PMID- 19740080
TI  - The response to short-term intensive insulin therapy in type 2 diabetes.
AB  - AIM: Although a short course of intensive insulin therapy (IIT) can improve beta
      cell function and glycaemic control in most patients with newly diagnosed type 2
      diabetes (T2DM), the impact of this intervention in diabetes of longer duration
      has not been carefully studied. Thus, we sought to evaluate the effect of short
      term IIT in patients with established T2DM. METHODS: Thirty-four patients, with
      diabetes of mean 5.9 +/- 6.6 years duration, underwent 4-8 weeks of IIT, with 4-h
      meal test administered at baseline and at 1 day post-IIT. A positive clinical
      response was defined as fasting glucose < 7.0 mmol/l off any antidiabetic therapy
      at the latter test. RESULTS: A positive response was achieved in 68% (n = 23) of
      the subjects. At baseline meal test, the responders had lower glucose levels than
      the non-responders from 120 to 240 min (all timepoints p < or = 0.0008) and
      higher late incremental area-under-the-C-peptide-curve (AUC(Cpep)), particularly
      from 60 to 150 min (all p < 0.005). Beta-cell function (ratio of AUC(Cpep) to
      AUC(gluc) divided by HOMA-IR) was similar between the groups at baseline (median
      54.1 vs. 51.3, p = 0.62) but after IIT was significantly higher in the responders
      (109.3 vs. 57.4, p = 0.009). At baseline, the strongest predictors of the change
      in beta-cell function were glucose levels between 180 and 240 min (all r = -0.5,
      p = 0.005) and incremental AUC(Cpep) from 120 to 180 min (all r > or = 0.66, p <
      or = 0.0001), both reflecting late-phase insulin secretion. CONCLUSIONS: The
      clinical response to short-term IIT is variable, consistent with the
      heterogeneity of T2DM. However, preserved late-phase insulin secretion may
      identify those patients who can benefit from this intervention with improved beta
      cell function.

PMID- 19740081
TI  - Dietary supplementation of tetradecylthioacetic acid increases feed intake but
      reduces body weight gain and adipose depot sizes in rats fed on high-fat diets.
AB  - AIM: The pan-peroxisome proliferator-activated receptor (PPAR) ligand and fatty
      acid analogue tetradecylthioacetic acid (TTA) may reduce plasma lipids and
      enhance hepatic lipid metabolism, as well as reduce adipose tissue sizes in rats
      fed on high-fat diets. This study further explores the effects of TTA on weight
      gain, feed intake and adipose tissue functions in rats that are fed a high-fat
      diet for 7 weeks. METHODS: The effects on feed intake and body weight during 7
      weeks' dietary supplement with TTA ( approximately 200 mg/kg bw) were studied in
      male Wistar rats fed on a lard-based diet containing approximately 40% energy
      from fat. Adipose tissue mass, body composition and expression of relevant genes
      in fat depots and liver were measured at the end of the feeding. RESULTS: Despite
      higher feed intake during the final 2 weeks of the study, rats fed on TTA gained
      less body weight than lard-fed rats and had markedly decreased subcutaneous,
      epididymal, perirenal and mesenteric adipose depots. The effects of TTA feeding
      with reduced body weight gain and energy efficiency (weight gain/feed intake)
      started between day 10 and 13. Body contents of fat, protein and water were
      reduced after feeding lard plus TTA, with a stronger decrease in fat relative to
      protein. Plasma lipids, including Non-Esterified Fatty Acids (NEFA), were
      significantly reduced, whereas fatty acid beta-oxidation in liver and heart was
      enhanced in lard plus TTA-fed rats. Hepatic UCP3 was expressed ectopically both
      at protein and mRNA level (>1900-fold), whereas Ucp1 mRNA was increased
      approximately 30-fold in epididymal and approximately 90-fold in mesenteric fat
      after lard plus TTA feeding. CONCLUSION: Our data support the hypothesis that TTA
      feeding may increase hepatic fatty acid beta-oxidation, and thereby reduce the
      size of adipose tissues. The functional importance of ectopic hepatic UCP3 is
      unknown, but might be associated with enhanced energy expenditure and thus the
      reduced feed efficiency.

PMID- 19740082
TI  - A reduction in severe hypoglycaemia in type 1 diabetes in a randomized crossover
      study of continuous intraperitoneal compared with subcutaneous insulin infusion.
AB  - AIM: Continuous intraperitoneal insulin infusion (CIPII) with the DiaPort system
      using regular insulin was compared to continuous subcutaneous insulin infusion
      (CSII) using insulin Lispro, to investigate the frequency of hypoglycemia, blood
      glucose control, quality of life, and safety. METHODS: In this open, randomized,
      controlled, cross-over, multinational, 12-month study, 60 type 1 diabetic
      patients with frequent hypoglycemia and/or HbA1c > 7.0% with CSII were randomized
      to CIPII or CSII. The aim was to obtain the best possible blood glucose while
      avoiding hypoglycemia. RESULTS: The frequency of any hypoglycemia was similar
      (CIPII 118.2 (SD 82.6) events / patient year, CSII 115.8 (SD 75.7) p = 0.910).
      The incidence of severe hypoglycemia with CSII was more than twice the one with
      CIPII (CIPII 34.8 events / 100 patient years, CSII 86.1, p = 0.013). HbA1c, mean
      blood glucose, and glucose fluctuations were not statistically different.
      Treatment-related severe complications occurred mainly during CIPII: port
      infections (0.47 events / patient year), abdominal pain (0.21 events / patient
      year), insulin underdelivery (0.14 events / patient year). Weight gain was
      greater with CSII (+ 1.5 kg vs. - 0.1 kg, p = 0.013), quality of life better with
      CIPII. CONCLUSIONS: In type 1 diabetes CIPII with DiaPort reduces the number of
      severe episodes of hypoglycemia and improves quality of life with no weight gain.
      Because of complications, indications for CIPII must be strictly controlled.
      CIPII with DiaPort is an alternative therapy when CSII is not fully successful
      and provides an easy method of intraperitoneal therapy.

PMID- 19740083
TI  - Interaction of beta-blockers with the renal uptake transporter OCT2.
AB  - AIM: The uptake of drugs from the blood into the renal tubular cells is a key
      determinant for renal secretion and may influence their systemic plasma
      concentrations and extrarenal effects. Metformin, used for treatment of type 2
      diabetes, is taken up into renal tubular cells by the organic cation transporter
      2 (OCT2). Because many patients with type 2 diabetes receiving metformin are
      concomitantly treated with beta-blockers, we tested whether beta-blockers can
      inhibit OCT2-mediated drug transport. METHOD: Using Madin-Darby canine kidney II
      cells stably expressing the uptake transporter OCT2, we analysed whether the beta
      blockers bisoprolol, carvedilol, metoprolol and propranolol inhibit the transport
      of OCT2 substrates 1-methyl-4-phenylpyridinium (MPP(+)) and metformin. RESULTS:
      Neither bisoprolol nor metoprolol significantly inhibited the uptake of MPP(+),
      whereas a significant inhibition was observed for carvedilol und propranolol
      (half maximal inhibitory concentration IC(50): 26.3 and 67.5 microM)
      respectively. Moreover, all beta-blockers significantly inhibited OCT2-mediated
      metformin uptake (IC(50) for bisoprolol: 2.4 microM, IC(50) for carvedilol: 2.3
      microM, IC(50) for metoprolol: 50.2 microM and IC(50) for propranolol: 8.3
      microM). CONCLUSION: These in vitro results demonstrate that alterations of
      uptake transporter function by beta-blockers have to be considered as potential
      mechanisms underlying drug-drug interactions in the kidney.

PMID- 19740084
TI  - Comment on: Tattooing of skin results in transportation and light-induced
      decomposition of tattoo pigments.
AB  - Decorative tattoos have become a common feature of many societies. Their
      popularity appears mainly driven by fashion, and scant attention has been paid to
      any associated risk. The risks can be associated either with the tattooees'
      proclivity for risk taking in general, or with the substances used in the
      tattoos. It is well established that tattoo pigments wander widely in the body
      after they have been injected, and research now suggests that azo pigments may
      become mutagenic after exposure to either natural light or laser light. This may
      not only affect the risk profile of tattoos themselves, but also tattoo removal
      using lasers.

PMID- 19740085
TI  - Is elevated noradrenaline an aetiological factor in a number of diseases?
AB  - 1 Here I put forth the hypothesis that noradrenaline (NA), which is a signalling
      molecule in the brain and sympathetic nervous system (SNS), is an aetiological
      factor in a number of diseases. 2 In a previous paper (Fitzgerald, Int. J.
      Cancer, 124, 2009, 257), I examined evidence that elevated NA is a factor in
      various types of cancer. Here I extend the argument to several other diseases,
      including diabetes mellitus, open-angle glaucoma, osteoarthritis and rheumatoid
      arthritis and asthma. 3 The principal hypothesis is that, largely as a result of
      genetics, elevated noradrenergic tone in the SNS predisposes a large number of
      individuals to a broad range of diseases. 4 For each of the above five diseases,
      I briefly examine the following four lines of evidence to assess the hypothesis:
      i) whether pharmacological studies in rodents that manipulate NA levels or
      receptors affect these diseases; ii) whether pharmacological manipulation of NA
      in humans affects these diseases; iii) whether bipolar disorder, excessive body
      weight, and hypertension, which may all three involve elevated NA, tend to be
      comorbid with these diseases and iv) whether psychological stressors tend to
      cause or exacerbate these conditions, since psychological stress is associated
      with increased release of NA. 5 The four lines of evidence tend to support the
      hypothesis.

PMID- 19740086
TI  - Evidence that endogenous inosine and adenosine-mediated hyperglycaemia during
      ischaemia-reperfusion through A3 adenosine receptors.
AB  - 1 The molecular mechanism underlying stress-induced hyperglycemia has not been
      comprehensively clarified. Recently, we demonstrated in ischaemia-reperfusion (I
      R) stress-subjected liver that inosine and adenosine are mainly responsible for
      the hyperglycemia observed. 2 We aimed to advance in the knowledge of the role of
      inosine plus adenosine as mediators of hepatic-induced hyperglycemia detected
      after I-R in lower limbs. 3 Acute ischaemia was conducted in anesthetized rats by
      occluding downstream abdominal aorta and cava vein; then, reperfusion was
      allowed. Blood samples from hepatic or abdominal cava veins were taken throughout
      the experiments to measure glucose, inosine and adenosine. Antagonists to
      adenosine (AdoR) and adrenergic receptors (AdrR) were administered during
      ischaemia to analyze their effect on hepatic glucose release. 4 Ischaemia up to
      60 min produced minor increase of glucose and nucleosides blood values, but 5 min
      of ischaemia followed by 2- (or 10-) min reperfusion increased glucose 23%, and
      those of inosine or adenosine by 100%. After 60 min of ischaemia and 10 min of
      reperfusion, glycemia rose 2-fold and blood inosine and adenosine, 3.3- and 2.7
      fold, respectively. A linear positive correlation, r(2), as high as 0.839 between
      glucose and either nucleoside blood values was calculated. The hyperglycemia
      response to I-R decreased by 0, 25, 33, 45 and 100% after selective inhibition of
      A(2B) AdoR, A(2A) AdoR, a(1B) AdrR, A(1) AdoR, and A(3) AdoR, respectively. 5
      Inosine-adenosine couple through activation of hepatic A(3) AdoR is the main
      signal for releasing glucose from liver glycogen and for promoting hyperglycemia
      following experimental injury of I-R from lower limbs.

PMID- 19740087
TI  - Nuclear expression of mu-opioid receptors in a human mesothelial cell line.
AB  - 1 Possibly acting via mu-opioid receptors (MORs), morphine inhibits the formation
      of experimentally induced postoperative abdominal adhesions in rats. Mesothelial
      cells may participate in adhesion formation by secreting mediators that interfere
      negatively with fibrinolysis. Morphine may prevent adhesions by inhibiting the
      release of pro-adhesion mediators from mesothelial cells. This study aimed to
      investigate whether human mesothelial cells express MOR-1; if so, such could
      constitute a site of action for morphine in adhesion prevention. 2 Cells from Met
      5A, a human mesothelial cell line were seeded and prepared for
      immunocytochemistry and Western blotting. 3 Immunocytochemistry showed MOR-1
      expression in mesothelial cells, predominantly in the nuclei. Western blotting
      showed two bands (c. 35 and 50 kDa) which correspond to those obtained with a
      control lysate from cells known to express MORs. In addition, we found MOR-1
      expression with nuclear and cytoplasmatic localization in biopsies from human
      abdominal adhesions. 4 The current findings may suggest that morphine could
      interact directly with mesothelial cells via MOR-1 receptors, and thereby
      modulate adhesion formation, possibly by interfering with the release of pro
      adhesion factors from these cells.

PMID- 19740088
TI  - Interaction between renin-angiotensin and sympathetic nervous systems in a rat
      model of pressure overload cardiac hypertrophy.
AB  - 1 A raised cardiac workload activates neurohormones which will increase muscle
      mass and shift contractility to the right along the Frank-Starling curve. 2 This
      study examined the interaction between the SNS and RAS in contributing to
      vascular responsiveness following the development of cardiac hypertrophy due to
      aortic banding. 3 Sprague Dawley rats (180-200 g) were assigned to one of six
      groups; Normal, Sham-operated, Aortic Banded (AB), Aortic Banded treated with
      losartan (ABLOS), Aortic Banded treated with 6-hydroxydopamine (ABSYMP) and
      Aortic banded treated with both losartan and 6-hydroxydopamine (ABSYMPLOS). A
      constricting band was placed around the supra renal aorta on day zero with drug
      treatment from day 37 to day 44. Vasopressor responses to noradrenaline,
      phenylephrine, methoxamine and angiotensin II were measured on day 45. 4 The
      magnitudes of the MAP responses to all vasoactive agents, expressed as percentage
      changes, were similar in Normal and Sham groups, but reduced in the AB group.
      ABLOS group showed attenuated response to ANGII whereas all responses were
      enhanced in the ABSYM group. 5 A positive interaction between the two systems was
      observed with alpha(1A)-adrenoceptors identified as a major component of SNS and
      AT(1) receptors of RAS to induce vasopressor effects.

PMID- 19740089
TI  - Deliberation before determination: the definition and evaluation of good decision
      making.
AB  - OBJECTIVES: In this article, we examine definitions of suggested approaches to
      measure the concept of good decisions, highlight the ways in which they converge,
      and explain why we have concerns about their emphasis on post-hoc estimations and
      post-decisional outcomes, their prescriptive concept of knowledge, and their lack
      of distinction between the process of deliberation, and the act of decision
      determination. BACKGROUND: There has been a steady trend to involve patients in
      decision making tasks in clinical practice, part of a shift away from paternalism
      towards the concept of informed choice. An increased understanding of the
      uncertainties that exist in medicine, arising from a weak evidence base and, in
      addition, the stochastic nature of outcomes at the individual level, have
      contributed to shifting the responsibility for decision making from physicians to
      patients. This led to increasing use of decision support and communication
      methods, with the ultimate aim of improving decision making by patients. Interest
      has therefore developed in attempting to define good decision making and in the
      development of measurement approaches. METHOD: We pose and reflect whether
      decisions can be judged good or not, and, if so, how this goodness might be
      evaluated. RESULTS: We hypothesize that decisions cannot be measured by reference
      to their outcomes and offer an alternative means of assessment, which emphasizes
      the deliberation process rather than the decision's end results. We propose
      decision making comprises a pre-decisional process and an act of decision
      determination and consider how this model of decision making serves to develop a
      new approach to evaluating what constitutes a good decision making process. We
      proceed to offer an alternative, which parses decisions into the pre-decisional
      deliberation process, the act of determination and post-decisional outcomes.
      DISCUSSION: Evaluating the deliberation process, we propose, should comprise of a
      subjective sufficiency of knowledge, as well as emotional processing and
      affective forecasting of the alternatives. This should form the basis for a good
      act of determination.

PMID- 19740090
TI  - The effect of mGlu8 deficiency in animal models of psychiatric diseases.
AB  - The metabotropic glutamate receptor subtype 8 (mGlu(8)) is presynaptically
      located and regulates the release of the transmitter. Dysfunctions of this
      mechanism are involved in the pathophysiology of different psychiatric disorders.
      mGlu(8) deficient mice have been previously investigated in a range of studies,
      but the results are contradictory and there are still many open questions.
      Therefore, we tested mGlu(8)-deficient animals in different behavioral tasks that
      are commonly used in neuropsychiatric research. Our results show a robust
      contextual fear deficit in mGlu(8)-deficient mice. Furthermore, novel object
      recognition, chlordiazepoxide-facilitated extinction of operant conditioning and
      the acoustic startle response were attenuated by mGlu(8) deficiency. We found no
      changes in sensory processing, locomotor activity, prepulse inhibition,
      phencyclidine-induced changes in locomotion or prepulse inhibition, operant
      conditioning, conditioned fear to a discrete cue or in animal models of innate
      fear and post-traumatic stress disorder. We conclude that mGlu(8) might be a
      potential target for disorders with pathophysiological changes in brain areas
      where mGlu(8) modulates glutamate and gamma-amino butyric acid (GABA)
      transmission. Our data especially point to anxiety disorders involving
      exaggerated contextual fear, such as generalized anxiety disorders, and to
      conditions with disturbed declarative memory.

PMID- 19740091
TI  - Postnatal handling reverses social anxiety in serotonin receptor 1A knockout
      mice.
AB  - Mice lacking the serotonin receptor 1A (Htr1a knockout, Htr1a(KO)) show increased
      innate and conditioned anxiety. This phenotype depends on functional receptor
      activity during the third through fifth weeks of life and thus appears to be the
      result of long-term changes in brain function as a consequence of an early
      deficit in serotonin signaling. To evaluate whether this phenotype can be
      influenced by early environmental factors, we subjected Htr1a knockout mice to
      postnatal handling, a procedure known to reduce anxiety-like behavior and stress
      responses in adulthood. Offspring of heterozygous Htr1a knockout mice were
      separated from their mother and exposed 15 min each day from postnatal day 1
      (PD1) to PD14 to clean bedding. Control animals were left undisturbed. Maternal
      behavior was observed during the first 13 days of life. Adult male offspring were
      tested in the open field, social approach and resident-intruder tests and
      assessed for corticosterone response to restraint stress. Knockout mice showed
      increased anxiety in the open field and in the social approach test as well as an
      enhanced corticosterone response to stress. However, while no effect of postnatal
      handling was seen in wild-type mice, handling reduced anxiety-like behavior in
      the social interaction test and the corticosterone response to stress in knockout
      mice. These findings extend the anxiety phenotype of Htr1a(KO) mice to include
      social anxiety and demonstrate that this phenotype can be moderated by early
      environmental factors.

PMID- 19740092
TI  - Serotonin transporter deficiency in rats contributes to impaired object memory.
AB  - Serotonin is well known for its role in affection, but less known for its role in
      cognition. The serotonin transporter (SERT) has an essential role in serotonergic
      neurotransmission as it determines the magnitude and duration of the serotonin
      signal in the synaptic cleft. There is evidence to suggest that homozygous SERT
      knockout rats (SERT(-/-)), as well as humans with the short SERT allele, show
      stronger cognitive effects than wild-type control rats (SERT(+/+)) and humans
      with the long SERT allele after acute tryptophan depletion. In rats, SERT
      genotype is known to affect brain serotonin levels, with SERT(-/-) rats having
      lower intracellular basal serotonin levels than wild-type rats in several brain
      areas. In the present study, it was investigated whether SERT genotype affects
      memory performance in an object recognition task with different inter-trial
      intervals. SERT(-/-), heterozygous SERT knockout (SERT(+/-)) and SERT(+/+) rats
      were tested in an object recognition test applying an inter-trial interval of 2,
      4 and 8 h. SERT(-/-) and SERT(+/-) rats showed impaired object memory with an 8 h
      inter-trial interval, whereas SERT(+/+) rats showed intact object memory with
      this inter-trial interval. Although brain serotonin levels cannot fully explain
      the SERT genotype effect on object memory in rats, these results do indicate that
      serotonin is an important player in object memory in rats, and that lower
      intracellular serotonin levels lead to enhanced memory loss. Given its
      resemblance with the human SERT-linked polymorphic region and propensity to
      develop depression-like symptoms, our findings may contribute to further
      understanding of mechanisms underlying cognitive deficits in depression.

PMID- 19740093
TI  - Factor VIII gene (F8) mutations as predictors of outcome in immune tolerance
      induction of hemophilia A patients with high-responding inhibitors.
AB  - BACKGROUND: Immune tolerance induction (ITI) is the only therapeutic approach
      that can eradicate factor VIII (FVIII) inhibitors in patients with hemophilia A.
      Predictors of ITI outcome are still debated, and the role of F8 gene mutations in
      this is not well established. OBJECTIVES: To investigate the relationship between
      F8 genotype and ITI outcome in patients with severe hemophilia A and high
      responding inhibitors. PATIENTS AND METHODS: F8 mutations were identified in 86
      patients recruited as part of the Italian ITI registry (the PROFIT study). ITI
      outcome was centrally reviewed according to the following definitions: success
      (undetectable inhibitor and normal FVIII pharmacokinetics), partial success
      (inhibitor titer < 5 BU mL(-1) and/or abnormal FVIII pharmacokinetics), and
      failure. RESULTS: F8 mutations known to be associated with a high risk of
      inhibitor development (large deletions, inversions, nonsense mutations and splice
      site mutations) were found in 70 patients (81%); among these, the intron 22
      inversion was present in 49 patients (57%). In 16 patients (19%) lower-risk F8
      defects (small insertions/deletions and missense mutations) were identified. The
      latter group of patients showed a significantly higher ITI success rate than
      those carrying high-risk mutations [13/16 (81%) vs. 33/70 (47%); risk ratio 1.7,
      95% confidence interval (CI) 1.1-2.1, P = 0.01]. On multivariate analysis, the
      mutation risk class remained a significant predictor of success [adjusted odds
      ratio (OR) 6.2, 95% CI 1.1-36.0, P = 0.04], as were inhibitor titer at ITI start
      (< 5 BU mL(-1), OR 11.8, 95% CI 3.5-40.2, P < 0.001), and peak titer during ITI
      (< 100 BU mL(-1), OR 11.4, 95% CI 3.2-40.8, P < 0.001). CONCLUSIONS: ITI success
      is influenced by F8 genotype. This knowledge should contribute to the
      stratification of prognosis, and to the clinical choices made for ITI in patients
      with high-responding inhibitors.

PMID- 19740094
TI  - Platelet size distinguishes between inherited macrothrombocytopenias and immune
      thrombocytopenia.
AB  - BACKGROUND: Distinguishing inherited thrombocytopenias from immune
      thrombocytopenia (ITP) can be difficult, and patients are therefore at risk of
      misdiagnosis and inappropriate treatments. Although it is known that the most
      common inherited forms of thrombocytopenia are characterized by increased
      platelet size, the diagnostic power of this feature has never been investigated.
      OBJECTIVES: The aim of this study was to test the hypothesis that platelet size
      can be used to differentiate ITP from inherited macrothrombocytopenias.
      PATIENTS/METHODS: We measured mean platelet volume (MPV) and mean platelet
      diameter (MPD), within 2 h of blood sampling, in 35 patients with inherited
      macrothrombocytopenias [15 MYH9-related disease (MYH9-RD), three biallelic and 17
      monoallelic Bernard-Soulier syndrome (BSS)], and 56 with ITP. Using receiving
      operating characteristic analysis, we searched for the best cut-off values to
      differentiate between these conditions. RESULTS: As expected, platelets were
      larger in inherited macrothrombocytopenias than in ITP. An MPD larger than 3.3
      mum differentiated MYH9-RD and BSS from ITP with 0.89 sensitivity and 0.88
      specificity, and an MPV larger than 12.4 fL had 0.83 sensitivity and 0.89
      specificity. Combining MPD with MPV increased sensitivity and specificity to 0.97
      and 0.89, respectively. CONCLUSION: Platelet size evaluation by both an
      appropriate cell counter and blood film examination is useful for differentiating
      inherited macrothrombocytopenias from ITP.

PMID- 19740095
TI  - Platelet tetraspanins: small but interesting.

PMID- 19740096
TI  - A platelet tetraspanin superfamily member, CD151, is required for regulation of
      thrombus growth and stability in vivo.
AB  - BACKGROUND: This study was designed to determine the role of CD151 in platelet
      thrombus formation in vivo and define the contribution of platelet vs.
      endothelial CD151 in regulating platelet thrombus formation in vivo. METHODS AND
      RESULTS: Using intravital microscopy and ferric chloride (FeCl(3)) injury of
      mesenteric arterioles, we found that thrombi formed in CD151(+/-) and CD151(-/-)
      mice were smaller and less stable, than those formed in CD151(+/+) mice, with a
      tendency for embolization. Similarly, in Folt's FeCl(3)-induced carotid injury
      model, both CD151(+/-) and CD151(-/-) mice showed more prolonged times to 95%
      vessel occlusion than CD151(+/+) mice. In addition, laser-induced injury of
      cremaster muscle arterioles showed that thrombi formed in CD151(+/-) and CD151(-/
      ) mice were smaller and less stable than those formed in CD151(+/+) mice.
      Following platelet depletion/reconstitution with ex vivo-labeled donor platelets,
      platelet-depleted CD151(+/+) mice that received reconstitution with CD151(-/-)
      platelets had smaller thrombi that were unstable and embolized. In contrast,
      platelet-depleted CD151(-/-) mice that received reconstitution with CD151(+/+)
      platelets had normal thrombi that were stable. CONCLUSIONS: These data provide
      evidence that platelet CD151 is required for regulating thrombus formation in
      vivo.

PMID- 19740097
TI  - Bacteria-platelet interactions.

PMID- 19740099
TI  - Variation in anticoagulant composition regulates differential effects of
      prothrombin complex concentrates on thrombin generation.

PMID- 19740098
TI  - Genetics of platelet reactivity in normal, healthy individuals.
AB  - BACKGROUND: The Platelet Function Analyzer-100 (PFA-100) is widely used to
      measure platelet reactivity in whole blood under high shear. OBJECTIVE: To
      characterize the genetic component of platelet reactivity among normal
      individuals, using the PFA-100. METHODS: We compared baseline platelet reactivity
      with sex, age, platelet count, hematocrit, plasma von Willebrand factor antigen
      (VWF:Ag), and alleles of seven candidate genes: integrin subunits alpha2 (ITGA2)
      and beta3 (ITGB3), platelet glycoproteins GPIbalpha (GP1BA) and GPVI (GP6),
      purinogenic receptors (P2RY1 and P2RY12) and cyclooxygenase-1 (COX1). RESULTS:
      Based on linear and logistic regression models, we report an inverse correlation
      between baseline closure time (CT) initiated by collagen plus epinephrine (CEPI)
      and plasma VWF:Ag level, ITGA2 807T and P2RY1 893C, and an inverse correlation
      between baseline CT initiated by collagen plus adenosine diphosphate (CADP) and
      P2RY1 893C or GP1BA -5C. CONCLUSIONS: These results indicate that genetic
      polymorphisms in ITGA2 and P2RY1 combine with plasma VWF:Ag levels to modulate
      baseline platelet reactivity in response to collagen plus EPI, while genetic
      differences in P2RY1 and GP1BA significantly effect platelet responses to
      collagen plus ADP. Our results demonstrate that the PFA-100 can be used to
      evaluate the effects of genetic predictors of platelet function.

PMID- 19740100
TI  - Studies of mice lacking the GPIb-V-IX complex question the role of this receptor
      in atherosclerosis.

PMID- 19740101
TI  - Insulin-like growth factor-1 protects from vascular stenosis and accelerates re
      endothelialization in a rat model of carotid artery injury.
AB  - BACKGROUND: IGF-1 is a potent mitogen for vascular smooth muscle cells, but
      exerts protective effects on endothelial cells that may trigger antiatherogenic
      mechanisms. OBJECTIVES: This study was designed to test the hypothesis that an
      IGF-1 excess following arterial injury prevents neointima formation and vascular
      stenosis. METHODS: Rats were subjected to carotid balloon injury and treated with
      IGF-1 (1.2 mg kg(-1) per die) or saline for 10 days. RESULTS: In IGF-1 treated
      animals, high tissue levels of eNOS, Akt and its phosphorylated form were found,
      confirming activation of IGF-1-dependent signaling pathways. IGF-1 markedly
      reduced neointima formation and post-injury arterial stenosis. IGF-1 exerted
      proliferative and anti-apoptotic effects in the media of injured carotids, but
      inhibited mitotic activity and induced apoptosis in the neointima. Furthermore,
      IGF-1 stimulated mobilization of progenitor endothelial cells and re
      endothelialization of the injured arteries. L-NAME administration inhibited IGF-1
      vasculoprotective effects. CONCLUSIONS: IGF-1 attenuates post-injury carotid
      stenosis by exerting differential effects in the neointima and tunica media with
      regard to the key components of the response to injury. The data point to a novel
      role of IGF-1 as a potent vasculoprotective factor.

PMID- 19740103
TI  - Interferon-gamma bolsters CD95/Fas-mediated apoptosis of astroglioma cells.
AB  - In the present study, we investigated the mechanisms of the resistance to CD95
      mediated cell death and the effects of interferon-gamma in modulating the
      susceptibility to CD95-induced apoptosis of human astroglioma cells. We found
      that interferon-gamma administration sensitized cancer cells to CD95-mediated
      apoptosis. The mechanism underlying this sensitization appeared to be associated
      with a framework of cell changes, including up-regulation of death receptor at
      the cell surface, pro-apoptotic molecule Bax and Bak over-expression and
      mitochondria hyperpolarization, as is known to be associated with cell
      sensitization to apoptosis. An involvement of the proteasome activity in the
      mechanism of sensitization by interferon-gamma was also detected, probably as a
      result of the differing expression of catalytic proteasome subunits. Taken
      together, these findings suggest that interferon-gamma could represent a
      promising candidate for modulating astroglioma cell apoptotic susceptibility.

PMID- 19740102
TI  - Endothelial cell specific adhesion molecule (ESAM) localizes to platelet-platelet
      contacts and regulates thrombus formation in vivo.
AB  - BACKGROUND: In resting platelets, endothelial cell specific adhesion molecule
      (ESAM) is located in alpha granules, increasing its cell surface expression
      following platelet activation. However, the function of ESAM on platelets is
      unknown. OBJECTIVE: To determine whether ESAM has a role in thrombus formation.
      METHODS AND RESULTS: We found that following platelet activation ESAM localizes
      to the junctions between adjacent platelets, suggesting a role for this protein
      in contact-dependent events that regulate thrombus formation. To test this
      hypothesis we examined the effect of ESAM deletion on platelet function. In vivo,
      ESAM(-/-) mice achieved more stable hemostasis than wild-type mice following tail
      transection, and developed larger thrombi following laser injury of cremaster
      muscle arterioles. In vitro, ESAM(-/-) platelets aggregated at lower
      concentrations of G protein-dependent agonists than wild-type platelets, and were
      more resistant to disaggregation. In contrast, agonist-induced calcium
      mobilization, alpha(IIb)beta(3) activation, alpha-granule secretion and platelet
      spreading, were normal in ESAM-deficient platelets. To understand the molecular
      mechanism by which ESAM regulates platelet activity, we utilized a PDZ domain
      array to identify the scaffold protein NHERF-1 as an ESAM binding protein, and
      further demonstrated that it associates with ESAM in both resting and activated
      platelets. CONCLUSIONS: These findings support a model in which ESAM localizes to
      platelet contacts following platelet activation in order to limit thrombus growth
      and stability so that the optimal hemostatic response occurs following vascular
      injury.

PMID- 19740105
TI  - A moss pentatricopeptide repeat protein binds to the 3' end of plastid clpP pre
      mRNA and assists with mRNA maturation.
AB  - Pentatricopeptide repeat (PPR) proteins constitute a large family in land plants
      and are required for various post-transcriptional steps associated with RNA in
      plant organelles. The moss Physcomitrella patens PPR protein, PpPPR_38, is a
      nuclear-encoded chloroplast protein and was previously shown to be involved in
      the maturation step of chloroplast clpP pre-mRNA. To understand precisely the
      molecular function of PpPPR_38, we prepared recombinant PpPPR_38 protein and
      characterized it in maturation steps of clpP pre-mRNA. In vitro RNA-binding
      assays showed that the recombinant protein strongly bound to the clpP-5'-rps12
      intergenic region, which is highly AU-rich and includes an inverted repeat
      sequence potentially forming a stem-loop structure. Digestion of the bound RNA
      region by RNase V1 was significantly accelerated by the addition of the
      recombinant protein. This strongly suggests that the binding of PpPPR_38
      facilitates the formation of a stable stem-loop structure. An in vitro
      degradation assay using chloroplast lysates gave rise to the possibility that the
      stable stem-loop structure formed by PpPPR_38 contributes the correct intergenic
      RNA cleavage and protection of mature clpP mRNA against 3' to 5' exoribonuclease.
      Because an RNA-binding assay also showed weak binding to the clpP first exon
      intron region, PpPPR_38 is likely to be related to the splicing of clpP pre-mRNA.
      Taking together all of the above findings, we conclude that PpPPR_38 is necessary
      for several steps in the clpP mRNA maturation process.

PMID- 19740104
TI  - Mutational analysis of the preferential binding of human topoisomerase I to
      supercoiled DNA.
AB  - Human topoisomerase I binds DNA in a topology-dependent fashion with a strong
      preference for supercoiled DNAs of either sign over relaxed circular DNA. One
      hypothesis to account for this preference is that a second DNA-binding site
      exists on the enzyme that mediates an association with the nodes present in
      supercoiled DNA. The failure of the enzyme to dimerize, even in the presence of
      DNA, appears to rule out the hypothesis that two binding sites are generated by
      dimerization of the protein. A series of mutant protein constructs was generated
      to test the hypotheses that the homeodomain-like core subdomain II (residues 233
      319) provides a second DNA-binding site, or that the linker or basic residues in
      core subdomain III are involved in the preferential binding to supercoiled DNAs.
      When putative DNA contact points within core subdomain II were altered or the
      domain was removed altogether, there was no effect on the ability of the enzyme
      to recognize supercoiled DNA, as measured by both a gel shift assay and a
      competition binding assay. However, the preference for supercoils was noticeably
      reduced for a form of the enzyme lacking the coiled-coil linker region or when
      pairs of lysines were changed to glutamic acids in core subdomain III. The
      results obtained implicate the linker and solvent-exposed basic residues in core
      subdomain III in the preferential binding of human topoisomerase I to supercoiled
      DNA.

PMID- 19740106
TI  - Analysis of the region for receptor binding and triggering of oligomerization on
      Bacillus thuringiensis Cry1Aa toxin.
AB  - The determination of the receptor-binding region of Cry toxins produced by
      Bacillus thuringiensis is expected to facilitate an improvement in their
      insecticidal ability through protein engineering. We analyzed the region on
      Cry1Aa molecules involved in interactions with the cadherin-like protein receptor
      BtR175 using cysteine-substituted mutant toxins and several synthetic peptides
      corresponding to the loops in domain 2. In addition, the region necessary to
      trigger oligomerization was analyzed using these mutant toxins. The mutant toxins
      were modified by two types of molecule, i.e. digested fragments of the Cry1Aa
      precursor with an average molecular mass of 2 kDa and 5-iodoacetamidofluorescein,
      which has a molecular mass of 515 kDa. We examined whether these modifications
      interfere with the toxin-BtR175 interaction as a result of steric hindrance. 5
      Iodoacetamidofluorescein modification of R311C, N376C and G442C revealed steric
      hindrance effects, indicating that R311 on loop 1, N376 on loop 2 and G442 on
      loop 3 are on the contact face of the toxin-BtR175 interface when Cry1Aa binds to
      BtR175. Loop 2 is thought to interact with BtR175 directly, as a peptide
      corresponding to the N-terminal half of loop 2, (365)LYRRIILG(372), has the
      potential to bind to BtR175 fragments. Meanwhile, mutant toxins with cysteine
      substitutions in loops 1 and 2 were oligomerized by the binding of digested
      fragments in the activation process without receptor interaction, and the wild
      type toxin formed oligomers by interaction with BtR175 fragments. These
      observations suggest that loops 1 and 2 form both a binding region and a sensor
      region, which triggers toxin oligomer formation. Structured digital abstract: *
      MINT-7259673, MINT-7259722, MINT-7259737, MINT-7259757, MINT-7259774, MINT
      7259791, MINT-7259808, MINT-7259685, MINT-7259707, MINT-7259830: btr175
      (uniprotkb:Q9XY09) binds (MI:0407) to cry1Aa (uniprotkb:P0A366) by surface
      plasmon resonance (MI:0107).

PMID- 19740107
TI  - Epidermal growth factor receptor ligands as new extracellular targets for the
      metastasis-promoting S100A4 protein.
AB  - The function of S100A4, a member of the calcium-binding S100 protein family, has
      been associated with tumor invasion and metastasis. Although an essential pro
      metastatic role of extracellular S100A4 in tumor progression has been
      demonstrated, the identification of the precise underlying mechanisms and protein
      partners (receptors) has remained elusive. To identify putative targets for
      extracellular S100A4, we screened a phage display peptide library using S100A4 as
      bait. We identified three independent peptide motifs with varying affinities for
      the S100A4 protein. Sequence analyses indicated that the most abundant peptide
      mimicked the F/YCC motif present in the epidermal growth factor domain of ErbB
      receptor ligands. S100A4 selectively interacted with a number of epidermal growth
      factor receptor (EGFR) ligands, demonstrating highest affinity for amphiregulin.
      Importantly, we found that S100A4 stimulated EGFR/ErbB2 receptor signaling and
      enhanced the amphiregulin-mediated proliferation of mouse embryonic fibroblasts.
      S100A4-neutralizing antibodies, as well as EGFR- and ErbB2 receptor-specific
      tyrosine kinase inhibitors, blocked these effects. The present results suggest
      that extracellular S100A4 regulates tumor progression by interacting with EGFR
      ligands, thereby enhancing EGFR/ErbB2 receptor signaling and cell proliferation.
      Structured digital abstract: * MINT-7256556: EGF (uniprotkb:P01133) binds
      (MI:0407) to S100A4 (uniprotkb:P26447) by far western blotting (MI:0047) * MINT
      7256512: BC (uniprotkb:P35070) binds (MI:0407) to S100A4 (uniprotkb:P26447) by
      far western blotting (MI:0047) * MINT-7256485, MINT-7256618, MINT-7256636: AR
      (uniprotkb:P15514) binds (MI:0407) to S100A4 (uniprotkb:P26447) by far western
      blotting (MI:0047) * MINT-7256494: HB-EGF (uniprotkb:Q99075) binds (MI:0407) to
      S100A4 (uniprotkb:P26447) by far western blotting (MI:0047) * MINT-7256502: P53
      (uniprotkb:P04637) binds (MI:0407) to S100A4 (uniprotkb:P26447) by far western
      blotting (MI:0047) * MINT-7256654: S100A2 (uniprotkb:P29034) binds (MI:0407) to
      AR (uniprotkb:P15514) by far western blotting (MI:0047) * MINT-7256693: S100A5
      (uniprotkb:P33763) binds (MI:0407) to AR (uniprotkb:P15514) by far western
      blotting (MI:0047) * MINT-7256593: S100A4 (uniprotkb:P26447) binds (MI:0407) to
      BC (uniprotkb:P35070) by pull down (MI:0096) * MINT-7256567: S100A4
      (uniprotkb:P26447) binds (MI:0407) to AR (uniprotkb:P15514) by pull down
      (MI:0096).

PMID- 19740108
TI  - Completing the hypusine pathway in Plasmodium.
AB  - In searching for new targets for antimalarials we investigated the biosynthesis
      of hypusine present in eukaryotic initiation factor-5A (eIF-5A) in Plasmodium.
      Here, we describe the cloning and expression of deoxyhypusine hydroxylase (DOHH),
      which completes the modification of eIF-5A through hydroxylation of
      deoxyhypusine. The dohh cDNA sequence revealed an ORF of 1236 bp encoding a
      protein of 412 amino acids with a calculated molecular mass of 46.45 kDa and an
      isoelectric point of 4.96. Interestingly, DOHH from Plasmodium has a FASTA SCORE
      of only 27 compared with its human ortholog and contains several matches similar
      to E-Z-type HEAT-like repeat proteins (IPR004155 (InterPro), PF03130 (Pfam),
      SM00567 (SMART) present in the phycocyanin lyase subunits of cyanobacteria.
      Purified DOHH protein displayed hydroxylase activity in a novel in vitro DOHH
      assay, but phycocyanin lyase activity was absent. dohh is present as a single
      copy gene and is transcribed in the asexual blood stages of the parasite. A
      signal peptide at the N-terminus might direct the protein to a different cellular
      compartment. During evolution, Plasmodium falciparum acquired an apicoplast that
      lost its photosynthetic function. It is possible that plasmodial DOHH arose from
      an E/F-type phycobilin lyase that gained a new role in hydroxylation. Structured
      digital abstract: * MINT-7255047: DHS (uniprotkb:P49366) enzymaticly reacts
      (MI:0414) with eIF-5A (uniprotkb:Q710D1) by enzymatic studies (MI:0415) * MINT
      7255326: DOHH (uniprotkb:Q8I701) enzymaticly reacts (MI:0414) with eIF-5A
      (uniprotkb:Q710D1) by enzymatic studies (MI:0415).

PMID- 19740109
TI  - Production of a recombinant mouse monoclonal antibody in transgenic silkworm
      cocoons.
AB  - In the present study, we describe the production of transgenic silkworms
      expressing a recombinant mouse mAb in their cocoons. Two transgenic lines, L- and
      H-, were generated that carried cDNAs encoding the L- and H-chains of a mouse IgG
      mAb, respectively, under the control of the enhancer-linked sericin-1 promoter.
      Cocoon protein analysis indicated that the IgG L- or H-chain was secreted into
      the cocoons of each line. We also produced a transgenic line designated L/H,
      which carried both cDNAs, by crossing the L- and H-lines. This line efficiently
      produced the recombinant mAb as a fully assembled H(2)L(2) tetramer in its
      cocoons, with negligible L- or H-chain monomer and H-chain dimer production.
      Thus, the H(2)L(2) tetramer was synthesized in, and secreted from, the middle
      silk gland cells. Crossing of the L/H-line with a transgenic line expressing a
      baculovirus-derived trans-activator produced a 2.4-fold increase in mAb
      expression. The recombinant mAb was extracted from the cocoons with a buffer
      containing 3 m urea and purified by protein G affinity column chromatography. The
      antigen-binding affinity of the purified recombinant mAb was identical to that of
      the native mAb produced by a hybridoma. Analysis of the structure of the N
      glycans attached to the recombinant mAb revealed that the mAb contained high
      mannose-, hybrid- and complex-type N-glycans. By contrast, insect-specific
      paucimannose-type glycans were not detected. Fucose residues alpha-1,3- and alpha
      1,6-linked to the core N-acetylglucosamine residue, both of which are found in
      insect N-glycans, were not observed in the N-glycans of the mAb.

PMID- 19740110
TI  - Purine nucleoside phosphorylases from hyperthermophilic Archaea require a CXC
      motif for stability and folding.
AB  - 5'-Deoxy-5'-methylthioadenosine phosphorylase II from Sulfolobus solfataricus
      (SsMTAPII) and purine nucleoside phosphorylase from Pyrococcus furiosus (PfPNP)
      are hyperthermophilic purine nucleoside phosphorylases stabilized by intrasubunit
      disulfide bonds. In their C-terminus, both enzymes harbour a CXC motif analogous
      to the CXXC motif present at the active site of eukaryotic protein disulfide
      isomerase. By monitoring the refolding of SsMTAPII, PfPNP and their mutants
      lacking the C-terminal cysteine pair after guanidine-induced unfolding, we
      demonstrated that the CXC motif is required for the folding of these enzymes.
      Moreover, two synthesized CXC-containing peptides with the same amino acid
      sequences present in the C-terminal regions of SsMTAPII and PfPNP were found to
      act as in vitro catalysts of oxidative folding. These small peptides are involved
      in the folding of partially refolded SsMTAPII, PfPNP and their CXC-lacking
      mutants, with a concomitant recovery of their catalytic activity, thus indicating
      that the CXC motif is necessary to obtain complete reversibility from the
      unfolded state of the two proteins. The two CXC-containing peptides are also able
      to reactivate scrambled RNaseA. The data obtained in the present study represent
      the first example of how the CXC motif improves both stability and folding in
      hyperthermophilic proteins with disulfide bonds.

PMID- 19740111
TI  - It's about time: the temporal dynamics of phenotypic selection in the wild.
AB  - Selection is a central process in nature. Although our understanding of the
      strength and form of selection has increased, a general understanding of the
      temporal dynamics of selection in nature is lacking. Here, we assembled a
      database of temporal replicates of selection from studies of wild populations to
      synthesize what we do (and do not) know about the temporal dynamics of selection.
      Our database contains 5519 estimates of selection from 89 studies, including
      estimates of both direct and indirect selection as well as linear and nonlinear
      selection. Morphological traits and studies focused on vertebrates were well
      represented, with other traits and taxonomic groups less well-represented.
      Overall, three major features characterize the temporal dynamics of selection.
      First, the strength of selection often varies considerably from year to year,
      although random sampling error of selection coefficients may impose bias in
      estimates of the magnitude of such variation. Second, changes in the direction of
      selection are frequent. Third, changes in the form of selection are likely
      common, but harder to quantify. Although few studies have identified causal
      mechanisms underlying temporal variation in the strength, direction and form of
      selection, variation in environmental conditions driven by climatic fluctuations
      appear to be common and important.

PMID- 19740112
TI  - Elasticity analysis in epidemiology: an application to tick-borne infections.
AB  - The application of projection matrices in population biology to plant and animal
      populations has a parallel in infectious disease ecology when next-generation
      matrices (NGMs) are used to characterize growth in numbers of infected hosts
      (R(0)). The NGM is appropriate for multi-host pathogens, where each matrix
      element represents the number of cases of one type of host arising from a single
      infected individual of another type. For projection matrices, calculations of the
      sensitivity and elasticity of the population growth rate to changes in the matrix
      elements has generated insight into plant and animal populations. These same
      perturbation analyses can be used for infectious disease systems. To illustrate
      this in detail we parameterized an NGM for seven tick-borne zoonoses and compared
      them in terms of the contributions to R(0) from three different routes of
      transmission between ticks, and between ticks and vertebrate hosts. The
      definition of host type may be the species of the host or the route of infection,
      or, as was the case for the set of tick-borne pathogens, a combination of species
      and the life stage at infection. This freedom means that there is a broad range
      of disease systems and questions for which the methodology is appropriate.

PMID- 19740113
TI  - Functional levels and nurse workload of elderly awaiting nursing home placement
      and nursing home residents: a comparative study.
AB  - The aim of this study was twofold: to compare the functional levels of elderly
      awaiting nursing home placement and nursing home residents, and to compare their
      nurses' physical and psychological workloads. In Norway, the demand for nursing
      home placement has increased greatly. Elderly awaiting placement can receive care
      from home health care services and/or from their families. Documenting elderly's
      functional levels may illuminate the extent of the carers' workloads and the need
      for support during the waiting period. The study was conducted in 2005 on two
      groups in northern Norway. Using the Multi-Dimensional Dementia Assessment Scale
      to assess functional levels, one group of nurses assessed elderly awaiting
      nursing home placement (n = 36) and another group of nurses assessed nursing home
      residents (n = 47). The nurses also reported physical and psychological workloads
      in caring for these elderly. A comparison of the functional levels between
      elderly awaiting nursing home placement and nursing home residents showed few
      statistically significant differences. Nursing home residents had two lower motor
      functions, needed more assistance with activities of daily living, more regular
      administration of enemas, were more often unable to speak, and showed lower
      orientation levels. Clinically significant similarities were found in five motor
      functions, including rising from lying to sitting, rising out of bed and walking,
      and in behavioural and psychiatric symptoms. Both groups of elderly had a high
      prevalence of sadness and fearfulness. The results of this study indicate that
      elderly awaiting nursing home placement can be as frail as nursing home
      residents. These results highlight the elderly's need for assistance and reveal
      the need for more nursing home beds. Nurses in home health care and nursing homes
      rated physical and psychological workloads similarly. As many carers provide care
      24 hours a day, these results also illuminate the need to support carers during
      the waiting period.

PMID- 19740114
TI  - The representation of healthcare end users' perspectives by surrogates in
      healthcare decisions: a literature review.
AB  - BACKGROUND: The representation of end users' perspectives in healthcare decisions
      requires involvement of their surrogates when the end users, i.e. certain
      patients, elderly people, children and people with disabilities, are unable to
      present their views. AIMS: To review critical issues, and the advantages and
      disadvantages of involving surrogates in representing end users' perspectives in
      healthcare decisions. METHODS: A systematic review of literature published in
      peer-reviewed journals from 1990 to 2005. RESULTS: Findings show that surrogates
      are used widely in health care and that they are necessary to represent end
      users' perspectives in healthcare decisions when the latter are unable to do so
      themselves. Critical issues in using surrogates include key ethical, social,
      cultural, legal and medico-technological factors; ascertaining the best interest
      of end users; potential conflict of interest; possible biased decisions and the
      burden on surrogates. The key advantage of surrogate involvement in healthcare
      decisions is their ability to represent end users' needs, values and wishes. The
      main disadvantages include potential discrepancies between the decisions and
      conclusions of surrogates and end users; the failure of surrogates to predict end
      users' preferences accurately and the lack of certainty that useful information
      will be obtained through the surrogacy process. CONCLUSION: This systematic
      review has revealed that the involvement of surrogates is an additional vital way
      to represent end users' perspectives in healthcare decisions where for a range of
      reasons their opinions are unable to be effectively ascertained. However, because
      of the heterogeneity of surrogates and end users, the selection of appropriate
      surrogates and deploying surrogate decisions require particularly careful
      consideration of their value in individual cases; thus, subsequent decision
      making must be reviewed on a case-to-case basis to seek to ensure that the best
      interests, needs and wishes of the end user are fully and accurately represented.

PMID- 19740115
TI  - A selective, high affinity 5-HT 2B receptor antagonist inhibits visceral
      hypersensitivity in rats.
AB  - BACKGROUND: RS-127445 is a selective, high affinity 5-HT(2B)receptor antagonist.
      We investigated whether 5-HT(2B)receptor antagonists can reduce colonic visceral
      hypersensitivity caused by restraint stress or by proximal colonic inflammation.
      METHODS: Visceral hypersensitivity was induced in rats by either restraint stress
      or injection of 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) into the proximal
      colon. Restraint stress produced a significant increase in numbers of abdominal
      contractions evoked by colorectal distension (CRD), measured as a quantitative
      index of visceral nociception in rats. Seven days after TNBS injection, the pain
      threshold to CRD at the non-inflamed distal colon, that was determined as the
      minimum pressure required to evoke abdominal cramp, was significantly decreased.
      The effect of RS-127445 on visceral hypersensitivity was assessed in either naive
      or TNBS-treated rats. KEY RESULTS: Oral administration of a selective, high
      affinity 5-HT(2B)receptor antagonist, RS-127445, significantly inhibited visceral
      hypersensitivity provoked by restraint stress (35 to 74% inhibition at 1 to 10 mg
      kg(-1)). Oral RS-127445 produced a significant suppression of TNBS-induced
      visceral hypersensitivity (15 to 62% inhibition at 3 to 30 mg kg(-1)), although
      it was without significant effect on the visceral nociceptive threshold of naive
      rats. RS-127445 (1 to 30 mg kg(-1), p.o.) also dose-dependently reduced the
      restraint stress-induced defecation in naive and TNBS-treated rats. CONCLUSIONS &
      INFERENCES: These results suggest that 5-HT(2B)receptors are involved in
      signaling from the colon in rats in which there is visceral hypersensitivity and
      that a selective 5-HT(2B)receptor antagonist could have therapeutic potential for
      the treatment of gut disorders characterized by visceral hypersensitivity.

PMID- 19740116
TI  - The effect of esomeprazole 20 mg twice daily on acoustic and perception
      parameters of the voice in laryngopharyngeal reflux.
AB  - BACKGROUND: Randomized, placebo-controlled studies have failed to demonstrate a
      significant treatment effect for laryngopharyngeal reflux (LPR) using traditional
      clinical endpoints. We compared the effect of esomeprazole 20 mg twice daily
      (b.i.d.) vs placebo on voice and acoustic-related measures in patients with LPR.
      METHODS: Patients with LPR underwent endoscopy and pH testing. Subsequently,
      patients underwent videostroboscopic recordings of the larynx, acoustic voice and
      speech analysis. A voice use and quality diary and oesophageal symptom diary were
      completed at baseline. Thereafter, patients were randomized to esomeprazole 20 mg
      twice daily vs placebo for 3 months. The voice use and quality diary and
      oesophageal symptom dairy were repeated during the last week of treatment.
      Videostroboscopy and acoustic voice and speech analysis were also performed at
      the end of treatment. KEY RESULTS: Twenty-four patients were randomized to the
      esomeprazole group and 17 to the placebo group. There was no significant
      difference in videostroboscopic reflux finding scores from baseline to post
      treatment. Acoustic measures also failed to demonstrate significant differences
      within the same or between groups, even when a sub-group analysis of patients
      with endoscopically documented oesophageal inflammation at baseline was
      performed. Additionally, no significant differences were found between groups
      when using voice use and quality diary. CONCLUSIONS & INFERENCES: Use of more
      specific laryngeal functional parameters such as voice-related acoustic measures
      of pitch range, fundamental frequency and intensity also failed to demonstrate a
      significant response to proton pump inhibitor treatment as compared to placebo in
      patients with suspected LPR.

PMID- 19740117
TI  - Proteinase-activated receptor-2 activation evokes oesophageal longitudinal smooth
      muscle contraction via a capsaicin-sensitive and neurokinin-2 receptor-dependent
      pathway.
AB  - BACKGROUND: Intraluminal acid evokes sustained oesophageal longitudinal smooth
      muscle (LSM) contraction and oesophageal shortening, which may play a role in
      oesophageal pain and the aetiology of hiatus hernia. In the opossum model, this
      reflex has been shown to involve mast cell activation and release of neurokinins
      from capsaicin-sensitive neurons. The aim of this study was to determine whether
      proteinase-activated receptor-2 (PAR-2) activation evokes reflex LSM contraction
      via similar mechanisms. METHODS: Tension recording studies were performed using
      opossum oesophageal LSM strips in the presence and absence of pharmacological
      agents. In addition, the effect of trypsin on single isolated LSM cells was
      determined using videomicroscopy, and the expression of PAR-2 in oesophageal
      tissue was examined using immunohistochemistry. KEY RESULTS: The PAR-2 agonist
      trypsin evoked sustained, concentration-dependent contraction of LSM muscle
      strips, but had no effect on isolated LSM cells. The trypsin-induced contraction
      was blocked by capsaicin desensitization, substance P (SP) desensitization or
      application of the selective neurokinin-2 (NK-2) receptor antagonist MEN 10376.
      Immunohistochemistry revealed co-localization of SP, calcitonin gene-related
      peptide and PAR-2 in axons of opossum oesophageal LSM. CONCLUSIONS & INFERENCES:
      Longitudinal smooth muscle contraction induced by trypsin involves capsaicin
      sensitive neurons and subsequent activation of NK-2, which is identical to the
      pathway involved in acid-induced LSM contraction and oesophageal shortening. This
      suggests that acid-induced LSM contraction may involve mast cell-derived
      mediators that activate capsaicin-sensitive neurons via PAR-2.

PMID- 19740118
TI  - The effects of hormonal contraceptives on bone turnover markers and bone health.
AB  - Sex hormones are important regulators of bone metabolism. As hormonal
      contraceptives contain either oestrogens or progestins, or a combination thereof,
      it is conceivable that these widely used agents have an effect on bone metabolism
      and bone health. The main users of hormonal contraceptives, adolescent girls and
      young women, are still building bone and accruing bone mass and may therefore be
      particularly susceptible to the effects of hormonal contraceptives on bone.
      Despite these concerns, the effects of hormonal contraceptives on bone health are
      still poorly understood. As biochemical markers of bone turnover have been proven
      useful tools in the assessment and monitoring of bone metabolism, we reviewed the
      effects of combined and gestagen-only hormonal contraceptives on bone turnover
      markers and related effects on bone mineral density and fracture risk in
      premenopausal women, as documented in the literature until January 2009.

PMID- 19740119
TI  - History of migraine with aura and cortical spreading depression from 1941 and
      onwards.
AB  - Several personal descriptions of migraine with aura from 1870 onwards reported a
      slow, gradual progression of symptoms. Lashley in 1941 meticulously chartered his
      own auras and concluded that the symptomatology reflected a cortical process
      progressing with a speed of 3 mm/min across the primary visual cortex. Leao
      described cortical spreading depression (CSD) in rabbits in 1944 and noticed its
      similarity to the migraine aura. Despite these scattered pieces of evidence, the
      prevailing theory was that the migraine aura was caused by a vasospasm and
      cortical ischaemia. The advent of a technique for measurements of regional
      cerebral blood flow (rCBF) in 1974 made it possible to detect spreading oligaemia
      during migraine aura. Between 1981 and 1990 a series of studies of rCBF during
      migraine attacks showed reduced brain blood flow posteriorly spreading slowly and
      contiguously anteriorly and crossing borders of supply of major cerebral
      arteries. These observations refuted the ischaemic hypothesis. The human studies
      showed initial hyperaemia followed by prolonged hypoperfusion. The relation
      between aura and CSD was known to cause short-lasting, and therefore not obvious
      vasodilation and it was considerably strengthened by the demonstration of a long
      lasting oligaemia in rats in the wake of CSD. In the primates CSD is not easily
      elicited, but it has in recent years been clearly demonstrated in patients with
      brain trauma and stroke. Finally, mutations for familial hemiplegic migraine have
      been expressed in mice and lower the threshold for CSD. The seminal papers on
      rCBF and CSD published in the 1980s caused a dramatic shift in our concepts of
      migraine aura. They moved attention from ischaemia to CSD and thereby to the
      brain itself, and paved the way for subsequent discoveries of brainstem
      mechanisms.

PMID- 19740120
TI  - Nitroglycerin provocation in normal subjects is not a useful human migraine
      model?
AB  - Provoking delayed migraine with nitroglycerin in migraine sufferers is a
      cumbersome model. Patients are difficult to recruit, migraine comes on late and
      variably and only 50-80% of patients develop an attack. A model using normal
      volunteers would be much more useful, but it should be validated by testing the
      response to drugs of known efficacy in acute migraine. Furthermore, treatment
      during headache rather than pretreatment is the most naturalist method. To fulfil
      these requirements we used continuous long-lasting infusion of glyceryl
      trinitrate (GTN) 0.2 microg kg-1 min-1 for 140 min and gave aspirin 1000 mg,
      zolmitriptan 5 mg or placebo to normal healthy volunteers. The design was double
      blind, placebo-controlled three-way crossover. Our hypothesis was that these
      drugs would be effective in the treatment of the mild constant headache induced
      by long-lasting GTN infusion. The headaches did not fulfil the International
      Headache Society diagnostic criteria for migraine without aura. Moreover, there
      was no effect on headache of either zolmitriptan or aspirin. Thus our hypothesis
      was disproved and we conclude that our model is not valid for the testing of new
      acute antimigraine drugs. Our experiment suggests that headache caused by direct
      nitric oxide (NO) action in the continued presence of NO is very resistance to
      analgesics and to specific acute migraine treatments. This suggests that NO works
      very deep in the cascade of events associated with vascular headache, whereas
      tested drugs work higher in the cascade. The model suggested here should
      therefore be tested with other headache/migraine-provoking agents that supposedly
      work higher in the cascade of events. The need for human models persists, but the
      solution to this problem is still pending.

PMID- 19740121
TI  - Whiplash headache: does the diagnosis make more harm than the whiplash?

PMID- 19740122
TI  - Hyperinsulinaemia in migraineurs is associated with nitric oxide stress.
AB  - There is growing evidence that alterations in the insulin and glucose metabolism
      may be involved in the pathogenesis of migraine. Nitric oxide (NO) stress has
      been associated with migraine. However, the role of NO on the insulin and glucose
      metabolism in migraineurs has remained elusive to date. The aim of the present
      study was to investigate the insulin and glucose metabolism in migraineurs and to
      determine possible interactions with the NO pathway. One hundred and twenty non
      obese probands participated in this study, including 48 migraineurs and 72
      healthy volunteers. Various parameters of the NO pathway, glucose metabolism as
      well as body measurement parameters were determined. We found a highly
      significantly increased insulin and Homeostasis Model Assessment (HOMA)-index in
      migraine patients, whereas fasting glucose was decreased. Logistic regression
      revealed an odds ratio of 5.67 for migraine, when comparing the lowest with the
      highest quartile of HOMA. Multivariate analysis showed that HOMA, waist-to-length
      ratio and nitrite as parameters of NO stress were highly significantly
      correlated. We show here that hyperinsulinaemia is associated with migraine and,
      furthermore, is correlated with increased NO stress. These findings represent a
      new pathophysiological mechanism that may be of clinical relevance.

PMID- 19740123
TI  - Post-craniotomy headache: a proposed revision of IHS diagnostic criteria.
AB  - Seventy-nine patients with intracranial aneurysms were evaluated in the
      presurgical period, and followed up to 6 months after surgery. We compare
      patients who fulfilled with those that did not post-craniotomy headache (PCH)
      diagnostic criteria, according to the International Classification of Headache
      Disorders. Semistructured interviews, headache diaries, Short Form-36 and McGill
      Pain Questionnaire were used. Seventy-two patients (91%) had headaches during the
      follow-up period. The incidence of PCH according to the International Headache
      Society diagnostic criteria was 40%. Age, sex, type of surgery, temporomandibular
      disorder, vasospasm, presence and type of previous headaches, and subarachnoid
      haemorrhage were not related to headache classification. There were no
      differences in the quality of life, headache frequency and characteristics or
      pain intensity between patients with headache that fulfilled or not PCH criteria.
      We proposed a revision of the diagnostic criteria for PCH, extending the headache
      outset after surgery from 7 to 30 days, and including the presence of headaches
      after surgery in patients with no past history of headaches, or an increase in
      headache frequency during the first 30 days of the postsurgical period followed
      by a decrease over time. Using these criteria we would classify 65% of our
      patients as having PCH.

PMID- 19740124
TI  - Are there differences between cephalic and extracephalic cutaneous allodynia in
      migraine patients?
AB  - Cutaneous allodynia (CA), pain in response to innocuous cutaneous stimuli, is
      recognized as a sign of central sensitization during migraine episodes. It is
      either restricted within the pain area on the ipsilateral head, or extends within
      and outside the head. Moreover, CA can be elicited in response to thermal (heat
      or cold) and/or mechanical stimuli. This raises the question as to whether
      cephalic and extracephalic CAs share the same properties. We assessed cephalic
      and extracephalic CAs in migraine episodic patients using a questionnaire
      completed at home during migraine attacks. A total of 67 episodic migraine
      patients (58 women, nine men; 4013 years old) addressed all questions in the
      questionnaire. Forty-nine patients (73%) cited one or more allodynic symptoms
      during or immediately after the migraine attack. Almost all 49 patients reported
      cephalic CA, whereas 24 (49%) also reported extracephalic CA. Occurrence and
      extension of CA correlated (P = 0.005) with headache intensity. Modalities of
      cephalic and extracephalic CA were different (chi2 = 12.03; P = 0.002),
      extracephalic CA being mostly thermal (75%) whereas cephalic CA was mostly
      mechanical (92%). This suggests that cephalic and extracephalic CAs involve
      different mechanisms.

PMID- 19740125
TI  - Response to Seshia S et al.: The classification of chronic headache: room for
      further improvement? Chronic headache classification.

PMID- 19740126
TI  - Desloratadine relieves nasal congestion and improves quality-of-life in
      persistent allergic rhinitis.
AB  - BACKGROUND: Symptoms of allergic rhinitis (AR), particularly nasal congestion,
      can impair quality-of-life (QoL). However, only a modest correlation exists
      between these symptoms and Rhinoconjunctivitis Quality of Life Questionnaire
      (RQLQ) scores, suggesting that both be evaluated for a complete assessment of
      health. METHODS: Subjects with a > or =2-year history of moderate-to-severe AR to
      dust mite or cat dander were randomized to desloratadine 5 mg/day (n = 293) or
      placebo/day (n = 291) for 28 days. Primary endpoint was change from baseline in
      a.m./p.m. nasal congestion score. Secondary outcomes included change from
      baseline in total nasal symptom score, individual symptom scores and RQLQ scores
      (completed on days 1, 7, and 28). RESULTS: The Allergic Rhinitis and its Impact
      on Asthma criteria for persistent allergic rhinitis (PER) were fulfilled by 99%
      of subjects in the placebo arm. Between-treatment difference in a.m./p.m. nasal
      congestion score, observed from day 8 onward, significantly favored desloratadine
      (P = 0.0003). Desloratadine significantly improved a.m./p.m. nasal congestion and
      RQLQ scores after 1 week and at treatment end (P < 0.05). Improvements in 5 of 7
      RQLQ domain scores exceeded the minimal important difference. On days 7 and 28,
      desloratadine was also significantly superior to placebo in mean change from
      baseline in a.m./p.m. total nasal symptom score and rhinorrhea score (both P < or
      = 0.01). Symptomatic benefit was primarily driven by improvement in nasal
      congestion and rhinorrhea. CONCLUSIONS: Desloratadine 5 mg/day significantly
      improved symptoms associated with PER, including nasal congestion, and provided
      significant improvement in QoL after 1 week of treatment.

PMID- 19740127
TI  - Treatment-resistant bipolar depression: towards a new definition.
AB  - OBJECTIVE: To summarize the conceptual and operational definitions of treatment
      resistant bipolar depression and to review the evidence-based therapeutic
      options. METHOD: Structured searches of PubMed, Index Medicus, Excerpta Medica
      and Psyclit conducted in December 2008. RESULTS: Criteria for treatment
      resistance in bipolar depression are commonly based on concepts stemming from
      treatment resistance as defined for unipolar depression, an approach that proved
      to be inadequate. In fact, the addition of an ad hoc criterion based on lithium
      and other mood stabilizer unresponsiveness after reaching adequate plasma levels
      appears to be a patch that attempts to take into account the uniqueness of
      bipolar depression but fails to become operational. Recent data from randomized
      clinical trials of new anticonvulsants and second-generation antipsychotics
      should lead to the development of a modern definition of treatment-resistant
      bipolar depression, and specific therapeutic algorithms. CONCLUSION: We suggest a
      redefinition of resistant bipolar I and II depression. We propose different
      degrees of severity within bipolar depression in a stepwise manner.

PMID- 19740128
TI  - Early loss of pregnancy after intravitreal bevacizumab injection.

PMID- 19740129
TI  - Limited long-term efficacy of intravitreous anti-VEGF pharmacotherapy in
      sarcoidosis complicated by peripapillary choroidal neovascular membrane.

PMID- 19740130
TI  - The need and total cost of Finnish eyecare services: a simulation model for 2005
      2040.
AB  - PURPOSE: The aims of this study were: (i) to create a structural simulation model
      capable of predicting the future need and cost of eyecare services in Finland;
      and (ii) to test and rank different policy alternatives for access to care and
      the required physician workforce. METHODS: Using the system dynamics approach,
      the number and cost of patients with cataract, glaucoma, diabetic retinopathy and
      age-related macular degeneration (AMD) were described with causal-loop diagrams
      and were then translated into a set of mathematical equations to build a computer
      simulation model. Mathematically, the problem was formulated as a set of
      differential equations that were solved numerically with specialized software.
      The validity of the model was tested against prevalence and administrative
      historical data. The costs covered by the public sector in Finland were obtained
      from 2003 from the Finnish Hospital Discharge Register (including outpatient
      care), the Finnish Social Insurance Institution and a survey of hospital price
      lists. Different levels of access to public care were then simulated in four eye
      diseases, for which the model estimated the need for services and resources and
      their costs in the years 2005-2040. RESULTS: The model forecasted that the
      adoption of the 2005 national 'access to care' criteria for cataract surgery
      would shorten waiting lists. If the workload of Finnish ophthalmologists were
      kept at the 2003 level, the graduation rate of new ophthalmologists would have to
      increase by 75% from the current level. If all glaucoma patients were followed in
      the public sector in future, even this increase in training would not meet the
      demand for physician workforce. The current model indicated that the screening
      frequency of diabetes can be increased without large sacrifices in terms of
      costs. AMD therapy has a significant role in the allocation of future resources
      in eyecare. The modelling study predicted that ageing alone will increase the
      costs of eyecare during the next four decades in Finland by about 1% per year in
      real terms (undiscounted and without inflation of unit costs). The increases in
      total yearly costs were on average 8.6% between 2001 and 2003. CONCLUSIONS: The
      results of this modelling study indicate that policy initiatives, such as
      defining criteria for access to care, can have substantial implications on the
      demand for care and waiting times whereas the effect of ageing alone was
      relatively small. Measures to control several other factors - such as the
      adoption and price level of new technologies, treatments and practice patterns -
      will be at least equally important in order to restrain healthcare costs
      effectively.

PMID- 19740131
TI  - Operant behavior and alcohol levels in blood and brain of alcohol-dependent rats.
AB  - BACKGROUND: The purpose of the present investigation was to more clearly define
      blood-alcohol parameters associated with alcohol dependence produced by alcohol
      vapor inhalation and alcohol-containing liquid diet. METHODS: Alcohol levels in
      blood and brain were compared during and after 4 hours of acute alcohol vapor
      exposure; also, brain-alcohol levels were assessed in alcohol-exposed (14-day
      alcohol vapor) and alcohol-naive rats during and after 4 hours of acute alcohol
      vapor exposure. A separate group of rats were implanted with i.v. catheters, made
      dependent on alcohol via vapor inhalation, and tested for operant alcohol
      responding; blood-alcohol levels (BALs) were measured throughout operant alcohol
      drinking sessions during alcohol withdrawal. A final group of rats consumed an
      alcohol-liquid diet until they were dependent, and those rats were then tested
      for operant behavior at various withdrawal time points; BALs were measured at
      different withdrawal time points and after operant sessions. RESULTS: Blood- and
      brain-alcohol levels responded similarly to vapor, but brain-alcohol levels
      peaked at a higher point and more slowly returned to zero in alcohol-naive rats
      relative to alcohol-exposed rats. Alcohol vapor exposure also produced an upward
      shift in subsequent operant alcohol responding and resultant BALs. Rats consumed
      large quantities of alcohol-liquid diet, most of it during the dark cycle,
      sufficient to produce high blood-alcohol levels and elevated operant alcohol
      responding when tested during withdrawal from liquid diet. CONCLUSIONS: These
      results emphasize that the key determinants of excessive alcohol drinking
      behavior are the BAL range and pattern of chronic high-dose alcohol exposure.

PMID- 19740132
TI  - Alcohol and cognitive function: assessment in everyday life and laboratory
      settings using mobile phones.
AB  - BACKGROUND: Mobile phone (cellphone) technology makes it practicable to assess
      cognitive function in a natural setting. We assessed this method and compared
      impairment of performance due to alcohol in everyday life with measurements made
      in the laboratory. METHODS: Thirty-eight volunteers (20 male, aged 18-54 years)
      took part in the everyday study, completing assessments twice a day for 14 days
      following requests sent by text messages to the mobile phone. Twenty-six of them
      (12 male, aged 19-54) took part in a subsequent two-period crossover lab study
      comparing alcohol with no alcohol (placebo). RESULTS: Everyday entries with 5 or
      more units of alcohol consumed in the past 6 hours (inferred mean blood alcohol
      concentration 95 ml/100 ml) showed higher scores for errors in tests of attention
      and working memory compared with entries with no alcohol consumed that day.
      Response times were impaired for only 1 test, sustained attention to response.
      The laboratory comparison of alcohol (mean blood alcohol concentration 124 mg/100
      ml) with placebo showed impairment to both reaction time and error scores for all
      tests. A similar degree of subjective drunkenness was reported in both settings.
      CONCLUSIONS: We found that mobile phones allowed practical research on cognitive
      performance in an everyday life setting. Alcohol impaired function in both
      laboratory and everyday life settings at relevant doses of alcohol.

PMID- 19740133
TI  - The mammalian circadian clock exhibits acute tolerance to ethanol.
AB  - BACKGROUND: Tolerance to ethanol is observed over a variety of time courses, from
      minutes to days. Acute tolerance, which develops over 5 to 60 minutes, has been
      observed for both behavioral and neurophysiological variables and may involve
      changes in signaling through NMDA, GABA, or other receptors. Previous work has
      shown that both acute and chronic ethanol treatments modulate photic and
      nonphotic phase resetting of the mammalian circadian clock located in the
      suprachiasmatic nucleus (SCN). Although not specifically tested, the data thus
      far do not point to the development of chronic tolerance to the modulatory
      effects of ethanol. Here we investigated whether acute tolerance the ethanol
      occurs with respect to in vitro phase modulation of the SCN clock. METHODS: Mouse
      brain slices containing the SCN were pretreated with ethanol for varying lengths
      of time, followed by treatment concurrent with either glutamate or the serotonin
      agonist, 8-hydroxy-DPAT (DPAT). The phase of the SCN circadian clock was assessed
      the following day through extracellular recordings of SCN neuronal activity. SCN
      neuronal activity normally peaks during mid-day, and this rhythm can be shifted
      by treatment with either glutamate or DPAT. RESULTS: While concurrent treatment
      of SCN-containing brain slices with ethanol and glutamate blocks glutamate
      induced phase delays of the SCN clock, pretreating the slices with ethanol for >
      or =15 minutes prevents this inhibition. Likewise, while concurrent treatment
      with ethanol and DPAT enhances DPAT-induced phase advances of the SCN clock,
      pretreating the slices with ethanol for > or =30 minutes prevents this
      enhancement. CONCLUSIONS: Both the inhibiting and enhancing effects of ethanol on
      in vitro SCN clock phase resetting show acute tolerance. Additional experiments
      are needed to determine whether more slowly developing forms of tolerance also
      occur with respect to the SCN circadian clock.

PMID- 19740134
TI  - Selected line difference in the effects of ethanol dependence and withdrawal on
      allopregnanolone levels and 5alpha-reductase enzyme activity and expression.
AB  - BACKGROUND: Allopregnanolone (ALLO) is a progesterone derivative that rapidly
      potentiates gamma-aminobutyric acid(A) (GABA(A)) receptor-mediated inhibition and
      modulates symptoms of ethanol withdrawal. Because clinical and preclinical data
      indicate that ALLO levels are inversely related to symptoms of withdrawal, the
      present studies determined whether ethanol dependence and withdrawal
      differentially altered plasma and cortical ALLO levels in mice selectively bred
      for differences in ethanol withdrawal severity and determined whether the
      alterations in ALLO levels corresponded to a concomitant change in activity and
      expression of the biosynthetic enzyme 5alpha-reductase. METHODS: Male Withdrawal
      Seizure-Prone (WSP) and -Resistant (WSR) mice were exposed to 72 hours ethanol
      vapor or air and euthanized at select times following removal from the inhalation
      chambers. Blood was collected for analysis of ALLO and corticosterone levels by
      radioimmunoassay. Dissected amygdala, hippocampus, midbrain, and cortex as well
      as adrenals were examined for 5alpha-reductase enzyme activity and expression
      levels. RESULTS: Plasma ALLO was decreased significantly only in WSP mice, and
      this corresponded to a decrease in adrenal 5alpha-reductase expression. Cortical
      ALLO was decreased up to 54% in WSP mice and up to 46% in WSR mice, with a
      similar decrease in cortical 5alpha-reductase activity during withdrawal in the
      lines. While cortical gene expression was significantly decreased during
      withdrawal in WSP mice, there was a 4-fold increase in expression in the WSR line
      during withdrawal. Hippocampal 5alpha-reductase activity and gene expression was
      decreased only in dependent WSP mice. CONCLUSIONS: These results suggest that
      there are line and brain regional differences in the regulation of the
      neurosteroid biosynthetic enzyme 5alpha-reductase during ethanol dependence and
      withdrawal. In conjunction with the finding that WSP mice exhibit reduced
      sensitivity to ALLO during withdrawal, the present results are consistent with
      the hypothesis that genetic differences in ethanol withdrawal severity are due,
      in part, to modulatory effects of GABAergic neurosteroids such as ALLO.

PMID- 19740135
TI  - BOLD response during spatial working memory in youth with heavy prenatal alcohol
      exposure.
AB  - BACKGROUND: Prenatal alcohol exposure has been consistently linked to
      neurocognitive deficits and structural brain abnormalities in affected
      individuals. Structural brain abnormalities observed in regions supporting
      spatial working memory (SWM) may contribute to observed deficits in visuospatial
      functioning in youth with fetal alcohol spectrum disorders (FASDs). METHODS: We
      used functional magnetic resonance imaging (fMRI) to assess the blood oxygen
      level dependent (BOLD) response in alcohol-exposed individuals during a SWM task.
      There were 22 young subjects (aged 10-18 years) with documented histories of
      heavy prenatal alcohol exposure (ALC, n = 10), and age- and sex-matched controls
      (CON, n = 12). Subjects performed a SWM task during fMRI that alternated between
      2-back location matching (SWM) and simple attention (vigilance) conditions.
      RESULTS: Groups did not differ on task accuracy or reaction time to the SWM
      condition, although CON subjects had faster reaction times during the vigilance
      condition (617 millisecond vs. 684 millisecond, p = 0.03). Both groups showed
      similar overall patterns of activation to the SWM condition in expected regions
      encompassing bilateral dorsolateral prefrontal lobes and parietal areas. However,
      ALC subjects showed greater BOLD response to the demands of the SWM relative to
      the vigilance condition in frontal, insular, superior, and middle temporal,
      occipital, and subcortical regions. CON youth evidenced less increased brain
      activation to the SWM relative to the vigilance task in these areas (p < 0.05,
      clusters > 1,664 microl). These differences remained significant after including
      Full Scale IQ as a covariate. Similar qualitative results were obtained after
      subjects taking stimulant medication were excluded from the analysis.
      CONCLUSIONS: In the context of equivalent performance to a SWM task, the current
      results suggest that widespread increases in BOLD response in youth with FASDs
      could either indicate decreased efficiency of relevant brain networks, or serve
      as a compensatory mechanism for deficiency at neural and/or cognitive levels. In
      context of existing fMRI evidence of heightened prefrontal activation in response
      to verbal working memory and inhibition demands, the present findings may
      indicate that frontal structures are taxed to a greater degree during cognitive
      demands in individuals with FASDs.

PMID- 19740136
TI  - Detecting alcohol-related problems in developing countries: a comparison of 2
      screening measures in India.
AB  - BACKGROUND: There is inadequate recognition of alcohol misuse as a public health
      issue in India. Information on screening measures is critical for prevention and
      early intervention efforts. This study critically evaluated the full and shorter
      versions of the AUDIT and RAPS4-QF as screening measures for alcohol use
      disorders (AUDs) in a community sample of male drinkers in Goa, India. METHODS:
      Data from male drinking respondents in a population study on alcohol use patterns
      and sexual risk behaviors in randomly selected rural and urban areas of North Goa
      are reported. Overall, 39% (n = 743) of the 1899 screened men, age 18 to 49,
      reported consuming alcohol in the last 12 months. These current drinkers were
      administered the screening measures as part of detailed interviews on drinking
      patterns and AUD symptoms. Receiver Operating Characteristic (ROC) analysis was
      conducted for each combination of screening measure and criterion (alcohol
      dependence or any AUD). Reliability and correlations among the 4 measures were
      also examined. RESULTS: All 4 measures performed well with area under the curves
      of at least 0.79. The full screeners that included both drinking patterns and
      problem items (the AUDIT and the RAP4-QF) performed better than their shorter
      versions (the AUDIT-C and the RAPS4) in detecting AUDs. Performance of the AUDIT
      and RAPS4-QF improved with lowered and raised thresholds, respectively, and
      alternate cut-off scores are suggested. Scores on the full measures were
      significantly correlated (0.80). Reliability estimates for the AUDIT measures
      were higher than those for the RAPS4 measures. CONCLUSIONS: All measures were
      efficient at detecting AUDs. When screening for alcohol-related problems among
      males in the general population in India, cut-off scores for screeners may need
      to be adjusted. Selecting an appropriate screening measure and cut-off score
      necessitates careful consideration of the screening context and resources
      available to confirm alcohol-related diagnoses.

PMID- 19740137
TI  - Prevalence and patterns of alcohol consumption and health-risk behaviors among
      high school students in Thailand.
AB  - BACKGROUND: Underage drinking is a significant social and public health problem
      in Thailand. We report the prevalence and patterns of alcohol consumption and
      associated health-risk behaviors using data from a 2007-2008 national school
      survey. METHOD: A cross-sectional survey using a self-administered questionnaire
      was conducted among 50,033 high school and vocational college students from 201
      schools in 40 provinces between December 2007 and February 2008. RESULTS: The
      prevalence rates of past-year drinking, past-30-day binge drinking, and drinking
      until intoxication were 25.5, 9.5, and 17.3% in boys and 14.5, 3.7, and 7.2% in
      girls, respectively. Higher school levels, lower grades, living with someone
      other than their own parents, and having family members with substance or alcohol
      problems were significantly associated with all kinds of drinking. Binge drinkers
      were significantly more likely to have drinking consequences, e.g., driving after
      drinking, nausea and vomiting, and having a hangover than were nonbinge drinkers.
      The rates of other behavior and emotional problems were 2.5 to 6.7 times as
      likely in drinkers as nondrinkers, including smoking (35.1% vs. 4.9%),
      prescription drug misuse (17.7% vs. 6.7%), illicit substance use (17.8% vs.
      2.4%), carrying a weapon (6.5% vs. 1.8%), feeling depressed (23.2% vs. 10.9%),
      suicidal attempt (10.5% vs. 3.8%), and sexual intercourse (30.5% vs. 5.7%).
      CONCLUSION: Alcohol consumption is a serious problem among adolescents in
      Thailand and is strongly associated with various health-risk behaviors. Effective
      age- and gender-specific interventions should be implemented to discourage
      underage drinking and associated adverse health and social consequences.

PMID- 19740138
TI  - Physical health and severe mental illness: if we don't do something about it, who
      will?

PMID- 19740139
TI  - An examination of frequent nursing interventions and outcomes in an adolescent
      psychiatric inpatient unit.
AB  - Little is known about which nursing interventions used in adolescent psychiatric
      inpatient treatment demonstrate improvements in outcome in the 'real world'
      setting, despite an increase in external outcomes reporting requirements.This
      paper examines nursing and other multidisciplinary interventions commonly used at
      the Youth Inpatient Unit, Christchurch, New Zealand, in relation to improvements
      in outcomes as measured by the Health of the Nation Outcome Scales for Children
      and Adolescents, utilizing data gathered prospectively as part of an ongoing
      quality assurance and outcomes project. We found the majority of interventions
      investigated were utilized equally across diagnostic groups, although stress
      management and problem-solving education was used more for patients with mixed
      affective disorders. Further, the results contribute to growing evidence toward
      the value of providing medication and problem-solving education to this
      population. Mental health nurses working with children and adolescents should be
      supported to utilize and develop their unique skill set to offer targeted
      interventions and to examine their practice to identify the most valuable
      interventions for their patients within this developmental context.

PMID- 19740140
TI  - A qualitative exploration of communication within the community mental health
      team.
AB  - This qualitative study sought to explore conceptual models employed by community
      mental health team (CMHT) staff in the care of their clients and how CMHT
      clinicians communicated with one another, particularly in relation to complex
      clinical work. The qualitative method of interpretive phenomenological analysis
      was used, and semistructured in-depth interviews with seven UK CMHT clinicians
      were conducted and analyzed. Four themes were evident in the data and showed that
      clinicians face complex and competing demands and draw on a range of therapeutic
      models in their work. It was also clear that much discussion centred primarily on
      pragmatic issues and lacked conceptual depth. The results underline the complex
      and challenging nature of CMHT work and suggest that a more systematic approach
      to interdisciplinary training within teams could be beneficial in increasing
      clinicians' knowledge, skills, and their understanding of the conceptual models
      used across different disciplines.

PMID- 19740141
TI  - Self-esteem in patients treated for anorexia nervosa.
AB  - Anorexia nervosa (AN) mainly affects girls or women between 13 and 45 years of
      age. According to previous studies, one of the reasons for the desire to be thin
      is low self-esteem. The purpose of the study was to examine the self-esteem of 38
      female patients with AN between 16 and 25 years of age, before and after 3 months
      of treatment at a specialist ward for eating disorders in Goteborg, Sweden. A
      quantitative pre- and post-assessment based on two self-rating questionnaires,
      the Rosenberg Self-Esteem Scale (RSE-S) and three subscales (weight phobia, body
      dissatisfaction, and ineffectiveness) of Eating Disorder Inventory-2 (EDI-2),
      together with body mass index (BMI), were used in the study, which was conducted
      between June 2005 and March 2008. The results reveal that self-esteem, BMI,
      weight phobia, and body dissatisfaction improved significantly between pre- and
      post-treatment. The RSE-S and EDI-2 ineffectiveness correlate highly with one
      another, which lends support to convergent validity, and the internal consistency
      was high for both the RSE-S and EDI-2 ineffectiveness. The results indicate that
      the treatment was effective, as both patients' self-esteem and BMI increased
      after completed treatment, which was the primary goal of the treatment at this
      ward. Future studies should focus on follow up and the way self-esteem manifests
      itself at different points in time within an individual.

PMID- 19740142
TI  - Patients' experiences of absconding from a psychiatric setting in Indonesia.
AB  - Absconding from psychiatric institutions is a relatively common phenomenon. Yet
      patients' experience of absconding is a perspective that has received little
      attention in the West and none in Indonesia. A case study using mixed methods was
      undertaken in order to provide a profile of absconding events over a 1-year
      period in a psychiatric setting in Indonesia. In the qualitative phase of the
      study, in a semistructured interview, 16 patients who absconded described their
      experiences of absconding. Three themes of experience were identified: the call
      to home, hopes and realities, and us and them. The call to home theme described
      patients' eagerness to connect with family and others and to feel safe. Hopes and
      realities identified patients' hopes for happiness, which were dashed by the
      realities of life at home and in the hospital. The final theme, us and them,
      described the competing interests and different opinions of patients in relation
      to others including hospital staff and family. There is a need for changes to
      mental health policy and service provision in order to reduce the incidence of
      absconding in Indonesia and enable patients and their families to receive
      adequate support while living in the community.

PMID- 19740143
TI  - Personality traits among burnt out and non-burnt out health-care personnel at the
      same workplaces: a pilot study.
AB  - Stress-related illnesses, such as burnout, have increased over the last decade,
      but not everyone at the same workplace develops burnout, suggesting that
      individual factors may contribute to this phenomenon. The aim of this study was
      to describe patterns of personality traits among two groups of health-care
      personnel from the same workplaces, one group on sick leave due to medically
      assessed burnout, and one group with no indication of burnout, respectively.
      Fourteen psychiatric- (n = 7) and elderly (n = 7)-care units, located in one
      specific area in a municipality in northern Sweden, participated in this
      questionnaire-based study. The participants (n = 40), on sick leave due to
      medically-assessed burnout (n = 20), and those with no indication of burnout (n =
      20), respectively, completed Cattell's 16 Personality Factors Questionnaire
      between February and December 2004. Conventional statistical methods and partial
      least square regression were used to analyze data. The results showed that the
      burnout group had lower scores regarding emotional stability and higher scores
      regarding anxiety than the non-burnout group, but the results also showed a wide
      variation of personality traits within groups. The most important indicators for
      belonging to the burnout group were 'openness to changes' and 'anxiety', and for
      belonging to the non-burnout group, 'emotional stability', 'liveliness',
      'privateness' (i.e. forthright or discreet), and 'tension'. The result indicates
      complex interactions between personality traits and the context in which the
      individual lives. It seems to be important to increase our awareness of when
      personality traits may constitute opportunities versus risks in dealing with
      one's existing circumstances.

PMID- 19740144
TI  - Preparing mental health nurses for the future workforce: an exploration of
      postgraduate education in Victoria, Australia.
AB  - Problems with recruitment and retention in the mental health nursing workforce
      have been consistently acknowledged in the Australian literature. An Australian
      workforce scoping study conducted in 1999 revealed a significant shortfall
      between the number of nurses completing postgraduate mental health nursing
      programmes and both current and future workforce demands. Despite this, there has
      been no systematic analysis of these programmes to explain why they are not
      meeting workforce expectations. The primary aim of the current study was to
      elicit information about the number of applicants, enrolments, and completions
      during the 5-year period, 2000-2004. This information was obtained through
      structured interviews with representatives from Victorian universities (n = 6)
      who offered postgraduate mental health nursing programmes. Supplementary
      information, such as approaches to course advertising and student demographics,
      was also collected. The findings showed an overall increase in the number of
      students applying to and completing these degrees, although changes in the level
      of programmes students undertook were evident during this period. Despite
      revealing important insights regarding postgraduate mental health nursing courses
      within Victorian universities, the lack of systematic and comprehensive data
      collection was identified as a problem that limits the extent to which university
      data can inform recruitment strategies.

PMID- 19740145
TI  - Caregiver experience in mental illness: a perspective from a rural community in
      South Africa.
AB  - After the democratization of South Africa in 1994, the health-care system was
      reorganized in accordance with the primary health-care philosophy advocated by
      the World Health Organization. This was accompanied by a process of
      deinstitutionalization of mental health-care services, which has led families to
      become the main providers of care to individuals with mental illness. This study
      explores the experiences of informal family caregivers of persons with mental
      illness in a rural area in South Africa. Data were collected through eight
      individual semistructured interviews of informal caregivers who cared for
      relatives with mental illness and collect medications monthly at a community
      clinic in the Makhuduthamaga local municipality in Limpopo, South Africa. A
      qualitative research design was used, which was explorative, descriptive, and
      contextual. The data analysis revealed four major themes: (i) experiences of
      providing for physiological/physical needs; (ii) experiences of providing for
      emotional needs; (iii) experiences of providing for security needs; and (iv)
      experiences associated with the medical health-care programme. The study revealed
      that the experiences of family caregivers were conceptualized negatively,
      although the interview questions were intentionally neutral. This is believed to
      be due to the cultural explanatory models of mental illness prevalent in this
      region of South Africa. It is suggested that to increase compliance with
      medication, reduce relapse, and mitigate stigma associated mental illness,
      medical professionals need to incorporate aspects of cultural explanatory models
      into their explanations of the causes of illness.

PMID- 19740146
TI  - Redressing the balance in mental health nursing education: arguments for a values
      based approach.
AB  - Evidence-based practice (EBP) has become a dominant epistemology in nursing
      education, and has devalued the complex interpersonal components of mental health
      nursing. A curriculum for mental health nursing, which values the personhood of
      service users, should focus on those processes that promote recovery within a
      therapeutic relationship committed to collaboration and respect for diversity.
      These relationships become possible where the preparation of mental health nurses
      for practice includes an examination of self in terms of beliefs and values and
      their consequences on others. The combination of action and reflection in praxis
      provides a means by which self-examination and professional obligation can be
      examined in order to construct a moral identity, which is responsive to the needs
      of people with mental health problems. Praxis is more than a means of reflecting
      on practice: it draws together skill, practice knowledge, attitudinal style, and
      moral reasoning. For this reason, ethical values have a vital role to play in the
      development of contemporary nursing praxis.

PMID- 19740148
TI  - Beers' criteria--is it relevant to dentistry?

PMID- 19740149
TI  - Oral health outcomes in an adult dental population: the impact of payment
      systems.
AB  - This study compared the effect of payment systems on recall visits and oral
      health outcomes for four patient payer groups. The authors reviewed recall audit
      data obtained over a 4-year period. Dental payer groups in the study population
      differed with respect to dental outcomes. Patients who had recall visits at 1
      year or longer had worse outcomes than patients seen more frequently. A Medicaid
      subgroup with the greatest number of risk factors displayed improved oral health
      outcomes when seen on a more frequent recall schedule. Study findings suggest
      that, given the increased risks to maintaining oral health, patients being
      supported by public-funded programs would benefit from more frequent recalls.
      Such an emphasis would appear to provide the opportunity to improve outcomes in
      disadvantaged populations and increase the quality of care offered.

PMID- 19740150
TI  - Caries experience in individuals with cerebral palsy in relation to oromotor
      dysfunction and dietary consistency.
AB  - The aim of this study was to investigate caries experience in individuals with
      cerebral palsy (CP) who have oromotor dysfunction and relate it to age and
      dietary consistency. Noninstitutionalized individuals with CP (n = 108) aged 4-19
      years (mean: 10 years, 1 month +/- SD 4 years, 5 months) were recruited for this
      study. Subjects who were severely impaired (35.2%) had orofacial motor
      dysfunction most frequently, followed by those who were slightly affected
      (27.7%), moderately affected (20.4%), and very slightly affected (16.7%). Age was
      a statistically significant factor for oromotor dysfunction (p= 0.007), with the
      youngest individuals having the most severe oromotor problems. Dietary
      consistency and oromotor function were statistically significant influence on the
      DMF index (p= 0.0352). The highest total DMF values were measured for individuals
      who were severely impaired and also the youngest, as well as for those receiving
      liquid diets. Early rehabilitation, intervention, and prevention are important
      for these individuals.

PMID- 19740151
TI  - Oral home telecare for adults with tetraplegia: a feasibility study.
AB  - This pilot study investigated the feasibility of delivering an individualized
      program of oral home telecare training using PC-based, real-time interactive
      videoconferencing via the Internet to meet the unique challenges of dental care
      for people with tetraplegia. A home-based videoconferencing method was tested
      with two adults with tetraplegia and an occupational therapist (rehabilitation
      specialist). As part of the proposed rehabilitation training to improve
      independence in performing oral hygiene, adaptive devices (a rechargeable
      oscillating-rotating power toothbrush and a cordless oral irrigator) were
      introduced to facilitate oral care performance with interactive, Web-based
      instruction. Training was conducted once a week for 4 weeks. The oral home
      telecare experience was evaluated using a questionnaire and in-depth interviews
      after the training. Both subjects were satisfied with the oral home telecare
      services and were enthusiastic about using the services without major difficulty
      after having previously experienced barriers to dental care. In addition to their
      positive perceptions about videoconferencing, the subjects suggested adaptations
      and identified unexpected potential uses for interactive videoconferencing. The
      use of interactive videoconferencing as a mode of oral hygiene training may lead
      to a change in oral hygiene service delivery methods, improving accessibility to
      geographically dispersed populations with tetraplegia. Oral home telecare offers
      strategies to decrease physical barriers and communication difficulties that
      correspond to recommendations to improve the quality of dental health services
      for people with tetraplegia.

PMID- 19740152
TI  - Masticatory dysfunction in patients with myotonic dystrophy (type 1): a 5-year
      follow-up.
AB  - Eight patients with myotonic dystrophy type 1, DM1 (age range 45-63 years) were
      followed for a period of 5 years. Two sets of data analyzing masticatory function
      and activities of daily living (ADL) were obtained at baseline and at 5 years.
      The results from both time points were compared. The number of food items
      considered easy to chew, maximum bite force, occlusal contact area, number of
      teeth, and ADLs were significantly reduced (p < 0.05) at the second assessment
      when compared to the first. During the intervening 5 years, six of the eight
      patients adopted a soft diet. These results suggest deterioration in ADLs and
      masticatory function of patients with DM1. Continuous evaluation of the feeding
      ability and the type of diet are necessary for patients with DM1.

PMID- 19740153
TI  - Fluoxetine-induced sleep bruxism in an adolescent treated with buspirone: a case
      report.
AB  - Sleep bruxism, the involuntary grinding and/or clenching of teeth during sleep,
      may occur in young children and may be secondary to medication use, especially
      selective serotonin reuptake inhibitors (SSRIs). The mesocortical disinhibition
      produced by SSRIs may lead to dopamine depletion that manifests itself as
      nocturnal bruxism, a specific form of akathisia. This may be prevented by using
      buspirone, a 5-HT1A agonist that reduces serotonergic activity and increases
      dopaminergic activity. This article reports on a case history of an adolescent
      with fluoxetine-induced bruxism that was successfully treated with buspirone. As
      SSRI use is on the rise for treating childhood psychiatric disorders, this case
      report highlights the importance of recognizing SSRI-induced bruxism and the
      possible related adverse dental side effects. Furthermore, this report supports
      the efficacy of a treatment strategy in adolescents, which has previously been
      reported only for adult patients.

PMID- 19740154
TI  - Improving oral healthcare: improving the quality of life for patients after a
      stroke.
AB  - With the increase in the elderly population, the prevalence of systemic diseases
      such as strokes and heart attacks will also increase. Persons who have had a
      stroke will be more susceptible to mistreatment, neglect, abuse, and aspiration
      pneumonia. The expansion of the elderly population will make the training of
      professional healthcare workers and other auxiliaries extremely important.
      Quality of life can be maintained if poor oral health is reduced through better
      daily oral hygiene practices. Informing others about the known association
      between oral health and systemic diseases will increase the awareness of the need
      for good oral hygiene in order to reduce the risk of systemic diseases.
      Healthcare professionals must also be able to recognize, document, and report to
      Adult Protective Services suspected abuse such as physical and dental neglect.
      The networking of healthcare providers with Adult Protective Services and other
      professional disciplines will provide a collaborative approach to assure
      successful integration of healthcare protocols for the elderly population.

PMID- 19740156
TI  - Commentary: STARR and Transtar procedures.

PMID- 19740157
TI  - Histopathology reporting in colorectal cancer: a proforma improves quality.
AB  - AIM: The histopathology report is vital to determine the need for adjuvant
      therapy and prognosis in colorectal cancer (CRC). Completeness of those in text
      format is inadequate. This study evaluated the improvement of quality of
      histopathology reports following the introduction of a template proforma, based
      on standards set by the Royal College of Pathologists (RCP), UK. METHOD: Sixty
      eight consecutive histopathology reports based on 19 items for rectal cancer (RC)
      and 15 items for colon cancer (CC) using the proforma were prospectively analysed
      and compared with results of a previous audit of 82 consecutive histopathology
      reports in text format. The percentage of reports containing a statement for each
      data item for both series was compared using the Normal test for difference
      between two proportions. Completeness of each report was assessed and a
      percentage score (percentage completeness) was given. Mean percentage
      completeness was calculated for each format and compared using the two sample t
      test. RESULTS: Except for comments on the presence of 'histologically confirmed
      liver metastases' in CC and RC, 'distance from dentate line' and 'distance to
      circumferential margin' in RC, all other items were commented in more than 90% of
      reports, where 71% of the items based on the minimum data set were present in all
      reports. Compared to prose format, the mean percentage completeness (SD) improved
      from 74% (8) to 91% (4) (P < 0.0001) and from 81% (5) to 99% (1) (P < 0.0001) for
      RC and CC respectively in template proforma format. CONCLUSION: A template
      proforma and surgeon's contribution in relation to operative findings improves
      the quality of the histopathology report in CRC.

PMID- 19740159
TI  - Editors' choice. Women's health in low-resource settings.

PMID- 19740160
TI  - MDG 5: how close are we to success?
AB  - Only 6 years are left until 2015, the target date for achieving the Millennium
      Development Goals (MDG), yet improving maternal health (MDG 5) continues to lag
      behind. At the global level, maternal mortality still remains high in sub-Saharan
      Africa and Southeast Asian countries. Most deaths are preventable and occur due
      to unavailability of and/or poor quality of service. Skilled care at facilities
      ensures safety, cleanliness, the availability of supplies and equipment, and it
      makes management and supervision easier. With the mixture of professionals in a
      facility, life-saving emergency care can be provided quickly. Wherever childbirth
      takes place, it is essential that the person who helps has the core competencies
      for safe delivery, has the necessary equipment and supplies, and has the option
      to refer to a functioning facility offering emergency obstetric and newborn care.
      The continuing high incidence of maternal and perinatal mortality and morbidity
      is unacceptable precisely because it is solvable. We know how to make pregnancy
      and childbirth safe. The task is enormous but not insurmountable. Our efforts of
      investment need to be equal to the tasks and must be intensified if maternal and
      perinatal morbidity and mortality is to be reduced.

PMID- 19740162
TI  - Joining the dots: a plea for precise estimates of the maternal mortality ratio in
      sub-Saharan Africa.
AB  - Monitoring of maternal mortality levels in sub-Saharan Africa (SSA) to assess the
      achievements of safe motherhood programmes and for MDG-5 has been made difficult
      because of the lack of precise estimates of the maternal mortality ratio (MMR).
      Projections based on the slow rate of decline of the MMR indicate that MDG-5 may
      not be reached before the end of this century in this region. Measurements done
      using demographical and health surveys, statistical modelling and censuses are
      imprecise and do not allow trends in individual countries to be established. SSA
      countries should be encouraged to measure mortality levels from their own
      resources, using methods that produce precise estimates such as population-based
      surveys. Establishment of the trends will lead to country-specific program
      targets. The less frequent but more precise measurements can be afforded by SSA
      countries, as a case study from Zimbabwe shows.

PMID- 19740163
TI  - Scaling up human resources for women's health.

PMID- 19740164
TI  - Building capacity for anaesthesia in low resource settings.
AB  - Direct causes of maternal deaths are responsible for about 80% of maternal
      mortality in developing regions of the world. Death from any one of these can be
      prevented by the use of relatively inexpensive, simple medical interventions
      which includes the use of anesthesia and anesthetic techniques. Lack of
      anesthetic care and anesthesia has been recognized as a limiting factor to
      successful provision of life saving interventions that could prevent maternal
      deaths in low resource settings. Doctor anesthetists are few and the anesthetic
      care has been adequately provided by non doctor anesthetist in many of these
      settings. Increasing the numbers of non doctor anesthetists and strengthening
      their capacity where they exist, is a strategy which will contribute to maternal
      mortality reduction in such settings. Several UK based organizations have
      contributed to increasing the capacity to deliver anesthesia in developing
      countries over the past 15-20 years. Learning from their experiences, a high
      level of training in anesthesia for non doctors can be introduced or existing
      programmes improved upon. This article proposes a mechanism to achieve this
      through national and international links for resource poor settings.

PMID- 19740165
TI  - Quality of care for maternal and newborn health: the neglected agenda.
AB  - The quality of care received by mothers and babies in developing countries is
      often reported as poor. Yet efforts to address this contributory factor to
      maternal and newborn mortality have received less attention compared with
      barriers of access to care. The current heightened concern to achieve Millennium
      Development Goals 4 & 5 has illuminated the neglected quality agenda. Whilst
      there is no universally-accepted definition of "quality care", it is widely
      acknowledged to embrace multiple levels--from patient to health system, and
      multiple dimensions, including safety as well as efficiency. Quality care should
      thus lie at the core of all strategies for accelerating progress towards MDG4 &5.
      Interventions to measure and improve quality need themselves to be evidence
      based. Two promising approaches are maternal and perinatal death reviews and
      criterion-based audit. These and other quality improvement tools have a crucial
      role to play in the implementation of effective maternal and newborn care.

PMID- 19740166
TI  - The role of instrumental vaginal delivery in low resource settings.

PMID- 19740167
TI  - The evolving management of the third stage of labour.
AB  - The immediate postpartum period is a risky period because life-threatening events
      can occur unexpectedly, and lead to death if they are not managed promptly.
      Appropriate management of the third stage of labour can reduce severe postpartum
      haemorrhage and death. This commentary summarizes how various management
      techniques of third stage of labour evolved to date and the evidence base for
      current international recommendations.

PMID- 19740169
TI  - Obstetric fistula--a new way forward.

PMID- 19740170
TI  - Skilled birth attendance-lessons learnt.
AB  - To reduce the horrific maternal mortality figures that we have globally
      especially in resource poor countries, there was a global commitment to reduce
      maternal mortality by three-quarters by 2015 using 1990 as a baseline. To measure
      the achievement of this goal, two indicators: maternal mortality ratio and
      proportion of births attended by skilled attendance were selected. To ensure
      skilled attendance at birth for all women, the international community set a
      target of 80% by 2005, 85% by 2010 and 90% coverage by 2015. However, in 2008
      only 65.7% of all women were attended to by a skilled attendant during pregnancy,
      childbirth and immediately postpartum globally with some countries having less
      than 20% coverage. With the global human resource crisis, achieving this target
      is challenging but possible. This paper provides a narrative review of the
      literature on the skilled birth attendance strategy identifying key challenges
      and lessons learnt.

PMID- 19740171
TI  - Ensuring effective Essential Obstetric Care in resource poor settings.
AB  - Although Emergency Obstetric Care (EOC) is globally accepted as a key strategy to
      improve maternal health and reduce maternal mortality, there is still a lot of
      debate surrounding its use--What is EOC? Is it evidence-based? How can we measure
      it? How can we improve access to EOC? This paper attempts to answer these
      questions. Although there are no randomized controlled trials, there is strong
      evidence from quasi-experimental, observational and ecological studies that EOC
      should be a critical component of any programme to reduce maternal mortality.
      This paper also identifies the barriers to accessing EOC and proposes strategies
      to overcome them which could contribute to achieving Millennium Development Goal
      5.

PMID- 19740173
TI  - Newborn survival in low resource settings--are we delivering?
AB  - The annual toll of losses resulting from poor pregnancy outcomes include half a
      million maternal deaths, more than three million stillbirths, of whom at least
      one million die during labour and 3.8 million neonatal deaths--up to half on the
      first day of life. Neonatal deaths account for an increasing proportion of child
      deaths (now 41%) and must be reduced to achieve Millennium Development Goal (MDG)
      4 for child survival. Newborn survival is also related to MDG 5 for maternal
      health as the interventions are closely linked. This article reviews current
      progress for newborn health globally, with a focus on the countries where most
      deaths occur. Three major causes of neonatal deaths (infections, complications of
      preterm birth, intrapartum-related neonatal deaths) account for almost 90% of all
      neonatal deaths. The highest impact interventions to address these causes of
      neonatal death are summarised with estimates of potential for lives saved. Two
      priority opportunities to address newborn deaths through existing maternal health
      programmes are highlighted. First, antenatal steroids are high impact, feasible
      and yet under-used in low resource settings. Second, with increasing investment
      to scale up skilled attendance and emergency obstetric care, it is important to
      include skills and equipment for simple immediate newborn care and neonatal
      resuscitation. A major gap is care during the early postnatal period for mothers
      and babies. There are promising models that have been tested mainly in research
      studies in Asia that are now being adapted and evaluated at scale including
      through a network of African implementation research trials.

PMID- 19740175
TI  - The use of misoprostol in obstetrics and gynaecology.
AB  - Misoprostol, although originally introduced as a therapy for gastric ulcers, is
      now widely used in reproductive health. For some indications it is now the
      optimal choice, whilst for others it provides an important alternative,
      especially in low-resource settings. The optimal dose varies widely from 20 to
      600 mcg depending on the indication and gestation. Use of the correct dose is
      important, too low a dose will be ineffective and overdosage can be dangerous for
      mother and baby. Evidence-based information about the safest regimens for
      multiple pregnancy indications are therefore provided in this review.

PMID- 19740177
TI  - Management of infertility in low resource countries.
AB  - Infertility is a global problem, but the highest prevalence is in low resource
      countries, particularly in sub-Saharan Africa where infection-related tubal
      damage is the commonest cause. Most infections causing tubal damage are
      preventable and assisted conception can treat the infertility. However, assisted
      conception, despite being available for nearly three decades is either
      unavailable or inaccessible to most residents of resource poor countries.
      Infertility has social, economic and personal effects, which go beyond
      childlessness, and women bear the major brunt of the burden. There is urgent need
      for a comprehensive sexual and reproductive healthcare initiative involving
      maternal and child health, safe abortions, family planning and infertility
      prevention and management. The provision of low cost assisted reproduction for
      couples in poorly resourced countries also needs to be revisited.

PMID- 19740178
TI  - Preventing mother-to-child transmission of HIV.
AB  - HIV transmission from mother-to-child remains a major cause of infant morbidity
      and mortality in resource-poor settings. There is consensus that women who need
      antiretroviral treatment should receive this during pregnancy and beyond, and
      that an appropriate antiretroviral prophylactic regimen should be given to those
      who do not yet need ongoing therapy. Infant feeding remains a major source of
      infection and new antiretroviral strategies, for mothers or children, are
      emerging with the potential to control this. Access to HIV testing and
      antiretroviral treatment or prophylaxis remain very limited in low resource
      settings and needs to be expanded.

PMID- 19740179
TI  - How to... advocate for political change on obstetrical and gynaecological issues
      facing low-income countries.

PMID- 19740180
TI  - How to... teach.

PMID- 19740181
TI  - How to...find evidence-based advice on the internet.

PMID- 19740183
TI  - How to... provide effective technical assistance.

PMID- 19740184
TI  - Working outside the lines.

PMID- 19740185
TI  - The spectrum of long-term electrophysiologic abnormalities in patients with
      univentricular hearts.
AB  - Patients with univentricular hearts experience a wide range of electrophysiolgic
      abnormalities which tend to develop years after cardiovascular surgical
      interventions. Intra-atrial reentrant tachycardia (atrial flutter) in the Fontan
      population is the most common arrhythmia and, as such, has the largest body of
      literature addressing its cause and treatment. However, sinus node dysfunction,
      other atrial arrhythmias, ventricular arrhythmias, and cardiac dysynchrony also
      occur in this patient population. The purpose of this article is to review the
      prevalence, mechanisms, and treatment of these electrophysiologic abnormalities
      within the single ventricle and Fontan patient.

PMID- 19740186
TI  - Development of a pediatric cardiology quality improvement collaborative: from
      inception to implementation. From the Joint Council on Congenital Heart Disease
      Quality Improvement Task Force.
AB  - While clinical outcomes in pediatric cardiac disease have improved in recent
      years, marked institutional and individual cardiology practice variability
      exists. Quality improvement science has demonstrated that reducing process
      variation leads to more favorable outcomes, safer practices, cost savings, and
      improved operating efficiency. This report describes the process undertaken to
      develop the first collaborative quality improvement project of the Joint Council
      on Congenital Heart Disease. The project chosen aims to reduce mortality and
      improve the quality of life of infants with hypoplastic left heart syndrome
      during the interstage period between discharge from the Norwood procedure and
      admission for the bidirectional Glenn procedure. The objective of this special
      article is to inform the pediatric cardiology and cardiac surgery communities of
      the project to help ensure that the early work by the project pilot participants
      will spread to clinicians caring for children with cardiovascular disease. It is
      anticipated that this project will add to our understanding of care for this
      challenging group of children with hypoplastic left heart syndrome, identifying
      clinical care changes with the potential to lead to improvements in outcome. It
      will also introduce the field of pediatric cardiology to the science of
      collaborative quality improvement and assist in reducing clinical process
      variation and improving patient outcomes across centers. Finally, it will
      establish an ongoing network of pediatric cardiologists and their teams linked
      through a longitudinal data set and collaboration for improvement and research.

PMID- 19740187
TI  - Standardized management improves outcomes after the Norwood procedure.
AB  - BACKGROUND: In the past decade, many advances in the care of patients undergoing
      the Norwood procedure (NP) have been reported, but management remains
      nonstandardized at many institutions. We studied the impact of a standardized
      management protocol for neonates undergoing NP. METHODS: Care of NP patients has
      been protocol-driven at our institution since 2005, with routine use of regional
      low flow perfusion; near infrared spectroscopy; phenoxybenzamine with
      cardiopulmonary bypass; delayed sternal closure; peritoneal drainage; gastrostomy
      tubes; postoperative vocal cord assessment; and a home surveillance program of
      daily weight and oxygen saturation measurement. Patients undergoing NP from 2001
      to 2004 (n = 40, group 1), in whom these interventions were only selectively
      employed, were retrospectively compared with those receiving standardized
      management from 2005 to 2007 (n = 40, group 2), with endpoints of survival in
      hospital and to stage 2 palliation (S2P). Effect of protocol elements on outcome
      was evaluated by univariate and multivariate analyses. RESULTS: Hospital survival
      (95% vs. 70%, P= .003) and survival to S2P (85% vs. 58%, P= .006) was better in
      group 2. By univariate analysis, regional low flow perfusion, gastrostomy usage,
      and near infrared spectroscopy were associated with improved hospital and
      survival to S2P. In multivariable analysis, gastrostomy usage was associated with
      improved hospital survival (P= .027) and survival to S2P (P= .049), while our
      home surveillance program was a predictor of survival to S2P (P= .016).
      CONCLUSION: Protocol-driven management of NP patients was associated with better
      hospital survival and survival to S2P. Among protocol elements, gastrostomy usage
      was linked to both improved hospital survival and survival to S2P. Home
      surveillance was associated with increased survival to S2P.

PMID- 19740189
TI  - Pregnancy-related health behavior of women with congenital heart disease: room
      for behavioral change interventions.
AB  - BACKGROUND: Pregnancy in women with congenital heart disease is associated with
      maternal and neonatal complications. In order to reduce risks for unfavorable
      outcomes, pregnant women need to adopt specific health behaviors. We investigated
      the pregnancy-related health behavior of women with congenital heart disease
      during their pregnancy. METHODS: As part of a large study on pregnancy in
      congenital heart disease in the Netherlands and Belgium, we designed a
      descriptive, retrospective study that included 137 women. Patients born between
      January 1, 1958 and December 31, 1983, who had been pregnant for at least 20
      weeks, and who were in active cardiac follow-up were eligible for inclusion.
      Patients with isolated patent foramen ovale, rheumatic heart disease, and mental
      retardation were excluded. Participants were interviewed by telephone using a
      questionnaire to retrospectively assess their health behavior during pregnancy.
      RESULTS: Most of our participants did not drink alcohol (91.1-95.6%) and did not
      smoke (91.2-93.8%) during their pregnancy. Forty to fifty percent adopted
      physical restrictions. All were followed by an obstetrician, but only 38.2-56.9%
      regularly visited a cardiologist during pregnancy. CONCLUSIONS: Health behavior
      in pregnant women with congenital heart disease is generally good. However, it
      was worrisome that only a relatively few patients received follow-up from a
      cardiologist.

PMID- 19740188
TI  - Abdominal obesity, waist circumference, body mass index, and echocardiographic
      measures in children and adolescents.
AB  - BACKGROUND: Waist circumference (WC) may predict cardiovascular risk better than
      body mass index (BMI) in adults. The relationships between WC and
      echocardiographic measurements known to predict adult cardiovascular risk have
      not yet been explored in children. OBJECTIVE: This investigation sought to
      investigate whether WC predicts echocardiographic measures of cardiac structure
      and function and whether WC is a better predictor of these outcomes than BMI. If
      associations between WC and measures of diastolic function are found, are they
      due to increased left ventricular (LV) mass and whether WC and LV mass have
      synergistic or antagonistic effects on measures of diastolic function? METHODS: A
      total of 49 clinically normal children aged 3-19 years, including 17 with
      abdominal obesity, underwent detailed echocardiographic assessment to explore the
      associations between WC and various indices of systolic and diastolic function.
      Correlations, t-tests, and linear regressions were used for statistical testing.
      Results. Compared to subjects without abdominal obesity, those with abdominal
      obesity had increased left atrial dimensions, posterior wall thickness, and left
      ventricular (LV) mass index(2.7) (P < .05 for each comparison). Those with
      abdominal obesity also had altered LV filling patterns at the septal, lateral,
      and inferior wall by Doppler tissue imaging. WC was the sole predictor of, and
      was negatively associated with, the ratios of early peak velocity/late peak
      velocity at the septum, inferior wall, and right ventricle, and these
      associations were independent of LV mass (P < .001 for each comparison). Both BMI
      and WC were independent predictors of left ventricular mass index(2.7) (P= .001
      and P= .05, respectively). CONCLUSIONS: Otherwise normal children and adolescents
      with abdominal obesity had altered left ventricular diastolic function. These
      differences were often better predicted by WC than by BMI. Our findings suggest
      the importance of considering WC in future studies of the cardiovascular impact
      of childhood obesity.

PMID- 19740190
TI  - Acute effects of single-site pacing from the left and right ventricle on
      ventricular function and ventricular-ventricular interactions in children with
      normal hearts.
AB  - OBJECTIVE: We studied, as a physiological benchmark, acute effects of right
      ventricular (RV) apical, RV outflow, and left ventricular (LV) pacing in children
      with normal cardiac function on LV and RV function and ventricular-ventricular
      interactions. DESIGN: The design of the study was a prospective, acute
      intervention. SETTING: The study was conducted in a tertiary care
      electrophysiology laboratory. Population and Methods. Seven children (mean +/-
      SD, 12 +/- 4 years) were paced after accessory pathway ablation, at baseline
      (AOO), and with atrioventricular pacing (DOO) from the RV apex, RV outflow, and
      left ventricle. OUTCOME MEASURES: Right ventricular dP/dT(max) and RV dP/dT(neg)
      (high-fidelity transducer-tipped catheters, Millar Instruments, Houston, TX,
      USA), cardiac index (Fick), blood pressure, and QRS duration were measured at
      each pacing condition. Intra- and interventricular mechanical dyssynchrony,
      systolic- and diastolic peak tissue velocities, and isovolumic acceleration were
      recorded by tissue Doppler imaging at the lateral mitral, septal, and tricuspid
      annuli at each condition. Results at each pacing condition were compared by
      repeated-measures analysis of variance. Results. Pacing prolonged QRS duration,
      causing electrical dyssynchrony (86 +/- 19 ms [baseline], 141 +/- 44 ms [RV
      apex], 121 +/- 18 ms [RV outflow], and 136 +/- 34 ms [LV], P < .01). Right
      ventricular outflow pacing caused LV intraventricular delay (63 +/- 52 vs. 12 +/-
      7 ms, P < .05). Right ventricular apical pacing caused interventricular delay (61
      +/- 29 vs. 25 +/- 18 ms, P < .05). There were no significant changes in blood
      pressure, cardiac index, RV dp/dT(max), RV dP/dT(neg), regional tissue
      velocities, or isovolumic acceleration during any of the pacing conditions,
      indicating preserved ventricular function and hemodynamics. No important
      ventricular-ventricular interactions were seen. CONCLUSIONS: In children with
      normal cardiac anatomy and function, single-site RV apical, RV outflow, and LV
      pacing induce electromechanical dyssynchrony without significantly changing
      ventricular function or hemodynamics, or adversely affecting ventricular
      ventricular interactions.

PMID- 19740191
TI  - Pulse densitometer indocyanine green dilution curves: a simple applicable and
      accurate method for determination of cardiac shunts.
AB  - OBJECTIVE: Adequate hemodynamic evaluation is crucial in the management of
      patients with congenital heart disease. Although non-invasive diagnostic tools
      have reduced the need for invasive procedures, cardiac catheterization is still
      mandatory for absolute quantification of pressures, flows and vascular
      resistances in selected patients. We therefore investigated the feasibility of a
      new technique, non-invasive pulse densitometry (PD) in patients with intracardiac
      shunts and compared its results with the established standards: cuvette
      densitometry (CD) and oximetry (OX). DESIGN: Measurement method comparison study.
      OUTCOME MEASURE: In 12 patients with intracardiac shunt, dye dilution curves,
      using both pulse and cuvette densitometry, were recorded and oximetry was
      performed. Left-to-right shunt expressed as percentage of pulmonary blood flow
      Qp, was calculated from dye dilution and oximetry. In 4 patients with atrial
      septal defect, dye dilution curves were also recorded after closure of the defect
      with a device. RESULTS: The mean difference +/- SD between the shunt derived from
      PD and CD was 2.8 +/- 10.0% of Qp, 95% confidence interval -2.5 to 8.2. (Shunt-PD
      vs. Shunt-CD was 32.3 +/- 23.9% vs. 29.5 +/- 23.9% of Qp resp., n = 16). The mean
      difference +/- SD between the shunt derived from PD and OX was 0.8 +/- 9.8% of
      Qp, 95% confidence interval -5.4 to 7.0 (Shunt-PD vs. Shunt-OX was 41.5 +/- 20.3%
      vs. 40.7 +/- 19.7% of Qp resp., n = 12). CONCLUSION: Transcutaneous recording of
      dye dilution curves with a pulse dye densitometer allows easy and accurate
      quantification of intracardiac left-to-right shunt flows over a wide range in
      both children and adults with congenital heart diseases.

PMID- 19740192
TI  - Catheter-based therapy for small preterm infants with pulmonary atresia/intact
      ventricular septum.
AB  - Catheter-based therapy is the preferred treatment for term infants with pulmonary
      atresia and intact ventricular septum without right ventricular-dependent
      coronaries, membranous atresia with patent infundibulum, and acceptable-sized
      tricuspid valve. However, in smaller preterm infants, it is more difficult to
      determine the adequacy of the tricuspid valve and right ventricle for two
      ventricle repair and there are increased procedural risks. An excellent result in
      a small preterm infant with pulmonary atresia and intact ventricular septum is
      described using the following algorithm: determination of the tricuspid/mitral
      annular ratio, right-sided catheter-based intervention, and a combination of
      transthoracic echocardiography and angiography.

PMID- 19740193
TI  - A case report of rapid progressive coarctation and severe middle aortic syndrome
      in an infant with Williams syndrome.
AB  - Williams syndrome is a genetic disorder caused by multiple contiguous gene
      deletions in chromosome 7. Presentation in early life is most often a result of
      luminal stenosis of right- and left-sided arterial vasculature. We report the
      case of a newborn infant who had a rapidly progressing diffuse form of
      arteriopathy that required two surgeries and one percutaneous balloon dilation
      within the first 2 months of her life.

PMID- 19740195
TI  - Total anomalous pulmonary venous connection in an adult: comprehensive
      multimodality evaluation.
AB  - An unusual case of total anomalous pulmonary venous connection surviving to
      adulthood without surgical correction is presented. Transthoracic
      echocardiography first led to this diagnosis and magnetic resonance imaging
      refined the anatomic diagnosis leading to successful surgical correction.

PMID- 19740194
TI  - A blue baby grows up.
AB  - This report describes the history of a 41-year-old female patient born with
      atresia of the right atrioventricular valve, hypoplasia of the right ventricle,
      an atrial septal defect, and malposed great arteries. The patient underwent
      surgical pulmonary artery banding in infancy but did not undergo corrective
      surgery due to the development of pulmonary arterial hypertension. This report
      touches on several important clinical issues that may arise when caring for the
      adult with complex palliated cyanotic congenital heart disease, including the
      development and treatment of pulmonary arterial hypertension.

PMID- 19740196
TI  - Acute ischemic cardiomyopathy after extreme emotional stress in a child.
AB  - Ischemic cardiomyopathy is rare in children. It is usually caused by congenital
      anomalies of coronary arteries, coronary anomalies after coronary artery
      transfer, or Kawasaki disease. In recent years, a new cardiac syndrome-named
      "Tako-Tsubo cardiomyopathy" for the particular shape of the end systolic
      ventricle-has been described in adults. In the absence of coronary artery
      obstruction, it mimics acute myocardial infarction with chest pain and typical
      electrocardiography changes. Emotional or physical stress usually precedes this
      cardiomyopathy. At present, this entity has only been described in adults, with a
      strong predominance in postmenopausal women. We report a case of acute ischemic
      cardiomyopathy after extreme stress in a child that may share the same
      pathophysiology.

PMID- 19740197
TI  - 5th World Congress of Pediatric Cardiology and Cardiac Surgery, Cairns Convention
      Center, Queensland, Australia--June 21-26, 2009.

PMID- 19740202
TI  - News from the Section on Cardiology and Cardiac Surgery of the American Academy
      of Pediatrics.

PMID- 19740204
TI  - Adults with cerebral palsy: a workshop to define the challenges of treating and
      preventing secondary musculoskeletal and neuromuscular complications in this
      rapidly growing population.
AB  - Although the neurological injury associated with cerebral palsy (CP) is non
      progressive, adults with the disorder often develop musculoskeletal and
      neurological symptoms, such as severe pain, chronic fatigue, and a premature
      decline in mobility and function, as they age. Little is known about how to
      manage, much less prevent, these symptoms. This paper summarizes the findings of
      a multi-disciplinary workshop, sponsored by the Cerebral Palsy International
      Research Foundation, the American Academy for Cerebral Palsy and Developmental
      Medicine, and Reaching for the Stars, convened to review current knowledge and
      begin to develop a blueprint for future research. The goals of the workshop were
      to (1) define the current incidence and prevalence of CP, (2) review the known
      complications for persons aging with CP, (3) review current understanding of
      physiological processes that may contribute to loss of function and premature
      aging in CP, (4) evaluate current treatment interventions in terms of long-term
      outcomes, (5) identify cutting-edge technologies in neurorehabilitation that may
      help prevent or treat the effects of accelerated aging for persons diagnosed with
      CP, and (6) identify strategies to ensure that individuals with CP receive
      evidence-based care as they transition from pediatric to adult-care services.

PMID- 19740205
TI  - Aging with cerebral palsy and other disabilities: personal reflections and
      recommendations.
AB  - This article describes the lived experience of one 64-year-old woman who is aging
      with cerebral palsy (CP) and other multiple disabilities. Reflections are offered
      on coping with secondary conditions and functional decline; fighting the effects
      of pain and fatigue; and managing well-meaning, but misdirected, medical advice.
      Recommendations based on the author's personal and professional experience with
      disabilities, including CP, are presented on the aging process and on preventive
      care for adults living with CP.

PMID- 19740206
TI  - Cerebral palsy and aging.
AB  - Cerebral palsy (CP), the most common major disabling motor disorder of childhood,
      is frequently thought of as a condition that affects only children. Deaths in
      children with CP, never common, have in recent years become very rare, unless the
      child is very severely and multiply disabled. Thus, virtually all children
      assigned the diagnosis of CP will survive into adulthood. Attention to the adult
      with CP has been sparse, and the evolution of the motor disorder as the
      individual moves through adolescence, young adulthood, middle age, and old age is
      not well understood. Nor do we know what happens to other functional domains,
      such as communication and eating behavior, in adults with CP. Although the brain
      injury that initially causes CP by definition does not progressively worsen
      through the lifetime, the effects of CP manifest differently throughout the
      lifespan. The aging process must inevitably interact with the motor disorder, but
      we lack systematic, large-scale follow-up studies of children with CP into
      adulthood and through adulthood with thorough assessments performed over time. In
      this paper we summarize what is known of the epidemiology of CP throughout the
      lifespan, beginning with mortality and life expectancy, then survey what is known
      of functioning, ability, and quality of life of adults with CP. We conclude by
      describing a framework for future research on CP and aging that is built around
      the World Health Organization's International Classification of Functioning,
      Disability, and Health (ICF) and suggest specific tools and approaches for
      conducting that research in a sound manner.

PMID- 19740207
TI  - Health, mortality, and wellness issues in adults with cerebral palsy.
AB  - For many years, children with cerebral palsy (CP) and their parents have been
      told that health and functional status stabilize by early adulthood. However,
      adults with CP report ongoing health conditions and aging and secondary
      conditions that are not always recognized or managed by their healthcare
      providers. There is a growing body of literature to better define the health,
      mortality, and wellness of those aging with CP. In general, adults with CP report
      good health, although health outcomes appear to be linked to the severity of CP
      and to increasing age. Studies reporting on lifespan warrant caution in
      interpretation because of biases in the survey and surveillance systems. It
      appears that lifespan of persons with CP is at or close to that of the typical
      population. The most commonly reported age-related changes and secondary
      conditions involve pain/fatigue, physical performance, and the musculoskeletal
      system. Not all adults have serious health problems, and many now recognize the
      aging process as a natural course of events. Few adults with CP engage in typical
      screening and health promotion activities due to a variety of barriers. There
      continues to be much to be learned and disseminated, in order to improve the care
      of adults with CP.

PMID- 19740208
TI  - Cerebral palsy lifetime care - four musculoskeletal conditions.
AB  - Cerebral palsy (CP) has always been considered a static condition in the
      neurological sense. Secondary and associated conditions that occur in the patient
      with CPcan progress over time and cause unwanted sequelae. This paper discusses
      four musculoskeletal conditions that present across the lifetime and can lead to
      progressive loss of function in the patient with CP. Patella alta can be
      particularly painful in the early adult years, limiting mobility particularly
      when associated with crouch gait. Adults with lower-extremity weight-bearing
      status having hip dysplasia, progressive over time, often develop pain and severe
      degenerative arthritis, with or without arthrodesis. Spondylolysis, particularly
      at the L5 S1 level, is fairly common in the ambulatory adult with diplegia and
      may, if not diagnosed early, progress to spondylolisthesis. Cervical stenosis
      appears to be more prevalent in adults with spastic quadriparesis and dystonia
      and is often associated with myelomalacia and/or radiculopathy. All four of these
      conditions may be lessened, or even prevented, with intervention and diagnosis in
      the younger years. Possible interventions and outcomes over time are discussed in
      the context of multidisciplinary team management of the individual with CP.

PMID- 19740209
TI  - Osteoporosis in adults with cerebral palsy.
AB  - Life expectancy for the 400 000 adults with cerebral palsy (CP) in the USA is
      increasing. Although there is a perception of increased fractured rate in the
      adult with CP, it has not been well studied. Low bone mineral density is found in
      more than 50% of adults with a variety of disabilities, including CP. Dual-energy
      X-ray absorptiometry scanning is commonly used to assess bone mineral density,
      but is limited by positioning and other artifacts in adults with CP. Novel
      scanning regions of interest, such as the distal femur, are not yet standardized
      in adults. Nutritional assessment and physical activity, the basis of most
      fracture prevention programs, are difficult to do in the adult with CP. A better
      understanding of the 'muscle-bone unit' physiology and its exploitation may lead
      to better treatment modifications. Clinical research trials with bisphosphonates
      (e.g. pamidronate), estrogen, selective estrogen receptor modulators, parathyroid
      hormone analogs, and growth hormone need to be targeted to the adult with CP.
      Longitudinal studies of fracture risk factors, genetic research in bone and
      neuromuscular biology, and the development of treatment surrogates for physical
      activity are additional areas of needed expertise. This could be facilitated by
      an adult CP registry and the centralization of clinical research efforts.

PMID- 19740210
TI  - The role of fitness in health and disease: status of adults with cerebral palsy.
AB  - Physical activity has significant health benefits and is positively associated
      with health-related quality of life and psychosocial functioning. Persons with
      disability are at particular risk of inactivity. For adults with cerebral palsy
      (CP), impaired health and function typically impede participation in physical
      activity, setting into motion a downward spiral of prolonged inactivity. Adults
      with CP may not be engaging in sufficient physical activity to produce the
      improvements in fitness required to experience associated health benefits.
      However, the literature related to physical activity and fitness in adults with
      CP is sparse. As more and more persons with CP lead productive lives into their
      golden years, it is imperative that the scientific community provide definitive
      information to help guide decisions related to the type and extent of fitness
      related activities most beneficial to these individuals. This information will
      facilitate development of physical training programs that promote maintenance of
      function and fitness while preventing the onset of secondary conditions. This
      presentation will address the state-of-the-science regarding physical activity
      and fitness for adults with CP and how fitness training relates to physical
      activity and health in this population. Gaps in the evidence, as well as possible
      directions for future research, will be presented.

PMID- 19740211
TI  - Muscle deficits in cerebral palsy and early loss of mobility: can we learn
      something from our elders?
AB  - Ambulant young people with cerebral palsy (CP) have reduced muscle volumes in
      their lower limbs (as low as 50% of their weight-matched typically-developing
      peers). Yet, they may complete a 'timed up-and-go' test at similar speeds to
      unaffected persons. Perhaps, these individuals are able to maintain high levels
      of function because their muscle deficits have not fallen below the threshold
      values required to perform certain motor tasks. This is consistent with data from
      studies of progressive strengthening in children with mild CP. These programmes
      improve muscular output but have limited immediate effect on functional capacity.
      Sarcopenia is responsible for much of the loss of muscle mass in the typically
      developing adult. The decline in muscle mass begins in the mid-twenties and
      occurs rapidly after the 7th decade. It is possible that the muscle deficits
      characteristic of young people with CP, coupled with the decline of muscle
      properties in adulthood, contribute to an early loss of mobility in this group.
      In the typically developing elderly, progressive strengthening is thought to
      extend mobility. Perhaps, the real value of strengthening programmes in CP is to
      improve muscular reserve in the short-term and to maintain muscle mass above
      critical thresholds in the long-term.

PMID- 19740212
TI  - The potential metabolic consequences of cerebral palsy: inferences from the
      general population and persons with spinal cord injury.
AB  - The metabolic consequences of cerebral palsy (CP) have not been reported. The
      observations and suggestions presented in this article are based on our current
      knowledge of physiology in the general population and on information on the known
      metabolic consequences of disability in persons with spinal cord injury. Because
      of pain, fatigue, and other secondary consequences of CP, adolescents with CP who
      are ambulatory may become less physically active with age. This phenomenon would
      be expected to be associated with deconditioning and adverse changes in body
      composition including atrophy of muscles and an absolute or relative increase in
      adiposity. Insulin resistance, hyperinsulinemia, and associated adverse metabolic
      changes may develop. In an unfavorable metabolic milieu, the ability of the
      pancreas to compensate for mild elevations of circulating glucose may diminish.
      The combination of reduced fitness and conventional risk factors for
      cardiovascular disease would be expected to increase the risk for coronary heart
      disease (CHD); however, there has been no assessment of the risk factors for CHD
      in adults with CP. Once subgroups with modifiable risk factors for cardiovascular
      disease have been identified, risk factors for CHD should be aggressively
      treated, according to current standards of care.

PMID- 19740213
TI  - The pathogenesis of osteoarthritis in cerebral palsy.
AB  - The morphogenesis, remodeling, and degeneration of diarthroidial joints are
      directly under the control of the loading histories created by the
      musculoskeletal system during development and aging. The altered loading
      histories in individuals with cerebral palsy (CP) lead to aberrations in joint
      morphogenesis and an acceleration of joint degeneration. To understand this
      process in the hip, the normal ontogeny of the hip joint is reviewed with special
      attention to the mechano-biological factors associated with joint morphogenesis,
      endochondral ossification, and cartilage degeneration. A contrast is then made
      with the mechano-biological alterations observed with CP and the consequent
      influence on joint destruction. The features of the pathogenesis are: (1) altered
      muscular activity and restricted range of motion result in abnormal joint
      morphology, subluxation, and poor coverage of the femoral head; (2) joint
      incongruities created in early development cause local stress concentrations that
      can mechanically damage the articular cartilage; (3) the reduced magnitudes of
      muscular forces reduce the contact pressures at the joints, creating thinner
      cartilage and osteopenia; and (4) the thinner cartilage degenerates early, and
      subchondral bone collapse further contributes to the mechanical destruction of
      the remaining cartilage.

PMID- 19740214
TI  - Surgical treatment for hip pain in the adult cerebral palsy patient.
AB  - Hip subluxation or dislocation in the cerebral palsy population is an acquired
      condition that can result in pain and limitation of function. The incidence is
      reported to be from 18 to 59%. Awareness of the factors that cause the problem
      are essential in order to prevent this condition. Early treatment consists of
      appropriate muscle lengthening or releases, varus rotation hip osteotomies and in
      some cases pelvic osteotomies to provide acetabular coverage for the femoral
      head. For painful hip subluxation or dislocation with arthrosis in the adolescent
      or adult salvage procedures such as hip arthrodesis, valgus osteotomy, proximal
      femoral resection, or total hip arthroplasty have all been done to relieve pain.
      The author recounts his experience of the surgical management of the hip in the
      individual with cerebral palsy.

PMID- 19740215
TI  - Scoliosis in cerebral palsy.
AB  - Spinal deformity is a common musculoskeletal problem for individuals with
      cerebral palsy. Severe scoliosis may impair physical function and may be a source
      of pain. Spine braces and carefully constructed seating arrangements may moderate
      the behavior of these deformities but do not seem capable of stopping
      progression, which often continues in adulthood. Spine fusion surgery can produce
      a stable, durable trunk shape that improves sitting and positioning but the
      process of surgery is arduous and outcomes can be compromised by numerous serious
      complications. Despite complications, many families and caregivers express
      satisfaction with the results of surgery. Careful patient evaluation, studious
      attention to surgical planning and performance, and a good relationship with
      patients, family members, and other providers is essential.

PMID- 19740216
TI  - Orthopaedic issues in the musculoskeletal care of adults with cerebral palsy.
AB  - AIMS: Orthopaedic care of adults with cerebral palsy (CP) has not been well
      documented in orthopaedic literature. This paper focuses on some of the common
      problems which present themselves when adults with CP seek orthopaedic
      intervention. In particular, we review the most common orthopaedic issues which
      present to the Penn Neuro-Orthopaedics Program. METHOD: A formal review of
      consecutive surgeries performed by the senior author on adults with CP was
      previously conducted. This paper focuses on the health delivery care for the
      adult with orthopaedic problems related to cerebral palsy. Ninety-two percent of
      these patients required lower extremity surgery. Forty percent had procedures
      performed on the upper extremities. RESULTS: The majority of problems seen in the
      Penn Neuro-Orthopaedics Program are associated with the residuals of childhood
      issues, particularly deformities associated with contractures. Patients are also
      referred for treatment of acquired musculoskeletal problems such as degenerative
      arthritis of the hip or knee. A combination of problems contribute most
      frequently to foot deformities and pain with weight-bearing, shoewear or both,
      most often due to equinovarus. The surgical correction of this is most often
      facilitated through a split anterior tibial tendon transfer. Posterior tibial
      transfers are rarely indicated. Residual equinus deformities contribute to a pes
      planus deformity. The split anterior tibial tendon transfer is usually combined
      with gastrocnemius-soleus recession and plantar release. Transfer of the flexor
      digitorum longus to the os calcis is done to augment the plantar flexor power.
      Rigid pes planus deformity is treated with a triple arthrodesis. Resolution of
      deformity allows for a good base for standing, improved ability to tolerate
      shoewear, and/or braces. Other recurrent or unresolved issues involve hip and
      knee contractures. Issues of lever arm dysfunction create problems with
      mechanical inefficiency. Upper extremity intervention is principally to correct
      contractures. Internal rotation and adductor tightness at the shoulder makes for
      difficult underarm hygiene and predispose a patient to a spiral fracture of the
      humerus. A tight flexor, pronation pattern is frequently noted through the elbow
      and forearm with further flexion contractures through the wrist and fingers.
      Lengthenings are more frequently performed than tendon transfers in the upper
      extremity. Arthrodesis of the wrist or on rare occasions of the metacarpal
      phalangeal joints supplement the lengthenings when needed. CONCLUSIONS: The Penn
      Neuro-Orthopaedics Program has successfully treated adults with both residual and
      acquired musculoskeletal deformities. These deformities become more critical when
      combined with degenerative changes, a relative increase in body mass, fatigue,
      and weakness associated with the aging process.

PMID- 19740217
TI  - Intrathecal baclofen use in adults with cerebral palsy.
AB  - Intrathecal baclofen (ITB) is an effective treatment for both spasticity and
      dystonia in people with cerebral palsy (CP). Its use is becoming increasingly
      common. ITB is typically associated with fewer side effects than the oral form of
      the product, but there are risks related to the hardware needed for intrathecal
      delivery. Much of what has been reported in the literature about ITB is based on
      experience with children or groups of children and adults; few reports
      exclusively address its use in adults with CP. These reports indicate that muscle
      tone is consistently reduced, but there is some variability in functional
      outcomes. Few well-controlled studies have been done. Controversies remain
      concerning ITB, including whether a trial is needed before pump implantation,
      proper catheter tip placement, and programming options, as well as whether it
      contributes to the development or progression of scoliosis. These and other
      unanswered questions should be addressed in a systematic way.

PMID- 19740218
TI  - Pain in adults with cerebral palsy: impact and solutions.
AB  - Studies of health in adults with cerebral palsy (CP) have identified pain as a
      significant concern. Investigations regarding incidence, intensity, and location
      in adults with CP found that increasing age and inactivity appeared to be related
      to pain. Activity and participation in adults with CP seem to be only moderately
      affected by presence of pain. Various sources of pain have been identified in
      adults with CP but have not been well studied. These include orthopedic issues,
      poor bone mineral density and related fractures, dental and jaw problems, and
      nutrition-related pain. Limited healthcare utilization studies suggest that
      adults with CP use healthcare services, especially preventative and
      rehabilitative services less, and do not consult physicians regarding pain.
      Medication solutions for chronic pain are not well studied. Botulinum toxin and
      intrathecal baclofen have been demonstrated to minimize pain; however, the impact
      of other medications needs further investigation. Other interventions for pain
      include small studies examining the use of biofeedback and exercise. Larger
      studies are needed to establish effectiveness. In order to prevent future
      generations of adults with CP from experiencing high levels of pain,
      environmental sources of pain need more specific study, as do interventions that
      are affordable and easily accessed.

PMID- 19740219
TI  - Complementary and alternative methods in cerebral palsy.
AB  - There are no published studies specifically addressing complementary and
      alternative treatments in adults with cerebral palsy (CP). However, national
      surveys of adults with chronic disabilities document that a majority of them use
      such treatments, that they are willing to pay out of pocket, if necessary, and
      that they believe that pursuing such treatment relieves pain, reduces stress and
      anxiety, and leads to improved feelings of fitness and well-being. Individuals
      enjoy taking charge of their own health care decisions, and frequently feel more
      in control with these therapies than with more traditional methods. In contrast
      to adults, there is some information on complementary and alternative methods
      (CAM) in children with CP. This article discusses some of the CAM used in
      children that may be carried over into adulthood, as well as the pitfalls for
      patients and conventional physicians as they try to sort out what might be
      helpful and what might be harmful in this arena. Practitioners of both
      conventional and CAM therapies believe that exercise can be beneficial;
      accordingly, activities such as recreational sports, yoga, and hippotherapy may
      be continued from childhood into adulthood. General treatments for stress and
      anxiety, through such activities as yoga and meditation, though not directed at
      CP per se, may be more popular for adults than children. Research in this area
      should first identify what methods are being utilized and then subject these
      methods to well-designed outcome studies that take into account any associated
      risks.

PMID- 19740220
TI  - Neural plasticity and treatment across the lifespan for motor deficits in
      cerebral palsy.
AB  - The past decade of research in neuroscience and stroke rehabilitation has
      demonstrated that the adult brain is capable of recovery through physiological
      processes (often called 'plasticity'). Some of the recovery is spontaneous and
      some is a result of experience, including interventions such as physical therapy,
      which probably enhance or activate changes in brain structure and function. There
      is virtually no literature on physiological changes in the brains of children or
      adults with cerebral palsy (CP) after an intervention. It is unclear whether the
      principles of plasticity that have been deduced from animal models of stroke
      might also apply to children and adults with CP. But children with CP should have
      the potential to respond to experience in a similar way to adults, with the
      additional potential of regulation of neuronal development in response to injury.
      This article describes mechanisms of plasticity and a rehabilitation strategy to
      preserve the substrates for motor control in CP and then to apply later therapies
      for more refinement of motor control.

PMID- 19740221
TI  - Motor mapping in cerebral palsy.
AB  - The measurement of motor deficits in individuals with cerebral palsy (CP) has
      been largely based on clinical criteria. Yet functional imaging and non-invasive
      stimulation methods provide a means to measure directly abnormalities of the
      motor system. The size and location of muscles and movement representations can
      be determined with transcranial magnetic stimulation (TMS) and functional
      magnetics resonance imaging. Thus the homunculus can be individually mapped in
      children with CP. Because size of representation within the homunculus relates to
      quality of motor control, measurement of the distance between body parts provides
      a metric that may be useful in classifying deficits. Bilateral motor control in
      one hemisphere, while normal in neonates, persists variably in CP, providing
      another physiological metric. In this study, we used TMS to measure hand and
      ankle representations in a convenience sample of children with spastic CP.
      Overlapping thumb and ankle maps were found in children with both hemiplegia and
      diplegia, and these maps may be from either side of the body. While more
      participants are required to make conclusions about disability and
      compression/bilaterality of the homunculus, it appears as if TMS-derived metrics
      relate to motor abnormalities. These abnormal motor maps also are a therapeutic
      target, as stimulation methods are being developed as adjuncts to physical means
      of rehabilitation.

PMID- 19740222
TI  - Robot-assisted task-specific training in cerebral palsy.
AB  - Our goal was to examine the feasibility of applying therapeutic robotics to
      children and adults with severe to moderate impairment due to cerebral palsy
      (CP). Pilot results demonstrated significant gains for both groups. These results
      suggest that robot-mediated therapy may be an effective tool to ameliorate the
      debilitating effects of CP and provide new opportunities for reducing impairment
      and improving coordination.

PMID- 19740223
TI  - Investigation of goal change to optimize upper-extremity motor performance in a
      robotic environment.
AB  - Robotic devices for therapy have the potential to enable intensive, fully
      customized home rehabilitation over extended periods for individuals with stroke
      and traumatic brain injury, thus empowering them to maximize their functional
      recovery. For robotic rehabilitation to be most effective, systems must have the
      capacity to assign performance goals to the user and to increment those goals to
      encourage performance improvement. Otherwise, individuals may plateau at an
      artificially low level of function. Frequent goal change is needed to motivate
      improvements in performance by individuals with brain injury; but because of
      entrenched habits, these individuals may avoid striving for goals that they
      perceive as becoming ever more difficult. For this reason, implicit, undetectable
      goal change (distortion) may be more effective than explicit goal change at
      optimizing the motor performance of some individuals with brain injury. This
      paper reviews a body of work that provides a basis for incorporating implicit
      goal change into a robotic rehabilitation paradigm. This work was conducted with
      individuals without disability to provide foundational knowledge for using goal
      change in a robotic environment. In addition, we compare motor performance with
      goal change to performance with no goal or with a static goal for individuals
      without brain injury. Our results show that goal change can improve motor
      performance when participants attend to visual feedback. Building on these
      preliminary results can lead to more effective robotic paradigms for the
      rehabilitation of individuals with brain injury, including individuals with
      cerebral palsy.

PMID- 19740224
TI  - Review of electrical stimulation in cerebral palsy and recommendations for future
      directions.
AB  - Electrical stimulation (ES) for treatment of neuromuscular disorders is
      introduced. Various forms of ES are defined. Characteristics of cerebral palsy
      (CP) and treatment options are given. The clinical objectives of ES for CP
      treatment are stated. A review of the literature for treatment in CP is given.
      Several common themes within the literature and limitations in prior studies are
      explored. The majority of studies have used surface stimulation, which has
      several inherent limitations. To address these limitations, implanted devices may
      be used. Implanted device systems include percutaneous stimulation systems, and
      fully implantable leaded systems. While both of these technologies have
      advantages over surface stimulation, they also have their own limitations. To
      further address the limitations of percutaneous and fully implantable leaded
      systems, the Alfred Mann Foundation has developed a completely implantable,
      telemetered device known as the Radio Frequency Microstimulator (RFM). Results
      from a study using the RFM for arm rehabilitation in poststroke patients are
      given. A list of desirable design features for an ES system for CP is given. The
      next generation microstimulator device under development at the Alfred Mann
      Foundation is presented. This device may well serve the needs for ES in CP.

PMID- 19740225
TI  - Vibration therapy.
AB  - Whole-body vibration training is a method for muscle strengthening that is
      increasingly used in a variety of clinical situations. Key descriptors of
      vibration devices include the frequency, the amplitude, and the direction of the
      vibration movement. In a typical vibration session, the user stands on the device
      in a static position or performs dynamic movements. Most authors hypothesize that
      vibrations stimulate muscle spindles and alpha-motoneurons, which initiate a
      muscle contraction. An immediate effect of a non-exhausting vibration session is
      an increase in muscle power. Most studies of the longer term use of vibration
      treatment in various disorders have pursued three therapeutic aims: increasing
      muscle strength, improving balance, and increasing bone mass. In a small pilot
      trial in children we noted improvements in standing function, lumbar spine bone
      mineral density, tibial bone mass, and calf muscle cross-sectional area.

PMID- 19740226
TI  - Transition to adult services for young people with disabilities: current evidence
      to guide future research.
AB  - This article outlines the evidence upon which best practice guidelines for
      transition to adulthood for young people with physical and developmental
      disabilities were developed in Ontario, Canada, through consensus activities.
      Evidence was gathered from published and unpublished literature and focus groups
      with young people, parents, community members, service providers and policy
      makers across the province. The evidence was then synthesized and analyzed by an
      expert panel. Guidelines were developed in the areas of collaboration, capacity
      building, information, education, and research. This article focuses on the
      findings of this project as they relate to transition services and care. These
      best practice guidelines for the transition to adulthood for young people with
      disabilities offer a starting point to encourage service providers to work
      collaboratively with young people, parents, communities, governments, and
      researchers. The evidence from this project supports a move away from purely
      service-driven models of transition to holistic, lifecourse/lifespan approaches.
      Recommendations for future study and collaborative knowledge dissemination are
      provided.

PMID- 19740227
TI  - Meeting the needs of young people and adults with childhood-onset conditions:
      Gillette Lifetime Specialty Healthcare.
AB  - This paper describes how Gillette Specialty Healthcare developed a program to
      meet the specialty-care outpatient and in-patient needs of children with cerebral
      palsy (CP) and other serious congenital disabilities as they made the transition
      to early adulthood. The program began in 2001, with the opening of a pilot clinic
      for adult outpatients. Several years later, the hospital opened a small in
      patient unit for selected patients. Careful planning, consultation with staff,
      and partnerships with caregivers were crucial to program development. Attention
      to the physical environment was also essential. Utilizing an integrative model of
      care, the patient, caregivers, and the program service providers create a
      comprehensive plan of care that reflects each patient's needs, preferences, and
      priorities. The Gillette program, when evaluated over the long term, may serve as
      a model for meeting the emerging needs of the young adult with CP.

PMID- 19740231
TI  - Women's experiences with anal sex: motivations and implications for STD
      prevention.
AB  - CONTEXT: Heterosexual anal intercourse is a highly efficient mode of HIV
      transmission, yet little is known about the contexts in which women engage in it,
      or when and with whom they use condoms. Similarly, sexuality and reproductive
      health research has paid little attention to female desire and pleasure-seeking.
      METHODS: In-depth interviews were conducted in Boston in 2006 with 28 women who
      reported having had unprotected anal intercourse in the last year with a man who
      was HIV-positive or whose serostatus was unknown. Sexual scripting theory guided
      analyses of their experiences with and motivations to practice anal intercourse.
      RESULTS: Participants engaged in anal intercourse for a wide variety of reasons:
      to experience physical pleasure, enhance emotional intimacy, please their male
      partners or avoid violence. Male partners usually initiated anal sex. Anal
      intercourse often occurred in the context of vaginal and oral sex. Among reasons
      women cited for not using condoms were familiarity with their partner and feeling
      that condoms made anal sex less pleasurable. Knowledge of HIV and STD risks did
      not appear to encourage condom use. CONCLUSIONS: Women who perceive condom use
      during anal sex as limiting their pleasure or intimacy may be at increased risk
      for acquiring HIV. Consequently, interventions to promote safer anal intercourse
      must find a way to increase the use of barrier methods without decreasing
      pleasure or perceived intimacy between sexual partners.

PMID- 19740232
TI  - Arousal loss related to safer sex and risk of pregnancy: implications for women's
      and men's sexual health.
AB  - CONTEXT: Few studies have examined arousal loss associated with safer-sex
      practices or the perceived risk of unintended pregnancy, let alone its
      associations with sexual risk practices. METHODS: An Internet survey conducted in
      2004-2006 among 2,399 men and 3,210 women asked respondents about arousal loss
      related to the use of condoms or other safer-sex products and perceived
      unintended pregnancy risk. Regression analyses gauged associations between
      arousal profiles, unprotected sex in the last year and lifetime experience of
      unintended pregnancy. RESULTS: Many respondents reported arousal loss related to
      the use of safer-sex products (34%) or the risk of unintended pregnancy (46%).
      Participants who strongly agreed that use of safer-sex products can lessen their
      arousal were significantly more likely to have had unprotected sex in the last
      year than were those who strongly disagreed (odds ratios, 1.8 for men and 3.7 for
      women); those who strongly disagreed that pregnancy risk can lessen their arousal
      were significantly more likely to have been involved in an unintended pregnancy
      than were those who strongly agreed (2.0 for men and 1.4 for women). Arousal loss
      related to safer-sex practices was more strongly associated with unprotected sex
      among women than among men, whereas arousal loss related to pregnancy risk was
      more strongly associated with unintended pregnancy among men than among women.
      CONCLUSIONS: Some men and women are turned off by safer-sex practices or by
      pregnancy risk. Given arousal profiles' potential contributions to unintended
      pregnancies and STD transmission, they should be integrated into sexual health
      behavioral models, research and programming.

PMID- 19740233
TI  - Women's perspectives on family planning service quality: an exploration of
      differences by race, ethnicity and language.
AB  - CONTEXT: Despite calls to make family planning services more responsive to the
      values, needs and preferences of clients, few studies have asked clients about
      their experiences or values, and most have used surveys framed by researchers',
      rather than clients', perspectives. METHODS: Forty in-depth interviews exploring
      lifetime experiences with and values regarding services were conducted with 18-36
      year-old women who visited family planning clinics in the San Francisco Bay Area
      in 2007. Women were categorized as black, white, English- or Spanish-speaking
      Latina, or of mixed ethnicity to allow examination of differences by racial,
      ethnic and language group. Interviews were audiotaped, transcribed and coded
      thematically; matrices were then used to compare the themes that emerged across
      the subgroups. RESULTS: Eight themes emerged as important to women's views of
      services: service accessibility, information provision, attention to client
      comfort, providers' personalization of care, service organization, providers'
      empathy, technical quality of care and providers' respect for women's autonomy.
      Women reported that it was important to feel comfortable during visits, to feel
      that their decision-making autonomy was respected, to have providers show empathy
      and be nonjudgmental, and to see the same provider across visits. The only
      notable difference among racial, ethnic and language groups was that Spanish
      speaking Latinas wanted to receive language-appropriate care and contraceptive
      information. CONCLUSIONS: Future surveys of family planning service quality
      should include measures of the factors that women value in such care, and efforts
      to improve providers' communication and counseling skills should emphasize the
      personalization of services and respect for clients' autonomy.

PMID- 19740234
TI  - Decomposing trends in nonmarital fertility among Latinas.
AB  - CONTEXT: For Latinos, high rates of nonmarital fertility reinforce economic
      inequality and slow the pace of social and economic incorporation into American
      society. METHODS: Changes in the nonmarital fertility ratio--nonmarital births as
      a percentage of all births (NMFR)--among women aged 15-44 over the period 1994
      2005 were partitioned into three components: changes in marital and in nonmarital
      fertility, and in the proportion of women who were married. Annual birth data
      were drawn from the national Natality Detail File, and population estimates were
      drawn from the Current Population Surveys. Analyses were conducted for blacks,
      whites and Latinas, as well as for selected subgroups of Latinas; differences in
      NMFRs between racial and ethnic groups were also calculated. RESULTS: NMFRs were
      largely unchanged between 1994 and 2002, and then began to rise; they averaged
      43% for Latinas, 69% for blacks and 23% for whites over the study period. In
      2005, 48% of births to Latinas were nonmarital. Most of the rise in Latinas' NMFR
      was linked to a decline in marriage. Among foreign-born Latinas, a six-percentage
      point increase in the NMFR was due mostly to a rise in nonmarital fertility and a
      decline in marital fertility, which offset the beneficial effects of a rising
      marriage rate. The difference between Latinas' and whites' NMFRs was largely
      attributed to Latinas' higher nonmarital fertility, whereas the difference
      between blacks' and whites' NMFRs was driven mostly by lower marriage rates among
      blacks. CONCLUSIONS: Efforts to reduce out-of-wedlock childbearing among Latinas
      are needed, and programs should promote healthy marriages, especially among
      foreign-born Latinas.

PMID- 19740236
TI  - An illusion of power: qualitative perspectives on abortion decision-making among
      teenage women in Sweden.
AB  - CONTEXT: Swedish law permits abortion at the request of a pregnant woman until
      the 18th week of gestation. However, the extent to which the decision is truly
      the woman's own is subject to debate; women are often influenced, directly or
      indirectly, by the attitudes of their partners, family and friends or by social
      norms. METHODS: Individual in-depth interviews about the pregnancy and the
      abortion decision were conducted 3-4 weeks postabortion with 25 women aged 16-20
      at different periods in 2003, 2005 and 2007. Interviews were audio-taped,
      transcribed verbatim and analyzed using latent content analysis. RESULTS: The
      main reasons for unplanned pregnancy were underestimation of pregnancy risk and
      inconsistent contraceptive use. Pregnancy prevention was perceived as the woman's
      responsibility. The abortion decision was accompanied by mixed emotions, and was
      seen as a natural yet difficult choice. Social norms and the negative attitudes
      of family and friends strongly influenced the decision. Partners and parents were
      regarded as the most important sources of support. After the abortion, the women
      felt pressured by contraceptive counselors to use highly effective contraceptives
      despite their previous negative experiences or worries about side effects.
      CONCLUSIONS: Swedish teenagers' basic right to decide whether to have an abortion
      may be limited by societal norms and disapproval of teenage childbearing. Given
      the perception that women are responsible for contraception, programs need to
      emphasize that pregnancy prevention is a shared responsibility; greater efforts
      to include males in prevention practices are needed.

PMID- 19740245
TI  - The introduction of MELD-based organ allocation impacts 3-month survival after
      liver transplantation by influencing pretransplant patient characteristics.

PMID- 19740247
TI  - The merits of measuring the quality of clinical trials: is it becoming a
      Byzantine discussion?

PMID- 19740237
TI  - Relationship dynamics and consistency of condom use among adolescents.
AB  - CONTEXT: Research on adolescent condom use often focuses on the influence of
      parents, peers and environmental factors. Although most sexually active teenagers
      have sex within dating relationships, little is known about associations between
      the characteristics of these relationships and consistency of condom use.
      METHODS: Data on 269 participants in Wave 1 of the Toledo Adolescent
      Relationships Study who had had sex in their current or most recent dating
      relationship were analyzed in logistic regression models to examine how positive
      and negative relationship qualities are associated with consistent condom use.
      RESULTS: Among teenagers who had had sex with their dating partner, both negative
      relationship dynamics (conflict, partner's controlling behavior, mistrust,
      jealousy, perceived partner inferiority) and positive qualities (love,
      enmeshment, salience, self-disclosure) were negatively associated with consistent
      condom use (odds ratios, 0.7-0.9). Asymmetries in partners' age, race and school
      were not related to consistent condom use. Relationship duration was negatively
      associated with consistency (0.98-0.99), but the association was explained by
      feelings of relationship importance. Findings for relationship qualities were
      similar for males and females, with the exception of conflict, which was
      positively associated with consistent condom use among females but not males.
      CONCLUSIONS: Although the relationship processes associated with consistent
      condom use are complex, such processes appeared to be more strongly associated
      with consistent condom use than were social and demographic characteristics.
      Programs should focus on relationship qualities and dynamics, recognizing that
      both negative and positive relationship features are associated with consistent
      condom use.

PMID- 19740248
TI  - Associations of fluoride intake with children's bone measures at age 11.
AB  - BACKGROUND: Relationships between fluoride intake and bone health continue to be
      of interest, as previous studies show conflicting results. OBJECTIVES: The
      purpose is to report associations of fluoride intake with bone measures at age
      11. METHODS: Subjects have been participating in the ongoing Iowa Fluoride
      Study/Iowa Bone Development Study. Mothers were recruited postpartum during 1992
      95 from eight Iowa hospitals, and detailed fluoride questionnaires were sent
      every 1.5-6 months. From these, combined fluoride intakes from water sources
      (home, childcare, filtered, bottled), other beverages, selected foods, dietary
      fluoride supplements and dentifrice were estimated at individual points and
      cumulatively [with area under the curve (AUC)]. Subjects underwent dual-energy X
      ray absorptiometry (DXA) scans of proximal femur (hip), lumbar spine and whole
      body (Hologic QDR 4500A). DXA results (bone mineral content - BMC; bone mineral
      density - BMD) were related to fluoride intake as revealed by bivariate and
      multivariable analyses. RESULTS: The mean fluoride intake estimated by AUC was
      0.68 mg (SD = 0.27) per day from birth to 11 years. Associations (Spearman)
      between daily fluoride intake (mg F/day) and DXA bone measures were weak (r = 
      0.01 to 0.24 for girls and 0.04 to 0.24 for boys). In gender-stratified, and body
      size- and Tanner stage-adjusted linear regression analyses, associations between
      girls' bone outcomes and fluoride intake for girls were almost all negative;
      associations for boys were all positive and none was statistically significant
      when using an alpha = 0.01 criterion. CONCLUSIONS: Longitudinal fluoride intake
      at levels of intake typical in the United States is only weakly associated with
      BMC or BMD in boys and girls at age 11. Additional research is warranted to
      better understand possible gender- and age-specific effects of fluoride intake on
      bone development.

PMID- 19740249
TI  - Development and evaluation of an oral health literacy instrument for adults.
AB  - OBJECTIVES: To develop and validate an instrument to measure the functional oral
      health literacy of adults. METHODS: For the generation of items different dental
      patient educational materials and text types were selected that had reading
      levels similar to materials used for the Test of Functional Health Literacy in
      Adults (TOFHLA) which was the model for our Oral Health Literacy Instrument
      (OHLI). The OHLI contains reading comprehension and numeracy sections. The
      reading comprehension section is a 38-item test with words omitted from one
      passage on dental caries and another on periodontal disease. The numeracy section
      has 19 items to test comprehension of directions for taking common prescriptions
      associated with dental treatment, postextraction instructions and dental
      appointments. We also developed a 17-item oral health knowledge test. The OHLI,
      the TOFHLA, the oral health knowledge test and a brief questionnaire were
      administered to a convenience sample of 100 patients. Internal reliability of
      OHLI was assessed with Cronbach's alpha. Test-retest reliability was examined by
      intra-class correlation coefficient (ICC). Concurrent validity was tested by
      comparing OHLI scores across categories of education level and frequency of
      dental visits. Construct validity was assessed by correlating OHLI scores with
      TOFHLA scores and with the oral health knowledge scores using Spearman's rho
      (rho) and multiple linear regression. RESULTS: Participants averaged 39 years (SD
      = 12.4); 73% were female; 64% had college/university education; 40% visited a
      dentist every 3-6 months. Total OHLI and TOFHLA weighted mean scores were 87.2
      and 91.7, respectively (possible range 0-100). The Cronbach's alpha values were
      high (>0.7) for OHLI and its components. The ICC values indicated good agreement
      between the test and retest results for OHLI and the oral health knowledge test.
      Patients visiting a dentist every 3-6 months had significantly higher levels of
      oral health literacy than those visiting only when they felt pain. The
      association between OHLI and education level was not significant. OHLI scores
      were significantly correlated with the scores on the TOFHLA (rho = 0.613) and the
      test of oral health knowledge (rho = 0.573). These associations remained
      significant in multiple regression models. CONCLUSION: Initial testing of OHLI
      suggested that it is a valid and reliable instrument to evaluate oral health
      literacy among adults, although additional work is needed to investigate the
      instrument's predictive validity and sensitivity to change using oral health
      outcomes with population groups known to be at high risk of low functional oral
      health literacy.

PMID- 19740252
TI  - Impact factor and its role in academic promotion.

PMID- 19740253
TI  - Lost in translation; from animal models of pulmonary fibrosis to human disease.

PMID- 19740255
TI  - Diagnosing fibrotic lung disease: when is high-resolution computed tomography
      sufficient to make a diagnosis of idiopathic pulmonary fibrosis?
AB  - Idiopathic pulmonary fibrosis (IPF), a progressive and fatal diffuse parenchymal
      lung disease, is defined pathologically by the pattern of usual interstitial
      pneumonia (UIP). Unfortunately, a surgical lung biopsy cannot be performed in all
      patients due to comorbidities that may significantly increase the morbidity and
      mortality of the procedure. High-resolution computed tomography (HRCT) has been
      put forth as a surrogate to recognize pathological UIP. The quality of the HRCT
      impacts the ability to make a diagnosis of UIP and varies based on the centre
      performing the study and patient factors. The evaluation of the HRCT includes
      assessing the distribution and predominance of key radiographical findings, such
      as honeycomb, septal thickening, traction bronchiectasis and ground glass
      attenuation lesions. The combination of the pattern and distribution is what
      leads to a diagnosis and associated confidence level. HRCT features of definite
      UIP (subpleural, basal predominant honeycomb with septal thickening, traction
      bronchiectasis and ground glass attenuation lesions) have a high specificity for
      the UIP pathological pattern. In such cases, surgical lung biopsy can be avoided.
      There are caveats to using the HRCT to diagnose IPF in isolation as a variety of
      chronic pulmonary interstitial diseases may progress to a UIP pattern. Referral
      centres with experience in diffuse parenchymal lung disease that have
      multidisciplinary teams encompassing clinicians, radiologists and pathologists
      have the highest level of agreement in diagnosing IPF.

PMID- 19740256
TI  - Management of complications from diagnostic and interventional bronchoscopy.
AB  - From the humble beginnings as a mere curiosity, the art of bronchoscopy has
      progressed at a rapid pace. The millennium ushers in new technologies and
      refinements in established techniques to facilitate early detection of cancer,
      precise targeting of pulmonary nodules and infiltrates, near-total staging of the
      mediastinum with combined endoscopic modalities and more effective palliation of
      inoperable tumours. Bronchoscopists are faced with an increasing myriad of tools
      and equipment, each promising to carry out better than the previous. It is
      opportune to review the complications of established bronchoscopic techniques and
      how to manage them as well as new complications associated with novel
      technologies. In this article, we provide a concise overview of diagnostic and
      therapeutic bronchoscopic modalities, discussion of associated complications and
      their management strategies.

PMID- 19740257
TI  - The current role of thoracic surgery in tuberculosis management.
AB  - Although tuberculosis is mainly managed medically today, thoracic surgery
      continues to play a key role in its diagnosis and treatment in selected subgroups
      of patients. In certain scenarios such as multi-drug-resistant tuberculosis,
      advanced tuberculous empyema and symptomatic bronchial stenosis, modern thoracic
      surgery may represent the only effective means of management in selected
      patients. Advances in thoracic surgery in recent years, in particular the use of
      Video-Assisted Thoracic Surgery, not only reduce postoperative morbidity for
      individual patients, but may potentially allow a wider range of tuberculosis
      patients to benefit from surgery. Respiratory physicians and thoracic surgeons
      should continue to work together to ensure that tuberculosis patients who may
      benefit from surgery are identified for prompt and effective intervention.

PMID- 19740254
TI  - Determinants of initiation and progression of idiopathic pulmonary fibrosis.
AB  - IPF is a devastating disease with few therapeutic options. The precise aetiology
      of IPF remains elusive. However, our understanding of the pathologic processes
      involved in the initiation and progression of this disease is improving. Data on
      the mechanisms underlying IPF have been generated from epidemiologic
      investigations as well as cellular and molecular studies of human tissues.
      Although no perfect animal model of human IPF exists, pre-clinical animal studies
      have helped define pathways which are likely important in human disease.
      Epithelial injury, fibroblast activation and repetitive cycles of injury and
      abnormal repair are almost certainly key events. Factors which have been
      associated with initiation and/or progression of IPF include viral infections,
      abnormal cytokine, chemokine and growth factor production, oxidant stress,
      autoimmunity, inhalational of toxicants and gastro-oesophageal reflux disease.
      Furthermore, recent evidence identifies a role for a variety of genetic and
      epigenetic abnormalities ranging from mutations in surfactant protein C to
      abnormalities in telomere length and telomerase activity. The challenge remains
      to identify additional inciting agents and key dysregulated pathways that lead to
      disease progression so that we can develop targeted therapies to treat or prevent
      this serious disease.

PMID- 19740258
TI  - Rolipram attenuates bleomycin A5-induced pulmonary fibrosis in rats.
AB  - BACKGROUND AND OBJECTIVE: Pulmonary fibrosis has a poor prognosis. The
      pathogenesis of fibrotic disorders is unclear, but the extent of lung damage due
      to persistent inflammation is regarded as a critical factor. Rolipram inhibits
      inflammation induced by various stimuli, as well as the chemotaxis of
      fibroblasts. In this study rolipram was used to treat pulmonary fibrosis induced
      by bleomycin A5 in rats, and the possible mechanisms were investigated. METHODS:
      Rolipram (0.25 mg/kg) was administered intraperitoneally daily, following
      intratracheal instillation of bleomycin A5 (5 mg/kg). Animals were killed at 7 or
      28 days after bleomycin A5 instillation, and indices of lung damage and fibrosis
      were evaluated. RESULTS: Bleomycin A5 induced pulmonary inflammation and
      fibrosis, increased the levels of malondialdehyde and tumour necrosis factor
      alpha and enhanced accumulation of collagen in the lungs. Rolipram administration
      significantly attenuated these effects. CONCLUSIONS: Rolipram ameliorated
      pulmonary inflammation and fibrosis induced by bleomycin A5 in rats. The effects
      of rolipram may be associated with its antioxidant activity and inhibition of
      tumour necrosis factor-alpha production.

PMID- 19740259
TI  - Dose-response relationship of inhaled corticosteroids and cataracts: a systematic
      review and meta-analysis.
AB  - BACKGROUND AND OBJECTIVE: The risk of cataracts associated with the long-term use
      of inhaled corticosteroids (ICS) is poorly recognized, yet may be of major public
      health importance. The aim of this study was to determine the dose-response
      relationship of ICS use and risk of cataracts in adults. METHODS: A systematic
      review and meta-analysis was performed of case-control studies of cataracts and
      ICS use, which included at least two doses of ICS and in which the number of
      cases and controls using each dose of ICS was reported. The primary outcome
      variable was risk of cataracts. RESULTS: Four case-control studies were
      identified, with a total of 46 638 cases and 146 378 controls. There was a
      significant relationship between the risk of cataracts and ICS dose, with a
      random effects pooled odds ratio for risk of cataracts per 1000 microg increase
      in daily beclomethasone dipropionate dose of 1.25 (95% CI: 1.14-1.37).
      CONCLUSIONS: The risk of cataracts was increased by approximately 25% for each
      1000 microg per day increase in the dose of beclomethasone dipropionate or
      equivalent. These findings reinforce the importance of prescribing within the
      therapeutic dose-response range for ICS in asthma and the need to determine the
      dose-response relationship for the efficacy of ICS in COPD. Screening for the
      presence of cataracts could usefully be undertaken in older subjects with asthma
      and COPD, particularly current or ex-smokers.

PMID- 19740260
TI  - Correlation between serum biomarkers and BODE index in patients with stable COPD.
AB  - BACKGROUND AND OBJECTIVE: The BODE index, based on BMI, obstructive ventilatory
      impairment, dyspnoea scale and exercise capacity, has been used to evaluate the
      severity of patients with COPD. However, the correlations between serum
      biomarkers and the BODE index in patients with stable COPD are not widely
      studied. This study evaluated potential serum biomarkers for their ability to
      identify smokers with COPD and reflect disease severity. METHODS: A comparative
      study was conducted of 100 clinically stable COPD patients and 50 matched healthy
      smokers and the difference in levels of biomarkers between the COPD patients and
      healthy smokers was measured. Serum inflammatory mediators measured were growth
      related oncogene-alpha (GRO-alpha), IL-8, tumour necrosis factor-alpha (TNF
      alpha), matrix metalloproteinase-9 (MMP-9) and monocyte chemoattractant protein-1
      (MCP-1). Variables included age, pack-years, current or ex-smoker status, inhaler
      or oral steroid use and BODE index components, including airflow obstruction, the
      distance walked in 6MWD, modified Medical Research Council (MMRC) dyspnoea scale
      and BMI. The association between serum biomarkers and the components of the BODE
      index was assessed in the COPD patients. RESULTS: The level of serum MCP-1 was
      significantly different between the COPD group and the healthy smoker group (P =
      0.003). Significant results in univariate and multivariate analysis of the
      association between biomarkers and BODE components were: serum MCP-1 correlated
      with FEV(1)% and 6MWD; serum IL-8 and GRO-alpha correlated with steroid use;
      serum TNF-alpha correlated with steroid use and FEV(1)%; and serum MMP-9
      correlated with MMRC dyspnoea scale. CONCLUSIONS: No single specific serum
      inflammatory mediator was completely correlated with BODE variable parameters in
      patients with stable COPD. Serum MCP-1 may be an important biomarker for
      identifying COPD subjects from healthy smokers and classifying COPD severity.

PMID- 19740261
TI  - Congenital lung malformation: evaluation of prenatal and postnatal radiological
      findings.
AB  - BACKGROUND AND OBJECTIVE: This study evaluated the accuracy of prenatal MRI and
      postnatal CT imaging in the identification of congenital cystic adenomatoid
      malformation and bronchopulmonary sequestration by comparison with histological
      analysis. METHODS: Over a 3-year period, 15 patients with lung malformations
      diagnosed prenatally by ultrasound were referred for prenatal MRI, and all were
      investigated postnatally by chest CT. All asymptomatic newborns with unresolved
      lesions underwent elective surgery by thoracoscopy. All surgical specimens were
      analysed histologically. RESULTS: Among the 15 patients with an abnormality
      diagnosed by ultrasound, prenatal MRI findings differed from the final
      histological diagnosis with respect to extent (n = 3), type of lesion (n = 1) and
      aberrant vessel identification (n = 4). Postnatal chest CT failed to visualize
      the aberrant vessel in one patient. Complete regression of the lesion was noted
      in two patients with bronchopulmonary sequestration, and in one patient with
      congenital cystic adenomatoid malformation and was confirmed by CT. Elective
      thoracoscopic lobectomy of the affected lobe was performed for 12 patients. Two
      conversions to thoracotomy were required. All operated patients had an uneventful
      hospital course. CONCLUSIONS: Prenatal MRI is less accurate than postnatal CT
      scan, which remains the most reliable diagnostic modality to specify the location
      and extent and kind of lesions.

PMID- 19740262
TI  - Acidosis and raised norepinephrine levels are associated with exercise dyspnoea
      in idiopathic pulmonary fibrosis.
AB  - BACKGROUND AND OBJECTIVE: Exertional dyspnoea limits patients with IPF in their
      activities of daily living. The mechanism, however, has not been elucidated. This
      study tested the hypothesis in IPF that exertional dyspnoea correlates with
      cardiopulmonary exercise responses, specifically changes in arterial blood pH and
      plasma norepinephrine (NE). METHODS: Cardiopulmonary exercise testing with
      measurements of dyspnoea (Borg scale), plasma NE, plasma lactate and arterial
      blood gases were performed in 29 patients with IPF and in nine controls. RESULTS:
      Both groups showed obvious break points in dyspnoea changes during exercise. In
      IPF, an abrupt change in the Borg scale, pH, PaCO(2) and plasma NE occurred in
      the late exercise phase after the 'break point'. Compared with controls, patients
      with IPF had significantly higher HCO(3)(-) levels and physiologic dead
      space/tidal volume during exercise. In IPF, during both exercise phases, the
      dyspnoea slope (DeltaBorg scale/Deltaminute ventilation) correlated with the pH
      slope (DeltapH/Deltaoxygen uptake) (before the break point: r = -0.537, P =
      0.0022; r = -0.886, P < 0.0001, after the break point) and the NE slope
      (DeltaNE/Deltaoxygen uptake) (before the break point: r = 0.481, P = 0.0075; R =
      0.784, P < 0.0001, after the break point). CONCLUSIONS: In patients with IPF,
      exercise-induced acidosis and increases in circulating NE levels were associated
      with intensity of exertional dyspnoea.

PMID- 19740263
TI  - Resistance and reactance in oscillation lung function reflect basal lung function
      and bronchial hyperresponsiveness respectively.
AB  - BACKGROUND AND OBJECTIVE: Currently there are few data available regarding the
      use of impulse oscillometry parameters to assess airflow obstruction during
      standardized methacholine challenge testing. METHODS: Methacholine challenge
      tests were performed using impulse oscillometry and conventional spirometry in 64
      healthy and 39 asthmatic children, in order to determine airway resistance (R)
      and reactance (X) at frequencies of 5-35 Hz, as well as FEV(1). RESULTS: Baseline
      R and X were significantly different between the healthy and asthmatic children,
      with the most discriminating parameter being resistance at 5 Hz (R5). In
      asthmatic children BHR was well demonstrated by FEV(1), X5 and X10, but not by
      R5. However, when the actual R5 values obtained in this study were compared with
      the predicted values, there appeared to be differences in the lung function
      measures that corresponded to varying methacholine concentrations. In addition,
      the PC20_FEV(1) and PC70_X5 were significantly more sensitive than other
      parameters for methacholine challenge testing. CONCLUSIONS: Measuring resistance
      at 5 Hz using impulse oscillometry facilitates significant differentiation of
      baseline lung function between asthmatic and healthy children. Additionally, X
      may be a suitable replacement for PC20 in methacholine challenge testing.

PMID- 19740264
TI  - Clinical significance of non-diagnostic pathology results from percutaneous
      transthoracic needle lung biopsy: experience of a tertiary hospital without an on
      site cytopathologist.
AB  - BACKGROUND AND OBJECTIVE: More non-diagnostic pathology results may be reported
      following transthoracic needle lung biopsy (TTNB) when no on-site cytopathologist
      is available. This study was conducted to analyse the final outcomes in patients
      with non-diagnostic pathology results, and the factors related to the adequacy of
      specimens. METHODS: The medical records of consecutive patients who had undergone
      TTNB from January 2004 to January 2005 were retrospectively analysed. Non
      diagnostic pathology results were classified into three groups: (i) atypical
      cells, (ii) non-specific inflammation and (iii) inadequate specimen. The final
      diagnosis and clinical outcome for each patient were analysed after additional
      diagnostic studies and clinical follow up. RESULTS: TTNB was performed on 291
      patients. Specimens were adequate in 256 cases. The results were non-diagnostic
      for 103 patients, and the percentages of atypical cells, non-specific
      inflammation and inadequate specimen were 15.5% (16/103), 50.5% (52/103) and 40%
      (35/103), respectively. In 14 patients (87.5%) the diagnosis of atypical cells
      was confirmed, and in 10 (62.5%) these were due to malignancies. In two patients
      (3.8%) the lesions reported as non-specific inflammation were eventually
      confirmed as malignancies. After repeated attempts to confirm their diagnoses, 22
      patients (62.9%) with initial reports of inadequate specimen were diagnosed with
      specific diseases. Specimen adequacy correlated with technical skill, size of the
      lesion, guidance method and biopsy method. CONCLUSIONS: Non-diagnostic pathology
      results from TTNB, in the absence of an on-site cytopathologist, are of value in
      assessing the clinical probability of malignancy and can be useful in the
      management of lung lesions. However, many other factors should be considered in
      patients with inadequate specimens.

PMID- 19740265
TI  - Multi-centre research in Australia: analysis of a recent National Health and
      Medical Research Council-funded project.
AB  - BACKGROUND AND OBJECTIVE: Human research ethics committees provide essential
      review of research projects to ensure the ethical conduct of human research.
      Several recent reports have highlighted a complex process for successful
      application for human research ethics committee approval, particularly for multi
      centre studies. Limited resources are available for the execution of human
      clinical research in Australia and around the world. METHODS: This report
      overviews the process of ethics approval for a National Health and Medical
      Research Council-funded multi-centre study in Australia, focussing on the time
      and resource implications of such applications in 2007 and 2008. RESULTS:
      Applications were submitted to 16 hospital and two university human research
      ethics committees. The total time to gain final approval from each committee
      ranged between 13 and 77 days (median = 46 days); the entire process took 16
      months to complete and the research officer's time was estimated to cost $A34
      143. CONCLUSIONS: Obstacles to timely human research ethics committee approval
      are reviewed, including recent, planned and potential initiatives that could
      improve the ethics approval of multi-centre research.

PMID- 19740266
TI  - High-riding superior pericardial recess: a pitfall in the upper mediastinum.
AB  - The high-riding superior pericardial recess is an anatomical entity both
      radiologists and respiratory physicians should be aware of. Recognition that this
      high-riding portion of the recess is of water attenuation, that it connects to
      the inferior portion of the superior pericardial recess, and that it does not
      exert mass effect on adjacent structures should help avert misdiagnosis and
      subsequent inappropriate treatment.

PMID- 19740267
TI  - Congenital cystic adenomatoid malformation of the lung: hazards of delayed
      diagnosis.
AB  - Congenital cystic adenomatoid malformation is a rare pulmonary developmental
      anomaly, which typically manifests in neonates and infants. Presentation in
      adulthood is uncommon, with <60 cases reported in the literature. The majority of
      cases involve one lobe only. We report a case of type 1 congenital cystic
      adenomatoid malformation in an adult presenting with a respiratory tract
      infection and haemoptysis. At thoracotomy, complex cystic masses were noted in
      the right upper and lower lobes. Lung-sparing surgery, in the form of two
      segmentectomies and a non-anatomical resection, was performed in order to avoid
      pneumonectomy. Such presentations may be problematic as potentially incomplete
      resections may increase the risk of complications and malignant transformation.
      This suggests the importance of appropriate clinical and radiological follow up.

PMID- 19740268
TI  - Bronchial anthracostenosis with mediastinal fibrosis associated with long-term
      wood-smoke exposure.
AB  - Bronchial anthracostenosis describes a disease entity consisting of bronchial
      destruction, deformity and stenosis related to dark pigmentation on bronchoscopy
      in patients with a history of coal workers' pneumoconiosis or chronic exposure to
      biomass smoke. The combined occurrence of bronchial anthracostenosis and
      mediastinal fibrosis in association with wood-smoke exposure has not been
      previously reported. This case report describes a non-cigarette smoking elderly
      woman who developed bronchial anthracostenosis and mediastinal fibrosis after
      long-term exposure to wood smoke. Clinical and radiological improvements were
      achieved after treatment with corticosteroid and tamoxifen. Awareness of this
      unusual entity will help to avoid misdiagnosis of malignancy or unnecessary
      thoracotomy.

PMID- 19740269
TI  - Endobronchial extension of granulomatous lymphadenitis in an HIV-positive man
      with immune reconstitution syndrome.
AB  - Endobronchial granuloma is a rare manifestation of endobronchial tuberculosis
      (TB). This case report describes a patient with endobronchial granuloma due to
      contiguous extension of granulomatous mediastinal lymph node inflammation,
      occurring following commencement of highly active anti-retroviral therapy in an
      HIV-positive man. Bronchoscopic findings mirrored CT imaging of endobronchial
      involvement of sub-carinal lymphadenopathy. Microbiologic studies were negative
      for acid-fast bacilli, fungal elements and malignancy. Mycobacterial and fungal
      culture as well as PCR for TB were all negative. Empiric anti-tuberculous therapy
      was commenced with complete resolution of symptoms. Immune reconstitution
      syndrome with development of active TB is common in patients commencing highly
      active retroviral therapy. Lymphadenitis is the commonest manifestation of this,
      and 20% of patients are culture negative for mycobacteria. Endobronchial
      granulomata due to TB are rare and no specific endobronchial therapy is required
      in such disease.

PMID- 19740270
TI  - Intrathecal therapy: what has changed with the introduction of ziconotide.
AB  - Administering drugs into the intrathecal space is becoming more popular in the
      treatment of patients with intractable pain or intolerable side effects of
      systemic analgesic treatments. Although morphine and ziconotide are the only
      intrathecal analgesics currently approved by regulatory authorities in the U.S.
      (Food and Drug Administration) and Europe (national-level approval by individual
      countries for morphine and European Agency for the Evaluation of Medicinal
      Products approval for ziconotide), a wide variety of opioid and non-opioid drugs
      are being used in this way. There is no official guidance concerning the
      selection of these drugs or their use in combinations and a paucity of efficacy
      and safety data from randomized controlled trials. The polyanalgesic initiative
      aims to summarize the current knowledge and to facilitate rational choices of
      intrathecal drug and drug combinations for the management of chronic pain. The
      most recent polyanalgesic consensus recommendations were published in 2007. In
      this review, we shall examine these recommendations, which are tailored toward
      those practicing intrathecal analgesia in the U.S., and discuss how they should
      be implemented in Europe, where the healthcare systems and regulations of the
      medical authorities are different.

PMID- 19740271
TI  - Continuous pain score meter.

PMID- 19740272
TI  - Spinal cord stimulation for control of low back pain after multiple corrective
      surgeries for severe scoliosis: report of a case.

PMID- 19740273
TI  - Low-dose ketamine as an adjunct to routine pain practice: are we ready yet?

PMID- 19740274
TI  - Introduction to a Virtual Special Issue: probing the carbon cycle with (13)C.

PMID- 19740275
TI  - Root carbon flux: measurements versus mechanisms.

PMID- 19740276
TI  - Horsetails get the wind up.

PMID- 19740277
TI  - An interdisciplinary look at legumes and their bacterial symbionts: some thoughts
      from Big Sky.

PMID- 19740278
TI  - Through the eye of the needle: a review of isotope approaches to quantify
      microbial processes mediating soil carbon balance.
AB  - For soils in carbon balance, losses of soil carbon from biological activity are
      balanced by organic inputs from vegetation. Perturbations, such as climate or
      land use change, have the potential to disrupt this balance and alter soil
      atmosphere carbon exchanges. As the quantification of soil organic matter stocks
      is an insensitive means of detecting changes, certainly over short timescales,
      there is a need to apply methods that facilitate a quantitative understanding of
      the biological processes underlying soil carbon balance. We outline the processes
      by which plant carbon enters the soil and critically evaluate isotopic methods to
      quantify them. Then, we consider the balancing CO(2) flux from soil and detail
      the importance of partitioning the sources of this flux into those from recent
      plant assimilate and those from native soil organic matter. Finally, we consider
      the interactions between the inputs of carbon to soil and the losses from soil
      mediated by biological activity. We emphasize the key functional role of the
      microbiota in the concurrent processing of carbon from recent plant inputs and
      native soil organic matter. We conclude that quantitative isotope labelling and
      partitioning methods, coupled to those for the quantification of microbial
      community substrate use, offer the potential to resolve the functioning of the
      microbial control point of soil carbon balance in unprecedented detail.

PMID- 19740282
TI  - Efficacy, feasibility, and pitfalls of transseptal approach in beating-heart
      mitral valve surgery.
AB  - BACKGROUND: Mitral valve surgery can be performed through the trans-atrial or the
      trans-septal approach. Although the trans-atrial is the preferred method, the
      trans-septal approach has also been used recently and has a particular value in
      beating-heart mitral valve surgery. Herein we report our experience with beating
      heart mitral valve surgery via trans-septal approach, and discuss its advantages
      and pitfalls. METHODS: Between 2000 and 2007, 214 patients underwent mitral valve
      procedures using the beating-heart surgical approach. RESULTS: One hundred and
      forty-three patients (66.8%) had mitral valve replacement, 68 patients (31.7%)
      mitral valve repair, and 82 patients (38.3%) concomitant valve procedures.
      Coronary artery bypass grafting was simultaneously performed in 30 (14%)
      patients. Thirty-day mortality was 7.4%, reoperation for bleeding 7%, stroke
      0.4%, and myocardial infarction 0.4%, and failed mitral valve repair 0.9%.
      CONCLUSION: Our experience suggests that beating-heart mitral valve surgery is
      facilitated by using the trans-septal approach.

PMID- 19740283
TI  - Impact of apex-sparing partial left ventriculectomy on left ventricular geometry,
      function, and long-term survival of patients with end-stage dilated
      cardiomyopathy.
AB  - BACKGROUND AND AIM: Currently, partial left ventriculectomy (PLV) has not been
      widely accepted as a treatment option for dilated cardiomyopathy (DCM) because
      its results thus far have been inconsistent. In an animal study, apex-sparing PLV
      (AS-PLV) was shown to produce greater improvement in left ventricle (LV) function
      than conventional PLV in which the apex was removed. The aim of this study is to
      investigate the effectiveness of AS-PLV in a clinical setting. PATIENTS AND
      METHODS: From September 1999 to December 2007, 13 patients with DCM underwent AS
      PLV. Left ventriculotomy was made in the thinnest portion of the lateral wall
      without injuring the apex, the papillary muscles, and the circumflex coronary
      artery, which supplies the neighboring myocardium. RESULTS: All patients were
      discharged from the hospital, except for one patient who developed refractory
      ventricular fibrillation on postoperative day 35. After AS-PLV, the LV diastolic
      dimension decreased from 71 +/- 10 mm to 55 +/- 9 mm; LV ejection fraction (EF)
      from 28%+/- 8% to 39%+/- 11%; and New York Heart Association (NYHA) class from 3
      +/- 1.7 to 1.5 +/- 0.6; the differences were significant (p < 0.01). LV function
      and geometry remained unchanged 2 years after AS-PLV with LVDD of 60 +/- 7 mm,
      LVEF of 34%+/- 8%, and NYHA class of 1.7 +/- 0.6, respectively (N.S vs. at
      discharge). CONCLUSIONS: Regardless of the etiology of LV dilatation, AS-PLV
      restored the ellipsoidal shape of the LV and improved LV function. AS-PLV is a
      feasible option for treating diseased LVs with lateral wall lesions.

PMID- 19740284
TI  - Chest tube selection in cardiac and thoracic surgery: a survey of chest tube
      related complications and their management.
AB  - BACKGROUND: Blood accumulating inside chest cavities can lead to serious
      complications if it is not drained properly. Because life-threatening conditions
      can result from chest tube occlusion after thoracic surgery, large-bore tubes are
      generally employed to optimize patency. AIMS: The aim of this study was to better
      define problems with current paradigms for chest drainage. MATERIALS AND METHODS:
      A survey was conducted of North American cardiothoracic surgeons and specialty
      cardiac surgery nurses. A total of 108 surgeons and 108 nurses responded.
      RESULTS: The survey revealed that clogging leading to chest-tube dysfunction is a
      major concern when choosing tube size. Of surgeons responding, 106 of 106 (100%)
      had observed chest tube clogging, and 93 of 106 (87%) reported adverse patient
      outcomes from a clogged tube. Despite techniques such as tube stripping, tapping,
      and squeezing, up to 51% of surveyed surgeons stated they are not satisfied with
      currently available tubes and procedures to avoid tube occlusion and some even
      forbid the stripping maneuver for fear of causing more bleeding by the negative
      pressures generated. In addition, respondents noted that patients experience
      increasing discomfort with increasing drain size. DISCUSSION: The major reason
      surgeons choose large-diameter chest tubes is linked to concern about the
      suboptimal available methods to avoid and treat chest-tube clogging. Even though
      larger tubes are thought to be associated with more pain, physicians generally
      err on the side of caution to avoid clogging and insert tubes with larger
      diameters. CONCLUSION: Results of this survey highlight the frequent problems
      with clogging with current postsurgical chest drainage systems and suggest the
      need for innovative solutions to avoid clogging complications and overcome
      clinician concern and patient pain.

PMID- 19740285
TI  - Treatment of mediastinitis with wound-vacuum without muscle flaps.
AB  - Wound vacuum may represent a new solution to the treatment of patients with
      mediastinitis. We herein present case reports of two patients with very serious
      deep wound infections of the sternum (mediastinitis) treated with wound vacuum
      without muscle flaps. The implications of this new modality of treatment are
      discussed.

PMID- 19740286
TI  - A smart method of intraoperative explantation of an aortic bioprosthesis.
AB  - Structural prosthetic valve deterioration and nonstructural dysfunction are two
      common causes of nonfatal valve events following implantation of a bioprosthetic
      valve. Using caution and skill, implantation of a bioprosthesis is relatively
      easy. On the other hand, explantation of a bioprosthesis is a challenging and
      time-consuming procedure. We have developed a surgical technique by which we were
      able to ameliorate this troublesome situation in a 79-year-old man with aortic
      stenosis in whom we had to intraoperatively explant the bioprosthesis that we
      have put in initially. Another bioprosthesis of the same kind was used to replace
      the old prosthesis with the rest of his postoperative course until dismissal
      being eventless.

PMID- 19740287
TI  - An alternative technique for tricuspid valve repair using autologous pericardium.
AB  - We developed an alternative technique to integrate the replacement of tricuspid
      septal leaflet and chordae using a fan-shaped fresh autologous pericardial patch.
      Echocardiographic evaluation showed normal mobility, and no progression of
      tricuspid regurgitation or evidence of calcification early and late after
      operation. This alternative approach appears to be an easy, rapid, and effective
      technique for tricuspid valve repair.

PMID- 19740288
TI  - Cardiac hemangioma of the left atrial appendag: a case report and discussion.
AB  - Cardiac hemangioma is an extremely rare, benign vascular tumor of the heart. In
      contrast to myxoma, hemangioma rarely involves left atrial tissue in adults and
      little information about the tumor is available. We encountered a 65-year-old
      woman with a left atrial hemangioma arising in the appendage and growing like an
      extracardiac mass. The tumor was removed from the left atrium with all the left
      appendage under cardiopulmonary bypass. Histopathological examination revealed
      that it was a cavernous-type hemangioma. Among the five described cases, this
      case was the only one in which the tumor arose from the appendage and grew into
      the pericardial cavity with resultant paroxystic atrial fibrillation.

PMID- 19740289
TI  - Primary cardiac angiosarcoma of left atrium.
AB  - Cardiac angiosarcoma usually arises from the right atrium. We report an extremely
      rare case of primary angiosarcoma originating from the left atrium in a 70-year
      old woman. This represents the ninth reported case of left-sided cardiac
      angiosarcoma in the English literature. Analysis of all nine cases shows that
      this malignant neoplasm occurs more in female patients with a mean age of 60
      years, unlike the right-sided one which typically affects male patients in their
      early 40s. The prognosis of this tumor is extremely poor with life expectancy
      lying between 3 to 34 months despite early diagnosis by imaging and multimodality
      treatment.

PMID- 19740290
TI  - Aortic embolism: an unusual clinical manifestation from a large left atrium
      aneurysm.
AB  - Aneurysms of the left atrium are rare. The most common clinical presentations are
      tachyarrhythmias and cerebral embolism. In this report, we present the case of a
      46-year-old woman presenting with an abdominal aortic embolism who required an
      aorto-femoral bypass. A medical workup revealed a left atrial aneurysm.

PMID- 19740291
TI  - Giant left ventricular aneurysm perforation: appearance in echocardiography, 64
      slice spiral computed tomography, magnetic resonance imaging, and coronary
      angiography before successful surgical treatment.

PMID- 19740292
TI  - Retrosternal pseudoaneurysm eroding the sternum in a patient six years after
      aortic valve replacement.

PMID- 19740293
TI  - Relationship between high-density lipoprotein and the progression of aortic
      valvular disease.

PMID- 19740295
TI  - Valve-sparing aortic root remodeling with reinforcement of the proximal aortic
      suture-line.
AB  - Valve-sparing aortic root remodeling is associated with the risk of bleeding from
      the proximal aortic-graft suture line and subsequent annular dilation leading to
      aortic valve failure. Herein we describe a simple technique that may be used in
      valve-sparing root operations to prevent bleeding and improve annular stability.

PMID- 19740294
TI  - Endovascular stent grafting for acute thoracic aortic pathology.
AB  - BACKGROUND: Endovascular repair of the thoracic aorta has shown reduced morbidity
      and mortality compared with open surgery. We describe our experience with
      endovascular stent grafting in the treatment of acute thoracic aortic pathology.
      METHODS: From October 2003 to January 2008, 25 patients underwent endovascular
      stent graft repair of the thoracic aorta. The underlying pathology was a
      complicated Stanford type B dissection (n = 13), a symptomatic or ruptured
      thoracic aorta aneurysm (n = 6), a symptomatic penetrating atherosclerotic ulcer
      (n = 5), or a traumatic aortic injury (n = 1). There were 21 males and four
      female patients with a mean age of 61.3 years (30-91 years). Routine surveillance
      included clinical evaluation and contrast-enhanced spiral computed tomography
      scans before discharge and at 3, 6, and 12 months after the procedure and yearly
      thereafter. RESULTS: Stent graft placement was technically successful in all
      patients. There was no intraoperative mortality. Hospital mortality was of two
      patients (8%). Paraparesis occurred in one patient (4%). Average intensive care
      unit and hospital stay was 1 and 10 days, respectively. The mean follow-up was 30
      months (range, 7-53). Late mortality was in one patient (4%), due to a type A
      dissection. During the follow-up, four patients (16%) required a second procedure
      for type I endoleak. CONCLUSIONS: Mortality and morbidity in our small series
      were low. Close follow-up is mandatory and long-term results have to be awaited.

PMID- 19740296
TI  - Spontaneous rupture of a nonaneurismatic ascending thoracic aorta.
AB  - Spontaneous rupture of the ascending thoracic aorta without any history of
      aneurysm, trauma, infection, dissection, or previous surgery is a very rare and
      potentially lethal event. We report a case of spontaneous rupture of the
      ascending aorta treated successfully. While the etiology is still unclear,
      diagnosis with bedside transesophageal echocardiography prompted emergent
      surgical intervention.

PMID- 19740297
TI  - Effect of captopril on pulmonary artery pressure following corrective surgery for
      tetralogy of fallot.
AB  - BACKGROUND: This study was designed to investigate the effect of captopril on
      systolic pulmonary arterial pressure (PAP) and circulating endothelin-1 (ET-1)
      following surgical repair of tetralogy of Fallot (TOF). METHODS AND RESULTS:
      Seventy-six consecutive patients were divided into captopril and control groups
      following successful repair of TOF. The captopril group was treated with oral
      captopril (0.2 mg/kg/day) for 12 months. Venous blood was taken before and after
      the surgery for the analysis of ET-1. Systolic PAP and ventricular function were
      assessed by Doppler echocardiography. In the control group, there was an increase
      in ET-1 and systolic PAP following the surgery (p < 0.05). In the captopril
      group, there was no significant increase in the systolic PAP and ET-1 during the
      12-month follow-up. The PAP and ET-1 values in the captopril group were lower
      than those in the control group following the surgery (p < 0.05). CONCLUSIONS:
      Systolic PAP is elevated following the complete surgical repair of TOF. Increased
      circulating ET-1 may be responsible for the elevation of PAP. Captopril treatment
      prevents postsurgical increases in systolic PAP and circulating ET-1.

PMID- 19740298
TI  - One stage surgical correction of congenital cardiac disease and congenital
      tracheal stenosis in infants and children.
AB  - OBJECTIVE: We describe our experience with patients undergoing one stage surgical
      correction of congenital cardiac disease and congenital tracheal stenosis.
      METHODS: Between February 2001 and June 2007, eight patients underwent one stage
      repair of congenital cardiac disease and congenital tracheal stenosis. Their ages
      ranged from 30 days to 3 years (mean 16.25 +/- 11.67 months) and weights from 4.2
      to 10.5 kg (mean 8.24 +/- 2.16 kg). The congenital cardiac disease was treated
      during cardiopulmonary bypass, and the tracheal stenosis was corrected
      simultaneously. RESULTS: There was no operative mortality. One 4-month-old female
      who underwent polytetrafluroethylene patch tracheoplasty developed granulation
      tissue and died 3 months postoperatively of bronchial obstruction. The medium
      term result of the remaining seven patients, after a mean follow-up of 50.4
      months (range 9 to 76 months), was a stabile and complication-free clinical
      outcome. CONCLUSION: We advocate one stage surgical correction of congenital
      cardiac disease and congenital tracheal stenosis for the treatment of these
      conditions.

PMID- 19740299
TI  - Modified "sutureless" anastomosis for primary repair of supracardiac total
      anomalous pulmonary venous connection.
AB  - Repair of total anomalous pulmonary venous connection (TAPVC) is associated with
      a risk of recurrent pulmonary venous obstruction. In this article we describe a
      technique of primary repair using a posterior approach in which a modified
      sutureless anastomosis is constructed by suturing the left atrium to the
      posterior pericardium that surrounds the pulmonary venous confluence. This
      technique avoids trauma to the pulmonary venous wall and minimizes the risk of
      distortion of the anastomosis, factors that have been implicated in the
      occurrence of subsequent pulmonary venous obstruction.

PMID- 19740300
TI  - Translocation of anomalous right coronary artery to aortic side of the
      aortopulmonary window: a different approach for a rare combination.
AB  - A case of aortopulmonary window associated with anomalous origin of the right
      coronary artery from the pulmonary artery in a four-month-old boy is reported in
      this paper with a different method of repair. In this patient, surgical repair
      was done by transferring the right coronary artery from the pulmonary artery to
      the aorta at the aortopulmonary window side. The defect at the pulmonary artery
      was repaired by a pericardial patch, so no other secondary opening was used for
      the aorta in order to reimplant the coronary artery.

PMID- 19740301
TI  - Octreotide treatment for chylothorax after congenital heart surgery.

PMID- 19740302
TI  - Long-term results of heart transplantation for end-stage valvular heart disease.
AB  - BACKGROUND: In general, heart transplantation for patients with heart failure
      improves survival. However, the outcomes of heart transplantation for patients
      with end-stage valvular heart disease are less well reported. This is a
      substantial group of patients, many of whom have had previous cardiac surgery.
      They therefore may be considered a subgroup with a poor prognosis. This study
      reports on the outcomes of heart transplantation for patients with end-stage
      valvular heart disease. PATIENTS AND METHODS: From March 1989 to December 2004,
      75 consecutive adult heart transplantations were performed for end-stage valvular
      heart disease. Clinical characteristics were retrieved from a computerized
      database. RESULTS: The early mortality risk in heart transplantation for end
      stage valvular heart disease was 13%, compared to 8% for other indications (p =
      0.12). The main causes of early death were rejection (20%) and right ventricular
      failure (20%). The total follow-up time was 415 patient-years. During the follow
      up, another 23 patients died (55/1000 patient-years of late mortality rate),
      mostly due to infection (43%) and multiorgan failure (22%). Multivariable
      analysis demonstrated that increased waiting time to heart transplantation
      correlated with increased survival (HR = 0.998, p = 0.04). The survival at 1, 5,
      10, and 15 years was 70%, 64%, 56%, and 46% compared to 78%, 68%, 53%, and 41%
      for other indications, respectively (p = 0.5). CONCLUSION: The outcomes of heart
      transplantation for patients with end-stage valvular heart disease are similar to
      those for other patients. Apparently, the longer the waiting time to heart
      transplantation the better the outcome becomes.

PMID- 19740303
TI  - Acute hemodynamic effects of cardiac resynchronization therapy in patients with
      poor left ventricular function during cardiac surgery.
AB  - BACKGROUND: Cardiac resynchronization therapy improves systolic function in
      patients with heart failure and left ventricular (LV) dyssynchrony. However, the
      effect of biventricular (BiV) pacing on perioperative hemodynamics in cardiac
      surgery is not well known. We investigated the acute hemodynamic response using
      LVdP/dt(max) in patients with depressed LV function and conduction disturbances
      undergoing cardiac surgery. METHODS: Patients with LV ejection fraction of < or
      =35%, QRS duration of >130 ms, and left bundle branch block undergoing
      aortocoronary bypass and valve surgery were included. Temporary atrial and left
      and right ventricular pacing wires were applied, and LVdP/dt(max) was measured
      with a high fidelity pressure wire in the left ventricle at the end of
      cardiopulmonary bypass. Responders had a > or =10% increase in LVdP/dt(max).
      RESULTS: Eleven patients (age 63 +/- 11 years, eight males) with a LV ejection
      fraction 0.29 +/- 0.06% were included. Compared with right ventricular pacing
      (782 +/- 153 mmHg/sec), there was a significant improvement in the mean
      LVdP/dt(max) during simultaneous BiV pacing (849 +/- 174 mmHg/sec; p = 0.034) and
      sequential BiV pacing with the LV 40 ms advanced (880 +/- 157 mmHg/sec; p =
      0.003). Improvement during LV pacing alone was not significant (811 +/- 141
      mmHg/sec). Six patients were responders with simultaneous and nine with
      sequential BiV pacing. Only sequential BiV pacing had a significant improvement
      in LV systolic pressure (p = 0.02). CONCLUSIONS: BiV pacing results in acute
      hemodynamic improvement of LV function during cardiac surgery. Optimization of
      the interventricular pacing interval contributes to the effect of the therapy.

PMID- 19740304
TI  - Deep brain hyperthermia while rewarming from hypothermic circulatory arrest.
AB  - BACKGROUND: Neurologic injury is a feared and serious long-term complication of
      cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA).
      Postoperative hyperthermia was found to enhance postischemic neurologic injury.
      The use of core temperature as the reference point through CPB assumes parallel
      changes in brain temperature. We tested the hypothesis that regional and deep
      brain temperature (DBT) differ during cooling, DHCA, and rewarming. METHODS:
      Neonatal piglets (n = 9) were subject to CPB and cooled to rectal temperature
      (RT) of 18 degrees C, 30 minutes of DHCA were initiated, and subsequently the
      piglets were rewarmed to RT of 36.5 degrees C and weaned from CPB. Temperature
      probes were inserted into the DBT targeting the caudate and thalamic nuclei,
      their position confirmed by pathology. Superficial brain temperature was measured
      by a temperature probe inserted extradurally. RT, nasopharyngeal (NPT), and
      tympanic (TT) temperatures were recorded. RESULTS: During cooling the deep brain
      cooled faster and to lower temperatures compared to RT and TT; NPT reflected DBT
      accurately. During rewarming DBT was significantly higher than RT and TT. By the
      end of rewarming the difference between the deep brain and the RT reached
      statistical significance (30 minutes: 35.1 +/- 0.7 vs. 32.3 +/- 0.7 p < 0.05,
      respectively, 40 minutes: 37.5 +/- 0.3 vs. 34.7 +/- 0.8 p < 0.05, respectively).
      CONCLUSION: Deep brain hyperthermia routinely occurs during the last stages of
      rewarming following DHCA. DBT is accurately reflected by NPT and is directly
      correlated with inflow temperature. Therefore, during rewarming inflow
      temperatures should not exceed 36 degrees C and NPT should be closely monitored.

PMID- 19740305
TI  - Retraction. Right anterior minithoracotomy for minimal access aortic valve
      replacement.

PMID- 19740306
TI  - A component of polysaccharide peptidoglycan complex on Lactobacillus induced an
      improvement of murine model of inflammatory bowel disease and colitis-associated
      cancer.
AB  - Interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3)
      signals play key roles in the pathogenesis of inflammatory bowel disease (IBD).
      We previously described that both intact cells and a cell wall-derived
      polysaccharide-peptidoglycan complex (PSPG) in a strain of lactobacillus
      [Lactobacillus casei Shirota (LcS)] inhibited IL-6 production in
      lipopolysaccharide (LPS)-stimulated lamina propria mononuclear cells (LPMCs)
      isolated from murine IBD. Diets with LcS improve murine IBD by suppression of IL
      6 synthesis in LPMCs. Moreover, LcS supplementation with fermented milk
      ameliorates disease activity in patients with active ulcerative colitis. Here, we
      focused on the specific roles of PSPG in LcS concerning their anti-inflammatory
      actions. PSPG derived from LcS, and no other strain of lactobacilli, inhibited IL
      6 production in LPS-stimulated murine IBD LPMCs. Purified PSPG-I from LcS
      inhibited IL-6 synthesis in LPS-stimulated murine IBD LPMCs through the
      inhibition of nuclear factor-kappaB. The anti-IL-6 action of LcS PSPG was
      abrogated by masking with monoclonal anti-PSPG-I. Furthermore, PSPG-I-negative L.
      casei strains (PSPG-I-negative mutant LcS: LC(DeltaPSPG-I), L. casei ATCC 334)
      did not inhibit IL-6 production. Finally, we confirmed the effects of PSPG-I on
      LcS in the models of both IBD and colitis-associated cancer (CAC). In the IBD
      model, ingestion of LcS improved ileitis and inhibited activation of IL-6/STAT3
      signaling, while ingestion of the LC(DeltaPSPG-I) strain did not. In the CAC
      model, treatment with LcS, but not the LC(DeltaPSPG-I) strain, showed tumour
      suppressive effects with an inhibition of IL-6 production in the colonic mucosa.
      These results suggested that a specific polysaccharide component in an L. casei
      strain plays a crucial role in its anti-inflammatory actions in chronic
      intestinal inflammatory disorders.

PMID- 19740307
TI  - Macrophage interleukin-6 and tumour necrosis factor-alpha are induced by
      coronavirus fixation to Toll-like receptor 2/heparan sulphate receptors but not
      carcinoembryonic cell adhesion antigen 1a.
AB  - A rapid antiviral immune response may be related to viral interaction with the
      host cell leading to activation of macrophages via pattern recognition receptors
      (PPRs) or specific viral receptors. Carcinoembryonic cell adhesion antigen 1a
      (CEACAM1a) is the specific receptor for the mouse hepatitis virus (MHV), a
      coronavirus known to induce acute viral hepatitis in mice. The objective of this
      study was to understand the mechanisms responsible for the secretion of high
      pathogenic MHV3-induced inflammatory cytokines. We report that the induction of
      the pro-inflammatory cytokines interleukin (IL)-6 and tumour necrosis factor
      (TNF)-alpha in peritoneal macrophages does not depend on CEACAM1a, as
      demonstrated in cells isolated from Ceacam1a(-/-) mice. The induction of IL-6 and
      TNF-alpha production was related rather to the fixation of the spike (S) protein
      of MHV3 on Toll-like receptor 2 (TLR2) in regions enriched in heparan sulphate
      and did not rely on viral replication, as demonstrated with denatured S protein
      and UV-inactivated virus. High levels of IL-6 and TNF-alpha were produced in
      livers from infected C57BL/6 mice but not in livers from Tlr2(-/-) mice. The
      histopathological observations were correlated with the levels of those
      inflammatory cytokines. Depending on mouse strain, the viral fixation to heparan
      sulfate/TLR2 stimulated differently the p38 mitogen-activated protein kinase
      (MAPK) and nuclear factor (NF)-kappaB in the induction of IL-6 and TNF-alpha.
      These results suggest that TLR2 and heparan sulphate receptors can act as new
      viral PPRs involved in inflammatory responses.

PMID- 19740308
TI  - Subversion of interleukin-1-mediated host defence by a nasal carrier strain of
      Staphylococcus aureus.
AB  - Staphylococcus aureus, a major source of nosocomial and community-acquired
      infections, has a nasal carriage rate exceeding 25% in the human population. To
      elucidate host-pathogen interactions pertaining to nasal carriage, we examined
      the role of interleukin-1 (IL-1) in the colonization of human nasal epithelial
      cells (NEC) by a nasal carrier strain and a non-carrier strain of S. aureus.
      Using an organotypic model of the nasal epithelium, we observed that inoculation
      with a non-carrier strain of S. aureus induced production of IL-1 from NEC, but
      the expression of this cytokine was significantly reduced when NEC were
      inoculated with a carrier strain. Moreover, both IL-1alpha and IL-1beta
      significantly decreased the growth of the nasal carrier strain of S. aureus (P <
      0.001, n = 17 to n = 25); however the growth of the non-carrier strain was
      unaffected. Interestingly, it was found that several nasal carrier strains of S.
      aureus form quorum-dependent biofilms, which can be partially inhibited when
      preincubated with IL-1alpha. Taken together these data suggest that, although
      nasal carrier strains of S. aureus are sensitive to IL-1, they display a
      significant colonization advantage by both preventing the host from expressing IL
      1 and elaborating a protective biofilm.

PMID- 19740309
TI  - Hypoxia skews dendritic cells to a T helper type 2-stimulating phenotype and
      promotes tumour cell migration by dendritic cell-derived osteopontin.
AB  - It is well recognized that tissue microenvironments are involved in regulating
      the development and function of dendritic cells (DC). Oxygen supply, which varies
      in different tissues, has been accepted as an important microenvironmental factor
      in regulating the biological functions of several immune cells and as being
      involved in tumour progression and metastasis. However, little is known about the
      effect of hypoxia on the biological functions of DC and the effect of these
      hypoxia-conditioned DC on tumour metastasis. In this study, we analysed the
      transcriptional profiles of human monocyte-derived immature DC (imDC) and mature
      DC (mDC) cultured under normoxia and hypoxia by microarray, and found a body of
      potential targets regulating the functions of DC during hypoxia. In addition, the
      phagocytic ability of hypoxic imDC markedly decreased compared with that of
      normoxic imDC. Importantly, hypoxic DC poorly induced the proliferation of
      allogeneic T cells, but polarized allogeneic CD4(+) naive T cells into a T helper
      type 2 (Th2) response. Moreover, hypoxic DC secreted large amounts of
      osteopontin, which were responsible for the enhanced migration of tumour cells.
      Therefore, our study provides new insights into the biological functions of DC
      under hypoxic conditions and one of mechanisms underlying tumour immune escape
      during hypoxia.

PMID- 19740310
TI  - Diverse T-cell differentiation potentials of human fetal thymus, fetal liver,
      cord blood and adult bone marrow CD34 cells on lentiviral Delta-like-1-modified
      mouse stromal cells.
AB  - Human haematopoietic progenitor/stem cells (HPCs) differentiate into functional T
      cells in the thymus through a series of checkpoints. A convenient in vitro system
      will greatly facilitate the understanding of T-cell development and future
      engineering of therapeutic T cells. In this report, we established a lentiviral
      vector-engineered stromal cell line (LSC) expressing the key lymphopoiesis
      regulator Notch ligand, Delta-like 1 (DL1), as feeder cells (LSC-mDL1)
      supplemented with Flt3 ligand (fms-like tyrosine kinase 3, Flt3L or FL) and
      interleukin-7 for the development of T cells from CD34(+) HPCs. We demonstrated T
      cell development from human HPCs with various origins including fetal thymus
      (FT), fetal liver (FL), cord blood (CB) and adult bone marrow (BM). The CD34(+)
      HPCs from FT, FL and adult BM expanded more than 100-fold before reaching the
      beta-selection and CD4/CD8 double-positive T-cell stage. The CB HPCs, on the
      other hand, expanded more than 1000-fold before beta-selection. Furthermore, the
      time required to reach beta-selection differed for the various HPCs, 7 days for
      FT, 14 days for FL and CB, and 35 days for adult BM. Nevertheless, all of the T
      cells developed in vitro were stalled at the double-positive or immature single
      positive stage with the exception that some CB-derived T cells arrived at a
      positive selection stage. Consequently, the LSC-mDL1 culture system illustrated
      diverse T-cell development potentials of pre- and post-natal and adult human BM
      HPCs. However, further modification of this in vitro T-cell development system is
      necessary to attain fully functional T cells.

PMID- 19740311
TI  - The hinge region fragment of immunoglobulin G improves immunogenicity of
      recombinant gonadotrophin-releasing hormone conjugated to the T-helper epitope in
      designing peptide vaccines.
AB  - In our previous study, the hinge fragment (225-232/225'-232') of human
      immunoglobulin G1 (IgG1) was used as a space peptide linker for synthesizing the
      GnRH3-hinge-MVP chimeric peptide, whereby three repeated gonadotrophin-releasing
      hormone (GnRH) units and a T-cell epitope from measles virus fusion protein (MVP)
      were amide-bond-linked at the N and C terminus, respectively, to the hinge
      peptide for producing anti-GnRH antibody responses. To investigate whether or not
      the hinge region fragment can improve the immunogenicity of GnRH, we further
      synthesized and purified GnRH3-hinge-MVP, GnRH3-hinge and GnRH3-MVP using
      recombinant DNA technology. Under high pH conditions, GnRH3-hinge-MVP was capable
      of forming double-chain structures. Immunization of male mice with the immunogens
      of GnRH3-hinge-MVP resulted in the generation of high-titre antibodies specific
      for GnRH. The synthetic GnRH3-hinge and GnRH3-MVP induced a lower titre of anti
      GnRH antibody than GnRH3-hinge-MVP. This was followed by a decrease in serum
      testosterone levels, which resulted in a low level of expression of the relaxin
      like factor gene in the testis. Our data suggest that peptide and T-cell epitopes
      oriented at the N-terminus or C-terminus of hinge peptides simplify the antigenic
      peptide conjugates and may be considered as potential synthetic immunogens.

PMID- 19740312
TI  - Elevation of interleukin-18 in chronic hepatitis C: implications for hepatitis C
      virus pathogenesis.
AB  - The outcome of hepatitis C virus (HCV) infection is determined by the interplay
      between the virus and the host immune response. Interleukin (IL)-18, an
      interferon-gamma-inducing factor, plays a critical role in the T helper type 1
      (Th1) response required for host defence against viruses, and antibodies to IL-18
      have been found to prevent liver damage in a murine model. The present study was
      conducted to investigate the possible role of IL-18 in the pathogenesis and
      persistence of HCV. IL-18 levels were measured in sera of 50 patients at various
      stages of HCV infection (resolved, chronic and cirrhosis) and compared with those
      of normal controls. IL-18 gene expression was studied in peripheral blood
      mononuclear cells (PBMC) from each group, and in liver biopsy tissue from
      patients with chronic hepatitis C. The mean levels of IL-18 in sera were markedly
      elevated in patients with chronic hepatitis and cirrhosis, and were reduced in
      patients with resolved HCV infection. The serum IL-18 concentrations were related
      to the Child-Pugh severity of liver disease in cirrhotic patients. There also
      existed a strong positive correlation of IL-18 levels with histological activity
      score and necrosis. IL-18 mRNA expression was significantly up-regulated in the
      PBMC of cirrhotic patients when compared with other groups, while in the liver,
      higher levels of IL-18 transcripts were expressed in patients with chronic
      hepatitis C. The results of our study indicate that IL-18 levels reflect the
      severity and activity of HCV infection, and may contribute to the pathogenesis
      and progression of liver disease associated with HCV.

PMID- 19740313
TI  - Selected commensal-related bacteria and Toll-like receptor 3 agonist
      combinatorial codes synergistically induce interleukin-12 production by dendritic
      cells to trigger a T helper type 1 polarizing programme.
AB  - Enteric infections remain a major health problem causing millions of deaths in
      developing countries. The interplay among the host intestinal epithelium, the
      mucosa-associated immune system and microbiota performs an essential role in gut
      homeostasis and protection against infectious diseases. Dendritic cells (DCs)
      play a key role in orchestrating protective immunity and tolerance in the gut.
      The mechanisms by which DCs adapt their responses and discriminate between
      virulent microbes and trillions of innocuous bacteria remain ill-defined. Here we
      investigated the effect of cross-talk between commensal-related bacteria (CB) and
      Toll-like receptor (TLR) agonists on DC activation and the outcome of the in
      vitro T helper response. Human monocyte-derived DCs were exposed to eight
      different Gram-positive or Gram-negative CB strains prior to activation with five
      different TLR agonists. The key polarizing cytokines interleukin (IL)-12p70, IL
      10, IL-1beta and IL-6 were quantified and the fate of naive T-cell
      differentiation was evaluated. We identified a unique combination of
      Lactobacillus casei and TLR3 signals that acted in synergy to selectively
      increase IL-12p70 secretion. Exposure to poly(I:C) converted L. casei-treated DCs
      into potent promoters of T helper type 1 (Th1) responses. We propose that DCs can
      integrate harmless and dangerous non-self signals delivered by viral products, to
      mount robust Th1 responses. Thus, in vivo DC targeting with selective probiotics
      may improve strategies for the management of enteric diseases.

PMID- 19740314
TI  - A proinflammatory cytokine interleukin-32beta promotes the production of an anti
      inflammatory cytokine interleukin-10.
AB  - A new proinflammatory cytokine interleukin-32 (IL-32) has six isoforms. Although
      IL-32 can be detected in sera from patients suffering from Crohn's disease and
      rheumatoid arthritis, it is unclear which isoforms are involved. To this end, we
      investigated the functions of the most abundant IL-32beta by generating K562-IL
      32beta stable cell lines. This report confirms, using IL-32 small interfering
      RNA, that IL-32beta induces an anti-inflammatory cytokine IL-10 in K562-IL-32beta
      cells and U937 promonocytic cells, which express endogenous IL-32beta upon
      phorbol 12-myristate 13-acetate (PMA) treatment, and monocyte-derived dendritic
      cells (DC) upon lipopolysaccharide (LPS) treatment. Interleukin-32beta was
      induced in monocyte-derived macrophages by LPS and in monocyte-derived DC by LPS,
      poly(I:C), or anti-CD40 antibody, but was not induced by PMA. We showed that IL
      32beta expression was increased in a time-dependent manner in monocyte-derived DC
      upon LPS treatment and peaked at 24 hr. Production of IL-10 was exactly
      coincident with IL-32beta expression, but IL-1beta and tumour necrosis factor
      alpha production peaked at 6 hr after LPS treatment, then steeply declined.
      Interleukin-12 p40 was induced at 9 hr and gradually increased until 48 hr, at
      which time IL-32beta and IL-10 were no longer increased. Knock-down of IL-32beta
      by IL-32 small interfering RNA led to the decrease of IL-10, but the increase of
      IL-12 in monocyte-derived DC, which means that IL-32beta promotes IL-10
      production, but limits IL-12 production. We also showed that IL-10 neutralization
      increases IL-12, IL-1beta and tumour necrosis factor-alpha production, which
      implies that IL-10 suppresses such proinflammatory cytokines. Taken together, our
      results suggest that IL-32beta upregulates the production of an anti-inflammatory
      cytokine IL-10, and then IL-10 suppresses proinflammatory cytokines.

PMID- 19740315
TI  - Balance between early life tolerance and sensitization in allergy: dependence on
      the timing and intensity of prenatal and postnatal allergen exposure of the
      mother.
AB  - Allergens can be maternally transferred to the fetus or neonate, though it is
      uncertain how this initial allergen exposure may impact the development of
      allergy responses. To evaluate the roles of timing and level of maternal allergen
      exposure in the early life sensitization of progeny, female BALB/c mice were
      given ovalbumin (OVA) orally during pregnancy, lactation or weekly at each stage
      to investigate the immunoglobulin E (IgE) antibody production and cellular
      responsiveness of their offspring. Exposure to OVA during pregnancy was also
      evaluated in OVA-specific T-cell receptor (TCR) transgenic (DO11.10) mice. The
      effect of prenatal antigen exposure on offspring sensitization was dependent on
      antigen intake, with low-dose OVA inducing tolerance followed by neonatal
      immunization that was sustained even when pups were immunized when 3 weeks old.
      These offspring received high levels of transforming growth factor-beta via
      breastfeeding. High-dose exposure during the first week of pregnancy or perinatal
      period induced transient inhibition of IgE production following neonatal
      immunization; although for later immunization IgE production was enhanced in
      these offspring. Postnatal maternal antigen exposure provided OVA transference
      via breastfeeding, which consequently induced increased offspring susceptibility
      to IgE antibody production according to week post-birth. The effect of low-dose
      maternal exposure during pregnancy was further evaluated using OVA transgenic TCR
      dams as a model. These progeny presented pronounced entry of CD4(+) T cells into
      the S phase of the cell cycle with a skewed T helper type 2 response early in
      life, revealing the occurrence of allergen priming in utero. The balance between
      tolerance and sensitization depended on the amount and timing of maternal
      allergen intake during pregnancy.

PMID- 19740316
TI  - A synergistic interferon-gamma production is induced by mouse hepatitis virus in
      interleukin-12 (IL-12)/IL-18-activated natural killer cells and modulated by
      carcinoembryonic antigen-related cell adhesion molecules (CEACAM) 1a receptor.
AB  - The production of interferon-gamma (IFN-gamma) by infiltrating natural killer
      (NK) cells in liver is involved in the control of mouse hepatitis virus (MHV)
      infection. The objectives of this study were to identify the mechanisms used by
      MHV type 3 to modulate the production of IFN-gamma by NK cells during the acute
      hepatitis in susceptible C57BL/6 mice. Ex vivo and in vitro experiments revealed
      that NK cells, expressing carcinoembryonic antigen-related cell adhesion
      molecules (CEACAM) 1a (the MHV receptor), can produce a higher level of IFN-gamma
      in the presence of both L2-MHV3 and interleukin-12 (IL-12)/IL-18. The synergistic
      production of IFN-gamma by NK cells depends on viral replication rather than
      viral fixation only, because it is inhibited or not induced in cells infected
      with ultraviolet-inactivated viruses and in cells from Ceacam1a(-/-) mice
      infected with virulent viruses. The synergistic IFN-gamma production involves the
      p38 mitogen-activated protein kinase (MAPK) rather than the extracellular signal
      regulated kinase-1/2 MAPK signalling pathway. However, the signal triggered
      through the engagement of CEACAM1a decreases the production of IFN-gamma, when
      these molecules are cross-linked using specific monoclonal antibodies. These
      results suggest that control of acute hepatitis by IFN-gamma-producing NK cells
      may depend on both production of IL-12 and IL-18 in the liver environment and
      viral infection of NK cells.

PMID- 19740317
TI  - Gene expression profiles of bone marrow cells from mice phenotype-selected for
      maximal or minimal acute inflammations: searching for genes in acute inflammation
      modifier loci.
AB  - Two mouse lines were phenotype-selected for maximum (AIRmax) or minimum (AIRmin)
      acute inflammation responses to polyacrylamide bead (Biogel) injection. These
      lines differ in terms of bone marrow granulopoiesis, neutrophil resistance to
      apoptosis, and inflammatory cytokine production during acute inflammation
      responses. We compared gene expression profiles in bone marrow cells (BMC) of
      AIRmax and AIRmin mice during acute inflammatory reactions. The BMC from femurs
      were recovered 24 hr after subcutaneous injections of Biogel. Global gene
      expression analysis was performed on CodeLink Bioarrays (36K genes) using RNA
      pools of BMC from both control and treated AIRmax and AIRmin mice. Differentially
      expressed genes were statistically established and the over-represented gene
      ontology biological process categories were identified. Upregulations of about
      136 and 198 genes were observed in the BMC of Biogel-treated AIRmax and AIRmin
      mice, respectively, but 740 genes were found to be downregulated in AIRmin mice
      compared with 94 genes in AIRmax mice. The over-represented biological themes of
      the differently expressed genes among AIRmax and AIRmin mice represent
      inflammatory response, signal transduction, cell proliferation and immune cell
      chemotaxis. We were able to demonstrate a broad downmodulation of gene
      transcripts in BMC from AIRmin mice during acute inflammation, and significant
      differentially expressed genes colocalized with previously mapped regions for
      inflammation-related phenotypes in chromosomes 1, 3, 6 and 11.

PMID- 19740318
TI  - Superantigen-presentation by rat major histocompatibility complex class II
      molecules RT1.Bl and RT1.Dl.
AB  - Rat major histocompatibility complex (MHC) class II molecules RT1.B(l) (DQ-like)
      and RT1.D(l) (DR-like) were cloned from the LEW strain using reverse
      transcription-polymerase chain reaction and expressed in mouse L929 cells. The
      transduced lines bound MHC class II-specific monoclonal antibodies in an MHC
      isotype-specific manner and presented peptide antigens and superantigens to T
      cell hybridomas. The T-cell-hybridomas responded well to all superantigens
      presented by human MHC class II, whereas the response varied considerably with
      rat MHC class II-transduced lines as presenters. The T-cell hybridomas responded
      to the pyrogenic superantigens Staphylococcus enterotoxin B (SEB), SEC1, SEC2 and
      SEC3 only at high concentrations with RT1.B(l)-transduced and RT1.D(l)-transduced
      cells as presenters. The same was true for streptococcal pyrogenic exotoxin A
      (SPEA), but this was presented only by RT1.B(l) and not by RT1.D(l). SPEC was
      recognized only if presented by human MHC class II. Presentation of Yersinia
      pseudotuberculosis superantigen (YPM) showed no MHC isotype preference, while
      Mycoplasma arthritidis superantigen (MAS or MAM) was presented by RT1.D(l) but
      not by RT1.B(l). Interestingly, and in contrast to RT1.B(l), the RT1.D(l)
      completely failed to present SEA and toxic shock syndrome toxin 1 even after
      transduction of invariant chain (CD74) or expression in other cell types such as
      the surface MHC class II-negative mouse B-cell lymphoma (M12.4.1.C3). We discuss
      the idea that a lack of SEA presentation may not be a general feature of RT1.D
      molecules but could be a consequence of RT1.D(l)beta-chain allele-specific
      substitutions (arginine 80 to lysine, asparagine 82 to aspartic acid) in the
      extremely conserved region flanking the Zn(2+)-binding histidine 81, which is
      crucial for high-affinity SEA-binding.

PMID- 19740319
TI  - A novel synthetic adjuvant enhances dendritic cell function.
AB  - The lipid core peptide (LCP) is a novel, synthetic, self-adjuvanted vaccine
      delivery system that neatly incorporates the adjuvant, carrier and antigenic
      peptides of a vaccine into a single molecular entity. This system has been
      previously shown to efficiently deliver vaccines and induce immunity. Because
      adjuvants target sentinels of the immune response, such as dendritic cells (DCs),
      that are widely distributed throughout the body to initiate specific immune
      responses, we investigated the effects of the adjuvant on DCs. Here we show that
      LCP targets vaccines to DCs and induces their activation.

PMID- 19740320
TI  - Roles of proinflammatory cytokines and the Fas/Fas ligand interaction in the
      pathogenesis of inflammatory myopathies.
AB  - Within the lesions of inflammatory myopathies, muscle fibres and invading
      mononuclear cells express Fas and Fas ligand (FasL), respectively. However, the
      roles of the Fas/FasL interaction in the pathogenesis of inflammatory myopathies
      are not fully understood. In the present study, we investigated the roles of
      proinflammatory cytokines and the Fas/FasL system in the pathogenesis of
      inflammatory myopathies. In vitro culturing of muscle cells with the
      proinflammatory cytokines interferon-gamma, tumour necrosis factor-alpha, and
      interleukin (IL)-1beta synergistically increased Fas expression, susceptibility
      to Fas-mediated apoptosis, and the expression of cytoplasmic caspases 8 and 3. In
      addition, culturing of muscle cells with activated CD4(+) T cells induced muscle
      cell apoptosis, which was partially inhibited by anti-FasL antibody. We also
      tested the possibility that T helper (Th) 17, which is an IL-17-producing helper
      T-cell subset that plays crucial roles in autoimmune and inflammatory responses,
      participates in the pathogenesis of inflammatory myopathies. Interestingly, in
      vitro culturing of dendritic cells with anti-Fas immunoglobulin M (IgM) or
      activated CD4(+) T cells induced the expression of mRNA for IL-23p19, but not for
      IL-12p35, in addition to proinflammatory cytokines. Furthermore, IL-23p19 and IL
      17 mRNAs were detected in the majority of biopsy samples from patients with
      inflammatory myopathies. Taken together, these results suggest that
      proinflammatory cytokines enhance Fas-mediated apoptosis of muscle cells, and
      that the Fas/FasL interaction between invading dendritic cells and CD4(+) T cells
      induces local production of IL-23 and proinflammatory cytokines, which can
      promote the proliferation of Th17 cells and enhance Fas-mediated apoptosis of
      muscle cells, respectively.

PMID- 19740321
TI  - Toll-like receptor agonists induce inflammation and cell death in a model of head
      and neck squamous cell carcinomas.
AB  - Toll-like receptors (TLRs) are increasingly implicated in the pathogenesis of
      cancer. The present study describes TLR expression and function in healthy and
      malignant airway epithelial cells. The squamous cell carcinoma cell line Detroit
      562 was compared with the healthy bronchial epithelial cell line NL-20 and
      primary human nasal epithelial cells (HNECs). TLR2, TLR3 and TLR5 were present in
      primary head and neck squamous cell carcinomas (HNSCCs). Consistent with this,
      Detroit-562 expressed TLR2, TLR3 and TLR5, whereas NL-20 expressed mainly TLR3
      and HNECs expressed TLR2-5. In Detroit-562, Pam(3)CSK(4), poly(I:C) and
      flagellin, ligands for TLR2, TLR3 and TLR5, respectively, induced an up
      regulation of intercellular adhesion molecule 1 (ICAM-1), an increase in
      interleukin (IL)-6 and IL-8 secretion and a decrease in cell viability.
      Additionally, poly(I:C) affected IL-1beta production and the migratory behaviour
      of Detroit-562. NL-20 responded with a slight increase in IL-8 secretion upon
      poly(I:C) stimulation. Poly(I:C) induced a small increase in IL-1beta, IL-6 and
      IL-8 production in HNECs, while Pam(3)CSK(4) increased viability. The TLR
      signalling was transcription-dependent, but the pathways involved differed among
      TLRs as well as cells. In Detroit-562, TLR2 and TLR5 activation was mediated via
      c-jun N-terminal kinase (JNK)-, p38-, phosphatidylinositol 3-kinase (PI3K)- and
      nuclear factor (NF)-kappaB-related pathways, while TLR3 was dependent on NF
      kappaB. In NL-20, TLR3 signalled via p38, and in HNECs, NF-kappaB, JNK and
      extracellular signal-regulated kinase (ERK) appeared to be involved. We found
      that TLR agonists induced a robust response in HNSCCs, characterized by
      generation of inflammation and cell death. A similar response was not seen in
      normal epithelial cells. Thus, the TLR system should be considered an important
      target in future antitumour immunotherapy.

PMID- 19740322
TI  - Co-immunization with an optimized plasmid-encoded immune stimulatory interleukin,
      high-mobility group box 1 protein, results in enhanced interferon-gamma secretion
      by antigen-specific CD8 T cells.
AB  - DNA vaccination is a novel immunization strategy that has great potential for the
      development of vaccines and immune therapeutics. This strategy has been highly
      effective in mice, but is less immunogenic in non-human primates and in humans.
      Enhancing DNA vaccine potency remains a challenge. It is likely that antigen
      presenting cells (APCs), and especially dendritic cells (DCs), play a significant
      role in the presentation of the vaccine antigen to the immune system. A new study
      reports the synergistic recruitment, expansion and activation of DCs in vivo by
      high-mobility group box 1 (HMGB1) protein. Such combinational strategies for
      delivering vaccine in a single, simple platform will hypothetically bolster the
      cellular immunity in vivo. Here, we combined plasmid encoding human
      immunodeficiency virus-1 (HIV-1) Gag and Env with an HMGB1 plasmid as a DNA
      adjuvant in BALB/c mice (by intramuscular immunization via electroporation), and
      humoral and cellular responses were measured. Co-administration of this potent
      immunostimulatory adjuvant strongly enhanced the cellular interferon-gamma (IFN
      gamma) and humoral immune response compared with that obtained in mice immunized
      with vaccine only. Our results show that co-immunization with HMGB1 can have a
      strong adjuvant activity, driving strong cellular and humoral immunity that may
      be an effective immunological adjuvant in DNA vaccination against HIV-1.

PMID- 19740323
TI  - Effect of sialic acid loss on dendritic cell maturation.
AB  - Sialic acids are key structural determinants and contribute to the functionality
      of a number of immune cell receptors. Previously, we demonstrated that
      differentiation of human dendritic cells (DCs) is accompanied by an increased
      expression of sialylated cell surface structures, putatively through the activity
      of the ST3Gal.I and ST6Gal.I sialyltransferases. Furthermore, DC endocytosis was
      reduced upon removal of the cell surface sialic acid residues by neuraminidase.
      In the present work, we evaluate the contribution of the sialic acid
      modifications in DC maturation. We demonstrate that neuraminidase-treated human
      DCs have increased expression of major histocompatibility complex (MHC) and
      costimulatory molecules, increased gene expression of specific cytokines and
      induce a higher proliferative response of T lymphocytes. Together, the data
      suggest that clearance of cell surface sialic acids contributes to the
      development of a T helper type 1 proinflammatory response. This postulate is
      supported by mouse models, where elevated MHC class II and increased maturation
      of specific DC subsets were observed in DCs harvested from ST3Gal.I(-/-) and
      ST6Gal.I(-/-) mice. Moreover, important qualitative differences, particularly in
      the extent of reduced endocytosis and in the peripheral distribution of DC
      subsets, existed between the ST3Gal.I(-/-) and ST6Gal.I(-/-) strains. Together,
      the data strongly suggest not only a role of cell surface sialic acid
      modifications in maturation and functionality of DCs, but also that the sialic
      acid linkages created by different sialyltransferases are functionally distinct.
      Consequently, with particular relevance to DC-based therapies, cell surface
      sialylation, mediated by individual sialyltransferases, can influence the
      immunogenicity of DCs upon antigen loading.

PMID- 19740324
TI  - Granulocyte colony-stimulating factor-induced immature myeloid cells inhibit
      acute graft-versus-host disease lethality through an indoleamine dioxygenase
      independent mechanism.
AB  - Granulocyte colony-stimulating factor (G-CSF)-mobilized donor graft tissue used
      for peripheral blood stem cell transplantation contains a large number of
      immature myeloid cells that suppress alloreactive donor T cells, resulting in an
      inhibition of acute graft-versus-host disease (GVHD). However, the molecular
      mechanism underlying the suppressive function of immature myeloid cells is not
      fully understood. Here, we investigated whether indoleamine 2,3-dioxygenase (IDO)
      is related to the suppressive mechanism of G-CSF-induced immature myeloid cells
      (gMCs). We found that Gr-1(+) CD11b(+) cells were highly induced in G-CSF
      injected donor graft tissue, which is a phenotype of immature myeloid cells,
      resulting in an inhibition of acute GVHD lethality by suppressing alloreactive
      donor T-cell expansion. IDO was not detected in primary isolated gMCs; however,
      this enzyme was markedly induced after treatment with interferon-gamma (IFN
      gamma). This level was significantly higher in IFN-gamma-treated gMCs than in
      bone marrow myeloid cells, which promote alloreactive T-cell responses. We next
      investigated the functional role of IDO in gMC-mediated inhibition of acute GVHD
      lethality. We found no changes in gMC-mediated survival or alloreactive donor T
      cell suppression when IDO activity was blocked using 1-methyl tryptophan. In
      addition, there was no difference in gMC-mediated survival rates between
      recipients transferred with either wild-type gMCs or IDO(-/-) gMCs. Taken
      together, our data suggest that gMC-mediated inhibition of lethal acute GVHD is
      through an IDO-independent mechanism.

PMID- 19740325
TI  - The immunogenicity of L1210 lymphoma clones correlates with their ability to
      function as antigen-presenting cells.
AB  - Major histocompatibility complex class II (MHCII) antigen expression is directly
      correlated with immunogenicity, and inversely correlated with tumorigenicity, in
      clones of the L1210 murine B lymphoma. Moreover, loss of MHCII expression on
      human diffuse large B-cell lymphoma is associated with dramatic decreases in
      patient survival. Thus, the role that MHCII antigens play in the progression of B
      cell lymphomas is clinically important. In this study, we investigated the basis
      for the immunogenicity of MHCII(+) L1210 clones. Immunogenic, but not tumorigenic
      L1210 clones stimulated the proliferation of naive T cells and their interleukin
      (IL)-2 production, which indicates that the immunogenic clones can function as
      antigen-presenting cells (APCs). However, subclonal variants of the immunogenic
      L1210 clones, which form tumours slowly in mice, could not activate T cells. The
      costimulatory molecules B7-1, B7-2 and CD40 were expressed on the immunogenic
      L1210 clones, but not the tumorigenic clones. Importantly, the tumour-forming
      subclonal variants expressed MHCII and B7-1, but lacked B7-2 and CD40. These
      results suggest that MHCII and B7-1 expression on L1210 cells is insufficient to
      activate naive T cells, and, furthermore, loss of B7-2 and/or CD40 expression
      contributes to the decreased immunogenicity of L1210 subclones. Blocking B7-1 or
      B7-2 function on immunogenic L1210 cells reduced their capacity to activate naive
      T cells. Furthermore, incubation of immunogenic L1210 cells with CD40 antibodies
      significantly enhanced APC function. Therefore, the immunogenicity of L1210 cells
      directly correlates (i) with their ability to stimulate naive T cells, and (ii)
      with the concomitant expression of MHCII, B7-1, B7-2, and CD40.

PMID- 19740326
TI  - Roles of phosphatidylinositol 3-kinase and p38 mitogen-activated protein kinase
      in the regulation of protein kinase C-alpha activation in interferon-gamma
      stimulated macrophages.
AB  - Members of the protein kinase C (PKC) family are activated by interferon-gamma
      (IFN-gamma) and modulate IFN-gamma-induced cellular responses by regulating the
      activity of transcription factors. We previously reported that PKC-alpha enhances
      the ability of IFN regulatory factor-1 to transactivate the class II
      transactivator (CIITA) promoter IV in IFN-gamma-stimulated macrophages. In
      addition, we showed that IFN-gamma induces the nuclear translocation of PKC-alpha
      but the mechanisms for this remain to be elucidated. In this study, we sought to
      identify signalling pathways involved in IFN-gamma-induced activation of PKC
      alpha and to characterize their potential roles in modulating IFN-gamma-induced
      responses in macrophages. IFN-gamma-mediated nuclear translocation of PKC-alpha
      was a Janus activated kinase 2 (JAK2)-independent process, which required
      phosphatidylinositol 3-kinase (PI3K) and p38 mitogen-activated protein kinase
      (MAPK). However, PKC-alpha phosphorylation was independent of PI3K and p38 MAPK,
      indicating that IFN-gamma-induced phosphorylation and nuclear translocation of
      PKC-alpha are mediated by distinct mechanisms. In addition, inhibition of PI3K,
      but not of p38 MAPK, strongly impaired IFN-gamma-induced CIITA and MHC II gene
      expression. Finally, PKC-alpha associated with signal transducer and activator of
      transcription 1 (STAT1) and was required for the phosphorylation of STAT1 on
      serine 727 in IFN-gamma-stimulated macrophages. Taken together, our data indicate
      that PI3K and p38 MAPK modulate IFN-gamma-stimulated PKC-alpha nuclear
      translocation independently of JAK2 activity and that both PI3K and PKC-alpha are
      required for type IV CIITA and MHC II gene expression in IFN-gamma-stimulated
      macrophages.

PMID- 19740327
TI  - Spontaneous complement activation on human B cells results in localized membrane
      depolarization and the clustering of complement receptor type 2 and C3 fragments.
AB  - While our previous studies have demonstrated that complement activation induced
      by complement receptors type 2 (CR2/CD21) and 1 (CR1/CD35) results in C3-fragment
      deposition and membrane attack complex (MAC) formation in human B cells, the
      consequences of these events for B-cell functions remain unknown. In the present
      study, we show that CR2-induced complement activation results in membrane
      depolarization, as indicated by annexin V binding, with kinetics similar to those
      of C3-fragment deposition and different from those of MAC formation. On the other
      hand, like MAC formation, depolarization requires activation of complement via
      the alternative pathway, as indicated by total inhibition upon neutralization of
      factor D, and is abrogated by combined blockade of CR1 and CR2, but not of either
      receptor alone. The membrane depolarization is not associated with the apoptosis
      of B cells, as examined by co-staining with APO-2.7 or by the TdT-mediated biotin
      dUTP nick-end labelling (TUNEL) assay. Confocal microscopy revealed that
      depolarization and C3 deposition, unlike MAC deposition, are limited to
      restricted areas on the B-cell surface. Double staining revealed a close
      association between the C3-fragment patches and membrane depolarization, as well
      as redistribution of lipid rafts to these areas. We propose that these events may
      play a role in the regulation of B-cell signalling and cross-talk with T cells.

PMID- 19740328
TI  - Distinct regulatory roles of transforming growth factor-beta and interleukin-4 in
      the development and maintenance of natural and induced CD4+ CD25+ Foxp3+
      regulatory T cells.
AB  - The development and function of CD4(+) CD25(+) Foxp3(+) regulatory T cells
      (Tregs) are strictly regulated by cytokines. Here we show that transforming
      growth factor-beta (TGF-beta) and interleukin-4 (IL-4) play a crucial and
      antagonistic role in the development of Tregs. Additionally, these cytokines also
      have distinct effects on the maintenance of natural (nTregs) and antigen-induced
      (iTregs) Tregs. Using double-staining and tracking of proliferation of purified
      and carboxyflourescein succinimidyl ester (CFSE)-labelled mouse T-cell
      subpopulations we demonstrated that CD4(+) CD25(+) Foxp3(+) iTregs develop upon
      alloantigenic stimulation in the presence of TGF-beta exclusively from CD4(+)
      CD25(-) Foxp3(-) precursors. Both the induction of Foxp3 expression and Treg
      proliferation were prevented when the cells were stimulated in the presence of IL
      4. By contrast, nTregs did not proliferate in the presence of the antigen and TGF
      beta, and partially lost their Foxp3 expression. IL-4 not only prevented the
      development of iTregs, but also down-regulated the level of Foxp3 mRNA and
      decreased the number of Foxp3(+) cells in a population of iTregs. Further
      analyses proved that IL-4 decreased the expression of Foxp3 only in a population
      of iTregs, whereas it substantially supported the survival of nTregs. Functional
      experiments showed that Tregs induced in the presence of alloantigen and TGF-beta
      inhibited, on a per-cell basis, cell proliferation comparably to nTregs, and
      their suppressive capacity was not modulated by IL-4. These data suggest that TGF
      beta and IL-4 differentially regulate the development of Tregs and distinctly
      sustain Foxp3 expression and the number of nTregs and iTregs, but have no
      influence on the suppressive activity of Tregs on a per-cell basis.

PMID- 19740329
TI  - Interleukin-12 is sufficient to promote antigen-independent interferon-gamma
      production by CD8 T cells in old mice.
AB  - Numerous functional defects have been identified in naive T cells from aged mice,
      including deficiencies in proliferation, cytokine production and signal
      transduction. It is well documented that the ratio of naive to memory T cells
      significantly decreases with age resulting in the majority of T cells from aged
      hosts expressing activated/memory T-cell markers (CD44(hi)), yet it is unclear
      whether T cells with a CD44(hi) phenotype in aged hosts are functionally
      equivalent to T cells with a similar phenotype in young hosts. We have identified
      a population of CD44(hi) CD8 T cells in old mice that are capable of secreting
      interferon-gamma (IFN-gamma) in response to interleukin-12 (IL-12) stimulation.
      This occurred in the absence of T-cell receptor engagement, a function that was
      not observed in CD8 T cells from young mice. This phenotype was associated with
      increased IL-12 receptor beta2 gene expression and IL-12 induced signal
      transducer and activator of transcription 4 (STAT-4) activation, even when CD8 T
      cell numbers from young and old mice were normalized for CD44(hi) expression.
      Furthermore, we demonstrate that IL-12-induced STAT-4 activation was required for
      T helper type 1 (Th1) cytokine-induced IFN-gamma production in CD8 T cells. These
      data illustrate that old mice possess a specialized subset of CD44(hi) CD8 T
      cells with an enhanced responsiveness to IL-12, enabling these cells to produce
      substantial amounts of IFN-gamma in response to Th1 cytokine stimulation. We have
      therefore identified a functional difference in the populations of CD44(hi) CD8 T
      cells from young and old mice, and believe that understanding age-associated
      immunological changes is essential for helping the elderly combat deadly
      diseases.

PMID- 19740330
TI  - Apoptosis of macrophages during pulmonary Mycobacterium bovis infection:
      correlation with intracellular bacillary load and cytokine levels.
AB  - Apoptosis of macrophages infected with pathogenic mycobacteria is an alternative
      host defence capable of removing the environment supporting bacterial growth. In
      this work the influence of virulence and bacterial load on apoptosis of alveolar
      macrophages during the initial phase of infection by Mycobacterium bovis was
      investigated. BALB/c mice were infected intratracheally with high or low doses of
      the virulent (ATCC19274) or attenuated (bacillus Calmette-Guerin Moreau) strains
      of M. bovis. The frequency of macrophage apoptosis, the growth of mycobacteria in
      macrophages, and the in situ levels of the cytokines tumour necrosis factor-alpha
      (TNF-alpha), interleukin-10 (IL-10) and IL-12 and of the anti-apoptotic protein
      Bcl-2 were measured at day 3 and day 7 post-infection. An increase of macrophage
      apoptosis was observed after infection with both strains but the virulent strain
      induced less apoptosis than the attenuated strain. On the 3rd day after infection
      with the virulent strain macrophage apoptosis was reduced in the high-dose group,
      while on the 7th day post-infection macrophage apoptosis was reduced in the low
      dose group. Inhibition of apoptosis was correlated with increased production of
      IL-10, reduced production of TNF-alpha and increased production of Bcl-2. In
      addition, the production of IL-12 was reduced at points where the lowest levels
      of macrophage apoptosis were observed. Our results indicate that virulent
      mycobacteria are able to modulate macrophage apoptosis to an extent dependent on
      the intracellular bacterial burden, which benefits its intracellular growth and
      dissemination to adjacent cells.

PMID- 19740331
TI  - Astrocyte elevated gene-1 (AEG-1) is induced by lipopolysaccharide as toll-like
      receptor 4 (TLR4) ligand and regulates TLR4 signalling.
AB  - Astrocyte elevated gene-1 (AEG-1) is induced by human immunodeficiency virus 1
      (HIV-1) infection and involved in tumour progression, migration and invasion as a
      nuclear factor-kappaB (NF-kappaB) -dependent gene. The involvement of AEG-1 on
      lipopolysaccharide (LPS) -induced proinflammatory cytokine production was
      examined. AEG-1 was induced via NF-kappaB activation in LPS-stimulated U937 human
      promonocytic cells. AEG-1 induced by LPS subsequently regulated NF-kappaB
      activation. The prevention of AEG-1 expression inhibited LPS-induced tumour
      necrosis factor-alpha and prostaglandin E(2) production. The AEG-1 activation was
      not induced by toll-like receptor ligands other than LPS. Therefore, AEG-1 was
      suggested to be a LPS-responsive gene and involved in LPS-induced inflammatory
      response.

PMID- 19740332
TI  - Suppression of antitumour protective cytotoxic T lymphocyte responses to a human
      papillomavirus 16 E7 DNA vaccine by coinjection of interleukin-12 complementary
      DNA: involvement of nitric oxide in immune suppression.
AB  - Interleukin-12 (IL-12) has been shown to enhance cellular immunity in vitro and
      in vivo. The beneficial roles of IL-12 as a DNA vaccine adjuvant have been
      commonly observed. Here the impact of IL-12 complementary DNA (cDNA) as an
      adjuvant for a human papillomavirus (HPV) type 16 E7 DNA vaccine is investigated
      in a mouse tumour model. Coinjection of E7 DNA vaccine with IL-12 cDNA completely
      suppressed antigen-specific cytotoxic T-lymphocyte (CTL) responses, leading to a
      complete loss of antitumour protection from a tumour cell challenge. In addition,
      antigen-specific antibody and T helper cell proliferative responses were also
      suppressed by IL-12 cDNA coinjection. This inhibition was observed over different
      IL-12 cDNA doses. Furthermore, separate leg injections of IL-12 and E7 cDNAs
      suppressed antigen-specific CTL and tumour protective responses, but not antibody
      and T helper cell proliferative responses, suggesting different pathways for
      suppression of these two separate responses. Further knockout animal studies
      demonstrated that interferon-gamma and nitric oxide are not directly associated
      with suppression of antigen-specific antibody responses by IL-12 cDNA
      coinjection. However, nitric oxide was found to be involved in suppression of
      antigen-specific CTL and tumour protective responses by IL-12 cDNA coinjection.
      These data suggest that coinjection of IL-12 cDNA results in suppression of E7
      specific CTL responses through nitric oxide, leading to a loss of antitumour
      resistance in this DNA vaccine model. This study further shows that the adjuvant
      effect of IL-12 is dependent on the antigen types tested.

PMID- 19740333
TI  - Dynamics of the CD8 T-cell response following yellow fever virus 17D
      immunization.
AB  - Management of yellow fever is focused on the prevention of illness by the use of
      the yellow fever virus (YFV) 17D vaccine. The role of neutralizing antibodies in
      protection is generally accepted with YFV-specific T cells likely contributing to
      the control of viral replication. We studied CD8(+) T-cell responses to four
      defined human leucocyte antigen-B35-restricted epitopes in YFV vaccine recipients
      as a model of the kinetics of cytotoxic T-lymphocyte responses to an acute human
      viral infection. Multiple features of these epitope-specific responses were
      analysed after vaccination including magnitude, cytokine production, phenotype
      and T-cell receptor repertoire. Peak peptide-specific interferon-gamma (IFN
      gamma) responses of almost 1% of CD8(+) T cells were seen as early as 2 weeks
      post-vaccination; however, dominant responses varied between donors. Peptide
      specific responses were still detectable at 54 months post-vaccination. Tetramer
      positive cells, at high frequencies, were detected as early as 7-9 days, before
      detectable IFN-gamma-producing cells, suggesting a defect in the functional
      capacity of some antigen-specific cells early post-vaccination. The predominant
      memory phenotype of the tetramer-positive population was a differentiated
      effector (CD45RA(+) CCR7(-) CD62L(-)) phenotype. The T-cell receptor Vbeta
      analysis revealed a diverse oligoclonal repertoire in tetramer-positive T-cell
      populations in two individuals. These characteristics of the YFV-specific T-cell
      response could contribute to vaccine effectiveness.

PMID- 19740334
TI  - Adenosine regulates CD8 T-cell priming by inhibition of membrane-proximal T-cell
      receptor signalling.
AB  - Adenosine is a well-described anti-inflammatory modulator of immune responses
      within peripheral tissues. Extracellular adenosine accumulates in inflamed and
      damaged tissues and inhibits the effector functions of various immune cell
      populations, including CD8 T cells. However, it remains unclear whether
      extracellular adenosine also regulates the initial activation of naive CD8 T
      cells by professional and semi-professional antigen-presenting cells, which
      determines their differentiation into effector or tolerant CD8 T cells,
      respectively. We show that adenosine inhibited the initial activation of murine
      naive CD8 T cells after alphaCD3/CD28-mediated stimulation. Adenosine caused
      inhibition of activation, cytokine production, metabolic activity, proliferation
      and ultimately effector differentiation of naive CD8 T cells. Remarkably,
      adenosine interfered efficiently with CD8 T-cell priming by professional antigen
      presenting cells (dendritic cells) and semi-professional antigen-presenting cells
      (liver sinusoidal endothelial cells). Further analysis of the underlying
      mechanisms demonstrated that adenosine prevented rapid tyrosine phosphorylation
      of the key kinase ZAP-70 as well as Akt and ERK1/2 in naive alphaCD3/CD28
      stimulated CD8 cells. Consequently, alphaCD3/CD28-induced calcium-influx into CD8
      cells was reduced by exposure to adenosine. Our results support the notion that
      extracellular adenosine controls membrane-proximal T-cell receptor signalling and
      thereby also differentiation of naive CD8 T cells. These data raise the
      possibility that extracellular adenosine has a physiological role in the
      regulation of CD8 T-cell priming and differentiation in peripheral organs.

PMID- 19740335
TI  - Peripheral blood T4 cell surface CCR5 density as a marker of activity in
      rheumatoid arthritis treated with anti-CD20 monoclonal antibody.
AB  - The chemokine (C-C motif) receptor CCR5 and its ligand CCL5 play key roles in the
      intra-articular recruitment of peripheral blood mononuclear cells (PBMC) in
      rheumatoid arthritis (RA). Therefore, using quantitative cytofluorometry, we
      followed T4 cell surface CCR5 density in 27 subjects with RA before and after
      treatment with the anti-CD20 monoclonal antibody rituximab. We observed low T4
      cell surface CCR5 densities before treatment, which correlated positively with
      disease activity, as determined using a disease activity score evaluated on 28
      joints (DAS 28), and negatively with CCL5 mRNA concentrations in PBMC,
      contrasting with a high proportion of intracellular CCR5 molecules, a pattern
      compatible with ligand-induced CCR5 internalization. At 3 months post-treatment,
      CCL5 mRNA expression in PBMC declined, whereas T4 cell surface CCR5 densities
      increased proportionally to the decrease in DAS 28. Thus, peripheral blood T4
      cell surface CCR5 density is a good surrogate marker of RA activity and of the
      efficiency of anti-CD20 therapy.

PMID- 19740336
TI  - Impact of human immunodeficiency virus 1 infection and inflammation on the
      composition and yield of cervical mononuclear cells in the female genital tract.
AB  - Cervical cytobrush sampling is a relatively non-invasive method for obtaining
      mucosal cells from the female genital tract. To define mucosal immune cells
      sampled by cervical cytobrushing and to validate this approach for local immunity
      studies, we investigated the impact of human immunodeficiency virus (HIV) status
      and inflammation on the yield and composition of cervical cytobrush specimens.
      Cervical cytobrush samples were obtained from 89 chronically HIV-infected and 46
      HIV-negative women. The HIV-infected women had significantly higher yields of
      CD3(+), CD45(+), CD19(+), CD14(+), Langerin(+) and CD24(+) cells than the
      uninfected women. While cytobrush-derived T cells from uninfected women were
      predominantly CD4(+) (4.2 CD4 : 1 CD8), CD8(+) T cells were predominant in HIV
      infected women (0.6 CD4 : 1 CD8). The majority of CD4(+) and CD8(+) T cells from
      HIV-infected and uninfected women were of the effector memory (CD45RA(-) CCR7(-)
      CD27(-)) phenotype. HIV-infected women had significantly elevated levels of
      interleukin (IL)-1beta, IL-6 and IL-8 in cervical supernatants compared with
      uninfected women. We observed a significant positive correlation between T-cell
      counts and IL-1beta, tumour necrosis factor (TNF)-alpha and IL-12 concentrations.
      Neutrophil counts correlated significantly with cervical concentrations of IL
      1beta, TNF-alpha, IL-8, IL-6 and IL-10. Antigen-presenting cell numbers
      correlated significantly with TNF-alpha and IL-12 concentrations. HIV-infected
      women on antiretroviral therapy had similar levels of cervical lymphocyte
      infiltration and inflammation to women naive to therapy. In conclusion, we
      suggest that inflammation at the cervix and HIV infection are likely to be key
      determinants in the absolute number of mucosal immune cells recovered by cervical
      cytobrushing.

PMID- 19740337
TI  - Bone morphogenetic protein-6 induces the expression of inducible nitric oxide
      synthase in macrophages.
AB  - Bone morphogenetic proteins (BMPs) are members of the transforming growth factor
      beta (TGF-beta) superfamily. In the present study, we investigated the effect of
      BMPs on the production of inducible nitric oxide synthase (iNOS) in the murine
      macrophage cell line, RAW 264.7, and in mouse peritoneal macrophages. Among the
      BMPs, only BMP-6 induced iNOS expression in a time-dependent and dose-dependent
      manner in both cell types. Induction of iNOS was inhibited by both cycloheximide
      and actinomycin D, indicating that the induction of iNOS expression by BMP-6
      requires new protein synthesis. Mechanistic studies revealed that the BMP-6
      induced iNOS expression requires both Smads and nuclear factor-kappa B (NF
      kappaB) signalling pathways. Furthermore, induction of interleukin-1beta (IL
      1beta) was necessary for iNOS induction by BMP-6. These observations suggest that
      BMP-6 stimulates macrophages to produce iNOS through IL-1beta via Smad and NF
      kappaB signalling pathways and that BMP-6 may be an important regulator of
      macrophages.

PMID- 19740338
TI  - Osteopontin is not crucial to protective immunity during murine tuberculosis.
AB  - Upon infection with Mycobacterium (M.) tuberculosis, the development of a strong
      T helper 1 (Th1)-mediated adaptive immune response is considered as being most
      important for containment of the infection. Osteopontin (OPN) is a phosphorylated
      glycoprotein that is chemotactic for inflammatory cells and has been implicated
      in the induction of Th1 responses and granulomatous disease. We tested the
      hypothesis that OPN facilitates protective immunity during M. tuberculosis
      infection using wild-type (WT) and OPN knockout (KO) mice in a model of pulmonary
      tuberculosis. OPN expression was up-regulated in alveolar macrophages and
      lymphoid cells during M. tuberculosis infection. There were no significant
      differences in bacterial outgrowth, inflammation or recruitment of lymphocytes,
      macrophages and polymorphonuclear cells in the lungs after 2 and 5 weeks of
      infection. However, the numbers of CD4(+) and CD8(+) T cells were reduced in the
      absence of OPN 5 weeks after infection. Similar concentrations of cytokine were
      observed in lungs from both WT mice and OPN KO mice; however, there was a trend
      towards decreased levels of interferon-gamma (IFN-gamma) in OPN KO mice 5 weeks
      after infection. Despite an unaltered immune response in the early phase of
      tuberculosis, OPN KO mice had a modest survival advantage. Of note, both
      pulmonary bacterial loads and lung inflammation were reduced in these mice 31
      weeks after infection. These data suggest that OPN is not crucial for protective
      immunity upon M. tuberculosis infection and during the late phase of tuberculosis
      may even be detrimental for the host.

PMID- 19740339
TI  - IFN-gamma production in response to Tax 161-233, and frequency of CD4+ Foxp3+ and
      Lin HLA-DRhigh CD123+ cells, discriminate HAM/TSP patients from asymptomatic HTLV
      1-carriers in a Peruvian population.
AB  - Human T-lymphotropic virus 1 (HTLV-1) can cause HTLV-1-associated
      myelopathy/tropical spastic paraparesis (HAM/TSP). The objective of this study
      was to gain insight into the pathogenesis of HAM/TSP by focusing on the CD8(+) T
      cell response. Twenty-three HTLV-1-seronegative controls (SC), 29 asymptomatic
      HTLV-1 carriers (AC) and 48 patients with HAM/TSP were enrolled in the study. We
      evaluated the production of interferon-gamma (IFN-gamma) in peripheral blood
      mononuclear cells stimulated with Tax overlapping peptides, the expression of
      genes related to the CD8(+) cytotoxic T-cell response, the frequency of CD4(+)
      Foxp3(+) cells and of dendritic cells, and the HTLV-1 provirus load (PVL). The
      frequency of cells producing IFN-gamma in response to Tax 161-233, but not to Tax
      11-19, discriminated patients with HAM/TSP from AC. The increased pro
      inflammatory response observed in patients with HAM/TSP was shared by AC with a
      high PVL, who also exhibited lower levels of granzyme H mRNA in unstimulated
      CD8(+) T cells than AC with a low PVL. Patients with HAM/TSP showed higher
      frequencies of CD4(+) Foxp3(+) cells and lower frequencies of plasmacytoid
      dendritic cells (pDC) than AC. Our findings are consistent with a model in which
      HTLV-1, along with the host genetic background, drives quantitative and
      qualitative changes in pDC and CD4(+) Foxp3(+) cells that lead to a predominance
      of inflammatory responses over lytic responses in the CD8(+) T-cell response of
      individuals predisposed to develop HAM/TSP.

PMID- 19740340
TI  - The CTLA-4 gene polymorphisms are associated with CTLA-4 protein expression
      levels in multiple sclerosis patients and with susceptibility to disease.
AB  - Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is an important molecule in the down
      regulation of T-cell activation. A study was undertaken to evaluate the
      association of the CTLA-4 gene polymorphisms -319C/T, +49A/G, (AT)(n), CT60A/G
      and Jo31G/T with the levels of membrane CTLA-4 (mCTLA-4) and cytoplasmic CTLA-4
      (cCTLA-4) in CD4(+) T lymphocytes from patients with multiple sclerosis (MS) and
      with susceptibility to MS, and the course of the disease. It was found that the
      Jo31GG and CT60GG genotypes were associated with decreased mean fluorescence
      intensity (MFI) of total CTLA-4 (mCTLA-4 + cCTLA-4) molecules in CD4(+) T cells
      from both relapsing-remitting (RR) and secondary progressive (SP) MS patients
      compared with others. Consequently, possessing the Jo31G allele and/or the CT60G
      allele were associated with susceptibility to MS. The percentages of cells
      expressing mCTLA-4 and cCTLA-4 in RR patients were higher in carriers of the
      alleles non-predisposing to MS (namely CT60A and Jo31T), but the percentages of
      corresponding cells were unexpectedly significantly lower in SP patients than in
      RR patients. Increased risk of paresthesia and pyramidal signs as a first
      manifestation of disease, and earlier transition to the SP form in those
      patients, was also noted. It is hypothesized that the decreasing frequencies of
      cells expressing immunosuppressive mCTLA-4 and cCTLA-4 in carriers of alleles non
      predisposing to MS (i.e. CT60A and Jo31T) may lead to inadequate down-regulation
      of ongoing T-cell responses in these patients and, as a consequence, earlier
      progression of disease from the RR form to the SP form.

PMID- 19740341
TI  - Local irradiation of murine melanoma affects the development of tumour-specific
      immunity.
AB  - Radiation therapy affects the immune system. In addition to killing
      radiosensitive immune cells, it can induce functional changes in those cells that
      survive. Our recent studies showed that the exposure of dendritic cells (DCs) to
      radiation in vitro influences their ability to present tumour antigen in vivo.
      Here we show that local radiation therapy of B16 melanoma tumours inhibits the
      development of systemic immunity to the melanoma antigen MART-1. This inhibition
      could not be overcome by intratumoral injection of DCs expressing human MART-1
      after radiation therapy, suggesting that a form of immune suppression might have
      developed. On the other hand, injection of MART-expressing DCs prior to tumour
      irradiation was able to prevent inhibition from developing. These results suggest
      that local radiation therapy may block the generation of immunity under some
      circumstances and that strategies may be required to prevent this and allow
      radiation-induced cell death to translate fully into the development of systemic
      immunity.

PMID- 19740342
TI  - Bacterial signalling overrides cytokine signalling and modifies dendritic cell
      differentiation.
AB  - Heterogeneity of dendritic cells (DC) is evident in the gut-associated lymphoid
      tissue and determined, in part, by incompletely understood local environmental
      factors. Bacterial signalling is likely to be a dominant influence on precursor
      cells when recruited to the mucosa. We assessed the influence of commensal
      bacteria on DC differentiation and function. Murine bone marrow progenitors were
      exposed to Lactobacillus salivarius, Bifidobacterium breve or Bifidobacterium
      infantis. Differences in cell surface phenotype and function were assessed.
      Myeloid differentiation factor 88(-/-) (MyD88) cells were used to determine the
      influence of Toll-like receptor signalling. While bacterial strains varied in
      impact, there was a consistent dose-dependent inhibition of DC differentiation
      with a shift toward a Gr-1(+) CD11b(+) monocyte-like phenotype. A single
      bacterium on a per cell basis (1 : 1) was sufficient to alter cell phenotype. The
      effect was only evident in early precursors. Enhanced interleukin-10 production
      correlated with increased Forkhead box P3 expression and reduced T-cell
      proliferation. The bacterial effect on DC differentiation was found to be MyD88
      dependent. Signalling by enteric commensals through pattern recognition receptors
      on precursor cells alters DC differentiation and results in cells that are
      phenotypically monocyte-like and functionally suppressive. This may account for
      some of the features of mucosal immune tolerance to the microbiota.

PMID- 19740343
TI  - The secreted form of p28 subunit of interleukin (IL)-27 inhibits biological
      functions of IL-27 and suppresses anti-allogeneic immune responses.
AB  - Interleukin-27 (IL-27) is a new IL-12-related heterodimeric cytokine comprising a
      novel p28 molecule and the Epstein-Barr-virus-induced gene 3 (EBI3) molecules. It
      augments initiation of T helper type 1-mediated immunity by enhancing the
      proliferation and cytokine production of T cells. In this study, we examined
      whether a secreted form of IL-27 subunits would inhibit IL-27-mediated
      immunological responses. COS-7 cells transduced with the mouse (m) p28 gene
      secreted a monomeric mp28 protein; however, those transduced with the mEBI3 gene
      did not detect a mEBI3 protein in the culture supernatants. The secreted mp28
      prevented the IL-27-mediated signal transduction and activator of transcription 1
      phosphorylation and subsequently inhibited the IL-27-mediated intercellular
      adhesion molecule-1 induction and interferon-gamma production in CD4(+) T cells.
      We generated mp28-expressing murine carcinoma Colon 26 cells and inoculated a
      mixture of the mp28- and mIL-27-expressing Colon 26 cells into syngeneic BALB/c
      mice. Simultaneous production of mp28 and mIL-27 from Colon 26 cells suppressed
      IL-27-mediated anti-tumour effects in the mice. We examined the p28-mediated
      immune suppression by inoculating mp28-expressing myoblasts into allogeneic mice.
      Forced production of mp28 suppressed the allogeneic cytotoxic T-lymphocyte
      induction and subsequently retarded the graft rejection. Furthermore, production
      of both mp28 and mp40, which inhibits the functions of IL-12 and IL-23, prolonged
      the graft survival longer than the grafts expressing either mp28 or mp40. We
      propose that p28 can be a regulatory subunit for IL-27-mediated cellular immune
      responses and a possible therapeutic agent to suppress unfavourable immune
      responses.

PMID- 19740344
TI  - Disequilibrium of T helper type 1, 2 and 17 cells and regulatory T cells during
      the development of experimental autoimmune myasthenia gravis.
AB  - Experimental autoimmune myasthenia gravis (EAMG), an animal model of myasthenia
      gravis (MG), is a rare organ-specific autoimmune disease targeting the
      autoantigen nicotinic acetylcholine receptor (AChR). We show here that the
      balance of T helper type 1 (Th1), Th2, Th17 and regulatory T (Treg) subsets of
      CD4(+) helper T cells were redistributed during the development of EAMG and that
      the interleukin-17 (IL-17) cytokine is involved in this disease. The ratio of
      Th17 cells changed most notably with disease progression accompanied by an up
      regulated level of IL-17. Moreover, the proliferative ability of AChR peptide
      specific T cells and the anti-AChR antibody-secreting cells increased when
      stimulated by IL-17 in vitro. These findings suggested that the disequilibrium of
      the CD4(+) helper T-cell subsets could promote the development of EAMG, and the
      pathogenic mechanism by which Th17 cells drives autoimmune responses by secreting
      cytokine IL-17 provides a new target for myasthenia gravis therapy.

PMID- 19740345
TI  - Modulation of dendritic cell maturation and function with mono- and bifunctional
      small interfering RNAs targeting indoleamine 2,3-dioxygenase.
AB  - Antigen-presenting cells expressing indoleamine 2,3-dioxygenase (IDO) play a
      critical role in maintaining peripheral tolerance. Strategies to inhibit IDO gene
      expression and enhance antigen-presenting cell function might improve anti-tumour
      immunity. Here we have designed highly effective anti-IDO small interfering (si)
      RNAs that function at low concentrations. When delivered to human primary immune
      cells such as monocytes and dendritic cells (DCs), they totally inhibited IDO
      gene expression without impairing DC maturation and function. Depending on the
      design and chemical modifications, we show that it is possible to design either
      monofunctional siRNAs devoid of immunostimulation or bifunctional siRNAs with
      gene silencing and immunostimulatory activities. The latter are able to knockdown
      IDO expression and induce cytokine production through either endosomal Toll-like
      receptor 7/8 or cytoplasmic retinoid acid-inducible gene 1 helicase. Inhibition
      of IDO expression with both classes of siRNAs inhibited DC immunosuppressive
      function on T-cell proliferation. Immature monocyte-derived DCs that had been
      transfected with siRNA-bearing 5'-triphosphate activated T cells, indicating
      that, even in the absence of external stimuli such as tumour necrosis factor
      alpha, those DCs were sufficiently mature to initiate T-cell activation.
      Collectively, our data highlight the potential therapeutic applications of this
      new generation of siRNAs in immunotherapy.

PMID- 19740346
TI  - Phthalate ester-induced thymic stromal lymphopoietin mediates allergic dermatitis
      in mice.
AB  - Recently air pollutants and irritants have been labelled as possible exogenous
      risk factors for allergic disorders. Although the underlying causes of allergic
      disorders such as atopic dermatitis and asthma remain unclear, the T helper type
      2 (Th2) cell-mediated allergic inflammatory cascade may contribute to their
      pathogenesis. In the last decade, it has been documented that one of the
      candidates for triggering Th2 commitment is thymic stromal lymphopoietin (TSLP),
      the expression of which is up-regulated in the lesions of allergic patients.
      Here, we describe TSLP function in a fluorescein isothiocyanate (FITC) -induced
      contact hypersensitivity (CHS) model. A cytokine profile indicated that the model
      was dominantly mediated by the Th2 milieu. Interestingly, TSLP was increased in
      the skin during the sensitization phase when stimulated by a solvent, dibutyl
      phthalate (DBP), but not by FITC hapten or another solvent, acetone. Ear swelling
      in FITC-induced CHS was totally abrogated by removing DBP from the sensitization
      or elicitation phase, and was restored by complementary injection of TSLP.
      Inversely, the ear swelling was suppressed by injection of small interfering RNA
      against TSLP during the sensitization phase, which was concomitant with
      decreasing expression of interleukin-4 at the swollen skin site. Taken together,
      DBP-induced TSLP during the sensitization phase plays a role in establishing FITC
      induced CHS and may be one of the causes of Th2 commitment in the model,
      suggesting that certain environmental toxins, such as DBP, may endow pro-allergic
      and atopic predisposition in humans or animals.

PMID- 19740347
TI  - Peptidoglycan from lactobacilli inhibits interleukin-12 production by macrophages
      induced by Lactobacillus casei through Toll-like receptor 2-dependent and
      independent mechanisms.
AB  - We previously showed that Lactobacillus strains having a rigid cell wall
      resistant to intracellular digestion can stimulate macrophages to induce large a
      quantity of interleukin-12 (IL-12). In this study, we examined the influence of
      lactobacilli and bacterial cell wall components on IL-12 production by
      macrophages that was induced by Lactobacillus casei, which has a rigid cell wall.
      Easily digestible lactobacilli such as Lactobacillus johnsonii and Lactobacillus
      plantarum or their intact cell walls (ICWs) weakly or very weakly induced IL-12
      production by macrophages, and inhibitedL. casei-induced IL-12 production. While
      the ICW of L. casei was resistant to intracellular digestion and did not inhibit
      L. casei-induced IL-12 production, its polysaccharide-depleted ICW, i.e. intact
      peptidoglycan, was sensitive to intracellular digestion and inhibited L. casei
      induced IL-12 production. Furthermore, the peptidoglycans of L. johnsonii, L.
      plantarum and Staphylococcus aureus also inhibited L. casei-induced IL-12
      production. Peptidoglycans from lactobacilli suppressed L. casei-induced
      expression of IL-12p40 but not IL-12p35 mRNA. Inhibition of IL-12 production by
      peptidoglycan was mitigated in Toll-like receptor 2 (TLR2)-deficient macrophages
      compared with the inhibition in wild-type macrophages. A derivative of the
      minimal structural unit of peptidoglycan (6-O-stearoyl-muramyl dipeptide)
      recognized by nucleotide-binding oligomerization domain 2 (NOD2) could also
      suppress L. casei-induced IL-12 production. These findings demonstrate that
      easily digestible bacteria and peptidoglycan suppress IL-12 production through
      pattern recognition receptors such as TLR2 and NOD2. IL-12 production in the gut
      may be negatively regulated by the simultaneous inhibitory actions of various
      resident bacteria that are susceptible to intracellular digestion.

PMID- 19740348
TI  - T cells as pioneers: antigen-specific T cells condition inflamed sites for high
      rate antigen-non-specific effector cell recruitment.
AB  - Cellular infiltration is a classic hallmark of inflammation. Whereas the role of
      T cells in many types of inflammation is well established, the specific impact of
      antigen recognition on their migration into the site and on the accumulation of
      other effector cells are still matters of debate. Using a model of an
      inflammatory effector phase driven by T-cell receptor (TCR) transgenic T cells,
      we found (i) that antigen-specific T cells play a crucial role as 'pioneer cells'
      that condition the tissue for enhanced recruitment of further T effector cells
      and other leucocytes, and (ii) that the infiltration of T cells is not dependent
      on antigen specificity. We demonstrate that a small number of antigen-specific T
      cells suffice to initiate a cascade of cellular immigration into the antigen
      loaded site. Although antigen drives this process, accumulation of T cells in the
      first few days of inflammation was not dependent on T-cell reactivity to the
      antigen. Both transgenic and wild-type T effector cells showed enhanced
      immigration into the site of antigen challenge after the initial arrival and
      activation of antigen-specific pioneer cells. This suggests that bystander
      accumulation of non-specific effector/memory T cells is a general feature in
      inflammation. Furthermore, tumour necrosis factor (TNF)-alpha and interferon
      (IFN)-gamma were identified as mediators that contribute to conditioning of the
      inflammatory site for high-rate accumulation of T effector cells in this T-cell
      driven model.

PMID- 19740349
TI  - Coadministration of the fungal immunomodulatory protein FIP-Fve and a tumour
      associated antigen enhanced antitumour immunity.
AB  - Fve is a fungal protein isolated from the golden needle mushroom Flammulina
      velutipes and has previously been reported to trigger immunological responses in
      both mouse and human lymphocytes. In this study, we evaluated the potential
      application of Fve as an adjuvant for tumour immunotherapy and examined the
      underlying mechanism(s). When the human papillomavirus (HPV)-16 E7 oncoprotein
      was used as a model antigen, mice coimmunized with HPV-16 E7 and Fve showed
      enhanced production of HPV-16 E7-specific antibodies as well as expansion of HPV
      16 E7-specific interferon (IFN)-gamma-producing CD4(+) and CD8(+) T cells as
      compared with mice immunized with HPV-16 E7 alone. Tumour protection assays
      showed that 60% of mice coimmunized with HPV-16 E7 plus Fve, as compared with 20%
      of those immunized only with HPV-16 E7, remained tumour-free for up to 167 days
      after challenge with the tumour cells. Tumour therapeutic assays showed that HPV
      16 E7 plus Fve treatment significantly prolonged the survival of tumour-bearing
      mice as compared with those treated only with HPV-16 E7. In vivo cell depletion
      and adoptive T-cell transfer assays showed that CD4(+) and CD8(+) T cells and IFN
      gamma played critical roles in conferring the antitumour effects. Interestingly,
      Fve could stimulate the maturation of splenic dendritic cells in vivo and induce
      antigen-specific CD8(+) T-cell immune responses. In summary, Fve has potent
      adjuvant properties that enhance T helper type 1 antigen-specific humoral and
      cellular immune responses which confer strong antitumour effects. The use of Fve
      as an adjuvant could be an attractive alternative to the current vaccination
      strategy for cancer immunotherapy.

PMID- 19740350
TI  - Mesangial cell complement receptor 1-related protein y limits complement
      dependent neutrophil accumulation in immune complex glomerulonephritis.
AB  - The absence of complement receptor 1 (CR1) related gene/protein y (Crry) leads to
      embryonic lethality as a result of unrestricted complement activation and
      concomitant neutrophil infiltration. Here we used Crry(-/-)C3(+/-) mice to
      investigate the role of Crry in the pathogenesis of immune complex
      glomerulonephritis (GN). After 3 weeks of immunization with horse spleen
      apoferritin, six of nine Crry(-/-) C3(+/-) mice and none of the six control C3(+/
      ) mice developed proliferative GN (P = 0.010). After 5 weeks of immunization, GN
      scores in Crry(-/-) C3(+/-) mice were 0.67 +/- 0.22 mean +/- standard error of
      the mean (SEM), compared with 0.32 +/- 0.16 in C3(+/-) mice. Glomerular
      hypercellularity was attributable to neutrophil infiltration in mice with GN (1.7
      +/- 0.3/glomerulus) compared with those without GN (0.4 +/- 0.1/glomerulus) (P =
      0.001). Absent staining for alpha-smooth muscle actin and proliferating cell
      nuclear antigen suggested that mesangial cell proliferation did not play a
      significant role in this model. Serum C3 levels in Crry(-/-) C3(+/-) mice were
      approximately 20% and 30% those of wild-type mice and C3(+/-) mice, respectively.
      To determine whether this acquired hypocomplementaemia was relevant to this GN
      model system, Crry(-/-) C3(+/-) mouse kidneys were transplanted into wild-type
      mice followed by immunization with apoferritin for 1 or 2 weeks. Surprisingly,
      none of the Crry(-/-) C3(+/-) mouse kidneys developed GN at these early time
      points, indicating that increasing circulating C3 levels several-fold did not
      increase susceptibility to GN. Renal expression of decay-accelerating factor was
      not different among any of the groups studied. Thus, our data indicate that
      mesangial cell Crry limits complement activation and subsequent neutrophil
      recruitment in the setting of local immune complex deposition.

PMID- 19740351
TI  - Identification and characterization of the interferon-beta-mediated p53 signal
      pathway in human peripheral blood mononuclear cells.
AB  - The relationship between the p53 signal pathway and the response of human
      peripheral blood mononuclear cells (PBMC) to interferon (IFN)-beta has hitherto
      not been examined. Using an oligonucleotide microarray, we found differential
      expression of at least 70 genes involved in the p53 signal pathway, including
      p53, which regulate cell proliferation and cell death following stimulation with
      IFN-beta. We verified our observations on a limited set of p53-regulated genes at
      the transcriptional and translational levels. We also examined the consequences
      of the activation of the p53 signal pathway by IFN-beta in PBMC. When cultured in
      the presence of T-cell mitogens, IFN-beta restricted the entry of lymphocytes
      from the G0/G1 phase to the S phase and reduced the number of cells in the G2
      phase. The addition of IFN-beta alone did not increase apoptosis. However, in the
      presence of actinomycin D, a DNA-damaging agent, addition of IFN-beta enhanced
      the susceptibility of PBMC to apoptosis. These observations suggest that, in
      spite of the activation of a number of mutually overlapping pathways mediating
      cell death, cell cycle arrest was the most evident consequence of IFN-beta
      signalling in PBMC.

PMID- 19740352
TI  - Diabetes mellitus and geriatric syndromes.
AB  - Diabetes mellitus is associated with an increased prevalence and incidence of
      geriatric syndrome: functional disabilities, depression, fall, urinary
      incontinence, malnutrition and cognitive impairment. Geriatric syndrome not only
      leads to frailty, loss of independence and low quality of life, but also becomes
      a major obstacle in the treatment and care of diabetic people. The risk factors
      or contributing factors of geriatric symptoms are micro- and macrovascular
      complications, age-rated comorbid disease and aging per se. Comprehensive
      geriatric assessment of geriatric syndrome, including basic activities of daily
      living, instrumental activities of daily living, gait and balance, visual acuity,
      the Mini-Mental State Examination, depression scores, history and risk of fall,
      urination and nutrition, should be performed as part of the care of elderly
      diabetic patients, in particular old-old patients. Because geriatric syndromes
      are multifactorial and share risk factors, diabetic people with any geriatric
      symptoms should be treated with a common concentric strategy, such as supervised
      exercise therapy including muscle-strengthening training, psychological support,
      social support for adherence, and good glycemic control with avoidance of
      hypoglycemia.

PMID- 19740353
TI  - Present status and perspectives regarding the therapeutic strategy for acute
      myeloid leukemia, non-Hodgkin's lymphoma and multiple myeloma in the elderly.
AB  - The incidence of cancers increases with advancing age. To improve the quality of
      life of elderly patients with hematological malignancies, appropriate therapeutic
      approaches have to be provided under adequate informed consent and with
      evaluation of the prognostic factors that predict the therapeutic outcome of each
      disease. Even in elderly patients, combination chemotherapies are effective for
      obtaining a good outcome for selected populations judged by factors such as
      performance status, pre-existing comorbid conditions or disease features;
      however, non-intensive treatment or supportive care might also be considered for
      patient groups with a poor prognosis. Therefore, the clinical parameters of the
      relevance for treatment decisions in the elderly are herein addressed. During
      cancer treatment, attention must be paid to the presence of age-related organ
      dysfunction, drug resistance, drug-induced side-effects such as end organ
      targeted toxicity, or neutropenia due to myelosuppression by cytotoxic drugs.
      Current therapeutic approaches are therefore expected to have good compliance and
      better outcome in elderly patients by the introduction of several molecularly
      targeted therapies, novel nucleoside analogs or non-myeloablative stem cell
      transplantation.

PMID- 19740354
TI  - Assessment of rolling walkers used by older adults in senior-living communities.
AB  - AIM: Rolling walkers (RW) are among the most common ambulatory devices used in
      senior-living communities. However, many observational studies have associated RW
      use with an increased risk of falling. Studies on how older RW users obtain and
      use their RW are lacking. Therefore, this study's purpose was to provide
      information about RW use that can aid clinical professionals in understanding how
      to educate RW users. METHODS: Data was gathered from 158 RW users (>or=65 years
      old) who had used their RW for an approximate mean of 24 months. Assessment
      utilized questionnaires, inspections and demonstrations. RESULTS: Almost 80% of
      all participants obtained an RW without consultation with a medical professional
      (61% through their own means; 19% through medical professionals without receiving
      instruction or demonstration). The most common misuse was incorrect RW height
      (55%). Maintenance problems were observed in approximately 17% of the RW. All
      users admitted that their walkers had not been rechecked by medical professionals
      since they had obtained them. Forward-leaning posture was apparent in
      participants during static standing (40%) and during ambulation (50%). Forward
      leaning posture during ambulation seemed to be more problematic in causing falls.
      CONCLUSION: Lack to consult a medical professional when obtaining an RW,
      incorrect RW height, poor RW maintenance and forward-leaning posture were
      problems commonly identified. This knowledge could assist medical professionals
      in implementing strategies to address these problems.

PMID- 19740355
TI  - Retrospective observational study of the incidence of short-term indwelling
      urinary catheters in elderly patients with neck of femur fractures.
AB  - BACKGROUND: 15-25% of general hospital admissions tend to involve patients that
      have had a short-term indwelling urinary catheter (IDC) inserted some time during
      their stay. There is little data on the specific incidence and complications of
      short-term urinary catheterization in elderly patients with neck of femur
      fractures. METHODS: Data was collected from the notes of 50 patients at Hemel
      Hempstead General Hospital with neck of femur fractures retrospectively from 31
      August 2007. Specific information on patient demographics, premorbid status,
      record and reason for urethral catheterization, place of insertion, gentamicin
      cover pre- and post-removal of IDC, residual volumes, duration of catheter
      insertion, catheter clamping prior to removal of IDC, urinary tract infection
      with IDC, post-IDC removal newly incontinent/in retention were collated from
      patient notes. Patients with prior chronic catheterization were excluded from the
      study. RESULTS: 78% of the patients had an IDC insertion (95% confidence
      interval, 64-88.4%). Most of the catheters were inserted on the ward (75%) with
      the rest being inserted mostly in theatre and recovery. Only approximately one
      third of the sample that had IDC inserted had residual volume documented in the
      notes. Of these patients, the majority had residual volume above 300 mL. The main
      reasons for IDC insertion were urinary retention (50%), incontinence (30.8%) and
      fluid monitoring (11.5%). Of the patients, 31.4% had documented urinary tract
      infection as a result of IDC insertion. CONCLUSION: This study revealed a higher
      incidence of short-term IDC insertion ( approximately 75%) in elderly patients
      with neck of femur fractures in comparison to general hospital admissions of 15
      25%. There is a role for more effective documentation in patient notes on the
      reasons behind urinary IDC insertion and increased clinical vigilance in
      preventing unnecessary catheterizations.

PMID- 19740356
TI  - Gerontology in the developing Brazil: achievements and challenges in public
      policies.
AB  - AIM: In the last three decades, the segment of population aged 60 years and older
      has more than doubled in Brazil. People aged 80 years and older are expected to
      be the fastest-growing segment in the near future. This aim of this study was to
      analyze the legal structures currently in place in Brazil and to provide a
      framework for care policies and practices towards older-adults. METHODS: This
      article focuses on past and present major socioeconomic burdens on this segment
      of the Brazilian population as well as on public achievements to overcome
      inequities. RESULTS: Both the public health and the social security systems have
      been directed to provide preferential assistance to the aged. Nonetheless, the
      elderly remain the most impoverished segment of Brazil and carry the burden of an
      overall lack of specialized services. Moreover, socioeconomic inequalities and
      population diversity in Brazil affects elderly care, adding complexity to this
      unique scenario. CONCLUSION: Brazil has adopted legal hallmarks that
      substantially shifted public practices towards the elderly segment from a
      philanthropic status to a legitimate right for care and assistance. The
      demographic transition that took place provides an opportunity for innovative
      solutions in public policies for older adults in a developing economic
      environment.

PMID- 19740357
TI  - Families' acceptance of near death: a qualitative study of the process for
      introducing end-of-life care.
AB  - AIM: Providing effective end-of-life (EOL) care for the elderly with severe brain
      damage is difficult because patients' families find it hard to accept the
      condition of their loved ones as "near death". In Japan, this has become an
      urgent social problem. Although health-care teams sometimes expect that the
      elderly with severe brain damage should be treated as terminal, many find that
      patients' families cannot accept the condition as near death. As a result, they
      are not able to appropriately introduce any EOL services. It was the aim of the
      present study to develop a comprehensive understanding of the process by which
      families accept the elderly with severe brain damage as near death. METHODS:
      Qualitative methodology with focus groups and semi-structured interviews were
      used. Twenty-three participants in two sets of male and female focus groups were
      interviewed in a semi-structured format. Ten participants (five men and five
      women) who made important medical decisions were then interviewed separately.
      RESULTS: Eleven categories emerged: (i) family affection with wishes for
      continued survival; (ii) vacillation of desire for death with dignity; (iii)
      family members' hierarchy; (iv) awareness that others may make different
      decisions; (v) family members' discussion overcoming discordance; (vi)
      satisfaction with physicians' explanations; (vii) impressions of life-sustaining
      measures; (viii) entrusting important decisions to hospital physicians; (ix)
      significance of family members' previous experiences; (x) patient's age; and (xi)
      duration of medical treatment. CONCLUSION: We developed a conceptual model that
      is useful for evaluating which stage of the process families are currently
      experiencing as well as introducing EOL care in a timely manner.

PMID- 19740358
TI  - B-type natriuretic peptide is predictive of hospitalization in community-dwelling
      elderly without heart diseases.
AB  - AIM: To examine prospectively the relationship between plasma B-type natriuretic
      peptide (BNP) levels in community-dwelling elderly and their hospitalization.
      METHODS: A total number of 644 subjects aged 65 years or older were recruited
      from the annual community health examinations. Those with a history of stroke or
      neurological findings were not included. After excluding those with old
      myocardial infarction, left ventricular dysfunction, moderate or severe valvular
      disorders, atrial fibrillation, renal insufficiency, and history of
      hospitalization within 1 year, 602 participants (226 men, 376 women; mean age,
      80.3 +/- 6.2 years) remained eligible for this study. Antihypertensive
      medications, activities of daily living (ADL) score and history of
      hospitalization were assessed by annual interview. Measurement of casual blood
      pressure, Mini-Mental State Examination, electrocardiography and echocardiography
      were performed. Plasma BNP, serum creatinine, total cholesterol, albumin and
      hemoglobin A1c levels were also examined. A follow-up survey was performed for
      the occurrence and reasons for hospitalization. RESULTS: During a median follow
      up of 37 months, 112 subjects were hospitalized. After adjustment for
      conventional risk factors of hospitalization using the Cox proportional hazard
      model, each increment of 1 standard deviation in log BNP levels was associated
      with a 36% increase in the risk of hospitalization (P = 0.02). Plasma BNP levels
      were significantly higher in the hospitalized subjects due to stroke, heart
      diseases, dementia, pneumonia and also difficulty to live alone than those of the
      subjects without hospitalization. CONCLUSION: Plasma BNP level is a very useful
      biochemical marker predictive of future hospitalization in community-dwelling
      independent elderly people without apparent heart diseases.

PMID- 19740359
TI  - Dental and radiographic findings as predictors of osteoporosis in postmenopausal
      women.
AB  - AIM: The objective of this study was to evaluate the relationship between dental
      findings and osteoporosis in postmenopausal women. METHODS: One hundred and eight
      postmenopausal women were recruited for the study. All participants underwent
      dual X-ray absorptiometry (DXA). The number of remaining teeth, clinical
      attachment loss, pocket depth and mobility of each tooth were determined.
      Radiodensitometric analyses were performed on digital periapical radiographs
      utilizing an aluminum stepwedge technique. The appearance of inferior mandibular
      cortex posterior of the mental foramina region was scored according to the
      classification by Klemetti. RESULTS: The number of remaining teeth, attachment
      loss values, Klemetti Index scores and the radiodensitometric scores showed a
      significant relationship with skeletal bone density. CONCLUSION: Tooth loss, an
      increased clinical attachment level, reduced density on digital periapical
      radiographs and an eroded appearance of the inferior mandibular cortex in
      panoramic radiographs are associated with low-skeletal bone mineral density.

PMID- 19740360
TI  - Sensory interaction on static balance: a comparison concerning the history of
      falls of community-dwelling elderly.
AB  - AIM: To determine whether elderly subjects with distinct histories of falls
      presented differences concerning the influence of sensory interaction on balance.
      METHODS: Cross-sectional research. Ninety-six community-dwelling elderly subjects
      were divided into three groups, according to the history of falls within the past
      year (group 1, no falls; group 2, one fall; and group 3, recurrent falls). The
      Clinical Test of Sensory Interaction and Balance was used to evaluate the
      influence of sensory inputs on standing balance. The test required the subject to
      maintain stability during 30 s, under six conditions: (i) firm surface with eyes
      open; (ii) firm surface with eyes closed; (iii) firm surface with visual
      conflict; (iv) unstable surface with eyes open; (v) unstable surface with eyes
      closed; and (vi) unstable surface with visual conflict. The time expended on
      conditions and the number of abnormal cases were compared between groups. Each
      group was evaluated in relation to its performance in the progression of
      conditions. RESULTS: More abnormal cases occurred in group 3 compared to group 1
      for conditions (iv) and (v); and compared to group 2 for condition (iv). Group 3
      remained less time than group 1 under conditions (iv), (v) and (vi). Groups 1, 2
      and 3 presented relevant decrements in trial duration from conditions (iv) to
      (v). For group 3, a significant decay was also noted from condition (i) to (ii).
      CONCLUSION: Sensorial interaction in the elderly varies according to their
      history of falls. Thus, it is possible to correctly guide the rehabilitation
      process and to prevent sensorial decays according to an individual's history of
      falls.

PMID- 19740361
TI  - Outcome and treatment in elderly patients with small cell lung cancer: a
      retrospective study.
AB  - AIM: The number of elderly patients with small cell lung cancer (SCLC) is
      expected to increase with the growing geriatric population. The aim of this study
      is to evaluate the safety and efficacy of standard chemotherapy or
      chemoradiotherapy in elderly patients with SCLC. METHODS: In this retrospective
      study, we analyzed the data of 126 patients with SCLC diagnosed between 1996 and
      2005 at our hospital, and compared the outcome of younger patients less than 70
      years and elderly patients 70 years or older who were treated with etoposide and
      cisplatin (EP regimen) and cyclophosphamide, adriamycin and vincristine (CAV
      regimen). Patients with limited disease SCLC received thoracic radiotherapy (RT)
      following chemotherapy. RESULTS: Overall response rates (complete and partial
      response) were not significantly different between patients less than 70 years
      and patients 70 years or older (69% vs 65%, P = 0.591). The median survival time
      was 13 months for patients less than 70 years compared with 12 months for
      patients 70 years or older (P = 0.263), with 2- and 5-year survival rates of
      37.8% and 8.2% vs 26.2% and 3.6%, respectively. Progression-free survival of
      patients 70 years or older was similar to that of patients less than 70 years (P
      = 0.445). Grade 3 and 4 hematological toxicities were more frequent among the
      elderly group (leukopenia, 48% vs 31%, P = 0.049; neutropenia, 52% vs 32%, P =
      0.028; thrombocytopenia, 38% vs 21%, P = 0.047). CONCLUSION: In spite of having
      more grade 3 and 4 hematological toxicity, elderly SCLC patients 70 years or
      older can benefit from the EP regimen and the CAV regimen with or without
      thoracic RT. Further investigations are needed to focus on ways to decrease
      toxicity, especially in the elderly.

PMID- 19740362
TI  - Combined effect of factors associated with burdens on primary caregiver.
AB  - BACKGROUND: It is argued that a multidimensional approach is necessary for burden
      assessment. Reducing caregiver burden is a social problem in the ageing Japan
      society. We examined the combined effect of factors affecting the care burden
      among community-dwelling handicapped people and their caregivers. METHODS: The
      participants were 49 handicapped people (aged 53-104 years) who received home
      visit rehabilitation, and their 49 caregivers (age 42-85 years). Caregivers were
      provided questionnaires consisting of questions on social support, subjective
      well-being, self-efficacy with regard to care continuation, the Motor Fitness
      Scale and caregiver burden. Care recipients were assessed using the Bedside
      Mobility Scale and the Barthel Index. RESULTS: We prepared the hypothesis model
      using structural equation modeling with the bootstrap method within outcome
      measures. The hypothesis model did not fit the data well. The impact of the Motor
      Fitness Scale was shifted from the caregiver burden to care self-efficacy and
      well-being, having a cooperator for care and variable of spouse caregiver or
      others associated with caregiver well-being in the revised model. The fit of the
      revised model was acceptable (goodness of fit index, 0.903; comparative fit
      index, 0.998; root mean square error of approximation, 0.017). In the revised
      model, the care recipients' disabled state was associated with caregiver burden.
      In addition, higher burden and poor motor fitness of caregivers might lead to
      lower care self-efficacy in providing continuous care and lower caregiver well
      being. CONCLUSION: These findings suggested that the program to reduce caregiver
      burden should focus on aspects of the care recipients' disabled state, the
      caregivers' well-being, fitness, and care self-efficacy.

PMID- 19740363
TI  - Asymptomatic leukocyturia and the autonomic nervous system in women.
AB  - BACKGROUND: The present study sought to investigate the relationship between
      asymptomatic leukocyturia (ASL) and autonomic nervous function by power spectral
      analysis of the R-R intervals in women. METHODS: One hundred and forty-two female
      outpatients aged 23-91 years were studied. We regarded ASL to be present if two
      consecutive samples were found to have 10 or more leukocytes/high-power field at
      x400 magnification in a centrifuged midstream urine sample. The R-R intervals of
      all subjects were measured by the wavelet transform analysis system. This system
      detected R-R variation data distributed in two bands: low-frequency power (LF)
      (0.04-0.15 Hz) and high-frequency power (HF) (0.15-0.40 Hz). The ratio of LF to
      HF (LF/HF) was also determined. Post-void residual urine volume was measured
      using an automated, compact 3-D ultrasound device. RESULTS: The patients with ASL
      had diabetes mellitus more frequently than those without ASL. Residual urine
      volume was significantly higher in the former than in the latter, while the HF
      values in both a recumbent position and a standing position were significantly
      lower in the former than in the latter (P = 0.003, P = 0.001, respectively).
      However, there were no significant differences in LF or LF/HF values in either a
      recumbent or a standing position between the two groups. The HF values in both a
      recumbent position and in a standing position were independent indicators of ASL,
      even after adjustment for age, diabetes mellitus and residual urine volume.
      CONCLUSION: The present study reveals the relationship between ASL and impairment
      of the parasympathetic nervous system in women.

PMID- 19740365
TI  - An animal model of compulsive food-taking behaviour.
AB  - The increase in the incidence of obesity and eating disorders has promoted
      research aimed at understanding the aetiology of abnormal eating behaviours.
      Apart from metabolic factors, obesity is caused by overeating. Clinical reports
      have led to the suggestion that some individuals may develop addictive-like
      behaviours when consuming palatable foods, and compulsive eating plays a similar
      dominant role in obesity as compulsive drug taking does in drug addiction. The
      progress made in the development of treatment strategies for obesity is limited,
      in part, because the physiological and neurological causes and consequences of
      compulsive eating behaviour are not clearly understood and cannot readily be
      studied in human subjects. We have developed experimental approaches that reflect
      the functioning of the components of eating control, including compulsive food
      taking in rats. Rats that are given free choice between standard chow and a
      palatable, chocolate-containing 'Cafeteria Diet' (CD) develop distinct signs of
      compulsive food taking that appear at an early stage. These include the inability
      to adapt intake behaviour in periods of limited or bitter-tasting CD access,
      continued food intake during resting phases and changes in fine structure of
      feeding (duration, distribution and recurrence of feeding bouts). The model will
      help examine the neurobiological underpinnings of compulsive food seeking and
      food taking and provides a possibility to study the effects of novel anti-obesity
      compounds on compulsive eating and other components of food-taking behaviour in
      detail. For future use of genetic models, the possibility of a transfer to a
      mouse was discussed.

PMID- 19740366
TI  - Compulsive alcohol drinking in rodents.
AB  - Upon prolonged alcohol exposure, the behaviour of an individual can gradually
      switch from controlled to compulsive. Our review is focused on the
      neurobiological mechanisms that might underlie this transition as well as the
      factors that are influencing it. Animal studies suggest that temporally increased
      alcohol consumption during post-abstinence drinking is accompanied by a loss of
      flexibility of the behaviour and therefore, could serve as a model for compulsive
      alcohol drinking. However, studies using different alcohol-preferring rat lines
      in the post-abstinence drinking model suggest that high alcohol consumption does
      not necessarily lead to the development of compulsive drinking. This indicates
      the significance of genetic predisposition to compulsive behaviour. Neuroimaging
      data show that chronic alcohol consumption affects the activity of several brain
      regions such as the extrapyramidal motor system and several areas of the
      prefrontal cortex including the orbitofrontal and anterior cingulate cortex.
      Similar changes in brain activity is seen in patients suffering from obsessive
      compulsive disorder at baseline conditions and during provocation of obsessive
      thoughts and urge to perform compulsive-like rituals. This indicates that
      dysfunction of these regions may be responsible for the expression of compulsive
      components of alcohol drinking behaviour. Several brain neurotransmitter systems
      seem to be responsible for the switch from controlled to compulsive behaviour. In
      particular, hypofunctioning of monoaminergic systems and hyperfunctioning of
      glutamatergic systems may play a role in compulsive alcohol drinking.

PMID- 19740367
TI  - Acquisition and reinstatement of MDMA-induced conditioned place preference in
      mice pre-treated with MDMA or cocaine during adolescence.
AB  - Those who take ecstasy are more likely to consume other drugs than non-users with
      cocaine abuse being reported by 75.5% of high school student MDMA (+/- 3,4
      methylenedioxymetamphetamine hydrochloride) users. The aim of this work was to
      evaluate the effects of exposure during adolescence to MDMA, cocaine or to both
      drugs on the MDMA-induced conditioned place preference (CPP) in adult mice.
      Animals received two daily administrations of saline, 10 mg/kg of MDMA, 25 mg/kg
      of cocaine or 10 mg/kg of MDMA plus 25 mg/kg of cocaine over 3 days (from PD28 to
      30). Three weeks after pre-treatment, the MDMA-induced CPP procedure was
      initiated (PD52). Acquisition of CPP was induced with a sub-threshold dose of
      MDMA (1.25 mg/kg) only in animals treated during adolescence with MDMA alone.
      Preference was established in all the groups after conditioning with 10 mg/kg of
      MDMA, while the time required to achieve extinction was longer in those pre
      treated with cocaine or MDMA alone (46 and 28 sessions, respectively). Moreover,
      preference was reinstated with progressively lower priming doses of MDMA in mice
      pre-treated with MDMA or cocaine alone. These results demonstrate that early
      exposure to MDMA or cocaine induces long-lasting changes that last until
      adulthood and modify the response of animals to MDMA.

PMID- 19740368
TI  - Preconscious attentional bias in cigarette smokers: a probe into awareness
      modulation on attentional bias.
AB  - It has been frequently reported that smokers showed attentional bias toward
      smoking-related stimuli. The current study aimed to examine whether such bias was
      also present when subjects were unaware of the presented stimuli and the possible
      role of awareness modulation on attentional bias. With a psychophysical approach
      (interocular suppression), we suppressed subjects' awareness to the cigarette
      pictures presented to one of their eyes. The visual dot probe task was modified
      to increase the perceptual load and to control the physical features between two
      rivaling images. Twenty-eight male smokers and 25 male non-smokers participated
      in the experiment. We found a significant interaction between experiment
      conditions and subject groups, with only the smoker group showed attentional bias
      toward cigarette pictures in unaware condition. Moreover, smokers' attentional
      bias in unaware condition was negatively correlated with their scores on
      Cigarette Dependence Scale while their attentional bias in aware condition was
      positively correlated with scores on Questionnaires of Smoking Urges. Such
      dissociation indicates the possibility of awareness modulation on attentional
      bias: it is possible that in aware condition, the attentional bias was modulated
      by smoking urge in awareness, thus concealed the effect of dependence degree.
      Further studies indicated that awareness modulated attentional bias through many
      factors, such as craving, quit attempt, attitude and disgust. Interestingly, non
      smokers also showed attentional bias in aware condition, which further suggested
      that due to awareness modulation, attentional bias could even be addiction
      unrelated.

PMID- 19740369
TI  - The interaction between the dopamine transporter gene and age at onset in
      relation to tobacco and alcohol use among 19-year-olds.
AB  - Recent evidence suggests that heterogeneity in the age at onset could explain the
      inconsistent findings of association studies relating the dopamine transporter
      (DAT1) gene with alcohol and nicotine consumption. The aim of this study was to
      examine interactions between two DAT1 polymorphisms and different initiation ages
      with regard to alcohol and tobacco consumption levels and dependence. Two hundred
      and ninety-one young adults (135 males, 156 females) participating in the
      Mannheim Study of Children at Risk were genotyped for the 40-bp variable number
      of tandem repeats (VNTR) and rs27072 polymorphisms of DAT1. Age at initiation was
      assessed at age 15 and 19 years. Information about current alcohol and tobacco
      consumption was obtained at age 19 years using self-report measures and
      structured interviews. Results suggest that age at onset of intensive consumption
      moderated the association of the DAT1 gene with early adult substance use and
      dependence, revealing a DAT1 effect only among individuals homozygous for the 10r
      allele of the 40-bp VNTR who had started daily smoking or being intoxicated early
      in life. Equally, carriers of the T allele of the rs27072 polymorphism reporting
      an early age at first intoxication showed higher current alcohol consumption at
      age 19 years. In contrast, no interaction between rs27072 and the age at first
      cigarette with regard to later smoking was observed. These findings provide
      evidence that the DAT1 gene interacts with an early heavy or regular drug
      exposure of the maturing adolescent brain to predict substance (ab)use in young
      adulthood. Further studies are required to confirm these findings.

PMID- 19740371
TI  - Cathepsin D activity protects against development of type AA amyloid fibrils.
AB  - BACKGROUND: The extracellular, fibrillar deposits of reactive (secondary)
      amyloidosis are composed of amyloid A (AA) protein, a proteolytically derived
      fragment of the acute phase protein serum amyloid A (SAA). While complete
      degradation of SAA precludes amyloid formation, limited cleavage which generates
      AA protein is considered part of the pathogenic mechanism. MATERIALS AND METHODS:
      In this study, we investigated SAA degradation by lysosomal enzymes cathepsins B,
      D, and K, and assessed the impact of cathepsin activity on AA amyloid formation
      in a cell culture model using peripheral blood mononuclear cells from healthy
      volunteers. RESULTS: Lysates of human mononuclear cells were capable of degrading
      SAA. Degradation was significantly reduced by inhibition of cathepsin D with
      pepstatin A. Inhibition of cathepsin B or cathepsin K, however, had no effect.
      The SAA fragment pattern generated by mononuclear cell lysates was similar to
      that produced by incubating SAA with purified human cathepsin D. Consistent with
      in vitro findings, amyloid formation in human monocyte cultures was increased by
      43% when cathepsin D was inhibited, but remained unaffected by inhibition of
      cathepsin B or cathepsin K. CONCLUSION: These data provide evidence that
      cathepsin D but not cathepsin B or cathepsin K is physiologically important in
      SAA degradation and hence in preventing SAA from accumulating and serving as
      precursor of AA amyloid fibrils.

PMID- 19740373
TI  - T-cell reconstitution without T-cell immunopathology in two models of T-cell
      mediated tissue destruction.
AB  - Antigen-specific T cells play a pivotal role in adaptive immune responses.
      However, they also contribute to the progression of a variety of diseases
      including autoimmune disorders, graft rejection and graft-versus-host disease
      (GVHD). Non-specific immune-ablation treatments compromise the ability of the
      host to respond to infection, whereas the selective removal of epitope-specific T
      cells could theoretically ameliorate T-cell-mediated pathology while preserving
      the rest of the host immune function. In this study we investigated whether it is
      possible to destroy specific unwanted antigen-specific T cells by incubating
      polyclonal T-cell populations with major histocompatibility complex (MHC)
      tetramers that are conjugated to the ribosomal-inactivating toxin, saporin. This
      strategy resulted in a dramatic reduction in the number of targeted antigen (Ag)
      specific CD8 T cells with no observable bystander toxicity in vitro. Moreover, in
      a model of transferable T-cell-dependent neurological disease induced by
      intracerebral (i.c.) lymphocytic choriomeningitis virus (LCMV) infection, the
      targeted killing of LCMV-specific CD8 T cells extended the survival of mice or
      fully prevented their death, depending on the dose of cells transferred. In
      addition, the tetramer- saporin conjugate also reduced liver damage in a model of
      donor T-cell-mediated hepatic destruction. These data provide a proof of
      principle that MHC tetramers could be exploited for the elimination or clinical
      manipulation of T-cell responses by linking effector molecules (a toxin in this
      case) to MHC tetramers. Also, the results suggest that it may be feasible to
      remodel T-cell responses, especially in immunocompromised hosts who receive
      adoptive cell transfers with many potential alloreactive cells.

PMID- 19740374
TI  - Discrimination between the main activating and inhibitory killer cell
      immunoglobulin-like receptor positive natural killer cell subsets using newly
      characterized monoclonal antibodies.
AB  - Natural killer (NK) cells are key components of the innate anti-viral and anti
      tumour immune responses. NK cell function is regulated by the interaction of
      killer cell immunoglobulin-like receptors (KIR) with human leucocyte antigen
      (HLA) class I molecules. In this study, we report on the generation of KIR
      specific antibodies allowing for discrimination between activating and inhibitory
      KIR. For this purpose, BALB/c mice were immunized with human KIR2DS2 recombinant
      protein. The precise specificity of KIR2DS2-specific clones was determined on KIR
      transfected BW cells and KIR-genotyped NK cells. When used in combination with
      EB6 (KIR2DL1/2DS1) or GL183 (KIR2DL2/2DL3/2DS2), two KIR-specific monoclonal
      antibodies (mAbs), 8C11 (specific for KIR2DL1/2DL2/2DL3/2DS2) and 1F12 (specific
      for KIR2DL3/2DS2), discriminated activating KIR2DS1 (8C11(-) EB6(+)) from
      inhibitory KIR2DL1 (8C11(+) GL183(-)) and KIR2DL2 (1F12(-) GL183(+)), while
      excluding the main HLA-Cw-specific KIR. Using these mAbs, KIR2DS1 was shown to be
      expressed on the surface of NK cells from all individuals genotyped as KIR2DS1(+)
      (n = 23). Moreover, KIR2DS1 and KIR2DL1 were independently expressed on NK cells.
      We also determined the amino acid position recognized by the 8C11 and 1F12 mAbs,
      which revealed that some KIR2DL1 allele-encoded proteins are not recognized by
      8C11. Because most available anti-KIR mAbs recognize both inhibitory and
      activating forms of KIR, these newly characterized antibodies should help assess
      the expression of activating and inhibitory KIR and their functional relevance to
      NK biology.

PMID- 19740372
TI  - Natural killer cells in infection and inflammation of the lung.
AB  - The lungs are a major site of entry of pathogens into the body and thus require
      rapid and effective innate responses to prevent pathogens establishing infection
      and to limit their spread. Additionally, the immune response in the lung must be
      tightly regulated such that pathogens are cleared, but immunopathology and
      chronic inflammation are prevented. In this review, I consider the role of
      natural killer (NK) cells in pulmonary infection and inflammation, specifically
      their contributions to influenza, tuberculosis, asthma and chronic obstructive
      pulmonary disease (COPD), which are major causes of morbidity and mortality world
      wide. Despite evidence of the importance of NK cells in these diseases, there are
      still major gaps in our understanding of how their function is regulated in this
      unique tissue environment. Understanding how different beneficial and detrimental
      effector functions of NK cells are triggered will be crucial if NK cells are to
      be exploited therapeutically in respiratory disease.

PMID- 19740375
TI  - Regulation of triggering receptor expressed on myeloid cells 1 expression on
      mouse inflammatory monocytes.
AB  - Triggering receptor expressed on myeloid cells 1 (TREM-1) is an activating
      receptor involved in inflammatory diseases and septic shock. The TREM-1 ligand(s)
      (TREM-1L) have not yet been identified. In this study, we performed a detailed
      analysis of the expression of mouse TREM-1 and its ligand(s). Our results
      demonstrate that TREM-1 is expressed on bone-marrow-derived dendritic cells
      (BMDC). On bone-marrow-derived macrophages (BMM) its expression is induced in
      vitro after stimulation by granulocyte-macrophage colony-stimulating factor,
      interleukin-3 or by myeloid differentiation primary response gene 88 (MyD88)
      dependent Toll-like receptor (TLR) ligands. Under steady-state conditions mouse
      TREM-1 is detectable on a Gr-1(-) F4/80(+) monocyte subpopulation bearing markers
      of resident monocytes, but not on Gr-1(+) F4/80(+) inflammatory monocytes. During
      lipopolysaccharide (LPS)-induced endotoxaemia TREM-1 was also up-regulated on
      inflammatory Gr-1(+) F4/80(+) cells in vivo. In tumour-bearing mice, TREM-1 was
      up-regulated on Gr-1(+) F4/80(+) monocytes, which phenotypically and functionally
      resembled mononuclear myeloid-derived suppressor cells. Using a soluble TREM-1
      fusion protein, we demonstrate that after intravenous injection of LPS TREM-1L
      was induced on Gr-1(+) granulocytes and monocytes but not on other cell
      populations in peripheral blood. This up-regulation on granulocytes was directly
      mediated by TLR ligands and required the adapter protein MyD88. In contrast to
      human, mouse platelets expressed TREM-1L neither under steady-state conditions
      nor after LPS injection in vivo. Our study reveals differential regulation of
      TREM-1 expression on mouse monocyte subpopulations and improves our understanding
      of the biological role of TREM-1 during disease.

PMID- 19740376
TI  - Junctional adhesion molecule (JAM)-B supports lymphocyte rolling and adhesion
      through interaction with alpha4beta1 integrin.
AB  - Junctional adhesion molecule-A (JAM-A), JAM-B and JAM-C have been implicated in
      leucocyte transmigration. As JAM-B binds to very late activation antigen (VLA)-4,
      a leucocyte integrin that contributes to rolling and firm adhesion of lymphocytes
      to endothelial cells through binding to vascular cell adhesion molecule (VCAM)-1,
      we hypothesized that JAM-B is also involved in leucocyte rolling and firm
      adhesion. To test this hypothesis, intravital microscopy of murine skin
      microvasculature was performed. Rolling interactions of murine leucocytes were
      significantly affected by blockade of JAM-B [which reduced rolling interactions
      from 9.1 +/- 2.6% to 3.2 +/- 1.2% (mean +/- standard deviation)]. To identify
      putative ligands, T lymphocytes were perfused over JAM-B-coated slides in a
      dynamic flow chamber system. JAM-B-dependent rolling and sticking interactions
      were observed at low shear stress [0.3 dyn/cm(2): 220 +/- 71 (mean +/- standard
      deviation) versus 165 +/- 88 rolling (P < 0.001; Mann-Whitney rank sum test) and
      2.6 +/- 1.3 versus 1.0 +/- 0.7 sticking cells/mm(2)/min (P = 0.026; Mann-Whitney
      rank sum test) on JAM-B- compared with baseline], but not at higher shear forces
      (1.0 dyn/cm(2)). As demonstrated by antibody blocking experiments, JAM-B-mediated
      rolling and sticking of T lymphocytes was dependent on alpha4 and beta1 integrin,
      but not JAM-C expression. To investigate whether JAM-B-mediated leucocyte
      endothelium interactions are involved in a disease-relevant in vivo model,
      adoptive transfer experiments in 2,4,-dinitrofluorobenzene (DNFB)-induced contact
      hypersensitivity reactions were performed in mice in the absence or in the
      presence of a function-blocking JAM-B antibody. In this model, JAM-B blockade
      during the sensitization phase impaired the generation of the immune response to
      DNFB, which was assessed as the increase in ear swelling in untreated, DNFB
      challenged mice, by close to 40% [P = 0.037; analysis of variance (anova)].
      Overall, JAM-B appears to contribute to leucocyte extravasation by facilitating
      not only transmigration but also rolling and adhesion.

PMID- 19740377
TI  - Correlation between recombinase activating gene 1 ubiquitin ligase activity and
      V(D)J recombination.
AB  - The really interesting new gene (RING) finger ubiquitin ligase domain of the
      recombinase activating gene 1 (RAG1) V(D)J recombinase protein adopts a standard
      cross-brace architecture but co-ordinates three zinc ions as opposed to the
      canonical two. We demonstrated previously that disruption of the conserved zinc
      co-ordination sites resulted in loss of structural integrity and ubiquitin ligase
      (E3) activity and interfered with the ability of full-length RAG1 to support
      recombination. Here we present evidence that amino acids surrounding the third,
      non-canonical site also contribute to functional interaction with the ubiquitin
      conjugating (E2) enzyme CDC34, while certain residues on the RING domain's
      surface important for interaction between other E2-E3 pairs are less critical to
      the functional RAG1-CDC34 interaction in this assay. Partial reduction of
      ubiquitin ligase activity was significantly correlated with reduction in the
      ability of RAG1 to support recombination of extra-chromosomal substrates (r =
      0.805, P = 0.009). While poly-ubiquitin chains could be generated, RAG1 did not
      promote rapid chain extension following mono-ubiquitylation of substrate,
      regardless of the E2 enzyme used. No single ubiquitin lysine mutant disrupted the
      ability of CDC34 to form ubiquitin chains on RAG1, and mass spectrometric
      analysis of the poly-ubiquitylated products indicated ubiquitin chain linkages
      through lysines 48 and 11. These data suggest that RAG1 promotes a mono
      ubiquitylation reaction that is required for optimal levels of V(D)J
      recombination.

PMID- 19740378
TI  - Binding immunoglobulin protein-treated peripheral blood monocyte-derived
      dendritic cells are refractory to maturation and induce regulatory T-cell
      development.
AB  - Binding immunoglobulin protein (BiP) has been shown previously to have
      immunomodulatory functions. Herein we investigated whether BiP could affect the
      differentiation of monocytes into dendritic cells (DCs) and thence the
      development of regulatory T cells. Peripheral blood monocyte-derived DCs were
      matured with lipopolysaccharide in the presence or absence of BiP. DC development
      and T-cell changes were monitored by flow cytometry and regulatory T-cell
      function was measured by uptake of tritiated thymidine. More BiP-treated DCs
      (DC((BiP))s) expressed amounts of intracellular indoleamine 2,3-dioxygenase (IDO)
      and cell surface leucocyte immunoglobulin-like receptor subfamily B member 1
      (LILRB1), retained CD14 expression but down-regulated expression of human
      leucocyte antigen (HLA)-DR and CD86, and produced copious amounts of interleukin
      (IL)-10, when compared with control DCs. T cells co-cultured with DC((BiP))s
      developed regulatory function with increased surface expression of CD4(+)
      CD25(hi) CD27(hi) but with no concomitant increase in forkhead box P3 (Foxp3).
      These T cells also showed significantly higher levels of intracellular cytotoxic
      T-lymphocyte antigen (CTLA)-4. The latter could be inhibited by the presence of
      the IDO inhibitor 1 methyl tryptophan. The addition of neutralizing anti-IL-10
      antibody or the specific mitogen-activated protein kinase (MAPK) p38 inhibitor
      SB203580 reversed the inhibition of DC differentiation by BiP. In conclusion, BiP
      is an immunomodulator able to arrest inflammation through induction of
      tolerogenic DCs and subsequent generation of T regulatory cells.

PMID- 19740379
TI  - Abnormal B-cell activation associated with TALL-1 over-expression and SOCS-1
      suppression during chronic hepatitis C virus infection.
AB  - Chronic hepatitis C virus (HCV) infection is associated with cirrhosis,
      autoimmunity and lymphoproliferative disorders. We have previously reported a
      differential regulation of T and B lymphocytes by HCV core protein in vitro. In
      this report, we employed a translational approach to characterize the activation
      status of peripheral B cells from individuals with chronic HCV infection and to
      explore potential mechanisms for B-cell dysregulation in the setting of HCV
      infection. In contrast to the T-cell suppression observed in HCV-infected
      individuals, B cells exhibit a non-specific polyclonal activation phenotype,
      characterized by significantly higher levels of (1) the early activation marker,
      CD69, (2) the costimulatory molecule, CD86, and (3) the CCR5 chemokine receptor,
      CD195, when compared with B cells from healthy donors in response to
      phytohaemagglutinin (PHA) stimulation. Importantly, tumour necrosis factor- and
      Apo-L-related leucocyte-expressed ligand-1 (TALL-1), also known as B-lymphocyte
      stimulator (BLYS), was found to be up-regulated on the surface of B cells from
      HCV patients in response to PHA as well as HCV core antigen stimulation. This up
      regulation of TALL-1 was associated with vigorous memory B-cell responses to
      viral antigenic stimulation. Additionally, suppressor of cytokine signalling-1
      (SOCS-1), a negative feedback immunoregulator that is inhibited in B lymphocytes
      by HCV core in vitro, was also inhibited in B cells from HCV patients when
      compared with healthy donors. These findings suggest that TALL-1 over-expression
      and SOCS-1 suppression are associated with aberrant B-cell activation, providing
      a plausible basis for the B-cell clonal expansion underlying the
      lymphoproliferative disorders and autoimmune phenomena observed during chronic
      HCV infection.

PMID- 19740380
TI  - Chimeric IgG4 PR3-ANCA induces selective inflammatory responses from neutrophils
      through engagement of Fcgamma receptors.
AB  - Anti-proteinase 3 antibodies are implicated in the pathogenesis of small vessel
      vasculitis. These are primarily immunoglobulin G (IgG), with different subclasses
      predominating at different stages of disease. However, little is known of their
      respective roles in pathogenesis. We have previously shown that patient IgG4 was
      able to induce superoxide release from human neutrophils. To circumvent
      difficulties in separating the subclasses and additional differences in
      polyclonal patient antibodies we have generated monoclonal mouse/human IgG1 and
      IgG4 anti-proteinase 3 antibodies. Using these antibodies we have compared
      effects of IgG1 and IgG4 on human neutrophils in terms of superoxide release,
      cytokine production, degranulation and adhesion. Additionally we have
      investigated the interaction of the subclasses with Fc receptors expressed by the
      neutrophil. Chimeric antibodies were generated using human constant regions of
      each subclass and a variable region taken from a monoclonal antibody directed
      against proteinase 3. Superoxide release from neutrophils was measured by the
      reduction of ferricytochrome C, degranulation by the conversion of a synthetic
      colour substrate, cytokine release by interleukin-8 enzyme-linked immunosorbent
      assay, and adhesion by a flow-based adhesion assay. Fc receptor binding was
      assessed using blocking antibodies. The IgG4 anti-proteinase 3 was able to induce
      a dose-dependent release of superoxide, degranulation and adhesion. The antibody
      was not able to stimulate the secretion of interleukin-8. Fc receptors were
      essential for neutrophil stimulation and the constitutive Fc receptors were
      necessary for different stimulatory pathways. The IgG4 anti-proteinase 3
      antibodies are able to stimulate neutrophils to undergo a pro-inflammatory
      response and may play a role in the pathogenesis of small vessel vasculitis.

PMID- 19740381
TI  - A tolerogenic peptide down-regulates mature B cells in bone marrow of lupus
      afflicted mice by inhibition of interleukin-7, leading to apoptosis.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease mediated by T and B
      cells. It is characterized by a variety of autoantibodies and systemic clinical
      manifestations. A tolerogenic peptide, designated hCDR1, ameliorated the
      serological and clinical manifestations of SLE in both spontaneous and induced
      models of lupus. In the present study, we evaluated the status of mature B cells
      in the bone marrow (BM) of SLE-afflicted mice, and determined the effect of
      treatment with the tolerogenic peptide hCDR1 on these cells. We demonstrate
      herein that mature B cells of the BM of SLE-afflicted (New Zealand Black x New
      Zealand White)F(1) mice were largely expanded, and that treatment with hCDR1 down
      regulated this population. Moreover, treatment with hCDR1 inhibited the
      expression of the pathogenic cytokines [interferon-gamma and interleukin (IL)
      10], whereas it up-regulated the expression of transforming growth factor-beta in
      the BM. Treatment with hCDR1 up-regulated the rates of apoptosis of mature B
      cells. The latter was associated with inhibited expression of the survival Bcl-xL
      gene and of IL-7 by BM cells. Furthermore, the addition of recombinant IL-7
      abrogated the suppressive effects of hCDR1 on Bcl-xL in the BM cells and resulted
      in elevated levels of apoptosis. Hence, the down-regulated production of IL-7
      contributes to the hCDR1-mediated apoptosis of mature B cells in the BM of SLE
      afflicted mice.

PMID- 19740382
TI  - Impaired macrophage function following bacterial stimulation in chronic
      granulomatous disease.
AB  - Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is critical for
      phagocyte anti-microbial activity and plays a major role in innate immunity.
      Defects in genes coding for components of the NADPH oxidase enzyme system are
      responsible for chronic granulomatous disease (CGD), a rare primary neutrophil
      immunodeficiency associated with recurrent, life-threatening bacterial and fungal
      infections. Microbial killing and digestion within the neutrophil phagosomal
      compartment are defective in these patients. NADPH oxidase activity is also
      crucial for optimal macrophage and dendritic cell function and has recently been
      implicated in both cross-presentation and T-cell priming. We present evidence of
      impaired macrophage function in CGD, with attenuated pro-inflammatory cytokine
      and increased interleukin-10 secretion following bacterial stimulation. These
      results highlight additional abnormalities in macrophage function associated with
      CGD and the importance of NADPH oxidase activity in immunity.

PMID- 19740383
TI  - Investigation of the mechanism of action of alemtuzumab in a human CD52
      transgenic mouse model.
AB  - Alemtuzumab is a humanized monoclonal antibody against CD52, an antigen found on
      the surface of normal and malignant lymphocytes. It is approved for the treatment
      of B-cell chronic lymphocytic leukaemia and is undergoing Phase III clinical
      trials for the treatment of multiple sclerosis. The exact mechanism by which
      alemtuzumab mediates its biological effects in vivo is not clearly defined and
      mechanism of action studies have been hampered by the lack of cross-reactivity
      between human and mouse CD52. To address this issue, a transgenic mouse
      expressing human CD52 (hCD52) was created. Transgenic mice did not display any
      phenotypic abnormalities and were able to mount normal immune responses. The
      tissue distribution of hCD52 and the level of expression by various immune cell
      populations were comparable to those seen in humans. Treatment with alemtuzumab
      replicated the transient increase in serum cytokines and depletion of peripheral
      blood lymphocytes observed in humans. Lymphocyte depletion was not as profound in
      lymphoid organs, providing a possible explanation for the relatively low
      incidence of infection in alemtuzumab-treated patients. Interestingly, both
      lymphocyte depletion and cytokine induction by alemtuzumab were largely
      independent of complement and appeared to be mediated by neutrophils and natural
      killer cells because removal of these populations with antibodies to Gr-1 or
      asialo-GM-1, respectively, strongly inhibited the activity of alemtuzumab whereas
      removal of complement by treatment with cobra venom factor had no impact. The
      hCD52 transgenic mouse appears to be a useful model and has provided evidence for
      the previously uncharacterized involvement of neutrophils in the activity of
      alemtuzumab.

PMID- 19740384
TI  - Beta(2) integrin deficiency yields unconventional double-negative T cells
      distinct from mature classical natural killer T cells in mice.
AB  - Expressed on leucocytes, beta(2) integrins (CD11/CD18) are specifically involved
      in leucocyte function. Using a CD18-deficient (CD18(-/-)) mouse model, we here
      report on their physiological role in lymphocyte differentiation and trafficking.
      CD18(-/-) mice present with a defect in the distribution of lymphocytes with
      highly reduced numbers of naive B and T lymphocytes in inguinal and axillary
      lymph nodes. In contrast, cervical lymph nodes were fourfold enlarged harbouring
      unconventional T-cell receptor-alphabeta (TCR-alphabeta) and TCR-gammadelta
      CD3(+) CD4(-) CD8(-) (double-negative; DN) T cells that expanded in situ. Using
      adoptive transfer experiments, we found that these cells did not home to
      peripheral lymph nodes of CD18(wt) recipients but, like antigen-experienced T or
      natural killer (NK) T cells, recirculated through non-lymphoid organs. Lacking
      regulatory functions in vitro, CD18(-/-) TCR-alphabeta DN T cells did not
      suppress the proliferation of polyclonally activated CD4(+) or CD8(+) (single
      positive; SP) T cells. Most interestingly, CD18(-/-) TCR-alphabeta DN T cells
      showed intermediate TCR expression levels, an absent activation through
      allogeneic major histocompatibility complex and a strong proliferative dependence
      on interleukin-2, hence, closely resembling NKT cells. However, our data oppose
      former reports, clearly showing that, because of an absent reactivity with CD1d
      alphaGalCer dimers, these cells are not mature classical NKT cells. Our data
      indicate that CD18(-/-) TCR-alphabeta DN T cells, like NKT and TCR-gammadelta T
      cells, share characteristics of both adaptive and innate immune cells, and may
      accumulate as a compensatory mechanism to the functional defect of adaptive
      immunity in CD18(-/-) mice.

PMID- 19740385
TI  - Clone clusters in autoreactive CD4 T-cell lines from probable multiple sclerosis
      patients form disease-characteristic signatures.
AB  - We developed a method for selectively propagating disease-related autoreactive T
      cell lines (auTCLs) based on their increased resistance to apoptosis. The
      generated auTCLs homogeneously co-express CD45RO and CD49a, adhere strongly to
      extracellular matrix proteins and express high interleukin-17 (IL-17) messenger
      RNA levels, resembling a T-cell subset proposed to transmigrate into tissues and
      induce systemic and local inflammation in rheumatoid arthritis. The combinations
      of T-cell oligoclones that comprise probable multiple sclerosis (pMS) disease
      related lines use a unique portfolio of T-cell receptor beta-chain variable
      allele (BV genes) combinations forming 'disease-specific cluster patterns'. The
      auTCL derived from different patients and from different myelin epitopes display
      striking similarities in BV gene allele clusters and are derived primarily from a
      disease-prone hotspot residing in the BV gene locus between Vbeta6 and Vbeta9.
      Conversely, healthy subject TCLs use different BV gene allele sets, forming
      'healthy responder usage formats'. These formats were absent from the pMS patient
      V-beta gene allele combinations evaluated in this study. Hierarchical clustering
      of the BV gene combinations, distinguish three pMS auTCL groups, implying
      existence of up to three disease-related immune response patterns. These subgroup
      patterns may reflect different disease subclasses or alternatively they may
      suggest immune reactivity to different aetiological agents. Analyses of clonal
      clustering patterns may potentially aid in subclassification of MS or in
      characterizing aetiological agents of this disease.

PMID- 19740386
TI  - Response of macrophage Toll-like receptor 4 to a Sporothrix schenckii lipid
      extract during experimental sporotrichosis.
AB  - Toll-like receptors have been implicated in the recognition of various pathogens,
      including bacteria, viruses, protozoa and fungi. However, no information is
      available about Toll-like receptor 4 (TLR4) participation in Sporothrix schenckii
      recognition and the consequent triggering of the immune response to this fungal
      pathogen. Following activation of TLRs by ligands of microbial origin, several
      responses are provoked, including reactions in immune cells that may lead them to
      produce signalling factors that trigger inflammation. The present study was
      designed to elucidate the role of TLR4 during the host response to S. schenckii.
      TLR4-deficient (C3H/HeJ) and control mice (C3H/HePas) were infected with S.
      schenckii yeast cells and immune response was assessed over 10 weeks by assaying
      production of pro-inflammatory mediator (nitric oxide and tumour necrosis factor
      alpha) and anti-inflammatory cytokine (interleukin-10) by peritoneal macrophages
      and their correlation with apoptosis in peritoneal exudate cells. We found that
      both pro-inflammatory and anti-inflammatory mediators are reduced in TLR4
      deficient mice, suggesting the involvement of this receptor in the recognition of
      this infectious agent. Translocation into the nucleus of nuclear transcription
      factor, nuclear factor-kappaB, was also evaluated and showed higher levels in TLR
      4 normal mice, consistent with the results found for cytokine production. We are
      showing here, for the first time, the involvement of TLR4 in S. schenckii
      recognition. Taken together, our results demonstrate that the activation of
      peritoneal macrophages in response to S. schenckii lipid extracts has different
      responses in these two mouse strains which differ in TLR4 expression, suggesting
      an important role for TLR4 in governing the functions of macrophages in this
      fungal infection.

PMID- 19740387
TI  - How it works.

PMID- 19740388
TI  - Eculizumab.

PMID- 19740389
TI  - Trabectedin.

PMID- 19740390
TI  - Assessing efficacy of non-opioid analgesics in experimental pain models in
      healthy volunteers: an updated review.
AB  - AIM: Experimental pain models may help to evaluate the mechanisms of analgesics
      and target the clinical indications for their use. This review, the second in a
      series of two, addresses how the efficacy of non-opioid analgesics have been
      assessed in human volunteers using experimental pain models. METHODS: A
      literature search was completed for randomized controlled studies that included
      human experimental pain models, healthy volunteers and non-opioid analgesics.
      RESULTS: Nonsteroidal anti-inflammatory drugs worked against various types of
      acute pain as well as in hyperalgesia. Analgesia from paracetamol was difficult
      to detect in experimental pain and the pain needed to be assessed with very
      sensitive methods like evoked brain potentials. The N-methyl-D-aspartate
      antagonists exemplified by ketamine generally needed strong, long-lasting or
      repeated pain in the skin for detectable analgesia, whereas pain in muscle and
      viscera generally was more easily attenuated. Gabapentin worked well in several
      models, particularly those inducing hyperalgesia, whereas lamotrigine was weak in
      modulation of experimental pain. Imipramine attenuated pain in most experimental
      models, whereas amitriptyline had weaker effects. Delta-9-tetrahydrocannabinol
      attenuated pain in only a few models. CONCLUSIONS: Pain induction and assessment
      are very important for the sensitivity of the pain models. Generally,
      experimental pain models need to be designed with careful consideration of the
      pharmacological mechanisms and pharmacokinetics of analgesics. The drawback with
      the different study designs is also discussed. This knowledge can aid the
      decisions that need to be taken when designing experimental pain studies for
      compounds entering Phase I and II trials.

PMID- 19740391
TI  - The use of gastrointestinal intubation studies for controlled release
      development.
AB  - AIMS: This review describes clinical results of gastrointestinal intubation
      studies of eight controlled release (CR) candidates under development during the
      1990s and offers suggestions for determining why, when and how to conduct human
      intubation studies. METHODS: Experience with the administration of the following
      eight compounds to various regions of the gastrointestinal tract is described: CJ
      13,610, CP-195,543, CP-331,684, CP-409,092, CP-424,391, azithromycin, sertraline,
      and trovafloxacin. Also included are human pharmacokinetic studies with prototype
      CR dosage forms for CJ-13,610 and CP-424,391. RESULTS: Intubation studies, while
      appearing invasive, are safe and not unpleasant procedures that have been found
      to be valuable in the development of CR formulations. CONCLUSIONS: The following
      recommendations are made regarding intubation studies: (i) no intubation study is
      recommended for compounds with high permeability, since these compounds are
      likely to be well absorbed from the colon; (ii) compounds with moderate
      permeability may require an intubation study if the dog colon and in silico
      models predict a marginally acceptable CR concentration-time profile; (iii) use a
      dose that approximates 1 h of the intended CR delivery rate; (iv) use the
      smallest volume possible; (v) define and record tubing placement; (vi) use a
      thermodynamically stable solution or/and suspension.

PMID- 19740392
TI  - Maraviroc modelling strategy: use of early phase 1 data to support a semi
      mechanistic population pharmacokinetic model.
AB  - AIMS: To model the basic pharmacokinetic (PK) characteristics of maraviroc to
      construct an integrated semi-mechanistic PK model for use in later population PK
      analyses. METHODS: Three analyses were performed utilizing intravenous, oral and
      radiolabel data. Firstly, a PK disposition model was developed from data from 20
      healthy males who received 3, 10 or 30 mg of intravenous maraviroc. Secondly, a
      sigmoid E(max)vs dose model of dose-normalized non-compartmental AUC from oral
      dosing in 134 healthy young males and females across five phase 1 studies was
      constructed. This described absorption dose non-linearities and tested for the
      influence of food, formulation and dose frequency on model parameters. The third
      analysis developed a mass balance model for both absorption and disposition of
      maraviroc with 300 mg solution and predicted the mass balance after
      administration of 100 mg tablet formulation. RESULTS: A four-compartment PK model
      best described the intravenous data and no influence of dose was found on
      clearance. Total clearance was 48 l h(-1) (2.2% SE). The main covariate effect in
      the non-compartmental analysis reproduced the dose-dependency of food through a
      five-fold increase in the ED(50) of the sigmoid E(max) model. The mass balance
      models calculated that 33.3% and 22.9% of 300 mg solution and 100 mg tablet
      doses, respectively, are systemically available, and first-pass metabolism
      extracts 62% of an absorbed dose, estimating a hepatic blood flow of 101 l h(-1).
      CONCLUSIONS: The analysis demonstrates a novel integration approach to build a
      maraviroc semi-mechanistic population PK model for further use in volunteers and
      patients.

PMID- 19740393
TI  - Effect of a proton pump inhibitor on the pharmacokinetics of imatinib.
AB  - AIMS: Imatinib mesylate (Gleevec/Glivec), which has revolutionized the treatment
      of chronic myeloid leukemias (CML) and gastrointestinal stromal tumours (GIST),
      has been reported to cause gastric upset. Consequently, proton pump inhibitors
      (PPI) are frequently co-administered with imatinib. Because PPI can elevate
      gastric pH and delay gastric emptying or antagonize ATP-binding-cassette
      transporters, they could influence imatinib absorption and pharmacokinetics. We
      aimed to evaluate whether use of omeprazole has a significant effect on imatinib
      pharmacokinetics. METHODS: Twelve healthy subjects were enrolled in a two-period,
      open-label, single-institution, randomized cross-over, fixed-schedule study. In
      one period, each subject received 400 mg imatinib orally. In the other period, 40
      mg omeprazole (Prilosec) was administered orally for 5 days, and on day 5 it was
      administered 15 min before 400 mg imatinib. Plasma concentrations of imatinib and
      its active N-desmethyl metabolite CGP74588 were assayed by LC-MS, and data were
      analyzed non-compartmentally. RESULTS: PPI administration did not significantly
      affect the imatinib area under the plasma concentration vs time curve (AUC) (34.1
      microg ml(-1) h alone vs 33.1 microg ml(-1) h with omeprazole, P= 0.64; 80%
      power), maximum plasma concentration (C(max)) (2.04 microg ml(-1) alone vs 2.02
      microg ml(-1) with omeprazole, P= 0.97), or half-life (13.4 h alone vs 14.1 h
      with omeprazole, P= 0.13). CONCLUSIONS: Our results indicate that the use of
      omeprazole does not significantly affect the pharmacokinetics of imatinib, as
      opposed to, for example, dasatinib where PPI decreased AUC and C(max) two-fold.

PMID- 19740394
TI  - Intracellular 'boosting' of darunavir using known transport inhibitors in primary
      PBMC.
AB  - AIMS: ABCB1, some ABCCs and SLCOs have been reported to affect the intracellular
      accumulation of various protease inhibitors in vitro and ex vivo. Darunavir is
      the most recently licensed protease inhibitor and we sought to investigate the
      ability of transport inhibitors to influence its intracellular accumulation in
      lymphocytes from healthy volunteers. METHODS: The intracellular accumulation of
      radiolabelled darunavir was assessed using CEM cells and ABCB1-overexpressing
      CEM(VBL) cells. Apical and basolateral transport of radiolabelled darunavir
      through MDCKII monolayers was also studied. Finally the ability of known
      inhibitors to influence intracellular accumulation of darunavir in peripheral
      blood mononuclear cells (PBMC) was investigated. RESULTS: CEM(VBL) cells (1.4 +/-
      0.6, P < 0.001, 95% CI for the difference = 0.46, 0.80, n= 7) had significantly
      lower accumulation of darunavir compared with CEM cells (5.6 +/- 0.7, n= 7) and
      this was reversed by addition of tariquidar (30 nm, 4.6 +/- 0.8, P < 0.001, 95%
      CI =-0.64, -0.41, n= 4). In MDCKII-ABCBI cells, transport from the basal to the
      apical compartment was observed and this was also reversible with the addition of
      tariquidar. In PBMCs, dipyridamole (6.9 +/- 1.3, P < 0.01, 95% CI for the
      difference =-1.16, -0.30, (n= 8) significantly increased whilst montelukast (5.7
      +/- 1.0, P < 0.01, 95% CI for the difference = 0.16, 0.79, n= 8) significantly
      decreased the intracellular accumulation of darunavir when compared with control
      (6.2 +/- 1.1, n= 8). CONCLUSIONS: Darunavir is a substrate for efflux and influx
      transporters in PBMC and intracellular concentrations can be manipulated using
      known inhibitors.

PMID- 19740395
TI  - The effect on sotrastaurin pharmacokinetics of strong CYP3A inhibition by
      ketoconazole.
AB  - AIMS: Sotrastaurin is an immunosuppressant that reduces T-lymphocyte activation
      via protein kinase C inhibition. The effect of CYP3A4 inhibition by ketoconazole
      on the pharmacokinetics of sotrastaurin, a CYP3A4 substrate, was investigated.
      METHODS: This was a two-period, single-sequence crossover study in 18 healthy
      subjects. They received a single 50 mg oral dose of sotrastaurin in period 1
      followed by a 14-day inter-treatment phase. In period 2 they received
      ketoconazole 200 mg twice daily for 6 days and a single 50 mg dose of
      sotrastaurin on the fourth day of ketoconazole administration. RESULTS: Co
      administration of single-dose sotrastaurin during steady-state ketoconazole
      increased sotrastaurin C(max) by 2.5-fold (90% confidence interval 2.2, 2.9) from
      285 +/- 128 to 678 +/- 189 ng ml(-1) and increased AUC by 4.6-fold (4.1, 5.2)
      from 1666 +/- 808 to 7378 +/- 3011 ng ml(-1) h. Sotrastaurin half-life was nearly
      doubled from 5.9 +/- 1.7 to 10.6 +/- 2.5 h. The AUC of the active metabolite N
      desmethyl-sotrastaurin was increased by 6.8-fold. Sotrastaurin did not alter
      ketoconazole steady-state predose plasma concentrations. CONCLUSIONS: The strong
      CYP3A4 inhibitor ketoconazole increased sotrastaurin AUC by 4.6-fold. A
      compensatory reduction in the dose of sotrastaurin is warranted when strong
      CYP3A4 inhibitors are co-administered.

PMID- 19740396
TI  - Influence of transdermal rotigotine on ovulation suppression by a combined oral
      contraceptive.
AB  - AIMS: To assess the influence of the transdermally applied dopamine agonist
      rotigotine on ovulation suppression by a combined oral contraceptive (0.03 mg
      ethinyloestradiol and 0.15 mg levonorgestrel) in a randomized, double-blind
      crossover study in 40 healthy females. METHODS: Treatment A consisted of the
      combined oral contraceptive for 28 days plus rotigotine for the first 13 days (2
      mg (24 h)(-1) on days 1-3, 3 mg (24 h)(-1) maintenance dose thereafter). During
      treatment B, subjects received matching placebo patches instead of rotigotine.
      Pharmacodynamic parameters (progesterone, oestradiol, luteinizing hormone, and
      follicle stimulating hormone serum concentrations), pharmacokinetic parameters
      for ethinyloestradiol/levonorgestrel and rotigotine, and safety and tolerability
      of the treatment were assessed. RESULTS: Progesterone serum concentrations
      remained below 2 ng ml(-1) in all subjects during the luteal phase. Median serum
      concentrations of all other pharmacodynamic parameters were similar during both
      treatments. Pharmacokinetic parameters C(max,ss) and AUC(0,24 h)(ss) at steady
      state were similar with or without co-administration of rotigotine for both
      ethinyloestradiol and levonorgestrel with geometric mean ratios close to 1 and
      90% confidence intervals within the acceptance range of bioequivalence (0.8,
      1.25): C(max,ss) 1.05 (0.93, 1.19), AUC(0,24 h)(ss) 1.05 (0.9, 1.22) for
      ethinyloestradiol; C(max,ss) 1.01 (0.96, 1.06), AUC(0,24 h)(ss) 0.98 (0.95, 1.01)
      for levonorgestrel. Mean plasma concentrations of unconjugated rotigotine
      remained stable throughout the patch-on period (day 13). CONCLUSIONS: Concomitant
      administration of 3 mg (24 h)(-1) transdermal rotigotine had no impact on the
      pharmacodynamics and pharmacokinetics of a combined oral contraceptive containing
      0.03 mg ethinyloestradiol and 0.15 mg levonorgestrel, suggesting that the
      dopamine agonist does not influence contraception efficacy.

PMID- 19740397
TI  - Influence of ABCB1 gene polymorphisms on the pharmacokinetics of verapamil among
      healthy Chinese Han ethnic subjects.
AB  - AIMS: To assess the association between polymorphisms of the ABCB1 gene and the
      pharmacokinetics of verapamil among healthy Chinese Han ethnic subjects. METHODS:
      Based on polymorphisms of the ABCB1 gene at positions 2677 and 3435, 24 healthy
      male participants were divided into three groups: 2677GG/3435CC (n = 6),
      2677GT/3435CT (n = 12) and 2677TT/3435TT (n = 6). Each subject had received a
      single oral dose of verapamil (80 mg) under fasting conditions. Multiple blood
      samples were collected over 24 h, and plasma concentrations of verapamil were
      determined by HPLC. Pharmacokinetic characteristics were compared between the
      different genotypic groups. RESULTS: The pharmacokinetics parameters of verapamil
      differed significantly among the three genotypic groups. AUC(last) was
      significantly lower among individuals with the 2677TT/3435TT (159.5 +/- 79.0 ng
      ml(-1) h) and 2677GT/3435CT (189.3 +/- 73.1 ng ml(-1) h) genotypes than those
      with the 2677GG/3435CC genotype (303.1 +/- 83.7 ng ml(-1) h) (P= 0.004 and P=
      0.008, respectively). However, the CL/F value was higher among subjects with the
      2677TT/3435TT (523.0 +/- 173.7 l h(-1)) genotype than those with the
      2677GT/3435CT (452.2 +/- 188.6 l h(-1)) or 2677GG/3435CC (265.4 +/- 72.8 l h(-1))
      genotypes. A significant difference was also found between the latter two groups
      (P= 0.034). In addition, the C(max) tended to be higher among subjects with the
      2677GG/3435CC genotype than those with the 2677GT/3435CT or 2677TT/3435TT
      genotypes (42.2 +/- 3.9 vs 32.2 +/- 16.2 vs 38.1 +/- 13.7 ng ml(-1)).
      CONCLUSIONS: Our study showed for the first time that verapamil pharmacokinetics
      may be influenced by particular genetic polymorphisms of the ABCB1 gene among
      healthy Chinese Han ethnic subjects. An individualized dosage regimen design
      incorporating such information may improve the efficacy of the drug whilst
      reducing adverse reactions.

PMID- 19740398
TI  - Aldosterone glucuronidation by human liver and kidney microsomes and recombinant
      UDP-glucuronosyltransferases: inhibition by NSAIDs.
AB  - AIMS: To characterize: i) the kinetics of aldosterone (ALDO) 18beta
      glucuronidation using human liver and human kidney microsomes and identify the
      human UGT enzyme(s) responsible for ALDO 18beta-glucuronidation and ii) the
      inhibition of ALDO 18beta-glucuronidation by non-selective NSAIDs. METHODS: Using
      HPLC and LC-MS methods, ALDO 18beta-glucuronidation was characterized using human
      liver (n= 6), human kidney microsomes (n= 5) and recombinant human UGT 1A1, 1A3,
      1A4, 1A5, 1A6, 1A7, 1A8, 1A9, 1A10, 2B4, 2B7, 2B10, 2B15, 2B17 and 2B28 as the
      enzyme sources. Inhibition of ALDO 18beta-glucuronidation was investigated using
      alclofenac, cicloprofen, diclofenac, diflunisal, fenoprofen, R- and S-ibuprofen,
      indomethacin, ketoprofen, ketorolac, meclofenamic acid, mefenamic acid, S
      naproxen, pirprofen and tiaprofenic acid. A rank order of inhibition (IC(50)) was
      established and the mechanism of inhibition investigated using diclofenac, S
      ibuprofen, indomethacin, mefenamic acid and S-naproxen. RESULTS: ALDO 18beta
      glucuronidation by hepatic and renal microsomes exhibited Michaelis-Menten
      kinetics. Mean (+/-SD) K(m), V(max) and CL(int) values for HLM and HKCM were 509
      +/- 137 and 367 +/- 170 microm, 1075 +/- 429 and 1110 +/- 522 pmol min(-1) mg(
      1), and 2.36 +/- 1.12 and 3.91 +/- 2.35 microl min(-1) mg(-1), respectively. Of
      the UGT proteins, only UGT1A10 and UGT2B7 converted ALDO to its 18beta
      glucuronide. All NSAIDs investigated inhibited ALDO 18beta-G formation by HLM,
      HKCM and UGT2B7. The rank order of inhibition (IC(50)) of renal and hepatic ALDO
      18beta-glucuronidation followed the general trend: fenamates > diclofenac >
      arylpropionates. CONCLUSION: A NSAID-ALDO interaction in vivo may result in
      elevated intra-renal concentrations of ALDO that may contribute to the adverse
      renal effects of NSAIDs and their effects on antihypertensive drug response.

PMID- 19740399
TI  - Influence of ABCB1 polymorphisms and haplotypes on tacrolimus nephrotoxicity and
      dosage requirements in children with liver transplant.
AB  - AIMS: The aim of this study was to investigate the influence of genetic
      polymorphisms in ABCB1 on the incidence of nephrotoxicity and tacrolimus dosage
      requirements in paediatric patients following liver transplantation. METHODS:
      Fifty-one paediatric liver transplant recipients receiving tacrolimus were
      genotyped for ABCB1 C1236>T, G2677>T and C3435>T polymorphisms. Dose-adjusted
      tacrolimus trough concentrations and estimated glomerular filtration rates (EGFR)
      indicative of renal toxicity were determined and correlated with the
      corresponding genotypes. RESULTS: The present study revealed a higher incidence
      of the ABCB1 variant-alleles examined among patients with renal dysfunction (> or
      =30% reduction in EGFR) at 6 months post-transplantation (1236T allele: 63.3% vs
      37.5% in controls, P= 0.019; 2677T allele: 63.3% vs. 35.9%, p = 0.012; 3435T
      allele: 60% vs. 39.1%, P= 0.057). Carriers of the G2677->T variant allele also
      had a significant reduction (%) in EGFR at 12 months post-transplant (mean
      difference = 22.6%; P= 0.031). Haplotype analysis showed a significant
      association between T-T-T haplotypes and an increased incidence of nephrotoxicity
      at 6 months post-transplantation (haplotype-frequency = 52.9% in nephrotoxic
      patients vs 29.4% in controls; P= 0.029). Furthermore, G2677->T and C3435->T
      polymorphisms and T-T-T haplotypes were significantly correlated with higher
      tacrolimus dose-adjusted pre-dose concentrations at various time points examined
      long after drug initiation. CONCLUSIONS: These findings suggest that ABCB1
      polymorphisms in the native intestine significantly influence tacrolimus dosage
      requirement in the stable phase after transplantation. In addition, ABCB1
      polymorphisms in paediatric liver transplant recipients may predispose them to
      nephrotoxicity over the first year post-transplantation. Genotyping future
      transplant recipients for ABCB1 polymorphisms, therefore, could have the
      potential to individualize better tacrolimus immunosuppressive therapy and
      enhance drug safety.

PMID- 19740400
TI  - Reporting rate of adverse drug reactions to the French pharmacovigilance system
      with three step 2 analgesic drugs: dextropropoxyphene, tramadol and codeine (in
      combination with paracetamol).
AB  - AIMS: Three 'weak' opioid analgesics in association with paracetamol are marketed
      in France as step 2 analgesics: dextropropoxyphene, tramadol and codeine. These
      combinations are involved in several adverse drug reactions (ADRs), but no data
      are available about their comparative reporting rate. The aim was to compare the
      reporting rate of ADRs between tramadol/paracetamol (TRM+P), codeine/paracetamol
      (COD+P) and dextropropoxyphene/paracetamol (DXP+P). METHODS: All spontaneous
      reports submitted to the French Pharmacovigilance Database from 1 January 1987 to
      31 December 2006 suspected to be induced by one of the three step 2 analgesic
      combinations (DXP+P, TRM+P, COD+P) were extracted. Their consumption for the same
      period was obtained from the French Drug Agency. The number of ADRs, serious ADRs
      and different organ classes of ADRs were compared according to their consumption.
      Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for
      each variable using DXP+P as reference. RESULTS: The reporting rate of ADRs was
      calculated as 24.9/100 000 person-years for DXP+P, 44.5/100 000 person-years for
      TRM+P and 12.5/100 000 person-years for COD+P. The reporting rate (OR 0.56, 95%
      CI 0.50, 0.63) and 'seriousness>>' (OR 0.65, 95% CI 0.53, 0.80) of ADRs were
      significantly higher with TRM+P than with DXP+P. However, hepatobiliary ADRs were
      significantly more frequent with the DXP+P combination (OR 2.62, 95% CI 1.59,
      4.37). In contrast, the reporting rate (OR 1.99, 95% CI 1.82, 2.18) and
      'seriousness' (OR 2.64, 95% CI 2.24, 3.11) of ADRs were significantly higher with
      DXP+P than with COD+P. CONCLUSIONS: Among the three step 2 analgesic
      combinations, reporting rate and 'seriousness' of ADRs are the highest with TRM+P
      and the lowest with COD+P. Our study suggests that the safety profile of DXP+P is
      worst than that of COD+P.

PMID- 19740401
TI  - Rhabdomyolysis a result of azithromycin and statins: an unrecognized interaction.
AB  - AIMS: In a systematic screening of the World Health Organization Adverse Drug
      Reaction database, VigiBase, in July 2008, a measure of association used to
      detect interactions (Omega) highlighted azithromycin with the individual statins
      atorvastatin, lovastatin and simvastatin and rhabdomyolysis. The aim was to
      examine all reports including rhabdomyolysis-azithromycin and statins in VigiBase
      to assess if the data were suggestive of an interaction. METHODS: The individual
      case reports in VigiBase and the original files were reviewed. In order to
      investigate the reporting over time for rhabdomyolysis with azithromycin and
      statins to VigiBase, Omega values were generated retrospectively. RESULTS: The
      reporting over time showed that rhabdomyolysis under concomitant use of
      azithromycin and statins was reported more often than expected from 2000 and
      onwards in Vigibase. After exclusion of possible duplicates and follow-up
      reports, 53 cases from five countries remained. Rhabdomyolysis occurred shortly
      after initiation of azithromycin in 23% of cases. In 11 patients an interaction
      had been suggested by the reporter. With the exception of one patient, the statin
      doses reported were within the recommended daily doses. CONCLUSIONS: Case reports
      in VigiBase are suggestive that interactions between azithromycin and statins
      resulting in rhabdomyolysis may occur. This analysis showed the potential of the
      newly developed disproportionality measure, Omega, which can help to identify
      drug interactions in VigiBase in the future. The results also showed that
      reviewing spontaneous reports can add information to drug interactions not
      established previously.

PMID- 19740402
TI  - Assessment of QT(c)-prolonging potential of BX471 in healthy volunteers. A
      'thorough QT study' following ICH E14 using various QT(c) correction methods.
AB  - AIMS: Within the framework of the clinical development of BX471, this study was
      intended to provide experience in conducting 'thorough QT(c) studies' according
      to ICH E14. A broad range of QT correction methods and analysis strategies was
      employed. METHODS A double-blind, placebo- and positive-controlled, single
      centre, three-way cross-over study was conducted in 74 healthy volunteers.
      Electrocardiograms were read by blinded experts. QT correction methods included
      Bazett's (QT(c)B), Fridericia's (QT(c)F) and several regression-based
      corrections. RESULTS: There was a significant QT(c)F prolongation of 10.26 ms by
      the positive control compared with placebo [95% confidence interval (7.83,
      12.70)]. BX471 at therapeutic doses did not cause substantial QT(c) prolongation
      [QT(c)F estimate 2.93 ms, 95% confidence interval (1.00, 4.86); QT(c)B estimate
      3.30 ms, 95% confidence interval (0.85, 5.74)]. Regression-based QT correction
      methods yielded similar results to Fridericia's correction [e.g. using a linear
      regression across the study population, QT(c) estimate 2.39 ms, 95% confidence
      interval (0.55, 4.23)]. Differences between the various regression-based
      correction methods were small. Results were not affected by whether the QT
      corrections were performed per ECG or per beat. CONCLUSIONS: BX471 does not cause
      meaningful QT(c) prolongation. Three QT correction methods may be sufficient in
      future studies: Bazett's (required by regulatory authorities), Fridericia's (as
      the most reliable fixed formula) and a regression-based correction (individually
      or population-based), each performed per ECG (i.e. applied to the means of
      several beats of one ECG recording).

PMID- 19740403
TI  - Population-based studies of antithyroid drugs and sudden cardiac death.
AB  - AIM: Thyroid free T4 is associated with QTc-interval prolongation, which is a
      risk factor for sudden cardiac death (SCD). Hyperthyroidism has been associated
      with SCD in case reports, but there are no population-based studies confirming
      this. The aim was to investigate whether use of antithyroid drugs (as a direct
      cause or as an indicator of poorly controlled hyperthyroidism) is associated with
      an increased risk of SCD. METHODS: We studied the occurrence of SCD in a two-step
      procedure in two different Dutch populations. First, the prospective population
      based Rotterdam Study including 7898 participants (> or =55 years old). Second,
      we used the Integrated Primary Care Information (IPCI) database, which is a
      longitudinal general practice research database to see whether we could replicate
      results from the first study. Drug use at the index date was assessed with
      prescription information from automated pharmacies (Rotterdam Study) or drug
      prescriptions from general practices (IPCI). We used a Cox proportional hazards
      model in a cohort analysis, adjusted for age, gender and use of QTc prolonging
      drugs (Rotterdam Study) and conditional logistic regression analysis in a case
      control analysis, matched for age, gender, practice and calendar time and
      adjusted for arrhythmia and cerebrovascular ischaemia (IPCI). RESULTS: In the
      Rotterdam Study, 375 participants developed SCD during follow-up. Current use of
      antithyroid drugs was associated with SCD [adjusted hazard ratio 3.9; 95%
      confidence interval (CI) 1.7, 8.7]. IPCI included 1424 cases with SCD and 14 443
      controls. Also in IPCI, current use of antithyroid drugs was associated with SCD
      (adjusted odds ratio 2.9; 95% CI 1.1, 7.4). CONCLUSIONS: Use of antithyroid drugs
      was associated with a threefold increased risk of SCD. Although this might be
      directly caused by antithyroid drug use, it might be more readily explained by
      underlying poorly controlled hyperthyroidism, since treated patients who
      developed SCD still had low thyroid-stimulating hormone levels shortly before
      death.

PMID- 19740404
TI  - Medication consumption in the Spanish paediatric population: related factors and
      time trend, 1993-2003.
AB  - AIMS: To ascertain the prevalence of consumption of medications in the Spanish
      paediatric population and to identify the factors associated with such
      consumption. METHODS: This was a descriptive, cross-sectional study covering the
      Spanish adult population, using data drawn from the 1993 and 2003 Spanish
      National Health Surveys (SNHS). The 1993 and 2003 SNHS include data on 5280 and
      6463 children, respectively, age range 0-15 years. The independent variables were
      sociodemographic and health-related, and the dependent variable was medications
      use. Using logistic multivariate regression models, we analysed the temporal
      evolution of medication consumption between 1993 and 2003. RESULTS: The 1993 SNHS
      data revealed that 36.81% of the paediatric population had consumed some type of
      medication, whereas in 2003 this figure had dropped to 34%. Over the decade of
      study, there was a significant decrease in use of medications for catarrh,
      influenza, throat (P < 0.05), and an increase in consumption of pain-relieving
      drugs and/or fever-lowering, antibiotics and anti-allergy remedies. Multivariate
      analysis highlighted the association between medication consumption, negative
      perception of the child's health [odds ratio (OR) 2.84, 95% confidence interval
      (CI) 2.16, 3.72 in 1993, and OR 3.54, 95% CI 2.74, 4.56 in 2003] and medical
      visits to the physician across the 2 years (OR 12.09, 95% CI 10.13, 14.42 in
      1993, and OR 7.17, 95% CI 6.06, 8.47 in 2003). CONCLUSIONS: Although there was a
      significant decline in overall drug consumption in the Spanish paediatric
      population from 1993 to 2003, the prevalence of consumption of certain groups,
      such as analgesics, antipyretics and antibiotics, has risen.

PMID- 19740405
TI  - Phenytoin-induced reduction of voriconazole serum concentration is not
      compensated by doubling the dosage.

PMID- 19740406
TI  - Three cases of severe hepatic impairment caused by erlotinib.

PMID- 19740407
TI  - Owen Lyndon Wade: clinical pharmacologist, 1921-2008.

PMID- 19740410
TI  - Adolescent-parent interactions and attitudes around screen time and sugary drink
      consumption: a qualitative study.
AB  - BACKGROUND: Little is known about how adolescents and their parents interact and
      talk about some of the key lifestyle behaviors that are associated with
      overweight and obesity, such as screen time (ST) and sugary drink (SD)
      consumption. This qualitative study aimed to explore adolescents' and parents'
      perceptions, attitudes, and interactions in regards to these topics. METHODS:
      Using an exploratory approach, semi-structured focus groups were conducted
      separately with adolescents and (unrelated) parents. Participants were recruited
      from low and middle socio-economic areas in the Sydney metropolitan area and a
      regional area of New South Wales, Australia. Transcripts were analysed using
      thematic analysis for each of the four content areas (adolescent-ST, adolescent
      SD consumption, parents' views on adolescents' ST and parents' views on
      adolescents' SD consumption). RESULTS: Nine focus groups, with a total of 63
      participants, were conducted. Broad themes spanned all groups: patterns of
      behavior; attitudes and concerns; adolescent-parent interactions; strategies for
      behavior change; and awareness of ST guidelines. While parents and adolescents
      described similar patterns of behaviour in relation to adolescents' SD
      consumption and ST, there were marked differences in their attitudes to these two
      behaviours which were also evident in the adolescent-parent interactions in the
      home that they described. Parents felt able to limit adolescents' access to SDs,
      but felt unable to control their adolescents' screen time. CONCLUSION: This study
      offers unique insights regarding topics rarely explored with parents or
      adolescents, yet which are part of everyday family life, are known to be linked
      to risk of weight gain, and are potentially amenable to change.

PMID- 19740409
TI  - CMR findings in patients with hypertrophic cardiomyopathy and atrial
      fibrillation.
AB  - OBJECTIVES: We sought to evaluate the relation between atrial fibrillation (AF)
      and the extent of myocardial scarring together with left ventricular (LV) and
      atrial parameters assessed by late gadolinium-enhancement (LGE) cardiovascular
      magnetic resonance (CMR) in patients with hypertrophic cardiomyopathy (HCM).
      BACKGROUND: AF is the most common arrhythmia in HCM. Myocardial scarring is also
      identified frequently in HCM. However, the impact of myocardial scarring assessed
      by LGE CMR on the presence of AF has not been evaluated yet. METHODS: 87 HCM
      patients underwent LGE CMR, echocardiography and regular ECG recordings. LV
      function, volumes, myocardial thickness, left atrial (LA) volume and the extent
      of LGE, were assessed using CMR and correlated to AF. Additionally, the presence
      of diastolic dysfunction and mitral regurgitation were obtained by
      echocardiography and also correlated to AF. RESULTS: Episodes of AF were
      documented in 37 patients (42%). Indexed LV volumes and mass were comparable
      between HCM patients with and without AF. However, indexed LA volume was
      significantly higher in HCM patients with AF than in HCM patients without AF (68
      +/- 24 ml.m-2 versus 46 +/- 18 ml.m-2, p = 0.0002, respectively). The mean extent
      of LGE was higher in HCM patients with AF than those without AF (12.4 +/- 14.5%
      versus 6.0 +/- 8.6%, p = 0.02). When adjusting for age, gender and LV mass, LGE
      and indexed LA volume significantly correlated to AF (r = 0.34, p = 0.02 and r =
      0.42, p < 0.001 respectively). By echocardiographic examination, LV diastolic
      dysfunction was evident in 35 (40%) patients. Mitral regurgitation greater than
      II was observed in 12 patients (14%). Multivariate analysis demonstrated that LA
      volume and presence of diastolic dysfunction were the only independent
      determinant of AF in HCM patients (p = 0.006, p = 0.01 respectively). Receiver
      operating characteristic curve analysis indicated good predictive performance of
      LA volume and LGE (AUC = 0.74 and 0.64 respectively) with respect to AF.
      CONCLUSION: HCM patients with AF display significantly more LGE than HCM patients
      without AF. However, the extent of LGE is inferior to the LA size for predicting
      AF prevalence. LA dilation is the strongest determinant of AF in HCM patients,
      and is related to the extent of LGE in the LV, irrespective of LV mass.

PMID- 19740411
TI  - FGFRL1 is a neglected putative actor of the FGF signalling pathway present in all
      major metazoan phyla.
AB  - BACKGROUND: Fibroblast Growth Factors (FGF) and their receptors are well known
      for having major implications in cell signalling controlling embryonic
      development. Recently, a gene coding for a protein closely related to FGFRs
      (Fibroblast Growth Factor Receptors) called FGFR5 or FGFR-like 1 (FGFRL1), has
      been described in vertebrates. An orthologous gene was also found in the
      cephalochordate amphioxus, but no orthologous genes were found by the authors in
      other non-vertebrate species, even if a FGFRL1 gene was identified in the sea
      urchin genome, as well as a closely related gene, named nou-darake, in the
      planarian Dugesia japonica. These intriguing data of a deuterostome-specific gene
      that might be implicated in FGF signalling prompted us to search for putative
      FGFRL1 orthologues in the completely sequenced genomes of metazoans. RESULTS: We
      found FGFRL1 genes in the cnidarian Nematostella vectensis as well as in many
      bilaterian species. Our analysis also shows that FGFRL1 orthologous genes are
      linked in the genome with other members of the FGF signalling pathway from
      cnidarians to bilaterians (distance < 10 Mb). To better understand the
      implication of FGFRL1 genes in chordate embryonic development, we have analyzed
      expression patterns of the amphioxus and the mouse genes by whole mount in situ
      hybridization. We show that some homologous expression territories can be
      defined, and we propose that FGFRL1 and FGF8/17/18 were already co-expressed in
      the pharyngeal endoderm in the ancestor of chordates. CONCLUSION: Our work sheds
      light on the existence of a putative FGF signalling pathway actor present in the
      ancestor of probably all metazoans, the function of which has received little
      attention until now.

PMID- 19740412
TI  - A comparative study of recombinant and native frutalin binding to human prostate
      tissues.
AB  - BACKGROUND: Numerous studies indicate that cancer cells present an aberrant
      glycosylation pattern that can be detected by lectin histochemistry. Lectins have
      shown the ability to recognise these modifications in several carcinomas, namely
      in the prostate carcinoma, one of the most lethal diseases in man. Thus, the aim
      of this work was to investigate if the alpha-D-galactose-binding plant lectin
      frutalin is able to detect such changes in the referred carcinoma. Frutalin was
      obtained from different sources namely, its natural source (plant origin) and a
      recombinant source (Pichia expression system). Finally, the results obtained with
      the two lectins were compared and their potential use as prostate tumour
      biomarkers was discussed. RESULTS: The binding of recombinant and native frutalin
      to specific glycoconjugates expressed in human prostate tissues was assessed by
      using an immuhistochemical technique. A total of 20 cases of prostate carcinoma
      and 25 cases of benign prostate hyperplasia were studied. Lectins bound directly
      to the tissues and anti-frutalin polyclonal antibody was used as the bridge to
      react with the complex biotinilated anti-rabbit IgG plus streptavidin-conjugated
      peroxidase. DAB was used as visual indicator to specifically localise the binding
      of the lectins to the tissues. Both lectins bound to the cells cytoplasm of the
      prostate carcinoma glands. The binding intensity of native frutalin was stronger
      in the neoplasic cells than in hyperplasic cells; however no significant
      statistical correlation could be found (P = 0.051). On the other hand,
      recombinant frutalin bound exclusively to the neoplasic cells and a significant
      positive statistical correlation was obtained (P < 0.00001). However, recombinant
      frutalin did not recognise all malignant prostate cases and, when positive, the
      binding to those tissues was heterogeneous. CONCLUSION: Native and recombinant
      frutalin yielded different binding responses in the prostate tissues due to their
      differences in carbohydrate-binding affinities. Also, this study shows that both
      lectins may be used as histochemical biomarkers for the prostate cancer.
      Moreover, the successful use of a recombinant lectin in immunohistochemical
      studies of prostate cancer was for the first time demonstrated, highlighting the
      advantages of using recombinant systems in the preparation of pure lectin samples
      for diagnostic purpose.

PMID- 19740413
TI  - Upper gastrointestinal symptoms, psychosocial co-morbidity and health care
      seeking in general practice: population based case control study.
AB  - BACKGROUND: The pathophysiology of upper gastrointestinal (GI) symptoms is still
      poorly understood. Psychological symptoms were found to be more common in
      patients with functional gastrointestinal complaints, but it is debated whether
      they are primarily linked to GI symptoms or rather represent motivations for
      health-care seeking. Purpose of our study was to compare co-morbidity, in
      particular psychological and social problems, between patients with and without
      upper GI symptoms. In addition, we investigated whether the prevalence of
      psychological and social problems is part of a broader pattern of illness related
      health care use. METHODS: Population based case control study based on the second
      Dutch National Survey of general practice (conducted in 2001). Cases (adults
      visiting their primary care physician (PCP) with upper GI symptoms) and controls
      (individuals not having any of these complaints), matched for gender, age, PCP
      practice and ethnicity were compared. Main outcome measures were contact
      frequency, prevalence of somatic as well as psychosocial diagnoses, prescription
      rate of (psycho)pharmacological agents, and referral rates. Data were analyzed
      using odds ratios, the Chi square test as well as multivariable logistic
      regression analysis. RESULTS: Data from 13,389 patients with upper GI symptoms
      and 13,389 control patients were analyzed. Patients with upper GI symptoms
      visited their PCP twice as frequently as controls (8.6 vs 4.4 times/year).
      Patients with upper GI symptoms presented not only more psychological and social
      problems, but also more other health problems to their PCP (odds ratios (ORs)
      ranging from 1.37 to 3.45). Patients with upper GI symptoms more frequently used
      drugs of any ATC-class (ORs ranging from 1.39 to 2.90), including psychotropic
      agents. The observed differences were less pronounced when we adjusted for non
      attending control patients. In multivariate regression analysis, contact
      frequency and not psychological or social co-morbidity was strongest associated
      with patients suffering from upper GI symptoms. CONCLUSION: Patients with upper
      GI symptoms visit their PCP more frequently for problems of any organ system,
      including psychosocial problems. The relationship between upper GI symptoms and
      psychological problems is equivocal and may reflect increased health care demands
      in general.

PMID- 19740414
TI  - Age-related delay in information accrual for faces: evidence from a parametric,
      single-trial EEG approach.
AB  - BACKGROUND: In this study, we quantified age-related changes in the time-course
      of face processing by means of an innovative single-trial ERP approach. Unlike
      analyses used in previous studies, our approach does not rely on peak
      measurements and can provide a more sensitive measure of processing delays. Young
      and old adults (mean ages 22 and 70 years) performed a non-speeded discrimination
      task between two faces. The phase spectrum of these faces was manipulated
      parametrically to create pictures that ranged between pure noise (0% phase
      information) and the undistorted signal (100% phase information), with five
      intermediate steps. RESULTS: Behavioural 75% correct thresholds were on average
      lower, and maximum accuracy was higher, in younger than older observers. ERPs
      from each subject were entered into a single-trial general linear regression
      model to identify variations in neural activity statistically associated with
      changes in image structure. The earliest age-related ERP differences occurred in
      the time window of the N170. Older observers had a significantly stronger N170 in
      response to noise, but this age difference decreased with increasing phase
      information. Overall, manipulating image phase information had a greater effect
      on ERPs from younger observers, which was quantified using a hierarchical
      modelling approach. Importantly, visual activity was modulated by the same
      stimulus parameters in younger and older subjects. The fit of the model, indexed
      by R2, was computed at multiple post-stimulus time points. The time-course of the
      R2 function showed a significantly slower processing in older observers starting
      around 120 ms after stimulus onset. This age-related delay increased over time to
      reach a maximum around 190 ms, at which latency younger observers had around 50
      ms time lead over older observers. CONCLUSION: Using a component-free ERP
      analysis that provides a precise timing of the visual system sensitivity to image
      structure, the current study demonstrates that older observers accumulate face
      information more slowly than younger subjects. Additionally, the N170 appears to
      be less face-sensitive in older observers.

PMID- 19740415
TI  - Genome-wide association reveals three SNPs associated with sporadic amyotrophic
      lateral sclerosis through a two-locus analysis.
AB  - BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal, degenerative
      neuromuscular disease characterized by a progressive loss of voluntary motor
      activity. About 95% of ALS patients are in "sporadic form"-meaning their disease
      is not associated with a family history of the disease. To date, the genetic
      factors of the sporadic form of ALS are poorly understood. METHODS: We proposed a
      two-stage approach based on seventeen biological plausible models to search for
      two-locus combinations that have significant joint effects to the disease in a
      genome-wide association study (GWAS). We used a two-stage strategy to reduce the
      computational burden associated with performing an exhaustive two-locus search
      across the genome. In the first stage, all SNPs were screened using a single
      marker test. In the second stage, all pairs made from the 1000 SNPs with the
      lowest p-values from the first stage were evaluated under each of the 17 two
      locus models. RESULTS: we performed the two-stage approach on a GWAS data set of
      sporadic ALS from the SNP Database at the NINDS Human Genetics Resource Center
      DNA and Cell Line Repository http://ccr.coriell.org/ninds/. Our two-locus
      analysis showed that two two-locus combinations--rs4363506 (SNP1) and rs3733242
      (SNP2), and rs4363506 and rs16984239 (SNP3) -- were significantly associated with
      sporadic ALS. After adjusting for multiple tests and multiple models, the
      combination of SNP1 and SNP2 had a p-value of 0.032 under the Dom intersection
      Dom epistatic model; SNP1 and SNP3 had a p-value of 0.042 under the Dom x Dom
      multiplicative model. CONCLUSION: The proposed two-stage analytical method can be
      used to search for joint effects of genes in GWAS. The two-stage strategy
      decreased the computational time and the multiple testing burdens associated with
      GWAS. We have also observed that the loci identified by our two-stage strategy
      can not be detected by single-locus tests.

PMID- 19740416
TI  - Finding one's way in proteomics: a protein species nomenclature.
AB  - Our knowledge of proteins has greatly improved in recent years, driven by new
      technologies in the fields of molecular biology and proteome research. It has
      become clear that from a single gene not only one single gene product but many
      different ones - termed protein species - are generated, all of which may be
      associated with different functions. Nonetheless, an unambiguous nomenclature for
      describing individual protein species is still lacking. With the present paper we
      therefore propose a systematic nomenclature for the comprehensive description of
      protein species. The protein species nomenclature is flexible and adaptable to
      every level of knowledge and of experimental data in accordance with the exact
      chemical composition of individual protein species. As a minimum description the
      entry name (gene name + species according to the UniProt knowledgebase) can be
      used, if no analytical data about the target protein species are available.

PMID- 19740417
TI  - Nebulized antithrombin limits bacterial outgrowth and lung injury in
      Streptococcus pneumoniae pneumonia in rats.
AB  - INTRODUCTION: Disturbed alveolar fibrin turnover is a cardinal feature of severe
      pneumonia. Clinical studies suggest that natural inhibitors of coagulation exert
      lung-protective effects via anticoagulant and possibly also anti-inflammatory
      pathways. Intravenous infusion of the natural anticoagulants increases the risk
      of bleeding. Local administration may allow for higher treatment dosages and
      increased local efficacy while at the same time reducing the risk of bleeding. We
      evaluated the effect of nebulized anticoagulants on pulmonary coagulopathy and
      inflammation in a rat model of Streptococcus pneumoniae pneumonia. METHODS: In
      this randomized controlled in vivo laboratory study rats were challenged
      intratracheally with S. pneumoniae, inducing pneumonia, and randomized to
      treatment with normal saline (placebo), recombinant human activated protein C (rh
      APC), plasma-derived antithrombin (AT), heparin or danaparoid, by means of
      nebulization. RESULTS: S. pneumoniae infection increased pulmonary levels of
      thrombin-antithrombin complexes and fibrin degradation products. All nebulized
      anticoagulants significantly limited pulmonary coagulopathy. None of the agents
      except danaparoid resulted in changes in systemic coagulopathy. Treatment with
      plasma-derived AT reduced outgrowth of S. pneumoniae and histopathologic damage
      in lungs. In vitro experiments confirmed outgrowth was reduced in bronchoalveolar
      lavage fluid (BALF) from rats treated with plasma-derived AT compared with
      placebo. Neutralizing of cationic components in BALF diminished the inhibitory
      effects on bacterial outgrowth of BALF, suggesting a role for cationic
      antimicrobial proteins. CONCLUSIONS: Nebulization of anticoagulants attenuates
      pulmonary coagulopathy during S. pneumoniae pneumonia in rats while only
      danaparoid affects systemic coagulation. Nebulized plasma-derived AT reduces
      bacterial outgrowth and exerts significant lung-protective effects.

PMID- 19740418
TI  - Efficacy and safety of tigecycline versus levofloxacin for community-acquired
      pneumonia.
AB  - BACKGROUND: Tigecycline, an expanded broad-spectrum glycylcycline, exhibits in
      vitro activity against many common pathogens associated with community-acquired
      pneumonia (CAP), as well as penetration into lung tissues that suggests
      effectiveness in hospitalized CAP patients. The aim of the present study was to
      compare the efficacy and safety of intravenous (IV) tigecycline with IV
      levofloxacin in hospitalized adults with CAP. METHODS: In this prospective,
      double-blind, non-inferiority phase 3 trial, eligible patients with a clinical
      diagnosis of CAP supported by radiographic evidence were stratified by Fine
      Pneumonia Severity Index and randomized to tigecycline or levofloxacin for 7-14
      days of therapy. Co-primary efficacy endpoints were clinical response in the
      clinically evaluable (CE) and clinical modified intent-to-treat (c-mITT)
      populations at test-of-cure (Day 10-21 post-therapy). RESULTS: Of the 428
      patients who received at least one dose of study drug, 79% had CAP of mild
      moderate severity according to their Fine score. Clinical cure rates for the CE
      population were 88.9% for tigecycline and 85.3% for levofloxacin. Corresponding c
      mITT population rates were 83.7% and 81.5%, respectively. Eradication rates for
      Streptococcus pneumoniae were 92% for tigecycline and 89% for levofloxacin.
      Nausea, vomiting, and diarrhoea were the most frequently reported adverse events.
      Rates of premature discontinuation of study drug or study withdrawal because of
      any adverse event were similar for both study drugs. CONCLUSION: These findings
      suggest that IV tigecycline is non-inferior to IV levofloxacin and is generally
      well-tolerated in the treatment of hospitalized adults with CAP. TRIAL
      REGISTRATION: NCT00081575.

PMID- 19740419
TI  - Risk factors for suicide in Bali: a psychological autopsy study.
AB  - BACKGROUND: The suicide rate in Bali has significantly increased in recent years.
      However, to date, there have been no case-control studies investigating risk
      factors for suicide. METHODS: A psychological autopsy study was conducted
      comparing 60 suicide cases and 120 living controls matched in age, sex, and area
      of residence. RESULTS: Multiple logistic regression analysis identified the
      following risk factors for suicide: at least one diagnosis of axis-I mental
      disorder (OR: 14.84 CI: 6.12 - 35.94); low level of religious involvement (OR:
      7.24 CI: 2.28 - 22.95); and severe interpersonal problems (OR: 3.86 CI: 1.36 -
      11.01). Forty-eight (80.0%) of the suicide cases were diagnosed with mental
      disorders; however, only 16.7% visited a primary care health professional and
      none received psychiatric treatment during the 1 month prior to death.
      CONCLUSION: Clinical, religious, and psychosocial factors were associated with
      suicide. These results highlight the significance of early recognition and
      treatment of mental disorders, religious activities, and interpersonal problem
      solving strategies for suicide prevention in Bali.

PMID- 19740420
TI  - Genetic determinants of mate recognition in Brachionus manjavacas (Rotifera).
AB  - BACKGROUND: Mate choice is of central importance to most animals, influencing
      population structure, speciation, and ultimately the survival of a species.
      Mating behavior of male brachionid rotifers is triggered by the product of a
      chemosensory gene, a glycoprotein on the body surface of females called the mate
      recognition pheromone. The mate recognition pheromone has been biochemically
      characterized, but little was known about the gene(s). We describe the isolation
      and characterization of the mate recognition pheromone gene through protein
      purification, N-terminal amino acid sequence determination, identification of the
      mate recognition pheromone gene from a cDNA library, sequencing, and RNAi
      knockdown to confirm the functional role of the mate recognition pheromone gene
      in rotifer mating. RESULTS: A 29 kD protein capable of eliciting rotifer male
      circling was isolated by high-performance liquid chromatography. Two transcript
      types containing the N-terminal sequence were identified in a cDNA library;
      further characterization by screening a genomic library and by polymerase chain
      reaction revealed two genes belonging to each type. Each gene begins with a
      signal peptide region followed by nearly perfect repeats of an 87 to 92 codon
      motif with no codons between repeats and the final motif prematurely terminated
      by the stop codon. The two Type A genes contain four and seven repeats and the
      two Type B genes contain three and five repeats, respectively. Only the Type B
      gene with three repeats encodes a peptide with a molecular weight of 29 kD. Each
      repeat of the Type B gene products contains three asparagines as potential sites
      for N-glycosylation; there are no asparagines in the Type A genes. RNAi with Type
      A double-stranded RNA did not result in less circling than in the phosphate
      buffered saline control, but transfection with Type B double-stranded RNA
      significantly reduced male circling by 17%. The very low divergence between
      repeat units, even at synonymous positions, suggests that the repeats are kept
      nearly identical through a process of concerted evolution. Information-rich
      molecules like surface glycoproteins are well adapted for chemical communication
      and aquatic animals may have evolved signaling systems based on these compounds,
      whereas insects use cuticular hydrocarbons. CONCLUSION: Owing to its critical
      role in mating, the mate recognition pheromone gene will be a useful molecular
      marker for exploring the mechanisms and rates of selection and the evolution of
      reproductive isolation and speciation using rotifers as a model system. The
      phylogenetic variation in the mate recognition pheromone gene can now be studied
      in conjunction with the large amount of ecological and population genetic data
      being gathered for the Brachionus plicatilis species complex to understand better
      the evolutionary drivers of cryptic speciation.

PMID- 19740421
TI  - Hepatitis B screening in the Turkish-Dutch population in Rotterdam, the
      Netherlands; qualitative assessment of socio-cultural determinants.
AB  - BACKGROUND: Hepatitis B is an important health problem in the Turkish community
      in the Netherlands. Increased voluntary screening is necessary in this community,
      to detect individuals eligible for treatment and to prevent further transmission
      of the disease. METHODS: We investigated socio-cultural determinants associated
      with hepatitis B screening in male and female, first and second generation
      Turkish migrants, by means of Focus Group Discussions. RESULTS: Socio-cultural
      themes related to hepatitis B screening were identified; these were social norm,
      social support, sensitivity regarding sexuality, reputation, responsiveness to
      authority, religious responsibility, cleanliness and religious doctrine regarding
      health and disease, and the perceived efficacy of Dutch health care services.
      Motivating factors were the (religious) responsibility for one's health, the
      perceived obligation when being invited for screening, and social support to get
      tested for hepatitis B. Perceived barriers were the association of hepatitis B
      screening with STDs or sexual activity, the perception of low control over one's
      health, and the perceived low efficacy of the Dutch health care services.
      Reputation could act as either a motivator or barrier. CONCLUSION: This study
      identified relevant socio-cultural themes related to hepatitis B screening, which
      may serve to customize interventions aimed at the promotion of voluntary
      hepatitis B screening in the Turkish-Dutch population in the Netherlands.

PMID- 19740422
TI  - Steroid Receptor RNA Activator Protein (SRAP): a potential new prognostic marker
      for estrogen receptor-positive/node-negative/younger breast cancer patients.
AB  - INTRODUCTION: The steroid receptor RNA activator is a functional RNA suspected to
      participate in the mechanisms underlying breast tumor progression. This RNA is
      also able to encode for a protein, Steroid Receptor RNA Activator Protein (SRAP),
      whose exact function remains to be determined. Our aim was to assess, in a large
      breast cancer cohort, whether levels of this protein could be associated with
      outcome or established clinical parameters. METHODS: Following antibody
      validation, SRAP expression was assessed by tissue-microarray (TMA) analysis of
      372 breast tumors. Clinical follow-up and parameters such as steroid receptor and
      node status were available for all the corresponding cases. Immunohistochemical
      scores were independently determined by three investigators and averaged.
      Statistical analyses were performed using standard univariate and multivariate
      tests. RESULTS: SRAP levels were significantly (Mann-Whitney rank sum test, P <
      0.05) higher in estrogen receptor-alpha positive (ER+, n = 271), in progesterone
      receptor positive (PR+, n = 257) and in older patients (age > 64 years, n = 182).
      When considering ER+ tumors, PR+ tumors, or younger patients (< or = 64 years),
      cases with high SRAP expression had a significantly (Mantel-Cox test, P < 0.05)
      worse breast cancer specific survival (BCSS) than those with low SRAP levels.
      SRAP also appeared as a very powerful indicator of poor prognostic for BCSS in
      the subset of ER+, node negative and young breast cancer patients (Cox regression
      analysis, n = 60, BCSS Hazard Ratio = 8.61, P < 0.006). CONCLUSIONS: Our data
      suggest that SRAP levels might provide additional information on potential risk
      of recurrence and negative outcome in a specific set of patients with otherwise
      good prognosis when considering only estrogen receptor and nodal status.

PMID- 19740423
TI  - Balloon kyphoplasty in malignant spinal fractures: a systematic review and meta
      analysis.
AB  - BACKGROUND: Spinal fractures are a common source of morbidity in cancer patients.
      Balloon Kyphoplasty (BKP) is a minimally invasive procedure designed to stabilize
      fractures and correct vertebral deformities. We performed a meta-analysis to
      determine the efficacy and safety of BKP for spinal fractures in cancer patients.
      METHODS: We searched several electronic databases up to September 2008 and the
      reference lists of relevant publications for studies reporting on BKP in patients
      with spinal fractures secondary to osteolytic metastasis and multiple myeloma.
      Outcomes sought included pain relief, functional capacity, quality of life,
      vertebral height, kyphotic angle and adverse events. Studies were assessed for
      methodological bias, and estimates of effect were calculated using a random
      effects model. Potential reasons for heterogeneity were explored. RESULTS: The
      literature search revealed seven relevant studies published from 2003 to 2008,
      none of which were randomized trials. Analysis of those studies indicated that
      BKP resulted in less pain and better functional outcomes, and that these effects
      were maintained up to 2 years post-procedure. While BKP also improved early
      vertebral height loss and spinal deformity, these effects were not long-term. No
      serious procedure-related complications were described. Clinically asymptomatic
      cement leakage occurred in 6% of all treated levels, and new vertebral fractures
      in 10% of patients. While there is a lack of studies comparing BKP to other
      interventions, some data suggested that BKP provided similar pain relief as
      vertebroplasty and a lower cement leakage rate. CONCLUSION: It appears that there
      is level III evidence showing BKP is a well-tolerated, relatively safe and
      effective technique that provides early pain relief and improved functional
      outcomes in patients with painful neoplastic spinal fractures. BKP also provided
      long-term benefits in terms of pain and disability. However, the methodological
      quality of the original studies prevents definitive conclusions being drawn.
      Further investigation into the use of BKP for spinal fractures in cancer patients
      is warranted.

PMID- 19740424
TI  - Fast optimization of statistical potentials for structurally constrained
      phylogenetic models.
AB  - BACKGROUND: Statistical approaches for protein design are relevant in the field
      of molecular evolutionary studies. In recent years, new, so-called structurally
      constrained (SC) models of protein-coding sequence evolution have been proposed,
      which use statistical potentials to assess sequence-structure compatibility. In a
      previous work, we defined a statistical framework for optimizing knowledge-based
      potentials especially suited to SC models. Our method used the maximum likelihood
      principle and provided what we call the joint potentials. However, the method
      required numerical estimations by the use of computationally heavy Markov Chain
      Monte Carlo sampling algorithms. RESULTS: Here, we develop an alternative
      optimization procedure, based on a leave-one-out argument coupled to fast
      gradient descent algorithms. We assess that the leave-one-out potential yields
      very similar results to the joint approach developed previously, both in terms of
      the resulting potential parameters, and by Bayes factor evaluation in a
      phylogenetic context. On the other hand, the leave-one-out approach results in a
      considerable computational benefit (up to a 1,000 fold decrease in computational
      time for the optimization procedure). CONCLUSION: Due to its computational speed,
      the optimization method we propose offers an attractive alternative for the
      design and empirical evaluation of alternative forms of potentials, using large
      data sets and high-dimensional parameterizations.

PMID- 19740425
TI  - The interventionalism of medicine: interventional radiology, cardiology, and
      neuroradiology.
AB  - Interventional medical practitioners are specialists who do minimally invasive
      procedures instead of surgery or other treatment. Most often, these procedures
      utilize various imaging and catheterization techniques in order to diagnose and
      treat vascular issues in the body. Interventionalist techniques, including
      injecting arteries with dye, visualizing these via x-ray, and opening up
      blockages, developed from early pioneers' bold and sometimes controversial
      experiments which aimed to find safer and better ways to treat coronary artery
      and other atherosclerotic vascular disease. Currently, the major interventional
      specialties are interventional (or vascular) radiology, interventional
      cardiology, and endovascular surgical (interventional) neuroradiology. All three
      are perfecting the use of stents and other procedures to keep diseased arteries
      open, while also evaluating the application these procedures. The rapid new
      development of imaging technologies, mechanical devices, and types of treatment,
      while certainly beneficial to the patient, can also lead to ambiguity regarding
      specific specialty claims on certain techniques and devices. While these
      practitioners can be in competition with each other, cooperation and
      communication are the most advantageous methods to deal with these "turf wars."
      All of the interventionalists are needed to deliver the best medical care to
      patients, now and in the future.

PMID- 19740426
TI  - VX-166: a novel potent small molecule caspase inhibitor as a potential therapy
      for sepsis.
AB  - INTRODUCTION: Prevention of lymphocyte apoptosis by caspase inhibition has been
      proposed as a novel treatment approach in sepsis. However, it has not been
      clearly demonstrated that caspase inhibitors improve survival in sepsis models
      when dosed post-insult. Also, there are concerns that caspase inhibitors might
      suppress the immune response. Here we characterize VX-166, a broad caspase
      inhibitor, as a novel potential treatment for sepsis. METHODS: VX-166 was studied
      in a number of enzymatic and cellular assays. The compound was then tested in a
      murine model of endotoxic shock (lipopolysaccharide (LPS), 20 mg/kg IV) and a 10
      d rat model of polymicrobial sepsis by caecal ligation and puncture (CLP).
      RESULTS: VX-166 showed potent anti-apoptotic activity in vitro and inhibited the
      release of interleukin (IL)-1beta and IL-18. In the LPS model, VX-166
      administered 0, 4, 8 and 12 h post-LPS significantly improved survival in a dose
      dependent fashion (P < 0.0028). In the CLP model, VX-166 continuously
      administered by mini-osmotic pump significantly improved survival when dosed 3 h
      after insult, (40% to 92%, P = 0.009). When dosed 8 h post-CLP, VX-166 improved
      survival from 40% to 66% (P = 0.19). Mode of action studies in the CLP model
      confirmed that VX-166 significantly inhibited thymic atrophy and lymphocyte
      apoptosis as determined by flow cytometry (P < 0.01). VX-166 reduced plasma
      endotoxin levels (P < 0.05), suggesting an improved clearance of bacteria from
      the bloodstream. Release of IL-1beta in vivo or T-cell activation in vitro were
      moderately affected. CONCLUSIONS: Our studies enhance the case for the use of
      caspase inhibitors in sepsis. VX-166 itself has promise as a therapy for the
      treatment of sepsis in man.

PMID- 19740427
TI  - Use of KikGR a photoconvertible green-to-red fluorescent protein for cell
      labeling and lineage analysis in ES cells and mouse embryos.
AB  - BACKGROUND: The use of genetically-encoded fluorescent proteins has
      revolutionized the fields of cell and developmental biology and in doing so
      redefined our understanding of the dynamic morphogenetic processes that shape the
      embryo. With the advent of more accessible and sophisticated imaging technologies
      as well as an abundance of fluorescent proteins with different spectral
      characteristics, the dynamic processes taking place in situ in living cells and
      tissues can now be probed. Photomodulatable fluorescent proteins are one of the
      emerging classes of genetically-encoded fluorescent proteins. RESULTS: We have
      compared PA-GFP, PS-CFP2, Kaede and KikGR four readily available and commonly
      used photomodulatable fluorescent proteins for use in ES cells and mice. Our
      results suggest that the green-to-red photoconvertible fluorescent protein,
      Kikume Green-Red (KikGR), is most suitable for cell labeling and lineage studies
      in ES cells and mice because it is developmentally neutral, bright and undergoes
      rapid and complete photoconversion. We have generated transgenic ES cell lines
      and strains of mice exhibiting robust widespread expression of KikGR. By
      efficient photoconversion of KikGR we labeled subpopulations of ES cells in
      culture, and groups of cells within ex utero cultured mouse embryos. Red
      fluorescent photoconverted cells and their progeny could be followed for extended
      periods of time. CONCLUSION: Transgenic ES cells and mice exhibiting widespread
      readily detectable expression of KikGR are indistinguishable from their wild type
      counterparts and are amenable to efficient photoconversion. They represent novel
      tools for non-invasive selective labeling specific cell populations and live
      imaging cell dynamics and cell fate. Genetically-encoded photomodulatable
      proteins such as KikGR represent emergent attractive alternatives to commonly
      used vital dyes, tissue grafts and genetic methods for investigating dynamic
      behaviors of individual cells, collective cell dynamics and fate mapping
      applications.

PMID- 19740428
TI  - Normal RNAi response in human fragile x fibroblasts.
AB  - BACKGROUND: Fragile x syndrome is caused by loss of expression of the FMRP
      protein involved in the control of a large number of mRNA targets. The Drosophila
      ortholog dFXR interacts with a protein complex that includes Argonaute2, an
      essential component of the RNA-induced silencing complex (RISC). Furthermore dFXR
      associates with Dicer, another essential processing enzyme of the RNAi pathway.
      Both microRNA and microRNA precursors can co-immunoprecipitate with dFXR.
      Consequently it has been suggested that the Fragile x syndrome may be due to a
      defect in an RNAi-related apparatus. FINDINGS: We have investigated the RNAi
      response in Fragile x patient cells lacking FMRP compared with normal controls.
      RNAi responses were successfully detected, but no statistically significant
      difference between the response in normal cells compared to patients cells was
      found - neither one nor two days after transfection. CONCLUSION: Our data show
      that in human fibroblasts from Fragile x patients lacking FMRP the RNAi response
      is not significantly impaired.

PMID- 19740429
TI  - RapidArc, intensity modulated photon and proton techniques for recurrent prostate
      cancer in previously irradiated patients: a treatment planning comparison study.
AB  - BACKGROUND: A study was performed comparing volumetric modulated arcs (RA) and
      intensity modulation (with photons, IMRT, or protons, IMPT) radiation therapy
      (RT) for patients with recurrent prostate cancer after RT. METHODS: Plans for RA,
      IMRT and IMPT were optimized for 7 patients. Prescribed dose was 56 Gy in 14
      fractions. The recurrent gross tumor volume (GTV) was defined on 18F
      fluorocholine PET/CT scans. Plans aimed to cover at least 95% of the planning
      target volume with a dose > 50.4 Gy. A maximum dose (DMax) of 61.6 Gy was allowed
      to 5% of the GTV. For the urethra, DMax was constrained to 37 Gy. Rectal DMedian
      was < 17 Gy. Results were analyzed using Dose-Volume Histogram and conformity
      index (CI90) parameters. RESULTS: Tumor coverage (GTV and PTV) was improved with
      RA (V95% 92.6 +/- 7.9 and 83.7 +/- 3.3%), when compared to IMRT (V95% 88.6 +/-
      10.8 and 77.2 +/- 2.2%). The corresponding values for IMPT were intermediate for
      the GTV (V95% 88.9 +/- 10.5%) and better for the PTV (V95%85.6 +/- 5.0%). The
      percentages of rectal and urethral volumes receiving intermediate doses (35 Gy)
      were significantly decreased with RA (5.1 +/- 3.0 and 38.0 +/- 25.3%) and IMPT
      (3.9 +/- 2.7 and 25.1 +/- 21.1%), when compared to IMRT (9.8 +/- 5.3 and 60.7 +/-
      41.7%). CI90 was 1.3 +/- 0.1 for photons and 1.6 +/- 0.2 for protons. Integral
      Dose was 1.1 +/- 0.5 Gy*cm3 *105 for IMPT and about a factor three higher for all
      photon's techniques. CONCLUSION: RA and IMPT showed improvements in conformal
      avoidance relative to fixed beam IMRT for 7 patients with recurrent prostate
      cancer. IMPT showed further sparing of organs at risk.

PMID- 19740431
TI  - Allele-specific expression assays using Solexa.
AB  - BACKGROUND: Allele-specific expression (ASE) assays can be used to identify cis,
      trans, and cis-by-trans regulatory variation. Understanding the source of
      expression variation has important implications for disease susceptibility,
      phenotypic diversity, and adaptation. While ASE is commonly measured via relative
      fluorescence at a SNP, next generation sequencing provides an opportunity to
      measure ASE in an accurate and high-throughput manner using read counts. RESULTS:
      We introduce a Solexa-based method to perform large numbers of ASE assays using
      only a single lane of a Solexa flowcell. In brief, transcripts of interest, which
      contain a known SNP, are PCR enriched and barcoded to enable multiplexing. Then
      high-throughput sequencing is used to estimate allele-specific expression using
      sequencing counts. To validate this method, we measured the allelic bias in a
      dilution series and found high correlations between measured and expected values
      (r>0.9, p < 0.001). We applied this method to a set of 5 genes in a Drosophila
      simulans parental mix, F1 and introgression and found that for these genes the
      majority of expression divergence can be explained by cis-regulatory variation.
      CONCLUSION: We present a new method with the capacity to measure ASE for large
      numbers of assays using as little as one lane of a Solexa flowcell. This will be
      a valuable technique for molecular and population genetic studies, as well as for
      verification of genome-wide data sets.

PMID- 19740430
TI  - A novel peptide (GX1) homing to gastric cancer vasculature inhibits angiogenesis
      and cooperates with TNF alpha in anti-tumor therapy.
AB  - BACKGROUND: The discovery of the importance of angiogenesis in tumor growth has
      emphasized the need to find specific vascular targets for tumor-targeted
      therapies. Previously, using phage display technology, we identified the peptide
      GX1 as having the ability to target the gastric cancer vasculature. The present
      study investigated the bioactivities of GX1, as well as its potential ability to
      cooperate with recombinant mutant human tumor necrosis factor alpha
      (rmhTNFalpha), in gastric cancer therapy. RESULTS: Tetrazolium salt (MTT) assay
      showed that GX1 could inhibit cell proliferation of both human umbilical vein
      endothelial cells (HUVEC) (44%) and HUVEC with tumor endothelium characteristics,
      generated by culturing in tumor-conditioned medium (co-HUVEC) (62%). Flow
      cytometry (FCM) and western blot assays showed that GX1 increased the rate of
      apoptosis from 11% to 31% (p < 0.01) by up-regulating caspase 3 expression level.
      A chorioallantoic membrane assay indicated that GX1 could suppress
      neovascularization in vivo, with the microvessel count decreasing from 21 to 11
      (p < 0.05). When GX1 was fused to rmhTNFalpha, GX1-rmhTNFalpha selectively
      concentrated in the gastric cancer vasculature, as shown by enzyme-linked
      immunosorbent assay, immunofluorescence and emission-computed tomography. In
      vitro MTT and FCM assays showed that, compared to rmhTNFalpha alone, GX1
      rmhTNFalpha was more effective at suppressing co-HUVEC proliferation (45% vs.
      61%, p < 0.05) and inducing apoptosis (11% vs. 23%, p < 0.05). In a tumor
      formation test, GX1-rmhTNFalpha more effectively inhibited tumor growth than
      rmhTNFalpha (tumor volume: 271 mm3 vs. 134 mm3, p < 0.05), with less systemic
      toxicity as measured by body weight (20.57 g vs. 19.30 g, p < 0.05). These
      therapeutic effects may be mediated by selectively enhanced tumor vascular
      permeability, as indicated by Evan's blue assay. CONCLUSION: GX1 had both homing
      activity and the ability to inhibit vascular endothelial cell proliferation in
      vitro and neovascularization in vivo. Furthermore, when GX1 was conjugated to
      rmhTNFalpha, the fusion protein was selectively delivered to targeted tumor
      sites, significantly improving the anti-tumor activity of rmhTNFalpha and
      decreasing systemic toxicity. These results demonstrate the potential of GX1 as a
      homing peptide in vascular targeted therapy for gastric cancer.

PMID- 19740432
TI  - Mining novel biomarkers for prognosis of gastric cancer with serum proteomics.
AB  - BACKGROUND: Although gastric cancer (GC) remains the second cause of cancer
      related death, useful biomarkers for prognosis are still unavailable. We present
      here the attempt of mining novel biomarkers for GC prognosis by using serum
      proteomics. METHODS: Sera from 43 GC patients and 41 controls with gastritis as
      Group 1 and 11 GC patients as Group 2 was successively detected by Surface
      Enhanced Laser Desorption/ionization Time of Flight Mass Spectrometry (SELDI-TOF
      MS) with Q10 chip. Peaks were acquired by Ciphergen ProteinChip Software 3.2.0
      and analyzed by Zhejiang University-ProteinChip Data Analysis System (ZJU-PDAS).
      CEA level were evaluated by chemiluminescence immunoassay. RESULTS: After median
      follow-up periods of 33 months, Group 1 with 4 GC patients lost was divided into
      20 good-prognosis GC patients (overall survival more than 24 months) and 19 poor
      prognosis GC patients (no more than 24 months). The established prognosis pattern
      consisted of 5 novel prognosis biomarkers with 84.2% sensitivity and 85.0%
      specificity, which were significantly higher than those of carcinoembryonic
      antigen (CEA) and TNM stage. We also tested prognosis pattern blindly in Group 2
      with 66.7% sensitivity and 80.0% specificity. Moreover, we found that 4474-Da
      peak elevated significantly in GC and was associated with advanced stage (III+IV)
      and short survival (p < 0.03). CONCLUSION: We have identified a number of novel
      biomarkers for prognosis prediction of GC by using SELDI-TOF-MS combined with
      sophisticated bioinformatics. Particularly, elevated expression of 4474-Da peak
      showed very promising to be developed into a novel biomarker associated with
      biologically aggressive features of GC.

PMID- 19740433
TI  - Therapeutic targeting of the focal adhesion complex prevents oncogenic TGF-beta
      signaling and metastasis.
AB  - INTRODUCTION: Mammary tumorigenesis is associated with the increased expression
      of several proteins in the focal adhesion complex, including focal adhesion
      kinase (FAK) and various integrins. Aberrant expression of these molecules occurs
      concomitant with the conversion of TGF-beta function from a tumor suppressor to a
      tumor promoter. We previously showed that interaction between beta3 integrin and
      TbetaR-II facilitates TGF-beta-mediated oncogenic signaling, epithelial
      mesenchymal transition (EMT), and metastasis. However, the molecular mechanisms
      by which the focal adhesion complex contributes to beta3 integrin:TbetaR-II
      signaling and the oncogenic conversion of TGF-beta remain poorly understood.
      METHODS: FAK expression and activity were inhibited in normal and malignant
      mammary epithelial cells (MECs) either genetically by using lentiviral-mediated
      delivery of shRNAs against FAK, or pharmacologically through in vitro and in vivo
      use of the FAK inhibitors, PF-562271 and PF-573228. Altered Smad2/3 and p38 MAPK
      activation, migration, EMT, and invasion in response to TGF-beta1 were monitored
      in FAK-manipulated cells. TbetaR-II expression was increased in metastatic breast
      cancer cells by retroviral transduction, and the metastasis of FAK- and TbetaR-II
      manipulated tumors was monitored by using bioluminescent imaging. RESULTS: TGF
      beta stimulation of MECs stabilized and activated FAK in a beta3 integrin- and
      Src-dependent manner. Furthermore, by using the human MCF10A breast cancer
      progression model, we showed that increased FAK expression in metastatic breast
      cancer cells mirrored the acquisition of enhanced activation of p38 MAPK by TGF
      beta. Administering FAK inhibitors or rendering metastatic breast cancer cells
      FAK deficient abrogated the interaction between beta3 integrin and TbetaR-II,
      thereby preventing TGF-beta from (a) activating p38 MAPK; (b) stimulating MEC
      invasion, migration, and EMT; and (c) inducing early primary tumor dissemination
      to the lungs. Finally, in contrast to FAK depletion, adjuvant FAK chemotherapy of
      mammary tumors decreased their growth in part by diminished macrophage tumor
      infiltration. CONCLUSIONS: Our studies identify an essential function for FAK in
      mediating the interaction between beta3 integrin and TbetaR-II, and thus in
      facilitating the oncogenic conversion of TGF-beta required for mammary tumor
      metastasis. Furthermore, this study establishes chemotherapeutic targeting of FAK
      as an effective, two-pronged approach in preventing tumor progression both by
      decreasing innate immune cell infiltration, and by inhibiting early TGF-beta
      dependent metastasis.

PMID- 19740434
TI  - Two adjacent nuclear factor-binding domains activate expression from the human
      PRNP promoter.
AB  - BACKGROUND: The transmissible spongiform encephalopathies (TSEs) comprise a group
      of fatal degenerative neurological diseases in humans and other mammals. After
      infection, the cellular prion protein isoform PrPC is converted to the
      pathological PrPSC scrapie isoform. The continued conversion of PrPC to PrPSC
      requires de novo endogenous PrP synthesis for disease progression. The human
      prion protein gene (PRNP) promoter was therefore investigated to identify
      regulatory elements that could serve as targets for therapeutic intervention.
      FINDINGS: The human prion protein gene (PRNP) promoter from position -1593 to
      +134 relative to the putative transcriptional start site (+1) was analyzed by
      transient transfection in HeLa cells. Deletions from the 5' end between positions
      -1593 and -232 yielded little change in activity. A further 5' deletion at
      position -90 resulted in a decline in activity to a level of about 30% of the
      full-length value. DNase I footprinting of the region between positions -259 and
      +2 identified two adjacent protected domains designated as prpA (-116 to -143)
      and prpB (-147 to -186). Internal deletions combined with mobility shift
      electrophoresis and methylation interference assays indicated the presence of
      sequence specific nuclear factor complexes that bind to the prpA and prpB domains
      and activate expression from the human PRNP promoter in an additive fashion.
      CONCLUSION: Results from transient transfection, DNase I footprinting, mobility
      shift electrophoresis, and methylation interference experiments suggest that two
      DNase I protected domains designated as prpA and prpB are binding sites for as
      yet unidentified regulatory factors that independently activate expression from
      the PRNP promoter.

PMID- 19740435
TI  - Genotype distribution of cervical human papillomavirus DNA in women with cervical
      lesions in Bioko, Equatorial Guinea.
AB  - BACKGROUND: The HVP vaccine is a useful tool for preventing cervical cancer. The
      purpose of this study is to determine the most frequent HPV genotypes in
      Equatorial Guinea in order to develop future vaccination strategies to apply in
      this country. METHODS: A campaign against cervical cancer was carried out in the
      area on a total of 1,680 women. 26 of the women, following cytological screening,
      were treated surgically with a loop electrosurgical excision procedure (LEEP).
      Cases were studied histologically and were genotyped from paraffin blocks by
      applying a commercial kit that recognized 35 HPV types. RESULTS: Cytological
      diagnoses included 17 HSIL, 1 LSIL, 5 ASC-H and 3 AGUS. Histological diagnosis
      resulted in 3 cases of microinvasive squamous cell carcinoma stage IA of FIGO, 9
      CIN-3, 8 CIN-2, 2 CIN-1, 3 flat condylomas and mild dysplasia of the endocervical
      epithelium. Fifteen of twenty-five cases genotyped were positive for HPV (60%).
      HPV 16 and 33 were identified in four cases each, HPV 58 in two other cases, and
      HPV 18, 31, 52, and 82 in one case, with one HPV 16 and 58 coinfection.
      CONCLUSION: The frequency of HPV types in the African area varies in comparison
      to other regions, particularly in Europe and USA. Vaccination against the five
      most common HPV types (16, 33, 58, 18, and 31) should be considered in the
      geographic region of West Africa and specifically in Equatorial Guinea.

PMID- 19740436
TI  - The attitude of Belgian social insurance physicians towards evidence-based
      practice and clinical practice guidelines.
AB  - BACKGROUND: Evidence-based medicine has broadened its scope and is starting to
      reach insurance medicine. Although still in its initial stages, physicians in the
      area of insurance medicine should keep up-to-date with the evidence on various
      diseases in order to correctly assess disability and to give appropriate advice
      about health care reimbursement. In order to explore future opportunities of
      evidence-based medicine to improve daily insurance medicine, there is a need for
      qualitative studies to better understand insurance physicians' perceptions of
      EBM. The present study was designed to identify the attitude of insurance
      physicians towards evidence-based medicine and clinical practice guidelines, and
      to determine their ability to access, retrieve and appraise the health evidence
      and the barriers for applying evidence to practice. METHODS: A cross-sectional
      survey study was carried out among all Dutch-speaking insurance physicians
      employed at one of the six Belgian social insurance sickness funds and at the
      National Institute of Disability and Health care Insurance (n = 224). Chi-square
      tests were used to compare nominal and ordinal variables. Student's t-tests,
      ANOVA, Mann-Whitney and Kruskal-Wallis were used to compare means of continuous
      variables for different groups. RESULTS: The response rate was 48.7%. The
      majority of respondents were positive towards evidence-based medicine and
      clinical practice guidelines. Their knowledge of EBM was rather poor. Perceived
      barriers for applying evidence to practice were mainly time and lack of EBM
      skills. CONCLUSION: Although the majority of physicians were positive towards EBM
      and welcomed more guidelines, the use of evidence and clinical practice
      guidelines in insurance medicine is low at present. It is in the first place
      important to eradicate the perceived inertia which limits the use of EBM and to
      further investigate the EBM principles in the context of insurance medicine.
      Available high-quality evidence-based resources (at the moment mainly originating
      from other medical fields) need to be structured in a way that is useful for
      insurance physicians and global access to this information needs to be ensured.

PMID- 19740437
TI  - "Just like fever": a qualitative study on the impact of antiretroviral provision
      on the normalisation of HIV in rural Tanzania and its implications for
      prevention.
AB  - BACKGROUND: Once effective therapy for a previously untreatable condition is made
      available, a normalisation of the disease often occurs. As part of a broader
      initiative to monitor the implementation of the national antiretroviral therapy
      (ART) programme, this qualitative study investigated the impact of ART
      availability on perceptions of HIV in a rural ward of North Tanzania and its
      implications for prevention. METHODS: A mix of qualitative methods was used
      including semi-structured interviews with 53 ART clinic clients and service
      providers. Four group activities were conducted with persons living with HIV.
      Data were analyzed using the qualitative software package NVIVO-7. RESULTS:
      People on ART often reported feeling increasingly comfortable with their status
      reflecting a certain "normalization" of the disease. This was attributed to
      seeing other people affected by HIV, regaining physical health, returning to
      productive activities and receiving emotional support from health service
      providers. Overcoming internalized feelings of shame facilitated disclosure of
      HIV status, helped to sustain treatment, and stimulated VCT uptake. However
      "blaming" stigma - where people living with HIV were considered responsible for
      acquiring a "moral disease" - persisted in the community and anticipating it was
      a key barrier to disclosure and VCT uptake. Attributing HIV symptoms to
      witchcraft seemed an effective mechanism to transfer "blame" from the family unit
      to an external force but could lead to treatment interruption. CONCLUSION: As
      long as an HIV diagnosis continues to have moral connotations, a de
      stigmatisation of HIV paralleling that occurring with diseases like cancer is
      unlikely to occur. Maximizing synergies between HIV treatment and prevention
      requires an enabling environment for HIV status disclosure, treatment
      continuation, and safer sexual behaviours. Local leaders should be informed and
      sensitised and communities mobilised to address the blame-dimension of HIV
      stigma.

PMID- 19740438
TI  - Differential expression of follistatin and FLRG in human breast proliferative
      disorders.
AB  - BACKGROUND: Activins are growth factors acting on cell growth and
      differentiation. Activins are expressed in high grade breast tumors and they
      display an antiproliferative effect inducing G0/G1 cell cycle arrest in breast
      cancer cell lines. Follistatin and follistatin- related gene (FLRG) bind and
      neutralize activins. In order to establish if these activin binding proteins are
      involved in breast tumor progression, the present study evaluated follistatin and
      FLRG pattern of mRNA and protein expression in normal human breast tissue and in
      different breast proliferative diseases. METHODS: Paraffin embedded specimens of
      normal breast (NB - n = 8); florid hyperplasia without atypia (FH - n = 17);
      fibroadenoma (FIB - n = 17); ductal carcinoma in situ (DCIS - n = 10) and
      infiltrating ductal carcinoma (IDC - n = 15) were processed for follistatin and
      FLRG immunohistochemistry and in situ hybridization. The area and intensity of
      chromogen epithelial and stromal staining were analyzed semi-quantitatively.
      RESULTS: Follistatin and FLRG were expressed both in normal tissue and in all the
      breast diseases investigated. Follistatin staining was detected in the epithelial
      cytoplasm and nucleus in normal, benign and malignant breast tissue, with a
      stronger staining intensity in the peri-alveolar stromal cells of FIB at both
      mRNA and protein levels. Conversely, FLRG area and intensity of mRNA and protein
      staining were higher both in the cytoplasm and in the nucleus of IDC epithelial
      cells when compared to NB, while no significant changes in the stromal intensity
      were observed in all the proliferative diseases analyzed. CONCLUSION: The present
      findings suggest a role for follistatin in breast benign disease, particularly in
      FIB, where its expression was increased in stromal cells. The up regulation of
      FLRG in IDC suggests a role for this protein in the progression of breast
      malignancy. As activin displays an anti-proliferative effect in human mammary
      cells, the present findings indicate that an increased FST and FLRG expression in
      breast proliferative diseases might counteract the anti-proliferative effects of
      activin in human breast cancer.

PMID- 19740439
TI  - RRW: repeated random walks on genome-scale protein networks for local cluster
      discovery.
AB  - BACKGROUND: We propose an efficient and biologically sensitive algorithm based on
      repeated random walks (RRW) for discovering functional modules, e.g., complexes
      and pathways, within large-scale protein networks. Compared to existing cluster
      identification techniques, RRW implicitly makes use of network topology, edge
      weights, and long range interactions between proteins. RESULTS: We apply the
      proposed technique on a functional network of yeast genes and accurately identify
      statistically significant clusters of proteins. We validate the biological
      significance of the results using known complexes in the MIPS complex catalogue
      database and well-characterized biological processes. We find that 90% of the
      created clusters have the majority of their catalogued proteins belonging to the
      same MIPS complex, and about 80% have the majority of their proteins involved in
      the same biological process. We compare our method to various other clustering
      techniques, such as the Markov Clustering Algorithm (MCL), and find a significant
      improvement in the RRW clusters' precision and accuracy values. CONCLUSION: RRW,
      which is a technique that exploits the topology of the network, is more precise
      and robust in finding local clusters. In addition, it has the added flexibility
      of being able to find multi-functional proteins by allowing overlapping clusters.

PMID- 19740440
TI  - Metabolism as means for hypoxia adaptation: metabolic profiling and flux balance
      analysis.
AB  - BACKGROUND: Cellular hypoxia is a component of many diseases, but mechanisms of
      global hypoxic adaptation and resistance are not completely understood.
      Previously, a population of Drosophila flies was experimentally selected over
      several generations to survive a chronically hypoxic environment. NMR-based
      metabolomics, combined with flux-balance simulations of genome-scale metabolic
      networks, can generate specific hypotheses for global reaction fluxes within the
      cell. We applied these techniques to compare metabolic activity during acute
      hypoxia in muscle tissue of adapted versus "naive" control flies. RESULTS:
      Metabolic profiles were gathered for adapted and control flies after exposure to
      acute hypoxia using 1H NMR spectroscopy. Principal Component Analysis suggested
      that the adapted flies are tuned to survive a specific oxygen level. Adapted
      flies better tolerate acute hypoxic stress, and we explored the mechanisms of
      this tolerance using a flux-balance model of central metabolism. In the model,
      adapted flies produced more ATP per glucose and created fewer protons than
      control flies, had lower pyruvate carboxylase flux, and had greater usage of
      Complex I over Complex II. CONCLUSION: We suggest a network-level hypothesis of
      metabolic regulation in hypoxia-adapted flies, in which lower baseline rates of
      biosynthesis in adapted flies draws less anaplerotic flux, resulting in lower
      rates of glycolysis, less acidosis, and more efficient use of substrate during
      acute hypoxic stress. In addition we suggest new specific hypothesis, which were
      found to be consistent with existing data.

PMID- 19740441
TI  - Myoepithelioma within the carpal tunnel: a case report and review of the
      literature.
AB  - Myoepitheliomas of the extremity are rare and usually benign, while a minority
      display malignant features. This case demonstrates the diagnosis and management
      of myoepithelioma within the carpal tunnel. Clinical and radiological tumour
      features were evaluated. Hematoxylin and eosin stained tumour sections were
      examined, and immunohistochemistry was performed. Histology revealed a nodular
      mass of epithelioid cells in clusters within a myxoid/chondroid stroma. No
      mitoses were noted. Cytokeratins, neuron-specific enolase, synaptophysin, glial
      fibrillary acidic protein, and S100 were positive on immunohistochemistry. A
      literature review revealed very few prior reports of myoepithelioma in the wrist,
      and limited data concerning any relationship between recurrence and quality of
      surgical margins. In this case, wide local excision would have significantly
      compromised dominant hand function, and therefore a marginal excision was deemed
      appropriate in the context of bland histological features. Surgical margins noted
      in future case reports will aid clinical decision making.

PMID- 19740442
TI  - Genetic diversity and evolution of human metapneumovirus fusion protein over
      twenty years.
AB  - BACKGROUND: Human metapneumovirus (HMPV) is an important cause of acute
      respiratory illness in children. We examined the diversity and molecular
      evolution of HMPV using 85 full-length F (fusion) gene sequences collected over a
      20-year period. RESULTS: The F gene sequences fell into two major groups, each
      with two subgroups, which exhibited a mean of 96% identity by predicted amino
      acid sequences. Amino acid identity within and between subgroups was higher than
      nucleotide identity, suggesting structural or functional constraints on F protein
      diversity. There was minimal progressive drift over time, and the genetic
      lineages were stable over the 20-year period. Several canonical amino acid
      differences discriminated between major subgroups, and polymorphic variations
      tended to cluster in discrete regions. The estimated rate of mutation was 7.12 x
      10(-4) substitutions/site/year and the estimated time to most recent common HMPV
      ancestor was 97 years (95% likelihood range 66-194 years). Analysis suggested
      that HMPV diverged from avian metapneumovirus type C (AMPV-C) 269 years ago (95%
      likelihood range 106-382 years). CONCLUSION: HMPV F protein remains conserved
      over decades. HMPV appears to have diverged from AMPV-C fairly recently.

PMID- 19740443
TI  - The Edinburgh Postnatal Depression Scale: translation and validation for a Greek
      sample.
AB  - BACKGROUND: Edinburgh Postnatal Depression Scale (EPDS) is an important screening
      instrument that is used routinely with mothers during the postpartum period for
      early identification of postnatal depression. The purpose of this study was to
      validate the Greek version of EPDS along with sensitivity, specificity and
      predictive values. METHODS: 120 mothers within 12 weeks postpartum were recruited
      from the perinatal care registers of the Maternity Departments of 4 Hospitals of
      Heraklion municipality, Greece. EPDS and Beck Depression Inventory-II (BDI-II)
      surveys were administered in random order to the mothers. Each mother was
      diagnosed with depression according to the validated Greek version of BDI-II. The
      psychometric measurements that were performed included: two independent samples t
      tests, One-way analysis of variance (ANOVA), reliability coefficients,
      Explanatory factor analysis using a Varimax rotation and Principal Components
      Method. Confirmatory analysis -known as structural equation modelling- of
      principal components was conducted by LISREL (Linear Structural Relations). A
      receiver operating characteristic (ROC) analysis was carried out to evaluate the
      global functioning of the scale. RESULTS: 8 (6.7%) of the mothers were diagnosed
      with major postnatal depression, 14 (11.7%) with moderate and 38 (31.7%) with
      mild depression on the basis of BDI-II scores. The internal consistency of the
      EPDS Greek version -using Chronbach's alpha coefficient- was found 0.804 and that
      of Guttman split-half coefficient 0.742. Our findings confirm the
      multidimensionality of EPDS, demonstrating a two-factor structure which contained
      subscales reflecting depressive symptoms and anxiety. The Confirmatory Factor
      analysis demonstrated that the two factor model offered a very good fit to our
      data. The area under ROC curve AUC was found 0.7470 and the logistic estimate for
      the threshold score of 8/9 fitted the model sensitivity at 76.7% and model
      specificity at 68.3%. CONCLUSION: Our data confirm the validity of the Greek
      version of the EPDS in identifying postnatal depression. The Greek EPDS scale
      could be used as a useful instrument in both clinical practice and research.

PMID- 19740444
TI  - Understanding and assessing the impact of treatment in diabetes: the Treatment
      Related Impact Measures for Diabetes and Devices (TRIM-Diabetes and TRIM-Diabetes
      Device).
AB  - PURPOSE: Diabetes is a debilitating illness requiring lifelong management.
      Treatments can be varied in terms of mode of administration as well as type of
      agent. Unfortunately, most patient reported outcome measures currently available
      to assess the impact of treatment are specific to diabetes type, treatment
      modality or delivery systems and are designed to be either a HRQoL or treatment
      satisfaction measure. To address these gaps, the Treatment Related Impact Measure
      Diabetes and Device measures were developed. This paper presents the item
      development and validation of the TRIM Diabetes/Device. METHODS: Patient
      interviews were conducted to collect the patient perspective and ensure high
      content validity. Interviews were hand coded and qualitatively analyzed to
      identify common themes. A conceptual model of the impact of diabetes medication
      was developed and preliminary items for the TRIM-Diabetes/Device were generated
      and cognitively debriefed. Validation data was collected via an on-line survey
      and analyzed according to an a priori statistical analysis plan to validate the
      overall score as well as each domain. Item level criteria were used to reduce the
      preliminary item pool. Next, factor analysis to identify structural domains was
      performed. Reliability and validity testing was then performed. RESULTS: One
      hundred and five patients were interviewed in focus groups, individual interviews
      and for cognitive debriefing. Five hundred seven patients participated in the
      validation study. Factor analysis identified seven domains: Treatment Burden,
      Daily Life; Diabetes Management; Psychological Health; Compliance and Device
      Function and Bother. Internal consistency reliability coefficients of the TRIM
      Diabetes/Device ranged from 0.80 and 0.94. Test-retest reliability of the TRIM
      Diabetes/Device ranged from 0.71 to 0.89. All convergent and known groups
      validity hypotheses were met for the TRIM-Diabetes/Device total scores and sub
      scales. CONCLUSION: Validation is an ongoing and iterative process. These
      findings are the first step in that process and have shown that both the TRIM
      Diabetes and the TRIM-Diabetes Device have acceptable psychometric properties.
      Future research is needed to continue the validation process and examine
      responsiveness and the validity of the TRIM-Diabetes/Device in a clinical trial
      population.

PMID- 19740445
TI  - As the bell tolls: a foundation study on pancreatic cancer consumer's research
      priorities.
AB  - BACKGROUND: This is the first investigation of its kind to explore the views of
      people affected by pancreatic cancer with regard to research priorities.
      Pancreatic cancer has an extremely poor outlook in terms of early diagnosis,
      effective treatment and survival. Those affected by the disease generally lack
      opportunities to voice their needs or concerns in an organised manner, link with
      others affected by the condition and take part in research. METHODS: This
      qualitative study adopts a self-selected telephone focussed discussion group
      approach. Information was obtained from distinct carer and patient groups after
      adequate controls such as the 'safe space' technique (repeatedly enquiring on and
      respecting the emotional needs) were implemented to protect participants from
      undue physical and psychological distress. RESULTS: Five themes emerged overall,
      with three themes being common between the patients and carers groups. Early
      detection, clinician communication and public awareness were areas of recurring
      discussion and consensus for both groups. The fourth theme to emerge for the
      patient group centred on quality of care, while the fourth theme of the carer
      group focused on the need for more and improved treatment options. CONCLUSION:
      Research priorities for pancreatic cancer consumers have been identified via an
      investigation that was tailored to meet exceptional needs. This research gives us
      a primary understanding of the role that pancreatic cancer patients can play in
      identifying areas of research that are responsive to their needs and priorities
      when suitably planned. Importantly it also provides a much greater understanding
      of the grim realities of the disease for those affected. This work is likely to
      be of value to anyone planning to work with those with a time limited,
      challenging condition.

PMID- 19740446
TI  - Homeostatic mechanisms in dopamine synthesis and release: a mathematical model.
AB  - BACKGROUND: Dopamine is a catecholamine that is used as a neurotransmitter both
      in the periphery and in the central nervous system. Dysfunction in various
      dopaminergic systems is known to be associated with various disorders, including
      schizophrenia, Parkinson's disease, and Tourette's syndrome. Furthermore,
      microdialysis studies have shown that addictive drugs increase extracellular
      dopamine and brain imaging has shown a correlation between euphoria and psycho
      stimulant-induced increases in extracellular dopamine 1. These consequences of
      dopamine dysfunction indicate the importance of maintaining dopamine
      functionality through homeostatic mechanisms that have been attributed to the
      delicate balance between synthesis, storage, release, metabolism, and reuptake.
      METHODS: We construct a mathematical model of dopamine synthesis, release, and
      reuptake and use it to study homeostasis in single dopaminergic neuron terminals.
      We investigate the substrate inhibition of tyrosine hydroxylase by tyrosine, the
      consequences of the rapid uptake of extracellular dopamine by the dopamine
      transporters, and the effects of the autoreceoptors on dopaminergic function. The
      main focus is to understand the regulation and control of synthesis and release
      and to explicate and interpret experimental findings. RESULTS: We show that the
      substrate inhibition of tyrosine hydroxylase by tyrosine stabilizes cytosolic and
      vesicular dopamine against changes in tyrosine availability due to meals. We find
      that the autoreceptors dampen the fluctuations in extracellular dopamine caused
      by changes in tyrosine hydroxylase expression and changes in the rate of firing.
      We show that short bursts of action potentials create significant dopamine
      signals against the background of tonic firing. We explain the observed time
      courses of extracellular dopamine responses to stimulation in wild type mice and
      mice that have genetically altered dopamine transporter densities and the
      observed half-lives of extracellular dopamine under various treatment protocols.
      CONCLUSION: Dopaminergic systems must respond robustly to important biological
      signals such as bursts, while at the same time maintaining homeostasis in the
      face of normal biological fluctuations in inputs, expression levels, and firing
      rates. This is accomplished through the cooperative effect of many different
      homeostatic mechanisms including special properties of tyrosine hydroxylase, the
      dopamine transporters, and the dopamine autoreceptors.

PMID- 19740447
TI  - Evolutionary conservation and changes in insect TRP channels.
AB  - BACKGROUND: TRP (Transient Receptor Potential) channels respond to diverse
      stimuli and thus function as the primary integrators of varied sensory
      information. They are also activated by various compounds and secondary
      messengers to mediate cell-cell interactions as well as to detect changes in the
      local environment. Their physiological roles have been primarily characterized
      only in mice and fruit flies, and evolutionary studies are limited. To understand
      the evolution of insect TRP channels and the mechanisms of integrating sensory
      inputs in insects, we have identified and compared TRP channel genes in
      Drosophila melanogaster, Bombyx mori, Tribolium castaneum, Apis mellifera,
      Nasonia vitripennis, and Pediculus humanus genomes as part of genome sequencing
      efforts. RESULTS: All the insects examined have 2 TRPV, 1 TRPN, 1 TRPM, 3 TRPC,
      and 1 TRPML subfamily members, demonstrating that these channels have the ancient
      origins in insects. The common pattern also suggests that the mechanisms for
      detecting mechanical and visual stimuli and maintaining lysosomal functions may
      be evolutionarily well conserved in insects. However, a TRPP channel, the most
      ancient TRP channel, is missing in B. mori, A. mellifera, and N. vitripennis.
      Although P. humanus and D. melanogaster contain 4 TRPA subfamily members, the
      other insects have 5 TRPA subfamily members. T. castaneum, A. mellifera, and N.
      vitripennis contain TRPA5 channels, which have been specifically retained or
      gained in Coleoptera and Hymenoptera. Furthermore, TRPA1, which functions for
      thermotaxis in Drosophila, is missing in A. mellifera and N. vitripennis;
      however, they have other Hymenoptera-specific TRPA channels (AmHsTRPA and
      NvHsTRPA). NvHsTRPA expressed in HEK293 cells is activated by temperature
      increase, demonstrating that HsTRPAs function as novel thermal sensors in
      Hymenoptera. CONCLUSION: The total number of insect TRP family members is 13-14,
      approximately half that of mammalian TRP family members. As shown for mammalian
      TRP channels, this may suggest that single TRP channels are responsible for
      integrating diverse sensory inputs to maintain the insect sensory systems. The
      above results demonstrate that there are both evolutionary conservation and
      changes in insect TRP channels. In particular, the evolutionary processes have
      been accelerated in the TRPA subfamily, indicating divergence in the mechanisms
      that insects use to detect environmental temperatures.

PMID- 19740448
TI  - Complications of Evans' syndrome in an infant with hereditary spherocytosis: a
      case report.
AB  - Hereditary spherocytosis (HS) is a genetic disorder of the red blood cell
      membrane clinically characterized by anemia, jaundice and splenomegaly. Evans'
      syndrome is a clinical syndrome characterized by autoimmune hemolytic anemia
      (AIHA) accompanied by immune thrombocytopenic purpura (ITP). It results from a
      malfunction of the immune system that produces multiple autoantibodies targeting
      at least red blood cells and platelets. HS and Evans' syndrome have different
      mechanisms of pathophysiology one another. We reported the quite rare case of an
      infant who had these diseases concurrently. Possible explanations of the
      unexpected complication are discussed.

PMID- 19740449
TI  - Diabetes related risk factors did not explain the increased risk for urinary
      incontinence among women with diabetes. The Norwegian HUNT/EPINCONT study.
AB  - BACKGROUND: Previous studies have shown an association between diabetes mellitus
      (DM) and urinary incontinence (UI) in women, especially severe UI. The purpose of
      this study was to investigate whether diabetes related variables could explain
      this association. METHODS: The study is part of the EPINCONT study, which is
      based on the large Nord-Trondelag Health Study 2 (HUNT 2), performed in the
      county of Nord-Trondelag, Norway, during the years 1995 - 1997. Questions on
      diabetes and UI were answered by a total of 21 057 women aged 20 years and older.
      Of these 685 were identified as having diabetes, and thus comprise the population
      of our study. A variety of clinical and biochemical variables were recorded from
      the participants. RESULTS: Blood-glucose, HbA1c, albumine:creatinine ratio (ACR),
      duration of diabetes, diabetes treatment, type of diabetes, cholesterol and
      triglycerides did not significantly differ in women with and without UI in crude
      analyses. However, the diabetic women with UI had more hospitalizations during
      the last 12 months, more homecare, and a higher prevalence of angina and use of
      oestrogene treatment (both local and oral/patch). After adjusting for age, BMI,
      parity and smoking, there were statistically significant associations between any
      UI and angina (OR 1.89; 95% CI: 1.22 - 2.93), homecare (OR 1.72; 95% CI: 1.02 -
      2.89), and hospitalization during the last 12 months (OR 1.67; 95% CI: 1.18 -
      2.38). In adjusted analyses severe UI was also significantly associated with the
      same variables, and also with diabetes drug treatment (OR 2.10; 95% CI: 1.07 -
      4.10) and stroke (OR 2.47; 95% CI: 1.09 - 5.59). CONCLUSION: No single diabetes
      related risk factor seems to explain the increased risk for UI among women with
      diabetes. However, we found associations between UI and some clinical correlates
      of diabetes.

PMID- 19740450
TI  - Efficacy and safety of infliximab induction therapy in Crohn's Disease in Central
      Europe--a Hungarian nationwide observational study.
AB  - BACKGROUND: Infliximab (IFX) has proven to be an effective addition to the
      therapeutic arsenal for refractory, fistulizing, and steroid dependent Crohn's
      disease (CD), with efficacy in the induction and maintenance of clinical
      remission of CD. Our objective in this study is to report the nationwide,
      multicenter experience with IFX induction therapy for CD in Hungary. METHODS:
      During a 6-year-period, beginning in 2000, a total of 363 CD patients were
      treated with IFX as induction therapy (5 mg/kg IFX infusions given at week 0, 2
      and 6) at eleven centers in Hungary in this observational study. Data analysis
      included patient demographics, important disease parameters and the outcome of
      IFX induction therapy. RESULTS: Three hundred and sixty three patients (183 women
      and 180 men) were treated with IFX since 2000. Mean age was 33.5 +/- 11.2 years
      and the mean duration of disease was 6.7 +/- 6.1 years. The population included
      114 patients (31.4%) with therapy-refractory CD, 195 patients (53.7%) with
      fistulas, 16 patients (4.4%) with both therapy-refractory CD and fistulas, and 26
      patients (7.2%) with steroid dependent CD. Overall response rate was 86.2%
      (313/363). A higher response rate was observed in patients with shorter disease
      duration (p = 0.05, OR:0.54, 95%CI:0.29-0.99) and concomitant immunosuppressant
      therapy (p = 0.05, OR: 2.03, 95%CI:0.165-0.596). Concomitant steroid treatment
      did not enhance the efficacy of IFX induction therapy. Adverse events included 34
      allergic reactions (9.4%), 17 delayed type hypersensitivity (4.7%), 16 infections
      (4.4%), and 3 malignancies (0.8%). CONCLUSION: IFX was safe and effective
      treatment in this cohort of Hungarian CD patients. Based on our experience co
      administration of immunosuppressant therapy is suggested in patients receiving
      IFX induction therapy. However, concomitant steroid treatment did not enhanced
      the efficacy of IFX induction therapy.

PMID- 19740451
TI  - CASSIOPE: an expert system for conserved regions searches.
AB  - BACKGROUND: Understanding genome evolution provides insight into biological
      mechanisms. For many years comparative genomics and analysis of conserved
      chromosomal regions have helped to unravel the mechanisms involved in genome
      evolution and their implications for the study of biological systems. Detection
      of conserved regions (descending from a common ancestor) not only helps clarify
      genome evolution but also makes it possible to identify quantitative trait loci
      (QTLs) and investigate gene function.The identification and comparison of
      conserved regions on a genome scale is computationally intensive, making process
      automation essential. Three key requirements are necessary: consideration of
      phylogeny to identify orthologs between multiple species, frequent updating of
      the annotation and panel of compared genomes and computation of statistical tests
      to assess the significance of identified conserved gene clusters. RESULTS: We
      developed a modular system superimposed on a multi-agent framework, called
      CASSIOPE (Clever Agent System for Synteny Inheritance and Other Phenomena in
      Evolution). CASSIOPE automatically identifies statistically significant conserved
      regions between multiple genomes based on automated phylogenies and statistical
      testing. Conserved regions were searched for in 19 species and 1,561 hits were
      found. To our knowledge, CASSIOPE is the first system to date that integrates
      evolutionary biology-based concepts and fulfills all three key requirements
      stated above. All results are available at
      http://194.57.197.245/cassiopeWeb/displayCluster?clusterId=1 CONCLUSION: CASSIOPE
      makes it possible to study conserved regions from a chosen query genetic region
      and to infer conserved gene clusters based on phylogenies and statistical tests
      assessing the significance of these conserved regions.Source code is freely
      available, please contact: Pierre.pontarotti@univ-provence.fr.

PMID- 19740452
TI  - Second-generation antipsychotics: a therapeutic downturn?

PMID- 19740453
TI  - Recurrent laryngeal nerve paralysis due to subclinical Lyme borreliosis.
AB  - OBJECTIVE: We report an extremely rare case of recurrent laryngeal nerve
      paralysis due to subclinical Lyme borreliosis. METHOD: Case report presenting a
      15-year-old girl referred with hoarseness and soft voice. RESULTS: Right-sided
      recurrent laryngeal nerve paralysis was observed using videolaryngoscopy. Imaging
      was used to exclude intracranial, cervical and intrathoracic embryological
      lesions, vascular malformations and tumours. Laboratory and electrophysiological
      investigations were used to exclude inflammatory and paraneoplastic processes,
      endocrinopathy and metabolic disorders. Serological testing was positive for Lyme
      disease. Parenteral ceftriaxone therapy was commenced. The patient's nerve
      paralysis showed complete recovery on the seventh day of antibiotic treatment;
      this was confirmed by videolaryngoscopy. CONCLUSION: Recurrent laryngeal nerve
      paralysis is an extremely rare complication of neuroborreliosis associated with
      Lyme disease. In patients with recurrent laryngeal nerve paralysis in whom the
      clinical history is uncertain and the usual diagnostic methods give negative
      results, screening with anti-borrelia immunoglobulin M is suggested.

PMID- 19740454
TI  - Vocal fold paralysis: role of bilateral transverse cordotomy.
AB  - OBJECTIVE: Although modern endoscopic laser techniques aim to avoid a permanent
      tracheostomy by augmenting the glottic aperture in cases of bilateral vocal fold
      palsy, loss of tissue from the posterior glottis risks compromising voice quality
      and swallowing function. The objective of this study was to describe our
      experience with bilateral transverse posterior cordotomy. METHODS: This was a
      retrospective analysis of functional outcomes in a series of consecutive patients
      undergoing a simple modification of the classical laser cordectomy procedure,
      which avoids tissue loss. The procedure was confined to the complete release of
      the vocal ligament from the arytenoid cartilage on both sides, while avoiding any
      significant loss of mucosa or cartilage. RESULTS: Post-operative voice quality
      and quality of life were rated as good by most patients, which makes bilateral
      transverse cordotomy an attractive treatment option for bilateral vocal fold
      paralysis. CONCLUSION: Bilateral transverse cordotomy is a reliable treatment
      option for patients with bilateral vocal fold paralysis, and aims to avoid the
      morbidity associated with a permanent tracheostomy.

PMID- 19740458
TI  - Family-with-sequence-similarity-46, member A (Fam46a) gene is expressed in
      developing tooth buds.
AB  - OBJECTIVE: In search for possible novel genes that may be involved in tooth
      development, we analysed the genome-wide transcriptome of developing mandibular
      tooth germs of mouse during embryonic and early life and selected family-with
      sequence-similarity-46, member A (Fam46a) gene for further expression analysis.
      METHODS: We applied microarray, quantitative real time polymerase chain reaction
      and in situ hybridisation methods for the expression study of the mouse Fam46a
      gene. RESULTS: We found the family-with-sequence-similarity-46, member A (Fam46a)
      gene to be highly expressed and further verify its temporo-spatial expression in
      the mouse tooth. CONCLUSION: We have shown that Fam46a is expressed in
      ameloblasts' nuclei of tooth germs and hypothesise that it might act together
      with morphogenetic factors important for the formation of enamel in mouse tooth.

PMID- 19740459
TI  - Structure of a novel highly branched alpha-glucan enzymatically produced from
      maltodextrin.
AB  - The bacterial strain PP710, isolated from soil and identified as Paenibacillus
      species, produced a low-digestibility alpha-glucan containing a large amylase
      resistant portion. This alpha-glucan was obtained in high yields from
      maltodextrin (dextrose equivalent 3) by using the condensed culture supernatant
      of the strain as the enzyme preparation. The water-soluble dietary fiber content
      of the low-digestibility alpha-glucan was 80.2%, and showed resistance to a rat
      intestinal enzyme preparation. The alpha-glucan was found to be a novel highly
      branched alpha-glucan by acid hydrolysis, NMR analysis, gel permeation
      chromatography, methylation analysis, and enzymatic digestion.

PMID- 19740460
TI  - [Indigenous amoebic hepatic abscess].

PMID- 19740461
TI  - Signalling signalhood and the emergence of communication.
AB  - A unique hallmark of human language is that it uses signals that are both learnt
      and symbolic. The emergence of such signals was therefore a defining event in
      human cognitive evolution, yet very little is known about how such a process
      occurs. Previous work provides some insights on how meaning can become attached
      to form, but a more foundational issue is presently unaddressed. How does a
      signal signal its own signalhood? That is, how do humans even know that
      communicative behaviour is indeed communicative in nature? We introduce an
      experimental game that has been designed to tackle this problem. We find that it
      is commonly resolved with a bootstrapping process, and that this process
      influences the final form of the communication system. Furthermore, sufficient
      common ground is observed to be integral to the recognition of signalhood, and
      the emergence of dialogue is observed to be the key step in the development of a
      system that can be employed to achieve shared goals.

PMID- 19740462
TI  - A cross-sectional analysis of type II diabetes in a community with exposure to
      perfluorooctanoic acid (PFOA).
AB  - BACKGROUND: Increased diabetes mortality has been reported in workers exposed to
      perfluorooctanoic acid (PFOA). We analyzed the relationships among serum PFOA,
      type II diabetes, and fasting glucose in a population with high levels of serum
      PFOA resulting from drinking contaminated water. METHODS: The study population
      was adults participating in a health survey in 2005-2006 (N=54,468). Subjects
      reported prevalent diabetes, age at diagnosis, and provided blood in which serum
      PFOA and glucose levels were measured. We conducted a case-control analysis
      restricted to long-time residents (> or =20 years, N=13,922), to maximize the
      likelihood that serum PFOA levels in 2005 reflected previous exposure. Cases
      (N=1055) were restricted to those with medical record validation and at least 10
      year residence prior to diagnosis. We also studied fasting glucose and serum PFOA
      in a subset (N=21,642). RESULTS: Median serum PFOA was 28 ng/ml, compared with 4
      ng/ml in the general US population. Reported diabetes prevalence was 7.8%,
      similar to what was expected. Adjusted for confounders, all upper deciles of
      serum PFOA had a decreased risk of diabetes compared with the lowest (odds ratios
      ORs by decile, 1.00, 0.71, 0.60, 0.72, 0.65, 0.65, 0.87, 0.58, 0.62, 0.72). There
      was no consistent pattern between fasting serum glucose and PFOA (glucose by
      decile, 94, 95, 95, 93, 94, 92, 92, 92, 92, 93, adjusted for confounders).
      CONCLUSIONS: Our findings do not demonstrate an association between PFOA and
      either type II diabetes or fasting glucose level. Our data are limited by their
      cross-sectional nature, and do not preclude the possibility of a causal
      relationship.

PMID- 19740463
TI  - Multivariate analysis of factors affecting probability of pregnancy and live
      birth with in vitro fertilization: an analysis of the Society for Assisted
      Reproductive Technology Clinic Outcomes Reporting System.
AB  - OBJECTIVE: To evaluate factors predictive of clinical pregnancy and of pregnancy
      loss from assisted reproductive technology (ART) using data from the Society for
      Assisted Reproductive Technology database for 2004-2006. DESIGN: Retrospective
      cohort. SETTING: Clinic-based data. PATIENT(S): The study population included
      225,889 fresh embryo transfer cycles using autologous oocytes and partner semen.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Clinical intrauterine gestation
      (presence of gestational sac) and live birth (>or=22 weeks gestation and >or=300
      g birth weight). RESULT(S): Increasing maternal age was significantly associated
      with a reduced odds of conception and increased fetal loss until 19 weeks
      gestation, but not with later pregnancy loss. Intracytoplasmic sperm injection
      (ICSI), assisted hatching, and increasing number of embryos transferred had
      significant positive effects on the odds of conception and pregnancy continuation
      through the first trimester, but did not affect the risk of later loss. Blacks,
      Asians, and Hispanics had significantly lower odds of clinical pregnancy compared
      with whites. Also compared with whites, Hispanics and Asians had a significantly
      greater risk of pregnancy loss in the second and third trimesters, and blacks had
      a significantly greater risk of pregnancy loss in all trimesters. CONCLUSION(S):
      Certain demographic and ART treatment parameters influenced chance of conception
      and early pregnancy loss, whereas black race and Hispanic ethnicity were also
      significantly associated with late pregnancy loss in ART-conceived pregnancies.

PMID- 19740464
TI  - Fixed intramedullary nailing and percutaneous autologous concentrated bone-marrow
      grafting can promote bone healing in humeral-shaft fractures with delayed union.
AB  - Treatment of humeral diaphyseal nonunion can be difficult and usually requires an
      extensive approach to the humerus with bone grafting, a procedure that could
      result in a lengthy operation with significant morbidity for the patient. The
      purpose of the present study is to describe a novel minimally invasive technique
      for the treatment of humeral-shaft fractures that do not demonstrate union
      progress within 16-24 weeks of injury. Fixed intramedullary nailing with
      percutaneously harvested and introduced autologous concentrated bone-marrow cells
      (mixed with demineralised bone matrix putty) was successfully used to treat five
      patients who had delayed union of a humeral-shaft fracture. The procedure was
      minimally invasive with no complications and resulted in sound union of all cases
      within 20 weeks.

PMID- 19740465
TI  - Effect of graft size on graft fracture rate after anterior lumbar spinal fusion
      in a sheep model.
AB  - STUDY DESIGN: Sheep anterior spinal fusion model with autogenous and xenogenous
      bone grafts. OBJECTIVE: To investigate whether the relationship between cross
      sectional area of the bone graft and area of the adjacent vertebral endplates has
      an effect on graft fracture rate. SUMMARY OF BACKGROUND DATA: Anterior
      spondylodesis with autogenous iliac crest transplant is a frequently performed
      operation to stabilize spinal motion segments but to date no precise
      recommendations with respect to minimum graft size are available in the
      literature. METHODS: Anterior spondylodesis using autogenous and xenogenous
      grafts of constant size in combination with an angular stable plate (Macs TL).
      Autogenous iliac crest graft was inserted in eight sheep and xenogenic,
      commercially available bovine graft (Tutobone) in the additional eight animals.
      The surface areas of the endplates of the fused intervertebral space were
      calculated using CT scans and contact radiographs of the specimens obtained after
      24 weeks. The graft itself was evaluated for fractures and osteolysis. RESULTS: A
      fracture occurred in tricortical, autogenous grafts if the graft cross-sectional
      area was less than 21% of the area of the adjacent endplates. All xenogenic
      grafts fractured and therefore a comparable value could not be determined.
      CONCLUSION: The results clearly indicate that the relation between graft cross
      sectional area and endplate area defines the survival or fracture of the graft in
      anterior spinal fusion. Although it is difficult to directly apply the results to
      the clinical situation it is suggested to choose a sufficiently large graft, in
      order to reduce the risk of autogenous graft fracture in anterior spondylodesis.

PMID- 19740466
TI  - Autologous stem cell therapy for peripheral arterial disease meta-analysis and
      systematic review of the literature.
AB  - BACKGROUND: Peripheral arterial disease (PAD) is a common cause of disability and
      mortality. Up to one third of patients are not susceptible to traditional
      revascularization and may benefit from stem cell therapies. OBJECTIVE: In this
      meta-analysis, we sought to determine whether autologous cell therapy is
      effective in the treatment of PAD. METHODS: We searched the English literature in
      Medline, Excerpta Medica and the Cochrane database for trials of autologous cell
      therapy in patients with PAD published before 31 January 2009. We included
      controlled and non-controlled, randomized and non-randomized trials using
      autologous bone marrow or granulocyte colony stimulating factor (G-CSF) mobilized
      peripheral blood cells to treat PAD. We also collected data from trials of G-CSF
      monotherapy, as a control treatment. RESULTS: In a meta-analysis of 37 trials,
      autologous cell therapy was effective in improving surrogate indexes of ischemia,
      subjective symptoms and hard endpoints (ulcer healing and amputation). On the
      contrary, G-CSF monotherapy was not associated with significant improvement in
      the same endpoints. Patients with thromboangiitis obliterans showed some larger
      benefits than patients with atherosclerotic PAD. The intramuscular route of
      administration and the use of bone marrow cells seemed somehow more effective
      than intrarterial administration and the use of mobilized peripheral blood cells.
      The procedures were well tolerated and generally safe. CONCLUSION: This meta
      analysis indicates that intramuscular autologous bone marrow cell therapy is a
      feasible, relatively safe and potentially effective therapeutic strategy for PAD
      patients, who are not candidate for traditional revascularization. Larger,
      placebo-controlled, randomized multicenter trials need to be planned and
      conducted to confirm these findings.

PMID- 19740467
TI  - Interactions among genetic variants from SREBP2 activating-related pathway on
      risk of coronary heart disease in Chinese Han population.
AB  - Sterol regulatory element binding proteins (SREBPs), as a family of membrane
      bound transcription factors, control the metabolism of cholesterol and fatty
      acids. We conducted a case-control study to investigate whether the common
      variants of genes from the SREBP2 activating-related pathway, involving SREBP2,
      SCAP, INSIG1 and INSIG2 genes, were associated with coronary heart disease (CHD)
      of Chinese Han population individually or interactively. Three, four and two
      single nucleotide polymorphisms (SNPs) from the INSIG1, INSIG2 and SCAP genes
      were chosen as haplotype-tagging SNPs (htSNPs), respectively, and one
      nonsynonymous coding SNP was selected from SREBP2. All of the SNPs were genotyped
      in 853 CHD cases and 948 unrelated control subjects. The interactions among SNPs
      of the four genes were evaluated with multifactor-dimensionality reduction (MDR)
      and logistic regression models (LRM). The results from MDR indicated that there
      existed the SNP-SNP interactive effect of INSIG1 gene on CHD (best prediction
      accuracy=56.09%, p=0.002 on 1000 permutations). The results from LRM also
      identified the 2-locus interaction model (adjusted p< or =0.001 for interaction)
      as well as the 3-locus gene-gene interaction (adjusted p=0.026 for interaction).
      Single polymorphism analysis showed that the rs4822063 of SREBP2 was associated
      with LDL-C in the controls. The genotype CC carriers had higher LDL-C than the
      major allele G carriers (3.44+/-0.90 mmol/L versus 3.17+/-0.84 mmol/L, adjusted
      p=0.038). Our results suggested that the INSIG1 gene was associated with CHD;
      there might be potential interactive effect on CHD among genes from SREBP2
      activating-related pathway; and the SREBP2 gene might be associated with plasma
      lipid level.

PMID- 19740468
TI  - Determination of phenolic compounds in modern and old varieties of durum wheat
      using liquid chromatography coupled with time-of-flight mass spectrometry.
AB  - An evaluation of the grain functional components of Italian durum wheat cultivars
      was conducted. The raw material was obtained from the field trial performed in
      2006-2007 at the Experimental Farm of the University of Bologna, (Bologna,
      Italy). The aim of this study was to define the phytochemical profile of ten
      varieties, comprised of old and modern durum wheat genotypes, including
      quantitative and qualitative phenolic and flavonoid content (free and bound
      forms). The results showed that mean values of total phenolic compound and total
      flavonoid content in old wheat varieties (878.2+/-19.0 micromol gallic acid
      equivalent/100g of grain and 122.6+/-25.4 micromol catechin equivalent/100g of
      grain, respectively) did not differ significantly from those detected in modern
      genotypes (865.9+/-128.9 micromol gallic acid equivalent/100g and 123.5+/-20.6
      micromol catechin equivalent/100g, respectively). However, the HPLC-ESI-TOF-MS
      analysis highlighted remarkable differences between modern and old cultivars. The
      interpretation of the mass spectra allowed the identification of 70 phenolic
      compounds, including coumarins, phenolic acids, anthocyanins, flavones,
      isoflavones, proanthocyanidins, stilbenes and lignans. The free extracts of
      ancient wheat varieties showed the presence of a mean number of phenolic
      compounds and isomer forms (8.7+/-2.5 and 7.7+/-4.7 respectively) significantly
      higher than in modern genotypes (4.4+/-2.9 and 2.0+/-2.4, respectively). A
      similar trend was observed also for the bound phenolic fraction. Moreover, the
      phytochemical profiles showed the presence of unique phenolic compounds in both
      free and bound fractions of some of the investigated wheat genotypes. Results
      highlighted that investigated old wheat cultivars may offer unique nutraceutical
      values for their peculiar contents in bioactive phytochemicals, suggesting their
      uses into a wide range of regular and specialty products naturally enriched with
      health-promoting compounds.

PMID- 19740469
TI  - Rapid optimization of dual-mode gradient high performance liquid chromatographic
      separation of Radix et Rhizoma Salviae Miltiorrhizae by response surface
      methodology.
AB  - An approach for rapid optimization of dual-mode gradient high performance liquid
      chromatography (HPLC) by response surface methodology (RSM) was developed for
      fast simultaneous separation of hydrophilic and hydrophobic components in Radix
      et Rhizoma Salviae Miltiorrhizae (Danshen) and its preparations. The aim of this
      study was to achieve a high throughput RSM optimization using a short ultra-high
      performance liquid chromatographic (UHPLC) column to simultaneously optimize flow
      rate and solvent gradient, and then transfer the optimized method to conventional
      HPLC for routine analytical purposes. The optimization was designed with Box
      Behnken design (BBD) and the global Derringer's desirability was used for
      describing the multicriteria response variables. Sixty-two designed experiments
      were performed by UHPLC with a short sub-2 microm column (2.1 mm x 50 mm, 1.7
      microm) and a total running time of only 5h. The predicted gradient profile was
      further transferred to a long UHPLC column (2.1 mm x 100 mm, 1.7 microm) and a
      conventional HPLC columns (2.1 mm x 100 mm, 3.5 microm and 4 mm x 100 mm, 5
      microm, respectively). Compared to the published methods, the newly developed
      dual-mode gradient is faster and more efficient at simultaneously separating
      hydrophilic and hydrophobic components in Danshen and its preparations.

PMID- 19740470
TI  - A new lipidomics approach by thin-layer chromatography-blot-matrix-assisted laser
      desorption/ionization imaging mass spectrometry for analyzing detailed patterns
      of phospholipid molecular species.
AB  - Thin-layer chromatography (TLC) is a highly established convenient technique for
      lipid separation and partial characterization of neutral and acidic
      glycosphingolipids (GSLs) and phospholipids, in mixtures. Meanwhile, imaging mass
      spectrometry (IMS) is a promising tool for lipidomics. However, some lipid
      classes are detected more sensitively than others, which can lead to suppression
      effects when complex mixtures are analyzed. Therefore to analyze complex lipid
      mixtures, a precise separation into the individual lipid classes is necessary.
      Here we present our highly sensitive and convenient analytical technology that
      combines TLC and IMS, namely the TLC-Blot-MALDI-IMS method, to visualize whole
      lipids and individual molecular species with high sensitivity compared with
      common staining methods. This method allows for easy visualization of all lipids
      with a linear range of approximately one order of magnitude and precision <16%
      RSD, making it useful for differential display analysis of lipids.

PMID- 19740471
TI  - A critical look at the definition of multidimensional separations.
AB  - Multidimensional (MD) separations, especially comprehensive two-dimensional (2D)
      separations such as comprehensive 2D LC (LCxLC), and comprehensive 2D GC (GCxGC),
      are potentially powerful separation techniques. It is important to have a clear
      definition of MD techniques to better understand the scope and boundaries of the
      subject. Widely accepted definitions of MD Separations have their roots in the
      definition proposed by Giddings. Giddings also added several comments that
      clarified the scope of his definition. However, some researchers extend Giddings'
      definitions beyond their intended scope. Doing so disqualifies such comprehensive
      2D techniques as LCxLC, GCxGC and 2D TLC from being considered as 2D techniques.
      In other instances, extended treatment of Giddings' definition is used as a basis
      to justify design-parameters of comprehensive 2D separations despite the fact
      that these parameters lead to sub-optimal implementations. We believe that the
      shortcomings in the definition and its popular interpretations are serious enough
      to warrant attention, especially by those interested in designing optimal
      instrumentation for MD separations like comprehensive 2D GC. After discussion of
      the weaknesses in the currently used definitions, we propose to define n
      dimensional analysis as one that generates n-dimensional displacement
      information. We believe that this definition captures the spirit of Giddings'
      definition while avoiding the problems associated with its popular
      interpretations.

PMID- 19740472
TI  - Characterisation of porous materials for bioseparation.
AB  - A set of chromatographic materials for bioseparation were characterised by
      various methods. Both commercial materials and new supports presenting various
      levels of rigidity were analysed. The methods included size-exclusion and
      capillary phenomena based techniques. Both batch exclusion and inverse size
      exclusion chromatography were used. Gas adsorption, mercury porosimetry and
      thermoporometry were applied as well as a new method based on water desorption
      starting from the saturated state. When the rigidity of adsorbents is high
      enough, the agreement is reasonable between the values of the structural
      parameters that were determined (surface area, porosity, and pore size) by
      various methods. Nevertheless, a part of macroporosity may not be evidenced by
      inverse size-exclusion chromatography whereas it is visible by batch exclusion
      and the other methods. When the rigidity decreases, for example with soft
      swelling gels, where standard nitrogen adsorption or mercury porosimetry are no
      more reliable, two main situations are encountered: either the methods based on
      capillary phenomena (thermoporometry or water desorption) overestimate the pore
      size with an amplitude that depends on the method, or in some cases it is
      possible to distinguish water involved in the swelling of pore walls from that
      involved in pore filling by capillary condensation.

PMID- 19740473
TI  - Pressurized liquid extraction of organophosphate triesters from sediment samples
      using aqueous solutions.
AB  - A novel procedure for the extraction of seven organophosphate triesters (OPs),
      used as flame retardants and plasticizers, from sediment samples has been
      developed. It is based on the pressurized liquid extraction of the analytes with
      aqueous solutions, combined with a further concentration step using solid-phase
      extraction (SPE) and followed by gas chromatography coupled to mass spectrometry
      (GC-MS) determination. The effects of different variables on the yield and
      selectivity of the sample preparation process are systematically evaluated. The
      optimal responses were observed extracting 2g of sediment with a
      water:acetonitrile (75:25) solution at 90 degrees C and 1500 psi for 5 min. The
      obtained extract was made up to 200 mL with ultrapure water and passed through an
      OASIS HLB, 60 mg cartridge. Analytes were recovered with 2 mL of ethyl acetate
      and this extract concentrated to a lower volume, ca. 0.2 mL. Recoveries of the
      proposed extraction method ranged from 77 to 111%, with relative standard
      deviations below 10%, for spiked river and marine sediment samples with total
      carbon contents (TC) up to 4.0%. The limits of quantification (LOQs) of the
      method varied between 0.5 and 5 ng g(-1). Analysis of non-spiked sediment samples
      revealed the presence of low levels for some of the investigated species, with
      the highest concentration (47 ng g(-1)) corresponding to tris(2-chloroethyl)
      phosphate (TCEP).

PMID- 19740474
TI  - Surface complexation modeling of Cd(II) adsorption on mixtures of hydrous ferric
      oxide, quartz and kaolinite.
AB  - Cadmium adsorption was measured as a function of ionic strength (0.001-0.1M
      NaNO(3)), and spanning a range of sorbate/sorbent ratios, on pure hydrous ferric
      oxide (HFO), kaolinite, and quartz and also on binary and ternary mixtures of the
      three solids. Diffuse- layer surface complexation models (DLMs) were
      parameterized to fit Cd sorption data for the pure kaolinite and quartz systems.
      Cd adsorption on kaolinite was modeled using a two-site DLM, with formation of a
      monodentate Cd complex on a variable charge site and Cd binding to a permanent
      exchange site; Cd adsorption on quartz was described using a one-site DLM with
      formation of a mondentate Cd complex on a variable charge site. These DLMs,
      together with the Dzombak and Morel DLM for HFO, were used to predict Cd
      adsorption on the binary and ternary mineral mixtures using a simple component
      additivity approach. In general, the predicted adsorption edges were in good
      agreement with measured data, with statistically similar goodness of fit compared
      to that obtained for the pure mineral systems. However, in some cases the model
      overpredicted Cd sorption, possibly indicating that interaction of the solids may
      prevent Cd from accessing all of the sorption sites.

PMID- 19740475
TI  - Chemisorption of methyl mercaptane on titania-supported Au nanoparticles:
      Viability of Au surface area determination.
AB  - Well-characterized Au nanoparticles were deposited on commercial TiO(2) (P25,
      Degussa) and analyzed by means of STEM and thermogravimetry coupled with mass
      spectrometry (TG-MS). The adsorption was studied on Au/TiO(2) samples with Au
      loadings in the range of 1.1-9.9wt.% by injecting pulses of CH(3)SH (methyl
      mercaptane, MM) until no further mass increase could be observed. A prerequisite
      for determination of the surface area of the deposited gold nanoparticles is the
      proper discrimination of species adsorbing on the Au nanoparticles and the
      titania support. The adsorption of methyl mercaptane on the titania support
      strongly depended on the pretreatment temperature (30-400 degrees C), whereas the
      adsorption on Au nanoparticles was virtually unaffected by this parameter. A very
      mild thermal pretreatment was identified as a requirement for avoiding the
      adsorption of the MM on the titania support. CH(3)SH adsorbed on the support
      desorbed at lower temperatures (maximal rate of desorption was centered at ca.
      150 degrees C) compared to species desorbing from Au nanoparticles (maximum at
      ca. 200-220 degrees C). Moreover, CH(3)SH adsorbed on Au nanoparticles desorbed
      in the form of dimethyl sulfide (CH(3))(2)S. Part of MM adsorbed on the gold
      surface was not desorbed even at high temperatures (above 500 degrees C) and
      stayed on the surface in the form of relatively stable C(x)H(y)S(z) fragments.
      This residue could be removed by oxygen pulses resulting in the formation of
      CO(2), SO(2), and H(2)O. The good discrimination of MM chemisorption on Au
      nanoparticles and on titania renders the determination of the Au surface area
      viable. Potential and limitations of the CH(3)SH chemisorption for the surface
      area determination of Au nanoparticles are discussed.

PMID- 19740476
TI  - Tailoring the surface potential of gold nanoparticles with self-assembled
      monolayers with mixed functional groups.
AB  - Self-assembled monolayer (SAM)-modified gold nanoparticles can be used to
      immobilize and transport molecules including DNA and proteins. However, these
      molecules are usually covalently bound to the surface and chemical reactions are
      required to cleave and release them. Therefore, immobilizing molecules using
      electrostatic interactions might be beneficial. In this work, Au nanoparticles
      modified by SAMs with mixed carboxylic acid and amine functional groups are
      presented. The surface potential and the iso-electric point (IEP) of the
      nanoparticles can be tailored by the ratio of these functional groups and
      arbitrary IEPs between 3.2 and 7.3 can be achieved. As a result, based on
      electrostatic interactions, molecules could be triggered to adsorb/desorb by
      changing the environmental pH around this tunable IEP. These engineered
      nanoparticles were synthesized in a single-phase system based on the reduction of
      HAuCl4 by NaBH4 in ethanol with a mixture of 16-mercaptohexadecanoic acid and 8
      amino-1-octanethiol that forms the SAM on the synthesized nanoparticles.
      Transmission electron microscopy, X-ray photoelectron spectroscopy, and
      electrophoresis light scattering revealed the particle size, ratio of the
      functional groups, and zeta-potential of the particles as a function of pH,
      respectively.

PMID- 19740477
TI  - Effect of the thermodynamic properties of W/O microemulsions on samarium oxide
      nanoparticle size.
AB  - In this work, we report the preparation of the Sm2O3 nanoparticle precursors
      (Sm(OH)3) via a simple W/O microemulsion process, in which microemulsions of
      cetyltrimethylammonium bromide (CTAB)/alkanol/1-octane/Sm(NO3)3 aqueous solution
      were added into sodium hydroxide (NaOH) aqueous solutions. The Sm2O3
      nanoparticles were then prepared by calcining the precursors at 900 degrees C.
      Particularly, DeltaG(c-->i), which is the change in standard Gibbs free energy
      for transferring cosurfactant from the continuous phase to the microemulsion
      interface and can be used to estimate the thermodynamic properties of
      microemulsions, was determined using the dilution method. The effects of alkanol
      carbon chain length (1-pentanol, 1-hexanol, 1-heptanol and 1-octanol) and the
      reaction temperatures (298, 308, 318 and 328 K) on both DeltaG(c-->i) and Sm2O3
      nanoparticle size have been investigated. Specifically, the Sm2O3 nanoparticle
      size, when calcined at 900 degrees C, was found to be mainly controlled by
      DeltaG(c-->i), and was thereby affected by the thermodynamic properties of
      microemulsions. The obtained products were characterized by DSC-TGA, XRD, TEM and
      UV-Vis. The results showed that DeltaG(c-->i) decreased with the increase in both
      the length of alkanol carbon chain and the reaction temperature, and the average
      size of Sm2O3 nanoparticles decreased as DeltaG(c-->i) decreased. The effect of
      microemulsion thermodynamic properties on Sm2O3 nanoparticle size reported here
      can provide some insights in controllable preparation of other rare earth oxide
      nanoparticles via the microemulsion route.

PMID- 19740478
TI  - Multiple thin film formation from dilute mixtures of polyethyleneimine (PEI) and
      cetyltrimethylammonium bromide (CTAB).
AB  - Dilute mixtures of the water soluble polymer polyethyleneimine (PEI) and the
      cationic surfactant cetyltrimethylammonium bromide (CTAB) form mesostructured
      thin films at the air/solution interface. In this paper we show that these films
      form spontaneously, reaching an equilibrium composition. When the film is
      removed, a new solid film rapidly reforms, with a similar morphology when
      inspected by Brewster angle microscopy (BAM). Successive removal of films lead to
      a series of structurally similar films, until the amount of surfactant in
      solution approaches the lower limit of film forming concentration. The results
      obtained using surfactant-selective potentiometry suggest that the incipient
      polymer:surfactant aggregates are in a position to migrate to the surface rapidly
      after film removal, prior to mesostructure formation. X-ray reflectivity
      indicates that films formed at different PEI:CTAB compositions retain mesophase
      regular structures with the same d-spacing feature, equal to 52.2A. Grazing
      incidence diffraction measurements indicate that films are composed of small
      crystallites arranged in a random powder fashion, developing a rough surface
      morphology evidenced by BAM. The central finding is that PEI:CTAB films form when
      the amount of CTAB in solution is higher than a critical film formation
      concentration, very close to the critical aggregation concentration (CAC),
      allowing the formation of several equilibrated films from the same growing
      solution.

PMID- 19740479
TI  - Systemic toxoplasmosis and concurrent porcine circovirus-2 infection in a pig.
AB  - Systemic toxoplasmosis and concurrent infection with porcine circovirus-2 (PCV-2)
      was diagnosed in a fattening pig. Clinical examination of the herd showed that up
      to 30% of the pigs of this weight group suffered from severe respiratory signs
      including sneezing and coughing, with a mortality rate of up to 5%. Gross
      necropsy examination revealed severe interstitial pneumonia and generalized
      lymphadenopathy. On microscopical examination there was necrotizing inflammation
      of the lung, adrenal glands and lymph nodes, associated with lymphoid depletion,
      cytoplasmic basophilic botryoid inclusion bodies and protozoal microorganisms.
      Infection with Toxoplasma gondii was confirmed by immunohistochemistry (IHC).
      Polymerase chain reaction analysis, in-situ hybridization and IHC confirmed
      systemic PCV-2 infection. These findings, associated with the respiratory signs
      and lesions in lymphoid tissues, are characteristic for post-weaning
      multisystemic wasting syndrome (PMWS). In this case, immunosuppression by PCV-2
      may have triggered systemic toxoplasmosis, or immune stimulation caused by
      coinfection with T. gondii may have caused extensive replication of PCV-2.

PMID- 19740480
TI  - Cutaneous angiomatosis in a llama (Lama glama).
AB  - Cutaneous angiomatosis was diagnosed in an adult female llama (Lama glama).
      Lesions were raised or plaque-like, erythematous, firm to soft in consistency and
      were observed on the face and skin of the axillary, abdominal, perineal and
      inguinal regions. The lesions were not painful or pruritic. Microscopical
      examination revealed an irregular parakeratotic lamellar hyperkeratosis
      associated with diffuse proliferation of arterioles and venules in the
      superficial dermis. Immunohistochemical analysis determined that the cells
      forming these vessels and perivascular cells expressed factor VIII-related
      antigen, vascular endothelial growth factor (VEGF), CD31 and smooth-muscle alpha
      actin. These studies confirmed the diagnosis of cutaneous angiomatosis.

PMID- 19740481
TI  - Reference values of electrocardiogram repolarization variables in a healthy
      population.
AB  - INTRODUCTION: Reference values for T-wave morphology analysis and evaluation of
      the relationship with age, sex, and heart rate are lacking in the literature. In
      this study, we characterized T-wave morphology in a large sample of healthy
      individuals. METHOD: A total of 1081 healthy subjects (83% men; range, 17-81
      years) were included. T-wave morphology variables describing the duration, area,
      slopes, amplitude, and distribution were calculated using 10-second digital
      electrocardiogram recordings. Multivariate regression was used to test for
      dependence of T-wave variables with the subject age, sex, and heart rate.
      RESULTS: Lead V5 (men vs women) T-wave variables were as follows: amplitude, 444
      versus 317 muV; area, 48.4 versus 33.2 ms mV; Tpeak-Tend interval, 94 versus 92
      milliseconds; maximal descending slope, -5.15 versus -3.69 muV/ms; skewness, 
      0.24 versus -0.22; and kurtosis, -0.36 versus -0.35. Tpeak-Tend interval,
      skewness, and kurtosis were independent of age, sex, and heart rate (r(2) <
      0.05), whereas Bazett-corrected QT-interval was more dependent (r(2) = 0.40).
      CONCLUSION: A selection of T-wave morphology variables is found to be clinically
      independent of age, sex, and heart rate, including Tpeak-Tend interval, skewness,
      and kurtosis.

PMID- 19740482
TI  - Interpretation of electrocardiograms by first-year residents: the need for
      change.
AB  - BACKGROUND: Prior studies have shown that misinterpretation of the
      electrocardiogram (ECG) can lead to inappropriate diagnoses and clinical
      decisions. This may be particularly true during the first month of postgraduate
      training. This study was designed to assess proficiency in ECG interpretation
      among residents at the start of their internal medicine (IM) residency. METHODS:
      Ten ECGs were selected from IM department teaching files. All were representative
      of conditions that a starting IM resident should be able to identify. The ECGs
      had 1 correct primary diagnosis and a short list of secondary findings as
      determined by 2 cardiologists who reviewed them independently. Fifty-two first
      year IM residents were given copies and asked to record their interpretations and
      an assessment of their certainty in each interpretation. Certainty was scored on
      a scale of 0 to 4 (0 representing a guess and 4 representing 100% certainty). Two
      blinded, independent graders scored each interpretation on a scale of 0 to 2 (0 =
      incorrect, 1 = partially correct, 2 = correct). RESULTS: Overall, only half of
      all ECGs were read correctly. For the most critical diagnoses, the mean scores
      were as follows: 1.73/2.0 for acute myocardial infarction, 1.5/2.0 for atrial
      flutter, 1.11/2.0 for ventricular tachycardia, and 0.23/2.0 for complete heart
      block. The average level of certainty recorded by all participants was low at
      18.5 of a maximum of 40. CONCLUSIONS: Internal medicine residents at the
      beginning of their residency training demonstrated low overall proficiency in
      interpreting ECGs and self-perceived confidence. Nearly all residents felt that
      their training was insufficient. These findings emphasize the need for improved
      and more effective training in ECG interpretation for physicians starting
      residency.

PMID- 19740483
TI  - The influence of negligence, intention, and outcome on children's moral
      judgments.
AB  - Piaget (1932) and subsequent researchers have reported that young children's
      moral judgments are based more on the outcomes of actions than on the agents'
      intentions. The current study investigated whether negligence might also
      influence these judgments and explain children's apparent focus on outcome.
      Children (3-8 years of age) and adults (N=139) rated accidental actions in which
      the valences of intention, negligence, and outcome were varied systematically.
      Participants of all ages were influenced primarily by intention, and well
      intentioned actions were also evaluated according to negligence and outcome. Only
      two young children based their judgments solely on outcome. It is suggested that
      previous studies have underestimated children's use of intention because outcome
      and negligence have been confounded. Negative consequences are considered to be
      important because children assume that they are caused by negligence. The
      findings indicate that young children can show sophisticated understanding of the
      roles of intention and negligence in moral judgments.

PMID- 19740484
TI  - Cardiovascular autonomic dysfunction in Parkinson's disease.
AB  - Symptoms of cardiovascular dysautonomia are a common occurrence in Parkinson's
      disease (PD). In addition to this dysautonomia as part of PD itself, dysfunction
      of the autonomic nervous system (ANS) can be triggered as a side-effect of drug
      treatment interacting with the ANS or - if prominent and early - an indication of
      a different disease such as multiple system atrophy (MSA). Various diagnostic
      tests are available to demonstrate autonomic failure. While autonomic function
      tests can differentiate parasympathetic from sympathetic dysfunction, cardiac
      imaging can define the pathophysiologically involved site of a lesion. Standard
      tests such as 24-h ambulatory blood pressure measurements can identify
      significant autonomic failure which needs treatment. The most frequent and
      disturbing symptom of cardiovascular autonomic dysfunction is orthostatic
      hypotension. Symptoms include generalized weakness, light-headiness, mental
      "clouding" up to syncope. Factors like heat, food, alcohol, exercise, activities
      which increase intrathoraric pressure (e.g. defecation, coughing) and certain
      drugs (e.g. vasodilators) can worsen a probably asymptomatic orthostatic
      hypotension. Non-medical and medical therapies can help the patient to cope with
      a disabling symptomatic orthostatic hypotension. Supine hypertension is often
      associated with orthostatic hypotension. The prognostic role of cardiovagal and
      baroreflex dysfunction is still not yet known.

PMID- 19740485
TI  - Neuromyelitis optica: effect of gender.
AB  - Neuromyelitis optica is a distinct CNS demyelinating disease associated with the
      autoantibody NMO-IgG, which targets the water channel aquaporin-4. Neuromyelitis
      optica may be distinguished from typical multiple sclerosis on the basis of key
      clinical and neuroimaging characteristics in addition to detection of NMO-IgG.
      The disease has an even stronger female predilection than does multiple
      sclerosis, with a reasonably consistent female to male gender ratio of >3:1
      reported from samples of diverse racial and regional populations worldwide. The
      gender distribution appears to be similar in both childhood-onset and adult-onset
      cases. Female gender is associated with a relapsing course and familial disease,
      but the influence of gender on disease severity and treatment response are not
      clear. Population-based epidemiological and genetic studies, with case
      ascertainment aided by the high specificity of NMO-IgG and consistent disease
      definitions, are needed to better define and understand gender effects in
      neuromyelitis optica.

PMID- 19740486
TI  - Epidemiology of psychosis in Parkinson's disease.
AB  - Psychotic symptoms are frequent and disabling in patients with Parkinson's
      disease (PD). Methodological issues in the epidemiology of PD associated
      psychosis (PDP) include differences in the symptoms assessed, the methods of
      assessment, and the selection of patients. Most studies are prospective clinic
      based cross-sectional studies providing point prevalence rates in samples on
      dopaminergic treatment. Visual hallucinations are present in about one quarter to
      one third of the patients, auditory in up to 20%. Tactile/somatic, and olfactory
      hallucinations are usually not systematically sought. Minor phenomena such as
      sense of presence and visual illusions affect 17 to 72% of the patients, and
      delusions about 5%. Lifetime prevalence of visual hallucinations reaches
      approximately 50%. Prospective longitudinal cohort studies suggest that
      hallucinations persist and worsen in individual patients, and that their
      prevalence increases with time. A facilitating role of treatment on PDP is
      demonstrated at least for dopaminergic agonists, but there is no simple dose
      effect relationship between dopaminergic treatment and the presence or severity
      of hallucinations. The main endogenous non-modifiable risk factor is cognitive
      impairment. Other associated factors include older age/longer duration of PD,
      disease severity, altered dream phenomena, daytime somnolence, and possibly
      depression and dysautonomia. PDP reduces quality of life in patients and
      increases caregiver distress, and is an independent risk factor for nursing home
      placement and development of dementia.

PMID- 19740487
TI  - Predisposing factors for acute deterioration of minor ischemic stroke.
AB  - PURPOSE: Since attention should be paid to acute stroke patients who may easily
      worsen, we investigated the predisposing factors for acute deterioration of minor
      ischemic stroke in Japanese patients. METHODS: We retrospectively investigated
      543 patients who were admitted within 7 days of the occurrence of an acute minor
      stroke with National Institute of Health Stroke Scale (NIHSS) score of 4 or less,
      between January 2002 and September 2005. Deterioration of neurological findings
      was defined as the worsening by 2 points or more of the NIHSS score during
      admission to the hospital. RESULTS: Out of 543 patients, deterioration was noted
      in 37 patients (6.8%: deterioration group), and not in the other 506 patients
      (93.2%: non-deterioration group). Multivariate analysis demonstrated that the
      factors associated with worsening were atherothrombotic brain infarction
      (deterioration group vs. non-deterioration group: 35.1% vs. 18.0%, P=0.049),
      elevated systolic blood pressure (170.5+/-32.4 mm Hg vs. 160.4+/-27.4 mm Hg,
      P=0.033), serum glucose level on admission (146.1+/-60.5mg/dL vs. 121.7+/-54.9
      mg/dL, P=0.048), and presence of paralysis (73.0% vs. 54.9%, P=0.003) and vertigo
      (16.2% vs. 7.9%, P=0.034). The more factors there were that were associated with
      worsening (atherothrombotic infarction; systolic blood pressure >140 mm Hg; serum
      glucose level >140 mg/dL; and paralysis, vertigo, and dizziness), the more
      frequently the deterioration occurred (number of worsening factors 0-2: 4.6%, 3:
      12.8%, 4: 32.3%). Although over 80% of patients in the group without
      deterioration had good functional outcome at discharge, over 90% of patients with
      deterioration either were discharged to nursing home care or died. CONCLUSION: In
      this study, the predisposing factors for acute deterioration in minor ischemic
      stroke were atherothrombotic brain infarction; high blood pressure; elevated
      serum glucose level; and paralysis, vertigo, and dizziness. Once patients with
      minor ischemic stroke deteriorated, their functional outcome at discharge was
      significantly worse than those who had not deteriorated.

PMID- 19740488
TI  - Are genetic and sporadic Parkinson's disease patients equally susceptible to
      develop dementia?
AB  - The occurrence of dementia in genetic Parkinson's disease is heterogeneous. The
      onset and progression of diverse forms of familial Parkinson's disease might be
      different than that of sporadic disease. Since dementia is an age related
      process, its risk increases with advanced disease severity and duration. The
      onset and progression of dementia is expected to vary between genetic forms,
      which present at diverse ages with different symptomatologies. It seems that
      genetic Parkinson's disease variants in which Lewy bodies are the prominent
      pathological hallmark - such as in PARK1, PARK4 and PARK8 - dementia is part of
      the phenotype. On the contrary, in PARK2 which is not accompanied by Lewy body
      accumulation, patients do not show a systematic cognitive decline. This review
      presents information on dementia in genetic forms of Parkinson's disease.

PMID- 19740489
TI  - Long-term outcome of modified maze procedure combined with mitral valve surgery:
      analysis of outcomes according to type of mitral valve surgery.
AB  - OBJECTIVE: Efficacy of the maze procedure for atrial fibrillation associated with
      advanced mitral disease not amenable to repair has not been determined. This
      study investigated whether type of mitral surgery affects maze outcome. METHODS:
      From January 1999 to January 2007, a total of 435 patients underwent the maze
      procedure and concomitant mitral operation. Of these, 226 underwent mitral repair
      and 209 underwent mitral replacement. RESULTS: Median follow-up was 40.6 months
      (0.4-111.3 months), with 25 deaths and 6 strokes. Nineteen patients did not
      regain normal sinus rhythm. There were no significant intergroup differences in
      survival, stroke incidence, or sinus rhythm restoration rate. Among 427 early
      survivors, 64 had late atrial fibrillation recurrence. Five-year atrial
      fibrillation-free rates were 80.9% + or - 3.7% in the repair group and 77.3% + or
      - 4.1% in the replacement group (P = .099). By multivariate analysis, age at
      surgery older than 60 years (P = .045), fine atrial fibrillation wave pattern (P
      = .033), and preoperative left atrial dimension greater than 60 mm (P = .019)
      were independent risk factors for atrial fibrillation recurrence, whereas type of
      mitral surgery was not (P = .573). Although transmitral A-wave prevalence did not
      differ significantly between groups beyond the early postoperative period, A-wave
      velocity was faster in the repair group through the entire postoperative period
      (P < .001). CONCLUSIONS: Maze outcomes were acceptable regardless of type of
      mitral surgery. Late atrial fibrillation recurrence was mainly affected by age,
      unfavorable electrocardiographic characteristics of atrial fibrillation, and
      larger preoperative left atrial size.

PMID- 19740490
TI  - Ascending aortic injury caused by a fractured sternal wire 28 years after
      surgical intervention of pectus excavatum.

PMID- 19740491
TI  - Composite chest wall reconstruction using titanium plates and mesh preserves
      chest wall function.

PMID- 19740492
TI  - Vagal denervation and reinnervation after ablation of ganglionated plexi.
AB  - OBJECTIVE: Surgical ablation of ganglionated plexi has been proposed to increase
      efficacy of surgery for atrial fibrillation. This experimental canine study
      examined electrophysiologic attenuation and recovery of atrial vagal effects
      after ganglionated plexi ablation alone or with standard surgical lesion sets for
      atrial fibrillation. METHODS: Dogs were divided into 3 groups: group 1 (n = 6)
      had focal ablation of the 4 major epicardial ganglionated plexi fat pads, group 2
      (n = 6) had pulmonary vein isolation with ablation, and group 3 (n = 6) had
      posterior left atrial isolation with ablation. All fat pads were ablated. Sinus
      and atrioventricular interval changes during bilateral vagosympathetic trunk
      stimulation were examined before and both immediately and 4 weeks after ablation.
      Vagally induced effective refractory period changes and mean QRST area changes
      (index of local innervation) were examined in 5 atrial regions. RESULTS: Sinus
      and atrioventricular interval changes and heart rate variability decreased
      immediately after ablation, but only sinus interval changes were restored
      significantly after 4 weeks in all groups. Ablation-modified vagal effects on
      effective refractory period or QRST area changed heterogeneously in groups 1 and
      2. In group 3, regional vagal effects were attenuated extensively postablation in
      both atria. Posterior left atrial isolation with ablation incrementally
      denervated the atria. In the long term, vagal stimulation increased QRST area
      changes relative to control values in all groups. Heart rate variability was also
      assessed. CONCLUSIONS: Ganglionated plexi ablation significantly reduced atrial
      vagal innervation. Restoration of vagal effects at 4 weeks suggests early atrial
      reinnervation.

PMID- 19740493
TI  - Is transapical aortic valve implantation really less invasive than minimally
      invasive aortic valve replacement?
AB  - BACKGROUND: Transcatheter valve implants currently draw their justification for
      use from reduction of perioperative risk. However, patient age and comorbidities
      are independent predictors of adverse outcome after aortic valve replacement,
      regardless of surgical approach. Therefore, it is unclear whether transapical
      aortic valve implantation really improves outcomes in high-risk patients.
      METHODS: We included a total of 51 high-risk patients with severe aortic valve
      stenosis. Patients were allocated to transapical aortic valve implantation (n =
      21) or minimally invasive aortic valve replacement via a partial upper sternotomy
      (n = 30), in a nonrandomized fashion. Patient age, preoperative comorbidities,
      and perioperative risk, expressed as logistic EuroSCORE (38% +/- 14% vs 35% +/-
      9%), were matched between the 2 groups. RESULTS: Early morbidity and mortality
      were comparable between groups, but transapical aortic valve implantation was
      associated with shorter operative time (P = .004), ventilation time (P < .001),
      intensive care unit stay (P < .001), and hospital stay (P < .001). Thirty-day
      mortality was 14% (n = 3) in the transcatheter group versus 10% (n = 3) in the
      surgical group. After a mean follow-up of 12 +/- 4 months (100% complete), there
      were a total of 5 (24%) deaths in the transapical group versus 5 (17%) deaths in
      the open surgery group. There was 1 intraoperative death in the transapical group
      versus none in the surgery group. In the transapical group, there were 2 re
      explorations for bleeding, 2 intraoperative conversions, 1 case of prosthesis
      migration, and 2 impairments of coronary arteries. The surgery group included 1
      re-exploration, 1 stroke, 1 pacemaker implantation for complete atrioventricular
      block, and 3 cases of atrial fibrillation. CONCLUSIONS: Current data suggest a
      faster postoperative recovery after transapical aortic valve implantation, with
      early and late morbidity and mortality comparable with those of minimally
      invasive aortic valve replacement via partial upper sternotomy.

PMID- 19740495
TI  - Bioremediation of petroleum hydrocarbons in anoxic marine sediments: consequences
      on the speciation of heavy metals.
AB  - We investigated the effects of biostimulation and bioagumentation strategies
      applied to harbor sediments displaying reducing conditions and high
      concentrations of petroleum hydrocarbons and heavy metals. We compared the
      microbial efficiency of hydrocarbon removal from sediments maintained for 60 days
      in anoxic conditions and inoculated with acetate, sulfate-reducing bacterial
      strains and acetate and sulfate-reducing bacteria. All treatments determined a
      significant increase in the microbial growth and significant decreases of
      hydrocarbon contents and of redox potential values. The addition of sulfate
      reducing bacterial strains to the sediment was the most efficient treatment for
      the hydrocarbon removal. In all experiments, significant changes of the heavy
      metals' phase repartition were observed. The results reported here suggest that
      the biodegradation of petroleum hydrocarbons in anoxic marine sediments may be
      enhanced by stimulating microbial anaerobic metabolism, but care should be
      applied to monitor the potential changes in the mobility and bioavailability of
      heavy metals induced by bio-treatments.

PMID- 19740496
TI  - The power of mutants for investigating jasmonate biosynthesis and signaling.
AB  - Mutant analysis includes approaches that range from traditional screening of
      mutant populations (forward genetics), to identifying mutations in known genes
      (reverse genetics), to examining the effects of site-specific mutations that
      encode modified proteins. All these methodologies have been applied to study
      jasmonate synthesis and signaling, and their use has led to important
      discoveries. The fad3 fad7 fad8 mutant of Arabidopsis, and other mutants
      defective in jasmonate synthesis, revealed the roles of jasmonate in flower
      development and plant defense against necrotrophic fungal pathogens. The coi1
      mutant identified the F-box protein that is now known to be the receptor for
      jasmonoyl-isoleucine, the active form of jasmonate hormone. Investigations of how
      JASMONATE-ZIM DOMAIN (JAZ) proteins bind to COI1 and facilitate jasmonate
      perception have relied on the jai3 mutant, on JAZDeltaJas constructs, and on site
      specific mutations in the Jas and ZIM domains of these proteins.

PMID- 19740497
TI  - Epidemiology of physical inactivity in Poland: prevalence and determinants in a
      former communist country in socioeconomic transition.
AB  - OBJECTIVES: The aim of this study was to identify physical activity patterns and
      determinants of physical inactivity in a representative sample of Polish adults.
      STUDY DESIGN: A cross-sectional analysis of 14 769 randomly selected individuals
      (52.7% women and 47.3% men) aged 20-74 years participating in the National Polish
      Health Survey, WOBASZ (2002-2005). METHODS: Sociodemographic and lifestyle
      details were collected. Assessment of physical activity was based on selected
      questions from the CINDI Health Monitor Questionnaire. RESULTS: Approximately 35%
      of Polish adults are not physically active in leisure time, whilst 39.5% declare
      sufficient level of leisure-time physical activity. Leisure-time inactivity is
      significantly less likely in persons aged <35 years, those with university
      education and those living in rural areas. Almost 48% of men and 28.4% of women
      employed full- or part-time report highly active work, whilst sedentary work is
      reported by 42.7% of women and 30.2% of men. Low occupational activity is more
      prevalent in young adults, persons with university education and those living in
      large urban areas. Nearly 67% of the entire working population report no active
      commuting. CONCLUSIONS: There is a need to promote various forms of physical
      activity, with special attention on active commuting and leisure-time activities
      across both genders and all age groups. Public health policies and programmes
      should focus on substantial differences between various sociodemographic groups.

PMID- 19740498
TI  - Let's talk about smear tests: social marketing for the National Cervical
      Screening Programme.
AB  - OBJECTIVES: The overall aim of the work was to increase participation by Maori
      and Pacific women in the National Cervical Screening Programme (NCSP) in New
      Zealand using a social marketing informed approach. Key objectives for this
      target group included: increasing awareness, understanding and discussion of
      cervical cancer and cervical screening; increasing telephone calls to the NCSP's
      0800 number; and increasing uptake of cervical screening. STUDY DESIGN: A social
      marketing intervention with mixed qualitative and quantitative evaluation.
      METHODS: Focus groups with priority women and key stakeholder interviews were
      used to identify a set of key messages from which television, radio and print
      media advertisements were developed. The advertising campaign was one element of
      a broader programme of activity, which involved changes to service delivery and
      improvement to access to services, particularly for the target groups. The
      campaign was evaluated in three ways: quantitative surveys conducted before,
      during and after the intervention; monitoring the number of calls to the NCSP's
      0800 number; and monitoring NCSP monthly coverage statistics. RESULTS: The social
      marketing intervention achieved measurable behavioural impacts with its primary
      target audiences, delivering significant increases in screening uptake by Maori
      (6.8%) and Pacific women (12.7%) after 12 months. In addition, there was a
      secondary positive impact on other women (not the immediate target audience)
      whose rate of update also increased (2.7%). Overall, the intervention helped to
      reduce inequalities and delivered substantial increases in awareness,
      understanding and discussion of cervical cancer and cervical screening amongst
      the target groups. CONCLUSIONS: The results demonstrate that social marketing can
      be effective in targeting marginalized or under-represented groups. The
      intervention has not only changed the way in which women in New Zealand talk
      about a previously 'taboo' subject, but it has also provided a platform for
      significant behaviour change which will help to reduce inequalities in the burden
      of cervical cancer.

PMID- 19740500
TI  - What has positron emission tomography told us about the epileptogenic zone?
AB  - There is no one ligand for visualising "the epileptogenic zone". Several PET
      ligands, however, can help by noninvasively or minimally invasively refining
      hypotheses regarding its location. Their relative merits depend not only on local
      availability and expertise, but also on epilepsy syndrome and overall diagnostic
      category. FDG, flumazenil (FMZ), alpha-methyl-tryptophan (AMT), the 5-HT1A
      ligands, and diprenorphine are discussed.

PMID- 19740501
TI  - Leishmania(Leishmania) chagasi in captive wild felids in Brazil.
AB  - This study used a PCR-RFLP test to determine the presence of Leishmania
      (Leishmania) chagasi in 16 captive wild felids [seven Puma concolor (Linnaeus,
      1771); five Panthera onca (Linnaeus, 1758) and four Leopardus pardalis (Linnaeus,
      1758)] at the zoological park of the Federal University of Mato Grosso, Brazil.
      Amplification of Leishmania spp. DNA was seen in samples from five pumas and one
      jaguar, and the species was characterized as L. chagasi using restriction
      enzymes. It is already known that domestic felids can act as a reservoir of L.
      chagasi in endemic areas, and further studies are necessary to investigate their
      participation in the epidemiological chain of leishmaniasis.

PMID- 19740502
TI  - A mixed malaria infection: is Plasmodium vivax good for you?
AB  - We describe a case of mixed malaria infection in a returning traveller. We
      suggest that our patient had a chronic infection with Plasmodium vivax, which
      reduced the severity of an acute infection with P. falciparum-an example of cross
      species immunity.

PMID- 19740504
TI  - Expedition medicine in the tropics: through heat and sleet.
AB  - Expeditionary travel-for the purposes of scientific discovery, personal
      challenge, or survival-represents an essential human instinct. Risks come with
      the territory although not all the risks can be anticipated. This is part of the
      appeal of exploration. Risks can be minimised through proper planning and
      preparation. High risk appetite does not necessarily mean recklessness. For the
      expedition medic, behavioural modification and communication skills are every bit
      as important as clinical acumen. Extreme endurance events and unfamiliar
      surroundings provide both physical and mental challenges. These challenges are
      not uncommonly exploited by consumer reality television shows when novices are
      placed in such situations. Studies of human adaptation to extreme environments,
      such as at or near the summit of Everest, may provide new insights into human
      physiology that could translate into important medical interventions. Working in
      extreme environments-such as in tropical jungle heat or within Everest's 'death
      zone'-presents unique challenges but it also brings unique rewards and discovery.
      As long as humans have the urge to explore, whatever perils lie ahead boredom
      will not be one of them.

PMID- 19740503
TI  - Mode of action and choice of antimalarial drugs for intermittent preventive
      treatment in infants.
AB  - Intermittent preventive treatment in infants (IPTi) is an effective and safe
      malaria control strategy. However, it remains unclear what antimalarials should
      be used to replace sulfadoxine-pyrimethamine (SP) when and where SP is no longer
      an effective drug for IPTi. Work recently conducted in Tanzania, combined with
      the findings of previous studies, indicates that IPTi is essentially intermittent
      chemoprophylaxis; consequently, long-acting antimalarials that provide a long
      period of post-treatment prophylaxis will be the most effective alternative to
      SP. However, because of concerns about development of drug resistance, new
      combinations of long-acting drugs are urgently needed.

PMID- 19740505
TI  - Biological effects of combined ultrasound and cisplatin treatment on ovarian
      carcinoma cells.
AB  - The effects of low-power ultrasound, the anti-cancer drug cisplatin, and their
      combined application were studied in two lines of human ovarian carcinoma cells,
      A2780 and A2780cis. Four modes of treatment were used: exposure to ultrasonic
      field, application of cisplatin, exposure to ultrasound followed by cisplatin,
      and presence of cisplatin followed by exposure to application ultrasound.
      Ultrasound was used at intensities of 0.5 W/cm(2) and 1.0 W/cm(2) for 10 min,
      cisplatin was applied at concentrations of 1 microM and 6 microM per cell
      suspension treated in A2780 and cisplatin-resistant A2780cis cells, respectively.
      The results of each experimental treatment were assessed by the resultant cell
      viability related to the viability of control cells, using a standard MTT test.
      It was shown that a combined effect of ultrasound and cisplatin was more
      effective than that of ultrasound or cisplatin alone. It also appeared that the
      order of application played a role, with the cisplatin-ultrasound treatment
      lowering cell viability more than the ultrasound-cisplatin treatment. It can be
      assumed that the exposure of cells to a low-power ultrasonic field has an
      immediate effect on the structure of cell surfaces and, consequently, on entry of
      cisplatin into the cell. The study also included observations on changes in the
      cell cycle associated with the treatments used in both cell lines and their
      evaluation by flow cytometry.

PMID- 19740506
TI  - High frequency shear ultrasonic properties of water/sorbitol solutions.
AB  - Dynamic viscoelastic properties (G' and G''), ultrasonic shear velocity and
      attenuation were measured for aqueous solutions of sorbitol at 5 MHz. For pure
      sorbitol, the shear ultrasonic velocity reached 1470 ms(-1) with a density of
      1500 kgm(-3), consequently leading to a high acoustical impedance compared with
      "classical" polymers (polystyrene, nylon, polyethylene, Teflon, etc.). We
      demonstrate that this surprisingly high shear ultrasonic velocity for a
      viscoelastic material was due to the fact that the glass transition begins at a
      concentration above 85% of sorbitol in water. Hence, pure sorbitol is an ideal
      coupling material for high frequency shear experiments.

PMID- 19740507
TI  - Recombination, selection and clock-like evolution of Rice yellow mottle virus.
AB  - The clock-like diversification of Rice yellow mottle virus (RYMV), a widespread
      RNA plant virus that infects rice in Africa, was tested following a three-step
      approach with (i) an exhaustive search of recombinants, (ii) a comprehensive
      assessment of the selective constraints over lineages, and (iii) a stepwise
      series of tests of the molecular clock hypothesis. The first evidence of
      recombination in RYMV was found in East Africa, in the region most favorable to
      co-infection. RYMV evolved under a pronounced purifying selection, but the
      selection pressure did vary among lineages. There was no phylogenetic evidence of
      transient deleterious mutations. ORF2b, which codes for the polymerase and is the
      most constrained ORF, tends to diversify clock-like. With the other ORFs and the
      full genome, the departure from the strict clock model was limited. This likely
      reflects the dominant conservative selection pressure and the clock-like fixation
      of synonymous mutations.

PMID- 19740508
TI  - A cell-permeable peptide inhibits hepatitis C virus replication by sequestering
      IRES transacting factors.
AB  - Hepatitis C virus (HCV) infection frequently leads to chronic hepatitis, liver
      cirrhosis, and hepatocellular carcinoma. There is no effective therapy or vaccine
      available to HCV-infected patients other than interferon-ribavarin combination,
      which is effective in a relatively small percentage of infected patients. Our
      previous results have shown that a synthetic peptide (LAP) corresponding to the N
      terminal 18 amino acids of the Lupus autoantigen (La) was a potent inhibitor of
      HCV IRES-mediated translation. We demonstrate here that LAP efficiently blocks
      HCV replication of infectious JFH1 virus in cell culture. Our data suggest that
      LAP forms complexes with IRES-transacting factors (ITAFs) PTB and PCBP2. LAP
      mediated inhibition of HCV IRES-mediated translation in vitro could be fully
      rescued by recombinant PCB and PCBP2. Also transient expression of PTB / PCBP2
      combination significantly restores HCV replication in LAP-inhibited cultures.
      These results suggest that ITAFs could be potential targets to block HCV
      replication.

PMID- 19740509
TI  - Assessing TNT and DNT groundwater contamination by compound-specific isotope
      analysis and 3H-3He groundwater dating: a case study in Portugal.
AB  - Trinitrotoluene (TNT) and dinitrotoluene (DNT) originating from 50 years of
      explosives production have heavily contaminated two stacked aquifers in the
      vicinity of Lisboa, Portugal. To assess if these poly-nitroaromatic compounds (P
      NACs) are being degraded in the subsurface, tracer-based groundwater dating
      techniques combined with compound-specific isotope analyses (CSIA) were applied.
      The groundwater residence times were distinctly different in the two aerobic
      aquifers, as determined by the tritium ((3)H)-(3)He method. In the contaminated
      zones, the upper aquifer exhibited groundwater ages of 25 years, whereas the
      lower (presumably confined) aquifer contained hardly any tritium which indicates
      water ages >55 years. P-NACs-containing waste waters are known to have leaked
      into the upper, unconfined aquifer. However, P-NACs were present in both aquifers
      in high concentrations (up to 33000 microg L(-1) TNT), which implies a hydraulic
      connection, although tritium concentrations and chemical data suggest two
      separated aquifers. Based on the (3)H-(3)He groundwater dating and the presence
      of very high P-NAC concentrations, the contamination of the lower aquifer must
      have happened during the early stage of the explosive production, i.e. >50 years
      ago. Despite this 'old' contamination, TNT and DNT have not been transformed
      until to date as is demonstrated by the negligible changes in their carbon
      isotopic signatures (delta(13)C). Thus, P-NACs are very recalcitrant to
      degradation at the investigated site. If the aquifers remain aerobic, TNT and DNT
      are expected to persist in the subsurface for many decades to centuries. The
      presented approach of assessing time scales of natural attenuation at the field
      scale by the combination of CSIA and (3)H-(3)He water dating has the potential to
      be applied to any other groundwater contaminants, such as chlorinated
      hydrocarbons, gasoline components, heterocyclic carbenes, or polyaromatic
      hydrocarbons.

PMID- 19740510
TI  - Degradation of sulfide linkages between isoprenes by lipid peroxidation catalyzed
      by manganese peroxidase.
AB  - Scission of sulfide linkages in vulcanized rubber has been a major concern since
      the early 20th century, because devulcanization is a key process for recycling
      waste rubber products as polymer materials that pose low environmental risks. We
      herein demonstrate that lipid peroxidation (LPO) of linoleic acid by manganese
      peroxidase (MnP), a proposed lignin-degradation system in the early stage of
      selective white rot fungi, cleaves sulfide bond in a model rubber compound, di(2
      methylpent-2-enyl) sulfide, to 2,4-dimethylthiophene and 2-methyl-2-pentenal. The
      major intermediate of the LPO process, 2,4-decadienal was directly oxidized by
      MnP to cleave the sulfur-carbon bond. We propose that electrophilic radicals from
      2,4-decadienal abstract one electron from a sulfur atom of the model compound to
      produce the sulfur radical cation intermediate, which in turn reacts with
      molecular oxygen to cleave the sulfur-carbon bond. The discovery of free radical
      mediated scission of sulfide bond coupled with Mn oxidation provides a novel
      strategy for recycling vulcanized rubber wastes.

PMID- 19740511
TI  - Steelmaking slag as aggregate for mortars: effects of particle dimension on
      compression strength.
AB  - The present paper reports on the results of some experiments obtained from the
      production, hydration and subsequent measurement of the mechanical properties of
      several mortars prepared using a commercial CII/B-LL Portland cement, steelmaking
      slag, superplasticizer and water. Relevant parameters for the mortar preparation
      are the weight ratios of cement/water, the weight ratio superplasticizer/cement
      and between fine and granulated coarse particles. It has been demonstrated that
      optimisation of such parameters leads to the production of materials with
      mechanical properties suitable for civil engineering applications. Moreover,
      materials with improved compressive strength can be prepared by the use of slag
      containing extensive amounts of large particles.

PMID- 19740512
TI  - Stack gas emissions of PCDD/Fs from hospital waste incinerators in China.
AB  - Stack gas samples from 14 domestic-made hospital waste incinerators (HWIs) in
      China were collected and analyzed for polychlorinated dibenzo-p-dioxins and
      dibenzofurans (PCDD/Fs). The waste burning capacities of the investigated HWIs
      ranged from 5 to 25 ton d(-1). The stack gas emissions of PCDD/Fs from HWIs
      exhibited a large variation (0.08-31.60 ng I-TEQNm(-3)). Nine incinerators had
      the emission levels below the current emission standard in China (0.5 ng I-TEQN
      m(-3)), while only two facilities exhibited emission levels below the European
      Union directive emission limit (0.1 ng I-TEQN m(-3)). For two plants,
      concentrations of PCDD/Fs in stack gas were above 10.0 ng I-TEQN m(-3). The
      emission factors of PCDD/Fs from the investigated HWIs were in the range of 0.78
      473.97 microg I-TEQ ton(-1) medical wastes. It was estimated that 4.87 g I-TEQ of
      PCDD/Fs was annually released from HWIs to the atmosphere in China in 2006.
      Principal component analysis and hierarchical cluster analysis were applied to
      analyze the congener profiles of PCDD/Fs from HWIs in China.

PMID- 19740513
TI  - A comparison of EGFR and KRAS status in primary lung carcinoma and matched
      metastases.
AB  - Epidermal growth factor receptor (EGFR) and v-Ki-ras 2 (KRAS; viral Kirsten rat
      sacoma 2 oncogene homolog) oncogenes are predictors of response to EGFR-targeted
      therapy in lung carcinomas. Morphologic heterogeneity of lung carcinomas is
      reflected at the molecular level and may confound interpretation of
      immunohistochemistry, fluorescence in situ hybridization, and mutational assays,
      which are all used for analysis of KRAS and EGFR genes. Furthermore, molecular
      characteristics may differ between the primary tumor and corresponding
      metastases. The aim of this study was to determine if the KRAS and/or EGFR status
      of primary and metastatic lung carcinoma differs. Three hundred thirty-six cases
      of primary lung carcinomas were tested for EGFR and KRAS, and 85 cases had a
      metastasis (25%). Of the 40 cases (47%) with sufficient material for EGFR and
      KRAS mutational analysis, there were 11 (27.5%) primary tumors and 4 (10%)
      metastases identified with a KRAS mutation. Of the cases with EGFR fluorescence
      in situ hybridization results, there were 3 (8%) primary tumors and 8 (24%)
      metastases that were fluorescence in situ hybridization positive. Overall, there
      were 9 cases (22.5%) with discordant KRAS status and 11 cases (32.5%) with
      discordant EGFR fluorescence in situ hybridization status. Our results suggest
      that the EGFR and KRAS status of primary lung carcinomas may not predict the
      status in the corresponding metastases. This observation may have important
      implications for molecular testing for targeted therapies.

PMID- 19740514
TI  - The role of Reg IV gene and its encoding product in gastric carcinogenesis.
AB  - Although the biologic function of Reg IV is poorly understood, it has been
      reported that Reg IV is a potent activator of the epidermal growth factor
      receptor/Akt/AP-1 signaling pathway in colon cancer cells and closely linked with
      the inhibition of apoptosis. To clarify the role of Reg IV in gastric
      carcinogenesis and subsequent progression, we examined its expression by
      immunohistochemistry and in situ hybridization on tissue microarray containing
      gastric carcinoma, adjacent nonneoplastic mucosa, adenoma, intestinal metaplasia,
      or gastritis. Gastric carcinoma cell lines (MKN28, AGS, MKN45, KATO-III, and HGC
      27) were studied for Reg IV expression by Western blot and reverse transcriptase
      polymerase chain reaction followed by sequencing. Frozen samples of gastric
      carcinoma and adjacent nonneoplastic mucosa were subjected to Western blot, and
      patient serum, to enzyme-linked immunosorbent assay for Reg IV. Gastric carcinoma
      cell lines showed different levels of Reg IV mRNA and its encoding protein. The
      Reg IV protein expression was gradually decreased from intestinal metaplasia,
      adenoma, and carcinoma to gastritis (P < .05). The positive rate of its mRNA was
      higher in intestinal metaplasia than carcinoma or nonneoplastic mucosa (P < .05).
      Elevated serum Reg IV level in gastric carcinoma patients was detected in
      comparison with that in health individuals (P < .05). Reg IV expression was
      significantly correlated with the MUC-2 and MUC-5AC expression (P < .05). Among
      histologic subtypes of the World Health Organization, signet ring cell carcinoma
      more frequently expressed Reg IV than the others (P < .05), whereas it is the
      converse for the poorly differentiated group (P < .05). Our study indicated that
      Reg IV expression experienced up-regulation in gastric intestinal metaplasia and
      adenoma and then down-regulation with malignant transformation of gastric
      epithelial cells. It was suggested that Reg IV expression should be considered as
      a good biomarker for gastric precancerous lesions and was especially related to
      the histogenic pathway of signet ring cell carcinoma.

PMID- 19740515
TI  - Small blue cells mimicking small cell carcinoma in spermatocele and hydrocele
      specimens: a report of 5 cases.
AB  - We identified 5 cases of hydrocele and spermatocele resections containing
      detached small cellular "blue" clusters, raising questions of small cell
      carcinoma by contributors to our consult service. Patients were 37, 39, 52, 67,
      and 70 years old. None of the 4 patients with follow-up developed small cell
      carcinoma. On routine stained sections, there were multiple clusters of detached
      hypercellular cells with focal streaming, high nuclear-to-cytoplasmic ratios, and
      hyperchromatic nuclei without prominent nuclei. There were no mitotic figures,
      apoptotic bodies, or necrosis. In 4 of 5 cases, there was sufficient tissue to
      perform immunohistochemistry along with 10 cases each of normal rete testis and
      epididymis. CD56 was positive in 4 of 4 cases of the "blue cells" and in 9 of 10
      of normal rete testis; yet, it was positive in only 2 of 10 normal epididymis.
      Synaptophysin and chromogranin were negative in all cases of "blue cells." PAX2
      was negative in all cases of "blue cells" similar to the 1 of 9 positive staining
      in rete testis and in contrast to the positivity seen in 9 of 9 cases of normal
      epididymis. Ki-67 was negative or showed only rare positive cells in all of the
      cases of the "blue cells." Clusters of blue cells suggestive of sloughed rete
      testis cells can mimic small cell carcinoma in hydrocele and spermatocele
      specimens based on their low power appearance and positive CD56 staining. Closer
      examination of the cells' bland morphology, low expression of Ki-67, and lack of
      chromogranin and synaptophysin, along with recognition of this entity, can
      prevent a misdiagnosis of malignancy.

PMID- 19740516
TI  - Napsin A and thyroid transcription factor-1 expression in carcinomas of the lung,
      breast, pancreas, colon, kidney, thyroid, and malignant mesothelioma.
AB  - Recent advances in the treatment of pulmonary adenocarcinoma have increased the
      need for accurate typing of non-small cell carcinomas. Immunohistochemistry for
      thyroid transcription factor-1 is widely used in the diagnosis of pulmonary
      adenocarcinomas because it marks approximately 75% of lung adenocarcinomas and is
      negative in most squamous cell carcinomas and adenocarcinomas of other organs.
      Napsin A is an aspartic proteinase involved in the maturation of surfactant
      protein B. It is detected in the cytoplasm of type 2 pneumocytes and alveolar
      macrophages and is a putative marker for pulmonary adenocarcinomas. We performed
      immunohistochemistry for napsin A and thyroid transcription factor-1 using tissue
      microarrays of 95 adenocarcinomas, 48 squamous cell carcinomas, 6 neuroendocrine
      tumors of the lung, as well as 5 colonic, 31 pancreatic, and 17 breast
      adenocarcinomas, 38 malignant mesotheliomas, 118 renal cell carcinomas, and 81
      thyroid tumors. The tissue microarrays also included 15 different benign tissues.
      Pulmonary adenocarcinomas were napsin A positive in 79 (83%) of 95 cases compared
      with 69 (73%) of 95 cases that were thyroid transcription factor-1 positive.
      There were 13 napsin A-positive/thyroid transcription factor-1-negative and 2
      thyroid transcription factor-1-positive/napsin A-negative tumors, increasing the
      number of cases that were positive with at least one of the markers to 81 (85%)
      of 95. The limited number of neuroendocrine tumors tested was napsin A negative.
      All squamous cell carcinomas, adenocarcinomas of the colon, pancreas and breast,
      and mesotheliomas were negative for both markers. Of the renal tumors, napsin A
      was positive in most of papillary renal cell carcinomas (79%), about one third
      (34%) of clear cell renal cell carcinomas, and in a single case of chromophobe
      renal cell carcinoma (3%). In the thyroid, only 2 cases of papillary thyroid
      carcinoma (5%), both with tall cell morphology, were positive for napsin A,
      whereas all other papillary and follicular carcinomas were negative. As expected,
      all renal tumors were thyroid transcription factor-1 negative, and all thyroid
      tumors, except for one papillary carcinoma, were thyroid transcription factor-1
      positive. Napsin A is a sensitive marker for pulmonary adenocarcinoma and is also
      expressed in a subset of renal cell carcinomas, particularly of the papillary
      type, as well as in rare cases of papillary thyroid carcinomas. The combined use
      of napsin A and thyroid transcription factor-1 results in improved sensitivity
      and specificity for identifying pulmonary adenocarcinoma in primary lung tumors
      and in a metastatic setting.

PMID- 19740517
TI  - Follicular dendritic cell sarcoma with immature T-cell proliferation.
AB  - Follicular dendritic cell sarcoma is characterized by proliferation of spindled
      to ovoid cells reminiscent of follicular dendritic cells. However, the
      association of follicular dendritic cell sarcoma with a dense infiltration of
      immature T cells has not hitherto been reported. We report an unusual case of
      follicular dendritic cell sarcoma of the mesentery with immature T-cell
      proliferation in a 68-year-old man. The infiltrating immature T cells
      demonstrated expression of CD3, CD1a, TdT, and coexpression of CD4 and CD8 by
      immunohistochemistry. In addition, the patient was subsequently diagnosed with
      myasthenia gravis and paraneoplastic pemphigus and died of distant metastasis
      within 2 years after initial diagnosis of follicular dendritic cell sarcoma. The
      aggressive clinical course of this case contrasts with the indolent course of
      follicular dendritic cell sarcomas, and thus, the prognostic implications of
      follicular dendritic cell sarcoma with immature T-cell proliferation require
      clarification. The complication of myasthenia gravis and paraneoplastic pemphigus
      may suggest that immature T-cell proliferation has an autoimmunity-related
      systemic influence.

PMID- 19740518
TI  - Urokinase-type plasminogen activator is a marker of aggressive phenotype and an
      independent prognostic factor in mismatch repair-proficient colorectal cancer.
AB  - The aim of this study was to determine the prognostic significance of urokinase
      type plasminogen activator (uPA) and its receptor (uPAR) in colorectal cancer
      stratified by mismatch repair status and to determine their contribution to the
      aggressive phenotype predicted by loss of E-cadherin and apoptosis protease
      activating factor-1 (APAF-1). Immunohistochemistry for uPA and uPAR was performed
      on a tissue microarray comprising 811 mismatch repair-proficient and 164 mismatch
      repair-deficient colorectal cancers. Immunoreactivity was scored
      semiquantitatively and the interobserver agreement between multiple pathologists
      was determined. Optimal cutoff scores for uPA and uPAR positivity were obtained
      by receiver operating characteristic curve analysis. Agreement between
      pathologists was excellent for uPA and uPAR. Cutoff scores of 60% for uPA and 75%
      for uPAR were validated by resampling of the data. In mismatch repair-proficient
      colorectal cancer, overexpression of uPA and uPAR was associated with advanced pT
      stage (P = .009, both), an infiltrating margin (P = .009 and P = .033,
      respectively), and poor prognosis (P = .002 and P < .001, respectively). uPA, but
      not uPAR, maintained its significant prognostic effect in multivariable analysis
      (P = .037). In addition to loss of APAF-1 (P = .002) and E-cadherin (P < .001),
      uPA independently predicted an infiltrating margin (P = .016). Our findings
      suggest that uPA, but not uPAR, is an independent prognostic factor and that this
      negative effect on survival is relevant specifically for mismatch repair
      proficient colorectal cancers. Moreover, the combination of uPA with E-cadherin
      and APAF-1 is linked to an aggressive tumor phenotype and highly predictive of an
      infiltrating growth pattern.

PMID- 19740519
TI  - Angioimmunoblastic T-cell lymphoma in bone marrow: a morphologic and
      immunophenotypic study.
AB  - Angioimmunoblastic T-cell lymphoma is known to frequently involve bone marrow.
      However, the histologic and immunophenotypic features of angioimmunoblastic T
      cell lymphoma at this site are poorly defined. We assessed 27 bone marrow
      specimens involved by angioimmunoblastic T-cell lymphoma from 20 patients.
      Histologically, bone marrow involvement was predominantly multifocal (74%) and
      exhibited a nodular pattern (78%), often associated with other patterns. Using
      immunohistochemistry, programed death-1 and CD10 were expressed by atypical
      lymphocytes in 17 (85%) of 20 and 5 (18.5%) of 27 specimens, respectively. CXCL13
      was not expressed by atypical lymphocytes in all cases but did stain stromal
      cells consistent with follicular dendritic cells in 1 case. BCL-6 as a single
      antibody was difficult to interpret because many normal bone marrow cells are
      dimly positive, but BCL-6/CD3 dual staining highlighted BCL-6+ T-cells in all
      cases assessed. Antibodies specific for CD21 and CD35 did not highlight
      follicular dendritic cells in any biopsy specimens. Flow cytometry
      immunophenotyping revealed a CD3+CD10+ T-cell population in 2 (25%) of 8 cases
      assessed. We conclude that the recognition and classification of
      angioimmunoblastic T-cell lymphoma in bone marrow are made difficult by the
      uncommon expression of CD10 (25%), rarity of follicular dendritic cells, and lack
      of CXCL13 expression at this site. This is most likely attributable to the very
      different microenvironment of the bone marrow relative to lymph nodes and, in
      particular, the absence of follicles in bone marrow. By contrast, programed death
      1 immunohistochemical staining and double labeling using antibodies specific for
      BCL-6 and CD3 were helpful in appreciating the follicular T-helper cell
      immunophenotype of angioimmunoblastic T-cell lymphoma.

PMID- 19740520
TI  - Contributions of pediatrics and pediatric pathology to the body of knowledge
      regarding human disease.
AB  - A century or so ago, pediatrics and pediatric pathology did not exist. Then, many
      fetuses/newborns died in utero or shortly after birth. With time, the issue of
      sepsis was addressed, and a greater number of newborns survived. Gradually, in
      this soil, the disciplines of pediatrics and pediatric nursing arose, as some
      recognized that infants were not merely small adults but were, in fact, quite
      different. Years later, pediatric pathology developed as a field of exploration.
      Today, pediatric pathology is a specialty, as witnessed by training programs,
      societies devoted to research and education, an expanding number of textbooks and
      innovative research. Pediatric pathology is distinct from adult pathology, as
      seen by the diversity of malformations and metabolic diseases stemming from
      mutations, the immaturity of the newborn's immune system, and the types of
      neoplasms germane to infants and children. Much of the progress in these areas
      was facilitated by the simultaneous emergence of cytogenetics and molecular
      biology and their powerful tools of investigation. The latter were applied in a
      synergistic fashion to a major extent in maternity clinics and children's
      hospitals by, among others, molecular biologists, clinical geneticists,
      cytogeneticists, pediatricians, and pediatric pathologists. This article
      describes a select but small number of the many contributions of pediatrics and
      pediatric pathology to the current body of medical knowledge.

PMID- 19740521
TI  - The evolution and cultural transmission of percussive technology: integrating
      evidence from palaeoanthropology and primatology.
AB  - We bring together the quite different kinds of evidence available from
      palaeoanthropology and primatology to better understand the origins of Plio
      Pleistocene percussive technology. Accumulated palaeoanthropological discoveries
      now document the Oldowan Complex as the dominant stone tool making culture
      between 2.6-1.4 Ma, the earlier part of this contemporaneous with pre-Homo
      hominins. The principal types of artefacts and other remains from 20 Early Stone
      Age (Oldowan and earliest Acheulean) localities in Africa and elsewhere are
      reviewed and described. To better understand the ancestral behavioural
      foundations of this early lithic culture, we examine a range of recent findings
      from primatology. In particular, we attempt to identify key shared
      characteristics of Homo and Pan that support inferences about the preparedness of
      our common ancestor for the innovation of stone tool culture. Findings of
      particular relevance include: (i) the discovery of an expanding repertoire of
      percussive and other tool use based on directed use of force among wild
      chimpanzees, implicating capacities that include significant innovatory potential
      and appreciation of relevant causal factors; (ii) evidence of material cultural
      diversity among wild chimpanzees, indicating a readiness to acquire and transmit
      tool use innovations; and (iii) experimental studies of social learning in
      chimpanzees and bonobos that now encompass the acquisition of nut cracking
      through observation of skilled use of hammers and anvils by conspecifics, the
      diffusion within and between groups of alternative styles of tool use, and the
      adoption of free-hand stone-to-stone percussion to create useful flakes for
      cutting to gain access to food resources. We use the distributions of the
      inferred cultural traits in the wild to assess how diffusion relates to
      geographic distances, and find that shared traits drop by 50% from the
      approximately eight characteristic of close neighbours over a distance of
      approximately 700 km. This pattern is used to explore the implications of
      analogous processes operating in relation to Early Stone Age sites.

PMID- 19740522
TI  - Artefacts of apes, humans, and others: towards comparative assessment and
      analysis.
AB  - This paper explores issues of technology and artefacts in a comparative cross
      species frame, using archaeological examples and modern data sets to illustrate
      points about process and content. It develops the argument that regardless of
      species, artefacts have a special significance as external projections of the
      mind, often necessitating cognitive judgements on the basis of several variables
      and subject to influences by cultural tradition, functional needs, and raw
      materials. In humans, apes, and other tool using animals, behaviour overlaps in
      some respects and is vastly different in others. Overlapping aspects are worth
      seeking out and exploiting, as they provide opportunities to investigate factors
      influencing variation and to gain insights into cognition. Recent primatological
      research establishes much more foundation for continuity, but many of the details
      of artefacts and their variation remain to be explored. This paper presents case
      studies of variability and standardisation that suggest the limits on variation
      are as tight in some chimpanzee produced artefacts as in many produced by humans,
      and functional constraints appear to operate more strongly on some parts of
      artefacts than others. Thus, degree of standardisation cannot be used as a simple
      index to 'refinement,' but the widespread overlap in standardisation between
      human and nonhuman artefacts greatly expands the scope for study.

PMID- 19740523
TI  - Estimation of personal NO2 exposure in a cohort of pregnant women.
AB  - There is a growing concern about the possible adverse effects of exposure to air
      pollution on health during pregnancy. Therefore, a priority of the INMA
      (environment and childhood) study was to estimate personal exposure to traffic
      related air pollution. In the cohort from Valencia (n=855), ambient levels of
      NO(2) were measured at 93 sampling sites spread over the study area during four
      different sampling periods of 7 days each. Multiple regression models were used
      to map ambient NO(2) over the area. Geographical data and predictions from
      kriging obtained by the "let one out" procedure were used as predictors.
      Individual exposure was assigned as 1) the estimated ambient NO(2) level at the
      home address and 2) the average of estimated ambient NO(2) levels at home and
      work addresses, weighted by the time spent in each environment. Estimations were
      temporally customized using the NO(2) levels registered daily by the regional Air
      Pollution Monitoring Network. The entire pregnancy and each trimester were taken
      as exposure windows. The model for the mean levels of NO(2) during the sampling
      periods explained 81% of the variation in NO(2) levels. Relative percent
      differences between the two models of personal exposure assignment were less than
      9% for more than 90% of the participants; however the rest of them showed marked
      differences. Personal exposure estimates were slightly higher in the second
      model. In both cases, exposure during the whole pregnancy was strongly correlated
      with exposure in the second trimester. Considering periods shorter than the
      entire pregnancy will provide us the opportunity to identify specific windows of
      susceptibility.

PMID- 19740524
TI  - Bioaccessibility of mercury from traditional northern country foods measured
      using an in vitro gastrointestinal model is independent of mercury concentration.
AB  - Human health risk assessment of dietary mercury (Hg) exposure in Canada assumes
      that all Hg from fish consumption is in the form of methylmercury (MeHg), the
      more bioavailable and hazardous form of Hg. In contrast, the risk assessment of
      dietary Hg to Inuit in northern Canada assumes that no more than two-thirds of
      dietary Hg is MeHg since mammal organs consumed by Inuit contain substantial
      concentrations of inorganic Hg. In vitro gastrointestinal models (e.g., the
      Simulator of the Human Intestinal Microbial Ecosystem) are often used for the
      evaluation of soil contaminant bioaccessibility, i.e., the fraction solubilized
      into gastrointestinal fluids, for use in site-specific human health risk
      assessment. In this research, we digested northern country foods using the SHIME
      for the measurement of Hg bioaccessibility, a novel approach for the assessment
      of dietary Hg bioavailability. We demonstrated that small intestinal Hg
      bioaccessibility from 16 fish, wild game, and marine mammal samples consumed by
      Inuit in northern Canada ranged between 1 and 93% and was independent of food HgT
      (MeHg+Hg(II)) concentration. Additionally, we demonstrated that gastrointestinal
      microbes may affect Hg bioaccessibility of the 16 country foods, either
      increasing or decreasing bioaccessibility depending upon the type of food. These
      results indicate that gastrointestinal absorption of Hg is not likely limited by
      the concentration of Hg in the food, which is in agreement with in vivo Hg
      bioavailability studies. Furthermore, these in vitro results support the
      hypothesis that the gastrointestinal absorption of Hg from Inuit country foods is
      dependent upon food type.

PMID- 19740525
TI  - Univariate statistical analysis of environmental (compositional) data: problems
      and possibilities.
AB  - For almost 30 years it has been known that compositional (closed) data have
      special geometrical properties. In environmental sciences, where the
      concentration of chemical elements in different sample materials is investigated,
      almost all datasets are compositional. In general, compositional data are parts
      of a whole which only give relative information. Data that sum up to a constant,
      e.g. 100 wt.%, 1,000,000 mg/kg are the best known example. It is widely neglected
      that the "closure" characteristic remains even if only one of all possible
      elements is measured, it is an inherent property of compositional data. No
      variable is free to vary independent of all the others. Existing transformations
      to "open" closed data are seldom applied. They are more complicated than a log
      transformation and the relationship to the original data unit is lost. Results
      obtained when using classical statistical techniques for data analysis appeared
      reasonable and the possible consequences of working with closed data were rarely
      questioned. Here the simple univariate case of data analysis is investigated. It
      can be demonstrated that data closure must be overcome prior to calculating even
      simple statistical measures like mean or standard deviation or plotting graphs of
      the data distribution, e.g. a histogram. Some measures like the standard
      deviation (or the variance) make no statistical sense with closed data and all
      statistical tests building on the standard deviation (or variance) will thus
      provide erroneous results if used with the original data.

PMID- 19740526
TI  - A family having type 2B von Willebrand disease with an R1306W mutation: Severe
      thrombocytopenia leads to the normalization of high molecular weight multimers.
AB  - In type 2B von Willebrand disease (2B VWD), abnormal von Willebrand factor (VWF)
      spontaneously binds to platelets. This leads to the clearance of the high
      molecular weight multimers (HMWM) of VWF and results in thrombocytopenia. Herein
      we report a family of 2B VWD with an R1306W mutation which caused
      thrombocytopenia with giant platelets. The most important finding in this study
      is dynamic changes in VWF values in association with platelet counts. When the
      proband (2 years of age) had severe thrombocytopenia, his HMWM were normal,
      however, hematological examination showed a low level of VWF and a lack of HMWM
      after platelet count recovered. His affected sister also exhibited similar
      phenomenona. These results suggest that the severe thrombocytopenia leads to
      decreased clearance of VWF HMWM and restoration of VWF HMWM in plasma. We must
      consider 2B VWD in the case of recurrent thrombocytopenia following infection or
      other stress condition.

PMID- 19740527
TI  - Topical lidocaine and the effect on enoxaparin absorption in children: a pilot
      study.
AB  - Enoxaparin, a low molecular weight heparin (LMWH), is frequently used for the
      prevention and treatment of thromboembolic complications in infants and children
      (Sutor et al., 2004 [1]). Injection pain and the fear and anxiety associated with
      needle phobia in the pediatric population are well documented. Best practice
      pediatric pain management standards of care recommend mitigating the child's pain
      experience whenever possible. The use of topical anesthetics such as liposomal
      lidocaine 4% results in a rapid onset of anesthesia, minimal blanching, without
      vasoconstriction (Koh et al., 2004 [2]) or risk of methemoglobinemia. Topical
      lidocaine has been used to reduce the injection pain of enoxaparin, but there is
      no data available examining whether it will interfere with the absorption of
      LMWH. OBJECTIVE: To determine if the topical lidocaine, Maxilene, interferes with
      enoxaparin absorption as measured by peak anti-Xa levels. METHODS: Infants and
      children clinically prescribed enoxaparin were eligible for this study. Children
      in group 1 were pre-treated with Maxilene prior to enoxaparin injection on day 1
      with no Maxilene pre-treatment on day 2. For group 2, the order was reversed.
      Peak anti-Xa levels were measured following each enoxaparin dose and were
      compared between the groups. RESULTS: 26 children of ages 14d-16 y (median 6.7
      months) were enrolled. Anti-Xa levels following topical lidocaine administration
      were 0.070 U/mL (95%CI 0.025; 0.114) lower than without prior topical lidocaine
      administration. Anti-Xa levels on the second day were on average 0.013 U/mL
      (95%CI -0.066; 0.040) higher compared to day one regardless of the order of
      topical lidocaine administration. There were no reported incidences of local
      reactions such as redness, hives or blanching. CONCLUSIONS: Topical lidocaine
      (Maxilene) administration before enoxaparin injection results in a small,
      clinically non-significant, reduction in anti-Xa levels.

PMID- 19740528
TI  - Assessment of the risk of bleeding in patients undergoing surgery or invasive
      procedures: Guidelines of the Italian Society for Haemostasis and Thrombosis
      (SISET).
AB  - SYNOPSIS OF RECOMMENDATIONS: The Italian Society for Thrombosis and Haemostasis
      (SISET: Societa Italiana per lo Studio dell' Emostasi e della Trombosi) promoted
      the development of a series of guidelines which would adopt evidence-based
      medicine methodology on clinically relevant problems in the field of haemostasis
      and thrombosis. The objective of the present guidelines is to provide
      recommendations for the pre-operative and pre-procedural assessment of the
      bleeding risk with the aim of reducing the incidence of preventable bleeding
      complications and limiting laboratory tests to the those necessary. The
      predictive value of haemostatic tests for bleeding complications after surgery or
      invasive procedures has been evaluated in prospective or retrospective cohort
      studies only. All retrieved studies were of low methodological quality with a
      high potential for bias because none conducted a blinded outcome assessment. In
      addition, different criteria for the severity of bleeding events and different
      reference values of the laboratory tests were adopted. The low methodological
      quality limits the validity of the results of these studies. Some of the clinical
      queries proposed by the working group were not addressed by the studies available
      in the literature. The areas with evidence, although of low quality, are the
      following: general surgery in adults (for history, PT, APTT, platelet count and
      bleeding time), neurosurgery in adults (for history, PT, APTT, platelet count),
      adenotonsillectomy in children (for history, PT, APTT, platelet count and
      bleeding time), invasive procedures in adults (for PT, APTT, platelet count),
      dental extractions (for the bleeding time only), cataract extraction (for
      platelet count). No studies are available in children for major surgery other
      than adenotonsillectomy, neurosurgery and invasive procedures.

PMID- 19740529
TI  - The immunohistochemical localization of the glycosphingolipid asialo-GM1 in the
      intestine of weaned piglets.
AB  - The duodenum, jejunum, ileum, cecum and colon of three male hybrid piglets, 4
      weeks old just after weaning, were investigated for the immunohistochemical
      localization of the asialoganglioside, GM1 (asialo-GM1). The study revealed
      various degrees of labelling for this acid glycosphingolipid in neural,
      epithelial and blood elements in all the gut segments. The immunolabelled neural
      structures, represented by ganglionic perikarya and nerve fibers, were
      distributed throughout the intestinal wall and showed quantitative variations in
      the various regions. In contrast the numerical evaluation of labelled epithelial
      cells was encountered only in the terminal jejunum and along the entire ileum,
      cecum and large intestine. In addition, a heterogeneous population of
      immunolabelled leukocytes was spread randomly in the lamina propria and submucosa
      of the entire intestine and did not show any apparent quantitative fluctuations
      between the different parts. The observations regarding the typical distribution
      patterns of the asialoganglioside GM1 in ganglionic perikarya and epithelial
      cells of weaned piglets are discussed in relation to their possible functional
      significance in the intestine and other mammalian organs.

PMID- 19740530
TI  - Cilia-like structures anchor the amphioxus notochord to its sheath.
AB  - Body stiffness is important during undulatory locomotion in fish. In amphioxus,
      the myosepta play an important role in transmission of muscular forces to the
      notochord. In order to define the specific supporting role of the notochord in
      amphioxus during locomotion, the ultrastructure of 10 adult amphioxus specimens
      was analyzed using transmission electron microscopy. Numerous cilia-like
      structures were found on the surface of each notochordal cell at the sites of
      their attachment to the notochordal sheath. Ultrastructurally, these structures
      consisted of the characteristic arrangement of peripheral and central
      microtubular doublets and were anchored to the inner layer of the notochordal
      sheath. Immunohistochemically, a positive reaction to applied dynein and beta
      tubulin antibodies characterized the area of the cilia-like structures. We
      propose that reduced back-and-forth movements of the cilia-like structures might
      contribute to the flow of the fluid content inside the notochord, thus modulating
      the stiffness of the amphioxus body during its undulatory locomotion.

PMID- 19740531
TI  - Validation of existing prognostic models in patients with early-stage cervical
      cancer.
AB  - OBJECTIVE: Models that predict survival and recurrence in patients with early
      stage cervical cancer are important tools in patient management. We validated 12
      existing prognostic models in an independent population of patients with early
      stage cervical cancer. MATERIALS AND METHODS: We searched the literature for
      prognostic models in patients with surgically treated early-stage cervical
      cancer. The prognostic performance of these models was assessed in a consecutive
      group of surgically treated patients with early-stage cervical cancer treated in
      our hospital between 1982 and 2004. The performance of the models was visually
      assessed with calibration plots, which display the relation between the predicted
      and observed survival. RESULTS: Twelve published prognostic models met the
      inclusion criteria. The models categorized the patients into two to four risk
      groups. Prognostic factors most frequently used in these models were depth of
      invasion, lymph node metastasis, vascu/vascular space involvement, and tumor
      size. The models were validated in 563 consecutive patients with early-stage
      cervical cancer. All of the models underestimated the recurrence-free survival or
      disease-specific survival in our patients. Only two models performed reasonably
      well in our population. The use of more than three prognostic categories in the
      models was not meaningful. CONCLUSION: In general, the models underestimated the
      survival. Only 2 of the 12 prognostic models for patients with early-stage
      cervical cancer were valid for the prediction of the recurrence-free or disease
      specific survival in our patient population.

PMID- 19740532
TI  - Postoperative intra-abdominal collections using a sodium hyaluronate
      carboxymethylcellulose (HA-CMC) barrier at the time of laparotomy for ovarian,
      fallopian tube, or primary peritoneal cancers.
AB  - OBJECTIVES: To determine whether HA-CMC was associated with the development of
      postoperative intra-abdominal collections in patients undergoing laparotomy for
      ovarian, fallopian tube, or primary peritoneal malignancies. METHODS: We
      retrospectively identified all laparotomies performed for these malignancies from
      March 1, 2005 to December 31, 2007. The use of HA-CMC was identified.
      Laparotomies for malignant bowel obstruction or repair of fistulae were excluded.
      Intra-abdominal collections, non-infected and infected, were defined as localized
      intraperitoneal fluid accumulations in the absence of re-accumulating ascites.
      All other complications were also captured. Appropriate statistical tests were
      applied using SPSS 15.0. RESULTS: We identified 219 laparotomies with HA-CMC and
      204 without HA-CMC. Upper abdominal resections were performed in 65/219 (30%) HA
      CMC cases compared to 39/204 (19%) cases without HA-CMC (P=0.01). The rates of
      large bowel and/or rectal resections were similar in both cohorts. Intra
      abdominal collections were seen in 18/219 (8.2%) HA-CMC cases compared to 5/204
      (2.5%) cases without HA-CMC (P=0.009). HA-CMC was independently associated with
      the diagnosis of a postoperative intra-abdominal collection (P=0.01). All but 2
      collections developed in patients undergoing debulking procedures. CONCLUSIONS:
      HA-CMC appears to be associated with a higher rate of postoperative intra
      abdominal collections. This seems to be greatest in patients who are undergoing a
      debulking procedure.

PMID- 19740533
TI  - Pulmonary hypertension in two patients treated with bevacizumab for recurrent
      ovarian cancer.

PMID- 19740535
TI  - A phase II study of sunitinib in patients with locally advanced or metastatic
      cervical carcinoma: NCIC CTG Trial IND.184.
AB  - OBJECTIVE: Vascular endothethial growth factor (VEGF) and stem cell factor (c
      KIT) signaling may play a role in the development and progression of cervical
      carcinoma. Sunitinib malate is an oral, multi-targeted tyrosine kinase inhibitor
      that inhibits receptors for VEGF, c-Kit and platelet-derived growth factor. This
      multi-centre phase II study was performed to evaluate the activity of sunitinib
      in women with locally advanced or metastatic cervical carcinoma who had received
      up to one prior line of chemotherapy for advanced disease. METHODS: Sunitinib, 50
      mg/day, was administered in 6-week cycles (4 weeks on followed by 2 weeks off
      treatment). The primary endpoint was the objective response rate. RESULTS:
      Sixteen (84%) of 19 patients enrolled had stable disease (median duration 4.4
      months, 2.3-17 months), but no objective response was observed. Median time to
      progression was 3.5 months (range, 2.7-7.0 months). Four patients had fistulae
      develop on study treatment and an additional patient developed a fistula 3.5
      months after discontinuation of therapy. All five patients had received either
      prior chemoradiation or radiation. CONCLUSIONS: A higher rate of fistula
      formation (26.3%) was observed than would be expected and is of concern.
      Sunitinib has insufficient activity as a single agent in cervical cancer to
      warrant further investigation.

PMID- 19740536
TI  - Artificial insemination of captive European brown hares (Lepus europaeus PALLAS,
      1778) with fresh and cryopreserved semen derived from free-ranging males.
AB  - This study aimed to establish artificial insemination (AI) protocols to
      predictably initiate pregnancy during the breeding season in the European brown
      hare (EBH) (Lepus europaeus PALLAS, 1778). Semen was collected from seven captive
      and eight free-ranging males by means of electroejaculation. Semen from the free
      ranging males was cryopreserved using directional freezing. Total
      motility/integrity of fresh and frozen-thawed semen was 91.6%/87.7% and
      46.9%/53.8%, respectively. Ovulation was induced in ultrasonographically
      preselected females using a gonadotropin-releasing hormone analogue. Each female
      was inseminated with 1 mL fresh (Group A, n=16) or frozen-thawed semen (Group B,
      n=9) at a concentration of 100x10(6) spermatozoa/mL. The use of ultrasonography
      (10 to 22 MHz) confirmed the intracervical semen deposit, the success of
      artificial ovulation induction (formation of postovulatory corpus luteum), and
      permitted the monitoring of individual pregnancies. Although sperm
      motility/integrity was significantly different between groups, no significant
      difference was detected in conception rates (A, 87.50%; B, 77.78%). Because of
      embryonic resorption, there was a slight difference in fertility rate between
      groups (A, 62.5%; B, 77.78%). Overall, AI in captive EBH using fresh and frozen
      thawed semen achieved successful fertility rates. Long-term cryopreserved semen
      was used to bring new genetic material from the wild into a genetically limited
      captive population without extensive animal transport. Therefore, AI has the
      potential to enhance breeding programs for EBH especially when cryopreserved
      semen from wild donors is used.

PMID- 19740537
TI  - Evaluating the link between self-esteem and temperament in Mexican origin early
      adolescents.
AB  - The present study examined the relation between self-esteem and temperament in a
      sample of 646 Mexican-American early adolescents (mean age=10.4). Findings show
      that (a) early adolescents with high self-esteem exhibit higher levels of
      Effortful Control but, contrary to findings in adult samples, do not differ from
      low self-esteem adolescents in Negative Affectivity; (b) low self-esteem is
      associated with Depression; and (c) low self-esteem is associated with
      Aggression. These findings replicated for boys and girls, two measures of self
      esteem, and child and mother reports of temperament. The present study
      contributes to an emerging understanding of the link between self-esteem and
      temperament, and provides much needed data on the nature of self-esteem in ethnic
      minority populations.

PMID- 19740538
TI  - Concentrations and determinants of outdoor, indoor and personal nitrogen dioxide
      in pregnant women from two Spanish birth cohorts.
AB  - Determinants of outdoor, indoor and personal concentrations of nitrogen dioxide
      (NO(2)) were assessed in a subset of pregnant women of the Spanish INMA
      (Environment and Childhood) Study. Home indoor and outdoor NO(2) concentrations
      were measured during 48 h with passive samplers for 50 and 58 women from the INMA
      cohorts of Valencia and Sabadell, respectively. Women from Sabadell also carried
      personal NO(2) samplers during the same period. Data on time-activity patterns,
      socio-economic characteristics, and environmental exposures were obtained through
      questionnaires. Multiple linear regression models were developed to predict NO(2)
      levels. In Valencia, median outdoor NO(2) levels (42 microg/m(3)) were higher
      than median indoor levels (36 microg/m(3)). In Sabadell, personal NO(2) showed
      the highest median levels (40 microg/m(3)), followed by indoor (32 microg/m(3))
      and outdoor (29 microg/m(3)) levels. Personal exposure to NO(2) correlated best
      with the indoor NO(2) levels. Temporal and traffic-related variables were
      significant predictors for outdoor NO(2) levels. Thirty-two percent of the indoor
      NO(2) variability in the two cohorts was explained by outdoor NO(2) levels and
      the use of the gas appliances. The model for personal exposure accounted for 59%
      of the variance in NO(2) levels in Sabadell with four predictor variables
      (outdoor and indoor NO(2) levels, time spent in outdoor environments and time
      exposed to a gas cooker). No significant association was found between personal
      or indoor NO(2) levels and exposure to environmental tobacco smoke (ETS) at home.
      Personal NO(2) levels were found to be strongly influenced by indoor NO(2)
      concentrations. The study supports the use of time-activity patterns along with
      indoor measurements to predict personal exposure to traffic-related air
      pollution.

PMID- 19740539
TI  - Deletion of putative intronic control sequences does not alter cell or stage
      specific expression of Cr2.
AB  - The expression of the mouse Cr2 gene has been shown to be restricted to mature B
      cells, follicular dendritic cells and, in some reports, to a minor population of
      activated T cells. In this report, we demonstrate that the expression of
      antigen(s) recognized by the anti-CR2 antibody on the surface of T cells is co
      incident with T cell apoptotic death. Two distinct regions of the Cr2 gene have
      been implicated as critical for specific expression, the promoter region at the
      transcription start site and a control region within the first intron of the
      gene, approximately 1500 bp from the transcription start site. We have created a
      mouse that is lacking this intronic control sequence which, in the wild type (WT)
      mouse, contains multiple known binding sites for RBP-jkappa, Oct, NFAT and YY1
      proteins. The analysis of this mouse named Cr2iDelta (Cr2 intron deletion)
      demonstrated normal tissue specific expression of the Cr2 gene including a lack
      of expression in mouse T cells. B cell expression of the Cr2 gene products, CR1
      and CR2, is normal compared to WT, and the FDC of these mice continue to express
      Cr2 gene products. Therefore the intronic control region of the Cr2 gene, defined
      in transfection-based reporter gene assays as instrumental in controlling the
      cell specific expression profile of Cr2, does not influence the expression of the
      Cr2 gene in vivo nor alter the relative production of the CR1 and CR2 proteins
      via alternative slicing of Cr2 gene products.

PMID- 19740540
TI  - Aluminum hydroxide injections lead to motor deficits and motor neuron
      degeneration.
AB  - Gulf War Syndrome is a multi-system disorder afflicting many veterans of Western
      armies in the 1990-1991 Gulf War. A number of those afflicted may show
      neurological deficits including various cognitive dysfunctions and motor neuron
      disease, the latter expression virtually indistinguishable from classical
      amyotrophic lateral sclerosis (ALS) except for the age of onset. This ALS
      "cluster" represents the second such ALS cluster described in the literature to
      date. Possible causes of GWS include several of the adjuvants in the anthrax
      vaccine and others. The most likely culprit appears to be aluminum hydroxide. In
      an initial series of experiments, we examined the potential toxicity of aluminum
      hydroxide in male, outbred CD-1 mice injected subcutaneously in two equivalent-to
      human doses. After sacrifice, spinal cord and motor cortex samples were examined
      by immunohistochemistry. Aluminum-treated mice showed significantly increased
      apoptosis of motor neurons and increases in reactive astrocytes and microglial
      proliferation within the spinal cord and cortex. Morin stain detected the
      presence of aluminum in the cytoplasm of motor neurons with some neurons also
      testing positive for the presence of hyper-phosphorylated tau protein, a
      pathological hallmark of various neurological diseases, including Alzheimer's
      disease and frontotemporal dementia. A second series of experiments was conducted
      on mice injected with six doses of aluminum hydroxide. Behavioural analyses in
      these mice revealed significant impairments in a number of motor functions as
      well as diminished spatial memory capacity. The demonstrated neurotoxicity of
      aluminum hydroxide and its relative ubiquity as an adjuvant suggest that greater
      scrutiny by the scientific community is warranted.

PMID- 19740542
TI  - Problems and progresses in speciation of Al in human serum: an overview.
AB  - Aluminium (Al) is associated with many clinical disorders in renal patients. Al
      accumulation in brain has also been related to the neurodegenerative processes in
      Alzheimer's disease. In order to better understand Al transport in the human
      body, it is necessary to identify and quantify chemical species in which Al is
      present in body fluids and tissues. Among a variety of biological samples, Al
      speciation was the most frequently investigated in human serum. Improvements were
      made in the development of analytical techniques for the determination of the
      amount and composition of high molecular mass Al (HMM-Al) and low molecular mass
      Al (LMM-Al) species in human serum. However, due to the complex chemistry of Al
      in serum, its low total concentration and the high risk of contamination,
      speciation of Al in biological samples is still a difficult task for analytical
      chemists. In this work, problems related to speciation of Al in human serum are
      critically discussed. An overview of the progress that was made by the use of
      different analytical procedures, in order to propose analytical protocols for
      reliable speciation of Al in serum at low ng mL(-1) concentration range, is
      presented.

PMID- 19740541
TI  - Therapeutic potential of BAK gene silencing in aluminum induced neural cell
      degeneration.
AB  - Previous studies have demonstrated robust BAK gene silencing via RNA interference
      (RNAi). To investigate whether BAK RNAi may serve as a co-therapeutic agent in
      neural cell death, we herein established a cell degeneration model using a human
      neuroblastoma cell line (SH-SY5Y) treated by aluminum (Al). Combining cell
      viability assays and expression analyses by QRT (quantitative real-time)-PCR and
      immunocytochemistry, we selected and validated the optimal small interfering RNA
      (siRNA) from three candidate siRNAs for the BAK gene. Our data identified siRNA1
      as the most effective siRNA; the optimal concentration of the transfection agent
      was 10nM and the optimal incubation period was 24h. The transfection and
      knockdown efficiency was 93% and 58%, respectively, which closely correlated with
      the BAK protein expression. SH-SY5Y cells with BAK knockdown showed a clear
      resistance against cell death and Al-induced apoptosis. These results indicate
      that genetic inactivation of BAK could be an effective strategy in delaying the
      onset of apoptosis in Al-treated cells, and exemplify the therapeutic potential
      of RNAi-based methods for the treatment of neural cell degeneration.

PMID- 19740543
TI  - Effect of phosphate on aluminium-inhibited growth and signal transduction
      pathways in Coffea arabica suspension cells.
AB  - In acid soils, aluminium (Al) toxicity and phosphate (Pi) deficiency are the most
      significant constraints on plant growth. Al inhibits cell growth and disrupts
      signal transduction processes, thus interfering with metabolism of phospholipase
      C (PLC), an enzyme involved in second messenger production in the cell. Using a
      Coffea arabica suspension cell model, we demonstrate that cell growth inhibition
      by Al toxicity is mitigated at a high Pi concentration. Aluminium-induced cell
      growth inhibition may be due to culture medium Pi deficiency, since Pi forms
      complexes with Al, reducing Pi availability to cells. Phosphate does not mitigate
      inhibition of PLC activity by Al toxicity. Other enzymes of the phosphoinositide
      signal transduction pathway were also evaluated. Aluminium disrupts production of
      second messengers such as inositol 1,4,5-trisphosphate (IP(3)) and phosphatidic
      acid (PA) by blocking PLC activity; however, phospholipase D (PLD) and
      diacylglycerol kinase (DGK) activities are stimulated by Al, a response probably
      aimed at counteracting Al effects on PA formation. Phosphate deprivation also
      induces PLC and DGK activity. These results suggest that Al-induced cell growth
      inhibition is not linked to PLC activity inhibition.

PMID- 19740544
TI  - Noninvasive measurement of aluminium in human bone: preliminary human study and
      improved system performance.
AB  - Aluminium has been measured in the hands of 18 referent subjects and six
      aluminium welders using the technique of in vivo neutron activation analysis. The
      minimal detection limit (MDL) in the human subjects was 28.0 microgAl/gCa,
      whereas it was 19.5 microgAl/gCa in calibration standards. On average the
      aluminium exposed subjects had higher levels of aluminium in their hands than did
      the referent subjects. However, this difference only just achieved significance
      at the 5% level and should be treated with caution, since the study had not been
      deliberately designed to assess this difference. Following the preliminary human
      study, improvements were made to the measurement system with respect to the gamma
      ray detector array and to the timing sequence of irradiation-transfer-counting.
      These improvements were tested on the calibration standards, lowering the MDL
      from 19.5 microgAl/gCa to 8.32 microgAl/gCa. A similar improvement in human
      measurements would result in an in vivo MDL of 12.0 microgAl/gCa.

PMID- 19740545
TI  - Constitutive and aluminium-induced patterns of phenolic compounds in two maize
      varieties differing in aluminium tolerance.
AB  - Aluminium tolerance in maize is mainly due to more efficient Al exclusion.
      Nonetheless, even in tolerant varieties Al can gain access into the cells.
      Detoxification by binding to strong organic ligands should therefore play a role
      also in plants with high Al exclusion capacity. To test this hypothesis in this
      study the concentrations of soluble, free and bound, phenolics were analyzed in
      roots of two maize varieties differing in Al tolerance. Exposure for 24 h to 50
      microM Al in nutrient solution strongly inhibited root elongation in the
      sensitive variety 16 x 36, but not in the Al-tolerant variety Cateto. Cateto
      accumulated about half the concentration of Al in roots than 16 x 36 (analysis
      performed after root desorption with citrate). Roots of Al-tolerant Cateto
      contained higher concentrations of caffeic acid, catechol and catechin than roots
      of the sensitive variety. Exposure to Al induced the accumulation of taxifolin in
      roots of both varieties. However, Al-tolerant Cateto accumulated about twice the
      concentration than Al-sensitive 16 x 36 of this pentahydroxyfavonol. The molar
      ratio for phenolics with catecholate groups to Al was about unity in roots of
      Cateto, while in those of 16 x 36 the ratio was ten times lower. Both the fact
      that these phenolics are strong ligands for Al and their high antioxidant and
      antiradical activity suggest that these compounds may provide protection against
      the Al fraction that is able to surpass the exclusion mechanisms operating in the
      tolerant maize variety.

PMID- 19740546
TI  - Olanzapine vs. lithium in management of acute mania.
AB  - OBJECTIVE: Among the available mood stabilizers, it appears that lithium may
      share an important role for treatment of acute mania. In a study from Sep. 2007
      to Apr. 2008 at Razi Psychiatric Hospital we evaluated the efficiency of
      olanzapine vs. lithium. METHODS: Forty (40) female inpatients meeting DSM-IV-TR
      criteria for acute mania were entered into a 3-week parallel group, double-blind
      study for random assignment to olanzapine or lithium carbonate in a 1:1 ratio.
      Primary outcome measurements were the changes in Manic State Rating Scale (MSRS)
      at baseline and weekly intervals up to the third week. Similarly, overall illness
      severity was rated using the Clinical Global Impression-Severity of illness scale
      (CGI-S) at baseline and at the end of the third week. Analysis of the data was
      accomplished by means of split-plot (mixed) and repeated measures analysis of
      variance (ANOVA) and t test. RESULTS: While both olanzapine and lithium were
      found to be significantly helpful in the improvement of manic symptoms (p<0.05),
      lithium was considerably more successful by the end of the third week (p<0.0002
      and p<0.003, for frequency and intensity of the symptoms). CGI-S also showed
      important improvements with both olanzapine and lithium (p<0.043 and p<0.015 for
      olanzapine and lithium). CONCLUSION: Though both olanzapine and lithium were
      effective in the improvement of manic symptoms, lithium was more beneficial.

PMID- 19740547
TI  - Impact of depression heterogeneity on attention: an auditory oddball event
      related potential study.
AB  - BACKGROUND: Major depressive disorder is associated with a reduced ability to
      attend and concentrate, however, the extent to which attentional impairment is
      dependent on subtype remains to be clarified. METHODS: Event-related potentials
      (ERPs) associated with a well-validated auditory oddball, selective attention
      task, were recorded to determine the impact of melancholia (n=57) versus non
      melancholia (n=48) relative to controls (n=116). RESULTS: The key findings were
      an exaggeration of the P200 to both non-target and target stimuli and a reduction
      in the P300 to targets in patients with melancholia, relative to patients with
      non-melancholia and controls. In addition, the N200/P300 complex was slowed in
      latency corresponding to the slowed behavioural responses to targets in
      melancholia. Stepwise regression analysis also revealed that depression severity,
      but not psychomotor slowing, contributed to increases in P200 amplitude.
      LIMITATIONS: This study is cross-sectional and cannot determine whether the
      observed ERP changes are a state or trait marker, highlighting the need for a
      longitudinal study of ERP characteristics in different subgroups of depressed
      patients. CONCLUSIONS: Results point to a difficulty in differentiating
      significant stimuli in the environment in the depressed individual. The combined
      disruption of early sensory processing (P200) and subsequent context processing
      (N200/P300 complex) may provide a potential mechanism for the attentional
      impairment that is frequently observed in depression, particularly in more severe
      depression.

PMID- 19740548
TI  - Web-survey of pharmacological and non-pharmacological sleep interventions for
      children with early-onset bipolar spectrum disorders.
AB  - BACKGROUND: A web-based survey was developed to explore the effect of
      pharmacological and non-pharmacological interventions for sleep difficulties
      associated with Early-Onset Bipolar Spectrum Disorders (EBSD). METHOD: Four
      hundred ninety four parents of 4-12 year-olds, identified by parents as being
      diagnosed with EBSD, provided information about which professionals were
      consulted regarding their child's EBSD-sleep problems and pharmacological and non
      pharmacological interventions that helped or worsened sleep. RESULTS: Most
      parents reported consulting at least one medical, mental health, and/or school
      professional regarding their child's sleep problems. Psychiatrists and other
      physicians were most often consulted. The majority of parents reported several
      medications/supplements as helpful, most commonly, atypical antipsychotics
      (54.4%). Over half identified various pharmacological agents that worsened sleep,
      most commonly, stimulants (35.0%). Most parents also reported several non
      pharmacological interventions that aided sleep problems, most frequently, a sleep
      routine. Over two-thirds reported a variety of non-pharmacological interventions
      that worsened sleep, most notably, punishment (34.8%). LIMITATIONS: The sample
      was non-random consisting of self-selected and web-savvy parents who self
      identified their children as having EBSD and provided only parent derived data.
      CONCLUSIONS: Although exploratory and despite limitations, this is the first
      survey to report data on both pharmacological and non-pharmacological treatments
      for EBSD-sleep problems. It highlights clinical interventions that may improve or
      worsen EBSD-sleep and provides directions for future research.

PMID- 19740549
TI  - Childhood sexual abuse and hypothalamus-pituitary-thyroid axis in postpartum
      major depression.
AB  - OBJECTIVE: The aim of this study was to investigate the association between early
      life events in women with postpartum major depression and concomitant
      hypothalamus-pituitary-thyroid axis disturbances (HPTD), thyroid dysfunction or
      presence of thyroid antibodies. METHODS: Serum total tri-iodothyronine (TT3),
      free thyroxin (FT4), Thyroid-stimulating hormone (TSH), Thyroperoxidasa (TPOAb)
      and Thyroglobulin (TGAb) autoantibodies was measured in 103 major postpartum
      depressive women. HPTD was defined as TSH and/or T4 abnormal, presence of thyroid
      autoantibodies and alterations of TT3. All women were assessed with a psychiatry
      structured interview for DSM-IV. Early Trauma Inventory Self Report,
      sociodemographic, reproductive, psychosocial and psychopathological variables
      were also assessed. RESULTS: Sixty three percent of women had suffered childhood
      trauma, which was childhood sexual abuse in 27.2%. Childhood sexual abuse in
      postpartum major depression women increased the risk for thyroid dysfunction
      (OR=5.018, 95%CI=1.128-22.327), presence of thyroid autoantibodies (OR=2.528;
      95%CI=1.00-6.39) and HPTD (OR=2.955; 95%CI=1.191-7.32). Moreover, age over 34
      (OR=12.394; 95%CI=1.424-107.910) and previous postpartum depression (OR=8.470;
      95%CI=1.20-59.43) increased the risk for thyroid dysfunction in postpartum
      depression. LIMITATIONS: The study design does not allow us to know the direction
      of the association and there is a lack of previous assessment of current
      posttraumatic stress disorder. CONCLUSIONS: According to the present findings,
      childhood sexual abuse may represent an important risk factor for the presence of
      thyroid autoantibodies and HPTD in women with postpartum depression.

PMID- 19740550
TI  - Computer-aided neurocognitive remediation as an enhancing strategy for
      schizophrenia rehabilitation.
AB  - Cognitive dysfunction is a chronically disabling feature of schizophrenia,
      associated with limits in obtaining rehabilitation improvements. The purpose of
      this study is to assess the effectiveness of intensive computer-aided cognitive
      remediation treatment (CRT) added to a standard rehabilitation treatment (SRT),
      in enhancing neuropsychological performances and daily functioning in patients
      with schizophrenia. A 12-week, randomized, controlled, single-blind trial of
      neurocognitive remediation was carried out on 86 patients with clinically
      stabilized DSM-IV schizophrenia. Patients were assessed on cognitive and daily
      functioning before and after either CRT or placebo training that had been added
      to their SRT. After 3 months the repeated measure ANOVA showed a significant time
      x treatment interaction for executive function and attention performances and in
      daily functioning assessment in favour of patients in the SRT+CRT treatment.
      Results confirmed that cognitive remediation added to the SRT of schizophrenia
      enhanced its neuropsychological effects and increased the effects of a long-term
      rehabilitation programme in terms of functional outcomes.

PMID- 19740551
TI  - Positive schizotypy scores correlate with left visual field interference for
      negatively valenced emotional words: A lateralized emotional Stroop study.
AB  - Fourteen men scoring high and 14 men scoring low on a positive schizotypy scale
      participated in a lateralized emotional Stroop task. Vocal reaction times for
      color naming of neutral, positive and negative emotional words were recorded.
      Across participants, the color naming of neutral and emotional words was slightly
      faster to right than to left visual field presentations. In men with high scores
      on positive schizotypy, the presentation of negative words to the left visual
      field (right hemisphere) resulted in significant affective interference with
      color naming, which was significantly larger than in men with low scores.
      Correlational analysis also showed that positive schizotypy was significantly
      associated with emotional interference in response to LVF negative words. The
      outcome is discussed in terms of right hemispheric engagement in negative
      emotions in high positive schizotypic men.

PMID- 19740552
TI  - Activation of nuclear factor-kappaB in dogs with chronic enteropathies.
AB  - Homeostasis in the intestinal microenvironment between the immune system and
      luminal antigens appears disturbed in chronic enteropathies. Pro-inflammatory
      cytokines likely play a role in the pathogenesis of intestinal inflammation.
      Several inflammatory and immunoregulatory genes have associated nuclear factor
      kappaB (NF-kappaB) binding sites, which allow NF-kappaB to regulate gene
      transcription. The purpose of this study was to investigate (1) the occurrence of
      NF-kappaB activation during mucosal inflammation in situ, (2) the mucosal
      distribution pattern of cells expressing activated NF-kappaB within treatment
      groups, and (3) the effect of specific therapy on NF-kappaB activation. Dogs with
      chronic enteropathy were studied (n=26) and compared with 13 healthy dogs. Ten
      dogs had food responsive disease (FRD) and 16 had inflammatory bowel disease
      (IBD). NF-kappaB activation was detected in duodenal mucosal biopsies using a
      mouse monoclonal antibody (MAB 3026) that selectively binds the nuclear
      localization sequence of activated NF-kappaB. To identify macrophages, biopsies
      were stained using the MAC 387 antibody. Macrophages in the lamina propria double
      stained for MAC 387 and NF-kappaB were quantitated; epithelial cell expression of
      activated NF-kappaB was determined semi-quantitatively. Results showed that more
      macrophages positive for activated NF-kappaB were present in lamina propria of
      dogs with chronic enteropathy compared to control dogs (p<0.01). More NF-kappaB
      positive epithelial cells were observed in FRD dogs compared to IBD dogs
      (p<0.05). After therapy, the number of macrophages and epithelial cells staining
      positive for activated NF-kappaB decreased (p<0.01) in chronic enteropathy dogs.
      In conclusion, activation of NF-kappaB is closely associated with the
      pathophysiology of canine chronic enteropathy. Down-regulation follows successful
      therapy.

PMID- 19740553
TI  - Structure and sequence variation of the canine perforin gene.
AB  - Lymphocyte-mediated cytotoxicity is essential to control viral infections, limit
      lymphocyte expansion and activation, and survey for malignant cells. Humans with
      defects in lymphocyte cytotoxicity have reduced perforin function resulting in
      uncontrolled lymphocyte expansion, leading to excessive histiocyte activation and
      a hemophagocytic disorder. Dog breeds such as Bernese mountain dogs (BMD) have a
      high incidence of reactive and malignant diseases affecting histiocytes. This
      study addressed the hypothesis that changes in the perforin gene contribute to
      the development of hemophagocytic histiocytic sarcoma (HHS) in BMD. Canine
      perforin DNA was amplified and sequenced through multiple PCR assays from healthy
      and diseased dogs, and the gene structure determined by rapid amplification of
      cDNA ends. The coding component of the gene consists of 1679bp, with two exons of
      536bp and 1143bp separated by an intron of 865bp. Gene configuration and location
      differ from that in other species although the coding sequence is highly
      conserved. Three silent single nucleotide polymorphisms (SNP) were identified.
      Analysis of their distribution indicated a consistent genotype among 6 middle
      aged to older BMD without histiocytic diseases. Among samples from 10 dogs with
      HHS and 10 without histiocytic diseases SNP occurred with variable frequency. It
      was concluded that changes in the amino acid sequence of perforin were not
      associated with HHS but that a constellation of SNP may characterize BMD without
      histiocytic disease. Investigation of more dogs is required to confirm a specific
      genotype. Future studies should focus on the potential contribution of reduced
      perforin expression and/or function to HHS in dogs.

PMID- 19740554
TI  - Partial adenoidectomy by suction diathermy in children with cleft palate, to
      avoid velopharyngeal insufficiency.
AB  - OBJECTIVES: Adenoidectomy is indicated for the relief of paediatric nasal
      obstruction, sleep-disordered breathing and otitis media with effusion (OME).
      Velopharyngeal insufficiency (VPI) is a rare complication. The main risk factor
      is the presence of pre-existing velopharyngeal closure-impaired mechanisms,
      including submucosal or overt cleft palate. Despite possible benefits,
      adenoidectomy is frequently withheld in such children to avoid VPI. This study
      aims to demonstrate the efficacy and safety of partial adenoidectomy using
      suction diathermy in children who previously underwent overt cleft palate repair
      during infancy, to allow selective resection of tissue and symptom resolution
      without producing VPI. METHODS: Since 1994, 18 patients with previously corrected
      overt cleft palate have undergone partial adenoidectomy at this centre, for the
      treatment of nasal obstruction or sleep-disordered breathing, with or without
      OME. Three had existing VPI following their cleft correction surgery. Selective
      resection of the adenoid was performed transorally under indirect vision, using a
      malleable suction coagulator. This allowed exposure of the posterior choanae,
      leaving the remaining adenoid bulk intact. RESULTS: Patients were followed up at
      4 weeks, and subsequently at regular intervals (total follow up 30-180 months,
      median 92 months), including perceptual speech assessment in all cases. All
      demonstrated symptomatic improvement with respect to the original indications for
      surgery. None developed worsening hypernasal speech or other features of VPI, and
      there were no cases of symptomatic adenoidal re-growth. CONCLUSIONS: Partial
      adenoidectomy, employing a variety of methods, has been used successfully in
      children with submucosal cleft palate. This study demonstrates the safe and
      effective use of suction diathermy to enable partial adenoidectomy in children
      who have previously undergone surgical correction of overt cleft palate, allowing
      symptom resolution without producing VPI.

PMID- 19740555
TI  - Association between serum copper, zinc and hospital admissions among care home
      residents.
AB  - Nutritional status is important in various health care settings, long-term care
      is no exception. The relationship between protein-energy malnutrition and
      clinical outcomes in care homes has been reported. However, little is known about
      the roles of trace elements in clinical outcomes of care home residents. In 2002,
      75 severely disabled care home residents (mean age: 77.7+/-8.2 years, 64.3%
      males) were enrolled for study. The status of protein-energy malnutrition at
      enrollment was as follows: 47.9% underweight (body mass index, BMI<20 kg/m(2)),
      15.5% hypoalbuminemia (serum albumin <3.5 mg/dl), and 29.6% hypocholesterolemia
      (serum total cholesterol <160 mg/dl), respectively. During the 6-month follow-up,
      anthropometric measurements (i.e., BMI and mid-arm circumferences) remained
      similar, but the biochemical markers of nutritional status (i.e., albumin, total
      cholesterol) were significantly deteriorated, and both serum zinc and copper were
      significantly increased. Compared with subjects without hospitalizations during
      the follow-up period, subjects ever hospitalized had significantly lower mean
      serum levels of albumin (3.6+/-0.3 mg/dl vs. 3.9+/-0.3 mg/dl, p=0.002), zinc
      (74.3+/-12.1 vs. 89.6+/-20.5 microg/dl, p=0.020), and higher serum levels of
      copper (110.6+/-14.1 vs. 95.2+/-21.1 microg/dl, p=0.023) at baseline screening.
      Adjusted for age, sex, and protein-energy malnutrition, baseline serum copper
      (odds ratio=OR=1.08, 95% CI=1.02-1.15, p=0.015) and zinc (OR=0.92, 95% CI=0.84
      1.00, p=0.053) were significant independent predictive factor for hospital
      admissions. In conclusion, adjusted for age, sex, and protein-energy
      malnutrition, serum levels of copper and zinc both were independent predictive
      factors for hospitalizations among care home residents. Further interventional
      study is needed to clarify the prognostic roles of serum copper and zinc among
      care home residents.

PMID- 19740556
TI  - Cardiac amyloidosis and Brugada-like ECG pattern.
AB  - The Brugada syndrome is an inherited channelopathy associated with a high
      propensity of ventricular tachyarrhythmias and sudden cardiac death in
      individuals with structurally normal hearts. Recent data are indicative of mild
      structural changes, mainly involving the right ventricle, in patients with
      Brugada syndrome. We present the case of a patient with cardiac amyloidosis due
      to multiple myeloma who presented with pre-syncopal episodes and intermittent
      Brugada-like ECG pattern.

PMID- 19740557
TI  - Safety and observer variability of cardiac magnetic resonance imaging combined
      with low-dose dobutamine stress-testing in patients with complex congenital heart
      disease.
AB  - BACKGROUND: In patients with complex congenital heart disease (CHD) abnormal
      ventricular stress responses have been reported with dobutamine stress
      cardiovascular magnetic resonance (DCMR). These abnormal stress responses are
      potential indicators of long-term outcome. However, safety and reproducibility of
      this technique has not been reported in a larger study. The aim of this study was
      to report our experiences regarding safety and intra-observer and inter-observer
      variability of low-dose DCMR in complex CHD. METHODS: In 91 patients, 110 low
      dose DCMR studies were performed with acquisition of a short axis set at rest,
      and during dobutamine administration (7.5 MUg/kg/min maximum). We assessed
      biventricular end-diastolic volumes, end-systolic volumes, stroke volumes,
      ejection fraction and ventricular mass. Intra- and inter-observer variability for
      all variables was assessed by calculating the coefficient of variation (%), i.e.
      the standard deviation of the difference divided by the mean of 2 measurements
      multiplied by 100%. RESULTS: In 3 patients minor side effects occurred (vertigo,
      headache, and bigeminy). Ten patients experienced an increase in heart rate of
      >150% from baseline, although well tolerated. For all variables, intra-observer
      variability was <10% at rest and during stress. At rest, inter-observer
      variability was 10.5% maximal. With stress-testing, only the variability of
      biventricular end-systolic volumes (ESV) exceeded 10%. CONCLUSIONS: In patients
      with complex CHD low-dose DCMR is feasible, and safe. Intra-observer variability
      is low for rest and stress measurements. Inter-observer variability of
      biventricular ESV is high with stress-testing. Whether this limits the potential
      usefulness of DCMR for risk assessment during follow-up has to be assessed.

PMID- 19740558
TI  - Detailed distribution of acute pulmonary thromboemboli: direct evidence for
      reduction of acquisition length and radiation dose for triple rule-out CT
      angiography.
AB  - PURPOSE: To reduce the redundant acquisition range and total radiation dose for
      planning appropriate "triple rule-out" CT angiography (CTA) for acute chest pain,
      we evaluated the detailed distribution of pulmonary thromboemboli (PTE) in
      subjects with acute PTE. MATERIALS AND METHODS: Retrospective review of CTA n 75
      subjects (48-females; 57 +/- 16 years) with proven acute PTE was performed to
      determine whether PTE was present solely above the aortic arch or below the
      heart. RESULTS: 77% had PTE in the right upper lobe but none had PTE that were
      solely located higher than the aortic arch; 73% had PTE in the right middle lobe;
      80% had PTE in the right lower lobe, but none had PTE that were solely located
      lower than the heart. 81% had PTE in the left upper lobe and 3% of them had PTE
      solely located higher than the aortic arch; both had PTE in the right upper,
      middle, and lower, and the left lower lobes. 75% had PTE in the left lower lobe,
      but none had PTE that were solely located lower than the heart. The acquisition
      length in limited CTPA in this population was reduced on average by 21.9%
      compared with full CTPA. CONCLUSIONS: In subjects with acute PTE, there were none
      whose PTE was located solely in the upper lobes which were higher than the aortic
      arch, nor solely in the lower lobes which were lower than the heart. A limited
      range triple rule-out CTA protocol would decrease effective doses approximately
      22% relative to full chest CTA and may help the physician find all PE present.

PMID- 19740559
TI  - Recurrent form of neurogenic stunned myocardium: is myocardial adrenergic
      receptor distribution a dynamic process?
AB  - Neurogenic stunned myocardium mediated by stress-induced catecholamine acute
      release is considered as the central causative mechanism of transient left
      ventricular dysfunction syndrome (TVLDS). Interindividual differences in both LV
      beta-adrenergic receptor density and sympathetic innervation were proposed to
      explain the atypical forms of TVLDS. Whether this distribution is independent of
      age or may vary during ageing still remains unclear. We report a recurrent form
      of TLVDS characterized by two different patterns. Whilst myocardial receptor
      distribution or sympathetic innervation appears to follow a dynamic process, the
      precise determinants of these variations remain largely unknown.

PMID- 19740560
TI  - Epidemiologic characteristics of bluetongue virus serotype 8 laboratory-confirmed
      outbreaks in The Netherlands in 2007 and a comparison with the situation in 2006.
AB  - A major epidemic of bluetongue virus serotype 8 (BTV-8) occurred in Western
      Europe in 2006. During 2007 it became evident that BTV-8 had survived the winter
      and a re-emerging epidemic quickly developed. The objective of this study was to
      describe the severity and clinical impact of the BTV-8 epidemic in 2007 in The
      Netherlands in laboratory-confirmed outbreaks and to compare this with the
      situation in 2006. The relative frequency of clinical signs in BTV-8 affected
      sheep flocks and cattle herds in 2007 and 2006 was similar. The most prominent
      changes were a higher proportion of sheep flocks with lameness and a much higher
      proportion of cattle herds reporting a decrease in milk yield in 2007. BTV-8
      associated morbidity and mortality incidence rates in sheep flocks and cattle
      herds were significantly (P<0.001) higher in 2007 than in 2006. Both in sheep
      flocks and cattle herds, BTV-8 associated case fatality was significantly
      (P<0.001) lower in 2007, which was probably due to better medical treatment of
      sick animals. There were significantly (P<0.001) more fertility problems
      associated with BTV-8 infection in outbreak cattle herds in 2007 compared to
      2006.

PMID- 19740561
TI  - Hitting the mark or falling short with nanotechnology regulation?
AB  - Regulation of all new technology ebbs and flows between periods of under- and
      over-regulation, often dependant on the viewpoint of the observer and the
      underlying objectives of the particular regulation. As illustrated by genetic
      modification (GM) applications, defining what constitutes appropriate regulation
      for a rapidly evolving technology can be difficult. Drawing upon the lessons of
      GM, we argue that nanotechnology will go through similar periods of inappropriate
      regulation. As with GM, future regulatory responses to nanotechnology will be
      shaped by perceptions of risk and willingness to accept varying levels of risk.
      With varying responses between jurisdictions appearing inevitable, we argue that
      the timing and type of regulation adopted for nanotechnology, and its
      appropriateness, will be crucial to its commercial success.

PMID- 19740562
TI  - Presence of lactic bacteria in the air of a winery during the vinification
      period.
AB  - In this paper we have studied the presence and evolution in the winery air of the
      lactic bacteria responsible for malolactic fermentation. Sampling took place
      during the winemaking process (between September 2007 and July 2008) in a winery
      from the Rioja appellation in Spain. The results obtained indicated that the
      presence of these microorganisms in the atmosphere was detected when grapes were
      entering the winery, while malolactic fermentation was taking place, and when
      liquid containing bacteria was manipulated. The species and clones of the lactic
      bacteria identified were also related to those present in the vinification tanks
      at any given stage of the process.

PMID- 19740563
TI  - A home environment test battery for status assessment in patients with advanced
      Parkinson's disease.
AB  - A test battery for assessing patient state in advanced Parkinson's disease,
      consisting of self-assessments and motor tests, was constructed and implemented
      on a hand computer with touch screen in a telemedicine setting. The aim of this
      work was to construct an assessment device, applicable during motor fluctuations
      in the patient's home environment. Selection of self-assessment questions was
      based on questions from an e-diary, previously used in a clinical trial. Both un
      cued and cued tapping tests and spiral drawing tests were designed for capturing
      upper limb stiffnes, slowness and involuntary movements. The patient interface
      gave an audible signal at scheduled response times and was locked otherwise. Data
      messages in an XML-format were sent from the hand unit to a central server for
      storage, processing and presentation. In tapping tests, speed and accuracy were
      calculated and in spiral tests, standard deviation of frequency filtered radial
      drawing velocity was calculated. An overall test score, combining repeated
      assessments of the different test items during a test period, was defined based
      on principal component analysis and linear regression. An evaluation with two
      pilot patients before and after receiving new types of treatments was performed.
      Compliance and usability was assessed in a clinical trial (65 patients with
      advanced Parkinson's disease) and correlations between different test items and
      internal consistency were investigated. The test battery could detect treatment
      effect in the two pilot patients, both in self-assessments, tapping tests'
      results and spiral scores. It had good patient compliance and acceptable
      usability according to nine nurses. Correlation analysis showed that tapping
      results provided different information as compared to diary responses. Internal
      consistency of the test battery was good and learning effects in the tapping
      tests were small.

PMID- 19740564
TI  - O(6)-Methylguanine-DNA methyltransferase expression and prognostic value in brain
      metastases of lung cancers.
AB  - O(6)-Methylguanine-DNA methyltransferase (MGMT) is critical for repairing pro
      mutagenic DNA bases and is correlated with response to alkylating agents in
      cancers. Since there is great interest in pursuing the potential role of
      temozolomide, a novel alkylating agent, in the treatment of brain metastases,
      this study aimed to evaluate MGMT expression as well as its prognostic value in
      this devastating disease. We studied the expression and methylation status of
      MGMT in 86 brain metastases of lung cancers. Twenty of them had matched primary
      lung tumor tissues available for direct comparison. MGMT expression was assessed
      by immunohistochemistry (IHC); the methylation status of MGMT promoter was
      analyzed by nested methylation-specific PCR (MSP) and validated by quantitative
      real-time PCR analysis. Positive nuclear MGMT expression was detected more
      frequently in brain metastases as compared with primary lung cancers (83% versus
      50%, P=0.004). The discordance in MGMT expression persisted in the 20 paired
      primary and metastatic tumors (P=0.031). MGMT promoter hypermethylation was
      highly correlated with loss of MGMT expression. Both univariate and multivariate
      analyses showed that median overall survival was significantly longer in patients
      with positive MGMT expression in brain metastases (16.5 versus 3.5 months,
      P<0.001). In conclusion, MGMT expression was enhanced in brain metastases as
      compared with the primary lung cancers. MGMT expression in brain metastases was
      significantly correlated with better survival.

PMID- 19740565
TI  - Phase I/II study of docetaxel and S-1, an oral fluorinated pyrimidine, for
      untreated advanced non-small cell lung cancer.
AB  - The purpose of this phase I/II study is to evaluate a new combination
      chemotherapy consisting of docetaxel and S-1 as front-line therapy for patients
      with untreated advanced non-small cell lung cancer (NSCLC). The treatment
      included docetaxel on day 1 and oral S-1 at a fixed dose of 40mg/m(2)
      administered twice daily on days 1-14 and repeated every 3 weeks. In phase I,
      docetaxel at escalating doses of 40 (level 0), 50 (level 1) and 60mg/m(2) (level
      2) was administered starting from level 1. Because only one patient among the 6
      patient cohort at level 1 and no patient among the 3-patient cohort at level 2
      experienced defined dose-limiting toxicity (DLT), level 2 was determined as the
      recommended dose. In phase II, 60 patients were treated at the recommended dose
      for median 3 cycles, and the overall response rate was 30% (95% confidence
      interval [CI], 18.9-43.2%), and the median overall and progression-free survival
      times were 15.2 (95% CI: 10.5-17.7) and 4.9 (95% CI: 3.5-5.6) months,
      respectively. The most frequent toxicities experienced were neutropenia, febrile
      neutropenia and appetite loss; all toxicities were however well manageable. The
      present regimen showed a potent activity with mild toxicity in untreated NSCLC.

PMID- 19740566
TI  - Reinventing species selection with molecular phylogenies.
AB  - Species selection as a potential driver of macroevolutionary trends has been
      relegated to a largely philosophical position in modern evolutionary biology.
      Fundamentally, species selection is the outcome of heritable differences in
      speciation and extinction rates among lineages when the causal basis of those
      rate differences can be decoupled from genotypic (within-population) fitnesses.
      Here, we discuss the rapidly growing literature on variation in species
      diversification rates as inferred from molecular phylogenies. We argue that
      modern studies of diversification rates demonstrate that species selection is an
      important process influencing both the evolution of biological diversity and
      distributions of phenotypic traits within higher taxa. Explicit recognition of
      multi-level selection refocuses our attention on the mechanisms by which traits
      influence speciation and extinction rates.

PMID- 19740567
TI  - Compositional homeostasis of the dinoflagellate Protoceratium reticulatum grown
      at three different pCO2.
AB  - In the CO2-richer world that awaits us, the impact of elevated pCO2 on the
      allocation of resources in phytoplankton may have profound repercussions on the
      physiology of the microalgae and on the ecology of the ecosystems of which they
      are part. We studied the overall physiology and cell composition of the
      potentially toxic dinoflagellate Protoceratium reticulatum subjected to a medium
      term increase of CO2. The physiological responses investigated were growth rates,
      cell size, photosynthetic and respiratory rates, and key enzyme activities. Cell
      composition was assessed by conventional analytical methods and FTIR
      spectroscopy. After 3 generations of incubation at current atmospheric, high and
      very high pCO2 (380, 1000, 5000ppm CO2), growth, photosynthesis, and dark
      respiration rates increased significantly, but the internal composition was only
      slightly affected. We propose the homeostasis of cell composition as a strategy
      that organisms can use to tackle environmental perturbations, especially when
      they are of relatively short duration.

PMID- 19740568
TI  - [Endoscopic argon plasma coagulation in recurrent tracheoesophageal fistula.
      Clinical series and review of the literature].
AB  - INTRODUCTION: Recurrent tracheoesophageal fistula (RTEF) is a complication that
      occurs in up to 15% of patients after esophageal atresia repair. The clinical
      features include coughing, aspiration, recurrent pneumonia and failure to thrive.
      Surgical treatment is recommended. However, since 1980, the endoscopic route has
      been used as a therapeutic alternative. Distinct techniques have been employed
      with an overall success rate of 63%. PURPOSE: To evaluate a new endoscopic
      treatment for RTEF with argon plasma coagulation (APC). METHODS: Six patients
      with RTEF treated with endoscopic APC between 2003 and 2007 at a single
      institution (Clinica Alemana, Santiago, Chile) were included. We also performed a
      systematic literature search. Nineteen articles were selected, with a total of 77
      patients treated through the endoscopic route. RESULTS: Treatment was successful
      in 66% of the patients with a follow-up of more than 12 months. On average, the
      patients required two applications of APC. This success rate was similar to that
      reported in published series. CONCLUSION: Endoscopic treatment with APC in RTEF
      seems to be useful and easily applied. Because of the complexity of surgical
      treatment, we recommend endoscopic treatment as the first approach in patients
      with RTEF.

PMID- 19740569
TI  - [Diagnostic yield in benign anal disease in primary care].

PMID- 19740570
TI  - [Chronic fatigue syndrome. Consensus document].

PMID- 19740572
TI  - [The "new flu": has the problem been approached properly?].

PMID- 19740574
TI  - Synthesis and anticancer activity of N-bis(trifluoromethyl)alkyl-N'-thiazolyl and
      N-bis(trifluoromethyl)alkyl-N'-benzothiazolyl ureas.
AB  - A number of N-bis(trifluoromethyl)alkyl-N'-thiazolyl and -benzothiazolyl ureas
      have been synthesized and evaluated for their in vitro antiproliferative
      activities against the human cancer cell lines at the National Cancer Institute
      (NCI, USA). The activity was shown for compounds 8a,c and 9a-c. The most
      sensitive cell lines relative to the tested compounds are: 8c PC-3 (prostate
      cancer, logGI(50) -7.10), 9c SNB-75 (CNS cancer, logGI(50) -5.84), 9b UO-31
      (renal cancer, logGI(50) -5.66), and SR (leukemia, logGI(50) -5.44) human cancer
      cells.

PMID- 19740573
TI  - [Designing a clinical microbiology laboratory].
AB  - The microbiology laboratory should be a safe, efficient, and comfortable place
      for those working there, and a pleasant place for visitors. According to the ISO
      15189 standard, it should be spacious enough for the workload to be carried out
      without jeopardizing quality or the safety of the persons present, whether
      workers or visitors, and provide optimal comfort to all occupants. In addition,
      the setup should respect the privacy of patients, and provide controlled access
      to the different laboratory areas and a safe place for storing clinical samples,
      manuals, and reagents. In the design of the facilities, the needs of specialists,
      technicians, and other personnel must converge, without forgetting patients,
      their relatives, and other visitors. The clinical microbiology laboratory has
      certain characteristics that make it different from other diagnostic
      laboratories. Its main activity involves isolation, propagation, and handling of
      pathogenic microorganisms that pose a risk to the laboratory personnel. To
      minimize this risk, the laboratory must meet a certain level of biosafety.
      Moreover, correct interpretation of microbiological cultures depends on the
      capacity of the laboratory to avoid or minimize the presence of contaminants;
      hence, proper handling of samples and cultures (aseptic conditions, biosafety
      cabinet) is mandatory. A number of documents and regulations, from very general
      to highly specific (biosafety), affect the design of the microbiology laboratory.
      The aim of this report is to establish the minimum requirements and
      recommendations for designing clinical microbiology laboratories, based on a
      review of current regulations. It is contemplated as an aid to microbiology
      specialists who are designing or planning to reform their laboratories.

PMID- 19740575
TI  - [Accessory spleens after splenectomy in a patient with common variable
      immunodeficiency].
AB  - INTRODUCTION: Blood cells are mainly destroyed in the spleen during autoimmune
      cytopenia. Amongst the various therapeutic strategies, splenectomy is sometimes
      necessary during the disease course. However, splenosis or accessory spleens can
      account for autoimmune cytopenia relapse after initial splenectomy in these
      patients. CASE REPORT: We report an 18-year-old male with common variable
      immunodeficiency who presented with immunological thrombocytopenia. Splenectomy
      allowed remission of cytopenia, but a relapse was attributed to splenosis,
      because Jolly bodies were absent on blood smear. Laparoscopic splenectomy of
      accessory spleens induced long term remission. A literature review is performed.
      CONCLUSION: Fifteen to 20% of relapses of autoimmune cytopenia treated by
      splenectomy are related to accessory spleens. Ablation of accessory spleens can
      cure again the patients, including patients with accompanying common variable
      immunodeficiency.

PMID- 19740576
TI  - [Antineutrophil cytoplasmic antibody associated vasculitis: an uncommon side
      effect of propylthiouracil].
AB  - INTRODUCTION: Agranulocytosis or allergic skin reactions are common side effects
      of antithyroid drugs. Antineutrophil cytoplasmic antibody (ANCA) associated
      vasculitis is very uncommon. CASE REPORT: We report a 29-year-old woman treated
      with propylthiouracil for Graves' disease who developed a vasculitic skin
      involvement. ANCA with antimyeloperoxidase specificity were documented. Symptoms
      resolved after discontinuation of the drug. CONCLUSION: ANCA associated
      vasculitis is an unusual complication of propylthiouracil. Prognosis is
      conditioned by renal and pulmonary involvement.

PMID- 19740577
TI  - [Lymphoma of the pituitary stalk].
AB  - INTRODUCTION: Tumors of the pituitary stalk are rare and their diagnosis is
      sometimes difficult. CASE REPORT: We report a case of a primary lymphoma of the
      pituitary stalk in a 78-year-old patient. To our knowledge, only seven similar
      cases have been previously published: prominent symptoms were headache, fatigue
      and diplopia; biologically, anterior pituitary low secretion or
      hyperprolactinemia were found in the majority of cases; regarding the imaging,
      only three patients presented an initial and isolated lesion of the stalk;
      histological evidence was obtained by a trans-sphenoidal biopsy in case of
      hypothalamic or pituitary associated lesion or by a trans-cranial biopsy in the
      event of an isolated lesion. As an alternative, a lumbar puncture could be
      performed; although less invasive, its diagnostic performance is lower.
      CONCLUSION: Current treatment relies on chemotherapy with intravenous
      methotrexate associated with intrathecal methotrexate infusion if cerebrospinal
      showed abnormal cells. Unfortunately, the results remain poor with a median
      survival of 9 months.

PMID- 19740578
TI  - [Macroenzymes: macro-ASAT and macro-CPK. Two cases and literature review].
AB  - INTRODUCTION: Macroenzymes are high molecular weight complex formed by the
      binding of one enzyme and a serum macromolecule, responsible for an increase in
      the activity of the corresponding enzyme in blood assay. CASE REPORTS: We report
      two cases: firstly, a macro-aspartate aminotransferase (macro-ASAT) discovered in
      an 82-year-old woman who presented with an isolated and persistent elevation of
      the ASAT activity that was discovered after sepsis, secondly, a macro-creatine
      kinase (macro-CPK) diagnosed in a 62-year-old man after several years of
      investigations for a persistent CPK elevation. These two case reports allowed us
      to discuss the mechanism leading to the formation of macroenzymes and the
      usefulness of their determination. Although macroenzymes are generally non
      pathologic, they may be associated with auto-immune, neoplastic or infectious
      diseases. CONCLUSION: The possibility of a macroenzyme should be entertained in
      the presence of an unexplained and isolated increased enzyme activity. It
      prevents costly and unnecessary investigations.

PMID- 19740579
TI  - [Mechanisms of pharmacokinetic drug-drug interactions].
AB  - Pharmacokinetic drug-drug interactions occur when a drug alters the disposition
      (absorption, distribution, elimination) of a coadministered agent.
      Pharmacokinetic interactions may result in the increase or the decrease of plasma
      drug concentrations. These modifications are variable in intensity but can lead
      to contraindications of the association. The mechanisms of pharmacokinetic
      interactions involve drug metabolizing enzymes, drug transporters and orphan
      nuclear receptors that regulate at the transcriptional level the expression of
      enzymes and transporters. The increase of drug plasma concentrations is generally
      related to the inhibition of enzymes and/or drug transport. The decrease of drug
      concentrations reflects the activation of orphan nuclear receptors by inducers
      that lead to the increase of the expression of enzymes and drug transporters.
      Inhibition of drug metabolism or transport is quite immediate (24-48h) while
      induction is a slower process (7-10 days). Complex situations may be observed
      with drugs that are both inducers and inhibitors (rifampin, ritonavir). They can
      cause the decrease and the increase of the exposure of the combined agent
      depending on the duration of the association.

PMID- 19740580
TI  - Comparison of two techniques of cinch suturing to avoid widening of the base of
      the nose after Le Fort I osteotomy.
AB  - All Le Fort I osteotomies have the potential to alter the dimensions of the alar
      base, and widen it. Surgical techniques to control this lateralisation of the
      base of the nose, including those of cinch suturing of the alar base, have been
      widely described and modified. We have compared two techniques of cinch suturing
      to try and prevent widening of the base of the nose after Le Fort I osteotomy. We
      studied 40 patients with skeletal class III facial deformities treated by
      orthognathic operations by the same surgeon. They were randomly divided into two
      groups of 20 each, one of which was treated with a classic cinch suture and the
      other by a modified technique. The distances between the nasofacial skinfold at
      the left alar bases, the columella, and the right nasofacial skinfold were
      recorded before and six months after operation. The results of the modified
      technique were more stable than those after classic suturing. In only 3/20
      patients in the classic group did the suture prevent nasal widening, whereas in
      the modified group the number was 14/20.

PMID- 19740582
TI  - How are macroinvertebrates of slow flowing lotic systems directly affected by
      suspended and deposited sediments?
AB  - The effects of suspended and deposited sediments on the macroinvertebrates are
      well documented in upland streams but not in slower flowing lowland rivers. Using
      species found in lowland lotic environments, we experimentally evaluate
      mechanisms for sediments to affect macroinvertebrates, and in one experiment
      whether salinity alters the effect of suspended sediments. Suspended kaolin clay
      reduced feeding of Ischnura heterosticta (Odonata: Coenagrionidae) at high
      turbidity (1000-1500 NTU) but had no effects on feeding of Hemianax papuensis
      (Odonata: Aeshnidae) and Micronecta australiensis (Hemiptera: Corixidae). In
      freshwater (0.1 mS/cm), survival of Ischnura aurora was poor in clear water, but
      improved with suspended kaolin. Growth and feeding of I. aurora were unaffected
      by suspended sediments and salinity. Burial (1-5 mm) of eggs with kaolin or sand
      reduced hatching in Physa acuta (Gastropoda: Physidae), Gyraulus tasmanica
      (Gastropoda: Planorbidae) and Chironomus cloacalis (Diptera: Chironomidae).
      Settling sediments may pose greater risk to lowland lotic invertebrates than
      suspended sediments.

PMID- 19740583
TI  - Geostatistics as a validation tool for setting ozone standards for durum wheat.
AB  - Which is the best standard for protecting plants from ozone? To answer this
      question, we must validate the standards by testing biological responses vs.
      ambient data in the field. A validation is missing for European and USA
      standards, because the networks for ozone, meteorology and plant responses are
      spatially independent. We proposed geostatistics as validation tool, and used
      durum wheat in central Italy as a test. The standards summarized ozone impact on
      yield better than hourly averages. Although USA criteria explained ozone-induced
      yield losses better than European criteria, USA legal level (75 ppb) protected
      only 39% of sites. European exposure-based standards protected > or =90%.
      Reducing the USA level to the Canadian 65 ppb or using W126 protected 91% and
      97%, respectively. For a no-threshold accumulated stomatal flux, 22 mmol m(-2)
      was suggested to protect 97% of sites. In a multiple regression, precipitation
      explained 22% and ozone explained <0.9% of yield variability.

PMID- 19740584
TI  - [Siliconoma mimicking pectoral tumor: About one case report].

PMID- 19740585
TI  - "Mouth to mouth ventilation": a comparison of the laryngeal mask airway with the
      Laerdal Pocket Facemask.
AB  - Ten nurses with basic airway management experience were formally trained to use a
      classic laryngeal mask airway (LMA) and a Laerdal Pocket Facemask (LPFM) for
      oxygen enriched expired air ventilation (EEAV). They then used both of these
      devices for EEAV in a randomised fashion in 100 anaesthetised ASA I/II patients
      for elective surgery. EEAV was considered successful if the patient's arterial
      oxygen saturation was maintained above 93% on room air for 3 min. EEAV success
      rates for the LMA and LPFM were 95% and 51% respectively (P=0.03). There was no
      apparent learning curve for either apparatus. Mean time in seconds (s) for first
      successful ventilation from picking up the apparatus was 26.8s and 15.1s, for the
      LMA and LPFM respectively (P<0.005). Although the LMA took significantly longer
      time to insert, it proved to be more successful and easier to use than the LPFM
      for EEAV.

PMID- 19740586
TI  - Delta-opioid receptor ligands in shock treatment.

PMID- 19740587
TI  - The higher the educational level of the first-time mother, the lower the fetal
      and post-neonatal but not the neonatal mortality in Belgium (Flanders).
AB  - OBJECTIVE: To assess, in a homogenous population of primiparous women, how fetal
      and infant (=first year of life) mortality varied by the mothers' level of
      education. STUDY DESIGN: We conducted an observational study in Flanders
      (Northern Belgium) involving 170,948 primiparous women who delivered in Flanders
      during the period 1999-2006, and their 174,495 babies. We linked the maternal
      education (3 levels) with a series of obstetrical and perinatal events, with
      special emphasis on fetal and infant death. A logistic regression analysis was
      performed to adjust for confounders. RESULTS: The incidence of fetal (0.21% -
      high level of education; 0.35% - medium level; 0.84% - low level) and infant
      mortality (0.32%; 0.41%; 0.70%, respectively), followed an inverse maternal
      educational gradient: higher with a lower level of education. However, neonatal
      death (0-27 days) was independent of the educational level of the mother. The age
      of the woman at delivery, the use of assisted reproductive technology and the
      incidence of twin birth increased while the rates of preterm birth (7.7% - high
      level; 8.9% - medium level; 10% - low level) and low birth weight (7.2%; 9.5%;
      11.8%, respectively) decreased with the mother's educational level. CONCLUSION:
      Perinatal and obstetrical outcome differ according to the level of the education
      of the mother, which is a determinant of the incidence of fetal and post-neonatal
      death but not of early and late neonatal death (0-27 days).

PMID- 19740588
TI  - Hysteroscopic evaluation of endocervical and endometrial lesions observed after
      different procedures of embryo transfer: a prospective comparative study.
AB  - OBJECTIVE: Endocervical and endometrial damage observed after different
      procedures of embryo transfer (ET) were investigated using diagnostic
      hysteroscopy. STUDY DESIGN: Prospective, descriptive and comparative study, in an
      Infertility centre, University Hospital. Hundred consecutive infertile patients
      with a normal uterine cavity, included in an IVF program, were enrolled between
      May 1st, 2006 and April 30th, 2007. All the patients had a diagnostic
      hysteroscopy immediately after trial ET using soft ET catheters: (i) IVF Sydney
      Set (Cook, Limerick, Ireland) (n=27), (ii) Elliocath (Ellios, Paris, France)
      (n=34), (iii) Frydman classic 4.5 (CCD, Paris, France) (n=19), and rigid ET
      catheters: Memory Frydman 4.5 (CCD, Paris, France) (n=20). All the procedures
      were recorded and blindly reviewed. Data were analyzed using a Kruskal-Wallis
      test for age and severity of endometrial lesions, or Fisher's exact test for
      binary criteria. RESULTS: Endocervical lesions were more frequently encountered
      in the soft (63%) and rigid (85%) Frydman's catheter groups compared to other
      groups (Elliocath: 29%, IVF Sydney Set: 26%; p<0.0001). Presence of blood on the
      catheter, and endometrial lesions were significantly less frequent in soft
      catheter groups compared to the rigid catheter group (p<0.0001). Severe
      endometrial lesions were less frequently observed when soft catheters were used
      (85%, 53%, 32%, 11% for Memory Frydman, Frydman classic, Elliocath and IVF Sydney
      Set, respectively; p<0.0001). The presence of blood on the catheter signed severe
      endometrial lesions. CONCLUSION: All ET catheters can lead to endocervical and
      endometrial damage. Severe endometrial lesions were less frequent when soft
      catheters were used.

PMID- 19740589
TI  - An efficient protocol for the detection of chromosomal abnormalities in
      spontaneous miscarriages or foetal deaths.
AB  - OBJECTIVE: Characterization of chromosomal abnormalities in 232 spontaneous
      miscarriages or foetal deaths using both classical and molecular cytogenetics.
      STUDY DESIGN: Chromosomal abnormalities are responsible for 40-50% of all early
      pregnancy losses. Conventional cytogenetics is associated with 10-40% of culture
      failure. Comparative genomic hybridization (CGH) is a DNA-based technique that
      screens chromosome imbalances in the whole genome and may overcome this problem,
      although additional methods are required to distinguish between different
      ploidies, mosaicisms and maternal cell contamination. For a full characterization
      of chromosomal aberrations in 232 spontaneous miscarriages or foetal deaths we
      applied a sequential protocol that uses conventional cytogenetics, plus CGH and
      touch fluorescence in situ hybridization (Touch FISH). RESULTS: Successful
      karyotyping was obtained in 173/232 (74.6%) of the cases, 66/173 (38.2%) of which
      had an abnormal chromosomal complement. CGH and Touch FISH analyses revealed
      another 19 abnormal cases in the 63 failures of culture. Overall there were
      85/233 (36.6%) cases with an abnormal chromosomal complement, with examples from
      all three trimesters. Comparing cases, with or without chromosomal abnormalities,
      no statistical differences were found between women with one or recurrent
      miscarriages. On the contrary, significant differences were found comparing mean
      maternal ages or mean gestational ages, in cases with or without chromosomes
      abnormalities. CONCLUSION: Adopting this sequential protocol, chromosomal
      complement information was available even in cases with culture failure.

PMID- 19740590
TI  - Maternal pro-hepcidin at term correlates with cord blood pro-hepcidin at birth.
AB  - OBJECTIVE: Hepcidin, a small 25 amino-acid antimicrobial peptide, has a
      significant role in the regulation of iron homeostasis. Pro-hepcidin, an 84 amino
      acid peptide, is a precursor of the active hepcidin. The main aim of this study
      was to examine the association of maternal serum pro-hepcidin with cord blood pro
      hepcidin levels in term pregnancies, and whether maternal and newborn iron status
      measurements correlate with the pro-hepcidin level. STUDY DESIGN: The population
      consisted of 193 pregnant women admitted to the Kuopio University Hospital
      (Finland) for delivery, and their full-term newborn infants (cord blood). The
      main outcome measures were serum pro-hepcidin (ELISA), blood count including red
      cell indices, serum iron status markers (including iron, transferrin, transferrin
      saturation (TfSat), transferrin receptor (TfR) and ferritin), birth weight and
      placental weight and relative placental size. A Mann-Whitney U-test and
      Spearman's correlation were used to test the associations between the parameters.
      RESULTS: Pregnant women had higher pro-hepcidin level than their newborns (325
      microg/L vs. 235 microg/L, p<0.001). The Spearman's correlation between the
      maternal and cord blood serum pro-hepcidin level was highly significant
      (correlation coefficient 0.600, p<0.001). Additionally, both maternal and cord
      blood pro-hepcidin levels correlated weakly but significantly with placental
      weight and relative placental size. However, pro-hepcidin level did not correlate
      with iron status measurements in pregnant women or in their newborns.
      CONCLUSIONS: The present results suggest that pro-hepcidin is not associated with
      maternal or newborn iron homeostasis at term and birth, but may act in concert
      with the placenta, as evidenced by the correlation between maternal and fetal pro
      hepcidin levels and their slight correlation with placental weight.

PMID- 19740591
TI  - Analysis of outcome in women with borderline glandular change on cervical
      cytology.
AB  - OBJECTIVE: To review the outcome of women presenting with borderline glandular
      smear on cervical cytology and to investigate correlation between cytology,
      colposcopy and histology and subsequent smear history. STUDY DESIGN: A 5 year
      retrospective analysis of outcome in all women reported with borderline glandular
      changes on cytology between 2001 and 2005 at the John Radcliffe Hospital, Oxford,
      and Cheltenham General Hospital, Gloucestershire, was performed. Cytology,
      colposcopy, histology and follow-up cytology data at 6, 12 and 24 months after
      index smear were collated. RESULTS: Of 92 women with borderline glandular smears,
      56 were referred for colposcopy. This accounts for 0.9% of the total referral
      (6293) to the colposcopy units. A significant rate of abnormal histology was
      noted, with CIN 1, 2, 3, CGIN or worse in 20 women (36%) and benign pathology in
      18 women (32%). Colposcopy had a sensitivity of 82%, specificity of 39%, negative
      predictive value of 80% and positive predictive value of 49% in predicting
      abnormal (premalignant/malignant) histology. Only one woman with normal histology
      at presentation had subsequent abnormal cytology (1/31), whereas abnormal
      histology at presentation was strongly associated with subsequent abnormality on
      follow-up cytology over 24 months (8/21) with a p value=0.0058. CONCLUSION:
      Colposcopic examination and biopsy of colposcopically identified abnormalities is
      reliable, with negative colposcopy having a high negative predictive value. We
      also recommend thorough colposcopic examination before any invasive investigation
      as over treatment may impact on the future reproductive outcome [1].

PMID- 19740592
TI  - Histological response is not a prognostic factor after neoadjuvant chemotherapy
      in advanced-stage ovarian cancer with no residual disease.
AB  - OBJECTIVE: The aim of this study was to evaluate the prognostic impact of the
      histological response at the time of interval debulking surgery (IDS) in patients
      treated with neoadjuvant chemotherapy (NACT) for unresectable advanced-stage
      ovarian cancer (ASOC). STUDY DESIGN: A retrospective study to select cases
      fulfilling 4 inclusion criteria: (1) patients with unresectable ASOC; (2) at
      least 3 courses of platinum and paclitaxel NACT; (3) patients who underwent IDS
      after NACT and who were free of macroscopic residual disease at the end of
      debulking surgery and (4) histologic analysis of specimens performed in the same
      institution. Patients were classified into 3 groups according to the histological
      response to NACT group 1: no histologic residual disease; group 2: persistent
      residual disease but with marked histological changes and group 3: persistence of
      at least 1 site with no changes in the tumour. Survival was compared. RESULTS:
      Fifty-eight patients (49 stage IIIC and 9 stage IV) fulfilled inclusion criteria.
      Respectively 8, 14 and 36 patients were in groups 1, 2 and 3. The median duration
      of follow-up was 41 months. Three-year event-free survival in groups 1, 2 and 3
      was respectively: 63%, 12% and 19% (p=.02). CONCLUSIONS: These results suggest
      that the degree of the histological response has a limited impact on survival
      when complete debulking surgery is achieved at IDS. The degree of tumour cell
      viability after initial chemotherapy is not a reliable marker for modifying
      chemotherapy after debulking surgery in such patients.

PMID- 19740593
TI  - Mapping of the fate of cell lineages generated from cells that express the Wnt4
      gene by time-lapse during kidney development.
AB  - The Wnt4 gene encodes a secreted signaling molecule controlling the development
      of several organs, such as the kidney, adrenal gland, ovary, mammary gland and
      pituitary gland. It is thought to act in the embryonic kidney as an auto-inducer
      of nephrogenesis controlling mesenchyme-to-epithelium transition, and Wnt4
      deficient mice die soon after birth, probably of kidney failure. Given the
      requirement for Wnt4 signaling in the control of organogenesis, the targeting of
      Cre recombinase under the control of the Wnt4 promoter would provide a valuable
      tool for fate mapping and functional genomics. We report here on the generation
      and characterization of a Wnt4(EGFPCre) knock-in allele where the EGFPCre fusion
      cDNA and Neo selection cassette were targeted into the Wnt4 locus. EGFP-derived
      fluorescence was observed in the pretubular aggregates of the E14.5 embryonic
      kidney that normally express Wnt4 mRNA. Characterization of the pattern of
      recombination of the floxed Rosa26(LacZ) reporter with the Wnt4(EGFPCre) allele
      revealed that in addition to the embryonic kidney, reporter-derived staining was
      observed in the embryonic gonad, spinal cord, lung and adrenal gland, i.e. the
      sites of Wnt4 gene expression. Time-lapse fate mapping of the Wnt4(EGFPCre)
      activated yellow fluorescent protein (YFP) from the Rosa26 locus in organ culture
      revealed that the cells that had expressed the Wnt4 gene contributed to the
      nephrons, some of the cells around the stalk of the developing ureter and also
      certain presumptive medullary stromal cells. Moreover, the time-lapse movies
      suggested that the first few pretubular cell aggregates may not mature into
      nephrons but instead appear to disintegrate. In association with this,
      Rosa26(YFP)-positive stromal cells emerge around these disintegrating structures.
      Such cells may be transient, since their derivatives are neither detected later
      in the more mature kidney nor is there an overlap of the Wnt4(EGFPCre);
      Rosa26(LacZ)-marked cells with those of the endothelial cells, the smooth muscle
      cells or the macrophages. The Wnt4(EGFPCre) allele provides a useful new tool for
      conditional mutagenesis and provides the first time-lapse-based map of the fate
      of nephron precursor cells.

PMID- 19740594
TI  - Toward standardized anatomical classifications of small renal tumors.

PMID- 19740595
TI  - An updated critical analysis of the treatment strategy for newly diagnosed high
      grade T1 (previously T1G3) bladder cancer.
AB  - CONTEXT: High-grade T1 (formerly T1G3) bladder cancer (BCa) has a high propensity
      to recur and progress. As a result, decisions pertaining to its treatment are
      difficult. Treatment with bacillus Calmette-Guerin (BCG) risks progression and
      metastases but may preserve the bladder. Cystectomy may offer the best
      opportunity for cure but is associated with morbidity and a risk of mortality,
      and it may constitute potential overtreatment for many cases of T1G3 tumours. For
      purposes of this review, we continue to refer to high-grade T1 lesions as "T1G3."
      OBJECTIVE: To review the current literature on the management of T1G3 BCa and to
      provide recommendations for its treatment. EVIDENCE ACQUISITION: A National
      Center for Biotechnology Information (NCBI) PubMed search for relevant articles
      published between 1996 and 9 January 2009 was performed using the Medical Subject
      Headings "T1G3" or "T1" and "Bladder cancer." Articles relevant to the treatment
      of T1G3 BCa were retained. EVIDENCE SYNTHESIS: The diagnosis of T1G3 disease is
      difficult because pathologic staging is often unreliable and because of the risk
      of significant understaging at initial transurethral resection (TUR) of bladder
      tumour. A secondary restaging TUR is recommended for all cases of T1G3. A single
      dose of immediate post-TUR chemotherapy is recommended. For a bladder-sparing
      approach, intravesical BCG should be given as induction with maintenance dosing.
      Immediate or early radical cystectomy (RC) should be offered to all patients with
      recurrent or multifocal T1G3 disease, those who are at high risk of progression,
      and those failing BCG treatment. CONCLUSIONS: Both bladder preservation and RC
      are appropriate options for T1G3 BCa. Risk stratification of patients based on
      pathologic features at initial TUR or at recurrence can select those most
      appropriate for bladder preservation compared to those for whom cystectomy should
      be strongly considered.

PMID- 19740596
TI  - Primary intracranial leiomyomas: Report of two cases and review of the
      literature.
AB  - A leiomyoma is a benign neoplasm composed of smooth muscle cells that commonly
      occurs in the genitourinary and gastrointestinal tracts. Primary intracranial
      leiomyoma, however, is extremely rare and only a few cases have been reported to
      date. In this study, we present two cases of primary intracranial leiomyomas in
      middle-aged men. Magnetic resonance images (MRI) showed lesions with homogeneous
      low signals on T1-, T2-, diffusion-weighted, and FLAIR sequences. Tumors were
      totally removed and there was no evidence of recurrence in the follow-up study.
      Pathological analysis with immunohistochemistry revealed that tumors had
      characteristics of benign smooth muscles. A review of relevant literature has
      been conducted.

PMID- 19740597
TI  - Genomic gain of 5p15 leads to over-expression of Misu (NSUN2) in breast cancer.
AB  - We have examined expression of the Myc target gene Misu (NSUN2) in breast cancer.
      There was extensive copy number gain, and increased mRNA and protein levels, of
      Misu in approximately one third of breast cancer cell lines and primary tumours
      examined, irrespective of tumour subtype. Genes on 5p15.31-33, where Misu is
      located, showed evolutionary synteny. siRNA-mediated knockdown of Misu reduced
      cell number in over half of the cell lines tested, irrespective of estrogen
      receptor status. We conclude that Misu is up-regulated in a substantial
      proportion of breast cancers and has therapeutic potential as a drug target.

PMID- 19740598
TI  - Modification of chloromethylated polystyrene with 2-mercabtobenzothiazole for
      application as a new sorbent for preconcentration and determination of Ag+ from
      different matrices.
AB  - Chloromethylated polystyrene polymer (CMSP) modified with 2-mercabtobenzothiazole
      (MBT) has been developed for the selective separation and/or preconcentration of
      silver. The modified polymer (CMS-MBT) was characterized by elemental analysis
      and IR spectra. Batch and column modes were applied. The newly designed polymer
      quantitatively sorbed Ag(+) at pH 2 when the flow rate is 5 ml min(-1). The
      maximum sorption capacity was 0.493 mmol g(-1) while the preconcentration factor
      was 250 for Ag(+). The detection limit was 8 ng ml(-1). The desorption was
      effective with 5 ml of 2 mol l(-1) HNO(3) prior to detection using AAS. The
      modified polymer was highly ion-selective in nature even in the presence of large
      concentrations of electrolytes or organic media, with a preconcentrating ability
      for Ag(+). The utility of the modified polymer to synthetic and drugs samples
      showed RSD values of <3% reflecting its accuracy and reproducibility.

PMID- 19740599
TI  - Synthesis of nucleated glass-ceramics using oil shale fly ash.
AB  - Nucleated glass-ceramics materials were produced from oil shale fly ash obtained
      from Huadian thermal power plant in China with the addition of analytic reagent
      CaO. On basis of differential thermal analysis (DTA) results, the nucleation and
      crystallization temperature of two parent glass samples with different alkalinity
      (Ak=m(CaO)/m(SiO(2)) were identified as Tn(1)=810 degrees C, Tc(1)=956 degrees C
      and Tn(2)=824 degrees C, Tc(2)=966 degrees C, respectively. X-ray diffraction
      (XRD) analysis of the produced nucleated glass-ceramics materials revealed that
      there was a coexistence phenomenon of multi-crystalline phase and the main
      crystalline phase was anorthite ([Ca,Na][AI,Si](2)Si(2)O(8)). The microstructure
      of the glass-ceramics materials was examined by scanning electron microscope
      (SEM). SEM observation indicated that there was an increase in the quantity of
      sphere-shaped crystals when crystallization time increased. Furthermore, the
      increase of alkalinity caused more amorphous phase occurring in glass-ceramics
      materials. Through the tests of physical and mechanical properties, the glass
      ceramics materials with more crystalline phase and fine microstructure had high
      density, fine performance of resisting compression (328.92 MPa) and negligible
      water absorption. Through chemical resistance tests, the glass-ceramics samples
      showed strong corrosion resistance. Overall results indicated that it was a
      feasible attempt to produce nucleated glass-ceramics materials for building and
      decorative materials from oil shale fly ash.

PMID- 19740600
TI  - Heat treatment effects on the characteristics and sonocatalytic performance of
      TiO2 in the degradation of organic dyes in aqueous solution.
AB  - The ambient sonocatalytic degradation of congo red, methyl orange, and methylene
      blue by titanium dioxide (TiO(2)) catalyst at initial concentrations between 10
      and 50mg/L, catalyst loadings between 1.0 and 3.0mg/L and hydrogen peroxide
      (H(2)O(2)) concentrations up to 600 mg/L is reported. A 20 kHz ultrasonic
      processor at 50 W was used to accelerate the reaction. The catalysts were exposed
      to heat treatments between 400 and 1000 degrees C for up to 4h to induce phase
      change. Sonocatalysts with small amount of rutile phase showed better
      sonocatalytic activity but excessive rutile phase should be avoided. TiO(2)
      heated to 800 degrees C for 2h showed the highest sonocatalytic activity and the
      degradation of dyes was influenced by their chemical structures, chemical phases
      and characteristics of the catalysts. Congo red exhibited the highest degradation
      rate, attributed to multiple labile azo bonds to cause highest reactivity with
      the free radicals generated. An initial concentration of 10mg/L, 1.5 g/L of
      catalyst loading and 450 ppm of H(2)O(2) gave the best congo red removal
      efficiency of above 80% in 180 min. Rate coefficients for the sonocatalytic
      process was successfully established and the reused catalyst showed an activity
      drop by merely 10%.

PMID- 19740601
TI  - Preparation of nano-Cu2O/TiO2 photocatalyst from waste printed circuit boards by
      electrokinetic process.
AB  - It is difficult for separation and reutilization of Cu in waste printed circuit
      boards (PCBs) due to the heterogeneous mix of polymer materials, multiple kinds
      of metals and glass fiber. In this study, waste PCBs were pretreated by
      supercritical water oxidation (SCWO), then introduced into an electrokinetic (EK)
      system with nano-TiO(2) suspension as catholyte. In the EK process, Cu could be
      leached and reduced separately from the complicated multi-metal system in cathode
      compartment, and Cu(2)O could be formed in nano-size on TiO(2) surface. The
      properties of the composite catalysts Cu(2)O/TiO(2) were examined and their
      photocatalytic efficiencies were determined for methylene blue (MB) degradation.
      The results indicated that the catalytic effect increased with increasing EK
      preparation time but decreased afterwards. The most effective catalyst (4.53 wt.%
      Cu(2)O/TiO(2)), whose degradation ability was found to be much higher in
      comparison with commercial P25, was prepared by 6h EK treatment. It was found
      that the loading of Cu(2)O on TiO(2) surface could greatly enhance the
      photocatalytic effect of the catalyst. It is believed that the EK technology is
      effective and green for direct preparation of high value-added Cu nanocomposite
      materials from waste PCBs or other Cu-rich wastes.

PMID- 19740602
TI  - Spectroscopic investigation of sulfonate phthalocyanine to probe enzyme reactions
      for heavy metals detection.
AB  - Optical absorption and Raman spectra of the sulfonated copper phthalocyanine
      (CuTsPc) layer were exploited for detection of cadmium (Cd) contaminants in
      water. Acetylcholine esterase was immobilized by freely suspending them in
      calcium alginate microbeads and this gel was then spincoated on the drop cast
      sulfonated copper phthalocyanine film on a glass substrate to form a bilayer. The
      inhibition of catalytic reaction between acetylcholine chloride and enzyme due to
      Cd contaminants was monitored by recording changes in spectra of drop cast CuTsPc
      as an indicator. The detection limit of cadmium content in water was found to be
      1 ppm.

PMID- 19740603
TI  - Chitosan beads as barriers to the transport of azo dye in soil column.
AB  - The development of chitosan-based materials as useful adsorbent polymeric
      matrices is an expanding field in the area of adsorption science. Although
      chitosan has been successfully used for the removal of dyes from aqueous
      solutions, no consideration is given to the removal of dyes from contaminated
      soils. Therefore this study focuses on the potential use of chitosan as an in
      situ remediation technology. The chitosan beads were used as barriers to the
      transport of a reactive dye (Reactive Black 5, RB5) in soil column experiments.
      Batch sorption experiments, kinetic and equilibrium, were performed to estimate
      the sorption behavior of both chitosan and soil. The chitosan beads were prepared
      in accordance with published literature and a synthetic soil was prepared by
      mixing quantities of sand, silt and clay. The synthetic soil was classified
      according to British Standards. Calcium chloride was used as tracer to define
      transport rates and other physical experimental parameters. Dye transport
      reaction parameters were determined by fitting dye breakthrough curves (BTCs) to
      the HYDRUS-1D version 4.xx software. Fourier Transform-Infra Red (FT-IR)
      spectroscopy was used to reveal the sorption mechanism. The study showed that
      chitosan exhibited a high sorption capacity (S(max)=238 mg/g) and pseudo-first
      sorption rate (k(1)=1.02 h(-1)) coupled with low swelling and increased
      retardation for the azo dye tested. Thus it has potential as a Permeable Reactive
      Barrier (PRB) for containment and remediation of contaminated sites.

PMID- 19740604
TI  - Toxicity and organic content characterization of olive oil mill wastewater
      undergoing a sequential treatment with fungi and photo-Fenton oxidation.
AB  - Olive oil mill wastewater (OOMW) is responsible for serious environmental
      problems. In this study, the efficiency of two treatments involving fungi and
      photo-Fenton oxidation, sequentially applied to OOMW was analyzed for organic
      compounds degradation and toxicity mitigation. The treatment with fungi
      (especially Pleurotus sajor caju) of diluted OOMW samples promoted a reduction of
      their acute toxicity to Daphnia longispina. Although this fungi species have not
      induced significant color reduction it was responsible for 72,91 and 77%
      reductions in chemical oxygen demand (COD), total phenolic and organic compound
      contents. After biological treatment, photo-Fenton oxidation seemed to be an
      interesting solution, especially for color reduction. However, the OOMWs remained
      highly toxic after photo-Fenton oxidation. Considering the second sequence of
      treatments, namely photo-Fenton oxidation followed by biological treatment, the
      former revealed, once more, a great potential because it can be applied to non
      diluted OOMW, with significant reductions in COD (53-76%), total phenolic content
      (81-92%) and organic compounds content (100%). Despite fungal species still have
      demonstrated a high capacity for bioaccumulation of organic compounds, resulting
      from photo-Fenton oxidation, the biological treatment did not cause substantial
      benefits in terms of COD, total phenolic content and toxicity reduction.

PMID- 19740605
TI  - Reduction of COD and color of dyeing effluent from a cotton textile mill by
      adsorption onto bamboo-based activated carbon.
AB  - In this work, activated carbon was prepared from bamboo waste by chemical
      activation method using phosphoric acid as activating agent. The activated carbon
      was evaluated for chemical oxygen demand (COD) and color reduction of a real
      textile mill effluent. A maximum reduction in color and COD of 91.84% and 75.21%,
      respectively was achieved. As a result, the standard B discharge limit of color
      and COD under the Malaysian Environmental Quality act 1974 was met. The
      Freundlich isotherm model was found best to describe the obtained equilibrium
      adsorption data at 30 degrees C. The Brunauer-Emmett-Teller (BET) surface area,
      total pore volume and the average pore diameter were 988.23 m(2)/g, 0.69 cm(3)/g
      and 2.82 nm, respectively. Various functional groups on the prepared bamboo
      activated carbon (BAC) were determined from the FTIR results.

PMID- 19740606
TI  - Accumulation and acute toxicity of silver in Potamogeton crispus L.
AB  - In the present study, Potamogeton crispus L. plants exposed to various
      concentrations of silver (Ag) (5, 10, 15, and 20 microM) for 5d were investigated
      to determine the accumulating potential of Ag and its influence on nutrient
      elements, chlorophyll pigments and fluorescence, various antioxidant enzymes and
      compounds, adenosine triphosphate (ATP), protein content and ultrastructure. The
      accumulation of Ag was found to increase in a concentration dependent manner with
      a maximum of 29.3 microg g(-1) at 20 microM. The nutrient elements (except Ca),
      photosynthetic pigments, chlorophyll a fluorescence parameters (Fo, Fv, Fv/Fm,
      Fv/Fo), malondialdehyde (MDA), ATP, peroxidase (POD) activity, ascorbate (AsA),
      reduced glutathione (GSH) and protein contents decreased significantly as
      concentration of Ag augmented. In contrast, an induction in SOD activity was
      recorded, while an initial rise in Ca content and CAT activity was followed by
      subsequent decline. Morphological symptoms of senescence phenomena such as
      chlorosis and damage of chloroplasts and mitochondria were observed even at the
      lowest concentration of Ag, which suggested that Ag hastened the senescence of
      the tested plants. The loss of nutrients and chlorophyll content and damage of
      chloroplasts were associated with disturbances in photosynthetic capacity as
      indicated by the quenching of chlorophyll a fluorescence. Decreased chlorophyll
      and protein contents suggest oxidative stress induced by Ag. In addition, both
      the reduction of ATP and the damage to the ultrastructure of organelles were
      indicative of general disarray in the cellular functions exerted by Ag.

PMID- 19740607
TI  - Thermal stability and kinetic of decomposition of nitrated HTPB.
AB  - Nitrated HTPB (NHTPB) is a potential energetic binder to replace the conventional
      inert binder, HTPB, for the composite solid propellants and plastic bonded
      explosives (PBXs). The thermal stability of the NHTPB sample with 10% double
      bonds converted to dinitrate ester group (10% NHTPB) was evaluated by high
      pressure differential scanning calorimeter (PDSC) measurement. The influences of
      pressure (0.1, 2.5 and 5.0 MPa) and the heating rate (4, 6, 8 and 10 degrees C
      min(-1)) on the DSC behavior of the 10% NHTPB sample were investigated. The
      decomposition temperature of this compound decreased with the increase of
      pressure, meanwhile, increased as the heating rate increasing. The thermal
      decomposition at 150-250 degrees C followed a first-order law. The kinetic
      parameters and thermodynamic parameters for the 10% NHTPB sample at 150-250
      degrees C under ambient pressure were obtained from the DSC data by non
      isothermal methods proposed by ASTM E698 and Flynn-Wall-Ozawa. The critical
      temperature for this compound was estimated at about 154 degrees C.

PMID- 19740608
TI  - Stimulation of reactive dye removal by cyanobacteria in media containing
      triacontanol hormone.
AB  - In this study, Reactive Red, Remazol Blue, and Reactive Black B removal
      capacities of Synechocystis sp. and Phormidium sp. were investigated. The
      microorganisms were cultivated in 100ml BG 11 medium and incubated at 30 degrees
      C under continuous illumination (12.5 wm(-2) (2400 lx)) for 20 days in plant
      growth chamber. Trials were carried out at pH 9.5 for Reactive Red, pH 8.5 for
      Remazol Blue and Reactive Black B removal in media without and with triacontanol
      (TRIA). Removal capacities of Synechocystis sp. and Phormidium sp. were found
      higher in media containing TRIA. So that, Synechocystis sp. and Phormidium sp.
      removed Reactive Red with 25.7% and 35.4%, Remazol Blue with 37.5% and 25.5%, and
      Reactive Black B with 29.2% and 28.3% yield at 25 mg l(-1) dye concentrations,
      respectively. There is no report investigating dye removal by Synechocystis sp.
      and removal of pollutants in media including TRIA hormone. Our data indicated the
      cyanobacteria tested in this study were suitable for effective treatment
      processes of such wastewaters including reactive dyes, and their removal capacity
      could be increased by TRIA, through stimulation of the biomass production.

PMID- 19740609
TI  - Chromium (VI) reduction in aqueous solutions by Fe3O4-stabilized Fe0
      nanoparticles.
AB  - This paper describes the use of highly reactive magnetite (Fe(3)O(4))
      nanoparticles-stabilized Fe(0) nanocomposites for the reduction and mitigation of
      hexavalent chromium Cr(VI) species in aqueous solutions. Higher proportions of
      Fe(3)O(4) in the nanocomposites could increase the rate of Cr(VI) reduction. In
      the absence of magnetite, the Cr(VI) mitigation rate was just 51.4% after 60 min
      of reaction, while with an initial Fe(3)O(4) mass loading of 3 g l(-1), the
      Cr(VI) mitigation rate was nearly 100% after 60 min. The optimal ratio of
      Fe(3)O(4):Fe(0) for the mitigation of Cr(VI) was found to be 40:1. Otherwise,
      solution pHs significantly affected the rate of Cr(VI) reduction, with reactions
      occurring more rapidly under acidic or neutral than basic conditions. It is
      hypothesized that the high efficiency of the Fe(3)O(4) nanoparticles-stabilized
      Fe(0) nanocomposites for Cr(VI) reduction was a direct result of the attachment
      of Fe(0) nanoparticles to the surface of magnetite, which prevents the
      aggregation of nano-Fe(0), moreover, the electron transfer during the reduction
      process most likely takes place via Fe(0) nanoparticles that are located at the
      magnetite octahedral sites, which are versatile redox centers as they can
      accommodate both Fe(III) and Fe(II), and this will promote the reduction of
      Cr(VI). Cr(VI) reduction is coupled with nano-Fe(0) oxidation. Nano-Fe(0)
      particles are located at the magnetite octahedral sites. Ions of Fe(II) and
      Fe(III) accommodated by magnetite octahedral sites are products of nano-Fe(0)
      oxidation. Therefore, Cr(VI) reduction is mediated either by nano-Fe(0) (direct
      reduction) or Fe(II) species (indirect reduction). Additionally, catalytic Cr(VI)
      reduction by molecular H(2) (or atomic H) is possible.

PMID- 19740610
TI  - Induction of protective immunity by multiantigenic DNA vaccine delivered in
      attenuated Salmonella typhimurium against Toxoplasma gondii infection in mice.
AB  - Toxoplasma gondii, capable of infecting all warm blooded animals, is one of the
      most successful parasites worldwide. It was reported that the single-gene vaccine
      with SAG1 or MIC3 could only produce partial protection against T. gondii and
      multiantigenic vaccines were more effective than single ones. In the present
      study, a multiantigenic DNA vaccine delivered by attenuated Salmonella
      typhimurium (ZJ111/pSAG1-MIC3) was constructed, which expresses surface protein
      SAG1 and micronemal protein MIC3. The safety and stability of ZJ111/pSAG1-MIC3
      were evaluated and immune response with ZJ111/pSAG1 and ZJ111/pMIC3 were
      compared. The results of lymphocyte proliferation assay, antibody and cytokine
      determination show that mice immunized with ZJ111/pSAG1-MIC3 elicited stronger
      humoral and Th1-type cellular immune responses than other groups. The mice
      immunized with ZJ111/pSAG1-MIC3 also exhibited significant higher survival time
      after challenged with T. gondii RH strain. The current study shows that the oral
      multiantigenic DNA vaccine, ZJ111/pSAG1-MIC3, produces partial protection against
      T. gondii challenge.

PMID- 19740612
TI  - Randomized response estimates for doping and illicit drug use in elite athletes.
AB  - BACKGROUND: To date, there are estimates for the percentage of unknown cases of
      doping and illicit drug use in fitness sports, but not for elite sports. This can
      be attributed to the problem of implementing questionnaires and surveys to get
      reliable epidemiological estimates of deviant or illicit behaviour. METHODS: All
      athletes questioned were subject to doping controls as members or junior members
      of the national teams. In order to estimate the prevalence of doping and illicit
      drug abuse, the athletes were either issued an anonymous standardized
      questionnaire (SQ; n=1394) or were interviewed using randomized response
      technique (RRT; n=480). We used a two-sided z-test to compare the SQ and RRT
      results with the respective official German NADA data on the prevalence of
      doping. RESULTS: Official doping tests only reveal 0.81% (n=25,437; 95% CI: 0.70
      0.92%) of positive test results, while according to RRT 6.8% (n=480; 95% CI: 2.7
      10.9%) of our athletes confessed to having practiced doping (z=2.91, p=0.004). SQ
      and RRT both revealed a prevalence of about 7% for illicit drug use, but SQ
      failed to indicate a realistic prevalence of doping (0.20%; 95% CI: 0.02-0.74%).
      CONCLUSIONS: We demonstrate for the first time that data from official doping
      tests underestimate the true prevalence of doping in elite sports by more than a
      factor of eight. Our results indicate that implementing RRT before and after anti
      doping measures could be a promising method for evaluating the effectiveness of
      anti-doping programs.

PMID- 19740613
TI  - Methicillin-resistant Staphylococcus aureus in horses and horse personnel: an
      investigation of several outbreaks.
AB  - At the Veterinary Microbiological Diagnostic Center, the Netherlands, the
      percentage of methicillin-resistant Staphylococcus aureus (MRSA) isolates found
      in equine clinical samples increased from 0% in 2002 to 37% in 2008. MRSA of spa
      type t064, belonging to MLST ST8 and spa-types t011 and t2123, both belonging to
      the livestock-associated MLST ST398, predominated. During an outbreak of post
      surgical MRSA infections in horses at a veterinary teaching hospital in
      2006/2007, MRSA isolates of spa-type t2123 were cultured from 7 horses and 4/61
      personnel which indicated zoonotic transmission. After intervention the outbreak
      stopped. However, another outbreak occurred in 2008, where 17 equine MRSA
      isolates of spa-type t011 (n=12), t2123 (n=4), and t064 (n=1) were found. This
      time, 16/170 personnel were positive for MRSA with spa-type t011 (n=11) and t2123
      (n=5). Personnel in close contact with horses were more often MRSA-positive
      (15/106) than those without (1/64). Screening of horses upon admission showed
      that 9.3% were MRSA-positive predominantly with spa-type t011. Weekly cross
      sectional sampling of all hospitalized horses for 5 weeks showed that 42% of the
      horses were MRSA-positive at least once, again predominantly with spa-type t011,
      which suggests that nosocomial transmission took place. Fifty-three percent of
      the environmental samples were MRSA-positive, including samples from students'
      and staff members' rooms, and all were spa-type t011. This indicates that humans
      contribute to spreading the organism. Culturing of samples employing high-salt
      pre-enrichment performed better than a comparable method without pre-enrichment.
      Our results show that nosocomial transmission occurs in equine clinics and
      suggests that personnel play a role in the transmission.

PMID- 19740614
TI  - Infant outcomes of assisted reproduction.
AB  - Assisted reproductive technologies (ART) have become widely used in the treatment
      of subfertility over the last 30 years. Currently 1.7% of all births in the UK
      occur after assisted conception. This review summarises work that has been
      undertaken to investigate health outcomes of these children and summarises areas
      where uncertainty continues to exist. Much of the adverse health outcomes of
      children born after ART are related to higher order birth; however evidence
      suggests adverse perinatal outcomes in singletons as well as twins and triplets.
      The cause of adverse health outcomes in ART conceived children is as yet unclear
      and studies investigating causal factors such as underlying subfertility are
      discussed.

PMID- 19740611
TI  - Geographic clustering of underage drinking and the influence of community
      characteristics.
AB  - The aim of this paper was to examine the extent to which underage drinking
      clusters geographically in a sample of communities, and to investigate the manner
      in which community-level contexts are related to this process. We used data from
      a randomized community trial of underage drinking to provide the first
      quantitative estimates of the magnitude of the geographic clustering of underage
      drinking based upon pairwise odds ratios (PWORs). The Enforcing Underage Drinking
      Laws Randomized Community Trial provided data from repeated cross-sectional
      samples of youth aged 14-20 from 68 communities surveyed in 2004, 2006, and 2007
      (n=18,730). Past 30-day drinking, binge drinking, getting drunk, experiencing non
      violent consequences as a result of drinking and making a purchase attempt all
      significantly clustered within-communities with PWORs ranging from 1.05 to 1.21.
      After adjustment for individual-level characteristics, results remained
      relatively unchanged. However, there was evidence that the magnitude of the
      clustering varied as a function of neighborhood disadvantage, neighborhood
      disorder, and family structure. Clustering of drunkenness and experiencing non
      violent consequences as a result of drinking was greatest in the least
      economically disadvantaged and least disordered communities with the greatest
      percentage of married-couple families. The clustering of making a purchase
      attempt, however, was greatest in more disordered communities, specifically the
      largest communities with the highest degree of residential mobility and housing
      density. These findings that clustering of underage drinking behaviors varies by
      community context has the potential for identifying the types of communities to
      target for underage drinking behavior-specific preventive interventions.

PMID- 19740615
TI  - A fast ultrasound-assisted extraction procedure for trace elements determination
      in hair samples by ICP-MS for forensic analysis.
AB  - An ultrasound-assisted extraction method is proposed for the determination of
      trace elements in hair samples by inductively coupled plasma-mass spectrometry
      (ICP-MS) for forensic investigation. Prior to analysis, 25mg of hair samples were
      accurately weighed into (15 mL) conical tubes. Then, 2 mL of 20% HNO(3) is added
      to the samples, sonicated at 2 min (50W, 100% amplitude), and then further
      diluted to 10 mL with Milli-Q water. Resulted diluted slurries are centrifuged
      and the analytes are directly determined in the supernatant. Calibrations against
      aqueous solutions were carried out with rhodium as internal standard. The method
      was successfully applied for the extraction of Al, As, Ba, Be, Cd, Co, Cr, Cu,
      Mn, Pb, Tl, U, V and Zn with a method detection limit (3s, n=20) of 0.1, 0.4,
      0.2, 0.09, 0.08, 0.04, 0.1, 2.9, 1.0, 0.9, 0.04, 0.05, 0.1 and 4.2 ng/g,
      respectively. Method accuracy is traceable to Certified Reference Materials
      (CRMs) 85 and 86 human hair from the International Atomic Energy Agency (IAEA).
      Additional validation data are provided based on the analysis of hair samples
      from the trace elements intercomparison program operated by the Institut National
      de Sante' Publique du Quebec, Canada. The proposed method is very simple and can
      be applied for forensic purposes with the elimination of sample digestion step
      prior to analysis. Then, a considerable improvement in the sample throughput is
      archived with the use of the proposed method.

PMID- 19740616
TI  - Voxel-based analysis of white matter during adolescence and young adulthood.
AB  - PURPOSE: To evaluate differences in age-related brain white matter by voxel-based
      analysis of healthy adolescents and young adults. MATERIALS AND METHODS: Echo
      planar diffusion-tensor magnetic resonance (MR) imaging was performed in healthy
      subjects of 3 groups (aged 11-13, 16-18 and 23-25, respectively). Linear
      correlative analyses were applied to determining age-related fractional
      anisotropy (FA) and mean diffusivity (MD), and t-test was performed to compare FA
      and mean diffusion maps between different age groups. RESULTS: Significant
      positive correlation of FA with age was found in the internal capsule, the
      external capsule, the frontal white matter, and the body and genu of the corpus
      callosum. Compared with the 11-13 age group, FA in the 16-18 age group increased
      in the internal capsule, the frontal white matter, the body and the splenium of
      the corpus callosum. Compared to the 16-18 age group, FA in the 23-25 age group
      increased in the frontal white matter, the posterior limb of internal capsule,
      and the genu of the corpus callosum. Statistically significant negative
      correlation of the mean diffusion with age was found in the frontal and parietal
      white matter. Compared with the 11-13 age group, MD in the 16-18 age group
      decreased in the prefrontal and the temporo-parietal white matter. Compared with
      the 16-18 age group, MD in the 23-25 age group decreased in the frontal white
      matter. CONCLUSION: Diffusion-tensor MR imaging results indicate that white
      matter maturation assessed at different ages involves increases in FA and
      decreases in mean diffusion of the white matter during adolescence and young
      adulthood. FA and mean diffusion may reflect different physiologic processes in
      healthy adolescents and young adults. Taken together, these data show that
      maturation of white matter is an important part of brain maturation during
      adolescence and young adulthood.

PMID- 19740617
TI  - Combined magnetic resonance imaging and spectroscopy in the assessment of high
      grade prostate carcinoma in patients with elevated PSA: a single-institution
      experience of 356 patients.
AB  - PURPOSE: To assess the ability of combined whole-prostate magnetic resonance
      imaging and magnetic resonance spectroscopy imaging (MRI+MRSI) to predict the
      presence or absence of high grade (Gleason 4+3 or higher) prostate carcinoma in
      men with elevated PSA. MATERIALS AND METHODS: Between March 2002 and September
      2007, 356 subjects (mean serum PSA 11.5 ng/ml, range 0.4-133.0 ng/ml) were
      examined with fast-T2-weighted magnetic resonance imaging (MRI) and 3D-magnetic
      resonance spectroscopy imaging (MRSI) on a 1.5T scanner. Prostate cancer was
      histopathologically proven in 220 patients (41 with high grade and 179 with lower
      grade cancer) and non-evidence of cancer was determined after at least 12 months
      (mean 21 months) clinical follow-up in 136 subjects. The sensitivity, false
      positive rate, and negative predictive value of MRI+MRSI were calculated using
      histopathology and follow-up results as reference standard. RESULTS: MRI+MRSI had
      a significantly higher sensitivity for high grade tumors (92.7%) than for lower
      grade tumors (67.6%), and was false positive in only 7.4% of patients with non
      evidence of prostate cancer. For exclusion of a high grade tumor, MRI+MRSI had a
      negative predictive value of 98.4%. CONCLUSIONS: MRI+MRSI holds great potential
      for predicting presence or absence of high grade tumors in men with elevated PSA.
      This can be important in the selection of patients for active surveillance, or in
      the decision to rebiopsy patients with prior negative biopsies.

PMID- 19740618
TI  - Analysis of hesperetin enantiomers in human urine after ingestion of blood orange
      juice by using nano-liquid chromatography.
AB  - Hesperetin (HT) is a flavanone abundantly found in citrus fruits. It has been
      reported that HT possesses significant antioxidant, anticancer, anti-inflammatory
      and analgesic activities. This explains the necessity of developing new methods
      more powerful and sensitive for analyzing HT in biological fluids. Taking into
      account the chiral nature of HT, the study of the stereospecific kinetics of in
      vitro and in vivo metabolism and tissue distribution could be a useful tool for
      further understanding stereoselective biotransformations in human body. A simple
      nano-liquid chromatographic method for the determination of the enantiomeric
      composition of hesperetin in human urine was developed. Chiral separation was
      achieved using a 100 microm I.D. capillary, packed with phenyl-carbamate-propyl
      beta-cyclodextrin stationary phase, employing a mobile phase composed by a
      mixture of triethylammonium acetate buffer (1%, v/v, pH 4.5) and water/methanol
      (30:70, v/v) at room temperature. The detection was done by using on-column UV
      detector at 205 nm. Calibration curves were linear in the studied concentration
      range from 0.25 to 25 microg/mL (r(2)>0.999). Precision assay was <4.5% and was
      within 3% at the limit of quantification (0.5 microg/mL). The recovery of 7
      ethoxycoumarin (IS), R- and S-hesperetin was greater than 82.48%, utilizing a
      liquid-liquid extraction procedure. The developed method was successfully applied
      to the determination of hesperetin enantiomers in urine samples obtained from a
      male volunteer, after the ingestion of 1L of a commercial blood orange juice.

PMID- 19740619
TI  - Surgical therapy of bilateral parathyroid carcinoma: report of an unusual case.

PMID- 19740620
TI  - [Exercise-induced thrombocytosis during rehabilitation after a fracture].

PMID- 19740621
TI  - [Tolerability profile of varenicline in current medical practice].
AB  - INTRODUCTION: Varenicline (Champix) was approved in France in 2006 as an aid to
      smoking cessation treatment. Although there is a consensus on its efficacy, its
      tolerability is debatable. This article sought to clarify its tolerability
      profile in current medical practice. MATERIALS AND METHODS: This retrospective
      study examined tolerance of varenicline prescribed to smokers who wanted to quit
      smoking in 10 "Stop-Smoking" consultation centers around France. It included all
      patients who used varenicline during the one-year (February 12, 2007, to February
      12, 2008) study period. RESULTS: At least one adverse event (AE) was reported by
      45.9% of the 338 patients, with a total of 343. AE incidence was higher among
      women (51.5%) than men (40.5%) (OR=1.56, 95% CI: 0.99-2.47, p=0.026). There were
      32 unexpected AEs, that is, not listed in the initial new drug application,
      reported by 23 patients, including 19 psychiatric AEs. Of the 8 serious AEs, 3
      were of neurological origin. CONCLUSION: This retrospective study confirmed the
      tolerability issues for varenicline, identified during the phase II-phase III
      development program and confirmed afterwards. It raises the following questions:
      Should varenicline be prescribed as a second-line therapy? Is there a patient
      type for which varenicline would be more - or less - appropriate? Can the
      tolerability profile be improved by reducing dosage while maintaining the level
      of efficacy or by co-administering symptomatic treatment more systematically?
      These are questions that new studies evaluating varenicline tolerability should
      answer.

PMID- 19740622
TI  - [Tunisian survey about organ donation, attitude and opinion?].
AB  - OBJECTIVE: In Tunisia organ donation stays very low. This is in part due to
      family's opposition in brain death situation. We realized a survey on a
      representative group of the Tunis's population (2.8 millions citizens) in the aim
      to clarify, among persons refusing organ donation, the prevalence of refusals
      determiners to individualize actions. METHODS: This survey was made in the region
      of Tunis between March 2006 and February 2007. The 16 questions of the survey
      were classified in four subjects: organ donation knowledge, opinion and attitude
      of the citizen, explicit justification and statements advanced in case of organ's
      donation refusal. RESULTS: 80.7% of citizens sounded are informed with the
      possibility of organ transplant in Tunisia. Only 50% of persons agree to accept
      organ donation after dying. Among the group refusing organ donation after dying,
      the absence of an understandable argument is recorded in 55.3% of cases. The
      violation on body integrity after death as well as religious obstruction are at
      the head of list of statements advanced in case of organ's donation refusal with
      respectively 79,9% and 63.1%. CONCLUSION: Relation researched between bodies and
      spirituality and individualism are the two explanations of this phenomenon of
      refusal of organ donation in Tunisia.

PMID- 19740623
TI  - A scale for distinguishing efficacy from effectiveness was adapted and applied to
      stroke rehabilitation studies.
AB  - OBJECTIVES: To apply a tool that purports to differentiate between efficacy and
      effectiveness studies to stroke rehabilitation trials and to evaluate its
      applicability and reliability. STUDY DESIGN AND SETTING: Three raters developed
      item operational definitions before independently applying the seven-item scale
      to 151 randomized controlled trials (RCT), published during or after 1997, that
      evaluated either a pharmacologic (P, n=78) or a nonpharmacologic (NP, n=73)
      intervention. Inter-rater reliability was assessed for both individual items and
      total scores, separately for P and NP trials. RESULTS: Item inter-rater
      reliability (multiple-rater kappa) ranged from 0.00 (95% CI [confidence
      interval]: -0.13, 0.13) to 0.85 (95% CI: 0.73, 0.98) and from 0.21 (95% CI: 0.08,
      0.34) to 0.79 (95% CI: 0.66, 0.92) for P and NP RCTs, respectively. For the total
      score (dichotomized), kappa values were 0.43 (95% CI: 0.31, 0.56) and 0.51 (95%
      CI: 0.37, 0.64) for P and NP trials, respectively. CONCLUSIONS: The tool provides
      a solid foundation on which to base further discussion of the differential
      criteria of efficacy-effectiveness trial design. Scale items should be properly
      operationalized depending on the research question of interest and evaluated for
      reliability before the scale is used for definitively judging a given study's
      design or the external validity of its results.

PMID- 19740624
TI  - Variation in results from randomized, controlled trials: stochastic or
      systematic?
AB  - OBJECTIVE: Randomized controlled trials (RCTs) are considered the highest grade
      of research evidence, yet properly conducted trials investigating the same
      association often yield conflicting results. Our objective was to assess whether
      variability in treatment protocols of RCTs investigating the same topic could
      explain distinct patterns of outcomes. STUDY DESIGN AND SETTING: A review of meta
      analyses identified clinical topics involving RCTs with variable pharmacologic
      dosing and disparate outcomes. Topics were retained if at least two pairs of
      trials had results suggesting contradictory yet strong exposure-outcome
      associations. RESULTS: The search yielded 6 clinical topics and 58 RCTs, and
      individual RCTs were classified into two groups, based on low and high dosages of
      the intervention. Aggregate odds ratios for studies in the low- and high-dose
      groups were often substantially discordant. For example, odds ratios were 1.76
      (95% confidence interval [CI]=1.02-3.03) for low-dose and 0.56 (95% CI=0.31-1.03)
      for high-dose trials evaluating low-molecular weight heparin and pulmonary
      embolism. In an exploratory analysis, outcomes for low- and high-dose groups in
      the comparison arms of trials (including patients assigned to placebo) had
      statistically significant differences in four of five analyzable topics,
      suggesting differences in patient characteristics across trials. CONCLUSION:
      Conflicting results from RCTs can represent a spectrum of "real" outcomes for
      specific treatments. Such trials are best evaluated by considering concurrently
      both the validity of study design as well as the generalizability of patients and
      interventions involved.

PMID- 19740625
TI  - Computational aspects in high intensity ultrasonic surgery planning.
AB  - Therapeutic ultrasound treatment planning is discussed and computational aspects
      regarding it are reviewed. Nonlinear ultrasound simulations were solved with a
      combined frequency domain Rayleigh and KZK model. Ultrasonic simulations were
      combined with thermal simulations and were used to compute heating of muscle
      tissue in vivo for four different focused ultrasound transducers. The simulations
      were compared with measurements and good agreement was found for large F-number
      transducers. However, at F# 1.9 the simulated rate of temperature rise was
      approximately a factor of 2 higher than the measured ones. The power levels used
      with the F# 1 transducer were too low to show any nonlinearity. The simulations
      were used to investigate the importance of nonlinarities generated in the
      coupling water, and also the importance of including skin in the simulations.
      Ignoring either of these in the model would lead to larger errors. Most notably,
      the nonlinearities generated in the water can enhance the focal temperature by
      more than 100%. The simulations also demonstrated that pulsed high power
      sonications may provide an opportunity to significantly (up to a factor of 3)
      reduce the treatment time. In conclusion, nonlinear propagation can play an
      important role in shaping the energy distribution during a focused ultrasound
      treatment and it should not be ignored in planning. However, the current
      simulation methods are accurate only with relatively large F-numbers and better
      models need to be developed for sharply focused transducers.

PMID- 19740626
TI  - Pharmacokinetics of topiramate during pregnancy.
AB  - PURPOSE: To study the effects of pregnancy on plasma concentrations of topiramate
      (TPM). METHODS: An established routine fluorescence polarization immunoassay
      (FPIA) method was used to determine TPM concentrations in 15 women with epilepsy
      treated with TPM during altogether 17 pregnancies. RESULTS: In 10 pregnancies,
      where samples were available from all three trimesters, the mean TPM
      dose/concentration ratio (D/C-ratio) was significantly higher than outside
      pregnancy baseline value 37.3 L/day (+/-15.9), during the 2nd, 67.5L/day (+/
      23.4), and the 3rd trimester, 65.1L/day (+/-30.4), but not during the 1st, 49.4
      L/day (+/-29.4). Including seven additional pregnancies enrolled late with data
      only from the 3rd trimester, the mean D/C-ratio during the 3rd trimester was 67.4
      L/day (+/-27.5) compared to baseline, 38.8L/day (+/-18.0), an average increase by
      71.8%. There was a pronounced intra-individual variability in alterations in D/C
      ratios during pregnancies. CONCLUSIONS: Our data show a significant pregnancy
      related increase in D/C-ratios of TPM suggesting that therapeutic drug monitoring
      might be of value.

PMID- 19740627
TI  - Cultured human melanocytes express functional toll-like receptors 2-4, 7 and 9.
AB  - BACKGROUND: Toll-like receptors (TLRs) recognize pathogen-associated molecular
      patterns (PAMPs), which have been evolutionarily conserved in microbes. Human
      melanocytes are not simply pigment-producing cells but also have the phagocytic
      capacity and can produce pro-inflammatory mediators. However, the mechanisms of
      recognition of microbes by melanocytes have not yet been fully established.
      OBJECTIVE: We investigated the TLRs 1-10 expression profile in human epidermal
      melanocytes and assessed their functions after triggering by their specific
      ligands. METHODS: TLRs mRNA expression was determined by RT-PCR, and the TLR
      protein expression was measured by flow cytometry and immunofluorescence assays.
      After stimulation with various TLR ligands, the production of inflammatory
      cytokine IL-8 and IL-6 was measured by ELISA and the mRNA for chemokine CCL2,
      CCL3 and CCL5 was analyzed by real-time PCR. Phosphorylation of IkappaBalpha in
      TLR ligands-triggered melanocytes was determined by Western blot and the nucleus
      translocation of NF-kappaBp65 was analyzed by immunofluorescence. RESULTS: Human
      melanocytes constitutively expressed TLRs 1-4, 6, 7 and 9 mRNA. Ample amounts of
      TLRs 2-4, 7 and 9 were confirmed at protein level. Stimulation of melanocytes
      with TLRs ligands resulted in the release of cytokines (IL-8 and IL-6) and the
      mRNA accumulation of chemokines (CCL2, CCL3 and CCL5). Triggering of TLRs in
      melanocytes resulted in the up-regulation of phosphorylated IkappaBalpha and in
      the nucleus translocation of NF-kappaBp65. CONCLUSION: Present study indicates
      human melanocytes express a panel of functional TLRs. The ligation of TLRs can
      turn these cells into active players of the skin innate immunity.

PMID- 19740628
TI  - Impact of early appropriate antimicrobial therapy on survival in Acinetobacter
      baumannii bloodstream infections.
AB  - The impact of appropriate empirical antimicrobial therapy for Acinetobacter
      baumannii bacteraemia on patient outcomes has not been clearly established. We
      assessed predictors of 30-day mortality and the effect of inappropriate empirical
      antimicrobial treatment on mortality among patients with A. baumannii bacteraemia
      between July 2005 and June 2008. Initial empirical antimicrobial therapy was
      considered to be appropriate if the initial antibiotics that were administered
      within 48 h after the acquisition of a blood culture sample included at least one
      antibiotic that was active in vitro and when the dosage and route of
      administration were in accordance with current medical standards. Overall, 103
      patients with nosocomial A. baumannii bacteraemia were included in the study.
      Appropriate empirical therapy was administered to 41.7% of patients within 48 h.
      The overall mortality rate was 54.4%, with rates of 39.5% and 65% for patients
      who received appropriate and inappropriate antimicrobial therapy within 48 h,
      respectively. Thus, a 25.5% reduction in the overall crude mortality rate was
      associated with adequate early empirical antimicrobial therapy. Multivariate
      analysis using a Cox regression model showed that significant independent risk
      factors for mortality were delayed appropriate treatment [hazard ratio (HR)=2.4,
      95% confidence interval (CI) 1.3-4.2; P=0.004], development of septic shock
      (HR=2.6, 95% CI 1.4-4.8; P=0.004), age>65 years (HR=2.1, 95% CI 1.2-3.7; P=0.007)
      and mechanical ventilation (HR=3.3, 95% CI 1.5-7.4; P=0.003). It is concluded
      that a delay in receiving appropriate antimicrobial therapy had an adverse
      influence on clinical outcome in patients with A. baumannii bacteraemia.

PMID- 19740629
TI  - The role of efflux pumps in macrolide resistance in Mycobacterium avium complex.
AB  - Mycobacteriumavium complex (MAC) is clinically important since it can cause
      severe infections in acquired immune deficiency syndrome (AIDS) patients and
      other immunocompromised individuals. Use of the macrolides clarithromycin and
      azithromycin has improved the outcome of MAC infections, but therapeutic failure
      is still a major problem. In this work, we studied efflux pump activity in MAC
      clinical strains and evaluated the contribution of active efflux to macrolide
      resistance. Eighteen clinical strains isolated from AIDS patients were evaluated
      for macrolide resistance in the presence and absence of the efflux pump
      inhibitors (EPIs) thioridazine, chlorpromazine and verapamil. The efflux activity
      of these strains was then assessed by a semi-automated fluorometric method that
      detects extrusion of ethidium bromide (EtBr), a known efflux pump substrate.
      Resistance to clarithromycin was significantly reduced in the presence of
      thioridazine, chlorpromazine and verapamil. The same EPIs were effective in
      decreasing the efflux of EtBr from MAC cells. Moreover, increased retention of
      [(14)C]-erythromycin in the presence of these EPIs further demonstrated that
      active efflux contributes to MAC resistance to macrolides. This study
      demonstrates that efflux pumps play an important role in MAC resistance to
      antibiotics.

PMID- 19740630
TI  - Signs of striatal dopamine transporter density increase in association with
      improvement of tardive dyskinesia in a patient with schizophrenia, as
      demonstrated by a DAT scan.
AB  - The imaging of the dopamine transporter could demonstrate the implication of
      dopaminergic pathway in the appearance of tardive dyskinesia. We report a case
      with psychotic and tardive dyskinesia symptoms. A DAT scan showed decreased
      dopamine transporter uptake in the area of brain's basal gaglia. A trial with
      quetiapine improved both psychotic and TD symptoms while a second DAT scan showed
      improvement status. We conclude that increased dopamine transporter uptake seemed
      to associate with the improvement of TD.

PMID- 19740631
TI  - Effect of O/S/W process parameters on 17beta-EV loaded nanoparticles properties.
AB  - ABA triblock copolymer, poly(ethylene glycol)-poly(butylene adipate)
      poly(ethylene glycol) (PEG-PBA-PEG) could form micelle-like nanoparticles due to
      their amphiphilic characteristic. The mechanism of nanoparticle formation is
      based on the modified oil in water (O/W) emulsion by emulsifying acetone solution
      of copolymer containing different amount of dissolved 17beta-estradiol valerate
      (17beta-EV) in olive oil into the external water phase i.e. oil(1) and oil(2) in
      water (O & O/W). The acetone-evaporated nanodroplets involved an inner oil phase,
      an outer water phase and a solid shell between two phases, so called O/S/W
      nanocapsules. In order to control the nanocapsules size, the effect of various
      emulsion parameters such as the concentration of polymer, drug content,
      polymer/oil weight ratio and concentration of surfactant on morphology were
      studied. Particle size, their distribution and release profile of nanocapsules
      were investigated too. This study gave some important information about the
      structure, mechanism of formation, release profile and the physical properties
      (i.e. encapsulation efficiency, drug loading, nanoparticles yield) of
      nanocapsules. To investigate the influence of PEG chain on the stability of
      produced nanodroplets, nanocapsules were also prepared with and without Tween 80
      as surfactant.

PMID- 19740632
TI  - Formulation and physicochemical characterization of poly(epsilon-caprolactone)
      nanoparticles loaded with ftorafur and diclofenac sodium.
AB  - Even though conventional pharmacotherapy has been demonstrated to display very
      efficient activity against a wide variety of diseases, several active agents
      (e.g., anti-tumor drugs and non-steroidal anti-inflammatory drugs) are generally
      needed to be administered at high doses to elicit the required therapeutic
      action, simultaneously leading to severe side effects. This fact is usually due
      to unfavourable pharmacokinetic profiles (poor biological half-life) and to the
      possibility of induction of resistance. In order to increase the therapeutic
      activity of ftorafur and diclofenac sodium along with an overcome of their
      important drawbacks, we investigated their formulation into a colloidal carrier
      based on the biodegradable polymer poly(epsilon-caprolactone). Two drug loading
      methods were studied: (i) surface adsorption in already formed nanoparticles
      after incubation in a drug solution; (ii) drug addition before interfacial
      polymer disposition leading to drug entrapment into the polymeric network. We
      hypothesized that such nanocarrier possessed very significant characteristics
      (e.g., unusually high drug loading and low burst release), suggesting their
      potential application for efficient drug delivery to targeted sites.

PMID- 19740633
TI  - A sensitive DNA biosensor fabricated with gold nanoparticles/poly (p-aminobenzoic
      acid)/carbon nanotubes modified electrode.
AB  - In this work, we fabricated a sensitive electrochemical DNA biosensor for the
      detection of target DNA. Aminobenzoic acid (ABA) was firstly electropolymerized
      on the surface of the glassy carbon electrode (GCE) modified with multi-walled
      carbon nanotubes with carboxyl groups (MWCNTs) by cyclic voltammetry (CV). Gold
      nanoparticles (AuNPs) were subsequently introduced to the surface of PABA-MWNTs
      composite film by electrochemical deposition mode. Probe DNA was immobilized on
      the surface of AuNPs through Au-S bond. Scanning electron microscopy (SEM),
      cyclic voltammetry (CV) and electrochemical impedance spectra (EIS) were used to
      investigate the film assembly process. Differential pulse voltammetry (DPV) was
      used to monitor DNA hybridization event by measurement of the intercalated
      adriamycin. Under the optimal conditions, the increase of reduction peak current
      of adriamycin was linear with the logarithm of the concentration of the
      complementary oligonucleotides from 1.0 x 10(-12) to 5.0 x 10(-9)M with a
      detection limit of 3.5 x 10(-13)M. This DNA biosensor has a good stability and
      reproducibility.

PMID- 19740634
TI  - Hyaluronic acid and chitosan-DNA complex multilayered thin film as surface
      mediated nonviral gene delivery system.
AB  - Sustained release of DNA from the surface of materials represents a promising
      approach to combine the gene therapy and implantable biomaterials. The nonviral
      chitosan-DNA complexes were incorporated into the multilayer via layer-by-layer
      deposition with hyaluronic acid (HA). The UV-vis spectroscopy and atomic force
      microscopy (AFM) results showed the successful construction of the nonviral
      complex contained multilayers. The complexes were releasable in physiological
      condition and a sustained release manner was gained when the multilayer was
      crosslinked. The cell viability test and the gene transfection assay showed that
      the natural polyelectrolyte-based nonviral complex incorporated multilayer not
      only had good cytocompatibility, but also possessed the in vitro gene
      transfection ability. This kind of surface-mediated nonviral complex incorporated
      multilayer may have great potential in the localized and controlled delivery of
      DNA in biomedical implants and tissue engineering application.

PMID- 19740636
TI  - [Antidepressant use in children and adolescents].
AB  - Relative to placebo, selective serotonin reuptake inhibitors (SSRI) are
      efficacious for paediatric affective disorders, although their clinical effects
      appear relatively modest in major depressive disorder, intermediate in obsessive
      compulsive disorder, and stronger in anxiety disorders. If SSRIs modestly
      increase the risk of occurrence of suicidal ideation and behavior, several
      studies show that their use is associated with a significant decrease in the
      suicide rates in children and adolescents, probably because of their efficacy,
      compliance, and low toxicity in overdose.

PMID- 19740635
TI  - Inhibition of anti-fluorescent probe monoclonal antibody by long-chain
      amphiphiles.
AB  - Inhibitions of amphiphiles with a long chain (alcohols with carbon number of 10,
      12, 14, 16 and the corresponding fatty acids) on the antigen-antibody reaction
      between fluorescent probe (fluorescein (FL)) and anti-fluorescent probe
      monoclonal antibody (immunoglobulin G (IgG)-49) were investigated by fluorescence
      spectroscopy. The resulting inhibition modes were compared with those of specific
      inhibitors, 5- and 6-aminofluoresceins (5- and 6-FLNH(2)). In the presence of all
      inhibitors, the fluorescence quenching of FL as the result of inhibitor binding
      to IgG-49 was hindered in an inhibitor concentration-dependent manner. The values
      of IC(50) and Hill number for the inhibitors were determined from dose-response
      curves of the quenching inhibition. The IC(50) values of the alcohols were much
      more dependent on the chain length than those of the fatty acids although all the
      values were in orders of microM. The Hill numbers of both kinds of inhibitors
      became larger values than 1, but they had different values for a series of
      alcohols and fatty acids, respectively. By contrast, the IC(50) values of 5- and
      6-FLNH(2) were in orders of nM and the Hill numbers became smaller values than 1.
      Since the Lineweaver-Burk plots produced an intersection point on the intercept
      of the X-axis for the long-chain inhibitors with carbon number of 14 while did
      that on the intercept of the Y-axis for 6-FLNH(2), respectively, we judged the
      inhibition modes of the former as non-competitive ones and those of the latter as
      a competitive one. Further, the effect of pressure on the inhibition by C(14)OH,
      C(13)COOH and 5-FLNH(2) was examined, and the standard volume changes of IgG-49
      for the inhibitor binding were calculated from the Johnson-Eyring plots. The
      volume change for 5-FLNH(2) was smaller than those for C(14)OH and C(13)COOH
      although they became all negative. This suggests that the volume of IgG-49
      shrinks by the addition of these inhibitors, and IgG-49 is not relevant to a
      model protein for the molecular mechanism of anesthesia.

PMID- 19740637
TI  - An assessment of action levels in imaging strategies in head and neck cancer
      using TomoTherapy. Are our margins adequate in the absence of image guidance?
AB  - AIMS: To assess the effectiveness of different on-treatment correction strategies
      on set-up accuracy in patients with head and neck cancer (HNC) treated on a
      TomoTherapy HiArt system. To assess the adequacy of clinical target volume (CTV)
      to planning target volume (PTV) treatment planning margins when treating with
      intensity-modulated radiotherapy without daily image guidance. MATERIALS AND
      METHODS: The set-up accuracy measured by daily online volumetric imaging was
      retrospectively reviewed for the first 15 patients with HNC treated on the
      TomoTherapy unit at Addenbrooke's Hospital. For each fraction, megavoltage
      computed tomography was carried out, any discrepancy from the planning scan was
      noted, and corrected, before treatment. These data were used to evaluate imaging
      correction protocols using three different action levels. The first three
      fractions were imaged and used to correct for systematic error, using a 5 mm
      action level (5 mmAL), a 3 mm action level (3 mmAL), and no action level (NAL).
      All imaging strategies were applied, to assess the number of fractions that would
      potentially have exceeded a 5 and 3 mm margin. Systematic and random errors were
      calculated for the population, assuming the NAL protocol had been applied, and
      minimum CTV-PTV margins, required to allow for errors attributable only to set
      up, were calculated using van Herk's formula. RESULTS: In total, 490 fractions
      were analysed. Using a 5 mmAL imaging protocol, potentially 198/490 fractions
      (40%) were outside a 5 mm CTV-PTV margin and 400/490 (82%) were outside a 3 mm
      margin. Using a 3 mmAL imaging protocol, potentially 67/490 fractions (14%) were
      outside a 5 mm CTV-PTV margin and 253/490 (52%) were outside a 3 mm margin. A
      small systematic error was identified in the system; once corrected this would
      improve these results. Using the NAL imaging protocol, potentially 31/490
      fractions (6%) were outside a 5 mm CTV-PTV margin and 143/490 fractions (29%)
      were outside a 3 mm margin. Estimated minimum CTV-PTV margins to account only for
      set-up errors, with three-fraction image-guided radiotherapy and a NAL protocol,
      were 2.8, 3.1 and 4.1 mm in the mediolateral, superior-inferior and anterior
      posterior directions, respectively. CONCLUSION: Reducing the action level at
      which the systematic error is corrected improves the probability of treatment
      delivery accuracy. Using the NAL correction protocol reduces the number of
      fractions that have set-up displacements outside a 5 mm CTV-PTV margin. Although
      a 5 mm margin is probably sufficient for standard HNC radiotherapy, change to a 3
      mm margin is not favoured at our centre without access to daily image-guided
      radiotherapy.

PMID- 19740638
TI  - Peroxisomes and peroxisomal disorders: the main facts.
AB  - The importance of peroxisomes for human health is highlighted by the number of
      peroxisomal disorders (PDs), diseases associated to peroxisome biogenesis
      disorders and peroxisomal enzyme/transporter deficiencies. Currently, many
      physiological/biosynthetic mechanisms involved in these illnesses have been
      elucidated, but PDs remain incurable. This review examines the most important
      aspects concerning peroxisomes (i.e. peroxisome proliferation, peroxisome
      biogenesis, metabolic functions of mammalian peroxisomes) and presents the most
      significant trends and advances in the study of peroxisomal disorders.

PMID- 19740639
TI  - Isolation and characterization of a French bean hemagglutinin with antitumor,
      antifungal, and anti-HIV-1 reverse transcriptase activities and an exceptionally
      high yield.
AB  - A dimeric 64-kDa hemagglutinin was isolated with a high yield from dried
      Phaseolus vulgaris cultivar "French bean number 35" seeds using a chromatographic
      protocol that involved Blue-Sepharose, Q-Sepharose, and Superdex 75. The yield
      was exceptionally high (1.1g hemagglutinin per 100g seed), which is around 10-85
      times higher than other Phaseolus cultivars. Its N-terminal sequence resembled
      those of other Phaseolus hemagglutinins. The hemagglutinating activity of the
      hemagglutinin was stable in the pH range 6-8, and in the temperature range 0
      degrees C-50 degrees C. It inhibited HIV-1 reverse transcriptase with an IC50 of
      2microM. It suppressed mycelial growth in Valsa mali with an IC50 of 10microM. It
      inhibited proliferation of hepatoma HepG2 cells and breast cancer MCF-7 cells
      with an IC50 of 100 and 2microM, respectively. It had no antiproliferative effect
      on normal embryonic liver WRL68 cells.

PMID- 19740640
TI  - Cytoskeletal control of growth and cell fate switching.
AB  - Living cells must be able to switch between growth and differentiation with high
      fidelity and precise spatial control to ensure that normal tissue patterns are
      formed in the embryo and maintained throughout adult life. Most work on cell
      proliferation focuses on elucidating the signaling pathways responsible for
      control of cell cycle progression that are triggered by cell binding to soluble
      growth factors and insoluble extracellular matrix. Here we review recent work,
      which has revealed that mechanical tension-dependent changes in cell shape and
      cytoskeletal structure are equally critical for control of growth, as well as
      cell fate switching. This interplay between soluble, insoluble, and mechanical
      cues helps to explain how cell behaviors responsible for tissue formation are
      controlled in the physical context of living tissues.

PMID- 19740641
TI  - Caffeic acid phenethyl ester is a potent inhibitor of HIF prolyl hydroxylase:
      structural analysis and pharmacological implication.
AB  - Caffeic acid phenethyl ester (CAPE) is an active component of propolis from
      honeybee. We investigated a potential molecular mechanism underlying a CAPE
      mediated protective effect against ischemia/reperfusion (I/R) injury and analyzed
      the structure contributing to the CAPE effect. CAPE induced hypoxia-inducible
      factor-1 (HIF-1) alpha protein, concomitantly transactivating the HIF-1 target
      genes vascular endothelial growth factor and heme oxygenase-1, which play a
      protective role in I/R injury. CAPE delayed the degradation of HIF-1alpha protein
      in cells, which occurred by inhibition of HIF prolyl hydroxylase (HPH), the key
      enzyme for von Hippel-Lindau-dependent HIF-1alpha degradation. CAPE inhibition of
      HPH and induction of HIF-1alpha protein were neutralized by an elevated dose of
      iron. The catechol moiety, a chelating group, is essential for HPH inhibition,
      while hydrogenation of the double bond (-C=C-) in the Michael reaction acceptor
      markedly reduced potency. Removal of the phenethyl moiety of CAPE (substitution
      with the methyl moiety) severely deteriorated its inhibitory activity for HPH.
      Our data suggest that a beneficial effect of CAPE on I/R injury may be ascribed
      to the activation of HIF-1 pathway via inhibition of HPH and reveal that the
      chelating moiety of CAPE acted as a pharmacophore while the double bond and
      phenethyl moiety assisted in inhibiting HPH.

PMID- 19740642
TI  - Factors influencing waste separation and utilization among households in the Lake
      Victoria crescent, Uganda.
AB  - Wastes, which are the by-products of consumption, are a growing problem in the
      urban and peri-urban areas of the Lake Victoria region largely due to high urban
      population growth rates, consumption habits, low collection rates and hence waste
      accumulation. Whereas the biodegradable proportion is high and could be
      reutilized, a few have tapped the economic potential of this waste. This study
      was conducted to explore the potential alternatives and determinants of waste
      separation and utilization among urban and peri-urban households in the Lake
      Victoria crescent. A random sample of households in five urban and peri-urban
      areas of the crescent were selected and surveyed. Logit models were used to
      establish the factors influencing waste separation and utilization in urban and
      peri-urban areas of the lake crescent. Results indicate that, gender, peer
      influence, land size, location of household and membership of environmental
      organization explain household waste utilization and separation behaviour.
      Campaigns for waste separation and reuse should be focused in the peri-urban
      areas where high volumes of wastes are generated and accumulate. Social influence
      or pressure should be used to encourage more waste reuse and separation.

PMID- 19740643
TI  - Bio-based composites from waste agricultural residues.
AB  - The main objective of this research was to study the potential of waste
      agricultural residues such as sunflower stalk, corn stalk and bagasse fibers as
      reinforcement for thermoplastics as an alternative to wood fibers. The effects of
      two grades (Eastman G-3003 and G-3216) of coupling agents on the mechanical
      properties were also studied. In the sample preparation, one level of fiber
      loading (30wt.%) and three levels of coupling agent content (0, 1.5 and 2.5wt.%)
      were used. For overall trend, with addition of both grades of the coupling
      agents, tensile, flexural and impact properties of the composites significantly
      improved, as compared with untreated samples. In addition, morphological study
      revealed that the positive effect of coupling agent on interfacial bonding. The
      composites treated with G-3216 gave better results in comparison with G-3003.
      This could be caused by the high melt viscosity of G-3003. In general, bagasse
      fiber showed superior mechanical properties due to its chemical characteristics.

PMID- 19740644
TI  - Dechlorination/detoxification of aromatic chlorides using fly ash under mild
      conditions.
AB  - An efficient dechlorination/detroxification method for p-nitrochlorobenzene, p
      chloroanisole and 1-chloronaphthalene on municipal waste incinerator fly ash in
      presence of reducing agents with water/alcohol mixtures was developed.
      Dechlorination% was higher in water/isopropanol mixture at temperature <100
      degrees C. Metal contents of fly ash played a vital role in enhancing
      dechlorination at low temperature. Moreover, the fly ash particles provided the
      surface to accomplish reduction and substitution reactions by adsorbing the
      chlorinated aromatic compound, hydrogen and hydroxyl ions. The mechanism of
      dechlorination was envisaged.

PMID- 19740645
TI  - DNAzyme-based microarray for highly sensitive determination of metal ions.
AB  - A novel microarray for the multiplex determination of heavy metal ions in aqueous
      solution based on DNAzymes has been developed with good sensitivity and
      selectivity. In the present work, metal ion dependent DNAzymes of copper (Cu-Enz)
      and lead (Pb-Enz) were first associated with their corresponding DNA substrates
      (Cu-Sub and Pb-Sub) immobilized on the surface of aldehyde-coated slides. After
      introducing the corresponding metal ions, the DNA cleavage of the substrates
      caused by the DNAzymes took place, resulting in a dramatic change in fluorescent
      signal intensity. The proposed microarray method, which can be used as a multi
      component assay with high efficiency, combines the high sensitivity and
      selectivity of DNAzymes with the high throughput and parallel analysis of
      microarray technology. The method reveals a sensitivity corresponding to 0.6ppb
      and 2ppb for Cu(2+) and Pb(2+), respectively, which is sufficient to detect them
      in drinking water. This approach may find potential applications in environmental
      monitoring, food safety monitoring, clinical toxicology, waste treatment, the
      cosmetic industry and industrial process monitoring.

PMID- 19740646
TI  - SERS detection of indirect viral DNA capture using colloidal gold and methylene
      blue as a Raman label.
AB  - An indirect capture model assay using colloidal Au nanoparticles is demonstrated
      for surface enhanced Raman scattering (SERS) spectroscopy detection of DNA. The
      sequence targeted for capture was derived from the West Nile Virus (WNV) RNA
      genome and selected on the basis of exhibiting minimal secondary structure
      formation. Upon incubation with colloidal Au, hybridization complexes containing
      the WNV target sequence, a complementary capture oligonucleotide conjugated to a
      strong tethering group and a complementary reporter oligonucleotide conjugated to
      methylene blue (MB), a Raman label, anchors the resultant ternary complex to Au
      nanoparticles and positions MB within the required sensing distance for SERS
      enhancement. The subsequent elicitation of surface enhanced plasmon resonance by
      laser excitation provides a spectral peak signature profile that is capture
      specific and characteristic of the Raman spectrum for MB. Detection sensitivity
      is in the submicromolar range and was shown to be highest for thiol, and less so
      for amino, modifications at the 5' terminus of the capture oligonucleotide.
      Finally, using Quartz Crystal Microbalance-Dissipation as a tool for modeling
      ternary complex binding to Au surfaces, quantitative measurements of surface mass
      coverage on Au plated sensor crystals established a positive correlation between
      levels of ternary complex adsorption and their correspondent levels of SERS
      signal intensification. Adapted to a compact Raman spectrometer, which is
      designed for analyte detection in capillary tubes, this assay provides a rapid,
      mobile and cost effective alternative to expensive spectroscopic instrumentation,
      which is often restricted to analytical laboratories.

PMID- 19740647
TI  - Poly(brilliant cresyl blue)-carbonnanotube modified electrodes for determination
      of NADH and fabrication of ethanol dehydrogenase-based biosensor.
AB  - A single walled-carbon nanotube (SWNT) modified with poly brilliant cresyl blue
      (PBCB) glassy carbon electrode has been fabricated by a simple, method in order
      to facilitate electrocatalytic detection of NADH. At this chemically modified
      electrode, NADH was determined in neutral phosphate buffer solution at 0V (vs.
      SCE). The amperometric detection provided a wide linear current vs. concentration
      range (3.0-104.2 microM), a fast response time (within 5s), high sensitivity
      [9.89nA (muM)(-1)] and a low detection limit (1.0 microM, S/N=3). No interference
      was observed with a 100-fold excess of dopamine or uric acid. An ethanol
      biosensor also was developed using the nanocomposite modified electrode, by
      immobilizing ethanol dehydrogenase with carrageenan. In this case a linear
      ethanol concentration response was achieved in the range from 0.4 to 2.4mM and
      the detection limit was estimated to be 0.1mM (S/N=3). The analytical performance
      achieved with the of the PBCB/SWNT nanocomposite electrode is expected to the
      development of novel biosensors, biofuel cells, and other bioelectrochemical
      devices.

PMID- 19740648
TI  - Genetic dissection of myelinated axons in zebrafish.
AB  - In the vertebrate nervous system, the myelin sheath allows for rapid and
      efficient conduction of action potentials along axons. Despite the essential
      function of myelin, many questions remain unanswered about the mechanisms that
      govern the development of myelinated axons. The fundamental properties of myelin
      are widely shared among vertebrates, and the zebrafish has emerged as a powerful
      system to study myelination in vivo. This review will highlight recent advances
      from genetic screens in zebrafish, including the discovery of the role of kif1b
      in mRNA localization in myelinating oligodendrocytes.

PMID- 19740650
TI  - Industrial harvesting of olive tree pruning residue for energy biomass.
AB  - In Mediterranean countries, olive tree pruning residue represents an abundant
      source of energy biomass, still largely unexploited for lack of cost-effective
      harvesting technology. The authors tested two industrial pruning harvesters,
      capable of overcoming the limits of lighter units appeared in the past years. One
      of the machines was designed for application to a powerful farm tractor, whereas
      the other was a self-propelled dedicated harvester. Data were collected from 10
      operations, covering a total of 69 hectares and producing over 190 tonnes of wood
      fuel. Recorded productivity varied between 3 and 9 tonnes per scheduled machine
      hour (SMH), or 2-7 oven dry tonnes (odt) SMH(-1). Harvesting cost varied from 17
      to 52 euro t(-1), with an average value of 28 euro t(-1): these values
      correspond, respectively to 22, 70 and 40 euro odt(-1). This compares very
      favourably with the average 1-1.5 ton SMH(-1) offered by lighter commercial
      units. Productivity was related to residue density, row length and forwarding
      distance. Mechanical availability was high and over 90%, for both machines. The
      authors also developed a simple deterministic model capable of predicting
      harvesting productivity and cost, as a function of significant site and economic
      conditions. The model can also be used to determine the break-even utilization
      level, below which the operational flexibility of a tractor-mounted operation
      becomes preferable to the higher productivity of a specialised unit.

PMID- 19740651
TI  - Modeling of copper fixed-bed biosorption from wastewater by Posidonia oceanica.
AB  - Biosorption of copper from aqueous solutions by Posidonia oceanica was
      investigated in batch and fixed-bed experiments. Batch experiments were conducted
      to evaluate the removal equilibrium at pH 5.0 and 6.0; experimental data were
      fitted to Langmuir model with maximum uptake capacities of 56.92 and 85.78 mg g(
      1), respectively. Five column experiments were carried out at different feed
      concentrations. Breakthrough times and continuous sorption isotherm were obtained
      from breakthrough curves. Differences among batch and continuous isotherms were
      observed; the maximum uptake capacity in dynamic conditions was found in 56.70 mg
      g(-1) for final pH between 5.0 and 5.5. The biosorbent was regenerated with HCl.
      Hydrodynamic axial dispersion was estimated by tracing experiments at different
      velocities using LiCl as tracer. A mass transport model including convection
      dispersion and sorption processes was successfully applied to breakthrough curve
      modeling. Results indicate that P. oceanica can be used as an effective
      biosorbent for copper removal.

PMID- 19740649
TI  - Two-tier transcriptional control of oligodendrocyte differentiation.
AB  - Oligodendrocytes (OLs) are the myelin-forming cells of the central nervous system
      (CNS). They differentiate from proliferative OL precursor cells that migrate from
      the embryonic neuroepithelium throughout the developing CNS before associating
      with axons and elaborating myelin. Recent research into the regulation of OL
      differentiation has uncovered a two-stage mechanism of transcriptional control
      that combines epigenetic repression of transcriptional inhibitors with direct
      transcriptional activation of myelin genes. This 'two-pronged' approach creates a
      fail-safe system of genetic control to ensure orderly and unambiguous expression
      of the myelination program during development and during repair of demyelinated
      lesions.

PMID- 19740652
TI  - Subcritical water liquefaction of oil palm fruit press fiber for the production
      of bio-oil: effect of catalysts.
AB  - Decomposition of oil palm fruit press fiber (FPF) to various liquid products in
      subcritical water was investigated using a high-pressure autoclave reactor with
      and without the presence of catalyst. When the reaction was carried in the
      absence of catalyst, the conversion of solid to liquid products increased from
      54.9% at 483 K to 75.8% at 603 K. Simultaneously, the liquid yield increased from
      28.8% to 39.1%. The liquid products were sub-categorized to bio-oil (benzene
      soluble, diethylether soluble, acetone soluble) and water soluble. When 10%
      ZnCl(2) was added, the conversion increased slightly but gaseous products
      increased significantly. However, when 10% Na(2)CO(3) and 10% NaOH were added
      independently, the solid conversion increased to almost 90%. In the presence of
      catalyst, the liquid products were mainly bio-oil compounds. Although solid
      conversion increased at higher reaction temperature, but the liquid yield did not
      increase at higher temperature.

PMID- 19740653
TI  - Evaluation of alkyl esters from Camelina sativa oil as biodiesel and as blend
      components in ultra low-sulfur diesel fuel.
AB  - Methyl and ethyl esters were prepared from camelina [Camelina sativa (L.) Crantz]
      oil by homogenous base-catalyzed transesterification for evaluation as biodiesel
      fuels. Camelina oil contained high percentages of linolenic (32.6 wt.%), linoleic
      (19.6 wt.%), and oleic (18.6 wt.%) acids. Consequently, camelina oil methyl and
      ethyl esters (CSME and CSEE) exhibited poor oxidative stabilities and high iodine
      values versus methyl esters prepared from canola, palm, and soybean oils (CME,
      PME, and SME). Other fuel properties of CSME and CSEE were similar to CME, PME,
      and SME, such as low temperature operability, acid value, cetane number,
      kinematic viscosity, lubricity, sulfur and phosphorous contents, as well as
      surface tension. As blend components in ultra low-sulfur diesel fuel, CSME and
      CSEE were essentially indistinguishable from SME and soybean oil ethyl ester
      blends with regard to low temperature operability, kinematic viscosity,
      lubricity, and surface tension.

PMID- 19740654
TI  - Amiodarone and its putative metabolites fail to activate wild type hTAAR1.
AB  - The ability of amiodarone and its putative metabolites to activate unmodified
      human trace amine associated receptor 1 (hTAAR1) stably expressed in CHO cell
      lines was evaluated. Receptor activation was monitored by measuring the
      accumulation of cAMP, the putative hTAAR1 native second messenger, or calcium
      mobilization in cells where the receptor was coupled to the promiscuous Gq,
      Galpha16. Despite literature reports of activation of rodent TAAR1 by these
      agents, no response was seen in either cell line although robust activation was
      obtained with the endogenous ligand beta-phenethylamine. These results indicate
      that TAAR1 activation by amiodarone and its analogs is species specific.

PMID- 19740655
TI  - Diastereoisomers of 2-benzyl-2, 3-dihydro-2-(1H-inden-2-yl)-1H-inden-1-ol:
      potential anti-inflammatory agents.
AB  - The synthesis and biological activity of the novel diastereoisomers of 2-benzyl
      2,3-dihydro-2-(1H-inden-2-yl)-1H-inden-1-ol is reported. The 2,2-coupled indane
      dimers were synthesised by coupling of the silyl enol ether of 1-indanone with
      the dimethyl ketal of 2-indanone. The coupled product was directly alkylated to
      give the racemic ketone which was reduced to the diastereoisomeric alcohols. The
      alcohols were separated and their relative stereochemistry was established by X
      ray crystallography. These molecules demonstrate significant anti-inflammatory
      activity in vivo and in vitro and may represent a new class of anti-inflammatory
      agent.

PMID- 19740656
TI  - Parallel chemoenzymatic synthesis of sialosides containing a C5-diversified
      sialic acid.
AB  - A convenient chemoenzymatic strategy for synthesizing sialosides containing a C5
      diversified sialic acid was developed. The alpha2,3- and alpha2,6-linked
      sialosides containing a 5-azido neuraminic acid synthesized by a highly efficient
      one-pot three-enzyme approach were converted to C5''-amino sialosides, which were
      used as common intermediates for chemical parallel synthesis to quickly generate
      a series of sialosides containing various sialic acid forms.

PMID- 19740657
TI  - Imidazo[1,5-a][1,2,4]-triazolo[1,5-d][1,4]benzodiazepines as potent and highly
      selective GABAA alpha5 inverse agonists with potential for the treatment of
      cognitive dysfunction.
AB  - In a search for GABAA alpha5 ligands that combine high subtype binding
      selectivity with a marked inverse agonism imidazo[1,5-a][1,2,4]-triazolo[1,5
      d][1,4]benzodiazepines were identified as a promising class. A short tandem
      reaction allowed rapid access to this chemical series, thereby facilitating rapid
      SAR generation which guided the optimization process. Two compounds (10e and 11f)
      were found to be active in an in vivo paradigm for cognitive improvement.

PMID- 19740658
TI  - Design and optimisation of selective serotonin re-uptake inhibitors with high
      synthetic accessibility: part 2.
AB  - A second wave of potential SSRIs with high ease of synthetic accessibility were
      designed based on the reported selective serotonin re-uptake inhibitor litoxetine
      and our own previous work in this area. Preparation and subsequent optimisation
      yielded a range of potent and highly selective SSRIs.

PMID- 19740659
TI  - Potent biphenyl- and 3-phenyl pyridine-based inhibitors of acetyl-CoA
      carboxylase.
AB  - We report the synthesis and enzymatic evaluation of potent inhibitors of acetyl
      CoA carboxylases (ACCs) containing biphenyl or 3-phenyl pyridine cores. These
      compounds inhibit both ACC1 and ACC2, or are moderately selective for either
      enzyme, depending on side chain substitution. Typical activities of the most
      potent compounds in this class are in the low double-digit to single-digit
      nanomolar range in in vitro assays using human ACC1 and ACC2 enzymes.

PMID- 19740660
TI  - Synthesis and evaluation of 9-aminoacridines derived from benzyne click
      chemistry.
AB  - A small set of 9-aminoacridine-3- and 4-carboxamides were synthesized efficiently
      using the benzyne/azide click chemistry. The products bind to duplex DNA but have
      different antitumour activity in the HL60 cell line.

PMID- 19740661
TI  - Spatial and temporal gait parameters in Alzheimer's disease and aging.
AB  - Spatial and temporal gait parameters in 40 patients with early Alzheimer's
      disease (AD) were compared to that of 34 normal controls (NC) on a level ground
      and on a treadmill. Over-ground velocity, cycle-time, cadence, stride-length,
      stride-width and double-support time were captured on an electronic walkway. On
      the treadmill, cadence, cycle-time and double-support time were recorded at a
      preferred velocity using footswitches. The AD group were significantly slower on
      the Timed Up and Go task compared to NC (p<0.05). AD patients differed
      significantly from the NC on their over-ground gait velocity (99+/-19 cm/s vs
      119+15 cm/s, p<0.001), cadence (101+/-9 steps/min vs 109+/-9 steps/min, p=0.001)
      and stride-length (118+/-18 cm vs 131+/-17 cm, p<0.01). On the treadmill, only
      preferred speed was significantly different in the AD group compared to the NC
      group (60+/-20 cm/s vs 74+/-23 cm/s, p=0.02). These results indicate that
      patients with early AD walk slower and with shorter strides than healthy older
      adults.

PMID- 19740662
TI  - The prognostic value of speech recognition scores at diagnosis of vestibular
      schwannoma.
AB  - We aimed to assess whether speech recognition scores (SRS) are predictive of
      outcomes in patients with small vestibular schwannoma (VS) undergoing
      observation. Ninety-five patients with VS whose initial management was
      observation with serial imaging were retrospectively analysed. Patients were
      divided into groups according to their average hearing level and SRS at
      diagnosis. About 60% of patients had good initial SRS (GIS) and 40% had poor
      initial SRS (PIS). Mean follow-up was 44 months, during which time data were
      collected regarding hearing level, tumour growth and the eventual management
      option (continued or failed observation). Observation was discontinued by 24%
      (23/95) of patients. GIS-patients were more likely to maintain stable hearing
      than those with PIS (p<0.05). Hearing was stable in 73% (64/87) of patients.
      These findings indicate that patients with PIS are more vulnerable to progressive
      hearing loss than those with GIS. Observation may be a suitable management option
      for all patients with small VS, particularly those with GIS.

PMID- 19740664
TI  - Secondary resurfacing of the patella in total knee arthroplasty.
AB  - Anterior knee pain following primary total knee arthroplasty is common and can be
      difficult to treat satisfactorily. We reviewed 28 consecutive patients (29 knees)
      who underwent secondary resurfacing of the patella for persistent anterior knee
      pain and report on the results. Mean follow-up was 28 months (range 12-61) with
      no cases lost to follow-up. Oxford knee scores, range of motion, the patient's
      assessment of outcome and overall satisfaction were recorded. Seventeen out of 19
      (59%) felt their knee was better following patellar resurfacing, 10 out of 29
      (34%) felt it was the same and two out of 29 (7%) felt it was worse. There was a
      significant improvement in Oxford knee scores (p<0.001) and significant increase
      in patient satisfaction (p<0.001) following secondary resurfacing. While
      secondary resurfacing of the patella does not provide the solution for every case
      of anterior knee pain following total knee joint replacement, in greater than 50%
      of cases it can be effective at relieving symptoms and in this series carries a
      low risk of worsening symptoms or complications.

PMID- 19740665
TI  - Repair of the posterior root of the medial meniscus.
AB  - Tears of the posterior root of the medial meniscus are becoming increasingly
      recognized. Early identification and treatment of these tears help halt the
      progression of cartilage degeneration and osteoarthritis of the knee. Repair of
      these tears is essential for recreating the hoop stress of the medial meniscus.
      In this note, we describe a successful arthroscopic technique to repair this
      lesion. A posteromedial portal is established by which two 2-0 PDS sutures are
      placed through the meniscus root and pulled down through a trans-tibial tunnel
      and fixed using an EndoButton distally along the anterolateral cortex of the
      tibia. This has been performed successfully in five patients with no
      complications.

PMID- 19740663
TI  - Post-translational modifications in circadian rhythms.
AB  - The pace has quickened in circadian biology research. In particular, an abundance
      of results focused on post-translational modifications (PTMs) is sharpening our
      view of circadian molecular clockworks. PTMs affect nearly all aspects of clock
      biology; in some cases they are essential for clock function and in others, they
      provide layers of regulatory fine-tuning. Our goal is to review recent advances
      in clock PTMs, help make sense of emerging themes, and spotlight intriguing (and
      perhaps controversial) new findings. We focus on PTMs affecting the core
      functions of eukaryotic clocks, in particular the functionally related
      oscillators in Neurospora crassa, Drosophila melanogaster, and mammalian cells.

PMID- 19740666
TI  - Can pre-operative measures predict quadruple hamstring graft diameter?
AB  - The use of autologous grafts such as the quadrupled semitendinosus and gracilis
      tendon is very common in anterior cruciate ligament (ACL) reconstruction. The
      diameter of such grafts can be variable and thus unpredictable prior to surgery.
      In this study, we hypothesized that parameters such as gender, height, age, and
      body mass index (BMI) can be used pre-operatively to reveal the true graft
      diameter. All hamstring ACL reconstructions from 1994 to 2002 were reviewed. 536
      cases (302 females, 234 males) met the inclusion criteria. Quadruple hamstring
      constructs and femoral tunnel diameters were measured using 1mm increment graft
      sizers. Pre-operative measures of height, weight, body mass index, gender, and
      age were obtained. Multiple regression analysis was used to build a predictive
      model of the quadruple hamstring graft diameter. The results of the study
      demonstrated that males had significantly larger grafts than females (8.1+/-0.8
      vs. 7.5+/-0.6mm). Multiple regression analysis on the entire group showed that
      pre-operative height (p<0.0002) and gender (p<0.0047), but not age (p<0.06) or
      weight (p<0.019) were significant predictors of graft diameter. Height (p<0.0001)
      was a specific predictor solely in men. In females, none of the pre-operative
      measures were predictive of graft diameters. Patient height and gender can be
      used as pre-operative indicators of in vivo quadrupled hamstring graft diameter.
      Regardless of other variables, 42% of females will have tunnel diameters of 7mm
      or less. An alternative graft choice should be discussed pre-operatively if graft
      sizes may be of concern for the tall and large female patients.

PMID- 19740667
TI  - Synthesis and biological evaluation of 2,3,4-triarylbenzopyran derivatives as
      SERM and therapeutic agent for breast cancer.
AB  - A novel class of 2,3,4-triarylbenzopyrans has been synthesized and were evaluated
      for their selective estrogen receptor modulation activity and as a therapeutic
      agent for breast cancer. Among the compounds synthesized, compounds 11a and 12c
      exhibited 73.91% and 69.24% inhibition as estrogen antagonistic activity,
      respectively. Compound 12a showed the lowest IC(50) at 6.97 microM against MCF-7
      and 11f showed the lowest IC(50) value of 5.6 microM against MDA-MB-231 cell line
      in spite of their low receptor binding affinity implicating these compounds
      probably act through ER independent mechanism.

PMID- 19740668
TI  - Inhibition of serotonin and norepinephrine reuptake and inhibition of
      phosphodiesterase by multi-target inhibitors as potential agents for depression.
AB  - Compounds possessing more than one functional activity incorporated into the same
      molecule may have advantages in treating complex disease states. Balanced
      serotonin/norepinephrine reuptake inhibitors (SNRIs) (i.e., (R)- and (S)
      norduloxetine) were chemically linked to a PDE4 inhibitor via a five carbon
      bridge. The new dual SNRI/PDE4 inhibitors (i.e., (R)-15 and (S)-15) showed
      moderately potent serotonin reuptake inhibition (IC(50) values of 442 and 404 nM,
      respectively) but low reuptake inhibition of norepinephrine (IC(50) values of
      2097 and 2190 nM, respectively) in vitro. The dual SNRI/PDE4 inhibitors (i.e.,
      (R)-15 and (S)-15) also inhibited PDE4D2 (i.e., K(i) values of 23 and 45 nM,
      respectively). Due to their synergistic functional activity, SNRI/PDE4 inhibitors
      may be effective in treating diseases such as depression.

PMID- 19740669
TI  - Push-pull benzothiazole derivatives as probes for detecting beta-amyloid plaques
      in Alzheimer's brains.
AB  - We synthesized push-pull benzothiazole derivatives and evaluated their potential
      as beta-amyloid imaging probes. In binding experiments in vitro, the
      benzothiazoles showed excellent affinity for synthetic Abeta(1-42) aggregates.
      beta-Amyloid plaques in the mouse and human brain were clearly visualized with
      the benzothiazoles, reflecting the results in vitro. These compounds may be a
      useful scaffold for the development of novel PET/SPECT and fluorescent tracers
      for detecting beta-amyloid in Alzheimer's brains.

PMID- 19740670
TI  - Rapid isolation of novel FK506 binding proteins from multiple organisms using
      gDNA and cDNA T7 phage display.
AB  - Reverse chemical proteomics using T7 phage display is a powerful technique for
      identifying cellular receptors of biologically active small molecules. However,
      to date this method has generally been limited to cDNA libraries constructed from
      mRNA isolated from eukaryotes. In this paper, we describe the construction of the
      first prokaryotic T7 phage display libraries from randomly digested Pseudomonas
      stutzeri and Vibrio fischeri gDNA, as well as a plant cDNA library from
      Arabidopsis thaliana. We also describe the use of T7 phage display to identify
      novel proteins from environmental DNA samples using biotinylated FK506 as a model
      affinity probe.

PMID- 19740671
TI  - Synthesis and dopaminergic activity of some E-3-(piperidin-1-yl)-1-(4-substituted
      phenyl)prop-2-en-1-one derivatives.
AB  - A convenient route for the synthesis of some 2-propen-1-one derivatives with E
      isomeric configuration is described. The activity of the synthesized compounds
      was evaluated through behavioral studies of apomorphine-induced licking in animal
      models. It was demonstrated that most of the synthesized compounds showed
      moderate activity in inhibition of lickings, among which 6a, was the most active
      compound at 30 mg/kg.

PMID- 19740672
TI  - Simple determination of (99)Tc in radioactive waste using Tc extraction disk and
      imaging plates.
AB  - A simple method was developed for determination of (99)Tc in low-level
      radioactive waste: Technetium-99 retained by a solid phase extraction disk was
      directly measured with imaging plates system. It was found that more than 97% of
      Tc were retained by the disk from a solution of pH 2 to 12, whereas depth profile
      of Tc in the disk, which greatly influences the counting efficiency, depended on
      solution pH. The present method was successfully applied to actual radioactive
      liquid waste samples arising from nuclear research facilities.

PMID- 19740673
TI  - Specific interaction of jacalin with phycocyanin, a fluorescent phycobiliprotein.
AB  - Recent research has shown that, like porphyrins, phycocyanin (PC) too can produce
      singlet oxygen upon excitation with the appropriate radiation and hence could be
      useful in photodynamic therapy (PDT) for cancer. Unlike porphyrins, PC has the
      advantage of being a non-toxic, non-carcinogenic, soluble protein. However, the
      challenge would be to target the fluorescent phycobiliprotein to malignant cells.
      We report here that the tumor-specific lectin, jacalin, binds PC specifically in
      a carbohydrate-independent manner and with affinities better than that for
      porphyrins. Hence the lectin could prove to be a useful carrier for targeted
      delivery of PC. The interaction involves both ionic and hydrophobic interactions
      and more than one contact site.

PMID- 19740674
TI  - The hypothalamic GnRH pulse generator: multiple regulatory mechanisms.
AB  - Pulsatile secretion of gonadotropin-releasing hormone (GnRH) release is an
      intrinsic property of hypothalamic GnRH neurons. Pulse generation has been
      attributed to multiple specific mechanisms, including spontaneous electrical
      activity of GnRH neurons, calcium and cAMP signaling, a GnRH receptor autocrine
      regulatory component, a GnRH concentration-dependent switch in GnRH receptor
      (GnRH-R) coupling to specific G proteins, the expression of G protein-coupled
      receptors (GPCRs) and steroid receptors, and homologous and heterologous
      interactions between cell membrane receptors expressed in GnRH neurons. The
      coexistence of multiple regulatory mechanisms for pulsatile GnRH secretion
      provides a high degree of redundancy in maintaining this crucial component of the
      mammalian reproductive process. These studies provide insights into the basic
      cellular and molecular mechanisms involved in GnRH neuronal function.

PMID- 19740676
TI  - Severe hyperphosphatemia in a newborn with renal insufficiency because of an
      erroneous medical prescription.
AB  - We report on an 8-day-old boy with renal failure attributable to bilateral
      vesicoureteral reflux and dysplastic kidneys. He developed hyperphosphatemia
      because of his oral phosphate intake. Because he had mild metabolic acidosis,
      alkaline therapy was planned, but through a medical prescription error he was
      given a phosphate instead of an alkaline solution. He developed carpopedal spasm,
      with calcium and phosphate at 5.3mg/dL and 26.0mg/dL, respectively. His phosphate
      levels gradually decreased via diuretic and calcium gluconate therapy, without
      dialysis.

PMID- 19740675
TI  - Regulation of JNK and p38 MAPK in the immune system: signal integration,
      propagation and termination.
AB  - Stress-activated MAP kinases (MAPKs), comprised of JNK and p38, play prominent
      roles in the innate and adaptive immune systems. Activation of MAPKs is mediated
      by a three-tiered kinase module comprised of MAPK kinase kinases (MAP3Ks), MAPK
      kinases (MAP2Ks) and MAPKs through sequential protein phosphorylation. Activated
      MAPKs, in turn, phosphorylate transcription factors and other targets to regulate
      gene transcription and immune responses. Recent studies have provided new insight
      into the upstream and downstream components of the MAPK pathway that facilitate
      the activation and propagation of MAPK signaling in immune responses. Moreover,
      MAPK activity is negatively regulated by MAPK phosphatases (MKPs), a group of
      dual-specificity phosphatases that dephosphorylate and inactivate the MAPKs. Here
      we discuss the recent advances in our understanding of these regulatory processes
      in MAPK signaling with a focus on their impacts on immune function.

PMID- 19740677
TI  - Feedback suppression in anesthesia. Is it reversible?
AB  - Information processing that subserves conscious cognitive functions is thought to
      involve recurrent signaling through feedforward and feedback loops among
      hierarchically arranged functional regions of the cerebral cortex. In the current
      issue of Consciousness and Cognition, Lee et al. report that loss of
      consciousness, as produced by a bolus injection of the general anesthetic
      propofol to human volunteers, was accompanied by a decrease in wide-band EEG
      feedback connectivity from frontal cortex to parietal cortex, confirming a
      prediction from previous experimental studies. Interestingly, frontoparietal
      feedback connectivity did not fully recover after the anesthetic effect wore off
      and the subjects first opened their eyes in response to a verbal command.
      Possible interpretations of the results and their implications with respect to
      the neural correlates of consciousness and unconsciousness are discussed.

PMID- 19740678
TI  - Cardiac involvement in Wegener granulomatosis diagnosed at autopsy.
AB  - Wegener granulomatosis (WG) is a systemic vasculitis classically involving the
      lungs, kidneys, and upper respiratory tract. Involvement of other sites does
      occur but is less frequent. Clinically evident cardiac involvement is uncommon.
      There are only a few cases in the literature with documentation of the histologic
      appearance of cardiac involvement in WG. We report a case of a previously healthy
      37-year-old man who presented with a one-week history of cough and weakness and a
      one-day history of shortness of breath. At presentation, he was hypoxic and
      required intubation. Upon hospitalization, he deteriorated rapidly, became
      bradycardic and expired the same night. Infection was suspected clinically as the
      cause of illness and death. At autopsy, the lungs showed diffuse alveolar
      hemorrhage with capillaritis, diffuse alveolar damage, and parenchymal necrosis
      with necrotizing granulomas. The heart was enlarged and showed a mixed
      inflammatory infiltrate composed of neutrophils, eosinophils, and histiocytes,
      with focal myocyte necrosis. Granulomas, giant cells, and vasculitis were absent.
      The esophagus showed submucosal vasculitis. A diagnosis of WG was made.
      Postmortem serology for c-ANCA was positive, and all cultures were negative,
      confirming the diagnosis. Cardiac involvement is an underrecognized and
      potentially fatal complication of WG. The histologic findings in the heart may
      consist of a non-specific inflammatory infiltrate without granulomas or
      vasculitis, raising a wide differential diagnosis.

PMID- 19740679
TI  - Cardiac disease and risk of sudden death in the young: the burden of the
      phenomenon.
AB  - Sudden cardiovascular death is a rare but catastrophic event in young men and
      women throughout the world. Sudden death is difficult to study. Factors that need
      elucidation are (1) the definition of sudden death; (2) diagnosis of the cause of
      sudden death; (3) the true incidence of sudden death, and (4) age and gender of
      individuals being studied. The "burden" of sudden death is far-reaching and
      involves medical, emotional, and economic burdens on the family members at risk,
      the entire family of the victim, and society in general. The pathologist trying
      to evaluate a case of sudden death also has a burden to make the correct
      diagnosis, especially since the cause of the sudden death may determine risk to
      the victim's family members. Sudden death is difficult to prevent since it may be
      the first and last manifestation of the cardiovascular disease. Also,
      paradoxically, the greatest number of deaths occurs in "low-risk" groups. The
      most common causes of cardiovascular deaths in the young are cardiomyopathy,
      coronary anomaly, obstructive coronary artery disease, myocarditis, valvular
      disease, channelopathy, and aortic disease leading to dissection or rupture. Many
      sudden deaths in the young occur during or shortly after exercise. Appropriate
      pre-participation screening of competitive athletes can reduce the incidence of
      sudden cardiovascular death in the young. Which measures to try to prevent these
      rare deaths are indicated and/or cost effective is a matter of discussion and
      controversy.

PMID- 19740680
TI  - Recurrent cardiac amyloidosis following previous heart transplantation.
AB  - Recurrent cardiac amyloidosis has been reported in the literature. We present two
      cases, one at 41 months after heart transplant and autologous stem cell
      transplant, and the other, at 83 months following heart transplantation. The
      former is the first case ever reported of a patient with amyloid light chain
      amyloidosis with systemic recurrence following these two treatment modalities,
      and the latter is a patient with hereditary amyloidosis, whose interval to
      disease recurrence is the longest ever reported for this type.

PMID- 19740681
TI  - Ulnar artery pseudoaneurysm after tension band wiring of an olecranon fracture
      resulting in Volkmann's ischemic contracture: a case report.

PMID- 19740682
TI  - Fibrous dysplasia around the elbow.

PMID- 19740683
TI  - Isolated tuberculous biceps tenosynovitis bicipitoradial bursitis: a case report.

PMID- 19740685
TI  - The complementary value of sleep-deprived EEG in childhood onset epilepsy.
AB  - BACKGROUND: Although EEG is an important diagnostic tool in suspected childhood
      onset epilepsy, as many as 50% of wakefulness records remain normal. Sleep
      deprived EEG has been reported in adults to serve as an activator of epileptic
      discharges but such effect is still not agreed upon in children reporting small
      series. PURPOSE: Assess the complementary diagnostic value of sleep deprivation
      on the induction of epileptic discharges in childhood onset epilepsy having a
      normal awake record within a period of 5 years. EEG recording was performed
      during the awake, drowsiness and sleep states following sleep deprivation of 6h.
      BACKGROUND RESULTS: Fifty five children of whom the initial record failed to
      detect epileptiform discharges, were assessed at age 5-17 years (mean: 10+/-3.7),
      27 boys and 28 girls. Sleep occurred in 51 (92.7%) after sleep deprivation and in
      only 1 (1.8%) during an awake record. Epileptic discharges were detected in 15 of
      55 (27.2%) previous non-epileptic awake records during the sleep-deprived EEG
      either during wakefulness and more frequent during sleep. Eight abnormal records
      were detected in 18 (44%) children presenting with a focal seizure and 7 of 35
      (20%) associated with generalized seizures. Epileptic discharges were recorded
      mainly and more frequent during sleep. CONCLUSIONS: Our data suggests that sleep
      deprivation imposes an apparent activating impact uncovering epileptic discharges
      children corroborating with overt clinical seizures even beyond the sampling
      effect of repeat records.

PMID- 19740684
TI  - Patients' expectations before and satisfaction after ultrasound guided foam
      sclerotherapy for varicose veins.
AB  - OBJECTIVES: Ultrasound guided foam sclerotherapy (UGFS) is a minimally invasive
      treatment for varicose veins (VV) whose clinical and cost-effectiveness remains
      incompletely defined. The aim of the current study was to examine patients'
      expectations before and satisfaction after UGFS for VV in terms of relief of
      lower limb symptoms, improvement in appearance, and beneficial effect on life
      style. METHODS: A consecutive series of 351 patients (464 limbs) undergoing UGFS
      for VV completed questionnaires one week prior to and six months after treatment.
      RESULTS: Pre and post-treatment response rates were 80%; 60% returned both
      questionnaires. Virtually all patients were expecting improvement in lower limb
      symptoms; these were exceeded in a third. Most patients expected cosmetic
      improvement and these were largely met. Two-thirds of patients expected
      significant life-style (clothes, work, social) benefits and outcomes were
      slightly less than expected. A quarter expected improvement in their
      interpersonal relationships. This benefit was greater than expected occurring in
      one-third of patients. Overall, a quarter of patients had their expectations
      exceeded and 10% (appearance and relationships) to 25% (clothing, work and social
      and leisure activities) were left with unmet expectations. DISCUSSION: When
      specifically asked most patients admit to having a wide range of expectations in
      relation to their VV treatment, many of them probably unanticipated by the
      clinician. However, present data indicate that UGFS is usually able to meet, and
      often exceeds, these physical and psychosocial needs and expectations. UGFS is,
      therefore, a highly effective treatment for VV from the patients' perspective.

PMID- 19740686
TI  - Quantitative single point imaging with compressed sensing.
AB  - A novel approach with respect to single point imaging (SPI), compressed sensing,
      is presented here that is shown to significantly reduce the loss of accuracy of
      reconstructed images from under-sampled acquisition data. SPI complements
      compressed sensing extremely well as it allows unconstrained selection of
      sampling trajectories. Dynamic processes featuring short T2* NMR signal can thus
      be more rapidly imaged, in our case the absorption of moisture by a cereal-based
      wafer material, with minimal loss of image quantification. The absolute moisture
      content distribution is recovered via a series of images acquired with variable
      phase encoding times allowing extrapolation to time zero for each image pixel and
      the effective removal of T2* contrast.

PMID- 19740687
TI  - Structural features and dynamics properties of human apolipoprotein A-I in a
      model of synthetic HDL.
AB  - High-density lipoproteins (HDL) play a major role in the reverse transport of
      cholesterol and have antiatherogenic activities. Their major protein component is
      apolipoprotein (apo) A-I. While apoA-I amphipathic alpha-helix based secondary
      structure has been extensively investigated, for its lipid-bound tertiary
      structure only theoretical models have been proposed. In the past years,
      experimental approaches aimed at a direct visualization of HDL structure have
      been exploited, but data obtained through different microscopy techniques are
      conflicting and do not settle the issue. Here we present a 50 ns molecular
      dynamics simulation of a synthetic HDL containing two molecules of apoA-I and 101
      of l-alpha-palmitoyl-oleoyl-phosphatidylcholine. Essential dynamics and
      structural property investigations suggest that the stabilization of the system
      is obtained through specific motions, whose driving forces are protein
      phospholipid interactions. The most important are: the relative sliding of the
      two apoA-I molecules along their major axes, the relative rotation of the protein
      chains, and the out-of-plane deformation around proline hinges. The sliding and
      the out-of-plane deformation allow apoA-I to optimize its interactions with
      phospholipids, while the rotation is useful to maximize protein-protein salt
      bridges. The correspondence between computed parameters and their experimental
      counterparts contributes to validate our model and its dynamic behaviors. Our
      findings help in defining a molecular model for apoA-I contained in HDL and
      suggest a possible mechanism through which apoA-I can vary its diameter and
      accommodate different numbers of phospholipids during the metabolism of HDL.

PMID- 19740688
TI  - Successful surgical treatment of a prostatic biphasic tumour (sarcomatoid
      carcinoma) in a cat.
AB  - A 12-year-old, neutered male, mixed-breed, domestic cat was presented for dysuria
      and haematuria accompanied by recurrent dyschezia and constipation. At rectal
      digital examination a non-painful, globose and relatively immobile mass was
      detected at the pelvic brim, ventral to the rectum. Abdominal ultrasound showed
      the prostate replaced by a mass with a regular shape but patchy/non-uniform
      echogenicity. A prostatectomy followed by prepubic urethrostomy was performed. At
      histopathology the tumour was composed of epithelial ducts and acini with
      malignant features, surrounded by proliferating cellular stroma with mitoses and
      nuclear atypia; an immunohistochemical panel confirmed the biphasic nature of the
      tumour proliferation. The diagnosis was non-infiltrating malignant mixed tumour,
      resembling human sarcomatoid carcinoma of the prostate. Two years after surgery
      the animal has not shown any health problems. To the author's knowledge, this is
      the first reported case of prostatic tumour with a positive follow-up after
      surgical treatment in cat.

PMID- 19740689
TI  - Prospective evaluation of tissue plasminogen activator in 11 cats with arterial
      thromboembolism.
AB  - The purpose of this study was to evaluate the clinical response and side effects
      of tissue plasminogen activator (tPA) for the treatment of feline arterial
      thromboembolism (ATE). Previous reports of conservative and thrombolytic therapy
      were used to provide a historical control group of cats with ATE. The study was
      terminated due to a high frequency of adverse outcomes. tPA was administered to
      11 cats with clinical signs of ATE for a median duration of 4.0 h (range 2-12h)
      prior to treatment. Pulses were restored in 40% of limbs within 4h and 53% within
      24h. Motor function was restored to 33% of limbs within 24h. Adverse effects were
      seen in 11/11 cats following administration of tPA including azotemia (n=5),
      neurological signs (n=5), cardiac arrhythmias (n=5), hyperkalemia (n=4), acidosis
      (n=2) and sudden death in one cat. Ultimately, three cats (27%) were discharged
      alive from the hospital. While signs compatible with thrombolysis were noted in
      many cats following tPA administration, a high rate of side effects and low rate
      of hospital discharge were noted in this study.

PMID- 19740690
TI  - [Descriptive study of the type of patient cared for in a link-nursing program].
AB  - OBJECTIVE: Determine the type of patients in a program of link nursing of the
      urban area. METHODS: Descriptive observational study conducted at the Hospital
      Clinic de Barcelona (HCB). The study population were patients hospitalized in the
      Institute of Orthopedics, Internal Medicine, Cardiology, Vascular Surgery and
      Post Coronary Care. The data was obtained through the registration of patients
      enrolled in the program between November 2006 and April 2008. We analyzed
      sociodemographic variables (gender, age, reason for admission, the institution
      where hospitalized, hospital stay, primary care (PAC) reference destination of
      the patient on discharge from hospital) and physical variables (Barthel
      dependency score and recommendations of the link nurse to reference PAC).
      RESULTS: Information was analysed from 2025 (99.26%) out of 2040 eligible
      patients. Fifteen were excluded because they did not have complete information
      for data analysis. The average age for men was 73.55 years and 66.53 years for
      women (P<0.01). There was sever dependence in 92 (9.10%) males and 61 (6.02%)
      women (P<0.01). The average number of hospital stays for men was 9.7 and 9.65 for
      women (P<0.01). Continuity of care at home was not required in 571 (56.48%) males
      and 605 (59.66%). CONCLUSIONS: The majority of the population was elderly with an
      index of slight dependence, demonstrating that this population need continuous
      monitoring of their progress after discharge, although the Barthel index was not
      severe or total.

PMID- 19740691
TI  - Allele frequency distribution for 15 autosomal STR loci in Afridi Pathan
      population of Uttar Pradesh, India.
AB  - Allele frequencies of the 15 autosomal short tandem repeat (STR) loci D8S1179,
      D21S11, D7S820, CSF1PO D19S433, vWA, TPOX, D18S51, D3S1358, THO1, D13S317,
      D16S539, D2S1338, D5S818 and FGA were determined in Afridi Pathan population of
      Uttar Pradesh, India. All the 15 STR loci studied were found to be highly
      polymorphic with respect to observed heterozygosity values. Adherence to the
      expectations of the Hardy-Weinberg equilibrium (HWE) was confirmed for all the
      loci with an exception of TPOX and FGA. The allele 12 in CSF1PO was found to be
      most frequent. The power of discrimination was found to be high ranging from a
      minimum of 0.858 for the locus CSFIPO to maximum of 0.962 for the locus FGA,
      thereby facilitating the validation and efficiency of these STR markers in human
      identification. Population differentiation test between the studied and
      neighboring populations revealed significant differences at several loci
      suggesting the endogamous nature of the studied population. To the best of our
      knowledge, Afridi Pathan population has not been explored genetically for
      generating forensic data on STR markers. Therefore, STR allele frequency data of
      this unique population is a valuable contribution to the existing DNA database on
      Indian populations.

PMID- 19740692
TI  - Population genetic data for 15 STR loci (Identifiler kit) in Bolivia.
AB  - Allele frequencies for 15 STR autosomal loci (D8S1179, D21S11, D7S820, CSF1PO,
      D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, VWA, TPOX, D18S51, D5S818 and
      FGA) were obtained from a sample of 200 unrelated individuals from Bolivia, South
      America.

PMID- 19740693
TI  - Population genetic data on 15 autosomal STRs in a Pakistani population sample.
AB  - Allele frequencies for the 15 STR loci (D3S1358, TH01, D21S11, D18S51, Penta E,
      D5S818, D13S317, D7S820, D16S539, CSF1PO, Penta D, VWA, D8S1179, TPOX and FGA)
      were investigated using PowerPlex((R))16 amplification kit in a sample of 328
      unrelated individuals from Islamic Republic of Pakistan. The allelic
      distributions were in Hardy Weinberg equilibrium for all loci except for the loci
      FGA, TPX and THO1. Various forensic indices were calculated and a comparison was
      made with geographically nearby populations.

PMID- 19740694
TI  - Ultrasound promoted synthesis of thioesters from 2-mercaptobenzoxa(thia)zoles.
AB  - An ultrasound-enhanced method has been developed for the synthesis of a variety
      of thioesters from benzoyl chlorides and 2-mercaptobenzoxa(thia)zoles. Applying
      this methodology, 14 compounds were synthesized in excellent yields.

PMID- 19740695
TI  - Modeling the relationship between wrist angle and muscle thickness during wrist
      flexion-extension based on the bone-muscle lever system: a comparison study.
AB  - A structural model of skeletal muscle based on the bone-muscle lever system is
      proposed to describe the relationship between wrist angle and thickness of the
      extensor carpi radialis muscle during the process of wrist flexion-extension.
      This model applied the cosine theorem to the expression for muscle length, in
      order to relate wrist angle to muscle thickness by the invariance of muscle
      volume, which was used to calculate the length of the extensor carpi radialis
      muscle from the muscle thickness. To validate the proposed model, wrist angles
      were also computed by other models based on regression, such as linear
      regressions, an artificial neural network, and a support vector machine. The
      results show that wrist angles are predicted well at different extension rates by
      our proposed model, with correlation coefficient (R(2)) greater than 0.94,
      standard root mean square error (SRMSE) less than 8.0 and relative root mean
      square error (RRMSE) less than 13%. These parameters show that the proposed model
      is better than the other regression-based models (p<0.05). More importantly, this
      model can be clearly related to physiology. Thus, it can potentially be used to
      investigate the relationship between internal structural changes of skeletal
      muscle and external limb behaviors, and to develop prosthetic hands and
      functional electrical stimulation systems.

PMID- 19740696
TI  - Identifying druggable disease-modifying gene products.
AB  - Many disease genes encode proteins that are difficult to target directly using
      small molecule drugs. Improvements in libraries based on synthetic compounds,
      natural products, and other types of molecules may ultimately allow some
      challenging proteins to be successfully targeted; however, these developments
      alone are unlikely to be sufficient. A complementary strategy exploits the
      functional interconnectivity of intracellular networks to find druggable targets
      lying upstream, downstream, or in parallel to a disease-causing gene, where
      modulation can influence the disease process indirectly. These targets can be
      selected using prior knowledge of disease-associated pathways or identified using
      phenotypic chemical and genetic screens in model organisms and cells. These
      approaches should facilitate the identification of effective drug targets for
      many genetic disorders.

PMID- 19740697
TI  - From single molecules to whole organisms: the evolving field of mechanistic
      enzymology.

PMID- 19740698
TI  - Cytokinin action in plant development.
AB  - Cytokinin regulates many important aspects of plant development in aerial and
      subterranean organs. The hormone is part of an intrinsic genetic network
      controlling organ development and growth in these two distinct environments that
      plants have to cope with. Cytokinin also mediates the responses to variable
      extrinsic factors, such as light conditions in the shoot and availability of
      nutrients and water in the root, and has a role in the response to biotic and
      abiotic stress. Together, these activities contribute to the fine-tuning of
      quantitative growth regulation in plants. We review recent progress in
      understanding the cytokinin system and its links to the regulatory pathways that
      respond to internal and external signals.

PMID- 19740699
TI  - Synthesis, structure and spectroscopic properties of two new trinuclear
      nickel(II) clusters possessing solvent effect.
AB  - Two solvent-induced trinuclear nickel(II) clusters,
      [{NiL(CH(3)OH)}(2)(OAc)(2)Ni].2CH(3)OH (I) and
      [{NiL(C(2)H(5)OH)}(2)(OAc)(2)Ni].2C(2)H(5)OH (II), have been synthesized by the
      reaction of a new Salen-type bisoxime chelating ligand of 5,5'-di(N,N'
      diethylamino)-2,2'-[(1,3-propylene)dioxybis(nitrilomethylidyne)]diphenol (H(2)L)
      with nickel(II) acetate tetrahydrate in different solvents. Clusters I and II
      were characterized by elemental analyses, IR spectra, UV-vis absorption spectra,
      TG-DTA and X-ray diffraction methods. In clusters I (or II), there are two ligand
      moieties (which provide N(2)O(2) donors), two acetate ions, two coordinated
      methanol (or ethanol) molecules and two crystallizing methanol (or ethanol)
      molecules, which result in the formation of three slightly distorted octahedral
      geometries around Ni(II) ions. Interestingly, nickel(II) ions in the structures
      of clusters I and II are all six-coordinated geometry, but clusters I and II are
      grown up in different solvent. Right because of this, solvent effect cause to
      their different crystal structures.

PMID- 19740700
TI  - Example of a Human Factors Engineering approach to a medication administration
      work system: potential impact on patient safety.
AB  - OBJECTIVE: The objectives of this paper are: In this approach, the implementation
      of such a complex IT solution is considered a major redesign of the work system.
      The paper describes the Human Factor (HF) tasks embedded in the project
      lifecycle: (1) analysis and modelling of the current work system and usability
      assessment of the medication CPOE solution; (2) HF recommendations for work re
      design and usability recommendations for IT system re-engineering both aiming at
      a safer and more efficient work situation. METHODS: Standard ethnographic methods
      were used to support the analysis of the current work system and work situations,
      coupled with cognitive task analysis methods and documents review. Usability
      inspection (heuristic evaluation) and both in-lab (simulated tasks) and on-site
      (real tasks) usability tests were performed for the evaluation of the CPOE
      candidate. Adapted software engineering models were used in combination with
      usual textual descriptions, tasks models and mock-ups to support the
      recommendations for work and product re-design. RESULTS: The analysis of the work
      situations identified different work organisations and procedures across the
      hospital's departments. The most important differences concerned the doctor-nurse
      communications and cooperation modes and the procedures for preparing and
      administering the medications. The assessment of the medication CPOE functions
      uncovered a number of usability problems including severe ones leading to
      impossible to detect or to catch errors. Models of the actual and possible
      distribution of tasks and roles were used to support decision making in the work
      design process. The results of the usability assessment were translated into
      requirements to support the necessary re-engineering of the IT application.
      CONCLUSION: The HFE approach to medication CPOE efficiently identifies and
      distinguishes currently unsafe or uncomfortable work situations that could
      obviously benefit from an IT solution from other work situations incorporating
      efficient work procedures that might be impaired by the implementation of the
      CPOE. In this context, a careful redesign of the work situation and of the entire
      work system is necessary to actually benefit from the installation of the product
      in terms of patient safety and human performances. In parallel, a usability
      assessment of the product to be implemented is mandatory to identify potentially
      dangerous usability flaws and to fix them before the installation.

PMID- 19740701
TI  - Mechanisms of bone repair and regeneration.
AB  - Bone problems can have a highly deleterious impact on life and society, therefore
      understanding the mechanisms of bone repair is important. In vivo studies show
      that bone repair processes in adults resemble normal development of the skeleton
      during embryogenesis, which can thus be used as a model. In addition, recent
      studies of skeletal stem cell biology have underlined several crucial molecular
      and cellular processes in bone formation. Hedgehog, parathyroid hormone-related
      protein, Wnt, bone morphogenetic proteins and mitogen-activated protein kinases
      are the main molecular players, and osteoclasts and mesenchymal stem cells are
      the main cells involved in these processes. However, questions remain regarding
      the precise mechanisms of bone formation, how the different molecular processes
      interact, and the real identity of regenerative cells. Here, we review recent
      studies of bone regeneration and repair. A better understanding of the underlying
      mechanisms is expected to facilitate the development of new strategies for
      improving bone repair.

PMID- 19740702
TI  - Is there a learning curve for subureteric injection of dextranomer/hyaluronic
      acid in the treatment of vesicoureteral reflux?
AB  - OBJECTIVE: To answer the question: 'Is there a learning curve associated with a
      subureteric injection of Deflux((r))?' MATERIALS AND METHODS: We retrospectively
      reviewed charts of patients who received subureteric injection of
      dextranomer/hyaluronic acid (Deflux((r)){AQ2}) (225 procedures) for treatment of
      vesicoureteral reflux (VUR) by four surgeons. The study included 55 patients, 82
      ureters, who had postoperative follow-up with a voiding cystogram or nuclear
      medicine cystogram. Exclusion criteria were prior anti-refluxing procedures,
      duplicated collecting systems, and non-achievement of a negative intraoperative
      cystogram. Patients were divided into two groups based on whether or not they
      received an intraoperative cystogram after the injection. The two groups were
      compared for VUR resolution rates on follow-up imaging. RESULTS: Twenty patients
      underwent an intraoperative cystogram (Group 1, 33 ureters) and 35 did not (Group
      2, 49 ureters). The two groups were similar in age, preoperative reflux grade,
      amount of Deflux injected into each ureter, and time to postoperative studies. In
      Group 1, 11 ureters (33.3%) and also, in Group 2, 11 ureters (22.4%) had reflux
      on follow-up imaging. CONCLUSIONS: There was no improvement in VUR resolution
      rate following subureteric injection of Deflux((r)) when an intraoperative
      cystogram demonstrated no reflux to be present immediately after injection. Of
      ureters that did not reflux on intraoperative cystograms, one-third displayed
      return of reflux on follow-up imaging, which suggests no learning curve and that
      failures are not likely to be caused by poor surgical technique.

PMID- 19740703
TI  - Reversible severe combined immunodeficiency phenotype secondary to a mutation of
      the proton-coupled folate transporter.
AB  - Hereditary folate malabsorption is a rare inborn error of metabolism due to
      mutations in the proton-coupled folate transporter (PCFT). Clinical presentation
      of PCFT deficiency may mimic severe combined immune deficiency (SCID). We report
      a 4-month-old female who presented with failure to thrive, normocytic anemia,
      Pneumocystis jirovecii pneumonia and systemic cytomegalovirus infection.
      Immunological evaluation revealed hypogammaglobulinemia, absent antibody
      responses, and lack of mitogen-induced lymphocyte proliferative responses.
      However, the absolute number and distribution of lymphocyte subsets, including
      naive T cells and recent thymic emigrants, were normal, arguing against primary
      SCID. Serum and cerebrospinal fluid folate levels were undetectable. A homozygous
      1082-1G>A mutation of the PCFT gene was found, resulting in skipping of exon 3.
      Parenteral folinic acid repletion resulted in normalization of anemia, humoral
      and cellular immunity, and full clinical recovery. PCFT mutations should be
      considered in infants with SCID-like phenotype, as the immunodeficiency is
      reversible with parenteral folinic acid repletion.

PMID- 19740704
TI  - Differential susceptibility to apoptosis of CD4+T cells expressing CCR5 and CXCR3
      in patients with MS.
AB  - We aimed to evaluate differences in the susceptibility to apoptosis of CD4+CCR5+
      and CD4+CXCR3+T cells between MS patients (N=41) and controls (N=15) 6 days after
      activation of peripheral blood cells with anti-CD3 antibodies and 24 h following
      stimulation with anti-Fas antibodies. Susceptibility to anti-CD3 induced
      activation-induced cell death (AICD) and Fas-mediated apoptosis was selectively
      increased in CD4+CCR5+T cells compared with CD4+CCR5- and CD4+CXCR3-/+T cells.
      Compared with controls, CD4+CCR5+T cells from patients with primary progressive
      MS (PPMS) were more resistant to anti-CD3-induced AICD and anti-Fas-induced
      apoptosis determined with the mitochondrial probe DiOC(6) (3-3'
      dihexyloxacarboyanine iodide). Our findings point to a differential regulation in
      the susceptibility to apoptosis of CD4+T cells expressing CCR5 and CXCR3 and
      suggest an impairment in the mitochondria-mediated apoptotic deletion of
      CD4+CCR5+T cells in PPMS patients that may lead to their chronic persistence in
      peripheral blood from these patients.

PMID- 19740705
TI  - The role of resistin as a regulator of inflammation: Implications for various
      human pathologies.
AB  - Resistin was originally described as an adipocyte-secreted peptide that induced
      insulin resistance in rodents. Increasing evidence indicates its important
      regulatory roles in various biological processes, including several inflammatory
      diseases. Further studies have shown that resistin in humans, in contrast to its
      production by adipocytes in mice, is synthesized predominantly by mononuclear
      cells both within and outside adipose tissue. Possible roles for resistin in
      obesity-related subclinical inflammation, atherosclerosis and cardiovascular
      disease, non-alcoholic fatty liver disease, rheumatic diseases, malignant tumors,
      asthma, inflammatory bowel disease, and chronic kidney disease have already been
      demonstrated. In addition, resistin can modulate several molecular pathways
      involved in metabolic, inflammatory, and autoimmune diseases. In this review,
      current knowledge about the functions and pathophysiological implications of
      resistin in different human pathologies is summarized, although there is a
      significant lack of firm evidence regarding the specific role resistin plays in
      the "orchestra" of the numerous mediators of inflammation.

PMID- 19740706
TI  - Innate immune signals in atherosclerosis.
AB  - Atherosclerosis is a chronic disease characterised by lipid retention and
      inflammation in the arterial intima. Innate immune mechanisms are central to
      atherogenesis, involving activation of pattern-recognition receptors (PRRs) and
      induction of inflammatory processes. In a complex tissue, such as the
      atherosclerotic lesion, innate signals can originate from several sources and
      promote atherogenesis through ligation of PRRs. The receptors recognise conserved
      molecular patterns on pathogens and endogenous products of tissue injury and
      inflammation. Activation of PRRs might affect several aspects of atherosclerosis
      by acting on lesion resident cells. Scavenger receptors mediate antigen uptake
      and clearance of lipoproteins, thereby promoting foam cell formation. Signalling
      receptors, such as Toll-like receptors (TLRs), lead to induction of pro
      inflammatory cytokines and antigen-specific immune responses. In this review we
      describe the innate mechanisms present in the plaque. We focus on TLRs, their
      cross-talk with other PRRs, and how their signalling cascades influence
      inflammation within the atherosclerotic lesion.

PMID- 19740707
TI  - AA28-67 domain within MyD88 suppresses c-myc activity and expression to regulate
      differentiation and function of dendritic cells.
AB  - The mechanism by which c-myc expression in undifferentiated cells rapidly
      declines following induction of differentiation is poorly characterized. We
      demonstrate here that MyD88, which can activate NF-kappaB and MAPK, also
      suppresses c-myc activity and expression. The aa 28-67 domain, a highly conserved
      region within MyD88, plays a critical role in the MyD88-mediated inhibition.
      Indeed, deletion of the aa 28-67 domain (MyD88 Delta 28-67) or mutation of the
      highly conserved amino acid residue phenylalanine (aa 36) to aspartic acid (MyD88
      Delta F36D) significantly promoted c-myc activity and expression. Additionally,
      we found that MyD88 Delta 28-67-mediated c-myc activity and expression could be
      abrogated using PI3K inhibitor, suggesting that the PI3K/Akt signaling pathway
      may be involved in MyD88-mediated suppression of c-myc. Compared to MyD88
      transduced DCs, MyD88 Delta 28-67- and MyD88 Delta F36D-transduced DCs derived
      from MyD88-/- bone marrow cells had lower antigen-presenting ability. Thus, MyD88
      induces the differentiation and maturation of DCs not only by activating NF
      kappaB and MAPK but also via suppressing c-myc activity and expression.

PMID- 19740709
TI  - Gynaecologic cancer complicating pregnancy: an overview.
AB  - Cancer complicating pregnancy endangers two lives. Any approach should look at
      both maternal and foetal safety. Maternal prognosis will not improve by
      terminating the pregnancy. Imaging for staging purposes is possible, and sonar
      and magnetic resonance imaging are the preferred examinations. Abdominopelvic
      computed tomography exposes the foetus to the highest doses radiation and should
      be avoided. Provided a thorough maternal monitoring to ensure a stable
      uteroplacental blood flow and foetal oxygenation, surgical techniques that are
      used in non-pregnant patients are also safe for pregnant patients. Radiotherapy
      of the upper part of the body is possible during pregnancy, but during the third
      trimester the close distance may put the foetus at risk. Chemotherapy during the
      second or third trimester can be administered without increasing the incidence of
      congenital malformations. A systematic analysis, especially on the long-term
      outcome of the offspring after cancer treatment during pregnancy is still
      lacking. Here, we present a summary of issues related to the diagnosis and
      treatment of gynaecological malignancies during pregnancy. Firstly, we describe
      general diagnostic and cancer-treatment-related problems. In the second part,
      organ pathology including breast, cervical, ovarian, endometrial and vulvar
      cancer is discussed.

PMID- 19740710
TI  - Trends in pathogens colonising the respiratory tract of adult patients with
      cystic fibrosis, 1985-2005.
AB  - INTRODUCTION: The treatment of patients with CF has continued to evolve. We
      hypothesised that sputum microbiology may have changed as a result of this.
      METHOD: Retrospective analysis of sputum microbiology from adult CF patients
      (1985 to 2005) using the Royal Brompton Hospital CF database. RESULTS:
      Colonisation with Pseudomonas aeruginosa or Staphylococcus aureus between 1985
      and 2005 remained stable (77 to 82%, p=0.159; 54 to 47%, p=0.108; respectively).
      Haemophilus influenzae (48 to 6%; p<0.001), Aspergillus species (18 to 9%;
      p=0.002) and Burkholderia cepacia complex (9 to 4%; p=0.041) prevalence
      decreased. Stenotrophomonas maltophilia and MRSA increased (1 to 4%, p=0.02; 1 to
      6%, p=0.002, respectively). CONCLUSION: P. aeruginosa colonisation has remained
      stable; there has been a decline in B. cepacia complex, H. influenzae and
      Aspergillus sp., and only a small increase in S. maltophilia and MRSA. Intensive
      antibiotic strategies have been employed, which, so far, have not resulted in
      clinically significant emergence of new pathogens.

PMID- 19740711
TI  - A safe protocol for rapid desensitization in patients with cystic fibrosis and
      antibiotic hypersensitivity.
AB  - BACKGROUND: CF patients often demonstrate hypersensitivity to one or multiple
      antibiotics due to frequent and repeated exposures. Attempts at antibiotic
      desensitization in this population are historically complicated by higher
      reaction rates, failure to complete the procedure and consequent withholding of
      first-line therapy. This study evaluates the outcomes of a rapid desensitization
      protocol developed at our institution. METHODS: We retrospectively reviewed the
      medical records of 15 patients undergoing 52 rapid antibiotic desensitizations at
      Brigham and Women's Hospital and Children's Hospital Boston utilizing our
      protocol. RESULTS: Mean FEV1 % predicted was 44.1 (SD 16.5), with two patients at
      <30% and one patient desensitized during bilateral lung transplantation. Adverse
      reactions during desensitization occurred in 13.4%, and most were mild. 100% of
      patients completed the protocol and ultimately tolerated subsequent full-strength
      antibiotic courses. CONCLUSIONS: CF patients with antibiotic hypersensitivity can
      safely receive first-line antibiotics via our rapid desensitization protocol,
      including those with severe obstructive lung disease.

PMID- 19740712
TI  - Simultaneous quantification of 9-(beta-D-1,3-dioxolan-4-yl)guanine, Amdoxovir and
      Zidovudine in human plasma by liquid chromatography-tandem mass spectrometric
      assay.
AB  - A sensitive method was developed and validated for simultaneous measurement of an
      investigational antiviral nucleoside, Amdoxovir (DAPD), its deaminated metabolite
      9-(beta-D-1,3-dioxolan-4-yl)guanine (DXG), and Zidovudine (ZDV) in human plasma.
      This method employed high-performance liquid chromatography-tandem mass
      spectrometry with electrospray ionization. DXG and DAPD separation with
      sufficient resolution was necessary since they differ in only one mass to charge
      ratio, which increases the risk of overlapping MS/MS signals. However, the new
      method was observed to have functional sensitivity and specificity without
      interference. Samples were purified by ultrafiltration after protein
      precipitation with methanol. The total run time was 29 min. A linear calibration
      range from 2 to 3000 ng mL(-1) and 2 to 5000 ng mL(-1) was achieved for DAPD and
      DXG, and ZDV, respectively. Precisions and accuracies were both +/-15% (+/-20%
      for the lower limit of quantification) and recoveries were higher than 90%.
      Matrix effects/ion suppressions were also investigated. The analytes were
      chemically stable under all relevant conditions and the method was successfully
      applied for the analysis of plasma samples from HIV-infected persons treated with
      combinations of DAPD and ZDV.

PMID- 19740713
TI  - The putative role of the intestinal microbiota in the irritable bowel syndrome.
AB  - The irritable bowel syndrome (IBS) is a chronic abdominal symptom complex that is
      heterogeneous in terms of its clinical presentation and underlying
      pathophysiology and pathogenesis. It is now established that enteric infection
      can trigger the syndrome in at least a subset of patients. In addition, there is
      growing evidence of low grade inflammation and immune activation in the distal
      bowel of some IBS patients. These observations now prompt the question as to what
      maintains gut dysfunction in these patients. The intestinal microbiota influences
      a broad array of host organs that include the gut and the brain, and is an
      important determinant of normal function in these systems. Disruption of the
      delicate balance between the host and its intestinal microbiota (termed
      dysbiosis) results in changes in the mucosal immune system that range from overt
      inflammation as seen in Crohn's Disease, to low grade inflammation without tissue
      injury, as seen in a subset of IBS patients. Under experimental conditions,
      disruption of the microbiota also produces changes in gut sensory-motor function
      and immune activity. Thus, dysbiosis induced by infection, dietary change or
      drugs such as antibiotics could produce low grade inflammation and chronic gut
      dysfunction, reminiscent of that seen in IBS. Fluctuations in gut physiology
      destabilize the habitat of commensal bacteria and provide a basis for chronic
      dysbiosis. Recent observations in animal models that changes in gut flora
      influence behavior provide a basis for a novel unifying hypothesis that
      accommodates both gut dysfunction and behavioral changes that characterize many
      IBS patients. This hypothesis states that dysbiosis exists in at least a subset
      of IBS patients, as a result of infection, dietary change or drugs and
      contributes to gut inflammatory and functional change in addition to psychiatric
      co-morbidity.

PMID- 19740714
TI  - Arthroscopic removal of an osteoid osteoma of the talar neck.
AB  - Osteoid osteoma is uncommonly located at the ankle joint level. Arthroscopic
      resection is an unusual treatment modality in this tumour situation. We report
      the case of a young man presenting with an osteoid osteoma of his talus neck.
      Diagnosis was made by MRI. Since the tumour was intraarticular and subperiosteal,
      it was arthroscopically removed. Pathological examination confirmed the diagnosis
      of osteoid osteoma. Recovery was uneventful; immediate and complete pain relief
      followed surgery and the patient remains asymptomatic several months after his
      operation. Arthroscopic techniques allow complete exploration of the joint and
      total excision of the tumour. This minimally invasive approach reduces infectious
      and functional risks (joint stiffness). Less invasive resection techniques should
      be advocated, when applicable, to achieve pathological diagnosis of the surgical
      specimen.

PMID- 19740715
TI  - Congenital tibial deficiencies: treatment using the Ilizarov's external fixator.
AB  - INTRODUCTION: Congenital longitudinal deficiency of the tibia is a rare and often
      syndromic anomaly. Amputation is usually the preferred treatment option in
      complete absence of the tibia; however, a conservative management might be
      implemented in partial forms or in case of amputation refusal. Our experience
      with the Ilizarov fixator, convinced us this device was the best suited for
      progressive correction of lower limbs length discrepancies and articular or bone
      angular limb deformities (ALD). The aim of this study is to highlight the
      interest of the Ilizarov fixator in the multistage conservative treatment of
      congenital tibial deficiencies. MATERIAL AND METHODS: A retrospective study was
      conducted in nine patients suffering from Type I or II congenital tibial
      deficiencies (Jones) and sequentially managed using the Ilizarov technique. The
      functional outcome after treatment completion was then clinically assessed.
      RESULTS: The different stages of correction were recorded for each individual
      patient. Patients were assessed at a mean follow-up of 18,3 years (4-32 years).
      The mean maximum knee flexion was 35 degrees (0 degrees -90 degrees ) in type I
      deficiencies and 118 degrees (90 degrees -140 degrees ) in type II deficiencies.
      One patient underwent amputation and a bilateral knee arthrodesis was performed
      in another case. DISCUSSION: Few series in the literature report a comparable
      length of follow-up period in the conservative management of severe congenital
      tibial deficiencies. In our study, the Ilizarov fixator provided satisfactory
      progressive corrections of severe congenital tibial deficiencies. LEVEL OF
      EVIDENCE: Level IV therapeutic retrospective study.

PMID- 19740716
TI  - Bilateral simultaneous metal inlay dissociation from the polyethylene liner of a
      metal-on-metal hip replacement.
AB  - INTRODUCTION: Hard-on-hard bearings for total hip replacement may require a
      modular acetabular inlay for which polyethylene is often used in a sandwich-type
      configuration. However, differences in the elastic modulus of the materials make
      fixation of this metal insert uncertain. The aim of this study is to report a
      case of bilateral separation of the metal insert from the polyethylene sandwich
      in a metal-on-metal bearings prosthesis. MATERIALS AND METHODS: A bilateral total
      hip arthroplasty was performed in two operations, four months apart, in a 53-year
      old woman following a corticosteroid-induced osteonecrosis. The total hip
      replacement system included a cementless stem, and a press-fit hemispheric cup
      containing a polyethylene sandwich with a metallic insert (Sikomet). RESULTS:
      Three years later, the patient consulted because of abnormal noise in her right
      hip which appeared normal on conventional X-ray. Three months later she consulted
      again for persistent noise. Separation of the metal insert from the polyethylene
      sandwich was diagnosed and an acetabular revision was performed selecting a metal
      on-polyethylene articulation system. The postoperative course, for this revision,
      was uneventful, but the patient returned with the similar symptoms in her left
      hip four months later, resulting in the same type of revision. During the
      revisions, osteolysis secondary to metallosis was diagnosed, requiring
      synovectomy and acetabular reconstruction with morcelized allograft impaction.
      The left side postoperative course included three dislocations in nine months
      which were conservatively treated and have not since recurred. DISCUSSION AND
      CONCLUSION: This is the first reported case recording an almost simultaneous
      bilateral dissociation of a hard-on-hard inlay from its polyethylene sandwich.
      This bilateral case suggests that the fixation of the metal insert inside the
      polyethylene was probably defective. This case is also a reminder that mechanical
      complications (separation, implant fracture) should be searched for in presence
      of any abnormal noise occurring after hard-on-hard bearings prosthetic
      implantation. This confirms the necessity of periodical follow-up of hip
      arthroplasties and the importance of knowing their radiological features. The low
      carbon content of the Sikomet bearing may have been the cause of this failure by
      increasing frictional torque on the bearing surface, causing metallosis which has
      already been described in the literature in this type of hip replacement system.

PMID- 19740717
TI  - Application of an automatic conversation intelligibility test system using
      computerized speech recognition technique.
AB  - PURPOSE: Subjective speech evaluation is important in maxillofacial
      rehabilitation. In previous research, the automatic speech intelligibility test
      system using monosyllables was developed using a computerized speech recognition
      technique, and it was suggested that the system may effectively be used in
      evaluated maxillectomy patients' speech. However the system showed some
      disadvantages such as the low sensitiveness for the mild speech disorders. In
      this study, the system was remodeled employing sentences as test stimuli to
      overcome the shortcomings. The new system was used to evaluate speech of normal
      adults and maxillectomy patients. METHODS: The speech of 10 normal adults and 13
      maxillectomy patients was evaluated using the automatic conversation
      intelligibility test system that employed sentences as test stimuli. Normal
      subjects repeated the test for three times on different days. The patients'
      utterances were examined in two conditions: with and without prostheses. The
      results from patients with and without prostheses were compared to each other,
      and also compared with their corresponding conversation intelligibility obtained
      using a perceptual method. RESULTS: In normal subjects, there was no significant
      difference in their scores using the automatic conversation intelligibility test
      on three different days. The result of the automatic test was significantly
      improved in patients by wearing prostheses. There were significant correlations
      between the result of the automatic test and the corresponding conversation
      intelligibility both in patients with prostheses and without prostheses.
      CONCLUSION: It was indicated that the automatic conversation intelligibility test
      system using sentences as stimuli would be effectively used in evaluating
      maxillectomy patients' speech.

PMID- 19740718
TI  - Paradoxical ictal EEG lateralization in children with unilateral encephaloclastic
      lesions.
AB  - BACKGROUND: Describe an ictal EEG pattern of paradoxical lateralization in
      children with unilateral encephaloclastic hemispheric lesion acquired early in
      life. METHODS: Of 68 children who underwent hemispherectomy during 2003-2005,
      scalp video-EEG and brain MRI of six children with an ictal scalp EEG pattern
      discordant to the clinical and imaging data were reanalyzed. Medical charts were
      reviewed for clinical findings and seizure outcome. RESULTS: Age of seizure onset
      was 1 day-4 years. The destructive MRI lesion was an ischemic stroke in 2, a post
      infectious encephalomalacia in 2, and a perinatal trauma and hemiconvulsive
      hemiplegic syndrome in one patient each. Ictal EEG pattern was characterized by
      prominent ictal rhythms with either 3-7 Hz spike and wave complexes or beta
      frequency sharp waves (paroxysmal fast) over the unaffected (contralesional)
      hemisphere. Scalp video-EEG was discordant, however, other findings of motor
      deficits (hemiparesis; five severe, one mild), seizure semiology (4/6),
      interictal EEG abnormalities (3/6), and unilateral burden of MRI lesion guided
      the decision for hemispherectomy. After 12-39 months of post-surgery follow up,
      five of six patients were seizure free and one has brief staring spells.
      CONCLUSION: We describe a paradoxical lateralization of the EEG to the "good"
      hemisphere in children with unihemispheric encephaloclastic lesions. This EEG
      pattern is compatible with seizure free outcome after surgery, provided other
      clinical findings and tests are concordant with origin from the abnormal
      hemisphere.

PMID- 19740719
TI  - Basic mechanisms of MCD in animal models.
AB  - Epilepsy-associated glioneuronal malformations (malformations of cortical
      development [MCD]) include focal cortical dysplasias (FCD) and highly
      differentiated glioneuronal tumors, most frequently gangliogliomas. The
      neuropathological findings are variable but suggest aberrant proliferation,
      migration, and differentiation of neural precursor cells as essential
      pathogenetic elements. Recent advances in animal models for MCDs allow new
      insights in the molecular pathogenesis of these epilepsy-associated lesions.
      Novel approaches, presented here, comprise RNA interference strategies to
      generate and study experimental models of subcortical band heterotopia and study
      functional aspects of aberrantly shaped and positioned neurons. Exciting analyses
      address impaired NMDA receptor expression in FCD animal models compared to human
      FCDs and excitatory imbalances in MCD animal models such as lissencephaly gene
      ablated mice as well as in utero irradiated rats. An improved understanding of
      relevant pathomechanisms will advance the development of targeted treatment
      strategies for epilepsy-associated malformations.

PMID- 19740721
TI  - [Analysis of syphilis and gonorrhoea cases, based on data from the National STD
      Centre, Department of Dermatology and Venerology, Semmelweis University (2005
      2008)].
AB  - The STD Department of Semmelweis University Budapest is the National Centre of
      Hungary, which is responsible for screening and care of sexually transmitted
      diseases (STD), including syphilis and gonorrhoea. 42,114 patients attended the
      STD Department and 25,362 anonymous screening (HIV: 12,337, syphilis: 13,025)
      were done between January 2005 and December 2008. During this period 600
      syphilitic and 339 gonorrhoea infections were diagnosed. The obligatory HIV
      screening of patients with sexually transmitted infections (STI) resulted
      positive result in 47 cases, and 63 patients infected with HIV acquired new
      syphilitic or gonorrhoea infection. Contact tracing was successful in around 400
      syphilis cases, and 150-200 gonorrhoea cases per year. We present our statistical
      data in order to call attention to the resurgence of syphilis and gonorrhoea and
      the importance of STD co-infections.

PMID- 19740722
TI  - [TNF-alpha blocking therapy in chronic inflammatory bowel disease].
AB  - The introduction of TNF-alpha blocking therapy has produced a dramatic change in
      the treatment of therapy resistant patients with inflammatory bowel disease. Both
      infliximab and adalimumab are effective in moderately severe and severe Crohn's
      disease. Besides, infliximab is potent in the remission and its sustaining in
      ulcerative colitis. However, among therapy resistant individuals, 20-30 percents
      of patients with Crohn's disease and 30-40 percents of patients with ulcerative
      colitis do not respond to these treatments. To date, no comparative study between
      the two drugs has been carried out and the clinical trials can not be directly
      compared to each others, still, on the basis of general considerations, there is
      no essential difference in the effectiveness between the two treatments.

PMID- 19740723
TI  - [Hungarians fallen ill abroad: questions of repatriation].
AB  - In the previous part of the paper authors described the repatriation process, the
      complex medical task of the patient returning home from abroad, and in particular
      its most crucial phase, the patient repatriation. Authors reviewed the
      indications and the basic terms of the patient-repatriation. Vehicles and their
      availability for the different type of repatriation modalities were analyzed as
      well. In the second part of the paper, the authors analyze the professional
      aspects and the decision making procedure on the repatriation. Unfortunately,
      sometimes the treating doctor does not realize the minimum terms of the ability
      for the transport of the patient. Therefore he might provide an incorrect
      suggestion on the time and modality of the repatriation. The responsibility of
      the transport belongs to the doctor who makes the decision, and to the medical
      team, who performs the repatriation, respectively. The decision has to be made by
      the doctor of the insurance company, upon detailed and correct medical
      information. When a non-professional person is involved into the decision making,
      patient can be jeopardized; and the repatriation process can be failed. The
      medical transport is a medical activity in Hungary, therefore it must be
      performed according to the medical regulations and to the professional standards,
      the protocols and the transport should be carefully documented. Employees of the
      assistance team of the insurance companies must be familiar with that regulations
      and protocols.

PMID- 19740724
TI  - [Therapeutic modalities in the treatment of palmar and axillary hyperhidrosis].
AB  - The authors summarize their therapeutic methods of palmar and axillary
      hyperhidrosis in this article. They discuss the characteristics, frequency of
      upper limb and patho-anatomical features of chronic sweating. Authors summarized
      their almost 40 years experience in treatment methods, technological improvements
      as well as they review recent knowledge and relevant literature. The open
      thoracotomic desympathization applied in the beginnings was gradually replaced by
      a minimally invasive VATS-sympathectomy (Video Assisted Thoracoscopic Surgery).
      The possibilities of conservative treatments, local excision methods will also be
      discussed, as well as the application and efficiency of Botox-treatments that are
      used in plastic surgery. The mean frequency of 0.1-1.0% described in scientific
      literature is indicative of a significant number of unresolved cases, which thus
      requires more efficient diagnostic and patient orientation practices. Based on
      their experiences, the most efficient treatment of upper limb hyperhidrosis is
      the thoracic sympathectomy (ramicotomy and the relevant T(2) -T(3) ganglia)
      according to Smithwick-procedure and modified by others. If necessary, one-stage
      bilateral VATS-surgery may be applied. Another effective conservative possibility
      is the Botox-therapy, which they had applied individually at the plastic surgery
      clinic. Significant complications or compensatory hyperhidrosis were not
      detected.

PMID- 19740725
TI  - [Centenary of the 16th International Medical Congress held in Budapest].

PMID- 19740728
TI  - [The love of legislation -- Interview with Dr. Gabor Kapocs. Interview by Gyorgyi
      B. Kiraly].

PMID- 19740729
TI  - The use of kinetics as a marker for manual dexterity after stroke and stroke
      recovery.
AB  - Stroke is the leading cause of severe, long-term disability among older adults in
      the United States. Unimanual motor performance of the hemiparetic limb is clearly
      compromised, and these declines are well documented. An often overlooked aspect
      of motor function for patients with stroke is the effect of unilateral motor
      dysfunction on bimanual motor activities. Diminished bimanual function resulting
      from upper extremity hemiparesis necessarily limits the patient's daily
      functioning. In this review we describe a bimanual dexterity task that replicates
      many daily activities and outline how kinetic analysis of this task may provide
      insight into diminished bimanual function of patients with stroke and how these
      variables may be useful in assessing level of recovery and rate of motor recovery
      associated with behavioral interventions intended to improve upper extremity
      function. It is argued that the use of objective kinetic measures to quantify
      hand function may facilitate the clinical adoption of behavioral interventions
      for stroke, such as constraint-induced movement therapy and other repetitive task
      practice-based interventions.

PMID- 19740730
TI  - Gains in upper extremity function after stroke via recovery or compensation:
      Potential differential effects on amount of real-world limb use.
AB  - In terms of integration of the paretic upper extremity in activities of daily
      living (ADLs), outcome is poor after stroke. Furthermore, amount of real-world
      arm use appears only weakly correlated with laboratory motor function scales.
      Therefore, amount of arm use may depend critically on the location, extent, and
      type of functional gains, which can be quantified with comprehensive kinematic
      and EMG analysis of ADL performance. Gains in upper extremity function can occur
      via compensation or recovery of premorbid movement and EMG patterns, and
      traditional treatment approaches encourage adoption of compensatory strategies
      early in the postacute period that can inhibit potential recovery. A new
      treatment approach called Accelerated Skill Acquisition Program (ASAP) focuses on
      impairment reduction coupled with repetitive, task-specific training of the
      paretic arm during ADLs. We present pilot data that show recovery in subjects who
      received the ASAP, while a usual care control subject showed increased use of
      compensation over the same period. Finally, we discuss the advantages of data
      reduction methods such as principal components analysis, confirmatory factor
      analysis, and structural equation modeling, which can potentially distill large
      kinematic and EMG data sets into the key latent variables that predict amount of
      real-world use.

PMID- 19740731
TI  - The corticospinal system and transcranial magnetic stimulation in stroke.
AB  - During the last decades, transcranial magnetic stimulation (TMS) has been used as
      a noninvasive method to investigate motor cortical reorganization and
      neuroplasticity in humans after stroke. An increasing number of studies in the
      field of motor control have used TMS to gain an understanding of the different
      aspects of stroke cortical physiology and motor recovery. This review addresses
      the effects of corticospinal tract (CST) lesions in humans and nonhuman primates
      on the functional organization of the motor system. We review information on the
      physiological mechanisms by which the CST contributes to normal motor control and
      to central nervous system reorganization following stroke when the CST is injured
      as measured using TMS. Insight into these physiological mechanisms has led to the
      development of scientifically sound interventional proposals in the field of
      neurorehabilitation.

PMID- 19740732
TI  - Changes in resting state effective connectivity in the motor network following
      rehabilitation of upper extremity poststroke paresis.
AB  - BACKGROUND: A promising paradigm in human neuroimaging is the study of slow (<0.1
      Hz) spontaneous fluctuations in the hemodynamic response measured by functional
      magnetic resonance imaging (fMRI). Spontaneous activity (i.e., resting state)
      refers to activity that cannot be attributed to specific inputs or outputs, that
      is, activity intrinsically generated by the brain. METHOD: This article presents
      pilot data examining neural connectivity in patients with poststroke hemiparesis
      before and after 3 weeks of upper extremity rehabilitation in the Accelerated
      Skill Acquisition Program (ASAP). Resting-state fMRI data acquired pre and post
      therapy were analyzed using an exploratory adaptation of structural equation
      modeling (SEM) to evaluate therapy-related changes in motor network effective
      connectivity. RESULTS: Each ASAP patient showed behavioral improvement. ASAP
      patients also showed increased influence of the affected hemisphere premotor
      cortex (a-PM) upon the unaffected hemisphere premotor cortex (u-PM) following
      therapy. The influence of a-PM on affected hemisphere primary motor cortex (a-M1)
      also increased with therapy for 3 of 5 patients, including those with greatest
      behavioral improvement. CONCLUSIONS: Our findings suggest that network analyses
      of resting-state fMRI constitute promising tools for functional characterization
      of functional brain disorders, for intergroup comparisons, and potentially for
      assessing effective connectivity within single subjects; all of which have
      important implications for stroke rehabilitation.

PMID- 19740734
TI  - The prevalence of injury for stroke caregivers and associated risk factors.
AB  - BACKGROUND: A vast body of research has shown that the emotional and physical
      demands of caregiving may lead to increased stress and burden. However, it is
      unknown whether these factors are associated with increased risk for injuries
      among caregivers. PURPOSE: Stroke survivors and their caregivers (N = 275) were
      surveyed using existing measures to explore the prevalence of physical injuries
      among caregivers and the types of injuries and factors associated with caregiver
      injury. METHODS: Caregiver measures included items from the National Alliance for
      Caregiving (NAC) survey and the short form of the Center for Epidemiologic
      Studies Depression Scale (CES-D). Veterans completed items on health and
      functioning from the Behavioral Risk Factors Surveillance Survey (BRFSS).
      RESULTS: We found that stroke caregivers who experience high burden levels and/or
      depression are considerably more likely to experience an increased risk for
      injury. Further, the vast majority of injured caregivers indicated that their
      injury interfered with their ability to provide care for the veteran. CONCLUSION:
      This suggests that injury on the part of the family caregiver may lead to the
      veteran's placement in a skilled nursing facility and lead to increased costs for
      the Department of Veteran's Affairs.

PMID- 19740735
TI  - Single point mutations in the small cytoplasmic loop of ACA8, a plasma membrane
      Ca2+-ATPase of Arabidopsis thaliana, generate partially deregulated pumps.
AB  - ACA8 is a type 2B Ca(2+)-ATPase having a regulatory N terminus whose auto
      inhibitory action can be suppressed by binding of calmodulin (CaM) or of acidic
      phospholipids. ACA8 N terminus is able to interact with a region of the small
      cytoplasmic loop connecting transmembrane domains 2 and 3. To determine the role
      of this interaction in auto-inhibition we analyzed single point mutants produced
      by mutagenesis of ACA8 Glu(252) to Asn(345) sequence. Mutation to Ala of any of
      six tested acidic residues (Glu(252), Asp(273), Asp(291), Asp(303), Glu(302), or
      Asp(332)) renders an enzyme that is less dependent on CaM for activity. These
      results highlight the relevance in ACA8 auto-inhibition of a negative charge of
      the surface area of the small cytoplasmic loop. The most deregulated of these
      mutants is D291A ACA8, which is less activated by controlled proteolysis or by
      acidic phospholipids; the D291A mutant has an apparent affinity for CaM higher
      than wild-type ACA8. Moreover, its phenotype is stronger than that of D291N ACA8,
      suggesting a more direct involvement of this residue in the mechanism of auto
      inhibition. Among the other produced mutants (I284A, N286A, P289A, P322A, V344A,
      and N345A), only P322A ACA8 is less dependent on CaM for activity than the wild
      type. The results reported in this study provide the first evidence that the
      small cytoplasmic loop of a type 2B Ca(2+)-ATPase plays a role in the attainment
      of the auto-inhibited state.

PMID- 19740733
TI  - Brain plasticity and genetic factors.
AB  - Brain plasticity refers to changes in brain function and structure that arise in
      a number of contexts. One area in which brain plasticity is of considerable
      interest is recovery from stroke, both spontaneous and treatment-induced. A
      number of factors influence these poststroke brain events. The current review
      considers the impact of genetic factors. Polymorphisms in the human genes coding
      for brain-derived neurotrophic factor (BDNF) and apolipoprotein E (ApoE) have
      been studied in the context of plasticity and/or stroke recovery and are
      discussed here in detail. Several other genetic polymorphisms are indirectly
      involved in stroke recovery through their modulating influences on processes such
      as depression and pharmacotherapy effects. 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 stroke.

PMID- 19740736
TI  - Distinct amino termini of two human HCS isoforms influence biotin acceptor
      substrate recognition.
AB  - The human holocarboxylase synthetase (HCS) catalyzes transfer of biotin to biotin
      dependent carboxylases, and the enzyme is therefore of fundamental importance for
      many physiological processes, including fatty acid synthesis, gluconeogenesis,
      and amino acid catabolism. In addition, the enzyme functions in regulating
      transcription initiation at several genes that code for proteins involved in
      biotin metabolism. Two major forms of HCS exist in humans, which differ at the
      amino terminus by 57 amino acids. In this work, the two proteins were expressed
      in Escherichia coli, purified, and subjected to biochemical characterization.
      Equilibrium sedimentation indicates that the two proteins are monomers both in
      their apo-forms and when bound to the enzymatic intermediate biotinyl 5'-AMP.
      Steady state kinetic analyses as a function of biotin, ATP, or a minimal biotin
      accepting substrate concentration indicate similar behaviors for both isoforms.
      However, pre-steady state analysis of biotin transfer reveals that the full
      length HCS associates with the minimal biotin acceptor substrate with a rate
      twice as fast as that of the truncated isoform. These results are consistent with
      a role for the HCS amino terminus in biotin acceptor substrate recognition.

PMID- 19740737
TI  - Uptake of oxidized low density lipoprotein by CD36 occurs by an actin-dependent
      pathway distinct from macropinocytosis.
AB  - The class B scavenger receptor CD36 has numerous ligands that include modified
      forms of low density lipoprotein, fibrillar amyloid, apoptotic cells, and
      Plasmodium falciparum-infected red blood cells, linking this molecule to
      atherosclerosis, Alzheimer disease, malaria, and other diseases. We studied the
      signaling events that follow receptor engagement and lead to CD36 and ligand
      internalization. We show that oxidized low density lipoprotein or antibody
      induced clustering of CD36 triggers macropinocytosis and internalization of the
      receptor-ligand complex. Remarkably, however, CD36 internalization is independent
      of macropinocytosis and occurs by a novel endocytic mechanism that depends on
      actin, but not dynamin. This actin-driven endocytosis requires the activation Src
      family kinases, JNK, and Rho family GTPases, but, unlike macropinocytosis, it is
      not affected by inhibitors of phosphatidylinositol 3-kinase or Na/H exchange.
      Manipulation of this unique mode of internalization may prove helpful in the
      prevention and management of the wide range of diseases in which CD36 is
      implicated.

PMID- 19740738
TI  - Insulin-stimulated phosphorylation of the Rab GTPase-activating protein TBC1D1
      regulates GLUT4 translocation.
AB  - Insulin stimulates the translocation of the glucose transporter GLUT4 from
      intracellular locations to the plasma membrane in adipose and muscle cells. Prior
      studies have shown that Akt phosphorylation of the Rab GTPase-activating protein,
      AS160 (160-kDa Akt substrate; also known as TBC1D4), triggers GLUT4
      translocation, most likely by suppressing its Rab GTPase-activating protein
      activity. However, the regulation of a very similar protein, TBC1D1 (TBC domain
      family, member 1), which is mainly found in muscle, in insulin-stimulated GLUT4
      translocation has been unclear. In the present study, we have identified likely
      Akt sites of insulin-stimulated phosphorylation of TBC1D1 in C2C12 myotubes. We
      show that a mutant of TBC1D1, in which several Akt sites have been converted to
      alanine, is considerably more inhibitory to insulin-stimulated GLUT4
      translocation than wild-type TBC1D1. This result thus indicates that similar to
      AS160, Akt phosphorylation of TBC1D1 enables GLUT4 translocation. We also show
      that in addition to Akt activation, activation of the AMP-dependent protein
      kinase partially relieves the inhibition of GLUT4 translocation by TBC1D1.
      Finally, we show that the R125W variant of TBC1D1, which has been genetically
      associated with obesity, is equally inhibitory to insulin-stimulated GLUT4
      translocation, as is wild-type TBC1D1, and that healthy and type 2 diabetic
      individuals express approximately the same level of TBC1D1 in biopsies of vastus
      lateralis muscle. In conclusion, phosphorylation of TBC1D1 is required for GLUT4
      translocation. Thus, the regulation of TBC1D1 resembles that of its paralog,
      AS160.

PMID- 19740739
TI  - Zfp206, Oct4, and Sox2 are integrated components of a transcriptional regulatory
      network in embryonic stem cells.
AB  - Zfp206 (recently renamed Zscan10) encodes a zinc finger transcription factor
      specifically expressed in human and mouse embryonic stem cells (ESC). It has been
      shown that Zfp206 is required to maintain ESC in an undifferentiated, pluripotent
      state. Presented here are data showing that Zfp206 works together with two other
      transcription factors, Oct4 and Sox2, which are also essential regulators of ESC
      pluripotency. We show that Zfp206 binds to the Oct4 promoter and directly
      regulates Oct4 expression. Genome-wide mapping of Zfp206-binding sites in ESC
      identifies more than 3000 target genes, many of which encode transcription
      factors that are also targeted for regulation by Oct4 and Sox2. In addition, we
      show that Zfp206 physically interacts with both Oct4 and Sox2. These data
      demonstrate that Zfp206 is a key component of the core transcriptional regulatory
      network and together with Oct4 and Sox2 regulates differentiation of ESC.

PMID- 19740740
TI  - Plastid alternative oxidase (PTOX) promotes oxidative stress when overexpressed
      in tobacco.
AB  - Photoinhibition and production of reactive oxygen species were studied in tobacco
      plants overexpressing the plastid terminal oxidase (PTOX). In high light, these
      plants was more susceptible to photoinhibition than wild-type plants. Also oxygen
      evolving activity of isolated thylakoid membranes from the PTOX-overexpressing
      plants was more strongly inhibited in high light than in thylakoids from wild
      type plants. In contrast in low light, in the PTOX overexpressor, the thylakoids
      were protected against photoinhibition while in wild type they were significantly
      damaged. The production of superoxide and hydroxyl radicals was shown by EPR spin
      trapping techniques in the different samples. Superoxide and hydroxyl radical
      production was stimulated in the overexpressor. Two-thirds of the superoxide
      production was maintained in the presence of DNP-INT, an inhibitor of the
      cytochrome b(6)f complex. No increase of the SOD content was observed in the
      overexpressor compared with the wild type. We propose that superoxide is produced
      by PTOX in a side reaction and that PTOX can only act as a safety valve under
      stress conditions when the generated superoxide is detoxified by an efficient
      antioxidant system.

PMID- 19740741
TI  - Direct regulation of prokaryotic Kir channel by cholesterol.
AB  - Our earlier studies have shown that channel activity of Kir2 subfamily of inward
      rectifiers is strongly suppressed by the elevation of cellular cholesterol. The
      goal of this study is to determine whether cholesterol suppresses Kir channels
      directly. To achieve this goal, purified prokaryotic Kir (KirBac1.1) channels
      were incorporated into liposomes of defined lipid composition, and channel
      activity was assayed by (86)Rb(+) uptake. Our results show that (86)Rb(+) flux
      through KirBac1.1 is strongly inhibited by cholesterol. Incorporation of 5% (mass
      cholesterol/phospholipid) cholesterol into the liposome suppresses (86)Rb(+) flux
      by >50%, and activity is completely inhibited at 12-15%. However, epicholesterol,
      a stereoisomer of cholesterol with similar physical properties, has significantly
      less effect on KirBac-mediated (86)Rb(+) uptake than cholesterol. Furthermore,
      analysis of multiple sterols suggests that cholesterol-induced inhibition of
      KirBac1.1 channels is mediated by specific interactions rather than by changes in
      the physical properties of the lipid bilayer. In contrast to the inhibition of
      KirBac1.1 activity, cholesterol had no effect on the activity of reconstituted
      KscA channels (at up to 250 microg/mg of phospholipid). Taken together, these
      observations demonstrate that cholesterol suppresses Kir channels in a pure
      protein-lipid environment and suggest that the interaction is direct and
      specific.

PMID- 19740742
TI  - Analysis of PTEN complex assembly and identification of heterogeneous nuclear
      ribonucleoprotein C as a component of the PTEN-associated complex.
AB  - PTEN (phosphatase and tensin homolog deleted on chromosome 10) is well
      characterized for its role in antagonizing the phosphoinositide 3-kinase pathway.
      Previous studies using size-exclusion chromatography demonstrated PTEN
      recruitment into high molecular mass complexes and hypothesized that PTEN
      phosphorylation status and PDZ binding domain may be required for such complex
      formation. In this study, we set out to test the structural requirements for PTEN
      complex assembly and identify the component(s) of the PTEN complex(es). Our
      results demonstrated that the PTEN catalytic function and PDZ binding domain are
      not absolutely required for its complex formation. On the other hand, PTEN
      phosphorylation status has a significant impact on its complex assembly. Our
      results further demonstrate enrichment of the PTEN complex in nuclear lysates,
      suggesting a mechanism through which PTEN phosphorylation may regulate its
      complex assembly. These results prompted further characterization of other
      protein components within the PTEN complex(es). Using size-exclusion
      chromatography and two-dimensional difference gel electrophoresis followed by
      mass spectrometry analysis, we identified heterogeneous nuclear ribonucleoprotein
      C (hnRNP C) as a novel protein recruited to higher molecular mass fractions in
      the presence of PTEN. Further analysis indicates that endogenous hnRNP C and PTEN
      interact and co-localize within the nucleus, suggesting a potential role for
      PTEN, alongside hnRNP C, in RNA regulation.

PMID- 19740743
TI  - Curcumin cross-links cystic fibrosis transmembrane conductance regulator (CFTR)
      polypeptides and potentiates CFTR channel activity by distinct mechanisms.
AB  - Cystic fibrosis (CF) is caused by loss-of-function mutations in the CFTR chloride
      channel. Wild type and mutant CFTR channels can be activated by curcumin, a well
      tolerated dietary compound with some appeal as a prospective CF therapeutic.
      However, we show here that curcumin has the unexpected effect of cross-linking
      CFTR polypeptides into SDS-resistant oligomers. This effect occurred for CFTR
      channels in microsomes as well as in intact cells and at the same concentrations
      that are effective for promoting CFTR channel activity (5-50 mum). Both mature
      CFTR polypeptides at the cell surface and immature CFTR protein in the
      endoplasmic reticulum were cross-linked by curcumin, although the latter pool was
      more susceptible to this modification. Curcumin cross-linked two CF mutant
      channels (Delta F508 and G551D) as well as a variety of deletion constructs that
      lack the major cytoplasmic domains. In vitro cross-linking could be prevented by
      high concentrations of oxidant scavengers (i.e. reduced glutathione and sodium
      azide) indicating a possible oxidation reaction with the CFTR polypeptide.
      Importantly, cyclic derivatives of curcumin that lack the reactive beta diketone
      moiety had no cross-linking activity. One of these cyclic derivatives stimulated
      the activities of wild type CFTR channels, Delta 1198-CFTR channels, and G551D
      CFTR channels in excised membrane patches. Like the parent compound, the cyclic
      derivative irreversibly activated CFTR channels in excised patches during
      prolonged exposure (>5 min). Our results raise a note of caution about secondary
      biochemical effects of reactive compounds like curcumin in the treatment of CF.
      Cyclic curcumin derivatives may have better therapeutic potential in this regard.

PMID- 19740744
TI  - Copper-dependent recycling of hCTR1, the human high affinity copper transporter.
AB  - Copper is an essential co-factor in many important physiological processes, but
      at elevated levels it is toxic to cells. Thus at both the organism and cellular
      level mechanisms have evolved to finely tune copper homeostasis. The protein
      responsible for copper entry from the circulation in most human cells is hCTR1, a
      small protein (190 amino acid residues) that functions as a trimer in the plasma
      membrane. In the present work we employ cell surface biotinylation and isotopic
      copper uptake studies of overexpressed hCTR1 in HEK293 cells to examine the acute
      (minutes) response of hCTR1 to changes in extracellular copper. We show that
      within 10 min of exposure to copper at 2.5 microM or higher, plasma membrane
      hCTR1 levels are reduced (by approximately 40%), with a concomitant reduction in
      copper uptake rates. We are unable to detect any degradation of internalized
      hCTR1 in the presence of cycloheximide after up to 2 h of exposure to 0-100
      microM copper. Using a reversible biotinylation assay, we quantified internalized
      hCTR1, which increased upon the addition of copper and corresponded to the hCTR1
      lost from the surface. In addition, when extracellular copper is then removed,
      internalized hCTR1 is promptly (within 30 min) recycled to the plasma membrane.
      We have shown that in the absence of added extracellular copper, there is a small
      but detectable amount of internalized hCTR1 that is increased in the presence of
      copper. Similar studies on endogenous hCTR1 show a cell-specific response to
      elevated extracellular copper. Copper-dependent internalization and recycling of
      hCTR1 provides an acute and reversible mechanism for the regulation of cellular
      copper entry.

PMID- 19740745
TI  - A truncated form of p23 down-regulates telomerase activity via disruption of
      Hsp90 function.
AB  - The Hsp90-associated protein p23 modulates Hsp90 activity during the final stages
      of the chaperone pathway to facilitate maturation of client proteins. Previous
      reports indicate that p23 cleavage induced by caspases during cell death triggers
      destabilization of client proteins. However, the specific role of truncated p23
      (Delta p23) in this process and the underlying mechanisms remain to be
      determined. One such client protein, hTERT, is a telomerase catalytic subunit
      regulated by several chaperone proteins, including Hsp90 and p23. In the present
      study, we examined the effects of p23 cleavage on hTERT stability and telomerase
      activity. Our data showed that overexpression of Delta p23 resulted in a decrease
      in hTERT levels, and a down-regulation in telomerase activity. Serine
      phosphorylation of Hsp90 was significantly reduced in cells expressing high
      levels of Delta p23 compared with those expressing full-length p23. Mutation
      analyses revealed that two serine residues (Ser-231 and Ser-263) in Hsp90 are
      important for activation of telomerase, and down-regulation of telomerase
      activity by Delta p23 was associated with inhibition of cell growth and
      sensitization of cells to cisplatin. Our data aid in determining the mechanism
      underlying the regulation of telomerase activity by the chaperone complex during
      caspase-dependent cell death.

PMID- 19740746
TI  - Crystal structure and function of a DARPin neutralizing inhibitor of lactococcal
      phage TP901-1: comparison of DARPin and camelid VHH binding mode.
AB  - Combinatorial libraries of designed ankyrin repeat proteins (DARPins) have been
      proven to be a valuable source of specific binding proteins, as they can be
      expressed at very high levels and are very stable. We report here the selection
      of DARPins directed against a macromolecular multiprotein complex, the baseplate
      BppUxBppL complex of the lactococcal phage TP901-1. Using ribosome display, we
      selected several DARPins that bound specifically to the tip of the receptor
      binding protein (RBP, the BppL trimer). The three selected DARPins display high
      specificity and affinity in the low nanomolar range and bind with a stoichiometry
      of one DARPin per BppL trimer. The crystal structure of a DARPin complexed with
      the RBP was solved at 2.1 A resolution. The DARPinxRBP interface is of the
      concave (DARPin)-convex (RBP) type, typical of other DARPin protein complexes and
      different from what is observed with a camelid VHH domain, which penetrates the
      phage p2 RBP inter-monomer interface. Finally, phage infection assays
      demonstrated that TP901-1 infection of Lactococcus lactis cells was inhibited by
      each of the three selected DARPins. This study provides proof of concept for the
      possible use of DARPins to circumvent viral infection. It also provides support
      for the use of DARPins in co-crystallization, due to their rigidity and their
      ability to provide multiple crystal contacts.

PMID- 19740747
TI  - ID2 (inhibitor of DNA binding 2) is a rhythmically expressed transcriptional
      repressor required for circadian clock output in mouse liver.
AB  - Id2 is a helix-loop-helix transcription factor gene expressed in a circadian
      manner in multiple tissues with a phase-locked relationship with canonical clock
      genes. Our previous studies have identified circadian phenotypes in Id2 null
      mice, including enhanced photo-entrainment and disruption of activity rhythms,
      and have demonstrated a potent inhibitory effect of ID proteins upon CLOCK-BMAL1
      transactivation of clock gene and clock-controlled gene activity. We have now
      begun to explore the potential role that ID2 may play in specifically regulating
      clock output. Here we show that ID2 protein is rhythmically expressed in mouse
      liver. Time-of-day-specific liver gene expression in Id2(+/+) and Id2(-/-) mice
      under circadian conditions was studied using DNA microarray analysis, identifying
      651 differentially expressed genes, including a subset of 318 genes deemed
      rhythmically expressed in other studies. Examination of individual time courses
      reveals that these genes are dysregulated in a highly time-specific manner. A
      cohort of different functional groups were identified, including genes associated
      with glucose and lipid metabolism, e.g. serum protein Igfbp1 and lipoprotein
      lipase. We also reveal that the Id2(-/-) mice show a reduction in lipid storage
      in the liver and white adipose tissue, suggesting that disruption of normal
      circadian activity of components of lipid metabolism can result in overt
      physiological alterations. These data reveal a role for the transcriptional
      repressor ID2 as a circadian output regulator in the periphery.

PMID- 19740749
TI  - A novel biosynthetic pathway of archaetidyl-myo-inositol via archaetidyl-myo
      inositol phosphate from CDP-archaeol and D-glucose 6-phosphate in methanoarchaeon
      Methanothermobacter thermautotrophicus cells.
AB  - Ether-type inositol phospholipids are ubiquitously distributed in Archaea
      membranes. The present paper describes a novel biosynthetic pathway of the
      archaeal inositol phospholipid. To study the biosynthesis of archaetidylinositol
      in vitro, we prepared two possible substrates: CDP-archaeol, which was chemically
      synthesized, and myo-[(14)C]inositol 1-phosphate, which was enzymatically
      prepared from [(14)C]glucose 6-phosphate with the inositol 1-phosphate (IP)
      synthase of this organism. The complete structure of the IP synthase reaction
      product was determined to be 1l-myo-inositol 1-phosphate, based on gas liquid
      chromatography with a chiral column. When the two substrates were incubated with
      the Methanothermobacter thermautotrophicus membrane fraction, archaetidylinositol
      phosphate (AIP) was formed along with a small amount of archaetidylinositol (AI).
      The two products were identified by fast atom bombardment-mass spectrometry and
      chemical analyses. AI was formed from AIP by incubation with the membrane
      fraction, but AIP was not formed from AI. This finding indicates that archaeal AI
      was synthesized from CDP-archaeol and d-glucose 6-phosphate via myo-inositol 1
      phosphate and AIP. Although the relevant enzymes were not isolated, three enzymes
      are implied: IP synthase, AIP synthase, and AIP phosphatase. AIP synthase was
      homologous to yeast phosphatidylinositol synthase, and we confirmed AIP synthase
      activity by cloning the encoding gene (MTH1691) and expressing it in Escherichia
      coli. AIP synthase is a newly found member of the enzyme superfamily CDP-alcohol
      phosphatidyltransferase, which includes a wide range of enzymes that attach polar
      head groups to ester- and ether-type phospholipids of bacterial and archaeal
      origin. This is the first report of the biosynthesis of ether-type inositol
      phospholipids in Archaea.

PMID- 19740748
TI  - FoxO1 and HNF-4 are involved in regulation of hepatic glucokinase gene expression
      by resveratrol.
AB  - Resveratrol, a polyphenol derived from grapes, exerts important effects on
      glucose and lipid metabolism, yet detailed mechanisms mediating these effects
      remain unknown. The liver plays a central role in energy homeostasis, and
      glucokinase (GK) is a key enzyme involved in glucose utilization. Resveratrol
      activates SIRT1 (sirtuin 1), which promotes deacetylation of the forkhead
      transcription factor FoxO1. Previously, we reported that FoxO1 can suppress and
      that HNF-4 can stimulate GK expression in the liver. Here, we examined the role
      of FoxO1 and HNF-4 in mediating resveratrol effects on liver GK expression.
      Resveratrol suppressed hepatic GK expression in vivo and in isolated hepatocytes,
      and knocking down FoxO1 with shRNAs disrupted this effect. Reporter gene, gel
      shift, supershift assay, and chromatin immunoprecipitation studies show that
      FoxO1 binds to the GK promoter and that the interplay between FoxO1 and HNF-4
      within the GK promoter is essential for mediating the effects of resveratrol.
      Resveratrol promotes deacetylation of FoxO1 and enhances its recruitment to the
      FoxO-binding element. Conversely, resveratrol suppresses recruitment of HNF-4 to
      its binding site, and knockdown of FoxO1 blocks this effect of resveratrol.
      Coprecipitation and chromatin immunoprecipitation studies show that resveratrol
      enhances interaction between FoxO1 and HNF-4, reduces binding of HNF-4 to its own
      site, and promotes its recruitment to the FoxO site in a FoxO1-dependent manner.
      These results provide the first evidence that resveratrol represses GK expression
      via FoxO1 and that the interaction between FoxO1 and HNF-4 contributes to these
      effects of resveratrol.

PMID- 19740750
TI  - Glucocorticoids and thiazolidinediones interfere with adipocyte-mediated
      macrophage chemotaxis and recruitment.
AB  - The link between intra-abdominal adiposity and type II diabetes has been known
      for decades, and adipose tissue macrophage (ATM)-associated inflammation has
      recently been linked to insulin resistance. However, the mechanisms associated
      with ATM recruitment remain ill defined. Herein, we describe in vitro chemotaxis
      studies, in which adipocyte conditioned medium was used to stimulate macrophage
      migration. We demonstrate that tumor necrosis factor alpha and free fatty acids,
      key inflammatory stimuli involved in obesity-associated autocrine/paracrine
      inflammatory signaling, stimulate adipocyte expression and secretion of
      macrophage chemoattractants. Pharmacological studies showed that peroxisome
      proliferator-activated receptor gamma agonists and glucocorticoids potently
      inhibit adipocyte- induced recruitment of macrophages. This latter effect was
      mediated by the glucocorticoid receptor, which led to decreased chemokine
      secretion and expression. In vivo results were quite comparable; treatment of
      high fat diet-fed mice with dexamethasone prevented ATM accumulation in
      epididymal fat. This decrease in ATM was most pronounced for the proinflammatory
      F4/80(+), CD11b(+), CD11c(+) M-1-like ATM subset. Overall, our results elucidate
      a beneficial function of peroxisome proliferator-activated receptor gamma
      activation and glucocorticoid receptor/glucocorticoids in adipose tissue and
      indicate that pharmacologic prevention of ATM accumulation could be beneficial.

PMID- 19740751
TI  - Characterization of calumenin-SERCA2 interaction in mouse cardiac sarcoplasmic
      reticulum.
AB  - Calumenin is a multiple EF-hand Ca(2+)-binding protein localized in the
      sarcoplasmic reticulum (SR) with C-terminal SR retention signal HDEF. Recently,
      we showed evidence that calumenin interacts with SERCA2 in rat cardiac SR (Sahoo,
      S. K., and Kim, D. H. (2008) Mol. Cells 26, 265-269). The present study was
      undertaken to further characterize the association of calumenin with SERCA2 in
      mouse heart by various gene manipulation approaches. Immunocytochemical analysis
      showed that calumenin and SERCA2 were partially co-localized in HL-1 cells.
      Knockdown (KD) of calumenin was conducted in HL-1 cells and 80% reduction of
      calumenin did not induce any expressional changes of other Ca(2+)-cycling
      proteins. But it enhanced Ca(2+) transient amplitude and showed shortened time to
      reach peak and decreased time to reach 50% of baseline. Oxalate-supported Ca(2+)
      uptake showed increased Ca(2+) sensitivity of SERCA2 in calumenin KD HL-1 cells.
      Calumenin and SERCA2 interaction was significantly lower in the presence of
      thapsigargin, vanadate, or ATP, as compared with 1.3 mum Ca(2+), suggesting that
      the interaction is favored in the E1 state of SERCA2. A glutathione S-transferase
      pulldown assay of calumenin deletion fragments and SERCA2 luminal domains
      suggested that regions of 132-222 amino acids of calumenin and 853-892 amino
      acids of SERCA2-L4 are the major binding partners. On the basis of our in vitro
      binding data and available information on three-dimensional structure of Ca(2+)
      ATPases, a molecular model was proposed for the interaction between calumenin and
      SERCA2. Taken together, the present results suggest that calumenin is a novel
      regulator of SERCA2, and its expressional changes are tightly coupled with Ca(2+)
      cycling of cardiomyocytes.

PMID- 19740752
TI  - Mal3 masks catastrophe events in Schizosaccharomyces pombe microtubules by
      inhibiting shrinkage and promoting rescue.
AB  - Schizosaccharomyces pombe Mal3 is a member of the EB family of proteins, which
      are proposed to be core elements in a tip-tracking network that regulates
      microtubule dynamics in cells. How Mal3 itself influences microtubule dynamics is
      unclear. We tested the effects of full-length recombinant Mal3 on dynamic
      microtubules assembled in vitro from purified S. pombe tubulin, using dark field
      video microscopy to avoid fluorescent tagging and data-averaging techniques to
      improve spatiotemporal resolution. We find that catastrophe occurs stochastically
      as a fast (<2.2 s) transition from constant speed growth to constant speed
      shrinkage with a constant probability that is independent of the Mal3
      concentration. This implies that Mal3 neither stabilizes nor destabilizes
      microtubule tips. Mal3 does, however, stabilize the main part of the microtubule
      lattice, inhibiting shrinkage and increasing the frequency of rescues, consistent
      with recent models in which Mal3 on the lattice forms stabilizing lateral links
      between neighboring protofilaments. At high concentrations, Mal3 can entirely
      block shrinkage and induce very rapid rescue, making catastrophes impossible to
      detect, which may account for the apparent suppression of catastrophe by Mal3 and
      other EBs in vivo. Overall, we find that Mal3 stabilizes microtubules not by
      preventing catastrophe at the microtubule tip but by inhibiting lattice
      depolymerization and enhancing rescue. We argue that this implies that Mal3 binds
      microtubules in different modes at the tip and on the lattice.

PMID- 19740753
TI  - Bombyx mori homologs of STIM1 and Orai1 are essential components of the signal
      transduction cascade that regulates sex pheromone production.
AB  - Sex pheromone production in the pheromone gland (PG) of the silkmoth, Bombyx
      mori, is mediated by store-operated channels (SOCs) acting downstream of
      pheromone biosynthesis activating neuropeptide (PBAN) binding. Although recent
      studies have implicated STIM1 and Orai1 as essential components of SOCs, little
      is known about the molecular nature of the SOCs involved in sex pheromone
      production. In this study we cloned silkmoth homologs of STIM1 and Orai1 and
      sought to determine whether they comprise the PG SOC pathway. BmSTIM1 is
      expressed in multiple tissues and, in the PG, is encoded by two transcripts of
      differing size. BmOrai1A and BmOrai1B, which are identical except for a 37
      residue N-terminal truncation in BmOrai1B, arise from alternative splicing of the
      bmorai1 locus and are expressed as independent transcripts in various tissues. In
      the PG, only BmOrai1B is actively transcribed. Fluorescent chimeras demonstrated
      that BmSTIM1 expression is restricted to the endoplasmic reticulum, whereas both
      BmOrai1A and BmOrai1B localize to the cell surface. In Ca(2+)-free medium,
      thapsigargin-mediated depletion of endoplasmic reticulum Ca(2+) stores resulted
      in redistribution of BmSTIM1 to the plasma membrane, but only when the BmOrai1
      homologs were also overexpressed. Translocation was dependent on the BmSTIM1 C
      terminus "CRAC activation domain." Ala mutation of Lys(380), Lys(383), Lys(384),
      Arg(382), and Arg(385) suggests that translocation involves electrostatic
      interactions. Translocation was also seen following PBAN stimulation in cells co
      expressing BmSTIM1, BmOrai1B, and the PBAN receptor. In vivo RNA interference
      mediated knockdown of BmSTIM1 and BmOrai1 significantly reduced sex pheromone
      production without affecting cell viability.

PMID- 19740754
TI  - Structural insights into the mechanism of the allosteric transitions of
      Mycobacterium tuberculosis cAMP receptor protein.
AB  - The cAMP receptor protein (CRP) from Mycobacterium tuberculosis is a cAMP
      responsive global transcriptional regulator, responsible for the regulation of a
      multitude of diverse proteins. We have determined the crystal structures of the
      CRP.cAMP and CRP.N(6)-cAMP derivative-bound forms of the enzyme to 2.2- and 2.3 A
      resolution, respectively, to investigate cAMP-mediated conformational and
      structural changes. The allosteric switch from the open, inactive conformation to
      the closed, active conformation begins with a number of changes in the ligand
      binding cavity upon cAMP binding. These subtle structural changes and numerous
      non-bonding interactions between cAMP, the N-domain residues, and the C-domain
      helices demonstrate that the N-domain hairpin loop acts as a structural mediator
      of the allosteric switch. Based on the CRP.N(6)-cAMP crystal structure, binding
      of N(6)-cAMP with a bulkier methylphenylethyl extension from the N6 atom
      stabilizes the cAMP-binding domain, N-domain hairpin, and C-terminal domain in a
      similar manner as that of the CRP.cAMP structure, maintaining structural
      integrity within the subunits. However, the bulkier N6 extension of N(6)-cAMP (in
      R conformation) is accommodated only in subunit A with minor changes, whereas in
      subunit B, the N6 extension is in the S conformation hindering the hinge region
      of the central helix. As a result, the entire N-domain and the C-domain of
      subunit B integrated by the cAMP portion of this ligand, together tilt away (
      approximately 7 degrees tilt) from central helix C, positioning the helix-turn
      helix motif in an unfavorable position for the DNA substrate, asymmetrically.
      Together, these crystal structures demonstrate the mechanism of action of the
      cAMP molecule and its role in integrating the active CRP structure.

PMID- 19740755
TI  - Modulation of nucleotide excision repair by mammalian SWI/SNF chromatin
      remodeling complex.
AB  - Accessibility within chromatin is an important factor in the prompt removal of UV
      induced DNA damage by nucleotide excision repair (NER). Chromatin remodeling by
      the SWI/SNF complex has been shown to play an important modulating role in NER in
      vitro and yeast in vivo. Nevertheless, the molecular basis of cross-talk between
      SWI/SNF and NER in mammalian cells is not fully understood. Here, we show that
      knockdown of Brg1, the ATPase subunit of SWI/SNF, negatively affects the
      elimination of cyclobutane pyrimidine dimers (CPD), but not of pyrimidine (6,
      4)pyrimidone photoproducts (6-4PP) following UV irradiation of mammalian cells.
      Brg1-deficient cells exhibit a lower chromatin relaxation as well as impaired
      recruitment of downstream NER factors, XPG and PCNA, to UV lesions. However, the
      assembly of upstream NER factors, DDB2 and XPC, at the damage site was unaffected
      by Brg1 knockdown. Interestingly, Brg1 interacts with XPC within chromatin and is
      recruited to UV-damaged sites in a DDB2- and XPC-dependent manner. Also,
      postirradiation decrease of XPC levels occurred more rapidly in Brg1-deficient
      than normal cells. Conversely, XPC transcription remained unaltered upon Brg1
      knockdown indicating that Brg1 affects the stability of XPC protein following
      irradiation. Thus, Brg1 facilitates different stages of NER by initially
      modulating UV-induced chromatin relaxation and stabilizing XPC at the damage
      sites, and subsequently stimulating the recruitment of XPG and PCNA to
      successfully culminate the repair.

PMID- 19740756
TI  - Sequence-specific recognition of DNA by the C-terminal domain of nucleoid
      associated protein H-NS.
AB  - The molecular determinants necessary and sufficient for recognition of its
      specific DNA target are contained in the C-terminal domain (H-NSctd) of nucleoid
      associated protein H-NS. H-NSctd protects from DNaseI cleavage a few short DNA
      segments of the H-NS-sensitive hns promoter whose sequences closely match the
      recently identified H-NS consensus motif (tCG(t/a)T(a/t)AATT) and, alone or fused
      to the protein oligomerization domain of phage lambda CI repressor, inhibits
      transcription from the hns promoter in vitro and in vivo. The importance of H-NS
      oligomerization is indicated by the fact that with an extended hns promoter
      construct (400 bp), which allows protein oligomerization, DNA binding and
      transcriptional repression are highly and almost equally efficient with native H
      NS and H-NSctd::lambdaCI and much less effective with the monomeric H-NSctd. With
      a shorter (110 bp) construct, which does not sustain extensive protein
      oligomerization, transcriptional repression is less effective, but native H-NS, H
      NSctd::lambdaCI, and monomeric H-NSctd have comparable activity on this
      construct. The specific H-NS-DNA interaction was investigated by NMR spectroscopy
      using monomeric H-NSctd and short DNA duplexes encompassing the H-NS target
      sequence of hns (TCCTTACATT) with the best fit (8 of 10 residues) to the H-NS
      binding motif. H-NSctd binds specifically and with high affinity to the chosen
      duplexes via an overall electropositive surface involving four residues
      (Thr(109), Arg(113), Thr(114), and Ala(116)) belonging to the same protein loop
      and Glu(101). The DNA target is recognized by virtue of its sequence and of a TpA
      step that confers a structural irregularity to the B-DNA duplex.

PMID- 19740757
TI  - Dual role of DNA in regulating ATP hydrolysis by the SopA partition protein.
AB  - In bacteria, mitotic stability of plasmids and many chromosomes depends on
      replicon-specific systems, which comprise a centromere, a centromere-binding
      protein and an ATPase. Dynamic self-assembly of the ATPase appears to enable
      active partition of replicon copies into cell-halves, but for Walker-box
      partition ATPases the molecular mechanism is unknown. ATPase activity appears to
      be essential for this process. DNA and centromere-binding proteins are known to
      stimulate the ATPase activity but molecular details of the stimulation mechanism
      have not been reported. We have investigated the interactions which stimulate ATP
      hydrolysis by the SopA partition ATPase of plasmid F. By using SopA and SopB
      proteins deficient in DNA binding, we have found that the intrinsic ability of
      SopA to hydrolyze ATP requires direct DNA binding by SopA but not by SopB. Our
      results show that two independent interactions of SopA act in synergy to
      stimulate its ATPase. SopA must interact with (i) DNA, through its ATP-dependent
      nonspecific DNA binding domain and (ii) SopB, which we show here to provide an
      arginine-finger motif. In addition, the latter interaction stimulates ATPase
      maximally when SopB is part of the partition complex. Hence, our data demonstrate
      that DNA acts on SopA in two ways, directly as nonspecific DNA and through SopB
      as centromeric DNA, to fully activate SopA ATP hydrolysis.

PMID- 19740758
TI  - X-ray crystal structure of michaelis complex of aldoxime dehydratase.
AB  - Aldoxime dehydratase (Oxd) catalyzes the dehydration of aldoximes (R-CH=N-OH) to
      their corresponding nitrile (R-C triple bond N). Oxd is a heme-containing enzyme
      that catalyzes the dehydration reaction as its physiological function. We have
      determined the first two structures of Oxd: the substrate-free OxdRE at 1.8 A
      resolution and the n-butyraldoxime- and propionaldoxime-bound OxdREs at 1.8 and
      1.6 A resolutions, respectively. Unlike other heme enzymes, the organic substrate
      is directly bound to the heme iron in OxdRE. We determined the structure of the
      Michaelis complex of OxdRE by using the unique substrate binding and activity
      regulation properties of Oxd. The Michaelis complex was prepared by x-ray
      cryoradiolytic reduction of the ferric dead-end complex in which Oxd contains a
      Fe(3+) heme form. The crystal structures reveal the mechanism of substrate
      recognition and the catalysis of OxdRE.

PMID- 19740759
TI  - Peroxidase activity of hemoglobin-haptoglobin complexes: covalent aggregation and
      oxidative stress in plasma and macrophages.
AB  - As a hemoprotein, hemoglobin (Hb) can, in the presence of H(2)O(2), act as a
      peroxidase. In red blood cells, this activity is regulated by the reducing
      environment. For stroma-free Hb this regulation is lost, and the potential for Hb
      to become a peroxidase is high and further increased by inflammatory cells
      generating superoxide. The latter can be converted into H(2)O(2) and feed Hb
      peroxidase activity. Haptoglobins (Hp) bind with extracellular Hb and reportedly
      weaken Hb peroxidase activity. Here we demonstrate that: (i) Hb peroxidase
      activity is retained upon binding with Hp; (ii) in the presence of H(2)O(2), Hb
      Hp peroxidase complexes undergo covalent cross-linking; (iii) peroxidase activity
      of Hb-Hp complexes and aggregates consumes reductants such as ascorbate and
      nitric oxide; (iv) cross-linked Hb-Hp aggregates are taken up by macrophages at
      rates exceeding those for noncovalently cross-linked Hb-Hp complexes; (v) the
      engulfed Hb-Hp aggregates activate superoxide production and induce intracellular
      oxidative stress (deplete endogenous glutathione and stimulate lipid
      peroxidation); (vi) Hb-Hp aggregates cause cytotoxicity to macrophages; and (vii)
      Hb-Hp aggregates are present in septic plasma. Overall, our data suggest that
      under conditions of severe inflammation and oxidative stress, peroxidase activity
      of Hb-Hp covalent aggregates may cause macrophage dysfunction and microvascular
      vasoconstriction, which are commonly seen in severe sepsis and hemolytic
      diseases.

PMID- 19740760
TI  - Cohort profile: the PROLIFE study in Kerala, India.

PMID- 19740761
TI  - An analytical platform for mass spectrometry-based identification and chemical
      analysis of RNA in ribonucleoprotein complexes.
AB  - We describe here a mass spectrometry (MS)-based analytical platform of RNA, which
      combines direct nano-flow reversed-phase liquid chromatography (RPLC) on a spray
      tip column and a high-resolution LTQ-Orbitrap mass spectrometer. Operating RPLC
      under a very low flow rate with volatile solvents and MS in the negative mode, we
      could estimate highly accurate mass values sufficient to predict the nucleotide
      composition of a approximately 21-nucleotide small interfering RNA, detect post
      transcriptional modifications in yeast tRNA, and perform collision-induced
      dissociation/tandem MS-based structural analysis of nucleolytic fragments of RNA
      at a sub-femtomole level. Importantly, the method allowed the identification and
      chemical analysis of small RNAs in ribonucleoprotein (RNP) complex, such as the
      pre-spliceosomal RNP complex, which was pulled down from cultured cells with a
      tagged protein cofactor as bait. We have recently developed a unique genome
      oriented database search engine, Ariadne, which allows tandem MS-based
      identification of RNAs in biological samples. Thus, the method presented here has
      broad potential for automated analysis of RNA; it complements conventional
      molecular biology-based techniques and is particularly suited for simultaneous
      analysis of the composition, structure, interaction, and dynamics of RNA and
      protein components in various cellular RNP complexes.

PMID- 19740762
TI  - In vivo methylation of mtDNA reveals the dynamics of protein-mtDNA interactions.
AB  - To characterize the organization of mtDNA-protein complexes (known as nucleoids)
      in vivo, we have probed the mtDNA surface exposure using site-specific DNA
      methyltransferases targeted to the mitochondria. We have observed that DNA
      methyltransferases have different accessibility to different sites on the mtDNA
      based on the levels of protein occupancy. We focused our studies on selected
      regions of mtDNA that are believed to be major regulatory regions involved in
      transcription and replication. The transcription termination region (TERM) within
      the tRNA(Leu(UUR)) gene was consistently and strongly protected from methylation,
      suggesting frequent and high affinity binding of mitochondrial transcription
      termination factor 1 (mTERF1) to the site. Protection from methylation was also
      observed in other regions of the mtDNA, including the light and heavy strand
      promoters (LSP, HSP) and the origin of replication of the light strand (OL).
      Manipulations aiming at increasing or decreasing the levels of the mitochondrial
      transcription factor A (TFAM) led to decreased in vivo methylation, whereas
      manipulations that stimulated mtDNA replication led to increased methylation. We
      also analyzed the effect of ATAD3 and oxidative stress in mtDNA exposure. Our
      data provide a map of human mtDNA accessibility and demonstrate that nucleoids
      are dynamically associated with proteins.

PMID- 19740763
TI  - Characterization of RNA aptamers that disrupt the RUNX1-CBFbeta/DNA complex.
AB  - The transcription factor RUNX1 (AML1) is an important regulator of
      haematopoiesis, and an important fusion partner in leukaemic translocations. High
      affinity DNA binding by RUNX1 requires the interaction of the RUNX1 Runt-Homology
      Domain (RHD) with the core-binding factor beta protein (CBFbeta). To generate
      novel reagents for in vitro and in vivo studies of RUNX1 function, we have
      selected high-affinity RNA aptamers against a recombinant RHD-CBFbeta complex.
      Selection yielded two sequence families, each dominated by a single consensus
      sequence. Aptamers from each family disrupt DNA binding by the RUNX1 protein in
      vitro and compete with sequence-specific dsDNA binding. Minimal, high-affinity (
      approximately 100-160 nM) active aptamer fragments 28 and 30 nts in length,
      consisting of simple short stem-loop structures, were then identified. These bind
      to the RHD subunit and disrupt its interaction with CBFbeta, which is consistent
      with reduced DNA affinity in the presence of aptamer. These aptamers represent
      new reagents that target a novel surface on the RHD required to stabilize the
      recombinant RHD-CBFbeta complex and thus will further aid exploring the functions
      of this key transcription factor.

PMID- 19740764
TI  - Regulation of transcription termination in the nematode Caenorhabditis elegans.
AB  - The current predicted mechanisms that describe RNA polymerase II (pol II)
      transcription termination downstream of protein expressing genes fail to
      adequately explain, how premature termination is prevented in eukaryotes that
      possess operon-like structures. Here we address this issue by analysing
      transcription termination at the end of single protein expressing genes and genes
      located within operons in the nematode Caenorhabditis elegans. By using a
      combination of RT-PCR and ChIP analysis we found that pol II generally
      transcribes up to 1 kb past the poly(A) sites into the 3' flanking regions of the
      nematode genes before it terminates. We also show that pol II does not terminate
      after transcription of internal poly(A) sites in operons. We provide experimental
      evidence that five randomly chosen C. elegans operons are transcribed as
      polycistronic pre-mRNAs. Furthermore, we show that cis-splicing of the first
      intron located in downstream positioned genes in these polycistronic pre-mRNAs is
      critical for their expression and may play a role in preventing premature pol II
      transcription termination.

PMID- 19740765
TI  - Predictable suppression of gene expression by 5'-UTR-based RNA quadruplexes.
AB  - Four-stranded DNA and RNA quadruplexes or G4 motifs are non-B DNA conformations
      that are presumed to form in vivo, although only few explicit evidence has been
      reported. Using bioinformatics the presence of putative DNA G-quadruplexes within
      critical promoter regions has been demonstrated and a regulatory role in
      transcription has been suspected. However, in genomic DNA the presence of the
      complementary strand interferes with the potential to form a quadruplex motif.
      Contrarily RNA G4 motifs have no such limitation and consequently strong
      interference with gene expression is suspected. Nevertheless, experimental
      evidence is scarce. Here we show a well-defined structure-function relationship
      of synthetic quadruplex sequences in 5'-UTRs in multiple mammalian cell-lines. We
      establish a universal 'translational suppressor' effect of these motifs on gene
      expression at the translational level and show for the first time that specific
      features such as loop-length and the number of 'GGG'-repeats further determine
      the suppressive impact. Moreover, a consistent and predictable repression of gene
      expression is observed for naturally occurring RNA G4 motifs, augmenting the
      functional relevance of these unusual nucleic acid structures.

PMID- 19740766
TI  - High-resolution profiling of homing endonuclease binding and catalytic
      specificity using yeast surface display.
AB  - Experimental analysis and manipulation of protein-DNA interactions pose unique
      biophysical challenges arising from the structural and chemical homogeneity of
      DNA polymers. We report the use of yeast surface display for analytical and
      selection-based applications for the interaction between a LAGLIDADG homing
      endonuclease and its DNA target. Quantitative flow cytometry using
      oligonucleotide substrates facilitated a complete profiling of specificity, both
      for DNA-binding and catalysis, with single base pair resolution. These analyses
      revealed a comprehensive segregation of binding specificity and affinity to one
      half of the pseudo-dimeric interaction, while the entire interface contributed
      specificity at the level of catalysis. A single round of targeted mutagenesis
      with tandem affinity and catalytic selection steps provided mechanistic insights
      to the origins of binding and catalytic specificity. These methods represent a
      dynamic new approach for interrogating specificity in protein-DNA interactions.

PMID- 19740767
TI  - Evidence for large diversity in the human transcriptome created by Alu RNA
      editing.
AB  - Adenosine-to-inosine (A-to-I) RNA editing alters the original genomic content of
      the human transcriptome and is essential for maintenance of normal life in
      mammals. A-to-I editing in Alu repeats is abundant in the human genome, with many
      thousands of expressed Alu sequences undergoing editing. Little is known so far
      about the contribution of Alu editing to transcriptome complexity. Transcripts
      derived from a single edited Alu sequence can be edited in multiple sites, and
      thus could theoretically generate a large number of different transcripts. Here
      we explored whether the combinatorial potential nature of edited Alu sequences is
      actually fulfilled in the human transcriptome. We analyzed datasets of editing
      sites and performed an analysis of a detailed transcript set of one edited Alu
      sequence. We found that editing appears at many more sites than detected by
      earlier genomic screens. To a large extent, editing of different sites within the
      same transcript is only weakly correlated. Thus, rather than finding a few
      versions of each transcript, a large number of edited variants arise, resulting
      in immense transcript diversity that eclipses alternative splicing as mechanism
      of transcriptome diversity, although with less impact on the proteome.

PMID- 19740768
TI  - Recognition and coupling of A-to-I edited sites are determined by the tertiary
      structure of the RNA.
AB  - Adenosine-to-inosine (A-to-I) editing has been shown to be an important mechanism
      that increases protein diversity in the brain of organisms from human to fly. The
      family of ADAR enzymes converts some adenosines of RNA duplexes to inosines
      through hydrolytic deamination. The adenosine recognition mechanism is still
      largely unknown. Here, to investigate it, we analyzed a set of selectively edited
      substrates with a cluster of edited sites. We used a large set of individual
      transcripts sequenced by the 454 sequencing technique. On average, we analyzed
      570 single transcripts per edited region at four different developmental stages
      from embryogenesis to adulthood. To our knowledge, this is the first time, large
      scale sequencing has been used to determine synchronous editing events. We
      demonstrate that edited sites are only coupled within specific distances from
      each other. Furthermore, our results show that the coupled sites of editing are
      positioned on the same side of a helix, indicating that the three-dimensional
      structure is key in ADAR enzyme substrate recognition. Finally, we propose that
      editing by the ADAR enzymes is initiated by their attraction to one principal
      site in the substrate.

PMID- 19740769
TI  - Time-resolved fluorescence studies of nucleotide flipping by restriction enzymes.
AB  - Restriction enzymes Ecl18kI, PspGI and EcoRII-C, specific for interrupted 5-bp
      target sequences, flip the central base pair of these sequences into their
      protein pockets to facilitate sequence recognition and adjust the DNA cleavage
      pattern. We have used time-resolved fluorescence spectroscopy of 2-aminopurine
      labelled DNA in complex with each of these enzymes in solution to explore the
      nucleotide flipping mechanism and to obtain a detailed picture of the molecular
      environment of the extrahelical bases. We also report the first study of the 7-bp
      cutter, PfoI, whose recognition sequence (T/CCNGGA) overlaps with that of the
      Ecl18kI-type enzymes, and for which the crystal structure is unknown. The time
      resolved fluorescence experiments reveal that PfoI also uses base flipping as
      part of its DNA recognition mechanism and that the extrahelical bases are
      captured by PfoI in binding pockets whose structures are quite different to those
      of the structurally characterized enzymes Ecl18kI, PspGI and EcoRII-C. The
      fluorescence decay parameters of all the enzyme-DNA complexes are interpreted to
      provide insight into the mechanisms used by these four restriction enzymes to
      flip and recognize bases and the relationship between nucleotide flipping and DNA
      cleavage.

PMID- 19740770
TI  - HMMCONVERTER 1.0: a toolbox for hidden Markov models.
AB  - Hidden Markov models (HMMs) and their variants are widely used in Bioinformatics
      applications that analyze and compare biological sequences. Designing a novel
      application requires the insight of a human expert to define the model's
      architecture. The implementation of prediction algorithms and algorithms to train
      the model's parameters, however, can be a time-consuming and error-prone task. We
      here present HMMConverter, a software package for setting up probabilistic HMMs,
      pair-HMMs as well as generalized HMMs and pair-HMMs. The user defines the model
      itself and the algorithms to be used via an XML file which is then directly
      translated into efficient C++ code. The software package provides linear-memory
      prediction algorithms, such as the Hirschberg algorithm, banding and the
      integration of prior probabilities and is the first to present computationally
      efficient linear-memory algorithms for automatic parameter training. Users of
      HMMConverter can thus set up complex applications with a minimum of effort and
      also perform parameter training and data analyses for large data sets.

PMID- 19740771
TI  - GSK3beta is a negative regulator of the transcriptional coactivator MAML1.
AB  - Glycogen synthase kinase 3beta (GSK3beta) is involved in several cellular
      signaling systems through regulation of the activity of diverse transcription
      factors such as Notch, p53 and beta-catenin. Mastermind-like 1 (MAML1) was
      originally identified as a Notch coactivator, but has also been reported to
      function as a transcriptional coregulator of p53, beta-catenin and MEF2C. In this
      report, we show that active GSK3beta directly interacts with the MAML1 N-terminus
      and decreases MAML1 transcriptional activity, suggesting that GSK3beta might
      target a coactivator in its regulation of gene expression. We have previously
      shown that MAML1 increases global acetylation of histones, and here we show that
      the GSK3 inhibitor SB41, further enhances MAML1-dependent histone acetylation in
      cells. Finally, MAML1 translocates GSK3beta to nuclear bodies; this function
      requires full-length MAML1 protein.

PMID- 19740773
TI  - Selective site right ventricular pacing.
AB  - The right ventricular apex (RVA) has been the elective site for placing
      endocardial pacing leads since 1959 when Furman described the use of the
      transvenous route for pacemaker implantation. This site was used because it is
      easily accessible, readily identified and associated with a stable position and
      reliable chronic pacing parameters. It was recognised, however, that pacing from
      the RVA did not reproduce normal ventricular conduction or contraction. With the
      advent of reliable active fixation leads, alternative right ventricular sites
      became accessible and began to be explored. In this review, the detrimental
      effects of RVA pacing are outlined, the right ventricular outflow tract is
      defined and the evidence for selective site pacing is discussed.

PMID- 19740772
TI  - The loss of histone H3 lysine 9 acetylation due to dSAGA-specific dAda2b mutation
      influences the expression of only a small subset of genes.
AB  - In Drosophila, the dADA2b-containing dSAGA complex is involved in histone H3
      lysine 9 and 14 acetylation. Curiously, although the lysine 9- and 14-acetylated
      histone H3 levels are drastically reduced in dAda2b mutants, these animals
      survive until a late developmental stage. To study the molecular consequences of
      the loss of histone H3 lysine 9 and 14 acetylation, we compared the total
      messenger ribonucleic acid (mRNA) profiles of wild type and dAda2b mutant animals
      at two developmental stages. Global gene expression profiling indicates that the
      loss of dSAGA-specific H3 lysine 9 and 14 acetylation results in the expression
      change (up- or down-regulation) of a rather small subset of genes and does not
      cause a general transcription de-regulation. Among the genes up-regulated in
      dAda2b mutants, particularly high numbers are those which play roles in
      antimicrobial defense mechanisms. Results of chromatin immunoprecipitation
      experiments indicate that in dAda2b mutants, the lysine 9-acetylated histone H3
      levels are decreased both at dSAGA up- and down-regulated genes. In contrast to
      that, in the promoters of dSAGA-independent ribosomal protein genes a high level
      of histone H3K9ac is maintained in dAda2b mutants. Our data suggest that by
      acetylating H3 at lysine 9, dSAGA modifies Pol II accessibility to specific
      promoters differently.

PMID- 19740774
TI  - Rationale for continuous chest compression cardiopulmonary resuscitation.
AB  - Every year more than a million cardiac arrests are documented in the
      industrialised nations of the world, with the majority occurring in settings
      outside hospital. A major factor in survival after out-of-hospital cardiac arrest
      (OHCA) is early institution of bystander resuscitation efforts. Sadly, the
      majority of OHCAs do not receive bystander resuscitation for a variety of
      reasons. One of them is the requirement for mouth-to-mouth (MTM) ventilation. The
      2008 American Heart Association recommendation for "hands only" or continuous
      chest compression cardiopulmonary resuscitation (CPR) for untrained lay people
      was a welcome change. However, evidence indicates that MTM and other forms of
      positive pressure ventilation should be eliminated for all bystanders responding
      to primary cardiac arrest (unexpected witnessed collapse in an unresponsive
      person). The requirement for MTM ventilation may well be indicated for patients
      with respiratory arrest but is detrimental during early resuscitation efforts by
      anyone providing CPR to patients with primary cardiac arrest. This article
      provides rationale for continuous chest compression CPR by all bystanders.

PMID- 19740775
TI  - Differential regulation of interleukin 17 and interferon gamma production in
      inflammatory bowel disease.
AB  - BACKGROUND AND AIMS: Interleukin 17 (IL17) is now known to be involved in a
      number of chronic inflammatory disorders. However, the mechanisms regulating its
      production in inflammatory bowel disease (IBD) are still unclear. METHODS:
      Endoscopic biopsies or surgical specimens were taken from inflamed and uninflamed
      colonic mucosa of 72 patients with IBD (38 with Crohn's disease and 34 with
      ulcerative colitis), and normal colon of 38 control subjects. IL17 and interferon
      gamma (IFNgamma) were detected by ELISA in the supernatants of biopsies cultured
      ex vivo, and anti-CD3/CD28-stimulated lamina propria mononuclear cells (LPMCs)
      incubated with IL12, IL23, IL1beta plus IL6, transforming growth factor beta1
      (TGFbeta1), or anti-IL21 neutralising antibody. Intracellular flow cytometry was
      performed to analyse mucosal Th17 and Th1/Th17 cells. RESULTS: IL17 production by
      organ culture biopsies was higher in IBD inflamed mucosa than IBD uninflamed
      mucosa and controls, and was equivalent in amount to IFNgamma. Anti-CD3/CD28
      stimulated IBD LPMCs produced higher IL17 amounts compared to controls. The
      percentages of Th17 and Th1/Th17 cells were increased in patients with IBD. IL23
      and IL1beta plus IL6 had no effect on IBD LPMC production of IL17; however, IL12
      markedly increased IFNgamma production and decreased IL17 production. TGFbeta1
      dose-dependently decreased IFNgamma, but had no significant inhibitory effect on
      IL17 production. Blocking IL21 significantly downregulated IL17 production.
      CONCLUSIONS: Our findings support a role for IL12, TGFbeta and IL21 in modulating
      IL17/IFNgamma production in IBD. The abundant IL17 in inflamed IBD mucosa may
      help explain the relative lack of efficacy of anti-IFNgamma antibodies in
      clinical trials of Crohn's disease.

PMID- 19740776
TI  - Socioeconomic determinants for compliance to colorectal cancer screening. A
      multilevel analysis.
AB  - BACKGROUND: Compliance in cancer screening among socially disadvantaged persons
      is known to be lower than among more socially advantaged persons. However, most
      of the studies regarding compliance proceed via a questionnaire and are thus
      limited by self-reported measures of participation and by participation bias.
      This study aimed at investigating the influence of socioeconomic characteristics
      on compliance to an organised colorectal cancer screening programme on an
      unbiased sample based on data from the entire target population within a French
      geographical department, Calvados (n=180 045). METHODS: Individual data of
      participation and aggregate socioeconomic data, from the structure responsible
      for organising screening and the French census, respectively, were analysed
      simultaneously by a multilevel model. RESULTS: Uptake was significantly higher in
      women than in men (OR=1.33; 95% CI 1.21 to 1.45), and significantly lower in the
      youngest (50-59 years) and in the oldest (70-74 years) persons, compared with
      intermediate ages (60-69 years), with OR=0.70 (95% CI 0.63 to 0.77) and OR=0.82
      (95% CI 0.72 to 0.93), respectively. Uptake fell with increasing level of
      deprivation. There was a significant difference of uptake probability between the
      least deprived and the most deprived areas (OR=0.68; 95% CI 0.59 to 0.79). No
      significant influence of the general practitioners density was found. CONCLUSION:
      Multilevel analysis allowed to detect areas of weak uptake linked to areas of
      strong deprivation. These results suggest that targeting populations with a risk
      of low compliance, as identified both socially and geographically in our study,
      could be adopted to minimise inequalities in screening.

PMID- 19740777
TI  - Abstracts of the Society for Social Medicine 53rd Annual Scientific Meeting, 9-11
      September 2009.

PMID- 19740872
TI  - Evaluation of ocular surface disorders: a new diagnostic tool based on impression
      cytology and confocal laser scanning microscopy.
AB  - AIM: To provide a new tool for the evaluation of altered ocular surfaces by using
      a combination of impression cytology, laser scanning confocal microscopy and
      advanced image analysis. METHODS: The expression of keratin 3 (K3), keratin 12
      (K12), keratin 19 (K19) and mucin 1 (MUC1) was analysed by immunofluorescence on
      both histological sections of nine corneoscleral buttons from normal donors
      comprising conjunctiva, limbus and cornea and impression cytology specimens from
      six healthy normal subjects (12 eyes) and 12 patients with chronic ocular surface
      disorders. Levels of fluorescence expression of the different markers were
      quantified through quantitative fluorescence immunohistochemistry (Q-FIHC).
      RESULTS: Impression cytology specimens from normal and diseased ocular surfaces
      showed distinct expression patterns for K12 and MUC1. Healthy corneas expressed
      only K12 (but not MUC1), while conjunctivalised corneas from patients with limbal
      stem cell deficiency (LSCD) were characterised by the presence of MUC1 and the
      disappearance of K12. Similar clear-cut results were not seen with the K3/K19
      markers, which showed lack of specificity and overlapping signals in cornea and
      conjunctiva impression cytology specimens. CONCLUSIONS: The ability of K12 and of
      the antibody against MUC1 to discriminate clearly between limbus/cornea and
      conjunctiva in impression cytology specimens could become a valuable diagnostic
      tool for ophthalmologists in order to evaluate alterations of the ocular surface
      and the grading of LSCD.

PMID- 19740873
TI  - A dynamic population-based model for the development of work-related respiratory
      health effects among bakery workers.
AB  - OBJECTIVES: This paper presents a dynamic population-based model for the
      development of sensitisation and respiratory symptoms in bakery workers. The
      model simulates a population of individual workers longitudinally and tracks the
      development of work-related sensitisation and respiratory symptoms in each
      worker. METHODS: The model has three components: a multi-stage disease model
      describing the development of sensitisation and respiratory symptoms in each
      worker over time; an exposure model describing occupational exposure to flour
      dust and allergens; and a basic population model describing the length of a
      worker's career in the bakery sector and the influx of new workers. Each worker's
      disease state is modelled independently using a discrete time Markov Chain,
      updated yearly using each individual's simulated exposure. A Bayesian analysis of
      data from a recent epidemiological study provided estimates of the yearly
      transition probabilities between disease states. RESULTS: For non-atopic/non
      sensitised workers the estimated probabilities of developing moderate (upper
      respiratory) symptoms and progression to severe (lower respiratory) symptoms are
      0.4% (95% CI 0.3 to 0.5%) and 1.1% (95% CI 0.6 to 1.9%) per mg/m(3)/year of flour
      dust, respectively, and approximately twice these for atopic workers. The model
      predicts that 36% (95% CI 26 to 46%) of workers with severe symptoms are
      sensitised to wheat and 22% (95% CI 12 to 37%) to alpha-amylase. The predicted
      mean latency period for respiratory symptoms was 10.3 years (95% CI 8.3 to 12.3).
      CONCLUSIONS: While the model provides a valuable population-level representation
      of the mechanisms contributing to respiratory diseases in bakers, it was
      primarily developed for use in quantitative health impact assessment. Future
      research will use the model to evaluate a range of workplace interventions,
      including achievable reductions in exposure and health surveillance. The general
      methodology is applicable to other diseases such as chronic obstructive pulmonary
      disease, silicosis and musculoskeletal disorders and could be particularly
      valuable for forecasting changes in long latency diseases.

PMID- 19740874
TI  - Outbreak and persistence of opportunistic symbiotic dinoflagellates during the
      2005 Caribbean mass coral 'bleaching' event.
AB  - Reef corals are sentinels for the adverse effects of rapid global warming on the
      planet's ecosystems. Warming sea surface temperatures have led to frequent
      episodes of bleaching and mortality among corals that depend on endosymbiotic
      micro-algae (Symbiodinium) for their survival. However, our understanding of the
      ecological and evolutionary response of corals to episodes of thermal stress
      remains inadequate. For the first time, we describe how the symbioses of major
      reef-building species in the Caribbean respond to severe thermal stress before,
      during and after a severe bleaching event. Evidence suggests that background
      populations of Symbiodinium trenchi (D1a) increased in prevalence and abundance,
      especially among corals that exhibited high sensitivity to stress. Contrary to
      previous hypotheses, which posit that a change in symbiont occurs subsequent to
      bleaching, S. trenchi increased in the weeks leading up to and during the
      bleaching episode and disproportionately dominated colonies that did not bleach.
      During the bleaching event, approximately 20 per cent of colonies surveyed
      harboured this symbiont at high densities (calculated at less than 1.0% only
      months before bleaching began). However, competitive displacement by homologous
      symbionts significantly reduced S. trenchi's prevalence and dominance among
      colonies after a 2-year period following the bleaching event. While the extended
      duration of thermal stress in 2005 provided an ecological opportunity for a rare
      host-generalist symbiont, it remains unclear to what extent the rise and fall of
      S. trenchi was of ecological benefit or whether its increased prevalence was an
      indicator of weakening coral health.

PMID- 19740875
TI  - Harvest-induced disruptive selection increases variance in fitness-related
      traits.
AB  - The form of Darwinian selection has important ecological and management
      implications. Negative effects of harvesting are often ascribed to size
      truncation (i.e. strictly directional selection against large individuals) and
      resultant decrease in trait variability, which depresses capacity to buffer
      environmental change, hinders evolutionary rebound and ultimately impairs
      population recovery. However, the exact form of harvest-induced selection is
      generally unknown and the effects of harvest on trait variability remain
      unexplored. Here we use unique data from the Windermere (UK) long-term ecological
      experiment to show in a top predator (pike, Esox lucius) that the fishery does
      not induce size truncation but disruptive (diversifying) selection, and does not
      decrease but rather increases variability in pike somatic growth rate and size at
      age. This result is supported by complementary modelling approaches removing the
      effects of catch selectivity, selection prior to the catch and environmental
      variation. Therefore, fishing most likely increased genetic variability for
      somatic growth in pike and presumably favoured an observed rapid evolutionary
      rebound after fishery relaxation. Inference about the mechanisms through which
      harvesting negatively affects population numbers and recovery should
      systematically be based on a measure of the exact form of selection. From a
      management perspective, disruptive harvesting necessitates combining a
      preservation of large individuals with moderate exploitation rates, and thus
      provides a comprehensive tool for sustainable exploitation of natural resources.

PMID- 19740876
TI  - Phase-dependent outbreak dynamics of geometrid moth linked to host plant
      phenology.
AB  - Climatically driven Moran effects have often been invoked as the most likely
      cause of regionally synchronized outbreaks of insect herbivores without
      identifying the exact mechanism. However, the degree of match between host plant
      and larval phenology is crucial for the growth and survival of many spring
      feeding pest insects, suggesting that a phenological match/mismatch-driven Moran
      effect may act as a synchronizing agent. We analyse the phase-dependent spatial
      dynamics of defoliation caused by cyclically outbreaking geometrid moths in
      northern boreal birch forest in Fennoscandia through the most recent massive
      outbreak (2000-2008). We use satellite-derived time series of the prevalence of
      moth defoliation and the onset of the growing season for the entire region to
      investigate the link between the patterns of defoliation and outbreak spread. In
      addition, we examine whether a phase-dependent coherence in the pattern of
      spatial synchrony exists between defoliation and onset of the growing season, in
      order to evaluate if the degree of matching phenology between the moth and their
      host plant could be the mechanism behind a Moran effect. The strength of regional
      spatial synchrony in defoliation and the pattern of defoliation spread were both
      highly phase-dependent. The incipient phase of the outbreak was characterized by
      high regional synchrony in defoliation and long spread distances, compared with
      the epidemic and crash phase. Defoliation spread was best described using a two
      scale stratified spread model, suggesting that defoliation spread is governed by
      two processes operating at different spatial scale. The pattern of phase
      dependent spatial synchrony was coherent in both defoliation and onset of the
      growing season. This suggests that the timing of spring phenology plays a role in
      the large-scale synchronization of birch forest moth outbreaks.

PMID- 19740877
TI  - Phylogenetic trait conservatism and the evolution of functional trade-offs in
      arbuscular mycorrhizal fungi.
AB  - The diversity of functional and life-history traits of organisms depends on
      adaptation as well as the legacy of shared ancestry. Although the evolution of
      traits in macro-organisms is well studied, relatively little is known about
      character evolution in micro-organisms. Here, we surveyed an ancient and
      ecologically important group of microbial plant symbionts, the arbuscular
      mycorrhizal (AM) fungi, and tested hypotheses about the evolution of functional
      and life-history traits. Variation in the extent of root and soil colonization by
      AM fungi is constrained to a few nodes basal to the most diverse groups within
      the phylum, with relatively little variation associated with recent divergences.
      We found no evidence for a trade-off in biomass allocated to root versus soil
      colonization in three published glasshouse experiments; rather these traits were
      positively correlated. Partial support was observed for correlated evolution
      between fungal colonization strategies and functional benefits of the symbiosis
      to host plants. The evolution of increased soil colonization was positively
      correlated with total plant biomass and shoot phosphorus content. Although the
      effect of AM fungi on infection by root pathogens was phylogenetically conserved,
      there was no evidence for correlated evolution between the extent of AM fungal
      root colonization and pathogen infection. Variability in colonization strategies
      evolved early in the diversification of AM fungi, and we propose that these
      strategies were influenced by functional interactions with host plants, resulting
      in an evolutionary stasis resembling trait conservatism.

PMID- 19740878
TI  - Community monopolization: local adaptation enhances priority effects in an
      evolving metacommunity.
AB  - The diversity and composition of biological communities might often depend on
      colonization history because early colonists can exclude future colonists through
      a priority effect. These priority effects, which have been observed across a wide
      variety of ecosystems, often arise because early colonists have sufficient time
      to use available resources efficiently and subsequently withhold them from
      invaders. Here, we explore the extent to which rapid local adaptive evolution
      contributes to the pervasiveness of these priority effects. Using an individual
      based simulation, we show that early colonization allows the descendants of
      colonists to adapt to novel conditions and reduce the establishment success of an
      initially ecologically equivalent competing species. Our model predicts that
      slight differences in colonization timing and adaptive capacity between species
      can substantially alter the dynamics and diversity of communities. We also show
      that priority effects and gene flow can generate a novel mechanism for the
      expansion and retraction of species distributions in a metacommunity. Our results
      suggest that local adaptation combined with stochastic colonization events can
      obscure direct relationships between species distributions and environmental
      gradients. Given the increasing recognition of rapid, microgeographic evolution
      in natural populations, we expect that evolutionary priority effects could affect
      the structure and dynamics of many natural metacommunities.

PMID- 19740879
TI  - Evidence of a myco-heterotroph in the plant family Ericaceae that lacks
      mycorrhizal specificity.
AB  - Myco-heterotrophy is one of the longest-studied aspects of the mycorrhizal
      symbiosis, but there remain many critical, unanswered questions regarding the
      ecology and physiology of myco-heterotrophic plants and their associated fungi.
      The vast majority of all myco-heterotrophs studied to date have exhibited
      specificity towards narrow lineages of fungi, but it is unclear whether the loss
      of photosynthesis in these plants is contingent upon fungal specialization. Here,
      we examine the fungal associates of the myco-heterotroph Pyrola aphylla
      (Ericaceae) and its closest green relative Pyrola picta to determine the pattern
      of mycorrhizal specialization. Our findings show that both plant species
      associate with a range of root-inhabiting fungi, the majority of which are
      ectomycorrhizal taxa. This study provides the first example of a eudicotyledonous
      myco-heterotroph that is a mycorrhizal generalist, indicating that the loss of
      photosynthesis in myco-heterotrophs is not contingent upon fungal specialization.

PMID- 19740880
TI  - Father-offspring phenotypic correlations suggest intralocus sexual conflict for a
      fitness-linked trait in a wild sexually dimorphic mammal.
AB  - In sexually dimorphic and polygynous mammals, sexual selection often favours
      large males with well-developed weaponry, as these secondary sexual characters
      confer advantages in intrasexual competition and are often preferred by females.
      Little is known, however, about the effects of sexually selected paternal traits
      on offspring phenotype in wild mammals, especially when considering that shared
      phenotypic traits and selection can also differ greatly between genders. Here, we
      conducted molecular parentage analyses in a long-term study population of
      mountain goats (Oreamnos americanus), an ungulate exhibiting high sexual
      dimorphism in mass, to first assess the determinants of yearly reproductive
      success (YRS) in males. We then examined the effects of paternal characteristics
      on offspring mass at 1 year of age. Paternity was highly skewed, with 9 per cent
      of 57 males siring 51 per cent of 96 offspring assigned over 12 years. Male YRS
      increased with age until apparent reproductive senescence at 9 years, but mass
      was a stronger determinant of siring success than age, horn length or social
      rank. Mass of sons increased with paternal mass, but the mass of daughters was
      negatively related to that of their father, a finding consistent with recent
      theory on intralocus sexual conflict. Because early differences in mass persisted
      to early adulthood, sex-specific effects of paternal mass can have important
      fitness consequences, as adult mass is positively linked with reproduction in
      both sexes. Divergent father-offspring phenotypic correlations may partly explain
      the maintenance of sexual dimorphism in mountain goats and the large variance
      observed for this homologous trait within each gender in polygynous mammals.

PMID- 19740881
TI  - Human odometer is gait-symmetry specific.
AB  - In 1709, Berkeley hypothesized of the human that distance is measurable by 'the
      motion of his body, which is perceivable by touch'. To be sufficiently general
      and reliable, Berkeley's hypothesis must imply that distance measured by legged
      locomotion approximates actual distance, with the measure invariant to gait,
      speed and number of steps. We studied blindfolded human participants in a task in
      which they travelled by legged locomotion from a fixed starting point A to a
      variable terminus B, and then reproduced, by legged locomotion from B, the A-B
      distance. The outbound ('measure') and return ('report') gait could be the same
      or different, with similar or dissimilar step sizes and step frequencies. In five
      experiments we manipulated bipedal gait according to the primary versus secondary
      distinction revealed in symmetry group analyses of locomotion patterns.
      Berkeley's hypothesis held only when the measure and report gaits were of the
      same symmetry class, indicating that idiothetic distance measurement is gait
      symmetry specific. Results suggest that human odometry (and perhaps animal
      odometry more generally) entails variables that encompass the limbs in
      coordination, such as global phase, and not variables at the level of the single
      limb, such as step length and step number, as traditionally assumed.

PMID- 19740882
TI  - Trophic amplification of climate warming.
AB  - Ecosystems can alternate suddenly between contrasting persistent states due to
      internal processes or external drivers. It is important to understand the
      mechanisms by which these shifts occur, especially in exploited ecosystems. There
      have been several abrupt marine ecosystem shifts attributed either to fishing,
      recent climate change or a combination of these two drivers. We show that
      temperature has been an important driver of the trophodynamics of the North Sea,
      a heavily fished marine ecosystem, for nearly 50 years and that a recent
      pronounced change in temperature established a new ecosystem dynamic regime
      through a series of internal mechanisms. Using an end-to-end ecosystem approach
      that included primary producers, primary, secondary and tertiary consumers, and
      detritivores, we found that temperature modified the relationships among species
      through nonlinearities in the ecosystem involving ecological thresholds and
      trophic amplifications. Trophic amplification provides an alternative mechanism
      to positive feedback to drive an ecosystem towards a new dynamic regime, which in
      this case favours jellyfish in the plankton and decapods and detritivores in the
      benthos. Although overfishing is often held responsible for marine ecosystem
      degeneration, temperature can clearly bring about similar effects. Our results
      are relevant to ecosystem-based fisheries management (EBFM), seen as the way
      forward to manage exploited marine ecosystems.

PMID- 19740883
TI  - Sex allocation predicts mating rate in a simultaneous hermaphrodite.
AB  - Sexual selection theory for separate-sexed animals predicts that the sexes differ
      in the benefit they can obtain from multiple mating. Conventional sex roles
      assume that the relationship between the number of mates and the fitness of an
      individual is steeper in males compared with females. Under these conditions,
      males are expected to be more eager to mate, whereas females are expected to be
      choosier. Here we hypothesize that the sex allocation, i.e. the reproductive
      investment devoted to the male versus female function, can be an important
      predictor of the mating strategy in simultaneous hermaphrodites. We argue that
      within-species variation in sex allocation can cause differences in the
      proportional fitness gain derived through each sex function. Individuals should
      therefore adjust their mating strategy in a way that is more beneficial to the
      sex function that is relatively more pronounced. To test this, we experimentally
      manipulated the sex allocation in a simultaneously hermaphroditic flatworm and
      investigated whether this affects the mating behaviour. The results demonstrate
      that individuals with a more male-biased sex allocation (i.e. relatively large
      testes and small ovaries) are more eager to mate compared with individuals with a
      more female-biased sex allocation (i.e. relatively small testes and large
      ovaries). We argue that this pattern is comparable to conventional gender roles
      in separate-sexed organisms.

PMID- 19740884
TI  - Long-term social bonds promote cooperation in the iterated Prisoner's Dilemma.
AB  - Reciprocal altruism, one of the most probable explanations for cooperation among
      non-kin, has been modelled as a Prisoner's Dilemma. According to this game,
      cooperation could evolve when individuals, who expect to play again, use
      conditional strategies like tit-for-tat or Pavlov. There is evidence that humans
      use such strategies to achieve mutual cooperation, but most controlled
      experiments with non-human animals have failed to find cooperation. One reason
      for this could be that subjects fail to cooperate because they behave as if they
      were to play only once. To assess this hypothesis, we conducted an experiment
      with monogamous zebra finches (Taeniopygia guttata) that were tested in a two
      choice apparatus, with either their social partner or an experimental opponent of
      the opposite sex. We found that zebra finches maintained high levels of
      cooperation in an iterated Prisoner's Dilemma game only when interacting with
      their social partner. Although other mechanisms may have contributed to the
      observed difference between the two treatments, our results support the
      hypothesis that animals do not systematically give in to the short-term
      temptation of cheating when long-term benefits exist. Thus, our findings
      contradict the commonly accepted idea that reciprocal altruism will be rare in
      non-human animals.

PMID- 19740885
TI  - Seasonality and comparative dynamics of six childhood infections in pre
      vaccination Copenhagen.
AB  - Seasonal variation in infection transmission is a key determinant of epidemic
      dynamics of acute infections. For measles, the best-understood strongly
      immunizing directly transmitted childhood infection, the perception is that term
      time forcing is the main driver of seasonality in developed countries. The degree
      to which this holds true across other acute immunizing childhood infections is
      not clear. Here, we identify seasonal transmission patterns using a unique long
      term dataset with weekly incidence of six infections including measles. Data on
      age-incidence allow us to quantify the mean age of infection. Results indicate
      correspondence between dips in transmission and school holidays for some
      infections, but there are puzzling discrepancies, despite close correspondence
      between average age of infection and age of schooling. Theoretical predictions of
      the relationship between amplitude of seasonality and basic reproductive rate of
      infections that should result from term-time forcing are also not upheld. We
      conclude that where yearly trajectories of susceptible numbers are perturbed,
      e.g. via waning of immunity, seasonality is unlikely to be entirely driven by
      term-time forcing. For the three bacterial infections, pertussis, scarlet fever
      and diphtheria, there is additionally a strong increase in transmission during
      the late summer before the end of school vacations.

PMID- 19740886
TI  - Taxonomic scale-dependence of habitat niche partitioning and biotic neighbourhood
      on survival of tropical tree seedlings.
AB  - In order to differentiate between mechanisms of species coexistence, we examined
      the relative importance of local biotic neighbourhood, abiotic habitat factors
      and species differences as factors influencing the survival of 2330 spatially
      mapped tropical tree seedlings of 15 species of Myristicaceae in two separate
      analyses in which individuals were identified first to species and then to genus.
      Using likelihood methods, we selected the most parsimonious candidate models as
      predictors of 3 year seedling survival in both sets of analyses. We found
      evidence for differential effects of abiotic niche and neighbourhood processes on
      individual survival between analyses at the genus and species levels. Niche
      partitioning (defined as an interaction of taxonomic identity and abiotic
      neighbourhood) was significant in analyses at the genus level, but did not
      differentiate among species in models of individual seedling survival. By
      contrast, conspecific and congeneric seedling and adult density were retained in
      the minimum adequate models of seedling survival at species and genus levels,
      respectively. We conclude that abiotic niche effects express differences in
      seedling survival among genera but not among species, and that, within genera,
      community and/or local variation in adult and seedling abundance drives variation
      in seedling survival. These data suggest that different mechanisms of coexistence
      among tropical tree taxa may function at different taxonomic or phylogenetic
      scales. This perspective helps to reconcile perceived differences of importance
      in the various non-mutually exclusive mechanisms of species coexistence in hyper
      diverse tropical forests.

PMID- 19740887
TI  - The origin of a selfish B chromosome triggering paternal sex ratio in the
      parasitoid wasp Trichogramma kaykai.
AB  - This study uses molecular and cytogenetic methods to determine the origin of a B
      chromosome in some males of the wasp Trichogramma kaykai. This so-called paternal
      sex ratio (PSR) chromosome transmits only through sperm and shortly after
      fertilization triggers degeneration of the paternal genome, while keeping itself
      intact. The resulting embryos develop into haploid B-chromosome-carrying males.
      Another PSR chromosome with a very similar mode of action is found in the
      distantly related wasp Nasonia vitripennis and its origin was traced by
      transposon similarity to the genus Trichomalopsis, which is closely related to
      Nasonia. To determine whether both PSR chromosomes have a similar origin we aimed
      to reveal the origin of the Trichogramma PSR chromosome. Using fluorescent in
      situ hybridization, we discovered a major satellite repeat on the PSR chromosome,
      the 45S ribosomal DNA. Analysis of the internal transcribed spacer 2 (ITS2) of
      this repeat showed the presence of multiple ITS2 sequences on the PSR chromosome
      resembling either the ITS2 of T. oleae or of T. kaykai. We therefore conclude
      that the Trichogramma PSR chromosome originates from T. oleae or a T. oleae-like
      species. Our results are consistent with different origins for the PSR
      chromosomes in Trichogramma and Nasonia.

PMID- 19740888
TI  - Computer animations stimulate contagious yawning in chimpanzees.
AB  - People empathize with fictional displays of behaviour, including those of
      cartoons and computer animations, even though the stimuli are obviously
      artificial. However, the extent to which other animals also may respond
      empathetically to animations has yet to be determined. Animations provide a
      potentially useful tool for exploring non-human behaviour, cognition and empathy
      because computer-generated stimuli offer complete control over variables and the
      ability to program stimuli that could not be captured on video. Establishing
      computer animations as a viable tool requires that non-human subjects identify
      with and respond to animations in a way similar to the way they do to images of
      actual conspecifics. Contagious yawning has been linked to empathy and poses a
      good test of involuntary identification and motor mimicry. We presented 24
      chimpanzees with three-dimensional computer-animated chimpanzees yawning or
      displaying control mouth movements. The apes yawned significantly more in
      response to the yawn animations than to the controls, implying identification
      with the animations. These results support the phenomenon of contagious yawning
      in chimpanzees and suggest an empathic response to animations. Understanding how
      chimpanzees connect with animations, to both empathize and imitate, may help us
      to understand how humans do the same.

PMID- 19740889
TI  - Anthropoid versus strepsirhine status of the African Eocene primates
      Algeripithecus and Azibius: craniodental evidence.
AB  - Recent fossil discoveries have demonstrated that Africa and Asia were epicentres
      for the origin and/or early diversification of the major living primate lineages,
      including both anthropoids (monkeys, apes and humans) and crown strepsirhine
      primates (lemurs, lorises and galagos). Competing hypotheses favouring either an
      African or Asian origin for anthropoids rank among the most hotly contested
      issues in paleoprimatology. The Afrocentric model for anthropoid origins rests
      heavily on the >45 Myr old fossil Algeripithecus minutus from Algeria, which is
      widely acknowledged to be one of the oldest known anthropoids. However, the
      phylogenetic position of Algeripithecus with respect to other primates has been
      tenuous because of the highly fragmentary fossils that have documented this
      primate until now. Recently recovered and more nearly complete fossils of
      Algeripithecus and contemporaneous relatives reveal that they are not
      anthropoids. New data support the idea that Algeripithecus and its sister genus
      Azibius are the earliest offshoots of an Afro-Arabian strepsirhine clade that
      embraces extant toothcombed primates and their fossil relatives. Azibius exhibits
      anatomical evidence for nocturnality. Algeripithecus has a long, thin and
      forwardly inclined lower canine alveolus, a feature that is entirely compatible
      with the long and procumbent lower canine included in the toothcomb of crown
      strepsirhines. These results strengthen an ancient African origin for crown
      strepsirhines and, in turn, strongly challenge the role of Africa as the
      ancestral homeland for anthropoids.

PMID- 19740890
TI  - Reduced opsin gene expression in a cave-dwelling fish.
AB  - Regressive evolution of structures associated with vision in cave-dwelling
      organisms is the focus of intense research. Most work has focused on differences
      between extreme visual phenotypes: sighted, surface animals and their completely
      blind, cave-dwelling counterparts. We suggest that troglodytic systems,
      comprising multiple populations that vary along a gradient of visual function,
      may prove critical in understanding the mechanisms underlying initial regression
      in visual pathways. Gene expression assays of natural and laboratory-reared
      populations of the Atlantic molly (Poecilia mexicana) revealed reduced opsin
      expression in cave-dwelling populations compared with surface-dwelling
      conspecifics. Our results suggest that the reduction in opsin expression in cave
      dwelling populations is not phenotypically plastic but reflects a hardwired
      system not rescued by exposure to light during retinal ontogeny. Changes in opsin
      gene expression may consequently represent a first evolutionary step in the
      regression of eyes in cave organisms.

PMID- 19740891
TI  - Flip, flop and fly: modulated motor control and highly variable movement patterns
      of autotomized gecko tails.
AB  - Many animals lose and regenerate appendages, and tail autotomy in lizards is an
      extremely well-studied example of this. Whereas the energetic, ecological and
      functional ramifications of tail loss for many lizards have been extensively
      documented, little is known about the behaviour and neuromuscular control of the
      autotomized tail. We used electromyography and high-speed video to quantify the
      motor control and movement patterns of autotomized tails of leopard geckos
      (Eublepharis macularius). In addition to rhythmic swinging, we show that they
      exhibit extremely complex movement patterns for up to 30 min following autotomy,
      including acrobatic flips up to 3 cm in height. Unlike the output of most central
      pattern generators (CPGs), muscular control of the tail is variable and can be
      arrhythmic. We suggest that the gecko tail is well suited for studies involving
      CPGs, given that this spinal preparation is naturally occurring, requires no
      surgery and exhibits complex modulation.

PMID- 19740892
TI  - Great tits search for, capture, kill and eat hibernating bats.
AB  - Ecological pressure paired with opportunism can lead to surprising innovations in
      animal behaviour. Here, we report predation of great tits (Parus major) on
      hibernating pipistrelle bats (Pipistrellus pipistrellus) at a Hungarian cave.
      Over two winters, we directly observed 18 predation events. The tits specifically
      and systematically searched for and killed bats for food. A substantial decrease
      in predation on bats after experimental provisioning of food to the tits further
      supports the hypothesis that bat-killing serves a foraging purpose in times of
      food scarcity. We finally conducted a playback experiment to test whether tits
      would eavesdrop on calls of awakening bats to find them in rock crevices. The
      tits could clearly hear the calls and were attracted to the loudspeaker. Records
      for tit predation on bats at this cave now span more than ten years and thus
      raise the question of whether cultural transmission plays a role for the spread
      of this foraging innovation.

PMID- 19740893
TI  - Sustainable exploitation of temperate fish stocks.
AB  - The theory of maximum sustainable yield (MSY) underpins many fishery management
      regimes and is applied principally as a single species concept. Using a simple
      dynamic biomass production model we show that MSY can be identified from a long
      time series of multi-stock data at a regional scale in the presence of species
      interactions and environmental change. It suggests that MSY is robust and
      calculable in a multispecies environment, offering a realistic reference point
      for fishery management. Furthermore, the demonstration of the existence of MSY
      shows that it is more than a purely theoretical concept. There has been an
      improvement in the status of stocks in the Northeast Atlantic, but our analysis
      suggests further reductions in fishing effort would improve long-term yields.

PMID- 19740894
TI  - Extrapolating non-target risk of Bt crops from laboratory to field.
AB  - The tiered approach to assessing ecological risk of insect-resistant transgenic
      crops assumes that lower tier laboratory studies, which expose surrogate non
      target organisms to high doses of insecticidal proteins, can detect harmful
      effects that might be manifested in the field. To test this assumption, we
      performed meta-analyses comparing results for non-target invertebrates exposed to
      Bacillus thuringiensis (Bt) Cry proteins in laboratory studies with results
      derived from independent field studies examining effects on the abundance of non
      target invertebrates. For Lepidopteran-active Cry proteins, laboratory studies
      correctly predicted the reduced field abundance of non-target Lepidoptera.
      However, laboratory studies incorporating tri-trophic interactions of Bt plants,
      herbivores and parasitoids were better correlated with the decreased field
      abundance of parasitoids than were direct-exposure assays. For predators,
      laboratory tri-trophic studies predicted reduced abundances that were not
      realized in field studies and thus overestimated ecological risk. Exposure to
      Coleopteran-active Cry proteins did not significantly reduce the laboratory
      survival or field abundance of any functional group examined. Our findings
      support the assumption that laboratory studies of transgenic insecticidal crops
      show effects that are either consistent with, or more conservative than, those
      found in field studies, with the important caveat that laboratory studies should
      explore all ecologically relevant routes of exposure.

PMID- 19740895
TI  - A foraging advantage for dichromatic marmosets (Callithrix geoffroyi) at low
      light intensity.
AB  - Most New World monkey species have both dichromatic and trichromatic individuals
      present in the same population. The selective forces acting to maintain the
      variation are hotly debated and are relevant to the evolution of the 'routine'
      trichromatic colour vision found in catarrhine primates. While trichromats have a
      foraging advantage for red food compared with dichromats, visual tasks which
      dichromats perform better have received less attention. Here we examine the
      effects of light intensity on foraging success among marmosets. We find that
      dichromats outperform trichomats when foraging in shade, but not in sun. The
      simplest explanation is that dichromats pay more attention to achromatic cues
      than trichromats. However, dichromats did not show a preference for foraging in
      shade compared with trichromats. Our results reveal several interesting parallels
      with a recent study in capuchin monkeys (Cebus capucinus), and suggest that
      dichromat advantage for certain tasks contributes to maintenance of the colour
      vision polymorphism.

PMID- 19740896
TI  - Does organic farming benefit farmland birds in winter?
AB  - The generally higher biodiversity on organic farms may be influenced by
      management features such as no synthetic pesticide and fertilizer inputs and/or
      by differences in uncropped habitat at the site and landscape scale. We analysed
      bird and habitat data collected on 48 paired organic and conventional farms over
      two winters to determine the extent to which broad-scale habitat differences
      between systems could explain overall differences in farmland bird abundance.
      Density was significantly higher on organic farms for six out of 16 species, and
      none on conventional. Total abundance of all species combined was higher on
      organic farms in both years. Analyses using an information-theoretic approach
      suggested that both habitat extent and farm type were important predictors only
      for starling and greenfinch. Organic farming as currently practised may not
      provide significant benefits to those bird species that are limited by winter
      food resources, in particular, several declining granivores.

PMID- 19740897
TI  - Increased risk of preterm births among women with uterine leiomyoma: a nationwide
      population-based study.
AB  - BACKGROUND: Using a 3-year nationwide population-based database, this study
      examines the risk of adverse pregnancy outcomes [lower birthweight, preterm
      gestation and babies small for gestational age (SGA)] in pregnant women with
      uterine leiomyoma. METHODS: This study linked two data sets: Taiwan's birth
      certificate registry and its National Health Insurance Research Data set. A total
      of 5627 mothers with uterine leiomyoma and 28 135 unaffected mothers were
      included for analysis. After adjusting for mother and infant characteristics and
      monthly family income, log-binominal regression and multivariate regression
      analyses were conducted to examine the risks of preterm birth, SGA and lower
      birthweight among mothers with uterine leiomyoma and unaffected mothers. RESULTS:
      Women with uterine leiomyoma had a significantly higher percentage of preterm
      births (10.98 versus 7.78%, P < 0.001) and SGA infants (19.00 versus 17.28%, P =
      0.002) than unaffected mothers. The mean birthweights for mothers with and
      without uterine leiomyoma were 3083 and 3172 g, respectively (P < 0.001). Log
      binominal regression models show that the adjusted risk ratios of preterm births
      and SGA infants for mothers with uterine leiomyoma were 1.32 (95% CI 1.19-1.46)
      and 1.16 (95% CI 1.08-1.26), respectively, compared with unaffected mothers.
      After finally adjusting for gestational age and other covariates, a multivariate
      regression analysis revealed that women with uterine leiomyoma had, on average, a
      14.7 g lower birthweight than unaffected mothers (P = 0.022). CONCLUSIONS: We
      concluded that after adjusting for potential confounders, women with uterine
      leiomyoma experience a small yet significant increased risk of preterm and SGA
      infants. We suggest that clinicians intensively monitor women with uterine
      leiomyoma during pregnancy.

PMID- 19740898
TI  - Perioperative cooling to prevent adhesion formation may be counterproductive for
      the clinical outcome.

PMID- 19740900
TI  - Cost effectiveness of two therapeutic regimens of infliximab in ankylosing
      spondylitis: economic evaluation within a randomised controlled trial.
AB  - OBJECTIVE: To determine the incremental cost-effectiveness ratios (ICERs) of two
      therapeutic regimens of infliximab for ankylosing spondylitis (AS). METHODS: 230
      patients with active AS who were participating in a randomised controlled trial
      comparing two infliximab infusion modalities-every 6 weeks (Q6) and on demand
      (DEM)-were included in an economic evaluation within the trial. Data were
      collected by phone every 3 months for 1 year. Direct and indirect costs were
      calculated from a payer perspective. Health-related quality of life was assessed
      with a general health rating scale. ICERs were calculated for one 20% improvement
      (ASAS20), for one partial remission and for one quality-adjusted life year (QALY)
      gained. RESULTS: The Q6 regimen was significantly more efficacious than the DEM
      regimen but also more costly (euro22 388 vs euro17 596; p<0.001), because it
      required significantly more infliximab infusions per patient (8.4 vs 6.2). The
      ICERs of the Q6 to DEM regimen were euro15 841 for one ASAS20 response, euro23
      296 for one partial remission and euro50 760 for one QALY gained. CONCLUSION: The
      administration of infliximab every 6 weeks is cost effective as compared with a
      DEM regimen; however, the ICER is close to the acceptability threshold of euro50
      000 for one QALY gained. TRIAL REGISTRATION NUMBER: NCT 00439283.

PMID- 19740899
TI  - Early prenatal androgenization results in diminished ovarian reserve in adult
      female rhesus monkeys.
AB  - BACKGROUND: Early prenatal androgenization (PA) accelerates follicle
      differentiation and impairs embryogenesis in adult female rhesus monkeys (Macaca
      mulatta) undergoing FSH therapy for IVF. To determine whether androgen excess in
      utero affects follicle development over time, this study examines whether PA
      exposure, beginning at gestational days 40-44 (early treated) or 100-115 (late
      treated), alters the decline in serum anti-Mullerian hormone (AMH) levels with
      age in adult female rhesus monkeys and perturbs their ovarian response to
      recombinant human FSH (rhFSH) therapy for IVF. METHODS: Thirteen normal
      (control), 11 early-treated and 6 late-treated PA adult female monkeys had serum
      AMH levels measured at random times of the menstrual cycle or anovulatory period.
      Using some of the same animals, basal serum AMH, gonadotrophins and steroids were
      also measured in six normal, five early-treated and three late-treated PA female
      monkeys undergoing FSH therapy for IVF during late-reproductive life (>17 years);
      serum AMH also was measured on day of HCG administration and at oocyte retrieval.
      RESULTS: Serum AMH levels in early-treated PA females declined with age to levels
      that were significantly lower than those of normal (P < or = 0.05) and late
      treated PA females (P < or = 0.025) by late-reproductive life. Serum AMH levels
      positively predicted numbers of total/mature oocytes retrieved, with early
      treated PA females having the lowest serum AMH levels, fewest oocytes retrieved
      and lowest percentage of females with fertilized oocytes that cleaved.
      CONCLUSIONS: Based on these animals, early PA appears to program an exaggerated
      decline in ovarian reserve with age, suggesting that epigenetically induced
      hormonal factors during fetal development may influence the cohort size of
      ovarian follicles after birth.

PMID- 19740901
TI  - Successful use of rituximab in a patient with Churg-Strauss syndrome and
      refractory central nervous system involvement.

PMID- 19740902
TI  - Replication of association between FAM167A(C8orf13)-BLK region and rheumatoid
      arthritis in a Japanese population.

PMID- 19740903
TI  - Hormonal replacement therapy may reduce the risk for RA in women with early
      arthritis who carry HLA-DRB1 *01 and/or *04 alleles by protecting against the
      production of anti-CCP: results from the ESPOIR cohort.
AB  - OBJECTIVE: To assess the effect of reproductive factors, especially hormone
      replacement therapy (HRT) and its interaction with HLA-DRB1 *01 and/or *04
      alleles on the diagnosis of rheumatoid arthritis (RA) and the presence of anti
      cyclic citrullinated peptide (CCP) antibodies in women included in the ESPOIR
      cohort (early arthritis cohort). METHODS: 568 patients were included in the
      analyses, which were performed using logistic regression. RESULTS: HRT reduced
      the risk of RA due to the HLA-DRB1 *01 and/or *04 alleles from OR 1.88 (95% CI
      1.32 to 2.68, p<0.000) for HLA-DRB1 *01 and/or *04 alleles alone to OR 1.07 (95%
      CI 0.51 to 2.26, p=0.85) in women with HLA-DRB1 *01 and/or *04 alleles who
      received HRT. One explanation might be the protective effect of HRT on the
      presence of anti-CCP antibodies (OR 0.43, 95% CI 0.24 to 0.77, p<0.006). Other
      reproductive factors such as the number of pregnancies, menopause and age at
      menopause, age at menarche and a history of pregnancy with poor outcome were not
      associated with the diagnosis of RA and the presence of anti-CCP antibodies.
      CONCLUSION: HRT may reduce the risk of RA due to HLA-DRB1 *01 and/or *04 alleles
      by protecting against the production of anti-CCP antibodies.

PMID- 19740904
TI  - Effectiveness and retention rates of methotrexate in psoriatic arthritis in
      comparison with methotrexate-treated patients with rheumatoid arthritis.
AB  - OBJECTIVE: To examine the effectiveness and 2-year retention rates of
      methotrexate (MTX) in MTX naive patients with psoriatic arthritis (PsA). METHODS:
      Data on 430 patients with PsA participating in an ongoing longitudinal
      observational multicentre study in Norway were analysed. 1218 MTX naive patients
      with rheumatoid arthritis (RA) from the same study served as a reference
      population. Assessments included measures of disease activity (28 joint counts,
      acute phase reactants), health status and utility scores. Six-month effectiveness
      data were compared both by crude analyses and with adjustments for age, sex and
      the respective baseline values. Two-year drug survival was compared by Kaplan
      Meier and Cox regression analyses. RESULTS: After 6 months of MTX treatment, both
      patients with PsA and those with RA improved in most disease activity measures
      and patient reported outcomes. In the adjusted analysis, patients with PsA tended
      to have less improvement, but changes were in the same range as in patients with
      RA. Two-year retention rates of MTX therapy in patients with PsA and RA were 65%
      and 66%, respectively, with only minor differences in reported reasons for
      discontinuation. Lower age, longer disease duration and higher Modified Health
      Assessment Questionnaire (MHAQ) score and patient global assessment were
      independent predictors of MTX termination within the first 2 years of treatment.
      CONCLUSION: In this real-life study, MTX treatment was associated with
      improvement in disease activity and health-related quality of life in patients
      with PsA after 6 months of treatment. Retention rates of MTX were similar in PsA
      and RA.

PMID- 19740905
TI  - Evaluation of several ultrasonography scoring systems for synovitis and
      comparison to clinical examination: results from a prospective multicentre study
      of rheumatoid arthritis.
AB  - OBJECTIVES: To evaluate different global ultrasonographic (US) synovitis scoring
      systems as potential outcome measures of rheumatoid arthritis (RA) according to
      the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) filter.
      METHODS: To study selected global scoring systems, for the clinical, B mode and
      power Doppler techniques, the following joints were evaluated: 28 joints (28
      joint Disease Activity Score (DAS28)), 20 joints (metacarpophalangeals (MCPs) +
      metatarsophalangeals (MTPs)) and 38 joints (28 joints + MTPs) using either a
      binary (yes/no) or a 0-3 grade. The study was a prospective, 4-month duration
      follow-up of 76 patients with RA requiring anti-tumour necrosis factor (TNF)
      therapy (complete follow-up data: 66 patients). Intraobserver reliability was
      evaluated using the intraclass correlation coefficient (ICC), construct validity
      was evaluated using the Cronbach alpha test and external validity was evaluated
      using level of correlation between scoring system and C reactive protein (CRP).
      Sensitivity to change was evaluated using the standardised response mean.
      Discriminating capacity was evaluated using the standardised mean differences in
      patients considered by the doctor as significantly improved or not at the end of
      the study. RESULTS: Different clinimetric properties of various US scoring
      systems were at least as good as the clinical scores with, for example,
      intraobserver reliability ranging from 0.61 to 0.97 versus from 0.53 to 0.82,
      construct validity ranging from 0.76 to 0.89 versus from 0.76 to 0.88,
      correlation with CRP ranging from 0.28 to 0.34 versus from 0.28 to 0.35 and
      sensitivity to change ranging from 0.60 to 1.21 versus from 0.96 to 1.36 for US
      versus clinical scoring systems, respectively. CONCLUSION: This study suggests
      that US evaluation of synovitis is an outcome measure at least as relevant as
      physical examination. Further studies are required in order to achieve optimal US
      scoring systems for monitoring patients with RA in clinical trials and in
      clinical practice.

PMID- 19740906
TI  - Responsiveness of the Ankylosing Spondylitis Disease Activity Score (ASDAS) and
      clinical and MRI measures of disease activity in a 1-year follow-up study of
      patients with axial spondyloarthritis treated with tumour necrosis factor alpha
      inhibitors.
AB  - OBJECTIVES: To investigate construct validity and responsiveness of the novel
      ankylosing spondylitis (AS) disease activity score (ASDAS) in patients with
      spondyloarthritis (SpA). METHODS: In a 46-week prospective longitudinal
      multicentre study of 60 patients with SpA (80% men, median age 40 years (range 21
      62)) treated with tumour necrosis factor alpha (TNFalpha) inhibitors (infliximab,
      n=41; etanercept, n=13; adalimumab, n=6), the responsiveness of ASDAS,
      conventional clinical measures of disease activity and treatment response and the
      Berlin MRI sacroiliac joint (SIJ) and lumbar spine inflammation scores were
      compared. RESULTS: After 22 weeks, 58.3% of the patients were clinical responders
      (50% or 20 mm reduction in the Bath AS Disease Activity Index (BASDAI)). At
      baseline, clinical responders had significantly higher median (range) ASDAS than
      non-responders (4.15 (1.98-6.04) vs 2.99 (2.05-6.19), p=0.008). Changes in ASDAS
      correlated with changes in clinical measures of disease activity (including
      BASDAI (rho=0.76) and C-reactive protein (CRP) (0.79)), MRI SIJ inflammation
      (0.46) and MRI total inflammation scores (0.34). Patients with higher BASDAI or
      Assessment of SpondyloArthritis International Society (ASAS) responses obtained
      more profound reductions in ASDAS. ASDAS had the highest responsiveness with an
      effect size of 2.04 and a standardised response mean of 1.45, whereas BASDAI
      (effect size 1.86; standardised response mean 1.36) and CRP (effect size 0.63;
      standardised response mean 0.70) were less responsive. Linear regression showed
      that a change in BASDAI of 20 mm or 50% corresponded to a change in ASDAS of 1.38
      and 1.95, respectively. CONCLUSION: ASDAS demonstrates construct validity and
      high responsiveness during treatment with TNFalpha inhibitors in patients with
      SpA. The proposed thresholds for disease activity and treatment response need
      further validation. Trial registration number NCT00133315.

PMID- 19740907
TI  - Cardiac resynchronization therapy upgrade in a patient with dextrocardia and
      situs inversus.
AB  - Cardiac resynchronization therapy in patients with congenital heart disease can
      be technically challenging. We report a case of upgrade of an implantable
      cardioverter defibrillator to a resynchronization device, in a patient with
      dextrocardia and situs inversus. The procedure was successfully performed without
      complication, using a conventional approach and standard equipment.

PMID- 19740909
TI  - Swine flu and antibiotics.
AB  - Health services worldwide are likely to be hard-pressed by swine flu-related
      illness in the months ahead. Secondary infections with Streptococcus pneumoniae,
      other streptococci (e.g. Streptococcus pyogenes), Haemophilus influenzae and
      Staphylococcus aureus are likely to be important causes of morbidity and
      mortality. The UK Department of Health recently published clinical pathways for
      the management of swine flu. Suggested severity criteria have not been validated
      in respiratory infection and are different from those previously published.
      Antibiotics are recommended for all patients assessed at hospital, regardless of
      severity of illness; cephalosporins or quinolones are suggested for inpatients
      with pneumonia. These recommendations will jeopardize recent decreases in
      Clostridium difficile-associated diarrhoea (CDAD) and methicillin-resistant S.
      aureus (MRSA) in UK hospitals. This article, written on behalf of the BSAC
      Council, considers these recommendations and provides alternative antibiotic
      regimens for a range of clinical scenarios.

PMID- 19740910
TI  - Mitochondrial toxicity in HIV-infected patients both off and on antiretroviral
      treatment: a continuum or distinct underlying mechanisms?
AB  - Mitochondrial toxicity contributes to serious adverse effects observed in HIV
      infected individuals treated with nucleoside reverse transcriptase inhibitors
      (NRTIs). However, similar mitochondrial abnormalities have recently been found
      even in treatment-naive patients, suggesting that chronic HIV per se could
      contribute to the toxicity observed in NRTI-exposed individuals. This review
      gives a current status of the field, with particular focus on recent observations
      suggesting that distinct mechanisms might cause such toxicity in both NRTI
      exposed individuals and those naive to antiretroviral treatment.

PMID- 19740911
TI  - Emergence of blaKPC-containing Klebsiella pneumoniae in a long-term acute care
      hospital: a new challenge to our healthcare system.
AB  - OBJECTIVES: To characterize isolates of Klebsiella pneumoniae producing KPC
      carbapenemase (KPC-Kp) associated with an outbreak in a long-term acute care
      hospital (LTACH) in South Florida. METHODS: During 21 March to 20 April 2008, 241
      K. pneumoniae isolates detected at Integrated Regional Laboratories (Ft.
      Lauderdale, FL) for which the ertapenem MICs were > or =4 mg/L were studied. PCR,
      cloning and sequence analysis were used to detect bla(KPC) and to characterize
      the beta-lactamase and outer membrane proteins (Omps). The expression level of
      KPC enzymes was studied by immunoblotting. Genetic relatedness of isolates was
      investigated with rep-PCR and PFGE. Clinical records of patients were
      investigated. RESULTS: Seven KPC-Kp strains were isolated from different patients
      located at a single LTACH, with a further three isolates being recovered from
      patients at different hospitals. All KPC-Kp isolates in patients from the LTACH
      and from one hospital patient were genetically related and shared PFGE patterns
      that clustered with known sequence type (ST) 258 strains. These strains were
      highly resistant to carbapenems (MICs > or = 32 mg/L) due to an increased level
      of KPC expression and loss of Omps. Rectal colonization was documented in all
      LTACH patients with KPC-Kp isolates. Treatment failures were common (crude
      mortality rate of 69%). Active surveillance and enhanced infection control
      practices terminated the KPC-Kp outbreak. CONCLUSIONS: The detection of KPC-Kp in
      an LTACH represents a serious infection control and therapeutic challenge in a
      new clinical setting. The speed at which the epidemic of KPC-Kp is spreading in
      our healthcare system mandates urgent action.

PMID- 19740912
TI  - massXpert 2: a cross-platform software environment for polymer chemistry
      modelling and simulation/analysis of mass spectrometric data.
AB  - Since the middle of the 90s, mass spectrometry has evolved into an almost
      indispensable tool in structural studies on an ever-growing variety of (bio
      )polymers, of which proteins, sugars and nucleic acids are the most prominent.
      Since the first public release of massXpert, the advances of mass spectrometry
      have motivated continuous and thorough maintenance of that software, in the form
      of two full software rewrites, culminating with massXpert 2, which we describe in
      this report. We shall describe the profound changes in massXpert that were
      performed so as to keep up with the technical advances in mass spectrometry since
      a decade. AVAILABILITY: The massXpert 2 software is an open source and free
      software project hosted at http://www.massxpert.org.

PMID- 19740913
TI  - CDKL5 influences RNA splicing activity by its association to the nuclear speckle
      molecular machinery.
AB  - Mutations in the human X-linked cyclin-dependent kinase-like 5 (CDKL5) gene have
      been shown to cause severe neurodevelopmental disorders including infantile
      spasms, encephalopathy, West-syndrome and an early-onset variant of Rett
      syndrome. CDKL5 is a serine/threonine kinase whose involvement in Rett syndrome
      can be inferred by its ability to directly bind and mediate phosphorylation of
      MeCP2. However, it remains to be elucidated how CDKL5 exerts its function. Here,
      we report that CDKL5 localizes to specific nuclear foci referred to as nuclear
      speckles in both cell lines and tissues. These sub-nuclear structures are
      traditionally considered as storage/modification sites of pre-mRNA splicing
      factors. Interestingly, we provide evidence that CDKL5 regulates the dynamic
      behaviour of nuclear speckles. Indeed, CDKL5 overexpression leads to nuclear
      speckle disassembly, and this event is strictly dependent on its kinase activity.
      Conversely, its down-regulation affects nuclear speckle morphology leading to
      abnormally large and uneven speckles. Similar results were obtained for primary
      adult fibroblasts isolated from CDKL5-mutated patients. Altogether, these
      findings indicate that CDKL5 controls nuclear speckle morphology probably by
      regulating the phosphorylation state of splicing regulatory proteins. Nuclear
      speckles are dynamic sites that can continuously supply splicing factors to
      active transcription sites, where splicing occurs. Notably, we proved that CDKL5
      influences alternative splicing, at least as proved in heterologous minigene
      assays. In conclusion, we provide evidence that CDKL5 is involved indirectly in
      pre-mRNA processing, by controlling splicing factor dynamics. These findings
      identify a biological process whose disregulation might affect neuronal
      maturation and activity in CDKL5-related disorders.

PMID- 19740914
TI  - Age-related faecal calprotectin, lactoferrin and tumour M2-PK concentrations in
      healthy volunteers.
AB  - OBJECTIVE: Measurement of the faecal markers calprotectin, lactoferrin and tumour
      M2-PK has been reported to be useful in the diagnosis and management of a range
      of gastrointestinal disorders in both children and adults. The aim of this study
      was to investigate the requirement for age-related reference ranges. METHODS:
      Faecal samples were obtained from 132 healthy subjects and analysis of
      calprotectin, lactoferrin and tumour M2-PK performed using commercially available
      enzyme-linked immunosorbent assay. RESULTS: In the healthy subjects median
      concentrations were as follows: for calprotectin - 2-9 y, 34 microg/g, 10-59 y,
      22 microg/g and > or =60 y, 27 microg/g; for lactoferrin - 2-9 y, 2.2 microg/g, >
      or =10 y, 0.5 microg/g; and for tumour M2-PK all subjects <1 U/mL. Significant
      differences between age groups for different markers resulted in the following
      age-related reference ranges: calprotectin - 2-9 y, <166 microg/g, 10-59 y, <51
      microg/g, > or =60 y, <112 microg/g; lactoferrin - 2-9 y, <29 microg/g, > or =10
      y <4.6 microg/g. CONCLUSION: In healthy individuals, we found there to be
      variation in the faecal inflammatory markers calprotectin and lactoferrin with
      age. For both calprotectin and lactoferrin children aged 2-9 y had significantly
      higher concentrations than subjects aged >/=10 y. For calprotectin but not
      lactoferrin, adults > or =60 years had a higher concentration than those aged 10
      59 y. There was no change with age in the metabolomic marker faecal tumour M2-PK
      in healthy subjects. The knowledge of age-related reference ranges in healthy
      subjects is important to fully interpret changes in gastrointestinal disease.

PMID- 19740915
TI  - Combined cyclosporine and prednisolone therapy in adult patients with the first
      relapse of minimal-change nephrotic syndrome.
AB  - BACKGROUND: Although minimal-change nephrotic syndrome (MCNS) is highly steroid
      responsive, some patients show frequent relapses, necessitating administration of
      repeated courses of prednisolone (PSL) at high doses. The adverse effects of long
      term PSL treatment include osteoporosis, infection, diabetes, cataract, etc.,
      most of which are serious. It is therefore necessary to establish useful
      strategies to reduce the PSL dose. METHODS: Patients with the first relapse of
      MCNS were randomly assigned to two groups, namely, the CyA (AUC 1700-2000 ng/ml)
      + PSL (0.8 mg/kg/day) group (n = 26) and the PSL alone (PSL) (1.0 mg/kg/day)
      group (n = 26), and the clinical characteristics were compared between the two
      groups. All patients used C2 for CyA monitoring. RESULTS: A significant decrease
      of the urinary protein excretion (P = 0.02) and serum total cholesterol (P =
      0.003) was observed at 2 weeks from the first relapse in the CyA + PSL group. The
      increase in the serum total protein (P = 0.03) and serum albumin (P = 0.007) as
      compared with that in the PSL group was also observed in the CyA + PSL group at
      this time-point. The time to remission in the CyA + PSL group was shorter than
      that in the PSL group (P = 0.006). CONCLUSION: It was possible to obtain early
      remission and reduce the PSL dose with combined CyA and PSL therapy in patients
      with MCNS.

PMID- 19740916
TI  - Investigating infertility.

PMID- 19740917
TI  - Eye sign in an 18 year old man with psychosis.

PMID- 19740920
TI  - Inflow boundary profile prescription for numerical simulation of nasal airflow.
AB  - Knowledge of how air flows through the nasal passages relies heavily on model
      studies, as the complexity and relative inaccessibility of the anatomy prevents
      detailed in vivo measurement. Almost all models to date fail to incorporate the
      geometry of the external nose, instead employing a truncated inflow. Typically,
      flow is specified to enter the model domain either directly at the nares
      (nostrils), or via an artificial pipe inflow tract attached to the nares. This
      study investigates the effect of the inflow geometry on flow predictions during
      steady nasal inspiration. Models that fully replicate the internal and external
      nasal airways of two anatomically distinct subjects are used as a reference to
      compare the effects of common inflow treatments on physiologically relevant
      quantities including regional wall shear stress and particle residence time
      distributions. Inflow geometry truncation is found to affect flow predictions
      significantly, though slightly less so for the subject displaying more pronounced
      passage area contraction up to the internal nasal valve. For both subject
      geometries, a tapered pipe inflow provides a better approximation to the natural
      inflow than a blunt velocity profile applied to the nares. Computational
      modelling issues are also briefly outlined, by comparing quantities predicted
      using different surface tessellations, and by evaluation of domain-splitting
      techniques.

PMID- 19740921
TI  - Control of airborne infectious diseases in ventilated spaces.
AB  - We protect ourselves from airborne cross-infection in the indoor environment by
      supplying fresh air to a room by natural or mechanical ventilation. The air is
      distributed in the room according to different principles: mixing ventilation,
      displacement ventilation, etc. A large amount of air is supplied to the room to
      ensure a dilution of airborne infection. Analyses of the flow in the room show
      that there are a number of parameters that play an important role in minimizing
      airborne cross-infection. The air flow rate to the room must be high, and the air
      distribution pattern can be designed to have high ventilation effectiveness.
      Furthermore, personalized ventilation may reduce the risk of cross-infection, and
      in some cases, it can also reduce the source of infection. Personalized
      ventilation can especially be used in hospital wards, aircraft cabins and, in
      general, where people are in fixed positions.

PMID- 19740923
TI  - Optimal and robust control of invasive alien species spreading in homogeneous
      landscapes.
AB  - Government agencies lack robust modelling tools to manage the spread of invasive
      alien species (IAS). In this paper, we combine optimal control and simulation
      methods with biological invasion spread theory to estimate the type of optimal
      policy and switching point of control efforts against a spreading IAS. We employ
      information-gap (info-gap) theory to assess how the optimal solutions differ from
      a policy that is most robustly immune to unacceptable outcomes. The model is
      applied to the potential invasion of the Colorado potato beetle in the UK. Under
      no uncertainty, we demonstrate that for many of the parameter combinations the
      optimal control policy corresponds to slowing down the invasion. The info-gap
      analysis shows that eradication policies identified as optimal under no
      uncertainty are robustly the best policies even under severe uncertainty, i.e.
      even if they are likely to turn into slowing down policies. We also show that the
      control of satellite colonies, if identified as optimal under no uncertainty,
      will also be a robust slowing down policy for IAS that can spread by long
      distance dispersal even for relatively ineffective control measures. The results
      suggest that agencies adopt management strategies that are robustly optimal,
      despite the severe uncertainties they face.

PMID- 19740922
TI  - Recent advances in the analysis of behavioural organization and interpretation as
      indicators of animal welfare.
AB  - While the incorporation of mathematical and engineering methods has greatly
      advanced in other areas of the life sciences, they have been under-utilized in
      the field of animal welfare. Exceptions are beginning to emerge and share a
      common motivation to quantify 'hidden' aspects in the structure of the behaviour
      of an individual, or group of animals. Such analyses have the potential to
      quantify behavioural markers of pain and stress and quantify abnormal behaviour
      objectively. This review seeks to explore the scope of such analytical methods as
      behavioural indicators of welfare. We outline four classes of analyses that can
      be used to quantify aspects of behavioural organization. The underlying
      principles, possible applications and limitations are described for: fractal
      analysis, temporal methods, social network analysis, and agent-based modelling
      and simulation. We hope to encourage further application of analyses of
      behavioural organization by highlighting potential applications in the assessment
      of animal welfare, and increasing awareness of the scope for the development of
      new mathematical methods in this area.

PMID- 19740924
TI  - Herd immunity acquired indirectly from interactions between the ecology of
      infectious diseases, demography and economics.
AB  - Patterns of morbidity and mortality around the globe are determined by
      interactions between infectious diseases and systematic human socioeconomic
      processes. The most obvious of these patterns is that the greatest burdens of
      infectious diseases are found among the poor, who lack the basic resources for
      disease prevention and treatment. Yet, it is becoming increasingly clear that
      many infectious diseases are themselves causes of poverty owing to their effects
      on labour productivity. A particularly subtle phenomenon that receives little
      attention in the epidemiology literature and is especially important for poor
      communities is the role of the birth rate as an important direct cause of high
      disease burdens. Because of their high rates of transmission and life-long
      immunity, the persistence of many child diseases such as measles relies on high
      rates of reproduction as their source of susceptible individuals. Thus, there are
      significant direct health benefits of lower fertility rates, which are further
      enhanced by interactions with economic processes. Indeed, fertility, poverty and
      disease all interact with each other in important and predictable ways that can
      be built into traditional disease ecology models. We present such a model here
      that provides insights into the long-term effect of policy interventions. For
      example, because of indirect income effects, herd immunity may be acquired with
      lower vaccine coverage than previously thought. Reductions in the disease burden
      can also occur through lower fertility. Our model thus provides a disease ecology
      framework that is useful for the analysis of demographic transitions.

PMID- 19740925
TI  - Should I have an H1N1 flu vaccination after Guillain-Barre syndrome?

PMID- 19740933
TI  - Assessing the onset of pre-eclampsia in the hospital day unit: summary of the pre
      eclampsia guideline (PRECOG II).

PMID- 19740935
TI  - Abstracts of the College of Emergency Medicine Autumn Conference. London, United
      Kingdom. September 16-18, 2009.

PMID- 19740934
TI  - Exhaustive search for over-represented DNA sequence motifs with CisFinder.
AB  - We present CisFinder software, which generates a comprehensive list of motifs
      enriched in a set of DNA sequences and describes them with position frequency
      matrices (PFMs). A new algorithm was designed to estimate PFMs directly from
      counts of n-mer words with and without gaps; then PFMs are extended over gaps and
      flanking regions and clustered to generate non-redundant sets of motifs. The
      algorithm successfully identified binding motifs for 12 transcription factors
      (TFs) in embryonic stem cells based on published chromatin immunoprecipitation
      sequencing data. Furthermore, CisFinder successfully identified alternative
      binding motifs of TFs (e.g. POU5F1, ESRRB, and CTCF) and motifs for known and
      unknown co-factors of genes associated with the pluripotent state of ES cells.
      CisFinder also showed robust performance in the identification of motifs that
      were only slightly enriched in a set of DNA sequences.

PMID- 19740970
TI  - Erythrocyte pyridoxamine phosphate oxidase activity: a potential biomarker of
      riboflavin status?
AB  - BACKGROUND: Riboflavin status is commonly measured by the in vitro stimulation of
      erythrocyte glutathione reductase with flavin adenine dinucleotide and expressed
      as an erythrocyte glutathione reductase activation coefficient (EGRAC). However,
      this assay is insensitive to poor riboflavin status in subjects with glucose-6
      phosphate dehydrogenase (G6PD) deficiency. Because G6PD deficiency is common in
      parts of the world where ariboflavinosis is endemic, it is important to have a
      measure of riboflavin status that is unaffected by differences in G6PD status.
      OBJECTIVE: The objective was to further develop and validate a fluorometric assay
      for pyridoxamine phosphate oxidase (PPO) activity as a measure of riboflavin
      status. DESIGN: A fluorometric assay was optimized for the flavin-dependent
      enzyme PPO in erythrocytes. Hemolysates from a previous riboflavin intervention
      study (2- and 4-mg riboflavin supplements) were used to investigate the
      responsiveness of the method to changes in riboflavin intake. RESULTS: PPO
      activity and the PPO activation coefficient (PPOAC) were used to assess
      riboflavin status. Both PPO activity and PPOAC responded to riboflavin
      supplements (P < 0.01), but only PPO showed a dose response (P < 0.001). The
      change from baseline to after the intervention in PPOAC and PPO enzyme activity
      was significantly inversely correlated (P < 0.001). Both PPO activity and PPOAC
      were strongly correlated with EGRAC (P < 0.001). Additionally, both PPOAC and
      EGRAC showed a significant inverse correlation with dietary riboflavin intake (P
      < 0.01); PPO activity was positively correlated with riboflavin intake (P <
      0.01). CONCLUSION: PPO activity could be used as a biomarker for measuring
      riboflavin status, especially in populations with a high prevalence of G6PD
      deficiency. This trial is registered at www.isrctn.org as ISRCTN35811298.

PMID- 19740972
TI  - Adiposity and human regional body temperature.
AB  - BACKGROUND: Human obesity is associated with increased heat production; however,
      subcutaneous adipose tissue provides an insulating layer that impedes heat loss.
      To maintain normothermia, therefore, obese individuals must increase their heat
      dissipation. OBJECTIVE: The objective was to test the hypothesis that temperature
      in a heat-dissipating region of the hand is elevated in obese adults. DESIGN:
      Obese [body mass index (in kg/m(2)) > or = 30] and normal-weight (NW; body mass
      index = 18-25) adults were studied under thermoneutral conditions at rest. Core
      body temperature was measured by using ingested telemetric capsules. The
      temperatures of the third fingernail bed of the right hand and of abdominal skin
      from an area 1.5 cm inferior to the umbilicus were determined by using infrared
      thermography. Abdominal skin temperatures were also measured via adhesive
      thermistors that were placed over a prominent skin-surface blood vessel and over
      an adjacent nonvessel location. The groups were compared by analysis of
      covariance with age, sex, race, and room temperature as covariates. RESULTS: Core
      temperature did not differ significantly between the 23 obese and 13 NW
      participants (P = 0.74). However, infrared thermography-measured fingernail-bed
      temperature was significantly higher in obese subjects than in NW subjects (33.9
      +/- 0.7 degrees C compared with 28.6 +/- 0.9 degrees C; P < 0.001). Conversely,
      infrared thermography-measured abdominal skin temperature was significantly lower
      in obese subjects than in NW subjects (31.8 +/- 0.2 degrees C compared with 32.8
      +/- 0.3 degrees C; P = 0.02). Nonvessel abdominal skin temperatures measured by
      thermistors were also lower in obese subjects (P = 0.04). CONCLUSIONS: Greater
      subcutaneous abdominal adipose tissue in obese adults may provide a significant
      insulating layer that blunts abdominal heat transfer. Augmented heat release from
      the hands may offset heat retention in areas of the body with greater adiposity,
      thereby helping to maintain normothermia in obesity. This trial was registered at
      clinicaltrials.gov as NCT00266500.

PMID- 19740971
TI  - Activity energy expenditure and change in body composition in late life.
AB  - BACKGROUND: Change in body composition, specifically loss of fat-free mass and
      gain in fat mass, in older adults is a major pathway leading to the onset of
      functional decline and physical disability. OBJECTIVE: The objective was to
      determine the association of activity-related energy expenditure with change in
      body mass and composition among older men and women. DESIGN: Total energy
      expenditure (TEE) was assessed over 2 wk by using the doubly labeled water method
      in 302 community-dwelling older adults aged 70-82 y. Resting metabolic rate (RMR)
      was measured by using indirect calorimetry, and the thermic effect of meals was
      estimated at 10% of TEE. Activity energy expenditure (AEE) was calculated as
      [TEE(0.9) - RMR]. Total body mass, fat-free mass (FFM), and fat mass (FM) were
      assessed by dual-energy X-ray absorptiometry annually over a mean (+/-SD) of 4.9
      +/- 1.3 y. RESULTS: In multivariate models adjusted for baseline age, smoking
      status, and race, men and women had a decline (in kg/y) in body mass (men: -0.34,
      95% CI: -0.71, 0.02; women: -0.45, 95% CI: -0.71, -0.19) and FFM (men: -0.48, 95%
      CI: -0.67, -0.29; women: -0.14, 95% CI: -0.026, -0.03). No changes (in kg/y) were
      observed in FM (men: 0.14, 95% CI: -0.10, 0.38; women: -0.28, 95% CI: -0.49, 
      0.07). In men and women, higher AEE at baseline was associated with greater FFM.
      The average change in these outcomes (ie, slope), however, was similar across
      tertiles of AEE. CONCLUSIONS: These data suggest that accumulated energy
      expenditure from all physical activities is associated with greater FFM, but the
      effect does not alter the trajectory of FFM change in late life.

PMID- 19740973
TI  - Sugar-sweetened beverage consumption and the progression of chronic kidney
      disease in the Multi-Ethnic Study of Atherosclerosis (MESA).
AB  - BACKGROUND: Recent studies have examined sugar-sweetened soda consumption in
      relation to early markers of kidney disease, but to date there have been no
      investigations of whether sugar-sweetened beverage consumption affects
      preexistent chronic kidney disease (CKD). OBJECTIVE: This prospective cohort
      study of 447 participants in the Multi-Ethnic Study of Atherosclerosis (MESA)
      with preexistent CKD examined the association between sugar-sweetened beverage
      consumption (<1 drink/wk, 1-6 drinks/wk, and > or =1 drink/d) and progression of
      CKD. DESIGN: beta-Coefficients for continuous outcomes of changes in estimated
      glomerular filtration rate (eGFR) and urinary albumin to creatinine ratio (UACR)
      were calculated by using linear regression. Odds ratios for binary outcomes of
      accelerated decline in eGFR, defined as >2 mL x min(-1) x 1.73 m(-2) per year,
      and clinically significant progression of albuminuria (defined as attainment of
      UACR > or =30 mg/g for participants without microalbuminuria at visit 1 or a > or
      =25% increase in UACR for participants with baseline microalbuminuria) were
      evaluated by using logistic regression. RESULTS: The mean (+/-SD) baseline eGFR
      was 52 +/- 6 mL x min(-1) x 1.73 m(-2) per year, and median baseline UACR was 6.3
      mg/g (interquartile range: 3.5-17.6). Univariate and multivariate analyses showed
      no association between sugar-sweetened beverage consumption and rate of eGFR
      decline or changes in urinary albumin to creatinine ratio. The multivariate odds
      ratios comparing participants who drank > or =1 sugary beverage daily with those
      who drank < or =1 beverage weekly were 0.62 (95% CI: 0.27, 1.41) for accelerated
      eGFR decline and 1.51 (95% CI: 0.49, 4.62) for clinically significant progression
      of albuminuria. CONCLUSION: A higher consumption of sugar-sweetened beverages was
      not associated with disease progression, on the basis of either eGFR or the
      urinary albumin to creatinine ratio, in MESA participants with preexistent CKD.

PMID- 19740974
TI  - Plasma hepcidin is a modest predictor of dietary iron bioavailability in humans,
      whereas oral iron loading, measured by stable-isotope appearance curves,
      increases plasma hepcidin.
AB  - BACKGROUND: Plasma hepcidin appears to be a major regulator of iron absorption
      and homeostasis, but there are few data in humans. OBJECTIVES: With the use of
      iron stable isotopes, we aimed to determine whether circulating hepcidin predicts
      dietary iron bioavailability, to quantify the amount of absorbed iron after oral
      iron loading, and to measure the plasma hepcidin response. DESIGN: In the first
      study, young women (n = 98) with an iron status varying from iron deficiency
      anemia to iron sufficiency (women with serum ferritin concentrations 25-40
      microg/L were not included) were given stable isotope-labeled test meals (n =
      196) containing ferrous sulfate, ferrous fumarate, or ferric pyrophosphate, after
      which plasma hepcidin and iron bioavailability were measured. In the second
      study, iron-sufficient men (n = 4) were given 3.8- and 60-mg oral doses of
      labeled ferrous sulfate. The stable isotope appearance curve was determined, and
      the plasma hepcidin response was measured over 6 h. RESULTS: In study 1, plasma
      hepcidin and plasma ferritin were strongly correlated (r = 0.79, P < 0.001).
      Plasma hepcidin significantly, but modestly, predicted iron bioavailability from
      ferrous sulfate and ferrous fumarate (r = -0.51 and -0.46, respectively; P <
      0.0001) but not from ferric pyrophosphate (r = -0.30, P = 0.056, respectively).
      In study 2, the 3.8-mg dose increased mean circulating absorbed iron to a peak of
      0.42 micromol/L at 60 min but did not increase plasma hepcidin, The 60-mg dose
      increased mean circulating absorbed iron to a peak of 5.9 micromol/L at 120 min
      and produced an approximately 30% increase in mean plasma hepcidin at 6 h (P <
      0.01). CONCLUSIONS: Plasma hepcidin is only a modest predictor of dietary iron
      bioavailability in humans. Oral iron loading, measured by stable-isotope
      appearance curves, increases circulating hepcidin.

PMID- 19740976
TI  - Measurement of postprandial interleukin-6 by using a catheter: what does it tell
      us?

PMID- 19740975
TI  - Blunting of insulin inhibition of proteolysis in legs of older subjects may
      contribute to age-related sarcopenia.
AB  - BACKGROUND: Reduced postprandial muscle proteolysis is mainly due to increased
      insulin availability. Whether rates of proteolysis in response to low physiologic
      doses of insulin are affected by aging is unknown. OBJECTIVES: We tested the
      hypothesis that suppression of leg protein breakdown (LPB) by insulin is blunted
      in older subjects, together with blunted activation of Akt-protein kinase B
      (PKB). DESIGN: Groups of 8 young [mean (+/-SD) age: 24.5 +/- 1.8 y] and older
      (65.0 +/- 1.3 y) participants were studied during euglycemic (5 mmol/L),
      isoaminoacidemic (blood leucine approximately 120 micromol/L) clamp procedures at
      plasma insulin concentrations of approximately 5 and approximately 15 microIU/mL
      for 1.5 h. Leg amino acid balance, whole-leg protein turnover (as dilution of
      amino acid tracers), and muscle protein synthesis were measured with D(5)
      phenylalanine and [1,2-(13)C(2)]leucine. The kinase activity of muscle Akt-PKB
      and the extent of phosphorylation of signaling proteins associated with the mTOR
      (mammalian target of rapamycin) pathway were measured before and after the clamp
      procedures. RESULTS: Basal LPB rates were not different between groups (66 +/- 11
      compared with 51 +/- 10 nmol leucine x 100 mL leg(-1) x min(-1) and 30 +/- 5
      compared with 24 +/- 4 nmol phenylalanine x 100 mL leg(-1) x min(-1) in young and
      older groups, respectively). However, although insulin at approximately 15
      microIU/mL lowered LPB by 47% in the young subjects (P < 0.05) and abolished the
      negative leg amino acid balance, this caused only a 12% fall (P > 0.05) in the
      older group. Akt-PKB activity mirrored decreases in LPB. No differences were seen
      in muscle protein synthesis or associated anabolic signaling phosphoproteins.
      CONCLUSIONS: At moderate availability, the effect of insulin on LPB is diminished
      in older human beings, and this effect may be mediated through blunted Akt-PKB
      activation.

PMID- 19740977
TI  - Effects of force magnitude on tooth movement: an experimental study in rabbits.
AB  - The aim of the present study was to investigate the effects of two different
      force levels on the amount of total and daily tooth movement in rabbits and to
      determine whether any increase in tooth movement is equal to the increase in
      force. Forces of approximately 20 (group I) and 60 (group II) g (19.6 and 58.8
      cN) were applied to the upper central incisors of 25 young adult (14 weeks of
      age) New Zealand female rabbits. The distance between the incisors was measured
      daily from the mid-levels of the crowns using a digital calliper for 20 days.
      Analysis of variance and Bonferroni multiple range test were used for statistical
      analyses. The distance between the teeth in group II was significantly greater
      than that in group I during the first 3 days. Between days 4 and 14, no
      significant difference was observed. During the last 6 days, except for day 19,
      tooth movement in group II again increased, resulting in the distance between the
      teeth being greater in group II. The mean total opening was 3.98 +/- 0.59 mm in
      group I and 4.82 +/- 0.82 mm in group II, and the mean difference was
      approximately 0.8 mm. The results of this study show that there was a close
      relationship between tooth movement and force magnitude. However, higher forces
      did not produce force-equal tooth movements.

PMID- 19740978
TI  - Crystallographic definition of the epitope promiscuity of the broadly
      neutralizing anti-human immunodeficiency virus type 1 antibody 2F5: vaccine
      design implications.
AB  - The quest to create a human immunodeficiency virus type 1 (HIV-1) vaccine capable
      of eliciting broadly neutralizing antibodies against Env has been challenging.
      Among other problems, one difficulty in creating a potent immunogen resides in
      the substantial overall sequence variability of the HIV envelope protein. The
      membrane-proximal region (MPER) of gp41 is a particularly conserved tryptophan
      rich region spanning residues 659 to 683, which is recognized by three broadly
      neutralizing monoclonal antibodies (bnMAbs), 2F5, Z13, and 4E10. In this study,
      we first describe the variability of residues in the gp41 MPER and report on the
      invariant nature of 15 out of 25 amino acids comprising this region.
      Subsequently, we evaluate the ability of the bnMAb 2F5 to recognize 31 varying
      sequences of the gp41 MPER at a molecular level. In 19 cases, resulting crystal
      structures show the various MPER peptides bound to the 2F5 Fab'. A variety of
      amino acid substitutions outside the 664DKW666 core epitope are tolerated.
      However, changes at the 664DKW666 motif itself are restricted to those residues
      that preserve the aspartate's negative charge, the hydrophobic alkyl-pi stacking
      arrangement between the beta-turn lysine and tryptophan, and the positive charge
      of the former. We also characterize a possible molecular mechanism of 2F5 escape
      by sequence variability at position 667, which is often observed in HIV-1 clade C
      isolates. Based on our results, we propose a somewhat more flexible molecular
      model of epitope recognition by bnMAb 2F5, which could guide future attempts at
      designing small-molecule MPER-like vaccines capable of eliciting 2F5-like
      antibodies.

PMID- 19740979
TI  - Detection of PrPsc in blood from sheep infected with the scrapie and bovine
      spongiform encephalopathy agents.
AB  - The role of blood in the iatrogenic transmission of transmissible spongiform
      encephalopathy (TSE) or prion disease has become an increasing concern since the
      reports of variant Creutzfeldt-Jakob disease (vCJD) transmission through blood
      transfusion from humans with subclinical infection. The development of highly
      sensitive rapid assays to screen for prion infection in blood is of high priority
      in order to facilitate the prevention of transmission via blood and blood
      products. In the present study we show that PrP(sc), a surrogate marker for TSE
      infection, can be detected in cells isolated from the blood from naturally and
      experimentally infected sheep by using a rapid ligand-based immunoassay. In sheep
      with clinical disease, PrP(sc) was detected in the blood of 55% of scrapie agent
      infected animals (n = 80) and 71% of animals with bovine spongiform
      encephalopathy (n = 7). PrP(sc) was also detected several months before the onset
      of clinical signs in a subset of scrapie agent-infected sheep, followed from 3
      months of age to clinical disease. This study confirms that PrP(sc) is associated
      with the cellular component of blood and can be detected in preclinical sheep by
      an immunoassay in the absence of in vitro or in vivo amplification.

PMID- 19740980
TI  - Antagonism to and intracellular sequestration of human tetherin by the human
      immunodeficiency virus type 2 envelope glycoprotein.
AB  - Tetherin (CD317/BST-2), an interferon-induced membrane protein, restricts the
      release of nascent retroviral particles from infected cell surfaces. While human
      immunodeficiency virus type 1 (HIV-1) encodes the accessory gene vpu to overcome
      the action of tetherin, the lineage of primate lentiviruses that gave rise to HIV
      2 does not. It has been previously reported that the HIV-2 envelope glycoprotein
      has a Vpu-like function in promoting virus release. Here we demonstrate that the
      HIV-2 Rod envelope glycoprotein (HIV-2 Rod Env) is a tetherin antagonist.
      Expression of HIV-2 Rod Env, but not that of HIV-1 or the closely related simian
      immunodeficiency virus (SIV) SIVmac1A11, counteracts tetherin-mediated
      restriction of Vpu-defective HIV-1 in a cell-type-specific manner. This
      correlates with the ability of the HIV-2 Rod Env to mediate cell surface
      downregulation of tetherin. Antagonism requires an endocytic motif conserved
      across HIV/SIV lineages in the gp41 cytoplasmic tail, but specificity for
      tetherin is governed by extracellular determinants in the mature Env protein.
      Coimmunoprecipitation studies suggest an interaction between HIV-2 Rod Env and
      tetherin, but unlike studies with Vpu, we found no evidence of tetherin
      degradation. In the presence of HIV-2 Rod Env, tetherin localization is
      restricted to the trans-Golgi network, suggesting Env-mediated effects on
      tetherin trafficking sequester it from virus assembly sites on the plasma
      membrane. Finally, we recapitulated these observations in HIV-2-infected CD4+ T
      cell lines, demonstrating that tetherin antagonism and sequestration occur at
      physiological levels of Env expression during virus replication.

PMID- 19740981
TI  - Histone deacetylases 1 and 2 are phosphorylated at novel sites during varicella
      zoster virus infection.
AB  - ORF66p, a virion-associated varicella-zoster virus (VZV) protein, is a member of
      a conserved Alphaherpesvirinae kinase family with homology to herpes simplex
      virus US3 kinase. Expression of ORF66p in cells infected with VZV or an
      adenovirus expressing only ORF66p results in hyperphosphorylation of histone
      deacetylase 1 (HDAC1) and HDAC2. Mapping studies reveal that phosphorylation is
      at a unique conserved Ser residue in the C terminus of both HDACs. This
      modification requires an active kinase domain in ORF66p, as neither protein is
      phosphorylated in cells infected with VZV lacking kinase activity. However,
      hyperphosphorylation appears to occur indirectly, as within the context of in
      vitro kinase reactions, purified ORF66p phosphorylates a peptide derived from
      ORF62p, a known substrate, but does not phosphorylate HDAC. These results support
      a model where ORF66p is necessary but not sufficient to effect
      hyperphosphorylation of HDAC1 and HDAC2.

PMID- 19740982
TI  - Structural and functional analysis of hepatitis C virus strain JFH1 polymerase.
AB  - The hepatitis C virus (HCV) isolate JFH1 represents the only cloned wild-type
      sequence capable of efficient replication in cell culture, as well as in
      chimpanzees. Previous reports have pointed to the viral polymerase NS5B as a
      major determinant for efficient replication of this isolate. To understand the
      underlying mechanisms, we expressed and purified NS5B of JFH1 and of the closely
      related isolate J6, which replicates below the limit of detection in cell
      culture. The JFH1 enzyme exhibited a 5- to 10-fold-higher specific activity in
      vitro, consistent with the polymerase activity itself contributing to efficient
      replication of JFH1. The higher in vitro activity of the JFH1 enzyme was not due
      to increased RNA binding, elongation rate, or processivity of the polymerase but
      to higher initiation efficiency. By using homopolymeric and heteropolymeric
      templates, we found that purified JFH1 NS5B was significantly more efficient in
      de novo initiation of RNA synthesis than the J6 counterpart, particularly at low
      GTP concentrations, probably representing an important prerequisite for the rapid
      replication kinetics of JFH1. Furthermore, we solved the crystal structure of
      JFH1 NS5B, which displays a very closed conformation that is expected to
      facilitate de novo initiation. Structural analysis shows that this closed
      conformation is stabilized by a sprinkle of substitutions that together promote
      extra hydrophobic interactions between the subdomains "thumb" and "fingers."
      These analyses provide deeper insights into the initiation of HCV RNA synthesis
      and might help to establish more efficient cell culture models for HCV using
      alternative isolates.

PMID- 19740983
TI  - The roles of chemokines in rabies virus infection: overexpression may not always
      be beneficial.
AB  - It was found previously that induction of innate immunity, particularly
      chemokines, is an important mechanism of rabies virus (RABV) attenuation. To
      evaluate the effect of overexpression of chemokines on RABV infection, chemokines
      macrophage inflammatory protein 1alpha (MIP-1alpha), RANTES, and IP-10 were
      individually cloned into the genome of attenuated RABV strain HEP-Flury. These
      recombinant RABVs were characterized in vitro for growth properties and
      expression of chemokines. It was found that all the recombinant viruses grew as
      well as the parent virus, and each of the viruses expressed the intended
      chemokine in a dose-dependent manner. When these viruses were evaluated for
      pathogenicity in the mouse model, it was found that overexpression of MIP-1alpha
      further decreased RABV pathogenicity by inducing a transient innate immune
      response. In contrast, overexpression of RANTES or IP-10 increased RABV
      pathogenicity by causing neurological diseases, which is due to persistent and
      high-level expression of chemokines, excessive infiltration and accumulation of
      inflammatory cells in the central nervous system, and severe enhancement of blood
      brain barrier permeability. These studies indicate that overexpression of
      chemokines, although important in controlling virus infection, may not always be
      beneficial to the host.

PMID- 19740984
TI  - Tryptophan residues in the portal protein of herpes simplex virus 1 critical to
      the interaction with scaffold proteins and incorporation of the portal into
      capsids.
AB  - Incorporation of the herpes simplex virus 1 (HSV-1) portal vertex into the capsid
      requires interaction with a 12-amino-acid hydrophobic domain within capsid
      scaffold proteins. The goal of this work was to identify domains and residues in
      the UL6-encoded portal protein pUL6 critical to the interaction with scaffold
      proteins. We show that whereas the wild-type portal and scaffold proteins readily
      coimmunoprecipitated with one another in the absence of other viral proteins,
      truncation beyond the first 18 or last 36 amino acids of the portal protein
      precluded this coimmunoprecipitation. The coimmunoprecipitation was also
      precluded by mutation of conserved tryptophan (W) residues to alanine (A) at
      positions 27, 90, 127, 163, 241, 262, 532, and 596 of UL6. All of these W-to-A
      mutations precluded the rescue of a viral deletion mutant lacking UL6, except
      W163A, which supported replication poorly, and W596A, which fully rescued
      replication. A recombinant virus bearing the W596A mutation replicated and
      packaged DNA normally, and scaffold proteins readily coimmunoprecipitated with
      portal protein from lysates of infected cells. Thus, viral functions compensated
      for the W596A mutation's detrimental effects on the portal-scaffold interaction
      seen during transient expression of portal and scaffold proteins. In contrast,
      the W27A mutation precluded portal-scaffold interactions in infected cell
      lysates, reduced the solubility of pUL6, decreased incorporation of the portal
      into capsids, and abrogated viral-DNA cleavage and packaging.

PMID- 19740985
TI  - Human papillomavirus (HPV) type 18 induces extended growth in primary human
      cervical, tonsillar, or foreskin keratinocytes more effectively than other high
      risk mucosal HPVs.
AB  - Mucosal high-risk (HR) human papillomaviruses (HPVs) that cause cervical and
      other anogenital cancers also are found in approximately 25% of head and neck
      carcinomas (HNCs), especially those arising in the oropharynx and the tonsils.
      While many HR HPV types are common in anogenital cancer, over 90% of HPV-positive
      HNCs harbor HPV type 16 (HPV-16). Using a quantitative colony-forming assay, we
      compared the ability of full-length mucosal HPV genomes, i.e., the low-risk HPV
      11 and HR HPV-16, -18, and -31, to persist in and alter the growth of primary
      human keratinocytes from the foreskin, cervix, and tonsils. The HR HPV types led
      to the formation of growing keratinocyte colonies in culture independent of the
      site of epithelial origin. However, HPV-18 induced colony growth in all
      keratinocytes >4-fold more effectively than HPV-16 or HPV-31 and >20-fold more
      efficiently than HPV-11 or controls. HPV-11-transfected or control colonies
      failed to expand beyond 32 to 36 population doublings postexplantation. In
      contrast, individual HR HPV-transfected clones exhibited no apparent slowdown of
      growth or "crisis," and many maintained HPV plasmid persistence beyond 60
      population doublings. Keratinocyte clones harboring extrachromosomal HR HPV
      genomes had shorter population doubling times and formed dysplastic stratified
      epithelia in organotypic raft cultures, mirroring the pathological features of
      higher-grade intraepithelial lesions, yet did not exhibit chromosomal
      instability. We conclude that, in culture, the HR HPV type, rather than the site
      of epithelial origin of the cells, determines the efficacy of inducing continued
      growth of individual keratinocytes, with HPV-18 being the most aggressive mucosal
      HR HPV type tested.

PMID- 19740986
TI  - GBF1, a guanine nucleotide exchange factor for Arf, is crucial for coxsackievirus
      B3 RNA replication.
AB  - The replication of enteroviruses is sensitive to brefeldin A (BFA), an inhibitor
      of endoplasmic reticulum-to-Golgi network transport that blocks activation of
      guanine exchange factors (GEFs) of the Arf GTPases. Mammalian cells contain three
      BFA-sensitive Arf GEFs: GBF1, BIG1, and BIG2. Here, we show that coxsackievirus
      B3 (CVB3) RNA replication is insensitive to BFA in MDCK cells, which contain a
      BFA-resistant GBF1 due to mutation M832L. Further evidence for a critical role of
      GBF1 stems from the observations that viral RNA replication is inhibited upon
      knockdown of GBF1 by RNA interference and that replication in the presence of BFA
      is rescued upon overexpression of active, but not inactive, GBF1. Overexpression
      of Arf proteins or Rab1B, a GTPase that induces GBF1 recruitment to membranes,
      failed to rescue RNA replication in the presence of BFA. Additionally, the
      importance of the interaction between enterovirus protein 3A and GBF1 for viral
      RNA replication was investigated. For this, the rescue from BFA inhibition of
      wild-type (wt) replicons and that of mutant replicons of both CVB3 and poliovirus
      (PV) carrying a 3A protein that is impaired in binding GBF1 were compared. The
      BFA-resistant GBF1-M832L protein efficiently rescued RNA replication of both wt
      and mutant CVB3 and PV replicons in the presence of BFA. However, another BFA
      resistant GBF1 protein, GBF1-A795E, also efficiently rescued RNA replication of
      the wt replicons, but not that of mutant replicons, in the presence of BFA. In
      conclusion, this study identifies a critical role for GBF1 in CVB3 RNA
      replication, but the importance of the 3A-GBF1 interaction requires further
      study.

PMID- 19740987
TI  - The first transmembrane domain of the hepatitis B virus large envelope protein is
      crucial for infectivity.
AB  - The early steps of the hepatitis B virus (HBV) life cycle are still poorly
      understood. Indeed, neither the virus receptor at the cell surface nor the
      mechanism by which nucleocapsids are delivered to the cytosol of infected cells
      has been identified. Extensive mutagenesis studies in pre-S1, pre-S2, and most of
      the S domain of envelope proteins revealed the presence of two regions essential
      for HBV infectivity: the 77 first residues of the pre-S1 domain and a
      conformational motif in the antigenic loop of the S domain. In addition, at the N
      terminal extremity of the S domain, a putative fusion peptide, partially
      overlapping the first transmembrane (TM1) domain and preceded by a PEST sequence
      likely containing several proteolytic cleavage sites, was identified. Since no
      mutational analysis of these two motifs potentially implicated in the fusion
      process was performed, we decided to investigate the ability of viruses bearing
      contiguous deletions or substitutions in the putative fusion peptide and PEST
      sequence to infect HepaRG cells. By introducing the mutations either in the L and
      M proteins or in the S protein, we demonstrated the following: (i) that in the
      TM1 domain of the L protein, three hydrophobic clusters of four residues were
      necessary for infectivity; (ii) that the same clusters were critical for S
      protein expression; and, finally, (iii) that the PEST sequence was dispensable
      for both assembly and infection processes.

PMID- 19740988
TI  - Expansion, reexpansion, and recall-like expansion of Vgamma2Vdelta2 T cells in
      smallpox vaccination and monkeypox virus infection.
AB  - Little is known about the in vivo kinetics of T-cell responses in
      smallpox/monkeypox. We showed that macaque Vgamma2Vdelta2 T cells underwent 3
      week-long expansion after smallpox vaccine immunization and displayed simple
      reexpansion in association with sterile anti-monkeypox virus (anti-MPV) immunity
      after MPV challenge. Virus-activated Vgamma2Vdelta2 T cells exhibited gamma
      interferon-producing effector function after phosphoantigen stimulation.
      Surprisingly, like alphabeta T cells, suboptimally primed Vgamma2Vdelta2 T cells
      in vaccinia virus/cidofovir-covaccinated macaques mounted major recall-like
      expansion after MPV challenge. Finally, Vgamma2Vdelta2 T cells localized in
      inflamed lung tissues for potential regulation. Our studies provide the first in
      vivo evidence that viruses, despite their inability to produce exogenous
      phosphoantigen, can induce expansion, reexpansion, and recall-like expansion of
      Vgamma2Vdelta2 T cells and stimulate their antimicrobial cytokine response.

PMID- 19740989
TI  - Role of RNA structures in genome terminal sequences of the hepatitis C virus for
      replication and assembly.
AB  - Hepatitis C virus (HCV) is a positive-strand RNA virus replicating its genome via
      a negative-strand [(-)] intermediate. Little is known about replication signals
      residing in the 3' end of HCV (-) RNA. Recent studies identified seven stem-loop
      structures (SL-I', -IIz', -IIy', -IIIa', -IIIb', -IIIcdef', and -IV') in this
      region. In the present study, we mapped the minimal region required for RNA
      replication to SL-I' and -IIz', functionally confirmed the SL-IIz' structure, and
      identified SL-IIIa' to -IV' as auxiliary replication elements. In addition, we
      show that the 5' nontranslated region of the genome most likely does not contain
      cis-acting RNA structures required for RNA packaging into infectious virions.

PMID- 19740990
TI  - Adult AIDS-like disease in a novel inducible human immunodeficiency virus type 1
      Nef transgenic mouse model: CD4+ T-cell activation is Nef dependent and can occur
      in the absence of lymphophenia.
AB  - CD4C/HIV(nef) transgenic (Tg) mice express Nef in CD4+ T cells and in the cells
      of the macrophage/monocyte/dendritic lineage, and they develop an AIDS-like
      disease similar to human AIDS. In these mice, Nef is constitutively expressed
      throughout life. To rule out the contribution of any developmental defects caused
      by early expression of Nef, we generated inducible human immunodeficiency virus
      type 1 (HIV-1) Nef Tg mice by using the tetracycline-inducible system. Faithful
      expression of the Nef transgene was induced in (CD4C/rtTA x TRE/HIV(Nef)) or
      (CD4C/rtTA2S-M2 x TRE/HIV(Nef)) double-Tg mice upon doxycycline (DOX) treatment
      in drinking water. Long-term treatment of these mice with DOX also led to loss,
      apoptosis, and activation of CD4+ T cells, this latter phenotype being observed
      even with low levels of Nef. These phenotypes could be transferred by bone marrow
      (BM) transplantation, indicating a hematopoietic cell autonomous effect. In
      addition, in mixed Tg:non-Tg BM chimeras, only Tg and not non-Tg CD4+ T cells
      exhibited an effector/memory phenotype in the absence of lymphopenia. Finally,
      the DOX-induced double-Tg mice developed nonlymphoid organ diseases similar to
      those of CD4C/HIV(Nef) Tg mice and of humans infected with HIV-1. These results
      show for the first time that adult mice are susceptible to the detrimental action
      of Nef and that Nef-mediated T-cell activation can be independent of lymphopenia.
      These Tg mice represent a unique model which is likely to be instrumental for
      understanding the cellular and molecular pathways of Nef action as well as the
      main characteristics of immune reconstitution following DOX withdrawal.

PMID- 19740992
TI  - Semliki forest virus expressing interleukin-12 induces antiviral and antitumoral
      responses in woodchucks with chronic viral hepatitis and hepatocellular
      carcinoma.
AB  - A vector based on Semliki Forest virus (SFV) expressing high levels of
      interleukin-12 (SFV-enhIL-12) has previously demonstrated potent antitumoral
      efficacy in small rodents with hepatocellular carcinoma (HCC) induced by
      transplantation of tumor cells. In the present study, the infectivity and
      antitumoral/antiviral effects of SFV vectors were evaluated in the clinically
      more relevant woodchuck model, in which primary HCC is induced by chronic
      infection with woodchuck hepatitis virus (WHV). Intratumoral injection of SFV
      vectors expressing luciferase or IL-12 resulted in high reporter gene activity
      within tumors and cytokine secretion into serum, respectively, demonstrating that
      SFV vectors infect woodchuck tumor cells. For evaluating antitumoral efficacy,
      woodchuck tumors were injected with increasing doses of SFV-enhIL-12, and tumor
      size was measured by ultrasonography following treatment. In five (83%) of six
      woodchucks, a dose-dependent, partial tumor remission was observed, with
      reductions in tumor volume of up to 80%, but tumor growth was restored
      thereafter. Intratumoral treatment further produced transient changes in WHV
      viremia and antigenemia, with >or=1.5-log(10) reductions in serum WHV DNA in half
      of the woodchucks. Antitumoral and antiviral effects were associated with T-cell
      responses to tumor and WHV antigens and with expression of CD4 and CD8 markers,
      gamma interferon, and tumor necrosis factor alpha in peripheral blood mononuclear
      cells, suggesting that immune responses against WHV and HCC had been induced.
      These experimental observations suggest that intratumoral administration of SFV
      enhIL-12 may represent a strategy for treatment of chronic HBV infection and
      associated HCC in humans but indicate that this approach could benefit from
      further improvements.

PMID- 19740993
TI  - Akt inhibitor Akt-IV blocks virus replication through an Akt-independent
      mechanism.
AB  - Many viruses activate the phosphatidylinositol 3'-kinase (PI3k)/Akt intracellular
      signaling pathway to promote viral replication. We have analyzed whether a
      rapidly replicating rhabdovirus, vesicular stomatitis virus (VSV), requires the
      PI3k/Akt signaling pathway for its replication. Through the use of chemical
      inhibitors of PI3k and Akt, we show that VSV replication and cytopathic effects
      do not require activation of these kinases. Inhibitors that block the activating
      phosphorylations of Akt at threonine 308 (Thr308) and serine 473 (Ser473) did not
      inhibit VSV protein expression or the induction of the cytopathic effects of VSV.
      One compound, Akt inhibitor Akt-IV, inhibited the replication of VSV, respiratory
      syncytial virus, and vaccinia virus but increased the phosphorylation of Akt at
      positions Thr308 and Ser473 and did not inhibit Akt kinase activity in vitro.
      Together, our data suggest that the PI3k/Akt pathway is of limited relevance to
      the replication of VSV but that Akt inhibitor Akt-IV is a novel broad-spectrum
      antiviral compound with a mechanism differing from that of its previously
      reported effect on the PI3k/Akt pathway. Identification of other targets for this
      compound may define a new approach for blocking virus replication.

PMID- 19740991
TI  - Full-length characterization of hepatitis C virus subtype 3a reveals novel
      hypervariable regions under positive selection during acute infection.
AB  - Hepatitis C virus subtype 3a is a highly prevalent and globally distributed
      strain that is often associated with infection via injection drug use. This
      subtype exhibits particular phenotypic characteristics. In spite of this,
      detailed genetic analysis of this subtype has rarely been performed. We performed
      full-length viral sequence analysis in 18 patients with chronic HCV subtype 3a
      infection and assessed genomic viral variability in comparison to other HCV
      subtypes. Two novel regions of intragenotypic hypervariability within the
      envelope protein E2, of HCV genotype 3a, were identified. We named these regions
      HVR495 and HVR575. They consisted of flanking conserved hydrophobic amino acids
      and central variable residues. A 5-amino-acid insertion found only in genotype 3a
      and a putative glycosylation site is contained within HVR575. Evolutionary
      analysis of E2 showed that positively selected sites within genotype 3a infection
      were largely restricted to HVR1, HVR495, and HVR575. Further analysis of clonal
      viral populations within single hosts showed that viral variation within HVR495
      and HVR575 were subject to intrahost positive selecting forces. Longitudinal
      analysis of four patients with acute HCV subtype 3a infection sampled at multiple
      time points showed that positively selected mutations within HVR495 and HVR575
      arose early during primary infection. HVR495 and HVR575 were not present in HCV
      subtypes 1a, 1b, 2a, or 6a. Some variability that was not subject to positive
      selection was present in subtype 4a HVR575. Further defining the functional
      significance of these regions may have important implications for genotype 3a E2
      virus-receptor interactions and for vaccine studies that aim to induce cross
      reactive anti-E2 antibodies.

PMID- 19740994
TI  - Inhibition of human cytomegalovirus replication via peptide aptamers directed
      against the nonconventional nuclear localization signal of the essential viral
      replication factor pUL84.
AB  - The UL84 open reading frame of human cytomegalovirus encodes an essential
      multifunctional regulatory protein that is thought to act in the nucleus as an
      initiator of lytic viral replication. Nuclear trafficking of pUL84 is facilitated
      by a complex nonconventional nuclear localization signal (NLS) that mediates its
      interaction with the cellular importin-alpha/beta pathway. Since binding of pUL84
      to importin-alpha proteins mechanistically differs from that of cellular proteins
      containing a classical NLS, we assumed that specific interference with the
      nuclear import of pUL84 might be possible and that this could constitute a novel
      principle for antiviral therapy. In order to test this hypothesis, we employed
      peptide aptamer technology and isolated several peptide aptamers from a
      randomized peptide expression library that specifically bind with high affinity
      to the unconventional pUL84 NLS under intracellular conditions.
      Coimmunoprecipitation experiments confirmed these interactions in mammalian
      cells, and the antiviral potential of the identified peptide aptamers was
      determined using three independent experimental approaches. (i) Infection
      experiments with a recombinant human cytomegalovirus expressing green fluorescent
      protein demonstrated 50 to 60% decreased viral replication in primary human
      fibroblasts stably expressing pUL84-specific aptamers. (ii) A 50 to 70% reduction
      of viral plaque formation, as well as a 70 to 90% inhibition of virus release in
      the presence of pUL84-specific aptamers, was observed. (iii) Immunofluorescence
      analyses revealed a shift from an almost exclusively nuclear pUL84 staining
      pattern to a nucleocytoplasmic distribution upon coexpression of the identified
      molecules, indicating that interference with the nuclear import of pUL84
      contributes to the observed antiviral activity of the identified pUL84-binding
      aptamer molecules.

PMID- 19740995
TI  - Why do phage play dice?
AB  - Phage lambda is among the simplest organisms that make a developmental decision.
      An infected bacterium goes either into the lytic state, where the phage particles
      rapidly replicate and eventually lyse the cell, or into a lysogenic state, where
      the phage goes dormant and replicates along with the cell. Experimental
      observations by P. Kourilsky are consistent with a single phage infection
      deterministically choosing lysis and double infection resulting in a stochastic
      choice. We argue that the phage are playing a "game" of minimizing the chance of
      extinction and that the shift from determinism to stochasticity is due to a shift
      from a single-player to a multiplayer game. Crucial to the argument is the clonal
      identity of the phage.

PMID- 19740996
TI  - Protective role of Fas-FasL signaling in lethal infection with herpes simplex
      virus type 2 in mice.
AB  - Herpes simplex virus type 2 (HSV-2) induces acute local infection followed by
      latent infection in the nervous system and often leads to the development of
      lethal encephalitis in immunocompromised hosts. The mechanisms of immune
      protection against lethal HSV-2 infection, however, have not been clarified. In
      this study, we examined the roles of Fas-Fas ligand (FasL) signaling in lethal
      infection with HSV-2 by using mice with mutated Fas (lpr) or FasL (gld) in
      C57BL/6 background. Both lpr and gld mice exhibited higher mortality than wild
      type (WT) C57BL/6 mice after infection with virulent HSV-2 strain 186 and showed
      significantly increased viral titers in the spinal cord compared with WT mice 9
      days after infection, just before the mice started to die. There were no
      differences in the numbers of CD4+ and CD8+ T cells infiltrated in the spinal
      cord or in the levels of HSV-2-specific gamma interferon produced by those cells
      in a comparison of lpr and WT mice 9 days after infection. Adoptive transfer
      studies demonstrated that CD4+ T cells from WT mice protected gld mice from
      lethal infection by HSV-2. Furthermore, CD4+ T cells infiltrated in the spinal
      cord of HSV-2-infected WT mice expressed functional FasL that induced apoptosis
      of Fas-expressing target cells in vitro. These results suggest that FasL-mediated
      cytotoxic activity of CD4+ T cells plays an important role in host defense
      against lethal infection with HSV-2.

PMID- 19740997
TI  - Long-term administration of valacyclovir reduces the number of Epstein-Barr virus
      (EBV)-infected B cells but not the number of EBV DNA copies per B cell in healthy
      volunteers.
AB  - Epstein-Barr virus (EBV) establishes a latent infection in B cells in the blood,
      and the latent EBV load in healthy individuals is generally stable over time,
      maintaining a "set point." It is unknown if the EBV load changes after long-term
      antiviral therapy in healthy individuals. We treated volunteers with either
      valacyclovir (valaciclovir) or no antiviral therapy for 1 year and measured the
      amount of EBV DNA in B cells every 3 months with a novel, highly sensitive assay.
      The number of EBV-infected B cells decreased in subjects receiving valacyclovir
      (half-life of 11 months; P = 0.02) but not in controls (half-life of 31 years; P
      = 0.86). The difference in the slopes of the lines for the number of EBV-infected
      B cells over time for the valacyclovir group versus the control group approached
      significance (P = 0.054). In contrast, the number of EBV DNA copies per B cell
      remained unchanged in both groups (P = 0.62 and P = 0.92 for the control and
      valacyclovir groups, respectively). Valacyclovir reduces the frequency of EBV
      infected B cells when administered over a long period and, in theory, might allow
      eradication of EBV from the body if reinfection does not occur.

PMID- 19740998
TI  - Cleavage of IPS-1 in cells infected with human rhinovirus.
AB  - Rhinoviruses are prevalent human pathogens that are associated with life
      threatening acute asthma exacerbations. The innate immune response to rhinovirus
      infection, which may play an important role in virus-induced asthma induction,
      has not been comprehensively investigated. We examined the innate immune response
      in cells infected with human rhinovirus 1a (HRV1a). Beta interferon (IFN-beta)
      mRNA was induced in HRV1a-infected cells at levels significantly lower than in
      cells infected with Sendai virus. To understand the basis for this observation,
      we determined whether components of the pathway leading to IFN-beta induction
      were altered during infection. Dimerization of the transcription factor IRF-3,
      which is required for synthesis of IFN-beta mRNA, is not observed in cells
      infected with HRV1a. Beginning at 7 h postinfection, IPS-1, a protein that is
      essential for cytosolic sensing of viral RNA, is degraded in HRV1a-infected
      cells. Induction of apoptosis by puromycin led to the cleavage of IPS-1, but
      treatment of HRV1a-infected cells with the pan-caspase inhibitor, zVAD, did not
      block cleavage of IPS-1. IPS-1 is cleaved in vitro by caspase-3 and by the
      picornaviral proteinases 2A(pro) and 3C(pro). Expression of HRV1a and polioviral
      2A(pro) and 3C(pro) led to degradation of IPS-1 in cells. These results suggest
      that IPS-1 is cleaved during HRV1a infection by three different proteases.
      Cleavage of IPS-1 may be a mechanism for evasion of the type I IFN response,
      leading to a more robust infection.

PMID- 19740999
TI  - Differences in the regulatory and functional effects of the Us3 protein kinase
      activities of herpes simplex virus 1 and 2.
AB  - Us3 protein kinases encoded by herpes simplex virus 1 (HSV-1) and 2 (HSV-2) are
      serine/threonine protein kinases and play critical roles in viral replication and
      pathogenicity in vivo. In the present study, we investigated differences in the
      biological properties of HSV-1 and HSV-2 Us3 protein kinases and demonstrated
      that HSV-2 Us3 did not have some of the HSV-1 Us3 kinase functions, including
      control of nuclear egress of nucleocapsids, localization of UL31 and UL34, and
      cell surface expression of viral envelope glycoprotein B. In agreement with the
      observations that HSV-2 Us3 was less important for these functions, the effect of
      HSV-2 Us3 kinase activity on virulence in mice following intracerebral
      inoculation was much lower than that of HSV-1 Us3. Furthermore, we showed that
      alanine substitution in HSV-2 Us3 at a site (aspartic acid at position 147)
      corresponding to one that can be autophosphorylated in HSV-1 Us3 abolished HSV-2
      Us3 kinase activity. Thus, the regulatory and functional effects of Us3 kinase
      activity are different between HSV-1 and HSV-2.

PMID- 19741000
TI  - Human endogenous retroviral long terminal repeat sequences as cell type-specific
      promoters in retroviral vectors.
AB  - The human genome contains more than half a million human endogenous retrovirus
      (HERV) long terminal repeats (LTRs) that can be regarded as mobile regulatory
      modules. Many of these HERV LTRs have been recruited during evolution as
      transcriptional control elements for cellular gene expression. We have cloned LTR
      sequences from two HERV families, HERV-H and HERV-L, differing widely in their
      activity and tissue specificity into a murine leukemia virus (MLV)-based promoter
      conversion vector (ProCon). Various human cell lines were infected with the HERV
      MLV hybrid vectors, and cell type-specific expression of the reporter gene was
      compared with the promoter specificity of the corresponding HERV LTRs in
      transient-transfection assays. Transcription start site analysis of HERV-MLV
      hybrid vectors revealed preferential use of the HERV promoter initiation site.
      Our data show that HERV LTRs function in the context of retroviral vectors in
      certain cell types and have the potential to be useful as cell type-specific
      promoters in vector construction.

PMID- 19741002
TI  - The 'trade-off' between synthesis of primary and secondary compounds in young
      tomato leaves is altered by nitrate nutrition: experimental evidence and model
      consistency.
AB  - Plants allocate internal resources to fulfil essential, yet possibly conflicting,
      demands such as defence or growth, as hypothesized by the 'growth-differentiation
      balance theory' (GDB). This trade-off was examined in young tomato plants grown
      for 25 d using the nutrient film technique with seven nitrate concentrations
      ([NO(3)]). The modification of primary (growth-related: organic acids,
      carbohydrates) and secondary (defence-related: phenolics) metabolite
      concentrations in leaves was assessed. Then a simple model was devised to
      simulate the trade-off between growth and secondary metabolism in response to N
      nutrition. N affected growth and metabolite concentrations in the leaves. Dry
      biomass, leaf area, and concentrations of nitrate and organic acid (malic,
      citric) increased with rising [NO(3)], up to a threshold, above which they
      remained constant. Starch, sucrose, and organic N concentrations were invariant
      with [NO(3)]. Glucose, fructose, and phenolic (chlorogenic acid, rutin, and
      kaempferol-rutinoside) concentrations were highest at lowest [NO(3)]. They
      declined progressively with rising [NO(3)] until a threshold, above which they
      remained constant. Model predictions are in phase with experimental phenolic
      concentration data although the simulated metabolic rates differ from the GDBH
      proposals depicted in the literature. From the model output it is shown that a
      careful definition of the C reserve compounds is required.

PMID- 19741001
TI  - The endoplasmic reticulum chaperone BiP/GRP78 is important in the structure and
      function of the human cytomegalovirus assembly compartment.
AB  - We previously demonstrated that the endoplasmic reticulum (ER) chaperone BiP
      functions in human cytomegalovirus (HCMV) assembly and egress. Here, we show that
      BiP localizes in two cytoplasmic structures in infected cells. Antibodies to the
      extreme C terminus, which includes BiP's KDEL ER localization sequence, detect
      BiP in regions of condensed ER near the periphery of the cell. Antibodies to the
      full length, N terminus, or larger portion of the C terminus detect BiP in the
      assembly compartment. This inability of C-terminal antibodies to detect BiP in
      the assembly compartment suggests that BiP's KDEL sequence is occluded in the
      assembly compartment. Depletion of BiP causes the condensed ER and assembly
      compartments to dissociate, indicating that BiP is important for their integrity.
      BiP and pp28 are in association in the assembly compartment, since antibodies
      that detect BiP in the assembly compartment coimmunoprecipitate pp28 and vice
      versa. In addition, BiP and pp28 copurify with other assembly compartment
      components on sucrose gradients. BiP also coimmunoprecipitates TRS1. Previous
      data show that cells infected with a TRS1-deficient virus have cytoplasmic and
      assembly compartment defects like those seen when BiP is depleted. We show that a
      fraction of TRS1 purifies with the assembly compartment. These findings suggest
      that BiP and TRS1 share a function in assembly compartment maintenance. In
      summary, BiP is diverted from the ER to associate with pp28 and TRS1,
      contributing to the integrity and function of the assembly compartment.

PMID- 19741003
TI  - Keeping Kids Smokefree: lessons learned on community participation.
AB  - Community participation in program decision-making and implementation is an ideal
      that community and academic stakeholders aspire to in participatory research.
      This ideal, however, can be difficult to achieve. We describe lessons learned
      about community participation from a quasi-experimental trial aimed at reducing
      the uptake of smoking among pre-adolescents in a community with a high percentage
      of Maori and Pacific Island people. The intervention involves students, parents,
      school teachers and management, extended families and members of the wider
      community. A total of approximately 4000 students (and their parents) of four
      urban Auckland schools were enrolled in the study over 3 years. The intervention
      is carried out through collaborations between public health professionals,
      academic institutions and school personnel. In order to enhance community
      participation, we conclude that (i) time commitment is needed to establish long
      term ongoing relationships through face-to-face communication, (ii) research team
      members should ideally share similar cultural and ethnic backgrounds to the
      target audience and have in-depth understanding of and experience in the
      community milieu and (iii) collaborative partnerships between academic
      institutions and public health services are necessary to create strength and
      cohesion, and assist with clear articulation of the research project mission and
      objectives.

PMID- 19741004
TI  - Lineage-specific adaptive evolution of the centromeric protein CENH3 in diploid
      and allotetraploid Oryza species.
AB  - Centromeres in eukaryotic species are defined by the presence of a centromere
      specific histone H3 variant, CENH3. CENH3 plays a key role in recruiting other
      centromeric proteins; thus, it is the central component in kinetochore formation
      and centromere function. The CENH3 proteins in several plant and animal species
      were found to be under positive selection, which was hypothesized to respond to
      the rapid changing of the repetitive DNA sequences associated with the
      centromeres. Here, we report the expression and evolution of the CenH3 genes in
      two allotetraploid rice species as well as their representative diploid
      progenitor species. Both copies of the CenH3 genes were transcribed in the two
      allotetraploid species and showed a nonpreferential expression pattern.
      Contrasting positive and stabilizing selection of the CenH3 genes was associated
      with different diploid Oryza species. This lineage-specific adaptive evolution of
      CENH3 was maintained in the two allotetraploid species. Thus, we demonstrate that
      the allopolyploidization events did not alter the expression or evolutionary
      patterns of the CenH3 genes in the Oryza species.

PMID- 19741005
TI  - beta-Arrestin-2 interaction and internalization of the human P2Y1 receptor are
      dependent on C-terminal phosphorylation sites.
AB  - The nucleotide receptor P2Y(1) regulates a variety of physiological processes and
      is involved in platelet aggregation. Using human P2Y(1)-receptors C-terminally
      fused with a fluorescent protein, we studied the role of potential receptor
      phosphorylation sites in receptor internalization and beta-arrestin-2
      translocation by means of confocal microscopy. Three receptor constructs were
      generated that lacked potential phosphorylation sites in the third intracellular
      loop, the proximal C terminus, or the distal C terminus. The corresponding
      receptor constructs were expressed in human embryonic kidney (HEK)-293 cells and
      stimulated with 100 muM ADP. Rapid receptor internalization was observed for the
      wild-type receptor and from those constructs mutated in the third intracellular
      loop and the proximal C terminus. However, the construct lacking phosphorylation
      sites at the distal C terminus did not show receptor internalization upon
      stimulation. The microscopic data were validated by HA-tagged receptor constructs
      using a cell surface enzyme-linked immunosorbent assay. P2Y(1)-receptor
      stimulated beta-arrestin-2-yellow fluorescent protein (YFP) translocation
      followed the same pattern as receptor internalization. Hence, no beta-arrestin-2
      YFP translocation was observed when the distal C-terminal phosphorylation sites
      were mutated. Individual mutations indicate that residues Ser352 and Thr358 are
      essential for receptor internalization and beta-arrestin-2-YFP translocation. In
      contrast, protein kinase C (PKC)-mediated receptor desensitization was not
      affected by mutation of potential phosphorylation sites in the distal C terminus
      but was prevented by mutation of potential phosphorylation sites in the proximal
      C terminus. P2Y(1)-receptor internalization in HEK-293 cells was not blocked by
      inhibitors of PKC and calmodulin-dependent protein kinase. Thus, we conclude that
      P2Y(1)-receptor desensitization and internalization are mediated by different
      phosphorylation sites and kinases.

PMID- 19741006
TI  - KU135, a novel novobiocin-derived C-terminal inhibitor of the 90-kDa heat shock
      protein, exerts potent antiproliferative effects in human leukemic cells.
AB  - The 90-kDa heat shock protein (Hsp90) assists in the proper folding of numerous
      mutated or overexpressed signal transduction proteins that are involved in
      cancer. Consequently, there is considerable interest in developing
      chemotherapeutic drugs that specifically disrupt the function of Hsp90. Here, we
      investigated the extent to which a novel novobiocin-derived C-terminal Hsp90
      inhibitor, designated KU135, induced antiproliferative effects in Jurkat T
      lymphocytes. The results indicated that KU135 bound directly to Hsp90, caused the
      degradation of known Hsp90 client proteins, and induced more potent
      antiproliferative effects than the established N-terminal Hsp90 inhibitor 17
      allylamino-demethoxygeldanamycin (17-AAG). Closer examination of the cellular
      response to KU135 and 17-AAG revealed that only 17-AAG induced a strong up
      regulation of Hsp70 and Hsp90. In addition, KU135 caused wild-type cells to
      undergo G(2)/M arrest, whereas cells treated with 17-AAG accumulated in G(1).
      Furthermore, KU135 but not 17-AAG was found to be a potent inducer of
      mitochondria-mediated apoptosis as evidenced, in part, by the fact that cell
      death was inhibited to a similar extent by Bcl-2/Bcl-x(L) overexpression or the
      depletion of apoptotic protease-activating factor-1 (Apaf-1). Together, these
      data suggest that KU135 inhibits cell proliferation by regulating signaling
      pathways that are mechanistically different from those targeted by 17-AAG and as
      such represents a novel opportunity for Hsp90 inhibition.

PMID- 19741007
TI  - Regulation of serotonin 1B receptor by glycogen synthase kinase-3.
AB  - In response to 5-hydroxytryptamine (5-HT), the type 1 serotonin receptors (5
      HT1Rs) preferentially couple to the inhibitory G protein and elicit many
      physiological and behavioral processes. However, their regulation by
      intracellular protein kinases has not been fully investigated. In this study, we
      identified that glycogen synthase kinase-3 (GSK3) differentially regulates 5
      HT1Rs. In receptor-expressing cells and brain slices, activation of both 5-HT1AR
      and 5-HT1BR reduced forskolin-stimulated cAMP production, but only the effect of
      5-HT1BR was abolished by selective GSK3 inhibitors, deletion of GSK3beta by RNAi,
      or overexpression of impaired GSK3beta mutants (R96A and K85,86A). A consensus
      GSK3 phosphorylation sequence was identified between the serine-154 and threonine
      158 in the second intracellular loop of 5-HT1BR. Mutation of either serine-154 or
      threonine-158 to alanine significantly reduced response of 5-HT1BR to 5-HT.
      Active GSK3beta interacted with resting 5-HT1BR to form a protein complex. The
      interaction was enhanced by receptor activation, abolished by GSK3 inhibitors,
      and dependent on the phosphorylation state of serine-154. In addition, regulation
      of 5-HT1BR by GSK3 changed the dynamics of agonist-induced cell surface receptor
      internalization, in which lack of phosphorylation at Ser154 resulted in sustained
      reduction of 5-HT1BR at the cell surface. Although the physiological consequences
      of selective regulation of 5-HT1BR by GSK3 remain to be identified, findings in
      this study reveal a new function of GSK3 as a protein kinase that is able to
      selectively regulate G protein-coupled receptors.

PMID- 19741009
TI  - Fast microvascular remodelling in a patient with cancer-associated
      dermatomyositis: capillaroscopic follow-up.

PMID- 19741010
TI  - A strong heritability of psoriatic arthritis over four generations--the Reykjavik
      Psoriatic Arthritis Study.
AB  - OBJECTIVE: We have studied the prevalence of PsA in Reykjavik, Iceland, in a
      population-based cohort, and using the Icelandic genealogy database we have
      estimated the risk ratio (RR) spanning five generations. METHODS: The national
      identification numbers of all 220 living Icelanders in Reykjavik known to have
      PsA were linked with the genealogy database. RRs for developing PsA were
      estimated in first-degree relatives (FDRs) to fifth-degree relatives of PsA
      cases. The kinship coefficient (KC) for PsA was also calculated. The control
      populations were 1000 and 10,000 sets of matched Icelandic subjects for each
      proband, respectively. RESULTS: FDRs to fourth-degree relatives of patients with
      PsA had RRs of 39, 12, 3.6 and 2.3, respectively (all P-values < 0.0001),
      reflecting a strong genetic component, whereas the fifth-degree relatives had an
      RR of 1.2 (P = 0.236). KCs of 5.0, 3.4, 1.7, 1.3, 1.0, 0.8 and 0.7 were observed
      for the first seven excluded meioses (all P-values < 0.0001), confirming the
      familial risk. CONCLUSIONS: Patients with PsA in Reykjavik, Iceland, are
      significantly more related to each other than to randomly sampled control
      subjects. This is in agreement with previous reports, but the present study
      examines the inheritance in more distantly related individuals. These findings
      indicate that in addition to a strong and complex genetic component in PsA, there
      is an important environmental contribution.

PMID- 19741008
TI  - Investigating the viability of genetic screening/testing for RA susceptibility
      using combinations of five confirmed risk loci.
AB  - OBJECTIVE: Five loci-the shared epitope (SE) of HLA--DRB1, the PTPN22 gene, a
      locus on 6q23, the STAT4 gene and a locus mapping to the TRAF1/C5 genetic region-
      have now been unequivocally confirmed as conferring susceptibility to RA. The
      largest single effect is conferred by SE. We hypothesized that combinations of
      susceptibility alleles may increase risk over and above that of any individual
      locus alone. METHODS: We analysed data from 4238 RA cases and 1811 controls, for
      which genotypes were available at all five loci. RESULTS: Statistical analysis
      identified eight high-risk combinations conferring an odds ratio >6 compared with
      carriage of no susceptibility variants and, interestingly, 10% population
      controls carried a combination conferring high risk. All high-risk combinations
      included SE, and all but one contained PTPN22. Statistical modelling showed that
      a model containing only these two loci could achieve comparable sensitivity and
      specificity to a model including all five. Furthermore, replacing SE (which
      requires full subtyping at the HLA-DRB1 gene) with DRB1*1/4/10 carriage resulted
      in little further loss of information (correlation coefficient between models =
      0.93). CONCLUSIONS: This represents the first exploration of the viability of
      population screening for RA and identifies several high-risk genetic
      combinations. However, given the population incidence of RA, genetic screening
      based on these loci alone is neither sufficiently sensitive nor specific at the
      current time.

PMID- 19741011
TI  - Evaluation of two strategies (initial methotrexate monotherapy vs its combination
      with adalimumab) in management of early active rheumatoid arthritis: data from
      the GUEPARD trial.
AB  - OBJECTIVES: In early and active RA despite MTX, continuous treatment with TNF
      blockers in combination with MTX is recommended. To compare this strategy with an
      initial combination of MTX and adalimumab (ADA) given for 3 months and then
      adjusted based on the disease activity status. METHODS: Prospective unblinded
      randomized multicentre controlled 1-year trial in which 65 patients with early
      (<6 months) and active [disease activity score (DAS28(ESR)) >5.1] RA were
      assigned to Group 1 (32 patients): MTX (0.3 mg/kg/week, maximum of 20 mg/week,
      without escalating dose regimen) or to Group 2 (33 patients): initial combination
      therapy with MTX (as in Group 1) and ADA (40 mg eow). In both groups, treatment
      was adjusted every 3 months. The aim was to achieve a low DAS (DAS28(ESR) <3.2).
      RESULTS: From Week 12 until Week 52, seven patients in Group 1 and 11 patients in
      Group 2 remained in low disease activity state while receiving MTX monotherapy (P
      = 0.28). The 1-year area under the curve (AUC) of DAS28 was lower in Group 2
      owing to an initial better response. The total intake of anti-TNF-alpha and the
      mean increase in total modified Sharp score was similar in the two groups.
      CONCLUSIONS: Initial combination of MTX and ADA and then an adjusted based on the
      disease activity status achieved a faster control of disease activity but did not
      increase the number of patients for whom anti-TNF-alpha treatment was not needed
      after 12 weeks nor a better subsequent clinical or radiological outcome than a 3
      month delayed initiation of anti-TNF in patients with still active disease
      despite MTX.

PMID- 19741012
TI  - Differential regulation of E-cadherin and alpha-smooth muscle actin by BMP 7 in
      human renal proximal tubule epithelial cells and its implication in renal
      fibrosis.
AB  - Chronic kidney diseases are characterized by progressive tubulointerstitial
      fibrosis, and TGFbeta1 plays a crucial role in its development. Bone morphogenic
      protein 7 (BMP 7), another member of the TGF superfamily, antagonized the
      profibrotic effects of TGFbeta1, including epithelial mesenchymal transition and
      E-cadherin loss, in the previous studies from animal models. We investigated the
      effect of BMP 7 on TGFbeta1-mediated E-cadherin loss in two different transformed
      human adult proximal tubule epithelia. We found that BMP 7 not only failed to
      prevent TGFbeta1-mediated E-cadherin loss but itself downregulated E-cadherin
      levels and that it had an additive effect with TGFbeta1 in inducing E-cadherin
      loss. The downregulation of E-cadherin by BMP 7 was mediated through the Smad1/5
      pathway. BMP 7-mediated E-cadherin loss was not followed by de novo alpha-smooth
      muscle actin (alpha-SMA) expression (a marker of myofibroblastic phenotype),
      which was due to the concurrent induction of Inhibitor of DNA binding 1 (Id1, a
      basic helix loop helix class transcriptional regulator) through a non-Smad
      pathway. Concurrent treatment of BMP 7 and TGFbeta1 prevented TGFbeta1-mediated
      alpha-SMA induction. In summary, our results suggest that E-cadherin loss, the
      key feature of epithelial mesenchymal transition, will not necessarily be
      followed by total phenotype change; rather, cells may undergo some loss of
      phenotypic marker in a ligand-dependent manner and participate in reparative
      processes. The inhibition of de novo expression of alpha-SMA could explain the
      antifibrotic effect of BMP 7. Id1 might play a crucial role in maintaining
      proximal tubule epithelial cell phenotype and its signaling regulation could be a
      potential therapeutic target.

PMID- 19741013
TI  - Purinoceptor regulation of renal tubular transport is coming of age.

PMID- 19741015
TI  - Surface expression of sodium channels and transporters in rat kidney: effects of
      dietary sodium.
AB  - The abundance of Na transport proteins in the luminal membrane of the rat kidney
      was assessed using in situ biotinylation and immunoblotting. When animals were
      fed an Na-deficient diet for 1 wk, the amounts of epithelial Na channel (ENaC)
      beta-subunit (beta-ENaC) and gamma-subunit (gamma-ENaC) and Na-Cl cotransporter
      (NCC) protein in the surface fraction increased relative to controls by 1.9-, 3.5
      , and 1.5-fold, respectively. The amounts of the luminal Na/H exchanger (NHE3)
      and the luminal Na-K-2Cl cotransporter (NKCC2) did not change significantly. The
      increases in ENaC subunits were mimicked by administration of aldosterone for 1
      wk, but the increase in NCC was not. When the animals were fed a high-Na (5%
      NaCl) diet for 1 wk, the surface expression of beta-ENaC increased by 50%,
      whereas that of the other membrane proteins did not change, relative to controls.
      The biochemical parameter most strongly affected by dietary Na was the abundance
      of the 65-kDa cleaved form of gamma-ENaC at the surface. This increased by 8.5
      fold with Na depletion and decreased by 40% with Na loading. The overall 14-fold
      change reflected regulation of the total abundance of the subunit as well as the
      fraction of the subunit protein in the cleaved form. We conclude that cleavage of
      gamma-ENaC and its expression at the apical surface play a major role in the
      regulation of renal Na reabsorption.

PMID- 19741014
TI  - Regulation of the mitochondrial permeability transition in kidney proximal
      tubules and its alteration during hypoxia-reoxygenation.
AB  - Development of the mitochondrial permeability transition (MPT) can importantly
      contribute to lethal cell injury from both necrosis and apoptosis, but its role
      varies considerably with both the type of cell and type of injury, and it can be
      strongly opposed by the normally abundant endogenous metabolites ADP and Mg(2+).
      To better characterize the MPT in kidney proximal tubule cells and assess its
      contribution to injury to them, we have refined and validated approaches to
      follow the process in whole kidney proximal tubules and studied its regulation in
      normoxic tubules and after hypoxia-reoxygenation (H/R). Physiological levels of
      ADP and Mg(2+) greatly decreased sensitivity to the MPT. Inhibition of
      cyclophilin D by cyclosporine A (CsA) effectively opposed the MPT only in the
      presence of ADP and/or Mg(2+). Nonesterified fatty acids (NEFA) had a large role
      in the decreased resistance to the MPT seen after H/R irrespective of the
      available substrate or the presence of ADP, Mg(2+), or CsA, but removal of NEFA
      was less effective at restoring normal resistance to the MPT in the presence of
      electron transport complex I-dependent substrates than with succinate. The data
      indicate that the NEFA accumulation that occurs during both hypoxia in vitro and
      ischemic acute kidney injury in vivo is a critical sensitizing factor for the MPT
      that overcomes the antagonistic effect of endogenous metabolites and cyclophilin
      D inhibition, particularly in the presence of complex I-dependent substrates,
      which predominate in vivo.

PMID- 19741016
TI  - PKC-dependent superoxide production by the renal medullary thick ascending limb
      from diabetic rats.
AB  - Type 1 diabetes (T1D) is a state of oxidative stress accompanied by PKC
      activation in many tissues. The primary site of O2*- production by the normal rat
      kidney is the medullary thick ascending limb (mTAL). We hypothesized that T1D
      increases O2*- production by the mTAL through a PKC-dependent mechanism involving
      increased expression and translocation of one or more PKC isoforms. mTAL
      suspensions were prepared from rats with streptozotocin-induced T1D (STZ mTALs)
      and from normal or sham rats (normal/sham mTALs). O2*- production by STZ mTALs
      was fivefold higher than normal/sham mTALs (P < 0.05). PMA (30 min) mimicked the
      effect of T1D on O2*- production. Exposure to calphostin C or chelerythrine (PKC
      inhibitors), Go6976 (PKCalpha/beta inhibitor), or rottlerin (PKCdelta inhibitor)
      decreased O2*- production to <20% of untreated baseline in both normal/sham and
      STZ mTALs. PKCbeta inhibitors had no effect. PKC activity was increased in STZ
      mTALs (P < 0.05 vs. normal/sham mTALs) and was unaltered by antioxidant exposure
      (tempol). PKCalpha protein levels were increased by 70% in STZ mTALs, with a
      approximately 30% increase in the fraction associated with the membrane (both P <
      0.05 vs. sham). PKCbeta protein levels were elevated by 29% in STZ mTALs (P <
      0.05 vs. sham) with no change in the membrane-bound fraction. Neither PKCdelta
      protein levels nor its membrane-bound fraction differed between groups. Thus STZ
      mTALs display PKC activation, upregulation of PKCalpha and PKCbeta protein
      levels, increased PKCalpha translocation to the membrane, and accelerated O2*-
      production that is eradicated by inhibition of PKCalpha or PKCdelta (but not
      PKCbeta). We conclude that increased PKCalpha expression and activity are
      primarily responsible for PKC-dependent O2*- production by the mTAL during T1D.

PMID- 19741017
TI  - Enhanced tubuloglomerular feedback in mice with vascular overexpression of A1
      adenosine receptors.
AB  - Adenosine 1 receptors (A1AR) in the kidney are expressed in the vasculature and
      the tubular system. Pharmacological inhibition or global genetic deletion of A1AR
      causes marked reductions or abolishment of tubuloglomerular feedback (TGF)
      responses. To assess the function of vascular A1AR in TGF, we generated
      transgenic mouse lines in which A1AR expression in smooth muscle was augmented by
      placing A1AR under the control of a 5.38-kb fragment of the rat smooth muscle
      alpha-actin promoter and first intron (12). Two founder lines with highest
      expression in the kidney [353 +/- 42 and 575 +/- 43% compared with the wild type
      (WT)] were used in the experiments. Enhanced expression of A1AR at the expected
      site in these lines was confirmed by augmented constrictor responses of isolated
      afferent arterioles to administration of the A1AR agonist N6-cyclohexyladenosine.
      Maximum TGF responses (0-30 nl/min flow step) were increased from 8.4 +/- 0.9
      mmHg in WT (n = 21) to 14.2 +/- 0.7 mmHg in A1AR-transgene (tg) 4 (n = 22; P <
      0.0001), and to 12.6 +/- 1.2 mmHg in A1AR-tg7 (n = 12; P < 0.02). Stepwise
      changes in perfusion flow caused greater numerical TGF responses in A1AR-tg than
      WT in all flow ranges with differences reaching levels of significance in the
      intermediate flow ranges of 7.5-10 and 10-15 nl/min. Proximal-distal single
      nephron glomerular filtration rate (SNGFR) differences (free-flow micropuncture)
      were also increased in A1AR-tg, averaging 6.25 +/- 1.5 nl/min compared with 2.6
      +/- 0.51 nl/min in WT (P = 0.034). Basal plasma renin concentrations as well as
      the suppression of renin secretion after volume expansion were similar in A1AR-tg
      and WT mice, suggesting lack of transgene expression in juxtaglomerular cells.
      These data indicate that A1AR expression in vascular smooth muscle cells is a
      critical component for TGF signaling and that changes in renal vascular A1AR
      expression may determine the magnitude of TGF responses.

PMID- 19741018
TI  - Deletion of Frs2alpha from the ureteric epithelium causes renal hypoplasia.
AB  - Fibroblast growth factor receptor 2 (Fgfr2) signaling is critical in maintaining
      ureteric branching architecture and mesenchymal stromal morphogenesis in the
      kidney. Fibroblast growth factor receptor substrate 2alpha (Frs2alpha) is a major
      docking protein for Fgfr2 with downstream targets including Ets variant (Etv) 4
      and Etv5 in other systems. Furthermore, global deletion of Frs2alpha causes early
      embryonic lethality. The purpose of the study was to determine the role of
      Frs2alpha in mediating Fgfr2 signaling in the ureteric epithelium. To that end,
      we generated mice with conditional deletion of Frs2alpha in the ureteric
      epithelium (Frs2alpha(UB-/-)) and mice with point mutations in the Frs2alpha
      binding site of Fgfr2 (Fgfr2(LR/LR)). Frs2alpha(UB-/-) mice developed mild renal
      hypoplasia characterized by decreased ureteric branching morphogenesis but
      maintained normal overall branching architecture and had normal mesenchymal
      stromal development. Reduced nephron endowment in postnatal mutant mice was
      observed, corresponding with the reduction in branching morphogenesis.
      Furthermore, there were no apparent renal abnormalities in Fgfr2(LR/LR) mice.
      Interestingly, Etv4 and Etv5 expression was unaltered in Frs2alpha(UB-/-) mice,
      as was Sprouty1, an antagonist of Frs2alpha signaling. However, Ret and Wnt11
      (molecules critical for ureteric branching morphogenesis) mRNA levels were lower
      in mutants vs. controls. Taken together, these findings suggest that Fgfr2
      signals through adapter molecules other than Frs2alpha in the ureteric
      epithelium. Furthermore, Frs2alpha may transmit signals through other receptor
      kinases present in ureteric epithelium. Finally, the renal hypoplasia observed in
      Frs2alpha(UB-/-) mice is likely secondary to decreased Ret and Wnt11 expression.

PMID- 19741019
TI  - Proinsulin C-peptide reduces diabetes-induced glomerular hyperfiltration via
      efferent arteriole dilation and inhibition of tubular sodium reabsorption.
AB  - C-peptide reduces diabetes-induced glomerular hyperfiltration in diabetic
      patients and experimental animal models. However, the mechanisms mediating the
      beneficial effect of C-peptide remain unclear. We investigated whether altered
      renal afferent-efferent arteriole tonus or alterations in tubular Na+ transport
      (T(Na)) in response to C-peptide administration mediate the reduction of diabetes
      induced glomerular hyperfiltration. Glomerular filtration rate, filtration
      fraction, total and cortical renal blood flow, total kidney O2 consumption (QO2),
      T(Na), fractional Na+ and Li+ excretions, and tubular free-flow and stop-flow
      pressures were measured in anesthetized adult male normoglycemic and
      streptozotocin-diabetic Sprague-Dawley rats. The specific effect of C-peptide on
      transport-dependent QO2 was investigated in vitro in freshly isolated proximal
      tubular cells. C-peptide reduced glomerular filtration rate (-24%), stop-flow
      pressure (-8%), and filtration fraction (-17%) exclusively in diabetic rats
      without altering renal blood flow. Diabetic rats had higher baseline T(Na)
      (+40%), which was reduced by C-peptide. Similarly, C-peptide increased fractional
      Na+ (+80%) and Li+ (+47%) excretions only in the diabetic rats. None of these
      parameters was affected by vehicle treatments in either group. Baseline QO2 was
      37% higher in proximal tubular cells from diabetic rats than controls and was
      normalized by C-peptide. C-peptide had no effect on ouabain-pretreated diabetic
      cells from diabetic rats. C-peptide reduced diabetes-induced hyperfiltration via
      a net dilation of the efferent arteriole and inhibition of tubular Na+
      reabsorption, both potent regulators of the glomerular net filtration pressure.
      These findings provide new mechanistic insight into the beneficial effects of C
      peptide on diabetic kidney function.

PMID- 19741020
TI  - Mesangial cell-derived factors alter monocyte activation and function through
      inflammatory pathways: possible pathogenic role in diabetic nephropathy.
AB  - Infiltration of macrophages to the kidney is a feature of early diabetic
      nephropathy. For this to happen monocytes must become activated, migrate from the
      circulation, and infiltrate the mesangium. This process involves degradation of
      extracellular matrix, a process mediated by matrix metalloproteinases (MMPs). In
      the present study we investigate the expression of proinflammatory cytokines TNF
      alpha, IL-6, and MMP-9 in glomeruli of control and diabetic rodents and use an in
      vitro coculture system to examine whether factors secreted by mesangial cells in
      response to a diabetic milieu can induce monocyte MMP-9 expression and
      infiltration. After 8 wk of diabetes, the glomerular level of TNF-alpha, IL-6,
      and macrophage number and colocalization of MMP-9 with macrophage were increased
      (P < 0.01). Coculture of THP1 monocytes and glomerular mesangial cells in 5 or 25
      mM glucose increased MMP-9 (5 mM: 65% and 25 mM: 112%; P < 0.05) and conditioned
      media degradative activity (5 mM: 30.0% and 25 mM: 33.5%: P < 0.05). These
      effects were reproduced by addition of mesangial cell conditioned medium to THP1
      cells. High glucose (25 mM) increased TNF-alpha, IL-6, and monocyte
      chemoattractant protein-1 in mesangial cell conditioned medium. These cytokines
      all increased adhesion and differentiation of THP1 cells (P < 0.05), but only TNF
      alpha and IL-6 increased MMP-9 expression (50- and 60-fold, respectively; P <
      0.05). Our results show that mesangial cell-secreted factors increase monocyte
      adhesion, differentiation, MMP expression, and degradative capacity. High glucose
      could augment these effects by increasing mesangial cell proinflammatory cytokine
      secretion. This mesangial cell-monocyte interaction may be important in
      activating monocytes to migrate from the circulation to the kidney in the early
      stages of diabetic nephropathy.

PMID- 19741021
TI  - A review of HIV prevention interventions for juvenile offenders.
AB  - OBJECTIVE: To conduct a critical review of all HIV prevention intervention
      studies conducted with adolescents in juvenile justice settings to inform future
      intervention development. METHOD: PubMed and PsycInfo database searches were
      conducted for peer-reviewed, published HIV prevention intervention studies with
      juvenile offenders. RESULTS: Sixteen studies were identified (N = 3,700
      adolescents). Half of the projects utilized rigorous methodologies to determine
      intervention effect on behavior change, such as conducting a randomized
      controlled trial (n = 8). Nine studies reported behaviors at least 3 months post
      intervention and five out of nine showed decreases in sexual risk behavior.
      CONCLUSIONS: Several HIV prevention programs with juvenile offenders have led to
      sexual risk reduction, although effect sizes are modest. Most existing programs
      have neglected to address the impact of family, mental health, and substance use
      on HIV risk. More work is needed to develop evidence-based interventions that
      include HIV prevention strategies relevant and appropriate for the juvenile
      justice setting.

PMID- 19741022
TI  - Three-way RNA junctions with remote tertiary contacts: a recurrent and highly
      versatile fold.
AB  - Three-way junction RNAs adopt a recurrent Y shape when two of the helices form a
      coaxial stack and the third helix establishes one or more tertiary contacts
      several base pairs away from the junction. In this review, the structure,
      distribution, and functional relevance of these motifs are examined.
      Structurally, the folds exhibit conserved junction topologies, and the distal
      tertiary interactions play a crucial role in determining the final shape of the
      structures. The junctions and remote tertiary contacts behave as flexible hinge
      motifs that respond to changes in the other region, providing these folds with
      switching mechanisms that have been shown to be functionally useful in a variety
      of contexts. In addition, the juxtaposition of RNA domains at the junction and at
      the distal tertiary complexes enables the RNA helices to adopt unusual
      conformations that are frequently used by proteins, RNA molecules, and
      antibiotics as platforms for specific binding. As a consequence of these
      properties, Y-shaped junctions are widely distributed in all kingdoms of life,
      having been observed in small naked RNAs such as riboswitches and ribozymes or
      embedded in complex ribonucleoprotein systems like ribosomal RNAs, RNase P, or
      the signal recognition particle. In all cases, the folds were found to play an
      essential role for the functioning or assembly of the RNA or ribonucleoprotein
      systems that contain them.

PMID- 19741023
TI  - The Borg dyspnoea score: a relevant clinical marker of inspiratory muscle
      weakness in amyotrophic lateral sclerosis.
AB  - The aim of the study was to determine whether the Borg dyspnoea scale could be a
      useful and simple marker to predict respiratory muscle weakness in amyotrophic
      lateral sclerosis (ALS). From April 1997 to 2001, respiratory function was
      perfomed in 72 patients together with the Borg score in both the upright (uBorg)
      and supine (sBorg) positions. Mean upright vital capacity (VC) was 81+/-24%
      predicted, sniff nasal inspiratory pressure (SNIP) was 55+/-26% pred, maximal
      inspiratory pressure (P(I,max)) was 57+/-26% pred and arterial carbon dioxide
      tension (P(a,CO(2))) was 41+/-6 mmHg. The mean Borg scores in the upright and
      supine positions were 1.7+/-1.5 and 2.2+/-2, respectively. A significant
      relationship between SNIP and uBorg (r = 0.4; p = 0.0007) and SNIP and sBorg (r =
      0.58; p<0.0001) was observed. Upright VC, DeltaVC (measured as the supine fall in
      VC as a percentage of seated VC), P(I,max) and P(a,CO(2)) were significantly
      correlated with SNIP. A cut-off value of 3 on the sBorg scale provided the best
      sensitivity (80%) and specificity (78%) (area under the curve 0.8) to predict a
      SNIP < or =40 cmH(2)O, indicating severe inspiratory muscle weakness. Patients
      with a sBorg score > or =3 also exhibited significantly lower VC, P(I,max) and
      twitch mouth pressure during cervical magnetic stimulation, and slightly higher
      P(a,CO(2)) (43.7+/-7 versus 39.2+/-5 mmHg; p = 0.05). The Borg dyspnoea scale is
      a valuable noninvasive test for the prediction of inspiratory muscle weakness in
      ALS patients.

PMID- 19741024
TI  - Determining the aetiology of pulmonary oedema by the oedema fluid-to-plasma
      protein ratio.
AB  - We hypothesised that the oedema fluid-to-plasma protein (EF/PL) ratio, a
      noninvasive measure of alveolar capillary membrane permeability, can accurately
      determine the aetiology of acute pulmonary oedema. 390 mechanically ventilated
      patients with acute pulmonary oedema were enrolled. A clinical diagnosis of acute
      lung injury (ALI), cardiogenic pulmonary oedema or a mixed aetiology was based on
      expert medical record review at the end of hospitalisation. The EF/PL ratio was
      measured from pulmonary oedema fluid and plasma samples collected at intubation.
      209 patients had a clinical diagnosis of ALI, 147 had a diagnosis of cardiogenic
      pulmonary oedema and 34 had a mixed aetiology. The EF/PL ratio had an area under
      the receiver-operating curve of 0.84 for differentiating ALI from cardiogenic
      pulmonary oedema. Using a predefined cut-off of 0.65, the EF/PL ratio had a
      sensitivity of 81% and a specificity of 81% for the diagnosis of ALI. An EF/PL
      ratio >/=0.65 was also associated with significantly higher mortality and fewer
      ventilator-free days. Noninvasive measurement of the EF/PL ratio is a safe and
      reliable bedside method for rapidly determining the aetiology of acute pulmonary
      oedema that can be used at the bedside in both developed and developing
      countries.

PMID- 19741025
TI  - Acute effects of tobacco smoke on human airway dendritic cells in vivo.
AB  - Airway dendritic cells (DCs) play a key role in smoke-related lung diseases;
      however, the acute effects of tobacco smoke on human airway DCs in vivo are
      unknown. A total of 16 smokers underwent bronchoalveolar lavage at two time
      points: directly after a 4-h period of nonsmoking (no smoke exposure); and
      directly after a 4-h period during which eight cigarettes were smoked (acute
      smoke exposure). Using flow cytometry, myeloid DCs (mDCs) and plasmacytoid DCs
      (pDCs), as well as function-associated surface molecules on mDCs, were analysed
      in bronchoalveolar lavage fluid (BALF) and in blood. The numbers of macrophages,
      lymphocytes, neutrophils, eosinophils and pDCs were unchanged in BALF following
      acute smoke exposure, as compared to no smoke exposure. In contrast, there was a
      strong increase in mDC number in BALF and a concomitant decrease in mDC number in
      blood following acute smoke exposure. In addition, acute smoke exposure led to an
      increase in the expression of the surface molecules blood dendritic cell antigen
      1 and 4 and a decrease in the expression of the lung homing receptor, CC
      chemokine receptor 5, on mDCs in BALF. Acute tobacco smoke inhalation results in
      an immediate and selective recruitment of mDCs into human airways, which might
      reflect the very early reaction of the adaptive immune system to smoke exposure.

PMID- 19741026
TI  - Interleukin-17A activation on bronchial epithelium and basophils: a novel
      inflammatory mechanism.
AB  - Basophils are the accessory cell type for T-helper (Th)2 induction and initiators
      in immunoglobulin E-mediated chronic allergic inflammation. Basophils and Th17
      cells accumulate at the inflammatory sites, such as the airways of allergic
      asthmatic patients. We investigated the activation of interleukin (IL)-17A on the
      primary human basophils/KU812 basophilic cells and primary human bronchial
      epithelial cells/BEAS-2B bronchial epithelial cells. Cytokines, chemokines,
      adhesion molecules and intracellular signalling molecules were assayed by ELISA
      or flow cytometry. Co-culture of bronchial epithelial cells and basophils could
      significantly induce the release of IL-6, an epithelial inflammatory cytokine,
      and CCL2, a chemokine for basophils, esosinophils and monocytes. Such induction
      was synergistically enhanced by IL-17A, and direct interaction between these two
      cells was necessary for IL-17A-induced IL-6 and CCL2 release. Surface expression
      of intercellular adhesion molecule-1 on bronchial epithelial cells was also
      upregulated upon their interaction. The interaction of basophils and bronchial
      epithelial cells under IL-17A stimulation was differentially regulated by
      extracellular signal-regulated kinase, c-Jun N-terminal protein kinase, p38
      mitogen-activated protein kinase and nuclear factor-kappaB pathways. These
      findings suggest a novel immunopathological role of Th17 cells and basophils in
      allergic asthma through the activation of granulocyte-mediated inflammation
      initiated by the direct interaction between basophils and bronchial epithelial
      cells.

PMID- 19741027
TI  - Nested PCR in lung tissue for diagnosis of pulmonary tuberculosis.
AB  - Diagnosis of pulmonary tuberculosis (TB) is difficult in cases with an unusual
      presentation and often requires a lung biopsy. The goal of this study was to
      determine the clinical usefulness of nested PCR on lung tissue for the diagnosis
      of pulmonary TB. Clinical and laboratory data were reviewed from patients who
      underwent diagnostic lung biopsies, followed by nested TB PCR on formalin-fixed
      paraffin-embedded lung tissue specimens. The diagnostic yield and clinical impact
      of nested PCR were investigated. Of the 223 patients studied, 142 were diagnosed
      with TB. Microbiologically confirmed TB was identified in 71 patients. Compared
      to culture results, the sensitivity, specificity, positive predictive value and
      negative predictive value of nested PCR were 85%, 99%, 98% and 88%, respectively.
      Nested PCR was more sensitive than acid-fast bacilli smear of respiratory
      specimens and histopathological findings. The PCR results provided an early
      diagnosis and initiation of treatment for TB. However, negative PCR results did
      not lead to discontinuation of unnecessary TB treatment in patients on
      medication. In conclusion, nested PCR on lung tissue specimens is a useful
      diagnostic test for pulmonary TB in patients with an unusual presentation.

PMID- 19741028
TI  - Characterisation of cell adhesion in airway epithelial cell types using electric
      cell-substrate impedance sensing.
AB  - Research on epithelial cell lines and primary epithelium is required to dissect
      the mechanisms underlying the structural abnormalities in airway epithelium
      observed for respiratory diseases, including asthma and chronic obstructive
      pulmonary disease. The novel electric cell-substrate impedance sensing technique
      was used to monitor cell adhesion/spreading, barrier function and wound healing.
      Primary bronchial epithelium was compared with airway epithelial cell lines
      16HBE14o-, BEAS-2B, NCI-H292 and A549. BEAS-2B, A549 and primary cells form a
      confluent monolayer more rapidly than do 16HBE14o- cells. In contrast, 16HBE14o-
      cells form stronger intercellular contacts, with a 10-fold higher resistance than
      BEAS-2B, A549 and NCI-H292 cells and a five-fold increase over primary cells.
      Accordingly, expression of the adhesion molecules zona occludens-1 and E-cadherin
      was highest in 16HBE14o- cells. These molecules were localised in intercellular
      junctions in both 16HBE14o- and primary cells. Finally, restoration of barrier
      function upon injury was impaired in BEAS-2B compared to 16HBE14o- cells. In
      conclusion, epithelial cell types display remarkable phenotypic differences and
      should, accordingly, be used to address specific research questions. 16HBE14o-
      cells appear most suitable for studies on barrier formation, whereas resemblance
      in attachment of primary and BEAS-2B and A549 cells makes the latter more
      important for translational research on cell-matrix contact.

PMID- 19741029
TI  - Prevention of panic attacks and panic disorder in COPD.
AB  - This study examined whether cognitive behavioural therapy (CBT) could prevent the
      development or worsening of panic-spectrum psychopathology and anxiety symptoms
      in chronic obstructive pulmonary disease (COPD). 41 patients with COPD, who had
      undergone pulmonary rehabilitation, were randomised to either a four-session CBT
      intervention condition (n = 21) or a routine care condition (n = 20). Assessments
      were at baseline, post-intervention, and at 6-, 12- and 18-month follow-ups.
      Primary outcomes were the rates of panic attacks, panic disorder and anxiety
      symptoms. Secondary outcomes were depressive symptoms, catastrophic cognitions
      about breathing difficulties, disease-specific quality of life and hospital
      admission rates. There were no significant differences between the groups on
      outcome measures at baseline. By the 18-month follow-up assessment, 12 (60%)
      routine care group participants had experienced at least one panic attack in the
      previous 6 months, with two (17%) of these being diagnosed with panic disorder,
      while no CBT group participants experienced any panic attacks during the follow
      up phase. There were also significant reductions in anxiety symptoms and
      catastrophic cognitions in the CBT group at all three follow-ups and a lower
      number of hospital admissions between the 6- and 12-month follow-ups. The study
      provides evidence that a brief, specifically targeted CBT intervention can treat
      panic attacks in COPD patients and prevent the development and worsening of panic
      spectrum psychopathology and anxiety symptoms.

PMID- 19741030
TI  - Study of prone positioning to reduce ventilator-associated pneumonia in
      hypoxaemic patients.
AB  - The aim of the present study was to examine whether prone positioning (PP)
      affects ventilator associated-pneumonia (VAP) and mortality in patients with
      acute lung injury/adult respiratory distress syndrome. 2,409 prospectively
      included patients were admitted over 9 yrs (2000-2008) to 12 French intensive
      care units (ICUs) (OUTCOMEREA). The patients required invasive mechanical
      ventilation (MV) and had arterial oxygen tension/inspiratory oxygen fraction
      ratios <300 during the first 48 h. Controls were matched to PP patients on the PP
      propensity score (+/-10%), MV duration longer than that in PP patients before the
      first turn prone, and centre. VAP incidence was similar in the PP and control
      groups (24 versus 13 episodes.1,000 patient-days MV(-1) respectively, p = 0.14).
      After adjustment, PP did not decrease VAP occurrence (HR 1.64 (95% CI 0.70-3.84);
      p = 0.25) but significantly delayed hospital mortality (HR 0.56 (95% CI 0.39
      0.79); p = 0.001), without decreasing 28-day mortality (37% in both groups). Post
      hoc analyses indicated that PP did not protect against VAP but, when used for >1
      day, might decrease mortality and benefit the sickest patients (Simplified Acute
      Physiology Score >50). In ICU patients with hypoxaemic acute respiratory failure,
      PP had no effect on the risk of VAP. PP delayed mortality without decreasing 28
      day mortality. PP >1 day might decrease mortality, particularly in the sickest
      patients.

PMID- 19741032
TI  - National income, self-reported wheezing and asthma diagnosis from the World
      Health Survey.
AB  - The aims of this study were to quantify and describe the variations in
      respiratory symptoms and diagnosis prevalence across regions of the world
      according to national income. In 2002 and 2003, the World Health Organization
      implemented the World Health Survey (WHS), which used a standardised survey
      instrument to compile comprehensive baseline information on health and healthcare
      expenditure. We analysed the WHS data to assess the global patterns of self
      reported wheeze and doctor-diagnosed asthma, two commonly reported measures of
      respiratory health. In total there were 308,218 participants with complete
      records, from 64 countries. The weighted mean age of the survey population was 43
      yrs. Global prevalence of current wheezing symptoms ranged from 2.4% in Vietnam
      to 24% in Brazil; the prevalence of diagnosed asthma ranged from 1.8% in Vietnam
      to 32.8% in Australia. Overall, the prevalence of symptoms and diagnosis showed a
      U-shaped pattern with the largest prevalence reported in low- and high-income
      countries. The smallest prevalence was consistently found in middle-income
      countries. These WHS analyses have provided global prevalence estimates of wheeze
      and doctor-diagnosed asthma using data gathered simultaneously and consistently
      across six continents. These findings support the need for continued global
      respiratory illness surveillance for disease prevention, health policy and
      management.

PMID- 19741033
TI  - New concepts for expressing forced expiratory volume in 1 s arising from survival
      analysis.
AB  - Spirometric lung function is partly determined by sex, age and height (Ht).
      Commonly, lung function is expressed as a percentage of the predicted value (PP)
      in order to account for these effects. Since the PP method retains sex, age and
      Ht bias, forced expiratory volume in 1 s (FEV(1)) standardised by powers of Ht
      and by a new sex-specific lower limit (FEV(1) quotient (FEV(1)Q)) were
      investigated to determine which method best predicted all-cause mortality in
      >26,967 patients and normal subjects. On multivariate analysis, FEV(1)Q was the
      best predictor, with a hazard ratio for the worst decile of 6.9 compared to 4.1
      for FEV(1)PP. On univariate analysis, the hazard ratios were 18.8 compared to
      6.1, respectively; FEV(1) x Ht(-3) was the next-best predictor of survival.
      Median survival was calculated for simple cut-off values of FEV(1)Q and FEV(1) x
      Ht(-3). These survival curves were accurately fitted (r(2) = 1.0) by both FEV(1)Q
      and FEV(1) x Ht(-3) values expressed polynomially, and so an individual's test
      result could be used to estimate survival (with sd for median survival of 0.22
      and 0.61 yrs, respectively). It is concluded that lung function impairment should
      be expressed in a new way, here termed the FEV(1)Q, or, alternatively, as FEV(1)
      x Ht(-3), since these indices best relate spirometric lung function to all-cause
      mortality and survival.

PMID- 19741034
TI  - Stress failure plays a major role in the development of high-altitude pulmonary
      oedema in rats.
AB  - Hypoxia and exertion are considered as the two main factors in the development of
      high-altitude pulmonary oedema (HAPE), however its pathophysiology remains
      unclear. Therefore, we established a model in which 32 Sprague-Dawley rats were
      randomly assigned to normoxic rest, hypoxic rest, normoxic exercise and hypoxic
      exercise. An altitude of 4,700 m was simulated using hypobaric hypoxia, while
      exercise consisted 48 h walk with 15-20 min breaks every 4 h. Arterial blood gas,
      bronchoalveolar lavage (BAL), lung wet-to-dry weight (W/D) ratio and histological
      measurements were conducted on each animal. In rats exercising in hypoxia, BAL
      protein and lung W/D ratio were significantly increased but no changes in BAL
      leukotriene B(4) and immunoglobulin M were observed. In the same group, lung
      histology showed typical haemorrhagic lung oedema and disruption of both alveolar
      epithelium and capillary endothelium while hypoxia or exertion alone only induced
      slight endothelium and epithelium swelling/disruption. Our study established a
      direct link between histological and physiological evidence of HAPE-like symptoms
      and we demonstrated that hypoxia and exertion can synergistically induce HAPE
      like symptoms in Sprague-Dawley rats without inducing lung inflammation. We
      therefore propose that alveolar epithelium and capillary endothelium stress
      failure play a major role in the development of HAPE.

PMID- 19741035
TI  - Purification and mechanism of human aldehyde oxidase expressed in Escherichia
      coli.
AB  - Human aldehyde oxidase 1 (AOX1) has been subcloned into a vector suitable for
      expression in Escherichia coli, and the protein has been expressed. The resulting
      protein is active, with sulfur being incorporated in the molybdopterin cofactor.
      Expression levels are modest, but 1 liter of cells supplies enough protein for
      both biochemical and kinetic characterization. Partial purification is achieved
      by nickel affinity chromatography through the addition of six histidines to the
      amino-terminal end of the protein. Kinetic analysis, including kinetic isotope
      effects and comparison with xanthine oxidase, reveal similar mechanisms, with
      some subtle differences. This expression system will allow for the interrogation
      of human aldehyde oxidase structure/function relationships by site-directed
      mutagenesis and provide protein for characterizing the role of AOX1 in drug
      metabolism.

PMID- 19741036
TI  - Comparison of blood-brain barrier transport of glial-derived neurotrophic factor
      (GDNF) and an IgG-GDNF fusion protein in the rhesus monkey.
AB  - The brain drug development of glial-derived neurotrophic factor (GDNF) is
      prevented by the lack of transport of this protein across the blood-brain barrier
      (BBB). GDNF transport across the BBB can be made possible by re-engineering the
      neurotrophin as a fusion protein with a genetically engineered monoclonal
      antibody (MAb) against the human insulin receptor (HIR), which crosses the BBB on
      the endogenous insulin receptor. The present work was designed to compare the BBB
      transport in vivo of GDNF and the HIR MAb-GDNF fusion protein. Owing to species
      specificity of HIR MAb binding to the insulin receptor, the present studies were
      performed in the adult rhesus monkey. The brain uptake of human IgG1 was
      determined to assess the uptake of a brain plasma volume marker. The brain
      clearance of GDNF was no different from the clearance of the IgG1, which
      indicated GDNF does not cross the primate BBB in vivo. In contrast, BBB transport
      of the HIR MAb-GDNF fusion protein was shown with film and emulsion
      autoradiography, as well as the capillary depletion method. In parallel with the
      increased brain uptake, fusion of the GDNF to the HIR MAb resulted in a decrease
      in the uptake of GDNF by liver, spleen, and kidney. Administration of the HIR MAb
      GDNF fusion protein had no effect on glycemic control. The brain uptake
      parameters show that a systemic dose of the HIR MAb-GDNF fusion protein of 0.2
      mg/kg may generate a 10-fold increase in the cerebral concentration of GDNF in
      the human brain.

PMID- 19741037
TI  - Endogenous gene and protein expression of drug-transporting proteins in cell
      lines routinely used in drug discovery programs.
AB  - The aim of this study was to investigate the gene and protein expression profiles
      of important drug-transporting proteins in human cell lines commonly used for
      studies of drug transport mechanisms. Human cell lines used to transiently or
      stably express single transporters [HeLa, human embryonic kidney (HEK) 293] and
      leukemia cell lines used to study drug resistance by ATP-binding cassette
      transporters (HL-60, K562) were investigated and compared with organotypic cell
      lines (HepG2, Saos-2, Caco-2, and Caco-2 TC7). For gene expression studies, real
      time polymerase chain reaction was used, whereas monospecific polyclonal
      antibodies were generated and used to investigate protein expression by
      immunohistochemistry. Thirty-six transporters were studied for gene expression,
      and nine were studied for protein expression. The antibodies were validated using
      expression patterns in human tissues. Finally, the function of one ubiquitously
      expressed transporter, MCT1/SLC16A1, was investigated using [(14)C]lactic acid as
      a substrate. In general, the adherent cell lines (HeLa, HEK293) displayed low
      transporter expression, and the expression patterns were barely affected by
      transfection. The leukemia cell lines (K562, HL-60) and Saos-2 also had low
      endogenous transporter expression, whereas the organotypic cell lines (HepG2 and
      Caco-2) showed higher expression of some transporters. Comparison of gene and
      protein expression profiles gave poor correlations, but better agreement was
      obtained for antibodies with a good validation score, indicating that antibody
      quality was a significant variable. It is noteworthy that the monocarboxylic acid
      transporting protein MCT1 was significantly expressed in all and was functional
      in most of the cell lines, indicating that MCT1 may be a confounding factor when
      the transport of small anionic drugs is investigated.

PMID- 19741039
TI  - The uPA(+/+)-SCID mouse with humanized liver as a model for in vivo metabolism of
      4-androstene-3,17-dione.
AB  - The metabolism in primary human hepatocyte cultures often deviates from that in
      clinical studies, which in turn are hampered by ethical constraints. Here the use
      of urokinase-type plasminogen activator-severe combined immunodeficiency
      [uPA(+/+)-SCID] mice transplanted with human hepatocytes was investigated as a
      model for in vivo metabolic studies. The urinary excretion profile after oral
      administration of 4-androstene-3,17-dione (AD) in chimeric mice was investigated
      by using gas chromatography-mass spectrometry detection and was compared with
      previously reported metabolites of AD in humans and cell cultures. Chimeric mice
      exhibited an AD metabolic profile similar to that of humans, showing androsterone
      and etiocholanolone as major metabolites. Several hydroxylated steroids were
      detected as minor metabolites in the chimeric mice compared with hepatocyte
      cultures. A significant correlation between the extent of liver replacement and
      the relative abundances of human-type metabolites was established. The results
      for AD showed that humanized liver uPA-SCID mice can serve as an alternative
      model for in vivo metabolism studies in humans. In the future, this model could
      possibly be used for other steroids or pharmaceutical compounds.

PMID- 19741038
TI  - Interaction of macrolide antibiotics with intestinally expressed human and rat
      organic anion-transporting polypeptides.
AB  - The macrolide antibiotics azithromycin and clarithromycin are large molecular
      weight compounds that exhibit moderate to excellent oral bioavailability in
      preclinical species and humans. Previous concomitant dosing studies in rats using
      rifamycin SV, a general organic anion-transporting polypeptide (OATP) inhibitor,
      suggested that the high oral absorption of azithromycin and clarithromycin may be
      caused by facilitative uptake by intestinal Oatps. In this study, we used
      OATP/Oatp-expressing cells to investigate the interaction of macrolides with rat
      Oatp1a5, human OATP1A2, and human/rat OATP2B1/Oatp2b1. These experiments showed
      that azithromycin and clarithromycin were potent inhibitors of rat Oatp1a5
      mediated taurocholate uptake with apparent inhibitor constant (K(i)) values of
      3.3 and 2.4 microM, respectively. The macrolides functioned as noncompetitive
      inhibitors but were not transport substrates for rat Oatp1a5, as assessed by
      direct uptake measurements of radiolabeled azithromycin and clarithromycin. cis
      Inhibition and direct uptake studies further showed that azithromycin and
      clarithromycin were only very weak inhibitors and not substrates for human
      OATP1A2 and human/rat OATP2B1/Oatp2b1. In summary, these results indicate that
      the macrolides azithromycin and clarithromycin potently inhibit rat Oatp1a5 but
      do not significantly interact with OATP1A2 and OATP2B1/Oatp2b1. These
      intestinally expressed OATP/Oatp(s) are not responsible for the postulated
      facilitative uptake of azithromycin and clarithromycin, and alternative
      facilitative pathways must exist for their intestinal absorption.

PMID- 19741040
TI  - Effects of short-term and long-term pretreatment of Schisandra lignans on
      regulating hepatic and intestinal CYP3A in rats.
AB  - This study aimed to evaluate the effects of Schisandra lignan extract (SLE) with
      short- and long-term pretreatment on regulating rat hepatic and intestinal CYP3A
      for a comprehensive evaluation of metabolism-based herb-drug interactions.
      Inhibitory effects of SLE and its major components on rat CYP3A were confirmed in
      both hepatic and intestinal microsomal incubation systems. After a single dose of
      SLE pretreatment, higher C(max) and area under the concentration-time curves from
      zero to infinity (AUC(0-infinity)) values were observed for intragastric
      midazolam (MDZ), whereas those for the intravenous MDZ were little changed. The
      mechanism-based inhibition of SLE toward CYP3A was further confirmed in vivo,
      characterized with a recovery half-life of 38 h. In contrast, SLE long-term
      treatment enhanced both hepatic (2.5-fold) and intestinal (4.0-fold) CYP3A
      protein expression and promoted the in vivo clearance of MDZ. When MDZ was
      coadministered with SLE after a consecutive long-term treatment, the AUC(0
      infinity) value of MDZ was still lower than that of the control group, suggesting
      a much stronger inducing than inhibiting effect of SLE toward CYP3A. Furthermore,
      the intragastric administration of SLE exhibited a more intensive regulating
      effect toward intestinal than hepatic CYP3A, which could be partially explained
      by the relatively high exposures of lignans in the intestine. In conclusion, this
      study provides a comprehensive map for showing the complicated effects of SLE and
      its components on regulating rat CYP3A. The important findings are that SLE
      possesses a much stronger inducing than inhibiting effect on CYP3A, as well as a
      more intensive regulating effect on intestinal than hepatic CYP3A.

PMID- 19741041
TI  - Air pollution and hospitalization for headache in Chile.
AB  - The authors performed a time-series analysis to test the association between air
      pollution and daily numbers of hospitalizations for headache in 7 Chilean urban
      centers during the period 2001-2005. Results were adjusted for day of the week
      and humidex. Three categories of headache-migraine, headache with cause
      specified, and headache not otherwise specified-were all associated with air
      pollution. Relative risks for migraine associated with interquartile-range
      increases in specific air pollutants were as follows: 1.11 (95% confidence
      interval (CI): 1.06, 1.17) for a 1.15-ppm increase in carbon monoxide; 1.11 (95%
      CI: 1.06, 1.17) for a 28.97-microg/m(3) increase in nitrogen dioxide; 1.10 (95%
      CI: 1.04, 1.17) for a 6.20-ppb increase in sulfur dioxide; 1.17 (95% CI: 1.08,
      1.26) for a 69.51-ppb increase in ozone; 1.11 (95% CI: 1.00, 1.19) for a 21.51
      microg/m(3) increase in particulate matter less than 2.5 mum in aerodynamic
      diameter (PM(2.5)); and 1.10 (95% CI: 1.04, 1.15) for a 37.79-microg/m(3)
      increase in particulate matter less than 10 mum in aerodynamic diameter (PM(10)).
      There was no significant effect modification by age, sex, or season. The authors
      conclude that air pollution appears to increase the risk of headache in Santiago
      Province. If the relation is causal, the morbidity associated with headache
      should be considered when estimating the burden of illness and costs associated
      with poor air quality.

PMID- 19741042
TI  - Biomarker validation of reports of recent sexual activity: results of a
      randomized controlled study in Zimbabwe.
AB  - Challenges in the accurate measurement of sexual behavior in human
      immunodeficiency virus (HIV) prevention research are well documented and have
      prompted discussion about whether valid assessments are possible. Audio computer
      assisted self-interviewing (ACASI) may increase the validity of self-reported
      behavioral data. In 2006-2007, Zimbabwean women participated in a randomized,
      cross-sectional study that compared self-reports of recent vaginal sex and condom
      use collected through ACASI or face-to-face interviewing (FTFI) with a validated
      objective biomarker of recent semen exposure (prostate-specific antigen (PSA)
      levels). Of 910 study participants, 196 (21.5%) tested positive for PSA, an
      indication of semen exposure during the previous 2 days. Of these 196
      participants, 23 (11.7%) reported no sex in the previous 2 days, with no
      difference in reported sexual activity between interview modes (12.5% ACASI vs.
      10.9% FTFI; Fisher's exact test: P = 0.72). In addition, 71 PSA-positive
      participants (36.2%) reported condom-protected vaginal sex only; their reports
      also indicated no difference between interview modes (33.7% ACASI vs. 39.1% FTFI;
      P = 0.26). Only 52% of PSA-positive participants reported unprotected sex during
      the previous 2 days. Self-report was a poor predictor of recent sexual activity
      and condom use in this study, regardless of interview mode, providing evidence
      that such data should be interpreted cautiously.

PMID- 19741043
TI  - Maternal catecholamine levels in midpregnancy and risk of preterm delivery.
AB  - Associations between stress hormones and preterm delivery have not been fully
      explored. In this study, pregnant women enrolled from 52 clinics in 5 Michigan
      communities (1998-2004) provided urine samples for 3 days (waking and bedtime)
      during midpregnancy. Urinary catecholamine levels (epinephrine, norepinephrine,
      and dopamine) were measured in a subcohort (247 preterm and 760 term deliveries),
      and a 3-day median value was calculated. Polytomous logistic regression models
      assessed relations between catecholamine quartiles (of the median) and a 4-level
      outcome variable (i.e., term (referent) and 3 preterm delivery subtypes:
      spontaneous; premature rupture of membranes; and medically indicated). Final
      models incorporated other relevant covariates (e.g., creatinine, demographic,
      behavior). The risk of spontaneous preterm delivery was increased in the highest
      versus lowest quartile of norepinephrine and dopamine: norepinephrine, waking
      (adjusted odds ratio (AOR) = 3.7, 95% confidence interval (CI): 1.8, 7.9) and
      bedtime (AOR = 2.5, 95% CI: 1.3, 4.9); dopamine, waking (AOR = 2.6, 95% CI: 1.4,
      5.1) and bedtime (AOR = 2.3, 95% CI: 1.2, 4.6). Adjusted odds ratios were further
      strengthened after removing women whose placentas showed evidence of acute
      infection or vascular pathology. High catecholamine levels in maternal urine may
      be indicative of excess stressors and/or predisposition to elevated sympathetic
      activation that contributes to increased risk of spontaneous preterm delivery.

PMID- 19741044
TI  - Test-retest reliability of a sexual behavior interview for men residing in
      Brazil, Mexico, and the United States: the HPV in Men (HIM) Study.
AB  - Understanding the natural history of sexually transmitted infections requires the
      collection of data on sexual behavior. However, there is concern that self
      reported information on sexual behavior may not be valid, especially if study
      participants are culturally and linguistically distinct. The authors completed a
      test-retest reliability study of 1,069 men recruited in Brazil, Mexico, and the
      United States in 2005 and 2006. All of the men completed the same computer
      assisted self-interview approximately 3 weeks apart. Refusal rates, kappa
      coefficients, and intraclass correlation coefficients were calculated for the
      full sample and by country, age, and lifetime number of female sex partners.
      Reliability coefficients for each study site and the combined population were
      high for almost all questions. With few exceptions, the authors found high test
      retest reliability with a computer-assisted self-interview on sexual behavior
      used in 3 culturally and linguistically distinct countries.

PMID- 19741045
TI  - Thyroid hormone receptors regulate adipogenesis and carcinogenesis via crosstalk
      signaling with peroxisome proliferator-activated receptors.
AB  - Peroxisome proliferator-activated receptors (PPARs) and thyroid hormone receptors
      (TRs) are members of the nuclear receptor superfamily. They are ligand-dependent
      transcription factors that interact with their cognate hormone response elements
      in the promoters to regulate respective target gene expression to modulate
      cellular functions. While the transcription activity of each is regulated by
      their respective ligands, recent studies indicate that via multiple mechanisms
      PPARs and TRs crosstalk to affect diverse biological functions. Here, we review
      recent advances in the understanding of the molecular mechanisms and biological
      impact of crosstalk between these two important nuclear receptors, focusing on
      their roles in adipogenesis and carcinogenesis.

PMID- 19741046
TI  - Hormone- and light-mediated regulation of heat-induced differential petiole
      growth in Arabidopsis.
AB  - Plants react quickly and profoundly to changes in their environment. A sudden
      increase in temperature, for example, induces differential petiole growth-driven
      upward leaf movement (hyponastic growth) in Arabidopsis (Arabidopsis thaliana).
      We show that accessions that face the strongest fluctuations in diurnal
      temperature in their natural habitat are least sensitive for heat-induced
      hyponastic growth. This indicates that heat-induced hyponastic growth is a trait
      subject to natural selection. The response is induced with kinetics remarkably
      similar to ethylene- and low light-induced hyponasty in several accessions. Using
      pharmacological assays, transcript analysis, and mutant analyses, we demonstrate
      that ethylene and the photoreceptor protein phytochrome B are negative regulators
      of heat-induced hyponastic growth and that low light, phytochrome A, auxin, polar
      auxin transport, and abscisic acid are positive regulators of heat-induced
      hyponastic growth. Furthermore, auxin, auxin polar transport, phytochrome A,
      phytochrome B, and cryptochromes are required for a fast induction of heat
      induced hyponastic growth.

PMID- 19741047
TI  - Mutagenesis and beyond! Tools for understanding legume biology.

PMID- 19741048
TI  - Vascular function in grape berries across development and its relevance to
      apparent hydraulic isolation.
AB  - During the latter stages of development in fleshy fruit, water flow through the
      xylem declines markedly and the requirements of transpiration and further
      expansion are fulfilled primarily by the phloem. We evaluated the hypothesis that
      cessation of water transport through the xylem results from disruption or
      occlusion of pedicel and berry xylem conduits (hydraulic isolation). Xylem
      hydraulic resistance (R(h)) was measured in developing fruit of grape (Vitis
      vinifera 'Chardonnay') 20 to 100 d after anthesis (DAA) and compared with
      observations of xylem anatomy by light and cryo-scanning electron microscopy and
      expression of six plasma membrane intrinsic protein (PIP) aquaporin genes
      (VvPIP1;1, VvPIP1;2, VvPIP1;3, VvPIP2;1, VvPIP2;2, VvPIP2;3). There was a
      significant increase in whole berry R(h) and receptacle R(h) in the latter stages
      of ripening (80-100 DAA), which was associated with deposition of gels or solutes
      in many receptacle xylem conduits. Peaks in the expression of some aquaporin
      isoforms corresponded to lower whole berry R(h) 60 to 80 DAA, and the increase in
      R(h) beginning at 80 DAA correlated with decreases in the expression of the two
      most predominantly expressed PIP genes. Although significant, the increase in
      berry R(h) was not great enough, and occurred too late in development, to explain
      the decline in xylem flow that occurs at 60 to 75 DAA. The evidence suggests that
      the fruit is not hydraulically isolated from the parent plant by xylem occlusion
      but, rather, is "hydraulically buffered" by water delivered via the phloem.

PMID- 19741049
TI  - The grapevine R2R3-MYB transcription factor VvMYBF1 regulates flavonol synthesis
      in developing grape berries.
AB  - Flavonols are important ultraviolet light protectants in many plants and
      contribute substantially to the quality and health-promoting effects of fruits
      and derived plant products. To study the regulation of flavonol synthesis in
      fruit, we isolated and characterized the grapevine (Vitis vinifera 'Shiraz') R2R3
      MYB transcription factor VvMYBF1. Transient reporter assays established VvMYBF1
      to be a specific activator of flavonol synthase1 (VvFLS1) and several other
      promoters of grapevine and Arabidopsis (Arabidopsis thaliana) genes involved in
      flavonol synthesis. Expression of VvMYBF1 in the Arabidopsis mutant myb12
      resulted in complementation of its flavonol-deficient phenotype and confirmed the
      function of VvMYBF1 as a transcriptional regulator of flavonol synthesis.
      Transcript analysis of VvMYBF1 throughout grape berry development revealed its
      expression during flowering and in skins of ripening berries, which correlates
      with the accumulation of flavonols and expression of VvFLS1. In addition to its
      developmental regulation, VvMYBF1 expression was light inducible, implicating
      VvMYBF1 in the control of VvFLS1 transcription. Sequence analysis of VvMYBF1 and
      VvFLS1 indicated conserved putative light regulatory units in promoters of both
      genes from different cultivars. By analysis of the VvMYBF1 amino acid sequence,
      we identified the previously described SG7 domain and an additional sequence
      motif conserved in several plant MYB factors. The described motifs have been used
      to identify MYB transcription factors from other plant species putatively
      involved in the regulation of flavonol biosynthesis. To our knowledge, this is
      the first functional characterization of a light-inducible MYB transcription
      factor controlling flavonol synthesis in fruit.

PMID- 19741050
TI  - A leaky mutation in DWARF4 reveals an antagonistic role of brassinosteroid in the
      inhibition of root growth by jasmonate in Arabidopsis.
AB  - The F-box protein CORONATINE INSENSITIVE1 (COI1) plays a central role in
      jasmonate (JA) signaling and is required for all JA responses in Arabidopsis
      (Arabidopsis thaliana). To dissect JA signal transduction, we isolated the
      partially suppressing coi1 (psc1) mutant, which partially suppressed coi1
      insensitivity to JA inhibition of root growth. The psc1 mutant partially restored
      JA sensitivity in coi1-2 background and displayed JA hypersensitivity in wild
      type COI1 background. Genetic mapping, sequence analysis, and complementation
      tests revealed that psc1 is a leaky mutation of DWARF4 (DWF4) that encodes a key
      enzyme in brassinosteroid (BR) biosynthesis. Physiological analysis showed that
      an application of exogenous BR eliminated the partial restoration of JA
      sensitivity by psc1 in coi1-2 background and the JA hypersensitivity of psc1 in
      wild-type COI1 background. Exogenous BR also attenuated JA inhibition of root
      growth in the wild type. In addition, the expression of DWF4 was inhibited by JA,
      and this inhibition was dependent on COI1. These results indicate that (1) BR is
      involved in JA signaling and negatively regulates JA inhibition of root growth,
      and (2) the DWF4 is down-regulated by JA and is located downstream of COI1 in the
      JA-signaling pathway.

PMID- 19741051
TI  - A type I interferon signature in monocytes is associated with poor response to
      interferon-beta in multiple sclerosis.
AB  - The effect of interferon-beta in multiple sclerosis is modest and many patients
      do not respond to treatment. To date, no single biomarker reliably correlates
      with responsiveness to interferon-beta in multiple sclerosis. In the present
      study, genome-wide expression profiling was performed in peripheral blood
      mononuclear cells from 47 multiple sclerosis patients treated with interferon
      beta for a minimum of 2 years and classified as responders and non-responders
      based on clinical criteria. A validation cohort of 30 multiple sclerosis patients
      was included in the study to replicate gene-expression findings. Before
      treatment, interferon-beta responders and non-responders were characterized by
      differential expression of type I interferon-induced genes with overexpression of
      the type interferon-induced genes in non-responders. Upon treatment the
      expression of these genes remained unaltered in non-responders, but was strongly
      upregulated in responders. Functional experiments showed a selective increase in
      phosphorylated STAT1 levels and interferon receptor 1 expression in monocytes of
      non-responders at baseline. When dissecting this type I interferon signature
      further, interferon-beta non-responders were characterized by increased monocyte
      type I interferon secretion upon innate immune stimuli via toll-like receptor 4,
      by increased endogenous production of type I interferon, and by an elevated
      activation status of myeloid dendritic cells. These findings indicate that
      perturbations of the type I interferon signalling pathway in monocytes are
      related to lack of response to interferon-beta, and type I interferon-regulated
      genes may be used as response markers in interferon-beta treatment.

PMID- 19741052
TI  - Learning from international policies on trans fatty acids to reduce
      cardiovascular disease in low- and middle-income countries, using Mexico as a
      case study.
AB  - Trans fatty acids (TFA) are a major risk factor for cardiovascular disease (CVD),
      and are consumed in large quantities in low- and middle-income countries as they
      are used to produce low cost, commonly eaten processed food products.
      International organizations agree that evidence linking TFA and CVD is strong
      enough to warrant public health action. This study investigates barriers and
      opportunities that exist for TFA policy development in low- and middle-income
      countries, through a literature review of international TFA policy and
      stakeholder analysis. Previous national policy responses have mostly been in
      developed countries. Voluntary reduction of TFA by the food industry, following
      food labelling and/or consumer lobbying, has been the approach in several
      countries but with varying levels of success, and resulting in major differences
      in formulation of products between countries. Canada and New York have now moved
      from voluntary to mandatory approaches. Only three countries have regulated the
      TFA content of food. Common factors for successful TFA reduction include
      increased consumer and political awareness of the health impacts of TFA and the
      need for champion consumer organizations. A stakeholder analysis, using the
      Mexican policy context as a case study, explored contextual issues influencing
      implementation of TFA regulation in low- or middle-income countries. Although the
      public health context seemed to be appropriate to promote TFA policy, the issue
      is not on the political agenda because it lacks legitimacy and support as a
      health or regulatory issue. The food industry and government resist the need for
      regulation, and there is no organized health or consumer lobby to counter this.
      This is likely to be the case in other middle- and low-income countries.

PMID- 19741053
TI  - Functional significance of muscarinic receptor expression within the proximal and
      distal rat vagina.
AB  - Information regarding the role of cholinergic nerves in mediating vaginal smooth
      muscle contraction is sparse, and in vitro studies of the effects of muscarinic
      agonists on vaginal smooth muscle are discrepant. The goal of this study was to
      determine the expression of muscarinic receptors in the vaginal wall of the rat.
      In addition, we sought to determine the effect of the muscarinic receptor agonist
      carbachol on contractility and inositol phosphate production of the proximal and
      distal rat vaginal muscularis. RT-PCR analysis indicated that both M(2) and M(3)
      receptor transcripts were expressed within the proximal and distal rat vagina.
      Carbachol dose-dependently (10(-7)-10(-4) M) contracted the rat vaginal
      muscularis with a greater maximal contractile response in the proximal vagina (P
      < 0.01) compared with the distal vagina. The contractile responses of the rat
      vaginal muscularis to carbachol were dose dependently inhibited by the M(3)
      antagonist para-fluoro-hexahydrosiladefenidol, and a pK(B) of 7.78 and 7.95 was
      calculated for the proximal and distal vagina, respectively. Inositol phosphate
      production was significantly increased in both regions of the vagina following 20
      min exposure to 50 muM carbachol with higher levels detected in the proximal
      vagina compared with the distal (P < 0.05). Preliminary experiments indicated the
      presence of M(2) and M(3) receptors in the human vaginal muscularis as well as
      contraction of human vaginal muscularis to carbachol, indicating that our animal
      studies are relevant to human tissue. Our results provide strong evidence for the
      functional significance of M(3) receptor expression in the vaginal muscularis.

PMID- 19741054
TI  - Eicosapentaenoic acid attenuates arthritis-induced muscle wasting acting on
      atrogin-1 and on myogenic regulatory factors.
AB  - Eicosapentaenoic acid (EPA) is an omega-3 polyunsaturated fatty acid that has
      anti-inflammatory and anticachectic actions. The aim of this work was to
      elucidate whether EPA administration is able to prevent an arthritis-induced
      decrease in body weight and muscle wasting in rats. Arthritis was induced by
      intradermal injection of Freund's adjuvant; 3 days later, nine rats received 1
      g/kg EPA or coconut oil daily. All rats were killed 15 days after adjuvant
      injection. EPA administration decreased the external signs of arthritis and paw
      volume as well as liver TNF-alpha mRNA. EPA did not modify arthritis-induced
      decrease in food intake or body weight gain. However, EPA treatment prevented
      arthritis-induced increase in muscle TNF-alpha and atrogin-1, whereas it
      attenuated the decrease in gastrocnemius weight and the increase in MuRF1 mRNA.
      Arthritis not only decreased myogenic regulatory factors but also increased PCNA,
      MyoD, and myogenin mRNA in the gastrocnemius. Western blot analysis showed that
      changes in protein content followed the pattern seen with mRNA. In the control
      rats, EPA administration increased PCNA and MyoD mRNA and protein. In arthritic
      rats, EPA did not modify the stimulatory effect of arthritis on these myogenic
      regulatory factors. The results suggest that in experimental arthritis, in
      addition to its anti-inflammatory effect, EPA treatment attenuates muscle wasting
      by decreasing atrogin-1 and MuRF1 gene expression and increasing the
      transcription factors that regulate myogenesis.

PMID- 19741055
TI  - Maternal hemoglobin level and fetal outcome at low and high altitudes.
AB  - Both, low (<7 g/dl) and high (>14.5 g/dl), maternal hemoglobin (Hb) levels have
      been related to poor fetal outcome. Most studies have been done at low altitude
      (LA). Here, we have sought to determine whether this relationship exists at both
      high and low altitude, and also whether there is an adverse effect of high
      altitude (HA) on fetal outcome independent of level of maternal hemoglobin. The
      study is based on a retrospective multicenter analysis of 35,449 pregnancies at
      LA and six other cities above 3000 meters. In analyses of all women at both LA
      and HA, those with Hb <9 g/dl had odds ratios (ORs) and 95% confidence intervals
      (CI) of 4.4 (CI: 2.8-6.7), 2.5 (CI: 1.9-3.2), and 1.4 (CI: 1.1-1.9) for
      stillbirths, preterm, and small for gestational age (SGA) births, respectively,
      compared with women with 11-12.9 g/dl of Hb, after adjustment for confounders.
      These risks by hemoglobin level differed little between women at LA and HA,
      suggesting that no correction of the definition of anemia is necessary for women
      at HA. Women living at high altitude with hemoglobin >15.5 g/dl had higher risks
      for stillbirths (OR: 1.3; CI: 1.05-1.3), preterm (OR: 1.5; CI 1.3-1.8), and SGA
      births (OR: 2.1, CI 1.8-2.3). There was also a significant adverse effect of
      living at HA, independent of hemoglobin level for all three outcomes (OR: 3.9,
      1.7, and 2.3; CI: 2.8-5.2, 1.5-1.9, and 2.1-2.5) for stillbirths, preterms, and
      SGA respectively, after adjusting for hemoglobin level. Both, high and low
      maternal hemoglobin levels were related to poor pregnancy outcome, with similar
      effect of low hemoglobin in both LA and HA. Our data suggest, that maternal
      hemoglobin above 11 g/dl but below 13 g/dl is the area of minimal risk of poor
      adverse outcomes. Living at HA had an adverse effect independent of hemoglobin
      level.

PMID- 19741056
TI  - Calcium-dependent phosphodiesterase 1C inhibits renin release from isolated
      juxtaglomerular cells.
AB  - Renin release from the juxtaglomerular (JG) cell is stimulated by the second
      messenger cAMP and inhibited by calcium. We previously showed JG cells contain a
      calcium sensing receptor (CaSR), which, when stimulated, decreases cAMP formation
      and inhibits renin release. We hypothesize CaSR activation decreases cAMP and
      renin release, in part, by stimulating a calcium calmodulin-activated
      phosphodiesterase 1 (PDE1). We incubated our primary culture of JG cells with two
      selective PDE1 inhibitors [8-methoxymethil-IBMX (8-MM-IBMX; 20 microM) and
      vinpocetine (40 microM)] and the calmodulin inhibitor W-7 (10 microM) and
      measured cAMP and renin release. Stimulation of the JG cell CaSR with the
      calcimimetic cinacalcet (1 microM) resulted in decreased cAMP from a basal of
      1.13 +/- 0.14 to 0.69 +/- 0.08 pM/mg protein (P < 0.001) and in renin release
      from 0.89 +/- 0.16 to 0.38 +/- 0.08 microg ANG I/mlxh(-1)xmg protein(-1) (P <
      0.001). However, the addition of 8-MM-IBMX with cinacalcet returned both cAMP
      (1.10 +/- 0.19 pM/mg protein) and renin (0.57 +/- 0.16 microg ANG I/mlxh(-1)xmg
      protein(-1)) to basal levels. Similar results were obtained with vinpocetine, and
      also with W-7. Combining 8-MM-IBMX and W-7 had no additive effect. To determine
      which PDE1 isoform is involved, we performed Western blot analysis for PDE1A, B,
      and C. Only Western blot analysis for PDE1C showed a characteristic band apparent
      at 80 kDa. Immunofluorescence showed cytoplasmic distribution of PDE1C and renin
      in the JG cells. In conclusion, PDE1C is expressed in isolated JG cells, and
      contributes to calcium's inhibitory modulation of renin release from JG cells.

PMID- 19741057
TI  - Site-specific attenuation of food intake but not the latency to eat after
      hypothalamic injections of neuropeptide Y in dehydrated-anorexic rats.
AB  - Anorexia that accompanies cellular dehydration in rats (DE-anorexia) offers a
      relatively simple model for investigating the functional organization of neural
      mechanisms that can suppress feeding during dehydration. Previous studies
      strongly suggest that the inputs that drive ingestive behavior control neurons in
      the paraventricular nucleus of the hypothalamus (PVH) and lateral hypothalamic
      area (LHA) remain active during DE-anorexia. Here we examine whether these two
      regions retain their sensitivity to neuropeptide Y (NPY). NPY is an important
      component in two major feeding-related inputs from the arcuate nucleus and the
      hindbrain. We found that intake responses to NPY injections in the LHA and PVH
      were suppressed in DE-anorexia, but the PVH remained less sensitive to the
      effects of NPY than the LHA in DE-anorexic animals. Indeed the higher dose of NPY
      (238 pmol) completely overcame shorter periods of DE-anorexia when injected into
      the LHA but not the PVH. However, the latency to eat after NPY injections
      remained unchanged from control animals, regardless of NPY dose, injection
      location, or intensity of anorexia. Furthermore, the onset and size of the strong
      and rapidly induced compensatory feeding that follows the return of water to DE
      anorexic animals was also unaffected by any NPY injections. These data support
      the hypothesis that DE-anorexia develops as a consequence of the premature
      termination of regularly initiated meals, which perhaps involves processes that
      alter the sensitivity of satiety mechanisms downstream to the PVH and LHA.

PMID- 19741058
TI  - Characterization of gene-activated human acid-beta-glucosidase: crystal
      structure, glycan composition, and internalization into macrophages.
AB  - Gaucher disease, the most common lysosomal storage disease, can be treated with
      enzyme replacement therapy (ERT), in which defective acid-beta-glucosidase
      (GlcCerase) is supplemented by a recombinant, active enzyme. The X-ray structures
      of recombinant GlcCerase produced in Chinese hamster ovary cells (imiglucerase,
      Cerezyme) and in transgenic carrot cells (prGCD) have been previously solved. We
      now describe the structure and characteristics of a novel form of GlcCerase under
      investigation for the treatment of Gaucher disease, Gene-Activated human
      GlcCerase (velaglucerase alfa). In contrast to imiglucerase and prGCD,
      velaglucerase alfa contains the native human enzyme sequence. All three
      GlcCerases consist of three domains, with the active site located in domain III.
      The distances between the carboxylic oxygens of the catalytic residues, E340 and
      E235, are consistent with distances proposed for acid-base hydrolysis. Kinetic
      parameters (K(m) and V(max)) of velaglucerase alfa and imiglucerase, as well as
      their specific activities, are similar. However, analysis of glycosylation
      patterns shows that velaglucerase alfa displays distinctly different structures
      from imiglucerase and prGCD. The predominant glycan on velaglucerase alfa is a
      high-mannose type, with nine mannose units, while imiglucerase contains a
      chitobiose tri-mannosyl core glycan with fucosylation. These differences in
      glycosylation affect cellular internalization; the rate of velaglucerase alfa
      internalization into human macrophages is at least 2-fold greater than that of
      imiglucerase.

PMID- 19741059
TI  - Clinical efficacy of direct DNA sequencing analysis on sputum specimens for early
      detection of drug-resistant Mycobacterium tuberculosis in a clinical setting.
AB  - BACKGROUND: Early detection of drug-resistant Mycobacterium tuberculosis is
      important for the control and prevention of disease transmission. However,
      conventional drug susceptibility tests for drug-resistant M tuberculosis take at
      least 3 to 8 weeks. Here, we report the clinical efficacy of direct DNA
      sequencing analysis for detecting drug-resistant TB on sputum specimens in a
      clinical setting. METHODS: A total of 113 sputum specimens from 111 patients, who
      were suspected of having drug-resistant TB by clinicians, were used for DNA
      sequencing of katG, rpoB, embB, and pncA genes for isoniazid (INH), rifampin
      (RIF), ethambutol (EMB), and pyrazinamide (PZA) resistance, respectively, and the
      results were compared with drug susceptibility tests. The optimization of
      antituberculosis drugs according to the results of DNA sequencing and the
      treatment outcomes of the patients were also analyzed. RESULTS: Turnaround time
      of the direct DNA sequencing analysis was 3.8 +/- 1.8 days. We found mutations
      related to drug resistance in 30 clinical specimens for katG, 39 for rpoB, 13 for
      embB, and 24 for pncA. The sensitivity and specificity of the assay were 63.6%
      and 94.6% for INH, 96.2 and 93.9% for RIF, 69.2% and 97.5% for EMB, and 100% and
      92.6% for PZA, respectively. Of the patients with RIF resistance, including
      multidrug-resistant TB by the assay, 92.5% of the patients with initial first
      line antituberculosis drugs were changed to second-line antituberculosis drugs,
      and treatment was successful in 61.9% of these cases. CONCLUSION: Direct DNA
      sequencing analysis of clinical sputum specimens is a rapid and useful method for
      the detection and treatment of drug-resistant TB.

PMID- 19741060
TI  - Performance of American Thoracic Society-recommended spirometry reference values
      in a multiethnic sample of adults: the multi-ethnic study of atherosclerosis
      (MESA) lung study.
AB  - BACKGROUND: The American Thoracic Society recommends race-specific spirometric
      reference values from the National Health and Nutrition Survey (NHANES) III for
      clinical evaluation of pulmonary function in whites, African-Americans, and
      Mexican-Americans in the United States and a correction factor of 0.94 for Asian
      Americans. We aimed to validate the NHANES III reference equations and the
      correction factor for Asian-Americans in an independent, multiethnic sample of US
      adults. METHODS: The Multi-Ethnic Study of Atherosclerosis (MESA) recruited self
      identified non-Hispanic white, African-American, Hispanic, and Asian-American
      participants aged 45 to 84 years at six US sites. The MESA-Lung Study assessed
      prebronchodilator spirometry among 3,893 MESA participants who performed
      acceptable tests, of whom 1,068 were asymptomatic healthy nonsmokers who
      performed acceptable spirometry. RESULTS: The 1,068 participants were mean age 65
      +/- 10 years, 60% female, 25% white, 20% African-American, 23% Hispanic, and 32%
      Asian-American. Observed values of FEV(1), FEV(6), and FVC among whites, African
      Americans, and Hispanics of Mexican origin in MESA-Lung were slightly lower than
      predicted values based on NHANES III. Observed values among Hispanics of non
      Mexican origin were consistently lower. Agreement in classification of
      participants with airflow obstruction based on lower limit of normal criteria was
      good (overall kappa = 0.88). For Asian-Americans, a correction factor of 0.88 was
      more accurate than 0.94. CONCLUSIONS: The NHANES III reference equations are
      valid for use among older adults who are white, African-American, or Hispanic of
      Mexican origin. Comparison of white and Asian-American participants suggests that
      a correction factor of 0.88, applied to the predicted and lower limits of normal
      values, is more appropriate than the currently recommended value of 0.94.

PMID- 19741061
TI  - VEGF gene haplotypes are associated with sarcoidosis.
AB  - BACKGROUND: The cause of sarcoidosis is unclear. Evidence suggests that there is
      a genetic susceptibility toward the disease. In this study, we examined whether
      haplotypes of vascular endothelial growth factor (VEGF) and its receptors VEGFR-1
      and VEGFR-2 are associated with the onset or the course of sarcoidosis. METHODS:
      Three hundred white patients with sarcoidosis and 381 matched controls were
      included. Sixty-three haplotype-tagging single nucleotide polymorphisms (SNPs) in
      the VEGF and VEGFR-1 and VEGFR-2 genes were selected from the HapMap Project
      phase 2. Mass spectrometry-based SNP genotyping was performed. RESULTS:
      Sarcoidosis, in general, was significantly associated with three SNPs in the
      VEGFR-1 gene: rs7337610 (P = .041), rs2296283 (P = .034), and rs12858139 (P =
      .027). In an acute course (defined as less than two episodes in a lifetime or a
      course lasting less than 2 years), an association of three SNPs in the VEGF gene
      was observed: rs833060 (P = .004), rs833068 (P = .008), and rs3025000 (P = .012).
      In the VEGFR-2 gene, one SNP was associated with an acute course of sarcoidosis
      (rs7667298, P = .023), whereas two SNPs were associated with a chronic course of
      sarcoidosis: rs7691507 (P = .029) and rs2125489 (P = .024). We then performed a
      haplotype analysis. After permutation-based correction, no significant haplotype
      association for the VEGF receptors was observed. However, we found two haplotypes
      associated with the onset of sarcoidosis in the VEGF gene. Even after correction
      for multiple testing, we obtained a P value of .0388. Moreover, patients with a
      chronic course of the disease showed a P value of .0103 for the same haplotype.
      CONCLUSIONS: There is strong evidence that VEGF and its receptors are involved in
      the onset of sarcoidosis and influence its course.

PMID- 19741062
TI  - Efficacy and safety of low dose recombinant tissue-type plasminogen activator for
      the treatment of acute pulmonary thromboembolism: a randomized, multicenter,
      controlled trial.
AB  - BACKGROUND: Optimal dosing of the recombinant tissue-type plasminogen activator
      (rt-PA) is important in treating pulmonary thromboembolism (PTE). The aim of this
      study was to compare the efficacy and safety of a 50 mg/2 h rt-PA regimen with a
      100 mg/2 h rt-PA regimen in patients with acute PTE. METHODS: A prospective,
      randomized, multicenter trial was conducted in which 118 patients with acute PTE
      and either hemodynamic instability or massive pulmonary artery obstruction were
      randomly assigned to receive a treatment regiment of either rt-PA at 50 mg/2 h (n
      = 65) or 100 mg/2 h (n = 53). The efficacy was determined by observing the
      improvements of right ventricular dysfunctions (RVDs) on echocardiograms, lung
      perfusion defects on ventilation perfusion lung scans, and pulmonary artery
      obstructions on CT angiograms. The adverse events, including death, bleeding, and
      PTE recurrence, were also evaluated. RESULTS: Progressive improvements in RVDs,
      lung perfusion defects, and pulmonary artery obstructions were found to be
      similarly significant in both treatment groups. This is true for patients with
      either hemodynamic instability or massive pulmonary artery obstruction. Three
      (6%) patients in the rt-PA 100 mg/2 h group and one (2%) in the rt-PA 50 mg/2 h
      group died as the result of either PTE or bleeding. Importantly, the 50 mg/2 h rt
      PA regimen resulted in less bleeding tendency than the 100 mg/2 h regimen (3% vs
      10%), especially in patients with a body weight < 65 kg (14.8% vs 41.2%, P =
      .049). No fatal recurrent PTE was found in either group. CONCLUSIONS: Compared
      with the 100 mg/2 h regimen, the 50 mg/2 h rt-PA regimen exhibits similar
      efficacy and perhaps better safety in patients with acute PTE. These findings
      support the notion that optimizing rt-PA dosing is worthwhile when treating
      patients with PTE. TRIAL REGISTRATION: clinicaltrials.gov; Identifier:
      NCT00781378.

PMID- 19741063
TI  - Altered surfactant protein-A expression in type II pneumocytes in COPD.
AB  - BACKGROUND: Pulmonary surfactant protein A (SP-A) is a lectin, with multiple
      functions that contribute to innate host defense and the regulation of the
      inflammatory process in the lung. In normal conditions, SP-A seems to protect
      against the effects of smoking. However, studies in smokers with or without COPD
      are limited. METHODS: Western blots on lung tissue specimens from 60 male
      subjects (32 patients with COPD, 18 smokers without COPD, and 10 control
      nonsmokers) for SP-A and the housekeeping protein actin were carried out.
      Additionally, the SP-A expression pattern was evaluated by immunohistochemistry
      in formalin-fixed, paraffin-embedded lung tissue sections from the same subjects.
      RESULTS: Western blots revealed significantly higher SP-A levels in control
      nonsmokers (4.8 +/- 0.05) when compared with patients with COPD (0.6 +/- 0.7) and
      smokers without COPD (2.4 +/- 0.9), (P < .05). However, differences that were not
      statistically significant were observed in SP-A levels among the patients with
      COPD and the smokers without COPD (P = .12). The immunohistochemical examinations
      showed an increase in the overall number of type II pneumocytes per high-power
      field in patients with COPD, but a decreased ratio of SP-A positive type II
      pneumocytes to total type II pneumocytes, compared with smokers without COPD (P =
      .001). This ratio was also correlated with FEV(1) (percent predicted [% pred]),
      (r = 0.490, P = .001). The overall number of alveolar macrophages per high-power
      field was significantly higher in patients with COPD compared with smokers
      without COPD (P = .001). The ratio of SP-A positive alveolar macrophages was
      increased in patients with COPD when compared with smokers without COPD (P =
      .002), while this was correlated with airway obstruction (FEV(1), % pred) (r =
      0.281, P = .04). CONCLUSIONS: Our results indicate that altered SP-A expression
      could be another link to COPD pathogenesis and highlights the need for further
      studies on surfactant markers in COPD.

PMID- 19741064
TI  - Prospective study to determine the volume of pleural fluid required to diagnose
      malignancy.
AB  - BACKGROUND: The optimal volume of pleural fluid to diagnose a malignant effusion
      is unknown. Our study was designed to demonstrate if a minimum pleural fluid
      volume (10 mL) is equivalent to a large volume thoracentesis to make a
      cytopathologic diagnosis of malignancy. METHODS: A total of 121 thoracentesis
      samples were obtained from 102 patients with suspected or known malignant
      effusions. Pleural fluid was collected in three aliquots for cytologic
      examination (10 mL, 60 mL, > or = 150 mL). The pathologist was blinded to patient
      identifiers and aliquot volume. Sensitivity, specificity, negative predictive
      value (NPV), and positive predictive value (PPV) were calculated for each volume
      for the diagnosis of malignancy. RESULTS: Pleural malignancy was diagnosed in 90
      patient encounters (74.4%). For direct smear/cytospin, there was increased
      sensitivity and NPV for 60 mL (P = .0058 and P = .045, respectively) and for > or
      = 150 mL (P < .001 and P = .009, respectively) compared with 10 mL. For combined
      direct smear/cytospin and cell block preparations, statistical significance for
      sensitivity and NPV existed only between the 10 mL and > or = 150 mL specimens (P
      = .0099 and P = .033, respectively). No statistical difference existed for
      specificity or PPV for any aliquot volume. CONCLUSIONS: The sensitivity for
      diagnosis of pleural malignancy is dependent on the pleural fluid volume
      extracted during thoracentesis. Volumes of 10 mL do not perform as well as larger
      volumes. When both direct smear/cytospin and cell block preparations are used, we
      recommend > or = 150 mL, whereas when only direct smear/cytospin is used, 60 mL
      is adequate for the diagnosis a malignant pleural effusion.

PMID- 19741065
TI  - Single amino acid changes in the turnip mosaic virus viral genome-linked protein
      (VPg) confer virulence towards Arabidopsis thaliana mutants knocked out for
      eukaryotic initiation factors eIF(iso)4E and eIF(iso)4G.
AB  - Previous resistance analyses of Arabidopsis thaliana mutants knocked out for
      eukaryotic translation initiation factors showed that disruption of the At
      eIF(iso)4E or both the At-eIF(iso)4G1 and At-eIF(iso)4G2 genes resulted in
      resistance against turnip mosaic virus (TuMV). This study selected TuMV virulent
      variants that overcame this resistance and showed that two independent mutations
      in the region coding for the viral genome-linked protein (VPg) were sufficient to
      restore TuMV virulence in At-eIF(iso)4E and At-eIF(iso)4G1xAt-eIF(iso)4G2
      knockout plants. As a VPg-eIF(iso)4E interaction has been shown previously to be
      critical for TuMV infection, a systematic analysis of the interactions between A.
      thaliana eIF4Es and VPgs of virulent and avirulent TuMVs was performed. The
      results suggest that virulent TuMV variants may use an eIF4F-independent pathway.

PMID- 19741066
TI  - Genomics and evolution of Aedes-borne flaviviruses.
AB  - We analysed the complete coding sequences of all recognized species of Aedes
      borne flavivirus, including previously uncharacterized viruses within the yellow
      fever virus (YFV), Spondweni virus (SPOV) and dengue virus (DENV) groups. Two
      major phylogenetic lineages were revealed: one included the YFV and Entebbe bat
      virus groups, and the other included the DENV, SPOV and Culex-borne flavivirus
      groups. This analysis supported previous evidence that Culex-borne flaviviruses
      have evolved from ancestral Aedes-borne viruses. However, the topology at the
      junction between these lineages remains complex and may be refined by the
      discovery of viruses related to the Kedougou virus. Additionally, viral evolution
      was found to be associated with the appearance of new biological characteristics;
      mutations that may modify the envelope protein structure were identified for
      seven viruses within the YFV group, and an expansion of host-vector range was
      identified in the two major evolutionary lineages, which in turn may facilitate
      the emergence of mosquito-borne flaviviruses.

PMID- 19741067
TI  - Assembly and export determine the intracellular distribution of hepatitis B virus
      core protein subunits.
AB  - Little is known about the parameters and factors that determine the intracellular
      distribution of the hepatitis B virus core protein (HBc). In order to study HBc
      in living cells, HBc was tagged with green fluorescent protein (GFP). Being
      assembly-incompetent, the GFP-fusion protein was distributed equally throughout
      the cell. Mutational inactivation of known serine-phosphorylation sites within
      the C-terminal region led to predominantly intranuclear localization.
      Phosphorylation of these targets, presumably by an SR domain protein kinase,
      resulted in a predominantly cytoplasmic localization, which suggests active
      cytoplasmic export or retention. The phosphoserine itself, and not its negative
      charge, appears essential for the underlying mechanism. In addition, the arginine
      rich, protamine-like domain surrounding these phosphorylation sites does not
      function as the dominant nuclear-localization signal, as had been assumed
      previously, because neither deleting nor altering these sequences led to a change
      in intracellular HBc subunit distribution. Restoring the capability of the fusion
      protein to form capsids by co-assembly with assembly-competent, sterically
      uncompromised HBc subunits provided a second assay that gave insight into the
      effects resulting from capsid formation. Assembly was found to be the dominant
      factor in the cytoplasmic retention of the GFP-HBc fusion protein. Furthermore,
      the stability of these empty capsids was influenced by the cell-cycle inhibitor
      nocodazole. Thus, the intracellular distribution of HBc is dominated by
      cytoplasmic assembly, which is supported by the active nuclear export of HBc
      subunits, and modulated during the cell cycle by the instability of capsids.

PMID- 19741068
TI  - Rat respiratory coronavirus infection: replication in airway and alveolar
      epithelial cells and the innate immune response.
AB  - The rat coronavirus sialodacryoadenitis virus (SDAV) causes respiratory infection
      and provides a system for investigating respiratory coronaviruses in a natural
      host. A viral suspension in the form of a microspray aerosol was delivered by
      intratracheal instillation into the distal lung of 6-8-week-old Fischer 344 rats.
      SDAV inoculation produced a 7 % body weight loss over a 5 day period that was
      followed by recovery over the next 7 days. SDAV caused focal lesions in the lung,
      which were most severe on day 4 post-inoculation (p.i.). Immunofluorescent
      staining showed that four cell types supported SDAV virus replication in the
      lower respiratory tract, namely Clara cells, ciliated cells in the bronchial
      airway and alveolar type I and type II cells in the lung parenchyma. In bronchial
      alveolar lavage fluid (BALF) a neutrophil influx increased the population of
      neutrophils to 45 % compared with 6 % of the cells in control samples on day 2
      after mock inoculation. Virus infection induced an increase in surfactant protein
      SP-D levels in BALF of infected rats on days 4 and 8 p.i. that subsided by day
      12. The concentrations of chemokines MCP-1, LIX and CINC-1 in BALF increased on
      day 4 p.i., but returned to control levels by day 8. Intratracheal instillation
      of rats with SDAV coronavirus caused an acute, self-limited infection that is a
      useful model for studying the early events of the innate immune response to
      respiratory coronavirus infections in lungs of the natural virus host.

PMID- 19741069
TI  - Comparison of three reference methods for testing susceptibility of staphylococci
      to trimethoprim-sulfamethoxazole.
AB  - Three reference MIC methods approved by the Clinical and Laboratory Standards
      Institute were compared by testing 567 staphylococci against trimethoprim
      sulfamethoxazole. Category agreement ranged from 94.9% (broth macrodilution
      versus broth microdilution) to 98.6% (agar dilution versus broth microdilution).
      Twenty-seven strains resistant by broth macrodilution were susceptible by broth
      microdilution.

PMID- 19741070
TI  - Transmission of an extended-spectrum-beta-lactamase-producing Escherichia coli
      (sequence type ST131) strain between a father and daughter resulting in septic
      shock and Emphysematous pyelonephritis.
AB  - Probable transmission of an extended-spectrum-beta-lactamase-producing
      Escherichia coli strain (sequence type ST131) between a father and daughter was
      documented. The father developed severe, recurrent pyelonephritis with multiple
      small abscesses; the daughter later developed septic shock, bacteremia, and
      extensive emphysematous pyelonephritis. This multidrug-resistant E. coli clone
      appears to be highly pathogenic and transmissible.

PMID- 19741071
TI  - Phylogenetic analysis of human parvovirus b19 sequences from eleven different
      countries confirms the predominance of genotype 1 and suggests the spread of
      genotype 3b.
AB  - Phylogenetic analysis of 166 human parvovirus B19 sequences from 11 different
      countries attributed 91.57% to genotype 1, 5.42% to genotype 3b, and 3.01% to
      genotype 3a. Very similar viruses of genotype 1 circulated widely in Europe and
      Israel. Genotype 3b seems to show an increasing spread outside of Africa.

PMID- 19741072
TI  - False-positive PCR detection of Tropheryma whipplei in cerebrospinal fluid and
      biopsy samples from a child with chronic lymphocytic meningitis.
AB  - We report the case of a teenager with chronic lymphocytic meningitis for whom
      Tropheryma whipplei 16S rRNA PCR results were positive in two cerebrospinal fluid
      samples and one duodenal biopsy specimen. PCR targeting another specific sequence
      of Tropheryma whipplei and sequencing of the initially amplified 16S rRNA
      fragment did not confirm the results.

PMID- 19741073
TI  - Breathing new life into pneumonia diagnostics.

PMID- 19741074
TI  - Infections with VIM-1 metallo-{beta}-lactamase-producing enterobacter cloacae and
      their correlation with clinical outcome.
AB  - The aim of this study was to ascertain the incidence and clinical significance of
      metallo-beta-lactamases among Enterobacter strains isolated from patients with
      nosocomial infections. We prospectively collected data on patients with
      Enterobacter infection during a 13-month period. All of the strains were
      investigated for antibiotic susceptibility, the presence and expression of
      metallo-beta-lactamases, and clonality. Of 29 infections (11 involving the
      urinary tract, 7 pneumonias, 3 skin/soft tissue infections, 3 intra-abdominal
      infections, 3 bacteremias, and 2 other infections), 7 (24%) were caused by
      Enterobacter cloacae strains harboring a bla(VIM-1) gene associated or not with a
      bla(SHV12) gene. Infections caused by VIM-1-producing strains were more
      frequently associated with a recent prior hospitalization (P = 0.006), cirrhosis
      (P = 0.03), relapse of infection (P < 0.001), and more prolonged duration of
      antibiotic therapy (P = 0.01) than were other infections. All of the isolates
      were susceptible to imipenem and meropenem and had bla(VIM-1) preceded by a weak
      P1 promoter and inactivated P2 promoters. Most VIM-1-producing Enterobacter
      isolates belonged to a main clone, but four different clones were found.
      Multiclonal VIM-1-producing E. cloacae infections are difficult to diagnose due
      to an apparent susceptibility to various beta-lactams, including carbapenems, and
      are associated with a high relapse rate and a more prolonged duration of
      antibiotic therapy.

PMID- 19741075
TI  - Clinical relevance of the recently described species Aeromonas aquariorum.
AB  - Twenty-two human extraintestinal isolates (11 from blood) and three isolates
      recovered from patients with diarrhea were genetically characterized as Aeromonas
      aquariorum, a novel species known only from ornamental fish. The isolates proved
      to bear a considerable number of virulence genes, and all were resistant to
      amoxicillin (amoxicilline), cephalothin (cefalotin), and cefoxitin. Biochemical
      differentiation from the most relevant clinical species is provided.

PMID- 19741076
TI  - Rapid SYBR green I and modified probe real-time reverse transcription-PCR assays
      identify influenza H1N1 viruses and distinguish between pandemic and seasonal
      strains.
AB  - A rapid SYBR green I real-time reverse transcription-PCR (RT-PCR) assay was
      developed to identify pandemic influenza H1N1 virus from clinical specimens in
      less than 1 h. Probe real-time RT-PCR influenza A/B, H1/H3, and swNP/swHA assays
      were modified into the same PCR program, which allows for rapid and simultaneous
      typing and subtyping of influenza viruses.

PMID- 19741077
TI  - EuroCareCF quality assessment of diagnostic microbiology of cystic fibrosis
      isolates.
AB  - The identification of microbial species from respiratory specimens and their
      susceptibility to antimicrobial agents are among the most important diagnostic
      measures of care for patients with cystic fibrosis (CF). Under the umbrella of
      EuroCareCF, two quality assurance trials of CF microbiology were performed in
      2007 and 2008. Nine formulations with CF bacterial isolates were dispatched. A
      total of 31/37 laboratories from 18/21 European countries participated in the
      2007 and 2008 trials. The common CF pathogens Pseudomonas aeruginosa and
      Staphylococcus aureus were correctly identified by almost all participants in
      both trials, even if the strains presented uncommon phenotypes. Burkholderia
      cenocepacia IIIB and Burkholderia vietnamensis CF isolates, however, were
      correctly assigned to the species level by only 26% and 27% of the laboratories,
      respectively. Emerging pathogens such as Achromobacter xylosoxidans, Inquilinus
      limosus, and Pandoraea pnomenusa were also not detected or were misclassified by
      many laboratories. One participant correctly identified all CF isolates in both
      trials. The percentages of correct classifications (susceptible, intermediate,
      resistant) by antimicrobial susceptibility testing ranged from 55 to 100%
      (median, 96%) per isolate and drug. The shortcomings in the diagnostics of rare
      and emerging pathogens point to the need for continuing education in CF
      microbiology and suggest the establishment of CF microbiology reference
      laboratories.

PMID- 19741078
TI  - The EmsB tandemly repeated multilocus microsatellite: a new tool to investigate
      genetic diversity of Echinococcus granulosus sensu lato.
AB  - Cystic echinococcosis (CE) is a widespread and severe zoonotic disease caused by
      infection with the larval stage of the eucestode Echinococcus granulosus sensu
      lato. The polymorphism exhibited by nuclear and mitochondrial markers
      conventionally used for the genotyping of different parasite species and strains
      does not reach the level necessary for the identification of genetic variants
      linked to restricted geographical areas. EmsB is a tandemly repeated multilocus
      microsatellite that proved its usefulness for the study of genetic polymorphisms
      within the species E. multilocularis, the causative agent of alveolar
      echinococcosis. In the present study, EmsB was used to characterize E. granulosus
      sensu lato samples collected from different host species (sheep, cattle,
      dromedaries, dogs, and human patients) originating from six different countries
      (Algeria, Mauritania, Romania, Serbia, Brazil, and the People's Republic of
      China). The conventional mitochondrial cox1 and nad1 markers identified genotypes
      G1, G3, G5, G6, and G7, which are clustered into three groups corresponding to
      the species E. granulosus sensu stricto, E. ortleppi, and E. canadensis. With the
      same samples, EmsB provided a higher degree of genetic discrimination and
      identified variations that correlated with the relatively small-scale geographic
      origins of the samples. In addition, one of the Brazilian single hydatid cysts
      presented a hybrid genotypic profile that suggested genetic exchanges between E.
      granulosus sensu stricto and E. ortleppi. In summary, the EmsB microsatellite
      exhibits an interesting potential for the elaboration of a detailed map of the
      distribution of genetic variants and therefore for the determination and tracking
      of the source of CE.

PMID- 19741079
TI  - Preliminary evaluation of the BrEMA1 gene as a tool for associating babesia rossi
      genotypes and clinical manifestation of canine Babesiosis.
AB  - Babesia rossi, an intraerythrocytic protozoan, causes a severe, often life
      threatening disease of domestic dogs. Dogs treated early for B. rossi infection
      usually recover from the disease, but dogs left untreated or treated at a later
      stage of infection seldom survive. Dogs infected with B. rossi have varied
      clinical manifestations that can be categorized as uncomplicated (with a good
      prognosis) or complicated (with a poor prognosis). One hundred twenty-one blood
      samples were collected from dogs presented to the Onderstepoort Veterinary
      Academic Hospital and diagnosed with babesiosis by the use of a thin blood smear.
      An additional 20 samples were obtained from Babesia-infected dogs from private
      clinics around the Onderstepoort, Johannesburg, Durban, White River, and Cape
      Town areas. The samples were screened by PCR targeting the Babesia rossi
      erythrocyte membrane antigen gene (BrEMA1) and by sequencing of the polymorphic
      region (i.e., region with a variable number of hexapeptide repeats). Analysis of
      PCR products revealed 11 different gene profiles, visualized by gel
      electrophoresis. Twelve distinct BrEMA1 genotypes were identified by sequencing,
      but the numbers of hexapeptide repeats varied from 6 to 31 (classified as
      genotype6 to genotype31). The genotypes were retrospectively compared to the
      clinical case data. The most frequently encountered B. rossi parasites were those
      attributed to genotype19 (36.2%), genotype28 and genotype29 (20.6% each), and
      genotype11 (12.7%). These genotypes were also the ones associated with the
      poorest prognosis. This preliminary finding suggests clinically important
      differences between the various B. rossi genotypes identified.

PMID- 19741080
TI  - Multicenter evaluation of a transcription-reverse transcription concerted assay
      for rapid detection of mycobacterium tuberculosis complex in clinical specimens.
AB  - A European multicenter study was performed to evaluate the performance of a new
      method, based on the transcription-reverse transcription concerted reaction (TRC
      2), which enabled one-step amplification and real-time detection of the
      Mycobacterium tuberculosis 16S rRNA target directly in clinical specimens. A
      total of 633 respiratory and nonrespiratory specimens were tested, and the
      results were compared with those from smears and cultures. A total of 129
      patients (Paris center) were followed up in order to evaluate the clinical
      performance of TRC-2. By using M. tuberculosis complex strains to inoculate
      sterile sputa, the detection limit of TRC-2 was found to be 30 to 50 CFU/ml. A
      total of 548 respiratory specimens and 59 extrapulmonary specimens were
      assessable. For pulmonary specimens, the sensitivities of TRC-2 and acid-fast
      smear were 86.8% and 50.4%, respectively (P = 0.002). The specificities were
      97.5% and 100%, respectively. For extrapulmonary specimens, the sensitivities of
      TRC-2 and acid-fast smear were 83.3% and 8.3% (P < 0.0001), and the specificities
      were 95.8% and 100%, respectively. Fifteen of 129 patients were diagnosed with
      pulmonary tuberculosis (TB). The sensitivities of culture and TRC-2 were 80%
      (12/15) and 86.7% (13/15) (P = 0.16), and the specificities were 100% and 93.9%,
      respectively. Based on an 11.6% incidence of TB in our population, the positive
      predictive values of TRC-2 and culture were 81.3% and 100%, respectively, and the
      negative predictive values were 98.2% and 97.4%, respectively. These results
      demonstrated that detection of M. tuberculosis complex in clinical specimens by
      TRC-2 with ready-to-use reagents was an efficient and rapid method for the
      diagnosis of pulmonary and extrapulmonary TB.

PMID- 19741081
TI  - Comparison of real-time PCR and conventional biochemical methods for
      identification of Staphylococcus lugdunensis.
AB  - Staphylococcus lugdunensis is an aggressive, virulent member of the coagulase
      negative staphylococci (CoNS) that is responsible for severe, rapidly progressive
      skin and soft tissue infections and native valve endocarditis. To facilitate
      prompt identification and appropriate therapy, we describe here a rapid and
      robust multiplex real-time PCR assay that is able to definitively distinguish S.
      lugdunensis from other staphylococci. Using melting curve analysis, the assay
      also identifies Staphylococcus aureus and CoNS other than S. lugdunensis and
      determines MecA-dependent resistance to methicillin (meticillin). When applied to
      a panel of well-characterized staphylococcal reference strains, as well as 165
      clinical isolates previously identified by conventional methods, the assay was
      both sensitive and specific for S. lugdunensis, correctly identifying the
      reference strain and all 47 S. lugdunensis isolates without inappropriate
      amplification of other staphylococci. Furthermore, rapid biochemical
      identification using the WEE-TAB system to detect ornithine decarboxylase
      activity was found to be unsuitable as an alternative to PCR identification,
      displaying just 31% sensitivity and 77% specificity when tested on a subset (90
      isolates) of the clinical strains. We therefore propose that this simple,
      accurate PCR approach will allow for the routine and timely identification of S.
      lugdunensis in the clinical microbiology laboratory.

PMID- 19741082
TI  - Comparison of a commercial multiplex real-time PCR to the cell cytotoxicity
      neutralization assay for diagnosis of clostridium difficile infections.
AB  - A commercial multiplex real-time PCR assay (Cepheid Xpert C. difficile assay) for
      the diagnosis of Clostridium difficile infection was evaluated. The sensitivity
      and specificity of the Cepheid assay were 97.1% and 93.0% for fresh stools, using
      the cell cytotoxicity neutralization assay as the reference. Using PCR ribotyping
      as the reference for ribotype 027 strains, the corresponding figures were 100%
      and 98.1%, respectively.

PMID- 19741083
TI  - Molecular characteristics of German G8P[4] rotavirus strain GER1H-09 suggest that
      a genotyping and subclassification update is required for G8.
AB  - A rare G8P[4] rotavirus, designated GER1H-09, was detected in a stool sample from
      an infant suffering from repeated episodes of emesis for 2 days without diarrhea.
      Sequencing of all genomic RNA segments was performed, and complete coding
      sequences were determined. The VP7 amino acid sequence revealed a close
      phylogenetic relationship to human G8P[6] and G8P[8] isolates from Slovenia and
      Africa. GER1H-09 shared typical amino acid residues within variable regions VR3
      to VR7 with those strains, and their subclassification as lineage G8-II
      rotaviruses is proposed. The variability in VR3 was identified as the likely
      reason for the failure in genotyping G8-II rotaviruses by commonly used multiplex
      PCR. Furthermore, the sequences of associated structural and nonstructural
      proteins showed high amino acid identities to DS-1-like rotaviruses. The genotype
      composition of GER1H-09 (G8-P[4]-I2-R2-C2-M2-A2-N2-T2-E2-H2) suggests the
      occurrence of reassortment events between G8 genotypes and human DS-1-like G2P[4]
      rotaviruses.

PMID- 19741084
TI  - Diagnostic assay recommended by the world health organization for swine origin
      influenza a (h1n1) virus cross-reacts with H5N1 influenza virus.

PMID- 19741086
TI  - Multicenter evaluation of Bactec MGIT 960 system for second-line drug
      susceptibility testing of Mycobacterium tuberculosis complex.
AB  - The Bactec MGIT 960 system for testing susceptibility to second-line drugs was
      evaluated with 117 clinical strains in a multicenter study. The four drugs
      studied were levofloxacin, amikacin, capreomycin, and ethionamide. The critical
      concentration established for levofloxacin and amikacin was 1.5 microg/ml, that
      established for capreomycin was 3.0 microg/ml, and that established for
      ethionamide was 5.0 microg/ml. The overall level of agreement between the agar
      proportion method and the MGIT 960 system was 96.4%, and the levels of agreement
      for the individuals drugs were 99.1% for levofloxacin, 100% for amikacin, 97.4%
      for capreomycin, and 88.9% for ethionamide. The rate of reproducibility of the
      drug susceptibility testing results between the participating laboratories was
      99.5%.

PMID- 19741085
TI  - Development and validation of a multiplex real-time PCR assay for simultaneous
      genotyping and human T-lymphotropic virus type 1, 2, and 3 proviral load
      determination.
AB  - The human T-lymphotropic virus (HTLV) proviral load remains the best surrogate
      marker for disease progression. Real-time PCR techniques have been developed for
      detection and quantification of cosmopolitan HTLV type 1a (HTLV-1a) and HTLV-2.
      Since a growing level of diversity in subtypes and genotypes is observed, we
      developed a multiplex quantitative PCR for simultaneous detection, genotyping,
      and quantification of proviral loads of HTLV-1, 2, and 3. Our assay uses tax type
      specific primers and dually labeled probes and has a dynamic range of 10(5) to 10
      HTLV copies. One hundred sixty-three samples were analyzed, among which all of
      the different subtypes within each HTLV genotype could be detected. The
      performance of proviral load determination of our multiplex assay was compared
      with that of a previously published HTLV-1 singleplex quantitative PCR based on
      SYBR green detection, developed at a different institute. Linear regression
      analysis showed a statistically significant (P < 0.0001) and strong (r(2) = 0.87)
      correlation between proviral load values measured with the two distinct real-time
      PCR assays. In conclusion, our novel assay offers an accurate molecular diagnosis
      and genotyping, together with the determination of the proviral load of HTLV
      infected individuals, in a single amplification reaction. Moreover, our molecular
      assay could offer an alternative when current available serological assays are
      insufficient.

PMID- 19741087
TI  - Salmonella enterica serotype 4,5,12:i:-, an emerging Salmonella serotype that
      represents multiple distinct clones.
AB  - The prevalence, among human clinical cases, of Salmonella enterica serotype
      4,5,12:i:-, a serotype antigenically similar to Salmonella enterica serotype
      Typhimurium but lacking second-phase flagellar antigens, has increased
      considerably over the last 10 years. To probe the evolution and ecology of this
      emerging serotype, we characterized 190 Salmonella isolates initially classified
      as Salmonella serotypes 4,5,12:i:- (n = 90) and Typhimurium (n = 100) and
      obtained from various sources in the United States and Spain. These isolates were
      characterized into six sequence types (determined by multilocus sequence typing
      [MLST]) and 79 pulsed-field gel electrophoresis types. The majority of Salmonella
      serotype 4,5,12:i:- and Typhimurium isolates (85 and 84 isolates, respectively)
      represented a single MLST type. Existing genome information revealed different
      genome deletions (which included genes responsible for phase 2 flagellum
      expression) in four Spanish Salmonella serotype 4,5,12:i:- isolates and one U.S.
      Salmonella serotype 4,5,12:i:- isolate. Fifty-nine isolates of both serotypes,
      representing different sources and geographical locations as well as different
      molecular subtypes, were thus screened for the presence of six genes and one
      specific region, all of which were previously found to show variable presence
      among Salmonella serotype 4,5,12:i:- and Typhimurium strains. All Salmonella
      serotype 4,5,12:i:- isolates lacked the phase 2 flagella genes fljA and fljB,
      which were present in all Salmonella serotype Typhimurium isolates. While all
      Spanish Salmonella serotype 4,5,12:i:- isolates carried the same deletion
      surrounding fljAB, all but two U.S. isolates showed a different genomic deletion;
      the two atypical U.S. isolates represented the "Spanish" deletion genotype and a
      unique deletion genotype. Salmonella serotype 4,5,12:i:- thus appears to
      represent at least two common clones, which cannot easily be differentiated with
      standard diagnostic procedures.

PMID- 19741088
TI  - Comparison of BD phoenix to vitek 2, microscan MICroSTREP, and Etest for
      antimicrobial susceptibility testing of Streptococcus pneumoniae.
AB  - The performance of the BD Phoenix Automated Microbiology System (BD Diagnostic
      Systems) was compared to those of the Vitek 2 (bioMerieux), the MicroScan
      MICroSTREP plus (Siemens), and Etest (bioMerieux) for antibiotic susceptibility
      tests (AST) of 311 clinical isolates of Streptococcus pneumoniae. The overall
      essential agreement (EA) between each test system and the reference microdilution
      broth reference method for S. pneumoniae AST results was >95%. For Phoenix, the
      EAs of individual antimicrobial agents ranged from 90.4% (clindamycin) to 100%
      (vancomycin and gatifloxacin). The categorical agreements (CA) of Phoenix, Vitek
      2, MicroScan, and Etest for penicillin were 95.5%, 94.2%, 98.7%, and 97.7%,
      respectively. The overall CA for Phoenix was 99.3% (1 very major error [VME] and
      29 minor errors [mEs]), that for Vitek 2 was 98.8% (7 VMEs and 28 mEs), and those
      for MicroScan and Etest were 99.5% each (19 and 13 mEs, respectively). The
      average times to results for Phoenix, Vitek 2, and the manual methods were 12.1
      h, 9.8 h, and 24 h, respectively. From these data, the Phoenix AST results
      demonstrated a high degree of agreement with all systems evaluated, although
      fewer VMEs were observed with the Phoenix than with the Vitek 2. Overall, both
      automated systems provided reliable AST results for the S. pneumoniae-antibiotic
      combinations in half the time required for the manual methods, rendering them
      more suitable for the demands of expedited reporting in the clinical setting.

PMID- 19741089
TI  - Direct 16S rRNA gene sequencing from clinical specimens, with special focus on
      polybacterial samples and interpretation of mixed DNA chromatograms.
AB  - RipSeq (iSentio, Bergen, Norway) is a web-based application for the analysis of
      mixed DNA chromatograms. It opens the possibility to analyze chromatograms
      obtained by direct 16S rRNA gene sequencing from polybacterial human clinical
      samples. In this study, we used direct 16S rRNA gene sequencing to investigate
      264 samples from a wide range of suspected human bacterial infections. The
      sequence-based identification was compared with the results from routine culture
      based identification. A total of 151 samples were positive by the first PCR,
      producing 85 pure and 66 mixed DNA chromatograms. All mixed chromatograms were
      analyzed by RipSeq, although seven were so complex that only the dominant
      bacterial sequences could be identified. In general, sequence-based
      identification detected a larger number of species than did culture for samples
      from patients who had received antibiotics prior to sample collection and for
      samples containing anaerobic bacteria. RipSeq made it possible to apply this
      supplementary diagnostic tool to typical polybacterial specimens, such as
      internal abscesses, pleural fluids, and bile.

PMID- 19741090
TI  - Salmonella enterica serovar Typhi-specific immunoglobulin A antibody responses in
      plasma and antibody in lymphocyte supernatant specimens in Bangladeshi patients
      with suspected typhoid fever.
AB  - Many currently available diagnostic tests for typhoid fever lack sensitivity
      and/or specificity, especially in areas of the world where the disease is
      endemic. In order to identify a diagnostic test that better correlates with
      typhoid fever, we evaluated immune responses to Salmonella enterica serovar Typhi
      (serovar Typhi) in individuals with suspected typhoid fever in Dhaka, Bangladesh.
      We enrolled 112 individuals with suspected typhoid fever, cultured day 0 blood
      for serovar Typhi organisms, and performed Widal assays on days 0, 5, and 20. We
      harvested peripheral blood lymphocytes and analyzed antibody levels in
      supernatants collected on days 0, 5, and 20 (using an antibody-in-lymphocyte
      supernatant [ALS] assay), as well as in plasma on these days. We measured ALS
      reactivity to a serovar Typhi membrane preparation (MP), a formalin-inactivated
      whole-cell preparation, and serovar Typhi lipopolysaccharide. We measured
      responses in healthy Bangladeshi, as well as in Bangladeshi febrile patients with
      confirmed dengue fever or leptospirosis. We categorized suspected typhoid fever
      individuals into different groups (groups I to V) based on blood culture results,
      Widal titer, and clinical features. Responses to MP antigen in the immunoglobulin
      A isotype were detectable at the time of presentation in the plasma of 81% of
      patients. The ALS assay, however, tested positive in all patients with documented
      or highly suspicious typhoid, suggesting that such a response could be the basis
      of improved diagnostic point-of-care-assay for serovar Typhi infection. It can be
      important for use in epidemiological studies, as well as in difficult cases
      involving fevers of unknown origin.

PMID- 19741091
TI  - Differentiation of larva migrans caused by Baylisascaris procyonis and Toxocara
      species by Western blotting.
AB  - Baylisascaris procyonis and Toxocara species are two important causes of larva
      migrans in humans. Larva migrans caused by Toxocara spp. is well known and is
      diagnosed serologically by enzyme immunoassay. Over a dozen cases of larva
      migrans and associated eosinophilic encephalitis caused by B. procyonis have also
      been reported, and at least a dozen additional cases are known. An enzyme-linked
      immunosorbent assay (ELISA) using the excretory-secretory (ES) antigen of B.
      procyonis larvae is currently being used in our laboratory as an aid in the
      diagnosis of this infection in humans. Clinically affected individuals show very
      high reactivity (measured as the optical density) on this ELISA; however, a one
      way cross-reactivity with Toxocara spp. has been observed. As an approach to
      differentiate these two infections based on serology, we performed Western blots,
      wherein the B. procyonis ES antigen was reacted with serum samples from
      individuals known to be positive for either Toxocara spp. or B. procyonis larva
      migrans. Western blot results showed that B. procyonis antigens of between 30 and
      45 kDa were specifically identified only by the sera from individuals with
      Baylisascaris larva migrans, thus allowing for differentiation between the two
      infections. This included human patient serum samples submitted for serologic
      testing, as well as sera from rabbits experimentally infected with B. procyonis.
      When used in conjunction with the ELISA, Western blotting could be an efficient
      tool for diagnosis of this infection in humans.

PMID- 19741092
TI  - Physical and functional interaction of transmembrane thioredoxin-related protein
      with major histocompatibility complex class I heavy chain: redox-based protein
      quality control and its potential relevance to immune responses.
AB  - In the endoplasmic reticulum (ER), a variety of oxidoreductases classified in the
      thioredoxin superfamily have been found to catalyze the formation and
      rearrangement of disulfide bonds. However, the precise function and specificity
      of the individual thioredoxin family proteins remain to be elucidated. Here, we
      characterize a transmembrane thioredoxin-related protein (TMX), a membrane-bound
      oxidoreductase in the ER. TMX exists in a predominantly reduced form and
      associates with the molecular chaperon calnexin, which can mediate substrate
      binding. To determine the target molecules for TMX, we apply a substrate-trapping
      approach based on the reaction mechanism of thiol-disulfide exchange, identifying
      major histocompatibility complex (MHC) class I heavy chain (HC) as a candidate
      substrate. Unlike the classical ER oxidoreductases such as protein disulfide
      isomerase and ERp57, TMX seems not to be essential for normal assembly of MHC
      class I molecules. However, we show that TMX-class I HC interaction is enhanced
      during tunicamycin-induced ER stress, and TMX prevents the ER-to-cytosol
      retrotranslocation of misfolded class I HC targeted for proteasomal degradation.
      These results suggest a specific role for TMX and its mechanism of action in
      redox-based ER quality control.

PMID- 19741093
TI  - HOPS interacts with Apl5 at the vacuole membrane and is required for consumption
      of AP-3 transport vesicles.
AB  - Adaptor protein complexes (APs) are evolutionarily conserved heterotetramers that
      couple cargo selection to the formation of highly curved membranes during vesicle
      budding. In Saccharomyces cerevisiae, AP-3 mediates vesicle traffic from the late
      Golgi to the vacuolar lysosome. The HOPS subunit Vps41 is one of the few proteins
      reported to have a specific role in AP-3 traffic, yet its function remains
      undefined. We now show that although the AP-3 delta subunit, Apl5, binds Vps41
      directly, this interaction occurs preferentially within the context of the HOPS
      docking complex. Fluorescence microscopy indicates that Vps41 and other HOPS
      subunits do not detectably colocalize with AP-3 at the late Golgi or on post
      Golgi (Sec7-negative) vesicles. Vps41 and HOPS do, however, transiently
      colocalize with AP-3 vesicles when these vesicles dock at the vacuole membrane.
      In cells with mutations in HOPS subunits or the vacuole SNARE Vam3, AP-3 shifts
      from the cytosol to a membrane fraction. Fluorescence microscopy suggests that
      this fraction consists of post-Golgi AP-3 vesicles that have failed to dock or
      fuse at the vacuole membrane. We propose that AP-3 remains associated with budded
      vesicles, interacts with Vps41 and HOPS upon vesicle docking at the vacuole, and
      finally dissociates during docking or fusion.

PMID- 19741094
TI  - Cdc42 regulates Fc gamma receptor-mediated phagocytosis through the activation
      and phosphorylation of Wiskott-Aldrich syndrome protein (WASP) and neural-WASP.
AB  - Cdc42 is a key regulator of the actin cytoskeleton and activator of Wiskott
      Aldrich syndrome protein (WASP). Although several studies have separately
      demonstrated the requirement for both Cdc42 and WASP in Fc(gamma) receptor
      (Fc(gamma)R)-mediated phagocytosis, their precise roles in the signal cascade
      leading to engulfment are still unclear. Reduction of endogenous Cdc42 expression
      by using RNA-mediated interference (short hairpin RNA [shRNA]) severely impaired
      the phagocytic capacity of RAW/LR5 macrophages, due to defects in phagocytic cup
      formation, actin assembly, and pseudopod extension. Addition of wiskostatin, a
      WASP/neural-WASP (N-WASP) inhibitor showed extensive inhibition of phagocytosis,
      actin assembly, and cell extension identical to the phenotype seen upon reduction
      of Cdc42 expression. However, using WASP-deficient bone marrow-derived
      macrophages or shRNA of WASP or N-WASP indicated a requirement for both WASP and
      N-WASP in phagocytosis. Cdc42 was necessary for WASP/N-WASP activation, as
      determined using a conformation-sensitive antibody against WASP/N-WASP and
      partial restoration of phagocytosis in Cdc42 reduced cells by expression of a
      constitutively activated WASP. In addition, Cdc42 was required for proper WASP
      tyrosine phosphorylation, which was also necessary for phagocytosis. These
      results indicate that Cdc42 is essential for the activation of WASP and N-WASP,
      leading to actin assembly and phagocytic cup formation by macrophages during
      Fc(gamma)R-mediated phagocytosis.

PMID- 19741095
TI  - Unbalancing the phosphatidylinositol-4,5-bisphosphate-cofilin interaction impairs
      cell steering.
AB  - Cofilin is a key player in actin dynamics during cell migration. Its activity is
      regulated by (de)phosphorylation, pH, and binding to phosphatidylinositol-4,5
      bisphosphate [PI(4,5)P(2)]. Here, we here use a human cofilin-1 (D122K) mutant
      with increased binding affinity for PI(4,5)P(2) and slower release from the
      plasma membrane to study the role of the PI(4,5)P(2)-cofilin interaction in
      migrating cells. In fibroblasts in a background of endogenous cofilin, D122K
      cofilin expression negatively affects cell turning frequency. In carcinoma cells
      with down-regulated endogenous cofilin, D122K cofilin neither rescues the drastic
      morphological defects nor restores the effects in cell turning capacity, unlike
      what has been reported for wild-type cofilin. In cofilin knockdown cells, D122K
      cofilin expression promotes outgrowth of an existing lamellipod in response to
      epidermal growth factor (EGF) but does not result in initiation of new
      lamellipodia. This indicates that, next to phospho- and pH regulation, the normal
      release kinetics of cofilin from PI(4,5)P(2) is crucial as a local activation
      switch for lamellipodia initiation and as a signal for migrating cells to change
      direction in response to external stimuli. Our results demonstrate that the
      PI(4,5)P(2) regulatory mechanism, that is governed by EGF-dependent phospholipase
      C activation, is a determinant for the spatial and temporal control of cofilin
      activation required for lamellipodia initiation.

PMID- 19741096
TI  - Mitochondrial ubiquitin ligase MITOL ubiquitinates mutant SOD1 and attenuates
      mutant SOD1-induced reactive oxygen species generation.
AB  - We have previously identified a novel mitochondrial ubiquitin ligase, MITOL,
      which is localized in the mitochondrial outer membrane and is involved in the
      control of mitochondrial dynamics. In this study, we examined whether MITOL
      eliminates misfolded proteins localized to mitochondria. Mutant superoxide
      dismutase1 (mSOD1), one of misfolded proteins, has been shown to localize in
      mitochondria and induce mitochondrial dysfunction, possibly involving in the
      onset and progression of amyotrophic lateral sclerosis. We found that in the
      mitochondria, MITOL interacted with and ubiquitinated mSOD1 but not wild-type
      SOD1. In vitro ubiquitination assay revealed that MITOL directly ubiquitinates
      mSOD1. Cycloheximide-chase assay in the Neuro2a cells indicated that MITOL
      overexpression promoted mSOD1 degradation and suppressed both the mitochondrial
      accumulation of mSOD1 and mSOD1-induced reactive oxygen species (ROS) generation.
      Conversely, the overexpression of MITOL CS mutant and MITOL knockdown by specific
      siRNAs resulted in increased accumulation of mSOD1 in mitochondria, which
      enhanced mSOD1-induced ROS generation and cell death. Thus, our findings indicate
      that MITOL plays a protective role against mitochondrial dysfunction caused by
      the mitochondrial accumulation of mSOD1 via the ubiquitin-proteasome pathway.

PMID- 19741097
TI  - Myosin Vc is a molecular motor that functions in secretory granule trafficking.
AB  - Class V myosins are actin-based motor proteins that have critical functions in
      organelle trafficking. Of the three class V myosins expressed in mammals,
      relatively little is known about Myo5c except that it is abundant in exocrine
      tissues. Here we use MCF-7 cells to identify the organelles that Myo5c associates
      with, image the dynamics of Myo5c in living cells, and test the functions of
      Myo5c. Endogenous Myo5c localizes to two distinct compartments: small puncta and
      slender tubules. Myo5c often exhibits a highly polarized distribution toward the
      leading edge in migrating cells and is clearly distinct from the Myo5a or Myo5b
      compartments. Imaging with GFP-Myo5c reveals that Myo5c puncta move slowly
      (approximately 30 nm/s) and microtubule independently, whereas tubules move
      rapidly (approximately 440 nm/s) and microtubule dependently. Myo5c puncta
      colocalize with secretory granule markers such as chromogranin A and Rab27b,
      whereas Myo5c tubules are labeled by Rab8a. TIRF imaging indicates that the
      granules can be triggered to undergo secretion. To test if Myo5c functions in
      granule trafficking, we used the Myo5c tail as a dominant negative and found that
      it dramatically perturbs the distribution of granule markers. These results
      provide the first live-cell imaging of Myo5c and indicate that Myo5c functions in
      secretory granule trafficking.

PMID- 19741098
TI  - Adaptation to visuomotor rotation through interaction between posterior parietal
      and motor cortical areas.
AB  - Studying how motor adaptation to visuomotor rotation for one reach direction
      generalizes to other reach directions can provide insight into how visuomotor
      maps are represented and learned in the brain. Previous psychophysical studies
      have concluded that postadaptation generalization is restricted to a narrow range
      of directions around the training direction. A population-coding model that
      updates the weights between narrow Gaussian-tuned visual units and motor units on
      each trial reproduced experimental trial-by-trial learning curves for rotation
      adaptation and the generalization function measured postadaptation. These results
      suggest that the neurons involved in rotation adaptation have a relatively narrow
      directional tuning width ( approximately 23 degrees ). Population coding models
      with units having broader tuning functions (such as cosine tuning in motor cortex
      and Gaussian sum in the cerebellum) could not reproduce the narrow single-peaked
      generalization pattern. Visually selective neurons with narrow Gaussian tuning
      curves have been identified in posterior parietal cortex, making it a possible
      site of adaptation to visuomotor rotation. We propose that rotation adaptation
      proceeds through changes in synaptic weights between neurons in posterior
      parietal cortex and motor cortex driven by a prediction error computed by the
      cerebellum.

PMID- 19741099
TI  - Brain switch for reflex micturition control detected by FMRI in rats.
AB  - The functions of the lower urinary tract are controlled by complex pathways in
      the brain that act like switching circuits to voluntarily or reflexly shift the
      activity of various pelvic organs (bladder, urethra, urethral sphincter, and
      pelvic floor muscles) from urine storage to micturition. In this study,
      functional magnetic resonance imaging (fMRI) was used to visualize the brain
      switching circuits controlling reflex micturition in anesthetized rats. The fMRI
      images confirmed the hypothesis based on previous neuroanatomical and
      neurophysiological studies that the brain stem switch for reflex micturition
      control involves both the periaqueductal gray (PAG) and the pontine micturition
      center (PMC). During storage, the PAG was activated by afferent input from the
      urinary bladder while the PMC was inactive. When bladder volume increased to the
      micturition threshold, the switch from storage to micturition was associated with
      PMC activation and enhanced PAG activity. A complex brain network that may
      regulate the brain stem micturition switch and control storage and voiding was
      also identified. Storage was accompanied by activation of the motor cortex,
      somatosensory cortex, cingulate cortex, retrosplenial cortex, thalamus, putamen,
      insula, and septal nucleus. On the other hand, micturition was associated with:
      1) increased activity of the motor cortex, thalamus, and putamen; 2) a shift in
      the locus of activity in the cingulate and insula; and 3) the emergence of
      activity in the hypothalamus, substantia nigra, globus pallidus, hippocampus, and
      inferior colliculus. Understanding brain control of reflex micturition is
      important for elucidating the mechanisms underlying neurogenic bladder
      dysfunctions including frequency, urgency, and incontinence.

PMID- 19741100
TI  - Transformation in the neural code for whisker deflection direction along the
      lemniscal pathway.
AB  - A prominent characteristic of neurons in the whisker system is their selectivity
      to the direction in which a whisker is deflected. The aim of this study was to
      determine how information about whisker direction is encoded at successive levels
      of the lemniscal pathway. We made extracellular recordings under identical
      conditions from the trigeminal ganglion, ventro-posterior medial thalamus (VPM),
      and barrel cortex while varying the direction of whisker deflection. We found a
      marked increase in the variability of single unit responses along the pathway. To
      study the consequences of this for information processing, we quantified the
      responses using mutual information. VPM units conveyed 48% of the mutual
      information conveyed by ganglion units, and cortical units conveyed 12%. The
      fraction of neuronal bandwidth used for transmitting direction information
      decreased from 40% in the ganglion to 24% in VPM and 5% in barrel cortex. To test
      whether, in cortex, population coding might compensate for this information loss,
      we made simultaneous recordings. We found that cortical neuron pairs conveyed 2.1
      times the mutual information conveyed by single neurons. Overall, these findings
      indicate a marked transformation from a subcortical neural code based on small
      numbers of reliable neurons to a cortical code based on populations of unreliable
      neurons. However, the basic form of the neural code in ganglion, thalamus, and
      cortex was similar-at each stage, the first poststimulus spike carried the
      majority of the information.

PMID- 19741101
TI  - Differential activation of projection neurons by two sensory pathways contributes
      to motor pattern selection.
AB  - Sensorimotor integration is known to occur at the level of motor circuits as well
      as in upstream interneurons that regulate motor activity. Here we show, using the
      crab stomatogastric nervous system (STNS) as a model, that different sensory
      systems affect the same set of projection neurons. However, they have
      qualitatively different effects on their activities (excitation vs. inhibition),
      and these differences contribute to the selection of motor patterns from
      multifunctional circuits. We compare the actions of the proprioceptive anterior
      gastric receptor (AGR) and the inferior ventricular (IV) neurons, which relay
      chemosensory information from the brain to the STNS, on modulatory commissural
      neurons 1 and 5 (MCN1 and MCN5) and commissural projection neuron 2 (CPN2) and
      their resulting actions on the gastric mill central pattern generating circuit in
      the stomatogastric ganglion. When stimulated, AGR and the IV neurons affect all
      three projection neurons but elicit distinct gastric mill rhythms. The effects of
      both sensory pathways on the projection neurons differ in the type of excitation
      provided to CPN2 and MCN5 (electrical vs. chemical) and the effect on MCN1
      (direct inhibition by AGR vs. polysynaptic excitation by the IV neurons). The
      latter is functionally important because a restoration of MCN1 activity during
      the AGR rhythm made it more similar to that elicited by IV neuron stimulation.
      Our results thus support the hypothesis that sensory pathways activate different
      combinations of projection neurons to select distinct outputs from the same
      neuronal circuit.

PMID- 19741102
TI  - Experience-dependent intrinsic plasticity in interneurons of barrel cortex layer
      IV.
AB  - It is unclear whether intrinsic excitabilities of specific interneurons are
      modulated by sensory experiences. Here, I examined the intrinsic excitabilities
      of interneurons in "sensory-spared" and "sensory-deprived" cortices of GAD67-GFP
      mice. The results showed that whisker trimming, begun at postnatal day 7 for 3
      wk, induced significant changes in intrinsic and firing properties of fast
      spiking (FS) but not regular spiking nonpyramidal (RSNP) cells. Firing threshold,
      spike frequency, spike adaptation index, and input resistance of FS cells were
      significantly altered by sensory deprivation such that FS cells became less
      excitable. An up-regulation of IA currents in FS cells appeared to be
      responsible. Along with changes in the intrinsic properties of FS cells, whisker
      trimming also induced a robust reduction in the number of vesicular glutamate
      transporter 2 positive varicosities and parvalbumin expression and the strength
      of thalamocortical (TC) excitatory postsynaptic currents in FS cells in the
      "sensory-deprived barrels." The probability of spike induction by TC stimulus was
      reduced by 30% and the spike jitter was increased in sensory-deprived FS cells.
      These results suggest that the FS networks are selectively inhibited by sensory
      deprivation. The concurrent changes of intrinsic properties and expression of
      parvalbumin in FS but not RSNP cells with TC synapses support a contribution from
      the TC pathway and glutamate to sensory-induced activity-dependent intrinsic
      plasticity of inhibitory networks in barrel cortex.

PMID- 19741103
TI  - Direct activation and temporal response properties of rabbit retinal ganglion
      cells following subretinal stimulation.
AB  - In the last decade several groups have been developing vision prostheses to
      restore visual perception to the profoundly blind. Despite some promising results
      from human trials, further understanding of the neural mechanisms involved is
      crucial for improving the efficacy of these devices. One of the techniques
      involves placing stimulating electrodes in the subretinal space between the
      photoreceptor layer and the pigment epithelium to evoke neural responses in the
      degenerative retina. This study used cell-attached and whole cell current-clamp
      recordings to investigate the responses of rabbit retinal ganglion cells (RGCs)
      following subretinal stimulation with 25-mum-diameter electrodes. We found that
      direct RGC responses with short latency (</=2 ms using 0.1-ms pulses) could be
      reliably elicited. The thresholds for these responses were reported for on, off,
      and on-off RGCs over pulse widths 0.1-5.0 ms. During repetitive stimulation these
      direct activation responses were more readily elicited than responses arising
      from stimulation of the retinal network. The temporal spiking characteristics of
      RGCs were characterized as a function of stimulus configurations. We found that
      the response profiles could be generalized into four classes with distinctive
      properties. Our results suggest that for subretinal vision prostheses short
      pulses are preferable for efficacy and safety considerations, and that direct
      activation of RGCs will be necessary for reliable activation during high
      frequency stimulation.

PMID- 19741104
TI  - Maintenance of thalamic epileptiform activity depends on the astrocytic glutamate
      glutamine cycle.
AB  - The generation of prolonged neuronal activity depends on the maintenance of
      synaptic neurotransmitter pools. The astrocytic glutamate-glutamine cycle is a
      major mechanism for recycling the neurotransmitters GABA and glutamate. Here we
      tested the effect of disrupting the glutamate-glutamine cycle on two types of
      neuronal activity patterns in the thalamus: sleep-related spindles and
      epileptiform oscillations. In recording conditions believed to induce glutamine
      scarcity, epileptiform oscillations showed a progressive reduction in duration
      that was partially reversible by the application of exogenous glutamine (300
      muM). Blocking uptake of glutamine into neurons with alpha-(methylamino)
      isobutyric acid (5 mM) caused a similar reduction in oscillation duration, as did
      blocking neuronal GABA synthesis with 3-mercaptoproprionic acid (10 muM).
      However, comparable manipulations did not affect sleep spindles. Together, these
      results support a crucial role for the glutamate-glutamine cycle in providing the
      neurotransmitters necessary for the generation of epileptiform activity and
      suggest potential therapeutic approaches that selectively reduce seizure activity
      but maintain normal neuronal activity.

PMID- 19741106
TI  - On the open-loop and feedback processes that underlie the formation of
      trajectories during visual and nonvisual locomotion in humans.
AB  - We investigated the nature of the control mechanisms at work during goal-oriented
      locomotion. In particular, we tested the effects of vision, locomotor speed, and
      the presence of via points on the geometric and kinematic properties of locomotor
      trajectories. We first observed that the average trajectories recorded in visual
      and nonvisual locomotion were highly comparable, suggesting the existence of
      vision-independent processes underlying the formation of locomotor trajectories.
      Then by analyzing and comparing the variability around the average trajectories
      across different experimental conditions, we were able to demonstrate the
      existence of on-line feedback control in both visual and nonvisual locomotion and
      to clarify the relations between visual and nonvisual control strategies. Based
      on these insights, we designed a model in which maximum-smoothness and optimal
      feedback control principles account, respectively, for the open-loop and feedback
      processes. Taken together, the experimental and modeling findings provide a novel
      understanding of the nature of the motor, sensory, and "navigational" processes
      underlying goal-oriented locomotion.

PMID- 19741105
TI  - Locomotor adaptation and aftereffects in patients with reduced somatosensory
      input due to peripheral neuropathy.
AB  - We studied 12 peripheral neuropathy patients (PNP) and 13 age-matched controls
      with the "broken escalator" paradigm to see how somatosensory loss affects gait
      adaptation and the release and recovery ("braking") of the forward trunk
      overshoot observed during this locomotor aftereffect. Trunk displacement, foot
      contact signals, and leg electromyograms (EMGs) were recorded while subjects
      walked onto a stationary sled (BEFORE trials), onto the moving sled (MOVING or
      adaptation trials), and again onto the stationary sled (AFTER trials). PNP were
      unsteady during the MOVING trials, but this progressively improved, indicating
      some adaptation. During the after trials, 77% of control subjects displayed a
      trunk overshoot aftereffect but over half of the PNP (58%) did not. The PNP
      without a trunk aftereffect adapted to the MOVING trials by increasing distance
      traveled; subsequently this was expressed as increased distance traveled during
      the aftereffect rather than as a trunk overshoot. This clear separation in
      consequent aftereffects was not seen in the normal controls suggesting that, as a
      result of somatosensory loss, some PNP use distinctive strategies to negotiate
      the moving sled, in turn resulting in a distinct aftereffects. In addition, PNP
      displayed earlier than normal anticipatory leg EMG activity during the first
      after trial. Although proprioceptive inputs are not critical for the emergence or
      termination of the aftereffect, somatosensory loss induces profound changes in
      motor adaptation and anticipation. Our study has found individual differences in
      adaptive motor performance, indicative that PNP adopt different feed-forward gait
      compensatory strategies in response to peripheral sensory loss.

PMID- 19741107
TI  - Bilateral limb phase relationship and its potential to alter muscle activity
      phasing during locomotion.
AB  - It is well established that the sensorimotor state of one limb can influence
      another limb and therefore bilateral somatosensory inputs make an important
      contribution to interlimb coordination patterns. However, the relative
      contribution of interlimb pathways for modifying muscle activation patterns in
      terms of phasing is less clear. Here we studied adaptation of muscle activity
      phasing to the relative angular positions of limbs using a split-crank ergometer,
      where the cranks could be decoupled to allow different spatial angular position
      relationships. Twenty neurologically healthy individuals performed the specified
      pedaling tasks at different relative angular positions while surface
      electromyographic (EMG) signals were recorded bilaterally from eight lower
      extremity muscles. During each experiment, the relative angular crank positions
      were altered by increasing or decreasing their difference by randomly ordered
      increments of 30 degrees over the complete cycle [0 degrees (in phase pedaling);
      30, 60, 90, 120, 150, and 180 degrees (standard pedaling); and 210, 240, 270,
      300, and 330 degrees out of phase pedaling]. We found that manipulating the
      relative angular positions of limbs in a pedaling task caused muscle activity
      phasing changes that were either delayed or advanced, dependent on the relative
      spatial position of the two cranks and this relationship is well-explained by a
      sine curve. Further, we observed that the magnitude of phasing changes in
      biarticular muscles (like rectus femoris) was significantly greater than those of
      uniarticular muscles (like vastus medialis). These results are important because
      they provide new evidence that muscle phasing can be systematically influenced by
      interlimb pathways.

PMID- 19741109
TI  - Functional properties of cutaneous A- and C-fibers 1-15 months after a nerve
      lesion.
AB  - The functional properties of cutaneous afferent fibers were investigated 1-15 mo
      after nerve lesions, which allowed regeneration into denervated skin. After
      crushing or transection and resuturing the rat sural nerve, ongoing activity and
      responses to cold, heat, and mechanical stimuli presented to the denervated skin
      or to the nerve distal to the lesion were examined in 273 A-fibers and 211 C
      fibers. Reinnervation of skin by A-fibers was largely complete by 1-4 mo after
      crushing but incomplete after transection and resuturing. A few A-fibers could be
      activated from the nerve trunk, even after 10-15 mo. Almost all regenerated A
      fibers were mechanosensitive and about 6% were cold- or heat-sensitive. A few A
      fibers had ongoing activity after nerve crush. Only 15-35% of C-fibers could be
      activated at 1-4 mo, but 60% were excited from the skin at 10-15 mo, when many
      also had receptive fields within the lesioned nerve. The remaining C-fibers had
      receptive fields only within the nerve trunk. Responses of both intraneural and
      intradermal endings of C-fibers could be classified into functional groups
      similar to those of C-fibers in control nerves to cutaneous stimuli. The
      frequency of afferent C-fibers with ongoing activity that were not highly cold
      sensitive was 45%. We conclude that the functional characteristics of afferent A-
      and C-fibers are expressed by regenerating nerve endings, even when they do not
      reinnervate their target tissue. The reinnervation of skin by afferent C-fibers
      is extremely slow and may never recover to normal.

PMID- 19741108
TI  - Postural feedback scaling deficits in Parkinson's disease.
AB  - Many differences in postural responses have been associated with age and
      Parkinson's disease (PD), but until now there has been no quantitative model to
      explain these differences. We developed a feedback control model of body dynamics
      that could reproduce the postural responses of young subjects, elderly subjects,
      and subjects with PD, and we investigated whether the postural impairments of
      subjects with PD can be described as an abnormal scaling of postural feedback
      gain. Feedback gains quantify how the nervous system generates compensatory joint
      torques based on kinematic responses. Seven subjects in each group experienced
      forward postural perturbations to seven different backward support surface
      translations ranging from 3- to 15-cm amplitudes and with a constant duration of
      275 ms. Ground reaction forces and joint kinematics were measured to obtain joint
      torques from inverse dynamics. A full-state feedback controller with a two
      segment body dynamic model was used to simulate joint kinematics and kinetics in
      response to perturbations. Results showed that all three subject groups gradually
      scaled postural feedback gains as a function of perturbation amplitudes, and the
      scaling started even before the maximum allowable ankle torque was reached. This
      result implies that the nervous system takes body dynamics into account and
      adjusts postural feedback gains to accommodate biomechanical constraints. PD
      subjects showed significantly smaller than normal ankle feedback gain with low
      scaling and larger hip feedback gain, which led to an early violation of the flat
      foot constraint and unusually small (bradykinetic) postural responses. Our
      postural feedback control model quantitatively described the postural abnormality
      of the patients with PD as abnormal feedback gains and reduced ability to modify
      postural feedback gain with changes in postural challenge.

PMID- 19741110
TI  - Is apoptosis the cause of noninsertional achilles tendinopathy?
AB  - BACKGROUND: The pathogenesis of chronic tendinopathy is unclear but it does not
      appear to be an inflammatory process. Apoptosis may lead to degenerate tissue
      through a nitric oxide-mediated pathway. Increased levels of nitric oxide have
      been demonstrated in Achilles tendinopathy. HYPOTHESIS: Nitric oxide-mediated
      apoptosis is an important mechanism in the development of Achilles tendinopathy.
      STUDY DESIGN: Controlled laboratory study. METHODS: Samples were obtained from
      the Achilles tendons of 14 patients with noninsertional Achilles tendinopathy.
      Control samples were taken from macroscopically normal tendon correlating with
      areas of normal tissue on magnetic resonance imaging. Immunohistochemical
      techniques identified the expression of inducible and endothelial nitric oxide
      synthase as markers of nitric oxide production. Apoptotic cells were identified
      using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling
      (TUNEL) and the demonstration of caspase-3 activation. RESULTS: Significant
      differences were found between the diseased tendon and the controls for all
      parameters. The mean caspase-3 cell count for diseased tendon was 51.9 versus
      28.3 for the controls (P < .001). The mean TUNEL cell count for diseased tendon
      was 24.1 compared with 14.8 (P < .001). Inducible nitric oxide synthase (iNOS)
      densitometry revealed a mean of 26.1 for the diseased tissue versus 15.0 for the
      controls (P < .001) and the values for endothelial nitric oxide synthase (eNOS)
      were 48.3 and 23.7, respectively (P = .015). CONCLUSION: Apoptosis may play a
      role in the development of noninsertional Achilles tendinopathy and appears to be
      related to the presence of raised eNOS and iNOS levels. CLINICAL RELEVANCE: A
      clearer understanding of the tendinopathic process may lead to new treatment
      strategies aimed at modulating apoptosis.

PMID- 19741111
TI  - What is the optimal postconditioning algorithm?
AB  - Ischemic postconditioning has emerged as a clinically feasible intervention for
      limiting infarction in the setting of percutaneous intervention. In ischemic
      postconditioning, a number of cycles of a brief period of reperfusion followed by
      a brief period of occlusion are applied immediately upon reperfusion of the
      ischemic heart. Although ischemic postconditioning is protective in both animals
      and man, the animal studies reveal that the algorithm used in selecting the
      duration of the occlusion and reperfusion periods is critical to the degree of
      protection realized and it varies with species. The question then arises what is
      the best algorithm for man? The available animal and clinical data are examined
      in an attempt to shed light on this perplexing problem.

PMID- 19741112
TI  - Use of and satisfaction with sources of health information among older Internet
      users and nonusers.
AB  - PURPOSE: Older adults generally have an increased need for health care
      information. Whereas some use the Internet to look for this information, others
      use more traditional sources. This study gathered data from older adults to
      determine their health information needs, the perceived usefulness of sources of
      health information, and if there are differences in perceptions and use of health
      information between Internet users and nonusers. DESIGN AND METHODS: We conducted
      9 focus groups-4 groups of Internet users (n = 27) and 5 groups of non-Internet
      users (n = 26)-to determine reasons for seeking health information, satisfaction
      with information, and use of the Internet to fulfill information needs. Data from
      focus groups were supplemented with questionnaire data. RESULTS: Those who do not
      use the Internet were found to be just as satisfied with the health information
      they find as those who search for information online. We also found that nonusers
      are more likely to make health care decisions based upon information found
      offline than Internet users who have access to more information. IMPLICATIONS:
      Nonusers may find it quicker to look for information through traditional media
      sources and stay offline, thus limiting their information options. Strategies for
      encouraging Internet use and programs to teach effective searching skills are
      needed. Physicians could also direct older patients toward credible health
      information Web sites.

PMID- 19741113
TI  - Netrin participates in the development of retinotectal synaptic connectivity by
      modulating axon arborization and synapse formation in the developing brain.
AB  - Netrin has been implicated in retinal ganglion cell (RGC) axon pathfinding in a
      number of species. In Xenopus laevis, RGC axons reaching their target in the
      optic tectum can be repelled by a netrin-1 gradient in vitro, suggesting that
      netrin may also function in wiring events that follow successful axon
      pathfinding. Here, we examined the contribution of netrin to RGC axon
      arborization and synapse formation at the target. Time-lapse confocal microscopy
      imaging of individual RGC axons coexpressing GFP-synaptobrevin and DsRed in the
      intact Xenopus brain demonstrated a role for deleted in colorectal cancer (DCC)
      mediated netrin signaling. Microinjection of netrin-1 into the tectum induced a
      rapid and transient increase in presynaptic site addition that resulted in higher
      presynaptic site density over a 24 h observation period. Moreover, netrin induced
      dynamic axon branching, increasing branch addition and retraction; a behavior
      that ultimately increased total branch number. In contrast, microinjection of DCC
      function-blocking antibodies prevented the increase in presynaptic site number
      normally observed in control axons as well as the associated increase in branch
      number and axon arbor growth. Dynamic analysis of axon arbors demonstrated that
      the effects of anti-DCC on axon morphology and presynaptic connectivity were
      attributable to a specific decrease in new synapse and branch additions, without
      affecting the stability of existing synapses and branches. Together, these
      results indicate that, in the absence of DCC signaling, RGC axons fail to branch
      and differentiate, and support a novel role for netrin in later phases of
      retinotectal development.

PMID- 19741114
TI  - Cannabinoid receptor activation in the basolateral amygdala blocks the effects of
      stress on the conditioning and extinction of inhibitory avoidance.
AB  - Despite the efficacy of behavior therapy for human anxiety disorders, extinction
      like treatments require repeated cue exposures and are vulnerable to reversal by
      a number of environmental factors, particularly stress. The endocannabinoid
      system has recently emerged as important in the regulation of extinction learning
      and in the regulation of the hypothalamic-pituitary-adrenal axis. Here, we aimed
      to examine the involvement of the cannabinoid CB(1) receptor in the basolateral
      amygdala (BLA) in inhibitory avoidance (IA) conditioning and extinction and to
      test whether cannabinoid activation would reverse the effects of stress on these
      memory processes. The synthetic full agonist of the CB(1)/CB(2) receptor
      WIN55,212-2 [R-(+)-(2,3-dihydro-5-methyl-3-[(4-morpholinyl)methyl]pyrol[1,2,3-de]
      1,4- benzoxazin-6-yl)(1-naphthalenyl) methanone monomethanesulfonate] (5
      microg/0.5 microl) microinjected into the BLA had no effect on IA conditioning or
      extinction by itself. However, microinjecting WIN55,212-2 into the BLA before
      exposing the rats to a stressor reversed the enhancing effects of the stressor on
      IA conditioning and its impairing effects on IA extinction. Importantly,
      WIN55,212-2 microinjected into the BLA reduced stress-induced elevations in
      corticosterone levels. Control experiments demonstrated the following: (1) the
      effects of WIN55,212-2 could not be attributed to sensorimotor deficits, because
      these parameters seemed unchanged by WIN55,212-2 microinjected into the BLA; and
      (2) the CB(1) receptor in the BLA is crucially involved in the extinction of IA,
      because the CB(1) receptor antagonist AM251 [N-1-(2,4-dichlorophenyl)-5-(4
      iodophenyl)-4-methyl-N-1-piperidinyl-1H-pyrazole-3-carboxamide] (6 ng/0.5 microl)
      microinjected into the BLA significantly blocked extinction. Together, our
      findings may support a wide therapeutic application for cannabinoids in the
      treatment of conditions associated with the inappropriate retention of aversive
      memories and stress-related disorders.

PMID- 19741115
TI  - Dopamine is necessary for cue-dependent fear conditioning.
AB  - Dopamine (DA) is implicated in many behaviors, including motor function,
      cognition, and reward processing; however, the role of DA in fear processing
      remains equivocal. To examine the role of DA in fear-related learning, dopamine
      deficient (DD) mice were tested in a fear-potentiated startle paradigm. DA
      synthesis can be restored in DD mice through administration of 3, 4-dihydroxy-l
      phenylalanine (l-Dopa), thereby permitting the assessment of fear processing in
      either a DA-depleted or -replete state. Fear-potentiated startle was absent in DD
      mice but could be restored by l-Dopa administration immediately after fear
      conditioning. Selective viral-mediated restoration of DA synthesis within the
      ventral tegmental area fully restored fear learning in DD mice, and restoration
      of DA synthesis to DA neurons projecting to the basolateral amygdala restored
      short-term memory but not long-term memory or shock sensitization. We also
      demonstrate that the DA D(1) receptor (D(1)R) and D(2)-like receptors are
      necessary for cue-dependent fear learning. These findings indicate that DA acting
      on multiple receptor subtypes within multiple target regions facilitates the
      stabilization of fear memory.

PMID- 19741116
TI  - KV7/M channels mediate osmotic modulation of intrinsic neuronal excitability.
AB  - Modest decreases in extracellular osmolarity induce brain hyperexcitability that
      may culminate in epileptic seizures. At the cellular level, moderate
      hyposmolarity markedly potentiates the intrinsic neuronal excitability of
      principal cortical neurons without significantly affecting their volume. The most
      conspicuous cellular effect of hyposmolarity is converting regular firing neurons
      to burst-firing mode. This effect is underlain by hyposmotic facilitation of the
      spike afterdepolarization (ADP), but its ionic mechanism is unknown. Because
      blockers of K(V)7 (KCNQ) channels underlying neuronal M-type K(+) currents
      (K(V)7/M channels) also cause spike ADP facilitation and bursting, we
      hypothesized that lowering osmolarity inhibits these channels. Using current- and
      voltage-clamp recordings in CA1 pyramidal cells in situ, we have confirmed this
      hypothesis. Furthermore, we show that hyposmotic inhibition of K(V)7/M channels
      is mediated by an increase in intracellular Ca(2+) concentration via release from
      internal stores but not via influx of extracellular Ca(2+). Finally, we show that
      interfering with internal Ca(2+)-mediated inhibition of K(V)7/M channels entirely
      protects against hyposmotic ADP facilitation and bursting, indicating the
      exclusivity of this novel mechanism in producing intrinsic neuronal
      hyperexcitability in hyposmotic conditions.

PMID- 19741117
TI  - Asynchronous transmitter release from cholecystokinin-containing inhibitory
      interneurons is widespread and target-cell independent.
AB  - Neurotransmitter release at most central synapses is synchronized to the timing
      of presynaptic action potentials. Here, we show that three classes of
      depolarization-induced suppression of inhibition-expressing, cholecystokinin
      (CCK)-containing, hippocampal interneurons show highly asynchronous release in
      response to trains of action potentials. This asynchrony is correlated to the
      class of presynaptic interneuron but is unrelated to their postsynaptic cell
      target. Asynchronous and synchronous release from CCK-containing interneurons
      show a slightly different calcium dependence, such that the proportion of
      asynchronous release increases with external calcium concentration, possibly
      suggesting that the modes of release are mediated by different calcium sensors.
      Asynchronous IPSCs include very large (up to 500 pA/7nS) amplitude events, which
      persist in low extracellular calcium and strontium, showing that they result from
      quantal transmitter release at single release sites. Finally, we show that
      asynchronous release is prominent in response to trains of presynaptic spikes
      that mimic natural activity of CCK-containing interneurons. That asynchronous
      release from CCK-containing interneurons is a widespread phenomenon indicates a
      fundamental role for these cells within the hippocampal network that is distinct
      from the phasic inhibition provided by parvalbumin-containing interneurons.

PMID- 19741119
TI  - Representation of goal and movements without overt motor behavior in the human
      motor cortex: a transcranial magnetic stimulation study.
AB  - We recorded motor-evoked potentials (MEPs) to transcranial magnetic stimulation
      from the right opponens pollicis (OP) muscle while participants observed an
      experimenter operating two types of pliers: pliers opened by the extension of the
      fingers and closed by their flexion ("normal pliers") and pliers opened by the
      flexion of the fingers and closed by their extension ("reverse pliers"). In one
      experimental condition, the experimenter merely opened and closed the pliers; in
      the other, he grasped an object with them. In a further condition, the
      participants imagined themselves operating the normal and reverse pliers. During
      the observation of actions devoid of a goal, the MEP amplitudes, regardless of
      pliers used, reflected the muscular pattern involved in the execution of the
      observed action. In contrast, during the observation of goal-directed actions,
      the MEPs from OP were modulated by the action goal, increasing during goal
      achievement despite the opposite hand movements necessary to obtain it. During
      motor imagery, the MEPs recorded from OP reflected the muscular pattern required
      to perform the imagined action. We propose that covert activity in the human
      motor cortex may reflect different aspects of motor behavior. Imagining oneself
      performing tool actions or observing tool actions devoid of a goal activates the
      representation of the hand movements that correspond to the observed ones. In
      contrast, the observation of tool actions with a goal incorporates the distal
      part of the tool in the observer's body schema, resulting in a higher-order
      representation of the meaning of the motor act.

PMID- 19741118
TI  - Atoh1-lineal neurons are required for hearing and for the survival of neurons in
      the spiral ganglion and brainstem accessory auditory nuclei.
AB  - Atoh1 is a basic helix-loop-helix transcription factor necessary for the
      specification of inner ear hair cells and central auditory system neurons derived
      from the rhombic lip. We used the Cre-loxP system and two Cre-driver lines
      (Egr2(Cre) and Hoxb1(Cre)) to delete Atoh1 from different regions of the cochlear
      nucleus (CN) and accessory auditory nuclei (AAN). Adult Atoh1-conditional knock
      out mice (Atoh1(CKO)) are behaviorally deaf, have diminished auditory brainstem
      evoked responses, and have disrupted CN and AAN morphology and connectivity. In
      addition, Egr2; Atoh1(CKO) mice lose spiral ganglion neurons in the cochlea and
      AAN neurons during the first 3 d of life, revealing a novel critical period in
      the development of these neurons. These new mouse models of predominantly central
      deafness illuminate the importance of the CN for support of a subset of
      peripheral and central auditory neurons.

PMID- 19741120
TI  - Multiple transcriptional mechanisms control Ptf1a levels during neural
      development including autoregulation by the PTF1-J complex.
AB  - Ptf1a, along with an E protein and Rbpj, forms the transcription factor complex
      PTF1-J that is essential for proper specification of inhibitory neurons in the
      spinal cord, retina, and cerebellum. Here we show that two highly conserved
      noncoding genomic regions, a distal 2.3 kb sequence located 13.4 kb 5' and a 12.4
      kb sequence located immediately 3' of the Ptf1a coding region, have distinct
      activity in controlling Ptf1a expression in all of these domains. The 5' 2.3 kb
      sequence functions as an autoregulatory element and directs reporter gene
      expression to all Ptf1a domains in the developing nervous system. The
      autoregulatory activity of this element was demonstrated by binding of the PTF1-J
      complex in vitro, Ptf1a localization to this genomic region in vivo, and the in
      vivo requirement of Ptf1a for the activity of the regulatory element in
      transgenic mice. In contrast, the 12.4 kb 3' regulatory region does not contain
      any conserved PTF1 sites, and its expression in transgenic mice is independent of
      Ptf1a. Thus, regulatory information for initiation of Ptf1a expression in the
      developing nervous system is located within the 12.4 kb sequence 3' of the Ptf1a
      gene. Together, these results identify multiple transcriptional mechanisms that
      control Ptf1a levels, one modulating levels by autoregulation through the PTF1-J
      complex, and the other a Ptf1a-independent mechanism for initial activation.

PMID- 19741121
TI  - Does retinotopy influence cortical folding in primate visual cortex?
AB  - In humans and other Old World primates, much of visual cortex comprises a set of
      retinotopic maps, embedded in a cortical sheet with well known, identifiable
      folding patterns. However, the relationship between these two prominent cortical
      variables has not been comprehensively studied. Here, we quantitatively tested
      this relationship using functional and structural magnetic resonance imaging in
      monkeys and humans. We found that the vertical meridian of the visual field tends
      to be represented on gyri (convex folds), whereas the horizontal meridian is
      preferentially represented in sulci (concave folds), throughout visual cortex in
      both primate species. This relationship suggests that the retinotopic maps may
      constrain the pattern of cortical folding during development.

PMID- 19741122
TI  - Non-Hebbian synaptic plasticity induced by repetitive postsynaptic action
      potentials.
AB  - Modern theories on memory storage have mainly focused on Hebbian long-term
      potentiation (LTP), which requires coincident activation of presynaptic and
      postsynaptic neurons for its induction. In addition to Hebbian LTP, the roles of
      non-Hebbian plasticity have also been predicted by some neuronal network models.
      However, still only a few pieces of evidence have been presented for the presence
      of such plasticity. In this study, we show in mouse hippocampal slices that LTP
      can be induced by postsynaptic repetitive depolarization alone in the absence of
      presynaptic inputs. The induction was dependent on voltage-dependent calcium
      channels instead of NMDA receptors (NMDARs), whereas the expression mechanism was
      shared with conventional NMDAR-dependent LTP. During the potentiation, the
      amplitude of spontaneous EPSCs was increased, suggesting a novel neuron-wide
      nature of this form of LTP. Furthermore, we also successfully induced LTP with
      trains of action potentials, which supported the possible existence of
      depolarizing pulse-induced LTP in vivo. Based on these findings, we suggest a
      model in which neuron-wide LTP works in concert with synapse-specific Hebbian
      plasticity to help information processing in memory formation.

PMID- 19741123
TI  - Astroglia in medullary dorsal horn (trigeminal spinal subnucleus caudalis) are
      involved in trigeminal neuropathic pain mechanisms.
AB  - The aim of this study was to investigate whether astroglia in the medullary
      dorsal horn (trigeminal spinal subnucleus caudalis; Vc) may be involved in
      orofacial neuropathic pain following trigeminal nerve injury. The effects of
      intrathecal administration of the astroglial aconitase inhibitor sodium
      fluoroacetate (FA) were tested on Vc astroglial hyperactivity [as revealed by
      glial fibrillary acid protein (GFAP) labeling], nocifensive behavior, Vc
      extracellular signal-regulated kinase phosphorylation (pERK), and Vc neuronal
      activity in inferior alveolar nerve-transected (IANX) rats. Compared with sham
      control rats, a significant increase occurred in GFAP-positive cells in
      ipsilateral Vc at postoperative day 7 in IANX rats, which was prevented following
      FA administration. FA significantly increased the reduced head withdrawal latency
      to high-intensity heat stimulation of the maxillary whisker pad skin in IANX
      rats, although it did not significantly affect the reduced escape threshold to
      low-intensity mechanical stimulation of the whisker skin in IANX rats. FA also
      significantly reduced the increased number of pERK-like immunoreactive cells in
      Vc and the enhanced Vc nociceptive neuronal responses following high-intensity
      skin stimulation that were documented in IANX rats, and glutamine administration
      restored the enhanced responses. These various findings provide the first
      documentation that astroglia is involved in the enhanced nociceptive responses of
      functionally identified Vc nociceptive neurons and in the associated orofacial
      hyperalgesia following trigeminal nerve injury.

PMID- 19741124
TI  - The tetraspanin KAI1/CD82 is expressed by late-lineage oligodendrocyte precursors
      and may function to restrict precursor migration and promote oligodendrocyte
      differentiation and myelination.
AB  - In the adult mammalian brain, oligodendrocyte progenitors can differentiate into
      mature oligodendrocytes during remyelination. Mechanisms that regulate migration
      and differentiation of progenitors are of great importance in understanding
      normal development and demyelinating/remyelinating conditions. In a microarray
      analysis comparing adult and neonatal O4-positive (+) cells, we found that the
      tetraspanin KAI1/CD82 is far more highly expressed in adult O4(+) cells than in
      neonatal O4(+) cells (Lin et al., 2009). CD82 is a metastasis suppressor, and its
      expression is often downregulated or lost in the advanced stages of metastatic
      cancer. We hypothesized that CD82 could be a factor that restricts migration and
      promotes differentiation of maturing oligodendrocytes. Western blot analysis of
      isolated adult O4(+) cells confirms the elevated levels of CD82, which continues
      to be expressed as these become O1(+) in vitro. In the adult rat white matter,
      CD82 is coexpressed with CC1 and olig2 but not with NG2 or GFAP. Immature cells
      of the neonatal forebrain subventricular zone (SVZ) infected in vivo with a
      retrovirus that constitutively expresses CD82 do not remain immature but
      differentiate into either CC1(+) and MBP(+) myelinating oligodendrocytes in the
      white matter or zebrinII(+) astrocytes in the cortex. Their migration from the
      SVZ is severely restricted. In contrast, downregulation of CD82 in SVZ cells in
      vivo, using retroviral-expressed short hairpin RNAs (shRNAs), prevents their
      differentiation into myelinating oligodendrocytes. shRNA-expressing cells
      remained PDGF receptor alpha positive, olig2(+), or NG2(+) or became CC1(+)
      nonmyelinating oligodendrocytes or GFAP(+) astrocytes. CD82 thus appears to be a
      critical molecule in the regulation of oligodendrocyte progenitor migration and
      myelination.

PMID- 19741125
TI  - Reward modulates attention independently of action value in posterior parietal
      cortex.
AB  - While numerous studies have explored the mechanisms of reward-based decisions
      (the choice of action based on expected gain), few have asked how reward
      influences attention (the selection of information relevant for a decision). Here
      we show that a powerful determinant of attentional priority is the association
      between a stimulus and an appetitive reward. A peripheral cue heralded the
      delivery of reward or no reward (these cues are termed herein RC+ and RC-,
      respectively); to experience the predicted outcome, monkeys made a saccade to a
      target that appeared unpredictably at the same or opposite location relative to
      the cue. Although the RC had no operant associations (did not specify the
      required saccade), they automatically biased attention, such that an RC+
      attracted attention and an RC- repelled attention from its location. Neurons in
      the lateral intraparietal area (LIP) encoded these attentional biases,
      maintaining sustained excitation at the location of an RC+ and inhibition at the
      location of an RC-. Contrary to the hypothesis that LIP encodes action value,
      neurons did not encode the expected reward of the saccade. Moreover, at odds with
      an adaptive decision process, the cue-evoked biases interfered with the required
      saccade, and these biases increased rather than abating with training. After
      prolonged training, valence selectivity appeared at shorter latencies and
      automatically transferred to a novel task context, suggesting that training
      produced visual plasticity. The results suggest that reward predictors gain
      automatic attentional priority regardless of their operant associations, and this
      valence-specific priority is encoded in LIP independently of the expected reward
      of an action.

PMID- 19741126
TI  - Nonlinear spectrotemporal interactions underlying selectivity for complex sounds
      in auditory cortex.
AB  - In the auditory cortex of awake animals, a substantial number of neurons do not
      respond to pure tones. These neurons have historically been classified as
      "unresponsive" and even been speculated as being nonauditory. We discovered,
      however, that many of these neurons in the primary auditory cortex (A1) of awake
      marmoset monkeys were in fact highly selective for complex sound features. We
      then investigated how such selectivity might arise from the tone-tuned inputs
      that these neurons likely receive. We found that these non-tone responsive
      neurons exhibited nonlinear combination-sensitive responses that require precise
      spectral and temporal combinations of two tone pips. The nonlinear
      spectrotemporal maps derived from these neurons were correlated with their
      selectivity for complex acoustic features. These non-tone responsive and
      nonlinear neurons were commonly encountered at superficial cortical depths in A1.
      Our findings demonstrate how temporally and spectrally specific nonlinear
      integration of putative tone-tuned inputs might underlie a diverse range of high
      selectivity of A1 neurons in awake animals. We propose that describing A1 neurons
      with complex response properties in terms of tone-tuned input channels can
      conceptually unify a wide variety of observed neural selectivity to complex
      sounds into a lower dimensional description.

PMID- 19741127
TI  - Short trains of theta frequency stimulation enhance CA1 pyramidal neuron
      excitability in the absence of synaptic potentiation.
AB  - Although plasticity at excitatory synapses is widely studied as a mechanism for
      memory formation, less is known about the properties and mechanisms underlying
      activity-dependent changes in excitability. Using extracellular and intracellular
      recordings in hippocampal slices, we find that short trains (2-3 s) of Schaffer
      collateral fiber stimulation delivered at 5 Hz induce a robust and persistent
      increase in the excitability of CA1 pyramidal cells in the absence of synaptic
      potentiation. This change in excitability is input specific, NMDA receptor
      dependent, and is not accompanied by lasting changes in either inhibitory
      synaptic transmission or somatic excitability. Although many of these properties
      are similar to those seen in synaptic long-term potentiation (LTP), the increase
      in CA1 pyramidal cell excitability was not blocked by inhibitors of several
      protein kinases required for the induction of LTP by theta frequency stimulation.
      Instead, 5 Hz stimulation-induced changes in neuronal excitability were blocked
      by inhibitors of the protein phosphatase calcineurin. Together, our results
      suggest that very brief bouts of theta frequency synaptic activity induce a
      selective, persistent, and dendritically localized increase in CA1 pyramidal cell
      excitability that might have an important role in both information storage and
      metaplasticity.

PMID- 19741128
TI  - Orexin A/hypocretin-1 selectively promotes motivation for positive reinforcers.
AB  - Orexin A/hypocretin-1 (oxA/hcrt-1) is known to be a modulator of dopamine
      dependent neuronal activity and behaviors. However, the role of this system in
      driving motivated behaviors remains poorly understood. Here, we show that
      orexin/hypocretin receptor-1 (ox/hcrt-1R) signaling is important for motivation
      for highly salient, positive reinforcement. Blockade of ox/hcrt-1R selectively
      reduced work to self-administer cocaine or high fat food pellets. Moreover,
      oxA/hcrt-1 strengthened presynaptic glutamatergic inputs to the ventral tegmental
      area (VTA) only in cocaine or high fat self-administering rats. Finally, oxA/hcrt
      1-mediated excitatory synaptic transmission onto VTA neurons was not potentiated
      following an arousing, aversive stimulus, suggesting that oxA/hcrt-1-mediated
      glutamatergic synaptic transmission was potentiated selectively with highly
      salient positive reinforcers. These experiments provide evidence for a selective
      role of oxA/hcrt-1 signaling in motivation for highly salient reinforcers and may
      represent a unique opportunity to design novel therapies that selectively reduce
      excessive drive to consume positive reinforcers of high salience.

PMID- 19741129
TI  - Statin's excitoprotection is mediated by sAPP and the subsequent attenuation of
      calpain-induced truncation events, likely via rho-ROCK signaling.
AB  - The widely used cholesterol-lowering drugs, statins, were reported to reduce the
      incidence of stroke and the progression of Alzheimer's disease. However, little
      is known on how statins exert these beneficial effects. In this study, we
      investigated the molecular mechanisms underlying the neuroprotective actions of
      statins in primary cultured cortical neurons. We found that chronic treatment of
      neurons with a low dosage of two CNS-permeable statins (lovastatin and
      simvastatin) selectively reduced NMDA-induced cell death but not the caspase
      mediated apoptosis. The protective effects of stains were inhibited by
      mevalonate, a PI3K inhibitor, and tyrphostin AG538, suggesting roles for
      cholesterol and insulin/IGF-1 signaling in the neurotoxic response. We further
      demonstrate that statins block calcium-dependent calpain activation, resulting in
      complete suppression of protein truncation events on multiple calpain substrates
      that are involved in neuronal death including CDK5 coactivator p35 cleavage to
      p25, GSK3 and beta-catenin. This is followed by reduced and increased nuclear
      translocation of p25 and beta-catenin, respectively. Under excitotoxic
      conditions, the activities of CDK5 and beta-catenin are exclusively regulated by
      calpain-mediated cleavage while apoptosis modulates beta-catenin mainly through
      phosphorylation. Strikingly, our data demonstrate that the calpain-blocking
      effect of statins is largely mediated by stimulation of alpha-secretase cleavage
      of APP, resulting in increased secretion of its soluble form, sAPP. Finally, our
      data suggest that statin-regulated sAPP secretion occurs via activation of the
      PI3K pathway and inhibition of ROCK signaling. Altogether, our study provides
      novel insights into statin-mediated neuronal excitoprotection through both
      cholesterol-dependent and -independent mechanisms and links them to calpain
      mediated neuronal death.

PMID- 19741130
TI  - Adenosine-evoked hyperpolarization of retinal ganglion cells is mediated by G
      protein-coupled inwardly rectifying K+ and small conductance Ca2+-activated K+
      channel activation.
AB  - Adenosine is a neuromodulator that activates presynaptic receptors to regulate
      synaptic transmission and postsynaptic receptors to hyperpolarize neurons. Here,
      we report that adenosine-induced hyperpolarization of retinal ganglion cells is
      produced by the activation of A(1) receptors, which initiates a signaling cascade
      that activates G-protein-coupled inwardly rectifying K(+) (GIRK) channels and
      small conductance Ca(2+)-activated K(+) (SK) channels. Rat retinal ganglion cells
      were stimulated by focal ejection of the adenosine receptor agonist 5'-N
      ethylcarboxamidoadenosine (NECA) while cell activity was monitored with whole
      cell patch recordings and Ca(2+) imaging. Focal ejections of NECA evoked outward
      currents in all cells tested and reduced light- and depolarization-induced
      spiking. The NECA-evoked current was abolished by the A(1) antagonist 1,3
      dipropyl-8-cyclopentylxanthine (DPCPX) but was unaffected by A(2a), A(2b), and
      A(3) antagonists, indicating that the response was mediated entirely by A(1)
      receptors. The GIRK channel blocker rTertiapin-Q diminished the NECA-evoked
      inhibitory current by 56 +/- 12%, whereas the SK channel blocker apamin decreased
      the NECA-induced current by 42 +/- 7%. The SK component of the NECA-evoked
      current coincided with an increase in intracellular Ca(2+) and was blocked by
      IP(3) receptor antagonists and depletion of internal Ca(2+) stores, suggesting
      that A(1) receptor activation leads to an increase in IP(3), which then elevates
      intracellular Ca(2+) and activates SK channels. This A(1)-mediated, prolonged SK
      channel activation has not been described previously. The coactivation of GIRK
      and SK channels represents a novel mechanism of adenosine-mediated
      neuromodulation that could contribute to the regulation of retinal ganglion cell
      activity.

PMID- 19741131
TI  - Fast kinetics, high-frequency oscillations, and subprimary firing range in adult
      mouse spinal motoneurons.
AB  - The fast contraction time of mouse motor units creates a unique situation in
      which motoneurons have to fire at low frequencies to produce small forces but
      also at very high frequency (much higher than in cat or rat motoneurons) to reach
      the fusion frequency of their motor units. To understand how this problem is
      solved, we performed intracellular recordings of adult mouse spinal motoneurons
      and investigated systematically their subthreshold properties and their discharge
      pattern. We show that mouse motoneurons have a much wider range of firing
      frequencies than cat and rat motoneurons because of three salient features.
      First, they have a short membrane time constant. This results in a higher cutoff
      frequency and a higher resonance frequency, which allow mouse motoneurons to
      integrate inputs at higher frequencies. Second, their afterhyperpolarization
      (AHP) is faster, allowing the motoneurons to discharge at a higher rate. Third,
      motoneurons display high-frequency (100-150 Hz) subthreshold oscillations during
      the interspike intervals. The fast membrane kinetics greatly favors the
      appearance of these oscillations, creating a "subprimary range" of firing. In
      this range, which has never been reported in cat and in rat spinal motoneurons,
      the oscillations follow the AHP and trigger spiking after a variable delay,
      allowing a discharge at low frequency but at the expense of an irregular rate.

PMID- 19741132
TI  - Parkin protects against LRRK2 G2019S mutant-induced dopaminergic
      neurodegeneration in Drosophila.
AB  - Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are currently
      recognized as the most common genetic cause of parkinsonism. Among the large
      number of LRRK2 mutations identified to date, the G2019S variant is the most
      common. In Asia, however, another LRRK2 variant, G2385R, appears to occur more
      frequently. To better understand the contribution of different LRRK2 variants
      toward disease pathogenesis, we generated transgenic Drosophila over-expressing
      various human LRRK2 alleles, including wild type, G2019S, Y1699C, and G2385R
      LRRK2. We found that transgenic flies harboring G2019S, Y1699C, or G2385R LRRK2
      variant, but not the wild-type protein, exhibit late-onset loss of dopaminergic
      (DA) neurons in selected clusters that is accompanied by locomotion deficits.
      Furthermore, LRRK2 mutant flies also display reduced lifespan and increased
      sensitivity to rotenone, a mitochondrial complex I inhibitor. Importantly,
      coexpression of human parkin in LRRK2 G2019S-expressing flies provides
      significant protection against DA neurodegeneration that occurs with age or in
      response to rotenone. Together, our results suggest a potential link between
      LRRK2, parkin, and mitochondria in the pathogenesis of LRRK2-related
      parkinsonism.

PMID- 19741133
TI  - Intact long-term potentiation but reduced connectivity between neocortical layer
      5 pyramidal neurons in a mouse model of Rett syndrome.
AB  - Mutations in MECP2 cause Rett syndrome and some related forms of mental
      retardation and autism. Mecp2-null mice exhibit symptoms reminiscent of Rett
      syndrome including deficits in learning. Previous reports demonstrated impaired
      long-term potentiation (LTP) in slices of symptomatic Mecp2-null mice, and
      decreased excitatory neurotransmission, but the causal relationship between these
      phenomena is unclear. Reduced plasticity could lead to altered transmission, or
      reduced excitatory transmission could alter the ability to induce LTP. To help
      distinguish these possibilities, we compared LTP induction and baseline synaptic
      transmission at synapses between layer 5 cortical pyramidal neurons in slices of
      wild-type and Mecp2-null mice. Paired recordings reveal that LTP induction
      mechanisms are intact in Mecp2-null connections, even after the onset of
      symptoms. However, fewer connections were found in Mecp2-null mice and individual
      connections were weaker. These data suggest that loss of MeCP2 function reduces
      excitatory synaptic connectivity and that this precedes deficits in plasticity.

PMID- 19741134
TI  - Taste-guided decisions differentially engage neuronal ensembles across gustatory
      cortices.
AB  - Much remains to be understood about the differential contributions from primary
      and secondary sensory cortices to sensory-guided decision making. To address this
      issue we simultaneously recorded activity from neuronal ensembles in primary
      [gustatory cortex GC)] and secondary gustatory [orbitofrontal cortex (OFC)]
      cortices while rats made a taste-guided decision between two response
      alternatives. We found that before animals commenced a response guided by a
      tastant cue, GC ensembles contained more information than OFC about the response
      alternative about to be selected. Thereafter, while the animal's response was
      underway, the response-selective information in ensembles from both regions
      increased, albeit to a greater degree in OFC. In GC, this increase depends on a
      representation of the taste cue guiding the animal's response. The increase in
      the OFC also depends on the taste cue guiding and other features of the response
      such as its spatiomotor properties and the behavioral context under which it is
      executed. Each of these latter features is encoded by different ensembles of OFC
      neurons that are recruited at specific times throughout the response selection
      process. These results indicate that during a taste-guided decision task both
      primary and secondary gustatory cortices dynamically encode different types of
      information.

PMID- 19741135
TI  - The synaptic connections between cortical areas V1 and V2 in macaque monkey.
AB  - The primary visual cortex (V1) and V2 together form approximately 24% of the
      total neocortex of the macaque monkey and have each other as their major
      partners. The major target of the V1 projection to V2 is layer 4, where it forms
      clusters of boutons, which form asymmetric (excitatory) synapses mainly with
      dendritic spines (75%). The remainder form synapses with dendritic shafts. The
      synapses found on spines were often more complex, perforated postsynaptic
      densities than those found on dendritic shafts. The reciprocal projection from V2
      to V1 targeted layers 1, 2/3, and 5 and was formed of axons of different
      morphologies. One axon type, originating from superficial layer pyramidal cells,
      had a morphology resembling those of local pyramidal cell collaterals. These
      axons arborized in layers 1, 2/3, and 5 of V1. Another type of axon, arborizing
      in layer 1, was slender (0.3 microm), unbranched, unmyelinated, and uniformly
      covered with boutons terminaux and formed asymmetric synapses mainly with slender
      spines. Yet a third type of axon also confined to layer 1, was thick (>1 microm),
      branched, heavily myelinated, and formed separate small clusters of large (
      approximately 1 microm) en passant multisynaptic boutons that formed asymmetric
      synapses mainly with large flat spines. These data show the existence of a
      reciprocal excitatory loop between V1 and V2 that is formed by different axonal
      types, each with preferred layers of termination.

PMID- 19741136
TI  - Brain-derived neurotrophic factor controls activity-dependent maturation of CA1
      synapses by downregulating tonic activation of presynaptic kainate receptors.
AB  - Immature hippocampal synapses express presynaptic kainate receptors (KARs), which
      tonically inhibit glutamate release. Presynaptic maturation involves activity
      dependent downregulation of the tonic KAR activity and consequent increase in
      release probability; however, the molecular mechanisms underlying this
      developmental process are unknown. Here, we have investigated whether brain
      derived neurotrophic factor (BDNF), a secreted protein implicated in
      developmental plasticity in several areas of the brain, controls presynaptic
      maturation by regulating KARs. Application of BDNF in neonate hippocampal slices
      resulted in increase in synaptic transmission that fully occluded the immature
      type KAR activity in area CA1. Conversely, genetic ablation of BDNF was
      associated with delayed synaptic maturation and persistent presynaptic KAR
      activity, suggesting a role for endogenous BDNF in the developmental regulation
      of KAR function. In addition, our data suggests a critical role for BDNF TrkB
      signaling in fast activity-dependent regulation of KARs. Selective acute
      inhibition of TrkB receptors using a chemical-genetic approach prevented rapid
      change in synapse dynamics and loss of tonic KAR activity that is typically seen
      in response to induction of LTP at immature synapses. Together, these data show
      that BDNF-TrkB-dependent maturation of glutamatergic synapses is tightly
      associated with a loss of endogenous KAR activity. The coordinated action of
      these two receptor mechanisms has immediate physiological relevance in
      controlling presynaptic efficacy and transmission dynamics at CA3-CA1 synapses at
      a stage of development when functional contact already exists but transmission is
      weak.

PMID- 19741137
TI  - Sustained axon-glial signaling induces Schwann cell hyperproliferation, Remak
      bundle myelination, and tumorigenesis.
AB  - Type III neuregulins exposed on axon surfaces control myelination of the
      peripheral nervous system. It has been shown, for example, that threshold levels
      of type III beta1a neuregulin dictate not only the myelination fate of axons but
      also myelin thickness. Here we show that another neuregulin isoform, type III
      beta3, plays a distinct role in myelination. Neuronal overexpression of this
      isoform in mice stimulates Schwann cell proliferation and dramatically enlarges
      peripheral nerves and ganglia-which come to resemble plexiform neurofibromas-but
      have no effect on myelin thickness. The nerves display other neurofibroma-like
      properties, such as abundant collagen fibrils and abundant dissociated Schwann
      cells that in some cases produce big tumors. Moreover, the organization of Remak
      bundles is dramatically altered; the small-caliber axons of each bundle are no
      longer segregated from one another within the cytoplasm of a nonmyelinating
      Schwann cell but instead are close packed and the whole bundle wrapped as a
      single unit, frequently by a compact myelin sheath. Because Schwann cell
      hyperproliferation and Remak bundle degeneration are early hallmarks of type I
      neurofibromatosis, we suggest that sustained activation of the neuregulin pathway
      in Remak bundles can contribute to neurofibroma development.

PMID- 19741138
TI  - Neurofilaments form a highly stable stationary cytoskeleton after reaching a
      critical level in axons.
AB  - The ultrastructural view of the axonal cytoskeleton as an extensively cross
      linked network of neurofilaments (NFs) and other cytoskeletal polymers contrasts
      with the dynamic view suggested by axonal transport studies on cytoskeletal
      elements. Here we reconcile these perspectives by showing that neurons form a
      large NF network along axons which is unequivocally stationary, metabolically
      stable, and maintained by NFs and nonfilamentous subunit assemblies undergoing
      slow transport by intermittent rapid movements and pauses. In mouse primary
      cortical neurons transfected with EGFP-NFL, formation of this stationary NF
      network requires a critical level of NFs, which explains its absence in NF-poor
      developing neurons studied previously. Most NFs at proximal axon regions were in
      a stationary structure coexisting with a smaller pool of moving EGFP-NFL
      assemblies that were mainly nonfilamentous. Distally along the same axon, EGFP
      labeled NFL was much less abundant, and we detected only short filaments moving
      bidirectionally by slow transport (rapid movements and pauses) as previously
      described. In living mice, >25% of radiolabeled newly synthesized NFs remained in
      optic axons after slowly transported NFs had exited. Retained NF remained fixed
      over several months in a nonuniform distribution and exhibited exceptionally slow
      turnover (t(1/2) >2.5 months), implying that, at steady state, >90% of NFs in
      mature optic axons comprise the stationary cytoskeleton and <10% are undergoing
      slow transport. These findings reconcile in vitro and in vivo axonal transport
      observations, showing that slowly transported NFs or subunit oligomers are
      precursors to a highly stable stationary cytoskeletal network that supports
      mature axons.

PMID- 19741139
TI  - Differential engagement of the ventromedial prefrontal cortex by goal-directed
      and habitual behavior toward food pictures in humans.
AB  - According to dual-system accounts, instrumental learning is supported by both a
      goal-directed and a habitual system. Although behavioral control by the goal
      directed system, through outcome-action associations, dominates with moderate
      training, stimulus-response associations are thought to form concurrently in the
      habit system. It is therefore challenging to isolate the neural substrate of the
      goal-directed system in neuroimaging research with healthy human volunteers.
      Recently, however, de Wit et al. (2007) developed an instrumental discrimination
      task that distinguishes between goal-directed and habit-based responding. In this
      task, cues are congruent, unrelated, or incongruent with subsequent outcomes.
      Whereas performance on congruent and control trials can be supported by both the
      goal-directed and habitual system, performance on the incongruent discrimination
      relies solely on the habit system. In the present study, we used this task with
      healthy participants undergoing functional magnetic resonance imaging to
      demonstrate that engagement of the goal-directed system during learning is
      reflected in increased activity in the ventromedial prefrontal cortex. Moreover,
      using a subsequent outcome devaluation manipulation, we show that this area is
      involved in guiding decision making when goal values change, even in the absence
      of external cues to guide performance. We can therefore exclude a purely
      Pavlovian account of ventromedial prefrontal function and unequivocally
      demonstrate its involvement in the acquisition as well as deployment of goal
      directed knowledge.

PMID- 19741140
TI  - Spontaneous glial calcium waves in the retina develop over early adulthood.
AB  - Intercellular glial Ca(2+) waves constitute a signaling pathway between glial
      cells. Artificial stimuli have previously been used to evoke these waves, and
      their physiological significance has been questioned. We report here that Ca(2+)
      waves occur spontaneously in rat retinal glial cells, both in the isolated retina
      and in vivo. These spontaneous waves are propagated by ATP release. In the
      isolated retina, suramin (P2 receptor antagonist) reduces the frequency of
      spontaneous wave generation by 53%, and apyrase (ATP-hydrolyzing enzyme) reduces
      frequency by 95-100%. Luciferin-luciferase chemiluminescence reveals waves of ATP
      matching the spontaneous Ca(2+) waves, indicating that ATP release occurs as
      spontaneous Ca(2+) waves are generated. Wave generation also depends on age.
      Spontaneous wave frequency rises from 0.27 to 1.0 per minute per mm(2), as rats
      age from 20 to 120 d. The sensitivity of glia to ATP does not increase with age,
      but the ATP released by evoked waves is 31% greater in 120-d-old than in 20-d-old
      rats, suggesting that increased ATP release in older animals could account for
      the higher frequency of wave generation. Simultaneous imaging of glial Ca(2+) and
      arterioles in the isolated retina demonstrates that spontaneous waves alter
      vessel diameter, implying that spontaneous waves may have a significant impact on
      retinal physiology. Spontaneous intercellular glial Ca(2+) waves also occur in
      the retina in vivo, with frequency, speed, and diameter similar to the isolated
      retina. Increased spontaneous wave occurrence with age suggests that wave
      generation may be related to retinal pathology.

PMID- 19741142
TI  - Role of glial cell line-derived neurotrophic factor (GDNF)-neural cell adhesion
      molecule (NCAM) interactions in induction of neurite outgrowth and identification
      of a binding site for NCAM in the heel region of GDNF.
AB  - The formation of appropriate neuronal circuits is an essential part of nervous
      system development and relies heavily on the outgrowth of axons and dendrites and
      their guidance to their respective targets. This process is governed by a large
      array of molecules, including glial cell line-derived neurotrophic factor (GDNF)
      and the neural cell adhesion molecule (NCAM), the interaction of which induce
      neurite outgrowth. In the present study the requirements for NCAM-mediated GDNF
      induced neurite outgrowth were investigated in cultures of hippocampal neurons,
      which do not express Ret. We demonstrate that NCAM-mediated GDNF-induced
      signaling leading to neurite outgrowth is more complex than previously reported.
      It not only involves NCAM-140 and the Src family kinase Fyn but also uses NCAM
      180 and the fibroblast growth factor receptor. We find that induction of neurite
      outgrowth by GDNF via NCAM or by trans-homophilic NCAM interactions are not
      mutually exclusive. However, whereas NCAM-induced neurite outgrowth primarily is
      mediated by NCAM-180, we demonstrate that GDNF-induced neurite outgrowth involves
      both NCAM-140 and NCAM-180. We also find that GDNF-induced neurite outgrowth via
      NCAM differs from NCAM-induced neurite outgrowth by being independent of NCAM
      polysialylation. Additionally, we investigated the structural basis for GDNF-NCAM
      interactions and find that NCAM Ig3 is necessary for GDNF binding. Furthermore,
      we identify within the heel region of GDNF a binding site for NCAM and
      demonstrate that a peptide encompassing this sequence mimics the effects of GDNF
      with regard to NCAM binding, activation of intracellular signaling, and induction
      of neurite outgrowth.

PMID- 19741141
TI  - Aberrant frontoparietal function during recognition memory in schizophrenia: a
      multimodal neuroimaging investigation.
AB  - Prefrontal-parietal networks are essential to many cognitive processes, including
      the ability to differentiate new from previously presented items. As patients
      with schizophrenia exhibit structural abnormalities in these areas along with
      well documented decrements in recognition memory, we hypothesized that these
      patients would demonstrate memory-related abnormalities in prefrontal and
      parietal physiology as measured by both functional magnetic resonance imaging and
      magnetoencephalography (MEG). Medicated outpatients with schizophrenia (n = 18)
      and age-matched healthy control subjects (n = 18) performed an old-new
      recognition memory task while physiological data were obtained. Whereas controls
      exhibited strong, bilateral activation of prefrontal and posterior parietal
      regions during successful identification of old versus new items, patients
      exhibited greatly attenuated activation of the right prefrontal and parietal
      cortices. However, within the patient group, there was strong correlation between
      memory performance and activation of these right-sided regions as well as a tight
      correlation between old-new effect-related activations in frontal and parietal
      regions, a pattern not seen in control subjects. Using MEG, control subjects-but
      not patients-exhibited a sequential pattern of old > new activity in the left
      posterior parietal cortex and then right prefrontal cortex; however, patients
      uniquely exhibited old > new activity in right temporal cortex. Collectively,
      these findings point to markedly different distributions of regional
      specialization necessary to complete the old-new item recognition task in
      patients versus controls. Inefficient utilization of prefrontal-parietal
      networks, with compensatory activation in temporal regions, may thus contribute
      to deficient old-new item recognition in schizophrenia.

PMID- 19741143
TI  - Overlapping function of Lmx1a and Lmx1b in anterior hindbrain roof plate
      formation and cerebellar growth.
AB  - The roof plate is an organizing center in the dorsal CNS that controls
      specification and differentiation of adjacent neurons through secretion of the
      BMP and WNT signaling molecules. Lmx1a, a member of the LIM-homeodomain (LIM-HD)
      transcription factor family, is expressed in the roof plate and its progenitors
      at all axial levels of the CNS and is necessary and sufficient for roof plate
      formation in the spinal cord. In the anterior CNS, however, a residual roof plate
      develops in the absence of Lmx1a. Lmx1b, another member of the LIM-HD
      transcription factor family which is highly related to Lmx1a, is expressed in the
      roof plate in the anterior CNS. Although Lmx1b-null mice do not show a
      substantial deficiency in hindbrain roof plate formation, Lmx1a/Lmx1b compound
      null mutants fail to generate hindbrain roof plate. This observation indicates
      that both genes act in concert to direct normal hindbrain roof plate formation.
      Since the requirement of Lmx1b function for normal isthmic organizer at the mid
      hindbrain boundary complicates analysis of a distinct dorsal patterning role of
      this gene, we also used a conditional knock-out strategy to specifically delete
      dorsal midline Lmx1b expression. Phenotypic analysis of single and compound
      conditional mutants confirmed overlapping roles for Lmx1 genes in regulating
      hindbrain roof plate formation and growth and also revealed roles in regulating
      adjacent cerebellar morphogenesis. Our data provides the first evidence of
      overlapping function of the Lmx1 genes during embryonic CNS development.

PMID- 19741144
TI  - Caspase-9 activation revealed by semaphorin 7A cleavage is independent of
      apoptosis in the aged olfactory bulb.
AB  - Caspases are essential in multicellular organisms for inducing cell death during
      normal development and in the immune system. However, caspases can also trigger
      the degenerative process under certain conditions such as pathophysiological
      conditions and aging. Here, we identified Semaphorin 7A (Sema7A) as a novel
      substrate for caspase-9 that can be used to monitor caspase-9 activity in mice,
      and found nonapoptotic caspase-9 activation in the aged olfactory bulb (OB).
      Immunostaining of the OB for the caspase-9-cleaved form of Sema7A revealed
      abundant caspase-9-activated cells in 2-year-old (aged) but not in 2-month-old
      (young) mice. In fact, various regions of the aged brain, including the OB,
      exhibited an increased level of caspase-9 activity. However, the number of dying
      cells in the aged OB was, intriguingly, much lower (<20%) than in the OB of young
      mice. Furthermore, we found that the lower number dying cells in the aged OB was
      accompanied by a decreased expression of procaspase-3. These results suggest a
      survival strategy for aged OB neurons, which can no longer regenerate, in which
      the central apoptotic machinery downstream of caspase-9 is inactivated.

PMID- 19741145
TI  - Abeta immunotherapy: intracerebral sequestration of Abeta by an anti-Abeta
      monoclonal antibody 266 with high affinity to soluble Abeta.
AB  - Amyloid beta (Abeta) immunotherapy is emerging as a promising disease-modifying
      therapy for Alzheimer's disease, although the precise mechanisms whereby anti
      Abeta antibodies act against amyloid deposition and cognitive deficits remain
      elusive. To test the "peripheral sink" theory, which postulates that the effects
      of anti-Abeta antibodies in the systemic circulation are to promote the Abeta
      efflux from brain to blood, we studied the clearance of (125)I-Abeta(1-40)
      microinjected into mouse brains after intraperitoneal administration of an anti
      Abeta monoclonal antibody 266. (125)I-Abeta(1-40) was rapidly eliminated from
      brains with a half-life of approximately 30 min in control mice, whereas 266
      significantly retarded the elimination of Abeta, presumably due to formation of
      Abeta-antibody complex in brains. Administration of 266 to APP transgenic mice
      increased the levels of monomer Abeta species in an antibody-bound form, without
      affecting that of total Abeta. We propose a novel mechanism of Abeta
      immunotherapy by the class of anti-Abeta antibodies that preferentially bind
      soluble Abeta, i.e., intracerebral, rather than peripheral, sequestration of
      soluble, monomer form of Abeta, thereby preventing the accumulation of multimeric
      toxic Abeta species in brains.

PMID- 19741146
TI  - A genome-wide screen for spatially restricted expression patterns identifies
      transcription factors that regulate glial development.
AB  - Forward genetic screens in genetically accessible invertebrate organisms such as
      Drosophila melanogaster have shed light on transcription factors that specify
      formation of neurons in the vertebrate CNS. However, invertebrate models have, to
      date, been uninformative with respect to genes that specify formation of the
      vertebrate glial lineages. All recent insights into specification of vertebrate
      glia have come via monitoring the spatial and temporal expression patterns of
      individual transcription factors during development. In studies described here,
      we have taken this approach to the genome scale with an in silico screen of the
      Mahoney pictorial atlas of transcription factor expression in the developing CNS.
      From the population of 1445 known or probable transcription factors encoded in
      the mouse genome, we identify 12 novel transcription factors that are expressed
      in glial lineage progenitor cells. Entry-level screens for biological function
      establish one of these transcription factors, Klf15, as sufficient for genesis of
      precocious GFAP-positive astrocytes in spinal cord explants. Another
      transcription factor, Tcf4, plays an important role in maturation of
      oligodendrocyte progenitors.

PMID- 19741147
TI  - The spatiotemporal frequency tuning of LGN receptive field facilitates neural
      discrimination of natural stimuli.
AB  - The efficient coding hypothesis suggests that the early visual system is
      optimized to represent stimuli in the natural environment. While it is believed
      that LGN processing removes the redundant information of natural scenes, it is
      not clear whether the early visual processing can selectively amplify important
      signals in natural stimuli to facilitate discrimination. In this study, we
      examined the functional role of LGN spatiotemporal frequency tuning in the
      processing of natural scenes. First, we characterized the relationship between
      spatial and temporal frequency tuning for LGN receptive fields. We found that LGN
      neurons exhibit inseparable spatiotemporal frequency tuning in a manner
      consistent with the feature of optimal filters that can maximize information
      transmission of natural scenes. Second, we analyzed the spatiotemporal power
      spectrum of natural scenes and found that some frequencies exhibit larger
      variation in power across different scenes. Interestingly, the preferred
      frequency of ensemble LGN neurons matches the range of frequencies in which
      natural power spectrum varies most. Comparison of neural discrimination for
      natural stimuli and for artificial stimuli with similar mean power spectra but
      different variation structure showed that the match between LGN tuning and
      natural spectra variation enhances neural discrimination for natural stimuli. Our
      results indicate that, in addition to removing redundancy, the spatiotemporal
      frequency characteristics of LGN neurons can facilitate neural discrimination of
      natural stimuli.

PMID- 19741148
TI  - Effectiveness of donepezil, rivastigmine, and (+/-)huperzine A in counteracting
      the acute toxicity of organophosphorus nerve agents: comparison with galantamine.
AB  - Galantamine, a centrally acting cholinesterase (ChE) inhibitor and a nicotinic
      allosteric potentiating ligand used to treat Alzheimer's disease, is an effective
      and safe antidote against poisoning with nerve agents, including soman. Here, the
      effectiveness of galantamine was compared with that of the centrally active ChE
      inhibitors donepezil, rivastigmine, and (+/-)huperzine A as a pre- and/or post
      treatment to counteract the acute toxicity of soman. In the first set of
      experiments, male prepubertal guinea pigs were treated intramuscularly with one
      of the test drugs and 30 min later challenged with 1.5 x LD(50) soman (42
      microg/kg s.c.). All animals that were pretreated with galantamine (6-8 mg/kg), 3
      mg/kg donepezil, 6 mg/kg rivastigmine, or 0.3 mg/kg (+/-)huperzine A survived the
      soman challenge, provided that they were also post-treated with atropine (10
      mg/kg i.m.). However, only galantamine was well tolerated. In subsequent
      experiments, the effectiveness of specific treatment regimens using 8 mg/kg
      galantamine, 3 mg/kg donepezil, 6 mg/kg rivastigmine, or 0.3 mg/kg (+/-)huperzine
      A was compared in guinea pigs challenged with soman. In the absence of atropine,
      only galantamine worked as an effective and safe pretreatment in animals
      challenged with 1.0 x LD(50) soman. Galantamine was also the only drug to afford
      significant protection when given to guinea pigs after 1.0 x LD(50) soman.
      Finally, all test drugs except galantamine reduced the survival of the animals
      when administered 1 or 3 h after the challenge with 0.6 or 0.7 x LD(50) soman.
      Thus, galantamine emerges as a superior antidotal therapy against the toxicity of
      soman.

PMID- 19741149
TI  - Inhibition of thromboxane A2-induced arrhythmias and intracellular calcium
      changes in cardiac myocytes by blockade of the inositol trisphosphate pathway.
AB  - We have recently reported that left atrial injections of the thromboxane A(2)
      (TXA(2)) mimetic, (5Z)-7-[(1R,4S,5S,6R)-6-[(1E,3S)-3-hydroxy-1-octenyl]-2 
      oxabicyclo[2.2.1]hept-5-yl]-5-heptenoic acid (U46619), induced ventricular
      arrhythmias in the anesthetized rabbit. Data from this study led us to
      hypothesize that TXA(2) may be inducing direct actions on the myocardium to
      induce these arrhythmias. The aim of this study was to further elucidate the
      mechanism responsible for these arrhythmias. We report that TXA(2)R is expressed
      at both the gene and protein levels in atrial and ventricular samples of adult
      rabbits. In addition, TXA(2)R mRNA was identified in single, isolated ventricular
      cardiac myocytes. Furthermore, treatment of isolated cardiac myocytes with U46619
      increased intracellular calcium in a dose-dependent manner and these increases
      were blocked by the specific TXA(2)R antagonist, 7-(3-((2
      ((phenylamino)carbonyl)hydrazino)methyl)-7-oxabicyclo(2.2.1)hept-2-yl)-5
      heptenoic acid (SQ29548). Pretreatment of myocytes with an inhibitor of inositol
      trisphosphate (IP(3)) formation, gentamicin, or with an inhibitor of IP(3)
      receptors, 2-aminoethoxydiphenylborate (2-APB), blocked the increase in
      intracellular calcium. In vivo pretreatment of anesthetized rabbits with either
      gentamicin or 2-APB subsequently inhibited the formation of ventricular
      arrhythmias elicited by U46619. These data support the hypothesis that TXA(2) can
      induce arrhythmias via a direct action on cardiac myocytes. Furthermore, these
      arrhythmogenic actions were blocked by inhibitors of the IP(3) pathway. In
      summary, this study provides novel evidence for direct TXA(2)-induced cardiac
      arrhythmias and provides a rationale for IP(3) as a potential target for the
      treatment of TXA(2)-mediated arrhythmias.

PMID- 19741150
TI  - Neuroprotective profile of novel SRC kinase inhibitors in rodent models of
      cerebral ischemia.
AB  - Src kinase signaling has been implicated in multiple mechanisms of ischemic
      injury, including vascular endothelial growth factor (VEGF)-mediated vascular
      permeability that leads to vasogenic edema, a major clinical complication in
      stroke and brain trauma. Here we report the effects of two novel Src kinase
      inhibitors, 4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(4-methyl-1
      piperazinyl)propoxy]-3-quinolinecarbonitrile (SKI-606) and 4-[(2,4-dichloro-5
      methoxyphenyl)amino]-6-methoxy-7-[4-(4-methypiperazin-1-yl)but-1-ynyl]-3
      quinolinecarbonitrile (SKS-927), on ischemia-induced brain infarction and short-
      and long-term neurological deficits. Two well established transient [transient
      middle cerebral artery occlusion (tMCAO)] and permanent [permanent middle
      cerebral artery occlusion (pMCAO)] focal ischemia models in the rat were used
      with drug treatments initiated up to 6 h after onset of stroke to mimic the
      clinical scenario. Brain penetration of Src inhibitors, their effect on blood
      brain barrier integrity and VEGF signaling in human endothelial cells were also
      evaluated. Our results demonstrate that both agents potently block VEGF-mediated
      signaling in human endothelial cells, penetrate rat brain upon systemic
      administration, and inhibit postischemic Src activation and vascular leakage.
      Treatment with SKI-606 or SKS-927 (at the doses of 3-30 mg/kg i.v.) resulted in a
      dose-dependent reduction in infarct volume and robust protection from
      neurological impairments even when the therapy was initiated up to 4- to 6-h
      after tMCAO. Src blockade after pMCAO resulted in accelerated improvement in
      recovery from motor, sensory, and reflex deficits during a long-term (3 weeks)
      testing period poststroke. These data demonstrate that the novel Src kinase
      inhibitors provide effective treatment against ischemic conditions within a
      clinically relevant therapeutic window and may constitute a viable therapy for
      acute stroke.

PMID- 19741151
TI  - Cellular inhibition of checkpoint kinase 2 (Chk2) and potentiation of
      camptothecins and radiation by the novel Chk2 inhibitor PV1019 [7-nitro-1H-indole
      2-carboxylic acid {4-[1-(guanidinohydrazone)-ethyl]-phenyl}-amide].
AB  - Chk2 is a checkpoint kinase involved in the ataxia telangiectasia mutated
      pathway, which is activated by genomic instability and DNA damage, leading to
      either cell death (apoptosis) or cell cycle arrest. Chk2 provides an unexplored
      therapeutic target against cancer cells. We recently reported 4,4'
      diacetyldiphenylurea-bis(guanylhydrazone) (NSC 109555) as a novel chemotype Chk2
      inhibitor. We have now synthesized a derivative of NSC 109555, PV1019 (NSC
      744039) [7-nitro-1H-indole-2-carboxylic acid {4-[1-(guanidinohydrazone)-ethyl]
      phenyl}-amide], which is a selective submicromolar inhibitor of Chk2 in vitro.
      The cocrystal structure of PV1019 bound in the ATP binding pocket of Chk2
      confirmed enzymatic/biochemical observations that PV1019 acts as a competitive
      inhibitor of Chk2 with respect to ATP. PV1019 was found to inhibit Chk2 in cells.
      It inhibits Chk2 autophosphorylation (which represents the cellular kinase
      activation of Chk2), Cdc25C phosphorylation, and HDMX degradation in response to
      DNA damage. PV1019 also protects normal mouse thymocytes against ionizing
      radiation-induced apoptosis, and it shows synergistic antiproliferative activity
      with topotecan, camptothecin, and radiation in human tumor cell lines. We also
      show that PV1019 and Chk2 small interfering RNAs can exert antiproliferative
      activity themselves in the cancer cells with high Chk2 expression in the NCI-60
      screen. These data indicate that PV1019 is a potent and selective inhibitor of
      Chk2 with chemotherapeutic and radiosensitization potential.

PMID- 19741152
TI  - Oral administration of 1,4-aryl-2-mercaptoimidazole inhibits T-cell proliferation
      and reduces clinical severity in the murine experimental autoimmune
      encephalomyelitis model.
AB  - T cells play a pivotal role in the initiation and progression of multiple
      sclerosis. We have found that 1,4-aryl-2-mercaptoimidazole (KRM-III) inhibited T
      cell antigen receptor- and phorbol myristate acetate/ionomycin-induced activation
      of nuclear factor of activated T cells (NFAT) and T-cell proliferation with an
      IC(50) of 5 microM. The KRM-III-mediated inhibitory effect was specific for NFAT
      activation but not for nuclear factor kappaB. Oral administration of 90 mg/kg KRM
      III resulted in complete abrogation of anti-CD3 antibody-induced T-cell
      activation and a 45.8% reduction in footpad swelling in bovine serum albumin
      induced delayed-type hypersensitivity. In the murine experimental autoimmune
      encephalomyelitis (EAE) model, oral administration of KRM-III significantly
      attenuated the severity of disease when given before or after disease onset.
      Draining lymph node cells from KRM-III-treated mice showed markedly reduced
      proliferation in response to myelin oligodendrocyte glycoprotein peptide.
      Histological analysis indicated that KRM-III reduced the infiltration of
      inflammatory cells to the white matter of spinal lumbar cords. These results
      demonstrate that KRM-III efficiently inhibits T-cell activation and inflammatory
      responses and lessens EAE clinical signs, which suggest KRM-III as a potential
      lead compound for the treatment of T-cell-driven autoimmune diseases.

PMID- 19741153
TI  - The biosocial correlates of neuropsychological deficits: results from the
      national longitudinal study of adolescent health.
AB  - A body of empirical research has revealed that neuropsychological functioning is
      one of the most consistent predictors of antisocial behavior. It is somewhat
      surprising however that criminological research has been slow to examine the
      different factors that are implicated in the development of neuropsychological
      deficits. This study addresses this gap in the literature by examining the
      effects that a number of social and biological variables have on
      neuropsychological functioning. Analysis of the National Longitudinal Study of
      Adolescent Health (Add Health) indicates that postnatal exposure to cigarette
      smoke, duration of breastfeeding, maternal involvement, and household income
      predicts variation in adolescent and adulthood levels of neuropsychological
      functioning. Implications of the findings are noted and discussed.

PMID- 19741154
TI  - Ficolin-1 is present in a highly mobilizable subset of human neutrophil granules
      and associates with the cell surface after stimulation with fMLP.
AB  - Ficolins are soluble molecules that bind carbohydrate present on the surface of
      microorganisms and function as recognition molecules in the lectin complement
      pathway. Three ficolins have been identified in humans: ficolin-1, ficolin-2, and
      ficolin-3. Ficolin-1 is synthesized in monocytes and type II alveolar epithelial
      cells. Ficolin-1 has been shown to be present in secretory granules of human
      neutrophils, but it is not known which subset of the neutrophils' secretory
      granules harbors ficolin-1. To determine the exact subcellular localization of
      ficolin-1 in neutrophils, recombinant ficolin-1 was expressed in Chinese hamster
      ovary cells and used for generation of polyclonal antibodies. This allowed
      detection of ficolin-1 in subcellular fractions of human neutrophils by ELISA, by
      Western blotting, and by immunohistochemistry. Real-time PCR examination of
      normal human bone marrow showed FCN1 gene expression largely in myelocytes,
      metamyelocytes, and band cells with a profile quite similar to that of
      gelatinase. In accordance with this, biosynthesis studies of neutrophils
      precursor cells showed that ficolin-1 was primarily synthesized in myelocytes,
      metamyelocytes, and band cells. Immunohistochemistry and subcellular
      fractionation demonstrated that ficolin-1 is primarily localized in gelatinase
      granules but also in highly exocytosable gelatinase-poor granules, not described
      previously. Ficolin-1 is released from neutrophil granules by stimulation with
      fMLP or PMA, and the majority becomes associated with the surface membrane of the
      cells and can be detected by flow cytometry. Our studies show that neutrophils
      are a major source of ficolin-1, which can be readily exocytosed by stimulation.

PMID- 19741155
TI  - CD4(+)CD25(+) regulatory T cells attenuate Hypersensitivity Pneumonitis by
      suppressing IFN-gamma production by CD4(+) and CD8(+) T cells.
AB  - HP results from the repeated inhalation of environmental antigens; however, the
      roles of CD4(+)CD25(+) T(reg) cells in HP are unknown. Therefore, we investigated
      the functions of CD4(+)CD25(+) T(reg) cells in SR-induced murine HP. More severe
      HP was observed in CD4(+)CD25(+) T(reg) cell-depleted mice than in control mice
      in terms of histological alterations, inflammatory cell numbers in BALF, and the
      serum level of SR-specific IgG, which were restored by the adoptive transfer of
      CD4(+)CD25(+) T(reg) cells. The CD4(+)CD25(+) T(reg) cell-depleted mice also
      showed elevated levels of IFN-gamma, TGF-beta, and reduced IL-4 production in the
      lungs. Moreover, IL-10 production of CD4(+)CD25(+) T(reg) cells and direct
      contact between CD4(+)CD25(+) T(reg) cells and CD4(+) or CD8(+) T cells in BALF
      resulted in reduced IFN-gamma production. Taken together, CD4(+)CD25(+) T(reg)
      cells play a protective role in SR-induced HP by suppressing IFN-gamma production
      by T cells.

PMID- 19741156
TI  - Development and function of IL-10 IFN-gamma-secreting CD4(+) T cells.
AB  - IL-10 IFN-gamma-secreting CD4(+) T cells were first found in the early 1990s.
      They are suppressive T cells able to inhibit cytotoxic T lymphocytes. These cells
      (Foxp3-T bet(+)) have a similar function but are distinct from conventional
      Tregs. The production of IL-10 in these cells requires IL-27 and TGF-beta and was
      regulated by several signal pathways including Notch, STAT, and NF-kappaB. The
      crosstalk among these pathways is critical for the generation and function of
      these cells. IL-10 IFN-gamma-secreting CD4(+) T cells are activated in chronic
      infection and are responsible for prolonged infection. Thus, their modulation has
      therapeutic implications for the treatment of infectious diseases. However, it is
      complicated, and fine-tuning of IFN-gamma and IL-10 secretion by these cells is
      needed for disease management, as inhibition of these cells will also lead to
      overimmune responses. On the other hand, increasing their numbers in autoimmune
      diseases may have beneficial effects.

PMID- 19741157
TI  - Tumor-associated macrophages (TAM) as major players of the cancer-related
      inflammation.
AB  - The microenvironment of solid tumors is characterized by a reactive stroma with
      an abundance of inflammatory mediators and leukocytes, dysregulated vessels and
      proteolytic enzymes. TAM, major players in the connection between inflammation
      and cancer, summarize a number of functions (e.g., promotion of tumor cell
      proliferation and angiogenesis, incessant matrix turnover, repression of adaptive
      immunity), which ultimately have an important impact on disease progression.
      Thus, together with other myeloid-related cells present at the tumor site (Tie2
      macrophages and MDSCs), TAM represent an attractive target of novel biological
      therapies of tumors.

PMID- 19741158
TI  - Characterization of Cdk9 T-loop phosphorylation in resting and activated CD4(+) T
      lymphocytes.
AB  - The cellular kinase complex P-TEFb is composed of Cdk9 and cyclin T, and it is
      required for expression of most protein-coding genes by RNAP II. Cdk9 has been
      shown recently to be activated in cis by autophosphorylation of Thr186 in its T
      loop. Using a phosphospecific Cdk9 antibody, we examined the level of Cdk9 T-loop
      phosphorylation in resting and activated CD4(+) T lymphocytes. Cdk9 T-loop
      phosphorylation was found to be low-to-undetectable in resting CD4(+) T
      lymphocytes, and upon activation by distinct stimuli, there is a rapid (<1 h)
      increase in pCdk9 that does not require protein synthesis. The low level of Cdk9
      T-loop phosphorylation was not to be a result of the absence of an associated
      regulatory cyclin partner. These observations suggest that autophosphorylation of
      the Cdk9 T-loop is repressed in resting CD4(+) T lymphocytes. The low level of T
      loop phosphorylation in resting cells is also reflected in a low level of
      phosphorylation of Ser2 in the carboxyl terminal domain of RNAP II, suggesting
      that lack of Cdk9 T-loop autophosphorylation may limit RNAP II elongation in
      quiescent CD4(+) T lymphocytes.

PMID- 19741159
TI  - IgE signaling suppresses FcepsilonRIbeta expression.
AB  - Activation of the high-affinity receptor for IgE, FcepsilonRI, is known to elicit
      its rapid down-regulation through internalization and degradation. In keeping
      with this, expression of all three FcepsilonRI subunits is decreased at the
      protein level after cross-linkage of IgE with antigen. However, we find that the
      FcepsilonRI beta-subunit is also selectively suppressed at the mRNA level,
      through a pathway primarily involving Fyn, Syk, PI3K, and NF-kappaB. IgG or
      calcium ionophore, stimuli known to mimic portions of the IgE signaling cascade,
      similarly suppressed beta-subunit expression. LPS, a NF-kappaB-activating TLR
      ligand, did not alter beta-subunit expression. As IgE increases FcepsilonRI
      expression, we examined the coordinated regulation of FcepsilonRI subunits during
      culture with IgE, followed by cross-linkage with antigen. IgE increased the
      expression of all three FcepsilonRI subunits and strikingly induced expression of
      the antagonistic beta(T). The ratio of beta:beta(T) protein expression decreased
      significantly during culture with IgE and was reset to starting levels by antigen
      cross-linkage. These changes in protein levels were matched by similar
      fluctuations in beta and beta(T) mRNAs. FcepsilonRIbeta is a key regulator of
      IgER expression and function, a gene in which polymorphisms correlate with
      allergic disease prevalence. The ability of IgE and FcepsilonRI signaling to
      coordinate expression of the beta and beta(T) subunits may comprise a homeostatic
      feedback loop-one that could promote chronic inflammation and allergic disease if
      dysregulated.

PMID- 19741160
TI  - Effects of PARP-1 deficiency on airway inflammatory cell recruitment in response
      to LPS or TNF: differential effects on CXCR2 ligands and Duffy Antigen Receptor
      for Chemokines.
AB  - We reported that PARP-1 exhibits differential roles in expression of inflammatory
      factors. Here, we show that PARP-1 deletion was associated with a significant
      reduction in inflammatory cell recruitment to mouse airways upon intratracheal
      administration of LPS. However, PARP-1 deletion exerted little effect in response
      to TNF exposure. LPS induced massive neutrophilia and moderate recruitment of
      macrophages, and TNF induced recruitment of primarily macrophages with smaller
      numbers of neutrophils in the lungs. Following either exposure, macrophage
      recruitment was blocked severely in PARP-1(-/-) mice, and this was associated
      with a marked reduction in MCP-1 and MIP-1alpha. This association was
      corroborated partly by macrophage recruitment in response to intratracheal
      administration of MCP-1 in PARP-1(-/-) mice. Surprisingly, although neutrophil
      recruitment was reduced significantly in LPS-treated PARP-1(-/-) mice, neutrophil
      numbers increased in TNF-treated mice, suggesting that PARP-1 deletion may
      promote a macrophagic-to-neutrophilic shift in the inflammatory response upon TNF
      exposure. Neutrophil-specific chemokines mKC and MIP-2 were reduced significantly
      in lungs of LPS-treated but only partially reduced in TNF-treated PARP-1(-/-)
      mice. Furthermore, the MIP-2 antagonist abrogated the shift to a neutrophilic
      response in TNF-exposed PARP-1(-/-) mice. Although CXCR2 expression increased in
      response to either stimulus in PARP-1(+/+) mice, the DARC increased only in lungs
      of TNF-treated PARP-1(+/+) mice; both receptors were reduced to basal levels in
      treated PARP-1(-/-) mice. Our results show that the balance of pro-neutrophilic
      or pro-macrophagic stimulatory factors and the differential influence of PARP-1
      on these factors are critical determinants for the nature of the airway
      inflammatory response.

PMID- 19741161
TI  - The sympathetic nervous system modulates CD4(+)FoxP3(+) regulatory T cells via a
      TGF-beta-dependent mechanism.
AB  - CD4(+)FoxP3(+) Tregs are essential mediators of the peripheral immune response to
      self-antigens. Accordingly, the homeostatic regulation of Treg activity and
      number would impact on the immune response to both self- and non-self antigens.
      Because the sympathetic nervous system (SNS) interacts chemically and physically
      with the central and peripheral immune system and exerts a direct influence on
      antigen-presenting cells and effector lymphocytes, we have investigated the
      effect of chemical ablation of the SNS on the number and function of peripheral
      Treg. Removal of murine peripheral sympathetic innervation by 6-hydroxydopamine
      induced an increase in splenic and lymph node CD4(+)FoxP3(+) Tregs by a TGF-beta
      dependent mechanism. Further, this increase in Tregs coincides with an inhibition
      of the induction of experimental autoimmune encephalomyelitis. Our results
      demonstrate that the SNS is an important contributor to the maintenance of
      peripheral Treg and TGF-beta acts as a bridge between the immune system and the
      nervous system. Neurological events mediated by the SNS, such as a stress
      response, may affect the number of T cells that regulate an immune response.
      Additionally, targeting Tregs via the SNS may be a novel approach to the
      prevention or treatment of autoimmune diseases.

PMID- 19741162
TI  - Insulin resistance and altered systemic glucose metabolism in mice lacking Nur77.
AB  - OBJECTIVE: Nur77 is an orphan nuclear receptor with pleotropic functions.
      Previous studies have identified Nur77 as a transcriptional regulator of glucose
      utilization genes in skeletal muscle and gluconeogenesis in liver. However, the
      net functional impact of these pathways is unknown. To examine the consequence of
      Nur77 signaling for glucose metabolism in vivo, we challenged Nur77 null mice
      with high-fat feeding. RESEARCH DESIGN AND METHODS: Wild-type and Nur77 null mice
      were fed a high-fat diet (60% calories from fat) for 3 months. We determined
      glucose tolerance, tissue-specific insulin sensitivity, oxygen consumption,
      muscle and liver lipid content, muscle insulin signaling, and expression of
      glucose and lipid metabolism genes. RESULTS: Mice with genetic deletion of Nur77
      exhibited increased susceptibility to diet-induced obesity and insulin
      resistance. Hyperinsulinemic-euglycemic clamp studies revealed greater high-fat
      diet-induced insulin resistance in both skeletal muscle and liver of Nur77 null
      mice compared with controls. Loss of Nur77 expression in skeletal muscle impaired
      insulin signaling and markedly reduced GLUT4 protein expression. Muscles lacking
      Nur77 also exhibited increased triglyceride content and accumulation of multiple
      even-chained acylcarnitine species. In the liver, Nur77 deletion led to hepatic
      steatosis and enhanced expression of lipogenic genes, likely reflecting the
      lipogenic effect of hyperinsulinemia. CONCLUSIONS: Collectively, these data
      demonstrate that loss of Nur77 influences systemic glucose metabolism and
      highlight the physiological contribution of muscle Nur77 to this regulatory
      pathway.

PMID- 19741163
TI  - Additive effects of genetic variation in GCK and G6PC2 on insulin secretion and
      fasting glucose.
AB  - OBJECTIVE: Glucokinase (GCK) and glucose-6-phosphatase catalytic subunit 2
      (G6PC2) regulate the glucose-cycling step in pancreatic beta-cells and may
      regulate insulin secretion. GCK rs1799884 and G6PC2 rs560887 have been
      independently associated with fasting glucose, but their interaction on glucose
      insulin relationships is not well characterized. RESEARCH DESIGN AND METHODS: We
      tested whether these variants are associated with diabetes-related quantitative
      traits in Mexican Americans from the BetaGene Study and attempted to replicate
      our findings in Finnish men from the METabolic Syndrome in Men (METSIM) Study.
      RESULTS: rs1799884 was not associated with any quantitative trait (corrected P >
      0.1), whereas rs560887 was significantly associated with the oral glucose
      tolerance test 30-min incremental insulin response (30' Deltainsulin, corrected P
      = 0.021). We found no association between quantitative traits and the
      multiplicative interaction between rs1799884 and rs560887 (P > 0.26). However,
      the additive effect of these single nucleotide polymorphisms was associated with
      fasting glucose (corrected P = 0.03) and 30' Deltainsulin (corrected P = 0.027).
      This additive association was replicated in METSIM (fasting glucose, P = 3.5 x
      10(-10) 30' Deltainsulin, P = 0.028). When we examined the relationship between
      fasting glucose and 30' Deltainsulin stratified by GCK and G6PC2, we noted
      divergent changes in these quantitative traits for GCK but parallel changes for
      G6PC2. We observed a similar pattern in METSIM. CONCLUSIONS: Our data suggest
      that variation in GCK and G6PC2 have additive effects on both fasting glucose and
      insulin secretion.

PMID- 19741164
TI  - SIRT1 genetic variation is related to BMI and risk of obesity.
AB  - OBJECTIVE: SIRT1 has pleiotropic metabolic functions. We investigated whether
      SIRT1 genetic variation is associated with obesity. RESEARCH DESIGN AND METHODS:
      In 6,251 elderly subjects from the prospective, population-based Rotterdam Study,
      three single nucleotide polymorphisms (SNPs) in the SIRT1 gene were studied in
      relation to BMI and risk of obesity (BMI > or =30 kg/m(2)) and prospectively with
      BMI change after 6.4 years of follow-up. We used cross-sectional data from 2,347
      participants from the Erasmus Rucphen Family (ERF) study for replication.
      RESULTS: Minor alleles of rs7895833 (G = 20.2%) and rs1467568 (A = 36.8%) were
      associated with lower BMI in the Rotterdam Study (P = 0.02 and 0.04) and in the
      replication cohort ERF study (P = 0.03 and 0.008) and in both studies combined (P
      = 0.002 for both SNPs), with a 0.2-0.4 kg/m(2) decrease in BMI per allele copy.
      Carriers of these alleles had 13-18% decreased risk of obesity (for rs7895833 in
      the Rotterdam Study: odds ratio 0.79 [95% CI 0.67-0.94], P = 0.007; in the ERF
      study: 0.93 [0.73-1.19], P = 0.37; and in the studies combined 0.87 [0.77-0.97],
      P = 0.02; for rs1467568 in the Rotterdam Study: 0.80 [0.68-0.94], P = 0.007; in
      the ERF study: 0.85 [0.72-0.99], P = 0.04; and in the studies combined: 0.82
      [0.73-0.92], P = 0.0009). In the Rotterdam Study, the two variants were also
      associated with a lower BMI increase during 6.4 years of follow-up (P = 0.01 and
      0.08). CONCLUSIONS: Two common variants in SIRT1 are associated with lower BMI in
      two independent Dutch populations. Carriers of these variants have 13-18%
      decreased risk of obesity and gain less weight over time. The availability of
      SIRT1 stimulators makes these findings relevant in light of the growing obesity
      epidemic.

PMID- 19741165
TI  - Transgenically induced GAD tolerance curtails the development of early beta-cell
      autoreactivities but causes the subsequent development of supernormal
      autoreactivities to other beta-cell antigens.
AB  - OBJECTIVE: To study how tolerance to GAD65 affects the development of
      autoimmunity to other beta-cell autoantigens (beta-CAAs) in GAD65-transgenic (GAD
      tg) NOD mice. RESEARCH DESIGN AND METHODS: We used ELISPOT to characterize the
      frequency and functional phenotype of T-cell responses to GAD65 and other beta
      CAAs at different ages in GAD-tg mice and their NOD mouse littermates. RESULTS:
      In young GAD-tg mice, Th1 responses to GAD65's dominant determinants were 13-18%
      of those in young NOD mice. This coincided with a great reduction in Th1
      responses to other beta-CAAs. Evidently, GAD65-reactive T-cells are important for
      activating and/or expanding early autoreactivities in NOD mice. As GAD-tg mice
      aged, their T-cell responses to GAD65 remained low, but they developed
      supernormal splenic and pancreatic lymph node T-cell autoimmunity to other beta
      CAAs. Apparently, the elimination/impairment of many GAD65-reactive T-cells
      allowed other beta-CAA-reactive T-cells to eventually expand to a greater extent,
      perhaps by reducing competition for antigen-presenting cells, or homeostatic
      proliferation in the target tissue, which may explain the GAD-tg mouse's usual
      disease incidence. CONCLUSIONS: Transgenically induced reduction of GAD65
      autoreactivity curtailed the development of early T-cell responses to other beta
      CAAs. However, later in life, beta-CAA-reactive T-cells expanded to supernormal
      levels. These data suggest that early beta-cell autoreactivities are mutually
      dependent for support to activate and expand, while later in the disease process,
      autoantigen-specific T-cell pools can expand autonomously. These findings have
      implications for understanding type 1 diabetes immunopathogenesis and for
      designing antigen-based immunotherapeutics.

PMID- 19741166
TI  - Common genetic determinants of glucose homeostasis in healthy children: the
      European Youth Heart Study.
AB  - OBJECTIVE: The goal of this study was to investigate whether the effects of
      common genetic variants associated with fasting glucose in adults are detectable
      in healthy children. RESEARCH DESIGN AND METHODS: Single nucleotide polymorphisms
      in MTNR1B (rs10830963), G6PC2 (rs560887), and GCK (rs4607517) were genotyped in
      2,025 healthy European children aged 9-11 and 14-16 years. Associations with
      fasting glucose, insulin, homeostasis model assessment (HOMA)-insulin resistance
      (IR) and HOMA-B were investigated along with those observed for type 2 diabetes
      variants available in this study (CDKN2A/B, IGF2BP2, CDKAL1, SLC30A8, HHEX-IDE,
      and Chr 11p12). RESULTS: Strongest associations were observed for G6PC2 and
      MTNR1B, with mean fasting glucose levels (95% CI) being 0.084 (0.06-0.11) mmol/l,
      P = 7.9 x 10(-11) and 0.069 (0.04-0.09) mmol/l, P = 1.9 x 10(-7) higher per risk
      allele copy, respectively. A similar but weaker trend was observed for GCK (0.028
      [-0.006 to 0.06] mmol/l, P = 0.11). All three variants were associated with lower
      beta-cell function (HOMA-B P = 9.38 x 10(-5), 0.004, and 0.04, respectively).
      SLC30A8 (rs13266634) was the only type 2 diabetes variant associated with higher
      fasting glucose (0.033 mmol/l [0.01-0.06], P = 0.01). Calculating a genetic
      predisposition score adding the number of risk alleles of G6PC2, MTNR1B, GCK, and
      SLC30A8 showed that glucose levels were successively higher in children carrying
      a greater number of risk alleles (P = 7.1 x 10(-17)), with mean levels of 5.34
      versus 4.91 mmol/l comparing children with seven alleles (0.6% of all children)
      to those with none (0.5%). No associations were found for fasting insulin or HOMA
      IR with any of the variants. CONCLUSIONS: The effects of common polymorphisms
      influencing fasting glucose are apparent in healthy children, whereas the
      presence of multiple risk alleles amounts to a difference of >1 SD of fasting
      glucose.

PMID- 19741167
TI  - Differences in the central anorectic effects of glucagon-like peptide-1 and
      exendin-4 in rats.
AB  - OBJECTIVE: Glucagon-like peptide (GLP)-1 is a regulatory peptide synthesized in
      the gut and the brain that plays an important role in the regulation of food
      intake. Both GLP-1 and exendin (Ex)-4, a long-acting GLP-1 receptor (GLP-1r)
      agonist, reduce food intake when administered intracerebroventricularly, whereas
      Ex4 is much more potent at suppressing food intake when given peripherally. It
      has generally been hypothesized that this difference is due to the relative
      pharmacokinetic profiles of GLP-1 and Ex4, but it is possible that the two
      peptides control feeding via distinct mechanisms. RESEARCH DESIGN AND METHODS: In
      this study, the anorectic effects of intracerebroventricular GLP-1 and Ex4, and
      the sensitivity of these effects to GLP-1r antagonism, were compared in rats. In
      addition, the GLP-1r dependence of the anorectic effect of
      intracerebroventricular Ex4 was assessed in GLP-1r(-/-) mice. RESULTS:
      Intracerebroventricular Ex4 was 100-fold more potent than GLP-1 at reducing food
      intake, and this effect was insensitive to GLP-1r antagonism. However, GLP-1r
      antagonists completely blocked the anorectic effect of intraperitoneal Ex4.
      Despite the insensitivity of intracerebroventricular Ex4 to GLP-1r antagonism,
      intracerebroventricular Ex4 failed to reduce food intake in GLP-1r(-/-) mice.
      CONCLUSIONS: These data suggest that although GLP-1rs are required for the
      actions of Ex4, there appear to be key differences in how GLP-1 and Ex4 interact
      with central nervous system GLP-1r and in how Ex4 interacts with GLP-1r in the
      brain versus the periphery. A better understanding of these unique differences
      may lead to expansion and/or improvement of GLP-1-based therapies for type 2
      diabetes and obesity.

PMID- 19741168
TI  - Rabies DNA vaccine encoding lysosome-targeted glycoprotein supplemented with
      Emulsigen-D confers complete protection in preexposure and postexposure studies
      in BALB/c mice.
AB  - The worldwide incidence of rabies and the inability of currently used vaccination
      strategies to provide highly potent and cost-effective therapy indicate the need
      for an improved rabies vaccine. Thus, DNA vaccine based on lysosome-targeted
      glycoprotein of the rabies virus was evaluated in BALB/c mice. It imparted
      partial protection (60%) against challenge with 20 LD(50) of the challenge virus
      standard (CVS) strain of rabies virus. To improve the outcome of vaccination, to
      ultimately enhance the immune response, we investigated different routes for DNA
      vaccine delivery, varied doses of DNA, and the influence of adjuvant
      supplementation. The highest immune response pertaining to IgG antibody titer,
      with a predominantly IgG1/IgG2a subclass distribution, effective cellular
      immunity, and a high level of rabies virus neutralizing antibodies (RVNAs) was
      attained by the optimized DNA vaccine formulation comprising intramuscular
      administration of 100 microg of DNA vaccine supplemented with Emulsigen-D. In
      preexposure prophylaxis, a 3-dose regimen of this formulation generated a high
      RVNA titer (32 IU/ml) and conferred complete protection against challenge with 20
      LD(50) of CVS. For postexposure efficacy analysis, rabies was experimentally
      induced with 50 LD(50) of CVS. Subsequent therapy with 5 doses of the formulation
      completely prevented rabies in BALB/c mice, which maintained protective RVNA
      titers of 4 IU/ml. The World Health Organization recommended rabies protective
      titer threshold is 0.5 IU/ml. Thus, this optimized DNA vaccine formulation
      provides an avenue for preventing and controlling rabies.

PMID- 19741169
TI  - Competing discrete interfacial effects are critical for amyloidogenesis.
AB  - Amyloid accumulation is associated with pathological conditions, including type
      II diabetes and Alzheimer's disease. Lipids influence amyloidogenesis and are
      themselves targets for amyloid-mediated cell membrane disruption. Amyloid
      precursors are surface-active, accumulating at hydrophobic-hydrophilic interfaces
      (e.g., air-water), where their biophysical and kinetic behaviors differ from
      those in the bulk solution with significant and underappreciated consequences.
      Biophysical modeling predicted the probability and rate of beta-sheet amyloid
      dimer formation to be higher and faster at the air-water interface (AWI) than in
      the bulk (by 14 and approximately 1500 times, respectively). Time-course staining
      experiments with a typical amyloid dye verified our predictions by demonstrating
      that without AWI, islet amyloid polypeptide (IAPP) fibrilization was abolished or
      slowed, depending on the conditions. Our controls included undisturbed IAPP
      reactions, and we ascertained that the AWI removal process (technical or
      material) did not itself affect the reaction. Furthermore, we showed that the
      role of membranes in amyloidogenesis has been previously underestimated; in an in
      vivo-like situation (with no AWI), anionic liposomes (containing
      dioleoylphosphatidylglycerol) enhanced IAPP fibrilogenesis far more than
      described previously in conventional assay conditions (in the presence of an
      AWI). These findings have implications for the protein misfolding field and in
      assay design to target toxic protein aggregation.

PMID- 19741170
TI  - iNOS-derived nitric oxide mediates the increase in TFF2 expression associated
      with gastric damage: role of HIF-1.
AB  - Trefoil (TFF) peptides are involved in gastrointestinal mucosal restitution. An
      hypoxia inducible factor 1 (HIF-1)-dependent induction of TFF genes has been
      reported in gastric epithelial cells. Nitric oxide (NO) is associated with
      mucosal damage and modulates HIF-1 activity. The aim of the present study was to
      analyze the role of iNOS-derived NO in HIF-1alpha stabilization and TFF gene
      expression in damaged gastric mucosa. Aspirin caused gastric injury that peaked 6
      h after dosing and returned to normality at 24 h. iNOS mRNA expression occurs in
      the corpus in parallel with damage. Blockade of iNOS activity did not modify
      gastric lesions induced by aspirin but delayed mucosal healing. Aspirin induced
      HIF-1alpha stabilization and TFF2 mRNA up-regulation in the mucosa, but these
      effects were diminished when iNOS activity was inhibited. Results obtained using
      a coculture setup showed that iNOS-derived NO from activated macrophages induced
      HIF-1alpha stabilization, TFF gene expression, and accelerated wound healing in
      cultured epithelial cells. Finally, transient silencing of endogenous HIF-1alpha
      in epithelial cells significantly undermined activated macrophage-induced TFF
      gene expression. Evidence suggests that the iNOS-derived NO associated with NSAID
      induced gastric injury is implicated in mucosal restitution via the HIF-1
      mediated induction of TFF genes.

PMID- 19741171
TI  - Vitamin C restores healthy aging in a mouse model for Werner syndrome.
AB  - Werner syndrome (WS) is a premature aging disorder caused by mutations in a RecQ
      like DNA helicase. Mice lacking the helicase domain of the WRN homologue exhibit
      many phenotypic features of WS, including a prooxidant status and a shorter mean
      life span compared to wild-type animals. Here, we show that Wrn mutant mice also
      develop premature liver sinusoidal endothelial defenestration along with
      inflammation and metabolic syndrome. Vitamin C supplementation rescued the
      shorter mean life span of Wrn mutant mice and reversed several age-related
      abnormalities in adipose tissues and liver endothelial defenestration, genomic
      integrity, and inflammatory status. At the molecular level, phosphorylation of
      age-related stress markers like Akt kinase-specific substrates and the
      transcription factor NF-kappaB, as well as protein kinase Cdelta and Hif-1alpha
      transcription factor levels, which are increased in the liver of Wrn mutants,
      were normalized by vitamin C. Vitamin C also increased the transcriptional
      regulator of lipid metabolism PPARalpha. Finally, microarray and gene set
      enrichment analyses on liver tissues revealed that vitamin C decreased genes
      normally up-regulated in human WS fibroblasts and cancers, and it increased genes
      involved in tissue injury response and adipocyte dedifferentiation in obese mice.
      Vitamin C did not have such effect on wild-type mice. These results indicate that
      vitamin C supplementation could be beneficial for patients with WS.

PMID- 19741172
TI  - Activation of native TRPC3 cation channels by phospholipase D.
AB  - In the mammalian nervous system, stimulation of G-protein-coupled type I
      glutamate receptors triggers various forms of neuronal plasticity, including
      cerebellar long-term depression and hippocampal long-term potentiation.
      Activation of these receptors in the cerebellum also leads to a slow excitatory
      postsynaptic current mediated by nonselective TRPC3 cation channels. How TRPC3
      channels are opened is unknown, although it is widely thought that channel gating
      requires phospholipase C activation. Using the patch-clamp technique and
      immunohistochemistry in rat cerebellar slices, we show that metabotropic
      glutamate receptors activate TRPC3 channels through the small GTP-binding protein
      Rho and subsequent phospholipase D stimulation. TRPC3 channel gating is
      independent of phospholipase C activity. These results reveal a new mechanism for
      the gating of the ubiquitous TRPC3 channel and identify a key role for
      phospholipase D in the generation of the slow excitatory postsynaptic current in
      cerebellar Purkinje cells.

PMID- 19741173
TI  - Adipocyte size predicts incidence of type 2 diabetes in women.
AB  - Enlarged subcutaneous abdominal adipocytes have been shown to predict incidence
      of type 2 diabetes (T2D) in the Pima population of Arizona (USA). We investigated
      the role of subcutaneous abdominal adipocyte size (AAS), as well as femoral
      adipocyte size (FAS), as predictors of T2D in a population-based Swedish cohort.
      In 1974-1975, a sample of 1302 middle-aged women underwent a health examination,
      including anthropometry and evaluation of parental medical history. In addition,
      body composition (total body potassium and total body water), AAS and FAS
      (adipose tissue needle biopsy) were assessed in a subsample of 245 women.
      Incidence of T2D was followed until 2001, with 36 cases eligible for inclusion in
      this analysis. Women developing T2D had larger AAS at baseline vs. women
      remaining healthy (age/heredity-adjusted hazard ratio for increase of AAS by 1 sd
      [AAS-HR] 1.91; P<0.001). Further adjustment for both body fat percentage and
      waist-to-height ratio (WHtR) indicated a robust association. For FAS, the
      corresponding associations were consistently weaker. WHtR retained a strong
      predictive association independent of AAS and FAS (WHtR-HR 2.6 and 2.7,
      respectively; P<0.001). To conclude, in addition to the amount and distribution
      of body fat in women, subcutaneous adipocyte size, particularly in the abdominal
      region, predicts incidence of T2D in later life.

PMID- 19741174
TI  - The nature of evidence.

PMID- 19741175
TI  - Asymmetric headgear for differential molar movement: a study using finite element
      analysis.
AB  - OBJECTIVE: To compare the effects of four different asymmetric headgear systems.
      DESIGN: A mathematical method for three-dimensional data called finite element
      analysis. SETTING: The Orthodontic Department, the Federal University of Rio de
      Janeiro and the Metallurgical Engineering Department of the Fluminense Federal
      University. METHODS: Four systems of delivering an asymmetrical force to headgear
      were studied: using face-bow arms of different lengths, a symmetric face-bow with
      one of the arms bent outward in relation to the internal arch, a symmetric face
      bow used in combination with a transpalatal arch activated to produce an
      asymmetric force, and a symmetric face-bow with the outer bow soldered to the
      inner bow on the side where a larger force will be applied. RESULTS: All four
      systems were effective in promoting asymmetric distal movement of the molars.
      However, the symmetrical face-bow with the outer bow soldered to the inner bow
      (system 4) could be used in asymmetric mechanics if the bows are soldered on the
      opposite side to the proposed distalization. Lateral and occlusal displacing
      forces were observed in all systems as well as tip-back and rotational movements.
      CONCLUSION: The simulated computer model used in this investigation suggests that
      a face-bow with a symmetrically soldered joint and arms of equal lengths used in
      combination with a transpalatal arch is the best headgear option when asymmetric
      movement of upper molars is desired.

PMID- 19741176
TI  - Aesthetic impact of malocclusion in the daily living of Brazilian adolescents.
AB  - OBJECTIVE: The aim of the present study was to determine the biopsychosocial
      impact of malocclusion on the daily living of Brazilian adolescents (14 to 18
      years of age) through normative and subjective records and identify factors
      directly involved in the self-perception of malocclusions. DESIGN: Cross
      sectional. SETTING: Public and private schools in the city of Belo Horizonte,
      Brazil. SUBJECTS AND METHODS: The sample was made up of 403 adolescents, with no
      prior history of orthodontic treatment, who were selected randomly from a
      population of 182,291 students in the same age range. The oral impact of
      malocclusion was assessed using the Oral Impact on Daily Performance (OIDP),
      whereas clinical criteria were assessed using the Dental Aesthetic Index (DAI).
      Self-perception of dental aesthetics was assessed using the Oral Aesthetic
      Subjective Impact Scale (OASIS) and self-esteem was assessed using the Global
      Negative Self-Evaluation (GSE) scale. Other variables were assessed using
      questionnaires. The chi-square test, simple and multiple logistic regression
      analyses were used for the statistical analysis. RESULTS: Ninety five adolescents
      (24%) reported feeling embarrassed to smile (aesthetic impact). A logistic
      regression suggested that the following variables were directly involved in the
      self-perception of malocclusion: upper anterior crowding > or = 2 mm (P=0.009),
      median diastema > or = 2 mm (P=0.040), normative treatment need (highly
      desirable) (P<0.001) and low economic level (P<0.001). CONCLUSION: Negative
      repercussions on daily living were found in Brazilian adolescents with
      malocclusions affecting anterior dental aesthetics.

PMID- 19741177
TI  - Nasal morphology as an indicator of vertical maxillary skeletal pattern.
AB  - OBJECTIVE: To investigate the relationship between nasal morphology and vertical
      maxillary skeletal pattern. DESIGN: A retrospective study. SETTING: Department of
      Orthodontics and Dentofacial Orthopaedics, Armed Forces Medical College, Pune,
      India. SUBJECTS AND METHODS: The sample included the lateral cephalometric
      radiographs of 190 Indian adults (103 women, 87 men), aged 18 to 27 years with no
      previous history of trauma, surgical intervention, congenital disease or
      orthodontic treatment. Seven skeletal parameters of vertical facial growth and
      six nasal parameters were measured. RESULTS: There was a significant correlation
      between vertical maxillary skeletal and soft tissue nasal parameters. Nasal
      length significantly correlated with upper anterior facial height (r=0.850,
      P<0.001) and inclination of palatal plane (r=0.433, P<0.001). Upward nasal tip
      inclination showed a significant negative correlation with inclination of the
      palatal plane (r=-0.462, P<0.001). CONCLUSION: The clinical significance of this
      study is that the nasolabial angle in itself may not reflect a midface vertical
      discrepancy, however its upper component, i.e. the degree of upturn of the nose
      with decreased nasal length in an adult subject may indicate an underlying change
      in inclination of the palatal plane. This might be of value during orthodontic
      diagnosis and treatment planning.

PMID- 19741178
TI  - An evaluation of the effects of a web-based modular teaching programme, housed
      within a virtual learning environment on orthodontic training for specialist
      registrars.
AB  - OBJECTIVES: A new modular teaching programme, housed within a virtual learning
      environment (VLE) was introduced in Bristol in 2004 to complement the academic
      training of orthodontic postgraduates. The aims of this study were to evaluate
      whether its introduction had reduced travel commitments for trainees, reduced
      demands on academic staff and whether it had any effect on teaching and learning.
      DESIGN: An investigative mixed methods study designed to collect and analyse
      verbal and written data. SETTING: The South West Region of the UK. SUBJECTS AND
      METHODS: Semi-structured interviews and focus groups with nine trainees and 14
      trainers were taped and transcribed. Written data were coded and analysed
      thematically. The qualitative data from interviews and focus groups were
      complemented with written data from trainee diaries and a limited amount of
      quantitative data collected from the VLE. CONCLUSIONS: Travel commitments for
      trainees have reduced as a result of introducing the web-based resource, but not
      as expected. Demands on academic staff have not reduced but have changed. The
      resource has had positive effects on postgraduate orthodontic teaching and
      learning. Important themes of interest emerging from the data are improvements in
      the flexibility and efficiency of learning and the value of the resource as a
      repository of information and in the organization of teaching and learning.
      Despite the popularity of this web based learning resource, trainees continue to
      value the opportunity to interact face to face with their teachers and peers and
      are prepared to travel for organized teaching sessions.

PMID- 19741179
TI  - Colour changes of orthodontic elastomeric module materials exposed to in vitro
      dietary media.
AB  - OBJECTIVE: To evaluate the colour stability of orthodontic elastomeric module
      material exposed to dietary media. DESIGN: An in vitro laboratory study.
      MATERIALS AND METHODS: Coloured and clear orthodontic elastomeric modules from
      four companies were exposed to coffee, cola, tea and spices for 72 h. The
      difference in colour components was measured with a Minolta chromameter before
      and after exposure. RESULTS: Significant changes in colour, including grey level
      and chromaticity, both as a function of colour and company of elastomeric
      ligature module were found following exposure to beverages and spices. Colour
      change was most affected by Deltab* (yellowness) and most significant in clear
      modules. Modules made using injection mouldings were more resistant to colour
      change than those by extrusion. Spice mix had the most effect and cola beverage
      the least. Clinically, these changes compromised both colour stability and
      esthetics of the elastomeric module. CONCLUSIONS: Clinicians should make patients
      aware of the effect of consuming beverages and spices on the colour stability of
      their selected ligature modules. Clinicians should favour modules made with
      injection moulding. Darker colour modules may be preferred to clear modules to
      avoid excessive colour degradation through dietary media such as beverages and
      food spices. Patients consuming large amounts of spices or coffee should avoid
      clear modules made by extrusion processing because of their tendency to
      discolour.

PMID- 19741180
TI  - Infraocclusion of secondary deciduous molars--an unusual outcome.
AB  - Infraocclusion is a condition frequently associated with primary molars. The
      infraoccluded primary teeth remain in a fixed position, while the teeth adjacent
      to them continue to erupt, moving occlusally. It is generally accepted that the
      cause of the altered occlusal level is ankylosis of the affected tooth. This
      report describes a case in which a short course of interceptive treatment with a
      2 x 4 fixed appliance resulted in resolution of the infrocclusion. Recreating
      space for a severely infraoccluded second deciduous molar resulted in 'eruption'
      of the tooth without the need for extraction.

PMID- 19741181
TI  - Optragate oral retractor.
AB  - This paper illustrates an innovation in oral retraction developed for use in
      general dentistry. The benefits for use in orthodontic bonding are described.

PMID- 19741182
TI  - New developments in tooth whitening. The current status of external bleaching in
      orthodontics.
AB  - This article provides a contemporary view of external tooth whitening procedures
      currently available, with particular reference to bleaching. The various
      techniques and products are described, with their advantages, disadvantages, mode
      of action and the current legal stand-point discussed. The results of a British
      Orthodontic Society survey of Specialist and Practitioner Groups regarding
      current usage patterns of tooth whitening products are presented.

PMID- 19741183
TI  - Cone beam computed tomography: a useful tool in orthodontic diagnosis and
      treatment planning.
AB  - The aim of this article is to make clinicians aware of the use of cone beam
      computed tomography (CBCT) within the field of orthodontics. The paper describes
      five cases each one illustrating the improved diagnostic yield using CBCT over
      conventional radiography thus facilitating the appropriate treatment planning of
      patients.

PMID- 19741184
TI  - Postpartum diabetes screening: adherence rate and the performance of fasting
      plasma glucose versus oral glucose tolerance test.
AB  - OBJECTIVE: To determine the rate of adherence to postpartum glycemic testing in
      women with gestational diabetes mellitus (GDM) and the performance of fasting
      plasma glucose (FPG) versus the 75-g oral glucose tolerance test (OGTT) in
      detecting postpartum glucose intolerance. RESEARCH DESIGN AND METHODS: The study
      was a retrospective cohort of 1,006 women with GDM attending a pregnancy diabetes
      clinic. RESULTS: Postpartum screening was completed in 438 (48%) women. Women
      nonadherent to testing had higher parity (1.10 vs. 0.87) and were less likely to
      require insulin for management of their GDM. Among women who were tested, 89
      (21%) had an abnormal result, only 25 (28%) of whom were identified by FPG.
      Factors associated with abnormal postpartum diabetes screening include non
      Caucasian ethnicity, previous GDM, higher A1C, and OGTT values during pregnancy
      and treatment with insulin. CONCLUSIONS: The rate of postpartum diabetes
      screening is low, and FPG lacks sensitivity as a screening test in comparison
      with OGTT.

PMID- 19741185
TI  - Aspirin for the primary prevention of cardiovascular events: a systematic review
      and meta-analysis comparing patients with and without diabetes.
AB  - OBJECTIVE: The negative results of two randomized controlled trials (RCTs) have
      challenged current guideline recommendations for using aspirin for primary
      prevention of cardiovascular events among patients with diabetes. We therefore
      sought to determine if the effect of aspirin for primary prevention of
      cardiovascular events and mortality differs between patients with and without
      diabetes. RESEARCH DESIGN AND METHODS: We conducted a systematic search of
      MEDLINE, EMBASE, Cochrane Library, Web of Science, and Scopus since their
      inceptions until November 2008 for RCTs of aspirin for primary prevention of
      cardiovascular events. Blinded pairs of reviewers evaluated studies and extracted
      data. Random-effects meta-analysis and Bayesian logistic regression were used to
      estimate the ratios of relative risks (RRs) of outcomes of interest among
      patients with and without diabetes. A 95% CI that crosses 1.00 indicates that the
      effect of aspirin does not differ between patients with and without diabetes.
      RESULTS: Nine RCTs with moderate to high methodological quality contributed data
      to the analyses. The ratios of RRs comparing the benefit of aspirin among
      patients with diabetes compared with patients without diabetes for mortality,
      myocardial infarction, and ischemic stroke were 1.12 (95% CI 0.92-1.35), 1.19
      (0.82-1.17), and 0.70 (0.25-1.97), respectively. CONCLUSIONS: Whereas estimates
      of benefit among patients with diabetes remain imprecise, our analysis suggests
      that the relative benefit of aspirin is similar in patients with and without
      diabetes.

PMID- 19741186
TI  - Emphasis on carbohydrates may negatively influence dietary patterns in youth with
      type 1 diabetes.
AB  - OBJECTIVE: To assess perceptions of healthful eating and the influence of
      diabetes management on dietary behaviors among youth with type 1 diabetes and
      parents. RESEARCH DESIGN AND METHODS: Youth with type 1 diabetes (n = 35), ages 8
      21 years, and parents participated in focus groups. Focus group recordings were
      transcribed and coded into themes. Clinical data were abstracted from the
      electronic medical record. RESULTS: Central topics were perceptions of healthful
      eating and the impact of diabetes management on diet. An emphasis on limiting
      postprandial glycemic excursions occasionally contradicted the traditional
      perception of healthful eating, which emphasized consumption of nutrient-dense
      whole foods in favor of prepackaged choices. Whereas fixed regimens required more
      rigid diets, basal-bolus regimens provided more opportunities for unhealthful
      eating. Most youth perceived "refined" grains as more healthful grains.
      CONCLUSIONS: For youth with type 1 diabetes and parents, an emphasis on
      carbohydrate quantity over quality may distort beliefs and behaviors regarding
      healthful eating.

PMID- 19741187
TI  - Addressing literacy and numeracy to improve diabetes care: two randomized
      controlled trials.
AB  - OBJECTIVE: Diabetic patients with lower literacy or numeracy skills are at
      greater risk for poor diabetes outcomes. This study evaluated the impact of
      providing literacy- and numeracy-sensitive diabetes care within an enhanced
      diabetes care program on A1C and other diabetes outcomes. RESEARCH DESIGN AND
      METHODS: In two randomized controlled trials, we enrolled 198 adult diabetic
      patients with most recent A1C >or=7.0%, referred for participation in an enhanced
      diabetes care program. For 3 months, control patients received care from existing
      enhanced diabetes care programs, whereas intervention patients received enhanced
      programs that also addressed literacy and numeracy at each institution.
      Intervention providers received health communication training and used the
      interactive Diabetes Literacy and Numeracy Education Toolkit with patients. A1C
      was measured at 3 and 6 months follow-up. Secondary outcomes included self
      efficacy, self-management behaviors, and treatment satisfaction. RESULTS: At 3
      months, both intervention and control patients had significant improvements in
      A1C from baseline (intervention -1.50 [95% CI -1.80 to -1.02]; control -0.80 [
      1.10 to -0.30]). In adjusted analysis, there was greater improvement in A1C in
      the intervention group than in the control group (P = 0.03). At 6 months, there
      were no differences in A1C between intervention and control groups. Self-efficacy
      improved from baseline for both groups. No significant differences were found for
      self-management behaviors or satisfaction. CONCLUSIONS: A literacy- and numeracy
      focused diabetes care program modestly improved self-efficacy and glycemic
      control compared with standard enhanced diabetes care, but the difference
      attenuated after conclusion of the intervention.

PMID- 19741188
TI  - Effects of a plant-based high-carbohydrate/high-fiber diet versus high
      monounsaturated fat/low-carbohydrate diet on postprandial lipids in type 2
      diabetic patients.
AB  - OBJECTIVE: To search for a better dietary approach to treat postprandial lipid
      abnormalities and improve glucose control in type 2 diabetic patients. RESEARCH
      DESIGN AND METHODS: According to a randomized crossover design, 18 type 2
      diabetic patients (aged 59 +/- 5 years; BMI 27 +/- 3 kg/m(2)) (means +/- SD) in
      satisfactory blood glucose control on diet or diet plus metformin followed a diet
      relatively rich in carbohydrates (52% total energy), rich in fiber (28 g/1,000
      kcal), and with a low glycemic index (58%) (high-carbohydrate/high-fiber diet) or
      a diet relatively low in carbohydrate (45%) and rich in monounsaturated fat (23%)
      (low-carbohydrate/high-monounsaturated fat diet) for 4 weeks. Thereafter, they
      shifted to the other diet for 4 more weeks. At the end of each period, plasma
      glucose, insulin, lipids, and lipoprotein fractions (separated by discontinuous
      density gradient ultracentrifugation) were determined on blood samples taken at
      fasting and over 6 h after a test meal having a similar composition as the
      corresponding diet. RESULTS: In addition to a significant decrease in
      postprandial plasma glucose, insulin responses, and glycemic variability, the
      high-carbohydrate/high-fiber diet also significantly improved the primary end
      point, since it reduced the postprandial incremental areas under the curve
      (IAUCs) of triglyceride-rich lipoproteins, in particular, chylomicrons
      (cholesterol IAUC: 0.05 +/- 0.01 vs. 0.08 +/- 0.02 mmol/l per 6 h; triglycerides
      IAUC: 0.71 +/- 0.35 vs. 1.03 +/- 0.58 mmol/l per 6 h, P < 0.05). CONCLUSIONS: A
      diet rich in carbohydrate and fiber, essentially based on legumes, vegetables,
      fruits, and whole cereals, may be particularly useful for treating diabetic
      patients because of its multiple effects on different cardiovascular risk
      factors, including postprandial lipids abnormalities.

PMID- 19741189
TI  - Pancreatic islet autoantibodies as predictors of type 1 diabetes in the Diabetes
      Prevention Trial-Type 1.
AB  - OBJECTIVE: There is limited information from large-scale prospective studies
      regarding the prediction of type 1 diabetes by specific types of pancreatic islet
      autoantibodies, either alone or in combination. Thus, we studied the extent to
      which specific autoantibodies are predictive of type 1 diabetes. RESEARCH DESIGN
      AND METHODS: Two cohorts were derived from the first screening for islet cell
      autoantibodies (ICAs) in the Diabetes Prevention Trial-Type 1 (DPT-1).
      Autoantibodies to GAD 65 (GAD65), insulinoma-associated antigen-2 (ICA512), and
      insulin (micro-IAA [mIAA]) were also measured. Participants were followed for the
      occurrence of type 1 diabetes. One cohort (Questionnaire) included those who did
      not enter the DPT-1 trials, but responded to questionnaires (n = 28,507, 2.4%
      ICA(+)). The other cohort (Trials) included DPT-1 participants (n = 528, 83.3%
      ICA(+)). RESULTS: In both cohorts autoantibody number was highly predictive of
      type 1 diabetes (P < 0.001). The Questionnaire cohort was used to assess
      prediction according to the type of autoantibody. As single autoantibodies, ICA
      (3.9%), GAD65 (4.4%), and ICA512 (4.6%) were similarly predictive of type 1
      diabetes in proportional hazards models (P < 0.001 for all). However, no subjects
      with mIAA as single autoantibodies developed type 1 diabetes. As second
      autoantibodies, all except mIAA added significantly (P < 0.001) to the prediction
      of type 1 diabetes. Within the positive range, GAD65 and ICA autoantibody titers
      were predictive of type 1 diabetes. CONCLUSIONS: The data indicate that the
      number of autoantibodies is predictive of type 1 diabetes. However, mIAA is less
      predictive of type 1 diabetes than other autoantibodies. Autoantibody number,
      type of autoantibody, and autoantibody titer must be carefully considered in
      planning prevention trials for type 1 diabetes.

PMID- 19741190
TI  - How I treat postthrombotic syndrome.
AB  - Postthrombotic syndrome (PTS) is a chronic complication of deep venous thrombosis
      (DVT) that reduces quality of life and has important socioeconomic consequences.
      More than one-third of patients with DVT will develop PTS, and 5% to 10% of
      patients will develop severe PTS, which may manifest as venous ulceration. The
      principal risk factors for PTS are persistent leg symptoms 1 month after the
      acute episode of DVT, extensive DVT, recurrent ipsilateral DVT, obesity, and
      older age. Daily use of elastic compression stockings (ECSs) for 2 years after
      proximal DVT appears to reduce the risk of PTS; however, there is uncertainty
      about optimal duration of use and compression strength of ECSs and the magnitude
      of their effect. The cornerstone of managing PTS is compression therapy,
      primarily using ECSs. Venoactive medications such as aescin and rutoside may
      provide short-term relief of PTS symptoms. The likelihood of developing PTS after
      DVT should be discussed with patients, and symptoms and signs of PTS should be
      monitored during clinical follow-up. Further studies to elucidate the
      pathophysiology of PTS, to identify clinical and biologic risk factors, and to
      test new preventive and therapeutic approaches to PTS are needed to ultimately
      improve the long-term prognosis of patients with DVT.

PMID- 19741191
TI  - Human platelets produced in nonobese diabetic/severe combined immunodeficient
      (NOD/SCID) mice upon transplantation of human cord blood CD34(+) cells are
      functionally active in an ex vivo flow model of thrombosis.
AB  - Xenotransplantation systems have been used with increasing success to better
      understand human hematopoiesis and thrombopoiesis. In this study, we demonstrate
      that production of human platelets in nonobese diabetic/severe combined
      immunodeficient mice after transplantation of unexpanded cord-blood CD34(+) cells
      was detected within 10 days after transplantation, with the number of circulating
      human platelets peaking at 2 weeks (up to 87 x 10(3)/microL). This rapid human
      platelet production was followed by a second wave of platelet formation 5 weeks
      after transplantation, with a population of 5% still detected after 8 weeks,
      attesting for long-term engraftment. Platelets issued from human hematopoietic
      stem cell progenitors are functional, as assessed by increased CD62P expression
      and PAC1 binding in response to collagen-related peptide and thrombin receptor
      activating peptide activation and their ability to incorporate into thrombi
      formed on a collagen-coated surface in an ex vivo flow model of thrombosis. This
      interaction was abrogated by addition of inhibitory monoclonal antibodies against
      human glycoprotein Ibalpha (GPIbalpha) and GPIIb/IIIa. Thus, our mouse model with
      production of human platelets may be further explored to study the function of
      genetically modified platelets, but also to investigate the effect of stimulators
      or inhibitors of human thrombopoiesis in vivo.

PMID- 19741192
TI  - Repulsive axon guidance molecule Slit3 is a novel angiogenic factor.
AB  - Slits are large, secreted repulsive axon guidance molecules. Recent genetic
      studies revealed that the Slit3 is dispensable for neural development but
      required for non-neuron-related developmental processes, such as the genesis of
      the diaphragm and kidney. Here we report that Slit3 potently promotes
      angiogenesis, a process essential for proper organogenesis during embryonic
      development. We observed that Slit3 is expressed and secreted by both endothelial
      cells and vascular smooth muscle cells in vasculature and that the Slit cognate
      receptors Robo1 and Robo4 are universally expressed by endothelial cells,
      suggesting that Slit3 may act in paracrine and autocrine manners to regulate
      endothelial cells. Cellular function studies revealed that Slit3 stimulates
      endothelial-cell proliferation, promotes endothelial-cell motility and chemotaxis
      via interaction with Robo4, and accelerates endothelial-cell vascular network
      formation in vitro with a specific activity comparable with vascular endothelial
      growth factor. Furthermore, Slit3 stimulates neovessel sprouting ex vivo and new
      blood vessel growth in vivo. Consistent with these observations, the Slit3
      knockout mice display disrupted angiogenesis during embryogenesis. Taken
      together, our studies reveal that the repulsive axon guidance molecule Slit3 is a
      novel and potent angiogenic factor and functions to promote angiogenesis in
      coordinating organogenesis during embryonic development.

PMID- 19741193
TI  - Inherent differences in morphology, proliferation, and migration in saphenous
      vein smooth muscle cells cultured from nondiabetic and Type 2 diabetic patients.
AB  - Individuals with Type 2 diabetes mellitus (T2DM) are at increased risk of
      saphenous vein (SV) graft stenosis following coronary artery bypass. Graft
      stenosis is caused by intimal hyperplasia, a pathology characterized by smooth
      muscle cell (SMC) proliferation and migration. We hypothesized that SV-SMC from
      T2DM patients were intrinsically more proliferative and migratory than those from
      nondiabetic individuals. SV-SMC were cultured from nondiabetic and T2DM patients.
      Cell morphology (light microscopy, immunocytochemistry), S100A4 expression (real
      time RT-PCR, immunoblotting), proliferation (cell counting), migration (Boyden
      chamber assay), and cell signaling (immunoblotting with phosphorylation state
      specific antibodies) were studied. SV-SMC from T2DM patients were morphologically
      distinct from nondiabetic patients and exhibited a predominantly rhomboid
      phenotype, accompanied by disrupted F-actin cytoskeleton, disorganized alpha
      smooth muscle actin network, and increased focal adhesion formation. However, no
      differences were observed in expression of the calcium-binding protein S100A4, a
      marker of rhomboid SMC phenotype, between the two cell populations. T2DM cells
      were less proliferative in response to fetal calf serum than nondiabetic cells,
      but both populations had similar proliferative responses to insulin plus PDGF.
      Under high glucose concentration conditions in the presence of insulin, migration
      of diabetic SV-SMC was greater than nondiabetic cells. Glucose concentration did
      not affect SV-SMC proliferation. No differences in insulin or PDGF-induced
      phosphorylation of ERK-1/2 or components of the Akt pathway (Akt-Ser473, Akt
      Thr308, and GSK-3beta) were apparent between the two populations. In conclusion,
      SV-SMC from T2DM patients differ from nondiabetic SV-SMC in that they exhibit a
      rhomboid phenotype and are more migratory, but less proliferative, in response to
      serum.

PMID- 19741194
TI  - Angiotensin II type-1 receptor regulates RhoA and Rho-kinase/ROCK activation via
      multiple mechanisms. Focus on "Angiotensin II induces RhoA activation through
      SHP2-dependent dephosphorylation of the RhoGAP p190A in vascular smooth muscle
      cells".

PMID- 19741195
TI  - Hepatocyte nuclear factor 1 is essential for transcription of sodium-dependent
      vitamin C transporter protein 1.
AB  - Transport and distribution of vitamin C is primarily regulated by the function of
      sodium-dependent vitamin C transporters (SVCTs). SVCT1 is expressed in the small
      intestine, liver, and kidney, organs that play a vital role in whole body vitamin
      C homeostasis. Despite the importance of this protein, little is known about
      regulation of the gene encoding SVCT1, Slc23a1. In this study, we present the
      first investigation of the transcriptional regulation of human Slc23a1,
      identifying transcription factors that may influence its expression. A 1,239-bp
      genomic DNA fragment corresponding to the 5'-flanking region of Slc23a1 was
      isolated from a human hepatocarcinoma cell line (HepG2) and sequenced. When
      cloned into a reporter gene construct, robust transcriptional activity was seen
      in this sequence, nearly 25-fold above the control vector. Deletion analysis of
      the SVCT1 reporter gene vector defined the minimal active promoter as a small 135
      bp region upstream of the transcriptional start site. While several transcription
      factor binding sites were identified within this sequence, reporter constructs
      showed that basal transcription required the binding of hepatic nuclear factor 1
      (HNF-1) to its cognate sequence. Furthermore, mutation of this HNF-1 binding site
      resulted in complete loss of luciferase expression, even in the context of the
      whole promoter. Additionally, small interfering RNA knockdown of both members of
      the HNF-1 family, HNF-1alpha and HNF-1beta, resulted in a significant decline in
      SVCT1 transcription. Together, these data suggest that HNF-1alpha and/or HNF
      1beta binding is required for SVCT1 expression and may be involved in the
      coordinate regulation of whole body vitamin C status.

PMID- 19741197
TI  - IL-6 stimulates system A amino acid transporter activity in trophoblast cells
      through STAT3 and increased expression of SNAT2.
AB  - Changes in placental nutrient transport are closely associated with abnormal
      fetal growth. However, the molecular mechanisms underlying the regulation of
      placental amino acid transporters are unknown. We demonstrate that physiological
      concentrations of the proinflammatory cytokines interleukin (IL)-6 and tumor
      necrosis factor (TNF)-alpha stimulate the activity of amino acid transporter
      system A, but not system L, in cultured human primary trophoblast cells. Both
      cytokines increased the gene and protein expression of the Na(+)-coupled neutral
      amino acid transporter (SNAT)2 isoform and upregulated SNAT1 protein expression.
      IL-6 increased Tyr705 phosphorylation of signal transducer and activator of
      transcription 3 (STAT3). In cells transfected with small interfering RNA (siRNA)
      targeting STAT3, the RNA and protein expression of SNAT2, but not SNAT1, was
      reduced and the stimulating effect of IL-6 on system A activity was abolished.
      Despite eliciting similar responses in amino acid transport activity and
      transporter expression, TNF-alpha effects on system A activity were not mediated
      through the JAK/STAT pathway. In conclusion, we have identified a novel
      regulatory pathway involving increased gene expression of the SNAT2 isoform
      mediated by a STAT-dependent pathway, which links IL-6 to increased activity of
      system A, a ubiquitously expressed transporter of neutral amino acids. From these
      new findings, we propose that upregulation of amino acid transporters by
      cytokines may contribute to increased placental nutrient transport and fetal
      overgrowth, which are commonly found in pregnancies complicated by maternal
      diabetes and obesity.

PMID- 19741196
TI  - Loss of the apical V-ATPase a-subunit VHA-6 prevents acidification of the
      intestinal lumen during a rhythmic behavior in C. elegans.
AB  - In Caenorhabditis elegans, oscillations of intestinal pH contribute to the
      rhythmic defecation behavior, but the acid-base transport mechanisms that
      facilitate proton movement are not well understood. Here, we demonstrate that VHA
      6, an intestine-specific a-subunit of the H(+)-K(+)-ATPase complex (V-ATPase),
      resides in the apical membrane of the intestinal epithelial cells and is required
      for luminal acidification. Disruption of the vha-6 gene led to early
      developmental arrest; the arrest phenotype could be complemented by expression of
      a fluorescently labeled vha-6 transgene. To study the contribution of vha-6 to pH
      homeostasis in larval worms, we used a partial reduction of function through
      postembryonic single-generation RNA interference. We demonstrate that the
      inability to fully acidify the intestinal lumen coincides with a defect in pH
      recovery of the intestinal epithelial cells, suggesting that VHA-6 is essential
      for proton pumping following defecation. Moreover, intestinal dipeptide
      accumulation and fat storage are compromised by the loss of VHA-6, suggesting
      that luminal acidification promotes nutrient uptake in worms, as well as in
      mammals. Since acidified intracellular vesicles and autofluorescent storage
      granules are indistinguishable between the vha-6 mutant and controls, it is
      likely that the nutrient-restricted phenotype is due to a loss of plasma membrane
      V-ATPase activity specifically. These data establish a simple genetic model for
      proton pump-driven acidification. Since defecation occurs at 45-s intervals in
      worms, this model represents an opportunity to study acute regulation of V-ATPase
      activity on a short time scale and may be useful in the study of alternative
      treatments for acid-peptic disorders.

PMID- 19741198
TI  - Estradiol-mediated ERK phosphorylation and apoptosis in vascular smooth muscle
      cells requires GPR 30.
AB  - Recent studies suggest that the rapid and nongenomic effects of estradiol may be
      mediated through the G protein-coupled receptor dubbed GPR30 receptor. The
      present study examines the role of GPR30 versus a classical estrogen receptor
      (ERalpha) in mediating the growth regulatory effects of estradiol. GPR30 is
      readily detectable in freshly isolated vascular tissue but barely detectable in
      cultured vascular smooth muscle cells (VSMC). In freshly isolated aortic tissue,
      estradiol stimulated extracellular signal-regulated kinases (ERK)
      phosphorylation. In contrast, in cultured VSMC, where GPR30 expression is
      significantly reduced, estradiol inhibits ERK phosphorylation. Transfer of the
      genes encoding GPR30 led to estradiol stimulation of ERK phosphorylation, which
      is opposite the effects of estradiol in the primary culture of VSMCs.
      Transduction of the mineralocorticoid receptor (MR) had no effect on estradiol
      effects on ERK. Estradiol-mediated stimulation of ERK subsequent to heterologous
      GPR30 expression was pertussis toxin sensitive and phosphoinositide 3-kinase (PI3
      kinase) dependent; under these conditions, estradiol also inhibited protein
      kinase A (PKA). In contrast, in the absence of GPR30 expression in cultured VSMC,
      estradiol stimulated PKA activity and inhibited ERK phosphorylation. To determine
      the functional effect of GPR30 (vs. estrogen receptor expression), we assessed
      estradiol-mediated apoptosis. In the absence of GPR30 expression, estradiol
      inhibited apoptosis. This effect was enhanced with ERalpha expression. In
      contrast, with GPR30 expression, estradiol stimulated apoptosis in an ERK
      dependent manner. Thus the effect of estradiol on vascular smooth muscle cell
      apoptosis is likely dependent on the balance between ER-mediated PKA activation
      and GPR30-mediated PKA inhibition and PI3 kinase activation. Taken together, we
      postulate that modulation of GPR30 expression or activity may be an important
      determinant of the effects of estradiol in the vasculature.

PMID- 19741199
TI  - Cholinergic agonists regulate JAK2/STAT3 signaling to suppress endothelial cell
      activation.
AB  - The cholinergic anti-inflammatory pathway is a physiological mechanism that
      inhibits cytokine production and minimizes tissue injury during inflammation.
      Previous investigations revealed that cholinergic stimulation (via cholinergic
      agonists and vagus nerve stimulation) suppresses endothelial cell activation and
      leukocyte recruitment. The purpose of this study was to investigate the
      mechanisms by which cholinergic agonists (e.g., nicotine and GTS-21) regulate
      endothelial cell activation. Specifically, we examined the effects of cholinergic
      agonists on IL-6-mediated endothelial cell activation through the JAK2/STAT3
      signaling pathway. Treatment of macrovascular human umbilical vein endothelial
      cells (HUVECs) and microvascular endothelial cells (MVECs) with the cholinergic
      agonists nicotine and GTS-21 significantly reduced IL-6-mediated monocyte
      chemoattractant protein-1 (MCP-1) production and ICAM-1 expression which are
      regulated through the JAK2/STAT3 pathway. We found that treatment of endothelial
      cells with cholinergic agonists significantly reduced STAT3 activation by
      phosphorylation and DNA binding. The inhibition of STAT3 phosphorylation was
      reversed by sodium orthovanadate, an inhibitor of tyrosine phosphatases, as well
      as by NSC-87877 suggesting a SHP1/2-dependent mechanism. Further investigations
      showed that cholinergic agonists reduced the phosphorylation of JAK2, an upstream
      component of the JAK2/STAT3 pathway. Finally, we observed that nicotine and GTS
      21 treatment decreased levels of SOCS3 (suppressor of cytokine signaling; a
      regulator of the inflammatory activity of IL-6) in activated endothelial cells.
      These data demonstrate that cholinergic agonists suppress IL-6-mediated
      endothelial cell activation through the JAK2/STAT3 pathway. Our results have
      significant implications for better understanding the therapeutic potential of
      cholinergic agonists for treating IL-6 mediated inflammatory conditions.

PMID- 19741200
TI  - VEGF autoregulates its proliferative and migratory ERK1/2 and p38 cascades by
      enhancing the expression of DUSP1 and DUSP5 phosphatases in endothelial cells.
AB  - Vascular endothelial growth factor (VEGF) is a key angiogenic factor that
      regulates proliferation and migration of endothelial cells via phosphorylation of
      extracellular signal-regulated kinase-1/2 (ERK1/2) and p38, respectively. Here,
      we demonstrate that VEGF strongly induces the transcription of two dual
      specificity phosphatase (DUSP) genes DUSP1 and DUSP5 in endothelial cells. Using
      fluorescence microscopy, fluorescence lifetime imaging (FLIM), and fluorescence
      cross-correlation spectroscopy (FCCS), we found that DUSP1/mitogen-activated
      protein kinases phosphatase-1 (MKP-1) was localized in both the nucleus and
      cytoplasm of endothelial cells, where it existed in complex with p38 (effective
      dissociation constant, K(D)(eff), values of 294 and 197 nM, respectively),
      whereas DUSP5 was localized in the nucleus of endothelial cells in complex with
      ERK1/2 (K(D)(eff) 345 nM). VEGF administration affected differentially the
      K(D)(eff) values of the DUSP1/p38 and DUSP5/ERK1/2 complexes. Gain-of-function
      and lack-of-function approaches revealed that DUSP1/MKP-1 dephosphorylates
      primarily VEGF-phosphorylated p38, thereby inhibiting endothelial cell migration,
      whereas DUSP5 dephosphorylates VEGF-phosphorylated ERK1/2 inhibiting
      proliferation of endothelial cells. Moreover, DUSP5 exhibited considerable
      nuclear anchoring activity on ERK1/2 in the nucleus, thereby diminishing ERK1/2
      export to the cytoplasm decreasing its further availability for activation.

PMID- 19741201
TI  - Household food insecurity is associated with childhood malaria in rural Haiti.
AB  - Haiti is the poorest country in the Western Hemisphere and is heavily affected by
      food insecurity and malaria. To find out if these 2 conditions are associated
      with each other, we studied a convenience sample of 153 women with children 1-5 y
      old in Camp Perrin, South Haiti. Household food insecurity was assessed with the
      16-item Escala Latinoamericana y Caribena de Seguridad Alimentaria (ELCSA) scale
      previously validated in the target communities. ELCSA's reference time period was
      the 3 mo preceding the survey and it was answered by the mother. Households were
      categorized as either food secure (2%; ELCSA score = 0), food insecure/very food
      insecure (42.7%; ELCSA score range: 1-10), or severely food insecure (57.3%;
      ELCSA score range: 11-16). A total of 34.0% of women reported that their children
      had malaria during the 2 mo preceding the survey. Multivariate analyses showed
      that severe food insecure was a risk factor for perceived clinical malaria (odds
      ratio: 5.97; 95% CI: 2.06-17.28). Additional risk factors for perceived clinical
      malaria were as follows: not receiving colostrum, poor child health (via maternal
      self-report), a child BMI <17 kg/m(2), and child vitamin A supplementation more
      than once since birth. Findings suggest that policies and programs that address
      food insecurity are also likely to reduce the risk of malaria in Haiti.

PMID- 19741202
TI  - Adjusting for the acute phase response is essential to interpret iron status
      indicators among young Zanzibari children prone to chronic malaria and helminth
      infections.
AB  - The extent to which the acute phase response (APR) influences iron status
      indicators in chronic infections is not well documented. We investigated this
      relationship using reported recent fever and 2 acute phase proteins (APP), C
      reactive protein (CRP), and alpha-1-acid glycoprotein (AGP). In a sample of 690
      children matched on age and helminth infection status at baseline, we measured
      plasma for AGP, CRP, ferritin, transferrin receptor (TfR), and erythropoietin
      (EPO) and whole blood for hemoglobin (Hb) concentration, zinc protoporphyrin
      (ZPP), and malaria parasite density, and we obtained maternal reports of recent
      fever. We then examined the influence of the APR on each iron status indicator
      using regression analysis with Hb as the outcome variable. Ferritin was inversely
      related to Hb in the APR-unadjusted model. Adjusting for the APR using reported
      recent fever alone was not sufficient to reverse the inverse Hb-ferritin
      relationship. However, using CRP and/or AGP resulted in the expected positive
      relationship. The best fit model included reported recent fever, AGP and CRP
      (R(2) = 0.241; P < 0.001). The best fit Hb-ZPP, Hb-TfR, and Hb-EPO models
      included reported recent fever and AGP but not CRP (R(2) = 0.253, 0.310, and
      0.292, respectively; P < 0.001). ZPP, TfR, and EPO were minimally influenced by
      the APR, whereas ferritin was immensely affected. Reported recent fever alone
      cannot be used as a marker for the APR. Either AGP or CRP is useful for adjusting
      if only 1 APP can be measured. However, AGP best predicted the APR in this
      population.

PMID- 19741203
TI  - Products of the colonic microbiota mediate the effects of diet on colon cancer
      risk.
AB  - It is estimated that most colon cancers can be attributed to dietary causes. We
      have hypothesized that diet influences the health of the colonic mucosa through
      interaction with the microbiota and that it is the milieu interior that regulates
      mucosal proliferation and therefore cancer risk. To validate this further, we
      compared colonic contents from healthy 50- to 65-y-old people from populations
      with high and low risk, specifically low risk Native Africans (cancer incidence
      <1:100,000; n = 17), high risk African Americans (risk 65:100,000; n = 17), and
      Caucasian Americans (risk 50:100,000; n = 18). Americans typically consume a high
      animal protein and -fat diet, whereas Africans consume a staple diet of maize
      meal, rich in resistant starch and low in animal products. Following overnight
      fasting, rapid colonic evacuation was performed with 2 L polyethylene glycol.
      Total colonic evacuants were analyzed for SCFA, vitamins, nitrogen, and minerals.
      Total SCFA and butyrate were significantly higher in Native Africans than in both
      American groups. Colonic folate and biotin content, measured by Lactobacillus
      rhamnoses and Lactobacillus plantarum ATCC 8014 bioassay, respectively, exceeded
      normal daily dietary intakes. Compared with Africans, calcium and iron contents
      were significantly higher in Caucasian Americans and zinc content was
      significantly higher in African Americans, but nitrogen content did not differ
      among the 3 groups. In conclusion, the results support our hypothesis that the
      microbiota mediates the effect diet has on colon cancer risk by their generation
      of butyrate, folate, and biotin, molecules known to play a key role in the
      regulation of epithelial proliferation.

PMID- 19741204
TI  - Claudin 11 deficiency in mice results in loss of the Sertoli cell epithelial
      phenotype in the testis.
AB  - Tissue integrity relies on barriers formed between epithelial cells. In the
      testis, the barrier is formed at the initiation of puberty by a tight junction
      complex between adjacent Sertoli cells, thereby defining an adluminal compartment
      where meiosis and spermiogenesis occur. Claudin 11 is an obligatory protein for
      tight junction formation and barrier integrity in the testis. It is expressed by
      Sertoli cells, and spermatogenesis does not proceed beyond meiosis in its
      absence, resulting in male sterility. Sertoli cell maturation--arrest of
      proliferation and expression of proteins to support germ cell development-
      parallels tight junction assembly; however, the pathophysiology underlying the
      loss of tight junctions in the mature testis remains largely undefined. Here,
      using immunohistochemistry and microarrays we demonstrate that adult Cldn11(-/-)
      mouse Sertoli cells can proliferate while maintaining expression of mature
      markers. Sertoli cells detach from the basement membrane, acquire a fibroblast
      cell shape, are eliminated through the lumen together with apoptotic germ cells,
      and are found in epididymis. These changes are associated with tight junction
      regulation as well as actin-related and cell cycle gene expression. Thus, Cldn11(
      /-) Sertoli cells exhibit a unique phenotype whereby loss of tight junction
      integrity results in loss of the epithelial phenotype.

PMID- 19741205
TI  - Characterization and expression of the nuclear progestin receptor in zebrafish
      gonads and brain.
AB  - The zebrafish nuclear progestin receptor (nPR; official symbol PGR) was
      identified and characterized to better understand its role in regulating
      reproduction in this well-established teleost model. A full-length cDNA was
      identified that encoded a 617-amino acid residue protein with high homology to
      PGRs in other vertebrates, and contained five domains characteristic of nuclear
      steroid receptors. In contrast to the multiplicity of steroid receptors often
      found in euteleosts and attributed to probable genome duplication, only a single
      locus encoding the full-length zebrafish pgr was identified. Cytosolic proteins
      from pgr-transfected cells showed a high affinity (K(d) = 2 nM), saturable,
      single-binding site specific for a native progestin in euteleosts, 4-pregnen
      17,20 beta-diol-3-one (17,20 beta-DHP). Both 17,20 beta-DHP and progesterone were
      potent inducers of transcriptional activity in cells transiently transfected with
      pgr in a dual luciferase reporter assay, whereas androgens and estrogens had
      little potency. The pgr transcript and protein were abundant in the ovaries,
      testis, and brain and were scarce or undetectable in the intestine, muscle, and
      gills. Further analyses indicate that Pgr was expressed robustly in the preoptic
      region of the hypothalamus in the brain; proliferating spermatogonia and early
      spermatocytes in the testis; and in follicular cells and early-stage oocytes
      (stages I and II), with very low levels within maturationally competent late
      stage oocytes (IV) in the ovary. The localization of Pgr suggests that it
      mediates progestin regulation of reproductive signaling in the brain, early germ
      cell proliferation in testis, and ovarian follicular functions, but not final
      oocyte or sperm maturation.

PMID- 19741206
TI  - Pregnancy enhances sustained Ca2+ bursts and endothelial nitric oxide synthase
      activation in ovine uterine artery endothelial cells through increased connexin
      43 function.
AB  - Endothelium-mediated vasodilation is specifically enhanced in uterine circulation
      during pregnancy, and production of nitric oxide (NO) is increased in response to
      a wide array of agonists. Uterine artery endothelial cells from nonpregnant (NP
      UAECs) or pregnant (P-UAECs) ewes maintained in culture still show a pregnancy
      enhanced difference in ATP-stimulated endothelial NO synthase (eNOS; official
      symbol NOS3) activation, even though NOS3 protein, purinergic receptors, and
      associated cell signaling proteins are expressed at equal levels. We have also
      shown that the pregnancy-enhanced endothelial cell NO response to ATP requires an
      enhanced and sustained capacitative entry phase that is likely mediated via
      canonical transient receptor potential protein/inositol 1,4,5-trisphosphate
      receptor type 2 interaction. In this study, we now show by simultaneous video
      imaging of individual Fura-2-loaded cells that the pregnancy-enhanced
      capacitative entry phase is not continuous and equal in all cells, but is in fact
      mediated as a series of periodic [Ca(2+)](i) bursts within individual cells. Not
      only does pregnancy increase the number of bursts over a longer time period in
      individual cells, but also a greater proportion of cells exhibit this burst
      activity, and at high cell density this occurs in a synchronous manner. The
      mediator of cell synchronization is connexin 43 (Cx43) gap junctions because 1)
      Cx43 is readily detectable by Western blot analysis in UAECs, whereas Cx40 and
      Cx37 are weakly detected or absent, and 2) pregnancy-specific enhancement of
      [Ca(2+)](i) bursts by ATP is blocked by inhibitory loop peptides selective to
      Cx43 ((43,37)GAP27) but not by a scrambled control peptide or (40)GAP27 or
      (40,37)GAP26 peptides, which are specific to Cx40 or Cx37. The relationship
      between Ca(2+) bursts and NOS3 activation is further established by the finding
      that (43,37)GAP27 inhibits ATP-stimulated NOS3 activation but has no effect on
      cell mitogenesis. We conclude that it is pregnancy-enhanced gap junction
      communication between cells that underlies pregnancy enhancement of capacitative
      entry via TRPC3 and, in turn, NOS3 activation. Such improved gap junction
      function allows greater and more sustained [Ca(2+)](i) responses to agents such
      as ATP within a single cell, as well as the additional recruitment of greater
      numbers of cells to the response in a coordinated and synchronous manner to
      support enhanced NO production.

PMID- 19741207
TI  - Prenatal exposure of the ovine fetus to androgens reduces the proportion of
      neurons in the ventromedial and arcuate nucleus that are activated by short-term
      exposure to estrogen.
AB  - In sheep, the steroid control of gonadotropin-releasing hormone (GNRH) release is
      sexually differentiated such that estrogen can trigger a GNRH surge and attendant
      reproductive behaviors in the female, but not the male. Furthermore, female lambs
      that have been exposed to testosterone during a critical window of in utero
      development are also unable to generate a GNRH surge. This study tests the
      hypothesis that exposure of the ovine fetus to androgens alters the development
      of key steroid-receptive neuronal inputs to the GNRH neurons. In adulthood, this
      results in reduced activation of specific neurons by estrogen in the male and
      testosterone-treated female. To make this determination, groups of ewes, rams,
      and testosterone-exposed ewes were treated with estrogen, and the activation of
      neurons in the mediobasal hypothalamus and brain stem determined by
      immunocytochemistry. A lower percentage of neurons in the ventrolateral aspect of
      the ventromedial nucleus (vlVMN) and the caudal arcuate nucleus (cARC), but not
      the brainstem, was activated by a 6-h exposure to estrogen in the androgenized
      and male animals. In the vlVMN, some of these neurons contain somatostatin;
      however, the phenotype of activated neurons in the cARC remains unknown. These
      data suggest that specific neural populations in these brain regions are involved
      in the estrogen feedback control of GNRH release in the sheep, and that the
      defeminization of the surge-generating system by in utero androgen exposure
      results, in part, from a failure of estrogen to activate key neural phenotypes.

PMID- 19741208
TI  - Molecular cloning and functional characterization of a zebrafish nuclear
      progesterone receptor.
AB  - Progestagenic sex steroid hormones play critical roles in reproduction across
      vertebrates, including teleost fish. To further our understanding of how
      progesterone modulates testis functions in fish, we set out to clone a
      progesterone receptor (pgr) cDNA exhibiting nuclear hormone receptor features
      from zebrafish testis. The open reading frame of pgr consists of 1854 bp, coding
      for a 617-amino acid-long protein showing the highest similarity with other
      piscine Pgr proteins. Functional characterization of the receptor expressed in
      mammalian cells revealed that zebrafish Pgr exhibited progesterone-specific, dose
      dependent induction of reporter gene expression, with 17 alpha,20 beta-dihydroxy
      4-pregnen-3-one (DHP), a typical piscine progesterone, showing the highest
      potency. Expression of pgr mRNA: 1) appeared in embryos at 8 h after
      fertilization; 2) was significantly higher in developing ovary than in early
      transforming testis at 4 wk of age but vice versa in young adults at 12 wk of
      age, and thus resembling the expression pattern of the germ cell marker piwil1;
      and, 3) was restricted to Leydig and Sertoli cells in adult testis. Zebrafish
      testicular explants released DHP concentration dependently in response to high
      concentrations of recombinant zebrafish gonadotropins. In addition, DHP
      stimulated 11-ketotestosterone release from zebrafish testicular explants, but
      only in the presence of its immediate precursor, 11 beta-hydroxytestosterone.
      This stimulatory activity was blocked by a Pgr antagonist (RU486), suggesting
      that 11 beta-hydroxysteroid dehydrogenase activity was stimulated by DHP via Pgr.
      Our data suggest that DHP contributes to the regulation of Leydig cell
      steroidogenesis, and potentially--via Sertoli cells--also to germ cell
      differentiation in zebrafish testis.

PMID- 19741209
TI  - Reactive oxygen species mediate mitogenic growth factor signaling pathways in
      human leiomyoma smooth muscle cells.
AB  - Uterine leiomyomas are benign uterine tumors characterized by extracellular
      matrix remodeling, increased collagen deposition, and increased smooth muscle
      cell (SMC) proliferation. The reactive oxygen species (ROS) producing NADPH
      oxidase complex has been shown to be involved in the signaling pathways of
      several growth factors, cytokines, and vasoactive agents that stimulate
      proliferation of a variety of cell types. Our objective was to test the
      hypothesis that ROS derived from NADPH oxidase is a necessary component of the
      MAP kinase mitogenic pathway activated by platelet derived growth factor (PDGF)
      and epidermal growth factor (EGF) in leiomyoma SMCs (LSMCs). Primary cell
      cultures of LSMCs were used as our experimental model. Our results showed that
      stimulation of these cells with PDGF or EGF caused a marked increase in
      intracellular ROS production and that the NADPH oxidase inhibitor, DPI, blocks
      ROS production. In addition, inhibition of ROS production by NADPH oxidase
      inhibitors blocked, in a dose-dependent manner, the EGF- and PDGF-induced
      increase in [(3)H]thymidine incorporation by LSMCs. Furthermore, an exogenous
      source of ROS, hydrogen peroxide, was sufficient to stimulate [(3)H]thymidine
      incorporation in LSMCs but did not affect COL1A2 and COL3A1 mRNA levels.
      Inhibition of the NADPH oxidase complex decreased PDGF-induced MAPK1/MAPK3
      activation, whereas exogenous hydrogen peroxide induced MAPK1/MAPK3 activation.
      This article is the first report suggesting the presence of the NADPH oxidase
      system and its importance in mitogenic signaling pathways in LSMCs. The necessity
      of NADPH oxidase-derived ROS for EGF and PDGF signaling pathways leading to cell
      proliferation points to another potential therapeutic target for treatment and/or
      prevention of uterine leiomyomas.

PMID- 19741210
TI  - An iatrogenic confounding variable.

PMID- 19741211
TI  - Prospective study of Trichomonas vaginalis infection and prostate cancer
      incidence and mortality: Physicians' Health Study.
AB  - BACKGROUND: A recent nested case-control study found that the presence of
      antibodies against Trichomonas vaginalis, a common nonviral sexually transmitted
      infection, was positively associated with subsequent incidence of prostate
      cancer. We confirmed these findings in an independent population and related
      serostatus for antibodies against T vaginalis to prostate cancer incidence and
      mortality. METHODS: We conducted a case-control study nested within the
      Physicians' Health Study that included 673 case subjects with prostate cancer and
      673 individually matched control subjects who had available plasma samples.
      Plasma from blood samples collected at baseline was assayed for antibodies
      against T vaginalis with an enzyme-linked immunosorbent assay. We used
      conditional logistic regression to estimate the odds ratios (ORs) of incident
      prostate cancer, extraprostatic prostate cancer, and cancer that would ultimately
      progress to bony metastases or prostate cancer-specific death. RESULTS: Although
      not statistically significant, the magnitude of the association between T
      vaginalis-seropositive status and overall prostate cancer risk (OR = 1.23, 95%
      confidence interval [CI] = 0.94 to 1.61) was similar to that reported previously.
      Furthermore, a seropositive status was associated with statistically
      significantly increased risks of extraprostatic prostate cancer (OR = 2.17, 95%
      CI = 1.08 to 4.37) and of cancer that would ultimately progress to bony
      metastases or prostate cancer-specific death (OR = 2.69, 95% CI = 1.37 to 5.28).
      CONCLUSIONS: This large prospective case-control study obtained further support
      for an association between a seropositive status for antibodies against T
      vaginalis and the risk of prostate cancer, with statistically significant
      associations identified for the risk of extraprostatic prostate cancer and for
      clinically relevant, potentially lethal prostate cancer.

PMID- 19741212
TI  - Isn't amyloid more than just a marker for Alzheimer disease?

PMID- 19741213
TI  - Another gene for ALS: mutations in sporadic cases and the rare variant
      hypothesis.

PMID- 19741214
TI  - Doctoring 2009: embracing the challenge.

PMID- 19741215
TI  - Analysis of FUS gene mutation in familial amyotrophic lateral sclerosis within an
      Italian cohort.
AB  - OBJECTIVE: Mutations in the FUS gene on chromosome 16 have been recently
      discovered as a cause of familial amyotrophic lateral sclerosis (FALS). This
      study determined the frequency and identities of FUS gene mutations in a cohort
      of Italian patients with FALS. METHODS: We screened all 15 coding exons of FUS
      for mutations in 94 Italian patients with FALS. RESULTS: We identified 4 distinct
      missense mutations in 5 patients; 2 were novel. The mutations were not present in
      376 healthy Italian controls and thus are likely to be pathogenic. CONCLUSIONS:
      Our results demonstrate that FUS mutations cause approximately 4% of familial
      amyotrophic lateral sclerosis cases in the Italian population.

PMID- 19741216
TI  - Mutations in FUS cause FALS and SALS in French and French Canadian populations.
AB  - BACKGROUND: The identification of mutations in the TARDBP and more recently the
      identification of mutations in the FUS gene as the cause of amyotrophic lateral
      sclerosis (ALS) is providing the field with new insight about the mechanisms
      involved in this severe neurodegenerative disease. METHODS: To extend these
      recent genetic reports, we screened the entire gene in a cohort of 200 patients
      with ALS. An additional 285 patients with sporadic ALS were screened for variants
      in exon 15 for which mutations were previously reported. RESULTS: In total, 3
      different mutations were identified in 4 different patients, including 1 3-bp
      deletion in exon 3 of a patient with sporadic ALS and 2 missense mutations in
      exon 15 of 1 patient with familial ALS and 2 patients with sporadic ALS.
      CONCLUSIONS: Our study identified sporadic patients with mutations in the FUS
      gene. The accumulation and description of different genes and mutations helps to
      develop a more comprehensive picture of the genetic events underlying amyotrophic
      lateral sclerosis.

PMID- 19741217
TI  - Database duels do not advance quality improvement.

PMID- 19741218
TI  - The Open School: a framework for innovation.

PMID- 19741219
TI  - British lessons on health care reform.

PMID- 19741220
TI  - Getting past denial--the high cost of health care in the United States.

PMID- 19741221
TI  - Health care reform and clinical culture.

PMID- 19741222
TI  - The tragedy of the commons revisited.

PMID- 19741223
TI  - Fiscal responsibility and health care reform.

PMID- 19741224
TI  - Setbacks and fissions--reconsidering the scope and timing of reform.

PMID- 19741225
TI  - Images in clinical medicine. De Garengeot's hernia.

PMID- 19741226
TI  - Reemergence of PML in natalizumab-treated patients--new cases, same concerns.

PMID- 19741228
TI  - Treatment of progressive multifocal leukoencephalopathy associated with
      natalizumab.
AB  - We describe the clinical and therapeutic course of a 52-year-old patient with
      multiple sclerosis in whom progressive multifocal leukoencephalopathy (PML)
      developed after 12 months of therapy with natalizumab. The patient was
      hospitalized 2 months after the onset of neurologic and psychiatric symptoms and
      was treated with plasma exchange and immunoadsorption to eliminate natalizumab.
      After a brief improvement, he became critically ill with an apparent episode of
      immune reconstitution inflammatory syndrome. Steroid-pulse therapy led to
      stabilization of the patient's condition and clinically significant recovery.
      This case illustrates that prompt diagnosis and treatment may improve the outcome
      in patients with severe PML associated with natalizumab therapy.

PMID- 19741227
TI  - Asymptomatic reactivation of JC virus in patients treated with natalizumab.
AB  - BACKGROUND: Progressive multifocal leukoencephalopathy (PML) occurs in a fraction
      of patients with multiple sclerosis who were treated with natalizumab. Most
      adults who are infected with the JC virus, the etiologic agent in PML, do not
      have symptoms. We sought to determine whether exposure to natalizumab causes
      subclinical reactivation and neurotropic transformation of JC virus. METHODS: We
      followed 19 consecutive patients with multiple sclerosis who were treated with
      natalizumab over an 18-month period, performing quantitative polymerase-chain
      reaction assays in blood and urine for JC virus reactivation; BK virus, a JC
      virus-related polyomavirus, was used as a control. We determined JC virus
      specific T-cell responses by means of an enzyme-linked immunospot assay and
      antibody responses by means of an enzyme-linked immunosorbent assay and analyzed
      JC virus regulatory-region sequences. RESULTS: After 12 months of natalizumab
      therapy, the prevalence of JC virus in the urine of the 19 patients increased
      from a baseline value of 19% to 63% (P=0.02). After 18 months of treatment, JC
      virus was detectable in 3 of 15 available plasma samples (20%) and in 9 of 15
      available samples of peripheral-blood mononuclear cells (60%) (P=0.02). JC virus
      regulatory-region sequences in blood samples and in most of the urine samples
      were similar to those usually found in PML. Conversely, BK virus remained stable
      in urine and was undetectable in blood. The JC virus-specific cellular immune
      response dropped significantly between 6 and 12 months of treatment, and
      variations in the cellular immune response over time tended to be greater in
      patients in whom JC viremia developed. None of the patients had clinical or
      radiologic signs of PML. CONCLUSIONS: Subclinical reactivation of JC virus occurs
      frequently in natalizumab-treated patients with multiple sclerosis. Viral
      shedding is associated with a transient drop in the JC virus-specific cellular
      immune response.

PMID- 19741229
TI  - Progressive multifocal leukoencephalopathy after natalizumab monotherapy.
AB  - We describe progressive multifocal leukoencephalopathy (PML) caused by infection
      with human polyomavirus JC virus in a patient with multiple sclerosis who was
      treated with natalizumab. The first PML symptoms appeared after 14 monthly
      infusions of the drug. Magnetic resonance imaging (MRI) showed a presumed
      multiple sclerosis lesion, and JC virus DNA was not detected on polymerase-chain
      reaction (PCR) assay of cerebrospinal fluid. The patient's symptoms worsened, and
      the diagnosis of PML was established with a more sensitive quantitative PCR assay
      after 16 infusions of natalizumab. Plasma exchange was used to accelerate
      clearance of natalizumab. Approximately 3 weeks after plasma exchange, an immune
      reconstitution inflammatory syndrome appeared. JC virus DNA was no longer
      detectable on quantitative PCR assay, and the patient's symptoms improved.

PMID- 19741231
TI  - Images in clinical medicine. Baker's cyst in a patient with rheumatoid arthritis.

PMID- 19741230
TI  - Parenteral nutrition in the critically ill patient.

PMID- 19741232
TI  - Case records of the Massachusetts General Hospital. Case 28-2009. A 68-year-old
      man with fatigue, cough, and peripheral-blood monocytosis.

PMID- 19741234
TI  - Understanding abdominal aortic aneurysm.

PMID- 19741235
TI  - Mutation in TET2 in myeloid cancers.

PMID- 19741236
TI  - Autologous stem-cell transplantation for multiple myeloma.

PMID- 19741237
TI  - Age, neuropathology, and dementia.

PMID- 19741238
TI  - Medical end-of-life practices under the euthanasia law in Belgium.

PMID- 19741239
TI  - Ruptured abdominal aortic aneurysm related to IgG4 periaortitis.

PMID- 19741240
TI  - Puerto Rican women's perceptions of heart disease risk.
AB  - Women frequently fail to recognize that coronary heart disease (CHD), not breast
      cancer, is the primary cause of female mortality. CHD mortality among U.S.
      mainland Puerto Rican (PR) women is second only to African American women. It is
      unknown what PR women understand about their risk, what factors they believe
      contribute to CHD, or whether they know the atypical symptoms often experienced
      by women. Most CHD studies exclude Hispanic women. Those that do often aggregate
      their results, making subgroup variations invisible. This study explored
      awareness of CHD symptoms, risks, and help-seeking behaviors among 12 PR women.
      Focus group methodology revealed that participants were unaware of their risk and
      had misconceptions about CHD symptoms and contributing factors. Barriers to early
      recognition and treatment included lack of knowledge, gender role conflict
      (caregiver vs. care recipient), and fears of falsely alarming family members or
      the embarrassment of feeling "dismissed" by health care providers.

PMID- 19741241
TI  - Fourier domain optical coherence tomography as a noninvasive means for in vivo
      detection of retinal degeneration in Xenopus laevis tadpoles.
AB  - PURPOSE: To determine the efficacy of Fourier domain optical coherence tomography
      (FD-OCT) as a noninvasive, nonlethal method for detecting in vivo, pathologic
      signs of retinal degeneration in Xenopus laevis larvae. METHODS: A prototype OCT
      system using FD detection customized for tadpole imaging was used to
      noninvasively obtain retinal scans in two different transgenic X. laevis models
      of retinal degeneration. FD-OCT retinal scans were compared with laser scanning
      confocal micrographs of histologic sections of the same eye. Retinal thickness
      was measured in the histologic micrographs and compared with in vivo measurements
      acquired with FD-OCT. RESULTS: In vivo retinal images of X. laevis tadpoles were
      obtained that visualized the major retinal layers. FD-OCT successfully detected
      the ablation of rod outer segments (OS) in degenerating tadpole eyes.
      Measurements from FD-OCT and histology showed a decrease in retinal thickness in
      transgenic mutant tadpoles relative to the wild-type control. The accumulation of
      phagosomes from dying rod OS was also visualized in the retinal pigment
      epithelium (RPE) in a degenerating tadpole retina. CONCLUSIONS: This report
      demonstrates that FD-OCT is a viable technique for screening, diagnosing, and
      monitoring retinal degeneration in X. laevis tadpoles in vivo.

PMID- 19741242
TI  - Developmental corneal innervation: interactions between nerves and specialized
      apical corneal epithelial cells.
AB  - PURPOSE: The corneal epithelium is one of the most highly innervated structures
      in the body, and proper innervation is necessary for corneal maintenance and
      sensation. However, little is known about how these nerves function and how
      innervation occurs developmentally. The authors have examined certain aspects of
      corneal innervation in the developing chicken embryo. METHODS: DiI was used to
      determine the source of the neurons responsible for innervating the cornea.
      Immunohistochemistry, electron microscopy, and immunoelectron microscopy were
      used to examine corneal innervation and the relationships that develop between
      nerves and corneal epithelial cells. RESULTS: Corneal nerves in the embryonic
      chicken originate entirely from the ophthalmic lobe of the trigeminal ganglion.
      Within the cornea the nerves interact with apical corneal epithelial (ACE) cells
      to form specialized structures that are synapse-like because they contain
      accumulations of vesicles and have the SV2 synaptic vesicle protein. These ACE
      cells themselves have unique characteristics, including transient expression of
      the neuronal isoform of class III beta-tubulin and formation of extensive
      intercellular channels and clefts that contain these specialized synapse-like
      structures and nerves; in addition, they are mitotically active. Given that these
      ACE cells react with a monoclonal antibody against this neuronal isoform of beta
      tubulin (the TuJ-1 antibody), we have termed them TuJ-1(+)ACE cells. CONCLUSIONS:
      During avian corneal development the nerves make close associations with a
      specialized type of ACE cell. There they form synapse-like structures, suggesting
      that not all nerves within the CE terminate as free nerve endings.

PMID- 19741243
TI  - Silencing of the CHM gene alters phagocytic and secretory pathways in the retinal
      pigment epithelium.
AB  - PURPOSE: Choroideremia (CHM) is an X-linked progressive degeneration of the
      retinal pigment epithelium (RPE), photoreceptors, and choroid caused by mutations
      in the CHM gene, which encodes Rab escort-protein-1 (REP-1). REP-1 enables
      posttranslational isoprenyl modification of Rab GTPases, proteins that control
      vesicle formation, movement, docking, and fusion. The aim of this study was to
      determine the effect of REP-1 depletion on vesicular trafficking in phagocytic
      and secretory pathways of human RPE. METHODS: In vitro, REP-1 expression was
      inhibited in human fetal RPE (hfRPE) cells by siRNA knockdown and its effects
      measured on the uptake of bovine photoreceptor outer segments (POS), proteolysis
      of POS rhodopsin, phagosomal pH, phagosome fusion with early and late
      endosomes/lysosomes, and polarized secretion of cytokines. RESULTS: Depletion of
      REP-1 in human RPE cells did not affect POS internalization but reduced
      phagosomal acidification and delayed POS protein clearance. REP-1 depletion also
      caused a decrease in the association of POS-containing phagosomes with late
      endosomal markers (Rab7, LAMP-1) and increases in the secretion of monocyte
      chemotactic protein (MCP-1) and interleukin (IL)-8 by hfRPE cells. CONCLUSIONS:
      Lack of REP-1 protein expression in hfRPE cells leads to reduced degradation of
      POS most likely because of the inhibition of phagosome-lysosome fusion events and
      increased constitutive secretion of MCP-1 and IL-8. These observations may
      explain the accumulation of unprocessed outer segments within the phagolysosomes
      of RPE cells and the presence of inflammatory cells in the choroid of patients
      with CHM.

PMID- 19741244
TI  - Effect of HCN channel inhibition on retinal morphology and function in normal and
      dystrophic rodents.
AB  - PURPOSE: To elucidate short- and long-term effects of ivabradine, an inhibitor of
      the hyperpolarization-activated current (I(f)) recently approved for treatment of
      stable angina, on retinal function and integrity. As careful ivabradine
      administration is recommended for patients with retinitis pigmentosa, an
      additional objective was to test the consequences of repeated ivabradine delivery
      on retinal integrity in the rd10 mouse, an animal model of the human degenerative
      disease. METHODS: The electroretinogram (ERG) was recorded in intact anesthetized
      animals in response to flashes or time-varied sinusoidal light stimuli of
      different frequency. Retinal integrity and hyperpolarization-activated cyclic
      nucleotide-gated (HCN) channel distribution were assessed by immunocytochemistry,
      confocal microscopy, and Western blot analysis. RESULTS: Neither a- nor b-waves
      of the flash-ERG were significantly affected by ivabradine administration.
      Conversely, reversible changes in the response to sinusoidal stimuli were
      observed during both acute and continued treatment. HCN inhibition enhanced the
      gain of frequency-response curves (FRCs) at the lowest stimulus frequencies and
      reduced it in the 1- to 7-Hz range. These effects were dose dependent and
      reverted to normal 1 week after discontinuation of ivabradine. Retinal morphology
      and distribution of HCN were preserved and no signs of retinal damage were
      observed in healthy animals. HCN inhibition in dystrophic mice had no effect on
      either extent or progression of retinal degeneration. CONCLUSIONS: The results
      are consistent with the hypothesis that the visual symptoms reported by patients
      during prolonged treatment with ivabradine are due only to a reversible
      pharmacologic effect.

PMID- 19741245
TI  - Impaired angiogenic response in the corneas of mice lacking osteopontin.
AB  - PURPOSE: To investigate the effects of loss of osteopontin (OPN) in the
      development of neovascularization in corneal stroma in mice. Cell culture study
      was also conducted to clarify the effects of OPN in transforming growth factor
      (TGF) beta1-driven cell signaling and expression of vascular endothelial growth
      factor (VEGF). METHODS: Ocular fibroblasts from wild-type and OPN-null mice were
      used to study the role of OPN in TGFbeta1 signal and VEGF expression. The effect
      of the absence of OPN on corneal neovascularization was evaluated in mice.
      RESULTS: In ocular fibroblast culture, loss of OPN attenuated TGFbeta1 signals
      (Smad3 and p38) and reduced expression of VEGF. Loss of OPN attenuated
      neovascularization in corneal stroma in mice. CONCLUSIONS: OPN is involved in
      VEGF expression in cultured fibroblasts and is required for neovascularization in
      corneal stroma in vivo.

PMID- 19741246
TI  - Increased 24-hour variation of human intraocular pressure with short axial
      length.
AB  - PURPOSE: To characterize 24-hour variation of intraocular pressure (IOP) in
      healthy young adults based on the axial length of the eye. METHODS: Twenty-four
      hour IOP data were collected from nine healthy young adults with hyperopia, age
      range 18 to 25 years, in a sleep laboratory. Every 2 hours, measurements of IOP
      were taken in the participants after 5 minutes in the supine position and 5
      minutes in the sitting position during the 16-hour diurnal/wake period as well
      when supine in bed during the 8-hour nocturnal/sleep period. Variations in 24
      hour IOP in this hyperopia group were analyzed, together with previously
      collected data under the same laboratory conditions from 32 age-matched subjects
      with emmetropia or mild myopia (emmetropia group) and 34 subjects with moderate
      to severe myopia (myopia group). RESULTS: Average diurnal sitting IOP was lower
      in the hyperopia group than in the other two groups. The difference between the
      diurnal sitting and diurnal supine IOP was larger in the hyperopia group than in
      the myopia group. In all three groups, the nocturnal supine IOP was higher than
      the diurnal sitting IOP. This elevation in habitual IOP was most significant in
      the hyperopia group. The hyperopia group also presented a significant IOP
      elevation within the nocturnal period. Simulated 24-hour rhythms of supine IOP
      were detected in all groups with different phase timings, but simulated 24-hour
      IOP variations were not different. The 24-hour habitual IOP fluctuation (peak
      minus trough) was inversely correlated to axial length. CONCLUSIONS: Shorter eyes
      had a larger 24-hour IOP variation than longer eyes in healthy young adults.

PMID- 19741247
TI  - Severe retinal degeneration caused by a novel rhodopsin mutation.
AB  - PURPOSE: To identify a new mouse mutation developing early-onset dominant retinal
      degeneration, to determine the causative gene mutation, and to investigate the
      underlying mechanism. METHODS: Retinal phenotype was examined by indirect
      ophthalmoscopy, histology, transmission electron microscopy,
      immunohistochemistry, Western blot analysis, and electroretinography. Causative
      gene mutation was determined by genomewide linkage analysis and DNA sequencing.
      Structural modeling was used to predict the impact of the mutation on protein
      structure. RESULTS: An ENU-mutagenized mouse line (R3), displaying attenuated
      retinal vessels and pigmented patches, was identified by fundus examination.
      Homozygous R3/R3 mice lost photoreceptors rapidly, leaving only a single row of
      photoreceptor nuclei at postnatal day 18. The a- and b-waves of ERG were flat in
      R3/R3 mice, whereas heterozygous R3/+ mice showed reduced amplitude of a- and b
      waves. The R3/+ mice had a slower rate of photoreceptor cell loss than compound
      heterozygous R3/- mice with a null mutant allele. The R3 mutation was mapped and
      verified to be a rhodopsin point mutation, a c.553T>C for a p.C185R substitution.
      The side chain of Arg(185) impacted on the extracellular loop of the protein.
      Mutant rhodopsin-C185R protein accumulated in the photoreceptor inner segments,
      cellular bodies, or both. CONCLUSIONS: Rhodopsin C185R mutation leads to severe
      retinal degeneration in R3 mutant mice. A dosage-dependent accumulation of
      misfolded mutant proteins likely triggers or stimulates the death of rod
      photoreceptors. The presence of a wild-type rhodopsin allele can delay the loss
      of photoreceptor cells in R3/+ mice.

PMID- 19741248
TI  - Spatiotemporal interactions in retinal prosthesis subjects.
AB  - PURPOSE: Vision loss due to retinitis pigmentosa affects an estimated 15 million
      people worldwide. Through collaboration between Second Sight Medical Products,
      Inc., and the Doheny Eye Institute, six blind human subjects underwent
      implantation with epiretinal 4 x 4 electrode arrays designed to directly
      stimulate the remaining cells of the retina, with the goal of restoring
      functional vision by applying spatiotemporal patterns of stimulation. To better
      understand spatiotemporal interactions between electrodes during synchronous and
      asynchronous stimulation, the authors investigated how percepts changed as a
      function of pulse timing across the electrodes. METHODS: Pulse trains (20, 40,
      80, and 160 Hz) were presented on groups of electrodes with 800, 1600, or 2400
      microm center-to-center separation. Stimulation was either synchronous (pulses
      were presented simultaneously across electrodes) or asynchronous (pulses were
      phase shifted). Using a same-different discrimination task, the authors were able
      to evaluate how the perceptual quality of the stimuli changed as a function of
      phase shifts across multiple electrodes. RESULTS: Even after controlling for
      electric field interactions, subjects could discriminate between spatiotemporal
      pulse train patterns based on differences of phase across electrodes as small as
      3 ms. These findings suggest that the quality of the percept is affected not only
      by electric field interactions but also by spatiotemporal interactions at the
      neural level. CONCLUSIONS: During multielectrode stimulation, interactions
      between electrodes have a significant influence on the quality of the percept.
      Understanding how these spatiotemporal interactions at the neural level influence
      percepts during multielectrode stimulation is fundamental to the successful
      design of a retinal prosthesis.

PMID- 19741250
TI  - Impairments of contrast discrimination and contrast adaptation in glaucoma.
AB  - PURPOSE: Contrast detection is commonly measured clinically; however,
      discrimination between contrasts is also important for natural vision.
      Furthermore, optimal performance requires the visual system to adapt to ambient
      contrast conditions. Recent studies of primate neurophysiology demonstrate
      significant retinal involvement in contrast adaptation. This study was conducted
      to investigate whether glaucoma alters contrast adaptation. Both detection and
      discrimination task performance were examined. METHODS: Psychophysical contrast
      detection and discrimination thresholds were measured in central vision, for a
      vertically oriented D6 centered on 3 cyc/deg. Thresholds were measured with and
      without adaptation to low (15%)- and high (70%)-contrast, vertically oriented, 3
      cyc/deg sinusoidal gratings. Fifteen people with glaucoma, and 15 age-similar
      control subjects participated. Full-contrast discrimination (dipper) functions
      were measured for a subset (three patients with glaucoma and three control
      subjects). RESULTS: On average, the glaucoma group showed elevated detection and
      discrimination thresholds relative to control subjects (detection: t(28) = 2.42;
      P = 0.02; discrimination: F(1,28) = 6.157, P = 0.02). For the subset of
      additionally tested participants, normalized contrast discrimination functions
      were similarly shaped for all observers. Glaucoma group thresholds were less
      influenced by contrast adaptation than were control subjects, for discrimination
      (F(1,28) = 10.89, P < 0.01) but not detection (F(1,28) = 2.28; P = 0.11).
      Differences between groups were greatest for low-contrast stimuli (significant
      interaction between contrast and group: P < 0.01). CONCLUSIONS: Glaucoma alters
      the effect of contrast adaptation on discrimination performance, particularly at
      low contrast. The study of suprathreshold aspects of vision may reveal new
      insights into the pathophysiology of glaucoma and possibly relate better to real
      world visual performance than detection measures.

PMID- 19741249
TI  - Hemoglobin expression and regulation in glaucoma: insights into retinal ganglion
      cell oxygenation.
AB  - PURPOSE: To determine expression, cellular distribution, and regulation of
      hemoglobin (Hb) in normal and glaucomatous tissues. METHODS: Proteomic analysis
      of Hb expression was conducted on protein samples from ocular hypertensive and
      control rat eyes and human donor eyes with or without glaucoma. Proteomic
      findings were validated by quantitative (q)RT-PCR, Western blot analysis,
      immunohistochemistry, and the analysis of new Hb synthesis in culture. Hypoxic
      regulation of Hb expression was also studied in primary cultures of rat RGCs and
      macroglia and after transfer of the glia-conditioned medium to RGCs. The role of
      erythropoietin (EPO) signaling in Hb induction and cell survival was determined
      by applying recombinant (r)EPO treatment and performing EPO neutralization
      experiments by using soluble EPO receptor treatment of hypoxic cultures. RESULTS:
      In vivo findings revealed Hb expression in the retina and optic nerve head
      macroglia and RGCs, suggesting an approximately two-fold upregulation in ocular
      hypertensive rat eyes and glaucomatous human donor eyes relative to the control
      eyes. In vitro findings collectively supported that hypoxia boosts glial Hb
      expression through hypoxia-inducible EPO signaling in an autocrine manner. Based
      on passive transfer experiments, hypoxia-induced production of glial EPO was also
      found to upregulate Hb expression in RGCs in a paracrine manner, thereby
      increasing the hypoxic survival of these neurons. CONCLUSIONS: Findings of this
      study provide new insights into tissue oxygen transport in the inner retina and
      optic nerve head through the regulated expression of Hb in macroglia and RGCs.
      Upregulation of Hb expression appears to be an intrinsic protective mechanism to
      facilitate cellular oxygenation and may also provide free radical scavenging.

PMID- 19741251
TI  - Functional role of thymic stromal lymphopoietin in chronic allergic
      keratoconjunctivitis.
AB  - PURPOSE: Previous reports have shown that thymic stromal lymphopoietin (TSLP)
      plays a role in atopic diseases. This study was undertaken to investigate the
      expression of TSLP in the giant papillae obtained from patients with vernal
      keratoconjunctivitis (VKC) or atopic keratoconjunctivitis (AKC), and its
      functional roles were analyzed. METHODS: TSLP mRNA expression was examined in
      resected conjunctival samples obtained from four patients with VKC/AKC and three
      control subjects by reverse transcription-polymerase chain reaction. Anti-TSLP,
      anti-dendritic cell-limbic system-associated membrane protein (anti-DC-LAMP), and
      anti-tryptase immunohistochemical staining was performed with 10 resected giant
      papillae. Human conjunctival epithelial (HCJE) cells were stimulated with poly
      I:C, with and without endosomal inhibitor, to examine TSLP mRNA expression.
      Cultured human mast cells were stimulated with recombinant (r)TSLP to analyze the
      downstream effect of TSLP. RESULTS: All four VKC/AKC samples showed TSLP mRNA
      expression; however, no TSLP mRNA expression was found in the control
      conjunctivae. Anti-TSLP immunohistochemical staining showed preferential
      expression in the epithelial cells and some infiltrated cells of the giant
      papillae, but not in the control conjunctivae. Double immunohistochemical
      staining with TSLP and DC-LAMP or tryptase showed the existence of activated
      dendritic cells and mast cells near TSLP-positive cells in the giant papillae.
      Real-time PCR analysis showed that poly I:C induced TSLP mRNA expression in HCJEs
      in an endosomal-function-dependent manner and that rTSLP could induce IL-13 mRNA
      expression in the mast cells synergistically with IL-33. CONCLUSIONS: The TSLP
      protein produced in conjunctival epithelial cells plays a role in severe ocular
      allergy through the activation of dendritic cells and mast cells in synergy with
      other cytokines.

PMID- 19741252
TI  - In vitro and in vivo protein-bound tyrosine nitration characterized by diagonal
      chromatography.
AB  - A new proteomics technique for analyzing 3-nitrotyrosine-containing peptides is
      presented here. This technique is based on the combined fractional diagonal
      chromatography peptide isolation procedures by which specific classes of peptides
      are isolated following a series of identical reverse-phase HPLC separation steps.
      Here dithionite is used to reduce 3-nitrotyrosine to 3-aminotyrosine peptides,
      which thereby become more hydrophilic. Our combined fractional diagonal
      chromatography technique was first applied to characterize tyrosine nitration in
      tetranitromethane-modified BSA and further led to a high quality list of 335
      tyrosine nitration sites in 267 proteins in a peroxynitrite-treated lysate of
      human Jurkat cells. We then analyzed a serum sample of a C57BL6/J mouse in which
      septic shock was induced by intravenous Salmonella infection and identified six
      in vivo nitration events in four serum proteins, thereby illustrating that our
      technique is sufficiently sensitive to identify rare in vivo tyrosine nitration
      sites in a very complex background.

PMID- 19741253
TI  - The cAMP capture compound mass spectrometry as a novel tool for targeting cAMP
      binding proteins: from protein kinase A to potassium/sodium hyperpolarization
      activated cyclic nucleotide-gated channels.
AB  - The profiling of subproteomes from complex mixtures on the basis of small
      molecule interactions shared by members of protein families or small molecule
      interaction domains present in a subset of proteins is an increasingly important
      approach in functional proteomics. Capture Compound Mass Spectrometry (CCMS) is a
      novel technology to address this issue. CCs are trifunctional molecules that
      accomplish the reversible binding of target protein families to a selectivity
      group (small molecule), covalent capturing of the bound proteins by
      photoactivated cross-linking through a reactivity group, and pullout of the small
      molecule-protein complexes through a sorting function, e.g. biotin. Here we
      present the design, synthesis, and application of a new Capture Compound to
      target and identify cAMP-binding proteins in complex protein mixtures. Starting
      with modest amounts of total protein mixture (65-500 microg), we demonstrate that
      the cAMP-CCs can be used to isolate bona fide cAMP-binding proteins from lysates
      of Escherichia coli, mammalian HepG2 cells, and subcellular fractions of
      mammalian brain, respectively. The identified proteins captured by the cAMP-CCs
      range from soluble cAMP-binding proteins, such as the catabolite gene activator
      protein from E. coli and regulatory subunits of protein kinase A from mammalian
      systems, to cAMP-activated potassium/sodium hyperpolarization-activated cyclic
      nucleotide-gated channels from neuronal membranes and specifically synaptosomal
      fractions from rat brain. The latter group of proteins has never been identified
      before in any small molecule protein interaction and mass spectrometry-based
      proteomics study. Given the modest amount of protein input required, we expect
      that CCMS using the cAMP-CCs provides a unique tool for profiling cAMP-binding
      proteins from proteome samples of limited abundance, such as tissue biopsies.

PMID- 19741254
TI  - The role of calcium-independent phospholipase A2 in cardiolipin remodeling in the
      spontaneously hypertensive heart failure rat heart.
AB  - Cardiolipin (CL) is an essential phospholipid component of the inner
      mitochondrial membrane. In the mammalian heart, the functional form of CL is
      tetralinoleoyl CL [(18:2)(4)CL]. A decrease in (18:2)(4)CL content, which is
      believed to negatively impact mitochondrial energetics, occurs in heart failure
      (HF) and other mitochondrial diseases. Presumably, (18:2)(4)CL is generated by
      remodeling nascent CL in a series of deacylation-reacylation cycles; however, our
      overall understanding of CL remodeling is not yet complete. Herein, we present a
      novel cell culture method for investigating CL remodeling in myocytes isolated
      from Spontaneously Hypertensive HF rat hearts. Further, we use this method to
      examine the role of calcium-independent phospholipase A(2) (iPLA(2)) in CL
      remodeling in both HF and nonHF cardiomyocytes. Our results show that 18:2
      incorporation into (18:2)(4)CL is: a) performed singly with respect to each fatty
      acyl moiety, b) attenuated in HF relative to nonHF, and c) partially sensitive to
      iPLA(2) inhibition by bromoenol lactone. These results suggest that CL remodeling
      occurs in a step-wise manner, that compromised 18:2 incorporation contributes to
      a reduction in (18:2)(4)CL in the failing rat heart, and that mitochondrial
      iPLA(2) plays a role in the remodeling of CL's acyl composition.

PMID- 19741255
TI  - Clinical year in review I: Interstitial lung disease, pulmonary vascular disease,
      pulmonary infections, and cardiopulmonary exercise testing and pulmonary
      rehabilitation.

PMID- 19741256
TI  - Clinical year in review II: Sepsis, mechanical ventilation, occupational and
      environmental lung disease, and sleep.

PMID- 19741257
TI  - Clinical year in review III: Chronic obstructive pulmonary disease, treatment of
      tobacco dependence, lung cancer, and lung transplantation.

PMID- 19741258
TI  - Clinical year in review IV: Pediatric pulmonary and critical care, cystic
      fibrosis, asthma, and pleural disease.

PMID- 19741260
TI  - Chronic obstructive pulmonary disease: reactive past, preventive future.

PMID- 19741259
TI  - Developmental aspects of the upper airway: report from an NHLBI Workshop, March 5
      6, 2009.
AB  - The upper airway serves three important functions: respiration, swallowing, and
      speech. During development it undergoes significant structural and functional
      changes that affect its size, shape, and mechanical properties. Abnormalities of
      the upper airway require prompt attention, because these often alter ventilatory
      patterns and gas exchange, particularly during sleep when upper airway motor tone
      and ventilatory drive are diminished. Recognizing the relationship of early life
      events to lung health and disease, the National Heart, Lung, and Blood Institute
      (NHLBI), with cofunding from the Office of Rare Diseases (ORD), convened a
      workshop of extramural experts, from many disciplines. The objective of the
      workshop was: (1) to review the state of science in pediatric upper airway
      disorders; (2) to make recommendations to the Institute to fill knowledge gaps;
      (3) to prioritize new research directions; and (4) to capitalize on scientific
      opportunities. This report provides recommendations that could facilitate
      translation of basic research findings into practice to better diagnose, treat,
      and prevent airway compromise in children.

PMID- 19741261
TI  - Burden and pathogenesis of chronic obstructive pulmonary disease.
AB  - The burden of chronic obstructive pulmonary disease (COPD) is rising, incurring a
      major health care burden worldwide. There is no specific therapy other than
      smoking cessation, which is only partially successful. The condition is
      recognized to be the result of abnormal control of the inflammatory response to
      known risk factors, although the exact mechanisms have yet to be identified.
      However alpha(1)-antitrypsin deficiency represents a human model of all the
      components of COPD (especially emphysema), and the genetic nature allows family
      studies of subjects who are well or in the early stages of disease progression.
      Emphysema distribution has facilitated further understanding of physiologic
      impairment with particular reference to discordance between FEV(1) and tests of
      gas transfer. The condition also emphasizes the role of the neutrophil in the
      inflammatory cascade in both deficiency and usual COPD. Deregulation and
      resistance of the inflammatory cytokine cascade appears to be a regular feature
      of usual COPD, and may represent a premature ageing phenotype. Molecular studies
      provide new insights that may lead to specific therapies to halt progression.

PMID- 19741262
TI  - New paradigms in the pathogenesis of chronic obstructive pulmonary disease I.
AB  - This paper reviews the potential participation of novel pathogenic mechanisms in
      chronic obstructive pulmonary disease (COPD) relating to aging, including
      oxidative stress and enhanced expression of markers of senescence in
      emphysematous lungs and the potential enhanced tissue destruction involving
      alveolar apoptosis. These insights provide new beginnings for future
      investigations in the pathobiology of COPD which may lead to future therapies for
      this condition.

PMID- 19741263
TI  - New paradigms in the pathogenesis of chronic obstructive pulmonary disease II.
AB  - A vicious circle of infection and inflammation in the airways in chronic
      obstructive pulmonary disease (COPD) could cause progressive lung damage and
      contribute to progressive loss of lung function characteristic of this disease.
      Bacteria and viruses cause a substantial proportion of exacerbations of COPD,
      which have now been clearly characterized as inflammatory events with adverse
      consequences in the course of COPD. Chronic infection by virus, bacteria, and
      other microbes is also prevalent in COPD, and human and experimental data are
      linking this chronic infection to COPD pathogenesis. COPD is heterogeneous;
      therefore it is likely infections have a varying degree of importance among
      patients with this disease.

PMID- 19741264
TI  - Chronic obstructive pulmonary disease in men and women: myths and reality.
AB  - Chronic diseases have a variable impact on men and women due to the complex
      interaction between biological sex and environmental risk factors to which men
      and women are differentially exposed. Sex differences have not been adequately
      explored in chronic obstructive pulmonary disease (COPD), as most studies have
      either had small sample sizes or not enough women to allow for accurate
      comparisons. This article will address sex differences in susceptibility,
      expression of COPD subtypes, and activity-related breathlessness, and will
      identify key areas for further investigation.

PMID- 19741265
TI  - Genetics and genomics of chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) fulfills criteria for a complex
      genetic disease in which environmental factors interact with multiple polymorphic
      genes to influence susceptibility. Finding the genes that influence
      susceptibility can be approached in hypothesis testing or unbiased study designs.
      In candidate gene association studies, genetic variation in, and/or levels of,
      expression of genes known or suspected to be involved in the pathogenesis of COPD
      are compared in affected and unaffected individuals. Although this approach is
      useful it is limited by our present knowledge of disease pathophysiology.
      Genomewide studies of gene expression and of genetic variation are now possible
      and are not constrained by our limited knowledge. Although both of these unbiased
      approaches are in their infancy, they have already provided exciting new avenues
      for future investigation and potentially now approaches to risk prediction and
      therapy.

PMID- 19741266
TI  - Biomarkers in chronic obstructive pulmonary disease.
AB  - Currently, with exception of lung function tests, there are no well validated
      biomarkers or surrogate endpoints that can be used to establish efficacy of novel
      drugs for chronic obstructive pulmonary disease (COPD). However, the lung
      function test is not an ideal surrogate for short-term drug trials because it (1)
      does not provide information regarding disease activity or the underlying
      pathologic process, (2) cannot separate the various phenotypes of COPD, (3) is
      not specific for COPD, and (4) is relatively unresponsive to known therapies that
      prolong survival. Accordingly, there are large-scale studies presently underway
      to identify novel biomarkers in COPD. In this article, we discuss the current
      barriers of biomarker discovery and propose possible criteria and methods for
      developing novel biomarkers in COPD.

PMID- 19741267
TI  - Micro-computed tomography measurements of peripheral lung pathology in chronic
      obstructive pulmonary disease.
AB  - BACKGROUND: The smaller airways, < 2 mm in diameter, offer little resistance in
      normal lungs, but become the major site of obstruction in chronic obstructive
      pulmonary disease (COPD). OBJECTIVE: To examine bronchiolar remodeling and
      alveolar destruction in COPD using micro-computed tomography (micro-CT). METHODS:
      Micro-CT was used to measure the number and cross-sectional lumen area of
      terminal bronchioles (TB) and alveolar mean linear intercept (Lm) in 4 lungs
      removed from patients with very severe (GOLD-4) COPD and 4 unused donor lungs
      that served as controls. These lungs were inflated with air to a transpulmonary
      pressure (P(L)) of 30 cm H(2)O and held at P(L) 10 cm H(2)O while they were
      frozen solid in liquid nitrogen vapor. A high resolution CT scan was performed on
      the frozen specimen prior to cutting it into 2-cm thick transverse slices.
      Representative core samples of lung tissue 2 cm long and 1 cm in diameter cut
      from each slice were fixed at -80 degrees C in a 1% solution of gluteraldehyde in
      pure acetone, post-fixed in osmium, critically point dried, and examined by micro
      CT. RESULTS: A 10-fold reduction in terminal bronchiolar number and a 100-fold
      reduction in their minimal cross-sectional lumen area were measured in both
      emphysematous and non-emphysematous regions of the COPD lungs. CONCLUSIONS: The
      centrilobular emphysematous phenotype of COPD is associated with narrowing and
      obliteration of the terminal bronchioles that begins prior to the onset of
      emphysematous destruction.

PMID- 19741268
TI  - Testing drugs in animal models of cigarette smoke-induced chronic obstructive
      pulmonary disease.
AB  - Animal models of cigarette smoke-induced chronic obstructive pulmonary disease
      (COPD) provide potentially useful ways to test drug therapies, either by direct
      administration of the treatment of interest, or by use of genetically modified
      animals that mimic the actions of the drug of interest. Evaluation of the
      potential effects of a drug in animal models requires a long-term (generally 6
      mo) smoke exposure to produce/prevent lesions because acute models do not
      completely predict chronic events. There are now more than 30 chronic studies in
      the literature which, in aggregate, show that antiproteolytic therapies,
      antiinflammatory therapies, and antioxidant therapies substantially or completely
      prevent emphysema, small airway remodeling, and pulmonary hypertension in
      laboratory animals. However, the few corresponding trials in humans (anti-TNF
      alpha therapy, PDE4 inhibitors) have produced only minor improvements or failed
      to prevent disease progression. New data from our laboratory indicates that, at
      least for murine emphysema, the development of disease goes through different
      phases, with early repair and late failure to repair smoke-induced damage. These
      observations suggest that the potential effects of drug treatment in humans may
      vary depending on the stage of the disease and that treatment may be more
      effective in relatively early disease. An additional complicating factor is that
      interventions that ameliorate emphysema may or may not prevent small airway
      remodeling and/or pulmonary hypertension, suggesting that different therapeutic
      approaches may be needed for the various different anatomic lesions of COPD.

PMID- 19741269
TI  - New and controversial therapies for chronic obstructive pulmonary disease.
AB  - There is a medical need in chronic obstructive pulmonary disease (COPD) for novel
      therapies with improved anti-inflammatory activity and the potential to affect
      disease progression. The concept of "super bronchodilators" is currently in
      development. Nonsteroidal antiinflammatory approaches are now being developed and
      are going under investigation. Restoration of steroid sensitivity is also a
      potential target in COPD. This could be done by increasing HDAC-2 expression
      and/or activation, by decreasing p38-kinase or delta-isoform of PI3K. Disease
      modification that may impact on long-term health status and survival of the
      patient is the primary and most challenging target for novel therapy in COPD.
      There is need, however, for new methods and biomarkers to follow disease
      progression. There has been significant innovation in the nonpharmacological
      management of COPD including team-based approaches with collaborative self
      management. Information and guidelines about self-management, coupled with
      interventions that provide patients with needed skills to increase their
      confidence, have potential impact on patient health. Recently, it has been shown
      that self-management programs reduce the probability of COPD hospital admissions.
      We should certainly be enthusiastic about these results, but there is need to
      increase our understanding of the relative effectiveness of specific components
      and how to best support COPD patients in self-management. Conceptualization of a
      research plan for COPD self-management is needed for future research to be
      successful.

PMID- 19741270
TI  - The Kruppel-like zinc finger protein ZNF224 recruits the arginine
      methyltransferase PRMT5 on the transcriptional repressor complex of the aldolase
      A gene.
AB  - Gene transcription in eukaryotes is modulated by the coordinated recruitment of
      specific transcription factors and chromatin-modulating proteins. Indeed, gene
      activation and/or repression is/are regulated by histone methylation status at
      specific arginine or lysine residues. In this work, by co-immunoprecipitation
      experiments, we demonstrate that PRMT5, a type II protein arginine
      methyltransferase that monomethylates and symmetrically dimethylates arginine
      residues, is physically associated with the Kruppel-like associated box-zinc
      finger protein ZNF224, the aldolase A gene repressor. Moreover, chromatin
      immunoprecipitation assays show that PRMT5 is recruited to the L-type aldolase A
      promoter and that methylation of the nucleosomes that surround the L-type
      promoter region occurs in vivo on the arginine 3 of histone H4. Consistent with
      its association to the ZNF224 repressor complex, the decrease of PRMT5 expression
      produced by RNA interference positively affects L-type aldolase A promoter
      transcription. Finally, the alternating occupancy of the L-type aldolase A
      promoter by the ZNF224-PRMT5 repression complex in proliferating and growth
      arrested cells suggests that these regulatory proteins play a significant role
      during the cell cycle modulation of human aldolase A gene expression. Our data
      represent the first experimental evidence that protein arginine methylation plays
      a role in ZNF224-mediated transcriptional repression and provide novel insight
      into the chromatin modifications required for repression of gene transcription by
      Kruppel-like associated box-zinc finger proteins.

PMID- 19741271
TI  - Indoleamine 2,3-dioxygenase tissue distribution and cellular localization in
      mice: implications for its biological functions.
AB  - Earlier studies have suggested that indoleamine 2,3-dioxygenase (IDO) has a wide
      tissue distribution in mammals. However, detailed information on its cellular
      localization and also the levels of expression in various tissues is still
      scarce. In the present study, we sought to determine the cellular localization of
      IDO and also to quantify the level of its expression in various mouse tissues by
      using the branched DNA signal amplification assay, Western blotting, and
      immunohistochemical staining. The highest levels of constitutive IDO expression
      were found to be selectively present in the caput of epididymis, except for its
      initial segment. IDO expression was also detected inside the luminal compartment
      and even in the stereocilia within this region. In the prostate, high levels of
      IDO were selectively expressed in the capsular cells. In addition, high levels of
      IDO expression were also selectively detected in certain types of cells in the
      placenta, spleen, thymus, lung, and digestive tract. Notably, the morphological
      features of most of the positively stained cells in these organs closely
      resembled those of antigen-presenting cells. Based on the tissue distribution and
      cellular localization characteristics of IDO, it is hypothesized that its
      expression may serve two main functions: one is to deplete tryptophan in an
      enclosed microenvironment (such as in the epididymal duct lumen) to prevent
      bacterial or viral infection, and the other is to produce bioactive tryptophan
      catabolites that would serve to suppress T-cell-mediated immune responses against
      self-antigens, fetal antigens, or allogeneic antigens, in different situations.

PMID- 19741272
TI  - Identification and isolation of an azoreductase from Enterococcus faecium.
AB  - Azo dyes are commonly used in many commercial industries. Some of the azo dyes
      can produce carcinogenic compounds after being metabolized by azoreductase.
      Several human intestinal microbiota possess azoreductase activity which plays an
      important role in the toxicity and mutagenicity of these azo dye compounds. The
      acpD gene product (AzoEf1) responsible for the azoreductase activity of
      Enterococcus faecium, an intestinal bacterium, was heterologously expressed,
      purified and characterized. The protein sequence shares 67% identity with the
      azoreductase from Enterococcus faecalis, AzoA. Although AzoEf1 possesses many
      commonalities with AzoA, there are differences in coenzyme preference, residues
      associated with FMN binding, substrate specificity, and specific activity. AzoEf1
      utilized both NADH and NADPH for the reduction of azo dyes, and it contains a
      leucyl residue at position 104 and threonyl residue at position 19 which differ
      from AzoA at the active site. Its specific activity was 5095 M/min/mg and its
      catalytic efficiency for Methyl red reduction was lower than AzoA.

PMID- 19741273
TI  - Geant4 simulations of proton beam transport through a carbon or beryllium
      degrader and following a beam line.
AB  - Monte Carlo simulations based on the Geant4 simulation toolkit were performed for
      the carbon wedge degrader used in the beam line at the Center of Proton Therapy
      of the Paul Scherrer Institute (PSI). The simulations are part of the beam line
      studies for the development and understanding of the GANTRY2 and OPTIS2 treatment
      facilities at PSI, but can also be applied to other beam lines. The simulated
      stopping power, momentum distributions at the degrader exit and beam line
      transmission have been compared to accurate benchmark measurements. Because the
      beam transport through magnetic elements is not easily modeled using Geant4a
      connection to the TURTLE beam line simulation program was made. After adjusting
      the mean ionization potential of the carbon degrader material from 78 eV to 95
      eV, we found an accurate match between simulations and benchmark measurements, so
      that the simulation model could be validated. We found that the degrader does not
      completely erase the initial beam phase space even at low degraded beam energies.
      Using the validation results, we present a study of the usability of beryllium as
      a degrader material (mean ionization potential 63.7 eV). We found an improvement
      in the transmission of 30-45%, depending on the degraded beam energy, the higher
      value for the lower energies.

PMID- 19741274
TI  - Performance comparison between total variation (TV)-based compressed sensing and
      statistical iterative reconstruction algorithms.
AB  - Of all available reconstruction methods, statistical iterative reconstruction
      algorithms appear particularly promising since they enable accurate physical
      noise modeling. The newly developed compressive sampling/compressed sensing (CS)
      algorithm has shown the potential to accurately reconstruct images from highly
      undersampled data. The CS algorithm can be implemented in the statistical
      reconstruction framework as well. In this study, we compared the performance of
      two standard statistical reconstruction algorithms (penalized weighted least
      squares and q-GGMRF) to the CS algorithm. In assessing the image quality using
      these iterative reconstructions, it is critical to utilize realistic background
      anatomy as the reconstruction results are object dependent. A cadaver head was
      scanned on a Varian Trilogy system at different dose levels. Several figures of
      merit including the relative root mean square error and a quality factor which
      accounts for the noise performance and the spatial resolution were introduced to
      objectively evaluate reconstruction performance. A comparison is presented
      between the three algorithms for a constant undersampling factor comparing
      different algorithms at several dose levels. To facilitate this comparison, the
      original CS method was formulated in the framework of the statistical image
      reconstruction algorithms. Important conclusions of the measurements from our
      studies are that (1) for realistic neuro-anatomy, over 100 projections are
      required to avoid streak artifacts in the reconstructed images even with CS
      reconstruction, (2) regardless of the algorithm employed, it is beneficial to
      distribute the total dose to more views as long as each view remains quantum
      noise limited and (3) the total variation-based CS method is not appropriate for
      very low dose levels because while it can mitigate streaking artifacts, the
      images exhibit patchy behavior, which is potentially harmful for medical
      diagnosis.

PMID- 19741275
TI  - Nanoparticle temperature estimation in combined ac and dc magnetic fields.
AB  - The harmonics produced by the nonlinear magnetization of superparamagnetic
      nanoparticles have been utilized in a number of budding medical devices. Here we
      expand on an earlier technique for quantitatively measuring nanoparticle
      temperature in a purely ac field by including the presence of a static field. The
      ability to quantify nanoparticle temperature by tracking changes in the 4th/2nd
      harmonic ratio is presented and shown to achieve an accuracy of 0.79 K. The
      advantage of even harmonics, issues with odd harmonics in the presence of a
      static field and the potential for future incorporation into an imaging system
      are discussed.

PMID- 19741276
TI  - Fourier component imaging of water resonance in the human breast provides markers
      for malignancy.
AB  - The purpose of this paper is to demonstrate that voxels with inhomogeneously
      broadened water resonances, as revealed by high spectral and spatial resolution
      (HiSS) MRI, correlate with underlying tumor pathology findings, and thus carry
      diagnostically useful information. Thirty-four women with mammographically
      suspicious breast lesions were imaged at 1.5 T, using high-resolution echo-planar
      spectroscopic imaging. Fourier component images (FCIs) of the off-peak spectral
      signal were generated, and clusters of voxels with significant inhomogeneous
      broadening (broadened clusters) were identified and correlated to biopsy results.
      Inhomogeneously broadened clusters were found significantly more frequently in
      malignant than in benign lesions. A larger percentage of broadened cluster voxels
      were found inside the malignant versus benign lesions. The high statistical
      significance for separation of benign and malignant lesions was robust over a
      large range of post-processing parameters, with a maximum ROC area under curve of
      0.83. In the human breast, an inhomogeneously broadened water resonance can serve
      as a correlate marker for malignancy and is likely to reflect the underlying
      anatomy or physiology.

PMID- 19741277
TI  - The evaluation of 6 and 18 MeV electron beams for small animal irradiation.
AB  - A small animal irradiator is critical for providing optimal radiation dose
      distributions for pre-clinical animal studies. This paper focuses on the
      evaluation of using 6 or 18 MeV electron beams as small animal irradiators.
      Compared with all other prototypes which use photons to irradiate small animals,
      an electron irradiator has many advantages in its shallow dose distribution. Two
      major approaches including simulation and measurement were used to evaluate the
      feasibility of applying electron beams in animal irradiation. These simulations
      and measurements were taken in three different fields (a 6 cm x 6 cm square
      field, and 4 mm and 30 mm diameter circular fields) and with two different
      energies (6 MeV and 18 MeV). A PTW Semiflex chamber in a PTW-MP3 water tank, a
      PTW Markus chamber type 23343, a PTW diamond detector type 60003 and KODAK XV
      films were used to measure PDDs, lateral beam profiles and output factors for
      either optimizing parameters of Monte Carlo simulation or to verify Monte Carlo
      simulation in small fields. Results show good agreement for comparisons of
      percentage depth doses (<or=2.5% for 6 MeV e; <or=1.8% for 18 MeV e) and profiles
      (FWHM <or= 0.5 mm) between simulations and measurements on the 6 cm field.
      Greater deviation can be observed in the 4 mm field, which is mainly caused by
      the partial volume effects of the detectors. The FWHM of the profiles for the 18
      MeV electron beam is 32.6 mm in the 30 mm field, and 4.7 mm in the 4 mm field at
      d(90). It will take 1-13 min to complete one irradiation of 5-10 Gy. In addition,
      two different digital phantoms were also constructed, including a homogeneous
      cylindrical water phantom and a CT-based heterogeneous mouse phantom, and were
      implemented into Monte Carlo to simulate dose distribution with different
      electron irradiations.

PMID- 19741278
TI  - Monte Carlo dose mapping on deforming anatomy.
AB  - This paper proposes a Monte Carlo-based energy and mass congruent mapping (EMCM)
      method to calculate the dose on deforming anatomy. Different from dose
      interpolation methods, EMCM separately maps each voxel's deposited energy and
      mass from a source image to a reference image with a displacement vector field
      (DVF) generated by deformable image registration (DIR). EMCM was compared with
      other dose mapping methods: energy-based dose interpolation (EBDI) and trilinear
      dose interpolation (TDI). These methods were implemented in EGSnrc/DOSXYZnrc,
      validated using a numerical deformable phantom and compared for clinical CT
      images. On the numerical phantom with an analytically invertible deformation map,
      EMCM mapped the dose exactly the same as its analytic solution, while EBDI and
      TDI had average dose errors of 2.5% and 6.0%. For a lung patient's IMRT treatment
      plan, EBDI and TDI differed from EMCM by 1.96% and 7.3% in the lung patient's
      entire dose region, respectively. As a 4D Monte Carlo dose calculation technique,
      EMCM is accurate and its speed is comparable to 3D Monte Carlo simulation. This
      method may serve as a valuable tool for accurate dose accumulation as well as for
      4D dosimetry QA.

PMID- 19741279
TI  - Exact iterative reconstruction for the interior problem.
AB  - There is a trend in single photon emission computed tomography (SPECT) that small
      and dedicated imaging systems are becoming popular. For example, many companies
      are developing small dedicated cardiac SPECT systems with different designs.
      These dedicated systems have a smaller field of view (FOV) than a full-size
      clinical system. Thus data truncation has become the norm rather than the
      exception in these systems. Therefore, it is important to develop region of
      interest (ROI) reconstruction algorithms using truncated data. This paper is a
      stepping stone toward this direction. This paper shows that the common generic
      iterative image reconstruction algorithms are able to exactly reconstruct the ROI
      under the conditions that the convex ROI is fully sampled and the image value in
      a sub-region within the ROI is known. If the ROI includes a sub-region that is
      outside the patient body, then the conditions can be easily satisfied.

PMID- 19741280
TI  - Modifying proton fluence spectra to generate spread-out Bragg peaks with laser
      accelerated proton beams.
AB  - Currently, energy spectra of laser accelerated proton beams are far from being
      monoenergetic. For their application in radiation therapy, energy selection
      systems using magnetic fields have been proposed to single out particles with the
      desired energy. These systems allow the choice of protons between a lowest and a
      highest energy. In this work, we present a slight modification that allows us to
      influence the relative number of particles per energy bin. In fact, the
      transmitted spectrum can be shaped in such a way that it corresponds to a full
      spread out Bragg peak delivered simultaneously. This change of the spectrum can
      be achieved by inserting suitably formed scattering material at the central plane
      of the energy selection system where the particles are separated in space
      depending on their energy. With the help of Monte Carlo simulations we analysed
      both simple wedge geometries and various stacks of lead slices. We found that
      these configurations can provide energy spectra that naturally produce spread out
      Bragg peaks within one laser shot. This increases the particle efficiency of the
      whole system and makes laser accelerated protons more suitable for radiation
      therapy.

PMID- 19741281
TI  - Desipramine induces disorder in cholesterol-rich membranes: implications for
      viral trafficking.
AB  - In this study, the effect of desipramine (DMI) on phospholipid bilayers and
      parvoviral entry was elucidated. In atomistic molecular dynamics simulations, DMI
      was found to introduce disorder in cholesterol-rich phospholipid bilayers. This
      was manifested by a decrease in the deuterium order parameter S(CD) as well as an
      increase in the membrane area. Disordering of the membrane suggested DMI to
      destabilize cholesterol-rich membrane domains (rafts) in cellular conditions. To
      relate the raft disrupting ability of DMI with novel biological relevance, we
      studied the intracellular effect of DMI using canine parvovirus (CPV), a virus
      known to interact with endosomal membranes and sphingomyelin, as an intracellular
      probe. DMI was found to cause retention of the virus in intracellular vesicular
      structures leading to the inhibition of viral proliferation. This implies that
      DMI has a deleterious effect on the viral traffic. As recycling endosomes and the
      internal vesicles of multivesicular bodies are known to contain raft components,
      the effect of desipramine beyond the plasma membrane step could be caused by raft
      disruption leading to impaired endosomal function and possibly have direct
      influence on the penetration of the virus through an endosomal membrane.

PMID- 19741282
TI  - Molecular dynamics study of the RNA ring nanostructure: a phenomenon of self
      stabilization.
AB  - We study mechanical and thermodynamic properties of RNA nanostructures focusing
      on a hexagonal nanoring discussed in Yingling and Shapiro (2007 Nano Lett. 7
      2328). We are concerned with the following main issues: (i) the stability of the
      nanoring versus temperature; (ii) the effect of the environment (solvent,
      counterions) on its stability; (iii) conformations and dynamics under external
      force. The process of evaporation of the ions from the ring upon temperature drop
      has been found, demonstrating a surprising feature-the uptake of ions by the
      nanoring increases with the temperature. The connection of this behavior to the
      dielectric constant of water, hydration and structural changes in the nanoring is
      discussed. Several properties of the nanoring, such as elastic and transport
      coefficients, have been determined. A measure of the tensile elasticity of the
      ring against its uniform 2D in-plane compression has been given, as K(eff) < or =
      0.01 GPa, which is a much lower value compared to typical values found for soft
      matter other than RNA.

PMID- 19741283
TI  - Why a special issue of JIDC on enteric fever?

PMID- 19741284
TI  - The importance of generating evidence on typhoid fever for implementing
      vaccination strategies.

PMID- 19741285
TI  - The burden of enteric fever.
AB  - Enteric fever is a disease of developing countries associated with poor public
      health and low socio-economic indices. Cases of enteric fever occurring in
      travelers returning to the United States and the UK suggest that it is present
      across the developing world but that the Indian subcontinent represents a hotspot
      of disease activity. The best figures available for the global burden of enteric
      fever support this and suggest that Africa (50/ 100,000) has a far lower burden
      of disease than Asia (274/100,000). However these figures are based mainly on
      data for typhoid fever in Asia and the data for returning travelers is biased by
      preferred travel destinations. Given that most socio-economic indices, including
      known risk factors for enteric fever, such as provision of safe drinking water
      and sanitation, are much lower in most parts of Africa than in South-East and
      South-Central Asia it seems remarkable that Africa has such a low burden of
      disease. In such a scenario, rather than comparing whole continents, it may be
      more relevant to estimate region-specific burden of disease. It is clear is that
      there is an urgent need for more population-based studies of typhoid fever
      incidence in different parts of Africa to clarify the typhoid fever situation for
      the continent and so guide public health intervention.

PMID- 19741286
TI  - Clinical pathogenesis of typhoid fever.
AB  - Human infections with Salmonella enterica results in two major groups of
      diseases: gastroenteritis and typhoid fever. Clinical observations suggest that
      gastroenteritis, caused by non-typhoidal Salmonella serovars, is characterized by
      a massive neutrophil influx, which keeps the infection localized to the
      intestinal mucosa. In contrast, the absence of neutrophilic intestinal
      infiltrates in the acute phase of typhoid fever suggests a propensity for
      typhoidal Salmonella serovars (S. Typhi, S. Paratyphi A, S. Paratyphi B and S.
      Paratyphi C) to evade aspects of the innate immune response and cause a systemic
      infection. The fact that there are no virulence genes shared by typhoidal
      Salmonella serovars that are absent from non-typhoidal Salmonella serovars,
      suggests that this innate immune evasion is mediated by different mechanisms in
      different typhoidal serovars. This review discusses what is known about the
      clinical pathogenesis of typhoid fever.

PMID- 19741287
TI  - SPI-7: Salmonella's Vi-encoding Pathogenicity Island.
AB  - Salmonella Pathogenicity Island-7 (SPI-7) is a large, mosaic, genetic island,
      found in several serovars of Salmonella enterica subsp. enterica associated with
      systemic disease. As well as encoding genes which may aid its own transmission,
      it carries genes for potential virulence factors such as Vi antigen, SopE
      effector and type IVB pili. The stability of SPI-7 is of interest with respect to
      typhoid fever and related vaccines.

PMID- 19741288
TI  - IncHI plasmids, a dynamic link between resistance and pathogenicity.
AB  - Plasmids of incompatibility group (Inc) HI1 are important vectors of antibiotic
      resistance in both of the major causal agents of enteric fever: Salmonella
      enterica subspecies enterica serovar Typhi and S. Paratyphi A. In S. Typhi,
      IncHI1 plasmids appeared in the 1970s and spread globally. In some circumstances
      they are maintained within the bacterial population even in the absence of
      selection from antibiotics. The low cost associated with IncH plasmids in
      Salmonella is due, in part, to the presence of a plasmid gene encoding an H-NS
      like global regulator which acts co-operatively with chromosomally encoded H-NS.
      Very recently, IncHI1 plasmids have crossed from S. Typhi into S. Paratyphi A;
      the acquisition of drug resistance and possibly other phenotypic traits encoded
      by IncHI1 plasmids has increased the virulence potential of this neglected
      pathogen. There is no vaccine for S. Paratyphi A and resistance to the current
      drugs of choice, the fluoroquinolones, is also spreading rapidly. There is a
      conserved backbone to all IncH plasmids but variation occurs in regions of the
      plasmids associated with antibiotic resistance. These IncHI1 plasmids are
      allowing major human pathogens to sample genes available in their environment,
      the human gut, and will be maintained by enhancing the competitive advantage of
      the bacterial host. Therefore competition between closely related resistance
      plasmids will probably increase the transmission of enteric fever by enhancing
      the fitness of their bacterial hosts.

PMID- 19741289
TI  - Enteric fever in endemic areas of Indonesia: an increasing problem of resistance.
AB  - Reported levels of antibiotic resistance in Salmonella Typhi from South Sulawesi,
      Indonesia were very low (< 1%) before 2001 and chloramphenicol remained the
      treatment of choice. Since 2001 however resistance has been rising and in 2007
      6.8% of isolates were resistant to all three first line drugs: Ampicillin,
      chloramphenicol and co-trimoxazole. Ciprofloxacin resistance is currently at 3.90
      %. At the same time there has been an increase in the number of reported cases.
      This may be because of improved diagnostics or it may be a genuine outbreak of
      drug resistant S. Typhi. In conclusion drug resistant typhoid fever will become a
      serious problem in Indonesia in the future, requiring the use of expensive drugs
      for the treatment of typhoid. A concerted effort is needed by the medical
      services to implement reliable diagnosis so that treatment or vaccination can be
      used to control the spread of drug resistant typhoid fever.

PMID- 19741290
TI  - Enteric fever in south China: Guangxi province.
AB  - Guangxi is a province of China endemic for enteric fever. Salmonella enterica
      serovar Paratyphi A has been found to be causing more and more enteric fever
      episodes in the last 10 years, evident not only from routine surveillance but
      also from prospective population-based surveillance. The prevalent pattern of
      paratyphoid seen was different from typhoid since it mainly occurred in
      outbreaks. Almost all strains collected from different areas and years in Guangxi
      were resistance to nalidixic acid, which is an indicator of reduced efficacy of
      ciprofloxacin treatment. The emergence of epidemic paratyphoid fever occurred
      after large-scale use of the typhoid Vi vaccine, but little is know about why it
      emerged. This is of particular concern in the post Vi vaccine era due to the
      emergence and worldwide spread of multi-drug resistant S. Paratyphi A strains and
      the lack of a vaccine.

PMID- 19741291
TI  - Antibiotic resistance among Salmonella enterica serovars Typhi and Paratyphi A in
      Pakistan (2001-2006).
AB  - OBJECTIVES: To compare antimicrobial resistance in S. Typhi and S. Paratyphi A
      isolates from Pakistan. METHODS: Blood samples were collected through > 175
      laboratory collection points in major cities and towns across the country. The
      study included 3,671 S. Typhi and 1,475 S. Paratyphi A isolates (2001-2006).
      Multidrug resistance (MDR) was defined as resistance to first-line agents co
      trimoxazole, chloramphenicol and ampicillin. RESULTS: In total, 79.3% S. Typhi
      and 59.9% S. Paratyphi A were isolated from patients under 15 years of age.
      During the study period, the MDR rate increased in S. Typhi (34.2 to 48.5%
      p<0.001). Quinolone resistance (MIC> 1 microg/ml) increased in both S. Typhi (1.6
      to 64.1% p<0.001) and S. Paratyphi A (0 to 47% p<0.001). The increase in the
      proportion of strains showing high level quinolone resistance (MIC > 4 microg/ml)
      was greater in S. Paratyphi A when compared to S. Typhi. Resistance to first-line
      drugs was higher in those <15 years of age whereas quinolone resistance was
      higher in older patients. CONCLUSION: Differences between S. Typhi and S.
      Paratyphi A, in terms of evolution of resistance to first-line agents and to
      quinolones, are evident in this population. The rapid increase in quinolone
      resistance in S. Paratyphi A when compared to S. Typhi is concerning and requires
      further study.

PMID- 19741292
TI  - Emergence of plasmid-mediated multidrug resistance in epidemic and non-epidemic
      strains of Salmonella enterica serotype Typhi from Jordan.
AB  - BACKGROUND: Enteric fever caused by Salmonella enterica serovar Typhi has not
      been adequately explored in Jordan. METHODOLOGY: In this study we investigated
      antibiotic resistance patterns and resistance determinants coupled with
      fingerprint methods of forty-eight isolates of S. Typhi obtained from 113
      patients with suspected enteric fever admitted at six governmental hospitals in
      different directorates in Jordan. Twenty-four isolates were from an outbreak of
      typhoid fever that occurred between October 2004 and January 2005, and another
      twenty-four were from sporadic cases from 2005. RESULTS: All isolates of S. Typhi
      were resistant to streptomycin. A multidrug resistant (MDR) pattern of
      ampicillin, chloramphenicol, co-trimoxazole with tetracycline and streptomycin (R
      type ACCoTS) was found in 58% of the epidemic strains causing the outbreak and in
      98% of the strains from sporadic cases. MDR isolates harbored a single IncHI1
      plasmid containing a class 1 integron (dfrA7). Plasmid conjugation studies
      demonstrated a genetic transfer of resistance (ACCoT). S. Typhi isolates were all
      sensitive to fluoroquinolones and cefotaxime, the alternative drugs recommended
      for treatment of typhoid fever. The genomic analysis using PFGE showed: a) the
      outbreak was caused by an introduced circulating clone with/without an MDR
      plasmid, and b) isolates from the sporadic cases from 2005 are the same MDR clone
      that persisted and spread in the country. CONCLUSION: The emergence of MDR S.
      Typhi strains is a majorn important public health issue in Jordan. This study
      should guide selection of effective antibiotic therapy for the treatment of
      typhoid and monitoring of the spread of MDR of S. Typhi.

PMID- 19741293
TI  - Association of carcinoma of the gallbladder with typhoid carriage in a typhoid
      endemic area using nested PCR.
AB  - BACKGROUND: Although well studied the association between chronic typhoid carrier
      state and carcinoma of the gallbladder (CaGB) remains unproven. METHODOLOGY: The
      study was performed at a tertiary care medical center in North India and involved
      52 patients with CaGB, 223 patients with benign gallbladder diseases, 508 healthy
      individuals and, 424 corpses. For the detection of Salmonella enterica serovar
      Typhi, hepatobiliary specimens were subjected to DNA extraction for specific
      nested- PCR amplification of the S. Typhi flagellin gene. Anti-Vi S. Typhi
      antibodies were detected in serum samples from patients by indirect
      haemagglutination. RESULTS: Thirty five of the 52 (67.3%) CaGB patients were PCR
      positive for the S. Typhi flagellin gene; significantly higher than for patients
      with benign gallbladder diseases (95/223, 42.6%; p<0.01) and corpses (35/424,
      8.2%; p<0.001). The numbers of individuals that had significant anti-Vi antibody
      titres (> or = 160) in their serum were 20/52 (38.5%) for CaGB patients, 31/223
      (13.9%) for patients with benign gallbladder diseases, and 47/508 (9.2%) for
      healthy individuals. CONCLUSIONS: Specific nested-PCR amplification of the S.
      Typhi flagellin gene in hepato-biliary specimens was more sensitive for detection
      of S. Typhi carriage than anti-Vi antibody titres in serum. The results
      demonstrate an association between typhoid carriage and gallbladder diseases,
      both CaGB and benign. S. Typhi specific immunosuppression is also suggested in
      patients with gallbladder diseases.

PMID- 19741294
TI  - Antibodies to the Vi capsule of Salmonella Typhi in the serum of typhoid patients
      and healthy control subjects from a typhoid endemic region.
AB  - BACKGROUND: There is very little published data on the antibody response to the
      Vi capsular polysaccharide (Vi-CPS) of S. Typhi during naturally acquired typhoid
      fever in an endemic area. METHODOLOGY: An indirect ELISA, using tyraminated,
      purified Vi-CPS, was used to assay anti-Vi-CPS antibodies from typhoid fever
      cases and controls living in the Ho Chi Minh City and Mekong Delta region of Viet
      Nam. RESULTS: Antibody response to Vi-CPS is significantly higher in typhoid
      patients who have been ill for more than two weeks than those who are in the
      first two weeks of illness. The anti-Vi-CPS response is similar for adults and
      children. Anti-Vi-CPS antibodies can be detected in the sera of non-typhoid
      patients. The frequency with which this occurs increases with age, probably
      reflecting increased exposure to S. Typhi. CONCLUSIONS: Anti-Vi_CPS is elicited
      in persons infected with S. Typhi but only after a prolonged duration of illness.
      Vaccine trials have shown anti-Vi-CPS antibodies to be protective; thus early
      treatment of typhoid patients, i.e. in the first two week of illness before the
      Vi-CPS response is elicited, may inhibit the development of this protective
      immune response.

PMID- 19741295
TI  - Mimotopes of heat shock proteins of Salmonella enterica serovar Typhi identified
      from phage-displayed peptide library.
AB  - BACKGROUND: Heat shock proteins (HSPs) are known to be involved in the
      pathogenesis of Salmonella enterica serovar Typhi (S. Typhi), the causative agent
      of typhoid fever. The objective of this study was to apply a phage display
      library to identify mimotopes of two HSPs, HSP90 and DnaK in S. Typhi.
      METHODOLOGY: A 12-mer random peptide library expressed on the surface of the
      filamentous phage, M13, was used to select the mimotopes of two S. Typhi heat
      shock proteins by biopanning with monoclonal antibodies (mAbs), DnaK and HSP90.
      The immunogenicity of the selected peptides was determined through binding
      affinity with polyclonal antibodies from pooled typhoid-confirmed patients' sera
      and purified HSPs mAb using Western blotting and ELISA. RESULTS: Five rounds of
      biopanning resulted in enrichment of phage clones expressing the binding motifs
      TDxSTRP and FPSHYWLYPPPT, respectively. The selected peptides showed strong
      immunoreactivity with patients' sera. Thus, monoclonal antibodies against HSP and
      patient sera can select common mimotopes from the random peptide library.
      CONCLUSION: These findings may provide fundamental information for further
      studies on diagnostic application or vaccine design against this aetiologic agent
      of typhoid fever.

PMID- 19741296
TI  - A case report and review of the literature: ciprofloxacin resistant Salmonella
      enterica serovar Typhi in India.
AB  - BACKGROUND: Enteric fever is a major public health problem in India. The current
      treatment of choice is the fluoroquinolones. METHODS: The minimum inhibitory
      concentration (MIC) of ciprofloxacin was determined by E-test, HIMEDIA HiComb MIC
      test and agar dilution. RESULTS: An isolate of Salmonella enterica serovar Typhi
      (S. Typhi) from a case of enteric fever gave a ciprofloxacin MIC of 64 microg/ml.
      CONCLUSIONS: To our knowledge there have been no reports of such high-level
      resistance to ciprofloxacin in S. Typhi from southern India. HIMEDIA HiComb MIC
      test method is an alternative to the E-test. Ciprofloxacin resistant typhoid
      fever responds to treatment with ceftriaxone.

PMID- 19741297
TI  - Calcium/calmodulin-dependent protein kinase II links ER stress with Fas and
      mitochondrial apoptosis pathways.
AB  - ER stress-induced apoptosis is implicated in various pathological conditions, but
      the mechanisms linking ER stress-mediated signaling to downstream apoptotic
      pathways remain unclear. Using human and mouse cell culture and in vivo mouse
      models of ER stress-induced apoptosis, we have shown that cytosolic calcium
      resulting from ER stress induces expression of the Fas death receptor through a
      pathway involving calcium/calmodulin-dependent protein kinase IIgamma
      (CaMKIIgamma) and JNK. Remarkably, CaMKIIgamma was also responsible for processes
      involved in mitochondrial-dependent apoptosis, including release of mitochondrial
      cytochrome c and loss of mitochondrial membrane potential. CaMKII-dependent
      apoptosis was also observed in a number of cultured human and mouse cells
      relevant to ER stress-induced pathology, including cultured macrophages,
      endothelial cells, and neuronal cells subjected to proapoptotic ER stress.
      Moreover, WT mice subjected to systemic ER stress showed evidence of macrophage
      mitochondrial dysfunction and apoptosis, renal epithelial cell apoptosis, and
      renal dysfunction, and these effects were markedly reduced in CaMKIIgamma
      deficient mice. These data support an integrated model in which CaMKII serves as
      a unifying link between ER stress and the Fas and mitochondrial apoptotic
      pathways. Our study also revealed what we believe to be a novel proapoptotic
      function for CaMKII, namely, promotion of mitochondrial calcium uptake. These
      findings raise the possibility that CaMKII inhibitors could be useful in
      preventing apoptosis in pathological settings involving ER stress-induced
      apoptosis.

PMID- 19741298
TI  - The tumor-promoting actions of TNF-alpha involve TNFR1 and IL-17 in ovarian
      cancer in mice and humans.
AB  - Cytokines orchestrate the tumor-promoting interplay between malignant cells and
      the immune system. In many experimental and human cancers, the cytokine TNF-alpha
      is an important component of this interplay, but its effects are pleiotropic and
      therefore remain to be completely defined. Using a mouse model of ovarian cancer
      in which either TNF receptor 1 (TNFR1) signaling was manipulated in different
      leukocyte populations or TNF-alpha was neutralized by antibody treatment, we
      found that this inflammatory cytokine maintained TNFR1-dependent IL-17 production
      by CD4+ cells and that this led to myeloid cell recruitment into the tumor
      microenvironment and enhanced tumor growth. Consistent with this, in patients
      with advanced cancer, treatment with the TNF-alpha-specific antibody infliximab
      substantially reduced plasma IL-17 levels. Furthermore, expression of IL-1R and
      IL-23R was downregulated in CD4+CD25- cells isolated from ascites of ovarian
      cancer patients treated with infliximab. We have also shown that genes ascribed
      to the Th17 pathway map closely with the TNF-alpha signaling pathway in ovarian
      cancer biopsy samples, showing particularly high levels of expression of genes
      encoding IL-23, components of the NF-kappaB system, TGF-beta1, and proteins
      involved in neutrophil activation. We conclude that chronic production of TNF
      alpha in the tumor microenvironment increases myeloid cell recruitment in an IL
      17-dependent manner that contributes to the tumor-promoting action of this
      proinflammatory cytokine.

PMID- 19741299
TI  - Cdc42 is an antihypertrophic molecular switch in the mouse heart.
AB  - To improve contractile function, the myocardium undergoes hypertrophic growth
      without myocyte proliferation in response to both pathologic and physiologic
      stimulation. Various membrane-bound receptors and intermediate signal
      transduction pathways regulate the induction of cardiac hypertrophy, but the
      cardioprotective regulatory pathways or effectors that antagonize cardiac
      hypertrophy remain poorly understood. Here we identify the small GTPase Cdc42 as
      a signaling intermediate that restrained the cardiac growth response to
      physiologic and pathologic stimuli. Cdc42 was specifically activated in the heart
      after pressure overload and in cultured cardiomyocytes by multiple agonists. Mice
      with a heart-specific deletion of Cdc42 developed greater cardiac hypertrophy at
      2 and 8 weeks of stimulation and transitioned more quickly into heart failure
      than did wild-type controls. These mice also displayed greater cardiac
      hypertrophy in response to neuroendocrine agonist infusion for 2 weeks and, more
      remarkably, enhanced exercise-induced hypertrophy and sudden death. These
      pathologies were associated with an inability to activate JNK following
      stimulation through a MEKK1/MKK4/MKK7 pathway, resulting in greater cardiac
      nuclear factor of activated T cells (NFAT) activity. Restoration of cardiac JNK
      signaling with an Mkk7 heart-specific transgene reversed the enhanced growth
      effect. These results identify what we believe to be a novel antihypertrophic and
      protective cardiac signaling pathway, whereby Cdc42-dependent JNK activation
      antagonizes calcineurin-NFAT activity to reduce hypertrophy and prevent
      transition to heart failure.

PMID- 19741300
TI  - Potent inhibition of HIV-1 by TRIM5-cyclophilin fusion proteins engineered from
      human components.
AB  - New World monkeys of the genus Aotus synthesize a fusion protein (AoT5Cyp)
      containing tripartite motif-containing 5 (TRIM5) and cyclophilin A (CypA) that
      potently blocks HIV-1 infection. We attempted to generate a human HIV-1 inhibitor
      modeled after AoT5Cyp, by fusing human CypA to human TRIM5 (hT5Cyp). Of 13
      constructs, 3 showed substantial HIV-1-inhibitory activity when expressed in
      human cell lines. This activity required capsid binding by CypA and correlated
      with CypA linkage to the TRIM5a capsid-specificity determinant and the ability to
      form cytoplasmic bodies. CXCR4- and CCR5-tropic HIV-1 clones and primary isolates
      were inhibited from infecting multiple human macrophage and T cell lines and
      primary cells by hT5Cyp, as were HIV-2ROD, SIVAGMtan, FIVPET, and a circulating
      HIV-1 isolate previously reported to be AoT5Cyp resistant. The anti-HIV-1
      activity of hT5Cyp was surprisingly more effective than that of the well
      characterized rhesus TRIM5alpha, especially in T cells. hT5Cyp also blocked HIV-1
      infection of primary CD4+ T cells and macrophages and conferred a survival
      advantage to these cells without disrupting their function. Extensive attempts to
      elicit HIV-1 resistance to hT5Cyp were unsuccessful. Finally, Rag2-/-gammac-/-
      mice were engrafted with human CD4+ T cells that had been transduced by optimized
      lentiviral vectors bearing hT5Cyp. Upon challenge with HIV-1, these mice showed
      decreased viremia and productive infection in lymphoid organs and preserved
      numbers of human CD4+ T cells. We conclude that hT5Cyp is an extraordinarily
      robust inhibitor of HIV-1 replication and a promising anti-HIV-1 gene therapy
      candidate.

PMID- 19741302
TI  - Behavioural pharmacology of impulse control.

PMID- 19741301
TI  - Delay of smoking gratification as a laboratory model of relapse: effects of
      incentives for not smoking, and relationship with measures of executive function.
AB  - Nineteen nicotine-deprived cigarette smokers received monetary rewards for each
      minute they chose not to initiate smoking in 2-h laboratory sessions followed by
      a 30-min period of enforced abstinence from smoking. Reinforcer amounts were
      delivered according to one of three schedules: increasing, decreasing, and
      constant. Relapse time (time until first cigarette) was shortest in the
      decreasing condition, longest in the increasing condition, and intermediate in
      the constant condition. All differences were significant except in the constant
      decreasing comparison. The relationships between a battery of baseline
      assessments and relapse times were examined. Relapse times were predicted by
      delay-discounting coefficients (k) for $10 and $1000 in money and for $1000 of
      cigarettes. Relapse times were also predicted by the number of cigarettes smoked
      daily and a Wisconsin Card Sorting Test score. Performance on the Stroop Task and
      the Fagerstrom Test for Nicotine Dependence differentiated participants
      dichotomized into those who relapsed 'earlier' in sessions versus those who first
      smoked 'later'. The variability in some scores from smoking-urges and affect
      questionnaires administered after smoking-room sessions was explained by measures
      related to in-session nicotine intake. Results are discussed as they relate to
      contingency-management procedures, predictors of relapse, and the competing
      neurobehavioral decision systems theory of addiction.

PMID- 19741305
TI  - Concussion consensus: raising the bar and filling in the gaps.

PMID- 19741306
TI  - The International Olympic Committee (IOC) consensus statement on periodic health
      evaluation of elite athletes, March 2009.

PMID- 19741307
TI  - Influence of humeral torsion on interpretation of posterior shoulder tightness
      measures in overhead athletes.
AB  - OBJECTIVE: To measure the influence of humeral torsion on interpretation of
      clinical indicators of posterior shoulder tightness in overhead athletes. DESIGN:
      Cross-sectional control group comparison. SETTING: A university-based sports
      medicine research laboratory. PARTICIPANTS: Twenty-nine healthy intercollegiate
      baseball players and 25 college-aged control individuals with no history of
      participation in overhead athletics were enrolled. INTERVENTION: In all
      participants, bilateral humeral rotation and humeral horizontal adduction
      variables were measured with a digital inclinometry. Bilateral humeral torsion
      was measured with ultrasonography. MAIN OUTCOME MEASURES: Group and limb
      comparisons were made for clinical indicators of posterior shoulder tightness
      (humeral rotation and horizontal adduction variables) and humeral torsion
      variables. The relationship between humeral torsion and clinical indicators of
      posterior shoulder tightness were established. RESULTS: The dominant limb of the
      baseball players demonstrated greater humeral torsion, and less internal rotation
      and total rotation range of motion, compared with control participants and the
      nondominant limb in both groups. Once corrected for torsion, no group or limb
      differences in internal rotation were present. Statistically significant
      relationships existed between the amount of humeral torsion and measures of
      posterior shoulder tightness. CONCLUSIONS: Although limb differences in clinical
      indicators of posterior tightness exist in healthy overhead athletes, these
      measures appear to be influenced by humeral torsion rather than soft tissue
      tightness. Once torsion is accounted for, the limb differences observed
      clinically were minimal in healthy overhead athletes. When possible, accounting
      for humeral torsion when interpreting clinical measures of posterior shoulder
      tightness may aid in treatment decisions.

PMID- 19741308
TI  - Biomechanical and anatomic factors associated with a history of plantar fasciitis
      in female runners.
AB  - OBJECTIVE: To compare selected structural and biomechanical factors between
      female runners with a history of plantar fasciitis and healthy control subjects.
      DESIGN: Cross-sectional. SETTING: University of Delaware Motion Analysis
      Laboratory, Newark, Delaware; and University of Massachusetts Biomechanics
      Laboratory, Amherst, Massachusetts. PARTICIPANTS: Twenty-five female runners with
      a history of plantar fasciitis were recruited for this study. A group of 25 age-
      and mileage-matched runners with no history of plantar fasciitis served as
      control subjects. INTERVENTIONS: The independent variable was whether or not
      subjects had a history of plantar fasciitis. MAIN OUTCOME MEASURES: Subjects ran
      overground while kinematic and kinetic data were recorded using a motion capture
      system and force plate. Rearfoot kinematic variables of interest included peak
      dorsiflexion, peak eversion, time to peak eversion along with eversion excursion.
      Vertical ground reaction force variables included impact peak and the maximum
      instantaneous load rate. Structural measures were taken for calcaneal valgus and
      arch index during standing and passive ankle dorsiflexion range of motion.
      RESULTS: A significantly greater maximum instantaneous load rate was found in the
      plantar fasciitis group along with an increased ankle dorsiflexion range of
      motion compared with the control group. The plantar fasciitis group had a lower
      arch index compared with control subjects, but calcaneal valgus was similar
      between groups. No differences in rearfoot kinematics were found between groups.
      CONCLUSION: These data indicate that a history of plantar fasciitis in runners
      may be associated with greater vertical ground reaction force load rates and a
      lower medial longitudinal arch of the foot.

PMID- 19741309
TI  - The relationship of athlete-reported concussion symptoms and objective measures
      of neurocognitive function and postural control.
AB  - OBJECTIVE: Concussed athlete evaluations often include symptoms, balance, and
      neurocognitive assessments. We sought to identify the relationship between
      subjective symptom reports and objective clinical measures. DESIGN: A
      retrospective assessment. SETTING: A research laboratory. PATIENTS: Concussed
      collegiate-level athletes (N = 32, 19.7 years) evaluated pre- and postinjury
      (less than 48 hours). INTERVENTION: Each athlete completed an inventory of
      concussion-related symptoms, the NeuroCom Sensory Organization Test (SOT), and
      ImPACT neurocognitive assessment. Spearman correlations between balance symptoms
      and SOT scores and cognitive symptoms and ImPACT scores were completed. MAIN
      OUTCOME MEASURES: Symptoms related to balance and cognitive deficits, SOT
      composite balance and visual, vestibular, and somatosensory ratios, and ImPACT
      output scores. RESULTS: Significant Spearman correlations were noted between
      reports of "dizziness" and the SOT composite balance (rs = -0.55) and vestibular
      ratio (rs = -0.50). Similarly, "balance problems" were significantly correlated
      with composite balance (rs = -0.52) and the somatosensory (rs = -0.41), visual
      (rs = -0.39), and vestibular ratios (rs = -0.57). The cognitive symptom of
      "feeling mentally foggy" and ImPACT variables of reaction time (rs = 0.36) and
      "difficulty concentrating" and verbal memory score (rs = -0.41) were
      significantly related. Finally, reports of "difficulty remembering" were
      significantly related to the verbal memory score (rs = -0.48) and reaction time
      (rs = 0.36). CONCLUSIONS: These findings indicate self-report symptoms are
      associated with athlete deficits in postural control and cognitive function. The
      moderate relationship between the symptom reports and the objective measures
      warrants the continued use of all measures. A reduction in the number of symptoms
      concussed athletes respond to may be justified to reduce redundancy.

PMID- 19741310
TI  - Analysis of 10 years of injury in high school rodeo.
AB  - OBJECTIVE: To determine the injury rate of athletes participating in high school
      rodeo. DESIGN: Retrospective report review. SETTING: National High School rodeo
      finals from 1996 to 2005. PARTICIPANTS: High school athletes qualified for the
      rodeo competitions through state or national qualifying rounds. ASSESSMENT OF
      RISK FACTORS: Injury reports were documented by sports medicine personnel.
      Variables evaluated were injury density, frequency for mechanism of injury,
      injury location, injury type, and follow-up request. RESULTS: A total of 354
      injury incidents from 43,168 competitor exposures (CEs) resulted in a composite
      injury density of 8.20 per 1000 CE. Rough stock athletes accounted for 76.6% of
      all injuries. Bareback riders, followed by bull riders and saddle bronc riders,
      demonstrated injury densities of 31.9, 28.5, and 23.5 per 1000 CE, respectively.
      Most injuries (40.9%) were sustained while dismounting or being bucked off of the
      animal. Contusions, sprains, and strains were the most frequent injury types
      (27.4%, 18.6%, and 16.4%, respectively). The head and the shoulder (17.8% and
      11.35%, respectively) were the most commonly injured body parts. An incidence
      density of 0.7 per 1000 CE was found for injury requiring transport by ambulance.
      CONCLUSIONS: High school rodeo athletes sustain similar injuries to collegiate
      and professional rodeo athletes, indicating that addressing issues at the youth
      level may be of great benefit. To better provide prevention tools for rodeo
      athletes, mechanism of injury and methods to reduce buck-off need further
      inquiry.

PMID- 19741311
TI  - Surfing as a risk factor for gastroesophageal reflux disease.
AB  - OBJECTIVE: To compare the prevalence of gastroesophageal reflux disease (GERD) in
      surfers versus nonsurfers who participate in other sports activities based on the
      hypothesis that paddling in the prone position on hard surfboard surfaces leads
      to increased intra-abdominal pressure and GERD. STUDY DESIGN: A questionnaire
      survey using a modified Gastrointestinal Symptom Rating Scale. SETTING: Data
      obtained from surfers and nonsurfer athletes on the island of Oahu in the state
      of Hawaii. PARTICIPANTS: One hundred eighty-five surfers and 178 nonsurfers who
      participate in sports activities. ASSESSMENT OF RISK FACTORS: Surfer or nonsurfer
      status, type of surfboard used, frequency of surfing, and duration of surfing
      experience. MAIN OUTCOME MEASURES: The prevalence of reflux symptoms at least
      twice a week (GERD). RESULTS: The prevalence of GERD was significantly higher in
      short-board surfers than in nonsurfers with an odds ratio of 4.6 (28% versus 7%,
      P < 0.001) after adjustment for demographic variables using the multivariate
      regression model. GERD was more prevalent in short-boarders than long-boarders
      (28% and 12%, respectively). The prevalence of GERD increased significantly as
      both the frequency and duration of surfing experience increased (P < 0.001).
      CONCLUSION: Surfing is strongly associated with GERD. Short-board surfing appears
      to have a stronger association with GERD than long-board surfing.

PMID- 19741312
TI  - Supervised exercise in patients with impaired fasting glucose: impact on exercise
      capacity.
AB  - OBJECTIVE: To compare the effects of counseling alone with that of additional
      participation in supervised training courses on exercise capacity in patients
      with impaired fasting glucose. DESIGN: Randomized, controlled intervention trial
      using a nested cohort approach. SETTING: Primary care centers in western Austria.
      PATIENTS: Thirty-six patients with impaired fasting glucose (16 males, 20
      females; mean age, 57.5 +/- 6.9 years). INTERVENTIONS: Participants of both
      groups were instructed about the preventive effectiveness of changing their
      lifestyle, especially losing weight and increasing physical activity. One group
      had additionally been offered supervised, progressive, individually tailored
      aerobic exercise programs for 1 hour twice a week. MAIN OUTCOME MEASURES: Changes
      in the levels of exercise capacity, body mass, and fasting blood glucose.
      RESULTS: The subjects with supervised exercise participated in this program for
      1.8 hours (+/- 0.3) per week over 12 months. Supervised exercise was sufficient
      to maintain exercise capacity, whereas counseling alone was not (+4.4% versus 
      6.9%; P = 0.01). After the 12-month intervention period, body mass was reduced in
      the supervised exercise group (-3.0%) compared with the counseling alone group
      (+1.0%) (P = 0.03) and fasting plasma glucose levels had similarly improved by
      counseling for adequate lifestyle changes alone (-8.2%) and in combination with
      supervised exercise (-6.0%). CONCLUSION: In contrast to counseling alone, 2
      sessions of supervised training per week, besides the self-chosen physical
      activity and nutritional measures, are sufficient to maintain exercise capacity
      in patients with impaired fasting glucose.

PMID- 19741313
TI  - Three weeks of creatine monohydrate supplementation affects dihydrotestosterone
      to testosterone ratio in college-aged rugby players.
AB  - OBJECTIVE: This study investigated resting concentrations of selected androgens
      after 3 weeks of creatine supplementation in male rugby players. It was
      hypothesized that the ratio of dihydrotestosterone (DHT, a biologically more
      active androgen) to testosterone (T) would change with creatine supplementation.
      DESIGN: Double-blind placebo-controlled crossover study with a 6-week washout
      period. SETTING: Rugby Institute in South Africa. PARTICIPANTS: College-aged
      rugby players (n = 20) volunteered for the study, which took place during the
      competitive season. INTERVENTIONS: Subjects loaded with creatine (25 g/day
      creatine with 25 g/day glucose) or placebo (50 g/day glucose) for 7 days followed
      by 14 days of maintenance (5 g/day creatine with 25 g/day glucose or 30 g/day
      glucose placebo). MAIN OUTCOME MEASURES: Serum T and DHT were measured and ratio
      calculated at baseline and after 7 days and 21 days of creatine supplementation
      (or placebo). Body composition measurements were taken at each time point.
      RESULTS: After 7 days of creatine loading, or a further 14 days of creatine
      maintenance dose, serum T levels did not change. However, levels of DHT increased
      by 56% after 7 days of creatine loading and remained 40% above baseline after 14
      days maintenance (P < 0.001). The ratio of DHT:T also increased by 36% after 7
      days creatine supplementation and remained elevated by 22% after the maintenance
      dose (P < 0.01). CONCLUSIONS: Creatine supplementation may, in part, act through
      an increased rate of conversion of T to DHT. Further investigation is warranted
      as a result of the high frequency of individuals using creatine supplementation
      and the long-term safety of alterations in circulating androgen composition.
      STATEMENT OF CLINICAL RELEVANCE: Although creatine is a widely used ergogenic
      aid, the mechanisms of action are incompletely understood, particularly in
      relation to dihydrotestosterone, and therefore the long-term clinical safety
      cannot be guaranteed.

PMID- 19741314
TI  - Evaluation of nutritional intake in Canadian high-performance athletes.
AB  - OBJECTIVE: To determine the nutritional intake of Canadian high-performance
      athletes. DESIGN: Prospective survey study. SETTING: Canadian sport center
      athletes. PARTICIPANTS: Three hundred twenty-four high-performance athletes (114
      males and 201 females; mean age 21.3 +/- 13 years) from 8 Canadian sport centers
      participated in the study. INTERVENTION: Subjects prospectively completed 3-day
      dietary records, reporting all food, fluid, and supplement consumption. MAIN
      OUTCOME MEASURES: Dietary records were analyzed for total calories,
      macronutrients, and micronutrients for food alone and food plus supplements for
      all subjects collectively and according to gender and competitive event. RESULTS:
      Average daily energy intake was 2533 +/- 843 Kcal/day with males consuming more
      calories than females (2918 +/- 927 and 2304 +/- 713 Kcal/day, respectively; P <
      0.05). Both genders consumed below recommended levels. Carbohydrate, protein, and
      fat accounted for 53%, 19%, and 28% of daily calorie intake, respectively.
      Average daily carbohydrate and protein intake was 5.1 +/- 1.8 and 1.8 +/- 0.6
      g/kg body weight, respectively. Protein intake, but not carbohydrate intake, met
      recommendations. Supplementation significantly increased athletes' energy, total
      carbohydrate, protein, and fat intake. Of 17 micronutrients assessed, intake
      ranged between 120% and 366% of recommended daily intake with food alone and
      between 134% to 680% of recommended daily intake with supplements. CONCLUSIONS:
      Canadian high-performance athletes do not consume adequate energy or
      carbohydrates. However, their intake of micronutrients exceed current recommended
      daily intakes, even when supplements are not considered, indicating that athletes
      make high-quality food choices. Supplementation significantly increased energy,
      macronutrient, and micronutrient intake.

PMID- 19741315
TI  - Fluconazole as a prophylactic measure for tinea gladiatorum in high school
      wrestlers.
AB  - OBJECTIVE: To evaluate the use of prophylactic oral fluconazole in reducing the
      incidence of tinea gladiatorum in high school wrestlers. DESIGN: A prospective
      longitudinal study was conducted on high school wrestlers in northwest Ohio
      between 1997 and 2007. SETTING: Two northwest Ohio high school wrestling teams.
      PARTICIPANTS: High school wrestlers (373). INTERVENTIONS: Prophylactic
      fluconazole at a daily oral dosage of 100 mg for a 3-day regimen prior to the
      onset of the competitive interscholastic wrestling season and 6 weeks into the
      wrestling season. Guardians of participants signed consent forms outlining the
      risks associated with fluconazole prior to being enrolled into the study. MAIN
      OUTCOME MEASURES: Incidence of tinea gladiatorum in participants. RESULTS: Over
      the course of this 10-year study, out of 373 participants using prophylactic
      fluconazole, the incidence rate of tinea gladiatorum dropped from 67.4% to 3.5%.
      It should be noted that more than 50% of these infections occurred within the
      initial year of this study when the second administration of fluconazole was
      given at week 8 instead of week 6. No adverse effects were reported over the 10
      year study period. CONCLUSIONS: The twice-per-season regimen of 100 mg daily for
      3 days was highly effective in dramatically reducing the incidence of these skin
      lesions. The success of our study is 2-fold: First, fluconazole provided
      prophylaxis. Second, the overall incidence of fungal disease throughout the
      entire wrestling team was markedly decreased because most of the wrestlers
      participated in this study, significantly reducing exposure to these lesions
      through wrestling practice. No adverse effects in the use of fluconazole over
      this 10-year study period were reported.

PMID- 19741316
TI  - No dehydration in mountain bike ultra-marathoners.
AB  - OBJECTIVE: To assess the change in body composition and hydration status in
      cyclists in a mountain bike ultra-marathon. DESIGN: Prospective observational
      field study. SETTING: "Swiss Bike Masters" 2008 over 120 km with a total climb of
      5000 m in altitude. PARTICIPANTS: Thirty-seven male mountain bikers.
      INTERVENTIONS: None. MAIN OUTCOME MEASURES: Prerace and postrace, body mass,
      percent body fat, skeletal muscle mass, and selected hematologic and urinary
      parameters were measured to quantify changes in body mass and hydration status.
      Athletes reported their fluid intake during the race. RESULTS: The athletes lost
      1.4 kg in body mass (P < 0.001), equal to 1.9% body mass. Fat mass remained
      stable and skeletal muscle mass decreased by 0.4 kg (P < 0.05). Prerace fat mass
      was correlated to total race time (r = 0.37, P < 0.05). The cyclists drank 6.5
      (1.8) L of fluids during the race corresponding to 0.7 (0.2) L per hour. A
      significant inverse relationship was seen between change in body mass and race
      time when controlled for change in skeletal mass and fluid intake during the race
      (P > 0.05). Plasma sodium decreased by 0.7% (P < 0.05), plasma volume increased
      by 1.4%, and plasma urea increased by 40% (P < 0.05). Urinary-specific gravity
      increased by 0.4% (P < 0.05). The decrease in skeletal muscle mass was associated
      with the increase in plasma urea (r = -0.34; P < 0.05). Fluid intake was
      associated with the change in urinary-specific gravity (r = -0.45; P < 0.01).
      CONCLUSIONS: We conclude that these mountain bike ultra-marathoners suffered a
      significant decrease in body mass and skeletal muscle mass but no dehydration.

PMID- 19741317
TI  - Prevalence of the female athlete triad in high school athletes and sedentary
      students.
AB  - OBJECTIVE: To determine the prevalence of the female athlete triad (low energy
      availability, menstrual dysfunction, and low bone mineral density) in high school
      varsity athletes in a variety of sports compared with sedentary students/control
      subjects. DESIGN: Prospective study. SETTING: Academic medical center in the
      Midwest. PARTICIPANTS: Eighty varsity athletes and 80 sedentary students/control
      subjects volunteered for this study. INTERVENTION: Subjects completed
      questionnaires, had their blood drawn, and underwent bone mineral density
      testing. MAIN OUTCOME MEASURES: Each participant completed screening
      questionnaires assessing eating behavior, menstrual status, and physical
      activity. Each subject completed a 3-day food diary. Serum hormonal, thyroid
      stimulating hormone, and prolactin levels were determined. Bone mineral density
      and body composition were measured by dual-energy x-ray absorptiometry. RESULTS:
      Low energy availability was present in similar numbers of athletes (36%) and
      sedentary/control subjects (39%; P = 0.74). Athletes had more menstrual
      abnormalities (54%) compared with sedentary students/control subjects (21%) (P <
      0.001). Dual-energy x-ray absorptiometry revealed that 16% of the athletes and
      30% of the sedentary/control subjects had low bone mineral density (P = 0.03).
      Risk factors for reduced bone mineral density include sedentary control student,
      low body mass index, and increased caffeine consumption. CONCLUSIONS: A
      substantial number of high school athletes (78%) and a surprising number of
      sedentary students (65%) have 1 or more components of the triad. Given the high
      prevalence of triad characteristics in both groups, education in the formative
      elementary school years has the potential to prevent several of the components in
      both groups, therefore improving health and averting long-term complications.

PMID- 19741318
TI  - Practical management: a systematic approach to the evaluation of exercise-related
      syncope in athletes.
AB  - Syncope and presyncope are relatively common presentations among athletes. The
      distinction between post-exercise and during-exercise syncope is critically
      important. While the great majority of these episodes occur just after exercise
      and are benign, syncope can be an indication of serious underlying cardiovascular
      disease if it occurs during exercise. Syncope presents a challenging differential
      diagnosis, as well as a daunting array of diagnostic tests and advanced imaging
      strategies. Sequencing a proper evaluation, and deciding who requires
      consultation and restriction, can be difficult for the medical provider. We
      present a systematic approach that assists the sports physician in arriving at a
      diagnosis and organizing an initial management strategy.

PMID- 19741319
TI  - Serious morbidity associated with popliteal artery entrapment syndrome.

PMID- 19741320
TI  - The effects of exercise programs on cognition in older adults: a review.

PMID- 19741321
TI  - Effects of regular exercise on the aging immune system: a review.

PMID- 19741322
TI  - Caffeine during exercise improves cognitive and cycling performance.

PMID- 19741323
TI  - Complications after surgery or nonoperative treatment for acute achilles tendon
      rupture.

PMID- 19741324
TI  - Creativity: an organizational schema.
AB  - OBJECTIVE: To describe an organizational schema of human creativity. BACKGROUND:
      Previous research has concluded that creativity involves something novel and
      useful, but whether creativity is common or rare, domain-specific or domain
      general, quantitative or qualitative, or personal or social remains unresolved.
      METHOD: Extant research from neurobiology, psychology, cognitive science, and
      neuroeconomics was used to generate a novel synthesis that explains human
      creative behavior. RESULTS: Creativity is the attempt to bridge the gap between
      what is and what should be. It emerges from the interplay of 5 commonly shared
      factors: motivation, perception, action, temperament, and social interaction. The
      reward value of what exists compared with an imagined possibility generates the
      motivational voltage that drives the creative effort. Action to attain the goal
      requires a dexterously executed plan, and dexterity levels are influenced by both
      practice effects and biologic biases. Temperament sustains the creative effort
      during periods of nonreward in anticipation of goal completion. Societal
      esthetics measure the success of creative efforts. Personal skill sets derived
      from nature and nurture vary between individuals and determine one's own creative
      phenotype. CONCLUSIONS: Despite great qualitative and quantitative differences
      between individuals, the neurobiologic principles of creative behavior are the
      same from the least to the most creative among us.

PMID- 19741325
TI  - Neuropsychologic assessment of a population-based sample of Gulf War veterans.
AB  - OBJECTIVE: The objective of this project was to compare neuropsychologic
      performance and quality of life in a population-based sample of deployed Gulf War
      (GW) veterans with and without multisymptom complaints. BACKGROUND/METHODS: The
      study participants were obtained from the 30,000 member population-based National
      Health Survey of GW-era veterans conducted in 1995. Cases (N=25) were deployed to
      the year 1990 and 1991 GW and met Center for Disease Control and Prevention
      criteria for multisymptom GW illness (GWI). Controls (N=16) were deployed to the
      1990 and 1991 GW but did not meet Center for Disease Control and Prevention
      criteria for GWI. RESULTS: There were no significant differences in composite
      scores on the traditional and computerized neuropsychologic battery (automated
      neuropsychologic assessment metrics) between GW cases and controls using
      bivariate techniques. Multiple linear regression analyses controlling for
      demographic and clinical variables revealed composite automated neuropsychologic
      assessment metrics scores were associated with age (b=-7.8; P=0.084), and
      education (b=22.9; P=0.0012), but not GW case or control status (b=-63.9;
      P=0.22). Compared with controls, GW cases had significantly more impairment on
      the Personality Assessment Inventory and the short form-36. CONCLUSIONS: Compared
      with GW controls, GW cases meeting criteria for GWI had preserved cognition
      function but had significant psychiatric symptoms and lower quality of life.

PMID- 19741326
TI  - Depression impairs executive functioning in Parkinson disease patients with low
      educational level.
AB  - OBJECTIVE: To assess overall cognitive performance and executive functioning of
      nondemented Parkinson disease (PD) patients, and the influence of variables such
      as depression and education on cognition. BACKGROUND: Cognitive dysfunction in PD
      is common even in early stages. Different variables have been identified as
      potential risk factors for cognitive decline in PD. Some of these variables, such
      as depression and educational level, are complexly interrelated. METHODS: Eighty
      two (male:female 52:30) subjects underwent clinical assessment which included the
      Unified Parkinson's Disease Rating Scale, Schwab-England Scale, Hoehn-Yahr Scale,
      Beck Depression Inventory, the Frontal Assessment Battery (FAB), and the Mini
      Mental State Examination (MMSE). RESULTS: Patients with higher education, younger
      age, and who had a younger age at disease onset performed better on both the FAB
      and MMSE. Severity of disease correlated with worse cognitive performance.
      Performance on the FAB, but not the MMSE, worsened with increased severity of
      depressive symptoms. When patients were divided into groups with lower (< or =4 y
      of schooling) and higher (> or =5 y of schooling) education, the FAB and Beck
      Depression Inventory correlated negatively only in the group with lower
      educational level. CONCLUSIONS: Patients with PD present with cognitive
      impairment even when nondemented. Depression may exacerbate executive
      dysfunction, especially in subjects with lower educational level.

PMID- 19741327
TI  - Loss of somatosensory-evoked potentials and the timing of perception.
AB  - OBJECTIVE: To determine if patients with brain lesions who have a unilateral loss
      of their primary somatosensory-evoked potential (SSEP) have altered temporal
      perception. BACKGROUND: Benjamin Libet postulated that the neural processing of
      stimuli to reach the conscious awareness takes 300 to 500 milliseconds and that
      accurate temporal perception of stimulus onset requires a retroactive
      computation. Although Libet proposed that the primary SSEP acts as a timing
      marker for this backward referral of perceived stimulus onset time, there has not
      been a systematic study of the necessity of the primary SSEP for perceptual
      timing. METHODS: Participants were 10 healthy older adults and 10 stroke patients
      with hemisensory deficits. SSEPs were recorded from each hemisphere using median
      nerve stimulation. The participants' temporal perception of sensory stimuli was
      determined by asking them the temporal order of bilateral hand stimuli over
      varying interstimulus intervals. RESULTS: Patients with unilateral loss of SSEPs
      had a significantly greater mean delay in perception of stimuli from their
      contralesional arm than participants with intact bilateral SSEPs [mean delay (+/
      standard deviation): 134 (+/-142) msec vs. 2.5 (+/-13) msec; P=0.03].
      CONCLUSIONS: These results demonstrate that loss of SSEP is associated with a
      delay in perceptual awareness. This observation is consistent with the hypotheses
      that the SSEP acts as a marker for cortical events important for perceptual
      timing.

PMID- 19741328
TI  - Sustained attention deficit along the psychosis proneness continuum: a study on
      the Sustained Attention to Response Task (SART).
AB  - BACKGROUND: Sustained attention deficits have been associated with schizophrenia.
      However, these findings were limited to patients with schizophrenia and cannot be
      generalized to a wider nonclinical sample with schizotypal personality features.
      OBJECTIVES: This study aimed to examine the sensitivity of a theory-driven test,
      the Sustained Attention Response to Task (SART), in individuals with schizotypal
      personality features. We also investigated the relationships between different
      parameters of SART and different dimensions of schizotypal features. METHODS: One
      hundred and ninety-nine participants (74 individuals with schizophrenia, 69
      individuals with psychometrically determined schizotypal features, and 56 healthy
      controls) took part in this study. Participants scoring in the top 10% of the
      Schizotypal Personality Questionnaire (SPQ) score were identified as having
      schizotypal features, and those scoring in the bottom 10% were recruited as
      healthy controls. All participants were administered the SART in an experimental
      cubicle. RESULTS: The findings indicated that: (1) significant differences were
      found in SART commission error and sensitivity between the 3 experimental groups,
      with patients with schizophrenia and individuals with schizotypal features
      performing worse than healthy controls; (2) there was a trend toward statistical
      significance for SART efficiency score and d', with controls performing better
      than patients with schizophrenia and individuals with schizotypal features; (3)
      some associations between some SART indices and schizotypal traits were found;
      and (4) there was no significant relationship between SART indices and clinical
      symptoms in patients with schizophrenia in this study. CONCLUSIONS: : This
      investigation demonstrated the potential value of a relatively new sustained
      attention paradigm for research in schizophrenia spectrum disorders.

PMID- 19741329
TI  - Laterality of pain: modulation by placebo and participants' paranormal belief.
AB  - OBJECTIVE: To investigate the effects of placebo and paranormal belief on the
      laterality of pain perception. BACKGROUND: The right hemisphere is dominantly
      involved in both the mediation of pain sensation and the belief in paranormal
      phenomena. We set out to assess a possible influence of long-term belief systems
      on placebo analgesia in response to unilateral nociceptive stimuli. METHOD: Forty
      healthy participants (20 high and 20 low believers as indexed by the Magical
      Ideation Scale) underwent a placebo analgesia study measuring stimulus detection,
      pain threshold, and pain tolerance by electrostimulation on the right and left
      hand. Placebo treatment consisted of the application of a sham cream on the
      hands. RESULTS: Placebo had a positive influence on pain perception in the 3
      variables. Enhanced pain sensitivity for the left side was only found for the
      disbelievers. Placebo treatment resulted in a double dissociation: in believers,
      it increased tolerance exclusively on the left side, in disbelievers on the right
      side. CONCLUSIONS: Our results confirm laterality effects in pain perception.
      However, only disbelievers conformed to the expected higher left-sided
      sensitivity. Placebo effects were dissociated between believers and disbelievers
      suggesting that short-term reactions to a placebo are modulated by a person's
      long-term belief system.

PMID- 19741330
TI  - Association of cognitive impairment with smoking, alcohol consumption, tea
      consumption, and exercise among Chinese nonagenarians/centenarians.
AB  - PURPOSE: In the present study, we observed the association of cognitive
      impairment with current/former habits of smoking, alcohol consumption, tea
      consumption, and exercise among very old people using a Chinese cohort aged 90 to
      108 years. METHODS: A cross-sectional study. RESULTS: The sample included 681
      unrelated Chinese nonagenarians/centenarians (67.25% women). In men, compared
      with subjects without cognitive impairment, those with cognitive impairment had
      significantly higher prevalence of habits of smoking (P=0.048 and 0.004, for
      former/current, respectively) and alcohol consumption (P=0.003 and 0.049, for
      former/current, respectively) but had significantly lower prevalence of habits of
      tea consumption (P=0.041 and 0.044, for former/current, respectively) and current
      exercise (P=0.020). Subjects with habits of smoking had significantly lower
      cognitive function scores than those without these habits (mean difference=1.78
      and 1.69, P=0.029 and 0.035, for former/current, respectively), but subjects with
      habit of current exercise had significantly higher cognitive function scores than
      those without this habit (mean difference=1.53, P=0.038). However, in women,
      there were no significant differences in prevalence of these habits between
      subjects with and without cognitive impairment and also no significant
      differences in cognitive function scores between subjects with and without these
      habits. Only current smoking habits in men had a significant odds ratio for
      cognitive impairment (odds ratio, 2.125; 95% confidence interval, 1.186-3.998).
      CONCLUSIONS: Among nonagenarians/centenarians, in men, there are associations of
      cognitive impairment with habits of former/current smoking and current exercise,
      as well as indefinite associations with habits of alcohol and tea consumption.
      Smoking may have a significant negative impact on cognitive function, but current
      exercise significantly improve cognitive function. However, in women, there are
      no associations of cognitive impairment with all the habits.

PMID- 19741331
TI  - Hashimoto encephalopathy presenting as schizophrenia-like disorder.
AB  - OBJECTIVE: Hashimoto encephalopathy (HE) is associated with numerous
      neuropsychiatric symptoms and responds well to steroid therapy. In the past, only
      a few cases were reported to present with pure psychiatric syndromes. We describe
      a case of HE with presenting symptoms like that of schizophrenic patients.
      METHODS: We describe a 73-year-old woman with a history of autoimmune
      thyroiditis. She had psychotic symptoms for 3 years that responded poorly to
      antipsychotic agents, and she was thus admitted in 2007. RESULTS: The diagnosis
      of HE was made, although the patient presented neurologic symptoms and signs
      including abnormal electroencephalography, recent memory impairment, and
      executive function declination. The psychotic symptoms subsided completely in a
      few days after high-dose intravenous steroid therapy. CONCLUSIONS: The
      neuropsychiatric manifestation of HE can be similar to typical schizophrenia.
      Considering the effectiveness of steroid therapy for HE, we suggested HE as an
      important differential diagnosis for psychotic disorders, particularly for those
      patients of late onset, with abnormal electroencephalography, history of
      autoimmune thyroiditis, or poor response to conventional psychiatric treatment,
      so as to provide prompt and effective treatment for these patients.

PMID- 19741333
TI  - Current Opinion in Critical Care. Current world literature.

PMID- 19741335
TI  - Current world literature.

PMID- 19741336
TI  - Shifting to new targets in pharmacological prevention of cardiovascular diseases.

PMID- 19741338
TI  - Cyclooxygenase and prostaglandin synthases: roles in plaque stability and
      instability in humans.
AB  - PURPOSE OF REVIEW: Cyclooxygenase (COX) is the key enzyme of the arachidonic acid
      metabolism and it plays a major role in development of both coronary and
      cerebrovascular disease. In this review, we will analyze the role of COX and
      prostaglandin synthases in plaque stability. RECENT FINDINGS: As shown by
      experimental studies based on biochemical measurement of eicosanoid biosynthesis
      and by the results of clinical trials, COX plays a key role in plaque evolution.
      Two COX-isozymes have been identified, COX-1 and COX-2, with different tissue
      distribution, substrate specificity, regulatory mechanism and susceptibility to
      drugs inhibition. Whereas, the role of platelet COX-1 in acute coronary syndrome
      and ischemic stroke is definitely established through several large clinical
      studies with aspirin, the role of COX-2 in these settings is still under
      investigation because this enzyme was characterized only recently and its
      inhibitors (coxibs) became available only in 1998. Recent findings seem to
      suggest that functional consequences of COX-2 expression and inhibition in
      different clinical settings may depend on different expression of upstream and
      downstream receptors as well as by genetic polymorphism. SUMMARY: COX-2 and
      prostaglandin synthases and their modulation play a major role in plaque
      homeostasis and in its clinical manifestations.

PMID- 19741337
TI  - Macrophage heterogeneity in atherosclerotic plaques.
AB  - PURPOSE OF REVIEW: The varied behaviour of macrophages and foam cells during
      atherosclerosis and its clinical sequelae prompt the question whether all these
      activities can be the property of a single cell population. RECENT FINDINGS:
      Subsets of monocytes with distinct patterns of surface markers and behaviours
      during inflammation have recently been characterized and shown to have
      complementary roles during progression of atherosclerosis. A variety of
      macrophage phenotypes derived from these monocyte subsets in response to
      mediators of innate and acquired immunity have also been found in plaques. Based
      on functional properties and genomic signatures, they may have different impacts
      on facets of plaque development, including fibrous cap and lipid core formation.
      SUMMARY: Monocyte and macrophage phenotypic diversity is important in
      atherogenesis. More work is needed to define consistent marker sets for the
      different foam cell phenotypes in experimental animals and humans. Cell tracking
      studies are needed to establish their relationship with monocyte subtypes. In
      addition, genetic and pharmacological manipulation of phenotypes will be useful
      to define their functions and exploit the resulting therapeutic potential.

PMID- 19741339
TI  - Lipid metabolism and causal pathways for cardiovascular disease in chronic kidney
      disease.

PMID- 19741340
TI  - Dietary patterns: time to simplify the message until we can clarify the
      specifics.

PMID- 19741341
TI  - A matter of judgement: clinical guidelines and scientific reductionism.

PMID- 19741342
TI  - Atherosclerosis risk factors can impose aberrant DNA methylation patterns: a tale
      of traffic and homocysteine.

PMID- 19741343
TI  - Therapy and clinical trials: Familial hypercholesterolaemia and prevention of
      coronary artery disease.

PMID- 19741344
TI  - This month's American College of Sports Medicine's (ACSM) Clinician Profile:
      James L. Moeller.

PMID- 19741345
TI  - Iron and irony.

PMID- 19741347
TI  - Prevention of noncontact ACL injuries in women: use of the core of evidence to
      clip the wings of a "Black Swan".

PMID- 19741348
TI  - Ten-year-old boy with a recurrent knee effusion.

PMID- 19741349
TI  - Management of ankle syndesmosis injuries in the athlete.
AB  - Syndesmotic injuries or high ankle sprains in athletes can occur in elite and
      recreational athletes. They typically require a longer recovery and a significant
      delay in return to play compared with routine ankle sprains. Avoiding a
      misdiagnosis is important and is dependent on being aware of the mechanism of
      injury, a thorough physical examination, and careful interpretation of imaging
      studies. Management is guided by the severity of injury and the demands of the
      athlete. Many mild or stable injuries can be treated nonoperatively; however,
      acute surgical repair or stabilization in high-grade injuries can provide
      excellent results and an earlier return to play in selected cases.

PMID- 19741350
TI  - Clinical and imaging assessment for superior labrum anterior and posterior
      lesions.
AB  - In the evaluation of the painful shoulder, especially in the overhead athlete,
      diagnosing superior labrum anterior and posterior (SLAP) lesions continues to
      challenge the clinician because of 1) the lack of specificity of examination
      tests for SLAP; 2) a paucity of well-controlled studies of those tests; and 3)
      the presence of coexisting confounding abnormalities. Some evidence indicates
      that multiple positive tests increase the likelihood that a SLAP lesion is
      present, but no one physical examination finding conclusively makes that
      diagnosis. The goals of this article were to review the physical examination
      techniques for making the diagnosis of SLAP lesions, to evaluate the clinical
      usefulness of those examinations, and to review the role of magnetic resonance
      imaging in making the diagnosis.

PMID- 19741351
TI  - Diagnosis and management of thoracic outlet syndrome.
AB  - Thoracic outlet syndrome (TOS) results from compression of the neurovascular
      structures that pass through the thoracic outlet. TOS may be classified as
      neurogenic TOS (NTOS), venous TOS (VTOS), or arterial TOS (ATOS). NTOS presents
      with upper-extremity symptoms attributable to compression of the brachial plexus.
      VTOS, also known as Paget-Schroetter Syndrome, involves subclavian-axillary
      venous occlusion, thrombus formation, and rare embolization. ATOS results from
      obstruction of the subclavian artery with claudication, thrombus formation, and
      possible embolization. Adjunct diagnostic studies frequently confirm the
      diagnoses of VTOS and ATOS, but not of NTOS. Successful TOS treatment depends on
      the establishment of an accurate diagnosis and identification of causative
      factors. NTOS should be treated initially with physical therapy, but may require
      surgical decompression, including first rib excision and scalenectomy. VTOS
      usually requires urgent thrombolysis, anticoagulation, and surgical
      decompression. The treatment of ATOS is directed at restoring arterial blood flow
      in addition to surgical decompression.

PMID- 19741352
TI  - Prevention of elbow injuries in youth baseball pitchers.
AB  - There is concern among sports medicine practitioners that the number of youth
      baseball pitchers with elbow injuries appears to be increasing. Research points
      to overuse as the principle risk factor. The risk of elbow pain in youth pitchers
      is correlated with the number of pitches thrown in a game and in a season.
      Adolescents who competitively pitch more than 85 pitches per game, more than 8
      months out of a year, or with arm fatigue are several times more likely to
      require elbow surgery. Poor pitching mechanics also appear to contribute to
      injury risk. Existing research does not show a significant correlation between
      curveballs and injury. Adults should help youth pitchers avoid fatigue, overuse,
      and improper mechanics. If elbow pain develops, the youth pitcher should be
      evaluated by a sports medicine physician.

PMID- 19741353
TI  - Injuries and medical issues in synchronized Olympic sports.
AB  - Spectators of the Olympic Games can enjoy a wide variety of sports, including
      strength, team, timed, endurance, and artistic sports. In the Olympic program,
      there are two synchronized events: synchronized diving and synchronized swimming.
      The precision of the synchronization of the athlete's movements and skills is an
      added feature of entertainment. Synchronized athletes have additional training
      requirements to perfect the synchronization of their skills. The physical demands
      on the athlete from the repetition of training required for the perfection of
      synchronization result in injuries unique to these sports. Although both
      traumatic and overuse injuries occur, overuse injuries are more common. As these
      disciplines are artistic, judged sports, these athletes also are susceptible to
      eating disorders and the female athlete triad. This article reviews the training
      regimen of these athletes and outlines the injuries and health concerns that are
      common in the synchronized sports.

PMID- 19741354
TI  - Foot and ankle injuries in the barefoot sports.
AB  - Playing sports barefoot has been contested since the very beginnings of athletic
      competition. Even today, some data suggest that shoes may limit the adaptive
      pronation that occurs after footstrike during running gait. This pronation likely
      protects runners from injury. Boardsport participants who perform their sports
      barefoot on the water seem to be at risk for foot and ankle injuries. The high
      impact forces in gymnastics place participants at risk for foot and ankle
      injuries, as well. Swimming and diving have a low rate of foot and ankle
      injuries. The risk of ankle sprain in beach volleyball, which is played barefoot,
      seems to be lower than that for indoor volleyball, played wearing shoes. Martial
      arts place competitors at risk for injuries to the foot and ankle from torsional
      and impact mechanisms. Athletes who hope to return to barefoot competition after
      injury should perform their rehabilitation in their bare feet.

PMID- 19741355
TI  - Field hockey injuries.
AB  - Field hockey is a popular sport that is played throughout the world. Most of the
      literature on the sport has focused on describing injury patterns. This research
      reveals that most injuries are minor and that the most common injury is an ankle
      sprain. Studies also suggest that men have a higher rate of injury and that they
      experience severe injuries more often than women. These severe injuries include
      trauma to the head, face, and upper limb and usually are the result of contact
      with the stick or ball. Consequently, many authors suggest that all players wear
      face and hand protection. Current International Field Hockey Federation rules
      recommend minimal protective equipment (e.g., mouthguard, shin, and ankle
      guards), and surveys indicate that many players do not wear mouthguards
      regularly. Looking into the future, research should focus on developing and
      evaluating effective strategies for injury prevention.

PMID- 19741356
TI  - The reemergence of the trampoline as a recreational activity and competitive
      sport.
AB  - The recreational use of trampolines is widespread and growing rapidly around the
      world. The reported incidence of significant injuries continues to increase
      despite more than three decades of attempts to educate the public on the inherent
      dangers of trampolines and appropriate safety rules for their use. Competitive
      trampolining also is growing, although there is scant medical literature related
      to training issues and injuries to assist the physician in guiding and treating
      these athletes. It is anticipated that with the increased use of trampolines and
      with the evolution of ever more complex competitive techniques and routines, the
      potential for catastrophic injuries in competition will increase. This article
      discusses awareness of the risks and attempts to mitigate injuries. It remains
      unclear, from an injury risk standpoint, whether trampolines can be used with an
      acceptable degree of safety.

PMID- 19741357
TI  - Radrue method for reconstruction of external photon doses for Chernobyl
      liquidators in epidemiological studies.
AB  - Between 1986 and 1990, several hundred thousand workers, called "liquidators" or
      "clean-up workers," took part in decontamination and recovery activities within
      the 30-km zone around the Chernobyl nuclear power plant in Ukraine, where a major
      accident occurred in April 1986. The Chernobyl liquidators were mainly exposed to
      external ionizing radiation levels that depended primarily on their work
      locations and the time after the accident when the work was performed. Because
      individual doses were often monitored inadequately or were not monitored at all
      for the majority of liquidators, a new method of photon (i.e., gamma and x rays)
      dose assessment, called "RADRUE" (Realistic Analytical Dose Reconstruction with
      Uncertainty Estimation), was developed to obtain unbiased and reasonably accurate
      estimates for use in three epidemiologic studies of hematological malignancies
      and thyroid cancer among liquidators. The RADRUE program implements a time-and
      motion dose-reconstruction method that is flexible and conceptually easy to
      understand. It includes a large exposure rate database and interpolation and
      extrapolation techniques to calculate exposure rates at places where liquidators
      lived and worked within approximately 70 km of the destroyed reactor. The RADRUE
      technique relies on data collected from subjects' interviews conducted by trained
      interviewers, and on expert dosimetrists to interpret the information and provide
      supplementary information, when necessary, based upon their own Chernobyl
      experience. The RADRUE technique was used to estimate doses from external
      irradiation, as well as uncertainties, to the bone marrow for 929 subjects and to
      the thyroid gland for 530 subjects enrolled in epidemiologic studies. Individual
      bone marrow dose estimates were found to range from less than one muGy to 3,300
      mGy, with an arithmetic mean of 71 mGy. Individual thyroid dose estimates were
      lower and ranged from 20 muGy to 507 mGy, with an arithmetic mean of 29 mGy. The
      uncertainties, expressed in terms of geometric standard deviations, ranged from
      1.1 to 5.8, with an arithmetic mean of 1.9.

PMID- 19741358
TI  - Calculation of indoor effective dose factors in ORNL phantoms series due to
      natural radioactivity in building materials.
AB  - In this paper the effective dose in the age-dependent ORNL phantoms series, due
      to naturally occurring radionuclides in building materials, was calculated. The
      absorbed doses for various organs or human tissues have been calculated. The MCNP
      4B computer code was used for this purpose. The effective dose was calculated
      according to ICRP Publication 74. The obtained values of dose conversion factors
      for a standard room are: 1.033, 0.752 and 0.0538 nSv h-1 per Bq kg-1 for elements
      of the U and Th decay series and for the K isotope, respectively. The values of
      effective dose agreed generally with those found in the literature, although the
      values estimated here for elements of the U series were higher in some cases.

PMID- 19741359
TI  - Assessment of organ absorbed doses and estimation of effective doses from
      pediatric anthropomorphic phantom measurements for multi-detector row CT with and
      without automatic exposure control.
AB  - This study was designed to measure organ absorbed doses from multi-detector row
      computed tomography (MDCT) on pediatric anthropomorphic phantoms, calculate the
      corresponding effective doses, and assess the influence of automatic exposure
      control (AEC) in terms of organ dose variations. Four anthropomorphic phantoms
      (phantoms represent the equivalent of a newborn, 1-, 5-, and 10-y-old child) were
      scanned with a four-channel MDCT coupled with a z-axis-based AEC system. Two CT
      torso protocols were compared: a first protocol without AEC and constant tube
      current-time product and a second protocol with AEC using age-adjusted noise
      indices. Organ absorbed doses were monitored by thermoluminescent dosimeters
      (LiF: Mg, Cu, P). Effective doses were calculated according to the tissue
      weighting factors of the International Commission on Radiological Protection ().
      For fixed mA acquisitions, organ doses normalized to the volume CT dose index in
      a 16-cm head phantom (CTDIvol16) ranged from 0.6 to 1.5 and effective doses
      ranged from 8.4 to 13.5 mSv. For the newborn-equivalent phantom, the AEC
      modulated scan showed almost no significant dose variation compared to the fixed
      mA scan. For the 1-, 5- and 10-y equivalent phantoms, the use of AEC induced a
      significant dose decrease on chest organs (ranging from 61 to 31% for thyroid, 37
      to 21% for lung, 34 to 17% for esophagus, and 39 to 10% for breast). However, AEC
      also induced a significant dose increase (ranging from 28 to 48% for salivary
      glands, 22 to 51% for bladder, and 24 to 70% for ovaries) related to the high
      density of skull base and pelvic bones. These dose increases should be considered
      before using AEC as a dose optimization tool in children.

PMID- 19741360
TI  - Intake risk and dose evaluation methods for workers in radiochemistry labs of a
      medical cyclotron facility.
AB  - The aim of this paper is to evaluate the risks and doses for the internal
      contamination of the radiochemistry staff in a high workload medical cyclotron
      facility. The doses from internal contamination derive from the inhalation of
      radioactive gas leakage from the cells by personnel involved in the synthesis
      processes and are calculated from urine sample measurements. Various models are
      considered for the calculation of the effective committed dose from the analysis
      of these urine samples, and the results are compared with data obtained from
      local environmental measurement of the radioactivity released inside the lab.

PMID- 19741361
TI  - Experimental and theoretical study of radon distribution in soil.
AB  - Radon concentration as a function of the soil depth (0-2.6 m) was measured during
      the years 2002-2003 and 2003-2004 on the Aristotle University campus. Radium
      distribution in soil was found constant. On the contrary, as expected, radon
      concentration increased with soil depth. However, the radon concentration did not
      follow the well known monotonous increase, which levels off to a saturation
      value. In both radon distributions, radon concentration increased up to a soil
      depth of about 80 cm, seemed to remain constant at depths of 80-130 cm, and then
      increased again. The experimental distribution was reproduced by solving the
      general transport equation (diffusion and advection). The main finding of the
      numerical investigation is that the aforementioned, experimentally observed,
      profile of radon concentration can be explained theoretically by the existence of
      two soil layers with different diffusion-advection characteristics. Soil sample
      analysis verified the existence of two different soil layers. Different boundary
      conditions of the radon concentration at the soil surface were used for the
      solution of the diffusion-advection equation. It was found that the calculated
      radon concentration in the soil is, away from the soil surface, the same for the
      two boundary conditions used. However, from the (frequently used) boundary
      condition of zero radon concentration at the soil surface, the experimental
      profile of the radon concentration at the soil surface cannot be deduced. On the
      contrary, with more appropriate boundary conditions the radon concentration at
      the soil surface could be deduced from the experimental profile. The equivalent
      diffusion coefficient could be uncovered from the experimental profile, which can
      then be used to estimate the radon current, which is important, for example, for
      the estimation of radon entrance to dwellings.

PMID- 19741362
TI  - Residential magnetic fields and measures of neutral-to-earth voltage: variability
      within and between residences.
AB  - The objectives of this study were to characterize temporal patterns of magnetic
      fields (Bavg) and two measures of neutral-to-earth voltage: the voltage between
      the water line and earth (VW-E), and the voltage between bathtub plumbing
      fixtures and the drain (Vbath). The latter is a source of exposure to contact
      current in bathing children that has been proposed to explain the reported
      association between power-frequency magnetic fields and childhood leukemia. These
      quantities were measured each minute in a sample of 15 single-detached residences
      in San Jose, CA. Generally, Bavg, VW-E, and Vbath were positively correlated with
      each other within residences, and displayed similar diurnal patterns. Weekday and
      weekend patterns displayed qualitative differences that reflect the more
      scheduled workday for weekdays, and a less structured pattern for weekends. When
      pooled with two prior measurement studies, positive associations across
      residences between Bavg and both VW-E and Vbath were observed. Home designs over
      the past 30-40 years have lead to a decreasing prevalence of Vbath as conductive
      drains have been swapped out for non-conductive materials. Nonetheless, the
      observed relationships within and across residences indicate that contact current
      has the characteristics of a factor that could explain the association of
      magnetic fields with childhood leukemia.

PMID- 19741363
TI  - Radon and leukemia in the Danish study: another source of dose.
AB  - An epidemiologic study of childhood leukemia in Denmark (2,400 cases; 6,697
      controls) from 1968 to 1994 suggested a weak, but statistically significant,
      association of residential radon exposure and acute childhood lymphoblastic
      leukemia (ALL). The Danish study estimated a relative risk (RR) = 1.56 (95% CI,
      1.05-2.30) for a cumulative exposure of 1,000 Bq m-3 y. For an exposure duration
      of 10 y their RR corresponds to a radon concentration of 100 Bq m-3. There are
      two dose pathways of interest where alpha particles could damage potential stem
      cells for ALL. One is the alpha dose to bone marrow, and two is the dose to
      bronchial mucosa where an abundance of circulating lymphocytes is found. Compared
      with an exposure of about 1 mSv y-1 from natural external background, radon and
      decay products contribute an additional 10 to 60% to the bone marrow equivalent
      dose. The other pathway for exposure of T (or B) lymphocytes is within the
      tracheobronchial epithelium (BE). Inhaled radon decay products deposit on the
      relatively small area of airway surfaces and deliver a significant dose to the
      nearby basal or mucous cells implicated in human lung cancer. Lymphocytes are co
      located with basal cells and are half as abundant. Using a 10-y exposure to 100
      Bq m-3, our dose estimates suggest that the equivalent dose to these lymphocytes
      could approach 1 Sv. The relatively high dose estimate to lymphocytes circulating
      through the BE, potential precursor cells for ALL, provides a dose pathway for an
      association.

PMID- 19741364
TI  - COMAR technical information statement: expert reviews on potential health effects
      of radiofrequency electromagnetic fields and comments on the bioinitiative
      report.
AB  - The Committee on Man and Radiation (COMAR) is a technical committee of the
      Engineering in Medicine and Biology Society (EMBS) of the Institute of Electrical
      and Electronics Engineers (IEEE). Its primary area of interest is biological
      effects of non-ionizing electromagnetic radiation, including radiofrequency (RF)
      energy. The public interest in possible health effects attributed to RF energy,
      such as emitted by mobile phones, wireless telephone base stations, TV and radio
      broadcasting facilities, Wi-Fi systems and many other sources, has been
      accompanied by commentary in the media that varies considerably in reliability
      and usefulness for their audience. The focus of this COMAR Technical Information
      Statement is to identify quality sources of scientific information on potential
      health risks from exposure to RF energy. This Statement provides readers with
      references to expert reports and other reliable sources of information about this
      topic, most of which are available on the Internet. This report summarizes the
      conclusions from several major reports and comments on the markedly different
      conclusions in the BioInitiative Report (abbreviated BIR below). Since appearing
      on the Internet in August 2007, the BIR has received much media attention but,
      more recently, has been criticized by several health organizations (see Section
      titled "Views of health agencies about BIR"). COMAR concludes that the weight of
      scientific evidence in the RF bioeffects literature does not support the safety
      limits recommended by the BioInitiative group. For this reason, COMAR recommends
      that public health officials continue to base their policies on RF safety limits
      recommended by established and sanctioned international organizations such as the
      Institute of Electrical and Electronics Engineers International Committee on
      Electromagnetic Safety and the International Commission on Non-Ionizing Radiation
      Protection, which is formally related to the World Health Organization.

PMID- 19741370
TI  - Is health and productivity an issue for all employers?

PMID- 19741371
TI  - Use of tabletop exercise in industrial training disaster.

PMID- 19741372
TI  - High-pressure injection injury in a furniture repairman--an outwardly minor
      injury with the potential for a devastating outcome.
AB  - The Occupational Medicine Forum is prepared by the ACOEM Occupational and
      Environmental Medical Practice Committee and does not necessarily represent an
      official ACOEM position. The Forum is intended for health professionals and is
      not intended to provide medical or legal advice, including illness prevention,
      diagnosis or treatment, or regulatory compliance. Such advice should be obtained
      directly from a physician and/or attorney. Inquiries and contributions to the
      Forum should be forwarded to Joseph J. Schwerha, MD, MPH by e-mail at
      schwer@pitt.edu.

PMID- 19741375
TI  - Degloving injury of an extremity. Is primary closure obsolete?

PMID- 19741376
TI  - Osteochondritis dissecans of the glenoid: a rare injury secondary to repetitive
      microtrauma.

PMID- 19741377
TI  - Delayed shock after minor blunt trauma due to myocarditis caused by occult giant
      pheochromocytoma.

PMID- 19741378
TI  - Inferior vena cava pseudoaneurysm after penetrating injury of the abdomen: a case
      report.
AB  - Reports of inferior vena cava (IVC) pseudoaneurysms are always associated with
      arteriovenous fistulae and arterial injuries. This seems to be the first case
      report of an isolated IVC pseudoaneurysm in a 40-year-old man who suffered a
      penetrating abdominal injury 4 weeks before being referred to our hospital.
      Jaundice was the finding that leads to the identification of this aneurysm and
      its later successful surgical treatment. This is a nonreported lesion in the
      published literature about IVC injuries, in which the endovascular therapy is
      recently included.

PMID- 19741379
TI  - Penetrating vertebral artery pseudoaneurysm: a novel endovascular stent graft
      treatment with artery preservation.

PMID- 19741380
TI  - Think different: presidential address at the 2009 Eastern Association for the
      Surgery of Trauma.

PMID- 19741381
TI  - Enhancing patient safety in the trauma/surgical intensive care unit.
AB  - BACKGROUND: Preventable deaths due to errors in trauma patients with otherwise
      survivable injuries account for up to 10% of fatalities in Level I trauma
      centers, 50% of these errors occur in the intensive care unit (ICU). The root
      cause of 67% of the Joint Commission sentinel events is communication errors. The
      objective is (1) to study how critical information degrades and how it is lost
      over 24 hours and (2) to determine whether a structured checklist for ICU
      handoffs prevents information loss. METHODS: Prospective cohort study of trauma
      and surgical ICU teams observed with and without use of the checklist. An
      observational period (control group) was followed by a didactic session on the
      science and use of a checklist (study group), which was used for patient
      management and handoffs. Information was tracked for a 24-hour period and all
      handoffs. Comparisons use chi or Fisher's exact test and a p value <0.05 was
      defined as significant. RESULTS: Three hundred and thirty-two patient ICU days
      were observed (119 control, 213 study) and 689 patient care items (303 control,
      386 study) were followed. Seventy-five (10.9%) items were lost over 24 hours; 61
      of 303 (20.1%) without checklist and 14 of 386 (3.6%) with checklist (p <
      0.0001). Critical laboratory values and test results were the most frequent lost
      items (36.1% control vs. 4.5% study p < 0.0001). Six of 75 (8.1%) items were
      correctly ordered but not carried out by ICU nursing staff--all caught and
      corrected with checklist use. CONCLUSION: Critical information is degraded over
      24 hours in the ICU. A structured checklist significantly reduces patient errors
      due to lost information and communication lapses between trauma ICU team members
      at handoffs of care.

PMID- 19741382
TI  - Heart rate variability as a triage tool in patients with trauma during
      prehospital helicopter transport.
AB  - BACKGROUND: Prehospital triage of patients with trauma is routinely challenging,
      but more so in mass casualty situations and military operations. The purpose of
      this study was to prospectively test whether heart rate variability (HRV) could
      be used as a triage tool during helicopter transport of civilian patients with
      trauma. METHODS: After institutional review board approval and waiver of informed
      consent, 75 patients with trauma requiring prehospital helicopter transport to
      our level I center (from December 2007 to November 2008) were prospectively
      instrumented with a 2-Channel SEER Light recorder (GE Healthcare, Milwaukee, WI).
      HRV was analyzed with a Mars Holter monitor system and proprietary software. SDNN
      (standard deviation [SD] of the normal-to-normal R-R interval), as an index of
      HRV, was correlated with prehospital trauma triage criteria, base deficit,
      seriousness of injury, operative interventions, outcome, and other data extracted
      from the patients' medical records. There were no interventions or medical
      decisions based on HRV. Data were excluded only if there was measurement artifact
      or technical problems with the recordings. RESULTS: The demographics were mean
      age 47 years, 63% men, 88% blunt, 25% traumatic brain injury, 9% mortality.
      Prehospital SDNN predicted patients with base excess < or = -6, those defined as
      seriously injured and benefiting from trauma center care, as well as patients
      requiring a life-saving procedure in the operating room. No other available data,
      including prehospital en-route vital signs, predicted any of these. The
      sensitivity, specificity, positive predictive value, and negative predictive
      value were 80%, 75%, 33%, 96%, respectively, with and an overall accuracy of 76%
      for predicting a life-saving intervention in the operating room. CONCLUSIONS:
      This is the first demonstration that prehospital HRV (specifically SDNN) predicts
      base excess and operating room life-saving opportunities. HRV triages and
      discriminates severely injured patients better than routine trauma criteria or en
      route prehospital vital signs. HRV may be a useful civilian or military triage
      tool to avoid unnecessary helicopter evacuation for minimally injured patients. A
      prospective, randomized trial in a larger patient population is indicated.

PMID- 19741383
TI  - Tissue oxygenation monitoring in the field: a new EMS vital sign.
AB  - BACKGROUND: A tissue hemoglobin oxygen saturation (STO2) monitor was created to
      assess the perfusion status of a peripheral muscle bed using near infrared light
      to directly measure oxygen saturation in the microcirculation. Hypoperfusion has
      been noted when the STO2 is <75%. The use of this technology has not been tested
      in the prehospital setting. This pilot study was performed to assess the
      technology's ease of use in the field and to correlate STO2 readings with patient
      outcomes. METHODS: Hospital-based transport vehicles were equipped with STO2
      monitors and personnel were asked to evaluate the functionality of the
      technology. Initial, average, and minimal STO2 values were collected and compared
      with data of the trauma registry. RESULTS: Forty five of 55 surveys were returned
      with 100% reporting ease of use and no reports of interference with monitors or
      avionics. Monitoring length averaged 16.9 minutes +/- 6.9 minutes. Forty-one
      patients had complete data sets and five deaths were reported for a mortality
      rate of 12%. STO2 endpoints revealed and increased risk of death for every 10%
      decrease in STO2. CONCLUSION: The STO2 monitor can easily be used in the
      prehospital environment. In addition, initial recordings were significantly
      different between survivors and nonsurvivors with every 10% decrease in STO2
      increasing mortality threefold. This monitor seems to give the prehospital
      provider a noninvasive tool for assessment of hypoperfusion in the field and may
      allow for earlier resuscitative efforts to commence.

PMID- 19741384
TI  - Elevated serum pancreatic enzyme levels after hemorrhagic shock predict organ
      failure and death.
AB  - BACKGROUND: Intraluminal pancreatic enzymes have been shown in animal models to
      be associated with multiple organ failure after hemorrhagic shock, independent of
      pancreatitis. The translocation of these enzymes into the circulation may serve
      as a marker of hemorrhagic shock-induced gut ischemia in critically injured
      trauma patients. We hypothesized that serum amylase and lipase would be
      significantly elevated in patients presenting in hemorrhagic shock and in those
      who develop organ failure. METHODS: : Review of a prospective database at a level
      1 trauma center from 2000 to 2005. Two thousand seven hundred eleven critically
      injured trauma patients without pancreatic injuries were evaluated for shock
      (systolic pressure <90 mm Hg in the emergency department), massive transfusion
      (10 units of packed red blood cells within the first 24 hours), and organ failure
      (standard criteria for acute pulmonary, cardiovascular, renal, and hepatic system
      failure were used). Serum levels >2 times the upper limit of normal for amylase
      (30-130 U/L) and lipase (7-60 U/L) were defined as elevated. Univariate analyses
      were performed with the Pearson's chi, and binary logistic regression was used to
      determine significant risk factors for organ failure. Results with a p value
      <0.05 were considered significant and are reported. RESULTS: : Patients with
      elevated amylase (n = 481, 18%) were more likely to present in shock (16% vs.
      8%), require massive transfusion (19% vs. 9%), develop organ failure (34% vs.
      16%), and die (23% vs. 13%). Patients with elevated lipase (n = 288, 11%) were
      more likely to require massive transfusion (18% vs. 10%) and develop organ
      failure (43% vs. 16%). Independent predictors of organ failure were age (odds
      ratio [OR] = 1.016), Injury Severity Score (OR = 1.02), massive transfusion (OR =
      3.1), elevated amylase (OR = 1.9), and elevated lipase (OR = 3.2). Elevated
      amylase was also an independent predictor of mortality (OR = 1.3). CONCLUSIONS: :
      Serum levels of pancreatic enzymes are elevated in patients who present in shock
      or require a massive transfusion and are independent predictors of organ failure.
      Whether these elevations are caused by ischemic pancreatitis or the translocation
      of intraluminal enteric pancreatic enzymes is uncertain and future studies are
      needed. Trauma patients with elevated pancreatic enzymes in the absence of a
      pancreatic injury have an increased risk of morbidity and mortality.

PMID- 19741385
TI  - Determination of efficacy of new hemostatic dressings in a model of extremity
      arterial hemorrhage in swine.
AB  - BACKGROUND: The HemCon (HC) bandage and QuickClot have been used over the past 6
      years for treating external compressible hemorrhage in combat casualties.
      Previously, we tested three new hemostatic agents in granular/powder forms that
      were superior to these products. In this study, four new dressings (preselected)
      that are more suitable for battlefield application were evaluated. The efficacy
      and acute safety of the dressings were tested in our standard arterial hemorrhage
      model. METHODS: Anesthetized pigs (n = 38, 37 kg) were instrumented, and arterial
      blood was collected for hematological and coagulation assays. After splenectomy,
      the right femoral artery was isolated, injured (6 mm arteriotomy), and
      unrestricted bleeding allowed for 45 seconds. A hemostatic dressing (HC RTS [n =
      6], Celox-D [CXb, n = 6], TraumaStat [TS, n = 10], Combat Gauze [CG, n = 10], or
      placebo gauze [PG, n = 6]) was then applied over the wound randomly and
      compressed for 2 minutes. Fluid resuscitation was administered and titrated to
      maintain a mean arterial pressure of 65 mm Hg. Animals were observed for 180
      minutes or until death. Computed tomography angiography was performed on
      survivors and tissues were collected for histology. RESULTS: No differences were
      found in baseline blood measures, pretreatment blood loss or fluid infusion among
      groups. HCs and CXb testing discontinued after six unsuccessful tests, and the
      data were excluded. Stable hemostasis was achieved in two PG, two TS, and eight
      CG pigs in remaining groups resulting in stabilized mean arterial pressure and
      significantly different survival rates (20-80%, p = 0.03). CG secured hemostasis
      for 134.6 minutes +/- 22.2 minutes, which was significantly longer than TS (35.7
      +/- 22.0 minutes, p < 0.05) but not different from PG (57.9 +/- 36.2 minutes).
      The average survival time of CG-treated animals (167.3 +/- 5.9 minutes) was also
      significantly longer (p < 0.05) than that of TS- (90.0 +/- 15.3 minutes) or PG
      treated (121 +/- 19.3 minutes) pigs. Posttreatment blood loss was less in CG
      (37.4 +/- 17.3 mL/kg) than that of the two other groups (TS = 79.8 +/- 13.8 mL/kg
      and PG = 75.5 +/- 23.8 mL/kg), but this difference was not significant. No
      significant rise in wound temperature (>1 degrees C) was recorded after treatment
      with dressings and computed tomography images showed no flow through the vessels.
      Histologic observations showed mild to moderate changes in treated vessels with
      no difference between CG and PG. In vitro analysis of blood treated with CG or PG
      (lesser extent) showed increased clotting rate and clot strength. TS treatment
      had no effect on blood clotting activity. CONCLUSION: CG was the most effective
      dressing tested in this arterial hemorrhage model. The hemostatic property of CG
      is attributed to its raw material (nonwoven Rayon and polyester blend), kaolin
      coating, and the large surface area (3 inch x 4 yd) of this absorbent sponge. CG
      is now recommended as the first line of treatment for life-threatening hemorrhage
      on the battlefield, replacing HC.

PMID- 19741386
TI  - Vasopressin attenuates TNF-mediated inflammation in the rat cremaster
      microcirculation.
AB  - BACKGROUND: Our previous study in a swine polytrauma model suggested that
      equieffective systemic pressor doses of arginine vasopressin (AVP) versus
      phenylephrine (PE) have differential effects on the systemic and cerebral
      microcirculation. The purpose of this study was to directly observe the effects
      of AVP versus PE on inflammatory changes evoked by tumor necrosis factor alpha
      (TNF) in the skeletal muscle microcirculation. METHODS: Seventy-five male rats
      (180-250 g) were anesthetized with isoforane, intubated and mechanically
      ventilated with 100% oxygen. The cremaster muscle microcirculation was prepared
      for intravital video microscopy while being suffused with a heated hetastarch
      electrolyte solution. Fluorescein isothiocyanate-labeled albumin (100 mg/kg) was
      administered intravenously (i.v.) before one of five protocols. In series 1 (n =
      20), either AVP (0.2 U/mL) or its vehicle was added to the suffusate for 10
      minutes, washed out for 30 minutes, then TNF was suffused (5 ng/mL) for 30
      minutes. In series 2 (n = 16), the protocol was similar, except AVP (0.2 U/mL) or
      an equieffective dose of PE (0.04 mg/mL) was administered i.v. (4.5 mL/h) for 15
      minutes before, during, and 45 minutes after TNF suffusion. In series 3 (n = 12),
      the protocol was similar to series 2, except venous hemorrhage preceded i.v. AVP
      or PE. In series 4 (n = 15), the protocol was similar to series 3, except an AVP
      antagonist (vaprisol, 1 mg/kg i.v.) or its vehicle was administered after
      hemorrhage. In the control series (n = 13), inflammation was evaluated either
      with a different suffusate (lactated Ringers instead of hetastarch solution),
      different antigen (histamine instead of TNF), or hemorrhage with no antigen.
      RESULTS: In series 1, the TNF-evoked increase in leukocyte infiltration (i.e.,
      rolling), leukocyte activation (i.e., sticking), and macromolecular permeability
      (i.e., albumin extravasation) were attenuated with topical AVP versus vehicle
      (both p < 0.05), with no effect on venular blood flow (which determines sheer
      stress). In series 2, the TNF-evoked increase in infiltration, activation, and
      permeability were all attenuated, and arteriolar blood flow (which determines
      perfused capillary surface area and hydrostatic pressure) was reduced with i.v.
      AVP versus i.v. PE (all p < 0.05). In series 3, after hemorrhage to mean arterial
      pressure <50 mm Hg for 30 minutes, the TNF-evoked increase in infiltration and
      activation was attenuated, and arteriolar and venular blood flow were both
      reduced with i.v. AVP versus PE (all p < 0.05). In series 4, after hemorrhage,
      the TNF-evoked increase in leukocyte activation was potentiated with the vaprisol
      versus vehicle (p < 0.05) with no effect on arteriolar or venular blood flow. In
      series 5 (controls), suffusion with lactated Ringers' versus hetastarch solution
      more than doubled the TNF-evoked increase in activation (p < 0.05). CONCLUSION:
      (1) AVP can attenuate TNF-evoked leukocyte infiltration, activation or
      permeability changes in the skeletal muscle microcirculation. (2) The mechanism
      is probably receptor mediated and does not entirely depend on sheer stress in
      venules or Starling forces in capillaries. (3) The magnitude of this anti
      inflammatory effect is influenced by several conditions, including volume status,
      the colloid or crystalloid suffusion fluid, and is possibly specific to the
      antigenic stimulus (TNF vs. histamine).

PMID- 19741388
TI  - Long-term follow-up of trauma patients with permanent prophylactic vena cava
      filters.
AB  - BACKGROUND: Although permanent prophylactic Greenfield filters (PPGF) are
      effective, their use in young trauma patients who may eventually return to active
      lifestyles is controversial due to concerns about the safety of the devices over
      a lifetime. This descriptive study was undertaken to provide follow-up on the
      long-term safety and durability of PPGF. METHODS: All patients receiving a PPGF
      between April 1, 1992 and March 1, 2001 were sought for follow-up. Contacted
      patients were interviewed regarding known filter-related complications, venous
      thromboembolic events, and activity levels since the time of discharge from the
      hospital. Patients were also offered a physical examination focusing on venous
      thromboembolic sequelae, a plain film of the abdomen (KUB) to assess filter
      integrity and location, and an ultrasound to assess caval patency. As the
      original level of filter placement was usually not known, migration was defined
      as a filter above the first lumbar vertebra (L1). RESULTS: The eligible cohort
      consisted of 188 patients. Ninety were unable to be located (47.8%), one refused
      enrollment (0.5%), and 97 patients or next of kin agreed to be interviewed by
      phone (51.6%) of whom 69 returned for evaluation (36.7%). No filter-related
      complications were self-reported. KUBs were performed in 68 patients; one filter
      strut fracture was found (1.5%), whereas no filter migrations above L1 were
      noted. No instances of caval thrombosis were found in 55 ultrasounds. Two
      patients suffered interim pulmonary emboli (2.1%), one of which was fatal. Of 15
      interim deaths, autopsy or death certificates were available for four patients,
      nine had their causes of death related by next of kin, and two were unknown.
      Although 95.4% of nonspinal cord injury patients reported at least some ability
      to ambulate, only 64.6% could do so ad libitum. Of those patients ambulating
      without limitation, 28.6% reported a complete inability to run any distance and
      another 23.8% could run less than one block. Follow-up for patients completing
      interviews was 105.3 months +/- 18.0 months, and for patients undergoing imaging
      was 104.6 months +/- 16.4 months. Interim deaths occurred at 48.2 months +/- 26.0
      months. CONCLUSIONS: PPGF seem to be safe and effective at 105 months of follow
      up; most patients report significant limitations in activity level at this same
      timeframe. PPGF should be the filter of choice for elderly patients in whom this
      time period can reasonably be expected to cover the patient's remaining life
      expectancy.

PMID- 19741387
TI  - Preinjury statin use is associated with a higher risk of multiple organ failure
      after injury: a propensity score adjusted analysis.
AB  - BACKGROUND: Recent studies suggest that statin use may improve outcome in
      critically ill patients. This has been attributed to the pleiomorphic effect and
      modulation of inflammatory mediators that occurs with statin use. We sought to
      determine whether preinjury statin (PIS) use was associated with improved outcome
      in severely injured blunt trauma patients. METHODS: Data were obtained from a
      multicenter prospective cohort study evaluating outcomes in blunt injured adults
      with hemorrhagic shock. Patients aged 55 years and older were analyzed. Those
      with isolated traumatic brain injury, cervical cord injury, and those who
      survived <24 hours were excluded. A propensity score predicting statin use was
      created using logistic regression. Cox proportional hazard regression was then
      used to evaluate the effects of PIS use on mortality and the development of
      multiple organ failure (MOF, multiple organ dysfunction syndrome >5) and
      nosocomial infection (NI) after adjusting for important injury characteristics
      and the propensity of taking PISs. RESULTS: Overall mortality and MOF rates for
      the study cohort (n = 295) were 21% and 50%, respectively. Over 24% of patients
      (n = 71) reported PIS use. Kaplan-Meier analysis revealed no difference in NI or
      mortality over time but did show a significant higher incidence of MOF in those
      with PIS use (p = 0.04). Regression analysis verified PIS was independently
      associated with an 80% higher risk of MOF (hazard ratio: 1.8; 95% confidence
      interval, 1.1-2.9) and was found to be one of the strongest independent risk
      factors for the development of MOF. CONCLUSION: PIS use was independently
      associated with a higher risk of MOF postinjury. These results are contrary to
      previous analyses. The protective effect of statins may be lost in the severely
      injured, and modulation of the inflammatory response may result in higher
      morbidity. Further studies are required to better understand the impact and
      potential therapeutic utility of this commonly prescribed medication both before
      and after injury.

PMID- 19741389
TI  - Suicides, homicides, and unintentional injury deaths after trauma center
      discharge: cocaine use as a risk factor.
AB  - BACKGROUND: : To study whether trauma center patients with positive toxicology
      findings for cocaine-positive (COC+) are at a higher risk for suicide, homicide,
      and unintentional injury death after discharge than cocaine-negative (COC+)
      trauma patients. METHODS: : Patients admitted between July 1983 and June 1995 and
      discharged alive from a level I trauma center were prospectively followed up for
      1.5 years to 14.5 years. The occurrence of suicide, homicide, and unintentional
      injury death was explored in relation to COC+ status at admission using Cox
      proportional hazards methodology. Models included possible confounders.
      Interactions with each of the main effects were explored. RESULTS: : Of the
      27,399 admissions, 21,500 had urine COC toxicology testing performed and were
      included in the study. COC was positive in 11.4% of the studied population. COC+
      patients were significantly younger, with 72% of COC+ versus 43% of COC- in the
      25 to 44 years age group. COC+ patients were more likely to be men, positive for
      alcohol, and intentional injury victims. COC+ status was not associated with
      subsequent suicide. Furthermore, the COC+ status association with subsequent
      homicide became nonsignificant after adjusting for confounders. Unadjusted COC+
      status was associated with unintentional injury death (odds ratio = 1.65 [1.14
      2.40]). Interactions were found in the association with unintentional injury
      death such that COC+ status tripled the odds of injury death (odds ratio = 2.75
      [1.58-4.78]) among the alcohol-negative patients within the 25 to 45 years age
      group. CONCLUSION: : COC+ trauma patients are at an increased risk of subsequent
      unintentional injury death after discharge from a trauma center. Suicide and
      homicide occurrence seems to be unaffected.

PMID- 19741390
TI  - Alcohol and high-risk behavior among young first-time offenders.
AB  - BACKGROUND: Underage drinking carries a high risk of injury. An important
      approach for reducing underage drinking is limiting youth access to alcohol.
      Underage drinkers obtain alcohol from multiple sources and patterns of access may
      vary by region. We examined patterns of access to alcohol and alcohol use among
      youth in a local court-ordered diversion program for first-time adolescent
      alcohol offenders as a basis for designing and evaluating community prevention
      efforts. METHODS: Youth in the program completed a survey of demographic data,
      type of offense, source, setting, and quantity of alcohol consumed at time of
      offense, and 1-year alcohol-related high-risk behaviors. Significance was
      attributed to p < or = 0.05. RESULTS: Completed surveys were obtained from 1,158
      (84.8%) of 1,366 eligible participants during the 23-month study period. There
      were 71% males and 29% females with a mean age of 17.2 years (range, 12-24
      years). Respondents were Caucasian (64.5%), Hispanic/Latino (19.9%), Asian
      (3.5%), African American (2.5%), and others (9.6%). Offenses included minor in
      possession (55.8%), driving under the influence (21.2%), and drunk in public
      (20.4%). Consumption at time of offense was one or less drinks in 36.3%, two to
      five drinks in 31.7%, and 32.0% reported six or more drinks. Social sources of
      alcohol (got it from someone else) were reported by 72.9% and commercial sources
      (bought it or took it from a store) were reported in 11.9%. The two most common
      places of consumption were someone else's home (30.7%) and the beach (14.6%).
      Multiple 1-year high-risk behaviors were reported and 41.0% drove after drinking
      or rode with someone else who had been drinking. Binge drinking (5 or more drinks
      for males; 4 or more drinks for females) was reported by 43.1% of males and 36.7%
      of females. All high-risk behaviors were more common in binge drinkers (p <
      0.001). Drinking and driving or riding with a drinking driver was reported in
      54.2% of those who binged. Females who binged reported a higher rate than males
      in 8 of 10 high-risk behaviors. CONCLUSIONS: This study revealed the predominance
      of social sources of alcohol among young first-time alcohol offenders. Drinking
      and driving or riding with a drinking driver was reported at an alarmingly high
      rate. Other alcohol-related high-risk behaviors were also common. Efforts to
      prevent alcohol-related trauma should target social access to alcohol, the
      resulting high-risk behaviors, and include a special focus on young females.

PMID- 19741391
TI  - Firearm suicide among veterans in the general population: findings from the
      national violent death reporting system.
AB  - BACKGROUND: Military veterans are particularly vulnerable to suicide compared
      with their civilian peers. Scant attention has been devoted to the problem of
      firearm suicide among veterans, particularly women. The purpose of this study was
      to examine the rate, prevalence, and relative odds of firearm use among veteran
      suicide decedents in the general population. METHODS: The analyses are based on
      data derived from 28,534 suicide decedents from the 2003 to 2006 National Violent
      Death Reporting System. RESULTS: Across the age groups, male and female veterans
      had higher firearm suicide rates than nonveterans. Among males and females,
      younger veterans (18-34 years) had the highest firearm and total suicide rates.
      The male and female veteran suicide decedents were, respectively, 1.3 and 1.6
      times more likely to use firearms relative to nonveterans after adjusting for
      age, marital status, race, and region of residence. CONCLUSIONS: Although violent
      death and the use of firearms are generally associated with men, the results
      reported here suggest that firearms among female veterans deserve particular
      attention among health professionals within and outside the veterans affairs
      system. In addition, the focus should not be exclusively on the Operation
      Enduring Freedom/Operation Iraqi Freedom military cohort but also on men and
      women who served in earlier combat theaters, including the Gulf war, Vietnam Era,
      Korean Conflict, and World War II.

PMID- 19741392
TI  - Early progression of traumatic cerebral contusions: characterization and risk
      factors.
AB  - BACKGROUND: Traumatic intracerebral contusions carry a high rate of early
      progression and are associated with morbidity and mortality. Our objectives were
      to better characterize the prevalence of progression of traumatic contusions,
      risk factors, and the association with outcome. METHODS: Participants were 46
      patients with traumatic intracerebral contusion who underwent a repeat computed
      tomography (CT) scan within 24 hours of injury. Hemorrhage volume on the CT scan
      was quantified using the ABC/2 technique. Univarite and multivariate statistics
      were used to define growth (percentage increase and absolute volume increase), to
      examine the relationship between the risk factors of interest and hemorrhage
      expansion, and with neurologic function and discharge destination. RESULTS: Sixty
      five percent of the patients experienced progression in the size of the lesion in
      the initial 24 hours postinjury. The international normalized ratio was
      significantly higher in the group that demonstrated progression. Deterioration on
      the Glasgow Coma Score was associated with a threefold risk of hemorrhage
      expansion being found on the CT as defined by percentage increase (odds ratio
      [OR] = 3.43; 95% confidence interval [CI]: 0.90 to 13.10) and similarly when
      defined as absolute increase in volume (OR = 3.32; 95% CI: 0.96 to 11.41).
      Controlling for injury severity, there was an association between hemorrhage
      growth and death with those displaying progression more likely to die during
      hospitalization (OR = 1.08; 95% CI: 0.97 to 1.20). CONCLUSION: A high proportion
      of intracerebral contusions evolve in size very early in the postinjury period
      and are associated with negative outcomes. There is still not a proven therapy
      for limiting the expansion although the association of an elevated international
      normalized ratio with expansion suggests that coagulation abnormalities must be
      actively corrected.

PMID- 19741393
TI  - Concomitant cranial and ocular combat injuries during Operation Iraqi Freedom.
AB  - BACKGROUND: Concomitant cranial and ocular injuries were frequently seen in
      combat casualties during Operation Iraqi Freedom. The incidence of these injuries
      is reported along with an interventional case series. METHODS: A retrospective
      review was conducted of all surgical patients treated by U.S. Army neurosurgeons
      and ophthalmologists in Iraq from December 2005 to April 2006. RESULTS: Out of
      104 patients with cranial trauma and 158 patients with ocular trauma, 34 had both
      cranial and ocular injuries (32.7 and 21.5% of patients with cranial and ocular
      injuries, respectively). Neurosurgical procedures included exploratory
      craniotomy, decompressive craniectomy, and frontal sinus surgery. Ophthalmologic
      surgical procedures included globe exploration, open globe repair, primary
      enucleation, orbital fracture repair, lateral canthotomy and cantholysis, and
      repair of lid and periocular lacerations. Patients with cranial trauma had a
      higher incidence of orbital fracture, orbital compartment syndrome, and multiple
      ocular injuries compared with patients without cranial trauma (odds ratio 6.4,
      3.9, and 3.3, respectively). CONCLUSION: A strong association exists between
      cranial and ocular trauma in combat casualties treated during Operation Iraqi
      Freedom. Combat health support personnel should maintain a high level of
      suspicion for one of these injuries when the other is present. Co-locating
      neurosurgeons and ophthalmologists in support of combat operations facilitates
      the optimal treatment of patients with these combined injuries.

PMID- 19741394
TI  - Secondary intracranial hemorrhage after mild head injury in patients with low
      dose acetylsalicylate acid prophylaxis.
AB  - BACKGROUND: Low-dose acetylsalicylate acid (LDA) therapy is accepted as a major
      risk factor for intracranial hemorrhages (ICH) in head injuries. Coincidentally,
      patient admissions that might be indicated for in hospital observation of
      neurologic function causes increased health care costs. In the literature, there
      is no evidence concerning the incidence of secondary intracranial hemorrhagic
      events (SIHE) in patients with LDA prophylaxis that had negative primary computed
      tomography (CT)-scan of the head. METHODS: In this prospective study, we enrolled
      100 consecutive trauma patients older than 65 years presenting in a Level I urban
      trauma center after a mild head injury (Glasgow Coma Scale score of 15) who had
      LDA prophylaxis. Patients included had a negative primary head CT-scan concerning
      ICH. For analysis of the incidence of SIHEs patients had routine repeat head CT
      (RRHCT) after 12 hours to 24 hours. RESULTS: Sixty-one patients were women and 39
      men. Mean age was 81 years +/- 10 years. Injury mechanism was a level fall in 84
      cases and others in 16. In four patients (4%) an SIHE was detected in the RRHCT
      (p < 0.00001). In two patients (2%) major secondary ICH had occurred without
      neurologic deterioration at the time of RRHCT with fatal outcome in one patient
      and neurosurgical intervention in another. The remaining two patients (2%) had
      minor SIHE with an uneventful clinical course. CONCLUSION: The incidence of SIHE
      has been neglected until now. The current study revealed that patients with LDA
      prophylaxis after mild head injury with negative primary head CT should be
      subjected to RRHCT within 12 hours to 24 hours to accurately identify SIHE.
      Alternatively to RRHCT, patients should be subjected to a prolonged in-hospital
      observation for at least 48 hours.

PMID- 19741395
TI  - Concordance of end-tidal carbon dioxide and arterial carbon dioxide in severe
      traumatic brain injury.
AB  - OBJECTIVE: It is important for preventing hyperventilation so as to improve the
      outcomes of patients with severe traumatic brain injuries. End-tidal CO2 (Petco2)
      reflects arterial CO2 (Paco2), noninvasively and continuously. The aim of this
      study is to examine the concordance between Paco2 and Petco2 among adults
      presenting to the emergency department with severe traumatic brain injury and to
      elucidate the patient groups who had discordance. METHODS: From July 1, 2006 to
      December 31, 2007, 77 patients who presented in the emergency department of the
      hospital after severe brain injury were enrolled. Glasgow Coma Scale, blood
      pressure, heart rate, respiration rate, body temperature, arterial blood gas
      variables, and serum lactate levels were measured under the mechanical
      ventilation support. Finally, Injury Severity Score and Abbreviated Injury Scale
      of head and chest were recorded. The concordance between Petco2 and Paco2 was
      analyzed using Bland-Altman plot. We defined that normal gap of Paco2 and Petco2
      [P(a-et)co2] is -5 mm Hg to 5 mm Hg, and compared the normal and high P(a-et)co2
      groups to find the factors affecting the P(a-et)co2. RESULTS: Sixty-six patients
      after exception of 11 patients with nontraumatic brain injury were analyzed. Ten
      patients (15.2%) were below 30 mm Hg of Paco2. Pearson's correlation coefficient
      between Paco2 and Petco2 was 0.666 (p < 0.001) and the concordance between Paco2
      and Petco2 was 77.3%. The patients with high P(a-et)co2 showed significantly
      higher Injury Severity Score, lower systolic blood pressure, lower arterial pH,
      lower base deficit, and higher serum lactate levels than patients with normal P(a
      et)co2. Patients with severe chest trauma, hypotension, and metabolic acidosis
      increased the risk of the discordance between Paco2 and Petco2. Twenty-eight
      patients who had no hypotension, no metabolic acidosis, and no severe chest
      trauma showed concordance rate of 100.0% between Paco2 and Petco2. CONCLUSIONS:
      Severe chest trauma and hemodynamic and tissue perfusion state should be
      considered when attempting to monitor the hyperventilation in severe brain injury
      patients using Petco2.

PMID- 19741396
TI  - Preemptive craniectomy with craniotomy: what role in the management of severe
      traumatic brain injury?
AB  - BACKGROUND: Patients with severe traumatic brain injury (TBI) require aggressive
      management to prevent secondary brain injury. "Preemptive" craniectomy (CE)-
      craniectomy performed as a primary procedure in conjunction with craniotomy--has
      been used as prophylaxis for secondary injury, but the indications and outcomes
      of craniectomy used for this purpose are not well defined. METHODS: To evaluate
      the role of CE in the management of TBI, we retrospectively reviewed 62
      consecutive patients who underwent CE in a 78-month period at our level I trauma
      center. A cohort of patients who underwent craniotomy only (CO) during this
      period was compared with the CE group for TBI patterns, indications for
      operation, and outcomes. Multivariable logistic regression and matched propensity
      score analysis were used to test the association between CE and survival. The
      rate of CE was determined by individual neurosurgeons. RESULTS: Of 197 patients
      with brain injuries who underwent craniotomy, 62 (31.5%) had CE and 135 (68.5%)
      had CO. Mean age for CE versus CO was 41 years versus 51 years (p < 0.01). Mean
      admission Glasgow Coma Score was lower in CE versus CO (7.6 vs. 11.8, p < 0.001);
      Injury Severity Score was higher (30.2 vs. 26.3, p < 0.01). The indication for
      operation for CE compared with CO was subdural hematoma in 41 (66.1%) versus 87
      (64.4%, p = 0.82), epidural hematoma in 2 (3.2%) versus 26 (19.3%, p < 0.01), and
      cerebral contusion or hematoma in 15 (24.2%) versus 8 (5.9%, p < 0.001).
      Postoperative intracranial pressure was monitored in 48 (77.4%) CE and 44 (32.6%)
      CO patients (p < 0.001). Intracranial pressure <20 was maintained in 26 (54.2%)
      after CE and in 31 (70.5%) after CO (p = 0.12). In the CE group, 26 (42%) died
      compared with 31 (26%, p < 0.01) in the CO group. When adjusted for severity of
      injury, however, there was no significant difference in mortality between the two
      groups (p = 0.134). The CE rate obtained by a neurosurgeon varied from 8.6% to
      75.0% (p < 0.001). CONCLUSION: CE was used in patients with more severe injuries,
      and particularly in those with more severe head injuries. When adjusted for
      injury severity, CE was not associated with worsened survival, and therefore may
      reasonably be included in the armamentarium of neurotrauma care. Use of CE by our
      neurosurgeons, however, varied significantly. These findings underscore the need
      for practice guidelines based on randomized trials to fully evaluate the role of
      CE in the management of TBI.

PMID- 19741397
TI  - Multiple level injuries in pediatric spinal trauma.
AB  - BACKGROUND: The incidence of concomitant, particularly noncontiguous, spine
      injuries in the pediatric population has not been well described. There is a
      balance between limiting radiation exposure and not missing concomitant injuries;
      understanding of this risk of concomitant spine injuries in this population is
      important. We hypothesize that the rate of concomitant spinal injuries in
      children is similar to adults. METHODS: The trauma registry of a pediatric trauma
      center was queried for all patients who sustained spine injuries over a 10-year
      period. Patient demographics, presence of other injuries, treatment, location and
      nature of the spine injury, as well as presence of multiple level injuries were
      determined. RESULTS: One hundred and ninety-five patients with spine injuries
      were noted. Patients over age 8 years accounted for 76% of spine injuries (148 of
      195). Concomitant injuries to other levels in the spine occurred in 32% of the
      patients (62 of 195); 6% of these secondary injuries were noncontiguous and were
      at least three levels away from the primary injury. All of the concomitant
      injuries were either in the thoracic or in the upper lumbar spine. Neurovascular
      status and mechanism of injury were not different between patients sustaining
      concomitant injuries or not. CONCLUSIONS: Pediatric spine injuries are more
      common in patients over age 8 years of age; these patients are more likely to
      have multiple levels of injury. Of patients sustaining a spine injury, 6% had
      noncontiguous second fractures, which is a rate similar to adults. Imaging
      studies evaluating patients with spinal injuries should include at least three
      levels above and below the primary level of injury as well as the entire thoracic
      spine and thoracolumbar junction.

PMID- 19741398
TI  - Clinical clearance of the cervical spine in blunt trauma patients younger than 3
      years: a multi-center study of the american association for the surgery of
      trauma.
AB  - BACKGROUND: Cervical spine clearance in the very young child is challenging.
      Radiographic imaging to diagnose cervical spine injuries (CSI) even in the
      absence of clinical findings is common, raising concerns about radiation exposure
      and imaging-related complications. We examined whether simple clinical criteria
      can be used to safely rule out CSI in patients younger than 3 years. METHODS: The
      trauma registries from 22 level I or II trauma centers were reviewed for the 10
      year period (January 1995 to January 2005). Blunt trauma patients younger than 3
      years were identified. The measured outcome was CSI. Independent predictors of
      CSI were identified by univariate and multivariate analysis. A weighted score was
      calculated by assigning 1, 2, or 3 points to each independent predictor according
      to its magnitude of effect. The score was established on two thirds of the
      population and validated using the remaining one third. RESULTS: Of 12,537
      patients younger than 3 years, CSI was identified in 83 patients (0.66%), eight
      had spinal cord injury. Four independent predictors of CSI were identified:
      Glasgow Coma Score <14, GCSEYE = 1, motor vehicle crash, and age 2 years or
      older. A score of <2 had a negative predictive value of 99.93% in ruling out CSI.
      A total of 8,707 patients (69.5% of all patients) had a score of <2 and were
      eligible for cervical spine clearance without imaging. There were no missed CSI
      in this study. CONCLUSIONS: CSI in patients younger than 3 years is uncommon.
      Four simple clinical predictors can be used in conjunction to the physical
      examination to substantially reduce the use of radiographic imaging in this
      patient population.

PMID- 19741399
TI  - CTA-based screening reduces time to diagnosis and stroke rate in blunt cervical
      vascular injury.
AB  - BACKGROUND: Advances in computed tomography capabilities have enabled trauma
      surgeons to screen for and diagnose the severity of blunt cervical vascular
      injury (BCVI) using computed tomographic angiography (CTA) alone. We hypothesized
      that the use of CTA-alone screening and diagnostic methods would reduce the time
      interval from admission to diagnosis and, hence, also reduce the stroke rates
      associated with these injuries. METHODS: All patients admitted to a level I
      trauma center after December 1999 at risk for BCVI were screened. Until March
      2005, patients were screened with cervical catheter angiography (CA).
      Subsequently, a CTA-alone screening/diagnostic program was initiated
      simultaneously with standardized interdisciplinary treatment guidelines for BCVI.
      Data for controls were subsequently obtained by reviewing trauma registry
      records. RESULTS: Of 3012 trauma service admissions from April 2005 to July 2006,
      26 patients were found to have BCVI diagnosed by CTA alone. A standardized,
      injury grade-based set of treatment guidelines were then initiated immediately
      based on CTA findings. Time to diagnosis and stroke rate in these patients were
      then compared with 79 patients found to have BCVI from December 1999 to March
      2005 during CA-based screening. There were no differences in sex, mean age,
      Injury Severity Score, head/neck Abbreviated Injury Scale, or arrival Glasgow
      Coma Scale between the CA and CTA groups. With CA-based screening, the mean +/-
      SD time from trauma center admission to diagnosis was 31.2 +/- 41.1 hours. After
      transition to CTA screening in March 2005, this time was reduced to 2.65 +/- 3.3
      hours (p < 0.001). During the era of CA-based screening, the overall stroke rate
      for BCVI at our institution was 15.2% (n = 12 of 79). After the initiation of CTA
      based screening, the stroke rate was reduced to 3.8% (n = 1 of 26, p = 0.046).
      CONCLUSIONS: The initiation of a CTA-based screening and diagnostic program,
      along with interdisciplinary standardized treatment guidelines, reduced the time
      to diagnosis of BCVI 12-fold and the institutional stroke rate due to BCVI
      fourfold. This may be due to earlier diagnosis and initiation of definitive
      therapy.

PMID- 19741400
TI  - Does splenic preservation treatment (embolization, splenorrhaphy, and partial
      splenectomy) improve immunologic function and long-term prognosis after splenic
      injury?
AB  - BACKGROUND: : To assess the immunologic alteration and long-term prognosis after
      splenic injury from preservation treatment (PT) (embolization, splenorrhaphy,
      partial splencetomy) and to compare with splenectomy (SN). METHODS: : The long
      term prognosis of patients with blunt splenic injury treated at seven tertiary
      emergency centers in Japan was retrospectively studied. Patients were followed up
      by telephone interview and written questionnaire. Blood samples and abdominal
      computer tomography scans were taken from patients who consented, and immunologic
      indices and the remaining volume of the spleen were measured. RESULTS: : There
      was no episode of severe infection requiring hospitalization among the 66 SN
      patients (760 patient-year) and the 34 PT (213 patient-year) patients. Blood
      tests from 58 patients (24 SN vs. 34 PT) revealed significant differences in
      platelet count, Howell-Jolly body positive rate (SN 87% vs. PT 3%), white blood
      cells, total lymphocyte count, T-cell count, B-cell count, and serum IgG level.
      There was no significant difference in serum levels of IgM or specific IgG
      antibodies against 14 types of Streptococcus pneumoniae capsular polysaccharide,
      C3, C4, high-sensitivity C-reactive protein, and B -cell subset (surface marker
      immunoglobulins: IgA, IgG, and IgM). Most patients had anti-S. pneumoniae
      antibody levels less than that of the reference level for multiple serotypes
      (average 3 in SN and 4 in PT). A computer tomography scan was taken from 33 PT
      patients; the volume of spleen remaining averaged 130 mL (range, 48-287 mL).
      CONCLUSION: : PT did not show discernible advantage over SN in immunologic
      indices including IgM and 14 serotypes of anti-S. pneumoniae antibodies,
      suggesting prophylactic measures and close follow-up are necessary after PT and
      SN.

PMID- 19741401
TI  - The effects of splenic artery embolization on nonoperative management of blunt
      splenic injury: a 16-year experience.
AB  - INTRODUCTION: Nonoperative management (NOM) of blunt splenic injury has become
      the preferred treatment for hemodynamically stable patients. The application of
      splenic artery embolization (SAE) in NOM has been controversial. We hypothesized
      that incorporation of initial use of SAE into a practice protocol for patients at
      high risk for NOM failure (contrast extravasation or pseudoaneurysm on computed
      tomography, grade 3 injury with large hemoperitoneum, grade 4 injuries) would
      improve patient outcomes. METHODS: A retrospective analysis of three continuums
      of practice was performed: group I (January 1991-June 1998), SAE not part of
      routine NOM; group II (July 1998-December 2001), introduction and discretionary
      use of SAE; and group III (January 2002-June 2007), standardized use of initial
      SAE for patients considered at high risk of nonoperative failure. The primary
      outcome measure was the success of NOM. Failure of NOM was defined as the need
      for abdominal operation. Secondary outcomes were mortality, length of stay, and
      splenic salvage. RESULTS: Over 16 years, 815 patients with blunt splenic injury
      were treated at our level 1 trauma center. There were 222 patients in group I,
      195 in group II, and 398 in group III. There was an increase in the use of SAE
      over time with a significant improvement in the utilization of NOM (61% in group
      I; 82% in group II; 88% in group III; p < 0.05). This was associated with an
      increase in successful NOM (77%, group I; 94%, group II; 97%, group III; p <
      0.0001 group I vs. group II and III). Mortality, length of stay, and splenic
      salvage were similar in groups II and III but significantly improved when
      compared with group I. CONCLUSIONS: The increased use of initial SAE in high-risk
      patients expanded the successful use of NOM but was not associated with other
      incremental improvements.

PMID- 19741402
TI  - What's the incidence of delayed splenic bleeding in children after blunt trauma?
      An institutional experience and review of the literature.
AB  - BACKGROUND: The existence and incidence of delayed splenic bleeding (DSB) in
      children are controversial but the implications are significant. We sought to
      determine the incidence of DSB in children and to look for similarities between
      reported cases. METHODS: A retrospective cohort study of all children admitted
      from 1992 to 2006 to our level 1 pediatric trauma center with blunt splenic
      injuries to calculate the incidence of DSB. In addition, a systematic review of
      the literature was performed, looking for similarities between reported cases of
      DSB in children since 1980. RESULTS: Three hundred three children were admitted
      with blunt splenic injuries (mean age, 10 years +/- 4.5 years; boys 212 [70%]).
      Two hundred ninety-three (96%) were successfully managed nonoperatively. All
      cause mortality was 20 of 303 (6.6%). We identified 1 of 303 (0.33%) children
      with DSB. The patient was a boy, aged 15 years. He presented 23 days after
      initial injury with DSB causing death. He had an uncomplicated admission after
      his initial grade IV injury. There have been 14 cases of DSB reported in the
      literature since 1980. Twelve (88%) were boys, with a mean age of 14 years +/- 4
      years (with 11 of 14 (79%) being adolescent). The mean time to DSB was 10 days +/
      7 days. There were no similarities in mechanism, imaging characteristics, or
      presence of pseudoaneurysm between cases. CONCLUSION: DSB is exceedingly rare.
      Our institutional incidence is 1 of 303 (0.33%). The number and quality of
      reported cases is insufficient to draw conclusions on predisposing factors for
      DSB, however, most cases occur in adolescents.

PMID- 19741403
TI  - Radiographic predictors of need for angiographic embolization after traumatic
      renal injury.
AB  - BACKGROUND: Although the American Association of the Surgery for Trauma Organ
      Injury Scale is the gold standard for staging renal trauma, it does not address
      characteristics of perirenal hematomas that may indicate significant hemorrhage.
      Angiographic embolization has become well established as an effective method for
      achieving hemostasis. We evaluated two novel radiographic indicators--perirenal
      hematoma size and intravascular contrast extravasation (ICE)--to test their
      association with subsequent angiographic embolization. METHODS: Among 194
      patients with renal trauma between 1999 and 2004, 52 having a grade 3 (n = 33) or
      grade 4 (n = 19) renal laceration were identified. Computed tomography scans were
      reviewed by a staff radiologist and urologist blinded to outcomes. ICE was
      defined as contrast within the perirenal hematoma during the portal venous phase
      having signal density matching contrast in the renal artery. Hematoma size was
      determined in four ways: hematoma area (HA), hematoma to kidney area ratio (HKR),
      difference between hematoma and kidney area (HKD), and perirenal hematoma rim
      distance (PRD). RESULTS: Of the 52 patients, 8 had ICE and 4 of these (50%)
      required embolization, whereas none of the 42 (0%) patients without ICE needed
      embolization (p = 0.001). Likewise, all four measures of perirenal hematoma size
      assessed were significantly greater in patients receiving embolization [HA (128.3
      vs. 75.4 cm, p = 0.009), HKR (2.75 vs. 1.65, p = 0.008), HKD (76.5 vs. 30.2 cm, p
      = 0.006), and PRD (4.0 vs. 2.5 cm, p = 0.041)]. CONCLUSION: Perirenal hematoma
      size and ICE are readily detectible radiographic features and are associated with
      the need for angiographic embolization.

PMID- 19741404
TI  - Single-contrast computed tomography for the triage of patients with penetrating
      torso trauma.
AB  - BACKGROUND: We have used single-contrast (intravenous contrast only) computed
      tomography (SCCT) for triaging hemodynamically stable patients with penetrating
      torso trauma. We hypothesized that SCCT safely determines the need for operative
      exploration. Furthermore, trauma surgeons without specialized training in body
      imaging can accurately apply this modality. METHODS: We retrospectively reviewed
      the records of patients with penetrating torso injuries at a university-based
      urban trauma center to establish the accuracy of SCCT in determining the need for
      exploratory laparotomy. The scan was considered positive or negative with respect
      to the need for exploratory laparotomy as documented by the attending surgeon,
      who may have considered the read of the on call radiologist if available. In a
      separate study, four trauma surgeons independently reviewed 42 SCCT scans to
      establish whether the scans alone could be used to determine whether operative
      exploration was necessary. RESULTS: Between 1997 and 2008, 306 hemodynamically
      stable patients with penetrating torso trauma were triaged by SCCT. Overall, SCCT
      predicted the need for laparotomy with 98% sensitivity and 90% specificity. The
      positive predictive value was 84% and the negative predictive value (NPV) was
      99%. In the 222 patients with gunshot wounds, SCCT had 100% sensitivity and 100%
      NPV. In the 84 patients with stab wounds, SCCT had 92% sensitivity and 97% NPV.
      Trauma surgeon agreement in the retrospective review of 42 computed tomography
      scans was "nearly perfect": positive predictive value was 93% and NPV was 92% for
      determining the need for exploratory laparotomy surgery. CONCLUSIONS: SCCT is
      safe and effective for triaging hemodynamically stable patients with penetrating
      torso trauma. It successfully determined the need for operative intervention with
      appropriate clinical accuracy without the additional costs, morbidity, and delay
      of oral and rectal contrast. Trauma surgeons can reproducibly interpret SCCT with
      high-predictive accuracy as to whether patients with penetrating torso trauma
      require operative exploration.

PMID- 19741405
TI  - Standard examination system for laparoscopy in penetrating abdominal trauma.
AB  - BACKGROUND: The high missed occult small bowel injuries (SBI) associated with
      laparoscopy in trauma (LIT) is a major reason why some surgeons still preclude
      LIT today. No standardized laparoscopic examination for evaluation of the
      peritoneal cavity is described for trauma. The objective of this article is to
      verify if a systematic standardized laparoscopic approach could correctly
      identify SBI in the peritoneal cavity for penetrating abdominal trauma (PAT).
      METHODS: Victims with PAT were evaluated in a prospective, nonrandomized study. A
      total of 75 hemodynamically stable patients with suspected abdominal injuries
      were operated by LIT and converted to laparotomy if criteria were met: SBI and
      lesions to blind spot zones--retroperitoneal hematoma, injuries to segments VI or
      VII of the liver, or injuries to the posterior area of the spleen. Inclusion
      criteria were equivocal evidence of abdominal injuries or peritoneal penetration;
      systolic blood pressure >90 mm Hg and <3 L of IV fluids in the first hour of
      admission; Glasgow Coma Scale score >12; and age >12 years. Exclusion criteria
      were back injuries; pregnancy; previous laparotomy; and chronic cardiorespiratory
      disease. RESULTS: Sixty patients were males and there were 38 stab wounds and 37
      gunshot wounds. No SBI was missed, but a pancreatic lesion was undiagnosed due to
      a retroperitoneal hematoma. Twenty patients (26.6%) were converted. Unnecessary
      laparotomies were avoided in 73.33%. Therapeutic LIT was possible in 22.7%.
      Accuracy was 98.66% with 97.61% sensitivity and 100% specificity. CONCLUSIONS:
      Standard systematic laparoscopic exploration was 100% effective to detect SBI in
      the peritoneal cavity. Conversion from LIT to laparotomy should be done if
      injuries to blind spot zones are found which are poorly evaluated by LIT.
      Therapeutic LIT is feasible in PAT.

PMID- 19741406
TI  - Surgical stabilization of rib fractures using Inion OTPS wraps--techniques and
      quality of life follow-up.
AB  - BACKGROUND: A variety of operative techniques have been described in the past for
      the surgical stabilization of fractured ribs. METHODS: From February 2004 to
      November 2008, consecutive patients who underwent open reduction and internal
      fixation of traumatic fractured ribs during their index admission using the Inion
      orthopedic trauma plating system (OTPS) at a Level I trauma center were
      retrospectively analyzed. Demographics, Injury Severity Scores, number and site
      of rib fractures, operative details, and complications were recorded. All
      patients were followed-up with a questionnaire assessing chest symptoms,
      disability, and quality of life. RESULTS: Thirty-two patients underwent surgical
      stabilization with Inion OTPS. Road crashes were the commonest mechanism of
      injury (81%), followed by falls. Seventy-two percent of patients were male, with
      a median age at operation of 53 years (interquartile range [IQR], 40-64 years).
      Median number of ribs fixed was 3 (IQR, 2-4), while median number of fractures
      was 9 (IQR, 6-13). Median time to fixation was 5 days (IQR, 3-7 days), intensive
      care unit stay 3 days (IQR, 0.8-6.3 days), and total hospital stay 13.5 days
      (IQR, 8.8-22 days). Wound infection occurred in 19%, with nonunion of a fixed
      fracture in one patient. Sixty-three percent of patients completed the survey
      with a mean time between open reduction and internal fixation and questionnaire
      of 1,039 days (+/-480 days). Patients reported low levels of pain at rest and
      with coughing (median at rest 1.0/10 [IQR, 0-2.3/10]; with coughing 1.3/10 [IQR,
      0-3.75/10]). Chest wall stiffness was experienced by 60% of patients, while
      dyspnoea at rest was reported by 20% of patients. Mean return to work (for 55%)
      was 3.9 months (+/-3.3 months). All patients were satisfied with the results of
      their operation. CONCLUSION: Patients demonstrated low levels of pain and
      satisfactory rehabilitation. The Inion OTPS system has several advantages
      including gradual transference of stress loads to bone, micromotion across the
      fracture site, and easy wrapping of comminuted fractures. This technique allows
      excellent stabilization of fractured ribs, with good clinical results in ambulant
      and ventilated patients, both with initial and with midterm follow-up.

PMID- 19741407
TI  - Safety and efficacy of damage control external fixation versus early definitive
      stabilization for femoral shaft fractures in the multiple-injured patient.
AB  - BACKGROUND: Optimal timing and treatment of patients with concomitant head,
      thoracic, or abdominal injury and femoral shaft fracture remain controversial.
      This study examines acute patient outcomes associated with early total care with
      intramedullary nailing (ETC group) versus damage control external fixation (DCO
      group) for multiple-injured patients with femoral shaft fractures. We propose DCO
      as a safe initial treatment for the multiple-injured patient with femur shaft
      fractures. METHODS: This study was a retrospective review of the trauma registry
      and multisystem organ failure registry data at a Level I trauma center. Two
      cohorts were identified to compare multiple-injured patients with femoral shaft
      fractures treated with early total care and damage control orthopaedic surgery.
      Primary outcome measures included mortality, pulmonary complications (adult
      respiratory distress syndrome [ARDS] score), transfusion requirements, and
      multiple organ failure (MOF score). Operative time, estimated blood loss,
      intensive care unit length of stay (LOS), and hospital length of stay (LOS) were
      also compared. RESULTS: During the study period, 462 patients with 481 femoral
      shaft fractures were identified. Of 462 patients with femoral shaft fractures, 97
      met the inclusion criteria (42 ETC and 55 DCO). The DCO group had a significantly
      shorter operative time (22 minutes vs. 125 minutes) and less estimated blood loss
      from their operative procedure (37 mL vs. 330 mL). There was no significant
      difference between the groups for ARDS, lung scores, MOF, MOF score, intensive
      care unit LOS, or hospital LOS. CONCLUSION: Fracture fixation method did not have
      an impact on the incidence of systemic complications in multiple-injured patients
      with femoral shaft fractures. Although minimal differences were noted between DCO
      and ETC groups regarding systemic complications, DCO is a safer initial approach,
      significantly decreasing the initial operative exposure and blood loss.

PMID- 19741408
TI  - Proximal humerus intraosseous infusion: a preferred emergency venous access.
AB  - PURPOSE: To assess the proximal humerus intraosseous (PHIO) catheter placement as
      a preferred method for venous access over conventional methods, including
      peripheral intravenous (PIV) and central venous catheters (CVCs), during
      emergency room resuscitation. METHODS: In phase 1, conventional methods for
      venous access (PIV and CVC) were assessed for all patients presenting to the
      emergency department resuscitation bay. Outcome measures in both phases were
      speed, immediate complications, and pain. CVC placement was performed when PIV
      access was deemed impossible or when rapid volume resuscitation was needed. In
      phase 2, resuscitations requiring venous access or complicated by failed PIV
      access attempts underwent PHIO catheter placement. RESULTS: Sixty-two patients
      received either PIV (57) or CVC (5) catheterization, and 29 patients received 30
      PHIO catheters. PHIO catheter placement was significantly faster than
      conventional methods (1.5 [SD 1.1] versus 3.6 minutes [SD 3.7; p < 0.001 for PIV,
      and 15.6 minutes [SD 6.7; p < 0.0056] for CVC). No major complications were
      identified in either phase. Minor complications for PIV access included
      extravasation and placement failure. Minor complications for CVC placement
      included inability to thread the guidewire. Minor complications with PHIO
      catheter placement included placement failure, poor flow, and catheter
      dislodgement. Pain scores associated with PHIO insertion and infusion were higher
      than those associated with PIV and CVC catheter placement. CONCLUSION: PHIO
      catheter placement is significantly faster than PIV and CVC placement with
      increased minor complication profile and perceived pain. PHIO venous access is
      absolutely life saving when PIV or CVC placement is difficult or impossible.

PMID- 19741409
TI  - Displaced distal radial fractures treated using volar locking plates: maintenance
      of normal anatomy.
AB  - BACKGROUND: The objective is to assess the ability of volar locking plates to
      maintain fracture reduction when used to treat dorsally displaced extra- and
      intra-articular distal radial fractures. METHODS: This prospective study was
      conducted over an 12-month period. Consenting patients who had sustained a
      closed, dorsally displaced distal radial fracture, treated by open reduction and
      internal fixation using a volar distal radial locking plate were included in the
      study. Radial inclination, volar tilt, and ulnar variance were measured from
      radiographs taken at least 3 months after surgery and compared with radiographs
      of the uninjured side. Only two of the eight participating surgeons have a
      specialist interest in upper limb surgery. RESULTS: Thirty-three patients were
      included in the study. There were 23 women and 10 men. The mean age was 49.5
      years (range, 26-82 years). According to the Orthopaedic Trauma Association (OTA)
      classification, there were 19 Type A, 1 Type B, and 13 Type C fractures. The
      average restoration of volar tilt was 1-degree angle of under correction with a
      range of 7.3-degree angle of under correction to 3.7-degree angle of over
      correction, when compared with the uninjured side. The mean restoration of radial
      inclination was 1.9-degree angle of under correction with a range of 10-degree
      angle of under correction to 8.4-degree angle of over correction. As a group, the
      mean ulnar variance was 0 mm with a range of 2 mm of relative ulnar shortening to
      3.5 mm of ulnar prominence when compared with the uninjured side. CONCLUSION: In
      the hands of general trauma surgeons, the volar approach combined with the
      application of a suitable volar locking plate is a good treatment for restoring
      and maintaining the anatomy of dorsally displaced intra- and extra-articular
      distal radial fractures.

PMID- 19741410
TI  - Humane killers, human injury: functional outcome of vole captive bolt injuries.
AB  - BACKGROUND: High-pressure blast injuries to the hand due to vole captive bolt
      devices are serious injuries that are to a great extent unknown to emergency care
      operators and trauma surgeons. There is no study on the functional outcome of
      these patients. METHODS: We assessed the functional outcome of patients with
      injuries inflicted by vole captive bolt devices. Therefore, a protocol consisting
      of a physical examination and an assessment of static muscle power (grip and
      pinch strength) was performed. To capture the subjective experience of patients
      regarding their injury related disability and impairment, the DASH follow-up
      questionnaire was used. Based on clinical/radiologic findings and outcome, a
      classification of this unique subgroup of blast injuries was developed. RESULTS:
      The functional outcome of 34 patients suffering hand injuries due to captive bolt
      devices between 2004 and 2007 was assessed. A significant reduction of static
      muscle testing parameters compared with the uninjured hand was revealed. Fourteen
      patients lost a digit. Average time lost from work was 5.4 weeks. CONCLUSION:
      Vole captive bolt device-related hand injuries are followed by deterioration of
      hand function. The present observations alarmed national authorities. The
      manufacturers were required to take engineering and teaching measures to rule out
      handling errors that were identified as leading cause of injury.

PMID- 19741411
TI  - Potential dysregulation of the pyruvate dehydrogenase complex by bacterial toxins
      and insulin.
AB  - BACKGROUND: The pyruvate dehydrogenase complex (PDC) catalyzes the conversion of
      pyruvate to acetyl CoA, effectively controlling the entrance of glycolysis
      products into aerobic metabolism. Because hyperlactatemia is one of the hallmarks
      of sepsis, we hyphothesized that gram-positive and negative bacterial toxin
      treatment will interfere with mRNA levels of regulatory enzymes of the PDC and
      overall enzyme activity in hepatocytes. METHODS: HEP G2 hepatocarcinoma cells
      were incubated for 24 hours in the presence of lipopolysaccaride (LPS) or
      lipoteichoic acid. Total RNA was then isolated and message RNA levels for both
      pyruvate dehydrogense kinase 4 and phosphatase 2 were determined by RTPCR.
      Amplified DNA fragments were visualized by ethidium bromide in agarose gels and
      densitometry of the bands was performed. Data were then normalized to the
      housekeeping gene, GAPDH. Enzyme activity was then determined by capturing intact
      PDC on nitrocellulose membranes then determining PDC-dependent production of
      NADH. RESULTS: LPS treatment led to a time dependent increase in PDK4 message
      while decreasing PDP2 levels. Enzyme activity, in these cells, also significantly
      decreased 24 hours after exposure to LPS. Cells cultured in the presence of
      lipoteichoic acid and insulin exhibited differing message ratios and activity
      levels when evaluated at 4 hours, but at 24 hours shifted to mimic those observed
      in LPS treated cells. CONCLUSION: This data may indicate that exposure to
      bacterial cell wall components and insulin could create cellular environments
      that result in a build-up of lactate.

PMID- 19741412
TI  - Electronic medical records and mortality in trauma patients.
AB  - BACKGROUND: The Electronic Medical Record (EMR) has been proposed as a way to
      reduce medical errors. It can also be used to document clinician involvement,
      which may affect outcomes. We sought to determine whether the EMR could be used
      to improve attending involvement in daily care, enhance surgical revenue, and
      lower mortality of patients with trauma. METHODS: In 2004, the Trauma Division
      adopted a software program (CARE, Miami, FL) for creating an EMR and implemented
      a weekly report that was distributed to all members of the division and also to
      Departmental decision makers. Before initiation, explicit instructions were given
      to all surgeons that daily notes in the EMR were expected and would be followed
      by weekly reports. Before this, most notes were recorded in the paper chart and
      were difficult to track. Differences among proportions were determined with z
      test or chi, where appropriate with significance defined as p < 0.05. RESULTS:
      With implementation of the EMR, daily and weekly reports were immediately
      available. Both attending surgeon documented notes and divisional annual revenue
      increased. A reduction in mortality was also observed. CONCLUSION: The EMR can be
      used to change attending surgeon involvement in patient care and procedures. The
      increase in attending involvement was associated with an increase in revenue. Use
      of the EMR was associated with a significant reduction in hospital mortality.

PMID- 19741413
TI  - Creating a nationally representative sample of patients from trauma centers.
AB  - BACKGROUND: The National Trauma Data Bank (NTDB) was developed as a convenience
      sample of registry data from contributing trauma centers (TCs), thus, inferences
      about trauma patients may not be valid at the national level. The NTDB National
      Sample was created to obtain nationally representative estimates of trauma
      patients treated in the US level I and II TCs. METHODS: Level I and II TCs in the
      Trauma Information Exchange Program were identified and a random stratified
      sample of 100 TCs was selected. The probability-proportional-to-size method was
      used to select TCs and sample weights were calculated. National Sample Program
      estimates from 2003 to 2006 were compared with raw NTDB data, and to a subset of
      TCs in the Healthcare Cost and Utilization Project Nationwide Inpatient Sample, a
      population-based dataset drawn from community hospitals. RESULTS: Weighted
      estimates from the NTDB National Sample range from 484,000 (2004) to 608,000
      (2006) trauma incidents. Crude NTDB data over-represented the proportion of
      younger patients (0 years-14 years) compared with the NTDB National Sample, which
      does not include children's hospitals. Few TCs in Trauma Information Exchange
      Program are included in Healthcare Cost and Utilization Project Nationwide
      Inpatient Sample, but estimates based on this subset indicate a higher percentage
      of older patients (age 65 year or older, 23.98% versus 17.85%), lower percentage
      male patients, and a lower percentage of motor vehicle accidents compared with
      NTDB National Sample. CONCLUSION: Although nationally representative data
      regarding trauma patients are available in other population-based samples, they
      do not represent TCs patients and lack the specificity of National Sample Program
      data, which contains detailed information on injury mechanisms, diagnoses, and
      hospital treatment.

PMID- 19741414
TI  - The impact of a new trauma center on an existing nearby trauma center.
AB  - BACKGROUND: New York State's Trauma System has been in place since 1990. At it's
      inception, 36 trauma centers were designated by the state. As of 2002 there were
      50, with more centers applying for designation. The state designation process
      looks at various criteria that include volume and manpower standards. There is no
      review of the impact of a new center on neighboring centers. This impact can
      include issues of residency training, research, and the maintenance of provider
      skills. If provider skills deteriorate, there is a risk for increased mortality.
      This study examines how a new trauma center, in the Bronx, impacted a near-by
      trauma center. METHODS: Data were collected from the trauma and operating room
      registries during the 12-month period before and after the designation of a near
      by trauma center. Data included number of trauma admissions, Injury Severity
      Score (ISS), mechanism of injury, mortality, number of laparotomies and
      thoracotomies, and the type of ambulance used for transport (private vs.
      municipal). RESULTS: There was a 30% reduction in "major" trauma admissions (ISS
      >8) and a 14% reduction in admissions with an ISS >15. This reduction included a
      22% to 29% reduction in the numbers of severe head injury patients, laparotomies,
      and thoracotomies. Mortality rates for patients with ISS 16 to 24 and >24
      increased after the designation. CONCLUSION: The addition of a new trauma center
      in the Bronx had a negative impact on a near-by trauma center. Significant
      reductions in the volume of severely injured patients had a negative impact on
      factors not routinely measured like resident education, staff competency, and
      research. It is possible that these factors are at least partially responsible
      for the increased mortality rates seen after designation. These considerations
      are not routinely considered during the designation of new trauma centers and may
      actually adversely affect the very population it is trying to serve. As trauma
      systems mature, consideration of the impact the new center will have on the
      existing centers must be included in the designation process.

PMID- 19741415
TI  - Practice management guidelines for identification of cervical spine injuries
      following trauma: update from the eastern association for the surgery of trauma
      practice management guidelines committee.
AB  - BACKGROUND: Injury to the cervical spine (CS) is common after major trauma. The
      Eastern Association for the Surgery of Trauma first published its Practice
      Management Guidelines for the evaluation of CS injury in 1998. A subsequent
      revision was published in 2000. Since that time a large volume of literature has
      been published. As a result, the Practice Management Guidelines Committee set out
      to develop updated guidelines for the identification of CS injury. METHODS: A
      search of the National Library of Medicine and the National Institutes of Health
      MEDLINE database was performed using PubMed (www.pubmed.gov). The search
      retrieved English language articles regarding the identification of CS injury
      from 1998 to 2007. The questions posed were: who needs CS imaging; what imaging
      should be obtained; when should computed tomography, magnetic resonance imaging,
      or flexion/extension radiographs be used; and how is significant ligamentous
      injury excluded in the comatose patient? RESULTS: Seventy-eight articles were
      identified. From this group, 52 articles were selected to construct the
      guidelines. CONCLUSION: There have been significant changes in practice since the
      previous CS injury guidelines. Most significantly, computed tomography has
      supplanted plain radiography as the primary screening modality in those who
      require imaging. Clinical clearance remains the standard in awake, alert patients
      with trauma without neurologic deficit or distracting injury who have no neck
      pain or tenderness with full range of motion. Cervical collars should be removed
      as soon as feasible. Controversy persists regarding CS clearance in the obtunded
      patient without gross neurologic deficit.

PMID- 19741416
TI  - Endovascular grafts for treatment of traumatic injury to the aortic arch and
      great vessels.
AB  - BACKGROUND: Treatment of traumatic vascular injury using endovascular techniques
      has evolved as endovascular capabilities have advanced over the past several
      decades. Several endovascular techniques have been employed to address the
      challenges of traumatic arterial injury, including coil embolization and the use
      of stents, which may be either bare metal or covered with graft material.
      Compared with traditional surgical repair, endovascular stent grafting for the
      repair of traumatic arterial injury offers the advantage of decreased morbidity
      because a remote access site may be used, avoiding surgical dissection and
      lengthy operating times. METHODS: A Medline (1995-2007) search was performed to
      find all studies discussing the use of endovascular means to treat
      supradiaphragmatic arterial trauma. RESULTS: In this review of 195 studies
      published between January 1995 and December 2007, the overall technical success
      rate of endovascular treatment of supradiaphragmatic arterial injury was 96.7%,
      and the complication rate was 6.4%. CONCLUSION: The results of this review
      suggest a potential morbidity and mortality benefit over traditional open repair;
      however, long-term data are lacking. Long-term follow-up for stent durability is
      of particular concern in the trauma population, which tends to comprise younger
      patients with minimal atherosclerotic disease. The success of endovascular
      techniques is also limited by the availability of skilled interventionalists,
      properly outfitted angiography suites, and suitable stent graft devices. Despite
      these challenges, the potential advantages of endovascular stenting make it a
      welcome addition to the armamentarium of the vascular interventionalist who
      treats arterial traumatic injuries.

PMID- 19741417
TI  - The "pseudo-lung point" sign: all focal respiratory coupled alternating pleural
      patterns are not diagnostic of a pneumothorax.

PMID- 19741418
TI  - Sonographic depiction of intraperitoneal free air.

PMID- 19741419
TI  - Traumatic adrenal gland hematoma: FAST is an effective tool to screen.

PMID- 19741420
TI  - Models for hemostatic agent testing: control versus fidelity.

PMID- 19741422
TI  - Renal gunshot wound: clinical management and outcome.

PMID- 19741424
TI  - A germline mutation of p14/ARF in a melanoma kindred.

PMID- 19741425
TI  - Dacarbazine induced acute myeloid leukemia in melanoma.

PMID- 19741426
TI  - Human beta-defensins (HBD1 and HBD3) and malignant melanoma susceptibility.

PMID- 19741427
TI  - Learning more about the Japanese hot flash.

PMID- 19741428
TI  - Calcium intake is inversely associated with metabolic syndrome in postmenopausal
      women: Korea National Health and Nutrition Survey, 2001 and 2005.
AB  - OBJECTIVE: Calcium intake is known to be associated with the risk of having
      metabolic syndrome. However, the previous studies did not take into account the
      fact that intestinal absorption and urinary excretion of calcium are estrogen
      dependent, and intestinal absorption efficiency and renal conservation of calcium
      deteriorate after menopause. Therefore, we performed a menopause status-specific
      analysis of the association between calcium intake and metabolic syndrome.
      METHODS: A total of 9,341 participants (4,118 men, 3,359 premenopausal women, and
      1,864 postmenopausal women) from the Korean National Health and Nutrition
      Examination Survey 2001 and 2005 were included in the study. RESULTS: Calcium and
      energy intake were significantly higher in men than in women and were lowest in
      postmenopausal women. On multivariate logistic regression analysis,
      postmenopausal women with calcium intake in the fourth quartile had a lower risk
      of having metabolic syndrome (odds ratio, 0.637; 95% CI, 0.452-0.898) compared
      with women with intake in the first quartile after adjustment for age, body mass
      index, marital status, education level, alcohol intake, smoking history,
      exercise, hormone therapy use, and energy intake. However, no association was
      detected in men and premenopausal women. CONCLUSIONS: Calcium intake is inversely
      associated with the risk of having metabolic syndrome in postmenopausal women.
      Prospective or longitudinal studies concerning sex and menopause status are
      necessary to evaluate an association between calcium intake and metabolic
      syndrome.

PMID- 19741430
TI  - Prompt responses to the administration of ethanol in the treatment of the alcohol
      withdrawal syndrome (AWS).
AB  - OBJECTIVE: To report the beneficial effect of the administration of ethanol in
      the treatment of the alcohol withdrawal syndrome (AWS). METHODS: In 3 instances
      of the AWS in subjects who used alcohol in socially acceptable amounts, ethanol
      was administered in one case intravenously, and in 2 cases orally. RESULTS:
      Symptoms were dramatically relieved in 20, 10 and 5 minutes, respectively.
      INTERPRETATION: 1. This study suggests the greater use of ethanol in the
      treatment of AWS. 2. Withdrawal symptoms occurred in subjects who drank only 30
      to 60 mL of whiskey daily. 3. Withdrawal manifestations may take up to 10 weeks
      to clear. 4. The violent reaction of patients to being restrained physically in
      their management, the restraint reaction, may find its analogy in Watson's
      intolerable restraint reaction in infants.

PMID- 19741431
TI  - Structural chromosomal variations in neurological diseases.
AB  - BACKGROUND: Significant advancement in the identification of genetic mutations
      and molecular pathways underlying Mendelian neurologic disorders was accomplished
      by using the methods of linkage, gene cloning, sequencing, mutation, and
      functional analyses, in the 1990s. Subsequently, the Human Genome Project defined
      the entire sequence of the genome providing reference for any pathologic
      condition, and identified single nucleotide polymorphisms as a means for whole
      genome association studies and linkage disequilibrium mapping in common, complex
      trait diseases. Simultaneously, data also emerged describing the structural
      chromosomal variations, and it became increasingly recognized that in addition to
      the more traditional mutation types, gene copy number variations (CNVs)
      contribute to normal variability in human phenotypes and may underlie the
      development of diseases with Mendelian inheritance, complex trait, or sporadic
      presentation. REVIEW SUMMARY: Here we describe the occurrence of CNVs in the
      human genome, and discuss their importance in health and disease. Targeting the
      practicing neurologist, we review the presently known CNVs with pathogenic
      significance in common neurologic disorders, and highlight new research
      directions in complex trait diseases. CONCLUSIONS: The role of chromosomal
      structural variations in the pathogenesis of neurologic disorders is increasingly
      recognized. Available data may only capture a small subgroup of conditions
      related to these recently discovered genetic variations. The ongoing genome
      studies are expected to reveal structural chromosomal alterations as an
      underlying cause of many as yet poorly understood common diseases. New challenges
      include defining chromosomal break points, evaluating biologic consequences of
      gene dosage effect, and using molecular genetics for personalized therapeutic
      intervention. This survey of the CNV literature was closed in September 2008.

PMID- 19741432
TI  - Neurologic complications in non-neurological intensive care units.
AB  - BACKGROUND: Neurologists are frequently called to evaluate patients in the
      intensive care units who are not waking up. This often poses a diagnostic and
      prognostic dilemma. REVIEW SUMMARY: The initial evaluation starts with
      abstracting the prehospital and in-hospital history, followed by bedside clinical
      and neurologic examination to establish a differential diagnosis. The subsequent
      work-up is based on clinical suspicion where reversible life-threatening causes
      should be immediately identified. After confirming the diagnosis and
      implementation of the appropriate medical management, a prompt family meeting and
      counseling is recommended. The role of neurologists in clinical diagnosis and
      prognostication of the coma patient, as well as diagnosing brain death is
      instrumental. CONCLUSIONS: In this review, we explore a practical systematic
      approach to patients with decreased level of consciousness. The most common
      causes of impaired alertness in different non-neurologic critical care units and
      commonly used prognostication tools are presented. Finally a brief introduction
      of hypothermia, a novel therapeutic approach is also discussed.

PMID- 19741433
TI  - Cardiac effects of carbamazepine treatment in childhood epilepsy.
AB  - OBJECTIVE: Hypotension, bradycardia, and atrioventricular block are well-known
      cardiovascular effects of carbamazepine (CBZ). However, direct effects of CBZ on
      ventricular functions have been rarely encountered. We investigated the effect of
      CBZ on ventricular functions in pediatric patients without previous cardiac
      disease to determine whether CBZ causes ventricular dysfunction or
      electrocardiographic changes in therapeutic doses in children. METHODS: The study
      includes 40 patients (31 boys, 9 girls) with epilepsy who had been treated with
      carbamazepine. Electroencephalography, electrocardiography, echocardiography, and
      cranial imaging were performed on all patients before treatment and were repeated
      at the end of the third and 12th months of treatment. The systolic and diastolic
      thickness of the interventricular septum and the posterior wall of the left
      ventricle and the systolic and diastolic diameter of the left ventricle were
      measured during M-mode investigation. The end-systolic and end-diastolic volumes
      (mL), the stroke volume (mL), fractional shortening (FS), (%) and ejection
      fraction (EF) (%) measurements were obtained from the computer on the
      echocardiography device. RESULTS: In 1-year follow-up, no electrocardiographic
      abnormalities were detected. The FS and EF values showing left ventricular
      function did not show a significant difference (P > 0.05). CONCLUSIONS: CBZ seems
      to be a safe drug in pediatric epileptic patients without any preexisting cardiac
      disease. We suggest that the risk factors should be defined and followed-up
      regarding cardiac function when treatment is initiated in groups with risk
      factors.

PMID- 19741434
TI  - Does multiple system atrophy itself affect sleep structure?
AB  - OBJECTIVES: Reports on sleep in multiple system atrophy (MSA) are rare and many
      confounding variables affect the results. Among them, obstructive sleep apnea and
      periodic limb movements during sleep are very common. We conducted this study to
      see the changes of sleep parameters originating from MSA itself without
      confounders. METHODS: We compared polysomnographic variables of 15 MSA patients
      and 15 age-, gender-, apnea-hypopnea index-, and periodic limb movements index
      matched controls. We also applied cyclic alternating pattern scoring in 7 MSA
      patients and 7 controls. RESULTS: Total sleep time and sleep efficiency are
      decreased in MSA. Wake after sleep onset, sleep onset latency, and stage 2
      latency are prolonged. There is no difference in the proportion of slow wave
      sleep and rapid eye movement sleep between MSA patients and the controls. Cyclic
      alternating pattern scoring shows no difference, either. CONCLUSIONS: MSA itself
      does not affect the macro- and microstructures of sleep. However, patients with
      MSA sleep less and it cannot be explained by obstructive sleep apnea and periodic
      limb movements during sleep.

PMID- 19741435
TI  - Ending the doctor-patient relationship in neurology practice.
AB  - OBJECTIVE: Ending the doctor-patient relationship with "difficult" patients for
      unacceptable behavior is a rare, although documented occurrence, in primary care
      settings. In neurology practice, brain disease or psychiatric comorbidities
      frequently lead to behavioral disorders. Our aim was to determine whether asking
      "difficult" patients to leave medical practice is a common experience among
      neurologists and to identify specific behaviors associated with these events.
      METHODS: A survey was administered to 24 faculty members of the Department of
      Neurology at the Albert Einstein College of medicine. The survey used open- and
      closed-ended questions to elicit and quantify Neurologists' past experience with
      ending the doctor-patient relationship when treating difficult patients. RESULTS:
      Sixty-two percent of the subjects had ever asked a patient to leave their
      practice. Examining by specialty, 50% of the adult and 87.5% of the pediatric
      neurologists had ever had such an event. (P = 0.07). Mean number of events was
      significantly different for adult neurologists (0.81 +/- 1.1) than pediatric
      neurologists (2.5 +/- 1.8) (P = 0.01). The subjects specifically described 32
      circumstances. Most events were caused by disruptive behavior, threats, or an
      inability of the physician and patient (or family) to agree on a plan of care.
      CONCLUSIONS: Most neurologists surveyed had ended the doctor-patient relationship
      with at least 1 difficult patient during the course of their careers; however,
      the frequency of such events seems to be very low. The practice was more common
      among child than adult neurologists. The most frequent causes were disruptive
      behavior in the office, threatening behavior, or complete failure to agree on a
      plan of care. Potential strategies for dealing with the difficult neurologic
      patient are presented.

PMID- 19741436
TI  - Acute disseminated encephalomyelitis-like manifestations in a patient with neuro
      Behcet disease.
AB  - OBJECTIVE: To describe a patient with a rare presentation of neuro-Behcet
      disease. METHODS AND RESULTS: A 42-year-old patient with definite Behcet disease
      was referred to Nemazee Hospital, affiliated to Shiraz University of Medical
      Sciences, Shiraz, South of Iran, with headache, biparesis, left central facial
      palsy, and urinary dysfunction. Brain magnetic resonance imaging revealed a
      hypo/hypersignal lesion in T1-/T2-weighted images in the right cerebral peduncle
      extending to the right basal ganglia. Cervical magnetic resonance imaging showed
      a lesion in the parenchyma of the spinal cord extending from C2 to T1 which was
      iso-hyperintense in T1-/T2-weighted images. Initial cerebrospinal fluid analysis
      revealed significant pleocytosis, hypoglycorrhachia and increased protein
      content. The patient had an incomplete response to treatment with corticosteroids
      and cyclophosphamide. CONCLUSIONS: An acute disseminated encephalomyelitis (ADEM)
      like presentation is a rare manifestation of neuro-Behcet disease.

PMID- 19741437
TI  - Adult onset chronic unihemispheric vasculitis resembling Rasmussen encephalitis.
AB  - INTRODUCTION: Rasmussen encephalitis (RE), a chronic inflammatory unilateral
      brain disease, is usually associated with intractable seizures and progressive
      neurologic deterioration. Despite being initially observed in children, an adult
      form has been more recently recognized. MRI discloses progressive atrophy and
      signal changes through the affected hemisphere, but rarely gadolinium
      enhancement, which when observed requires a brain biopsy to distinguish Rasmussen
      encephalitis from an alternative diagnosis as unihemispheric vasculitis. CASE
      REPORT: An adult patient had at the age of 35 his first generalized seizure
      followed by transient right hemiparesis and aphasia. Two years later, seizures
      relapsed with a gradually increasing frequency associated with progressive
      neurologic deterioration. Repeated brain imaging, revealed progressive atrophy
      and signal changes within the left hemisphere with gadolinium enhancement.
      Histopathology disclosed focal gliosis mainly in white matter and some small
      intraparenchymal arteries, and arterioles with perivascular and intramural
      chronic inflammatory cell infiltrate. CONCLUSION: Unihemispheric chronic
      vasculitis may resemble adult-onset Rasmussen encephalitis, and persistent
      gadolinium enhancement seen on MRI lesions is helpful for the differential
      diagnosis between the 2 conditions.

PMID- 19741438
TI  - Disappearance of episodic weakness during pregnancy in hyperkalemic periodic
      paralysis from the SCNA4 mutation T704M.
AB  - OBJECTIVE: Disappearance of episodic weakness during pregnancy and an increase in
      myotonia after delivery have not been reported in hyperkalemic periodic paralysis
      (hyperPP). CASE REPORT: In a 36-year-old white woman, with typical manifestations
      of episodic weakness of the limb muscles since age 3 years, hyperPP was diagnosed
      by demonstration of the T407M SCNA4 gene point mutation. At age 34 years, the
      index patient became pregnant for the first time. During the first trimester of
      her pregnancy, she noted a marked decrease in the frequency of the hyperPP
      attacks. During the second and third trimesters, the attacks of weakness
      completely disappeared and after delivery the attacks restarted with the same
      intensity and frequency as before pregnancy, but myotonia persisted between the
      attacks. Disappearance of the attacks during pregnancy was attributed to the
      hormonal changes. CONCLUSIONS: Episodic attacks of weakness in hyperPP may
      disappear during the second and third trimesters of pregnancy, and myotonia
      between the attacks may persist after delivery.

PMID- 19741439
TI  - Spinal cavernoma: an unusual cause of acute monoparesis.
AB  - INTRODUCTION: Cavernous hemangiomas or cavernomas are uncommon vascular
      malformations of the central nervous system involving most commonly the cerebral
      hemispheres where they are detected in young to middle aged adults. We present an
      unusual case of acute monoparesis caused by an intramedullary cavernoma in a
      woman of advanced age. CASE REPORT: A 67-year-old woman presented with walking
      difficulties with acute onset 2 months previously. On neurologic examination,
      there was a pure right leg monoparesis with moderate spasticity. Tendon reflexes
      were brisk and there was a Babinski's sign in her right lower limb. The initial
      diagnosis was lacunar stroke, but the brain magnetic resonance imaging revealed a
      right temporal cavernoma-obviously not associated with her monoparesis. The
      consequent spinal MRI revealed an intramedullary lesion at the T1 level,
      consistent with a cavernoma. CONCLUSION: Our patient presented with an acute
      monoparesis because of a spinal cavernoma, a most unusual occurrence.

PMID- 19741440
TI  - Concommitant appearance of glioblastoma multiforme and neurocysticercosis in a
      nonendemic country: a case report.
AB  - Neurocysticercosis (NC) is the most frequent and widespread human
      neuroparasitosis. Glioblastoma multiforme, a not infrequent brain neoplasm in
      young adults, may have a similar clinical and radiologic presentation as NC.
      Coexistence of NC and brain tumors has been very rarely reported and puts into
      question a causal relationship between the 2 diseases. Here we report the case of
      a patient in which glioblastoma multiforme and cysticercosis appeared
      concomitantly, making their clinical distinction very difficult.

PMID- 19741441
TI  - Prolonged dependence of ischemic penumbra on induced hypertension.
AB  - BACKGROUND: Pharmacological elevation of blood pressure in acute stroke due to
      large artery occlusion may enhance collateral blood flow and salvage penumbral
      tissue. The duration of viability of human penumbral tissue under such
      circumstances is unclear. OBJECTIVE: To describe a patient presenting with acute
      middle cerebral artery occlusion treated with induced hypertension who had
      prolonged survival of penumbral tissue with subsequent infarct extension after
      pressor agents were withdrawn. CONCLUSIONS: Enhanced collateral flow by elevation
      of blood pressure may result in prolonged survival of the ischemic penumbra which
      remains dependent on persistent use of pressor agents.

PMID- 19741442
TI  - The role of corticosteroids in the management of chronic subdural hematomas: a
      critically appraised topic.
AB  - BACKGROUND: Chronic subdural hematomas (CSDH) occur most commonly in the elderly
      population. When CSDH patients present with a moderate or severe neurologic
      deficit and are good surgical candidates, surgery is regarded as the ideal
      option. However, CSDH patients often have only mild neurologic deficits or are
      not optimal candidates for surgery. Corticosteroids are often used on these
      subgroups, but the benefit of this intervention is unknown. Optimal treatment for
      these patients is not well established. OBJECTIVE: Critically evaluate the role
      of corticosteroids in the management of CSDH. METHODS: The objective was
      addressed through the development of a structured critically appraised topic.
      This included a clinical scenario with a structured question, search strategy,
      critical appraisal, results, evidence summary, commentary, and bottom line
      conclusions. Participants included consultant and resident neurologists, a
      medical librarian, clinical epidemiologists, and clinical content experts in the
      fields of vascular neurology and neurosurgery. RESULTS: No randomized controlled
      trials on the topic were discovered. A prospective cohort study was selected as
      the best currently available evidence. CONCLUSION: The role of corticosteroids in
      the management of CSDH is not well defined. Current evidence neither supports nor
      refutes the use of corticosteroids. A randomized controlled trial is warranted.

PMID- 19741443
TI  - Patient and family fact sheet. Mild cognitive impairment.

PMID- 19741445
TI  - Day 1 multiple organ dysfunction syndrome is associated with poor functional
      outcome and mortality in the pediatric intensive care unit.
AB  - OBJECTIVE: The epidemiology and outcomes of multiple organ dysfunction syndrome
      (MODS) are incompletely characterized in the pediatric population due to small
      sample size and conflicting diagnoses of organ failure. We sought to describe the
      epidemiology and outcomes of early MODS in a large clinical database of pediatric
      intensive care unit (PICU) patients based on consensus definitions of organ
      failure. DESIGN: Retrospective analysis of a contemporaneously collected clinical
      PICU database. SETTING: Virtual Pediatric Intensive Care Unit Performance System
      database patient admissions from January 2004 to December 2005 for 35 U.S.
      children's hospitals. PATIENTS: : We evaluated 63,285 consecutive PICU admissions
      from January 2004 to December 2005 in the Virtual Pediatric Intensive Care Unit
      Performance System database. We excluded patients younger than 1 month or older
      than 18 years of age, and hospitals with >10% missing values for MODS variables.
      We identified day 1 MODS by International Pediatric Sepsis Consensus Conference
      criteria with day 1 laboratory and vital sign values. We evaluated functional
      status using Pediatric Overall Performance Category and Pediatric Cerebral
      Performance Category scores from PICU admission and discharge. INTERVENTIONS: 
      ANALYSIS: Student's t test, chi-square test, Mann-Whitney rank sum, Kruskal
      Wallis, and linear and logistic regression. MEASUREMENTS AND MAIN RESULTS: We
      analyzed 44,693 admissions from 28 hospitals meeting inclusion criteria. Overall
      PICU mortality was 2.8%. We identified day 1 MODS in 18.6% of admissions.
      Patients with day 1 MODS had higher mortality (10.0% vs. 1.2%, p < .001), longer
      PICU length of stay (3.6 vs. 1.3 days, p < .001), and larger change from baseline
      Pediatric Overall Performance Category and Pediatric Cerebral Performance
      Category scores at time of PICU discharge (p < .001). Infants had the highest
      incidence of day 1 MODS (25.2% vs. 16.5%, p < .001) compared with other age
      groups. CONCLUSIONS: Using the largest clinical dataset to date and consensus
      definitions for organ failure, we found that children with MODS present on day 1
      of intensive care unit admission have worse functional outcomes, higher
      mortality, and longer PICU length of stay than children who do not have MODS on
      day 1. Infants are disproportionally affected by MODS.

PMID- 19741447
TI  - A tale of two bridges: effect of the bloodless bridge on renal function and blood
      pressure in neonates managed with venoarterial extracorporeal membrane
      oxygenation.
AB  - OBJECTIVE: To investigate if a change in bridge design of the extracorporeal
      membrane oxygenation (ECMO) circuit had an impact on renal function and blood
      pressure in neonates requiring venoarterial ECMO support. DESIGN: : Retrospective
      chart review. SETTING: A tertiary care neonatal intensive care unit and ECMO
      center. PATIENTS: The medical records of neonates admitted to the neonatal
      intensive care unit and treated with venoarterial ECMO were reviewed. Data were
      collected on 50 consecutive neonates treated previous to (prebridge group) and
      following (postbridge group) transition to a new bridge design on the ECMO
      circuit. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Gestational age,
      gender, racial distribution, and use of hypertensive therapy were similar between
      the two groups. Daily blood urea nitrogen, serum creatinine, urine output, fluid
      balance, and average and maximum systolic and mean arterial blood pressures were
      recorded for the first 3 days on bypass. The postbridge group had lower maximum
      mean arterial blood pressure and systolic blood pressure on day 2 of ECMO and
      lower average mean arterial blood pressure and systolic blood pressure on days 2
      and 3 of ECMO. These differences remained significant after controlling for
      covariates in a multiple regression model. A higher percentage of patients were
      hypertensive (mean arterial blood pressure >60) in the prebridge group compared
      with the postbridge group. There were no differences in blood urea nitrogen,
      serum creatinine, fluid balance, and urine output between the two groups.
      CONCLUSIONS: Patients managed on venoarterial ECMO after the transition to the
      "bloodless" bridge had less hypertension compared with those managed before the
      bridge change. This may reflect improved maintenance of renal perfusion
      associated with transition to an ECMO bridge design that does not require
      intermittent circulation with associated arterial-venous shunting.

PMID- 19741448
TI  - Pediatric in-hospital cardiac arrest and therapeutic hypothermia: where we are
      and where we are going.

PMID- 19741449
TI  - Venous thromboembolism in children: Are we targeting a real or imagined risk?

PMID- 19741450
TI  - Relative risks of recombinant factor VII.

PMID- 19741451
TI  - A picture is worth a thousand words: critical care consultations to emergency
      departments using telemedicine.

PMID- 19741452
TI  - Twenty-three thousand unnecessary deaths every day: what are you doing about it?

PMID- 19741454
TI  - Endoplasmic reticulum stress: an unrecognized actor in solid organ
      transplantation.
AB  - Endoplasmic reticulum (ER) stress is an adaptive response to the accumulation of
      misfolded proteins within the ER, which can trigger cell dedifferentiation and
      cell suicide. Increasing evidences suggest its implication in mediating allograft
      injury. Herein, we summarize the mechanisms of ER stress and discuss its
      implication in allograft injury. Increasing our understanding of the cellular and
      molecular mechanisms of acute and chronic allograft damages could lead to the
      development of new biomarkers and to the discovery of new therapeutic strategies
      to prevent the initiation of graft dysfunction or to promote the tissue
      regeneration after injury.

PMID- 19741455
TI  - Toward MSC in solid organ transplantation: 2008 position paper of the MISOT study
      group.
AB  - The following position paper summarizes the recommendations for early clinical
      trials and ongoing basic research in the field of mesenchymal stem cell-induced
      solid organ graft acceptance--agreed upon on the first meeting of the Mesenchymal
      Stem Cells In Solid Organ Transplantation (MISOT) study group in late 2008.

PMID- 19741456
TI  - Putting objectivity into assessment of steatosis.

PMID- 19741457
TI  - Import pancreas allografts: good from far or far from good?

PMID- 19741458
TI  - Surface modification of islets with PEG-lipid for improvement of graft survival
      in intraportal transplantation.
AB  - BACKGROUND: Transplantation of islets of Langerhans (islets) is a promising
      technique for treating insulin-dependent diabetes mellitus (type I). One unsolved
      issue is the early graft loss due to inflammatory reactions triggered by blood
      coagulation and complement activation that occurs immediately after
      transplantation into the liver through the portal vein. Several proposed
      approaches for improvement of the graft survival include heparin coating and
      covalent poly(ethylene glycol) (PEG) conjugation. We previously have studied the
      improvement of graft survival by modification of islet surfaces using amphiphilic
      PEG-conjugated phospholipid and bioactive molecules. Here, we analyzed the effect
      of PEG-modification on the improvement of graft survival immediately after
      intraportal transplantation into streptozotocin-induced diabetic mice. METHODS:
      The surface of hamster islets was modified with PEG-lipid. PEG-lipid modified
      islets (PEG-islets) were transplanted into the liver through the portal vein of
      streptozotocin-induced diabetic mice. We measured the graft survival periods and
      blood insulin levels immediately after intraportal transplantation to determine
      the cell damage to islets. Histocytochemical analyses of liver were also
      performed postintraportal transplantation. RESULTS: The graft survival of PEG
      islets was significantly prolonged compared with bare islets in livers of
      diabetic mice. Reduction of blood insulin level within 60 min after
      transplantation of PEG-islets suggests that the cell damage observed immediately
      after transplantation could be suppressed by surface modification with PEG in
      comparison with bare islets. CONCLUSION: Our approach for the improvement of
      graft survival will be useful in the clinical setting.

PMID- 19741459
TI  - Impaired effector memory T-cell regulation facilitates graft versus host disease
      in CCR7-deficient bone marrow transplant chimeras.
AB  - BACKGROUND: The development of graft versus host disease (GvHD) is one of the
      major challenges of bone marrow transplantations (BMTs). Although clinical
      symptoms of GvHD share many features with auto immune diseases, the underlying
      mechanisms remain unclear. Here, we examined the effects of hematopoietic CC
      chemokine receptor (CCR)7 deficiency on the development of GvHD. METHODS:
      Lethally irradiated C57BL/6 mice were transplanted with bone marrow cells derived
      from wild-type or CCR7 C57BL/6 donor mice. RESULTS: Unlike littermate controls,
      CCR7 chimeras develop overt GvHD-like symptoms within 6 weeks after
      transplantation. Circulating CD4 and CD8 T-cell populations of CCR7 chimeras were
      enriched in effector memory T cells. CCR7 CD62L regulatory T-cell expansion,
      which typically occurs after BMT was markedly delayed in CCR7 chimeras.
      Furthermore, GvHD-like reactions did not occur after cotransplantation of wild
      type and CCR7 bone marrow, showing that CCR7 is critically required for tolerance
      induction and prevention of GvHD. CONCLUSIONS: We are the first to demonstrate
      that lack of CCR7 results in delayed regulatory T-cell expansion. This results in
      insufficient control of effector memory T-cell expansion, which eventually leads
      to severe tissue damage. Conceivably, therapies aimed at boosting CD4 CD62L
      regulatory T-cell expansion after BMT could help to control GvHD.

PMID- 19741460
TI  - TNF-alpha signaling is not required for in vivo transcriptional reactivation of
      latent murine cytomegalovirus.
AB  - BACKGROUND: Reactivation of cytomegalovirus (CMV) is frequently observed in
      recipients of solid organs and bone marrow transplants and is associated with
      increased risk of acute and chronic allograft rejection, opportunistic infection,
      graft failure, and patient mortality. The molecular mechanisms by which
      reactivation occurs are not well understood. Previous studies have suggested that
      tumor necrosis factor (TNF)-alpha, which is induced by allogeneic
      transplantation, may have a role in reactivation of CMV through activation of
      nuclear factor kappa-light-chain-enhancer of activated B cells and subsequent
      transcriptional reactivation of immediate early (ie) gene expression. METHODS AND
      RESULTS: We have tested the role of TNF-alpha in the reactivation of CMV directly
      by testing whether TNF-alpha is required to initiate transcription of ie gene
      expression in a murine model of allogeneic transplantation of kidneys latently
      infected with mouse CMV. CONCLUSIONS: Our studies show that although TNF-alpha
      seems to be sufficient, it is not required for initiating transcription of ie
      gene expression in this model, suggesting that both TNF-alpha-dependent and 
      independent pathways play an important role in the reactivation of latent CMV
      infection.

PMID- 19741461
TI  - Mammalian target of rapamycin inhibition prevents glomerular hypertrophy in a
      model of renal mass reduction.
AB  - BACKGROUND: Sirolimus (SRL) is a potent and specific immunosuppressive drug used
      in organ transplantation, as basic therapy or in combination with calcineurin
      inhibitors. Although SRL is a nonnephrotoxic drug, many reports have related its
      use with the development of proteinuria, especially after conversion. Therefore,
      the aim of this study was to elucidate the interrelation between early and late
      SRL administration on the development of glomerular hypertrophy and proteinuria
      in a model of renal mass reduction (RMR). METHODS: Rats underwent 2/3
      cryoablation of the left kidney and subsequent right nephrectomy (n=42) or sham
      operations (n=29). Two weeks before (early study) or 12 weeks after (late study)
      surgery, SRL or vehicle was administered three times weekly. Creatinine clearance
      and proteinuria were determined throughout the study, and a complete histologic
      analysis was performed at the end of the study. RESULTS: Treatment with SRL had
      no effect on creatinine clearance, independently of the administration time. Four
      weeks after RMR, a significant increase in proteinuria was observed. Proteinuria
      was stabilized after early and late SRL administration, whereas vehicle-treated
      animals showed a further increase in proteinuria. Glomerular hypertrophy was
      strongly associated with proteinuria, and early SRL introduction prevented
      glomerular enlargement. The histologic analysis showed less structural damage in
      the two groups of animals treated with SRL than in the control group. CONCLUSION:
      Although early SRL introduction blocked glomerular hypertrophy, SRL treatment
      revealed the potential to halt progression of proteinuria and histologic damage
      at any time of administration in a model of RMR.

PMID- 19741462
TI  - Donor HO-1 expression inhibits intimal hyperplasia in unmanipulated graft
      recipients: a potential role for CD8+ T-cell modulation by carbon monoxide.
AB  - BACKGROUND: Induction of heme oxygenase (HO)-1 expression protects transplanted
      organs from humoral rejection and ischemia-reperfusion injury, but induction in
      recipient immune cells also has direct immunomodulatory effects. Although many
      studies have examined the impact of HO-1 after transplantation, it is still
      unclear whether HO-1 expression solely in the donor tissue can influence the
      recipient T-cell response. METHODS: Donor mice were treated with hemin to
      transiently upregulate HO-1. Control or HO-1-expressing aortas were transplanted
      into fully mismatched, completely unmanipulated recipients, and harvested at 6
      weeks to assess neointimal area and T-cell infiltration. T cells were isolated
      from draining lymph nodes to assess cytokine production. In vitro, T-cell
      proliferative and cytokine responses to allogeneic donor dendritic (DC) and
      endothelial cells expressing HO-1 were examined. RESULTS: Neointimal area was
      significantly (P<0.01) reduced in HO-1-expressing grafts. Hemin pretreated
      endothelial cells significantly inhibited proliferation (P<0.01) and interferon
      (IFN)-gamma production (P =0.01) in allogeneic CD8 T cells. This effect was
      mimicked by a carbon monoxide-releasing molecule. No phenotypic or functional
      changes were observed after incubation of T cells with hemin-treated dendritic
      cells. T-cell infiltration of HO-1-expressing donor aortas was significantly
      reduced (P<0.001), but proportions of IFN-gamma-producing T cells harvested from
      regional lymph nodes were similar. CONCLUSIONS: Organs expressing cytoprotective
      HO-1 have a direct influence on the recipient immune response. Given the
      important role of CD8 T cells and IFN-gamma in chronic rejection, these data
      suggest that donor HO-1 expression may be useful to augment other
      immunosuppressive therapies to prolong graft survival and inhibit intimal
      hyperplasia.

PMID- 19741463
TI  - Short-term outcomes for obese live kidney donors and their recipients.
AB  - BACKGROUND: Given the association between obesity and kidney disease, transplant
      professionals have debated the appropriateness of accepting obese live kidney
      donors. We hypothesized that compared with normal weight donors, donors with
      elevated body mass index (BMI) would have (1) more perioperative readmissions and
      reoperations and (2) a greater rise in blood pressure, greater percent rise in
      serum creatinine, and a greater loss of estimated glomerular filtration rate
      after nephrectomy. METHODS: Retrospective cohort study using Organ Procurement
      and Transplantation Network data on live donors who donated kidneys from July 1,
      2004, to December 31, 2005. RESULTS: Nine thousand three hundred nineteen live
      donor kidney transplants were performed. After eliminating donors with missing
      BMI data, 5304 donors were analyzed, among whom 2108 (40.0%) were overweight (25<
      or =BMI<30), 944 (17.8%) were obese (30< or =BMI<35), and 250 (4.7%) were very
      obese (BMI>=35). Readmission and reoperation rates did not differ across donor
      BMI categories. At baseline and at 6 months after nephrectomy, higher BMI was
      associated with higher blood pressure (P<0.01), but changes in systolic blood
      pressure from baseline were similar across BMI categories (P=0.40). At 6 months,
      decline in estimated glomerular filtration rate from baseline (P=0.63) and
      percent change in creatinine (P=0.11) did not differ significantly across groups.
      Delayed graft function was more common among recipients of kidneys from very
      obese donors (odds ratio 2.16, confidence interval 1.20-3.89, P=0.01), but the
      rates of recipient allograft failure and recipient mortality across donor BMI
      groups were similar. CONCLUSION: Short-term follow-up data show good outcomes for
      donors with elevated BMI and their recipients.

PMID- 19741464
TI  - Experience from an active preemptive kidney transplantation program--809 cases
      revisited.
AB  - BACKGROUND: Preemptive kidney transplantation (PKT) is increasingly acknowledged.
      We wanted to investigate the results of an active PKT policy in an unselected end
      stage renal disease population with high prevalence of PKT. METHODS: From 1989 to
      2007, 3400 first kidney transplantations were performed in which 809 were PKTs
      (24%). PKT patients were 7.4 years younger (P<0.001), had more live donors (LD;
      64% vs. 35%, P<0.001), and fewer were panel reactive human leukocyte antigen
      antibody positive (2% vs. 6%, P<0.001). RESULTS: In the Cox regression analyses
      of patient mortality, uncensored and death-censored graft failures, all potential
      risk factors tested were statistically significant, except for recipient sex
      (i.e., recipient and donor age, PKT, deceased donor [DD], diabetes nephropathy,
      human leukocyte antigen-DR mismatch, and panel reactive antibody positivity). For
      patient mortality, PKT and DD had a hazard ratio (HR) of 0.75 (P=0.001) and 1.38
      (P<0.001), respectively. The results were similar for uncensored and death
      censored graft failures. Risk analyses were also performed separately for DD and
      LD cohorts. The results were comparable, except that PKT was not a significant
      risk factor in the LD cohort (HR=0.82, P=0.12 for mortality and HR=0.83, P=0.051
      for uncensored graft failure). However, in DD recipients, patient mortality
      (HR=0.70, P=0.004) and uncensored graft failure (HR=0.68, P<0.001) were
      significantly reduced with PKT. CONCLUSION: PKT reduced the risk of patient
      mortality and uncensored graft failure in DD recipients. Our study confirms the
      advantages of PKT in an unselected end-stage renal disease population with a high
      prevalence of PKT.

PMID- 19741465
TI  - Hyperparathyroidism and vitamin D deficiency predispose to bone loss in renal
      transplant recipients.
AB  - BACKGROUND: Bone disease is common postrenal transplantation resulting in
      increased fracture rates and morbidity. The cause is multifactorial including
      hyperparathyroidism, corticosteroids, and possibly calcium and vitamin D
      deficiencies. The aim of this study was to identify modifiable factors
      contributing to bone disease in long-term renal transplant (RT) recipients.
      METHODS: Ninety-seven RT recipients were prospectively recruited over a 6-month
      period from a single center. Bone-related parameters were collected including
      bone mineral density at lumbar spine and total hip sites, serum and urinary
      markers of bone-turnover and calcium metabolism, and intact parathyroid hormone
      levels. RESULTS: The mean time posttransplant of RT recipients was 9.5 years and
      mean estimated glomerular filtration rate was 70.3 mL/min. Up to 50% of
      recipients had biochemical evidence of calcium and vitamin D deficiencies. In the
      multiple regression models, elevated intact parathyroid hormone levels and
      calcium deficiency, which are affected by estimated glomerular filtration rate
      and vitamin D levels, are significantly associated with reduction in bone mineral
      density measurements. CONCLUSIONS: Hyperparathyroidism and vitamin D deficiency
      are common and are likely to contribute to bone loss postrenal transplantation.
      Measures aim to correct these problems pre- and posttransplant may improve bone
      health in RT recipients.

PMID- 19741466
TI  - Outcomes with conversion from calcineurin inhibitors to sirolimus after renal
      transplantation in the context of steroid withdrawal or steroid continuation.
AB  - BACKGROUND: A number of studies have suggested that conversion from calcineurin
      inhibitors (CNI) to sirolimus (SRL) can improve graft function in renal
      transplant patients. None of these studies has converted patients to SRL in the
      absence of steroids. METHODS: We describe our experience with 278 renal
      transplants of which 153 were converted from CNI to SRL. The majority of patients
      had steroids withdrawn after 6 days. Almost all patients received antithymocyte
      globulin induction and were maintained on mycophenolate mofetil. RESULTS: Six
      months after conversion, patients remaining on SRL therapy had a mean increase in
      estimated glomerular filtration rate of 6.93 mL/min/1.73 m2 (P<0.0001) compared
      with preconversion values. SRL-converted patients analyzed by intention-to-treat
      increased estimated glomerular filtration rate by 5.00 mL/min/1.73 m2 (P=0.0005).
      Eighty-one percent of patients remaining on SRL had a successful conversion,
      defined as stable or improved renal function at 6 months. The only factor
      predictive of unsuccessful conversion was urine protein-to-creatinine ratio more
      than 1. The benefits of SRL conversion were seen in patients at high
      immunological risk as well as those at lower risk. Proteinuria increased by a
      mean of 0.1 (P=0.43) at 6 months. Thirty-six percent of SRL-converted patients
      experienced adverse effects requiring conversion back to CNI. Rates of rejection,
      graft loss, and patient death with SRL conversion were low. CONCLUSIONS: The
      results from our clinical practice suggest that even in the absence of steroids,
      SRL conversion significantly improves renal function, with acceptable rates of
      adverse events.

PMID- 19741467
TI  - Association of common type 2 diabetes risk gene variants and posttransplantation
      diabetes mellitus in renal allograft recipients in Korea.
AB  - BACKGROUND: Posttransplantation diabetes mellitus (PTDM) is a major metabolic
      complication in renal transplant recipients. Recent genome-wide association
      studies have identified several genes associated with type 2 diabetes. Here, we
      examined the association between PTDM and 17 single nucleotide polymorphisms
      (SNPs) located within 15 genes in a cohort of renal allograft recipients in
      Korea. MATERIALS AND METHODS: A total of 589 patients who received kidney
      transplants between 1989 and 2007, without a history of diabetes and had a
      pretransplant fasting glucose less than 5.5 mmol/L were included in this study.
      We analyzed the association between the PTDM development and the following SNPs:
      TCF7L2 rs7903146, SLC30A8 rs13266634, HHEX (rs1111875, rs7923837, and rs5015480),
      CDKAL1 rs10946398, CDKN2A/B rs10811661, IGF2BP2 rs4402960, FTO rs8050136, WFS1
      rs734312, JAZF1 rs864745, CDC123/CAMK1D rs12779790, TSPAN8 rs7961581, THADA
      rs7578597, ADAMTS9 rs4607103, NOTCH2 rs1092391, and KCNQ1 rs2237892. RESULTS:
      Eight SNPs in six genes were significantly associated with the PTDM development:
      TCF7L2 rs7903146 (odds ratio [OR]=2.20, P =0.016), SLC30A8 rs13266634 (OR=1.52, P
      =0.003), HHEX rs1111875 (OR=1.47, P =0.007), HHEX rs7923837 (OR=2.32, P =0.014),
      HHEX rs5015480 (OR=1.59, P =0.003), CDKAL1 rs10946398 (OR=1.43, P =0.008),
      CDKN2A/B rs10811661 (OR=1.33, P =0.039), and KCNQ1 rs2237892 (OR=1.46, P =0.009).
      CONCLUSIONS: These data suggest that genetic variations in TCF7L2, SLC30A8, HHEX,
      CDKAL1, CDKN2A/B, and KCNQ1 are associated with PTDM in Korea.

PMID- 19741468
TI  - Impact of polymorphisms of TLR4/CD14 and TLR3 on acute rejection in kidney
      transplantation.
AB  - BACKGROUND: Organ transplantation itself inevitably activates the innate immune
      system by toll-like receptors (TLRs), potentially leading to allograft rejection
      and graft failure. We evaluated the possible association between the TLR4/CD14
      and TLR3 polymorphisms of donor-recipient pairs, and acute rejection after living
      donor kidney transplantation. METHODS: TLR4 -1607T/C (rs10759932), -2026A/G
      (rs1927914); CD14 -159C/T (rs2569190); and TLR3 rs3775290, rs3775291, and
      rs3775296 were genotyped using DNA samples from 216 donor-recipient pairs of
      adult living donor kidney transplantation between January 1996 and July 2006.
      Dual luciferase reporter assay was performed to determine the functional
      significance of promoter single-nucleotide polymorphisms (SNPs) of TLR4. RESULTS:
      Acute rejection occurred in 42 recipients (19.4%) of 216 adult transplant
      patients within 1 year. The genotype distributions of both recipient and donor
      TLR4 rs10759932 differed significantly between the control (no rejection) and
      acute rejection groups. For recipient rs10759932, the adjusted odds ratio for the
      TC+CC over TT genotype was 0.25 (95% confidence interval, 0.11-0.57; P =0.001).
      When the rs10759932 CC genotype was present in the recipient or donor, no episode
      of acute rejection occurred (Fisher's exact test, P =0.023). The presence of the
      rs10759932 C allele was associated with higher rejection-free survival rates (log
      rank test, P =0.0053). However, there was no difference in transcriptional
      activity between wild-type and variant promoters of TLR4. In contrast to TLR4,
      SNPs of TLR3 or CD14 had no influence on acute rejection. CONCLUSION: These
      findings suggest the importance of TLR4 in the pathogenesis of acute rejection in
      kidney transplantation.

PMID- 19741469
TI  - Recurrent nonhepatic and de novo malignancies after liver transplantation.
AB  - INTRODUCTION: After Liver transplantation (LTx), recurrence of hepatic cancer, de
      novo cancers, and donor-transmitted cancers have been described. However, the
      data for patients with a prior history of nonhepatic malignancy and its
      recurrence post-LTx are limited. AIM: Aim of this study was to examine the
      patient with nonhepatic pre-LTx malignancies, and their recurrence post-LTx along
      with de novo cancers and recurrence of hepatic malignancy in the population.
      PATIENTS AND METHOD: Between March 1996 and July 2006, 1127 patients underwent
      LTx at our institution. Thirty patients (2.7%) (15 men and 15 women, mean age
      56.9+/-12.8 years) had documented nonhepatic malignancies. There were seven
      colorectal, three prostatic, three cervical, three bladder, six breast, and other
      nine miscellaneous cancers (one patient had two cancers). Four patients had
      hepatocellular carcinoma at the time of LTx. All patients were followed up until
      2008 with a mean follow-up period of 34.1+/-35.3 months. RESULTS: One patient
      with oropharyngeal cancer (3.3%), who was recurrence-free pre-LTx for 77.3
      months, developed recurrence 36 months post-LTx and subsequently died 11 months
      postrecurrence. Two patients developed de novo cancer. One developed renal cell
      carcinoma 46.6 months post-LTx and other developed de novo intra-abdominal
      metastatic adenocarcinoma of unknown origin. Three of four patients developed
      recurrent hepatocellular carcinoma. CONCLUSION: The rate of recurrence of
      nonhepatic malignancy was 3% and de novo cancer was 6% in the present series.
      There is a need to develop a guideline for recurrence-free survival period for
      nonhepatic malignancies before LTx, based on the type and stage of cancer.

PMID- 19741470
TI  - Improved outcomes of combined liver and kidney transplants in small children (<15
      kg).
AB  - BACKGROUND: Combined liver and kidney transplantation (CLKT) is a surgical
      challenge in small children because of technical aspects, lack of pediatric
      donors, and restrictions related to the size of the abdominal cavity. We report
      outcomes after CLKT in this challenging group of smaller children. METHOD: A
      review of prospective data on all children undergoing CLKT at the Birmingham
      Children's Hospital between 1994 and 2008 was performed. An analysis of
      perioperative data, complications, and survival in children less than 15 kg was
      carried out, with figures expressed as median (range) and compared with that of
      children more than 15 kg. RESULTS: A total of 23 children underwent CLKT (14 male
      [61%] and age 8.6 [1.6-16.7] years), of which 8 (35%) were less than or equal to
      15 kg, median age 2.2 (1.6-5.4) years, weight 11.6 (9.1-14.9) kg, and height 76
      (66-95) cm, followed up for a median 26 (12-126) months. Donor details included
      age 13 (3-40) years, weight 60 (15-78) kg, and height 156 (83-168) cm. The median
      donor-to-recipient weight ratio was 4.8 compared with 1.7 for larger children.
      The median waiting time was 291 (48-523) compared with 150 (6-455) days for
      children more than 15 kg. Four of eight (50%) children received preoperative
      renal support, when compared with 10 of 16 (62%) children more than 15 kg. The
      intensive care unit and inpatient stay was 2 (2-22) days and 25 (19-93) days,
      respectively. Mortality was seen in one of eight because of sepsis and multiorgan
      failure. When compared with children more than 15 kg, survival figures at 1 and 2
      years were 87% versus 93% and 78%, respectively. CONCLUSIONS: CLKT in small
      children results in comparable outcomes despite challenges related to donor
      recipient size mismatch and longer waiting times. Consequently, body size/stature
      should not be a limiting factor for multiorgan transplantation.

PMID- 19741471
TI  - A rapid and reliable means of assessing hepatic steatosis in vivo via electrical
      bioimpedance.
AB  - BACKGROUND: In liver transplantation, macrovesicular steatosis is a major
      determinant of graft outcome. Visual assessment of steatosis by the donor surgeon
      is highly inaccurate, whereas hepatic biopsy is user dependent and cumbersome.
      Our objective was to validate a novel bioelectrical impedance sensor as a means
      of objectively quantifying macrovesicular hepatic steatosis and to correlate the
      results with another surrogate measure of macrosteatosis, hepatic
      microcirculation. METHODS: Fatty (n=36) and lean (n=18) male Zucker rats, 250 to
      450 g, were used to achieve varying degrees of steatosis. After a bilateral
      subcostal incision, hepatic microcirculation was measured using laser Doppler
      microflowmetry. Low-frequency bioelectrical impedance (LF-BEI) was measured at 1
      kHz using a custom-made sensor and instrumentation system. Complete hepatectomy
      was performed. Hepatic tissue was preserved and stained with hematoxylin-eosin
      for histology. RESULTS AND CONCLUSION: Both microflow and LF-BEI correlated well
      with macrosteatosis and each other: Pearson correlation coefficients -0.71, 0.73,
      and -0.81, respectively. Livers were grouped according to the degree of
      macrosteatosis: mild (<30%), moderate (30%-60%), and severe (>60%). Both LF-BEI
      and microflow varied significantly among groups on one-way analysis of variance,
      although only LF-BEI was capable of discriminating between mild and moderate
      macrosteatosis on post hoc analysis. Regarding their individual capacities to
      detect the presence of severe macrosteatosis, both tests were excellent
      classifiers: receiver operating curve area under the curve 0.885 and 0.9 for LF
      BEI and microflow, respectively. However, the bioimpedance apparatus is more
      rapid and less susceptible to local factors and background noise and could more
      easily be used in the clinical liver transplantation setting.

PMID- 19741472
TI  - No difference in transplant outcomes for local and import pancreas allografts.
AB  - BACKGROUND: In the United States, pancreas allograft allocation is strictly
      regulated. Local centers have the first option to accept an organ, followed by
      regional and national allocation for those not accepted locally. For a pancreas
      to be imported, many centers must have previously rejected the organ for
      transplantation. This study reviews the outcomes of all pancreas allografts
      transplanted at a single center between January 2003 and November 2007. Early
      graft function and graft survival were stratified by geographic source of the
      donor pancreas. METHODS: The records of 247 pancreas recipients and the donors of
      11 imported and discarded pancreas allografts were reviewed. Pancreas allograft
      survival is represented using a Kaplan-Meier survival curve comparing (1) locally
      procured and imported pancreas grafts and (2) grafts procured by a team from our
      own center with the grafts procured by another team. RESULTS: Of the 247 grafts,
      184 (74%) were local and 63 (26%) were imported. There were no differences
      between the two geographic groups in 1-year graft survival (local 91%, import
      90%, P=0.76). Similarly, graft survival was similar regardless of whether the
      organ was procured by our own team or by another center (local team 91%, another
      team 90%, P=0.96). CONCLUSIONS: Pancreas allografts refused by a large number of
      centers may still be imported and successfully transplanted without affecting
      survival results.

PMID- 19741473
TI  - An escalating dose regimen of pegylated interferon and ribavirin in HCV cirrhotic
      patients referred for liver transplant.
AB  - BACKGROUND: To lessen the severity of recurrent hepatitis C virus (HCV) postliver
      transplantation (post-LT) by treating HCV patients with cirrhosis, we assessed
      the safety and efficacy of an escalating dose pegylated interferon (PEG
      IFN)/ribavirin protocol in pre-LT patients. METHODS: Ninety patients were treated
      with 90 microg PEG-IFN alpha-2a and 400 mg ribavirin and advanced to 180 microg
      and 800 to 1200 mg, respectively, over 8 weeks. RESULTS: Mean age was 55.3 years.
      Thirty-four percent of patients received prior interferon treatment, 77% had
      genotype 1 or 4. Mean Child's score was 6.7 and model for end-stage liver disease
      11.2; 49% reached full-dose PEG-IFN and 85% ribavirin, 18% required dose
      reduction, 33% stopped treatment because of adverse effects, 9% had deterioration
      of liver function, and 7% died. Follow-up of 9.6 months showed sustained
      virological response in 13% of patients. The rate of serious complications was
      16.3% in Child's class A, 48% in B, and 100% in C (P=0.005). Serum albumin was a
      significant predictor for worsening liver function (P=0.007). CONCLUSIONS: Using
      an escalating dose regimen of PEG-IFN alpha-2a and ribavirin, we achieved only a
      13% sustained virological response in HCV cirrhotic pre-LT patients with an
      accompanying 9% risk of worsening liver function and 7% risk of death.

PMID- 19741474
TI  - Meta-analysis of medical regimen adherence outcomes in pediatric solid organ
      transplantation.
AB  - BACKGROUND: Adherence to the medical regimen after pediatric organ
      transplantation is important for maximizing good clinical outcomes. However, the
      literature provides inconsistent evidence regarding prevalence and risk factors
      for nonadherence posttransplant. METHODS: A total of 61 studies (30 kidney, 18
      liver, 8 heart, 2 lung/heart-lung, and 3 with mixed recipient samples) were
      included in a meta-analysis. Average rates of nonadherence to six areas of the
      regimen, and correlations of potential risk factors with nonadherence, were
      calculated. RESULTS: Across all types of transplantation, nonadherence to clinic
      appointments and tests was most prevalent, at 12.9 cases per 100 patients per
      year (PPY). The immunosuppression nonadherence rate was six cases per 100 PPY.
      Nonadherence to substance use restrictions, diet, exercise, and other healthcare
      requirements ranged from 0.6 to 8 cases per 100 PPY. Only the rate of
      nonadherence to clinic appointments and tests varied by transplant type: heart
      recipients had the lowest rate (4.6 cases per 100 PPY vs. 12.7-18.8 cases per 100
      PPY in other recipients). Older age of the child, family functioning (greater
      parental distress and lower family cohesion), and the child's psychological
      status (poorer behavioral functioning and greater distress) were among the
      psychosocial characteristics significantly correlated with poorer adherence.
      These correlations were small to modest in size (r=0.12-0.18). CONCLUSIONS: These
      nonadherence rates provide benchmarks for clinicians to use to estimate patient
      risk. The identified psychosocial correlates of nonadherence are potential
      targets for intervention. Future studies should focus on improving the prediction
      of nonadherence risk and on testing interventions to reduce risk.

PMID- 19741475
TI  - Indocyanine green dye excretion in bile reflects graft function after living
      donor liver transplantation.

PMID- 19741476
TI  - The use of inferior epigastric artery in renal transplantation.

PMID- 19741477
TI  - Preliminary results of bilateral arm transplantation.

PMID- 19741478
TI  - HIV-related stigma and psychological distress: the harmful effects of specific
      stigma manifestations in various social settings.
AB  - OBJECTIVES: Recent research has shown that experiences of stigmatization have an
      adverse impact on the psychological well being of people living with HIV/AIDS
      (PLWHA). Most studies investigating this relationship employ an aggregate measure
      of stigma. Although this approach provides useful information about the
      psychological implications of HIV-related stigma in general, it neglects to
      acknowledge the possibility that some manifestations in specific settings may be
      psychologically more detrimental than others. The present study examines which
      specific stigma experiences are most strongly related to psychological distress
      across a number of social settings. METHODS: A cross-sectional survey was
      administered to 667 PLWHA in the Netherlands. We examined participants'
      experiences of 11 manifestations of HIV-related stigma in six social settings.
      Linear regression analyses were conducted to determine which setting-specific
      manifestations best predict psychological distress after controlling for marital
      status, education and health status. RESULTS: Three manifestations in family
      settings, namely receiving advice to conceal one's status, being avoided and
      being treated with exaggerated kindness, and one manifestation in healthcare
      settings, namely awkward social interaction, best predicted psychological
      distress in PLWHA. CONCLUSION: Manifestations of HIV-related stigma vary
      according to setting. Certain manifestations in specific social settings impact
      the psychological well being of PLWHA more than others. In this study, certain
      experiences of stigmatization with PLWHA's families and in healthcare settings
      were more strongly related to psychological distress than experiences occurring
      in other social settings. These findings suggest that stigma reduction
      interventions focusing on these influential settings may benefit the
      psychological well being of PLWHA.

PMID- 19741479
TI  - HIV infection and the risk of cancers with and without a known infectious cause.
AB  - OBJECTIVE: To evaluate the risk of cancers with and without a known infectious
      cause in HIV-infected persons. DESIGN: Retrospective cohort study. METHODS: Adult
      HIV-infected and matched HIV-uninfected members of Kaiser Permanente followed
      between 1996 and 2007 for incident AIDS-defining cancers (ADCs), infection
      related non-AIDS-defining cancers (NADCs; anal squamous cell, vagina/vulva,
      Hodgkin's lymphoma, penis, liver, human papillomavirus-related oral
      cavity/pharynx, stomach) and infection-unrelated NADC (all other NADCs). RESULTS:
      We identified 20 277 HIV-infected and 202 313 HIV-uninfected persons. HIV
      infected persons experienced 552 ADC, 221 infection-related NADC, and 388
      infection-unrelated NADC. HIV-uninfected persons experienced 179 ADC, 284
      infection-related NADC, and 3418 infection-unrelated NADC. The rate ratio
      comparing HIV-infected and HIV-uninfected persons for ADC was 37.7 [95%
      confidence interval (CI): 31.7-44.8], with decreases in the rate ratio over time
      (P < 0.001). The rate ratio for infection-related NADC was 9.2 (95% CI: 7.7
      11.1), also with decreases in the rate ratio over time (P < 0.001). These results
      were largely influenced by anal squamous cell cancer and Hodgkin's lymphoma. The
      rate ratio for infection-unrelated NADC was 1.3 (95% CI: 1.2-1.4), with no change
      in the rate ratio over time (P = 0.44). Among infection-unrelated NADCs, other
      anal, skin, other head and neck, and lung cancer rates were higher and prostate
      cancer rates lower in HIV-infected persons. Among all infection-unrelated NADCs,
      the rate ratio decreased over time only for lung cancer (P = 0.007). CONCLUSION:
      In comparison with those without HIV infection, HIV-infected persons are at
      particular risk for cancers with a known infectious cause, although the higher
      risk has decreased in the antiretroviral therapy era. Cancers without a known
      infectious cause are modestly increased in HIV-infected persons compared with HIV
      uninfected persons.

PMID- 19741480
TI  - Combined antiretroviral therapy is effective on blood plasma HIV-1-RNA: what
      about semen HIV-1-RNA levels?

PMID- 19741481
TI  - Evaluation of a dried blood spot HIV-1 RNA program for early infant diagnosis and
      viral load monitoring at rural and remote healthcare facilities.
AB  - OBJECTIVE: To assess technical and operational performance of a dried blood spot
      (DBS)-based HIV-1 RNA service for remote healthcare facilities in a low-income
      country. DESIGN: A method comparison and operational evaluation of DBS RNA
      against conventional tests for early infant diagnosis of HIV and HIV RNA
      quantitation under field conditions in Tanzania. METHODS: DBSs were prepared and
      plasma was frozen at -80 degrees C. DBSs were mailed and plasma couriered to a
      central laboratory for testing using the Abbott m2000 system. Infant diagnosis
      DBSs were also tested for HIV-1 DNA by ROCHE COBAS AmpliPrep/COBAS TaqMan System.
      Results of DBS RNA were compared with conventional tests; program performance was
      described. RESULTS: Among 176 infant diagnosis participants, using a threshold of
      at least 1000 copies/ml, sensitivity and specificity of DBS versus plasma RNA
      were 1.00 and 0.99, and of DBS RNA versus DBS DNA were 0.97 and 1.00. Among 137
      viral load monitoring participants, when plasma and DBS RNA were compared, r
      value was 0.9709; r value was 0.9675 for at least 5000 copies/ml but was 0.7301
      for less than 5000 copies/ml. The highest plasma RNA value at which DBS RNA was
      not detected was 2084 copies/ml. Median (range) turnaround time from sample
      collection to result receipt at sites was 23 (4-69) days. The Tanzania mail
      service successfully transmitted all DBS and results between sites and the
      central laboratory. CONCLUSION: Under program conditions in Tanzania, DBS
      provided HIV-1 RNA results comparable to conventional methods to remote
      healthcare facilities. DBS RNA testing is an alternative to liquid plasma for HIV
      1 RNA services in remote areas.

PMID- 19741482
TI  - HIV-1 infection of macrophages is dependent on evasion of innate immune cellular
      activation.
AB  - OBJECTIVE: The cellular innate immune response to HIV-1 is poorly characterized.
      In view of HIV-1 tropism for macrophages, which can be activated via pattern
      recognition receptors to trigger antimicrobial defences, we investigated innate
      immune responses to HIV-1 by monocyte-derived macrophages. DESIGN: In a model of
      productive HIV-1 infection, cellular innate immune responses to HIV-1 were
      investigated, at the level of transcription factor activation, specific gene
      expression and genome-wide transcriptional profiling. In addition, the viral
      determinants of macrophage responses and the physiological effect of innate
      immune cellular activation on HIV-1 replication were assessed. RESULTS:
      Productive HIV-1 infection did not activate nuclear factor-kappaB and interferon
      regulatory factor 3 transcription factors or interferon gene expression (IFN) and
      caused remarkably small changes to the host-cell transcriptome, with no evidence
      of inflammatory or IFN signatures. Evasion of IFN induction was not dependent on
      HIV-1 envelope-mediated cellular entry, inhibition by accessory proteins or
      reverse transcription of ssRNA that may reduce innate immune cellular activation
      by viral RNA. Furthermore, IFNbeta priming did not sensitize responses to HIV-1.
      Importantly, exogenous IFNbeta or stimulation with the RNA analogue poly I:C to
      simulate innate immune activation invoked HIV-1 restriction. CONCLUSION: We
      conclude that macrophages lack functional pattern recognition receptors for this
      virus and that HIV-1 tropism for macrophages helps to establish a foothold in the
      host without triggering innate immune cellular activation, which would otherwise
      block viral infection effectively.

PMID- 19741483
TI  - Restoration of the antibody response upon rabies vaccination in HIV-infected
      patients treated with HAART.
AB  - DESIGN: Rabies vaccine was used as a T-cell-dependent neoantigen to investigate
      several aspects of the primary and booster immune response in vivo in HIV
      infected individuals receiving antiretroviral treatment. METHODS: Study
      participants received rabies vaccination twice, within a 3-month interval. Serum
      samples were taken before and 1, 2 and 4 weeks after both vaccinations and 1 and
      5 years after the primary vaccination. Antirabies antibodies [immunoglobulin G
      (IgG), IgG subclasses, immunoglobulin A (IgA) and immunoglobulin M (IgM)] were
      determined; antibody avidity was measured after both vaccinations. T-cell subsets
      were characterized by flow cytometry. RESULTS: Eighteen healthy controls and 30
      HIV-infected adults, treated with HAART for almost 4 years, with a median CD4(+)
      T-cell count of 537 cells/microl, were immunized. The postvaccination
      concentrations of antirabies IgG and IgM were significantly lower in HIV-infected
      individuals as compared with controls. Three T-cell-dependent processes, a true
      booster response, a class switch from IgM to IgG and avidity maturation were
      present in both healthy controls and HIV-infected individuals. Higher age was
      associated with lower postvaccination antirabies IgG and IgM titers. Five years
      after the primary vaccination, 63% of the HIV-infected individuals still had
      antibody titers above the protection threshold. CONCLUSION: Immune restoration in
      HIV-infected individuals treated with HAART, resulting in a CD4(+) T-cell count
      greater than 500 cells/microl, is incomplete. However, the majority of HIV
      infected individuals are capable of mounting a long-lasting immune response,
      including several pivotal T-cell-dependent processes, upon vaccination with a
      neoantigen such as the rabies vaccine.

PMID- 19741484
TI  - Response surface modeling of the interaction between propofol and sevoflurane.
AB  - BACKGROUND: Propofol and sevoflurane display additivity for gamma-aminobutyric
      acid receptor activation, loss of consciousness, and tolerance of skin incision.
      Information about their interaction regarding electroencephalographic suppression
      is unavailable. This study examined this interaction as well as the interaction
      on the probability of tolerance of shake and shout and three noxious stimulations
      by using a response surface methodology. METHODS: Sixty patients preoperatively
      received different combined concentrations of propofol (0-12 microg/ml) and
      sevoflurane (0-3.5 vol.%) according to a crisscross design (274 concentration
      pairs, 3 to 6 per patient). After having reached pseudo-steady state, the authors
      recorded bispectral index, state and response entropy and the response to shake
      and shout, tetanic stimulation, laryngeal mask airway insertion, and
      laryngoscopy. For the analysis of the probability of tolerance by logistic
      regression, a Greco interaction model was used. For the separate analysis of
      bispectral index, state and response entropy suppression, a fractional Emax Greco
      model was used. All calculations were performed with NONMEM V (GloboMax LLC,
      Hanover, MD). RESULTS: Additivity was found for all endpoints, the Ce(50,
      PROP)/Ce(50, SEVO) for bispectral index suppression was 3.68 microg. ml(-1)/ 1.53
      vol.%, for tolerance of shake and shout 2.34 microg . ml(-1)/ 1.03 vol.%, tetanic
      stimulation 5.34 microg . ml(-1)/ 2.11 vol.%, laryngeal mask airway insertion
      5.92 microg. ml(-1) / 2.55 vol.%, and laryngoscopy 6.55 microg. ml(-1)/2.83
      vol.%. CONCLUSION: For both electroencephalographic suppression and tolerance to
      stimulation, the interaction of propofol and sevoflurane was identified as
      additive. The response surface data can be used for more rational dose finding in
      case of sequential and coadministration of propofol and sevoflurane.

PMID- 19741485
TI  - Early phase pharmacokinetics but not pharmacodynamics are influenced by propofol
      infusion rate.
AB  - BACKGROUND: Conventional compartmental pharmacokinetic models wrongly assume
      instantaneous drug mixing in the central compartment, resulting in a flawed
      prediction of drug disposition for the first minutes, and the flaw affects
      pharmacodynamic modeling. This study examined the influence of the administration
      rate and other covariates on early phase kinetics and dynamics of propofol by
      using the enlarged structural pharmacokinetic model. METHODS: Fifty patients were
      randomly assigned to one of five groups to receive 1.2 mg/kg propofol given with
      the rate of 10 to 160 mg . kg(-1). h(-1). Arterial blood samples were taken
      frequently, especially during the first minute. The authors compared four basic
      pharmacokinetic models by using presystemic compartments and the time shift of
      dosing, LAG time. They also examined a sigmoidal maximum possible drug effect
      pharmacodynamic model. Patient characteristics and dose rate were obtained to
      test the model structure. RESULTS: Our final pharmacokinetic model includes two
      conventional compartments enlarged with a LAG time and six presystemic
      compartments and includes following covariates: dose rate for transit rate
      constant, age for LAG time, and weight for central distribution volume. However,
      the equilibration rate constant between central and effect compartments was not
      influenced by infusion rate. CONCLUSIONS: This study found that a combined
      pharmacokinetic-dynamic model consisting of a two-compartmental model with a LAG
      time and presystemic compartments and a sigmoidal maximum possible drug effect
      model accurately described the early phase pharmacology of propofol during
      infusion rate between 10 and 160 mg . kg(-1). h(-1). The infusion rate has an
      influence on kinetics, but not dynamics. Age was a covariate for LAG time.

PMID- 19741486
TI  - A population-based analysis of outpatient colonoscopy in adults assisted by an
      anesthesiologist.
AB  - BACKGROUND: The use of propofol to sedate patients for colonoscopy, generally
      administered by an anesthesiologist in North America, is increasingly popular. In
      the United States, regional use of anesthesiologist-assisted endoscopy appears to
      correlate with local payor policy. This study's objective was to identify
      nonpayor factors (patient, physician, institution) associated with
      anesthesiologist assistance at colonoscopy. METHODS: The authors performed a
      population-based cross-sectional analysis using Ontario health administrative
      data, 1993-2005. All outpatient colonoscopies performed on adults were
      identified. Hierarchical multivariable modeling was used to identify patient
      (age, sex, income quintile, comorbidity), physician (specialty, colonoscopy
      volume), and institution (type, volume) factors associated with receipt of
      anesthesiologist-assisted colonoscopy. RESULTS: During the study period,
      1,838,879 colonoscopies were performed on 1,202,548 patients. The proportion of
      anesthesiologist-assisted colonoscopies rose from 8.4% in 1993 to 19.1% in 2005
      (P < 0.0001). In the hierarchical model, patients in low-volume community
      hospitals were five times more likely to receive anesthesiologist-assisted
      colonoscopy than patients in high-volume community hospitals (odds ration 4.9;
      95% confidence interval 4.4-5.5). Less than 1% of colonoscopies in academic
      hospitals were anesthesiologist-assisted. Compared to gastroenterologists,
      surgeons were more likely to perform anesthesiologist-associated colonoscopy
      (odds ratio 1.7; 95% confidence interval 1.1-2.6). CONCLUSIONS: In Ontario, rates
      of anesthesiologist-assisted colonoscopy have risen dramatically. Institution
      type was most strongly associated with this practice. Further investigation is
      needed to determine the most appropriate criteria for the use of anesthesiology
      services during colonoscopy.

PMID- 19741487
TI  - Tidal volume lower than 6 ml/kg enhances lung protection: role of extracorporeal
      carbon dioxide removal.
AB  - BACKGROUND: Tidal hyperinflation may occur in patients with acute respiratory
      distress syndrome who are ventilated with a tidal volume (VT) of 6 ml/kg of
      predicted body weight develop a plateau pressure (PPLAT) of 28 < or = PPLAT < or
      = 30 cm H2O. The authors verified whether VT lower than 6 ml/kg may enhance lung
      protection and that consequent respiratory acidosis may be managed by
      extracorporeal carbon dioxide removal. METHODS: PPLAT, lung morphology computed
      tomography, and pulmonary inflammatory cytokines (bronchoalveolar lavage) were
      assessed in 32 patients ventilated with a VT of 6 ml/kg. Data are provided as
      mean +/- SD or median and interquartile (25th and 75th percentile) range. In
      patients with 28 < or = PPLAT < or = 30 cm H2O (n = 10), VT was reduced from 6.3
      +/- 0.2 to 4.2 +/- 0.3 ml/kg, and PPLAT decreased from 29.1 +/- 1.2 to 25.0 +/-
      1.2 cm H2O (P < 0.001); consequent respiratory acidosis (Paco2 from 48.4 +/- 8.7
      to 73.6 +/- 11.1 mmHg and pH from 7.36 +/- 0.03 to 7.20 +/- 0.02; P < 0.001) was
      managed by extracorporeal carbon dioxide removal. Lung function, morphology, and
      pulmonary inflammatory cytokines were also assessed after 72 h. RESULTS:
      Extracorporeal assist normalized Paco2 (50.4 +/- 8.2 mmHg) and pH (7.32 +/- 0.03)
      and allowed use of VT lower than 6 ml/kg for 144 (84-168) h. The improvement of
      morphological markers of lung protection and the reduction of pulmonary cytokines
      concentration (P < 0.01) were observed after 72 h of ventilation with VT lower
      than 6 ml/kg. No patient-related complications were observed. CONCLUSIONS: VT
      lower than 6 ml/Kg enhanced lung protection. Respiratory acidosis consequent to
      low VT ventilation was safely and efficiently managed by extracorporeal carbon
      dioxide removal.

PMID- 19741488
TI  - Epidural cooling minimizes spinal cord injury after aortic cross-clamping through
      induction of nitric oxide synthase.
AB  - BACKGROUND: By using a U-shaped lumen catheter, the authors examined the effects
      of epidural cooling on spinal cord injury after aortic cross-clamping (ACC), with
      a focus on changes of spinal cord blood flow and expression of inducible nitric
      oxide synthase. METHODS: Sixteen pigs were randomized into two groups: Control
      group (n = 8) or Cooling group (n = 8). In the latter, epidural cooling started
      at 30 min (baseline) before 45 min of ACC and persisted for the next 30 min of
      reperfusion period. Spinal cord blood flow and somatosensory-evoked potentials
      were assessed during peri-ACC period. At 48 h, we evaluated hind limb function by
      using Tarlov score and expression of inducible nitric oxide synthase on spinal
      cord using immunohistochemistry. RESULTS: After ACC, spinal cord blood flow
      dropped to a similar extent in both groups. During the reperfusion period, spinal
      cord blood flow increased up to 113% (103-124%), median (interquartile range),
      level transiently and decreased to 32% (22-47%) level versus baseline in the
      Control group, whereas it increased and remained at 92% (86-97%) level in the
      Cooling group. Simultaneously, somatosensory-evoked potentials showed that onset
      of loss time was delayed and recovery time was shortened in the Cooling group.
      Tarlov scores in the Cooling group were significantly higher and accompanied by
      normal-appearing motor neurons and significantly greater expression of inducible
      nitric oxide synthase on spinal cord versus the Control group. CONCLUSIONS: This
      study shows that epidural cooling during ACC minimized the risk of spinal cord
      injury, possibly by preventing delayed hypoperfusion and upregulating inducible
      nitric oxide synthase expression.

PMID- 19741489
TI  - Mechanical ventilation induces a Toll/interleukin-1 receptor domain-containing
      adapter-inducing interferon beta-dependent inflammatory response in healthy mice.
AB  - BACKGROUND: Mechanical ventilation (MV) can induce lung injury. Proinflammatory
      cytokines have been shown to play an important role in the development of
      ventilator-induced lung injury. Previously, the authors have shown a role for
      Toll-like receptor 4 signaling. The current study aims to investigate the role of
      Toll/interleukin-1 receptor domain-containing adapter-inducing interferon-beta
      (TRIF), a protein downstream of Toll-like receptors, in the development of the
      inflammatory response after MV in healthy mice. METHODS: Wild-type C57BL6 and
      TRIF mutant mice were mechanically ventilated for 4 h. Lung tissue and plasma was
      used to investigate changes in cytokine profile, leukocyte influx, and nuclear
      factor-kappaB activity. In addition, experiments were performed to assess the
      role of TRIF in changes in cardiopulmonary physiology after MV. RESULTS: MV
      significantly increased messenger RNA expression of interleukin (IL)-1beta in
      wild-type mice, but not in TRIF mutant mice. In lung homogenates, MV increased
      levels of IL-1alpha, IL-1beta, and keratinocyte-derived chemokine in wild-type
      mice. In contrast, in TRIF mutant mice, only a minor increase in IL-1beta and
      keratinocyte-derived chemokine was found after MV. Nuclear factor-kappaB activity
      after MV was significantly lower in TRIF mutant mice compared with wild-type
      mice. In plasma, MV increased levels of IL-6 and keratinocyte-derived chemokine.
      In TRIF mutant mice, no increase of IL-6 was found after MV, and the increase in
      keratinocyte-derived chemokine appeared less pronounced. TRIF deletion did not
      affect cardiopulmonary physiology after MV. CONCLUSIONS: The current study
      supports a prominent role for TRIF in the development of the pulmonary and
      systemic inflammatory response after MV.

PMID- 19741490
TI  - Adaptive support ventilation: an appropriate mechanical ventilation strategy for
      acute respiratory distress syndrome?
AB  - BACKGROUND: Adaptive support ventilation (ASV) allows the clinician to set a
      maximum plateau pressure (PP) and automatically adjusts tidal volume to keep PP
      below the set maximum. METHODS: ASV was compared to a fixed tidal volume of 6
      ml/kg. ASV determined the respiratory rate and tidal volume based on its
      algorithms. Maximum airway pressure limit was 28 cm H2O in ASV. Six sets of lung
      mechanics were simulated for two ideal body weights: 60 kg, Group I; 80 kg, Group
      II. Positive end expiratory pressure was 8, 12, and 16 cm H2O, and target minute
      volume 120%, 150%, and 200% of predicted minute volume. RESULTS: ASV "sacrificed"
      tidal volume and minute ventilation to maintain PP in 9 (17%) of 54 scenarios in
      Group I and 20 (37%) of 54 scenarios in Group II. In Group I, the number of
      scenarios with PP of 28 cm H2O or more was 14 for ASV (26%) and 19 for 6 ml/kg
      (35%). In these scenarios, mean PP were ASV 28.8 +/- 0.86 cm H2O (min 28, max
      30.3) and 6 ml/kg 33.01 +/- 3.48 cm H2O (min 28, max 37.8) (P = 0.000). In group
      II, the number of scenarios PP of 28 cm H2O or more was 10 for ASV (19%) and 21
      for 6 ml/kg (39%). In these cases, mean PP values were ASV 28.78 +/- 0.54 cm H2O
      (min 28, max 29.6) and 6 ml/kg 32.66 +/- 3.37 cm H2O (min 28.2, max 38.2) (P =
      0.000). CONCLUSION: In a lung model with varying mechanics, ASV is better able to
      prevent the potential damaging effects of excessive PP (greater than 28 cm H2O)
      than a fixed tidal volume of 6 ml/kg by automatically adjusting airway pressure,
      resulting in a decreased tidal volume.

PMID- 19741491
TI  - Gamma-amino butyric acid type A receptor mutations at beta2N265 alter etomidate
      efficacy while preserving basal and agonist-dependent activity.
AB  - BACKGROUND: Etomidate acts at gamma-Aminobutyric acid type A (GABAA) receptors
      containing beta2 or beta3, but not beta1 subunits. Mutations at beta residue 265
      (Ser in beta1; Asn in beta2 or beta3) profoundly affect etomidate sensitivity.
      Whether these mutations alter etomidate binding remains uncertain. METHODS:
      Heterologously expressed alpha1beta2gamma2L GABAA receptors and receptors with
      beta2(N265S) or beta2(N265M) mutations were studied electrophysiologically in
      both Xenopus oocytes and HEK293 cells. Experiments quantified the impact of
      beta2N265 mutations or substituting beta1 for beta2 on basal channel activation,
      GABA EC50, maximal GABA efficacy, etomidate-induced leftward shift in GABA
      responses, etomidate direct activation, and rapid macrocurrent kinetics. Results
      were analyzed in the context of an established allosteric co-agonist mechanism.
      RESULTS: Mutations produced only small changes in basal channel activity, GABA
      EC50, maximal GABA efficacy, and macrocurrent kinetics. Relative to wild-type,
      beta2(N265S) reduced etomidate enhancement of apparent GABA affinity six-fold,
      and it reduced etomidate direct activation efficacy 14-fold. beta2(N265M) totally
      eliminated both etomidate modulation of GABA responses and direct channel
      activation. Mechanism-based analysis showed that the function of both mutants
      remains consistent with the allosteric co-agonist model and that beta2(N265S)
      reduced etomidate allosteric efficacy five-fold, whereas etomidate-binding
      affinity dropped threefold. Experiments swapping beta2 subunits for beta1
      indicated that etomidate efficacy is reduced 34-fold, whereas binding affinity
      drops less than two-fold. CONCLUSIONS: Mutations at beta2N265 profoundly alter
      etomidate sensitivity with only small changes in basal and GABA-dependent channel
      activity. Mutations at the beta2N265 residue or replacement of beta2 with beta1
      influence etomidate efficacy much more than binding to inactive receptors.

PMID- 19741492
TI  - Epidural analgesia in the latent phase of labor and the risk of cesarean
      delivery: a five-year randomized controlled trial.
AB  - BACKGROUND: The optimal timing of epidural analgesia has been a controversial
      issue, and how early women can benefit from epidural analgesia is still debated.
      The objective of this trial was to test the hypothesis that patient-controlled
      epidural analgesia given at cervical dilation of 1.0 cm or more does not increase
      the risk of prolonged labor or Cesarean delivery. METHODS: After institutional
      review board approval and patient consent, 12,793 nulliparous patients requesting
      neuraxial analgesia were enrolled and randomized to an early epidural (cervical
      dilation at least 1.0 cm) or delayed epidural (cervical dilation at least 4.0 cm)
      group. A 15-ml epidural analgesic mixture consisting of 0.125% (1.25 mg/ml)
      ropivacaine plus 0.3 microg/ml sufentanil was given in a single bolus, followed
      by patient-controlled pump with a 10-ml bolus without background infusion.
      Repeatable meperidine (25 mg) was prescribed as being the rescue analgesic to
      patients in the delayed epidural group. The primary outcome was the rate of
      Cesarean section. RESULTS: The median diameters of cervical dilation were 1.6 cm
      and 5.1 cm in the early and delayed epidural groups, respectively (P < 0.0001).
      The duration of labor from analgesia request to vaginal delivery was equal in
      both groups (11.3 +/- 4.5 h for early epidural and 11.8 +/- 4.9 h for delayed
      epidural group women, P = 0.90). No statistically significant difference in the
      rate of Cesarean section was observed between the two groups on the intention-to
      treat analysis (23.2% vs. 22.8% in the early and delayed epidural groups,
      respectively; P = 0.51). CONCLUSIONS: Epidural analgesia in the latent phase of
      labor at cervical dilation of 1.0 cm or more does not prolong the progression of
      labor and does not increase the rate of Cesarean in nulliparous women compared
      with the delayed analgesia at the cervical dilation of 4.0 cm or more.

PMID- 19741493
TI  - Amnestic concentrations of etomidate modulate GABAA,slow synaptic inhibition in
      hippocampus.
AB  - BACKGROUND: Gamma-aminobutyric acid type A (GABA(A)) receptor-mediated inhibition
      in the central nervous system exists in two forms: phasic (inhibitory
      postsynaptic currents, IPSCs) and tonic (nonsynaptic). Phasic inhibition is
      further subdivided into fast (GABA(A,fast)) and slow (GABA(A,slow)) IPSCs. By
      virtue of its dendritic location and kinetics, GABA(A,slow) has been proposed to
      control synaptic plasticity and memory. Etomidate is a nonbarbiturate,
      intravenous anesthetic that selectively modulates GABA(A) receptors and produces
      amnesia at low doses in vivo. This study tested whether correspondingly low
      concentrations of etomidate in vitro alter GABA(A,fast) and GABA(A,slow) phasic
      inhibition. METHODS: Electrophysiological recordings were obtained from
      hippocampal slices prepared from postnatal day 3-8 mice and maintained in
      organotypic culture for 10-14 days. Etomidate was applied at concentrations
      corresponding to one-half to four times the half maximal effective concentration
      that impairs hippocampus-dependent learning and memory--i.e., 0.125-1.0 microm.
      RESULTS: Etomidate 0.25 microm (the half maximal effective concentration) doubled
      the time constant of decay of GABA(A,slow) IPSCs, but it had no detectable effect
      on GABA(A,fast) IPSCs. Higher concentrations of etomidate had stronger effects on
      both types of phasic inhibition: 0.5 and 1 microm etomidate prolonged the time
      constant of decay by 310% and 410% for GABA(A,slow) and by 25% and 78% for
      GABA(A,fast). Concentrations of etomidate up to 1 microm had no significant
      effects on the amplitudes of either GABA(A,fast) or GABA(A,slow) IPSCs.
      CONCLUSIONS: At concentrations that impair hippocampus-dependent memory,
      etomidate modulates GABA(A,slow) more strongly than GABA(A,fast) IPSCs. Effects
      of etomidate on GABA(A,slow) IPSCs may contribute to etomidate-induced amnesia.

PMID- 19741494
TI  - Hemodynamic effects of ephedrine, phenylephrine, and the coadministration of
      phenylephrine with oxytocin during spinal anesthesia for elective cesarean
      delivery.
AB  - BACKGROUND: Hemodynamic responses to vasopressors used during spinal anesthesia
      for elective Cesarean delivery, have not been well described. This study compared
      the effects of bolus phenylephrine and ephedrine on maternal cardiac output (CO).
      The hypothesis was that phenylephrine, but not ephedrine, decreases CO when
      administered in response to hypotension during spinal anesthesia. METHODS: Forty
      three patients were randomized to receive 80 microg of phenylephrine or 10 mg of
      ephedrine. Both pulse wave form analysis and transthoracic bioimpedance changes
      were used to estimate stroke volume in each patient. Hemodynamic responses to
      spinal anesthesia and oxytocin were also recorded. A subgroup of 20 patients was
      randomized to receive oxytocin compared with oxytocin plus 80 microg of
      phenylephrine after delivery. RESULTS: Mean CO and maximum absolute response in
      CO were significantly lower during the 150 s after phenylephrine administration
      than after ephedrine (6.2 vs. 8.1 l/min, P = 0.001, and 5.2 vs. 9.0 l/min, P <
      0.0001, respectively for pulse wave form analysis, and 5.2 vs. 6.3 l/min, P =
      0.01 and 4.5 vs. 6.7 l/min, P = 0.0001, respectively for bioimpedance changes).
      CO changes correlated with heart rate changes. Coadministration of phenylephrine
      obtunded oxytocin-induced decreases in systemic vascular resistance and increases
      in heart rate and CO. Trends in CO change were similar using either monitor.
      CONCLUSIONS: Bolus phenylephrine reduced maternal CO, and decreased CO when
      compared with ephedrine during elective spinal anesthesia for Cesarean delivery.
      CO changes correlated with heart rate changes after vasopressor administration,
      emphasizing the importance of heart rate as a surrogate indicator of CO.
      Coadministered phenylephrine obtunded hemodynamic responses to oxytocin.

PMID- 19741495
TI  - S(+)-ketamine effect on experimental pain and cardiac output: a population
      pharmacokinetic-pharmacodynamic modeling study in healthy volunteers.
AB  - BACKGROUND: Low-dose ketamine behaves as an analgesic in the treatment of acute
      and chronic pain. To further understand ketamine's therapeutic profile, the
      authors performed a population pharmacokinetic-pharmacodynamic analysis of the
      S(+)-ketamine analgesic and nonanalgesic effects in healthy volunteers. METHODS:
      Ten men and ten women received a 2-h S(+)-ketamine infusion. The infusion was
      increased at 40 ng/ml per 15 min to reach a maximum of 320 ng/ml. The following
      measurements were made: arterial plasma S(+)-ketamine and S(+)-norketamine
      concentrations, heat pain intensity, electrical pain tolerance, drug high, and
      cardiac output. The data were modeled by using sigmoid Emax models of S(+)
      ketamine concentration versus effect and S(+)-ketamine + S(+)-norketamine
      concentrations versus effect. RESULTS: Sex differences observed were restricted
      to pharmacokinetic model parameters, with a 20% greater elimination clearance of
      S(+)-ketamine and S(+)-norketamine in women resulting in higher drug plasma
      concentrations in men. S(+)-ketamine produced profound drug high and analgesia
      with six times greater potency in the heat pain than the electrical pain test.
      After ketamine-infusion, analgesia rapidly dissipated; in the heat pain test but
      not the electrical pain test, analgesia was followed by a period of hyperalgesia.
      Over the dose range tested, ketamine produced a 40-50% increase in cardiac
      output. A significant consistent contribution of S(+)-norketamine to overall
      effect was detected for none of the outcome parameters. CONCLUSIONS: S(+)
      ketamine displays clinically relevant sex differences in its pharmacokinetics. It
      is a potent analgesic at already low plasma concentrations, but it is associated
      with intense side effects.

PMID- 19741496
TI  - Fluoroscopic observation of the occipitoatlantoaxial complex during intubation
      attempt in a rheumatoid patient with severe atlantoaxial subluxation.

PMID- 19741498
TI  - Uncalibrated stroke volume variations are able to predict the hemodynamic effects
      of positive end-expiratory pressure in patients with acute lung injury or acute
      respiratory distress syndrome after liver transplantation.
AB  - BACKGROUND: Positive end-expiratory pressure (PEEP) may reduce cardiac output and
      total hepatic blood flow after liver transplantation. Pulse pressure variation is
      useful in predicting the PEEP-induced decrease in cardiac output. The aim of the
      study was to examine the relationships between stroke volume variations (SVV)
      obtained with the Vigileo monitor (Edwards Lifesciences, Irvine, CA), and the
      hemodynamic effects of PEEP. METHODS: Over 2 yr, patients presenting an acute
      lung injury or an acute respiratory distress syndrome in the 72 h after liver
      transplantation were prospectively enrolled. Patients were monitored with a
      pulmonary artery catheter (stroke volume) and with the Vigileo system (stroke
      volume and SVV). Measurements were performed in duplicate, first during zero end
      expiratory pressure and then 10 min after the addition of 10 cm H2O PEEP.
      RESULTS: Twenty-six patients were included. Six patients were excluded from
      analysis. On PEEP, SVV and pulse pressure variation increased significantly and
      stroke volume decreased significantly. PEEP-induced changes in stroke volume
      measured by pulmonary artery catheter were significantly correlated with SVV (r =
      0.69; P < 0.001) and pulse pressure variation on zero end-expiratory pressure (r
      = 0.66, P < 0.001). PEEP-induced decrease in stroke volume measured by pulmonary
      artery catheter > or = 15% was predicted by an SVV > 7% (sensitivity = 100%,
      specificity = 80%) and by a pulse pressure variation > 8% (sensitivity = 80%,
      specificity = 100%). PEEP-induced changes in stroke volume measured by pulmonary
      artery catheter and Vigileo device were correlated (r = 0.51, P < 0.005).
      CONCLUSIONS: SVV obtained with Vigileo monitor is useful to predict decrease in
      stroke volume induced by PEEP. Moreover, this device is able to track changes in
      stroke volume induced by PEEP.

PMID- 19741497
TI  - Nitrous oxide plus isoflurane induces apoptosis and increases beta-amyloid
      protein levels.
AB  - BACKGROUND: Some anesthetics have been suggested to induce neurotoxicity,
      including promotion of Alzheimer's disease neuropathogenesis. Nitrous oxide and
      isoflurane are common anesthetics. The authors set out to assess the effects of
      nitrous oxide and/or isoflurane on apoptosis and beta-amyloid (Abeta) levels in
      H4 human neuroglioma cells and primary neurons from naive mice. METHODS: The
      cells or neurons were exposed to 70% nitrous oxide and/or 1% isoflurane for 6 h.
      The cells or neurons and conditioned media were harvested at the end of the
      treatment. Caspase-3 activation, apoptosis, processing of amyloid precursor
      protein, and Abeta levels were determined. RESULTS: Treatment with a combination
      of 70% nitrous oxide and 1% isoflurane for 6 h induced caspase-3 activation and
      apoptosis in H4 naive cells and primary neurons from naive mice. The 70% nitrous
      oxide plus 1% isoflurane, but neither alone, for 6 h induced caspase-3 activation
      and apoptosis, and increased levels of beta-site amyloid precursor protein
      cleaving enzyme and Abeta in H4-amyloid precursor protein cells. In addition, the
      nitrous oxide plus isoflurane-induced Abeta generation was reduced by a broad
      caspase inhibitor, Z-VAD. Finally, the nitrous oxide plus isoflurane-induced
      caspase-3 activation was attenuated by gamma-secretase inhibitor L-685,458, but
      potentiated by exogenously added Abeta. CONCLUSION: These results suggest that
      the common anesthetics nitrous oxide plus isoflurane may promote neurotoxicity by
      inducing apoptosis and increasing Abeta levels. The generated Abeta may further
      potentiate apoptosis to form another round of apoptosis and Abeta generation.
      More studies, especially the in vivo confirmation of these in vitro findings, are
      needed.

PMID- 19741499
TI  - Response of serum proteome in patients undergoing infrarenal aortic aneurysm
      repair.
AB  - BACKGROUND: Postoperative organ dysfunction in conventional surgery for abdominal
      aortic aneurysm (AAA) is associated with a complex inflammatory reaction, with
      activation of coagulation and fibrinolysis. A prospective,observational study was
      performed to define the complex plasma proteomic changes after AAA repair and to
      identify factor(s) that may affect myocardial function in uncomplicated
      procedures. METHODS: Ten patients undergoing infrarenal AAA repair were
      investigated. Eight subjects subjected to major abdominal surgery served as
      controls. Hemodynamic changes were continuously monitored by using the pressure
      recording analytical method technique. The time course of plasma proteins was
      investigated after induction of anesthesia and at different times after surgery
      (6 h, 12 h, 24 h, 36 h) by using two-dimensional difference gel electrophoresis,
      matrix-assisted laser desorption/ionization-time of flight mass spectrometry, and
      Western blot. The effects of plasma on the functional properties of isolated rat
      ventricular myocytes were also investigated. RESULTS: In AAA patients alone, 18
      spots were found to change more than two-fold in expression level, spot
      identification revealing an increased thrombin generation 6 h after surgery. At
      the same time cardiac cycle efficiency significantly reduced versus baseline (
      0.5 +/- 0.9 vs. 0.18 +/- 0.3 in AAA patients, P < 0.01; 0.4 +/- 0.1 vs. 0.2 +/-
      0.3 in control surgery, not significant; P < 0.01 group x time interaction at
      ANOVA). Plasma obtained 6 h after AAA surgery dose-dependently inhibited
      contractile function of control rat myocytes (percent shortening fell by 51% with
      10% of AAA plasma and was abolished with 20% of AAA plasma, P < 0.001 for both).
      The inhibitory response was abolished by thrombin antagonism. CONCLUSIONS: These
      findings show for the first time the possible role of thrombin generation within
      the complex activation of inflammatory response in causing hemodynamic
      instability in the early postoperative period after AAA surgery.

PMID- 19741500
TI  - Basal forebrain histaminergic transmission modulates electroencephalographic
      activity and emergence from isoflurane anesthesia.
AB  - BACKGROUND: The tuberomammillary histaminergic neurons are involved in the
      sedative component of anesthetic action. The nucleus basalis magnocellularis
      (NBM) in the basal forebrain receives dense excitatory innervation from the
      tuberomammillary nucleus and is recognized as an important site of sleep-wake
      regulation. This study investigated whether NBM administration of histaminergic
      drugs may modulate arousal/emergence from isoflurane anesthesia. METHODS:
      Microinjections of histaminergic agonists and antagonists were made into the NBM
      of rats anesthetized with isoflurane. The changes in electroencephalographic
      activity, including electroencephalographic burst suppression ratio and power
      spectra, as well as respiratory rate, were recorded under basal conditions and
      after NBM injection. Time to resumption of righting reflex was recorded as a
      measure of emergence from anesthesia. RESULTS: The rats displayed a burst
      suppression electroencephalographic pattern at inhaled isoflurane concentrations
      of 1.4-2.1%. Application of histamine (1 microg/0.5 microl) to the NBM reversed
      the electroencephalographic depressant effect of isoflurane; i.e.,
      electroencephalographic activity shifted from the burst suppression pattern
      toward delta activity at 1.4% isoflurane, and the burst suppression ratio
      decreased at 2.1% isoflurane. Histamine-evoked activation of
      electroencephalography was blocked by NBM pretreatment with a H1 receptor
      antagonist, triprolidine (5 microg/1 microl), but not by a H2 receptor
      antagonist, cimetidine (25 microg/1 microl). The respiratory rate was
      significantly increased after histamine injection. NBM application of histamine
      facilitated, while triprolidine delayed, emergence from isoflurane anesthesia.
      CONCLUSIONS: Histamine activation of H1 receptors in the NBM induces
      electroencephalographic arousal and facilitates emergence from isoflurane
      anesthesia. The basal forebrain histaminergic pathway appears to play a role in
      modulating arousal/emergence from anesthesia.

PMID- 19741503
TI  - Anticancer activity and mechanisms of diacetyldianhydrogalactitol on hepatoma QGY
      7703 cells.
AB  - Diacetyldianhydrogalactitol (DADAG) is a member of the hexitols which shows a
      significant anticancer effect. Despite the fact that the antitumor effects of
      DADAG have been studied in a number of cell lines, the mechanism of its action
      remains unclear. Herein, we explored antitumor effects of DADAG and the possible
      mechanisms by which it inhibited the growth of human hepatocellular carcinoma
      cell QGY-7,703 and its derived xenograft tumors. Cell proliferation was evaluated
      with the sulforhodamine B assay in vitro. The results suggested that DADAG had
      mild antiproliferative activity on QGY-7,703 cells. The antitumor effect of DADAG
      was assessed in nude mice xenografted with QGY-7,703 cells. We found that DADAG
      significantly inhibited the tumor growth. Flow cytometry results indicated that
      the retarded cell proliferation is associated with increased G2/M cell cycle
      arrest. Further studies showed that the induced G2/M cell cycle arrest is, at
      least partially, attributed to an upregulation of cyclin B1, phospho-cell
      division cycle 2 (cdc2) (Thr), phospho-cdc2 (Thr), and cdc25c protein expression,
      and a decrease in cdc2 protein expression. Taken together, our data show that
      DADAG has mild proliferative effects on QGY-7,703 cells in vitro, but it
      significantly inhibits the growth of QGY-7,703 in a xenograft model in vivo. The
      modulation of several cell cycle progression regulation proteins responsible for
      G2/M phase transition may account for its antitumor effects.

PMID- 19741502
TI  - Docetaxel first-line therapy in HER2-negative advanced breast cancer: a cohort
      study in patients with prospectively determined HER2 status.
AB  - Docetaxel is one of the most active cytotoxic drugs against breast cancer, but
      data are lacking on specific activity in molecularly selected subgroups. This
      retrospective study was aimed at assessing the outcome and prognostic factors for
      survival of patients with HER2-negative tumors receiving first-line docetaxel
      based chemotherapy for advanced breast cancer (ABC). The medical charts of all
      162 patients with prospectively proven HER2-negative ABC and having received
      docetaxel as first-line chemotherapy for metastatic disease at our institution
      were retrospectively reviewed with special emphasis on docetaxel efficacy.
      Potential prognostic factors were sought using multivariate analysis. Median
      progression-free survival (PFS) was 12 months (95% confidence interval 9.7-14.8)
      and median overall survival (OS) was 34.9 months (95% confidence interval 28.1
      52.1). Hormone receptor (HR) status was the strongest prognostic factor in the
      univariate analysis for both PFS [hazard ratio = 0.23; P = 0.00000063] and OS
      (hazard ratio = 0.35; P = 0.0000079). After multivariate analysis, only three
      independent variables for PFS (HR-positive tumor, no prior adjuvant/neoadjuvant
      chemotherapy, and isolated bone metastases) and two for OS (HR-positive tumor and
      isolated bone metastases) remained predictive of a favorable outcome. HER2
      negative, HR-positive ABC patients have a relatively good prognostic after
      docetaxel-containing first-line therapy. The subset of HER2-negative, HR-negative
      (triple-negative) has a very poor outcome, and innovative therapies are eagerly
      awaited for these patients.

PMID- 19741501
TI  - Adenosine: an old drug newly discovered.
AB  - Over decades, anesthesiologists have used intravenous adenosine as mainstay
      therapy for diagnosing or treating supraventricular tachycardia in the
      perioperative setting. More recently, specific adenosine receptor therapeutics or
      gene-targeted mice deficient in extracellular adenosine production or individual
      adenosine receptors became available. These models enabled physicians and
      scientists to learn more about the biologic functions of extracellular nucleotide
      metabolism and adenosine signaling. Such functions include specific signaling
      effects through adenosine receptors expressed by many mammalian tissues; for
      example, vascular endothelia, myocytes, hepatocytes, intestinal epithelia, or
      immune cells. At present, pharmacological approaches to modulate extracellular
      adenosine signaling are evaluated for their potential use in perioperative
      medicine, including attenuation of acute lung injury; renal, intestinal, hepatic
      and myocardial ischemia; or vascular leakage. If these laboratory studies can be
      translated into clinical practice, adenosine receptor-based therapeutics may
      become an integral pharmacological component of daily anesthesiology practice.

PMID- 19741504
TI  - Preclinical assessment of cisplatin-based therapy versus docetaxel-based therapy
      on a panel of human non-small-cell lung cancer xenografts.
AB  - The success of treatment of advanced non-small-cell lung cancer (NSCLC) remains
      very poor. The aim of this study was, on a series of NSCLC xenografts, to compare
      the efficacy of standard cisplatin-based or docetaxel-based chemotherapy. Seven
      human xenografts were obtained from six patients (two xenografts were derived
      from primary or metastatic tumors of the same patient). Three xenografts were
      adenocarcinomas and four were squamous cell carcinomas. All xenografts reproduced
      the same histology as that of the patient's original tumor. Docetaxel,
      administered as single-agent chemotherapy, induced a significant response in five
      of the seven NSCLC xenografts (71%), without significant increase after
      combination with cisplatin, vinorelbine, or gemcitabine. Relative expression of
      genes putatively involved in drug response was also studied in all xenografts and
      did not explain the variability of drug sensitivity. In conclusion, this panel of
      human NSCLC xenografts reliably reproduces the data obtained in patient tumors
      and the relative sensitivity to docetaxel reported in NSCLC patients.

PMID- 19741505
TI  - The involvement of nicotinic receptor subtypes in the locomotor activity and
      analgesia induced by methamphetamine in mice.
AB  - We have previously reported that methamphetamine (METH) interacts with nicotinic
      acetylcholine receptor (nAChR) subtypes. This study investigated the involvement
      of nAChR in the effects of METH locomotion and pain. Chronic, but not acute,
      nicotine pretreatment potentiated METH-induced hyperlocomotion. This potentiation
      was abolished by pretreatment with methyllycaconitine, an antagonist of alpha
      7nAChR, or dihydrobetaerythroidine, an antagonist of alpha-4/beta-2nAChR. The
      mechanism by which amphetamines induce analgesia is not well understood. We
      investigated the analgesic effects of METH in the writhing, hot-plate and
      formalin tests and found that methyllycaconitine antagonized METH-induced
      analgesia in the writhing and formalin tests but not in the hot-plate test.
      Conversely, dihydrobetaerythroidine was only effective in the hot-plate test. We
      conclude that alpha-7nAChR activation by METH is involved in the analgesic
      effects induced by METH at both spinal and supraspinal levels, whereas METH
      activation of alpha-4/beta-2nAChR is responsible for the analgesic effect
      elicited at the supraspinal level. These results show that nAChRs are involved in
      several actions of amphetamine derivatives and are an important target for the
      pharmacology of these drugs of abuse.

PMID- 19741506
TI  - The ampakine, Org 26576, bolsters early spatial reference learning and retrieval
      in the Morris water maze: a subchronic, dose-ranging study in rats.
AB  - Ampakines have shown beneficial effects on cognition in selected animal models of
      learning. However, their ability to modify long-term spatial memory tasks has not
      been studied yet. This would lend credence to their possible value in treating
      disorders of cognition. We evaluated the actions of subchronic Org 26576
      administration on spatial reference memory performance in the 5-day Morris water
      maze task in male Sprague-Dawley rats, at doses of 1, 3 and 10 mg/kg twice daily
      through intraperitoneal injection over 12 days. Org 26576 exerted a dose and time
      dependent effect on spatial learning, with dosages of 3 and 10 mg/kg
      significantly enhancing acquisition on day 1. Globally, escape latency decreased
      significantly as the training days progressed in the saline and Org 26576-treated
      groups, indicating that significant and equal learning had taken place over the
      learning period. However, at the end of the learning period, all doses of Org
      26576 significantly improved spatial memory storage/retrieval without confounding
      effects in the cued version of the task. Org 26576 offers early phase spatial
      memory benefits in rats, but particularly enhances search accuracy during
      reference memory retrieval. These results support its possible utility in
      treating disorders characterized by deficits in cognitive performance.

PMID- 19741507
TI  - Impaired endothelial function may be due to decreased aortic tetrahydrobiopterin,
      assessed by a new flow-mediated vasodilation in vivo in
      hypercholesterolemic/atherogenic mice.
AB  - Tetrahydrobiopterin (BH4) is an important cofactor for endothelial nitric oxide
      synthase activity. The relationship between endothelial function in vivo and
      aortic BH4 level is not fully understood, however. In the present study, we aimed
      to clarify whether reduction of aortic BH4 levels contributes to endothelial
      dysfunction in vivo using spontaneously hyperlipidemic mice. To estimate
      endothelial function in vivo and in real-time state, we developed a flow-mediated
      vasodilation (FMV) method in mice, which measured changes in the diameter of the
      femoral artery in response to increased blood flow. C57BL/6 mice and apoE/low
      density lipoprotein receptor double knock-out mice were fed a low-fat diet (LFD)
      or a high-fat diet (HFD) for 12 weeks from 6 weeks of age. HFD feeding impaired
      FMV in double knock-out mice, but not in C57BL/6 mice. Furthermore, HFD feeding
      reduced plasma NOx concentration and aortic BH4 level in double knock-out mice.
      Conversely, exogenous injection of BH4 (2 mg/kg) markedly increased aortic BH4
      levels and restored endothelial function. In conclusion, we demonstrated that HFD
      feeding impaired nitric oxide-mediated endothelial function and reduced BH4 level
      in vivo, and that acute augmentation of aortic BH4 levels improved endothelial
      function. These findings indicate that BH4 is a critical determinant of nitric
      oxide-mediated endothelial function in hypercholesterolemia.

PMID- 19741508
TI  - Management of major bleedings during anticoagulant treatment with the oral direct
      thrombin inhibitor ximelagatran or warfarin.
AB  - Several new oral anticoagulants are currently investigated in phase III
      programmes, mainly with inhibition of factor Xa or thrombin as their
      pharmacological target. Advantages are expected with these new drugs compared
      with vitamin K antagonists, but one potential drawback is the lack of specific
      antidotes. During the clinical studies with ximelagatran, an oral direct thrombin
      inhibitor withdrawn due to hepatic side effects, investigators were instructed to
      manage bleedings with routine measures. We have retrospectively tried to assess
      whether this was sufficient or whether there was a need for reversal strategies.
      The study population consisted of patients with major bleedings in three long
      term studies (104 ximelagatran, 155 warfarin). All individual patient narratives
      were reviewed with respect to management of the bleeding. Complementary data were
      retrieved from the data-based case report forms. Approximately, two of three of
      the patients in both groups were subject to some kind of treatment. One-third
      (1/3) in both groups had transfusions documented and/or received specific
      medication. Vitamin K was given more often to warfarin patients. Two ximelagatran
      patients received prothrombin complex (four-factor concentrate), but one was a
      patient with a severe hepatopathy suspected to be drug-induced. Overall, the case
      descriptions did not reveal any apparent differences in the course of events
      between groups. We found no indications that the lack of an antidote posed a
      clinical problem in patients treated with ximelagatran as compared with warfarin.
      The relatively short half-life of melagatran, the active metabolite of
      ximelagatran, may have contributed to these results.

PMID- 19741509
TI  - The influence of low-dose aspirin and hydroxyurea on platelet-leukocyte
      interactions in patients with essential thrombocythemia.
AB  - Essential thrombocythemia is associated with an increased risk of thromboembolic
      complications. Recently, there has been a growing evidence that platelet
      leukocyte interactions may contribute to pathogenesis of thrombosis in essential
      thrombocythemia. Low-dose aspirin (ASA) is generally recommended in the therapy
      of low-risk patients for thrombosis, whereas hydroxyurea in high-risk patients.
      The aim of the present study was to determine the effect of ASA and hydroxyurea
      on platelet, leukocyte functions and on formation of platelet/leukocyte
      conjugates in vivo in patients with essential thrombocythemia. Markers of
      platelet and leukocyte activation were assessed in 40 patients with essential
      thrombocythemia at diagnosis and in 20 controls using flow cytometry assays. In
      second part of the study, the tests were repeated after either ASA treatment (in
      25 low-risk patients) or hydroxyurea therapy (in 15 high-risk patients). On
      diagnosis, significantly elevated expression of P-selectin on platelets (4.98 +/-
      3.31 vs. 0.99 +/- 0.69 P < 0.001) and increased percentage of platelet
      polymorphonuclear leukocyte CD11b/CD42b conjugates [10.12 (4.21-31.22) vs. 3.17
      (1.43-5.99) P < 0.001] and platelet-monocyte CD11b/CD14/CD61 conjugates [36.62
      (12.23-51.62) vs. 13.86 (7.14-23.51) P < 0.001] were found in essential
      thrombocythemia group as compared with the healthy control group. Therapy with
      ASA significantly reduced platelet-polymorphonuclear leukocyte [10.72 (4.21
      26.97) vs. 8.12 (1.13-26.94) P < 0.05] and platelet-monocyte conjugates [38.6
      (13.45-51.62) vs. 25.76 (13.52-45.02) P < 0.05]. Surprisingly, therapy with
      hydroxyurea was poorly effective in reduction of platelet/leukocyte conjugates.
      These data document an increased platelet and leukocyte activation at the time of
      diagnosis. This is the first report showing enhanced platelet-leukocyte aggregate
      formation in low-risk essential thrombocythemia patients and the efficacy of ASA
      in its reduction.

PMID- 19741510
TI  - Simultaneous validation of the SunTech 247 diagnostic station blood pressure
      measurement device according to the British Hypertension Society protocol, the
      International Protocol and the Association for the Advancement of Medical
      Instrumentation standards.
AB  - OBJECTIVE: SunTech 247 is an oscillometric blood pressure (BP) monitor
      manufactured by SunTech Medical Inc., Morrisville, North Carolina, USA. The aims
      of this study were (i) to determine its accuracy using the 1993 modified British
      Hypertension Society (BHS) protocol, the 2002 International Protocol (IP) and the
      2002/2003 Association for the Advancement of Medical Instrumentation (AAMI)
      standards, (ii) to compare the performance of BHS protocol and IP. METHODS:
      Systolic BP (SBP) and diastolic BP (DBP) were recorded to the nearest 2 mmHg and
      measured with the arm supported at heart level. For each participant, nine
      sequential same arm measurements were taken by two trained observers, comparing
      the device to standard mercury sphygmomanometers. Procedures and data analysis
      were carried out following protocols guidelines. RESULTS: First, we recruited 33
      participants required by the IP. Then, data collection continued to obtain 85
      participants for the BHS protocol/AAMI standard. Readings differing by less than
      5, 10 and 15 mmHg for SBP and DBP fulfilled IP recommendations. According to the
      BHS protocol, for the better observer, the percentage of test device readings
      differing from the mercury standard by 5, 10 and 15 mmHg or less were: 92.9, 100
      and 100% for SBP and 94.9, 98.8 and 99.6% for DBP. The mean differences +/-
      standard deviation between the device and mercury sphygmomanometer readings were
      1.7 +/- 3.1 mmHg for SBP and 1.1 +/- 3.2 mmHg for DBP, achieving AAMI
      requirements. Standard deviation of mean differences were 2.4 for SBP and 2.1 for
      DBP, following the IP, and 3.1 and 3.2, respectively, for BHS protocol. The
      variance of all 99 differences (total deviance), with 98 degree of freedom, was
      585.6 for SBP and 444.1 for DBP. The 33 differences obtained from the mean
      differences for each participant (between-subject variance), with 32 degree of
      freedom, were 275.6 and 152.1, respectively. F test was 1.83 with P = 0.0191 for
      SBP, and 1.07 (P = 0.3936) for DBP. CONCLUSION: (i) The device achieved the
      requirements stated by the 2002 IP, fulfilled the standards stated by the AAMI,
      and on the basis of the standards indicated by the 1993 modified BHS protocol,
      can be classified as 'A' grade both for SBP and DBP. Therefore, SunTech 247 may
      be recommended for clinical use, (ii) IP and BHS protocol provide complementary
      features for device validation; the comparison of total deviance and between
      subject variance confirms the estimates of IP authors for SBP.

PMID- 19741511
TI  - Medical students, intellectual curiosity, and algorithmic medicine: reflections
      of a teacher.

PMID- 19741512
TI  - Prediction of left ventricular dysfunction progression in patients with a first
      ST-elevation myocardial infarction--contribution of cystatin C assessment.
AB  - OBJECTIVES: Left ventricular (LV) dysfunction is a major cause of poor outcome
      after myocardial infarction. We sought to investigate the factors that might
      contribute to the prediction of postinfarct LV dysfunction progression, and
      whether the addition of cystatin C (CystC) to this assessment might be useful.
      METHODS: NT-proBNP, CRP, CystC, and troponin I were measured in 150 patients with
      a first ST-elevation myocardial infarction (STEMI) who were followed up for 6
      months. Echocardiography was performed at discharge and follow-up. RESULTS: In
      multivariable logistic regression, LV ejection fraction decrease at follow-up
      exceeding 0.2 was independently predicted by CRP [odds ratio (OR): 1.09, 95%
      confidence interval (CI): 1.05-1.13, P<0.0001], multivessel disease (OR: 8.83,
      95% CI: 4.01-19.41, P<0.001), and left anterior descending artery involvement
      (OR: 5.09, 95% CI: 1.60-16.22, P<0.006); whereas peak early diastolic mitral flow
      velocity to peak early diastolic mitral annular velocity ratio (E/E') exceeding
      15 indicating elevated LV filling pressure by CystC (OR: 3.53, 95% CI: 1.11
      11.26, P<0.01), diabetes (OR: 4.04, 95% CI: 1.58-10.58, P<0.005), and multivessel
      disease (OR: 4.09, 95% CI: 1.52-11.05, P<0.006). CRP, NT-proBNP, and CystC were
      among the independent determinants of clinical outcomes (heart failure
      hospitalizations, mortality, and recurrent ischemic events). Receiver operator
      characteristic analyses identified CRP being the most valuable in discriminating
      LV ejection fraction decrease exceeding 0.2 and CystC in discriminating E/E'
      exceeding 15. CONCLUSION: Using multiple biomarkers may contribute to the better
      prediction of LV dysfunction progression and the risk of adverse cardiac events
      in patients with STEMI. CystC may improve this evaluation, especially with regard
      to the development of echocardiographic features of elevated LV filling pressure.

PMID- 19741513
TI  - Calories and cachexia.
AB  - PURPOSE OF REVIEW: Anorexia and weight loss are associated with increased
      mortality in cachectic patients. The role of caloric supplementation is
      controversial. The purpose of this review is to examine the role of calorie
      supplementation in cachexia. RECENT FINDINGS: Caloric supplementation improves
      outcomes in malnourished hospital patients and malnourished older persons. It may
      improve the quality of life in cancer patients and for those persons receiving
      palliative care. Caloric supplementation should include a balanced essential
      amino acid supplement given at least twice a day. The role of eicosapentanoic
      acid as a supplement is controversial. All caloric supplements should be given
      between and not with meals. SUMMARY: Caloric supplementation rich in protein and
      with adequate vitamin D should be given between meals to all patients with
      cachexia.

PMID- 19741514
TI  - Can the use of creatine supplementation attenuate muscle loss in cachexia and
      wasting?
AB  - PURPOSE OF REVIEW: Weight loss and low BMI due to an underlying illness have been
      associated with increased mortality, reduced functional capacity, and diminished
      quality of life. There is a need for well tolerated, long-term approaches to
      maintain body weight in patients with cachexia or wasting. The purpose of this
      review is to highlight the scientific and clinical evidence derived from the
      recent literature investigating the rationale for and potential medical use of
      creatine supplementation in patients with cachexia or wasting. RECENT FINDINGS:
      Some studies have demonstrated that supplementation with creatine can increase
      creatine reserves in skeletal muscle and increase muscle mass and performance in
      various disease states that affect muscle size and function. The mechanisms
      underlying these effects are not clear. It has been suggested that creatine
      supplementation may increase intramuscular phosphocreatine stores and promote
      more rapid recovery of adenosine triphosphate levels following exercise, thus
      allowing users to exercise for longer periods or at higher intensity levels.
      Other hypothesized mechanisms include attenuation of proinflammatory cytokines,
      stimulation of satellite cell proliferation and upregulation of genes that
      promote protein synthesis and cell repair. SUMMARY: Creatine is a generally well
      tolerated, low-cost, over-the-counter nutritional supplement that shows potential
      in improving lean body mass and functionality in patients with wasting diseases.
      However, placebo-controlled studies have shown variable effects, with
      improvements in some and not in others. Additional studies with longer follow-up
      are required to identify the populations that might benefit most from creatine
      supplementation.

PMID- 19741515
TI  - Effects of inflammation and/or inactivity on the need for dietary protein.
AB  - PURPOSE OF REVIEW: Protein requirement in healthy young and old individuals is
      traditionally defined as the lowest protein intake sufficient to achieve neutral
      body protein balance. This concept, however, cannot be applied to those
      conditions characterized by unavoidable protein catabolism despite optimal
      nutrition, such as inactivity and diseases associated with systemic inflammation.
      RECENT FINDINGS: The ability of dietary proteins to promote protein anabolism is
      reduced by inactivity and inflammatory mediators, whereas physical exercise
      ameliorates the efficiency in using dietary proteins. Consequently, the protein
      intake level associated with the lowest rate of catabolism in inactivity and/or
      inflammation is greater than the minimum protein intake required to achieve
      neutral protein balance in healthy, physically active individuals. A protein
      intake of 1.2 g.kg.day is currently recommended for inactive healthy individuals,
      whereas guidelines recommend up to 1.5 g.kg.day in patients with severe systemic
      inflammation, such as those affected by critical illness or cancer. High protein
      intake accelerates progression of renal insufficiency but does not affect renal
      function in healthy individuals. SUMMARY: In inflammation and/or inactivity a
      relatively high protein intake may be required to promote synthesis of specific
      proteins, prevent depletion of selected amino acids (e.g., glutamine or
      arginine), modulate immune functions, counteract insulin resistance and redox
      unbalance. Thus, an optimal protein/amino acid intake may be greater than that
      required to decrease whole body protein wasting.

PMID- 19741516
TI  - The role of beta-adrenoceptor signaling in skeletal muscle: therapeutic
      implications for muscle wasting disorders.
AB  - PURPOSE OF REVIEW: The beta-adrenergic signaling pathway represents a novel
      therapeutic target for skeletal muscle wasting disorders due to its roles in
      regulating protein synthesis and degradation. beta-Adrenoceptor agonists (beta
      agonists) have therapeutic potential for attenuating muscle wasting associated
      with sarcopenia (age-related muscle wasting), cancer cachexia, sepsis, disuse,
      burns, HIV-AIDS, chronic kidney or heart failure, and neuromuscular diseases such
      as the muscular dystrophies. This review describes the role of beta-adrenergic
      signaling in the mechanisms controlling muscle wasting due to its effects on
      protein synthesis, protein degradation, and muscle fiber phenotype. RECENT
      FINDINGS: Stimulation of the beta-adrenergic signaling pathway with beta-agonists
      has therapeutic potential for muscle wasting since administration can elicit an
      anabolic response in skeletal muscle. As a consequence of their potent muscle
      anabolic actions, the effects of beta-agonist administration have been examined
      in several animal models and human conditions of muscle wasting in the hope of
      discovering a new therapeutic. The repartitioning characteristics of beta
      agonists (increasing muscle mass and decreasing fat mass) have also made them
      attractive anabolic agents for use in livestock and by some athletes. However,
      potentially deleterious cardiovascular side-effects of beta-agonists have been
      identified and these will need to be obviated in order for the therapeutic
      potential of beta-agonists to be realized. SUMMARY: Multiple studies have
      identified anticachectic effects of beta-agonists and their therapeutic potential
      for pathologic states when muscle protein hypercatabolism is indicated. Future
      studies examining beta-agonist administration for muscle wasting conditions need
      to separate beneficial effects on skeletal muscle from potentially deleterious
      effects on the heart and cardiovascular system.

PMID- 19741517
TI  - Targeting the vaginal microbiota with probiotics as a means to counteract
      infections.
AB  - PURPOSE OF REVIEW: The microbial composition of the vagina of healthy and
      infected women is becoming more fully elucidated with molecular techniques. The
      purpose of this review is to examine our current understanding of the vaginal
      microbiota and assess how probiotic bacteria might reduce infectivity. RECENT
      FINDINGS: It appears that there are some remarkable similarities in the bacterial
      species that inhabit the vagina of women from diverse ethnic backgrounds. Yet,
      distinct outliers exist in which a small portion of apparently healthy women have
      extremely complex microbiota, whereas most have a relatively simple microbiota.
      Bacterial vaginosis is the most common aberrant condition in women, yet its
      pathogenesis is poorly understood and it is often asymptomatic. Vulvovaginal
      candidiasis is better known, yet many women self-treat with antifungals when in
      fact they have bacterial vaginosis. Urinary tract infection (UTI) remains
      extremely common, with no real breakthrough treatment or prevention strategy
      developed in the past 30 or more years. The ability of lactobacilli probiotic
      interventions to prevent, treat and improve the cure of these infections has long
      been considered and is now supported by some clinical evidence. SUMMARY: The
      mechanisms whereby certain probiotic lactobacilli improve urogenital health
      include immune modulation, pathogen displacement and creation of a niche less
      conducive to proliferation of pathogens and their virulence factors. Probiotics
      offer a potential new means to prevent urogenital infections and help maintain a
      healthy vaginal ecosystem.

PMID- 19741518
TI  - Functional food for pregnant, lactating women and in perinatal nutrition: a role
      for dietary fibres?
AB  - PURPOSE OF REVIEW: If the benefits of dietary fibre in healthy adults have
      extensively been studied, little information is available on the specific needs
      of pregnant, lactating women or foetus. As far as infants are concerned, milk
      oligosaccharides are supposed to be the optimal 'dietary fibre'. The
      supplementation of infant formula with prebiotic oligosaccharides is still
      discussed. However, recent studies provide a large amount of information,
      allowing a new discussion on this topic. RECENT FINDINGS: Most recent findings
      are linked to the involvement of dietary fibre in occurrence or prevention of
      obesity. The multiple mechanisms appear more clearly than earlier. This finding
      will soon allow appropriate counselling for young mothers at risk of obesity
      and/or postpartum retention weight, gestational diabetes and preeclampsia.
      Another area which benefits from recent research is the use of prebiotics in
      formula. SUMMARY: Pregnancy is a critical period during which many physiologic
      changes occurred and is associated with several gut disorders and metabolic
      diseases. Dietary fibre may be helpful in the prevention and management of these
      diseases. Lactation and pregnancy are two phases during which food consumption of
      the mother can interact with the physiology of the baby. Moreover, the use of
      formula supplemented in oligosaccharides is able to compensate for the lack of
      some of the complex molecules naturally present in human milk.

PMID- 19741519
TI  - Muscle atrophy in cachexia: can dietary protein tip the balance?
AB  - PURPOSE OF REVIEW: To review the efficacy of dietary protein supplementation in
      attenuating muscle atrophy in cachexia. RECENT FINDINGS: Only very few recent
      randomized controlled trials have studied the effects of protein supplementation
      in clinical cachexia. It appears that supplementation of dietary protein (>1.5
      g/kg per day) alone or in combination with other anabolic stimuli such as
      exercise training maintains or even improves muscle mass, but results on muscle
      function are controversial and no clinical studies have yet directly linked
      alterations in cellular signaling or metabolic signatures of protein intake
      induced muscle anabolism to muscle weight gain. SUMMARY: To elucidate the role of
      dietary protein supplementation in attenuating muscle atrophy in cachectic
      patients, randomized clinical trials are needed in adequately phenotyped patients
      using sensitive measures of muscle mass and function.

PMID- 19741520
TI  - Emerging therapies in traumatic hemorrhage control.
AB  - PURPOSE OF REVIEW: Care of the injured patient is a dynamic process. Hemorrhage
      remains the primary cause of preventable death after trauma. Rapid and effective
      early care can improve survival and outcomes. Emerging therapies to address
      traumatic hemorrhage will be discussed. RECENT FINDINGS: Current concepts in
      trauma care include damage control resuscitation with rapid surgical correction
      of bleeding; prevention of the development of the lethal triad; limitation of
      crystalloid administration and application of high ratios of plasma and platelets
      to packed red blood cells. Prehospital resuscitation strategies can effect care
      of the hemorrhaging trauma patient, as well. The goal should be to preserve vital
      functions without increasing the risk for further bleeding. The concept of
      hypotensive resuscitation has been formulated to address this issue. The type of
      resuscitation fluid also plays an important role, with novel fluids currently
      being studied for routine use. Compressible hemorrhage constitutes an important
      component of potentially survivable injury. Hemostatic dressings and tourniquets
      can prove essential to the management of combat and civilian wounds. SUMMARY:
      Given the potential to preserve life with appropriate attention applied to the
      bleeding trauma victim, it is vitally important to explore the options currently
      available and continue to make improvements in care.

PMID- 19741521
TI  - Traumatic brain injury.
AB  - PURPOSE OF REVIEW: To illustrate how recent international initiatives, supported
      by the National Institutes of Health (NIH) and the Department of Defense, have
      helped us better understand different aspects of traumatic brain injury (TBI),
      including the contribution of primary blast overpressure to mild TBI and post
      traumatic stress disorder. A broad effort is gaining momentum to unravel reasons
      behind failed therapeutic trials in TBI. RECENT FINDINGS: Heterogeneity seems to
      be one fundamental barrier to successful therapeutic trials in TBI. To compensate
      for heterogeneity, multiple workgroups were assigned to approach the problem. The
      International Mission for Prognosis and Clinical Trial design database was
      generated and used as a medium to adjust for multiple covariates. In addition,
      sliding dichotomy and proportional odds were applied to statistical methodology
      in order to improve power calculations. The conference report of Margulies and
      Hicks proposed combination therapies to add synergy to treatment effects. In
      October 2007, a workgroup was assigned by the NIH to work on a novel
      multidimensional classification of TBI, one with a strong pathoanatomical,
      pathophysiological, and functional congruity. As two international randomized
      trials on decompressive craniectomy approach completion, an outburst of class II
      and III studies suggest that this simple surgical procedure may change our future
      outlook on management of severe head injury. SUMMARY: Well designed, targeted,
      combination therapies based on multidimensional classification of TBI may result
      in better appreciation of treatment effects in future randomized controlled
      trials.

PMID- 19741522
TI  - Role of interleukins in the regulation of basophil development and secretion.
AB  - PURPOSE OF REVIEW: It is well appreciated that differentiation, growth, and
      function of basophils are regulated by a network of cytokines, and that these
      cells express a unique composition of surface receptors including interleukin
      binding sites. In the current article, most recent discoveries around cytokine
      regulation of basophils are discussed and compared with previous data. RECENT
      FINDINGS: Confirming previous studies, the most potent growth factor for
      basophils remains interleukin (IL)-3, followed by granulocyte-macrophage colony
      stimulating factor and IL-5. These cytokines also act on mature basophils through
      specific receptors, thereby mediating adhesion, migration, and releasability.
      Other molecules regulating basophil function are chemokines such as IL-8 or
      eotaxin and IL-33. Especially IL-33 has been described as a novel basophil
      regulator. All cytokines act on basophils via specific receptors and signal
      transduction pathways. The present article provides a summary of our knowledge on
      cytokine regulation of basophils and receptor expression, with emphasis on most
      recent developments in the field. SUMMARY: Basophil regulation by cytokines in
      health and disease may be a more complex process than has been considered
      previously. Some of the affected cytokine cascades, receptors, and signal
      transduction molecules may serve as targets of therapy in 'basophil activation
      disorders' in the future.

PMID- 19741523
TI  - Neutropenia in type Ib glycogen storage disease.
AB  - PURPOSE OF REVIEW: Glycogen storage disease type Ib, characterized by disturbed
      glucose homeostasis, neutropenia, and neutrophil dysfunction, is caused by a
      deficiency in a ubiquitously expressed glucose-6-phosphate transporter (G6PT).
      G6PT translocates glucose-6-phosphate (G6P) from the cytoplasm into the lumen of
      the endoplasmic reticulum, in which it is hydrolyzed to glucose either by a
      liver/kidney/intestine-restricted glucose-6-phosphatase-alpha (G6Pase-alpha) or
      by a ubiquitously expressed G6Pase-beta. The role of the G6PT/G6Pase-alpha
      complex is well established and readily explains why G6PT disruptions disturb
      interprandial blood glucose homeostasis. However, the basis for neutropenia and
      neutrophil dysfunction in glycogen storage disease type Ib is poorly understood.
      Recent studies that are now starting to unveil the mechanisms are presented in
      this review. RECENT FINDINGS: Characterization of G6Pase-beta and generation of
      mice lacking either G6PT or G6Pase-beta have shown that neutrophils express the
      G6PT/G6Pase-beta complex capable of producing endogenous glucose. Loss of G6PT
      activity leads to enhanced endoplasmic reticulum stress, oxidative stress, and
      apoptosis that underlie neutropenia and neutrophil dysfunction in glycogen
      storage disease type Ib. SUMMARY: Neutrophil function is intimately linked to the
      regulation of glucose and G6P metabolism by the G6PT/G6Pase-beta complex.
      Understanding the molecular mechanisms that govern energy homeostasis in
      neutrophils has revealed a previously unrecognized pathway of intracellular G6P
      metabolism in neutrophils.

PMID- 19741524
TI  - Antifungal drug resistance: do molecular methods provide a way forward?
AB  - PURPOSE OF REVIEW: Antifungal drug resistance is a confounding factor that
      negatively impacts clinical outcome for patients with serious mycoses. Early
      detection of fungi in blood or other specimens with a rapid assessment of drug
      susceptibility could improve the survival of patients with invasive disease by
      accelerating the initiation of appropriate antifungal treatment. Recent years
      have seen the growth of molecular technology that is ideally suited for fungal
      identification and assessment of drug resistance mechanisms. RECENT FINDINGS:
      Elucidation of the genetic mechanisms responsible for triazole and echinocandin
      resistance in prominent Candida spp. and Aspergillus spp. provides an opportunity
      to develop molecular diagnostic platforms suitable for rapid detection of primary
      and secondary drug resistance. Several highly dynamic and robust
      amplification/detection methodologies are now available that can provide
      simultaneous species identification and high fidelity discrimination of
      resistance alleles. SUMMARY: Molecular diagnostic platforms are ideal for rapid
      detection of fungal pathogens and they provide an opportunity to develop in
      parallel molecular assays that can evaluate antifungal drug resistance.

PMID- 19741526
TI  - Pregnancy in women suffering from familial hypercholesterolemia: a harmful period
      for both mother and newborn?
AB  - PURPOSE OF REVIEW: The present review aims to highlight the consequences for
      mother and child of profound hypercholesterolemia during pregnancy of women with
      familial hypercholesterolemia. RECENT FINDINGS: Familial hypercholesterolemia is
      increasingly diagnosed in younger patients due to the existence of screening
      programs and more widespread cholesterol testing. Increasing numbers of young
      female patients with familial hypercholesterolemia raise the issue of pregnancy
      and its consequences for the familial hypercholesterolemia patient herself but
      also for her offspring. When pregnancy is considered, lipid-lowering drugs are
      often discontinued because of the fear for teratogenic effects. The evidence for
      teratogenesis associated with statin use is scant and conflicting. On the other
      hand, several studies do suggest that pronounced hypercholesterolemia during
      pregnancy has adverse effects on both fetus and mother. In fact, human and animal
      studies reveal an enhanced tendency toward atherosclerosis in the offspring of
      women who suffer from hypercholesterolemia during pregnancy. In animal studies,
      some evidence exists that this can be reversed by treatment with lipid-lowering
      and antioxidative agents. Until today, however, no human studies exist that have
      evaluated efficacy or safety of lipid-lowering interventions in pregnant women
      with familial hypercholesterolemia. SUMMARY: Altogether, the suggested
      relationship between severe hypercholesterolemia and enhanced atherosclerosis in
      offspring and possibly the mother warrants further confirmation and,
      consequently, studies that focus on therapeutic strategies that can safely lower
      cholesterol levels during pregnancy in these women.

PMID- 19741525
TI  - Pediatric antifungal agents.
AB  - PURPOSE OF REVIEW: In immunocompromised hosts, invasive fungal infections are
      common and fatal. In the past decade, the antifungal armamentarium against
      invasive mycoses has expanded greatly. The purpose of the present report is to
      review the most recent literature addressing the use of antifungal agents in
      children. RECENT FINDINGS: Most studies evaluating the safety and efficacy of
      antifungal agents are limited to adults. However, important progress has been
      made in describing the pharmacokinetics and safety of newer antifungal agents in
      children, including the echinocandins. SUMMARY: Dosage guidelines for newer
      antifungal agents are currently based on adult and limited pediatric data.
      Because important developmental pharmacology changes occur throughout childhood
      impacting the pharmacokinetics of these agents, antifungal studies specifically
      designed for children are necessary.

PMID- 19741527
TI  - Primary central nervous system lymphoma.
AB  - PURPOSE OF REVIEW: This review will summarize recent advances in the
      understanding and treatment of primary central nervous system lymphoma (PCNSL).
      RECENT FINDINGS: The molecular and genetic characteristics that distinguish PCNSL
      are beginning to be elucidated. New tools such as flow cytometry and PET are
      improving the diagnosis and management of PCNSL. Although the current standard of
      care is high-dose methotrexate-based chemotherapy alone or in combination with
      whole brain radiotherapy, multiple questions remain regarding the optimal
      treatment of PCNSL, in general, and unusual variants of PCNSL. SUMMARY: Although
      recent advances have improved our understanding of PCNSL, the need for additional
      collaborative research is critical.

PMID- 19741528
TI  - Novel insights into the pathogenesis of gliomas based on large-scale molecular
      profiling approaches.
AB  - PURPOSE OF REVIEW: To review recent advances in brain tumor research based on the
      application of large-scale molecular profiling approaches, in particular
      concerning their impact on the understanding of glioma pathogenesis as well as
      their role in glioma diagnostics and therapy. RECENT FINDINGS: The search for new
      cancer genes as well as the generation of tumor-specific genomic, epigenetic and
      transcriptional profiles has been advanced by the application of genome-wide
      array-based profiling and large-scale sequencing efforts. Recent studies
      employing these techniques added in complementing the picture of the alterations
      and pathways most frequently involved in gliomagenesis and thus qualifying as
      promising targets for glioma diagnostics and therapy. Moreover, these approaches
      identified novel aberrations, for example, mutations in the isocitrate
      dehydrogenase 1 and 2 genes (IDH1, IDH2) and duplication/fusion of the BRAF
      oncogene, which are of diagnostic and prognostic importance in glioma patients.
      In addition, the discovery of genetic alterations that convey treatment
      resistence, such as MSH6 mutations, will contribute to enforce patient selection
      for more individualized therapies. SUMMARY: This brief review highlights selected
      large-scale molecular profiling studies published within the last year that
      significantly advanced our knowledge of the molecular biology of human gliomas
      and contributed novel glioma biomarkers of clinical interest.

PMID- 19741529
TI  - The neural basis of constraint-induced movement therapy.
AB  - PURPOSE OF REVIEW: This review describes our current understanding of the changes
      in brain function and structure that occur in response to an intensive form of
      motor rehabilitation, constraint-induced movement therapy (CIMT), that has been
      shown to be efficacious in promoting motor function of the paretic upper limb of
      stroke patients. RECENT FINDINGS: Studies using transcranial magnetic stimulation
      have demonstrated consistently an increase in the size of the representation of
      paretic hand muscles in the ipsilesional motor cortex after CIMT. This motor map
      expansion occurs in response to CIMT delivered at all time periods after stroke,
      from within days to after several years. Functional neuroimaging studies have
      shown varying patterns of change in activation within the sensorimotor network
      after CIMT. This variability may depend on the extent of stroke-induced damage to
      the corticospinal tract, the major descending motor pathway in the brain. This
      variability may also stem from interacting plastic changes in brain structure
      occurring in response to CIMT. SUMMARY: CIMT is the first well defined poststroke
      motor rehabilitation to have identified changes in brain function and structure
      that accompany gains in motor function of the paretic upper limb. However, a
      causal link between observed changes in brain function/structure and motor gains
      due to CIMT has not yet been established. There is still much work to be done to
      understand the relationship between changes in brain function/structure and gains
      in motor function. Such studies should employ rigorous experimental controls to
      enable strong conclusions to be drawn regarding the neural effects of CIMT and
      how those effects confer behavioral efficacy of the therapy.

PMID- 19741530
TI  - Management of cervical spondylotic myelopathy with insights from metabolic
      imaging of the spinal cord and brain.
AB  - PURPOSE OF REVIEW: Cervical spondylotic myelopathy (CSM) is a potentially
      debilitating disorder primarily related to spinal cord injury caused by
      degenerative changes of the spine. As the population continues to age and live
      longer, it is likely that this disorder will be encountered with increasing
      frequency. RECENT FINDINGS: Surgical management continues to be a mainstay of
      treatment of CSM patients, but some studies have indicated that nonoperative
      treatment may be equivalent to surgical management in some patients. Recent
      advances in neuroimaging of the spinal cord and brain have provided novel
      information regarding the pathogenesis of CSM, as well as compensatory mechanisms
      to preserve neurological function. SUMMARY: CSM is a complex disorder whose
      incidence is likely to increase in coming years. Prospective, randomized studies
      are required to help establish the optimal treatment paradigm. Recent advances
      such as novel neuroimaging techniques and the continued development of neural
      repair strategies to treat the secondary biological injury associated with this
      disorder are likely to play key roles in the future management of CSM.

PMID- 19741531
TI  - Pharmacology and treatment of neuropathic pains.
AB  - PURPOSE OF REVIEW: This review briefly discusses the definition and clinical
      presentation of neuropathic pain and highlights recent advances in the treatment
      of neuropathic pain. RECENT FINDINGS: Recent publications have confirmed the
      efficacy of tricyclic antidepressants, gabapentin, pregabalin, opioids, and
      tramadol for various neuropathic pain conditions. Selective serotonin
      noradrenaline reuptake inhibitors have been found to reduce pain in painful
      neuropathy. The new anticonvulsant lacosamide may have some effect in painful
      polyneuropathy, whereas levetiracetam has failed to relieve postmastectomy and
      spinal cord injury pain. The role of the old anticonvulsant phenytoin is still
      unsettled. A recent trial has found an effect of cannabinoids also in peripheral
      neuropathic pain. Various topical treatments such as topical lidocaine, topically
      applied capsaicin in high concentrations (8%), and botulinum toxin have recently
      been shown to have a pain-relieving effect in various peripheral neuropathic pain
      conditions. Spinal cord and transcranial magnetic stimulation are stimulation
      therapies with some evidence for efficacy. SUMMARY: Treating neuropathic pain
      remains a great challenge, and the treatment has to be individualized to the
      single patient, taking into account side effects, pain type, comorbidities, and
      drug interactions.

PMID- 19741532
TI  - Adenovirus infections in solid organ transplant recipients.
AB  - PURPOSE OF REVIEW: Adenoviruses are emerging as important viral pathogens in
      solid organ transplant recipients, impacting morbidity, graft survival and even
      mortality. This review will discuss the current understanding of the
      epidemiology, diagnosis and therapy of adenovirus infection in transplant
      recipients. RECENT FINDINGS: Advances in the field include the use of polymerase
      chain reaction in the diagnosis of adenoviral infection, a better understanding
      of the epidemiology, immune response and potential new therapies, including
      preemptive and adoptive immunotherapy strategies. Adenoviral infections appear to
      be common, especially in pediatric solid organ transplant. Generally well
      tolerated, some high-risk patients may develop disseminated disease causing graft
      failure, which may lead to retransplant and/or death. Antiviral therapy and
      immunotherapy may play a role in these patients, although prospective controlled
      data are not available at this time. SUMMARY: Although new tools and a better
      understanding of the epidemiology, risk factors and therapies for adenovirus are
      beginning to materialize, prospective, controlled trials, using careful
      definitions, and standardized methodologies need to be performed to more fully
      clarify these issues in solid organ transplant recipients.

PMID- 19741533
TI  - Mycobacterium tuberculosis infection in transplant recipients: early diagnosis
      and treatment of resistant tuberculosis.
AB  - PURPOSE OF REVIEW: To provide a better understanding and summarize recent
      advances in the diagnosis and treatment of Mycobacterium tuberculosis (MTB)
      infection in solid organ transplant (SOT) candidates and recipients. RECENT
      FINDINGS: Despite advances in SOT medicine, MTB causes substantial morbidity and
      mortality in SOT recipients, with reported prevalence rates of 0.4-6%. The
      primary source of posttransplant MTB is reactivation of pretransplant latent MTB
      infection. The short-term mortality rate in SOT recipients with drug-susceptible
      active MTB is 30%. In immunocompromised persons with extensively drug-resistant
      MTB, the mortality rate approaches 100%. Clinical presentation is often atypical
      with more than half of SOT recipients presenting with extrapulmonary or
      disseminated disease. Pretransplant latent MTB infection screening and treatment
      is the cornerstone for preventing reactivation and dissemination of active MTB
      posttransplant. Treatment of active MTB in SOT recipients is problematic, given
      significant drug toxicity and interaction with immunosuppressive agents. SUMMARY:
      A high degree of suspicion for latent and active MTB infection in SOT candidates
      and recipients is warranted to establish a timely diagnosis and initiate life
      saving appropriate therapy.

PMID- 19741534
TI  - Utility of the virtual crossmatch in solid organ transplantation.
AB  - PURPOSE OF REVIEW: Solid-phase assays covered with single HLA molecules - such as
      single-antigen flow-beads (SAFBs) - allow determining the presence of donor
      specific HLA antibodies (HLA-DSAs) 'virtually' by comparison of the HLA-antibody
      specificities of the recipient with the HLA typing of the donor. In this review,
      prospects and current limitation of the virtual crossmatch are discussed. RECENT
      FINDINGS: Several prospective and retrospective studies indicate that a negative
      virtual crossmatch is associated with a very low risk of early rejection and good
      long-term allograft survival. By contrast, a positive virtual crossmatch is
      associated with a significant risk for early rejection and decreased allograft
      survival. However, these studies revealed that not all HLA-DSAs detected by SAFB
      have a detrimental clinical impact. SUMMARY: The virtual crossmatch has emerged
      as a very useful tool for pretransplant risk assessment and organ allocation.
      Further advances of the virtual crossmatch approach will require improvements on
      the technical part of SAFB analysis and a better understanding and definition of
      pathogenic factors of HLA-DSA. Together with an extended HLA typing of the donor,
      this scenario will provide us the full benefits of applications based on virtual
      crossmatching.

PMID- 19741535
TI  - Voice therapy and vocal nodules in adults.
AB  - PURPOSE OF REVIEW: This review considers recent and significant information
      pertinent to voice therapy for vocal nodules. RECENT FINDINGS: Available evidence
      suggests that voice therapy directed to excessive, hyperfunctional and
      maladaptive vocal practices can be effective in improving voice quality and
      reducing size/extent of pathology. However, there is also a growing literature
      suggesting that behavioral approaches may not be sufficient to permanently heal
      tissue changes in some patients, regardless of compliance with treatment aims,
      due to lasting structural damage in the vocal fold cover. This evidence
      underscores the need for early identification and education in individuals at
      risk for nodules. SUMMARY: The relationship between vocal nodules and excessive,
      phonotraumatic voice use is well established. Voice therapy typically consists of
      education regarding vocal fold mechanics and etiological factors, as well as
      modification of specific vocal practices that either cause, exacerbate or result
      from inappropriate voice production. Therapy can be effective in improving voice
      quality and tissue health but does not necessarily result in complete resolution
      of pathology. It should always be considered as a part of the treatment regimen
      for patients with vocal nodules.

PMID- 19741536
TI  - The role of potassium recirculation in cochlear amplification.
AB  - PURPOSE OF REVIEW: Normal cochlear function depends on maintaining the correct
      ionic environment for the sensory hair cells. Here we review recent literature on
      the cellular distribution of potassium transport-related molecules in the
      cochlea. RECENT FINDINGS: Transgenic animal models have identified novel
      molecules essential for normal hearing and support the idea that potassium is
      recycled in the cochlea. The findings indicate that extracellular potassium
      released by outer hair cells into the space of Nuel is taken up by supporting
      cells, that the gap junction system in the organ of Corti is involved in
      potassium handling in the cochlea, that the gap junction system in stria
      vascularis is essential for the generation of the endocochlear potential, and
      that computational models can assist in the interpretation of the systems biology
      of hearing and integrate the molecular, electrical, and mechanical networks of
      the cochlear partition. Such models suggest that outer hair cell electromotility
      can amplify over a much broader frequency range than expected from isolated cell
      studies. SUMMARY: These new findings clarify the role of endolymphatic potassium
      in normal cochlear function. They also help current understanding of the
      mechanisms of certain forms of hereditary hearing loss.

PMID- 19741537
TI  - Evolving techniques to evaluate ejaculatory function.
AB  - PURPOSE OF REVIEW: Recent findings in the physiology and neurobiology of
      ejaculation have expanded our understanding of male sexual function and have
      allowed the development of new instruments to investigate ejaculatory and
      orgasmic disorders. RECENT FINDINGS: The evidence-based definition of lifelong
      premature ejaculation has set a model in the evaluation and treatment outcome of
      sexual dysfunction. New instruments to objectively assess arousal, orgasm and the
      expulsion phase of ejaculation such as functional MRI, dynamic pelvic ultrasound,
      PET scans and validated questionnaires have lead to a better understanding of
      sexual dysfunction in men. Animal models, developments in neurobiology and
      clinical experience have transformed a purely psychoanalytical approach to
      ejaculatory and orgasmic function into a novel multidisciplinary, scientifically
      sound and evidence-based discipline of medicine. SUMMARY: Ejaculation is an
      integral part of normal sexual function. Ejaculatory dysfunction is common and
      may cause substantial disruption to the quality of a patient's life. A better
      understanding of the epidemiology, pathophysiology, neuroscience and genetics of
      ejaculatory and orgasmic function will eventually lead to the development of new,
      effective methods of treatment of disorders of ejaculation and orgasm in men.

PMID- 19741538
TI  - Surgical and minimally invasive treatments for Peyronie's disease.
AB  - PURPOSE OF REVIEW: Peyronie's disease is a relatively common condition affecting
      men with estimates of current prevalent rates ranging from 1 to 4%. However, it
      has no clear management protocols, primarily due to a lack of high quality
      evidence in support of treatment options. This article aims to review the recent
      published literature on management strategies for Peyronie's disease. RECENT
      FINDINGS: Intralesional interferon therapy has shown to result in significant
      improvement in Peyronie's disease plaques and curvature. Intralesional verapamil
      and extracorporeal shock wave therapy may help retard the progression of disease.
      Acellular, extracellular matrix-based grafts provide durable long-term
      satisfactory results in men requiring complex reconstruction. SUMMARY: Further
      clinical trails are warranted to evaluate the role of oral systemic therapies for
      early Peyronie's disease. Injection therapy, primarily with interferon, seems to
      be the most promising treatment for early stage Peyronie's disease. For men with
      established plaques, surgery using either plication or grafts forms the mainstay.
      There is an increasing trend to use autologous graft material that is
      commercially available and avoids donor site complications from autologous
      tissue.

PMID- 19741539
TI  - Gene transfer for erectile dysfunction: will this novel therapy be accepted by
      urologists?
AB  - PURPOSE OF REVIEW: The purpose of this review is to update the results of the
      only phase 1 erectile dysfunction gene transfer trial and based upon those
      results present the outcome of a web-based survey that studied whether or not
      knowledgeable in the field urologists would use gene transfer in their patients
      once approved for use by the US Food and Drug Administration. RECENT FINDINGS:
      The results of the clinical trials showed no transfer-related serious adverse
      events. The response to 10 questions of a web-based survey indicates that gene
      transfer as a first or second-line therapy for practicing urologists would be
      well accepted. SUMMARY: Practicing, experienced urologists, after the US Food and
      Drug Administration approval, are willing to employ gene transfer therapies in
      their patients, be it men who have failed or dissatisfied with other treatments
      or as shown in up to one-third of men as a first therapy. That outcome portends
      for rapid adaptation and active participation into the medical practice for maxi
      K or other specific gene transfer, stem cell, or combinations that will be
      developed in the future.

PMID- 19741540
TI  - Effect of a sequential training programme on inflammatory, prothrombotic and
      vascular remodelling biomarkers in hypertensive overweight patients with or
      without metabolic syndrome.
AB  - BACKGROUND: It is not known whether serum level of vascular remodelling
      parameters, such as matrix metalloproteinases could be modulated by physical
      activity and whether the eventual change could be influenced by metabolic
      syndrome (MS) diagnosis. DESIGN: Open, intervention study to evaluate the effects
      of a sequential physical activity training on inflammatory, prothrombotic and
      vascular remodelling biomarkers in overweight patients with and without MS.
      METHODS: We enrolled 80 overweight patients (mean age: 62.9+/-8.3 years; male :
      female = 36 : 44) with newly diagnosed hypertension, with or without MS. After 3
      months of American Heart Association step 2 diet, they followed a sequential
      training programme including 56 days of added three metabolic equivalent
      tasks/week and 56 days of six metabolic equivalent tasks/week. RESULTS: All
      patients experienced a significant decrease in body mass index, waist
      circumference and blood pressure after both the training phases. High-density
      lipoprotein-cholesterolemia, triglycerides, and glycaemia significantly improved
      only after the intensive training phase compared with the baseline in MS
      patients. Prothrombotic parameters improved irrespectively from the MS diagnosis.
      High-sensitivity C-reactive protein P level significantly decreased towards
      baseline and towards the previous phase, after exercise intensification, but only
      in MS patients. The plasma level of matrix metalloproteinase 2 and 9, and their
      activated forms improved significantly when compared with the baseline both after
      the first and the second training period, independently from the MS diagnosis.
      CONCLUSION: Diagnosis of MS is a determinant of changes in metabolic and
      inflammatory biomarkers, but not of the prothrombotic and vascular remodelling
      ones in a sample of overweight hypertensive patients.

PMID- 19741541
TI  - Lack of supervision after residential cardiac rehabilitation increases
      cardiovascular risk factors.
AB  - BACKGROUND: Cardiovascular rehabilitation (CR) is an important component of care
      for patients with cardiovascular disease (CVD) and has been well documented and
      promoted by various health organizations and position statements worldwide.
      PURPOSE: The purpose of this study was to investigate whether patients readmitted
      to CR on average 16 months after their previous discharge, maintained the
      reduction in CVD risk factors, maintained or improved functional capacity,
      occurrence of adverse cardiovascular events, and possible modifications in
      prescribed medications. METHODS: Five hundred and seventy patients (60+/-10
      years) underwent cycle ergometry and blood sampling at the beginning, the end of
      21+/-2 days of the previous CR, and again at readmission to CR. The CR consisted
      of cycling for 17+/-4 min at frequency of six times a week and daily walking for
      45 min at 60-70% of the maximal individual heart rate. RESULTS: Blood total
      cholesterol, low-density lipoprotein-cholesterol, triglycerides, and body mass
      index decreased significantly during CR. Resting blood pressure, maximal
      performance (watts), maximal oxygen uptake, and heart rate recovery improved
      significantly in 1 min (P<0.001). At readmission, all traditional CVD risk
      factors increased significantly, although medication was unchanged and
      angiotensin-converting enzyme inhibitors were partly replaced by angiotensin II
      receptor antagonists. Exercise performance remained unchanged. CONCLUSION: At
      readmission, we observed an increase in CVD risk factors, although, physical
      fitness remained stable. Thus, failure of lifestyle modification after CR
      indicates the cause for concern. Reinforcement of home setting sessions of CR
      patients or other strategies to enhance long-term compliance to lifestyle changes
      could reduce the observed attrition in CR benefits.

PMID- 19741542
TI  - Recalibration and validation of the SCORE risk chart in the Australian
      population: the AusSCORE chart.
AB  - BACKGROUND: Development of a validated risk prediction model for future
      cardiovascular disease (CVD) in Australians is a high priority for cardiovascular
      health strategies. DESIGN: Recalibration of the SCORE (Systematic COronary Risk
      Evaluation) risk chart based on Australian national mortality data and average
      major CVD risk factor levels. METHODS: Australian national mortality data (2003
      2005) were used to estimate 10-year cumulative CVD mortality rates for people
      aged 40-74 years. Average age-specific and sex-specific levels of systolic blood
      pressure, total cholesterol and prevalence of current smoking were generated from
      data obtained in eight Australian large-scale population-based surveys undertaken
      from the late 1980s. The SCORE risk chart was then recalibrated by applying
      hazard ratios for 10-year CVD mortality obtained in the SCORE project.
      Discrimination and calibration of the recalibrated model was evaluated and
      compared with that of the original SCORE and Framingham equations in the Blue
      Mountains Eye Study in Australia using Harrell's c and Hosmer-Lemeshow chi
      statistics, respectively. RESULTS: An Australian risk prediction chart for CVD
      mortality was derived. Among 1998 Blue Mountains Eye Study participants aged 49
      74 years with neither CVD nor diabetes at baseline, the Harrell's c statistics
      for the Australian risk prediction chart for CVD mortality were 0.76 (95%
      confidence interval: 0.69-0.84) and 0.71 (confidence interval: 0.62-0.80) in men
      and women, respectively. The corresponding Hosmer-Lemeshow chi statistics, the
      measure of calibration, were 2.32 (P = 0.68) and 7.43 (P = 0.11), which were
      superior to both the SCORE and Framingham equations. CONCLUSION: This new tool
      provides a valid and reliable method to predict risk of CVD mortality in the
      general Australian population.

PMID- 19741543
TI  - Reasonable design of antibody mimetics for targeting glioma and small cell lung
      cancer.
AB  - According to the recent research available from the American Cancer Society,
      cancer is the second leading cause of death in the USA. Many kinds of
      chemotherapeutic agents have been shown to be effective against tumor cells.
      Unfortunately, most of them also kill normal cells. Because native antibodies and
      antibody fragments find it hard to penetrate solid tumors, most approaches have
      focused on developing antibody mimetics. Therefore, we wanted to design more
      reasonable antibody mimetics, containing three regions, for targeting glioma and
      small cell lung cancer, and supposed that these mimetic-toxin immunotoxins could
      specifically kill targeting tumors. VLCDR1 and VHCDR3, together with five amino
      acid residues on both sides of the complementarity-determining regions, through a
      cognate framework region (VHFR2) yielded mimetics of BT32/A6 (United States
      Patent number: 5639863) and TB2A36C3 (United States Patent number: 5744585). When
      genetically fused, the mimetic with the first 388 amino acid residues of
      diphtheria toxin, Escherichia coli strain, BL21 (ED3), was used for expression of
      soluble immunotoxins DT-BT and DT-TB. The killing activities of our fusion
      proteins were examined in vitro. DT-BT and DT-TB could not kill Raji up to the
      maximal concentration tested (10-7 mol/l) in vitro. In contrast, at
      concentrations >= 10-8 mol/l, DT-BT and DT-TB killed 90% of U-87 MG cells and
      small cell lung cancer in vitro, respectively. The killing activities of our
      fusion proteins hinted that 5aa-VLCDR1-5aa-VHFR2-5aa-VHCDR3-5aa mimetics
      maintained the synergic interactions and high affinity of parent antibodies. Such
      mimetics may hold promise for markedly improving cancer diagnostics and
      therapeutics, especially as the small size of the mimetics may confer other
      useful properties, such as enhanced intracellular delivery.

PMID- 19741544
TI  - Prognostic significance of fascin-1 and E-cadherin expression in laryngeal
      squamous cell carcinoma.
AB  - Fascin-1 and E-cadherin, both of which are related to cell motility and cell
      adhesiveness, are important factors in the progression and metastasis of cancers.
      The objective of this study was to explore the association between fascin-1 and E
      cadherin expression levels with both the clinical characteristics and prognoses
      of patients with laryngeal squamous cell carcinoma; we did so through statistical
      analyses. In our study, tumor tissue samples from 150 patients with laryngeal
      squamous cell carcinoma were examined for fascin-1 and E-cadherin expression by
      immunohistochemistry. Fascin-1 expression was found to be an independent
      predictive factor for recurrence in patients with laryngeal squamous cell
      carcinoma (P = 0.021) and independently related to disease-free survival (P =
      0.010). Although E-cadherin expression status was not an independent predictive
      factor for recurrence (P = 0.055) or disease-free survival (P = 0.063), when
      using subgroup analysis, the subgroup with high fascin-1 expression/low E
      cadherin expression had the poorest prognosis (P = 0.000). Fascin-1 expression
      could be a potential prognostic predictor for patients with laryngeal squamous
      cell carcinoma. Simultaneous analyses of fascin-1 and E-cadherin expression could
      be more effective in evaluating the prognoses of patients with laryngeal squamous
      cell carcinoma.

PMID- 19741545
TI  - Prevalence and distribution of high-risk human papillomavirus in Greece.
AB  - As knowledge of regional human papillomavirus (HPV) type distribution is
      essential for the optimization of prevention strategies, this study was carried
      out to explore the prevalence and type distribution of high-risk HPV in a
      screening population across Greece. Cervical samples were collected by local
      physicians and nurses in hospitals and health centers across the country from
      4139 women attending for cervical cancer screening. High-risk HPV-DNA was
      detected by using Hybrid Capture-2 (HC2) and positive samples with adequate
      cellular content were further typed by restriction fragment length polymorphism
      polymerase chain reaction. Almost six percent (5.9%) of women tested positive in
      HC2. The most common type was HPV16 (1.4% in the whole sample and 32.4% of the
      typed samples), followed by HPV53 (0.6 and 14.0%, respectively), HPV31 (0.6 and
      12.9%, respectively), HPV35 (0.5 and 12.3%, respectively), HPV51 (0.4 and 7.8%,
      respectively), HPV18 (0.3 and 7.3%, respectively) and 22 more types. Almost 15%
      of the typed samples showed a coinfection with two HPV types and 2.1% with three
      types. There was a bimodal distribution by age, with the highest peak in women 20
      29 years old and a lower peak in women 50-59 years old. Apart from the types
      originally included in HC2 cocktail, PCR analysis identified 15 more types (HPV6,
      HPV11, HPV34, HPV37, HPV38, HPV42, HPV53, HPV54, HPV55, HPV61, HPV62, HPV66,
      HPV73, HPV82, HPV83). Eleven percent of HC2-positive results arose from single
      type infections with HPV53 (10%) and HPV66 (1%), which are potentially high-risk
      types. In conclusion, HPV16 is the most common type in the largest Greek
      screening sample used to date and, together with its related types, accounts for
      more than half of high-risk HPV infections. Approximately 10% of positive HC2
      results arise from HPV53, which is not normally detected by the test, but may be
      clinically significant.

PMID- 19741546
TI  - Eosinophilic gastritis with idiopathic thrombocytopaenic purpura: coincidence or
      association?
AB  - A 70-year-old woman with a 3-year history of a nonhealing benign gastric ulcer
      developed spontaneous bruising and mouth ulceration. After haematological
      investigations, a diagnosis of idiopathic thrombocytopaenic purpura was made. At
      this stage, repeat biopsies of the gastric ulcer revealed features of
      eosinophilic gastritis. This is the first report of simultaneous diagnosis of
      idiopathic thrombocytopaenic purpura and eosinophilic gastritis. Both conditions
      are considered to be autoimmune induced and could be causally related. Oral
      steroid therapy led to a full recovery from both conditions.

PMID- 19741547
TI  - Improved employment rates after multiprofessional cross-sector cooperation in
      vocational rehabilitation: a 6-year follow-up with comparison groups.
AB  - The objective of this study was to better understand the long-term effects of an
      improved model for cooperation on employment between rehabilitation professionals
      in vocational rehabilitation (VR). To compare these effects with those associated
      with the traditional model of cooperation. The study featured a group of patients
      who participated in a developmental project. All of the patients had some degree
      of restricted work capacity, which was evidenced somatically as well as
      mentally/socially. They had all experienced long periods of unemployment during
      the 2-year period before the intervention. A 'natural experiment study design'
      that relied on database records was used. Using matching criteria, we identified
      'social twins' from a government register to create comparison groups at the
      local, county and national levels (n = 4 x 51 patients). Repeated-measures
      analysis of variance and logistic regression were used to analyse the data. The
      majority (59%) of the study group was employed 3 years after the intervention
      compared with 39 and 41% in the two matched control groups, respectively. The
      corresponding figures after 6 years were 51 versus 39 and 37%. An individual with
      a somatically restricted work capacity was about twice as likely to secure
      gainful employment following VR as compared with an individual with a
      mentally/socially restricted work capacity. In conclusion, the study focused on
      an improved method of cooperation between rehabilitation actors in the context of
      VR programmes. A model that included systematic multiprofessional cross-sector
      group meetings was explored, and we concluded that a substantial percentage of
      the enrolled patients successfully secured employment over a 6-year period. This
      percentage exceeded that of matched pairs in a county and national group; we
      presume that these groups represented 'the usual form of cooperation'.

PMID- 19741548
TI  - Ascending aorta impending rupture: successful surgical management in a patient
      with type IV Ehlers-Danlos syndrome.
AB  - Ehlers-Danlos syndrome is an inherited disorder of the connective tissue
      characterized by increased elasticity of the skin, hypermobile joints and
      fragility of the vascular system. Vascular complications in these patients,
      requiring surgical repair, can be life-threatening with high perioperative
      morbidity and mortality. Reports of successful treatment of aortic ruptures or
      dissections in vascular Ehlers-Danlos syndrome patients are rare. We describe our
      surgical technique and precautions in an Ehlers-Danlos syndrome patient with a
      contained rupture of the ascending aorta, requiring emergency surgical
      intervention.

PMID- 19741549
TI  - Left ventricular torsion in paced patients.
AB  - BACKGROUND: In healthy people the left ventricle presents a counter-clockwise
      apical rotation and a clockwise basal rotation ending in late systole. In early
      systole (during isovolumic contraction) there is a fast and inverse rotation
      (counter-clockwise at the base and clockwise at the apex). This opposite rotation
      between apex and base produces the systolic torsion of the left ventricle. The
      effect of permanent conventional pacing on this torsion is little known.
      OBJECTIVES: The aim of this study was to assess, by speckle tracking
      echocardiography, left ventricular rotation and torsion in patients
      conventionally paced at the apex of the right ventricle. METHODS: Left
      ventricular apical and basal rotation and the consequent torsion were evaluated
      by means of speckle tracking echocardiography, in 13 paced patients, without
      ischemic or valvular disease, and in 17 healthy participants. Left ventricular
      dyssynchrony was evaluated by means of temporal uniformity of strain. RESULTS: In
      the paced group there was a significant reduction in early-systolic clockwise
      torsion (-0.4 degrees +/- 1.2 vs. -1.5 degrees +/- 1.6; P = 0.04), and in late
      systolic counter-clockwise torsion (15.1 degrees +/- 4.3 vs. 19.1 degrees +/-
      5.5; P = 0.03). Circumferential temporal uniformity of strain averaged
      significantly lower in paced patients. CONCLUSIONS: Conventional pacing from the
      apex of the right ventricle alters both the torsional mechanic and the synchrony
      of the left ventricle.

PMID- 19741550
TI  - Limb sparing reconstructive surgery and Ilizarov lengthening in fibular hemimelia
      of Achterman-Kalamchi type II patients.
AB  - The aim of this study is to evaluate the long-term results of management of
      fibular hemimelia (Achterman-Kalamchi type-II) using the Ilizarov method. We
      reviewed 157 consecutive patients (180 limb segments) with a mean follow-up
      period of 10.7 years (1.2-21 years). The results were favorable. Although, this
      type of management is technically demanding and entails a lengthy procedure with
      many complications anticipated, the Ilizarov lengthening after limb
      reconstruction is still an option for management of this type of limb deficiency.

PMID- 19741551
TI  - Anteromedial plantar nodules of the heel in childhood: a variant of the
      normality?
AB  - Localized, bilateral, painless, nonpruritic and symmetric papuloid lesions in the
      posteromedial part of the foot are the clinical features of benign plantar
      nodules of the heel in children. They are probably congenital; they are
      asymptomatic and benign. We present 18 children with posteromedial nodules of the
      heel, 15 bilateral. Mean age was 45.31+/-53.49 months. The reason for the
      consultation was the lump itself in 10 of the cases. Thirteen were asymptomatic
      and five presented transient tenderness to pressure. Radiographs were nonspecific
      in all cases. Sonography showed an accumulation of tissue similar to subcutaneous
      cell tissue, compatible with fat. MRI was performed in one case, showing an
      accumulation of fatty tissue similar to subcutaneous cell tissue. Follow-up time
      was 5.44+/-3.78 years (range 2-16 years). At the end of follow-up, all the
      patients are asymptomatic with normal functional outcome and with the lump
      persisting in all but one. In conclusion, a sonographic study is sufficient to
      diagnose this type of mass, without the need for biopsy and/or surgical exeresis
      to distinguish fatty tissue from another type of consistency. Subsequent studies
      should aim at showing piezogenic, hamartomatous or congenital fat herniation
      aetiology of these typical lumps, probably normal variant of normality.

PMID- 19741552
TI  - Acidic catalase in human skin in vivo: a new marker of permanent damage.
AB  - Malignant melanoma incidence is increasing rapidly in Western countries. Its
      prevention requires a deep knowledge of the biological basis of the neoplasm
      leading to the identification of new biological risk markers. In in-vitro and ex
      vivo models we demonstrated that catalase was modified not only in its activity
      but also in its charge properties after ultraviolet A irradiation through
      pheomelanin. Here we focus on the electrophoretic behaviour of catalase in the
      human skin in vivo, in association with cutaneous phototype. Zymographic analysis
      of the enzyme on skin biopsies from Caucasian population (phototype I-IV),
      collected from the trunk in autumn-winter, to exclude possible influences of an
      acute photoexposure, evidenced a protein doublet, representing the coexistence of
      two active isoforms of catalase with different charge properties. In the skin
      from low-phototype subjects, the percent contribution of the more acidic
      component of the doublet was prevalent, inversely correlated with total melanin
      concentration in hair, and associated with a high number of melanocytic nevi. In
      summary, this study shows for the first time the existence of an acidic catalase
      in association with clinically defined risk characteristics in low phototype skin
      in vivo, contributing to the knowledge of a new biochemical marker of cutaneous
      photosusceptibility.

PMID- 19741553
TI  - Characterization of an animal model of postmenopausal cardiac hypertrophy and
      novel mechanisms responsible for cardiac decompensation using ovariectomized
      pressure-overloaded rats.
AB  - OBJECTIVE: The development of animal models of cardiovascular disease are
      critical to define pathophysiological mechanisms and to advance diagnosis and
      therapy. The lack of a suitable animal model represents a failure to define the
      mechanisms responsible for postmenopausal myocardial hypertrophy in hypertension
      and adverse cardiac remodeling. METHODS: In this review, we presented a rat model
      of postmenopausal myocardial hypertrophy, with particular focus on the
      similarities between the animal model and postmenopausal women regarding
      myocardial function as well as molecular and subcellular mechanisms. To elucidate
      the molecular mechanism of left ventricular (LV) hypertrophy and remodeling in
      postmenopausal women, we analyzed myocardial hypertrophy as well as cardiac
      function and hypertrophy-related protein expression in ovariectomized (OVX) and
      pressure overloaded (PO) rats. RESULTS: The model is characterized by depletion
      of serum estrogen and increased heart-to-body weight and lung-to-body weight
      ratios. Moreover, the OVX-PO rats also show increased mean arterial blood
      pressure, LV end-diastolic pressure, LV developed pressure, and maximal rates of
      LV contraction and relaxation compared with the OVX group. Importantly, Akt
      activity was largely attenuated, and both endothelial nitric oxide synthase
      expression and activity were markedly reduced in the OVX-PO group. Finally,
      significant increased mortality was observed in the OVX-PO group after chronic
      isoproterenol administration. CONCLUSIONS: Our results demonstrate that rats
      subject to OVX are unable to compensate for hypertrophy partly due to impaired
      Akt-endothelial nitric oxide synthase signaling along with deteriorated heart
      function and demonstrated increased mortality. In this review, we discussed the
      mechanisms of cardiac injury, which could play a critical role in postmenopausal
      hypertrophy, as well as the characteristics of the OVX-PO female rats as a model
      to test cardioprotective drugs in postmenopausal women.

PMID- 19741555
TI  - Donald R. Korb, OD, FAAO: Clinician Scientist, Colleague, and Teacher.
AB  - Discovery often begins with a clinical observation that leads to major biomedical
      discovery. Therefore, well-trained clinical scientists are an important part of
      the discovery process. Unfortunately, both medicine and optometry have too few
      well-trained clinician scientists. However, among the few, Dr. Donald Korb stands
      out as the quintessential optometric clinical scientist. This profile provides
      insights into the life, thoughts, and unusually productive professional career of
      Dr. Korb. Of particular interest for many contact lens clinicians is a discussion
      with Dr. Korb on how some of his clinical observations led to improved diagnostic
      and treatment procedures.

PMID- 19741556
TI  - Contact lens-related acanthamoeba keratitis.
AB  - Acanthamoeba keratitis is a rare but severe disease, with more than 95% of cases
      occurring in contact lens wearers. With a worldwide resurgence of contact lens
      related disease, this report illustrates the clinical characteristics and
      treatment challenges representative of this disease. This report describes
      Acanthamoeba keratitis in a 47-year-old female using extended wear silicone
      hydrogel contact lenses, with a history of swimming in a home pool and failure to
      subsequently disinfect the contact lenses. The diagnosis was based on clinical
      signs, disease course, and confocal microscopy results despite a negative result
      for corneal smear and culture. The corneal signs included an epithelial defect,
      epithelial irregularities, anterior stromal infiltrates, perineural infiltrates,
      an anterior stromal ring infiltrate, and hypopyon. The case was diagnosed as an
      infective keratitis and treated promptly using intensive topical administration
      of fortified gentamicin and cephalothin. The high likelihood Acanthamoeba
      prompted immediate use of polyhexamethylbiguanide and chlorhexidine, with
      propamide and adjunct treatment using atropine and oral diclofenac. Steroids were
      added on day 3, and the frequency of administration of antibacterial treatment
      was gradually reduced and ceased by day 10. The analgesia was stopped at 3
      months. The frequency of administration of antiamoeba therapy and steroid
      treatment was slowly reduced and all treatment was ceased after 18 months.
      Despite considerable morbidity in terms of the treatment duration,
      hospitalization, outpatient appointments, and associated disease costs, the final
      visual outcome (6/6) was excellent.

PMID- 19741557
TI  - Management of symptomatic Meesmann dystrophy.
AB  - Meesmann dystrophy is a non-progressive autosomal dominant corneal epithelial
      dystrophy characterized by intraepithelial cysts, which is likely to be caused by
      an intraepithelial metabolic abnormality. Cases may be asymptomatic or be
      associated with symptoms of irritation, lacrimation, and photophobia. Palliative
      treatment includes ocular lubricants, cycloplegia, and therapeutic contact
      lenses. In severe cases, management with epithelial debridement, phototherapeutic
      keratectomy, and lamellar keratoplasty has been advocated. Most recently, the
      genetic and molecular basis of Meesmann dystrophy have been explored, and
      mutations in the genes encoding corneal epithelial keratins have been reported.
      This report describes a case of Meesmann dystrophy with unusually severe symptoms
      and punctate epithelial keratopathy managed with a therapeutic contact lens.

PMID- 19741559
TI  - Treatment of primary pterygium.
AB  - PURPOSE: To compare preserved human amniotic membrane transplantation and
      conjunctival autografts for treatment of primary pterygium. METHODS: Thirty-seven
      eyes of 35 patients with primary pterygium underwent surgical excision. In group
      A, 25 eyes were treated with conjunctival autografts. In group B, 12 eyes were
      treated with preserved human amniotic membrane transplantation. These two groups
      were compared in terms of complications, recurrence, and final appearance,
      prospectively. RESULTS: We observed two cases of recurrence in group A and five
      cases of recurrence in group B. The onset of recurrence was about 5.5 months in
      both groups. We observed two eyes with Dellen ulcer and one case with a Tenon's
      cyst in the superior temporal quadrant in group A and one case of Dellen ulcer
      and granulation tissue of one eye in group B. CONCLUSIONS: We suggest that free
      conjunctival autografting is a more effective technique in primary pterygium in
      terms of lowering recurrences compared with the amniotic membrane transplantation
      technique.

PMID- 19741560
TI  - Corneal and refractive astigmatism in adults: a power vectors analysis.
AB  - PURPOSE: In this article, we examine the relationship between corneal and
      refractive astigmatism (including with the rule, against-the-rule, and oblique
      astigmatism) in an adult population using power vectors. METHODS: Refractive and
      keratometric measures of astigmatism were conducted on right eyes of 105 white
      subjects aged 18 to 59 years. We performed a linear regression of refractive
      astigmatic error on corneal astigmatism, using the J0 and J45 components of the
      astigmatism. RESULTS: We obtained a statistically significant regression
      relationship between the corneal (C) and refractive (R) astigmatism for both J0
      and J45 components, namely, RJ0 = 1.07 * CJ0 - 0.28; and RJ45 = 1.46 * CJ45 +
      0.03. This results is a kind of generalized Javal rule for an adult population,
      because it is extended to include oblique astigmatism. We also found that the
      internal astigmatism is against-the-rule and uniform in our sample. CONCLUSIONS:
      This vector-based approach is equivalent to the traditional Javal rule, but it
      has the ability to make predictions about oblique astigmatism, rendering it more
      general and more accurate.

PMID- 19741561
TI  - Tear meniscus height determination using the OCT2 and the RTVue-100.
AB  - PURPOSE: To compare anterior segment spectral-domain optical coherence tomography
      (SOCT) tear meniscus height (TMH) measures with those from the more commonly used
      time-domain OCT (TOCT). METHODS: The right eye of 50 healthy subjects had images
      of their TMH captured with TOCT (OCT2) and SOCT (RTVue-100). Data were acquired
      using two different anterior segment lenses, the cornea/anterior module-short
      (CAM-S) and long (CAM-L), on the SOCT. Images were then analyzed for differences
      in their derived TMH. RESULTS: The average TMH for TOCT was 0.280 +/- 0.139 mm,
      whereas the mean TMH measured using the SOCT was 0.354 +/- 0.163 mm and 0.345 +/-
      0.167 mm for the CAM-S and CAM-L, respectively. There was a significant
      difference (p < 0.001) when comparing TOCT with either of the SOCT lenses. There
      was no statistically significant difference between the CAM-L and CAM-S (p =
      1.0). Bland-Altman analysis showed poor agreement between TOCT and SOCT (95%
      limits of agreement -0.138 to + 0.285 mm for the CAM-S and -0.185 to +0.315 mm
      for the CAM-L). CONCLUSIONS: The RTVue-100 produces TMH measurements that are
      significantly higher than OCT2 in a normal patient population. However, the RTVue
      100 showed a number of other advantages over the OCT2 in the measurement and
      analysis of images. Future work needs to determine the causative factors behind
      the observed differences.

PMID- 19741558
TI  - Academic behaviors in children with convergence insufficiency with and without
      parent-reported ADHD.
AB  - PURPOSE: To determine if children with symptomatic Convergence Insufficiency
      without the presence of parent-reported Attention Deficit Hyperactivity Disorder
      (ADHD) have higher scores on the academic behavior survey (ABS). METHODS: The ABS
      is a 6-item survey that evaluates parent concern about school performance and the
      parents' perceptions of the frequency of problem behaviors that their child may
      exhibit when reading or performing schoolwork (such as difficulty completing
      work, avoidance, and inattention). Each item is scored on an ordinal scale from 0
      (Never) to 4 (Always) with a total score ranging from 0 to 24. The survey was
      administered to the parents of 212 children 9- to 17-year old (mean age 11.8
      years.) with symptomatic convergence insufficiency before enrolling into the
      Convergence Insufficiency Treatment Trial and to 49 children with normal
      binocular vision (NBV) (mean age 12.5 years). The parents reported whether the
      child had ADHD, and this information was used to divide the symptomatic
      convergence insufficiency group into the convergence insufficiency with parent
      report of ADHD or convergence insufficiency with parent report of no ADHD groups.
      RESULTS: Sixteen percent of the convergence insufficiency group and 6% of the NBV
      group were classified as ADHD by parental report. An analysis of covariance
      showed that the total ABS score for the symptomatic convergence insufficiency
      with parent report of ADHD group (15.6) was significantly higher than the
      symptomatic convergence insufficiency with parent report of no ADHD group (11.7,
      p = 0.001) and the NBV group (8.7, p < 0.0001). Children with convergence
      insufficiency with parent report of no ADHD scored significantly higher on the
      ABS than the NBV group (p = 0.036). CONCLUSIONS: Children with symptomatic
      convergence insufficiency with parent report of no ADHD scored higher on the ABS,
      when compared to children with NBV. Children with parent report of ADHD or
      related learning problems may benefit from comprehensive vision evaluation to
      assess for the presence of convergence insufficiency.

PMID- 19741562
TI  - Rasch analysis of visual function and quality of life questionnaires.
AB  - PURPOSE: To investigate the psychometric properties of the Visual Function (VF)
      and Quality of Life (QOL) questionnaires, using the Rasch measurement model.
      METHODS: Four hundred eighty-nine patients with cataract awaiting surgery, drawn
      from the surgical waiting list of the Flinders Medical Centre, Adelaide, South
      Australia, were mailed the VF and QOL questionnaires for self-administration.
      Rasch analysis was undertaken to assess the following properties: measurement of
      a single construct (i.e., unidimensionality by fit statistics and principal
      components analysis), discrimination between strata of participant ability
      (person separation, recommended minimum value 2.0), targeting of item difficulty
      to participant ability, and differential item functioning (DIF, whether items
      function similarly for different subgroups and notable DIF defined as >1.0
      logit). RESULTS: The VF questionnaire fit the Rasch model showing good metric
      properties, including unidimensionality, and was free of notable DIF. The QOL
      questionnaire showed inadequate person separation, two misfitting items and
      significant multidimensionality (Eigenvalue of 2.3 for the first contrast),
      suggesting the presence of a separate subscale, self-care, but this was not valid
      because of inadequate person separation. Deleting these contrasting items from
      the QOL questionnaire removed multidimensionality and item misfit but did not
      improve person separation, indicating that it could not effectively discriminate
      between the participant's QOL. Both VF and QOL questionnaires demonstrated poor
      targeting (-2.22 and -3.26 logits, respectively), indicating that items were too
      easy and participants had higher QOL than that the items allowed for. Three items
      in the QOL questionnaire demonstrated notable DIF by age and systemic
      comorbidity. None of the subscales functioned optimally. CONCLUSIONS: The QOL
      questionnaire is not a valid measure of QOL. However, the VF questionnaire is a
      reliable and valid measure of visual disability in patients with cataract, and
      although targeting was suboptimal in a developed country, it may be optimal in a
      developing country as was originally intended.

PMID- 19741563
TI  - Myopia progression during three years of soft contact lens wear.
AB  - PURPOSE: To analyze the effect of lens material alone on myopia progression in a
      multi-center non-randomized prospective study of daily wear hydrogel and
      continuous wear silicone hydrogel contact lenses. METHODS: Refractive error data
      from completing subjects were collected during a 3-year study of 54 subjects
      wearing low-Dk/t hydrogel contact lenses for daily wear and 230 wearing silicone
      hydrogel contact lenses for up to 30 nights continuous wear. Univariate analysis
      of refractive error changes was first conducted on factors of lens type, age at
      baseline, and baseline refractive error. Multivariate analysis was then performed
      to control for potential confounders of age (categorical by decade and
      continuous), and baseline refractive error. RESULTS: Multivariate analysis showed
      that refractive error changes were significantly affected by lens type (F = 78.2,
      p < 0.001, R = 0.218) and subject age (F = 131.2, p < 0.001, R = 0.319) but not
      baseline refractive error (F = 2.56, p = 0.11, R = 0.009). The model's overall R
      value is 0.376; the age-adjusted refractive error changes are +0.02 D for the
      silicone hydrogel contact lens wearers and -0.41 D for the hydrogel contact
      lenses for the 3-year follow-up period. CONCLUSIONS: Subject age and lens type
      significantly influenced the degree of myopic progression, with younger subjects
      and low-Dk/t hydrogel contact lens wearers increasing more during the study. The
      Lotrafilcon A silicone hydrogel lens material may contribute to less myopia
      progression in adult contact lens wearers.

PMID- 19741564
TI  - Effect of DNA repair host factors on temozolomide or dacarbazine melanoma
      treatment in Caucasians.
AB  - OBJECTIVES: The efficacy of temozolomide (TMZ) or dacarbazine (DTIC) in melanoma
      treatment depends on low O-6-methylguanine-DNA-methyltransferase (MGMT) repair
      and on high mismatch repair. The aim of this study was to identify individual
      host markers for hematologic side effects and the treatment efficacy of TMZ or
      DTIC in melanoma treatment. METHODS: Fifty-one Caucasian patients with
      metastasized melanoma were recruited. In each patient, the mRNA expression of
      MGMT and two essential mismatch repair genes, MLH1 and MSH2, was measured in
      peripheral blood. The coding gene regions, including splice sites, were sequenced
      to identify genetic variants, and the promoter methylation status of the genes
      was determined. RESULTS: Both constitutively low and high mRNA expression of
      MGMT, MLH1, and MSH2 were significantly associated with reduced hematologic side
      effects (P = 0.008-0.020), but did not correlate with treatment efficacy. We
      identified five variants in the MGMT gene, 13 variants in MLH1, and seven
      variants in MSH2, including five novel genetic variants in MLH1. Variations of
      the hosts' gene expression of MGMT, MLH1, and MSH2 did not result from promoter
      methylation. Of note, one variant in MSH2 (rs2303428) was associated with
      increased hematologic side effects and showed a tendency for better treatment
      response. CONCLUSION: Our results indicate that either low or high host
      expression of MGMT, MLH1, and MSH2 may serve as a marker for reduced hematologic
      side effects of TMZ or DTIC, but not for treatment efficacy in melanoma. The
      genetic variant rs2303428 (MSH2) might serve as a predictive marker for
      hematologic side effects and treatment response.

PMID- 19741565
TI  - Effects of CYP4F2 genetic polymorphisms and haplotypes on clinical outcomes in
      patients initiated on warfarin therapy.
AB  - BACKGROUND: A variant in the CYP4F2 gene, rs2108622, has been recently shown to
      determine stable warfarin dose requirements. CYP4F2 has also been shown recently
      to metabolize vitamin K. METHODS: Three hundred and eleven patients were
      recruited prospectively from two UK hospitals and followed-up for 6 months. Fine
      mapping of the whole CYP4F2 region was performed to try and define the haplotype
      structure of CYP4F2. Genotyping was performed on the Sequenom platform.
      Univariate and multiple regression analyses were undertaken to assess the effect
      of CYP4F2 on predefined clinical outcomes of warfarin response. RESULTS: Fifty
      nine single nucleotide polymorphisms in the CYP4F2 gene were analyzed. There was
      a high degree of linkage disequilibrium in the gene with two haplotype blocks. No
      association was found with warfarin stable dose and rs2108622 in our prospective
      cohort of patients even after adjustments to reduce patient heterogeneity.
      Interestingly, a single nucleotide polymorphism (rs2189784), which is in strong
      linkage disequilibrium with rs2108622, showed an association with time-to
      therapeutic international normalized ratio which remained significant after the
      correction for multiple testing (Pc = 0.03). No association was shown with the
      haplotypes after false discovery rate correction. CONCLUSION: Although we were
      unable to demonstrate an association between rs2108622 and stable warfarin dose,
      our finding of an association between rs2189784 and time-to-therapeutic
      international normalized ratio is consistent with the recent finding that CYP4F2
      plays a role in vitamin K metabolism. However, the effect of CYP4F2 is relatively
      small in all studies undertaken so far, and thus seems unlikely to be of clinical
      relevance.

PMID- 19741566
TI  - CYP2D6: novel genomic structures and alleles.
AB  - OBJECTIVE: CYP2D6 is a polymorphic gene. It has been observed to be deleted, to
      be duplicated and to undergo recombination events involving the CYP2D7 pseudogene
      and surrounding sequences. The objective of this study was to discover the
      genomic structure of CYP2D6 recombinants that interfere with clinical genotyping
      platforms that are available today. METHODS: Clinical samples containing rare
      homozygous CYP2D6 alleles, ambiguous readouts, and those with duplication signals
      and two different alleles were analyzed by long-range PCR amplification of
      individual genes, PCR fragment analysis, allele-specific primer extension assay,
      and DNA sequencing to characterize alleles and genomic structure. RESULTS: Novel
      alleles, genomic structures, and the DNA sequence of these structures are
      described. Interestingly, in 49 of 50 DNA samples that had CYP2D6 gene
      duplications or multiplications where two alleles were detected, the chromosome
      containing the duplication or multiplication had identical tandem alleles.
      CONCLUSION: Several new CYP2D6 alleles and genomic structures are described which
      will be useful for CYP2D6 genotyping. The findings suggest that the recombination
      events responsible for CYP2D6 duplications and multiplications are because of
      mechanisms other than interchromosomal crossover during meiosis.

PMID- 19741567
TI  - Selective serotonin reuptake inhibitors pathway.

PMID- 19741568
TI  - Functional variants of the serotonin receptor type 3A and B gene are associated
      with eating disorders.
AB  - OBJECTIVE: As a key player in modulating both human physiological and behavioural
      functions including anxiety, perception and in particular appetite, serotonin (5
      hydroxytryptamine, 5-HT) is likely to be involved in the aetiology of eating
      disorders. Studies showing serotonin receptor type 3 (5-HT3) receptors to mediate
      food intake depression (anorexic response) have triggered our interest in
      investigating the putative role of variants in the 5-HT3 receptor genes, HTR3A
      and HTR3B, in the susceptibility to anorexia nervosa (AN) and bulimia nervosa
      (BN). METHODS: Two hundred and sixty-five patients with AN and 91 patients with
      BN as well as 191 healthy controls served as a pilot study group for mutational
      analysis by direct sequencing. Variants showing a significant association were
      subsequently genotyped in an independent Spanish cohort of 78 patients with AN
      and 119 patients with BN as well as 331 healthy controls for replication
      purposes. RESULTS: In the pilot study, we found the coding HTR3B variant,
      p.Y129S, (rs1176744, P = 0.004, odds ratio = 2.06) to be associated with the
      restrictive subtype of AN. The association was confirmed in the Spanish study
      group (P = 0.034, odds ratio = 2.26). CONCLUSION: Our study provides first
      evidence for an involvement of 5-HT3 variants in the aetiopathology of eating
      disorders in humans.

PMID- 19741569
TI  - Functional glutathione S-transferase genotypes among testicular germ cell tumor
      survivors: associations with primary and post-chemotherapy tumor histology.
AB  - PURPOSE: The pathogenesis of testicular germ cell tumor (TGCT) remains unknown.
      The aim of this study was to evaluate the pathogenic role of functional
      polymorphisms in detoxification enzymes among TGCT patients, through association
      studies of constitutive genotypes and medical parameters before and after
      chemotherapy. EXPERIMENTAL DESIGN: Germline deletion polymorphisms in the
      glutathione S-transferase mu 1 (GSTM1) and the GST theta 1 (GSTT1), and a
      functional single nucleotide polymorphism in GST pi 1 (GSTP1, Ile105Val), were
      analyzed in TGCT survivors (TCSs) (n = 675) and controls (n = 189). Statistical
      analyses were performed for the genotype distributions between the TCSs and
      control populations, and between the genotypes and clinicopathological parameters
      of the TCSs. RESULTS: The GST genotypes showed comparable distributions among the
      TCSs and the control population. However, the genotype combination
      GSTT1positive/GSTP1-GG or GSTP1-AG/GSTM1positive was more frequent among the TCSs
      [P = 0.050, odds ratio (OR): 1.47, 95% confidence interval (CI): 0.998-2.165].
      The combined genotype GSTT1positive/GSTP1AA/GSTM1positive was associated with
      decreased risk of development of pure embryonal carcinoma (P = 0.009, OR: 0.309,
      95% CI: 0.122-0.784) and the GSTP1-A-allele (i.e. genotypes GSTP-AA or GSTP-AG)
      was also associated with decreased risk for development of pure teratoma (P =
      0.032, OR: 0.326, 95% CI: 0.122-0.873). Furthermore, the GSTP1-A-allele was
      overrepresented within the 'good prognosis group' (P = 0.032, OR: 2.407, 95% CI:
      1.060-5.469), whereas the GSTM1nulltype was associated with the extent of TC
      qualifying as 'poor prognosis group' (P = 0.025, OR: 2.839, 95% CI: 1.104-7.301).
      The GSTP1-AG genotype was associated with necrosis in the tumor's post
      chemotherapy histology (P = 0.001, OR: 16.087, 95% CI: 1.930-134.087). Failure,
      after platinum-based chemotherapy, was associated with the GSTT1positive/GSTP-AA
      or GSTP-GG/GSTM1-positive genotype (P = 0.019, OR: 2.168, 95% CI: 1.130-4.160).
      CONCLUSION: This study confirms an association between the GSTP1-G-allele and
      TGCT. Combinations of GST genotypes were associated with primary and post
      chemotherapy tumor histology, and prognostic group presentation.

PMID- 19741570
TI  - Support for the involvement of the KCNK2 gene in major depressive disorder and
      response to antidepressant treatment.
AB  - OBJECTIVE: The aim of this study was to examine the associations between genetic
      variations in the human KCNK2 gene and major depressive disorder (MDD) and
      response to antidepressant treatment. METHOD: Four hundred and forty-nine
      patients with MDD and 421 normal controls were included in the study; among the
      MDD patients, 158 were further followed-up for 8 weeks to assess their response
      to antidepressant treatment. Five polymorphisms (rs12131478, rs6667764,
      rs10494994, rs11583745 and rs6686529) of the KCNK2 gene were investigated in
      terms of their association with MDD and antidepressant treatment efficacy.
      RESULTS: The genotype frequency of rs6686529 differed significantly between the
      MDD patients and controls (uncorrected P = 0.00052) and remained statistically
      significant after correction for multiple comparisons. Individuals with
      homozygous genotypes (CC or GG) showed greater susceptibility to MDD than those
      with heterozygous genotypes, indicating a possible heterosis effect of the
      polymorphism on MDD. In addition, this polymorphism also affected the efficacy of
      antidepressant treatment: the CC carriers had a greater probability of achieving
      remission after 8 weeks of treatment than the G-allele carriers [odds ratio =
      2.55 (95% confidence interval = 1.11-5.88)]. CONCLUSION: Our findings are in line
      with those of animal studies, and show that KCNK2 is related to the
      susceptibility to MDD, and involved in antidepressant treatment response.
      However, the finding of heterosis association of rs6686529 and MDD may be
      mechanistic, and further replication studies will be essential.

PMID- 19741571
TI  - The management of ruptured abdominal aortic aneurysms.

PMID- 19741572
TI  - Stent-graft use in urgent and emergent AAA management.
AB  - The use of stent grafts in the treatment of ruptured aortic aneurysm, abdominal
      (AAA) may reduce mortality associated with this process through its dramatic
      alteration of the surgical technique employed. Advantages of endovascular repair
      include the ability to perform the procedure under local anesthesia, decreased
      physiologic stress of avoiding a laparotomy and avoiding collateral damage during
      open repair. Criticisms of this technique include additional preoperative time
      spent obtaining appropriate imaging, the necessity for specialized products and
      personnel required to perform the procedure, and late complications such as
      abdominal compartment syndrome. Current data regarding a survival advantage
      appear favorable but flawed, highlighting the need for prospective randomized
      trial. Three trials are currently underway with the largest, the IMPROVE trial,
      the most likely to yield definitive evidence.

PMID- 19741573
TI  - Mortality of ruptured abdominal aortic aneurysm with selective use of
      endovascular repair.
AB  - The aim of this review was to examine the results over a seven-year period of
      treatment for ruptured abdominal aortic aneurysm (RAAA). From 2002 on, our
      tertiary referral centre offered both open and endovascular (EVAR) treatment
      modalities for RAAA. All patients with a proven RAAA who were admitted into our
      hospital were included. Primary outcome measure was surgical mortality. In total
      261 patients were admitted with suspicion of acute AAA. Of these, 175 (67%) had a
      RAAA, confirmed by computed tomography-scanning or at laparotomy. One hundred and
      fifty-nine patients (90.9%) were treated, 114 by open repair and 45 by EVAR.
      Overall mortality of patients treated was 25.2%, with an open repair mortality of
      27.2%, and EVAR mortality of 20%. EVAR was used more often in patients who were
      hemodynamically more stable. Evaluation for EVAR and treatment by EVAR increased
      during the study period. Overall mortality rate for treatment of RAAA in our
      centre was 25% over the seven-year study period.

PMID- 19741574
TI  - Choice of treatment for the patient with urgent AAA: practical tips.
AB  - Since the first successful attempts of emergency endovascular aneurysm repair
      (eEVAR) for patients with ruptured AAAs in the mid 1990s, surgeons have had to
      decide whether to treat patients by conventional open surgery or by minimally
      invasive but technically more demanding eEVAR. To date, selection of patients for
      eEVAR is still heavily debated and factors like hemodynamic instability, fear of
      treatment delay for patient transfer or imaging procedures and logistic issues
      often lead to the exclusion of anatomically suitable patients from eEVAR.
      However, these adverse factors may be overcome by adherence to an appropriate
      (intention-to-treat) protocol employing the use of a hypotensive hemostatic
      approach, transfemoral aortic balloon occlusion technique (when needed),
      different types of devices and an appropriate plan to resolve logistic issues,
      leaving anatomic suitability as the single most important determinant of
      suitability for EVAR.

PMID- 19741575
TI  - The influence of statins on the expansion rate and rupture risk of abdominal
      aortic aneurysms.
AB  - Abdominal aortic aneurysms (AAA) have a prevalence between 1.3-8.9% in men and
      1.0-2.2% in women aged above 55 years. Furthermore, AAA cause 1-3% of all deaths
      among men aged 65-85 years in developed countries. As the disorder is invariably
      associated with severe atherosclerotic damage of the arterial wall, it has
      traditionally been regarded as a direct consequence of generalized
      atherosclerotic disease. In patients with occlusive aortic disease, dyslipidemia
      is a well established risk factor. However, in patients with aneursymatic aortic
      disease, the association between dyslipidemia and the development of AAA is less
      clear. Large clinical trials in patients with cardiac and peripheral arterial
      disease have shown the strong relation between dyslipidemia, statin therapy and
      the risk of cardiovascular disease. Importantly, the effects of statin therapy
      were still present irrespective of the decrease in serum cholesterol levels.
      These findings resulted in the discussion of potential non-lipid lowering effects
      of statin therapy. These ''pleiotropic effects'' compose a diversity of cellular
      events which have an effect on several components of the arterial wall,
      including: 1) endothelial cells; 2) smooth muscle cells; 3) platelets; 4)
      monocytes/macrophages; and 5) the process of inflammation. In the general
      population the role of dyslipidemia as an independent risk factor for AAA is
      debated. However, as patients with AAA frequently have concomitant arterial
      disease, statin therapy is often recommended. As a result, the non-lipid lowering
      effects of statins on aneurysm expansion rate are hardly studied, and most
      evidence comes from experimental and animal studies. In the current review
      article we provide an overview of all available literature on the effects of
      dyslipidemia, statin therapy and the risk of AAA expansion and rupture. In the
      first part we summarize all population-based studies that investigated the
      relation between hypercholesterolemia and the development of AAA. In the second
      part, the available literature regarding the effects of statins on aneurysm
      growth, expansion rate and the risk of rupture is summarized, including in vitro,
      animal and clinical human studies.

PMID- 19741576
TI  - Endovascular treatment for ruptured abdominal aortic aneurysm. Review of
      literature.
AB  - Endovascular repair (EVAR) has produced increasing interest in the treatment of
      ruptured abdominal aortic aneurysms (rAAAs). Experiences to support EVAR as first
      approach for patients with rAAA is drawn from three sources: results of single
      centre series, systematic reviews, and population-based studies. In order to
      validate EVAR, this technique was compared to open repair (OR), considered as the
      conventional treatment. These studies are heterogeneous, and often failed to
      demonstrate any significant difference between EVAR and OR. More recently, some
      population-based studies from the USA suggested advantages of EVAR over OR with
      regard to 30-day mortality and morbidity. Some bias have influenced the reported
      RESULTS: Criteria for choice of EVAR varied across the studies according to the
      policy of the authors. Therefore, any meta-analysis should be interpreted with
      caution. Patients' conditions have directed the authors towards a technique
      instead of the other, i.e. pathophysiological factors of the patients, and
      anatomical conditions of the AAAs. Availability of the required endovascular
      equipment and trained staff allows EVAR and not always were present. Currently,
      according to the literature the role of EVAR in the management of rAAAs must to
      be further checked. Randomized trials could provide the evidence to define
      adequate indication to EVAR. EVAR could play an important role in the treatment
      of rAAAs, providing adequate selection of cases suitable for this technique.

PMID- 19741577
TI  - EVAR for ruptured AAAs -- Do we need randomized controlled trials?
AB  - Endovascular abdominal aortic aneurysm (EVAR) repair has an established role in
      elective management of abdominal aortic aneurysms (AAA). The application of EVAR
      to ruptured AAAs (rAAA) is evolving and developing a strong evidence base in
      selected patients. Although EVAR has been utilized to manage rAAA for greater
      than ten years, to-date no randomized study has been completed to confirm
      superiority over traditional open surgical repair. Randomized controlled trials
      (RCTs) allow unbiased objective comparison of two techniques and are the most
      powerful scientific instrument available for clinical assessment; they form the
      corner-stone of surgical evidence-based practice. In light of current
      understanding, the role of a RCT to compare emergency EVAR (eEVAR) with open
      surgery has been challenged. Whether an RCT is necessary, is ethical or can mimic
      routine clinical practice are questions open to debate. This review presents the
      current best evidence for eEVAR, the arguments for and against an RCT, and
      details current and prospective clinical trials designed to identify the optimal
      management of rAAA.

PMID- 19741578
TI  - Below-the-knee revascularization. Advanced techniques.
AB  - This review summarizes new developments in revascularization and advanced
      techniques to treat lesions below the knee (BTK). The primary goal of
      endovascular therapy is the re-establishment of pulsatile, straight-line flow to
      the foot. This treatment results in relieving ischemic pain, healing of
      (neuro)ischemic ulcers, preventing limb loss, improving quality of life and
      potentially prolong survival. Balloon angioplasty is the currently established
      therapy, bare-metal stents are reserved for failed percutaneous transluminal
      angioplasty (PTA). Novel devices such as laser, excisional and rotational
      atherectomy systems, drug eluting stents or drug coated balloons still lack data
      demonstrating improved efficacy compared to conventional balloon angioplasty. The
      typical patient group of complex below-the-knee lesions represents an increasing
      population due to the increasing prevalence of diabetes and end-stage renal
      failure. Excellent acute technical success rates above 90%, a low frequency of
      complications, and high limb salvage rate of about 95% even in patients with long
      segment and diffuse disease seem to justify a more widespread use of endovascular
      therapy in tibial arteries. However, the current results of balloon angioplasty
      studies show a 1-year restenosis rate between 30% for short stenoses treatment
      and up to 80% following recanalization of an occlusion.

PMID- 19741579
TI  - New stents for SFA.
AB  - Endovascular stent implantation was introduced to femoropopliteal procedures
      almost two decades ago. Initial results with balloon-expandable stainless steel
      stents and self expanding Elgiloy stents, however, were disappointing. In
      particular, recurrence rates after long-segment femoropopliteal stenting were
      rather high, in the range of 60% to 80% at 1 year. After years of stagnation,
      recent developments in femoropopliteal stent technology have been promising. Self
      expanding nitinol stents have been evaluated in several prospective studies.
      Initial problems with stent fractures seem to be resolved using second-generation
      devices. The second generation of Nitinol stents have an enhanced flexibility
      particularly also in axial direction due to a reduction of cell interconnections
      and a more spiral orientation of the interconnections. However, until now there
      is no proof of any impact of the stent design on restenosis rate. Otherwise,
      stenting has been shown to be beneficial compared to balloon angioplasty
      especially in longer femoropopliteal lesions. The superior fracture resistance of
      the latest stent generation in combination with the production of long nitinol
      stents of up to 20 cm in length allow that more difficult and complex lesions can
      be treated endovascularly. The main unresolved problem with femoropopliteal
      stenting is the treatment of instent restenosis. Future concepts to further
      improve long-term patency after femoropopliteal stenting are therefore under
      investigation, including drug-eluting stents (DES), biodegradable stents, and
      coated stent-grafts. Stent grafts appear to be a viable option for the treatment
      of complex superficial femoral artery lesions, with comparable outcomes to
      prosthetic above-knee femoropopliteal bypass surgery. Concerning DES, we have to
      wait for the results of the ongoing studies.

PMID- 19741580
TI  - Chronic critical limb ischemia: European experiences.
AB  - Chronic critical limb ischemia still poses a substantial threat to both limb and
      life of the affected patients since these patients suffer typically also from
      associated cardiac and cerebrovascular disease and other severe comorbidities.
      Due to improved secondary prevention strategies and dedicated technical
      innovation, however, clinical outcomes have improved in the recent years. Purpose
      of this article is to provide a balanced discussion of contemporary treatment
      concepts for patients with critical limb ischemia with a focus on arterial
      revascularization.

PMID- 19741581
TI  - Effects of simvastatin on systemic inflammatory responses after cardiopulmonary
      bypass.
AB  - AIM: Cardiopulmonary bypass is associated with a complex systemic inflammatory
      response and the extent of their increase has been correlated with the
      development of postoperative complications. Recent studies suggest that treatment
      with statins is associated with a significant and marked decrease in inflammation
      associated variables such as cytokines. Therefore, we investigated the effects of
      preoperative simvastatin treatment on systemic inflammatory response and
      perioperative morbidity after cardiopulmonary bypass. METHODS: A prospective,
      randomized study, was designed. Forty-four subjects undergoing elective coronary
      artery bypass grafting who fulfilled the inclusion criteria were randomized to
      treatment with simvastatin (20 mg/day, group A, N. 22) or control (group B, N.
      22) before surgery. Plasma levels of interleukins (IL-6, IL-8, TNF-alpha), and
      systemic inflammatory response score (SIRS) were measured during the surgical
      intervention and over the following 48 postoperative hours. Cytokine levels were
      measured by enzyme-linked assays from plasma samples obtained at specific time
      points pre- and post-operation. RESULTS: In both groups the serum levels of the
      proinflammatory cytokines (IL-6, IL-8, TNF-alpha), and leukocytes, and the SIRS
      score increased significantly over the baseline, though no significant
      differences were observed between the two groups. The preoperative and
      postoperative course did not differ between both groups. CONCLUSIONS: In patients
      undergoing coronary artery bypass grafting with cardiopulmonary bypass, the
      administration of simvastatin doses not produce any changes in the inflammatory
      response as measured by the levels of IL-6, IL-8, TNF-alpha and SIRS score, nor
      does it reduce the complications after cardiac surgery.

PMID- 19741583
TI  - New opportunities for the management of cancer-related bone complications.

PMID- 19741582
TI  - Impact of the definition of renal dysfunction on EuroSCORE performance.
AB  - AIM: Renal dysfunction is an important variable in the EuroSCORE (European System
      for Cardiac Operative Risk Evaluation) model and is currently defined as
      creatinine >200 mmol/L. The aim of this study was to examine whether using other
      definitions of renal dysfunction could improve the predictive ability of the
      EuroSCORE. METHODS: Between January 2004 and January 2006, 1 205 patients
      underwent cardiac surgery. Their preoperative glomerular filtration rate and
      EuroSCORE were calculated. Four recalibrated EuroSCORE models were constructed
      using 1) creatinine as a binary variable; 2) creatinine as a continuous variable;
      3) glomerular filtration rate as a categorical variable; or 4) glomerular
      filtration rate as a continuous variable. The predictive ability of these models
      was assessed using receiver operating characteristic curve analysis. RESULTS:
      Hospital mortality was 4% (N.=47). Receiver operating characteristic curve values
      were: 0.78 for the original EuroSCORE, 0.80 for the recalibrated binary
      creatinine model, 0.83 for the continuous creatinine model, 0.83 for the
      categorical glomerular filtration rate model, and 0.82 for the continuous
      glomerular filtration rate model. CONCLUSIONS: The use of creatinine as a
      continuous variable or glomerular filtration rate as a categorical or continuous
      variable improves the predictive accuracy of the EuroSCORE model for hospital
      mortality. Given the increasing incidence of preoperative renal dysfunction and
      its impact on hospital mortality, future risk stratification models should
      include continuous creatinine or glomerular filtration rate rather than
      creatinine as a binary variable.

PMID- 19741586
TI  - Assay for pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI)
      in plants.
AB  - To perceive potential pathogens in their environment, plants use pattern
      recognition receptors (PRRs) present on their plasma membranes. PRRs recognize
      conserved microbial features called pathogen-associated molecular patterns
      (PAMPs) and this detection leads to PAMP-triggered immunity (PTI), which
      effectively prevents colonization of plant tissues by non-pathogens(1,2). The
      most well studied system in PTI is the FLS2-dependent pathway(3). FLS2 recognizes
      the PAMP flg22 that is a component of bacterial flagellin. Successful pathogens
      possess virulence factors or effectors that can suppress PTI and allow the
      pathogen to cause disease(1). Some plants in turn possess resistance genes that
      detect effectors or their activity, which leads to effector-triggered immunity
      (ETI)(2). We describe a cell death-based assay for PTI modified from Oh and
      Collmer(4). The assay was standardized in N. benthamiana, which is being used
      increasingly as a model system for the study of plant-pathogen interactions(5).
      PTI is induced by infiltration of a non-pathogenic bacterial strain into leaves.
      Seven hours later, a bacterial strain that either causes disease or which
      activates ETI is infiltrated into an area overlapping the original infiltration
      zone. PTI induced by the first infiltration is able to delay or prevent the
      appearance of cell death due to the second challenge infiltration. Conversely,
      the appearance of cell death in the overlapping area of inoculation indicates a
      breakdown of PTI. Four different combinations of inducers of PTI and challenge
      inoculations were standardized (Table 1). The assay was tested on non-silenced N.
      benthamiana plants that served as the control and plants silenced for FLS2 that
      were predicted to be compromised in their ability to develop PTI.

PMID- 19741587
TI  - Anti-glomerular basement membrane autoantibodies against different target
      antigens are associated with disease severity.
AB  - Anti-glomerular basement membrane (GBM) autoantibodies are pathogenic in the
      development of anti-GBM disease. The main target antigen is the non-collagenous 1
      domain (NC1) of collagen alpha3(IV); however, most antibodies can recognize the
      NC1 of collagens alpha1, alpha2, alpha4 and alpha5(IV). In this study, we
      analyzed the target antigens of anti-GBM autoantibodies to determine their
      relationship to the severity of renal damage. Natural anti-GBM autoantibodies
      were purified from 10 healthy individuals and from 57 patients with anti-GBM
      disease who were divided into groups based on the degree of renal damage defined
      by their serum creatinine at the time of diagnosis. We found that the sera of all
      57 patients recognized alpha3(IV)NC1, while 23, 20, 28, and 48 patients also
      recognized the NC1 of collagens alpha1, alpha2, alpha4, and alpha5(IV),
      respectively. Natural anti-GBM autoantibodies recognized the NC1 of collagens
      alpha3 and alpha4(IV). The sera of 7 patients with the lowest level of renal
      damage mainly recognized the NC1 of collagens alpha3 and alpha5(IV). In the 20
      patients with moderate and the 30 with severe renal damage, all five target
      antigens could be detected and most sera recognized three to five different alpha
      chains simultaneously. Regression analysis showed that only the level of
      autoantibodies against the NC1 of collagen alpha3(IV) was a significant
      independent risk factor for higher serum creatinine on diagnosis. Our study shows
      that autoantibodies to the NC1 of collagen alpha3(IV) were crucial in causing
      renal damage. Inter- and intra-molecular epitope spreading can occur during the
      development of human anti-GBM disease.

PMID- 19741588
TI  - WITHDRAWN: Endothelium in the allograft.
AB  - The paper entitled "Endothelium in the allograft" by Bryan N Becker et al, which
      was published online on 9 September 2009, has been withdrawn at the authors'
      request. Kidney International advance online publication, 9 September 2009;
      doi:10.1038/ki.2009.333.

PMID- 19741589
TI  - Mediterranean diets are associated with a lower incidence of metabolic syndrome
      one year following renal transplantation.
AB  - Considering the high prevalence of metabolic syndrome and its association with
      cardiovascular mortality, we prospectively evaluated the role of diet in the
      incidence of metabolic syndrome in renal transplant recipients. Our prospective
      cohort of 160 adult renal allograft recipients was followed for 1 year and had no
      existing metabolic syndrome or diabetes mellitus. Routine dietary intakes were
      assessed with food-frequency questionnaires, and metabolic syndrome was defined
      according to the Adult Treatment Panel III guidelines. We identified 3 major
      patterns by factor analysis, consisting of those recipients predominantly
      consuming fats and sugars, those predominantly consuming whole grain, and the
      Mediterranean diet. When analyzed by multivariable logistic regression and after
      controlling for potential confounders, subjects in the highest tertile of scores
      for the Mediterranean diet had a significantly lower odds of metabolic syndrome
      than those in the lowest tertile. Subjects in the highest tertile of scores for
      consuming fats and sugars had significantly greater odds of metabolic syndrome
      compared with those in the lowest tertile. Our study shows that the Mediterranean
      dietary pattern is associated with a reduced risk of metabolic syndrome in renal
      transplant recipients.

PMID- 19741590
TI  - Outcomes following diagnosis of acute renal failure in U.S. veterans: focus on
      acute tubular necrosis.
AB  - When patients develop acute kidney injury, a small fraction of them will develop
      end-stage renal disease later. The severity of renal impairment in the remaining
      patients is uncertain because studies have not carefully examined renal function
      over time or the precise timing of entry into a late stage of chronic kidney
      disease. To determine these factors, we used a United States Department of
      Veterans Affairs database to ascertain long-term renal function in 113,272
      patients. Of these, 44,377 had established chronic kidney disease and were
      analyzed separately. A cohort of 63,491 patients was hospitalized for acute
      myocardial infarction or pneumonia and designated as controls. The remaining
      5,404 patients had diagnostic codes indicating acute renal failure or acute
      tubular necrosis. Serum creatinine, estimated glomerular filtration rates, and
      dates of death over a 75-month period were followed. Renal function deteriorated
      over time in all groups, but with significantly greater severity in those who had
      acute renal failure and acute tubular necrosis compared to controls. Patients
      with acute kidney injury, especially those with acute tubular necrosis, were more
      likely than controls to enter stage 4 chronic kidney disease, but this entry time
      was similar to that of patients who initially had chronic kidney disease. The
      risk of death was elevated in those with acute kidney injury and chronic kidney
      disease compared to controls after accounting for covariates. We found that
      patients who had an episode of acute tubular necrosis were at high risk for the
      development of stage 4 disease and had a reduced survival time when compared to
      control patients.

PMID- 19741591
TI  - Environmental enrichment reduces cocaine seeking and reinstatement induced by
      cues and stress but not by cocaine.
AB  - Whereas earlier studies have focused on the preventive effects of enriched
      environments (EE) in drug addiction, in a recent study we suggested that EE can
      also have 'curative' effects. In fact, we found that cocaine addiction-related
      behaviors can be eliminated by housing cocaine-treated mice in EE during periods
      of forced abstinence. However, those results were obtained with two simple models
      of addiction, conditioned place preference (CPP), and behavioral sensitization.
      In this study, we used intravenous drug self-administration procedures in rats to
      further investigate the beneficial effects of EE on cocaine addiction in a
      reinstatement model of relapse. Singly housed rats learned to self-administer
      cocaine during 10 consecutive daily sessions (0.6 mg/injection, 6 h/day). They
      were then housed three per cage in either standard environments (SE) or EE and
      were kept abstinent in the animal facility until testing for extinction and
      reinstatement. We found that 30 days of EE significantly and consistently reduced
      cocaine seeking during a 6-h extinction session. In addition, EE significantly
      reduced cue- and stress-induced reinstatement. Surprisingly, given our earlier
      results in mice with CPP, EE did not reduce cocaine-induced reinstatement
      regardless of the level of exposure to cocaine and the duration of the period of
      abstinence and exposure to EE. Altogether, these results support the hypothesis
      that EE can reduce cocaine-induced craving and highlight the importance of
      positive life conditions in facilitating abstinence and preventing relapse to
      cocaine addiction.

PMID- 19741592
TI  - Atypical depression: useful concept, but it's time to revise the DSM-IV criteria.
AB  - Stewart et al (2009) have outlined the evidence in support of the validity of the
      DSM-IV definition of the 'With Atypical Features' episode specifier. Although
      recognizing the historical significance and clinical utility of the concept of
      atypical depression, this article takes issue with the DSM-IV criteria. It is
      concluded that mood reactivity, the A or obligative criterion, is neither
      significantly associated with the other symptomatic criteria nor useful to
      diagnose atypical depression, and thus should be eliminated. Problems with
      operationalization, specification, and reliability of ratings of the diagnostic
      criteria further limit validity. Despite these limitations in classification,
      many of the features associated with atypical depression are linked to an early
      onset of affective illness, including trait-like interpersonal sensitivity,
      comorbid social anxiety and agoraphobia, a history of childhood physical or
      sexual trauma, and indicators of the 'soft' side of the bipolar spectrum.
      Neurophysiologic studies also suggest that chronic, early-onset atypical
      depressions differ from both melancholia and normality. Re-analyses of the
      Columbia group's seminal studies suggest that preferential response to phenelzine
      vs imipramine--arguably the strongest validator of atypical depression--similarly
      appears to be limited to patients with chronic, early-onset syndromes. The
      criteria for atypical depression need to be revised in DSM-V, including
      sharpening the operational definitions for the specific symptoms. The importance
      of age of onset and comorbid anxiety warrant further study. Research examining
      the validity of a subform of atypical depression characterized by trait-like
      interpersonal sensitivity and a chronic, early-onset course may further enhance
      the clinical utility of the DSM-V classification.

PMID- 19741593
TI  - D-cycloserine deters reacquisition of cocaine self-administration by augmenting
      extinction learning.
AB  - Augmentation of cue exposure (extinction) therapy with cognitive-enhancing
      pharmacotherapy may offer an effective strategy to combat cocaine relapse. To
      investigate this possibility at the preclinical level, rats and squirrel monkeys
      were trained to self-administer cocaine paired with a brief visual cue. Lever
      pressing was subsequently extinguished by withholding cocaine injections while
      maintaining response-contingent presentations of the cue. The glycine partial
      agonist D-cycloserine (DCS; 15 and 30 mg/kg in rats, 3 and 10 mg/kg in monkeys)
      was evaluated for its effects on the rate of extinction and subsequent
      reacquisition of cocaine self-administration. Compared with vehicle, pretreatment
      with 30 mg/kg DCS 0.5 h before extinction training reduced the number of
      responses and latency to reach the extinction criterion in rats, but neither dose
      of DCS altered these measures in monkeys. In both species, pretreatment with the
      higher dose of DCS before extinction training significantly attenuated
      reacquisition of cocaine self-administration compared with either extinction
      training in the absence of DCS or DCS in the absence of explicit extinction.
      Furthermore, treatment with 30 mg/kg DCS accompanied by brief handling (a stress
      induction) immediately after but not 6 h after extinction training attenuated
      reacquisition of cocaine self-administration in rats. No adverse effects of 10
      mg/kg DCS were evident in quantitative observational studies in monkeys. The
      results suggest that DCS augmented consolidation of extinction learning to deter
      reacquisition of cocaine self-administration in rats and monkeys. The results
      suggest that DCS combined with exposure therapy may constitute a rational
      strategy for the clinical management of cocaine relapse.

PMID- 19741594
TI  - Dopamine agonists diminish value sensitivity of the orbitofrontal cortex: a
      trigger for pathological gambling in Parkinson's disease?
AB  - The neurobehavioral underpinnings of pathological gambling are not well
      understood. Insight might be gained by understanding pharmacological effects on
      the reward system in patients with Parkinson's disease (PD). Treatment with
      dopamine agonists (DAs) has been associated with pathological gambling in PD
      patients. However, how DAs are involved in the development of this form of
      addiction is unknown. We tested the hypothesis that tonic stimulation of dopamine
      receptors specifically desensitizes the dopaminergic reward system by preventing
      decreases in dopaminergic transmission that occurs with negative feedback. Using
      functional magnetic resonance imaging, we studied PD patients during three
      sessions of a probabilistic reward task in random order: off medication, after
      levodopa (LD) treatment, and after an equivalent dose of DA (pramipexole). For
      each trial, a reward prediction error value was computed using outcome, stake,
      and probability. Pramipexole specifically changed activity of the orbitofrontal
      cortex (OFC) in two ways that were both associated with increased risk taking in
      an out-of-magnet task. Outcome-induced activations were generally higher with
      pramipexole compared with LD or off medication. In addition, only pramipexole
      greatly diminished trial-by-trial correlation with reward prediction error
      values. Further analysis yielded that this resulted mainly from impaired
      deactivation in trials with negative errors in reward prediction. We propose that
      DAs prevent pauses in dopamine transmission and thereby impair the negative
      reinforcing effect of losing. Our findings raise the question of whether
      pathological gambling may in part stem from an impaired capacity of the OFC to
      guide behavior when facing negative consequences.

PMID- 19741595
TI  - The development of intestinal lymphoid tissues at the interface of self and
      microbiota.
AB  - Intestinal lymphoid tissues face the challenging task of inducing adaptive
      immunity to pathogens, yet maintaining homeostasis with the enormous commensal
      microbiota. To that aim, the ancient partnership between self and flora has
      resulted in the generation of a unique set of lymphoid tissues capable of
      constant large-scale reformatting. A first set of lymphoid tissues, the
      mesenteric lymph nodes and Peyer's patches, are programmed to develop in the
      sterile environment of the fetus, whereas a second set of lymphoid tissues, the
      tertiary lymphoid tissues, are induced to form by the microbiota and
      inflammation. The diversity of intestinal lymphoid tissues confers the
      flexibility required to adapt the number of immune inductive sites to the size of
      the flora and the extent of the pathogenic threat. The result is a functional
      superorganism combining self and microbes for the best possible symbiosis.

PMID- 19741596
TI  - Gut-associated lymphoid tissue contains the molecular machinery to support T-cell
      dependent and T-cell-independent class switch recombination.
AB  - A PRoliferation-Inducing Ligand (APRIL) is a secreted cytokine member of the
      tumor necrosis factor family. It is a B-cell survival factor that also induces
      class switch recombination (CSR) toward immunoglobulin A (IgA), independent of T
      cells. It is therefore an important contributor to the maintenance of the mucosal
      immunological barrier, which has been linked to a putative extrafollicular
      inductive phase of the IgA response in lamina propria. By immunohistochemistry
      (IHC) and quantitative real-time PCR (qRT-PCR) on microdissected tissue from
      normal human gut, we observed APRIL expression, together with TACI (transmembrane
      activator and CAML interactor) and BCMA (B-cell maturation antigen), in gut
      associated lymphoid tissue (GALT), lamina propria, and in the epithelium of
      stomach, small and large intestine, and rectum. However, no activation-induced
      cytidine deaminase (AID) expression (an absolute requirement for class switching)
      was detected in lamina propria by IHC or qRT-PCR. APRIL and its receptors were
      only observed alongside AID in GALT, showing that GALT contains the apparatus to
      support both T-independent and T-dependent routes to IgA CSR.

PMID- 19741597
TI  - CXCL13 expression in the gut promotes accumulation of IL-22-producing lymphoid
      tissue-inducer cells, and formation of isolated lymphoid follicles.
AB  - The chemokine CXCL13 is overexpressed in the intestine during inflammation. To
      mimic this condition, we created transgenic mice-expressing CXCL13 in intestinal
      epithelial cells. CXCL13 expression promoted a marked increase in the number of B
      cells in the lamina propria and an increase in the size and number of lymphoid
      follicles in the small intestine. Surprisingly, these changes were associated
      with a marked increase in the numbers of RORgammat(+)NKp46(-)CD3(-)CD4(+) and
      RORgammat(+)NKp46(+) cells. The RORgammat(+)NKp46(-)CD3(-)CD4(+) cells expressed
      CXCR5, the receptor for CXCL13, and other markers of lymphoid tissue-inducer
      cells, such as LTalpha, LTbeta, and TNF-related activation-induced cytokine
      (TRANCE). RORgammat(+)NKp46(-)CD3(-)CD4(+) gut LTi cells produced IL-22, a
      cytokine implicated in epithelial repair; and expressed the IL-23 receptor, a key
      regulator of IL-22 production. These results suggest that overexpression of
      CXCL13 in the intestine during inflammatory conditions favors mobilization of B
      cells and of LTi and NK cells with immunomodulatory and reparative functions.

PMID- 19741598
TI  - PD-L1 and PD-L2 modulate airway inflammation and iNKT-cell-dependent airway
      hyperreactivity in opposing directions.
AB  - Interactions of the inhibitory receptor programmed death-1 (PD-1) with its
      ligands, programmed death ligand (PD-L)1 and PD-L2, regulate T-cell activation
      and tolerance. In this study, we investigated the role of PD-L1 and PD-L2 in
      regulating invariant natural killer T (iNKT)-cell-mediated airway hyperreactivity
      (AHR) in a murine model of asthma. We found that the severity of AHR and airway
      inflammation is significantly greater in PD-L2(-/-) mice compared with wild-type
      mice after either ovalbumin (OVA) sensitization and challenge or administration
      of alpha-galactosylceramide (alpha-GalCer). iNKT cells from PD-L2(-/-) mice
      produced significantly more interleukin (IL)-4 than iNKT cells from control mice.
      Moreover, blockade of PD-L2 interactions of wild-type iNKT cells in vitro with
      monoclonal antibodies (mAbs) resulted in significantly enhanced levels of IL-4
      production. In contrast, PD-L1(-/-) mice showed significantly reduced AHR and
      enhanced production of interferon-gamma (IFN-gamma) by iNKT cells. iNKT-deficient
      Jalpha18(-/-) mice reconstituted with iNKT cells from PD-L2(-/-) mice developed
      high levels of AHR, whereas mice reconstituted with iNKT cells from PD-L1(-/-)
      mice developed lower levels of AHR compared with control. As PD-L2 is not
      expressed on iNKT cells but rather is expressed on lung dendritic cells (DCs), in
      which its expression is upregulated by allergen challenge or IL-4, these findings
      suggest an important role of PD-L2 on lung DCs in modulating asthma pathogenesis.
      These studies also indicate that PD-L1 and PD-L2 have important but opposing
      roles in the regulation of AHR and iNKT-cell-mediated activation.

PMID- 19741599
TI  - Lymphoid tissue inducer cells: bridges between the ancient innate and the modern
      adaptive immune systems.
AB  - Phylogeny indicates that adaptive immunity evolved first in diffusely distributed
      lymphoid tissues found in the lamina propria (LP) of the gut. B follicular
      structures appeared later, probably initially in isolated lymphoid follicles in
      the LP and then in organized lymphoid tissues such as lymph nodes and Peyer's
      patches. The development of these new lymphoid structures was enabled by gene
      duplication and evolution of new tumor necrosis family members. Here, we argue
      that lymphoid tissue inducer cells (LTis) had a pivotal role, not only in the
      development of organized lymphoid structures, but also in the subsequent genesis
      of the CD4-dependent class-switched memory antibody responses. In this review, we
      concentrate on the latter function: the sustenance by LTis of CD4 T-cell
      responses for protective immunity.

PMID- 19741600
TI  - Repeated vaginal administration of trimeric HIV-1 clade C gp140 induces serum and
      mucosal antibody responses.
AB  - Vaccine-mediated prevention of primary infection with human immunodeficiency
      virus (HIV) may require the sustained production of antibody at mucosal portals
      of entry. Here, we describe a novel approach of repeated mucosal immunization by
      delivering an HIV-1 envelope glycoprotein (gp) in a gel formulated for
      intravaginal delivery. Rabbits were immunized over one to three 19-day cycles of
      intravaginal dosing with soluble recombinant trimeric HIV-1 clade C gp140
      administered in Carbopol gel. The formulation was well tolerated. A single
      immunization cycle induced immunoglobulin G (IgG) antibody detected in the serum
      and female genital tract, and titers were boosted on further immunization.
      Vaccine-induced serum antibodies neutralized the infectivity of a pseudovirus
      carrying a heterologous clade C envelope. Our data prove the concept that
      repeated exposure of the female genital tract to HIV envelope can induce
      mucosally detectable antibody.

PMID- 19741601
TI  - CCR2-dependent intraepithelial lymphocytes mediate inflammatory gut pathology
      during Toxoplasma gondii infection.
AB  - Mice of the C57BL/6 strain develop acute ileal inflammation after infection with
      the protozoan parasite Toxoplasma gondii. This pathology resembles many key
      features of human Crohn's disease, including a Th1 cytokine profile with high
      levels of interferon gamma (IFN-gamma), interleukin 12 (IL)-12, and tumor
      necrosis factor alpha (TNF)-alpha, presence of pathogenic CD4(+) T cells, and
      infiltration of gut flora into inflammed tissue. Using CCR2(-/-) mice, we
      identify a role for this chemokine receptor in the pathogenesis of inflammatory
      pathology during T. gondii infection. Lack of chemokine (C-C motif) receptor 2
      (CCR2) was associated with low levels of CD103(+) T lymphocytes in the
      intraepithelial compartment, Peyer's patch, and lamina propria relative to wild
      type animals. Adoptive transfer of wild-type, but not IFN-gamma(-/-),
      intraepithelial T lymphocytes converted CCR2 knockout mice from a resistant to
      susceptible phenotype with respect to parasite-triggered inflammatory gut
      pathology. These results for the first time show a role for intraepithelial T
      lymphocytes in pathogenesis of ileitis triggered by a microbial pathogen.

PMID- 19741602
TI  - Diverse regulatory pathways for IgA synthesis in the gut.
AB  - Immunoglobulin (Ig) A is the most abundant antibody isotype in mucosal
      secretions. In this study we summarize recent advances in our understanding of
      the compartments and mechanisms of intestinal IgA synthesis. We discuss the
      pathways leading to the generation of IgA(+) B cells in follicular and extra
      follicular structures, by T-cell-dependent and T-cell-independent mechanisms.

PMID- 19741603
TI  - Nasal DNA-MVA SIV vaccination provides more significant protection from
      progression to AIDS than a similar intramuscular vaccination.
AB  - Preventive human immunodeficiency virus (HIV) vaccination may require induction
      of virus-specific immune responses at mucosal sites to contain viral infection
      locally after exposure, as most HIV infections occur through mucosal surfaces. We
      compared the efficacy of an intranasal or intramuscular Simian immunodeficiency
      virus (SIV)+ interleukin (IL)-2+IL-15 DNA/SIV-MVA (modified vaccinia virus
      Ankara) vaccination in preventing disease progression in SIVmac251 intrarectally
      challenged rhesus macaques. SIV-specific rectal IgA responses were more
      significantly persistent in nasally vaccinated than in intramuscularly vaccinated
      animals. No significant differences were observed in the magnitude of systemic T
      cell responses between the two groups, although the nasal immunization induced
      more significant anti-SIV T-cell responses in the colorectal mucosa. After
      challenge, CD4(+) central memory (C(M)) T-cell preservation and significant
      disease-delay were observed in both vaccination groups. However, nasally
      vaccinated animals had more significant early preservation of circulating and
      colorectal CD4(+) C(M) T cells, of circulating CD4(+)/alpha4beta7(+) effector
      memory (E(M)) T cells, and a longer disease-free interval when compared with the
      intramuscularly vaccinated or control groups. Regardless of vaccination status,
      long-term viremia control and preservation of CD4(+) C(M) T cells was detected in
      animals with significantly higher systemic CD8(+)/tumor necrosis factor (TNF)
      alpha(+) and CD8(+)/interferon (IFN)-gamma(+) T-cell responses and higher SIV
      specific CD4(+)/IL-2(+) responses in colorectal T cells.

PMID- 19741604
TI  - Potent and selective agonism of the melanocortin receptor 4 with MK-0493 does not
      induce weight loss in obese human subjects: energy intake predicts lack of weight
      loss efficacy.
AB  - MK-0493 is a novel, potent, and selective agonist of the melanocortin receptor 4
      (MC4R), one of the best-validated genetic targets and considered one of the most
      promising for the development of antiobesity therapeutics. An ad libitum energy
      intake model was qualified with excellent reproducibility: the geometric mean
      ratio (GMR) with 95% confidence interval (CI) for total energy intake over a
      period of 24 h for 30 mg sibutramine/placebo was 0.82 (0.76, 0.88), and for 10 mg
      sibutramine/placebo it was 0.98 (0.91, 1.05). MK-0493 showed a small and
      marginally significant effect on 24-h energy intake, whereas 30 mg of sibutramine
      caused a significant reduction in total 24-h energy intake; specifically, the GMR
      (95% CI) for 30 mg sibutramine/placebo was 0.79 (0.74, 0.85). MK-0493 was
      associated with modest weight reduction from baseline but had only small,
      statistically insignificant effects relative to placebo after 12 weeks in a fixed
      dose study and also after 18 weeks of stepped-titration dosing. We conclude that
      agonism of MC4R is not likely to represent a viable approach to the development
      of antiobesity therapeutics.

PMID- 19741605
TI  - Comparison of native E. coli and PEG asparaginase pharmacokinetics and
      pharmacodynamics in pediatric acute lymphoblastic leukemia.
AB  - Asparaginase (ASP) is used routinely in frontline clinical trials for the
      treatment of childhood acute lymphoblastic leukemia (ALL). The goals of this
      study were to assess the pharmacokinetics and pharmacodynamics of ASP and to
      mathematically model the dynamics between ASP and asparagine (ASN) in relapsed
      ALL. Forty children were randomized to receive either native or polyethylene
      glycolated (PEG) Escherichia coli ASP during reinduction therapy. Serial plasma
      ASP and ASN, cerebrospinal fluid (CSF) ASN, and serum anti-ASP antibody samples
      were collected. The ASP clearance was higher (P = 0.001) for native vs. PEG ASP.
      Patients with antibodies to PEG ASP had faster PEG ASP clearance (P = 0.004) than
      did antibody-negative patients. Patients who were positive for antibodies had
      higher CSF ASN concentrations than did those who were negative (P = 0.04). The
      modeling suggests that by modifying dosages, comparable ASN depletion is
      achievable with both preparations. At relapse, there were significant
      pharmacokinetic and pharmacodynamic differences attributable to ASP preparation
      and antibody status.

PMID- 19741606
TI  - Fgf8 morphogen gradient forms by a source-sink mechanism with freely diffusing
      molecules.
AB  - It is widely accepted that tissue differentiation and morphogenesis in
      multicellular organisms are regulated by tightly controlled concentration
      gradients of morphogens. How exactly these gradients are formed, however, remains
      unclear. Here we show that Fgf8 morphogen gradients in living zebrafish embryos
      are established and maintained by two essential factors: fast, free diffusion of
      single molecules away from the source through extracellular space, and a sink
      function of the receiving cells, regulated by receptor-mediated endocytosis.
      Evidence is provided by directly examining single molecules of Fgf8 in living
      tissue by fluorescence correlation spectroscopy, quantifying their local mobility
      and concentration with high precision. By changing the degree of uptake of Fgf8
      into its target cells, we are able to alter the shape of the Fgf8 gradient. Our
      results demonstrate that a freely diffusing morphogen can set up concentration
      gradients in a complex multicellular tissue by a simple source-sink mechanism.

PMID- 19741607
TI  - A luminal epithelial stem cell that is a cell of origin for prostate cancer.
AB  - In epithelial tissues, the lineage relationship between normal progenitor cells
      and cell type(s) of origin for cancer has been poorly understood. Here we show
      that a known regulator of prostate epithelial differentiation, the homeobox gene
      Nkx3-1, marks a stem cell population that functions during prostate regeneration.
      Genetic lineage-marking demonstrates that rare luminal cells that express Nkx3-1
      in the absence of testicular androgens (castration-resistant Nkx3-1-expressing
      cells, CARNs) are bipotential and can self-renew in vivo, and single-cell
      transplantation assays show that CARNs can reconstitute prostate ducts in renal
      grafts. Functional assays of Nkx3-1 mutant mice in serial prostate regeneration
      suggest that Nkx3-1 is required for stem cell maintenance. Furthermore, targeted
      deletion of the Pten tumour suppressor gene in CARNs results in rapid carcinoma
      formation after androgen-mediated regeneration. These observations indicate that
      CARNs represent a new luminal stem cell population that is an efficient target
      for oncogenic transformation in prostate cancer.

PMID- 19741608
TI  - Asymptomatic deer excrete infectious prions in faeces.
AB  - Infectious prion diseases-scrapie of sheep and chronic wasting disease (CWD) of
      several species in the deer family-are transmitted naturally within affected host
      populations. Although several possible sources of contagion have been identified
      in excretions and secretions from symptomatic animals, the biological importance
      of these sources in sustaining epidemics remains unclear. Here we show that
      asymptomatic CWD-infected mule deer (Odocoileus hemionus) excrete CWD prions in
      their faeces long before they develop clinical signs of prion disease.
      Intracerebral inoculation of irradiated deer faeces into transgenic mice
      overexpressing cervid prion protein (PrP) revealed infectivity in 14 of 15 faecal
      samples collected from five deer at 7-11 months before the onset of neurological
      disease. Although prion concentrations in deer faeces were considerably lower
      than in brain tissue from the same deer collected at the end of the disease, the
      estimated total infectious dose excreted in faeces by an infected deer over the
      disease course may approximate the total contained in a brain. Prolonged faecal
      prion excretion by infected deer provides a plausible natural mechanism that
      might explain the high incidence and efficient horizontal transmission of CWD
      within deer herds, as well as prion transmission among other susceptible cervids.

PMID- 19741610
TI  - DNA confidential.
AB  - As the cost of human genome sequencing plunges and large-scale genome-phenotype
      studies become possible, society should do more to reward those individuals who
      choose to disclose their data, despite the risks.

PMID- 19741611
TI  - Human Genome Sciences trial data wow lupus community.

PMID- 19741612
TI  - Bristol-Myers Squibb swallows last of antibody pioneers.

PMID- 19741613
TI  - Big oil bucks for algae.

PMID- 19741614
TI  - PARP inhibitors blaze a trail in difficult-to-treat cancers.

PMID- 19741619
TI  - China tightens IP protection, but concerns linger.

PMID- 19741609
TI  - Genome sequence and analysis of the Irish potato famine pathogen Phytophthora
      infestans.
AB  - Phytophthora infestans is the most destructive pathogen of potato and a model
      organism for the oomycetes, a distinct lineage of fungus-like eukaryotes that are
      related to organisms such as brown algae and diatoms. As the agent of the Irish
      potato famine in the mid-nineteenth century, P. infestans has had a tremendous
      effect on human history, resulting in famine and population displacement. To this
      day, it affects world agriculture by causing the most destructive disease of
      potato, the fourth largest food crop and a critical alternative to the major
      cereal crops for feeding the world's population. Current annual worldwide potato
      crop losses due to late blight are conservatively estimated at $6.7 billion.
      Management of this devastating pathogen is challenged by its remarkable speed of
      adaptation to control strategies such as genetically resistant cultivars. Here we
      report the sequence of the P. infestans genome, which at approximately 240
      megabases (Mb) is by far the largest and most complex genome sequenced so far in
      the chromalveolates. Its expansion results from a proliferation of repetitive DNA
      accounting for approximately 74% of the genome. Comparison with two other
      Phytophthora genomes showed rapid turnover and extensive expansion of specific
      families of secreted disease effector proteins, including many genes that are
      induced during infection or are predicted to have activities that alter host
      physiology. These fast-evolving effector genes are localized to highly dynamic
      and expanded regions of the P. infestans genome. This probably plays a crucial
      part in the rapid adaptability of the pathogen to host plants and underpins its
      evolutionary potential.

PMID- 19741623
TI  - Trading on hope.

PMID- 19741625
TI  - Receptor-binding specificity of pandemic influenza A (H1N1) 2009 virus determined
      by carbohydrate microarray.

PMID- 19741626
TI  - Preventing the misuse of gene synthesis.

PMID- 19741627
TI  - Commercialized GM crops and yield.

PMID- 19741629
TI  - Commercialized GM crops and yield.

PMID- 19741630
TI  - Commercialized GM crops and yield.

PMID- 19741632
TI  - The neonatal blood-brain barrier is functionally effective, and immaturity does
      not explain differential targeting of AAV9.

PMID- 19741634
TI  - Globetrotting firms: Canada's health biotechnology collaborations with developing
      countries.
AB  - A survey of Canadian biotech firms reveals that their biotech collaborations with
      developing countries are not only significant but also increasingly reciprocal in
      terms of the exchange of financial resources and technological know-how.

PMID- 19741635
TI  - Accelerated patent examination procedures spur Japanese university innovation.
AB  - Two recent events--the issuance of the world's first patent for induced
      pluripotent stem cells and, under a pilot system, the issuance of the fastest
      patent ever granted--signal a watershed in Japanese academia's transition from
      gown to town.

PMID- 19741637
TI  - Faster human genome sequencing.

PMID- 19741638
TI  - Silencing prostate cancer.

PMID- 19741639
TI  - Reshaping pluripotent stem cells.

PMID- 19741640
TI  - Absolute abundance for the masses.

PMID- 19741641
TI  - Combinatorics and next-generation sequencing.

PMID- 19741649
TI  - Interview essentials for executives: beyond the basics.

PMID- 19741651
TI  - Sensory changes after surgical correction of penile curvature.
AB  - In 32 men (mean age 54.94 years, range 25-70 years), thresholds for penile
      thermal and vibratory sensation were recorded before and 3 months after surgery
      using a genital sensory analyser. The following significant changes were found
      postoperatively. The cold threshold decreased in the glans from 27.24 to 25.33
      degrees C (P<0.001) in men older than 60 years, and in the ventral penile shaft
      from 28.54 to 25.46 degrees C (P<0.001) in men aged 35-59 years. The warm
      threshold increased in the glans from 38.31 to 40.61 degrees C (P=0.002) in men
      aged 35-59 years, and from 39.20 to 40.58 degrees C in men older than 60 years
      (P=0.023). The warm threshold also increased in the ventral penile shaft in men
      aged 35-59 years, from 36.62 to 37.82 degrees C (P=0.023). For all three age
      groups combined, the vibratory threshold changed in the glans from 2.33 to 2.93
      mum (P<0.001). It is concluded that penile sensitivity changed significantly
      after surgery for penile curvature treatment, regardless of whether a ventral or
      dorsal surgical approach is used.

PMID- 19741643
TI  - Genome-wide identification of post-translational modulators of transcription
      factor activity in human B cells.
AB  - The ability of a transcription factor (TF) to regulate its targets is modulated
      by a variety of genetic and epigenetic mechanisms, resulting in highly context
      dependent regulatory networks. However, high-throughput methods for the
      identification of proteins that affect TF activity are still largely unavailable.
      Here we introduce an algorithm, modulator inference by network dynamics (MINDy),
      for the genome-wide identification of post-translational modulators of TF
      activity within a specific cellular context. When used to dissect the regulation
      of MYC activity in human B lymphocytes, the approach inferred novel modulators of
      MYC function, which act by distinct mechanisms, including protein turnover,
      transcription complex formation and selective enzyme recruitment. MINDy is
      generally applicable to study the post-translational modulation of mammalian TFs
      in any cellular context. As such it can be used to dissect context-specific
      signaling pathways and combinatorial transcriptional regulation.

PMID- 19741652
TI  - Quantitative EEG in babies at risk for hypoxic ischemic encephalopathy after
      perinatal asphyxia.
AB  - OBJECTIVE: To evaluate an electroencephalography (EEG)-based index, the Cerebral
      Health Index in babies (CHI/b), for identification of neonates with high Sarnat
      scores and abnormal EEG as markers of hypoxic ischemic encephalopathy (HIE) after
      perinatal asphyxia. STUDY DESIGN: This is a retrospective study using 30 min of
      EEG data collected from 20 term neonates with HIE and 20 neurologically normal
      neonates. The HIE diagnosis was made on clinical grounds based on history and
      examination findings. The maximum-modified clinical Sarnat score was used to
      grade HIE severity within 72 h of life. All neonates underwent 2-channel bedside
      EEG monitoring. A trained electroencephalographer blinded to clinical data
      visually classified each EEG as normal, mild or severely abnormal. The CHI/b was
      trained using data from Channel 1 and tested on Channel 2. RESULT: The CHI/b
      distinguished among HIE and controls (P<0.02) and among the three visually
      interpreted EEG categories (P<0.0002). It showed a sensitivity of 82.4% and
      specificity of 100% in detecting high grades of neonatal encephalopathy (Sarnat 2
      and 3), with an area under the receiver operator characteristic (ROC) curve of
      0.912. CHI/b also identified differences between normal vs mildly abnormal
      (P<0.005), mild vs severely abnormal (P<0.01) and normal vs severe (P<0.002) EEG
      groups. An ROC curve analysis showed that the optimal ability of CHI/b to
      discriminate poor outcome was 89.7% (sensitivity: 87.5%; specificity: 82.4%).
      CONCLUSION: The CHI/b identified neonates with high Sarnat scores and abnormal
      EEG. These results support its potential as an objective indicator of
      neurological injury in infants with HIE.

PMID- 19741653
TI  - Factors affecting outcomes in very low birth weight infants treated electively
      with nasal continuous positive airway pressure.
AB  - OBJECTIVE: Although interest in nasal continuous positive airway pressure (nCPAP)
      to avoid intubation is increasing, there is limited data regarding patient
      selection and outcome. We sought to determine the baseline parameters associated
      with failure. STUDY DESIGN: In all, 938 cases of elective nCPAP use were
      extracted from our registry. Two primary end points, Treatment Failure (need for
      intubation) and Bad Outcome (death, need for respiratory support at 40 weeks post
      conceptual age, grade 4 intraventricular hemorrhage or periventricular
      leucomalacia), and 12 potentially predictive baseline parameters were
      prospectively defined and evaluated using logistic regression. RESULT: Intubation
      occurred in 31%, and Bad Outcome occurred in 11%. Besides estimated gestational
      age (EGA), only a few variables were significant predictors in the multivariate
      models: Intubation (PaO(2)/FiO(2)<150 or pH< 7.25) and Bad Outcome (FiO(2), low
      weight for EGA). The relative risk doubled between infants of 34 and 26 weeks EGA
      and increased by about 50% for those meeting the other criteria. CONCLUSION: We
      hope these findings will help those using elective nCPAP to refine their practice
      and those considering its use in establishing reasonable guidelines, as well as
      be useful for designing clinical research.

PMID- 19741654
TI  - Rapid versus standard testing for prenatal HIV screening in a predominantly
      Hispanic population.
AB  - OBJECTIVE: This study aimed to examine the false positive rate of the OraQuick
      rapid human immunodeficiency virus (HIV) test compared with the ELISA test in
      pregnant patients of low socioeconomic status. STUDY DESIGN: Blood samples from
      pregnant patients collected between 10 February 2005 and 1 June 2005 were tested
      with HIV ELISA and OraQuick rapid HIV tests. The positive predictive values of
      both tests were calculated. RESULT: Of 910 patients, 14 (1.5%) patients had a
      positive HIV ELISA test, with only 5 patients confirmed for HIV. The positive
      predictive value for the ELISA test was 35.7% compared with 100% for the OraQuick
      rapid test. CONCLUSION: In a predominantly low socioeconomic Hispanic patient
      population with a 0.5% HIV prevalence, false positive HIV testing is lower for
      the OraQuick rapid HIV test compared with the HIV ELISA test. Implementation of
      the rapid HIV test would mitigate the emotional distress and unnecessary
      intrapartum and neonatal zidovudine treatments associated with false positive HIV
      testing.

PMID- 19741658
TI  - A step too far?

PMID- 19741659
TI  - Data's shameful neglect.
AB  - Research cannot flourish if data are not preserved and made accessible. All
      concerned must act accordingly.

PMID- 19741660
TI  - Overrated ratings.
AB  - Criteria for 'green buildings' need to make energy performance a priority--as do
      universities.

PMID- 19741666
TI  - Journal club. A biologist is gratified to find reconciliation for a conflicted
      receptor.

PMID- 19741672
TI  - Cash crisis could ground NASA rocket.

PMID- 19741673
TI  - How green is your campus?

PMID- 19741674
TI  - Export-control laws worry academics.

PMID- 19741675
TI  - Ethics scrutiny needed for Chinese-European projects.

PMID- 19741676
TI  - Toxicity testing gets a makeover.

PMID- 19741679
TI  - Data sharing: Empty archives.

PMID- 19741680
TI  - Evolution: Mouth to mouth.

PMID- 19741681
TI  - Religious belief and the history of science.

PMID- 19741682
TI  - Evolution pioneers: Lamarck's reputation saved by his zoology.

PMID- 19741683
TI  - Evolution pioneers: celebrating Lamarck at 200, Darwin 215.

PMID- 19741684
TI  - Choking on carbon emissions from Greek academic paperwork.

PMID- 19741685
TI  - Prepublication data sharing.
AB  - Rapid release of prepublication data has served the field of genomics well.
      Attendees at a workshop in Toronto recommend extending the practice to other
      biological data sets.

PMID- 19741686
TI  - Post-publication sharing of data and tools.
AB  - Despite existing guidelines on access to data and bioresources, good practice is
      not widespread. A meeting of mouse researchers in Rome proposes ways to promote a
      culture of sharing.

PMID- 19741690
TI  - Sex determination: Birds do it with a Z gene.

PMID- 19741691
TI  - Nanotechnology: A gentle jackhammer.

PMID- 19741692
TI  - Early Earth: Oxygen for heavy-metal fans.

PMID- 19741694
TI  - Cell biology: Sent by the scent of death.

PMID- 19741695
TI  - Materials chemistry: Catalysts made thinner.

PMID- 19741696
TI  - Developmental biology: Instructions writ in blood.

PMID- 19741697
TI  - Transcribing the genome.

PMID- 19741698
TI  - Defining mechanisms that regulate RNA polymerase II transcription in vivo.
AB  - In the eukaryotic genome, the thousands of genes that encode messenger RNA are
      transcribed by a molecular machine called RNA polymerase II. Analysing the
      distribution and status of RNA polymerase II across a genome has provided crucial
      insights into the long-standing mysteries of transcription and its regulation.
      These studies identify points in the transcription cycle where RNA polymerase II
      accumulates after encountering a rate-limiting step. When coupled with genome
      wide mapping of transcription factors, these approaches identify key regulatory
      steps and factors and, importantly, provide an understanding of the mechanistic
      generalities, as well as the rich diversities, of gene regulation.

PMID- 19741699
TI  - The logic of chromatin architecture and remodelling at promoters.
AB  - The regulation of gene transcription involves a dynamic balance between packaging
      regulatory sequences into chromatin and allowing transcriptional regulators
      access to these sequences. Access is restricted by the nucleosomes, but these can
      be repositioned or ejected by enzymes known as nucleosome remodellers. In
      addition, the DNA sequence can impart stiffness or curvature to the DNA, thereby
      affecting the position of nucleosomes on the DNA, influencing particular promoter
      'architectures'. Recent genome-wide studies in yeast suggest that constitutive
      and regulated genes have architectures that differ in terms of nucleosome
      position, turnover, remodelling requirements and transcriptional noise.

PMID- 19741700
TI  - Genomic views of distant-acting enhancers.
AB  - In contrast to protein-coding sequences, the significance of variation in non
      coding DNA in human disease has been minimally explored. A great number of recent
      genome-wide association studies suggest that non-coding variation is a
      significant risk factor for common disorders, but the mechanisms by which this
      variation contributes to disease remain largely obscure. Distant-acting
      transcriptional enhancers--a major category of functional non-coding DNA--are
      involved in many developmental and disease-relevant processes. Genome-wide
      approaches to their discovery and functional characterization are now available
      and provide a growing knowledge base for the systematic exploration of their role
      in human biology and disease susceptibility.

PMID- 19741701
TI  - Implications of chimaeric non-co-linear transcripts.
AB  - Deep sequencing of 'transcriptomes'--the collection of all RNA transcripts
      produced at a given time--from worms to humans reveals that some transcripts are
      composed of sequence segments that are not co-linear, with pieces of sequence
      coming from distant regions of DNA, even different chromosomes. Some of these
      'chimaeric' transcripts are formed by genetic rearrangements, but others arise
      during post-transcriptional events. The 'trans-splicing' process in lower
      eukaryotes is well understood, but events in higher eukaryotes are not. The
      existence of such chimaeric RNAs has far-reaching implications for the potential
      information content of genomes and the way it is arranged.

PMID- 19741702
TI  - Chromosome crosstalk in three dimensions.
AB  - The genome forms extensive and dynamic physical interactions with itself in the
      form of chromosome loops and bridges, thus exploring the three-dimensional space
      of the nucleus. It is now possible to examine these interactions at the molecular
      level, and we have gained glimpses of their functional implications. Chromosomal
      interactions can contribute to the silencing and activation of genes within the
      three-dimensional context of the nuclear architecture. Technical advances in
      detecting these interactions contribute to our understanding of the functional
      organization of the genome, as well as its adaptive plasticity in response to
      environmental changes during development and disease.

PMID- 19741703
TI  - Molecular networks as sensors and drivers of common human diseases.
AB  - The molecular biology revolution led to an intense focus on the study of
      interactions between DNA, RNA and protein biosynthesis in order to develop a more
      comprehensive understanding of the cell. One consequence of this focus was a
      reduced attention to whole-system physiology, making it difficult to link
      molecular biology to clinical medicine. Equipped with the tools emerging from the
      genomics revolution, we are now in a position to link molecular states to
      physiological ones through the reverse engineering of molecular networks that
      sense DNA and environmental perturbations and, as a result, drive variations in
      physiological states associated with disease.

PMID- 19741704
TI  - The global distribution of pure anorthosite on the Moon.
AB  - It has been thought that the lunar highland crust was formed by the
      crystallization and floatation of plagioclase from a global magma ocean, although
      the actual generation mechanisms are still debated. The composition of the lunar
      highland crust is therefore important for understanding the formation of such a
      magma ocean and the subsequent evolution of the Moon. The Multiband Imager on the
      Selenological and Engineering Explorer (SELENE) has a high spatial resolution of
      optimized spectral coverage, which should allow a clear view of the composition
      of the lunar crust. Here we report the global distribution of rocks of high
      plagioclase abundance (approaching 100 vol.%), using an unambiguous plagioclase
      absorption band recorded by the SELENE Multiband Imager. If the upper crust
      indeed consists of nearly 100 vol.% plagioclase, this is significantly higher
      than previous estimates of 82-92 vol.% (refs 2, 6, 7), providing a valuable
      constraint on models of lunar magma ocean evolution.

PMID- 19741705
TI  - Coherent optical pulse sequencer for quantum applications.
AB  - The bandwidth and versatility of optical devices have revolutionized information
      technology systems and communication networks. Precise and arbitrary control of
      an optical field that preserves optical coherence is an important requisite for
      many proposed photonic technologies. For quantum information applications, a
      device that allows storage and on-demand retrieval of arbitrary quantum states of
      light would form an ideal quantum optical memory. Recently, significant progress
      has been made in implementing atomic quantum memories using electromagnetically
      induced transparency, photon echo spectroscopy, off-resonance Raman spectroscopy
      and other atom-light interaction processes. Single-photon and bright-optical
      field storage with quantum states have both been successfully demonstrated. Here
      we present a coherent optical memory based on photon echoes induced through
      controlled reversible inhomogeneous broadening. Our scheme allows storage of
      multiple pulses of light within a chosen frequency bandwidth, and stored pulses
      can be recalled in arbitrary order with any chosen delay between each recalled
      pulse. Furthermore, pulses can be time-compressed, time-stretched or split into
      multiple smaller pulses and recalled in several pieces at chosen times. Although
      our experimental results are so far limited to classical light pulses, our
      technique should enable the construction of an optical random-access memory for
      time-bin quantum information, and have potential applications in quantum
      information processing.

PMID- 19741706
TI  - Stable single-unit-cell nanosheets of zeolite MFI as active and long-lived
      catalysts.
AB  - Zeolites-microporous crystalline aluminosilicates-are widely used in
      petrochemistry and fine-chemical synthesis because strong acid sites within their
      uniform micropores enable size- and shape-selective catalysis. But the very
      presence of the micropores, with aperture diameters below 1 nm, often goes hand
      in-hand with diffusion limitations that adversely affect catalytic activity. The
      problem can be overcome by reducing the thickness of the zeolite crystals, which
      reduces diffusion path lengths and thus improves molecular diffusion. This has
      been realized by synthesizing zeolite nanocrystals, by exfoliating layered
      zeolites, and by introducing mesopores in the microporous material through
      templating strategies or demetallation processes. But except for the exfoliation,
      none of these strategies has produced 'ultrathin' zeolites with thicknesses below
      5 nm. Here we show that appropriately designed bifunctional surfactants can
      direct the formation of zeolite structures on the mesoporous and microporous
      length scales simultaneously and thus yield MFI (ZSM-5, one of the most important
      catalysts in the petrochemical industry) zeolite nanosheets that are only 2 nm
      thick, which corresponds to the b-axis dimension of a single MFI unit cell. The
      large number of acid sites on the external surface of these zeolites renders them
      highly active for the catalytic conversion of large organic molecules, and the
      reduced crystal thickness facilitates diffusion and thereby dramatically
      suppresses catalyst deactivation through coke deposition during methanol-to
      gasoline conversion. We expect that our synthesis approach could be applied to
      other zeolites to improve their performance in a range of important catalytic
      applications.

PMID- 19741707
TI  - Fluctuations in Precambrian atmospheric oxygenation recorded by chromium
      isotopes.
AB  - Geochemical data suggest that oxygenation of the Earth's atmosphere occurred in
      two broad steps. The first rise in atmospheric oxygen is thought to have occurred
      between approximately 2.45 and 2.2 Gyr ago, leading to a significant increase in
      atmospheric oxygen concentrations and concomitant oxygenation of the shallow
      surface ocean. The second increase in atmospheric oxygen appears to have taken
      place in distinct stages during the late Neoproterozoic era ( approximately 800
      542 Myr ago), ultimately leading to oxygenation of the deep ocean approximately
      580 Myr ago, but details of the evolution of atmospheric oxygenation remain
      uncertain. Here we use chromium (Cr) stable isotopes from banded iron formations
      (BIFs) to track the presence of Cr(VI) in Precambrian oceans, providing a time
      resolved picture of the oxygenation history of the Earth's atmosphere-hydrosphere
      system. The geochemical behaviour of Cr is highly sensitive to the redox state of
      the surface environment because oxidative weathering processes produce the
      oxidized hexavalent [Cr(VI)] form. Oxidation of reduced trivalent [Cr(III)]
      chromium on land is accompanied by an isotopic fractionation, leading to
      enrichment of the mobile hexavalent form in the heavier isotope. Our fractionated
      Cr isotope data indicate the accumulation of Cr(VI) in ocean surface waters
      approximately 2.8 to 2.6 Gyr ago and a likely transient elevation in atmospheric
      and surface ocean oxygenation before the first great rise of oxygen 2.45-2.2 Gyr
      ago (the Great Oxidation Event). In approximately 1.88-Gyr-old BIFs we find that
      Cr isotopes are not fractionated, indicating a decline in atmospheric oxygen. Our
      findings suggest that the Great Oxidation Event did not lead to a unidirectional
      stepwise increase in atmospheric oxygen. In the late Neoproterozoic, we observe
      strong positive fractionations in Cr isotopes (delta(53)Cr up to +4.9 per
      thousand), providing independent support for increased surface oxygenation at
      that time, which may have stimulated rapid evolution of macroscopic multicellular
      life.

PMID- 19741708
TI  - Nucleotides released by apoptotic cells act as a find-me signal to promote
      phagocytic clearance.
AB  - Phagocytic removal of apoptotic cells occurs efficiently in vivo such that even
      in tissues with significant apoptosis, very few apoptotic cells are detectable.
      This is thought to be due to the release of 'find-me' signals by apoptotic cells
      that recruit motile phagocytes such as monocytes, macrophages and dendritic
      cells, leading to the prompt clearance of the dying cells. However, the identity
      and in vivo relevance of such find-me signals are not well understood. Here,
      through several lines of evidence, we identify extracellular nucleotides as a
      critical apoptotic cell find-me signal. We demonstrate the caspase-dependent
      release of ATP and UTP (in equimolar quantities) during the early stages of
      apoptosis by primary thymocytes and cell lines. Purified nucleotides at these
      concentrations were sufficient to induce monocyte recruitment comparable to that
      of apoptotic cell supernatants. Enzymatic removal of ATP and UTP (by apyrase or
      the expression of ectopic CD39) abrogated the ability of apoptotic cell
      supernatants to recruit monocytes in vitro and in vivo. We then identified the
      ATP/UTP receptor P2Y(2) as a critical sensor of nucleotides released by apoptotic
      cells using RNA interference-mediated depletion studies in monocytes, and
      macrophages from P2Y(2)-null mice. The relevance of nucleotides in apoptotic cell
      clearance in vivo was revealed by two approaches. First, in a murine air-pouch
      model, apoptotic cell supernatants induced a threefold greater recruitment of
      monocytes and macrophages than supernatants from healthy cells did; this
      recruitment was abolished by depletion of nucleotides and was significantly
      decreased in P2Y(2)(-/-) (also known as P2ry2(-/-)) mice. Second, clearance of
      apoptotic thymocytes was significantly impaired by either depletion of
      nucleotides or interference with P2Y receptor function (by pharmacological
      inhibition or in P2Y(2)(-/-) mice). These results identify nucleotides as a
      critical find-me cue released by apoptotic cells to promote P2Y(2)-dependent
      recruitment of phagocytes, and provide evidence for a clear relationship between
      a find-me signal and efficient corpse clearance in vivo.

PMID- 19741711
TI  - Abrogation of high-affinity IgE receptor-mediated mast cell activation at the
      effector phase prevents contact hypersensitivity to oxazolone.
AB  - Inflammatory mediators released from mast cells (MCs) through engagement of the
      high-affinity receptor for IgE (FcepsilonRI) have pivotal roles in chemical
      allergen-induced contact hypersensitivity (CHS) reactions, which suggests that
      the blockade of MC activation through FcepsilonRI stimulation may attenuate
      allergic contact dermatitis (CD). To address this possibility, we employed the
      following two approaches: (i) modulation of FcepsilonRI-mediated MC activation by
      introducing mutations in tyrosine residues of the FcepsilonRI beta-chain
      immunoreceptor tyrosine-based activation motif (ITAM) and (ii) blockade of
      FcepsilonRI-mediated MC activation employing a recombinant soluble ecto-domain of
      the human FcepsilonRIalpha-chain (rsFcepsilonRIalpha). In this study, we show
      that optimal MC activation through the FcepsilonRI beta-chain ITAM has essential
      roles in the onset of CHS to oxazolone (Oxa), a well-characterized chemical
      allergen. In addition, we demonstrate that administration of the
      rsFcepsilonRIalpha after sensitization successfully prevents murine CHS to Oxa.
      In a chronic CD model elicited by multiple challenges with low-dose Oxa,
      application of the rsFcepsilonRIalpha during the course of the challenges showed
      suppressive effects on CHS to Oxa. Taken together, our data indicate that
      inhibition of FcepsilonRI-dependent MC activation can suppress allergic CD.

PMID- 19741712
TI  - Valrubicin in a topical formulation treats psoriasis in a xenograft
      transplantation model.
AB  - Valrubicin is a cytostatic drug currently approved by the American Federal Drug
      Administration as a trademarked Valstar sterile solution for the treatment of
      bladder cancer. Valrubicin has shown an excellent therapeutic potential with
      minimal toxicity. This study investigated the effect in vivo of treating
      psoriasis with a daily topical application of valrubicin cream in a psoriasis
      xenograft transplantation model. Psoriasis is characterized by an accelerated
      keratinocyte proliferation, resulting in increased epidermal thickness. We thus
      studied the cytostatic potential of valrubicin on epidermal keratinocytes. In
      vivo, valrubicin treatment resulted in a normalization of epidermal morphology
      and a reduction in epidermal thickness after 12 days. In addition, the dermal
      vessel pattern was reduced and the stratum granulosum was regained. Staining for
      a regenerative proliferation marker showed a decrease in keratinocyte
      proliferation, and scattered epidermal cells showed apoptosis. In vitro,
      valrubicin was shown to localize solely to the cell cytoplasm in cultured
      keratinocytes and to reduce keratinocyte proliferation as well as increase
      apoptosis by activation of caspases 3, 7, and 9. Our results indicated that
      valrubicin successfully treats psoriasis in a xenograft transplantation model,
      suggesting that topical valrubicin may become an upcoming treatment for
      psoriasis.

PMID- 19741713
TI  - Acute acidification of stratum corneum membrane domains using polyhydroxyl acids
      improves lipid processing and inhibits degradation of corneodesmosomes.
AB  - Neutralization of the normally acidic stratum corneum (SC) has deleterious
      consequences for permeability barrier homeostasis and SC integrity/cohesion
      attributable to serine proteases (SPs) activation leading to
      deactivation/degradation of lipid-processing enzymes and corneodesmosomes (CD).
      As an elevated pH compromises SC structure and function, we asked here whether SC
      hyperacidification would improve the structure and function. We lowered the pH of
      mouse SC using two polyhydroxyl acids (PHA), lactobionic acid (LBA), or
      gluconolactone (GL). Applications of the PHA reduced the pH at all levels of SC
      of hairless mouse, with further selective acidification of SC membrane domains,
      as shown by fluorescence lifetime imaging. Hyperacidification improved
      permeability barrier homeostasis, attributable to increased activities of two key
      membrane-localized, ceramide-generating hydrolytic enzymes (beta
      glucocerebrosidase and acidic sphingomyelinase), which correlated with
      accelerated extracellular maturation of SC lamellar membranes. Hyperacidification
      generated "supernormal" SC integrity/cohesion, attributable to an SP-dependent
      decreased degradation of desmoglein-1 (DSG1) and the induction of DSG3 expression
      in lower SC. As SC hyperacidification improves the structure and function, even
      of normal epidermis, these studies lay the groundwork for an assessment of the
      potential utility of SC acidification as a therapeutic strategy for inflammatory
      dermatoses, characterized by abnormalities in barrier function, cohesion, and
      surface pH.

PMID- 19741714
TI  - COP1 contributes to UVB-induced signaling in human keratinocytes.
AB  - UVB irradiation has been shown to trigger a broad range of changes in gene
      expression in human skin; however, factors governing these events are still not
      well understood. In this study, we show that human constitutive photomorphogenic
      protein-1 (huCOP1), an E3 ligase, contributes to the orchestration of UVB
      response of keratinocytes. Accordingly, our data show that (i) huCOP1 protein is
      expressed both in the nucleus and in the cytoplasm of cultured keratinocytes,
      (ii) UVB reduces the levels of the huCOP1 mRNA and protein, and (iii) induces
      changes in the subcellular localization of huCOP1. Finally, we show that gene
      specific silencing of huCOP1 induces the accumulation of the tumor suppressor p53
      protein, which is further increased after UVB irradiation.

PMID- 19741715
TI  - Genetic association of htSNPs across the major histocompatibility complex with
      rheumatoid arthritis in an African-American population.
AB  - Notwithstanding the well-established association of HLA-DRB1 shared epitope
      alleles, interest remains in identifying additional major histocompatibility
      complex (MHC) region variants associated with rheumatoid arthritis (RA). We used
      a panel of 1201 haplotype-tagging single nucleotide polymorphisms (SNPs) designed
      for African Americans to find genetic variants associated with RA in a 3.8-Mb
      region encompassing the MHC. Conditioning on seven covariates, including HLA-DRB1
      risk alleles and population structure, we identified an SNP in HLA-DOA
      (rs9276977) significantly associated with RA; minor allele frequency (MAF) 0.27
      in cases versus 0.21 in controls, odds ratio (+/-95% confidence interval)=2.86
      (1.61, 5.31). Genotyping of rs9276977 in an independent sample of African
      American RA patients and controls did not replicate the association (MAF 0.28 in
      cases versus 0.27 in controls). This study points to the potential association of
      a SNP in the HLA-DOA gene with RA in African Americans, but also underscores the
      importance of replication of findings in larger patient cohorts.

PMID- 19741716
TI  - Association of copy number variation in the FCGR3B gene with risk of autoimmune
      diseases.
AB  - Copy number variation (CNV) in the human genome is an important determinant of
      susceptibility to autoimmune diseases. Many autoimmune diseases share similar
      clinical and pathogenic features. Thus, CNVs of genes involved in immunity may
      serve as shared determinants of multiple autoimmune diseases. Here, we determined
      the association between CNV in the gene encoding FCGR3B with the risk of
      developing autoimmune diseases and whether the observed associations are modified
      by the CNV in CCL3L1 (CC chemokine ligand 3-like 1), a gene encoding a potent
      chemokine. In a cross-sectional study of 774 subjects, we estimated FCGR3B and
      CCL3L1 gene copy number in 146, 158 and 61 subjects with systemic lupus
      erythematosus (SLE), rheumatoid arthritis (RA) and primary Sjogren's syndrome
      (SS), respectively, and 409 healthy controls. The median gene dose of FCGR3B in
      the study population was two. FCGR3B copy number < or >2 was associated with an
      increased risk of SLE and primary SS but not RA. This association was mostly
      evident in subjects who also had two copies of CCL3L1. Thus, our data suggest
      that epistatic interactions between CNV of FCGR3B and CCL3L1, two immune response
      genes, may influence phenotypically related autoimmune diseases.

PMID- 19741717
TI  - Bevacizumab: a new hope?

PMID- 19741718
TI  - Postsurgery corneal asphericity and spherical aberration due to ablation
      efficiency reduction and corneal remodelling in refractive surgeries.
AB  - PURPOSE: To explain the origin of changes in corneal asphericity and induced
      spherical aberration after laser refractive surgery. METHODS: A rigorous model,
      CASIM (corneal ablation simulator), has been developed to model the ablation
      profile design, the shot-by-shot ablation process and the corneal remodelling
      that occurs through healing. The dependence of corneal asphericity, induced
      spherical aberration, and achieved refractive correction on corneal remodelling,
      and the ablation efficiency reduction caused by the angle of incidence of the
      excimer beam on the curved cornea are compared to the clinical outcomes reported
      in the literature. RESULTS: When the exact Munnerlyn formula is used, the CASIM
      modelling and the clinical data exhibit a high degree of correlation. The
      modelling predicts that the postoperative cornea will be oblate, with substantial
      induced spherical aberration. A 6-month postsurgery asphericity is predicted by
      CASIM with a correlation of R2=0.94. The corneal remodelling included in CASIM
      accounts, on the average, for 45 and 69% of the increase in asphericity and
      spherical aberration, respectively, with the remainder due to the ablation
      efficiency. CONCLUSIONS: The modelling shows that clinically observed increases
      in corneal asphericity and induction of spherical aberration can be explained by
      the effects of corneal remodelling due to healing and by the ablation efficiency
      reduction due to laser angle of incidence. The model is capable of predicting
      clinical outcomes for procedures performed with flying spot laser systems and
      could be used to design compensated ablation profiles to improve the clinical
      outcomes for custom as well as conventional laser refractive procedures.

PMID- 19741719
TI  - An unusual fundus phenotype of inner retinal sheen in X-linked retinoschisis.

PMID- 19741721
TI  - Relationship of body mass index with haemodynamic variables and abnormalities in
      young adults.
AB  - We aimed at investigating whether the degree of adiposity is related to
      haemodynamic variables such as systolic blood pressure (SBP), diastolic blood
      pressure (DBP) and resting heart rate (HR), and to haemodynamic abnormalities
      such as hypertension and resting tachycardia. A cross-sectional study was carried
      out among young students in Ebonyi State University, Nigeria. A total of 710
      subjects (350 males and 360 females) aged 20-25 years were recruited for the
      study. Resting blood pressure and HR of subjects were measured and the body mass
      index (BMI) was calculated from height and weight measurements. The observed
      prevalences in this study were as follows: overweight, 20% in males and 26% in
      females; obesity, 8% in males and 6% in females; hypertension, 17% in males and
      14% in females; and resting tachycardia, 22% in males and 24% in females. In both
      genders, BMI showed significant correlations (P<0.001 or P<0.01 or P<0.05) with
      SBP, DBP and HR after controlling for age and physical activity status, and SBP
      indicated the strongest association with BMI. Furthermore, the prevalence of
      hypertension and tachycardia increased with an increase in BMI level, whereas
      overweight/obese subjects indicated significantly higher risk of hypertension
      than did the non-overweight/obese controls. The present findings therefore
      strengthen the previously reported usefulness of BMI in predicting cardiovascular
      risks and add to our understanding of the early development of obesity-related
      cardiovascular abnormalities in young adults and the need to prevent obesity
      early in life and to avoid its unfavourable life-threatening consequences later
      in life.

PMID- 19741723
TI  - Identification of native, immunogenic peptides from Cyclin D1.

PMID- 19741724
TI  - Large but not small copy-number alterations correlate to high-risk genomic
      aberrations and survival in chronic lymphocytic leukemia: a high-resolution
      genomic screening of newly diagnosed patients.

PMID- 19741722
TI  - Proteasome inhibitors in the treatment of multiple myeloma.
AB  - Targeting intracellular protein turnover by inhibiting the ubiquitin-proteasome
      pathway as a strategy for cancer therapy is a new addition to our
      chemotherapeutic armamentarium, and has seen its greatest successes against
      multiple myeloma. The first-in-class proteasome inhibitor, bortezomib, was
      initially approved for treatment of patients in the relapsed/refractory setting
      as a single agent, and was recently shown to induce even greater benefits as part
      of rationally designed combinations that overcome chemoresistance. Modulation of
      proteasome function is also a rational approach to achieve chemosensitization to
      other antimyeloma agents, and bortezomib has now been incorporated into the front
      line setting. Bortezomib-based induction regimens are able to achieve higher
      overall response rates and response qualities than was the case with prior
      standards of care, and unlike these older approaches, maintain efficacy in
      patients with clinically and molecularly defined high-risk disease. Second
      generation proteasome inhibitors with novel properties, such as NPI-0052 and
      carfilzomib, are entering the clinical arena, and showing evidence of antimyeloma
      activity. In this spotlight review, we provide an overview of the current state
      of the art use of bortezomib and other proteasome inhibitors against multiple
      myeloma, and highlight areas for future study that will further optimize our
      ability to benefit patients with this disease.

PMID- 19741725
TI  - A multi-center phase I study of clofarabine, etoposide and cyclophosphamide in
      combination in pediatric patients with refractory or relapsed acute leukemia.
AB  - This Phase I study of clofarabine with etoposide and cyclophosphamide for
      children with relapsed/refractory acute lymphoblastic leukemia (ALL) or acute
      myelogenous leukemia (AML) was conducted to determine the maximum tolerated dose
      (MTD), dose-limiting toxicities and the recommended phase 2 doses (RP2Ds). All
      three drugs were administered for five consecutive days in induction and four
      consecutive days in consolidation, for a maximum of eight cycles. A total of 25
      patients (20 ALL and 5 AML) were enrolled in five cohorts. An MTD was not
      reached. The RP2Ds of clofarabine, cyclophosphamide and etoposide were 40, 440
      and 100 mg/m(2)/day, respectively. Complete remission (CR) was achieved in 10
      patients (ALL: nine; AML: one), and CR without platelet recovery in six patients
      (ALL: two; AML: four) for an overall response rate of 64% (ALL: 55%; AML: 100%).
      Of the 16 responders, 9 patients proceeded to hematopoietic stem cell
      transplantation. In conclusion, the combination of clofarabine, etoposide and
      cyclophosphamide was well tolerated and effective in pediatric patients with
      relapsed/refractory leukemia. Of note, the phase II portion of the trial was
      amended after the occurrence of unexpected hepatotoxicity. The ongoing phase II
      study will evaluate the efficacy and safety of this regimen in ALL patients.

PMID- 19741726
TI  - The therapeutic potential of p53 reactivation by nutlin-3a in ALK+ anaplastic
      large cell lymphoma with wild-type or mutated p53.
AB  - p53 is expressed frequently, but is rarely mutated in anaplastic lymphoma kinase
      (ALK)-positive anaplastic large cell lymphoma (ALCL) tumours. Nutlin-3a is a
      recently developed small molecule that targets Mdm2, a critical negative
      regulator of p53, and disrupts the p53-Mdm2 interaction resulting in p53
      stabilization and activation. We show that nutlin-3a activates p53 in ALK+ ALCL
      cells carrying a wild type (wt) or mutated but partially functional p53 gene
      resulting in p53-dependent cell-cycle arrest and apoptosis. Cell-cycle arrest was
      associated with upregulation of the cyclin-dependent kinase inhibitor p21. Nutlin
      3a-induced apoptotic cell death was accompanied by Bax and Puma upregulation,
      downregulation of Bcl-xl, survivin, and caspase-3 cleavage, and this was reduced
      when p53-dependent transactivation activity was inhibited by pifithrin-alpha, or
      when pifithrin-mu was used to inhibit direct p53 targeting of mitochondria.
      Nutlin-3a sensitized the activation of the extrinsic apoptotic pathway in wt-p53
      ALK+ ALCL cells, in part, through upregulation of DR-5 and downregulation of c
      Flip(S/L), and was synergistic with TRAIL in cell death induction. In addition,
      nutlin-3a treatment enhanced doxorubicin cytotoxicity against ALK+ ALCL cells
      harbouring mt p53, and this was associated with p73 upregulation. These data
      suggest that disruption of the p53-mdm2 interaction by nutlin-3a offers a novel
      therapeutic approach for ALK+ ALCL patients.

PMID- 19741727
TI  - High dose ara-C in the treatment of newly diagnosed acute promyelocytic leukemia:
      long-term results of the German AMLCG.
AB  - The objective of this study for newly diagnosed acute promyelocytic leukemia
      (APL) was to evaluate the efficacy of an intensified double induction
      chemotherapy including high dose ara-C (HD) and all-trans retinoic acid (ATRA)
      followed by consolidation and 3 years maintenance therapy. In contrast to APL
      studies stratifying therapy according to pretreatment white blood cell (WBC)
      count < and > or =10 x 10(9)/l (low/intermediate and high risk according to the
      Sanz score), our patients received uniform therapy. From 1994 to 2005, 142
      patients (age, 16-60 years) were enrolled. In the low/intermediate (n=105) vs
      high (n=37) WBC group, the rates of complete remission were 95.2 vs 83.8%, of
      induction death were 4.8 vs 16.2% (P=0.05) and of molecular remission were 87.5
      vs 91.3% (P=1). Long-term overall survival was 84.4 vs 73.0% (P=0.12), event free
      survival was 78.3 vs 67.3% (P=0.11), relapse free survival was 82.1 vs 80.0%
      (P=0.83) and the cumulative incidence of relapse was 7.4 vs 11.4% (P=0.46). No
      relapse or death occurred after 4.7 years. ATRA and intensified chemotherapy
      including HD ara-C followed by prolonged maintenance therapy reduced the relapse
      risk in high risk patients. Pretreatment WBC count > or =10 x 10(9)/l count was
      no relevant prognostic factor for relapse.

PMID- 19741728
TI  - Adult acute erythroleukemia: an analysis of 91 patients treated at a single
      institution.
AB  - Acute erythroleukemia (AML-M6) is an uncommon subtype of acute myeloid leukemia
      (AML); it is considered to have a poor prognosis. From 1 January 1980 to 21 May
      2008, 91 patients with newly diagnosed AML-M6 were seen at the University of
      Texas-M.D. Anderson Cancer Center (UT-MDACC). Forty-five patients (50%) had a
      history of myelodysplatic syndrome (MDS), compared with 41% in our control group
      (patients with other AML subtypes) (P=0.08). Poor-risk cytogenetics were more
      common in patients with AML-M6 (61% versus 38%, P=0.001). Complete remission
      rates were 62% for patients with AML-M6, comparing with 58% for the control group
      (P=0.35). Median disease free survival (DFS) for patients with AML-M6 was 32
      weeks, versus 49 weeks for the control group (P=0.05). Median overall survival
      (OS) of patients with AML-M6 was 36 weeks, compared with 43 weeks for the control
      group (P=0.60). On multivariate analysis for DFS and OS, AML-M6 was not an
      independent risk factor. AML-M6 is commonly associated with a previous diagnosis
      of MDS and poor-risk karyotype. The diagnosis of AML-M6 does not impart by itself
      a worse prognosis, and treatment decisions on this disease should be guided by
      well known AML prognostic factors.

PMID- 19741730
TI  - PDGF-B gene therapy accelerates bone engineering and oral implant
      osseointegration.
AB  - Platelet-derived growth factor-BB (PDGF-BB) stimulates repair of healing-impaired
      chronic wounds such as diabetic ulcers and periodontal lesions. However,
      limitations in predictability of tissue regeneration occur due, in part, to
      transient growth factor bioavailability in vivo. Here, we report that gene
      delivery of PDGF-B stimulates repair of oral implant extraction socket defects.
      Alveolar ridge defects were created in rats and were treated at the time of
      titanium implant installation with a collagen matrix containing an adenoviral
      (Ad) vector encoding PDGF-B (5.5 x 10(8) or 5.5 x 10(9) pfu ml(-1)), Ad encoding
      luciferase (Ad-Luc; 5.5 x 10(9) pfu ml(-1); control) or recombinant human PDGF-BB
      protein (rhPDGF-BB, 0.3 mg ml(-1)). Bone repair and osseointegration were
      measured through backscattered scanning electron microscopy, histomorphometry,
      micro-computed tomography and biomechanical assessments. Furthermore, a panel of
      local and systemic safety assessments was performed. Results indicated that bone
      repair was accelerated by Ad-PDGF-B and rhPDGF-BB delivery compared with Ad-Luc,
      with the high dose of Ad-PDGF-B more effective than the low dose. No significant
      dissemination of the vector construct or alteration of systemic parameters was
      noted. In summary, gene delivery of Ad-PDGF-B shows regenerative and safety
      capabilities for bone tissue engineering and osseointegration in alveolar bone
      defects comparable with rhPDGF-BB protein delivery in vivo.

PMID- 19741729
TI  - The use of novel agents in the treatment of relapsed and refractory multiple
      myeloma.
AB  - Although outcomes for patients with multiple myeloma (MM) have improved over the
      past decade, the disease remains incurable and even patients who respond well to
      induction therapy ultimately relapse and require additional treatment.
      Conventional chemotherapy and high-dose therapy with stem cell transplantation
      (SCT) have historically been utilized in the management of relapsed MM, but in
      recent years the immunomodulatory drugs (IMiDs) thalidomide and lenalidomide, as
      well as the proteasome inhibitor bortezomib, have assumed a primary role in this
      setting. This review focuses on the role of thalidomide, lenalidomide and
      bortezomib in relapsed and refractory MM, with additional discussion dedicated to
      emerging drugs in relapsed MM that may prove beneficial to patients with this
      disease.

PMID- 19741731
TI  - Therapeutic potential of genetically modified adult stem cells for osteopenia.
AB  - Adult stem cells have therapeutic potential because of their intrinsic capacity
      for self-renewal, especially for bone regeneration. The present study shows the
      utility of ex vivo modified mesenchymal stem cells (MSC) to enhance bone density
      in an immunocompetent mouse model of osteopenia. MSC were transduced ex vivo with
      a recombinant adeno-associated virus 2 (rAAV2) expressing bone morphogenetic
      protein 2 (BMP2) under the transcriptional control of collagen type-1alpha
      promoter. To enrich bone homing in vivo, we further modified the cells to
      transiently express the mouse alpha4 integrin. The modified MSC were systemically
      administered to ovariectomized, female C57BL/6 mice. Effects of the therapy were
      determined by dual-energy X-ray absorptiometry, 3D micro-CT, histology and
      immunohistochemistry for up to 6 months. Results indicated that mice transplanted
      with MSC expressing BMP2 showed significant increase in bone mineral density and
      bone mineral content (P < 0.001) with relatively better proliferative
      capabilities of bone marrow stromal cells and higher osteocompetent pool of cells
      compared to control animals. Micro-CT analysis of femora and other bone
      histomorphometric analyses indicated more trabecular bone following MSC-BMP2
      therapy. Results obtained by transplanting genetically modified MSC from green
      fluorescent protein transgenic mouse suggested that production of BMP2 from
      transplanted MSC also influenced the mobilization of endogenous progenitors for
      new bone formation.

PMID- 19741732
TI  - High efficiency non-viral transfection of retinal and iris pigment epithelial
      cells with pigment epithelium-derived factor.
AB  - Transplantation of pigment epithelial cells in patients with age-related macular
      degeneration and Parkinson's disease has the potential to improve functional
      rehabilitation. Genetic modification of cells before transplantation may allow
      the delivery of neuroprotective factors to achieve functional improvement. As
      transplantation of cells modified using viral vectors is complicated by the
      possible dissemination of viral particles and severe immune reactions, we have
      explored non-viral methods to insert genetic material in pigment epithelial
      cells. Using lipofection or nucleofection ARPE-19 cells, freshly isolated and
      primary retinal and iris pigment epithelial (IPE) cells were transfected with
      plasmids encoding green fluorescent protein (GFP) and with three plasmids
      encoding recombinant pigment epithelium-derived factor (PEDF) and GFP.
      Transfection efficiency was evaluated by fluorescence microscopy and stability of
      protein expression by immunoblotting. Pigment epithelial cells were successfully
      transfected with plasmid encoding GFP. Expression of GFP in ARPE-19 was
      transient, but was observed for up to 1 year in IPE cells. Analysis of pigment
      epithelial cells transfected with PEDF plasmids revealed that PEDF fusion
      proteins were successfully expressed and functionally active. In conclusion,
      efficient transfer of genetic information in pigment epithelial cells can be
      achieved using non-viral transfection protocols.

PMID- 19741734
TI  - Suicide gene therapy on spontaneous canine melanoma: correlations between in vivo
      tumors and their derived multicell spheroids in vitro.
AB  - To validate the use of multicellular spheroids to predict the efficacy of herpes
      simplex thymidine kinase/ganciclovir (HSVtk/GCV) suicide gene therapy in the
      respective in vivo tumors, we established and characterized 15 melanoma-derived
      cell lines from surgically excised melanoma tumors. Three HSVtk-lipofected cell
      lines were not sensitive to GCV in any culture configuration, other five
      displayed similar sensitivity as monolayers or spheroids, and only one resulted
      more sensitive when grown as spheroids. Other six cell lines manifested a
      relative multicellular resistance (MCR) phenotype growing as spheroids, compared
      with the same cells growing as monolayers. The reverse correlation between the
      MCR and the monolayers survival to HSVtk/GCV suggests that one of the main causes
      of MCR would be the rapid cell repopulation after suicide gene treatment. The
      high correlation of MCR with the spheroids radial growth and with the mitotic
      index of the respective originary tumors supported this re-growth involvement. A
      remarkable finding was the high correlation in HSVtk/GCV sensitivity between in
      vivo tumor and the corresponding derived cell lines growing as spheroids (R(2) =
      0.85). This strongly encourages the implementation of spheroids as highly
      realistic experimental model for optimizing and predicting the in vivo response
      of the respective tumors to therapeutic strategies.

PMID- 19741733
TI  - Foamy combinatorial anti-HIV vectors with MGMTP140K potently inhibit HIV-1 and
      SHIV replication and mediate selection in vivo.
AB  - Highly active antiretroviral therapy has greatly reduced the morbidity and
      mortality from human immunodeficiency virus (HIV) infection, but AIDS continues
      to be a serious health problem worldwide. Despite enormous efforts to develop a
      vaccine, there is still no cure, and alternative approaches including gene
      therapy should be explored. In this study we developed and compared combinatorial
      foamy virus (FV) anti-HIV vectors that also express a mutant methylguanine
      methyltransferase (MGMTP140K) transgene to increase the percentage of gene
      modified cells after transplantation. These FV vectors inhibit replication of HIV
      1 and also the simian immunodeficiency virus/HIV-1 (SHIV) chimera that can be
      used in monkey AIDS gene therapy studies. We identified a combinatorial FV vector
      that expresses 3 anti-HIV transgenes and inhibits viral replication by over 4
      logs in a viral challenge assay. This FV anti-HIV vector expresses an HIV fusion
      inhibitor and two short hairpin RNAs (shRNAs) targeted to HIV-1 tat and rev, and
      can be produced at high titer (3.8 x 10(7) transducing units ml(-1)) using
      improved helper plasmids suitable for clinical use. Using a competitive
      repopulation assay, we show that human CD34(+) cells transduced with this
      combinatorial FV vector efficiently engraft in a mouse xenotransplantation model,
      and that the percentage of transduced repopulating cells can be increased after
      transplantation.

PMID- 19741735
TI  - The complete genome sequence of the algal symbiont Dinoroseobacter shibae: a
      hitchhiker's guide to life in the sea.
AB  - Dinoroseobacter shibae DFL12(T), a member of the globally important marine
      Roseobacter clade, comprises symbionts of cosmopolitan marine microalgae,
      including toxic dinoflagellates. Its annotated 4 417 868 bp genome sequence
      revealed a possible advantage of this symbiosis for the algal host. D. shibae
      DFL12(T) is able to synthesize the vitamins B(1) and B(12) for which its host is
      auxotrophic. Two pathways for the de novo synthesis of vitamin B(12) are present,
      one requiring oxygen and the other an oxygen-independent pathway. The de novo
      synthesis of vitamin B(12) was confirmed to be functional, and D. shibae DFL12(T)
      was shown to provide the growth-limiting vitamins B(1) and B(12) to its
      dinoflagellate host. The Roseobacter clade has been considered to comprise
      obligate aerobic bacteria. However, D. shibae DFL12(T) is able to grow
      anaerobically using the alternative electron acceptors nitrate and
      dimethylsulfoxide; it has the arginine deiminase survival fermentation pathway
      and a complex oxygen-dependent Fnr (fumarate and nitrate reduction) regulon. Many
      of these traits are shared with other members of the Roseobacter clade. D. shibae
      DFL12(T) has five plasmids, showing examples for vertical recruitment of
      chromosomal genes (thiC) and horizontal gene transfer (cox genes, gene cluster of
      47 kb) possibly by conjugation (vir gene cluster). The long-range (80%) synteny
      between two sister plasmids provides insights into the emergence of novel
      plasmids. D. shibae DFL12(T) shows the most complex viral defense system of all
      Rhodobacterales sequenced to date.

PMID- 19741737
TI  - Encryption of pictures and shapes by random grids.
AB  - A low-cost and simple technique for encryption of two-dimensional patterns and
      shapes is suggested and demonstrated. The method is based on the superposition of
      random grids.

PMID- 19741736
TI  - Horizontal transfer of the nitrogen fixation gene cluster in the cyanobacterium
      Microcoleus chthonoplastes.
AB  - The filamentous, non-heterocystous cyanobacterium Microcoleus chthonoplastes is a
      cosmopolitan organism, known to build microbial mats in a variety of different
      environments. Although most of these cyanobacterial mats are known for their
      capacity to fix dinitrogen, M. chthonoplastes has not been assigned as a
      diazotrophic organism. None of the strains that were correctly identified as M.
      chthonoplastes has been shown to fix dinitrogen and it has repeatedly been
      reported that these organisms lacked the cyanobacterial nifH, the structural gene
      for dinitrogenase reductase. In this study, we show that a complete nif-gene
      cluster is present in the genome of M. chthonoplastes PCC 7420 and that the three
      structural nitrogenase genes, nifHDK, are present in a collection of axenic
      strains of M. chthonoplastes from distant locations. Phylogenetic analysis of
      nifHDK revealed that they cluster with the Deltaproteobacteria and that they are
      closely related to Desulfovibrio. The nif operon is flanked by typical
      cyanobacterial genes, suggesting that it is an integral part of the M.
      chthonoplastes genome. In this study, we provide evidence that the nif operon of
      M. chthonoplastes is acquired through horizontal gene transfer. Moreover, the
      presence of the same nif-cluster in M. chthonoplastes isolates derived from
      various sites around the world suggests that this horizontal gene transfer event
      must have occurred early in the evolution of M. chthonoplastes. We have been
      unable to express nitrogenase in cultures of M. chthonoplastes, but we show that
      these genes were expressed under natural conditions in the field.

PMID- 19741738
TI  - First and second moments of an optical wave propagating in an absorptive random
      medium.
AB  - By using the path-integral technique, the first and second moments of the
      propagator in an absorptive random medium are evaluated. The effects of random
      fluctuations of absorption are taken into account. In this evaluation, the
      imaginary part of the dielectric permittivity is supposed to fluctuate
      synchronously with the real part according to the Kramers-Kronig relations. Some
      physical insight is discussed.

PMID- 19741739
TI  - Sine-cosine cascade correlator with real-valued filters.
AB  - A novel sine-filter-cosine cascade is proposed that is realizable for either
      coherent or spatially incoherent illumination. Computer simulation is used to
      demonstrate effectively matched filter performance and elimination of deleterious
      background bias.

PMID- 19741740
TI  - Simultaneous acquisition of pure rotational and vibrational nitrogen spectra
      using three-laser coherent anti-Stokes Raman spectroscopy.
AB  - Three-laser coherent anti-Stokes Raman scattering (CARS) was used to acquire
      simultaneously pure rotational and vibrational spectra from the nitrogen
      molecule. This technique has the potential for accurate temperature measurements
      over a wider temperature range than either vibrational or pure rotational CARS
      alone. Third-order susceptibilities for three-laser CARS are derived, and
      polarization effects are discussed.

PMID- 19741741
TI  - Absorption spectroscopy at the limit: detection of a single atom.
AB  - We investigate the sensitivity limit of absorption spectroscopy. An experiment is
      described in which the decrease in transmitted light intensity that is due to
      absorption by a single, electromagnetically confined atomic ion is observed.

PMID- 19741742
TI  - Continuous-wave laser oscillation in a Nd:YAG sphere.
AB  - I report the observation of continuous-wave laser oscillation in a Nd:YAG sphere.
      The spherical laser is excited by a dye laser that is focused to pump selectively
      certain regions of the sphere. With careful mode matching, single-frequency
      oscillation is obtained. The observed emission patterns agree well with the modes
      predicted by a classical treatment of a spherically symmetric resonator. These
      modes are described by products of spherical harmonics and Bessel functions, in
      contrast to the standard Gaussian-beam modes of a linear cavity.

PMID- 19741743
TI  - Generation of 33-fsec pulses at 1.32 microm through a high-order soliton effect
      in a single-mode optical fiber.
AB  - Pulse shortening by a factor of 2700x at 1.32 microm has been realized by means
      of a two-stage pulse compression. In the first stage, 90-psec pulses from a cw
      mode-locked Nd:YAG laser were compressed to ~1.5 psec by using a standard fiber
      grating-pair configuration. Subsequent propagation of these pulses through ~20 m
      of single-mode optical fiber with a minimum dispersion at 1.27 microm led to a
      final pulse width of 33 fsec. This represents the shortest reported pulse
      generated at 1.32 microm by using the technique described above as well as the
      largest overall compression factor using optical fibers yet reported.

PMID- 19741744
TI  - Generation of programmable, picosecond-resolution shaped laser pulses by fiber
      grating pulse compression.
AB  - We demonstrate that fiber-optic compression can be sufficiently well
      characterized to permit generation of an arbitrarily shaped, 1-psec-resolution
      laser pulse from a predistorted, much longer pulse. Coupled with our previously
      demonstrated capability to generate an arbitrary shape with 10-psec resolution
      and software control, this technique provides significant advantages over
      conventional mode-locked, cavity-dumped, synchronously pumped laser systems.

PMID- 19741745
TI  - Prism-pair dispersive delay lines in optical pulse compression.
AB  - We have compressed the output of a synchronously pumped cavity-dumped dye laser
      with a fiber-prism pulse compressor. The prism pair consisted of two dense flint
      glass prisms, which were used at a grazing exit angle to increase the dispersive
      power. We present the results of several experiments in which we have
      demonstrated 85% throughput, high compression ratios, and compressed pulses as
      short as 50 fsec.

PMID- 19741746
TI  - Effect of stimulated Raman scattering on pulse-compression characteristics.
AB  - The effect of stimulated Raman scattering on pulse-compression characteristics
      has been studied experimentally and theoretically. When an optical pulse is
      compressed by an optical fiber and a grating pair, the generation of stimulated
      Raman scattering becomes important. When stimulated Raman scattering occurs, the
      compressed pulse width changes asymmetrically with respect to the magnitude of
      the anomalous dispersion created by the grating pair. The compressed pulse has
      much residual energy in its wings, and it does not have a smooth envelope for
      large anomalous dispersion.

PMID- 19741747
TI  - Ultrashort pulses from the soliton laser.
AB  - We report the production of 50-fsec FWHM pulses directly from the soliton laser
      and 19-fsec pulses with compression in an external fiber. The 19-fsec FWHM
      corresponds to just under four optical cycles at the laser wavelength of 1.5
      microm. We argue that these limits are set by dispersion properties of the
      control and compression fibers.

PMID- 19741748
TI  - Stimulated Brillouin scattering parasitics in large optical windows.
AB  - The growth of optical radiation, scattered transverse to the pump axis by
      stimulated Brillouin scattering (SBS) in optical windows, is considered. Basic
      equations are presented, and an analytic expression that determines the parasitic
      buildup time is derived for a transverse SBS geometry. Losses suffered by the
      scattered optical radiation are included in a bulk-loss term. Calculations are
      performed for fused-silica windows and compared with a numerical model. This
      parasitic process may affect the design of laser systems that will generate
      multinanosecond, multikilojoule, narrow-band pulses in the ultraviolet region.

PMID- 19741749
TI  - Optical nonlinearities of glasses doped with semiconductor microcrystallites.
AB  - The origin of optical nonlinearities of glasses doped with CdS(x)Se(1-x)
      microcrystallites is studied both experimentally and theoretically. At room
      temperature a large shift ( congruent with50 meV) of the absorption spectrum to
      higher energies is observed in a CdS(x)Se(1-x) glass with increased light
      intensity. This blue shift is analyzed by using a semiconductor plasma theory.
      Experimental and theoretical results suggest that band filling is the dominant
      mechanism for the observed nonlinearity. An independent measurement for the
      intensity-dependent dispersive changes is presented.

PMID- 19741750
TI  - Temporal smoothing of multimode dye-laser pulses.
AB  - Pulses from a broadband dye laser operating in many modes have been temporally
      smoothed by passing them through a strongly saturated dye amplifier in the
      presence of a strong, nonsaturable absorber. The standard nonlinear coupled
      partial differential equations based on the rate-equation approximation have been
      used to model the amplifier. Both analytic and numerical solutions for the
      equations show that under attainable conditions the intensity of the amplified
      pulse follows the temporal shape of the pump pulse.

PMID- 19741751
TI  - Optical nonlinearities in a lyotropic liquid crystal.
AB  - The existence of an optical nonlinearity in a lyotropic liquid crystal has been
      demonstrated in an optical waveguide. A large hysteresis, of origin to be
      clarified, is found in the optical response in all mesophases of potassium
      capryllate.

PMID- 19741752
TI  - Chaos in a good-cavity single-mode dye laser due to turbulent dye flow.
AB  - Experimental results are presented that demonstrate that the light intensity of a
      good-cavity single-mode standing-wave dye laser can exhibit chaotic behavior. The
      governing attractor is of dimensionality 6.5 and entropy 50 kbits/sec. An
      examination of the pump-laser beam before and after its interaction with the dye
      indicates that the chaos is probably due to the turbulent flow of dye within the
      dye cell. This interpretation is confirmed by the absence of chaos in two similar
      dye lasers that use a dye jet rather than a dye cell.

PMID- 19741753
TI  - Dimensioning an optical-fiber spread-spectrum multiple-access communication
      system.
AB  - We examine the dimensioning of an optical-fiber-based spread-spectrum multiple
      access communication system that utilizes the inherently broad spectrum of many
      types of semiconductor lasers and LED's as the spreading function.

PMID- 19741754
TI  - Approximate formulas for the microbending loss in single-mode fibers.
AB  - Some approximate formulas for calculating the microbending loss for single-mode
      fibers are given. The formulas are rather simple, yield good approximate values,
      and hence can be used to evaluate the microbending loss in fiber design.

PMID- 19741755
TI  - Effects of cores in fused tapered single-mode fiber couplers.
AB  - Fused tapered single-mode fiber couplers are analyzed in detail by the simple
      effective-index method. It is found that the core parameters of the coupler,
      i.e., the core-cladding radius ratio, the core-cladding profile height, and the
      core separation, can have significant effects on the coupler characteristics. In
      practice, neglect of the cores as in many previous studies may lead to
      intolerable errors.

PMID- 19741756
TI  - Intensity noise characteristics of lasers in fiber-optic gyroscopes.
AB  - We report the first theoretical analysis and experimental results to our
      knowledge of the intensity noise of lasers due to signal-wave feedback in fiber
      optic gyroscopes. It has been demonstrated that signal-wave feedback would cause
      a large amount of intensity noise in lasers and would thus limit the system
      performance. The relation of the intensity noise to various factors in the
      gyroscope has been clarified, and measures to reduce the noise are presented.

PMID- 19741757
TI  - Fiber-optic evanescent-wave methane-gas sensor using optical absorption for the
      3.392-microm line of a He-Ne laser.
AB  - Gas sensing using evanescent waves of optical fibers is investigated. Methane gas
      is detected by means of its strong optical absorption of the 3.392-microm line of
      a He-Ne laser. A single fiber is used as both a sensor and an optical
      transmission line. The sensor has a small diameter, ranging from 1.8 to 7microm,
      made by heating and expanding a part of a step-index silica fiber. An evanescent
      wave of 5 to 40% of the total propagating power is generated outside the fiber.
      When a sensor fiber of 1.8-microm diameter and 10-mm length is used, the minimum
      detectable concentration of methane is less than the lowest explosive limit of
      5%.

PMID- 19741758
TI  - Passive stabilization of a fiber-optic nonlinear sensor by using a sampling
      scheme.
AB  - A new passive stabilization scheme using a synchronous sampling technique has
      been demonstrated for nonlinear fiber interferometric sensors. Passive
      stabilization is achieved by signal normalization derived from multiple time
      samples of a single output.

PMID- 19741759
TI  - Strip-loaded waveguide using an underlay.
AB  - We describe how an ion-exchange waveguide was used as a strip-loading region for
      a planar polymer waveguide. The loading strip forms an underlay that is well
      preserved in the substrate. Some branching-channel waveguides were formed by this
      method, and wall losses were measured. The result shows that the wall losses
      decrease as a result of strip loading.

PMID- 19741760
TI  - Direct measurement of effective indices of guided modes in LiNbO(3) waveguides
      using the Cerenkov second harmonic.
AB  - Second-harmonic generation in the form of Cerenkov radiation has been used to
      make direct, contact-free measurements of the effective indices of guided modes
      in LiNbO(3) channel waveguides. X-cut substrates were used, and channels oriented
      along the y axis were formed by either proton exchange or titanium indiffusion.
      For end-fire TE excitation, the Cerenkov harmonic radiates forward at a shallow
      angle into the substrate, leaves the output facet of the substrate, and appears
      as bright bands in the far field. These bands are seen to form a one-to-one
      correspondence with the m lines that are due to guided modes when a prism coupler
      is simultaneously clamped to the sample surface. The effective indices of the
      guided modes can be obtained by a simple calculation that involves only the
      substrate index and the angle at which the Cerenkov harmonic is radiated into the
      substrate. This technique permits effective index measurements of cladded
      waveguides where prism coupler measurements cannot be made. Examples of the
      technique in which index oil is used as a guide overlayer are given.

PMID- 19741761
TI  - Architectures for optoelectronic analogs of self-organizing neural networks.
AB  - Architectures for partitioning optoelectronic analogs of neural nets into input
      output and internal groups to form a multilayered net capable of self
      organization, self-programming, and learning are described. The architectures and
      implementation ideas given describe a class of optoelectronic neural net modules
      that, when interfaced to a conventional computer controller, can impart to it
      artificial intelligence attributes.

PMID- 19741763
TI  - Nondestructive depth profiling of ZnS and MgO films by spectroscopic
      ellipsometry.
AB  - Spectroscopic ellipsometric (SE) measurements followed by linear-regression
      analysis of the SE data obtained on ZnS and MgO films on vitreous silica
      substrates reveal the distribution of voids (or low-density regions) in these
      transparent thin films.

PMID- 19741764
TI  - Photorefractive acoustoelectro-optic correlator.
AB  - An optical correlator based on acoustoelectro-optic interaction is proposed. The
      device is experimentally demonstrated with a LiNbO(3) crystal in which acoustic
      waves are launched by a piezoelectric transducer and electric fields are
      established through the photorefractive effect.

PMID- 19741762
TI  - Ideal nonfocusing concentrator with fin absorbers in dielectric rhombuses.
AB  - Two ideal concentrators with fin absorbers in dielectric rhombuses are described.
      Expressions for the design, height, and mirror length are derived. The devices
      have a concentration factor (n/sin ?(M)) that is clearly higher than the
      traditional air-filled ideal concentrators. They do not require more mirrors or
      space and, when such easily available dielectrics as glass and water are used,
      offer useful configurations for purposes such as the collection of solar energy.

PMID- 19741765
TI  - Cascaded optical isolator configuration having high-isolation characteristics
      over a wide temperature and wavelength range.
AB  - A new configuration of a cascaded optical isolator with high isolation over a
      wide range of temperature and wavelength is proposed. The configuration consists
      of two unit isolators, each of which is optimized for a different temperature and
      wavelength.

PMID- 19741766
TI  - Quadrupole mode in the extinction and elastic-scattering spectra of gold
      microstructures.
AB  - The quadrupole mode and the retardation-broadened, wavelength-shifted dipole mode
      have been observed in the extinction and elastic-scattering spectra of two
      dimensional arrays of Au microstructures immersed in air, water, and toluene. The
      electron-beam lithographically produced Au microstructures, resembling
      hemispheres with radius ~100 nm, were arranged in a square lattice with a center
      to-center separation of 500 nm and situated on a 5-nm-thick layer of Cr coated on
      an optically flat quartz substrate.

PMID- 19741767
TI  - Ultraviolet optogalvanic laser spectroscopy of iron for reference wavelengths.
AB  - We present a preliminary study of a UV optogalvanic spectrum obtained by using a
      see-through iron hollow cathode and a tunable pulsed laser in the 240-260-nm
      range. The hollow cathode used and described is a homemade device that can be run
      in static- or dynamic-flow gas regimes. Spectra have been recorded with argon and
      neon buffer gases, and many classified Fe I lines have been identified. The
      accuracy of the measured wave numbers is limited at present to 0.05 cm(-1) by the
      spectral width of the UV laser. This iron optogalvanic spectrum is proposed for
      reference-wavelength calibration in UV laser spectroscopy, and an application to
      the study of Ba(+) Rydberg levels is reported. Possibilities for future
      developments of such a device are analyzed.

PMID- 19741768
TI  - Infrared radio-frequency double resonance of (13)CH(3)OH.
AB  - Infrared radio-frequency double-resonance spectroscopy has been carried out for
      (13)CH(3)OH. Four K-type doublet transitions have been observed below 1 GHz,
      using the 9P(10) and 9P(12) CO(2) laser lines. The results confirm previously
      proposed assignments of infrared absorption transitions and far-infrared laser
      emission lines observed in this molecule. Measurements of the A-state splittings
      have permitted the determination of the asymmetry splitting parameters S(O)(K)
      and S(CO)(K) for (n, K) = (0, 4) and (1, 3).

PMID- 19741769
TI  - (F(2)(+))(H) Color-center laser operation in NaCl:OH with simultaneous 1.06- and
      0.53-microm pumping.
AB  - We have operated an (F(2)(+))(H) color-center laser in NaCl:OH using a 1.06
      microm pump laser with a collinear auxiliary beam at 0.53 microm. The auxiliary
      beam is produced by frequency doubling a small fraction of the pump beam instead
      of using an arc lamp, as was previously reported. With a grating tuner, the laser
      tuned from 1.47 to 1 .8 7 microm and produced up to 760 mW of output power. In
      single-frequency operation, powers up to 460 mW with a linewidth <2 MHz were
      achievable. The laser also produced 480 mW of power in cw mode-locked operation
      with transform-limited pulses as short as 5 psec.

PMID- 19741770
TI  - Enhancement of ultrafast supercontinuum generation in water by the addition of
      Zn(2+) and K(+) cations.
AB  - Nonlinear-optical properties of various salts and water solutions were measured
      using an 8-psec laser pulse at 530 nm. It was found that the optical Kerr effect
      and supercontinuum signals were several times larger in saline water than in pure
      water. The optical Kerr effect signals from saturated aqueous solutions of
      ZnCl(2) were about 35 times greater, and the self-phase-modulation signals from
      saturated aqueous solutions of K(2)ZnCl(4) were about 10 times greater.

PMID- 19741771
TI  - Tunable subpicosecond infrared pulse generation to 4 microm.
AB  - High-power, subpicosecond infrared pulses have been generated over the wavelength
      region of 1.7-4.0 microm. The technique uses difference-frequency generation in a
      LiNbO(3) crystal. The subpicosecond output of an amplified colliding-pulse mode
      locked (CPM) ring dye laser provides the two frequencies, one being the CPM
      fundamental, the other a portion of the subpicosecond continuum generated in an
      ethanol cell. Pulse width, power, and spectral characteristics are discussed.

PMID- 19741772
TI  - Compression of optical pulses to six femtoseconds by using cubic phase
      compensation.
AB  - We demonstrate that a combination of prisms and diffraction gratings can provide
      not only quadratic but also cubic phase compensation of ultrashort optical
      pulses. We obtain compressed pulses as short as 6 fsec.

PMID- 19741773
TI  - Effect of pump-laser linewidth on noise in single-pulse coherent anti-Stokes
      Raman spectroscopy temperature measurements.
AB  - When N(2) is used as the probe molecule in a stable premixed propane-air flame
      near 2100 K, the standard deviation in single-pulse coherent anti-Stokes Raman
      spectroscopy (CARS) temperature measurements is shown to decrease by 20% as the
      pump-laser linewidth increases from </=0.02 to about 0.7 cm(-1). This effect is
      shown to be independent of the signal level at the detector array over the range
      considered. An instrument function that is useful in CARS convolution
      calculations is also presented.

PMID- 19741774
TI  - Optical high-order subharmonic excitation of free cyclotron electrons.
AB  - Homogeneous laser radiation in the visible or infrared range can excite high
      order subharmonics at the cyclotron frequency of free electrons in the millimeter
      or microwave range. This may provide coherent links between lasers and rf or
      microwave frequency standards. In order to divide the frequency of a CO(2) laser
      (lambda approximately 10 microm) by a factor of 100 down to lambda approximately
      1 mm in one step, a cw laser power as low as 10(-6) W is sufficient.

PMID- 19741775
TI  - Light propagation in a two-component nonlinear composite medium.
AB  - The propagation of intense light through a two-component nonlinear heterogeneous
      medium is considered by treating the medium as a composite medium. Introduction
      of dispersion and Kerr-type nonlinear terms leads to a nonlinear Schrodinger-type
      scattering equation. The effect of nonlinear scattering loss on soliton
      propagation is studied numerically. The propagation of two oppositely traveling
      waves is also discussed.

PMID- 19741776
TI  - Measurement of Raman gain of the S(8) transition of N(2).
AB  - The ratio of the rotational Raman gain coefficients g of N(2) [S(8), 0.91 amagat]
      and H(2) [S(1), 0.73 amagat] was determined at 295 K by measuring the 5%
      conversion threshold for each in the same focused configuration, using a
      circularly polarized 1054-nm laser. After correcting for dispersion, the optical
      Stark effect, transient effects, laser-wing Stokes seed injection, and mode-beat
      intensity modulation, we obtained g(N(2))/g(H(2)) = (8.0 +/- 1.2) x 10(-3), so
      that g(N(2)) = 4.0 +/- 0.8 cm/TW.

PMID- 19741777
TI  - Analysis of mutually incoherent beam coupling in BaTiO(3).
AB  - When two mutually incoherent light beams are used as simultaneous inputs to a
      crystal of BaTiO(3), a spontaneously generated loop of light is created that
      provides a coupling mechanism between the two input beams, resulting in two phase
      conjugate outputs. This behavior is discussed, and the phase-conjugate
      reflectivities are presented as a function of the ratio of input-beam
      intensities. A simple theory is developed to describe this phenomenon, and the
      predictions are compared with experimental data.

PMID- 19741778
TI  - Picosecond photorefractive effect in BaTiO(3).
AB  - We report the observation of photorefractive index gratings written and read out
      in BaTiO(3) using single pulses of 30-psec duration and fluences of 1 to 15
      mJ/cm(2) at a wavelength of 0.532 microm. While the photorefractive gratings are
      masked during formation by large free-carrier grating, they are clearly seen from
      50 psec to many minutes following the peak in the writing beams. The rapid and
      complete formation of the photorefractive grating and the complete decay of the
      free-carrier grating on a scale of 50 to 100 psec indicate either that the
      carrier-recombination time in our sample of BaTiO(3) is less than 100 psec or
      that the mobility of the carriers is >23 cm(2)/V sec.

PMID- 19741779
TI  - Phase conjugation of low-power optical beans using liquid-crystal light valves.
AB  - A real-time hologram generated in the liquid-crystal layer of a leaky-mirror
      silicon light valve is read by the same low-intensity beams used to record it.
      For a particular geometry, one of the diffracted beams propagating away from the
      device is the optical phase conjugate of one of the original beams, thus
      permitting correction of path-propagation aberrations. Experimental results show
      correction of tilt, focusing error, and random phase aberrations.

PMID- 19741780
TI  - Correction of polarization and modal scrambling in multimode fibers by phase
      conjugation.
AB  - When polarized light is incident upon a long multimode fiber, the emerging light
      is randomly distributed among the spatial and polarization modes. We present
      experimental and theoretical results demonstrating that recovery of the spatial
      and polarization modes of the incident light takes place only when a phase
      conjugator at the fiber output preserves polarization on reflection.

PMID- 19741781
TI  - Image distortion in multimode fibers and restoration by polarization-preserving
      phase conjugation.
AB  - Image restoration after a double pass through a multimode fiber using a
      polarization-preserving phase conjugator is demonstrated. Results indicate that
      the resolution of the restored image is limited by the number of guided modes and
      that the contrast is restored only when the phase conjugator preserves
      polarization on reflection.

PMID- 19741782
TI  - Optical bistability using a Fabry-Perot semiconductor-laser amplifier with two
      holding beams.
AB  - Bistable switching of an optical signal beam by a control beam with a different
      wavelength, using the nonlinearity of a Fabry-Perot semiconductor-laser
      amplifier, is reported for the first time to the authors' knowledge. Depending on
      the initial detuning of the optical signal beam, both normal (counterclockwise)
      and reverse (clockwise) hysteresis are theoretically and experimentally obtained
      in the signal output power as a function of the control input power.

PMID- 19741783
TI  - Soliton propagation along optical fibers.
AB  - Soliton propagation along optical fibers is discussed on the basis of the
      modified nonlinear Schrodinger equation, which is known to be completely
      integrable in terms of the inverse-scattering transformation. Numerical
      observation of soliton propagation reveals various kinds of dynamical behavior,
      which cannot be accounted for by treating the nonlinear derivative term of the
      modified nonlinear Schrodinger equation as a perturbation term for the cubic
      nonlinear Schrodinger equation.

PMID- 19741784
TI  - Four-photon fiber laser.
AB  - Strong infrared optical signals at the wavelengths 0.991 and 1.149 microm were
      produced as a result of phase-matched four-photon mixing when Nd:YAG laser light
      was coupled into a <4-m-long piece of single-mode glass fiber. Stimulated gain
      was observed, and laser action was obtained with the fiber in an external cavity.

PMID- 19741785
TI  - Coupled-mode analysis of a bent birefringent fiber.
AB  - A coupled-mode analysis is presented for a bent single-mode birefringent fiber.
      The coupling coefficients are given in closed forms. The effects of bending on
      the birefringence, the polarization dispersion, and the mode coupling in a bent
      birefringent fiber are discussed. Comparisons with other authors' work are also
      made by reducing our results to the case of a bent, isotropic, single-mode fiber.

PMID- 19741786
TI  - Self-pulsing in prism coupling into planar waveguides.
AB  - Coupling argon-laser light into absorbing SiO(2)-TiO(2) waveguides, we observed
      at constant input power depending on the angle of incidence and the initial gap
      width, self-pulsing, bistability, or a special form of bistability with either a
      constant or a self-pulsing output. The system's dynamics is governed by two
      effects with different time constants, both caused by heating of the waveguide by
      the incoupled absorbed power: (1) thermal expansion of waveguide and prism, which
      reduces the coupling gap width and thus changes the incoupling efficiency, and
      (2) desorption of H(2)O molecules from the SiO(2)-TiO(2) layer, which changes the
      effective guide index.

PMID- 19741787
TI  - Analysis of an optical rib waveguide with a nonlinear substrate.
AB  - A treatment of a channel waveguide with a nonlinear, Kerr-type substrate is
      presented. A modified effective-index method was used to calculate mode indices
      and electric field distributions for the nonlinear waves.

PMID- 19741788
TI  - Direct-current bias stable Ti:LiNbO(3) TE-TM mode converters produced by
      magnesium postdiffusion.
AB  - Depression of the surface index of Ti:LiNbO(3) channel waveguides by secondary
      diffusion of MgO forms a buffer layer that optically isolates the guided modes
      from attenuation caused by electrodes placed over the guides. For x-cut, z
      propagating mode-conversion devices, we find high stability to optical drift when
      a dc voltage as high as 60 V is applied to electrodes (typical gap of 5 microm)
      to establish bias operating points. Photoconductivity is found to limit the long
      term stability. Devices operating at 0.633-microm wavelength generally suffer
      significant drift in their mode-conversion efficiency when 100 microW or more of
      throughput power is present and a bias of 14 V is used. 10-microW throughput at
      the same wavelength is found to be stable over an 8-h period. At 0.8-microm
      wavelength, bias voltages as high as 60 V may be used for stable operation even
      at 100-microW optical throughput.

PMID- 19741789
TI  - Wavelength-insensitive couplers using dispersive materials.
AB  - It is shown that the coupling coefficient in optical couplers can be made
      insensitive to wavelength by the choice of materials having appropriate
      dispersive characteristics. The coupling coefficient between the dispersive slab
      waveguides is calculated and compared with the results obtained for nondispersive
      materials.

PMID- 19741790
TI  - Mode-selective detection of optical guided waves by integrated metal-oxide-metal
      structures.
AB  - We show that a metal-oxide-metal (Al-AlO(x)-Al) tunnel junction fabricated
      directly upon a planar ion-exchange glass waveguide can be used to detect the
      guided radiation through evanescent coupling. Carriers photogenerated in the
      electrode next to the guide can be internally photoemitted over the oxide barrier
      to generate a photocurrent. Because of the greater metallic absorption of TM
      polarized modes, the process is polarization sensitive. 32-dB TM selectivity is
      achieved in a simple device.

PMID- 19741791
TI  - Dynamic optical interconnections.
AB  - An optical configuration is described that uses an addressable reflective
      component (a liquid-crystal light valve) permitting free-space interconnections
      between points located on the same substrate. The scheme is attractive for
      generating programmable interconnections between electronic elements located on
      the same chip or wafer, in particular since it is highly resistant to system
      misalignment. Experimental results indicating a fan-out capability, which is
      desirable for clock signal distribution, are presented.

PMID- 19741792
TI  - Reversible optical computing circuits.
AB  - Planar optical implementations of binary adders are developed using a three-port
      nonlinear interface device as the single computing primitive. The device is bit
      conserving and both optically and logically reversible.

PMID- 19741793
TI  - Remote polarization control for fiber-optic interferometers: erratum.

PMID- 19741794
TI  - Real-time joint transform correlator with phase conjugation for distortion
      correction.
AB  - A joint transform correlator has been demonstrated that incorporates phase
      conjugation in a BaTiO3 crystal to correct for distortions in a liquid-crystal
      television (LCTV) spatial light modulator. The optical arrangement permits real
      time operation in spite of the relative slowness of the photorefractive effect.
      Correlation outputs displayed on a video monitor are illustrated for inputs to
      the LCTV from a video camera viewing a stationary scene. The sensitivity of the
      correlator to target rotation is also presented.

PMID- 19741795
TI  - Method for measuring the spot size of a laser beam using a boundary-diffraction
      wave.
AB  - A new and simple method for measuring the spot size of a laser beam is presented.
      In this method, the spot of a laser beam is scanned transversely across a
      straight boundary, and the intensity profile of the boundary-diffraction wave is
      observed. This intensity profile makes it possible to measure the spot size. The
      spot size of a He-Ne laser beam (wavelength 633 nm) has been measured to be 8.3
      microm by using a Si3N4 straight pattern; this value is compared with 8.9 microm
      obtained by the knife-edge method.

PMID- 19741796
TI  - Integrated polarimeters based on anisotropic photodetectors.
AB  - Anisotropic detectors (AD's) can be designed by coating a photosensitive surface
      (e.g., Si) with a birefringent thin film whose principal axes are in the plane of
      the film. An integrated polarimeter (IP) is described that uses four linear
      photodetectors, of which three are AD's. The light beam, whose Stokes parameters
      (SP's) are to be measured, is relayed from one detector to the next by near
      normal-incidence partial specular reflection while remaining in one plane. By a
      suitable choice of surface properties and orientations of the AD's, the four
      output electrical signals of the four detectors determine completely and
      unambiguously all four SP's. This IP with AD's (IPAD) has all the advantages of
      the previously described four-detector polarimeter [Opt. Lett. 10, 309 (1985)].
      In addition, the IPAD offers a compact design with small-area detectors.

PMID- 19741797
TI  - In-line light-saving photopolarimeter and its fiber-optic analog.
AB  - An in-line light-saving photopolarimeter (ILLSP) is described that employs four
      highly reflecting detectors, each of which absorbs only a small polarization
      dependent fraction of the light that falls upon it. The polarimeter conserves
      most of the power and direction and possibly the polarization of the incident
      beam whose Stokes parameters it measures. The principle of operation of the ILLSP
      can be extended to apply to light guided by an optical fiber using polarization
      dependent evanescent-field coupling at four successive locations on the fiber
      that are separated by rotations induced by twists or the Faraday effect.

PMID- 19741798
TI  - Method for complete determination of a refractive-index tensor by bireflectance:
      application to CdWO4.
AB  - The bireflectance effect is observed when a light beam is internally reflected in
      an anisotropic material. Generally, an unpolarized light beam splits into four
      beams on reflection. A new method for simultaneous measurement of the three
      refractive indices, based on laser-beam splitting due to bireflectance, is
      demonstrated in the biaxial CdWO4 crystal. The three principal refractive indices
      of CdWO4 were obtained in the visible range. At Lambda = 633 nm, nX = 2.09 +/-
      0.01, nY - nX = 0.052 +/- 0.001, and nZ -nX = 0.114 +/- 0.002.

PMID- 19741799
TI  - Effect of carrier diffusion on the nonlinear response of optical waveguides.
AB  - Using a self-consistent numerical method, we calculate the carrier-density
      dependent changes in the propagation constant of a TE mode in a symmetric slab
      semiconductor waveguide. By modeling the nonlinearity with the plasma theory, the
      effect of transverse carrier diffusion on the nonlinear response of a waveguide
      is investigated for typical waveguide parameters.

PMID- 19741800
TI  - Ti-concentration inhomogeneities in Ti:LiNbO3 waveguides.
AB  - Distributed fluctuations in the effective index of a waveguide can explain all
      the nonideal optical characteristics (including optical cross talk) observed in
      Ti-diffused LiNbO3 directional-coupler switches. We find that these spatial-index
      fluctuations are not a result of the photolithographic processes used to define
      the channel waveguides. Measurements of undiffused Ti films have an envelope of
      concentration variations approximately seven times that of the diffused Ti
      channel waveguides. The magnitude of these inhomogeneities is consistent with
      that required to produce the optical cross talk in current devices.

PMID- 19741801
TI  - Long-range surface magnetoplasmons in thin nickel films.
AB  - We present the results of a theoretical and experimental investigation of long
      range surface magnetoplasmons in thin, magnetic metal films. With a transversely
      applied magnetic field, the reflectance modulation measurements from prism
      coupled modes in nickel films are in agreement with the theory. The reflectance
      modulation is the same order of magnitude for prism-coupled long-range and single
      interface magnetoplasmons.

PMID- 19741802
TI  - Surface wave induced high transparency of an overdense warm plasma layer.
AB  - We have found conditions in which a structure consisting of an overdense warm
      plasma layer spaced between two underdense warm plasma layers becomes transparent
      to a p-polarized obliquely incident electromagnetic wave. The energy of the
      incident wave is transferred across the overdense region by a pair of coupled
      surface waves.

PMID- 19741803
TI  - Propagation velocity of laser-induced plasma inside and outside a transparent
      droplet.
AB  - The supersonic propagation velocity of the emission front of plasma produced by
      laser-induced breakdown of a micrometer-sized transparent droplet flowing in a
      gas was measured with a streak camera at three intensity levels. At low input
      intensity, the plasma velocities in the gas away from and toward the shadow face
      were determined. At medium input intensity, the plasma velocities in the gas
      outside the shadow face and within the liquid (traveling toward the illuminated
      face) were measured. At high input intensity, the plasma velocities in the gas
      outside the shadow face, within the liquid, and in the gas outside the
      illuminated face were deduced.

PMID- 19741804
TI  - Second-harmonic generation in amorphous vinylidene cyanide/vinyl acetate
      copolymer using a pulsed Nd:YAG laser.
AB  - Second-harmonic generation was recently observed in an amorphous vinylidene
      cyanide/vinyl acetate copolymer film by using a pulsed Nd:YAG 1.06-microm laser.

PMID- 19741805
TI  - Intensity dependence of two-wave mixing absorption in a resonant medium.
AB  - Two-wave mixing absorption in a supersonic beam containing I2 has been studied.
      The results are in agreement with theory for probe intensities comparable with
      the pump intensity. However, at very low probe-beam intensities, the absorption
      deviates substantially from the predicted value and becomes the same as that for
      the pump beam alone. We believe that this behavior is caused by density
      variations in the molecular beam and suggest that this effect can be developed
      into a tool for probing optical inhomogeneities on a microscopic scale.

PMID- 19741806
TI  - Self-organized phase-matched harmonic generation in optical fibers.
AB  - We generated second-harmonic light from a single-mode fiber after a few minutes
      of seeding with 532-nm harmonic light along with 1.064-microm pump light. This
      experiment supports a mechanism for photoinducing an alternating second-order
      nonlinearity in the fiber.

PMID- 19741807
TI  - Observation of self-focusing in optical fibers with picosecond pulses.
AB  - Self-focusing was observed at Raman frequencies, using picosecond pulses
      propagating in a large-core optical fiber of 100-microm diameter. For intense
      input pulses, a continuum of Stokes frequencies was generated in a small ring
      waveguide structure. The ring diameter of 11 microm was about 10 times smaller
      than the beam diameter at low intensities. The ring structure was attributed to
      an induced-gradient-index profile arising from the nonlinear index of refraction.

PMID- 19741808
TI  - Picosecond and femtosecond pulse generation near 1000 nm from a frequency-doubled
      Nd:YAG-pumped cw dye laser.
AB  - We report efficient synchronous mode locking of a 532-nm pumped cw dye laser
      tunable from 840 to 1030 nm, using a styryl compound as the gain medium. Hybrid
      synchronously pumped, passive mode locking of the laser using the saturable
      absorber DaQTeC generated 230-fsec pulses near 975 nm.

PMID- 19741809
TI  - Storage and phase conjugation of multiple images using backward-stimulated echoes
      in Pr3+:LaF3.
AB  - We have observed long-term storage and phase conjugation of multiple images by
      using a backward-stimulated echo scheme in the 3H4 -3Po transition of Pr3+:LaF3
      crystal. The temporal order of the multiple-echo images is the reverse of that of
      the input images. Each of the echo images is a phase-conjugate replica of the
      input images and lasts as long as IS sec. This constitutes, in principle, the
      movie using a stimulated photon echo.

PMID- 19741810
TI  - Measurement of difference deformation using speckle interferometry.
AB  - An application of speckle interferometry is presented that allows one to compare
      the resistance to stress of two nominally identical specimens. The interference
      pattern gives contours of equal differences in displacements of the two stressed
      specimens. The method is briefly developed, and its experimental feasibility is
      demonstrated by comparing the deflections of two square plates clamped along the
      edges and subjected to centrally concentrated loads.

PMID- 19741811
TI  - Hierarchical multistability and cooperative flip-flop operation in a bistable
      optical system with distributed nonlinear elements.
AB  - A bistable optical system with distributed nonlinear elements is proposed. Novel
      functions are derived from the collective nature of the optical elements.
      Collective phenomena including spatial period-doubling bifurcations, hierarchical
      multistabilities, and various types of cooperative all-optical flip-flop
      operations are predicted to take place in the proposed optical device.

PMID- 19741812
TI  - Five new 3-microu m laser lines in YAlO3:Er.
AB  - Five new laser lines at lambda = 2.7118, 2.8230, 2.8400, 2.8665, and 2.8756 pm
      were found in a YAlO3:Er (10 or 20%) crystal laser operated at 300 K. Tuning of
      the laser cavity in favor of the new transitions was performed with polarizing,
      birefringent, and selectively absorbing filters.

PMID- 19741813
TI  - Injection behavior of high-power broad-area diode lasers.
AB  - A single-mode diode laser is injected into a high-power broad-area diode laser to
      produce single-mode operation with 80 mW in a 0.50 degrees-wide far-field lobe.
      Spectrally resolved near- and far-field measurements suggest a simple Fabry-Perot
      amplifier model that qualitatively explains the observed injection and beam
      steering behavior in these devices as well as gain-guided multiple-stripe arrays.
      This model provides criteria for the optimization of injection performance.

PMID- 19741814
TI  - Pump-induced population changes in broadband coherent anti-Stokes Raman
      scattering.
AB  - Using a powerful, excimer-laser-pumped broadband coherent anti-Stokes Raman
      scattering (CARS) system, we have observed considerable changes in the
      populations of room-temperature nitrogen under atmospheric pressure. Pump-induced
      populations in the first, second, and third vibronic bands of N2 at room
      temperature resulted in an apparent vibrational temperature of 2550 K. The
      implications for broadband N2 CARS thermometry are discussed.

PMID- 19741815
TI  - Polarization-based optical parallel logic gate utilizing ferroelectric liquid
      crystals.
AB  - We describe parallel optical XOR and XNOR logic gates implemented with
      ferroelectric liquid-crystal (FLC) electro-optic elements to yield naturally a
      logic in which the binary gate outputs are indicated by two orthogonal
      polarizations of transmitted light. These gates absorb no power from the incident
      light beam and hence can be cascaded without the need to regenerate NOT inputs.
      The FLC elements also confer the advantages of low-voltage, low-power,
      submicrosecond switching and intrinsic two-state memory. Experimental results
      demonstrating the XOR and XNOR function are presented, along with measurements of
      the percentage of polarized light rotated into the two binary states.

PMID- 19741816
TI  - Stability of solitons in birefringent optical fibers. I: equal propagation
      amplitudes.
AB  - The effect of birefringence on soliton propagation in single-mode optical fibers
      is considered. Emphasis is on solitons with multipicosecond widths that are
      appropriate for communications applications. It is shown that while linear
      birefringence will lead to a substantial splitting of the two polarizations over
      20 km, this effect can be eliminated by use of the Kerr nonlinearity. Above a
      certain amplitude threshold, the central frequency of each polarization shifts
      just enough to lock the two polarizations together.

PMID- 19741817
TI  - Influences of the drawing conditions on optical characteristics in undoped-silica
      core single-mode fibers.
AB  - The influences of the drawing conditions on the optical characteristics of
      undoped-silica-core/fluorine-doped-silicaclad single-mode fibers are
      investigated. The optical loss depends strongly on the drawing conditions.
      Moreover, the cutoff shifts to lower wavelengths with an increase in the drawing
      tension because of the drawing-tension-induced decrease in refractive-index
      differences.

PMID- 19741818
TI  - Polarization-mode interferometry in birefringent single-mode fibers.
AB  - An interferometric technique was used to investigate the relative phase delay
      between polarization modes in birefringent single-mode fibers. Polarization-mode
      dispersion is directly deduced from the measurements of relative phase delay at
      different wavelengths. Relative group delays of 20 fsec can be measured in meter
      length samples without the need for light-polarizing devices.

PMID- 19741819
TI  - Dispersion compensation in coherent fiber-optic communications.
AB  - Linear filtering techniques in coherent communications systems appear to offer a
      useful method for increasing the bandwidth in dispersion-limited fiber-optical
      signal propagation. These techniques are described, and the requirements on
      filter performance are outlined. Bandwidth is shown to be related to the square
      root of the filter figure of merit.

PMID- 19741820
TI  - Cross-phase modulation in optical fibers.
AB  - When pulse pairs copropagate in a fiber, each pulse chirps the other through
      cross-phase modulation (XPM). In particular, XPM causes spectral broadening of
      signal pulses during Raman or parametric optical pulse amplification. We have
      studied XPM experimentally in the fiber Raman amplification soliton laser. We
      show that experimentally observed spectra can be explained by a simple model that
      concentrates on the phase change as a function of pulse walk-off.

PMID- 19741821
TI  - Soliton at the zero-group-dispersion wavelength of a single-model fiber.
AB  - It is shown that solitons emerge from initial pulses of arbitrary shape and
      amplitude whose central frequencies are at the zero-dispersion point. The initial
      threshold power is substantially reduced from that required for experiments to
      date. The use of these solitons is thus an attractive alternative to both the
      linear and the nonlinear communication schemes that have been proposed to date.

PMID- 19741822
TI  - Characteristics of dual-shape core fiber with an alpha-index center core.
AB  - The bending-loss and dispersion-sensitivity characteristics of a dispersion
      shifted dual-shape core fiber with an alpha index center core are described.
      Calculations show that these characteristics can be improved by decreasing a and
      that a bend-optimized, dual-shaped core fiber exhibits a small bending loss and a
      large mode field diameter.

PMID- 19741823
TI  - Compact, low-loss, fused biconical taper couplers: overcoupled operation and
      antisymmetric supermode cutoff.
AB  - The automated manufacture and characterization of compact four-port highly
      overcoupled fused couplers is reported. During the pulling stage of the
      manufacturing process, the light power in such devices is observed to cycle back
      and forth up to 1000 times between the two output ports for elongations smaller
      than 20 mm. For sufficiently long pulls, antisymmetric supermode cutoff has been
      observed for the first time to our knowledge, manifested by a sudden cessation of
      the coupling process. The measured wavelength dependence of the coupling ratio
      together with the device dimensions are consistent with the observation of cutoff
      as observed in pull-signature characteristics.

PMID- 19741824
TI  - Improved optical local-oscillator isolation using multiple acousto-optic
      modulators and frequency diversity.
AB  - A technique is described and experimental evidence presented for obtaining
      ultrahigh isolation between the optical local oscillator and the transmitter in
      heterodyne systems. A degree of isolation that results in an equivalent fed-back
      optical signal that is more than 200 dB below the transmitted power level has
      been achieved.

PMID- 19741825
TI  - Using the Hotelling trace criterion for feature enhancement in image processing.
AB  - A method of adaptive, nonlinear filtering that enhances the features that
      separate two sets of images has been developed. The method uses the Hotelling
      trace criterion to find the optimal linear feature operator for the Fourier
      moduli of the images. This operator is then used as a filter in the Fourier
      domain such that the features that separate the two classes of objects are
      enhanced. We demonstrate the use of this filtering method to enhance texture
      features in simulated liver images from nuclear medicine, after using a training
      set of images to obtain the filter. We also demonstrate how this method of
      filtering can be used to reconstruct an object from a single photon-starved image
      of it, when the object contains a repetitive feature.

PMID- 19741826
TI  - Biphotonic process for recording holograms with continuous-wave lasers in the
      near infrared.
AB  - A new process that permits the recording of holograms produced by laser sources
      emitting in the near infrared is presented. The recording process involves the
      sensitization of singlet oxygen and the oxidation of an adapted trap. Finally, a
      second photon initiates a photopolymerization, which induces changes in
      refractive index and creates the hologram.

PMID- 19741827
TI  - Absorption holograms made with mode-stabilized laser diodes for use in a
      satellite communications link.
AB  - An experimental technique is presented for constructing absorption holograms in
      IR-sensitive material with mode-stabilized laser diodes. The combination of an
      extremely sensitive recording medium and high power available from the diode is
      exploited to permit minimum exposure times. This prevents the inherent modal
      instability of the laser diode from becoming a problem while the interference
      pattern is recorded. Diffraction efficiencies into the first order were measured
      to be greater than 14% for small construction angles, indicating some phase
      effects. These absorption holograms will be used as the first step in a two-step
      process to produce holographic optical elements for use with laser diodes in a
      satellite communications link.

PMID- 19741828
TI  - Incidental motion in interferometry of phase objects.
AB  - The effect of incidental motion of optical elements or of a phase object for
      interferometry of phase objects is examined. Estimates of maximum in-plane and
      out-of-plane displacements for speckle interferometry and holography
      interferometry are made. Measurements of fringe visibility are presented that
      give qualitative agreement with the estimates.

PMID- 19741829
TI  - Feedback-induced first-order Freedericksz transition in a nematic film.
AB  - It is shown that optical-electrical feedback can transform the Freedericksz
      transition in a nematic film from second order to first order. The criteria that
      indicate whether the Freedericksz transition is first or second order are
      obtained. The hysteresis accompanying the first-order transition versus the
      feedback intensity is discussed. The feedback-induced first-order Freedericksz
      transition has been observed experimentally. The experimental results are in good
      agreement with the theoretical analysis.

PMID- 19741830
TI  - Design of a magneto-optic slab isolator for integrated optics.
AB  - The problem of a nonreciprocal phase shifter comprising a magneto-optic slab is
      formulated using scaled parameters. Nonreciprocity is attributed to polarization
      effects in TM modes propagating in asymmetric waveguides under an applied
      external magnetic field. Simple design guidelines are presented for an isolator
      that uses these propagation effects.

PMID- 19741831
TI  - Persistent spectral hole burning due to deuteron tunneling in SrF(2):Pr(3+):D(-).
AB  - We report the observation of persistent spectral hole burning due to a mechanism
      that is new to inorganic materials, i.e., light-induced deuteron (or proton)
      tunneling. Measurements were made on (3)H(4) ? (1)D(2) transitions of
      SrF(2):Pr(3+) centers having two D(-) ions as near neighbors. The spectral holes
      exhibit hyperfine structure dominated by very large (~100-MHz) pseudoquadrupole
      splittings in the singlet ground state.

PMID- 19741832
TI  - Time-resolved measurements of short-wavelength fluorescence from x-ray-excited
      ions.
AB  - We demonstrate a novel technique for time-resolved spectroscopic studies of
      highly excited ions. The technique uses a laser-produced plasma as a short-pulse,
      soft-x-ray light source with a high repetition rate. A Nd:YAG laser with a pulse
      duration of 90 psec, a pulse energy of 70 microJ, and repetition rate of 10(4)
      pulses per second is focused onto a rotating metal target. Soft x rays from the
      resulting plasma photoionize a gas surrounding the target, and fluorescence from
      the gas is detected by using a spectrometer and a high-speed photodetector. Using
      the technique of time-correlated photon counting, we determined the radiative
      lifetime and collisional quenching rate of the Xe III 5s(0)5p(6)(1)S(0) state by
      observing its fluorescence at 108.9 nm. A time resolution of better than 400 psec
      was obtained. We also measured relative Auger decay yields of a core hole state
      in xenon using a higher-energy laser-produced plasma light source at a lower
      repetition rate.

PMID- 19741833
TI  - Doppler-free two-photon absorption spectroscopy with a frequency-modulated dye
      laser.
AB  - A new method of Doppler-free two-photon spectroscopy has been developed in which
      a frequency-modulated (FM) dye laser is used to perform high-resolution
      spectroscopy. This provides an ideal method of locking a broadband FM laser to a
      narrow atomic or molecular reference line, a necessary step in using the FM laser
      for optical-frequency metrology. The method may also be used to test how closely
      the FM dye laser approaches a pure FM oscillation.

PMID- 19741834
TI  - Repeated quantum measurements on a single-harmonic oscillator.
AB  - Repeated quantum measurements on the intracavity field of a lossless micromaser
      are discussed. The effect of the associated quantum state reductions is to
      generate photon statistics bearing little relation to the original ones or to
      those obtained if no measurement is performed.

PMID- 19741835
TI  - Acousto-optic modulator as an electronically selectable unidirectional device in
      a ring laser.
AB  - An acousto-optic modulator causes unidirectional operation of dye and Ti:sapphire
      ring lasers. The modulator has a low insertion loss in the cavity and can be used
      to switch the direction of the beam electronically. The ring-laser performance is
      characterized, and experiments to probe the origin of the unidirectional
      operation are described.

PMID- 19741836
TI  - Population inversions in C IV in a recombing theta-pinch plasma.
AB  - Population inversions on the 5g-4f and 4f-3d transitions of C IV at 253.0 and
      116.9 nm have been observed in the recombination phase of a theta-pinch plasma
      initially containing 14 mTorr of acetylene and 0.5 mTorr of hydrogen gas.
      Population ratios of 17:11:1 for the 5g, 4f, and 3d levels were deduced from
      measured absolute line intensities of the 5g-4f and 4f-3d, and 3d-2p transitions
      at 253.0, 116.9, and 38.4 nm. The resulting gain-length product for a single pass
      through the 23-cm-long plasma column, based on the measured Doppler-broadened
      linewidth, is 2.3% at 116.9 nm and 5.8% at 253.0 nm.

PMID- 19741837
TI  - Continuous-wave operation at 2.1 microm of a diode-laser-pumped, Tm-sensitized
      Ho:Y(3)Al(5)O(12) laser at 300 K.
AB  - Room-temperature operation of a continuous-wave Tm-sensitized Ho:YAG laser at
      2.0974 microm has been achieved under diode-laser pumping at 781.5 nm. Observed
      thresholds are as low as 4.4 mW, with a slope efficiency of 19% with 0.5% output
      coupling.

PMID- 19741838
TI  - 65-femtosecond pulse generation from a synchronously pumped dye laser without a
      colliding-pulse mode-locking technique.
AB  - Optical pulses as short as 65 fsec have been successfully generated from a
      synchronously pumped dye laser that does not employ a colliding pulse mode
      locking technique. The laser consists of a linear cavity with two dye jets (a
      gain jet with R6G and a saturable absorber jet with DODCI and DQOCI) and a four
      Brewster-angled-prism sequence. A spatial filter between the pairs of prisms
      plays an important role in achieving saturable-absorber mode locking around 615
      nm. The pulse has a spectral width of 8.0 nm, and the average power is 100 mW at
      a repetition rate of 76 MHz for a pump power of 1.2 W at 532 nm.

PMID- 19741839
TI  - Passive mode locking of a continuous-wave energy-transfer dye laser operating in
      the near infrared around 750 nm.
AB  - The passive mode locking of an argon-ion-pumped energy-transfer cw dye laser
      operating in the near infrared is reported. The dyes 1,1'-diethyl-4,4'
      carbocyanine iodide and 1,1'-diethyl-2,2' -dicarbocyanine iodide were used
      separately to mode lock a gain medium comprising the dyes DCM and Rhodamine 700.
      Subpicosecond pulses were generated from 732 to 761 nm in a simple linear cavity,
      and pulses as short as 110 fsec were obtained from a colliding pulse mode-locked
      ring cavity that was tuned between 742 and 754 nm.

PMID- 19741840
TI  - Hysteretic three-photon cyclotron resonance in semiconductors.
AB  - We predict a hysteretic three-photon cyclotron resonance in narrow-gap
      semiconductors driven by two laser beams with their frequency difference near the
      cyclotron frequency. This effect is based on the Doppler and Lorentz nonlinear
      mechanisms and the nonparabolicity of the conduction band. A CO(2) laser
      intensity of 10(5)-10(6) W/cm(2) at 10.6 and 9.4 microm is required for
      observation of the effect at 83.03 microm in InSb, GaAs, or HgTe.

PMID- 19741841
TI  - Gain and noise characteristics of a continuous-wave Raman laser.
AB  - The spectrum of the stimulated electronic Raman gain at 650 nm in Ne I, pumped by
      a 633-nm He-Ne cw laser in the same cavity, is derived. The question of the
      proper Raman-gain linewidth is addressed. It is shown that the gain has a nearly
      Doppler-free component whose width is measured as 30 +/- 10 MHz (FWHM) at 6 Torr.
      This value agrees reasonably well with the residual Doppler broadening but not
      with collisional broadening rates. A simple calculation is included that shows
      the quantum-limited frequency uncertainty of the 650-nm laser to be higher by a
      factor of 1.5 than the frequency uncertainty of the 633-nm laser at equal power.

PMID- 19741842
TI  - Sodium phase-conjugate oscillator in a combusting environment.
AB  - We report on the use of a sodium-seeded flame as an amplifying phase conjugator.
      The environment is unique in that a number density of 10(16) cm(-3) is maintained
      despite a lateral dimension of 1 mm. We combine two of these optically pumped
      flames to form a phase-conjugate resonator. Finally, we observe oscillation that
      is due to the action of a single flame and two pump beams.

PMID- 19741843
TI  - Diffusive transverse coupling between adjacent InSb transphasor channels.
AB  - The proportionality of a transphasor signal to the photoexcited carrier density
      has been utilized to measure the transfer of the signal between adjacent optical
      channels and to estimate practical transphasor packing densities (~10(3) cm(-2))
      for a pure, bulk etalon of InSb, 280 microm thick. By using the transphasor as a
      probe of the carrier population distribution produced by an adjacent beam, the
      ambipolar diffusion length was measured as 74 microm.

PMID- 19741844
TI  - Isolas in the three-photon optical excitation of a single cyclotron electron.
AB  - We show that sufficiently strong laser beams with two frequencies differing by a
      cyclotron frequency of a free electron can give rise to strong cyclotron
      excitation with prohibited and allowed cyclotron orbits as well as to an optical
      Stark shift. This is due to a combination of relativistic effects and results in
      multiple isolated branches of excited motion (isolas). The formation of the first
      three-photon isola, when lambda(cyclotron) approximately 2 mm and lambda(laser)
      approximately 10 microm, can be observed with the laser power as low as congruent
      with 10 mW.

PMID- 19741845
TI  - Dynamic reflectivity switching of infrared lasers by an inhomogeneous plasma.
AB  - The effect of an inhomogeneous electron-hole plasma in a semiconductor on the
      reflection properties at the infrared is theoretically investigated. For an
      exponential density profile, it is shown that enhanced dynamic reflectivity
      diminishes significantly for relatively shallow plasma depths. These results can
      be used to design reflection plasma switches for the production of ultrashort
      infrared-laser pulses.

PMID- 19741846
TI  - Spatial light modulation by beam coupling in GaAs crystals.
AB  - We present the first reported demonstration of spatial light modulation in GaAs
      using the photorefractive effect. The demonstration was done with a special
      configuration in which polarization rotation created by beam coupling was
      utilized.

PMID- 19741847
TI  - Efficient two-photon-resonant frequency conversion in mercury: the effects of
      amplified spontaneous emission.
AB  - Numerical modeling of two-photon-resonant sum-frequency mixing in mercury vapor
      predicts efficiencies >10% for generation of 130.2-nm oxygen resonance light. The
      modeling indicates that power broadening of the two-photon resonance due to
      amplified spontaneous emission from the pumped level strongly influences the
      mixing process. Measurements of the broadening and the efficiencies for
      difference-frequency mixing are presented as a check of the model calculations.

PMID- 19741848
TI  - Double-color-pumped photorefractive oscillator and image color conversion.
AB  - Can two laser beams of different colors interact with each other to initiate a
      photorefractive oscillation in a slowly responding (~1 sec) crystal? We report on
      the operation of this new nondegenerate four-wave mixing device, in which two
      other beams and the gratings are efficiently self-generated. An application for
      image color conversion is demonstrated. In an experiment, we used for the two
      pumps combinations of the lines of an argon-ion laser (514.5, 496.5, 488, 476.5,
      and 457.9 nm) and a He-Ne laser (632.8 nm). The mixing crystal was BaTiO(3) with
      a photorefractive time constant of the order of 1 sec.

PMID- 19741849
TI  - Semi-self-pumped phase-conjugate mirrors.
AB  - We describe semi-self-pumped photorefractive phase-conjugate mirrors based on the
      unidirectional ring resonator and the double phase-conjugate mirror. Their
      applicability to thresholding phase conjugation and one-way imaging through
      distortions is discussed.

PMID- 19741850
TI  - Experimental and numerical results of optical subpulse formation of long optical
      pulses in monomode fibers.
AB  - Using a mode-locked Nd:YAG laser with a pulse width of ~100 psec, we find that a
      broad temporal pulse undergoes a transition to a trainlike formation of subpulses
      when propagating through a dispersive and dissipative monomode optical fiber.
      This process does not require an additional optical seed pulse or noise from
      spontaneous emission.

PMID- 19741851
TI  - Analysis of frequency-doubling processes in optical fibers using Raman
      spectroscopy.
AB  - We have experimentally found a correlation between the nonlinear characteristics
      of frequency-doubling optical fibers and a specific modification of their Raman
      spectra. We propose a tentative interpretation of the physical origin of these
      phenomena, based on the assumption of the existence of small Si-O rings inside
      the fiber material. These structures would explain the nonzero value of the
      second-order nonlinear susceptibility.

PMID- 19741852
TI  - Polarization fluctuation in optical fibers based on probability.
AB  - Polarization fluctuations are measured in submarine and underground cables and in
      long-haul fibers as long as 270 km. The fluctuations are discussed in terms of
      probabilities using the Poincare sphere. When the fluctuations are small, the
      distribution of the polarization state on the Poincare sphere closely matches a
      normal two-dimensional distribution. To compensate automatically for the
      fluctuations, an endlessly rotatable polarization controller is used.

PMID- 19741853
TI  - Fiber-optic bipolar tap implementation using an incoherent optical source.
AB  - A fiber-optic bipolar tap implementation is described. The proposed scheme
      utilizes 2's complement-number representation and digital multiplication by an
      analog convolution algorithm. Simple experimental verification of the scheme is
      presented. The addition of programmability to the taps results in the realization
      of a fast, flexible processor for manipulating binary quantities.

PMID- 19741854
TI  - Use of highly elliptical core fibers for two-mode fiber devices.
AB  - The four complex, almost degenerate, second-order eigenmodes of a two-mode fiber
      having a circular core are reduced to two nondegenerate, linearly polarized
      second-order eigenmodes with stable-intensity lobe positions in a highly
      elliptical core fiber. Existing two-mode-fiber devices can be improved by this
      stabilization of the second-order modes. Practical sensors employing the two
      spatial modes as the two arms of an interferometer are described. The two arms of
      an interferometer of this type can have the same group delays, while the
      difference in phase delays is large.

PMID- 19741855
TI  - Strain effects on highly elliptical core two-mode fibers.
AB  - Longitudinal strains in optical fibers have been found to produce a large
      differential phase shift between the first-and second-order spatial modes
      propagating in a two-mode fiber. This differential phase shift between the modes
      is both calculated and measured to be dispersive with respect to wavelength. For
      fibers with highly elliptical core geometries, which propagate only one lobe
      orientation of the second-order mode, the differential phase shift is also found
      to be polarization dependent.

PMID- 19741856
TI  - Phase delay of coupled modes in single-mode optical fibers.
AB  - The phase delay of the fundamental LP(01) mode in a single-mode optical fiber is
      studied using periodic perturbation of the fiber axis. A large phase shift may be
      obtained through distortion-induced birefringence, with less than 1.5- dB
      coupling loss to the radiative modes.

PMID- 19741857
TI  - Measuring the refractive-index profile of optical fibers by the cladding-mode
      near-field technique.
AB  - A new measurement system has been developed that simply determines the refractive
      index profile of any optical fiber by analyzing the propagation of cladding
      modes. Measurement accuracy was verified by a comparison with the refractive near
      field method, and a sufficient resolution level was achieved to produce the fine
      structural details in single-mode fibers.

PMID- 19741858
TI  - Wavelength referencing in single-mode microbend sensors.
AB  - The strong wavelength dependence of microbending losses in single-mode fibers is
      utilized in wavelength referencing for fluctuation-free microbend sensors.
      Through fiber size and microbend periodicity, optimization of the wavelength
      dependence can be increased dramatically. The reference and signal wavelengths
      can be provided through the spectrum of a light-emitting diode.

PMID- 19741859
TI  - Extended-range fiber polarimetric strain sensor.
AB  - We describe a frequency-modulation technique that is applicable to two-beam
      interferometric systems illuminated by semiconductor diode lasers. The technique
      permits a determination of the optical path difference between the two arms of
      the interferometer and is used here to extend the range of a fiber polarimetric
      strain sensor by determining the order of the particular polarimetric fringe
      under consideration.

PMID- 19741860
TI  - Propagation phenomena of nonlinear film guided waves in a configuration with
      material losses: a numerical analysis.
AB  - The propagation of TE-polarized nonlinear guided waves excited at different
      points of the nonlinear dispersion curve has been examined along a thin film
      bounded by two identical self-focusing media with linear absorption. The
      evolution of the fields indicates that the stable branches of the nonlinear
      dispersion curve can be passed through when the total energy flow decreases
      because of absorption. The evolution of nonstationary waves initially excited at
      unstable branches of the dispersion curve shows significant dependence on the
      magnitude of the absorption.

PMID- 19741861
TI  - Power-transfer effects in monomode optical nonlinear waveguiding structures.
AB  - We describe power-transfer effects, over a certain threshold, among constituents
      of planar waveguiding structures consisting of an optical linear layer deposited
      onto a nonlinear substrate (CdS(x)Se(1-x)-doped glass). Proper selection of the
      thickness of the linear waveguiding film and the refractive index of the linear
      cladding allows one to obtain optical transistor action and to construct all
      optical AND, OR, NOT, and XOR logic gates. The effects appear for the TE(0)
      guided mode.

PMID- 19741862
TI  - Optical emission from impurities within an epitaxial-silicon optical waveguide.
AB  - Beryllium pairs form an isoelectronic complex in crystalline silicon that can
      bind an exciton. At sufficiently low temperatures, this bound exciton radiates in
      a narrow line near the wavelength lambda = 1.15 microm. We report the observation
      of optical confinement of this bound-exciton emission from beryllium impurities
      introduced, by ion implantation, into an epitaxial-silicon optical waveguide.

PMID- 19741863
TI  - Measured TM-TM coupling in waveguide gratings.
AB  - We report measurements of the guided-wave reflectivity of a periodic, surface
      corrugation, waveguide grating as a function of incidence angle and polarization.
      We show that the measured response is more accurately described by a coupled-mode
      theory based on the local-normal-mode expansion of the fields than by that based
      on the ideal-mode expansion.

PMID- 19741864
TI  - Operator methods in optics: paraxial propagation in inhomogeneous media, an exact
      treatment.

PMID- 19741865
TI  - Four-channel polarimeter for time-resolved ellipsometry.
AB  - A new four-channel partial polarimeter was designed for use in time-resolved
      ellipsometry measurements. The device outputs four parallel, equispaced beams
      from a single input beam. By detecting and digitizing the intensities of these
      four beams, the intensity, as well as two of the three elements of the reduced
      Stokes vector can be determined. Since there are no moving parts to the
      polarimeter, time resolution is limited only by the response time of the
      photodetectors and the digitizers. The linear array of output beams is ideal for
      streak-camera detection, yielding a potential time resolution of ~1 psec. A beam
      splitter is described that separates the input beam into two beams, which are
      parallel to the input beam and whose polarizations are nearly the same as the
      input beam. In addition, the polarimeter is achromatic, operating in the
      wavelength region from 220 to 1100 nm.

PMID- 19741866
TI  - Photorefractive spatial light modulation by anisotropic self-diffraction in
      KNbO(3) crystals.
AB  - Photoinduced anisotropic self-diffraction in photorefractive KNbO(3) has been
      studied. It has been shown that this type of diffraction is ideally suited for
      spatial light modulation or incoherent-to-coherent conversion. A phase grating
      that is photoinduced by two coherent light beams causes the diffraction of one of
      the beams. By spatially modulating the amplitude of the phase grating with an
      incoherent signal beam it is possible to transfer an incoherent image onto the
      coherent self-diffracted beam. The performance parameters of this modulator are
      described with a simple model.

PMID- 19741867
TI  - All-fiber-optic remote sensing of temperature employing interferometric
      techniques.
AB  - An all-fiber interferometric temperature sensor capable of remote operation is
      described in which the fiber's sensing element is configured as a Fabry-Perot
      cavity of typically less than 5 mm situated at the end of a lead fiber of
      arbitrary length (typically 2 m). The sensing element is addressed through a
      fiber coupler, permitting both remote detection and multiplexing of a number of
      sensing elements for multiple-point measurements.

PMID- 19741868
TI  - Time-division multiplexing of interferometric fiber sensors using passive phase
      generated carrier interrogation.
AB  - The multiplexing and demodulation of interferometric sensors using a time
      division/phase-generated carrier approach is described. The scheme uses slightly
      unbalanced interferometers and laser frequency modulation to effect the
      interrogation of the sensors, while the time-division multiplexing allows
      individual sensors to be addressed. Phase sensitivities of ~20 microrad/
      radicalHz and cross-talk levels of <-47 dB are demonstrated for a three-sensor
      network.

PMID- 19741869
TI  - Ti:LiNbO(3) waveguide electro-optic beam combiner.
AB  - We demonstrate a low-loss Ti:LiNbO(3) waveguide circuit for lambda = 1.55 microm
      that under voltage control can be used to combine two mutually coherent input
      beams of arbitrary relative amplitude and phase into a single-output waveguide
      while suffering only propagation losses.

PMID- 19741870
TI  - Frequency response of thermo-optic tuning mechanism of planar silica optical
      multiplexer.
AB  - The thermo-optic mechanism provides a simple means of tuning the wavelength of
      interferometric optical multiplexers constructed from planar silica waveguides
      upon a silicon substrate. Frequencydomain measurements of the tuning response
      permit an understanding of the tuning mechanism that is relevant to the design of
      components for applications in which wavelength-tracking error and cross-talk
      penalty are important. Measurements on a prototype device have shown a primary
      low-pass breakpoint at 360 Hz but have also highlighted the possibility of
      secondary mechanisms affecting the low-frequency response. A continually
      increasing phase lag at higher frequencies has also been detected and must be
      allowed for in control-circuit design.

PMID- 19741871
TI  - Three-terminal noninverting optoelectronic logic device.
AB  - A novel noninverting optoelectronic logic device using a GaAs/AlGaAs multiple
      quantum-well modulator is demonstrated that combines electronic nonlinearity with
      optical input and output and is bistable. The device is bistable but displays
      hard limiting and an optical gain of 12.

PMID- 19741872
TI  - Optoelectronic switch matrix as a look-up table for residue arithmetic.
AB  - The use of optoelectronic matrix switches to perform look-up table functions in
      residue arithmetic processors is proposed. In this application, switchable
      detector arrays give the advantage of a greatly reduced requirement for optical
      sources by comparison with previous optoelectronic residue processors.

PMID- 19741873
TI  - Design of transparent optical networks by using novel quantum amplifiers and
      sources.
AB  - It is shown how the photon-number amplifier may be used to make, for either novel
      or conventional sources, an efficient direct-detection receiver and transceiver
      in a local-area network environment and how the parametric amplifier may be used
      similarly for a homodyne-detection receiver.

PMID- 19741874
TI  - Optical precision profilometer using the differential method.
AB  - A novel optical precision profilometer, which is nearly independent of vertical
      vibrations, is proposed. It can make simultaneous height measurements of both a
      measurement position and its surroundings and perform subsequent digital
      subtraction of the latter from the former. The noise level of this profilometer
      on the table with steady vibrations of 0.4 gal (1 gal = 10 (-2) m/sec(2)) is 0.05
      nm root mean square. Data obtained from measurements of an optical flat and a Si
      wafer are included.

PMID- 19741875
TI  - Full-field modeling of the longitudinal electro-optic probe.
AB  - Optical polarization changes and mode coupling due to spatially varying
      anisotropic perturbations in caused by electro-optic, acousto-optic, and other
      effects have been widely studied for both plane-wave and fiber mode propagation.
      A new optical S-parameter analysis of these effects, applicable to arbitrary
      optical field distributions, is presented. It is applied to evaluating the
      performance of the longitudinal electro-optic probe used for noninva-sively
      examining GaAs integrated circuits. Error in probe measurements of circuit
      voltage distributions can be characterized by considering the probe as a scanned
      electro-optic spatial filter.

PMID- 19741876
TI  - Absolute excited-state absorption cross section and fluorescence quantum
      efficiency of Cr(3+):gadolinium scandium gallium garnet.
AB  - Excited-state properties of the laser material Cr(3+):Gd(3)Sc(2)(GaO(4))(3) were
      determined by a photocaloric technique. The excited-state absorption cross
      section at 650 nm is (3.6 +/- 0.6) 10(-20) cm(2), and the fluorescence quantum
      efficiency at ambient temperature is (91 +/- 1)%.

PMID- 19741878
TI  - Statistical distribution of frequency fluctuations in semiconductor lasers.
AB  - We present experimental results showing a departure from the usually assumed
      Gaussian statistics of the fluctuations of the instantaneous emission frequency
      in single-mode semiconductor lasers operating under the influence of an external
      optical feedback. The amount of this departure is studied and analyzed under
      various operating conditions.

PMID- 19741877
TI  - Analysis of frequency chirping of semiconductor lasers in the presence of optical
      feedback.
AB  - The frequency chirping of a single-mode semiconductor laser in the presence of
      optical feedback is studied by rate-equation analysis. The model includes the
      amplitude-phase-coupling and spectral-hole-burning effects. A simple analytical
      formula is obtained in the small-signal regime that shows that the amplitude
      phase-coupling effect also enhances the chirp-reduction ratio and that the
      maximum reduction of frequency chirping can be achieved at the same time as
      maximum line narrowing in the in-phase condition.

PMID- 19741879
TI  - Noise propagation from pump to secondary lasers.
AB  - Experimental measurements of the intensity fluctuations and the associated power
      spectra for the pump (argon) laser and the secondary (dye) laser show that the
      secondary laser follows pump fluctuations when operated far above threshold but
      acts as a low-pass filter when operated close to threshold. The experimental
      results are well explained by a laser model that accounts for pump fluctuations
      through a multiplicative colored-noise process. The theory and the experiment are
      in good quantitative agreement.

PMID- 19741880
TI  - Continuous-wave operation of a room-temperature, diode-laser-pumped, 946-nm
      Nd:YAG laser.
AB  - Single-stripe diode-laser-pumped operation of a continuous-wave 946-nm Nd:YAG
      laser with less than 10-mW threshold has been demonstrated. A slope efficiency of
      16% near threshold was shown with a projected slope efficiency well above a
      threshold of 34% based on results under Rhodamine 6G dye-laser pumping. Nonlinear
      crystals for second-harmonic generation of this source were evaluated. KNbO(3)
      and periodically poled LiNbO(3) appear to be the most promising.

PMID- 19741881
TI  - Continuous-wave operation of extremely low-threshold GaAs/AlGaAs broad-area
      injection lasers on (100) Si substrates at room temperature.
AB  - Room-temperature continuous-wave operation of large-area (120 microm x 980
      microm) GaAs/AlGaAs graded-refractive-index separate-confinement heterostructure
      lasers on (100) Si substrates has been obtained. Minimum threshold-current
      densities of 214 A/cm(2) (1900-microm cavity length), maximum slope efficiencies
      of about 0.8 W/A (600-microm cavity length), and optical power in excess of 270
      mW/facet 900-microm cavity length) have been observed under pulsed conditions.

PMID- 19741882
TI  - Amplifier/compressor fiber Raman lasers.
AB  - We show that the chirp from cross-phase modulation (XPM) dominates the operation
      of fiber Raman lasers (FRL's). Thus a FRL in the anomalous group-velocity regime
      is best described as a XPM-chirped Raman amplifier followed by a linear fiber
      compressor. While the output of such a laser is generally a narrow pulse with a
      broad pedestal, we show both experimentally and by computer simulation that
      negligible background is achievable.

PMID- 19741883
TI  - Subpicosecond-pulse generation in a synchronously mode-locked ring color-center
      laser.
AB  - Data are presented for the operation of a versatile color-center laser that
      permitted the generation of stable trains of subpicosecond pulses in a
      synchronously pumped ring configuration. With LiF:F(2)(+) as the gain medium,
      pulses having durations of 0.7 psec (Gaussian pulse shape assumed) were reliably
      obtained with average powers of 15-20 mW available in each of the two output
      beams. These pulse widths are more than a factor of 2 shorter than those obtained
      when this laser was configured with a standing-wave resonator.

PMID- 19741884
TI  - InGaAs/GaAs multiquantum-well electroabsorption modulator with integrated
      waveguide.
AB  - A monolithically integrated guided-wave modulator has been realized by using
      molecular-beam epitaxial regrowth and ion-milling techniques. The guiding and
      modulating regions consist, respectively, of In-doped GaAs and
      GaAs/In(0.34)Ga(0.66)As strained-layer multiquantum wells. Modulation is achieved
      by field-enhanced electroabsorption in the multiquantum wells. The insertion loss
      of the modulator is 0.9 dB, and the transmission loss in the guides is </=1
      dB/cm. The temporal response of similar GaAs/InGaAs as-grown photodiodes to
      pulsed laser excitation is characterized by a rise time of 115 psec.

PMID- 19741885
TI  - Spread-spectrum nonlinear-optical interactions: quasi-phase matching with
      pseudorandom polarity reversals.
AB  - Optical nonlinear interactions may be made broadband while maintaining a high
      conversion efficiency by applying spread-spectrum pseudorandom spatial
      modulation.

PMID- 19741886
TI  - Exact field decomposition for TM waves in nonlinear media.
AB  - We show that the electric field components E(x) and E(z) of a transverse magnetic
      (TM) wave propagating in a nonlinear medium can be formally decomposed through a
      conservation law, provided that partial differentialxx/ partial
      differentialE(z)(2) = partial differentialzz/ partial differentialE(x)(2). If
      this condition is satisfied, then the electromagnetic field distribution can be
      exactly obtained by quadrature. For the case of a guided nonlinear TM mode, our
      procedure can be employed to establish the eigenvalue equation directly.

PMID- 19741887
TI  - Effect of nonlinear boundary conditions on nonlinear phenomena in optical
      resonators.
AB  - The question of proper boundary conditions at the surface of a nonlinear medium
      is discussed. It is shown that the nonlinearity of the boundary conditions could
      have a significant effect for large fields. Thus the nonlinear boundary
      conditions significantly affect the transmission behavior near the upper
      bistability threshold.

PMID- 19741888
TI  - Observation of optical bistability in CdS(x)Se(1-x)-doped glasses with 25-psec
      switching time.
AB  - We report the first observation to our knowledge of optical bistability in
      CdS(x)Se(1-x)-doped glasses with rise and fall times of 25 psec for bistable
      switching. The third-order nonlinear susceptibility chi((3)) was estimated
      experimentally to be 1.3 x 10(-9) esu, which is in good agreement with the value
      reported previously. The high-speed switching and value of chi((3)) show that the
      bistability is caused by an optical nonlinearity that is attributed to the band
      filling effect.

PMID- 19741889
TI  - Phase conjugation by self-pumped Brillouin-induced four-wave mixing.
AB  - We report the first observation to our knowledge of self-pumped Brillouin-induced
      four-wave mixing in a manner analogous to self-pumped four-wave mixing in
      BaTiO(3). Using carbon disulfide as a scattering medium, we have observed both
      double and treble Brillouin-shifted conjugate beams.

PMID- 19741890
TI  - Measurements of stimulated Brillouin scattering phase-conjugate fidelity.
AB  - We describe high-accuracy measurements of stimulated Brillouin scattering phase
      conjugate fidelity. The dependence of fidelity on pump intensity and on pump-beam
      divergence is in rough agreement with theoretical predictions for the low
      reflectivity limit, even for operation deep into the saturation regime.

PMID- 19741891
TI  - Efficient solution of Maxwell's equations for optical fibers with arbitrary
      refractive-index profiles.
AB  - A straightforward method of solving vectorial wave equations in terms of electric
      fields for cylindrically symmetrical optical fibers is described. Input profiles
      are modeled by functions with continuous derivatives, so all fields are
      continuous. To iterate propagation constants, a generalized secant method is
      used. Numerical integrations are performed with a published FORTRAN code based on
      a fourth/fifth-order Runge-Kutta method. Techniques that help to make
      calculations efficient are presented. By using an IBM personal computer,
      propagation constants of actual single-mode fibers are found with 11-digit
      computational accuracy in 2 min each. Finally, the scalar wave equation is also
      solved efficiently.

PMID- 19741892
TI  - Measurement of the group-delay difference between the principal states of
      polarization on a low-birefringence terrestrial fiber cable.
AB  - We report some results of measurements of the frequency dependence of the state
      of polarization at the end of a low-birefringence long-cabled (50-km) optical
      fiber. The principal states of polarization and their group-delay difference were
      determined by making use of the Poincare sphere representation.

PMID- 19741893
TI  - Dispersion cancellation using linearly chirped Bragg grating filters in optical
      waveguides.
AB  - The use of a linearly chirped Bragg grating filter for dispersion cancellation in
      an optical-fiber link is discussed. Numerical and theoretical calculations are
      made, which show that, with the proper taper function, the filter can have a high
      reflectivity and a quasi-constant nonzero dispersion, proportional to the inverse
      of the chirp. The filter can compress dispersion-broadened pulses by factors of 2
      5 or more, if many filters are cascaded. Its compactness and efficiency would
      make it suitable for on-line implementation.

PMID- 19741894
TI  - Stroboscopic phase-shifting interferometry.
AB  - The implementation of a new type of phase-shifting, self-referencing
      interferometer that simultaneously achieves the phase shift and separation of
      heams with a stationary diffraction grating is described. The capabilities of
      stroboscopic interferometry are demonstrated with results from an experiment in
      which the rapidly varying surface deformations of a sonically activated pellicle
      mirror are measured in a time-sliced fashion at 50-microsec intervals.

PMID- 19741895
TI  - Image synthesis from nonimaged laser-speckle patterns.
AB  - We demonstrate that unspeckled images of coherently illuminated, diffuse objects
      can be formed from measurements of backscattered laser-speckle intensity. The
      theoretical basis for this imaging technique is outlined, and results of computer
      experiments that successfully construct images from digitally simulated laser
      speckle measurements are presented.

PMID- 19741896
TI  - Velocity measurements by vibrational tagging and fluorescent probing of oxygen.
AB  - We report the development of a new method of instantaneously measuring three
      dimensional velocity profiles and structure in air and oxygen. No seeding of
      particles, molecules, or atomic species is required. The method combines Raman
      excitation and laser-induced electronic fluorescence to generate a time-gated
      image of the moving oxygen molecules.

PMID- 19741897
TI  - Frequency-modulation spectroscopy of rubidium atoms with an AlGaAs diode laser.
AB  - Frequency-modulation (FM) spectroscopy has been performed on the D(2) transitions
      of rubidium atoms with an AlGaAs diode laser at 780 nm. Doppler-broadened
      hyperfine-structure transitions of (85)Rb and (87)Rb were resolved with no
      residual amplitude-modulation-induced background signal by modulating the
      injection current of the laser diode at a low frequency (20-50 MHz) compared with
      the Doppler width. To obtain Doppler-free spectra, we combined FM spectroscopy
      with saturation spectroscopy. The results show that the FM spectroscopy technique
      is sensitive and should be useful for high-resolution spectroscopy, although the
      resolution was instrument limited and unusual double peaks were observed.

PMID- 19741898
TI  - Sub-Doppler tunable far-infrared spectroscopy.
AB  - The first experimental observations to our knowledge of sub-Doppler linewidths in
      a cell made using tunable far-infrared radiation are reported. A double-resonance
      scheme has been used, combining CO(2)-laser infrared radiation with tunable far
      infrared radiation to observe a sub-Doppler line shape in an excited vibrational
      state of CH(3)OH.

PMID- 19741899
TI  - Continuous-wave Rayleigh-Brillouin-gain spectroscopy in SF(6).
AB  - We have obtained cw Rayleigh-Brillouin-gain spectra of SF(6) for both forward and
      backward scattering geometry with high spectral resolution. The spectral
      resolution is better than 4 MHz, and a Brillouin-frequency shift as small as 42
      MHz is clearly resolved. Extension of the present technique to other studies is
      discussed.

PMID- 19741900
TI  - Device for simultaneous multiple-line mode locking of an argon-ion laser.
AB  - An acousto-optic device that can simultaneously mode lock multiple lines of a
      laser source has been designed and demonstrated. The device is an intracavity
      acousto-optic modulator with an end mirror. Multiple argon-ion laser lines at
      476.5, 488.0, 496.5, and 514.5 nm were simultaneously modulated by using this
      device. Pulse trains with pulses having a width of approximately 100 psec FWHM at
      a repetition of 130 MHz were obtained for each line.

PMID- 19741901
TI  - Frequency stabilization of semiconductor lasers by resonant optical feedback.
AB  - With simple optical geometries a separate resonant Fabry-Perot cavity can serve
      as an optical feedback element that forces a semiconductor laser automatically to
      lock its frequency optically to the cavity resonance. This method is used to
      stabilize laser frequencies and reduce linewidths by a factor of 1000 from 20 MHz
      to approximately 20 kHz.

PMID- 19741902
TI  - Alternative approach to stable lasers: the optically pumped NH(3) laser.
AB  - A beat-note stability of 500 Hz over 1 sec has been observed between two free
      running optically pumped NH(3) lasers. The 12-microm laser frequency is strongly
      isolated from cavity-mirror motion and is relatively insensitive to perturbations
      in the pump lasers.

PMID- 19741903
TI  - Pulsed, room-temperature operation of a tunable NaCl, color-center laser.
AB  - A room-temperature, pulsed, color-center laser using OH(-)-doped NaCl crystals is
      reported. Crystals were transversely pumped by a Q-switched Nd:YAG laser at
      1.06microm and produced output energies of 8.6 mJ in 20-nsec pulses. The tuning
      range extended from 1.37 to 1.77 microm. During 40 h of operation (>10(6)
      pulses), a gradual power fading was observed. Laser action is tentatively
      ascribed to F(2)(+) centers.

PMID- 19741904
TI  - Stimulated emission in optically pumped atomic-copper vapor.
AB  - We have observed, for the first time to our knowledge, stimulated emission in
      atomic-copper vapor that is excited by a resonant tunable laser beam. One of the
      important and interesting results obtained in this experiment is that excitation
      of the (2)P(1/2) level of the copper atoms generates strong amplified spontaneous
      emission (ASE) for both(2)P(1/2)-(2)D(3/2) and (2)P(3/2)-(2)D(5/2) transitions.
      This is the first reported direct experimental evidence observed for collisional
      mixing between the (2)P(1/2) and (2)P(3/2) levels in a copper-vapor laser.
      Excitation of the (2)P(3/2) level induces substantially weaker ASE for the
      (2)P(1/2)-(2)D(3/2) transition. In addition, we observed collision-induced ASE
      for both transitions over a wide range of detuning of the pump frequency. The
      preliminary results of the experiment are presented, and the implications of the
      results for high-pressure copper-vapor lasers are discussed.

PMID- 19741905
TI  - High-gain erbium-doped traveling-wave fiber amplifier.
AB  - Traveling-wave amplification of a lambda = 1.53 microm signal with +22-dB gain is
      achieved at 295 K in an Er(3+)-doped single-mode fiber using a lambda = 514.5 nm
      pump source. The optimum fiber length for maximum gain is determined
      experimentally. A limit in signal-to-noise ratio that is due to concurrent
      amplification of spontaneous emission is observed. By cooling the fiber to 77 K,
      the amplifier gain is increased to +29 dB as a result of depopulation of the
      lower laser level.

PMID- 19741906
TI  - Saturation of the Xe III 109-nm laser using traveling-wave laser-produced-plasma
      excitation.
AB  - We describe the construction and operation of a 109-nm, photoionization-pumped,
      single-pass laser in Xe III. The laser is pumped by soft x rays emitted from a
      laser-produced plasma in a traveling-wave geometry. Using a 3.5-J, 300-psec, 1064
      nm laser pump pulse, we measure a small-signal gain coefficient of 4.4 cm(-1) and
      a total small-signal gain of exp(40). The laser is fully saturated and produces
      an output energy of 20 microJ in a beam with 10-mrad divergence.

PMID- 19741907
TI  - Observation of super Coster-Kronig-pumped gain in Zn III.
AB  - We report the observation of laser gain in the vacuum ultraviolet pumped by super
      Coster-Kronig decay. Using a 5-J, 300-psec pump pulse of 1064-nm radiation, we
      have observed gain on transitions in Zn III at 127.0, 130.6, and 131.9 nm with
      total gains of exp(2.4), exp(5.1), and exp(3.2), respectively. The large
      branching ratios of the rapid super Coster-Kronig decay into a small number of
      final levels makes high-efficiency operation possible.

PMID- 19741908
TI  - Mutual coherence of two coupled multiline continuous-wave HF lasers.
AB  - Two multiline cw HF lasers employing unstable resonators were coupled by
      injecting 20% of each laser output into the other laser. The mutual coherence of
      the two output beams was measured by recording the visibility V of the
      interference fringes generated when the beams are overlapped. Both single-line
      and multiline interference patterns were observed. The output from the two lasers
      in the present experiment (20% coupling) was completely coupled, indicating that
      the achievement of stable coupling is not dependent on careful adjustment of the
      length of each laser resonator.

PMID- 19741909
TI  - X-ray transition radiation in a solid-state superlattice: photoabsorption,
      electron scattering, and radiation optimization.
AB  - Soft x rays are generated when low-energy electron beams traverse a solid-state
      superlattice. We investigate the influence of x-ray absorption and electron
      scattering losses on the maximum power radiated, the required electron energy,
      and the optimum total thickness of the superlattice. We show that a moderate
      increase in the electron-beam energy compensates for the losses due to
      photoabsorption and electron scattering.

PMID- 19741910
TI  - Passively mode-locked color-center laser.
AB  - Passive mode locking of a cw (chopped) color-center laser using a saturable
      absorber polymethine cyanine dye is reported for the first time to our knowledge.
      By employing the dye IR 140 for passive mode locking, we have obtained stable
      output trains of pulses from a LiF:F(2)(+) laser at wavelengths around 870 nm.
      When the technique of colliding-pulse mode locking was implemented in a ring
      cavity configuration, pulses having durations as short as 390 fsec were
      generated.

PMID- 19741911
TI  - Picosecond amplification in wide-aperture KrF lasers.
AB  - An output energy of 350 mJ has been extracted with a pulse width of 20 psec from
      two wide-aperture (7 cm x 7 cm) discharge KrF amplifiers. The entire system was
      well synchronized with 1-nsec time jitter. The amplified spontaneous emission was
      as low as 3% of the energy because of the relatively low small-signal gain of
      3.9%/cm in the amplifier modules.

PMID- 19741912
TI  - Shortening of KrF(*) laser pulses using stimulated Brillouin scattering.
AB  - Pulses as short as 43 psec were generated by Brillouin backscattering at 248 nm
      in cyclohexane. The measurements show that the process is accompanied by
      considerable spectral broadening of the reflected radiation.

PMID- 19741913
TI  - Subharmonic resonances in higher-order collision-enhanced wave mixing in a sodium
      seeded flame.
AB  - Using four-, six-, and eight-wave-mixing geometries, we observe subharmonic
      resonances in collision-enhanced spectra in a sodium-seeded hydrogen-air flame.
      Appearing at high intensity, these resonances occur at +/-1/2, +/-1/3, +/-1/4,
      and +/-1/5 times the frequency of the ground-state hyperfine splitting
      omega(hfs). We argue that these resonances result from higher-order processes,
      specifically chi((n)), where n >/= 5. In particular, to describe the resonances
      at +/-omega(hfs)/5, at least chi((13)) is required. These high-order collision
      enhanced effects are true perturbative nonlinearities and not sequential four
      wave mixing processes.

PMID- 19741914
TI  - Controlled scanning of a continuous-wave dye laser with an intracavity
      photorefractive element.
AB  - An intracavity photorefractive crystal is used in a cw dye laser. The frequency
      selection of the grating written in the crystal by the laser's standing-wave
      intensity pattern reduces the laser spectrum to a pair of hole-burning modes. The
      wavelength can be tuned by varying the laser-cavity length. Wavelength scans
      across an entire gain curve are possible without mode hops.

PMID- 19741915
TI  - All-optical flip-flop operation in an optical bistable device using two lights of
      different frequencies.
AB  - All-optical flip-flop operation in a Fabry-Perot-type optical bistable device
      (OBD) is investigated. The OBD is switched both from OFF to ON and ON to OFF
      using two lights of different frequencies as trigger pulses. We present the
      theoretical calculation, obtained by applying a conventional expression for a
      dispersive OBD to the two-light input case, and the experimental observation, in
      which a semiconductor laser amplifier is used as a bistable device.

PMID- 19741916
TI  - Modulation instability in an extended nonlinear Schrodinger equation.
AB  - The modulation instability of an extended nonlinear Schrodinger equation was
      investigated. It was found that the odd-order higher dispersion [beta(3)] does
      not contribute to the modulation-instability frequency. The time derivative of
      the nonlinearity was included and shown to affect the instability. Finally,
      nonlinear retardation effects are shown to alter the results significantly.

PMID- 19741917
TI  - Decay of femtosecond higher-order solitons in an optical fiber induced by Raman
      self-pumping.
AB  - We have numerically solved an extended version of the nonlinear Schrodinger
      equation, taking into account higher-order dispersion, the shock (self
      steepening) term, and a term describing the Raman self-pumping of an ultrashort
      pulse. It is shown that the Raman effect is dominant on a femtosecond time scale
      and leads to the decay of higher-order solitons. For the case of the N = 2
      soliton an intense pulse at a distinctly Stokes-shifted frequency is created.
      This pulse eventually shapes into a fundamental soliton, and its further
      evolution is governed by the combination of dispersion, self-phase modulation,
      and the soliton self-frequency shift.

PMID- 19741918
TI  - Cascade Raman soliton fiber ring laser.
AB  - Pulses as short as 200 fsec at 1.5 microm and 230 fsec at 1.6 microm have been
      generated through a cascade Raman, solitonlike process in a fiber ring
      oscillator. A dispersion-shifted (lambda(0) = 1.46 microm) single-mode fiber was
      used as the gain medium, which was synchronously pumped by a cw mode-locked
      Nd:YAG laser operated at 1.32 microm.

PMID- 19741919
TI  - Fiber-optic frequency shifter using a grating acoustic scanner.
AB  - A fiber-optic single-sideband frequency shifter using a grating acoustic scanner
      has been demonstrated. By using the surface-wave-to-bulk-wave conversion
      mechanism of a LiNbO(3) scanner, a traveling acoustic bulk wave with a frequency
      of approximately 42 MHz was generated and was incident at an angle upon an
      optical fiber. This angle is adjustable by changing the surface-wave frequency to
      produce phase-matched coupling between two polarization modes or two spatial
      modes of light in the fiber. An optical coupling efficiency of approximately 70%
      and carrier and image sideband suppression of 18 and 35 dB, respectively, were
      realized.

PMID- 19741920
TI  - Waveguide-dispersion characteristics of dual-shape-core dispersion-shifted
      fibers.
AB  - Waveguide-dispersion characteristics are discussed experimentally and
      numerically. The waveguide dispersions of both dual-shape-core (DSC) and graded
      index types of dispersion-shifted fibers are evaluated from the measured
      wavelength dependence of the mode field radius. It is shown that the dispersion
      sensitivity to core-radius change of a bend-optimized DSC fiber is smaller than
      that of the graded-index dispersion-shifted fiber.

PMID- 19741921
TI  - Beat-length measurement of birefringent optical fibers.
AB  - We present a novel technique for the measurement of the beat length of
      birefringent single-mode fibers based on differential attenuation induced by a
      metal. The proposed technique is particularly suited for the measurement of local
      birefringence in polished-fiber semiplates. The technique should also find
      application in the characterization of polished fiber semiplates used in the
      fabrication of fiber directional couplers.

PMID- 19741922
TI  - MgO:LiNbO(3) single-crystal fiber with magnesium-ion in-diffused cladding.
AB  - A Mg-ion in-diffusion process was applied to form an optical guiding structure in
      LiNbO(3) single-crystal fibers. A parabolic refractive-index profile was formed
      in a 56-microm-diameter, c-axis MgO:LiNbO(3) fiber, yielding quasi-single-mode
      (two modes) propagation.

PMID- 19741923
TI  - Measurement of mode field radius in axially nonsymmetrical single-mode fibers
      with arbitrary power distribution.
AB  - A new method for the measurement of mode field radius in axially symmetrical and
      nonsymmetrical single-mode fibers with non-Gaussian power distribution is
      proposed. It is based on monitoring the power passed through a variable-width
      slit in the far field. A few results for different types of single-mode optical
      fiber are presented.

PMID- 19741924
TI  - Selective interferometric sensing by the use of coherence synthesis.
AB  - A technique is discussed and demonstrated whereby the sensitivity of an
      imbalanced fiber-optic interferometric sensor is changed by as much as 70 dB by
      modifying the power spectrum and thus the coherence function of the input optical
      source. This phenomenon is then extended and used to monitor selectively single
      sensors in a small fiber-optic ladder array by synthesizing coherence functions
      that result in a high sensitivity for the sensor to be observed but a low
      sensitivity for all the others. Limitations of the demonstrated implementation
      are discussed and possible future designs presented.

PMID- 19741925
TI  - Determination of the optical anisotropy of magnetic garnet films.
AB  - We show that the application of isotropic coupling prisms instead of birefringent
      prisms permits the precise determination of the optical anisotropy of magnetic
      garnet films; these measurements are essential for phase matching and conversion
      of optical modes. Using this technique, the anisotropy of a (211)-oriented film
      was measured with silicon prisms.

PMID- 19741926
TI  - Amplitude and phase modulation by free-carrier injection in III-V semiconducting
      waveguides for the 10.6-microm wavelength.
AB  - We give experimental results for amplitude and phase modulation by free-carrier
      injection in planar and rib waveguides at a wavelength of 10.6 microm. These
      waveguides have been formed by metal-organic chemical-vapor deposition of InP and
      GalnAs layers on InP substrates. Absorptions of 95% associated with phase shifts
      greater than 3pi have been measured for injection-current densities below 1
      A/cm(2) with a planar guiding structure and drive currents of approximately 10 mA
      for typical channel waveguides.

PMID- 19741927
TI  - Saturable nonlinear dielectric waveguide with applications to broad-area
      semiconductor lasers.
AB  - Self-focusing in a passive dielectric waveguide with a saturable nonlinearity is
      studied. The eigensolutions constitute a good approximation to the lateral modes
      of broad-area semiconductor lasers under low-duty-cycle pulsed conditions. The
      laser modes are predicted to consist of adjacent filaments coupled in phase,
      leading to a single-lobed far field, and to be stable with increased current
      injection above saturation intensity. The ultimate filament spacing is inversely
      proportional to the threshold gain, and thus wider filaments are expected in low
      threshold broad-area lasers.

PMID- 19741928
TI  - Architectural and performance considerations for a 10(7)-instruction/sec
      optoelectronic central processing unit.
AB  - Architectural considerations for a multiple-instruction, single-data-based
      optoelectronic central processing unit operating at 10(7) instructions per second
      are detailed. Central to the operation of this device is a giant fiber-optic
      content-addressable memory in a programmable logic array configuration. The
      design includes four instructions and emphasizes the fan-in and fan-out
      capabilities of optical systems. Interconnection limitations and scaling issues
      are examined.

PMID- 19741929
TI  - Fiber-optic matrix multiplier using a two-dimensional systolic-array
      architecture.
AB  - An optical matrix multiplier based on a two-dimensional systolic-array
      architecture is described, exploiting the parallelism offered by optical methods.
      Experimental verification of multiplier performance is presented. A technique for
      multiple matrix multiplications is suggested.

PMID- 19741930
TI  - Implementation of Boolean logic gates using a microchannel spatial light
      modulator with liquid-crystal televisions.
AB  - A programmable optical system that can perform binary Boolean logic operations
      with a microchannel spatial light modulator (MSLM) is presented. The MSLM is used
      as an adder, an inverter, a subtractor, or a buffer. We used three liquid-crystal
      televisions with a computer as input interfacing devices. Through the use of its
      feedback loop, the system can consecutively execute a series of logic operations.
      Experimental results are provided.

PMID- 19741931
TI  - Programmable hybrid parallel processing for real-time digital logic operations.
AB  - Programmable optical parallel processing based on array logic is demonstrated by
      using optoelectronic hybrid circuits. Space-invariant and space-variant Boolean
      logic operations of all kinds can be performed in real time. The space-variant
      operation is performed according to instruction light patterns.

PMID- 19741932
TI  - Triple-in double-out optical parallel logic processing system.
AB  - A triple-in double-out optical logic operating system based on shadow-casting
      processing is described. All the 256 logic operations of three inputs can be
      performed, and the optical adder can be easily implemented. A real-time encoding
      method for the input patterns is also presented.

PMID- 19741933
TI  - Squeezing more out of a laser.
AB  - A laser's intensity can be stabilized by negative feedback from a conventional
      photodetector. I propose extraction of sub-shot-noise light from the feedback
      loop at a beam splitter by illuminating the back side of the beam splitter with
      squeezed-state light.

PMID- 19741934
TI  - Monte Carlo simulations for scattering of electromagnetic waves from perfectly
      conductive random rough surfaces.
AB  - Numerical calculations of mean scattered intensities by simulation of one
      dimensional perfectly conductive random rough surfaces are presented. Results
      relative to backscattering enhancement and more accurate criteria for the
      validity of the Kirchhoff approximation are obtained. This method can also be
      used for assessing perturbative theories and for further experiments.

PMID- 19741935
TI  - Stabilized holographic recording using the residual real-time effect in a
      positive photoresist.
AB  - The weak real-time effect in a positive-resist film was used for operating an
      actively stabilized holographic setup in order to carry out the entire recording
      process in a stabilized mode. Illustrative experimental results are reported. The
      successive recording in phase of spatially shifted holographic gratings is also
      shown.

PMID- 19741936
TI  - Comparison of motionally narrowed coherent anti-Stokes Raman spectroscopy line
      shapes of H(2) with hard- and soft-collision models.
AB  - We have compared high-resolution coherent anti-Stokes Raman spectroscopy
      measurements of the Q(1) transition of H(2) with theoretical line shapes
      incorporating both Doppler broadening and motional narrowing. Least-squares fits
      varying the motional narrowing coefficient for both the hard- and soft-collision
      model yielded line shapes that agreed well with observed spectra at 295 K for
      pressures between 50 and 3050 Torr. However, the narrowing coefficient for the
      hard-collision model was pressure dependent, whereas the narrowing coefficient
      for the soft-collision model was independent of pressure and yielded an optical
      diffusion coefficient that agreed with previously measured values.

PMID- 19741937
TI  - Pulsed-laser-generated rare-gas plasma as a light source in the vacuum
      ultraviolet.
AB  - The plasma generated by focusing a 20-Hz, 330-mJ, Nd:YAG laser pulse in a rare
      gas at pressures from 1 to 6 bars is proposed as a source of a VUV continuum
      giving as many as 10(9) photons nm(-1) sec(-1) near 170 nm. Its stability makes
      it suited to VUV spectrophotometry. The pulse duration, ranging from 20 nsec for
      Ne to 40 nsec for Kr, should also permit its use in time-resolved spectroscopy.

PMID- 19741938
TI  - Population inversion in laser-produced plasmas stagnating on a radiative coolant
      of solid density.
AB  - Population inversion between the n = 3 and n = 2 levels of the Mg(+11) ion (the
      wavelength of the transition is 4.5 nm) was observed in a laser-produced plasma
      that was stagnated and rapidly cooled on a high-Z (Au) plate. The ratio of the
      population inversion was determined to be 1.4 - 1.8 when the opacity effect was
      taken into account. From the dependence of the inversion on the coolant's Z
      number, we found that the major cooling mechanism is radiative heat loss rather
      than thermal conduction to a cold inner part of the plate.

PMID- 19741939
TI  - Room-temperature, continuous-wave, 946-nm Nd:YAG laser pumped by laser-diode
      arrays and intracavity frequency doubling to 473 nm.
AB  - We report the use of GaAlAs laser-diode arrays to pump a cw Nd:YAG laser
      operating on the 946-nm (4)F(3/2) ? (4)I(9/2) transition. At room temperature,
      the lasing threshold was reached with 58 mW of absorbed pump power, and, with 175
      mW of absorbed pump power, 42 mW of output power at 946 nm was obtained in a
      TEM(00) mode by using 0.7% output coupling. In addition, pumping with an infrared
      dye laser operating in a pure TEM(00) mode was used to investigate the effects of
      reabsorption loss that are characteristic of the 946-nm laser transition. LiIO(3)
      was used as an intracavity doubling crystal, and 100 microW of blue light was
      generated by using diode-laser pumping in a nonoptimized cavity.

PMID- 19741940
TI  - High-repetition-rate Cr:Nd:GSGG active-mirror amplifier.
AB  - We have designed, constructed, and operated a 3.8-cm clear-aperture Cr:Nd:GSGG
      active-mirror amplifier. We believe this to be the first active mirror that uses
      a crystalline host and the largest-aperture Cr:Nd:GSGG amplifier yet reported. We
      have measured a small-signal gain of 1.6. The wave front has been measured and
      found to be less than three waves of defocus at repetition rates of up to 10 Hz.
      Surface displacements were measured and compared with theory. Depolarization was
      less than 2.5% at maximum power at any location in the clear aperture.

PMID- 19741941
TI  - Stress-induced tuning of a diode-laser-excited monolithic Nd:YAG laser.
AB  - We report the application of a stress-induced change in the cavity of a
      monolithic Nd:YAG laser as a means for precisely tuning the laser's emission
      frequency. By using a piezoelectric transducer to vary the applied stress, we can
      scan the laser emission frequency rapidly and monotonically over as much as 76.5
      GHz. As a consequence of the stress-induced birefringence, the device can also be
      operated simultaneously in two orthogonally polarized modes that exhibit
      different tuning rates with applied stress.

PMID- 19741942
TI  - Real-time measurements of phonon lifetime using a streak-camera-Raman-induced
      phase-conjugation method.
AB  - A novel real-time technique to measure phonon dynamics using the Raman-induced
      phase-conjugation method in combination with streak-camera technology is
      described. The technique is used to determine vibrational and optical phonon
      dephasing kinetics of CS(2), calcite, and LiNbO(3) with a temporal resolution of
      3 psec.

PMID- 19741943
TI  - Induced phase modulation of a generated second-harmonic signal.
AB  - The weak induced-phase-modulation effects on the shape and the phase of a
      generated second-harmonic signal, due to the primary signal, are investigated in
      the regime of weak conversion and with velocity dispersion and absorption
      present. In the time domain a two-peaks structure appears in the shape of the
      signal, and in the frequency domain the spectral distribution is broadened
      compared with that of the second-harmonic signal generated in the absence of
      induced phase modulation.

PMID- 19741944
TI  - Spatial instabilities, all-optical limiting, and thresholding in nonlinear
      distributed-feedback devices.
AB  - Solutions of coupled-mode equations describing intensity-induced Bragg coupling
      of counterpropagating modes in a nonlinear distributed-feedback structure may
      become spatially unstable. Instability leads to nonpassing plateaus in the
      intensity transmission characteristics. This induces strong optical limiting
      action in the transmission mode and lower thresholding in the reflection mode.

PMID- 19741945
TI  - Trapping of energy into solitary waves in amplified nonlinear dispersive systems.
AB  - A number of examples have recently been found in which stable, highly compressed
      pulses are produced in fibers on much shorter length scales than those present
      initially. These systems involve energy flow among different nonlinear waves. We
      present numerical model calculations that exhibit this compression when energy is
      pumped into the nonlinear wave. These models are simple enough to provide some
      understanding of the underlying generic behavior. We also present a theory of
      these results that relates thr length scale of the pulse to the evolution of the
      energy.

PMID- 19741946
TI  - Second-harmonic generation of a continuous-wave diode-pumped Nd:YAG laser using
      an externally resonant cavity.
AB  - We report 13% second-harmonic conversion efficiency of a 15-mW, cw, diode-laser
      pumped Nd:YAG oscillator. 2 mW of single-axial-mode 532-mm radiation was
      generated by externally resonant second-harmonic generation in a monolithic
      MgO:LiNbO(3) nonlinear crystal cavity. The measured finesse of 450 for the
      monolithic external cavity indicated that absorption and scatter losses in the
      doubler were less than 0.8%.

PMID- 19741947
TI  - Fidelity of polarization and spatial information recovery using a fiber-coupled
      phase-conjugate mirror.
AB  - We report the investigation of polarization and spatial information recovery
      using a fiber-coupled phase-conjugate mirror. A marked dependence of the phase
      conjugate output on the input-beam conditions is experimentally observed. A
      theoretical model for these phenomena is also discussed.

PMID- 19741948
TI  - Demonstration of amplitude-distortion correction by modal dispersal and phase
      conjugation.
AB  - We demonstrate experimentally and explain theoretically polarization-preserving
      imaging through a lossy amplitude-distorting medium. This is accomplished by
      propagating the beam, before its arrival at the lossy distorting medium, through
      a (multi) mode- and polarization-scrambling fiber and reflecting the signal,
      after it has passed the lossy distorting medium, from a photorefractive phase
      conjugate mirror.

PMID- 19741950
TI  - Influence of polarization state and absorption gratings on photorefractive two
      wave mixing in GaAs.
AB  - The polarization dependence of two-wave mixing for two common crystal
      orientations is described and theoretical and experimental results given. The
      direction of energy exchange can be determined by the polarization of the two
      beams. Absorption gratings are proposed to explain fully the experimental
      results.

PMID- 19741949
TI  - Phase-conjugate multimode fiber gyro.
AB  - Phase conjugation is used to correct the detrimental effects of modal scrambling
      in a passive optical gyro that uses multimode fiber. A proof-of-principle
      demonstration of rotation sensing is presented.

PMID- 19741951
TI  - Photorefractive time differentiation of coherent optical images.
AB  - Two-beam coupling in photorefractive BaTiO(3) is used to perform time
      differentiation of time-varying coherent phase and amplitude images.
      Differentiation of one-dimensional signals and two-dimensional images is
      performed.

PMID- 19741952
TI  - Optical bistability in self-pumped phase-conjugate ring resonators.
AB  - Bistable oscillations have been observed in BaTiO(3) pumped by a single-mode 30
      mW (488-nm) argon-ion laser, which is used simultaneously as a ring passive phase
      conjugator (RPPC) and as a unidirectional ring resonator (UDRR). Strong
      oscillations in the UDRR increase the threshold coupling strength required for
      oscillation in the RPPC. The oscillations in the RPPC reduce the fanning in the
      crystal necessary for the startup of oscillation in the UDRR. Auxiliary
      resonators pumped by the RPPC are also bistable with the UDRR. Similar bistable
      oscillations have been observed when the crystal is used simultaneously as a RPPC
      and as a linear passive phase conjugator.

PMID- 19741953
TI  - High-efficiency single-pass solitonlike compression of Raman radiation in an
      optical fiber around 1.4 microm.
AB  - Highly efficient conversion (as great as 60%) into the broad first Stokes Raman
      band around 1.4 microm the 90-psec pump pulses from a cw mode-locked Nd:YAG laser
      at 1.32 microm has permitted, through a solitonlike compression mechanism in a
      single span of standard (lambda(0) = 1.3 microm) single-mode optical fiber, the
      generation of highly stable pulses of ~100 fsec, with average powers of ~30 mW in
      the solitary waves, which depend on fiber length and pump power.

PMID- 19741954
TI  - Soliton interaction in optical fibers.
AB  - Interactions of solitons generated by pairs of optical pulses are studied using
      the perturbed nonlinear Schrodinger equation, which models nonlinear optical
      pulses in a monomode fiber. We examine the mechanism of the soliton interaction
      both analytically and numerically and show that a bound 2-soliton splits into
      individual solitons traveling with different speeds because of higher-order
      effects. The numerical results are in extremely close agreement with those
      obtained recently by Mitschke and Mollenauer in their experiments on 2-solitons
      in optical fibers [Opt. Lett. 12, 355 (1987)].

PMID- 19741955
TI  - Mode-coupling analysis of anisotropic polarization-maintaining fibers.
AB  - We analyze the coupling between the fundamental vector modal fields of two
      parallel polarization-maintaining fibers. An improved coupled-mode theory is
      employed, which also applies to anisotropic materials. Results for the array-mode
      propagation constants are presented as a function of the relative tilt angle
      between the principal axes of the two fibers.

PMID- 19741956
TI  - Stochastic polarization instability: limitation to optical switching using fibers
      with modulated birefringence.
AB  - We show that the standard map governs near-separatrix evolution of the
      polarization state for an intense light wave traveling along a fiber whose linear
      birefringence has a periodic modulation. This allows us to estimate analytically,
      in good agreement with numerical experiments, the minimum angle to the unstable
      axis of a linearly polarized input beam in order to avoid chaotic power-dependent
      switching of the output polarization state.

PMID- 19741957
TI  - Waveguide propagation-loss measurement technique.
AB  - A novel nondestructive propagation-loss measurement technique for single-mode
      waveguides is demonstrated. The method calculates the total propagation-loss
      coefficient from the measured ratio of the retroreflected and transmitted light
      from the waveguide and is independent of the coupling efficiency of the input
      light. A surface-wave transducer is utilized as an acousto-optic modulator in a
      lock-in scheme to enhance the measurement ease and precision.

PMID- 19741958
TI  - Optical parallel logic gates using inexpensive liquid-crystal televisions.
AB  - The optical implementation of parallel logic gates using inexpensive liquid
      crystal televisions (LCTV's) is demonstrated, and basic experimental results are
      presented. While it is certainly unreasonable to expect general-purpose optical
      computers to be built from LCTV's, demonstration-level systems can be built, from
      which a great deal may be learned.

PMID- 19741959
TI  - Optically controlled transmission of InGaAsP epilayers.
AB  - We investigate the transmission of InGaAsP epilayers lattice matched to InP
      substrates under optical excitation at normal incidence to the surface. Near the
      gap wavelength (lambda = 1.3 microm) we observe a transmission change of 20% for
      a 0.5-mW pump beam at a wavelength lambda(2) = 790 nm. Switching dynamics are
      shown to be limited by carrier lifetimes of tau approximately 2 nsec. A simple
      analysis based on parabolic bands and direct electronic transitions provides a
      good description of the experiments.

PMID- 19741960
TI  - Determination of molecular orientation at the surface of an aerosol particle by
      morphology-dependent photoselection.
AB  - The orientation of fluorescent molecules on the surface of an aerosol particle
      has been determined by using a new technique, morphology-dependent
      photoselection. The excitation spectrum of the angularly averaged fluorescence
      from a single levitated particle is measured by using an integrating sphere
      levitator. By utilizing the relative intensities of resonant peaks in this
      spectrum and knowledge of the polarization properties of different resonances, we
      show that the orientation of molecules relative to the surface normal may be
      obtained.

PMID- 19741961
TI  - Spectral shifts produced by source correlations.
AB  - Statistical correlations of the light emitted by a partially coherent source can
      produce frequency shifts in the spectrum observed in the far field if the
      correlation function of the emitted radiation does not satisfy a certain scaling
      law. A Fourier achromat is used to generate a secondary source in which the
      degree of spectral coherence is independent of wavelength; i.e., it violates the
      scaling law. The spectrum detected in the far zone of the secondary source is, in
      general, found to be displaced in frequency and distorted relative to the
      spectrum measured at the secondary source. The displacement can be toward the
      higher frequencies or the lower frequencies depending on the direction of
      observation.

PMID- 19741962
TI  - In situ monitoring technique for fabrication of high-quality diffraction
      gratings.
AB  - We describe a simple technique that permits reproducible fabrication of high
      quality diffraction gratings with short periods. This technique utilizes in situ
      monitoring of diffracted light from photoresist gratings during the development
      process and provides optimum endpoint detection for this process. The
      effectiveness of the technique has been demonstrated through the fabrication of a
      distinct grating with a 255-nm period on a GaAs substrate.

PMID- 19741963
TI  - Optical characteristics of a deformable-mirror spatial light modulator.
AB  - Some of the optical characteristics of a recently developed solid-state
      deformable-mirror spatial light modulator have been investigated. The device is
      composed of an array of 128 x 128 pixels, with each pixel consisting of four
      hinged reflective rectangular surfaces. Modulation at video frame rates has been
      achieved, providing real-time displays in coherent light, which may be useful for
      a variety of optical processing and computing applications.

PMID- 19741964
TI  - Near-infrared-to-visible image conversion using a Si liquid-crystal light valve.
AB  - A real-time near IR-to-visible image converter using a Hughes silicon liquid
      crystal light valve (Si LCLV) has been demonstrated. A 1.06-microm image was
      converted to a 0.633-microm laser wavelength. The major advantages of this near
      IR-to-visible image converter are its high sensitivity, broad bandwidth, coherent
      (incoherent-) to-coherent (incoherent) image conversion, up and down wavelength
      conversion capability, high resolution (>10(5) resolution elements), room
      temperature operation, and high damage threshold.

PMID- 19741965
TI  - High-intensity infrared power measurements by double-resonance phosphorescence
      depletion in biacetyl vapor.
AB  - A novel technique for power measurements in high-intensity infrared beams has
      been developed. A pulse of 443-nm laser radiation prepares an excited state of
      biacetyl vapor seeded into an atmosphere of nitrogen. This state phosphoresces
      with a quantum yield of 0.15. A high-intensity infrared beam is partially
      absorbed by the excited state, which depletes the phosphorescence. Monitoring of
      this depletion permits a measurement of the infrared intensity with a temporal
      resolution of less than 1 msec. The technique is demonstrated at 1.06 microm, and
      extension to additional infrared wavelengths is discussed.

PMID- 19741967
TI  - Statistical properties of a laser with multiplicative noise.
AB  - Effects of multiplicative noise on the laser instability in a He-Ne laser are
      investigated by photon-counting measurements. Several new features, such as the
      shift of the threshold of laser oscillation and intensity fluctuations in excess
      of unity, are observed. Our measurements also reveal the importance of the
      nonlinearity of light-matter interaction even for negative pump-parameter values.

PMID- 19741966
TI  - Fiber external-cavity injection laser with a dispersive single-mode coupler.
AB  - An injection laser with an external dispersive cavity, which uses a selective
      single-mode coupler as a mode discriminator, has been designed. Narrow-linewidth
      operation has been achieved with an output power of 5 mW.

PMID- 19741968
TI  - Intracavity femtosecond-pulse compression with the addition of highly nonlinear
      organic materials.
AB  - It is experimentally shown that using organic materials of high nonlinear
      refractive index dissolved in a saturable-absorber solution permits femtosecond
      pulse compression in a simple colliding-pulse mode-locked laser employing cavity
      mirror dispersion adjustment.

PMID- 19741969
TI  - Continuous method for measuring the electro-optic coefficient in Bi(12)SiO(20)
      and Bi(12)GeO(20).
AB  - A technique for accurate measurement of the linear electro-optic coefficient(s)
      in crystals that are simultaneously optically active and birefringent is
      described. It is shown that this technique provides a direct method of measuring
      field-induced birefringence and so can form the basis of a Bi(12)SiO(20) (or
      Bi(12)GeO(20)) sensor arrangement. The high degree of accuracy obtained in the
      measurements of the linear electro-optic coefficient in Bi(12)SiO(20) and
      Bi(12)GeO(20) crystals indicates the particular suitability of these materials in
      electric-field and voltage-sensor systems with a high dynamic range and for
      possible waveguiding applications.

PMID- 19741970
TI  - Narrow nonlinear-optical resonances in CdSSe-doped glass.
AB  - We describe frequency-domain spectroscopy studies of glasses doped with CdS(1
      x)Se(x) using low-power cw tunable dye lasers. The results show a narrow
      resonance (4.4 kHz at room temperature) in the backward nearly degenerate four
      wave mixing spectrum, which we believe is determined by the phonon-mediated
      inverse lifetime of a deep level trap involved in the nonlinear response.

PMID- 19741971
TI  - Observation of parametric gain suppression in rotational Raman transitions of
      N(2) and H(2).
AB  - The ratio of forward Raman conversion thresholds for linearly and circularly
      polarized laser light has been measured in low-Fresnel-number configurations for
      the strongest rotational Raman transitions of N(2) and H(2). In both cases the
      ratio is found to be in the range 2.5-3, corresponding to a threshold-suppression
      factor of 1.7-2 for the linearly polarized laser light. The observed spatial
      distributions of the Stokes light also confirm the presence of suppression along
      the direction of propagation of the incident linearly polarized laser light.
      Numerical calculations are in good agreement with the experimental results.

PMID- 19741972
TI  - Experimental investigation of phase conjugation in stimulated Brillouin
      scattering of beams with mild cylindrical aberration.
AB  - We monitored transverse intensity profiles of Nd:YAG laser beams that had
      undergone stimulated Brillouin scattering (SBS) after being mildly aberrated by a
      cylindrical lens (CL). Poor phase conjugation was confirmed by the presence of
      this aberration in the SBS reflected beam after it hadretraced the incident
      beam's path through the CL. The results are consistent with the occurrence,
      during this SBS, of spatial filtering near line foci typical of cylindrical
      waberration. When two such beams with overlapping focal regions undergo SBS
      together, the distortion of one beam after SBS reflection is insensitive to that
      of the other.

PMID- 19741973
TI  - Limits to the efficiency of beam combination by stimulated Brillouin scattering.
AB  - The probability distribution function of the phase difference between two thermal
      noise-initiated stimulated Brillouin scattering beams was calculated and measured
      as a function of the correlation between the noise sources. This correlation is
      determined by the spatial overlap of the two pump beams. Perfect phase locking of
      every pair of Brillouin-scattered pulses is shown to be impossible.

PMID- 19741975
TI  - Simple theory for degenerate four-wave mixing in photorefractive media.
AB  - A simple analytic theory for degenerate four-wave mixing in photorefractive media
      is presented. The theory is valid when the backward pump-beam intensity is much
      smaller than the forward pump-beam and probe-beam intensities.

PMID- 19741974
TI  - Effect of focal intensity on stimulated-Brillouin-scattering reflectivity and
      fidelity.
AB  - We have measured the reflectivity and phase-conjugate fidelity of stimulated
      Brillouin scattering in hexane while varying the pump power and aberration. By
      directly measuring the reduction in focal intensity that is due to aberrations,
      we found that the reflectivity and the fidelity depend solely on the focal
      intensity. We were able to vary the strength of aberration, producing up to a
      factor-of-30 reduction in focal intensity. The reflectivity and fidelity
      decreased monotonically with decreasing focal intensity. There was no minimum
      amount of aberration required for accurate wave-front reversal, and the maximum
      amount was the aberration that reduced intensity to near threshold.

PMID- 19741977
TI  - Cross-polarization beam coupling in photorefractive GaAs crystals.
AB  - We report theoretical and experimental investigations on the cross-polarization
      coupling of two contradirectional laser beams in a photorefractive GaAs crystal.
      There is good agreement between these results.

PMID- 19741976
TI  - Mechanism for photorefractive phase conjugation using incoherent beams.
AB  - Two mutually incoherent extraordinary laser beams, incident upon opposite a faces
      of a BaTiO(3) crystal, generate a set of photorefractive holograms that channel
      both beams toward the +c face of the crystal, where they are internally reflected
      into the opposite channel. The resultant cross coupling of the two incident beams
      produces a pair of phase-conjugate (Phi*) beams. This new photorefractive
      interaction is characterized by reasonable Phi* reflectivities (~10-25%), good
      Phi* fidelity, and no image cross talk. The variations in Phi* reflectivity with
      crystal orientation, angles of incidence, and intensity ratio are presented. The
      formation times of the photorefractive gratings responsible for the phase
      conjugation are significantly shorter than those of other self-pumped phase
      conjugators.

PMID- 19741978
TI  - Vector solitons in birefringent nonlinear dispersive media.
AB  - It is shown that a novel class of optical solitons is possible in nonlinear
      dispersive media with birefringence.

PMID- 19741979
TI  - Nonlinear-optical loop mirror.
AB  - A nonlinear device for ultrafast processing is proposed. This device is based on
      the nonlinear propagation in a waveguide loop formed by connecting the output
      ports of a conventional coupler. The device is shown to have potentially useful
      characteristics for unequal coupling ratios and has the ability to operate on
      entire pulses when soliton effects are included.

PMID- 19741980
TI  - Power losses in optical-fiber graded-index-rod components.
AB  - The coupling of two fibers terminating in graded-index-rod lenses is analyzed. In
      particular, power losses due to angular misalignment and to the combined effects
      of lateral misalignment and spacing are discussed, assuming a Gaussian radiation
      pattern of the fibers. Criteria for the design of graded-index-rod components are
      also given.

PMID- 19741981
TI  - Temperature dependence of bend- and twist-induced birefringence in a low
      birefringence fiber.
AB  - The temperature dependence of the bend- and twist-induced birefringence in LB600
      low-birefringence fiber has been measured at lambda = 0.633 microm. The relative
      temperature dependence B = (1/beta)dbeta/dT of the bend-induced birefringence
      beta was found to be (5.7 +/- 0.2) x 10(-4) K(-1) over a temperature range from 
      5 to 70 degrees C. The relative temperature dependence A = (1/g)dg/dT of the
      twist-induced birefringence g was found to be (4.95 +/- 0.25) x 10(-4) K(-1)
      (between 22 and 150 degrees C). The measured values of A and B are in accordance
      with a relative temperature dependence (1/C)dC/dT of the stress-optic coefficient
      C equal to (4.2 +/- 0.2) x 10(-4) K(-1).

PMID- 19741982
TI  - Measurement of chromatic dispersions in Ti-diffused LiNbO(3) optical waveguides.
AB  - Chromatic dispersion properties of the Ti:LiNbO(3) optical waveguide have been
      investigated. Dispersion values of the waveguide fabricated in Z-cut LiNbO(3)
      were sigma(TE) = -2.0 fsec cm(-1) nm(-l) at a wavelength of 1.3 microm and
      sigma(TE) = -1.3 fsec cm(-1) nm(-1) at a wavelength of 1.5 microm. Measurement
      results were compared with theoretical values that take into account the bulk
      dispersion data and the waveguide dispersion characteristics.

PMID- 19741983
TI  - Dispersion relations and power-flow expressions for nonlinear modes guided by a
      multilayer symmetric dielectric structure.
AB  - The dispersion relations and the power-flow expressions are derived for nonlinear
      modes guided by a multilayer symmetric dielectric structure.

PMID- 19741984
TI  - Model for waveguide fabrication in glass by two-step ion exchange with ionic
      masking.
AB  - A theory for optical waveguide fabrication processes, in which potassium ions
      exchanged into glass are used as a mask to regulate a subsequent silver-ion
      exchange, is presented. The model is used to examine the use of this technique in
      restricting the width of narrow-channel waveguides. The diffusion of silver
      through the potassium-ion mask is calculated, and a novel method of fabricating
      buried waveguides is described.

PMID- 19741986
TI  - Comparison of Bessel and Gaussian beams.

PMID- 19741985
TI  - Associative-memory model based on neural networks: modification of Hopfield
      model.
AB  - The problem with the Hopfield associative-memory model caused by an imbalance
      between the number of ones and zeros in each stored vector is studied, and a
      modification of the Hopfield model that works well irrespective of the number of
      ones (or zeros) is proposed. This modified model can be implemented with no
      increase in memory.

PMID- 19741987
TI  - Self-reference holographic imaging using nonuniform illumination.

PMID- 19741988
TI  - Graded-index lens array matched filtering.

PMID- 19741989
TI  - Measurement of mixing fluid flows with optical tomography.

PMID- 19741990
TI  - Consummate solution to the problem of classical electromagnetic scattering by an
      ensemble of spheres. I: Linear chains.

PMID- 19741991
TI  - Spatial temperature-profile measurements by the thin-filament pyrometry
      technique.

PMID- 19741992
TI  - Instantaneous three-dimensional concentration measurements in turbulent jets and
      flames.

PMID- 19741994
TI  - Proposal for continuous white-light cooling of an atomic beam.

PMID- 19741993
TI  - Radiative processes in air excited by an ArF laser.

PMID- 19741995
TI  - Interpretation of relaxation oscillations of semiconductor lasers in terms of the
      dynamic Stark effect.

PMID- 19741996
TI  - Multipass amplification of soft x-rays in a laser cavity.

PMID- 19741997
TI  - Coherent summation of injection-locked, diode-pumped Nd:YAG ring lasers.

PMID- 19741998
TI  - Microwave-discharge excitation of an ArXe laser.

PMID- 19741999
TI  - Distinguishing molecular-reorientation gratings from thermal gratings by a time
      delayed method.

PMID- 19742000
TI  - Optical pulse compression using a TeO2 acousto-optical light deflector.

PMID- 19742001
TI  - Phase correction of femtosecond optical pulses using a combination of prisms and
      gratings.

PMID- 19742002
TI  - Cavity-length detuning effects and stabilization of a synchronously pumped
      femtosecond linear dye laser.

PMID- 19742003
TI  - Simultaneous formation of solitons and dispersive waves in a femtosecond ring dye
      laser.

PMID- 19742004
TI  - Nonlinear Schroedinger solitons in a periodic structure.

PMID- 19742005
TI  - Absorption and second-harmonic generation of monomer and aggregate hemicyanine
      dye in Langmuir-Blodgett films.

PMID- 19742006
TI  - Efficient blue emission from intracavity-doubled 946-nm Nd:YAG laser.

PMID- 19742007
TI  - Ultraviolet four-wave mixing phase conjugation with metastable color-center
      states in diamond.

PMID- 19742008
TI  - Thresholding semilinear phase-conjugate mirror.

PMID- 19742009
TI  - Exact solution of degenerate four-wave mixing in photorefractive media.

PMID- 19742010
TI  - Multigrating phase conjugation: exact results.

PMID- 19742011
TI  - Frequency-modulated to amplitude-modulated signal conversion in a Brillouin
      induced phase change in single-mode fibers.

PMID- 19742013
TI  - Wavelength-selective optical-fiber directional couplers using dispersive
      materials.

PMID- 19742012
TI  - Polarization-dependent pulse compression and broadening due to polarization
      dispersion in dispersion-shifted fiber.

PMID- 19742014
TI  - Weak coupling of parallel waveguides.

PMID- 19742016
TI  - Analysis of propagation characteristics of diffused channel waveguides: weighted
      residual method.

PMID- 19742015
TI  - Total absorption of unpolarized radiation by opaque layered media.

PMID- 19742017
TI  - Thermal tapering of ion-exchanged channel guides in glass.

PMID- 19742018
TI  - Low-loss high-extinction polarizers fabricated in LiNbO3 by proton exchange.

PMID- 19742019
TI  - Optical waveguides in oxygen-implanted buried-oxide silicon-on-insulator
      structures.

PMID- 19742020
TI  - Demonstration of a picosecond optical-phase conjugation-based residue-arithmetic
      computation.

PMID- 19742021
TI  - Arbitrarily high focal depth with finite apertures.
AB  - We modify the concept of superresolution for achieving arbitrarily extended focal
      depth with a finite aperture. The Legendre polynomials are used for designing a
      novel apodizer that produces arbitrarily high depth of focus. This kind of
      apodizer can also arbitrarily reduce the sensitivity to spherical aberration.
      Since these benefits are achieved at the expense of light throughput, we report
      on a formula for evaluating light throughput of this kind of filter.

PMID- 19742022
TI  - Eye-length measurement by interferometry with partially coherent light.
AB  - With a multimode semiconductor laser we have been able to measure the optical
      length of the eye within a precision of 0.03 mm. A first series of in vivo
      measurements acoustically determined eye length.

PMID- 19742023
TI  - Stratified volume holographic optical elements.
AB  - A computational algorithm for analyzing diffraction properties of optical
      devices, the optical beam propagation method, has suggested a new class of
      devices by which Bragg regime (thick grating) response can be obtained from a
      spaced sequence of thin grating layers. Such stratified volume holographic
      optical elements (SVHOE's) can emulate distributed volume gratings in terms of
      diffraction efficiency and angular selectivity and in addition possess periodic
      diffraction properties that might serve, for example, as interconnections for
      optical cellular logic arrays. SVHOE's also offer a unique capability for
      altering the device diffraction response on a layer-by-layer basis, allowing for
      control of both the diffraction peak width and the angular separation of adjacent
      peaks.

PMID- 19742024
TI  - Enhanced transmission in CO(2)-laser-aerosol interactions.
AB  - The transmission characteristics of a high-power CO(2)-laser beam through a
      single water aerosol particle are studied. It is found that before the onset of
      plasma formation there is a sizable range of laser intensity where the medium
      becomes almost totally transparent. A plausible argument for this induced
      transparency is given in terms of particle disintegration. This effect may have
      applications in laser atmospheric propagation.

PMID- 19742025
TI  - Proposed single-pulse two-dimensional temperature and density measurements of
      oxygen and air.
AB  - A combination of laser-induced fluorescence and Rayleigh scattering from an ArF
      laser tuned onto an oxygen transition is proposed for instantaneous two
      dimensional measurements of temperature and density. A model giving the
      temperature and frequency dependence of these mechanisms is developed, and
      supporting experimental results are presented.

PMID- 19742026
TI  - Simple method for identifying doubly ionized uranium (U III) produced in a hollow
      cathode discharge.
AB  - We have studied by emission spectroscopy the spectral properties of doubly
      ionized uranium, produced in a vapor generator of hollow-cathode design, as a
      function of the nature of a pure fill gas (helium, neon, argon, krypton, xenon)
      and its pressure. The spectral intensity is found to increase with increasing
      ionization potential of the discharge buffer gas, except in the case of helium.
      Based on our preliminary results, a simple and practical method for the positive
      identification of the complex U III spectrum is suggested.

PMID- 19742027
TI  - Unstable laser resonators with super-Gaussian mirrors.
AB  - A new class of tapered reflectivity mirrors with a super-Gaussian profile R
      infinity exp(-kr(n)) is introduced, and a geometrical-optics approach for
      analysis and design of unstable resonators made with these mirrors is presented.
      A super-Gaussian mirror, built by a special evaporation technique, has been
      tested in an unstable resonator of a pulsed Nd:YAG laser, demonstrating its
      effectiveness in generating diffraction-limited beams.

PMID- 19742028
TI  - Diode-laser-array-pumped neodymium slab oscillators.
AB  - A high-power multistripe diode-laser array has been used to pump miniature zigzag
      slab oscillators of Nd:YAG and Nd:glass. With Nd:YAG we have demonstrated output
      at 1.06 microm of 70-kW peak power and 585-mW average power with an electrical-to
      optical efficiency of 4%. In this experiment the Nd:glass lasers were limited to
      160-mW average power and less efficiency than the Nd:YAG. The differences between
      these materials are discussed.

PMID- 19742029
TI  - Laser action with (F(2)(+))(A) centers in additively colored lithium-doped KI.
AB  - Laser action has been achieved with lithium (F(2)(+))(A) centers in additively
      colored KI. In preliminary measurements, this material has been tuned
      continuously between 2.72 and 3.67 microm. The material was coaxially pumped with
      a pulsed 1.73-microm Er:YLF laser, and (F(2)(+))(A) centers were produced by
      using a selective, two-step photoionization technique, These additively colored
      crystals have the practical advantage of being reusable after cycling between
      liquid-nitrogen and room temperature.

PMID- 19742030
TI  - Nd:MgO:LiNbO(3) continuous-wave laser pumped by a laser diode.
AB  - Diode-pumped laser oscillation was achieved in Nd:MgO:LiNbO(3). The absorbed pump
      power thresholds were as low as 1.9 mW for the high-gain or pi polarization and 8
      mW for the low-gain polarization. A cw output power of 2 mW was obtained for the
      pi polarization at lambda = 1.085 microm for 9 mW of absorbed pump power. A slope
      efficiency of 37% was achieved. The diode-pumped Nd:MgO:LiNbO(3) lasers operated
      for extended periods of time without exhibiting any reduction in output power.

PMID- 19742032
TI  - Competition between stimulated three-photon scattering and parametric four-wave
      mixing.
AB  - We show that destructive interference between the polarizations produced by three
      photon scattering and parametric four-wave mixing suppresses the gain at the
      three-photon frequency under quite general conditions. The conditions for the
      suppression are discussed, and experimental verification in Na vapor is
      presented.

PMID- 19742031
TI  - Two-photon absorption and third-order nonlinearities in GaAs quantum dots.
AB  - Third-order optical nonlinearities of GaAs quantum dots are investigated
      theoretically. Two quantum confinement regimes are analyzed, and large optical
      nonlinearities are predicted for sufficiently narrow linewidths. The appearance
      of an induced (two-photon) absorption resonance is predicted energetically above
      the exciton resonance for quantum-dot radii, which are between the electron and
      hole Bohr radii.

PMID- 19742033
TI  - Absolute minimum instability thresholds in a nonlinear ring cavity containing a
      Kerr medium.
AB  - Stability analysis of an arbitrary-finesse ring cavity containing a Kerr medium
      of arbitrary response time reveals an absolute minimum threshold for the driving
      intensity necessary for realization of self-pulsing instabilities. This threshold
      is minimized not only with respect to cavity mistuning but also with respect to
      the medium's response time. The instability threshold is typically six times that
      for optical bistability.

PMID- 19742034
TI  - Coherent 70.9-nm radiation generated in neon by frequency tripling the fifth
      harmonic of a Nd:YAG laser.
AB  - We have produced coherent radiation in the XUV region at 70.9 nm by frequency
      tripling the fifth harmonic of Nd:YAG laser radiation in neon. BaB(2)O(4) was
      used to generate the fifth harmonic at 212.8 nm with an output pulse energy of 20
      mJ and a pulse width of 5 nsec. Subsequent frequency tripling in neon gas
      generated 10 W of peak power at 70.9 nm.

PMID- 19742035
TI  - Time-resolved buildup of a photorefractive grating induced in Bi(12)SiO(20) by
      picosecond light pulses.
AB  - Photorefractive gratings are induced with picosecond light pulses in a BSO
      crystal. Both experiment and calculations show a buildup of the effect governed
      by a diffusion of the excited charge carriers that occurs after illumination.

PMID- 19742036
TI  - High-contrast submilliwatt switches in an optically bistable liquid-crystal
      etalon utilizing absorption of reflected signal.
AB  - The demonstration of an all-optical bistable etalon utilizing absorption of the
      reflected signal is reported and theoretically justified.

PMID- 19742037
TI  - Wavelength- and polarization-selective fused single-mode couplers.
AB  - Analytical results are presented that describe the characteristics of fused
      single-mode tapered couplers. The influence of coupler geometry on polarization
      splitting and spectral selectivity is investigated. A selective fused coupler has
      been made that exhibits a channel separation of Deltalambda = 0.6 nm, an
      insertion loss of 1 dB, and an extinction ratio of 20 dB. Polarization
      selectivity of 20 dB has also been achieved.

PMID- 19742038
TI  - High-resolution and high-sensitivity optical-time-domain reflectometer.
AB  - We demonstrate a photon-counting optical-time-domain reflectometer (OTDR)
      operating at a wavelength of 0.85 microm at room temperature with high
      sensitivity (3 x 10(-15) W) at high resolution (1.5 cm, 150 psec). Measurements
      of splice losses and Rayleigh scattering losses less then 0.1 dB with centimeter
      resolution are demonstrated to be possible with such an OTDR.

PMID- 19742039
TI  - Fiber-optic passive ring-resonator gyroscope using an external-cavity laser
      diode.
AB  - We report a fiber-optic passive ring-resonator gyroscope that uses an external
      cavity laser diode. The external-cavity laser diode is useful as the light source
      for the gyroscope if an appropriate cavity length is chosen. A rotation detection
      sensitivity of 10(-2) rad/sec was obtained with an integration time of 10 sec.

PMID- 19742040
TI  - Linear phase detection for a bimodal fiber sensor.
AB  - Interference between the LP(01) and LP(02) modes is used to measure fiber
      elongation. We present a passive phase-detection technique that uses a mask in
      the far field of the output beam and spatial filters in the image of the fiber
      end face, giving a linear response. Experimental results show a precision of
      about 3% of one period, which corresponds to a 4-microm elongation.

PMID- 19742041
TI  - Double-polarization interferometer for digital force sensing by fiber tension
      bending.
AB  - A fiber-optic interferometric force sensor with digital readout by fringe
      counting is investigated. Ambiguity in fringe counting is eliminated by employing
      the double-polarization method. Force F(t), transverse to the fiber axis, is
      measured by tension-bending-induced fiber strain. A theoretical strain-force
      characteristic is derived, yielding an F(t)(2/3) dependence of fiber strain on
      the transverse force that is verified experimentally.

PMID- 19742042
TI  - Low-loss semiconductor waveguide bends.
AB  - An experimental comparison is made between the losses of waveguide bends in
      disorder-delineated waveguides in semiconductor superlattices composed of GaAs
      and AlAs layers for simple abrupt bends and abrupt bends with an additional half
      angle guiding wall proposed by Shiina et al. [Opt. Lett. 11, 736 (1986)]. For
      light above the band gap of bulk GaAs, the abrupt and Shiina bends were found to
      have to 3-dB loss angles of 3 and 7 deg, respectively. This improved performance
      suggests that the specific geometry of the bends is yet another degree of freedom
      in designing guiding structure for planar routing.

PMID- 19742043
TI  - Optical implementation of the Hopfield model for two-dimensional associative
      memory.
AB  - Optical implementation of Hopfield's neural network model [Proc. Natl. Acad. Sci.
      USA 79, 2554 (1982)] for two-dimensional associative memory is discussed. Two
      state neuron elements are represented by a twisted nematic liquid-crystal optical
      switch array, and three-dimensional holographic interconnections are realized
      with these elements. Unipolar connections, created by adding a constant to
      bipolar interconnections and compensating them with an input-dependent
      thresholding operation, are realized. The 16- (4 x 4) neuron system model acts as
      a content-addressable associative memory with error-correction capability.

PMID- 19742044
TI  - Phase-only modulation with twisted nematic liquid-crystal spatial light
      modulators.
AB  - It is shown that twisted nematic liquid-crystal spatial light modulators behave
      as phase-only modulators when operated below the conventional optical threshold.
      Thus such devices, when operated in a reflection mode, behave as spatial
      amplitude modulators when used between crossed polarizers above the optical
      threshold; they behave as phase modulators when used between parallel polarizers
      and operated below that threshold.

PMID- 19742045
TI  - Biphotonic process for recording holograms with continuous-wave lasers in the
      near infrared: erratum.

PMID- 19742046
TI  - Statistical distribution of frequency fluctuations in semiconductor lasers:
      erratum.

PMID- 19742047
TI  - Are fear-avoidance beliefs in low back pain patients a risk factor for low
      physical activity or vice versa? A cross-lagged panel analysis.
AB  - OBJECTIVE: The assumption that low back pain (LBP) patients suffer from "disuse"
      as a consequence of high fear-avoidance beliefs is currently under debate. A
      secondary analysis served to investigate whether fear-avoidance beliefs are
      associated cross-sectionally and longitudinally with the physical activity level
      (PAL) in LBP patients. METHODS: A total of 787 individuals (57% acute and 43%
      chronic LBP) were followed up over a period of one year with measurements of fear
      avoidance beliefs and physical activity level. Fear-avoidance beliefs concerning
      physical activity were measured by the physical-activity subscale of the FABQ
      (Fear-Avoidance Beliefs Questionnaire), the physical activity level was assessed
      in weighted metabolic equivalents (MET) hours/week with a German self-report
      questionnaire. Data were investigated by structural equation modelling in a cross
      lagged panel design for the whole sample and separately for acute and chronic
      LBP. RESULTS: The acute and chronic sub sample increased their total physical
      activity level significantly after one year. The structural equation modelling
      results did not support the disuse-aspect inherent in the fear-avoidance belief
      model. Cross-lagged path coefficients were low (.04 and .05 respectively) and,
      therefore, did not allow to predict final physical activity by initial fear
      avoidance beliefs or vice versa. DISCUSSION: Consequently, due to missing links
      between fear-avoidance beliefs and physical activity in a longitudinal design,
      the assumptions of the fear-avoidance belief model have to be questioned. These
      findings are in line with other investigations published recently. Most probably,
      "fear-avoidance belief" represents a cognitive scheme that does not limit
      activity per se, but only is directed to the avoidance of specific movements.

PMID- 19742048
TI  - Screening for Generalized Anxiety Disorder in inpatient psychosomatic
      rehabilitation: pathological worry and the impact of depressive symptoms.
AB  - OBJECTIVE: Pathological worry is considered to be a defining feature for
      Generalized Anxiety Disorder (GAD). The Penn State Worry Questionnaire (PSWQ) is
      an instrument for assessing pathological worry. Two earlier studies demonstrated
      the suitability of the PSWQ as screening instrument for GAD in outpatient and non
      clinical samples. This study examined the suitability of the PSWQ as a screening
      instrument for GAD in a German inpatient sample (N=237). Furthermore, a
      comparison of patients with GAD and patients with depression and other anxiety
      disorders regarding pathological worry and depression was carried out in a sub
      sample of N=118 patients. METHOD: Cut-off scores optimizing sensitivity,
      optimizing specificity and simultaneously optimizing both sensitivity and
      specificity were calculated for the PSWQ score by receiver operating
      characteristic analysis (ROC). Differences regarding pathological worry and
      depression measured by the PSWQ and the Beck Depression Inventory (BDI) across
      five diagnostic subgroups were examined by conducting one-way ANOVAs. The
      influence of depression on pathological worry was controlled by conducting an
      ANCOVA with BDI score as a covariate. RESULTS: The ROC analysis showed an area
      under the curve of AUC=.67 (p=0.02) with only 54.4% of the patients correctly
      classified. Comparison of diagnostic subgroups showed that after controlling the
      influence of depression, differences referring to pathological worry between
      diagnostic subgroups no longer existed. CONCLUSIONS: Contrary to the earlier
      results we found that the use of the PSWQ as a screening instrument for GAD at
      least in a sample of psychotherapy inpatients is not meaningful. Instead of that,
      the PSWQ can be used to discriminate high from low worriers in clinical samples.
      Thus, the instrument can be useful in establishing e.g. symptom-oriented group
      interventions as they are established in behavioural-medicine inpatient settings.
      Furthermore, our findings stress the influence of (comorbid) depressive symptoms
      on the process of worrying.

PMID- 19742049
TI  - Validation and reliability of the German version of the Chronic Pain Grade
      questionnaire in primary care back pain patients.
AB  - In 1992 Von Korff and his co-workers developed a simple, brief questionnaire to
      assess the severity of chronic pain problems, the Chronic Pain Grade (CPG). The
      present study was conducted to analyse the psychometric properties of the
      translated German version of the CPG within a population of primary care back
      pain patients (n=130). Factor analysis yielded two factors which accounted for
      72% of the variance of the questionnaire. The first factor 'Disability Score'
      (53.56% of the variance) revealed a good internal consistency (alpha=.88), the
      internal consistency of the second factor 'Characteristic Pain Intensity' was
      moderate (alpha=.68). The reliability of the whole instrument was good
      (alpha=.82). The CPG and its subscales show moderate to high relations with other
      instruments assessing the patient's disability (FFbH-R, Pain Disability Index
      PDI). Additionally weak to moderate but significant correlations were found
      between the CPG and other measures of grading and staging chronic pain (MPSS,
      RGS). Further, positive correlations between the CPG and both, the frequency of
      doctor visits and the frequent use of pain medication have been seen. The
      reported findings suggest, that the German version of the CPG is a reliable,
      valid and useful instrument if a brief, simple method of grading the severity of
      chronic pain is needed. The German version leads to a better comparability
      between German and English language studies and facilitates an international
      collaboration in this field of research.

PMID- 19742050
TI  - Neural processing of traumatic events in subjects suffering PTSD - a case study
      of two surgical patients with severe accident trauma.
AB  - Neuroimaging research on the neurobiology of chronic PTSD (posttraumatic stress
      disorder) has revealed structural and functional alterations primarily affecting
      areas of the medial temporal lobe (hippocampus, amygdala, and parahippocampal
      gyrus) and the frontal cortex known to be associated with the disorder. Using
      functional magnetic resonance imaging (fMRI), the present study studied the
      functional neuroanatomy of traumatic and non-traumatic emotional memory in two
      surgical patients who had sustained severe accident trauma. While patient 1 had
      developed acute PTSD following the traumatic event, patient 2 (control) did not.
      When confronted with traumatic (relative to negatively valenced non-traumatic)
      memory, the PTSD patient exhibited evidence for increased neural activity in the
      right and the left superior temporal lobe, the amygdala, the left angular gyrus,
      and the medial frontal gyrus, while the non-PTSD patient exposed to identical
      conditions showed increased activations in frontal and parietal regions. Both
      patients exhibited identical activation patterns when recalling non-traumatic
      memories relative to neutral memories. It is concluded that the pronounced
      activation patterns in the PTSD patient may be considered specific for acute
      PTSD, involved with the emotional arousal and the vivid visual recollections
      typical for the acute phase of the disorder.

PMID- 19742051
TI  - Predictive value of breast cancer cognitions and attitudes toward genetic testing
      on women's interest in genetic testing for breast cancer risk.
AB  - In the past years advances in genetic technologies have led to an increased
      interest in predictive genetic testing for breast cancer risk. Studies in the US
      and UK reported an increasing interest among women of the general public in
      genetic testing for breast cancer risk, although the benefit of such a test is
      questionable for low risk women. The aim of the present study was to identify
      factors that predict interest in genetic testing of German women in the general
      public. Women with neither a family history of breast cancer nor breast cancer
      themselves received an information letter by mail, were interviewed by telephone,
      and completed a self-administered questionnaire (N=377). Structural equation
      modeling was used to determine the predictive value of attitudinal and cognitive
      variables on interest in genetic testing for breast cancer risk. The resulting
      model achieved good fit indices, and 42% of variance could be explained. Women
      with more expectations concerning the test, more positive attitudes concerning
      genetic testing in general, an increased breast cancer risk perception, and
      increased breast cancer worries showed more interest in testing. These findings
      suggest the need for information and counseling strategies for low risk women
      which should focus in particular on decreasing unrealistic expectations
      concerning genetic testing for breast cancer risk but also on decreasing
      perceived breast cancer risk and breast cancer worries.

PMID- 19742052
TI  - Psycho-Social-Medicine - More than just another journal.

PMID- 19742053
TI  - The development of guidelines for the treatment of patients with mental disorders
      under particular consideration of rehabilitative aspects.
AB  - Inpatient psychotherapeutic treatment is quite extensive in Germany. Three
      treatment systems (psychosomatic/psychotherapeutic healthcare,
      psychiatric/psychotherapeutic healthcare and rehabilitation of patients with
      mental disorders) exist relatively independently from one another. They show
      large areas of overlap, however, with regard to various criteria. This is due to
      the fact that, as opposed to many somatic illnesses, a clear distinction between
      acute-medical and rehabilitative elements cannot be made in the treatment of
      mental disorders.Systematic treatment recommendations in the form of guidelines
      could aid in determining the optimal treatment form for patients.The current
      development of guidelines for mental disorders will thus be presented and
      analyzed in this article. Particular focus will be placed on rehabilitative
      aspects. The presentation and analysis will take place using the example of
      guidelines written for panic disorders. Based on a national and international
      investigation of guidelines (internet, databases) 11 guidelines for panic
      disorder (2 German guidelines, 9 from English spoken countries; target group of 9
      guidelines: general practitioners; recommendations concerning diagnostics
      /assessment and treatment) were analysed. The results demonstrate a considerable
      need for development as rehabilitative elements are only marginally mentioned in
      the guidelines up to now. Of the 16 rehabilitative elements being investigated,
      only two ("psycho education" and "pharmacotherapy of chronic illness in the long
      term perspective") are considered more than once in the guidelines. Seven
      elements (e.g. "salutogenic aspects of the therapy/ measures for the maintenance
      of quality of life", "methods of long-term guidance") are not mentioned at all.
      Based on the results of the analyses performed, conclusions for the further
      development of guidelines will be presented for discussion.

PMID- 19742054
TI  - Age and sex dependencies of anxiety and depression in cardiologic patients
      compared with the general population.
AB  - OBJECTIVE: The aim of this study was to test age and sex effects on anxiety and
      depression using the Hospital Anxiety and Depression Scale HADS. METHOD: Sample 1
      consisted of 2037 subjects of the German general population, and sample 2
      comprised 2696 cardiologic patients. RESULTS: In the group of the general
      population we observed a linear increase of depression and (to a lower extent) of
      anxiety with age. In contrast to that, the patients reached their anxiety and
      depression maxima in the range of 50 to 60 years, with decreasing mean values for
      older patients. This effect was observed in both sexes and was proved by an ANOVA
      interaction between age category and population (P<0.001). In the age range over
      70 years the mean depression scores of the patients were even lower than those of
      the general population. Especially high anxiety and depression scores were found
      for retired males under 60 years of age. CONCLUSION: Premature retirement is
      associated with anxiety and depression in cardiologic patients which partly
      accounts for the different age effects of the samples. Longitudinal studies are
      needed to explain the underlying mechanisms of the age effects in more detail.

PMID- 19742055
TI  - Career support in medicine - experiences with a mentoring program for junior
      physicians at a university hospital.
AB  - PURPOSE: Until now, mentoring has hardly been used by the medical profession in
      German-speaking countries as a means of supporting junior physicians in their
      careers. The aim of the mentoring project described here was to obtain
      information for promoting and developing future mentoring programs at a
      university hospital. METHOD: A new integrated mentoring model was developed and
      implemented over a 12-month period. Peer groups were advised on the mentoring
      process by mentors and program managers. A total of eight mentoring groups (40
      peers) from four departments of a university hospital took part in the project:
      four voluntarily, and four on a compulsory basis. The evaluation was carried out
      using qualitative methods for analysis of the group protocols and the focus group
      interviews with the participants. RESULTS: Group discussions revealed that
      individual mentees, young female physicians in particular, developed concrete
      career plans and initiated further career-relevant steps. Some mentees - again
      more women than men - were promoted to senior physician posts. Further measurable
      career steps were increased research and publishing activity, and research
      fellowships abroad. The group process developed in five typical phases (forming,
      storming, norming, performing, and finalizing), which differed according to
      whether the groups had been formed on a voluntary or compulsory basis. In the
      evaluation interviews, mentees emphasized the following as effective mentoring
      factors: Concrete definition of own career goals; exchange of experiences within
      the peer groups; support and motivation from the mentors; and fostering of the
      group process by the program managers. CONCLUSION: Participation in mentoring
      programs has to be voluntary. Mentees are motivated, autonomous, goal-oriented
      and prepared to take action. Mentors serve as examples and advisers. They derive
      satisfaction from being held in high esteem, as well as from the advancement of
      their own careers. Program managers have experience in systems theory and group
      dynamics, structure the group processes, and evaluate the quality of the results.
      Hospital management should regard mentoring as a business strategy and a means of
      staff development and quality management, and provide the necessary resources.
      The mentoring program presented here is being extended to other departments of
      the hospital on the basis of the positive experiences it has offered.

PMID- 19742056
TI  - Work and health conditions of nursing staff in palliative care and hospices in
      Germany.
AB  - Aims of this representative study were to assess the relevant differences between
      the work and organisational characteristics as well as the subjective resources
      and health status of nurses occupied in hospice care, compared to nurses from
      palliative stations. Further, the assessment of the predictive correlations
      between the work situation of this nurses as a factor influencing their health
      and perceived strains was also a leading intention. METHOD: In a written survey
      conducted in Germany in 2001, 820 nursing staff of 113 palliative stations and
      stationary hospices were included. A qualified diagnostic procedure for the
      assessment of health promoting work was implemented. In order of obtaining a
      secure comparison, a sample of 320 nurses working in 12 homes for old people in
      Saxony was also considered. RESULTS: The nurses referred generally to favourable
      working conditions, still they informed about deficiencies in the perceived
      participation, organizational benefits and experienced gratification. Hospice
      nurses experienced overall more favourable work conditions than palliative nurses
      or than the staff of homes for old people (regarding identification with the
      institution, organizational benefits, accurate gratification and little time
      pressure during work). Hospice personnel were psychologically and physically
      healthier than the staff of palliative stations. Important predictors for health
      stability that could be assessed by multiple regression analysis were: positively
      evaluated work contents, the identification with the institution, little time
      pressure and a positive working atmosphere. CONCLUSIONS: The assessed
      organisational framework is generally more favourable in the institutions of
      professional terminal care than in common hospitals and homes for old people.
      Therefore, the conditions in hospices could have a modelling function for the
      inner-institutional work organisation and for the anchorage of the intrinsic
      motivation of nurses in the health care system.

PMID- 19742057
TI  - Internal psychosomatic medicine within the German Diagnosis Related Groups
      System.
AB  - A model calculation was used to assess whether the G-DRG version 1.0 sufficiently
      represents integrated internal psychosomatic treatment of patients with
      psychosomatic disorders in relation to diagnosis and resource consumption. The
      DRGs of the Major Diagnostic Category "Mental Diseases" of the German DRG
      calculation sample 1.0 (diagnoses, procedures, cost weights) were analyzed. In a
      division of psychosomatic medicine within a general internal department, proceeds
      regarding 241 patients treated between 01 Jan and 31 Dec 2002, calculated
      according to the G-DRG version 1.0, were compared to the costs accrued. The G-DRG
      version 1.0 includes 7 DRGs of psychosomatic disorders in internal medicine
      (excluding disorders due to substance abuse). Assuming a base rate of euro 2,900,
      the total proceeds of the G-DRG Version 1.0 exceeded the costs (+ euro 57,971
      /year).

PMID- 19742058
TI  - Personality, illness perceptions, and lung function (FEV1) in 50 patients after
      lung transplantation.
AB  - OBJECTIVE: After lung transplantation little attention has been devoted to
      patient's personality and illness perceptions, although the importance of illness
      perceptions (e.g. to the psychosocial status of health) as well as the
      relationship between personality and illness perceptions is well-known from other
      areas of medicine. METHODS: Fifty patients more than one year after lung
      transplantation were surveyed by the NEO Five-Factor Inventory (NEO-FFI) as well
      as the "control" and "consequences" scales of the Illness Perception
      Questionnaire (IPQ). Medical data included the diagnoses of the underlying lung
      diseases and the pulmonary graft function as measured by the forced expiratory
      volume in one second (FEV(1)). RESULTS: In our patients, mean values of the
      personality factors "extraversion" (p=.003), "openness to experiences" (p<.001),
      "agreeableness" (p=.035), and "conscientiousness" (p<.001) were significantly
      higher compared to the normal population. "Openness to experiences" correlated
      positively and "neuroticism" negatively with the illness perception "control".
      There was no correlation between illness perceptions and lung function.
      CONCLUSION: In lung transplant recipients, personality traits are more relevant
      to illness perceptions ("control") than current graft function.

PMID- 19742059
TI  - Differences in body image between anorexics and in-vitro-fertilization patients -
      a study with Body Grid.
AB  - OBJECTIVES: The purpose of the investigation was to explore the body image
      disturbance of anorexics and in-vitro-fertilization patients (IvF-patients) with
      Body Grid and Body Identity Plot. METHODS: The paper reports on an empirical
      study conducted with 32 anorexic patients and 30 IvF-patients. The structure of
      the body image was derived from the Body Grid, an idiographic approach following
      the Role Repertory Grid developed by George A. Kelly [17]. The representation of
      the body image and the degree of body-acceptance is represented graphically.
      RESULTS: By the Body Grid and Body Identity Plot measures we were able to
      identify important differences in body image between anorexics and IvF-patients.
      CONCLUSION: The tendencies of dissociation in the body image of anorexics which
      we found must be seen in the sense of a specific body image disturbance which
      differs significantly from the body-experience profile of IvF-patients. With the
      grid approach it was possible to elicit the inner structure of body image and
      determine the acceptance of the body and integration of single body parts.

PMID- 19742060
TI  - Between professional autonomy and economic orientation - The medical profession
      in a changing health care system.
AB  - The current discussions surrounding the German health care system are being
      determined and defined by the concepts of "profitability", "efficiency" and
      "saving". These concepts also determine the demands made on this system and have
      had an effect on the medical profession. The economy's growing influence on
      physicians' decision-making and the increasing necessity to look at and regulate
      services under economic aspects arising from the need to save costs are seen by
      the medical profession as a threat to its autonomous conduct and freedom to make
      decisions, in other words it sees it as a danger to its medical orientation.
      Conflicts between medical autonomy and economic orientation in physicians'
      conduct are therefore already foreseeable, as are conflicts between medicine and
      economy in regards to who has the power to define the terms of the public health
      system. OBJECTIVE: This article will outline the area of conflict based on the
      available literature. It will discuss how the political and economic regulatory
      attempts affect the medical profession's autonomous conduct. It will also discuss
      which conflicts of conduct emerge for physicians, what types of solutions the
      medical profession tends to develop as a reaction, and whether or not this
      tension between medical and economic orientation can be resolved in an acceptable
      way. METHODOLOGY: This article should first outline the changed economic and
      political basic conditions and the attempts to reform the German health care
      system, using this as a starting point. Following this, it will explore the
      significance professional autonomy acquires within the concept of profession from
      the point of view of the sociology of professions. With this in mind, the third
      part of this article will describe and analyze the effects of advanced
      economization on the medical profession's autonomous conduct, which has long been
      regarded as uncontested. This part of the article will also describe and analyze
      the medical profession's strategies it uses to defend its autonomy. Finally, this
      article will discuss whether or not a stronger integration of medical and
      economic responsibility is possible. Conclusion and summary: The conclusion that
      will be drawn from this discussion is that the medical profession can only avoid
      the pending loss of its autonomy (deprofessionalization) if it is able to combine
      cost efficiency and quality (and integrate economic aspects into its actions). If
      it is unable to do so, it will lose more and more control over the public health
      system to the state, economy, and management.

PMID- 19742061
TI  - Social capital and self-rated health in 21 European countries.
AB  - STUDY OBJECTIVE: The aim of this paper is to explore the association between
      social capital and self-rated health in different European countries. METHODS:
      For the cross sectional, comparative analyses data from 21 European countries
      were used. 40,856 people aged 15 years and older were personally interviewed in
      2003 (European Social Survey). Perceptions of social trust, and membership,
      participation and voluntary work in civic organisations were used as social
      capital indicators. Analyses are conducted on an aggregate level (country) and on
      an individual level. MAIN RESULTS: Results indicate comparatively low levels of
      social capital in East and South European countries. Countries with low levels of
      social capital have a high percentage of residents reporting poor health. Social
      capital is significantly associated with self-rated health in most of the
      European countries on the individual level after accounting for gender and age.
      However, additional adjustment for socio-economic status results in a decrease of
      the associations between activities in voluntary organisations and health.
      Further adjustment for social contacts and emotional support results in only
      minor changes of the associations. CONCLUSIONS: Analyses reveal strong
      correlations between social capital and self-rated health in a number of European
      countries on the aggregate level. Associations on the individual level are weaker
      in East and South European countries. Moreover, association of self-rated health
      with perceptions of social trust seems to be more consistent than with activities
      in voluntary organisations.

PMID- 19742062
TI  - Inpatient psychotherapeutic treatment for cardiac patients with depression in
      Germany - short term results.
AB  - The purpose of the PROTeCD(Psychotherapeutic Resource-Orientated Treatment for
      Cardiac Patients with Depression)-study was to develop and to evaluate a brief
      psychotherapeutic intervention for rehabilitation in-patients with coronary heart
      disease (CHD) and depressive disorders. In three cardiac rehabilitation hospitals
      all patients were screened for mental distress at admission. Patients generally
      stay for 3 to 4 weeks before being referred to outpatient care. METHOD: Those
      patients with elevated distress were interviewed for mental disorders and took
      part in the baseline-assessment. Patients diagnosed with a depressive disorder at
      baseline were randomised into the intervention or the usual care group. Efficacy
      was assessed at discharge from hospital (short-term). 59 subjects with CHD and co
      morbid depressive disorder were randomised into the trial - 27 into the
      intervention group (IG) and 32 into the usual care group (UC). Patients in the
      intervention group received 4 to 6 individual psychotherapeutic sessions of 50
      minutes each, including patient education and cognitive-behavioural treatment of
      depression. Outcome measures were depressive and anxiety symptoms in self report
      and interview. RESULTS: There was no significant difference between intervention
      and usual care group in this short-term reduction of depressive symptoms, mental
      distress and anxiety. However, at discharge the patients still suffer from an
      increased level of distress compared to the recommended cut off scores of the
      assessment scales. CONCLUSION: Multimodal inpatient rehabilitation reduces
      depressive and anxiety symptoms in depressed CHD patients in short term
      independently of an additional psychotherapeutic intervention.

PMID- 19742063
TI  - The psychosocial evaluation of medically-ill inpatients - accordance between
      mental disorders and self-rated psychosocial distress.
AB  - BACKGROUND: Both psychometric questionnaires and structured psychodiagnostic
      interviews are used to identify medically-ill inpatients requiring
      psychotherapeutic treatment. The study examines the accordance between the
      diagnosis of a mental disorder (ICD-10) and self-rated psychosocial distress of
      unselected inpatients within the framework of a psychosomatic liaison service.
      METHODS: Of n=532 consecutive patients hospitalized in five departments of the
      University Hospital Freiburg, n=357 patients underwent a structured
      psychodiagnostic interview (Mini-DIPS) to obtain diagnoses according to ICD-10 F.
      Psychosocial distress (HADS), somatoform symptoms (SOMS-2 J), quality of life
      (EDLQ) and coping strategies (FQCI) were evaluated by self-rating questionnaires.
      RESULTS: A mental disorder requiring treatment was diagnosed in 44% of the
      patients. Predictors for the diagnosis of a mental disorder were the depression
      subscale of the HADS, the frequency of somatoform symptoms and depressive coping.
      The greatest accordance between mental disorders and screening instruments was
      found for the depression subscale of the HADS at a cut-off 8+. The area under the
      curve (AUC) was 0.75. With a specificity of 87% and a sensitivity of 53%, nearly
      half of all mental disorders requiring treatment were not identified by the HADS,
      especially in patients with neurotic, stress-related and somatoform disorders
      (F4), most of them cancer patients with adjustment disorders. CONCLUSIONS: Case
      selection by the HADS is successfull in disorders, where depressive symptoms are
      prevalent. For F4-diagnoses a lower cut-off of 6+ is recommended. The importance
      of a clinical interview is underlined. Other screening procedures, specific for
      the general hospital population, are discussed.

PMID- 19742064
TI  - Prevalence of somatoform pain complaints in the German population.
AB  - The prevalence of somatoform pain complaints was assessed in a representative
      sample of 2050 persons in Germany in the age range from 18 to 92 years by the
      Screening for Somatoform Symptoms questionnaire [57]. A high percentage of the
      study participants turned out to complain of serious somatoform pains. Most
      frequently, back pain (30.5%), joint pain, pain in the arms and/or legs (19.9%)
      and headache or facial pain (19.5%) were reported. Women complained of more
      somatoform pain symptoms than men. Pain was higher with an increasing age, lower
      education, lower income, rural residency, and residency in Eastern Germany. While
      the prevalence of somatoform pain is high, the majority of patients does not
      receive adequate psychotherapeutic care but is inadequately treated by somatic
      treatments.

PMID- 19742065
TI  - Biopsychosocial predictors of fatigue in quiescent and mild ulcerative colitis -
      an explorative study.
AB  - In 37 patients with ulcerative colitis (UC) and ileal pouch-anal anastomosis
      (IPAA) and 40 patients without IPAA fatigue was measured using the Short Form
      Giessen Subjective Complaints List GBB 24. Age, sex, disease activity (measured
      by the Colitis Activity Index CAI or the Pouch Disease Activity Index PDAI) and
      depressiveness (measured by the Hospital Anxiety and Depression Scale or the
      Center for Epidemiological Studies Depression Scale), active medical
      comorbidities and therapy by corticosteroids were tested for their predictive
      capacity regarding fatigue. One third of the patients indicated fatigue scores
      above the 95th percentile of the score of the general German population. The
      amount of fatigue in patients without IPAA was best predicted by the degree of
      depressiveness (corrected R(2)=0.30, beta=0.57, p<0.001). The amount of fatigue
      in patients with IPAA was best predicted by the PDAI-score (corrected R(2)=0.20,
      beta=1.35, p=0.03).

PMID- 19742066
TI  - A multivariate time-series approach to marital interaction.
AB  - Time-series analysis (TSA) is frequently used in order to clarify complex
      structures of mutually interacting panel data. The method helps in understanding
      how the course of a dependent variable is predicted by independent time-series
      with no time lag, as well as by previous observations of that dependent variable
      (autocorrelation) and of independent variables (cross-correlation).The study
      analyzes the marital interaction of a married couple under clinical conditions
      over a period of 144 days by means of TSA. The data were collected within a
      course of couple therapy. The male partner was affected by a severe condition of
      atopic dermatitis and the woman suffered from bulimia nervosa.Each of the
      partners completed a mood questionnaire and a body symptom checklist. After the
      determination of auto- and cross-correlations between and within the parallel
      data sets, multivariate time-series models were specified. Mutual and individual
      patterns of emotional reactions explained 14% (skin) and 33% (bulimia) of the
      total variance in both dependent variables (adj. R(2), p<0.0001 for the
      multivariate models).The question was discussed whether multivariate TSA-models
      represent a suitable approach to the empirical exploration of clinical marital
      interaction.

PMID- 19742067
TI  - On psychobiology in psychoanalysis - salivary cortisol and secretory IgA as
      psychoanalytic process parameters.
AB  - This study investigates the psychobiological impact of psychoanalysis in its four
      hour setting. During a period of five weeks, 20 subsequent hours of
      psychoanalysis were evaluated, involving two patients and their analysts. Before
      and after each session, saliva samples were taken and analysed for cortisol
      (sCortisol) and secretory immunoglobuline A (sIgA). Four time-series (n=80
      observations) resulted and were evaluated by "Pooled Time Series Analysis" (PTSA)
      for significant level changes and setting-mediated rhythms. Over all sessions,
      sCortisol levels were reduced and sIgA secretion augmented parallel to the
      analytic work. In one analytic dyad a significant rhythm within the four-hour
      setting was observed with an increase of sCortisol in sessions 2 and 3 of the
      week. Psychoanalysis may, therefore, have some psychobiological impact on
      patients and analysts alike and may modulate immunological and endocrinological
      processes.

PMID- 19742068
TI  - Posttraumatic stress disorders and extent of psychosocial impairments five years
      after a traffic accident.
AB  - This five year long-term follow-up study estimated the prevalence of
      Posttraumatic Stress Disorder (PTSD) and other mental health problems in traffic
      accident victims. 70 patients were invited for a personal interview to assess
      mental disorders (DIA-X), depression (BDI), mental distress (SCL-90-R), and
      psychosocial (SDS) and physical impairments at least five years after their first
      admission to a university hospital (Department of Traumatology). Prevalence of
      PTSD was 10%, and another 14.2% of the patients also had a partial PTSD. Other
      mental disorders had a lower prevalence (7.2%). Patients with PTSD did not differ
      in sociodemographic characteristics from patients without PTSD. PTSD patients
      were more depressed and showed more general psychological distress. Furthermore,
      PTSD was associated with impairments in job, social interaction, and leisure
      activities. Persistent medical and mental problems correlated highly with PTSD.
      Implications for secondary prevention of persistent mental health problems of
      traffic accident patients are discussed in their connection with PTSD.

PMID- 19742069
TI  - Health effects of expressive writing on stressful or traumatic experiences - a
      meta-analysis.
AB  - In his theory of emotional inhibition Pennebaker [44] proclaimed that the
      disclosure of stressful or traumatic experiences reduces the probability of
      detrimental health effects. In his experimental paradigm disclosure was induced
      by asking the participants to write about their deepest thoughts and feelings
      relating to a stressful event during 3 to 4 writing sessions of 15 to 20 minutes.
      Based on a meta-analysis of 13 studies Smyth [58] reported an average effect size
      of d=0.47 for various health related variables. Considering the great number of
      studies published since then, the aim of our study was to update the state of
      evidence regarding the effects of expressive writing on health, including only
      randomized controlled trials in our analysis. From 42 trials fulfilling the
      inclusion criteria 30 could be used for the meta-analysis. Neither regarding
      somatic nor psychological health variables significant effect sizes were found.
      Various exploratory analyses (e.g. restriction to clinical samples) also resulted
      in non-significant effect sizes, except for one rendering a very small effect
      size. Results of our meta-analysis lead to the conclusion that expressive writing
      has minor or no effects on the subject's health contrary to earlier findings.

PMID- 19742070
TI  - Temperament and personality: the German version of the Adult Temperament
      Questionnaire (ATQ).
AB  - The psychobiological orientation inherent in temperament concepts permits a close
      tie between temperament and the rapidly proliferating research areas of
      neurosciences and behavioural genetics. Based on developmental and
      psychobiological studies, the Adult Temperament Questionnaire (ATQ) by Rothbart
      measures self-regulatory processes in addition to constitutionally based
      individual reactivity. The purpose of this paper is to validate a German version
      of the short form of the ATQ with 77 items. 213 psychosomatic inpatients and
      outpatients and 116 control subjects took part in this study. The study included
      standardized measures of personality and symptoms. The German version reliably
      measures the four dimensions negative affect, extraversion, orienting sensitivity
      and effortful control; subscales were moderately correlated. We found a
      consistent pattern of correlation to personality (NEO-FFI) and interpersonal
      problems (IIP), negative affect strongly correlated with neuroticism; effortful
      control correlated with conscientiousness, orienting sensitivity with openness,
      and extraversion correlated with the corresponding scale of the NEO-FFI.
      According to our hypothesis, negative affect was positively correlated with
      higher distress and physical complaints, while effortful control was negatively
      correlated with them. When negative affect and effortful control were combined,
      effortful control had a moderating effect on distress. Clinical and non-clinical
      samples differed significantly on all dimensions; the ATQ appears to be suitable
      for differentiating subgroups of patients according to self-regulation.

PMID- 19742071
TI  - Worrying about one's job, family, financial situation and health - results of a
      population-representative study.
AB  - OBJECTIVE: Worrying about one's job, family, financial situation and health is
      distressing. How intense are these worries in the general population? METHODS: An
      inquiry representative of the German population (N=2473, age>14 years) was
      performed. The total score of the "Questionnaire for Assessing Subjective
      Physical Well-Being" (FEW) and the screening scale of the "Trier Inventory for
      the Assessment of Chronic Stress" (TICS) were correlated with the four above
      mentioned items addressing worries (range 1-4). RESULTS: Worries about one's
      financial situation were scored highest (mean=2.04, SD=0.92), followed by worries
      about one's health (mean=1.94; SD=0.87), one's family (mean=1.85; SD=0.86) and
      worries about one's job (mean=1.69; SD=0.92). Health worries increased with age.
      Those without a job and single parents showed the highest grades of solicitude.
      Increasing income decreased worrying. The correlations with chronic stress were
      moderate (.24<r<.33). The most significant correlation could be found between
      worries about one's health and the total score of the FEW (r=-.52). CONCLUSIONS:
      The general population's concerns are relatively low. Using normative data,
      people can be screened for psychosocial distress and possibly referred to a
      relevant form of psychosocial support.

PMID- 19742072
TI  - Measuring psychological stress and strain at work - Evaluation of the COPSOQ
      Questionnaire in Germany.
AB  - The undisputed increase of the relevance of mental work load is confronted with a
      lack of qualified or at least well documented measuring instruments covering all
      important aspects.The COPSOQ (Copenhagen Psychosocial Questionnaire), a
      comprehensive instrument for the assessment of psychosocial factors at work, was
      tested in a partly modified version in a large German sample (N = 2561
      employees). The aims of the study were the detailed investigation of the
      psychometric measurement properties, and based on these results, the development
      of an abbreviated version of the instrument.The analysis of objectivity,
      acceptance, practicability, sensitivity and content validity of the questionnaire
      as a whole did not show any problematic results - with some limitations regarding
      the length of the questionnaire.The assessment of the reliability,
      generalisability, construct validity, criterion validity and diagnostic power of
      the single scales showed medium to good measuring qualities for the majority of
      the scales (i.e. Cronbach's alpha mostly >0.7). In addition, the psychometric
      properties were very similar to those in the Danish COPSOQ-study.Considering all
      aspects of the measurement quality, a shortened version of the instrument was
      created. It attempts to combine measuring qualities as high as possible with a
      number of questions as low as possible.The German COPSOQ questionnaire is a free
      screening-instrument for the recording of psychosocial work load and strain for
      all enterprises and organisations interested. The next step is the construction
      of a "job exposure matrix" for psychosocial factors at work, that means a central
      database with work load profiles and reference values for as many occupational
      groups as possible.

PMID- 19742073
TI  - Mental adjustment to cancer and survival of patients admitted for allogenic
      hemopoietic stem cell transplantation - a prospective cohort study.
AB  - OBJECTIVE: The Mental Adjustment to Cancer Scale (MAC scale) has evolved to a
      standard measure in the field of psycho-oncology. In this context an attitude
      called "fighting spirit" gained much attention as a coping style. Some reports
      suggest that coping efforts as measured by the MAC scale are predictive for
      survival of breast cancer patients. We explored the predictive power of the MAC
      scale by using a sample of patients with haematological malignancies undergoing
      allogenic hemopoietic stem cell transplantation (HSCT). METHODS: Between 9/1999
      and 12/2001 127 patients were administered the MAC scale prior to HSCT. Follow-up
      data of overall survival and event-free survival were obtained in December 2003
      and analyzed using Cox-regression models. RESULTS: At the time of the follow-up,
      68 patients had died (overall survival), 75 patients had experienced a relapse or
      had died (event-free survival). We failed to find significant results for the MAC
      subscales with and without adjustment for prognostic factors. CONCLUSION: In the
      special situation of patients facing HSCT the MAC scale seems not to be of
      predictive value. In general, with respect to survival the empirical evidence is
      not very convincing.

PMID- 19742074
TI  - Health-related quality of life instruments and individual diagnosis - a new area
      of application.
AB  - OBJECTIVES: Various health-related quality of life (HRQoL) instruments for
      children and adolescents have been developed and are applied in clinical and
      health economic studies with the research focus on the HRQoL of specific groups
      of responders, comparing these groups respectively. However, if HRQoL assessment
      aims to contribute on deciding upon a suitable individual treatment and the
      evaluation thereof, as well as to identify hidden morbidities, an individual
      diagnostic perspective is required.To date, the majority of HRQoL questionnaires
      for children and adolescents are not designed for individual diagnostic
      assessment and comparison. This paper aims to demonstrate that should a
      particular measurement tool meet specific psychometric requirements - an
      individual diagnostic assessment on mental health related problems is possible.
      We investigated whether or not the KIDSCREEN-27 HRQoL instrument for children and
      adolescents is able to detect mental health problems in general, provided we
      apply a principal component analysis (PCA) for summative scaling. METHODS: The
      cross-sectional survey of the KIDSCREEN project was carried out in 13 European
      countries (AT, CH, CZ, DE, EL, ES, FR, HU, IE, NL, PL, SE, UK). The Rasch-scaled
      KIDSCREEN-27 test-data of 22,830 children and adolescents were analysed. To
      achieve a summative scaling PCA was performed on the correlation between the
      KIDSCREEN-27 scores. The principal component (PC) values were estimated and used
      to score the respondents. The reliability and diagnostic quality of this scoring
      was examined. RESULTS: The first PC accounted for 58.28% of the entire variance
      within the KIDSCREEN-27 scores. All KIDSCREEN scales loaded high on the first PC.
      The reliability of the linear combination of KIDSCREEN-27 scores with the PC
      values was rr=.94 and thus above the threshold for individual comparison. This
      value was higher than the values for the original single KIDSCREEN-27 scores
      (rr=.78-.84). The receiver operating characteristic curve (ROC) was calculated
      whilst screening for respondents with a mental health problem in general
      (Strengths and Difficulties Questionnaire). The area under the ROC (AuC) was .80
      and statistically significant lower than the AuC issued after a logistic
      regression analysis employing the 5 original KIDSCREEN-27 scores (AuC=.83).
      However, according to international conventions, both AuCs denote a "good"
      discrimination. CONCLUSION: Specifically for the KIDSCREEN-27 the results show
      that the application of a specific scoring algorithm leads to fulfil pre
      specified demands of high reliability. The applied scoring approach leads to a
      good discrimination of the measurement, thus enabling to detect a mental health
      problem in general using the HRQoL test-data. The presented approach can enhance
      the usability and range of application of HRQoL measurement.

PMID- 19742075
TI  - Do patient characteristics predict outcome in the outpatient treatment of chronic
      tinnitus?
AB  - Various patient characteristics were assessed before offering a treatment to
      reduce tinnitus related distress to 57 individuals suffering from chronic
      idiopathic tinnitus. Patients were randomly assigned to a cognitive-behavioral
      tinnitus coping training (TCT) and a habituation-based training (HT) modelled
      after Tinnitus Retraining Therapy (TRT) as conceived by Jastreboff. Both
      trainings were conducted in groups. It was hypothesized that comorbidity
      regarding mental disorders or psychopathological symptoms (DSM-IV diagnoses, SCL
      90R score) and a high level of dysfunctional cognitions relating to tinnitus
      would have a negative effect on therapy outcome while both trainings proved to be
      highly efficacious for the average patient. Also further patient features
      (assessed at baseline) were explored as potential predictors of outcome. None of
      the hypotheses was corroborated by the data. On the contrary, a higher number of
      diagnoses was associated with better outcome (statistical trend) and a higher
      extent of annoyance and interference led to a larger positive change in patients
      if treated by TCT. No predictor could be identified for long-term success (follow
      up >=18 months) except regarding education. The higher the educational level, the
      larger was the improvement in HT patients. It is concluded that therapy outcome
      of TCT and HT can not reliably be predicted by patient characteristics and that
      early variables of the therapeutic process should be analysed as potentially
      predicting subsequent therapeutic outcome.

PMID- 19742076
TI  - Ceramic on crosslinked polyethylene in total hip replacement: any better than
      metal on crosslinked polyethylene?
AB  - The authors evaluated the use of ceramic femoral heads on crosslinked
      polyethylene bearing couples versus metal on crosslinked polyethylene couples in
      a consecutive series of hips performed by a single surgeon over a one year
      interval. Ceramic femoral heads and more extensively crosslinked polyethylene
      were used more commonly in the younger aged patients with utilization of ceramic
      heads in patients average age 50.2 versus 63.9 for metal heads, and utilization
      of more extensively crosslinked polyethylene in patients average age 54.1 versus
      77.2 years for patients receiving less extensive crosslinked polyethylene. The
      authors explain the cost effectiveness of this approach where the difference in
      cost is approximately 36%.

PMID- 19742077
TI  - Component version in modular total hip revision.
AB  - Morphologic changes of the proximal femur make revision total hip arthroplasty
      challenging. Metaphyseal retroversion and diaphyseal varus are common in this
      scenario. Twenty-one total hip revisions using a modular femoral prosthesis were
      examined by obtaining three radiographs (A/P, surgical lateral, and true lateral
      of the femur) to assemble CAD models for determining the range of modular
      component positioning. An average of femoral neck anteversion was observed.
      Seventeen of 21 cases (81%) had retroverted metaphyseal segments (-23.2 degrees
      +/-17.4 degrees ) and/or varus stems (-32.1 degrees +/-13.0 degrees ). Neck
      anteversion averaged 21.4 degrees (+/-10.0 degrees ). One of 21 cases (5%)
      resulted in component orientation similar to a non-modular prosthesis. Modular
      components provide options to accommodate proximal femoral remodeling not
      afforded by monobloc stems in total hip revision surgery.

PMID- 19742078
TI  - Does functional improvement following TKA correlate to increased sports activity?
AB  - Improved TKA designs and surgical techniques have allowed surgeons to not only
      treat the pain associated with osteoarthritis but also to restore function. The
      present study analyzed whether the increase in physical activity of patients
      following surgery is associated with their level of functional and objective
      improvement. An activity questionnaire was utilized to collect pre- and post
      operative information from 355 patients (417 knees). Corresponding functional and
      objective assessments were collected using the Knee Society rating system.
      Overall, a mean 48 point (range, -44 to 97 points) improvement in Knee Society
      function score showed moderate correlation to a 2.5 point (range, -40 to 57
      points) increase in weighted activity score (R = 0.362). There was less of a
      correlation between the mean objective score increase of 49 points (-32 to 84
      points) and change in activity level (R = 0.194). There were 29% of the patients
      who showed no change in activity level. These results suggest that change in
      activity level is more closely associated with improved function than changes in
      objective measures. With more than 52% of TKA patients reporting increased
      activity scores, further studies are needed to assess longer-term effects of
      activity levels on the durability of these prostheses.

PMID- 19742079
TI  - Fractured cement spacers--a report of two cases.

PMID- 19742080
TI  - Mid-vastus vs medial para-patellar approach in total knee replacement--time to
      discharge.
AB  - BACKGROUND: It has been shown before that when compared with the medial para
      patellar approach, the mid-vastus approach for TKR results in less post-operative
      pain for patients and more rapid recovery of straight leg raise. As far as we are
      aware the post-operative length of stay of the two groups of patients has not
      been compared. We postulated that the reduced pain and more rapid recovery of
      straight leg raise would translate into an earlier, safe, discharge home for the
      mid-vastus patients compared with those who underwent a traditional medial para
      patellar approach. METHODS: Twenty patients operated on by each of five
      established knee arthroplasty surgeons were evaluated prospectively with regard
      to their pre and post-operative range of movement, time to achieve straight leg
      raise post-operatively and length of post-operative hospital stay. Only one of
      the surgeons performed the mid-vastus approach, and the measurements were
      recorded by physiotherapists who were blinded as to the approach used on each
      patient. RESULTS: The results were analysed using a standard statistical software
      package, and although the mean length of stay was lower for the mid-vastus
      patients, the difference did not reach a level of significance (p = 0.13). The
      time taken to achieve straight leg raise post-operatively was significantly less
      in the mid-vastus group (p<0.001). CONCLUSION: Although this study confirms
      previous findings that the mid-vastus approach reduces the time taken for
      patients to achieve straight leg raise, when compared with the medial para
      patellar approach, on its own it does not translate into a significantly shorter
      length of hospital stay. In order to reduce the length of post-operative hospital
      stay with an accelerated rehabilitation program for TKR, a multi-disciplinary
      approach is required. Patient expectations, GP support, physiotherapists and
      nursing staff all have a role to play and the mid-vastus approach, in permitting
      earlier straight leg raising, significantly contributes to this.

PMID- 19742081
TI  - Posterior-stabilized versus posterior cruciate ligament-retaining total knee
      arthroplasty.
AB  - Posterior-stabilized and posterior cruciate retaining total knee arthroplasty
      prostheses have had high success rates, but it is unclear whether one design has
      superior outcomes. The purpose of the present study was to directly compare the
      outcomes of these two designs. Forty-five patients who received a posterior
      stabilized prosthesis were compared to 46 consecutive patients who received a
      cruciate-retaining implant. At a mean follow-up time of 60 months (range, 49 to
      69 months), the mean Knee Society knee scores improved from 42 points (range, 20
      to 73 points) to 93 points (range, 39 to 100 points) for the cruciate-retaining
      group and from 38 points (range, 20 to 70 points) to 94 points (range, 60 to 100
      points) for the posterior-stabilized group. The mean Knee Society functional
      scores improved from 36 points (range, 10 to 60 points) to 71 points (range, 15
      to 100 points) for the cruciate-retaining group and from 32 points (range, 10 to
      70 points) to 73 points (range, 32 to 100 points) for the posterior-stabilized
      group. The ranges of motion were 125 degrees (range, 100 to 140 degrees ) and 118
      degrees (range, 87 to 135 degrees ) in the cruciate-retaining and posterior
      stabilized groups, respectively, at final follow-up. Radiographic analysis
      revealed no radiolucencies that were progressive or were greater than 1
      millimeter in length. There were no re-operations in either group. This study did
      not conclusively demonstrate the superiority of one knee design over the other,
      suggesting that the choice of implant should be based on surgeon preference and
      existing pathology of the posterior cruciate ligament.

PMID- 19742082
TI  - Revision total knee arthroplasty for major osteolysis.
AB  - Twenty-eight knees in 26 patients underwent revision TKA requiring surgical
      management of major osteolytic defects. Three groups of osteolytic defects were
      identified based upon the degree of implant stability and the magnitude of bone
      loss. Outcome measures included the Knee Society Clinical Rating Score (KSCRS),
      visual analog pain score, and radiographs. At a mean follow-up of 48 months, the
      average knee pain scores, range of motion, and KSCRS improved (p<.05). Ninety-six
      percent of the knees demonstrated clinical and functional improvement.
      Radiographs for 24 revision TKA's (86 percent) demonstrated component stability
      and incorporation of both cancellous and structural allografts. Revision TKA for
      major osteolytic defects may be effectively performed using a variety of bone
      grafting techniques. Both morselized and structural bone grafting, in combination
      with stemmed components was successful in managing revision TKA in the setting of
      major osteolysis. Significant improvement in clinical and radiographic outcomes
      may be anticipated using these surgical techniques.

PMID- 19742083
TI  - Characterization and pathological characteristics of spontaneous osteonecrosis of
      the knee.
AB  - OBJECTIVE: Spontaneous osteonecrosis of the knee affects patients typically over
      the age of fifty-five years. Evidence exists that this process may not be true
      necrosis. The purpose of this study was to characterize the demographic,
      radiographic, and pathologic features of this condition. MATERIALS AND METHODS:
      Twenty-one patients (twenty-two knees) consecutively treated for spontaneous
      osteonecrosis of the knee were studied. RESULTS: Only one of twenty-two specimens
      demonstrated evidence of bone necrosis. No specimens showed fat necrosis, marrow
      necrosis, fibrous change or appositional bone repair. Fourteen of twenty-two
      specimens (64%) showed significant osteopenia and fifteen of twenty-two specimens
      (68%) showed evidence of osteoarthritis. CONCLUSIONS: This study demonstrated
      that spontaneous osteonecrosis of the knee is not an osteonecrotic condition and
      has been misnamed. Osteopenia and osteoarthritis may play a role in the
      pathogenesis of this disease.

PMID- 19742084
TI  - Compliance-dependent load allocation between sensing versus non-sensing portions
      of a sheet-array contact stress sensor.
AB  - Piezoresistive array pressure sensors are widely used in orthopaedic research to
      determine contact stress distributions across articular joint surfaces.
      Experience with such sensors has shown there can be inaccuracies in how the
      sensor perceives applied load, depending on the material stiffnesses between
      which it is compressed experimentally, versus in calibration. A study was
      undertaken to quantify the relationship between load perception of one such
      sensor design (Tekscan) and the stiffness of the materials between which it is
      compressed. A three-dimensional finite element model of a 3x3 sensel portion of
      the sensing matrix was formulated, along with a layer of compression test
      material on each side of the sensor. The elastic modulus of the test material was
      varied across the range representative of cartilage (12 MPa) to hard plastic (10
      GPa). Using the computed contact pressure results between contacting surfaces of
      the sensor layers, the percentage of load passing through the active conductor
      intersections was determined. The results revealed that with increase of the
      elastic modulus of the material between which the sensor was compressed, the
      percentage of load on the active conductor intersections increased monotonically.
      The highest sensitivity of perceived loading to test material modulus (0.1%/MPa)
      was seen at the low end of the modulus range. The more compliant the test
      material, the more the sensor layers conformed around each other's geometric
      incongruities, the larger the true contact areas, and the higher the fraction of
      the total load that passed through the intermediate (non-sensing) regions between
      the conductors.

PMID- 19742085
TI  - Ia-FEMesh: anatomic FE models--a check of mesh accuracy and validity.
AB  - Musculoskeletal finite element (FE) analysis is an invaluable tool in orthopaedic
      research. Unfortunately, the demands that accompany anatomic mesh development
      often limit its utility. To ease the burden of mesh development and to address
      the need for subject-specific analysis, we developed IA-FEMesh, a user-friendly
      toolkit for generating hexahedral FE models. This study compared our multiblock
      meshing technique to widely accepted meshing methods. Herein, the meshes under
      consideration consisted of the phalanx bones of the index finger. Both accuracy
      and validity of the models were addressed. Generating a hexahedral mesh using IA
      FEMesh was found to be comparable to automated tetrahedral mesh generation in
      terms of preprocessing time. A convergence study suggested that the optimal
      number of hexahedral elements needed to mesh the distal, middle, and proximal
      phalanx bones were 3402, 4950, and 4550 respectively. Moreover, experimental
      studies were used to validate the mesh definitions. The contact areas predicted
      by the models compared favorably with the experimental findings (percent error <
      13.2%). With the accuracy and validity of the models confirmed, accompanied by
      the relative ease with which the models can be generated, we believe IA-FEMesh
      holds the potential to contribute to multi-subject analyses, which are pertinent
      for clinical studies.

PMID- 19742086
TI  - Comparison of two different anesthesia techniques for tourniquet pain with the
      use of forearm tourniquet.
AB  - PURPOSE: The purpose of this prospective, randomized study was to compare the
      effectiveness of two different anesthesia techniques for tourniquet pain in minor
      surgeries of the hand with the use of the forearm tourniquet. METHODS: In group
      1, the area under the tourniquet was anesthetized circumferentially using a cream
      composed of 5% lidocaine and 5% prilocaine (Emla Astra). In group 2, the area
      under the tourniquet was anesthetized with a ring-type infiltration of the skin
      and subcutaneus tissues using 50% diluted Citanest solution using 22 G x 3 1/2''
      size spinal needle (Sujia) with three injections. RESULTS: There were no
      statistically significant differences between the means of the two groups with
      respect to both tests (p value = 0.18 [t-test], p = 0.951 [Mann-Whitney test]).
      Tourniquet related anesthesia technique discomfort was higher in group 2 (p =
      0.001). CONCLUSIONS: The tourniquet placed at the distal forearm is an effective,
      safe, and useful technique for hand surgery. Anesthesia using Emla cream is
      equally effective and less disturbing than using the injection technique
      (subcutaneus ring anesthesia).

PMID- 19742087
TI  - Pre-operative and intra-operative factors related to shoulder arthroplasty
      outcomes.
AB  - The purpose of this study was to analyze pre-operative and intra-operative
      factors that affect the outcome of shoulder arthroplasty. We undertook a
      retrospective review of all shoulder arthroplasties performed at our institution
      between 1986 and 2003. Patients were contacted and outcomes were assessed using
      the Simple Shoulder Test and the Western Ontario Osteoarthritis of the Shoulder
      Index questionnaires. One hundred six patients (126 shoulders) participated in
      the study. The average length of follow-up was 6 years 9 months (range 2 to 20
      years). Revision arthroplasty surgery and female gender were associated with
      worse outcomes. Age, the number of medical comorbidities, obesity, pre-operative
      range of motion, prior non-arthroplasty surgery, smoking, and alcohol abuse did
      not correlate with outcome. Patients who had shoulder arthroplasty for
      osteoarthritis had better outcome scores than those with rheumatoid arthritis.
      For intra-operative variables, significantly worse outcomes were found both with
      the use of hemiarthroplasty and in patients with a rotator cuff tear identified
      at the time of surgery. These findings may help to optimize patient and surgery
      selection in shoulder arthroplasty and assist in preoperative patient counseling.

PMID- 19742088
TI  - Prevalence of methicillin resistant Staphylococcus aureus in upper extremity soft
      tissue infections at Jackson Memorial Hospital, Miami-Dade County, Florida.
AB  - PURPOSE: Methicillin resistant Staphylococcus aureus (MRSA) has been a hospital
      based problem since first being reported in the 1960s. Recent increases in
      outpatient MRSA infections suggest that there may be increased incidence of MRSA
      in upper extremity soft tissue infections (UESTIs). The aim of this study is to
      describe the current microbial flora responsible for UESTIs at an urban, tertiary
      care, teaching hospital. METHODS: A retrospective chart review was performed of
      all orthopaedic consultations for UESTIs from June 2006 to December 2007. The
      only exclusion criterion was a diagnosis of osteomyelitis. Logistic regression
      was used to describe the association between demographic and clinical
      characteristics identified on univariate analysis, and a MRSA positive culture.
      Odds ratios and confidence intervals are reported. RESULTS: There were 432
      orthopaedic consultations for UESTIs. Twelve cases of osteomyelitis were excluded
      per protocol. Therefore, 420 patients comprised our study population, ranging in
      age from 4 months to 95 years, (mean: 40 years), with 327 (77.9%) men and 93
      (22.1%) women. Wound cultures were available in 335 of 420 patients (79.8%).
      Positive cultures were found in 292 patients with a 53.4% MRSA rate (156 of 292).
      Methicillin sensitive Staphylococcus aureus was the second most prevalent
      microbe, found in 73 of 292 patients (25.0%). All MRSA isolates were susceptible
      to gentamicin and linezolid, and 98% or more were sensitive to vancomycin,
      rifampin, and trimethoprim-sulfamethoxazole combination. Univariate analyses and
      logistic regression identified infection location proximal to the wrist (Odds
      Ratio = 1.81, 95% Confidence Interval = 1.06-3.09, p<0.03) and diagnosis of
      abscess or felon (Odds Ratio = 3.22, 95% Confidence Interval = 1.84-5.63,
      p<0.001) as significantly associated with a MRSA positive culture. CONCLUSIONS:
      This is the largest study examining the prevalence of microbial flora in UESTIs.
      We found that MRSA has become the most common microbe in UESTIs comprising 53.4%,
      consistent with current trends at other urban medical centers.

PMID- 19742089
TI  - Aneurysmal bone cysts of the sacrum: a report of ten cases and review of the
      literature.
AB  - Ten cases of aneurysmal bone cysts are presented. Patients ranged in age from
      five years to 64 years. Treatment was resection or curettage; four patients had
      preoperative embolization. Treatment results were excellent. Six patients had no
      recurrence while recurrences in the other four patients were successfully treated
      by recurretage, two with adjunctive CyberKnife therapy. All ten patients are
      currently disease free for at least two years. Only two patients have residual
      neurologic deficit in the form of bowel or bladder dysfunction.

PMID- 19742090
TI  - Giant cell tumor of bone in elderly patients: a study of ten patients.

PMID- 19742091
TI  - Health promotion program: a resident well-being study.
AB  - BACKGROUND: Surgical training places unique stresses on residents that can lead
      to decreased levels of presenteeism. We hypothesized that presenteeism levels
      could be positively influenced by improving workplace hygiene. METHODS: a cohort
      of surgical residents was asked to complete the Stanford Presenteeism Scale:
      Health Status and Employee Productivity (SPS-6) questionnaire before, and one
      year after the implementation of a workplace health promotion program. RESULTS:
      Twenty-six of thirty-three residents responded to the initial survey and reported
      a mean SPS-6 score of 17.3 +/- 4.5, well below population normative value of 24
      +/- 3 (p < 0.0001). At one-year post intervention 25 of 32 residents responded,
      reporting a mean SPS-6 score of 18.3+/- 4.6. The mean SPS-6 score improved by
      1.2+/- 3.8 (p = 0.35). Subgroup analysis showed a trend toward improved SPS-6 in
      those who participated in the health promotion program (p = 0.15) and a
      significant difference when junior residents were compared to seniors (p =
      0.034). Overall, results were limited by our small sample size. CONCLUSIONS:
      Presenteeism scores for surgical residents at our institution are well below
      population values. Use of validated tools such as the SPS-6 may allow for more
      objective analysis and decision making when planning for resident education and
      workload. PRESENTEEISM: the ability while on the job to produce quality work at
      maximum productivity. DECREASED PRESENTEEISM: a state of decreased productivity
      and below-normal work quality related to health/workplace distracters.

PMID- 19742092
TI  - Are honors received during surgery clerkships useful in the selection of incoming
      orthopaedic residents?
AB  - The purpose of this study was to review institutional statistics provided in
      dean's letters and determine the percentage of honors awarded by institution and
      clerkship specialty.Institutional and clerkship aggregate data were compiled from
      a review of dean's letters from 80 United States medical schools. The percentage
      of honors awarded during 3rd year clerkships during 2005 were collected for
      analysis. Across clerkship specialties, there were no statistically significant
      differences between the mean percentage of honors given by the medical schools
      examined with Internal Medicine (27.6%) the low and Psychiatry (33.5%) the high.
      However, inter-institutional variability observed within each clerkship was high,
      with surgery clerkship percentage of honors ranging from 2% to 75% of the
      students. This suggests some schools may be more lenient and other more stringent
      in awarding honors to their students. This inter-institutional variability makes
      it difficult to compare honors received by students from different medical
      schools and weakens the receipt of honors as a primary tool for evaluating
      potential incoming residents.

PMID- 19742093
TI  - Comparable effectiveness of caudal vs. trans-foraminal epidural steroid
      injections.
AB  - STUDY DESIGN: Retrospective case-control study. OBJECTIVE: To compare the
      effectiveness between caudal and trans-foraminal epidural steroid injections for
      the treatment of primary lumbar radiculopathy. SUMMARY OF BACKGROUND DATA: Spinal
      injections with steroids play an important role in non-operative care of lumbar
      radiculopathy. The trans-foraminal epidural steroid injection (TESI)
      theoretically has a higher success rate based on targeted delivery to the
      symptomatic nerve root. To our knowledge, these results have not been compared
      with other techniques of epidural steroid injection. METHODS: 93 patients
      diagnosed with primary lumbar radiculopathy of L4, L5, or SI were recruited for
      this study: 39 received caudal epidural steroid injections (ESI) and 54 received
      trans-foraminal epidural steroid injections (TESI). Outcomes scores included the
      SF-36, Oswestry disability index (ODI) and pain visual analogue scale (VAS), and
      were recorded at baseline, post-treatment (<6 months), long-term (>1 year). The
      average follow-up was 2 years, and 16 patients were lost to follow-up. The
      endpoint "surgical intervention" was a patient-driven decision, and considered
      failure of treatment. Intent-to-treat analysis, and comparisons included t-test,
      Chi-square, and Wilcoxon rank-sum test. RESULTS: Baseline demographics and
      outcomes scores were comparable for both treatment groups (ESI vs. TESI): (SF-36
      PCS (32.3 +/- 7.5 vs. 29.5 +/- 8.9 respectively; p = 0.173), MCS (41.2 +/- 12.7
      vs. 41.1 +/- 10.9, respectively; p = 0.971), and VAS (7.4 +/-2.1 vs. 7.9 +/- 1.2,
      respectively; p = 0.228)). Surgery was indicated for failure of treatment at a
      similar rate for both groups (41.0% vs. 44.4%, p=0.743). Symptom improvement was
      comparable between both treatment groups (ESI vs. TESI): SF-36 PCS improved to
      42.0+/-11.8 and 37.7+/-12.3, respectively; p=0.49; ODI improved from 50.0+/-21.2
      to 15.6+/-17.9and from 62.1+/-17.9 to 26.1+/-20.3, respectively (p=0.407).
      CONCLUSIONS: The effectiveness of TESI is comparable to that of ESI
      (approximately 60%) for the treatment of primary lumbar radiculopathy. The
      increased complexity of TESI is not justified for primary cases, and may have a
      more specific role in recurrent disease or for diagnostic purposes.

PMID- 19742094
TI  - Pilot data: association between gluteus medius weakness and low back pain during
      pregnancy.
AB  - This cross-sectional study examines whether there is an association between
      gluteus medius weakness in the presence of low back pain in pregnant women at any
      stage of gestation. Prevalence of low back pain during pregnancy is high, and
      identifying potential etiologies and targeted interventions is lacking. Thus,
      identification of an association between specific muscle weakness and pain would
      have clinical relevance. Initial pilot data suggests that weakness of the gluteus
      medius is strongly associated with the presence of low back pain during
      pregnancy.

PMID- 19742095
TI  - Bilateral patellar tendon rupture at different sites without predisposing
      systemic disease or steroid use.
AB  - Simultaneous bilateral patellar tendon ruptures are extremely rare, and even more
      rare in patients without systemic disease. We describe bilateral simultaneous
      patellar tendon disruptions in the absence of systemic disease or steroid usage,
      with one tendon disruption at the inferior pole and the other an intrasubstance
      tear. The different locations of the ruptures are also exceedingly rare, as only
      two cases of non-identical ruptures have ever been reported. We also review all
      bilateral patellar tendon rupture case reports from English and German
      literature.

PMID- 19742097
TI  - Chloroma of the forearm: a case report of leukemia recurrence presenting with
      compression neuropathy and tenosynovitis.
AB  - Acute Myelogenous Leukemia (AML) typically involves intramedullary proliferation
      of myeloid precursor cells. Extramedullary manifestations of AML are exceedingly
      rare, but do occur. Granu-locytic sarcoma, or chloroma, is one example of
      extramedullary leukemia cells forming a tumorous mass. We report a case of
      Chloroma in the volar forearm compartment presenting with both median nerve
      compressive neuropathy and apparent tenosynovitis. Abscess was at the top of the
      early differential, and the patient was scheduled for operative debridement.
      However, further evaluation indicated that chloroma was present, thus obviating
      the need for emergent surgical intervention and necessitating the induction of
      chemotherapy. To our knowledge this is the first report of chloroma in this
      location and with these presenting symptoms.

PMID- 19742096
TI  - Case report and literature review anterior shoulder dislocation with three-part
      proximal humerus fracture and humeral shaft fracture.
AB  - Dislocation of the shoulder and proximal humerus fracture with coexistent humeral
      shaft fracture is a rare injury reported in literature. There have been a total
      of 20 cases reported in the literature since 19401-13 (see Table 1). These
      injuries often occur as a result of high velocity trauma and most have been
      treated, at least partially, with invasive or operative management. We present
      the case of a woman with an anterior dislocation, three-part proximal humerus
      fracture and concomitant humerus shaft fracture and discuss her non-invasive
      treatment.

PMID- 19742098
TI  - Distal tibia/fibula fractures following clubfoot casting---report of four cases.

PMID- 19742099
TI  - Pilomatrixoma of the forearm: a case report.
AB  - Pilomatrixoma is a benign neoplasm derived from hair follicle matrix cells.
      Involvement of the upper extremities is relatively uncommon and can be mistaken
      for malignancy. We present the case of a 52-year-old woman with a pilomatrixoma
      of the forearm, and we review the literature regarding pilomatrixomas in the
      upper extremity.

PMID- 19742100
TI  - Septic arthritis of the hip associated with supra-acetabular external fixation of
      unstable pelvic ring: a case report.

PMID- 19742101
TI  - History of self-experimentation in orthopaedics.

PMID- 19742102
TI  - High ankle sprains (syndesmotic) in athletes: diagnostic challenges and review of
      the literature.

PMID- 19742103
TI  - The future of UIHC Rehabilitation Services: defining and measuring quality
      rehabilitation services.

PMID- 19742104
TI  - The direct lateral approach to the distal tibia and fibula: a single incision
      technique for distal tibial and pilon fractures.
AB  - Distal tibia fractures remain difficult injuries to treat when fracture
      displacement precludes non-operative treatment. Different methods of treatment
      including limited internal fixation with external fixation, as well as open
      reduction and internal fixation have been recommended. Open reduction and
      internal fixation is often favored for the improved ability to anatomically
      reduce displaced fractures, particularly articular fractures. However, wound
      complications due to the associated trauma to the fragile soft tissue envelope in
      this region continue to be a significant concern.The authors present a surgical
      approach for open reduction and fixation of distal tibia and fibula fractures
      through a single lateral incision, which respects the angiosomes of the distal
      leg and ankle. This can, in some cases, resolve the need to delay ORIF of the
      tibia since the incision is essentially the same as that used for the immediate
      ORIF of fibula fractures, which is commonly used in the staged treatment of
      distal tibial and plafond fractures. This approach can be extended proximally and
      distally to allow treatment of other injuries about the ankle and hindfoot.
      Illustrative cases are provided.

PMID- 19742105
TI  - Variability in antagonist muscle activity and peak torque during isometric knee
      strength testing.
AB  - BACKGROUND & OBJECTIVE: Strength testing is common in the treatment of people
      with knee pathology and in research related to knee health. Variability in the
      magnitude of antagonist muscle activity and peak torque measurements during
      isometric knee strength testing is not well defined and has potential
      implications of strength test validity and reliability. The aim of this study was
      to determine the magnitude and variability (side-to-side, session-to-session) of
      antagonist muscle activity and peak torque during isometric knee strength testing
      and to compare and contrast the results of males and females. METHODS:
      Electromyograms and torque data were collected from 30 active young people (15
      males, 15 females) during isometric strength testing of the knee extensors and
      flexors at two sessions that took place approximately one week apart. The
      magnitude of antagonist muscle activity and peak torque during isometric knee
      strength testing was calculated and the variability in these parameters assessed.
      RESULTS: Significant side-to-side differences were observed in the magnitude of
      antagonist muscle activity when the leg with higher antagonist activity was
      contrasted with the leg with lower antagonist activity (P < 0.001). Significant
      side-to-side differences were also observed when peak torque measurements were
      contrasted in a similar manner (P < 0.001). No significant differences were
      observed in peak torque and antagonist activity measurements between sessions.
      Significantly higher vastus medialis antagonist activity was observed in females
      (P < 0.001). CONCLUSIONS: Our findings suggest that significant variability in
      antagonist muscle activity and peak torque is present during maximal isometric
      knee strength testing. This variability may reduce the accuracy of knee strength
      tests, especially when side-to-side comparisons are made as is typical in
      clinical settings. The results of this study may be helpful when interpreting
      strength test results and setting criteria for patient progression.

PMID- 19742119
TI  - Michael Foster and Thomas Henry Huxley, Correspondence, 1865-1895. Introduction.

PMID- 19742120
TI  - Michael Foster and Thomas Henry Huxley, Correspondence, 1865-1895. Editors' note.

PMID- 19742121
TI  - Molecular characterization of Tb, a new approach for an ancient Brucellaphage.
AB  - Tb (Tbilisi), the reference Brucellaphage strain, was classified as a member of
      the Podoviridae family with icosahedral capsids (57 +/- 2 nm diameter) and short
      tails (32 +/- 3 nm long). Brucellaphage DNA was double stranded and unmethylated;
      its molecular size was 34.5 kilobase pairs. Some sequences were found through
      RAPD analysis, TA cloning technology, and structural proteins were observed by
      using SDS-PAGE. Thus, the results have laid the foundation for the wider use of
      Brucellaphage's basic mechanisms and practical applications.

PMID- 19742122
TI  - Protein and metabolite analysis reveals permanent induction of stress defense and
      cell regeneration processes in a tobacco cell suspension culture.
AB  - The secretome of a tobacco cell suspension culture was investigated by a combined
      proteomic and metabolomic approach. Protein analysis from 2-DE gels led to
      identification of 32 out of 60 spots from culture medium. Identified proteins
      were mainly involved in stress defence and cell regeneration processes. Among
      them three putative new isoforms, e.g. for chitinase, peroxidase and beta-1,4
      xylosidase were identified, not yet present in available protein databases for
      the genus Nicotiana. GC-MS analysis of time course experiments revealed
      significant changes for metabolites involved in energy transport, signalling and
      cell development. Among them, the most significant increase was found for
      putrescine in the medium of cultures entering the exponential phase. Results
      showed strong abundance of stress associated proteins and metabolites in the
      absence of elicitors or additional stress treatments.

PMID- 19742123
TI  - Hedgehog signaling regulates the survival of gastric cancer cells by regulating
      the expression of Bcl-2.
AB  - Gastric cancer is the second most common cause of cancer deaths worldwide. The
      underlying molecular mechanisms of its carcinogenesis are relatively poorly
      characterized. Hedgehog (Hh) signaling, which is critical for development of
      various organs including the gastrointestinal tract, has been associated with
      gastric cancer. The present study was undertaken to reveal the underlying
      mechanism by which Hh signaling controls gastric cancer cell proliferation.
      Treatment of gastric cancer cells with cyclopamine, a specific inhibitor of Hh
      signaling pathway, reduced proliferation and induced apoptosis of gastric cancer
      cells. Cyclopamine treatment induced cytochrome c release from mitochondria and
      cleavage of caspase 9. Moreover, Bcl-2 expression was significantly reduced by
      cyclopamine treatment. These results suggest that Hh signaling regulates the
      survival of gastric cancer cells by regulating the expression of Bcl-2.

PMID- 19742124
TI  - Chirality emergence in thin solid films of amino acids by polarized light from
      synchrotron radiation and free electron laser.
AB  - One of the most attractive hypothesis for the origin of homochirality in
      terrestrial bioorganic compounds is that a kind of "chiral impulse" as an
      asymmetric excitation source induced asymmetric reactions on the surfaces of such
      materials such as meteorites or interstellar dusts prior to the existence of
      terrestrial life (Cosmic Scenario). To experimentally introduce chiral structure
      into racemic films of amino acids (alanine, phenylalanine, isovaline, etc.), we
      irradiated them with linearly polarized light (LPL) from synchrotron radiation
      and circularly polarized light (CPL) from a free electron laser. After the
      irradiation, we evaluated optical anisotropy by measuring the circular dichroism
      (CD) spectra and verified that new Cotton peaks appeared at almost the same peak
      position as those of the corresponding non-racemic amino acid films. With LPL
      irradiation, two-dimensional anisotropic structure expressed as linear dichroism
      and/or linear birefringence was introduced into the racemic films. With CPL
      irradiation, the signs of the Cotton peaks exhibit symmetrical structure
      corresponding to the direction of CPL rotation. This indicates that some kinds of
      chiral structure were introduced into the racemic film. The CD spectra after CPL
      irradiation suggest the chiral structure should be derived from not only
      preferential photolysis but also from photolysis-induced molecular structural
      change. These results suggest that circularly polarized light sources in space
      could be associated with the origin of terrestrial homochirality; that is, they
      would be effective asymmetric exciting sources introducing chiral structures into
      bio-organic molecules or complex organic compounds.

PMID- 19742125
TI  - Effect of seven newly synthesized and currently available oxime cholinesterase
      reactivators on cyclosarin-intoxicated rats.
AB  - Seven new oxime-based acetylcholinesterase reactivators were compared with three
      currently available ones (obidoxime, trimedoxime, HI-6) for their ability to
      lessen cholinesterase inhibition in blood and brain of cyclosarin-treated rats.
      Oximes were given at doses of 5% their LD(50) along with 21 mg/kg atropine five
      min before the LD(50) of cyclosarin (120 ug/kg) was administered. Blood and brain
      samples were collected 30 minutes later. The greatest difference between
      acetylcholinesterase inhibition in blood of cyclosarin-treated rats was found
      after administration of HI-6 (40%), compared to 22% for trimedoxime and 6% for
      obidoxime. Only two of the seven newly synthesized oximes had any effect (K203 at
      7%, K156 at 5%). Effective oximes against cyclosarin-inhibited plasma
      butyrylcholinesterase were HI-6 (42%), trimedoxime (11%), and K156 (4%). The
      oximes were less effective in brain than in blood, with reactivation values for
      HI-6 30% against acetylcholinesterase and 10% against butyrylcholinesterase.
      Values for newly synthesized oximes were less than 10% for K206, K269 and K203.

PMID- 19742127
TI  - Additive SMILES-based carcinogenicity models: Probabilistic principles in the
      search for robust predictions.
AB  - Optimal descriptors calculated with the simplified molecular input line entry
      system (SMILES) have been utilized in modeling of carcinogenicity as continuous
      values (logTD(50)). These descriptors can be calculated using correlation weights
      of SMILES attributes calculated by the Monte Carlo method. A considerable subset
      of these attributes includes rare attributes. The use of these rare attributes
      can lead to overtraining. One can avoid the influence of the rare attributes if
      their correlation weights are fixed to zero. A function, limS, has been defined
      to identify rare attributes. The limS defines the minimum number of occurrences
      in the set of structures of the training (subtraining) set, to accept attributes
      as usable. If an attribute is present less than limS, it is considered "rare",
      and thus not used. Two systems of building up models were examined: 1. classic
      training-test system; 2. balance of correlations for the subtraining and
      calibration sets (together, they are the original training set: the function of
      the calibration set is imitation of a preliminary test set). Three random splits
      into subtraining, calibration, and test sets were analysed. Comparison of above
      mentioned systems has shown that balance of correlations gives more robust
      prediction of the carcinogenicity for all three splits (split 1: r(test)
      (2)=0.7514, s(test)=0.684; split 2: r(test) (2)=0.7998, s(test)=0.600; split 3:
      r(test) (2)=0.7192, s(test)=0.728).

PMID- 19742126
TI  - Bacterial stressors in minimally processed food.
AB  - Stress responses are of particular importance to microorganisms, because their
      habitats are subjected to continual changes in temperature, osmotic pressure, and
      nutrients availability. Stressors (and stress factors), may be of chemical,
      physical, or biological nature. While stress to microorganisms is frequently
      caused by the surrounding environment, the growth of microbial cells on its own
      may also result in induction of some kinds of stress such as starvation and
      acidity. During production of fresh-cut produce, cumulative mild processing steps
      are employed, to control the growth of microorganisms. Pathogens on plant
      surfaces are already stressed and stress may be increased during the multiple
      mild processing steps, potentially leading to very hardy bacteria geared towards
      enhanced survival. Cross-protection can occur because the overlapping stress
      responses enable bacteria exposed to one stress to become resistant to another
      stress. A number of stresses have been shown to induce cross protection,
      including heat, cold, acid and osmotic stress. Among other factors, adaptation to
      heat stress appears to provide bacterial cells with more pronounced cross
      protection against several other stresses. Understanding how pathogens sense and
      respond to mild stresses is essential in order to design safe and effective
      minimal processing regimes.

PMID- 19742128
TI  - Density functional study of structures and electron affinities of BrO4F/BrO4F-.
AB  - The structures, electron affinities and bond dissociation energies of
      BrO(4)F/BrO(4)F(-) species have been investigated with five density functional
      theory (DFT) methods with DZP++ basis sets. The planar F-Br...O(2)...O(2)
      complexes possess (3)A' electronic state for neutral molecule and (4)A' state for
      the corresponding anion. Three types of the neutral-anion energy separations are
      the adiabatic electron affinity (EA(ad)), the vertical electron affinity
      (EA(vert)), and the vertical detachment energy (VDE). The EA(ad) value predicted
      by B3LYP method is 4.52 eV. The bond dissociation energies D(e) (BrO(4)F -->
      BrO(4-m)F + O(m)) (m = 1-4) and D(e) (-) (BrO(4)F(-) --> BrO(4-m)F(-) + O(m) and
      BrO(4)F(-) --> BrO(4-m)F + O(m) (-)) are predicted. The adiabatic electron
      affinities (EA(ad)) were predicted to be 4.52 eV for F-Br...O(2)...O(2) ((3)A'<-
      (4)A') (B3LYP method).

PMID- 19742130
TI  - Post-transcriptional regulation of gene expression in plants during abiotic
      stress.
AB  - Land plants are anchored in one place for most of their life cycle and therefore
      must constantly adapt their growth and metabolism to abiotic stresses such as
      light intensity, temperature and the availability of water and essential
      minerals. Thus, plants' subsistence depends on their ability to regulate rapidly
      gene expression in order to adapt their physiology to their environment. Recent
      studies indicate that post-transcriptional regulations of gene expression play an
      important role in how plants respond to abiotic stresses. We will review the
      different mechanisms of post-transcriptional regulation of nuclear genes
      expression including messenger RNA (mRNA) processing, stability, localization and
      protein translation, and discuss their relative importance for plant adaptation
      to abiotic stress.

PMID- 19742129
TI  - Bax Inhibitor-1, a conserved cell death suppressor, is a key molecular switch
      downstream from a variety of biotic and abiotic stress signals in plants.
AB  - In Nature plants are constantly challenged by a variety of environmental stresses
      that could lead to disruptions in cellular homeostasis. Programmed cell death
      (PCD) is a fundamental cellular process that is often associated with defense
      responses to pathogens, during development and in response to abiotic stresses in
      fungi, animals and plants. Although there are many characteristics shared between
      different types of PCD events, it remains unknown whether a common mechanism
      drives various types of PCD in eukaryotes. One candidate regulator for such a
      mechanism is Bax Inhibitor-1 (BI-1), an evolutionary conserved, endoplasmic
      reticulum (ER)-resident protein that represents an ancient cell death regulator
      that potentially regulates PCD in all eukaryotes. Recent findings strongly
      suggested that BI-1 plays an important role in the conserved ER stress response
      pathway to modulate cell death induction in response to multiple types of cell
      death signals. As ER stress signaling pathways has been suggested to play
      important roles not only in the control of ER homeostasis but also in other
      biological processes such as the response to pathogens and abiotic stress in
      plants, BI-1 might function to control the convergence point that modulates the
      level of the "pro-survival and pro-death" signals under multiple stress
      conditions.

PMID- 19742131
TI  - A TD-DFT study on the photo-physicochemical properties of chrysophanol from
      rheum.
AB  - As a naturally occurring anthraquinone pigment, chrysophanol (MHAQ) has attracted
      considerable attention in recent years owing to its efficient photosensitivity
      under the solar spectrum. Considering the successful use of time-dependent
      density functional theory (TD-DFT) in investigating the photo-physicochemical
      behaviors of dyes and pigments, we performed a study by means of TD-DFT
      calculations, which provided us with various excited state properties of
      chrysophanol, including absorption spectrum, lowest triplet excited-state energy,
      vertical electron affinity and vertical ionization potential. On the basis of the
      calculated results, the photosensitive mechanisms of chrysophanol were discussed
      and some deeper insights were gained. First, we indicated that the experimentally
      observed chrysophanol's photo-damage to DNA in oxygen-free media is more likely
      to arise from MHAQ(*+) rather than from T(1) state chrysophanol. Second, we
      revealed that it is the MHAQ(*-) that is responsible for the O(2) (*-) generation
      in solvents. Based on the photosensitive activities, chrysophanol may be
      potentially used as the photodynamic medicine for clinical therapy of the
      diseases occurring on the shallow surface and vascular capillary diseases.

PMID- 19742132
TI  - Receptor-mediated vascular smooth muscle migration induced by LPA involves p38
      mitogen-activated protein kinase pathway activation.
AB  - Lysophosphatidic acid (LPA), a naturally occurring glycerophospholipid, can evoke
      various biological responses, including cell migration, proliferation and
      survival, via activation of G protein-coupled receptors (GPCRs). However, the
      role of LPA receptors and details of LPA signaling in migration are largely
      unexplored. In this study we detect the expression of LPA1 and LPA3 receptors in
      rat aortic smooth muscle cells (RASMCs). LPA stimulated RASMCs migration in a
      dose-dependent manner and induced the phosphorylation of p38 mitogen-activated
      protein kinase (p38MAPK) and extracellular signal-regulated kinase (ERK). LPA
      induced cell migration was significantly inhibited by specific LPA1/LPA3-receptor
      antagonist Dioctylglycerol pyrophosphate (8:0) (DGPP8.0) at higher concentration.
      Migration of cells toward LPA was partially, but significantly, reduced in the
      presence of SB-203580, a p38 MAPK inhibitor, but not PD98059, an ERK inhibitor.
      In addition, pertussis toxin (PTX), a Gi protein inhibitor, induced an inhibitory
      effect on p38 MAPK, ERK phosphorylation and RASMCs migration. These data suggest
      that LPA-induced migration is mediated through the Gi-protein-coupled LPA1
      receptor involving activation of a PTX-sensitive Gi / p38MAPK pathway.

PMID- 19742133
TI  - Biofouling growth in cold estuarine waters and evaluation of some chitosan and
      copper anti-fouling paints.
AB  - Ecological concerns about antifouling paints containing non-green tin and copper
      compounds have highlighted the need for environmentally friendly alternatives. We
      report here a field test conducted in estuarine waters over two months designed
      to evaluate the efficiency of a number of active natural and man-made chemical
      ingredients added into a silicon-polyurethane marine paint. Early steps of
      biofouling in cold seawater of the St. Lawrence Estuary (Canada) were observed.
      Analyses, including dry biomass, flow cytometry and spectrofluorimetry,
      demonstrated a short-term antibacterial action of chitosan-based paints although
      no significant anti-algal action was observed. Cuprous oxide paints were
      efficient against bacteria and algae invasion in the first two weeks, especially
      those with added organic biocides such as isothiazolone and copper pyrithione.
      However, the overall dry biomass and chlorophyll a content were similar for all
      chitosan-and copper-based paints after 63 days. Microscopic observations revealed
      variation in the highly diverse benthic diatom population including species
      Navicula, Melosira, Cocconeis, Nitshzcia, Fragilaria and Amphora. Results suggest
      no real long-term efficiency for tested antifouling paints and highlight a
      particular need for green antifouling ingredients that are active under northern
      estuarine conditions.

PMID- 19742134
TI  - The evaluation of the possibilities of using PLGA co-polymer and its composites
      with carbon fibers or hydroxyapatite in the bone tissue regeneration process - in
      vitro and in vivo examinations.
AB  - Synthetic polymers belonging to the aliphatic polyester group have become highly
      promising biomaterials for reconstructive medicine. The purpose of the present
      work is a biological evaluation of lactide-glycolide co-polymer (PLGA) and its
      composites with carbon fibers (PLGA+CF) or hydroxyapatite (PLGA+HA). The
      cytotoxicity of the evaluated materials towards hFOB 1.19 human osteoblast-like
      cells was assessed. Moreover, during the one-year contact of the assessed
      materials with living osseous tissue, the progress of bone formation was analyzed
      and the accompanying process of the materials' degradation was evaluated. The
      materials under evaluation proved to be biocompatible.

PMID- 19742135
TI  - Fuels for thought!

PMID- 19742136
TI  - Prediction of skin sensitization with a particle swarm optimized support vector
      machine.
AB  - Skin sensitization is the most commonly reported occupational illness, causing
      much suffering to a wide range of people. Identification and labeling of
      environmental allergens is urgently required to protect people from skin
      sensitization. The guinea pig maximization test (GPMT) and murine local lymph
      node assay (LLNA) are the two most important in vivo models for identification of
      skin sensitizers. In order to reduce the number of animal tests, quantitative
      structure-activity relationships (QSARs) are strongly encouraged in the
      assessment of skin sensitization of chemicals. This paper has investigated the
      skin sensitization potential of 162 compounds with LLNA results and 92 compounds
      with GPMT results using a support vector machine. A particle swarm optimization
      algorithm was implemented for feature selection from a large number of molecular
      descriptors calculated by Dragon. For the LLNA data set, the classification
      accuracies are 95.37% and 88.89% for the training and the test sets,
      respectively. For the GPMT data set, the classification accuracies are 91.80% and
      90.32% for the training and the test sets, respectively. The classification
      performances were greatly improved compared to those reported in the literature,
      indicating that the support vector machine optimized by particle swarm in this
      paper is competent for the identification of skin sensitizers.

PMID- 19742138
TI  - ISGIO: Setting the Standard of Care for the Future.

PMID- 19742137
TI  - Genistein inhibition of topoisomerase IIalpha expression participated by Sp1 and
      Sp3 in HeLa cell.
AB  - Genistein (4', 5, 7-trihydroxyisoflavone) is an isoflavone compound obtained from
      plants that has potential applications in cancer therapy. However, the molecular
      mechanism of the action of genistein on cancer cell apoptosis is not well known.
      In this study, we investigated the effect of genistein on topoisomerase II-alpha
      (Topo IIalpha), an important protein involved in the processes of DNA replication
      and cell proliferation. The results revealed that inhibition of Topo IIalpha
      expression through the regulation of Specificity protein 1 and Specificity
      protein 3 may be one of the reasons for genistein's induction of HeLa cell
      apoptosis.

PMID- 19742139
TI  - Safety of chronic low-dose capecitabine as maintenance therapy in
      gastrointestinal cancers.
AB  - BACKGROUND: Maintenance chemotherapy is not routinely used in gastrointestinal
      (GI) cancers. Capecitabine is an oral formulation that is enzymatically converted
      to 5-fluorouracil preferentially in tumor tissue. We hypothesize that
      capecitabine could be used as a long-term maintenance therapy to improve outcomes
      in patients with high-risk GI cancers following standard chemotherapy regimens.
      METHODS: We conducted a retrospective study to assess the toxicity of maintenance
      capecitabine in 28 patients with a variety of advanced GI malignancies.
      Capecitabine 1,000 mg twice daily without interruption was used for the first 11
      patients. The dose was reduced to 1,000 mg twice daily 5 days per week in 8
      patients who developed hand-foot syndrome. The remaining patients began treatment
      on the same abbreviated schedule. All documented clinical adverse events were
      graded according to the National Cancer Institute Common Terminology Criteria for
      Adverse Events (v3.0, 2003). RESULTS: Main toxicities were grade 1/2 fatigue and
      hand-foot syndrome. Only one grade 3 toxicity was observed and no grade 4
      toxicities were seen. We also observed a significant increase in red blood cell
      mean corpuscular volume in participants, which may have potential use as a
      biomarker to monitor therapeutic response. CONCLUSIONS: Fixed therapeutic doses
      of oral capecitabine 1,000 mg twice daily, 5 days on, 2 days off, can be
      administered chronically with a high level of safety and should be explored in
      larger prospective studies to demonstrate efficacy in GI malignancies, especially
      pancreatic and metastatic colorectal cancers.

PMID- 19742140
TI  - Influence of Diabetes on the Interpretation of PET Scans in Patients With
      Esophageal Cancer.
AB  - PURPOSE: Patients with diabetes mellitus (DM) can have altered sugar transport
      into cells, potentially affecting the results of 18-FDG PET scans. The specific
      aim of this study was to determine the effect of DM on pre- and post-treatment
      standard uptake value (SUV) scores in patients undergoing chemoradiotherapy for
      esophageal cancer. METHODS: Patients with locally advanced esophageal carcinoma
      undergoing preoperative or definitive chemoradiotherapy underwent pre- and
      posttreatment 18-FDG PET scans. Maximum SUV score was measured from the tumor
      before chemoradiotherapy and 3 to 4 weeks after chemoradiotherapy
      (preoperatively). Patients were identified as having DM by medical record review.
      Random serum glucose measurements were obtained prior to 18-FDG PET scans. The
      Wilcoxon signed-rank test was used to test for differences in SUV scores between
      patients with and without DM, and a generalized linear model with backward
      selection was applied to search for significant predictors of initial and
      posttreatment SUV scores. RESULTS: Sixty-three patients underwent 18-FDG PET
      scans during the course of treatment for esophageal malignancies between 6/02 and
      8/05. Fifty-four patients received chemotherapy. The median radiation dose was
      46.8 Gy. Eighteen patients had DM, six were insulin-dependent DM (IDDM). There
      was no difference in initial SUV scores between DM and non-DM patients (P > .05).
      There was also no difference in initial SUV scores between IDDM and non-IDDM
      groups. Patients with tumors at the gastroesophageal junction had lower initial
      SUV scores compared to patients with tumors in the lower or mid-esophagus (P =
      .05). T stage was associated with initial SUV score (T2 lower than T3, P = .014).
      Older age (P = .03), diabetes (P = .007), higher T stage (P = .002), and presence
      of nodes (P = .05) were each positively associated with posttreatment SUV scores.
      Blood glucose levels prior to 18-FDG PET scan, endoscopic tumor length, and tumor
      location were not predictive of posttreatment SUV scores. Patients with DM had
      significantly lower posttreatment SUV scores compared to patients without DM (P =
      .04). Pathologic complete response or percent SUV decrease did not differ between
      patients with or without DM. CONCLUSION: Regardless of glucose levels, DM and
      IDDM do not influence pretreatment SUV scores in patients with localized
      esophageal cancer. However, DM may influence posttreatment SUV scores and thus
      complicate interpretation of treatment response. Further confirmatory study in a
      larger cohort of DM patients to evaluate the relationship of posttreatment SUV
      score to pathologic response is warranted.

PMID- 19742141
TI  - Current management of esophageal squamous-cell carcinoma in Japan and other
      countries.
AB  - The incidence of adenocarcinoma of the distal esophagus or esophagogastric
      junction has increased considerably in Western countries during the past 3
      decades, whereas the incidence of squamous-cell carcinoma has decreased slightly.
      In Japan, most esophageal cancers are squamous-cell carcinomas. Endoscopic
      examinations are more frequently performed in Japan for routine screening and
      diagnosis and treatment than in other countries, thereby increasing the detection
      rate of superficial esophageal carcinomas. In Europe and North America, many
      clinical trials have been conducted to assess the effectiveness of neoadjuvant
      chemoradiotherapy followed by surgery in patients with resectable, advanced
      esophageal cancer. In Japan, surgical resection had been the mainstay of
      treatment for esophageal cancer. Since the results of the Japan Clinical Oncology
      Group (JCOG) 9907 study were reported, neoadjuvant chemotherapy with cisplatin
      plus 5-fluorouracil followed by surgery has emerged as a new standard treatment.
      As for definitive chemoradiotherapy, cisplatin, 5-fluorouracil, and concurrent
      radiotherapy dosed to 50.4 Gy are used as standard treatment in a randomized
      clinical trial performed in North America. In patients who have T4 tumors and/or
      M1 lymph-node metastasis, chemoradiotherapy with cisplatin and 5-fluorouracil is
      considered standard treatment, but docetaxel, cisplatin, and 5-fluorouracil plus
      concurrent radiotherapy is also being studied. Controlled studies have not shown
      that palliative chemotherapy is superior to best supportive care, but cisplatin
      plus 5-fluorouracil is still considered standard therapy. Clinical trials of
      targeted agents are in progress. It is hoped that targeted agents will be
      effective for esophageal cancer.

PMID- 19742142
TI  - Maintenance Capecitabine for High-Risk Gastrointestinal Tumors: Everything That's
      Old Is New Again.

PMID- 19742143
TI  - Diabetes and PET Scans: Only Part of a Bigger Problem.

PMID- 19742144
TI  - 5-Fluorouracil-induced cardiotoxicity during chemotherapy for adenocarcinoma of
      the small bowel.

PMID- 19742145
TI  - Cetuximab for patients with colon cancer and hepatic metastasis complicated by
      liver dysfunction and icterus.

PMID- 19742146
TI  - Cutting the cost of cancer care.

PMID- 19742147
TI  - Michael Foster and Thomas Henry Huxley, Correspondence, 1865-1895.

PMID- 19742151
TI  - Ethanol consumption by Wistar rat dams affects selenium bioavailability and
      antioxidant balance in their progeny.
AB  - Ethanol consumption affects maternal nutrition, the mothers' antioxidant balance
      and the future health of their progeny. Selenium (Se) is a trace element cofactor
      of the enzyme glutathione peroxidase (GPx). We will study the effect of ethanol
      on Se bioavailability in dams and in their progeny. We have used three
      experimental groups of dams: control, chronic ethanol and pair-fed; and three
      groups of pups. Se levels were measured by graphite-furnace atomic absorption
      spectrometry. Serum and hepatic GPx activity was determined by spectrometry. We
      have concluded that ethanol decreased Se retention in dams, affecting their
      tissue Se deposits and those of their offspring, while also compromising their
      progeny's weight and oxidation balance. These effects of ethanol are caused by a
      reduction in Se intake and a direct alcohol-generated oxidation action.

PMID- 19742152
TI  - Door to door survey and community participation to implement a new county
      mosquito control program in Wayne County, North Carolina, USA.
AB  - Community involvement in mosquito management programs provides more sustainable
      and effective organization and service. A door to door survey in Wayne County, NC
      carried out by student volunteers, resulted in 60 household responses. Residents
      had not previously experienced outreach from the county (88%), and 95% of them
      thought the student door to door survey was an effective form of outreach. One
      third of the residents thought mosquitoes were severe where they lived, but only
      9% thought they had any containers in their yard that might breed mosquitoes.
      Only 15% of the residents were concerned about mosquito borne diseases. These
      responses provide evidence that outreach and education on mosquito control and
      diseases were necessary steps for future mosquito control community planning.

PMID- 19742153
TI  - Environmental effects on public health: an economic perspective.
AB  - In this article we critically review the economic literature on the effects of
      environmental changes on public health, in both the developed and the developing
      world. We first focus on the economic methodologies that are available for the
      evaluation of the effects (social costs and benefits) of environmental changes
      (degradation/preservation) on public health. Then, we explain how the monetary
      evaluations of these effects can feed back in the construction of economic policy
      for creating agent-specific incentives for more efficient public health
      management, which is also equitable and environmentally sustainable. Our
      exposition is accompanied by a synthesis of the available quantitative empirical
      results.

PMID- 19742154
TI  - Avoidable portion of tobacco-attributable acute care hospital days and its cost
      due to implementation of different intervention strategies in Canada.
AB  - The impact of four effective population-based interventions, focusing on
      individual behavioural change and aimed at reducing tobacco-attributable
      morbidity, was assessed by modeling with respect to effects on reducing
      prevalence rates of cigarette smoking, population-attributable fractions,
      reductions of disease-specific morbidity and its cost for Canada. Results
      revealed that an implementation of a combination of four tobacco policy
      interventions would result in a savings of 33,307 acute care hospital days, which
      translates to a cost savings of about $37 million per year in Canada. Assuming
      40% coverage rate for all individually based interventions, the two most
      effective interventions, in terms of avoidable burden due to morbidity, would be
      nicotine replacement therapy and physicians' advice, followed by individual
      behavioural counselling and increasing taxes by 10%. Although a sizable reduction
      in the number of hospital days and accumulated costs could be achieved, overall
      these interventions would reduce less than 3% of all tobacco-attributable costs
      in Canada.

PMID- 19742155
TI  - Time trend of the male proportion at birth in Brazil, 1979-2004.
AB  - Several studies suggest that exposure to environmental endocrine disrupters can
      reduce the number of male births, and therefore, the male proportion at birth
      (also denominated birth ratio or sex ratio at birth) can be used as a sentinel
      health indicator. This work aimed to analyze the trend of male births in Brazil,
      according to their distribution by states and capitals. An ecological descriptive
      time series was carried out using polynomial regression, showing a declining
      trend for male proportion at birth in Brazil (1979-1994), followed by an upward
      trend until 2004. A decline on the proportion of male births was observed in
      Brazil between 1979 and 1993, followed by a subsequent rise of this ratio between
      1995 and 2004, wherein the mean proportion of male births in Brazil rose from
      51.05 to 51.18, representing a relative increase of 0.25%. The states of Sao
      Paulo (Southwest region) and Acre (Western Amazon), as well as some capitals
      Cuiaba (Western Region), Palmas (Amazon) and Rio Branco (Amazon)-showed
      increasing trends, which suggests the influence of socio-demographic changes. In
      contrast, a declining trend in the State of Ceara State (Northeast region), with
      a 0.35% yearly decrease was observed. As a whole, these results suggest the
      influence of different environmental factors (demographic changes, public health
      services distribution, and population exposure to endocrine disruptor substances)
      influencing the time trend of birth ratio in the Brazilian population during the
      last decades.

PMID- 19742156
TI  - Verification of the addiction severity index Japanese version (ASI-J) as a
      treatment-customization, prediction, and comparison tool for alcohol-dependent
      individuals.
AB  - OBJECTIVE: To demonstrate the usefulness of the Addiction Severity Index Japanese
      Version (ASI-J) in Japanese alcohol-dependent individuals. The ASI is a
      frequently used clinical and research instrument that measures severities in
      seven functional domains in people with substance abuse disorders. METHODS: A
      total of 370 male inpatients with a history of alcohol dependence participated in
      the study. Forty-nine participants were excluded in the final analysis due to
      lack of reliability (i.e., patient misrepresentation or inability to understand).
      We used the ASI-J and a series of indexes that determined patient states during
      and post-treatment. RESULTS: The correlations between ASI Composite Scores (CSs),
      which were calculated through a weighted formula and indicated the severity of
      each problem area, were significant but low in eight relations and not
      significant in 13 relations, indicating substantial independence of the problem
      areas. Significant differences were found in Family/Social CSs between abstinent
      and relapsed alcohol-dependent individuals. The questions of undesirable attitude
      were significantly related to the CSs of Employment, Drug use, Family/Social, and
      Psychiatric sections. Significant differences were observed in patient
      demographics, CS, and ASI Severity Rating (SR) and interviewer's subjective
      scoring between alcohol-dependent individuals and drug abusers. CSs in Japanese
      alcohol-dependent individuals were generally similar to corresponding CSs in
      individuals from other countries, with the exception of The Netherlands.
      CONCLUSIONS: This study demonstrated that the ASI-J is useful for understanding
      individual profiles of problems for each patient and planning customized
      treatment. The ASI-J served as a predictive tool for relapse and compliance to
      treatment afterward and was shown to be useful as a comparison tool in clarifying
      similarities and differences between substance abuser groups.

PMID- 19742157
TI  - Plant-associated bacterial degradation of toxic organic compounds in soil.
AB  - A number of toxic synthetic organic compounds can contaminate environmental soil
      through either local (e.g., industrial) or diffuse (e.g., agricultural)
      contamination. Increased levels of these toxic organic compounds in the
      environment have been associated with human health risks including cancer. Plant
      associated bacteria, such as endophytic bacteria (non-pathogenic bacteria that
      occur naturally in plants) and rhizospheric bacteria (bacteria that live on and
      near the roots of plants), have been shown to contribute to biodegradation of
      toxic organic compounds in contaminated soil and could have potential for
      improving phytoremediation. Endophytic and rhizospheric bacterial degradation of
      toxic organic compounds (either naturally occurring or genetically enhanced) in
      contaminated soil in the environment could have positive implications for human
      health worldwide and is the subject of this review.

PMID- 19742158
TI  - Smoking determinants in Turkish university students.
AB  - The aim was to explore the prevalence and the correlates of smoking in a group of
      Turkish university students. A sample of 1,870 students (21.2 +/- 2.0 years old)
      completed the Beck Depression Inventory, Beck Hopelessness Scale, Anxiety
      Sensitivity Index, 20-item Toronto Alexithymia Scale. Smoking was highly
      prevalent (35.9%) in this sample. Male gender (OR = 2.72, CI 2.15-3.44), and
      parental smoking (OR = 1.41, CI 1.13-1.78) were factors associated with increased
      likelihood of smoking. Higher depressive symptoms and hopelessness levels were
      significantly related to smoking behavior. Smoking behavior might initiate as a
      mild and transient habit and unfortunately could become more serious and lead to
      an actual dependence. The results of this study show that it is necessary to pay
      attention to levels of depression and hopelessness, as well as parental
      influence.

PMID- 19742159
TI  - Chronic disease management in Sub-Saharan Africa: whose business is it?
AB  - Public health specialists and clinicians alike agree that Humanity faces a global
      pandemic of chronic diseases in the 21(st) century. In this article we discuss
      the implications of this pandemic on another global issue, the health workforce.
      Because both issues are particularly acute in Sub-Saharan Africa (SSA), we will
      focus on this region and use Cameroon as a case in point. We first gauge the
      epidemic of chronic conditions in SSA. We then discuss the implications of
      chronic conditions for the reshaping of health systems and the health workforce.
      We conclude by making a strong case for the building up and strengthening the
      health workforce, insisting on the crucial role of nurses, their training, and
      involvement in chronic disease management.

PMID- 19742160
TI  - The influence of socioeconomic and environmental determinants on health and
      obesity: a West Virginia case study.
AB  - A recursive system of ordered self assessed health together with BRFSS data were
      used to investigate health and obesity in the Appalachian state of West Virginia.
      Implications of unobserved heterogeneity and endogeneity of lifestyle outcomes on
      health were investigated. Obesity was found to be an endogenous lifestyle outcome
      associated with impaired health status. Risk of obesity is found to increase at a
      decreasing rate with per capita income and age. Intervention measures which
      stimulate human capital development, diet-disease knowledge and careful land use
      planning may improve health and obesity outcomes in Appalachia in particular and
      rural America in general.

PMID- 19742161
TI  - C-NMR assessment of the pattern of organic matter transformation during domestic
      wastewater treatment by autothermal aerobic digestion (ATAD).
AB  - The pattern of biodegradation and the chemical changes occurring in the
      macromolecular fraction of domestic sludge during autothermal thermophilic
      aerobic digestion (ATAD) was monitored and characterised via solid-state (13)C
      NMR CP-MAS. Major indexes such as aromaticity, hydrophobicity and alkyl/O-alkyl
      ratios calculated for the ATAD processed biosolids were compared by means of
      these values to corresponding indexes reported for sludges of different origin
      such as manures, soil organic matter and certain types of compost. Given that
      this is the first time that these techniques have been applied to ATAD sludge,
      the data indicates that long-chain aliphatics are easily utilized by the
      microbial populations as substrates for metabolic activities at all stages of
      aerobic digestion and serve as a key substrate for the temperature increase,
      which in turn results in sludge sterilization. The ATAD biosolids following
      treatment had a prevalence of O-alkyl domains, a low aromaticity index (10.4%)
      and an alkyl/O-alkyl ratio of 0.48 while the hydrophobicity index of the sludge
      decreased from 1.12 to 0.62 during the treatment. These results have important
      implications for the evolution of new ATAD modalities particularly in relation to
      dewatering and the future use of ATAD processed biosolids as a fertilizer,
      particularly with respect to hydrological impacts on the soil behaviour.

PMID- 19742162
TI  - Morphological deformities as biomarkers in fish from contaminated rivers in
      Taiwan.
AB  - Tilapia (Oreochromis spp.) were collected seasonally from four contaminated
      rivers in southwestern Taiwan for studies of morphological deformities that could
      be used as biomarkers of contamination. Morphological deformities found in
      tilapia were separated into 15 categories. Overall, the prevalence of deformities
      such as split fins, lower lip extension and gill deformities were significantly
      related to various water quality parameters, including low DO and high ammonium,
      lead and zinc concentrations. The persistence of tilapia in polluted waters and
      the development of a suite of morphological deformities suggest that tilapia can
      be used as sentinels of non-point source pollution in rivers.

PMID- 19742163
TI  - Tobacco smoke exposure and levels of urinary metals in the U.S. youth and adult
      population: the National Health and Nutrition Examination Survey (NHANES) 1999
      2004.
AB  - We assessed 12 urine metals in tobacco smoke-exposed and not exposed National
      Health and Nutrition Examination Survey participants. Our analysis included age,
      race/ethnicity, and poverty status. Gender and racial/ethnic differences in
      cadmium and lead and creatinine-adjusted and unadjusted data for group
      comparisons are presented. Smokers' had higher cadmium, lead, antimony, and
      barium levels than nonsmokers. Highest lead levels were in the youngest subjects.
      Lead levels among adults with high second-hand smoke exposure equaled smokers.
      Older smokers had cadmium levels signaling the potential for cadmium-related
      toxicity. Given the potential toxicity of metals, our findings complement
      existing research on exposure to chemicals in tobacco smoke.

PMID- 19742164
TI  - Connectivity for healthcare and well-being management: examples from six European
      projects.
AB  - Technological advances and societal changes in recent years have contributed to a
      shift in traditional care models and in the relationship between patients and
      their doctors/carers, with (in general) an increase in the patient-carer physical
      distance and corresponding changes in the modes of access to relevant care
      information by all groups. The objective of this paper is to showcase the
      research efforts of six projects (that the authors are currently, or have
      recently been, involved in), CAALYX, eCAALYX, COGKNOW, EasyLine+, I2HOME, and
      SHARE-it, all funded by the European Commission towards a future where citizens
      can take an active role into managing their own healthcare. Most importantly,
      sensitive groups of citizens, such as the elderly, chronically ill and those
      suffering from various physical and cognitive disabilities, will be able to
      maintain vital and feature-rich connections with their families, friends and
      healthcare providers, who can then respond to, and prevent, the development of
      adverse health conditions in those they care for in a timely manner, wherever the
      carers and the people cared for happen to be.

PMID- 19742165
TI  - Heavy metal hazards of pediatric syrup administration in Nigeria: a look at
      chromium, nickel and manganese.
AB  - Fifty different pediatric syrups were randomly sampled from patent medicine
      stores and pharmaceutical shops within Awka (Anambra State, Nigeria) between
      November 2007 and May 2008. Syrups were ashed before digestion using conc. aqua
      regia, HCl: HNO(3) (3:1). Chromium, nickel and manganese were assayed with AAS
      205A. The highest levels of nickel were seen in Magcid suspension (4.13 mg/L) and
      Gaviron (0.79 mg/L) whereas lowest levels were found in Asco-J vitamin and
      Jawaron Syrup (0.01 mg/L). About 44.1, 73.6 and 20.6% of the sampled syrups made
      in Nigeria had non detectable levels of nickel, chromium and manganese
      respectively. Chromium levels ranged from 0.01 mg/L in Magcid suspension to 0.58
      mg/L in emvite. Ferobin and Jawaron Syrup plus had 28.23 and 4.37 mg/L manganese,
      respectively. With the exception of Cephalexin Syrup, all the imported syrups had
      non detectable levels of chromium. The level of chromium in Cephalexin Syrup was
      0.01 mg/L. About 68.8 and 43.7% of these imported syrups had non-detectable
      levels of nickel and manganese respectively. Nickel levels ranged from 0.01-0.09
      mg/L in the imported syrups. Haemoglobin Syrup showed highest level of manganese
      of 0.36 mg/L whereas the lowest concentration was 0.02 mg/L in Cadiphen. Taken
      together the Nigerian made syrup samples had higher concentrations of the studied
      heavy metals. It is feared that ingestion of these syrups may constitute a
      significant source of heavy metal exposure to the children and should therefore
      be considered a public health problem. The public health hazards from ingestion
      of these syrups should be identified and disclosed by in-depth risk assessment
      studies.

PMID- 19742166
TI  - Epistasis between IL1A, IL1B, TNF, HTR2A, 5-HTTLPR and TPH2 variations does not
      impact alcohol dependence disorder features.
AB  - We assessed a set of biological (HDL, LDL, SGOT, SGPT, GGT, HTc, Hb and T levels)
      and psychometric variables (investigated through HAM-D, HAM-A, GAS, Liebowitz
      Social Anxiety Scale, Mark & Mathews Scale, Leyton scale, and Pilowski scale) in
      a sample of 64 alcohol dependent patients, at baseline and after a detoxification
      treatment. Moreover, we recruited 47 non-consanguineous relatives who did not
      suffer alcohol related disorders and underwent the same tests. In both groups we
      genotyped 11 genetic variations (rs1800587; rs3087258; rs1799724; 5-HTTLPR;
      rs1386493; rs1386494; rs1487275; rs1843809; rs4570625; rs2129575; rs6313) located
      in genes whose impact on alcohol related behaviors and disorders has been
      hypothesized (IL1A, IL1B, TNF, 5-HTTLPR, TPH2 and HTR2A). We analyzed the
      epistasis of these genetic variations upon the biological and psychological
      dimensions in the cases and their relatives. Further on, we analyzed the effects
      of the combined genetic variations on the short - term detoxification treatment
      efficacy. Finally, being the only not yet investigated variation within this
      sample, we analyzed the impact of the rs6313 alone on baseline assessment and
      treatment efficacy. We detected the following results: the couple rs6313 +
      rs2129575 affected the Leyton -Trait at admission (p = 0.01) (obsessive
      compulsive trait), whilst rs1800587 + 5-HTTLPR impacted the Pilowski test at
      admission (p = 0.01) (hypochondriac symptoms). These results did not survive
      Bonferroni correction (p < or = 0.004). This lack of association may depend on
      the incomplete gene coverage or on the small sample size which limited the power
      of the study. On the other hand, it may reflect a substantial absence of
      relevance of the genotype variants toward the alcohol related investigated
      dimensions. Nonetheless, the marginal significance we detected could witness an
      informative correlation worth investigating in larger samples.

PMID- 19742167
TI  - Prevalence of alcohol consumption and hazardous drinking, tobacco and drug use in
      urban Tanzania, and their associated risk factors.
AB  - Evidence suggests substance abuse in Tanzania is a growing public health problem.
      A random sample of 899 adults aged 15-59 in two urban sites of differing levels
      of poverty surveyed alcohol, tobacco and illicit substance use. Rates of
      substance use were 17.2%. 8.7% and 0.8% for alcohol, tobacco and cannabis,
      respectively. Living in the less affluent area was associated with higher
      lifetime rates of tobacco and alcohol use. Substance use is less prevalent in
      Tanzania than in richer countries, but lifetime consumption is higher in poorer
      areas. The association of substance use with a range of socio-economic factors
      warrants further research.

PMID- 19742168
TI  - Silent trace eliminates differential eyeblink learning in abstinent alcoholics.
AB  - Chronic alcoholism has profound effects on the brain, including volume reductions
      in regions critical for eyeblink classical conditioning (EBCC). The current study
      challenged abstinent alcoholics using delay (n = 20) and trace (n = 17)
      discrimination/reversal EBCC. Comparisons revealed a significant difference
      between delay and trace conditioning performance during reversal (t (35) = 2.08,
      p < 0.05). The difference between the two tasks for discrimination was not
      significant (p = 0.44). These data support the notion that alcoholics are
      increasingly impaired in the complex task of reversing a previously learned
      discrimination when a silent trace interval is introduced. Alcoholics' impairment
      in flexibly altering learned associations may be central to their continued
      addiction.

PMID- 19742169
TI  - Ecological sustainability: what role for public health education?
AB  - This article explores the notion of ecological sustainability in the context of
      public health education and the contribution Universities can make in creating
      environments that include ecologically sustainable practices. It considers the
      important role of environmental health in building a sustainable future for the
      population as a central plank of public health. It presents the evidence for the
      need for comprehensive approaches to ecological sustainability within the
      University and offers suggestions about how this can take place. It concludes by
      arguing that to date there is a substantial gap between the rhetoric and the
      reality in the University context.

PMID- 19742170
TI  - The effects of environmental factors on persons living with HIV/AIDS.
AB  - In recent years, environmental awareness has received a great deal of public
      attention. However, little emphasis has been put on the influence of
      environmental factors (weather, personal attitudes, policies, physical
      structures, transportation, etc.) on the quality of life of persons infected with
      HIV/AIDS. The goal of this study was to assess the effect of selected
      environmental factors on the quality of life of persons affected by HIV/AIDS. To
      achieve this goal, the Craig Hospital Inventory of Environmental Factors (CHIEF)
      subscales including Policies, Physical Structure, Work/School, Attitudes/Support,
      and Service/Assistance were evaluated in patients selected from a STD/HIV clinic
      in Jackson, MS. They were chosen based on previously diagnosed HIV/AIDS status
      and age (16-95). Written consents, demographics sheets and self-administered
      questionnaires were obtained. Data were analyzed using Excel and SPSS software.
      Interviews started in July 2007 and ended in August, 2007. One hundred and
      thirteen patients responded. Participants were 72.6% (82) male, 26.5% (30) female
      and 0.9% (1) transgender. The median age of participants was 38.8 (18-63). Over
      50% (65) had some college or higher education, and 35.4% reported annual incomes
      less than $10,000. Multivariate analysis showed marginal significance between
      disease diagnosis and gender (p < 0.10), and statistical significance between
      disease diagnosis and income (p = 0.03). Also, age (p = 0.01) and education (p =
      0.03) were significant predictors in one of the subscales. The CHIEF subscales
      that showed the greatest significance among AIDS respondents were Attitudes and
      Support, and Government Policies with mean sensitivity scores of 1.39 and 1.42,
      respectively. The element with the least effect on AIDS patients was the
      Work/School subscale, with a mean score of 0.74. In general AIDS patients were
      disproportionately affected in all but one of the five subscales observed.
      Conversely those with HIV were more affected in the Work/School subscale with a
      mean score of 1.70. This proved to be the only subscale responsible for causing
      the greatest degree of perceived barriers for the HIV population. With a mean
      score of 0.75, Physical/Structural subscale showed the least negative impact on
      those infected HIV without AIDS. It is therefore recommended that the
      environmental barriers identified in this study be addressed in order to
      eliminate/minimize their negative effect and improve the quality of life of
      HIV/AIDS patients.

PMID- 19742171
TI  - The liver-brain axis of alcohol-mediated neurodegeneration: role of toxic lipids.
AB  - Alcohol abuse causes progressive toxicity and degeneration in liver and brain due
      to insulin resistance, which exacerbates oxidative stress and pro-inflammatory
      cytokine activation. Alcohol-induced steatohepatitis promotes synthesis and
      accumulation of ceramides and other toxic lipids that cause insulin resistance.
      Ceramides can readily cross the blood-brain barrier, and ceramide exposure causes
      neurodegeneration with insulin resistance and oxidative stress, similar to the
      effects of alcohol. Therefore, in addition to its direct neurotoxic effects,
      alcohol misuse establishes a liver-brain axis of neurodegeneration mediated by
      toxic lipid trafficking across the blood-brain barrier, leading to progressive
      white matter degeneration and cognitive impairment.

PMID- 19742172
TI  - The relationship between concurrent substance use disorders and eating disorders
      with personality disorders.
AB  - OBJECTIVE: The current pilot study investigated whether patients with concurrent
      substance use disorders and eating disorders (SUD and ED) who experienced a
      reduction in SUD and ED symptoms following treatment for SUD and ED also
      experienced a reduction in personality disorder (PD) symptoms. METHOD: Twenty
      patients with SUD and ED and PD were assessed pre and post treatment using
      clinical interviews, self-report questionnaires, and a therapist questionnaire on
      DSM-IV-TR symptoms for PD. RESULTS: Symptoms for the personality disorders were
      reduced following treatment. This reduction was correlated with a decrease in the
      number of symptoms of ED at post treatment. DISCUSSION: Chronic concurrent SUD
      and ED may make it difficult to separate PD symptoms from co-occurring disorders.
      Many features attributed to PDs may be reduced when problematic substance use and
      disordered eating are addressed, a fact that may increase clinician and
      patients'optimism about therapeutic change.

PMID- 19742173
TI  - Thermodynamics of surfactants, block copolymers and their mixtures in water: the
      role of the isothermal calorimetry.
AB  - The thermodynamics of conventional surfactants, block copolymers and their
      mixtures in water was described to the light of the enthalpy function. The two
      methodologies, i.e. the van't Hoff approach and the isothermal calorimetry, used
      to determine the enthalpy of micellization of pure surfactants and block
      copolymers were described. The van't Hoff method was critically discussed. The
      aqueous copolymer+surfactant mixtures were analyzed by means of the isothermal
      titration calorimetry and the enthalpy of transfer of the copolymer from the
      water to the aqueous surfactant solutions. Thermodynamic models were presented to
      show the procedure to extract straightforward molecular insights from the bulk
      properties.

PMID- 19742174
TI  - Co-localization of carbonic anhydrase and phosphoenol-pyruvate carboxylase and
      localization of pyruvate kinase in roots and hypocotyls of etiolated Glycine max
      seedlings.
AB  - We investigated the presence of carbonic anhydrase in root and hypocotyl of
      etiolated soybean using enzymatic, histochemical, immunohistochemical and in situ
      hybridization approaches. In parallel, we used in situ hybridization and
      immunolocalization to determine the expression pattern and localization of
      phosphoenolpyruvate carboxylase. Their co-localization in the root tip as well as
      in the central cylinder, suggests that a large fraction of the CO(2) may be re
      introduced into C4 compounds. GmPK3 expression, coding for a cytoplasmic isoform
      of pyruvate kinase, was detected in all different root cell types, suggesting
      that both phosphoenolpyruvate-utilizing enzymes are involved in
      phosphoenolpyruvate metabolism in etiolated soybean roots; a case indicative of
      the necessary flexibility plant metabolism has to adopt in order to compensate
      various physiological conditions.

PMID- 19742175
TI  - Heats of mixing using an isothermal titration calorimeter: associated thermal
      effects.
AB  - The correct determination of the energy generated or absorbed in the sample cell
      of an Isothermal Titration Calorimeter (ITC) requires a thorough analysis of the
      calorimetric signal. This means the identification and quantification of any
      thermal effect inherent to the working method. In this work, it is carried out a
      review on several thermal effects, studied by us in previous work, and which
      appear when an ITC is used for measuring the heats of mixing of liquids in a
      continuous mode. These effects are due to: (i) the difference between the
      temperature of the injected liquid and the temperature of the mixture during the
      mixing process, (ii) the increase of the liquid volume located in the mixing cell
      and (iii) the stirring velocity. Besides, methods for the identification and
      quantification of the mentioned effects are suggested.

PMID- 19742176
TI  - The dimeric proto-ribosome: Structural details and possible implications on the
      origin of life.
AB  - A symmetric pocket-like entity, composed of two L-shaped RNA units, encircles the
      peptide synthesis site within the contemporary ribosome. This entity was
      suggested to be the vestige of a dimeric proto-ribosome, which could have formed
      spontaneously in the prebiotic world, catalyzing non-coded peptide bond formation
      and elongation. This structural element, beyond offering the initial step in the
      evolution of translation, is hypothesized here to be linked to the origin of
      life. By catalyzing the production of random peptide chains, the proto-ribosome
      could have enabled the formation of primary enzymes, launching a process of co
      evolution of the translation apparatus and the proteins, thus presenting an
      alternative to the RNA world hypothesis.

PMID- 19742178
TI  - Characterization and purification of polydisperse reconstituted lipoproteins and
      nanolipoprotein particles.
AB  - Heterogeneity is a fact that plagues the characterization and application of many
      self-assembled biological constructs. The importance of obtaining particle
      homogeneity in biological assemblies is a critical goal, as bulk analysis tools
      often require identical species for reliable interpretation of the results
      indeed, important tools of analysis such as x-ray diffraction typically require
      over 90% purity for effectiveness. This issue bears particular importance in the
      case of lipoproteins. Lipid-binding proteins known as apolipoproteins can self
      assemble with liposomes to form reconstituted high density lipoproteins (rHDLs)
      or nanolipoprotein particles (NLPs) when used for biotechnology applications such
      as the solubilization of membrane proteins. Typically, the apolipoprotein and
      phospholipids reactants are self assembled and even with careful assembly
      protocols the product often contains heterogeneous particles. In fact, size
      polydispersity in rHDLs and NLPs published in the literature are frequently
      observed, which may confound the accurate use of analytical methods. In this
      article, we demonstrate a procedure for producing a pure, monodisperse NLP
      subpopulation from a polydisperse self-assembly using size exclusion
      chromatography (SEC) coupled with high resolution particle imaging by atomic
      force microscopy (AFM). In addition, NLPs have been shown to self assemble both
      in the presence and absence of detergents such as cholate, yet the effects of
      cholate on NLP polydispersity and separation has not been systematically
      examined. Therefore, we examined the separation properties of NLPs assembled in
      both the absence and presence of cholate using SEC and native gel
      electrophoresis. From this analysis, NLPs prepared with and without cholate
      showed particles with well defined diameters spanning a similar size range.
      However, cholate was shown to have a dramatic affect on NLP separation by SEC and
      native gel electrophoresis. Furthermore, under conditions where different sized
      NLPs were not sufficiently separated or purified by SEC, AFM was used to
      deconvolute the elution pattern of different sized NLPs. From this analysis we
      were able to purify an NLP subpopulation to 90% size homogeneity by taking
      extremely fine elutions from the SEC. With this purity, we generate high quality
      NLP crystals that were over 100 microm in size with little precipitate, which
      could not be obtained utilizing the traditional size exclusion techniques. This
      purification procedure and the methods for validation are broadly applicable to
      other lipoprotein particles.

PMID- 19742177
TI  - Applications of isothermal titration calorimetry in biophysical studies of G
      quadruplexes.
AB  - G-quadruplexes are higher-order nucleic acids structures formed by G-rich
      sequences that are stabilized by tetrads of hydrogen-bonded guanine bases.
      Recently, there has been growing interest in the study of G-quadruplexes because
      of their possible involvement in many biological processes. Isothermal titration
      calorimetry (ITC) has been proven to be a useful tool to study the energetic
      aspects of G-quadruplex interactions. Particularly, ITC has been applied many
      times to determine the thermodynamic properties of drug-quadruplex interactions
      to screening among various drugs and to address drug design. In the present
      review, we will focus on the ITC studies of G-quadruplex structures and their
      interaction with proteins and drugs and the most significant results will be
      discussed.

PMID- 19742179
TI  - Hyaluronan benzyl ester as a scaffold for tissue engineering.
AB  - Tissue engineering is a multidisciplinary field focused on in vitro
      reconstruction of mammalian tissues. In order to allow a similar three
      dimensional organization of in vitro cultured cells, biocompatible scaffolds are
      needed. This need has provided immense momentum for research on "smart scaffolds"
      for use in cell culture. One of the most promising materials for tissue
      engineering and regenerative medicine is a hyaluronan derivative: a benzyl ester
      of hyaluronan (HYAFF). HYAFF can be processed to obtain several types of devices
      such as tubes, membranes, non-woven fabrics, gauzes, and sponges. All these
      scaffolds are highly biocompatible. In the human body they do not elicit any
      adverse reactions and are resorbed by the host tissues. Human hepatocytes, dermal
      fibroblasts and keratinocytes, chondrocytes, Schwann cells, bone marrow derived
      mesenchymal stem cells and adipose tissue derived mesenchymal stem cells have
      been successfully cultured in these meshes. The same scaffolds, in tube meshes,
      has been applied for vascular tissue engineering that has emerged as a promising
      technology for the design of an ideal, responsive, living conduit with properties
      similar to that of native tissue.

PMID- 19742180
TI  - Organic analysis of peridotite rocks from the Ashadze and Logatchev hydrothermal
      sites.
AB  - This article presents an experimental analysis of the organic content of two
      serpentinized peridotite rocks of the terrestrial upper mantle. The samples have
      been dredged on the floor of the Ashadze and Logatchev hydrothermal sites on the
      Mid-Atlantic Ridge. In this preliminary analysis, amino acids and long chain n
      alkanes are identified. They are most probably of biological/microbial origin.
      Some peaks remain unidentified.

PMID- 19742181
TI  - Episodic confusional state: Due to insulinoma.
AB  - This case report deals with 45-year-old male who came for consultation in the
      psychiatry department for the persisting symptoms, after consulting various
      departments with no relief. He had episodes of confusion with disorganized
      behavior, restlessness, and symptoms like talking irrelevantly once a week
      lasting up to 10-30 min in the preceding six months. Investigations like
      computerized tomography scan, electroencephalogram were not contributory. While
      under observation in our ward for evaluation and diagnosis, one such episode with
      intense sweating and clouding of consciousness was witnessed and helped in
      clinching the diagnosis of insulinoma. The case is reported for its rarity and as
      one of the causes of episodic confusional state.

PMID- 19742182
TI  - Intentional self-harm seen in psychiatric referrals in a tertiary care hospital.
AB  - BACKGROUND: Intentional self-harm is common, through out the world; however,
      there is scanty data from India. AIMS: To study the sociodemographic and clinical
      profile of subjects with "intentional self-harm" referred to consultation-liaison
      psychiatric services for evaluation in a tertiary care hospital. DESIGN:
      Retrospective chart review. MATERIALS AND METHODS: For this study, the
      consultation-liaison register of Department of Psychiatry was screened to obtain
      data of all patients who were referred to psychiatry referral services and were
      diagnosed as "intentional self-harm" while they were admitted in Nehru Hospital,
      Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh
      during the period of 2000-2005. The case notes of these patients were reviewed
      for obtaining the sociodemographic profile and clinical profile for the current
      study. RESULTS: Majority of the subjects were married (61%), educated beyond
      matriculation (75%), were employed or retired (53.6%), belonged to Hindu (87%),
      nuclear family (64.5%) of middle socioeconomic status (85%) and came from urban
      background (53%). Most common reasons/precipitating events prior to intentional
      self-harm were interpersonal problems with family members (39.2%), followed by
      interpersonal problems with spouse (16.9%). The most common method of intentional
      self-harm used was consumption of insecticides (44.6%), followed by use of
      corrosives (17.5%). Half of the sample (48.2%) did not fulfill criteria for any
      axis-1 or axis-2 psychiatric diagnosis at the time of assessment and most common
      psychiatric diagnosis was depression (30.7 %). CONCLUSIONS: Nearly half of the
      subjects who present to a tertiary care hospital with intentional self-harm do
      not have diagnosable psychiatric illness.

PMID- 19742183
TI  - Continuing medical education.

PMID- 19742184
TI  - Analysis of the role of human leukocyte antigen class-I genes to understand the
      etiopathology of schizophrenia.
AB  - BACKGROUND: Schizophrenia is the paradigmatic illness of psychiatry. The
      involvement of immunological and immunopathological mechanisms in the
      etiopathogenesis of schizophrenia has been a matter of research, with recently
      increasing effort. AIMS: In this study, we investigated the incidence of human
      leukocyte antigen (HLA) Class I antigens to understand the role of HLA genes in
      schizophrenia. MATERIALS AND METHODS: India born schizophrenic patients in and
      around Siliguri who attended outpatient department (OPD) of Department of
      Psychiatry, North Bengal Medical College and Hospital were considered for the
      present study. After the longitudinal follow up, 50 patients were enrolled for
      the study. The same number of age, sex and ethnically matched healthy subjects
      were considered as control. Low resolution polymerase chain reaction-sequence
      specific primer method was applied for typing the HLA antigens. STATISTICS: The
      phenotype frequencies were calculated by direct count. chi(2) test was done to
      compare the frequency of each antigen among the patients and control group and it
      was followed by Fisher's exact test. Relative risk was estimated by using
      Haldane's method. RESULTS: The result showed that some of the HLA antigens are
      associated with the schizophrenia and significant increase were observed for HLA
      A*03 antigen along with the significant decrease for HLA A*25, A*31 and HLA B*51.
      CONCLUSIONS: The study provides the evidence for the possible existence of
      susceptibility locus for schizophrenia within the HLA region. This preliminary
      observation may help to understand the etiological basis of this disorder and the
      study may further strengthen the HLA antigens as the marker for schizophrenia.

PMID- 19742185
TI  - Telling the truth to patients and relatives.

PMID- 19742186
TI  - Comparative study of personality disorder associated with deliberate self harm in
      two different age groups (15-24 years and 45-74 years).
AB  - AIMS: To study the presence of personality disorder in cases of deliberate self
      harm (DSH) in young (15-24 years) and elderly (45-74 years) and compare.
      MATERIALS AND METHODS: Deliberate self harm cases admitted in Medical and
      surgical departments and cases attending psychiatry department of R.G. Kar
      Medical College, Kolkata were studied. For diagnosis of personality disorder ICD
      10 International Personality Disorder Examination (IPDE) questionnaire was used.
      RESULTS: Percentage of elderly patients having personality disorder (64%) was
      higher compared to young DSH patients (58.5%). In young group, most common
      disorder was emotionally unstable personality disorder (28.6%) and in elderly
      group most common was anankastic type of personality disorder (36%). Schizoid,
      dissocial, histrionic, and anxious-avoidant personality disorders were found in
      small percentages of cases. CONCLUSION: Among DSH patients, the most common
      personality disorder found in young age was Emotionally unstable (Impulsive and
      Borderline) personality disorder, but most common personality disorder found in
      elderly patients was Anankastic personality disorder.

PMID- 19742187
TI  - A comparative study of oxidative stress and interrelationship of important
      antioxidants in haloperidol and olanzapine treated patients suffering from
      schizophrenia.
AB  - CONTEXT: Oxidative stress induced lipid peroxidation has been a significant
      contributing factor for schizophrenia. Older antipsychotics, like haloperidol ,
      were found to increase lipid peroxidation, whereas, the newer atypical
      antipsychotics, like olanzapine, did not generate free radicals as metabolic end
      products. AIMS: The interrelationship of the antioxidant vitamins and antioxidant
      enzymes, and their overall effect on regulation of oxidative stress induced by
      haloperidol as compared to olanzapine were analyzed in present study. SETTING AND
      DESIGN: It was an open randomized cross sectional study that consisted of two
      groups of fifty schizophrenic patients treated by haloperidol and olanzapine,
      respectively for at least six months. MATERIALS AND METHODS: Serum thiobarbituric
      acid reacting substances (TBARS) was selected as marker of lipid peroxidation,
      whereas, serum tocopherols, plasma ascorbate and plasma superoxide dismutase
      (SOD) activity, were selected to assess the antioxidant vitamin and antioxidant
      enzyme status, respectively. All measurements were done by standard photometric
      methods. STATISTICAL ANALYSIS USED: Statistical analysis was performed to find
      out the significance for the differences of means between two groups. Bivariate
      and partial correlation coefficients for assessing the interrelationship between
      different parameters were done by using statistical package for social sciences
      (SPSS) software. RESULTS: Results showed significantly higher serum TBARS and
      lower antioxidant values in the haloperidol treated patients. Significant
      positive correlations among the individual antioxidant parameters and significant
      negative correlation between all of the antioxidant parameters and serum TBARS
      were found only in haloperidol treated patients. Plasma SOD activity correlated
      to plasma ascorbate in both groups. Partial correlation results revealed that the
      serum tocopherol decreased linearly with an increase in serum TBARS significantly
      in olanzapine treated patients when effect of plasma ascorbate was controlled.
      CONCLUSIONS: Haloperidol caused more oxidative stress along with a significant
      reduction of important antioxidant parameters. Plasma ascorbate was found to be
      the chief antioxidant on which the activity of both plasma SOD and alpha
      tocopherol were dependent under oxidative stressful conditions.

PMID- 19742188
TI  - Faking it - II: Countering and preventing counterfeiting of drugs.

PMID- 19742189
TI  - Reporting ethical aspects in published research articles in the Indian Journal of
      Psychiatry.
AB  - BACKGROUND: Reporting of informed consent and ethical approval are important
      aspects of published papers which indicate the knowledge and sensitivity about
      ethical aspects of research by the researchers. MATERIALS AND METHODS: This study
      reports description of informed consent and ethical approval in the published
      psychiatric research in the main journal of psychiatry in India. All original
      research articles (n=157) published in the Indian Journal of Psychiatry in the
      years 2000, 2003 to 2007 were included. RESULTS: Informed consent was mentioned
      in 51% of studies in 2000, which gradually rose to 82% by the year 2007. Ethics
      committee approvals were mentioned in 2% of studies in 2000, and 25% of reports
      in 2007. Consent was reported to be written in only 40%, content of the consent
      forms was mentioned in 17%, and the language of consent form was reported in 3%
      of the studies where consent was reported. CONCLUSIONS: Regulation of ethical
      principles and formulation of necessary guidelines or rules for research as well
      as for publications are necessary and desirable to ensure the safety of
      participants and good quality of research.

PMID- 19742191
TI  - Dementia clinic in general hospital settings.
AB  - BACKGROUND: There is a need to develop specialised dementia care services in
      developing countries. MATERIALS AND METHODS: We used the existing infrastructure
      of a general hospital to start a weekly dementia clinic. RESULTS: We were able to
      support home-based care, even in patients with advanced disease. This new service
      gave us opportunity to train clinicians and researchers interested in dementia.
      CONCLUSION: It is feasible to start weekly dementia clinics using existing
      infrastructure in developing countries. Networking of such centres can generate a
      database capable of guiding service development.

PMID- 19742190
TI  - The prevention and treatment of cognitive decline and dementia: An overview of
      recent research on experimental treatments.
AB  - The prevention and treatment of cognitive impairment in the elderly has assumed
      increasing importance in an aging population. This article presents a qualitative
      review of recent research on experimental interventions for the prevention and
      treatment of mild cognitive impairment and Alzheimer's disease in elderly
      subjects. Interventions addressed range from lifestyle measures to
      pharmacological treatments. Epidemiological studies suggest that dietary
      measures, physical exercise, and mental activity may reduce the risk of cognitive
      impairment and Alzheimer's disease in elderly subjects. Statins may protect
      against incident dementia, and lithium may convey similar benefits to bipolar
      patients. Ginkgo appears ineffective as a primary preventive measure. Donepezil
      but not Vitamin E may benefit persons with mild cognitive impairment.
      Experimental treatments potentially useful for Alzheimer's disease include
      dimebon, PBT2 and etanercept; the safety and efficacy of the Alzheimer's vaccine
      remains to be proven, and growth hormone secretagogue and tarenflurbil are likely
      ineffective. Herbal treatments merit study in elderly subjects with cognitive
      syndromes.

PMID- 19742192
TI  - Transgenderism: Facts and fictions.
AB  - The nosology associated with transgender phenomena is undergoing rapid revisions.
      This phenomenon is mentioned in ancient cultures and the allusions to it are
      variously described in the Indian literatures. The trials and tribulations of the
      isolated segment of the human population are surmised from two autobiographical
      accounts of writers. The measures to improve the life of the transgender
      population are suggested.

PMID- 19742193
TI  - Neurobiology of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a devastating neurodegenerative disease, the most
      common among the dementing illnesses. The neuropathological hallmarks of AD
      include extracellular beta-amyloid (amyloid precursor protein (APP) deposits,
      intracellular neurofibrillary tangles (NFT)), dystrophic neuritis and amyloid
      angiopathy. The mismetabolism of APP and the defective clearance of beta amyloid
      generate a cascade of events including hyperphosphorylated tau (tau) mediated
      breakdown of microtubular assembly and resultant synaptic failure which results
      in AD. The exact aetiopathogenesis of AD is still obscure. The preeminent
      hypotheses of AD include amyloid cascade hypothesis and tau hyperphosphorylation.
      The amyloid hypothesis states that extracellular amyloid plaques formed by
      aggregates of Abeta peptide generated by the proteolytic cleavages of APP are
      central to AD pathology. Intracellular assembly states of the oligomeric and
      protofibrillar species may facilitate tau hyperphosphorylation, disruption of
      proteasome and mitochondria function, dysregulation of calcium homeostasis,
      synaptic failure, and cognitive dysfunction. The tau hypothesis states that
      excessive or abnormal phosphorylation of tau results in the transformation of
      normal adult tau into PHF-tau (paired helical filament) and NFTs. Vascular
      hypothesis is also proposed for AD and it concludes that advancing age and the
      presence of vascular risk factors create a Critically Attained Threshold of
      Cerebral Hypoperfusion (CATCH) which leads to cellular and subcellular pathology
      involving protein synthesis, development of plaques, inflammatory response, and
      synaptic damage leading to the manifestations of AD. Multiple other aetiological
      and pathogenetic hypotheses have been put forward including genetics, oxidative
      stress, dysfunctional calcium homeostasis, hormonal, inflammatory-immunologic,
      and cell cycle dysregulation with the resultant neurotransmitter dysfunctions and
      cognitive decline. The available therapeutic agents target only the
      neurotransmitter dysfunction in AD and agents specifically targeting the
      pathogenetic mechanisms like amyloid deposition and tau hyperphosphorylation
      might provide a definite therapeutic edge.

PMID- 19742194
TI  - Finding my faith.

PMID- 19742195
TI  - Can bupropion unmask psychosis.
AB  - Bupropion is an antidepressant, which has recently been promoted for the
      treatment of bipolar depression, because of its lower potency to induced switch.
      However, due to its dopamine enhancing effect, it has been reported to induce
      psychosis and perceptual changes. Most of the literature, which is available in
      relation to development of psychosis while receiving bupropion, has been with the
      use of immediate release formulation. Some of the case report which have reported
      development of psychosis with sustained release Bupropion, it has been reported
      in the background history of over dosage or substance abuse. We present case in
      which use of bupropion led to development of frank psychosis, which responded to
      use of antipsychotic medication. However, when antipsychotics were stopped,
      psychosis again recurred and as a result diagnosis of patient was changed.

PMID- 19742196
TI  - Mean and variability of QT-interval: Relevance to psychiatric illness and
      psychotropic medication.

PMID- 19742197
TI  - Expect more from us...

PMID- 19742198
TI  - Teratogenicity and hyperprolactinemia.

PMID- 19742199
TI  - Is a single editorial sufficient?

PMID- 19742200
TI  - Comments: The doctor's dilemma: Truth telling.

PMID- 19742201
TI  - Behavioral and psychological symptoms of dementia: A study of symptomatology.
AB  - BACKGROUND: Behavioral disturbances are integral to the dementing process and
      contribute adversely to the quality of life of the patients and caregivers.
      Information regarding the nature of symptoms in Alzheimer's disease is limited in
      the Indian context. AIM: To study the nature of symptoms in Alzheimer's disease
      using the Malayalam adaptation of Behavioral Pathology in Alzheimer's disease
      Rating Scale (BEHAVE-AD). MATERIALS AND METHODS: Forty patients diagnosed as
      having Alzheimer's disease as per DSM-IV criteria were studied using the
      Malayalam version of BEHAVE-AD. RESULTS: Delusions and paranoid ideations were
      present in 53% of the sample studied and 33% had hallucinations. Activity
      disturbances were seen in 65%, aggressive symptoms in 75% and diurnal rhythm
      disturbances in 55%. Affective disturbances and anxiety symptoms were present in
      37% and 43% respectively. CONCLUSION: The prevalence of behavioral and
      psychological symptoms of dementia was found to be high.

PMID- 19742202
TI  - Consanguinity: Still a challenge.

PMID- 19742203
TI  - Hypertensive crisis and cheese.

PMID- 19742204
TI  - Relationship between consanguinity and depression in a south Indian population.
AB  - A Pilot study was Carried out to study the association of consanguinity marriage
      with depression. It was observed that the consanguinity of marriage was
      associated with depression. The odds ratio was 5.66 (CI: 2.42-13.54). The age and
      sex had an association with depression. The age and sex adjusted odds ratio of
      consanguinity marriage was 7.66 (CI: 3.93-19.45) indicating that it is
      independently associated with depression.

PMID- 19742205
TI  - More questions than answers! Clinical dilemmas in psychopharmacology in pregnancy
      and lactation.
AB  - Women in childbearing age frequently suffer from mental illness. Maternal
      psychiatric disorders may have a devastating impact on the fetus and the newborn.
      Thus treating or preventing relapse of these disorders during pregnancy and
      puerperium is a clinical and ethical duty with the necessity to avoid or minimize
      fetal or neonatal drug exposure. Though there are many guidelines and
      comprehensive reviews regarding drug safety in pregnancy and lactation, the
      application of these recommendations into clinical practice appears to be
      complex. Hence, we present some clinical questions with answers considering the
      available literature on safety of psychotropics in pregnancy and lactation.

PMID- 19742207
TI  - Serotonin syndrome associated with sertraline, trazodone and tramadol abuse.

PMID- 19742206
TI  - Behavioral symptoms and caregiver burden in dementia.
AB  - BACKGROUND: Dementia care in developing countries will continue to be provided by
      co-resident caregivers at home. Behavioral and Psychological Symptoms of Dementia
      (BPSD) are difficult to manage at home. Interventions leading to reduction or
      remission of reduction or remission of BPSD will be of immense help in the
      management of these patients. MATERIALS AND METHODS: The nature and prevalence of
      BPSD in a community sample of patients with dementia was assessed by a clinician.
      The impact of these symptoms on the caregiver was assessed by measures of burden
      of care and the psychological well being of the caregiver. Another rater carried
      out these assessments independently. RESULTS: Prevalence of BPSD was very high
      and they were more common in patients with Alzheimer's Disease than patients with
      Vascular Dementia. They were rated as troubling to most caregivers. Caregiver
      burden was associated with adverse effects on the mental health of the carer.
      CONCLUSIONS: To be effective, dementia care services in developing countries need
      to focus on management of BPSD at home. Development of a low cost, effective and
      sustainable dementia care service should be given due importance by the policy
      makers in the developing world.

PMID- 19742208
TI  - The quality of alcohol products in Vietnam and its implications for public
      health.
AB  - Four homemade (artisanally manufactured and unrecorded) and seven commercial
      (industrially manufactured and taxed) alcohol products from Vietnam were
      collected and chemically analyzed for toxicologically relevant substances. The
      majority of both types had alcohol contents between 30 and 40% vol. Two homemade
      samples contained significantly higher concentrations of 45 and 50% vol. In one
      of these homemade samples the labeled alcoholic strength was exceeded by nearly
      20% vol. All other analyzed constituents of the samples (e.g., methanol,
      acetaldehyde, higher alcohols, esters, metals, anions) were found in
      concentrations that did not pose a threat to public health. A peculiarity was a
      homemade sample of alcohol with pickled snakes and scorpions that contained 77%
      vol of alcohol, allegedly used as traditional Chinese medicine. Based on this
      small sample, there is insufficient evidence to conclude that alcohol quality,
      beyond the effects of ethanol, has an influence on health in Vietnam. However,
      future research with larger samples is needed.

PMID- 19742209
TI  - Neighborhood environment and self-rated health among adults in Southern Sri
      Lanka.
AB  - The prevalence of different neighborhood environmental stressors and associations
      between the stressors and self-rated health are described in a representative
      sample of 2,077 individuals, aged 18-85 years, in southern Sri Lanka. Mosquito
      menace (69.4%), stray dog problems (26.8%), nuisance from neighbors (20.3%), and
      nuisance from drug users (18.7%) were found to be the most prevalent
      environmental stressors. None of the stressors investigated were associated with
      self-rated physical health, but nuisance from neighbors, nuisance from drug
      users, shortage of water and having poor water/sewage drainage system were
      associated with self-rated mental health among the respondents.

PMID- 19742210
TI  - A qualitative study of the impact of HIV/AIDS on agricultural households in
      Southeastern Uganda.
AB  - The HIV/AIDS pandemic threatens economic, social, and environmental
      sustainability throughout sub-Saharan Africa. This paper reports on a qualitative
      study exploring interrelationships between HIV/AIDS, labor availability,
      agricultural productivity, household resources, food consumption, and health
      status in rural southeastern Uganda. Respondents reported an increase in widow
      and-orphan-headed households; labor shortages due to illness and caretaking;
      degradation of household resources from health-related expenses; loss of land
      tenure and assets following deaths, especially for widows and orphans; and
      changes in agricultural practices and productivity. Our study highlights a
      potential downward spiral of livelihood degradation for vulnerable households and
      suggests targeted interventions to improve sustainability.

PMID- 19742211
TI  - Renal replacement therapy in the intensive care unit.
AB  - Acute renal failure is a frequent complication in critically ill patients that
      carries with it considerable morbidity and mortality. The management of renal
      failure in patients with multi-organ failure is different from that of renal
      failure that presents as a single organ failure. Intermittent haemodialysis, done
      in the conventional manner may not be tolerated by most critically ill patients.
      Continuous renal replacement therapy is physiologically superior; however, there
      is lack of strong evidence to prove a clinical benefit. Hybrid therapies that
      combine the benefits of intermittent haemodialysis and continuous therapies have
      emerged in the past few years. These are simpler to carry out, provide more
      flexibility and may be cost effective and need to be studied in a systematic
      manner.

PMID- 19742212
TI  - Post-graduate CME.

PMID- 19742213
TI  - Relevance of ancient Indian wisdom to modern mental health - A few examples.
AB  - The ancient Indian concepts and paradigms relating to mental health are holistic
      and cover aspects that have been neglected by the modern mental health
      literature. The latter can borrow, study, and incorporate them in their text
      books to advantage. The current trend in mental health research is heavily biased
      in favour of biological aspects of psychological phenomena neglecting the basic
      entity, the mind. Correction of this partisan tilt is urgently needed.

PMID- 19742214
TI  - The doctor's dilemma: Truth telling.

PMID- 19742215
TI  - Psychosocial and cultural aspects of pseudocyesis.
AB  - Though considered rare in the developed countries, pseudocyesis is fairly common
      in gynecological practices in Africa. Using a case report and an overview of the
      literature, this paper posits that the elucidation of the psychosocial and
      cultural contexts within which a given patient lives can provide a basis for the
      empathic understanding of the reasons for the development of pseudocyesis. The
      case underscores the contributions of extreme poverty, relationship instability,
      and recurrent partner abuse in the enactment of pseudocyesis within a culture
      that treasures children for economic survival and generational continuity. The
      awareness of this cultural dimension is considered relevant to effective clinical
      care.

PMID- 19742216
TI  - Substance dependence: Decades apart in a teaching hospital.
AB  - AIM: The present study was done to understand the changing trends in substance
      dependence across decades. SETTINGS AND DESIGN: It is a retrospective study done
      in Department of Psychiatry in a Teaching Hospital setting. The data of patients
      who attended the OPD for substance dependence during the months January to
      December in the years 1985 & 1986, 1995 & 1996 and 2005 & 2006 were collected and
      analysed. MATERIALS AND METHODS: A total of 839 new patients with substance
      dependence identified according to International Classification of Diseases (ICD)
      (n = 839) was analysed in the present report. Study variables taken into account
      are alcohol dependence, polysubstance dependence which also includes alcohol,
      age, sex, age of initiation of substance use, duration of use, and comorbidity.
      STATISTICAL ANALYSIS: Z-test, Chi-square test, mean, percentages, standard
      deviation. RESULTS: Substance dependence constituted 5.32% in 1985 and 1986,
      5.02% in 1995 and 1996, and 4.05% in 2005 and 2006 of the newly registered total
      psychiatric patients. The variation in incidence figures across the years is
      statistically not significant (P > 0.05). Among the substance dependents 2% in
      1985 & 1986, 1% in 1995 & 1996 and 1% in 2005 & 2006 were females. Majority of
      the patients were alcohol dependent (87.2% in 1985 and 1986, 89.4% in 1995 and
      1996, and 79.6% in 2005 and 2006). Polysubstance dependence showed an increasing
      trend and it was statistically significant. Comparison of the years 1985 and 1986
      with 2005 and 2006 gives Z = 2.4, P < 0.05 (statistically significant).
      Comparison of the years 1995 and 1996 with 2005 and 2006 gives Z = 3, P < 0.01
      (significant statistically). Number of people getting initiated to substance use
      in early age (viz. 10-19 years) showed an increasing trend. People with positive
      family history of substance dependence started using substances early in life.
      (Chi-square value: 164.7, P < 0.0001, significant statistically). In
      polysubstance dependence comorbidity was more (Z = 4.1, P < 0.001, significant
      statistically). CONCLUSIONS: Incidence of substance dependence remained the same
      across the two decades. But incidence of polysubstance dependence is increasing
      over the years. People start using substances earlier and are becoming dependent
      earlier in their lives in the present decade. Polysubstance dependence is
      correlated with greater comorbidity. Early recognition of comorbidity and its
      management is essential for better prognosis. Substance dependence is exclusively
      a male diagnosis in our population.

PMID- 19742217
TI  - Understanding nutrition, depression and mental illnesses.

PMID- 19742218
TI  - Farmers' suicide in Vidarbha region of Maharashtra state: A myth or reality?
AB  - Incidence of farmers ending their lives in Vidarbha region had hit epidemic
      proportions recently. We adopted the psychological autopsy approach to offer some
      insight into the reason why these individuals resorted to such a drastic step.
      Suicide in farmers is public health problem and we suggested some immediate and
      serious interventions to prevent suicide.

PMID- 19742219
TI  - Central Institute of Psychiatry: A tradition in excellence.

PMID- 19742220
TI  - Inhalant abuse: A clinic-based study.
AB  - BACKGROUND: There are very few studies reporting inhalant abuse/dependence from
      India. MATERIALS AND METHODS: Consecutive treatment seeking inhalant abuse cases
      (n = 21) were studied for the sociodemographic and clinical profile by using a
      semi-structured interview schedule. RESULTS: A TYPICAL CASE PROFILE WAS:
      unmarried male (100%), mean age 19 years, government school background (76%),
      unemployed (43%) or student (38%), urban nuclear family (86%), middle
      socioeconomic status (76%), and poor social support (62%); inhalant dependence
      (81%), inhalants being the only substance of abuse (33%) and of first or second
      preference (76%). Duration of inhalant use ranged 6-60 (mean 16) months. All
      subjects abused typewriter erasing fluid by sniffing (67%), huffing (19%) or
      bagging (14%). Initiation was out of curiosity (62%), under peer pressure (24%),
      or as a substitute (14%). Craving was more common (90%) than withdrawal (57%).
      Almost half of the cases (48%) had a family history for substance dependence. All
      cases were impaired, more so in family and educational/occupational domains.
      CONCLUSIONS: The results depict that easy availability, cheap price, faster onset
      of action, and a regular high makes inhalant a substance of abuse especially
      among the urban youth.

PMID- 19742221
TI  - Poems by kumar.

PMID- 19742222
TI  - Biomedical markers and psychiatric morbidity of neurasthenia spectrum disorders
      in four outpatient clinics in India.
AB  - CONTEXT: Disorders of unexplained fatigue are researched globally and debated
      prominently concerning their biomedical and psychiatric comorbidity. Such studies
      are needed in India. AIMS: To identify biomedical markers and psychiatric
      morbidity of disorders of severe unexplained fatigue or weakness with disability,
      designated neurasthenia spectrum disorders (NSDs). To compare biomedical markers
      of patients with controls. To study correlation between biomedical markers and
      psychiatric morbidity. SETTINGS: Four specialty outpatient clinics of Psychiatry,
      Medicine, Dermatology, and Ayurved of an urban general hospital. DESIGN: Case
      control study for biomedical markers. Diagnostic interviews for assessment of
      psychiatric morbidity. MATERIALS AND METHODS: Patients (N = 352) were recruited
      using screening criteria and Structured Clinical Interview for DSM-IV screening
      module. They were compared with controls (N = 38) for relevant biomedical
      markers. Psychiatric morbidity was assessed with SCID-I interviews, Hamilton
      scales, and Symptom Check List-90 (SCL-90). Correlations between a nutritional
      index and axis I morbidity were studied. STATISTICAL ANALYSES: Frequencies and
      means of biomedical markers and psychiatric diagnoses were compared and
      associations assessed with regression analysis. RESULTS: Corrected arm muscle
      area (CAMA) was significantly lower among patients (P < 0.001), but not anemia.
      Anxiety (73.0%) and somatoform (61.4%) disorders, especially nonspecific
      diagnoses, were more frequent than depressive disorders (55.4%). Generally,
      Hamilton and SCL scores were lowest in Ayurved clinic, and highest in Psychiatry
      clinic. Presence of Generalized Anxiety Disorder (GAD) and adjustment disorders
      correlated with low nutritional index. CONCLUSIONS: Malnutrition or de
      conditioning that may explain weakness need to be considered in the management of
      NSDs in India, particularly with comorbid GAD or adjustment disorders. Weakness
      and anxiety, rather than fatigue and depression, are distinct features of Indian
      patients. SCL may be more useful than categorical diagnoses in NSDs. NSDs are an
      independent entity with nonspecific psychiatric comorbidity. Cross clinic
      differences among patients with similar complaints highlight need for idiographic
      studies.

PMID- 19742223
TI  - BIS-11A -Hindi version: A preliminary study of impulsivity in rural and urban
      Indian adolescents.
AB  - CONTEXT: Despite of there being a pressing need to gauge impulsivity scores,
      there is no behavioral instrument in India to assess the impulsivity in
      adolescents. No earlier studies have been done in India to access impulsivity in
      adolescents. Even in western countries, no study has been done in rural setting
      to access impulsivity, although segment of rural population is small in western
      nations with major population residing in urban areas. AIMS: To translate BIS-11A
      into Hindi from English in a culturally sensitive manner and to do preliminary
      study in rural and urban areas. SETTINGS AND DESIGN: First translation of BIS-11
      (as it is meant for adults) and cultural substitution resulted in Hindi adult
      version. Adolescent version was derived from adult version by replacing adult
      activities with adolescent activities. MATERIALS AND METHODS: BIS-11 English
      version was translated into Hindi and a back translation was made. As BIS-11 was
      developed for adults, answering some of the questions poses challenges for
      adolescents, so to be used with adolescents, questions that do not fit into
      adolescent age group were substituted keeping in view the activities of
      adolescents. Besides, questions that were not suitable as per the Indian culture
      were modified. Initially, these changes were made hypothetically by discussion
      among the authors and later a group of 48 school students were interviewed about
      the questions. Based on the interviews of students a final version was prepared.
      Translation, back translation, cultural substitution -hypothetically, and in
      school by discussion were carried out. The questionnaire was given to 120 urban
      high school students (in Jaipur, northern India) and 50 rural students (at
      Kanota, 25 km from Jaipur, northern India) and the scores were calculated as per
      the scoring method provided with original BIS-11. STATISTICAL ANALYSIS: T-test
      (two-tailed, two sample unequal variance, i.e., type 3) was used. RESULTS: T-test
      (two-tailed, two sample unequal variance, i.e., type 3) found no significant
      difference between impulsivity scores of adolescents of urban and rural areas t
      0.05(2)1 = 0.57, |t| < t 0.05(2)1, P > 0.05, P = 12.706. There were no gender
      related differences either. CONCLUSIONS: As impulsivity can lead to suicide and
      is implicated for substance abuse in disorders like Schizophrenia, it is
      important that culturally sensitive impulsivity studies are done in India on a
      large scale keeping in view the large size of population. Standardization of the
      BIS11-A Hindi version is being taken up. The work on Hindi version also generates
      necessity for other tasks if BIS-11(Hindi version) is to be used widely. Work on
      psychometric properties of Hindi version of BIS-11 A is being taken up. There is
      a need to devise a quick way to calculate impulsivity scores keeping in view the
      large population of India (1 billion out of which at least 33% is Hindi speaking,
      Census Survey of India, 2001). Besides, BIS-11A needs to be developed for other
      regional languages in India as there is a high-linguistic diversity in India.

PMID- 19742225
TI  - Poem by asha.

PMID- 19742224
TI  - Valproate monotherapy induced-delirium due to hyperammonemia: A report of three
      adult cases with different types of presentation.
AB  - One of the important adverse effects of valproate is delirium due to
      hyperammonemia. In this case report series, we are reporting three cases with
      interesting and different types of clinical presentation on valproate
      monotherapy. Valproate-induced delirium may be mistaken for psychosis or
      worsening of mania leading to improper diagnosis and poor management. We found
      that there was an elevated level of plasma ammonia in our cases during the
      delirious state and which decreased when valproate was discontinued. In our cases
      the serum valproate levels, liver function tests, electroencephalogram, and
      imaging studies were normal, which were deranged in the previous case reports. We
      are the first to rechallenge valproate in one of the cases, to prove that
      valproate caused the hyperammonemia. We suggest that plasma ammonia levels should
      be monitored routinely in all cases of altered mental status and receiving
      valproate therapy.

PMID- 19742226
TI  - Child in India.

PMID- 19742227
TI  - Early intervention in schizophrenia.
AB  - Early intervention (EI) programs in schizophrenia and other psychoses are aimed
      at early detection (ED) of the disease; prevent conversion to manifested
      psychosis and phase-specific treatment to reduce development of chronic
      disabilities. EI strategies include targeting people at "high risk" for
      developing schizophrenia, intervening in prodromal phase of schizophrenia, and
      reducing the "duration of untreated psychosis" (DUP). Services are delivered by a
      specialized team and are usually resource intensive. Several strategies like
      treatment with antipsychotics, family interventions, and cognitive behavior
      therapy have been tried with modest success in prodromal patients. Significant
      ethical reservations exist regarding exposing prodromal patients to the stigma of
      labeling as "high risk for schizophrenia" and side effects of psychotropics in
      the absence of clear evidence of efficacy in favor of ED, intervention by
      specialist teams, and phase-specific interventions in prodrome of psychosis. More
      research is warranted to demonstrate the risk-benefit and cost-benefit of such
      interventions before these can be routinely recommended.

PMID- 19742229
TI  - The national institute of open schooling.

PMID- 19742228
TI  - Perceptions of drug use within a UK Bengali community.
AB  - AIM: The study set out to explore the perceptions and knowledge of drug use of
      the Bangladeshi origin population in Leicester through local Mosques and
      community and resource centers for recruiting subjects. SETTING AND DESIGN: A
      triangulated methodology was used for this research. A review of all available
      literature was carried out to establish if there was evidence of a drug problem
      among the Bangladeshis in the UK along with questionnaires and interviews.
      MATERIALS AND METHODS: A triangulated methodology was used for this research. A
      review of all available literature was carried out along with questionnaires as
      well as semi-structured interviews using self-designed questionnaires. RESULTS
      AND CONCLUSIONS: Only 66 questionnaires (16.5%) were returned (46 males and 20
      females). These and qualitative exploratory interviews with a small number of
      community leaders confirmed that drug-related problems exist among the
      Bangladeshi community, especially in the younger age group and are recognized as
      such but help seeking is often problematic. An understanding of the perceptions
      of the Bangladeshi population is useful in developing culturally appropriate
      services for this group.

PMID- 19742230
TI  - Difficult to manage the concerns of parents of a scizophrenic patient related to
      side effects of clozapine.

PMID- 19742231
TI  - Flashbacks in social anxiety disorder: Psychopathology of a case.
AB  - Social anxiety disorder is characterized by overwhelming anxiety in everyday
      situations which are frequently avoided due to a fear of being watched and
      scrutinized by others or acting in an embarrassing way. Flashbacks are typical
      symptoms of post-traumatic stress disorder, and their main features are intrusive
      and vivid images that occur in a waking state. We present a case study of a man
      diagnosed with social anxiety disorder who had reexperiencing symptoms similar to
      flashbacks of what he considered "shameful situations". The differential aspects
      between flashbacks and obsessional imagery are discussed. Reexperiencing symptoms
      and imagery of social phobia as well as the sociocultural influence over the
      symptomatology of psychiatric disorders are then highlighted.

PMID- 19742232
TI  - Internet addiction disorder: Fact or Fad? Nosing into Nosology.

PMID- 19742233
TI  - Neuropsychology of prefrontal cortex.
AB  - The history of clinical frontal lobe study is long and rich which provides
      valuable insights into neuropsychologic determinants of functions of prefrontal
      cortex (PFC). PFC is often classified as multimodal association cortex as
      extremely processed information from various sensory modalities is integrated
      here in a precise fashion to form the physiologic constructs of memory,
      perception, and diverse cognitive processes. Human neuropsychologic studies also
      support the notion of different functional operations within the PFC. The
      specification of the component 'executive' processes and their localization to
      particular regions of PFC have been implicated in a wide variety of psychiatric
      disorders.

PMID- 19742234
TI  - Temperamental traits of breath holding children: A case control study.
AB  - BACKGROUND: Clinical observation and few anecdotal reports suggest that the
      children with breath holding spells (BHS) have certain temperamental traits,
      which predispose them to behave in certain way. They seem to have low frustration
      tolerance, which leads to adamant behavior. Vigorous crying, through various
      mechanisms, precipitates BHS. MATERIALS AND METHODS: We assessed the
      temperamental traits of 30 children with BHS and compared them with 30 normal
      children after matching for age, sex, and socioeconomic status. Temperament was
      measured using 'Temperament measurement Schedule'. RESULTS: The data were
      analyzed using Mann-Whitney U test. The following temperamental traits, threshold
      of responsiveness (P<0.001), mood (P<0.001), activity level (P<0.001), intensity
      of emotions (P<0.001), distractibility (P<0.001) and rhythmicity (P<0.05) were
      found to be significantly different from the control group. Two factors, namely
      sociability (P<0.05) and energy level (P<0.001) were significantly higher in
      breath holders. CONCLUSIONS: Significantly differing temperamental traits in
      breath holders suggests that these could influence the behavioral pattern
      exhibited by them. Breath holding spells can act as an easy marker for difficult
      temperamental traits, which gives an early opportunity to shape their difficult
      behavior.

PMID- 19742235
TI  - Schizophrenia: Impact on quality of life.
AB  - AIMS: The purpose of the present study was to assess quality of life (QOL) in
      patients with schizophrenia and to determine influence of clinical factors and
      socio-demographic variables on QOL of schizophrenic patients. SETTING AND DESIGN:
      Cross-sectional study carried out on outdoor patients attending Department of
      Psychiatry, SMS Medical College, Jaipur, India. MATERIALS AND METHODS: Fifty
      patients of schizophrenia diagnosed as per ICD - 10 with minimum duration of
      illness being two years and attending out patient department (OPD) at psychiatric
      centre or psychiatric clinic at SMS medical college, hospital, Jaipur, India for
      maintenance treatment fulfilling the criteria given below were registered. They
      were evaluated using positive and negative syndrome scale (PANSS) and Quality of
      Life Instrument (WHO QOL - BREF). The data collected on above tools, was analyzed
      using descriptive and inferential statistics using Pearson correlation
      coefficient. RESULTS AND CONCLUSIONS: Patients were having lowest QOL scores in
      social relationships domain of WHO QOL - BREF scale. Social relationship domain
      of QOL was significantly negatively correlated with occupation with employed
      patients reporting better QOL in this domain. There were significant positive
      correlation of total monthly income with social relationship domain and total
      QOL. There were no statistically significant correlation between QOL parameters
      and clinical characteristics in schizophrenics. Scores on positive subscale and
      total PANSS were significantly negatively correlated with physical,
      Psychological, social relationship domains and total QOL. Negative subscale had
      significant negative correlation with physical and psychological domains and
      total QOL. General psychopathology subscale had significant negative correlation
      with all subscales of QOL. This study confirms poor QOL in schizophrenia despite
      significant improvement with pharmacological treatment.

PMID- 19742236
TI  - Roadmap for sexual medicine: Agenda for Indian Psychiatric Society.

PMID- 19742237
TI  - A study in dualism: The strange case of Dr. Jekyll and Mr. Hyde.
AB  - R. L. Stevenson's novel, The Strange Case of Dr. Jekyll and Mr. Hyde is a
      prominent example of Victorian fiction. The names Jekyll and Hyde have become
      synonymous with multiple personality disorder. This article seeks to examine the
      novel from the view point of dualism as a system of philosophy and as a religious
      framework and also from the view point of Freud's structural theory of the mind.

PMID- 19742238
TI  - Rapid urbanization - Its impact on mental health: A South Asian perspective.
AB  - Rapid increase in urban population as a proportion of total population is
      resulting in rapid urbanization of the world. By the end of 2008, a majority of
      the world's population will be living in the cities. This paradigm shift in the
      dynamics of human population is attracting attention of demographers,
      sociologists, scientists, and politicians alike. Urbanization brings with it a
      unique set of advantages and disadvantages. Though it is driving the economies of
      most of the nations of the world, a serious concern regarding the impact of
      urbanization on mental health is warranted. The impact of urbanization on mental
      health in South-Asian countries needs to be examined. These countries by virtue
      of their developing economies and a significant proportion of population still
      living below poverty line are particularly vulnerable and tend to have a higher
      burden of diseases with an already compromised primary health care delivery
      system. The range of disorders and deviancies associated with urbanization is
      enormous and includes psychoses, depression, sociopathy, substance abuse,
      alcoholism, crime, delinquency, vandalism, family disintegration, and alienation.
      Thus, it is a heterogenous mix of problems and categorizing them to one
      particular subtype seems daunting and undesirable. Urbanization is affecting the
      entire gamut of population especially the vulnerable sections of society -
      elderly, children and adolescents, and women. Rapid urbanization has also led to
      creation of "fringe population" mostly living from hand to mouth which further
      adds to poverty. Poverty and mental health have a complex and multidimensional
      relationship. Urban population is heavily influenced by changing cultural
      dynamics leading to particular psychiatric problems like depression, alcoholism,
      and delinquency. Judicious use of resources, balanced approach to development,
      and sound government policies are advocated for appropriate growth of advancing
      economies of South-Asian region.

PMID- 19742239
TI  - Some professional experiences.
AB  - THIS NARRATIVE OF SOME OF MY PROFESSIONAL EXPERIENCES ATTEMPTS TO PRESENT
      CIRCUMSTANCES IN WHICH I ARRIVED AT CERTAIN CONCLUSIONS LIKE: (a) Subjective
      personal experiences can be valid contributors to integration of a professional's
      world-view. (b) Concepts and constructs relating to diagnosis and other systems
      of understanding and practice are useful only as reference-systems. Rigidity in
      their use can be counter-productive. (c) Mental health profession is not always
      indispensable to patient's well being. Professional pride is an obstacle to
      learning. (d) Psychotherapy is not consciously done, but is a natural consequence
      of therapist's efforts to understand the patient and his/her predicament.
      Therapist's qualities play a predominant role. (e) Usefulness of therapeutic
      methods and techniques is dependent entirely on how the therapist uses them. (f)
      Absolute therapeutic effectiveness is a myth. (g) Indian mythology can offer a
      system of "Psycho-pathology," a system of explanation and management, parallel to
      existing systems.

PMID- 19742240
TI  - Critical evaluation of current diagnostic systems.

PMID- 19742241
TI  - Endoscopic thoracic laminoforaminoplasty for the treatment of thoracic
      radiculopathy: report of 12 cases.
AB  - BACKGROUND: Spinal stenosis of the thoracic spine is less common than that of the
      cervical and lumbar regions. Due to the close proximity to thoracic and abdominal
      organs, surgical operations can be difficult and carry a greater risk of
      complications. The most efficacious intervention for thoracic stenosis, whether
      central or foraminal, refractory to conservative management is uncertain. We
      aimed to evaluate the efficacy of endoscopic laminoforaminoplasty (ELFP) in the
      treatment of thoracic radiculopathy. METHODS: Twelve patients with radicular pain
      involving the lower thoracic levels (at or below T6) were treated with ELFP.
      RESULTS: Seven of twelve patients showed marked improvement in pain scores.
      Average follow-up scores were 2.9 and 12.08 on the Visual Analog Scale (VAS) and
      Oswestry Disability Index, respectively. The significance was 0.005 between the
      pre and post surgical data. One patient with moderate symptoms, two with severe
      symptoms, and two with crippling symptoms did not report significant improvement
      on VAS or Oswestry. No complications were encountered. CONCLUSIONS: Endoscopic
      laminoforaminoplasty offers an alternative to fusion or conventional laminotomy
      with similar success rates. Patients additionally benefit from a decrease risk of
      complications, short hospital stay, and faster recovery.

PMID- 19742242
TI  - Protective effects of garlic and silymarin on NDEA-induced rats hepatotoxicity.
AB  - BACKGROUND: The present study was conducted to investigate the chemopreventive
      effects of garlic extract and silymarin on N-nitrosodiethylamine (NDEA) and
      carbon tetrachloride (CCl(4))-induced hepatotoxicity in male albino rats. METHODS
      AND RESULTS: Animals were pretreated with garlic, silymarin or both for one week
      prior to the injection of NDEA. Then animals received a single injection of NDEA
      followed by weekly subcutaneous injections of CCl(4) for 6 weeks. Oral
      administration was then continued along with the injection of CCl(4) for the
      duration of the experiment. Serum aspartate transaminase (AST), alanine
      transaminase (ALT), alkaline phosphatase (ALP), hepatic lipid peroxidation (LPO),
      superoxide dismutase (SOD), reduced glutathione (GSH), glutathione-S-transferase
      (GST) and glutathione reductase (GSR) were measured. Injection of NDEA induced a
      significant elevation in serum AST, ALT and ALP. In the liver, NDEA increased
      oxidative stress through the increase in LPO and decrease in SOD, and GSH
      dependent enzymes. Although administration of garlic or silymarin significantly
      reduced the liver toxicity, combined administration was more effective in
      preventing the development of hepatotoxicity. CONCLUSION: These novel findings
      suggest that silymarin and garlic have a synergistic effect, and could be used as
      hepatoprotective agents against hepatotoxicity.

PMID- 19742243
TI  - Disruption of the BMEI0066 gene attenuates the virulence of Brucella melitensis
      and decreases its stress tolerance.
AB  - Brucella melitensis is a facultative intracellular pathogen. An operon composed
      of BMEI0066, which encodes a two-component response regulator CenR, and BMEI0067,
      which encodes a cAMP-dependent protein kinase regulatory subunit, has been
      predicted to exist in many bacterial species. However, little is known about the
      function of this operon. In order to characterize this operon and assess its role
      in virulence, we constructed a marked deletion mutant of BMEI0066. The mutant was
      less able to withstand hyperosmotic conditions than wild-type (16M), but showed
      no significant difference with 16M when challenged by H(2)O(2). The mutant also
      showed increased sensitivity to elevated temperature (42 degrees C) and a reduced
      survival ratio under acidic conditions compared with 16M. The mutant failed to
      replicate in cultured murine macrophages and was rapidly cleared from the spleens
      of experimentally infected BALB/c mice. These findings suggest that these operon
      products make an important contribution to pathogenesis in mice, probably by
      allowing B. melitensis to adapt to the harsh environment encountered within host
      macrophages.

PMID- 19742244
TI  - Rapid response systems.
AB  - Intensive care medicine was for many years practiced within the four walls of an
      intensive care unit (ICU). Evidence then emerged that many serious adverse events
      in hospitals were preceded by many hours of slow deterioration, resulting in
      multi-organ failure and potentially preventable admissions to the ICU.
      Ironically, these admissions may have been prevented if the skills within the ICU
      had been available to the patient on the general ward at an earlier stage. The
      concept of a Medical Emergency Team (MET) was developed to enable staff from the
      ICU to rapidly identify and respond to serious illness at an earlier stage and,
      hopefully, prevent serious complications. Since then, other forms of rapid
      response and outreach systems have been developed. Increasingly, physicians
      working in ICUs can see the benefit of the early management of serious illness in
      order to improve patient outcome.

PMID- 19742245
TI  - Quality and performance improvement in critical care.
AB  - In the past decade, there is an increased focus on quality and safety in health
      care. Decreasing variation, increasing adherence to evidence based guidelines,
      monitoring processes, and measuring outcomes are critical for improving quality
      of care. Intensivists have broad knowledge of hospital organization, and need to
      be leaders in quality improvement efforts.

PMID- 19742246
TI  - A process for instituting best practice in the intensive care unit.
AB  - Goals of health care are patient safety and quality patient outcomes. Evidence
      based practice (EBP) is viewed as a tool to achieve these goals. Health care
      providers strive to base practice on evidence, but the literature identifies
      numerous challenges to implementing and sustaining EBP in nursing. An initial
      focus is developing an organizational culture that supports the process for
      nursing and EBP. An innovative strategy to promote a culture of EBP was
      implemented in a tertiary center with 152 critical care beds and numerous
      specialty units with diverse patient populations. A multi-disciplinary committee
      was developed with the goal to use evidence to improve the care in the critical
      care population. EBP projects were identified from a literature review. This
      innovative approach resulted in improved patient outcomes and also provided a
      method to educate staff on EBP. The committee members have become advocates for
      EBP and serve as innovators for change to incorporate evidence into decision
      making for patient care on their units.

PMID- 19742247
TI  - Patient safety: Needs and initiatives.
AB  - Patient safety has become a major defining issue for healthcare at the beginning
      of the 21(st) century. Viewed from the perspective of reliability of delivery of
      best practice, healthcare systems demonstrate a degree of imperfection which
      would not be tolerated in industry. In part, this is because of uncertainty about
      what constitutes best practice, combined with complex interventions in complex
      systems. The acutely ill patient is particularly challenging, and as the majority
      of admissions to hospitals are emergencies, it makes sense to focus on this group
      as a coherent entity. Changing clinical behavior is central to improving safety,
      and this requires a systems-wide approach integrating care throughout patient
      journey, combined with incorporating reliability training in life-long learning.

PMID- 19742248
TI  - Cost of intensive care in India.
AB  - Critical care is often described as expensive care. However, standardized
      methodology that would enable determination and international comparisons of cost
      is currently lacking. This article attempts to review this important issue and
      develop a framework through which cost of critical care in India could be
      analyzed.

PMID- 19742249
TI  - Obstructive sleep apnoea and anaesthesia.
AB  - Obstructive sleep apnoea (OSA) correlates positively with obesity and age, both
      of which are becoming increasingly prevalent. Obstructive sleep apnoea occurs
      much more frequently in clinical practice than formerly diagnosed, and that this
      condition represents complex challenges for difficulty in mask ventilation,
      laryngoscopic intubation, accelerated arterial desaturation, postoperative
      monitoring and discharge status. In this review article pathophysiology,
      diagnosis, and perioperative management of this group of patients have been
      discussed in detail.

PMID- 19742250
TI  - Successful management of massive intraoperative pulmonary fat embolism with
      percutaneous cardiopulmonary support.
AB  - We report a patient who sustained catastrophic pulmonary fat embolism, during
      open reduction, internal fixation (ORIF) of fracture femur. In our opinion, the
      use of percutaneous cardiopulmonary support with (PCPS), saved the patient from
      certain death.

PMID- 19742251
TI  - Artificial blood.
AB  - Artificial blood is a product made to act as a substitute for red blood cells.
      While true blood serves many different functions, artificial blood is designed
      for the sole purpose of transporting oxygen and carbon dioxide throughout the
      body. Depending on the type of artificial blood, it can be produced in different
      ways using synthetic production, chemical isolation, or recombinant biochemical
      technology. Development of the first blood substitutes dates back to the early
      1600s, and the search for the ideal blood substitute continues. Various
      manufacturers have products in clinical trials; however, no truly safe and
      effective artificial blood product is currently marketed. It is anticipated that
      when an artificial blood product is available, it will have annual sales of over
      $7.6 billion in the United States alone.

PMID- 19742252
TI  - Thrombotic thrombocytopenic purpura and systemic lupus erythematosus: successful
      management of a rare presentation.
AB  - Thrombotic thrombocytopenic purpura (TTP) and systemic lupus erythematosus (SLE)
      very rarely present simultaneously and pose a diagnostic and therapeutic dilemma
      to the critical care team. Prompt diagnosis and management with plasma exchange
      and immunosuppression is life-saving. A patient critically ill with TTP and SLE,
      successfully managed in the acute period of illness with plasma exchange,
      steroids and mycophenolate mofetil is described.

PMID- 19742253
TI  - Physician beliefs and practice regarding end-of-life care in India.
AB  - BACKGROUND AND AIMS: Physician beliefs and practices largely determine the
      withdrawal of life support in intensive care units. No information exists
      regarding beliefs regarding the withdrawal of life support among physicians in
      India. MATERIALS AND METHODS: We performed a questionnaire at the NAPCON
      conference in Jaipur. RESULTS: One hundred and twenty-two questionnaires were
      completed and returned. The majority of respondents did not apply do not
      resuscitate orders. Most physicians stated withdrawal of life support was not
      allowed or practiced at their institution. Thirty-five percent of physicians
      stated they performed life-support withdrawal. Barriers to good end-of-life care
      were primarily legal but also included hospital policy and social constraints.
      CONCLUSIONS: Pulmonary and critical care physicians in India have a lower rate of
      withdrawal of life support than western physicians. The reasons seem to be
      primarily legal and policy related. Culture and religion were not identified as
      barriers. Clarification of the legal and policy status of withdrawal of life
      support is needed.

PMID- 19742254
TI  - Prediction of arterial blood gas values from arterialized earlobe blood gas
      values in patients treated with mechanical ventilation.
AB  - BACKGROUND/OBJECTIVE: Arterial blood gas (ABG) analysis is useful in evaluation
      of the clinical condition of critically ill patients; however, arterial puncture
      or insertion of an arterial catheter may sometimes be difficult and cause many
      complications. Arterialized ear lobe blood samples have been described as
      adequate to gauge gas exchange in acute and chronically ill pediatric patients.
      PURPOSE: This study evaluates whether pH, partial pressure of oxygen (PO(2)),
      partial pressure of carbon dioxide (PCO(2)), base excess (BE), and bicarbonate
      (HCO(3)) values of arterialized earlobe blood samples could accurately predict
      their arterial blood gas analogs for adult patients treated by mechanical
      ventilation in an intensive care unit (ICU). SETTING: A prospective descriptive
      study. METHODS: Sixty-seven patients who were admitted to ICU and treated with
      mechanical ventilation were included in this study. Blood samples were drawn
      simultaneously from the radial artery and arterialized earlobe of each patient.
      RESULTS: Regression equations and mean percentage-difference equations were
      derived to predict arterial pH, PCO(2), PO(2), BE, and HCO(3)-values from their
      earlobe analogs. pH, PCO(2), BE, and HCO(3) all significantly correlated in ABG
      and earlobe values. In spite of a highly significant correlation, the limits of
      agreement between the two methods were wide for PO(2). Regression equations for
      prediction of pH, PCO(2), BE, and HCO3- values were: arterial pH (pHa) = 1.81+
      0.76 x earlobe pH (pHe) [r = 0.791, P < 0.001]; PaCO(2) = 1.224+ 1.058 x
      earlobePCO(2) (PeCO(2)) [r = 0.956, P < 0.001]; arterial BE (BEa) = 1.14+ 0.95 x
      earlobe BE (BEe) [r= 0.894, P < 0.001], and arterial HCO(3)- (HCO(3)-a) = 1.41+
      earlobe HCO(3)(HCO(3)-e) [r = 0.874, P < 0.001]. The predicted ABG values from
      the mean percentage-difference equations were derived as follows: pHa = pHe x
      1.001; PaCO(2) = PeCO(2) x 0.33; BEa = BEe x 0.57; and HCO(3)-a = HCO(3)-e x
      1.06. CONCLUSIONS: Arterialized earlobe blood gas can accurately predict the ABG
      values of pH, PCO(2), BE, and HCO(3)- for patients who do not require regular
      continuous blood pressure measurements and close monitoring of arterial PO(2)
      measurements.

PMID- 19742255
TI  - Incidence and management of diaphragmatic palsy in patients after cardiac
      surgery.
AB  - BACKGROUND: Diaphragm is the most important part of the respiratory system.
      Diaphragmatic palsy following cardiac surgery is not uncommon and can cause
      deterioration of pulmonary functions and attendant pulmonary complications.
      OBJECTIVES: Aim of this study was to observe the incidence of diaphragmatic palsy
      after off pump coronary artery bypass grafting (OPCAB) as compared to
      conventional CABG and to assess the efficacy of chest physiotherapy on
      diaphragmatic palsy in post cardiac surgical patients. DESIGN AND SETTING: An
      observational prospective interventional study done at a tertiary care cardiac
      centre. PATIENTS: 2280 consecutive adult patients who underwent cardiac surgery
      from February 2005 to august 2005. RESULTS: 30 patients out of 2280 (1.31%)
      developed diaphragmatic palsy. Patients were divided based on the presence or
      absence of symptoms viz. breathlessness at rest or exertion or with the change of
      posture along with hypoxemia and / or hypercapnia. Group I included 14 patients
      who were symptomatic (CABG n=13, post valve surgery n=1), While Group II included
      16 asymptomatic patients (CABG n=12, post valve surgery n=4), 9 patients (64%)
      from Group I (n=14) and 4 patients (25%) from group II showed complete recovery
      from diaphragmatic palsy as demonstrated ultrasonographically. CONCLUSION: The
      incidence of diaphragmatic palsy was remarkably less in our adult cardiac
      surgical patients because most of the cardiac surgeries were performed off pump
      and intensive chest physiotherapy beginning shortly after extubation helped in
      complete or near complete recovery of diaphragmatic palsy. Chest Physiotherapy
      led to marked improvement in functional outcome following post cardiac surgery
      diaphragmatic palsy. We also conclude that ultrasonography is a simple valuable
      bed-side tool for rapid diagnosis of diaphragmatic palsy.

PMID- 19742256
TI  - Refeeding syndrome.
AB  - We report a case of a fifty-year-old male who was admitted with a three month
      history of increasing weakness, prostration, decreasing appetite and inability to
      swallow. The patient was a chronic alcoholic, unemployed, and of very poor
      socioeconomic background. The patient was initially investigated for upper GI
      malignancy, Addisons disease, bulbar palsy and other endocrinopathies. Concurrent
      management was started for severe electrolyte abnormalities and enteral
      nutritional supplementation was begun. By the fourth day of feeding patient
      developed severe hypophosphatemia and other life-threatening features suggesting
      refeeding syndrome. The patient was managed for the manifestations of refeeding
      syndrome. A final diagnosis of chronic alcoholic malnutrition with refeeding
      syndrome was made. Refeeding of previously starving patients may lead to a
      variety of complications including sudden death.

PMID- 19742257
TI  - Platelet counts and outcome in the pediatric intensive care unit.
AB  - OBJECTIVES: Thrombocytopenia is commonly observed in critically ill patients.
      This study was undertaken to evaluate the variation in platelet counts and the
      risk factors associated with thrombocytopenia and mortality in pediatric
      intensive care patients. In addition, prognostic value of platelet counts for
      outcome in pediatric intensive care unit was studied. STUDY DESIGN: Prospective,
      observational cohort analysis. SETTING: 8- bedded pediatric intensive care unit
      of a tertiary care teaching hospital. PATIENTS: All consecutively admitted
      patients (n=138) staying in the pediatric intensive care unit (PICU) for at least
      48h over a 7 months period were studied. MEASUREMENTS AND MAIN RESULTS:
      Thrombocytopenia was defined as platelet counts <150.0/nL. Median 1(st) day
      Pediatric Risk of Mortality Score (PRISM) was 5 (range 0-30) and median ICU stay
      was 4 days (range 2-98 days). Twenty five percent patients had at least one
      episode of thrombocytopenia during the stay. Twenty percent of these patients had
      thrombocytopenia on admission and rest (80%) developed it during the PICU stay.
      Seventy one percent (19) of the patients developed thrombocytopenia by fourth day
      of admission. Patients with PICU acquired thrombocytopenia had statistically
      significant lower baseline, nadir and 4th day platelet counts and a significantly
      higher drop in platelet counts (56% vs. 6% P<0.001) as compared to non
      thrombocytopenic patients. PRISM score, long PICU stay, sepsis, coagulopathy, and
      creatinine levels were significantly associated with occurrence of
      thrombocytopenia. Patients with thrombocytopenia had higher probability of
      bleeding (34% vs. 15%, P=0.01). Higher platelet counts on admission were
      associated with significantly reduced risk of thrombocytopenia (P=0.00) Baseline,
      nadir and day-4 platelet counts, presence of thrombocytopenia on admission,
      sepsis, coagulopathy and a higher mean PRISM score on univariate analysis were
      significantly associated with mortality. Leucopenia or leucocytosis,
      thrombocytopenia and coagulopathy were found to significantly affect outcome.
      Drop in platelet counts was found to have slightly higher discriminative value
      for mortality prediction than PRISM on the ROC curve. The survivors had higher
      platelet counts throughout the PICU stay and after an initial fall in platelet
      counts in the PICU showed a significantly higher rise in the platelet counts in
      the following days than the non-survivors. CONCLUSIONS: Thrombocytopenia is
      common in PICU. Patients requiring cardiopulmonary resuscitation or with
      circulatory shock, coagulopathy, sepsis and with more severe disease have higher
      risk of developing thrombocytopenia. Thrombocytopenic patients have a higher risk
      of bleeding. Drop in platelet counts >27% and thrombocytopenia were independently
      related to mortality. Serial measurements of platelet counts are better
      predictors of pediatric intensive care outcome than one-time values. Any drop in
      platelet counts even without thrombocytopenia needs an urgent and extensive
      evaluation.

PMID- 19742258
TI  - Arterialised blood gas sampling in the critically ill: correct tools for the job?

PMID- 19742259
TI  - Transfusion associated graft versus host disease in an immunocompetent individual
      following coronary artery bypass grafting.
AB  - Transfusion associated graft versus host disease (TA-GVHD) is a rare but commonly
      fatal complication of transfusion of cellular blood products, which usually
      occurs in immunosuppressed individuals following transfusion and subsequent
      engraftment of viable T lymphocytes. Very rarely it may arise in apparently
      immunocompetent individuals. The clinical syndrome consists of fever, skin rash,
      diarrhoea, hepatic dysfunction, and bone marrow aplasia. The outcome is nearly
      always fatal. We present here a case report of fatal TA-GVHD in a "presumed"
      immunocompetent patient, post coronary artery bypass grafting surgery after
      transfusion of blood products. The patient died 24 days after transfusion. There
      is a perceived increased risk of TA-GVHD following bypass grafting and other
      surgical procedures where cardiopulmonary bypass is required. TA-GVHD is probably
      underreported and the incidence is felt to be too low to warrant routine
      irradiation of cellular products for this group of patients. Clinicians,
      pathologists, and transfusion centers should be aware of this rare but
      devastating complication of blood transfusion after cardiac surgery.

PMID- 19742260
TI  - Effects of mobile phone use on specific intensive care unit devices.
AB  - BACKGROUND AND AIMS: To observe the effects of mobile phone use in the vicinity
      of medical devices used in a critical care setting. SUBJECTS AND METHODS:
      Electromagnetic interference (EMI) was tested by using two types of mobile phones
      - GSM and CDMA. Mobile phones were placed at a distance of one foot from three
      medical devices - syringe pump, mechanical ventilator, and the bedside monitor -
      in switch off, standby, and talking modes of the phone. Medical devices were
      observed for any interference caused by the electromagnetic radiations (EMR) from
      the mobile phones. RESULTS: Out of the three medical devices that were tested,
      EMI occurred while using the mobile phone in the vicinity of the syringe pump, in
      the 'talk mode.' The mean variation observed in the calculated and delivered
      volume of the syringe pump was 2.66 ml. Mechanical ventilator did not show any
      specific adverse effects with mobile phone use in the one-foot vicinity. No other
      adverse effects or unexplained malfunctions or shutdown of the syringe pump,
      mechanical ventilator, or the bedside monitor was noted during the study period
      of 36 hours. CONCLUSION: EMI from mobile phones have an adverse effect on the
      medical devices used in critical care setup. They should be used at least one
      foot away from the diameter of the syringe pump.

PMID- 19742261
TI  - Noninvasive ventilation: a survey of practice patterns of its use in India.
AB  - BACKGROUND AND AIMS: To understand the practice patterns of noninvasive
      ventilation (NIV) use by Indian physicians. SUBJECTS AND METHODS: Around three
      thousand physicians from all over India were mailed a questionnaire that could
      capture the practice patterns of NIV use. RESULTS: Completed responses were
      received from 648 physicians (21.6%). Majority (n = 469, 72.4%, age 40 +/- 9
      years, M:F 409:60) use NIV in their clinical practice. NIV was most exclusively
      being used in the ICU setting (68.4%) and the commonest indication for its use
      was chronic obstructive pulmonary disease (COPD) (71.4%). A significant number
      did not report use of a conventional ventilator for NIV support (62%). Oronasal
      mask was the overwhelming favorite among the sampled physicians (68.2%). In most
      of the cases, the treating physician initiated NIV (60.8%) and a baseline blood
      gas analysis was performed in only 71.1% of the cases (315/443). Nasal bridge
      pressure sores was the commonest complication (64.2%). CONCLUSIONS: NIV is being
      widely used in clinical practice in India for various indications. COPD is the
      most common indication for its deployment. There seems to be a marked variability
      in the patterns relating to actual deployment of NIV, including the site of
      initiation, protocols for initiation followed, and monitoring of patients.

PMID- 19742262
TI  - Indoxacarb poisoning: an unusual presentation as methemoglobinemia.
AB  - We describe the management of a case of methemoglobinemia secondary to ingestion
      of indoxacarb, an oxadiazine insecticide.

PMID- 19742263
TI  - Calcium channel blocker overdose: experience with amlodipine.
AB  - Amlodipine overdose is only scarcely reported from India. We report two cases of
      near fatal Amlodipine overdose managed in our ICU with fluid, vasopressors,
      calcium infusion and Glucagon. Literature is reviewed and other treatment
      modalities discussed.

PMID- 19742264
TI  - Impact of preoperative mild renal dysfunction on short term outcome in isolated
      Coronary Artery Bypass (CABG) patients.
AB  - BACKGROUND AND AIM: It is well known that dialysis dependent renal failure
      increases the likelihood of poor outcome following cardiac surgery. But the
      results of CABG in patients with mild renal dysfunction are not clearly
      established. The aim of the study is to analyze the risk of preoperative mild
      renal dysfunction on outcome after isolated coronary surgery. MATERIALS AND
      METHODS: We reviewed prospectively collected data between June 2006-Nov 2006 in
      488 patients who underwent isolated CABG. We separated the data into two groups.
      Control group having normal renal function and study group having mild renal
      dysfunction (serum creatinine 1.4 mg-2.2 mg%). Among 488 patients, 412 patients
      were in control group and 76 patients were in the study group. RESULTS: Analysis
      of data showed significant postoperative complications in the mild renal
      dysfunction group, like increased operative mortality (7.5% vs 1.6%), increased
      requirement of postoperative renal replacement therapy (10% vs 1.2%), increased
      incidence of new onset atrial fibrillation (20% vs 4.2%) and prolonged duration
      of ICU stay. Multivariate analysis adjusting for known risk factors confirmed
      preoperative mild renal dysfunction (S.creat.1.4-2.2 mg/dl) is an independent
      risk factor for postoperative morbidity and mortality. (Adj. OR: 4.47; 95% CI:
      1.41-14.16; P=0.010). CONCLUSION: Mild renal dysfunction is an important
      independent predictor of outcome in terms of in-hospital mortality and morbidity
      in patients undergoing CABG.

PMID- 19742265
TI  - A rare malposition of the thoracic venous catheter introduced via the left
      internal jugular vein.
AB  - A rare malposition of central venous catheter in the left superior intercostal
      vein is described. The diagnostic features and the possible ways to prevent this
      complication are discussed.

PMID- 19742266
TI  - Post intubation tracheal stenosis.
AB  - Tracheal stenosis following prolonged intubation is a relatively rare but a
      serious problem. However, some degree of airway injury is common following
      intubation, no matter whether it is prolonged or of short duration. Here, we are
      reporting a fifty six year old male patient who developed multiple web like
      tracheal stenosis following intubation with high volume low pressure cuff
      endotracheal tube. Subsequently, the stenosis was successfully dilated by balloon
      bronchoplasty.

PMID- 19742267
TI  - Biological agents targeting beyond TNF-alpha.
AB  - Biological agents represent an important addition to the therapies for immuno
      inflammatory conditions and have a great impact on the disease course and quality
      of life of these patients. However, recent reports of serious infections like
      tuberculosis, demyelinating and neurodegenerative diseases, pancytopenia,
      cardiovascular diseases, etc. after anti-TNF therapy raised questions on their
      safety. Hence, focus is shifted towards drugs targeting cytokine checkpoints in
      the inflammatory cascades beyond TNF-alpha. Existing therapeutic targets include
      the biological agents acting as antagonists of various inflammatory cytokines
      (Anakinra, Tocilizumab, Atlizumab) and modulators of CD80 or CD86-CD28 co
      stimulatory signal (Abatacept), CD2 receptors on T-cells (Alefacept), CD11a,
      subunit of leukocyte function-associated antigen 1 (Efalizumab), vitronectin
      receptor and CD20 antigen on pre-B, immature and mature B cells (Rituximab). With
      the introduction of these novel molecules the future for immunomodulatory
      intervention in rheumatology, asthma, crohn's disease, septic shock etc. looks
      very promising. These novel therapeutic agents could truly give a new hope to the
      clinician to modify the disease and achieve tangible improvements in the lives of
      the patients.

PMID- 19742268
TI  - Cerebral malaria caused by Plasmodium vivax in adult subjects.
AB  - Cerebral malaria is a diffuse encephalopathy associated with seizures and status
      epilepticus which can occur in up to one-third of patients with severe malaria,
      particularly that caused by Plasmodium falciparum. In this article, we report
      three cases of Plasmodium vivax malaria (all adult male patients) complicated by
      seizures and symptoms of diffuse meningoencephalitis. Two patients had
      predominantly meningeal signs, while in the third patient the features were
      purely of encephalitis All cases were treated with artesunate. Usually, cerebral
      malaria is caused by P. falciparum, and rarely, cerebral malaria is a presenting
      complication or occurs during the course of P. vivax infection.

PMID- 19742269
TI  - Clinical course and spectrum of intensive care unit patients reactivating herpes
      simplex-1 virus: a retrospective analysis.
AB  - BACKGROUND: Herpes simplex-1 virus (HSV-1) reactivation in the respiratory tract
      is common in intensive care unit (ICU) patients. However, susceptible ICU
      populations are poorly defined. Clinical recognition of HSV infection of the
      respiratory tract is difficult and the impact of such reactivation is not
      understood. MATERIALS AND METHODS: A retrospective analysis of HSV-1 positive
      patients encountered over a 5-year period at a multispecialty ICU was carried
      out. HSV-1 was identified in respiratory secretions using a qualitative
      polymerase chain reaction (PCR) technique. Patient charts were reviewed for
      clinical features that would typify HSV-1 respiratory involvement, and the
      morbidity and mortality risks found with HSV-1 respiratory involvement. RESULTS:
      A review of 48 HSV-1 positive ICU patients showed that patients reactivating HSV
      in the respiratory tract fell into one of the three categories: (1) septic
      elderly patients with and without ARDS, (2) immunosuppressed patients, especially
      those receiving high-dose steroids, and (3) post-thoracotomy patients.
      Abnormalities suggestive of HSV-1 reactivation in the respiratory tract included,
      haemorrhagic or excessive respiratory secretions, concomitant orofacial herpes
      (42%), and bronchoscopic abnormalities (hemorrhagic ulcers and mucosal
      friability) (83%). Twenty eight percent of the HSV-1 infected patients
      experienced postextubation stridor. HSV-1 reactivation was associated with
      extended ventilator stays, significant mortality (42%), and ventilator-associated
      pneumonias (52%). CONCLUSIONS: Identification of susceptible populations and
      definition of clinical features of HSV-1 related respiratory disease can enable
      diagnosis of HSV-1 infection in ICU patients. Although detection by a PCR
      technique can rapidly diagnose HSV-1 reactivation, prospective studies are
      required to clarify HSV disease versus mere shedding, and understand the impact
      of HSV-1 reactivation in hospitalized patients.

PMID- 19742270
TI  - Safety and efficacy of polymyxin B in multidrug resistant Gram-negative severe
      sepsis and septic shock.
AB  - BACKGROUND AND AIMS: The emergence of multidrug resistant strains of Gram
      negative bacteria, especially the lactose nonfermenters like Pseudomonas and
      Acinetobacter, in the intensive care units have prompted renewed worldwide
      interest in the polymyxins. However, perceived nephrotoxicity has been a major
      vexation limiting their early and regular use in severe sepsis. This study was
      conducted to assess the safety and efficacy of polymyxin B in patients with
      severe sepsis and septic shock. MATERIALS AND METHODS: Forty-five patients with
      sepsis admitted in our medical-surgical intensive care units were identified from
      pharmacy records to have received polymyxin B. We retrospectively reviewed the
      clinical and microbiologic outcomes as well as occurrence of renal failure
      temporally related to the use of intravenous polymyxin B. RESULTS: polymyxin B
      was used in severe sepsis and septic shock with the isolated organism being
      resistant to other available antimicrobials or clinical deterioration despite
      carbapenem use. Overall mortality was 52% and among patients who received at
      least eight days of intravenous polymyxin B, 67% patients with initial septic
      shock and 62% with severe sepsis survived. The target multidrug resistant
      organism was cleared in 88% of subjects evaluated by repeat microbiologic
      testing. Acute renal failure developed in only two patients (4%). CONCLUSIONS:
      Polymyxin B has acceptable effectiveness against nosocomial multidrug resistant
      Gram-negative sepsis. The associated nephrotoxicity has been found to be
      significantly lower than previously reported even in patients with background
      renal impairment and established risk factors of renal failure.

PMID- 19742271
TI  - Diagnostic instruments.

PMID- 19742272
TI  - Subjective health in older people.
AB  - The Nottingham Health Profile (NHP [1]) is a widely used instrument to measure
      subjective health in clinical research. However, there are no age-specific norms
      for older adults in Germany. The present study was conducted to analyze the
      psychometric properties of the German version of the Nottingham Health Profile
      (NHP) in older people. Age-specific reference values for the elderly are
      presented. Subjects were drawn from the general population of older German people
      aged 61 to 95 years (n=630; mean age 69.5 years; 55.7% female). Five of the six
      NHP scales revealed a good internal consistency (.70<=alpha<=.92). The subscales
      (with the exception of the subscale social isolation) showed moderate relations
      with instruments measuring somatization disorders and subjective body complaints
      (Screening for Somatoform Disorders SOMS [2]); Giessen Subjective Complaints List
      GBB-24 [3]). Compared to younger subjects, subjective health decreases with age.
      Therefore age-specific reference data for older people are necessary.
      Differential reference data are reported for four age groups above 60 years of
      age and for male and female older people. The outcome confirms that the NHP is a
      reliable, valid instrument to measure subjective health in older people.

PMID- 19742273
TI  - What do patients think after a lung transplantation about their self, lung and
      social network? A quantitative analysis of categorical interview data.
AB  - OBJECTIVE: Psychosocial aspects have been investigated in transplant medicine
      mainly by the means of various structured questionnaires. To date only few
      interview data are available on patients thoughts about their self, the
      transplanted lung or the medication, and the relationship between these thoughts
      and compliance or gender. METHODS: Twenty patients were interviewed after
      transplantation about their perceptions on self, body, transplanted lung,
      medication and social network. Their compliance was rated by the attending
      physicians. The overall interrater-reliability for the category groups was
      Kappa=.8. The article presents quantitative results of the content analysis.
      RESULTS: Statements were made most frequently about the patients' social network
      and their self, and significantly less frequently about their body, lung and
      medication. "Closeness", "distance" and "depression" where main issues that these
      patients were dealing with. "Closeness" and "distance" played major roles in
      interpersonal relationships as well as in the relationship to the new lung.
      Depression mainly had to do with health burdens and the psychosocial consequences
      of the transplantation (e.g. financial worries). Women made significantly more
      statements about their social network than men; furthermore they formulate more
      accented emotional evaluations. Patients with low compliance were more frequently
      preoccupied with their self, their body as well as the experience of "dependence"
      and "achievement" than patients with high compliance; also low compliant patients
      made more critical statements. CONCLUSIONS: For lung transplant recipients social
      relationships are the prime topic of their daily experience. With respect to
      compliance behaviour, special attention should be paid to the patients' self and
      body perception as well as to their experience of dependence. These results
      should be confirmed in studies with larger sample sizes.

PMID- 19742274
TI  - Screening for affective and anxiety disorders in medical patients - comparison of
      HADS, GHQ-12 and Brief-PHQ.
AB  - OBJECTIVES: The detection of patients with comorbid mental disorders is of high
      clinical importance. Screening instruments can be recommended for early
      recognition. This study investigates the discriminant validity of the Hospital
      Anxiety and Depression Scale (HADS), General Health Questionnaire (GHQ-12) and
      Patient Health Questionnaire (Brief-PHQ-D) in chronically ill patients. METHODS:
      Two hundred and four patients with chronic illness participated in a two-stage
      survey. First patients were screened with HADS, Brief-PHQ and GHQ-12 and then
      examined for mental disorders by clinical standardized interview (M-CIDI).
      Validity of the three instruments was compared using ROC(receiver operating
      characteristics)-analysis and CIDI-diagnoses as criteria. RESULTS: The Brief-PHQ
      and the HADS performed better than GHQ-12 concerning affective and anxiety
      disorders without reaching significance. Even though the Brief-PHQ performs
      significantly better in the category of "any mental disorder", the differences
      between the Brief-PHQ and the HADS remain not significant considering anxiety and
      affective disorders. The Brief-PHQ performed slightly better considering
      depressive disorders with an area under the curve (AUC) of 0.844, a sensitivity
      of 80% and a specifity of 75.7%. CONCLUSIONS: Screener can be used for the
      detection of mental disorders in patients with chronical illness. Especially the
      Brief-PHQ and the HADS can be recommended considering sensitivity and specifity.
      An advantage of the Brief-PHQ is the ability of categorial and dimensional
      analysis.

PMID- 19742276
TI  - Typological and dimensional approach at comparing the Giessen Test (GT) with the
      NEO-Five-Factor-Inventory (NEO-FFI).
AB  - OBJECTIVES: This article reports comparisons of the Giessen Test (GT) with the
      NEO-Five-Factor-Inventory (NEO-FFI) based on a dimensional as well as on a
      typological approach. METHOD: Data were collected from 1673 subjects (aged
      between 18 and 96 years) constituting a representative sample of the German
      population. RESULTS: The results indicate only moderate agreement (ranging from
      .25 to .61) between the subscales of the two personality inventories. The
      correspondence seems to be somewhat higher, when the typological approach was
      used instead of the dimensional approach. CONCLUSIONS: The typological approach
      is less dependent on the underlying questionnaires and provides a useful
      extension of the dimensional approach.

PMID- 19742275
TI  - Post-operative delirium after hip fracture treatment - a review of the current
      literature.
AB  - Delirium is a common accompaniment of physical illness in old age, affecting
      approximately one out of five of those admitted to medical wards, the number
      being higher for elderly with fractured femurs. Although its existence has long
      been recognized its exact pathophysiology has not yet been fully elucidated. The
      present article presents up-to-date information concerning the etiology,
      pathophysiology, prevention and treatment of the post-operative delirium after
      hip-fracture treatment. The fact that its diagnosis remains mainly clinical
      requiring a high index of suspicion, both from nursing and medical staff, results
      in important under-recognition of the syndrome. Delirium is a medical emergency
      and if not promptly and urgently treated, or even better prevented, may have
      serious consequences for the patient and the family members. Proper measures for
      its prevention and treatment result in shorter hospital stay of the patients,
      less financial cost and better surgical outcome and rehabilitation of the elderly
      patient.

PMID- 19742277
TI  - Self-efficacy in acutely traumatized patients and the risk of developing a
      posttraumatic stress syndrome.
AB  - Post traumatic stress disorder (PTSD) occurs across 15-20% of victims suffering
      physical injury. The occurrence of PTSD has been attributed to both the trauma
      and the victim's individual resources, such as resilience, coping strategies, and
      social support systems. In the present study, we explored the role of self
      efficacy for cognitive self-regulation in the posttraumatic adaptation process of
      sixty-five patients immediately following trauma (T1) and approximately four
      months later (T2) assessing posttraumatic stress syndrome according to DSM-IV
      criteria. We hypothesized perceived self-efficacy as a predictor for an increased
      risk of developing posttraumatic stress symptoms. Self-efficacy measured
      immediately following trauma correlated significantly with the development of
      posttraumatic stress syndromes. This finding suggests that the evaluation of
      cognitive adaptation to trauma is a helpful marker for clinical outcome
      assessment and can therefore be used for the identification of patients needing
      psychotherapeutic intervention.

PMID- 19742278
TI  - Analysis and development of multiprofessional teams in medical rehabilitation.
AB  - Team analysis and team development are important instruments of organizational
      development and quality management. They contribute to team optimization in
      medical rehabilitation. Team analysis allows assessment of strengths and
      weaknesses of teams, resulting in possible recommendations for team development.
      So far there are only a few empirical studies and little practical experience
      analyzing multiprofessional teams in the health care field and inpatient medical
      rehabilitation in particular. This article presents team analyses performed on
      twelve multiprofessional medical rehabilitation teams in Germany and
      corresponding recommendations for team development. A heuristic model of team
      analysis and team development was designed for this purpose. The model comprises
      the following parameters: input (team structure), process (teamwork) and output
      (team success). Variables to measure these parameters were derived from team
      performance models and known weaknesses of teams in medical care. Team analyses
      were conducted by administering a semi-standardized interview form and a short
      questionnaire to the head physicians of participating clinics while a survey was
      administered to all members of the rehabilitation team. The results of the team
      analyses suggested the use of team development measures on each team. The teams
      were classified into three categories by their need for team development (low,
      medium and high). Furthermore five modules of team development could be generated
      from the results of the team analyses: (1) executive coaching, (2) communication
      training, (3) changing attitude towards teamwork, (4) task-oriented team
      development, and (5) training on socio-integrative aspects of teamwork. Some of
      these modules are important constituents of quality management programs. Team
      development can facilitate quality management programs, particularly with regard
      to process and output relating to leadership and staff. The study shows, that
      there is a basic, yet variable need of team analysis and team development in the
      medical rehabilitation facilities.

PMID- 19742279
TI  - Psychosocial determinants for frequent primary health care utilisation in
      patients with heart failure.
AB  - OBJECTIVE: Psychosocial symptoms are common in patients with heart failure.
      Little research, however, has been done to determine which psychosocial factors
      influence primary care patients' consultation frequency in the case of heart
      failure. METHODS: We recruited 310 primary care patients with heart failure by
      analysing electronic patient records. At baseline, psychological distress
      (anxiety and depression; HADS), disease coping (FKV), negative affectivity and
      social inhibition (DS-14), disease-specific quality of life (MLHFQ) and social
      support (F-SozU) were measured by validated questionnaires. Severity of heart
      failure (according to NYHA-classification and Goldman's Specific Activity Scale)
      and sociodemographic characteristics were documented by self-report instruments.
      Nine month later, patients were contacted by telephone in order to assess GP
      consultation frequency. Logistic regression was done to determine whether these
      psychological, medical and sociodemographic factors were associated with primary
      care utilisation. RESULTS: On average, patients consulted their general
      practitioner (GP) 8.2 times during nine months. Female subjects and patients with
      higher levels of perceived heart failure severity, physical problems and anxiety
      or depression as well as those living alone visited their GP significantly more
      often. In multivariate analysis, frequent attendance in general practices was
      predicted by physical problems and living alone. These factors explained 11.6% of
      the variance of frequent attendance in general practices. CONCLUSION:
      Psychosocial factors of help-seeking behaviour in heart failure patients focus on
      mental and physical discomfort and a lonely home situation. These factors might
      need to be compensated by GP consultation. GPs should address the rearrangement
      of physical, mental, and social resources to strengthen self-reliance of patients
      with heart failure.

PMID- 19742280
TI  - In-patient, short-term group psychotherapy - a therapeutic option for Bundeswehr
      soldiers?
AB  - OBJECTIVE: This study is to assess the efficacy of short-term group psychotherapy
      rooted in depth psychology for Bundeswehr soldiers suffering from depressive,
      neurotic, stress, or personality disorders. METHOD: 103 participants in the in
      patient, closed group setting were evaluated prospectively and compared with a
      non-randomized waitlisted control group. RESULTS: In all relevant SCL-90-R
      (Symptom-Check-List-90) and MMPI-K (Minnesota-Multiphasic-Personality-Inventory
      short-form) scales therapy resulted in significant improvements as compared with
      the initial values. The control group did not show any significant changes, the
      therapy group was significantly superior to the control group in the scales of
      MMPI-K and the GSI-Scale of the SCL-90-R. For soldiers with a stress-reactive
      disorder (F43), no differences in efficacy could be identified compared with the
      other diagnosis groups. CONCLUSION: The results were considered to indicate that
      in-patient, short-term group psychotherapy may, in combination with additional
      setting components, be helpful in improving psychological symptoms in German
      soldiers. The indication range of group therapy offered to Bundeswehr soldiers
      should be expanded to also include primary prophylaxis and the treatment of
      mental-health problems following deployments abroad, if applicable.

PMID- 19742281
TI  - Symmetries in a standardized set of emotional facial expressions (JACFEE).
AB  - OBJECTIVE: To investigate possible asymmetry in a widely used set of standardized
      emotional facial expressions (JACFEE, Japanese and Caucasian Facial Expressions
      of Emotion). METHOD: Chimeric pictures with either two left (LL) or two right
      (RR) halves of the emotional face were produced from the original set and
      presented to healthy subjects who rated their intensity. RESULTS: With the
      exception of "happiness", for all other emotions (sadness, disgust, anger, fear
      and surprise) LL and RR composites were given comparable intensities, speaking
      for high symmetry in the faces. CONCLUSIONS: The JACFEE facial emotion pictures
      are mostly symmetrical, possibly due to their standardisation procedure when
      producing the pictures.

PMID- 19742282
TI  - Evaluating patients' preferences for multiple myeloma therapy, a Discrete-Choice
      Experiment.
AB  - BACKGROUND: While there is an increasing emphasis on patient empowerment and
      shared decision making, patients' preferences for attributes associated with
      their treatment still need to be measured and considered. In the present study,
      patients' preferences regarding treatment of multiple myeloma (MM) were explored
      using direct assessment and a Discrete-Choice-Experiment (DCE). PATIENTS AND
      METHODS: After reviewing the literature about preferences of myeloma patients we
      conducted a qualitative study with three focus groups consisting of six to eight
      MM-patients each. In order to achieve content validity, we aimed at collecting
      all relevant factors for an ideal MM-treatment. In a subsequent quantitative
      study phase, data was collected in an online or paper-pencil self-completed
      questionnaire. It included sociodemographic data, self-rated health (SF12v2
      variation) and patients preferences of therapy characteristics using direct
      measurement (16 items on a five-point Likert-scale) as well as a Discrete-Choice
      Experiment (DCE, eight pairs with eight characteristics). RESULTS: 282 patients
      answered the questionnaire; 46% female, age: mean 62 yrs (SD=10 years), duration
      of MM: 5 yrs (SD=3.8 years). Direct measurement showed effectiveness aspects
      (i.e. high effectiveness, long lasting effects, max. prolonged life expectancy)
      and further treatment options in the first places, followed by maximal prolonged
      life expectancy, minor side effects and therapy-free-intervals. In the DCE,
      alternatives with further treatment options, longer life expectancy, "not always
      think of the disease" and therapy-free-intervals were more likely to be chosen,
      giving thus similar results. CONCLUSION: Besides prolongation of life expectancy
      and effectiveness of treatment, further treatment options are of foremost
      importance to multiple myeloma patients. In addition, therapy-free intervals as
      well as an improved emotional quality of life ("Not always think of the disease")
      are valued as very important. The combination of direct assessment of importance
      and DCE is a valid combined survey technique for eliciting preferences of
      patients with multiple myeloma. The former ensures content validity (the
      possibility to measure a longer list of potentially important aspects), the
      latter has the advantage to combine positive and negative therapy characteristics
      and to avoid the problem of ceiling effects and "all-is-important" results.

PMID- 19742283
TI  - The symptom checklist-27-plus (SCL-27-plus): a modern conceptualization of a
      traditional screening instrument.
AB  - BACKGROUND: The symptom checklist SCL-27-plus is a short, multidimensional
      screening instrument for mental health problems. It contains five scales on
      current symptoms: depressive, vegetative, agoraphobic, and sociophobic symptoms
      and pain; a global severity index (GSI-27); a lifetime assessment for depressive
      symptoms; and a screening question for suicidality. METHOD: A reformulated
      version of screening items constituted a survey of n=374 students. Therefore, a
      total of 76 items was formulated and presented to the students within a
      questionnaire booklet, that could be filled out at home. RESULTS: All scales of
      the SCL-27-plus showed good to satisfactory reliability (i.e. .90 >= Cronbach's a
      >= .70). The distributions of the scales were less skewed than in older versions
      of the symptom checklists and scale inter-correlations were lower. The scale
      "symptoms of mistrust" could not be retained. CONCLUSION: The SCL-27-plus
      demonstrates a clear improvement over the SCL-27. Test-statistical properties
      were improved. In addition, the supplementation by a lifetime scale for
      depression and a screener for suicidality shall help the clinician as well as the
      epidemiologist.

PMID- 19742284
TI  - Using artwork to understand the experience of mental illness: Mainstream artists
      and Outsider artists.
AB  - OBJECTIVE: Artwork and psychiatric disorders are often linked. Accomplished
      artists with psychiatric disorders express themselves and their emotional
      distress through their works, and art therapists use the visual arts to help
      clients understand their problems and cope with them. There have been a number of
      psychiatric patients with no previous art training who produced artwork that many
      consider museum-worthy (Art Brut, or Outsider Art.) For the past two years, I
      have used artwork in another way: to better understand my clients and their
      psychiatric disorders. METHODS: Presented here are paintings I have made about
      the mental illness experience of some of my clients, all well known to me through
      their therapy. It is a form of visual psychodrama, in which I reverse roles with
      the client through the paintings. My goal has been to experience the stresses
      felt by my clients so that I can understand them better. RESULTS: The paintings
      have served as a point of embarkation for therapy sessions, as a means of
      clarifying a client's experience, and as a way to show clients that their
      therapist is attending to what they say. Countertransference undoubtedly plays a
      role in my choice of clients and their portrayals, but the intent is to help me
      better understand the clients' experiences.Included here are images of some of
      these paintings with a short psychiatric history of the client about whom they
      were made. Accompanying each one are responses from the clients upon viewing
      "their" paintings, and a discussion of the client's psychiatric disorder.
      CONCLUSIONS: Making these paintings has helped me understand better the feelings
      of isolation, rejection, loss, and alienation that many of my clients experience
      every day. In turn, they tell me that viewing the paintings is an intense
      experience for them as well. As an outsider artist, I must leave it to the viewer
      to determine whether or not these paintings qualify as "art."

PMID- 19742285
TI  - Long-term course of psychiatric disorders in cancer patients: a pilot study.
AB  - BACKGROUND: About one third of cancer patients suffer from a psychiatric
      disorder. However, only few studies feature long-term assessment of psychiatric
      disease in cancer patients, covering a broad range of diagnoses, and employing
      high-quality instruments. PATIENTS AND METHODS: A total of 62 patients underwent
      assessments during a 3-year follow-up period after initial cancer diagnosis. The
      Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders was
      administered to measure psychiatric morbidity at baseline (t1) and two follow-ups
      (t2 and t3). Follow-up assessments took place from 6 to 18 months (t2) and from
      24 to 36 months (t3) after baseline. Biomedical and psychosocial factors were
      evaluated to identify predictors of psychiatric disorders using univariate and
      multivariate analyses. RESULTS: At t1, at least one DSM-IV diagnosis was found in
      29% of the cases. At follow-ups, the frequency of psychiatric morbidity increased
      to 36% at t2 and 44% at t3, respectively. New occurrence of psychiatric disease
      at follow-ups was 18% at t2, and 38%, at t3. Predictors of psychiatric disorders
      were low social support, low physical functioning, metastases, complications of
      disease, and loss of sportive activity. CONCLUSION: Persistence and amount of
      newly diagnosed psychiatric disorders during three years after cancer treatment
      should be considered in the treatment of cancer patients, especially in
      individuals with accordant predictive factors.

PMID- 19742286
TI  - Medical and licit drug use in an urban/rural study population with a refugee
      background, 7-8 years into resettlement.
AB  - OBJECTIVE: Research into medical and licit drug use in resettled refugee
      populations is scarce, despite the fact that mental health status often has been
      found to be poorer than in general populations. Hence the aim of this study was
      to estimate the prevalence of self-rated use of medicine and licit drugs among
      adults who came to Sweden from Bosnia-Herzegovina (1993/94) and who in 2001 were
      living in either an urban (low employment context) or a rural (high employment
      context) region (n=4185). METHODS: Prevalence was estimated from a cross
      sectional questionnaire distributed to a representative sample (n=650) in 2001
      (63.5% response rate). RESULTS: The study population estimates of usage of
      sedatives (26.5%), sleeping tablets (26.2%) and antidepressants (22.3%) did not
      differ by gender but did so by region, with a higher urban prevalence. The
      consumption of alcohol (5.1%) and cigarettes (41.0%) did not differ by region but
      men reported higher alcohol consumption than women. CONCLUSION: The high
      consumption of medicine (compared with general populations) raises the question
      of treatment efficiency and the need for public health attention and evaluation
      many years after resettlement. Factors to consider for further research with
      analytic prerequisites concern indications that regional differences may be
      influenced, not only by urban employment being lower but also by urban/rural
      differences in prescription rates and/or access to health care; moreover, there
      might have been a selection to the urban region of older people, with a more
      vulnerable family situation, and/or poorer mental health. Finally, the overall
      alcohol (low) and cigarettes (high) consumption in the study population followed
      prevalence patterns found in Bosnia-Herzegovina rather than in Sweden.

PMID- 19742287
TI  - MATRIX - development and feasibility of a guide for quality assessment of patient
      decision aids.
AB  - Decision aids (DAs) are interventions designed to help people make specific and
      deliberative choices among options by providing information about the options and
      outcomes that is relevant to a person's health status.There is an ongoing
      discussion about the quality of DAs. The present article provides an overview on
      systematic approaches using various quality criteria. However, these evaluation
      guides are not yet implemented. Up to now quality assessment of DAs is often
      limited to the evidence on efficacy through controlled trials using single
      outcome measures. Since DAs are multi-component interventions, single-outcome
      trials are not sufficient for complete quality assessment. Consideration of
      theoretical founding and the development process is required. In an earlier paper
      we proposed a novel concept of quality to meet this challenge. We introduced
      MATRIX a guide for quality assessment of DAs aimed at disclosing the rationale
      behind underpinning theories, methods, and goals of a DA. The present paper
      reports how the development of MATRIX progressed including results of pre-testing
      and a feasibility study. We present the revised version of MATRIX, explain its
      basic concept, and describe the way to use it.

PMID- 19742288
TI  - The acquiescence effect in responding to a questionnaire.
AB  - OBJECTIVE: Since the acquiescence effect can distort assessments, it is important
      to test techniques to quantify this effect. METHODS: The tendency of acquiescence
      is tested by means of a questionnaire. 2037 representatively selected subjects
      filled in the Multidimensional Fatigue Inventory (MFI-20), which consists of five
      subscales with positively and negatively formulated items. For each subject and
      for each subscale an acquiescence score was calculated based on the simple sum of
      the answers to the items of both orientations. RESULTS: Extreme acquiescence
      scores were rare (about 0.5%). All correlations between the acquiescence scores
      of the subscales were positive with mean values of 0.24, which indicates a
      certain degree of individual consistency in the acquiescence behavior. In the
      exploratory and confirmatory factorial analyses the polarity of the items was at
      least as meaningful as the contents of the subscales. Persons with high degrees
      of acquiescence were principally older and more depressed. By means of Rasch
      scaling procedures differences in threshold parameters for the response
      categories between positively and negatively oriented items were found.
      CONCLUSION: The acquiescence scores derived by simple addition of item values
      proved to be well suited to clarify amount and conditions of the acquiescence
      effect.

PMID- 19742289
TI  - Living with a partner and health care use - results from the MONICA survey
      Augsburg in Southern Germany.
AB  - OBJECTIVE: Several studies have shown that social relationships are associated
      with health care use. This study aims to test if and to which extent a proximal
      element of social relationships, particularly living together with a partner,
      influences the health care utilisation in the same way as a distal element such
      as group membership. METHODS: On the basis of a representative random sample of a
      southern German population (4856 participants), the associations were assessed
      between the following groups of variables: number of consultations with the
      general practitioner or internists, type of social relationships (living with a
      partner, friends, relatives, group memberships), need (evaluated and perceived
      health status), socio-demographic variables. RESULTS: All analyses showed
      associations between living with a partner and health care utilisation.
      Individuals living with a partner had lower levels of utilisation than
      individuals not living with a partner (mean: 4.3 vs. 5.2). These associations
      persisted after controlling for socio-demographic and need variables. For the
      other indicators of social relationships, though, there were no significant
      associations with outpatient visits. CONCLUSIONS: Distinguishing between
      different types of social relationships is important for disentangling the
      overall effects of social relationships on health care utilisation. Also, the
      empirical findings confirm that health care research should not be restricted to
      medical variables, but should also include psycho-social factors.

PMID- 19742290
TI  - Antonovsky's Sense of Coherence in psychosomatic patients - a contribution to
      construct validation.
AB  - OBJECTIVE: The objective of the present study is to contribute towards the
      validation of the SOC (Sense of Coherence) construct on the basis of data from
      psychosomatic patients. METHOD: The study included a total of 1403 patients
      treated as out-patients or in consultations in the Clinic for Psychosomatic
      Medicine at the Charite University of Medicine, Berlin, between July 2002 and
      October 2005. Correlations were tested between the sense of coherence (SOC-L9),
      sociodemographic variables and the following psychometric instruments: Patient
      Health Questionnaire (PHQ), Brief COPE, Questionnaire on Self-Efficacy, Optimism
      and Pessimism (SWOP-K9) and Perceived Stress Questionnaire (PSQ-20). RESULTS:
      Associations were found between sense of coherence and age, but not with gender.
      In addition, high sense of coherence was correlated with high self-efficacy,
      optimism, subjective physical well-being and favourable coping strategies as well
      as with low perceived stress. CONCLUSION: The results contribute to the
      validation of the SOC construct. Future investigations should include
      longitudinal studies of the precise association between sense of coherence and
      other psychological variables.

PMID- 19742291
TI  - A German version of the Shedler-Westen Assessment Procedure (SWAP-200) for the
      dimensional assessment of personality disorders.
AB  - THEORETICAL BACKGROUND: The traditional diagnosis of personality disorders has
      been criticized for lack of empirical support, reliance on categorical
      classifications and low validity. OBJECTIVE: A German version of the Shedler
      Westen Assessment Procedure (SWAP-200) is presented. This Q-Sort procedure is
      well-established in the USA and facilitates the dimensional diagnosis of
      personality pathology in accordance with DSM-IV. In addition, a taxonomy of
      personality has been derived using factor analyses. METHODS: The SWAP-200 was
      applied to 18 patients on the basis of semi-structured interviews. Interviewer
      ratings were correlated with the SWAP-200 completed by an independent observer
      and the patients' therapists. RESULTS: Good inter-rater reliability (between
      r=.69 and r=.76) was found. While average convergent validity coefficients
      between interviewer, observer and therapist were satisfactory (between r=.54 and
      r=.68), outliers were observed. RESULTS suggest that the factor analytically
      derived taxonomy may be more valid.

PMID- 19742292
TI  - Ambivalence over Emotional Expressiveness: psychometric evaluation of the AEQ-G18
      in a representative German survey.
AB  - OBJECTIVE: The present study evaluates a questionnaire on ambivalence over
      emotional expressiveness, the AEQ-G18 [1], [2], with regard to its statistical
      parameters, the influence of socio-demographic variables, and its
      interrelationship with depression and quality of life. METHODS: A representative
      German sample (1009 participants from East Germany and 1034 participants from
      West Germany) completed the AEQ-G18 [1], [2], the depression screener DEP-2 [3],
      the Profile of Mood States POMS [4], the revised Beck Depression Inventory BDI
      [5], the short form of the Patient Health Questionnaire PHQ-9 [6] and the SF-36
      health survey questionnaire [7]. RESULTS: Our study was only partially able to
      confirm the two factors effect ambivalence and competence ambivalence postulated
      by Traue et al. [1], [2]. Women scored somewhat higher on the scale effect
      ambivalence. Participants with a higher educational background exhibited less
      emotional ambivalence. Emotional ambivalence correlated positively with
      depression and reduced psychological state of health (depression, fatigue, and
      anger), whereas it correlated negatively with health-related quality of life and
      positive attitude (vigor). In addition to the scales of the AEQ-G18, we developed
      a short form, the AEQ-G10, and provide normative data for the AEQ-G18 and the AEQ
      G10. CONCLUSION: This study presents normative data for two variations of a
      clinically relevant, valid, and time-efficient diagnostic instrument used for the
      evaluation of ambivalence over emotional expressiveness, the AEQ-G18 and its
      short form, the AEQ-G10.

PMID- 19742293
TI  - Suicide attempts and retrospective reports about parent-child relationships:
      evidence for the affectionless control hypothesis.
AB  - OBJECTIVE: To compare the characteristics of recalled parent-child relationships
      in suicide attempters vs. non-attempters METHODS: A total of 509 patients - 249
      presenting with pain at a psychosomatic clinic and 260 from the offices of
      general practitioners - were interviewed retrospectively about suicide attempts
      and parent-child relationships. RESULTS: The overall rate of those reporting a
      suicide attempt was 17%. Bivariate analyses showed associations of poor parent
      child relationships with suicide attempts throughout. In a multivariate analysis,
      the combinations high maternal control*low perceived love (p<.001) and high
      control*high role reversal (p=.002) were associated with particularly elevated
      risks for suicide attempts. CONCLUSION: Beside the two most extensively explored
      dimensions of parent-child relationships, parental affection and control, one
      other dimension, role reversal, also contributes strongly to risk for offspring
      suicide attempts and should be considered in future studies.

PMID- 19742294
TI  - Diagnostic instruments for behavioural addiction: an overview.
AB  - In non-substance-related addiction, the so-called behavioural addiction, no
      external psychotropic substances are consumed. The psychotropic effect consists
      of the body's own biochemical processes induced only by excessive activities.
      Until recently, knowledge was limited with respect to clinically relevant
      excessive reward-seeking behaviour, such as pathological gambling, excessive
      shopping and working which meet diagnostic criteria of dependent behaviour. To
      date, there is no consistent concept for diagnosis and treatment of excessive
      reward-seeking behaviour, and its classification is uncertain. Therefore, a clear
      conceptualization of the so-called behavioural addictions is of great importance.
      The use of adequate diagnostic instruments is necessary for successful
      therapeutical implications.This article provides an overview of the current
      popular diagnostic instruments assessing the different forms of behavioural
      addiction. Especially in certain areas there are only few valid and reliable
      instruments available to assess excessive rewarding behaviours that fulfill the
      criteria of addiction.

PMID- 19742295
TI  - Perceived self-competence and relationship experiences in inpatient psychotherapy
      - a pilot study.
AB  - OBJECTIVE: The patient's sense of capability in mastering future challenges
      ("self-competence") represents an important therapeutic target. To date,
      empirical findings concerning the influence of the therapeutic relationship on
      perceived self-competence remain scarce. Against this backdrop, mutual
      associations between perceived self-competence, symptom distress and various
      relationship experiences within inpatient psychotherapy are investigated.
      METHODS: 219 inpatients with heterogeneous diagnoses completed the SCL-90-R, the
      Relationship Questionnaire RQ1 and the Inventory of Interpersonal Problems IIP
      prior to therapy. Self-competence and relationships to the individual therapist,
      therapeutic team and fellow patients were assessed weekly using an inpatient
      questionnaire (SEB). RESULTS: As expected, there were significant negative
      correlations between self-competence and symptom distress. Patients with more
      "fearfully avoidant" behavior upon admission experienced relationships during
      therapy as significantly more negative. Conversely, the quality of relationships
      to the individual therapist and fellow patients was predictive of a significant
      part of variance in self-competence upon discharge. CONCLUSIONS: A model of
      mutual interactions is proposed for the variables under investigation. RESULTS
      suggest that the positive association between the therapeutic relationship and
      symptom reduction could partly be explained by an improvement in perceived self
      competence.

PMID- 19742296
TI  - Hope as an emotion of expectancy: first assessment results.
AB  - THEORETICAL BACKGROUND: Based on deficiencies of present conceptions of hope, an
      appraisal model is proposed as an alternative approach, in which hope is defined
      as the expectancy that a possible event, which a person rates positively, will
      occur in the future. The event depends both on situational and internal factors.
      This model differentiates between a subjective probability of occurrence and a
      subjective probability of affiliation. The first refers to a person's estimation
      of the probability that a positive event can occur in general (e.g. the chances
      of recovering from a life-threatening illness); the second refers to the
      estimated probability that he/she belongs to those, for which the positive
      outcome is likely. OBJECTIVE: The present contribution is a first validation of
      the appraisal model of hope. METHODS: On a sample of prisoners (N=172) the degree
      of hope never to be incarcerated again after serving the present sentence was
      tested. Furthermore, personality dimensions, psychological distress, perceived
      social support and features of childhood delinquency were assessed using
      questionnaires. RESULTS: As expected, the results indicate that both probability
      estimations are largely independent of each other and were predicted by different
      factors (such as duration of arrest, anxiety, social support, or childhood
      delinquency).

PMID- 19742297
TI  - Measuring subjective health in children and adolescents: results of the European
      KIDSCREEN/DISABKIDS Project.
AB  - OBJECTIVES: Currently there is a lack of information regarding the health-related
      quality of life (HRQoL) of healthy as well as chronically ill children on a
      European level. In 2 European projects questionnaires for the assessment of the
      HRQoL in children and adolescents have been developed: The KIDSCREEN project aims
      at a co-operative European development of a standardised screening instrument for
      children's HRQoL for the implementation in representative national and European
      health surveys. In the DISABKIDS project a chronic-generic questionnaire as well
      as modules for specific conditions (e.g. asthma) were developed for children with
      chronic conditions. METHODS: Both projects shared similar steps: 1. Development
      phase, in which the items were generated and tested, 2. Survey and Field phase,
      in which the modified questionnaires were tested with healthy and chronically ill
      children and adolescents in national representative surveys, and 3.
      Implementation phase in national health surveys or clinical studies. RESULTS: In
      the sister projects, the KIDSCREEN instrument was tested in 22,830 children and
      the DISABKIDS instrument in 1605 chronically ill children. The current paper
      describes the development and pilot-testing as well as psychometric results of
      the field tests of both studies. CONCLUSION: The KIDSCREEN/DISABKIDS instruments
      make it possible to assess generic, chronic-generic and disease-specific aspects
      of quality of life in children and present an innovative approach to
      intercultural HRQoL assessment in health research.

PMID- 19742298
TI  - The Amsterdam Preoperative Anxiety and Information Scale (APAIS) - the first
      trial of a German version.
AB  - OBJECTIVE: Preoperative anxiety influences the result of the treatment in
      patients. To assess preoperative anxiety the Amsterdam Preoperative Anxiety and
      Information Scale (APAIS) [1] was developed. The APAIS measures anxiety and the
      need-for-information with 6 items, with good reliability and validity. This
      article presents the first test of the German version of this screening
      instrument. METHODS: The German version of the APAIS was tested on 68 patients
      questioned before surgery on the lower extremities in the Orthopaedic Department
      of a University Hospital. From 68 patients, 47 (69%) were female and the average
      age was 55 years. Besides the APAIS, several additional questionnaires with
      similar or divergent content were administered for testing the convergent and
      discriminant validity of the APAIS (HADS, SCL-9-K, KASA, COSS, STOA). RESULTS:
      The two scales anxiety and need-for-information could be replicated by a factor
      analysis and had high reliability (anxiety: Cronbachs Alpha = 0.92; need-for
      information: Cronbachs Alpha = 0.86). As expected the scales of the APAIS
      correlated highly with different standard questionnaires which measure anxiety
      (KASA, STOA) and low with questionnaires of divergent contents (HADS depression,
      COSS). The APAIS-scales are independent of sex, age or previous surgeries.
      Patients with a higher need-for-information show higher anxiety (r=0.59) prior to
      surgery. CONCLUSIONS: During its first trial the German version of the APAIS
      proved to be a reliable and valid instrument. Furthermore, it is a good screening
      instrument to assess preoperative anxiety and need-for-information in clinical
      practice, especially due to its brevity. In further studies the predictive
      validity has to be examined in large heterogeneous samples.

PMID- 19742299
TI  - The assessment of mood at workplace - psychometric analyses of the revised
      Profile of Mood States (POMS) questionnaire.
AB  - With the Profile of Mood States (POMS), a German version of an international
      instrument for the assessment of mood is available. The paper introduces a new
      short version containing 24 items and four scales. In a study about indoor
      climate in 4596 office workers only a few missing values were noted. Psychometric
      analyses showed very good characteristics of the four scales regarding their
      internal consistency (Cronbach's alpha) and scale fit. High floor effects
      indicated a limited exhaustion of the scale range. Age and gender effects of the
      scale scores concerned the scales "vigour" and "fatigue". Furthermore, the scales
      of the POMS discriminated between groups with different self-reported disease
      incidences. A less beneficial characteristic of the POMS could be noted in terms
      of a high correlation of the scales "numbness" and "fatigue". With the tested
      version of the POMS, a short instrument with good psychometric properties has
      been presented which can be assessed in healthy as well as in health-impaired
      persons.

PMID- 19742301
TI  - Profile of central and effector memory T cells in the progression of chronic
      human chagas disease.
AB  - BACKGROUND: Chronic Chagas disease presents several different clinical
      manifestations ranging from asymptomatic to severe cardiac and/or digestive
      clinical forms. Several studies have demonstrated that immunoregulatory
      mechanisms are important processes for the control of the intense immune activity
      observed in the chronic phase. T cells play a critical role in parasite specific
      and non-specific immune response elicited by the host against Trypanosoma cruzi.
      Specifically, memory T cells, which are basically classified as central and
      effector memory cells, might have a distinct migratory activity, role and
      function during the human Chagas disease. METHODOLOGY/PRINCIPAL FINDINGS: Based
      on the hypothesis that the disease severity in humans is correlated to the
      quality of immune responses against T. cruzi, we evaluated the memory profile of
      peripheral CD4(+) and CD8(+) T lymphocytes as well as its cytokine secretion
      before and after in vitro antigenic stimulation. We evaluated cellular response
      from non-infected individuals (NI), patients with indeterminate (IND) or cardiac
      (CARD) clinical forms of Chagas disease. The expression of CD45RA, CD45RO and
      CCR7 surface molecules was determined on CD4(+) and CD8(+) T lymphocytes; the
      pattern of intracellular cytokines (IFN-gamma, IL-10) synthesized by naive and
      memory cells was determined by flow cytometry. Our results revealed that IND and
      CARD patients have relatively lower percentages of naive (CD45RA(high)) CD4(+)
      and CD8(+) T cells. However, statistical analysis of ex-vivo profiles of CD4(+) T
      cells showed that IND have lower percentage of CD45RA(high) in relation to non
      infected individuals, but not in relation to CARD. Elevated percentages of memory
      (CD45RO(high)) CD4(+) T cells were also demonstrated in infected individuals,
      although statistically significant differences were only observed between IND and
      NI groups. Furthermore, when we analyzed the profile of secreted cytokines, we
      observed that CARD patients presented a significantly higher percentage of
      CD8(+)CD45RA(high) IFN-gamma-producing cells in control cultures and after
      antigen pulsing with soluble epimastigote antigens. CONCLUSIONS: Based on a
      correlation between the frequency of IFN-gamma producing CD8+ T cells in the T
      cell memory compartment and the chronic chagasic myocarditis, we propose that
      memory T cells can be involved in the induction of the development of the severe
      clinical forms of the Chagas disease by mechanisms modulated by IFN-gamma.
      Furthermore, we showed that individuals from IND group presented more T(CM)
      CD4(+) T cells, which may induce a regulatory mechanism to protect the host
      against the exacerbated inflammatory response elicited by the infection.

PMID- 19742300
TI  - Islet endothelial activation and oxidative stress gene expression is reduced by
      IL-1Ra treatment in the type 2 diabetic GK rat.
AB  - BACKGROUND: Inflammation followed by fibrosis is a component of islet dysfunction
      in both rodent and human type 2 diabetes. Because islet inflammation may
      originate from endothelial cells, we assessed the expression of selected genes
      involved in endothelial cell activation in islets from a spontaneous model of
      type 2 diabetes, the Goto-Kakizaki (GK) rat. We also examined islet
      endotheliuml/oxidative stress (OS)/inflammation-related gene expression, islet
      vascularization and fibrosis after treatment with the interleukin-1 (IL-1)
      receptor antagonist (IL-1Ra). METHODOLOGY/PRINCIPAL FINDINGS: Gene expression was
      analyzed by quantitative RT-PCR on islets isolated from 10-week-old diabetic GK
      and control Wistar rats. Furthermore, GK rats were treated s.c twice daily with
      IL-1Ra (Kineret, Amgen, 100 mg/kg/day) or saline, from 4 weeks of age onwards
      (onset of diabetes). Four weeks later, islet gene analysis and pancreas
      immunochemistry were performed. Thirty-two genes were selected encoding molecules
      involved in endothelial cell activation, particularly fibrinolysis, vascular
      tone, OS, angiogenesis and also inflammation. All genes except those encoding
      angiotensinogen and epoxide hydrolase (that were decreased), and 12-lipoxygenase
      and vascular endothelial growth factor (that showed no change), were
      significantly up-regulated in GK islets. After IL-1Ra treatment of GK rats in
      vivo, most selected genes implied in endothelium/OS/immune cells/fibrosis were
      significantly down-regulated. IL-1Ra also improved islet vascularization, reduced
      fibrosis and ameliorated glycemia. CONCLUSIONS/SIGNIFICANCE: GK rat islets have
      increased mRNA expression of markers of early islet endothelial cell activation,
      possibly triggered by several metabolic factors, and also some defense
      mechanisms. The beneficial effect of IL-1Ra on most islet endothelial/OS/immune
      cells/fibrosis parameters analyzed highlights a major endothelial-related role
      for IL-1 in GK islet alterations. Thus, metabolically-altered islet endothelium
      might affect the beta-cell microenvironment and contribute to progressive type 2
      diabetic beta-cell dysfunction in GK rats. Counteracting islet endothelial cell
      inflammation might be one way to ameliorate/prevent beta-cell dysfunction in type
      2 diabetes.

PMID- 19742302
TI  - Use of cumulative incidence of novel influenza A/H1N1 in foreign travelers to
      estimate lower bounds on cumulative incidence in Mexico.
AB  - BACKGROUND: An accurate estimate of the total number of cases and severity of
      illness of an emerging infectious disease is required both to define the burden
      of the epidemic and to determine the severity of disease. When a novel pathogen
      first appears, affected individuals with severe symptoms are more likely to be
      diagnosed. Accordingly, the total number of cases will be underestimated and
      disease severity overestimated. This problem is manifest in the current epidemic
      of novel influenza A/H1N1. METHODS AND RESULTS: We used a simple approach to
      leverage measures of incident influenza A/H1N1 among a relatively small and well
      observed group of US, UK, Spanish and Canadian travelers who had visited Mexico
      to estimate the incidence among a much larger and less well surveyed population
      of Mexican residents. We estimate that a minimum of 113,000 to 375,000 cases of
      novel influenza A/H1N1 have occurred in Mexicans during the month of April, 2009.
      Such an estimate serves as a lower bound because it does not account for
      underreporting of cases in travelers or for nonrandom mixing between Mexican
      residents and visitors, which together could increase the estimates by more than
      an order of magnitude. CONCLUSIONS: We find that the number of cases in Mexican
      residents may exceed the number of confirmed cases by two to three orders of
      magnitude. While the extent of disease spread is greater than previously
      appreciated, our estimate suggests that severe disease is uncommon since the
      total number of cases is likely to be much larger than those of confirmed cases.

PMID- 19742303
TI  - Genetic ancestry, social classification, and racial inequalities in blood
      pressure in Southeastern Puerto Rico.
AB  - BACKGROUND: The role of race in human genetics and biomedical research is among
      the most contested issues in science. Much debate centers on the relative
      importance of genetic versus sociocultural factors in explaining racial
      inequalities in health. However, few studies integrate genetic and sociocultural
      data to test competing explanations directly. METHODOLOGY/PRINCIPAL FINDINGS: We
      draw on ethnographic, epidemiologic, and genetic data collected in Southeastern
      Puerto Rico to isolate two distinct variables for which race is often used as a
      proxy: genetic ancestry versus social classification. We show that color, an
      aspect of social classification based on the culturally defined meaning of race
      in Puerto Rico, better predicts blood pressure than does a genetic-based estimate
      of continental ancestry. We also find that incorporating sociocultural variables
      reveals a new and significant association between a candidate gene polymorphism
      for hypertension (alpha(2C) adrenergic receptor deletion) and blood pressure.
      CONCLUSIONS/SIGNIFICANCE: This study addresses the recognized need to measure
      both genetic and sociocultural factors in research on racial inequalities in
      health. Our preliminary results provide the most direct evidence to date that
      previously reported associations between genetic ancestry and health may be
      attributable to sociocultural factors related to race and racism, rather than to
      functional genetic differences between racially defined groups. Our results also
      imply that including sociocultural variables in future research may improve our
      ability to detect significant allele-phenotype associations. Thus, measuring
      sociocultural factors related to race may both empower future genetic association
      studies and help to clarify the biological consequences of social inequalities.

PMID- 19742304
TI  - The G-quadruplex ligand telomestatin impairs binding of topoisomerase IIIalpha to
      G-quadruplex-forming oligonucleotides and uncaps telomeres in ALT cells.
AB  - In Alternative Lengthening of Telomeres (ALT) cell lines, specific nuclear bodies
      called APBs (ALT-associated PML bodies) concentrate telomeric DNA, shelterin
      components and recombination factors associated with telomere recombination.
      Topoisomerase IIIalpha (Topo III) is an essential telomeric-associated factor in
      ALT cells. We show here that the binding of Topo III to telomeric G-overhang is
      modulated by G-quadruplex formation. Topo III binding to G-quadruplex-forming
      oligonucleotides was strongly inhibited by telomestatin, a potent and specific G
      quadruplex ligand. In ALT cells, telomestatin treatment resulted in the depletion
      of the Topo III/BLM/TRF2 complex and the disruption of APBs and led to the
      segregation of PML, shelterin components and Topo III. Interestingly, a DNA
      damage response was observed at telomeres in telomestatin-treated cells. These
      data indicate the importance of G-quadruplex stabilization during telomere
      maintenance in ALT cells. The function of TRF2/Topo III/BLM in the resolution of
      replication intermediates at telomeres is discussed.

PMID- 19742308
TI  - Synthetic Plasmodium-like hemozoin activates the immune response: a morphology -
      function study.
AB  - Increasing evidence points to an important role for hemozoin (HZ), the malaria
      pigment, in the immunopathology related to this infection. However, there is no
      consensus as to whether HZ exerts its immunostimulatory activity in absence of
      other parasite or host components. Contamination of native HZ preparations and
      the lack of a unified protocol to produce crystals that mimic those of Plasmodium
      HZ (PHZ) are major technical limitants when performing functional studies with
      HZ. In fact, the most commonly used methods generate a heterogeneous
      nanocrystalline material. Thus, it is likely that such aggregates do not resemble
      to PHZ and differ in their inflammatory properties. To address this issue, the
      present study was designed to establish whether synthetic HZ (sHZ) crystals
      produced by different methods vary in their morphology and in their ability to
      activate immune responses. We report a new method of HZ synthesis (the precise
      aqueous acid-catalyzed method) that yields homogeneous sHZ crystals (Plasmodium
      like HZ) which are very similar to PHZ in their size and physicochemical
      properties. Importantly, these crystals are devoid of protein and DNA
      contamination. Of interest, structure-function studies revealed that the size and
      shape of the synthetic crystals influences their ability to activate inflammatory
      responses (e.g. nitric oxide, chemokine and cytokine mRNA) in vitro and in vivo.
      In summary, our data confirm that sHZ possesses immunostimulatory properties and
      underline the importance of verifying by electron microscopy both the morphology
      and homogeneity of the synthetic crystals to ensure that they closely resemble
      those of the parasite. Periodic quality control experiments and unification of
      the method of HZ synthesis are key steps to unravel the role of HZ in malaria
      immunopathology.

PMID- 19742309
TI  - The non-canonical CTD of RNAP-II is essential for productive RNA synthesis in
      Trypanosoma brucei.
AB  - The carboxy-terminal domain (CTD) of the largest subunit (RPB1) of RNA polymerase
      II (RNAP-II) is essential for gene expression in metazoa and yeast. The canonical
      CTD is characterized by heptapeptide repeats. Differential phosphorylation of
      canonical CTD orchestrates transcriptional and co-transcriptional maturation of
      mRNA and snRNA. Many organisms, including trypanosomes, lack a canonical CTD. In
      these organisms, the CTD is called a non-canonical CTD or pseudo-CTD (PsiCTD. In
      the African trypanosome, Trypanosoma brucei, the PsiCTD is approximately 285
      amino acids long, rich in serines and prolines, and phosphorylated. We report
      that T. brucei RNAP-II lacking the entire PsiCTD or containing only a 95-amino
      acid-long PsiCTD failed to support cell viability. In contrast, RNAP-II with a
      186-amino-acid-long PsiCTD maintained cellular growth. RNAP-II with PsiCTD
      truncations resulted in abortive initiation of transcription. These data
      establish that non-canonical CTDs play an important role in gene expression.

PMID- 19742310
TI  - The complex spatio-temporal regulation of the Drosophila myoblast attractant gene
      duf/kirre.
AB  - A key early player in the regulation of myoblast fusion is the gene dumbfounded
      (duf, also known as kirre). Duf must be expressed, and function, in founder cells
      (FCs). A fixed number of FCs are chosen from a pool of equivalent myoblasts and
      serve to attract fusion-competent myoblasts (FCMs) to fuse with them to form a
      multinucleate muscle-fibre. The spatial and temporal regulation of duf expression
      and function are important and play a deciding role in choice of fibre number,
      location and perhaps size. We have used a combination of bioinformatics and
      functional enhancer deletion approaches to understand the regulation of duf. By
      transgenic enhancer-reporter deletion analysis of the duf regulatory region, we
      found that several distinct enhancer modules regulate duf expression in specific
      muscle founders of the embryo and the adult. In addition to existing
      bioinformatics tools, we used a new program for analysis of regulatory sequence,
      PhyloGibbs-MP, whose development was largely motivated by the requirements of
      this work. The results complement our deletion analysis by identifying
      transcription factors whose predicted binding regions match with our deletion
      constructs. Experimental evidence for the relevance of some of these TF binding
      sites comes from available ChIP-on-chip from the literature, and from our
      analysis of localization of myogenic transcription factors with duf enhancer
      reporter gene expression. Our results demonstrate the complex regulation in each
      founder cell of a gene that is expressed in all founder cells. They provide
      evidence for transcriptional control--both activation and repression--as an
      important player in the regulation of myoblast fusion. The set of enhancer
      constructs generated will be valuable in identifying novel trans-acting factor
      binding sites and chromatin regulation during myoblast fusion in Drosophila. Our
      results and the bioinformatics tools developed provide a basis for the study of
      the transcriptional regulation of other complex genes.

PMID- 19742311
TI  - Assessing risk in focal arboviral infections: are we missing the big or little
      picture?
AB  - BACKGROUND: Focal arboviral infections affecting a subset of the overall
      population present an often overlooked set of challenges in the assessment and
      reporting of risk and the detection of spatial patterns. Our objective was to
      assess the variation in risk when using different at-risk populations and
      geographic scales for the calculation of incidence risk and the detection of
      geographic hot-spots of infection. We explored these variations using a pediatric
      arbovirus, La Crosse virus (LACV), as our model. METHODS AND FINDINGS:
      Descriptive and cluster analyses were performed on probable and confirmed cases
      of LACV infections reported to the Tennessee Department of Health from 1997 to
      2006, using three at-risk populations (the total population, the population 18
      years and younger, and the population 15 years and younger) and at two geographic
      levels (county and census tract) to assess the variation in incidence risk and to
      investigate evidence of clustering using both global and local spatial
      statistics. We determined that the most appropriate at-risk population to
      calculate incidence risk and to assess the evidence of clustering was the
      population 15 years and younger. Based on our findings, the most appropriate
      geographical level to conduct spatial analyses and report incidence risk is the
      census tract level. The incidence risk in the population 15 years and younger at
      the county level ranged from 0 to 226.5 per 100,000 persons (median 41.5) in
      those counties reporting cases (n = 14) and at the census tract level it ranged
      from 50.9 to 673.9 per 100,000 persons (median 126.7) in those census tracts
      reporting cases (n = 51). To our knowledge, this is the highest reported
      incidence risk for this population at the county level for Tennessee and at the
      census tract level nationally. CONCLUSION: The results of this study indicate the
      possibility of missing disease clusters resulting from performing incidence risk
      investigations of focal diseases using inappropriate at-risk populations and/or
      at large geographic scales. Improved disease surveillance and health planning
      will result through the use of well defined at-risk populations and the use of
      appropriate geographic scales for the analysis and reporting of diseases. The
      finding of a high incidence risk of LACV infections in eastern Tennessee
      demonstrates that the vast majority of these infections continue to be under
      diagnosed and/or underreported in this region. Persistent prevention and
      surveillance efforts will be required to reduce exposure to infectious vectors
      and to detect new cases of infection in this region. Application of this study's
      observations in future investigations will enhance the quantification of
      incidence risk and the identification of high-risk groups within the population.

PMID- 19742312
TI  - Modeling the effects of integrating larval habitat source reduction and
      insecticide treated nets for malaria control.
AB  - Integrated vector management for malaria control has received a lot of recent
      interest. Attacking multiple points in the transmission cycle is hoped to act
      synergistically and improve upon current single-tool interventions based on the
      use of insecticide-treated bed nets (ITNs). In the present study, we
      theoretically examined the application of larval habitat source reduction with
      ITNs in reducing malaria transmission. We selected this type of environmental
      management to complement ITNs because of a potential secondary mode of action
      that both control strategies share. In addition to increasing vector mortality,
      ITNs reduce the rate at which female mosquitoes locate human hosts for blood
      feeding, thereby extending their gonotrophic cycle. Similarly, while reducing
      adult vector emergence and abundance, source reduction of larval habitats may
      prolong the cycle duration by extending delays in locating oviposition sites. We
      found, however, that source reduction of larval habitats only operates through
      this secondary mode of action when habitat density is below a critical threshold.
      Hence, we illustrate how this strategy becomes increasingly effective when larval
      habitats are limited. We also demonstrate that habitat source reduction is better
      suited to human populations of higher density and in the presence of insecticide
      resistance or when the insecticidal properties of ITNs are depleted.

PMID- 19742313
TI  - When right feels left: referral of touch and ownership between the hands.
AB  - Feeling touch on a body part is paradigmatically considered to require
      stimulation of tactile afferents from the body part in question, at least in
      healthy non-synaesthetic individuals. In contrast to this view, we report a
      perceptual illusion where people experience "phantom touches" on a right rubber
      hand when they see it brushed simultaneously with brushes applied to their left
      hand. Such illusory duplication and transfer of touch from the left to the right
      hand was only elicited when a homologous (i.e., left and right) pair of hands was
      brushed in synchrony for an extended period of time. This stimulation caused the
      majority of our participants to perceive the right rubber hand as their own and
      to sense two distinct touches--one located on the right rubber hand and the other
      on their left (stimulated) hand. This effect was supported by quantitative
      subjective reports in the form of questionnaires, behavioral data from a task in
      which participants pointed to the felt location of their right hand, and
      physiological evidence obtained by skin conductance responses when threatening
      the model hand. Our findings suggest that visual information augments
      subthreshold somatosensory responses in the ipsilateral hemisphere, thus
      producing a tactile experience from the non-stimulated body part. This finding is
      important because it reveals a new bilateral multisensory mechanism for tactile
      perception and limb ownership.

PMID- 19742314
TI  - ZNF93 increases resistance to ET-743 (Trabectedin; Yondelis) and PM00104
      (Zalypsis) in human cancer cell lines.
AB  - BACKGROUND: ET-743 (trabectedin, Yondelis) and PM00104 (Zalypsis) are marine
      derived compounds that have antitumor activity. ET-743 and PM00104 exposure over
      sustained periods of treatment will result in the development of drug resistance,
      but the mechanisms which lead to resistance are not yet understood.
      METHODOLOGY/PRINCIPAL FINDINGS: Human chondrosarcoma cell lines resistant to ET
      743 (CS-1/ER) or PM00104 (CS-1/PR) were established in this study. The CS-1/ER
      and CS-1/PR exhibited cross resistance to cisplatin and methotrexate but not to
      doxorubicin. Human Affymetrix Gene Chip arrays were used to examine relative gene
      expression in these cell lines. We found that a large number of genes have
      altered expression levels in CS-1/ER and CS-1/PR when compared to the parental
      cell line. 595 CS-1/ER and 498 CS-1/PR genes were identified as overexpressing;
      856 CS-1/ER and 874 CS-1/PR transcripts were identified as underexpressing. Three
      zinc finger protein (ZNF) genes were on the top 10 overexpressed genes list.
      These genes have not been previously associated with drug resistance in tumor
      cells. Differential expressions of ZNF93 and ZNF43 genes were confirmed in both
      CS-1/ER and CS-1/PR resistant cell lines by real-time RT-PCR. ZNF93 was
      overexpressed in two ET-743 resistant Ewing sarcoma cell lines as well as in a
      cisplatin resistant ovarian cancer cell line, but was not overexpressed in
      paclitaxel resistant cell lines. ZNF93 knockdown by siRNA in CS-1/ER and CS-1/PR
      caused increased sensitivity for ET-743, PM00104, and cisplatin. Furthermore,
      ZNF93 transfected CS-1 cells are relatively resistant to ET-743, PM00104 and
      cisplatin. CONCLUSIONS/SIGNIFICANCE: This study suggests that zinc finger
      proteins, and ZNF93 in particular, are involved in resistance to ET-743 and
      PM00104.

PMID- 19742315
TI  - Antiretroviral therapy initiation before, during, or after pregnancy in HIV-1
      infected women: maternal virologic, immunologic, and clinical response.
AB  - BACKGROUND: Pregnancy has been associated with a decreased risk of HIV disease
      progression in the highly active antiretroviral therapy (HAART) era. The effect
      of timing of HAART initiation relative to pregnancy on maternal virologic,
      immunologic and clinical outcomes has not been assessed. METHODS: We conducted a
      retrospective cohort study from 1997-2005 among 112 pregnant HIV-infected women
      who started HAART before (N = 12), during (N = 70) or after pregnancy (N = 30).
      RESULTS: Women initiating HAART before pregnancy had lower CD4+ nadir and higher
      baseline HIV-1 RNA. Women initiating HAART after pregnancy were more likely to
      receive triple-nucleoside reverse transcriptase inhibitors. Multivariable
      analyses adjusted for baseline CD4+ lymphocytes, baseline HIV-1 RNA, age, race,
      CD4+ lymphocyte count nadir, history of ADE, prior use of non-HAART ART, type of
      HAART regimen, prior pregnancies, and date of HAART start. In these models, women
      initiating HAART during pregnancy had better 6-month HIV-1 RNA and CD4+ changes
      than those initiating HAART after pregnancy (-0.35 vs. 0.10 log(10) copies/mL, P
      = 0.03 and 183.8 vs. -70.8 cells/mm(3), P = 0.03, respectively) but similar to
      those initiating HAART before pregnancy (-0.32 log(10) copies/mL, P = 0.96 and
      155.8 cells/mm(3), P = 0.81, respectively). There were 3 (25%) AIDS-defining
      events or deaths in women initiating HAART before pregnancy, 3 (4%) in those
      initiating HAART during pregnancy, and 5 (17%) in those initiating after
      pregnancy (P = 0.01). There were no statistical differences in rates of HIV
      disease progression between groups. CONCLUSIONS: HAART initiation during
      pregnancy was associated with better immunologic and virologic responses than
      initiation after pregnancy.

PMID- 19742316
TI  - LRP1 regulates architecture of the vascular wall by controlling PDGFRbeta
      dependent phosphatidylinositol 3-kinase activation.
AB  - BACKGROUND: Low density lipoprotein receptor-related protein 1 (LRP1) protects
      against atherosclerosis by regulating the activation of platelet-derived growth
      factor receptor beta (PDGFRbeta) in vascular smooth muscle cells (SMCs).
      Activated PDGFRbeta undergoes tyrosine phosphorylation and subsequently interacts
      with various signaling molecules, including phosphatidylinositol 3-kinase (PI3K),
      which binds to the phosphorylated tyrosine 739/750 residues in mice, and thus
      regulates actin polymerization and cell movement. METHODS AND PRINCIPAL FINDINGS:
      In this study, we found disorganized actin in the form of membrane ruffling and
      enhanced cell migration in LRP1-deficient (LRP1-/-) SMCs. Marfan syndrome-like
      phenotypes such as tortuous aortas, disrupted elastic layers and abnormally
      activated transforming growth factor beta (TGFbeta) signaling are present in
      smooth muscle-specific LRP1 knockout (smLRP1-/-) mice. To investigate the role of
      LRP1-regulated PI3K activation by PDGFRbeta in atherogenesis, we generated a
      strain of smLRP1-/- mice in which tyrosine 739/750 of the PDGFRbeta had been
      mutated to phenylalanines (PDGFRbeta F2/F2). Spontaneous atherosclerosis was
      significantly reduced in the absence of hypercholesterolemia in these mice
      compared to smLRP1-/- animals that express wild type PDGFR. Normal actin
      organization was restored and spontaneous SMC migration as well as PDGF-BB
      induced chemotaxis was dramatically reduced, despite continued overactivation of
      TGFbeta signaling, as indicated by high levels of nuclear phospho-Smad2.
      CONCLUSIONS AND SIGNIFICANCE: Our data suggest that LRP1 regulates actin
      organization and cell migration by controlling PDGFRbeta-dependent activation of
      PI3K. TGFbeta activation alone is not sufficient for the expression of the Marfan
      like vascular phenotype. Thus, regulation of PI3 Kinase by PDGFRbeta is essential
      for maintaining vascular integrity, and for the prevention of atherosclerosis as
      well as Marfan syndrome.

PMID- 19742317
TI  - AP-2alpha induces epigenetic silencing of tumor suppressive genes and
      microsatellite instability in head and neck squamous cell carcinoma.
AB  - BACKGROUND: Activator protein 2 alpha (AP-2alpha) is involved in a variety of
      physiological processes. Increased AP-2alpha expression correlates with
      progression in various squamous cell carcinomas, and a recent publication found
      AP-2alpha to be overexpressed in approximately 70% of Head and Neck Squamous Cell
      Carcinoma (HNSCC) patient samples. It was found to repress transcription of the
      tumor suppressor gene C/CAAT Enhancer Binding Protein alpha (C/EBPalpha), and its
      binding site correlated with upstream methylation of the C/EBPalpha promoter.
      Therefore, we investigated the potential for AP-2alpha to target methylation to
      additional genes that would be relevant to HNSCC pathogenesis. PRINCIPAL
      FINDINGS: Stable downregulation of AP-2alpha stable by shRNA in HNSCC cell lines
      correlated with decreased methylation of its target genes' regulatory regions.
      Furthermore, methylation of MLH1 in HNSCC with and without AP-2alpha
      downregulation revealed a correlation with microsatellite instability (MSI). ChIP
      analysis was used to confirm binding of AP-2alpha and HDAC1/2 to the targets. The
      effects of HDAC inhibition was assessed using Trichostatin A in a HNSCC cell
      line, which revealed that AP-2alpha targets methylation through HDAC recruitment.
      CONCLUSIONS: These findings are significant because they suggest AP-2alpha plays
      a role not only in epigenetic silencing, but also in genomic instability. This
      intensifies the potential level of regulation AP-2alpha has through
      transcriptional regulation. Furthermore, these findings have the potential to
      revolutionize the field of HNSCC therapy, and more generally the field of
      epigenetic therapy, by targeting a single gene that is involved in the malignant
      transformation via disrupting DNA repair and cell cycle control.

PMID- 19742318
TI  - Intestinal microbiota regulate xenobiotic metabolism in the liver.
AB  - BACKGROUND: The liver is the central organ for xenobiotic metabolism (XM) and is
      regulated by nuclear receptors such as CAR and PXR, which control the metabolism
      of drugs. Here we report that gut microbiota influences liver gene expression and
      alters xenobiotic metabolism in animals exposed to barbiturates. PRINCIPAL
      FINDINGS: By comparing hepatic gene expression on microarrays from germfree (GF)
      and conventionally-raised mice (SPF), we identified a cluster of 112
      differentially expressed target genes predominantly connected to xenobiotic
      metabolism and pathways inhibiting RXR function. These findings were functionally
      validated by exposing GF and SPF mice to pentobarbital which confirmed that
      xenobiotic metabolism in GF mice is significantly more efficient (shorter time of
      anesthesia) when compared to the SPF group. CONCLUSION: Our data demonstrate that
      gut microbiota modulates hepatic gene expression and function by altering its
      xenobiotic response to drugs without direct contact with the liver.

PMID- 19742319
TI  - Alpha-glucosidase promotes hemozoin formation in a blood-sucking bug: an
      evolutionary history.
AB  - BACKGROUND: Hematophagous insects digest large amounts of host hemoglobin and
      release heme inside their guts. In Rhodnius prolixus, hemoglobin-derived heme is
      detoxified by biomineralization, forming hemozoin (Hz). Recently, the involvement
      of the R. prolixus perimicrovillar membranes in Hz formation was demonstrated.
      METHODOLOGY/PRINCIPAL FINDINGS: Hz formation activity of an alpha-glucosidase was
      investigated. Hz formation was inhibited by specific alpha-glucosidase
      inhibitors. Moreover, Hz formation was sensitive to inhibition by
      Diethypyrocarbonate, suggesting a critical role of histidine residues in enzyme
      activity. Additionally, a polyclonal antibody raised against a phytophagous
      insect alpha-glucosidase was able to inhibit Hz formation. The alpha-glucosidase
      inhibitors have had no effects when used 10 h after the start of reaction,
      suggesting that alpha-glucosidase should act in the nucleation step of Hz
      formation. Hz formation was seen to be dependent on the substrate-binding site of
      enzyme, in a way that maltose, an enzyme substrate, blocks such activity. dsRNA,
      constructed using the sequence of alpha-glucosidase gene, was injected into R.
      prolixus females' hemocoel. Gene silencing was accomplished by reduction of both
      alpha-glucosidase and Hz formation activities. Insects were fed on plasma or
      hemin-enriched plasma and gene expression and activity of alpha-glucosidase were
      higher in the plasma plus hemin-fed insects. The deduced amino acid sequence of
      alpha-glucosidase shows a high similarity to the insect alpha-glucosidases, with
      critical histidine and aspartic residues conserved among the enzymes.
      CONCLUSIONS/SIGNIFICANCE: Herein the Hz formation is shown to be associated to an
      alpha-glucosidase, the biochemical marker from Hemipteran perimicrovillar
      membranes. Usually, these enzymes catalyze the hydrolysis of glycosidic bond. The
      results strongly suggest that alpha-glucosidase is responsible for Hz nucleation
      in the R. prolixus midgut, indicating that the plasticity of this enzyme may play
      an important role in conferring fitness to hemipteran hematophagy, for instance.

PMID- 19742320
TI  - A new mixed-backbone oligonucleotide against glucosylceramide synthase sensitizes
      multidrug-resistant tumors to apoptosis.
AB  - Enhanced ceramide glycosylation catalyzed by glucosylceramide synthase (GCS)
      limits therapeutic efficiencies of antineoplastic agents including doxorubicin in
      drug-resistant cancer cells. Aimed to determine the role of GCS in tumor response
      to chemotherapy, a new mixed-backbone oligonucleotide (MBO-asGCS) with higher
      stability and efficiency has been generated to silence human GCS gene. MBO-asGCS
      was taken up efficiently in both drug-sensitive and drug-resistant cells, but it
      selectively suppressed GCS overexpression, and sensitized drug-resistant cells.
      MBO-asGCS increased doxorubicin sensitivity by 83-fold in human NCI/ADR-RES, and
      43-fold in murine EMT6/AR1 breast cancer cells, respectively. In tumor-bearing
      mice, MBO-asGCS treatment dramatically inhibited the growth of multidrug
      resistant NCI/ADR-RE tumors, decreasing tumor volume to 37%, as compared with
      scrambled control. Furthermore, MBO-asGCS sensitized multidrug-resistant tumors
      to chemotherapy, increasing doxorubicin efficiency greater than 2-fold. The
      sensitization effects of MBO-asGCS relied on the decreases of gene expression and
      enzyme activity of GCS, and on the increases of C(18)-ceramide and of caspase
      executed apoptosis. MBO-asGCS was accumulation in tumor xenografts was greater in
      other tissues, excepting liver and kidneys; but MBO-asGCS did not exert
      significant toxic effects on liver and kidneys. This study, for the first time in
      vivo, has demonstrated that GCS is a promising therapeutic target for cancer drug
      resistance, and MBO-asGCS has the potential to be developed as an antineoplastic
      agent.

PMID- 19742321
TI  - Genetic variation in the proximal promoter of ABC and SLC superfamilies: liver
      and kidney specific expression and promoter activity predict variation.
AB  - Membrane transporters play crucial roles in the cellular uptake and efflux of an
      array of small molecules including nutrients, environmental toxins, and many
      clinically used drugs. We hypothesized that common genetic variation in the
      proximal promoter regions of transporter genes contribute to observed variation
      in drug response. A total of 579 polymorphisms were identified in the proximal
      promoters (-250 to +50 bp) and flanking 5' sequence of 107 transporters in the
      ATP Binding Cassette (ABC) and Solute Carrier (SLC) superfamilies in 272 DNA
      samples from ethnically diverse populations. Many transporter promoters contained
      multiple common polymorphisms. Using a sliding window analysis, we observed that,
      on average, nucleotide diversity (pi) was lowest at approximately 300 bp upstream
      of the transcription start site, suggesting that this region may harbor important
      functional elements. The proximal promoters of transporters that were highly
      expressed in the liver had greater nucleotide diversity than those that were
      highly expressed in the kidney consistent with greater negative selective
      pressure on the promoters of kidney transporters. Twenty-one promoters were
      evaluated for activity using reporter assays. Greater nucleotide diversity was
      observed in promoters with strong activity compared to promoters with weak
      activity, suggesting that weak promoters are under more negative selective
      pressure than promoters with high activity. Collectively, these results suggest
      that the proximal promoter region of membrane transporters is rich in variation
      and that variants in these regions may play a role in interindividual variation
      in drug disposition and response.

PMID- 19742322
TI  - Insulin gene expression is regulated by DNA methylation.
AB  - BACKGROUND: Insulin is a critical component of metabolic control, and as such,
      insulin gene expression has been the focus of extensive study. DNA sequences that
      regulate transcription of the insulin gene and the majority of regulatory factors
      have already been identified. However, only recently have other components of
      insulin gene expression been investigated, and in this study we examine the role
      of DNA methylation in the regulation of mouse and human insulin gene expression.
      METHODOLOGY/PRINCIPAL FINDINGS: Genomic DNA samples from several tissues were
      bisulfite-treated and sequenced which revealed that cytosine-guanosine
      dinucleotide (CpG) sites in both the mouse Ins2 and human INS promoters are
      uniquely demethylated in insulin-producing pancreatic beta cells. Methylation of
      these CpG sites suppressed insulin promoter-driven reporter gene activity by
      almost 90% and specific methylation of the CpG site in the cAMP responsive
      element (CRE) in the promoter alone suppressed insulin promoter activity by 50%.
      Methylation did not directly inhibit factor binding to the CRE in vitro, but
      inhibited ATF2 and CREB binding in vivo and conversely increased the binding of
      methyl CpG binding protein 2 (MeCP2). Examination of the Ins2 gene in mouse
      embryonic stem cell cultures revealed that it is fully methylated and becomes
      demethylated as the cells differentiate into insulin-expressing cells in vitro.
      CONCLUSIONS/SIGNIFICANCE: Our findings suggest that insulin promoter CpG
      demethylation may play a crucial role in beta cell maturation and tissue-specific
      insulin gene expression.

PMID- 19742323
TI  - Dimerization of tetherin is not essential for its antiviral activity against
      Lassa and Marburg viruses.
AB  - Tetherin (also known as BST2, CD317 or HM1.24) has recently been reported to
      inhibit a wide range of viruses. However, the antiviral mechanism of action of
      tetherin has not been determined. Both ends of the tetherin molecule are
      associated with the plasma membrane and it forms a homodimer. Therefore, a model
      in which progeny virions are retained on the cell surface by dimer formation
      between tetherin molecules on the viral envelope and plasma membrane has been
      proposed as the antiviral mechanism of action of this molecule. To investigate
      this possibility, we examined the correlation between dimerization and antiviral
      activity of tetherin in Lassa and Marburg virus-like particle production systems
      using tetherin mutants deficient in dimer formation. However, the tetherin mutant
      with complete loss of dimerization activity still showed apparent antiviral
      activity, indicating that dimerization of tetherin is not essential for its
      antiviral activity. This suggests that tetherin retains progeny virions on the
      cell surface by a mechanism other than dimerization.

PMID- 19742324
TI  - Nutrition controls mitochondrial biogenesis in the Drosophila adipose tissue
      through Delg and cyclin D/Cdk4.
AB  - MITOCHONDRIA ARE CELLULAR ORGANELLES THAT PERFORM CRITICAL METABOLIC FUNCTIONS:
      they generate energy from nutrients but also provide metabolites for de novo
      synthesis of fatty acids and several amino acids. Thus mitochondrial mass and
      activity must be coordinated with nutrient availability, yet this remains poorly
      understood. Here, we demonstrate that Drosophila larvae grown in low yeast food
      have strong defects in mitochondrial abundance and respiration activity in the
      larval fat body. This correlates with reduced expression of genes encoding
      mitochondrial proteins, particularly genes involved in oxidative phosphorylation.
      Second, genes involved in glutamine metabolism are also expressed in a nutrient
      dependent manner, suggesting a coordination of amino acid synthesis with
      mitochondrial abundance and activity. Moreover, we show that Delg (CG6338), the
      Drosophila homologue to the alpha subunit of mammalian transcription factor NRF
      2/GABP, is required for proper expression of most genes encoding mitochondrial
      proteins. Our data demonstrate that Delg is critical to adjust mitochondrial
      abundance in respect to Cyclin D/Cdk4, a growth-promoting complex and glutamine
      metabolism according to nutrient availability. However, in contrast to nutrients,
      Delg is not involved in the regulation of mitochondrial activity in the fat body.
      These findings are the first genetic evidence that the regulation of
      mitochondrial mass can be uncoupled from mitochondrial activity.

PMID- 19742325
TI  - The survey of H5N1 flu virus in wild birds in 14 Provinces of China from 2004 to
      2007.
AB  - BACKGROUND: The highly pathogenic H5N1 avian influenza emerged in the year 1996
      in Asia, and has spread to Europe and Africa recently. At present, effective
      monitoring and data analysis of H5N1 are not sufficient in Chinese mainland.
      METHODOLOGY/PRINCIPAL FINDINGS: During the period from April of 2004 to August of
      2007, we collected 14,472 wild bird samples covering 56 species of 10 orders in
      14 provinces of China and monitored the prevalence of flu virus based on RT-PCR
      specific for H5N1 subtype. The 149 positive samples involved six orders.
      Anseriformes had the highest prevalence while Passeriformes had the lowest
      prevalence (2.70% versus 0.36%). Among the 24 positive species, mallard (Anas
      platyrhynchos) had the highest prevalence (4.37%). A difference of prevalence was
      found among 14 provinces. Qinghai had a higher prevalence than the other 13
      provinces combined (3.88% versus 0.43%). The prevalence in three species in
      Qinghai province (Pintail (Anas acuta), Mallard (Anas platyrhynchos) and Tufted
      Duck (Aythya fuligula)) were obviously higher than those in other 13 provinces.
      The results of sequence analysis indicated that the 17 strains isolated from wild
      birds were distributed in five clades (2.3.1, 2.2, 2.5, 6, and 7), which
      suggested that genetic diversity existed among H5N1 viruses isolated from wild
      birds. The five isolates from Qinghai came from one clade (2.2) and had a short
      evolutionary distance with the isolates obtained from Qinghai in the year 2005.
      CONCLUSIONS/SIGNIFICANCE: We have measured the prevalence of H5N1 virus in 56
      species of wild birds in 14 provinces of China. Continuous monitoring in the
      field should be carried out to know whether H5N1 virus can be maintained by wild
      birds.

PMID- 19742326
TI  - Repression of RNA polymerase II elongation in vivo is critically dependent on the
      C-terminus of Spt5.
AB  - The stalling of RNA polymerase II (RNAPII) at the promoters of many genes,
      including developmental regulators, stress-responsive genes, and HIVLTR, suggests
      transcription elongation as a critical regulatory step in addition to initiation.
      Spt5, the large subunit of the DRB sensitivity-inducing factor (DSIF), represses
      or activates RNAPII elongation in vitro. How RNAPII elongation is repressed in
      vivo is not well understood. Here we report that CTR1 and CTR2CT, the two repeat
      containing regions constituting the C-terminus of Spt5, play a redundant role in
      repressing RNAPII elongation in vivo. First, mis-expression of Spt5 lacking CTR1
      or CTR2CT is inconsequential, but mis-expression of Spt5 lacking the entire C
      terminus (termed NSpt5) dominantly impairs embryogenesis in zebrafish. Second,
      NSpt5 de-represses the transcription of hsp70-4 in zebrafish embryos and HIVLTR
      in cultured human cells, which are repressed at the RNAPII elongation step under
      non-inducible conditions. Third, NSpt5 directly associates with hsp70-4 chromatin
      in vivo and increases the occupancy of RNAPII, positive transcription elongation
      factor b (P-TEFb), histone H3 Lys 4 trimethylation (H3K4Me3), and surprisingly,
      the negative elongation factor A (NELF-A) at the locus, indicating a direct
      action of NSpt5 on the elongation repressed locus. Together, these results reveal
      a dominant activity of NSpt5 to de-repress RNAPII elongation, and suggest that
      the C-terminus of Spt5 is critical for repressing RNAPII elongation in vivo.

PMID- 19742327
TI  - Fluorescence-based monitoring of in vivo neural activity using a circuit-tracing
      pseudorabies virus.
AB  - The study of coordinated activity in neuronal circuits has been challenging
      without a method to simultaneously report activity and connectivity. Here we
      present the first use of pseudorabies virus (PRV), which spreads through
      synaptically connected neurons, to express a fluorescent calcium indicator
      protein and monitor neuronal activity in a living animal. Fluorescence signals
      were proportional to action potential number and could reliably detect single
      action potentials in vitro. With two-photon imaging in vivo, we observed both
      spontaneous and stimulated activity in neurons of infected murine peripheral
      autonomic submandibular ganglia (SMG). We optically recorded the SMG response in
      the salivary circuit to direct electrical stimulation of the presynaptic axons
      and to physiologically relevant sensory stimulation of the oral cavity. During a
      time window of 48 hours after inoculation, few spontaneous transients occurred.
      By 72 hours, we identified more frequent and prolonged spontaneous calcium
      transients, suggestive of neuronal or tissue responses to infection that
      influence calcium signaling. Our work establishes in vivo investigation of
      physiological neuronal circuit activity and subsequent effects of infection with
      single cell resolution.

PMID- 19742331
TI  - [Stress gastrointestinal bleeding in critically ill patients and its effect on
      the prognosis].
AB  - OBJECTIVE: To investigate stress gastrointestinal bleeding in critically ill
      patients and its effect on the prognosis. METHODS: Clinical data of 1148
      critically ill patients consecutively admitted to Intensive Care Unit of East
      Campuses of Peking Union Medical College Hospital during 2008 were analyzed
      retrospectively. The main contents of investigation included morbility and
      mortality of stress gastrointestinal bleeding in critically ill patients and its
      relationship with multiple organ dysfunction. RESULTS: Among the 1148 critically
      ill patients, organ dysfunction occurred in 254 cases, including 57 cases with
      shock, 124 with respiratory dysfunction, 46 with acute renal dysfunction, 192
      with coagulation dysfunction and 40 with stress gastrointestinal bleeding. The
      patients with stress gastrointestinal bleeding took up 15.7% among organ
      dysfunction patients and 3.5% among critically ill patients. 97.5% stress
      gastrointestinal bleeding accompanied with other organ dysfunction. The mortality
      of stress gastrointestinal bleeding was 40.0%, which was higher than that of
      shock (28.1%), respiratory dysfunction (22.6%), renal dysfunction (30.4%) and
      coagulation dysfunction (13.5%) (all P<0.05). Binary Logistic regression analysis
      found that stress gastrointestinal bleeding was an independent risk factor
      associated with mortality (P<0.05). CONCLUSION: The patients with stress
      gastrointestinal bleeding usually have a poor prognosis.

PMID- 19742332
TI  - [Evaluation of the gastrointestinal decompression after gastrectomy: a
      prospective randomized controlled trial].
AB  - OBJECTIVE: To evaluate the value of using nasogastric tube for patients after
      gastrectomy. METHODS: One hundred and eight patients undergone gastrectomy were
      divided randomizely into nasogastric decompression group(n=53) and non
      nasogastric decompression group (n=55). Gastrointestinal function and
      postoperative complications were compared between the two groups. RESULTS:
      Between nasogastric decompression group and non-nasogastric decompression group,
      no significant differences in postoperative complications (20.8% vs 23.6%,
      P=0.719), postoperative time of flatus [(3.2+/-0.9) d vs (3.0+/-0.7) d, P=0.192],
      recovery time of drinking [(5.9+/-3.4) d vs (5.1+/-1.6) d, P=0.143], eating time
      of fluid food [(7.8+/-3.6) d vs (6.8+/-1.8) d, P=0.085] and eating time of semi
      fluid food [(9.8+/-3.5) d vs (8.8+/-1.9) d, P=0.081] were found. While the
      recovery time of bowl sound [(1.8+/-0.7) d vs (2.2+/-0.9) d, (P=0.013)] and
      hospital stay [(10.2+/-2.1) d vs (11.7+/-4.3) d, (P=0.021)] were shorter in non
      nasogastric decompression group. CONCLUSION: It is not necessary to use
      nasogastric decompression for patients after gastrectomy.

PMID- 19742330
TI  - Treatment outcomes of multidrug-resistant tuberculosis: a systematic review and
      meta-analysis.
AB  - BACKGROUND: Treatment outcomes for multidrug-resistant Mycobacterium Tuberculosis
      (MDRTB) are generally poor compared to drug sensitive disease. We sought to
      estimate treatment outcomes and identify risk factors associated with poor
      outcomes in patients with MDRTB. METHODOLOGY/PRINCIPAL FINDINGS: We performed a
      systematic search (to December 2008) to identify trials describing outcomes of
      patients treated for MDRTB. We pooled appropriate data to estimate WHO-defined
      outcomes at the end of treatment and follow-up. Where appropriate, pooled
      covariates were analyzed to identify factors associated with worse outcomes.
      Among articles identified, 36 met our inclusion criteria, representing 31
      treatment programmes from 21 countries. In a pooled analysis, 62% [95% CI 57-67]
      of patients had successful outcomes, while 13% [9]-[17] defaulted, 11% [9]-[13]
      died, and 2% [1]-[4] were transferred out. Factors associated with worse outcome
      included male gender 0.61 (OR for successful outcome) [0.46-0.82], alcohol abuse
      0.49 [0.39-0.63], low BMI 0.41[0.23-0.72], smear positivity at diagnosis 0.53
      [0.31-0.91], fluoroquinolone resistance 0.45 [0.22-0.91] and the presence of an
      XDR resistance pattern 0.57 [0.41-0.80]. Factors associated with successful
      outcome were surgical intervention 1.91 [1.44-2.53], no previous treatment 1.42
      [1.05-1.94], and fluoroquinolone use 2.20 [1.19-4.09]. CONCLUSIONS/SIGNIFICANCE:
      We have identified several factors associated with poor outcomes where
      interventions may be targeted. In addition, we have identified high rates of
      default, which likely contributes to the development and spread of MDRTB.

PMID- 19742333
TI  - [Efficacy and safety of abdominal drainage after gastrectomy for gastric cancer
      patients: a systematic review].
AB  - OBJECTIVE: To assess the efficacy and safety of gastrectomy abdominal drainage
      after gastrectomy in gastric cancer patients. METHODS: Cochrane systematic
      evaluation was used to search through Cochrane library (2007-No.3) of clinical
      comparative trail, PubMed (1976-2008), Embase (1982-2008), Chinese Biomedical
      Literature Database (CBM 1979-2008), Chinese Scientific Journal Full-text
      Database (CSJD 1989-2008) and Chinese Journal Full-text Database (CJFD1994-2008),
      aided with manual retrieval and other retrievals. The quality of the assessment
      was independently evaluated and cross-checked by two evaluators. The results of
      homogeneous studies were analyzed with RevMan4.2.10 software. RESULTS: A total of
      47 articles were retrieved. Three randomized controlled trials were involved. A
      total of 338 patients were studied. Of the 338 patients, 160 were treated with
      total gastrectomy, 178 subtotal gastrectomy. Among the 338 patients, 167 were
      treated without abdominal drainage. Above 3 trials did not report blind method
      and did not describe method of allocation concealment. No significant differences
      were found in pulmonary complication, wound infection, intra-abdominal abscess,
      clinical leakage and initiation of soft diet between abdominal drainage group and
      without abdominal drainage group. Statistical results showed odds ratio
      (OR)=1.23, 95% CI=0.49-3.07 for pulmonary complication; OR=1.09, 95% CI=0.36-3.29
      for wound infection; OR=1.28, 95% CI=0.28-5.8 for intra-abdominal abscess;
      OR=1.53, 95% CI=0.25-9.42 for anastomotic leakage; OR=1.78, 95% CI=0.37-8.56 for
      hospital mortality; WMD=0.12, 95% CI=-0.11-0.35 for initiation of soft diet.
      Besides, significant difference was found in hospital stay (WMD=0.65, 95% CI=0.03
      1.26), and abdominal drainage group was longer. CONCLUSION: Abdominal drainage
      after gastrectomy should not be recommended as a regular treatment for gastric
      cancer patients.

PMID- 19742334
TI  - [Observation of fast track surgery in patients with gastric cancer].
AB  - OBJECTIVE: To investigate the effects of fast track surgery on patients with
      gastric cancer in perioperative period. METHODS: Ninety-two patients with gastric
      cancer undergone radical operations were randomly divided into two groups: fast
      track group (n=46, fast track surgery) and control group(n=46, traditional
      surgery). Serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6
      (IL-6) and C reaction protein (CRP) in the 92 patients were assayed
      preoperatively and at day 1, 3, 7 postoperatively, and the resting energy
      expenditure (REE) was also measured by indirect calorimetry in the morning. The
      postoperative hospital stay, duration of fever, medical cost, postoperative time
      of flatus and postoperative complications were recorded and compared
      respectively. RESULTS: At postoperative day 1 and 3, serum levels of TNF-alpha
      were (12.67+/-2.68) fmmol/L and (13.19+/-2.75) fmmol/L in fast track group,
      (14.74+/-3.18) fmmol/L and (15.56+/-2.99) fmmol/L in control group; serum levels
      of IL-6 were (112.52+/-24.73) ng/L and (129.03+/-22.75) ng/L in fast track group,
      (123.90+/-22.52) ng/L and (142.67+/-20.33) ng/L in control group. The levels of
      IL-6 and TNF-alpha in fast track group were significantly lower than those in
      control group (all P<0.05). At postoperative day 1, 3 and 7, serum levels of CRP
      in fast track group were significantly lower than those in control group
      [d1(56.20+/-11.47) g/L vs (71.07+/-17.32) g/L, d3(136.09+/-19.78) g/L vs
      (157.78+/-28.18) g/L, d7 (48.53+/-12.95) g/L vs (64.72+/-19.73) g/L] (all
      P<0.05). At postoperative day 1 and day 3, the REE in fast track group were
      significantly lower those than in control group [d1(5713.96+/-619.44) kJ/d vs
      (6176.04+/-614.46) kJ/d, d3 (5298.49+/-639.36) kJ/d vs (5627.94+/-656.72) kJ/d]
      (all P<0.05). The postoperative duration of fever [2(2.0-3.0) d vs 4(2.8-4.0) d],
      postoperative time of flatus [3(2.0-4.0) d vs 4(3.8-5.0) d], postoperative
      hospital stay [6(6.0-7.0) d vs 8(7.0-8.3) d] and treatment expense [(27 201+/
      3857) Chinese yuan vs (31 006+/-3555) Chinese yuan] in fast track group were also
      significantly lower than those in control group (P<0.01). There were no
      significant differences in complications between the two groups(P>0.05). The
      quality of life score on discharge in fast track group was significantly higher
      than that in control group (15.74+/-1.82 vs 14.67+/-1.27, P<0.01). CONCLUSION:
      Fast track surgery can ameliorate stress reaction, decrease postoperative
      patients' REE during perioperative period and accelerate the rehabilitation of
      patients with gastric cancer.

PMID- 19742335
TI  - [Resection of pancreatic capsule and anterior layer of transverse mesocolon in
      radical gastrectomy and its clinical significance].
AB  - OBJECTIVE: To investigate the clinical significance of resection of the
      pancreatic capsule and anterior layer of transverse mesocolon in radical
      gastrectomy. METHODS: Between January 2007 and July 2008, a total of 213 gastric
      cancer patients enrolled in the study. These patients were randomly assigned into
      two groups: 105 in group R and 108 in group N. Only in group R were the
      pancreatic capsule and anterior layer of transverse mesocolon resected during
      radical gastrectomy. The pancreatic capsule and anterior layer of transverse
      mesocolon were histologically analyzed for metastasis. The data including blood
      loss during operations, number of dissected lymph nodes and postoperative
      complications were analyzed in both groups. RESULTS: There were no significant
      differences between the two groups in blood loss during operation and
      postoperative complications, but the differences in operation time and number of
      dissected lymph nodes between the two groups were significant. Metastases to the
      pancreatic capsule and/or anterior layer of transverse mesocolon were diagnosed
      in nine (8.6%) patients of group R. The metastases to the pancreatic capsule
      and/or anterior layer of transverse mesocolon were found to be associated with
      tumor invasion depth, anterior or posterior gastric wall, clinical staging and
      perigastric lymph node metastasis extent (P<0.05), but not with age, gender,
      tumor location, size, Borrmann type and pathological classification (P>0.05).
      CONCLUSIONS: Resection of pancreatic capsule and anterior layer of transverse
      mesocolon in group R does not increase postoperative complications in comparison
      with group N. The resection is beneficial to the patients with advanced gastric
      cancer staging relatively late because of potential metastasis to pancreatic
      capsule and anterior layer of transverse mesocolon.

PMID- 19742336
TI  - [Efficacy and prognostic analysis on surgical resection of pulmonary metastasis
      from colorectal cancer].
AB  - OBJECTIVE: To elucidate the efficacy and probable prognostic factors of surgical
      resection of pulmonary metastasis from colorectal cancer. METHODS: Clinical data
      and outcomes of 35 colorectal patients with pulmonary metastasis undergone
      pulmonary metastasectomy were analyzed retrospectively. RESULTS: Median follow-up
      time was 48.0 months. The median overall survival time was 36.0 months. Five-year
      survival rate was 33.0%. Nineteen patients died of tumor progression. Sixteen
      patients were survival including survival with tumor (10 cases) and without tumor
      (6 cases). One patient was still alive without tumor for 164 months. Univariate
      analysis revealed that disease free interval (DFI) was a prognostic risk factor,
      while gender, age, primary tumor site, pulmonary metastasis size and location,
      surgical procedure, pre-surgical CEA level, re-metastasectomy did not show
      influence on the survival time after pulmonary metastasectomy. CONCLUSIONS: For
      some selected patients with indication, pulmonary metastasectomy may be a
      potential curative method. DFI may be associated with the prognosis after
      pulmonary metastasectomy.

PMID- 19742337
TI  - [Preliminary report about the screening program for colorectal cancer by
      sequential fecal occult blood in Wuhan area for 4 years].
AB  - OBJECTIVE: To evaluate the sequential fecal occult blood test (SFOBT) program for
      the screening of colorectal cancer and elucidate the prevalence of colorectal
      cancer in Wuhan area. METHODS: At 19 screening sites, 63,961 residents were
      recruited as target population according to random cluster and stratified
      sampling for four years (between 2005 and 2008). Residents aged over 40 years old
      received SFOBT. Those with positive SFOBT underwent colonoscopy. RESULTS: The
      target population was 63,961. There were 25,837 people whose age was over 40.
      Finally, 7784 participants received the SFOBT screening, with a medium age of 56
      years old. The positive rate of SFOBT was 12.3% (956 persons). Of the 956
      persons, 240 participants underwent colonoscopy. Colorectal cancer was found in
      14 cases (6.5%), gastric cancer in 2 cases (0.9%), colorectal adenoma in 53
      cases(24.8%), colorectal inflammation in 80 cases (37.3%) and hemorrhoids in 65
      cases (30.4%). CONCLUSIONS: The prevalence of colorectal cancer is relatively
      high in Wuhan area. The SFOBT is available and feasible in screening early
      changes of colorectal cancer.

PMID- 19742338
TI  - [Transsacral resection for presacral tumors].
AB  - OBJECTIVE: To explore the operation indication and safety of presacral tumor.
      METHODS: Clinical data of 36 patients with presacral tumor from November 1990 to
      May 2006 treated in our hospital, in whom 23 patients underwent trans-sacral
      operation, were analyzed retrospectively. RESULTS: The operation time was from 43
      to 210 min (average 94 min). The volume of blood loss was from 30 to 2000 ml
      (average 350 ml). Hospital stay was from 8 to 16 days (average 10.7 days). There
      were 13 different pathology types of tumors in the 36 patients including 26.4% of
      malignancy. Complications of trans-sacral operation included 1 case of ureteral
      damage, 1 case of sacral wound hernia, 1 case of presacral abscess who was healed
      by sigmoid stoma and wound drainage. CONCLUSION: Trans-sacral resection of low
      presacral tumor is safe and effective with less trauma, less bleeding and quick
      recovery.

PMID- 19742339
TI  - [Application of GORE-TEX Dual Mesh fixing into peritoneum in sigmoid-colostomy to
      prevent peristomal hernia].
AB  - OBJECTIVE: To investigate the effect of GORE-TEX Dual Mesh fixing into peritoneum
      in sigmoid-colostomy on the prevention of peristomal hernia. METHODS: Sixty
      patients undergone sigmoid-colostomy from Jan. 2003 to Jan. 2005 in the first
      affiliated hospital of Sun Yat-sen University were selected and randomly divided
      into two groups. Patients received papillary sigmoid-colostomy through rectus
      abdominis and peritoneum in control group and GORE-TEX Dual Mesh fixing into
      peritoneum during sigmoid-colostomy in observation group. Complications and
      recurrence rate were recorded in follow-up period. RESULTS: Peristomal hernia
      occurred in eight patients (8/30) in control group (26.7%), while no hernia
      happened in observation group (0/30). CONCLUSION: GORE-TEX Dual Mesh fixing into
      peritoneum in sigmoid-colostomy can prevent peristomal hernia.

PMID- 19742340
TI  - [Analysis of risk factors affecting operative outcome of small bowel
      obstruction].
AB  - OBJECTIVE: To evaluate the risk factors affecting the early postoperative
      outcomes in patients with small bowel obstruction. METHODS: Clinical data of 193
      patients with small bowel obstruction undergone operation were analyzed
      retrospectively. A range of factors were investigated to estimate postoperative
      outcome, including gender, age, comorbidities, etiology of obstruction, presence
      of strangulated bowel (viable or nonviable), leukocyte count, temperature, and
      heart rate. Logistic regression analysis was used to study the prognostic value
      of each significant variable in terms of postoperation. RESULTS: The major causes
      of small bowel obstruction were adhesion and hernia, contributing 38.9% and 37.8%
      of all cases, respectively. Strangulation occurred in 42.0% and caused nonviable
      bowel in 23.3% of obstructing episodes. Elderly (>or=70 years), diabetes,
      malignant tumors WBC >15x10(9)/L were independent significant factors associated
      with bowel strangulation. The overall complication rate was 16.1%, the 30-day
      mortality was 4.1%, and the median postoperative hospital stay was 13 days. Age
      >or=70 years and bowel resection were significantly associated with postoperative
      complications in the univariate analysis. Only elderly and malignant obstruction
      were significantly associated with operative mortality in multivariate logistic
      regression. CONCLUSIONS: Surgery for small bowel obstruction is still associated
      with significant mortality and morbidity. Elderly is significantly associated
      with an increased incidence of strangulation, operative mortality, and
      complications.

PMID- 19742341
TI  - [Clinical features of colorectal mucinous adenocarcinoma].
AB  - OBJECTIVE: To investigate the clinicopathological characteristics and prognosis
      of colorectal mucinous adenocarcinoma (MAC) and non-mucinous adenocarcinoma
      (NMAC). METHODS: Clinical data of 2089 cases with colorectal cancer from 1994 to
      2007 in our hospital, including 169 patients diagnosed as mucinous adenocarcinoma
      were analyzed retrospectively. RESULTS: As compared to NMAC, the tumor diameter
      of MAC was longer[(5.52+/-3.56) cm vs (4.62+/-2.68) cm, P<0.01]; the age of MAC
      was younger [(52.3+/-16.5) vs (58.7+/-13.6) years, P<0.01]. The rates of tumor
      location in colon (97 cases,57.4% vs 814 cases, 44.3%, in MAC and NMAC) were
      significantly different (P<0.01). Compared with NMAC, MAC had more lymph node
      involvement (103 cases, 60.9% vs 929 cases, 50.1%), more often in serosa
      infiltration (116 cases, 68.7% vs 914 cases, 49.8%), more peritoneal
      dissemination (26 cases, 15.4% vs 125 cases, 6.8%), and adjacent organ invasion
      (44 cases, 26.0% vs 300 cases, 16.3%) (P<0.01). The rate of radical resection
      (86.4% vs 91.5%), hepatic metastasis (5.3% vs 8.5%) and local recurrence had no
      significant difference between patients with mucinous and non-mucinous
      adenocarcinoma (P>0.05). In comparison to NMAC patients, MAC patients were worse
      in long-term overall survival, the survival of receiving radical resection and of
      TNM stage (II+III) group (P<0.01). Survivals were not significantly different in
      TNM stage I and IV groups between mucinous and non-mucinous adenocarcinoma
      (P>0.05). CONCLUSIONS: Colorectal mucinous adenocarcinoma patients have worse
      outcome in comparison to non-mucinous adenocarcinoma patients. Mucinous
      adenocarcinoma may have special biological behavior, which is an independent
      prognostic factor for patients with colorectal cancer.

PMID- 19742342
TI  - [Maintenance effect of polyglycosides of Tripterygium wilfordii on remission in
      postoperative Crohn disease].
AB  - OBJECTIVE: To observe the maintenance effect of polyglycosides of Tripterygium
      wilfordii (GTW) on remission in postoperative Crohn disease (CD). METHODS: From
      2005 to 2007, 45 adult cases of postoperative Crohn disease were randomly divided
      into two groups, GTW group and mesalazine group, which received GTW and
      mesalazine treatment respectively. CD activity index (CDAI) and clinical markers
      were collected at 0, 3, 6, 12 months or at the onset of symptoms. Ileocolonoscopy
      was performed at the end of the trial (1 year after operation) or at the onset of
      symptoms, and recurrence score were recorded. RESULTS: No clinical recurrence was
      ascertained in both groups at 3 months. Four patients (18.2%) in GTW group
      relapsed and 5 (21.7%) in mesalazine group relapsed at 6 months (P=0.530). Seven
      patients (31.8%) in GTW group and 9 (39.1%) in mesalazine group relapsed at one
      year (P=0.421). Ten patients (45.5%) in GTW group had endoscopic recurrence
      compared with 14 (60.9%) in mesalazine group at one year(P=0.231). There were no
      significant differences between two groups. CONCLUSION: GTW is similar to
      mesalazine in maintenance of remission of postoperative Crohn disease.

PMID- 19742343
TI  - [Effects of 5-Aza-2'-deoxycytidine and trichostatin A on P16, hMLH1 and MGMT
      genes and DNA methylation in human gastric cancer cells].
AB  - OBJECTIVE: To investigate the effects of 5-Aza-2'-deoxycytidine (5-Aza-dC) and
      trichostatin A (TSA) on DNA methylation and expression of P16, hMLH1 and MGMT
      genes in the human gastric cancer cell line MGC-803, and to explore the mechanism
      of P16, hMLH1 and MGMT gene silencing in human gastric cancer cells. METHODS: MGC
      803 cells were cultured in RPMI-1640 medium and were treated with 5-Aza-dC or
      TSA. Methylation-specific polymerase chain reaction (MS-PCR) was used to detect
      the promoter methylation status of P16, hMLH1 and MGMT genes. RT-PCR was used to
      detect the mRNA expressions of P16, hMLH1 and MGMT. RESULTS: Promoter
      hypermethylation of P16, hMLH1 and MGMT genes were detected in MGC-803 cells, and
      mRNA expressions of P16, hMLH1 and MGMT were absent before treatment. After
      treatment with 5-Aza-dC, the promoter region of the P16, hMLH1 and MGMT gene
      exhibited a demethylation status, and their mRNA expressions were increased. The
      treatment with TSA had no effects on DNA demethylation or restoration of P16 or
      hMLH1 expression. P16, hMLH1 and MGMT mRNA relative expression levels after
      treatment with a combination of 5-Aza-dC and TSA were 0.412+/-0.030, 0.397+/
      0.024 and 0.553+/-0.043 respectively, which were higher than those after 5-Aza-dC
      treatment alone (0.221+/-0.022, 0.214+/-0.018 and 0.156+/-0.017, all P<0.05).
      CONCLUSIONS: Promoter hypermethylation is a major mechanism of P16, hMLH1 and
      MGMT gene silencing in human gastric cancer cells. Treatment with 5-Aza-dC alone
      or the combination of 5-Aza-dC and TSA can reactivate the expressions of these
      genes.

PMID- 19742344
TI  - [Relationship between the expression of hypoxia-inducible factor-1alpha and
      chemotherapy response in gastric carcinoma].
AB  - OBJECTIVE: To evaluate the relationship of hypoxia-inducible factor (HIF)-1alpha
      expression with chemotherapy response in gastric cancer and its clinical outcome.
      METHODS: Leucovorin (CF) and 5-fluorouracil (5-FU) in combination with
      oxaliplatin (L-OHP) were used in 52 patients with gastric carcinoma (GC) at
      advanced stage. CF 200 mg/m(2) was intravenous drop for 2 h at day 1 and day 14.
      5-FU 1500 mg/m(2) was continuously intravenous drop for 46 h at day 1 and day 14.
      L-OHP 85 mg/m(2) was intravenous drop for 2 h at day 1 and day 14. Four-week was
      one cycle. All the patients received 4 cycles of chemotherapy at least.
      Chemotherapy response and clinical outcome were evaluated. Immunohistochemistry
      was used to examine the protein expressions of HIF-1alpha, P-gp and MRP4 by
      tissue microarray in GC. Twenty-seven normal gastric tissue samples were used as
      control group. RESULTS: The positive expression rates of HIF-lalpha, P-gp and
      MRP4 in tumor samples were 53.9%, 51.9% and 57.7% respectively, which were
      significantly higher than those in normal gastric tissues (0, 18.5% and 14.8%
      respectively) (P<0.05). In cases with positive expression of HIF-lalpha, the
      response rate was 14.3%; whereas in cases with negative expression of HIF-1alpha,
      the response rate was 50.0%. There was significant difference between two groups
      (P<0.05). In patients of HIF-1alpha positive expression,the median progression
      free survival time was 4.7 months,the median survival time was 8.8 months, and 1
      year, 2-year survival rates were 37.5% and 21.5% respectively. In patients of HIF
      1alpha negative expression, the median progression-free survival time was 8.4
      months, the median survival time was l2.6 months, and 1-year, 2-year survival
      rates were 51.2% and 33.5% respectively. There were significant differences
      between two groups (P<0.05). CONCLUSION: HIF-1alpha expression may be a useful
      indicator to predict the chemotherapy response and clinical outcome in gastric
      carcinoma.

PMID- 19742345
TI  - [Effect of siRNA targeting c-Myc and VEGF on human colorectal cancer cells].
AB  - OBJECTIVE: To investigate the biological behavioral effects of specific siRNA
      expression plasmids targeted against c-Myc and vascular endothelial growth factor
      (VEGF) on human colorectal cancer cell line Volo. METHODS: The expression
      plasmids with small interfering RNA (siRNA) aiming at c-Myc and VEGF were
      designed and constructed respectively, then transfected into Volo cells by
      eukaryocyte transfection technique. The protein expressions of c-Myc and VEGF
      were detected by Western blotting. Cellular proliferation, apoptosis, cycle
      distribution and invasion character were analyzed by tetrazolium bromide
      colorimetry (MTT), flow cytometry (FCM), TUNEL assay and matrigel invasion assay
      respectively. RESULTS: Enzymatic digestion and DNA sequencing confirmed that the
      c-Myc and VEGF specific siRNA expression plasmids were constructed successfully.
      After plasmids were transfected into cells, the protein expressions of c-Myc and
      VEGF were significantly down-regulated respectively as compared with control
      group (P<0.01). The cellular proliferation inhibitory rates in c-Myc siRNA group,
      VEGF siRNA group and c-Myc+VEGF group were (59.20+/-5.05)%, (32.31+/-3.48)% and
      (75.81+/-7.89)% respectively, which were higher than that in control group
      [(6.80+/-1.45)%] (all P<0.05). The cell apoptosis rate in above 3 groups were
      (40.50+/-4.37)%, (21.30+/-2.98)% and (62.59+/-9.66)% respectively, which were
      higher than that in control group [(2.90+/-0.36)%] (all P<0.05). The cell
      invasion rates in VEGF siRNA group and c-Myc+VEGF siRNA group were (7.34+/-3.65)%
      and (2.80+/-1.02)%, which were lower than that in control group [(18.57+/-7.46)%]
      (P<0.05). The effect of c-Myc+VEGF siRNA group was greater. CONCLUSIONS: The
      specific siRNA efficiently silences the expression of c-Myc and VEGF,
      subsequently, suppresses the cell proliferation, triggers the cell apoptosis and
      inhibits the cell invasiveness in these transfected colorectal cancer Volo cells.
      In addition, the synergism of siRNA-c-Myc and siRNA-VEGF in transfected cells can
      be found.

PMID- 19742346
TI  - [Distribution of mast cells and its role in the pathogenesis of Hirschsprung
      disease].
AB  - OBJECTIVE: To investigate the distribution of mast cells (MC) in colon tissue of
      Hirschsprung disease (HD) and explore the role of mast cells in the pathogenesis
      of HD. METHODS: Forty-one cases of HD (male 23, female 18), age from 2 months to
      15 years, and eight age-matched normal cases were enrolled in this study. The
      distribution of MC in all layers of colon was examined by immunohistochemistry
      with mouse antihuman mast cell tryptase monoclonal antibody. RESULTS: The count
      of MC in all layers of colon aganglionic segments of HD was significantly higher
      as compared with colon ganglionic segments of HD and normal controls (21.47+/
      3.59 vs 3.18+/-0.87, 2.75+/-0.51). The average optical density values(A) of MC in
      aganglionic and ganglionic segments significantly decreased as compared to normal
      control (0.38+/-0.10,0.31+/-0.11 vs 0.51+/-0.08). CONCLUSION: Mast cells may play
      an important role in the pathogenesis of HD.

PMID- 19742347
TI  - [Expression of lymphatic vessel endothelial hyaluronan receptor-1 in human
      colorectal cancer and its clinical significance].
AB  - OBJECTIVE: To examine the expression of lymph vessel endothelial hyaluronan
      receptor-1 (LYVE-1) in human colorectal carcinoma and to evaluate the
      relationship of LYVE-1 with lymph mode metastasis and prognosis. METHODS: Colonic
      cancer samples of 40 cases were collected. The expression of LYVE-1 was
      determined by RT-PCR and quantified by real-time quantitative PCR. LVD and MVD
      were detected by immunohistochemistry staining. The relationship of LYVE-1 and
      LVD with lymph mode metastasis and prognosis were analyzed. All the patients were
      followed up for at least 3 years. RESULTS: The expression of LYVE-1 and the count
      of LVD were significantly higher in tumor tissue than those in common colon
      tissue (P<0.05). In the majority of tumors, the higher count of LVD indicated
      lymphangiogenesis. The recurrence rates in low LVD group and high LVD group were
      46.7% and 60.0% respectively (P<0.05). The survival rates in the above two groups
      were 90.1% and 56.7% respectively (P<0.05). No significant correlation was found
      between LYVE-1 and recurrence rate (P>0.05) or overall survival (P>0.05).
      CONCLUSION: LYVE-1 indicates an increase of lymphangiogenesis in colorectal
      carcinoma and LVD can be used to evaluate the prognosis for colorectal cancer
      patients.

PMID- 19742348
TI  - [Differential expression of guanylin in colorectal cancer].
AB  - OBJECTIVE: To investigate the expression of guanylin in colorectal cancer.
      METHODS: The expression of guanylin was examined by RT-PCR and semiquantitative
      analysis in 20 cases of colorectal cancer, and its relationship with clinical
      characteristics was analyzed. RESULTS: The positive expression of guanylin in
      normal tissue (80%, 16/20) was significantly higher than that in tumor tissue
      (35%, 7/20) (P<0.01). The same result was found in the semiquantitative analysis
      of 14 cases with differential expression. Differential expression of guanylin in
      colorectal cancer was associate with TNM stage (P<0.05), not with sex, Borrmann
      type and degree of differentiation (all P>0.05). CONCLUSION: There is
      differential expression of guanylin in colorectal cancer, and this kind of
      differential expression is associated with tumor TNM stage.

PMID- 19742349
TI  - [Cellular immunity induced by CD40 ligand-activated dendritic cells in CEA
      transgenic mice].
AB  - OBJECTIVE: To investigate the role of CD40 ligand (CD40L) in dendritic cells (DC)
      of CEA transgenic mice and to evaluate the specific cellular immunity induced by
      activated DC. METHODS: Bone marrow cells of the CEA transgenic mice were used to
      generate immature dendritic cells under the condition of GM-CSF and IL-4. CD40L
      was added to activate dendritic cells into mature phenotype. Dendritic cells
      cancer vaccine was pulsed with CEA526-533 peptide which made the vaccine specific
      for cancer immunity. The immunophenotype molecules were identified by flow
      cytometry. The cytokines produced by cells were determined by ELISA. T cells
      proliferation was measured by (3)H-thymidine essays. RESULTS: Immunophenotype
      molecules expressions of CD40L-activated dendritic cells were significantly
      higher than those in control group. IL-12 secretion by CD40L-activated dendritic
      cells was (937.81+/-51.99) pg/10(6) DC, significantly higher than that in control
      group [(83.06+/-8.58) pg/10(6) DC, P<0.01]. CD8(+) T cells proliferation induced
      by CD40 L-activated dendritic cells was stronger as compared to control group
      (P<0.05), and the secretion of IFN-gamma was(33.900+/-4.550) ng/L, significantly
      higher than that in control group [(5.226+/-0.460) ng/L, P<0.01]. Splenocytes
      proliferation induced by CD40 L-activated dendritic cells was stronger as
      compared to control group (P<0.01), and the secretion of IFN-gamma was (69.802+/
      11.407) ng/L, significantly higher than that in control group [(2.912+/-0.562)
      ng/L, P<0.01]. CONCLUSION: The method of using CD40L to stimulate bone marrow
      delivered dendritic cells promotes the maturation and activation of dendritic
      cells, which enhances the cellular immunity in CEA transgenic mice.

PMID- 19742350
TI  - [Effect of enteral supplement of arginine on intestinal adaptation and its
      mechanism in experimental rats with short bowel syndrome].
AB  - OBJECTIVE: To evaluate the effect of enteral supplement of arginine on intestinal
      adaptation in rats with short bowel syndrome (SBS) and to study its mechanism.
      METHODS: SD rats were randomly assigned to three groups: sham rats (Con), SBS
      rats (SB) and SBS rats supplemented with enteral arginine (SB-Arg). All the
      animals received isonitrogenic and isocaloric enteral nutrition, except that SB
      Arg rats received enteral nutrition supplemented with arginine (300 mg kg(-1) d(
      1)). Fat absorbability, plasma free fatty acids, parameters of intestinal
      adaptation, enterocytes proliferation and apoptosis were determined. RESULTS:
      After massive small bowel resection, rats had significant bowel adaptation.
      Compared with SB rats, SB-Arg rats demonstrated a significant increase in fat
      absorbability [(84.9+/-3.2)% vs [(81.3+/-3.9)%], plasma level of free fatty acids
      [(650.0+/-86.5) vs (289.5+/-76.9) mg/L], ileal mucosal weight [(18.0+/-3.5) vs
      (13.5+/-3.0) mg cm(-1) 100 g(-1)], ileal DNA content [(29.6+/-3.3) vs (26.0+/
      2.6) microg cm(-1) 100 g(-1)], jejunal mucosal protein content [(65.5+/-7.3) vs
      (59.8+/-6.2) microg cm(-1) 100 g(-1)], ileal mucosal protein content[(39.2+/-2.3)
      vs(35.4+/-2.3) microg cm(-1) 100 g(-1)], jejunal mucosal proliferation index
      [31+/-4 vs 22+/-3] and ileal mucosal proliferation index [32+/-2 vs 25+/-3] (all
      P<0.05). Moreover, jejunal and ileal villus length, crypt depth and mucosal
      thickness in SBS-Arg rats were higher than those in SB rats (P<0.05).
      CONCLUSIONS: In rat SBS model, enteral supplement of arginine appears to
      stimulate intestinal structural and functional adaptation. The mechanism may be
      that arginine can stimulate enterocyte proliferation and inhibit enterocyte
      apoptosis.

PMID- 19742351
TI  - Although women are less likely to be admitted to coronary care units, they are
      treated equally to men and have better outcome. A prospective cohort study in
      patients with non ST-elevation acute coronary syndromes.
AB  - BACKGROUND: The aim of this study was to assess gender differences in admission
      level of care, management and outcome in patients with non ST-elevation acute
      coronary syndromes (NSTE-ACS), initially admitted to either coronary care units
      (CCU) or general wards. METHOD: Patients admitted to CCUs were routinely
      registered in the RIKS-HIA registry. In addition, patients admitted to general
      wards with suspected ACS were also identified and registered. Multivariable
      regression analysis was used to adjust for baseline differences between the
      genders. RESULTS: We included 570 consecutive patients with a discharge diagnosis
      of NSTE-ACS. Women were less likely to be admitted to coronary care units (56%
      versus 69%, P=0.002), even after adjustment (odds ratio (OR), 0.65; 95%
      confidence interval (CI): 0.43-0.98). After adjustment for differences in
      baseline characteristics, women were treated similarly to men. We found no
      significant differences in crude short-, or long-term mortality between the
      genders. However, adjustment for background characteristics revealed lower one
      year mortality in women (OR: 0.58; 95% CI: 0.34-0.99). CONCLUSION: In this study
      on patients with NSTE-ACS, women were less likely to be admitted to coronary care
      units. However, the overall treatment was as intensive for women as for men.
      Moreover, after adjustment, one-year mortality was lower in women.

PMID- 19742352
TI  - Does admission NT-proBNP increase the prognostic accuracy of GRACE risk score in
      the prediction of short-term mortality after acute coronary syndromes?
AB  - BACKGROUND: NT-proBNP has prognostic implications in heart failure. In acute
      coronary syndromes (ACS) setting, the prognostic significance of NT-proBNP is
      being sought. We studied short-term prognostic impact of admission NT-proBNP in
      patients admitted for ACS and in association with GRACE risk score (GRS). METHODS
      AND RESULTS: We studied 1035 patients admitted with ACS. Patients were divided in
      quartiles according to NT-proBNP levels on admission: Q1 <180 pg/ml; Q2 180-691
      pg/ml; Q3 696-2664 pg/ml; Q4 2698-35 000 pg/ml. Groups were compared in terms of
      short-term all-cause mortality. Patients with higher NT-proBNP had worst GRS on
      admission. They also received less aggressive treatment. In-hospital mortality
      was 0.8%, 3.0%, 5.8% and 12.8% (P<0.001) and 30-day mortality 1.6%, 4.6%, 6.5%
      and 16.7% (P<0.001) respectively. In multivariate logistic regression analysis,
      NT-proBNP is an independent predictor of in-hospital (OR 2.35; 95% CI: 1.12-4.93,
      P=0.022) and 30-day mortality (OR 2.20; 95% CI: 1.17-4.12, P=0.014). However, NT
      proBNP does not add any incremental benefit to GRS for prediction of outcome by
      ROC curve analysis. CONCLUSIONS: NT-proBNP is an independent predictor of in
      hospital and 30-day mortality after ACS, independently of left ventricular
      function, but does not increase the prognostic accuracy of GRS.

PMID- 19742353
TI  - Coronary artery perforation in patients undergoing percutaneous coronary
      intervention: a single-centre report.
AB  - The present study reports the incidence, management and clinical outcome of
      coronary perforations in 5 of 2991 patients (0.1%) undergoing percutaneous
      coronary intervention, with non-debulking (percutaneous transluminal coronary
      angioplasty and stent) techniques. There was 1 type I, 1 type II and 3 type III
      perforations. One perforation was guidewire related, 2 perforations occurred
      after stent deployment and two occurred during stent-post dilatation with
      balloons. Restoration was obtained by prolong balloon inflation in three cases.
      Subsequent cardiac tamponade occurred in 2 patients, requiring
      pericardiocentesis. One patient died in the cath lab. due to electromechanical
      dissociation. At follow-up, 3 out of 4 patients were asymptomatic and one had
      bypass surgery for restenosis. Treatment of coronary perforation requires rapid
      detection, angiographic classification, and immediate occlusion of perforation
      site, pericardiocentesis, haemodynamic support and reversal of heparin
      anticoagulation.

PMID- 19742354
TI  - Mechanical circulatory support in the ICCU.
AB  - The mortality of acute heart failure (AHF) remains high despite advances in
      treatment. Mechanical circulatory support (MCS) can be applied in AHF, refractory
      to conventional measures, to improve outcomes. This article aims to describe the
      current and the prospective role of MCS in the treatment of AHF. The support
      strategies and the indications of MCS are continuously evolving, including
      situations considered as contraindications in the past. Appropriate patient
      selection, advanced device technology and improved patient management have
      contributed to the substantially improved results. Evolution in device technology
      results in evolution of the clinical applications of MCS. Earlier application of
      MCS, with novel, flexible and individualized support strategies is now feasible.
      Bridging to recovery is the most intriguing support strategy and bridging to
      future treatments is feasible with long-term support. The progressively expanding
      role of MCS in the treatment of heart failure is not reflected in the existing
      guidelines. Being reserved for refractory heart failure, MCS has been applied to
      the sickest patients who were less amenable to randomization. This explains the
      lack of robust evidence, but also highlights the value of the progressively
      improving results. The anticipated wider application of MCS should be better
      defined, systematically recorded, and guided.

PMID- 19742355
TI  - Autofluorescent chalcedony in human brains from elderly patients.
AB  - Chalcedony, a microcrystalline form of silica (SiO(2)), has been found in the
      human brains of elderly patients by using a standard optical petrographic
      microscope. We document here our visualization of chalcedony using a Leica TCS -
      SP2 confocal laser scanning microscope. Sections of human brain were collected
      after autopsy from elderly patients. The autofluorescent character of chalcedony
      allowed us to obtain three-dimensional images of the crystals and mature
      prismatic quartz (chalcedony) was observed. Chalcedony occurred as rhombohedral
      (trigonal) crystals approximately 30 microm in size distributed in patches or
      aggregates. A less mature silica polymorph of about 1- 2 microm in size was
      detected near the crystals. This is the first time that biogenically-produced
      crystalline mineral as autofluorescent crystal aggregates has been observed in
      the human central nervous system of elderly patients using confocal laser
      scanning microscopy.

PMID- 19742356
TI  - Fumonisin B(2) production by Aspergillus niger from grapes and natural occurrence
      in must.
AB  - Aspergillus niger has been recently found to produce fumonisin B(2) (FB(2)).
      Thirty-one strains belonging to four Aspergillus species isolated from grape were
      evaluated for FB(2) production on agar plates. Four out of eight strains of A.
      niger produced FB(2) (29-293 microg g(-1)). None of the strains of A. uvarum (n =
      7), A. tubingensis (8) and A. carbonarius (8) produced detectable amounts of
      toxin. The capability to produce FB(2) was also confirmed by some A. niger
      strains artificially inoculated on grape berries. Natural occurrence of FB(2), at
      levels of 0.01 and 0.4 microg ml(-1), was found in two samples of must collected
      in Apulian cellars in 2007. This is the first report of FB(2) contamination in
      must. These findings suggest that there is a potential risk of exposure to FB(2)
      in the grape-wine chain for consumers and that A. niger may represent the major
      fumonisin-producing species among black Aspergilli occurring on grapes.

PMID- 19742360
TI  - Knowledge/access/risks/benefits/choice: informed consent versus informed non
      compliance.

PMID- 19742361
TI  - Compliance and self-reported barriers to follow-up of abnormal screening
      mammograms among women utilizing a county mobile mammography van.
AB  - Our primary objective was to describe the follow-up patterns for abnormal
      screening mammograms among women in a large urban county who utilized mobile
      mammography. We conducted a retrospective cohort analysis using electronic
      records, medical chart review, and questionnaires. Compliance with diagnostic
      evaluation was 43% to 60%. Among women who did have follow-up, more than 40% did
      not do so in a timely fashion. Younger women and those with less suspicious
      mammograms were more likely to have longer delays. We concluded that programs
      that utilize mobile mammography should include intensive, multilingual tracking
      systems in order increase diagnostic follow-up for this vulnerable population.

PMID- 19742362
TI  - Thai female adolescents' perceptions of dating violence.
AB  - We explored how Thai female adolescents describe the meaning and context of
      dating violence. Twenty-four students, aged 15-17, were purposively recruited
      from a secondary school in Bangkok for individually audio-taped interviews. The
      interviews lasted 45- 70 minutes. ATLAS ti 5.2 was selected for content analysis.
      Five themes emerged, including characteristics of adolescent romantic
      relationships, influences on adolescent romantic relationships, perceptions of
      dating violence, cycle of dating-violence experiences, and influences on
      adolescents' perceptions of dating violence. The findings indicate a foundation
      for developing culturally sensitive programs for dating-violence prevention among
      Thai adolescents.

PMID- 19742363
TI  - Brief research report: uncertainty-inducing and reassuring facts about HPV: a
      descriptive study of French Canadian women.
AB  - We sought to describe information that makes women feel (1) uncertain and (2)
      reassured about their human papillomavirus (HPV) status and the potential health
      implications of an HPV DNA test result and (3) to examine information seeking
      after receiving their result. Thirty women (previously tested HPV negative) read
      factual information on HPV and cervical cancer and were asked which facts were
      uncertainty inducing and which were reassuring. Twenty-four facts reassured women
      of their HPV negative status, 11 facts made women feel uncertain, and 10 facts
      made them feel both. The most common reason for seeking information in the future
      was receiving a positive test result. The authors outline what specific facts
      about HPV health providers can emphasize to alleviate anxiety and encourage women
      to feel reassured of their low cancer risk following a negative test result.

PMID- 19742364
TI  - Hazarding health: experiences of body, work, and risk among factory women in
      Malaysia.
AB  - In the 1970s, Malaysia launched an export-oriented development strategy as a
      means of financing the nation's modernization. The success of the strategy hinged
      significantly on intensive recruitment of women for factory employment. I draw on
      descriptive qualitative research, including interviews (51), surveys (106), and
      ethnography in Malaysia to investigate factory women's experiences of work and
      work-related health risks. Discourse analysis surfaced a latent consciousness of
      bodily changes in relation to work. A grounded theory analysis showed a
      compromised access to occupational risk knowledge that may bear negatively on
      women's well-being and the role women's new labor identities played in mediating
      the meanings of work and risks. Given the predominance of women workers in low
      end manufacturing globally, I aimed to contribute to theoretical and applied
      understandings of gender, globalization, and health.

PMID- 19742365
TI  - Menopausal symptom experience of Hispanic midlife women in the United States.
AB  - Using a feminist approach, we examined the menopausal symptom experience of
      Hispanic midlife women in the United States This was a qualitative online forum
      study among 27 Hispanic midlife women in the United States. Seven topics related
      to menopausal symptom experience were used to administer the 6-month online
      forum. The data were analyzed using thematic analysis. Four themes were
      identified: (a) "Cambio de vida (change of life)," (b) "being silent about
      menopause," (c) "trying to be optimistic," and (d) "getting support." More in
      depth studies with diverse groups of Hispanic women are needed while considering
      family as a contextual factor.

PMID- 19742366
TI  - Childbearing and contraceptive decision making amongst Afghan men and women: a
      qualitative analysis.
AB  - Afghanistan has one of the highest maternal mortality ratios and lowest
      contraceptive prevalence rates globally. Limited information is known regarding
      Afghan men and women's attitudes toward childbearing, child spacing, and
      contraceptive use, which is essential for delivery of appropriate services. We
      conducted a qualitative study among postpartum couples enrolled at maternity
      hospitals in Kabul, Afghanistan. We identified important themes that highlight
      the complex inter-relationship between acknowledged risks of childbearing, desire
      for family planning, rationales for limited contraceptive use, and sociocultural
      barriers to contraceptive use. We offer practical recommendations for application
      of findings toward family planning and maternal mortality reduction programs.

PMID- 19742367
TI  - New perspectives on eating disorders.

PMID- 19742368
TI  - Internet versus face-to-face therapy: emotional self-disclosure issues for young
      adults.
AB  - The purpose of this study was to compare differences in emotional self-disclosure
      between young adult Internet users who prefer face-to-face therapy to those who
      prefer Internet therapy. A convenience sample of 328 was recruited from Facebook
      to complete an online survey. A total of 263 preferred face-to-face therapy
      (F2FT) while 65 preferred Internet therapy (IT). Significant differences were
      found with the F2FT group willing to disclose emotions of depression, jealously,
      anxiety, and fear to a therapist more frequently than the IT group. The majority
      reported a preference for F2FT over IT. Recommendations for future professional
      practice and research are included.

PMID- 19742369
TI  - Experiences of guilt as a mother in the context of eating difficulties.
AB  - The aim of this study was to explore motherhood in the context of eating
      difficulties. The research question was: What are mothers' daily life experiences
      when suffering from ED? An explorative design was used. In-depth interviews (n =
      8) focused on experiences of motherhood and eating difficulties. Data were
      interpreted by hermeneutic analysis. The main theme, "experiencing guilt as a
      mother in the context of eating difficulties," comprised two themes: (1) having a
      guilty conscience in relation to being a good enough mother and (2) being
      preoccupied about not involving the children in the eating difficulties. The
      study illuminates the importance of identifying mothers with eating difficulties
      and offering them treatment and support.

PMID- 19742370
TI  - Turning the coin--emphasizing the opportunities in mental health nursing.
AB  - It is widely acknowledged that mental health nursing has undergone considerable
      change in Australia during recent decades, including the mainstreaming of mental
      health services into the general health care system. Recruitment problems and
      high levels of stress and burnout associated with the profession are seen to be
      indicative of a degree of demise in the status and desirability of this field of
      practice. However, new nursing roles have developed in response to these changes.
      The aim of this paper is to focus on three specific roles: mental health
      consultation-liaison nursing; mental health nurse practitioner; and the mental
      health nurse incentive program. These new roles present exciting and rewarding
      career opportunities for mental health nurses and may increase the attractiveness
      of mental health nursing for new graduates.

PMID- 19742371
TI  - Primary mental health care information and services for St. John's visible
      minority immigrants: gaps and opportunities.
AB  - This article draws on an environmental scan and interviews with visible minority
      immigrants in a small urban Atlantic community to report on gaps and
      opportunities for improving access to information about primary mental health
      care services and barriers to utilization of these services. Information about
      services was limited and did not specifically address the complex health-related
      concerns of immigrants with diverse religious and cultural backgrounds. Accessing
      information about mental health care services was challenging for some visible
      minority immigrants because of physical and financial constraints and limited
      computer and language literacy. The major barriers to the utilization of primary
      mental health care services were lack of information, language and literacy
      issues, a mistrust of primary mental health care services, the stigma associated
      with mental illness, long wait times, lack of finances, and religious and
      cultural differences and insensitivity. A list of nine recommendations, which may
      be of interest to mental health decision-makers and service providers in small
      urban centers with limited ethno-cultural diversity, is provided.

PMID- 19742372
TI  - Homelessness, a state of mind?: a discourse analysis.
AB  - This article presents a discourse analysis of a woman's written account of mental
      illness and homelessness. In her preparation as a co-presenter at a conference
      for decision- and policy-makers, Anna wrote eight distinct drafts of her speaking
      notes; each time emphasizing different aspects of her experiences with mental
      illness and homelessness. By sharing her preparatory writings, Anna offers a rare
      insight into the 'evolution' of the thinking that went into representing her
      story to an audience of professionals. In addition, this analysis represents an
      interpretation and alternative forum to learn from Anna's story.

PMID- 19742373
TI  - Personality disorder prevalence and treatment outcomes: a literature review.
AB  - Personality disorder is argued to be the most prevalent psychiatric disorder and
      is considered to be a significant public health burden, yet there is little
      evidence that the disorder occupies a commensurate place in public health service
      planning, appropriate to such a burden. This paper reviews the prevalence and
      treatment outcome studies of individuals with personality disorder. The
      literature search highlighted prevalence studies and evidence based
      pharmacological, psychosocial, and alliance based interventions within this area.
      From this review, the place of mental health nurses within health service models
      is discussed.

PMID- 19742375
TI  - Cultural explanations of mental health and illness.

PMID- 19742374
TI  - Young children's video/computer game use: relations with school performance and
      behavior.
AB  - This study examined the amount and content of children's video game playing in
      relation with behavioral and academic outcomes. Relationships among playing
      context, child gender, and parental monitoring were explored. Data were obtained
      through parent report of child's game play, behavior, and school performance.
      Results revealed that time spent playing games was related positively to
      aggression and negatively to school competence. Violent content was correlated
      positively and educational content negatively with attention problems.
      Educational games were related to good academic achievement. Results suggest
      violent games, and a large amount of game play, are related to troublesome
      behavioral and academic outcomes, but educational games may be related to
      positive outcomes. Neither gender nor parental monitoring emerged as significant
      moderators of these effects.

PMID- 19742376
TI  - Personal health records.

PMID- 19742377
TI  - Eating dysfunctions: how long can we survive?

PMID- 19742379
TI  - Ion selectivity of the Kat1 K+ channel pore.
AB  - Kat1 is a highly selective inward-rectifying K(+) channel that opens for extended
      periods under conditions of extreme hyperpolarization. Over 200 point mutants in
      the pore region of the Kat1 K(+) channel were generated and examined in the yeast
      Saccharomyces cerevisiae and Xenopus oocytes to assess the effect of the
      mutations on ion selectivity. Substitutions at the tyrosine of the signature
      sequence G-Y-G resulted in the most significant alterations in ion selectivity,
      consistent with its role in the selectivity filter. However, greater than 80% of
      the mutations throughout the greater pore region also conferred a defect in
      selectivity demonstrating that the entire pore of Kat1 contributes to the ion
      selectivity of this channel. Surprisingly, we identified a novel class of mutant
      channel that conferred enhanced selectivity of K(+) over Na(+). Mutants of this
      class frequently displayed sensitivity to the competing ion Cs(+). This finding
      has led us to speculate that the Kat1 channel pore has evolved to balance not
      only K(+)/Na(+) selectivity, but selectivity over Cs(+), and possibly a wide
      spectrum of potential competing ions.

PMID- 19742380
TI  - The sensitivity of a virtual reality task to planning and prospective memory
      impairments: group differences and the efficacy of periodic alerts on
      performance.
AB  - Executive functions have been argued to be the most vulnerable to brain injury.
      In providing an analogue of everyday situations amenable to control and
      management virtual reality (VR) may offer better insights into planning deficits
      consequent upon brain injury. Here 17 participants with a non-progressive brain
      injury and reported executive difficulties in everyday life were asked to perform
      a VR task (working in a furniture storage unit) that emphasised planning, rule
      following and prospective memory tasks. When compared with an age and IQ-matched
      control group, the patients were significantly poorer in terms of their strategy,
      their time-based prospective memory, the overall time required and their
      propensity to break rules. An examination of sensitivity and specificity of the
      VR task to group membership (brain-injured or control) showed that, with
      specificity set at maximum, sensitivity was only modest (at just over 50%). A
      second component to the study investigated whether the patients' performance
      could be improved by periodic auditory alerts. Previous studies have demonstrated
      that such cues can improve performance on laboratory tests, executive tests and
      everyday prospective memory tasks. Here, no significant changes in performance
      were detected. Potential reasons for this finding are discussed, including
      symptom severity and differences in the tasks employed in previous studies.

PMID- 19742381
TI  - The Collaborative Interactions Scale: a new transcript-based method for the
      assessment of therapeutic alliance ruptures and resolutions in psychotherapy.
AB  - The authors present a new transcript-based method for the assessment of
      therapeutic alliance ruptures and resolutions in psychotherapy-the Collaborative
      Interaction Scale (CIS)-and discuss the structure and theoretical background of
      the scale and the rating procedure. To assess interrater reliability, three
      raters independently evaluated 32 psychotherapy sessions (2,984 patient
      utterances and 2,984 therapist utterances) using the CIS, which demonstrated good
      interrater reliability (average kappa=.66-.81). In evaluating the relationship
      between therapist interventions and patient alliance rupture and collaborative
      processes, the authors found significant correlations between therapist negative
      interventions and patient alliance ruptures and among therapist positive
      interventions, patient collaborative processes, and indirect rupture markers.
      Results indicate that the CIS is a reliable rating system, useful in both
      empirical research and clinical assessments.

PMID- 19742382
TI  - The effect of choice between test anxiety treatment options on treatment
      outcomes.
AB  - Evidence regarding the effect of clients' choice of treatment on treatment
      outcome is inconsistent. This possible effect was examined by presenting
      participants with two treatments of test anxiety: advanced muscle relaxation and
      changing of internal dialogue. Clients (N=73) were allocated to three groups:
      choice (participants chose their preferred treatment), no choice (participants
      were assigned to their preferred treatment but were led to believe they couldn't
      choose the treatment they were assigned to), and wait-list control (participants
      received no treatment until the end of the study). There was a significant linear
      pattern, with the choice group performing better than the no-choice group with no
      feeling of control, which in turn performed better than the control group.
      Limitations and suggestions for future research are discussed.

PMID- 19742383
TI  - Utilizing AMPS ability measures to predict level of community dependence.
AB  - The aim of the study was to examine the efficacy of utilizing Assessment of Motor
      and Process Skills (AMPS) ability measures as evidence for determining level of
      community dependence. The sample for the study was drawn from existing data from
      the AMPS International Project database, and consisted of adults from numerous
      world regions, with varying diagnoses and levels of ability (n=64,466). Findings
      support using ADL motor and process ability measures as evidence of a client's
      level of community dependence. When using ADL motor or process ability measures
      to identify the need for moderate to maximal assistance, the areas under the ROC
      curves were 0.74 (fair discrimination power) and 0.82 (good discrimination
      power), respectively. New ADL motor and process cutoff measures demarcating
      maximum assistance were set at 1.00 logit (sensitivity=0.70, specificity=0.66)
      and 0.70 logit (sensitivity=0.79, specificity=0.69), respectively. While ADL
      process ability continues to be the better predictor, the highest accuracy
      estimates occurred when motor and process decisions matched (n=30,835). For the
      first time, multiple AMPS cutoff measures, demarcating independent in the
      community and in need of maximal assistance, have been proposed.

PMID- 19742384
TI  - Selection of objects and tasks in working memory.
AB  - When people hold several objects (such as digits or words) in working memory and
      select one for processing, switching to a new object takes longer than selecting
      the same object as that on the preceding processing step. Similarly, selecting a
      new task incurs task- switching costs. This work investigates the selection of
      objects and of tasks in working memory using a combination of object-switching
      and task-switching paradigms. Participants used spatial cues to select one digit
      held in working memory and colour cues to select one task (addition or
      subtraction) to apply to it. Across four experiments the mapping between objects
      and their cues and the mapping between tasks and their cues were varied
      orthogonally. When mappings varied from trial to trial for both objects and
      tasks, switch costs for objects and tasks were additive, as predicted by
      sequential selection or resource sharing. When at least one mapping was constant
      across trials, allowing learning of long-term associations, switch costs were
      underadditive, as predicted by partially parallel selection. The number of
      objects in working memory affected object-switch costs but not task-switch costs,
      counter to the notion of a general resource of executive attention.

PMID- 19742385
TI  - The influence of visual contrast and case changes on parafoveal preview benefits
      during reading.
AB  - Reingold and Rayner (2006) showed that the visual contrast of a fixated target
      word influenced its viewing duration, but not the viewing of the next
      (posttarget) word in the text that was shown in regular contrast. Configurational
      target changes, by contrast, influenced target and posttarget viewing. The
      current study examined whether this effect pattern can be attributed to
      differential processing of the posttarget word during target viewing. A boundary
      paradigm (Rayner, 1975) was used to provide an informative or uninformative
      posttarget preview and to reveal the word when it was fixated. Consistent with
      the earlier study, more time was spent viewing the target when its visual
      contrast was low and its configuration unfamiliar. Critically, target contrast
      had no effect on the acquisition of useful information from a posttarget preview,
      but an unfamiliar target configuration diminished the usefulness of an
      informative posttarget preview. These findings are consistent with Reingold and
      Rayner's (2006) claim that saccade programming and attention shifting during
      reading can be controlled by functionally distinct word recognition processes.

PMID- 19742386
TI  - Can the dual-route cascaded computational model of reading offer a valid account
      of the masked onset priming effect?
AB  - The masked onset priming effect (MOPE) refers to the empirical finding that
      target naming is faster when the target (SIB) is preceded by a briefly presented
      masked prime that starts with the same letter/phoneme (suf) than when it does not
      (mof; Kinoshita, 2000, Experiment 1). The dual-route cascaded (DRC) computational
      model of reading (Coltheart, Rastle, Perry, Langdon, & Ziegler, 2001) has offered
      an explanation for how the MOPE might occur in humans. However, there has been
      some empirical discrepancy regarding whether for nonword items the effect is
      limited to the first-letter/phoneme overlap between primes and targets or whether
      orthographic/phonological priming effects occur beyond the first letter/phoneme.
      Experiment 1 tested these two possibilities. The human results, which were
      successfully simulated by the DRC model, showed priming beyond the first
      letter/phoneme. Nevertheless, two recent versions of the DRC model made different
      predictions regarding the nature of these priming effects. Experiment 2 examined
      whether it is facilitatory, inhibitory, or both, in order to adjudicate between
      the two versions of the model. The human results showed that primes exert both
      facilitatory and inhibitory effects.

PMID- 19742387
TI  - Flexible saccade-target selection in Chinese reading.
AB  - As Chinese is written without orthographical word boundaries (i.e., spaces), it
      is unclear whether saccade targets are selected on the basis of characters or
      words and whether saccades are aimed at the beginning or the centre of words.
      Here, we report an experiment where 30 Chinese readers read 150 sentences while
      their eye movements were monitored. They exhibited a strong tendency to fixate at
      the word centre in single-fixation cases and at the word beginning in multiple
      fixation cases. Different from spaced alphabetic script, initial fixations
      falling at the end of words were no more likely to be followed by a refixation
      than initial fixations at word centre. Further, single fixations were shorter
      than first fixations in two-fixation cases, which is opposite to what is found in
      Roman script. We propose that Chinese readers dynamically select the beginning or
      centre of words as saccade targets depending on failure or success with
      segmentation of parafoveal word boundaries.

PMID- 19742388
TI  - Perceptual simulations and linguistic representations have differential effects
      on speeded relatedness judgements and recognition memory.
AB  - We examined the effect of spatial iconicity (a perceptual simulation of canonical
      locations of objects) and word-order frequency on language processing and
      episodic memory of orientation. Participants made speeded relatedness judgements
      to pairs of words presented in locations typical of their real-world arrangements
      (e.g., ceiling on top and floor on bottom). They then engaged in a surprise
      orientation recognition task for the word pairs. We replicated Louwerse's (2008)
      finding that word-order frequency has a stronger effect on semantic relatedness
      judgements than does spatial iconicity. This is consistent with recent
      suggestions that linguistic representations have a stronger impact on immediate
      decisions about verbal materials than do perceptual simulations. In contrast,
      spatial iconicity enhanced episodic memory of orientation to a greater extent
      than word-order frequency did. This new finding indicates that perceptual
      simulations have an important role in episodic memory. Results are discussed with
      respect to theories of perceptual representation and linguistic processing.

PMID- 19742389
TI  - Language effects in addition: How you say it counts.
AB  - This study aimed to investigate the role of language in calculation. Two
      populations were compared, one with a base-10 language, and another (Basque) in
      which number words are constructed by combining multiples of 20 and units or
      teens (e.g., "35" is said "twenty and fifteen"). Experiment 1 asked participants
      to verbally solve additions presented as Arabic digits. Basque participants
      solved the additions that consisted of a multiple of 20 and a teen (e.g., 20 +
      15) faster than controls with identical answers (e.g., 25 + 10). No differences
      were found in the base-10 language group. Experiment 2 replicated this result
      even if participants had to type the answer on a numerical keypad, instead of
      saying it. Hence, the structure of number words in each of the languages
      influenced the way additions were solved, even if language was not necessary for
      conducting the task. Finally, in Experiment 3, both language groups performed a
      numerical comparison task in which no effects of the structure of number words
      were obtained. Results of the three experiments are discussed in light of current
      models of numerical cognition.

PMID- 19742390
TI  - From mild cognitive impairment to Alzheimer's disease - influence of
      homocysteine, vitamin B12 and folate on cognition over time: results from one
      year follow-up.
AB  - BACKGROUND AND PURPOSE: People with mild cognitive impairment (MCI) have higher
      risk of developing dementia than the general population. Currently known risk
      factors for dementia include older age, low education level, gait disorders,
      hippocampal atrophy, and apolipoprotein E allele. Vascular risk factors may
      modify the neurodegenerative process. The aim of this study was therefore to
      assess the influence of vascular (genetic and environmental) risk factors on
      progression to dementia in an MCI group during a one-year period. MATERIAL AND
      METHODS: Fifty-five MCI patients (30 men and 25 women) and 44 controls (25 men
      and 19 women) matched for age, gender and education were studied. Mild cognitive
      impairment was diagnosed according to Petersen criteria (Mayo Clinic Group).
      Neuropsychological evaluation was made. Assessed vascular risk factors included
      hypertension, cardiovascular disease, diabetes, cigarette smoking,
      hyperlipidaemia, hyperhomocysteinaemia with vitamin B12 and folate deficiency.
      Genetic risk factors (APOE polymorphism, C677T and A1298C MTHFR polymorphisms)
      were also assessed. RESULTS: Vascular risk factors were found significantly more
      often in the MCI group (p = 0.041), including APOE4 allele (p = 0.018),
      hyperhomocysteinaemia (p = 0.012) and folate deficiency (p = 0.023). Discriminant
      function analysis showed that only age and hypertension are potential factors
      which may have an influence on progression to dementia in the MCI group within
      one year of prospective observation. CONCLUSION: Vascular risk factors are
      associated with cognitive impairment but do not have a significant influence on
      progression to dementia in the MCI group.

PMID- 19742391
TI  - Assessment of autonomic nervous system in patients with epilepsy in the
      interictal state. A pilot study.
AB  - BACKGROUND AND PURPOSE: Dysfunction of the autonomic nervous system often
      accompanies partial and generalized epileptic seizures. In some epileptic
      patients dysfunction of the autonomic nervous system is also present in the
      interictal state. Cardiovascular autonomic disturbances are possibly associated
      with the pathogenesis of sudden unexpected death in people with epilepsy. The aim
      of the study was to evaluate the autonomic nervous system in patients with
      epilepsy in the interictal state and to assess the clinical usefulness of applied
      methods. MATERIAL AND METHODS: The study was done in 21 patients with epilepsy
      (mean age: 35.9 +/-10.7 years; mean duration of the disease: 16.7 +/-14 years).
      The evaluation of the autonomic nervous system was made using a questionnaire,
      cardiovascular reflex tests (Ewing's battery) and neurophysiological method
      (sympathetic skin response). RESULTS: Abnormal score of the questionnaire was
      present in 57.1% of patients. Cardiovascular autonomic neuropathy (l 2 abnormal
      tests of Ewing's battery) was diagnosed only in 1 patient. Abnormal sympathetic
      skin response was found in 33.3% of patients. Duration of the disease influenced
      the results of Ewing's battery only. CONCLUSIONS: Autonomic dysfunction revealed
      by cardio- vascular tests is present uncommonly in patients with epilepsy in the
      interictal state. The questionnaire is a screening method whose result should be
      confirmed by other tests. The value of sympathetic skin response in diagnosis of
      dysautonomia in epilepsy needs further studies.

PMID- 19742392
TI  - Comparision of results between two different techniques of cranio-cervical
      decompression in patients with Chiari I malformation.
AB  - BACKGROUND AND PURPOSE: A variety of approaches are employed for treatment of
      Chiari I malformation. They differ in extent of cranio-c ervical decompression. A
      technique based on arachnoid preservation and duroplasty was introduced in our
      department in 2001. The aim of the study is to compare between the previous and
      the present technique. MATERIAL AND METHODS: Retrospective analysis of 38
      patients with Chiari I malformation treated between 1998 and 2004 was performed.
      The previous technique including arach- noid incision, coagulation of cerebellar
      tonsils, and fourth ventricle exploration without duroplasty was used to treat 21
      patients (group 1). A further 17 patients were treated with the present technique
      consisting of arachnoid preservation and duroplasty (group 2). Complication rates
      as well as early and late results of treatment were evaluated. Karnofsky (KPS),
      Rankin (RS) and Bidzinski (BS) scales were used for evaluation of results.
      RESULTS: Post-operative complications were detected in 9 patients in group 1
      (43%). They included liquorrhoea (5 cases), meningitis (1 case), and symptoms
      progression (3 cases). There were no surgical complications in group 2 (p =
      0.002). Neurological improvement in the early period (until discharge from
      hospital) occurred in 10 (48%) patients in group 1 and in 13 (76%) in group 2 (p
      = NS). Further improvement or lack of symptoms progression was found in 58% in
      group 1 and 82% in group 2 (p = NS). Assessment in KPS, RS and BS showed slightly
      better results of group 2 but the difference was statistically insignificant.
      CONCLUSIONS: Results of both techniques are comparable. The risk of post
      operative complications after extra-arachnoid cranio-cervical decompression with
      duroplasty is, however, significantly lower.

PMID- 19742393
TI  - The role of FloSeal in reducing epidural fibrosis in a rat laminectomy model.
AB  - BACKGROUND AND PURPOSE: An increased amount of fibrosis formed after lumbar
      surgery may be the underlying cause of the failed back surgery syndrome in most
      cases. Various materials have been used to prevent epidural fibrosis, but only
      limited success has been achieved. In this study, the authors investigated the
      effect of FloSeal (a gelatine-containing thrombin-based haemostatic agent) on
      spinal epidural fibrosis in a rat laminectomy model. MATERIAL AND METHODS:
      Sixteen Wistar rats underwent laminectomy at L4 and L5 levels. In 8 rats, 0.5 mL
      of FloSeal was locally applied to the laminectomy site. The laminectomy site was
      irrigated with saline in the control group of 8 other rats. The rats were
      sacrificed four weeks later. Each specimen was examined for density of fibrosis,
      and both fibroblast and inflammatory cell density. RESULTS: Epidural fibrosis
      density differed significantly between the FloSeal group and the control group.
      Evaluation of the fibroblast density and the inflammatory cell density showed a
      statistically significant difference between the FloSeal group and the control
      group. CONCLUSION: Application of FloSeal at a laminectomy site may be useful to
      decrease adhesion at the interface between the dura mater and epidural fibrosis.

PMID- 19742394
TI  - Serum cortisol levels following acute experimental spinal cord injury.
AB  - BACKGROUND AND PURPOSE: Cortisol has neuroprotective effects. We monitored the
      serum cortisol levels after cervical and thoracic spinal cord injury (SCI) in
      four groups of rats. MATERIAL AND METHODS: Forty male Sprague-Dawley rats were
      randomized to four groups. The control group received neither laminectomy nor
      SCI. The sham group received laminectomy without SCI. The cervical spinal trauma
      group received a C5-C6 laminectomy and spinal trauma at this level. The thoracic
      spinal trauma group received a T6-T7 laminectomy and spinal trauma. Blood samples
      were drawn 2, 6, 12 and 24 hours after surgeries and assayed immediately.
      RESULTS: The level of cortisol in the cervical spinal trauma group was highest at
      the second hour of the experiment and the lowest in control and sham-operated
      groups at the same time. At the sixth hour, cortisol levels increased in control
      and sham-operated groups, decreased in the cervical group and did not change in
      the thoracic group. At the 12th hour, cortisol levels in control and sham
      operated groups decreased, but increased in thoracic and cervical groups. At the
      24th hour, serum cortisol levels in thoracic and cervical groups decreased but
      did not change significantly in control and shamoperated animals. CONCLUSIONS:
      Activation of endogen cortisol secretion of the organism starts immediately after
      the SCI injury and throughout the experiment the serum cortisol levels in
      neurotrauma groups remained high compared with the control and sham-operated
      groups. At the beginning, the level of neurological lesion (cervical or thoracic)
      affected differently the level of serum cortisol at a statistically significant
      level but this difference disappeared at the 6th hour.

PMID- 19742395
TI  - [Essential tremor and parkinsonian tremor long-term monitoring].
AB  - Instrumental methods of tremor investigation can be used in differential
      diagnosis between essential and parkinsonian tremor in uncertain cases. This
      paper describes the method of tremor quantification using long-term surface
      electro- myography registration of antagonistic forearm muscles. Examples of
      clinical application of the method are also given.

PMID- 19742396
TI  - [Laser evoked potentials as a method of evaluating the function of small fibres -
      application technique and clinical implications].
AB  - Laser evoked potentials (LEPs) are one of the few neurophysiological methods
      available whose purpose is to evaluate the functions of small fibres' sensory
      pathways Ad and C. This non-invasive technique is applied at the present time in
      diagnosing small fibre neuropathy. In order to record distinctive and repetitive
      evoked potentials from the surface of the skull, the skin of the dorsal surface
      of the hands and feet is stimulated with laser thermal, nociceptive stimuli. The
      main cortical laser-evoked potential is a complex of components N2-P2. Evaluation
      of the registered potentials in- cludes their morphology with shape, latency and
      amplitude. Up to now, laser evoked potentials have not been performed in Poland.

PMID- 19742397
TI  - [Primary progressive aphasia: primary nonfluent aphasia or logopedic aphasia? A
      case report].
AB  - We present a case of a 58-year-old female suffering from progressive language
      difficulties with characteristic symptoms of primary progressive aphasia (PPA)
      who was finally diagnosed as having progressive nonfluent aphasia variant (PNFA).
      The differential diagnosis was made between a variant of PNFA and logopenic
      variant of PPA occurring often in the course of Alzheimer's disease.

PMID- 19742398
TI  - Isaacs syndrome associated with chronic hepatitis B infection: a case report.
AB  - Isaacs syndrome or acquired neuromyotonia is a disorder of peripheral nerve
      hyperexcitability characterized by regular or irregular myokymia, muscle cramps
      and stiffness, delayed muscle relaxation after contraction, and hyperhidrosis.
      Herein, we report clinical and electrodiagnostic findings of a Persian man with
      Isaacs syndrome associated with chronic hepatitis B infection. In this patient
      hepatitis B virus might have contained an antigen (i.e. surface antigen) which
      has provoked the immune system and has resulted in the production of antibodies
      that could have affected voltage gate potassium channels leading to the
      excitation of muscle fibres as well as the generation of abnormal discharges. The
      improvement of the patient's symptoms after plasma exchange is also in favour of
      the immunological pathogenesis of the disease.

PMID- 19742399
TI  - A case of cerebral toxoplasmosis in a pregnant non-immunocompromised patient.
AB  - Cerebral toxoplasmosis, a disease of immunocompromised individuals, is rare in
      immunocompetent persons. We present a case of cerebral toxoplasmosis in a non
      immunocompro-mised pregnant woman. Her imaging studies revealed a mass lesion
      involving the right basal ganglia, periventricular grey matter, midbrain and pons
      suggesting a neoplastic pathology along with hydrocephalus. She underwent an
      endoscopic third ventriculostomy and biopsy of the lesion. Postoperatively her
      consciousness improved as the hydrocephalus was relieved. After a thorough
      gynaecological examination she gave birth to a healthy child via normal vaginal
      delivery. The histopathology examination of biopsy suggested an inflammatory
      pathology. Serological studies for toxoplasmosis were positive. After 6 weeks of
      anti-toxoplasma treatment follow-up imaging showed a significant decrease in the
      size of the lesion.

PMID- 19742400
TI  - [Internet-based psychotherapy programmes--do they endanger the therapeutic
      relationships in psychiatry and pyschotherapy?].

PMID- 19742401
TI  - [Between Griesinger and Kraepelin--Ludwig Meyer (1827-1900): anatomist and reform
      psychiatrist].
AB  - Ludwig Meyer worked as resident psychiatrist, scientist and university teacher in
      Berlin, Schwetz, Hamburg and for the longest time in Gottingen. He promoted
      social psychiatry, i. e. extramural treatment, "Milieutherapie" within the
      institution and especially the non restraint system. Mention should be made of
      the casuistic works, in which Meyer connected clinical and neopathological
      methods, morphologic studies of progressive paralysis and--beyond psychiatry--the
      discovery of "Progenie" in anatomy. Forensic psychiatry he saw as an expert task
      as well as a medical task. In the training of psychiatrists Meyer broke new
      ground. Ludwig Meyer is the most important representative of the late 19th
      century. His work was mainly influenced by Griesinger's concepts (1868). Within
      the following thirty years Meyer further developed these concepts and added ideas
      of his own. In Meyers works Kraepelin's clinical methods and pluralistic
      psychiatry already shine through.

PMID- 19742402
TI  - [Sports-related carotid artery dissection].
AB  - Sports-related carotid artery dissection are very rare and were described in
      different kinds of sports. We report on a 45-year old man who suffered bilateral
      brain infarctions caused by bilateral extracranial internal carotid artery
      dissection after excessive weight lifting in a gym. As possible trigger factors
      for the dissections we assumed the abrupt extension of the neck during weight
      lifting and the frequent Valsalva manoeuvers with massive rise in the pressure in
      the carotid artery system. The patient underwent angioplasty and stenting of the
      stenosis of right carotid artery, the primarily occluded left carotid artery
      recanalized spontaneously. Secondary prevention was established by platelet
      aggregation inhibitors. The patient recovered completely. The pathogenesis of
      sports-related dissections is multifactorial. In addition to sporting activities
      hereditary or acquired structural aberrations in the arterial walls could be
      discussed. Acute focal neurological symptoms after sport should always focus on
      carotid or vertebral artery dissection.

PMID- 19742403
TI  - Pheochromocytoma.

PMID- 19742405
TI  - Clinical sleep neurology.

PMID- 19742406
TI  - The neurobiology of sleep.
AB  - The neurobiology of sleep and narcolepsy is reviewed. Non-rapid eye movement
      (NREM) sleep is generated by neurons in the preoptic region of the hypothalamus
      and adjacent basal forebrain. Lesions in these regions cause insomnia.
      Stimulation of these regions rapidly produces sleep onset. The key brain
      structure for generating REM sleep is the pons and adjacent portions of the
      midbrain. Damage to the pons and/or caudal midbrain can cause abnormalities in
      REM sleep. The persistent sleepiness of narcolepsy is a result of a loss of
      hypocretin function.

PMID- 19742407
TI  - Approach to the patient with sleep complaints.
AB  - Sleep disorders are both common and consequential, but too often remain
      undiagnosed. The insidious, chronic course of most sleep disorders and lack of
      patient awareness of signs and symptoms during sleep can complicate the clinical
      evaluation. Typical chief complaints include snoring, excessive daytime
      sleepiness, insomnia, and behaviors during sleep. Sleep disorders can be primary
      or secondary to medical, neurologic, or psychiatric conditions, so a
      multidisciplinary approach is often desirable. Family members can be a critical
      source of information as they may have observed nocturnal or daytime symptoms
      unrecognized by the patient. Objective testing plays an important role in
      assessment for obstructive sleep apnea, parasomnias, and other specific sleep
      disorders, and can be used most effectively in combination with a thorough
      clinical evaluation. Nonsleep specialists should consider obtaining assistance
      from sleep clinicians for more challenging presentations or management of sleep
      disorders unfamiliar to them.

PMID- 19742408
TI  - The use of sleep studies in neurologic practice.
AB  - Sleep medicine is a multidisciplinary specialty that is rapidly advancing with
      exciting new discoveries. Some sleep disorders are diagnosed by clinical history
      alone, but others such as sleep apnea, narcolepsy, periodic limb movement
      disorder, parasomnias, and nocturnal seizures (conditions that will be addressed
      by other articles in this issue) usually require evaluation in the sleep
      laboratory. Sleep studies are used for diagnostic purposes, to assess disease
      severity, and to evaluate treatment efficacy. Routine sleep testing can be
      tailored to answer the specific clinical question at hand. In this article, the
      authors review the most commonly performed sleep tests in the sleep laboratory
      and their indications, interpretation, and limitations. These include the
      polysomnogram (PSG), the Multiple Sleep Latency Test (MSLT), the Maintenance of
      Wakefulness Test (MWT), and actigraphy. The accurate interpretation of these
      studies requires a comprehensive sleep and medical history.

PMID- 19742410
TI  - Chronic insomnia.
AB  - Chronic insomnia afflicts millions of people in the United States. It is
      associated with decreased quality of life, accidents, several comorbid
      conditions, increased morbidity, and substantial direct and indirect costs.
      Chronic insomnia is a multifactorial and individualized disorder. Its etiology
      may be cognitive or physiologic in nature (or both), and is more often than not
      associated with a comorbid condition, complicating its recognition, evaluation,
      and treatment. Effective nonpharmacotherapeutic (cognitive-behavioral therapy for
      insomnia) and pharmacotherapeutic (hypnotic medications) treatment modalities are
      available. Treatment of chronic insomnia can make a significant improvement in
      quality of life, and may also be associated with an improvement in comorbid
      conditions.

PMID- 19742411
TI  - Primary hypersomnias of central origin.
AB  - Hypersomnia is a frequently encountered symptom in clinical practice. The
      cardinal manifestation is inappropriate daytime sleepiness, common to all types
      of hypersomnias. Hypersomnias of central origin are a rare cause of excessive
      daytime sleepiness, much rarer than the hypersomnia related to other pathologies,
      such as sleep-disordered breathing. Narcolepsy, with or without cataplexy,
      remains the most well studied of the primary hypersomnias. Although recognized
      more than a century ago, it was not until the end of the 20th century that major
      breakthroughs led to a better understanding of the disease, with hope of more
      specific therapies. The authors review the major aspects of this disorder,
      including the newer treatment modalities. Idiopathic hypersomnia is also part of
      the primary hypersomnias. Although difficult to diagnose, certain peculiarities
      stand out to help us differentiate it from the more commonly seen narcolepsy. The
      recurrent hypersomnias, particularly the Kleine-Levin syndrome, will be
      discussed. This rare disorder has been studied more closely in the last few years
      with abundant epidemiologic data assembled through literature and worldwide case
      reviews. Understanding the primary central hypersomnias warrants a thorough look
      from the original description, as well as a peek at the future, while more
      efficacious diagnostic and therapeutic interventions are currently being
      developed.

PMID- 19742412
TI  - Neurologic aspects of sleep apnea: is obstructive sleep apnea a neurologic
      disorder?
AB  - The upper airway caliber is determined by afferent sensory input to the brainstem
      respiratory centers and efferent motor neural output to the upper airway
      structures. Upper airway caliber is altered in obstructive sleep apnea. The
      mechanosensory receptors of the upper airway are capable of responding to changes
      in airway pressure, airflow, temperature, and to the upper airway muscle tone
      itself. Application of topical anesthesia change chronic snorers in apneic
      patients during sleep and prolong sleep apnea in obstructive sleep apnea (OSA)
      patients. Respiratory-related evoked potential are significantly reduced in OSA
      patients during non-rapid eye movement sleep indicating a sleep-related blunted
      cortical response to inspiratory occlusion. Histologic investigations of
      palatopharyngeal muscles from OSA patients show evidence of motor neuron lesions
      and actual damage to the muscles. Currently demonstrated local neurologic
      impairment and lesions can explain the development of sleep apneas and hypopneas.

PMID- 19742409
TI  - Neurocognitive consequences of sleep deprivation.
AB  - Sleep deprivation is associated with considerable social, financial, and health
      related costs, in large measure because it produces impaired cognitive
      performance due to increasing sleep propensity and instability of waking
      neurobehavioral functions. Cognitive functions particularly affected by sleep
      loss include psychomotor and cognitive speed, vigilant and executive attention,
      working memory, and higher cognitive abilities. Chronic sleep-restriction
      experiments--which model the kind of sleep loss experienced by many individuals
      with sleep fragmentation and premature sleep curtailment due to disorders and
      lifestyle--demonstrate that cognitive deficits accumulate to severe levels over
      time without full awareness by the affected individual. Functional neuroimaging
      has revealed that frequent and progressively longer cognitive lapses, which are a
      hallmark of sleep deprivation, involve distributed changes in brain regions
      including frontal and parietal control areas, secondary sensory processing areas,
      and thalamic areas. There are robust differences among individuals in the degree
      of their cognitive vulnerability to sleep loss that may involve differences in
      prefrontal and parietal cortices, and that may have a basis in genes regulating
      sleep homeostasis and circadian rhythms. Thus, cognitive deficits believed to be
      a function of the severity of clinical sleep disturbance may be a product of
      genetic alleles associated with differential cognitive vulnerability to sleep
      loss.

PMID- 19742413
TI  - Parasomnias and movement disorders of sleep.
AB  - Neurologists are often enlisted to help diagnose, evaluate, and manage a spectrum
      of abnormal spells during the night ranging from parasomnias to motor disturbance
      that span the sleep-wake cycle. Parasomnias are undesirable emotional or physical
      events that accompany sleep. These events typically occur during entry into sleep
      from wakefulness, or during arousals from sleep, and are often augmented by the
      sleep state. Some parasomnias, such as the rapid eye movement (REM) sleep
      behavior disorder may be extremely undesirable, while others such as somniloquy
      are often of little concern. The parasomnias include a spectrum of abnormal
      emotions, movements, behaviors, sensory perceptions, dream mentation, and
      autonomic activity. Basic physiologic drives, such as sex, hunger, and
      aggression, may manifest as sleep-related eating, sleep-related sexual behaviors,
      and sleep-related violence. Parasomnias have a very bizarre nature, but are
      readily explainable, diagnosable, and treatable. They are hypothesized to be due
      to changes in brain organization across multiple states of being, and are
      particularly apt to occur during the incomplete transition or oscillation from
      one sleep state to another. Parasomnias are often explained on the basis that
      wakefulness and sleep are not mutually exclusive states, and abnormal intrusion
      of wakefulness into non-REM (NREM) sleep produces arousal disorders, and
      intrusion of wakefulness into REM sleep produces REM sleep parasomnias and REM
      sleep behavior disorder (RBD). Restless legs syndrome (RLS) and periodic limb
      movement disorder (PLMD), two closely related conditions that often result in
      disturbed sleep onset and sleep maintenance, are also reviewed in this article.
      Although the mechanisms that underlie idiopathic RLS or PLMD are not fully
      understood, there is currently substantial evidence that dopaminergic dysfunction
      is likely involved in both conditions. The discussion will conclude with the
      "other parasomnias" and sleep-related movement disorders of clinical interest to
      the neurologist.

PMID- 19742414
TI  - Circadian rhythm disorders.
AB  - Circadian rhythm sleep disorders occur when individuals attempt to sleep at the
      wrong circadian time. The misalignment between the internal circadian timing
      system and the external environment is typically due to either an alteration in
      the functioning of the circadian timing system (e.g., delayed or advanced sleep
      phase disorder) or to changes in the external environment (e.g., jet lag).
      However, the clinical presentation of most of the circadian rhythm sleep
      disorders is influenced by a combination of physiologic, behavioral, and
      environmental factors. These disorders lead to complaints of insomnia and
      excessive daytime sleepiness, with impairment in important areas of functioning
      and quality of life. Current treatments, such as timed exposure to bright light
      and exogenous melatonin, primarily serve to align the timing of circadian rhythms
      or increase the strength of the circadian signal. Although these treatments are
      effective, their use in clinical practice has been limited by the availability of
      adequate diagnostic tools and large-scale randomized controlled clinical trials.
      The rapid advances in our understanding of the molecular, cellular, and
      physiologic basis of circadian regulation and the pathophysiology of these
      disorders will lead to more targeted and effective treatments.

PMID- 19742415
TI  - Sleep and headache.
AB  - There is a strong interaction between sleep and headache. Sleep and headache
      disorders overlap epidemiologically, and share elements of anatomy and
      physiology. Perhaps as a result, their treatment is often mutually
      interdependent. Despite this, headache and sleep disorders tend to be treated
      separately, by different subspecialties of neurology. The headache disorders and
      their relationship to sleep, the commonalities of headache and sleep
      pathophysiology, and headache disorders that are particularly susceptible to
      sleep modulation (and vice versa) are reviewed. Practical management advice for
      sleep-modulated headaches is provided.

PMID- 19742416
TI  - Sleep and epilepsy.
AB  - Over a century of work has confirmed crucial links between sleep and epilepsy.
      Seizures and some antiepileptic drugs (AEDs) adversely affect the continuity of
      sleep. However, sleep is fragmented in the absence of seizures or medication,
      suggesting that sleep instability may be an inherent component of certain forms
      of epilepsy. In turn, sleep instability can promote seizures, thus forming a
      vicious cycle. Sleep deprivation provokes seizures and epileptiform discharges in
      some people with epilepsy. Synchronized nonrapid eye movement (NREM) sleep
      facilitates seizures, whereas desynchronized rapid eye movement (REM) sleep
      discourages seizure occurrence. The sleep electroencephalogram (EEG) is useful in
      the diagnosis and localization of epilepsy, as new epileptic foci can appear in
      sleep and REM sleep may demonstrate the narrowest localization of the primary
      focus. Polysomnography (PSG) with expanded EEG aids in the differentiation of
      seizures and parasomnias and in the diagnosis of primary sleep disorders, such as
      sleep apnea, that can exacerbate seizures. Treating sleep apnea may lead to
      improved seizure control. These observations underscore the importance of sleep
      in the diagnosis and treatment of people with epilepsy.

PMID- 19742417
TI  - Sleep and neuromuscular disease.
AB  - Sleep disorders in patients with neuromuscular disease are common, but
      underrecognized by health care providers, and sometimes by patients themselves.
      Their symptoms may be confused with those of the underlying disease. Their
      recognition is an important part of the management of patients with neuromuscular
      disorders, improving quality of life, and sometimes increasing survival.
      Inadequate ventilation underlies many sleep disorders, and sleep-related
      disorders may presage daytime ventilatory disorders with disease progression.
      Involvement of the central or peripheral nervous system, or both, may disrupt
      sleep, with the relative contribution of each depending on the specific disorder.
      The pertinent anatomy, physiology, and clinical features of sleep disorders in
      neuromuscular diseases and a basic approach to their assessment is discussed.
      Specific neuromuscular disorders in which sleep is commonly affected are reviewed
      and the principles of management of sleep disorders summarized.

PMID- 19742418
TI  - Sleep and stroke.
AB  - Sleep affects brain function and may contribute to vascular cerebral pathology
      through a diversity of direct and indirect mechanisms. Circadian rhythm
      investigation shows increased incidence of stroke between 6 AM and 12 noon. Risk
      factors for stroke such as high blood pressure, ischemic heart disease, and
      diabetes are modified by sleep and sleep apnea. Epidemiological studies have
      shown a dose-response relationship between the severity of sleep apnea and the
      odds ratio for development of systemic hypertension. There is now evidence of a
      causal relationship between sleep apnea and stroke. Following stroke, both in the
      acute and chronic stages, patients have a high prevalence of sleep apnea that
      reduces the potential for rehabilitation, further increases the risk of secondary
      stroke, and heightens mortality. Successful correction of sleep apnea with
      noninvasive positive airway pressure ventilation lowers mean blood pressure, and
      indirectly lowers the risk of stroke. Unfortunately, patients with stroke
      tolerate positive noninvasive ventilation poorly, and other means of correcting
      sleep apnea need to be investigated.

PMID- 19742419
TI  - Sleep and neurodegenerative diseases.
AB  - Sleep disturbances are common in neurodegenerative diseases. Disturbed sleep can
      result in fatigue, irritability, morning headaches, impaired motor and cognitive
      skills, depression, and daytime somnolence. The major sleep complaints include
      insomnia, hypersomnia, parasomnia, excessive nocturnal motor activity, circadian
      sleep-wake rhythm disturbance, and respiratory dysrhythmia. The pathogenetic
      mechanisms of sleep disturbances may be secondary to direct structural alteration
      of the sleep-wake generating neurons or from several other indirect mechanisms.
      At the biochemical level, neurodegenerative diseases may be largely classified as
      tauopathies, alpha-synucleinopathies, and other diseases. Overnight
      polysomnography (PSG), Multiple Sleep Latency Test, Maintenance of Wakefulness
      Test, and actigraphy are some important diagnostic laboratory tests in the
      evaluation of sleep disturbances. Management of sleep disturbances is complex and
      is based primarily on the nature of the sleep disturbance. The clinical profiles,
      pathogenetic mechanisms, PSG findings, and management issues are discussed here
      with reference to some common neurodegenerative diseases.

PMID- 19742420
TI  - Genomic polymorphism in the interferon-induced helicase (IFIH1) gene does not
      confer susceptibility to autoimmune thyroid disease in the Japanese population.

PMID- 19742421
TI  - The use of ultrasound to detect small-for-gestational-age infants in patients
      with elevated human chorionic gonadotropin on maternal serum screening.
AB  - We evaluated serial sonography for the antenatal detection of small-for
      gestational-age (SGA) infants in pregnancies with elevated human chorionic
      gonadotropin (hCG) levels on midtrimester triple-marker screen. A retrospective
      cohort study was performed at Saddleback Memorial Medical Center where serial
      ultrasounds from 26 weeks to delivery are generally recommended for patients with
      hCG levels >2.0 Multiple of the Median (MoM). From 1999 to 2007, 659 subjects
      were identified for analysis. The incidence of intrauterine growth restriction
      (IUGR) and SGA were 5.2% and 7.3%, respectively. Antenatal ultrasound identified
      31.3% of SGA infants. Compared with estimated fetal weight (EFW) <10th percentile
      alone, abdominal circumference (AC) <10th percentile improved the detection of
      SGA from 31.3% (95% confidence interval [CI], 18.7 to 46.3) to 35.4% (95% CI,
      22.2 to 50.5). Using either EFW or AC further increased the sensitivity to 45.8%
      (95% CI, 31.4 to 60.8). The sensitivity for the detection of SGA was 100% when an
      EFW cutoff of 75% was used. Ultrasound can be used to detect SGA infants in
      patients with elevated hCG levels on midtrimester serum screening. A sonographic
      estimated fetal weight > or = 75th percentile appears to be a safe cutoff to rule
      out all fetuses at risk for SGA.

PMID- 19742422
TI  - Pentacyclic triterpenes of the lupane, oleanane and ursane group as tools in
      cancer therapy.
AB  - Today cancer treatment is not only a question of eliminating cancer cells by
      induction of cell death. New therapeutic strategies also include targeting the
      tumour microenvironment, avoiding angiogenesis, modulating the immune response or
      the chronic inflammation that is often associated with cancer. Furthermore, the
      induction of redifferentiation of dedifferentiated cancer cells is an interesting
      aspect in developing new therapy strategies. Plants provide a broad spectrum of
      potential drug substances for cancer therapy with multifaceted effects and
      targets. Pentacyclic triterpenes are one group of promising secondary plant
      metabolites. This review summarizes the potential of triterpenes belonging to the
      lupane, oleanane or ursane group, to treat cancer by different modes of action.
      Since Pisha et al. reported in 1995 that betulinic acid is a highly promising
      anticancer drug after inducing apoptosis in melanoma cell lines in vitro and in
      vivo, experimental work focused on the apoptosis inducing mechanisms of betulinic
      acid and other triterpenes. The antitumour effects were subsequently confirmed in
      a series of cancer cell lines from other origins, for example breast, colon, lung
      and neuroblastoma. In addition, in the last decade many studies have shown
      further effects that justify the expectation that triterpenes are useful to treat
      cancer by several modes of action. Thus, triterpene acids are known mainly for
      their antiangiogenic effects as well as their differentiation inducing effects.
      In particular, lupane-type triterpenes, such as betulin, betulinic acid and
      lupeol, display anti-inflammatory activities which often accompany immune
      modulation. Triterpene acids as well as triterpene monoalcohols and diols also
      show an antioxidative potential. The pharmacological potential of triterpenes of
      the lupane, oleanane or ursane type for cancer treatment seems high; although up
      to now no clinical trial has been published using these triterpenes in cancer
      therapy. They provide a multitarget potential for coping with new cancer
      strategies. Whether this is an effective approach for cancer treatment has to be
      proven. Because various triterpenes are an increasingly promising group of plant
      metabolites, the utilisation of different plants as their sources is of interest.
      Parts of plants, for example birch bark, rosemary leaves, apple peel and
      mistletoe shoots are rich in triterpenes and provide different triterpene
      compositions.

PMID- 19742423
TI  - Japonicones E-L, dimeric sesquiterpene lactones from Inula japonica Thunb.
AB  - Eight new dimeric sesquiterpene lactones (japonicones E-L, 1- 8), including a
      novel sesquiterpene dimer bearing a rare hydroperoxide group (japonicone E, 1),
      were isolated from the aerial part of Inula japonica Thunb. Their structures were
      determined mainly by the use of 1D and 2D NMR spectroscopic techniques including
      HSQC, (1)H-(1)H COSY, HMBC, and NOESY. All the isolates were tested for
      inhibitory effects against LPS-induced NO production in RAW264.7 macrophages.
      Among the compounds tested, japonicone F (2) showed the strongest activity with
      the IC(50) value of 4.1 microg/mL.

PMID- 19742424
TI  - Antifeedant and cytotoxic activity of longipinane derivatives.
AB  - The polyoxygenated longipinane derivatives 1- 8 were tested as antifeedant
      compounds against the herbivorous insects Spodoptera littoralis, Rhopalosiphum
      padi, and Myzus persicae. Compounds 1-3 and 8 exhibited significant antifeedant
      activity against S. littoralis and M. persicae. The antifeedant activity against
      S. littoralis increased moderately after the C-8 hydroxy group in 3 was removed
      to afford 1 and increased strongly after the remaining two hydroxy groups were
      acetylated to afford 2. Compound 1 was active on M. persicae. Compounds 1, 3, and
      4, with an unsaturated six-membered ring, exhibited an increase in post-ingestive
      effects on S. littoralis ranging from antifeedant in the case of 1 to toxic for
      compounds 3 and 4. These compounds did not have any phytotoxic effect on Lactuca
      sativa. When tested on a panel of tumoral cells, compounds 2 and 6 exhibited
      moderate selective cytotoxic effects on the p53 null lung carcinoma cells H1299,
      which were not affected by the drug paclitaxel. In addition, vibrational circular
      dichroism (VCD) was applied to the representative longipinene derivative 2 to
      verify its absolute configuration, and the sensitivity of the VCD methodology was
      evaluated by comparing spectra of the three diastereoisomers (4 R,5 S,7 R,9 R,10
      R,11 R)-7,9-diacetyloxylongipin-2-en-1-one (2), (4 R,5 S,7 S,9 R,10 R,11 R)-7,9
      diacetyloxylongipin-2-en-1-one, and (4 R,5 S,7 R,9 S,10 R,11 R)-7,9
      diacetyloxylongipin-2-en-1-one.

PMID- 19742425
TI  - Alpha-glucosidase inhibitory, aromatase inhibitory, and antiplasmodial activities
      of a biflavonoid GB1 from Garcinia kola stem bark.
AB  - The biflavonoid, 3'',4',4''',5,5'',7,7''-heptahydroxy-3,8-biflavanone, known as
      GB1 (1), was isolated as a major constituent from Garcinia kola stem bark. GB1
      (1) exhibited alpha-glucosidase and aromatase inhibitory activities, as well as
      antiplasmodial activity, but was not toxic against cell lines tested. GB1 (1) may
      be a potential dietary supplement or phytomedicine for the prevention of breast
      cancer and type 2 diabetes mellitus.

PMID- 19742426
TI  - Preoperative computed tomographic angiogram for deep inferior epigastric artery
      perforator flap breast reconstruction.
AB  - Precision in preoperative evaluation of the abdominal wall vascular anatomy is of
      utmost importance in successful planning and execution of perforator flap surgery
      for breast reconstruction after mastectomy. We performed a study in 357 patients
      scheduled for deep inferior epigastric artery perforator (DIEAP) flap breast
      reconstruction to review our 5-year experience with the technique we developed
      based on our previous research confirming accuracy of a computed tomographic (CT)
      angiogram (multidetector row computed tomography [MDCT]) in preoperative planning
      of abdominal perforator flap surgery. Images obtained from the radiological study
      were used to create an accurate map of dominant abdominal perforators of the deep
      inferior epigastric artery, showing their location, size, and anatomic
      considerations of relevance for the preoperative flap design. Anatomic dissection
      of all perforators was performed in the first 36 cases to compare the data with
      preoperative MDCT findings. In the following 321 patients, the dominant
      perforator was chosen solely on the basis of MDCT and dissected directly. Exact
      correlation between surgical and radiological results was found in the first 36
      cases. A significant reduction in average operating time and postoperative
      complications was noted in the following 321 patients. CT angiogram provides
      important preoperative information on inferior abdominal wall vascular anatomy,
      facilitating DIEAP flap harvest, saving operative time, and reducing
      complications and costs. It proved to be an invaluable tool in the preoperative
      algorithm for DIEAP flap breast reconstruction.

PMID- 19742428
TI  - In vitro inhibition of platelet aggregation in response to increasing
      concentrations of tirofiban in patients with significant renal insufficiency.
AB  - BACKGROUND: Patients with impaired renal function are a growing subset at higher
      risk for cardiovascular complications due to vasculopathic state, inducing
      accelerated atherosclerosis and arteriosclerosis. These patients are at increased
      risk for complications after coronary interventions, especially major bleeding
      events. As a result, this at-risk population of patients has not been well
      studied in most of the major clinical trials evaluating coronary interventions.
      Of particular interest is the optimal dosing of glycoprotein IIb-IIIa inhibitors
      in the setting of acute myocardial infarction. In this study, we attempted to
      find the in vitro concentration of tirofiban required to inhibit platelet
      aggregation to <10% in patients with moderate to severe renal insufficiency.
      METHODS: A total of 21 patients were divided into two groups based on estimated
      creatinine clearance (group 1 <46ml/min; group 2 >46ml/min). Platelet-rich plasma
      from each subject was then incubated in vitro with increasing concentrations of
      tirofiban (25, 37.5, and 50ng/ml), and light transmission aggregometry assay was
      used to assess the degree of platelet aggregation in response to adenosine
      diphosphate (ADP). RESULTS: Patients in group 1 had a baseline platelet
      aggregation of 45%, which decreased to 10% at a 25.0ng/ml concentration of
      tirofiban; the effect was enhanced to a platelet aggregation of <5% at higher
      doses. In contrast, subjects in group 2 with creatinine clearance >or=46ml/min
      had an average platelet aggregation inhibition of 12% with 50ng/ml of
      tirofiban.We found a significant decrease in platelet aggregation in group 2 at
      25, 37.5, and 50ng/ml of tirofiban (p<0.05) in comparison with group 1.
      CONCLUSIONS: Our data indicate that patients with moderate to severe renal
      dysfunction suppress their platelet aggregation to <10% with 25ng/ml of
      tirofiban, one-third of the standard effective dose for patients with normal
      renal function.We suggest further clinical trials to define an objective means to
      calculate proper renal dosing of glycoprotein IIb-IIIa inhibitors in these
      patients to prevent potentially fatal complication of major hemorrhagic events.

PMID- 19742429
TI  - The Ohio State University Richard M Ross Heart Hospital--proof of concept--five
      years of growth and development.

PMID- 19742430
TI  - Reputational incentives--how improving transparency can drive hospital
      competition.

PMID- 19742431
TI  - Cardiogenic shock from left ventricular dysfunction complicating an acute ST
      elevation myocardial infarction.
AB  - Cardiogenic shock from left ventricular dysfunction complicating an acute ST
      elevation myocardial infarction is associated with high mortality. Much of the
      current understanding of the importance of emergency revascularization comes from
      the SHOCK trial. Mortality benefits combined with improved quality of life among
      the survivors justify the routine use of emergency revascularization in patients
      <75 years of age and in selected patients >or=75 years of age. This article
      discusses the SHOCK trial and potential mechanisms of benefit from
      revascularization as well as more recent information. Adjunctive therapies have
      been disappointing. To further improve outcomes, earlier pre-emptive and
      preventive strategies to ensure early revascularization should be pursued.

PMID- 19742432
TI  - Non-invasive risk stratification for implantable cardioverter-defibrillator
      placement--heart rate variability.
AB  - Heart rate variability (HRV) is a beat-to-beat variation in cardiac cycle length
      resulting from autonomic influence on the sinus node of patients in sinus rhythm.
      The importance of HRV as a risk stratifier has been well accepted, particularly
      in survivors of myocardial infarction. Large clinical trials are still needed to
      clarify the role of HRV in patients with non-ischemic cardiomyopathy. Given the
      significant association between HRV and the development of fatal
      arrhythmias/sudden cardiac death, HRV has been used in some clinical trials as
      one of the screening tests to select optimal candidates for implantable
      cardioverter-defibrillator placement, although its role in this area has not been
      fully established. Additional large prospective clinical trials are needed to
      further clarify the predictive value of existing or novel HRV parameters, on
      their own or in combination with other risk stratifiers, for assessing the risk
      of sudden cardiac death in a variety of clinical settings.

PMID- 19742433
TI  - Contrast-induced nephropathy-choice of contrast agents to reduce renal risk.
AB  - Contrast-induced nephropathy (CIN) represents an increasing healthcare burden and
      challenge as the frequency of diagnostic imaging and interventional procedures
      increases, particularly among patients at risk for developing CIN. Universally
      accepted strategies to reduce the risk for CIN include careful patient screening
      and selection, adequate patient hydration, limiting the volume of contrast medium
      administered, and choosing a safe, non-ionic, low-osmolar contrast agent. For
      both intra-arterial and intravenous use, all ionic and non-ionic iodinated
      contrast agents may further impair renal function in high-risk patients. Based on
      comparisons of contrast media in proximal renal tubular cell culture and in
      recent robust head-to-head prospective clinical trials in high-risk patients,
      however, iso-osmolar iodixanol and low-osmolar iopamidol are comparable and
      appear to be the contrast agents of choice to reduce renal risk for CIN.

PMID- 19742434
TI  - Antiplatelet resistance--fact or myth?

PMID- 19742435
TI  - Where's the beef? A case of left ventricular hypertrophy that isn't.

PMID- 19742436
TI  - Non-calcified coronary plaque in an asymptomatic physician.

PMID- 19742437
TI  - Advanced ('third-degree' or 'complete') interatrial block.

PMID- 19742438
TI  - Ventricular fibrillation as the presenting manifestation of adrenocortical
      carcinoma.
AB  - We describe a case of a young adult in whom sudden cardiac death due to
      ventricular fibrillation was the presenting manifestation of an adrenocortical
      carcinoma. The arrhythmia was precipitated by severe hypokalemia induced by the
      aldosterone-secreting tumor. Sudden death has not been previously described as a
      manifestation of this adrenal neoplasm. Unexplained persistent hypokalemia after
      resuscitated sudden death (especially when combined with hypertension( should
      prompt investigation for an underlying secondary hypertension, particularly
      adrenal pathology. Adrenocortical carcinoma should be considered in the
      differential diagnosis of unexplained sudden death associated with unexplained
      hypokalemia.

PMID- 19742439
TI  - Wide QRS complex supraventricular tachycardia with negative precordial
      concordance.
AB  - The authors describe the case of a 49-year-old man who experienced an episode of
      palpitations and dizziness. The results of 24-hour Holter monitoring demonstrated
      an episode of wide QRS complex regular tachycardia. During the
      electrophysiological study, a wide QRS complex tachycardia with negative
      precordial concordance was induced. A diagnosis of orthodromic atrioventricular
      re-entrant tachycardia involving a left lateral accessory pathway with left
      bundle branch aberration was made. This case represents a rare exception to the
      rule that negative precordial QRS concordance is diagnostic of ventricular
      tachycardia.

PMID- 19742440
TI  - A novel complication of bariatric surgery.
AB  - The incidence of obesity in the US is increasing. This has been associated with
      an increasing incidence and prevalence of diabetes, hypertension, and obstructive
      sleep apnea. Diet alone has generally been ineffective in attaining significant
      weight loss. Bariatric surgery is associated with significant weight loss and
      improvement in diabetes, hypertension, and obstructive sleep apnea. In this
      article we describe an unusual complication of bariatric surgery.

PMID- 19742441
TI  - The return of The American Heart Hospital Journal (AHHJ).

PMID- 19742442
TI  - Serum leptin levels in older patients with hip fracture--impact on peri-operative
      myocardial injury.
AB  - To evaluate whether there is a relationship between admission serum leptin
      concentrations and peri-operative myocardial injury, 238 consecutive older
      patients (mean age 81.9+/-7.9 years; 172 women) with low-trauma hip fracture were
      assessed. Myocardial injury as defined by elevated serum cardiac troponin I was
      associated with lower leptin levels analyzed as continuous or categorical
      variables. Patients with serum leptin concentrations <12ng/ml (medium value) had
      a two-fold greater increased risk for such complications compared with those with
      higher leptin levels (odd ratio 2.13, 95% confidence interval 1.06-4.28;
      p=0.033). This association remained significant after adjustments for age,
      gender, clinical (history of coronary artery disease [CAD], stroke, hypertension,
      diabetes, dementia), hematological (red, white, and lymphocyte count, hemoglobin,
      hematocrit), metabolic (parathyroid hormone [PTH], albumin), renal(creatinine,
      urea, glomerular filtration rate [GFR]), and inflammatory (C-reactive protein
      [CRP], ferritin) factors. The predictive value of lower leptin levels increased
      significantly when used in combination with traditional risk factors for
      myocardial injury.

PMID- 19742443
TI  - Comparative in vivo adulticidal activity of a topical dinotefuran versus an
      imidacloprid-based formulation against cat fleas (Ctenocephalides felis) on cats.
AB  - Fleas cause significant discomfort to pet cats and distress to their owners and
      are also vectors of disease severe infestations can cause anemia or flea allergy
      dermatitis and can lead to infections with Dipylidium caninum and Bartonella
      henselae. Rapid flea kill is an important feature of flea preventives. The
      efficacy of dinotefuran (Vectra for Cats and Kittens, Summit VetPharm) was
      compared with that of imidacloprid (Advantage, Bayer Animal Health) against
      Ctenocephalides felis when applied topically once on day 0. Cats were infested
      with 100 (+-3) C. felis on study days -1, 8, 15, 22, and 29. Live fleas were
      counted on study days 0 (2, 6, and 12 hours after treatment), 9, 16, 23, 29 (2,
      6, and 12 hours after infestation), and 30. Cats treated with dinotefuran had
      significantly (P less than .05) fewer fleas than the control cats at all
      posttreatment examinations except day 29 at 2 hours after infestation and
      significantly (P less than .05) fewel fleas than cats treated with imidacloprid
      on days 0 (2 hours after treatment), 9, 16, 23, 29 (6 and 12 hours after
      infestation), and 30.

PMID- 19742444
TI  - Efficacy of a topical ectoparasiticide containing dinotefuran, pyriproxyfen, and
      permethrin against Amblyomma americanum (Lone Star tick) and Amblyomma maculatum
      (Gulf Coast tick) on dogs.
AB  - Amblyomma americanum (lone star tick) and Amblyomma maculatum (Gulf Coast tick)
      are important disease vectors for both dogs and humans. This article describes
      two studies conducted to evaluate the efficacy of a new topical spot-on
      ectoparasiticide containing dinotefuran, permethrin, and pyriproxyfen (Vectra 3D,
      Summit VetPharm) against A. maculatum and A. americanum in dogs. Dogs were
      treated on day 0 and infested on days -1, 7, 14, 21, and 28 with approximately 40
      ticks each day. Live tick counts were determined 48 hours after infestation.
      Treatment with Vectra 3D resulted in a significant reduction in A. maculatum tick
      counts throughout the study period. For A. americanum, there was a significant
      reduction in tick counts from study day 9 onward. The results of this study
      indicate that Vectra 3D can be used as an effective part of an overall tick- and
      vector-borne disease control strategy on dogs when used monthly.

PMID- 19742445
TI  - Preliminary study of protamine zinc recombinant insulin for the treatment of
      diabetes mellitus in cats.
AB  - The efficacy of a new protamine zinc formulation based on recombinant insulin
      (PZIR) was compared with a veterinary-approved beef/pork-source insulin (PZI VET,
      Idexx Pharmaceuticals) that has been shown to significantly decrease blood
      glucose in cats with diabetes mellitus (DM). After being examined and weighed and
      having blood collected for determination of serum fructosamine concentrations, 50
      cats with DM and stable glycemic control on PZI VET were switched to PZIR for 30
      days at the same dose rate and interval. There was only one reported episode of
      hypoglycemia, and the cat was withdrawn from the study. In the 47 cats completing
      the study, there were no significant differences in body weight or serum
      fructosamine concentrations at days 15 or 30 compared with day 0. The results of
      this study indicate that PZIR provides glycemic control that is comparable to
      that of PZI VET when used at the same dose and dosing interval.

PMID- 19742446
TI  - Experimental reproduction of canine influenza virus H3N8 infection in young
      puppies.
AB  - Canine influenza virus (CIV) subtype H3N8 has emerged as a new pathogen with
      sustained transmission in the dog population in the United States. In this study,
      we report the experimental induction of respiratory disease in dogs using three
      CIV field isolates. Young (14 to 15 weeks of age) CIV-seronegative pups were
      challenged with one of three CIV isolates and monitored for clinical signs of
      respiratory disease, nasal virus shedding, seroconversion, lung lesions, and
      virus isolation from the lower respiratory tract. The challenged pups developed
      clinical signs and lung lesions typical of influenza virus infection, shed virus
      in their nasal secretions for 7 to 8 days after challenge, and exhibited serum
      antibodies at 7 and 14 days after challenge. Lung tissues and tracheal swabs
      collected at 3 and 6 days after challenge exhibited active virus replication.
      These results demonstrate that CIV causes respiratory disease in dogs.

PMID- 19742447
TI  - Evaluation of the potential for interaction between a metaflumizone-amitraz
      combination and dexmedetomidine hydrochloride in dogs.
AB  - This study investigated the effects on cardiovascular parameters, if any, of a
      commercially available combination of metaflumizone and amitraz administered to
      healthy, telemetered beagles that were subsequently sedated with dexmedetomidine.
      Dogs were sedated first without any pretreatment and then after pretreatment with
      metaflumizone and amitraz. Baseline values of all parameters were within normal
      limits for all dogs before the first anesthetic event. At 10 and 20 minutes after
      onset of sedation, oxygen saturation as measured by pulse oximetry was
      significantly higher for dogs that were pretreated with metaflumizone and
      amitraz. At all times after induction of sedation, blood pressure, heart rate,
      and baseline body temperature for dogs pretreated with metaflumizone and amitraz
      were not statistically different from when they were not pretreated. In
      conclusion, prior treatment with metaflumizone and amitraz did not influence the
      hemodynamic response to dexmedetomidine in telemetered dogs.

PMID- 19742448
TI  - Effect of a 1-hour IV infusion of doxorubicin on the development of
      cardiotoxicity in dogs as evaluated by electrocardiography and echocardiography.
AB  - Cardiotoxicity is a potentially life-threatening consequence of treatment with
      doxorubicin. Without reliable predictive or monitoring tests for early
      intervention, preventive methods are warranted. This study tested the hypothesis
      that a 1-hour infusion of doxorubicin would reduce the incidence of
      cardiotoxicity compared with historical incidences. Inclusion criteria for this
      retrospective trial were a minimum of three doses of doxorubicin administered as
      a 1-hour infusion in patients with at least two echocardiographic or
      electrocardiographic examinations during the course of treatment (median
      cumulative dose, 120 mg/m2). Of 133 dogs, 16 (12%) developed electrocardiographic
      abnormalities during or after treatment, which was statistically lower than the
      historical incidence of 17.7% (31 of 175 dogs). Only seven dogs (5.3%) developed
      abnormalities during the course of therapy. Three (2%) developed congestive heart
      failure.

PMID- 19742449
TI  - Use of a bioelectric impedance device in obese and lean healthy dogs to estimate
      body fat percentage.
AB  - A hand-held bioelectric impedance device was used to obtain body fat percentages
      from obese and lean healthy client-owned dogs. Bioelectric impedance values were
      compared with body condition scores assigned on a 9-point scale during physical
      examination to evaluate the correlation of these two methods for assessing body
      composition. A good correlation was revealed between body fat percentage as
      measured by the bioelectric impedance device and body condition score. The
      results of this study suggest that bioelectric impedance measurements of body fat
      percentage could be used by veterinary practitioners as an objective measure of
      adiposity when diagnosing and managing obese dogs.

PMID- 19742450
TI  - Efficacy of a combination of a fipronil-(S)-methoprene spot-on formulation and a
      deltamethrin-impregnated collar in controlling fleas and sandflies on dogs.
AB  - This study investigated the use of two commercial products, a deltamethrin
      impregnated collar and a fipronil-(S)-methoprene spot-on formulation, in
      combination to protect dogs against sandflies and fleas when they live in or
      travel to leishmaniasis-enzootic areas. Interactions, tolerance, and efficacy
      were evaluated. The combination was well tolerated by the six treated dogs. The
      antifeeding effect on Phlebotomus perniciosus ranged from 89.6% (day 1) to 99.51%
      (day 21) and exceeded 95% from day 7 through the end of the study; the mortality
      effect against P. perniciosus ranged from 87.52% (day 22) to 96.82% (day 15). The
      combination was 100% effective in controlling Ctenocephalides felis felis
      infestations for 36 days after treatment. These results suggest that it is
      feasible and advantageous to combine these two commercial products to protect
      dogs against sandflies and fleas in leishmaniasis-enzootic areas.

PMID- 19742451
TI  - A comparison of florfenicol-flunixin meglumine versus tulathromycin for the
      treatment of undifferentiated fever in fall-placed feedlot calves.
AB  - The purpose of this study was to compare the efficacy of a new combination drug,
      florfenicol-flunixin meglumine, with tulathromycin for initial treatment of
      undifferentiated fever (UF) in fall-placed calves that received metaphylactic
      tilmicosin on arrival at the feedlot. No significant differences were observed in
      UF relapses between the two drugs. Calves treated with florfenicol-flunixin had a
      lower crude case fatality rate (P = .0447) than calves treated with tulathromycin
      but did not have a significantly lower respiratory disease and histophilosis case
      fatality rate (P = .12). Whether the new florfenicol-flunixin product is more
      cost-effective than tulathromycin for the treatment of UF in fall-placed feedlot
      calves will depend on how the new product is priced in the marketplace relative
      to tulathromycin.

PMID- 19742452
TI  - Variation in the laboratory susceptibility of turf-infesting white grubs
      (Coleoptera: Scarabaeidae) to biological, biorational and chemical control
      products.
AB  - BACKGROUND: White grubs are the most widespread and damaging pests in turfgrass
      habitats of the northeast USA, and their management is highly dependent on
      chemical pesticides. Because this complex includes at least eight species,
      opportunities for pest management would be enhanced by understanding how
      susceptibility to control products varies across taxa. The objective of this
      laboratory study was to measure variation in the susceptibility of four species
      to 18 biological, biorational and chemical insecticides used as curative
      controls. RESULTS: Across species, the most efficacious biological and chemical
      insecticide alternatives were Steinernema scarabaei and chlorpyrifos
      respectively. For biorational and chemical insecticides, the European chafer
      [Amphimallon majale (Razoumowsky)] was the least susceptible species. For
      biologicals, the Japanese beetle (Popillia japonica Newman) was the least
      susceptible. Considering all control products, the oriental beetle [Anomala
      orientalis (Waterhouse)] was the most susceptible. CONCLUSION: The magnitude of
      variation in susceptibility supports the idea that a single product will not
      reliably suppress populations of all taxa, and highlights the need for pest
      management practitioners to identify white grub species before intervention. This
      differential susceptibility could have broader consequences for grub management
      if a numerically dominant target species is more completely suppressed than a co
      occurring species.

PMID- 19742744
TI  - Biochemical and histopathological effects of dietary oxidized cholesterol in
      rats.
AB  - Cholesterol oxidation products (COPs) have been associated with the genesis of
      chronic degenerative diseases, such as atherosclerosis. The purpose of this work
      was to study the histological changes by toxic effects of dietary COPs in liver
      and kidney. Five-week-old male Wistar albino rats were randomly divided into
      three groups of 10 rats each. Standard rat chow was supplemented with either 1%
      (w/w) pure cholesterol or 1% oxidized cholesterol and fed to the rats for 8
      weeks. Control animals were fed standard rat chow. At the end of the treatment
      period, the serum lipid profile was determined. The aorta, liver and kidneys were
      excised immediately, frozen with liquid nitrogen, and held at -70 degrees C. The
      histological study was carried out using conventional hematoxylin-eosin staining,
      and histochemical red oil 'O' was applied. COPs were analyzed by gas
      chromatography. Intake of dietary COPs altered biochemical parameters involved in
      lipid metabolism associated with atherogenesis in rats: total cholesterol,
      triacylglycerols and low density lipoproteins in serum. COPs detected in the
      liver and kidneys modified the organ original structure, caused an inflammatory
      process and promoted atherogenesis and atrophy of the tissue.

PMID- 19742777
TI  - Abstracts of 19th World Congress on Ultrasound in Obstetrics and Gynecology.
      September 13-17, 2009. Hamburg, Germany.

PMID- 19742782
TI  - Application of microwave-assisted extraction coupled with high-speed counter
      current chromatography for separation and purification of dehydrocavidine from
      Corydalis saxicola Bunting.
AB  - INTRODUCTION: Dehydrocavidine is a major component of Corydalis saxicola Bunting
      with sedative, analgesic, anticonvulsive and antibacterial activities.
      Conventional methods have disadvantages in extracting, separating and purifying
      dehydrocavidine from C. saxicola. Hence, an efficient method should be
      established. OBJECTIVE: To develop a suitable preparative method in order to
      isolate dehydrocavidine from a complex C. saxicola extract by preparative HSCCC.
      METHODOLOGY: The methanol extract of C. saxicola was prepared by optimised
      microwave-assisted extraction (MAE). The analytical HSCCC was used for the
      exploration of suitable solvent systems and the preparative HSCCC was used for
      larger scale separation and purification. Dehydrocavidine was analysed by high
      performance liquid chromatography (HPLC) and further identified by ESI-MS and 1H
      NMR. RESULTS: The optimised MAE experimental conditions were as follows:
      extraction temperature, 60 degrees C; ratio of liquid to solid, 20; extraction
      time, 15 min; and microwave power, 700 W. In less than 4 h, 42.1 mg of
      dehydrocavidine (98.9% purity) was obtained from 900 mg crude extract in a one
      step separation, using a two-phase solvent system composed of chloroform-methanol
      0.3 m hydrochloric acid (4 : 0.5 : 2, v/v/v). CONCLUSION: Microwave-assisted
      extraction coupled with high-speed counter-current chromatography is a powerful
      tool for extraction, separation and purification of dehydrocavidine from C.
      saxicola.

PMID- 19742859
TI  - Evaluation of aging influence on renal toxicity caused by segment-specific
      nephrotoxicants of the proximal tubule in rat.
AB  - Little is known concerning the sensitivity of aged rats to xenobiotics inducing
      kidney damage. To increase this knowledge, the age-dependent response of the
      kidney to hexachloro-1 : 3-butadiene (HCBD) or potassium dichromate (chromate)
      was investigated. Rats were treated at different ages with a single dose of
      segment-specific nephrotoxicants of the proximal tubule, chosen on the basis of
      their specificity for S(3) and for S(1)-S(2) segments, respectively. The
      toxicological impact of these xenobiotics has been evaluated through biochemical
      and genomic markers, and histopathological investigation of kidney samples. HCBD
      treatment induced tubular necrosis of the S(3) segment of the proximal tubule
      associated with changes of toxicological markers unrelated to the age. In
      contrast, chromate treatment induced an increased kidney damage related to the
      rat age. In fact, histopathological investigation revealed that at 1 month of age
      tubular vacuolar degeneration was seen affecting S(1)-S(2) segments of the
      proximal tubule, whereas at 3 months of age tubular necrosis occurred in the same
      segments associated with tubular dilation of the distal portions. Consistently,
      biochemical analysis confirmed a direct correlation among genomic and biochemical
      marker variability and animal age. Altogether, the results show that during aging
      there is an increased sensitivity of kidney to chromate but not to HCBD-induced
      damage and evidence differential age-related selectivity of rats for nephrotoxic
      compounds. Significance for human risk assessment is discussed.

PMID- 19743067
TI  - Analysis of metabolic variation and galanthamine content in Narcissus bulbs by 1H
      NMR.
AB  - INTRODUCTION: Galanthamine is a benzazepine alkaloid used as a drug to relieve
      symptoms of Alzheimer's disease. For pharmaceutical use this natural product has
      been extracted from the plant Leucojum aestivum (Amaryllidaceae) or produced
      synthetically. Limited supply of the natural source and high cost of synthetic
      production has led to a search for alternative sources of galanthamine. The bulbs
      of Narcissus pseudonarcissus (Amaryllidaceae) have been identified as a potential
      source of raw material for galanthamine extraction. Since inconsistent chemical
      composition can be an issue with medicinal plant material, it is of interest to
      know whether large variations occur between Narcissus bulbs grown in different
      geographical locations. OBJECTIVE: To evaluate whether large differences exist in
      the overall metabolic profiles of Narcissus bulbs grown in the two most important
      cultivation regions. METHODOLOGY: (1)H NMR and principal component analysis were
      used for an unbiased comparison of the bulb samples. RESULTS: Overall metabolite
      profiles were quite similar, but galanthamine levels could slightly discriminate
      samples by geographical region. (1)H NMR was used for quantitation of
      galanthamine, and was found to be comparable to quantitation by HPLC. Compared
      with conventional chromatographic methods, sample preparation for (1)H NMR
      analysis is simple and rapid, and only a small amount of plant material is
      required. CONCLUSIONS: Since useful qualitative and quantitative information
      about the metabolic state of Narcissus bulbs can be obtained by (1)H NMR, this
      method is useful for agricultural applications, and for quality control of raw
      material used in the pharmaceutical industry.

PMID- 19743068
TI  - Metabolomic analysis of Echinacea spp. by 1H nuclear magnetic resonance
      spectrometry and multivariate data analysis technique.
AB  - INTRODUCTION: The genus Echinacea (Asteraceae) comprises about 10 species
      originally distributed in North America. Three species are very well known as
      they are used worldwide as medicinal plants: Echinacea purpurea, E. pallida, E.
      angustifolia. OBJECTIVE: To discriminate between these three Echinacea species
      and E. simulata by (1)H NMR-based metabolomics. METHODOLOGY: (1)H NMR and
      multivariate analysis techniques were applied to diverse Echinacea plants
      including roots and aerial parts, authentic plants, commercial plants and
      commercial dry extracts. RESULTS: Using the (1)H NMR metabolomics, it was
      possible, without previous evaporation or separation steps, to obtain a metabolic
      fingerprint to distinguish between species. CONCLUSION: A clear distinction
      between the three pharmaceutical species was possible and some useful metabolites
      were identified.

PMID- 19743069
TI  - Mass spectrometry-based metabolomics oriented by correlation analysis for wound
      induced molecule discovery: identification of a novel jasmonate glucoside.
AB  - INTRODUCTION: Jasmonates are members of the oxylipin family involved in various
      plant regulatory processes, particularly in the response to biotic and abiotic
      stresses. They are present in very low amounts in wounded plants, which
      complicates their detection within complex plant extracts. Therefore, advanced
      analytical methods are needed for the profiling and characterisation of novel
      jasmonate derivatives. OBJECTIVE: To use metabolomics to search for original
      wound-induced metabolites belonging to the jasmonate family. METHODOLOGY:
      Numerous Arabidopsis specimens harvested at various time points after wounding
      were analysed by ultra-high pressure liquid chromatography coupled to time-of
      flight mass spectrometry (UHPLC/TOFMS). A correlation analysis based on kinetic
      profile similarities with known jasmonates was applied to find wound-induced
      molecules having a potential role in defence signalling. Their characterisation
      was performed by tandem mass spectrometry and capillary nuclear magnetic
      resonance spectroscopy. RESULTS: The statistical data treatment highlighted
      several previously reported jasmonates as well as a new glucoside derivative of
      the jasmonate 3-oxo-2-(2Z-pentenyl) cyclopentane-1-butyric acid (OPC-4). The
      monitoring of its kinetics in response to wounding revealed a delayed
      accumulation compared to the profile of OPC-4. This suggests an inactivation or
      elimination of OPC-4 through the formation of a polar glucosylated metabolite.
      CONCLUSION: The metabolomic approach developed has proved useful in the discovery
      of original jasmonates synthesised in response to plant wounding.

PMID- 19743070
TI  - Analysis of the monosaccharide composition of purified polysaccharides in
      Ganoderma atrum by capillary gas chromatography.
AB  - INTRODUCTION: Ganoderma, one of the best-known traditional Chinese medicines, has
      attracted considerable attention owing to the fact that dozens of polysaccharides
      isolated from it have shown diverse and potentially significant pharmacological
      activities. However, no work has been reported on the analysis of monosaccharide
      composition of polysaccharide isolated from the aqueous extract of Ganoderma
      atrum yet. OBJECTIVE: To develop a simple and sensitive GC-based method for the
      analysis of monosaccharide composition of purified polysaccharides in Ganoderma
      atrum. METHODOLOGY: The polysaccharide was first hydrolysed to give the
      constituent monosaccharides, which were subsequently derived into acetylated
      aldononitriles and analysed by gas chromatography using a capillary column packed
      with a (5%phenyl) methylpolysiloxane stationary phase with the addition of acetyl
      inositol as the inner standard. High-performance liquid chromatography was also
      used for comparison. RESULTS: The stable derivatives of the most common
      monosaccharides could be separated and reproducibly determined with high
      sensitivity. The limits of detection and quantification were 0.013 and 0.043
      mg/mL, respectively. The intermediary precision values (expressed as the RSD)
      were less than 10%. The mean recovery of the method was 100 + or - 3%, with RSD
      values of less than 5%. The results obtained from GC and HPLC methods were found
      to be close to each other within acceptable error ranges. CONCLUSION: This study
      demonstrated that the developed method could be applied as an accurate method for
      the compositional analysis of monosaccharides in the field of biological and
      biochemical study.

PMID- 19743189
TI  - Gene-environment interaction in posttraumatic stress disorder: an update.
AB  - The authors provide a detailed review of the extant gene-environment interaction
      (GxE) research in the etiology of posttraumatic stress disorder (PTSD). They
      begin with a discussion of why PTSD is uniquely fitting for the innovative
      framework of GxE methodology, followed by a review of the heritability and main
      effect molecular genetics studies of PTSD. Next, they discuss the six GxE
      investigations to date on PTSD. They end with a discussion of future directions
      and significance of this research, with an emphasis on the expansion of
      psychosocial factors that may be fitting environmental variables for inclusion in
      this new research area. The authors posit that GxE research is vital to
      elucidating risk and resilience following exposure to a potentially traumatic
      event.

PMID- 19743190
TI  - Genetic modification of the marine-derived yeast Yarrowia lipolytica with high
      protein content using a GPI-anchor-fusion expression system.
AB  - Yarrowia lipolytica SWJ-1b isolated from the marine fish gut was found to contain
      47.6 g of crude protein per 100 g of cell dry weight and had potential use as
      single cell protein. When the gene encoding enhanced green fluorescent protein
      (EGFP) was inserted into the surface display plasmid pINA1317-YlCWP110 and
      expressed in uracil mutant of Y. lipolytica SWJ-1b, the corresponding protein was
      successfully displayed on the cell surface, and 100% of the yeast cells exhibited
      the anchored target proteins. We found that yeast cells displaying EGFP were
      similar to those of Y. lipolytica SWJ-1b. Furthermore, C(18:1) and C(18:3) fatty
      acids biosynthesis in the marine yeast cells displaying the heterologous EGFP was
      weakly enhanced compared with that in its wild-type. The results suggest that the
      marine-derived Y. lipolytica SWJ-1b can be armed with the heterologous protein by
      the genetic modification and further used as single cell protein.

PMID- 19743227
TI  - Progesterone effects on subjective and physiological responses to intravenous
      nicotine in male and female smokers.
AB  - OBJECTIVE: Previous studies suggest possible modulatory effects of progesterone
      on nicotine addiction. The goal of this study was to determine the effects of
      progesterone, on acute physiological and subjective responses to intravenous (IV)
      nicotine in overnight abstinent male and female smokers. METHODS: Twelve smokers,
      six males and six females, participated in a double-blind, placebo-controlled,
      crossover study, which consisted of two experimental sessions. Before each
      session, subjects were treated orally with a single dose of either 200 mg
      progesterone or placebo. Starting 2 h following the medication treatment,
      subjects received an IV saline injection, followed by 0.5 and 1.0 mg/70 kg IV
      nicotine. RESULTS: Progesterone treatment, compared to placebo, enhanced the
      ratings of "bad effects," from IV nicotine and attenuated the rating of "drug
      liking." Progesterone also enhanced suppression of smoking urges by nicotine as
      assessed by the Brief Questionnaire on Smoking Urges (BQSU). CONCLUSIONS: These
      results suggest that progesterone may alter the subjective effects of nicotine as
      well as urges to smoke cigarettes. Further studies are warranted to examine the
      modulation of nicotine's effects by gonadal hormones.

PMID- 19743298
TI  - Physical activity and childhood cancer.
AB  - This review provides a survey of studies investigating physical activity and
      exercise interventions in patients during tumor treatment and survivors of
      childhood cancer. PubMed and Medline databases were searched using relevant
      terms. References of selected papers were tracked. A total of 28 studies could be
      identified. Seventeen studies investigated physical activity, 11 studies
      determined the effect of activity enhancing interventions during and after
      therapy. Even though most studies showed limitations and results were not
      consistent, considerably reduced physical activity is highly probable in patients
      during and after therapy. Studies on interventions provided promising results and
      revealed challenges to be faced.

PMID- 19743299
TI  - Health information needs of childhood cancer survivors and their family.
AB  - BACKGROUND: Knowledge about past disease, treatment, and possible late effects
      has previously been shown to be low in survivors of childhood cancer and their
      relatives. This study investigated the information needs of childhood cancer
      survivors and their parents and explored possible determinants for differences in
      information need and health-related Internet use. PROCEDURE: Childhood cancer
      survivors or their parents were contacted to complete a questionnaire about their
      characteristics, Internet use and requirements/expectations of a website on late
      effects (N = 160). RESULTS: One-hundred forty-five questionnaires (90.6%) were
      returned. Of the 69 respondents (49.3%) who had visited a late effects outpatient
      clinic prior to the survey, 20 (29.0%) had questions left after the consult. The
      large majority of the population had home access to Internet and 71 respondents
      (49.3%) used Internet for medical questions. Only 15 respondents (10.5%) used
      Internet to look for information on late effects of childhood cancer and only 4
      survivors found what they were looking for. Main information items requested were
      information about recognizing late effects, personalized information on late
      effects treatment and information on self-care. Only six respondents (4.2%)
      stated they would not visit a late effects website if it would be available.
      CONCLUSIONS: The need for late effects information showed to be of high priority
      by the majority of respondents, as was their interest in visiting a late effects
      website. In the development of a late effects website, attention should be given
      to patient information tailored to the personal situation of the website's users.

PMID- 19743300
TI  - Safety, efficacy, and pharmacokinetics of intravenous busulfan in children
      undergoing allogeneic hematopoietic stem cell transplantation.
AB  - PURPOSE: To determine the safety, efficacy, and PK profile of intravenous
      busulfan (Bu) in the context of a Bu and cyclophosphamide (IVBuCy) preparative
      regimen in children undergoing allogeneic hematopoietic stem cell transplantation
      (HSCT). METHODS: Twenty-four children were enrolled in an open-label, multicenter
      trial of IVBuCy as the preparative regimen for HLA-matched sibling allogeneic
      HSCT. IVBu was administered q6 hr for 16 doses with a targeted area under the
      curve (AUC) of 900-1,350 microMol-min. The initial dose was 0.8 mg/kg for
      children >4 years of age and 1 mg/kg for those <4 years of age. PK of the first
      dose IVBu was determined to calculate a single dosage adjustment, and with the
      9th and 13th doses to confirm steady-state PK. RESULTS: The targeted AUC was
      achieved with the first dose in 17/24 (71%) of the children using the age
      adjusted dosing approach. Dosing was increased in five patients, and reduced in
      two patients to achieve target values. After dose adjustment based on PK, 91% of
      the children had an AUC within the target range at steady state (AUCss). Median
      final dosing and clearance (CL) of IVBu were 1.1 mg/kg and 4.1 ml/min/kg in
      patients < or =4 years, and 0.9 mg/kg and 2.9 ml/min/kg in patients >4 years. All
      children were engrafted with documented donor chimerism. No late rejections or
      graft failures occurred. Four patients had veno-occlusive disease, three of which
      resolved within 2 weeks of onset. Two children died from transplant-related
      causes unrelated to Bu. CONCLUSION: IVBu is a safe and effective and offers the
      benefit of predictable and consistent systemic exposure.

PMID- 19743301
TI  - Massive response of severe infantile hepatic hemangioma to propanolol.

PMID- 19743302
TI  - Molecular genetic perspectives on the Indian social structure.
AB  - For historical reasons, the Indian subcontinent is endowed with enormous ethnic,
      cultural, and genetic heterogeneity of its people. In the process of
      understanding the dynamics and sociocultural complexity of Indian society,
      anthropologists have come up with a number of hypotheses involving certain
      social/cultural processes that may modulate evolutionary processes. In this
      article, we outline some of those hypotheses and present molecular genetic
      evidences, both published and unpublished, to demonstrate the effects of those
      social/cultural processes.

PMID- 19743303
TI  - Exercising some control over the hippocampus.

PMID- 19743304
TI  - Community acquired influenza requiring hospitalization: vaccine status is
      unrelated to morbidity in children with cancer.
AB  - BACKGROUND: Community acquired influenza can be severe and there are few data
      regarding hospitalization for children with cancer and influenza. Association
      between prior vaccination and infection severity has not been studied, although
      vaccination is standard practice. PROCEDURE: Patients with malignancy or prior
      stem cell transplant (SCT) were identified using a database of children with
      laboratory confirmed influenza (2000-2005). Other data collected included receipt
      of vaccine, absolute neutrophil count (ANC) and absolute lymphocyte count (ALC).
      These were compared with intensive care unit (ICU) stay, respiratory
      complications and hospital days. RESULTS: There were 39 patients with laboratory
      confirmed influenza with a median age of 6.9 years. Twenty-four (62%) were on
      cancer therapy at time of infection and 18 (46%) had received the influenza
      vaccination that season. Measures of immune status included ANC at time of
      infection (median 1,530 cells/microl; inter-quartile range, 315, 4347), presence
      of graft versus host disease 2 (5%) and steroid therapy 4 (10%) patients. All had
      a low ALC (median 448 cells/microl; IQR 189, 861). Respiratory complications
      occurred in 8 (20%), ICU admissions in 4 (10%) and death in 2 (5%) patients.
      Median hospital stay was 2 days. All ICU admissions occurred in unvaccinated
      patients (P = 0.1). Vaccine status, ANC (<1,000 cells/microl vs. >1,000) and ALC
      (<500 cells/microl vs. >500) were not associated with length of stay or
      respiratory complications. CONCLUSIONS: Influenza infection can be severe in
      children with cancer and complications occur despite vaccination. Prospective
      evaluation of vaccine response is worthy of future study.

PMID- 19743305
TI  - Human population genetic diversity as a function of SNP type from HapMap data.
AB  - Data from the international HapMap project were mined to determine if the degree
      of genetic differentiation (Fst) is dependent on single nucleotide polymorphism
      (SNP) category. The Fst statistic was evaluated across all SNPs for each of 30
      genes and for each of five chromosomes. A consistent decrease in diversity
      between Europeans and Africans was seen for nonsynonymous coding region SNPs
      compared to the three other SNP categories: synonymous SNPs, UTR, and intronic
      SNPs. This suggests an effect of balancing selection in reducing interpopulation
      genetic diversity at sites that would be expected to influence phenotype and
      therefore be subject to selection. This result is inconsistent with the concept
      of large population specific genetic differences that could have applications in
      "racialized medicine."

PMID- 19743388
TI  - Fluoride-induced changes in haem biosynthesis pathway, neurological variables and
      tissue histopathology of rats.
AB  - This study intended to determine the effects of various concentrations of
      fluoride (1, 10, 50 and 100 ppm) in drinking water for a period of 12 weeks on
      changes in haem biosynthesis pathway, oxidative stress and neurological variables
      supported by histopathological observations and fluoride in rats. The data
      indicates significant alterations in the parameters related to haeme synthesis
      pathway like inhibition of blood delta-aminolevulinic acid dehydratase, delta
      aminolevulinic acid synthetase, oxidative stress like depletion of glutathione
      (GSH) and increase in oxidized glutathione (GSSG) and thiobarbituric acid
      reactive substances. These changes were accompanied by depletion in GSH:GSSG
      ratio, whole brain biogenic amine levels and a dose-dependent increase in
      fluoride concentration. Interestingly and most significantly, these changes were
      more pronounced at lower concentrations of fluoride compared with higher fluoride
      dose. Biochemical changes were supported by the histological observations, which
      also revealed that at high concentrations of fluoride, toxic effects and damages
      to organs were more pronounced. These changes support our earlier findings
      regarding the role of decreased ionic mobility of fluoride ion at higher
      concentrations, leading to less pronounced toxicity.

PMID- 19743389
TI  - Approach to estimation of absorption of aliphatic hydrocarbons diffusing from
      interior materials in an automobile cabin by inhalation toxicokinetic analysis in
      rats.
AB  - The interior air of an automobile cabin has been demonstrated in our previous
      studies to be contaminated by high concentrations of a large variety of aliphatic
      hydrocarbons diffusing from the interior materials. In the present study, the
      amounts of seven selected aliphatic hydrocarbons absorbed by the car driver were
      estimated by evaluating their inhalation toxicokinetics in rats. Measured amounts
      of the substances were injected into a closed chamber system in which a rat had
      been placed, and the concentration changes in the chamber were examined. The
      toxicokinetics of the substances were evaluated based on concentration-time
      courses using a nonlinear compartment model. Their absorption amounts in humans
      at the levels of actual concentrations in the cabins without ventilation were
      extrapolated from the results found with the rats. The absorption amounts
      estimated for a driver during a 2 h drive were as follows: 6 microg/60 kg of
      human body weight for methylcyclopentane (interior concentration 23 microg/m(3)
      as median value in previous study), 5 microg for 2-methylpentane (36
      microg/m(3)), 13 microg for n-hexane (65 microg/m(3)), 51 microg for n-heptane
      (150 microg/m(3)), 26 microg for 2,4-dimethylheptane (97 microg/m(3)), 17 microg
      for n-nonane (25 microg/m(3)) and 49 microg for n-decane (68 microg/m(3)). An
      inverse relationship was found between the exposure and absorption among the
      substances (e.g. between n-decane and 2,4-dimethylheptane). These findings
      suggest that not only the exposure concentrations but also the absorption amounts
      should be taken into account to evaluate the health effects of exposure to low
      concentrations of volatile compounds as environmental contaminants.

PMID- 19743393
TI  - Long-term exposure to bis(2-ethylhexyl)phthalate (DEHP) inhibits growth of guppy
      fish (Poecilia reticulata).
AB  - Bis(2-ethylhexyl)phthalate (DEHP) is a widely used plasticizer that is a commonly
      found contaminant of aquatic environments. However, little is known about the
      long-term effects of DEHP on fish development, as previous studies yielded
      conflicting results and mostly investigated the effects of concentrations higher
      than those found in natural habitats. We thus aimed to investigate the effects of
      DHEP (i) at concentrations present in the environment, and (ii) under conditions
      that might accentuate any deleterious consequences (larvae rather than adult
      fish, use of higher temperature). Different concentrations of DEHP (0.1-10 microg
      l(-1)rpar; applied continuously for 91 days were tested on guppy fish that were
      less than one week old at the beginning of the treatment. As early as 14 days
      after the start of exposure, guppies treated with 10 microg l(-1) DEHP showed
      significantly reduced body length as compared with control fish. The inhibitory
      effect of DEHP was concentration-dependent and increased with time, leading to a
      maximal reduction in body length of 15 and 40% at 1 and 10 microg l(-1) DEHP,
      respectively. The effect was even more pronounced for body weight, which was
      diminished by up to 40 and 70% at 1 and 10 microg l(-1) DEHP, respectively. The
      reduction in growth was still significant at 91 days of DEHP treatment, whereas
      the Fulton's condition factor was unaffected. While DEHP significantly blocked
      growth in both male and female guppies, no shift in the sexual development was
      observed. These data show that DEHP, at concentrations present in aquatic
      environments, can profoundly affect development in fish.

PMID- 19743401
TI  - Evolving understanding of the evolution of herbicide resistance.
AB  - A greater number of, and more varied, modes of resistance have evolved in weeds
      than in other pests because the usage of herbicides is far more extensive than
      the usage of other pesticides, and because weed seed output is so great. The
      discovery and development of selective herbicides are more problematic than those
      of insecticides and fungicides, as these must only differentiate between plant
      and insect or pathogen. Herbicides are typically selective between plants,
      meaning that before deployment there are already some crops possessing natural
      herbicide resistance that weeds could evolve. The concepts of the evolution of
      resistance and the mechanisms of delaying resistance have evolved as nature has
      continually evolved new types of resistance. Major gene target-site mutations
      were the first types to evolve, with initial consideration devoted mainly to
      them, but slowly 'creeping' resistance, gradually accruing increasing levels of
      resistance, has become a major force owing to an incremental accumulation of
      genetic changes in weed populations. Weeds have evolved mechanisms unknown even
      in antibiotic as well as other drug and pesticide resistances. It is even
      possible that cases of epigenetic 'remembered' resistances may have appeared.

PMID- 19743394
TI  - Adjunctive use of lithium carbonate for the management of neutropenia in
      clozapine-treated children.
AB  - OBJECTIVE: Clozapine, a dibenzodiazepine antipsychotic, is the most effective
      medication for treatment-resistant schizophrenia. However, its use has been
      limited by the high risk of neutropenia. In children, the rate of neutropenia is
      higher when compared to adults. We decided to explore the use of lithium to
      manage neutropenia in childhood-onset schizophrenia (COS) through a systematic
      audit of COS cases. METHODS: Medical records were reviewed for patients with COS
      who had been treated with the combination of clozapine and lithium carbonate.
      RESULTS: Seven patients were found to have been treated with both clozapine and
      lithium. After initiation of lithium, ANC increased significantly in six out of
      seven subjects by 29 to 106% with a mean of 66%. In addition, six out of seven
      subjects continued using both clozapine and lithium for over 2 years (range: 2.0
      7.2 years) and do not have immediate plans for discontinuation of either
      medications. CONCLUSIONS: Our study bolsters support for the use of lithium in
      the management of neutropenia in children treated with clozapine. Although the
      coadministration of lithium and clozapine appears effective in the management of
      neutropenia, it is not without its risks and clinicians must be diligent in their
      joint use of these medications.

PMID- 19743405
TI  - Cellular DNA breakage by soy isoflavone genistein and its methylated structural
      analogue biochanin A.
AB  - Epidemiological studies have indicated that populations with high isoflavone
      intake through soy consumption have lower rates of breast, prostate, and colon
      cancer. The isoflavone polyphenol genistein in soybean is considered to be a
      potent chemopreventive agent against cancer. In order to explore the chemical
      basis of chemopreventive activity of genistein, in this paper we have examined
      the structure-activity relationship between genistein and its structural analogue
      biochanin A. We show that both genistein and its methylated derivative biochanin
      A are able to mobilize nuclear copper in human lymphocyte, leading to degradation
      of cellular DNA. However, the relative rate of DNA breakage was greater in the
      case of genistein. Further, the cellular DNA degradation was inhibited by copper
      chelator (neocuproine/bathocuproine) but not by compounds that specifically bind
      iron and zinc (desferrioxamine mesylate and histidine, respectively). We also
      compared the antioxidant activity of the two isoflavones against tert
      butylhydroperoxide-induced oxidative breakage in lymphocytes. Again genistein was
      found to be more effective than biochanin A in providing protection against
      oxidative stress induced by tert-butylhydroperoxide. It would therefore appear
      that the structural features of isoflavones that are important for antioxidant
      properties are also the ones that contribute to their pro-oxidant action through
      a mechanism that involves redox cycling of chromatin-bound nuclear copper.

PMID- 19743406
TI  - Differential inhibitory effects of inotilone on inflammatory mediators, inducible
      nitric oxide synthase and cyclooxygenase-2, in LPS-stimulated murine macrophage.
AB  - The inhibitory effects of inotilone and methylinotilone on the induction of
      inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in murine RAW
      264.7 cells activated with LPS were investigated. The results show that both
      hydroxyl groups on the benzene ring of the inotilone molecule are required for
      better anti-inflammatory effect. Western blotting and RT-PCR analyses
      demonstrated that inotilone blocked protein and mRNA expression of iNOS but not
      COX-2. Instead, inotilone inhibited prostaglandin E(2) production through
      decreasing the enzyme activity of COX-2. The repression of iNOS but not COX-2
      expression may come from the differential effect of inotilone on nuclear factor
      kappaB (NFkappaB) and CCAAT/enhancer-binding protein beta Treatment with
      inotilone resulted in the reduction of LPS-induced nuclear translocation of
      NFkappaB subunit and the NFkappaB-dependent transcriptional activity by blocking
      phosphorylation of inhibitor kappaB(IkappaB)alpha and p65 and subsequent
      degradation of inhibitor kappaBalpha. Inotilone also inhibited LPS-induced
      activation of PI3K/Akt and extracellular signal-regulated kinase 1/2 and p38
      mitogen-activated protein kinase. Our results suggest that inotilone may have
      potential to be developed into an effective anti-inflammatory agent.

PMID- 19743407
TI  - Purified berry anthocyanins but not whole berries normalize lipid parameters in
      mice fed an obesogenic high fat diet.
AB  - Male C57BL/6 mice received diets with either 10% of kcal from fat, or a high fat
      diet [45% (HF45) or 60% (HF60) kcal from fat]. Diets were prepared with or
      without freeze-dried powders (10%) from whole blueberries (BB), strawberries
      (SB), Concord grape or black raspberry. In the 2nd study, purified anthocyanins
      (ACNs) from SB or BB were added to the drinking water of the treatments fed the
      HF60 diet. In Study 1, serum triglycerides were increased by feeding the HF45
      diet but were elevated further when black raspberry or BB was included in the
      HF45 diet. Liver total lipids and triglycerides were increased in mice fed HF45
      diet and inclusion of any of the berry powders in the HF45 diet did not alter
      concentrations compared to HF45 controls. In the 2nd study, mice fed the HF60
      diet plus purified ACNs from BB in the water had lower body weight gains and body
      fat than the HF60 fed. Serum cholesterol and triglyceride levels were elevated
      with the HF60 diet and decreased to control levels when ACNs from either SB or BB
      were included in the drinking water. Serum leptin levels were consistently
      decreased to control low fat levels in those ACN treatments in which measures of
      body fat were decreased. Administering purified ACNs from BB and strawberry via
      drinking water prevented the development of dyslipidemia and obesity in mice, but
      feeding diets containing whole berries or purple corn (PC) ACNs did not alter the
      development of obesity.

PMID- 19743408
TI  - Fluorescence-based quantitative scratch wound healing assay demonstrating the
      role of MAPKAPK-2/3 in fibroblast migration.
AB  - The scratch wound healing assay is a sensitive method to characterize cell
      proliferation and migration, but it is difficult to be quantitatively evaluated.
      Therefore, we developed an infrared fluorescence detection-based real-time assay
      for sensitive and accurate quantification of cell migration in vitro. The method
      offers sensitivity, simplicity, and the potential for integration into automated
      large-scale screening studies. A live cell staining lipophilic tracer-1,1'
      dioctadecyl-3,3,3',3'-tetramethyl indotricarbocyanine iodide (DiR)-is used for
      accurate imaging of wound closure in a simple 96-well scratch assay. Scratches
      are made on prestained confluent cell monolayers using a pipette tip and scanned
      at different time intervals using a fluorescent scanner. Images are analyzed
      using Image J software and the migration index is calculated. Effect of cell
      number, time after scratch and software settings are analyzed. The method is
      validated by showing concentration- and time-dependent effects of cytochalasin-D
      on fibroblast migration. Using this assay, we quantitatively evaluate the role of
      the MAPK-activated protein kinases MK2 and MK3 in fibroblast migration. First,
      the migratory phenotype of MK2-deficient MEFs is analyzed in a retroviral rescue
      model. In addition, migration of MK2/3-double-deficient cells is determined and
      the ability of MK3 to rescue cell migration in MK2/3-double-deficient fibroblasts
      is demonstrated.

PMID- 19743409
TI  - Automatic testing and assessment of neuroanatomy using a digital brain atlas:
      method and development of computer- and mobile-based applications.
AB  - Preparation of tests and student's assessment by the instructor are time
      consuming. We address these two tasks in neuroanatomy education by employing a
      digital media application with a three-dimensional (3D), interactive, fully
      segmented, and labeled brain atlas. The anatomical and vascular models in the
      atlas are linked to Terminologia Anatomica. Because the cerebral models are fully
      segmented and labeled, our approach enables automatic and random atlas-derived
      generation of questions to test location and naming of cerebral structures. This
      is done in four steps: test individualization by the instructor, test taking by
      the students at their convenience, automatic student assessment by the
      application, and communication of the individual assessment to the instructor. A
      computer-based application with an interactive 3D atlas and a preliminary mobile
      based application were developed to realize this approach. The application works
      in two test modes: instructor and student. In the instructor mode, the instructor
      customizes the test by setting the scope of testing and student performance
      criteria, which takes a few seconds. In the student mode, the student is tested
      and automatically assessed. Self-testing is also feasible at any time and pace.
      Our approach is automatic both with respect to test generation and student
      assessment. It is also objective, rapid, and customizable. We believe that this
      approach is novel from computer-based, mobile-based, and atlas-assisted
      standpoints.

PMID- 19743410
TI  - Quantitative and qualitative changes in teaching histology by means of virtual
      microscopy in an introductory course in human anatomy.
AB  - This study compares overall laboratory averages and individual test scores along
      with a student survey to determine the effects of using virtual microscopy in
      place of optical microscopes in a large undergraduate human anatomy course. T
      tests revealed that the first two laboratory examinations (of four) and the
      overall laboratory averages were significantly increased compared with the
      previous year. We hypothesize that this is due to students' ability to use and
      understand the technology quickly as opposed to learning how to maneuver an
      optical microscope. Students also responded positively in a survey about the
      virtual microscope, indicating that increased accessibility, ease of use, and the
      ability to understand the material were important components of the virtual
      microscope. In addition, an increase in student collaboration was noted because
      multiple students were able to view the image at a time. This level of acceptance
      of virtual microscopy has been reported in previous studies, though this level of
      increased examination scores is rare. We attribute this to differences between
      the medical students, with whom this technology has been researched in the past,
      and undergraduate introductory students.

PMID- 19743411
TI  - Proteomic, functional and motif-based analysis of C-terminal Src kinase
      interacting proteins.
AB  - C-terminal Src kinase (Csk) that functions as an essential negative regulator of
      Src family tyrosine kinases (SFKs) interacts with tyrosine-phosphorylated
      molecules through its Src homology 2 (SH2) domain, allowing it targeting to the
      sites of SFKs and concomitantly enhancing its kinase activity. Identification of
      additional Csk-interacting proteins is expected to reveal potential signaling
      targets and previously undescribed functions of Csk. In this study, using a
      direct proteomic approach, we identified 151 novel potential Csk-binding
      partners, which are associated with a wide range of biological functions.
      Bioinformatics analysis showed that the majority of identified proteins contain
      one or several Csk-SH2 domain-binding motifs, indicating a potentially direct
      interaction with Csk. The interactions of Csk with four proteins (partitioning
      defective 3 (Par3), DDR1, SYK and protein kinase C iota) were confirmed using
      biochemical approaches and phosphotyrosine 1127 of Par3 C-terminus was proved to
      directly bind to Csk-SH2 domain, which was consistent with predictions from in
      silico analysis. Finally, immunofluorescence experiments revealed co-localization
      of Csk with Par3 in tight junction (TJ) in a tyrosine phosphorylation-dependent
      manner and overexpression of Csk, but not its SH2-domain mutant lacking binding
      to phosphotyrosine, promoted the TJ assembly in Madin-Darby canine kidney cells,
      implying the involvement of Csk-SH2 domain in regulating cellular TJs. In
      conclusion, the newly identified potential interacting partners of Csk provided
      new insights into its functional diversity in regulation of numerous cellular
      events, in addition to controlling the SFK activity.

PMID- 19743412
TI  - Identification of a NCR+/NKG2D+/LFA-1(low)/CD94(-) immature human NK cell subset.
AB  - CD56(bright) natural killer (NK) cells, generated in vitro from CD34+
      hematopoietic progenitor cells, were characterized after a 30-day culture with
      flt3 ligand plus IL-15. Virtually, all CD56(bright) cells expressed CD117, CD25,
      natural cytotoxicity receptors (NCRs), NKG2D, CD161, and CD244, while only a
      subset expressed CD18-CD11a (LFA-1), and CD94 molecule, defining an immature
      CD56(bright)/NCRs+/NKG2D+/LFA-1(-)/CD94(-) subset. Another small subset of cells
      expressing CD94 but not LFA-1 integrin was also identified, suggesting that
      during NK differentiation LFA-1 might be upregulated later than CD94. To verify
      this hypothesis in vivo, we evaluated the NK cell expression of LFA-1 in both
      peripheral and umbilical cord blood samples. Interestingly, in these blood
      fluids, we have identified a lineage negative CD34(-)/LFA
      1(low)/NKp46(dim)/NKG2D(dim)/CD94(-) subset that resembled an immature stage of
      NK cells present in lymph nodes. Altogether, the results indicate that CD18-CD11a
      integrin, as well as CD11b in mice, may be a useful marker to identify immature
      stages of NK cell differentiation.

PMID- 19743413
TI  - The identification and enumeration of dendritic cell populations from individual
      mouse spleen and Peyer's patches using flow cytometric analysis.
AB  - Dendritic cell (DC) research currently involves pooling of tissues from multiple
      animals followed by enrichment techniques to obtain sufficient numbers of DCs for
      analysis. Enrichment techniques take advantage of DC adherence, buoyant density
      properties, and/or positive or negative selection of cell populations using
      monoclonal antibodies. However, enrichment techniques may significantly change
      the maturation and/or activation status of DCs or selectively eliminate one or
      more subpopulations of DCs. To overcome these drawbacks, we designed a multicolor
      flow cytometric technique for simultaneous analysis of DC populations from
      tissues of individual mice. The spleens and Peyer's patches were mechanically and
      enzymatically digested, then incubated with a panel of six monoclonal antibody
      fluorochrome direct conjugate reagents. A BD(R) Biosciences LSR II flow cytometer
      and FCS Express(R) software were used to identify three subtypes of mature DCs
      (myeloid, lymphoid, and plasmacytoid), precursor DCs, polymorphonuclear
      neutrophils, B lymphocytes, and Gr-1(+)/CD8alpha(+) memory T lymphocytes in the
      spleen. Likewise, we also identified these DC subpopulations and B lymphocytes in
      the Peyer's patches. The three key parameters in analysis of the DC populations
      were bi-exponential plotting in data analysis, collection of a minimum of 50,000
      total events, and accurate color compensation. This procedure to analyze DCs from
      individual mice can lead to further understanding of the role of DCs in many
      other model systems as well as better understanding of how dietary or
      physiological factors may affect in vivo DC homeostasis.

PMID- 19743414
TI  - Shotgun proteome profile of Populus developing xylem.
AB  - Understanding the molecular pathways of plant cell wall biosynthesis and
      remodeling is central to interpreting biological mechanisms underlying plant
      growth and adaptation as well as leveraging that knowledge towards development of
      improved bioenergy feedstocks. Here, we report the application of shotgun MS/MS
      profiling to the proteome of Populus developing xylem. Nearly 6000 different
      proteins were identified from the xylem proteome. To identify low-abundance DNA
      regulatory proteins from the developing xylem, a selective nuclear proteome
      profiling method was developed. Several putative transcription factors and
      chromatin remodeling proteins were identified using this method, such as NAC
      domain, CtCP-like and CHB3-SWI/SNF-related proteins. Public databases were mined
      to obtain information in support of subcellular localization, transcript-level
      expression and functional categorization of identified proteins. In addition to
      finding protein-level evidence of candidate cell wall biosynthesis genes from
      xylem (wood) tissue such as cellulose synthase, sucrose synthase and
      polygalacturonase, several other potentially new candidate genes in the cell wall
      biosynthesis pathway were discovered. Further application of such proteomics
      methods will aid in plant systems biology modeling efforts by enhancing the
      understanding not only of cell wall biosynthesis but also of other plant
      developmental and physiological pathways.

PMID- 19743415
TI  - Nanozeolite-driven approach for enrichment of secretory proteins in human
      hepatocellular carcinoma cells.
AB  - Given the importance of secreted proteins as a source for early detection and
      diagnosis of disease, secreted proteins have been arousing considerable
      attention. However, the analysis of secreted proteins represents a challenge for
      current proteomic techniques. One of the difficulties in secretomic study is to
      concentrate proteins from large volume of growth media, particularly, the low
      abundant and low molecular weight proteins (molecular weight <30 kDa). Herein, we
      describe a novel strategy for harvesting secretory proteins. In this approach,
      proteins secreted from the human hepatocellular carcinoma cell line were enriched
      by zeolite LTL nanocrystals, followed by 1-D SDS-PAGE for protein fractionation
      and then by LC-ESI-MS/MS for protein identification. In total, 1474 unique
      proteins were confidently identified, including 505 low molecular weight
      proteins, and covered a broad range of pI and molecular weight. Furthermore, this
      study not only offered an efficient and powerful method for the enrichment of
      secretory proteins but also allowed in-depth study of secretome of hepatocellular
      carcinoma cells. The reported work is expected to represent one of the most
      comprehensive secretomic analyses so far.

PMID- 19743416
TI  - The effect of carbon source on the secretome of Kluyveromyces lactis.
AB  - A proteomic analysis was performed on spent fermentation medium following
      bioreactor propagation of a wild-type industrial strain to identify proteins
      naturally secreted by Kluyveromyces lactis cells. Here, we report changes
      detected in the K. lactis secretome as a result of growth in three different
      carbon sources: glucose, galactose and glycerol. A total of 151 secreted proteins
      were detected by multi-dimensional separations and reversed-phase online nanoESI
      MS/MS analysis. From these, we were able to identify 63 proteins (termed the
      "base secretome") that were common to all three fermentation conditions. The
      majority of base secretome proteins, 79%, possessed general secretory pathway
      (GSP) sequences and were involved with cell wall structure, glycosylation,
      carbohydrate metabolism and proteolysis. There was little variation in the
      functional groupings of base secretome GSP proteins and GSP proteins that were
      not part of the base secretome. In contrast, the majority of non-GSP proteins
      detected were not part of the base secretome and the functions of these proteins
      varied significantly. Finally, through further identification of non-GSP proteins
      in carbon sources not originally tested, we have gained further evidence of a
      protein export mechanism separate from the GSP in K. lactis.

PMID- 19743417
TI  - Diminished expression of dihydropteridine reductase is a potent biomarker for
      hypertensive vessels.
AB  - To identify the new targets for hypertension, we analyzed the protein expression
      profiles of aortic smooth muscle in spontaneously hypertensive rats (SHR) of
      various ages during the development of hypertension, as well as in age-matched
      normotensive Wistar-Kyoto (WKY) rats, using a proteomic analysis. The expressions
      of seven proteins were altered in SHR compared with WKY rats. Of these proteins,
      NADH dehydrogenase 1alpha, GSTomega1, peroxi-redoxin I and transgelin were
      upregulated in SHR compared with WKY rats. On the other hand, the expression of
      HSP27 and Ran protein decreased in SHR. The diminution of dihydrobiopterin
      reductase, an enzyme located in the regeneration pathways of tetrahydrobiopterin
      (BH4), was also prominent in SHR. The results from a PCR analysis revealed that
      the expression of BH4 biosynthesis enzymes - GTP cyclohydrolase-1 and sepiapterin
      reductase - decreased and increased, respectively, in SHR compared with WKY rats.
      The level of BH4 was less in aortic strips from SHR than from WKY rats. Moreover,
      treatment with BH4 inhibited aortic smooth muscle contraction induced by
      serotonin. These results suggest that the deficiency in BH4 regeneration produced
      by diminished dihydrobiopterin reductase expression is involved in vascular
      disorders in hypertensive rats.

PMID- 19743418
TI  - Proteomic study of DBA/2J mice retina: Down-regulation of Integrin beta7
      correlated with retinal ganglion cell death.
AB  - To identify and determine the function of the proteins associated with the death
      of retinal ganglion cells (RGCs) in DBA/2J mice, an animal model of glaucoma,
      retinas of DBA/2J mice, were analyzed by proteomics at 5-, 7-, and 11-months-of
      age. The proteins showing significant alterations were selected for
      identification by MS and 18 proteins were differentially expressed and the
      identified proteins included cell membrane receptors and proteins associated with
      intracellular signaling pathways. Among of identified proteins, the expression of
      Integrin beta7 at 7-months-of-age was decreased by about 89% of that at 5-months
      of-age. Integrin beta7 was expressed in the RGCs. The effect of glutamate
      toxicity on the expression pattern of Integrin beta7 in a RGC line was also
      investigated and the glutamate-induced death of RGC was inhibited by the RNA
      knockdown of Integrin beta7. Our data showed also that the expression of 18
      proteins in the DBA/2J was significantly altered in DBA2 mice and down-regulation
      of Integrin beta7 may have a protective effect on glutamate-induced death of
      RGCs.

PMID- 19743419
TI  - Proteopathogen, a protein database for studying Candida albicans--host
      interaction.
AB  - There exist, at present, public web repositories for management and storage of
      proteomic data and also fungi-specific databases. None of them, however, is
      focused to the specific research area of fungal pathogens and their interactions
      with the host, and contains proteomics experimental data. In this context, we
      present Proteopathogen, a database intended to compile proteomics experimental
      data and to facilitate storage and access to a range of data which spans
      proteomics workflows from description of the experimental approaches leading to
      sample preparation to MS settings and peptides supporting protein identification.
      Proteopathogen is currently focused on Candida albicans and its interaction with
      macrophages; however, data from experiments concerning different pathogenic fungi
      species and other mammalian cells may also be found suitable for inclusion into
      the database. Proteopathogen is publicly available at
      http://proteopathogen.dacya.ucm.es.

PMID- 19743420
TI  - The properties of hub proteins in a yeast-aggregated cell cycle network and its
      phase sub-networks.
AB  - Currently, most researches on the properties of interacting proteins, hubs in
      particular, are mainly based on an aggregated network of binary interactions.
      Here, by projecting a yeast-aggregated cell cycle network into four phase (G1, S,
      G2 and M) sub-networks, we explored the properties of the hubs of the aggregated
      network. We found, as expected that only 69% (103 of 149) of hubs still act as
      hubs in at least one of the four sub-networks. Interestingly, those (19%) that
      are not hubs in any phase tend to perform multiple functions and differ from the
      others in their network positions. We also analyzed the potential biological
      features among the dynamic and static hubs. Finally, we investigated the dynamic
      properties of two complexes, the anaphase-promoting complex and the chromatin
      remodeling complex. The dynamic function of the anaphase-promoting complex is
      represented by its interactions with CDC28 at different stages of mitotic cell
      cycle. The chromatin-remodeling complex is assembled when its dynamic component,
      ARP7, is periodically expressed in S phase to function in chromatin remodeling,
      which could reflect the just-in-time assembly of protein complexes. In
      conclusion, the study of decomposing the aggregated network and characterizing
      the hubs in decomposed sub-networks is useful for further understanding the
      dynamic functions of yeast cell cycle.

PMID- 19743421
TI  - Inoculation-density-dependent responses and pathway shifts in Saccharomyces
      cerevisiae.
AB  - The cell-density-dependent responses of Saccharomyces cerevisiae to inoculation
      sizes were explored by a proteomic approach. According to their gene ontology,
      100 protein spots with differential expression, corresponding to 67 proteins,
      were identified and classed into 17 different functional groups. Upregulation of
      eight heat shock, oxidative response and amino acid biosynthesis-related proteins
      (e.g. Hsp78p, Ssa1p, Hsp60p, Ctt1p, Sod1p, Ahp1p, Met6p and Met17p), which may
      jointly maintain the cell redox homeostasis, was dependant on inoculation
      density. Significant increases in the levels of five proteins involved in
      glycolysis and alcohol biosynthesis pathways (e.g. Glk1p, Fba1p, Eno1p, Pdc1p and
      Adh1p) might play critical roles in improving ethanol productivity of the
      fermentation process and shortening the fermentation time when inoculation sizes
      were increased. Cell-density-dependent glycolytic variations of proteins involved
      in trehalose, glycerol biosynthesis and pentose phosphate pathway revealed shifts
      among metabolic pathways during fermentation with different inoculation sizes.
      Upregulation of three signal transduction proteins (Bmh1p, Bmh2p and Fpr1p)
      indicated that adequate cell-cell contacts improved cellular communication at
      high inoculation sizes. These findings provide insights into yeast responses to
      inoculation size and optimizing the direct inoculation of active dry yeast
      fermentation, so as to improve the ethanol production.

PMID- 19743422
TI  - Proteolysis during long-term glucose starvation in Staphylococcus aureus COL.
AB  - A combination of pulse-chase experiments and 2-D PAGE revealed that protein
      degradation appears to play a crucial role for the cell physiology of
      Staphylococcus aureus COL during extended periods of glucose starvation. The
      synthesis rate of virtually all cytosolic and radioactively labeled proteins from
      growing cells seemed dramatically reduced in the first 3.5 h of glucose
      starvation. The stability of proteins synthesized in growing cells was monitored
      by a pulse-chase approach on a proteome wide scale. Especially, enzymes involved
      in nucleic acid and amino acid biosyntheses, energy metabolism and biosynthesis
      of cofactors were found rather rapidly degraded within the onset of the
      stationary phase, whereas the majority of glycolytic and tricarboxylic acid cycle
      enzymes remained more stable. Furthermore, single enzymes of biosynthetic
      pathways were differentially degraded. A metabolite analysis revealed that
      glucose completely depleted from the medium in the transient phase, and amino
      acids such as alanine and glycine were taken up by the cells in the stationary
      phase. We suggest that vegetative proteins no longer required in non-growing
      cells and thus no longer protected by integration into functional complexes were
      degraded. Proteolysis of putative non-substrate-bound or "unemployed" proteins
      appears to be a characteristic feature of S. aureus in order to access nutrients
      as an important survival strategy under starvation conditions.

PMID- 19743423
TI  - Interaction networks: lessons from large-scale studies in yeast.
AB  - Saccharomyces cerevisiae is the simplest eukaryotic model organism and has made
      countless contributions to cell biology. The ease with which it can be
      genetically manipulated has made it a favourite organism among technologists for
      developing methods for large-scale analysis based on reverse genetics.
      Consequently, more genomewide datasets describing aspects of gene and protein
      biology are available for yeast than for any other organism. This has led to the
      pioneering of many computational analysis techniques using yeast data. Here, we
      make a brief survey of yeast physical and genetic interaction networks,
      highlighting major experimental and computational achievements first described in
      this organism.

PMID- 19743424
TI  - Recent advances in yeast organelle and membrane proteomics.
AB  - Yeast proteome research comprises two different aspects: with respect to systemic
      fungal infections (fungemias), invasive candidiasis, for instance by Candida
      albicans, is among the most common causes of morbidity and mortality particularly
      in the expanding population of immunocompromised patients, which rises a high
      medical and pharmaceutical interest in this facultative pathogenic organism.
      Apart from its clinical relevance, yeast research moreover provides an
      indispensable source of knowledge regarding fundamental biochemical processes of
      eukaryotic cells. In this context, the budding yeast Saccharomyces cerevisiae is,
      in addition to its multiple industrial applications, one of the most extensively
      used microorganisms and serves as the best understood eukaryotic model system so
      far. Consequently, numerous studies have focused on gaining insight into the
      yeast proteome, with protein MS providing a very efficient technology to cope
      with this task since it enables both protein identification and differential
      quantification of cellular material. In this review we present an overview of
      recent advances in yeast organelle and membrane proteomics focusing on the cell
      wall, plasma membrane, mitochondria and vacuole.

PMID- 19743425
TI  - Improving soil protein extraction for metaproteome analysis and glomalin-related
      soil protein detection.
AB  - Soil contains low amounts of protein but high amounts of interfering substances.
      Current extraction methods for soil protein cannot produce high-quality samples
      suitable for proteomic analysis. To resolve the problem, we devised a sequential
      extraction method, through sequentially extracting soil in citrate and SDS
      buffers, followed by phenol extraction. The method allows for obtaining
      applicable 1-D and 2-D protein profiles with various agricultural soils and
      detecting glomalin-related soil protein. The method may be a valuable tool for
      soil proteomics.

PMID- 19743426
TI  - Yeast proteome map (last update).
AB  - The identification of proteins separated on 2-D gels is essential to exploit the
      full potential of 2-D gel electrophoresis for proteomic investigations. For this
      purpose we have undertaken the systematic identification of Saccharomyces
      cerevisiae proteins separated on 2-D gels. We report here the identification by
      mass spectrometry of 100 novel yeast protein spots that have so far not been
      tackled due to their scarcity on our standard 2-D gels. These identifications
      extend the number of protein spots identified on our yeast 2-D proteome map to
      716. They correspond to 485 unique proteins. Among these, 154 were resolved into
      several isoforms. The present data set can now be expanded to report for the
      first time a map of 363 protein isoforms that significantly deepens our knowledge
      of the yeast proteome. The reference map and a list of all identified proteins
      can be accessed on the Yeast Protein Map server (www.ibgc.u-bordeaux2.fr/YPM).

PMID- 19743428
TI  - Quantitative proteomics in biological research.
AB  - Proteomics has enabled the direct investigation of biological material, at first
      through the analysis of individual proteins, then of lysates from cell cultures,
      and finally of extracts from tissues and biopsies from entire organisms. Its
      latest manifestation - quantitative proteomics - allows deeper insight into
      biological systems. This article reviews the different methods used to extract
      quantitative information from mass spectra. It follows the technical developments
      aimed toward global proteomics, the attempt to characterize every expressed
      protein in a cell by at least one peptide. When applications of the technology
      are discussed, the focus is placed on yeast biology. In particular, differential
      quantitative proteomics, the comparison between an experiment and its control, is
      very discriminating for proteins involved in the process being studied. When
      trying to understand biological processes on a molecular level, differential
      quantitative proteomics tends to give a clearer picture than global transcription
      analyses. As a result, MS has become an even more indispensable tool for
      biochemically motivated biological research.

PMID- 19743427
TI  - Engineering of the fluorescent-energy-conversion arm of phi29 DNA packaging motor
      for single-molecule studies.
AB  - The bacteriophage phi29 DNA packaging motor contains a protein core with a
      central channel comprising twelve copies of re-engineered gp10 protein geared by
      six copies of packaging RNA (pRNA) and a DNA packaging protein gp16 with unknown
      copies. Incorporation of this nanomotor into a nanodevice would be beneficial for
      many applications. To this end, extension and modification of the motor
      components are necessary for the linkage of this motor to other nanomachines.
      Here the re-engineering of the motor DNA packaging protein gp16 by extending its
      length and doubling its size using a fusion protein technique is reported. The
      modified motor integrated with the eGFP-gp16 maintains the ability to convert the
      chemical energy from adenosine triphosphate (ATP) hydrolysis to mechanical motion
      and package DNA. The resulting DNA-filled capsid is subsequently converted into
      an infectious virion. The extended part of the gp16 arm is a fluorescent protein
      eGFP, which serves as a marker for tracking the motor in single-molecule studies.
      The activity of the re-engineered motor with eGFP-gp16 is also observed directly
      with a bright-field microscope via its ability to transport a 2-microm-sized
      cargo bound to the DNA.

PMID- 19743429
TI  - When less can yield more - Computational preprocessing of MS/MS spectra for
      peptide identification.
AB  - The effectiveness of database search algorithms, such as Mascot, Sequest and
      ProteinPilot is limited by the quality of the input spectra: spurious peaks in
      MS/MS spectra can jeopardize the correct identification of peptides or reduce
      their score significantly. Consequently, an efficient preprocessing of MS/MS
      spectra can increase the sensitivity of peptide identification at reduced file
      sizes and run time without compromising its specificity. We investigate the
      performance of 25 MS/MS preprocessing methods on various data sets and make
      software for improved preprocessing of mgf/dta-files freely available from
      http://hci.iwr.uni-heidelberg.de/mip/proteomics or
      http://www.childrenshospital.org/research/steenlab.

PMID- 19743430
TI  - Modification-specific proteomics: strategies for characterization of post
      translational modifications using enrichment techniques.
AB  - More than 300 different types of protein post-translational modifications (PTMs)
      have been described, many of which are known to have pivotal roles in cellular
      physiology and disease. Nevertheless, only a handful of PTMs have been
      extensively investigated at the proteome level. Knowledge of protein substrates
      and their PTM sites is key to dissection of PTM-mediated cellular processes. The
      past several years have seen a tremendous progress in developing MS-based
      proteomics technologies for global PTM analysis, including numerous studies of
      yeast and other microbes. Modification-specific enrichment techniques combined
      with advanced MS/MS methods and computational data analysis have revealed a
      surprisingly large extent of PTMs in proteins, including multi-site, cooperative
      modifications in individual proteins. We review some of the current strategies
      employed for enrichment and detection of PTMs in modification-specific
      proteomics.

PMID- 19743431
TI  - Silica-templated synthesis of ordered mesoporous tungsten carbide/graphitic
      carbon composites with nanocrystalline walls and high surface areas via a
      temperature-programmed carburization route.
AB  - Ordered mesostructured tungsten carbide and graphitic carbon composites (WC/C)
      with nanocrystalline walls are fabricated for the first time by a temperature
      programmed carburization approach with phosphotungstic acid (PTA) as a precursor
      and mesoporous silica materials as hard templates. The mesostructure, crystal
      phase, and amount of deposited graphitic carbon can be conveniently tuned by
      controlling the silica template (SBA-15 or KIT-6), carburizing temperature (700
      1000 degrees C), the PTA-loading amount, and the carburizing atmosphere (CH(4) or
      a CH(4)/H(2) mixture). A high level of deposited carbon is favorable for
      connecting and stabilizing the WC nanocrystallites to achieve high mesostructural
      regularity, as well as promoting the carburization reaction. Meanwhile, large
      pore sizes and high mesoporosity of the silica templates can promote WC-phase
      formation. These novel, ordered, mesoporous WC/C nanocomposites with high surface
      areas (74-169 m(2) g(-1)), large pore volumes (0.14-0.17 cm(3) g(-1)), narrow
      pore-size distributions (centered at about 3 nm), and very good oxidation
      resistance (up to 750 degrees C) have potential applications in fuel-cell
      catalysts and nanodevices.

PMID- 19743432
TI  - Growth of single-walled carbon nanotubes from sharp metal tips.
AB  - The nucleation and growth of single-walled carbon nanotubes is observed in situ
      in a transmission electron microscope. Carbon atoms are implanted into
      catalytically active metal particles by electron-beam sputtering. The metal
      particles are then shaped with a focused electron beam. Once the particles have a
      region of high surface curvature, spontaneous nucleation and growth of single
      walled carbon nanotubes occurs on the metal particles. It is shown that the local
      solubility of carbon in the metal determines the nucleation of nanotubes. This is
      confirmed by atomistic computer simulations treating the solubility of carbon in
      a metal particle as a function of the size of the system.

PMID- 19743433
TI  - In vivo quantum-dot toxicity assessment.
AB  - Quantum dots have potential in biomedical applications, but concerns persist
      about their safety. Most toxicology data is derived from in vitro studies and may
      not reflect in vivo responses. Here, an initial systematic animal toxicity study
      of CdSe-ZnS core-shell quantum dots in healthy Sprague-Dawley rats is presented.
      Biodistribution, animal survival, animal mass, hematology, clinical biochemistry,
      and organ histology are characterized at different concentrations (2.5-15.0 nmol)
      over short-term (<7 days) and long-term (>80 days) periods. The results show that
      the quantum dot formulations do not cause appreciable toxicity even after their
      breakdown in vivo over time. To generalize the toxicity of quantum dots in vivo,
      further investigations are still required. Some of these investigations include
      the evaluation of quantum dot composition (e.g., PbS versus CdS), surface
      chemistry (e.g., functionalization with amines versus carboxylic acids), size
      (e.g., 2 versus 6 nm), and shape (e.g., spheres versus rods), as well as the
      effect of contaminants and their byproducts on biodistribution behavior and
      toxicity. Combining the results from all of these studies will eventually lead to
      a conclusion regarding the issue of quantum dot toxicity.

PMID- 19743434
TI  - Receptor-mediated cellular uptake of folate-conjugated fluorescent nanodiamonds:
      a combined ensemble and single-particle study.
AB  - Fluorescent nanodiamonds (FNDs) are nontoxic and photostable nanomaterials, ideal
      for long-term in vivo imaging applications. This paper reports that FNDs with a
      size of approximately 140 nm can be covalently conjugated with folic acid (FA)
      for receptor-mediated targeting of cancer cells at the single-particle level. The
      conjugation is made by using biocompatible polymers, such as polyethylene glycol,
      as crosslinked buffer layers. Ensemble-averaged measurements with flow cytometry
      indicate that more than 50% of the FA-conjugated FND particles can be
      internalized by the cells (such as HeLa cells) through receptor-mediated
      endocytosis, as confirmed by competitive inhibition assays. Confocal fluorescence
      microscopy reveals that these FND particles accumulate in the perinuclear region.
      The absolute number of FNDs internalized by HeLa cells after 3 h of incubation at
      a particle concentration of 10 microg mL(-1) is in the range of 100 particles per
      cell. The receptor-mediated uptake process is further elucidated by single
      particle tracking of 35-nm FNDs in three dimensions and real time during the
      endocytosis.

PMID- 19743435
TI  - Magnetic resonance spectroscopy of the occipital cortex and the cerebellar vermis
      distinguishes individual cats affected with alpha-mannosidosis from normal cats.
AB  - A genetic deficiency of lysosomal alpha-mannosidase causes the lysosomal storage
      disease alpha-mannosidosis (AMD), in which oligosaccharide accumulation occurs in
      neurons and glia. The purpose of this study was to evaluate the role of magnetic
      resonance spectroscopy (MRS) in detecting the oligosaccharide accumulation in
      AMD. Five cats with AMD and eight age-matched normal cats underwent in vivo MRS
      studies with a single voxel short echo time (20 ms) STEAM spectroscopy sequence
      on a 4.7T magnet. Two voxels were studied in each cat, from the cerebellar vermis
      and the occipital cortex. Metabolites of brain samples from these regions were
      extracted with perchloric acid and analyzed by high resolution NMR spectroscopy.
      A significantly elevated unresolved resonance signal between 3.4 and 4. ppm was
      observed in the cerebellar vermis and occipital cortex of all AMD cats, which was
      absent in normal cats. This resonance was shown to be from carbohydrate moieties
      by high resolution NMR of tissue extracts. Resonances from the Glc-NAc group (1.8
      2.2 ppm) along with anomeric proton signals (4.6-5.4 ppm) from undigested
      oligosaccharides were also observed in the extract spectra from AMD cats. This
      MRS spectral pattern may be a useful biomarker for AMD diagnosis as well as for
      assessing responses to therapy.

PMID- 19743436
TI  - Laser therapy of twin-to-twin transfusion syndrome in triplet pregnancies.
AB  - OBJECTIVE: Laser coagulation of placental anastomoses in twin pregnancies
      complicated by severe twin-to-twin transfusion syndrome (TTTS) has been shown to
      be superior to serial amniodrainage, and has emerged as the standard therapy for
      this condition. We report the outcome of triplet pregnancies treated with laser
      therapy for severe TTTS. METHODS: From a database containing information on all
      multiple pregnancies referred to our center we identified 20 triplet pregnancies
      with severe TTTS. Sixteen of them were dichorionic, four monochorionic and all
      cases were triamniotic. Perinatal outcome was obtained in all cases. RESULTS:
      Fetoscopy was performed in 18 out of 20 cases at a median gestational age of 19.7
      (range, 17.0-23.3) weeks. Delivery occurred at a median of 31.9 (range, 24.7
      36.4) weeks with an overall fetal survival rate of 65%, at least one surviving
      fetus in 83% of cases and all three fetuses surviving in 39%. CONCLUSION: Laser
      coagulation is an effective treatment for severe TTTS in triplets. However,
      survival rates are lower than in twin pregnancies.

PMID- 19743439
TI  - Towards in vivo flow cytometry.

PMID- 19743442
TI  - Placental insulin-like growth factor II (IGF-II) and its relation to litter size
      in the common marmoset monkey (Callithrix jacchus).
AB  - The primate placenta produces a wide variety of hormones throughout gestation
      that regulate placental function and fetal growth. One such hormone is insulin
      like growth factor-II (IGF-II), a peptide implicated in cell division,
      differentiation, and amino acid transport. IGF-II concentrations were measured in
      23 common marmoset (Callithrix jacchus) term placentas from twin and triplet
      litters in order to determine whether previously described differences in
      fetoplacental phenotype such as placental and litter mass and placental surface
      area were related to differences in endocrine function. IGF-II was extracted from
      frozen tissue samples and measured using an enzyme-linked immunosorbent assay kit
      designed for human tissue, which was validated for marmoset placenta. IGF-II
      concentrations were not related to placental or litter mass, and twin and triplet
      placentas did not differ in total concentration. However, per individual fetus,
      triplets were associated with a significant 42% reduction in IGF-II concentration
      (P = 0.03), and IGF-II concentration per gram of fetal mass was a third lower in
      triplet litters. The triplet placenta exhibits a global expansion of the surface
      area which was contrasted by a per unit area reduction in IGF-II concentration (r
      = -0.75, P = 0.01), a pattern that explains why twin and triplet placentas
      overall did not differ in concentration. Per fetus, triplet pregnancies are
      associated with relatively less maternal mass, placental mass and microscopic
      surface area suggesting that the intrauterine growth of triplets is supported by
      systems that increase the efficiency of nutrient transfer. The finding that
      individual triplet fetuses are also associated with significantly lower IGF-II
      concentrations is consistent with the view that the marmoset fetoplacental unit
      exhibits a flexible pattern of placental allocation and metabolism. Plasticity in
      placental endocrine and metabolic function is likely to play an important role in
      the ability of the fetus to sense and accommodate the intrauterine environment
      and, by extension, the external ecology.

PMID- 19743443
TI  - In vivo fiber-based multicolor photoacoustic detection and photothermal purging
      of metastasis in sentinel lymph nodes targeted by nanoparticles.
AB  - This report introduces a novel diagnostic and therapeutic platform for in vivo
      non-invasive detection and treatment of metastases in sentinel lymph nodes (SLNs)
      at single cell level using an integrated system of multicolor photoacoustic (PA)
      lymph flow cytometry, PA lymphography, absorption image cytometry, and
      photothermal (PT) therapy. A melanoma-bearing mouse model was used to demonstrate
      the capability of this platform for real-time lymphatic mapping, counting of
      disseminated tumor cells (DTCs) in prenodal lymphatics, and detecting metastasis
      in SLNs and its purging. The detection and ablation of non-pigmented breast
      cancer cells in SLNs was achieved by labeling them with nanoparticles. The
      association between DTC count and SLN metastasis progression supports lymphatic
      DTCs as a novel prognostic marker of metastasis. The fiber-based portable PA
      device may replace the conventional SLN(s) excision and histology-based staging.
      The earliest detection of DTCs in the lymphatic vessels before the establishment
      of nodal metastasis may prevent metastasis by well-timed ablation of DTCs.

PMID- 19743444
TI  - Doppler OCT imaging of cytoplasm shuttle flow in Physarum polycephalum.
AB  - The Doppler optical coherence tomography technique was applied to image the
      oscillatory dynamics of protoplasm in the strands of the plasmodium of slime
      mould Physarum polycephalum. Radial contractions of the gel-like walls of the
      strands and the velocity distributions in the sol-like endoplasm streaming along
      the plasmodial strands are imaged. The motility inhibitor effect of carbon
      dioxide on the cytoplasm shuttle flow and strand-wall contraction is shown. The
      optical attenuation coefficient of cytoplasm is estimated.

PMID- 19743445
TI  - Expression of Pou3f3/Brn-1 and its genomic methylation in developing auditory
      epithelium.
AB  - In the mammalian cochlea, both the sensory cells-called hair cells (HCs)-and
      nonsensory cells such as supporting cells (SCs) and mesenchymal cells participate
      in proper auditory function through the expression of various functional
      molecules. During development, expression of certain genes is repressed through
      genomic methylation, one of the major epigenetic regulatory mechanisms. We
      explored the genomic regions that were differentially methylated in rat auditory
      epithelium at postnatal day 1 (P1) and P14 using amplification of intermethylated
      sites (AIMS). An AIMS fragment was mapped to the 3'-flanking region of Pou3f3/Brn
      1. Bisulfite-converted PCR and quantitative methylation-specific PCR showed that
      the methylation frequency of the AIMS region and the adjacent CpG island was
      increased at P14, when the expression of Pou3f3 and the noncoding RNAs nearby
      decreased. Expression of de novo DNA methyltransferases 3a and 3b also suggests a
      role of epigenetic regulation during postnatal inner ear development.
      Immunohistochemical analysis showed that Pou3f3 was expressed specifically in the
      SCs and mesenchymal cells in the cochlea and established that Pou3f3 is a new
      cell-type marker for studying inner ear development. Mice deficient in Pou3f3 or
      Pou3f2 plus Pou3f3 did not exhibit any abnormality in the embryonic cochlea.
      Absence of Pou3f3 affected neither the proliferation nor the differentiation
      activities of HC progenitor cells. Pou3f3 may, however, be important for the
      maintenance or functional development of the postnatal cochlea. This is the first
      report to study involvement of an epigenetic regulatory mechanism in the
      developing mammalian auditory epithelium.

PMID- 19743446
TI  - Digit-specific aberrations in the primary somatosensory cortex in Writer's cramp.
AB  - OBJECTIVE: One approach to the treatment of focal hand dystonia (FHD) is via
      sensory-based training regimes. It is known that FHD patients demonstrate a
      reduced distance between the representations of digits 1 and 5 and also digits 2
      and 5 in primary somatosensory cortex. However, we lack information on the
      spatial relationships among digits, such as reduced inter-digit spacing or shifts
      of representations within the cortical areas, and whether aberrations are
      specific to symptomatic digits. Our aim was to characterize the spatial
      relationships among individual digits to determine the types of aberrations that
      exist and whether these are specific to symptomatic digits only. METHODS: Using
      high-resolution fMRI over a limited volume and surface-based mapping techniques,
      the cortical representations of all digits of the dystonia-affected hand within
      the sub-regions of the postcentral gyrus were mapped in patients with task
      specific Writer's cramp (WC). RESULTS: In area 3b, digits directly involved in
      writing (D1, D2 and D3) show reduced inter-digit separation, reversals, and
      overlapping activation. The thumb representation occupies territory normally
      occupied by digit 2 in controls. Asymptomatic digits 4 and 5 preserve their inter
      digit separation yet shift towards the D1/D2/D3 cluster, suggesting that reduced
      spacing, not simply digit shifts, are associated with dystonia symptoms. Area 3a
      was less responsive to sensory input in WC patients providing evidence of reduced
      afferent drive or top-down modulation to this sub-region. INTERPRETATION:
      Therapeutic regimes aimed at facilitating inter-digit separation of digits 1, 2
      and 3 may promote beneficial plasticity in WC patients.

PMID- 19743447
TI  - Treatment of multiple myeloma in patients with Gaucher disease.

PMID- 19743448
TI  - Pivotal studies of orphan drugs approved for neurological diseases.
AB  - OBJECTIVE: To identify design elements of clinical trials leading to US Food and
      Drug Administration approval of drugs for neurological diseases with and without
      orphan indications. METHODS: We used publicly available information to identify
      approvals for drugs for neurological diseases with an orphan indication (n = 19)
      and compared them with recent approvals for drugs for neurological diseases
      without an orphan indication (n = 20). We identified "pivotal trials" from drug
      labels and drug approval packages, and assessed them on four elements of clinical
      trial design: control, blinding, randomization, and size. RESULTS: All drugs for
      neurological diseases (100%) approved without an orphan indication included at
      least two randomized, double-blind, placebo-controlled trials. In comparison, 32%
      of drugs with an orphan indication had at least two such trials (p < 0.001) and
      74% had at least one (p = 0.02). Thirty-three pivotal trials were conducted for
      the 19 drugs approved with an orphan indication. Of the 33 trials, 11 (33%) did
      not use a placebo control, 9 (27%) were not double blind, and 4 (12%) were not
      randomized. Drugs approved without an orphan indication had more pivotal trials
      per drug (3.8 vs 1.7 trials; p < 0.001) and a larger mean trial size (506 vs 164
      trial participants; p < 0.001). INTERPRETATION: The US Food and Drug
      Administration has approved orphan drugs for neurological diseases without
      randomized, doubled-blind, placebo-controlled pivotal trials. As orphan drug
      development grows, demand will likely increase for alternative designs for
      conducting adequate and well-controlled studies to demonstrate drug efficacy.

PMID- 19743449
TI  - A neural network critical for spelling.
AB  - We aimed to identify neuroanatomical regions associated with deficits to the
      graphemic buffer, a working memory component of the spelling system that holds
      the sequence of letter identities during production. We evaluated 331 patients
      with left hemisphere ischemic stroke with various spelling tests and magnetic
      resonance diffusion-weighted imaging and perfusion-weighted imaging, within 48
      hours of stroke onset. A voxel-wise statistical map showed that ischemia in
      voxels in posterior and inferior frontal and parietal cortex, subcortical white
      matter underlying prefrontal cortex, lateral occipital gyrus, or caudate was
      associated with impairment in maintaining the sequence of letter identities while
      spelling.

PMID- 19743450
TI  - The neuropathology of probable Alzheimer disease and mild cognitive impairment.
AB  - OBJECTIVE: Mixed pathologies are common in older persons with dementia. Little is
      known about mixed pathologies in probable Alzheimer disease (AD) and about the
      spectrum of neuropathology in mild cognitive impairment (MCI). The objective of
      this study was to investigate single and mixed common age-related
      neuropathologies in persons with probable AD and MCI. METHODS: The study included
      483 autopsied participants from the Religious Orders Study and the Rush Memory
      and Aging Project with probable AD (National Institute of Neurological and
      Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders
      Association criteria), MCI (amnestic and nonamnestic), or no cognitive
      impairment. We excluded 41 persons with clinically possible AD and 14 with other
      dementias. We documented the neuropathology of AD (National Institute on Aging
      Reagan criteria), macroscopic cerebral infarcts, and neocortical Lewy body (LB)
      disease. RESULTS: Of 179 persons (average age, 86.9 years) with probable AD,
      87.7% had pathologically confirmed AD, and 45.8% had mixed pathologies, most
      commonly AD with macroscopic infarcts (n = 54), followed by AD with neocortical
      LB disease (n = 19) and both (n = 8). Of the 134 persons with MCI, 54.4% had
      pathologically diagnosed AD (58.7% amnestic; 49.2% nonamnestic); 19.4% had mixed
      pathologies (22.7% amnestic; 15.3% nonamnestic). Macroscopic infarcts without
      pathologically diagnosed AD accounted for 4.5% of probable AD, 13.3% of amnestic
      MCI, and 18.6% of nonamnestic MCI. Pure neocortical LB disease was uncommon in
      all persons with cognitive impairment (<6%). Microscopic infarcts (without
      macroscopic infarcts) were common as a mixed pathology, but rarely accounted for
      a clinical diagnosis of probable AD (n = 4) or MCI (n = 3). INTERPRETATION:
      Clinically diagnosed probable AD and MCI, even amnestic MCI, are pathologically
      heterogeneous disorders, with many persons exhibiting mixed pathologies.

PMID- 19743453
TI  - Cerebrospinal fluid amyloid beta(40) is decreased in cerebral amyloid angiopathy.
AB  - Cerebral amyloid angiopathy is caused by deposition of the amyloid beta protein
      in the cerebral vasculature. In analogy to previous observations in Alzheimer
      disease, we hypothesized that analysis of amyloid beta(40) and beta(42) proteins
      in the cerebrospinal fluid might serve as a molecular biomarker. We observed
      strongly decreased cerebrospinal fluid amyloid beta(40) (p < 0.01 vs controls or
      Alzheimer disease) and amyloid beta(42) concentrations (p < 0.001 vs controls and
      p < 0.05 vs Alzheimer disease) in cerebral amyloid angiopathy patients. The
      combination of amyloid beta(42) and total tau discriminated cerebral amyloid
      angiopathy from controls, with an area under the receiver operator curve of 0.98.
      Our data are consistent with neuropathological evidence that amyloid beta(40) as
      well as amyloid beta(42) protein are selectively trapped in the cerebral
      vasculature from interstitial fluid drainage pathways that otherwise transport
      amyloid beta proteins toward the cerebrospinal fluid.

PMID- 19743454
TI  - Extensive astrocyte infection is prominent in human immunodeficiency virus
      associated dementia.
AB  - Astrocyte infection with human immunodeficiency virus (HIV) is considered rare,
      so astrocytes are thought to play a secondary role in HIV neuropathogenesis. By
      combining double immunohistochemistry, laser capture microdissection, and highly
      sensitive multiplexed polymerase chain reaction to detect HIV DNA in single
      astrocytes in vivo, we showed that astrocyte infection is extensive in subjects
      with HIV-associated dementia, occurring in up to 19% of GFAP+ cells. In addition,
      astrocyte infection frequency correlated with the severity of neuropathological
      changes and proximity to perivascular macrophages. Our data indicate that
      astrocytes can be extensively infected with HIV, and suggest an important role
      for HIV-infected astrocytes in HIV neuropathogenesis.

PMID- 19743455
TI  - Effect of chorioamnionitis on brain development and injury in premature newborns.
AB  - OBJECTIVE: The association of chorioamnionitis and noncystic white matter injury,
      a common brain injury in premature newborns, remains controversial. Our
      objectives were to determine the association of chorioamnionitis and postnatal
      risk factors with white matter injury, and the effects of chorioamnionitis on
      early brain development, using advanced magnetic resonance imaging. METHODS:
      Ninety-two preterm newborns (24-32 weeks gestation) were studied at a median age
      of 31.9 weeks and again at 40.3 weeks gestation. Histopathological
      chorioamnionitis and white matter injury were scored using validated systems.
      Measures of brain metabolism (N-acetylaspartate/choline and lactate/choline) on
      magnetic resonance spectroscopy, and microstructure (average diffusivity and
      fractional anisotropy) on diffusion tensor imaging were calculated from
      predefined brain regions. RESULTS: Thirty-one (34%) newborns were exposed to
      histopathological chorioamnionitis, and 26 (28%) had white matter injury.
      Histopathological chorioamnionitis was not associated with an increased risk of
      white matter injury (relative risk: 1.2; p = 0.6). Newborns with postnatal
      infections and hypotension requiring therapy were at higher risk of white matter
      injury (p < 0.03). Adjusting for gestational age at scan and regions of interest,
      histopathological chorioamnionitis did not significantly affect brain metabolic
      and microstructural development (p > 0.1). In contrast, white matter injury was
      associated with lower N-acetylaspartate/choline (-8.9%; p = 0.009) and lower
      white matter fractional anisotropy (-11.9%; p = 0.01). INTERPRETATION:
      Histopathological chorioamnionitis does not appear to be associated with an
      increased risk of white matter injury on magnetic resonance imaging or with
      abnormalities of brain development. In contrast, postnatal infections and
      hypotension are associated with an increased risk of white matter injury in the
      premature newborn.

PMID- 19743456
TI  - Fast food and neighborhood stroke risk.
AB  - OBJECTIVE: To investigate the association between the number of fast food
      restaurants and ischemic stroke in neighborhoods. METHODS: This work was a
      prespecified part of the Brain Attack in Corpus Christi (BASIC) project. Ischemic
      stroke cases were prospectively ascertained in Nueces County, Texas. Home
      addresses were geocoded and used to establish the census tract for each stroke
      case. Census tracts were used as proxies for neighborhoods (n = 64). Using a
      standard definition, fast food restaurants were identified from a commercial
      list. Poisson regression was used to study the association between the number of
      fast food restaurants in the neighborhood, using a 1-mile buffer around each
      census tract, and the risk of stroke in the neighborhood. Models were adjusted
      for demographics and neighborhood socioeconomic status (SES). RESULTS: There were
      1,247 completed ischemic strokes from January 2000 through June 2003 and 262 fast
      food restaurants. The median number of fast food restaurants per census tract
      including buffer was 22 (interquartile range, 12-33). Adjusting for neighborhood
      demographics and SES, the association of fast food restaurants with stroke was
      significant (p = 0.02). The association suggested that the risk of stroke in a
      neighborhood increased by 1% for every fast food restaurant (relative risk, 1.01;
      95% confidence interval [CI], 1.00-1.01). The relative risk of stroke comparing
      neighborhoods in the 75th to the 25th percentile of the distribution of fast food
      restaurants was 1.13 (95% CI, 1.02-1.25). INTERPRETATION: Controlling for
      demographic and SES factors, there was a significant association between fast
      food restaurants and stroke risk in neighborhoods in this community-based study.

PMID- 19743458
TI  - Pathogenic CD8(+) T cells in multiple sclerosis.
AB  - Traditionally, autoimmune pathogeneses have been attributed to CD4(+) T
      lymphocytes, as in multiple sclerosis (MS), rheumatoid arthritis, type 1 diabetes
      mellitus, and/or to B lymphocytes, as in myasthenia gravis and systemic lupus
      erythematosus. That is because their primary genetic associations are mostly with
      certain human leukocyte antigen class II alleles, whose gene products present
      antigens to CD4(+) T cells. Because few autoimmune diseases show stronger
      associations with major histocompatibility complex class I alleles (ankylosing
      spondylitis, Behcet's disease, and psoriasis), CD8(+) T cells, which interact
      with major histocompatibility complex class I molecules, have been largely
      ignored in autoimmunity research. However, a variety of findings has recently
      revived interest in this population, particularly in MS. First, it shows
      associations with major histocompatibility complex class I alleles. Second, its
      lesions show a predominance of CD8(+) T cells. Third, these represent effectors
      that can directly damage central nervous system target cells. Furthermore,
      several clinical trials of monoclonal antibodies specifically against CD4(+) T
      cells, or the polarizing cytokines on which they depend, have failed to show any
      therapeutic benefit in MS, unlike broader-spectrum antibodies that deplete all T
      cells. Here, we review the evidence that CD8(+) T cells play a role in MS
      pathogenesis.

PMID- 19743459
TI  - Eating yourself to a stroke?

PMID- 19743460
TI  - Effect of chorioamnionitis on brain development and injury in premature newborns.

PMID- 19743457
TI  - Phase II trial of CoQ10 for ALS finds insufficient evidence to justify phase III.
AB  - OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a devastating, and currently
      incurable, neuromuscular disease in which oxidative stress and mitochondrial
      impairment are contributing to neuronal loss. Coenzyme Q10 (CoQ10), an
      antioxidant and mitochondrial cofactor, has shown promise in ALS transgenic mice,
      and in clinical trials for neurodegenerative diseases other than ALS. Our aims
      were to choose between two high doses of CoQ10 for ALS, and to determine if it
      merits testing in a Phase III clinical trial. METHODS: We designed and
      implemented a multicenter trial with an adaptive, two-stage, bias-adjusted,
      randomized, placebo-controlled, double-blind, Phase II design (n = 185). The
      primary outcome in both stages was a decline in the ALS Functional Rating Scale
      revised (ALSFRSr) score over 9 months. Stage 1 (dose selection, 35 participants
      per group) compared CoQ10 doses of 1,800 and 2,700 mg/day. Stage 2 (futility
      test, 75 patients per group) compared the dose selected in Stage 1 against
      placebo. RESULTS: Stage 1 selected the 2,700 mg dose. In Stage 2, the pre
      specified primary null hypothesis that this dose is superior to placebo was not
      rejected. It was rejected, however, in an accompanying prespecified sensitivity
      test, and further supplementary analyses. Prespecified secondary analyses showed
      no significant differences between CoQ10 at 2,700 mg/day and placebo. There were
      no safety concerns. INTERPRETATION: CoQ10 at 2,700 mg daily for 9 months shows
      insufficient promise to warrant Phase III testing. Given this outcome, the
      adaptive Phase II design incorporating a dose selection and a futility test
      avoided the need for a much larger conventional Phase III trial.

PMID- 19743461
TI  - Dystonia: a sensory and motor disorder of short latency inhibition.

PMID- 19743462
TI  - Treatment disparities in Parkinson's disease.
AB  - We sought to identify racial disparities in the treatment of Parkinson's disease
      (PD). We identified 307 incident PD cases using Pennsylvania State Medicaid
      claims, and extracted claims for medications, physical therapy, and healthcare
      visits for the 6 months after diagnosis. After controlling for age, sex, and
      geography, African-Americans were four times less likely than whites to receive
      any PD treatment (odds ratio, 0.24; 95% confidence interval, 0.09-0.64),
      especially indicated medications. In a group with the same healthcare insurance,
      disparities in PD treatment exist. Physician and community awareness of these
      racial differences in PD treatment is the first step in addressing healthcare
      disparities.

PMID- 19743464
TI  - Disparities in care: guilty until proven innocent.

PMID- 19743465
TI  - The course and correlates of high hospital utilization in sickle cell disease:
      Evidence from a large, urban Medicaid managed care organization.
AB  - Although most patients with sickle cell disease (SCD) are hospitalized
      infrequently and manage painful crises at home, a small subpopulation is
      frequently admitted to emergency departments and inpatient units. This small
      group accounts for the majority of health care expenses for patients with SCD.
      Using inpatient claims data from a large, urban Medicaid MCO for 5 consecutive
      years, this study sought to describe the course of high inpatient utilization
      (averaging four or more admissions enrolled per year for at least 1 year) in
      members with a diagnosis of SCD and a history of hospitalizations for vaso
      occlusive crisis. High utilizers were compared with the other members with SCD on
      demographics, medical and psychiatric comorbidity, and use of other health care
      resources. Members who were high utilizers had more diagnostic mentions of sickle
      cell complications than low utilizers. However, the pattern of high inpatient
      utilization was likely to moderate over successive years, and return to the
      pattern after moderation was uncommon. Despite this, a small subpopulation
      engaged in exceptional levels of inpatient utilization over multiple years.

PMID- 19743466
TI  - Randomized sequential trial of valproic acid in amyotrophic lateral sclerosis.
AB  - OBJECTIVE: To determine whether valproic acid (VPA), a histone deacetylase
      inhibitor that showed antioxidative and antiapoptotic properties and reduced
      glutamate toxicity in preclinical studies, is safe and effective in amyotrophic
      lateral sclerosis (ALS) using a sequential trial design. METHODS: Between April
      2005 and January 2007, 163 ALS patients received VPA 1,500mg or placebo daily.
      Primary end point was survival. Secondary outcome measure was decline of
      functional status measured by the revised ALS Functional Rating Scale. Analysis
      was by intention to treat and according to a sequential trial design. This trial
      was registered with ClinicalTrials.gov (number NCT00136110). RESULTS: VPA did not
      affect survival (cumulative survival probability of 0.72 in the VPA group
      [standard error (SE), 0.06] vs 0.88 in the placebo group [SE, 0.04] at 12 months,
      and 0.59 in the VPA group [SE, 0.07] vs 0.68 in the placebo group [SE, 0.08] at
      16 months) or the rate of decline of functional status. VPA intake did not cause
      serious adverse reactions. INTERPRETATION: Our finding that VPA, at a dose used
      in epilepsy, does not show a beneficial effect on survival or disease progression
      in patients with ALS has implications for future trials with histone deacetylase
      inhibitors in ALS and other neurodegenerative diseases. The use of a sequential
      trial design allowed inclusion of only half the number of patients required for a
      classic trial design and prevented patients from unnecessarily continuing
      potentially harmful study medication.

PMID- 19743467
TI  - Circulating endothelial microparticles as a marker of cerebrovascular disease.
AB  - OBJECTIVE: Circulating endothelial microparticles (EMPs) have been reported to
      reflect vascular damage. Detailed profiling of these blood endothelial markers
      may adumbrate the pathogenesis of stroke or enable determination of the risk for
      stroke. We investigated EMP profiles in patients at risk for cerebrovascular
      disease. METHODS: We prospectively examined 348 consecutive patients: 73 patients
      with acute stroke and 275 patients with vascular risk factors but no stroke
      events. We quantified various types of EMPs by flow cytometry using CD31, CD42b,
      annexin V (AV), and CD62E antibodies in the peripheral blood of patients. This
      method allowed fractionation of CD31(+)/CD42b(-), CD31(+)/AV(+), and CD62E(+)
      EMPs. Clinical and laboratory factors associated with EMPs were assessed.
      RESULTS: Recent ischemic episodes were found to be more strongly associated with
      greater CD62E(+) EMP levels than with levels of other phenotypes. Increased
      National Institutes of Health Stroke Scale scores and infarct volumes in acute
      stroke patients were significantly associated with greater CD62E(+) EMP levels.
      In the risk factor group, patients with extracranial arterial stenosis had
      greater CD62E(+) EMP levels, whereas those with intracranial arterial stenosis
      had greater CD31(+)/CD42b(-) and CD31(+)/AV(+) EMP levels. The ratio of CD62E(+)
      to CD31(+)/CD42b(-) or CD31(+)/AV(+) EMP level significantly discriminated
      extracranial and intracranial arterial stenosis. INTERPRETATION: Circulating EMP
      phenotypic profiles reflect distinct phenotypes of cerebrovascular disease and
      are markers of vascular pathology and an increased risk for ischemic stroke.

PMID- 19743468
TI  - Pulmonary thrombi are not detected by 3D magnetic resonance angiography in adults
      with sickle cell anemia and an elevated triscuspid regurgitant jet velocity.

PMID- 19743469
TI  - Inhibitory actions of the gamma-aminobutyric acid in pediatric Sturge-Weber
      syndrome.
AB  - OBJECTIVE: The mechanisms of epileptogenesis in Sturge-Weber syndrome (SWS) are
      unknown. We explored the properties of neurons from human pediatric SWS cortex in
      vitro and tested in particular whether gamma-aminobutyric acid (GABA) excites
      neurons in SWS cortex, as has been suggested for various types of epilepsies.
      METHODS: Patch-clamp and field potential recordings and dynamic biphoton imaging
      were used to analyze cortical tissue samples obtained from four 6- to 14-month
      old pediatric SWS patients during surgery. RESULTS: Neurons in SWS cortex were
      characterized by a relatively depolarized resting membrane potential, as was
      estimated from cell-attached recordings of N-methyl-D-aspartate channels. Many
      cells spontaneously fired action potentials at a rate proportional to the level
      of neuronal depolarization. The reversal potential for GABA-activated currents,
      assessed by cell-attached single channel recordings, was close to the resting
      membrane potential. All spontaneously firing neurons recorded in cell-attached
      mode or imaged with biphoton microscopy were inhibited by GABA. Spontaneous
      epileptiform activity in the form of recurrent population bursts was suppressed
      by glutamate receptor antagonists, the GABA(A) receptor agonist isoguvacine, and
      the positive allosteric GABA(A) modulator diazepam. Blockade of GABA(A) receptors
      aggravated spontaneous epileptiform activity. The NKCC1 antagonist bumetanide had
      little effect on epileptiform activity. INTERPRETATION: SWS cortical neurons have
      a relatively depolarized resting membrane potential and spontaneously fire action
      potentials that may contribute to increased network excitability. In contrast to
      previous data depicting excitatory and proconvulsive actions of GABA in certain
      pediatric and adult epilepsies, GABA plays mainly an inhibitory and
      anticonvulsive role in SWS pediatric cortex.

PMID- 19743470
TI  - Heat opens axon initial segment sodium channels: a febrile seizure mechanism?
AB  - OBJECTIVE: A number of hypotheses have been put forward as to why humans respond
      to fever by seizing. The current leading hypotheses are that respiratory
      alkalosis produces an as yet unidentified change in neural excitability or that
      inflammatory mediators potentiate excitatory synaptic transmission. However, it
      is well known that ion channel gating rates increase with increased temperature.
      Furthermore, skeletal and cardiac sodium channel activation can be temperature
      sensitive in some situations. We measured the temperature sensitivity of the
      brain sodium channel, Na(V)1.2, to determine whether febrile temperatures might
      produce a direct increase in neuronal excitability. METHODS: The effect of
      temperature on Na(V)1.2 electrophysiological properties was measured in a
      transfected mammalian cell line. The subcellular location of Na(V)1.2 in the
      mouse brain was ascertained using antibodies against Na(V)1.2 and ankyrin-G.
      Computer simulation of a hippocampal granule cell model was used to predict the
      effect of temperature on action potential firing. RESULTS: As well as the
      expected increase in gating rates, the voltage dependence of activation became
      7.6 mV more negative when the temperature was increased from 37 degrees C to 41
      degrees C. Na(V)1.2 was localized to the axon initial segment in hippocampal and
      cortical neurons. Computer simulation showed that increased gating rates and the
      more negative activation dramatically increase neuronal excitability.
      INTERPRETATION: The direct effect of heat on ion channels localized to the site
      of action potential initiation potentially causes a profound increase in neuronal
      excitability. This is likely to contribute to febrile seizure genesis.

PMID- 19743471
TI  - Myosin IIB isoform plays an essential role in the formation of two distinct types
      of macropinosomes.
AB  - The function and mechanism of macropinocytosis in cells outside of the immune
      system remain poorly understood. We used a neuroblastoma cell line, Neuro-2a, to
      study macropinocytosis in neuronal cells. We found that phorbol 12-myristate 13
      acetate (PMA) and insulin-like growth factor 1 (IGF-1) induced two distinct types
      of macropinocytosis in the Neuro-2a cells. IGF-1-induced macropinocytosis occurs
      mostly around the cell bodies and requires phosphoinositide 3-kinase (PI3K),
      while PMA-induced macropinocytosis occurs predominantly in the neurites and is
      independent of PI3K activity. Both types of macropinocytosis were inhibited by a
      specific inhibitor of nonmuscle myosin II, blebbistatin. siRNA knockdown of
      nonmuscle myosin II isoforms, -IIA and -IIB, resulted in opposite effects on
      macropinocytosis induced by PMA or IGF. Myosin IIA knockdown significantly
      increased, whereas myosin IIB knockdown significantly decreased, macropinocytosis
      with correlating changes in membrane ruffle formation.

PMID- 19743472
TI  - Administration of a mutated myostatin propeptide to neonatal mice significantly
      enhances skeletal muscle growth.
AB  - Myostatin is a dominant inhibitor of skeletal muscle development and growth. As
      transgenic over-expression of myostatin propeptide dramatically enhanced muscle
      mass, we hypothesized that administration of myostatin propeptide will increase
      muscle growth. In this study, the wild-type form of porcine myostatin propeptide
      and its mutated form at the cleavage site of metalloproteinases of BMP-1/TLD
      family were produced from insect cells. In vitro A204 cells reporter assays
      showed that both wild-type and the mutated propeptides depressed myostatin
      activity. The recombinant propeptides at four-fold myostatin concentration can
      effectively block myostatin function during co-incubation with A204 cells. In
      particular, the mutated propeptide appeared much more effective than wild-type
      propeptide over a long period during the in vitro co-incubation. Administration
      of the mutated propeptide to neonatal mice at the age of 11 and 18 days was
      tested and showed significant increase in growth performance by 11-15% from the
      age of 25 to 57 days (P < 0.05). The major skeletal muscles of mice that were
      injected with mutated propeptide were 13.5-24.8% heavier than the control group
      (P < 0.05) as a result of muscle fiber hypertrophy. In conclusion, administration
      of the mutated myostatin propeptide during the neonatal period is an effective
      way for promoting muscle growth.

PMID- 19743475
TI  - Impaired active demethylation of the paternal genome in pronuclear-stage rat
      zygotes produced by in vitro fertilization or intracytoplasmic sperm injection.
AB  - This study was designed to investigate the effect of in vitro production systems
      of rat zygotes such as in vitro fertilization (IVF) and intracytoplasmic sperm
      injection (ICSI) on demethylation dynamics of the paternal genome. Immunostaining
      with anti-5-methylcytosine indicated that in vivo derived zygotes harvested at 20
      hr post-hCG injection had no active demethylation of paternal genomes as a mean
      relative methylation (RM) value, total fluorescence in the paternal genome
      divided by that in maternal one, at 1.17. Leaving zygotes in vivo or in culture
      for an additional 4 or 8 hr resulted in significant decreases of RM values to
      0.14-0.31. Since in vitro-derived zygotes were produced using oocytes harvested
      at 14 hr post-hCG injection, zygotes at 6 hr after IVF or ICSI were considered
      developmentally comparable to the in vivo derived zygotes harvested at 20 hr post
      hCG injection, with RM values at 1.04 and 0.92, respectively. At 10 hr post-IVF
      and ICSI, the RM values of the in vitro derived zygotes decreased significantly,
      but to a lesser extent compared with in vivo derived zygotes, to 0.53 and 0.62,
      respectively, without further decreases at 14 hr. Treatment of IVF-derived
      zygotes with 5-aza-2'-deoxycytidine (5-azadC; an inhibitor for methylation) or
      trichostatin A (TSA; an inhibitor for deacetylation) resulted in the decreased RM
      values at 14 hr post-IVF. However, developmental potential of the 5-azadC- or TSA
      treated IVF zygotes up to the blastocyst stage was not improved. Thus, the
      demethylation dynamics of the paternal genome in pronuclear-stage rat zygotes was
      impaired by routine protocols for in vitro embryo production such as IVF and
      ICSI.

PMID- 19743476
TI  - Massive trauma and the healing role of reparative justice.
AB  - In this article, the author focuses on victims/survivors' experiences of justice
      processes after massive trauma. Reparative justice insists that every step
      throughout the justice experience--from the first moment of the court's encounter
      with a potential witness, to the follow-up of witnesses after their return home,
      to the aftermath of the completion of the case--presents an opportunity for
      redress and healing. Conversely, this experience may present a risk of missing
      opportunities for healing and reintegrating victims into their societies, or,
      worse, (re)victimizing and (re)traumatizing them. Although restitution,
      rehabilitation, or compensation may come only after this process has concluded,
      opportunities exist throughout. Although not sufficient in itself, reparative
      justice is a necessary component among the healing processes after massive
      trauma.

PMID- 19743477
TI  - Selected highlights of the ISTSS 2008 Annual Meeting.

PMID- 19743478
TI  - Should PTSD Criterion A be retained?
AB  - Criterion A has been controversial since its inception, partially because it
      performs a key gate keeping function. Major criticisms of Criterion A of the
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV;
      American Psychiatric Association, 1994) include that it has resulted in
      "criterion creep." The authors tested the hypothesis that a nonrestrictive
      definition would substantially increase posttraumatic stress disorder (PTSD)
      prevalence by determining PTSD based on Criteria B, C, D, E, and F, without
      restricting Criterion A in large probability samples of U.S. adolescents and
      Florida adults. Few PTSD cases occurred in the absence of Criterion A1 events,
      providing little support for the criterion creep hypothesis. Specific
      recommendations are to retain Criterion A; permit additional events; consider
      expanding Criterion A2; consider that either Criterion A1 or A2 be met; and place
      greater emphasis on Criterion F.

PMID- 19743479
TI  - Human rights and the trauma model: genuine partners or uneasy allies?
AB  - Since World War II, a comprehensive body of international law has developed to
      protect and promote human rights. Three generations of rights can be delineated:
      civil and political; economic, social and cultural; and collective rights. The
      convergence of a medical rights-based campaign in the late 1970s with the
      emergence of the new trauma model resulted in mental health professionals playing
      a prominent role in documenting and protecting civil and political rights.
      Economic, social, and cultural rights also emerged as being pivotal, particularly
      in the Australian context as mental health professionals began to work with
      excluded populations such as asylum seekers. Consideration of third-generation
      rights raises important questions about the responsibilities facing mental health
      professionals applying the trauma model to non-Western settings.

PMID- 19743480
TI  - Reformulating PTSD for DSM-V: life after Criterion A.
AB  - The diagnosis of posttraumatic stress disorder has been criticized on numerous
      grounds, but principally for three reasons (a) the alleged pathologizing of
      normal events, (b) the inadequacy of Criterion A, and (c) symptom overlap with
      other disorders. The authors review these problems along with arguments why the
      diagnosis is nevertheless worth retaining in an amended form. A proposal for the
      fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM
      V) is put forward that involves abolishing Criterion A, narrowing the B criteria
      to focus on the core phenomena of flashbacks and nightmares, and narrowing the C
      and D criteria to reduce overlap with other disorders. The potential advantages
      and disadvantages of this formulation are discussed.

PMID- 19743481
TI  - Is posttraumatic stress disorder a stress-induced fear circuitry disorder?
AB  - Neuroimaging studies of posttraumatic stress disorder (PTSD) have reported
      functional abnormalities in brain regions involved in fear conditioning,
      extinction, and emotion regulation. These findings have prompted researchers to
      consider whether PTSD can be characterized as a stress-induced fear circuitry
      disorder. In this review, the authors summarize the results of functional
      neuroimaging studies and conclude that there is a strong argument for
      characterizing PTSD as a stress-induced fear circuitry disorder. They also
      acknowledge that (a) fear is not the only emotion associated with PTSD, (b) a
      state of fear is not required to observe fear-circuitry abnormalities in this
      disorder, and (c) not all functional abnormalities in PTSD are related to fear
      circuitry. Implications for future diagnostic classifications are discussed.

PMID- 19743482
TI  - Imaging chiroptical artifacts.
AB  - It is well-known that circular dichroism (CD) measurements of anisotropic media
      may contain artifacts that result from mixed linear anisotropies. Such artifacts
      are generally considered a nuisance. However, systematic artifacts, carefully
      measured, may contain valuable information. Herein, polycrystalline spherulites
      of D-sorbitol grown from the melt were analyzed with a Mueller matrix microscope,
      among other differential polarization images devices. As spherulites grew into
      one another they developed strong apparent optical rotation and CD signals at the
      boundaries between spherulites. These signals are shown not to have a chiroptical
      origin but rather result from the interactions of linear anisotropies in
      polycrystalline bodies. Such chiroptical artifacts should not be dismissed
      reflexively. Rather, they are comprehensible crystal-optical effects that serve
      to define mesoscale structure.

PMID- 19743483
TI  - Bile acids in asymmetric synthesis and chiral discrimination.
AB  - An overview on the use of bile acid-based compounds able to catalyze
      transformations, control the stereochemical course of a given reaction, recognize
      and bind other molecules, is presented. The recent developments in inclusion
      discrimination of chiral and achiral guests and enantioselective recognition
      achieved by bile acid are described with suitable examples.

PMID- 19743484
TI  - Production of (R)-1-phenylethanols through bioreduction of acetophenones by a new
      fungus isolate Trichothecium roseum.
AB  - A total of 120 fungal strains were isolated from soil samples and evaluated in
      the bioreduction of substituted acetophenones to the corresponding (R)-alcohols.
      Among these strains, isolate Trichothecium roseum EBK-18 was highly effective in
      the production of (R)-alcohols with excellent enantioselectivity (ee > 99%). Gram
      scale preparation of (R)-1-phenylethanol is reported.

PMID- 19743485
TI  - High-performance liquid chromatography separation of enantiomers of mandelic acid
      and its analogs on a chiral stationary phase.
AB  - The enantiomers of mandelic acid and its analogs have been chromatographically
      separated on a chiral stationary phase (CSP) derived from 4-(3,5
      dinitrobenzamido) tetrahydrophenanthrene. The rationale of separations of these
      compounds is discussed with respect to the method development for determining
      enantiomeric purity and possibility of obtaining enantiomerically pure materials
      by high-pressure liquid chromatography. The relationship of analyte structure to
      the extent of enantiomeric separation has been examined and separation factors
      (alpha) are presented for various groups of structurally related compounds.
      Chiral recognition models have been suggested to account for the observed
      separations. These models provide mechanistic insights into the chiral
      recognition process.

PMID- 19743486
TI  - Determination of the absolute configuration of the natural product Klaivanolide
      via density functional calculations of vibrational circular dichroism (VCD).
AB  - The absolute configuration (AC) of the antiprotozoal lactone, Klaivanolide, 1,
      from Uvaria klaineana, has been determined using Vibrational Circular Dichroism
      (VCD) spectroscopy. The experimental VCD spectrum of the (+) enantiomer of 1 was
      measured. To analyze the AC of (+)-1, the conformationally-averaged VCD spectrum
      of 7-S-1 was calculated using density functional theory (DFT) and the GAUSSIAN 03
      program. The B3PW91/TZ2P conformationally-averaged VCD spectrum of 7-S-1 proves
      that the AC of 1 is 7-S-(+).

PMID- 19743487
TI  - Gas phase optical rotation calculated from coupled cluster theory with zero-point
      vibrational corrections from density funcional theory.
AB  - Molecular vibrations can have a significant influence on gas phase specific
      optical rotations. Mainly due to the large number of nuclear degrees of freedom
      in most chiral molecules, theoretical predictions of vibrational corrections
      quickly become prohibitively expensive. Here, we investigate an approach in which
      the purely electronic contribution is calculated at the coupled cluster singles
      and doubles level, while the zero-point vibrational correction is computed using
      the less demanding density functional theory (B3LYP functional). By comparing to
      experimental gas phase results for seven molecules and two wavelengths, we find
      that the mixed coupled cluster/B3LYP approach performs significantly better than
      pure B3LYP predictions. In fact, we find that it is more important to use high
      level electron correlation for the electronic contribution than to include zero
      point vibrational corrections.

PMID- 19743488
TI  - Long-term clinical outcomes after angiographically defined very late stent
      thrombosis of drug-eluting stent.
AB  - BACKGROUND: The advent of drug-eluting stent (DES) use has raised concerns
      regarding later occurring stent thrombosis, especially very late stent thrombosis
      (VLST), and little is known about long-term clinical outcomes after VLST
      occurrence. HYPOTHESIS: Long-term clinical outcomes after detection of VLST may
      be poor. METHOD: We evaluated 3572 consecutive patients who received DES
      implantation from May 2004 to July 2007 at 3 hospitals. The primary outcomes were
      a composite of major adverse cardiac events (MACE) including cardiac death,
      myocardial infarction (MI), target-lesion revascularization (TLR), and target
      vessel revascularization (TVR) after VLST occurrence. RESULTS: We identified 19
      patients (0.53%) with angiographically documented stent thrombosis developing
      over 1 year after DES implantation. The mean time to VLST occurrence was 899 days
      (899 +/- 353). Discontinuation of antiplatelet drugs was noted in 4 (21%)
      patients and the average duration of discontinuation was 4 days. Clinical
      presentations of VLST were mainly MI (17 patients, 89%). Balloon angioplasty was
      only performed in 12 patients (63%) and stent implantation in 7 patients (37%).
      Mean follow-up duration from VLST occurrence was 620 days (620+/-256). During
      clinical follow-up after VLST occurrence, no cardiac deaths or MIs were detected.
      Target-vessel revascularization was done in 2 (11%) patients and TLR in 1 patient
      (6%). Major adverse cardiac events occurred in 3 (16%) patients during long-term
      clinical follow-up. CONCLUSIONS: Clinical presentation of VLST after DES
      implantation is associated with serious adverse events, such as MI. Long-term
      follow-up outcomes after VLST occurrence appear unfavorable and more data from
      larger studies are warranted.

PMID- 19743489
TI  - Transcatheter closure of congenital coronary artery fistulae: immediate and long
      term follow-up results.
AB  - BACKGROUND: Transcatheter closure of coronary artery fistulae (CAF) has emerged
      as an alternative to surgery, but there are no long-term outcome results.
      OBJECTIVE: We report immediate and long-term results in 24 patients after
      transcatheter closure of congenital CAF. METHODS: A total of 24 patients aged 5
      to 56 years old with congenital CAF underwent attempted percutaneous
      transcatheter closure using various devices between November 1998 and August
      2008. The immediate closure results and clinical follow-up were reviewed.
      RESULTS: Of the 24 patients, 20 (83.3%) underwent successful transcatheter
      closure using various devices. An angiogram right after device deployment
      revealed complete occlusion in 15 patients (75%) and trivial- to mild- residual
      flow in 5 patients (25%). Four patients (20%) had transient ST-T wave changes
      after the procedure. The left ventricular end-diastolic volume decreased from
      165+/-31.4 mm3 to 128.6+/-24.4 mm3 (P = 0.012) 24 hours after procedure, and the
      cardiothoracic ratio from 0.57+/-0.02 to 0.53+/-0.01 (P = 0.003). Follow-up was
      100% complete and ranged from 3 months to 10 years. There were no early or late
      deaths. All patients were asymptomatic with complete closure of CAF except 1
      patient (5%) who had a recurrence of shunt at 6-month follow-up, which was re
      closed by percutaneous technique. CONCLUSION: Transcatheter closure of CAF is
      feasible and safe in anatomically suitable vessels and is a promising alternative
      to surgery in most patients.

PMID- 19743491
TI  - Oxygen therapy-use and abuse in acute myocardial infarction patients.
AB  - In August 2008, an article was published in Heart entitled, "The Routine Use of
      Oxygen in the Treatment of Myocardial Infarction." This article stimulated me to
      opine on this topic, which has been an interest of mine for many years.

PMID- 19743492
TI  - Infectious thoracic aortitis: a literature review.
AB  - Infectious thoracic aortitis (IA) remains a rare disease, especially after the
      appearance of antibiotics. However, if left untreated it is always lethal. It
      usually affects patients with atherosclerotic aortic disease and/or infective
      endocarditis. Mycotic aneurysm is the most common form of presentation, although
      a few reports of nonaneurysmal infectious thoracic aortitis have also been
      described. Various microorganisms have been associated with infectious thoracic
      aortitis, most commonly Staphylococcal, Enterococcus, Streptococcus, and
      Salmonella species. It is extremely important to establish an early diagnosis of
      IA, because this condition is potentially life-threatening. However, diagnosis is
      frequently delayed since clinical manifestations are usually nonspecific.
      Antibiotherapy in combination with complete surgical excision of the infected
      aorta is the best choice of treatment.

PMID- 19743493
TI  - Evolving cardiovascular disease prevalence, mortality, risk factors, and the
      metabolic syndrome in China.
AB  - The rapid growth transformation of China from a rural agrarian society to an
      industrial society with increased wealth has impacted the cardiovascular health
      of the entire population. The increasing prevalence of cardiovascular disease
      (CVD) and CVD risk factors mirror in some regards the disease prevalence in
      western industrialized countries and in other areas present unique public health
      issues. This article reviewed recent population surveys, reports, and clinical
      trials conducted in China. It was found that the prevalence of CVD and many of
      the risk factors such as hypertension, obesity, and diabetes contributing to
      disease mortality are increasing in China. However, compared with the United
      States, disease mortality is lower. Also, cerebrovascular disease is far more
      common than ischemic heart disease in China. The low prevalence of disease may
      suggest a reduced role of diagnostic imaging studies as compared with the US,
      while the increased percentage of strokes may point to the need for widely
      available emergent computed tomography (CT) imaging in hospitals in China. This
      article also discusses the occurrence of metabolic syndrome, obesity, glucose
      intolerance, diabetes, and their unique features in the Chinese population. Of
      interest, compared with the Caucasian cohort of the same body mass index (BMI),
      the Chinese had a higher percentage of body fat. Metabolic syndrome was found to
      be associated with increased cardiovascular mortality rate. With one fifth of the
      world's population, China can anticipate a dramatic rise, in absolute numbers, of
      CVD. It is imperative that national and regional programs are initiated to detect
      and treat the disease.

PMID- 19743494
TI  - Hemodynamics, diuretics, and nesiritide: a retrospective VMAC analysis.
AB  - HYPOTHESIS: Hypotension has been proposed as the cause of nesiritide-associated
      increases in serum creatinine (SCr); however, this hypothesis has not been
      tested. METHODS: This retrospective evaluation of patients who had a pulmonary
      artery catheter and received nesiritide in the Vasodilation in the Management of
      Acute Congestive Heart Failure (VMAC) trial assessed hypotension, SCr elevation,
      concomitant therapy, and mortality. Patients were categorized by baseline
      pulmonary capillary wedge pressure (PCWP) and analyzed both for overall
      population and by diuretic dose. RESULTS: Compared with patients with PCWP > 23
      mm Hg (n = 105), patients with PCWP < or = 23 mm Hg (n = 49) had more hypotension
      within 24 hours of initiating nesiritide (16% vs 7%), but neither more SCr
      elevation by nominal day 30 (29% vs 28%) nor higher mortality (30 days: 8.2% vs
      7.7%; 6 months: 29.0% vs 29.3%). The risk of hypotension was directly related to
      high dose diuretics (25% vs 6%; relative risk [RR]: 4.2; 95% confidence interval
      [CI]: 1.10-15.82) and was not significantly increased in patients without this
      concomitant treatment (10% vs 7%; RR: 1.4; 95% CI: 0.34-5.93). Additionally, high
      dose diuretics significantly increased the risk of SCr elevation (RR: 2.6; 95%
      CI: 1.03-6.64) and 6 month mortality (hazard ratio: 3.6; 95% CI: 1.19-10.63) in
      patients with PCWP < or = 23 mm Hg. CONCLUSIONS: Hypotension is not the primary
      etiology for nesiritide-associated increases in SCr. High dose diuretics increase
      the risk of adverse outcomes in patients with PCWP < or = 23 mm Hg and should be
      reserved for patients in whom PCWPs are known to be markedly elevated.

PMID- 19743495
TI  - Early treatment for non-ST-segment elevation acute coronary syndrome is
      associated with appropriate discharge care.
AB  - BACKGROUND: Acute treatment is associated with improved in-hospital outcomes for
      patients with non-ST-segment elevation acute coronary syndrome (NSTE ACS).
      HYPOTHESIS: Patients who receive appropriate acute treatment are more likely to
      receive guideline-recommended therapy at hospital discharge. METHODS: Use of
      aspirin (ASA), beta-blockers, and clopidogrel was evaluated in the first 24 hours
      and upon hospital discharge according to the 2002 American College of
      Cardiology/American Heart Association (ACC AHA) guidelines for NSTE ACS. We
      compared the relationship between 3 groups: (1) ASA therapy given in the
      emergency department (ED); (2) ASA therapy not given in the ED, but within the
      first 24 hours; and (3) no acute ASA treatment. The ASA data set includes 10,468
      high risk patients with positive cardiac biomarkers or ischemic ST-segment
      changes on ECG from the Can Rapid Risk Stratification of Unstable Angina Patients
      Suppress Adverse Outcomes with Early Implementation of the ACC/AHA Guidelines
      (CRUSADE) Quality Improvement Initiative. Beta-blocker therapy was evaluated in
      11,838 and clopidogrel treatment in 17,513 patients presenting to over 345 US
      hospitals. RESULTS: Patients who received acute ASA in the ED, ASA in the first
      24 hours but not in the ED, and patients who did not receive ASA therapy within
      24 hours had discharge ASA treatment rates of 91.8%, 91.4%, and 55.6%,
      respectively (P < 0.0001). Patients eligible for beta-blocker and clopidogrel
      therapy had discharge beta-blocker treatment rates of 91.1%, 92.4%, and 46.6% (P
      < 0.0001), and discharge clopidogrel treatment rates of 86.6%, 92.4%, and 38.5%
      (P < 0.0001), respectively. CONCLUSIONS: Acute treatment for NSTE ACS in-hospital
      is associated with appropriate treatment on hospital discharge. This link between
      early treatment and discharge therapy may lead to new approaches ensuring the
      delivery of high-quality, guideline-based care for patients with NSTE ACS.

PMID- 19743496
TI  - The usage patterns of cardiac bedside markers employing point-of-care testing for
      troponin in non-ST-segment elevation acute coronary syndrome: results from
      CRUSADE.
AB  - BACKGROUND: Point-of-care (POC) testing may expedite the care of emergency
      department (ED) patients suspected of having acute coronary syndromes (ACS). We
      evaluated the use patterns of cardiac bedside markers or POC testing for troponin
      in patients with non-ST-segment elevation (NSTE) ACS. METHODS: NSTE ACS data were
      collected from the Can Rapid Risk Stratification of Unstable Angina Patients
      Suppress Adverse Outcomes with Early Implementation of the American College of
      Cardiology/American Heart Association (ACC/AHA) Guidelines (CRUSADE) registry. We
      compared hospital and patient characteristics, in-hospital events, and process-of
      care variables between hospitals to those that did not use POC testing in > or =
      50% of enrolled patients. We examined characteristics, in-hospital events, and
      process-of-care differences between patients with negative vs positive troponin
      POC testing results. RESULTS: Of 568 hospitals, 74 (16,276 patients) had high POC
      usage compared with 197 hospitals (50,782 patients) with no troponin POC usage.
      From the high POC usage hospitals, 12,604 patients had recorded troponin POC test
      results. Hospitals with high POC usage had a shorter ED length of stay and were
      less likely to administer aspirin, beta-blockers, and heparin during the first 24
      hours of care. Patients with positive troponin POC results were more often older,
      minority, female, Medicare-insured, diabetic, and renally impaired. They had
      fewer electrocardiograms within 10 minutes but were more likely to get aspirin,
      beta-blockers, glycoprotein IIb/IIIa inhibitors, and heparin within 24 hours of
      arrival. They also had longer ED lengths of stay, received fewer in-hospital and
      interventional procedures, and had more adverse clinical events. CONCLUSION:
      Differences existed in how hospitals used POC testing and the care given based on
      those results. Positive POC results are associated with expedited and higher use
      of anti-ischemic therapies.

PMID- 19743497
TI  - Angiotensin receptor blocker therapy for heart failure patients: is combination
      treatment a feasible prospect?
AB  - BACKGROUND: The addition of the angiotensin II type 1 receptor blocker (ARB)
      candesartan to a angiotensin-converting enzyme inhibitor (ACEI) has been
      associated with improved clinical outcomes in patients with heart failure.
      However many do not tolerate combination therapy and concerns have been raised
      regarding excessive neurohormonal inhibition. HYPOTHESIS: The majority of
      patients with chronic heart failure are not eligible or do not tolerate
      combination therapy with an ACEEI and ARB. METHODS: We prospectively evaluated
      115 consecutive patients with heart failure (median age 74 y; 74% males; mean
      left ventricular ejection fraction 30%) within a district general hospital for
      eligibility and tolerance to combination therapy using candesartan in addition to
      recommended doses of an ACEI. RESULTS: Overall, 109 (95%) were ineligible to
      initiate candesartan. The most frequent reasons were that, despite best efforts
      at optimization, 77% of patients were unable to achieve recommended doses of an
      ACEI, 29% were relatively asymptomatic, 20% had symptomatic hypotension, and 35%
      were already taking an ARB due to previous ACEI "intolerance." Overall, 6 (5%) of
      patients satisfied the eligibility criteria of whom 3 (3% of total) were already
      taking "optimal" doses of an ARB in addition to an ACEI. The remaining 3 patients
      commenced the titration schedule with candesartan. All 3 patients failed the
      first titration phase (4 mg once daily) within 2 weeks of initiation, due to the
      development of hyperkalemia. CONCLUSIONS: The use of combination therapy with an
      ARB in addition to recommended doses of ACEI does not appear feasible in patients
      with heart failure in the general population, as the vast majority are not
      eligible.

PMID- 19743498
TI  - Brugada-like electrocardiographic pattern due to hyperkalemia.

PMID- 19743499
TI  - Apolipoprotein measurements: is more widespread use clinically indicated?
AB  - Apolipoprotein (apo) B may be a more sensitive measure of atherogenicity than low
      density lipoprotein cholesterol (LDL-C) and a better index for assessing
      cardiovascular risk. The refined risk assessment provided by apo B may be
      important in patients at high cardiometabolic risk such as those with diabetes
      mellitus or metabolic syndrome, as these conditions are often associated with
      normal LDL-C values but increased numbers of small, dense low-density lipoprotein
      (LDL) particles (indicating increased levels of apo B). Although apo B is not
      currently a treatment target in the United States cholesterol-lowering
      guidelines, a consensus conference endorsed by the American Diabetes Association
      and the American College of Cardiology recently recommended that apo B be added
      as a therapeutic target in patients at high cardiometabolic risk and in patients
      with clinical cardiovascular disease or diabetes. Suggested target goals are < 90
      for high risk and < 80 mg/dL for highest risk patients. Current clinical data
      indicate that intensive statin therapy can lower apo B to meet this aggressive
      goal. While the proatherogenic/antiatherogenic ratio of apo B/apo A-I is a better
      risk discriminator than the single proatherogenic measurement (apo B), clinical
      trial data are lacking regarding the impact of increasing apo A-I and high
      density lipoprotein on outcomes.

PMID- 19743500
TI  - Combined use of pharmacokinetic modeling and a steady-state delivery approach
      allows early assessment of IkappaB kinase-2 (IKK-2) target safety and efficacy.
AB  - NF-kappaB activation is clearly linked to the pathogenesis of multiple
      inflammatory diseases including arthritis. The prominent role of IkappaB kinase-2
      (IKK-2) in regulating NF-kappaB signaling in response to proinflammatory stimuli
      has made IKK-2 a primary anti-inflammation therapeutic target. PHA-408, a potent
      and selective IKK-2 inhibitor, was identified internally and used for our studies
      to assess this target. In early in vivo studies, PHA-408 demonstrated efficacy at
      high doses; however, the correlation between PHA-408 exposure and efficacy could
      not be established using standard dosing paradigms for the rat disease models.
      Similar concerns arose from early in vivo safety studies where appropriate NOAEL
      margins were not achieved. Following a full investigation of the physicochemical
      properties of the molecule and pharmacokinetic modeling, an oral steady-state
      delivery strategy was designed to administer PHA-408 to the rat for both efficacy
      and safety studies. Using this steady-state delivery, a clear dose-response
      relationship was established between plasma concentrations of PHA-408 and
      efficacy in the rat arthritis model. The same steady-state delivery approach was
      used to demonstrate the target safety. In summary, a combination of
      pharmacokinetic modeling with a steady-state delivery approach allowed us to
      establish confidence in both the mechanism and safety of the target.

PMID- 19743501
TI  - Role of pellet size, shape, and filling method in achieving fill weight
      uniformity for encapsulated pelletized systems: a comparison of experiment and
      computer simulation.
AB  - Correlations between experimental filling and computer simulation for real
      pelletized systems were evaluated in this study. Simulations were successful in
      predicting the fill weight variability of a variety of pellet sizes and shapes
      and demonstrated similar values and trends to those observed experimentally.
      Simulation also helped identifying the critical variables affecting filling
      consistency such as pellet attributes and filling methods. Unit filling and
      automatic filling were found to be more comparable to simulation whilst manual
      flood filling appeared to lack reproducibility. Computer simulation can therefore
      be used as a method for predicting fill weight variability for different pellet
      fractions filled using different filling methods, which can facilitate process
      control and assurance of product quality.

PMID- 19743502
TI  - Mechanisms of membrane transport of poorly soluble drugs: role of micelles in
      oral absorption processes.
AB  - Micelles formed in the GI tract by bile acid and lecithin play an important role
      in oral absorption of poorly soluble drugs. In this situation, the drug molecules
      are present in equilibrium between the free and micellar states. In this study,
      the relationship between the free drug concentration and the membrane
      permeability of poorly soluble drugs was examined. Permeability across a Caco-2
      monolayer and a dialysis membrane were measured in a side-by-side chamber system.
      The concentrations of sodium taurocholate (NaTC) and lecithin were varied to
      allow measurement of membrane permeability at different concentrations of free
      drugs. For troglitazone, hexylparaben, and heptylparaben, an increase in the NaTC
      and lecithin concentrations caused the permeability across the Caco-2 monolayer
      to decrease slightly, whereas the permeability across the dialysis membrane
      decreased markedly. In contrast, the changes in permeability of griseofulvin with
      an increased micelle concentration were similar for the Caco-2 monolayer and the
      dialysis membrane. Assuming that the permeability for the dialysis membrane
      reflects the free drug concentration in the medium, these results suggest that
      troglitazone and alkylparabens, but not griseofulvin, can partition directly from
      micelles to Caco-2 monolayers. This mechanism may contribute to oral absorption
      of drugs that are poorly soluble in water.

PMID- 19743503
TI  - Pharmacokinetics and immunoglobulin response of subcutaneous and intravenous
      atacicept in patients with systemic lupus erythematosus.
AB  - Atacicept, a recombinant fusion protein of the TACI receptor and human IgG, is an
      inhibitor of B-Lymphocyte Stimulator (BLyS) and APRIL, potent stimulators of B
      cell maturation, proliferation, and survival. Pharmacokinetics (PKs) and
      biological activity of intravenous (iv) and subcutaneous (sc) atacicept are
      described here for patients with systemic lupus erythematosus in two randomized,
      double-blind, placebo-controlled, Phase Ib studies. Study 1: Six cohorts of eight
      patients received sc atacicept (single dose: 0.3, 1, 3, or 9 mg/kg; four weekly
      doses: 1 or 3 mg/kg), or placebo (3:1 ratio). Study 2: Four cohorts of six
      patients received iv atacicept (single dose: 3, 9, or 18 mg/kg; multiple dose: 2
      x 9 mg/kg), or matching placebo (5:1 ratio). PK profiles were determined through
      serum atacicept and atacicept-BLyS complex, and biological activity through IgA,
      IgG, and IgM levels. PK profiles of atacicept were influenced by saturable
      binding between atacicept and its ligands, and were consistent and predictable
      across doses and regimens. Atacicept's biological activity was compatible with
      its presumed mechanism of action. Bioavailability was approximately 30-40%
      following sc or iv administration and similar doses yielded similar biological
      activity irrespective of administration route. This observation may have a
      mechanistic foundation and may inform dosing regimen design for future studies.

PMID- 19743504
TI  - Degradation of paclitaxel and related compounds in aqueous solutions III:
      Degradation under acidic pH conditions and overall kinetics.
AB  - Paclitaxel and related taxanes are complex molecules with numerous hydrolysable
      ester groups, possible epimerization at the 7-position, and possessing a strained
      oxetane ring, a possible site for acid-catalyzed cleavage. Presented here is the
      stability of paclitaxel, 10-deacetylbaccatin III, baccatin III, and N-benzoyl-3
      phenylisoserine ethyl ester in aqueous solution over a pH range of 1-5 at various
      temperatures. Analysis of various samples was by HPLC-UV and LC-MS. Baccatin III,
      10-deacetylbaccatin III, and N-benzoyl-3-phenylisoserine ethyl ester were found
      to undergo acid catalysis since pH-rate profiles all followed a first-order
      dependency in hydrogen ion concentration. No evidence of any epimerization was
      noted at acidic pH values. Baccatin III and 10-deacetylbaccatin III showed
      similar degradation rates with possible products being possible dehydration
      around the 13-hydroxy group and cleavage of the oxetane ring. Cleavage of the 10
      acetyl group of baccatin III was a minor initial pathway. N-Benzoyl-3
      phenylisoserine ethyl ester degraded significantly slower than both 10
      deacetylbaccatin III and baccatin III. At pH 2, paclitaxel degraded at a rate
      between that of N-benzoyl-3-phenylisoserine ethyl ester and 10-deacetylbaccatin
      III. The pH of maximum stability for all compounds appeared to be around pH 4.

PMID- 19743505
TI  - Exposure-dependent increases in IL-1beta, substance P, CTGF, and tendinosis in
      flexor digitorum tendons with upper extremity repetitive strain injury.
AB  - Upper extremity tendinopathies are associated with performance of forceful
      repetitive tasks. We used our rat model of repetitive strain injury to study
      changes induced in forelimb flexor digitorum tendons. Rats were trained to
      perform a high repetition high force (HRHF) handle-pulling task (12 reaches/min
      at 60 +/- 5% maximum pulling force [MPF]), or a low repetition negligible force
      (LRNF) reaching and food retrieval task (three reaches/min at 5 +/- 5% MPF), for
      2 h/day in 30 min sessions, 3 days/week for 3-12 weeks. Forelimb grip strength
      was tested. Flexor digitorum tendons were examined at midtendon at the level of
      the carpal tunnel for interleukin (IL)-1beta, neutrophil, and macrophage influx,
      Substance P, connective tissue growth factor (CTGF), and periostin-like factor
      (PLF) immunoexpression, and histopathological changes. In HRHF rats, grip
      strength progressively decreased, while IL-1beta levels progressively increased
      in the flexor digitorum peritendon (para- and epitendon combined) and endotendon
      with task performance. Macrophage invasion was evident in week 6 and 12 HRHF
      peritendon but not endotendon. Also in HRHF rats, Substance P immunoexpression
      increased in week 12 peritendon as did CTGF- and PLF-immunopositive fibroblasts,
      the increased fibroblasts contributing greatly to peritendon thickening.
      Endotendon collagen disorganization was evident in week 12 HRHF tendons. LRNF
      tendons did not differ from controls, even at 12 weeks. Thus, we observed
      exposure-dependent changes in flexor digitorum tendons within the carpal tunnel,
      including increased inflammation, nociceptor-related neuropeptide
      immunoexpression, and fibrotic histopathology, changes associated with grip
      strength decline.

PMID- 19743506
TI  - Improving bone density at the rotator cuff footprint increases supraspinatus
      tendon failure stress in a rat model.
AB  - The purpose of this study was to investigate whether supraspinatus tendon failure
      stress at the footprint can increase by improving the bone density at the rotator
      cuff footprint in a rat model. Bilateral ovariectomies were performed in twenty
      four 4-month-old Sprague-Dawley rats. Half received bisphosphonate (zoledronic
      acid) and the other half received no treatment (OVX + ZOM and OVX, respectively).
      Twelve additional rats did not undergo ovariectomy or receive bisphosphonate
      treatment (CON). All rats were sacrificed at 7 months of age. Quantitative micro
      computed tomography was used to assess bone density in the proximal humerus. A
      series of stress-relaxation tests were performed to assess stiffness and failure
      stress of the supraspinatus tendon. Bone density in OVX + ZOM was significantly
      higher at the rotator cuff footprint when compared to CON and OVX rats (p <
      0.0001). The supraspinatus tendons in the OVX group were significantly stiffer
      when compared to the CON and OVX + ZOM groups (p < 0.05). The failure stress of
      the OVX + ZOM group was significantly greater than the CON and OVX groups (22.89
      +/- 4.43 MPa vs. 18.36 +/- 3.16 and 17.70 +/- 4.92, respectively). In conclusion,
      improving the bone density at the rotator cuff footprint enhances failure stress
      of the suprapinatus tendon.

PMID- 19743507
TI  - Porous tantalum and poly-epsilon-caprolactone biocomposites for osteochondral
      defect repair: preliminary studies in rabbits.
AB  - Currently, various techniques are in use for the repair of osteochondral defects,
      none of them being truly satisfactory and they are often two step procedures.
      Comorbidity due to cancellous bone harvest from the iliac crest further
      complicates the procedure. Our previous in vitro studies suggest that porous
      tantalum (TM) or poly-epsilon-caprolactone scaffolds (PCL) in combination with
      periosteal grafts could be used for osteochondral defect repair. In this in vivo
      study, cylindrical osteochondral defects were created on the medial and lateral
      condyles of 10 rabbits and filled with TM/periosteum or PCL/periosteum
      biosynthetic composites (n = 8 each). The regenerated osteochondral tissue was
      then analyzed histologically, and evaluated in an independent and blinded manner
      by five different observers using a 30-point histological score. The overall
      histological score for PCL/periosteum was significantly better than for
      TM/periosteum. However, most of the regenerates were well integrated with the
      surrounding bone (PCL/periosteum, n = 6.4; TM/periosteum, n = 7) along with
      partial restoration of the tidemark (PCL/periosteum, n = 4.4; TM/periosteum, n =
      5.6). A cover of hyaline-like morphology was found after PCL/periosteum treatment
      (n = 4.8), yet the cartilage yields were inconsistent. In conclusion, the applied
      TM and PCL scaffolds promoted excellent subchondral bone regeneration. Neo
      cartilage formation from periosteum supported by a scaffold was inconsistent.
      This is the first study to show in vivo results of both PCL and TM scaffolds for
      a novel approach to osteochondral defect repair.

PMID- 19743508
TI  - Assessment drives learning: an unavoidable truth?
AB  - The debate around which factors drive medical students' learning is ongoing and
      controversial. What is the influence of an assessment's weighting on the
      motivation of students to study the particular subject? One medical school in
      London is in a unique position to investigate this question. At our institution,
      the weighting of Anatomy within the overall scheme of assessment has changed
      twice in recent years, a trend of increased weighting. This enabled a comparative
      investigation into the effect these changes have had on the students' motivation
      to learn Anatomy. A five-point Likert-scale questionnaire survey was used to
      evaluate students. A section within a broad survey of Anatomy teaching and
      learning at our institution was dedicated to the evaluation of the amount of
      weighting Anatomy received within the assessment structure and the effect this
      had on students' motivation toward learning the subject. Increasing Anatomy's
      weighting within the scheme of assessment produced a dramatic increasing trend
      toward students' motivation to learn Anatomy. The weighting of Anatomy has a
      profound effect on students' motivation to learn it. Although multifactorial and
      complex in nature, medical students' self-reported drive to study a subject is
      directly influenced by the weighting of the subject in the overall scheme of
      assessment.

PMID- 19743509
TI  - Keeping dissection alive for medical students.
AB  - Traditional dissection teaching is being reduced in a number of medical schools,
      particularly in the United Kingdom. In response to this, 12 medical students from
      Warwick University, UK, traveled to the Island of Grenada for an intensive
      extracurricular dissection course at St. George's University. This course not
      only benefited the host university through the creation of prosections for
      teaching but also allowed the participants to completely immerse themselves in
      anatomical study, by developing their dissection skills and consolidating
      anatomical knowledge. We believe that similar courses could be easily implemented
      by other medical schools, thereby allowing future students to keep traditional
      dissection alive.

PMID- 19743510
TI  - Gentamicin-impregnated chitosan/nanohydroxyapatite/ethyl cellulose microspheres
      granules for chronic osteomyelitis therapy.
AB  - In this article gentamicin (GM) impregnated microspheres were used to extend the
      drug release time for the treatment of chronic osteomyelitis. The granules were
      prepared in solution and consisted of nanohydroxyapatite (nHA), chitosan (CS) and
      GM loaded ethyl cellulose (EC) microspheres. A rabbit model with chronic
      osteomyelitis was made by using staphylococcus aureus and morrhuate sodium and
      special inspection methods were used to test the curative effects of the
      granules, such as microbiological investigations, tissue, and X-ray observations.
      The granules were provided with excellent drug release properties, 49 days in
      vitro and 45 days in vivo, moreover, they showed almost no cytotoxic for
      fibroblast and osteoblast. The findings indicated that the GM-impregnated
      CS/nHA/EC microspheres granules showed outstanding curative effect. Generally, it
      can be concluded that the granules containing GM impregnated microspheres may be
      used effectively in the treatment of the chronic osteomyelitis.

PMID- 19743511
TI  - In vitro and in vivo platelet targeting by cyclic RGD-modified liposomes.
AB  - Cell-selective delivery using ligand-decorated nanoparticles is a promising
      modality for treating cancer and vascular diseases. We are developing liposome
      nanoparticles surface-modified by RGD peptide ligands having targeting
      specificity to integrin GPIIb-IIIa. This integrin is upregulated and stimulated
      into a ligand-binding conformation on the surface activated platelets. Activated
      platelet adhesion and aggregation are primary events in atherosclerosois,
      thrombosis, and restenosis. Hence, platelet-targeted nanoparticles hold the
      promise of vascular site-selective delivery of drugs and imaging probes. Here, we
      report in vitro and ex vivo microscopy studies of platelet-targeting by liposomes
      surface-modified with a cyclic RGD peptide. The peptide-modified liposomes were
      labeled either with a lipophilic fluorophore or with lipid-tethered Nanogold(R).
      For in vitro tests, coverslip-adhered activated human platelets were incubated
      with probe-labeled liposomes, followed by analysis with fluorescence microscopy,
      phase contrast microscopy, and scanning electron microscopy (SEM). For in vivo
      tests, the liposomes were introduced within a catheter-injured carotid artery
      restenosis model in rats and post-euthanasia, the artery was imaged ex vivo by
      fluorescence microscopy and SEM. All microscopy results showed successful
      platelet-targeting by the peptide-modified liposomes. The in vitro SEM results
      also enabled visualization of nanoscopic liposomes attached to activated
      platelets. The results validate our nanoparticle design for site-selective
      vascular delivery.

PMID- 19743512
TI  - Friction properties of novel PVP/PVA blend hydrogels as artificial cartilage.
AB  - In this work, novel polyvinylpyrrolidone (PVP)/polyvinylalcohol (PVA) blend
      hydrogels were prepared by repeated freezing-thawing cycles. The factors that
      influenced friction properties of blend hydrogels, such as PVP content, contact
      load, sliding speed, and lubrication condition, were mainly studied by sliding
      with stainless steel ball. The results showed that friction coefficients of the
      PVP/PVA blend hydrogels were definitely dependent on such influence factors. The
      friction system consisting of blend hydrogel and stainless steel ball nearly
      exhibited a mixed lubrication regime especially under bovine serum lubrication,
      and it can be proposed as a promising method to reduce wear of the prosthesis.

PMID- 19743513
TI  - Medical and psychiatric problems among men and women in a community corrections
      residential setting.
AB  - Though the medical and mental health morbidity of incarcerated offenders has been
      discussed in a number of recent reports, very few data have been published
      concerning medical and mental health problems facing those on community
      corrections supervision. In this study of community corrections offenders
      utilizing residential facilities, we found that frequencies of substance use
      disorders, other mental health disorders, and medical problems exceeded
      frequencies found in the community and, in some cases, were higher than
      frequencies found in incarcerated individuals. Of particular concern were the
      high frequencies of substance use disorders, traumatic brain injury, anxiety
      states, suicidal ideation, and prior self-harm. While the level of self-reported
      medical and mental health service utilization was higher than expected, it
      appeared low relative to the disease burden reported by this special population.
      We conclude that concurrent evaluation and treatment of medical and psychiatric
      problems during the process of community supervision is indicated in this
      population.

PMID- 19743514
TI  - Malingering in a correctional setting: the use of the Structured Interview of
      Reported Symptoms in a jail sample.
AB  - The ability to detect malingering in the correctional setting is of paramount
      importance. The burgeoning jail and prison population combined with statutory
      requirements for the provision of mental health treatment require that only those
      most in need receive these services. Several structured assessments have been
      developed to assist in the identification of individuals more likely to be
      feigning psychiatric symptoms. Prior to the development of these specialized
      assessments, subscales of standard psychological tests were used as an indicator
      of assessment attitudes, for both malingering and other dissimulation. At the
      Sacramento County (CA) Jail, the Structured Interview of Reported Symptoms (SIRS)
      is routinely administered when clinicians feel there is a possibility that an
      inmate receiving psychiatric services may be feigning or exaggerating his/her
      symptoms. Our study examined data from these evaluations of inmates in
      conjunction with other clinical data (e.g., psychiatric diagnosis, educational
      level) to determine those factors most associated with malingering in jail
      inmates. Our results indicate that the prevalence of malingering in our sample
      was quite high: over 66% were found to be malingering based on the scoring
      criteria for the SIRS. Inmates diagnosed with Antisocial Personality Disorder
      were no more likely to feign symptoms than inmates without this diagnosis.
      Inmates designated as malingering in their charts were no more likely to be found
      malingering on the SIRS, suggesting that they may have adopted an effective
      strategy.

PMID- 19743515
TI  - Adjuvant chemotherapy in lacrimal gland adenoid cystic carcinoma.

PMID- 19743516
TI  - Treatment of children with acute promyelocytic leukemia: results of the first
      North American Intergroup trial INT0129.
AB  - BACKGROUND: This report focuses on the children enrolled on the first North
      American Intergroup study of APL (INT0129). This study was designed to compare
      the rates of CR, disease-free survival (DFS), overall survival (OS) and toxicity
      of therapy with all-trans-retinoic acid (ATRA) for remission induction and/or
      maintenance compared to conventional chemotherapy in patients with previously
      untreated APL. PROCEDURE: Fifty-three patients who were documented to have the
      t(15;17) translocation were able to be evaluated for toxicity of treatment,
      outcome of induction, and survival. RESULTS: The overall CR rate was 81%. The
      estimated 5-year DFS from time of CR was 41% for all patients. The estimated 5
      year OS for all patients from entry into the study was 69%. The 5-year DFS from
      time of CR for patients who were randomized to ATRA for induction or maintenance
      or both was 48% compared to 0% for patients who never received ATRA (P < 0.0001).
      CONCLUSIONS: The most important finding of our study is that a significant DFS
      advantage exists for children with APL who received ATRA during induction or
      maintenance or both compared to children who received no ATRA. Furthermore,
      remissions in these children appear durable as the OS rates are stable at 10
      years.

PMID- 19743517
TI  - Factors affecting the delivery of family-centered care in pediatric oncology.
AB  - BACKGROUND: The provision of family-centered care (FCC) emphasizes a partnership
      between parents and health-care providers so that families are involved in every
      aspect of services for their child. Our study examines factors related to
      parental perception of the family-centeredness of pediatric oncology services.
      PROCEDURE: This Canadian multi-institutional cross-sectional study included
      children with cancer receiving active treatment. One parent from each family
      provided information about the child, parent/family demographics, diagnosis, and
      treatment. FCC was measured with the MPOC-20, a valid and reliable tool in the
      pediatric oncology setting that consists of two subscales: "Family-Centered
      Service" and "Providing General Information." Logistic multiple regression
      analyses were used to identify factors that were associated with lower ratings of
      FCC for each subscale. RESULTS: Completed questionnaires were received back from
      411 parents, giving an overall response rate of 80%. Worse perceived prognosis
      and worse parental psychosocial health were associated with less favorable
      ratings for both MPOC-20 subscales. In addition, parents who were not married or
      living common-law scored lower ratings for the Family-Centered Services subscale,
      whereas scores for the Provision of General Information subscale differed
      depending on the treatment facility at which the child received care.
      CONCLUSIONS: Our study identified child/parent factors and health-care delivery
      factors associated with FCC provided in the pediatric oncology setting. These
      results could be used as the starting point for future research looking at
      optimization of the FCC process.

PMID- 19743518
TI  - Family, demographic and illness-related determinants of HRQL in children with
      brain tumours in the first year after diagnosis.
AB  - AIMS: To evaluate the relationship between parent- and child-report Health
      Related Quality of Life (HRQL) and demographic, tumour and family variables in
      children with a brain tumour in the first year after diagnosis and to identify
      determinants of HRQL at 12 months. PROCEDURE: Longitudinal prospective study:
      Semi-structured interviews took place approximately 1, 6 and 12 months after
      diagnosis. HRQL was measured using the self- and parent-report PedsQL 4.0 Total
      Scale Score. Tumour and treatment variables considered included tumour site and
      grade, hydrocephalus at diagnosis, chemotherapy and radiotherapy. Family
      variables included measures of family function, family support and family stress,
      the primary carer's coping strategies and symptoms of depression and anxiety.
      Univariate analyses were used at all three time points, and to identify potential
      early predictors of HRQL at 1 year. Regression analysis was then used to identify
      the most important determinants of HRQL at 1 year. RESULTS: Thirty-five patients
      completed the 12-month interviews. There were consistent significant negative
      correlations between concurrent family impact of illness and parent and self
      report HRQL, and positive correlations between concurrent family support and
      parent-report HRQL. Treatment with radio- or chemotherapy correlated with child
      report HRQL only at some time points. Multivariate analysis showed infratentorial
      tumour site, and poor HRQL at 1 month best predicted poor self- and parent-report
      HRQL at 12 months. CONCLUSION: Children with infratentorial tumours and poor HRQL
      early after diagnosis tend to have poor HRQL at 1 year. While family factors are
      important modulators of concurrent HRQL, they do not appear important in
      predicting HRQL.

PMID- 19743519
TI  - The impact of CD34+ cell dose on platelet engraftment in pediatric patients
      following unmanipulated haploidentical blood and marrow transplantation.
AB  - OBJECTIVE: Unmanipulated haploidentical blood and marrow transplantation has been
      developed as an alternative transplant strategy for pediatric patients with
      hematological diseases. The aim of this study was to investigate the effects of
      donor and recipient characteristics on hematopoietic recovery in pediatric
      patients following unmanipulated haploidentical transplantation. METHODS: Factors
      correlating with hematopoietic recovery in 133 pediatric patients after
      unmanipulated haploidentical transplantation were analyzed retrospectively.
      RESULTS: All patients reached an absolute neutrophil count of 500/microl in a
      median of 12 days (range, 9-49 days). One hundred thirty-three patients reached
      an untransfused platelet count of more than 20,000/microl in a median of 15 days
      (range, 7-180 days). Univariate analysis showed five factors associated with
      platelet engraftment. These were time to transplantation after diagnosis (P =
      0.072), infused nuclear cells/kg of recipient weight (P = 0.028), CD3+ cells/kg
      of recipient weight (P = 0.082), CD4+ cells/kg of recipient weight (P = 0.083),
      and CD34+ cells/kg of recipient weight (P = 0.012). Multivariate analysis showed
      that infused CD34+ cells/kg of recipient weight (CD34+ cells more than 2.42 x
      10(6)/kg vs. less than or equal to 2.42 x 10(6)/kg, HR = 1.733; 95% CI 1.222
      2.549; P = 0.002) were significantly associated with an increased risk of
      platelet engraftment. Patients receiving a CD34+ cell dose more than 2.42 x
      10(6)/kg had a short time [12 days (range, 7-176 days)] to achieve an
      untransfused platelet engraftment, compared to 18 days (range, 7-180 days) in
      patients receiving a lower dose (P < 0.001). CONCLUSIONS: Our results suggest
      that low number of CD34+ cells in allografts is a critical factor associated with
      delayed platelet engraftment after unmanipulated haploidentical transplantation
      in pediatric patients.

PMID- 19743520
TI  - Pathways to psychiatric care in European prison systems.
AB  - The aims of this study were to describe and analyse the concepts of provision of
      mental health services for prison inmates in 24 countries in the European Union
      and the EFTA. Data were gathered by means of a structured questionnaire that was
      completed by national experts in the participating countries. This article
      stresses the different organizational models of mental health care for inmates,
      different legal standards for screening their mental health status and different
      pathways to psychiatric care and aftercare. The study revealed serious
      shortcomings. Even the most rudimentary health reporting standards for mental
      health care in prison are lacking almost everywhere in Europe. Psychiatric
      screening and assessment procedures at prison entry and during imprisonment
      differ substantially and do not fulfil recognized quality standards. In many
      countries, the appointment of inadequately trained staff to perform such
      screenings increases considerably the risk that mental disorders or psychiatric
      needs of the inmates will remain undetected. Furthermore, the pathways to care in
      the case of an acute psychotic episode differ significantly, since referral to
      prison hospitals, medical prison wards, forensic hospitals, or general
      psychiatric hospital are used in various combinations depending on different
      national legal regulations and on the availability of services or other regional
      circumstances. Therefore, the collaborating experts place the quality of European
      prison mental health care into serious question.

PMID- 19743521
TI  - Conducting research in corrections: challenges and solutions.
AB  - Research in correctional settings has progressed from the exploitation of a
      vulnerable population in the years prior to 1978 to its current overly protective
      and restrictive state. With the considerable growth in the numbers of inmates
      with medical and mental health care needs, developing effective interventions to
      serve this population is paramount. There now appear to be signs of interest in
      and support for research with inmates by correctional agencies, academia, and
      health care organizations. Innes (2003) has articulated the following strategies
      for implementing research in prison: (1) gather stakeholders; (2) include one or
      more experienced research collaborators; (3) consider obtaining technical
      assistance from a university or the National Institute of Corrections (NIC); (4)
      define potential opportunities/interests that support the institution's mission;
      (5) develop a relationship with an IRB; (6) pilot a small proposal that is of
      interest and potential value to the organization. The authors illustrate the
      implementation of a study in a correctional system that uses these strategies.

PMID- 19743522
TI  - G-rich sequence-functionalized polystyrene microsphere-based instantaneous
      derivatization for the chemiluminescent amplified detection of DNA.
AB  - Herein, we develop a novel chemiluminescence (CL) approach with high sensitivity
      and excellent selectivity, by taking advantage of magnetic beads as
      preconcentration carriers and polystyrene microspheres as an amplification
      platform. Briefly, a 'sandwich-type' detection strategy is employed in our
      design, which involves capture probe DNA immobilized on the surface of carboxyl
      terminated magnetic beads and multiple biotinylated reporter DNA self-assembled
      on the surface of streptavidin-modified polystyrene microspheres. The reporter
      DNA includes a guanine nucleobase-rich (G-rich) sequence domain for the
      generation of light and an additional tethered nucleic acid domain complementary
      with the target DNA. The CL signal is obtained via a novel instantaneous
      derivatization reaction between a specific CL reagent and the guanine nucleo
      bases rich in the target and reporter DNA. As a result, we demonstrate that this
      DNA assay is reproducible, stable, easy to use, and can sensitively detect
      femtomolar target DNA related to anthrax lethal factors with excellent
      differentiation ability for single-base mismatched sequences. Overall, this new
      CL protocol couples the high sensitivity of CL analysis with effective magnetic
      separation for discriminating against unwanted constituents such as mismatched
      sequences, and hence, offers great promise for DNA hybridization analysis.

PMID- 19743523
TI  - Synthesis and luminescence properties of lanthanide complexes with a new tripodal
      ligands featuring salicylamide arms.
AB  - A series of luminescent lanthanide complexes with a new tripodal ligand featuring
      salicylamide arms, 2,2',2''-nitrilotris(2
      furfurylaminoformylphenoxy)triethylamine (L), were synthesized and characterized
      by elemental analysis, IR and molar conductivity measurements. Photophysical
      properties of the complexes were studied by means of UV-vis absorption and steady
      state luminescence spectroscopy. Excited-state luminescence lifetimes and quantum
      yield of the complexes were determined. Luminescence studies demonstrated that
      the tripodal ligand featuring salicylamide arms exhibits a good antennae effect
      with respect to the Tb(III) and Dy(III) ion due to efficient intersystem crossing
      and ligand to metal energy transfer. From a more general perspective, this work
      offers interesting perspectives for the development of efficient luminescent
      stains and enlarges the arsenal for developing novel luminescent lanthanide
      complexes of salicylamide derivatives.

PMID- 19743524
TI  - Luminescence studies on Ba2ZnSi2O7: Eu(2+) phosphors crystals.
AB  - A novel blue green-emitting phosphor, Ba2ZnSi2O7: Eu(2+), was prepared by
      combustion synthesis method and an efficient bluish green emission under from
      ultraviolet to visible light was observed. The emission spectrum shows a single
      intensive band centered at 503 nm, which corresponds to the 4f(6)5d(1) -> 4f(7)
      transition of Eu(2+). The excitation spectrum is a broad band extending from 260
      to 465 nm, which matches the emission of ultraviolet light-emitting diodes (UV
      LEDs). The effect of doped Eu(2+) concentration on the emission intensity of
      Ba2ZnSi2O7: Eu(2+) was also investigated. The result indicates that Ba2ZnSi2O7:
      Eu(2+) can be potentially useful as a UV radiation-converting phosphor for white
      light-emitting diodes.

PMID- 19743525
TI  - Sensitive determination of gentiopicroside in medicine and bio-fluids using
      luminol-myoglobin chemiluminescence combined with flow injection technique.
AB  - A novel chemiluminescence method for the determination of gentiopicroside is
      presented, which was based on the inhibitory effect of gentiopicroside on the
      chemiluminescence reaction between luminol and myoglobin in a flow-injection
      system. The decrement of chemiluminescence intensity was linear with the
      logarithm of gentiopicroside concentration over the range from 10.0 pg mL(-1) to
      500.0 ng mL(-1) (r(2) = 0.9992), with a detection limit of 3.0 pg mL(-1)
      (3sigma). At a flow rate of 2.0 mL min(-1), a complete analytical process could
      be performed within 0.5 min, including sampling and washing, with a relative
      standard deviation of less than 3.0% (n = 5). The proposed procedure was applied
      successfully in the determination of gentiopicroside in pharmaceutical
      preparations, human urine and serum without any pretreatment procedure. The
      possible mechanism of the reaction was also discussed.

PMID- 19743526
TI  - Determination of protoberberine alkaloids in medicinal plants based on acidic
      potassium permanganate chemiluminescence system.
AB  - A simple method was established to determine protoberberine alkaloids in Cortex
      Phellodendri and Rhizoma Coptidis based on an acidic potassium permanganate
      chemiluminescence (CL) system. The optimum conditions for the CL reaction between
      protoberberine alkaloids and potassium permanganate were studied in detail. Under
      the optimum conditions, the linear response ranges for berberine, palmatine and
      jatrorrhizine were 0.038-7.27, 0.031-18.1 and 0.012-3.61 MUg/mL with detection
      limits of 0.005, 0.004 and 0.0007 MUg/mL, respectively. This method was
      successfully applied to determine the content of protoberberine alkaloids
      (calculated using berberine as an index) in Cortex Phellodendri and Rhizoma
      Coptidis. In addition, a possible mechanism of this CL reaction was proposed on
      the basis of the investigation of CL, UV and fluorescent spectra of
      protoberberine alkaloids in acidic solution containing potassium permanganate.

PMID- 19743527
TI  - Flow injection chemiluminescence determination of 6-mercaptopurine based on a new
      system of potassium permanganate-thioacetamide-sodium hexametaphosphate.
AB  - A novel chemiluminescence method for the determination of 6-mercaptopurine was
      established based on 6-mercaptopurine inhibition of the chemiluminescence
      emission of potassium permanganate-thioacetamide-sodium hexametaphosphate system.
      The peak height was proportional to log 6-mercaptopurine concentration in the
      range 7.0 * 10(-10) to 1.0 * 10(-7)  g/mL and the detection limit was 1.9 * 10(
      11)  g/mL (S/N = 3). The relative standard deviation was 1.5% for the
      determination of 8.0 * 10(-8)  g/mL 6-mercaptopurine (n = 11). The proposed
      sensor was successfully applied to the analysis of 6-mercaptopurine in human
      serum samples.

PMID- 19743528
TI  - Resonance Rayleigh-scattering spectral method for the determination of some
      aminoglycoside antibiotics using CdTe quantum dots as a probe.
AB  - A novel method is used for the determination of some aminoglycoside antibiotics
      (AGs) such as etimicin (ETM), isepamicin (ISP) and amikacin (AMK). It is based on
      the resonance Rayleigh scattering (RRS) intensities enhanced by AGs-induced CdTe
      quantum dots aggregation. Under the optimum conditions, the increments in RRS
      intensity were directly proportional to the concentration of AGs in certain
      ranges. At the same time, the second-order scattering, the frequency-doubling
      scattering and the frequency-trebling scattering intensities were also enhanced
      and their increments were proportional to the concentration of AGs. Among them,
      the RRS method had the highest sensitivity; the linear ranges and detection
      limits for ETM, ISP and AMK were 0.085-7.2, 0.0067-1.2, 0.017-6.0 and 0.025,
      0.0051, 0.0020 MUg mL(-1) . This method was applied to the measurement of AGs in
      human serum and urine with satisfactory results. In addition, the reaction
      mechanism and the reasons for the enhancement of RRS are discussed using
      fluorescence, RRS, transmission electron microscope technology and quantum
      chemistry method.

PMID- 19743529
TI  - An X- (X=I, Br)-triggered ring-opening cyclization of cyclopropenyl-substituted
      alkyl halides or mesylates: an efficient and highly regio- and stereoselective
      approach to (E)-haloalkylidene 4-7-membered cyclic compounds.
AB  - Polyfunctionalized (E)-haloalkylidene cyclic products were efficiently
      synthesized in moderate to excellent yields via a regio- and stereoselective X-
      (X= I or Br)-triggered ring- opening intramolecular trapping of cyclopropenes 1.
      The reaction can be used for construction of 4-7-membered products. The E
      stereoselectivity of the exo-C=C bond is very high. The carbon-halogen bond in
      the exo-C=C bond may further be elaborated to prepare differently substituted
      cyclic products with a stereodefined C=C bond.

PMID- 19743530
TI  - [Endoscopy in patients receiving anticoagulation therapy II].

PMID- 19743531
TI  - [Emergency department X-rays requested by physicians or nurses].

PMID- 19743533
TI  - RETRACTION: Modulation of the specific interaction of cardiolipin with cytochrome
      c by zwitterionic phospholipids in binary mixed bilayers: A (2)H- and (31)P-NMR
      Study.

PMID- 19743532
TI  - Laparoscopic sigmoid resection for diverticulitis decreases major morbidity
      rates: a randomized controlled trial.

PMID- 19743534
TI  - Rural hospital beats the odds in South Africa.

PMID- 19743535
TI  - Poultry, politics, and antibiotic resistance.

PMID- 19743536
TI  - The global and the local: changes at Groote Schuur Hospital.

PMID- 19743537
TI  - Introduction. Dietary assessment of micronutrient intakes: a European
      perspective.

PMID- 19743538
TI  - Nonlinear flow in karst formations.
AB  - The variation of effective hydraulic conductivity as a function of specific
      discharge in several 0.2-m and 0.3-m cubes of Key Largo Limestone was
      investigated. The experimental results closely match the Forchheimer equation.
      Defining the pore-size length scale in terms of Forchheimer parameters, it is
      demonstrated that significant deviations from Darcian flow will occur when the
      Reynolds number exceeds 0.11. A particular threshold model previously proposed
      for use in karstic formations does not show strong agreement with the data near
      the onset of nonlinear flow.

PMID- 19743539
TI  - [Where are we heading?].

PMID- 19743540
TI  - [Safety requires hard work and harsh imposition from the authorities].

PMID- 19743541
TI  - Asymmetric construction of nitrogen-containing [2.2.2] bicyclic scaffolds using N
      ( p-dodecylphenylsulfonyl)-2-pyrrolidinecarboxamide.
AB  - An organocatalyzed approach to enantioenriched isoquinuclidines and
      bicyclo[2.2.2]octanes via a p-dodecylphenylsulfonamide-modified proline catalyst
      has been developed. A series of aromatic imines have been explored for the
      formation of isoquinuclidines with high levels of enantioselectivity and
      diastereoselectivity, strongly favoring the exo product. A series of aliphatic
      imines has also been explored, which provide access to bicyclo[2.2.2]octanes
      through a novel mechanistic pathway in high levels of enantioselectivity and
      diastereoselectivity, favoring the endo product.

PMID- 19743542
TI  - B vitamins may be "silver bullet" for age-related macular degeneration. Daily
      supplementation with folic acid plus vitamins B6 and B12 may reduce risk of AMD
      by 35-40 percent.

PMID- 19743543
TI  - Ranolazine: new drug. Stable angina: not worth the risk.
AB  - (1) Betablockers such as atenolol are the first-line symptomatic treatment for
      stable angina. Calcium channel blockers such as verapamil and amlodipine are
      second-line alternatives; (2) Ranolazine is now authorized for symptomatic
      adjuvant treatment of angina in patients who are poorly controlled by a
      betablocker and/or a calcium channel blocker. Its mechanism of action is poorly
      understood; (3) In two randomised double-blind trials in respectively 565 and 823
      patients treated for 7 and 12 weeks, ranolazine (500 mg to 1000 mg twice a day),
      added to ongoing amlodipine therapy only provided a limited benefit, preventing
      less than one angina attack per week; (4) Comparative trials failed to show
      whether ranolazine has a clear-cut impact on mortality; (5) Ranolazine prolongs
      the QT interval in a dose-dependent manner and thus exposes patients to the risk
      of torsades de pointes. It is also associated with gastrointestinal disorders
      (constipation, nausea, vomiting) and dizziness; (6) Ranolazine is metabolised by
      the cytochrome P450 isoenzymes CYP 3A4 and CYP 2D6 and is also a P-glycoprotein
      substrate. There is therefore a high risk of pharmacokinetic interactions. There
      is also a risk of pharmacodynamic interactions with drugs that prolong the QT
      interval; (7) In practice, the efficacy of ranolazine in the prevention of angina
      attacks does not outweigh the risk of severe adverse effects.

PMID- 19743544
TI  - Position statement: Position of the NSC Committee on Alcohol and Other Drugs on
      the source code of evidential breath-alcohol analyzers.

PMID- 19743545
TI  - Angioneurotic oedema in dental patients.

PMID- 19743546
TI  - A modified hybrid prosthesis.

PMID- 19743547
TI  - A survey of biscuit consumption.

PMID- 19743548
TI  - The use of an obturator in the management of the Pierre Robin syndrome.

PMID- 19743549
TI  - The classification and use of precision attachments.

PMID- 19743550
TI  - Bridges: an analysis of failures.

PMID- 19743551
TI  - Does meditation enhance cognition and brain plasticity?
AB  - Meditation practices have various health benefits including the possibility of
      preserving cognition and preventing dementia. While the mechanisms remain
      investigational, studies show that meditation may affect multiple pathways that
      could play a role in brain aging and mental fitness. For example, meditation may
      reduce stress-induced cortisol secretion and this could have neuroprotective
      effects potentially via elevating levels of brain derived neurotrophic factor
      (BDNF). Meditation may also potentially have beneficial effects on lipid profiles
      and lower oxidative stress, both of which could in turn reduce the risk for
      cerebrovascular disease and age-related neurodegeneration. Further, meditation
      may potentially strengthen neuronal circuits and enhance cognitive reserve
      capacity. These are the theoretical bases for how meditation might enhance
      longevity and optimal health. Evidence to support a neuroprotective effect comes
      from cognitive, electroencephalogram (EEG), and structural neuroimaging studies.
      In one cross-sectional study, meditation practitioners were found to have a lower
      age-related decline in thickness of specific cortical regions. However, the
      enthusiasm must be balanced by the inconsistency and preliminary nature of
      existing studies as well as the fact that meditation comprises a heterogeneous
      group of practices. Key future challenges include the isolation of a potential
      common element in the different meditation modalities, replication of existing
      findings in larger randomized trials, determining the correct "dose," studying
      whether findings from expert practitioners are generalizable to a wider
      population, and better control of the confounding genetic, dietary and lifestyle
      influences.

PMID- 19743553
TI  - "Subtle" psychosomatic aspects of Tibetan medicine.
AB  - The theory and practice of traditional Tibetan medicine (TTM) is based on an
      understanding of a tri-level psycho-physical system; this bi-directional
      connection between the psycho-somatic realms is mediated by a distinct, yet
      inseparable energetic system--the subtle body. TTM practitioners approach both
      diagnosis and treatment from an understanding of this subtle energetic system. In
      the Tibetan yogic tradition, control of this system via advanced yogic and
      meditative technologies is the path to realize extraordinary levels of health,
      happiness, and longevity. As a result, understanding this intricately linked
      philosophical, medical, and yogic system is critical for engaging in dialogue
      about longevity-enhancement within this tradition.

PMID- 19743552
TI  - The inflammatory reflex and the role of complementary and alternative medical
      therapies.
AB  - The body's first defense against invading pathogens or tissue injury is the
      innate immune system. Since excessive immune responses can be damaging, anti
      inflammatory mechanisms function to control the pro-inflammatory response and
      prevent injury. The cholinergic anti-inflammatory pathway is a neural mechanism
      that suppresses the innate inflammatory response. Knowledge concerning
      innervation of the immune system offers a unique opportunity to explore
      previously unrecognized techniques to treat disease. It also enables
      consideration of the neurological basis of complementary and alternative medical
      therapies, such as meditation and acupuncture. This evolving area of research has
      implications for the pathogenesis of chronic inflammatory conditions including
      inflammatory bowel disease, rheumatoid arthritis, type 2 diabetes, and other
      conditions of excessive cytokine release.

PMID- 19743554
TI  - Optimizing learning and quality of life throughout the lifespan: a global
      framework for research and application.
AB  - This overview surveys the new optimism about the aging mind/brain, focusing on
      the potential for self-regulation practices to advance research in stress
      protection and optimal health. It reviews recent findings and offers a research
      framework. The review links the age-related biology of stress and regeneration to
      the variability of mind/brain function found under a range of conditions from
      trauma to enrichment. The framework maps this variation along a biphasic
      continuum from atrophic dysfunction to peak performance. It adopts the concept of
      allostatic load as a measure of the wear-and-tear caused by stress, and
      environmental enrichment as a measure of the use-dependent enhancement caused by
      positive reinforcement. It frames the dissociation, aversive affect and
      stereotyped reactions linked with stress as cognitive, affective and behavioral
      forms of allostatic drag; and the association, positive affect, and creative
      responses in enrichment as forms of allostatic lift. It views the human
      mind/brain as a heterarchy of higher intelligence systems that shift between a
      conservative, egocentric mode heightening self-preservation and memory and a
      generative, altruistic mode heightening self-correction and learning. Cultural
      practices like meditation and psychotherapy work by teaching the self-regulation
      of shifts from the conservative to the generative mode. This involves a systems
      shift from allostatic drag to allostatic lift, minimizing wear-and-tear and
      optimizing plasticity and learning. For cultural practices to speed research and
      application, a universal typology is needed. This framework includes a typology
      aligning current brain models of stress and learning with traditional Indo
      Tibetan models of meditative stress-cessation and learning enrichment.

PMID- 19743555
TI  - Toward a science of exceptional achievement: attaining superior performance
      through deliberate practice.
AB  - Exceptional performance is frequently attributed to genetic differences in
      talent. Since Sir Francis Galton's book, Hereditary Genius, many scientists have
      cited heritable factors that set limits of performance and only allow some
      individuals to attain exceptional levels. However, thus far these accounts have
      not explicated the causal processes involved in the activation and expression of
      unique genes in DNA that lead to the emergence of distinctive physiological
      attributes and cognitive capacities (innate talent). This article argues on the
      basis of our current knowledge that it is possible to account for the development
      of elite performance among healthy children without recourse to innate talent
      (genetic endowment)--excepting the innate determinants of body size. Our account
      is based on the expert-performance approach and proposes that the distinctive
      characteristics of exceptional performers are the result of adaptations to
      extended and intense practice activities that selectively activate dormant genes
      that are contained within all healthy individuals' DNA. Furthermore, the
      theoretical framework of expert performance explains the apparent emergence of
      early talent by identifying factors that influence starting ages for training and
      the accumulated engagement in sustained extended deliberate practice, such as
      motivation, parental support, and access to the best training environments and
      teachers. In sum, our empirical investigations and extensive reviews show that
      the development of expert performance will be primarily constrained by
      individuals' engagement in deliberate practice and the quality of the available
      training resources.

PMID- 19743556
TI  - Tibetan medicine: a complementary science of optimal health.
AB  - Traditional medical systems are challenging because their theories and practices
      strike many conventionally trained physicians and researchers as
      incomprehensible. Should modern medicine dismiss them as unscientific, view them
      as sources of alternatives hidden in a matrix of superstition, or regard them as
      complementary sciences of medicine? We make the latter argument using the example
      of Tibetan medicine. Tibetan medicine is based on analytic models and methods
      that are rationally defined, internally coherent, and make testable predictions,
      meeting current definitions of "science." A ninth century synthesis of Indian,
      Chinese, Himalayan, and Greco-Persian traditions, Tibetan medicine is the most
      comprehensive form of Eurasian healthcare and the world's first integrative
      medicine. Incorporating rigorous systems of meditative self-healing and ascetic
      self-care from India, it includes a world-class paradigm of mind/body and
      preventive medicine. Adapting the therapeutic philosophy and contemplative
      science of Indian Buddhism to the quality of secular life and death, it features
      the world's most effective systems of positive and palliative healthcare. Based
      on qualitative theories and intersubjective methods, it involves predictions and
      therapies shown to be more accurate and effective than those of modern medicine
      in fields from physiology and pharmacology to neuroscience, mind/body medicine,
      and positive health. The possibility of complementary sciences follows from the
      latest view of science as a set of tools--instruments of social activity based on
      learned agreement in aims and methods--rather than as a monolith of absolute
      truth. Implications of this pluralistic outlook for medical research and practice
      are discussed.

PMID- 19743557
TI  - Mastery of the mind East and West: excellence in being and doing and everyday
      happiness.
AB  - Western psychological research on positive psychology and Buddhism have recently
      converged in their emphasis on the development of positive states, like states of
      excellence and everyday happiness. Yet, these traditions differ in their
      approaches to positive states, with respect to a state-trait and doing-being
      distinction. Western scientific research on peak performance emphasizes
      discontinuous, time-limited peak performance states wherein individuals do things
      extraordinarily well in sports and in the arts. The Eastern spiritual traditions
      emphasize continuous excellence of being, in the form of traits or character
      strengths. In both traditions mental imagery is a key ingredient to excellence
      training. With respect to everyday happiness, Western psychological research has
      focused on the role of meaning systems in the transformation of flow states into
      vital engagement in everyday life, while Buddhism stresses the role of meditation
      training to gain mastery over all levels of mind that leads to everyday
      happiness. Rorschach and tachistoscopic research on advanced meditators suggests
      that advance meditators have gained unusual mastery over states of mind not yet
      documented in the Western psychological research on positive psychology.

PMID- 19743558
TI  - "Look for the moral and sex sides of the problem": investigating Jewishness,
      desire, and discipline at Macy's Department Store, New York City, 1913.

PMID- 19743559
TI  - Tibetan medical interpretation of myelin lipids and multiple sclerosis.
AB  - Tibetan medicine integrates diet, lifestyle, herbs, and accessory therapies to
      increase health and longevity. A comparison of the three humor theory of Tibetan
      medicine and the three thermodynamic phase properties of myelin lipids
      exemplifies how integrating medical systems can increase understanding of complex
      chronic disabling conditions. As a correlative study to microscopically better
      understand multiple sclerosis (MS) from the view of Tibetan medicine, the
      physical disruption of central nervous system myelin membranes in MS is
      interpreted from the theory of the three humors (vital energies) of Tibetan
      medicine: rLung (Wind), MKhris pa (Bile), and Bad gen (Phlegm). The three classes
      of myelin lipids--phospholipids, sphingolipids, and cholesterol--are interpreted
      as one of three humors based on Langmuir isotherm thermodynamic measurements. The
      nature of rLung is movement or change. Myelin sphingolipids have rLung properties
      based on thermodynamic observations of changes in phase organization. MKhris pa
      is fire, energetic. Phospholipids have MKhris pa properties based on
      thermodynamic observations of being energetic membrane lipids with fast molecular
      motions and fluid-like properties. The nature of Bad gen is substance and form;
      it dominates body structure. Cholesterol relates to Bad gen because it dominates
      membrane structure. We propose a theoretical relationship whereby demyelination
      in MS is viewed as a continuum of imbalance of the three humors as understood in
      Tibetan medicine. Myelin lipid data is presented to support this theoretical
      relationship. Clinically, MS is, in general, a rLung-MKhrispa disorder in women
      and a Bad gen-MKhrispa disorder in men, with rLung-MKhrispa excess in both
      genders during exacerbation, inflammation, and demyelination. Studying Tibetan
      medicine in its traditional context will create an integrative model for the
      treatment of MS and other chronic conditions.

PMID- 19743560
TI  - Re: How well do psychosocial interventions work in bipolar disorder?

PMID- 19743561
TI  - The NICE way of influencing health spending: a conversation with Sir Michael
      Rawlins. Interview by Nicholas Timmins.
AB  - Ten years ago the National Institute for Health and Clinical Excellence (NICE)
      was set up to recommend to the National Health Services in England and Wales
      which treatments and procedures it should and should not pay for and to publish
      treatment guidelines. As the United States moves to engage in more study of the
      comparative effectiveness--and possibly the cost-effectiveness--of treatments,
      Sir Michael Rawlins, chairman of NICE since its inception, reflects on the
      lessons. A possible surprise: on balance, NICE has added to costs.

PMID- 19743562
TI  - The energy body and its functions: immunosurveillance, longevity, and
      regeneration.
AB  - There are three interrelated levels of a macromolecular energy-information relay
      system in the human body, each generated by a specific type of semiconductant
      tissue and each with a specific function. The surface layer of the energy body,
      generated by fluid connective tissue and known as the ordinary channel system or
      meridian system in traditional Chinese medicine (TCM), functions in the service
      of immunosurveillance through detection of distress signals and transmitting
      energy-information regarding immunoresponse. The middle layer of the energy body,
      generated by semiconductant hard and spongy bone tissue, known as the
      extraordinary channel system in TCM, functions in the service of longevity and
      regeneration, as described in Bodhidharma's classic, Bone Marrow Washing. The
      bone marrow energy-information system has direct relevance to modern stem-cell
      research on the role of stem cells in regeneration of injured tissue. The deepest
      layer of the energy body generated by semiconductant nervous system tissue
      notably the vagus nerve and spinal column, functions in the service of awakening
      consciousness and in immortality. This system is described in the Tibetan Inner
      Fire meditations as well as in the Taoist shen breathing practices. There is very
      little scientific understanding of the central channel system.

PMID- 19743563
TI  - Barnum's brothel: P.T.'s "last great humbug".

PMID- 19743564
TI  - Tell me your dreams: psychoanalysis and popular culture in Buenos Aires, 1930
      1950.

PMID- 19743565
TI  - The politics of "Limpieza de Sangre:" Juan de Ovando and his circle in the reign
      of Philip II.

PMID- 19743566
TI  - "An immoral speculation": Indian forced labor on the haciendas of Venezuela's Sur
      del Lago Zuliano, 1880-1936.

PMID- 19743567
TI  - Rivaroxaban: new drug. After hip or knee replacement surgery: LMWH is safer.
AB  - (1) The standard anticoagulant therapy for prevention of thrombosis after hip or
      knee replacement surgery is subcutaneous injection of a low-molecular-weight
      heparin, such as enoxaparin; (2) Rivaroxaban is an oral factor-Xa inhibitor
      anticoagulant approved for use in these indications in the European Union; (3)
      Four double-blind controlled trials in more than 12 000 patients undergoing hip
      or knee replacement surgery failed to show that rivaroxaban was any more
      effective than enoxaparin on relevant clinical outcomes; there was no reduction
      in mortality, nor in the incidence of pulmonary embolism and symptomatic deep
      venous thrombosis; (4) In the selected populations enrolled in these trials, the
      bleeding risk was similar in the rivaroxaban and enoxaparin groups. However, it
      is possible that very underweight or overweight patients have an increased
      bleeding risk with rivaroxaban; (5) More information is needed on the
      nephrotoxicity of rivaroxaban, and a risk of mitochondrial toxicity cannot be
      ruled out. Post-marketing studies also need to focus on the consequences of wound
      seepage, which is more frequent with rivaroxaban. (6) Rivaroxaban is metabolized
      by the cytochrome P450 isoenzyme CYP 3A4 and binds to P-glycoprotein, hence a
      high risk of pharmacokinetic interactions; (7) Rivaroxaban has the advantage of
      being an oral treatment that does not require laboratory monitoring. However, it
      seems best to monitor renal function. It should also be noted that there is no
      effective antidote if severe bleeding occurs; (8) In practice, for frail elderly
      patients, who are often polymedicated, it seems more prudent to continue using
      low-molecular-weight heparin, a drug with which we have more experience.

PMID- 19743568
TI  - Micafungin: new drug. Severe candidiasis: a third echinocandin, with life
      threatening hepatotoxicity.

PMID- 19743569
TI  - Caspofungin: new indication. Same indications in children as in adults.
AB  - Caspofungin is no more effective than amphotericin B in children but its adverse
      effect profile is somewhat different. Caspofungin has not been compared with
      azole antifungals.

PMID- 19743570
TI  - Nepafenac: new drug. After cataract surgery: just another NSAID eye drop. No
      better than other NSAID eye drops, and less convenient to use.

PMID- 19743571
TI  - Panitumumab: new drug. Metastatic colorectal cancer: don't make things worse!

PMID- 19743572
TI  - Methylnaltrexone: new drug. Opiate-induced constipation: barely more effective
      than placebo.

PMID- 19743573
TI  - Teriparatide: new indication. During corticosteroid therapy: no fewer clinical
      fractures. Unnecessarily inconvenient.

PMID- 19743574
TI  - Ixabepilone: new drug. Similar to taxanes, but no better.

PMID- 19743575
TI  - Trabectedin: new drug. Soft-tissue sarcomas: too many adverse effects.

PMID- 19743576
TI  - Betaine anhydrous: new drug. Homocystinuria: continued evaluation needed.

PMID- 19743577
TI  - Adverse effects of papillomavirus vaccines: pharmacovigilance data in 2008.
AB  - (1) Various groups have released reviews of the adverse effects reported with
      papillomavirus vaccines in 2008. The reports mainly involved local adverse
      effects, syncope and a few allergic reactions; (2) The frequency of these adverse
      effects seems low and similar to that observed with standard, well-known
      vaccines. No unexpected serious adverse effects occurred in 2008.

PMID- 19743578
TI  - Sevelamer reduces the efficacy of many other drugs.
AB  - (1) Sevelamer, a phosphate-binding polymer, is used to treat hyperphosphataemia
      in patients with chronic renal failure. Pharmacokinetic studies and some clinical
      reports have shown that sevelamer binds many drugs, including furosemide,
      ciclosporin and tacrolimus, thus making them less effective; (2) It is best to
      take sevelamer some time before or after other drugs.

PMID- 19743579
TI  - A washout period needed before switching from a neuroleptic to an amphetamine.
AB  - (1) Abrupt replacement of risperidone with methylphenidate can lead to severe
      agitation in children; (2) Abruptly switching from one pharmacological class to
      another can lead to complications.

PMID- 19743580
TI  - Salmeterol and formoterol: asthma aggravation. Use should be restricted.

PMID- 19743581
TI  - Oseltamivir: cardiac and visual disorders: add-on toxicity.

PMID- 19743582
TI  - Methylphenidate: abuse and dependence. Abuse confirmed in France.

PMID- 19743583
TI  - What's my line?

PMID- 19743585
TI  - Would you be willing to float if you could choose when and where?

PMID- 19743584
TI  - Disabled nurses discover new career paths.

PMID- 19743586
TI  - Meningococcal pneumonia.

PMID- 19743587
TI  - Reversing a bullying culture.

PMID- 19743588
TI  - National patient safety goals: changing, but the same.

PMID- 19743589
TI  - A most wonderful life.

PMID- 19743590
TI  - Financial facts: what are we going to do now?

PMID- 19743591
TI  - What real nurses do.

PMID- 19743592
TI  - Going green--finding your voice.

PMID- 19743593
TI  - A case for volunteerism (a conversation with my gut).

PMID- 19743594
TI  - Mahalo & Moha mobile heart care....

PMID- 19743595
TI  - Mentors share their valuable experiences with dental residents.

PMID- 19743596
TI  - A family legacy of caring in Hilo.

PMID- 19743597
TI  - Dental ergonomics 101.

PMID- 19743598
TI  - Meth mout.
AB  - Methamphetamine (meth) is a drug traditionally sought by groups living on the
      fringes of society. But now, it has entered the mainstream. Over the last five
      years, meth has seen a surge in abuse, media coverage and attention from law
      enforcement officers. Meth mouth is characterized by rampant caries, typically on
      the smooth surfaces of dentition. This article gives a history of meth use and
      abuse. It describes the condition of meth mouth and its etiology. Treatment
      options and other dental considerations are discussed.

PMID- 19743599
TI  - War of words. What can I do when I discover a patient has posted defamatory
      comments online?

PMID- 19743600
TI  - Allowing staff to practice outside their licenses increases liability exposure.

PMID- 19743601
TI  - NHS must go the extra mile.

PMID- 19743602
TI  - Private healthcare sector shows resilience amid economic gloom.

PMID- 19743603
TI  - Why does nursing workload spike every ten years?

PMID- 19743604
TI  - Dignity in all we do.
AB  - The RCN's dignity campaign is encouraging nurses to give respectful and
      compassionate care at all times.

PMID- 19743605
TI  - Recipe for success.
AB  - Uptake of a diabetes self-management course was low in one east London borough,
      so the course was redesigned to offer people choice.

PMID- 19743606
TI  - Health care support staff must be regulated.

PMID- 19743607
TI  - Medicines management.

PMID- 19743608
TI  - An educational programme for end of life care in an acute setting.
AB  - End of life care should be incorporated in all stages of nurse training. This
      article describes the development of a multiprofessional education programme for
      staff to support them in meeting the recommended standards of end of life care in
      an acute hospital setting. The programme was designed to help practitioners work
      imaginatively with the care decisions they are required to make with patients and
      their loved ones.

PMID- 19743609
TI  - Developing and implementing an oral care policy and assessment tool.
AB  - Oral hygiene is an essential aspect of nursing care. Poor oral care results in
      patients experiencing pain and discomfort, puts individuals at risk of
      nutritional deficiency and infection, and has an adverse effect on quality of
      life. This article describes how an oral care policy and assessment tool were
      updated to ensure the implementation of evidence-based practice at one hospital
      in the Republic of Ireland.

PMID- 19743610
TI  - Strategies to improve patients' adherence to medication.
AB  - This article explores issues surrounding adherence to medication. Terminology
      associated with the use of medication, most notably the terms compliance,
      concordance and adherence, are discussed. The article also explores factors that
      can influence the use of medication and discusses the role of nurses in
      supporting adherence to treatment.

PMID- 19743611
TI  - External fixation.

PMID- 19743612
TI  - Seeing the person.

PMID- 19743613
TI  - Health visiting: a critical service.

PMID- 19743614
TI  - Delivering value for money.

PMID- 19743615
TI  - The contemporary relevance of the mouse foot pad model for cultivating M. leprae.

PMID- 19743616
TI  - Collaborative programmes of research in leprosy: the INFIR programme.

PMID- 19743617
TI  - PCR-restriction fragment length polymorphism analysis as a tool for Mycobacterium
      species identification in lepromas for lepromin production.
AB  - OBJECTIVES: The aim of the present work was to standardise a PCR-Restriction
      Fragment Length Polymorphism analysis (PRA) as a tool to detect the
      mycobacteriologic composition of lepromas from leprosy patients used in the
      production of lepromin to improve the quality of the Mitsuda test. DESIGN: PCR
      Restriction Fragment Length Polymorphism analysis using hsp65 and rpoB genes were
      applied to 11 reference strains of mycobacteria, including M. leprae, and the
      obtained PRA profiles were compared to mycobacteria in clinical specimens.
      RESULTS: Out of the biopsies studied, 522% had DNA fragment amplified for both
      genes (hsp65 and rpoB) for M. leprae. However, other Mycobacterium species were
      observed in samples of lepromatous leprosy patients. Here we discussed the
      importance of mycobacteria identification in the antigen of Mitsuda production to
      be used in the evaluation of leprosy. CONCLUSIONS: Our results suggest that the
      use of the molecular approach for sample selection can contribute to an
      improvement in the quality of produced lepromin.

PMID- 19743618
TI  - Comparative study of uniform-MDT and WHO MDT in Pauci and Multi bacillary leprosy
      patients over 24 months of observation.
AB  - STUDY DESIGN: An open comparative study between WHO MDT and U-MDT regimen in all
      types of leprosy over 24 months of observation was carried out at Gandhi
      Hospital, Secunderabad, India. Periodic assessment of clinical and
      histopathological parameters at 6 monthly intervals was performed in both groups
      of patients for grading response to the treatment regimens. PATIENTS AND METHODS:
      One hundred and twenty-seven newly diagnosed, untreated leprosy patients
      classified into PB (< or = 5 skin lesions) and MB leprosy (> 5 skin lesions) were
      alternately allocated into Study (U-MDT for 6 months) and Control groups (WHO
      MDT) at entry. Out of the 127 patients included, 64 patients (M-44, F-20; PB
      leprosy 32 & MB leprosy 32) could be followed-up regularly. These 64 patients
      were clinically assessed and graded into Good, Moderate and Poor response at 6,
      12 and 18 months of the study, and 44 of these patients were also assessed at 24
      months of the study. Histopathological assessments were also done at the above
      intervals. RESULTS: PB PATIENTS: The control and study groups comprised of 14 and
      18 patients respectively. When clinical grades were compared, the numbers of
      Moderate and Good responses were 78% and 61% at 6 months, 86% and 94% at 18
      months and 82% and 100% at 24 months in the PB Control and Study groups
      respectively, suggesting better progressive improvement in the Study group
      compared to Control group, but the differences were not significant (At 6 months
      P = 02195, at 18 months 0.7305, at 24 months P = 0.3500) Histopathological
      assessment at 12 months, showed higher percentage of Good responses (100%) in the
      PB-Study group than in the PB-Control group (86%). MB PATIENTS: The MB Control
      and Study groups comprised of 22 and 10 patients respectively. In clinical
      improvement grades, Good responses in the Control group was 36%, 45% and 77% at
      12, 18 and 24 months of study, whereas the Study group did not have a single Good
      response at 12 and 18 months with the Poor responses being 50%, 67% and 75% at
      12, 18 and 24 months. These differences between the groups were significant at
      all periods of assessment. (At 12 months P = 0.0465, at 18 months P = 0.0014, at
      24 months P = 0.0064). Histopathological assessment showed higher the percentage
      of Good responses in Control group (100%) compared to Study group (50%) at 18
      months. CONCLUSION: U-MDT of 6 months duration was well tolerated and effective
      in patients with PB leprosy but was too short a regimen adequately to treat
      patients with MB leprosy.

PMID- 19743619
TI  - Dental and oral condition in leprosy patients from Serra, Brazil.
AB  - OBJECTIVES: To describe dental and periodontal diseases and oral lesions in newly
      diagnosed leprosy patients. DESIGN: Cohort study with 99 leprosy patients carried
      out at the Leprosy Control Programme Outpatient Clinic, Serra-ES, Brazil. A
      questionnaire about demographic and clinical data was used. Clinical oral
      examination was performed through the decayed, missing and filled teeth index
      (DMFT index), the use and need of prosthesis, periodontal disease and the
      presence of mucous membrane oral lesions. Skin and oral mucous biopsies were also
      undertaken. RESULTS: Decayed teeth were present in 73% of the patients, at least
      one lost tooth was present in 71.4%, the mean of the number of lost teeth among
      the patients in this survey was 88; and 603% of the patients did not have their
      teeth filled. Periodontal disease was present in 80.8%, and gingival bleeding in
      92% of the patients. DMFT index average was 14.4. Nine out of the 63 patients
      presented with oral clinical lesions, however, most of them presented with
      unspecific chronic inflammation and typical epithelial hyperplasia. CONCLUSIONS:
      These newly diagnosed leprosy patients were similar in respect of oral health to
      the normal Brazilian population. Serious dental loss and edentulism were
      observed, as were a high DMFT index and frequency of periodontal diseases. These
      data highlight a lack of oral health prevention and treatment and poor access
      even when available.

PMID- 19743620
TI  - Occurrence and management of leprosy reaction in China in 2005.
AB  - BACKGROUND: Leprosy reactions are a major cause of disability before, during and
      after anti-bacterial treatment. Prompt diagnosis and correct management of
      reaction is a crucial matter for improving the quality of leprosy health
      services. OBJECTIVES: To describe the pattern of leprosy reaction and its
      management in China during 2005. METHODS: A retrospective survey using a
      questionnaire was carried out in all the provinces of China at the beginning of
      2006. Patients included were those presenting with leprosy reaction between 1
      January and 31 December 2005. RESULTS: 452 questionnaires from 25 provinces were
      analysed. There were 313 male and 139 female patients who had 159 Type I
      reactions, 273 Type II reactions and 20 Type I and II mixed reaction. 72.4% of
      reactions occurred in the first year of MDT and 27.6% of patients during the
      second year of MDT. The highest frequency of reaction was during the first 6
      months of MDT; 57.3% of patients developed new nerve impairment during and after
      MDT. CONCLUSIONS: New nerve function impairment and disability still occurs among
      patients during and after MDT. The early detection and management of leprosy
      reaction remains important.

PMID- 19743621
TI  - Twenty five years follow up of MB leprosy patients retreated with a modified MDT
      regimen after a full course of dapsone mono-therapy.
AB  - BACKGROUND: The relentless emergence of dapsone resistance amongst M. leprae
      threatened leprosy control programmes, and increased the relapse rate of patients
      cured with dapsone monotherapy. OBJECTIVE: The study aimed to analyse the effect
      on the relapse rate of dapsone-cured multibacillary (MB) leprosy patients, of re
      treatment, using a multidrug therapy (MDT) regimen which differed from the WHO
      recommended regimen. DESIGN: 794 MB leprosy patients who had been released from
      treatment after dapsone monotherapy were selected, amongst them 657 were re
      treated for 1 year using the modified multidrug therapy regimen (mMDT) including
      rifampicin, clofazimine and dapsone, and 137 patients were observed as control
      cases. RESULTS: The regimen was well tolerated with good compliance: 620 patients
      completed re-treatment with mild side effects and a low incidence of leprosy
      reactions. There was a statistically significant difference between the relapse
      rates of re-treated and control groups (chi squaredf = 57.44, P < 0.001).
      Furthermore, the relapses in the re-treated group were significantly more likely
      to be later than those in the control group (t = 25.62, P < 0.001). CONCLUSIONS:
      Re-treatment with this modified regimen is acceptable and can reduce the risk of
      early relapse in dapsone-cured patients. The problem of persisters causing late
      relapse is likely to remain.

PMID- 19743622
TI  - Intra and post operative complications and visual outcomes following cataract
      surgery in leprosy patients.
AB  - OBJECTIVES: The occurrence of intra and post operative complications was compared
      in different groups of leprosy patients. The association between post operative
      and intra operative complications was studied, and how visual outcomes were
      affected by these complications. We also share our medical management and
      surgical techniques that might help minimise intra operative complications and
      improve visual outcomes. DESIGN: A retrospective analysis of 1024 cataract
      operations in 786 leprosy patients over an 11 year period from 1995 to 2006 at
      Kothara Community Hospital, a rural hospital belonging to The Leprosy Mission
      Trust India, located in the Amravati district of Maharashtra. RESULTS: 3.5% of
      eyes had intra operative complications and 22% of eyes had post operative
      complications, with no appreciable difference in incidence of intra operative
      complications in the various groups of patients studied. Post operative uveitis
      was higher in the MB (3.2%), smear positive (6.5%), UT (6%), eyes with leprosy
      related ocular disease (6.4%) and lepra reaction (12%) groups. Overall, eyes with
      leprosy related complications and eyes operated on during lepra reactions had
      more post operative complications compared to the group without. Visual outcomes
      for eyes with intra and post operative complications were poorer than the groups
      without. CONCLUSIONS: Cataract surgery in the hands of a careful and well trained
      surgeon, who is familiar with ocular leprosy and can modify the surgical
      technique as necessary, is safe and associated with minimal intra operative and
      post operative complications.

PMID- 19743623
TI  - Self care groups and ulcer prevention in Okegbala, Nigeria.
AB  - OBJECTIVE: To assess the impact of the three self-care Groups on ulcer prevalence
      and readmission rates in Okegbala hospital. DESIGN: A retrospective, descriptive
      study. The evaluation combined four data collection methods namely (i) records
      survey, (ii) semi-structured interviews of individual members of self-care
      groups, (iii) group discussions and (iv) key informant interviews. RESULTS:
      Record surveys show that the ulcer prevalence has decreased by almost 75% since
      the adoption of the self-care group; admissions to hospital for ulcer care have
      reduced, and the mean interval between admissions has increased by 7 months. Semi
      structured interviews and group discussions show that all members have a greater
      sense of control of their ulcers and general health; and that self-care groups
      have a potential of catalysing community solidarity and development. CONCLUSIONS:
      This small study shows that self-care groups are valuable for reducing ulcers and
      giving members a greater sense of control of their ulcers and general health
      resulting in fewer hospital admissions. We recommend a multi-centre, controlled,
      prospective study incorporating different settings (e.g. urban, rural, near
      hospitals, within field leprosy programmes) to test these findings. Such a study
      has the potential of influencing policy and health-service reorientation of ulcer
      care in future.

PMID- 19743624
TI  - Test-retest reliability of the Screening Activity Limitation and Safety Awareness
      (SALSA) scale in North-West Nigeria.
AB  - INTRODUCTION: The present study examines the inter-tester and intra-tester
      reliability of the recently developed scale for Screening of Activity Limitation
      and Safety Awareness (SALSA) in North-West Nigeria. The scale was developed
      through collaborative research in five countries around the world. METHODOLOGY:
      One hundred and three people affected by leprosy from three states in North-West
      Nigeria participated in the study. A Hausa translation of the 20-item SALSA
      questionnaire was used by four trained health staff to interview the
      participants. Seventy-five paired interviews were conducted where the second
      interview was administered by a different interviewer from the first at intervals
      of 4-76 days (median 52). Twenty-eight paired interviews were conducted, both by
      the same interviewer, at intervals of 52-71 days (median 63). RESULTS: Inter
      tester reliability: All 20 items had Kappa's ranging from 0.45-0.8; 15 items had
      Kappa's > 0.6; 8 items had Kappa's > 0.7. Intra-tester reliability: All 20 items
      had Kappa's ranging from 0.51-1; 15 items had Kappa's > 0.6; 12 items had Kappa's
      > 0.7. For inter-tester reliability, the first interview had a mean SALSA score
      of 36.5 (95% CI = 34.96-38.05). The second interview had a mean of 35.02 (95% CI
      = 35.01-37.99). For intra-tester reliability, the mean SALSA scores of first and
      second interviews were 27.36 (95% CI = 24.36-30.36) and 26.68 (95% CI = 23.93
      29.43), respectively. CONCLUSIONS: The Hausa translation of SALSA has an
      acceptable reliability in Nigeria provided the interviewers are well trained.

PMID- 19743625
TI  - Rapid killing of M. leprae by moxifloxacin in two patients with lepromatous
      leprosy.
AB  - INTRODUCTION: Previously we reported a 2-month clinical trial of moxifloxacin
      therapy in eight patients with MB leprosy (7 LL and 1 BL), finding both rapid
      killing of M. leprae and clinical improvement, without serious side effects or
      toxicities. Here we report the outcomes in two patients treated with
      moxifloxacin. DESIGN: Two previously untreated LL patients were treated with a
      single 400 mg dose of moxifloxacin, no therapy for 7 days and then daily 400 mg
      moxifloxacin for 48 days. Clinical response, viability of M. leprae in the skin,
      and side effects/toxicities were carefully monitored. RESULTS: In both patients a
      single dose of moxifloxacin resulted in significant killing of M. leprae (P <
      0.001%). In both patients no viable M. leprae were found after 15 doses of
      moxifloxacin. Improvement in skin lesions occurred again remarkably rapidly and
      no untoward effects were noted. CONCLUSION: Loss of viable M. leprae was quite
      rapid, similar to that found previously only for rifampicin, patients improved
      rapidly, and moxifloxacin was well tolerated.

PMID- 19743626
TI  - A case of lepromatous leprosy with multiple relapses.
AB  - We report a case of multiple relapses in a lepromatous leprosy patient after
      treatment with World Health Organisation (WHO) recommended multibacillary
      multidrug therapy (MBMDT). The patient responded well to reintroduction of MDT
      after each relapse.

PMID- 19743627
TI  - Post-traumatic inoculation tuberculoid leprosy after injury with a glass bangle.
AB  - A lesion of tuberculoid leprosy in an Indian lady presenting at the site of
      injury from a broken glass bangle is reported. The diagnosis was by classical
      clinical features and histopathology. The importance of the skin in leprosy
      transmission is emphasised.

PMID- 19743628
TI  - The functional outcome of posterior tibial tendon transfer for foot drop in
      leprosy. The results of one to 5 years follow up.

PMID- 19743629
TI  - Quality service to leprosy patients using mobile phones and pagers.

PMID- 19743630
TI  - A unique museum in Mumbai--Acworth Leprosy Museum.

PMID- 19743631
TI  - Assessment of common hyperelastic constitutive equations for describing normal
      and osteoarthritic articular cartilage.
AB  - With the aim of providing information for modelling joint and limb systems,
      widely available constitutive hyperelastic laws are evaluated in this paper for
      their ability to predict the mechanical responses of normal and osteoarthritic
      articular cartilage. Load-displacement data from mechanical indentation were
      obtained for normal and osteoarthritic cartilage at 0.1 s(-1) and 0.025 s(-1) and
      converted to the stress-stretch ratio. The data were then fitted to the Arruda
      Boyce, Mooney-Rivlin, neo-Hookean, Ogden, polynomial, and Yeoh hyperelastic laws
      in the MATLAB environment. Although each of the hyperelastic laws performed
      satisfactorily at the higher rate of loading, their ability to fit experimental
      data at the lower loading rate varied considerably. For the preferred models,
      coefficients were provided for stiff, soft, and average tissues to represent
      normal and degraded tissue at high and low loading rates. The present authors
      recommend the use of the Mooney-Rivlin or the Yeoh models for describing both
      normal and degraded articular cartilage, with the Mooney-Rivlin model providing
      the best compromise between accuracy and required computational power.

PMID- 19743632
TI  - Non-linear analysis of body responses to functional electrical stimulation on
      hemiplegic subjects.
AB  - Functional electrical stimulation (FES) is a method of applying low-level
      electrical currents to restore or improve body functions lost through nervous
      system impairment. FES is applied to peripheral nerves that control specific
      muscles or muscle groups. Application of advanced signal computing techniques to
      the medical field has helped to achieve practical solutions to the health care
      problems accurately. The physiological signals are essentially non-stationary and
      may contain indicators of current disease, or even warnings about impending
      diseases. These indicators may be present at all times or may occur at random on
      the timescale. However, to study and pinpoint these subtle changes in the
      voluminous data collected over several hours is tedious. These signals, e.g.
      walking-related accelerometer signals, are not simply linear and involve non
      linear contributions. Hence, non-linear signal-processing methods may be useful
      to extract the hidden complexities of the signal and to aid physicians in their
      diagnosis. In this work, a young female subject with major neuromuscular
      dysfunction of the left lower limb, which resulted in an asymmetric hemiplegic
      gait, participated in a series of FES-assisted walking experiments. Two three
      axis accelerometers were attached to her left and right ankles and their
      corresponding signals were recorded during FES-assisted walking. The
      accelerometer signals were studied in three directions using the Hurst exponent
      H, the fractal dimension (FD), the phase space plot, and recurrence plots (RPs).
      The results showed that the H and FD values increase with increasing FES,
      indicating more synchronized variability due to FES for the left leg (paralysed
      leg). However, the variation in the normal right leg is more chaotic on FES.

PMID- 19743633
TI  - Feedback control of the neuromusculoskeletal system in a forward dynamics
      simulation of stair locomotion.
AB  - The aim of this study is to employ feedback control loops to provide a stable
      forward dynamics simulation of human movement under repeated position constraint
      conditions in the environment, particularly during stair climbing. A ten-degrees
      of-freedom skeletal model containing 18 Hill-type musculotendon actuators per leg
      was employed to simulate the model in the sagittal plane. The postural tracking
      and obstacle avoidance were provided by the proportional-integral-derivative
      controller according to the modulation of the time rate change of the joint
      kinematics. The stability of the model was maintained by controlling the velocity
      of the body's centre of mass according to the desired centre of pressure during
      locomotion. The parameters of the proposed controller were determined by
      employing the iterative feedback tuning approach to minimize tracking errors
      during forward dynamics simulation. Simultaneously, an inverse-dynamics-based
      optimization was employed to compute a set of desired musculotendon forces in the
      closed-loop simulation to resolve muscle redundancy. Quantitative comparisons of
      the simulation results with the experimental measurements and the reference
      muscles' activities illustrate the accuracy and efficiency of the proposed method
      during the stable ascending simulation.

PMID- 19743634
TI  - Biotribological investigation of a multi-tube foot for traction generation in a
      medical microrobot.
AB  - In recent years, efforts to develop microrobots for medical applications have
      been expanding. One of the key design issues in such microrobots is to attain
      adequate frictional interaction between the robotic foot and the organ tissue. In
      particular, it is important to generate the necessary frictional force without
      damaging the tissue. In this work, a design for the robotic foot was proposed on
      the basis of the frictional behaviour of a tube structure. Fundamental
      experiments were initially performed to understand the biotribological behaviour
      of the tube and rod structures. The design was then modified to a multi-tube
      structure to achieve adequate frictional behaviour. Biotribological investigation
      of a multi-tube foot in contact with a small intestine specimen of a pig was
      conducted using a pin-on-reciprocator type biotribotester. It was found that
      there is an optimum number and arrangement of the tubes for generating high
      frictional force. Experimental results showed that a nine-tube foot had the
      highest initial friction coefficient of about 1.5. The major frictional mechanism
      was determined to be interlocking between the tubes and the surface structures of
      the intestine specimen. The results of this work will aid the optimum design of
      frictional surface for medical microrobots and other biological devices.

PMID- 19743635
TI  - Design and implementation of robust controllers for a gait trainer.
AB  - This paper applies robust algorithms to control an active gait trainer for
      children with walking disabilities. Compared with traditional rehabilitation
      procedures, in which two or three trainers are required to assist the patient, a
      motor-driven mechanism was constructed to improve the efficiency of the
      procedures. First, a six-bar mechanism was designed and constructed to mimic the
      trajectory of children's ankles in walking. Second, system identification
      techniques were applied to obtain system transfer functions at different
      operating points by experiments. Third, robust control algorithms were used to
      design Hinfinity robust controllers for the system. Finally, the designed
      controllers were implemented to verify experimentally the system performance.
      From the results, the proposed robust control strategies are shown to be
      effective.

PMID- 19743636
TI  - Design and simulation of a poly(vinyl alcohol)-bacterial cellulose nanocomposite
      mechanical aortic heart valve prosthesis.
AB  - In this study, a polymeric aortic heart valve made of poly(vinyl alcohol) (PVA)
      bacterial cellulose (BC) nanocomposite is simulated and designed using a
      hyperelastic non-linear anisotropic material model. A novel nanocomposite
      biomaterial combination of 15 wt % PVA and 0.5 wt % BC is developed in this
      study. The mechanical properties of the synthesized PVA-BC are similar to those
      of the porcine heart valve in both the principal directions. To design the
      geometry of the leaflets an advance surfacing technique is employed. A Galerkin
      based non-linear finite element method is applied to analyse the mechanical
      behaviour of the leaflet in the closing and opening phases under physiological
      conditions. The model used in this study can be implemented in mechanical models
      for any soft tissues such as articular cartilage, tendon, and ligament.

PMID- 19743637
TI  - Predicting spontaneous termination of atrial fibrillation based on the RR
      interval.
AB  - It is important to characterize conditions under which atrial fibrillation (AF)
      is likely to terminate spontaneously. A novel method is proposed here. Eleven
      features are first extracted to characterize RR interval and Poincare plot from a
      statistical viewpoint and a geometric viewpoint respectively. Then sequential
      forward search (SFS) algorithm is utilized for feature selection. Finally, a
      fuzzy support vector machine (FSVM) with a new fuzzy membership is applied for AF
      termination prediction. The method is studied with an AF database of
      electrocardiogram (ECG) recordings provided by PhysioNet for the Cardiology
      Challenge 2004. It is divided into a training set and two testing sets (A and B).
      Experiment results show that 100 per cent of testing set A and 100 per cent of
      testing set B are correctly classified, together with 92.3 per cent of non
      terminating and soon-terminating AF correctly classified. It demonstrates that
      the proposed method can predict spontaneous termination of AF effectively.

PMID- 19743638
TI  - High-solid-content hydroxyapatite slurry for the production of bone substitute
      scaffolds.
AB  - Key to various bone substitute scaffold production techniques is the development
      of free-flowing ceramic slurry with optimum theological properties. The aim is to
      achieve a colloidal suspension with as high a solid content as possible while
      maintaining a low viscosity which easily penetrates the pores of relevant
      sacrificial templates. The following investigation describes the optimization of
      a hydroxyapatite slip and demonstrates its potential application in scaffold
      production. Using predominantly spherical particles of hydroxyapatite of between
      0.82 microm and 16.2 microm, coupled with a 2 wt % addition of the anionic
      polyelectrolyte, ammonium polyacrylate, an 80 wt % (55.9 vol%) hydroxyapatite
      solid loaded slip with a viscosity of approximately 126mPas has been developed.
      Its ability to infiltrate and replicate porous preforms has been shown using
      polyurethane foam. The enhanced particle packing achieved has allowed for the
      production of scaffolds with highly dense and uniform grain structures. The
      results represent a significant improvement in current slurry production
      techniques and can be utilized to develop high-density ceramic bone substitute
      scaffolds.

PMID- 19743639
TI  - Stress analysis in the mandibular condyle during prolonged clenching: a
      theoretical approach with the finite element method.
AB  - Parafunctional habits, such as bruxism and prolonged clenching, have been
      associated with functional overloading in the temporomandibular joint (TMJ),
      which may result in internal derangement and osteoarthrosis of the TMJ. In this
      study, the distributions of stress on the mandibular condylar surface during
      prolonged clenching were examined with TMJ mathematical models. Finite element
      models were developed on the basis of magnetic resonance images from two subjects
      with or without anterior disc displacement of the TMJ. Masticatory muscle forces
      were used as a loading condition for stress analysis during a 10 min clenching.
      In the asymptomatic model, the stress values in the anterior area (0.100 MPa) and
      lateral area (0.074 MPa) were relatively high among the five areas at 10 min. In
      the middle and posterior areas, stress relaxation occurred during the first 2
      min. In contrast, the stress value in the lateral area was markedly lower (0.020
      MPa) than in other areas in the symptomatic model at 10 min. The largest stress
      (0.050 MPa) was located in the posterior area. All except the anterior area
      revealed an increase in stress during the first 2 min. The present result
      indicates that the displacement of the disc could affect the stress distribution
      on the condylar articular surface during prolonged clenching, especially in the
      posterior area, probably leading to the cartilage breakdown on the condylar
      articular surface.

PMID- 19743640
TI  - Controlling force variations during soft-tissue grasping.
AB  - This paper develops a mechatronic grasper that can be used to investigate a
      preliminary experiment of a simple model-independent approach to control soft
      tissue grasping based on, first, measurement of the total tangential grasp force
      and, second, discrimination of relaxation and frictional forces by imposing a
      limited basis set of grasper motions. The main motivation for this work is that
      tissue grasping is an important component of surgical procedures. However, there
      is a major criterion which should be achieved: maintaining grasp stability while
      avoiding damage due to excessive grip force. Thus, the automation of grasping
      force control requires a controller to apply grasping forces just sufficient to
      maintain grasp stability. This task is complicated by the serially connected
      dynamics of grasp friction and tissue relaxation.

PMID- 19743641
TI  - Design and evaluation of a novel triaxial isometric trunk muscle strength
      measurement system.
AB  - Maximal strength measurements of the trunk have been used to evaluate the maximum
      functional capacity of muscles and the potential mechanical overload or overuse
      of the lumbar spine tissues in order to estimate the risk of developing
      musculoskeletal injuries. A new triaxial isometric trunk strength measurement
      system was designed and developed in the present study, and its reliability and
      performance was investigated. The system consisted of three main revolute joints,
      equipped with torque sensors, which intersect at L5-S1 and adjustment facilities
      to fit the body anthropometry and to accommodate both symmetric and asymmetric
      postures in both seated and standing positions. The dynamics of the system was
      formulated to resolve validly the moment generated by trunk muscles in the three
      anatomic planes. The optimal gain and offset of the system were obtained using
      deadweights based on the least-squares linear regression analysis. The R2 results
      of calibration for all loading courses of all joints were higher than 0.99, which
      indicated an excellent linear correlation. The results of the validation analysis
      of the regression model suggested that the mean absolute error and the r.m.s.
      error were less than 2 per cent of the applied load. The maximum value of the
      minimum detectable change was found to be 1.63 Nm for the sagittal plane torque
      measurement, 0.8 per cent of the full-scale load. The trial-to-trial variability
      analysis of the device using deadweights provided intra-class correlation
      coefficients of higher than 0.99, suggesting excellent reliability. The cross
      talk analysis of the device indicated maximum cross-talks of 1.7 per cent and 3.4
      per cent when the system was subjected to flexion-extension and lateral bending
      torques respectively. The trial-to-trial variability of the system during in-vivo
      strength measurement tests resulted in good to excellent reliability, with intra
      class correlation coefficients ranging from 0.69 to 0.91. The results of the
      maximum voluntary isometric torques exertion measurements for 30 subjects
      indicated good agreement with the previously published data in the literature.
      The extensive capabilities and high reliability of the system are promising for
      more comprehensive investigations on the trunk biomechanics in future, e.g.
      isometric strength measurement at symmetric and asymmetric postures, muscle
      endurance, and recruitment pattern analysis.

PMID- 19743642
TI  - A biomechanical investigation of the anteromedial and posterolateral bands of the
      porcine anterior cruciate ligament.
AB  - The bipartite nature of the porcine anterior cruciate ligament has been
      documented, but its biomechanics have not been investigated. The need for such
      knowledge has recently been heightened with xenografting advances such as the
      introduction of the porcine patellar tendon as a human anterior cruciate ligament
      graft. The aim of this study is to compare the biomechanical properties of the
      intact anterior cruciate ligament with that of its two bands. 15 intact porcine
      anterior cruciate ligament-bone, 15 anteromedial band-bone, and 15 posterolateral
      band-bone complexes were prepared for tensile testing at 0.33 mm/s. Structural
      (load, deformation, stiffness, and energy absorbed) and material (stress, strain,
      modulus, and strain energy density) properties were analysed. Analysis of
      variance identified significantly higher ultimate load, stiffness, and energy
      absorbance in the intact porcine ligament when compared with its anteromedial
      band (p = 0.028). However, the intact ligament was only significantly higher in
      ultimate load when compared to its posterolateral band (p = 0.031). All ligament
      bone complexes failed at similar deformations and strains, suggesting a strain
      dependent failure mechanism. The intact porcine anterior cruciate ligament
      exhibited higher ultimate load, stiffness, and energy absorption than its two
      bands in isolation. The posterolateral band of the porcine anterior cruciate
      ligament constitutes a large proportion of the overall restraining function of
      the entire anterior cruciate ligament.

PMID- 19743643
TI  - Microchip system for monitoring microbial physiological behaviour under drug
      influences.
AB  - Single-step real-time high-throughput monitoring of drug influences on bacterial
      cell behaviour has become important with growing interests in personalized
      therapy and medication. Conventional microchip assemblies to perform similar work
      do exist. However, most of these devices have complex set-ups incorporating
      micromixers, separators, pumps, or valves. These microcomponents can sometimes
      damage the entities being monitored because of the creation of unfavourable
      biological environments. This paper presents a microchip-based system that
      enables single-step mixing of two solutions in various ratios, without the need
      for additional microcomponents such as mixers and pumps, in order to screen
      effectively their combinatory effects on cell outcomes. In this work, in-vitro
      experiments were carried out using ampicillin at various concentrations to
      investigate their effects on Escherichia coli (E. coli). Results showed that the
      microchip provided effective screening, which yielded useful results such as
      effective dosages, ineffective dosages, and other possible outcomes; for
      instance, in this case, the occurrence of adaptive mutation of the bacteria at
      certain drug concentrations. Comparative microbiological laboratory tests were
      carried out as standard for confirmation of the results.

PMID- 19743644
TI  - Development of a customized density-modulus relationship for use in subject
      specific finite element models of the ulna.
AB  - Assigning an appropriate density-modulus relationship is an important factor when
      applying inhomogeneous material properties to finite element models of bone. The
      purpose of this study was to develop a customized density-modulus equation for
      the distal ulna, using beam theory combined with experimental results. Five
      custom equations of the form E= ap(b) were used to apply material properties to
      models of eight ulnae. All equations passed through a point (1.85, Ec), where p =
      1.85 g/cm3 represents the average density of cortical bone. For custom equations
      (1) to (3), Ec was predicted using beam theory, and the value of b was varied
      within the range reported in the literature. Custom equations (4) and (5) used
      other values of Ec from the literature, while keeping b constant. Results
      obtained from the custom equations were compared with those from other equations
      in the literature, and with experimental results. The beam theory analysis
      predicted Ec = 21 +/- 1.6 GPa, and the three custom equations using this value
      tended to have the lowest errors. The power of the equations did not affect the
      results as much as the value used for Ec. Overall, a customized density-modulus
      relationship for the ulna was generated, which provided improved results over
      using previously reported density-modulus equations.

PMID- 19743645
TI  - Preventable readmissions: a prime target for reform.

PMID- 19743646
TI  - Assessing IT expenditures in an uncertain economy.
AB  - Approaches that CFOs and CIOs may consider when determining how to gain the most
      value from IT investments at the least cost include: Portfolio review. Contract
      review and negotiation. Contract negotiation. Analyses of IT spend, return, labor
      productivity, and strategic projects. Lifecycle management. Data management.
      Taking advantage of crisis.

PMID- 19743647
TI  - MMSEA section 111: do you know if it applies to your organization?
AB  - Section 111 of the Medicare, Medicaid, and SCHIP Extension Act of 2007 requires
      certain self-insured hospitals to report to CMS when the hospital makes a payment
      for a claim brought by a Medicare beneficiary and/or has ongoing responsibility
      for a Medicare beneficiary's medical costs. To comply with this requirement,
      responsible reporting entities (RREs) must register with CMS by Sept.30, 2009,
      and submit claim files for testing during the period from Jan. 1 through March
      31, 2010. RREs must comply with the requirement beginning with second quarter of
      2010.

PMID- 19743648
TI  - Jay Crowley the FDA's perspective on the unique device identification system.

PMID- 19743649
TI  - Jane Pleasants a provider's perspective on the unique device identification
      system.

PMID- 19743650
TI  - Responsibility-based A/R reporting: how one health system drove performance with
      analytics.
AB  - An automated accounts receivable (A/R) reporting package should provide managers
      with data-driven information to help them respond to emerging trends in the
      revenue cycle. Responsibility for clearly defined account portfolios should be
      assigned to managers, and targets should be established. This data-driven
      approach with its culture of responsibility can help healthcare organizations
      reach their A/R goals.

PMID- 19743651
TI  - No more lost clinic charges: using IT for recovery and measurement.
AB  - Identifying missed opportunities for revenue requires examining front-end
      processes and how they might join with transactions generated during processes of
      care. Linking the initiation of a charge to an important process in the clinic
      procedures helps ensure capture of both professional and facility charges.
      Implementing a software program to automatically initiate correlated charges and
      measuring the change in charges and revenue are steps that provide a substantial
      revenue opportunity for healthcare organizations.

PMID- 19743652
TI  - Transforming revenue cycle processes in an indigent care setting.
AB  - Steps that Grady Health System in Atlanta undertook in transforming its revenue
      cycle include: Conducting a complete revenue cycle assessment. Enhancing staff
      skill levels and customer service techniques--and holding staff. accountable for
      errors. Automating processes that previously were performed manually. Validating
      applications for financial assistance electronically. Screening for
      Medicare/Medicaid eligibility among self-pays.

PMID- 19743653
TI  - Executing the double win: protect your cash flow during a patient accounting
      system install.
AB  - MultiCare Health System's plan for ensuring that its patient accounting system
      implementation would bring rapid financial benefits comprised eight basic steps:
      Set baselines and establish goals. Identify key leadership stakeholders across
      departmental lines. Identify team resources. Establish roles and
      responsibilities. Identify and prepare for potential risks. Develop guiding
      principles. Develop key reporting and monitoring tools. Conduct daily monitoring.

PMID- 19743654
TI  - 6 questions to ask when 'hunting' for reimbursement.
AB  - There are six questions negotiators for medical group practices should ask in
      trying to secure the right level of payer reimbursement: Which CPT codes
      characterize the practice? What codes are most valuable to the practice? What
      fees are acceptable to the practice? Which payers are paying acceptable fees? How
      can payer schedules be made more acceptable? What is the financial return from
      fee negotiations?

PMID- 19743655
TI  - Measuring collections effort improves cash performance.
AB  - Having a satisfied work force can lead to an improved collections effort. Hiring
      the right people and training them ensures employee engagement. Measuring
      collections effort and offering incentives is key to revenue cycle success.

PMID- 19743656
TI  - EHR triggers: a force for improved care--and revenue.
AB  - Certain process-of-care measures advocated by CMS on its Hospital Compare web
      site can provide a basis for identifying patients who should be screened for
      certain medical conditions for which they are at high risk. Automatic triggers
      built into an EHR can help physicians identify such patients and establish
      medical necessity for services that both improve patient care and increase
      revenue for the organization. Such screenings also can help determine at the time
      of admission whether a patient has a major medical complication or comorbidity,
      which--if undetected--could have serious payment implications.

PMID- 19743657
TI  - Put the brakes on accelerating variable rate debt before fiscal year-end.
AB  - Review variable rate debt agreements for subjective acceleration clauses--or MACs
      -that trigger debt as current. Talk to your auditors about how to address MACs
      before fiscal year-end. Negotiate alternative financing approaches with
      creditors.

PMID- 19743658
TI  - Hospitals are selling (EHR)--but will physicians buy?

PMID- 19743659
TI  - Your investment portfolio: will it be autopsy or biopsy?

PMID- 19743660
TI  - National trends in hospital quality measures.

PMID- 19743661
TI  - Credit crunch dentistry.

PMID- 19743662
TI  - Mastication and swallowing: 1. Functions, performance and mechanisms.
AB  - The process of mastication involves movements of the tongue, lips and cheeks as
      well as the more obvious actions of the teeth and jaws. In recent years there
      have been significant advances in our knowledge of the relationships between
      these movements in human beings and of how the processes of mastication are
      related to the associated events of swallowing. In this, the first of two papers,
      we review the role of mastication in food processing and nutrition and the effect
      of tooth loss on masticatory performance.The paper also reviews new information
      on masticatory and swallowing functions in human beings eating naturally. The
      review relates this knowledge to clinical dentistry, notably to the relevance of
      a good dentition to the digestive process and practical considerations in the
      replacement of missing teeth. CLINICAL RELEVANCE: Dentists should understand the
      process of mastication because an adequate dentition can facilitate the general
      health and well-being of their patients.This understanding can also inform the
      clinical management of patients with a depleted dentition or otherwise impaired
      masticatory system.

PMID- 19743663
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. CLINICAL RELEVANCE: Cracked tooth syndrome is a common
      occurrence in general dental practice and may be difficult to diagnose,
      especially as to the extent and direction of the crack. Awareness of cracked
      tooth syndrome is therefore important in providing the correct treatment and
      patient management.

PMID- 19743664
TI  - Nasal obstruction as the first symptom in a patient with a calcifying epithelial
      odontogenic tumour (CEOT).
AB  - Calcifying epithelial odontogenic tumour (CEOT), also known as Pindborg tumour,
      is a rare, benign odontogenic neoplasm. A case of an intra-osseous CEOT in the
      maxilla is presented in which unilateral nasal obstruction and progressive
      difficulty in breathing were the first clinical symptoms. Dental practitioners
      might be the first clinicians to come across such tumours, during investigation
      of missing or non-erupted maxillary teeth, ie canines, and they should be alerted
      by any unilateral nasal obstruction symptoms. Diagnostic features and treatment
      options of the tumour are discussed in relation to its histological typing.
      CLINICAL RELEVANCE: This manuscript highlights the importance of accurate
      clinical and radiographic investigation for the dental practitioner when
      assessing missing maxillary teeth.

PMID- 19743665
TI  - Sustained continuing education: how a masters programme makes a difference to
      primary care dentists.
AB  - Courses that are part of a longer-term planned programme of continuing education
      are more likely to impact on the practice of dentists than short course
      interventions.This study assessed the impact of a part-time, five-year Master of
      Science (MSc) programme at the School of Dentistry, University of Birmingham,
      designed specifically for general dental practitioners. Perceptions were sought
      from all 22 dentists registered on the MSc at the time of the study. The study
      provides evidence that a well-targeted masters programme for primary care
      dentists can make a difference to participants' knowledge and confidence and,
      importantly, generate change in practice. CLINICAL RELEVANCE: Sustained
      continuing education programmes, such as the University of Birmingham Masters
      Degree targeting primary care dentists, can provide valued contact with other
      dentists, and enhance practitioners' clinical knowledge.

PMID- 19743666
TI  - A single implant with tissue training in the aesthetic zone.
AB  - This paper presents a case study for replacing a single maxillary central incisor
      with a single implant, in conjunction with grafting lost hard and soft tissue.
      Using staged protocols, the maturity and stability of the implant was ensured
      prior to finalizing the case. In this respect, it was originally planned that a
      minimum healing period of nine months would be observed, but in fact the patient
      did not return for one year. Taking time to stage phases of the case and observe
      any changes provides an opportunity to evaluate each phase before the next step
      is carried forward. By staging the challenges faced in this case, the author was
      able to progress to each subsequent step with added assurance. By the time the
      final restorations were fitted, the graft and tissues were stable. The time
      involved not only placed biology on the clinician's side, but also helped the
      patient to spread the cost. CLINICAL RELEVANCE: In modern aesthetic dentistry
      harmonious results can be relatively quickly achieved when the prerequisites for
      aesthetic success have already been met but, as this case demonstrates, human
      biology often requires more time and patience for augmented hard and soft tissues
      to heal and mature.

PMID- 19743667
TI  - Inverted impaction of a mandibular premolar associated with a dentigerous cyst:
      report of a case.
AB  - Inverted impaction of mandibular premolars is reported to be rare; its prevalence
      has not been quantified. Here we report a case in which a 12-year-old female
      presented with an inverted impacted manibular premolar associated with a
      dentigerous cyst. The likely aetiology and management of this condition is
      discussed. CLINICAL RELEVANCE: This case highlights the need for clinicians to be
      aware of the rarer causes of apparent absence of teeth from the arch and the
      importance of taking radiographs prior to treatment planning.

PMID- 19743668
TI  - Hot topics in special care dentistry.

PMID- 19743669
TI  - Physical signs for the general dental practitioner. Case 66. Occupational eczema.

PMID- 19743671
TI  - No expenses spared special edition.

PMID- 19743670
TI  - Aspects of human disease. 35. Hyperthyroidism.

PMID- 19743672
TI  - The productive operating theatre programme.

PMID- 19743673
TI  - Five mile high club.

PMID- 19743674
TI  - Family witnessed resuscitation: an invitation to share your experiences.

PMID- 19743675
TI  - Is blowing the whistle on poor standards of care worth losing a career?

PMID- 19743676
TI  - Pain management: an adolescent scoliosis patient.
AB  - Recovery units can be busy environments not often conducive to reflective
      practice. Reflection is, however, an important aspect of high quality care. Using
      Gibbs model of reflection (see Figure 1), applied to the experience of caring for
      a 15 year old patient who had undergone surgery to correct a scoliosis deformity,
      this article illustrates how a deeper understanding of holistic pain management
      and assessment can be achieved and high standards of care maintained through
      careful reflective practice.

PMID- 19743677
TI  - Circulation and invasive monitoring: back to basics.

PMID- 19743678
TI  - Mentorship: the experiences of a tutor in a pre-registration operating department
      practice education programme.

PMID- 19743679
TI  - Perioperative use of antibiotics in elective surgical patients: timing of
      administration.
AB  - The practice of perioperative antibiotics administration in relation to surgical
      incision was analyzed in 525 elective surgical patients at St Vincent University
      Hospital, Dublin. 82.86 % (435) patients received the perioperative antibiotics
      before surgical incision was made and 17.14 % (90) patients received it after the
      surgical incision was made. The issue of timely administration of perioperative
      antibiotic should be included in the surgical time out to improve compliance in
      this regard.

PMID- 19743680
TI  - Dame Cicely Saunders OM DBe: founder of the hospice system.

PMID- 19743681
TI  - Gallup on trust.

PMID- 19743682
TI  - What the dental schools are doing to help with the access issue.

PMID- 19743683
TI  - An essay about an essay.

PMID- 19743684
TI  - The search for harmony and peace.

PMID- 19743685
TI  - Writing as a way of life.

PMID- 19743686
TI  - Meaning more than is being said.

PMID- 19743687
TI  - Academic integrity in dental school: a call to action.
AB  - Recently there has been much discussion in the media and literature pertaining to
      academic misconduct in higher education. Dentistry has not been immune to this
      discussion. Recent "scandals" involving student misconduct in U.S. dental schools
      have sparked dialogue within dentistry's premier professional organizations. The
      authors of this position paper recognize that academic misconduct can be a
      serious threat to dental education and the profession of dentistry as a whole.
      This paper addresses academic misconduct in dental school, the impact it may have
      on our profession, and how educators can begin to develop strategies to curtail
      cheating in their institutions.

PMID- 19743688
TI  - Enhancing professionalism using ethics education as part of a dental licensure
      board's disciplinary action. Part 1. An evidence-based process.
AB  - This paper describes a process and procedures for interacting with individuals
      who have violated the rules of professional conduct and includes descriptions of
      each of the assessment measures used to conduct a baseline assessment of four
      ethical capacities that are necessary conditions for reflective, ethical
      practice. The process and assessment methods are theoretically grounded in Rest's
      Four Component Model of Morality--a model that asserts that moral failing can
      result in a deficiency in any one of four abilities or capacities that are
      necessary for ethical behavior. Following descriptions of five well-validated
      assessment strategies, a synopsis of an educational intervention is presented.

PMID- 19743689
TI  - Assertiveness.
AB  - Assertiveness means speaking up for one's interpersonal freedoms or as required
      by one's role responsibilities to engage others in finding viable, stable
      solutions. Assertiveness is a learnable skill rather than a personality
      characteristic. The first step in assertiveness is recognizing the nature of
      one's problem in order to avoid the objectionable and usually ineffective
      practice of trying to solve other people's problems. A simple assertive approach
      is to suggest a solution. A more structured technique involves identifying the
      behavior that is causing a problem and expressing one's feelings about the
      problem (I-messages). The most powerful technique combines portions of suggested
      solutions and I-messages with a clear statement of consequences (DESC scripts).
      Although there may be a small number of circumstances where they are appropriate,
      acquiescence (temporarily forgoing one's interpersonal freedoms or role
      responsibilities) or aggression (insisting on one's own solution to the detriment
      of others) have several disadvantages. An example of justifiable criticism in the
      case of recognized gross or continuous faulty work by another dentist is
      presented.

PMID- 19743691
TI  - The Mifflin-Juniata Dental Clinic.

PMID- 19743692
TI  - Delegates get a taste of media training.

PMID- 19743693
TI  - President Gamba's Address to the House of Delegates.

PMID- 19743694
TI  - Dr. William G. Glecos receives PDA Distinguished Service Award.

PMID- 19743695
TI  - Chester-Delaware Give Kids a Smile Program honored with PDA Public Service Award.

PMID- 19743696
TI  - Dr. Elliot V. Hersh receives PDA Recognition Award.

PMID- 19743697
TI  - Dr. Andrew J. Kwasny, incoming President's Address to the House of Delegates.

PMID- 19743698
TI  - Meet your president, Dr. Andrew J. Kwasny.

PMID- 19743699
TI  - Red Flags Rule: are you compliant?

PMID- 19743700
TI  - Financial ratios.

PMID- 19743701
TI  - Healthcare reform and the stimulus package.

PMID- 19743702
TI  - Consumer-driven healthcare: essential points and players.

PMID- 19743703
TI  - The healthcare crisis: competition is the problem and the solution.
AB  - When judged by any responsible national or international criteria, the U.S.
      healthcare system has reached the point of crsis. Serious issues exist regarding
      access, quality, and costs of our present system. Previous reform efforts have
      not been successful in addressing these concerns. A true market-driven,
      comprehensive healthcare system incorporating appropriate elements of competition
      with respect to pricing and the quality of services, along with the availability
      of accurate, transparent, data-supported information, would offer a higher
      probability of success in dealing with the causes of our healthcare crisis than
      would a government-run, single-payor system.

PMID- 19743704
TI  - Internship logistics: successfully navigating the internship process.
AB  - This article, the second in the series, is designed to help medical practices
      understand how the internship process works. This article helps practice managers
      perform a needs analysis in order to determine if a student intern is
      appropriate, provides tools to help structure the internships and forms to
      evaluate the process, and identifies ways for the practice to avoid legal
      pitfalls when "employing" interns.

PMID- 19743705
TI  - Compliance issues for small and medium-size physician practices.
AB  - The purpose of this series of articles is to serve as a resource and guidance in
      the creation and implementation of a compliance program that includes a
      compliance plan and billing rules and regulations. This first part highlights why
      a written compliance plan is important for practices of all sizes.

PMID- 19743706
TI  - Working with children: a medical practice staff training tool.
AB  - The majority of medical practices have children visit them at least some of the
      time. The medical practice staff must be ready to work with the children who have
      appointments or who accompany adult patients. Knowing how to minimize
      confrontational situations and acting-out behavior with children will go a long
      way to maintaining a calm and pleasant office environment for everyone. This
      article explores the most common fears and concerns children have about visiting
      medical practices. It suggests specific ways the medical practice staff can coach
      parents and caregivers about a child's upcoming appointment. This article also
      offers 25 practical strategies the staff can use when working with the children
      who visit the practice, a checklist of items to discuss with children about an
      upcoming checkup, and 30 alternative ways to say "good job" to a child who visits
      the medical practice.

PMID- 19743707
TI  - Dealing with difficult patients.
AB  - Every physician and every practice is confronted with difficult patients. How a
      doctor and a practice manage these difficult patients will ultimately determine
      the success of the practice. This article will discuss how to recognize the
      difficult patient, how to treat the difficult patient using the three-step
      response, and what to do if the patient doesn't comply with the standards of the
      practice.

PMID- 19743708
TI  - Those maddening phones.

PMID- 19743709
TI  - Managing patients with high-deductible health plans and health savings accounts.
AB  - High-deductible health plans and health savings accounts have many patients and
      providers mutually mystified. It is very important for providers and their staff
      to understand and manage these emerging products. If the current growth rate of
      enrollment in these plans continues, 25% of your patients will be presenting with
      this coverage in fewer than six years. Mishandling these products can cause
      unnecessary cash flow issues, but a little proactivity, education, and training
      now, will go a long way.

PMID- 19743710
TI  - Questionable hospital financial relationships with physicians.
AB  - Hospital and physician financial relationships are coming under even more
      scrutiny by the Centers for Medicare & Medicaid Services (CMS) and the Office of
      Inspector General. Clearly, CMS intends to audit vastly more hospital-physician
      financial relationships as part of Stark compliance. CMS has already begun
      sending a Disclosure of Financial Relationship Report to 400 hospitals as part of
      enforcing the Deficit Reduction Act. Those hospitals that do not respond
      truthfully and promptly may be subject to noncompliance with a Medicare condition
      of participation and therefore ineligible to participate in the Medicare and
      Medicaid Programs.

PMID- 19743711
TI  - Adopting electronic medical records: what do the new federal incentives mean to
      your individual physician practice?
AB  - Under President Obama's American Recovery and Reinvestment Act of 2009, the
      federal government is offering incentives to physicians to adopt electronic
      health records. The goal is to improve quality of care and constrain costs.
      Higher incentive payments are available for those physicians who act quickly to
      meet the government's standards. Physicians who practice in "health professional
      shortage areas" and who serve mainly Medicaid recipients may qualify for
      additional incentives. Although compliance is "voluntary, "physicians who have
      not met the standards by 2015 will face reductions in their Medicare
      reimbursements unless they can show a significant hardship. Physicians can get
      started by contacting hospitals with which they are affiliated and professional
      associations to find out what vendors are being used in their service area.
      Agreements for electronic health records should be reviewed carefully to ensure
      that physicians' interests are protected.

PMID- 19743712
TI  - Restructuring primary care for performance improvement.
AB  - Primary care practices can no longer consider ongoing quality assessment and
      management processes to be optional. There are ever-increasing demands from any
      number of interested parties for objectively measured proof of outcomes and
      quality of care. Primary Care Partners (PCP), a 16-site ambulatory affiliate of
      the Spectrum Health system in Grand Rapids, Michigan, began such a continuous
      quality improvement (CQI) effort in 2005. The intent was to develop an ongoing
      systematic process that would raise its performance potential and improve patient
      outcomes in the areas of chronic disease management and preventive services. This
      article describes the partnerships PCP established, specific benchmarks and
      measurements used, processes utilized, and results to date. This could be used as
      a roadmap for other primary care systems that are working to establish CQI in
      their daily operations.

PMID- 19743713
TI  - Using computers in the exam room.
AB  - Purchasing an electronic health records system is the first step to assimilation
      of the new system into the fabric of a practice. The next hurdle is use of the
      electronic health record as close to the point of patient care as possible, which
      requires the clinician to use a computer. This article presents some of the
      unique challenges of using computers to document patient encounters and some
      practical advice and considerations for improving the use of computers at the
      bedside.

PMID- 19743714
TI  - COBRA subsidy update and court rulings on beneficiary designation conflict and
      revenue-sharing disclosure.

PMID- 19743715
TI  - Leasing physician office space.
AB  - When leasing office space, physicians should determine the effective lease rate
      (ELR) for each building they are considering before making a selection. The ELR
      is based on a number of factors, including building quality, building location,
      basic form of lease agreement, rent escalators and add-on factors in the lease,
      tenant improvement allowance, method of square footage measurement, quality of
      building management, and other variables. The ELR enables prospective physician
      tenants to accurately compare lease rates being quoted by building owners and to
      make leasing decisions based on objective criteria.

PMID- 19743717
TI  - Healthcare reform.

PMID- 19743716
TI  - Computer briefs: the smart home.

PMID- 19743718
TI  - What is your diagnosis? Perniosis (Chilblain).

PMID- 19743719
TI  - Multiple congenital plaquelike glomuvenous malformations with type 2 segmental
      involvement.
AB  - Multiple congenital glomuvenous malformations (GVMs) are rare. Almost all
      reported cases describe the multiple congenital plaquelike GVM variant. We report
      a case of multiple congenital plaquelike GVMs suggestive of type 2 segmental
      involvement following Blaschko lines.

PMID- 19743720
TI  - Botanical briefs: common ivy (Hedera helix).

PMID- 19743721
TI  - Minocycline-induced pigmentation mimicking persistent ecchymosis.
AB  - We report an unusual case of minocycline-induced pigmentation mimicking
      persistent ecchymosis in a patient with persistent (20 months' duration) bluish
      black discoloration of the medial and lateral aspects of the left ankle following
      an avulsion fracture. We review the common presentations of minocycline-induced
      pigmentation as well as some of the more unusual presentations.

PMID- 19743722
TI  - Cutaneous metastasis of uterine adenocarcinoma: a case report and review of the
      literature.
AB  - Cutaneous metastases from cancer are relatively uncommon in clinical practice but
      when present may herald the diagnosis of internal malignancy. The most common
      sources of primary cancer are the breasts, lungs, large bowel, oral cavity,
      kidneys, stomach, ovaries, and malignant melanoma. Despite the high incidence of
      uterine adenocarcinoma, cutaneous metastases are uncommon. The most common
      presentation of cutaneous metastases is rapidly developing nodules or tumors. The
      diagnosis of cutaneous metastatic carcinoma hinges on histopathologic evaluation
      of the involved skin. We discuss and review the diagnosis and management of
      cutaneous metastasis of uterine adenocarcinoma.

PMID- 19743723
TI  - The use of oral terbinafine or topical ciclopirox for lichen planus.

PMID- 19743724
TI  - Standard management options for rosacea, part 1: overview and broad spectrum of
      care.
AB  - The standard management options were developed by a consensus committee and
      review panel of 26 experts to assist in providing optimal patient care based on
      the standard classification and grading systems for rosacea that were developed
      to perform research; analyze results and compare data from different sources; and
      provide a common terminology and reference for the diagnosis, treatment, and
      assessment of results in clinical practice. We discuss standard management
      options for rosacea in 2 parts: (1) overview and broad spectrum of care, and (2)
      options according to subtype. The options are considered provisional and may be
      expanded and updated as appropriate. Managing the various potential signs and
      symptoms of rosacea calls for consideration of a broad spectrum of care, and a
      more precise selection of therapeutic options may become increasingly possible as
      the mechanism of action of therapies are more definitively established.

PMID- 19743726
TI  - Cooperative health engagement in stability operations and expanding partner
      capability and capacity.

PMID- 19743725
TI  - A 3-step acne system containing solubilized benzoyl peroxide versus clindamycin
      benzoyl peroxide.
AB  - A 3-step acne system has been developed to enhance the bioavailability and
      follicular penetration of benzoyl peroxide (BPO). Participants with mild to
      moderate facial acne vulgaris were randomly assigned to 10 weeks' facial
      treatment with the 3-step acne system (proprietary salicylic acid cleanser 2%
      twice daily, proprietary salicylic acid toner 2% once daily, and solubilized BPO
      gel 5% twice daily) or with control cleanser twice daily plus clindamycin 1%-BPO
      5% gel (jar formulation) twice daily. Among 139 participants enrolled, the 3-step
      acne system was at least as effective as clindamycin-BPO in reducing
      noninflammatory lesion counts in the early weeks of treatment in the absence of
      an antibiotic (mean reductions were 27% vs 13%, 39% vs 25%, 40% vs 33%, and 42%
      vs 42% at weeks 2, 4, 6, and 10, respectively) (all not significant). Both
      regimens were associated with comparable reductions in inflammatory lesion counts
      at all time points. Both regimens also were generally well-tolerated with mean
      scores for erythema, dryness, peeling, burning/stinging, and itching less than
      mild in both groups at all time points. The 3-step acne system is at least as
      effective as clindamycin-BPO in reducing noninflammatory lesion counts in the
      early weeks of treatment in the absence of an antibiotic, which is likely
      attributed to the solubilized BPO formulation.

PMID- 19743727
TI  - The lion, the doctor, and the omen: the importance of dissociation in the
      peritraumatic and immediate post-traumatic period in the development of PTSD.

PMID- 19743728
TI  - A public health role for Internet search engine query data?

PMID- 19743729
TI  - Trauma exposure, branch of service, and physical injury in relation to mental
      health among U.S. veterans returning from Iraq and Afghanistan.
AB  - Significant mental health symptoms are reported in troops deployed to Iraq and
      Afghanistan (OEF/OIF). Symptomatic troops are more likely to be discharged and
      become eligible for Department of Veterans Affairs (DVA) care. Prevalence and
      predictors of mental health symptoms were assessed in 339 OEF/OIF veterans and
      reservists registering at the San Diego DVA. Participants completed self-report
      questionnaires assessing combat exposure, posttraumatic stress disorder (PTSD)
      symptom frequency and severity, depression, and substance and alcohol abuse. A
      minority of participants (36%) did not screen positive for mental health
      symptoms; the remainder met threshold for caseness of PTSD, depression, or
      substance and alcohol abuse. Using a hierarchical logistic regression model,
      gender, age, race, and rank were not significantly related to PTSD caseness,
      whereas most recent branch of service and report of injury during combat were.
      Follow-up analyses revealed that trauma history and combat exposure varied by
      branch of service. Knowledge of base rates and vulnerability factors can aid in
      rapid detection of "at risk" individuals.

PMID- 19743730
TI  - PTSD subclusters and functional impairment in Kosovo peacekeepers.
AB  - Peacekeepers deployed to Kosovo (N = 203) were evaluated prospectively, before
      the mission (August 2000) and at postdeployment, on a number of mental health and
      functional impairment variables. We examined the association between PTSD symptom
      subclusters and three indicators of functional impairment using hierarchical
      regression analyses, controlling for PTSD symptoms before the mission, and
      history of prior trauma. In the first model, avoidance and hyperarousal symptoms
      uniquely predicted a conglomerate of functional impact outcomes (e.g.,
      employment, family relationships, social functioning). In the second model,
      emotional numbing was the only significant predictor of violent behaviors. In the
      third model, re-experiencing symptoms were the only significant predictor of
      alcohol abuse problems. Overall, the four PTSD subclusters are differentially
      associated with varying functional impairment outcomes, which is important to
      note for evaluation and treatment purposes for veterans returning from overseas
      deployments.

PMID- 19743731
TI  - Echelon I interventions and triage are effective and concordant with echelon II
      care in combat operations.
AB  - We describe identified injuries, effectiveness of treatment, and triage
      categories for combat casualties at echelon 1 from April 1 to June 30, 2005 from
      western Iraq. A total of 133 casualties were evaluated including 12 who were
      killed in action and 7 who died of wounds. A medic or corpsman treated 75% of the
      remaining patients, 9% were treated by bystanders, 2% were seen by a physician or
      physician assistant, and 15% administered self-aid. Most injuries (84%) were
      blast related. Commonly wounded regions were the head (47%), lower extremities
      (40%), upper extremities (22%), and back (11%). Common interventions included
      dressings (37%), splints (8%), and intramuscular morphine (8%). Field triage
      categories at echelon I and casualty evacuation categories at echelon II were
      congruent. No significant injuries were missed and there were no detrimental
      interventions. In conclusion, combat casualties were assessed, treated, and
      evacuated appropriately by echelon I providers during this time frame.

PMID- 19743732
TI  - Coordinating an interdisciplinary disease management conference on a military
      installation: collaboration between military and civilian communities, lessons
      learned.
AB  - The needs of individuals with chronic diseases or disabilities are similar
      whether within military or civilian communities. With finite resources and the
      continuing global war on terrorism, military treatment facilities (MTFs) may find
      collaborative, multidisciplinary, continuing education efforts with community
      agencies invaluable. Collaborative efforts that bring military and civilian
      communities together can result in innovative programs that offer cost-effective
      high-quality information to enhance the knowledge and skill level of military
      families, providers, and other professionals who provide services and care for
      military eligible beneficiaries. This article addresses the development and
      implementation of two major multidisciplinary disease management conferences at
      Naval Medical Center Portsmouth (NMCP), Virginia. It provides an overview of
      lessons learned in the areas of preplanning, team building, program development,
      implementation, and evaluation. Despite challenges, tremendous benefits may be
      reaped from efforts to include diverse target populations from military and
      civilian communities.

PMID- 19743733
TI  - Tobacco promotion to military personnel: "the plums are here to be plucked".
AB  - Smoking rates among military personnel are high, damaging health, decreasing
      short- and long-term troop readiness, and costing the Department of Defense
      (DOD). The military is an important market for the tobacco industry, which long
      targeted the military with cigarette promotions. Internal tobacco industry
      documents were examined to explore tobacco sponsorship of events targeted to
      military personnel. Evidence was found of more than 1,400 events held between
      1980 and 1997. In 1986, the DOD issued a directive forbidding such special
      promotions; however, with the frequently eager cooperation of military personnel,
      they continued for more than a decade, apparently ceasing only because of the
      restrictions of the Master Settlement Agreement. The U.S. military collaborated
      with the tobacco industry for decades, creating a military culture of smoking.
      Reversing that process will require strong policy establishing tobacco use as
      unmilitary.

PMID- 19743734
TI  - Professionalism in medicine: we should set the standard.
AB  - As military physicians we have a unique set of professional values that may
      differ from our civilian counterparts because we have both our professional
      responsibilities to our patients as well as our professional values as military
      officers. Our core military values provide a solid foundation to set the standard
      for professionalism in medicine. As educators for medical students, residents,
      and fellows we have an obligation to not only teach them the art of medicine but
      to mentor them as professional military officers. The objectives of this article
      are threefold: first to define professionalism, second to identify measurement
      tools, and finally to offer suggestions for documentation and remediation when
      problems of professionalism are identified among residents and fellows.

PMID- 19743735
TI  - Gender differences in the physical demands of British Army recruit training.
AB  - This study examined gender differences in the physical demands of British Army
      recruit training in 3 platoons with different gender compositions. Subjects wore
      heart rate monitors to measure cardiovascular strain and accelerometers to
      measure physical activity during weeks 1, 6, and 9 of the 12-week program. There
      was no difference in physical activity between platoons or genders (p > 0.05). In
      the mixed gender platoon, males operated at a lower cardiovascular strain than
      females (24 +/- 2 vs. 33 +/- 2% heart rate reserve (HRR), p < 0.001), probably
      because of their greater aerobic fitness (p < 0.001). Males in the mixed gender
      platoon experienced lower cardiovascular strain than the male-only platoon (24 +/
      2 vs. 33 +/- 2% HRR, p < 0.001). Females experienced the same degree of
      cardiovascular strain, irrespective of platoon (33 +/- 2 vs. 33 +/- 3% HRR, p =
      0.814). The additional cardiovascular strain experienced by female recruits may
      increase fatigue and predisposition to overuse musculoskeletal injury.

PMID- 19743736
TI  - Physician attire in the military setting: does it make a difference to our
      patients?
AB  - OBJECTIVE: To examine patient preference regarding physician attire and whether
      perception of medical competence was influenced by the physician's clothing
      style. METHODS: New patients presenting to the OB/GYN clinic at the Naval Medical
      Center Portsmouth were asked to complete a survey regarding patient preference
      for physcian attire and any effect on their comfort or confidence in the
      physician. RESULTS: Surveys were collected over a 2-month period. Completed
      surveys (328) were analyzed with the following results: 86% had no preference
      whether the physician wore a white coat, 61% preferred scrubs, 13% were
      uncomfortable talking to a doctor about general topics, and 16% were
      uncomfortable talking about sexual, psychological, or personal topics based on
      physician attire. In a comparison between active duty women and dependent wives,
      a significantly greater number of dependent wives reported the physician attire
      having no influence on their comfort level discussing general topics with their
      physician (p = 0.037) or about sexual, psychological, or personal topics (p =
      0.035). No difference was seen between groups in the preference to wear a white
      coat (p = 0.196) or other attire (p = 0.088) or of an influence of the doctors'
      clothing on the patient's confidence in the doctors' abilities (p = 0.063).
      CONCLUSION: Overall, female patients in a military setting do not have a
      preference for specific physician attire and attire does not influence their
      perception of the doctor's competence. However, a greater number of dependent
      wives report physician attire has no influence on their comfort level discussing
      both general and personal topics when compared with active duty women. This
      finding highlights the unique role of the military uniform in the eyes of active
      duty women and their potential discomfort in discussing personal medical issues
      with a physician in military uniform.

PMID- 19743737
TI  - Hydration status of Air Force military basic trainees after implementation of the
      back-mounted hydration system.
AB  - The Air Force makes an extraordinary effort to prevent heat-related illnesses
      associated with basic military training (BMT) in south Texas. However, inadequate
      hydration can still contribute to lost training time and qualified trainees
      leaving military service without completing BMT. The purpose of the present study
      was to determine whether equipping BMTs with back-mounted hydration systems (BM)
      is better than the standard-issue (SI) canteens with respect to hydration status.
      Male BMTs were randomly assigned to either BM (n = 40) or SI (n = 38) groups.
      Baseline values were assessed at week 0 before any physical readiness training
      (PRT). Subsequent data collection took place in the a.m. before PRT and in the
      p.m. before dinner the first 3 weeks, and during the 5 weeks of training. BMT
      total body water (TBW) and body composition were assessed by bioelectrical
      impedance. Saliva osmolality and total protein concentration were also
      determined. Hydration status increased daily in BM and SI and was well maintained
      over the duration of BMT. A significant hydration effect (p < 0.05) was observed
      for average daily increases in TBW and body weight with BM gaining more compared
      to SI. Average a.m. TBW was 0.3-0.8 L greater in SI versus BM (p < 0.05). Our
      findings demonstrate that adequate hydration status is maintained during Air
      Force BMT in a hot environment using either hydration mode and therefore do not
      support widespread issuance of the BM system on the premise of improved hydration
      during USAF BMT military training.

PMID- 19743738
TI  - Intoxication with mouthwash presenting as psychosis and delirium in a combat
      theater.
AB  - Alcohol is prohibited in combat zones, but it still can be obtained via covert
      sources. This can cause complex issues for the military physician. We present a
      case of a U.S. Marine in Iraq who was noted to have intermittent and unexplained
      behavioral changes. The patient had repeatedly denied alcohol use, but during a
      second medical evacuation from theater, a blood alcohol level was drawn. Results
      did not come back fast enough to prevent the evacuation, but did eventually
      confirm that he was intoxicated. Mouthwash was the source. This case illustrates
      the importance of screening for alcohol abuse and intoxication even in situations
      in which conventional use of alcohol is not anticipated.

PMID- 19743739
TI  - Does foot pitch at ground contact affect parachute landing technique?
AB  - The Australian Defence Force Parachute Training School instructs trainees to make
      initial ground contact using a flat foot whereas United States paratroopers are
      taught to contact the ground with the ball of the foot first. This study aimed to
      determine whether differences in foot pitch affected parachute landing technique.
      Kinematic, ground reaction force and electromyographic data were analyzed for 28
      parachutists who performed parachute landings (vertical descent velocity = 3.4 m
      x s(-1)) from a monorail apparatus. Independent t-tests were used to determine
      significant (p < 0.05) differences between variables characterizing foot pitch.
      Subjects who landed flat-footed displayed less knee and ankle flexion, sustained
      higher peak ground reaction forces, and took less time to reach peak force than
      those who landed on the balls of their feet. Although forefoot landings lowered
      ground reaction forces compared to landing flat-footed, further research is
      required to confirm whether this is a safer parachute landing strategy.

PMID- 19743740
TI  - Shortening and angulation for soft-tissue reconstruction of extremity wounds in a
      combat support hospital.
AB  - BACKGROUND: Bone and soft-tissue loss are common extremity injuries sustained in
      current military conflicts. Selected host national patients had their definitive
      orthopedic care performed at our combat support hospital. Soft-tissue
      reconstruction can be a challenging task in this environment. There are several
      situations in which free or rotational flap coverage is not possible, including
      the presence of a single vessel limb, local muscle damage, and/or nonavailability
      of an experienced flap surgeon. The technique of shortening and angulation for
      extremity soft-tissue reconstruction is described using tools available in a
      theater of operations. METHODS: We treated 6 limbs in 5 patients with the
      technique of shortening and/or angulation to obtain soft-tissue coverage for
      extremity war wounds at our combat support hospital. Bony stabilization was
      accomplished using the standard Hoffman II external fixator (Stryker Orthopedics,
      Mahwah, NJ). The extremities treated included: 2 humerus fractures, 3 tibia
      fractures, and 1 ankle fracture. Two of the patients required vascular
      reconstruction. Patients were followed for as long as possible given individual
      circumstances. RESULTS: One patient in the series died of multiple organ system
      failure because of intra-abdominal injuries. Average follow-up on the remaining
      patients was 7.03 weeks (1 to 14 weeks). In the patient with 1-week follow-up,
      the skin graft had 100% take. All other wounds were healed at the latest follow
      up without signs of infection. CONCLUSION: Shortening and/or angulation of
      extremities with bone and soft-tissue loss is an effective means of obtaining
      soft-tissue coverage in a theater of operations.

PMID- 19743741
TI  - Mortality among United States Coast Guard marine inspectors: a follow up.
AB  - We previously assessed mortality among U.S. Coast Guard (USCG) marine inspectors
      (inspectors) and Coast Guard officers who were not marine inspectors
      (noninspectors). Here, we extended follow-up of the cohort by 14 years,
      ascertaining vital status 1980-1994, calculating standardized mortality ratios
      (SMRs) for inspectors and noninspectors, and comparing mortality rates via
      directly adjusted rate ratios (RRs). Both inspectors and noninspectors had
      deficits for all causes of death (SMR = 75 and 61, respectively) and all
      malignant neoplasms (SMR = 86 and 69, respectively). Compared with noninspectors,
      inspectors had nonstatistically significant excesses of liver cirrhosis (SMR =
      124; RR = 2.2) and chronic rheumatic heart disease (SMR = 129; RR = 2.6) and
      deficits of cancer of the respiratory system (SMR = 59; RR = 0.8). SMRs and RRs
      rose with increasing probability of exposure to chemicals for cirrhosis of the
      liver, all accidents and motor vehicle accidents, although they fell for all
      causes of death, diseases of the nervous system, diseases of the circulatory
      system, and cancers of the respiratory system. These results suggest that contact
      with chemicals during inspection of merchant vessels may be involved in the
      development of these diseases, although other aspects of the job, such as
      physical activity may account for deficits in respiratory cancers.

PMID- 19743742
TI  - Reproducibility and validity of a semiquantitative food frequency questionnaire
      among military men.
AB  - OBJECTIVE: A food frequency questionnaire (SFFQ) was developed to rank military
      men in tertiles of nutritional intake. DESIGN: validation study. SUBJECTS: 95
      military men. MRTHODS: two SFFQ's (SFFQ1 and SFFQ2) were collected with 2-week
      intervals. Four-day dietary records (4DDRs) were collected between the SFFQs.
      RESULTS: the correlation coefficients for energy adjusted nutrients between SFFQ1
      and SFFQ2 ranged between 0.42 (vitamin A) to 0.79 (total energy intake). The
      correlation coefficients between SFFQ1 and 4DDR ranged from 0.05 (vitamin A) to
      0.50 (total energy intake). The correlation coefficients between SFFQ2 and 4DDR
      ranged from 0.01 (vitamin A) to 0.52 (total energy intake). The percentage of
      individuals classified in the same tertile comparing SFFQ1 and 4DDR ranged from
      33.7% (vitamin A) to 52.6% (total alcohol intake). CONCLUSION: our SFFQ has a
      good reproducibility and an acceptable validity to rank individuals according to
      dietary intake.

PMID- 19743743
TI  - Central nervous system manifestations of Q fever responsive to steroids.
AB  - We report the clinical and radiological central nervous system manifestations of
      a 27-year-old man with Q fever who subsequently developed acute disseminated
      encephalomyelitis and showed a significant response to steroids. The patient
      presented with headache and fever and quickly progressed to develop acute
      respiratory failure and hepatitis. A prompt evaluation revealed positive serology
      for Q fever and doxycycline was initiated. Approximately 1 week into his illness
      he was noted to be profoundly weak. Neuroimaging with magnetic resonance imaging
      (MRI) revealed diffuse white matter T2/FLAIR hyperintensities, with evidence of
      restricted diffusion. He was given high-dose steroids for a presumed diagnosis of
      acute disseminated encephalomyelitis (ADEM) and within days he had both clinical
      and MRI improvement. In addition to well-described meningitis and encephalitis, Q
      fever may also be associated with diffuse CNS lesions that may be demyelinating
      inflammatory in pathophysiology, and therefore responsive to high-dose steroids.

PMID- 19743744
TI  - Species distribution and in vitro susceptibility of Candida bloodstream isolates
      to six new and current antifungal agents in a Turkish tertiary care military
      hospital, recovered through 2001 and 2006.
AB  - OBJECTIVE: Species distribution and antifungal susceptibility of Candida
      bloodstream isolates. METHODS: 173 Candida species recovered from fungemic
      patients admitted to the largest tertiary-care military hospital between 2001 and
      2006 in Ankara, Turkey evaluated retrospectively. Antifungal susceptibility of 95
      isolates (45 Candida parapsilosis, 35 C. albicans, 7 C. tropicalis, 4 C. krusei,
      3 C. glabrata, and 1 C. kefyr) was determined against fluconazole, itraconazole,
      voriconazole, posaconazole, caspofungin, and amphotericin B. RESULTS: C. albicans
      was the most common yeast (48.0%), followed by C. parapsilosis. Almost all
      strains showed low minimal inhibitory concentration (MIC) values to all six
      antifungals tested. Only 2 of 45 C. parapsilosis isolates were resistant to
      fluconazole, one was susceptible in a dose-dependent manner (SDD) to
      itraconazole, and 14 were nonsusceptible to caspofungin. CONCLUSIONS: Increasing
      prevalence of C. parapsilosis emphasizes a need for better catheter care and
      continuous surveillance programs.

PMID- 19743745
TI  - Non-re-entrant atrioventricular nodal tachycardia.
AB  - Supraventricular tachycardia caused by AV nodal dual conduction is usually re
      entry tachycardia. We report a case of a 40-year-old man with incessant
      supraventricular tachycardia caused by simultaneous conduction via slow and fast
      AV nodal pathway. The patient was successfully treated with catheter ablation of
      slow AV nodal pathway, the treatment of choice of this form of tachycardia (when
      proper diagnosis is made). Analysis of previously published cases is discussed.

PMID- 19743746
TI  - Endovascular versus open management of blunt traumatic aortic disruption at two
      military trauma centers: comparison of in-hospital variables.
AB  - BACKGROUND: Blunt traumatic aortic disruption (BTAD) carries significant
      mortality and morbidity. Traditional open repair has appreciable risks of
      perioperative mortality and spinal cord ischemic complications. Endovascular
      repair may reduce the incidence of these adverse outcomes. We present the
      experience at two military trauma centers with thoracic aortic endografting for
      trauma (TAET) and compare this with recent open experience. METHODS: A review of
      inpatient records was performed. All patients undergoing open repair or TAET for
      acute BTAD were studied. Collected data included demographics, injury
      characteristics, and in-hospital variables. Descriptive statistics were
      calculated with two-tailed t-tests performed for comparison of continuous
      variables. RESULTS: Five open and eight TAET repairs were performed. Mean age was
      32 years (range 28-50) in the TAET group and 35 (25-57) in the open group. All
      patients, except one TAET, had at least one associated injury with thoracic
      injuries predominating. Twelve BTAD were just distal to the left subclavian
      artery. One injury, treated with TAET, was just proximal to the celiac. Operative
      blood loss averaged 298 +/- 394 mL in the TAET group vs. 2,400 +/- 3,800 mL in
      the open group (p = 0.18). Crystalloid infusions were similarly reduced in TAET
      patients, 1,019 +/- 532 mL vs. 4,860 +/- 1,547 mL, p < 0.05), as were red blood
      cell transfusions, 1.6 units vs. 5.0 units (p = 0.12). The majority of patients
      [6/8 (75%) TAET, 5/5 (100%) open] experienced an inpatient complication (p =
      0.09). All open patients had at least one infectious complication. There were no
      inpatient deaths related to aortic injury or spinal cord ischemic complications.
      CONCLUSIONS: TAET is feasible for the treatment of BTAD in military trauma
      centers. It is important for military centers to accomplish this with adequate
      results as endovascular technologies are now being taken to the battlefield.
      Decreased blood loss and resuscitation requirements compared to open repair are
      likely contributors to improved outcomes with TAET.

PMID- 19743747
TI  - Is there still a benefit to operate appendiceal abscess on board French nuclear
      submarines?
AB  - Appendicular abscess occurred in 14.2% of patients presenting acute appendicitis.
      Management of these patients remains controversial, ranging from an emergency
      appendectomy to a nonoperative treatment. On board French nuclear submarines, the
      usual treatment for all cases of appendiceal masses, including both appendicitis
      and appendiceal abscess, is an appendectomy. In the past 5 years, the
      introduction of ultrasonography (US) on board has enabled the diagnosis of
      appendiceal abscess with a high rate of accuracy, and the latest studies show
      that nonoperative treatment is an alternative approach. This nonsurgical
      treatment, based on intravenous administration of antibiotics, is successful in
      about 93% of the patients. Failure of nonsurgical treatment is a reliable
      indication of percutaneous drainage. The proportion of adult patients who need
      percutaneous drainage of abscesses is about 27%. A successful primary
      nonoperative treatment may or may not be followed by interval appendectomy at the
      conclusion of the patrol. Nonsurgical treatment is associated with a
      significantly lower morbidity than surgery. Considering that the on-board
      surgical facility is limited, nonsurgical treatment appears to be the best
      approach for treating a sailor with an appendiceal abscess during a submarine
      patrol mission.

PMID- 19743748
TI  - Cerebral air embolism following removal of central venous catheter.
AB  - Cerebral air embolism occurs very seldom as a complication of central venous
      catheterization. We report a 57-year-old female with cerebral air embolism
      secondary to removal of a central venous catheter (CVC). The patient was treated
      with supportive measures and recovered well with minimal long-term injury. The
      prevention of air embolism related to central venous catheterization is
      discussed.

PMID- 19743749
TI  - Radiology corner. Case (# 38) and image: testicular torsion.

PMID- 19743750
TI  - Advancing the science of understanding and improving the health of the
      population.

PMID- 19743751
TI  - The evolution of the Department of Population Health Sciences.

PMID- 19743752
TI  - Managing type 1 diabetes: trends and outcomes over 20 years in the Wisconsin
      Diabetes Registry cohort.
AB  - CONTEXT: The Wisconsin Diabetes Registry Study is a Wisconsin cohort of patients
      with type 1 diabetes, who were diagnosed in 1987-1992 and actively followed. The
      study provides patients and health care professionals with better prognostic
      information and helps identify aspects of diabetes management that need
      improvement. OBJECTIVE: To describe diabetes management and acute and chronic
      complications from the time of diagnosis. DESIGN AND SETTING: All incident cases
      diagnosed at age <30 in 28 counties were eligible and 590 enrolled. A baseline
      interview, blood sample kits, biannual/annual questionnaires and study
      examinations at 4, 7, 9, 14, and 20 years duration were administered. MAIN
      OUTCOME MEASURES: Diabetes management indicators, general health, and acute and
      chronic complications. RESULTS: Glycemic control was poor in adolescence, but
      improved with age. A high percentage of individuals do not meet treatment
      standards for blood pressure and lipid profile. Self-reported health deteriorated
      with age, and body mass index was similar to that of the general US population.
      Chronic complications were present at 15-20 years, but tended to be relatively
      mild. CONCLUSION: There is room for improvement in diabetes management,
      especially in meeting goals for blood pressure and lipid profile. Nonetheless,
      individuals with type 1 diabetes can be offered a more optimistic prognosis than
      in the past.

PMID- 19743753
TI  - Dissemination research: the University of Wisconsin Population Health Institute.
AB  - Despite significant accomplishments in basic, clinical, and population health
      research, a wide gap persists between research discoveries (ie, what we know) and
      actual practice (ie, what we do). The University of Wisconsin Population Health
      Institute (Institute) researchers study the process and outcomes of disseminating
      evidence-based public health programs and policies into practice. This paper
      briefly describes the approach and experience of the Institute's programs in
      population health assessment, health policy, program evaluation, and education
      and training. An essential component of this dissemination research program is
      the active engagement of the practitioners and policymakers. Each of the
      Institute's programs conducts data collection, analysis, education, and dialogue
      with practitioners that is closely tied to the planning, implementation, and
      evaluation of programs and policies. Our approach involves a reciprocal exchange
      of knowledge with non-academic partners, such that research informs practice and
      practice informs research. Dissemination research serves an important role along
      the continuum of research and is increasingly recognized as an important way to
      improve population health by accelerating the translation of research into
      practice.

PMID- 19743754
TI  - A family perspective on population health: the case of child health and the
      family.
AB  - CONTEXT: This paper makes the case for a family perspective on population health
      and specifically focuses on how children's health can impact family health and
      well-being. OBJECTIVE: To review and synthesize the diverse set of papers that
      has examined the associations and linkages between children's health and family
      health. RESULTS: Based on the synthesis of the existing literature, additional
      research is needed that focuses on (1) the longitudinal impact of childhood
      chronic illness on the family using national samples, (2) the application of
      interdisciplinary methodologies to studying childhood chronic illness in the
      family, and (3) understanding the psychobiology of caring for a child with a
      chronic illness and the concordance of such measures with self-reported stress
      and burden. CONCLUSIONS: We propose a new integrated conceptual framework for
      better understanding the mechanisms that influence children's health and health
      care.

PMID- 19743755
TI  - Burden of sleep apnea: rationale, design, and major findings of the Wisconsin
      Sleep Cohort study.
AB  - CONTEXT: Untreated sleep apnea is a prevalent but treatable condition of
      breathing pauses during sleep. With approximately 15% of the US population
      affected, understanding of the total health burden is necessary to guide policy,
      population initiatives, and clinical practice to reduce the prevalence of this
      condition. OBJECTIVE: To outline the history and need for a population approach
      to understanding sleep apnea and provide a review of the first longitudinal
      population study of this disorder. DATA SOURCE: The results of cross-sectional
      and longitudinal data from 1500 participants in the Wisconsin Sleep Cohort,
      initiated 2 decades ago, illustrate the population burden of sleep apnea.
      RESULTS: The prevalence of sleep apnea is increasing with trends of increased
      obesity. Prospective findings from 4- to 15-year follow-up data indicate
      untreated sleep apnea predicts increased blood pressure, hypertension, stroke,
      depression, and mortality. CONCLUSIONS: The high prevalence of untreated sleep
      apnea and links to serious morbidity and mortality underscore the population
      burden of this condition and the need for greater clinical recognition and
      strategies to reduce prevalence.

PMID- 19743756
TI  - Association of blood and hair mercury with blood pressure and vascular
      reactivity.
AB  - BACKGROUND: Some studies suggest that high levels of blood and hair mercury (Hg)
      increase the risk of atherothrombotic diseases, an effect that may be explained
      by oxidative damage to the vascular endothelium. OBJECTIVES: We tested whether
      high Hg levels impair the vasodilating function of the vascular endothelium or
      increase blood pressure. METHODS: We measured the association between high blood
      and hair Hg and brachial artery flow mediated vasodilation (FMD%), middle
      cerebral artery reactivity to CO2 (MCAR%) and hypertensive status in 101
      participants in the Wisconsin Sleep Cohort Study (mean age of 59.4 years; 52.5%
      male). Whole blood total Hg and hair total Hg were tested using inductively
      coupled plasma mass spectrometry and cold vapor atomic fluorescence spectrometry,
      respectively. RESULTS: Geometric mean blood and hair Hg were 1.16 microg/L and
      270.1 ng/g. Blood and hair Hg were not significantly associated with FMD% and
      MCAR%. However, after adjustment for other risk factors, people in the upper
      quartile of blood Hg were 1.9 times (P=0.23) more likely to be hypertensive and
      those in the upper quartile of hair Hg were more than 4 times more likely
      (P=0.02). CONCLUSION: High hair and blood Hg levels do not seem to influence
      vascular reactivity, but may increase the risk of hypertension.

PMID- 19743757
TI  - Socioeconomic disparity in the prevalence of autism spectrum disorder in
      Wisconsin.
AB  - BACKGROUND: The number of children receiving services for autism spectrum
      disorders in Wisconsin and nationally has steadily increased in recent years. The
      Wisconsin Surveillance of Autism and Other Developmental Disabilities System was
      developed to study the prevalence of and risk factors for autism spectrum
      disorders. This analysis of Wisconsin surveillance data examined whether autism
      prevalence is positively associated with socioeconomic status. METHODS:
      Surveillance methods developed by the Centers for Disease Control and Prevention
      were used to determine the number of 8-year-old children with an autism spectrum
      disorder in a 10-county area of southeastern Wisconsin in 2002. Socioeconomic
      status quintiles were created based on census block group indicators. Autism
      prevalence was computed for each socioeconomic status quintile of the population.
      RESULTS: Using educational attainment as an indicator of socioeconomic status,
      autism spectrum disorder prevalence increased from 2.6 per 1000 in the lowest to
      6.8 per 1000 in the highest education quintile. The prevalence ratio for the
      highest to lowest education quintile was 2.6:1 (95% confidence interval: 1.6,
      4.5). Using median household income as an indicator of socioeconomic status
      produced similar results. CONCLUSION: Autism spectrum disorder prevalence is
      positively associated with socioeconomic status based on population-based
      surveillance in Wisconsin.

PMID- 19743758
TI  - Syndromic surveillance: early results from the MARISSA project.
AB  - CONTEXT: The Madison Area Review of Systems Syndromic Surveillance Application
      (MARISSA) project is the ongoing development of a syndromic surveillance system
      at the University of Wisconsin Hospital and Clinics Emergency Department. Readily
      available electronic health data will be used to provide timely identification of
      increased respiratory illness activity in the Madison area. OBJECTIVE: To develop
      novel data sets and statistical methods for syndromic surveillance. DESIGN: Time
      series of daily counts of influenza-like illness (ILI) and fever in the
      University of Wisconsin Hospital and Clinics Emergency Department from June 13,
      2007 to June 11, 2008. MAIN OUTCOME MEASURES: Operating characteristics of
      limited baseline aberration detection methods with varying lengths of baseline
      periods were evaluated by simulation. RESULTS: All methods had false detection
      rates at or below the nominal levels. True detection rates were substantially
      higher for methods based on longer baseline periods. CONCLUSION: The MARISSA
      project has adopted a limited baseline aberration detection method with a
      baseline period of 21 days and a nominal false alarm rate of once every 365 days
      for ongoing syndromic surveillance. Future work will explore the utility of novel
      data sources such as review of systems and vital signs for syndromic
      surveillance.

PMID- 19743759
TI  - Using lay health advisors to promote breast and cervical cancer screening among
      Latinas: a review.
AB  - CONTEXT: Breast and cervical cancer (BCC) represent leading causes of morbidity
      and mortality among Latinas. The use of lay health advisors (LHAs) represents a
      promising approach for health promotion among underserved and minority
      populations. OBJECTIVE: This study reviews the evidence regarding the
      effectiveness of LHA-based interventions to promote BCC screening among Latinas.
      METHODS: A search was conducted using the PubMed online electronic database. The
      search included studies published through August 2008. Study abstracts were
      reviewed to select intervention studies that met our inclusion criteria.
      References in selected articles were also reviewed for inclusion in the review.
      Of 134 articles identified, 14 met the selection criteria. The main
      characteristics and results of each study were extracted using a pre-established
      template. RESULTS: Most studies were conducted in the west or southwest regions
      of the United States. Few studies were guided by health behavior theory. Most
      studies used weak methodological designs, lacked a comparison group, and/or
      failed to collect both pretest and post-test data. Only 2 studies found evidence
      of effectiveness. CONCLUSIONS: More intervention research guided by health
      behavior theory and using rigorous methods is needed to elucidate the potential
      effectiveness of LHA interventions to promote BCC screening among Latinas.

PMID- 19743760
TI  - Sleep disordered breathing and metabolic syndrome.
AB  - BACKGROUND: Sleep disordered breathing (SDB) has been associated with
      cardiovascular disease, hypertension, and insulin resistance. This article
      examines the association between SDB and the prevalence of metabolic syndrome
      (MS) in a community-based sample. METHODS: A subset of participants in the
      Wisconsin Sleep Cohort Study (N=546) participated in an ancillary study to
      measure vascular and metabolic function. SDB was characterized using the apnea
      hypopnea index (AHI) obtained in the polysomnography study closest to the
      collection of the metabolic measures. MS was defined using the National
      Cholesterol Education Program definition, and the homeostasis model assessment
      method (HOMA) was used to characterize insulin resistance. RESULTS: SDB was
      significantly correlated with insulin resistance (Spearman r correlation between
      AHI and HOMA=0.30, P<0.0001). Compared with those without SDB (AHI <5), the age
      sex-adjusted odds ratios of MS associated with mild (AHA 5-14.9) and
      moderate/severe SDB (AHI > or = 15 or CPAP) were 4.0 (95% CI 2.6, 6.3) and 5.3
      (95% CI 3.2, 8.8), respectively. Additional adjustment for markers of sympathetic
      or neuroendocrine activation (urinary norepinephrine, cortisol, heart rate
      variability) did not materially alter these estimates. These associations were
      weaker but remained statistically significant after adjusting for body mass
      index. CONCLUSION: SDB might be considered an integral component of MS.

PMID- 19743761
TI  - Parametric models for studying time to antiretroviral resistance associated with
      illicit drug use.
AB  - OBJECTIVE: Biomedical researchers tend to choose semiparametric methods to model
      time-to-event data because they do not require any assumptions about the shape of
      the underlying hazard. An example is provided where parametric models are a
      desirable alternative. METHODS: Data were analyzed from a prospective cohort
      study of 195 adults receiving HIV care and highly active antiretroviral therapy
      in Baltimore, Md. They were followed for 1188 visits between February 2000 and
      December 2001. Kaplan-Meier estimation and Cox and Weibull regressions were
      performed. RESULTS: Illicit drug users experienced a greater hazard of clinically
      significant antiretroviral resistance as compared to non-users. Weibull
      regression demonstrated that a quarter and a half of illicit drug users developed
      resistance within 5 and 20 months of viral suppression, respectively, compared to
      20 and 85 months, respectively, for non-users. CONCLUSIONS: Both semiparametric
      and parametric methods demonstrated an increased hazard of clinically significant
      resistance associated with illicit drug use. The parametric model facilitated the
      estimation of elapsed time to resistance associated with illicit drug use.

PMID- 19743762
TI  - Modeling physician practice change using the Integrated Systems Model.

PMID- 19743763
TI  - From preventive medicine to population health: the research agenda of the
      Wisconsin State Laboratory of Hygiene.

PMID- 19743764
TI  - Population-based epidemiologic studies of aging: the contributions of a Wisconsin
      community.

PMID- 19743765
TI  - Genetic architecture of vitamin D.

PMID- 19743766
TI  - The Health and Society Scholars Program at the University of Wisconsin-Madison.

PMID- 19743767
TI  - Health economics at UW-Madison and the Department of Population Health Sciences.

PMID- 19743768
TI  - Using the tools of new governance to advance cancer detection, care, and
      survivorship.

PMID- 19743769
TI  - Factors affecting global environmental public health.

PMID- 19743770
TI  - Using biomarkers of aging to identify modifiable mechanisms underlying age
      related risk for cancer.

PMID- 19743771
TI  - Introduction to 'type 2' translational research.

PMID- 19743772
TI  - Epidemiologic breast cancer research at the UW-Madison: a summary of past
      accomplishments and future directions.

PMID- 19743773
TI  - The delay of preventive medicine for asbestos caused disease in the 20th century.

PMID- 19743774
TI  - Unwanted pregnancy and it's impact on maternal health and utilization of health
      services in Tigray Region (Adigrat Hospital).
AB  - BACKGROUND: Unwanted pregnancy is associated with increased risk of maternal
      mortality and morbidity. Knowledge of the causes and its impact on maternal
      health and utilization of health services is crucial to develop preventive
      strategies. OBJECTIVE: To assess possible factors of unwanted pregnancy and its
      impact on maternal health and utilization of health services. METHODS: This is a
      prospective study (February 1, 2002-January 31, 2004) conducted on patients with
      diagnosis of abortion and admitted to gynecological ward of a zonal hospital.
      RESULTS: Totally 907 patients were admitted with a diagnosis of abortion which
      accounted for 12.6% of all hospital and 60.6% of gynecological admissions.
      Majority (69.8%) had unwanted pregnancy. Interference was reported in 81.4% of
      unwanted pregnancy. More than 95% of patients with wanted and 74.9% of unwanted
      pregnancies reported to the hospital within 3 days of vaginal bleeding (P <
      0.0001). High incidence of complication was reported on patients with unwanted
      pregnancy. There were three maternal deaths and all were related to unwanted
      pregnancy. The mean hospital stay was 1.42 days in wanted and 2.06 days in
      unwanted pregnancies. Forced sex and failure of contraception were among the
      reasons for unwanted pregnancy. CONCLUSION: Unwanted pregnancy is associated with
      increased risk of maternal morbidity and mortality. Besides, it poses a burden to
      the utilization of health services. The development and prompt implementation of
      a strategy, that enables to safely manage unwanted pregnancy in recommended.

PMID- 19743775
TI  - Malnutrition and intestinal parasitic infections in school children of Gondar,
      North West Ethiopia.
AB  - BACKGROUND: In developing countries, malnutrition is a considerable health
      problem with prevalence ranges of 4-46%, with 1-10% severely malnourished.
      OBJECTIVES: This study aimed to determine the prevalence of malnutrition and
      intestinal parasitoses and identify risk factors of malnutrition in
      schoolchildren. SUBJECTS AND METHODS: A cross-sectional study was carried out on
      322 schoolchildren, of age 6 to 14 years, attending private and government
      primary schools, in Gonder town, North West Ethiopia. The study was conducted
      from December 2006 to February 2007. Nutritional status of these children was
      determined using anthropometric parameters (weight-for-age, height-for-age and
      weight-for-height). Epi Info 2000 software was used to evaluate anthropometric
      results of each individual and formol-ether concentration technique was employed
      to identify parasites. RESULTS: The prevalence of underweight, stunting, wasting
      and intestinal parasitoses was 34.8%, 27%, 50% and 55.6%, respectively. Parasites
      encountered during the study were Ascaris lumbricoides (17.8%), Trichuiris
      trichiura (3.4%), hookworm (4.3%), Giardia lamblia (9%), Entamoeba histolytica
      (2.1%), Schistosoma mansoni (2.4%), Hymenolepis nana (4.7%) and Enterobius
      vermicularis (0.31%), respectively, in single infections. Only two cases of
      Strongyloides stercoralis was found in multiple infections and none in single
      infections. The prevalence of multiple parasitoses was 10.9%. Maternal literacy
      status, sex and age of the child were significantly associated with malnutrition
      (p < 0.05). CONCLUSION: Even though chronic type of malnutrition (stunting) was
      decreasing, indicators of acute type of malnutrition were increasing at a higher
      rate in the area. Implementation of maternal education and school feeding
      programs, avoidance of students from getting in contact with waste and river
      water were recommended to avoid malnutrition and intestinal parasitoses in
      children of the study area.

PMID- 19743776
TI  - Prevalence of smear negative pulmonary tuberculosis among patients visiting St.
      Peter's Tuberculosis Specialized Hospital, Addis Ababa, Ethiopia.
AB  - BACKGROUND: Smear negative pulmonary tuberculosis is an increasing clinical and
      epidemiological problem, particularly in areas that are affected by the dual
      tuberculosis/Human immunodeficiency Virus infections. OBJECTIVE: This study was
      initiated to investigate the value of clinical parameters, chest x-ray findings
      and culture in the diagnosis of smear negative pulmonary tuberculosis. DESIGN: A
      cross sectional study was conducted among suspected pulmonary tuberculosis
      patients visiting St. Peter Tuberculosis Specialized Hospital, Addis Ababa,
      Ethiopia between November 15, 2004 and October 30, 2005. METHODS: A total of 297
      informed and consented patients with suspected pulmonary tuberculosis were
      screened for acid fact bacilli by direct smear microscopy. All smear negative
      pooled sputum samples were further processed for culture using conventional
      Lowenstein-Jensen solid medium and automated BACTEC MGIT 960 system liquid medium
      at the Ethiopian Health and Nutrition Research Institute. RESULTS: 247/297
      (83.2%) patents with suspected pulmonary tuberculosis have had a negative smear
      results for acid fast bacilli. Abnormal chest x-ray findings were observed in 196
      (79.4%) patients. 43/247 (17.4%) patients whose smears were negative for acid
      fast bacilli found to be positive for mycobacterial culture. The Mycobacterium
      species identified were M. tuberculosis (n = 40) (93%) and non-tuberculous
      mycobacteria (n = 3) (7%). Significant difference was not demonstrated
      statistically between BACTEC MGIT 960 and Lowenstein-Jensen medium in terms of
      mycobacterial recovery rate (p > 0.05). CONCLUSIONS: The present study showed
      82.6% smear negative pulmonary tuberculosis cases were still etiologically
      unexplained by culture. Therefore, there is a need to develop a scheme to
      determine the most cost-effective approaches for the diagnosis of smear negative
      pulmonary tuberculosis in the Ethiopian setting, such as improving the screening
      method patients with tuberculosis and other chronic pulmonary diseases, chest-x
      ray readings and interpretation, specimen collection and processing, smear
      microscopy, culture and applying laboratory quality control schemes in parallel.

PMID- 19743777
TI  - Investigation of antibacterial activities of Albizia gummifera and Ferula
      communis on Streptococcus pneumoniae and Streptoccus pyogenes.
AB  - BACKGROUND: Respiratory Tract infections continue to be a major cause of
      morbidity and mortality world wide. There is a failure to treat respiratory
      infections due to the emergence of antibiotic resistant strains among the most
      common respiratory pathogens. OBJECTIVES: To evaluate the in vitro antibacterial
      activities of two traditionally used plants: Albizia gummifera (Ambabesa-Muka,
      Oromifa, Sessa-Amharic.) and Ferula communis (Doge-Oromifa, Dog-Amharic) against
      clinical isolates of S. pyogenes and S. pneumoniae. METHODS: The study involving
      the antibacterial susceptibility test of traditionally used plant species against
      Gram-positive bacterial pathogens was conducted over a period of 5 months
      (January - August, 2004) at the Ethiopian Health, and Nutrition Research
      Institute. The in vitro antibacterial activities of 80% methanol crude extracts
      prepared from the seeds of Ablizia gummifera and, roots of Ferula communis as
      well as their respective hydro alcoholic solvent fractionates of both plant
      species were tested for inhibitory activity against the clinical isolates of six
      S. pneumonae and twenty two S. pyogenes using agar dilution method. RESULTS:
      Eighty percent ethanol solubilized fractions of both plants were found to have
      antibacterial effects to all assayed bacteria while aqueous solubilized fractions
      did not exhibit any effect. Minimum inhibitory concentration (MIC) of the 80%
      ethanol solubilized fractions was determined and the MIC of the fractions ranged
      from 500 mg/ ml to 1000 mg/ml for both plants showing the extracts may contain
      bioactive compounds of therapeutic interest. CONCLUSION: All extracts showed
      antibacterial activities against clinical isolates of S. pyogenes and S.
      pneumoniae. The extracts may contain compounds with potential therapeutic
      activity. Further purification and identification are needed to be tested using
      animal models.

PMID- 19743778
TI  - Pattern of upper gastrointestinal tumors at Tikur Anbessa Teaching Hospital in
      Addis Ababa, Ethiopia: a ten-year review.
AB  - BACKGROUND: Due to lack of public awareness and cancer surveillance, patients in
      developing countries usually present with advanced and terminal malignancies. The
      absence of early diagnostic facilities and standard chemotherapeutic and
      radiotherapy services in low-income countries further confound the problem in the
      care of such patients. Moreover, the prevalence of cancers (including upper GI
      malignancies) is unknown in Ethiopia due to lack of national cancer registry.
      OBJECTIVE: To assess the type and the pattern of upper GI tumors among the
      patients whose upper GI tract biopsies were seen at the Tikur Anbessa Hospital
      (TAH) during September 1, 1992 through August 31, 2002. METHODOLOGY: A ten-year
      retrospective analysis of upper gastrointestinal tract (UGIT) biopsy reports of
      adult patients was made at the Tikur Anbessa teaching Hospital. RESULTS: There
      were 608 UGIT biopsy specimens submitted to the pathology department of Addis
      Ababa University Medical Faculty, from different hospitals and clinics in the
      country for histological studies. There were 369 males (67.7%) and 239 (39.3%)
      females with a male to female ratio of 1.5:1. The mean age for males was 50 years
      while 48 years for females. Although most of biopsies were submitted from Addis
      Ababa and Shewa, esophageal squamous cell carcinoma and adenocarcinoma were
      apparently predominant among the patients from Arsi and Bale areas as compared to
      Addis Ababa and other regions. The mean duration of major presenting symptoms was
      4-6 months both for esophageal and gastric cancers. In this study, upper GI
      endoscopy had a 90% correlation with the histological diagnosis. CONCLUSION:
      Esophageal cancers were observed to be relatively common among the patients from
      Arsi and Bale zones while gastric cancers were apparently predominant among
      patients referred from Addis Ababa. Upper GI endoscopic diagnosis was also noted
      to correlate well with the histological diagnosis.

PMID- 19743779
TI  - Evaluation of Hanifin and Rajka atopic eczema diagnostic guidelines for reduced
      minor criteria.
AB  - BACKGROUND: Different atopic eczema diagnostic guidelines have been proposed for
      the diagnosis of atopic eczema. But the Hanifin and Rajka major and minor
      criteria seem to have got a better acceptance internationally. The aim of this
      study is to select those minor criteria which are most relevant to the Ethiopian
      situation, and eventually propose them to be used as a standard in Ethiopia.
      METHODS: Using the Hanifin and Rajka (HR) atopic eczema diagnostic guidelines as
      a gold standard, a total of 119 atopic eczema patients were selected from the
      diagnostic clinic of ALERT hospital Sensitivities to diagnose atopic eczema were
      calculated for six subgroups, formed by serially reducing increasing number of
      minor criteria from the gold standard RESULTS: When seven and twelve minor
      criteria are reduced from the Hanifin and Rajka atopic eczema diagnostic
      guidelines the sensitivities to detect an atopic eczema case were 96.64% and
      86.55% respectively. When further criteria were reduced the sensitivities dropped
      down significantly. CONCLUSIONS: Only nine minor criteria (itching while
      sweating, course influenced by environmental factors/ emotional stress, Dennie
      Morgan infraorbital folds, recurrent conjunctivitis, hand dermatitis, foot
      dermatitis, white demographismus, facial erythema and pityriasis alba) are the
      most relevant minor criteria for the diagnosis of atopic eczema in Ethiopia.
      Xerosis can be taken as one major criterion.

PMID- 19743780
TI  - Spleen length in childhood with ultrasound normal based on age at Tikur Anbessa
      Hospital.
AB  - BACKGROUND: Spleen is a hemopoetic organ which is capable of supporting elements
      of different systems. Determination of pathologic changes in size of spleen
      necessitates knowing the normal range of dimensions in healthy neonates, infant,
      and children. OBJECTIVE: The study was done with the purpose of estimating normal
      spleen measurement in pediatric subjects. METHODS: This is a cross-sectional
      prospective study conducted among children from birth up to 15 yrs at Black Lion
      and St. Paulos Hospital from May 2005 up to November 2005. RESULT: Among 152
      children 86 (56.6%) of the study subjects were males and the rest 66 (43.4%) were
      females. In addition 54 (35.5%) were above eight years and 98 (64.5%) were less
      than or equal to eight years. The average spleen size for children 0-3 and 3-6
      months, 10-12 and 12-14 years were 5.6 cm, 6 cm, 11.2 cm and 11.97 cm
      respectively. CONCLUSION: The length of the spleen and left kidney are equivalent
      at birth and grow with almost equal rate with the age of the subject. The ratio
      of the spleen-to-left kidney is almost one at all age groups, which can be
      helpful in case there is doubt of splenomegally.

PMID- 19743781
TI  - Incidence of normal pineal and chroids plexus calcification on brain CT
      (computerized tomography) at Tikur Anbessa Teaching Hospital Addis Ababa,
      Ethiopia.
AB  - OBJECTIVE: To determine the incidence of normal calcification of pineal gland and
      choroids plexus on Brain -CT (computerized Tomography) and to see its association
      with age and sex. METHOD: A cross-sectional descriptive study was conducted at
      Radiology Department, Tikur Anbessa Teaching Hospital, Addis Ababa, Ethiopia from
      May 2001 to August 2002. A total of 518 patients; 312 males and 206 females
      underwent brain-CT without pineal or choroids plexus pathology. RESULTS: The over
      all incidence of normal pineal gland calcification was 72.0 % and that of choroid
      plexus 43.3 %. The incidence of normal pineal gland and choroids plexus
      calcification were higher in males than in females by 13.1% and 6.0%
      respectively. The frequency of pineal gland and choroids plexus calcification
      showed a steady increase with age on both sex groups. CONCLUSION: The incidence
      of normal pineal gland calcification in this study is similar to most of the
      findings of other studies while the incidence of choroids plexus calcification
      was lower as compared the finding of other studies.

PMID- 19743782
TI  - Decentralized psychiatric nursing service in Ethiopia--a model for low income
      countries.
AB  - Mental health services in low income countries are inadequate. Health care
      delivery services in these countries are mainly focused on vector-borne diseases
      and HIV/AIDS. To make the situation worse, trained health workers are leaving
      developing countries for higher paying jobs elsewhere; this "brain drain" is
      robbing countries of their energetic and highly trained manpower. In response to
      this dire situation, Ethiopia started a psychiatric nursing training program
      where by nurses are trained and assigned to different parts of the country as
      mental health workers. Their activities range from prescribing psychiatric and
      anti epileptic drugs to counselling and teaching the local community about early
      identification and prevention of mental and behavioural disorders. While
      decentralization of mental services started twenty years ago and has played a
      major role in promoting mental health in the country, more needs to be done to
      retain existing staff and attract more mental health workers to the field. This
      paper examines the services provided by psychiatric nurses throughout the
      country. It attempts to evaluate strengths and weaknesses of the program and
      suggest recommendations which might be helpful for similar programs in low-income
      countries where highly trained mental health professionals are a luxury.

PMID- 19743783
TI  - Transurethral resection of the prostate (TURP)--in the treatment of benign
      prostatic hypertrophy (BPH) in Mekelle, Ethiopia.
AB  - OBJECTIVE: To study the efficacy and safety of TURP in the treatment of
      symptomatic benign prostatic hypertrophy (BPH) disease. PATIENTS AND METHODS:
      This was a retrospective record analysis of patients seen at the surgical
      referral clinic from Dec. 01, 2003 to Nov. 30, 2006 in Mekelle hospital with
      symptoms suggestive of bladder outflow obstruction caused by BPH. All patients
      included were carefully scrutinized and subjected to general medical evaluation
      including digital rectal examination (DRE) and abdominal ultrasonography. The
      volume, the size of the prostate and the symptoms of BPH were recorded and
      analyzed. The prostate volume not more than 80 cm3 with moderate to severe
      obstructive symptoms was selected for TURP offers. RESULTS: During the study
      there were 71 patients with symptomatic BPH disease among whom 65 cases underwent
      TURP in Mekelle hospital. In the latter group, ages ranged from 42-86 years with
      median age of 70 years (mean 66.8 years). Of the total patients seen for BPH
      disease, six patients had prostate volume greater than 80 cm3 determined by
      abdominal ultrasonography with DRE who underwent open surgical treatment. Four
      and two cases had retropubic and transvesical prostatectomies respectively
      accounting for 8.4%. Longer hospital stay and more resource implications were
      observed in this group. Of the 65 cases, in sixty (92.3%) patients, TURP alone
      was of fered. Three (4.6%) cases had both BPH and bladder stone diseases all
      treated by TURP and litholapaxy at one go. Of these patients two (3.0%) cases had
      urethral stricture with BPH treated by DVU (direct vision internal urethrotomy)
      and TURP. In fifty eight (89.2%) of the patients, the outcome after TURP was
      successful in relieving symptoms. The hospital stay after TURP offers ranged from
      2 up to 5 days, the median was 3 days and the mean 2.5 days. CONCLUSION: The
      present study has revealed that in 58 (89.2%) of the patients with BPH, TURP
      provided relief of symptoms and improvements in urine flow with minimum
      complications.

PMID- 19743784
TI  - Pattern of neural tube defects at Tikur Anbessa Hospital, Addis Ababa, Ethiopia.
AB  - BACKGROUND: Neural Tube Defect (NTD) is the most common of the central nervous
      system malformations. Although there is scarcity of information in Ethiopia, the
      burden of disease is high in low socioeconomic countries. OBJECTIVE: To assess
      the pattern and frequency of Neural Tube defects (NTDs). METHODS: Charts of a
      total of 115 children with neural tube defect (NTD) were reviewed retrospectively
      from JANUARY, 2001 to June 2005 in Ethio Swedish Children's Hospital. RESULTS:
      The most common defect seen was myelomeningocele (64.4%); followed by meningocele
      (18.3%) and encephalocele (13.0%). Associated anomalies like clubfoot undescended
      testis, different types of hernias, hydroceles etc. were noted in 28.7% of the
      patients. CONCLUSION: This study showed that the frequency distribution of the
      different neural tube defects in Tikur Anbessa hospital is not different from
      previous findings mentioned in the literature. However, overall frequency of
      neural tube defects could not be calculated from this study since the total live
      births in the study area during the study period were unknown. Hence, further
      prospective study is needed to substantiate these facts.

PMID- 19743785
TI  - Leishmaniasis (PKDL) as a case of immune reconstitution inflammatory syndrome
      (IRIS) in HIV-positive patient after initiation of anti-retroviral therapy (ART).
AB  - 25 years old HIV-positive farmer on Anti-retroviral therapy from North Ethiopia
      with PKDL occurring as IRIS is reported. He developed popular and nodular lesions
      on the face, chest and arms (Grade II severe PKDL) one month after anti
      retroviral therapy initiation, who had history of therapy for visceral
      leishmaniasis (VL) one year back. PKDL manifesting as IRIS after ART initiation
      in previously treated case for VL was among the few reported case in the world.
      The case is presented and discussed with the few available review literatures.

PMID- 19743786
TI  - Weill Marchesani syndrome with chronic angle closure glaucoma in Ethiopia: a case
      report.
AB  - Weill Marchesani syndrome (WMS) is a rare condition characterized by short
      stature, brachydactyly, joint stiffness, and characteristic eye abnormalities
      including microspherophakia, ectopia of the lens, severe myopia, and glaucoma. We
      report a typical case of WMS in an 18-year old female Ethiopian patient who
      presented with progressive visual loss from chronic angle closure glaucoma
      secondary to lens subluxation. Patients with WMS require early diagnosis in order
      to treat serious ocular and life-threatening systemic complications. To the best
      of our knowledge, only one case of the syndrome was previously reported in
      Africa.

PMID- 19743787
TI  - The choice of a margin of error in the calculation of an appropriate sample size
      in health research.

PMID- 19743788
TI  - Meeting the millennium development goals in health sector: as theme issue on EMA
      annual conference.

PMID- 19743789
TI  - Maternal mortality studies in Ethiopia--magnitude, causes and trends.
AB  - BACKGROUND: Reduction of maternal mortality is a global public health priority.
      Periodic maternal mortality studies are required to monitor changing trends. Both
      direct and indirect methods of maternal mortality measurement are used in
      different settings. OBJECTIVES: To study the geographic coverage, study base,
      type, maternal mortality ratio level and proportion of different causes of
      maternal deaths identified by maternal mortality studies conducted in Ethiopia.
      METHODS: Electronic databases search coupled with search in local journals of
      health as well as interview with relevant university departments for unpublished
      literatures on maternal mortality studies was conducted. Structured questionnaire
      was used to extract relevant data which was analyzed using SPSS 13 statistical
      package. RESULTS: Twelve maternal mortality studies were identified from 1980 to
      2008. Eight were hospital based and four community based studies. Only two were
      based on a national sample. Maternal mortality ratios ranged from 567 to 2600 per
      hundred thousand live births. Hospital studies had nearly double ratios compared
      to community studies. Maternal mortality ratios from hospitals outside Addis were
      nearly double or more compared to Addis hospital ratios. Abortion complications,
      ruptured uterus, puerperal sepsis, postpartum hemorrhage and preeclampsia/
      eclampsia were the five major causes of maternal mortality. The only study
      conducted since 2000 has shown a marked reduction in abortion related mortality;
      compared to findings of earlier studies. CONCLUSION: Only four of the country's
      nine regions were covered by the hospital studies. The large pastoralist
      community has not been adequately addressed by any of the studies. There is a
      need to conduct national health facility based studies to gather representative
      data on the proportion of different causes of maternal deaths and their
      predisposing factors. Inclusion of verbal autopsy techniques to demographic and
      health surveys and the decennial census can increase the power of these studies
      to define maternal mortality in more detail. In general, there is a paucity of
      information on maternal mortality.

PMID- 19743790
TI  - Screening and case detection for tuberculosis among people living with HIV in
      Addis Ababa, Ethiopia.
AB  - BACKGROUND: The spread of HIV epidemic in Africa has resulted in a fourfold
      increase in the number of tuberculosis cases. Screening for tuberculosis among
      people living with HIV would increase case detection. In Ethiopia, it is neither
      practiced well nor researched in depth. OBJECTIVE: To assess the proportion of
      Screening and Case Detection for Tuberculosis among People Living with HIV.
      MATERIALS AND METHODS: Between February 2008 and May 2008, a cross sectional
      facility-based survey was conducted by exit interview of 406 people living with
      HIV whether they have been asked by health providers for the presence of cough or
      unusual lump in their lymph node sites as recommended by National TB/HIV
      implementation guideline from HIV chronic care. RESULT: Based on our findings,
      89.7% of clients reported being screened for tuberculosis at least once during
      their follow-up visits. The case detection rate while screening was 15.6%. Male
      respondents were about two times more likely to be diagnosed for tuberculosis
      than females [AOR (95% CI) 2.18 (1.30-3.66)]. CONCLUSIONS: In general, there was
      high proportion of screening and case detection for tuberculosis among people
      living with HIV. The screening has to be well strengthened as many more active
      cases can be detected.

PMID- 19743791
TI  - Bacteriology of surgical site and catheter related urinary tract infections among
      patients admitted in Mekelle Hospital, Mekelle, Tigray, Ethiopia.
AB  - BACKGROUND: Nosocomial infections are widespread and are important contributors
      to morbidity and mortality. Prevalence studies are useful in revealing the
      prevalence of hospital-acquired infections. OBJECTIVES: To determine the
      bacterial pathogens associated with hospital acquired surgical site infection
      (SSI) and urinary tract infection (UTI) and assess their susceptibility patterns
      in patients admitted in Mekelle Hospital in Ethiopia. METHODS: From November 2005
      to April 2006 a prospective cross sectional study was conducted at Mekelle
      Hospital, Tigray region, North Ethiopia. The study population comprised of a
      total of 246 informed and consented adult patients hospitalized for surgical (n =
      212) and Gynecology and Obstetrics cases (n = 34). RESULTS: Of the 246 admitted
      patients, 68 (27.6%) developed nosocomial infections (SSI and/or nosocomial UTI)
      based on the clinical evaluations, and positive wound and urine culture results.
      Gram negative bacteria were predominantly isolated with a rate of 18/34 (53%) and
      34/41 (83%) from SSI and UTI respectively. Most of the isolates from UTI have
      high rates of resistance (> 80%) to the commonly used antibiotics such as
      ampicillin, amoxicillin, chloramphenicol, gentamicin, streptomycin, and
      trimethoprim-sulphamethoxazole; and in isolates from SSI to amoxicillin and
      trimethoprim-sulphamethoxazole. CONCLUSIONS: The results showed that the
      prevalence of HAIs (SSI and nosocomial UTI) in the Hospital is high when compared
      to previous Ethiopian and other studies despite the use of prophylactic
      antibiotics. The pathogens causing SSI and UT7 are often resistant to commonly
      used antimicrobials. The findings underscore the need for an infection control
      system and surveillance program in the hospital and to monitor antimicrobial
      resistance pattern for the use of prophylactic and therapeutic antibiotics.

PMID- 19743792
TI  - Prevalence of anemia among school children in Addis Ababa.
AB  - OBJECTIVES: The aim of the study is to determine the prevalence of anemia among
      school children and adolescents in Addis Ababa. STUDY SETTING: Three schools in
      Addis Ababa were selected. The schools are one primary school and two high
      schools. STUDY DESIGN: A cross sectional survey was undertaken in three schools
      in the month of May, 2003. STUDY POPULATION: All children in three schools who
      consented to participate in the study were included in the study. A calculated
      sample of 707 was taken. MEASUREMENTS: Sociodemographic data and health related
      information were collected using a pre-tested structured questionnaire.
      Anthropometry was taken in standard ways. Hemoglobin was measured using HaemoCue.
      DATA ANALYSIS: Data was entered into a computer using SPSS statistical package.
      Selected variables were taken to determine for their association with anemia
      using multiple logistic regression model. RESULTS: The mean age was 14.96 years.
      Females accounted for 52.8% of the subjects. Prevalence of stunting was 32.8%
      while underweight was 41.5%. The mean Hgb level was 15.4 gm/dl (SD 2.4). The
      prevalence rate of anemia was 5.83%. The highest rate was noted among children
      aged 8 years, though there was no consistent trend. Among the selected variables
      none were predictors of anemia. CONCLUSION: Anemia is not an uncommon problem
      among school children in Addis Ababa. Further study is required to determine
      factors affecting occurrence of anemia for planning an intervention program.

PMID- 19743793
TI  - In-patient surgical mortality in Tikur Anbessa Hospital: a five-year review.
AB  - BACKGROUND: To our knowledge neither hospital nor population-based data is
      available about mortality patterns in Ethiopia. OBJECTIVE: This review summarizes
      the patterns of deaths that occurred in hospital under the care of surgical team,
      during the 5-year period. PATIENTS AND METHODS: This is a hospital based
      retrospective cross sectional analysis of mortality among surgical patients
      admitted to Tikur Anbessa Specialized Teaching Hospital (TASTH), Department of
      Surgery, Addis Ababa, Ethiopia in the period between January 2002 and December
      2006. The monthly activity reports, death registry sheets and death certificate
      of deceased patients from all surgical wards were analyzed using computer based
      statistical software SPSS version 11.0. Difference in proportions were examined
      using Chi-square test with its conventional criterion for statistical
      significance (p < 0.05). RESULTS: The study reviews 694 deaths from 9991 surgical
      admissions, and 9860 procedures at TASTH over the 5-year period. There were 6.9%
      overall deaths among the admissions and 7.0% per procedure. The postoperative
      mortality rate was 4.5% (443/9860). The male-to-female ratio was 2.9:1. The mean
      age was 41 [Standard Deviation, 17.38] years. Four hundred fifty-two (15.7%)
      patients admitted on emergency basis and 242 (3.4%) of elective admissions died
      while in hospital surgical care (p < 0.0001). About 56% of deaths resulted from
      non-traumatic causes whilst 44% from traumatic causes. Similarly operative deaths
      were observed in 443 (63.8%) while nonoperative mortality in 252 (32.2%). Among
      patients with trauma, isolated head injury (59.2%) was major cause of death (p <
      0.0001), while, of the non-traumatic admissions, malignancy accounted for 164
      (42.1%) of the deaths, When specialties are compared, significant number, 234
      (34.4%) of the deaths belong to neurosurgery unit (p < 0.0001) followed by
      general surgery. CONCLUSION: In conclusion, more men died than women did, more
      patients admitted on emergency basis died than patients admitted on elective
      basis (p < 0.0001). Although, the overall mortality rate of 7% and postoperative
      death rate of 4.5% is acceptable, it could have been reduced significantly had
      there been appropriate setting to manage trauma cases. Trauma and Neurosurgical
      cares are yet to develop and need special attention.

PMID- 19743794
TI  - Pattern of acute abdomen and variables associated with adverse outcome in a rural
      primary hospital setting.
AB  - OBJECTIVE: To analyze the clinical presentation, causes, outcomes of surgical
      intervention (as measured by postoperative morbidity and mortality), and
      variables associated with adverse outcomes of patients with surgically important
      acute abdominal pain. DESIGN: A cross sectional hospital based longitudinal case
      series analysis. SETTING: Glen C Olsen Memorial Primary General Hospital.
      Butajira, Ethiopia. SUBJECT: All patients admitted and operated for acute
      abdominal pain over a period of two years. (Oct. 10, 2004 -Nov. 20, 2006) OUTCOME
      MEASURES: Being referred from other centers, duration of symptoms, types of
      symptoms and physical findings, relevant investigations, diagnosis and procedure
      done, hospital stay, mortality, morbidity, and variables associated with adverse
      out comes. RESULTS: A total of 143 patients were operated and of them 55.2% were
      referred from other health care facilities. Male to female ratio was 2.5:1 and
      mean age of presentation was 26.6 +/- 16.6 years. Patients presented after an
      average of 88.4 +/- 87.9 hours of symptom onset. Intestinal obstruction 50
      (34.9%), acute appendicitis 35 (24.5%), Intussusceptions 23 (16.1%) and bowel
      perforation 16 (11.2%) were the leading causes of admission. Clinical variables
      found to have statistical significant association (P < 0.05) with adverse
      outcomes were referred patients, those with abdominal distension, absolute
      constipation, deranged vital signs, abdominal mass, guarding, positive
      vaginal/rectal examination and/or leukocytosis. The average hospital stay was
      8.74 +/- 4.66 days and 28.7% of patients develop one or more of acute
      complications. Forty two (29.4%) patients presented with deranged vital signs
      from either septic or hypovolemic shock and of them 7 (4.9%) died with subsequent
      multiple organ failure. CONCLUSION: Patients who presented early and immediate
      corrective measures were instituted had better outcome while those seen late
      developed unfavorable out-come with significantly higher complications. Therefore
      early detection and treatment of acute abdomen is essential.

PMID- 19743795
TI  - Assessment of public health implication of malaria-geohelminth co-infection with
      an emphasis on hookworm-malaria anemia among suspected malaria patients in
      asendabo, southwest Ethiopia.
AB  - INTRODUCTION: Malaria and geo-helminth infections are causes of severe illness
      and poor economic growth. Overlapping distributions of both parasites lead to
      high rate of co-infection. OBJECTIVE: The study was designed to assess public
      health importance of Malaria-geo-helminth co-infection with an emphasis on anemia
      in Asendabo, south west Ethiopia. METHODS: A total of 370 suspected malaria cases
      were involved in the study. Each stool sample was analyzed using Kato-Katz
      techniques. Thick blood films were used for detection and quantization of malaria
      parasites. Hemoglobin was determined using Sysmex hematology analyzer. RESULT:
      61.6% individuals were positive for at least one intestinal helminth and/or
      protozoan infection. Hookworm was the most prevalent (38%) followed by Ascaris
      lumbricoides (19.2%) and Trichuris trichiura (10.3%). Furthermore, 32.4% of the
      study participants were positive for either of the two Plasmodium species; of
      which 64.3% were P. falciparum and the rest 35.7% were P. vivax. Based on WHO
      definition of anemia, 27.6% were anemic cases and both hookworm and malaria
      infections were significantly associated with anemia (P < 0.05). 20.8% of study
      participants were co-infected with malaria and any helminth. Hookworm and malaria
      positive individuals had low mean hemoglobin concentration than their respective
      negative counter parts and the difference was significant (P < 0.05).
      Furthermore, mean hemoglobin concentration was significantly lowered in malaria
      hookworm co-infected individuals than individuals infected with either hookworm
      or malaria infection alone (F = 69.39, P = 0.000). CONCLUSION: In general malaria
      hookworm co-infections worsen hemoglobin loss. And we recommend that individuals
      co-infected should receive prompt health care to control and prevent
      morbidity/mortality from anemia.

PMID- 19743796
TI  - Clinical outcome of children on HAART at police referral hospital, Addis Ababa,
      Ethiopia.
AB  - BACKGROUND: Access to antiretroviral therapy (ART) in resource poor countries,
      like Ethiopia has become a reality. Provision of free ART started in Ethiopia in
      2005. There are currently 134,586 children under 14 years living with HIV/AIDS in
      Ethiopia. While more than 1/2 of these children are expected to require ART, only
      2512 (< 4%) were receiving it as of November 2006. OBJECTIVE: To evaluate the
      efficacy and safety of ART in children in Ethiopia METHODS: Data on 50 children
      with AIDS and who were naive for ART and for whom HAART was given beginning April
      2005-December 2006 at Police force referral hospital, in Addis Ababa, Ethiopia
      was analyzed. RESULTS: 50 children, age < 13 years with a mean age of 5.8 years
      +/- 3.5 years, were given HAART for a median duration of 15.2 months. At
      enrollment, the mean CD4+ T cells percentage of 25 children was 9.5 percent +/-
      5.8 percent. The mean percentage of CD4+ T cells of these 25 patients rose from
      9.5 percent at base line to 18.7 percent +/- 9.8 percent at 6 months (P < 0.001).
      The mean weight gain at 6 months was 2.94 kg (95% CI, 2.31 to 3.57). For the age
      group < 5 years, the mean increase in Z-score for weight for age was 1.39 (95%
      CI, 0.48 to 2.295) at 6 months. There was a significant difference in the
      admission rates of patients on HAART, one year prior to and one year after ART
      initiation, with a mean of 1.08 and 0.27 admissions per person per year
      respectively (P < 0.001). Of the 50 children 3 (6 percent) died during follow-up.
      Treatment limiting toxic effects occurred in one of the 50 children on HAART (2
      percent). CONCLUSIONS: This data documents the efficacy and safety of ART in
      children even in resource poor countries. The outcomes are comparable to those in
      developed and some developing countries. This calls for more effort to make ART
      widely accessible to all children who need it.

PMID- 19743797
TI  - Splenectomy: experience from Tikur Anbessa Hospital, Addis Ababa 1988-2007.
AB  - OBJECTIVE: To bring some light on the question of the rationale for splenectomy
      in Ethiopian patients. SUBJECTS AND METHOD: Consecutive patients from the last 19
      years treated at Tikur Anbessa Hospital were collected and classified mainly on
      etiological ground for a discussion on the indication and outcome. RESULTS:
      During 1981-1999 EC corresponding to 1988-2007 GC, 155 patients had splenectomy
      in Department of Surgery, Tikur Anbessa Hospital Addis Ababa; splenectomies were
      common in young adult patients. The median age was 20-24 years and there was a
      slight preponderance of males. The most common reasons for splenectomy were
      hematological disorders and congestive splenomegally with esophageal varices.
      Splenectomy after trauma and perioperative removal of the spleen were few in
      number. Other reasons for splenectomy, such as abscess, cysts and haemangioma
      were rare. Five cases from the Pediatric age group were all from the first years
      of the study. CONCLUSION: the described series of splenectomies is high in
      number. That should be expected in countries like Ethiopia, where tropical
      conditions like schistosomiasis and malaria have a high prevalence causing
      splenomegally and where the removal of the spleen is often in combination with
      portoazygos disconnection. Splenectomies for other indications are similar in
      number in western countries. The functions of the spleen are very important and
      to some extent vital and splenectomy should not be undertaken unless there is a
      rational ground.

PMID- 19743798
TI  - Cesarean scar endometriosis--a case report.
AB  - Scar endometriosis is a rare event which usually develops after pelvic operations
      involving the uterus and fallopian tubes. Its diagnosis can sometimes be
      difficult and may be confused with various other surgical conditions. We present
      here a case of abdominal wall scar endometriosis in a woman who has undergone
      cesarean delivery four years prior to her current presentation. The epidemiology,
      pathogenesis, clinical features, diagnosis, treatment and methods of prevention
      of this condition will be discussed in brief. This is an interesting case of
      surgical scar endometriosis and to the best of our knowledge this is the first
      case report in Ethiopia.

PMID- 19743799
TI  - Popliteal Pterygium Syndrome--a case report.
AB  - We report a case of Popliteal Pterygium Syndrome (PPS) in a neonate born at term
      to a primigravid mother. There was no family history of PPS. The neonate was
      treated successfully at Yekatit 12 hospital reconstructive surgery unit, and we
      discuss the management and the outcome. Literature review is made.

PMID- 19743800
TI  - Angiolymphoid hyperplasia with eosinophilia in a 29 years old Ethiopian patient,
      diagnosed using clinicopathologic correlation.
AB  - We report a case of Angiolymphoid hyperplasia with eosinophilia in a 29 years old
      female Ethiopian patient. This case was diagnosed by establishing a
      clinicopathologic correlation. This is the first case of its kind ever reported
      in Ethiopia. The clinical features, dermatohistopathological findings, and
      treatment options are discussed with review of literature.

PMID- 19743801
TI  - Natural polyphenols as direct trapping agents of lipid peroxidation-derived
      acrolein and 4-hydroxy-trans-2-nonenal.
AB  - Acrolein (ACR) and 4-hydroxy-trans-2-nonenal (HNE) are two cytotoxic lipid
      derived alpha,beta-unsaturated aldehydes which have been implicated as causative
      agents in the development of carbonyl stress-associated pathologies. In this
      study, 21 natural polyphenols were screened to identify effective scavenging
      agents of ACR and/or HNE in simulated physiological conditions. It was found that
      flavan-3-ols, theaflavins, cyanomaclurin, and dihydrochalcones effectively
      trapped ACR and HNE by working as sacrificial nucleophiles. The most effective
      one was phloretin, which quenched up to 99.6% ACR in 90 min and 90.1% HNE in 24
      h. Subsequent LC-MS/MS analysis showed that these effective polyphenols formed
      adducts with ACR and HNE. A major adduct formed from phloretin and ACR was
      purified, and its structure was characterized by LC-MS and NMR spectroscopy as
      diACR-conjugated phloretin. The chemical nature of interactions between ACR and
      polyphenols was proposed as the Michael addition reaction of phloretin to the C
      horizontal lineC double bond of ACR, followed by the formation of hemiacetal
      between the hydroxyl group in the A ring of phloretin and the C horizontal lineO
      carbonyl group in ACR, thus yielding more stable products. Findings of the
      present study highlighted certain classes of polyphenols as promising
      sequestering agents of alpha,beta-unsaturated aldehydes to inhibit or restrain
      carbonyl stress-associated diseases.

PMID- 19743802
TI  - Catechol type polyphenol is a potential modifier of protein sulfhydryls:
      development and application of a new probe for understanding the dietary
      polyphenol actions.
AB  - The oxidation of dietary polyphenols with a catechol structure leads to the
      formation of an o-quinone structure, which rapidly reacts with sulfhydryls such
      as glutathione and protein cysteine residues. This modification may be important
      for understanding the redox regulation of cell functions by polyphenols. In this
      study, to investigate the catechol modification of protein sulfhydryls, we used
      3,4-dihydroxyphenyl acetic acid (DPA) as a model catechol compound and developed
      a new probe to directly detect protein modification by catechol type polyphenols
      using a biotinylated DPA (Bio-DPA). The oxidation-dependent electrophilic
      reactivity of DPA with peptide sulfhydryls was confirmed by both mass
      spectrometry and nuclear magnetic resonance spectroscopy. When RL34 cells were
      treated with Bio-DPA, the significant incorporation of Bio-DPA into a 40 kDa
      protein was observed by Western blot analysis. The band was identified by mass
      spectrometry as the cytoskeletal protein, beta-actin. This identification was
      confirmed by the pull-down assay with anti-beta-actin antibody. To examine the
      reactivity of the catechol type polyphenols, such as flavonoids, to endogenous
      beta-actin, RL34 cells were coexposed to Bio-DPA and the flavonoids quercetin, (
      )-epicatechin, and (-)-epicatechin gallate. Upon exposure of the cells to Bio-DPA
      in the presence of the flavonoids, we observed a significant decrease in the DPA
      modified beta-actin. These results indicate that beta-actin is one of the major
      targets of protein modification by catechol type polyphenols and that Bio-DPA is
      an useful probe for understanding the redox regulation by dietary polyphenols.
      Furthermore, Keap1, a scaffold protein to the actin cytoskeleton controlling
      cytoprotective enzyme genes, was also identified as another plausible target of
      the catechol type polyphenols by oxidative modification of the intracellular
      sulfhydryls. These results provide an alternative approach to understand that
      catechol type polyphenol is a potential modifier of redox-dependent cellular
      events through sulfhydryl modification.

PMID- 19743803
TI  - Enantioselective chemoenzymatic synthesis of trans-aziridines.
AB  - A straightforward, five-step procedure for the synthesis of enantiomerically pure
      2,3-disubstituted trans-aziridines has been developed starting from commercially
      available aldehydes. Hydroxynitrile lyase-mediated cyanohydrin formation provided
      cyanohydrins in excellent enantioselectivities and good yields. Subsequent
      formation of diastereomerically pure anti-amino alcohols via a one-pot Grignard
      addition-reduction sequence, Cu(II)-catalyzed diazotransfer, and
      triphenylphosphine-mediated reductive cyclization provided the corresponding
      trans-aziridines in good yields and excellent diastereoselectivities.

PMID- 19743804
TI  - Exploring the binding ability of phenanthroline-based polyammonium receptors for
      anions: hints for design of selective chemosensors for nucleotides.
AB  - The synthesis of receptor 2,6,10,14,18-pentaaza[20]-21,34-phenanthrolinophane
      (L1), containing a pentaamine chain linking the 2,9 positions of a phenanthroline
      unit, is reported. The protonation features of L1 and of receptor 2,6,10,14,18,22
      hexaaza[23]-24,37-phenanthrolinophane (L2) have been studied by means of
      potentiometric, (1)H NMR, and spectrofluorimetric measurements; this study points
      out that the fluorescent emission of both receptors depends on the protonation
      state of the polyamine chain. In fact, the receptors are emissive only at neutral
      or acidic pH values, where all the aliphatic amine groups are protonated.
      Potentiometric titrations show that L2 is able to bind selectively ATP over TTP,
      CTP, and GTP. This selectivity is lost in the case of L1. (1)H and (31)P NMR
      measurements and molecular mechanics calculations show that the phosphate chains
      of nucleotides give strong electrostatic and hydrogen-bonding interactions with
      the ammonium groups of the protonated receptors, while the nucleobases interact
      either via pi-stacking with phenanthroline or via hydrogen bonding with the
      ammonium groups. Of note, MM calculations suggest that all nucleotides interact
      in an inclusive fashion. In fact, in all adducts the phosphate chain is enclosed
      within the receptor cavities. This structural feature is confirmed by the crystal
      structure of the [(H(6)L2)(2)(TTP)(2)(H(2)O)(2)](4+) adduct. Fluorescence
      emission measurements at different pH values show that L2 is also able to
      ratiometrically sense ATP in a narrow pH range, thanks to emission quenching due
      to a photoinduced electron transfer (PET) process from an amine group of the
      receptor to the excited phenanthroline.

PMID- 19743805
TI  - Investigations of the optical spectroscopy of atomic sodium isolated in solid
      argon and krypton: experiments and simulations.
AB  - The absorption spectra of thin film samples, formed by the codeposition of sodium
      vapor with the rare gases have long been known to consist of complex structures
      in the region of the atomic sodium "yellow-doublet" lines. The photophysical
      characteristics of the associated luminescence (excitation/emission) spectra,
      indicate strong interaction between the excited P state Na atom and the rare
      gases (Ar, Kr, and Xe) used as host solids. This system is reinvestigated with
      new experimental spectroscopic results and molecular dynamics (MD) calculations.
      The so-called "violet" site in Ar and Kr has been produced by laser excitation of
      thermally deposited samples. The simulation of the "spray-on" deposition of thin
      films enables identification of tetravacancy (tv) sites of isolation for ground
      state atomic sodium in Ar while in Kr this site is found in addition to single
      vacancy (sv) occupancy. Various cubic symmetry sites were taken into account to
      simulate absorption and emission spectra using accurate interaction potentials
      for the Na.RG diatomics. The well-known 3-fold splitting in absorption,
      attributed to the Jahn-Teller effect, was very well reproduced but the simulated
      spectra for all the sites considered are located in the low energy region of the
      experimental bands. The evolution of the excited state Na atom is followed
      revealing the nature and symmetry of the sites that are transiently occupied.
      Consistent with the large Stokes shift observed experimentally, there is an
      extensive rearrangement of the lattice in the excited state with respect to the
      ground state. Combining all the experimental and theoretical information, an
      assignment of experimental violet, blue, and red absorption features is
      established involving single vacancy, tetravacancy, and hexavacancy sites,
      respectively, in Ar and Kr.

PMID- 19743806
TI  - Interpreting the physical background of empirical solvent polarity via
      photodetachment spectroscopy of microsolvated aromatic ketyl anions.
AB  - The physical background of empirical solvent polarity is explored in regard to
      trends in solute-solvent intermolecular potential energy functions. Aromatic
      ketyl anions, benzophenone, and 9-fluorenone radical anions, are chosen for a
      model solute molecule showing solvatochromic behavior similar to betaine-30 dye,
      which provides the most established solvent polarity scale, E(T)(30). Common
      features among the ketyl anions and betaine-30 were examined with quantum
      chemical calculations for the electronic states and solvation structure. Vertical
      photodetachment and photoabsorption energies were determined for the ketyl anions
      microsolvated with a single solvent molecule by measuring photoelectron spectra
      as well as photodetachment excitation spectra for several aprotic and protic
      solvents. The spectroscopic data were analyzed through quantum chemical
      calculations based on density functional theory, and their relationship with the
      characteristics of intermolecular potential energies was considered. As a result,
      the typical solvent polarity parameter can be interpreted to reflect essentially
      the gradient of a potential energy function (namely, the strength of force)
      between a negative charge and the solvent molecules in the attractive region. A
      large polarity for protic solvents is attributed to an effective interaction of a
      proton-like hydrogen atom with the negative charge in a short-range.

PMID- 19743807
TI  - Solution-processable gradient red-emitting pi-conjugated dendrimers based on
      benzothiadiazole as core: synthesis, characterization, and device performances.
AB  - A family of gradient pi-conjugated dendrimers, in which the 5,5,10,10,15,15
      hexahexyltruxene unit is employed as the node, oligo(thienylethynylene)s (OTEs)
      are employed as light-harvesting branching units, and a 4,7-diaryl-2,1,3
      benzothiadiazole is employed as the core, have been developed through the
      Sonogashira reaction in good yields. All dendrimers were fully characterized by
      (1)H and (13)C NMR, elemental analysis, and MALDI-TOF MS. Investigation of their
      steady-state and time-resolved photophysical properties revealed that the
      gradient dendritic scaffold resulted in efficient energy transfer and strong red
      emission. On the basis of the good solubility and excellent film forming
      properties, single-layer red-emitting diodes using these dendrimers as the active
      materials were fabricated by a simple solution spin-coating process. The moderate
      device performance was achieved; for example, the maximum luminance of 1290
      cd/m(2) with a maximum luminescence efficiency of 1.07 cd/A was performed from
      BTDyn.

PMID- 19743808
TI  - Femtogram detection and quantitation of residues using laser ionization
      orthogonal time-of-flight mass spectrometry.
AB  - A newly developed high irradiance laser ionization orthogonal time-of-flight mass
      spectrometer (LI-O-TOFMS) was employed for the elemental analysis of residues,
      which were prepared by evaporating mixed salt solutions. The residues were first
      characterized in terms of shape and elemental distribution. In TOFMS detection,
      all of the metal elements in the residue can be observed in the spectra. Relative
      sensitivity coefficients for different elements were within 1 order of magnitude,
      which meets semiquantitative analysis criteria. By calculating the individual
      masses from the ablated area due to a single laser shot, the absolute detection
      limit reached 7 x 10(-15) g for most metal elements. The results indicate that LI
      O-TOFMS is capable of performing ultratrace elemental qualification and
      quantification, with an absolute limit of detection and an absolute limit of
      quantitation at the femtogram level.

PMID- 19743809
TI  - Bioactive guanidine alkaloids from two Caribbean marine sponges.
AB  - Seven new guanidine alkaloids (1-7) together with the known batzelladines A, F,
      H, and L, ptilomycalin A, and fromiamycalin were isolated from the Caribbean
      marine sponges Monanchora arbuscula and Clathria calla. Molecular structures were
      assigned on the basis of detailed analysis of 1D and 2D NMR spectra and mass
      spectrometry data, and bioactivities of the alkaloids were evaluated against
      human cancer cell lines and malaria protozoa.

PMID- 19743810
TI  - Isolation and structural elucidation of euryjanicins B-D, proline-containing
      cycloheptapeptides from the Caribbean marine sponge Prosuberites laughlini.
AB  - Three new cyclic peptides, euryjanicins B (2), C (3), and D (4), have been
      isolated from the Puerto Rican marine sponge Prosuberites laughlini, and the
      structures were elucidated by chemical degradation, ESIMS/MS, and extensive 2D
      NMR methods. When tested against the National Cancer Institute 60 tumor cell line
      panel, all of the purified isolates displayed weak cytotoxicity.

PMID- 19743811
TI  - Complex superstructures of Mo2P4O15.
AB  - We report structural studies on Mo(2)P(4)O(15) over the temperature range 16-731
      K, which show that it is considerably more complex than revealed by earlier work.
      Its low-temperature structure has lattice parameters a = 24.1134(6) A, b =
      19.5324(5) A, c = 25.0854(6) A, beta = 100.015(1) degrees, and V = 11635.0(5)
      A(3) at 120 K, containing 441 unique atoms in space group Pn, a remarkably high
      number for a material with such a simple composition. Mo(2)P(4)O(15) undergoes a
      structural phase transition at approximately 520 K to a high-temperature phase in
      space group P1, with lattice parameters a = 17.947(3) A, b = 19.864(3) A, c =
      21.899(3) A, alpha = 72.421(3) degrees, beta = 78.174(4) degrees, gamma =
      68.315(4) degrees, and V = 6877.2(19) A(3) at 573 K. The high-temperature
      structure, with 253 unique atoms, retains much of the low-temperature complexity.

PMID- 19743812
TI  - Moluccensins A-G, phragmalins with a conjugated C-30 carbonyl group from a
      Krishna mangrove, Xylocarpus moluccensis.
AB  - Seven new phragmalins with a C-30 carbonyl moiety, named moluccensins A-G (1-7),
      among which moluccensins A-F, possessing a Delta(8,14) double bond, and
      moluccensin G (7), containing conjugated Delta(8,9) and Delta(14,15) double
      bonds, were isolated from the seeds of an Indian mangrove, Xylocarpus
      moluccensis. The structures of these compounds were established on the basis of
      single-crystal X-ray diffraction analysis and spectroscopic data. This is the
      first report of phragmalins with a conjugated C-30 carbonyl group.

PMID- 19743813
TI  - Compensation for systematic cross-contribution improves normalization of mass
      spectrometry based metabolomics data.
AB  - Most mass spectrometry based metabolomics studies are semiquantitative and depend
      on efficient normalization techniques to suppress systematic error. A common
      approach is to include isotope-labeled internal standards (ISs) and then express
      the estimated metabolite abundances relative to the IS. Because of problems such
      as insufficient chromatographic resolution, however, the analytes may directly
      influence estimates of the IS, a phenomenon known as cross-contribution (CC).
      Normalization using ISs that suffer from CC effects will cause significant loss
      of information if the interfering analytes are associated with the studied
      factors. We present a novel normalization algorithm, which compensates for
      systematic CC effects that can be traced back to a linear association with the
      experimental design. The proposed method was found to be superior at purifying
      the signal of interest compared to current normalization methods when applied to
      two biological data sets and a multicomponent dilution mixture. Our method is
      applicable to data from randomized and designed experiments that use ISs to
      monitor the systematic error.

PMID- 19743814
TI  - Design and synthesis of a stable supramolecular trigonal prism formed by the self
      assembly of a linear tetrakis(Zn2+-cyclen) complex and trianionic trithiocyanuric
      acid in aqueous solution and its complexation with DNA (cyclen = 1,4,7,10
      tetraazacyclododecane).
AB  - A new supramolecular complex, {(Zn(4)L(4))(3)-(TCA(3-))(4)}(12+), was designed
      and synthesized by the 3:4 self-assembly of a linear tetrakis(Zn(2+)-cyclen)
      complex (Zn(4)L(4))(8+) and trianionic trithiocyanurate (TCA(3-)) in aqueous
      solution (cyclen = 1,4,7,10-tetraazacyclododecane). The {(Zn(4)L(4))(3)-(TCA(3
      ))(4)}(12+) complex, which should have a trigonal prism configuration, was found
      to be very stable in aqueous solution at neutral pH and 25 degrees C, as
      evidenced by (1)H NMR titration, potentiometric pH and UV titrations, and MS
      measurements. The complex does not dissociate into the starting building blocks
      in the presence of Zn(2+)-binding anions such as phosphates and double-stranded
      DNA. The results of the competitive binding assays with ethidium bromide and calf
      thymus DNA, thermal melting experiments, gel mobility shift assays, and dynamic
      light-scattering data strongly indicated that the trigonal prism functions as a
      polycationic template to induce the aggregation of double-stranded DNA.

PMID- 19743815
TI  - Stretched extracellular matrix proteins turn fouling and are functionally rescued
      by the chaperones albumin and casein.
AB  - While evidence is mounting that cells exploit protein unfolding for
      mechanochemical signal conversion (mechanotransduction), what mechanisms are in
      place to deal with the unwanted consequences of exposing hydrophobic residues
      upon force-induced protein unfolding? Here, we show that mechanical chaperones
      exist that can transiently bind to hydrophobic residues that are freshly exposed
      by mechanical force. The stretch-upregulated binding of albumin or casein to
      fibronectin fibers is reversible and does not inhibit fiber contraction once the
      tension is released.

PMID- 19743816
TI  - Efficient synthesis and evaluation of quorum-sensing modulators using small
      molecule macroarrays.
AB  - A method for the synthesis of small molecule macroarrays of N-acylated L
      homoserine lactones (AHLs) is reported. A focused library of AHLs was
      constructed, and the macroarray platform was found to be compatible with both
      solution and agar-overlay assays using quorum-sensing (QS) reporter strains.
      Several QS antagonists were discovered and serve to showcase the macroarray as a
      straightforward technique for QS research.

PMID- 19743817
TI  - Synthesis of cyclic hydroxamic acids through -NOH insertion of ketones.
AB  - Treatment of cyclobutanone or cyclopentanone with N-hydroxybenzenesulfonamide
      under basic conditions yields the ring-expanded cyclic hydroxamic acid in 18-69%
      yield. Reactions of substituted cyclobutanones give ring expanded products where
      the -NOH group regio- and stereoselectively inserts to the more substituted
      position. This expansion likely proceeds through a mechanism that includes
      addition of the N-anion of N-hydroxybenzenesulfonamide to the ketone and a C
      nitroso intermediate that rearranges to the final product.

PMID- 19743818
TI  - Chemoenzymatic access to versatile epoxyquinol synthons.
AB  - The enantiomerically pure and readily available metabolites 10-12 have been
      converted over four simple steps into the epoxyquinol derivatives 22-24,
      respectively. Compounds 23 and 24 or their immediate precursors have been
      exploited in efficient total syntheses of (-)-bromoxone (ent-1), (-)-epiepoformin
      (ent-2), (-)-harveynone (4), (+)-panepophenanthrin (6), and (+)-hexacyclinol (9).

PMID- 19743820
TI  - The monoadducts of sulfenyl chorides and conjugated diolefins.

PMID- 19743819
TI  - Asymmetric copper(I)-catalyzed Henry reaction with an aminoindanol-derived
      bisoxazolidine ligand.
AB  - Bisoxazolidine 1 is an effective ligand in the Me2Zn-promoted and the Cu(I)
      catalyzed Henry reaction. While a wide range of nitroaldol products are obtained
      in high yields and ee's in both cases, the replacement of dimethylzinc with
      copper(I) acetate results in a complete reversal of the sense of asymmetric
      induction. The Cu(I)-catalyzed enantioselective addition of nitromethane to
      methyl 4-oxobutanoate followed by hydrogenation and spontaneous lactamization
      gives (S)-5-hydroxypiperidin-2-one in 72% overall yield and 98% ee which compares
      favorably with previously reported methods.

PMID- 19743821
TI  - Molecular weight determination of block copolymers by pulsed gradient spin echo
      NMR.
AB  - Matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) mass
      spectrometry (MS) is the technique of choice to achieve molecular weight data for
      synthetic polymers. Because the success of a MALDI-MS analysis critically depends
      on a proper matrix and cation selection, which in turn relates closely to the
      polymer chemical nature and size, prior estimation of the polymer size range
      strongly helps in rationalizing MALDI sample preparation. We recently showed how
      pulsed gradient spin echo (PGSE) nuclear magnetic resonance could be used as an
      advantageous alternative to size exclusion chromatography, to rationalize MALDI
      sample preparation and confidently interpret MALDI mass spectra for homopolymers.
      Our aim here is to extend this methodology to the demanding case of amphiphilic
      block copolymers, for which obtaining prior estimates on the Mw values appears as
      an even more stringent prerequisite. Specifically, by studying poly(ethylene
      oxide) polystyrene block copolymers of distinct molecular weights and relative
      block weight fractions, we show how PGSE data can be used to derive the block Mw
      values. In contrast to homopolymers, such determination requires not only
      properly recorded calibration curves for each of the polymers constituting the
      block copolymers but also an appropriate hydrodynamic model to correctly
      interpret the diffusion data.

PMID- 19743822
TI  - Combined low temperature rapid scan and 1H NMR mechanistic study of the
      protonation and subsequent benzene elimination from a (diimine)platinum(II)
      diphenyl complex relevant to arene C-H activation.
AB  - A detailed kinetic study of the protonation and subsequent benzene elimination
      reactions of a (diimine)Pt(II) diphenyl complex (denoted as (N-N)PtPh(2)) has
      been undertaken in dichloromethane solution with and without acetonitrile as a
      cosolvent. Spectroscopic monitoring of the reactions by UV-vis stopped-flow and
      NMR techniques over the temperature range -80 to +27 degrees C allowed the
      assessment of the effects of acid concentration, coordinating solvent (MeCN)
      concentration, temperature, and pressure. Protonation of (N-N)PtPh(2) with HBF(4)
      x Et(2)O in CH(2)Cl(2)/MeCN occurs with a kinetic preference for protonation at
      the metal, rather than at a phenyl ligand, and rapidly produces (N
      N)PtPh(2)H(NCMe)(+) (DeltaH(double dagger) = 29 +/- 1 kJ mol(-1), DeltaS(double
      dagger) = -47 +/- 4 J K(-1) mol(-1)). At higher temperatures, (N
      N)PtPh(2)H(NCMe)(+) eliminates benzene to furnish (N-N)PtPh(NCMe)(+). This
      reaction proceeds by rate-limiting MeCN dissociation (DeltaH(double dagger) = 88
      +/- 2 kJ mol(-1), DeltaS(double dagger) = +62 +/- 6 J K(-1) mol(-1),
      DeltaV(double dagger) = +16 +/- 2 cm(3) mol(-1)). Protonation of (N-N)PtPh(2) in
      dichloromethane in the absence of MeCN cleanly produces the Pt(II) pi-benzene
      complex (N-N)PtPh(eta(2)-C(6)H(6))(+) at low temperatures. Addition of MeCN to a
      solution of the pi-benzene complex causes an associative substitution of benzene
      by acetonitrile, the kinetics of which were monitored by (1)H NMR (DeltaH(double
      dagger) = 39 +/- 2 kJ mol(-1), DeltaS(double dagger) = -126 +/- 11 J K(-1) mol(
      1)). When the stronger triflic acid is employed in dichloromethane/acetonitrile,
      a second protonation-induced reaction also occurs. Thus, (N-N)PtPh(NCMe)(+)
      produces (N-N)Pt(NCMe)(2)(2+) and benzene with no detectable intermediates
      (DeltaH(double dagger) = 69 +/- 1 kJ mol(-1), DeltaS(double dagger) = -43 +/- 3 J
      K(-1) mol(-1)). The mechanisms for all steps are discussed in view of the
      accumulated data. Interestingly, the data allow a reinterpretation of a previous
      report on proton exchange between the phenyl and benzene ligands in (N
      N)PtPh(eta(2)-C(6)H(6))(+). It appears that the exchange occurs by a direct sigma
      bond metathesis pathway, rather than by the oxidative cleavage/reductive coupling
      sequence that was proposed.

PMID- 19743823
TI  - Electronic structure of the A(8)Tr(11) (A = K, Rb, Cs; Tr = Ga, In, Tl) Zintl
      phases: possible chemical reasons behind their activated versus non activated
      conductivity.
AB  - The electronic structure of the A(8)Tr(11) (A = K, Cs; Tr = Ga, In, Tl) Zintl
      phases has been studied by means of first-principles density functional theory
      (DFT) calculations. It is shown that the hypoelectronic Tr(11) cluster in these
      phases must be considered as Tr(11)(8-) even if it would require just a 7- charge
      to maximize its bonding, filling all its bonding and nonbonding levels. Our
      calculations show that the lowest empty orbital of the isolated Tr(11)(7-)
      clusters is an a(1)-type orbital. However, a degenerate e-type set of orbitals is
      higher but quite close in the case of the Ga(11)(7-) clusters. Thus, for the
      isolated Tr(11)(8-) clusters, the extra electron occupies always an a(1)-type
      antibonding orbital that contains, however, some Tr-Tr bonding component thus
      leading to a weak global antibonding character. In the solid, cluster-alkali
      metal bonding interactions occur and spread the cluster levels into bands, but
      the extra electron still fills the a(1)-type cluster level for most of the
      A(8)Tr(11) phases. The cluster-alkali-metal interactions have a minor role in
      stabilizing this orbital but they provide the necessary delocalization to lead to
      the metallic character of these phases. In contrast, the e-type antibonding
      levels of the Ga(11)(7-) isolated cluster are those which become filled by the
      extra electron in the Cs(8)Ga(11) solid. This phase should be metallic, but
      occupation of this degenerate pair of cluster levels would lead to a structural
      instability that may be avoided by reducing the interactions of the alkali-metal
      atoms with the cluster levels. In that way the occupation appropriate for the
      isolated cluster is restored (i.e., one electron fills the a(1) cluster orbital),
      but the extra electron now remains localized on the cluster, thus leading to the
      unexpected activated conductivity observed for the Cs(8)Ga(11) phase.

PMID- 19743824
TI  - Syntheses, structures, and magnetic properties of nickel-doped lepidocrocite
      titanates.
AB  - Ni-doped titanate Cs(x)Ti(2-x/2)Ni(x/2)O(4) and its protonic derivative H(x)Ti(2
      x/2)Ni(x/2)O(4) x xH(2)O (x = 0.7) were synthesized and characterized by means of
      synchrotron X-ray diffraction, Raman scattering, X-ray photoelectron spectroscopy
      (XPS), and magnetic measurements. Cs(x)Ti(2-x/2)Ni(x/2)O(4) crystallizes in an
      orthorhombic structure (space group Immm), consisting of infinite two-dimensional
      (2D) host layers of the lepidocrocite (gamma-FeOOH) type. The substitution of Ni
      atoms for Ti in the 2D octahedral layers results in negative charges that are
      compensated by interlayer Cs(+) ions. Raman scattering and XPS indicate that
      local structural perturbations are induced upon exchange of interlayer Cs ions
      with protons H(3)O(+). Magnetic measurements reveal typical paramagnetism induced
      by Ni substitution; the effective paramagnetic moment mu(eff) = 1.57(1) mu(B) and
      Curie-Weiss temperature -2.51(1) K are obtained for H(x)Ti(2-x/2)Ni(x/2)O(4) x
      xH(2)O. Ni- and Mg-codoped titanates Cs(x)Ti(2-x/2)(Ni(y)Mg(1-y))(x/2)O(4) (x =
      0.7, 0 < or = y < or = 1) were also reported. The crystal structure, interlayer
      chemistry, and magnetic properties of the titanates depend on the Ni substitution
      levels, indicating opportunities for tuning of the properties by controlling the
      nature and level of lattice substitutions.

PMID- 19743825
TI  - An efficient synthesis of chiral diamines with rigid backbones: application in
      enantioselective Michael addition of malonates to nitroalkenes.
AB  - A new and efficient route for synthesis of enantiomerically pure biisoindoline
      and its isomer based on the diaza-Cope rearrangement reaction with chiral 1,2
      bis(2-hydroxylphenyl)-1,2-diaminoethane as starting material has been developed.
      The newly prepared biisoindoline was employed as a chiral ligand in the Ni(II)
      catalyzed enantioselective Michael addition of malonates to conjugated
      nitroalkenes, and good to excellent enantioselectivities were obtained.

PMID- 19743826
TI  - Influence of the interfacial peptide organization on the catalysis of hydrogen
      evolution.
AB  - The hydrogen evolution reaction is catalyzed by peptides and proteins adsorbed on
      electrode materials with high overpotentials for this reaction, such as mercury.
      The catalytic response characteristics are known to be very sensitive to the
      composition and structure of the investigated biomolecule, opening the way to the
      implementation of a label-free, reagentless electroanalytical method in protein
      analysis. Herein, it is shown using the model peptide Cys-Ala-Ala-Ala-Ala-Ala
      that the interfacial organization significantly influences the catalytic
      behavior. This peptide forms at the electrode two distinct films, depending on
      the concentration and accumulation time. The low-coverage film, composed of flat
      lying molecules (area per molecule of approximately 250-290 A(2)), yields a well
      defined catalytic peak at potentials around -1.75 V. The high-coverage film, made
      of upright-oriented peptides (area per molecule of approximately 43 A(2)), is
      catalytically more active and the peak is observed at potentials less negative by
      approximately 0.4 V. The higher activity, evidenced by constant-current
      chronopotentiometry and cyclic voltammetry, is attributed to an increase in the
      acid dissociation constant of the amino acid residues as a result of the low
      permittivity of the interfacial region, as inferred from impedance measurements.
      An analogy is made to the known differences in acidic-basic behaviors of solvent
      exposed and hydrophobic domains of proteins.

PMID- 19743827
TI  - Programmable permanent data storage characteristics of nanoscale thin films of a
      thermally stable aromatic polyimide.
AB  - We have synthesized a new thermally and dimensionally stable polyimide, poly(4,4'
      amino(4-hydroxyphenyl)diphenylene hexafluoroisopropylidenediphthalimide) (6F-HTPA
      PI). 6F-HTPA PI is soluble in organic solvents and is thus easily processed with
      conventional solution coating techniques to produce good quality nanoscale thin
      films. Devices fabricated with nanoscale thin PI films with thicknesses less than
      77 nm exhibit excellent unipolar write-once-read-many-times (WORM) memory
      behavior with a high ON/OFF current ratio of up to 10(6), a long retention time
      and low power consumption, less than +/-3.0 V. Furthermore, these WORM
      characteristics were found to persist even at high temperatures up to 150 degrees
      C. The WORM memory behavior was found to be governed by trap-limited space-charge
      limited conduction and local filament formation. The conduction processes are
      dominated by hole injection. Thus the hydroxytriphenylamine moieties of the PI
      polymer might play a key role as hole trapping sites in the observed WORM memory
      behavior. The properties of 6F-HTPA PI make it a promising material for high
      density and very stable programmable permanent data storage devices with low
      power consumption.

PMID- 19743828
TI  - Efficient hydrolysis of organotrifluoroborates via silica gel and water.
AB  - A general, mild, and efficient method for the hydrolysis of
      organotrifluoroborates to unveil boronic acids using silica gel and H(2)O was
      developed. This method proved to be tolerant of a broad range of aryl-,
      heteroaryl-, alkenyl-, and alkyltrifluoroborates as well as structurally diverse
      aminomethylated organotrifluoroborates. As anticipated, electron-rich substrates
      provided the corresponding boronic acids more readily than electron-poor
      substrates, owing to the resonance-stabilized difluoroborane intermediate. The
      method developed was expanded further for the conversion of
      organotrifluoroborates to the corresponding boronate esters.

PMID- 19743829
TI  - A study of the interactions of ternary surfactant systems at the water-air
      interface.
AB  - Surface tension measurements were carried out for the systems containing ternary
      mixtures of cetyltrimethylammonium bromide (CTAB) and p-(1,1,3,3
      tetramethylbutyl)phenoxypoly(ethylene glycols), Triton X-100 (TX100) and Triton X
      165 (TX165). The aqueous solution of ternary surfactant mixtures were prepared by
      adding the third surfactant to the binary mixture of the surfactants where the
      synergetic effect in the reduction of the surface tension of water were
      determined to compare the influence of the third surfactants on the adsorption of
      this binary mixture at the water-air interface. The obtained results and
      calculations indicate that the synergetic effect in the reduction of the surface
      tension of water was deepened after adding the third surfactant to the binary
      mixture at the composition at which this effect was observed. The best synergetic
      effect in the gamma(LV) reduction was determined on the basis of the values of
      the molecular interaction parameter for aqueous solutions of ternary mixtures of
      CTAB+TX165 (alpha CTAB = 0.2) (gamma(LV) = 50 mN/m, C = 4.3 x 10(-5) M) +TX100
      (C=10(8)-10(-2) M).

PMID- 19743830
TI  - The critical role of surfactants in the growth of cobalt nanoparticles.
AB  - We report a combined experimental and computational study on the critical role of
      surfactants in the nucleation and growth of Co nanoparticles synthesized by
      chemical routes. By varying the surfactant species, Co nanoparticles of different
      morphologies under similar reaction conditions (e.g., temperature and Co
      precursor concentration) were produced. Depending on the surfactant species, the
      growth of Co nanoparticles followed three different growth pathways. For example,
      with surfactants oleic acid (OA) and trioctylphosphine oxide (TOPO) used in
      combination, Co nanoparticles followed a diffusional growth pathway, leading to
      single crystalline nanoparticles. Multiple-grained nanoparticles, through an
      aggregation process, were formed with the combination of surfactants OA and
      dioctylamine (DOA). Further, an Ostwald ripening process was observed in the case
      of TOPO alone. Complementary electronic structure calculations were used to
      predict the optimized Co-surfactant complex structures and to quantify the
      binding energy between the surfactants (ligands) and the Co atoms. These
      calculations were further applied to predict the Co nanoparticle nucleation and
      growth processes based on the stability of Co-surfactant complexes.

PMID- 19743831
TI  - Ordered cubic mesoporous silicas with large pore sizes synthesized via high
      temperature route.
AB  - Ordered cubic mesoporous silicas with large pore sizes (LP-SBA-16) have been
      successfully synthesized at high temperatures (180-220 degrees C) using polymer
      surfactant of F127 as a template. Compared with conventional SBA-16 with entrance
      size at 3.6 nm, LP-SBA-16 samples synthesized at high temperatures show large
      entrance sizes at 11.8-24.7 nm, confirmed by the pore size distribution and TEM
      images. The formation of these large pore sizes in the samples is attributed to
      the increase of surfactant hydrophobicity and the merging of mesopores at high
      temperatures. The results obtained from NMR and XRD techniques show that ordered
      mesostructure in LP-SBA-16 samples basically remained even if the surfactant
      (F127) is fully decomposed at high temperatures, indicating that F127 surfactant
      becomes unimportant when the mesoporous walls of silica have been condensed.
      Furthermore, we have compared the adsorption capacity of myoglobin over
      conventional SBA-16 and LP-SBA-16 samples, and it is found that LP-SBA-16 samples
      exhibit much higher adsorption capacity than conventional SBA-16, which is
      potentially important for immobilization of enzymes on ordered mesoporous
      materials.

PMID- 19743832
TI  - Capturing the motion of molecular nanomaterials encapsulated within carbon
      nanotubes with ultrahigh temporal resolution.
AB  - We use in situ low-voltage aberration corrected high resolution transmission
      electron microscopy with a temporal resolution of 80 ms to track the motional
      dynamics of nanostructures encapsulated within carbon nanotubes. Two different
      nanostructures are examined and both are produced by electron beam irradiation of
      peapods containing La@C(82) metallofullerenes. The first novel nanostructure
      consists of a LaC(2) metal cluster attached to carbon nanotube inside a nanotube
      host. It exhibits repeated nanopiston-like behavior over a 5 min duration, driven
      by energy supplied by electron beam irradiation. Interaction of the metal cluster
      with the nanotube host is also examined, revealing that the metal cluster can
      open up the nanotube sidewall, exit, and then seal the hole in the wall back up
      with carbon from the surrounding region. Finally, the intrinsic motional dynamics
      of an isolated single fullerene within a SWNT is captured and we report
      velocities up to 112 nm/s.

PMID- 19743833
TI  - Near-ideal strength in gold nanowires achieved through microstructural design.
AB  - The ideal strength of crystalline solids refers to the stress at elastic
      instability of a hypothetical defect-free crystal with infinite dimensions
      subjected to an increasing load. Experimentally observed metallic wires of a few
      tens of nanometers in diameter usually yield far before the ideal strength,
      because different types of surface or structural defects, such as surface
      inhomogeneities or grain boundaries, act to decrease the stress required for
      dislocation nucleation and irreversible deformation. In this study, however, we
      report on atomistic simulations of near-ideal strength in pure Au nanowires with
      complex faceted structures related to realistic nanowires. The microstructure
      dependence of tensile strength in face-centered cubic Au nanowires with either
      cylindrical or faceted surface morphologies was studied by classical molecular
      dynamics simulations. We demonstrate that maximum strength and steep size effects
      from the twin boundary spacing are best achieved in zigzag Au nanowires made of a
      parallel arrangement of coherent twin boundaries along the axis, and {111}
      surface facets. Surface faceting in Au NWs gives rise to a novel yielding
      mechanism associated with the nucleation and propagation of full dislocations
      along {001}110 slip systems, instead of the common {111}112 partial slip observed
      in face-centered cubic metals. Furthermore, a shift from surface dislocation
      nucleation to homogeneous dislocation nucleation arises as the twin boundary
      spacing is decreased below a critical limit in faceted nanowires. It is thus
      discovered that special defects can be utilized to approach the ideal strength of
      gold in nanowires by microstructural design.

PMID- 19743834
TI  - Molecular symmetry and isostructural relations in crystal phases of
      trihalomethanes CHCl3, CHBrCl2, CHBr2Cl, and CHBr3.
AB  - Bromodichloromethane (CHBrCl(2)), dibromochloromethane (CHBr(2)Cl), and their
      parent trihalomethanes, chloroform (CHCl(3)) and bromoform (CHBr(3)), form an
      intriguing series of isostructural crystal phases, the sequence of which depends
      on the Br/Cl substitution and thermodynamic conditions. The phase behavior of
      these compounds has been studied by isobaric calorimetry and isothermal
      compression, and the crystal structure of CHBrCl(2) has been determined at 0.10
      MPa/200 K, 0.73, 1.26, 2.53 GPa (all at 295 K), and that of CHBr(2)Cl at 0.43,
      1.24 GPa (all at 295 K). CHBrCl(2) frozen by isobaric cooling at 0.10 MPa
      crystallizes in space group P1 with Z = 2, while its high-pressure polymorph in
      space group Pnma (Z = 4) is stable at 295 K from its freezing pressure at 0.48 to
      at least 2.53 GPa. At the freezing pressure of 0.29 GPa, CHBr(2)Cl crystallizes
      in space group P6(3), with Z = 2, and at 1.27 GPa, it transforms to the
      orthorhombic structure, space group Pnma (Z = 4); CHCl(3) has the identical
      symmetries, but their reverse sequence was observed. A subtle isostructural phase
      transition has been observed at 0.10 MPa and 214.9 K in CHBr(2)Cl. The relations
      between isostructural phases, their symmetry, and site occupation factors of
      halogen atoms observed in the low-temperature and high-pressure phases of
      trihalomethanes (CHCl(3), CHBrCl(2), CHBr(2)Cl, and CHBr(3)) have been explained
      by the directional character of electrostatic interactions between the molecules.
      A gradual ordering of the disordered Br and Cl atoms has been achieved in the
      compressed crystals, where the narrower volume of the atomic sites correlates
      with the increased occupancy of the smaller atom (chlorine). The molecular
      symmetry has been shown to control the molecular aggregation in the crystalline
      state, consistent with the crystal site-symmetry and the balance of electrostatic
      matching and dispersion forces between molecules.

PMID- 19743835
TI  - Matching constituent fluxes for convective deposition of binary suspensions.
AB  - Rapid convective deposition is an effective method for depositing well-ordered
      monolayers from monodisperse suspensions; however, much less is known about
      polydisperse suspension deposition. The addition of a much smaller species can
      enhance deposition by extending the range of ordered deposition and can induce
      instability, producing stripes and other complex morphologies. By considering
      relative species flux, we predict the volume fraction ratio of smaller to larger
      constituents necessary for steady well-ordered deposition. Experiments varying
      the 1 microm microsphere and 100 nm nanoparticle concentrations exhibit an
      optimum nanoparticle to microsphere volume fraction ratio at moderate volume
      fractions that agrees well with theory. Average local bond order and surface
      density characterize crystallinity and coverage, respectively. At lower
      microsphere volume fraction, monolayer crystallinity is optimized at a constant
      nanoparticle volume fraction of 0.04. At lower-than-optimum nanoparticle
      concentrations for each microsphere concentration, instability occurs and
      alternating stripes of monolayer and submonolayer morphologies form. At higher
      than-optimum nanoparticle concentration, the microspheres become disordered
      and/or form multilayer regions. Additionally, the degree of microsphere burial in
      deposited nanoparticles depends solely on nanoparticle concentration.

PMID- 19743836
TI  - The stathmin-derived I19L peptide interacts with FtsZ and alters its bundling.
AB  - FtsZ is a prokaryotic tubulin-like protein. Despite a low degree of sequence
      identity with tubulin, it presents the same folding pattern and some similar
      functions, notably in cell division. Indeed, FtsZ and tubulin polymerize to form
      bundles and microtubules, respectively, which are essential for cell cytokinesis.
      We previously demonstrated that peptides derived from the N-terminal stathmin
      domain interact with tubulin and impede microtubule formation. We demonstrated
      here that I19L, the most efficient of these peptides, also alters FtsZ bundling
      assembly in vitro. STD-NMR and TRNOESY experiments revealed that I19L interacts
      with FtsZ and folds upon its binding but in a way different from what we observed
      with tubulin. These NMR data were used in molecular modeling calculations to
      propose models of the I19L-FtsZ complex. Interestingly, two models, consistent
      with NMR data, show an interaction of I19L near the T7 loop or near the GTP
      binding site of FtsZ, explaining the modifications of the bundling assembly
      observed with this peptide. The fine analysis of the structural differences of
      the complexes of I19L with FtsZ and tubulin should help for the rational
      development of new specific antibiotic agents.

PMID- 19743838
TI  - Surfactant-directed multiple anisotropic gold nanostructures: synthesis and
      surface-enhanced Raman scattering.
AB  - A facile and effective method for the synthesis of gold nanostructures using beta
      cyclodextrin in aqueous alkaline medium is reported. The results demonstrate that
      leaf-like, rugged, dendritic, and tadpole-shaped gold nanostructures are obtained
      with high yield for the first time under the same experimental conditions by
      using four different surfactants. To study the effect of surfactant on the shape
      of the nanoparticles, the experiments were also carried out in the absence of
      surfactant and in the presence of poly(1-vinyl-2-pyrrolidone). The growth process
      of the dendritic gold nanostructures formed was investigated by withdrawing
      samples from the heated solution and examining the intermediate products formed
      by transmission electron microscopic analysis. The formation mechanism of the
      anisotropic gold nanostructures is discussed, and it is demonstrated that the
      cooperative effect of cyclodextrin and the surfactant molecules determines the
      ultimate morphology of the gold nanostructures obtained. In addition, the effect
      of the as-prepared nanostructures as an active material in surface-enhanced Raman
      scattering has been investigated by employing 4-aminothiophenol as a probe
      molecule. Thus, different enhancement signals are obtained for the different
      nanostructures; the dendritic nanostructures showed the strongest intensity of
      the SERS signals and smallest for the leaf-like nanostructures.

PMID- 19743837
TI  - Conserved polar residues stabilize transmembrane domains and promote
      oligomerization in human nucleoside triphosphate diphosphohydrolase 3.
AB  - Polar residues play essential roles in the functions of transmembrane helices by
      mediating and stabilizing their helical interactions. To investigate the
      structural and functional roles of the conserved polar residues in the N- and C
      terminal transmembrane helices of human nucleoside triphosphate
      diphosphohydrolase 3 (NTPDase3) (N-terminus, S33, S39, T41, and Q44; C-terminus,
      T490, T495, and C501), each was singly mutated to alanine. The mutant proteins
      were analyzed for enzymatic activities, glycosylation status, expression level,
      and Triton X-100 detergent sensitivity. The Q44A mutation decreased Mg-ATPase
      activity by approximately 70% and abolished Triton X-100 detergent inhibition of
      Ca-dependent nucleotidase activities while greatly attenuating Triton X-100
      inhibition of Mg-dependent nucleotidase activities. The polar residues were also
      mutated to cysteine, singly and in pairs, to allow a disulfide cross-linking
      strategy to map potential inter- and intramolecular hydrogen bond interactions.
      The results support the centrality of Q44 for the strong intermolecular
      interactions driving the association of the N-terminal helices of two NTPDase3
      monomers in a dimer, and the possibility that T41 may play a role in the
      specificity of this interaction. In addition, S33 and C501 form an intramolecular
      association, while S39 and T495 may contribute to helical interactions involved
      in forming higher-order oligomers. Lastly, Tween 20 substantially and selectively
      increases NTPDase3 activity, mediated by the transmembrane helices containing the
      conserved polar residues. Taken together, the data suggest a model for putative
      hydrogen bond interactions of the conserved polar residues in the transmembrane
      domain of native, oligomeric NTPDase3. These interactions are important for
      proper protein expression, full enzymatic activity, and susceptibility to
      membrane perturbations.

PMID- 19743839
TI  - Thyroid hormone interactions with DMPC bilayers. A molecular dynamics study.
AB  - The structure and dynamics of thyroxine (T4), distal and proximal conformers of
      3',3,5-triiodo-l-thyronine (T3d and T3p), and 3,5-diiodo-l-thyronine (T2) upon
      interaction with DMPC membranes were analyzed by means of molecular dynamics
      simulations. The locations, the more stable orientations, and the structural
      changes adopted by the hormones in the lipid medium evidence that the progressive
      iodine substitution on the beta ring lowers both the possibility of penetration
      and the transversal mobility in the membrane. However, the results obtained for
      T3d show that the number of iodine atoms in the molecule is not the only relevant
      factor in the hormone behavior but also the orientation of the single iodine
      substitution. The electrostatic interactions between the zwitterion group of the
      hormones with specific groups in the hydrophilic region of the membrane as well
      as the organization of the alkyl chains around the aromatic beta ring of the
      hormone were evaluated in terms of several radial distribution functions.

PMID- 19743840
TI  - Macromolecule-induced assembly of coiled-coils in alternating multiblock
      polymers.
AB  - The bioconjugation of proteins and peptides with synthetic polymers is a
      promising method for tailoring the chemical, biological, and physical properties
      of both the polymeric and protein-based components. Here, we describe
      macromolecular assemblies of polyethylene glycol-coiled-coil alternating
      multiblock polymers guided by hetero- and homodimeric association of coiled
      coils. High molecular weight, alternating block polymers of polyethylene glycol
      (PEG) and coiled-coil peptides were formed via facile NHS-activated amide bond
      formation under strictly anhydrous conditions. Confirmation of multiblock
      formation was assessed via a combination of NMR spectroscopy, size-exclusion
      chromatography, and electrophoretic analysis. Formation of the alternating
      multiblock polymers of PEG with coiled-coil peptides through the f-position on
      the heptads did not impair the ability of the coiled-coils to form heterodimers,
      as assessed via circular dichroic spectroscopy. Interestingly, the conjugation
      triggered homooligomer formation in one of the peptides that is monomeric in the
      absence of PEG. The macromolecular assembly of the homooligomer was characterized
      via circular dichroic spectroscopy and analytical ultracentrifugation, as well as
      via dynamic and static light scattering. The assembled structures formed in
      phosphate buffered saline even at very dilute concentrations of multiblock
      polymer and exhibited controlled sizes relevant in applications such as drug
      delivery and controlled release.

PMID- 19743841
TI  - Preventing nonspecific adsorption on polymer brush covered gold electrodes using
      a modified ATRP initiator.
AB  - Biological systems have a tendency to adsorb nonspecifically onto a solid
      substrate, thus reducing the efficacy of the interface being used in
      biorecognition. This nonspecific adsorption is a common problem in the
      development of biosensors as it typically reduces the efficacy of the sensor
      platform. In this manuscript we report the synthesis of an oligo(ethylene glycol)
      (OEG) containing ATRP (atom transfer radical polymerization) thiol initiator and
      demonstrate the role of this initiator in preventing nonspecific adsorption of
      IgG antibodies on chemically functionalized gold electrode surfaces using cyclic
      voltammetry. A new synthetic route for the synthesis of the new ATRP thiol
      initiator in high yields has been reported. Surface initiated poly(acrylic acid)
      brushes grown off the gold surface with modified OEG containing and conventional
      ATRP thiol initiators were chemically modified with 2,4-dinitrophenyl (DNP)
      groups. Amperometric studies were carried out on gold electrodes modified with
      DNP-PAA brushes using DNP-specific and nonspecific IgG antibodies. The cyclic
      voltammograms of an osmium redox mediator recorded over time suggest that the
      chemical modification of the gold electrodes with DNP-PAA brushes using the OEG
      containing ATRP initiator is much more effective in preventing nonspecific
      adsorption of antibodies than polymer brushes grown from the conventional
      initiator. Finally, we confirmed these results with the quartz crystal
      microbalance (QCM) technique by quantitatively evaluating the adsorption of
      nonspecific IgG antibodies on DNP-PAA functionalized QCM surfaces. The use of
      this modified ATRP thiol initiator to chemically functionalize
      macro/microelectrode surfaces will help develop reproducible, reliable, and
      robust electrochemical biosensors with minimized nonspecific adsorption.

PMID- 19743842
TI  - Acceleration of osteogenic differentiation of preosteoblastic cells by chitosan
      containing nanofibrous scaffolds.
AB  - To accelerate bone tissue formation, scaffolds better provide stimulatory niches
      to the residing cells for osteogenic differentiation. In this study,
      polycaprolactone (PCL) nanofibers containing various amounts of chitosan (0, 3,
      9, and 23%) were prepared and evaluated for their osteogenic differentiation of
      preosteoblasts in 2D and 3D cultures. Characterization of the obtained nanofibers
      revealed that average fiber diameter, hydrophilicity, Young's modulus, and fiber
      degradation were closely correlated with the amount of chitosan in PCL
      nanofibers. Incorporation of chitosan in PCL nanofibers not only improved the
      adhesion and proliferation of MC 3T3-E1 cells but also elevated calcium
      deposition, alkaline phosphatase (ALP) activity, and the expression of
      osteopontin (OPN) compared to PCL alone nanofibers. Culture of cell-rich 3D
      constructs prepared by layer-by-layer assembling MC 3T3-E1 with chitosan
      containing PCL nanofibers led to a uniform tissue formation with significant
      mineralization at 21 days. In all, chitosan containing PCL nanofibers are
      superior to PCL nanofibers in promoting bone tissue formation.

PMID- 19743843
TI  - Bioreducible hyperbranched poly(amido amine)s for gene delivery.
AB  - A series of reducible hyperbranched poly(amido amine)s (RHB) with high
      transfection efficiency were designed and synthesized as nonviral gene delivery
      vectors. The polycations were synthesized by Michael addition copolymerization of
      N,N-dimethylaminodipropylenetriamine (DMDPTA) and two bisacrylamide monomers N,N'
      hexamethylene bisacrylamide (HMBA) and N,N'-cystamine bisacrylamide (CBA). The
      density of disulfide linkages in the synthesized hyperbranched polymers was tuned
      by varying the feed molar ratio of the bisacrylamide monomers. The results
      demonstrate that disulfide content in RHB controls the molecular weight of the
      polycation degradation products, ease of polyplex disassembly, polycation
      cytotoxicity, and polyplex transfection activity. Due to their lower
      cytotoxicity, polyplexes based on reducible polycations could be used safely in a
      wider range of DNA doses than nonreducible controls. As a result, significantly
      increased transfection activity is achieved with optimized formulations of
      reducible polyplexes compared with nonreducible controls.

PMID- 19743844
TI  - Grafting of zwitterion from cellulose membranes via ATRP for improving blood
      compatibility.
AB  - A p-vinylbenzyl sulfobetaine was grafted from cellulose membrane (CM) using
      surface-initiated atom transfer radical polymerization for blood compatibility
      improvement. Surface structure, wettability, morphology, and thermal stability of
      the CM substrates before and after modification were characterized by attenuated
      total reflectance Fourier transform infrared spectra, X-ray photoelectron
      spectroscopy measurement, water contact angle measurement, atomic force
      microscopy, and thermogravimetric analysis, respectively. The results showed that
      zwitterionic brushes were successfully fabricated on the CM surfaces, and the
      content of the grafted layer increased gradually with the polymerization time.
      The blood compatibility of the CM substrates was evaluated by protein adsorption
      tests and platelet adhesion tests in vitro. It was found that all the CMs
      functionalized with zwitterionic brush showed improved resistance to nonspecific
      protein adsorption and platelet adhesion, even though the grafting polymerization
      was conducted for several minutes.

PMID- 19743845
TI  - Accurate determination of order parameters from 1H,15N dipolar couplings in MAS
      solid-state NMR experiments.
AB  - A reliable site-specific estimate of the individual N-H bond lengths in the
      protein backbone is the fundamental basis of any relaxation experiment in
      solution and in the solid-state NMR. The N-H bond length can in principle be
      influenced by hydrogen bonding, which would result in an increased N-H distance.
      At the same time, dynamics in the backbone induces a reduction of the
      experimental dipolar coupling due to motional averaging. We present a 3D dipolar
      recoupling experiment in which the (1)H,(15)N dipolar coupling is reintroduced in
      the indirect dimension using phase-inverted CP to eliminate effects from rf
      inhomogeneity. We find no variation of the N-H dipolar coupling as a function of
      hydrogen bonding. Instead, variations in the (1)H,(15)N dipolar coupling seem to
      be due to dynamics of the protein backbone. This is supported by the observed
      correlation between the H(N)-N dipolar coupling and the amide proton chemical
      shift. The experiment is demonstrated for a perdeuterated sample of the alpha
      spectrin SH3 domain. Perdeuteration is a prerequisite to achieve high accuracy.
      The average error in the analysis of the H-N dipolar couplings is on the order of
      +/-370 Hz (+/-0.012 A) and can be as small as 150 Hz, corresponding to a
      variation of the bond length of +/-0.005 A.

PMID- 19743846
TI  - Hyperthermal O-atom exchange reaction O2 + CO2 through a CO4 intermediate.
AB  - O(2) and CO(2) do not react under ordinary conditions because of the
      thermodynamic stability of CO(2) and the large activation energy required for
      multiple double-bond cleavage. We present evidence for a gas-phase O-atom
      exchange reaction between neutral O(2) and CO(2) at elevated collision energies
      (approximately 160 kcal mol(-1)) from crossed-molecular-beam experiments.
      CCSD(T)/aug-cc-pVTZ calculations demonstrate that isotope exchange can occur on
      the ground triplet potential energy surface through a short-lived CO(4)
      intermediate that isomerizes via a symmetric CO(4) transition state containing a
      bridging oxygen atom. We propose a plausible adiabatic mechanism for this
      reaction supported by additional spin-density calculations.

PMID- 19743847
TI  - Broadband carbon-13 correlation spectra of microcrystalline proteins in very high
      magnetic fields.
AB  - PARIS recoupling irradiation, despite a low rf amplitude, can promote efficient
      magnetization transfer during solid-state NMR experiments at 900 MHz over a wide
      range of differences in isotropic chemical shifts in microcrystalline proteins.

PMID- 19743848
TI  - Controlling peptide folding with repulsive interactions between phosphorylated
      amino acids and tryptophan.
AB  - Phosphorylated amino acids were incorporated into a designed beta-hairpin peptide
      to study the effect on beta-hairpin structure when the phosphate group is
      positioned to interact with a tryptophan residue on the neighboring strand. The
      three commonly phosphorylated residues in biological systems, serine, threonine,
      and tyrosine, were studied in the same beta-hairpin system. It was found that
      phosphorylation destabilizes the hairpin structure by approximately 1.0 kcal/mol,
      regardless of the type of phosphorylated residue. In contrast, destabilization
      due to glutamic acid was about 0.3 kcal/mol. Double mutant cycles and pH studies
      are consistent with a repulsive interaction as the source of destabilization.
      These findings demonstrate a novel mechanism by which phosphorylation may
      influence protein structure and function.

PMID- 19743849
TI  - Multiple ultrafast, broadband 2D NMR spectra of hyperpolarized natural products.
AB  - The combination of ex situ dynamic nuclear polarization (DNP) with nuclear
      magnetic resonance (NMR) leads to signal-to-noise enhancements of 10(3)-10(4)
      compared to conventional NMR. Ex situ DNP, however, is ill-suited for collecting
      the array of transients needed in 2D NMR spectroscopy. Spatially encoded single
      scan 2D NMR methods can circumvent this drawback, yet these "ultrafast"
      experiments can cover spectral ranges of only approximately 20 ppm using
      conventional hardware. To deal with this limitation, we discuss here new
      spatial/spectral encoding strategies capable of folding (13)C resonances into the
      desired spectral windows. This new approach allows one to obtain--following a
      single hyperpolarization process--multiple 2D heteronuclear correlations arising
      from different (13)C regions. In combination with ex situ DNP, these principles
      enable the acquisition of HMBC and HSQC 2D NMR spectra on approximately 1 mM
      mixtures of natural products, characterizing with a high resolution sites spread
      over nearly 100 ppm bandwidths.

PMID- 19743850
TI  - Aromatic cation activation of alcohols: conversion to alkyl chlorides using
      dichlorodiphenylcyclopropene.
AB  - A novel paradigm for the activation of alcohols toward nucleophilic displacement
      via formation of cyclopropenium ethers is described. The conversion of a range of
      alcohol substrates to the corresponding alkyl chlorides occurs rapidly upon
      treatment with 3,3-dichloro-1,2-diphenylcyclopropene. (1)H NMR data support the
      intermediacy of a cyclopropenium intermediate, and the reaction is demonstrated
      to proceed primarily via the S(N)2 mechanism for 1-phenylethanol. A total of 12
      examples of substrate scope are provided.

PMID- 19743851
TI  - Mechanism of dimethylallyltryptophan synthase: evidence for a dimethylallyl
      cation intermediate in an aromatic prenyltransferase reaction.
AB  - Dimethylallyltryptophan synthase is an aromatic prenyltransferase that catalyzes
      an electrophilic aromatic substitution reaction between dimethylallyl diphosphate
      (DMAPP) and L-tryptophan. The synthase is found in a variety of fungi, where it
      catalyzes the first committed step in the biosynthesis of the ergot alkaloids.
      The enzymatic reaction could follow either a dissociative mechanism involving a
      discrete dimethylallyl cation intermediate or an associative mechanism in which
      the indole ring directly displaces diphosphate in a single step. In this work,
      positional isotope exchange (PIX) experiments are presented in support of a
      dissociative mechanism. When [1-(18)O]-DMAPP is subjected to the synthase
      reaction and recovered starting material is analyzed, 15% of the (18)O-label is
      found to have scrambled from a bridging to a nonbridging position on the alpha
      phosphorus. Kinetic isotope effect studies show that steps involved in the
      formation of the arenium ion intermediate are rate-determining, and therefore the
      scrambling occurs during the lifetime of the dimethylallyl cation/diphosphate ion
      pair. Similarly, when the unreactive substrate analogue, 6-fluorotryptophan, was
      employed, complete scrambling of the (18)O-label in DMAPP was observed. To our
      knowledge, this is the first observation of PIX in any prenyltransferase
      reaction, and it provides strong evidence supporting the existence of a
      carbocation intermediate.

PMID- 19743852
TI  - Crystallographic tailoring of graphene by nonmetal SiO(x) nanoparticles.
AB  - In this communication, we demonstrate nonmetal SiO(x) nanoparticles (NPs) can
      tailor few-layer graphenes (FLGs) into graphene nanoribbons (GNRs) and regular
      pieces with smooth edges. The tailoring of graphene is realized by the movements
      of SiO(x) NPs along the graphene lattice in the atmosphere of H(2), and the
      tailored trenches exhibit high selectivity of the crystallographic orientation
      compared to the reported metal NPs. The low tailoring rate and the long lifetime
      provide great potential for accurate control of the trench length or the length
      of the tailored GNRs. As a result, smooth GNRs with a length of several
      micrometers and a width narrower than 10 nm are obtained. A catalytic
      hydrogenation mechanism is proposed for the tailoring of graphene by SiO(x) NPs.
      These findings open up the possibility for atomically precise graphene device
      fabrication without metal contamination and indicate the potential catalytic
      activity of nonmetal NPs for the hydrogenation of carbon materials.

PMID- 19743853
TI  - Development of a novel immunoaffinity column for aflatoxin analysis using an
      organic solvent-tolerant monoclonal antibody.
AB  - An organic solvent-tolerant monoclonal antibody specific to aflatoxins B(1),
      B(2), G(1), G(2), and M(1) (AFB(1), AFB(2), AFG(1), AFG(2), and AFM(1)) was
      prepared. In an indirect competitive enzyme-linked immunosorbent assay, the half
      maximal inhibitory concentration (IC(50)) values were 1.9, 2.1, 2.1, 2.4, and 2.8
      ng/mL for AFB(1), AFB(2), AFG(1), AFG(2), and AFM(1), respectively. Antibody
      reactivity was retained at 40% methanol concentration or at acetonitrile
      concentrations up to 40%. An immunoaffinity column (IAC) was prepared using
      agarose gel beads with bound antibody. The IAC retained the tested AFs that were
      89, 90, 95, 90, and 89% for AFB(1), AFB(2), AFG(1), AFG(2), and AFM(1) at 20%
      acetonitrile concentrations or that were 81, 87, 79, and 83% for AFB(1), AFB(2),
      AFG(1), and AFG(2) at 60% methanol concentrations. Roasted peanuts and seven
      kinds of spices were spiked with 8.0, 1.0, 6.0, and 1.0 ng for AFB(1), AFB(2),
      AFG(1), and AFG(2) per 1 g sample and extracted with 90% acetonitrile. The
      roasted peanuts and cayenne pepper out of the spices were also extracted with 70%
      methanol. The extracts were diluted 5-fold with phosphate-buffered saline and
      applied to the IAC. The spiked aflatoxins were recovered with satisfactory rates:
      78 (RSD, 2.1%) to 127% (RSD, 1.7%). The developed IAC was used for the analysis
      of aflatoxins in naturally contaminated samples of roasted peanuts and cayenne
      pepper. The newly developed IAC showed substantially organic solvent tolerance at
      the concentration that could not be used for existing IACs, and the column showed
      good ability to clean up samples for food analysis.

PMID- 19743854
TI  - Controlled formation of concave tetrahedral/trigonal bipyramidal palladium
      nanocrystals.
AB  - Novel concave Pd nanocrystals with uniform diameter were successfully prepared in
      the presence of formaldehyde. While the outer surfaces of the as-prepared concave
      Pd nanocrystals are {111}, the faces concave toward the polyhedral center are
      high-surface-energy {110} faces. The degree of concavity and therefore the
      percentage of {110} of the nanocrystals are tunable by varying the amount of
      formaldehyde and the reaction temperature. Owing to the existence of active {110}
      facets, the electrocatalytic activity of the concave Pd nanocrystals displays
      dependency on their degree of concavity.

PMID- 19743855
TI  - Antioxidant capacity and lipid characterization of six Georgia-grown pomegranate
      cultivars.
AB  - Six pomegranate (Punica granatum) cultivars were investigated for their
      antioxidant capacity and lipid profile. Total polyphenols were determined
      according to the Folin-Ciocalteau method. Major organic acids and phenolic
      compounds were analyzed by RP-HPLC. Two in vitro antioxidant assays, ferric
      reducing antioxidant power and Trolox equivalent antioxidant capacity, were used
      to assess antioxidant capacity. Total lipid was extracted according to the Folch
      method, and fatty acid methyl esters were determined by GC. Tocopherols and
      phospholipids were identified and quantified by NP-HPLC using a fluorescence
      detector for tocopherols and an evaporative light scattering detector for
      phospholipid analysis. Phytosterols were analyzed by GC. The predominant organic
      acid was citric acid followed by malic acid. The peel fraction had the highest
      total hydrolyzable tannins content (4792.3-6894.8 mg/100 g of FW). Overall, the
      highest antioxidant capacity was found in leaves followed by peel, pulp, and
      seed. Pomegranate seed had an average lipid content of 19.2% with punicic acid as
      the predominant fatty acid. Pomegranate seed had high contents of alpha
      tocopherol (161.2-170.1 mg/100 g) and gamma-tocopherol (80.2-92.8 mg/100 g).

PMID- 19743856
TI  - Effect of temperature on lipid-related volatile production in tomato puree.
AB  - Lipid-related volatiles were measured in real time after the blending of grape
      tomatoes, using selected ion flow tube mass spectrometry (SIFT-MS). Measurements
      were made at 4, 23, or 37 degrees C. The volatiles in the headspace of the
      tomatoes, other than hexanal, increased with increasing temperature. The
      concentration of hexanal in the headspace increased from 4 to 23 degrees C, but
      decreased at 37 degrees C. The activity of hexanal-specific hydroperoxide lyase
      decreases at 37 degrees C. Moreover, precursors of hexanal may go through
      alternative pathways to form trans-2-heptenal and trans-2-octenal. The increase
      in concentration in the headspace for most volatiles can be explained by the
      increase in volatility, except for trans-2-heptenal, trans-2-octenal, and trans-2
      pentenal. These three volatiles appear to be generated at a much higher rate at
      37 degrees C due to the dominance of alternate pathways at this temperature.
      Temperature did not affect the time to peak level for most volatiles, except the
      time for hexanal was shorter with increasing temperature. A temperature-dependent
      lipoxygenase pathway was postulated.

PMID- 19743857
TI  - Effects of oral administration of yam tuber storage protein, dioscorin, to BALB/c
      mice for 21-days on immune responses.
AB  - Dioscorin, the tuber storage protein of yam, was reported to have
      immunomodulatory activity in RAW264.7 murine macrophage cell lines ( Food and
      Chemical Toxicology , 2007 , 45 , 2312 -2318 ). However, the immunomodulatory
      function of dioscorin after being ingested was not elucidated in vivo. Hence,
      BALB/c mice were given oral dioscorin (2.5 and 20 mg/kg/day) once a day for 21
      days. Lymphocyte subpopulation changes in the peripheral blood and splenocytes,
      stimulation in phagocytosis of the polymorphonuclear cell (PMN) and monocytes,
      the natural killer (NK) cell cytotoxicity, the splenocyte proliferation, and
      cytokine secretions in the presence of PHA were determined. The number changes of
      Peyer's patches and secreted IgA (sIgA) in the feces were determined. Oral
      dioscorin for 21-days increased the subpopulation in natural killer cells
      (CD49(+)) and/or B cells (CD19(+)), elevated the phagocytosis of PMN (p < 0.01)
      and MON (p < 0.01), and the NK cell cytotoxic activity (p < 0.05), and stimulated
      splenocyte proliferations in the presence of LPS or PHA (p < 0.05) in comparison
      with those of the control. Cytokines of INF-gamma, IL-4, and IL-10 secretions,
      the numbers of Peyer's patches, and sIgA in the feces showed higher levels in
      oral dioscorin and significant difference to those of the control (p < 0.001).
      These results suggested that dioscorin exhibited systemic and mucosal
      immunomodulatory activities after being ingested in vivo.

PMID- 19743858
TI  - Structure-activity relationship and molecular mechanisms of ethyl 2-amino-4-(2
      ethoxy-2-oxoethyl)-6-phenyl-4h-chromene-3-carboxylate (sha 14-1) and its
      analogues.
AB  - Rapid development of multiple drug resistance against current therapies is a
      major barrier in the treatment of cancer. Therefore, anticancer agents that can
      overcome acquired drug resistance in cancer cells are of great importance.
      Previously, we have demonstrated that ethyl 2-amino-4-(2-ethoxy-2-oxoethyl)-6
      phenyl-4H-chromene-3-carboxylate (5a, sHA 14-1), a stable analogue of ethyl 2
      amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate (6, HA 14
      1), mitigates drug resistance and synergizes with a variety of cancer therapies
      in leukemia cells. Structure-activity relationship (SAR) studies of 5a guided the
      development of ethyl 2-amino-6-(3',5'-dimethoxyphenyl)-4-(2-ethoxy-2-oxoethyl)-4H
      chromene-3-carboxylate (5q, CXL017), a compound with low micromolar cytotoxicity
      against a wide-range of hematologic and solid tumor cells. More excitingly, our
      studies of 5q in camptothecin (CCRF-CEM/C2) and mitoxantrone (HL-60/MX2)
      resistant cancer cells highlight its ability to selectively kill drug-resistant
      cells over parent cancer cells. 5q inhibits tumor cell growth through the
      induction of apoptosis, with detailed mechanism of its selectivity toward drug
      resistant cancer cells under investigation. These results suggest that 5q is a
      promising candidate for treatment of cancers with multiple drug resistance.

PMID- 19743859
TI  - Estimated dietary exposure of Canadians to perchlorate through the consumption of
      fruits and vegetables available in Ottawa markets.
AB  - There has been increasing concern over the contamination of drinking water and
      food with perchlorate. Studies have reported perchlorate in a variety of foods,
      including lettuce, milk, fruits, and juices. In this study, 150 food samples were
      analyzed by ion chromatography tandem mass spectrometry (IC-MS/MS) to determine
      the concentrations of perchlorate in imported and domestic fruits and vegetables
      available from retail outlets in Ottawa, Canada. Perchlorate was found in most of
      the tested food types with concentrations appearing to vary by commodity and
      country of origin. Levels ranged from nondetectable to 536 microg/kg, with
      Guatemalan cantaloupes (156 +/- 232 microg/kg), United States spinach (133 +/-
      24.9 microg/kg), Chilean green grapes (45.5 +/- 13.3 microg/kg), and United
      States Romaine lettuce (29.1 +/- 10.5 microg/kg) having the highest
      concentrations. Dietary exposure to perchlorate from analyzed fruits and
      vegetables was estimated to be approximately 36.6 and 41.1 ng/kg bw/day for
      toddlers (1-4 yrs) and children (5-11yrs), respectively.

PMID- 19743860
TI  - Discovery of novel antileishmanial agents in an attempt to synthesize pentamidine
      aplysinopsin hybrid molecule.
AB  - In an attempt to synthesize pentamidine-aplysinopsin hybrid molecule 25, a lead
      molecule 8 (containing Z-configured aplysinopsin moiety) was identified for
      antileishmanial activity. Optimization of lead 8 provided 24 (containing E
      configured aplysinopsin) possessing 10 times more activity and 401-fold less
      toxicity than the drug pentamidine in cell based assays. Synthesis of 24 was
      possible, surprisingly, because of two innate reactivities of indole-3
      carbaldehyde which provided it in diastereo- and regio-selectively pure form
      without recourse to the long reaction pathway.

PMID- 19743861
TI  - Synthesis and evaluation of lysophosphatidylserine analogues as inducers of mast
      cell degranulation. Potent activities of lysophosphatidylthreonine and its 2
      deoxy derivative.
AB  - In response to various exogenous stimuli, mast cells (MCs) release a wide variety
      of inflammatory mediators stored in their cytoplasmic granules and this release
      initiates subsequent allergic reactions. Lysophosphatidylserine (lysoPS) has been
      known as an exogenous inducer to potentiate histamine release from MCs, though
      even at submicromolar concentrations. In this study, through SAR studies on
      lysoPS against MC degranulation, we identified lysoPT, a threonine-containing
      lysophospholipid and its 2-deoxy derivative as novel strong agonists. LysoPT and
      its 2-deoxy derivative induced histamine release from MCs both in vitro and in
      vivo at a concentration less than one-tenth that of lysoPS. Notably, lysoPT did
      not activate a recently proposed lysoPS receptor on MCs, GPR34, demonstrating the
      presence of another undefined receptor reactive to both lysoPS and lysoPT that is
      involved in MC degranulation. Thus, the present strong agonists, lysoPT and its 2
      deoxy derivative, will be useful tools to understand the mechanisms of lysoPS
      induced activation of degranulation of MCs.

PMID- 19743862
TI  - Reactivity of the NO dimer: on the role of the triplet electronic states.
AB  - We performed ab initio calculations to investigate the lowest triplet and singlet
      electronic states of the NO dimer and their mutual spin-orbit couplings. The
      electronic structure calculations are done using multiconfigurational approaches
      and a large diffuse basis set. A high density of electronic states is found
      favoring their mutual interactions by vibronic and spin-orbit couplings. We used
      our potential curves and spin-orbit couplings to discuss the mechanisms for the
      IR dissociation and the UV photodissociation of the NO dimer and the electronic
      de-excitation of NO (A(2)Sigma(+)) after collision with NO (X(2)Pi). For these
      reactions, multistep pathways, which involve the long-range and the molecular
      regions of the potential energy surfaces of the triplet and singlet electronic
      states of N(2)O(2), are suggested. A qualitative agreement between our findings
      and previous experimental assumptions is found.

PMID- 19743863
TI  - Indolobenzazepin-7-ones and 6-, 8-, and 9-membered ring derivatives as tubulin
      polymerization inhibitors: synthesis and structure--activity relationship
      studies.
AB  - Several small weight indole derivatives (D-64131, D-24851, BPR0L075, BLF 61-3,
      and ATI derivatives) are potent tubulin polymerization inhibitors and show
      nanomolar antiproliferative activity. Among them, indolobenzazepin-7-ones were
      recently disclosed as potent antimitotic agents. In an effort to improve this
      structure, we prepared new derivatives in order to evaluate their
      antiproliferative activity. 5,6,7,9-Tetrahydro-8H-indolo[2,3-e][3]benzazocin-8
      one (1m) was found to be the most potent derivative inhibiting the cell growth of
      several cancer cell lines in the lower nanomolar range.

PMID- 19743864
TI  - Topological control of spin states in disjoint diradicals.
AB  - The meta- and para-bis-allylbenzene radical anions have been generated and
      investigated using mass spectrometry. The ions are formed by reaction of the
      corresponding bis-2-propenylbenzenes with atomic oxygen anion. Reactivity of the
      ions indicates that the ions most likely have a bis-allylbenzene structure.
      Reaction of the ions with carbon disulfide creates CS(2) adducts, which, upon
      collision-induced dissociation, decompose to regenerate the bis-allylbenzene
      anion or carbon disulfide radical anion. The branching ratios for the two
      products indicate differences in the electronic structures of the neutral bis
      allylbenzene diradicals. The difference in branching ratios and corresponding
      estimated electron affinities is interpreted in terms of different electronic
      states being formed, with the para diradical a singlet and the meta diradical
      either a ground-state triplet or a singlet with a very small singlet-triplet
      splitting. The difference in electron affinities is used to estimate a singlet
      triplet splitting of 0.06 eV for the para diradical. The studies show that
      topology can be used to control the electronic properties of disjoint,
      tetramethyleneethane (TME)-like diradicals.

PMID- 19743865
TI  - 2-Phenylpyrazolo[4,3-d]pyrimidin-7-one as a new scaffold to obtain potent and
      selective human A3 adenosine receptor antagonists: new insights into the receptor
      antagonist recognition.
AB  - A molecular simplification approach of previously reported 2-arylpyrazolo[3,4
      c]quinolin-4-ones was applied to design 2-arylpyrazolo[4,3-d]pyrimidin-7-one
      derivatives as new human A(3) adenosine receptor antagonists. Substituents with
      different lipophilicity and steric hindrance were introduced at the 5-position of
      the bicyclic scaffold (R(5) = H, Me, Et, Ph, CH(2)Ph) and on the 2-phenyl ring
      (OMe, Me). Most of the synthesized derivatives were highly potent hA(3) adenosine
      receptor antagonists, the best being the 2-(4-methoxyphenyl)pyrazolo[4,3
      d]pyrimidin-7-one (K(i) = 1.2 nM). The new compounds were also highly selective,
      being completely devoid of affinity toward hA(1), hA(2A), and hA(2B) adenosine
      receptors. On the basis of the recently published human A(2A) receptor
      crystallographic information, we propose a novel receptor-driven hypothesis to
      explain both A(3) AR affinity and A(3) versus A(2A) selectivity profiles of these
      new antagonists.

PMID- 19743866
TI  - Structure-activity relationships for substrate-based inhibitors of human
      complement factor B.
AB  - Human complement is a cascading network of plasma proteins important in immune
      defense, cooperatively effecting recognition, opsonization, destruction, and
      removal of pathogens and infected/damaged cells. Overstimulated or unregulated
      complement activation can result in immunoinflammatory diseases. Key serine
      proteases in this cascade are difficult to study due to their multiprotein
      composition, short lifetimes, formation on membranes, or serum circulation as
      inactive zymogens. Factor B is inactive at pH 7, but a catalytically active
      serine protease under alkaline conditions, enabling structure-activity
      relationship studies for 63 substrate-based peptide inhibitors with 4-7 residues
      and a C-terminal aldehyde. A potent factor B inhibitor was hexpeptide Ac-RLTbaLAR
      H (IC(50) 250 nM, pH 9.5), which at pH 7 also blocked formation of membrane
      attack complex via the "alternative pathway" of complement activation and
      inhibited human complement mediated lysis of rabbit erythrocytes. Inhibitors of
      factor B may be valuable probes and drug leads for complement mediated immunity
      and disease.

PMID- 19743867
TI  - Discovery of 1-[4-(3-chlorophenylamino)-1-methyl-1H-pyrrolo[3,2-c]pyridin-7-yl]-1
      morpholin-4-ylmethanone (GSK554418A), a brain penetrant 5-azaindole CB2 agonist
      for the treatment of chronic pain.
AB  - We report the synthesis and SAR of a series of novel azaindole CB(2) agonists. 6
      Azaindole 18 showed activity in an acute pain model but was inactive in a chronic
      model. 18 is a Pgp substrate with low brain penetration. The template was
      redesigned, and the resulting 5-azaindole 36 was a potent CB(2) agonist with high
      CNS penetration. This compound was efficacious in the acute model and the chronic
      joint pain model.

PMID- 19743869
TI  - Electrochemical correlation spectroscopy in nanofluidic cavities.
AB  - We introduce both theoretically and experimentally a new electrochemical
      technique based on measuring the fluctuations of the faradaic current during
      redox cycling. By analogy with fluorescence correlation spectroscopy (FCS), we
      refer to this technique as electrochemical correlation spectroscopy (ECS). We
      first derive an analytical expression of the power spectral density for the
      fluctuations in a thin-layer-cell geometry. We then show agreement with
      measurements using ferrocenedimethanol, Fc(MeOH)2, in water and in acetonitrile
      in microfabricated thin-layer cells with a approximately 70 nm electrode spacing.
      The fluctuation spectra provide detailed information about the adsorption
      dynamics of Fc(MeOH)2, which cause an apparent slowing of Brownian motion. We
      furthermore observe high-frequency fluctuations from which we estimate the rates
      of adsorption and desorption.

PMID- 19743870
TI  - Super-resolution laser scanning microscopy through spatiotemporal modulation.
AB  - Super-resolution optical microscopy has attracted great interest among
      researchers in many fields, especially in biology where the scale of physical
      structures and molecular processes fall below the diffraction limit of resolution
      for light. As one of the emerging techniques, structured illumination microscopy
      can double the resolution by shifting unresolvable spatial frequencies into the
      pass-band of the microscope through spatial frequency mixing with a wide-field
      structured illumination pattern. However, such a wide-field scheme typically can
      only image optically thin samples and is incompatible with multiphoton processes
      such as two-photon fluorescence, which require point scanning with a focused
      laser beam. Here, we propose two new super-resolution schemes for laser scanning
      microscopy by generalizing the concept of a spatially nonuniform imaging system.
      One scheme, scanning patterned illumination (SPIN) microscopy, employs modulation
      of the excitation combined with temporally cumulative imaging by a nondescanned
      array detector. The other scheme, scanning patterned detection (SPADE)
      microscopy, utilizes detection modulation together with spatially cumulative
      imaging, in this case by a nondescanned single-element detector. When combined
      with multiphoton excitation, both schemes can image thick samples with three
      dimensional optical sectioning and much improved resolution.

PMID- 19743871
TI  - Reshaping the plasmonic properties of an individual nanoparticle.
AB  - When symmetry is broken in plasmonic nanostructures, new optical properties
      emerge. Here we controllably reshape an individual Au nanoshell into a reduced
      symmetry nanoegg, then a semishell or nanocup by a novel electron-beam-induced
      ablation method, transforming its plasmonic properties. We follow the changes in
      the plasmonic response at the single nanostructure level throughout this
      reshaping process, observing the splitting of plasmon modes and the onset of
      electroinductive plasmons upon controlled, incremental opening of the outer
      metallic layer of the nanoparticle.

PMID- 19743872
TI  - DNA sequence detection using surface-enhanced resonance Raman spectroscopy in a
      homogeneous multiplexed assay.
AB  - Detection of specific DNA sequences is central to modern molecular biology and
      also to molecular diagnostics where identification of a particular disease is
      based on nucleic acid identification. Many methods exist, and fluorescence
      spectroscopy dominates the detection technologies employed with different assay
      formats. This study demonstrates the use of surface-enhanced resonance Raman
      scattering (SERRS) to detect specific DNA sequences when coupled with modified
      SERRS-active probes that have been designed to modify the affinity of double- and
      single-stranded DNA for the surface of silver nanoparticles resulting in
      discernible differences in the SERRS which can be correlated to the specific DNA
      hybridization event. The principle of the assay lies on the lack of affinity of
      double-stranded DNA for silver nanoparticle surfaces; therefore, hybridization of
      the probe to the target results in a reduction in the SERRS signal. Use of locked
      nucleic acid (LNA) residues in the DNA probes resulted in greater discrimination
      between exact match and mismatches when used in comparison to unmodified labeled
      DNA probes. Polymerase chain reaction (PCR) products were detected using this
      methodology, and ultimately a multiplex detection of sequences relating to a
      hospital-acquired infection, namely, methicillin-resistant Staphylococcus aureus
      (MRSA), demonstrated the versatility and applicability of this approach to real
      life situations.

PMID- 19743873
TI  - Non-trilinear chromatographic time retention-fluorescence emission data coupled
      to chemometric algorithms for the simultaneous determination of 10 polycyclic
      aromatic hydrocarbons in the presence of interferences.
AB  - Multivariate calibration coupled to high-performance liquid chromatography-fast
      scanning fluorescence spectroscopy (HPLC-FSFS) was employed for the analysis of
      10 selected polycyclic aromatic hydrocarbons (PAHs), six of which correspond to
      heavy PAHs. The goal of the present study was the successful resolution of a
      system even in the presence of real interferences. Second-order HPLC-FSFS data
      matrices were obtained in a short time with a chromatographic system operating in
      isocratic mode. The difficulties in aligning chromatographic bands in complex
      systems, such as the ones presented here, are discussed. Two second-order
      calibration algorithms which do not require chromatographic alignment were
      selected for data processing, namely, multivariate curve resolution-alternating
      least-squares (MCR-ALS) and parallel factor analysis 2 (PARAFAC2). These
      algorithms did also achieve the second-order advantage, and therefore they were
      able to overcome the problem of the presence of unexpected interferences. The
      study was employed for the discussion of the scopes of the applied second-order
      chemometric tools, demonstrating the superiority of MCR-ALS to successfully
      resolve this complex system. The quality of the proposed techniques was assessed
      on the basis of the analytical recoveries from different types of water and olive
      oil samples after solid-phase extraction. The studied concentration ranges in
      water samples were 5.6 x 10(-3)-0.20 ng mL(-1) for heavy PAHs and 0.036-0.80 ng
      mL(-1) for light PAHs, while in oil samples the PAHs concentrations were 0.13-9.6
      and 2.3-49.5 ng mL(-1) for heavy and light PAHS, respectively. All real samples
      were analyzed in the presence of the studied interferences.

PMID- 19743874
TI  - Role of hydrophobic and electrostatic interactions in coiled coil stability and
      specificity.
AB  - We have screened two coiled coil-forming libraries in which core a and
      electrostatic e/g positions have been partially randomized. We observed the
      relative ability of these residues to confer coiled coil stability using a
      protein-fragment complementation assay. Our studies continue with the Jun/Fos
      activator protein-1 (AP-1) leucine zipper complex, as it provides a valid
      therapeutic target, while representing one of the more simplistic examples of
      quaternary structure. In mammalian cells, 28 possible dimeric interactions result
      from combinations of cJun, JunB, JunD, cFos, FosB, Fra1, and Fra2. Consequently,
      peptides designed to target particular oncogenic members must bind with high
      affinity and also be specific if they are to function as desired. We have
      therefore tested the ability of core and electrostatic interactions to confer
      stable and specific peptides. A previously selected peptide (FosW) formed the
      template for the core and electrostatic libraries. The winner from the core
      randomization (FosW(Core)) bound specifically to cJun relative to cFos, FosB,
      Fra1, Fra2, and the FosW(Core) homodimer, as verified by thermal melting analyses
      and growth competitions in the presence of either a negative control "mock"
      peptide or a competitor fusion peptide (cFos-FosB-Fra1-Fra2). In contrast, the
      winner from the electrostatic e/g randomization (FosW(e/g)) bound to all
      respective complexes with high stability, suggesting that the more significant
      energetic contributions made by core residues may be enough to generate
      specificity as a consequence of positive design.

PMID- 19743875
TI  - Characterization of the CHK1 allosteric inhibitor binding site.
AB  - Checkpoint kinase 1 (CHK1) is a key element in the DNA damage response pathway
      and plays a crucial role in the S-G(2)-phase checkpoint. Inhibiting CHK1 is a
      therapeutic strategy involving abrogation of the G2/M mitotic checkpoint defense
      of tumor cells toward lethal damage induced by DNA-directed chemotherapeutic
      agents. To date, most CHK1 inhibition approaches have involved targeting the ATP
      site of this kinase. In this study, we provide crystallographic and kinetic
      characterization of two small molecule inhibitors that bind to an allosteric site
      in the proximity of the CHK1 substrate site. Analysis of kinetic and biophysical
      data has led to the conclusion that these small molecule allosteric site
      inhibitors of CHK1 are reversible and are neither ATP- nor peptide substrate
      competitive. K(i) values of 1.89 and 0.15 microM, respectively, have been
      determined for these compounds using a mixed inhibitor kinetic analysis.
      Cocrystal structures of the inhibitors bound to CHK1 reveal an allosteric site,
      unique to CHK1, located in the C-terminal domain and consisting of a shallow
      groove linked to a small hydrophobic pocket. The pocket displays induced fit
      characteristics in the presence of the two inhibitors. These findings establish
      the potential for the development of highly selective CHK1 inhibitors.

PMID- 19743876
TI  - Novel binding motif of ACTH analogues at the melanocortin receptors.
AB  - The melanocortin receptor (MCR) subtype family is a member of the GPCR
      superfamily, and each of them has a different pharmacological profile with regard
      to the relative potency of the endogenous and synthetic melanocortin peptides.
      Alpha-MSH and ACTH are endogenous nonselective agonists for MC1R, MC3R, MC4R, and
      MC5R. In this study, we examined the role of Phe(7) in ACTH on human (h) MC1R,
      MC3R, and MC4R binding and signaling. Our results indicate that substitution of
      Phe(7) with d-Nal(2')(7) in ACTH1-24 yields a pharmacological profile different
      from that for substitution of Phe(7) with d-Nal(2')(7) in MSH in hMC1R, hMC3R,
      and hMC4R. N-d-Nal(2')(7)-ACTH1-24 is an agonist at hMC3R and hMC4R which did not
      change the peptide from an agonist to an antagonist at hMC3R and hMC4R. Further
      experiments indicate that N-d-Nal(2')(7)-ACTH1-17 is the minimal peptide required
      for hMC3R and hMC4R activation. Single-amino acid substitution studies of d
      Nal(2')(7)-ACTH1-17 indicate that amino acid residues 15-17 in N-d-Nal(2')(7)
      ACTH1-17 are crucial for hMC3R and hMC4R activation. Substitutions of these amino
      acid residues reduced or abolished agonist activity at hMC3R and hMC4R.
      Conformational studies revealed a new beta-turn (Arg(8)-Trp(9)-Gly(10)-Lys(11))
      in N-d-Nal(2')(7)-ACTH1-17, compared to the beta-turn-like structure at NDP-alpha
      MSH (His(6)-d-Phe(7)-Arg(8)-Trp(9)). Our results suggest that NDP-alpha-MSH and N
      d-Nal(2')(7)-ACTH1-17 do not share the same binding site; the highly basic C
      terminal fragment (Lys(15)-Lys(16)-Arg(17)) of N-d-Nal(2')(7)-ACTH1-17 induced a
      new beta-turn, and this shift contributed the selective agonist activity at hMC3R
      and hMC4R.

PMID- 19743877
TI  - Synthesis of phthalocyanines-ALA conjugates: water-soluble compounds with low
      aggregation.
AB  - Syntheses of two water-soluble phthalocyanines (Pc) containing 5-aminolevulinic
      acid (ALA) linked to the core structure are described. These compounds were
      prepared by using original functionalizations, and they present remarkable
      structural and photophysical features, indicating that they could be applied to
      photodynamic therapy (PDT).

PMID- 19743878
TI  - Superheated water ion-exchange chromatography: an experimental approach for
      interpretation of separation selectivity in ion-exchange processes.
AB  - Cation-exchange selectivity for alkali and alkaline-earth metal ions and
      tetraalkylammonium ions on a strongly acidic sulfonic acid cation-exchange resin
      has been investigated in the temperature range of 40-175 degrees C using
      superheated water chromatography. Dependence of the distribution coefficient (ln
      KD) on the reciprocal of temperature (1/T) is not linear for most of the ions
      studied, and the selectivity coefficient for a pair of alkali metal ions or that
      of alkaline-earth metal ions approaches unity as temperature increases. On the
      other hand, the retention order of tetraalkylammonium ions is reversed at 160
      degrees C or above when eluted with Na2SO4 aqueous solution and the larger ions
      are eluted faster than the smaller ones contrary to the retention order obtained
      at ambient temperature. The change in ion-exchange selectivity with temperature
      observed with superheated water chromatography has been discussed on the basis of
      the effect of temperature on hydration of the ions and specific adsorption or
      distribution of ionic species between the external solution and ion-exchange
      resin. In superheated water, the electrostatic interaction or association of the
      ions with the fixed ion becomes a predominant mechanism resulting in different
      separation selectivity from that obtained at ambient temperature.

PMID- 19743879
TI  - Peptidic targeting of phosphatidylserine for the MRI detection of apoptosis in
      atherosclerotic plaques.
AB  - Molecular and cellular imaging of atherosclerosis has garnered more interest at
      the beginning of the 21st century, with aims to image in vivo biological
      properties of plaque lesions. Apoptosis seems an attractive target for the
      diagnosis of vulnerable atherosclerotic plaques prone to a thrombotic event. The
      aim of the present work was to screen for apoptosis peptide binders by phage
      display with the final purpose to detect apoptotic cells in atherosclerotic
      plaques by magnetic resonance imaging (MRI). A phosphatidylserine-specific
      peptide identified by phage display was thus used to design an MRI contrast agent
      (CA), which was evaluated as a potential in vivo reporter of apoptotic cells. A
      library of linear 6-mer random peptides was screened in vitro against immobilized
      phosphatidylserine. Phage DNA was isolated and sequenced, and the affinity of
      peptides for phosphatidylserine was evaluated by enzyme-linked immunosorbent
      assay. The phosphatidylserine-specific peptide and its scrambled homologue were
      attached to a linker and conjugated to DTPA-isothiocyanate. The products were
      purified by dialysis and by column chromatography and complexed with gadolinium
      chloride. After their evaluation using apoptotic cells and a mouse model of liver
      apoptosis, the phosphatidylserine-targeted CA was used to image atherosclerotic
      lesions on ApoE(-/-) transgenic mice. Apoptotic cells were detected on liver and
      aorta specimens by the immunostaining of phosphatidylserine and of active caspase
      3. Sequencing of the phage genome highlighted nine different peptides. Their
      alignment with amino acid sequences of relevant proteins revealed a frequent
      homology with Ca2+ channels, reminiscent of the function of annexins. Alignment
      with molecules involved in apoptosis provides a direct correlation between
      peptide selection and utility. The in vivo MRI studies performed at 4.7 T provide
      proof of concept that apoptosis-related pathologies could be diagnosed by MRI
      with a low molecular weight paramagnetic agent. The new CA could have real
      potential in the diagnosis and therapy monitoring of atherosclerotic disease and
      of other apoptosis-associated pathologies, such as cancer, ischemia, chronic
      inflammation, autoimmune disorders, transplant rejection, neurodegenerative
      disorders, and diabetes mellitus. The phage display-derived peptide could also
      play a potential therapeutic role through anticoagulant activity by mimicking the
      role of annexin V, the endogenous ligand of phosphatidylserine.

PMID- 19743880
TI  - Lipidic sponge phase crystal structure of a photosynthetic reaction center
      reveals lipids on the protein surface.
AB  - Membrane proteins are embedded in a lipid bilayer and maintain strong
      interactions with lipid molecules. Tightly bound lipids are responsible for
      vertical positioning and integration of proteins in the membrane and for assembly
      of multisubunit complexes and occasionally act as substrates. In this work we
      present the lipidic sponge phase crystal structure of the reaction center from
      Blastochloris viridis to 1.86 A, which reveals lipid molecules interacting with
      the protein surface. A diacylglycerol molecule is bound, through a thioether
      bond, to the N-terminus of the tetraheme cytochrome c subunit. From the electron
      density recovered at the Q(B) site and the observed change in recombination
      kinetics in lipidic sponge phase-grown crystals, the mobile ubiquinone appears to
      be displaced by a monoolein molecule. A 36 A long electron density feature is
      observed at the interface of transmembrane helices belonging to the H- and M
      subunits, probably arising from an unidentified lipid.

PMID- 19743881
TI  - Thermodynamic trends in carbon-hydrogen bond activation in nitriles and
      chloroalkanes at rhodium.
AB  - Several transition-metal systems have been used to establish correlations between
      metal-carbon and carbon-hydrogen bonds. Here, the [Tp'RhL] fragment, where Tp' =
      tris(3,5-dimethylpyrazolyl)borate and L = neopentyl isocyanide, is used to
      investigate C-H bond activation in a series of linear alkylnitriles and
      chloroalkanes. Using a combination of kinetic techniques, relative free energies
      can be found for the compounds TpRhL(CH(3))H, Tp'RhL[(CH(2))(n)CN]H (n = 1-5),
      and Tp'RhL[(CH(2))(m)Cl]H (m = 1, 3, 4, 5). It is found that the CN and Cl
      substituents dramatically strengthen the M-C bond more than anticipated if in the
      alpha-position, with the effect on bond strength diminishing substantially as the
      X group moves further from the metal (i.e, beta, gamma, delta). Examination of M
      C vs C-H bond strengths shows that the Tp'RhL(CH(2)X)H compounds (X = phenyl,
      vinyl, CN, Cl) all show a good correlation, as do the alkyl, aryl, and vinyl
      derivatives. The compounds in the former group, however, have stronger M-C bonds
      than expected based on the C-H bond strengths and consequently, their correlation
      is separate from the other unsubstituted compounds.

PMID- 19743882
TI  - Enantioselective synthesis and olfactory evaluation of bicyclic alpha- and gamma
      ionone derivatives: the 3D arrangement of key molecular features relevant to the
      violet odor of ionones.
AB  - Violet smelling ionones 1-3, occurring in the headspace of different flowers, are
      well-known perfumery raw materials. With the goal to recognize the still ill
      defined spatial arrangement of structural features relevant to the binding of
      ionones to olfactory G-protein coupled receptors, through B3LYP/6-31G(d) modeling
      studies we identified bicyclic compounds 7-9 as conformationally constrained 13
      alkyl-substituted analogues of monocyclic alpha- and gamma-ionones. They were
      thus synthesized to evaluate the olfactory properties. The enantioselective
      syntheses of 7-9 entailed two common key steps: (i) a Diels-Alder reaction to
      construct the octalinic core and (ii) a Julia-Lythgoe olefination to install the
      alpha,beta-enone side chain. The odor thresholds of synthetic 7 and 9 were
      significantly lower than the corresponding parent ionones, and 9 showed the
      lowest threshold value among violet-smelling odorants examined so far. Modeling
      studies suggested a nearly identical spatial orientation of key hydrophobic and
      polar moieties of compounds 1, 3, and 4-9. Presumably, interaction of these
      moieties with ionone olfactory receptors (ORs) triggers a similar receptor code
      that is ultimately interpreted by the human brain as a pleasant woody-violet
      smell. These results open the way to studies aimed at identifying and modeling
      complementary binding sites on alpha-helical domains of ionone receptor proteins.

PMID- 19743883
TI  - Synthesis of structurally simplified analogues of pancratistatin: truncation of
      the cyclitol ring.
AB  - Pancratistatin is a phenanthridone-type natural product isolated from several
      plants of the Amaryllidaceae family. Its potent antiproliferative, antivascular,
      antiviral, and antiparasitic properties have attracted the attention of
      synthetic, biological, and medicinal chemists. Pancratistatin's low natural
      availability and complex structure have steered many of these research projects
      toward the preparation of its simplified synthetic analogues with useful levels
      of activity. In this work we have developed synthetic chemistry aimed at the
      preparation of pancratistatin analogues with a truncated cyclitol portion of the
      molecule. The described synthetic pathways are based on a highly anti
      diastereoselective arylcuprate conjugate addition to gamma-alkoxy-alpha,beta
      enoates and syn-selective azidation at the alpha-position of ester enolates.
      Analogues with the formally cleaved C3-C4 bond, and thus containing an open ring
      C, as well as a compound containing a truncated lactol moiety in lieu of the
      cyclitol, were prepared. Several of the analogues exhibited weak
      antiproliferative activity, with the highest potency observed in the case of the
      lactol analogue. From these results implications for the design of future
      pancratistatin analogues are discussed. Furthermore, the synthetic pathways can
      be used to construct pancratistatin-mimetic libraries, in which the cyclitol
      moiety is replaced by other cyclic motifs.

PMID- 19743884
TI  - Biodistribution of HPMA copolymer-aminohexylgeldanamycin-RGDfK conjugates for
      prostate cancer drug delivery.
AB  - N-(2-Hydroxypropyl)methacrylamide (HPMA) copolymer-RGD (Arg-Gly-Asp) conjugates
      targeting the alpha(v)beta(3) integrin present on angiogenic blood vessels and
      some tumor types have shown increased accumulation in solid tumors and possess
      properties that suggest their use for site-specific drug delivery. Geldanamycin
      (GDM) is a benzoquinoid ansamycin that binds to heat-shock protein 90 (HSP90),
      effective for the treatment of multiple cancer types including prostate, but has
      dose-limiting cytotoxicity. We recently reported the synthesis of HPMA copolymer
      aminohexyl-geldanamycin (AH-GDM) conjugates containing RGDfK that demonstrated
      favorable properties of drug release, in vitro binding to the alpha(v)beta(3)
      integrin, cytotoxicity in human prostate cancer cells, and tolerability in nude
      mice greater than 2-fold equivalent free drug doses. In this study the
      biodistribution of 125I-radiolabeled HPMA copolymer-AH-GDM conjugates with and
      without RGDfK in both non-tumor-bearing and DU145 prostate tumor xenograft
      bearing nude mice was evaluated. At 60 mg/kg drug equivalent polymer doses in non
      tumor-bearing mice both conjugates showed fast elimination from blood and
      decreasing accumulation in all other organs. Kidney accumulation predominated and
      was higher for the conjugate containing RGDfK. In tumor-bearing mice, trace
      quantities of the conjugate containing RGDfK showed increased tumor accumulation
      as compared to the conjugate without RGDfK. Also evaluated were free drug
      concentrations in prostate tumor xenografts following treatments of 30 and 60
      mg/kg drug-equivalent copolymer conjugates (with and without RGDfK) compared with
      30 mg/kg free AH-GDM. Overall, 60 mg/kg treatment of RGDfK-containing conjugate
      showed significantly higher (p < 0.001) tumor drug concentrations compared with
      all other treatments. The targetable conjugates can effectively deliver higher
      amounts of geldanamycin to the tumor compared to nontargetable systems.

PMID- 19743885
TI  - Bioequivalence criteria for transdermal fentanyl generics: do these need a
      relook?
AB  - With the increasing appearance of transdermal fentanyl generics since 2004 when
      patent protection of the reference Duragesic expired, opportunities to switch
      between different generics have arisen. Transdermal fentanyl is subject to
      bioequivalence regulation because only approximately 92% of the dose is absorbed
      as a result of the need to maintain a diffusion gradient from plaster to skin.
      Considering the high potency of fentanyl and the potential dangerous adverse
      effects of full mu opioid receptor agonists, we assessed evidence suggesting a
      revision of the confidence limits of bioequivalence of 80-125%. A few cases have
      been reported where a prescribed ascension in transdermal fentanyl dosing
      triggered respiratory depression. Values of concentration that produce a 50%
      effective response for decreasing the ventilatory volume lie within the plasma
      concentration range of 1.4-2.5 ng/mL during transdermal fentanyl analgesia.
      However, an exchange of the reference with a generic with higher bioavailability
      would trigger respiratory depression only in extreme situations and is clinically
      supported by only a single case report. Experimental or clinical evidence is
      required to provide the necessary database for final judgement of bioequivalent
      limits of fentanyl generics. At present, the evidence is not sufficient to advise
      other bioequivalence criteria than those previously applied to transdermal
      fentanyl.

PMID- 19743886
TI  - Pharmacology of morphine in obese patients: clinical implications.
AB  - Morphine is an analgesic drug used to treat acute and chronic pain. Obesity is
      frequently associated with pain of various origins (e.g. arthritis, fibromyalgia,
      cancer), which increases the need for analgesic drugs. Obesity changes drug
      pharmacokinetics, and for certain drugs, specific modalities of prescription have
      been proposed for obese patients. However, scant data are available regarding the
      pharmacokinetics and pharmacodynamics of morphine in obesity. Prescription of
      morphine depends on pain relief but the occurrence of respiratory adverse effects
      correlates with obesity, and is not currently taken into account. Variations in
      the volume of distribution, elimination half-life and oral clearance of morphine,
      as well as recent advances in the respective roles of drug-metabolizing enzymes,
      catechol-O-methyltransferase and the mu opioid receptor in morphine
      pharmacokinetics and pharmacodynamics, may contribute to differences between
      obese and non-obese patients. In addition, drug-drug interactions may alter the
      disposition of morphine and its glucuronide metabolites, which may either
      increase the risk of adverse effects or reduce drug efficacy.

PMID- 19743887
TI  - A proposal for a pharmacokinetic interaction significance classification system
      (PISCS) based on predicted drug exposure changes and its potential application to
      alert classifications in product labelling.
AB  - BACKGROUND AND OBJECTIVE: Pharmacokinetic drug-drug interactions (DDIs) are one
      of the major causes of adverse events in pharmacotherapy, and systematic
      prediction of the clinical relevance of DDIs is an issue of significant clinical
      importance. In a previous study, total exposure changes of many substrate drugs
      of cytochrome P450 (CYP) 3A4 caused by coadministration of inhibitor drugs were
      successfully predicted by using in vivo information. In order to exploit these
      predictions in daily pharmacotherapy, the clinical significance of the
      pharmacokinetic changes needs to be carefully evaluated. The aim of the present
      study was to construct a pharmacokinetic interaction significance classification
      system (PISCS) in which the clinical significance of DDIs was considered with
      pharmacokinetic changes in a systematic manner. Furthermore, the classifications
      proposed by PISCS were compared in a detailed manner with current alert
      classifications in the product labelling or the summary of product
      characteristics used in Japan, the US and the UK. METHODS: A matrix table was
      composed by stratifying two basic parameters of the prediction: the contribution
      ratio of CYP3A4 to the oral clearance of substrates (CR), and the inhibition
      ratio of inhibitors (IR). The total exposure increase was estimated for each cell
      in the table by associating CR and IR values, and the cells were categorized into
      nine zones according to the magnitude of the exposure increase. Then,
      correspondences between the DDI significance and the zones were determined for
      each drug group considering the observed exposure changes and the current
      classification in the product labelling. Substrate drugs of CYP3A4 selected from
      three therapeutic groups, i.e. HMG-CoA reductase inhibitors (statins), calcium
      channel antagonists/blockers (CCBs) and benzodiazepines (BZPs), were analysed as
      representative examples. The product labelling descriptions of drugs in Japan, US
      and UK were obtained from the websites of each regulatory body. RESULTS: Among
      220 combinations of drugs investigated, estimated exposure changes were more than
      5-fold for 41 combinations in which ten combinations were not alerted in the
      product labelling at least in one country; these involved buspirone, nisoldipine
      and felodipine as substrates, and ketoconazole, voriconazole, telithromycin,
      clarithromycin and nefazodone as inhibitors. For those drug combinations, the
      alert classifications were anticipated as potentially inappropriate. In the
      current product labelling, many inter-country differences were also noted.
      Considering the relationships between previously observed exposure changes and
      the current alert classifications, the boundaries between 'contraindication' and
      'warning/caution' were determined as a 7-fold exposure increase for statins and
      CCBs, and as a 4-fold increase for BZPs. PISCS clearly discriminated these drug
      combinations in accordance with the determined boundaries. Classifications by
      PISCS were expected to be valid even for future drugs because the classifications
      were made by zones, not by designating individual drugs. CONCLUSION: The present
      analysis suggested that many current alert classifications were potentially
      inappropriate especially for drug combinations where pharmacokinetics had not
      been evaluated. It is expected that PISCS would contribute to constructing a leak
      less alerting system for a broad range of pharmacokinetic DDIs. Further
      validation of PISCS is required in clinical studies with key drug combinations,
      and its extension to other CYP and metabolizing enzymes remains to be achieved.

PMID- 19743888
TI  - Pharmacokinetic modelling and development of Bayesian estimators for therapeutic
      drug monitoring of mycophenolate mofetil in reduced-intensity haematopoietic stem
      cell transplantation.
AB  - BACKGROUND: Mycophenolate mofetil, a prodrug of mycophenolic acid (MPA), is used
      during non-myeloablative and reduced-intensity conditioning haematopoetic stem
      cell transplantation (HCT) to improve engraftment and reduce graft-versus-host
      disease (GVHD). However, information about MPA pharmacokinetics is sparse in this
      context and its use is still empirical. OBJECTIVES: To perform a pilot
      pharmacokinetic study and to develop maximum a posteriori Bayesian estimators
      (MAP-BEs) for the estimation of MPA exposure in HCT. PATIENTS AND METHODS:
      Fourteen patients administered oral mycophenolate mofetil 15 g/kg three times
      daily were included. Two consecutive 8-hour pharmacokinetic profiles were
      performed on the same day, 3 days before and 4 days after the HCT. One 8-hour
      pharmacokinetic profile was performed on day 27 after transplantation. For these
      8-hour pharmacokinetic profiles, blood samples were collected predose and 20, 40,
      60, 90 minutes and 2, 4, 6 and 8 hours post-dose. Using the iterative two-stage
      (ITS) method, two different one-compartment open pharmacokinetic models with
      first-order elimination were developed to describe the data: one with two gamma
      laws and one with three gamma laws to describe the absorption phase. For each
      pharmacokinetic profile, the Akaike information criterion (AIC) was calculated to
      evaluate model fitting. On the basis of the population pharmacokinetic
      parameters, MAP-BEs were developed for the estimation of MPA pharmacokinetics and
      area under the plasma concentration-time curve (AUC) from 0 to 8 hours at the
      different studied periods using a limited-sampling strategy. These MAP-BEs were
      then validated using a data-splitting method. RESULTS: The ITS approach allowed
      the development of MAP-BEs based either on 'double-gamma' or 'triple-gamma'
      models, the combination of which allowed correct estimation of MPA
      pharmacokinetics and AUC on the basis of a 20 minute-90 minute-240 minute
      sampling schedule. The mean bias of the Bayesian versus reference (trapezoidal)
      AUCs was <5% with <16% of the patients with absolute bias on AUC >20%. AIC was
      systematically calculated for the choice of the most appropriate model fitting
      the data. CONCLUSION: Pharmacokinetic models and MAP-BEs for mycophenolate
      mofetil when administered to HCT patients have been developed. In the studied
      population, they allowed the estimation of MPA exposure based on three blood
      samples, which could be helpful in conducting clinical trials for the
      optimization of MPA in reduced-intensity HCT. However, prior studies will be
      needed to validate them in larger populations.

PMID- 19743889
TI  - Effect of cytochrome P450 2D6 genotype on maternal paroxetine plasma
      concentrations during pregnancy.
AB  - BACKGROUND AND OBJECTIVE: Increasing numbers of women in childbearing years are
      treated with antidepressants. Concerns regarding fetal exposure to medication has
      led to large studies on drug effects on birth outcome and on the risk of
      congenital anomalies. The risk of adverse effects due to paroxetine use during
      pregnancy has been associated with the extent of exposure. Nevertheless, few
      studies have covered dosing aspects in order to minimize fetal antidepressant
      exposure while limiting the risk of treatment failure. Essential pharmacokinetic
      data in pregnancy are lacking, even regarding paroxetine, one of the most
      commonly used antidepressants. We examined the changes of maternal paroxetine
      concentrations during pregnancy in relation to cytochrome P450 (CYP) 2D6
      genotype. METHOD: An observational cohort study was conducted in 74 pregnant
      women aged from 25 to 45 years treated with paroxetine during pregnancy. Blood
      samples and information on dosing, weight, smoking and mood were provided at 16
      20, 27-31 and 36-40 weeks of pregnancy. Samples were analysed for paroxetine
      plasma concentrations and CYP2D6 genotype. RESULTS: Women who were genotyped as
      extensive metabolizers (EMs) or ultra-rapid metabolizers (UMs) for CYP2D6 (EM n =
      43; UM n = 1) showed steadily decreasing plasma paroxetine concentrations during
      the course of pregnancy, with a decrease of 0.3 microg/L (95% CI -0.58, -0.07)
      for each week of pregnancy. In contrast, plasma paroxetine concentrations of
      intermediate metabolizers (IMs [n = 25]) and poor metabolizers (PMs [n = 5])
      increased during pregnancy, resulting in an increase of 0.82 microg/L (95% CI
      0.42, 1.22) for each week of pregnancy. Weight gain, maternal age or smoking did
      not influence plasma drug concentrations. Decreasing plasma concentrations in EMs
      are in accordance with induced CYP2D6 activity during pregnancy. Accumulation of
      paroxetine in women with impaired CYP2D6 metabolism may be explained by
      competition with an endogenous substrate. In EMs/UMs the depressive symptoms
      increased significantly during the course of pregnancy, while in the IM/PM group
      these did not change. CONCLUSIONS: Differences in CYP2D6 genotype may have
      divergent effects on maternal plasma paroxetine concentrations during pregnancy,
      with therapeutic consequences. Accumulation of paroxetine in a considerable group
      of pregnant women will lead to unintended increased exposure of paroxetine to the
      unborn child. Knowledge about a patient's CYP2D6 genotype is indispensable when
      prescribing paroxetine in pregnancy [trialregister.nl Identifier ISRCTN25383361].

PMID- 19743890
TI  - Balsalazide: a novel 5-aminosalicylate prodrug for the treatment of active
      ulcerative colitis.
AB  - BACKGROUND: 5-Aminosalicylate (5-ASA) agents are the mainstay of oral therapy for
      ulcerative colitis (UC). Balsalazide, a prodrug of 5-ASA, has recently been
      approved for the treatment of UC. OBJECTIVE: To summarize current data on
      balsalazide and to discuss its impact on management of UC. METHODS: A systematic
      review of published literature was performed on PubMed using the search terms
      'Balsalazide' and 'Colazal(TM)'. The Cochrane database was also reviewed.
      RESULTS: Balsalzide, a 5-ASA prodrug, ulilizes azoreduction by colonic bacteria
      to achieve a sustained release of active 5-ASA throughout the colon. A recent
      clinical trial has demonstrated balsalazide 6.7 g/day to be superior to placebo
      in inducing remission in symptomatic UC. The drug is well tolerated with a safety
      profile comparable to other oral 5-ASA agents. The current data suggests that
      symptomatic remission occurs with both greater swiftness and greater frequency
      when compared with mesalamine. CONCLUSION: Balsalazide is approved for the
      treatment of mild-to-moderate active UC. It is efficacious for the induction of
      remission in mild to moderate UC and has a favorable safety profile, with the
      added advantages of greater efficacy of remission induction and rapidity of
      onset.

PMID- 19743891
TI  - Notch signaling in the hematopoietic system.
AB  - Because of its multiple effects in tissue homeostasis and cancer, Notch signaling
      is gaining increasing attention as a potential therapeutic target. Notch proteins
      belong to a family of highly conserved cell surface receptors. Ligand binding
      leads to proteolytic cleavage of Notch receptors by the gamma-secretase complex,
      followed by translocation of the active intracellular Notch domain into the
      nucleus and transcriptional activation. Multiple genetic and pharmacological
      methods are available to inhibit or activate the Notch pathway, some of which are
      entering human clinical trials. In this review, we discuss our current
      understanding of Notch signaling in the hematopoietic system. Canonical Notch
      signaling is essential for the generation of definitive embryonic hematopoietic
      stem cells, but dispensable for their maintenance during adult life. Notch
      controls several early steps of T cell development, as well as specific cell fate
      and differentiation decisions in other hematopoietic lineages. In addition,
      emerging evidence indicates that Notch is a potent, context-specific regulator of
      T cell immune responses, including in several disease models relevant to
      patients. This knowledge will constitute a framework to explore Notch modulation
      as a therapeutic strategy and to understand potential hematopoietic side effects
      of systemic Notch inhibition.

PMID- 19743892
TI  - Foamy virus vectors for gene transfer.
AB  - Foamy virus (FV) vectors are efficient gene delivery vehicles that have shown
      great promise for gene therapy in preclinical animal models. FVs or
      spumaretroviruses are not endemic in humans, but are prevalent in nonhuman
      primates and in other mammals. They have evolved means for efficient horizontal
      transmission in their host species without pathology. FV vectors have several
      unique properties that make them well suited for therapeutic gene transfer
      including a desirable safety profile, a broad tropism, a large transgene
      capacity, and the ability to persist in quiescent cells. They mediate efficient
      and stable gene transfer to hematopoietic stem cells (HSCs) in mouse models, and
      in the canine large animal model. Analysis of FV vector integration sites in
      vitro and in hematopoietic repopulating cells shows they have a unique
      integration profile, and suggests they may be safer than gammaretroviruses or
      lentiviral vectors. Here, properties of FVs relevant to the safety and efficacy
      of FV vectors are discussed. The development of FV vector systems is described,
      and studies evaluating their potential in vitro, and in small and large animal
      models, is reviewed.

PMID- 19743893
TI  - Systemic loxoscelism - not so quick!

PMID- 19743895
TI  - Therapeutic peptides for cancer therapy. Part II - cell cycle inhibitory peptides
      and apoptosis-inducing peptides.
AB  - BACKGROUND: Therapeutic peptides have great potential as anticancer agents owing
      to their ease of rational design and target specificity. However, their utility
      in vivo is limited by low stability and poor tumor penetration. OBJECTIVE: The
      authors review the development of peptide inhibitors with potential for cancer
      therapy. Peptides that arrest the cell cycle by mimicking CDK inhibitors or
      induce apoptosis directly are discussed. METHODS: The authors searched Medline
      for articles concerning the development of therapeutic peptides and their
      delivery. RESULTS/CONCLUSION: Inhibition of cancer cell proliferation directly
      using peptides that arrest the cell cycle or induce apoptosis is a promising
      strategy. Peptides can be designed that interact very specifically with cyclins
      and/or cyclin-dependent kinases and with members of apoptotic cascades. Use of
      these peptides is not limited by their design, as a rational approach to peptide
      design is much less challenging than the design of small molecule inhibitors of
      specific protein-protein interactions. However, the limitations of peptide
      therapy lie in the poor pharmacokinetic properties of these large, often charged
      molecules. Therefore, overcoming the drug delivery hurdles could open the door
      for effective peptide therapy, thus making an entirely new class of molecules
      useful as anticancer drugs.

PMID- 19743896
TI  - Modulation of neuropeptide Y receptors for the treatment of obesity.
AB  - BACKGROUND: Neuropeptide Y (NPY) has been demonstrated to have critical roles in
      the physiological control of appetite and energy homeostasis through NPY Y1, Y2,
      Y4 and Y5 receptors. A number of synthetic ligands for NPY receptor subtypes have
      been developed to date, with Y5 receptor antagonists and Y2 and Y4 receptor
      agonists advancing into clinical trials. METHODS: A survey of the scientific and
      patent literature since mid-2006 is presented. CONCLUSION: In addition to the
      specific modulation of respective NPY receptor subtypes, recent investigations
      have revealed that modulation of multiple NPY receptor subtypes produces additive
      or even synergistic anti-obesity effects. Development of reliable small molecule
      Y1, Y2 and Y4 receptor ligands would greatly accelerate investigations and drug
      discovery.

PMID- 19743894
TI  - Nanoparticles for biomedical imaging.
AB  - BACKGROUND: Synthetic nanoparticles are emerging as versatile tools in biomedical
      applications, particularly in the area of biomedical imaging. Nanoparticles 1 -
      100 nm in diameter have dimensions comparable to biological functional units.
      Diverse surface chemistries, unique magnetic properties, tunable absorption and
      emission properties, and recent advances in the synthesis and engineering of
      various nanoparticles suggest their potential as probes for early detection of
      diseases such as cancer. Surface functionalization has expanded further the
      potential of nanoparticles as probes for molecular imaging. OBJECTIVE: To
      summarize emerging research of nanoparticles for biomedical imaging with
      increased selectivity and reduced nonspecific uptake with increased spatial
      resolution containing stabilizers conjugated with targeting ligands. METHODS:
      This review summarizes recent technological advances in the synthesis of various
      nanoparticle probes, and surveys methods to improve the targeting of
      nanoparticles for their application in biomedical imaging. CONCLUSION: Structural
      design of nanomaterials for biomedical imaging continues to expand and diversify.
      Synthetic methods have aimed to control the size and surface characteristics of
      nanoparticles to control distribution, half-life and elimination. Although
      molecular imaging applications using nanoparticles are advancing into clinical
      applications, challenges such as storage stability and long-term toxicology
      should continue to be addressed.

PMID- 19743897
TI  - Poly(ADP-ribose) polymerase inhibition in cancer therapy: are we close to
      maturity?
AB  - BACKGROUND: During the last few years an increasing number of poly(ADP-ribose)
      polymerase (PARP) inhibitors have been appearing in the context of cancer
      therapy. This is mainly due to a better knowledge of the best-characterized
      member of the PARP family of enzymes, PARP-1, further reinforced by the
      recognition of the clinical benefits arising from its inhibition.
      OBJECTIVE/METHOD: The aim of this review is to give the reader an update on PARP
      inhibition in cancer therapy, by covering both the scientific (SciFinder) search)
      and the patent literature (Chemical Abstract/Derwent search) published recently
      (2005-2008). CONCLUSIONS: More patient-compliant orally available PARP-1
      inhibitor clinical candidates, along with their possible use as single agents in
      specific, molecularly defined cancer indications, increase the expectations for
      this therapeutic approach. The growing understanding of the biological role of
      other PARPs, such as Tankyrase 1, may be of interest as new potential targets.
      Besides the classical NAD-mimicking pharmacophore, additional compounds, which
      either do not resemble nicotinamide or exploit different binding sites, are
      emerging.

PMID- 19743898
TI  - Novel factor Xa inhibitors: a patent review.
AB  - IMPORTANCE OF THE FIELD: New oral anticoagulants with favorable safety profiles
      and fixed doses are required for the management of thromboembolism and stroke
      prevention in patients with atrial fibrillation. Among them, fXa inhibitors (the
      so-called xabans) are attractive options that can overcome limitations (e.g.,
      bleeding) of the current oral antithrombotic therapy. The rational design of
      small-molecule direct fXa inhibitors, whose importance is testified by the
      growing number of publications and patents recently registered, has been fully
      supported by the X-ray crystallography of enzyme-ligand complexes. AREAS COVERED
      IN THIS REVIEW: Pubmed, SciFinder Scholar, ISI web of knowledge(SM),
      http://ep.espacenet.com/ and Google websites were used as the main sources for
      literature retrieving, and > 100 patents filed between 2006 and April 2009,
      reviewed and discussed herein, highlight the variety among the P1 and P4 moieties
      on suitable scaffolds. WHAT THE READER WILL GAIN: The replacement of the
      benzamidine P1 moiety, which characterizes the first generation, with less basic
      bioisosteric or nonpolar neutral P1 groups led to the disclosure of numerous fXa
      inhibitors with high potency, selectivity and oral bioavailability. Novel
      selective fXa inhibitors with stable pharmacokinetics, better therapeutic windows
      and ease-of-use than the existing anticoagulants are currently under advanced
      stage clinical trials. TAKE-HOME MESSAGE: Available data from Phase II and Phase
      III studies reflect the drive towards fXa inhibitors as potentially more
      effective and safer antithrombotic drugs. Their development is expected to
      address two major needs for anticoagulation, namely safety and ease-of-use, and
      to significantly affect the anticoagulant market.

PMID- 19743899
TI  - Effectiveness of oral rinse with chlorhexidine in preventing nosocomial
      respiratory tract infections among intensive care unit patients.
AB  - OBJECTIVE: To evaluate the effectiveness of the oral application of a 0.12%
      solution of chlorhexidine for prevention of respiratory tract infections among
      intensive care unit (ICU) patients. DESIGN: The study design was a double-blind,
      randomized, placebo-controlled trial. SETTING: The study was performed in an ICU
      in a tertiary care hospital at a public university. PATIENTS. Study participants
      comprised 194 patients admitted to the ICU with a prospective length of stay
      greater than 48 hours, randomized into 2 groups: those who received chlorhexidine
      (n = 98) and those who received a placebo (n = 96). INTERVENTION: Oral rinses
      with chlorhexidine or a placebo were performed 3 times a day throughout the
      duration of the patient's stay in the ICU. Clinical data were collected
      prospectively. RESULTS: Both groups displayed similar baseline clinical features.
      The overall incidence of respiratory tract infections (RR, 1.0 [95% confidence
      interval [CI], 0.63-1.60]) and the rates of ventilator-associated pneumonia per
      1,000 ventilator-days were similar in both experimental and control groups (22.6
      vs 22.3; P = .95). Respiratory tract infection-free survival time (7.8 vs 6.9
      days; P = .61), duration of mechanical ventilation (11.1 vs 11.0 days; P = .61),
      and length of stay (9.7 vs 10.4 days; P = .67) did not differ between the
      chlorhexidine and placebo groups. However, patients in the chlorhexidine group
      exhibited a larger interval between ICU admission and onset of the first
      respiratory tract infection (11.3 vs 7.6 days; P = .05). The chances of surviving
      the ICU stay were similar (RR, 1.08 [95% CI, 0.72-1.63]). CONCLUSION: Oral
      application of a 0.12% solution of chlorhexidine does not prevent respiratory
      tract infections among ICU patients, although it may retard their onset.

PMID- 19743900
TI  - Epidemiology of methicillin-resistant Staphylococcus aureus in a university
      medical center day care facility.
AB  - OBJECTIVE: Few data are available on methicillin-resistant Staphylococcus aureus
      (MRSA) colonization in day care. We performed a study in a medical university
      child care center to study the epidemiology of MRSA in this population. DESIGN:
      Survey. SETTING: A child care center on the campus of a university medical
      center. METHODS: One hundred four children who attended the child care center and
      32 employees gave samples that were cultured for MRSA. Seventeen household
      members of the children and employee found to be colonized with MRSA also gave
      samples that were cultured. Parents and employees completed questionnaires about
      demographic characteristics, medical conditions and treatments, and possible
      exposure risks outside the child care center. In addition, 195 environmental
      samples were taken from sites at the childcare center. Isolates were analyzed for
      relatedness by use of molecular typing, and statistical analysis was performed.
      RESULTS: The prevalence of MRSA in the children was 6.7%. One employee (3.1%) was
      colonized with MRSA. Cultures of samples given by 6 of 17 (35.3%) family members
      of these children and the employee yielded MRSA. MRSA was recovered from 4 of 195
      environmental samples. Molecular typing revealed that many of the MRSA isolates
      were indistinguishable, and 18 of the 21 isolates were community-associated MRSA.
      Multivariable analysis revealed that receipt of macrolide antibiotics (P = .002;
      odds ratio, 39.6 [95% confidence interval, 3.4-651.4]) and receipt of asthma
      medications (P = .024; odds ratio, 26.9 [95% confidence interval, 1.5-500.7])
      were related to MRSA colonization. CONCLUSIONS: There was a low prevalence of
      MRSA colonization in children and employees in the child care center but a higher
      prevalence of colonization in their families. Molecular typing showed that
      transmission of MRSA likely occurred in the child care center. The use of
      macrolide antibiotics and asthma medications may increase the risk of MRSA
      colonization in this population.

PMID- 19743901
TI  - Pilot study of postexposure prophylaxis for hepatitis C virus in healthcare
      workers.
AB  - BACKGROUND AND OBJECTIVE: Hepatitis C virus (HCV) transmission occurs in 0.2%-10%
      of people after accidental needlestick exposures. However, postexposure
      prophylaxis is not currently recommended. We sought to determine the safety,
      tolerability, and acceptance of postexposure prophylaxis with peginterferon alfa
      2b in healthcare workers (HCWs) exposed to blood from HCV-infected patients.
      DESIGN: Open-label pilot trial of peginterferon alfa-2b for HCV postexposure
      prophylaxis. SETTING: Two academic tertiary-referral centers. METHODS: HCWs
      exposed to blood from HCV-infected patients were informed of the availability of
      postexposure prophylaxis. Persons who elected postexposure prophylaxis were given
      weekly doses of peginterferon alfa-2b for 4 weeks. RESULTS: Among 2,702 HCWs
      identified with potential exposures to bloodborne pathogens, 213 (7.9%) were
      exposed to an HCV antibody-positive source. Of 51 HCWs who enrolled in the study,
      44 (86%) elected to undergo postexposure prophylaxis (treated group). Seven
      subjects elected not to undergo postexposure prophylaxis (untreated group). No
      cases of HCV transmission were observed in either the treated or untreated group,
      and no cases occurred in the remaining 162 HCWs who did not enroll in this study.
      No serious adverse events related to a peginterferon alfa-2b regimen were
      recorded, but minor adverse events were frequent. CONCLUSION: In this pilot
      study, there was a lower than expected frequency of HCV transmission after
      accidental occupational exposure. Although peginterferon alfa-2b was safe,
      because of the lack of HCV transmission in either the treated or untreated groups
      there is little evidence to support routine postexposure prophylaxis against HCV
      in HCWs.

PMID- 19743905
TI  - Parity and breastfeeding in relation to obesity among black and white women in
      the southern community cohort study.
AB  - OBJECTIVE: This research sought to describe associations among parity,
      breastfeeding, and adult obesity in black and white women in the southeastern
      United States. METHODS: Cross-sectional data from 7,986 white women and 23,198
      black women (age 40-79 years) living in the southeastern United States and
      enrolled in the Southern Community Cohort Study during 2002-2006 were used to
      examine self-reported body mass index (BMI) and weight change since age 21 in
      association with parity and breastfeeding. Multiple linear regression and
      logistic regression with adjustment for demographic and lifestyle factors were
      used. RESULTS: At all levels of parity and breastfeeding, black women had higher
      BMI and weight gain since age 21 than white women. Compared to nulliparity, five
      or more live births was associated with increased odds of obesity in white women
      (odds ratio [OR] = 1.37, 95% confidence interval [CI] = 1.08-1.74) and, to a
      lesser extent, in black women (OR = 1.22, 95% CI = 1.07-1.38). In white women,
      breastfeeding for more than 12 months compared to none was associated with
      decreased odds of obesity (OR = 0.68, 95% CI = 0.56-0.82), whereas in black
      women, no association between obesity and breastfeeding was seen. CONCLUSIONS:
      The associations between childbearing factors and measures of adult obesity
      appear to be larger in white women compared to black women but relatively small
      overall. However, when considered as part of the constellation of factors that
      lead to obesity, even these small associations may be important in an overall
      obesity prevention strategy.

PMID- 19743906
TI  - Self-reported vulvar pain characteristics and their association with clinically
      confirmed vestibulodynia.
AB  - OBJECTIVE: We evaluated a series of questions pertaining to vulvar pain symptoms
      to determine their association with a localized vulvodynia (vestibulodynia)
      diagnosis in women from the general population. METHODS: A sample of 12,435 women
      completed a self-administered screening questionnaire for the presence of
      specific types and characteristics of vulvar pain lasting 3 months or longer.
      Sensitivity, specificity, and predictive values were calculated for each cross
      classification of vulvar pain type and characteristic, using as the gold standard
      121 subjects with a clinically confirmed vestibulodynia diagnosis. RESULTS:
      Relative to women with clinically confirmed vestibulodynia, 83% reported >10
      episodes of pain on contact at the time of tampon insertion, intercourse, or
      pelvic examination, and 83% also reported pain on contact that limited or
      prevented sexual intercourse. These strong associations with a vestibulodynia
      diagnosis were not observed with respect to women who reported vulvar pain
      symptoms of burning or knifelike pain, or vulvar pain characteristics of
      continuous versus intermittent pain, or provoked versus spontaneous pain.
      CONCLUSIONS: Our findings suggest that a small number of symptoms may be suitable
      for identifying a large proportion of women suffering from vestibulodynia which
      may be ideal for the development of an effective screening test in the future.
      However, we also recognize that a large proportion of women experiencing vulvar
      pain symptoms will not meet the diagnostic criteria for vestibulodynia. Thus,
      implementing such a screening procedure as part of a routine examination or
      testing would require a subsequent pelvic examination to confirm a vestibulodynia
      diagnosis and to rule out other known explanations for vulvar pain.

PMID- 19743907
TI  - Severity of interstitial cystitis symptoms and quality of life in female
      patients.
AB  - OBJECTIVE: Interstitial cystitis (IC) is a visceral pain syndrome with a profound
      impact on quality of life (QOL). The main aims of the current study are as
      follows: (1) to determine possible factors that may increase the severity of
      symptoms and decrease QOL in women diagnosed with IC; (2) to study how symptom
      severity affects QOL adjusting for these factors; and (3) to investigate which
      symptom is most likely to impair IC patients' physical and mental QOL. METHODS:
      Forty-one women (age, 20-71 years) with moderate/severe IC enrolled in a clinical
      trial of intravesical pentosan polysulfate sodium in California (USA) were
      included in this cross-sectional analysis. Demographic and clinical
      characteristics were evaluated at baseline using the O'Leary-Sant Interstitial
      Cystitis Symptom Index (ICSI), pain assessment, urgency scale, voiding log for 24
      h, and the Short Form-36 (SF-36). RESULTS: Being currently unmarried was
      associated with more severe symptoms. Being unemployed, currently unmarried,
      obese, never pregnant, and ever use of oral contraceptive were associated with a
      decrement in at least one QOL domain. Symptom severity was an independent
      predictor of worse QOL on three domains: bodily pain, general health, and mental
      health. Pain and nocturia were the only symptoms found to be associated with
      decline in overall physical quality of life. None of the symptoms had significant
      impact on the mental component summary of QOL. CONCLUSIONS: Symptom severity and
      being currently unmarried were found to be associated with impairment in QOL in
      IC patients. Managing pain and nocturia may improve the patients' overall
      physical QOL.

PMID- 19743908
TI  - Interdisciplinary curriculum to train internal medicine and obstetrics-gynecology
      residents in ambulatory women's health: adapting problem-based learning to
      residency education.
AB  - OBJECTIVE: Although residents in internal medicine (IM) and obstetrics-gynecology
      (OG) must provide primary care for women, studies indicate that both groups
      require more skills and training in women's health. Our goals were to assess the
      needs of residents at our academic medical center and to design an
      interdisciplinary curriculum that addresses these needs utilizing a modified
      problem-based learning (PBL) format. The aim of this article is to report on the
      development, logistics, and successful implementation of our innovative
      curriculum. METHODS: Based on results from a targeted needs-assessment, we
      designed a curriculum for both IM and OG residents to address curricular
      deficiencies in an efficient and effective manner. Procurement of support was
      achieved by reviewing overlapping competency requirements and results of the
      needs-assessment with the program directors. The curriculum consists of six
      ambulatory clinical cases which lead residents through a discussion of screening,
      diagnosis, prevention, and management within a modified PBL format. Residents
      select one learning objective each week which allows them to serve as content
      experts during case discussions, applying what they learned from their literature
      review to guide the group as they decide upon the next step for the case. This
      format helps accommodate different experience levels of learners, encourages
      discussion from less-vocal residents, and utilizes theories of adult learning.
      RESULTS: Sixty-five residents have participated in the curriculum since it was
      successfully implemented. IM residents report that the cases were their first
      opportunity to discuss the health concerns of younger women; OG residents felt
      similarly about cases related to older women. Implementation challenges included
      resident accountability. Residents identified the timing of the sessions and
      clinical coverage requirements as barriers to conference attendance. CONCLUSIONS:
      Interdisciplinary modified PBL conferences focusing on shared curricular needs in
      ambulatory women's health are well-received by both IM and OG residents. This
      format utilizes theories of adult learning and maximizes limited time and
      resources by teaching IM and OG residents concurrently, and can be successfully
      implemented at a large academic medical center.

PMID- 19743909
TI  - Microbicide acceptability among female sex workers in Beijing, China: results
      from a pilot study.
AB  - OBJECTIVES: To explore attitudes toward hypothetical vaginal microbicides and
      willingness to use them among female sex workers (FSWs) in a district of Beijing,
      China, and to identify factors likely to affect acceptability and use of
      microbicides for HIV prevention among this population. METHODS: An exploratory
      cross-sectional study using convenience sampling was conducted. A total of 54
      FSWs were recruited from Shijingshan District in Beijing for a face-to-face
      interview. Main outcome variables were measured by a microbicide acceptability
      score, perception of HIV/STI risk and self-reported high-risk sexual behaviors,
      condom use, HIV/STI history, and self-reported experience of vaginal product use.
      RESULTS: Mean score of microbicide acceptability in FSWs was 2.73, with a
      standard deviation (SD) of 0.46 (ranging from 1 to 4). Acceptability score varied
      by partner types (p = 0.025), history of HIV testing (p = 0.037), and concern
      about contracting an STI (p = 0.042). Covert use of microbicides in FSWs with
      various sexual partners was statistically different (p = 0.001). FSWs preferred
      to pay for microbicides and to use them covertly. CONCLUSIONS: In general, FSWs
      in Shijinghsan District might have a positive response to microbicides across all
      hypothetical characteristics. Further study is needed for comprehensive
      understanding of the contextual factors of microbicide use.

PMID- 19743910
TI  - Eating disorders and obstetric-gynecologic care.
AB  - OBJECTIVE: Disordered eating can have consequences for gynecologic and obstetric
      patients and fetuses. Amenorrhea, infertility, hyperemesis gravidarum, and
      preterm birth have been linked to eating disorders (EDs). This study aimed to
      evaluate obstetrician-gynecologists' ED-related knowledge, attitudes, and
      practices. METHODS: Questionnaires were sent to 968 Fellows of the American
      College of Obstetricians and Gynecologists between November 2007 and March 2008.
      Data were analyzed separately for generalists (provide obstetric and gynecologic
      care) and gynecologists only (treat only gynecologic patients). RESULTS: A
      majority of obstetrician-gynecologists assess body weight, exercise, body mass
      index, and dieting habits. Less than half assess ED history, body image concerns,
      weight-related cosmetic surgery, binging, and purging. Over half (54%) of
      generalists believed ED assessment falls within their purview. Most (90.8%)
      generalists agreed or strongly agreed that EDs can negatively impact pregnancy
      outcome. A majority rated residency training in diagnosing (88.5%) and treating
      (96.2%) EDs as barely adequate or less. Most knew low birth weight (91%) and
      postpartum depression (90%) are associated with maternal EDs, though over a third
      was unsure about several consequences. Some gender differences emerged; females
      screen for more ED indicators and are more likely to view ED assessment as within
      their role. CONCLUSIONS: Despite the consequences of EDs and the fact that most
      physicians agree EDs can negatively impact pregnancy, only about half view ED
      assessment as their responsibility. Only some weight- and diet-related topics are
      assessed, and there are gaps in knowledge of ED consequences. Obstetrician
      gynecologists are not confident in their training regarding EDs. Improvement in
      knowledge and altering obstetrician-gynecologists' view of their responsibilities
      may improve ED screening rates.

PMID- 19743911
TI  - Use of the VS-sense swab in diagnosing vulvovaginitis.
AB  - BACKGROUND: Although pH assessment of vaginal secretions is beneficial for
      diagnosing vaginitis, it is not commonly done. The purpose of this study was to
      determine the performance characteristics of the VS-Sense (pH test) swab (Common
      Sense, Ltd., Caesarea, Israel) in augmenting the diagnosis of vaginitis. METHODS:
      We prospectively studied 193 women with acute vulvovaginal symptoms and 74
      asymptomatic controls at three medical centers. The VS-Sense swab was
      administered intravaginally, and results were interpreted by a nurse. These
      results were compared with final clinical and laboratory diagnoses. RESULTS: In
      women with an elevated pH caused by bacterial vaginosis (BV), trichomonas, and
      other types of vaginitis, the VS-Sense test sensitivity and specificity were
      82.3% (102 of 124) (95% CI 74.4%-88.5%) and 94.2% (129 of 137) (95% CI 88.8%
      97.4%), respectively. There was an 86.2% (95% CI 81.3%-90.1%) overall agreement
      between pH paper and VS-Sense swab results. CONCLUSIONS: The VS-Sense test offers
      an alternative approach to measuring vaginal pH with nitrazine paper. Use of this
      simple, more rapid test may facilitate the diagnosis of vulvovaginitis.

PMID- 19743913
TI  - Role of adhesion in arthropod immune recognition.
AB  - The recognition and inactivation of toxins and pathogens are mediated by a
      combination of cell-free and cellular mechanisms. A number of soluble and
      membrane-bound pattern recognition molecules interact with elicitors to become
      involved in both cell-free inactivation as well as cellular uptake reactions.
      Here we describe the possible recognition and effector function of key arthropod
      immune proteins, such as peroxinectin, hemolin, and hemomucin, as an outcome of
      changes in adhesiveness, which drive self-assembly reactions leading to cell-free
      coagulation and cellular uptake reactions. The fact that some of these proteins
      are essential for immune and developmental functions in some species, but are not
      found in closely related species, may point to the existence of multiprotein
      assemblies, which are conserved at the mechanistic level and can function with
      more than one combination of protein constituents.

PMID- 19743914
TI  - Physical ecology of fluid flow sensing in arthropods.
AB  - Terrestrial and aquatic arthropods sense fluid flow in many behavioral and
      ecological contexts, using dedicated, highly sensitive mechanosensory hairs,
      which are often abundant. Strong similarities exist in the biomechanics of flow
      sensors and in the sensory ecology of insects, arachnids, and crustaceans in
      their respective fluid environments. We extend these considerations to flow in
      sand and its implications for flow sensing by arthropods inhabiting this granular
      medium. Finally, we highlight the need to merge the various findings of studies
      that have focused on different arthropods in different fluids. This could be
      achieved using the unique combination, for sensory ecology, of both a workable
      and well-accepted mathematical model for hair-based flow sensing, both in air and
      water, and microelectronic mechanical systems microtechnology to tinker with
      physical models.

PMID- 19743915
TI  - Threats posed to rare or endangered insects by invasions of nonnative species.
AB  - Endangerment factors are reviewed for 57 U.S. federally listed insects and 116
      rare eastern North American lepidopterans to determine the importance of invasive
      species relative to 15 other recognized endangerment factors. Invasive plants,
      social insects (especially ants), and vertebrate grazers and predators repeatedly
      were identified as groups directly or indirectly threatening native insect
      biodiversity. Among rare eastern North American lepidopterans, the (mostly
      indirect) consequences of the establishment of the gypsy moth (Lymantria dispar)
      surfaced as a general threat. Remote islands, especially those with high human
      visitation, stand out as being highly threatened by invasives. In the worst
      cases, impacts from invasive species cascade through a community and destabilize
      existing trophic interconnections and alter basic ecosystem properties, changing
      hydrology, nutrient cycles, soil chemistry, fire susceptibility, and light
      availability, and precipitate myriad other changes in biotic and abiotic
      parameters. Invasive ants and herbivorous insects provide some of the most
      dramatic examples of such insect-induced invasional cascades.

PMID- 19743916
TI  - Managing invasive populations of Asian longhorned beetle and citrus longhorned
      beetle: a worldwide perspective.
AB  - The Asian longhorned beetle (ALB), Anoplophora glabripennis (Motschulsky), and
      citrus longhorned beetle (CLB), Anoplophora chinensis (Forster) (Coleoptera:
      Cerambycidae), are polyphagous xylophages native to Asia and are capable of
      killing healthy trees. ALB outbreaks began in China in the 1980s, following major
      reforestation programs that used ALB-susceptible tree species. No regional CLB
      outbreaks have been reported in Asia. ALB was first intercepted in international
      trade in 1992, mostly in wood packaging material; CLB was first intercepted in
      1980, mostly in live plants. ALB is now established in North America, and both
      species are established in Europe. After each infestation was discovered,
      quarantines and eradication programs were initiated to protect high-risk tree
      genera such as Acer, Aesculus, Betula, Populus, Salix, and Ulmus. We discuss
      taxonomy, diagnostics, native range, bionomics, damage, host plants, pest status
      in their native range, invasion history and management, recent research, and
      international efforts to prevent new introductions.

PMID- 19743917
TI  - Protein carbonylation.

PMID- 19743919
TI  - Adenosine triphosphate depletion of erythrocytes simulates the phenotype
      associated with pyruvate kinase deficiency and confers protection against
      Plasmodium falciparum in vitro.
AB  - BACKGROUND: Erythrocytes from individuals with pyruvate kinase deficiency (PKD)
      are resistant to invasion by Plasmodium falciparum parasites, and erythrocytes
      infected with ring-stage parasites are preferentially cleared by macrophages in
      vitro. However, the underlying molecular basis of protection is unknown. In the
      present study, we examined adenosine triphosphate (ATP) levels in PKD
      erythrocytes (ie, erythrocytes from individuals with PKD) and determined whether
      depletion of ATP in normal erythrocytes would recapitulate the phenotype observed
      with PKD. METHODS: We examined ATP levels in homozygous PKLR(-/-) and
      heterozygous PKLR(+/-) human erythrocytes and used sodium fluoride treatment to
      inhibit ATP generation in normal human erythrocytes. RESULTS: We demonstrated
      that ATP levels are reduced in PKLR(-/-) (percentage of control erythrocytes,
      26%; interquartile range [IQR], 21%-48%) and PKLR(+/-) erythrocytes (percentage
      of control erythrocytes, 64%; IQR, 60%-73%) and that there is a correlation
      between ATP levels in erythrocytes and both inhibition of parasite invasion and
      enhancement of phagocytosis of erythrocytes infected with ring-stage parasites.
      Analysis of ATP distribution in parasitized erythrocytes demonstrated that
      parasites invading PKD erythrocytes respond to low intraerythrocytic ATP levels
      by means of a parallel increase in parasite-derived ATP via up-regulation of P.
      falciparum-specific pyruvate kinase. CONCLUSION: These data suggest that reduced
      erythrocyte ATP levels may contribute to the protection displayed by PKD
      erythrocytes in vitro and may provide a model system with which to define the
      molecular basis of protection in inherited PKD.

PMID- 19743920
TI  - CXC chemokine-mediated protection against visceral leishmaniasis: involvement of
      the proinflammatory response.
AB  - Visceral leishmaniasis, caused by the protozoan parasite Leishmania donovani, is
      characterized by the loss of ability of the host to generate an effective immune
      response. In the present study, the comparative potential of CXC chemokines,
      interferon-gamma-inducible protein-10 (IP-10) and interleukin-8 (IL-8) in
      restricting Leishmania donovani infection via the release of nitric oxide and
      proinflammatory cytokines was studied in an in vitro model. Nitric oxide, a
      crucial mediator for IP-10-mediated leishmanicidal activity, was found to be
      dependent on inducible nitric oxide synthase 2 (iNOS2) expression and was linked
      to the mitogen-activated protein kinases (MAPK) signaling pathway. Further, IP-10
      was also able to abrogate the survival of Leishmania in an in vivo model of
      visceral leishmaniasis by restoration of Th1 cytokines and nitric oxide. Thus,
      this study strongly demonstrates that IP-10, like CC chemokines, is involved in
      rendering a protective response in visceral leishmaniasis via up-regulation of
      proinflammatory mediators.

PMID- 19743921
TI  - Recent human influenza A/H3N2 virus evolution driven by novel selection factors
      in addition to antigenic drift.
AB  - BACKGROUND: Examination of the evolutionary dynamics of complete influenza viral
      genomes reveals that other processes, in conjunction with antigenic drift, play
      important roles in viral evolution and selection, but there is little biological
      evidence to support these genomic data. Previous work demonstrated that after the
      A/Fujian/411/2002-like H3N2 influenza A epidemic during 2003-2004, a preexisting
      nondominant Fujian-like viral clade gained a small number of changes in genes
      encoding the viral polymerase complex, along with several changes in the
      antigenic regions of hemagglutinin, and in a genome-wide selective sweep, it
      replaced other co-circulating H3N2 clades. METHODS: Representative strains of
      these virus clades were evaluated in vitro and in vivo. RESULTS: The newly
      dominant 2004-2005 A/California/7/2004-like H3N2 clade, which featured 2 key
      amino acid changes in the polymerase PA segment, grew to higher titers in MDCK
      cells and ferret tissues and caused more-severe disease in ferrets. The
      polymerase complex of this virus demonstrated enhanced activity in vitro,
      correlating directly to the enhanced replicative fitness and virulence in vivo.
      CONCLUSION: These data suggest that influenza strains can be selected in humans
      through mutations that increase replicative fitness and virulence, in addition to
      the well-characterized antigenic changes in the surface glycoproteins.

PMID- 19743922
TI  - Comparative study between serological and molecular methods for diagnosis of
      toxoplasmosis in women and small ruminants in Egypt.
AB  - Routine serological diagnosis of toxoplasmosis provides high sensitivity, but
      specificity varies depending on the test used; false-positive results (IgM) have
      been reported. Blood samples were collected from 88 women (59 pregnant and 29
      nonpregnant) and 86 contact animals (62 sheep and 24 goats) at El Fayoum
      Governorate during the period from October 2005 to December 2006. All collected
      samples were tested for Toxoplasma gondii infection by serological tests (ELISA
      IgM & IgG and Sabin-Feldman dye test) and polymerase chain reaction (PCR).
      Results revealed specific IgG in 45.8% and 41.4%, IgM in 30.5% and 24.2%, and
      positive Sabin-Feldman dye test in 23.7% and 17.2% in pregnant and nonpregnant
      women, respectively. Positive PCR products were detected in 32.2% and 27.6% in
      pregnant and nonpregnant women, respectively. Regarding animals, positive ELISA
      IgG and PCR were detected in 98.4% and 67.7% of sheep and 41.7% and 25.0% of
      goats, respectively. It was concluded that serological tests can detect higher
      rate of toxoplasmosis than PCR, so ELISA combined with the PCR technique is a
      recommended tool for accurate diagnosis of toxoplasmosis.

PMID- 19743923
TI  - A comparison of polymerase chain reaction and international organization for
      standardization methods for determination of Enterobacter sakazakii contamination
      of infant formulas from Chinese mainland markets.
AB  - Enterobacter sakazakii is an emerging foodborne pathogen associated with
      meningitis, necrotizing enterocolitis, and sepsis in infants. One of the main
      transmission vehicles is the commercially available infant formulas. To provide
      efficient options and direction for detecting E. sakazakii in infant formulas,
      evaluation of different polymerase chain reaction (PCR) assays targeting the 16S
      23S rDNA internal transcribed spacer (ITS), the ompA gene, and the alpha-1,4
      glucosidase gene (gluA) of this organism, were compared to the International
      Organization for Standardization (ISO) method for detecting E. sakazakii in the
      243 commercial infant formula samples. Twelve samples were found to be positive
      for E. sakazakii by all the PCR assays used, followed by sequencing of PCR
      products. Ten samples were found to be positive by the ISO method, and all 10
      gave positive signals for all the PCR amplifications. In contrast, four false
      positive results were generated by single-PCR of the ITS region and one false
      positive result targeting the ompA gene, while two false-negative results
      occurred with the ISO method. Combined with selective enrichment step(s), duplex
      PCR targeting ITS and ompA and targeting ompA and gluA genes or single-PCR of the
      gluA gene can be used to test for contamination by E. sakazakii in infant
      formulas before they enter the market. PCR techniques will be helpful for routine
      monitoring and risk assessment for large-scale screenings.

PMID- 19743924
TI  - Molecular characterization of temporally and geographically matched Streptococcus
      agalactiae strains isolated from food products and bloodstream infections.
AB  - In a defined geographic area, during a 3-month period, 914 food products were
      screened for Streptococcus agalactiae, and S. agalactiae strains isolated from
      bloodstream infections (BSI) in nonpregnant adults were collected. Eleven S.
      agalactiae strains were isolated from 1.2% of food products, with high rates in
      pastries (7.0%) and seafood products (11.8%). These findings indicate that S.
      agalactiae is a food product contaminant. Seven S. agalactiae BSI were observed
      in nonpregnant adults representing an incidence of 0.015/100 admissions. The
      distribution of strains in serotypes did not differ according to origin of the
      strains; food products and clinical strains were of serotypes Ia (22%), Ib (11%),
      II (5%), III (22%), IV (5%), and V (33%). The strains isolated from seafoods were
      of serotypes Ia and Ib. The distribution of strains in Sequence Types differed
      according to their origin; food strains were equally distributed between the
      major clonal complex (CC), CC1 (27%), CC9 (18%), CC17 (18%), and CC23 (27%),
      whereas a high proportion of BSI strains belonged to CC1 (57%). DNA
      macrorestriction using SmaI revealed diversity; nine different patterns were
      found for the 11 food strains and seven for the 7 BSI strains. One pattern was
      similar for two food strains and one BSI strain. On account of the molecular
      characteristics previously described for S. agalactiae strains of human carriage
      and fish and mice infections, the serotype characteristics of seafood strains
      suggest contamination by aquatic S. agalactiae, whereas the molecular
      characteristics of strains from pastries suggest human contamination, but may
      also originate from rodents. Indeed, serotype V CC1 strains, found in food and
      responsible for a high percentage of BSI in nonpregnant adults, belong to a known
      clone spreading worldwide, and have also been described in mice.

PMID- 19743925
TI  - Genetic and phenotypic characterization of the bla(CMY) gene from Escherichia
      coli and Salmonella enterica isolated from food-producing animals, humans, the
      environment, and retail meat.
AB  - The bla(CMY-2) family of the ampC beta-lactamase genes confer broad-spectrum
      resistance to beta-lactam antimicrobials, including ceftriaxone and ceftiofur, as
      well as to beta-lactamase inhibitors, such as clavulanic acid. Organisms with the
      bla(CMY-2) phenotype have been recovered from the environment and from retail
      meat products, posing a potential public health risk. The objectives of this
      study were to sequence the bla(CMY-2) gene from Escherichia coli and Salmonella
      enterica from multiple sources that had a reduced susceptibility to ceftriaxone
      and to determine the effect of observed mutations in the bla(CMY-2) gene on the
      antimicrobial resistance phenotype (spectrum and minimum inhibitory
      concentration/susceptibility patterns) of the isolates. The bla(CMY-2) genes from
      52 bacterial isolates were sequenced for this study. Sixty-two percent (32/52)
      were E. coli and 38% (20/52) were S. enterica. Of the 32 E. coli isolates, 30
      were found to carry a beta-lactamase gene that was 100% homologous to bla(CMY-2).
      One of the E. coli isolates was found to contain a gene that was 90% homologous
      to bla(CMY-2). This isolate also had lower minimum inhibitory concentrations to
      tetracyclines, streptomycin, and the sulfonamide antimicrobials than are commonly
      expected for isolates containing the bla(CMY-2). Of the 20 genes obtained from
      Salmonella isolates, 8 (40%) were found to be homologous to bla(CMY-2), with no
      altered susceptibility phenotypes observed.

PMID- 19743926
TI  - Conjugative transferability of the A/C plasmids from Salmonella enterica isolates
      that possess or lack bla(CMY) in the A/C plasmid backbone.
AB  - The objective of this study was to understand the conjugative transmissibility of
      resistance plasmids present in 205 Salmonella enterica isolates from bovine
      sources. Polymerase chain reaction (PCR)-based replicon typing was used to type
      plasmid replicons. Conjugation experiments were preformed in triplicate at 30
      degrees C and 37 degrees C on solid medium. PCR mapping of the A/C transfer gene
      operon was done on 17 Salmonella Newport isolates that were only positive for
      A/C. Eighty-six percent (n = 177) of the Salmonella isolates were multidrug
      resistant (MDR) with resistance to 3-12 antimicrobial agents. Of these, 82% (n =
      146) were resistant to extended-spectrum cephalosporins and possessed a bla(CMY)
      gene. A/C was the predominant replicon detected, present in 90% (n = 160) of the
      MDR isolates. Twenty-three percent (n = 37) of the A/C-positive strains were
      positive for a second replicon. Replicons coresident with A/C included I1, N,
      B/O, HI1, and HI2. Only 31% (n = 54) of the MDR isolates produced
      transconjugants, and most of these donors carried multiple replicons. A/C
      cotransferred with B/O, N, and I1 at both 30 degrees C and 37 degrees C and with
      HI2 at 30 degrees C. Seven Salmonella Newport isolates that produced
      transconjugants possessed only the single A/C replicon and lacked bla(CMY). PCR
      mapping of the A/C transfer gene operon in ten Salmonella Newport isolates that
      carried bla(CMY) revealed a bla(CMY) inverted repeat element integrated between
      the traA and traC genes. These results suggest that A/C may have been a
      conjugative plasmid before the integration of bla(CMY) into the transfer gene
      operon. Additionally, transfer deficient A/C replicons may be mobilized in the
      presence of certain compatible conjugative plasmids.

PMID- 19743927
TI  - Quantification of mutated alleles of 23S rRNA in macrolide-resistant
      Campylobacter by TaqMan real-time polymerase chain reaction.
AB  - A quantitative detection of mutations mediating high-level macrolide resistance
      in Campylobacter is necessary for molecular epidemiological investigation and
      research. In this study, a new TaqMan probe-based real-time polymerase chain
      reaction method, with high specificity and sensitivity, was firstly established
      to identify and quantify mutated alleles associated with macrolide resistance
      (A2074C and A2075G) in 23S rDNA of Campylobacter. Three standard plasmids
      (plasmid wild type, plasmid containing A2074C, and plasmid containing A2075G)
      were constructed to evaluate the specificity of the established TaqMan real-time
      polymerase chain reaction and to generate standard curve for absolute
      quantification. This assay, using specific probes, can particularly identify the
      three standard plasmids corresponding to three genotypes (wild type, A2074C
      tranversion, and A2075G transition). The linear detection range of mutated
      alleles was found between 10 and 10(6) copies with the correlation coefficient of
      0.99. Twelve laboratory-induced macrolide-resistant derivations and 18 isolated
      Campylobacter strains were also tested to evaluate the accuracy of the new assay.
      The specificity and accuracy of our established method were 100% identical to DNA
      sequencing. The entire procedure of the assay takes less than 2 h, eliminating
      the need for gel electrophoresis. Compared with previously reported qualitative
      methods, this quantitative genetic assay is a rapid and sensitive and accurate
      method for analysis of mutated alleles in 23S rDNA associated with high-level
      macrolide resistance in Campylobacter.

PMID- 19743928
TI  - Characterization of clinical and environmental types of Vibrio vulnificus
      isolates from Louisiana oysters.
AB  - Vibrio vulnificus, a naturally occurring estuarine bacterium frequently
      transmitted to humans via raw oysters, is a leading cause of seafood-related
      deaths in the United States. Although unique virulence markers have not been
      identified to date, multiple biomarkers have been used previously to associate
      strains with clinical or environmental types of V. vulnificus. In this study, we
      evaluated the usefulness of these biomarkers in characterizing 349 V. vulnificus
      oyster isolates by the presence/absence of a viuB-associated fragment and
      genotypes of three biomarkers: the virulence-correlated gene (vcg), 16S rRNA, and
      the capsular polysaccharide (CPS) operon. Genotyping data indicated that
      environmental-type V. vulnificus strains accounted for the majority of oyster
      isolates, and the percentages ranged from 51.6% for 16S rRNA (type A) to 72.5%
      for CPS (allele 2 or none). There was also a small percentage (8%) of V.
      vulnificus isolates possessing both environmental (type A) and clinical (type B)
      genotypes of 16S rRNA. Additionally, the presence of the viuB fragment (41%) was
      significantly associated with clinical genotypes of V. vulnificus (p < 0.0001).
      An interesting seasonal pattern was observed, with clinical-type V. vulnificus
      isolates more frequently associated with warmer months. In conclusion, the
      majority of V. vulnificus isolates present in Louisiana raw oysters were of
      environmental type. There existed a seasonal variation in the V. vulnificus
      genotypes identified, which may help guide future control measures to focus more
      specifically on seasons that tend to accumulate more clinical-type V. vulnificus.
      The study also highlighted the need to identify unique virulence markers in this
      organism, which could facilitate future screening of virulent V. vulnificus
      strains from oysters.

PMID- 19743929
TI  - Bond strength of an etch-and-rinse adhesive to KrF excimer laser-treated dentin.
AB  - OBJECTIVE: The aim of this work was to evaluate the effect of KrF excimer laser
      treatment on the bond strength between dentin and an etch-and-rinse adhesive
      system. MATERIALS AND METHODS: Polished dentin surfaces were subjected to the
      following treatments: (1) 35% phosphoric acid etching for 15 s; (2) laser surface
      treatment using KrF excimer laser radiation (1 J/cm(2)); and (3) laser treatment
      under the same conditions followed by acid etching. After treating the dentin, an
      etch-and-rinse adhesive (Adper Scotchbond 1 XT, 3M ESPE) was applied and
      composite (Esthet-X, Dentsply Caulk, Konstanz, Germany) build-ups were
      incrementally constructed. After 24 h of water storage at 37 degrees C, 1 mm(2)
      beams were longitudinally cut from the samples. Microtensile sticks were loaded
      in tension at a crosshead speed of 0.5 mm/min. Bond strength data were analyzed
      with one-way ANOVA and the Student-Newman-Keuls test (p < 0.05). The dentin
      surfaces resulting from each surface treatment and the fracture surfaces
      originated by the bond-strength tests were observed under a scanning electron
      microscope. RESULTS: Laser-treated surfaces exhibited a cone-shaped topography
      with a frank occlusion of dentinal tubules, while acid etching produced a
      smoother surface with open tubules. Application of 35% phosphoric acid on laser
      treated dentin surfaces resulted in the partial dissolution of the surface cones.
      Mean microtensile bond strengths for acid-etched dentin was significantly higher
      (33.7 +/- 8.7 MPa) than for laser-treated (13.8 +/- 5.1 MPa) and laser-treated
      and etched surfaces (19.7 +/- 6.9 MPa). A higher percentage of cohesive failures
      at the base of the cones occurred in the laser-treated group, whereas mixed
      failures were predominant on acid-etched samples. CONCLUSION: The cone-shaped
      texture produced by treating dentin with KrF laser radiation does not improve the
      bond strength of the tested etch-and rinse adhesive system when compared to the
      traditional acid-etching technique.

PMID- 19743930
TI  - Helium-neon laser reduces the inflammatory process of arthritis.
AB  - OBJECTIVE: A histological study of the anti-inflammatory effect of helium-neon
      laser in models of arthropathies induced by hydroxyapatite and calcium
      pyrophosphate in rats. BACKGROUND: Crystal deposition diseases are inflammatory
      pathologies induced by cellular reaction to the deposit of crystals in the
      joints. METHODS: Fifty-six Suquia strain rats were distributed in seven groups.
      Two mg of each crystal diluted in 0.05 ml physiologic solution were injected six
      times in each back limb joint, during two weeks on alternate days. Eight J/cm(2)
      were applied daily to the crystal-injected joints on five consecutive days. The
      joints were cut and put in 10% formaldehyde, stained with hematoxylin-eosin and
      observed by light microscopy. The percentage of area with inflammatory
      infiltrates was determined in five optical microscopy photographs (100X) for each
      group and analyzed using the Axionvision 4.6 program. A Pearson's Chi Squared
      test was applied, with significance level set at p < 0.05. RESULTS: Both crystals
      produced an inflammatory process in the osteoarticular structures, consisting of
      predominantly mononuclear infiltration, fibrosis, and granulomas of foreign body
      type giant cells containing phagocytosed remains of crystals. In the arthritic
      joints treated with laser, a marked decrease (p < 0.0001) was found in the
      percentage of area with inflammatory infiltrates, although the granulomas
      remained in a less ostensible form, with adipose tissue cells, fibrosis bands
      with light residual inflammation, and an absence of or very few crystals. Laser
      alone or physiologic solution injection did not produce histological changes.
      CONCLUSIONS: Helium-neon laser reduced the intensity of the inflammatory process
      in the arthritis model induced by hydroxyapatite and calcium pyrophosphate
      crystals.

PMID- 19743936
TI  - Fungal chitin-glucan scaffold for managing diabetic xerosis of the feet in
      menopausal women.
AB  - BACKGROUND: Corneocyte accumulation (hyperkeratosis, xerosis) commonly occurs in
      the stratum corneum (SC) of the feet of diabetic patients, as well as menopausal
      women. OBJECTIVE: To compare the effects of a 2.5% chitin-glucan formulation with
      its placebo, and commercially available glycerol formulations. METHODS: This two
      step controlled double-blind, randomized, intra-individual study was performed in
      30 type 1 and 2 diabetic menopausal women suffering from xerosis of the feet. The
      formulations were applied once daily for 3 weeks. Electrometric assessments were
      performed on three sites of the feet at entry in the study, at weekly intervals
      during the treatment phase, and in a 2-week follow-up out of treatment. Positive
      controls consisted in two commercially available formulations enriched in
      glycerol. RESULTS: Data revealed an unequivocal benefit provided by the 2.5%
      chitin-glucan formulation compared with placebo. The electrometric values were
      significantly higher at each evaluation time during both treatment and follow-up
      phases. The two glycerol-enriched formulations showed slightly different kinetics
      of SC moisturization. A steep increase was followed by a plateau level and a
      rapid decline after stopping the treatments. CONCLUSION: The increased
      moisturization of the SC of the sole probably improves the desquamation process
      and reduces xerosis of the soles.

PMID- 19743937
TI  - Trabectedin: an anticancer drug from the sea.
AB  - BACKGROUND: Trabectedin (ET-743) is an anticancer agent originally isolated from
      Ecteinascidia turbinata, a marine organism. OBJECTIVE: The goal of this review is
      to describe the chemical characteristics, mechanism of action and the results of
      clinical trials with this compound. The toxicities are described, as well as the
      pharmacokinetics. The regulatory affairs and marketing strategies for this
      compound are also discussed. METHODS: Medline and meeting proceedings were
      searched to accomplish our objectives. RESULTS/CONCLUSIONS: Trabectedin is a
      unique alkylating agent. It affects a variety of transcription factors, cell
      proliferation, and nucleotide excision repair mechanism. In addition, it inhibits
      the MDR-1 gene, which is responsible for the resistance of cancer cells to
      chemotherapeutic agents. The main toxicities of this agent are transaminitis and
      myelosuppression, both reversible and noncumulative. At present, trabectedin is
      approved in Europe for the treatment of sarcoma. The combination of this compound
      with other chemotherapeutics has been tested in Phase I studies in sarcomas and
      is feasible. This drug in combination with doxil has shown to improve outcome in
      relapsed ovarian cancer, compared with doxil alone. The results of this study may
      lead to an FDA approval of the combination in the USA, for the treatment of
      relapsed ovarian cancer.

PMID- 19743938
TI  - Pharmacotherapy of hyperglycemia.
AB  - Type 2 diabetes mellitus (T2DM) is a chronic, progressive disorder that affects
      more than 230 million people worldwide and is expected to affect 366 million by
      2030. Both the prevalence of T2DM and the cost of its long term complications has
      driven the focus and emphasis on treatments aimed at reducing hyperglycemia and
      controlling hypertension and dyslipidemia. In the last 5 years new glucose
      lowering drugs acting on novel pathways have been developed, licensed and
      launched. These drugs include the glucagon-like peptide (GLP-1) agonists,
      exenatide, and dipeptidyl peptidase (DPP-IV) inhibitors such as sitagliptin and
      saxagliptin. This review describes current approaches to T2DM treatment, focusing
      on newer agents which tend to be associated with less hypoglycemia and possible
      weight loss, and addresses the potential roles of novel oral pharmacologic agents
      in the late-stages of development that might provide new options for the
      management of this disease.

PMID- 19743939
TI  - Enzyme therapy for the treatment of type 1 Gaucher disease: clinical outcomes and
      dose - response relationships.
AB  - BACKGROUND: Enzyme therapy for Gaucher disease has improved the lives of many
      patients, by reducing the burden of their disease. Several studies have sought to
      determine to what extent optimal clinical outcomes are a function of the
      prescribed enzyme dose and its resultant costs. OBJECTIVE: Issues concerning dose
      - response relationships during initial and maintenance treatment phases and
      currently applied treatment goals have been addressed. METHODS: All studies that
      aimed to describe the efficacy of different doses of treatment and approaches for
      maintenance, such as lowering the dose or changing to less frequent infusions and
      the effects of drug interruptions, were reviewed. RESULTS/CONCLUSION: Dose -
      response relationships do exist, but doses between 30 and 60 U/kg per month may
      be sufficient in a large majority of patients. Goals of treatment should include
      important clinical end points, such as enhanced quality of life and decreased
      risk for malignancies and other morbidities. The relationship between these
      important end points and treatment schedules deserve further study.

PMID- 19743940
TI  - Is liraglutide or exenatide better in type 2 diabetes?

PMID- 19743941
TI  - Besifloxacin, a new ophthalmic fluoroquinolone for the treatment of bacterial
      conjunctivitis.
AB  - Besifloxacin is a new fluoroquinolone anti-infective developed for ophthalmic
      use. Besifloxacin ophthalmic suspension 0.6% (Besivance) was recently approved
      for the treatment of bacterial conjunctivitis. The objective of this article is
      to provide a comprehensive overview of microbiological,
      pharmacokinetic/pharmacodynamic and clinical studies with besifloxacin.
      Microbiological studies have demonstrated that besifloxacin has wide-spectrum and
      potent activity against common ocular pathogens, including Gram-negative and Gram
      positive pathogens associated with bacterial conjunctivitis, and retained
      activity against fluoroquinolone-resistant staphylococci and multidrug-resistant
      strains. In preclinical and human studies, topically applied besifloxacin had a
      prolonged ocular concentration and minimal systemic exposure. In clinical
      studies, patients randomized to besifloxacin ophthalmic suspension 0.6%
      experienced significantly higher rates of clinical resolution and microbial
      eradication than patients randomized to vehicle. Besifloxacin ophthalmic
      suspension 0.6% was also found to be as effective and well tolerated as
      moxifloxacin ophthalmic solution 0.5%. The low minimum inhibitory concentrations
      and high attainment of pharmacodynamic targets with besifloxacin may contribute
      to a lower risk for the emergence of bacterial resistance, although further
      studies are needed. These data indicate that besifloxacin ophthalmic suspension
      0.6% is an important new option for the treatment of bacterial conjunctivitis.

PMID- 19743942
TI  - Cost-utility of celecoxib use in different treatment strategies for
      osteoarthritis and rheumatoid arthritis from the Quebec healthcare system
      perspective.
AB  - OBJECTIVE: To assess the cost-utility of celecoxib in three treatment strategies
      for arthritis in Quebec, considering both upper gastrointestinal (GI) and
      cardiovascular (CV) events. METHODS: A Markov analytic framework was used to
      model patients with osteoarthritis and rheumatoid arthritis at low/average and
      high risk of GI and CV toxicity over 5 years with monthly cycles. Treatment
      strategies were modelled in line with Canadian clinical practice. In first-line
      treatment, patients started on celecoxib; second-line, patients started on a non
      selective non-steroidal anti-inflammatory drug (NSAID) and switched to celecoxib
      after a first GI event; third-line, patients started on a non-selective NSAID,
      added a proton pump inhibitor (PPI) after a first GI event, and switched to
      celecoxib after a second GI event (while maintaining the PPI). Model inputs were
      determined through comprehensive literature searches (MEDLINE and EMBASE) from
      1995 to 2006. Included studies evaluated GI (dyspepsia, uncomplicated and
      complicated ulcers, death) and CV (myocardial infarction, stroke, death) events.
      Drug and procedure costs were derived from Canadian published sources (Can$2005).
      RESULTS: Total costs per patient for celecoxib first-, second-, and third-line
      treatment were Can$4,790, $3,390, and $3,466, and total quality-adjusted life
      years (QALY) were 3.251, 3.231, and 3.230, respectively. In all risk categories,
      celecoxib second-line was less costly and as effective as celecoxib third-line,
      producing savings to the healthcare system. Although celecoxib first-line
      generated incremental expenditures versus celecoxib second-line, it was also more
      effective. The resulting cost-utility ratio for the high-risk population was
      Can$54,696/QALY. Based on this analytical approach, a treatment strategy where
      celecoxib is used before the combination of a non-selective NSAID plus a PPI
      possesses cost advantages for the Quebec provincial drug programme. One-way
      sensitivity analysis (varying GI and CV event rates, utilities, and cost)
      generally showed second-line treatment with celecoxib as the dominant strategy
      compared with third-line treatment with celecoxib. CONCLUSION: Although
      effectiveness of second- and third-line celecoxib use is similar, total cost is
      lower for second-line. These results suggest that the use of celecoxib before the
      combination of a non-selective NSAID plus a PPI is relatively cost-effective in
      the treatment of arthritis pain and support the full benefit listing of celecoxib
      in Quebec's drug programme.

PMID- 19743943
TI  - Health effects of inhaled engineered and incidental nanoparticles.
AB  - Engineered nanoscale materials provide tremendous promise for technological
      advancements; however, concerns have been raised about whether research of the
      possible health risks of these nanomaterials is keeping pace with products going
      to market. Research on nanomaterials, including carbon nanotubes, semiconductor
      crystals, and other ultrafine particles (i.e., titanium dioxide, quantum dots,
      iridium) will be examined to illustrate what is currently known or unknown about
      how particle characteristics (e.g., size, agglomeration, morphology, solubility,
      surface chemistry) and exposure/dose metrics (e.g., mass, size, surface area)
      influence the biological fate and toxicity of inhaled nanosized particles. The
      fact that nanosized particles (1) have a potentially high efficiency for
      deposition; (2) target both the upper and lower regions of the respiratory tract;
      (3) are retained in the lungs for a long period of time, and (4) induce more
      oxidative stress and cause greater inflammatory effects than their fine-sized
      equivalents suggest a need to study the impact of these particles on the body.
      Achieving a better understanding of the dynamics at play between particle
      physicochemistry, transport patterns, and cellular responses in the lungs and
      other organs will provide a future basis for establishing predictive measures of
      toxicity or biocompatibility and a framework for assessing potential human health
      risks.

PMID- 19743944
TI  - Creating context for the use of DNA adduct data in cancer risk assessment: I.
      Data organization.
AB  - The assessment of human cancer risk from chemical exposure requires the
      integration of diverse types of data. Such data involve effects at the cell and
      tissue levels. This report focuses on the specific utility of one type of data,
      namely DNA adducts. Emphasis is placed on the appreciation that such DNA adduct
      data cannot be used in isolation in the risk assessment process but must be used
      in an integrated fashion with other information. As emerging technologies provide
      even more sensitive quantitative measurements of DNA adducts, integration that
      establishes links between DNA adducts and accepted outcome measures becomes
      critical for risk assessment. The present report proposes an organizational
      approach for the assessment of DNA adduct data (e.g., type of adduct, frequency,
      persistence, type of repair process) in concert with other relevant data, such as
      dosimetry, toxicity, mutagenicity, genotoxicity, and tumor incidence, to inform
      characterization of the mode of action. DNA adducts are considered biomarkers of
      exposure, whereas gene mutations and chromosomal alterations are often biomarkers
      of early biological effects and also can be bioindicators of the carcinogenic
      process.

PMID- 19743945
TI  - Creating context for the use of DNA adduct data in cancer risk assessment: II.
      Overview of methods of identification and quantitation of DNA damage.
AB  - The formation of deoxyribonucleic acid (DNA) adducts can have important and
      adverse consequences for cellular and whole organism function. Available methods
      for identification of DNA damage and quantification of adducts are reviewed.
      Analyses can be performed on various samples including tissues, isolated cells,
      and intact or hydrolyzed (digested) DNA from a variety of biological samples of
      interest for monitoring in humans. Sensitivity and specificity are considered key
      factors for selecting the type of method for assessing DNA perturbation. The
      amount of DNA needed for analysis is dependent upon the method and ranges widely,
      from <1 microg to 3 mg. The methods discussed include the Comet assay, the
      ligation-mediated polymerase reaction, histochemical and immunologic methods,
      radiolabeled ((14)C- and (3)H-) binding, (32)P-postlabeling, and methods
      dependent on gas chromatography (GC) or high-performance liquid chromatography
      (HPLC) with detection by electron capture, electrochemical detection, single or
      tandem mass spectrometry, or accelerator mass spectrometry. Sensitivity is
      ranked, and ranges from approximately 1 adduct in 10(4) to 10(12) nucleotides. A
      brief overview of oxidatively generated DNA damage is also presented. Assay
      limitations are discussed along with issues that may have impact on the
      reliability of results, such as sample collection, processing, and storage.
      Although certain methodologies are mature, improving technology will continue to
      enhance the specificity and sensitivity of adduct analysis. Because limited
      guidance and recommendations exist for adduct analysis, this effort supports the
      HESI Committee goal of developing a framework for use of DNA adduct data in risk
      assessment.

PMID- 19743946
TI  - Chemically induced pheochromocytomas in rats: mechanisms and relevance for human
      risk assessment.
AB  - Pheochromocytomas are tumors originating from chromaffin cells of the adrenal
      medulla, which have been observed in numerous carcinogenicity studies. The
      authors have evaluated pheochromocytoma concurrence with other effects and the
      possible mechanisms, in order to assess the relevance of such data for the
      classification of carcinogenic effects and their relevance to humans. The
      evaluation revealed that pheochromocytomas occur with relatively higher frequency
      in male rats, especially when the following conditions are involved: hypoxia,
      uncoupling of oxidative phosphorylation, disturbance in calcium homeostasis, and
      disturbance of the hypothalamic endocrine axis. The underlying biochemical
      mechanisms suggest that other substances that interfere with these biochemical
      endpoints also produce pheochromocytomas. Such endpoints include enzymes involved
      in catecholamine synthesis, receptor tyrosine kinase (RET), hypoxia-inducible
      factor (HIF), succinate dehydrogenase, fumarate hydratase, and pyruvate
      dehydrogenase. To date, there is no indication that the substances inducing
      pheochromocytomas in animal experiments also induce corresponding tumors in
      humans. Because the mechanisms of action identified in rats are to be expected in
      humans, pheochromocytomas may be induced after exposure conditions similar to
      those used in the animal studies. Whether hereditary mutations represent a risk
      factor in humans is not clear. Pheochromocytomas that occur in animal experiments
      currently appear to have little relevance for conditions at the work place. When
      sufficiently documented and evaluated, such secondary pheochromocytomas are not
      relevant for classification and human risk assessment.

PMID- 19743947
TI  - Antibacterial activities of amorphous cefuroxime axetil ultrafine particles
      prepared by high gravity antisolvent precipitation (HGAP).
AB  - In vitro and in vivo antibacterial activities on the Staphylococcus aureus and
      Escherichia coli of the amorphous cefuroxime axetil (CFA) ultrafine particles
      prepared by HGAP method were investigated in this paper. The conventional sprayed
      CFA particles were studied as the control group. XRD, SEM, BET tests were
      performed to investigate the morphology changes of the samples before and after
      sterile. The in vitro dissolution test, minimal inhibitory concentrations (MIC)
      and the in vivo experiment on mice were explored. The results demonstrated that:
      (i) The structure, morphology and amorphous form of the particles could be
      affected during steam sterile process; (ii) CFA particles with different
      morphologies showed varied antibacterial activities; and (iii) the in vitro and
      in vivo antibacterial activities of the ultrafine particles prepared by HGAP is
      markedly stronger than that of the conventional sprayed amorphous particles.

PMID- 19743948
TI  - Influence of sodium dodecyl sulfate on swelling, erosion and release behavior of
      HPMC matrix tablets containing a poorly water-soluble drug.
AB  - The effect of sodium dodecyl sulfate (SDS) on the swelling, erosion and release
      behavior of HPMC matrix tablets was examined. Swelling and erosion of HPMC matrix
      tablets were determined by measuring the wet and subsequent dry weights of
      matrices. The rate of uptake of the dissolution medium by the matrix was
      quantified using a square root relationship whilst the erosion of the polymer was
      described using the cube root law. The extent of swelling decreased with
      increasing SDS concentrations in the dissolution medium but the rate of erosion
      was found to follow a reverse trend. Such phenomena might have been caused by the
      attractive hydrophobic interaction between HPMC and SDS as demonstrated by the
      cloud points of the solutions containing both the surfactant and polymer. Release
      profiles of nimodipine from HPMC tablets in aqueous media containing different
      concentrations of SDS were finally studied. Increasing SDS concentrations in the
      medium was shown to accelerate the release of nimodipine from the tablets,
      possibly due to increasing nimodipine solubility and increasing rate of erosion
      by increasing SDS concentrations in the dissolution medium.

PMID- 19743949
TI  - Design and evaluation of San-huang dispersible tablet--an efficient delivery
      system for Traditional Chinese Medicine.
AB  - San-huang dispersible tablet (SHDT) was designed with a patented technology to
      enrich the active ingredients in rhubarb and with a wide selection of excipients
      in the new manufacturing procedure. The total rhubarb anthraquinones were first
      enriched in the extract by our patented technology. Eudragit L100, S100 and PEG
      6000 were used to release a part of the total rhubarb anthraquinones at the colon
      to induce the cathartic effect of the anthraquinones by another patented
      technology. Microcrystalline Cellulose (MCC), low-substituted hydroxypropyl
      cellulose (L-HPC), sodium carboxymethyl starch (CMS-Na), and hydroxypropyl
      methylcellulose (HPMC) were used to ensure quick release of baicalin and
      berberine hydrochloride in the stomach. The dissolution of SHDT was evaluated by
      a method in 2005 Chinese Pharmacopoeia along with San-huang tablet (SHT), and the
      results demonstrated that the dissolution of baicalin and berberine hydrochloride
      more than double that of SHT and release of half of the rhubarb anthraquinones in
      colon.

PMID- 19743950
TI  - Understanding drug-excipient compatibility: oxidation of compound A in a solid
      dosage form.
AB  - Drug-excipient compatibility studies lay the foundation for designing a
      chemically stable formulation for clinical and commercial development. This
      article describes the investigation of oxidative degradation encountered with
      compound A (a phenylalanine-drug complex) in a capsule dosage form. Two wet-
      granulation capsule formulations (2.5-mg and 25-mg strengths) were developed
      using excipients that showed satisfactory stability from initial drug-excipient
      compatibility studies. Both capsule strengths were chemically stable at 50
      degrees C (closed) for at least 18 weeks, but they showed discoloration. The 2.5
      mg capsule exhibited degradation after four weeks at 40 degrees C/75%RH (open)
      besides discoloration. LC/MS analysis indicated that the degradants were
      oxidation products of the parent compound. Oxidation of compound A was
      investigated by forced degradation with peroxide, use of isotopically labeled
      water (H2(18)O) to study the source of oxygen, and use of different antioxidants
      to mitigate oxidation. Excipient(s) responsible for oxidation and discoloration
      were identified through extended and modified excipient compatibility studies.
      The discoloration was indicative of Maillard reaction occurring between a
      reducing sugar impurity from microcrystalline cellulose and L-phenylalanine in
      the drug complex. Reactive oxidative species generated by this reaction is
      postulated to cause oxidation of compound A.

PMID- 19743952
TI  - Evaluation of a new method for the diagnosis of alterations of Lens culinaris
      agglutinin binding of thyroglobulin molecules in thyroid carcinoma.
AB  - BACKGROUND: The measurement of serum thyroglobulin (Tg) is widely used as a
      marker for recurrence of thyroid carcinoma following total thyroidectomy.
      However, this method cannot differentiate between benign and malignant disease.
      We focused on the sugar chain in the Tg molecule and investigated the usefulness
      of Lens culinaris agglutinin (LCA)-reactive Tg ratios in sera and wash fluids
      obtained during fine-needle aspiration (FNA) for the detection of thyroid
      carcinoma. METHODS: The study was performed using 203 serum samples (115 from
      patients with benign thyroid disease and 88 from patients with thyroid
      carcinomas) and 176 wash fluid samples (143 benign, 21 malignant, and 12
      inconclusive). LCA-reactive Tg ratios were determined using an enzyme-linked
      immunosorbent assay, and a comparison was made between malignant and benign
      lesions. RESULTS: In serum, the ratio in patients with malignancy was 79.5+/-6.0
      [mean+/-standard deviation (SD)], significantly lower than in patients with
      benign lesions (84.9+/-3.5). The ratios in wash fluid from malignant lesions
      (75.8+/-18.9) were also significantly lower than those from benign lesions
      (85.6+/-3.9). CONCLUSIONS: These results suggest that this method could
      distinguish between benign and malignant lesions and may be useful for screening
      serum and wash samples.

PMID- 19743953
TI  - Detection of Meningeosis neoplastica by real-time quantitation of telomerase
      activity.
AB  - BACKGROUND: Analysis of cerebrospinal fluid (CSF) to discriminate between benign
      and malignant conditions is of fundamental importance for the physician and the
      patient because of the differential therapeutic options and resulting morbidity
      and mortality. Most human tumours demonstrate increased telomerase activity (TA).
      Recent technical advances in the detection of TA allow for sensitive and specific
      detection within 4 h. Thus, the detection of TA is suitable for routine clinical
      testing. METHODS: This study examines TA in cellular proteins in CSF from 111
      patients compared to cytomorphological and laboratory examination. RESULTS: A
      positive result for TA in cellular proteins of CSF was correlated significantly
      with Meningeosis neoplastica, but not with non-malignant conditions. Telomerase
      was not detected in CSF supernatant, despite positive results in cellular
      proteins from identical patients. Furthermore, a 48-h time delay during the pre
      analytic processing is not critical for detection of TA detection in native CSF
      when stored at room temperature. CONCLUSIONS: We conclude that TA is a promising
      marker for the detection of Meningeosis neoplastica and warrants further study.

PMID- 19743954
TI  - The prognostic utility of haptoglobin genotypes in squamous cell carcinoma of the
      head and neck.
AB  - BACKGROUND: The aim of this study was to determine whether haptoglobin (Hp)
      genotypes are associated with prognosis in patients with squamous cell carcinoma
      of the head and neck (HNSCC). METHODS: We studied patients with HNSCC without
      distant metastasis at diagnosis. The Hp genotype of each patient was determined
      and the prognostic significance of the Hp genotype was further analyzed.
      Pearson's chi(2)-test or Fisher's exact test were used to analyze correlations
      between Hp genotype and clinical characteristics of HNSCC. Eighty patients with
      newly diagnosed HNSCC who were treated with curative modality were enrolled in
      this study. Kaplan-Meier plots and log-rank test were used to compare
      locoregional recurrence-free survival, distant-metastasis-free survival and
      overall survival of patients according to Hp genotype. Survival analysis was
      performed using Cox proportional hazard models. RESULTS: Eighty patients with
      newly diagnosed HNSCC were enrolled in this study. There was no significant
      difference in the distribution of Hp genotypes in HNSCC patients and healthy
      individuals (p=0.959). Matched-pair analysis showed that locoregional recurrence
      free survival was poor (p=0.02) for HNSCC patients with Hp 2-2 or 2-0. There was
      no significant difference in distant metastasis-free survival and overall
      survival (p=0.422 and 0.509, respectively). Multivariate analysis showed that Hp
      2-2 or 2-0 was associated with an increased risk of locoregional recurrence
      [Hazard ratio (HR) 5.9; 95% confidence interval (CI), 1.1-6.65; p=0.038]. The
      risk was still higher in patients with Hp 2-2 or 2-0 after further adjusting for
      age and treatment modality (HR 7.6; 95% CI, 1.2-46; p=0.028) in locoregional
      recurrence-free survival. CONCLUSIONS: The present data show that the Hp genotype
      is closely related to recurrence rate in patients with HNSCC. Patients with Hp 2
      2 or 2-0 have greater locoregional recurrence and significantly increased HRs in
      multivariate analysis. The Hp genotype may be a prognostic factor in patients
      with HNSCC.

PMID- 19743955
TI  - Polymorphisms of the beta1-adrenergic receptor gene are associated with essential
      hypertension in Chinese.
AB  - BACKGROUND: The beta1-adrenergic receptor (ADRB1) plays a pivotal role in
      mediating signal transduction of the sympathetic-adrenal system, which is
      involved in the regulation of cardiac output and peripheral resistance. Our goal
      was to determine whether the polymorphisms Arg389Gly (rs1801253) and Ser49Gly
      (rs1801252) of the ADRB1 gene were associated with essential hypertension in
      Chinese. METHODS: We tested our hypothesis in two independent case-control
      studies, one comprised 481 patients with hypertension and 529 control subjects,
      and the other study comprised 212 patients and 325 control subjects. All subjects
      were genotyped for Arg389Gly and Ser49Gly polymorphisms. RESULTS: The first study
      showed that the Arg389Arg genotype of the ADRB1 gene was associated with risk of
      hypertension [odds ratio (OR) 1.77, 95% confidence interval (CI) 1.09-2.98;
      p=0.008], and the association was replicated in the second independent population
      (OR 1.65, 95% CI 1.07-2.89, p=0.01). The patients with the Arg389Arg genotype had
      significantly higher diastolic blood pressure (DBP) than did those with Arg389Gly
      genotype as well as those with Gly389Gly genotype (100.29+/-11.01 mm Hg vs.
      95.33+/-13.10 mm Hg and vs. 96.17+/-12.18 mm Hg, respectively, p=0.01, p=0.02).
      The association was replicated in the second study (103.7+/-13.3 mm Hg vs.
      97.31+/-12.9 mm Hg and vs. 96.29+/-13.4 mm Hg, respectively, p=0.03, p=0.02).
      Heart rate also showed an association (in first study: 79.43+/-9.90 bpm vs.
      74.87+/-8.96 bpm, vs. 73.92+/-8.18 bpm, respectively, p=0.02, p=0.014; in the
      second study: 81.12+/-8.99 bpm vs. 74.85+/-7.97 bpm and vs. 73.89+/-9.12 bpm,
      p=0.007, p=0.006, respectively). No association was seen between systolic blood
      pressure (SBP) and any of the three genotypes at amino acid position 389 in
      hypertensive patients, neither between the Ser49Gly polymorphisms and
      hypertension, nor between the Ser49Gly genotypes and DBP and heart rate.
      CONCLUSIONS: The polymorphisms of the ADRB1 gene were associated with essential
      hypertension. The Arg389Gly polymorphism of the ADRB1 gene confers higher risk
      for hypertension.

PMID- 19743956
TI  - The soluble transferrin receptor (TfR)-F-Index is not applicable as a test for
      iron status in patients with chronic lymphocytic leukemia.
AB  - BACKGROUND: The soluble transferrin receptor (sTfR) is established as a test for
      iron deficiency (ID). In chronic lymphocytic leukemia (CLL), sTfR is not reliable
      for screening for ID as the latter is strongly dependent on tumor burden.
      METHODS: We investigated whether the influence of the tumor load can be excluded
      or minimized using the sTfR/log ferritin ratio (TfR-F-Index) and the C-reactive
      protein (CRP)-adjusted TfR-F-Index in 87 patients with CLL. sTfR was measured
      nephelometrically (normal: 0.81-1.75 mg/L). A cut-off value of 1.5 for the TfR-F
      Index and 0.8 for the CRP-adjusted TfR-F-Index, in patients with a CRP >5 mg/L,
      was used. RESULTS: All Binet A patients had normal sTfR values (1.34+/-0.2 mg/L),
      TfR-F-Index (0.67+/-0.2) and a CRP-adjusted TfR-F-Index. In Binet B and C, sTfR
      and the TfR-F-Index were significantly increased compared to Binet A patients
      (p<0.0001). The differences between Binet B and C were not significant. sTfR was
      increased in 85%, TfR-F-Index in 46% and the CRP-adjusted TfR-F-Index in 54% of
      the Binet B patients, in Binet C patients, 80%, 50% and 60% showed increases,
      respectively. sTfR and the TfR-F-Index decreased or even normalized following
      successful treatment. CONCLUSIONS: Similar to sTfR, the TfR-F-Index is strongly
      associated with tumor burden in patients with CLL. Thus, these parameters do not
      allow for a reliable diagnosis of ID in this patient group.

PMID- 19743957
TI  - Novel rare alleles of ABCA1 are exclusively associated with extreme high-density
      lipoprotein-cholesterol levels among the Han Chinese.
AB  - BACKGROUND: High-density lipoprotein (HDL) is a major plasma lipoprotein directly
      associated with cholesterol metabolism. The ATP binding cassette transporter 1
      gene (ABCA1) is one of the major genes modulating plasma levels of HDL
      cholesterol (HDL-C). Rare alleles of ABCA1 associated with extreme HDL-C
      concentrations have not been previously investigated in the Chinese. METHODS:
      Blood samples were collected from 470 subjects whose HDL-C concentrations were
      within the top 5% of the distribution, 335 subjects in the lowest 5%, and 220
      within the range 5%-95%. First, we sequenced all exons of the ABCA1 gene from 50
      subjects from the group with extremely high HDL-C, and 50 from the group with
      extremely low HDL-C concentrations. Next, in the remaining subjects, we genotyped
      the non-synonymous variants identified exclusively with either extreme group.
      RESULTS: Four novel non-synonymous alleles were identified; all were rare.
      Alleles c.3029C>T (p.Ala1010Val) and c.5399A>G (p.Asn1800Ser) were found
      exclusively in the low group, c.2031C>A (p.Asp677Glu) and c.2660G>T (p.Cys887Phe)
      exclusively in the high group. CONCLUSIONS: Our results show that some rare
      alleles of ABCA1 are associated with marked phenotypes, supporting the "rare
      variant common-disease" hypothesis. Certain alleles also provide tools for
      identifying individuals at high risk of dyslipidaemia, allowing for early
      therapeutic intervention.

PMID- 19743958
TI  - Evaluation of bone regeneration with an injectable, in situ polymerizable
      Pluronic F127 hydrogel derivative combined with autologous mesenchymal stem cells
      in a goat tibia defect model.
AB  - In situ forming bone substitute materials are attractive candidates for filling
      irregularly shaped defects. In this study, a chemically modified form of the
      Pluronic F127 hydrogel was used. Similar to the parent form, this derivative
      underwent a sol-gel transition in the body and additional radical curing resulted
      in a stable three-dimensional network gel with a controllable degradation rate.
      An extra cell source of autologous bone marrow-derived mesenchymal stem cells was
      mixed with the hydrogel to increase the ossification process, when implanted in
      noncritical size unicortical tibia defects. These cells were cultured and
      predifferentiated on two types of cell carrier systems, that is, gelatin
      CultiSpher-S microcarriers and hydroxyapatite tubular carriers. Radiographic and
      histological evaluation revealed that bone regeneration was comparable in the
      defects with the bone substitute compositions and the untreated control defects
      at 2 and 4 weeks postimplantation and that newly formed bone originated from the
      cells on the CultiSpher-S carriers. This resulted, 6 and 8 weeks
      postimplantation, in faster bone repair in the defects filled with the hydrogel
      plus CultiSpher-S carriers in comparison to the control defects. Surprisingly,
      there was no formation of new bone originating from the hydroxyapatite carriers.
      The hydrogel by itself seemed to stimulate the natural repair process.

PMID- 19743959
TI  - Comparison of incidences of cardiovascular events among new users of different
      statins: a retrospective observational cohort study.
AB  - OBJECTIVE: To compare incidences of cardiovascular disease (CVD) in general and
      myocardial infarction (MI) specifically between new users of different statins in
      daily practice. DESIGN AND METHODOLOGY: Retrospective observational cohort study.
      Data were obtained from the PHARMO Record Linkage System; the PHARMO database
      contains pharmacy dispensing records of 3 million patients in the Netherlands
      registered with community pharmacies, linked to hospitalisation records. The
      participants were new statin users in the period 2000-2005, excluding patients
      hospitalised for CVD events in the year prior to start of statin use. MAIN
      OUTCOME MEASURES: Adjusted hazard ratios of hospitalisations for CVD (including
      any type of ischemic heart disease, stroke, or revascularisation procedure) in
      general, or MI in particular, occurring during use of the initial statin within
      two years of start of therapy, comparing users of different statins. RESULTS: The
      mean follow-up duration of 76,147 new statin users (14,530 pravastatin, 27,752
      simvastatin, 25,777 atorvastatin, 8088 rosuvastatin) was 55 weeks. Incidence
      rates of CVD and MI per 100 person years ranged from 0.75 and 0.15 for
      rosuvastatin to 1.72 and 0.29 for pravastatin. Rosuvastatin users had a lower
      incidence rate of CVD compared to other statin users in general (28% lower), and
      simvastatin (29% lower) and pravastatin users (40% lower) in particular. The
      difference with atorvastatin was not statistically significant. Since this was
      not a prospective randomised study, there is the potential for unobserved risk
      factors to be responsible for some of the differences observed. CONCLUSION:
      Compared to other statin users without recent prior cardiovascular events, the
      incidence of fatal and non-fatal CVD in this retrospective observational cohort
      study was 28% lower among rosuvastatin users.

PMID- 19743961
TI  - In vivo comparison of simple and double-fractionated low-level laser irradiation
      schemes on the healing of rat skin lesions.
AB  - OBJECTIVE: To compare the efficacy of a simple irradiation scheme with that of a
      double-fractionated irradiation scheme on the healing of rat skin lesions using
      in vivo monitoring of tissue diffuse reflectance. BACKGROUND DATA: Low-level
      laser therapy (LLLT) is used in medicine for treating a wide range of
      pathological conditions. The practical benefits of laser treatment of acute and
      chronic conditions were obtained, using a single session of irradiation per day.
      MATERIALS AND METHODS: Thirty Wistar rats were divided into three experimental
      groups (controls, simple laser irradiation scheme, and double-fractionated laser
      irradiation scheme). A skin lesion was created on the calf of the right hind leg
      of all rats. The laser irradiation parameters were lambda = 635 nm and power = 15
      mW. The exposure time was 600 s for the simple laser irradiation scheme and 300 s
      x 2 for the double-fractionated laser irradiation scheme on 3 consecutive days.
      The optical properties of tissue were studied by processing and analyzing the
      diffuse reflectance spectra of injured skin, acquired before and after each laser
      irradiation. RESULTS: The results demonstrate that, using a simple laser
      irradiation scheme (single daily irradiation session: t exp 1 =600 s, power = 15
      mW, lambda = 635 nm), healing of the skin lesion began after 3 consecutive
      treatment days. The application of the double-fractionated laser irradiation
      scheme (2 daily irradiation sessions: t exp 2 = t exp 1/2 = 300 s, power = 15 mW
      and lambda = 635 nm) led to a reduction in treatment time to 2 days. CONCLUSION:
      In conclusion, a double-fractionated irradiation scheme is more efficient than
      simple irradiation scheme for LLLT in rat skin lesions.

PMID- 19743960
TI  - Mutational heterogeneity in human cancers: origin and consequences.
AB  - Cancer recapitulates Darwinian evolution. Mutations acquired during life that
      provide cells with a growth or survival advantage will preferentially multiply to
      form a tumor. As a result of The Cancer Genome Atlas Project, we have gathered
      detailed information on the nucleotide sequence changes in a number of human
      cancers. The sources of mutations in cancer are diverse, and the complexity of
      those found to be clonally present in tumors has increasingly made it difficult
      to identify key rate-limiting genes for tumor growth that could serve as
      potential targets for directed therapies. The impact of DNA sequencing on future
      cancer research and personalized therapy is likely to be profound and merits
      critical evaluation.

PMID- 19743962
TI  - The effect of equal daily dose achieved by different power densities of low-level
      laser therapy at 635 and 670 nm on wound tensile strength in rats: a short
      report.
AB  - OBJECTIVE: The aim of our study was to compare the effects of different power
      densities of LLLT at 635 and 670 nm achieving a daily dose of 5 J/cm(2) on wound
      tensile strength (TS) in rats. BACKGROUND DATA: Optimal parameters of low-level
      laser therapy (LLLT) are still unknown. MATERIALS AND METHODS: Under general
      anesthesia, one full-thickness skin incision was performed on the back of each
      rat (n = 40) and immediately closed using an intradermal running suture. Rats
      were separated into five groups depending on treatment parameters: (1) sham
      irradiated control group (SIC); (2) 635 nm laser-treated group at 4 mW/cm(2) (L
      635/4); (3) 635 nm laser-treated group at 15 mW/cm(2) (L-635/15); (4) 670 nm
      laser-treated group at 4 mW/cm(2) (L-670/4); and (5) 670 nm laser-treated group
      at 15 mW/cm(2) (L-670/15). The total daily dose was 5 J/cm(2). Seven days after
      surgery each wound was removed for wound TS measurement. RESULTS: The lowest
      wound TS results were measured in the SIC rats (10.5 +/- 2.8 g/mm(2)). Higher
      wound TS results were measured in group L-670/15 (11.5 +/- 2.5 g/mm(2)) and group
      L-635/4 (11.7 +/- 4.3 g/mm(2)) rats, while significantly higher results were
      found in group L-670/4 (15.8 +/- 4.4 g/mm(2)) and group L-635/15 (15.9 +/- 4.8
      g/mm(2)). The differences were significant between certain groups (p < 0.01: SIC
      vs. L-635/15, SIC vs. L-670/4; p < 0.05: L-635/4 vs. L-635/15, L-635/4 vs. L
      670/4, L-635/15 vs. L-670/15, L-670/4 vs. L-670/15). CONCLUSION: Both red lasers
      significantly increased wound TS at selected parameters. Whereas the 635 nm laser
      significantly improved wound healing by using the higher power density, the 670
      nm laser improved healing using a lower power density.

PMID- 19743963
TI  - Comparison of diode laser and Er:YAG lasers in the treatment of ankyloglossia.
AB  - OBJECTIVES: The purpose of this study was to compare the tolerance of lingual
      frenectomy with regard to a local anesthesia requirement and comparison of
      postsurgical discomfort experienced by patients operated on with both diode and
      erbium:yttrium-aluminium-garnet (Er:YAG) lasers. BACKGROUND: Ankyloglossia,
      commonly known as tongue-tie, is a congenital oral anomaly characterized by a
      short lingual frenulum. A short lingual frenulum may contribute to feeding,
      speech, and mechanical tongue problems. METHODS: Sixteen referred patients with
      tongue mobility complaints were included in this study. A GaAlAs laser device
      with a continuous wavelength of 808 nm was used in the diode group. Frenulums
      were incised by applying 2 W of laser power. The Er:YAG laser device with a
      continuous wavelength of 2940 nm was used in the Er:YAG group. Frenulums were
      incised by applying 1 W of laser power. The acceptability of the lingual
      frenectomy without local anesthesia and the degree of the postsurgical discomfort
      were evaluated. RESULTS: Although the majority of patients (six) could be
      operated on without local anesthesia in the Er:YAG group, all patients could not
      be operated on without local anesthetic agent in the diode group. There were no
      differences between the two groups with regard to pain, chewing, and speaking on
      the first or seventh day after surgery, whereas patients had more pain in the
      Er:YAG group than in the diode group the first 3 h after surgery. CONCLUSIONS:
      The results indicate that only the Er:YAG laser can be used for lingual
      frenectomy without local anesthesia, and there was no difference between the two
      groups regarding the degree of the postsurgical discomfort except in the first 3
      h. In conclusion, these results indicate that the Er:YAG laser is more
      advantageous than the diode laser in minor soft-tissue surgery because it can be
      performed without local anesthesia and with only topical anesthesia.

PMID- 19743965
TI  - Recent development of the mononuclear phagocyte system: in memory of Metchnikoff
      and Ehrlich on the 100th Anniversary of the 1908 Nobel Prize in Physiology or
      Medicine.
AB  - Monocytes/macrophages are critical for both immunity and homoeostasis. They are
      the outposts of the immune system in detecting invading pathogens or foreign
      antigens for homoeostatic clearance and antigen processing for the initiation and
      effector stages of both innate and adaptive immunity. In addition,
      monocytes/macrophages often function as control switches for immune system
      balance between pro- and anti-inflammatory reactions. In the beginning of this
      article, I would like to briefly introduce the achievements of Metchnikoff and
      Ehrlich in immunology, including Metchnikoff's cell theory, since they have both
      greatly influenced the advancement of modern immunology. Additionally, I will
      honour the 100th anniversary of the 1908 Nobel Prize in Physiology or Medicine.
      Next, I would like to emphasize the concept of the MPS (mononuclear phagocyte
      system) by examining recent developments regarding the MPS. Thus the article
      consists of three parts. The first part describes the regulation of growth and
      differentiation in the MPS. The second part addresses how the key macrophage
      transcription factor gene PU.1 and the csf1r (colony-stimulating factor-1
      receptor gene) play a critical role in haematopoietic myelopoiesis, or the
      generation of the cells of the MPS. The third part describes PMA-induced
      monocyte/macrophage differentiation and immune modulation of suppressor
      macrophages. Finally, this review discusses the latest findings and implications
      regarding the MPS and macrophages.

PMID- 19743964
TI  - The neurogenic basic helix-loop-helix transcription factor NeuroD6 concomitantly
      increases mitochondrial mass and regulates cytoskeletal organization in the early
      stages of neuronal differentiation.
AB  - Mitochondria play a central role during neurogenesis by providing energy in the
      form of ATP for cytoskeletal remodelling, outgrowth of neuronal processes, growth
      cone activity and synaptic activity. However, the fundamental question of how
      differentiating neurons control mitochondrial biogenesis remains vastly
      unexplored. Since our previous studies have shown that the neurogenic bHLH (basic
      helix-loop-helix) transcription factor NeuroD6 is sufficient to induce
      differentiation of the neuronal progenitor-like PC12 cells and that it triggers
      expression of mitochondrial-related genes, we investigated whether NeuroD6 could
      modulate the mitochondrial biomass using our PC12-ND6 cellular paradigm. Using a
      combination of flow cytometry, confocal microscopy and mitochondrial
      fractionation, we demonstrate that NeuroD6 stimulates maximal mitochondrial mass
      at the lamellipodia stage, thus preceding axonal growth. NeuroD6 triggers
      remodelling of the actin and microtubule networks in conjunction with increased
      expression of the motor protein KIF5B, thus promoting mitochondrial movement in
      developing neurites with accumulation in growth cones. Maintenance of the NeuroD6
      induced mitochondrial mass requires an intact cytoskeletal network, as its
      disruption severely reduces mitochondrial mass. The present study provides the
      first evidence that NeuroD6 plays an integrative role in co-ordinating increase
      in mitochondrial mass with cytoskeletal remodelling, suggestive of a role of this
      transcription factor as a co-regulator of neuronal differentiation and energy
      metabolism.

PMID- 19743966
TI  - Ten years of Nursing Philosophy.

PMID- 19743967
TI  - Three versions of an ethics of care.
AB  - The ethics of care still appeals to many in spite of penetrating criticisms of it
      which have been presented over the past 15 years or so. This paper tries to offer
      an explanation for this, and then to critically engage with three versions of an
      ethics of care. The explanation consists firstly in the close affinities between
      nursing and care. The three versions identified below are by Gilligan (1982), a
      second by Tronto (1993), and a third by Gastmans (2006), see also Little (1998).
      Each version is described and then subjected to criticism. It is concluded that
      where the ethics of care is presented in a distinctive way, it is at its least
      plausible; where it is stated in more plausible forms, it is not sufficiently
      distinct from nor superior to at least one other common approach to nursing
      ethics, namely the much-maligned 'four principles' approach. What is added by
      this paper to what is already known: as the article tries to explain, in spite of
      its being subjected to sustained criticism the ethics of care retains its appeal
      to many scholars. The paper tries to explain why, partly by distinguishing three
      different versions of an ethics of care. It is also shown that all three versions
      are beset with problems the least serious of which is distinctiveness from other
      approaches to moral problems in health care.

PMID- 19743968
TI  - Augmenting the Cartesian medical discourse with an understanding of the person's
      lifeworld, lived body, life story and social identity.
AB  - Using three paradigm cases of persons living with Parkinson's Disease (PD) the
      authors make a case for augmenting and enriching a Cartesian medical account of
      the pathophysiology of PD with an enriched understanding of the lived body
      experience of PD, the lived implications of PD for a particular person's concerns
      and coping with the illness. Linking and adding a thick description of the lived
      experience of PD can enrich caregiving imagination and attunement to the
      patient's possibilities, concerns and constraints. The work of Merleau-Ponty is
      used to articulate the middle terms of the lived experience of dwelling in a
      lifeworld. Examining lived experience of embodied intentionality, skilled bodily
      capacities as highlighted in Merleau-Ponty's non-mechanistic physiology opens new
      therapeutic, coping and caregiving possibilities. Matching temporal rhythms can
      decrease the stress of being assisted with activities of daily living. For
      example, caregivers and patients alike can be taught strategies for extending
      their lived bodily capacities by altering rhythms, by shifting hyperactivity to
      different parts of the body and other strategies that change the perceptual
      experience associated with walking in different environment. A medical account of
      the pathophysiology of PD is nessessary and useful, but not sufficient for
      designing caregiving in ways that enrich and extend the existential skills of
      dwelling of persons with PD. The dominance of mechanistic physiology makes
      caregivers assume that it is the 'real discourse' about the disease, causing
      researchers and caregivers alike to overlook the equally real lived experience of
      the patient which requires different descriptive discourses and different sources
      of understanding. Lack of dialogue between the two discourses is tragic for
      patients because caregivers need both in order to provide attuned, effective
      caregiving.

PMID- 19743969
TI  - Towards understanding the nature of conflict of interest and its application to
      the discipline of nursing.
AB  - Most incidences of dishonesty in research, financial investments that promote
      personal financial gain, and kickback scandals begin as conflicts of interest
      (COI). Research indicates that healthcare professionals who maintain COI
      relationships make less optimal and more expensive patient care choices. The
      discovery of COI relationships also negatively impact patient and public trust.
      Many disciplines are addressing this professional issue, but little work has been
      done towards understanding and applying this moral category within a nursing
      context. Do COIs occur in nursing and are they problematic? What are the morally
      appropriate responses to COI for our discipline and for individual practicing
      nurses? In this paper I examine the nature of 'conflict of interest' as a general
      ethical category, its characteristics and its application to our discipline.
      Conflict of interest is an odd moral category that may actually or potentially
      result in immoral decisions. The moral justification for COI is grounded prime
      facie by the moral value of respect for persons and principle of fidelity from
      which trust is developed and maintained. In review of the historical development,
      there appears to be consensus on some qualities of COI that are presented. I
      conclude that making judgements about COI are challenging and often difficult to
      determine from a nursing perspective. Improving nurses' and professional
      organizations' awareness of COI and sharpening our ability to respond
      appropriately when COI arise can reduce potential harm and promote trust in those
      whom we serve.

PMID- 19743970
TI  - A comprehensive theory of the human person from philosophy and nursing.
AB  - This article explores a problem of the articulation of an adequate account of the
      human person in both philosophical and nursing theory. It follows the lead of
      philosopher Norris Clarke in suggesting that there has been a significant
      division in the way philosophers have looked at the human person and goes on to
      suggest that this division is paralleled in prominent nursing theories. The paper
      reviews and argues for the synthesis of two contemporary philosophic theories of
      the person that arise from the traditional philosophical division, and uses
      Clarke's account to show the ontological need for such a synthesis if we are to
      have a more adequate account of the human person. Next, accounts of the person
      identified in a number of the prominent theories of nursing are briefly reviewed
      revealing the vast complexity of the person encountered in nursing practice. It
      is suggested that each new theory of nursing is founded, at least in part, on the
      need to account for attributes of the person missing from prior nursing theories.
      It will be seen that the synthesized account of the person argued for here more
      adequately accounts for the various attributes identified in these nursing
      accounts and it is hoped that this synthesized account will serve as a somewhat
      more complete basis for a continued exploration of the persons encountered in
      nursing practice in its many and varied manifestations.

PMID- 19743971
TI  - The issue of life: Aristotle in nursing perspective.
AB  - This paper explores the issue of life and its relevance to nursing, through
      Aristotle's philosophy and an Aristotelian interpretation of Nightingale's Notes
      on Nursing. Life as process and becoming has ontological status in Aristotle's
      philosophy and this dynamism is particularly relevant for nursing. The paper
      presents aspects of Aristotle's philosophy of life: his account of life as
      inherent powers of the individual, his analysis of change and time, and his
      understanding of sickness and health as qualitative states of living beings. It
      is shown how the Greek medical-philosophical tradition, continued by Galenic
      medicine and hygiene into modern time, influenced Nightingale's nursing.
      Individuals' life-maintaining metabolic relations to their surroundings are
      investigated through Aristotle and modern philosophy of biology and through
      Nightingale's nursing emphasis on the patient's relation to her or his immediate
      surroundings. It is argued that Nightingale's concern is really the processes of
      individual life, which in sickness necessitate temporally continuous nursing
      observation. Humans' radical dependency on their surroundings is actualized as
      interpersonal interdependency. The paper argues that the end of nursing care, the
      telos for which sake it is practised, is inherent in the individual course of the
      patients' life. When life processes are affected by sickness, infirmity, medical
      interventions or mental suffering, individuals need competent help to live - and
      to live as well as possible. It is suggested that the special responsibility of
      nursing is to facilitate, relieve and protect individual life continuously during
      such times.

PMID- 19743972
TI  - Why nursing has not embraced the clinician--scientist role.
AB  - Reasons for the limited uptake of the clinician-scientist role within nursing are
      examined, specifically: the lack of consensus about the nature of nursing
      science; the varying approaches to epistemology; and the influence of post-modern
      thought on knowledge development in nursing. It is suggested that under
      development of this role may be remedied by achieving agreement that science is a
      necessary, worthy pursuit for nursing, and that rigorous science conducted from a
      clinical perspective serves nursing well. Straddling practice and research is a
      powerful strategy for ensuring relevant research while forging strong links with
      practice. The clinician-scientist role, typically requiring a 75:25 ratio between
      research and clinical activities, is well established in medicine. Nursing,
      however, has been slow to institute the role; it is rare within North America,
      Australia, and western European countries, and almost non-existent outside those
      areas. Beyond structural obstacles, philosophical issues may explain nursing's
      reluctance to implement the role. Following a survey of clinician-scientist roles
      throughout the world, the nature of nursing science and epistemology, and the
      influence of post-modern thought on nursing attitudes to research are examined
      with respect to their influence on this role. The nurse clinician-scientist role
      holds promise for making strides in clinically relevant research, and for
      accelerating the knowledge cycle from clinical problem to research question to
      change in clinical practice.

PMID- 19743976
TI  - Collaborative working: piecing together the paediatric jigsaw.

PMID- 19743977
TI  - A review of nutrition in Duchenne muscular dystrophy.
AB  - Duchenne muscular dystrophy (DMD) is a recessive X linked genetic disorder
      characterised by progressive muscle weakness and reduced muscle tone. Affecting
      only boys, it limits life expectancy to approximately 20 years. A literature
      review was conducted using MEDLINE and the Cochrane Library, employing the term
      'Duchenne muscular dystrophy'. A total of 1491 articles in English were
      recovered. These papers were searched thematically under the headings: body
      composition (n = 10), energy expenditure (n = 10), nutrition (n = 6),
      corticosteroid therapy (n = 55) and gene therapy (n = 199). Key dietetic practice
      points were identified relevant to nutritional management. Papers supporting
      these key themes were assigned a level of evidence and grade of recommendation.
      There is limited high-quality evidence to guide the nutritional management of
      boys with DMD. Currently, the majority of evidence is based on expert opinion and
      clinical expertise. Delayed growth, short stature, muscle wasting and increased
      fat mass are characteristics of DMD and impact on nutritional status and energy
      requirements. The early introduction of steroids has altered the natural history
      of the disease, but can exacerbate weight gain in a population already
      susceptible to obesity. Prior to commencing steroids, anticipatory guidance for
      weight management should be provided. Malnutrition is a feature of end stage
      disease requiring a multidisciplinary approach, such as texture modification and
      supplemental feeding. Micronutrient requirements are yet to be determined but, as
      a result of corticosteroid treatment, vitamin D and calcium should be
      supplemented. Some evidence exists supporting supplementation with creatine
      monohydrate to improve muscle strength. More research is needed to provide a
      higher quality of evidence for dietitians working within this area.

PMID- 19743978
TI  - The nutritional intake supplied by enteral formulae used in older children (aged
      7-12 years) on home tube feeds.
AB  - BACKGROUND: In the UK, patients aged 6-12 years contribute more than one-third of
      children on home enteral tube feeds (HETF). Many enteral feeds are given to this
      age group. The present study aimed to investigate the formula with the best
      nutritional composition for children aged 7-12 years on HETF by comparing the
      nutrient intake of three feed types; a paediatric feed (PF) for 1-6 year olds, an
      adult feed (AF), and a feed for children (OCF) aged 7-12 years. METHODS: Twenty
      five HETF children aged 7-14 years (median 10 years) were given a 6.3 kJ mL(-1)
      enteral feed designed for 7-12 year olds (or weighing 21-45 kg) for 9 months.
      Nutrient intakes on the 7-12-year-old feed were compared with baseline feed
      (paediatric n = 10; or adult n = 15). RESULTS: At baseline, the PF failed to meet
      100% of the reference nutrient intake (RNI) for three of 19 (16%) of the
      nutrients studied, whereas AF provided in excess of 250% of the RNI for six of 19
      (32%) of the nutrients. During the trial, the nutrients on the OCF were two of 19
      (11%) <100% and four of 19 (21%) >250% of the RNI. Only seven of 10 (70%)
      children on a PF met at least 100% of the UK RNI for calcium, compared to 17 of
      19 (89%) on the OCF. CONCLUSIONS: It is important to offer older children an
      enteral feed that provides an optimal level of nutrients to meet their
      nutritional requirements. Feeds designed for 7-12-year-old children more closely
      meet nutrient requirements than paediatric or adult formulae, but require further
      modification to fully meet the nutritional needs of this group.

PMID- 19743979
TI  - Fibre content of enteral feeds for the older child.
AB  - BACKGROUND: There is currently a lack of clinical data on fibre requirements in
      UK children. Subsequently, the ideal fibre profile for enteral formulae designed
      to meet the requirements of older children is unknown. The present study aimed to
      investigate the effect of fibre supplementation on gastrointestinal function of
      children aged 7-12 years (or weight 21-45 kg) receiving an age-specific high
      energy enteral feed. METHODS: In this double-blind randomised crossover study, 25
      home enterally tube-fed children with a range of medical conditions (including
      cystic fibrosis, neurological conditions, liver transplant and bone marrow
      transplant) were given a 1.5 kcal mL(-1) formula with or without added dietary
      fibre (1.13 g per 100 mL). Each formula was taken for 6 weeks, followed by 6
      months on the second randomly assigned formula. Anthropometry, blood
      biochemistry, stool characteristics, tolerance and oral dietary intake were
      assessed. RESULTS: Despite a higher median fibre intake on the fibre-containing
      formula (84% versus 26% of recommended intake; P = 0.003), most children did not
      meet existing international recommendations for fibre as a result of small feed
      volumes (median 800 mL day(-1); 9 g fibre day(-1)). There was some evidence of
      reduced constipation, laxative reliance and abdominal pain on the fibre
      containing formula. CONCLUSIONS: Given the poor fibre intakes and absence of
      adverse effects, the use of fibre-containing formulae should become standard
      practice for the majority of children on enteral feeds. Larger trials in children
      are required to further evaluate the effect of amount and blend of fibre in
      enteral formulae for older children. However, it is likely that current formulae
      require higher levels of fibre.

PMID- 19743980
TI  - Long-term efficacy of 'ready-to-drink' protein substitute in phenylketonuria.
AB  - BACKGROUND: In phenylketonuria (PKU), protein substitute is an essential part of
      dietary treatment. Short-term studies have demonstrated that liquid protein
      substitutes (LPS) are efficacious, and improve compliance in teenagers and adults
      with PKU, although there are no data available to demonstrate that their
      effectiveness is sustained over time. The present retrospective study aimed to
      evaluate the long-term efficacy of ready-to-drink protein substitute in a group
      of people with PKU. METHODS: Thirty-four patients (17 females and 17 males,
      median age 14.9 years, range 7.2-53.8 years) with PKU on dietary management were
      recruited from Birmingham Children's Hospital. All patients who were taking a LPS
      for a median of 2.4 years (range 6 months to 4.1 years), had their plasma
      phenylalanine concentrations, anthropometric and nutritional biochemical markers
      reviewed, both before and when taking the LPS. RESULTS: There was a significant
      improvement in median plasma phenylalanine (P < 0.05), vitamin B(12) (P < 0.01),
      calcium (P < 0.05) and albumin (P < 0.05) concentrations in subjects (n = 13)
      aged >18 years when taking the LPS. In the children aged 7-18 years (n = 21),
      median plasma phenylalanine concentrations were maintained on LPS. Their plasma
      selenium concentrations (P < 0.05) deteriorated, but calcium (P < 0.05), albumin
      (P < 0.01), haemoglobin (P < 0.01) and haematocrit (P < 0.01) significantly
      improved. CONCLUSIONS: This retrospective review suggested that, in adult
      patients, the long-term use of LPS is associated with better compliance by
      lowering blood phenylalanine and improving nutritional biochemical markers.

PMID- 19743981
TI  - The impact of enteral feeding protocols on nutritional support in critically ill
      children.
AB  - BACKGROUND: Studies have shown that feeding protocols may assist in achieving
      optimal nutritional care in critically ill children. The present study aimed to
      assess the impact of enteral feeding protocols on nutritional support practices
      through a continuous auditing process over a defined period. MATERIALS AND
      METHODS: A prospective audit on nutritional practice was initiated in 1994-1995
      on all ventilated patients who were admitted for more than a complete 24-h period
      in the paediatric intensive care unit. The audit was repeated 1997-1998, 2001 and
      2005. The collection of data on outcomes included the time taken to initiate
      nutritional support, the proportion of patients fed via the enteral versus
      parenteral route, and the proportion of children reaching 50% and 70% of the
      estimated average requirement (EAR) by day 3. Feeding algorithms and protocols
      were introduced after each audit with a view to improving practices. RESULTS:
      Over the study period, time taken to initiate nutrition support was reduced from
      15 h (1994-1995), 8 h (1997-1998), 5.5 h (2001) to 4.5 h (2005). The proportion
      of patients on parenteral feeds was reduced from 11% (1994-1995) to 4% (2005). An
      increase was also documented in the percentage of patients receiving a daily
      energy provision of 50% and 70% of the EAR by day 3 after the initiation of
      nutritional support (6% in 1994-1995 to 21% in 2005 for 70% of EAR). CONCLUSION:
      The present study demonstrates that feeding protocols improve nutritional
      practices in a paediatric intensive care unit. However, protocol introduction
      needs to be monitored regularly through audit.

PMID- 19743982
TI  - Diet, physical activity, sedentary behaviour and perceptions of the environment
      in young adults.
AB  - BACKGROUND: Few studies have explored both food behaviour and physical activity
      in an environmental context. Most research in this area has focused on adults;
      the aim of the present study was to describe perceptions of the environment,
      diet, physical activity and sedentary behaviour patterns in 16-20 year olds in
      full-time education (Newcastle, UK). METHODS: Participants (n = 73) recruited
      from a college and sixth-form college completed a UK version of the Youth
      Neighbourhood Environment Walkability Survey, which included measures of
      sedentary behaviour. A validated food frequency questionnaire was completed and a
      factor applied to produce an estimated mean daily frequency of intake of each
      item, which was converted to nutrient intakes. A rank for Index of Multiple
      Deprivation (IMD) was assigned to their home postcode. Analysis explored
      associations between sedentary behaviours and nutrient intake. RESULTS: In this
      descriptive cross-sectional study, most participants reported being physically
      active for at least 1 h day(-1) on 3-4 (n = 28) or 5-7 days (n = 31). There were
      no significant differences in nutrient intake according to sample quartile IMD
      position. Sedentary behaviours were significantly associated with less healthy
      eating patterns. Higher total energy (P = 0.02), higher fat (P = 0.005),
      percentage energy from fat (P = 0.035) and lower carbohydrate intakes (P = 0.004)
      were significantly associated with more time spent watching DVDs at the weekend.
      CONCLUSIONS: This combination of sedentary behaviour and less healthy eating
      patterns has important implications for long-term health (e.g. the tracking of
      being overweight and obesity from adolescence into adulthood). Understanding
      behaviour relationships is an important step in developing interventions in this
      age group.

PMID- 19743983
TI  - The effect of including a conventional snack (cereal bar) and a nonconventional
      snack (almonds) on hunger, eating frequency, dietary intake and body weight.
AB  - BACKGROUND: With the increasing prevalence of being overweight and obesity,
      dietary strategies to curb hunger levels and increase satiety at lower energy
      intakes are sought. The frequency of eating and type of snack may influence total
      energy intake. The present study aimed to assess the impact of providing either a
      conventional snack (cereal bar) or a nonconventional snack (almonds) on eating
      frequency, hunger rating, dietary intake, body weight and blood lipids. METHODS:
      Forty-five healthy men (aged 25-50 years, body mass index = 25-35 kg m(-2)) were
      recruited and allocated to a control, cereal bar or almond snack group. Two
      packets of cereal bars and almonds were introduced for 12 weeks to the cereal bar
      group and the almond snack group, respectively. Dietary intakes and eating
      frequency were assessed by 4-day unweighed diet diaries; visual analogue scales
      were used to assess hunger ratings; and fasting blood parameters (i.e. glucose,
      insulin, total cholesterol, triglycerides, low-density lipoprotein cholesterol
      and high-density lipoprotein cholesterol) were measured at baseline, 6 and 12
      weeks. In addition, anthropometric measures (height, weight, skinfold thickness,
      waist and hip circumference) were measured at baseline, 6 and 12 weeks. RESULTS:
      The present study found no significant change in the eating frequency within
      groups at 12 weeks. However, the almond snack group had a significantly higher
      eating frequency than the control group (P < or = 0.05) and cereal bar group (P <
      or = 0.01). This did not result in higher energy intake, body weight or
      percentage body fat in the almond snack group. CONCLUSION: The present study
      demonstrated that snacking on almonds, in comparison to cereal bars, promoted a
      higher eating frequency, but not a higher energy intake. Advice to snack on
      either almonds or cereal bars did not result in weight gain, suggesting that
      energy compensation took place.

PMID- 19743984
TI  - Impact of some isoenergetic snacks on satiety and next meal intake in healthy
      adults.
AB  - BACKGROUND: Choosing small portions especially of low energy foods is a standard
      recommendation for weight management. However, this can result in rapid return of
      hunger or an increase in the next meal size. Enhancing the satiating capacities
      of low energy foods may help to overcome these effects. The present study
      compared the satiating properties of small servings of four low energy foods [465
      kJ (111 kcal)] including a drinking yogurt enhanced for satiety. METHODS: Thirty
      volunteers attended the laboratory to consume isoenergetic preloads of: a fibre
      enriched drinking yogurt, a regular drinking yogurt, plain crackers, fresh
      banana; or an isovolumetric serving of water. Satiety was analysed using visual
      analogue scales, before and every 15 min after consumption for 60 min, when ad
      libitum food intake was measured. RESULTS: The yogurts and the banana were more
      satiating than water and crackers (P < 0.001 for yogurts and banana versus
      crackers and water). Only the fibre-enriched yogurt produced higher satiety
      scores than crackers at 60 min (P < 0.05). Mean + or - SD consumption at next
      meal was: fibre-enriched yogurt 2050 + or - 787 kJ (490 + or - 188 kcal); regular
      yogurt 2071 + or - 575 kJ (495 + or - 137 kcal); bananas 2178 + or - 603 kJ (520
      + or - 144 kcal); crackers 2232 + or - 590 kJ (533 + or - 141 kcal); water 2519 +
      or - 741 kJ (602 + or - 177 kcal); (yogurts versus water: P = 0.001; bananas
      versus water: P = 0.013; crackers versus water: P = 0.064), demonstrating
      accurate energy compensation for the yogurts only. CONCLUSIONS: Although there
      were no significant differences between the different foods' satiating capacity,
      a trend for the following ranking was found: fibre-enriched yogurt > regular
      yogurt > banana > crackers > water. Overall, the fibre-enriched drinking yogurt
      tended to be more satiating than the other foods.

PMID- 19743985
TI  - Frequent consumption of certain fast foods may be associated with an enhanced
      preference for salt taste.
AB  - BACKGROUND: Excessive exposure to high-salt foods may change the taste
      perception, which results in the overconsumption of sodium. The present study
      aimed to investigate the effects of liking or frequent eating of high-salt food
      on salt taste perception among schoolchildren. METHODS: The detection threshold
      of sodium chloride (NaCl) and the preferred salinity of beansprout soup were
      determined and were used to represent the salt taste acuity and preference,
      respectively, of 70 Koreans aged 12-13 years. A self-administered questionnaire
      was used to obtain information regarding food preferences or frequency of eating
      certain high-salt Korean dishes, Westernised fast foods and commercially-prepared
      foods, as well as various food groups. The significance of differences in taste
      perceptions was assessed in relation to the reported liking, and frequency of
      eating, high-salt foods. In addition, the correlation between taste perception
      and the liking or frequency of eating fast foods was also assessed. RESULTS: The
      participants who reported a liking for soup/stew had significantly higher
      thresholds for NaCl (P = 0.029), and frequent users of fast-food restaurants
      showed a preference for significantly saltier soup (P = 0.010). The preferred
      salinity was associated significantly with a high preference for pizza (r =
      0.282, P = 0.018) or hamburgers (r = 0.305, P = 0.010) and the frequent
      consumption of pork cutlets (r = 0.239, P = 0.046) or hamburgers (r = 0.461, P =
      0.010). CONCLUSIONS: The results obtained in the present study suggest that the
      frequent consumption of certain fast foods by young teenagers may be associated
      with an increased preference for salt taste. This study provides basic
      information for use in devising education programmes in evidence-based nutrition
      to reduce salt intake.

PMID- 19743991
TI  - Is longer duration of proton pump inhibitor trial better for gastroesophageal
      reflux disease-related non-cardiac chest pain?

PMID- 19743992
TI  - Prognosticating gastric cancer.

PMID- 19743993
TI  - Minimally invasive prediction of esophageal varices and portal hypertension.

PMID- 19743994
TI  - Mechanism of portal hypertensive gastropathy: an unresolved issue.

PMID- 19743995
TI  - Ascites and spontaneous bacterial peritonitis: an Asian perspective.
AB  - Ascites is the most common complication of liver cirrhosis, and it develops as a
      consequence of portal hypertension and splanchnic vasodilatation. Depending on
      severity, management of ascites consists of diverse strategy, including dietary
      sodium restriction, diuretic therapy, repeated large-volume paracentesis with
      albumin infusion, transjugular intrahepatic portosystemic shunt, and liver
      transplantation. Recently, advances in medical therapy have been made with
      satavaptan, a V2 receptor antagonist, vasoconstrictors, such as clonidine,
      midodrine, or terlipressin, and other categories of drugs, including docarpamine
      and Chinese herbs. These drugs may serve as useful adjuncts to conventional
      diuretics in the management of ascites. Besides ascites itself, serious
      complications, such as spontaneous bacterial peritonitis (SBP) and hepatorenal
      syndrome, frequently ensue in decompensated cirrhosis. SBP develops from the
      translocation of bacteria from the intestine, and successful management with
      early diagnosis and treatment with proper prevention in patients of high risk is
      necessary. In summary, ascites is a starting point for more serious complications
      in liver cirrhosis. Although liver transplantation is the fundamental treatment,
      it is not always feasible, and consequently various means of treatment should be
      used. Further study, particularly in Asia where hepatitis B virus-related
      cirrhosis is predominant, is warranted to improve the clinical outcome.

PMID- 19743996
TI  - Patient satisfaction after endoscopic retrograde cholangiopancreatography for
      biliary stones: a prospective multicenter study in Lombardy.
AB  - AIMS: To measure patients' satisfaction after endoscopic retrograde
      cholangiopancreatography (ERCP) for biliary stones in a large number of
      unselected endoscopy units. METHODS: A prospective study using a questionnaire
      (Group Health Association of America-9 [GHAA-9], modified) was administered 24 h
      and 30 days after the procedure. Patients undergoing endoscopy for biliary stones
      for the first time were enrolled in a large number of endoscopy units, regardless
      of their size and workload. RESULTS: In all, 700 patients were enrolled in 15
      units. A high proportion of patients expressed satisfaction (80%). Satisfaction
      was less extensive for pain control and the quality of information provided
      before the procedure. There were no differences in the replies to questionnaires
      at 24 h and 30 days. CONCLUSION: It is feasible to record patients' satisfaction
      and in this series most patients were very satisfied. Criticisms concerned pain
      control and explanations provided before the procedure.

PMID- 19743997
TI  - En-bloc resection of multiple type 1 gastric carcinoid tumors by endoscopic multi
      band mucosectomy.
AB  - BACKGROUND AND AIM: Gastric carcinoid tumors are rare but increasing in
      incidence. Current recommendations suggest endoscopic resection for type I
      carcinoids found in the stomach, however reports of incomplete resection have led
      to difficulty planning future management. Our purpose was to describe the
      application of the endoscopic multi-band mucosectomy (MBM) device to achieve en
      bloc resection of multiple gastric carcinoid tumors. METHODS: Over a 30-month
      period (June 2006-January 2009) eight patients attending for endoscopic
      assessment of gastric carcinoid tumors were identified at two tertiary referral
      centers. Patients underwent endoscopic resection of the carcinoids with an MBM
      device. En-bloc specimens underwent histological evaluation for identification
      and tumor resection margins. Patients with type I carcinoids were subsequently
      enrolled in an endoscopic follow-up program. RESULTS: A total of 34 gastric
      carcinoid tumors were removed from eight patients. On histological analyses seven
      out of eight patients were diagnosed with type I tumors. In the remaining patient
      a single, sporadic (type III) gastric carcinoid was diagnosed. No complications
      of severe bleeding or perforation occurred. All specimens were shown to have
      clear deep and peripheral histological resection margins. CONCLUSION: Complete
      'en-bloc' endoscopic resection of multiple 'type I' gastric carcinoid tumors can
      be safely and easily performed with an MBM technique.

PMID- 19743998
TI  - Underlying mechanism of portal hypertensive gastropathy in cirrhosis: a
      hemodynamic and morphological approach.
AB  - BACKGROUND AND AIM: Portal hypertensive gastropathy (PHG) is an important cause
      of bleeding in patients with cirrhosis associated with portal hypertension.
      Histologically, the condition is characterized by dilation of the mucosal and
      submucosal vessels of the stomach; however, its mechanisms remain unclear. The
      aim of the present cross-sectional study was to evaluate the role of portal and
      systemic hemodynamic features, humoral factors and hepatocellular function in the
      development and severity of PHG in patients with cirrhosis. METHODS: Forty-six
      patients with cirrhosis of different etiologies underwent endoscopy. Portal
      hypertension was evaluated by hepatic venous pressure gradient (HVPG). The
      gastric mucosa was analyzed using two diagnostic methods: endoscopy according to
      the McCormack criteria and histological by histomorphometric analysis. RESULTS:
      The prevalence of PHG according to the endoscopic and histomorphometric methods
      was 93.4% and 76.1%, respectively. There were no statistically significant
      differences in HVPG measurements between the patients with mild (16.0 +/- 5.9
      mmHg) and severe PHG (16.9 +/- 6.5 mmHg; P = 0.80) or between patients who did
      not have (15.2 +/- 8.0 mmHg) and those who had PHG (16.3 +/- 5.7 mmHg). No
      correlation was found between the presence or severity of PHG and systemic
      vascular resistance index (P = 0.53 and 0.34, respectively), Child-Pugh
      classification (P = 0.73 and 0.78, respectively) or glucagon levels (P = 0.59 and
      0.62, respectively). CONCLUSIONS: The present data show no correlation between
      the presence or the severity of PHG and portal pressure, Child-Pugh
      classification or systemic hemodynamics, suggesting that other factors may be
      involved in the physiopathology of PHG, such as local gastric mucosal factors or
      other underlying factors.

PMID- 19743999
TI  - Effect of laparoscopic splenectomy on portal hypertensive gastropathy in
      cirrhotic patients with portal hypertension.
AB  - AIM: This study investigated the relationship between portal hypertensive
      gastropathy (PHG) and splenomegaly, and the effect of laparoscopic splenectomy on
      PHG in cirrhotic patients with portal hypertension. METHODS: Seventy patients
      with liver cirrhosis and portal hypertension were prospectively studied.
      Indication for laparoscopic splenectomy was bleeding tendency in 10 patients,
      induction of interferon in 45, treatment of hepatocellular carcinoma in seven,
      and treatment for endoscopic injection sclerotherapy-resistant esophagogastric
      varices in eight. The severity of PHG was classified into none, mild, or severe
      according to the classification by McCormack et al. The severity of liver disease
      was classified using the Child-Pugh score. All patients underwent upper
      gastrointestinal endoscopy before and 1 month after the operation. RESULTS: The
      prevalence of PHG was significantly correlated with the severity of liver disease
      using the Child-Pugh score. The severity of PHG was significantly correlated with
      the resected spleen volume. One month after the operation, PHG was improved in 16
      of 17 patients with severe PHG and in 12 of 32 with mild PHG. The Child-Pugh
      score showed a significant improvement (6.8 +/- 1.4 to 6.2 +/- 1.2) at 3 months
      after laparoscopic splenectomy (P < 0.0001). CONCLUSIONS: PHG may be associated
      with splenomegaly, and laparoscopic splenectomy may have a beneficial effect on
      PHG, at least for a short time.

PMID- 19744000
TI  - Inflammatory pseudotumors of the liver: experience of a specialist surgical unit.
AB  - BACKGROUND AND AIM: To present the experience in management of inflammatory liver
      pseudotumors from a specialist surgical unit and to review the medical literature
      on this rare manifestation. METHODS: Between 1995 and 2008, four patients were
      identified with this type of tumor from a total of 108 resected benign liver
      lesions at the Royal Infirmary of Edinburgh, Scotland UK. Two patients presented
      with liver abscesses, one with liver cystadenoma, and one with hilar
      cholangiocarcinoma. All four underwent some type of hepatectomy. We report these
      cases and review the literature. RESULTS: All four patients survived the
      operation with some morbidity. CONCLUSIONS: Inflammatory liver pseudotumors are a
      difficult entity to identify. Resection should be considered because it may be
      impossible to rule out malignancy by other means.

PMID- 19744001
TI  - Plasma concentrations of growth arrest-specific protein 6 and protein S in
      patients with acute pancreatitis.
AB  - BACKGROUND: The aim of the present study was to clarify the changes in plasma
      concentrations of growth arrest-specific protein 6 (Gas6) and protein S (PS) in
      patients with mild or severe acute pancreatitis (AP). METHODS: The study group
      comprised 29 consecutive patients with AP (24 males, five females; mean age, 54.8
      +/- 15.0 years) and 20 healthy controls (10 males, 10 females; mean age, 53.0 +/-
      15.3 years). Plasma concentrations of Gas6 and PS were measured by enzyme-linked
      immunosorbent assay. RESULTS: The concentration of Gas6 was significantly higher
      in both severe and mild AP than in healthy controls, and was significantly
      correlated with two of the multiple organ failure assessment scores. Furthermore,
      when compared with survivors, the concentrations of Gas6 in non-survivors of
      severe AP were significantly increased. The concentrations of free PS and total
      PS were significantly decreased compared with normal controls, but there was no
      difference between cases and controls in the concentrations of C4 binding protein
      PS. CONCLUSION: Plasma concentrations of Gas6 and PS correlate with disease
      severity. High concentrations of Gas6 reflect microcirculatory abnormalities, and
      phagocytosis of dying cells in sepsis associated with severe AP.

PMID- 19744002
TI  - Education and imaging: Hepatobiliary and pancreatic: autoimmune pancreatitis.

PMID- 19744003
TI  - Education and imaging: Hepatobiliary and pancreatic: liver abscess caused by an
      ingested foreign body.

PMID- 19744004
TI  - Education and imaging: Gastrointestinal: pachydermoperiostosis associated with
      Crohn's disease.

PMID- 19744006
TI  - Critical review of ropinirole and pramipexole - putative dopamine D(3)-receptor
      selective agonists - for the treatment of RLS.
AB  - Ropinirole hydrochloride (REQUIP, ADARTREL) and pramipexole dihydrochloride
      (MIRAPEX, SIFROL) are two putative dopamine D(3) receptor subtype-selective
      agonists recently approved by the FDA for the treatment of 'restless legs
      syndrome' (RLS). RLS is a difficult to define condition that is possibly more
      prevalent than previously thought. Direct-to-consumer advertising has raised
      public and professional awareness of RLS, but questions, even skepticism about
      the very existence of the condition, persist. The drugs have adverse effects that
      can negatively impact on quality of life and thus, as true for all drugs, require
      consideration of the benefit : risk ratio. We review the definition, diagnostic
      criteria, pathophysiology, and treatment of RLS, and assess the clinical and
      preclinical evidence for a pharmacologic rationale for D(3) agonism in general
      and of the claimed D(3) selectivity of ropinirole and pramipexole in particular.

PMID- 19744007
TI  - Bioavailability of oral vitamin E formulations in adult volunteers and children
      with chronic cholestasis or cystic fibrosis.
AB  - PURPOSE: To test bioequivalence of oral vitamin E formulations, water-soluble
      tocofersolan (test) and water-miscible (reference), in healthy adult volunteers,
      and their bioavailability in children with chronic cholestasis or cystic
      fibrosis. METHODS: In a two-way open randomized single dose cross-over design,
      1200 IU were administered in 12 healthy volunteers and 100 IU/kg in 12 children
      with chronic cholestasis or cystic fibrosis. RESULTS: In healthy volunteers,
      formulations were not bioequivalent with a higher exposure to tocofersolan. In
      cholestatic children tocofersolan bioavailability was significantly higher than
      reference formulation (maximum plasma concentration: P = 0.008 and AUC: P =
      0.0026). Bioavailability was not statistically different in cystic fibrosis.
      CONCLUSIONS: Oral tocofersolan was more bioavailable than the reference
      formulation in children with chronic cholestasis and similarly bioavailable in
      cystic fibrosis. Tocofersolan may represent an alternative to painful
      intramuscular vitamin E injections in chronic cholestasis, or to other oral
      formulations in cystic fibrosis.

PMID- 19744008
TI  - Validated LC coupled to ESI-MS/MS analysis for fentanyl in human plasma and UV
      analysis in applied reservoir transdermal patches using a simple and rapid
      procedure.
AB  - BACKGROUND AND OBJECTIVES: Fentanyl has been used for cancer pain in transdermal
      formulation. The aim of the present study was to establish an analytical method
      for fentanyl in human plasma and in an applied transdermal reservoir patch
      (Reservoir-TTS), as well as for therapeutic monitoring of fentanyl in cancer
      patients. METHOD: Electro-spray ionization mass spectrometric (ESI-MS/MS)
      analysis followed solid phase extraction (SPE) from human plasma and drug
      reservoir extraction from an applied Reservoir-TTS. Each separation was completed
      within 9 min using an ODS column (particle size, 3 microm, 2.0 mm i.d. x 75 mm)
      with 25% acetonitrile containing 5 mm ammonium acetate at pH 3.5. In the ESI
      MS/MS analysis, the calibration curve for fentanyl was linear over a
      concentration range of 0.05-7.2 ng/mL in human plasma. The extraction efficiency
      of fentanyl in the human plasma was more than 95%. The intra- and interassay
      precision and accuracy were within 7% and 97.3-101.2%, respectively. The lower
      LOQ for fentanyl was 0.05 ng/mL in the human plasma. The extraction of the 25
      microg/h and 50 microg/h Reservoir-TTS gave reproducible recoveries of 88.3% and
      90.9%, respectively. The plasma concentration of fentanyl showed large
      interindividual variation in 31 patients with cancer pain. CONCLUSION: The method
      described is simple, accurate, and reproducible, and should be helpful for the
      therapeutic monitoring of fentanyl in cancer patients.

PMID- 19744009
TI  - Cyclosporine pharmacological efficacy estimated by lymphocyte immunosuppressant
      sensitivity test before and after renal transplantation.
AB  - OBJECTIVE: Lymphocyte immunosuppressant sensitivity test (LIST) is useful for
      predicting the pharmacological efficacy of immunosuppressive agents. In this
      study, the pharmacological efficacy of cyclosporine was estimated by LIST before
      and after renal transplantation. METHODS: Lymphocyte immunosuppressant
      sensitivity test was performed by the 3-(4,5-dimethylthiazol-2-yl)
      2,5diphenyltetrazolium bromide (MTT) assay before and at 1, 3, and 12 months
      after transplantation in 19 consecutive renal transplant recipients. RESULTS:
      There was wide intersubject variability in cyclosporine IC50 before
      transplantation [Mean (SD) of 593.9 (1067.6) ng/mL]. This variability worsened 1
      month after transplantation [525.7 (1532.7) ng/mL] but decreased at 3 months
      (193.5 (347.9) ng/mL) and 12 months (75.4 (95.4) ng/mL). In this small study,
      observed differences in IC50 values for the individual subjects at various time
      intervals was not associated with the occurrence of rejection, graft loss, and
      infection episodes. CONCLUSION: Lymphocyte sensitivity to cyclosporine assessed
      by the LIST assay showed a high level of inter-subject variability particularly
      before and 1 month after transplantation. The observed difference in IC50 values
      was not associated with clinical outcome in this small study.

PMID- 19744010
TI  - Generic medicines: Greek physicians' perceptions and prescribing practices.
AB  - BACKGROUND AND OBJECTIVE: The penetration of generic drugs in the Greek
      pharmaceutical market is placed among the weakest in the EU. The Greek regulatory
      framework does not systematically support the development of this subsector and
      physicians are not provided with incentives for prescribing generics. The aim of
      this study was to investigate the prescribing profile of physicians in Greece
      with a focus on the factors that influence their decision on generics
      prescribing. METHODS: A structured questionnaire was sent by mail to a random
      national sample of 1463 physicians, stratified by sex, specialty and geographical
      region. RESULTS AND DISCUSSION: The response rate was 82.3%. Greek physicians
      have a positive view on generics but they prefer to prescribe the original
      products. According to our analysis, physician's age and their opinion on
      generics' efficacy and effectiveness are identified as important determinants of
      their prescribing decision. The primary reason that could make them change their
      prescribing habits is the appearance of side-effects. Patients' insurance
      coverage and income, as well as the drug cost are also referred as factors that
      influence their prescribing decision. Despite the fact that they do not usually
      prescribe generics in their clinical practice, they are willing to substitute an
      original drug by a generic product. CONCLUSIONS: Our findings suggest that Greek
      physicians could be persuaded to prescribe generic medicines, if a generic
      promotion policy was introduced in the country. To develop such a policy, a set
      of supply side and demand-side measures should be implemented along with
      provision of information on generics to physicians during their education and
      clinical practice.

PMID- 19744011
TI  - Lack of association between ACE and bradykinin B2 receptor gene polymorphisms and
      ACE inhibitor-induced coughing in hypertensive Koreans.
AB  - BACKGROUND & OBJECTIVE: Angiotensin converting enzyme (ACE) inhibitors are used
      widely in therapy for hypertension, congestive heart failure and myocardial
      infarction. However, coughing, one of their major adverse effects limits their
      use. It is documented that Asians are more liable to coughing than Europeans. The
      aim of this study was to investigate genetic polymorphism involved in ACE
      inhibitor-induced coughing. METHODS: We monitored hypertensive subjects (n = 110)
      treated with ACE inhibitors, and tested for any associations between ACE
      inhibitor-induced coughing and polymorphisms in the genes for ACE and the
      bradykinin B2 receptor, which are suspected to be related to coughing. RESULTS &
      DISCUSSION: We found no significant differences between the groups with coughing
      and without coughing in the frequency of ACE I/D (Insertion/Deletion)
      polymorphisms. One single nucleotide polymorphism was discovered in the promoter
      (-58T/C) and, one in intron-exon junction upsteam of exon 2 (-59C/A), of the
      bradykinin B2 receptor gene. However, no significant correlation was found
      between those genotypes or allele distributions and ACE inhibitor-induced
      coughing. CONCLUSION: We found no significant links between polymorphisms of the
      ACE gene or bradykinin B2 receptor gene with ACE inhibitor-induced coughing in
      hypertensive Koreans. But, the topic remains controversial and requires more
      study.

PMID- 19744012
TI  - Effect of CYP3A5*3 genotype on serum carbamazepine concentrations at steady-state
      in Korean epileptic patients.
AB  - BACKGROUND AND OBJECTIVE: Carbamazepine (CBZ) is metabolized mainly by the CYP3A
      family of enzymes, which includes CYP3A4 and CYP3A5. Several studies have
      suggested that the CYP3A5*3 genotype influences the pharmacokinetics of CYP3A
      substrates. The present study aimed to assess the effect of the CYP3A5*3 genotype
      on serum concentration of CBZ at the steady-state in Korean epileptic patients.
      METHOD: The serum concentrations of CBZ in 35 Korean epileptic patients were
      measured and their CYP3A5 genotype was determined. Fourteen patients were CYP3A5
      expressors (two for CYP3A5*1/*1 and 12 for CYP3A5*1/*3) and 21 patients were
      CYP3A5 non-expressors (CYP3A5*3/*3). Dose-normalized concentrations (mean +/- SD)
      of CBZ were 9.9 +/- 3.4 ng/mL/mg for CYP3A5 expressors and 13.1 +/- 4.5 ng/mL/mg
      for CYP3A5 non-expressors (P = 0.032). The oral clearance of CBZ was
      significantly higher in CYP3A5 non-expressors than that of CYP3A5 expressors
      (0.056 +/-0.017 L/h/kg vs. 0.040 +/- 0.014 L/h/kg, P = 0.004). The CYP3A5
      genotype affected the CBZ concentrations in Korean epileptic patients and is a
      factor that may contribute to inter-individual variability in CBZ disposition in
      epileptic patients.

PMID- 19744013
TI  - Pharmacokinetics and pharmacodynamics of prasugrel in subjects with moderate
      liver disease.
AB  - BACKGROUND AND OBJECTIVE: Prasugrel is a thienopyridine antiplatelet agent under
      investigation for the prevention of atherothrombotic events in patients with
      acute coronary syndrome who undergo percutaneous coronary intervention. Patients
      with chronic liver disease are among those in the target population for
      prasugrel. As hepatic enzymes play a key role in formation of prasugrel's active
      metabolite, hepatic impairment could affect the safety and/or efficacy of
      prasugrel in such patients. METHODS: This was a parallel-design, open-label,
      multiple dose study of 30 subjects, 10 with moderate hepatic impairment (Child
      Pugh Class B) and 20 with normal hepatic function. Prasugrel was administered
      orally as a 60-mg loading dose (LD) and daily 10-mg maintenance doses (MDs) for 5
      days. Pharmacokinetic parameters (AUC(0-t), C(max) and t(max)) and maximal
      platelet aggregation (MPA) by light transmission aggregometry were assessed after
      the LD and final MD. RESULTS AND DISCUSSION: Exposure to prasugrel's active
      metabolite was comparable between healthy subjects and those with moderate
      hepatic impairment. Point estimates for the ratios of geometric least square
      means for AUC(0-t) and C(max) after the LD and last MD ranged from 0.91 to 1.14.
      MPA to 20 microm ADP was similar between subjects with moderate hepatic
      impairment and healthy subjects for both the LD and MD. Prasugrel was well
      tolerated by all subjects, and adverse events were mild in severity. CONCLUSION:
      Moderate hepatic impairment appears to have no effect on exposure to prasugrel's
      active metabolite. Furthermore, MPA results suggest that moderate hepatic
      impairment has little or no effect on platelet aggregation relative to healthy
      controls. Overall, these results suggest that a dose adjustment would not be
      required in moderately hepatically impaired patients taking prasugrel.

PMID- 19744014
TI  - Prasugrel pharmacokinetics and pharmacodynamics in subjects with moderate renal
      impairment and end-stage renal disease.
AB  - OBJECTIVE: The pharmacokinetic (PK) and pharmacodynamic (PD) responses to
      prasugrel were compared in three studies of healthy subjects vs. those with
      moderate or end-stage renal impairment. METHODS: Two of the three protocols were
      parallel-design, open-label, single dose (60-mg prasugrel) studies in subjects
      with end-stage renal disease (ESRD; n = 12) or moderate renal impairment (n = 10)
      and matched healthy subjects with normal renal function (n = 10). The third
      protocol was an open-label, single-dose escalation (5, 10, 30 and 60 mg
      prasugrel) study in subjects with ESRD (n = 16) and matched healthy subjects with
      normal renal function (n = 16). Plasma concentrations of prasugrel's active
      metabolite were determined and pharmacokinetic parameter estimates were derived.
      Maximum platelet aggregation (MPA) was measured by light transmission
      aggregometry using 20 mum adenosine diphosphate as agonist. RESULTS: Across all
      studies, prasugrel's C(max) and AUC(0-t) were 51% and 42% lower in subjects with
      ESRD than in healthy subjects. AUC(0-t) did not differ between healthy subjects
      and subjects with moderate renal impairment. The magnitude of change and time
      course profiles of MPA was similar for healthy subjects compared with subjects
      with moderate renal impairment and those with ESRD. Prasugrel was well-tolerated
      in all subjects. CONCLUSION: There was no difference in pharmacokinetics or PD
      responses between subjects with moderate renal impairment and healthy subjects.
      Despite significantly lower exposure to prasugrel's active metabolite in subjects
      with ESRD, MPA did not differ between healthy subjects and those with ESRD.

PMID- 19744015
TI  - Attenuation of risperidone-induced hyperprolactinemia with the addition of
      aripiprazole.
AB  - Hyperprolactinemia can be a complication of conventional neurolepics as well as
      risperidone. We report the third case of attenuation of risperidone-induced
      hyperprolactinemia by aripiprazole.

PMID- 19744016
TI  - Acute cholestatic hepatitis induced by fenofibrate.
AB  - We report a case of acute liver injury probably due to fenofibrate. A 50-year-old
      female without a history of liver disease developed cholestatic hepatitis during
      her second week of fenofibrate treatment. Laboratory tests on admission showed
      serum bilirubin 534.0 mcmol/L (conjugated 444.0), alkaline phosphatase (AP) 8.76,
      gamma-glutamyl traspeptidase (GGT) 20.92, alanine aminotransferase (ALT) 2.6,
      aspartate aminotransferase (AST) 3.64 mckat/L. Fenofibrate withdrawal and
      ursodeoxycholic acid (750 mg daily) administration was rapidly followed by a
      favourable outcome.

PMID- 19744017
TI  - Tumor lysis syndrome after starting treatment with Gleevec in a patient with
      chronic myelogenous leukemia.
AB  - Chronic myelogenous leukemia (CML) is one of the myeloproliferative disorders. It
      accounts for 15-20% of all leukemias in adults. The mainstay of diagnosis is the
      detection of Philadelphia chromosome or one of its products. Tyrosine kinase
      inhibitors changed the paradigm of treating such disease with the good responses.
      However, they do have side effects. In our case we will report tumor lysis
      syndrome happening after starting Imatinib myselate. We did a literature review
      and looked all the cases that documented this complication.

PMID- 19744018
TI  - Guest Editorial: Nursing history and the articulation of power.

PMID- 19744019
TI  - Bertha Harmer's 1922 textbook - The Principles and Practice of Nursing: clinical
      nursing from an historical perspective.
AB  - AIMS AND OBJECTIVES: This study analyses the origins of a widely used textbook of
      nursing, commonly utilised in North American Schools of Nursing since 1922, and
      eventually worldwide. A biography of its first author, Bertha Harmer, is also
      included. BACKGROUND: Tracing central ideas of nursing throughout the various
      editions, the book provides a commentary on the cultural-historical context of
      nursing and reveals how nursing leaders conceptualised the day-to-day knowledge
      base nurses would need for their practice. DESIGN AND METHODS: Historical
      analysis. RESULTS: The core nursing concept of 'human needs' was central to
      Harmer's work and thinking. CONCLUSIONS: Its continuous development by her and
      her later co-author, Virginia Henderson, reflected broader changes in nursing
      that were central to the construction of nursing as hospital-based care during
      the twentieth century. RELEVANCE TO CLINICAL PRACTICE AND CONCLUSION: Renewal of
      nursing practice exists by the virtue of nurses' collective ability to question
      continuously and critically, the foundations of their practice. Historical
      analysis of core nursing concepts is one approach to further such critique.

PMID- 19744020
TI  - Conflict and costs when reforming nursing: the introduction of Nightingale
      nursing in Australia and Canada.
AB  - AIMS AND OBJECTIVES: To examine the financial impact of Nightingale nursing in
      the mid-19th century; to identify any long-term implications of this financial
      impact on nursing. BACKGROUND: Previous research into the transformation of mid
      19th century hospitals has suggested the importance of economic issues. We
      explore this issue from the perspective of the introduction of trained,
      Nightingale-style nursing. DESIGN: Historical methodology. METHODS: We use two
      examples, in Sydney (Australia) and Montreal (Canada), where there was a distinct
      break between older-style nursing and implementing of Nightingale nursing. We
      searched all relevant primary sources for data relating to on-going salary costs
      and staffing numbers. FINDINGS: We found runs of data to demonstrate the huge
      increase in staff numbers and salary expenses around the time of the introduction
      of Nightingale nursing at Sydney and Montreal General Hospitals. The one instance
      of declining costs was at Sydney Hospital during 1873-84. There, the salary
      expenditure on the bedside nurses fell as nursing probationers (students)
      undertook the bulk of the nursing. DISCUSSION AND CONCLUSIONS: The data available
      for Sydney and Montreal Hospitals supports the argument that Nightingale nursing
      and the demands of more effective medicine entailed a major jump in hospital
      costs. Given its expense, it is not surprising that conflict inevitably
      accompanied the introduction of Nightingale nursing. On the evidence of Sydney, a
      solution was found in hospital-based training schools with relatively poorly paid
      probationers. An on-going problem was that these schools functioned to contain
      nursing costs as much as to provide nursing instruction. IMPLICATIONS FOR
      CONTEMPORARY POLICY: While further study is needed, the two examples presented
      here suggest that nursing instruction in the past was a significant solution to
      the problem of increased hospital costs. An awareness of past solutions to on
      going problems may prevent similar sacrifice of nurses in our contemporary
      hospital crisis.

PMID- 19744021
TI  - 'I am willing to take the risk': politics, policy and the translation of the
      hospice ideal.
AB  - AIMS: To analyse the processes by which the hospice concept was translated into a
      reimbursable model of care in the USA and what was gained and what was lost in
      translation. BACKGROUND: Existing scholarship of the modern hospice movement
      typically focuses on the contributions of physicians to its inception and
      development. However, very little is known about the multifaceted role of nurses
      in the development of hospice care and the impact of Medicare policy on
      contemporary hospice care in the USA. DESIGN: Primary data were collected and
      interpreted using a blended social/policy history framework. METHODS: Archival
      data were drawn from the papers of individuals and organisations integral to the
      American hospice movement; Congressional testimony; and, primary and secondary
      research data and reports. Interviews with key individuals were taped and
      transcribed verbatim. Data were analysed for emergent patterns, themes and
      subthemes. These were then contextualised within historiographical framework of
      twentieth century healthcare reforms. RESULTS: Nurses were central to the
      inception and development of hospice care in the United States. While they were
      intricately involved with most aspects of the hospice movement and helped to
      frame the policy debate, they were ultimately unable to wholly determine national
      policy or extend their influence beyond their own circles. CONCLUSIONS: The
      standardisation of hospice care in the USA served to improve the quality of care
      for many dying patients and their families. Yet, it also served to reinforce a
      false dichotomy between care for the living and care for the dying. As a result,
      the integration of palliative care concepts into standard clinical nursing
      practice remains problematic. RELEVANCE TO CLINICAL PRACTICE: This study
      illuminates the socio-political complexities that shape health policy and the
      subsequent impact on nursing practice. Its findings have broad implications for
      contemporary palliative care initiatives regardless of locale.

PMID- 19744022
TI  - Bottom lines: the influence of government funding on 20th century district
      nursing practice in Australia.
AB  - AIMS AND OBJECTIVES: To investigate the impact of past government policy and
      legislation on the practice of district nursing in Australia. BACKGROUND: Nurses
      have historically been politically passive and have not engaged in the political
      processes of policy development. However, legislation can have profound impacts
      on the daily work of nurses as demonstrated in this paper. DESIGN: Historical
      analysis. METHODS: The archival records of six district nursing services in
      Australia were analysed within the political, social and economic context of the
      20th century, with particular focus on the 1950s and 1970s. RESULTS: Two pieces
      of Federal legislation passed in 1956 and 1973, respectively, had critical
      effects on the work of district nurses. Both resulted in significant expansion of
      district nursing in Australia; neither was formulated with input from district
      nursing services. However, together these acts shifted district nursing from
      being a voluntary, charity based activity to one that was greatly controlled by
      government. CONCLUSIONS: Greater government funding allowed district nursing to
      expand beyond the capacity possible when funding was locally based, but with
      government funding came other restrictions related to accountability processes
      and expectations regarding services provided, and these had profound effects on
      nursing practice, including excess workloads to the point of unsafe practice.
      RELEVANCE TO CLINICAL PRACTICE: Nurses need to engage with the political
      processes associated with government policy formulation and implementation if
      they are to avoid placing themselves and their clients in vulnerable situations
      as a result of government decisions.

PMID- 19744023
TI  - Counting nurses: the power of historical census data.
AB  - AIMS AND OBJECTIVES: This study used census data to construct a demographic
      profile of early 20th century nurses in the United States. BACKGROUND: Census
      data are recognised as a rich source of quantitative information on long-term
      changes. However, difficulties in retrieving census data dissuade researchers
      from exploiting this source. Integrated Public Use Microdata Series, a
      standardised and digitialised version of census data, enables greater ease in
      retrieving and analysing data. DESIGN AND METHODS: A sample of respondents
      identifying as 'professional nurses' for the years 1900-1950 was extracted from
      Integrated Public Use Microdata Series categorised by the variables of race, sex
      and marital status. The resulting data were analysed for simple frequency
      statistics using SPSS software. RESULTS: Results revealed a tremendous increase
      in the number of nurses over the five decades under study. Nurses were
      increasingly young, female, single and white until 1930. After 1930, white and
      African-American women nurses began to reflect trends towards more diversity.
      CONCLUSIONS: This study is the first systematic attempt to trace the demographic
      trajectory of professional nurses in the United States in the early 20th century.
      It also demonstrates the possibilities of using digital technologies to
      restructure the asking and answering of historical questions. The use of
      quantitative methods of social history has trans-national applications which can
      facilitate global investigations into the demographic composition of the nursing
      occupation. RELEVANCE TO POLICY: This way of using digitalisation of census data
      provides a way to examine historical trans-national workforce trends. Such trends
      provide a firmer base upon which to construct workforce and practice strategies
      for a future global workforce.

PMID- 19744024
TI  - Recruitment, retention and representation of nurses: an historical perspective.
AB  - AIMS AND OBJECTIVES: To demonstrate how an appreciation of the history of nursing
      can help towards an understanding of present problems and provide signposts for
      the future and to consider the recruitment of nurses in the context of their
      social and economic status past and present. BACKGROUND: In the twenty-first
      century, nursing has been subject to the gaze of the press and commentators
      evoking a lost golden age. A golden age when wonderful care was given by ideal
      young women and standards were upheld by matrons. History demonstrates that
      recruitment to nursing and their education has been the subject of comment by
      press and public through the twentieth century. DESIGN: Sources consulted:
      Newspaper articles commentating on contemporary nursing, secondary works on
      history of nursing, archival sources, government reports and historical journals
      and oral histories. METHODS: Analysis of archival sources and oral sources.
      Interrogating them against the historiography and building up the
      interconnectedness of what they reveal. RESULTS: Flawed but nevertheless
      influential reports led to a misrepresentation of nursing based on misconceptions
      rather than on evidence. The blame was laid, unfairly, on the system of nurse
      education and senior nurses. What lay at the heart of the recruitment crises was
      that demand for registered nurses exceeded supply. CONCLUSION: Commentators then
      as now tried to find simplistic answers rather than consider a range of factors
      contributing to the shortage of nursing. IMPLICATIONS FOR CONTEMPORARY
      PRACTICE/RELEVANCE TO CLINICAL PRACTICE: Nursing continues to compete in an
      overcrowded labour market. New approaches to recruitment have, contrary to
      popular perception, been successful in attracting outside its traditional labour
      pool. Having an awareness of the influences that have shaped the present can help
      nurses respond to polemic and misinformed opinion.

PMID- 19744025
TI  - 'When the city is a great field hospital': the influenza pandemic of 1918 and the
      New York city nursing response.
AB  - AIMS AND OBJECTIVES: To describe and analyse the nurses' role in responding to
      the influenza epidemic in New York City in 1918. BACKGROUND: Today the world is
      facing the threat of pandemic avian influenza and there is renewed interest in
      lessons learned from the influenza pandemic of 1918, one of the deadliest disease
      outbreaks recorded in history. Much of the published history has been written
      from a medical or military perspective. No comprehensive account of nursing's
      role has been written. DESIGN: A social history framework was used. METHODS:
      Traditional historical methods were used for data collection, data immersion, the
      development of a chronology and themes. Critical analysis of social, political
      and economic context was also done. Primary sources included the Lillian D. Wald
      papers at the New York Public Library, newspapers, journal articles and other
      archival data. RESULTS: In 1918, New York City nurses provided care to thousands
      of patients. They did so with minimal federal support, relying on local community
      agencies to establish makeshift hospitals and provide soup kitchens. The Henry
      Street Visiting Nurses, assisted by numerous social agencies and Red Cross
      volunteers, visited patients in their homes and provided them with the only
      treatment there was: nursing care. CONCLUSIONS: In 1918, immediate cooperation
      among a previously established network of nursing and other social organisations
      and prompt cooperation with the American Red Cross and the United States Public
      Health Service was essential to New York City's response to the crisis. RELEVANCE
      TO CLINICAL PRACTICE: Should an influenza pandemic occur today, as many as a
      billion people could fall ill. Shortages of antiviral drugs, the speed with which
      the pandemic could occur and its widespread effects are such that nursing, public
      health and medical professionals will need to rely on local personnel and
      supplies. Immediate cooperation and collaboration among federal, state and local
      organizations will be essential to the response.

PMID- 19744026
TI  - Supporting or sabotaging the surgeon's efforts: portrayals of the surgical
      nurse's role in preventing wound sepsis, 1895-1935.
AB  - AIMS AND OBJECTIVES: To examine the surgical nurse's role in preventing wound
      sepsis (infection) and how this was portrayed in nursing literature in the pre
      antibiotic period, 1895-1935. BACKGROUND: While the history of infection control
      in general has been researched for the mid-20th century, more detailed research
      is needed of the pre-antibiotic period, specifically of the surgical nurse's role
      in preventing wound sepsis. Closer examination is also warranted of the way the
      nurse's role was perceived in specific practice areas, such as surgeons' views of
      the surgical nurse's role. DESIGN: Historical research. METHODS: Analysis of
      historical British, Canadian, Australian and New Zealand nursing journals and
      British and Australian surgical nursing textbooks. RESULTS: Between 1895-1935
      skilled surgical nurses were valued as 'supporters' of the surgeon's heroic
      efforts, acting as diligent 'scrubbers' and vigilant 'sentries' to guard patients
      from microbial attack, yet tended to be blamed as 'saboteurs' and 'slovens' when
      wound sepsis occurred. The most noticeable changes in knowledge and practice
      related to greater use of sterilised dressing materials, less reliance on
      unnecessarily strong antiseptics, and less intensive methods in preparing
      surgical materials. CONCLUSIONS: Although the literature related the nurse's role
      to the surgeon rather than the patient, interpreting it merely as a subservient
      relationship would ignore the more complex portrayals evident in the literature.
      Surgeons looked for support rather than subservience, and a conscientious
      approach rather than obedience. RELEVANCE TO CLINICAL PRACTICE: This historical
      research shows nurses both the enduring nature of aspects of clinical knowledge
      and practice as well as the slow process of change in others. It reminds nurses
      of the danger of infection, the constant vigilance required and the measures
      needed when practising without antibiotics.

PMID- 19744027
TI  - Nursing in a therapeutic community: the Fulbourn experience, 1955-1985.
AB  - AIM: To explore the role of the mental health nurse in wards run on therapeutic
      community principles in one English provincial hospital. BACKGROUND: Under a
      pioneering Medical Superintendent, the restrictive regime for patients with
      mental health problems in Fulbourn Hospital was replaced by a new commitment to
      'social therapy'. Ward doors were unlocked, patients were encouraged to undertake
      work-based activities and finally the wards were reorganised on 'therapeutic
      community' principles. DESIGN: This study used oral history methods to supplement
      evidence from published sources. A total of 27 oral history interviews were
      conducted between 2003-2008 and these data were analysed in the context of
      documentary material from local archives. RESULTS: The establishment of wards at
      Fulbourn run on therapeutic community lines posed considerable challenges to the
      customary working practices of their mental health nurses. The two themes
      highlighted in this paper were the symbolic meaning of the abandonment of nursing
      uniforms in favour of casual clothing and the hospital authorities' preparedness
      to accept the risks associated with implementing the philosophy of the
      therapeutic community. CONCLUSIONS: Oral history has a unique role to play in
      recording the detailed aspects of nursing practice which are often difficult to
      reconstruct from documentary sources alone. RELEVANCE TO CLINICAL PRACTICE:
      Nurses played a key role in the transformation of the therapeutic milieu of
      Fulbourn Hospital and their experiences have relevance to current debates in
      mental health care.

PMID- 19744028
TI  - A challenge to nursing: an historical review of intellectual disability nursing
      in the UK and Ireland.
AB  - AIMS: The aim of this paper is to provide an account of the early development of
      what was originally known as 'mental deficiency' nursing in the UK and Ireland.
      BACKGROUND: After a brief review of research literature, it analyses key issues
      behind the development of a workforce positioned on the margins of nursing in the
      two jurisdictions through a comparative discussion of similarities and
      differences. DESIGN: The paper draws on two doctoral studies that examined the
      development of intellectual disability nursing using an historiographical design.
      METHODS: Primary sources consulted included records of nursing regulatory bodies,
      national archives, Royal College of Psychiatrists, archives, nursing journals,
      individual institutional records in both jurisdictions. RESULTS: In both
      countries, psychiatrists established early training programmes for nurses,
      although a nursing model was adopted to meet service needs in the 1950s.
      CONCLUSIONS: However, the way in which this branch of nursing developed laid the
      foundation for tensions as to whether it is appropriately located within the
      discipline of nursing. Ireland's colonial past and postcolonial position, the
      role of the church, welfare systems and diverse socio-political drivers for
      change represent key differences between the two jurisdictions. IMPLICATIONS:
      What eventually became known as learning or intellectual disability nursing poses
      a continued challenge for the profession as a whole in regard to its breadth,
      role and focus in working with marginalised groups in society. The paper
      considers the risks for UK and Irish intellectual disability nurses for
      marginalisation in nursing should they forge closer links to other disciplines
      concerned with common threads of disability, education or social care.

PMID- 19744029
TI  - 'The geriatric hospital felt like a backwater': aspects of older people's nursing
      in Britain, 1955-1980.
AB  - AIMS AND OBJECTIVES: The aim of this article is to examine the experiences of
      ward-level nurses who cared for older people in general hospitals between 1955
      1980. BACKGROUND: There is very little published on the history of older adult
      nursing and no recent material from the United Kingdom. There are, however, the
      works of Cecily Hunter in Australia and Erica Roberts in Canada. It is the
      intention of this study to contribute to this important area of research. DESIGN:
      This is an oral history project in which 20 nurses who had worked on older adults
      ward between 1955-1980 were interviewed. METHODS: All the interviews were taped,
      transcribed and data-themed. Ethical clearance for the project was obtained from
      the University Ethics Committee and all participants were anonymised. RESULTS:
      Many of the nurses found the experience very difficult, though there were
      exceptions. Several participants had worked on older adults ward during their
      training and then had never wanted to return. Most described a paucity of
      resources and longevity of staff on the wards. CONCLUSIONS: Using the
      sociological theory of Erving Goffman, this article introduces a novel method of
      understanding nursing history, although his ideas have been used in medical
      history. The value of his theories for this study is in the identification of
      nurses as being part of the same system as the patients themselves. IMPLICATIONS
      FOR CONTEMPORARY POLICY, RESEARCH AND/OR PRACTICE: For nurses to care effectively
      for their patients, nurses themselves must be valued. Subordination and
      regimentation tend to dehumanise the carers which, in turn, dehumanises the cared
      for.

PMID- 19744030
TI  - Commentary on Swallow V (2008) An exploration of mothers' and fathers' views of
      their identities in chronic-kidney-disease management: parents as students?
      Journal of Clinical Nursing 17, 3177-3186.

PMID- 19744031
TI  - Commentary on Lau-Walker MO, Cowie MR & Roughton M (2009) Coronary heart disease
      patients' perception of their symptoms and sense of control are associated with
      their quality of life three years following hospital discharge. Journal of
      Clinical Nursing 18, 63-71.

PMID- 19744032
TI  - Commentary on Crowe M, Inder M, Joyce P, Moor S, Carter J & Luty S (2009) A
      developmental approach to the treatment of bipolar disorder: IPSRT with an
      adolescent. Journal of Clinical Nursing 18, 141-149.

PMID- 19744033
TI  - Efficacy of four insect repellents against mosquito bites: a double-blind
      randomized placebo-controlled field study in Senegal.
AB  - Insect-borne diseases represent a worldwide threat. In addition to fight against
      vectors (insecticides) and disease prevention (vaccination against yellow fever,
      chemoprophylaxis against malaria), insect repellents applied on the skin could
      help reduce the heavy burden related to these diseases. In a field study
      performed in Senegal, we compared the efficacy of one skin application between 3
      and 4 p.m. of four spray repellents [icaridine 20%, para-menthane-diol (PMD) 20%
      and 50% and DEET 50%] against placebo, among 100 healthy male and female
      volunteers experienced with mosquito capture. Double-blind randomized cross-over
      placebo-controlled study (Latin-square design) during five consecutive nights (7
      p.m. to midnight) in two villages was conducted. To avoid residual effect, right
      or left leg was alternately exposed during consecutive nights and the exposed leg
      was washed before next night. The statistical model was random and mixed effects
      ANOVA. All four active repellents provided a significant and similar protection
      compared with placebo, lasting 8 h. However, there was a non-significant trend
      for a higher protection by DEET 50% than by PMD 20% (P = 0.07). Duration of
      protection was similar for all repellents. Their effects were similar among men
      and women, and against Anopheles or other species. No serious adverse drug
      reaction was noticed. Using a rigorous methodology and a large number of
      volunteers, our well-controlled study demonstrated an important and similar
      protective effect of all four repellents compared with placebo. Such field
      studies should be required before approval of any newly developed repellent.

PMID- 19744034
TI  - The relationship of the interleukin-6 -174 G>C gene polymorphism with
      cardiovascular risk factors in Turkish polycystic ovary syndrome patients.
AB  - We aimed to evaluate the relationship between 174 promoter region of the
      interleukin-6 (IL-6) C/G gene polymorphism and high sensitive C-reactive protein
      (hs-CRP), fibrinogen and carotis intima-media thickness (CIMT), body mass index,
      homeostatic model assessment (HOMA) insulin resistance index, serum lipid
      parameters, in polycystic ovary syndrome (PCOS) patients carrying a potential
      risk for developing cardiovascular disease (CVD). We studied 88 PCOS patients and
      119 healthy controls. PCOS was defined by the Rotterdam PCOS consensus criteria.
      The genotype IL-6 distribution did differ between the control group (CC 10.1%, GC
      63.0%, GG 29.6%) and the PCOS patients (CC 5.7%, GC 29.5%, GG 64.8%) (P < 0.001).
      The frequency of the polymorphic G allele was also no similar for the group with
      PCOS as for the control group with 79.5% and 58.4% respectively (P < 0.001). Both
      in PCOS patients and in control group, no statistically significant difference
      was determined between C/C, G/C and G/G, and blood cholesterol levels,
      triglyceride levels, high-density lipoprotein levels, low density lipoprotein
      levels, fasting blood sugar levels, insulin levels, HOMA values, CIMT
      measurements either on the right or left side, hs-CRP, f-testosterone, fibrinogen
      and 17 alpha-hydroxy-progesterone levels (P > 0.05). Gene polymorphism of IL-6 
      174 G>C is a risk factor for PCOS in Turkish patients, but we found no
      relationship between the cardiovascular risk factors and IL-6 -174 G>C gene
      polymorphism in women with PCOS and healthy subjects. Our negative results in
      risk factors of CVD can probably be explained by the fact that metabolic
      parameters and endothelial systems of patients may not yet be affected in this
      short time of period.

PMID- 19744035
TI  - Susceptibility of mice to invasive aspergillosis correlates with delayed cell
      influx into the lungs.
AB  - Ubiquitous fungus Aspergillus fumigatus (A. fumigatus) is involved in invasive
      pulmonary aspergillosis (IPA), a frequent infection in immunocompromized
      patients. Genetic differences are likely to play a role predisposing to IPA. This
      study was aimed to compare six genetically different mouse strains in their
      susceptibility to IPA and to determine possible mechanisms involved in the
      pathogenesis of this infection. Immunosuppressed BALB/c and C57BL/6 mice infected
      with A. fumigatus conidia were more resistant to IPA than DBA/1, DBA/2, CBA, and
      A/Sn strains. Phagocytosis of A. fumigatus conidia by blood polymorphonuclear
      neutrophils (PMN) or bone marrow derived dendritic cells showed no difference
      between strains. All IPA susceptible strains demonstrated decreased PMN influx
      into the lungs during infection compared with resistant strains. Flow cytometry
      analysis of the composition of lung infiltrating cells showed that IPA
      susceptible mice had a decreased number of phagocytes before the infection. After
      infection the numbers of Gr-1(+)CD11b(+) PMN cells in the lungs of
      immunosuppressed mice increased from 10-20% to 50-60% while the percentage of
      CD11(+)F4/80(+) resident macrophages was unchanged. Among susceptible strains
      DBA/2 and A/Sn have a defect in C5 component of complement. Injection of normal
      serum into complement deficient but not into complement sufficient CBA or DBA/1
      mice significantly improved their survival. We showed that complement replacement
      significantly increased PMN homing to the lungs of complement deficient mice.
      Thus, defect in complement system can predispose to IPA. Our results demonstrated
      that early influx of PMN into the lungs of mice is important for the resistance
      to IPA.

PMID- 19744036
TI  - Frequency of the CCR5-Delta32 polymorphism in the Maltese population at birth.
AB  - In this study, the frequency of the CCR5-Delta32 polymorphism was estimated in
      the human population of Malta. The frequency of the CCR5-Delta32 allele was found
      to be 1.1% which was similar to that of other island populations, and agree with
      the north to south gradient observed across Europe.

PMID- 19744039
TI  - Immunotherapy of diffuse gliomas: helping the brain fight back!

PMID- 19744038
TI  - Robust detection of EGFR copy number changes and EGFR variant III: technical
      aspects and relevance for glioma diagnostics.
AB  - Epidermal growth factor receptor (EGFR) is commonly affected in cancer, generally
      in the form of an increase in DNA copy number and/or as mutation variants [e.g.,
      EGFR variant III (EGFRvIII), an in-frame deletion of exons 2-7]. While detection
      of EGFR aberrations can be expected to be relevant for glioma patients, such
      analysis has not yet been implemented in a routine setting, also because feasible
      and robust assays were lacking. We evaluated multiplex ligation-dependent probe
      amplification (MLPA) for detection of EGFR amplification and EGFRvIII in DNA of a
      spectrum of 216 diffuse gliomas. EGFRvIII detection was verified at the protein
      level by immunohistochemistry and at the RNA level using the conventionally used
      endpoint RT-PCR as well as a newly developed quantitative RT-PCR. Compared to
      these techniques, the DNA-based MLPA assay for EGFR/EGFRvIII analysis tested
      showed 100% sensitivity and specificity. We conclude that MLPA is a robust assay
      for detection of EGFR/EGFRvIII aberrations. While the exact diagnostic,
      prognostic and predictive value of such EGFR testing remains to be seen, MLPA has
      great potential as it can reliably and relatively easily be performed on
      routinely processed (formalin-fixed, paraffin-embedded) tumor tissue in
      combination with testing for other relevant glioma markers.

PMID- 19744040
TI  - Immunotherapy of diffuse gliomas: biological background, current status and
      future developments.
AB  - Despite aggressive multimodal treatment approaches, the prognosis for patients
      with diffuse gliomas remains disappointing. Glioma cells often extensively
      infiltrate in the surrounding brain parenchyma, a phenomenon that helps them to
      escape surgical removal, radiation exposure and chemotherapy. Moreover,
      conventional therapy is often associated with considerable local and systemic
      side effects. Therefore, the development of novel therapeutic approaches is
      essential to improve the outcome of these patients. Immunotherapy offers the
      opportunity to specifically target residual radio-and chemoresistant tumor cells
      without damaging healthy neighboring brain tissue. Significant progress has been
      made in recent years both in understanding the mechanisms of immune regulation in
      the central nervous system (CNS) as well as tumor-induced and host-mediated
      immunosuppression elicited by gliomas. In this review, after discussing the
      special requirements needed for the initiation and control of immune responses in
      the CNS, we focus on immunological phenomena observed in glioma patients, discuss
      different immunological approaches to attack glioma-associated target structures
      and touch on further strategies to improve the efficacy of immunotherapy of
      gliomas.

PMID- 19744041
TI  - Dendritic cell therapy of high-grade gliomas.
AB  - The prognosis of patients with malignant glioma is poor in spite of multimodal
      treatment approaches consisting of neurosurgery, radiochemotherapy and
      maintenance chemotherapy. Among innovative treatment strategies like targeted
      therapy, antiangiogenesis and gene therapy approaches, immunotherapy emerges as a
      meaningful and feasible treatment approach for inducing long-term survival in at
      least a subpopulation of these patients. Setting up immunotherapy for an inherent
      immunosuppressive tumor located in an immune-privileged environment requires
      integration of a lot of scientific input and knowledge of both tumor immunology
      and neuro-oncology. The field of immunotherapy is moving into the direction of
      active specific immunotherapy using autologous dendritic cells (DCs) as vehicle
      for immunization. In the translational research program of the authors, the whole
      cascade from bench to bed to bench of active specific immunotherapy for malignant
      glioma is covered, including proof of principle experiments to demonstrate
      immunogenicity of patient-derived mature DCs loaded with autologous tumor lysate,
      preclinical in vivo experiments in a murine orthotopic glioma model, early phase
      I/II clinical trials for relapsing patients, a phase II trial for patients with
      newly diagnosed glioblastoma (GBM) for whom immunotherapy is integrated in the
      current multimodal treatment, and laboratory analyses of patient samples. The
      strategies and results of this program are discussed in the light of the
      internationally available scientific literature in this fast-moving field of
      basic science and translational clinical research.

PMID- 19744043
TI  - 6-year-old girl with hydrocephalus.
AB  - With rare exceptions, pediatric tectal gliomas have been generally reported as
      low-grade tumors with relatively good prognosis. The patients are usually treated
      conservatively to manage the signs and symptoms of obstructive hydrocephalus. We
      report a case of a tectal glioma in a 6-years-old girl with histological features
      of anaplastic mixed oligoastrocytoma that continues to progress despite
      chemotherapy and radiation therapy.

PMID- 19744042
TI  - EGFRvIII-targeted vaccination therapy of malignant glioma.
AB  - Given the highly infiltrative growth pattern of malignant glioma and the lack of
      specificity associated with currently available treatment regimens, alternative
      strategies designed to eradicate cancer cells while limiting collateral toxicity
      in normal tissues remain a high priority. To this end, the development of
      specific immunotherapies against targeted neoplastic cells represents a promising
      approach. The epidermal growth factor receptor class III variant (EGFRvIII), a
      constitutively activated mutant of the wild-type tyrosine kinase, is present in a
      substantial proportion of malignant gliomas and other human cancers, yet
      completely absent from normal tissues. This receptor variant consists of an in
      frame deletion, the translation of which produces an extracellular junction with
      a novel glycine residue, flanked by amino acid sequences that are not typically
      adjacent in the normal protein. In this review, both preclinical and early
      clinical development of a peptide vaccine directed against this portion of the
      EGFRvIII antigenic domain are recapitulated. Following vaccination, our group has
      demonstrated potent, redirected cellular and humoral immunity against cancer
      cells expressing the mutant receptor without significant toxicity. Additionally,
      the corresponding therapeutic outcomes observed in these studies lend credence to
      the potential role of peptide-based vaccination strategies among emerging
      antitumor immunotherapies in patients with malignant glioma.

PMID- 19744044
TI  - 22-year-old girl with status epilepticus and progressive neurological symptoms.
AB  - A 22-year-old girl presented with convulsive status epilepticus and a previous
      history of recurrent seizures, myoclonus, ataxia and impaired cognitive
      functions. Neurological examination revealed rest and action-induced myoclonus,
      pyramidal signs and opposition hypertonia. Testing revealed severe metabolic
      acidosis, elevated transaminases and creatine kinase, and respiratory
      insufficiency. After intubation and ventilation, thiopental was introduced but
      the patient's condition worsened dramatically with death in a few hours. Autopsy
      showed profuse periodic acid-Schiff (PAS) positive intracellular inclusions in
      the CNS (Lafora bodies), most abundant in thalamus, cerebellum, and brainstem, as
      well as in other organs. Genetic testing revealed a homozygous missense mutation
      (c.205C > G, P69A) in the EPM2B (NHLRC1) gene, confirming the diagnosis of
      progressive myoclonic epilepsy Lafora-type.

PMID- 19744045
TI  - A 76-year-old man with cognitive and neurological symptoms.
AB  - A 76-year-old man presented with cognitive symptoms, followed by headache and
      weakness of the lower limbs and left arm. The clinical course was progressive but
      fluctuating. On magnetic resonance imaging (MRI), a contrast-enhancing lesion 1
      cm in diameter was seen in the left temporal lobe. This lesion became attenuated
      and a new contrast-enhancing lesion 1 x 2 cm was seen in the left frontal lobe on
      a subsequent MRI. Following additional tests, treatment with corticosteroids for
      presumptive neurosarcoidosis was started, however, he soon expired. At autopsy,
      there was a tumor-like mass in the left frontal lobe. Pathologic evaluation
      revealed a primary T-cell lymphoma of the central nervous system (CNS). CNS T
      cell lymphomas may be difficult to diagnose, even histologically, due to their
      frequent small cell morphology and lack of significant atypia.

PMID- 19744046
TI  - A 22-year-old man with intracraneal hypertension and impaired sensation over the
      perineum and left foot.
AB  - Primary leptomeningeal tumors are rare and can have multiple origins. This young
      man presented an intracranial hypertension syndrome and brain MRI features of
      diffuse leptomeningeal enhancement over cerebral and cerebellar hemispheres. A
      second cerebellar biopsy allowed the diagnosis of a primary diffuse
      leptomeningeal Primitive Neuroectodermal Tumor (PNET). Besides the paucity of
      reports of primary leptomeningeal PNET, its differentiation from primary
      leptomeningeal medulloblastomas is not always clear-cut and is discussed.

PMID- 19744047
TI  - A 47-year old male with a cerebellopontine angle tumor.
AB  - A 47-year old man presented with a five-year history of fluctuating hearing
      impairment in the left ear. There was no tinnitus or vertigo. Imaging studies
      demonstrated a contrast-enhancing cerebellopontine angle mass in the left
      internal auditory canal. Surgically the lesion was attached to the cochlear
      nerve. Pathological evaluation revealed what is best described as an
      angiolipomatous hamartoma of the cochlear nerve. Similar lesions have only rarely
      been described.

PMID- 19744048
TI  - A 58 year old woman with a corpus callosum nodule at autopsy.
AB  - Intracranial lipomas are uncommon benign mesenchymal tumors, found usually near
      or at the midline. The existence of such intracranial tumors has been documented
      in the literature in only over 200 cases. Although usually asymptomatic, they can
      sometimes trigger neurological symptoms, specifically epileptic seizures. We
      describe the incidental finding of a lipoma of the corpus callosum at autopsy in
      a 58 year-old woman with a history of seizures, and provide a concise review of
      the pertinent literature with respect to this entity.

PMID- 19744049
TI  - Re: Diffuse leptomeningeal glioneuronal tumors: a new entity?

PMID- 19744052
TI  - A call for the reporting of effect sizes in research reports to enhance critical
      appraisal and evidence-based practice.

PMID- 19744053
TI  - Credibility of a meta-analysis: evidence-based practice concerning soy intake and
      breast cancer risk in premenopausal women.
AB  - PURPOSE: To report the findings from a critical appraisal concerning the
      credibility of a meta-analysis (M-A) about the role of dietary soy intake in
      reducing breast cancer risk. The use of an evidence-based, advanced nursing
      practice framework was used to appraise the M-A. APPROACH: The clinical question
      was developed from a problem that could be encountered in clinical practice. For
      premenopausal women, does the use of high dietary soy intake reduce the future
      risk of breast cancer compared with low dietary soy intake? A search of
      electronic databases yielded one M-A, which was selected to answer the question.
      FRAMEWORK: A framework was developed from various authors' work and used to
      appraise the M-A and guide implementation of the evidence-based practice (EBP)
      process. CONCLUSIONS: The findings of the M-A were not deemed credible because of
      deficient information regarding the target population and outcome variable, lack
      of confounder control, unclear inclusion and exclusion criteria of the sample,
      and invalid methods of data abstraction. Because the findings were not credible,
      they were deemed not to be clinically applicable. Therefore, a high soy diet
      would not necessarily be recommended.

PMID- 19744054
TI  - Evidence-based education and nursing pressure ulcer prevention textbooks: does it
      match?
AB  - BACKGROUND: The education of nurses has influenced the way of nursing practice
      for a long time. Nurse educators are required to offer up-to-date educational
      material, and textbooks are the most frequently used sources of knowledge during
      a nurse's education. AIM: In this study, researchers investigated the extent to
      which textbooks were evidence based regarding preventing pressure ulcers and
      knowing what recommendations to make for nursing students and publishers of
      nursing textbooks. METHOD: Educators at nursing schools in Germany were contacted
      by telephone to identify the most often used nursing textbooks. The
      recommendations of the German Expert Standard of Pressure Ulcer Prevention were
      compared with the content of the textbooks in a content analysis. Additionally,
      teachers were asked what additional material they were using to help prepare
      lectures. RESULTS: Only one of the four analysed textbooks complied with the
      recommendations of the German Expert Standard. Contents of the other books were
      incomplete. The authors of some books did not mention any up-to-date scientific
      evidence. The teachers often used additional material such as the German Expert
      Standard and research articles to prepare their lectures. DISCUSSION: German
      nursing textbooks were classified into research-based and authoritative texts.
      Because of the fast development and availability of research findings, one
      recommendation is that new forms of "textbooks" such as CD ROMs should be
      considered.

PMID- 19744055
TI  - Getting evidence into practice-understanding knowledge translation to achieve
      practice change.

PMID- 19744057
TI  - The role of intrusive and other recent life events on symptomatology in relapses
      of schizophrenia: a community nursing investigation.
AB  - This study aimed to identify the impact of life events on psychotic relapse in
      individuals with an established diagnosis of schizophrenia to explore their
      proneness to experience life events, to examine if any effect of life events was
      cumulative or triggering in nature and to explore if specific types of events
      influence subsequent symptom formation. An association between adverse life
      events and relapse in people with schizophrenia has been reported in several
      studies; however, the nature of the association remains unclear. Some studies
      suggest that intrusive events promote the formation of paranoid psychotic
      symptoms. Using well-validated semi-structured interview schedules the author
      interviewed participants during or shortly after relapse. The severity and
      intrusiveness of life events was rated and relationships between events and
      symptoms were explored. Increasing numbers of patients experienced life events
      especially moderately threatening life events in the last 4 weeks prior to
      relapse; however, no relationship was discovered between life events in general
      or specifically intrusive life events and the specific content of psychotic
      symptoms. An increased frequency of milder life events occurred in the 2 months
      prior to relapse, suggesting that chronic illness is not associated with absence
      of mild or moderately severe life events or with diminished sensitivity to them.

PMID- 19744058
TI  - Awareness of early warning signs and help-seeking behaviours among patients with
      schizophrenia who utilize social rehabilitation facilities in Japan.
AB  - The purpose of this study was to examine the relationship between early warning
      signs (EWS) and early help-seeking behaviours (HSB) and to identify the
      characteristics of patients with schizophrenia who sought early help. A cross
      sectional study was carried out in 2004 using a self-reported questionnaire.
      Participants were recruited from social rehabilitation facilities for the
      mentally ill; 224 subjects participated, 170 of whom had schizophrenia. The
      survey included questions about demographic characteristics, self-care behaviours
      (HSB, recognition of EWS and others) and current service utilization and
      satisfaction. Fisher's exact test and Student's t-test were used to compare the
      characteristics of study participants. Logistic regression analyses were used to
      examine the association between recognition of EWS and early HSB.We found that 96
      (56.5%) of 170 patients with schizophrenia reported at least one occasion of
      early HSB during their deterioration. Early HSB were related to the following
      factors: recognition of EWS, consultation with non-professional and professional
      support persons during deterioration, consulting with public mental health
      workers and living with family. Care and support should be offered to patients
      with schizophrenia to enable them to recognize their own mental deterioration.

PMID- 19744059
TI  - Epiphanies and research in the field of mental health.
AB  - In this paper I will argue that investigating our professional experiences can
      enrich our understanding, widen our perspective, transform our inner lives and
      create an endless source of discovery about ourselves, society and the
      professional discursive systems that we inhabit. I will call such events, after
      Denzin's work in 1989, epiphanies. In order to develop the theme I will give an
      account of my own experience of two such epiphanies on a psychoanalytic training
      course in counselling. I will then present my reflexive analysis of these events
      over the years, including my reflections on the peer review comments for this
      paper, and finish with some questions arising out of the study relating to the
      current status of nursing as an academic profession.

PMID- 19744060
TI  - The nurse and the use of narrative: an approach to caring.
AB  - The use by the nurse of the principles of narrative therapy to help patients re
      author their personal narrative, and change it from a problem-saturated story to
      one that is more preferred, is explored. Three main narrative techniques:
      deconstruction, externalization and re-authoring are described. Examples of these
      techniques are provided to help nurses at all levels of nursing practice assume
      the role of collaborator in the re-authoring process.

PMID- 19744061
TI  - Families' experiences of interaction with the public health nurse at the child
      health clinic in connection with mother's post-natal depression.
AB  - The birth of a new family member causes many changes in the way a family
      functions. Annually some 10% of mothers giving birth suffer from post-natal
      depression. This depression affects the mother herself, the baby and the
      functioning of the entire family. The healthcare personnel are faced with an
      important task in supporting the family in the course of changes occasioned by
      the birth of a baby. According to earlier studies, families with small children
      are fairly satisfied with the service provided by the child health clinics. The
      purpose of the present study was to form a theory of interaction with the public
      health nurse in the child health clinic when the mother is suffering from post
      natal depression from the viewpoint of family. The data for the study were
      gathered by interviewing nine families (nine mothers and five fathers) where the
      mother had displayed symptoms of post-natal depression. The data were analysed
      using continuous comparative analysis of grounded theory. The concepts of the
      theory emerged as a lack of continuing relationship, a need to be equal partners,
      a lack of individuality and a lack of family care. The relationships between
      categories were lack of discussing, lack of being confidential and lack of
      getting help enough. The core category emerging was lack of holistic cooperation
      with unique family. In spite of the emphasis placed on family centeredness in the
      operating principles of the work in child health clinics, its implementation in
      practical work cannot be taken for granted. Because of the limited resources
      available to the clinics, it is the experience of depressed mother in particular
      that they are not treated sufficiently as individuals and that they are subjected
      to adjudication in the clinics. The parents felt that the personality of the
      public health nurse was crucial to how they felt about the service they obtained
      from the clinic.

PMID- 19744062
TI  - Depression: a psychiatric nursing theory of connectivity.
AB  - This paper presents a theory of connectivity, which was formulated from the
      findings of a Classical Grounded Theory study that was designed to capture a
      sample of people's perceptions of living with depression or caring for
      individuals with depression. Data were collected from: (1) a focus group
      consisting of people with depression (n = 7), of which five were patients in the
      community and two were nurses; (2) one-to-one interviews with patients in the
      community (n = 5) and nurses (n = 5), three of whom had experienced depression
      from both sides of the caring process; and (3) two 'happy accident' focus groups
      (n = 25; n = 18) comprising of healthcare workers with a shared understanding of
      depression. Purposeful sampling was used initially. Thereafter, in keeping with
      one of the key tenets of grounded theory, theoretical sampling was used until
      theoretical saturation occurred. Data were analysed using the constant
      comparative approach together with the NVivo qualitative analysis software
      package. The core category that emerged was 'connectivity' relating to the
      connections and disconnections, which people make in their lives. Six key
      categories emerged all of which were integrated with the core category. Hence,
      connectivity provided a significant platform for understanding and responding to
      the life experience of depression. They were: (1) life encounters on the journey
      to naming; (2) depression: What's in a name? The silent thief; (3) tentative
      steps to health care; (4) connective encounters and challenges; (5) connecting
      with self; and (6) self-connection maintenance. Subsequently, a theory,
      'Depression: a psychiatric nursing theory of connectivity', surfaced from the
      overall findings. We argue that this theory of connectivity provides a framework
      that people working in the field of holistic treatment and care could use to
      better understand and respond to the life experience of people living with
      depression.

PMID- 19744063
TI  - The life circumstances of persons with a psychiatric disability: a survey in a
      region in southern Sweden.
AB  - This article describes the life circumstances of persons with a psychiatric
      disability living in one urban and six rural areas in a single region in Sweden.
      Furthermore, the life circumstances of persons with a psychiatric disability are
      discussed in relation to the aims of social policies in Sweden. Data were
      collected by means of a survey study exploring the formal support provided by
      local authorities to its citizens and the informal support given by family
      members and volunteers. The results reveal how the respondents themselves
      describe their life circumstances in terms of their living conditions, occupation
      and activities, health, and formal and informal support. The results indicate
      that persons with a psychiatric disability, regardless of where they live, need
      both formal and informal support in order to cope with their everyday lives. The
      family plays an important role in this, and it is essential for the formal and
      informal support systems to cooperate with each other. The lack of activities and
      opportunities for work experienced by persons with a psychiatric disability
      indicates that the sociopolitical goal of fostering access to employment and work
      and to earning a living for this group is far from having been attained.

PMID- 19744064
TI  - Manual restraint of adult psychiatric inpatients: a literature review.
AB  - Relatively little is known about the prevalence of manual restraint to manage
      violent or challenging behaviour in hospital psychiatric services or the
      circumstances of its use. This review identified 45 empirical studies of manual
      restraint of adult psychiatric inpatients, mostly from the UK. On average, up to
      five episodes per month of manual restraint might be expected on an average 20
      bed ward. Episodes last around 10 min, with about half involving the restraint of
      patients on the floor, usually in the prone position. Manually restrained
      patients tend to be younger, male and detained under mental health legislation.
      Staff value restraint-related training, but its impact on nursing practice has
      not been evaluated. Research has tended to focus on official reports of violent
      incidents rather than manual restraint per se. Larger and more complex studies
      are needed to examine how manual restraint is used in response to different types
      of incident and in different service settings.

PMID- 19744065
TI  - Eugenics by the back door? The unintended consequences of restricting people's
      choices about mental health medicines.

PMID- 19744066
TI  - Mental health inequalities and mental health nursing.
AB  - Reducing inequalities in health, including mental health, is of high priority in
      many national policies. However, it is not yet known how mental health nurses
      might respond to these policies. Using examples from the available evidence, we
      argue that the causes of mental health inequalities are complex and thought to
      arise from fundamental divisions in society. These divisions are formed by social
      relationships, which are influenced by deep social structures, such as the
      economy or culture. The extensive range of social determinants means that there
      is no single explanation of why inequalities in mental health might occur. It
      also suggests that these determinants may act synergistically to create pockets
      of inequity where health needs are most complex. This poses difficult challenges
      for mental health nurses who undoubtedly have a key role in addressing mental
      health inequalities, although their role is likely to be restricted to service
      redesign and delivery. Mental health nurses are unlikely to address some of the
      deeper structural determinants of mental health inequalities, such as poverty,
      which can only be tackled through government-led reforms. Furthermore, we must be
      mindful of the possibility that services offered by mental nurses may have an
      uneven uptake across social classes, which in turn could serve to maintain or
      worsen mental health inequalities. Therefore, a key question for mental health
      nursing, policy and training is whether these limitations are clearly recognized.

PMID- 19744070
TI  - The value of serum adipokine measurement in non-alcoholic fatty liver disease.

PMID- 19744071
TI  - The haplotype of the MxA gene promoter is associated with hepatitis B virus
      infection in a Chinese population.
AB  - BACKGROUND/AIM: The Myxovirus resistance protein A gene (MxA) is a key component
      of the innate antiviral response and has previously been shown to inhibit several
      viruses. This study was designed to assess whether the haplotype in the MxA
      promoter region was associated with hepatitis B virus (HBV) infection in a
      Chinese population. METHODS: Three hundred and twelve HBV-infected patients and
      317 healthy volunteers were enrolled in this study. Two polymorphisms of -88 and 
      123 located in the MxA gene promoter were identified by the polymerase chain
      reaction-restriction fragment length polymorphism method. RESULTS: The individual
      possessing haplotype GA, which was constructed by the two polymorphisms of -88G
      and -123A in the MxA gene promoter, was significantly associated with HBV
      infection [possessing one copy odds ratio (OR)=1.69, 95% confidence interval (CI)
      1.21-2.35; two copy OR=2.84, 95% CI 1.12-7.21 respectively]. CONCLUSIONS: This
      case-control study suggested that the haplotype GA in the MxA gene promoter
      region would increase the susceptibility to HBV infection in a Chinese
      population.

PMID- 19744074
TI  - Abstracts of ASCIA 2009, the 20th Annual Scientific Meeting, Australasian Society
      of Clinical Immunology and Allergy. September 16-18, 2009. Adelaide, South
      Australia, Australia.

PMID- 19744075
TI  - Murray et al. (2004) revisited: is bipolar disorder identical to schizophrenia
      without developmental impairment?

PMID- 19744076
TI  - Invited comment.

PMID- 19744081
TI  - Abstracts of the 2009 Annual Meeting of the German Clinical Pharmacologists.
      October 21-24, 2009. Heidelberg, Germany.

PMID- 19744082
TI  - Isokinetic and isometric muscle strength in a healthy population with special
      reference to age and gender.
AB  - AIM: Muscle strength is an excellent indicator of general health when based on
      reliable measurements. Muscle strength data for a healthy population are rare or
      non-existent. The aim of the present study was to measure a set of normal values
      for isometric and isokinetic muscle strength for all the major joint movements of
      the body and, from these data, to create a basis for comparison of the muscle
      strength of an individual with the expected value in a normal population.
      METHODS: A randomly selected group, aged 20-80 years, from the Copenhagen City
      Heart Study were studied. The group was subgrouped according to age and gender.
      Isometric and isokinetic muscle strength was measured in each subject across the
      main joints in the body. A statistical model was developed that encompassed the
      three main muscle groups: upper limbs, trunk and lower limbs. RESULTS: Muscle
      strength in healthy men decreases in a linear fashion from the age of 25 years
      down to between 54% and 89% at the age of 75 years, and seems not highly
      dependent on any other parameter than age. For women, the muscle strength is
      dependent on weight and is only related to age from around 40 years of age. The
      decrease in muscle strength from the age around 40 to 75 years is 48-92%. For
      most muscle groups, men are 1.5-2 times stronger than women, with the oldest men
      having strength similar to that observed among the youngest women. CONCLUSION: We
      developed a model to compare the isometric and isokinetic muscle strength of all
      the major joint movements of an individual with values for a healthy man or woman
      at any age in the range of 20-80 years. In all age groups, women have lower
      muscle strength than men. Men's muscle strength declines with age, while women's
      muscle strength declines from the age of 41 years.

PMID- 19744083
TI  - Abstracts of the AABB Annual Meeting and TXPO. October 24-27, 2009. New Orleans,
      Louisiana, USA.

PMID- 19744085
TI  - Mind to care. Abstracts of the 35th International Mental Health Nursing
      Conference of the Australian College of Mental Health Nurses. September 29
      October 2, 2009. Sydney, New South Wales, Australia.

PMID- 19744084
TI  - Abstracts of the International Veterinary Emergency Critical Symposium. Chicago,
      Illinois,USA. September 9-13, 2009.

PMID- 19744086
TI  - Cardiac vagal activity following three intensities of exercise in humans.
AB  - SUMMARY: Cardioprotective benefits of exercising at vigorous intensities are
      known, but reservations remain in prescribing such activity to the untrained
      population, due to a perceived risk of cardiac events. Few studies have
      investigated the recovery of the autonomic nervous system (ANS) after a single
      exercise bout, especially following vigorous exercise in healthy, young but
      untrained individuals. In this study, the recovery of the ANS, in particular
      indices of vagal activity were measured postexercise, at three intensities
      similar to current international recommendations for health. Thirteen individuals
      (six females, 22.2 +/- 3.1 years) performed three 20-min constant load tests
      lying supine on a modified bicycle ergometer at the following intensities:
      moderate (2 mmol l(-1) blood lactate concentration, BLC); hard (3 mmol l(-1)BLC);
      and vigorous (4 mmol l(-1)BLC) as derived from a maximal test. ECG data were
      collected during 5-min epochs at baseline then at: 5, 15, 30, 45 and 65-min
      postexercise. Heart rate variability (HRV) analysis was performed to obtain R-R
      interval, standard time [root mean square of successive differences (RMSSD)] and
      frequency measures [natural logarithm of high (lnHF) and low frequency (lnHF)].
      RMSSD, lnHF, lnLF and total power were reduced 5-min postexercise following all
      three intensities (P<0.01). Decreases persisted up to 15-min postexercise
      following hard and vigorous exercise only (P<0.01). In untrained young adults,
      parasympathetic reactivation is reduced up to 5-min postexercise regardless of
      intensity, returning to baseline by 30 min even after vigorous exercise. In this
      population, the benefits of exercise outweigh any risks of cardiac events that
      may be evoked by a reduction in the influence of vagal activity.

PMID- 19744087
TI  - Adaptative or maladaptative hypertrophy, different spatial distribution of
      myocardial contraction.
AB  - SUMMARY BACKGROUND: Left ventricular hypertrophy (LVH) may be an adaptative
      remodelling process induced by physical training, or result from pathological
      stimuli. We hypothesized that different LVH aetiology could lead to dissimilar
      spatial distribution left ventricular (LV) contraction, and compared different
      components of LV contraction using 2-dimensional (2-D) speckle tracking derived
      strain in subjects with adaptative hypertrophy (endurance athletes),
      maladaptative hypertrophy (hypertensive patients) and healthy controls. METHOD:
      We enrolled 22 patients with essential hypertension, 50 endurance athletes and 24
      healthy controls. All subjects underwent traditional echocardiography and 2-D
      strain evaluation of LV longitudinal, circumferential and radial function. LV
      basal and apical rotation and their net difference, defined as LV torsion, were
      evaluated. RESULTS: LV wall thicknesses, LV mass and left atrium diameter were
      comparable between hypertensive group and athletes. LV longitudinal strain was
      reduced only in hypertensive patients (P < 0.05). LV apex circumferential strain
      was higher in hypertensive patients than in other groups (P < 0.001), LV basal
      circumferential strain, although slightly increased, did not reach significant
      difference. Hypertensive patients showed significantly increased rotation and
      torsion (P < 0.001), while no differences were observed between athletes and
      control. CONCLUSION: In patients with pathological LVH, LV longitudinal strain
      was reduced, while circumferential deformation and torsion were increased. No
      differences were observed in LV contractile function between subjects with
      adaptative LVH and controls. In pathological LVH, increasing torsion could be
      considered a compensatory mechanism to counterbalance contraction and relaxation
      abnormalities to maintain a normal LV output.

PMID- 19744088
TI  - Measurement of physical work capacity in patients with chronic aortic
      regurgitation: a potential improvement in patient management.
AB  - BACKGROUND: Timing of surgery in aortic regurgitation (AR) is important. Exercise
      testing is recommended upon uncertainty about functional limitations but reports
      on cardiopulmonary exercise testing (CPET) in populations with pure chronic AR
      are scarce. METHOD: Twenty-eight patients referred for surgery because of chronic
      AR (13 in NYHA I, 10 in NYHA II and five in NYHA III) were tested by CPET pre-
      and 6 months postoperatively. Echocardiography, with measurement of left
      ventricular ejection fraction (LVEF), diameters (LVED, LVES) and volumes (LVEDV,
      LVESV) was also performed. RESULTS: The patients had normal LVEF pre- and
      postoperatively. LV diameters and volumes diminished significantly
      postoperatively (LVED from 67 to 57, LVES from 49 to 41 mm; P < 0.001). The
      majority of the patients had a 'low' physical work capacity, none of them
      performed better than 'average' according to Astrand's classification
      preoperatively and there was no significant postoperative improvement. The mean
      peak oxygen uptake (VO(2peak)) was 25 ml kg(-1) min(-1) both pre- and
      postoperatively, and six of the 28 patients had a VO(2peak) of less than 20 ml
      kg(-1) min(-1). VO(2peak) was not significantly related to NYHA class.
      CONCLUSION: LVEF, diameters and volumes at rest did not fulfil the criteria for
      surgery in most of our AR patients, of whom 46% were asymptomatic. However, many
      had a remarkably low work capacity, which was neither improved 6 months
      postoperatively nor correlated to echocardiographic LV dimensions. CPET predicted
      the postoperative work capacity and may, therefore, be a useful complement for
      timing of surgery in patients with chronic AR.

PMID- 19744089
TI  - Long-term results after conversion from calcineurin inhibitors to sirolimus in
      renal transplant patients.
AB  - BACKGROUND: Calcineurin inhibitors (CNI) toxicity is one of the contributing
      factors for the development and progression of chronic allograft dysfunction
      (CAD). Conversion to sirolimus (SRL) from CNI improves renal function kidney in
      transplant recipients. METHODS: A retrospective review from patients abruptly
      converted from CNI to SRL over a three yr period is reported. RESULTS: Thirty
      nine patients were converted 55.2+/-58 months after renal transplantation. 24
      month patient and graft survival was 100% and 92%. Acute rejection incidence was
      7.6%. Overall, serum creatinine (SCr) and Cockcroft-Gault creatinine clearance
      (CGCrCl) improved. In responders, SCr improved from 2.48+/-0.8 to 1.94+/-0.8
      mg/dL (p<0.05) CGCrCl improved from 37.8+/-17.4 to 51.9+/-23.8 mL/min at two
      years. An increase in proteinuria was observed from conversion to month 12 in
      responders (189.4+/-512.8 to 488.3+/-890.6 mg/day, p<0.05) and from conversion to
      month six in non-responders (1179.4+/-2001.1 to 2357+/-4172.9 mg/day, p<0.05).
      Low proteinuria had positive predictive value for renal response after
      conversion. CONCLUSION: Conversion from CNI to SRL with CAD is associated with
      improved renal function with an increase in proteinuria. Low proteinuria is a
      possible positive predictive factor for successful conversion.

PMID- 19744090
TI  - Differences in perceived health status between kidney transplant recipients and
      dialyzed patients are based mainly on the selection process.
AB  - Kidney transplantation offers longer survival, less morbidity and lower costs
      than dialysis. It is also believed to improve quality of life. The aim of this
      study was to compare prospectively the perceived health status (PHS) of dialyzed
      patients on a waiting list with kidney transplant recipients after
      transplantation, matched for age, gender and comorbidity. The sample consisted of
      93 dialyzed patients on a waiting list for deceased-donor kidney transplantation
      and 87 incident transplant recipients. A total of 62 dialyzed patients were
      matched for age, gender and comorbidity with 62 transplant recipients. PHS was
      measured using the SF-36 questionnaire. Data from baseline and after 12 months
      were compared between the groups. Patients on dialysis had worse physical (49 +/-
      21) and mental (59 +/- 18) PHS than transplant recipients (56 +/- 21 and 64 +/-
      18, p < or = 0.05), but when matched pairs were compared, no differences in PHS
      were found. After 12 months, PHS did not change significantly in either group.
      The PHS of patients after kidney transplantation is better than that of those on
      dialysis. However, this fact is significantly influenced by the selection
      procedure, as only some dialyzed patients are put onto the waiting list while
      others were actually transplanted. The differences disappear with matching.

PMID- 19744091
TI  - German citizens in southeastern Spain: a study of attitude toward organ donation.
AB  - BACKGROUND: Spain is frequently a place of residence for a high percentage of the
      German population. Our aim is to analyze the attitude of the German population
      that is resident in Spain toward organ donation. METHODS: A sample of German
      residents in the south east of Spain was obtained randomly between November 2005
      and April 2006 (n = 227). Attitude was evaluated using a validated questionnaire.
      This survey was self-administered and completed anonymously. CONTROL GROUP: a
      sample of 2000 Spanish citizens. RESULTS: There is a favorable attitude toward
      donation in 64% of respondents, similar to the control group (64% vs. 63%; p =
      0.8545). The most important factors that affect such attitude are: (i) having
      dependents (odds ratio = 4.569); (ii) having talked about donation within the
      family (OR = 4.132); (iii) being willing to accept an autopsy if one were
      necessary (OR = 5.952); (iv) having had previous experience of organ donation and
      transplantation (OR = 5.814); (v) not being concerned about mutilation of the
      cadaver (OR = 8.792); and (vi) the attitude of one's partner toward donation,
      especially when this is negative (OR = 0.002). CONCLUSIONS: The attitude toward
      organ donation of Germans who usually reside in Spain is the same as that
      described in the native Spanish population, and is determined by many
      psychosocial factors.

PMID- 19744092
TI  - Challenges in diagnosing acute pancreatitis in renal transplant patients.
AB  - Acute pancreatitis is a recognized occurrence in patients with end-stage renal
      disease, those on dialysis and those who have undergone renal transplantation.
      The incidence is significantly increased in comparison to the general population
      and carries significant mortality. We report two cases of acute pancreatitis that
      occurred in stable renal transplant recipients, and in which there was diagnostic
      difficulty. The etiology of the acute pancreatitis is not always identifiable in
      these patients. Classical symptoms and laboratory findings are often absent,
      which may cause diagnostic difficulty. Our experience suggests that in
      immunosuppressed patients with unexplained abdominal pain or abnormal liver
      function tests, acute pancreatitis should be considered at an early stage in
      order to initiate appropriate treatment and therefore minimize mortality and
      morbidity.

PMID- 19744093
TI  - Impact of RIFLE classification in liver transplantation.
AB  - Acute renal failure (ARF) is common after orthotopic liver transplantation (OLT).
      The aim of this study was to evaluate the prognostic value of RIFLE
      classification in the development of CKD, hemodialysis requirement, and
      mortality. Patients were categorized as risk (R), injury (I) or failure (F)
      according to renal function at day 1, 7 and 21. Final renal function was
      classified according to K/DIGO guidelines. We studied 708 OLT recipients,
      transplanted between September 1992 and March 2007; mean age 44 +/- 12.6 yr, mean
      follow-up 3.6 yr (28.8% > or = 5 yr). Renal dysfunction before OLT was known in
      21.6%. According to the RIFLE classification, ARF occurred in 33.2%: 16.8% were R
      class, 8.5% I class and 7.9% F class. CKD developed in 45.6%, with stages 4 or 5d
      in 11.3%. Mortality for R, I and F classes were, respectively, 10.9%, 13.3% and
      39.3%. Severity of ARF correlated with development of CKD: stage 3 was associated
      with all classes of ARF, stages 4 and 5d only with severe ARF. Hemodialysis
      requirement (23%) and mortality were only correlated with the most severe form of
      ARF (F class). In conclusion, RIFLE classification is a useful tool to stratify
      the severity of early ARF providing a prognostic indicator for the risk of CKD
      occurrence and death.

PMID- 19744094
TI  - Two-year follow-up of a prospective study of circulating regulatory T cells in
      renal transplant patients.
AB  - CD4(+)CD25(high)FOXP3(+) regulatory T cells (Tregs) are involved in
      alloreactivity and may be associated with protection from rejection. Their
      quantification in peripheral blood could guide clinicians in the management of
      renal transplant patients. Thus, we prospectively monitored the levels and in
      vitro suppression of circulating Tregs in 33 renal transplant patients from
      deceased donors within the first two yr of transplantation. Patients received
      maintenance immunosuppression with tacrolimus, mofetil mycophenolate and
      prednisolone. Results showed that peripheral blood Tregs were significantly lower
      six months after transplantation and recovered to almost basal levels at first
      post-transplant year. The number of circulating Tregs increased significantly
      over basal levels afterwards. The decrease in circulating Tregs at six months may
      be explained by the high load of tacrolimus, as demonstrated by the inverse
      correlation between the blood concentration of Tregs and tacrolimus. Likewise,
      nine patients treated with anti-CD25 antibodies showed higher numbers of Tregs at
      six months than those that did not, although differences were not observed later.
      In conclusion, circulating Tregs decrease in the first six months but recover
      thereafter up to two yr after kidney transplantation. Such a decrease is favored
      by high levels of tacrolimus but not by induction protocols with anti-CD25.

PMID- 19744095
TI  - Extracorporeal membrane oxygenation bridge to adult heart transplantation.
AB  - Extracorporeal membrane oxygenation (ECMO) can rescue some critical patients with
      circulatory collapse when intra-aortic balloon pump (IABP) and ventricular assist
      devices (VAD) are not suitable. A subset of these patients can use ECMO for
      direct bridging, or indirect double bridging via VAD to heart transplantation
      (HTx). For these patients, we identified risk factors for unsuccessful ECMO
      bridging, with survival to receiving either HTx or VAD as the measure of success.
      The characteristics evaluated were age, sex, body mass index, pre-ECMO
      cardiopulmonary resuscitation (CPR), IABP use, dialysis use, sequential organ
      failure assessment (SOFA) score, and the etiology of cardiomyopathy. From January
      1995 to August 2007, there were 70 adult ECMO patients with the intent to bridge
      to HTx (male: 55, age: 46 +/- 14 yr). Thirty-one patients (44%) were successful
      in bridging. A stepwise multivariate logistic regression analysis found that age
      > 50 yr (p = 0.003), pre-ECMO CPR (p = 0.001) and SOFA score > 10 at ECMO
      initiation (p = 0.018) were significant independent predictors of unsuccessful
      bridging. Direct VAD implantation, if possible, is preferable to double bridging
      in patients over 50 yr. Also, elective ECMO support before hemodynamic
      deterioration to cardiac arrest or multiple organ dysfunction would improve rates
      of successful ECMO bridging.

PMID- 19744096
TI  - Persistent fatigue in liver transplant recipients: a two-year follow-up study.
AB  - BACKGROUND: Fatigue after liver transplantation (LTx) is a major problem that is
      associated with lower daily functioning and health-related quality of life
      (HRQoL). This study aimed to assess changes over time in fatigue following LTx.
      We also examined daily functioning and HRQoL changes over time and assessed the
      influence of fatigue and changes in fatigue on daily functioning and HRQoL. We
      determined whether sleep quality, anxiety, and depression were associated with
      fatigue. METHODS: We identified 70 LTx recipients who had previously participated
      in a cross-sectional study and reassessed them after two yr to determine changes
      in level of fatigue, daily functioning, and HRQoL. We also assessed sleep
      quality, anxiety, and depression after two yr. RESULTS: Level of fatigue and
      level of daily functioning were unchanged at follow-up. HRQoL domains remained
      stable or worsened. Fatigue was a significant predictor of daily functioning and
      all HRQoL domains (p < 0.01). Change in fatigue was a significant predictor of
      daily functioning and the HRQoL domains of "physical functioning,""vitality," and
      "pain" (p < 0.05). Sleep quality, anxiety, and depression were associated with
      fatigue severity (r = 0.35 to r = 0.60, p < 0.05). CONCLUSION: This longitudinal
      study shows that fatigue is a chronic problem after LTx and that daily
      functioning and HRQoL do not improve over time. This study supports the need for
      intervention programs to address fatigue after LTx.

PMID- 19744105
TI  - Kisspeptin serum levels in girls with central precocious puberty: a long way to
      go.

PMID- 19744106
TI  - How should we treat patients with low serum thyrotropin concentrations?
AB  - Subclinical hyperthyroidism (SH) is defined by a low serum thyrotropin (TSH)
      concentration in the presence of normal levels of free thyroxine (FT4) and free
      triiodothyronine (FT3). However, it is helpful to distinguish between those with
      a detectable but low TSH value (in the 0.1-0.4 mU/l range) and those with a fully
      suppressed TSH (<0.1 mU/l), and we suggest the designation of grade I and grade
      II SH, respectively. Together, these patterns of thyroid function tests are found
      in 1-3% of the elderly population, and are associated with significant morbidity
      and mortality in longitudinal epidemiological surveys. There are a number of
      causes for this picture, which include endogenous thyroid disease, drug effects
      and concomitant nonthyroidal illness. Treatments commonly employed in the
      management of thyrotoxicosis are effective at correcting the biochemical
      abnormalities of SH but have not been shown to improve clinical outcome or
      symptoms. There is little good quality evidence available to guide the assessment
      or management of these patients. This review summarizes the clinical significance
      of SH and aims to provide guidance about whether we should treat patients with
      low serum TSH concentrations.

PMID- 19744107
TI  - Recurrence detection in differentiated thyroid cancer patients with elevated
      serum level of antithyroglobulin antibody: special emphasis on using (18)F-FDG
      PET/CT.
AB  - OBJECTIVE: A clinical challenge is presented by differentiated thyroid cancer
      (DTC) patients who show increased serum antithyroglobulin antibody (TgAb) level
      with undetectable thyroglobulin (Tg) and negative radioiodine whole body scan (I
      WBS). The aim of this study is to investigate the recurrence in DTC patients with
      elevated TgAb by using (18)F-FDG PET/CT (PET/CT) in addition to I-WBS and neck
      ultrasonography (USG). SUBJECTS AND DESIGN: A total of 276 TgAb+ patients were
      enrolled. Recurrence was assessed and compared between TgAb+ and TgAb- patients.
      TgAb+ patients were further categorized into two groups of 35-140 U/ml (Group A)
      and 140 U/ml or greater (Group B), according to receiver operating characteristic
      (ROC) curve analysis. Tumoural status was evaluated regarding the TgAb positivity
      and the degree of increase of TgAb. RESULTS: Thirty-seven (13.4%) of 276 TgAb+
      patients were finally diagnosed with recurrence, compared with 21 (13.5%) of 156
      TgAb- patients (P = 0.987). There was a correlation between TgAb level and
      recurrence (P = 0.032). Recurrence was more common in Group B than Group A (27.8%
      and 9.9%, respectively, P = 0.001). Recurrence was found in 37.5% of 24 TgAb+/Tg-
      patients who showed a gradually increasing tendency in serial measurements of
      TgAb. Sixteen cervical foci (21.1%) missed on neck USG and 17 lesions (22.4%)
      located outside the neck were additionally detected with PET/CT in TgAb+
      patients. CONCLUSIONS: TgAb plays a complementary role to Tg in the detection of
      recurrence of DTC. Tumour recurrence was more frequent in patients with elevated
      TgAb level over 140 U/ml or a trend toward increasing levels. PET/CT could
      provide additional information to I-WBS and neck USG in detecting tumour
      recurrence in patients with elevated TgAb.

PMID- 19744108
TI  - Association between sex steroids and cognition in elderly men.
AB  - OBJECTIVE: To examine the association of cognitive function with sex steroid and
      sex hormone binding globulin (SHBG) levels among elderly men. DESIGN: Prospective
      cohort study, The Osteoporotic Fractures in Men Study (MrOS), consisting of 5995
      US community dwelling men of 65 years or older. PATIENTS: One thousand six
      hundred and two men were chosen randomly from MrOS cohort for sex steroid level
      measurements by Mass Spectrometry (MS) at baseline. Two thousand six hundred and
      twenty-three MrOS participants with sex steroids measured using RIA were also
      examined. MEASUREMENTS: Baseline and follow-up (4.5 years later) performance on
      two cognitive tests: Trails B (executive function and motor speed) and 3MS
      (global cognitive function). Baseline total testosterone and oestradiol were
      measured by MS. Free testosterone (free-T) and free oestradiol (free-E) were
      calculated. SHBG was measured by radioimmunoassay. Data were analysed using
      linear regression. RESULTS: Baseline free-T and free-E levels were not associated
      with cognitive performance or change in cognition, following adjustment for age,
      education, race, health status and alcohol use. Baseline SHBG levels were
      inversely associated with follow-up trails B (P = 0.03) and 3MS performance (P =
      0.02). Higher SHBG was associated with an increased risk of cognitive decline.
      Total sex steroid levels were not associated with cognitive performance.
      CONCLUSIONS: Despite large numbers of participants and rigorous sex steroid
      measurements, we did not observe an association between cognition and either
      testosterone or oestradiol levels. We conclude that endogenous sex steroids in
      the normal range are not related to executive function or global cognitive
      function in elderly men. High SHBG deserves further examination as a risk factor
      for cognitive decline.

PMID- 19744109
TI  - Revisiting infant growth prior to childhood onset type 1 diabetes.
AB  - OBJECTIVE: Accelerated early growth prior to childhood type 1 diabetes onset is
      associated with an increased risk for type 1 diabetes (T1D). We aimed to study
      early growth, correcting for the previously neglected confounder of familial
      effects. DESIGN: Infant growth was studied in a retrospective family case-control
      study of diabetic children in which siblings acted as matched familial controls
      allowing correction for confounders related to family particulars. PATIENTS:
      Weight and height data were collected from 213 juvenile onset type 1 diabetic
      children and their 255 healthy siblings. Growth in the first 4 years of life was
      studied using repeated measurement. The degree of early overgrowth was correlated
      with age of clinical onset. RESULTS: Birth weight and length did not differ
      between later diabetic children and their siblings. In the first year of life,
      weight standard deviation score (SDS) differed between patients and sibs (P =
      0.0001). After the first year, both diabetic children and sibs showed parallel
      enhanced weight and height gain SDS until age 4 years. Earlier onset diabetes was
      associated with a higher weight SDS at 6 months of age. CONCLUSION: In this
      family case-control study the association of increased growth with development of
      T1D is limited to the first year of life implying that increased growth beyond
      the first year can be attributed to familial growth patterns, rather than
      predisposition to T1D per se. Age at disease onset correlated with increased
      weight in the first 6 months of life, indicating importance of features very
      early in life on later development of T1D.

PMID- 19744110
TI  - Norcantharidin induces HT-29 colon cancer cell apoptosis through the alphavbeta6
      extracellular signal-related kinase signaling pathway.
AB  - Norcantharidin has been used as an efficacious anticancer drug in China for many
      years, but its true mechanism remains poorly understood. Intriguingly, in an in
      vitro series study of anticancer drugs, we found that norcantharidin can
      effectively inhibit epithelial tumor cells from expressing integrin alphavbeta6.
      Our previous studies have confirmed that integrin alphavbeta6 is closely relevant
      to malignant epithelial cell tumor biology behavior, and it can promote cancer
      cells to invade and metastasize through a special alphavbeta6-extracellular
      signal-related kinase (ERK) direct signaling pathway. In this study, we
      investigated the relationship between the norcantharidin anticancer mechanism and
      integrin alphavbeta6. After HT-29 colon cancer cells were treated with
      norcantharidin, cell apoptosis increased remarkably. The expression of
      alphavbeta6 and the amount of p-ERK decreased substantially; simultaneously, the
      linkage between alphavbeta6 and ERK was barely detectable. However, the
      expression of other integrins and the levels of mitogen-activated protein kinase
      hardly changed. On these grounds, we presumed that norcantharidin induced HT-29
      colon cancer cell apoptosis through the alphavbeta6-ERK signaling pathway. This
      finding elicited a novel strategy for targeting the whole alphavbeta6-ERK signal
      pathway, rather than simply blocking the combining site of alphavbeta6-ERK in
      colon cancer treatment.

PMID- 19744111
TI  - Topiramate concentrations in neonates treated with prolonged whole body
      hypothermia for hypoxic ischemic encephalopathy.
AB  - PURPOSE: Therapeutic hypothermia reduces mortality and neurologic impairment in
      neonates with hypoxic-ischemic encephalopathy. Topiramate exerts a
      neuroprotective effect in asphyxiated neonatal animal models. However, no studies
      have investigated the association of hypothermia and topiramate, because
      topiramate pharmacokinetics during hypothermia and the optimal administration
      schedule are unknown. The influence of hypothermia on topiramate pharmacokinetics
      was evaluated in asphyxiated neonates treated with prolonged whole-body
      hypothermia and topiramate. METHODS: Thirteen term newborns were treated with
      mild or deep whole body hypothermia for 72 h; all received oral topiramate, 5
      mg/kg once a day for the first 3 days of life, and seven had concomitant
      phenobarbital treatment. Topiramate concentrations were measured on serial dried
      blood spots. RESULTS: Topiramate concentrations were within the reference range
      in 11 of 13 newborns, whereas concentrations exceeded the upper limit in 2 of 13,
      both newborns on deep hypothermia. Topiramate concentrations reached a virtual
      steady state in nine newborns, for whom pharmacokinetic parameters were
      calculated. Values of topiramate maximal and minimal concentration, half-life,
      average concentration, and area under the time-concentration curve resulted in
      considerably higher values than those reported in normothermic infants. With
      respect to normothermic infants, time of maximal concentration was mildly delayed
      and apparent total body clearance was lower, suggesting slower absorption and
      elimination. Pharmacokinetic parameters did not differ significantly between
      infants on deep versus mild hypothermia and in those on topiramate monotherapy
      versus add-on phenobarbital. CONCLUSION: Most neonates on prolonged hypothermia
      treated with topiramate 5 mg/kg once a day exhibited drug concentrations within
      the reference range for the entire treatment duration.

PMID- 19744112
TI  - Antiepileptic drugs in children in developing countries: research and treatment
      guideline needs.
AB  - Epilepsy is the most common neurologic disorder in childhood. Effective
      interventions are available for treatment; however, the treatment gap in children
      is more than 80% in many developing countries. An important reason for this huge
      treatment gap is limited access to antiepileptic drugs (AEDs). This article
      discusses the reasons for such a treatment gap, and possible ways forward in
      improving care of children with epilepsy worldwide.

PMID- 19744113
TI  - Extent of initial injury determines language lateralization in mesial temporal
      lobe epilepsy with hippocampal sclerosis (MTLE-HS).
AB  - PURPOSE: To assess the prevalence and attributes of atypical language
      lateralization (ALL) in patients with left mesial temporal lobe epilepsy
      associated with hippocampal sclerosis (MTLE-HS). METHODS: We recruited
      consecutive patients with left MTLE-HS, who had undergone resective surgery and
      had pathologically proven HS. Based on the Wada test, language lateralization was
      classified into typical (left hemispheric) or atypical (right hemispheric or
      codominant). We assessed the attributes of patients with ALL using univariate and
      multivariate analyses. RESULTS: Of 124 patients with left MTLE-HS, 23 (18.5%) had
      ALL. ALL occurred more frequently in patients with severe initial precipitating
      injury (IPI), early onset of epilepsy, and a short latent period between IPI and
      onset of habitual seizures. ALL was more common in patients with bitemporal and
      extratemporal interictal epileptiform discharges (IEDs) on electroencephalogram
      (EEG) and extratemporal changes on magnetic resonance imaging (MRI). On
      multivariate analyses, the age at onset of habitual seizures <6 years, atypical
      IPI, nonunilateral temporal IEDs, and extratemporal MRI abnormalities
      independently predicted ALL. The likelihood of ALL was very low ( approximately
      1%) when all of these four risk factors were absent, whereas it was very high
      (>95%), if any three or all four of them were present. CONCLUSIONS: ALL occurs in
      one-fifth of patients with left MTLE-HS. ALL is more frequent in those with
      structural or functional extrahippocampal involvement and early onset of epilepsy
      interrupting the development of normal language networks. Because ALL is uncommon
      in those with damage/dysfunction restricted to the hippocampus, the hippocampus
      itself may have only a limited role in determining language lateralization.

PMID- 19744114
TI  - Placebo-corrected efficacy of modern antiepileptic drugs for refractory epilepsy:
      systematic review and meta-analysis.
AB  - Although adjunctive treatment with modern antiepileptic drugs (AEDs) is standard
      care in refractory epilepsy, it is unclear how much of the effect can be
      attributed directly to the AEDs and how much to the beneficial changes seen with
      placebo. Therefore, we performed a systematic review and meta-analysis of the
      evidence to determine the placebo-corrected net efficacy of adjunctive treatment
      with modern AEDs on the market for refractory epilepsy. Of 317 potentially
      eligible articles reviewed in full text, 124 (39%) fulfilled eligibility
      criteria. After excluding 69 publications, 55 publications of 54 studies in
      11,106 adults and children with refractory epilepsy form the basis of evidence.
      The overall weighted pooled-risk difference in favor of AEDs over placebo for
      seizure-freedom in the total sample of adults and children was 6% [95% confidence
      interval (CI) 4-8, z = 6.47, p < 0.001] and 21% (95% CI 19-24, z = 17.13, p <
      0.001) for 50% seizure reduction. Although the presence of moderate heterogeneity
      may reduce the validity of the results and limit generalizations from the
      findings, we conclude that the placebo-corrected efficacy of adjunctive treatment
      with modern AEDs is disappointingly small and suggest that better strategies of
      finding drugs are needed for refractory epilepsy, which is a major public health
      problem.

PMID- 19744115
TI  - The treatment gap of epilepsy in a rural district of Vietnam: a study from the
      EPIBAVI project.
AB  - We analyzed the treatment gap by interviewing 189 persons previously identified
      as having active epilepsy in a population-based epidemiological project in a
      rural district of Vietnam (EPIBAVI). Only 29 persons were on regular treatment
      with antiepileptic drugs (AEDs) at the time of the survey; treatment gap 84.7%
      [95% confidence interval (CI) 79.5-89.8%). The treatment gap was not associated
      with age, gender, education, income, or seizure control status, but was higher
      among those living single compared to those who were married (p < 0.05). The most
      common reason for not taking AEDs expressed by patients who never tried, as well
      as among those who tried but discontinued, AEDs was the perception that their
      seizures were too few to justify the trouble and costs associated with treatment.

PMID- 19744116
TI  - Nonconvulsive status epilepticus and coma.
AB  - Nonconvulsive status epilepticus (NCSE) in a comatose patient cannot be diagnosed
      without electroencephalography (EEG). In many advanced coma stages, the EEG
      exhibits continuous or periodic EEG abnormalities, but their causal role in coma
      remains unclear in many cases. To date there is no consensus on whether to treat
      NCSE in a comatose patient in order to improve the outcome or to retract from
      treatment, as these EEG patterns might reflect the end stages of a dying brain.
      On the basis of EEG, NCSE in comatose patients may be classified as generalized
      or lateralized. This review aims to summarize the ongoing debate of NCSE and coma
      and to critically reassess the available literature on coma with epileptiform EEG
      pattern and its prognostic and therapeutic implications. The authors suggest
      distinguishing NCSE proper and comatose NCSE, which includes coma with continuous
      lateralized discharges or generalized epileptiform discharges (coma-LED, coma
      GED). Although NCSE proper is accompanied by clinical symptoms suggestive of
      status epilepticus and mild impairment of consciousness, such as in absence
      status or complex focal status epilepticus, coma-LED and coma-GED represent deep
      coma of various etiology without any clinical motor signs of status epilepticus
      but with characteristic epileptiform EEG pattern. Hence coma-LED and coma-GED can
      be diagnosed with EEG only. Subtle or stuporous status epilepticus and epilepsia
      partialis continua-like symptoms in severe acute central nervous system (CNS)
      disorders represent the borderland in this biologic continuum between NCSE proper
      and comatose NCSE (coma-LED/GED). This pragmatic differentiation could act as a
      starting point to solve terminologic and factual confusion.

PMID- 19744117
TI  - Sex reversal: a fountain of youth for sex chromosomes?
AB  - Nonrecombining Y chromosomes are expected to degenerate through the progressive
      accumulation of deleterious mutations. In lower vertebrates, however, most
      species display homomorphic sex chromosomes. To address this, paradox I propose a
      role for sex reversal, which occasionally occurs in ectotherms due to the general
      dependence of physiological processes on temperature. Because sex-specific
      recombination patterns depend on phenotypic, rather than genotypic sex,
      homomorphic X and Y chromosomes are expected to recombine in sex-reversed
      females. These rare events should generate bursts of new Y haplotypes, which will
      be quickly sorted out by natural or sexual selection. By counteracting Muller's
      ratchet, this regular purge should prevent the evolutionary decay of Y
      chromosomes. I review empirical data supporting this suggestion, and propose
      further investigations for testing it.

PMID- 19744118
TI  - Latitudinal variation in speciation mechanisms in frogs.
AB  - Speciation often has a strong geographical and environmental component, but the
      ecological factors that potentially underlie allopatric and parapatric speciation
      remain understudied. Two ecological mechanisms by which speciation may occur on
      geographic scales are allopatric speciation through niche conservatism and
      parapatric or allopatric speciation through niche divergence. A previous study on
      salamanders found a strong latitudinal pattern in the prevalence of these
      mechanisms, with niche conservatism dominating in temperate regions and niche
      divergence dominating in the tropics, and related this pattern to Janzen's
      hypothesis of greater climatic zonation between different elevations in the
      tropics. Here, we test for latitudinal patterns in speciation in a related but
      more diverse group of amphibians, the anurans. Using data from up to 79 sister
      species pairs, we test for latitudinal variation in elevational and climatic
      overlap between sister species, and evaluate the frequency of speciation via
      niche conservatism versus niche divergence in relation to latitude. In contrast
      to salamanders, we find no tendency for greater niche divergence in the tropics
      or for greater niche conservatism in temperate regions. Although our results
      support the idea of greater climatic zonation in tropical regions, they show that
      this climatic pattern does not lead to straightforward relationships between
      speciation, latitude, and niche evolution.

PMID- 19744119
TI  - Clinal patterns of chromosomal inversion polymorphisms in Drosophila subobscura
      are partly associated with thermal preferences and heat stress resistance.
AB  - Latitudinal clines in the frequency of various chromosomal inversions are well
      documented in Drosophila subobscura. Because these clines are roughly parallel on
      three continents, they have undoubtedly evolved by natural selection. Here, we
      address whether individuals carrying different chromosomal arrangements also vary
      in their thermal preferences (T(p)) and heat stress tolerance (T(ko)). Our
      results show that although T(p) and T(ko) were uncorrelated, flies carrying "cold
      adapted" gene arrangements tended to choose lower temperatures in the laboratory
      or had a lower heat stress tolerance, in line with what could be expected from
      the natural patterns. Different chromosomes were mainly responsible for the
      underlying genetic variation in both traits, which explains why they are linearly
      independent. Assuming T(p) corresponds closely with temperatures that maximize
      fitness our results are consistent with previous laboratory natural selection
      experiments showing that thermal optimum diverged among thermal lines, and that
      chromosomes correlated with T(p) differences responded to selection as predicted
      here. Also consistent with data from the regular tracking of the inversion
      polymorphism since the colonization of the Americas by D. subobscura, we
      tentatively conclude that selection on tolerance to thermal extremes is more
      important in the evolution and dynamics of clinal patterns than the relatively
      "minor" adjustments from behavioral thermoregulation.

PMID- 19744120
TI  - Species hybrids in the laboratory but not in nature: a reanalysis of premating
      isolation between Drosophila arizonae and D. mojavensis.
AB  - Understanding speciation relies critically on the identification of mechanisms
      responsible for maintaining species integrity (i.e., reproductive isolation)
      especially when closely related species are sympatric in nature. Studies of
      reproductive isolation in Drosophila often involve laboratory mating experiments
      that assume that patterns of mate choice in the laboratory are similar to those
      in the wild. Two sibling species, Drosophila arizonae and D. mojavensis, known to
      exhibit low levels of interspecific hybridization in the laboratory, but not in
      nature, were used in multiple-choice mating trials using various mating chamber
      designs as well as synthetic and natural media for developing larvae and courting
      adults. Sympatric populations were more sexually isolated than allopatric ones,
      consistent with past studies, and all experimental variables tested (chamber
      size, host plant presence and rearing substrates) had significant effects on
      levels of premating isolation between these species. Flies reared on cactus
      showed increased premating isolation versus those reared on synthetic laboratory
      food as did providing fermenting host plant tissue during mating trials. Also,
      surprisingly, smaller mating chambers led to an increase in premating isolation
      versus larger containers. The design of these types of mating trials is thus
      critical to understanding how mating behaviors in the laboratory are related to
      those in natural populations.

PMID- 19744121
TI  - Evolution of identity signals: frequency-dependent benefits of distinctive
      phenotypes used for individual recognition.
AB  - Identifying broad-scale evolutionary processes that maintain phenotypic
      polymorphisms has been a major goal of modern evolutionary biology. There are
      numerous mechanisms, such as negative frequency-dependent selection, that may
      maintain polymorphisms, although it is unknown which mechanisms are prominent in
      nature. Traits used for individual recognition are strikingly variable and have
      evolved independently in numerous lineages, providing an excellent model to
      investigate which factors maintain ecologically relevant phenotypic
      polymorphisms. Theoretical models suggest that individuals may benefit by
      advertising their identities with distinctive, recognizable phenotypes. Here, we
      test the benefits of advertising one's identity with a distinctive phenotype. We
      manipulated the appearance of Polistes fuscatus paper wasp groups so that three
      individuals had the same appearance and one individual had a unique, easily
      recognizable appearance. We found that individuals with distinctive appearances
      received less aggression than individuals with nondistinctive appearances.
      Therefore, individuals benefit by advertising their identity with a unique
      phenotype. Our results provide a potential mechanism through which negative
      frequency-dependent selection may maintain the polymorphic identity signals in P.
      fuscatus. Given that recognition is important for many social interactions,
      selection for distinctive identity signals may be an underappreciated and
      widespread mechanism underlying the evolution of phenotypic polymorphisms in
      social taxa.

PMID- 19744122
TI  - A test for Cope's rule.
AB  - Cope's Rule refers to the tendency of body size to increase along an evolutionary
      lineage. This rule is commonly tested by comparing size differences in pairs of
      taxa, one of which is assumed to be ancestral to the other. It has recently been
      pointed out that this approach fails to account for the unknown number of
      speciation events separating each pair. Here, a test that does account for this
      degree of separation is described and applied to some published data for
      dinosaurs. A by-product of the analysis is an estimate of the origination rate of
      dinosaur species.

PMID- 19744123
TI  - Rapid sympatry explains greater color pattern divergence in high latitude birds.
AB  - Latitudinal variation in patterns of evolution has fascinated biologists for over
      a century, but our understanding of latitudinal differences in evolutionary
      processes-such as selection and drift-remains limited. Here, we test for, and
      find, accelerated evolution of color patterns in bird taxa that breed at higher
      latitudes compared with those breeding in the tropics, analyzing data from seven
      diverse avian families. Most important, we show that the extent of overlap of
      species' breeding ranges (degree of sympatry) explains the elevated rate of color
      pattern evolution at higher latitudes. We suggest that the dynamic shifts in
      breeding ranges that accompanied climatic changes during the last 3 million years
      (Milankovitch Oscillations) resulted in more rapid and more frequent secondary
      contact at high latitudes. We argue that sympatry among diverging clades causes
      greater divergence of color traits in birds at higher latitudes through sexual,
      social, or ecological character displacement that accelerate rates of evolution,
      and through the selective elimination of weakly differentiated lineages that
      hybridize and fuse in sympatry (differential fusion).

PMID- 19744124
TI  - Adaptionism-30 years after Gould and Lewontin.
AB  - Gould and Lewontin's 30-year-old critique of adaptionism fundamentally changed
      the discourse of evolutionary biology. However, with the influx of new ideas and
      scientific traditions from genomics into evolutionary biology, the old
      adaptionist controversies are being recycled in a new context. The insight gained
      by evolutionary biologists, that functional differences cannot be equated to
      adaptive changes, has at times not been appreciated by the genomics community. In
      this comment, I argue that even in the presence of both functional data and
      evidence for selection from DNA sequence data, it is still difficult to construct
      strong arguments in favor of adaptation. However, despite the difficulties in
      establishing scientific arguments in favor of specific historic evolutionary
      events, there is still much to learn about evolution from genomic data.

PMID- 19744125
TI  - PCR- and restriction endonuclease-based detection of IDH1 mutations.
AB  - Hotspot mutations in codon 132 of the gene encoding isocitrate dehydrogenase 1
      (IDH1) have emerged as the most frequent DNA alteration in astrocytomas,
      oligodendrogliomas and oligoastrocytomas. These mutations have been shown to be
      of significant diagnostic and prognostic value. So far, assessment of IDH1
      mutation relied on DNA sequencing techniques. We generated a set of primers
      suitable for endonuclease-based detection of hotspot mutations in codon 132 of
      IDH1. This primer set will allow determining these mutations without the need of
      DNA sequencing. One set of primer sets is designed to detect the presence or
      absence of IDH1 mutations in codon 132, while the other primer sets individually
      recognize the R132H, R132C, R132S, R132G and R132L mutations.

PMID- 19744126
TI  - Hyperhemolysis syndrome in a patient with sickle cell disease with
      erythrophagocytosis in peripheral blood.

PMID- 19744127
TI  - Chronic myeloid leukemia and BCR/ABL signal pathways are not associated with AKT1
      pleckstrin homology domain (E17K) mutations.

PMID- 19744128
TI  - Elevated serum parathormone levels are associated with myocardial iron overload
      in patients with beta-thalassaemia major.
AB  - OBJECTIVES: Despite advances in conventional treatment, iron-induced
      cardiomyopathy is still the most frequent cause of death among patients with beta
      thalassaemia major. Recent studies have correlated increased myocardial iron
      content to decreased levels of vitamin D in thalassaemic patients. The aim of
      this study was to measure parathormone (PTH) and metabolites of vitamin D and
      consequently to investigate whether these parameters predispose to myocardial
      iron overload in patients with beta-thalassaemia major. METHODS: In 62 patients
      (29 M and 33 F, mean age: 22.79 +/- 6.18 yr) with beta-thalassaemia major levels
      of intact parathormone (iPTH) and vitamin D metabolites [25(OmicronH)D(3) and
      1,25(OmicronH)(2)D(3)] were measured in serum. Additionally, estimation of
      myocardial iron content was performed by magnetic resonance imaging, whereas mean
      serum ferritin concentrations were calculated for 1 yr prior to the study.
      RESULTS: Results showed markedly decreased levels of serum 25(OH)D(3) in 37
      patients (60%), whereas 7 patients (11%) had borderline 25(OH)D(3) levels
      (between 50 and 75 nmol/L). Serum iPTH levels were significantly higher in
      patients having increased myocardial iron compared to those having normal
      myocardial iron (44.04 +/- 22.09 pg/mL vs. 31.39 +/- 14.30 pg/mL, P = 0.017).
      Multivariant regression analysis identified PTH levels as the major predictor of
      increased myocardial iron.

PMID- 19744129
TI  - The role of microRNAs in normal and malignant hematopoiesis.
AB  - MicroRNAs are small non-coding RNAs that act at the post-transcriptional level,
      regulating protein expression by repressing translation or destabilizing mRNA
      target. Because of their discovery, microRNAs have been associated with almost
      every normal cell function, including proliferation, differentiation and
      apoptosis. Several lines of evidence suggest that they have an important role in
      normal hematopoiesis as exemplified by the role of mir-155 and mir-150 in the
      differentiation of B and T lymphocytes, the suppressive role of mir-221 and mir
      222 in erythroid differentiation, the inhibitory effect of mir-181 on
      hematopoietic differentiation and the induction of myeloid differentiation by mir
      223. Moreover, they play a role both as oncogenes, probably by a variety of
      mechanisms, namely through elimination of tumor suppressor proteins, or as tumor
      suppressor genes by targeting oncogenic mRNAs. Their aberrant expression has been
      associated with solid tumors and hematopoietic malignancies as suggested by the
      frequent deletion of mir-15a and mir-16-1 in chronic lymphocytic leukemia, the
      increased levels of mir-155 in diffuse large B-cell lymphomas and the increased
      levels of mir-181 in acute myeloid leukemia M1 and M2. The purpose of this review
      is to summarize current knowledge on the role of microRNAs in normal
      hematopoiesis and hematopoietic malignancies and, moreover, to highlight their
      role as potential therapeutic tools.

PMID- 19744130
TI  - Evidence for a novel mechanism for gene amplification in multiple myeloma: 1q12
      pericentromeric heterochromatin mediates breakage-fusion-bridge cycles of a 1q12
      approximately 23 amplicon.
AB  - Gene amplification is defined as a copy number (CN) increase in a restricted
      region of a chromosome arm, and is a mechanism for acquired drug resistance and
      oncogene activation. In multiple myeloma (MM), high CNs of genes in a 1q12
      approximately 23 amplicon have been associated with disease progression and poor
      prognosis. To investigate the mechanisms for gene amplification in this region in
      MM, we performed a comprehensive metaphase analysis combining G-banding,
      fluorescence in situ hybridization, and spectral karyotyping in 67 patients with
      gain of 1q. In six patients (9%), evidence for at least one breakage-fusion
      bridge (BFB) cycle was found. In three patients (4%), extended ladders of 1q12
      approximately 23 amplicons were identified. Several key structures that are
      predicted intermediates in BFB cycles were observed, including: equal-spaced
      organization of amplicons, inverted repeat organization of amplicons along the
      same chromosome arm, and deletion of sequences distal to the amplified region.
      The 1q12 pericentromeric heterochromatin region served as both a recurrent
      breakpoint as well as a fusion point for sister chromatids, and ultimately
      bracketed both the proximal and distal boundaries of the amplicon. Our findings
      provide evidence for a novel BFB mechanism involving 1q12 pericentromeric
      breakage in the amplification of a large number of genes within a 1q12
      approximately 23 amplicon.

PMID- 19744131
TI  - A phase I/II study of the safety and efficacy of the addition of sirolimus to
      tacrolimus/methotrexate graft versus host disease prophylaxis after allogeneic
      haematopoietic cell transplantation in paediatric acute lymphoblastic leukaemia
      (ALL).
AB  - Sirolimus has been shown to have activity against human acute lymphoblastic
      leukaemia at serum levels used for immunosuppression. We hypothesized that the
      addition of sirolimus to a tacrolimus/methotrexate graft-versus-host disease
      (GVHD) prophylaxis regimen would decrease relapse after haematopoietic stem cell
      transplantation and initiated a phase I/II study to demonstrate safety,
      feasibility, and efficacy. The study cohort included 18 patients in high-risk
      (HR) first complete remission (CR1), 16 in HR CR2, 17 in intermediate risk (IR)
      CR2, and 12 in CR3+. The 2-year event-free survival (EFS) of the cohort was 66%
      (standard error 6.4). EFS of risk groups was 74%, 81%, 44% and 46% for CR1, IR
      CR2, HR CR2 and CR3+ patients respectively, and did not differ by stem cell
      source. Cumulative incidence of acute GVHD grade II-IV and III-IV was 38% and 21%
      respectively, while the cumulative incidence of chronic GVHD was 32%. Cumulative
      incidence of transplant-related mortality and relapse was 10% and 25%
      respectively. Significant toxicities included veno-occlusive disease [seven
      patients (11%)], transplant-associated microangiopathy (three patients), and
      idiopathic pneumonitis (one patient). In summary, sirolimus-based GVHD
      prophylaxis can be given safely in this population and early survival results are
      promising. A phase III trial to test whether sirolimus decreases relapse and
      improves outcome after transplantation for ALL is ongoing.

PMID- 19744132
TI  - Inflammatory cell types in nasal polyps.

PMID- 19744134
TI  - Reactivity to images in health and irritable bowel syndrome.
AB  - BACKGROUND: We have been using a medical artist to record and paint the images
      patients have of their irritable bowel syndrome (IBS) and have hypothesized that
      the reaction to such images might differ in health and IBS, which could have
      practical implications for future research. AIM: To examine reactivity to images
      in health and IBS. METHODS: Twelve paintings of IBS were shown to 70 patients to
      determine the four most evocative images. The spontaneous response to these
      images and four 'non-IBS painful' and four neutral paintings was assessed in
      another 100 IBS patients and 100 controls. The prompted reaction in terms of
      whether an image evoked the notion of pain, bloating or discomfort and to what
      degree was also recorded. RESULTS: Four images depicting bloating and pain scored
      the highest. These IBS images triggered significantly different reactivity
      between patients and controls in terms of their spontaneous and prompted
      responses. Even 'non-IBS painful' and neutral images resulted in exaggerated and
      frequently significantly different responses in patients than in controls.
      CONCLUSIONS: Visual hypersensitivity appears to be another manifestation of the
      tendency of IBS patients to react adversely to a variety of endogenous and
      exogenous stimuli. Identifying how individuals relate to different images might
      also give useful insights into understanding gastrointestinal symptoms.

PMID- 19744135
TI  - Is there a need for long-term follow-up in chronic idiopathic polyneuropathy?
AB  - OBJECTIVE: To evaluate the long-term functional status and well-being in patients
      with chronic idiopathic polyneuropathy (CIP) in comparison to Guillain-Barre
      syndrome (GBS) and healthy controls. MATERIALS AND METHODS: Forty-two CIP and 42
      GBS-patients were examined at median 5 and 6 years after disease onset and were
      compared with 50 healthy controls. The Fatigue Severity Scale (FSS), Visual
      Analogue Scale for pain (VAS), Disability Rating Index (DRI) and Medical Outcome
      Study 36-item short-form health status scale (SF-36) were used. Variables at
      onset and symptoms at follow-up were correlated with outcome measurements in GBS.
      RESULTS: Patients with CIP and GBS had more pain and disability than healthy
      controls. Additionally, CIP-patients were more fatigued than healthy controls.
      Patients with CIP were more fatigued [FSS 4.9 (SD 1.6) vs 3.8 (SD 1.8); P < 0.01]
      and disabled [DRI 4.1 (SD 2.3) vs 2.5 (SD 2.1); P = 0.05] than those with GBS.
      Physical functioning on the SF-36 was more impaired in CIP than GBS, compared
      with healthy controls. CONCLUSIONS: Patients with CIP and GBS seem to develop
      persistent impairment on long-term functional status and well-being, more clearly
      in CIP, reflecting the importance of long-term follow-up in further disease
      management.

PMID- 19744136
TI  - A novel mutation in the mitochondrial tRNA for tryptophan causing a late-onset
      mitochondrial encephalomyopathy.
AB  - BACKGROUND: Mitochondrial DNA (mtDNA) mutations are increasingly being recognized
      as causes of late-onset disease. We report a patient with a late-onset
      mitochondrial encephalomyopathy caused by a novel G > C transition in mtDNA at
      position 5556 in the gene encoding the tRNA for tryptophan (MTTW). AIMS: To
      investigate the cause of disease and assess the pathogenicity of this new
      mutation. METHODS: Clinical, histopathological and gene sequencing studies.
      Quantification of the mutation was performed in different tissues from the
      patient and two relatives and in single muscle fibres. RESULTS: The mutation was
      heteroplasmic, segregated in biochemically affected muscle fibres and was absent
      in blood. The level of mutation in skeletal muscle was higher than in brain,
      although the brain was clinically the most affected tissue. DISCUSSION: The 5556G
      > C mutation appears sporadic. It was not found in any of the family members
      tested, although some of them manifested disorders that can be associated with
      mtDNA disease. In addition to reporting the eighth mutation in MTTW, our case
      illustrates the challenges posed when assigning pathogenicity to mtDNA mutations.

PMID- 19744137
TI  - Parkinson's disease and hospital admissions: frequencies, diagnoses and costs.
AB  - OBJECTIVE: To evaluate the frequencies, causes and costs related to hospital
      admissions for patients with Parkinson's disease (PD) and controls. METHODS: In a
      prospective cohort study, 108 patients with PD from a population-based prevalence
      study and 854 age- and sex-matched controls were followed regarding admissions to
      the Stavanger University Hospital over a period of 12 years. RESULTS: There was
      no significant difference regarding the number of patients admitted, number of
      admissions or length of stay between the two cohorts. Based on 2005 prices, the
      costs per person year of survival were EUR 3288 for patients with PD and EUR 2466
      for control individual with incremental costs of EUR 822. However, the difference
      in costs was not statistically significant. The two cohorts had a different
      distribution of diagnoses causing hospital admissions. Patients with PD were more
      often admitted for PD-related symptoms and falls, while vascular disorders and
      cancer were substantially more common in control individuals. CONCLUSION:
      Hospitalization in PD does not induce incremental costs. The diagnoses causing
      hospital admissions were different in patients with PD as compared with controls.
      Our results indicate that cancer and vascular diseases might be less common in
      patients with PD than in the general population.

PMID- 19744138
TI  - The combinations of TNFalpha-308 and IL-6 -174 or IL-10 -1082 genes polymorphisms
      suggest an association with susceptibility to sporadic late-onset Alzheimer's
      disease.
AB  - OBJECTIVE: Single nucleotide polymorphisms in the regulatory regions of the
      cytokine genes for tumor necrosis factor alpha (TNFalpha), interleukin (IL)-6 and
      IL-10 have been suggested to influence the risk of Alzheimer's disease (AD) with
      conflicting results. AIM: To investigate the TNFalpha-308, IL-6 -174 and IL-10 
      1082 gene polymorphisms as susceptibility factors for AD. METHODS: We analyzed
      genotype and allele distributions of these polymorphisms in 101 sporadic AD
      patients and 138 healthy controls. RESULTS: Heterozygotes (AG) or combined
      genotype (AG+AA) for IL-10 -1082 were associated with approximately two-fold
      increase in the risk of AD. Carriers of A alleles of both TNFalpha-308 and IL-10 
      1082 had 6.5 times higher risk for AD in comparison with non-carriers.
      Concomitant presence of both mutant TNFalpha-308 A and IL-6 -174 C alleles raised
      three-fold the AD risk, whereas there was no notable risk for AD afflicted by IL
      6 -174 polymorphism alone. CONCLUSION: Our results suggest that TNFalpha and IL
      10 promoter polymorphism might be a risk factor for AD. The combined effects of
      TNFalpha-308, IL-6 -174 and IL-10 -1082 variant alleles may be more decisive to
      induce functional differences and modify the risk for AD.

PMID- 19744139
TI  - Computer-delivered interventions to reduce college student drinking: a meta
      analysis.
AB  - AIMS: This meta-analysis evaluates the efficacy of computer-delivered
      interventions (CDIs) to reduce alcohol use among college students. METHODS: We
      included 35 manuscripts with 43 separate interventions, and calculated both
      between-group and within-group effect sizes for alcohol consumption and alcohol
      related problems. Effects sizes were calculated for short-term (< or =5 weeks)
      and long-term (> or =6 weeks) intervals. All studies were coded for study
      descriptors, participant characteristics and intervention components. RESULTS:
      The effects of CDIs depended on the nature of the comparison condition: CDIs
      reduced quantity and frequency measures relative to assessment-only controls, but
      rarely differed from comparison conditions that included alcohol-relevant
      content. Small-to-medium within-group effect sizes can be expected for CDIs at
      short- and long-term follow-ups; these changes are less than or equivalent to the
      within-group effect sizes observed for more intensive interventions. CONCLUSIONS:
      CDIs reduce the quantity and frequency of drinking among college students. CDIs
      are generally equivalent to alternative alcohol-related comparison interventions.

PMID- 19744140
TI  - Microtubule binding and trapping at the tip of neurites regulate tau motion in
      living neurons.
AB  - During the development of neurons, the microtubule-associated tau proteins show a
      graded proximo-distal distribution in axons. In tauopathies such as Alzheimer's
      disease, tau accumulates in the somatodendritic compartment. To scrutinize the
      determinants of tau's distribution and motion, we constructed photoactivatable
      green fluorescent protein (GFP)-tagged tau fusion proteins and recorded their
      distribution after focal activation in living cells. Simulation showed that the
      motion of tau was compatible with diffusion/reaction as opposed to active
      transport/reaction. Effective diffusion constants of 0.7-0.8 microm(2)/second
      were calculated in neurites of PC12 cells and primary cortical neurons.
      Furthermore, tau's amino terminal projection domain mediated binding and
      enrichment of tau at distal neurites indicating that the tip of a neurite acts as
      an adsorber trapping tau protein. Treatment with taxol, incorporation of disease
      related tau modifications, experimentally induced hyperphosphorylation and
      addition of preaggregated amyloid beta peptides (Abeta) increased the effective
      diffusion constant compatible with a decreased binding to microtubules. Distal
      enrichment was present after taxol treatment but was suppressed at disease
      relevant conditions. The data suggest that (i) dynamic binding of tau to
      microtubules and diffusion along microtubules and (ii) trapping at the tip of a
      neurite both contribute to its distribution during development and disease.

PMID- 19744141
TI  - Altered motor activity of alternative splice variants of the mammalian kinesin-3
      protein KIF1B.
AB  - Several mammalian kinesin motor proteins exist as multiple isoforms that arise
      from alternative splicing of a single gene. However, the roles of many motor
      protein splice variants remain unclear. The kinesin-3 motor protein KIF1B has
      alternatively spliced isoforms distinguished by the presence or absence of
      insertion sequences in the conserved amino-terminal region of the protein. The
      insertions are located in the loop region containing the lysine-rich cluster,
      also known as the K-loop, and in the hinge region adjacent to the motor domain.
      To clarify the functions of these alternative splice variants of KIF1B, we
      examined the biochemical properties of recombinant KIF1B with and without
      insertion sequences. In a microtubule-dependent ATPase assay, KIF1B variants that
      contained both insertions had higher activity and affinity for microtubules than
      KIF1B variants that contained no insertions. Mutational analysis of the K-loop
      insertion revealed that variants with a longer insertion sequence at this site
      had higher activity. However, the velocity of movement in motility assays was
      similar between KIF1B with and without insertion sequences. Our results indicate
      that splicing isoforms of KIF1B that vary in their insertion sequences have
      different motor activities.

PMID- 19744142
TI  - Quantitative trait loci with effects on feed efficiency traits in Hereford x
      composite double backcross populations.
AB  - Two half-sib families of backcross progeny were produced by mating F(1) Line 1
      Hereford (L1) x composite gene combination (CGC) bulls with L1 and CGC cows. Feed
      intake and periodic weights were measured for 218 backcross progeny. These
      progenies were genotyped using 232 microsatellite markers that spanned the 29
      BTA. Progeny from L1 and CGC females was analysed separately using composite
      interval mapping to find quantitative trait loci (QTL) affecting daily dry matter
      intake (DMI), average daily gain (ADG), feed conversion (FCR) and residual feed
      intake (RFI). Results from both backcrosses were pooled to find additional QTL.
      In the backcross to L1, QTL were detected for RFI and DMI on BTA11, FCR on BTA16,
      and ADG on BTA9. In the backcross to CGC, QTL were detected for RFI on BTA10, FCR
      on BTA12 and 16 and ADG on BTA15 and 17. After pooling, QTL were detected for RFI
      on BTA 2, 6, 7, 10, 11, 13 and 16; for FCR on BTA 9, 12, 16, 17 and 21; for ADG
      on BTA 9, 14, 15, 17; and for DMI on BTA 2, 5, 6, 9, 10, 11, 20 and 23.

PMID- 19744143
TI  - Multiple maternal origins of native modern and ancient horse populations in
      China.
AB  - To obtain more knowledge of the origin and genetic diversity of domestic horses
      in China, this study provides a comprehensive analysis of mitochondrial DNA
      (mtDNA) D-loop sequence diversity from nine horse breeds in China in conjunction
      with ancient DNA data and evidence from archaeological and historical records. A
      247-bp mitochondrial D-loop sequence from 182 modern samples revealed a total of
      70 haplotypes with a high level of genetic diversity. Seven major mtDNA
      haplogroups (A-G) and 16 clusters were identified for the 182 Chinese modern
      horses. In the present study, nine 247-bp mitochondrial D-loop sequences of
      ancient remains of Bronze Age horse from the Chifeng region of Inner Mongolia in
      China (c. 4000-2000a bp) were used to explore the origin and diversity of Chinese
      modern horses and the phylogenetic relationship between ancient and modern
      horses. The nine ancient horses carried seven haplotypes with rich genetic
      diversity, which were clustered together with modern individuals among
      haplogroups A, E and F. Modern domestic horse and ancient horse data support the
      multiple origins of domestic horses in China. This study supports the argument
      that multiple successful events of horse domestication, including separate
      introductions of wild mares into the domestic herds, may have occurred in
      antiquity, and that China cannot be excluded from these events. Indeed, the
      association of Far Eastern mtDNA types to haplogroup F was highly significant
      using Fisher's exact test of independence (P = 0.00002), lending support for
      Chinese domestication of this haplogroup. High diversity and all seven mtDNA
      haplogroups (A-G) with 16 clusters also suggest that further work is necessary to
      shed more light on horse domestication in China.

PMID- 19744144
TI  - Recombination is suppressed over a large region of the rainbow trout Y
      chromosome.
AB  - The previous genetic mapping data have suggested that most of the rainbow trout
      sex chromosome pair is pseudoautosomal, with very small X-specific and Y-specific
      regions. We have prepared an updated genetic and cytogenetic map of the male
      rainbow trout sex linkage group. Selected sex-linked markers spanning the X
      chromosome of the female genetic map have been mapped cytogenetically in normal
      males and genetically in crosses between the OSU female clonal line and four
      different male clonal lines as well as in outcrosses involving outbred OSU and
      hybrids between the OSU line and the male clonal lines. The cytogenetic maps of
      the X and Y chromosomes were very similar to the female genetic map for the X
      chromosome. Five markers on the male maps are genetically very close to the sex
      determination locus (SEX), but more widely spaced on the female genetic map and
      on the cytogenetic map, indicating a large region of suppressed recombination on
      the Y chromosome surrounding the SEX locus. The male map is greatly extended at
      the telomere. A BAC clone containing the SCAR (sequence characterized amplified
      region) Omy-163 marker, which maps close to SEX, was subjected to shotgun
      sequencing. Two carbonyl reductase genes and a gene homologous to the vertebrate
      skeletal ryanodine receptor were identified. Carbonyl reductase is a key enzyme
      involved in production of trout ovarian maturation hormone. This brings the
      number of type I genes mapped to the sex chromosome to six and has allowed us to
      identify a region on zebrafish chromosome 10 and medaka chromosome 13 which may
      be homologous to the distal portion of the long arm of the rainbow trout Y
      chromosome.

PMID- 19744145
TI  - Molecular analysis of carbohydrate N-acetylgalactosamine 4-O sulfotransferase 8
      (CHST8) as a candidate gene for bovine spongiform encephalopathy susceptibility.
AB  - Endogenous prion proteins (PrP) play the central role in the pathogenesis of
      transmissible spongiform encephalopathies. The carbohydrate N-acetylgalactosamine
      4-O sulfotransferase 8 (CHST8) promotes the conversion of the cellular PrP(C)
      into the pathogenic PrP(d). Six sequence variants within the CHST8 gene were
      identified by comparative sequencing and genotyped for a sample of 623 animals
      comprising bovine spongiform encephalopathy (BSE)-affected and healthy control
      cows representing German Fleckvieh (German Simmental), German Holstein (Holstein
      Friesian) and Brown Swiss. Significant differences in the allele, genotype and
      haplotype frequencies between BSE-affected and healthy cows indicate an
      association of sequence variant g.37254017G>T with the development of the disease
      in Brown Swiss cattle.

PMID- 19744146
TI  - IL7RA polymorphisms and chronic inflammatory arthropathies.
AB  - The C allele of a single nucleotide polymorphism (SNP), rs6897932, located in the
      interleukin-7 receptor alpha chain (IL7RA) was recently found to be associated
      with multiple sclerosis and Type I diabetes. We analysed 13 SNPs in the IL7RA
      gene in a combined cohort of patients with chronic inflammatory arthropathies
      (rheumatoid arthritis and juvenile idiopathic arthritis; 368 patients and 532
      unaffected subjects). No significant associations with disease were found with
      the exception of the non-synonymous SNP rs6897932. This SNP showed modest
      enrichment of the TT genotype in arthritic patients compared with controls [P =
      0.02; OR 1.72 (95% CI 1.08-2.75)]. Our data are suggestive for a role of
      rs6897932 in predisposition to chronic inflammatory arthropathies.

PMID- 19744147
TI  - Thirty-six novel HLA alleles: 7 HLA-A, 11 HLA-B, 15 HLA-C and 3 HLA-DRB1.
AB  - Thirty-six novel human leukocyte antigen (HLA) alleles are described in this
      article: A*9225N, A*9234, A*030106, A*0337, A*2317, A*2480, A*3023; B*070206,
      B*0759, B*0761, B*0765, B*150106, B*1827, B*352002, B*3585, B*3943, B*4082,
      B*5151; Cw*0342, Cw*0343, Cw*0344, Cw*0428, Cw*0430, Cw*0433, Cw*050104, Cw*0519,
      Cw*060203, Cw*070109, Cw*070202, Cw*0750, Cw*0815, Cw*120306, Cw*1409; DRB1*0336,
      DRB1*0473 and DRB1*1382.

PMID- 19744148
TI  - Seeking safe and efficacious anemia management.

PMID- 19744149
TI  - What's next after fistula first: is an arteriovenous graft or central venous
      catheter preferable when an arteriovenous fistula is not possible?
AB  - Findings from observational studies have established that the arteriovenous
      fistula (AVF) is the preferred form of vascular access for chronic hemodialysis.
      Unfortunately, in a subset of patients with end-stage renal disease, an AVF
      cannot be placed or fails to mature. In these patients an alternate form of
      vascular access, either an arteriovenous graft (AVG) or central venous catheter
      (CVC) must be selected. In this review we discuss the findings and limitations of
      studies examining the effect of access type (AVG or CVC) on clinical endpoints
      including mortality, quality of life, occurrence of infections, as well as the
      impact of the different access types on resource requirements. Specifically, we
      examine whether findings from previous studies are valid and applicable to
      patients for whom an AVF is not possible, and outline the need for future
      randomized clinical trials addressing this question.

PMID- 19744150
TI  - Use of warfarin in people with low glomerular filtration rate or on dialysis.
AB  - Atrial fibrillation, venous thromboembolism, and access malfunction are common
      clinical problems in dialysis patients that prompt consideration of warfarin
      therapy. Atrial fibrillation appears to be more common in people with low
      glomerular filtration rate (GFR) or on dialysis than in the general population,
      but the risk of stroke in this population is not known. No randomized trials have
      addressed the safety and efficacy of warfarin in these patients. Deep venous
      thrombosis and pulmonary embolism are also more common in this population and,
      again, no randomized trials have addressed the safety and efficacy of warfarin in
      this group. Pending such information, we suggest an approach that generalizes
      from large randomized controlled trials in the general population, modifying the
      assessment of risks and benefits for individual patients using the CHADS(2) and
      HEMORR(2)HAGES scores. A single randomized trial reported a clinically important
      benefit in prevention of catheter malfunction from warfarin and low-molecular
      weight heparin started within 12 hours of catheter insertion, in the prevention
      of catheter thrombosis, in people treated with ticlopidine. Trials of low
      intensity anticoagulation for people with grafts and of fixed 1 mg daily warfarin
      dosing in people with catheters showed no benefit. Warfarin substantially
      increases the risk of bleeding in patients on dialysis. It is possible that it
      may contribute also to accelerated vascular calcification. Large randomized
      studies are needed to assess the risk-benefit ratio of warfarin in people with
      low GFR or on dialysis for a range of indications.

PMID- 19744151
TI  - Excimer laser assisted angioplasty in hemodialysis access intervention.
AB  - A case is described in which an excimer laser is used to assist angioplasty of a
      severe central venous lesion that is refractory to conventional techniques.
      Modern laser technology uses the ultraviolet (UV) spectral region to generate
      nanosecond pulses of energy. This results in photoablation, which is the process
      by which energy photons cause molecular bond disruption, while minimizing thermal
      damage to the surrounding vascular tissues. Further investigation of excimer
      laser assisted angioplasty in the setting of hemodialysis access intervention is
      needed to rigorously define its potential role. In occlusive disease where no
      conventional alternative is available, however, laser therapy is a viable option.

PMID- 19744152
TI  - Can chronic volume overload be recognized and prevented in hemodialysis patients?
      The critical role of treatment time.

PMID- 19744153
TI  - Can chronic volume overload be recognized and prevented in hemodialysis patients?
      Preventing intradialytic hypotension.

PMID- 19744154
TI  - Can chronic volume overload be recognized and prevented in hemodialysis patients?
      Use of a restricted-salt diet.

PMID- 19744155
TI  - Can chronic volume overload be recognized and prevented in hemodialysis patients?
      The pitfalls of the clinical examination in assessing volume status.

PMID- 19744156
TI  - Can chronic volume overload be recognized and prevented in hemodialysis patients?
      Newer methods to assess volume status.

PMID- 19744157
TI  - Biological evaluation of 2-(4-amino-phenyl)-3-(3,5-dihydroxylphenyl) propenoic
      acid.
AB  - 2-(4-Aminophenyl)-3-(3,5-dihydroxylphenyl) propenoic acid (CSN-07001) is a new
      compound based on the combination of resveratrol and propenoic acid derivatives.
      In vitro cyclooxygenase (COX)/5-lipoxygenase (5-LOX) inhibition assays showed
      that the test compound exhibited a dual inhibitory activity against the COX (COX
      1 IC(50) = 2.20 microM, COX-2 IC(50) = 1.76 microM) and 5-LOX (IC(50) = 0.28
      microM) enzymes. Further, the enhanced COX-1/COX-2/5-LOX expression in
      lipopolysaccaride-induced lung inflammation in mice was also suppressed by CSN
      07001 in a concentration-dependent manner. In vivo studies showed that CSN-07001
      exhibited potent anti-inflammatory and antinociceptive effects in different
      experimental models. We further examined the risk of gastric damage induced by
      CSN-07001. The test compound was gastric-sparing in that it elicited markedly
      fewer stomach lesions than indomethacin in rats. Taken together, our data
      indicate that CSN-07001 exhibits a novel class of dual inhibitors of COX and 5
      LOX having therapeutic potential as non-steroidal anti-inflammatory agents with
      an enhanced gastric safety profile.

PMID- 19744158
TI  - Visuo-spatial processing and the N1 component of the ERP.
AB  - Asymmetries in posterior ERP components, such as the N1, are generally taken to
      reflect the visual processing of spatial information in absolute (fixation-based)
      coordinates. Yet, it is also well established that the position of an object can
      be coded relative to the position of other objects. To examine the ERP correlates
      of relative spatial coding, two experiments were conducted in which spatially
      neutral target stimuli were preceded, accompanied, or followed by laterally
      presented, task-irrelevant accessory stimuli. Targets presented simultaneously
      with a lateral accessory evoked, despite physical asymmetry, a bilateral,
      symmetric N1. Targets that followed the accessory evoked, despite physical
      symmetry, an asymmetric N1, with a maximum contralateral to the accessory N1.
      Thus, lateralizations in the N1 range already reflect relative spatial coding
      rather than just the processing of the absolute location of incoming information.

PMID- 19744159
TI  - Chronic constriction injury induces aquaporin-2 expression in the dorsal root
      ganglia of rats.
AB  - Aquaporins are a family of water channel proteins involved in water homeostasis
      in several tissues. Current knowledge of aquaporin expression in the nervous
      system is very limited. Therefore the first aim of this study was to assess, by
      immunohistochemistry and immunoblotting analysis, the presence and localization
      of aquaporin-2 in the spinal cord and dorsal root ganglia of naive adult rats. In
      addition, we evaluated aquaporin-2 expression in response to chronic constriction
      injury of the sciatic nerve, a model of neuropathic pain. Our results showed that
      aquaporin-2 expression was not detectable either in the spinal cord or the dorsal
      root ganglia of naive rats. However, we showed for the first time an increase of
      aquaporin-2 expression in response to chronic constriction injury treatment in
      small-diameter dorsal root ganglia neurons but no expression in the lumbar spinal
      cord. These data support the hypothesis that aquaporin-2 expression is involved
      in inflammatory neuropathic nerve injuries, although its precise role remains to
      be determined.

PMID- 19744160
TI  - Phytochrome-mediated growth inhibition of seminal roots in rice seedlings.
AB  - In rice (Oryza sativa) seedlings, continuous white-light irradiation inhibited
      the growth of seminal roots but promoted the growth of crown roots. In this
      study, we examined the mechanisms of photoinhibition of seminal root growth.
      Photoinhibition occurred in the absence of nitrogen but increased with increasing
      nitrogen concentrations. In the presence of nitrogen, photoinhibition was
      correlated with coiling of the root tips. The seminal roots were most
      photosensitive 48-72 h after germination during the 7-day period after
      germination. White-light irradiation for at least 6 h was required for
      photoinhibition, and the Bunsen-Roscoe law of reciprocity was not observed.
      Experiments with phytochrome mutants showed that far-red light was perceived
      exclusively by phyA, red light was perceived by both phyA and phyB, and phyC had
      little or no role in growth inhibition or coiling of the seminal roots. These
      results also suggest that other blue-light photoreceptors are involved in growth
      inhibition of the seminal roots. Fluence-response curve analyses showed that phyA
      and phyB control very low-fluence response and low-fluence response,
      respectively, in the seminal roots. This was essentially the same as the growth
      inhibition previously observed at the late stage of coleoptile development (80 h
      after germination). The photoperceptive site for the root growth inhibition
      appeared to be the roots themselves. All three phytochrome species of rice were
      detected immunochemically in roots.

PMID- 19744161
TI  - Deficiency in a cytosolic ribose-5-phosphate isomerase causes chloroplast
      dysfunction, late flowering and premature cell death in Arabidopsis.
AB  - The oxidative pentose phosphate pathway (oxPPP) is part of central metabolism,
      consisting of two distinct phases: the oxidative phase and the non-oxidative
      phase. The non-oxidative phase of the oxPPP generates carbon skeletons for the
      synthesis of nucleotides, aromatic amino acids, phenylpropanoids and their
      derivatives, which are essential for plant growth and development. However, it is
      not well understood how the non-oxidative phase of the oxPPP contributes to plant
      growth and development. Here, we report the characterization of Arabidopsis T-DNA
      knockout mutants of the RPI2 gene (At2g01290), which encodes a cytosolic ribose-5
      phosphate isomerase (RPI) that catalyzes the reversible interconversion of
      ribulose-5-phosphate and ribose-5-phosphate in the non-oxidative phase of the
      oxPPP. Although recombinant Arabidopsis RPI2 protein exhibits marked RPI
      enzymatic activity, knockout of the RPI2 gene does not significantly change the
      total RPI activity in the mutant plants. Interestingly, knockout of RPI2
      interferes with chloroplast structure and decreases chloroplast photosynthetic
      capacity. The rpi2 mutants accumulate less starch in the leaves and flower
      significantly later than wild-type when grown under short-day conditions.
      Furthermore, the rpi2 mutants display premature cell death in the leaves when
      grown at an above-normal temperature (26 degrees C). These results demonstrate
      that a deficiency in the non-oxidative phase of the cytosolic oxPPP has
      pleiotropic effects on plant growth and development and causes premature cell
      death.

PMID- 19744163
TI  - Effect of octreotide on polycystic liver volume.

PMID- 19744164
TI  - Antifibrotic effect of angiotensin blockers in hypertensive hepatitis C patients.

PMID- 19744165
TI  - An uncommon cause of massive scrotal enlargement.

PMID- 19744166
TI  - Significance of antibodies to soluble liver/liver pancreas antigen: experiences
      in Germany.

PMID- 19744167
TI  - Hypoxia inducible factor-1 alpha induction by tumour necrosis factor-alpha, but
      not by toll-like receptor agonists, modulates cellular respiration in cultured
      human hepatocytes.
AB  - BACKGROUND/AIMS: Genes encoding for some of the mitochondrial proteins are under
      the control of the transcriptional factor hypoxia inducible factor-1 alpha (HIF-1
      alpha), which can accumulate under normoxic conditions in inflammatory states.
      The aim of this study was to evaluate the effects of cobalt chloride (CoCl(2), a
      hypoxia mimicking agent), tumour necrosis factor-alpha (TNF-alpha) and toll-like
      receptor (TLR) -2, -3 and -4 agonists on HIF-1 alpha accumulation, and further on
      HIF-1 alpha-mediated modulation of mitochondrial respiration in cultured human
      hepatocytes. METHODS: The human hepatoma cell line HepG2 was used in this study.
      Cells were treated with CoCl(2), TNF-alpha and TLR-2, -3 and -4 agonists. HIF-1
      alpha was determined by Western blotting and mitochondrial respiration in
      stimulated cells by high-resolution respirometry. RESULTS: CoCl(2), TNF-alpha and
      TLR agonists induced the expression of HIF-1 alpha in a time-dependent fashion.
      TNF-alpha and CoCl(2), but not TLR agonists, induced a reduction in complex I-,
      II- and IV-dependent mitochondrial oxygen consumption. TNF-alpha-associated
      reduction of cellular oxygen consumption was abolished through inhibition of HIF
      1 alpha activity by chetomin (CTM). Pretreatment with cyclosporine A prevented
      CoCl(2)-induced reduction of complex I- and II-dependent mitochondrial oxygen
      consumption and TNF-alpha-induced reduction of complex-I-dependent respiration,
      implicating the involvement of the mitochondrial permeability transition pore
      openings. TNF-alpha and TLR-2, -3 and -4 agonists induced the expression of
      vascular endothelial growth factor, which was partially abolished by the blockage
      of HIF-1 alpha with CTM. CONCLUSIONS: The data suggest that HIF-1 alpha modulates
      mitochondrial respiration during CoCl(2) and TNF-alpha stimulation, whereas it
      has no effect when induced with TLR-2, -3 and -4 agonists.

PMID- 19744168
TI  - Postural and dynamic masseter and anterior temporalis muscle EMG repeatability in
      serial assessments.
AB  - Electromyographic (EMG) assessment has been used as a non-invasive tool to
      objectively assess muscle function, although with controversial research and
      clinical potential. The aim of this study was to assess within-, inter-subject
      and between-day repeatability of serial EMG recordings. The study sample included
      10 asymptomatic subjects with no history of temporomandibular disorders or muscle
      parafunctions. Bilateral masseter and anterior temporalis muscle EMG parameters
      were assessed in two standardized serial recordings (day 1 to day 2) using a
      portable EMG equipment (ME 6000 recorder, Mega Electronics, Kuopio, Finland). The
      functional tasks included postural/resting activities as pre- and post-recording
      series of 30 s each and jaw opening/closing, intercuspal and maximal voluntary
      clenching activities of 5 s, repeated three times. The assessed EMG parameters
      included the mean amplitude, s.d. and error. In addition, the power spectrum EMG
      parameter assessment included the median power frequencies and the averaged EMG
      spectrum data values. The results of the intraclass correlation coefficient
      analysis indicated reliability for nearly all of the intercuspal and all
      clenching EMG amplitude and power spectrum parameters. This was complemented by
      the repeated measures anova and post hoc analyses that indicated non-significant
      differences between day 1 and 2 in task- and muscle-related analyses. Most
      variability was noted in postural and some in opening/closing tasks. In
      conclusion this study assessed the reliability, repeatability and limitations of
      postural and various dynamic masseter and temporalis EMG recordings for serial
      assessment.

PMID- 19744169
TI  - Foreign body urethral obstruction in a chimpanzee (Pan troglodytes).
AB  - BACKGROUND: A 34-year-old, captive-born, vasectomized male chimpanzee (Pan
      troglodytes) presented with lethargy and scrotal swelling. METHODS: Urethral
      obstruction was diagnosed via urethroscopy. RESULTS: Removal of the grass stem
      foreign body resolved the obstruction. Scrotal and preputial ulceration developed
      from urine scald, which was managed with surgical debridement and antibiotics.
      CONCLUSIONS: After 7 weeks, the animal was reintroduced to its troup and has been
      healthy for 11 months.

PMID- 19744170
TI  - Findings and risk factors of early mortality of endoscopic retrograde
      cholangiopancreatography in different cohorts of elderly patients.
AB  - OBJECTIVES: To analyze experience of endoscopic retrograde
      cholangiopancreatography (ERCP) in patients with of different age cohorts and
      discuss the risk factors of early mortality after ERCP. DESIGN: Retrospective
      study. SETTING: Tertiary care medical center. PARTICIPANTS: Two hundred sixty
      four patients with pancreatobiliary diseases divided into cohorts according to
      decades as young-old (YO, 65-74, n=143), old-old (OO, 75-84, n=88), and very-old
      (VO, >or=85, n=33). MEASUREMENTS: The indications, results, and complications of
      ERCP in these three groups were demonstrated and compared. RESULTS: Three hundred
      three ERCP procedures were performed. The leading indication for ERCP was common
      bile duct (CBD) obstruction or dilation. Diabetes mellitus was significantly more
      prevalent in the YO group (39.2%) than in the other two groups (OO, 15.9%; VO,
      24.2%; P=.001). The most common finding of ERCP was CBD dilatation. There was no
      difference in incidence of malignant diseases between the three groups. Acute
      pancreatitis was the most frequently identified post-ERCP complication. There was
      no significant difference in early mortality between the three cohorts. Patients
      with malignancy had higher early mortality than those with benign disease (71.4%
      vs 11.2%; P=.001). CONCLUSION: The findings and incidences of complication of
      ERCP in different elderly cohorts were similar. Underlying malignancy seemed to
      bear some relation to early mortality after the ERCP procedure.

PMID- 19744171
TI  - RUNX2 mutations in cleidocranial dysplasia patients.
AB  - OBJECTIVE: Mutations in the RUNX2 gene, a master regulator of bone formation,
      have been identified in cleidocranial dysplasia (CCD) patients. CCD is a rare
      autosomal-dominant disease characterized by the delayed closure of cranial
      sutures, defects in clavicle formation, and supernumerary teeth. The purposes of
      this study were to identify genetic causes of two CCD nuclear families and to
      report their clinical phenotypes. MATERIALS AND METHODS: We identified two CCD
      nuclear families and performed mutational analyses to clarify the underlying
      molecular genetic etiology. RESULTS: Mutational analysis revealed a novel
      nonsense mutation (c.273T>A, p.L93X) in family 1 and a de novo missense one
      (c.673C>T, p.R225W) in family 2. Individuals with a nonsense mutation showed
      maxillary hypoplasia, delayed eruption, multiple supernumerary teeth, and normal
      stature. In contrast, an individual with a de novo missense mutation in the Runt
      domain showed only one supernumerary tooth and short stature. CONCLUSIONS:
      Mutational and phenotypic analyses showed that the severity of mutations on the
      skeletal system may not necessarily correlate with that of the disruption of
      tooth development.

PMID- 19744172
TI  - Dental status of Portuguese HIV+ patients and related variables: a multivariate
      analysis.
AB  - OBJECTIVE: The aim of this cross-sectional study was to evaluate the dental
      status of 101 Portuguese HIV+ subjects aged 22-71 years (mean = 39) and its
      association with clinical, socioeconomic, and behavioral variables. MATERIALS AND
      METHODS: A calibrated dentist performed clinical examination and collected data
      on dental caries, periodontal status, dental plaque levels, prosthetic
      conditions, and need. The volunteers completed questionnaires on socioeconomic
      and behavioral variables as well as the Oral Health Impact Profile (OHIP-14)
      questionnaire. Univariate and multiple logistic regression (MLR) analyses were
      performed. RESULTS: The mean number of decayed, missing or filled teeth index
      (DMFT index) was 16.44, standard deviation (s.d.) = 8.42. MLR demonstrated that
      salaried employee and those with OHIP-14 <or=4.22, or any/no dental plaque were
      less prone to have DMFT > median (=17). As regards prosthetic status, 28.8% of
      the examined individuals used dental prosthesis. MLR demonstrated that HIV+ with
      DMFT >17 or those who knew they were HIV-positive for longer than 5 years were
      more prone to need dental prostheses. The mean OHIP-14 index was 5.83 (s.d. =
      7.79). CONCLUSIONS: The dental health status of HIV-infected Portuguese patients
      was unsatisfactory and related to clinical, socioeconomic, and behavioral
      variables.

PMID- 19744173
TI  - The influence of handheld mobile phones on human parotid gland secretion.
AB  - BACKGROUND: Handheld mobile phones (MPHs) have become a 'cultural' accessory
      device, no less so than a wrist watch. Nevertheless, the use of MPHs has given
      rise to great concern because of possible adverse health effects from exposure to
      the radiofrequency radiation (RFR) emitted by the device. Previous studies
      suggested correlation between MPH and salivary gland tumors. OBJECTIVE: To
      evaluate whether MPH induces physiologic changes in the adjacent parotid gland,
      located on the dominant side, in terms of secretion rates and protein levels in
      the secreted saliva. MATERIALS AND METHOD: Stimulated parotid saliva was
      collected simultaneously from both glands in 50 healthy volunteers whose MPH use
      was on a dominant side of the head. RESULTS: A significantly higher saliva
      secretion rate was noticed in the dominant MPH side compared with that in the non
      dominant side. Lower total protein concentration was obtained in the dominant
      compared with the non-dominant MPH side among the right dominant MPH users.
      CONCLUSIONS: Parotid glands adjacent to handheld MPH in use respond by elevated
      salivary rates and decreased protein secretion reflecting the continuous insult
      to the glands. This phenomenon should be revealed to the worldwide population and
      further exploration by means of large-scale longitudinal studies is warranted.

PMID- 19744174
TI  - Chemical peels in aesthetic dermatology: an update 2009.
AB  - BACKGROUND/OBJECTIVES: Peelings are among the oldest and most widespread
      aesthetic procedures used in aesthetic dermatology worldwide. More than 50
      commercial peelings are currently available on the European market. MATERIALS AND
      METHODS: In the present review, we summarise the current knowledge on chemical
      peels. RESULTS/CONCLUSIONS: A state-of-the-art peeling procedure will take into
      account the depth of the targeted structure and the skin condition of the patient
      to choose carefully among the variables such as chemical class of the peeling
      agent, concentration, frequency and pressure of the application. The usual
      classification of chemical peels comprises superficial, medium and deep peels.
      For superficial peels alpha-hydroxy-acids and most recently lipo-hydroxy acid are
      used to induce an exfoliation of the epidermis. Medium-depth agents such as
      trichloroacetic acid (<50%) cause an epidermal to papillary dermal peel and
      regeneration. Deep peels using trichloroacetic acid (>50%) or phenol based
      formulations reach the reticular dermis to induce dermal regeneration. The
      success of any peel is crucially dependent on the physicians understanding of the
      chemical and biological processes, as well as of indications, clinical
      effectiveness and side effects of the procedures.

PMID- 19744175
TI  - Five-year experience in the treatment of alopecia areata with DPC.
AB  - BACKGROUND: The effectiveness of Diphencyprone (DPC) in alopecia areata (AA) was
      demonstrated in several studies with highly variable response rates ranging from
      5% to 85%. OBJECTIVE: The response rate and variable factors affecting the
      prognosis were studied focusing on long-term follow-up with or without
      maintenance therapy. METHODS: A total of 135 cases of AA were treated with DPC.
      Patients were divided into five groups according to the area of scalp affected:
      Grade 1 AA: 25-49% scalp affection; Grade 2 AA: 50-74% scalp affection; Grade 3
      AA: 75-99% scalp affection; alopecia totalis and alopecia universalis. An initial
      response was defined as appearance of new terminal hair within treated sites.
      Excellent response was defined as terminal hair covering >75% of the scalp.
      Relapse meant >25% hair loss. Maintenance therapy meant ongoing therapy once
      every 1-4 weeks after excellent response. Follow-up was performed to detect any
      relapse of AA. RESULTS: Ninety-seven patients continued therapy for >or=3 months.
      After an initial 3 month lag, cumulative excellent response was seen in 15
      patients (15.4%), 47 patients (48.5%), 51 patients (52.6%) and 55 patients
      (55.7%) after 6, 12, 18 and 24 months respectively in a mean median time of 12
      months. The only patient variable affecting the prognosis was baseline extent of
      AA. Excellent response was seen in 100%, 77%, 54%, 50% and 41% in Grade 1, Grade
      2, Grade 3, AA totalis and AA universalis patients respectively. Side-effects
      were few and tolerable. Hair fall >25% occurred in 17.9% of patients on
      maintenance and 57.1% of patients without maintenance therapy (P-value=0.025).
      CONCLUSION: Diphencyprone is an effective and safe treatment of extensive AA. A
      long period of therapy is needed and will increase the percentage of responders
      especially in alopecia totalis and universalis. Maintenance therapy is
      recommended to reduce the risk of relapse.

PMID- 19744176
TI  - Interstitial granulomatous dermatitis with arthritis associated with trastuzumab.

PMID- 19744177
TI  - Familiar occurrence of multiple primary epidermoid cysts and trichostasis
      spinulosa: a novel skin phenotype associated with inherited sensorineural
      deafness.

PMID- 19744178
TI  - Growth rate of human fingernails and toenails in healthy American young adults.
AB  - BACKGROUND: Human nail clippings are increasingly used in epidemiological studies
      as biomarkers for assessing diet and environmental exposure to trace elements or
      other chemical compounds. However, little is known about the growth rate of human
      nails. OBJECTIVE: To estimate the average growth rate of fingernails and toenails
      and examine factors that may influence nail growth rate. METHODS: Twenty-two
      healthy American young adults marked their nails close to the proximal nail fold
      with a provided nail file following a standardized protocol, and recorded the
      date and the distance from the proximal nail fold to the mark. One to three
      months later, participants recorded the date and distance from the proximal nail
      fold to the mark again. Nail growth rate was calculated based on recorded
      distance and time between the two measurements. RESULTS: Average fingernail
      growth rate was faster than that of toenails (3.47 vs. 1.62 mm/month, P < 0.01).
      There was no significant difference between right and left fingernail/toenail
      growth rates. The little fingernail grew slower than other fingernails (P <
      0.01); the great toenail grew faster than other toenails (P < 0.01). Younger age,
      male gender, and onychophagia were associated with faster nail growth rate;
      however, the differences were not statistically significant. CONCLUSION: Nail
      growth rates have increased compared with previous estimates conducted decades
      ago. Toenail clippings may reflect a long exposure time frame given the
      relatively slow growth rate.

PMID- 19744179
TI  - Clinical and laboratory study of rosacea in northern Greece.
AB  - BACKGROUND: Numerous factors have been implicated in the pathogenesis of rosacea,
      which remains obscure. OBJECTIVES: To examine the epidemiological characteristics
      of rosacea patients, the histopathological alterations, the prevalence of gastric
      Helicobacter pylori infection and the role of ultraviolet radiation, to detect
      the presence of Demodex folliculorum on affected skin and to elucidate the
      immunological nature of this disorder. METHODS: The study included 100 patients
      with rosacea. Each patient was assessed with a clinical, haematological,
      biochemical and histological examination; serology test for the detection of
      antibodies against H. pylori; direct immunofluorescence on perilesional, sun
      exposed skin and indirect immunofluorescence with monkey oesophagus as a
      substrate; antinuclear antibody titre and a skin surface biopsy to search for
      Demodex folliculorum. RESULTS: Women were more frequently affected. Half of our
      patients were 51-70 years old. About two-thirds were photo-types I and II and 73%
      complained of worsening of conditions after sun exposure. An almost permanent
      histopathological feature was solar elastosis. Higher prevalence of H. pylori was
      not established. Prevalence and mean density of Demodex folliculorum were
      significantly increased in rosacea patients. Direct and indirect
      immunofluorescence tests were positive in 6.4% and 6.7% respectively. Antinuclear
      antibody titres were found in 21.1%. CONCLUSIONS: Our results suggest the pivotal
      role of chronic sun exposure in the pathogenesis of rosacea. Demodex folliculorum
      represents a significant cofactor that may contribute to the transition of the
      disease from a vascular to an inflammatory stage. The low positive results of
      direct and indirect immunofluorescence do not support a potential autoimmune role
      in the development of rosacea.

PMID- 19744180
TI  - Epidermal Langerhans cells in actinic prurigo: a comparison between lesional and
      non-lesional skin.

PMID- 19744181
TI  - Soluble immune receptor serum levels are associated with age, but not with
      clinical phenotype or disease severity in childhood atopic dermatitis.
AB  - BACKGROUND: Soluble immune receptors (SIRs) have been proposed as biomarkers in
      patients with atopic dermatitis (AD). However, their clinical applicability in
      affected children has rarely been studied. OBJECTIVE: To assess the diagnostic
      usefulness of serum SIRs in childhood AD by correlating the obtained receptor
      profiles with serological parameters and clinical features such as age, AD
      phenotype and disease severity. METHODS: We investigated 100 children with AD.
      The sCD14, sCD23, sCD25, sCD30, total IgE (tIgE) and eosinophilic cationic
      protein (ECP) were determined using sera of all children. The clinical phenotype
      was classified as extrinsic AD (ADe) or intrinsic AD (ADi) by the presence of
      allergen-specific IgE antibodies. RESULTS: A total of 55 male and 45 female
      children were recruited. The sCD23, sCD25 and sCD30 serum levels revealed
      significant age-dependency. At a mean SCORAD of 40 (range 8-98), none of the
      evaluated SIRs was correlated to disease severity. In all, 73% of patients
      suffered from ADe while 27% showed the ADi phenotype. None of the analysed SIRs
      differed significantly between ADe and ADi patients, while tIgE and ECP levels
      were elevated in the ADe subgroup. CONCLUSION: The current study provides
      evidence that sCD23, sCD25 and sCD30 serum levels are highly age-dependent. Serum
      concentrations of all investigated SIRs did not significantly correlate with
      disease severity in children with AD and were not differentially expressed in
      patients of different AD phenotypes. Therefore, we believe that the studied SIRs
      cannot be regarded as clinically useful biomarkers for the assessment of
      childhood AD.

PMID- 19744182
TI  - The association between prenatal cocaine exposure and physiological regulation at
      13 months of age.
AB  - BACKGROUND: This study examined the association between prenatal cocaine exposure
      (PCE) and autonomic regulation at 13 months of age. METHODS: Measures of
      respiratory sinus arrhythmia (RSA) were obtained from 156 (79 exposed, and 77
      nonexposed) infants during baseline and during tasks designed to elicit positive
      (PA) and negative affect (NA). RESULTS: There was a significant suppression of
      RSA during the negative affect task for nonexposed infants but not for exposed
      infants. Maternal symptoms of depression or anxiety (MDA) did not mediate this
      association. However, gender and MDA did moderate this association such that
      exposed boys and exposed infants whose mothers had higher levels of MDA had an
      increase in RSA during a task designed to elicit NA rather than the typical
      pattern of RSA suppression. CONCLUSIONS: These results suggest that there are
      several possible pathways from PCE to physiological dysregulation during late
      infancy.

PMID- 19744183
TI  - Children's patterns of emotional reactivity to conflict as explanatory mechanisms
      in links between interpartner aggression and child physiological functioning.
AB  - BACKGROUND: This paper examined children's fearful, sad, and angry reactivity to
      interparental conflict as mediators of associations between their exposure to
      interparental aggression and physiological functioning. METHODS: Participants
      included 200 toddlers and their mothers. Assessments of interparental aggression
      and children's emotional reactivity were derived from maternal surveys and a semi
      structured interview. Cortisol levels and cardiac indices of sympathetic nervous
      system (SNS) and parasympathetic nervous system (PNS) activity were used to
      assess toddler physiological functioning. RESULTS: Results indicated that toddler
      exposure to interparental aggression was associated with greater cortisol levels
      and PNS activity and diminished SNS activity. Toddler angry emotional reactivity
      mediated associations between interparental aggression and cortisol and PNS
      functioning. Fearful emotional reactivity was a mediator of the link between
      interparental aggression and SNS functioning. CONCLUSIONS: The results are
      interpreted within conceptualizations of how exposure and reactivity to family
      risk organize individual differences in physiological functioning.

PMID- 19744184
TI  - Immunosuppression and atypical infections in CML patients treated with dasatinib
      at 140 mg daily.
AB  - BACKGROUND: The multikinase inhibitor dasatinib exerts growth-inhibitory effects
      in patients with imatinib-resistant chronic myeloid leukaemia (CML). In first
      clinical trials, side effects of dasatinib, 140 mg daily, were reported to be
      mild and tolerable. PATIENTS AND METHODS: We examined the side effect profile in
      16 patients with imatinib-resistant CML who received 140 mg dasatinib daily in
      our center. RESULTS: Dasatinib produced substantial and sometimes severe or even
      life-threatening side effects with > or = 10% body weight loss (6/16 patients),
      pleural effusions grade II or higher (12/16) and infectious complications
      (12/16), including atypical infections not seen in imatinib-treated patients. One
      patient developed Epstein-Barr-Virus-positive mucosal leucoplakia, one died from
      pneumonia caused by pneumocystis carinii and three patients developed a skin
      cancer. Most events were recorded within the first 2 years of therapy, only skin
      tumours developed after the second year. In ex vivo experiments performed in
      dasatinib-treated patients, transient suppression of IgE-dependent activation of
      blood basophils and TcR-dependent activation of T-lymphocytes was found.
      Moreover, in drug-binding studies, dasatinib was found to bind to several key
      kinase-targets of the immune system including Lyn and Btk, in mast cell,
      basophil, B-cell and T-cell lines. CONCLUSION: Dasatinib acts not only anti
      neoplastic in CML but may also act as an immunosuppressive agent when applied at
      140 mg daily, and produces frequent pleural effusions and weight loss in advanced
      CML.

PMID- 19744185
TI  - CDKs as therapeutic targets for the human genetic disease tuberous sclerosis?
AB  - The tuberous sclerosis gene 2 product tuberin is an important regulator of the
      mammalian target of rapamycin (mTOR). In addition, tuberin is known to bind to
      the cyclin-dependent kinase (CDK) inhibitor p27(Kip1) (p27) and to regulate its
      stability and localization via mTOR-independent mechanisms. Recently, evidence
      has been provided that tuberin also affects p27 localization via regulating
      mTOR's potential to activate the serum- and glucocorticoid-inducible kinase
      (SGK1) to phosphorylate p27. Taken together, these findings strengthen the
      argument that besides mTOR-inhibitors, such as rapamycin analogues, p27 and CDKs
      could also be considered targets for hamartoma therapeutics in tuberous
      sclerosis.

PMID- 19744186
TI  - The use of p63 as an effective immunomarker in the diagnosis of pulmonary
      squamous cell carcinomas on de-stained bronchial lavage cytological smears.
AB  - OBJECTIVES: A diagnosis in pulmonary onco-cytopathology primarily necessitates
      distinguishing small cell carcinoma (SCLC) from non-small cell carcinoma (NSCLC),
      which includes squamous cell carcinoma and adenocarcinoma. Lately, p63 antibody
      has been used for distinguishing squamous cell carcinoma from SCLC and
      adenocarcinoma. We present an analysis of p63 expression in cytological smears
      from 100 bronchial lavage specimens comprising 51 cases of SCLC and 49 cases of
      NSCLC. METHODS: A single Papanicolaou-stained conventional smear was de-stained
      and re-fixed with cold acetone and methanol for immunocytochemical staining with
      p63 antibody. Staining results were graded as 0 (nil), 1+ (focal), 2+ (moderate,
      diffuse) and 3+ (strong, diffuse). RESULTS: Out of 100 cases, 21 were
      cytologically diagnosed as squamous cell carcinoma. Twenty of these showed 2+ or
      3+ p63 positivity, whereas one, which was adenocarcinoma on histology, showed 1+
      staining. Of seven cases cytologically diagnosed as adenocarcinoma, six showed no
      p63 staining, whereas one, which was squamous cell carcinoma on histology, showed
      1+ staining. All 48 cases cytologically diagnosed as SCLC were confirmed as such
      on histology and showed no p63 staining. Four cases were cytologically designated
      as poorly differentiated carcinomas, of which three showed no p63 staining and
      one showed 3+ staining. The former three were found to be SCLC on histology while
      the latter was squamous cell carcinoma. The remaining 20 cases were cytologically
      designated as NSCLC. Of these, eight showed no p63 staining, whereas 10 showed 1+
      and two showed 2+ staining. The former eight were adenocarcinoma on histology and
      the latter two were squamous cell carcinoma. The 10 cases that showed 1+ p63
      staining were adenocarcinomas (n = 5), squamous cell carcinoma (n = 4) and NSCLC,
      not otherwise specified (n = 1). Positive staining was seen in normal basal
      cells, which acted as an internal control. Overall sensitivity of p63 for
      squamous cell carcinoma was 100% and specificity was 90.4%. CONCLUSIONS: p63
      immunostaining on processed cytology smears can be used to help identify squamous
      cell carcinoma. Its diffuse expression was specific for squamous cell carcinoma
      while focal staining was also seen in adenocarcinoma.

PMID- 19744187
TI  - Anaplastic large cell lymphoma: a critical evaluation of cytomorphological
      features in seven cases.
AB  - OBJECTIVE: Anaplastic large cell lymphoma (ALCL) is a rare subtype of non
      Hodgkin's lymphoma that is difficult to diagnose on fine needle aspiration
      cytology (FNAC). Detailed descriptions about the cytomorphological features of
      ALCL are few and do not illustrate the various categories of cells, which we have
      done in this study. METHODS: Eight FNAC specimens from seven patients with biopsy
      proven ALCL over a period of 6 years were reviewed. Cytomorphological details
      were analysed and the various cell types identified were enumerated on
      Papanicolaou and May-Grunwald-Giemsa (MGG)-stained smears. RESULTS: Of the seven
      cases, five were of conventional type, one of the lymphohistiocytic variant and
      one of the small cell variant. Aspiration from the conventional type showed a
      mixed population of lymphoid cells with many plasma cells. The tumour cells were
      intricately admixed within and distributed as single cells without grouping.
      Distinct hallmark cells, doughnut cells, embryo cells, tennis racket cells, cells
      with wreath-like nuclei, Reed-Sternberg-like cells and nondescript cells were
      seen. Nucleoli were rounded, occasionally tubular in shape. The tumour cells
      showed abundant blue cytoplasm on MGG stain with a perinuclear hoff. Aspiration
      from the lymphohistiocytic and small cell variants showed a small number of
      similar characteristic giant cells. All cases were confirmed as ALK-1 positive.
      CONCLUSIONS: The morphological spectrum of ALCL is wide and it may be
      misdiagnosed as a metastatic poorly differentiated malignant tumour on FNAC.
      Identification of unusual giant cells on FNAC helps in establishing a diagnosis
      on an early lymph node biopsy.

PMID- 19744188
TI  - Gamna-Gandy bodies from cardiac myxoma on intraoperative cytology.

PMID- 19744189
TI  - Role of fine needle aspiration cytology in the diagnosis and management of
      Warthin's tumour of the salivary glands.
AB  - OBJECTIVE: Local excision surgical procedures and non-surgical conservative
      management are considered alternatives to superficial parotidectomy in the
      treatment and management of Warthin's tumour (WT). Such therapeutic alternatives
      demand accurate diagnosis. In order to determine whether fine needle aspiration
      cytology (FNAC) is capable of rendering such a minimally invasive diagnosis, we
      evaluated its accuracy and diagnostic parameters in a large series of
      histologically proven cases of WT. METHODS: A cytohistological study of 116
      salivary tumours from 110 patients (four WT were bilateral) with a histological
      or cytological diagnosis of WT. RESULTS: Histology confirmed the cytological
      diagnosis in 103 of 114 tumours (90.4%). Two tumours were incorrectly diagnosed
      on cytology as WT. In 11 cases of WT there was an erroneous or non-representative
      cytological diagnosis. The sensitivity was 90.4%, and positive predictive value
      98.1%. Regarding malignancy, there were three misdiagnoses. One tumour diagnosed
      as WT was a low-grade mucoepidermoid carcinoma. Two cases considered 'suspicious
      of squamous cell carcinoma' corresponded to WT. After review, 81.3% of the cases
      of WT were considered typical and 18.7% non-typical; all misdiagnoses were in the
      latter group. Cytological difficulties could be divided into three areas: (i)
      absence of one or more diagnostic components; (ii) 'squamoid' pattern; and (iii)
      mucinous metaplasia. Degenerated oncocytes were present in 65% of cases.
      CONCLUSIONS: FNAC offers the possibility of a reliable diagnosis of WT.
      Pathologists must pay attention to the squamous appearance of degenerated
      oncocytes. Cytology, when coupled with clinical and image findings, may permit
      conservative tumour management.

PMID- 19744190
TI  - Epithelioid cell granuloma in CSF cytology.

PMID- 19744191
TI  - Evaluation of accuracy of fine needle aspiration cytology in BI-RADS3 category
      breast lesions: cytohistological correlation in 337 cases.
AB  - OBJECTIVE: To evaluate the accuracy of fine needle aspiration cytology (FNAC) in
      BI-RADS3 breast lesions. METHODS: Between January 2004 and December 2007, 337
      cases from BI-RADS3 lesions underwent FNAC. Three to six needle passes were made
      on each patient. In 67 cases (20%) a histological biopsy was performed.
      Cytological and histological interpretations were performed by the same
      pathologist. RESULTS: The histological diagnosis showed that 88% (59/67) of BI
      RADS3 breast lesions were benign. Only 6% (4/67) were malignant, consisting of
      ductal carcinoma in situ and infiltrating ductal carcinoma. CONCLUSION: BI-RADS3
      lesions remain disruptive in their management. However, the correlation between
      cytology and histology showed that most of these lesions were benign and that
      finally FNAC remains a useful and accurate test in the management of these
      lesions.

PMID- 19744192
TI  - Clinical nurse specialists' approaches in selecting and using evidence to improve
      practice.
AB  - ABSTRACT Background: Evidence-based practice (EBP) has become the desired
      standard within all health disciplines because the integration of the best
      evidence into clinical practice is fundamental to optimizing patient outcomes.
      The valuing of research and research-based knowledge as the basis for decision
      making is explicit in current discourse in the health sciences. Despite the
      desires of proponents of EBP for use of evidence derived through research, nurses
      prefer to use knowledge derived from experience and social interactions. The
      clinical nurse specialist (CNS) is in the ideal position to act as a link between
      evidence and practice; however, a paucity of knowledge exists on how CNSs select
      and use evidence in their daily practice. PURPOSE: The purpose of this
      descriptive, cross-sectional study was to examine the approaches used by CNSs to
      select and use evidence in their daily practice. METHOD: A telephone survey,
      developed for this study from a pilot study conducted by the principal
      investigator (PI), was used to elicit responses from a purposive sample of CNSs
      living in a western Canadian province who were willing to be contacted for
      research, and who had practiced clinically as CNSs within the past year. A
      response rate of 75% (n = 94) was achieved. Descriptive statistics were used to
      describe and compare the variables of interest. RESULTS: Literature tailored to
      particular specialties and personal experiences were reported as the most
      frequently accessed sources of evidence. This evidence was most often used to
      facilitate improvements in patient care, and least often used to develop further
      research proposals. CONCLUSION: This study indicates that although CNSs select
      and use evidence from a wide variety of sources, further development of their
      capacity to retrieve and transfer knowledge may increase the uptake of research
      findings in nursing practice.

PMID- 19744193
TI  - A new blood group system, RHAG: three antigens resulting from amino acid
      substitutions in the Rh-associated glycoprotein.
AB  - BACKGROUND AND OBJECTIVES: Rh-associated glycoprotein (RhAG) is closely
      associated with the Rh proteins in the red cell membrane. Two high frequency
      antigens (Duclos and DSLK) and one low frequency antigen (Ol(a)) have serological
      characteristics suggestive of expression on RhAG. MATERIALS AND METHODS: RHAG was
      sequenced from the DNA of one Duclos-negative, one DSLK-negative, and two Ol(a+)
      individuals. Recombinant protein was expressed in HEK 293 cells. Protein models
      with RhAG subunits were constructed. RESULTS: The original Duclos-negative
      patient was homozygous for RHAG 316C>G, encoding Gln106Glu. HEK 293 cells
      expressing Gln106Glu mutant RhAG did not react with anti-Duclos. An individual
      with DSLK-negative red cells was homozygous for 490A>C, encoding Lys164Gln. Two
      Ol(a+) members of the original Norwegian family were heterozygous for 680C>T,
      encoding Ser227Leu. A Japanese donor with Rh(mod) phenotype had Ol(a+) red cells
      and was homozygous for 680C>T. CONCLUSION: The three red cell antigens encoded by
      RHAG form the RHAG blood group system: Duclos is RHAG1 (030001); Ol(a) is RHAG2
      (030002); and DSLK is provisionally RHAG3 (030003).

PMID- 19744194
TI  - Assessing the safety and efficacy of a test-based, targeted donor screening
      strategy to minimize transfusion transmitted malaria.
AB  - BACKGROUND AND OBJECTIVES: In 2005, the Australian Red Cross Blood Service
      implemented a malaria antibody testing based strategy for donors with a history
      of travel/residence in a malaria endemic country or a past history of malaria.
      This report assesses the safety and efficacy of the strategy since inception.
      MATERIALS AND METHODS: Eligible blood donors were tested using the Newmarket
      malarial antibody EIA at least 4 months after their last potential exposure.
      Where EIA non-reactive their quarantined red cells were considered for
      transfusion and they were re-instated for cellular component manufacture at their
      next donation. The efficiency and safety of this strategy were evaluated based on
      the additional number of components recovered for transfusion and the observed
      incidence of transfusion transmitted malaria (TTM) respectively. RESULTS: Of the
      repeat reactive donors, 2696 (> 99.99%) were PCR negative whilst one was PCR
      positive with very low level parasitaemia. The average number of RBCs and
      platelets recovered per annum was 64 967 and 7398 representing 7.9 and 5.5%
      respectively of their annual production. No new TTM cases were recorded and the
      observed TTM rate of zero was consistent with the upper 95% CI for the pretesting
      TTM incidence of 0.9 per million donations. CONCLUSION: The study findings
      support the efficacy and safety of a targeted screening strategy combining a
      sensitive antibody screening test with a 4-month cellular component restriction
      period for donors with a declared malarial risk. The TTM risk in Australia
      remains low and did not measurably change after implementing the testing
      strategy.

PMID- 19744195
TI  - Early loading after 21 days of healing of nonsubmerged titanium implants with a
      chemically modified sandblasted and acid-etched surface: two-year results of a
      prospective two-center study.
AB  - PURPOSE: The aim of this two-center study was to evaluate screw-type titanium
      implants with a chemically modified, sandblasted and acid-etched surface when
      placed in the posterior maxilla or mandible, and loaded 21 days after placement.
      MATERIAL AND METHODS: All 56 patients met strict inclusion criteria and provided
      informed consent. Each patient displayed either a single-tooth gap, an extended
      edentulous space, or a distal extension situation in the posterior mandible or
      maxilla. Eighty-nine dental implants (SLActive, Institut Straumann AG, Basel,
      Switzerland) were inserted according to an established nonsubmerged protocol and
      underwent undisturbed healing for a period of 21 days. Where appropriate, the
      implants were loaded after 21 days of healing with provisional restorations in
      full occlusion. Definitive metal ceramic restorations were fabricated and
      positioned on each implant after 6 months of healing. Clinical measurements
      regarding soft tissue parameters and radiographs were obtained at different time
      points up to 24 months after implant placement. RESULTS: Of the 89 inserted
      implants, two (2.2%) implants failed to integrate and were removed during
      healing, and two (2.2%) additional implants required a prolonged healing time. A
      total of 85 (95.6%) implants were therefore loaded without incident after 21 days
      of healing. No additional implant was lost throughout the study period, whereas
      one implant was lost to follow-up and therefore left unaccounted for further
      analysis. The remaining 86 implants all exhibited favorable radiographic and
      clinical findings. Based on strict success criteria, these implants were
      considered successfully integrated 2 years after insertion, resulting in a 2-year
      success rate of 97.7%. CONCLUSION: The results of this prospective two-center
      study demonstrate that titanium implants with a modified SLA surface can
      predictably achieve successful tissue integration when loaded in full occlusion
      21 days after placement. Integration could be maintained without incident for at
      least 2 years of follow-up.

PMID- 19744196
TI  - Histomorphometric analysis of human maxillary sinus lift with a new bone
      substitute biocomposite: a preliminary report.
AB  - PURPOSE: To analyze radiographic and histological outcomes of maxillary sinus
      floor augmentation using a calcium-sulfate based allograft containing
      demineralized bone matrix particles. MATERIALS AND METHODS: Fifteen maxillary
      sinus lift procedures with simultaneous placement of titanium implants were
      performed in 12 patients of both genders aged 36-71 years. Each sinus cavity was
      filled by the biocomposite. After 3 months of healing, all surgical sites were
      uncovered and bone biopsies were retrieved for undecalcified histology and
      histomorphometry. The ratio between the original and the grafted sinus height
      (GSH/OSH) was computed using a panoramic radiography taken immediately after
      surgery and at 3 months of healing, and the two ratios were compared by Wilcoxon
      signed-rank test. RESULTS: By 3 months, all implants were stable without clinical
      and radiographic signs of infection. Significant changes in GSH/OSH during
      healing were seen (2.7 +/- 0.6 initially vs. 2.6 +/- 0.5 after healing; p =
      0.01). Histologic findings showed newly formed bone surrounding the residual
      grafted particles without inflammation. At 3 months, mean regenerated bone
      density was 33.8 +/- 8.6%; marrow spaces amounted to 32.3 +/- 10.3%; residual
      graft was 33.9 +/- 9.0%. Similar histomorphometric and radiographic results were
      obtained independently from patient age or sex. CONCLUSIONS: The analysed putty
      seems to be a safe and effective graft material for maxillary sinus floor
      augmentation by accelerating bone regeneration and thus reducing the healing
      time.

PMID- 19744197
TI  - The effects of superficial roughness and design on the primary stability of
      dental implants.
AB  - BACKGROUND: Primary implant stability has been used as an indicator for future
      osseointegration and whether an immediate/early loading protocol should be
      applied. Implant stability is the key to clinical success. PURPOSE: The aim of
      this work was to analyze the influence of the design and surface morphology on
      the primary stability of dental implants. The insertion torque and resonance
      frequency analysis (RFA) were the parameters used to measure the primary
      stability of the implants. MATERIALS AND METHODS: Thirty implants, divided in six
      groups of five samples were placed in cylinder of high molecular weight
      polyethylene. The groups were different upon two designs (cylindrical and conic)
      and three implant surfaces finishing (machined, acid etched, and anodized). The
      insertion torque was quantified by a digital torque driver (Lutron Electronic
      Enterprise Co., Taipei, Taiwan) and the resonance frequency was measured by
      Osstell mentorTM (Integration Diagnostics AB, Goteborg, Sweden). The implant
      surface morphology was characterized by scanning electron microscopy, roughness
      measurement, and friction coefficient. RESULTS: The machined implants showed
      smaller insertion torques than treated implant surfaces. There were no
      differences between the RFA measurements in all tested surfaces. Statistical
      analyses demonstrated no correlation between the dental implant insertion torque
      and primary stability measured by the RFA. The implants with treated surfaces
      showed greater roughness, a higher friction coefficient, and demanded a larger
      insertion torque than machined implants. The results of the surface roughness and
      friction coefficients are in accordance with the results of the insertion torque.
      The difference, across the insertion torque values, between conical and
      cylindrical implants, can be explained by the different contact surface area
      among the thread geometry of these implants. CONCLUSION: The maximum implant
      insertion torque depends on the implant geometry, thread form, and implant
      surface morphology. The placement of conical implants with treated surfaces
      required the highest insertion torque. There was no correlation between RFA and
      insertion torque implant.

PMID- 19744198
TI  - Local sinus lift for single-tooth implant. I: clinical and radiographic follow
      up.
AB  - BACKGROUND: For single-tooth implant replacement in the posterior maxilla, it is
      often necessary to do an augmentation of the alveolar process because of post
      extraction resorption and include part of the maxillary sinus. PURPOSE: The
      purpose of this study is to present a technique for a local sinus lift with
      autogenous bone in a one-stage procedure. Additionally, volume changes of the
      grafted area were evaluated radiographically up to 2 years. MATERIALS AND
      METHODS: Twenty patients, 12 female and 8 males, were included in the study.
      Single-tooth replacement was made in the second premolar area in 7 cases and in
      the molar area in 13 cases. Local sinus lift and implant installation were made
      simultaneously. Abutment connection was made after 6 months of healing. RESULTS:
      Two years of clinical and radiographic follow-ups have been made in all patients.
      The survival rate was 100%. The residual bone volume in the actual area was 2-5
      mm preoperatively, after sinus lifting in mean 13 mm, after 1 year in mean 11.4
      mm, and 2 years postoperatively in mean 10.6 mm. CONCLUSIONS: Local sinus lift
      with simultaneous bone augmentation and single-tooth replacement in the posterior
      maxilla is a predictable method although a certain bone volume reduction around
      the implant was evident at the 2-year follow-up.

PMID- 19744199
TI  - Clinical outcome and bone preservation of single TiUniteTM implants installed
      with flapless or flap surgery.
AB  - BACKGROUND: Flapless, free-handed implant surgery offers advantages for patient
      comfort, but studies on long-term clinical success based on marginal bone loss
      are scarce. AIM: The aim of this study was to compare single implants installed
      with a flap (F) or flapless (FL) surgery with respect to survival and marginal
      bone preservation after at least 3 years. MATERIALS AND METHODS: Fifty-three
      TiUniteTM Branemark implants, installed in 49 patients (27 females; 22 males;
      mean age 53 years) were examined. Then, 25 F and 28 FL were delayed loaded; bone
      level from the abutment-implant level was measured on intraoral radiographs. From
      44 (21 F, 23 FL), 31 (18F, 13 FL), and 36 (18 F, 18 FL) implants, radiographs
      were available at baseline and after 1 and 3 years of function. RESULTS: The
      overall survival rate was 100% and the overall mean bone loss after an average of
      38 months was 1.35 mm (SD 0.91; range 0-3.7). Both F and FL showed increasing
      bone loss during the first year with a higher bone loss for FL than for F sites
      (p < .01). Afterward, no further bone loss occurred and both groups were
      statistically equal (p > .7). On individual implant level, nearly 80% in both F
      and FL were considered a success showing bone loss between 1.5 and 1.9 mm.
      CONCLUSIONS: Single implants yield an excellent prognosis with stable bone levels
      irrespective of the surgical technique, and free-handed flapless surgery is a
      viable alternative to more extensively planned guided surgery. Proper case
      selection and clinical experience are considered prerequisites for a predictable
      treatment outcome.

PMID- 19744200
TI  - The effect of smoking on early bone remodeling on surface modified Southern
      Implants(r).
AB  - INTRODUCTION: Smoking affects the survival of turned titanium implants. Although
      smoking has less impact on the failure rate of rough surface implants, the effect
      on bone loss on rough surface implants has not been studied yet and may be an
      important factor in biological stability. AIM: To determine the effect of smoking
      on early implant failures and bone remodeling around moderately rough implants
      (Southern Implants(r), Southern Implants, Irene, South Africa). MATERIALS AND
      METHODS: Three hundred twenty-nine patient records, containing information on 712
      installed implants, were scrutinized retrospectively and periapical radiographs
      were analyzed for interproximal bone level. Mann-Whitney U-test and Fisher's
      exact test were performed to compare bone level and implant survival in smokers
      and nonsmokers. Only implants with at least 6 months of function time were
      analyzed for bone level changes. RESULTS: The overall survival rate was 98.3%.
      Implants in smokers had a threefold higher failure rate compared with nonsmokers
      (5/104 = 4.8% vs 7/608 = 1.2%). This was statistically significant on implant
      level (p = .007) but not on patient level (1/41 vs 7/288, p = .997). Readable
      radiographs from 363 implants in 169 patients were available with a mean follow
      up of 12 months (SD 5.11; range 6-28). The mean interproximal bone level was 1.36
      mm (n = 363; SD 0.41; range 0.48-3.70). Bone levels were independent of jaw
      location. Sixty implants from 21 smokers lost statistically significantly (p =
      .001) more bone (mean 1.56; SD 0.53; range 0.75-3.22) than the 303 implants in
      148 nonsmokers (mean 1.32 mm; SD 0.38; range 0.48-3.7). The maxilla is especially
      prone to bone loss compared with the mandible (1.70 mm vs 1.26 mm, p < .001).
      CONCLUSION: The Southern Implants(r) system demonstrated a high absolute survival
      rate. Although smokers are not more prone to implant loss, more pronounced peri
      implant bone loss was observed, especially in the maxilla. Whether this affects
      future biological complications remains to be investigated in prospective long
      term studies.

PMID- 19744201
TI  - Care and aftercare related to implant-retained dental crowns in the maxillary
      aesthetic region: a 5-year prospective randomized clinical trial.
AB  - AIM: To prospectively assess surgical and prosthetic care and aftercare related
      to the placement of implant-retained dental crowns after local bone augmentation
      in patients missing one tooth in the maxillary aesthetic region. METHODS: Ninety
      three patients were randomly allocated to one of three local augmentation groups:
      (1) chin bone; (2) chin bone covered by a Bio-Gide(r) membrane (Geistlich,
      Wolhusen, Switzerland); and (3) Bio-Oss(r) covered by a Bio-Gide(r) membrane.
      After local augmentation, implant placement (ITI) and fabrication of an implant
      retained dental crown (cemented metal-ceramic dental crown) was performed.
      Prosthetic and surgical care and aftercare was scored from the first visit until
      5 years after the augmentation of the implant region. RESULTS: The need for care
      and aftercare was comparable between the local augmentation groups. Three
      implants were lost (5-year implant survival rate: 96.7%). Surgical aftercare was
      needed in 9% of patients and consisted of care related to peri-implant tissue
      problems. Prosthetic aftercare was needed more often: all patients needed
      periodic routine inspections; 63% needed supplemental oral hygiene support; and
      16% needed additional prosthetic care, mainly consisting of fabricating new
      crowns (12%). CONCLUSION: Placing an implant in the maxillary esthetic region
      after local bone augmentation is a safe and reliable treatment option not needing
      much specific aftercare other than periodic preventive routine inspections,
      routine oral hygiene care, and fabrication of a new crown in one out of every
      eight to nine patients in 5 years. The method used for augmentation was
      irrespective of the patients' need for aftercare.

PMID- 19744202
TI  - Cancellous bone block allografts for the augmentation of the anterior atrophic
      maxilla.
AB  - BACKGROUND: Pre-implant augmentative surgery is a prerequisite in many cases in
      the anterior maxilla to achieve a stable, long-term esthetic final result.
      PURPOSE: The aim of the present study was to evaluate the outcome of ridge
      augmentation with cancellous freeze-dried block bone allografts in the anterior
      atrophic maxilla followed by placement of dental implants. MATERIALS AND METHODS:
      Thirty-one consecutive patients were included in the study. A bony deficiency of
      at least 3 mm horizontally and up to 3 mm vertically according to computerized
      tomography (CT) served as inclusion criteria. Sixty-three implants were inserted
      after a healing period of 6 months. Nineteen of sixty-three implants were
      immediately restored. Bone measurements were taken prior to bone augmentation,
      during implant placement, and at second-stage surgery. RESULTS: Forty-six
      cancellous allogeneic bone blocks were used. The mean follow-up was 34 +/- 16
      months. Mean bone gain was 5 +/- 0.5 mm horizontally, and 2 +/- 0.5 mm
      vertically. Mean buccal bone resorption was 0.5 +/- 0.5 mm at implant placement,
      and 0.2 +/- 0.2 mm at second-stage surgery. Mean bone thickness buccal to the
      implant neck was 2.5 +/- 0.5 mm at implant placement, and 2.3 +/- 0.2 mm at
      second-stage surgery. There was no evidence of vertical bone loss between implant
      placement and second-stage surgery. Block and implant survival rates were 95.6
      and 98%, respectively. All patients received a fixed implant-supported
      prosthesis. CONCLUSION: Cancellous block allografts appear to hold promise for
      grafting the anterior atrophic maxilla.

PMID- 19744203
TI  - Blood-stained combat boots and acute pain medicine.

PMID- 19744205
TI  - Pharmacological management of persistent pain in older persons.

PMID- 19744206
TI  - Evolving pharmacological management of persistent pain in older persons.

PMID- 19744207
TI  - The evolution of pain medicine: residency training for health care reform.

PMID- 19744209
TI  - Chronic pain, smoking, and obesity: a pain physician's perspective on patient
      selection.

PMID- 19744211
TI  - Advanced regional anesthesia morbidity and mortality grading system: regional
      anesthesia outcomes reporting (ROAR).
AB  - OBJECTIVE: A regional anesthesia complication grading system (regional anesthesia
      outcomes reporting [ROAR]) was developed and applied to 1,213 consecutive
      patients over a 14-month period. The goal of the project was the creation of a
      system to standardize complication reporting in the regional anesthesia
      literature. DESIGN: Patient demographics, status as a war casualty, regional
      block procedure-specific details, and complication grade were entered into an
      Internet-based, encrypted Department of Defense database. Regional anesthesia
      complications were later graded and subcategorized depending on what phase of the
      block the procedural adverse event took place. RESULTS: One thousand ninety-eight
      (90.5%) patients had neither regional anesthesia associated technical
      difficulties or more severe complications. Of a total of 147 cases with adverse
      events among 115 patients (1.3 per patient), the majority (63.3%, 93/147) were
      low-grade complications resulting in no significant morbidity. The most common
      complications resulting in patient morbidity were failed block requiring catheter
      removal and/or supplemental block (35.4%, 17/48). High grade complications
      represented only 4.1% (6/147) of all peri-procedural morbidity. These
      complications included pneumothorax requiring tube thoracostomy, transient
      laryngeal nerve dysfunction, and cancellation of planned operation after
      peripheral nerve block or catheter placement. CONCLUSIONS: The value of the ROAR
      system is that it identifies important issues in risk management in regional
      anesthesia, thereby providing opportunities for further investigation and
      clinical practice refinement. Furthermore, it provides for a common language when
      reporting outcomes in the regional anesthesia literature. Use of the ROAR system
      will provide consistency in outcomes reporting and facilitate comparisons between
      methods and procedures.

PMID- 19744212
TI  - Response to: exercise performance and chronic pain in chronic fatigue syndrome:
      the role of pain catastrophizing.

PMID- 19744213
TI  - Neurogenetics can help turn pain concepts more objective.

PMID- 19744216
TI  - Radiofrequency neurotomy for a patient with deep brain stimulators: proposed
      safety guidelines.
AB  - OBJECTIVE: To discuss the potential risks inherent to performing radiofrequency
      procedures in patients with deep brain neurostimulators, and to propose safety
      guidelines. DESIGN: Case report. SETTING: Tertiary care teaching hospital.
      SUBJECT: A 67-year-old male with intractable back pain due to advanced lumbar
      spondylosis, with a history of advanced Parkinson's Disease requiring two deep
      brain stimulators. INTERVENTION: Radiofrequency neurotomy lumbar facet joints.
      RESULTS: No atypical symptoms were reported during the procedure that would
      indicate iatrogenic injury from radiofrequency effect on the deep brain
      neurostimulators. The subject's back pain was relieved by 70% for greater than 6
      months bilaterally. DISCUSSION: There are several theoretical concerns when using
      radiofrequency therapies on patients with neurostimulators. Our patient did not
      experience any known adverse events during or subsequent to the procedure. This
      article presents our proposed safety guidelines for using radiofrequency
      neurotomy on patients with deep brain stimulators. CONCLUSIONS: Radiofrequency
      medial branch neurotomy was performed on a patient with two deep brain
      stimulators with a satisfactory clinical outcome, and no adverse sequelae.
      Additional study is warranted regarding the safety and compatibility of brain
      neurostimulators and radiofrequency interventions.

PMID- 19744217
TI  - A unique presentation of complex regional pain syndrome type I treated with a
      continuous sciatic peripheral nerve block and parenteral ketamine infusion: a
      case report.
AB  - OBJECTIVE: To successfully treat a patient with complex regional pain syndrome,
      refractory to standard therapy, to enable a rapid and full return to professional
      duties. SETTING: This case report describes the rapid resolution of an unusual
      presentation of complex regional pain syndrome type I after four days of
      treatment with a continuous sciatic peripheral nerve block and a concomitant
      parenteral ketamine infusion. The patient was initially diagnosed with complex
      regional pain syndrome (CRPS) I of the right lower extremity following an ankle
      inversion injury. Oral medication with naproxen and gabapentin, as well as
      desensitization therapy, failed to provide any relief of her symptoms. She was
      referred to the interventional pain management clinic. A lumbar sympathetic block
      failed to provide any relief. The patient was diagnosed with CRPS I and was
      admitted for treatment with a continuous peripheral nerve block and parenteral
      ketamine. CONCLUSION: This case suggests therapeutic benefit from aggressive
      treatment of both the peripheral and central components of CRPS.

PMID- 19744218
TI  - Diseases mimicking allergic rhinitis.
AB  - Although allergic rhinitis is the commonest diagnosis in the child with nasal
      obstruction and rhinorrhoea, the differential must include other, much rarer,
      conditions. We present three case histories and discussion of several other
      diagnoses which should be considered.

PMID- 19744219
TI  - Current management of allergic rhinitis in children.
AB  - Over the last 20 years, there has been significant progress in our understanding
      of the pathophysiology of allergic rhinitis, including the discovery of new
      inflammatory mediators, the link between asthma and allergic rhinitis ('one
      airway-one disease' concept) and the introduction of novel therapeutic
      modalities. These new insights have been documented in the Allergic Rhinitis and
      its Impact on Asthma guidelines and have led to the creation of evidence-based
      management algorithms. We now understand the importance of a common strategy for
      treating allergic inflammation of the upper and lower airway as a way of
      improving outcome, reducing hospital admissions, providing better quality of life
      and perhaps, altering the natural course of the 'allergic march'. A therapeutic
      ladder is suggested: Whereas for mild intermittent allergic rhinitis, allergen
      avoidance should be the first line of treatment with subsequent addition of a
      second generation topical or oral antihistamine, nasal saline or cromoglycate, in
      cases of moderate to severe allergic rhinitis, a nasal steroid is the treatment
      of choice. If a patient with moderate/severe persistent allergic rhinitis fails
      to improve after 4 wk of adequate treatment, patient compliance or the diagnosis
      must be re-assessed. In such cases, when the diagnosis is in doubt, a careful
      clinical examination including nasal endoscopy is mandatory to assess for other
      potential causes of nasal obstruction. In children who suffer from concomitant
      allergic rhinitis and asthma, a management algorithm that addresses concurrently
      asthma and allergic rhinitis is vital, both from a theoretical and from a
      practical point of view: Parents overwhelmingly prefer a single strategy for the
      treatment of their child's upper and lower airway symptoms; however, the overall
      quality of life in children with severe asthma can be significantly improved if
      rhinitis is adequately addressed.

PMID- 19744220
TI  - Association of nutrient intake and wheeze or asthma in a Greek pre-school
      population.
AB  - The rise of asthma prevalence in children observed the last years might be
      related to several dietary factors/components as suggested by several
      researchers. We aimed to evaluate the potential relationship between certain
      nutrients intake and asthma occurrence in a population of pre-school children. In
      the framework of the cross-sectional study 'Growth, Exercise and Nutrition
      Epidemiological Study In pre-schoolers', data were collected from 1964 children,
      aged 24-72 months, living in five different counties in Greece. The International
      Study of Asthma and Allergies in Childhood questionnaire was used to assess
      asthma related outcomes. Dietary intake was assessed with 3 days diet records.
      The prevalence of ever wheeze, current wheeze and diagnosed asthma was 37.7%,
      27.5% and 10.5% respectively. Dietary intake of magnesium had a 0.5% and 0.6%
      increase in the reported risk of current wheeze and diagnosed asthma
      respectively. On the contrary a decrease in the prevalence of ever (OR: 0.997,
      95% CI: 0.995-1.000) and current wheeze (OR: 0.996, 95% CI: 0.993-0.999) was
      associated with vitamin C intake. Calcium intake slightly decreased the risk of
      current wheeze (OR: 0.999, 95% CI: 0.998-0.999). An increase of 2% of the risk of
      reporting ever or current wheeze was associated with mono-unsaturated fatty acid
      intake. Magnesium intake was the only independent predictor for doctor's
      diagnosed asthma. We conclude that dietary intake of vitamin C and calcium seem
      to have a protective effect on the incidence of wheeze in pre-school children,
      whereas magnesium and mono-unsaturated fatty acid may have a harmful role.

PMID- 19744221
TI  - Depressive symptoms amongst asthmatic children's caregivers.
AB  - We wanted to find out, whether the number of depressive symptoms is higher
      amongst asthmatic children's caregivers, compared to international data, to the
      Hungarian population average, and to parents of children with chronic renal
      disease. Are these depressive symptoms connected to the children's psychological
      status, asthma severity or current asthma symptoms? One-hundred and eight, 7- to
      17-yr-old asthmatic children were enrolled, who have been treated at the
      Semmelweis University, First Department of Pediatrics. Children were suffering
      from asthma for at least 1 yr, with a median of 8 yr (1-16 yr), they started to
      develop asthmatic symptoms between the age of 0.5-14 yr (median: 3 yr). We also
      identified 27 children with chronic renal diseases and their caregivers, who
      functioned as a control group. Children were asked to complete the Hungarian
      validated versions of the Child Depression Inventory, the Spielberger State
      Anxiety Inventory for Children and the Juniper Pediatric Asthma Quality of Life
      Questionnaire. Asthma severity and current symptoms were also documented, 56% had
      no symptoms on the preceding week. Caregivers were asked to complete the
      Hungarian versions of the Beck Depression Inventory (BDI) short form, the
      Spielberger Anxiety Inventory and the Juniper Pediatric Asthma Caregivers'
      Quality of Life Questionnaire. Caregivers of asthmatic children had significantly
      more depressive symptoms (7.73 +/- 6.69 s.d.) than the age-specific normal
      population (p < 0.01). Caregivers of renal patients also experience more
      depressive symptoms (9.61 +/- 7.43 s.d.) than their healthy peers, but difference
      between the two chronic diseases' group did not prove to be significant.
      Asthmatic children's caregivers who scored more points on the BDI than the
      population average suffer from more anxiety symptoms, but their quality of life
      is not worse than the caregivers' with less depressive points. Depressive
      symptoms were neither connected to the children's psychological and asthmatic
      symptoms nor quality of life. Amongst caregivers of asthmatic children, at least
      mild depressive symptoms were represented amongst 39% of men and 33% of women.
      Gender difference was not significant, despite observations in the normal
      Hungarian population. Amongst caregivers of renal patients, depressive symptoms
      were represented in 14% of men and 50% of women. Gender difference was
      significant. (p = 0.05). Significant difference was observed between male
      asthmatic and renal caregivers, albeit difference was not significant between the
      female groups. No difference was found in depressive symptoms according to
      caregivers' level of education. Caregivers of children with asthma have more
      depressive symptoms than the average Hungarian population, but their results do
      not differ from caregivers taking care of children with chronic renal diseases.
      Caregivers of asthmatic children having at least mild depressive symptoms tend to
      have higher anxiety symptoms as well. Up to date, childhood chronic disease
      management and long-term care should also focus on parental psychology, mainly on
      depression and anxiety, as prevalence is higher than in the average population.

PMID- 19744222
TI  - The association between early sensitization patterns and subsequent allergic
      disease. The DARC birth cohort study.
AB  - Prevention of allergic diseases depends on early identification of clinical
      markers preceding such disorders. This study describes the natural course of
      sensitization as measured by skin prick test (SPT) and specific immunoglobulin E
      (S-IgE) and analyses the association between early sensitization patterns and
      subsequent allergic disease at 6 yr of age. In an ongoing population-based birth
      cohort study of 562 children, follow-up visits were performed at 0, 3, 6, 9, 12,
      18, 36, and 72 months. Visits included an interview, physical examination, SPTs,
      and S-IgE measurements for 12 food and inhalant allergens. The frequency of S-IgE
      sensitization to > or = 1 inhalant allergen was constant from 0 to 6 months (9
      10%), decreased at 12-18 months before increasing from 36 months onwards. S-IgE
      sensitization to at least one food allergen remained constant from 0 to 6 yr. SPT
      sensitization to food and inhalant allergens appeared from 3 and 12 months,
      respectively. Early food sensitization (S-IgE) between 3 and 18 months was found
      to be significantly (p < 0.05) associated with atopic dermatitis (OR: 4.0 [1.6
      9.9]) and asthma (OR 4.0 [1.1-12.5]) at the age of 6 yr. Children with atopic
      dermatitis, asthma, or rhinoconjunctivitis, and sensitization at 6 yr, were
      sensitized to food allergens to a large extent (53%, 42%, and 47%, respectively)
      already at 6 months. Early inhalant sensitization (S-IgE) did not increase the
      risk of later allergic disease. Early atopic dermatitis (0-18 months) was also
      highly associated with subsequent allergic disease. Children with early food
      sensitization and/or atopic dermatitis would be a proper target group for future
      interventional studies.

PMID- 19744223
TI  - Randomized trial of cyclosporine and tacrolimus therapy with steroid withdrawal
      in living-donor renal transplantation: 5-year follow-up.
AB  - SUMMARY: The aim of this study was to compare the long-term safety and efficacy
      of immunosuppressive regimens consisting of cyclosporine (CsA) plus mycophenolate
      mofetil (MMF) or tacrolimus (TAC) plus MMF after steroid withdrawal 6 months
      after kidney transplantation in low-risk patients. One hundred and thirty-one
      patients were randomized to receive either CsA (n = 63) or TAC (n = 68). Of
      these, 117 patients satisfied the criteria for steroid withdrawal (no biopsy
      proven rejection episode and serum creatinine level <2.0 mg/dl 6 months after
      transplantation). Fifty-five recipients were of the CsA group, and 62 were of the
      TAC group. The 5-year graft survival rate did not differ between groups (90.5%
      vs. 93.3% respectively; P = 0.55). The cumulative incidence of acute rejection 5
      years after transplantation was 16.4% and 8.1% for the CsA and TAC groups
      respectively (P = 0.15). Post-transplantation diabetes mellitus was more frequent
      in the TAC group than in the CsA group (P = 0.05), but the incidence of other
      side-effects did not differ between groups. In conclusion, CsA- and TAC-based
      regimens in conjunction with MMF have similar patient- and graft survival rates
      in low-risk patients who underwent steroid withdrawal 6 months after kidney
      transplantation.

PMID- 19744224
TI  - Dosing information in a standard drug reference: are pediatrics still
      therapeutically neglected?
AB  - BACKGROUND: In many countries, the most readily accessible drug information
      resources, such as the Monthly Index of Medical Specialties (MIMS), lack
      information concerning use in children. We reviewed the product information (PI)
      of medications in the most widely used drug information reference in Malaysia in
      an effort to determine the extent and the nature of available information related
      to pediatric dosing. METHODS: The products listed in the 2007 Malaysian MIMS
      Annual were reviewed for PI on pediatric use as per inclusion and exclusion
      criteria. The dosing information for each PI was extracted according to age
      groups. Product information that claimed suitability for use in pediatrics was
      further evaluated for information on pediatric dosage formulations. RESULTS: A
      total of 421 PI items from seven categories of therapeutic classes were reviewed.
      Of these, 69% gave inadequate pediatric dosing information. The proportions, for
      each age group of PI items that gave adequate pediatric dosing information were:
      neonates (13.1%), infants (23.3%), and children (32.2%). Therapeutic classes of
      drugs differed significantly in terms of dosing information adequacy for all
      pediatric age groups (P < 0.05). Most PI reviewed under all legal categories
      provided inadequate pediatric dosing information, but suitable pediatric
      formulations were commonly (70.1-85.5%) available where the dosing information
      existed. Overall, category B (prescription only) products did not differ
      significantly from category C (pharmacy only medicine) products in terms of
      pediatric dosing information adequacy, except for children. CONCLUSION: This
      study has managed to contribute substantial additional information regarding the
      extent of pediatric dosing information and dosage formulations available in the
      MIMS Annual, stressing that the majority of PI for the products reviewed did not
      provide adequate dosing information for pediatric patients, subjecting this
      population to a therapeutically disadvantaged status.

PMID- 19744225
TI  - Passive smoking is associated with lower serum HDL-C levels in school children.
AB  - BACKGROUND: In recent years, a number of studies have reported that exposure to
      environmental tobacco smoke (ETS) reduces high-density lipoprotein cholesterol
      (HDL-C) levels in children, as well as in adults. Further, a number of countries
      have indicated that passive smoking increases the risk of early arteriosclerosis
      onset. Here, to evaluate the effects of ETS exposure, we conducted a cross
      sectional epidemiological study on primary school children in Japan using answers
      from a questionnaire survey, as well as urine cotinine and lipid metabolism
      related variable measurements. METHODS: A total of 121 sixth-grade primary school
      children participated in this study by completing a questionnaire about their
      food intake, lifestyle and family smoking habits. Early in the morning, we also
      measured height, weight, blood pressure, serum levels of total cholesterol,
      triglyceride, HDL-C, and blood sugar, as well as urine levels of cotinine and
      creatinine under unfed conditions. RESULTS: From the questionnaire, 40 and 81
      children reported being exposed and not exposed to ETS, respectively. Serum HDL-C
      levels, which were adjusted for the degree of corpulence and exercise habits,
      were significantly lower in the passive smoker group than the non-passive-smoker
      group (65.3 and 72.1 mg/dL, respectively; P= 0.012). In addition, proportional
      differences in serum HDL-C levels were also observed based on the amount of
      cigarettes smoked at home by family members of the child. CONCLUSIONS: Results
      suggest that ETS exposure at home is associated in a dose-related manner with
      lower serum HDL-C levels in primary school children. In addition, our results
      suggest that smoking in the presence of children who are not usually exposed to
      ETS increases the risk of arteriosclerosis. Given these findings, we strongly
      recommend the establishment of anti-passive-smoking measures.

PMID- 19744226
TI  - Evaluation of angiogenesis with vascular endothelial growth factor in patients
      with thalassemia major.
AB  - BACKGROUND: Thalassemia major (TM) is an important cause of severe anemia that
      necessitates regular blood transfusion to prevent the profound weakness and
      cardiac decompensation caused by the anemia. However, iron overloading is an
      inevitable consequence of prolonged transfusion therapy. In addition,
      extramedullary hematopoiesis and hemosiderosis cause spleen, liver and marrow
      enlargement. In recent years the role of angiogenesis has been investigated in
      physiological and pathological conditions. However, it is known that angiogenetic
      factors, especially the vascular endothelial growth factor (VEGF), cause
      differentiation of the hemangioblast. METHODS: The effect of angiogenesis hasn't
      been investigated in TM patients yet, and in this study, angiogenesis was
      researched in 43 thalassemic patients by serum VEGF measurement. RESULTS: VEGF
      levels were not affected by hemoglobin levels, ferritin levels, or chelation type
      (P > 0.05). However, VEGF was positively affected by chelation starting age and
      negatively affected by yearly transfusion requirement of TM patients (P < 0.05).
      In addition, VEGF of patients who underwent splenectomy were higher than those
      who didn't undergo splenectomy (P < 0.05). CONCLUSION: Early chelating age will
      negatively influence the VEGF level, which increases angiogenesis, however, early
      starting transfusion age and regular blood transfusion will positively influence
      the VEGF level, which decreases angiogenesis in thalassemic patients.

PMID- 19744227
TI  - Symptomless celiac disease in type 1 diabetes: 12-year experience in Estonia.
AB  - BACKGROUND: We aimed to determine the prevalence and characteristics of celiac
      disease in children with type 1 diabetes in Estonia, a country with a formerly
      low frequency of both diseases. METHODS: Altogether, 271 patients with diabetes
      were studied over 12 years (1995-2006): 122 at diagnosis and 149 patients 0.1
      14.8 years after diagnosis. In addition, 73 patients were followed up over 1-6
      years. Immunoglobulin A type endomysium and tissue transglutaminase antibodies
      were determined. Patients with antibodies and/or with celiac-disease-related
      symptoms were invited for a small-intestinal biopsy. RESULTS: At the primary
      screening, celiac disease was histologically confirmed in nine patients (all
      without symptoms), that is, in 3.3% (95% confidence interval: 1.63-6.42) of type
      1 diabetes cases. At follow up, celiac disease was additionally detected in two
      (2.7%) of 73 diabetic patients, that is, in 0.016 (95% confidence interval: 0
      0.072) celiac disease cases per follow-up year. CONCLUSION: The prevalence of
      celiac disease among type 1 diabetes patients in Estonia is similar to that in
      countries with a high incidence of celiac disease and type 1 diabetes. As celiac
      disease is mostly symptomless, all children with type 1 diabetes, irrespective of
      their geographic origin, should be regularly screened for celiac disease.

PMID- 19744228
TI  - Soluble tumor necrosis factor receptor-1 in preterm infants with chronic lung
      disease.
AB  - BACKGROUND: It is clear that inflammation plays an important role in developing
      chronic lung disease in preterm infants. The purpose of the present study is to
      investigate changes of serum soluble tumor necrosis factor receptor-1 levels over
      time in infants with chronic lung disease. METHODS: The serum levels of soluble
      tumor necrosis factor receptor-1 were measured after delivery, and at 7, 14, 21
      and 28 days of age in 10 infants with chronic lung disease and in 18 infants
      without chronic lung disease. RESULTS: The serum level of soluble tumor necrosis
      factor receptor-1 was significantly higher in infants with chronic lung disease
      than in infants without chronic lung disease after delivery. The differences
      between these two groups remained up to 28 days of age. CONCLUSION: Prenatal
      inflammation with persistence into postnatal inflammation may be involved in the
      onset of chronic lung disease.

PMID- 19744229
TI  - A novel missense mutation in the EVC gene underlies Ellis-van Creveld syndrome in
      a Pakistani family.
AB  - BACKGROUND: Ellis-van Creveld (EVC) syndrome is a rare autosomal recessive
      disorder characterized by skeletal, ectodermal and cardiac defects. This syndrome
      is caused by mutations in EVC and EVC2 genes, which are separated by 2.6 kb of
      genomic sequence on chromosome 4p16. METHODS: In the present study we ascertained
      a four-generation pedigree of Pakistani origin with features of EVC. Linkage was
      searched by genotyping microsatellite markers linked to chromosome 4p16. Affected
      individuals showed homozygosity to the microsatellite markers tightly linked to
      EVC and EVC2 genes on chromosome 4p16. It was then subjected to direct sequencing
      of the EVC and EVC2 genes. RESULTS: Mutation analysis of the EVC and EVC2 genes
      identified a novel missense change (c.617G>A; p.S206N) in the EVC gene.
      CONCLUSIONS: We herein report on the first family from Pakistan with a large
      number of individuals affected by EVC. DNA sequence analysis led to the
      identification of the fifth missense mutation in the EVC gene.

PMID- 19744230
TI  - Imipenem-cilastatin versus piperacillin-tazobactam as monotherapy in febrile
      neutropenia.
AB  - BACKGROUND: In view of the recent trend toward monotherapy in the treatment of
      febrile neutropenia, we evaluated the clinical efficacy and safety of imipenem
      cilastatin versus piperacillin-tazobactam as an empiric therapy for febrile
      neutropenia in children with malignant diseases. METHODS: Febrile neutropenic
      patients received either imipenem-cilastatin or piperacillin-tazobactam randomly.
      Improvement without any changes in the initial antibiotic treatment was defined
      as "success" and improvement with modification of the initial treatment and death
      was defined as "failure". RESULTS: Over 12 months, 99 febrile neutropenic
      episodes were treated with monotherapy in 63 patients with a median age of 5
      years. At admission, median absolute neutrophil count was 50/mm(3) and in 67% of
      episodes, neutrophil count was under 100/mm(3). Median duration of neutropenia
      was 5 days. In 22% of episodes, neutropenia persisted for more than 10 days.
      Piperacillin-tazobactam was used in 52 episodes and imipenem-cilastatin was used
      in 47 episodes. There was no difference between groups in terms of age, sex,
      primary diseases, neutrophil count or duration of neutropenia. In the whole
      group, the success rate was 67% and the failure rate was 33%, whereas in the
      piperacillin-tazobactam group, the rates were 71% and 29%; and in the imipenem
      cilastatin group they were 62% and 38%, respectively (P > 0.05). There were no
      deaths. No major adverse effects were seen in either group. CONCLUSIONS: Although
      failure was slightly higher in the imipenem-cilastatin group, this was
      statistically insignificant. Both of these antibiotics can be used safely for
      initial empirical monotherapy of febrile neutropenia.

PMID- 19744231
TI  - Physical activity, fitness and fatness: relations to mortality, morbidity and
      disease risk factors. A systematic review.
AB  - The purpose of this systematic review was to study the relative health risks of
      poor cardio-respiratory fitness (or physical inactivity) in normal-weight people
      vs. obesity in individuals with good cardio-respiratory fitness (or high physical
      activity). The core inclusion criteria were: publication year 1990 or later;
      adult participants; design prospective follow-up, case-control or cross
      sectional; data on cardio-respiratory fitness and/or physical activity; data on
      BMI (body mass index), waist circumference or body composition; outcome data on
      all-cause mortality, cardiovascular disease mortality, cardiovascular disease
      incidence, type 2 diabetes or cardiovascular and type 2 diabetes risk factors.
      Thirty-six publications filled the criteria for inclusion. The data indicate that
      the risk for all-cause and cardiovascular mortality was lower in individuals with
      high BMI and good aerobic fitness, compared with individuals with normal BMI and
      poor fitness. In contrast, having high BMI even with high physical activity was a
      greater risk for the incidence of type 2 diabetes and the prevalence of
      cardiovascular and diabetes risk factors, compared with normal BMI with low
      physical activity. The conclusions of the present review may not be applicable to
      individuals with BMI > 35.

PMID- 19744233
TI  - Equine encephalosis virus in Israel.

PMID- 19744234
TI  - Investigations into the cause of foot-and-mouth disease virus seropositive small
      ruminants in Cyprus during 2007.
AB  - In 2007, serological evidence for foot-and-mouth disease (FMD) infection was
      found as a result of differential diagnostic testing of Cypriot sheep suspected
      to be infected with bluetongue or contagious ecthyma. Seropositive sheep and
      goats were subsequently uncovered on ten geographically clustered flocks, while
      cattle and pigs in neighbouring herds were all seronegative. These antibodies
      were specific for serotype-O FMD virus, reacting with both structural and non
      structural (NS) FMD viral proteins. However, no FMD virus could be recovered from
      the seropositive flocks. FMD had not been recorded in Cyprus since 1964 and there
      has been no vaccination programme since 1984. Since all the seropositive animals
      were at least 3 years old and home-bred, it was concluded that infection had
      occurred approximately 3 years previously had passed un-noticed and died out
      spontaneously. It therefore appears that antibodies to FMD virus NS proteins can
      still be detected around 3 years after infection of small ruminants, but that
      virus carriers cannot be detected at this time. This unusual situation of finding
      evidence of historical infection in a FMD-free country caused considerable
      disruption and alarm and posed questions about the definition of what constitutes
      a FMD outbreak.

PMID- 19744235
TI  - Sequence analysis of the S10 gene of six Bluetongue Virus isolates from India.
AB  - Bluetongue Virus (BTV) genome segment 10 (S10)-based phylogenetic studies are
      important in understanding the BTV evolution. S10 gene-based phylogenetic
      analysis grouped six different BTV isolates (BTV serotype 1, 18 and 23) from
      India in subclade A1 and showed closer relationship with BT viruses from
      Mediterranean Basin. Indian BTV serotypes 18 and 23 formed a single cluster
      distinct from BTV serotype 1 isolates and were evolved from BTV from China,
      Indonesia and Australia. The overall S10 sequences of BTV isolates from India
      were largely conserved (>95.7% homology) and were distinct from other BT viruses
      of the world.

PMID- 19744236
TI  - Effect of carbon addition and predation on acetate-assimilating bacterial cells
      in groundwater.
AB  - Groundwater microbial community dynamics are poorly understood due to the
      challenges associated with accessing subsurface environments. In particular,
      microbial interactions and their impact on the subsurface carbon cycle remain
      unclear. In the present project, stable isotope probing with uniformly labeled
      [(13)C]-acetate was used to identify metabolically active and inactive bacterial
      populations based on their ability to assimilate acetate and/or its metabolites.
      Furthermore, we assessed whether substrate availability (bottom-up control) or
      grazing mortality (top-down control) played a greater role in shaping bacterial
      community composition by separately manipulating the organic carbon supply and
      the protozoan grazer population. A community fingerprinting technique, terminal
      restriction fragment length polymorphism, revealed that the bacterial community
      was not affected by changes in acetate availability but was significantly altered
      by the removal of protozoan grazers. In silico identification of terminal
      restriction fragments and 16S rRNA gene sequences from clone libraries revealed a
      bacterial community dominated by Proteobacteria, Firmicutes, and Bacteroidetes.
      Elucidation of the factors that structure the bacterial community will improve
      our understanding of the bacterial role in the carbon cycle of this important
      subterranean environment.

PMID- 19744237
TI  - Anaerobic oxidation of dimethylsulfide and methanethiol in mangrove sediments is
      dominated by sulfate-reducing bacteria.
AB  - The oxidation of dimethylsulfide and methanethiol by sulfate-reducing bacteria
      (SRB) was investigated in Tanzanian mangrove sediments. The rate of
      dimethylsulfide and methanethiol accumulation in nonamended sediment slurry
      (control) incubations was very low while in the presence of the inhibitors
      tungstate and bromoethanesulfonic acid (BES), the accumulation rates ranged from
      0.02-0.34 to 0.2-0.4 nmol g FW sediment(-1) h(-1), respectively. Degradation
      rates of methanethiol and dimethylsulfide added were 2-10-fold higher. These
      results point to a balance of production and degradation. Degradation was
      inhibited much stronger by tungstate than by BES, which implied that SRB were
      more important. In addition, a new species of SRB, designated strain SD1, was
      isolated. The isolate was a short rod able to utilize a narrow range of
      substrates including dimethylsulfide, methanethiol, pyruvate and butyrate. Strain
      SD1 oxidized dimethylsulfide and methanethiol to carbon dioxide and hydrogen
      sulfide with sulfate as the electron acceptor and exhibited a low specific growth
      rate of 0.010 +/- 0.002 h(-1), but a high affinity for its substrates. The
      isolated microorganism could be placed in the genus Desulfosarcina (the most
      closely related cultured species was Desulfosarcina variabilis, 97% identity).
      Strain SD1 represents a member of the dimethylsulfide/methanethiol-consuming SRB
      population in mangrove sediments.

PMID- 19744238
TI  - Conjugal transfer and mobilization capacity of the completely sequenced
      naphthalene plasmid pNAH20 from multiplasmid strain Pseudomonas fluorescens PC20.
AB  - The complete 83 042-bp nucleotide sequence of the IncP-9 naphthalene degradation
      plasmid pNAH20 from Pseudomonas fluorescens PC20 exhibits striking similarity in
      size and sequence to another naphthalene (NAH) plasmid pDTG1. However, the
      positions of insertion sequence (IS) elements significantly alter both catabolic
      and backbone functions provided by the two plasmids. In pDTG1, insertion of a
      pCAR1 ISPre1-like element disrupts expression of the lower naphthalene operon and
      this strain utilizes the chromosomal pathway for complete naphthalene
      degradation. In pNAH20, this operon is intact and functional. The transfer
      frequency of pNAH20 is 100 times higher than that of pDTG1 probably due to
      insertion of the pCAR1 ISPre2-like element into the mpfR gene coding for a
      putative repressor of the mpf operon responsible for mating pilus formation. We
      also demonstrate in situ plasmid transfer - we isolated a rhizosphere
      transconjugant strain of pNAH20, P. fluorescens NS8. The plasmid pNS8, a
      derivative of pNAH20, lacks the ability to self-transfer as a result of an
      additional insertion event of ISPre2-like element that disrupts the gene coding
      for VirB2-like major pilus protein MpfA. The characteristics of the strain PC20
      and the conjugal transfer/mobilization capacity of pNAH20 (or its backbone) make
      this strain/plasmid a potentially successful tool for bioremediation
      applications.

PMID- 19744239
TI  - Extracellular release of a heterologous phytase from roots of transgenic plants:
      does manipulation of rhizosphere biochemistry impact microbial community
      structure?
AB  - To maintain the sustainability of agriculture, it is imperative that the reliance
      of crops on inorganic phosphorus (P) fertilizers is reduced. One approach is to
      improve the ability of crop plants to acquire P from organic sources. Transgenic
      plants that produce microbial phytases have been suggested as a possible means to
      achieve this goal. However, neither the impact of heterologous expression of
      phytase on the ecology of microorganisms in the rhizosphere nor the impact of
      rhizosphere microorganisms on the efficacy of phytases in the rhizosphere of
      transgenic plants has been tested. In this paper, we demonstrate that the
      presence of rhizosphere microorganisms reduced the dependence of plants on
      extracellular secretion of phytase from roots when grown in a P-deficient soil.
      Despite this, the expression of phytase in transgenic plants had little or no
      impact on the microbial community structure as compared with control plant lines,
      whereas soil treatments, such as the addition of inorganic P, had large effects.
      The results demonstrate that soil microorganisms are explicitly involved in the
      availability of P to plants and that the microbial community in the rhizosphere
      appears to be resistant to the impacts of single-gene changes in plants designed
      to alter rhizosphere biochemistry and nutrient cycling.

PMID- 19744240
TI  - The vertical distribution of bacterial and archaeal communities in the water and
      sediment of Lake Taihu.
AB  - This study was conducted to characterize the vertical distribution of bacterial
      and archaeal communities in the water and sediment of Lake Taihu, which underwent
      a change in trophic status from oligotrophic to hypertrophic in last half of the
      20th century. The results revealed that the bacterial communities in different
      layers of sediment sample were very similar, and were related to Alpha-, Beta-,
      Gamma- and Deltaproteobacteria, Nitrospira, Bacteroidetes, Firmicutes,
      Gemmatimonadetes, Verrucomicrobia, Chlorobi, Actinobacteria and Acidobacteria. In
      contrast, the archaeal communities varied greatly with depth. The archaeal
      communities were primarily related to Euryarchaeota and Crenarchaeota, with
      methanogenic Archaea accounting for approximately 2-35% of the total Archaea.
      Additionally, sequences related to putative ammonia-oxidizing Archaea and ammonia
      oxidizing Bacteria were detected in different layers of sediment samples. The
      abundance of Archaea, Bacteria, methanogenic Archaea and Nitrospira was further
      characterized by real-time PCR.

PMID- 19744241
TI  - Vertical distribution and diversity of sulfate-reducing prokaryotes in the Pearl
      River estuarine sediments, Southern China.
AB  - The vertical distribution and diversity of sulfate-reducing prokaryotes (SRPs) in
      a sediment core from the Pearl River Estuary was reported for the first time. The
      profiles of methane and sulfate concentrations along the sediment core indicated
      processes of methane production/oxidation and sulfate reduction. Phospholipid
      fatty acids analysis suggested that sulfur-oxidizing bacteria (SOB) might be
      abundant in the upper layers, while SRPs might be distributed throughout the
      sediment core. Quantitative competitive-PCR analysis indicated that the ratios of
      SRPs to total bacteria in the sediment core varied from around 2-20%. Four
      dissimilatory sulfite reductase (dsrAB) gene libraries were constructed and
      analyzed for the top layer (0-6 cm), middle layer (18-24 cm), bottom layer (44-50
      cm) and the sulfate-methane transition zone (32-42 cm) sediments. Most of the
      retrieved dsrAB sequences (80.9%) had low sequence similarity with known SRP
      sequences and formed deeply branching dsrAB lineages. Meanwhile, bacterial 16S
      rRNA gene analysis revealed that members of the Proteobacteria were predominant
      in these sediments. Putative SRPs within Desulfobacteriaceae, Syntrophaceae and
      Desulfobulbaceae of Deltaproteobacteria, and putative SOB within
      Epsilonproteobacteria were detected by the 16S rRNA gene analysis. Results of
      this study suggested a variety of novel SRPs in the Pearl River Estuary
      sediments.

PMID- 19744242
TI  - Presence of T3SS2 and other virulence-related genes in tdh-negative Vibrio
      parahaemolyticus environmental strains isolated from marine samples in the area
      of the Venetian Lagoon, Italy.
AB  - Vibrio parahaemolyticus-mediated disease has traditionally been associated with
      two virulence factors, thermostable direct haemolysin (TDH) and TDH-related
      haemolysin (TRH), which are present in most clinical isolates. Recently, it has
      been suggested that other virulence-related factors, such as some type III
      secretion system (T3SS) proteins, urease and DNA-methyltransferase, among others,
      might also play a role in disease caused by this bacterial species and have been
      shown to be carried by clinical, but not by environmental strains. Screening for
      a number of virulence and virulence-related genes in a collection of V.
      parahaemolyticus strains isolated from the Italian Adriatic coast indicates that
      in addition to the trh-positive strains isolated (6%), a significant percentage
      (18%) of these strains contain one or more genes with a possible role in
      pathogenicity. Specifically, some of the V. parahaemolyticus strains described in
      this study are the first environmental strains ever detected carrying T3SS2
      genes. Data obtained by reverse transcription-PCR on environmental strain RNA
      indicate that at least some of these genes are functional. On the basis of the
      results obtained, it is suggested that such strains might constitute an
      environmental reservoir of genes possibly contributing to V. parahaemolyticus
      pathogenicity and to the spread, in the marine environment, of virulence-related
      genes usually found in clinical strains.

PMID- 19744243
TI  - A novel inorganic pyrophosphatase in Thermococcus onnurineus NA1.
AB  - The TON_0002 gene, which is in close proximity to the DNA polymerase locus in
      Thermococcus onnurineus NA1, has been shown to encode an inorganic
      pyrophosphatase. Its genomic position and function suggest a role for
      pyrophosphate hydrolysis during DNA polymerization. This is the first report of
      an inorganic pyrophosphatase belonging to the haloacid dehalogenase superfamily,
      in which unique residues in motif I and II have been replaced with Trp and Gly,
      respectively. The optimum pyrophosphatase activity of the recombinant enzyme
      occurred at pH 6, and it displayed an absolute dependence on divalent metal ions,
      among which Ni(2+) was the most efficient. The site-specific mutation of the Gly
      residue in motif II to Ala or Ser residue exhibited only a slight change in the
      enzymatic activity and the K(m) value.

PMID- 19744244
TI  - Free-living amoebae and their intracellular pathogenic microorganisms: risks for
      water quality.
AB  - An increasing number of microorganisms, including bacteria but also viruses and
      eukaryotes, have been described as benefiting from interaction with free-living
      amoebae (FLA). Beneficial interaction can be due to resistance to predation
      conferring ecological advantage, intracellular survival and/or intracellular
      proliferation. This review highlights the potential risk associated with amoebae
      by listing all known pathogenic microbial species for which growth and/or
      survival promotion by FLA (mainly Acanthamoeba spp.) has been demonstrated. It
      focuses on the susceptibility of amoebal and intra-amoebal bacteria to various
      categories of biocides, the known mechanisms of action of these biocides against
      trophozoites and cysts and the various methods used to demonstrate efficacy of
      treatments against FLA. Brief descriptions of FLA ecology and prevalence in
      domestic/institutional water systems and their intrinsic pathogenicity are also
      presented. The intention is to provide an informed opinion on the environmental
      risks associated with the presence of FLA and on the survival of cysts following
      biocidal treatments, while also highlighting the need to conduct research on the
      roles of amoebae in aquatic ecosystems.

PMID- 19744245
TI  - Heterologous expression of a Clostridium minicellulosome in Saccharomyces
      cerevisiae.
AB  - The yeast Saccharomyces cerevisiae was genetically modified to assemble a
      minicellulosome on its cell surface by heterologous expression of a chimeric
      scaffoldin protein from Clostridium cellulolyticum under the regulation of the
      phosphoglycerate kinase 1 (PGK1) promoter and terminator regulatory elements,
      together with the beta-xylanase 2 secretion signal of Trichoderma reesei and cell
      wall protein 2 (Cwp2) of S. cerevisiae. Fluorescent microscopy and Far Western
      blot analysis confirmed that the Scaf3p is targeted to the yeast cell surface and
      that the Clostridium thermocellum cohesin domain is functional in yeast.
      Similarly, functionality of the C. thermocellum dockerin domain in yeast is shown
      by binding to the Scaf3 protein in Far Western blot analysis. Phenotypic evidence
      for cohesin-dockerin interaction was also established with the detection of a
      twofold increase in tethered endoglucanase enzyme activity in S. cerevisiae cells
      expressing the Scaf3 protein compared with the parent strain. This study
      highlights the feasibility to future design of enhanced cellulolytic strains of
      S. cerevisiae through emulation of the cellulosome concept. Potentially, Scaf3p
      armed yeast could also be developed into an alternative cell surface display
      strategy with various tailor-made applications.

PMID- 19744246
TI  - Why does Candida albicans switch?
AB  - White-opaque switching in Candida albicans was first discovered in 1987. Fifteen
      years later, and three years after the discovery of the mating system, it was
      demonstrated that the switch from white to opaque was an essential step in the
      mating process. But this latter discovery did not reveal why C. albicans had this
      requirement, when Saccharomyces cerevisiae and other hemiascomycetes did not. The
      discovery that mating-competent opaque cells signaled mating-incompetent white
      cells, through the release of pheromones, to become adhesive and form biofilms
      provided a clue to this fundamental question. Opaque cells appeared to signal
      white cells to form biofilms that facilitated mating by protecting the fragile
      gradients of the pheromone that directed chemotropism, a process necessary for
      fusion. Here, we explore the discoveries and observations that have led to this
      hypothesis, and the ancillary questions that have risen that are related to the
      regulation of the unique pheromone response, the evolution of this response and
      the relationship between pheromone-enhanced white cell biofilms and 'asexual'
      biofilms formed by a/alpha cells. This discussion, therefore, focuses on a unique
      and complex component of the basic biology of C. albicans that relates switching,
      mating and pathogenesis.

PMID- 19744247
TI  - The isoprenoid pathway and transcriptional response to its inhibitors in the
      yeast Saccharomyces cerevisiae.
AB  - This review presents new insights into the regulation of the isoprenoid pathway
      in the yeast Saccharomyces cerevisiae, in particular the short-term
      transcriptional response to two inhibitors, lovastatin and zaragozic acid (ZA).
      Whereas lovastatin blocks whole isoprenoid pathway, ZA only blocks the sterol
      branch. Consequently, their effects on the cellular level of farnesyl diphosphate
      (FPP) are different. Lovastatin decreases the FPP level, whereas ZA, by
      inhibiting the main FPP-consuming enzyme, increases FPP availability in the cell.
      We discuss the role of genes whose expression is affected by both inhibitors and
      consider possible association of these genes with the regulation of the
      isoprenoid pathway.

PMID- 19744248
TI  - CHICAGO, PERISCOPE and PROactive: CV risk modification in diabetes with
      pioglitazone.
AB  - Recent trials of intensive glycaemic control in patients with type 2 diabetes and
      its impact on cardiovascular disease have led to confusion and speculation
      amongst physicians. The Action to Control Cardiovascular Risk in Diabetes Study
      was terminated early because of a significant excess all-cause mortality in the
      intensively-treated group. Furthermore the ADVANCE and VADT trials did not
      demonstrate cardiovascular benefit with more intensive glycaemic control. Against
      this background, it is pertinent to re-visit and critically appraise the results
      of the PROactive study which examined the effects of the thiazolidinedione,
      pioglitazone, on cardiovascular end-points in a large, randomized, placebo
      controlled clinical trial in type 2 diabetic patients with symptomatic disease.
      PROactive has been rightly criticized in the choice of its composite primary end
      point which included a physician-driven as opposed to a disease-driven outcome,
      namely peripheral vascular re-vascularization. This was primarily responsible for
      the primary composite end-point not being achieved; whereas there was a
      significant beneficial impact on the major secondary end-point of death, non
      fatal myocardial infarction and stroke. The results of PROactive have been
      supported by two subsequent studies examining the impact of pioglitazone on
      important surrogates of atherosclerosis, namely carotid intima/medial thickness
      (IMT) and coronary atheroma volume as delineated with intravascular ultrasound.
      The CHICAGO study demonstrated that IMT in type 2 diabetic patients treated with
      pioglitazone did not progress whereas those treated with glimepiride showed
      progression. In PERISCOPE atheroma volume progressed with glimepiride but did not
      with pioglitazone. This is exciting data pointing to the cardiovascular benefits
      of pioglitazone. In PROactive, CHICAGO and PERISCOPE there was a sustained effect
      of pioglitazone on glycaemic control and, in addition, beneficial effects in
      reducing triglycerides and increasing HDL-cholesterol beyond that seen with
      concomitant statin therapy. These findings strongly suggest that pioglitazone has
      an important place in the management of type 2 diabetes.

PMID- 19744249
TI  - Practical postcalibration uncertainty analysis: Yucca Mountain, Nevada.
AB  - The values of parameters in a groundwater flow model govern the precision of
      predictions of future system behavior. Predictive precision, thus, typically
      depends on an ability to infer values of system properties from historical
      measurements through calibration. When such data are scarce, or when their
      information content with respect to parameters that are most relevant to
      predictions of interest is weak, predictive uncertainty may be high, even if the
      model is "calibrated." Recent advances help recognize this condition,
      quantitatively evaluate predictive uncertainty, and suggest a path toward
      improved predictive accuracy by identifying sources of predictive uncertainty and
      by determining what observations will most effectively reduce this uncertainty.
      We demonstrate linear and nonlinear predictive error/uncertainty analyses as
      applied to a groundwater flow model of Yucca Mountain, Nevada, the United States'
      proposed site for disposal of high-level radioactive waste. Linear and nonlinear
      uncertainty analyses are readily implemented as an adjunct to model calibration
      with medium to high parameterization density. Linear analysis yields
      contributions made by each parameter to a prediction's uncertainty and the worth
      of different observations, both existing and yet-to-be-gathered, toward reducing
      this uncertainty. Nonlinear analysis provides more accurate characterization of
      the uncertainty of model predictions while yielding their (approximate)
      probability distribution functions. This article applies the above methods to a
      prediction of specific discharge and confirms the uncertainty bounds on specific
      discharge supplied in the Yucca Mountain Project License Application.

PMID- 19744250
TI  - Institutional challenges for national groundwater governance: policies and
      issues.
AB  - Understanding the issues surrounding groundwater governance is a precondition for
      developing policy recommendations for both national and transboundary groundwater
      governance. This review discusses groundwater attributes relevant to the design
      of governance systems and provides a systematic review of current national
      groundwater governance differentiated by various policy instruments. The
      synthesis of both resource system characteristics and experience with policy
      instruments allows us to conceptualize institutional aspects of groundwater
      governance. This leads to six institutional aspects: (1) voluntary compliance;
      (2) tradition and mental models; (3) administrative responsibility and
      bureaucratic inertia; (4) conflict resolution mechanisms; (5) political economy;
      and (6) information deficits. Each of these issues embodies institutional
      challenges for national and international policy implementation.

PMID- 19744251
TI  - Assessment of the progression of haemophilic arthropathy in children.
AB  - Arthropathy is considered as an irreversible and progressive complication in
      patients with haemophilia, even in children on prophylaxis. To estimate the
      progression of haemophilic arthropathy, 85 joints of 24 boys with severe (n = 18)
      and moderate (n = 6) haemophilia (A: 22, B: 2) were investigated with clinical
      examination, X-rays and magnetic resonance imaging (MRI) at two time periods
      (time 0 and 1). Patients' age at time 0 was 10.5 +/- 3.6 years and time elapsed
      to time 1 was 3.8 +/- 1.4 years. At time 0: all investigated joints had more than
      three bleeds. Sixteen boys were on secondary prophylaxis for 5.4 +/- 2.8 years.
      Clinical score (a modification of World Federation of Haemophilia's scale): 2.0
      +/- 3.6, X-ray score (Pettersson): 2.1 +/- 2.8, MRI score (Denver): 4.5 +/- 3.8.
      After the first evaluation, prophylaxis was intensified in 11 children and
      initiated in four. At time 1: clinical score: 1.5 +/- 3.1, X-ray: 1.7 +/- 2.7,
      MRI score: 5.1 +/- 4.1. On average, the clinical and X-ray scores showed a
      significant improvement (26% and 40% of the joints respectively, P < 0.01) and
      the number of haemarthroses evidenced a threefold reduction from time 0 to 1 (P <
      0.01), findings that could be associated with the modification of prophylaxis
      after time 0. MRI findings showed deterioration in 34% of the joints. Conversely,
      14 joints (16.5%) with mild or moderate synovitis without cartilage degradation
      at time 0 showed an improvement at time 1. The information carried by the three
      scales could be divided into information shared by the three scores and
      information specific to each score, thus giving a more complete picture of joint
      damage caused by bleedings.

PMID- 19744252
TI  - Measurement-specific bioavailable testosterone using concanavalin A
      precipitation: comparison of calculated and assayed bioavailable testosterone.
AB  - OBJECTIVE: To assess the value of calculated bioavailable testosterone (cBT) and
      assayed BT (aBT) for the diagnosis of late-onset hypogonadism (LOH) in middle
      aged and elderly subjects. METHODS: In order to assay serum BT, sex hormone
      binding globulin was precipitated with concanavalin-A and then testosterone was
      measured using liquid chromatography-tandem mass spectrometry. To validate the
      non-sex-hormone-binding-globulin-bound testosterone, gel filtration
      chromatography and concanavalin-A sepharose were used. Following this validation,
      the usefulness between aBT and cBT was evaluated in clinical samples. RESULTS:
      Eighty-eight healthy male volunteers (mean age 65.6 years, range: 50-86) were
      recruited for this study. A significant correlation was found between cBT and aBT
      (R(2) = 0.53, P < 0.01). Mean value ratio (cBT/aBT) was 2.48. Both cBT (R(2) =
      0.122) and aBT (R(2) = 0.251) decreased with age. Variations in aBT were less
      marked than those for cBT, suggesting that aBT can be used to determine age
      related reduced testosterone levels. CONCLUSION: aBT levels are more reliable
      than cBT levels for the diagnosis of LOH in middle-aged and elderly subjects.

PMID- 19744253
TI  - Negotiation of parental care when the stakes are high: experimental handicapping
      of one partner during incubation leads to short-term generosity.
AB  - 1. Most game theoretical models of biparental care predict that a reduction in
      care by one partner should not be fully compensated by increased work of its mate
      but this may not be true for incubating birds because a reduction in care could
      cause the entire brood to fail. 2. I performed the first handicapping experiment
      of both males and females during incubation, by placing small lead weights on the
      tails of male and female northern flickers Colaptes auratus, a woodpecker in
      which males do most of the incubation. 3. Females responded to the acute stressor
      (handling and handicapping) by tending to abandon more readily than males and
      staying away from the nest longer in the first incubation bout. Among pairs that
      persisted, both males and females compensated fully for a handicapped partner,
      keeping the eggs covered nearly 100% of the time. 4. Partners did not retaliate
      by forcing their handicapped mate to sit on the eggs with a long incubation bout
      length subsequent to having a long bout length themselves. Instead, during the 24
      h immediately after handicapping, males behaved generously by relieving
      handicapped females early. 5. Such generosity was probably not energetically
      sustainable as these male partners took on less incubation in the 72 h following
      handicapping compared to female partners of handicapped males. Males and females
      are probably generous in the short-term because of the high cost of nest failure
      during incubation but maintaining increased work loads in the longer term is
      probably limited by body condition and abandonment thresholds consistent with
      game theory models.

PMID- 19744254
TI  - CBT for childhood anxiety disorders: differential changes in selective attention
      between treatment responders and non-responders.
AB  - BACKGROUND: This study examined whether treatment response to stepped-care
      cognitive-behavioural treatment (CBT) is associated with changes in threat
      related selective attention and its specific components in a large clinical
      sample of anxiety-disordered children. METHODS: Ninety-one children with an
      anxiety disorder were included in the present study. Children received a
      standardized stepped-care CBT. Three treatment response groups were
      distinguished: initial responders (anxiety disorder free after phase one: child
      focused CBT), secondary responders (anxiety disorder free after phase two: child
      parent-focused CBT), and treatment non-responders. Treatment response was
      determined using a semi-structured clinical interview. Children performed a
      pictorial dot-probe task before and after stepped-care CBT (i.e., before phase
      one and after phase two CBT). RESULTS: Changes in selective attention to severely
      threatening pictures, but not to mildly threatening pictures, were significantly
      associated with treatment success. At pre-treatment assessment, initial
      responders selectively attended away from severely threatening pictures, whereas
      secondary responders selectively attended toward severely threatening pictures.
      After stepped-care CBT, initial and secondary responders did not show any
      selectivity in the attentional processing of severely threatening pictures.
      Treatment non-responders did not show any changes in selective attention due to
      CBT. CONCLUSIONS: Initial and secondary treatment responders showed a reduction
      of their predisposition to selectively attend away or toward severely threatening
      pictures, respectively. Treatment non-responders did not show any changes in
      selective attention. The pictorial dot-probe task can be considered a potentially
      valuable tool in assigning children to appropriate treatment formats as well as
      for monitoring changes in selective attention during the course of CBT.

PMID- 19744255
TI  - Adjuvant topical therapy with a cannabinoid receptor agonist in facial
      postherpetic neuralgia.
AB  - BACKGROUND: Postherpetic neuralgia is a frequent adverse event in herpes zoster
      patients and difficult to treat. Conventional analgetic therapy often fails to
      reduce the burning pain transmitted by unmyelinated nerve fibers. These nerves
      express cannabinoid receptors which exert a role in modulation of nociceptive
      symptoms. Therefore, topical therapy with cannabinoid receptor agonist seems
      likely to suppress local burning pain. PATIENTS AND METHODS: In an open-labeled
      trial, 8 patients with facial postherpetic neuralgia received a cream containing
      the cannabinoid receptor agonist N-palmitoylethanolamine. The course of symptoms
      was scored with the visual analog scale. RESULTS: 5 of 8 patients (62.5 %)
      experienced a mean pain reduction of 87.8 %. Therapy was tolerated by all
      patients. No unpleasant sensations or adverse events occurred. CONCLUSIONS:
      Topical cannabinoid receptor agonists are an effective and well-tolerated
      adjuvant therapy option in postherpetic neuralgia.

PMID- 19744256
TI  - Unit cost of Mohs and Dermasurgery Unit.
AB  - BACKGROUND: Appropriate pricing for medical services of not-for-profit hospital
      is necessary. The prices should be fair to the public and should be high enough
      to cover the operative costs of the organization. OBJECTIVE: The purpose of this
      study was to determine the cost and unit cost of medical services performed at
      the Mohs and Dermasurgery Unit (MDU), Department of Dermatology, The University
      of Texas-MD Anderson Cancer Center, Houston, TX from the healthcare provider's
      perspective. METHODS: MDU costs were retrieved from the Financial Department for
      fiscal year 2006. The patients' statistics were acquired from medical records for
      the same period. Unit cost calculation was based on the official method of
      hospital accounting. RESULTS: The overall unit cost for each patient visit was
      $673.99 United States dollar (USD). The detailed unit cost of nurse visit, new
      patient visit, follow-up visit, consultation, Mohs and non-Mohs procedure were,
      respectively, $368.27, $580.09, $477.82, $585.52, $1,086.12 and $858.23 USD. With
      respect to a Mohs visit, the unit cost per lesion and unit cost per stage were
      $867.89 and $242.30 USD respectively. CONCLUSIONS: Results from this
      retrospective study provide information that may be used for pricing strategy and
      resource allocation by the administrative board of MDU.

PMID- 19744257
TI  - Control of negative emotions and its implication for illness perception among
      psoriasis and vitiligo patients.
AB  - BACKGROUND: The purpose of the study was to determine the intensity of control
      over negative emotions of anger, depressed mood, and anxiety in certain skin
      diseases such as psoriasis and vitiligo, and to define the predictors of this
      emotional control in terms of the illness perception in the following context:
      duration of illness, age at onset, subjective knowledge of the causes of illness,
      subjective sense of control over the disease. METHODS: The study included 60
      patients with psoriasis (n = 30) and vitiligo (n = 30) as well as healthy persons
      (n = 60) matched to the experimental group in terms of gender, age, and level of
      education. Control of negative emotions was examined by means of Watson and
      Greer's Courtauld Emotional Control Scale (Polish adaptation by Juczynski) and
      the illness perception by means of Kossakowska's Chronic Patients Questionnaire.
      RESULTS: The research concludes that psoriasis patients control negative emotions
      more intensively than healthy people. Vitiligo patients on the other hand do not
      differ in the control of negative emotions compared with healthy subjects. There
      are no significant predictors of negative emotional control in vitiligo. In
      psoriasis gender and age are the main contributors to negative emotional control
      and anger control is predicted by the age at onset as well. CONCLUSION: The
      specificity of the skin disease affects maladaptive negative emotional control
      and the suggestion is to use psychological treatment in hospitalised psoriasis in
      particular.

PMID- 19744258
TI  - Adnexal tumours of the skin as markers of cancer-prone syndromes.
AB  - Adnexal tumours of the skin are benign, more rarely malignant, primary skin
      tumours that originate from, or differentiate towards, hair follicles, sebaceous
      and sweat glands. Although they are usually encountered as single, sporadic
      tumours, they may occasionally be multiple, hereditary; in that case, they may
      herald complex genetic syndromes that comprise visceral cancers. Dermatologists
      should be aware of these adnexal skin tumours, the diagnosis of which may
      contribute to an early detection of a cancer-prone syndrome with a potentially
      lethal outcome. The main tumours falling into this category and their associated
      syndromes are reviewed here.

PMID- 19744259
TI  - Intralesional sodium stibogluconate alone or its combination with either
      intramuscular sodium stibogluconate or oral ketoconazole in the treatment of
      localized cutaneous leishmaniasis: a comparative study.
AB  - BACKGROUND: Cutaneous leishmaniasis (CL) is a disease caused by leishmania
      species. Intralesional sodium stibogluconate (SSG) has been considered the first
      line therapy for localized cutaneous leishmaniasis. There is still a need for
      more effective and less time-consuming therapeutic methods for this condition.
      OBJECTIVE: The aim of the present study was to investigate if the combination of
      intramuscular (IM) SSG or oral ketoconazole with intralesional (IL) SSG would be
      more effective than the intralesional SSG given alone in the treatment of
      localized cutaneous leishmaniasis. PATIENTS AND METHODS: Thirty patients with
      confirmed diagnosis of cutaneous leishmaniasis were included in the study. They
      were randomly assigned to three groups. The first group (10 patients with 12
      lesions) was treated with intralesional SSG alone. The second group (10 patients
      with 15 lesions) was treated with the combination of intralesional SSG +
      intramuscular SSG. The third group (10 patients with 13 lesions) was treated with
      the combination of intralesional SSG and oral ketoconazole. A follow-up was
      performed every 4 weeks for a treatment period of 12 weeks, then monthly for a
      period of 6 months after the end of the treatment. RESULTS: Complete cure
      occurred in 58.3% of lesions in group 1, while 93.3% and 92.3% of lesions were
      cured in group 2 and 3 respectively. The difference between group 1 and the other
      groups was statistically significant (P < 0.05). CONCLUSION: Combined
      intramuscular SSG or oral ketoconazole with intralesional SSG is more effective
      than intralesional SSG alone for the treatment of CL. Oral ketoconazole is much
      easier and safer therapy than intramuscular SSG in combination with intralesional
      SSG in the treatment of localized cutaneous leishmaniasis.

PMID- 19744260
TI  - The effect of an intervention aimed at reducing errors when administering
      medication through enteral feeding tubes in an institution for individuals with
      intellectual disability.
AB  - BACKGROUND: Previous studies, both in hospitals and in institutions for clients
      with an intellectual disability (ID), have shown that medication errors at the
      administration stage are frequent, especially when medication has to be
      administered through an enteral feeding tube. In hospitals a specially designed
      intervention programme has proven to be effective in reducing these feeding tube
      related medication errors, but the effect of such a programme within an
      institution for clients with an ID is unknown. Therefore, a study was designed to
      measure the influence of such an intervention programme on the number of
      medication administration errors in clients with an ID who also have enteral
      feeding tubes. METHODS: A before-after study design with disguised observation to
      document administration errors was used. The study was conducted from February to
      June 2008 within an institution for individuals with an ID in the Western part of
      The Netherlands. Included were clients with enteral feeding tubes. The
      intervention consisted of advice on medication administration through enteral
      feeding tubes by the pharmacist, a training programme and introduction of a
      'medication through tube' box containing proper materials for crushing and
      suspending tablets. The outcome measure was the frequency of medication
      administration errors, comparing the pre-intervention period with the post
      intervention period. RESULTS: A total of 245 medication administrations in six
      clients (by 23 nurse attendants) have been observed in the pre-intervention
      measurement period and 229 medication administrations in five clients (by 20
      nurse attendants) have been observed in the post-intervention period. Before the
      intervention, 158 (64.5%) medication administration errors were observed, and
      after the intervention, this decreased to 69 (30.1%). Of all potential
      confounders and effect modifiers, only 'medication dispensed in automated
      dispensing system ("robot") packaging' contributed to the multivariate model;
      effect modification was shown for this determinant. Multilevel analysis using
      this multivariate model resulted in an odds ratio of 0.33 (95% confidence
      interval 0.13-0.71) for the error percentage in the post-intervention period
      compared with the pre-intervention period. CONCLUSIONS: The intervention was
      found to be effective in an institution for clients with an ID. However,
      additional efforts are needed to reduce the proportion of administration errors
      which is still high after the intervention.

PMID- 19744261
TI  - Hope as a psychological resilience factor in mothers and fathers of children with
      intellectual disabilities.
AB  - BACKGROUND: Positive psychology is an area gaining credence within the field of
      intellectual disability (ID). Hope is one facet of positive psychology that is
      relatively unstudied in parents of children with ID. In the present study, we
      explore hope and its relationships with parental well-being in parents of school
      aged children with ID. METHOD: A total of 138 mothers and 58 fathers of children
      with ID took part in a questionnaire-based study. Parents reported on their
      feelings of hope and positive affect, other dimensions of psychological well
      being (anxiety, depression and stress), and on their child's behaviour. For this
      study, hope was measured as a goal driven behaviour comprising two components:
      agency (the perception that one can reach his/her goals) and pathways (the
      perception that one can find alternative routes to reach these goals should the
      need arise). RESULTS: For mothers, regression analyses revealed that lower levels
      of hope (agency and pathways) and more child behaviour problems predicted
      maternal depression. Positive affect was predicted by less problematic child
      behaviour and by higher levels of hope agency. For fathers, anxiety and
      depression were predicted by low hope agency and positive affect was predicted by
      high hope agency. Hope pathways was not a significant predictor of paternal well
      being. Hope agency and pathways interacted in the prediction of maternal
      depression such that mothers reporting high levels of both hope dimensions
      reported the lowest levels of depressive symptoms. CONCLUSIONS: Hope is a
      construct that merits further investigation within families research, and is
      potentially a factor that could be utilised in intervention to help increase
      familial well-being.

PMID- 19744262
TI  - Cognitive function and number of teeth in a community-dwelling elderly population
      without dementia.
AB  - Although the number of sound or decayed teeth has been reported to be associated
      with cognitive function in elderly populations with dementia, little is known
      about this association in elderly populations without dementia. We evaluated this
      relationship, with adjustment for confounding factors, in Japanese populations of
      60-year-old (n = 270; 120 males and 150 females) and 65-year-old (n = 123; 57
      males and 66 females) individuals residing in Fukuoka Prefecture of Japan. Dental
      examinations were performed in all subjects, along with the Mini-mental state
      examination (MMSE) for assessing cognitive function. Among the total of 393
      subjects, the mean MMSE score was 27.9 +/- 1.9, and 391 subjects scored 24 or
      higher. The mean numbers of sound and decayed teeth were 12.0 +/- 6.3 and 0.5 +/-
      1.2, respectively. Associations were found between the numbers of sound and
      decayed teeth and MMSE in total subjects and males, but not in females, by
      multiple regression analysis adjusted for gender, age, level of education,
      marital status, smoking, alcohol drinking, working status, systolic blood
      pressure and blood glucose. An association was also found between MMSE and the
      number of sound teeth in a logistic regression analysis. In conclusion,
      associations were found between normal-range cognitive function and the numbers
      of sound and decayed teeth, after adjustment for various confounding factors, in
      an elderly Japanese population.

PMID- 19744263
TI  - The effects of fixed orthodontic appliances on saliva flow rate and saliva
      electrolyte concentrations.
AB  - Fixed appliance orthodontic treatment may affect local saliva secretion; however,
      there is limited information available about this respect in the literature.
      Understanding how fixed appliance orthodontic treatment affects local saliva
      secretion could provide insight on possible contributions of salivary changes
      towards decalcification. In this study, we found that during the first month of
      fixed orthodontic treatment, the whole saliva flow rate, upper labial saliva flow
      rate and concentrations of whole saliva sodium and chlorine increased
      significantly, while the concentrations of calcium, phosphorous and potassium in
      whole saliva decreased. However, all these were in normal levels after 3 months.
      This study demonstrated that saliva flow rate was increased and saliva
      electrolytes were changed at early stage when placing fixed orthodontic
      appliances, which was considered due to increased mechanosensation.

PMID- 19744264
TI  - Clinical evaluation of Procera AllCeram crowns in Japanese patients: results
      after 5 years.
AB  - Procera AllCeram crowns were prospectively evaluated clinically in both anterior
      and posterior regions in Japanese. One-hundred and one crowns were fabricated for
      57 patients at the Tsurumi University Dental Hospital from August 2001 to October
      2002 and evaluated according to the California Dental Association (CDA) quality
      evaluation system at baseline and annually at all follow-up examinations for 5
      years. The plaque index (PI) and gingival index (GI) were recorded, and chipping
      and fracture were checked at the same time as well. A total of 75 Procera
      AllCeram crowns were evaluated, and the cumulative survival rate was 90.2% over
      the 5-year clinical trial. Six crowns experienced fractures within the veneering
      porcelain and from aluminium oxide coping, all of which occurred on the premolar
      and molar regions, and they had to be removed. Small chipping was observed on
      three crowns. According to the CDA criteria, 98% of Procera AllCeram crowns were
      rated as satisfactory, and PI and GI were comparable to those of control teeth
      during the observation period.

PMID- 19744265
TI  - Relationship of smoking and smoking cessation with oral health status in Japanese
      men.
AB  - BACKGROUND AND OBJECTIVE: Smoking has been associated with the number of natural
      teeth a person has and with the likelihood of periodontitis. The purpose of this
      study was to determine the relationships between the number of teeth present and
      periodontal diseases with smoking habits in a cohort of Japanese men. MATERIAL
      AND METHODS: The study group comprised 1088 men, 40-75 years of age. Oral
      examinations were conducted in dental clinics. Information on smoking status and
      on oral health behavior was collected from self-administered questionnaires. The
      relationship between oral health status and smoking status was estimated using
      adjusted odds ratios. RESULTS: Compared with those whom had never smoked, the
      odds ratios of having more than eight missing teeth and having periodontitis,
      among current smokers, were 1.67 and 1.74, respectively. In those who had stopped
      smoking for 11 years or longer, there was no increase in the odds ratio of having
      more than eight missing teeth and periodontitis, compared with those whom had
      never smoked. CONCLUSION: Smoking has a positive association with missing teeth
      and periodontitis. However, smoking cessation is beneficial for oral health. The
      odds of having more than eight missing teeth, or of having periodontitis, in
      those who had never smoked was similar to that of individuals who reported that
      they had stopped smoking for 11 years or more.

PMID- 19744266
TI  - Z and Mmalton-1-antitrypsin deficiency-associated hepatocellular carcinoma: a
      genetic study.
AB  - BACKGROUND: The histological hallmark of alpha-1-antitrypsin deficiency (AATD) is
      the presence of periodic acid-Schiff diastase (PASD)-resistant positive globules
      in hepatocytes, with a heterogeneous distribution. It is noteworthy that
      hepatocellular carcinoma (HCC) arises specifically from the AAT-negative areas
      but the reason for this remains unclear. AIM: To determine whether the different
      distribution of AAT globules within neoplastic and non-neoplastic hepatocytes is
      the result of a self-induced correction of the genetic defect. PATIENTS AND
      METHODS: Two HCV-positive patients with AATD-associated HCC were studied. One
      patient harboured a compound heterozygous PiSZ genotype whereas the other showed
      the rarer PiMMmalton in heterozygosity. In both cases, neoplastic hepatocytes
      appeared globule devoid, while non-neoplastic hepatocytes showed intracytoplasmic
      accumulation of PASD-positive globules. Laser-assisted microdissection was used
      to assess a genotype/phenotype correlation in single liver cells from HCC and
      from non-neoplastic hepatocytes. RESULTS: Direct sequencing of DNA purified from
      globule-devoid and globule-filled hepatocytes demonstrated that all liver cells
      carried the same mutant genetic background. CONCLUSION: Our findings indicate
      that (i) both variants of HCC arising in AAT deficiency (Z and Mmalton) do not
      accumulate the mutant protein and (ii) the different phenotypic appearance of
      hepatocytes is not the result of a retromutation during neoplastic
      transformation, but other mechanisms should be investigated.

PMID- 19744267
TI  - The queen is dead--long live the workers: intraspecific parasitism by workers in
      the stingless bee Melipona scutellaris.
AB  - Insect societies are well known for their high degree of cooperation, but their
      colonies can potentially be exploited by reproductive workers who lay
      unfertilized, male eggs, rather than work for the good of the colony. Recently,
      it has also been discovered that workers in bumblebees and Asian honeybees can
      succeed in entering and parasitizing unrelated colonies to produce their own male
      offspring. The aim of this study was to investigate whether such intraspecific
      worker parasitism might also occur in stingless bees, another group of highly
      social bees. Based on a large-scale genetic study of the species Melipona
      scutellaris, and the genotyping of nearly 600 males from 45 colonies, we show
      that approximately 20% of all males are workers' sons, but that around 80% of
      these had genotypes that were incompatible with them being the sons of workers of
      the resident queen. By tracking colonies over multiple generations, we show that
      these males were not produced by drifted workers, but rather by workers that were
      the offspring of a previous, superseded queen. This means that uniquely, workers
      reproductively parasitize the next-generation workforce. Our results are
      surprising given that most colonies were sampled many months after the previous
      queen had died and that workers normally only have a life expectancy of
      approximately 30 days. It also implies that reproductive workers greatly outlive
      all other workers. We explain our results in the context of kin selection theory,
      and the fact that it pays workers more from exploiting the colony if costs are
      carried by less related individuals.

PMID- 19744268
TI  - Arrhythmogenic right ventricular cardiomyopathy in an octogenarian presenting
      with ventricular tachycardia.
AB  - Arrhythmogenic right ventricular cardiomyopathy (ARVC) is one of the major causes
      of sudden death. Myocardial atrophy with subsequent fibro-fatty replacement
      predominantly affects right ventricular myocardium and results in global and
      regional dysfunction as well as areas of slow conduction and dispersion of
      refractoriness, which are prerequisites for reentrant ventricular
      tachyarrhythmias. ARVC is commonly presented in patients <65 years old. However,
      few cases of elderly people suffering from this cardiomyopathy have been reported
      in the literature. We present a case of an 82-year-old woman with sustained
      ventricular tachycardia due to first diagnosed ARVC.

PMID- 19744269
TI  - Transatrial lead implantation using the 4-Fr lumenless pacing lead and delivery
      system in young adults with congenital heart disease.
AB  - We report the technique of transatrial delivery of the Medtronic 3830
      SelectSecure lead (Medtronic Inc., Minneapolis, MN, USA) for right ventricular
      endocardial pacing in two young adults with congenital heart disease who had
      multiple pacing lead failures and superior vena cava occlusion. The deflectable
      catheter delivery system used to position the SelectSecure lead provided the
      opportunity to map the right ventricular endocardial surface and determine the
      best available pacing site. At midterm follow-up, both systems are functioning
      well.

PMID- 19744270
TI  - Acute perforation in spite of implantation with an "antiperforation"
      defibrillator lead.
AB  - A 74-year-old male underwent implantation of implantable cardioverter
      defibrillator per multicenter automatic defibrillator trial two criteria. The new
      St. Jude Medical Riata STS Durata defibrillator lead (St. Jude Medical, Sylmar,
      CA, USA) was used. This lead has a slight curve at the right ventricle shock coil
      and a silicone tip designed to decrease tip pressure at the endocardium
      interface. We presented a case of acute perforation during implantation of this
      lead. The patient was treated with pericardiocentesis and recovered.

PMID- 19744271
TI  - Ventricular tachycardia in a patient with inclusion-body myositis.
AB  - We report a patient with a clinical history of inclusion-body myositis presenting
      with monomorphic ventricular tachycardia. Comprehensive evaluation demonstrated
      no evidence of coronary artery disease or cardiomyopathy. Programmed electrical
      stimulation induced the patient's clinical tachycardia as well as a second
      monomorphic ventricular tachycardia of a different morphology. At the time of
      implantable cardioverter-defibrillator implant, biopsy of the pectoralis major
      muscle was performed, which confirmed the diagnosis of inclusion-body myositis.
      Ventricular tachycardia has not previously been reported in a patient with
      inclusion-body myositis.

PMID- 19744272
TI  - Detection of a retention wire fracture in an asymptomatic patient 18 years after
      implantation.
AB  - An asymptomatic patient with a Teletronics Accufix atrial lead (Teletronics,
      Englewood, CO, USA) presented for an annual fluoroscopic examination. The
      examination revealed a retention wire fracture, which occurred 18 years after the
      initial implantation. Annual fluoroscopic examination of these leads should still
      be performed.

PMID- 19744273
TI  - A transbaffle approach to ablation in a child with an extracardiac fontan.
AB  - We present the case of an 11-year-old with D-transposition, double inlet left
      ventricle, and dextrocardia 8 years following an extracardiac Fontan with
      supraventricular tachycardia mediated by a concealed accessory pathway. A
      transbaffle puncture was performed with fluoroscopic and transesophageal
      echocardiography guidance and the pathway location as well as its proximity to
      the HIS bundle were identified. The pathway was successfully ablated and the
      patient is asymptomatic for 12 months postablation.

PMID- 19744274
TI  - Supraventricular arrhythmia induction by an implantable cardioverter
      defibrillator in a patient with hypertrophic cardiomyopathy.
AB  - A 23-year-old woman with obstructive hypertrophic cardiomyopathy and history of
      frequent unexplained syncope had undergone implantable cardioverter defibrillator
      implantation. She had experienced frequent inappropriate shocks since
      implantation due to T-wave oversensing. After one of the syncopal attacks, she
      was found to have an atrioventricular (AV)-reentrant tachycardia, induced by a
      high-voltage shock, with rapid degeneration to atrial fibrillation and then
      ventricular fibrillation. The AV-reentrant tachycardia was believed to be the
      cause of both syncopal attacks and inappropriate shocks. The patient has been
      asymptomatic after ablation of the accessory pathway. To the best of our
      knowledge, this is the first report of induction of an AV-reentrant tachycardia
      by a high-voltage implantable cardioverter defibrillator shock.

PMID- 19744275
TI  - Two ventricular tachycardias with cycle length and QRS alternans: insights into
      the mechanism from mapping and ablation of the tachycardias.
AB  - This case describes a patient with two separate foci of idiopathic ventricular
      tachycardia in the right ventricle. Both of the tachycardias manifested cycle
      length and QRS alternans. Both were successfully ablated and information from the
      electrophysiologic study and ablation procedure indicated that both tachycardias
      were focal, secondary to triggered activity, and that the best model to explain
      the cycle length and QRS alternans during tachycardia was that of "self
      entraining modulated parasystole."

PMID- 19744276
TI  - Recurrent ventricular tachycardia in patient with Friedreich's ataxia in the
      absence of clinical myocardial disease.
AB  - We report a 33-year-old man with recurrent loss of consciousness due to
      ventricular tachyarrhythmia with a history of Friedreich's ataxia. The patient's
      symptom was improved after implantation of a single-lead implantable cardiac
      defibrillator. The clinical, genetic, echocardiographic, and electrocardiographic
      features are discussed in brief.

PMID- 19744277
TI  - Magnesium sensitive, adenosine resistant, repetitive monomorphic ventricular
      tachycardia.
AB  - Repetitive monomorphic ventricular tachycardia (RMVT) is characterized by
      episodes of ventricular ectopy and nonsustained VT exacerbated by catecholamines.
      Because this arrhythmia is frequently adenosine sensitive, its mechanism is
      believed to be cyclic adenosine monophosphate-mediated triggered activity due to
      delayed afterdepolarizations. We present a case of RMVT associated with
      significant hypomagnesemia (serum level = 1.1 mg/dL), which did not respond to
      intravenous (IV) adenosine and terminated repeatedly after IV magnesium.
      Electrophysiologic study demonstrated an origin from the left sinus of Valsalva,
      which was successfully ablated. The combination of adenosine resistance and
      magnesium sensitivity may be consistent with an atypical RMVT mechanism related
      to inhibition of sodium-potassium adenosine triphosphatase (Na(+)-K(+) ATPase).

PMID- 19744278
TI  - Pharmacotherapy of cardiac arrhythmias--basic science for clinicians.
AB  - Cardiac arrhythmias occur in approximately 5.3% of the population and contribute
      substantially to morbidity and mortality. Pharmacological therapy still remains
      the major approach in management of patients with nearly every form of cardiac
      arrhythmia. Effective and safe management of cardiac arrhythmias with
      antiarrhythmic drugs requires understanding of basic mechanisms for various
      cardiac arrhythmias, clinical diagnosis of an arrhythmia and identification of
      underlying cardiac diseases, pharmacokinetics, and antiarrhythmic properties of
      each individual antiarrhythmic drug. Most cardiac arrhythmias occur via one of
      the two mechanisms: abnormal impulse formation and reentry or both.
      Antiarrhythmic drugs primarily work via influencing cardiac automaticity or
      triggered activity or by their effects on effective refractoriness of cardiac
      cells. Proarrhythmic effects of antiarrhythmic drugs are also briefly discussed
      in this review article.

PMID- 19744280
TI  - Identification of AF drivers: toward a mechanistic basis of AF ablation.

PMID- 19744279
TI  - Centrifugal gradients of rate and organization in human atrial fibrillation.
AB  - INTRODUCTION: Animal studies show that atrial fibrillation (AF) may emanate from
      sites of high rate and regularity, with fibrillatory conduction to adjacent
      areas. We used simultaneous mapping to find evidence for potential drivers in
      human AF defined as sites with higher rate and regularity than surrounding
      tissue. MATERIALS AND METHODS: In 24 patients (age 61+/-10 years; 12 persistent),
      we recorded AF simultaneously from 32 left atrial bipolar basket electrodes in
      addition to pulmonary veins (PV), coronary sinus, and right atrial electrodes. We
      measured AF cycle length (CL) by Fourier transform and electrogram regularity at
      each electrode, referenced to patient-specific atrial anatomy. RESULTS: We
      analyzed 10,298 electrode-periods. Evidence for potential AF drivers was found in
      11 patients (five persistent). In persistent AF, these sites lay at the coronary
      sinus and left atrial roof but not PVs, while in paroxysmal AF six of nine sites
      lay at PVs (P<0.05). During ablation, a subset of patients experienced AF CL
      prolongation or termination with a focal lesion; in each case this lesion mapped
      to potential driver sites on blinded analysis. Conversely, sequential mapping
      failed to reveal these sites, possibly due to fluctuations in dominant frequency
      at driver locations in the context of migratory AF. CONCLUSIONS: Simultaneous
      multisite recordings in human AF reveal evidence for drivers that lie near PVs in
      paroxysmal but not persistent AF, and were sites where ablation slowed or
      terminated AF in a subset of patients. The future work should determine if real
      time ablation of AF-maintaining regions defined in this fashion eliminates AF.

PMID- 19744281
TI  - Different mechanisms underlying consecutive, postoperative atrial
      tachyarrhythmias in a Fontan patient.
AB  - INTRODUCTION: Atrial tachyarrhythmias (AT) frequently develop later after a
      Fontan operation and can be successfully treated by ablative therapy. However,
      new arrhythmias often develop. METHODS AND RESULTS: Consecutive AT emerging in a
      Fontan patient were ablated using three-dimensional electro-anatomical mapping.
      During a 6-year period, nine different AT were ablated, including intraatrial
      reentrant AT (N=5), focal AT (N=3), and focal atrial fibrillation (N=1)
      originating from distinct right atrial sites. CONCLUSION: In a Fontan patient,
      successive AT can be caused by different mechanisms. These AT are most likely the
      result of progressive atrial cardiomyopathy and can be treated by catheter
      ablation.

PMID- 19744282
TI  - Indirect immunohistochemical evaluation of graft fibrosis and interface hepatitis
      after pediatric liver transplantation.
AB  - Fibrosis or IH following pediatric liver transplantation is recognized as major
      causes of graft loss, but the etiology remains unclear. To determine this issue,
      we used an indirect immunohistochemistry technique with post-transplant serum
      samples from recipients and normal human liver tissues from living liver donors,
      and the association between occult antibody reaction to the liver and the
      occurrence of fibrosis or IH was evaluated. Forty-three recipients were
      evaluated, and both hepatocytes and biliary epithelial cells were evaluated for
      staining intensity. Fibrosis and IH occurred in 13 and six patients,
      respectively. According to staining results for the hepatocytes and biliary
      epithelial cells, 18 and 11 patients, respectively, were classified into the
      positive group. According to log-rank analysis, positive reaction for hepatocytes
      was associated with increased rates of fibrosis and IH (p = 0.002 and 0.048,
      respectively), while positive reaction for biliary epithelial cells was
      associated with an increased rate of fibrosis (p = 0.014). Multivariate analysis
      revealed that positive reaction for hepatocytes and biliary epithelial cells was
      independently associated with fibrosis occurrence (p = 0.020 and 0.047,
      respectively). In conclusion, immune-mediated reactions by occult antibodies may
      underlie the pathogeneses of fibrosis and IH.

PMID- 19744283
TI  - Ab initio calcineurin inhibitor-based monotherapy immunosuppression after liver
      transplantation reduces the risk for Pneumocystis jirovecii pneumonia.
AB  - At the Tor Vergata University of Rome, ab initio calcineurin inhibitor-based
      monotherapy immunosuppression (IS) is the standard of treatment after liver
      transplantation (LT). As the net state of IS determines the onset of Pneumocystis
      jirovecii pneumonia (PCP), we hypothesized that, in the presence of weak
      impairment of the immune function, as determined by the above-mentioned IS, the
      host is not overexposed to the risk for PCP and consequently the specific anti
      PCP prophylaxis is unnecessary. In a single-cohort descriptive study, we
      retrospectively investigated the incidence of PCP in 203 LT patients who did not
      receive anti-PCP prophylaxis because they were under monotherapy IS. The primary
      endpoint of the study was the incidence of PCP during the first 12 months
      following LT; secondary endpoints were the incidence of acute rejection requiring
      additional IS and of CMV infection. No cases of PCP were recorded. The incidence
      of CMV and acute rejection was 3.9% and 0.9%, respectively. Our data suggest that
      monotherapy IS after LT may nullify the risk for PCP even in the absence of any
      specific prophylaxis.

PMID- 19744284
TI  - Lower incidence of cytomegalovirus infection with everolimus versus mycophenolate
      mofetil in de novo cardiac transplant recipients: a randomized, multicenter
      study.
AB  - Cytomegalovirus (CMV) is a major cause of infectious complications following
      cardiac transplantation, severely affecting short- and long-term outcomes. A 12
      month, multicenter, randomized, open-label study in de novo cardiac transplant
      patients was undertaken to compare the efficacy, renal function, and safety of
      everolimus plus reduced cyclosporine versus mycophenolate mofetil (MMF) plus
      standard cyclosporine (ClinicalTrials.gov NCT00150046). CMV-specific data was
      prospectively collected on infections, laboratory evidence, CMV syndrome, and CMV
      disease. In total, 176 patients were randomized (everolimus 92; MMF 84). Use of
      CMV prophylaxis was similar between groups (everolimus 20.8%; MMF 24.0%).
      Patients in the everolimus arm had a significantly lower incidence of any CMV
      event (8.8% versus 32.5% with MMF, P<0.001), CMV infection as an adverse event
      (4.4% versus 16.9%, P=0.011), laboratory evidence of CMV (antigenemia 7.7% versus
      27.7%, P<0.001; polymerase chain reaction assay 2.2% versus 12.0%, P=0.015), and
      CMV syndrome (1.1% versus 8.4%, P=0.028). In the donor (D)+/recipient (R)+and D
      /R+ subgroups, even after adjusting for use of prophylaxis, the CMV event rate
      remained significantly lower with everolimus than with MMF (P=0.0015 and
      P=0.0381, respectively). In conclusion, de novo cardiac transplant recipients
      experienced lower rates of CMV infection, CMV syndrome, or organ involvement on
      an everolimus-based immunosuppressant regimen compared with MMF.

PMID- 19744285
TI  - Molecular evidence of interhuman transmission in an outbreak of Pneumocystis
      jirovecii pneumonia among renal transplant recipients.
AB  - Pneumocystis jirovecii pneumonia (PCP) remains an important cause of morbidity
      and mortality in immunocompromised individuals. The epidemiology and pathogenesis
      of this infection are poorly understood, and the exact mode of transmission
      remains unclear. Recent studies reported clusters of PCP among immunocompromised
      patients, raising the suspicion of interhuman transmission. An unexpected
      increase of the incidence of PCP cases in our nephrology outpatient clinic
      prompted us to conduct a detailed analysis. Genotyping of 7 available specimens
      obtained from renal transplant recipients was performed using multi-locus DNA
      sequence typing (MLST). Fragments of 4 variable regions of the P. jirovecii
      genome (ITS1, 26S, mt26S, beta-tubulin) were sequenced and compared with those of
      4 independent control patients. MLST analysis revealed identical sequences of the
      4 regions among all 7 renal allograft recipients with available samples,
      indicating an infection with the same P. jirovecii genotype. We observed that all
      but 1 of the 19 PCP-infected transplant recipients had at least 1 concomitant
      visit with another PCP-infected patient within a common waiting area. This study
      provides evidence that nosocomial transmission among immunocompromised patients
      may have occurred in our nephrology outpatient clinic. Our findings have
      epidemiological implications and suggest that prolonged chemoprophylaxis for PCP
      may be warranted in an era of more intense immunosuppression.

PMID- 19744286
TI  - Kinetics of interferon-gamma producing cytomegalovirus (CMV)-specific CD4+ and
      CD8+ T lymphocytes and the risk of subsequent CMV viremia after allogeneic
      hematopoietic stem cell transplantation.
AB  - BACKGROUND: Deficiencies in cytomegalovirus (CMV)-specific T lymphocytes impair
      the immunologic response against CMV reactivation after allogeneic hematopoietic
      stem cell transplantation (HSCT). METHODS: A time-dependent analysis was
      conducted to determine the association between the percentages and kinetics of
      interferon-gamma-producing CMV-specific CD4+ and CD8+ T lymphocytes and CMV
      viremia among 30 allogeneic HSCT recipients. RESULTS: Higher percentages of CD4+
      T lymphocytes activated with CMVpp65 (hazard ratio [HR]: 2.06; 95% confidence
      interval [95% CI]: 1.18-3.6; P=0.011) and CMV lysate (HR: 1.18; 95% CI: 0.99
      1.42; P=0.072), and higher percentages of CD8+ T lymphocytes activated by CMV
      immediate early-1 (HR: 1.2; 95% CI: 1.01-1.43; P=0.038) and CMVpp65 (HR: 1.12;
      95% CI: 1.0-1.27; P=0.060) were associated with time-to-CMV viremia. Furthermore,
      a higher degree in the decline of CMV lysate-activated CD4+ T lymphocytes (HR:
      1.14; 95% CI: 0.96-1.36; P=0.125) and CMVpp65-activated CD8+ T lymphocytes (HR:
      1.36; 95% CI: 1.03-1.78; P=0.031) was suggestive of or significantly associated
      with time-to-CMV viremia. CONCLUSIONS: Higher levels of CMV-specific CD4+ and
      CD8+ T lymphocytes were associated with subsequent CMV viremia after HSCT. The
      association between CMV viremia and the degree of decline in CMV-specific T
      lymphocytes suggests that severe disruption in homeostatic CMV-specific immune
      environment contributes to the immunopathogenesis of CMV after allogeneic HSCT.

PMID- 19744287
TI  - Faith leaders united in their support for organ donation: findings from the UK
      Organ Donation Taskforce study.
AB  - SUMMARY: This article reports the findings from the one-to-one interviews with
      the main UK faith and belief leaders, which were commissioned by the Organ
      Donation Taskforce. Interviews were arranged with the main faith and belief
      organizations within the UK and covered a range of issues related to organ
      donation. No faith or belief groups were against organ donation in principle. The
      interviewees stated that the majority opinion in their faith or belief group is
      to permit organ donation, with some actively supporting it. Interviewees were
      keen to stress that there is a broad spectrum of opinions on organ
      transplantation within each faith and belief group, and that consequently it is
      difficult to speak on behalf of an entire group. One complication mentioned by
      interviewees is that as organ transplantation is a relatively new medical
      procedure, there is no explicit reference to it in many original religious texts.
      Consequently positions on the receipt and donation of organs are based on
      interpretation. It was felt that a much greater level of engagement is needed, as
      organ donation is currently not a priority for many faith and belief groups.

PMID- 19744288
TI  - Health state valuations of patients and the general public analytically compared:
      a meta-analytical comparison of patient and population health state utilities.
AB  - OBJECTIVES: To obtain quality-adjusted life-years, different respondent groups,
      such as patients or the general public, may be asked to value health states.
      Until now, it remains unclear if the respondent group has an influence on the
      values obtained. We assessed this issue through meta-analysis. METHODS: A
      literature search was performed for studies reporting valuations given by
      patients and nonpatients. Studies using indirect utility instruments were
      excluded. RESULTS: From 30 eligible studies, 40 estimators were retrieved
      revealing a difference between respondent group (Cohen's d=0.20, P<0.01). When
      elicitation methods were analyzed separately, patients gave higher valuations
      than nonpatients using the time trade-off (TTO) (N=25, unstandardized d=0.05,
      P<0.05) and the visual analog scale (VAS) (N=22, unstandardized d=0.04, P<0.05).
      When the standard gamble was used, no difference was seen (N=24, unstandardized
      d=0.01, P=0.70). CONCLUSION: In contrast with Dolders et al., our results show
      that patients give higher valuations than members of the general public. For
      future cost-utility analyses, researchers should be aware of the differential
      effects of respondent group for the elicitation methods TTO and VAS.

PMID- 19744289
TI  - A concept taxonomy and an instrument hierarchy: tools for establishing and
      evaluating the conceptual framework of a patient-reported outcome (PRO)
      instrument as applied to product labeling claims.
AB  - OBJECTIVE: To facilitate development and evaluation of a PRO instrument
      conceptual framework, we propose two tools--a PRO concept taxonomy and a PRO
      instrument hierarchy. FDA's draft guidance on patient reported outcome (PRO)
      measures states that a clear description of the conceptual framework of an
      instrument is useful for evaluating its adequacy to support a treatment benefit
      claim for use in product labeling the draft guidance, however does not propose
      tools for establishing or evaluating a PRO instrument's conceptual framework.
      METHODS: We draw from our review of PRO concepts and instruments that appear in
      prescription drug labeling approved in the United States from 1997 to 2007.
      RESULTS: We propose taxonomy terms that define relationships between PRO
      concepts, including "family,""compound concept," and "singular concept." Based on
      the range of complexity represented by the concepts, as defined by the taxonomy,
      we propose nine instrument orders for PRO measurement. The nine orders range from
      individual event counts to multi-item, multiscale instruments. CONCLUSION: This
      analysis of PRO concepts and instruments illustrates that the taxonomy and
      hierarchy are applicable to PRO concepts across a wide range of therapeutic areas
      and provide a basis for defining the instrument conceptual framework complexity.
      Although the utility of these tools in the drug development, review, and approval
      processes has not yet been demonstrated, these tools could be useful to improve
      communication and enhance efficiency in the instrument development and review
      process.

PMID- 19744290
TI  - On guidelines for comparative effectiveness research using nonrandomized studies
      in secondary data sources.

PMID- 19744291
TI  - The ISPOR Good Practices for Quality Improvement of Cost-Effectiveness Research
      Task Force Report.
AB  - OBJECTIVES: The International Society for Pharmacoeconomics and Outcomes Research
      (ISPOR) Health Science Policy Council recommended and the ISPOR Board of
      Directors approved the formation of a Task Force to critically examine the major
      issues related to Quality Improvement in Cost-effectiveness Research (QICER). The
      Council's primary recommendation for this Task Force was that it should report on
      the quality of cost-effectiveness research and make recommendations to facilitate
      the improvement of pharmacoeconomics and health outcomes research and its use in
      stimulating better health care and policy. Task force members were knowledgeable
      and experienced in medicine, pharmacy, biostatistics, health policy and health
      care decision-making, biomedical knowledge transfer, health economics, and
      pharmacoeconomics. They were drawn from industry, academia, consulting
      organizations, and advisors to governments and came from Japan, the Netherlands,
      Canada and the United States. METHODS: Face-to-face meetings of the Task Force
      were held at ISPOR North American and European meetings and teleconferences
      occurred every few months. Literature reviews and surveys were conducted and the
      first preliminary findings presented at an open forum at the May 2008 ISPOR
      meeting in Toronto. The final draft report was circulated to the expert reviewer
      group and then to the entire membership for comment. The draft report was posted
      on the ISPOR Web site in April 2009. All formal comments received were posted to
      the association Web site and presented for discussion at the Task Force forum
      during the ISPOR 14th Annual International Meeting in May 2009. Comments and
      feedback from the forums, reviewers and membership were considered in the final
      report. Once Task Force consensus was reached, the article was submitted to Value
      in Health. CONCLUSIONS: The QICER Task Force recommends that ISPOR implement the
      following: * With respect to CER guidelines, that ISPOR promote harmonization of
      guidelines, allowing for differences in application, regional needs and politics;
      evaluate available instruments or promote development of a new one that will
      allow standardized quantification of the impact of CER guidelines on the quality
      of CER studies; report periodically on those countries or regions that have
      developed guidelines; periodically evaluate the quality of published studies
      (those journals with CER guidances) or those submitted to decision-making bodies
      (as public transparency increases). * With respect to methodologies, that ISPOR
      promote publication of methodological guidelines in more applied journals in more
      easily understandable format to transfer knowledge to researchers who need to
      apply more rigorous methods; promote full availability of models in electronic
      format to combat space restrictions in hardcopy publications; promote consistency
      of methodological review for all CER studies; promote adoption of explicit best
      practices guidelines among regulatory and reimbursement authorities; periodically
      update all ISPOR Task Force reports; periodically review use of ISPOR Task Force
      guidelines; periodically report on statistical and methodological challenges in
      HE; evaluate periodically whether ISPOR's methodological guidelines lead to
      improved quality; and support training and knowledge transfer of rigorous CER
      methodologies to researchers and health care decision-makers. * With respect to
      publications, that ISPOR develop standard CER guidances to which journals will be
      able to refer their authors and their reviewers; lobby to establish these
      guidances within the International Committee for Medical Journal Editors (ICMJE)
      Requirements to which most journals refer in their Author Instructions; provide
      support in terms of additional reviewer expertise to those journals lacking
      appropriate reviewers; periodically report on journals publishing CER research;
      periodically report on the quality of CER publications; and support training and
      knowledge transfer of the use of these guidelines to researchers and reviewers. *
      With respect to evidence-based health-care decision-making, that ISPOR recognize
      at its annual meetings those countries/agencies/private companies/researchers
      using CER well, and those practitioners and researchers supporting good patient
      use of CER in decision-making; and promote public presentation of case studies of
      applied use of CER concepts or guidelines.

PMID- 19744292
TI  - Good research practices for comparative effectiveness research: approaches to
      mitigate bias and confounding in the design of nonrandomized studies of treatment
      effects using secondary data sources: the International Society for
      Pharmacoeconomics and Outcomes Research Good Research Practices for Retrospective
      Database Analysis Task Force Report--Part II.
AB  - OBJECTIVES: The goal of comparative effectiveness analysis is to examine the
      relationship between two variables, treatment, or exposure and effectiveness or
      outcome. Unlike data obtained through randomized controlled trials, researchers
      face greater challenges with causal inference with observational studies.
      Recognizing these challenges, a task force was formed to develop a guidance
      document on methodological approaches to addresses these biases. METHODS: The
      task force was commissioned and a Chair was selected by the International Society
      for Pharmacoeconomics and Outcomes Research Board of Directors in October 2007.
      This report, the second of three reported in this issue of the Journal, discusses
      the inherent biases when using secondary data sources for comparative
      effectiveness analysis and provides methodological recommendations to help
      mitigate these biases. RESULTS: The task force report provides recommendations
      and tools for researchers to mitigate threats to validity from bias and
      confounding in measurement of exposure and outcome. Recommendations on design of
      study included: the need for data analysis plan with causal diagrams; detailed
      attention to classification bias in definition of exposure and clinical outcome;
      careful and appropriate use of restriction; extreme care to identify and control
      for confounding factors, including time-dependent confounding. CONCLUSIONS:
      Design of nonrandomized studies of comparative effectiveness face several
      daunting issues, including measurement of exposure and outcome challenged by
      misclassification and confounding. Use of causal diagrams and restriction are two
      techniques that can improve the theoretical basis for analyzing treatment effects
      in study populations of more homogeneity, with reduced loss of generalizability.

PMID- 19744293
TI  - Patient characteristics impacting health state index scores, measured by the EQ
      5D of females with stress urinary incontinence symptoms.
AB  - OBJECTIVE: To describe the characteristics of women seeking treatment for
      symptoms of stress urinary incontinence (SUI) and to investigate the association
      of SUI symptoms with generic health-related quality of life (HRQoL) as measured
      by the EuroQol (EQ-5D) instrument. METHODS: The Stress Urinary Incontinence
      Treatment (SUIT) study was a 12-month observational study in four European
      countries that evaluated the cost-effectiveness of duloxetine compared with other
      forms of nonsurgical intervention in the treatment of the symptoms of SUI. Four
      hundred thirty-one physicians observed women seeking treatment for their SUI, and
      recorded the care provided and the outcomes of that care at enrollment and at 3,
      6 and 12 months afterward The impact of SUI on baseline HRQoL as expressed by the
      EQ-5D index score was assessed by linear and logistic regression. RESULTS: Three
      thousand seven hundred sixty-two women were enrolled into SUIT, with the largest
      patient group from Germany. Overall, the majority of women were postmenopausal,
      had a mean age of 58.0 years, were not current smokers, and tended to be
      overweight (mean body mass index [BMI]=27.7 kg/m2), with at least one
      comorbidity. The health state index scores were significantly and independently
      influenced by the presence of comorbidity(ies) affecting quality of life, total
      number of stress and urge incontinence episodes, urinary incontinence subtype,
      comorbidity(ies) affecting incontinence, BMI, socioeconomic status, educational
      status, age, and country. CONCLUSION: This article describes the characteristics
      of patients at the SUIT enrollment visit, and demonstrates that the number of
      incontinence episodes has a significant impact on the EQ-5D index score.

PMID- 19744294
TI  - The impact of pharmaceutical cost containment policies on the range of medicines
      available and subsidized in Finland and New Zealand.
AB  - OBJECTIVE: To identify differences in the range of medicines available and
      subsidized for ambulatory care in Finland and New Zealand. METHODS: Medical
      entities listed in national product information sources and their subsidy
      statuses were compared. The number and overlap of entities available and
      subsidized were determined. Differences in the age of subsidized medicines were
      compared using the date of first registration. Differences in licensing delays
      were compared using a selection of new innovative medicines that provide health
      gain. RESULTS: Within the inclusion criteria, 779/763 entities were available and
      495/471 subsidized in Finland/New Zealand, of which around 30% (30.9% Finland,
      29.5% New Zealand) were not available and approximately 40% (41.4% Finland, 38.4%
      New Zealand) not subsidized in the other country. The proportion of fully
      subsidized entities was higher in New Zealand (86.2%/29.1%). The entities only
      subsidized in New Zealand were significantly older than those only subsidized in
      Finland and the share of licensed and launched innovative medicines was
      significantly smaller in New Zealand. The differences were equally distributed
      across the therapeutic groups but clinically relevant differences were rarely
      found. CONCLUSIONS: In New Zealand, medicines are heavily subsidized across
      therapy groups, but those uniquely subsidized were older entities. In Finland,
      more "newer" medicines are subsidized and available, but the level and coverage
      of subsidy is lower and thus, the patient cost burden is higher. The cost
      containment policies adopted seem to affect patients' access to medicines mainly
      by availability in New Zealand and by affordability in Finland.

PMID- 19744295
TI  - Understanding the medical and nonmedical value of diagnostic testing.
AB  - OBJECTIVES: To develop a framework for defining the potential value of diagnostic
      testing, and discuss its implications for the health-care delivery system.
      METHODS: We reviewed the conceptual and empirical literature related to the
      valuing of diagnostic tests, and used this information to create a framework for
      characterizing their value. We then made inferences about the impact of this
      framework on health insurance coverage, health technology assessment, physician
      patient relationships, and public health policy. RESULTS: Three dimensions can
      effectively classify the potential value created by diagnostic tests: 1) medical
      value (impact on treatment decisions); 2) planning value (affect on patients'
      ability to make better life decisions); and 3) psychic value (how test
      information affects patients' sense of self). This comprehensive framework for
      valuing diagnostics suggests that existing health technology assessments may
      systematically under- or overvalue diagnostics, leading to potentially incorrect
      conclusions about cost-effectiveness. Further, failure to account for all value
      dimensions may lead to distorted payments under a value-based health-care system.
      CONCLUSIONS: The potential value created by medical diagnostics incorporates
      medical value as well as value associated with well-being and planning.
      Consideration of all three dimensions has important implications for technology
      assessment and value-based payment.

PMID- 19744296
TI  - Valuation of EQ-5D health states in Poland: first TTO-based social value set in
      Central and Eastern Europe.
AB  - OBJECTIVE: Currently, there is no EQ-5D value set for Poland. The primary
      objective of this study was to elicit EQ-5D Polish values using the time trade
      off (TTO) method. METHODS: Face-to-face interviews with visitors of inpatients in
      eight medical centers in Warsaw, Skierniewice, and Pulawy were carried out by
      trained interviewers. Quota sampling was used to achieve a representative sample
      of the Polish population with regard to age and sex. Modified protocol from the
      Measurement and Value of Health study was used. Each respondent ranked 10 health
      states and valued 4 health states using the visual analog scale and 23 using the
      TTO. Mean and variance stability tests were performed to determine whether using
      a larger number of health states per respondent would yield credible results.
      Modeling included random effects and random parameters models. RESULTS: Between
      February and May 2008, 321 interviews were performed. Modeling based on 6777
      valuations resulted in an additive model with all coefficients statistically
      significant, R(2) equal to 0.45, and value -0.523 for the worst possible health
      state. Means and variance did not differ significantly for states valued in the
      middle and at the end of the TTO exercise. CONCLUSIONS: This is the first EQ-5D
      value set based on TTO in Central and Eastern Europe so far. Because the values
      differ considerably from those elicited in Western European countries, its use
      should be recommended for studies in Poland. Increasing the number of health
      states that each respondent is asked to value using TTO seems feasible and
      justifiable.

PMID- 19744297
TI  - Using the incremental net benefit framework for quantitative benefit-risk
      analysis in regulatory decision-making--a case study of alosetron in irritable
      bowel syndrome.
AB  - OBJECTIVE: There is consensus that a more transparent, explicit, and rigorous
      approach to benefit-risk evaluation is required. The objective of this study is
      to evaluate the incremental net benefit (INB) framework for undertaking
      quantitative benefit-risk assessment by performing a quantitative benefit-risk
      analysis of alosetron for the treatment of irritable bowel syndrome from the
      patients' perspective. METHODS: A discrete event simulation model was developed
      to determine the INB of alosetron relative to placebo, calculated as "relative
      value-adjusted life-years (RVALYs)." RESULTS: In the base case analysis,
      alosetron resulted in a mean INB of 34.1 RVALYs per 1000 patients treated
      relative to placebo over 52 weeks of treatment. Incorporating parameter
      uncertainty into the model, probabilistic sensitivity analysis revealed a mean
      INB of 30.4 (95% confidence interval 15.9-45.4) RVALYs per 1000 patients treated
      relative to placebo over 52 weeks of treatment. Overall, there was >99% chance
      that both the incremental benefit and incremental risk associated with alosetron
      are greater than placebo. As hypothesized, the INB of alosetron was greatest in
      patients with the worst quality of life experienced at baseline. The mean INB
      associated with alosetron in patients with mild, moderate, and severe symptoms at
      baseline was 17.97 (-0.55 to 36.23), 29.98 (17.05-43.37), and 35.98 (23.49-48.77)
      RVALYs per 1000 patients treated, respectively. CONCLUSIONS: This study
      demonstrates the potential utility of applying the INB framework to real-life
      decision-making, and the ability to use simulation modeling incorporating
      outcomes data from different sources as a benefit-risk decision aid.

PMID- 19744298
TI  - Statistical evaluation of test accuracy studies for Toxoplasma gondii in food
      animal intermediate hosts.
AB  - The availability of accurate diagnostic tests is essential for the detection and
      control of Toxoplasma gondii infections in both definitive and intermediate
      hosts. Sensitivity, specificity and the area under the receiver-operating
      characteristic (ROC) curve are commonly used measures of test accuracy for
      infectious diseases such as toxoplasmosis. These test performance characteristics
      are important considerations when selecting from among a group of tests for a
      specific testing purpose. In this study, we reviewed statistical approaches to
      evaluation of tests for toxoplasmosis with and without a gold-standard
      (reference) test, including use of ROC analysis and likelihood ratios which
      retain the diagnostic information inherent in a quantitative test result. We use
      previously published data from a comparison of the accuracy of serological tests
      for swine toxoplasmosis to demonstrate suggested methods of data analysis. We
      make recommendations for statistical analysis and reporting of test evaluation
      studies for T. gondii in food animals based on our own experiences and those of
      others.

PMID- 19744299
TI  - Radiofrequency-induced thermal inactivation of Toxoplasma gondii oocysts in
      water.
AB  - Toxoplasma gondii, a ubiquitous parasitic protozoan, is emerging as an aquatic
      biological pollutant. Infections can result from drinking water contaminated with
      environmentally resistant oocysts. However, recommendations regarding water
      treatment for oocyst inactivation have not been established. In this study, the
      physical method of radiofrequency (RF) power was evaluated for its ability to
      inactivate T. gondii oocysts in water. Oocysts were exposed to various RF energy
      levels to induce 50, 55, 60, 70 and 80 degrees C temperatures maintained for 1
      min. Post-treatment oocyst viability was determined by mouse bioassay with
      serology, immunohistochemistry and in vitro parasite isolation to confirm T.
      gondii infections in mice. None of the mice inoculated with oocysts treated with
      RF-induced temperatures of > or =60 degrees C in an initial experiment became
      infected; however, there was incomplete oocyst activation in subsequent
      experiments conducted under similar conditions. These results indicate that T.
      gondii oocysts may not always be inactivated when exposed to a minimum of 60
      degrees C for 1 min. The impact of factors such as water heating time, cooling
      time and the volume of water treated must be considered when evaluating the
      efficacy of RF power for oocyst inactivation.

PMID- 19744300
TI  - Infection with Toxoplasma gondii during pregnancy: seroepidemiological studies in
      Austria.
AB  - Seropositivity among pregnant woman in Austria has decreased from 48% to 50% at
      the end of the 1970s to 35% in recent years. Despite this decrease, knowledge of
      possible sources and risk factors for Toxoplasma infection remains important. We
      reviewed seroepidemiological studies that were undertaken to assess the roles of
      undercooked meat and oocysts in cat faeces as potential sources of infection in
      pregnant women. Improved management and hygiene in pig herds raised in
      confinement have resulted in less contact of pigs with cats and a decrease of
      infected pigs within one decade from 14% in 1982 to 0.9% in 1992. In Austrian
      wild boar populations, however, seroprevalences remained essentially unchanged
      during the same decade (18% in 1983 and 19% in 1990-1993). Austrian sheep and
      goats are usually kept on small farms where cats abound and are predominantly
      seropositive (66% in sheep and 69% in goats). The seroprevalence in cats has
      decreased from approximately 81% in 1987 to 59% in 1996; presumably because of
      cats' increased consumption of processed food. Despite the decrease of infection
      in pregnant women via the cat-to-pig pathway, it may be offset by a recent
      concomitant increase in mutton consumption. Free-ranging chickens are a good
      indicator of the prevalence of T. gondii oocysts in the soil because chickens are
      ground feeders. Antibodies to T. gondii, as evaluated by the modified
      agglutination test, were found in 36% of chickens from 12 Austrian 'biofarms'.
      Because Austrians rarely consume raw pork, the fraction of human T. gondii
      infections associated with pig meat consumption is likely small. As meat
      consumption and lifestyle patterns change in Austria, the risk of human infection
      with T. gondii via different pathways needs re-evaluation and targeted
      educational efforts to control transmission.

PMID- 19744301
TI  - What do we know about risk factors for infection in humans with Toxoplasma gondii
      and how can we prevent infections?
AB  - Fourteen case-control studies evaluating the importance of different risk factors
      for infection of humans with Toxoplasma gondii were identified. Surprisingly, up
      to two-thirds of infections could not be explained by risk factors such as
      consuming raw or undercooked meat or poor kitchen hygiene. Few studies reported
      population attributable risk, and when reported, it was low. Protocols including
      questionnaires used for collecting data, age and socio-economic groups studied,
      and sample sizes varied among studies. There is a need for carefully planned,
      case-control studies to identify sources of infection with T. gondii in humans.
      New risk factors, such as the manufacture of organic meat, and possible ways to
      sterilize meat to inactivate T. gondii tissue cysts are discussed.

PMID- 19744302
TI  - Toxoplasmosis prevention and testing in pregnancy, survey of obstetrician
      gynaecologists.
AB  - Toxoplasmosis in pregnant women can lead to congenital disease with severe
      neurological and ocular complications in the foetus. In 2006, we surveyed US
      obstetrician-gynaecologists to determine their knowledge and practices about
      toxoplasmosis prevention and testing. Questionnaires were mailed (four mailings)
      to a random sample of 1200 of the 33,354 members of the American College of
      Obstetricians and Gynecologists (ACOG). Of the 1200 surveyed, 502 (42%)
      responded. The respondents were similar to all ACOG members by gender, region of
      the country and practice type (P > 0.5), and age (respondents were slightly
      younger, mean 46 years versus 47 years). To prevent toxoplasmosis, most
      respondents indicated that they counsel pregnant women about cat litter (99.6%),
      but fewer counselled about eating undercooked meat (77.6%), handling raw meat
      (67.4%), gardening (65.4%) or washing fruits and vegetables (34.2%). Many (73.2%)
      respondents were not aware that some Toxoplasma IgM tests have had a high false
      positive rate, and most (91.2%) had not heard of the avidity test, which can help
      determine the timing of Toxoplasma gondii infection in relation to pregnancy.
      There is a need for more education about T. gondii serological testing,
      particularly the Toxoplasma avidity test. US obstetrician-gynaecologists are
      providing beneficial counselling to their patients, but could provide more
      information about undercooked meat and soil risks.

PMID- 19744303
TI  - A brief history and overview of Toxoplasma gondii.
AB  - Toxoplasma gondii was discovered by scientists working in North Africa and Brazil
      around 100 years ago. The parasite has since been found to be capable of
      infecting all warm-blooded animals including humans making it one of the most
      successful parasitic organisms worldwide. The pathogenic potential of T. gondii
      was recognized in the 1920s and 1930s, in congenitally infected children
      presenting with the classic triad of symptoms, namely hydrocephalus,
      retinochoroiditis and encephalitis. In addition, around the same time T. gondii
      parasites were found to be associated with severe intraocular inflammation. In
      the 1980s, T. gondii emerged as a major cause of death in patients with acquired
      immunodeficiency syndrome, illustrating the importance of the immune system in
      controlling T. gondii infection. T. gondii was reported as a major cause of
      abortion in sheep in New Zealand in the 1950s, which raised questions about
      potential new transmission routes for the parasite. The discovery of the cat as
      the definitive host in the 1960s was a very important finding as it helped to
      complete our understanding of the parasite's life cycle, and the oocyst stage of
      T. gondii shed in the faeces of infected cats was found to be an important source
      of infection for many intermediate hosts and helped to explain infection in
      herbivorous animals and people with a vegetarian diet. In addition, this stage of
      the parasite was very robust and could survive in the environment, depending on
      the climatic conditions, for up to 12-18 months. Knowledge of the parasite's life
      cycle, transmission routes, risk groups and host immune responses has helped in
      the development of strategies to control the disease, reduce transmission of the
      parasite and limit environmental contamination.

PMID- 19744304
TI  - Seroprevalence of and risk factors for Toxoplasma gondii in the US swine herd
      using sera collected during the National Animal Health Monitoring Survey (Swine
      2006).
AB  - The United States Department of Agriculture (USDA) initiated the National Animal
      Health Monitoring System (NAHMS) in 1983 to collect, analyse and disseminate data
      on animal health, management and productivity in US domestic livestock
      populations, including swine. The programme includes an on-farm serological
      sampling component which can be used to monitor seroprevalence of various
      pathogens, including Toxoplasma gondii. The purpose of this study was to
      determine the seroprevalence of T. gondii in grower/finisher pigs using sera
      collected during NAHMS Swine 2006 and to determine farm level factors associated
      with differences in seroprevalence on farms where sera was collected during the
      Swine 2006 survey. Sera and data on management practices for this study were
      collected from 185 grower/finisher swine production sites located in 16 states
      accounting for > 90% of US swine production (Arkansas, Colorado, Iowa, Illinois,
      Indiana, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Carolina, Ohio,
      Pennsylvania, South Dakota, Texas and Wisconsin). A total of 6238 sera were
      tested for T. gondii antibodies using a commercial ELISA assay (Vet.
      Parasitol.128, 2005, 177). Seroprevalence in this study, as determined by ELISA,
      was 2.6%, with a herd prevalence of 21.6% and a mean within-herd prevalence of
      2.7%. Analysis of swine management practices indicated that rodent control
      methods and carcass disposal methods were associated with differences in the
      number of T. gondii positive samples on farm. These results are consistent with
      current epidemiological knowledge of the transmission of Toxoplasma on the farm
      (ingestion of organic matter containing oocysts, or ingestion of infected animal
      tissues). Production practices which eliminate these sources of exposure can
      reduce the risk of Toxoplasma infection in pigs, and reduce the likelihood of
      human infection from consumption of infected pork.

PMID- 19744305
TI  - Toxoplasma gondii infections in chickens (Gallus domesticus): prevalence,
      clinical disease, diagnosis and public health significance.
AB  - Chickens are considered one of the most important hosts in the epidemiology of
      Toxoplasma gondii infection because they are an efficient source of infection for
      cats that excrete the environmentally resistant oocysts and because humans may
      become infected with this parasite after eating undercooked infected chicken
      meat. The objective of this study is to review worldwide prevalence of T. gondii
      infection in chickens and to assess the role of infected chickens in the
      epidemiology of toxoplasmosis in humans. A very high prevalence of the parasite
      was found in chickens raised in backyards (up to 100%) and free-range organic (30
      50%) establishments.

PMID- 19744306
TI  - Cats and Toxoplasma: implications for public health.
AB  - Cats are popular as pets worldwide because they are easy to care for and provide
      companionship that enriches the lives of human beings. Little attention has been
      focused on their potential to contaminate the environment with zoonotic
      pathogens. One such pathogen, the protozoan parasite Toxoplasma gondii, rarely
      causes clinical manifestations in cats or immunocompetent humans; however, it can
      have serious adverse effects on human foetuses and immunocompromised patients.
      Many human infections are believed to be acquired from eating undercooked or raw
      meat, such as pork and lamb (Tenter et al. Int. J. Parasitol., 30, 2000, 1217;
      Dubey et al. J. Parasitol. 91, 2005, 1082). However, the prevalence of T. gondii
      infection in human populations that do not consume meat or eat it well-cooked
      suggests that the acquisition of infection from the environment, via oocysts in
      soil, water or on uncooked vegetables, is also important (Rawal. Trans. Royal
      Soc. Trop. Med. Hyg., 53, 1959, 61; Roghmann et al. Am. J. Trop. Med. Hyg., 60,
      1999, 790; Chacin-Bonilla et al. Am. J. Trop. Med. Hyg., 65, 2001, 131). In the
      past 20 years, two changes occurred that significantly increased the size of the
      cat population in the USA. Pet cat ownership grew from 50 million to 90 million
      animals, and animal welfare activists created feeding stations for abandoned and
      free-roaming cats. As many cat owners allow their cats to deposit faeces outside
      and cats maintained in colonies always defecate outside, ample opportunity exists
      for T. gondii oocysts to enter the environment and be transmitted to humans.
      Prevention efforts should focus on educating cat owners about the importance of
      collecting cat faeces in litter boxes, spaying owned cats to reduce
      overpopulation, reducing the numbers of feral cats and promoting rigorous hand
      hygiene after gardening or soil contact.

PMID- 19744307
TI  - Recent advances in systemic therapy. When HER2 is not the target: advances in the
      treatment of HER2-negative metastatic breast cancer.
AB  - The anti-human epidermal growth factor receptor 2 (HER2) agent trastuzumab has
      improved outcomes in breast cancer patients with HER2 over-expressing tumours.
      However, systemic treatment for patients with HER2-negative disease is still
      limited to endocrine and cytotoxic therapies. The increasing use of the
      anthracyclines and taxanes in early stage disease has reduced the available
      therapeutic options for patients with relapsed disease, and choices are further
      limited for patients with triple-negative tumours, who typically have a poor
      prognosis. The novel agents bevacizumab and ixabepilone were recently approved
      for metastatic breast cancer, and numerous other agents are currently in clinical
      development that may contribute further valuable therapeutic options.

PMID- 19744308
TI  - MicroRNA and vascular smooth muscle cell phenotype: new therapy for
      atherosclerosis?
AB  - MicroRNAs (miRNAs) represent a class of small, non-coding RNAs that negatively
      regulate gene expression via degradation or translational inhibition of their
      target mRNAs. Recent studies have identified that miR-145 is the most abundant
      miRNA in normal arteries and vascular smooth muscle cells (VSMCs), and its
      expression is significantly downregulated in dediffer-entiated VSMCs and
      atherosclerotic arteries. miR-145 plays a critical role in modulating VSMC
      phenotype. Because phenotypic modulation of VSMCs is an initial cellular event in
      the development of atherosclerosis, miRNAs, and miR-145 in particular, may
      represent new therapeutic targets for atherosclerosis.

PMID- 19744309
TI  - Migration and Risk Factors for HIV Acquisition in Pregnant Women in Baja
      California, Mexico.

PMID- 19744310
TI  - Intensive hog farming operations and self-reported health among nearby rural
      residents in Ottawa, Canada.
AB  - BACKGROUND: In 2004, hog farming operations were introduced in the village of
      Sarsfield in the eastern part of Ottawa, Canada. This study evaluates the health
      related quality of life (HRQOL), and the prevalence of respiratory conditions
      among adults and children who lived in proximity to this farm. METHODS: A cross
      sectional survey was administered to a random sample of residents from seven
      rural communities in the eastern part of Ottawa, Canada. We analyzed self
      reported questionnaire data obtained from 723 adults and 285
      children/adolescents. HRQOL was assessed using the SF-36 survey instrument, while
      data were also collected for sociodemographic characteristics, the prevalence of
      selected health conditions, and lifestyle related behaviours (e.g., smoking) of
      participants. Variations in self-reported health according to the residential
      distance to the hog farm were evaluated using logistic regression and analysis of
      variance methods. RESULTS: For the most part, the prevalence of selected health
      conditions among adults and children was not associated with how far they lived
      from the farm. No associations were observed with migraines, respiratory
      conditions (asthma, rhinitis, sinusitis, and chronic bronchitis), and allergies.
      However, a higher prevalence of depression was noted among those who lived within
      3 km of the farm relative to those who lived more than 9 km away (odds ratio =
      2.01, 95% CI = 1.11, 3.65). Furthermore, individuals who lived closer to the IHF
      were more likely to worry about environmental issues such as water quality,
      outdoor and indoor smells, and air pollution. This level of worry also
      contributed to lower HRQOL scores for individuals who lived closer to the farm.
      It was also observed that the prevalence of depression was much higher among
      those who indicated a concern about environmental issues (18.2%) when compared to
      those who did not (8.0%). CONCLUSION: While our findings suggest that living in
      close proximity to an IHF may adversely affect HRQOL these should be interpreted
      cautiously due to a lack of direct measures of environmental exposures, and
      possible biases inherent in the use of self-reported health measures.

PMID- 19744311
TI  - Evaluating Active U: an Internet-mediated physical activity program.
AB  - BACKGROUND: Engaging in regular physical activity can be challenging,
      particularly during the winter months. To promote physical activity at the
      University of Michigan during the winter months, an eight-week Internet-mediated
      program (Active U) was developed providing participants with an online physical
      activity log, goal setting, motivational emails, and optional team participation
      and competition. METHODS: This study is a program evaluation of Active U.
      Approximately 47,000 faculty, staff, and graduate students were invited to
      participate in the online Active U intervention in the winter of 2007.
      Participants were assigned a physical activity goal and were asked to record each
      physical activity episode into the activity log for eight weeks. Statistics for
      program reach, effectiveness, adoption, and implementation were calculated using
      the Re-Aim framework. Multilevel regression analyses were used to assess the
      decline in rates of data entry and goal attainment during the program, to assess
      the likelihood of joining a team by demographic characteristics, to test the
      association between various predictors and the number of weeks an individual met
      his or her goal, and to analyze server load. RESULTS: Overall, 7,483 individuals
      registered with the Active U website ( approximately 16% of eligible), and 79%
      participated in the program by logging valid data at least once. Staff members,
      older participants, and those with a BMI < 25 were more likely to meet their
      weekly physical activity goals, and average rate of meeting goals was higher
      among participants who joined a competitive team compared to those who
      participated individually (IRR = 1.28, P < .001). CONCLUSION: Internet-mediated
      physical activity interventions that focus on physical activity logging and goal
      setting while incorporating team competition may help a significant percentage of
      the target population maintain their physical activity during the winter months.

PMID- 19744312
TI  - Identification of secondary targets of N-containing bisphosphonates in mammalian
      cells via parallel competition analysis of the barcoded yeast deletion
      collection.
AB  - BACKGROUND: Nitrogen-containing bisphosphonates are the elected drugs for the
      treatment of diseases in which excessive bone resorption occurs, for example,
      osteoporosis and cancer-induced bone diseases. The only known target of nitrogen
      containing bisphosphonates is farnesyl pyrophosphate synthase, which ensures
      prenylation of prosurvival proteins, such as Ras. However, it is likely that the
      action of nitrogen-containing bisphosphonates involves additional unknown
      mechanisms. To identify novel targets of nitrogen-containing bisphosphonates, we
      used a genome-wide high-throughput screening in which 5,936 Saccharomyces
      cerevisiae heterozygote barcoded mutants were grown competitively in the presence
      of sub-lethal doses of three nitrogen-containing bisphosphonates (risedronate,
      alendronate and ibandronate). Strains carrying deletions in genes encoding
      potential drug targets show a variation of the intensity of their corresponding
      barcodes on the hybridization array over the time. RESULTS: With this approach,
      we identified novel targets of nitrogen-containing bisphosphonates, such as
      tubulin cofactor B and ASK/DBF4 (Activator of S-phase kinase). The up-regulation
      of tubulin cofactor B may explain some previously unknown effects of nitrogen
      containing bisphosphonates on microtubule dynamics and organization. As nitrogen
      containing bisphosphonates induce extensive DNA damage, we also document the role
      of DBF4 as a key player in nitrogen-containing bisphosphonate-induced
      cytotoxicity, thus explaining the effects on the cell-cycle. CONCLUSIONS: The
      dataset obtained from the yeast screen was validated in a mammalian system,
      allowing the discovery of new biological processes involved in the cellular
      response to nitrogen-containing bisphosphonates and opening up opportunities for
      development of new anticancer drugs.

PMID- 19744313
TI  - Road traffic noise and hypertension: results from a cross-sectional public health
      survey in southern Sweden.
AB  - BACKGROUND: Results from studies of road traffic noise and hypertension are
      heterogeneous with respect to effect size, effects among males and females and
      with respect to effects across age groups. Our objective was to further explore
      these associations. METHODS: The study used cross-sectional public health survey
      data from southern Sweden, including 24,238 adults (18 - 80 years old). We used a
      geographic information system (GIS) to assess the average road noise (LAeq 24 hr)
      at the current residential address. Effects on self-reported hypertension were
      estimated by logistic regression with adjustment for age, sex, BMI, alcohol
      intake, exercise, education, smoking and socioeconomic status. RESULTS: Modest
      exposure effects (OR approximately 1.1) were generally noted in intermediate
      exposure categories (45 -64 dB(A)), and with no obvious trend. The effect was
      more pronounced at > 64 dB(A) (OR 1.45, 95% CI 1.04 - 2.02). Age modified the
      relative effect (p = 0.018). An effect was seen among middle-aged (40 - 59 years
      old) at noise levels 60 - 64 dB(A) (OR = 1.27, 95% CI 1.02 - 1.58)) and at > 64
      dB(A) (OR = 1.91, 95% CI 1.19 - 3.06)). An effect was also indicated among
      younger adults but not among elderly. No apparent effect modification by gender,
      country of origin, disturbed sleep or strained economy was noted. CONCLUSION: The
      study supports an association between road traffic noise at high average levels
      and self-reported hypertension in middle-aged. Future studies should use age
      group -specific relative effect models to account for differences in prevalence.

PMID- 19744314
TI  - Seasonal transmission potential and activity peaks of the new influenza A(H1N1):
      a Monte Carlo likelihood analysis based on human mobility.
AB  - BACKGROUND: On 11 June the World Health Organization officially raised the phase
      of pandemic alert (with regard to the new H1N1 influenza strain) to level 6. As
      of 19 July, 137,232 cases of the H1N1 influenza strain have been officially
      confirmed in 142 different countries, and the pandemic unfolding in the Southern
      hemisphere is now under scrutiny to gain insights about the next winter wave in
      the Northern hemisphere. A major challenge is pre-emptied by the need to estimate
      the transmission potential of the virus and to assess its dependence on
      seasonality aspects in order to be able to use numerical models capable of
      projecting the spatiotemporal pattern of the pandemic. METHODS: In the present
      work, we use a global structured metapopulation model integrating mobility and
      transportation data worldwide. The model considers data on 3,362 subpopulations
      in 220 different countries and individual mobility across them. The model
      generates stochastic realizations of the epidemic evolution worldwide considering
      6 billion individuals, from which we can gather information such as prevalence,
      morbidity, number of secondary cases and number and date of imported cases for
      each subpopulation, all with a time resolution of 1 day. In order to estimate the
      transmission potential and the relevant model parameters we used the data on the
      chronology of the 2009 novel influenza A(H1N1). The method is based on the
      maximum likelihood analysis of the arrival time distribution generated by the
      model in 12 countries seeded by Mexico by using 1 million computationally
      simulated epidemics. An extended chronology including 93 countries worldwide
      seeded before 18 June was used to ascertain the seasonality effects. RESULTS: We
      found the best estimate R0 = 1.75 (95% confidence interval (CI) 1.64 to 1.88) for
      the basic reproductive number. Correlation analysis allows the selection of the
      most probable seasonal behavior based on the observed pattern, leading to the
      identification of plausible scenarios for the future unfolding of the pandemic
      and the estimate of pandemic activity peaks in the different hemispheres. We
      provide estimates for the number of hospitalizations and the attack rate for the
      next wave as well as an extensive sensitivity analysis on the disease parameter
      values. We also studied the effect of systematic therapeutic use of antiviral
      drugs on the epidemic timeline. CONCLUSION: The analysis shows the potential for
      an early epidemic peak occurring in October/November in the Northern hemisphere,
      likely before large-scale vaccination campaigns could be carried out. The
      baseline results refer to a worst-case scenario in which additional mitigation
      policies are not considered. We suggest that the planning of additional
      mitigation policies such as systematic antiviral treatments might be the key to
      delay the activity peak in order to restore the effectiveness of the vaccination
      programs.

PMID- 19744315
TI  - Group versus individual sessions delivered by a physiotherapist for female
      urinary incontinence: an interview study with women attending group sessions
      nested within a randomised controlled trial.
AB  - BACKGROUND: The aim was to explore the concerns and expectations of women invited
      to attend group physiotherapy sessions for the management of female urinary
      incontinence and whether the experience changed their views; and to gather
      recommendations from women attending group sessions on the design and delivery of
      these sessions METHODS: An interview study nested within a randomised controlled
      trial in five British NHS physiotherapy departments, including 22 women who had
      expressed a preference for an individual physiotherapy session but were
      randomised to, and attended, group sessions. RESULTS: Embarrassment was woven
      throughout women's accounts of experiencing urinary incontinence and seeking
      health care. Uncertainty about the nature of group sessions was a source of
      concern. Attending the first session was seen as a big hurdle by many women.
      However, a sense of relief was common once the session started, with most women
      describing some benefit from attendance. Recommendations for design and delivery
      of the sessions from women focused on reducing embarrassment and uncertainty
      prior to attendance. CONCLUSION: Taking account of women's embarrassment and
      providing detailed information about the content of group sessions will enable
      women to benefit from group physiotherapy sessions for the management of female
      urinary incontinence. TRIAL REGISTRATION:  TRIAL REGISTRATION NUMBER: ISRCTN
      16772662.

PMID- 19744316
TI  - Identification of Achaete-scute complex-like 1 (ASCL1) target genes and
      evaluation of DKK1 and TPH1 expression in pancreatic endocrine tumours.
AB  - BACKGROUND: ASCL1 role in pancreatic endocrine tumourigenesis has not been
      established. Recently it was suggested that ASCL1 negatively controls expression
      of the Wnt signalling antagonist DKK1. Notch signalling regulates expression of
      TPH1, the rate limiting enzyme in the biosynthesis of serotonin. Understanding
      the development and proliferation of pancreatic endocrine tumours (PETs) is
      essential for the development of new therapies. METHODS: ASCL1 target genes in
      the pancreatic endocrine tumour cell line BON1 were identified by RNA
      interference and microarray expression analysis. Protein expressions of selected
      target genes in PETs were evaluated by immunohistochemistry. RESULTS: 158
      annotated ASCL1 target genes were identified in BON1 cells, among them DKK1 and
      TPH1 that were negatively regulated by ASCL1. An inverse relation of ASCL1 to
      DKK1 protein expression was observed for 15 out of 22 tumours (68%). Nine tumours
      displayed low ASCL1/high DKK1 and six tumours high ASCL1/low DKK1 expression.
      Remaining PETs showed high ASCL1/high DKK1 (n = 4) or low ASCL1/low DKK1 (n = 3)
      expression. Nine of twelve analysed PETs (75%) showed TPH1 expression with no
      relation to ASCL1. CONCLUSION: A number of genes with potential importance for
      PET tumourigenesis have been identified. ASCL1 negatively regulated the Wnt
      signalling antagonist DKK1, and TPH1 expression in BON1 cells. In concordance
      with these findings DKK1 showed an inverse relation to ASCL1 expression in a
      subset of PETs, which may affect growth control by the Wnt signalling pathway.

PMID- 19744317
TI  - Utility of serial urinary cytology in the initial evaluation of the patient with
      microscopic hematuria.
AB  - BACKGROUND: We determine the utility of serial urinary cytologies in patients
      presenting with microscopic hematuria who were evaluated with upper and lower
      urinary tract studies to rule out a malignancy. METHODS: Two hundred and thirty
      seven patients with the diagnosis of microscopic hematuria were evaluated at an
      inner-city tertiary care hospital. Of these 239 patients, 182 patients had 405
      cytologies obtained as part of their evaluation for hematuria. In addition, all
      patients had their lower urinary tract and upper tract thoroughly evaluated.
      RESULTS: Two hundred and seventy four cytology samples were read as normal, 104
      (26%) as atypia, 7 (2%) as suspicious/malignant, and 20 (5%) as unsatisfactory.
      Seventeen patients (9.3%) had biopsy confirmed bladder cancer. Of these 17
      patients, 2 had normal cytology, 11 had atypia, and 5 had suspicious/malignant.
      No patient had a positive cytology and a negative biopsy. Overall the number of
      hematuric patients harboring bladder cancer was small (7%). Cytology #1 detected
      4 cases of cancer, cytology #2 detected an additional case and cytology #3 did
      not detect any additional cancers. CONCLUSION: Because of this low prevalence of
      bladder cancer in patients presenting with microscopic hematuria and the low
      sensitivity of detecting bladder cancers, the utility of urinary cytology in the
      initial evaluation of patients with hematuria may be minimal. The exact role of
      urinary cytology in the evaluation of hematuria is unknown.

PMID- 19744318
TI  - Commentary: the role of cytologic analysis of voided urine in the work-up of
      asymptomatic microhematuria.
AB  - Microscopic hematuria is a common finding in patients presenting to both primary
      care doctors as well as urologists. Sources of microscopic hematuria include
      infection, stones, inflammatory disorders as well as cancer of the genitourinary
      tract, particularly urothelial cancer. A primary focus in the urologic workup of
      hematuria is to rule out cancer. This is done using radiographic studies as well
      as procedures such as cystoscopy and bladder biopsy. As the authors state in
      their article titled "The utility of serial urinary cytology in the initial
      evaluation of the patient with microscopic hematuria", cytologic analysis of
      voided urine, though attractive due to its noninvasive nature, has been found to
      have the neither the sensitivity, cost-effectiveness, nor the ease of
      administration necessary to replace more invasive diagnostics in the evaluation
      of microscopic hematuria.

PMID- 19744319
TI  - Learning lessons from field surveys in humanitarian contexts: a case study of
      field surveys conducted in North Kivu, DRC 2006-2008.
AB  - Survey estimates of mortality and malnutrition are commonly used to guide
      humanitarian decision-making. Currently, different methods of conducting field
      surveys are the subject of debate among epidemiologists. Beyond the technical
      arguments, decision makers may find it difficult to conceptualize what the
      estimates actually mean. For instance, what makes this particular situation an
      emergency? And how should the operational response be adapted accordingly. This
      brings into question not only the quality of the survey methodology, but also the
      difficulties epidemiologists face in interpreting results and selecting the most
      important information to guide operations. As a case study, we reviewed mortality
      and nutritional surveys conducted in North Kivu, Democratic Republic of Congo
      (DRC) published from January 2006 to January 2009. We performed a PubMed/Medline
      search for published articles and scanned publicly available humanitarian
      databases and clearinghouses for grey literature. To evaluate the surveys, we
      developed minimum reporting criteria based on available guidelines and selected
      peer-review articles. We identified 38 reports through our search strategy; three
      surveys met our inclusion criteria. The surveys varied in methodological quality.
      Reporting against minimum criteria was generally good, but presentation of
      ethical procedures, raw data and survey limitations were missed in all surveys.
      All surveys also failed to consider contextual factors important for data
      interpretation. From this review, we conclude that mechanisms to ensure sound
      survey design and conduct must be implemented by operational organisations to
      improve data quality and reporting. Training in data interpretation would also be
      useful. Novel survey methods should be trialled and prospective data gathering
      (surveillance) employed wherever feasible.

PMID- 19744320
TI  - The mode of lymphoblastoid cell death in response to gas phase cigarette smoke is
      dose-dependent.
AB  - BACKGROUND: Cigarette smoke (CS) is the main cause in the development of chronic
      obstructive pulmonary disease (COPD), the pathogenesis of which is related to an
      extended inflammatory response. In this study, we investigated the effect of low
      and high doses of gas phase cigarette smoke (GPS) on cultured lymphocyte
      progenitor cells, using techniques to assess cell viability and to elucidate
      whether cells die of apoptosis or necrosis upon exposure to different doses of
      GPS. METHODS: In our approach we utilised a newly-established system of exposure
      of cells to GPS that is highly controlled, accurately reproducible and simulates
      CS dosage and kinetics that take place in the smokers' lung. This system was used
      to study the mode of cell death upon exposure to GPS in conjunction with a range
      of techniques widely used for cell death studies such as Annexin V staining,
      activation of caspase -3, cytoplasmic release of cytochrome C, loss of
      mitochondrial membrane potential and DNA fragmentation. RESULTS: Low doses of GPS
      induced specific apoptotic indexes in CCRF-CEM cells. Specifically, cytochrome C
      release and cleaved caspase-3 were detected by immunofluorescence, upon treatment
      with 1-3 puffs GPS. At 4 h post-exposure, caspase-3 activation was observed in
      western blot analysis, showing a decreasing pattern as GPS doses increased.
      Concomitant with this behaviour, a dose-dependent change in Delta psi m
      depolarization was monitored by flow cytometry 2 h post-exposure, while at 4 h
      Delta psi m collapse was observed at the higher doses, indicative of a shift to a
      necrotic demise. A reduction in DNA fragmentation events produced by 5 puffs GPS
      as compared to those provoked by 3 puffs GPS, also pointed towards a necrotic
      response at the higher dose of GPS. CONCLUSION: Collectively, our results support
      that at low doses gas phase cigarette smoke induces apoptosis in cultured T
      lymphocytes, whereas at high doses GPS leads to necrotic death, by-passing the
      characteristic stage of caspase-3 activation and, thus, the apoptotic route.

PMID- 19744321
TI  - Mycoplasma pneumoniae and/or Chlamydophila pneumoniae inoculation causing
      different aggravations in cholesterol-induced atherosclerosis in apoE KO male
      mice.
AB  - BACKGROUND: Chamydophila pneumoniae (CP) and/or Mycoplasma pneumoniae (MP) are
      two bacteria detected in vulnerable atheromas. In this study we aimed to analyze
      whether CP and/or MP aggravates atherosclerosis induced by cholesterol-enriched
      diet in C57BL/6 apoE KO male mice. Thirty male apoE KO mice aged eight weeks fed
      by a diet containing 1% cholesterol until 32 weeks of age were divided into four
      groups: the first was inoculated with CP (n = 7), the second with MP (n = 12),
      the third with both CP + MP (n = 5), and the fourth with saline (sham n = 6). The
      animals were re-inoculated at 36 weeks of age, and sacrificed at 40 weeks of age.
      Two ascending aorta and one aortic arch segments were sampled. In the most
      severely obstructed segment, vessel diameter, plaque height, percentage of
      luminal obstruction and the degree of adventitial inflammation were analyzed. The
      plaque area/intimal surface ratio was obtained by measuring all three segments.
      The adventitial inflammation was semiquantified (0 absent, 1 mild, 2 moderate,
      and 3 diffuse). RESULTS: The mean and standard deviation of plaque height, %
      luminal obstruction, external diameter, the plaque area/intimal surface ratio and
      the adventitial inflammation values are the following for each group: MP (0.20 +/
      0.12 mm, 69 +/- 26%, 0.38 +/- 0.11 mm, 0.04 +/- 0.04 and 0.22 +/- 0.67), CP
      (0.23 +/- 0.08 mm, 90 +/- 26%, 0.37 +/- 0.08 mm, 0.04 +/- 0.03, and 0.44 +/-
      0.53), MP + CP (18 +/- 0.08 mm, 84 +/- 4.0%, 0.35 +/- 0.25 mm, 0.03 +/- 0.03 and
      1.33 +/- 0.82) and sham (0.08 +/- 0.09 mm, 42 +/- 46%, 0.30 +/- 0.10 mm, 0.02 +/-
      0.03 and 0.71 +/- 0.76). A wider area of plaque/intimal surface was observed in
      MP + CP inoculated groups (p = 0.07 and 0.06) as well as an increased plaque
      height in CP (p = 0.01) in comparison with sham group. There was also an
      increased luminal obstruction (p = 0.047) in CP inoculated group in comparison to
      sham group. Adventitial inflammation in MP + CP inoculated group was higher than
      MP, CP and the sham groups (p = 0.02). CONCLUSION: Inoculation of CP, MP or both
      agents in C57BL/6 apoE KO male mice caused aggravation of experimental
      atherosclerosis induced by cholesterol-enriched diet, with distinct
      characteristics. CP inoculation increased the plaque height with positive vessel
      remodeling and co-inoculation of MP + CP caused the highest adventitial
      inflammation measures.

PMID- 19744322
TI  - Tumor tissue levels of Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) and
      outcome following adjuvant chemotherapy in premenopausal lymph node-positive
      breast cancer patients: A retrospective study.
AB  - BACKGROUND: We have previously demonstrated that high tumor tissue levels of TIMP
      1 are associated with no or limited clinical benefit from chemotherapy with CMF
      and anthracyclines in metastatic breast cancer patients. Here, we extend our
      investigations to the adjuvant setting studying outcome after adjuvant
      chemotherapy in premenopausal lymph node-positive patients. We hypothesize that
      TIMP-1 high tumors are less sensitive to chemotherapy and accordingly that high
      tumor tissue levels are associated with shorter survival. METHODS: From our
      original retrospectively collected tumor samples we selected a group of 525 pre
      menopausal lymph node-positive patients (adjuvant treatment: CMF, 324 patients;
      anthracycline-based, 99 patients; no adjuvant chemotherapy, 102 patients). TIMP-1
      levels were measured using ELISA in cytosolic extracts of frozen primary tumors.
      TIMP-1 was analyzed as a continuous variable and as a dichotomized one using the
      median TIMP-1 concentration as a cut point between high and low TIMP-1 groups. We
      analyzed the benefit of adjuvant CMF and anthracyclines in univariate and
      multivariable survival models; endpoints were disease-free (DFS) and overall
      survival (OS). RESULTS: In this selected cohort of high-risk patients, and in the
      subgroup of patients receiving no adjuvant therapy, TIMP-1 was not associated
      with prognosis. In the subgroup of patients treated with anthracyclines, when
      analyzed as a continuous variable we observed a tendency for increasing TIMP-1
      levels to be associated with shorter DFS (multivariable analysis, HR 1.75, 95% CI
      1.00-3.07, P = 0.05) and a significant association between increasing TIMP-1 and
      shorter OS in both univariate (HR 3.52, 95% CI 1.54-8.06, P = 0.003) and
      multivariable analyses (HR 4.19, 95% CI 1.67-10.51, P = 0.002). No statistically
      significant association between TIMP-1 and DFS was observed in the CMF-treated
      patients although high TIMP-1 was associated with shorter OS when analyzed as a
      dichotomized variable (HR 1.64, 95% CI 1.02-2.65, P = 0.04). CONCLUSION: In the
      subgroup of patients receiving adjuvant chemotherapy we found an association
      between shorter survival after treatment in TIMP-1 high patients compared with
      TIMP-1 low patients, especially in patients receiving anthracycline-based
      therapy. This suggests that high tumor tissue levels of TIMP-1 might be
      associated with reduced benefit from classical adjuvant chemotherapy. Our
      findings should be validated in larger prospective studies.

PMID- 19744323
TI  - REFINE (Reducing Falls in In-patient Elderly)--a randomised controlled trial.
AB  - BACKGROUND: Falls in hospitals are common, resulting in injury and anxiety to
      patients, and large costs to NHS organisations. More than half of all in-patient
      falls in elderly people in acute care settings occur at the bedside, during
      transfers or whilst getting up to go to the toilet. In the majority of cases
      these falls are unwitnessed. There is insufficient evidence underpinning the
      effectiveness of interventions to guide clinical staff regarding the reduction of
      falls in the elderly inpatient. New patient monitoring technologies have the
      potential to offer advances in falls prevention. Bedside sensor equipment can
      alert staff, not in the immediate vicinity, to a potential problem and avert a
      fall. However no studies utilizing this assistive technology have demonstrated a
      significant reduction in falls rates in a randomised controlled trial setting.
      METHODS/DESIGN: The research design is an individual patient randomised
      controlled trial of bedside chair and bed pressure sensors, incorporating a radio
      paging alerting mode to alert staff to patients rising from their bed or chair,
      across five acute elderly care wards in Nottingham University Hospitals NHS
      Trust. Participants will be randomised to bedside chair and bed sensors or to
      usual care (without the use of sensors). The primary outcome is the number of
      bedside in-patient falls. DISCUSSION: The REFINE study is the first randomised
      controlled trial of bedside pressure sensors in elderly inpatients in an acute
      NHS Trust. We will assess whether falls can be successfully and cost effectively
      reduced using this technology, and report on its acceptability to both patients
      and staff.

PMID- 19744324
TI  - Evolutionary history of selenocysteine incorporation from the perspective of
      SECIS binding proteins.
AB  - BACKGROUND: The co-translational incorporation of selenocysteine into nascent
      polypeptides by recoding the UGA stop codon occurs in all domains of life. In
      eukaryotes, this event requires at least three specific factors: SECIS binding
      protein 2 (SBP2), a specific translation elongation factor (eEFSec),
      selenocysteinyl tRNA, and a cis-acting selenocysteine insertion sequence (SECIS)
      element in selenoprotein mRNAs. While the phylogenetic relationships of
      selenoprotein families and the evolution of selenocysteine usage are well
      documented, the evolutionary history of SECIS binding proteins has not been
      explored. RESULTS: In this report we present a phylogeny of the eukaryotic SECIS
      binding protein family which includes SBP2 and a related protein we herein term
      SBP2L. Here we show that SBP2L is an SBP2 paralogue in vertebrates and is the
      only form of SECIS binding protein in invertebrate deuterostomes, suggesting a
      key role in Sec incorporation in these organisms, but an SBP2/SBP2L fusion
      protein is unable to support Sec incorporation in vitro. An in-depth phylogenetic
      analysis of the conserved L7Ae RNA binding domain suggests an ancestral
      relationship with ribosomal protein L30. In addition, we describe the emergence
      of a motif upstream of the SBP2 RNA binding domain that shares significant
      similarity with a motif within the pseudouridine synthase Cbf5. CONCLUSION: Our
      analysis suggests that SECIS binding proteins arose once in evolution but
      diverged significantly in multiple lineages. In addition, likely due to a gene
      duplication event in the early vertebrate lineage, SBP2 and SBP2L are paralogous
      in vertebrates.

PMID- 19744325
TI  - Comparative EST transcript profiling of peach fruits under different post-harvest
      conditions reveals candidate genes associated with peach fruit quality.
AB  - BACKGROUND: Cold storage is used to inhibit peach fruit ripening during shipment
      to distant markets. However, this cold storage can negatively affect the quality
      of the fruit when it is ripened, resulting in disorders such as wooliness,
      browning or leathering. In order to understand the individual and combined
      biological effects that factors such as cold storage and ripening have on the
      fruit and fruit quality, we have taken a comparative EST transcript profiling
      approach to identify genes that are differentially expressed in response to these
      factors. RESULTS: We sequenced 50,625 Expressed Sequence Tags (ESTs) from peach
      mesocarp (Prunus persica O'Henry variety) stored at four different postharvest
      conditions. A total of 10,830 Unigenes (4,169 contigs and 6,661 singletons) were
      formed by assembling these ESTs. Additionally, a collection of 614 full-length
      and 1,109 putative full-length cDNA clones within flanking loxP recombination
      sites was created. Statistically analyzing the EST population, we have identified
      genes that are differentially expressed during ripening, in response to cold
      storage or the combined effects of cold storage and ripening. Pair-wise
      comparisons revealed 197 contigs with at least one significant difference in
      transcript abundance between at least two conditions. Gene expression profile
      analyses revealed that the contigs may be classified into 13 different clusters
      of gene expression patterns. These clusters include groups of contigs that
      increase or decrease transcript abundance during ripening, in response to cold or
      ripening plus cold. CONCLUSION: These analyses have enabled us to statistically
      identify novel genes and gene clusters that are differentially expressed in
      response to post-harvest factors such as long-term cold storage, ripening or a
      combination of these two factors. These differentially expressed genes reveal the
      complex biological processes that are associated with these factors, as well as a
      large number of putative gene families that may participate differentially in
      these processes. In particular, these analyzes suggest that woolly fruits lack
      the increased boost of metabolic processes necessary for ripening. Additionally,
      these results suggest that the mitochondria and plastids play a major role in
      these processes. The EST sequences and full-length cDNA clones developed in this
      work, combined with the large population of differentially expressed genes may
      serve as useful tools and markers that will enable the scientific community to
      better define the molecular processes that affect fruit quality in response to
      post-harvest conditions and the organelles that participate in these processes.

PMID- 19744326
TI  - Acculturation and use of health care services by Turkish and Moroccan migrants: a
      cross-sectional population-based study.
AB  - BACKGROUND: There is insufficient empirical evidence which shows if and how there
      is an interrelation between acculturation and health care utilisation. The
      present study seeks to establish this evidence within first generation Turkish
      and Moroccan migrants, two of the largest migrant groups in present-day Western
      Europe. METHODS: Data were derived from the Amsterdam Health Monitor 2004, and
      were complete for 358 Turkish and 288 Moroccan foreign-born migrants. Use of
      health services (general practitioner, outpatient specialist and health care for
      mental health problems) was measured by means of self-report. Acculturation was
      measured by a structured questionnaire grading (i) ethnic self-identification,
      (ii) social interaction with ethnic Dutch, (iii) communication in Dutch within
      one's private social network, (iv) emancipation, and (v) cultural orientation
      towards the public domain. RESULTS: Acculturation was hardly associated with the
      use of general practitioner care. However, in case of higher adaptation to the
      host culture there was less uptake of outpatient specialist care among Turkish
      respondents (odds ratio [OR] = 0.90, 95% confidence interval [CI] = 0.82-0.99)
      and Moroccan male respondents (OR = 0.81, 95% CI = 0.71-0.93). Conversely, there
      was a higher uptake of mental health care among Turkish men (OR = 0.81, 95% CI =
      0.71-0.93) and women (OR = 0.81, 95% CI = 0.71-0.93). Uptake of mental health
      care among Moroccan respondents again appeared lower (OR = 0.74, 95% CI = 0.55
      0.99). Language ability appeared to play a central role in the uptake of health
      care. CONCLUSION: Some results were in accordance with the popular view that an
      increased participation in the host society is concomitant to an increased use of
      health services. However, there was heterogeneity across ethnic and gender
      groups, and across the domains of acculturation. Language ability appeared to
      play a central role. Further research needs to explore this heterogeneity into
      more detail. Also, other cultural and/or contextual aspects that influence the
      use of health services require further identification.

PMID- 19744327
TI  - Teaching trainers to incorporate evidence-based medicine (EBM) teaching in
      clinical practice: the EU-EBM project.
AB  - BACKGROUND: Evidence based medicine (EBM) is considered an integral part of
      medical training, but integration of teaching various EBM steps in everyday
      clinical practice is uncommon. Currently EBM is predominantly taught through
      theoretical courses, workshops and e-learning. However, clinical teachers lack
      confidence in teaching EBM in workplace and are often unsure of the existing
      opportunities for teaching EBM in the clinical setting. There is a need for
      continuing professional development (CPD) courses that train clinical trainers to
      teach EBM through on-the-job training by demonstration of applied EBM real time
      in clinical practice. We developed such a course to encourage clinically relevant
      teaching of EBM in post-graduate education in various clinical environments.
      METHODS: We devised an e-learning course targeting trainers with EBM knowledge to
      impart educational methods needed to teach application of EBM teaching in
      commonly used clinical settings. The curriculum development group comprised
      experienced EBM teachers, clinical epidemiologists, clinicians and
      educationalists from institutions in seven European countries. The e-learning
      sessions were designed to allow participants (teachers) to undertake the course
      in the workplace during short breaks within clinical activities. An independent
      European steering committee provided input into the process. RESULTS: The
      curriculum defined specific learning objectives for teaching EBM by exploiting
      educational opportunities in six different clinical settings. The e-modules
      incorporated video clips that demonstrate practical and effective methods of EBM
      teaching in everyday clinical practice. The course encouraged focussed teaching
      activities embedded within a trainer's personal learning plan and documentation
      in a CPD portfolio for reflection. CONCLUSION: This curriculum will help senior
      clinicians to identify and make the best use of available opportunities in
      everyday practice in clinical situations to teach various steps of EBM and
      demonstrate their applicability to clinical practice. Once fully implemented, the
      ultimate outcome of this pilot project will be a European qualification in
      teaching EBM, which will be used by doctors, hospitals, professional bodies
      responsible for postgraduate qualifications and continuing medical education.

PMID- 19744328
TI  - Individual and contextual covariates of burnout: a cross-sectional nationwide
      study of French teachers.
AB  - BACKGROUND: Limited information on the covariates of burnout syndrome in French
      teachers is available. The aim of this study was to evaluate the relative
      contributions of individual and contextual factors on the three burnout
      dimensions: emotional exhaustion, depersonalization, and reduced personal
      accomplishment. METHODS: The source data come from an epidemiological postal
      survey on physical and mental health conducted in 2005 among 20,099 education
      workers (in activity or retired) selected at random from the health plan records
      of the national education system. The response rate was 52.4%. Teachers in
      activity currently giving classes to students who participated in the survey (n =
      3,940) were invited to complete a self-administered questionnaire including the
      Maslach Burnout Inventory. 2,558 teachers provided complete data (64.9%).
      Variables associated with high emotional exhaustion (highest quartile of score),
      high depersonalization (highest quartile), and reduced personal accomplishment
      (lowest quartile) were evaluated using multivariate logistic regression. Studied
      variables referred to demographic characteristics, socio-professional
      environment, job dissatisfaction, experienced difficulties at work, and teaching
      motivations. RESULTS: Different variables were associated with each burnout
      dimension. Female teachers were more susceptible to high emotional exhaustion and
      reduced personal accomplishment, whereas male teachers were more susceptible to
      high depersonalization. Elementary school teachers were more susceptible to high
      emotional exhaustion, but less susceptible to high depersonalization and reduced
      personal accomplishment than their higher school level counterparts. Experienced
      difficulties with pupils were associated with all three dimensions. A socio
      economically underprivileged school neighbourhood was also related to high
      emotional exhaustion and high depersonalization. CONCLUSION: Programs to enhance
      teaching environment might be an interesting approach to try to prevent burnout.
      It would be useful to take the different dimensions into account in planning the
      intervention.

PMID- 19744329
TI  - Nuclear receptor complement of the cnidarian Nematostella vectensis: phylogenetic
      relationships and developmental expression patterns.
AB  - BACKGROUND: Nuclear receptors are a superfamily of metazoan transcription factors
      that regulate diverse developmental and physiological processes. Sequenced
      genomes from an increasing number of bilaterians have provided a more complete
      picture of duplication and loss of nuclear receptors in protostomes and
      deuterostomes but have left open the question of which nuclear receptors were
      present in the cnidarian-bilaterian ancestor. In addition, nuclear receptor
      expression and function are largely uncharacterized within cnidarians, preventing
      determination of conserved and novel nuclear receptor functions in the context of
      animal evolution. RESULTS: Here we report the first complete set of nuclear
      receptors from a cnidarian, the starlet sea anemone Nematostella vectensis.
      Genomic searches using conserved DNA- and ligand-binding domains revealed
      seventeen nuclear receptors in N. vectensis. Phylogenetic analyses support N.
      vectensis orthologs of bilaterian nuclear receptors in four nuclear receptor
      subfamilies within nuclear receptor family 2 (COUP-TF, TLL, HNF4, TR2/4) and one
      putative ortholog of GCNF (nuclear receptor family 6). Other N. vectensis genes
      grouped well with nuclear receptor family 2 but represented lineage-specific
      duplications somewhere within the cnidarian lineage and were not clear orthologs
      of bilaterian genes. Three nuclear receptors were not well-supported within any
      particular nuclear receptor family. The seventeen nuclear receptors exhibited
      distinct developmental expression patterns, with expression of several nuclear
      receptors limited to a subset of developmental stages. CONCLUSION: N. vectensis
      contains a diverse complement of nuclear receptors including orthologs of several
      bilaterian nuclear receptors. Novel nuclear receptors in N. vectensis may be
      ancient genes lost from triploblastic lineages or may represent cnidarian
      specific radiations. Nuclear receptors exhibited distinct developmental
      expression patterns, which are consistent with diverse regulatory roles for these
      genes. Understanding the evolutionary relationships and developmental expression
      of the N. vectensis nuclear receptor complement provides insight into the
      evolution of the nuclear receptor superfamily and a foundation for mechanistic
      characterization of cnidarian nuclear receptor function.

PMID- 19744330
TI  - Improvement of the clinical applicability of the Genomic Grade Index through a
      qRT-PCR test performed on frozen and formalin-fixed paraffin-embedded tissues.
AB  - BACKGROUND: Proliferation and tumor differentiation captured by the genomic grade
      index (GGI) are important prognostic indicators in breast cancer (BC) especially
      for the estrogen receptor positive (ER+) disease. The aims of this study were to
      convert this microarray index to a qRT-PCR assay (PCR-GGI), which could be
      realized on formalin fixed paraffin embedded samples (FFPE), and to assess its
      prognostic performance and predictive value of clinical benefit in early and
      advanced ER+ BC patients treated with tamoxifen. METHODS: The accuracy and
      concordance of the PCR-GGI with the GGI was assessed using BC patients for which
      frozen and FFPE tissues as well as microarray data were available (n = 19). The
      evaluation of the prognostic value of the PCR-GGI was assessed on FFPE material
      using a consecutive series of 212 systemically treated early BC patients. The
      predictive performance for tamoxifen benefit was assessed using two ER+ BC
      populations treated either with adjuvant tamoxifen only (n = 77+139) or first
      line tamoxifen for advanced disease (n = 270). RESULTS: The PCR-GGI is based on
      the expression of 8 genes (4 representative of the GGI and 4 reference genes). A
      significant correlation was observed between the microarray-derived GGI and the
      qRT-PCR assay using frozen (rho = 0.95, p < 10E-06) and FFPE material (rho =
      0.89, p < 10E-06). The prognostic performance of the PCR-GGI was confirmed on
      FFPE samples (HRunivar. = 1.89; [95CI:1.01-3.54], p = 0.05). The PCR-GGI further
      identified two subgroups of patients with statistically different time to distant
      metastasis free survival (DMFS) across the two cohorts of ER+ BC patients treated
      with adjuvant tamoxifen. Additionally, the PCR-GGI was associated with response
      to tamoxifen in the advanced setting (HRunivar. = 1.98; [95CI:1.51-2.59], p =
      6.9E-07). CONCLUSION: PCR-GGI recapitulates in an accurate and reproducible
      manner the performances of the GGI using frozen and FFPE samples.

PMID- 19744331
TI  - Structural effects of clinically observed mutations in JAK2 exons 13-15:
      comparison with V617F and exon 12 mutations.
AB  - BACKGROUND: The functional relevance of many of the recently detected JAK2
      mutations, except V617F and exon 12 mutants, in patients with chronic
      myeloproliferative neoplasia (MPN) has been significantly overlooked. To explore
      atomic-level explanations of the possible mutational effects from those
      overlooked mutants, we performed a set of molecular dynamics simulations on
      clinically observed mutants, including newly discovered mutations (K539L, R564L,
      L579F, H587N, S591L, H606Q, V617I, V617F, C618R, L624P, whole exon 14-deletion)
      and control mutants (V617C, V617Y, K603Q/N667K). RESULTS: Simulation results are
      consistent with all currently available clinical/experimental evidence. The
      simulation-derived putative interface, not possibly obtained from static models,
      between the kinase (JH1) and pseudokinase (JH2) domains of JAK2 provides a
      platform able to explain the mutational effect for all mutants, including
      presumably benign control mutants, at the atomic level. CONCLUSION: The results
      and analysis provide structural bases for mutational mechanisms of JAK2, may
      advance the understanding of JAK2 auto-regulation, and have the potential to lead
      to therapeutic approaches. Together with recent mutation profiling results
      demonstrating the breadth of clinically observed JAK2 mutations, our findings
      suggest that molecular testing/diagnostics of JAK2 should extend beyond V617F and
      exon 12 mutations, and perhaps should encompass most of the pseudo-kinase domain
      coding region.

PMID- 19744332
TI  - A novel nonparametric approach for estimating cut-offs in continuous risk
      indicators with application to diabetes epidemiology.
AB  - BACKGROUND: Epidemiological and clinical studies, often including anthropometric
      measures, have established obesity as a major risk factor for the development of
      type 2 diabetes. Appropriate cut-off values for anthropometric parameters are
      necessary for prediction or decision purposes. The cut-off corresponding to the
      Youden-Index is often applied in epidemiology and biomedical literature for
      dichotomizing a continuous risk indicator. METHODS: Using data from a
      representative large multistage longitudinal epidemiological study in a primary
      care setting in Germany, this paper explores a novel approach for estimating
      optimal cut-offs of anthropomorphic parameters for predicting type 2 diabetes
      based on a discontinuity of a regression function in a nonparametric regression
      framework. RESULTS: The resulting cut-off corresponded to values obtained by the
      Youden Index (maximum of the sum of sensitivity and specificity, minus one),
      often considered the optimal cut-off in epidemiological and biomedical research.
      The nonparametric regression based estimator was compared to results obtained by
      the established methods of the Receiver Operating Characteristic plot in various
      simulation scenarios and based on bias and root mean square error, yielded
      excellent finite sample properties. CONCLUSION: It is thus recommended that this
      nonparametric regression approach be considered as valuable alternative when a
      continuous indicator has to be dichotomized at the Youden Index for prediction or
      decision purposes.

PMID- 19744333
TI  - Gene expression profiling of human alveolar macrophages infected by B. anthracis
      spores demonstrates TNF-alpha and NF-kappab are key components of the innate
      immune response to the pathogen.
AB  - BACKGROUND: Bacillus anthracis, the etiologic agent of anthrax, has recently been
      used as an agent of bioterrorism. The innate immune system initially appears to
      contain the pathogen at the site of entry. Because the human alveolar macrophage
      (HAM) plays a key role in lung innate immune responses, studying the HAM response
      to B. anthracis is important in understanding the pathogenesis of the pulmonary
      form of this disease. METHODS: In this paper, the transcriptional profile of B.
      anthracis spore-treated HAM was compared with that of mock-infected cells, and
      differentially expressed genes were identified by Affymetrix microarray analysis.
      A portion of the results were verified by Luminex protein analysis. RESULTS: The
      majority of genes modulated by spores were upregulated, and a lesser number were
      downregulated. The differentially expressed genes were subjected to Ingenuity
      Pathway analysis, the Database for Annotation, Visualization and Integrated
      Discovery (DAVID) analysis, the Promoter Analysis and Interaction Network Toolset
      (PAINT) and Oncomine analysis. Among the upregulated genes, we identified a group
      of chemokine ligand, apoptosis, and, interestingly, keratin filament genes.
      Central hubs regulating the activated genes were TNF-alpha, NF-kappaB and their
      ligands/receptors. In addition to TNF-alpha, a broad range of cytokines was
      induced, and this was confirmed at the level of translation by Luminex multiplex
      protein analysis. PAINT analysis revealed that many of the genes affected by
      spores contain the binding site for c-Rel, a member of the NF-kappaB family of
      transcription factors. Other transcription regulatory elements contained in many
      of the upregulated genes were c-Myb, CP2, Barbie Box, E2F and CRE-BP1. However,
      many of the genes are poorly annotated, indicating that they represent novel
      functions. Four of the genes most highly regulated by spores have only previously
      been associated with head and neck and lung carcinomas. CONCLUSION: The results
      demonstrate not only that TNF-alpha and NF-kappab are key components of the
      innate immune response to the pathogen, but also that a large part of the
      mechanisms by which the alveolar macrophage responds to B. anthracis are still
      unknown as many of the genes involved are poorly annotated.

PMID- 19744334
TI  - Comprehensive molecular etiology analysis of nonsyndromic hearing impairment from
      typical areas in China.
AB  - BACKGROUND: Every year, 30,000 babies are born with congenital hearing impairment
      in China. The molecular etiology of hearing impairment in the Chinese population
      has not been investigated thoroughly. To provide appropriate genetic testing and
      counseling to families, we performed a comprehensive investigation of the
      molecular etiology of nonsyndromic deafness in two typical areas from northern
      and southern China. METHODS: A total of 284 unrelated school children with
      hearing loss who attended special education schools in China were enrolled in
      this study, 134 from Chifeng City in Inner Mongolia and the remaining 150 from
      Nangtong City in JiangSu Province. Screening was performed for GJB2, GJB3, GJB6,
      SLC26A4, 12S rRNA, and tRNAser(UCN) genes in this population. All patients with
      SLC26A4 mutations or variants were subjected to high-resolution temporal bone CT
      scan to verify the enlarged vestibular aqueduct. RESULTS: Mutations in the GJB2
      gene accounted for 18.31% of the patients with nonsyndromic hearing loss, 1555A>G
      mutation in mitochondrial DNA accounted for 1.76%, and SLC26A4 mutations
      accounted for 13.73%. Almost 50% of the patients with nonsyndromic hearing loss
      in these typical Chinese areas carried GJB2 or SLC26A4 mutations. No significant
      differences in mutation spectrum or prevalence of GJB2 and SLC26A4 were found
      between the two areas. CONCLUSION: In this Chinese population, 54.93% of cases
      with hearing loss were related to genetic factors. The GJB2 gene accounted for
      the etiology in about 18.31% of the patients with hearing loss, SLC26A4 accounted
      for about 13.73%, and mtDNA 1555A>G mutation accounted for 1.76%. Mutations in
      GJB3, GJB6, and mtDNA tRNAser(UCN) were not common in this Chinese cohort.
      Conventionally, screening is performed for GJB2, SLC26A4, and mitochondrial 12S
      rRNA in the Chinese deaf population.

PMID- 19744335
TI  - Incidence and risk factors of hospitalization for bronchiolitis in preterm
      children: a retrospective longitudinal study in Italy.
AB  - BACKGROUND: Bronchiolitis is a distressing, potentially life-threatening
      respiratory condition that affects infants. We evaluated the incidence and risk
      factors of hospitalization for broncholitis in preterm infants (i.e., a
      gestational age of <36 weeks) born between 2000 and 2006, and the use and impact
      of Palivizumab, a monoclonal antibody that in randomized clinical trials has been
      shown to lessen the severity of RSV-related bronchiolitis. METHODS: Retrospective
      cohort study that linked data from four health administrative databases in the
      Lazio region (a region of central Italy): the birth register, the hospital
      discharge register, and two ad-hoc databases that record the doses of Palivizumab
      administered at two local health units. RESULTS: Among 2407 preterm infants, 137
      had at least one hospitalization for bronchiolitis in the first 18 months of
      life, an overall incidence rate of 4.70 per 100 person-years (95%CI: 3.98-5.56);
      similar incidence rates were observed by calendar year. A multiple Poisson model
      showed that the following characteristics were associated with higher incidence:
      younger age of the infant, the period between October-April, male gender, low
      Apgar score at birth, low birth weight, and low maternal educational level. At
      least one dose of Palivizumab was administered to 324 (13.5%) children; a
      dramatic increase from 2000 (2.8%) to 2006 (19.1%) (p < 0.01) was observed. Other
      factors independently associated with more frequent Palivizumab use were older
      maternal age, Italian-born mothers, female gender, low Apgar score, low birth
      weight, shorter gestational age, a diagnosis of broncho-dysplasia, and the month
      of birth. It is of note that none of the 34 children with congenital heart
      disease were prescribed Palivizumab. Performing several multiple Poisson models
      that also considered Palivizumab use as covariate, although the point estimates
      were in agreement with previous clinical trial results, we did not find in most
      of them a significant reduction for immunized children to be hospitalized for
      bronchiolitis. CONCLUSION: In Italy the incidence of hospitalization for
      bronchiolitis, and its associated risk factors, are similar to that found in
      other countries. Although Palivizumab use is associated with the most important
      characteristics of severe prematurity, other aspects of its non-use in children
      with congenital heart disease, the age and the birth country of the mother
      suggest the need for public health measures that can reduce these health
      disparities. Finally, the estimated effectiveness of Palivizumab in routine
      practice, although not significant, confirms the results of previous clinical
      trials, but its impact on modifying the temporal trend in this population is
      still negligible.

PMID- 19744336
TI  - A systematic review of the diagnostic accuracy of prostate specific antigen.
AB  - BACKGROUND: Prostate cancer is the fourth commonest cancer in the UK, and the
      incidence is rising. The reference standard for diagnosing this condition is
      prostate biopsy, an invasive procedure. This study systematically reviews recent
      literature on tPSA accuracy. The time period was restricted to ensure that the
      estimates referred to contemporary tPSA tests and prostate cancer reference
      standards. The focus of this review was restricted to European populations as
      tPSA levels are known to vary by population group. METHODS: Medline was searched
      (from 01/1998 to 01/2008) and Embase (from 01/1998 to 01/2008), which returned
      3087 citations. These were assessed by 6 reviewers, who shortlisted 54 of
      possible relevance. 2 reviewers assessed each using the following inclusion
      criteria: data collection between 1998-2008; tPSA measurements for all
      participants; histological confirmation of the diagnosis; samples from a European
      population and sufficient data to calculate 2 x 2 tables. The final set of 10
      included studies represented 5373 participants. Quality of the included studies
      was assessed in duplicate using criteria suggested by the Cochrane Collaboration.
      Review Manager 5.0 software was used to analyse the data, including plotting a
      series of summary receiver operator curve spaces (SROC). RESULTS: tPSA
      sensitivities ranged from 0.78 to 1.00 and specificities from 0.06 to 0.66.
      Positive likelihood ratios ranged from 0.83 to 2.90 and negative likelihood
      ratios ranged from 0.00 to 3.75 CONCLUSION: tPSA has a role to play as one of
      several indicators for prostate biopsy along with abnormal digital rectal
      examination and urinary symptoms. However, tPSA test has a high false positive
      and significant false negative rate. It is important that clinicians understand
      these limitations.

PMID- 19744337
TI  - Cysteine protease activation and apoptosis in Murine norovirus infection.
AB  - BACKGROUND: Noroviruses are the leading cause of viral gastroenteritis. Because a
      suitable in vitro culture system for the human virus has yet to be developed,
      many basic details of the infection process are unknown. Murine norovirus (MNV)
      serves as a model system for the study of norovirus infection. Recently it was
      shown that infection of RAW 264.7 cells involved a novel apoptotic pathway
      involving survivin. RESULTS: Using a different set of approaches, the up
      regulation of caspases, DNA condensation/fragmentation, and membrane blebbing,
      all of which are markers of apoptosis, were confirmed. Live cell imaging and
      activity-based protein profiling showed that activation of caspase-like proteases
      occurred within two hours of infection, followed by morphological changes to the
      cells. MNV infection in the presence of caspase inhibitors proceeded via a
      distinct pathway of rapid cellular necrosis and reduced viral production.
      Affinity purification of activity-based protein profiling targets and
      identification by peptide mass fingerprinting showed that the cysteine protease
      cathepsin B was activated early in infection, establishing this protein as an
      upstream activator of the intrinsic apoptotic pathway. CONCLUSION: This work adds
      cathepsin B to the noncanonical programmed cell death induced by MNV, and
      provides data suggesting that the virus may induce apoptosis to expand the window
      of time for viral replication. This work also highlights the significant power of
      activity-based protein profiling in the study of viral pathogenesis.

PMID- 19744338
TI  - Covariate balance in a Bayesian propensity score analysis of beta blocker therapy
      in heart failure patients.
AB  - Regression adjustment for the propensity score is a statistical method that
      reduces confounding from measured variables in observational data. A Bayesian
      propensity score analysis extends this idea by using simultaneous estimation of
      the propensity scores and the treatment effect. In this article, we conduct an
      empirical investigation of the performance of Bayesian propensity scores in the
      context of an observational study of the effectiveness of beta-blocker therapy in
      heart failure patients. We study the balancing properties of the estimated
      propensity scores. Traditional Frequentist propensity scores focus attention on
      balancing covariates that are strongly associated with treatment. In contrast, we
      demonstrate that Bayesian propensity scores can be used to balance the
      association between covariates and the outcome. This balancing property has the
      effect of reducing confounding bias because it reduces the degree to which
      covariates are outcome risk factors.

PMID- 19744339
TI  - A before-after implementation trial of smoking cessation guidelines in
      hospitalized veterans.
AB  - BACKGROUND: Although most hospitalized smokers receive some form of cessation
      counseling during hospitalization, few receive outpatient cessation counseling
      and/or pharmacotherapy following discharge, which are key factors associated with
      long-term cessation. US Department of Veterans Affairs (VA) hospitals are
      challenged to find resources to implement and maintain the kind of high intensity
      cessation programs that have been shown to be effective in research studies. Few
      studies have applied the Chronic Care Model (CCM) to improve inpatient smoking
      cessation. SPECIFIC OBJECTIVES: The primary objective of this protocol is to
      determine the effect of a nurse-initiated intervention, which couples low
      intensity inpatient counseling with sustained proactive telephone counseling, on
      smoking abstinence in hospitalized patients. Key secondary aims are to determine
      the impact of the intervention on staff nurses' attitudes toward providing
      smoking cessation counseling; to identify barriers and facilitators to
      implementation of smoking cessation guidelines in VA hospitals; and to determine
      the short-term cost-effectiveness of implementing the intervention. DESIGN: Pre
      post study design in four VA hospitals. PARTICIPANTS: Hospitalized patients, aged
      18 or older, who smoke at least one cigarette per day. INTERVENTION: The
      intervention will include: nurse training in delivery of bedside cessation
      counseling, electronic medical record tools (to streamline nursing assessment and
      documentation, to facilitate prescription of pharmacotherapy), computerized
      referral of motivated inpatients for proactive telephone counseling, and use of
      internal nursing facilitators to provide coaching to staff nurses practicing in
      non-critical care inpatient units. OUTCOMES: The primary endpoint is seven-day
      point prevalence abstinence at six months following hospital admission and
      prolonged abstinence after a one-month grace period. To compare abstinence rates
      during the intervention and baseline periods, we will use random effects logistic
      regression models, which take the clustered nature of the data within nurses and
      hospitals into account. We will assess attitudes of staff nurses toward cessation
      counseling by questionnaire and will identify barriers and facilitators to
      implementation by using clinician focus groups. To determine the short-term
      incremental cost per quitter from the perspective of the VA health care system,
      we will calculate cessation-related costs incurred during the initial
      hospitalization and six-month follow-up period. TRIAL NUMBER: NCT00816036.

PMID- 19744340
TI  - Glucocorticoids with different chemical structures but similar glucocorticoid
      receptor potency regulate subsets of common and unique genes in human trabecular
      meshwork cells.
AB  - BACKGROUND: In addition to their well-documented ocular therapeutic effects,
      glucocorticoids (GCs) can cause sight-threatening side-effects including ocular
      hypertension presumably via morphological and biochemical changes in trabecular
      meshwork (TM) cells. In the present study, we directly compared the
      glucocorticoid receptor (GR) potency for dexamethasone (DEX), fluocinolone
      acetonide (FA) and triamcinolone acetonide (TA), examined the expression of known
      GRalpha and GRbeta isoforms, and used gene expression microarrays to compare the
      effects of DEX, FA, and TA on the complete transcriptome in two primary human TM
      cell lines. METHODS: GR binding affinity for DEX, FA, and TA was measured by a
      cell-free competitive radio-labeled GR binding assay. GR-mediated transcriptional
      activity was assessed using the GeneBLAzer beta-lactamase reporter gene assay.
      Levels of GRalpha and GRbeta isoforms were assessed by Western blot. Total RNA
      was extracted from TM 86 and TM 93 cells treated with 1 muM DEX, FA, or TA for 24
      hr and used for microarray gene expression analysis. The microarray experiments
      were repeated three times. Differentially expressed genes were identified by
      Rosetta Resolver Gene Expression Analysis System. RESULTS: The GR binding
      affinity (IC50) for DEX, FA, and TA was 5.4, 2.0, and 1.5 nM, respectively. These
      values are similar to the GR transactivation EC50 of 3.0, 0.7, and 1.5 nM for
      DEX, FA, and TA, respectively. All four GRalpha translational isoforms (A-D) were
      expressed in TM 86 and TM 93 total cell lysates, however, the C and D isoforms
      were more highly expressed relative to A and B. All four GRbeta isoforms (A-D)
      were also detected in TM cells, although GRbeta-D isoform expression was lower
      compared to that of the A, B, or C isoforms. Microarray analysis revealed 1,968
      and 1,150 genes commonly regulated by DEX, FA, and TA in TM 86 and TM 93,
      respectively. These genes included RGC32, OCA2, ANGPTL7, MYOC, FKBP5, SAA1 and
      ZBTB16. In addition, each GC specifically regulated a unique set of genes in both
      TM cell lines. Using Ingenuity Pathway Analysis (IPA) software, analysis of the
      data from TM 86 cells showed that DEX significantly regulated transcripts
      associated with RNA post-transcriptional modifications, whereas FA and TA
      modulated genes involved in lipid metabolism and cell morphology, respectively.
      In TM 93 cells, DEX significantly regulated genes implicated in histone
      methylation, whereas FA and TA altered genes associated with cell cycle and cell
      adhesion, respectively. CONCLUSION: Human trabecular meshwork cells in culture
      express all known GRalpha and GRbeta translational isoforms, and GCs with similar
      potency but subtly different chemical structure are capable of regulating common
      and unique gene subsets and presumably biologic responses in these cells. These
      GC structure-dependent effects appear to be TM cell-lineage dependent.

PMID- 19744341
TI  - Glucosamine suppresses proliferation of human prostate carcinoma DU145 cells
      through inhibition of STAT3 signaling.
AB  - BACKGROUND: Glucosamine is known as a toxic agent for several malignant cell
      lines and transplanted tumors with little toxicity to normal host tissues.
      However, the mechanisms underlying anticancer activity of glucosamine are poorly
      understood. To study the mechanisms, the human prostate cancer DU145 cells were
      used for the model. RESULTS: Glucosamine at concentration 2 mM suppressed
      proliferation and induced death of DU145 cells. Detailed analysis showed that
      glucosamine decreased DNA synthesis, arrested cell cycle at G1 phase and induced
      apoptosis. The effects of glucosamine were associated with up-regulation of
      p21waf1/cip, a CDK inhibitor. Our further studies identified glucosamine as an
      inhibitor of signal transducer and activator of transcription (STAT) 3 which is
      constitutively activated in many cancer cells including DU145 cells. Glucosamine
      inhibited phosphorylation of STAT3 at the Tyr705 residue and as a result, reduced
      STAT3 DNA binding and transcriptional activities. Indeed, the expression of
      apoptosis inhibitor survivin, which is well known target of STAT3, was
      suppressed. Contrary to DU145 cells, glucosamine did not affect proliferation of
      other human prostate cancer PC-3 and C4-2B cells, in which STAT 3 signal pathway
      is not constitutively active. CONCLUSION: Our data identifies glucosamine as a
      suppressor of STAT3 signaling and suggests that anticancer activity of
      glucosamine may be attributed to the suppression of STAT3 activity. Potential
      application of glucosamine for the treatment of tumors with constitutively active
      STAT3 is proposed.

PMID- 19744342
TI  - Erythropoietic protoporphyria.
AB  - Erythropoietic protoporphyria (EPP) is an inherited disorder of the haem
      metabolic pathway characterised by accumulation of protoporphyrin in blood,
      erythrocytes and tissues, and cutaneous manifestations of photosensitivity. EPP
      has been reported worldwide, with prevalence between 1:75,000 and 1:200,000. It
      usually manifests in early infancy upon the first sun exposures. EPP is
      characterised by cutaneous manifestations of acute painful photosensitivity with
      erythema and oedema, sometimes with petechiae, together with stinging and burning
      sensations upon exposure to sunlight, without blisters. These episodes have a
      variable severity depending on the exposure duration and may result in chronic
      permanent lesions on exposed skin. As protoporphyrin is a lipophilic molecule
      that is excreted by the liver, EPP patients are at risk of cholelithiasis with
      obstructive episodes, and chronic liver disease that might evolve to rapid acute
      liver failure. In most patients, EPP results from a partial deficiency of the
      last enzyme of the haem biosynthetic pathway, ferrochelatase, EC 4.99.1.1/FECH
      (encoded by the FECH gene). EPP appears to be inherited as an autosomal dominant
      disease, the clinical expression of which is modulated by the presence of the
      hypomorphic FECH IVS3-48C allele trans, but recessive inheritance with two
      mutated FECH alleles has also been described. In about 2% of patients, overt
      disease was recently shown to be caused by gain-of-function mutations in the
      erythroid-specific aminolevulinic acid synthase 2 (ALAS2/ALAS, EC 2.3.1.27) gene
      and named X-linked dominant protoporphyria. Diagnosis is established by finding
      increased levels of protoporphyrin in plasma and red blood cells, and detection
      of a plasma fluorescence peak at 634 nm. Investigations for hepatic involvement,
      ferrochelatase activity level, genetic analysis (FECH mutations, presence of the
      hypomorphic FECH IVS3-48C allele trans and ALAS2 mutations) and family studies
      are advisable. Differential diagnosis includes phototoxic drug reactions, hydroa
      vacciniforme, solar urticaria, contact dermatitis, angio-oedema and, in some
      cases, other types of porphyria. Management includes avoidance of exposure to
      light, reduction of protoporphyrin levels and prevention of progression of
      possible liver disease to liver failure. As the major risk in EPP patients is
      liver disease, a regular follow-up of hepatic involvement is essential.
      Sequential hepatic and bone marrow transplantation should be considered as a
      suitable treatment for most severe cases of EPP with hepatic involvement. EPP is
      a lifelong disorder whose prognosis depends on the evolution of the hepatic
      disease. However, photosensitivity may have a significant impact on quality of
      life of EPP patients.

PMID- 19744343
TI  - Genome-wide analysis of signal peptide functionality in Lactobacillus plantarum
      WCFS1.
AB  - BACKGROUND: Lactobacillus plantarum is a normal, potentially probiotic,
      inhabitant of the human gastrointestinal (GI) tract. The bacterium has great
      potential as food-grade cell factory and for in situ delivery of biomolecules.
      Since protein secretion is important both for probiotic activity and in
      biotechnological applications, we have carried out a genome-wide experimental
      study of signal peptide (SP) functionality. RESULTS: We have constructed a
      library of 76 Sec-type signal peptides from L. plantarum WCFS1 that were
      predicted to be cleaved by signal peptidase I. SP functionality was studied using
      staphylococcal nuclease (NucA) as a reporter protein. 82% of the SPs gave
      significant extracellular NucA activity. Levels of secreted NucA varied by a
      dramatic 1800-fold and this variation was shown not to be the result of different
      mRNA levels. For the best-performing SPs all produced NucA was detected in the
      culture supernatant, but the secretion efficiency decreased for the less well
      performing SPs. Sequence analyses of the SPs and their cognate proteins revealed
      four properties that correlated positively with SP performance for NucA: high
      hydrophobicity, the presence of a transmembrane helix predicted by TMHMM, the
      absence of an anchoring motif in the cognate protein, and the length of the H+C
      domain. Analysis of a subset of SPs with a lactobacillal amylase (AmyA) showed
      large variation in production levels and secretion efficiencies. Importantly,
      there was no correlation between SP performance with NucA and the performance
      with AmyA. CONCLUSION: This is the first comprehensive experimental study showing
      that predicted SPs in the L. plantarum genome actually are capable of driving
      protein secretion. The results reveal considerable variation between the SPs that
      is at least in part dependent on the protein that is secreted. Several SPs stand
      out as promising candidates for efficient secretion of heterologous proteins in
      L. plantarum. The results for NucA provide some hints as to the sequence-based
      prediction of SP functionality, but the general conclusion is that such
      prediction is difficult. The vector library generated in this study is based on
      exchangeable cassettes and provides a powerful tool for rapid experimental
      screening of SPs.

PMID- 19744344
TI  - Comparative modeling of DNA and RNA polymerases from Moniliophthora perniciosa
      mitochondrial plasmid.
AB  - BACKGROUND: The filamentous fungus Moniliophthora perniciosa (Stahel) Aime &
      Phillips-Mora is a hemibiotrophic Basidiomycota that causes witches' broom
      disease of cocoa (Theobroma cacao L.). This disease has resulted in a severe
      decrease in Brazilian cocoa production, which changed the position of Brazil in
      the market from the second largest cocoa exporter to a cocoa importer. Fungal
      mitochondrial plasmids are usually invertrons encoding DNA and RNA polymerases.
      Plasmid insertions into host mitochondrial genomes are probably associated with
      modifications in host generation time, which can be involved in fungal aging.
      This association suggests activity of polymerases, and these can be used as new
      targets for drugs against mitochondrial activity of fungi, more specifically
      against witches' broom disease. Sequencing and modeling: DNA and RNA polymerases
      of M. perniciosa mitochondrial plasmid were completely sequenced and their models
      were carried out by Comparative Homology approach. The sequences of DNA and RNA
      polymerase showed 25% of identity to 1XHX and 1ARO (pdb code) using BLASTp, which
      were used as templates. The models were constructed using Swiss PDB-Viewer and
      refined with a set of Molecular Mechanics (MM) and Molecular Dynamics (MD) in
      water carried out with AMBER 8.0, both working under the ff99 force fields,
      respectively. Ramachandran plots were generated by Procheck 3.0 and exhibited
      models with 97% and 98% for DNA and RNA polymerases, respectively. MD simulations
      in water showed models with thermodynamic stability after 2000 ps and 300 K of
      simulation. CONCLUSION: This work contributes to the development of new
      alternatives for controlling the fungal agent of witches' broom disease.

PMID- 19744345
TI  - Biomechanical optimization of different fixation modes for a proximal femoral L
      osteotomy.
AB  - BACKGROUND: Numerous proposed surgical techniques have had minimal success in
      managing greater trochanter overgrowth secondary to retarded growth of the
      femoral capital epiphysis. For reconstruction of residual hip deformities, a
      novel type of proximal femur L-osteotomy was performed with satisfactory results.
      Although the clinical outcome was good, the biomechanical characteristics of the
      femur after such an osteotomy have not been clearly elucidated. Therefore, this
      study presents a three dimensional finite element analysis designed to understand
      the mechanical characteristics of the femur after the L-osteotomy. METHODS: A
      patient with left hip dysplasia was recruited as the study model for L-osteotomy.
      The normal right hip was used as a reference for performing the corrective
      surgery. Four FEA models were constructed using different numbers of fixation
      screws but the same osteotomy lengths together with four FEA models with the same
      number of fixation screws but different osteotomy lengths. The von Mises stress
      distributions and femoral head displacements were analyzed and compared. RESULTS:
      The results revealed the following: 1). The fixation devices (plate and screws)
      sustained most of the external loading, and the peak value of von Mises stress on
      the fixation screws decreased with an increasing number of screws. 2). Additional
      screws are more beneficial on the proximal segment than on the distal segment for
      improving the stability of the postoperative femur. 3). The extent of osteotomy
      should be limited because local stress might be concentrated in the femoral neck
      region with increasing length of the L-osteotomy. CONCLUSION: Additional screw
      placement on the proximal segment improves stability in the postoperative femur.
      The cobra-type plate with additional screw holes in the proximal area might
      improve the effectiveness of L-osteotomies.

PMID- 19744347
TI  - Overexpression of human sperm protein 17 increases migration and decreases the
      chemosensitivity of human epithelial ovarian cancer cells.
AB  - BACKGROUND: Most deaths from ovarian cancer are due to metastases that are
      resistant to conventional therapies. But the factors that regulate the metastatic
      process and chemoresistance of ovarian cancer are poorly understood. In the
      current study, we investigated the aberrant expression of human sperm protein 17
      (HSp17) in human epithelial ovarian cancer cells and tried to analyze its
      influences on the cell behaviors like migration and chemoresistance. METHODS:
      Immunohistochemistry and immunocytochemistry were used to identify HSp17 in
      paraffin embedded ovarian malignant tumor specimens and peritoneal metastatic
      malignant cells. Then we examined the effect of HSp17 overexpression on the
      proliferation, migration, and chemoresistance of ovarian cancer cells to
      carboplatin and cisplatin in a human ovarian carcinoma cell line, HO8910.
      RESULTS: We found that HSp17 was aberrantly expressed in 43% (30/70) of the
      patients with primary epithelial ovarian carcinomas, and in all of the metastatic
      cancer cells of ascites from 8 patients. The Sp17 expression was also detected in
      the metastatic lesions the same as in ovarian lesions. None of the 7 non
      epithelial tumors primarily developed in the ovaries was immunopositive for
      HSp17. Overexpression of HSp17 increased the migration but decreased the
      chemosensitivity of ovarian carcinoma cells to carboplatin and cisplatin.
      CONCLUSION: HSp17 is aberrantly expressed in a significant proportion of
      epithelial ovarian carcinomas. Our results strongly suggest that HSp17 plays a
      role in metastatic disease and resistance of epithelial ovarian carcinoma to
      chemotherapy.

PMID- 19744348
TI  - CD133-positive hepatocellular carcinoma in an area endemic for hepatitis B virus
      infection.
AB  - BACKGROUND: CD133 was detected in several types of cancers including
      hepatocellular carcinoma (HCC), which raised the possibility of stem cell origin
      in a subset of cancers. However, reappearance of embryonic markers in de
      differentiated malignant cells was commonly observed. It remained to be
      elucidated whether CD133-positive HCCs were indeed of stem cell origin or they
      were just a group of poorly differentiated cells acquiring an embryonic marker.
      The aim of this study was to investigate the significance of CD133 expression in
      HCC in an area endemic for hepatitis B virus (HBV) infection to gain insights on
      this issue. METHODS: 154 HCC patients receiving total removal of HCCs were
      included. 104 of them (67.5%) were positive for HBV infection. The cancerous and
      adjacent non-cancerous liver tissues were subjected for Western blot and
      immunohistochemistry analysis for CD133 expression. The data were correlated with
      clinical parameters, patient survivals, and p53 expression. RESULTS: Of 154
      patients, 24 (15.6%) had CD133 expression in HCC. Univariate and multivariate
      logistic regression analysis revealed that CD133 expression was negatively
      correlated with the presence of hepatitis B surface antigen (HBsAg). The
      unadjusted and adjusted odds ratios were 0.337 (95%CI 0.126 - 0.890) and 0.084
      (95%CI 0.010 - 0.707), respectively. On the other hand, p53 expression was
      positively associated with the presence of HBsAg in univariate analysis. The
      unadjusted odds ratio was 4.203 (95%CI 1.110 - 18.673). Survival analysis
      indicated that both CD133 and p53 expression in HCC predicted poor disease-free
      survival (P = 0.009 and 0.001, respectively), whereas only CD133 expression
      predicted poor overall survival (P = 0.001). Cox proportional hazard model showed
      that p53 and CD133 expression were two independent predictors for disease-free
      survival. The hazard ratios were 1.697 (95% CI 1.318 - 2.185) and 2.559 (95% CI
      1.519 - 4.313), respectively (P < 0.001 for both). CONCLUSION: In area where HBV
      infection accounts for the major attributive risk of HCC, CD133 expression in HCC
      was negatively associated with the presence of HBsAg, implicating a non-viral
      origin of CD133-positive HCC. Additionally, CD133 expression predicted poor
      disease-free survival independently of p53 expression, arguing for two
      distinguishable hepatocarcinogenesis pathways.

PMID- 19744349
TI  - Reproducibility and comparative validity of a food frequency questionnaire for
      Australian children and adolescents.
AB  - BACKGROUND: Dietary intake during childhood and adolescence is of increasing
      interest due to its influence on adult health, particularly obesity,
      cardiovascular disease and diabetes. There is a need to develop and validate
      dietary assessment methods suitable for large epidemiologic studies of children
      and adolescents. Limited large scale dietary studies of youth have been
      undertaken in Australia, due partly to the lack of a suitable dietary intake
      tool. A self-administered, semi-quantitative food-frequency questionnaire (FFQ),
      the 'Australian Child and Adolescent Eating Survey' (ACAES), was developed for
      youth aged 9-16 years. This study evaluated reproducibility and comparative
      validity of the ACAES FFQ using assisted food records (FRs) as the reference
      method. METHODS: The ACAES FFQ was completed twice (FFQ1 and FFQ2) at an interval
      of 5 months, along with four one-day assisted FRs. Validity was evaluated by
      comparing the average of the FRs with FFQ2 (n = 113) as well as with the average
      of FFQ1 and FFQ2 (n = 101). Reproducibility was evaluated by comparing FFQ1 and
      FFQ2 (n = 101). The two methods were compared using correlations, Kappa
      statistics and Bland-Altman plots. RESULTS: Correlation coefficients for
      comparative validity ranged from 0.03 for retinol to 0.56 for magnesium for
      transformed, energy-adjusted, deattenuated nutrient data, with correlation
      coefficients greater than 0.40 for total fat, saturated fat, monounsaturated fat,
      carbohydrate, sugars, riboflavin, vitamin C, folate, beta-carotene, magnesium,
      calcium and iron. Correlation coefficients for reproducibility ranged from 0.18
      for vitamin A to 0.50 for calcium for transformed, energy-adjusted, deattenuated
      nutrient data. The ACAES FFQ ranked individuals reasonably accurately, with the
      comparative validity analysis showing that over 50% of participants were
      classified within one quintile for all nutrients, with only a small percentage
      grossly misclassified (0-7%). CONCLUSION: The ACAES FFQ is the first child and
      adolescent specific FFQ available for ranking the dietary intakes of Australian
      children and adolescents for a range of nutrients in epidemiologic research and
      public health interventions.

PMID- 19744350
TI  - What evidence is there to support skill mix changes between GPs, pharmacists and
      practice nurses in the care of elderly people living in the community?
AB  - BACKGROUND: Workforce shortages in Australia are occurring across a range of
      health disciplines but are most acute in general practice. Skill mix change such
      as task substitution is one solution to workforce shortages. The aim of this
      systematic review was to explore the evidence for the effectiveness of task
      substitution between GPs and pharmacists and GPs and nurses for the care of older
      people with chronic disease. Published, peer reviewed (black) and non-peer
      reviewed (grey) literature were included in the review if they met the inclusion
      criteria. RESULTS: Forty-six articles were included in the review. Task
      substitution between pharmacists and GPs and nurses and GPs resulted in an
      improved process of care and patient outcomes, such as improved disease control.
      The interventions were either health promotion or disease management according to
      guidelines or use of protocols, or a mixture of both. The results of this review
      indicate that pharmacists and nurses can effectively provide disease management
      and/or health promotion for older people with chronic disease in primary care.
      While there were improvements in patient outcomes no reduction in health service
      use was evident. CONCLUSION: When implementing skill mix changes such as task
      substitution it is important that the health professionals' roles are
      complementary otherwise they may simply duplicate the task performed by other
      health professionals. This has implications for the way in which
      multidisciplinary teams are organised in initiatives such as the GP Super
      Clinics.

PMID- 19744351
TI  - Clinical and neuropathological study about the neurotization of the suprascapular
      nerve in obstetric brachial plexus lesions.
AB  - BACKGROUND: The lack of recovery of active external rotation of the shoulder is
      an important problem in children suffering from brachial plexus lesions involving
      the suprascapular nerve. The accessory nerve neurotization to the suprascapular
      nerve is a standard procedure, performed to improve shoulder motion in patients
      with brachial plexus palsy. METHODS: We operated on 65 patients with obstetric
      brachial plexus palsy (OBPP), aged 5-35 months (average: 19 months). We assessed
      the recovery of passive and active external rotation with the arm in abduction
      and in adduction. We also looked at the influence of the restoration of the
      muscular balance between the internal and the external rotators on the
      development of a gleno-humeral joint dysplasia. Intraoperatively, suprascapular
      nerve samples were taken from 13 patients and were analyzed histologically.
      RESULTS: Most patients (71.5%) showed good recovery of the active external
      rotation in abduction (60 degrees -90 degrees). Better results were obtained for
      the external rotation with the arm in abduction compared to adduction, and for
      patients having only undergone the neurotization procedure compared to patients
      having had complete plexus reconstruction. The neurotization operation has a
      positive influence on the glenohumeral joint: 7 patients with clinical signs of
      dysplasia before the reconstructive operation did not show any sign of dysplasia
      in the postoperative follow-up. CONCLUSION: The neurotization procedure helps to
      recover the active external rotation in the shoulder joint and has a good
      prevention influence on the dysplasia in our sample. The nerve quality measured
      using histopathology also seems to have a positive impact on the clinical
      results.

PMID- 19744352
TI  - A flexible whole-genome microarray for transcriptomics in three-spine stickleback
      (Gasterosteus aculeatus).
AB  - BACKGROUND: The use of microarray technology for describing changes in mRNA
      expression to address ecological and evolutionary questions is becoming
      increasingly popular. Since three-spine stickleback are an important ecological
      and evolutionary model-species as well as an emerging model for eco-toxicology,
      the ability to have a functional and flexible microarray platform for
      transcriptome studies will greatly enhance the research potential in these areas.
      RESULTS: We designed 43,392 unique oligonucleotide probes representing 19,274
      genes (93% of the estimated total gene number), and tested the hybridization
      performance of both DNA and RNA from different populations to determine the
      efficacy of probe design for transcriptome analysis using the Agilent array
      platform. The majority of probes were functional as evidenced by the DNA
      hybridization success, and 30,946 probes (14,615 genes) had a signal that was
      significantly above background for RNA isolated from liver tissue. Genes
      identified as being expressed in liver tissue were grouped into functional
      categories for each of the three Gene Ontology groups: biological process,
      molecular function, and cellular component. As expected, the highest proportions
      of functional categories belonged to those associated with metabolic functions:
      metabolic process, binding, catabolism, and organelles. CONCLUSION: The probe and
      microarray design presented here provides an important step facilitating
      transcriptomics research for this important research organism by providing a set
      of over 43,000 probes whose hybridization success and specificity to liver
      expression has been demonstrated. Probes can easily be added or removed from the
      current design to tailor the array to specific experiments and additional
      flexibility lies in the ability to perform either one-color or two-color
      hybridizations.

PMID- 19744353
TI  - Exon deletions and intragenic insertions are not rare in ataxia with oculomotor
      apraxia 2.
AB  - BACKGROUND: The autosomal recessively inherited ataxia with oculomotor apraxia 2
      (AOA2) is a neurodegenerative disorder characterized by juvenile or adolescent
      age of onset, gait ataxia, cerebellar atrophy, axonal sensorimotor neuropathy,
      oculomotor apraxia, and elevated serum AFP levels. AOA2 is caused by mutations
      within the senataxin gene (SETX). The majority of known mutations are nonsense,
      missense, and splice site mutations, as well as small deletions and insertions.
      METHODS: To detect mutations in patients showing a clinical phenotype consistent
      with AOA2, the coding region including splice sites of the SETX gene was
      sequenced and dosage analyses for all exons were performed on genomic DNA. The
      sequence of cDNA fragments of alternative transcripts isolated after RT-PCR was
      determined. RESULTS: Sequence analyses of the SETX gene in four patients revealed
      a heterozygous nonsense mutation or a 4 bp deletion in three cases. In another
      patient, PCR amplification of exon 11 to 15 dropped out. Dosage analyses and
      breakpoint localisation yielded a 1.3 kb LINE1 insertion in exon 12 (patient P1)
      and a 6.1 kb deletion between intron 11 and intron 14 (patient P2) in addition to
      the heterozygous nonsense mutation R1606X. Patient P3 was compound heterozygous
      for a 4 bp deletion in exon 10 and a 20.7 kb deletion between intron 10 and 15.
      This deletion was present in a homozygous state in patient P4. CONCLUSION: Our
      findings indicate that gross mutations seem to be a frequent cause of AOA2 and
      reveal the importance of additional copy number analysis for routine diagnostics.

PMID- 19744355
TI  - A test of engagement versus disengagement in catastrophe models.
AB  - The present study explored the interactive effects of self-efficacy and
      increasing/decreasing task difficulty upon engagement and disengagement within a
      cusp-catastrophe model framework. Using a closed motor skill aiming task
      participants (N=60) were required to compete in conditions where task difficulty
      increased and then decreased (or vice versa) where they were rewarded for good
      performance but penalized for bad. Participants who reported low levels of self
      efficacy disengage at an earlier level of task difficulty than their high self
      efficacy counterparts. Furthermore, this group did not re-engage with the task
      until task difficulty had significantly decreased. Although task disengagement
      occurred with high difficulty in the high self-efficacy group, this group re
      engaged in a similar manner in which they disengaged. Findings support and extend
      those of previous tests of catastrophe models by directly allowing for task
      disengagement.

PMID- 19744354
TI  - Dietary patterns associated with metabolic syndrome, sociodemographic and
      lifestyle factors in young adults: the Bogalusa Heart Study.
AB  - OBJECTIVE: To examine the association between dietary patterns (DP) and risk for
      metabolic syndrome (MetS); and to identify differences in DP by socio-economic,
      demographic and lifestyle factors. DESIGN: Dietary intake (from an FFQ),
      anthropometric/biochemical parameters and sociodemographic/lifestyle information
      (from a self-reported questionnaire) were evaluated, using a cross-sectional
      design. Statistical methods included principal component factor analysis,
      analysis of covariance and linear regression. All analyses were covariate
      adjusted. SETTING: The Bogalusa Heart Study (1995-1996), USA. SUBJECTS: Young
      adults (19-39 years; n 995; 61 % females/39 % males; 80 % whites/20 % blacks)
      from a semi-rural southern US community were examined. RESULTS: The 'Western
      Dietary Pattern' (WDP) consisted of refined grains, French fries, high-fat dairy
      foods, cheese dishes, red meats, processed meats, eggs, snacks, sweets/desserts,
      sweetened beverages and condiments. The 'Prudent Dietary Pattern' (PDP) consisted
      of whole grains, legumes, vegetables, fruits, 100 % fruit juices, low-fat dairy
      products, poultry, clear soups and low-fat salad dressings. The DP explained 31 %
      of the dietary intake variance. Waist circumference (P = 0.02), triceps skinfold
      (P = 0.01), plasma insulin (P = 0.03), serum TAG (P = 0.05), and the occurrence
      of MetS (P = 0.03) were all inversely associated with PDP. Insulin sensitivity (P
      < 0.0005) was positively associated with PDP. Serum HDL cholesterol (P = 0.05)
      was inversely associated with WDP. Blacks consumed more servings from WDP than
      whites (P = 0.02). Females consumed more servings from PDP than males (P =
      0.002). Those with >12 years of education consumed more servings from PDP than
      their counterparts (P < 0.0001). Current smokers consumed more servings from WDP
      than current non-smokers (P < 0.0001). Physically very active young adults
      consumed fewer servings from WDP than their sedentary counterparts (P = 0.02).
      CONCLUSIONS: More studies are warranted to confirm these findings in other
      populations.

PMID- 19744356
TI  - Monitoring of self-generated speech in adolescents with 22q11.2 deletion
      syndrome.
AB  - OBJECTIVES: The present report examines the monitoring of self-generated speech
      in adolescents with 22q11.2 deletion syndrome (22q11DS), a neurogenetic disorder
      associated with very high risk for psychosis. DESIGN: Between-participant group
      design. METHODS: In this study, 20 adolescents with 22q11DS, 19 age- and IQ
      matched controls, and 19 typically developing adolescents were enrolled.
      Participants completed a speech-monitoring task, in which they were asked to
      silently or overtly read a series of word and non-word items. Subjects then
      filled out a recognition sheet containing studied and novel items. They were
      asked to identify the previously studied item, and to attribute the reading
      condition (silent vs. overt) under which each recognized item was encoded.
      RESULTS: Adolescents with 22q11DS commit more external attribution errors
      compared to both control groups, by exhibiting an increased tendency to report
      silently read items as though they had been read overtly. Further, results
      suggest that increased cognitive effort exacerbates the external attribution
      tendency in adolescents with 22q11DS. Increased internal attributions were also
      observed in the IQcontrol and 22q11DS groups in comparison to typically
      developing adolescents. CONCLUSIONS: Similarly to adult individuals exhibiting
      positive symptoms of psychosis, adolescents with 22q11DS exhibit an external
      attribution bias for inner speech. This bias seems to be exacerbated by increased
      cognitive effort, suggesting a failure to recollect information pertaining to
      cognitive operations during self-monitoring. Cognitive biases associated to
      schizophrenia may be detected in adolescents at very high risk for psychosis.
      These observations provide further evidence for the presence of an external
      attribution bias along the clinical continuum of psychosis vulnerability.

PMID- 19744357
TI  - Appalling and appealing: a qualitative study of the character of men's self-harm.
AB  - OBJECTIVES: To engage with the experiential phenomena of men's self-harm, to get
      a sense of its 'feel', its character, and to relate these things in a useful and
      authentic way. DESIGN: Qualitative in-depth interview study with design input
      from service users' groups. METHOD: Hermeneutic phenomenology. Two interviews
      with each of four participants in their homes, with the intention of developing
      understanding through dialogic interview and reflection. RESULTS: Some of the
      character of men's self-harm was recognizable from the psychodynamic and
      functional literature: soothing practices, dissociation, and an ambivalent
      stuckness around separation versus incorporation. There were other, unexpected
      structures present: existential vulnerability and openness, sacrifice, lack of
      boundary, and insatiability. CONCLUSIONS: Professionals who work with men who
      self-harm may like to be aware of these relational dynamics.

PMID- 19744358
TI  - Non-clinical obsessions in a young adolescent population: frequency and
      association with metacognitive variables.
AB  - OBJECTIVES: Little is known about normal obsessions in adolescence. This study
      examined the frequency and content of intrusions in adolescence, and a number of
      process variables that have been associated with obsessions in adults. DESIGN AND
      METHODS: Sixty-two adolescents (aged 12-14 years) participated. They completed
      measures of obsessions and metacognitive beliefs. They were interviewed about
      recent episodes of obsessional thought, including content, frequency,
      acceptability, distress, dismissibilty, interference, and avoidance. RESULTS:
      Seventy-seven per cent of participants reported obsessions. Frequency, distress,
      dismissibility, acceptability, interference, and avoidance, were associated with
      metacognitive appraisals. CONCLUSIONS: Obsessions are a normal experience in
      adolescence and are associated with metacognitive appraisals in the same way as
      for adults, indicating that adult models may be relevant for this younger
      population.

PMID- 19744359
TI  - Clinical showcase. Replacement of congenitally missing lateral incisor using a
      metal-free, resin-bonded fixed partial denture: case report.

PMID- 19744360
TI  - Recommendations for antibiotics in patients with joint prosthesis are
      irresponsible and indefensible.

PMID- 19744361
TI  - Time to improve access to oral health care for persons with special needs.

PMID- 19744362
TI  - Functional and psychosocial impacts of oral disorders in Canadian adults: a
      national population survey.
AB  - BACKGROUND: In Canada, national health surveys do not usually include questions
      pertaining to self-perceived oral health. Those that do use ad hoc sets of
      questions rather than standardized and validated measures of the functional and
      psychosocial impacts of oral disorders. AIMS: To collect national data on the
      impacts of oral disorders from a representative sample of Canadian adults and to
      compare the results with similar national surveys conducted in the United Kingdom
      and Australia. METHODS: Data were collected from adults by means of a telephone
      interview survey based on random-digit dialing. Oral health was measured with the
      short-form Oral Health Impact Profile (also known as the OHIP-14 questionnaire),
      which asks about the frequency of 14 functional and psychosocial impacts that
      people have experienced in the previous year as a result of problems with their
      teeth, mouth or dentures. RESULTS: Of 3,033 interviews conducted, data were
      sufficient for analysis for 3,019 respondents. Just under one-fifth of the 3,019
      respondents (19.5%) reported 1 or more of the 14 impacts "fairly often" or "very
      often" in the previous year. The prevalence was higher among edentulous
      respondents (30.7%) than among dentate respondents(18.6%), as were the extent and
      severity scores. The prevalence of impacts was lowest in Atlantic Canada (16.1%)
      and highest in the Prairies (23.3%), although the difference was not
      statistically significant. Prevalence rates and extent and severity scores were
      highest among those who wore dentures, recipients of public dental care and
      irregular dental visitors. Considerable income disparities were also observed,
      with 34.9% of those from the lowest-income households reporting impacts. The
      prevalence of effects and the extent and severity scores in Canada were similar
      to those reported from the United Kingdom and Australia. CONCLUSIONS: One in 5
      Canadian adults experienced adverse impacts from oral disorders. Further work is
      needed to identify the material and psychological determinants of these impacts.

PMID- 19744363
TI  - Oral herpes simplex virus infection in pregnancy: what are the concerns?
AB  - Although epidemiologic data and the potentially serious effects of transmission
      of genital herpes from mother to infant during birth have been widely reported,
      published reports on oral herpes disease in pregnancy remain scarce and no clear
      management guidelines exist. Thus, questions remain about acquisition,
      transmission and outcome of infection, especially with respect to acute
      gingivostomatitis in pregnancy. In response to these questions, we summarize
      previous reports on herpes simplex virus 1 (HSV-1) oral disease in pregnancy and,
      briefly, present 2 cases of primary gingivostomatitis in the first trimester of
      pregnancy, resulting in a favourable outcome for both mother and infant. We also
      point out the most recent data on rare, potentially severe in outcome, but
      treatable, primary central nervous system HSV-1 infection in later stages of
      pregnancy. Finally, we emphasize a multidisciplinary approach to oral HSV disease
      in pregnancy, with dentist participation in the diagnosis and treatment.

PMID- 19744364
TI  - Osler-Weber-Rendu syndrome--dental implications.
AB  - Osler-Weber-Rendu syndrome (OWRS) is a rare hereditary, autosomal dominant
      disease characterized by a local angiodysplasia. Its clinical characteristics are
      vascular hamartomas of the skin and oral mucosa, arteriovenous malformations in
      the lungs, liver, kidney and brain, and episodes of epistaxis. The oral lesions,
      which become apparent through hemorrhagic telangiectasia, may be the first sign
      of the disease. This is a case report of a 74-year-old woman whose diagnosis of
      OWRS was established by her dentist based on the presence of telangiectasia in
      the skin and oral mucosa, reports of frequent nosebleeds of unknown etiology and
      a family history of telangiectasia. Amputation of a lower limb and comorbidities,
      such as cardiopathy, nephropathy and rheumatic disorders, completed the profile.
      OWRS causes major vascular changes that can be diagnosed initially by a dentist.
      In this article, we describe the skills and knowledge that dentists need to
      monitor patients with OWRS properly.

PMID- 19744365
TI  - Oral manifestations of vitamin B12 deficiency: a case report.
AB  - Megaloblastic anemias are a subgroup of macrocytic anemias, in which distinctive
      morphologic abnormalities occur in red cell precursors in bone marrow, namely
      megaloblastic erythropoiesis. Of the many causes of megaloblastic anemia, the
      most common are disorders resulting from cobalamin or folate deficiency. The
      clinical symptoms are weakness, fatigue, shortness of breath and neurologic
      abnormalities. The presence of oral signs and symptoms, including glossitis,
      angular cheilitis, recurrent oral ulcer, oral candidiasis, diffuse erythematous
      mucositis and pale oral mucosa offer the dentist an opportunity to participate in
      the diagnosis of this condition. Early diagnosis is important to prevent
      neurologic signs, which could be irreversible. The aim of this paper is to
      describe the oral changes in a patient with megaloblastic anemia caused by a
      dietary deficiency of cobalamin.

PMID- 19744366
TI  - Application of a photochromic dye in an automatic welding filter.
AB  - The main purposes of this study were to select a photochromic dye and to develop
      an active welding filter with a photochromic layer. A series of functionalized
      spirobenzopyranoindolins were synthesized and their photophysical and
      photochemical properties were investigated in a solution using absorption and
      emission spectroscopy. Time-resolved fluorescence spectroscopy measurements were
      used to characterize the decays and rate constants of fluorescence emission. One
      dye was selected as a suitable photoactive compound in automatic welding filters.
      A model of an active welding filter with a photochromic layer based on 1',3',3'
      trimethyl-6-nitrospiro[2H-1-benzopyran-2,2'-indole] (6-nitroBIPS) was developed.
      The paper presents the results of tests of the filter conducted according to EN
      standards.

PMID- 19744367
TI  - Understanding the effect of speed of exertion on isokinetic strength using a
      multiaxial dynamometer.
AB  - In this study a multiaxial isokinetic dynamometer was used to measure strength
      during various upper-body isokinetic exertions. Ten male participants performed 7
      different upper-body isokinetic exertions. In addition, to evaluate the effect of
      speed on strength, each participant performed sitting pull exertions at the speed
      of 0.026, 0.130, and 0.260 m/s. Average isokinetic strength increased from 236.6
      +/- 39.1 to 291.8 +/- 65.8 N with the initial increase in speed from 0.026 to
      0.130 m/s. The average isokinetic strength decreased to 276.7 +/- 87.2 N with a
      further increase in speed to 0.260 m/s. The curve between isokinetic strength and
      speed followed a bell-shaped curve (fitted with the Gaussian function, R(2) =
      .9). The results of this study could be useful in deciding on the work pace of
      various manual material handling tasks requiring maximal and/or near maximal
      exertions.

PMID- 19744368
TI  - Corrosion of retractable type fall arresters.
AB  - Retractable type fall arresters constitute a most effective group of components
      used in personal protection systems protecting against falls from a height. They
      are designed primarily for outdoor use, which results in exposure to atmospheric
      factors associated with risk of corrosion of metal elements. This paper presents
      the results of a study, in which retractable type fall arresters were exposed to
      a simulated corrosive environment, a neutral salt spray. It discusses the
      development of corrosion processes depending on the duration of exposure to
      corrosive conditions. Tests demonstrated that corrosion of elements decreased
      their strength and impaired the functioning of mobile parts. The article presents
      methods of testing the correct functioning of devices, necessary for assessing
      their resistance to corrosion, which have been developed for this purpose. It
      also analyzes the correlation between corrosion-related damage of retractable
      type fall arresters and potential hazards for their users.

PMID- 19744369
TI  - A study on the combined effect of noise and vibration on the performance of a
      readability task in a mobile driving environment by operators of different ages.
AB  - This study investigated the combined effect of noise and vibration on the
      performance of a readability task in a mobile driving environment by operators of
      different ages. Subjects performed a readability task on a laptop computer in a
      sitting posture without their backs supported under varying levels of noise and
      vibration. Data in terms of a mean number of characters read per minute were
      collected and statistically analyzed. Results showed that the individual effects
      of noise, vibration, and operators' age as well as the interaction between
      operators' age and vibration were statistically significant. However, the
      combined effect of noise and vibration was not found to be statistically
      significant. Results also indicated that the operators' age was statistically
      significant at all levels of vibration and vibration was statistically
      significant at all levels of operators' age.

PMID- 19744370
TI  - Attenuation of noise by motorcycle safety helmets.
AB  - For workers such as police motorcyclists or couriers, traffic and engine noise
      reaching the ears is an important factor contributing to the overall condition of
      their work. This noise can be reduced with motorcycle helmets. In this study,
      insertion loss of motorcycle helmets was measured with the microphone-in-real-ear
      technique and sound attenuation with the real-ear-at-threshold method. Results
      for 3 Nolan helmets show essentially no protection against external noise in the
      frequency range <250 Hz. In the frequency range >500 Hz, attenuation increases
      linearly at a rate of 8-9 dB per octave, to ~30 dB at 8 kHz. Lack of attenuation
      in the low-frequency range may cause annoying effects. In addition, high
      attenuation in the high-frequency range may decrease intelligibility of speech
      signals for a rider in a helmet. Attenuation measured in this study does not take
      into account noise generated by turbulent wind around the helmet. Thus, the
      measured values of attenuation represent a motorcycle rider's best conditions of
      hearing.

PMID- 19744371
TI  - The effect of an active lumbar system on the seating comfort of officers in
      police fleet vehicles.
AB  - The purposes of this study were to determine which seat features/occupational
      demands contributed to police officer discomfort and whether an automobile seat
      fitted with an active lumbar system (ALS) could reduce driving discomfort. Fifty
      eight officers were given questionnaires to assess driving discomfort. High
      discomfort levels were associated with computer use, duty belt, sidearm/radio,
      body armour and lumbar support interface. Discomfort was highest in the lumbar,
      sacrum, upper pelvis and mid-back regions. Twelve officers spent one shift each
      in a police vehicle seat and an ALS seat. Discomfort was assessed every 2 h
      during 8-h shifts. Reduced discomfort was reported with the ALS seat. Three
      lumbar support features, the duty belt, and the lumbar and right upper pelvis
      regions, showed reduced discomfort. Overall seat discomfort decreased by 47%
      after 8 h of exposure to the ALS. Modifying the automobile seat helps to reduce
      officer discomfort during prolonged vehicle usage.

PMID- 19744372
TI  - Ergonomics hazards analysis of linemen's power line fixing work in China.
AB  - This study used qualitative and quantitative methods, such as OWAS (Ovako working
      posture analysis system) and behavior observation, to analyze musculoskeletal
      disorder (MSD) risk factors of power line fixing work in China. Video-based
      sampling was used to record and analyze the frequency and posture of on-pole
      activities. Those key subtasks showed ergonomics characteristics of on-pole
      fixing tasks. Insulator-fixing was the longest subtask (33% of total working
      time). Bar-installing was the second longest (26% of total working time). It was
      evident that bar-installing and insulator-fixing were full of hazardous risks.
      The action categories of the 2 subtasks were higher than of the other ones. The 2
      subtasks were also time-consuming, difficult and induced MSDs. Assistant linemen
      faced more hazardous factors than chief linemen.

PMID- 19744373
TI  - Work ability and musculoskeletal disorders among workers from a public health
      institution.
AB  - OBJECTIVE: The study investigated the associations between diagnosed
      musculoskeletal disorders (MSD), work ability and demographics, work and
      lifestyle characteristics in a public health institution with a variety of
      occupations. METHODS: A cross-sectional study was carried out in a public health
      institution in Brazil. The subjects (n = 168) aged 20-69 answered a questionnaire
      on demographics, work, lifestyle characteristics and the work ability index.
      RESULTS: A univariate regression analysis was carried out with the presence of
      MSD as a dependent variable. Association was found in relation to the age group,
      type of work demand, tenure at the institution, body mass index, work in the
      nutrition and laundry sectors, being a maid in the previous job, auxiliary
      service and auxiliary maintenance occupations, work ability in relation to
      physical and mental demands, estimated work impairment due to diseases, sick
      leave in the past year, own prognosis of work ability in 2 years' time and mental
      resources: enjoying daily activities, being active and alert, being full of hope
      for the future. CONCLUSION: The presence of MSD affected several aspects of work
      ability.

PMID- 19744374
TI  - Using ergonomics checkpoints to support a participatory ergonomics intervention
      in an industrially developing country (IDC)--a case study.
AB  - To achieve ergonomics awareness in 3 subsidiary companies, an intervention team
      was formed. The aims of this study were to implement basic ergonomics through a
      participatory ergonomics intervention process that can support a continuous
      learning process and lead to an improvement in health and safety as well as in
      the work systems in the organization. The findings of this study (i.e., method,
      continuous learning and integration) were key to making the participatory
      ergonomics intervention successful. Furthermore, 4 issues of the ergonomics
      checkpoints (i.e., work schedules, work tasks, healthy work organization and
      learning) for assessing the work system were found suitable for both changing
      work schedules and for improving the work system. This paper describes the result
      of this project and also the experiences gained and the conclusions reached from
      using the International Labour Office's ergonomics checkpoints in the industries
      of industrially developing country.

PMID- 19744375
TI  - Effects of polyphenol on visual fatigue caused by VDT work.
AB  - Visual fatigue of VDT (visual display terminal) operators poses a serious problem
      for corporations where VDT work is a major part of operations. In this study, an
      investigation in a corporation was carried out to examine the effect of
      polyphenol on recovery from visual fatigue of the visual function caused by
      working at a VDT. Three kinds of parameters were used for evaluating the effect
      of polyphenol. As a subjective evaluation, the first was a questionnaire to
      ascertain subjective feelings of fatigue. As aspects of a physiological
      evaluation, the second and third parameters were the accommodative function and
      the flicker value.

PMID- 19744376
TI  - [The serum levels of cholesterol and statins].

PMID- 19744377
TI  - [The searching discover of statins and the Lasker prize].

PMID- 19744378
TI  - [The hyperlipidemia diagnosis based on phenotype].
AB  - OBJECTIVE: to describe the different clinical profiles of patients with
      dyslipidemia based on lipid phenotype, in an urban setting. METHODS: a survey was
      carried out among college students and general population. A structured interview
      was conducted. Blood was drawn for glucose and lipid profile from subjects
      considered to be healthy. RESULTS: we included 1286 subjects. They were grouped
      by socioeconomic status (low income = 437, medium income = 162 and high income =
      133) and 554 college students who had lived in the area for at least one year.
      Women composed 61 % of the cohort; 86 % of the cases were studied after an
      overnight fasting period. The prevalent lipid phenotype was
      hypoalphalipoproteinemia, followed by mixed hyperlipidemia. Among medium income
      group, isolated hypercholesterolemia was a common finding. High fasting glucose
      and low c-HDL were observed among the low income group. Male gender and age are
      predictors for hypercholesterolemia. The BMI is the only identified predictor of
      hypertriglyceridemia (OR = 10.089). We identified that age > 55-year old (OR =
      2.6), male gender (OR = 1.6), and sedentary life (OR = 1.35), were predictors of
      hypoalphalipoproteinemia. CONCLUSION: the most common lipid phenotype was
      hypoalphalipoproteinemia.

PMID- 19744379
TI  - [Periodontal diseases and treatment needs in diabetes type 2].
AB  - OBJECTIVE: to determine the prevalence of periodontal disease and the needs for
      treatment in patients with diabetes mellitus type 2 (DM2) in a rural population.
      METHODS: a transversal descriptive study with bivariate analysis was carried out.
      Gender, age, smoking habit and blood glucose levels were obtained from the
      clinical files in 94 cases. A periodontal examination was carried out by the
      Periodontal Index of Community Treatment Needs. RESULTS: the ratio woman-man was
      3:1. Age rate was from 35 to 75 years, with a mean of 53.4. Fifty two percent of
      the subjects had been diagnosed in the last five years; 78 percent of the
      subjects were moderately and badly controlled on diabetes parameters; 96.8
      percent of the individuals had moderate to severe periodontal disease with the
      need for specialized periodontal treatment. CONCLUSIONS: the chronic mouth
      infections should be seriously considered for an adequate metabolic control of
      diabetic patients.

PMID- 19744380
TI  - [Visceral fat and metabolic manifestations in hypertensive men].
AB  - OBJECTIVE: to determine visceral fat and metabolic profile in hypertensive men
      with and without obesity. METHODS: analytic cross-sectional study was carried
      out. Thirty hypertensive men with obesity and 30 hypertensive men without obesity
      from a primary care clinic. Visceral and subcutaneous fat (by computer axial
      tomography), anthropometry, lipid profile, fibrinogen, and glucose (fasting and 2
      hr after glucose load) were measured. RESULTS: hypertensive obese men were
      younger (48 + or - 7 versus 57 + or - 6 years) who had higher values of blood
      pressure, lipids and lipoproteins, waist and hip circumference and total
      abdominal and subcutaneous fat (420 versus 321 cm(2), p < 0.001; and 257 versus
      162 cm(2), p = 0.03). Visceral fat was similar in both groups (163 versus 162
      cm(2)). The non obese group had higher levels of glucose either fasting and post
      glucose load. Both groups had increased mean values of fibrinogen and
      triglycerides and low concentrations of HDL-c. CONCLUSIONS: hypertension was
      associated with increased visceral fat, regardless the BMI. Although obese
      hypertensive men were younger, they had a metabolic profile more deleterious than
      non obese men.

PMID- 19744381
TI  - [Clinical aptitude to treat late diabetes complications].
AB  - BACKGROUND: the lack of medical education is the main factor that contributes to
      cause late complications in diabetes mellitus (DMC). Our objective was to
      determine the clinical skills of family physicians to prevent, diagnosis and
      treat late DMC. METHODS: a comparative cross-sectional study was made. To know
      the level of the clinical skill in family physicians treating late DMC. The study
      was based on a comparison between years of experience and recognition of
      indicators. An instrument was constructed and validated. It was conformed by
      three clinical cases and 184 items; the study obtained acceptable rates of
      reliability through three statistical tests. It was applied to 189 family
      specialized physicians through a census. RESULTS: most of the physicians (73.5 %)
      were located at primary care level. There were statistically significant
      differences among the four zones of attention (p = 0.0001 Kruskal-Wallis), and
      among their years of experience (p = 0.0001 Kruskal-Wallis) and among who had or
      did not have private medical practice (p = 0.05 of Mann-Whitney). CONCLUSIONS:
      the clinical aptitude of the family physicians studied is low. The results are
      reflecting the model of education that predominates.

PMID- 19744382
TI  - [Periventricular leukomalacia prevalence in premature newborn].
AB  - BACKGROUND: the periventricular leukomalacia (PLM) is considered a lesion of the
      central nervous system secondary to a hypoxic-ischemic insult, and affects more
      to premature than term neonates. However, the reported rates in the literature
      are between 2 % to 25 % in premature neonates. The objective was to determine the
      prevalence of PLM in premature neonates. METHODS: a two year prospective
      screening program with transfontanel ultrasound in premature neonates weighing <
      2000 g was carried out at 4 weeks of age. RESULTS: from 38 355 consecutive
      deliveries 562 were premature neonates weighted = 2000 g who fulfilled inclusion
      criteria and all were studied with transfontanel ultrasonography; we found 36
      (6.34 %) premature neonates with PLM. Of the 346 neonates weighing = 1500 g, 26
      (7.5 %) had a positive examination for PLM. In the 1501 g to 2000 g group, 10 of
      216 (4.6 %) had PLM. The PLM prevalence was higher in male (2:1). Neurological
      exam was normal at the time of study. CONCLUSIONS: the PLM was present in 6.3 %
      of premature neonates weighing < 2000 g with 2 affected males for each female.

PMID- 19744383
TI  - [Clinical and metastatic characteristics in retinoblastoma].
AB  - BACKGROUND: retinoblastoma is an intraocular malignancy of the childhood. Tumor
      invasion and metastases are the cause of mortality. The objective was to
      determine the clinical characteristics, the appearance and site of metastases in
      patients with retinoblastoma. METHODS: descriptive, observational, retrospective
      and cross-sectional study was carried out. We reviewed 86 patients with
      retinoblastoma. RESULTS: the average age was 24.5 months. There were 51.2 %
      women. 75.6 % had unilateral presentation and 24.4 % bilateral; two of these were
      trilateral The clinical manifestation were leukokoria, strabismus and glaucoma.
      We found metastatic disease in 18 patients (20 %), being the central nervous
      system (CNS) and bones frequently affected. The metastases odds ratio was 3.50
      associated to choroidal invasion; 6.25 for patients with invasion to optical
      nerve with edge with tumor; 3.75 for which they had choroidal invasion and optic
      nerve with free edge and 5.62 for patients with choroidal invasion and optic
      nerve with surgical edge with tumor. CONCLUSIONS: choroidal invasion and surgical
      edge with tumor showed a greater relative risk for development of metastatic
      disease. The sites commonly affected were the CNS and bones.

PMID- 19744384
TI  - [Summarized real clinical cases use to learn clinical aptitude].
AB  - OBJECTIVE: to evaluate clinical skills indicators (CSI) with summarized real
      clinical cases (SRCC) by two generations of pregraduates interns. METHODS: with a
      descriptive survey design 430 SRCC were elaborated according to the CSI: risk
      factors, clinical diagnosis, laboratory and x-ray diagnosis, commission and
      omission iatrogenesis procedures, therapeutics, nosology and peer critical
      medical actions. An evaluation scale for the clinical cases included: a
      relationship with the clinical experience, and the CSI selected. The final
      evaluation was considered as adequate or inadequate and was performed
      independently by three medical social service students. RESULTS: except for
      family medicine, the SRCC were related to the clinical experience of the
      students. A 62 % of the total was considered as adequate. The CSI assessed were
      related to risk factors (18 %), clinical diagnosis (32 %), omission and
      commission iatrogenesis (9 %), laboratory and x-ray diagnosis resources (16 %),
      therapeutics (17 %), nosology (9 %) and a critical to peer medical actions (3 %).
      CONCLUSIONS: the SRCC patients studied from different points of view by the
      interns included the CSI. Therefore, this action is advisable for the improvement
      of the patients' clinical approach.

PMID- 19744385
TI  - [Critical reading of theoretical texts in family physicians].
AB  - BACKGROUND: the critical reading is skill which allows to extend the reality that
      surrounds us, and strengthens our own point of view, through the reflection of
      the experience. Our objective was to consider the reach of a participative
      educational strategy (PES) for the development of an skill for critical
      theoretical text reading in family physician residents. METHODS: interventional
      study in a group of family physician junior residents who were measure at the
      beginning and the end, comparing with a single measurement of a group of senior
      residents. The strategy was carried out in two ways: individual and group work.
      In order to determine the advancement of the intervention, an evaluation
      instrument with two indicators was applied: understanding and interpretation.
      RESULTS: a significant advance in the interpretation indicator was observed, the
      global result and the understanding indicator did not show significant changes.
      When comparing the group with senior residents significant differences in the
      global result and the indicator of interpretation were observed. CONCLUSIONS: the
      strategy caused the development of the skills for the critical theoretical text
      reading.

PMID- 19744386
TI  - [A pragmatic vision of medical education].
AB  - Some aspects of the educative system at the Mexican Institute of Social Security
      are described. It is based on the perception of a problematic situation that
      constitutes a challenge. An educational process to enhance the quality of medical
      education is proposed, with the adoption of a participative model of self
      constructive learning. This proposal is based on theoretical references in a both
      philosophical and sociological knowledge perspective of an individual related to
      institutional behavior, to end with a psychological view from which some learning
      theories are explored. An educational model is built with the inclusion of
      institutional elements, like the new evaluation system for residents; centers for
      educational investigation and a teacher training process. Three axes of the
      educational process are proposed: tutorial teaching, development of complex
      abilities of thought and critical reading. The evaluation system includes guides
      for measuring the operational process established and the professional
      responsibilities of the different participants.

PMID- 19744387
TI  - [Risk factors associated with upper gastrointestinal bleeding and with
      mortality].
AB  - OBJECTIVE: to determine the associated risk factors with upper gastrointestinal
      bleeding (UGIB) and mortality in subjects with peptic ulcer. METHODS: a total of
      345 subjects with peptic ulcer, < 60 years of age, were enrolled in a cross
      sectional study. Subjects were allocated into one of two groups in accordance
      with the presence of UGIB. A logistic regression model, adjusted by age and sex,
      was used to compute the relationship between the risk factors and both UGIB and
      mortality. RESULTS: smoking (OR = 2.6, CI 95 % = 1.2-8.7), alcohol consumption
      (OR = 4.8, CI 95 % = 1.4-10.5), and previous history of UGIB (OR = 1.8, CI 95 % =
      1.1-9.7) were strongly and independently associated with UGIB; chronic
      obstructive pulmonary disease (OR = 1.9, CI 95 % = 1.2-11.4), and high blood
      pressure (OR = 1.4, CI 95 % = 1.1- 7.5) were associated with mortality in UGIB.
      CONCLUSIONS: the associated risk factors with UGIB in patients with peptic ulcer
      were: age lower than 60 years; smoking; history of UGIB; and alcohol consumption.
      The chronic obstructive pulmonary disease and high blood pressure were associated
      with mortality in UGIB.

PMID- 19744388
TI  - [The morbidity and mortality in vaginal hysterectomy performed with bipolar
      electrosurgery].
AB  - OBJECTIVE: to know the morbidity and mortality in vaginal hysterectomy (VH)
      carried out with bipolar electrosurgery (BiClamp). METHODS: a multicentric study
      with 380 patients who underwent to VH for benign illness, with and without
      prolapse, with and without abdominal previous surgeries using Biclamp was carried
      out. RESULTS: twenty five patients (6.57 %) presented complications. The most
      frequent were related to the urinal system and infection, when VH was carried
      out. Bladder injury in five cases (1.31 %), vesicular-vagina fistula in two cases
      (0.52 %). Vaginal vault abscesses in seven cases (1.84 %). A second surgery due
      to intra abdominal bleeding in four cases (1.05 %) was carried out. Vaginal vault
      bleeding was present in two cases (0.52 %); other complications were: hematoma in
      vaginal vault, thrombophlebitis, sepsis and death with one case (0.26 %) for each
      one. The injuries were repaired by a gynecologist and the fistulae by an
      urologist. The bleeding was inmediately remedied and the infection was treated
      with cephalosporin. CONCLUSIONS: the morbidity and the operative mortality were
      in the range reported in the literature. This technique is quicker, less
      invasive, with a prompt patient recovery.

PMID- 19744389
TI  - [Dental characteristics of patients with temporomandibular disorders].
AB  - OBJECTIVE: to describe the dental characteristics of patients with
      temporomandibular disorders (TMD). METHODS: a survey in 130 out patients from a
      Clinic of Maxilofacial Surgery Service, who fulfilled the selection criteria. The
      social and demographic data were reported in other paper. It was used a
      questionnaire to identify factors of risk for TMD according to the Research
      Diagnostic Criteries/Temporomandibular Disorders proposed by Dworkin. It was
      registered the Angle to molar bilaterally and canine, the presence of canine
      guides and incisal margin, the dental lost organs and previous surgical removal
      of third molars. Unvaried and bivariate statistical analysis was made. RESULTS:
      the clinical manifestations in patients with TMD which they appear in the
      upheavals temporomandibular were: pain to articulate, muscular pain, noises you
      will articulate with statistically significant differences (p < 0.05) in the
      variables class to molar and canine of Angle, absence of canine guides and
      incisal margin, previous retirement of third molars, parafunctions, mandibulars
      deviations at rest, number of dental absences. CONCLUSIONS: the physiomechanical
      conditions in the oral cavity of the patients of upheavals temporomandibular are
      considered a risk factor condition.

PMID- 19744390
TI  - [A clinical and therapeutic analysis in acute megakaryoblastic leukemia].
AB  - OBJECTIVE: to show clinical and therapeutic findings in patients with diagnosis
      of acute megakaryoblastic leukemia (AML). METHODS: twenty four patients with
      diagnosis AML was carried out. Clinical, laboratory survey results and treatment
      response were studied. Nineteen patients had primary form and five secondary,
      attended during a period of eight years. The diagnosis was established by a
      highly clinical suspicious, with immunophenotype cytometry flow or/and bone
      biopsy with immunohistochemistry study which proves definitely AML. RESULTS:
      Fourteen were women, the median age was 43 years, 18 were treated with
      antineoplasic agents, ten obtained response, six complete and four partial. The
      response may improve with schemes with high dose of cytosine arabinoside.
      CONCLUSIONS: our results with the treatment showed that 27 % patients are alive
      under maintenance treatment long 18 months. The allogeneic bone marrow transplant
      seems to be one more option in long term.

PMID- 19744391
TI  - [A proposal to evaluate the productivity and accuracy in diagnostic studies].
AB  - OBJECTIVE: to assess the productivity in an Oncology Hospital (OH) and to assess
      the diagnostic accuracy. METHODS: an analysis focused on the specimen type
      received in three General Hospitals (GHs) and one OH was carried. Diagnostic
      categories were established according with the complexity of the steps involved
      in the production of a pathology report, the analysis also took in consideration
      costs. Three monthly plans were created for monitoring the accuracy diagnosis.
      RESULTS: four categories of specimen type and diagnostic complexity were found.
      At the OH, 13,381 cases were studied, of which 7745 (56 %) belong to the number 4
      difficult cases category. About 2500 specimens came from each of the three GHs
      involved, of which 1825 cases (73 %) belong to the routine cases category. The
      income rate for the OH was that of 52,714,940 pesos as compared with $4,413,800
      for the GHs. Routine interdepartmental conferences were selected as the way for
      improvement in the accuracy of diagnosis. CONCLUSIONS: vast majority of cases
      evaluated at the OH are complex and difficult compared with the cases studied at
      a GHs.

PMID- 19744392
TI  - [Development of a position on sexuality in health care providers].
AB  - BACKGROUND: two attitudes were considered about sexual practice; one is centered
      in the reproduction, attaching to as a natural thing and intolerance to different
      expressions of sexuality. The other view according to prevent damage and sexual
      practices without guilt, bashful attitudes and intolerance. Our objective was to
      evaluate the effect of an educational intervention, upon the development of the
      position on sexuality in health care providers. METHODS: study of comparative
      intervention. Two experimental groups and one control group with initial and
      final measurements were used. To compare two groups we used the U tests of Mann
      Whitney and Kruskal-Wallis. RESULTS: the initial median of the experimental group
      1 (GE1) and the witness (GT) were equal and significantly different from the
      experimental group 2 (GE2); in this one, only 31% of its members initiated
      without position, as opposed to the 100% of the GE1, and of 93 % of the GT.
      CONCLUSIONS: a high proportion of health care providers had no posture on
      sexuality. A position was not reached with the accumulating information; it
      develops through the questioning of their experience, the educational perspective
      being an essential factor to achieving it.

PMID- 19744393
TI  - [Recurrent pericardial effusion due to familiar Mediterranean fever].
AB  - Pericarditis is usually a complication of viral or bacterial infection. In
      addition, it can be associated to systemic diseases such as autoimmune disorders,
      rheumatic fever, cancer, tuberculosis and AIDS. It can also be related to
      familial Mediterranean fever, an autosomic recessive inflammatory disease,
      characterized by fever, abdominal pain, and pleuritis mainly seen in persons from
      the Mediterranean area. In this study, we described the evolution and treatment
      response to colchicine in three patients with pericarditis associated to familial
      Mediterranean fever. Two of the patients had a pericardiectomy showing in their
      biopsy nonspecified inflammatory changes. Later their diagnosis were confirmed by
      genetic markers, echocardiogram and EKG. They were treated with antiviral and
      antibiotics without any improvement; subsequently they had good results with
      colchicine.

PMID- 19744394
TI  - [Two cases of Dyke-Davidoff-Masson syndrome and adult cerebral hemiatrophy].
AB  - BACKGROUND: cerebral hemiatrophy (CHA) can present in childhood or adulthood, if
      it presents before or after two years of age. This two entities differ in
      etiology, clinical presentation and imaging characteristics. The CHA of childhood
      or Dyke-Davidoff-Masson syndrome, is originated by intrauterine or perinatal
      insults that affect the perfusion of a single cerebral hemisphere, manifesting
      clinically by variable mental retardation, refractory epilepsy, facial asymmetry,
      hemiplegia/hemiparesis or abnormal movements of the contralateral extremities and
      by imaging studies, loss of volume in one cerebral hemisphere and ipsilateral
      compensatory cranial changes such as skull vault thickening, elevation of the
      orbital roof and petreous ridge, also hyperpneumatization of the frontal sinus
      and mastoid cells. Instead, the CHA of the adult is multifactorial and by imaging
      it only manifests as loss of volume in one cerebral hemisphere, without
      compensatory changes in the skull. CASES REPORT: we present a classic clinical
      case of CHA secondary to perinatal insult and another case of CHA of adulthood
      secondary to multiple embolic strokes in a patient with inactive rheumatic heart
      disease, commenting the imaging differences of these rare clinical entities.

PMID- 19744395
TI  - [A3243G mitochondrial DNA mutation and heterogeneous phenotypic expression].
AB  - BACKGROUND: mitochondrial DNA (DNAmt) mutations are associated with several
      clinical manifestations affecting different systems. They are usually
      underdiagnosed even with the relatively high prevalence in certain populations.
      The diagnosis can be established on clinical data, histopathologic studies and
      biochemical abnormalities in the respiratory chain, or the finding of the
      specific causal mutation in the DNAmt. CLINICAL CASE: we describe a patient and
      her family history, affecting neurologic, cardiovascular and endocrine systems.
      We established the diagnosis of MELAS syndrome (mitochondrial encephalomy-opathy,
      lactic acidosis and stroke-like episodes) with the collaboration of the
      Laboratory of Molecular Neurogenetics of the Department of Neurology of Columbia
      University in New York, NY, USA to whom we sent peripheral blood DNA. The DNA was
      amplified by polymerase chain reaction (PCR) and subjected to restriction
      fragment length polymorphism analysis. The study was positive for the point
      mutation adenine (A) for guanine (G) on the position 3243 of DNAmt. We make a
      brief clinical description. We also review DNAmt, related mutations and clinical
      expressions of the disease. We also highlighted the prevalence of DNAmt mutations
      in certain clinical situations.

PMID- 19744396
TI  - [How low is hypocholesterolemia and associated diseases? (Second participation)].

PMID- 19744397
TI  - [Thanatos and ethics: an approach from philosophy on facing death].
AB  - The paper is a reflection on an ethical proposal of death. Death is seen as a
      natural part in the process of life. There are different ideas focusing on the
      useless suffering in patients, physician's frustrations and unfair indignation
      from patients' families. Also questioned is the traditional way to understand the
      right to live versus the right to a life with quality, understanding the last as
      the most important. The article concludes with a critical point of view about
      euthanasia and its implications generated by health professionals in their daily
      practices.

PMID- 19744398
TI  - Management of restless legs syndrome augmentation.
AB  - Augmentation is the main complication of long-term dopaminergic treatment of
      restless legs syndrome (RLS). Although augmentation was first described in 1996
      and is characterized by an overall increase in severity of RLS symptoms (earlier
      onset of symptoms during the day, faster onset of symptoms when at rest,
      spreading of symptoms to the upper limbs and trunk, and shorter duration of the
      treatment effect), precise diagnostic criteria were not established until 2003.
      These criteria were updated in 2007 to form a new definition of augmentation
      based on multicenter studies. Augmentation should be differentiated from early
      morning rebound, natural progression of the disease, tolerance, and neuroleptic
      induced akathisia. Treatment strategies will depend on the degree of clinical
      significance but will be based on the use of longer-acting drugs and a reduction
      or substitution of the dopaminergic agents. The most effective preventive measure
      is to keep the dose of the dopaminergic medication as low as possible, ensuring
      that it does not exceed the dose recommended by regulatory authorities. RLS
      augmentation needs to be treated only if it is clinically relevant-that is, if it
      has a significant impact on the patient's daily activities. Mild cases should be
      followed closely, however. In severe cases, a change of treatment (sometimes even
      within the same class of drugs) can be effective, although before taking this
      step, it should be verified that all factors that may affect augmentation
      (changes in lifestyle, iron deficiency, serotonin reuptake inhibitors) have been
      excluded.

PMID- 19744399
TI  - Treatment of nocturnal eating disorders.
AB  - Identifying abnormal nocturnal eating is critically important for patient care
      and public health. Obesity is a global pandemic and a leading cause of
      preventable mortality in the United States, with more than 100,000 deaths
      annually. Normally, nighttime energy homeostasis is maintained, despite an
      absence of food intake, through appetite suppression and alterations in glucose
      metabolism that result in stable energy stores. Two conditions break this
      nighttime fast and are associated with weight gain as well as medical and
      neuropsychiatric comorbidities. Sleep-related eating disorder (SRED) is
      characterized by isolated nocturnal eating, whereas the night-eating syndrome
      (NES) is a circadian delay in meal timing leading to evening hyperphagia,
      nocturnal eating, and morning anorexia. Recently, SRED has been associated with
      the benzodiazepine receptor agonist zolpidem. Both SRED and NES are treatable and
      represent potentially reversible forms of obesity. In SRED, the antiseizure
      medication topiramate and dopaminergics have both demonstrated promising results.
      Nocturnal eating associated with NES has responded well to sertraline.

PMID- 19744400
TI  - Advances in treatment of obstructive sleep apnea syndrome.
AB  - The treatments for obstructive sleep apnea (OSA) described in this paper
      represent the latest information and data. Nasal continuous positive airway
      pressure, initially described in 1981, remains the cornerstone of therapy.
      Advances in mask interfaces, the use of humidification, the downloading of usage
      information, the development of pressure delivery modifications, and reductions
      in the size and noise of the machines have improved the devices over the past
      decade. Nevertheless, the basic premise of positive pressure delivery to splint
      the airway remains the primary driver of efficacy. Surgery for OSA, other than
      tracheostomy, has also been used for about the same period
      (uvulopalatopharyngoplasty was also initially described in 1981), but its
      efficacy has probably improved only marginally. The advances in surgical
      techniques have come through improved patient selection, minimally invasive
      techniques, and the performance of outcome studies. Surgery clearly remains a
      second-line or third-line therapy for moderate to severe OSA. Dental appliances
      were also introduced over two decades ago and clearly have become more mainstream
      in our treatment approach to OSA. Dental appliances are now considered a
      reasonable first-line therapy for mild OSA and perhaps even for some patients
      with moderate OSA. Custom-made appliances are clearly superior to those that
      cannot be adjusted, and in the hands of an experienced dentist or similarly
      trained expert, they are moderately successful for most patients. Among the newer
      therapies, transnasal insufflation and nasal expiratory resistance clearly have
      promise, again for patients with mild to moderate OSA. Further study may
      determine who will benefit from such modalities. No medications have been shown
      to have clinically significant efficacy, and drug treatment remains adjunctive.

PMID- 19744401
TI  - Treatment of sleep dysfunction and psychiatric disorders.
AB  - Patients with neurologic disorders commonly experience sleep dysfunction and
      psychiatric disorders. The most common sleep dysfunction is insomnia, which is a
      primary symptom in 30% to 90% of psychiatric disorders. Insomnia and fatigue are
      prominent symptoms of anxiety disorders and major depression that may occur in
      patients who are treated but have residual sleep dysfunction. Anxiety and
      depressive disorders account for 40% to 50% of all cases of chronic insomnia. It
      is also recognized that primary insomnia and other primary sleep disorders
      produce symptoms that are similar to those reported by patients with psychiatric
      disorders. A clinician must judge whether sleep deprivation causes mood
      disturbance or whether depressive or anxiety disorder represents the primary
      reason for sleep dysfunction. When insomnia is comorbid with mild to moderate
      depression, therapy should begin with bedtime dosing of sedating antidepressants
      such as mirtazapine, nefazodone, or tricyclic antidepressants, which are
      preferred because of their sedative effects. Often side effects limit their
      usefulness. Intervention for chronic insomnia is similar in nonpsychiatric and
      psychiatric patients. Behavioral therapies, particularly multicomponent cognitive
      behavioral therapy, and lifestyle changes show significant long-term efficacy as
      treatments for chronic insomnia. The most studied pharmacologic agents to treat
      insomnia are sedative hypnotic agents, particularly those that are active through
      the benzodiazepine receptor-GABA (gamma-aminobutyric acid) complex, such as
      benzodiazepines, eszopiclone, zaleplon, and zolpidem. Melatonin and the melatonin
      receptor agonist ramelteon have not had adequate study in psychiatric patients to
      define their use, but small studies suggest benefit. Prescription of adjunctive
      trazodone (50-150 mg) is a common clinical practice to treat comorbid insomnia
      during antidepressant therapy, but published data are surprisingly limited,
      considering its frequent use. Although there has been insufficient research on
      the use of atypical antipsychotic agents in severe insomnia, psychiatrists use
      quetiapine, olanzapine, or others to lessen agitation that disrupts sleep. When
      insomnia or hypersomnia continue even as mood, anxiety, or thought disorders
      improve with standard therapy, the physician should consider the potential
      presence of underlying sleep disorders.

PMID- 19744402
TI  - Treatment options for obstructive sleep apnea.
AB  - Sleep apnea is a major public health problem that afflicts 9% of women and 24% of
      men 30 to 60 years of age. It is highly treatable, but when untreated, it has
      been associated with (but not necessarily linked to) increased probability of
      cerebral and coronary vascular disease, congestive heart failure, metabolic
      dysfunction, cognitive dysfunction, excessive daytime sleepiness, motor vehicle
      accidents, reduced productivity, and decreased quality of life. The gold standard
      for treatment in adults is positive airway pressure (PAP) therapy: continuous PAP
      (CPAP), bilevel PAP, autotitrating CPAP, or autotitrating bilevel PAP. Measures
      to increase compliance with PAP therapy include medical or surgical treatment of
      any underlying nasal obstruction, setting appropriate pressure level and airflow,
      mask selection and fitting, heated humidification, desensitization for
      claustrophobia, patient and partner education, regular follow-up with monitoring
      of compliance software, and attendance of support groups (eg, AWAKE). Adjunctive
      treatment modalities include lifestyle or behavioral measures and pharmacologic
      therapy. Patients with significant upper airway obstruction who are unwilling or
      unable to tolerate PAP therapy may benefit from surgery. Multilevel surgery of
      the upper airway addresses obstruction of the nose, oropharynx, and hypopharynx.
      A systematic approach may combine surgery of the nose, pharynx, and hypopharynx
      in phase 1, whereas skeletal midface advancement or tracheotomy constitutes phase
      2. Clinical outcomes are reassessed through attended diagnostic polysomnogram
      performed 3 to 6 months after surgery. Oral appliances can be used for patients
      with symptomatic mild or moderate sleep apnea who prefer them to PAP therapy or
      for whom PAP therapy has failed or cannot be tolerated. Oral appliances also may
      be used for patients with severe obstructive sleep apnea who are unable or
      unwilling to undertake PAP therapy or surgery. For children, the main treatment
      modality is tonsillectomy and adenoidectomy, with or without turbinate surgery.
      Children with craniofacial abnormalities resulting in maxillary or mandibular
      insufficiency may benefit from palatal expansion or maxillary/mandibular surgery.
      PAP therapy may be used for children who are not surgical candidates or if
      surgery fails.

PMID- 19744403
TI  - New perspectives on assessment of suicide risk.
AB  - Concerns have arisen during recent years over a possible link between suicide and
      medications used to treat several medical conditions, including depression,
      asthma, epilepsy, and smoking. The concern over the safety of these medications
      was sparked by data from postmarketing and retrospective analyses of clinical
      trials. However, clinical trials were not initially designed to measure
      suicidality, and this methodologic limitation weakens the ability to make causal
      conclusions. Postmarketing results also have methodologic limitations (such as
      the absence of control groups) that limit the ability to make causal conclusions.
      Postmarketing results are also misleading because each of the medical conditions
      involved is highly comorbid with depression. The risk of not treating these
      conditions with an active and effective medication may clearly outweigh the
      possible slight elevation of the risk of suicidal thoughts and behaviors. The
      decision to take a medication should be made in consultation with a physician and
      based upon considerations of the risks and benefits of the medication. Physicians
      and the public need accurate information on the suicide risks associated with
      medications to make informed treatment decisions. The most effective way to
      ascertain the true risk (or lack of risk) associated with a medication is to
      systematically and prospectively assess suicidal thoughts and behaviors in
      randomized, placebo-controlled clinical trials. If a medication is scientifically
      determined to increase the risk for suicidal thoughts and behaviors, then the
      risk needs to be accurately translated and communicated to physicians and
      patients. Physicians prescribing these medications will need to closely monitor
      and assess their patients for changes in mood and suicide risk throughout
      treatment and must be able to recognize when a patient needs specialized mental
      health care. Mental status changes can be appropriately monitored and managed.
      Some medical conditions, such as asthma and epilepsy, and some treatment goals,
      such as smoking cessation, have inherent increased risks for depression-and by
      extension, suicide-that necessitate accurate, ongoing assessment.

PMID- 19744404
TI  - Current treatment options for depression after mild traumatic brain injury.
AB  - Mild traumatic brain injury (MTBI) is the most common neurologic condition in the
      United States; about 503 of every 100,000 persons visiting the emergency
      department have this diagnosis. A complex cluster of neurologic signs and
      symptoms are associated with an acceleration-deceleration mechanism of injury.
      Unfortunately, many persons do not seek treatment for MTBI. Depression following
      MTBI adds to the complexity and complicates the diagnosis and treatment because
      of overlap of symptoms, including delays in information processing, sleep
      difficulties, irritability, and fatigue, as well as pain in association with
      headache or other musculoskeletal injuries. Depression after MTBI has been
      associated with abnormal CT scan results, older age, and increased depressive
      symptoms within a week after injury. Given the progress made in understanding the
      natural history of MTBI and post-TBI depression in general, there has been less
      progress in treatment trials for post-MTBI depression. In this review, we report
      on one phase 4, nonrandomized single-group trial in persons with mild-to-moderate
      TBI and note a "response to treatment" effect without the ability to discern the
      potential impact of other prescribed pharmacotherapies on the outcome. In a
      randomized controlled trial focusing on a telephone counseling intervention for
      post-MTBI symptoms, the intervention appeared to be effective in reducing 6-month
      post-MTBI symptoms, but it was not effective for the general health outcome,
      which included measures of depressive symptoms and anxiety. Thus, evidence-based
      treatment of post-MTBI depression is quite limited. Because depressive symptoms
      can develop as early as 1 week after injury and can be exacerbated by stress,
      pain, and comorbidities, it seems prudent to begin early interventions focused on
      managing pain and stress, along with providing psychoeducational and problem
      solving therapies. Efficacy studies are needed to determine whether telemedicine
      approaches, group interventions, or peer counseling may be helpful methods of
      delivering such interventions during the early months as ways to attenuate the
      development of a major depressive disorder.

PMID- 19744405
TI  - Pharmacologic treatment of impulsive aggression with antiepileptic drugs.
AB  - Aggressive behavior is a major concern in mental health and criminal justice
      settings. Although pharmacotherapy is often used in the treatment of the violent
      individual, no medication is presently approved by the US Food and Drug
      Administration specifically for such use. In recent years, antiepileptic drugs
      (AEDs) have become increasingly popular for the management of impulsive
      (reactive) aggressive behavior. The research literature has implicated several
      neurobiologic deficits associated with impulsive aggression, including reduced
      central serotonergic functioning, executive dysfunction, and prefrontal deficits.
      It has been suggested that the neurobiologic deficits specific to impulsive
      aggressive behavior may serve as indicators of an ineffective behavioral control
      system. A review of the literature finds that AEDs, particularly those that block
      sodium channels and/or have GABA-related mechanisms of action, are effective in
      reducing the frequency and intensity of impulsive aggressive outbursts both when
      used as the primary agent of treatment and as an adjunct to ongoing
      pharmacotherapy. Strong evidence for efficacy in impulsive aggression exists from
      randomized controlled trials for most of the common AEDs (phenytoin,
      carbamazepine, oxcarbazepine, lamotrigine, valproate/divalproex sodium,
      topiramate). Additional controlled studies are needed for tiagabine and
      gabapentin. Of the common AEDs, only levetiracetam has been shown to be
      ineffective in the treatment of impulsive aggression. It is important to note
      that the anti-aggressive effects seen with the AEDs appear to be specific to the
      impulsive form of aggression. Individuals who display premeditated aggression do
      not seem to benefit from this type of treatment. Clinically, we recommend
      phenytoin (initial dose 100 mg three times daily) as the AED of first choice for
      the treatment of impulsive aggressive outbursts. This recommendation is based on
      this drug's limited side effect profile (compared with the other AEDs) and the
      large amount of empiric data supporting its clinical efficacy in impulsive
      aggression. In the event that the impulsive aggressive individual does not
      respond to pharmacotherapy with phenytoin, carbamazepine (initial dose 150 mg
      three times daily) and valproate/divalproex sodium (initial dose 250 mg three
      times daily) have both proved to be effective secondary options.

PMID- 19744406
TI  - Brain-derived neurotrophic factor and initial antidepressant response to an N
      methyl-D-aspartate antagonist.
AB  - OBJECTIVE: A model has been proposed to explain the pathophysiology of mood
      disorders based on decreased neurotrophin levels during mood episodes; treatment
      with antidepressants and mood stabilizers is associated with clinical
      improvement. This study investigated whether changes in brain-derived
      neurotrophic factor (BDNF) levels are associated with the initial antidepressant
      effects of ketamine, a high-affinity N-methyl-D-aspartate (NMDA) antagonist.
      METHOD: Twenty-three subjects aged 18 to 65 years with DSM-IV major depressive
      disorder (treatment resistant) participated in this study, which was conducted
      between October 2006 and May 2008. The subjects were given an open-label
      intravenous infusion of ketamine hydrochloride (0.5 mg/kg) and rated using
      various depression scales at baseline and at 40, 80, 120, and 230 minutes
      postinfusion. The primary outcome measure was the Montgomery-Asberg Depression
      Rating Scale score. BDNF levels were obtained at the same time points as
      depression rating scale scores. RESULTS: Despite a significant (P <. 001)
      improvement in MADRS scores after subjects received ketamine treatment, no
      changes in BDNF levels were observed in subjects after they received ketamine
      compared to baseline. Also, no association was found between antidepressant
      response and BDNF levels. CONCLUSIONS: This study demonstrates that ketamine's
      rapid initial antidepressant effects are not mediated by BDNF. Further studies
      are necessary to shed light on the neurobiological basis of these effects. TRIAL
      REGISTRATION: clinicaltrials.gov Identifiers: NCT00024635 and NCT00088699.

PMID- 19744407
TI  - What is hypomania? Tetrachoric factor analysis and kernel estimation of DSM-IV
      hypomanic symptoms.
AB  - BACKGROUND: The DSM-IV definition of hypomania, which relies on clinical
      consensus and historical tradition, includes several "nonspecific" symptoms. The
      aim of this study was to identify the core symptoms of DSM-IV hypomania. METHOD:
      In an outpatient private practice, 266 bipolar II disorder (BP-II) and 138 major
      depressive disorder (MDD) remitted patients were interviewed by a bipolar-trained
      psychiatrist, for different study goals. Patients were questioned, using the
      Structured Clinical Interview for DSM-IV, about the most common symptoms and
      duration of recent threshold and subthreshold hypomanic episodes. Data were
      recorded between 2002 and 2006. Four different samples, assessed with the same
      methodology, were pooled for the present analyses. Tetrachoric factor analysis
      was used to identify core hypomanic symptoms. Distribution of symptoms by kernel
      estimation was inspected for bimodality. Validity of core hypomania was tested by
      receiver operating characteristic (ROC) analysis. RESULTS: The distribution of
      subthreshold and threshold hypomanic episodes did not show bimodality.
      Tetrachoric factor analysis found 2 uncorrelated factors: factor 1 included the
      "classic" symptoms elevated mood, inflated self-esteem, decreased need for sleep,
      talkativeness, and increase in goal-directed activity (overactivity); factor 2
      included the "nonspecific" symptoms irritable mood, racing/crowded thoughts, and
      distractibility. Factor 1 discriminatory accuracy for distinguishing BP-II versus
      MDD was high (ROC area = 0.94). The distribution of the 5-symptom episodes of
      factor 1 showed clear-cut bimodality. Similar results were found for episodes
      limited to 3 behavioral symptoms of factor 1 (decreased need for sleep,
      talkativeness, and overactivity) and 4 behavioral symptoms of factor 1 (adding
      elevated mood), with high discriminatory accuracy. CONCLUSIONS: A core,
      categorical DSM-IV hypomania was found that included 3 to 5 symptoms, ie,
      behavioral symptoms and elevated mood. Behavioral symptoms (overactivity domain)
      could be the basic phenotype of hypomania. This finding could help in probing for
      hypomania and reduce misdiagnosis. Biologic research could focus more on the
      underpinnings of the overactivity domain specifically.

PMID- 19744410
TI  - Minor derm ailments: how good is the evidence for common treatments?
AB  - Oral flucloxacillin is less effective than local antibiotics for impetigo in
      limited disease. Topical metronidazole and azelaic acid are effective for
      rosacea. Betadine is effective for minor infections following partial thickness
      burns. Terbinafine is effective against fungal infections of the nail. Miconazole
      is effective against oral thrush.

PMID- 19744408
TI  - Medical comorbidity among youth diagnosed with bipolar disorder in the United
      States.
AB  - OBJECTIVE: This study examines the number and type of medical comorbidities among
      youth diagnosed with bipolar disorder. METHOD: This is a retrospective data
      analysis using the 2000-2001 Thomson Medstat MarketScan medical claims and
      administrative files. The population included a national sample of youth (ages 6
      18 years) from privately insured families within the United States. Number of
      chronic medical conditions and type of medical comorbidity were analyzed in ICD
      10-diagnosed youth with bipolar disorder (N = 832) and other types of psychiatric
      disorders (N = 21,493) using The Johns Hopkins Adjusted Clinical Groups Case Mix
      System, Version 8.0. RESULTS: Thirty-six percent of youth with bipolar disorder
      had 2 or more chronic health conditions versus 8% of youth with other psychiatric
      diagnoses. The following categories of medical conditions were significantly more
      prevalent in youth diagnosed with bipolar disorder: cardiology,
      gastrointestinal/hepatic, neurologic, musculoskeletal, female reproductive, and
      respiratory. Toxic effects and adverse events were also higher in youth with
      bipolar disorder, compared to youth with other psychiatric disorders.
      CONCLUSIONS: Youth with bipolar disorder experience higher rates of several
      medical illnesses compared to youth with other psychiatric diagnoses. Several
      factors may explain this phenomenon, including worse medication side effects,
      unhealthy lifestyle behaviors, poorer access to health care services,
      socioeconomic status, and biologic susceptibility. Moreover, a diagnosis of
      bipolar disorder may reflect more frequent health care utilization and therefore
      more opportunities for additional medical diagnoses. Further understanding
      regarding reasons for these relatively high rates of comorbidity among youth
      diagnosed with bipolar disorder may be helpful in improving overall health and
      quality of life during the early stages/onset of this disorder.

PMID- 19744411
TI  - Clinical inquiries. When is it OK for children to start drinking fruit juice?
AB  - Children should be at least 6 months of age and parents should provide only 100%
      fruit juice in a cup (not a bottle). Intake should be limited to 4 to 6 oz a day
      until 12 months of age. It's important to reiterate to parents that breastfeeding
      is the preferred source of infant nutrition for the first 6 (preferably 12)
      months of life. Sugar-sweetened fruit drinks have been linked to excess weight
      gain and obesity. Sugar-sweetened beverages provide little nutritional benefit to
      children and should be restricted.

PMID- 19744412
TI  - When an athlete can't catch his breath.
AB  - Don't rely on self-reported symptoms to diagnose exercise-induced
      bronchoconstriction (EIB). Indirect testing is the best way to diagnose EIB in
      patients who do not have underlying asthma. Short-acting beta2-agonists should be
      first-line management in EIB.

PMID- 19744413
TI  - Eye on the elderly. Hypertension care: striking the proper balance.
AB  - Treat systolic hypertension in the elderly to reduce their risk of cardiovascular
      events and mortality. Don't shy away from treating the very old. Hypertension
      treatment is beneficial even in patients who are 80 years of age or older. Don't
      prescribe an angiotensin-converting enzyme inhibitor and an angiotensin receptor
      blocker for elderly patients without heart failure; the combination increases the
      risk of adverse effects without reducing cardiovascular events.

PMID- 19744414
TI  - Eye on the elderly. Screening for hearing loss, risk of falls: a hassle-free
      approach.
AB  - Simply asking elderly patients whether they have trouble hearing is an effective
      start to screening for hearing loss. Refer elderly patients with suspected
      hearing impairment for audiologic diagnosis and nonmedical rehabilitation
      treatment, including hearing aids. To assess a patient's risk of falling, review
      gait, balance disorders, weakness, environmental hazards, and medications.

PMID- 19744415
TI  - Ovary-sparing hysterectomy: is it right for your patient?

PMID- 19744416
TI  - Pandemic and seasonal flu: what you need to know.

PMID- 19744417
TI  - A white spot since birth.

PMID- 19744418
TI  - Clinical inquiries. Which treatments work best for hemorrhoids?
AB  - Excision is the most effective treatment for thrombosed external hemorrhoids. For
      prolapsed internal hemorrhoids, the best definitive treatment is traditional
      hemorrhoidectomy. Of nonoperative techniques, rubber band ligation produces the
      lowest rate of recurrence.

PMID- 19744419
TI  - Clinical inquiries. How should you treat trochanteric bursitis?
AB  - Conservative measures--followed by corticosteroid injection, if necessary--are
      best. Conservative therapy includes rest, nonsteroidal anti-inflammatory drugs
      (NSAIDs), and stretching exercises focused on the lower back and sacroiliac
      joints. Patients whose symptoms persist despite conservative therapy are likely
      to benefit from an injection of 24 mg betamethasone and 1% lidocaine (or
      equivalent) into the inflamed bursa. In rare cases of intractable symptoms,
      surgical procedures such as iliotibial band release, subgluteal bursectomy, and
      trochanteric reduction osteotomy are options.

PMID- 19744420
TI  - Integrating HPV vaccination into your practice: overcoming common barriers.

PMID- 19744421
TI  - A checklist approach to selecting the optimal treatment regimen for a patient
      with type 2 diabetes.
AB  - T2DM is a multifaceted disease that requires careful selection of treatment,
      which must be frequently modified over the continuum of care to attain successful
      long-term management. A checklist of factors to be considered can be helpful in
      individualizing treatment for optimal effectiveness based on each patient's
      needs, concerns, and capabilities.

PMID- 19744422
TI  - Selecting among ADA/EASD tier 1 and tier 2 treatment options.
AB  - Each of the 4 groups of medications considered preferred therapies for treatment
      of T2DM by the ADA/EASD panel--insulin, sulfonylureas, TZDs, and incretin-based
      therapies (GLP-1 receptor agonists)--possesses significant advantages and
      disadvantages to be considered when individualizing treatment. Insulin and the
      sulfonylureas are the most researched therapies available, as well as the most
      cost-effective and the most effective in achieving glycemic goals. The TZDs have
      been shown to improve various markers of pancreatic beta-cell function; however,
      there is a risk of edema and heart failure with the TZDs; rosiglitazone has been
      associated with an increase in cardiovascular events. GLP-1 receptor agonists and
      DPP-4 inhibitors address different pathophysiologic causes than do other diabetes
      medications and offer the benefit of a low incidence of hypoglycemia. Moreover,
      GLP-1 receptor agonists promote weight loss, whereas DPP-4 inhibitors are
      generally weight neutral.

PMID- 19744423
TI  - Natural history of HPV infections.

PMID- 19744424
TI  - Practical applications of therapy with a glucagon-like peptide-1 receptor
      agonist.
AB  - Patients such as ML represent a common challenge in the primary care management
      of patients with T2DM. After some response to initial therapy with lifestyle
      management and metformin, the A1C goal of <7.0% after 2 to 3 months was not
      achieved, necessitating the initiation of combination therapy. The 4 groups of
      medications recommended by the ADA/EASD panel as the preferred therapies are
      basal insulin, the sulfonylureas, the TZD pioglitazone, and GLP-1 receptor
      agonists. In addition to considering efficacy, safety, cost, and other medication
      related factors, the treatment plan must take into account the patient's
      individual needs, concerns, and capabilities. These additional considerations
      help to foster increased patient self-management and greater treatment adherence.
      To achieve these objectives, comprehensive patient education is essential. The
      unique mechanism of action of the GLP-1 receptor agonist class of medications
      makes these agents a desirable choice as add-on therapy to metformin.

PMID- 19744425
TI  - Patient education and monitoring recommendations for the use of glucagon-like
      peptide-1 receptor agonists.
AB  - Ongoing patient education and feedback is critical to successful self-management
      for patients with T2DM. The patient's individualized program is based on an
      ongoing needs assessment, involves an interprofessional approach with a team of
      qualified health care professionals, and supports the patient by using positive
      feedback and motivational strategies at each visit.

PMID- 19744426
TI  - Atypical subacute thyroiditis.

PMID- 19744427
TI  - Cardiac paraganglioma presenting as gestational hypertension.

PMID- 19744428
TI  - Vaginal paraganglioma presenting as a pelvic mass.
AB  - Paragangliomas are extra-adrenal neuroendocrine neoplasms derived from neural
      crest precursors. These tumors rarely arise from the female genital tract.
      Vaginal paragangliomas are extremely rare. We describe a case of vaginal
      paraganglioma managed with minimally invasive surgical techniques.

PMID- 19744429
TI  - Sister Mary Joseph's nodule associated with hepatocellular carcinoma.

PMID- 19744430
TI  - Barium appendicitis.

PMID- 19744431
TI  - Presence of minute cancer cell dissemination in peritoneal lavage fluid detected
      by reverse transcription PCR is an independent prognostic factor in patients with
      resectable pancreatic cancer.
AB  - BACKGROUND: Presence of minute cancer cell dissemination in peritoneal lavage
      fluid detected by reverse transcription polymerase chain reaction (RT-PCR) has
      been reported to be a reliable predictor of the prognosis in several kinds of
      cancers, but has not been determined in pancreatic cancer. METHODS: Peritoneal
      lavage fluid was harvested just after a laparotomy in 83 patients with
      adenocarcinoma of the pancreas. Half of the fluid was examined by cytology and
      the remaining half was used to measure carcinoembryonic antigen/beta-2
      microglobulin (beta2M) mRNA expression. Patients were followed after surgery to
      evaluate its clinical significance. RESULTS: Among 83 patients, 3 were
      cytologically positive (CY+), while 23 were positive by RT-PCR (PCR+). Seventy
      one patients underwent a surgical resection whereas 12 were unresectable. Because
      2 were CY+ among the 71 operated patients, the remaining 69 CY- patients were
      further investigated. Among those 69 patients, PCR+ was observed in 15 patients,
      whose incidence of postoperative peritoneal recurrence was significantly higher
      than that in PCR- patients (21% vs 4% at 3 years; P = .039). Moreover, both the
      recurrence-free rate in the abdominal cavity (peritoneal or local recurrence,
      excluding liver metastases) and the overall survival rate were better in PCR-
      patients than PCR+ patients (78% vs 33%, P = .0045 and 67% vs 46%, P = .0151). A
      multivariate analysis revealed positive lymph node metastases (hazard ratio;
      5.18) and positive RT-PCR (hazard ratio; 3.65) were independent prognostic
      factors. CONCLUSION: The RT-PCR-based cancer cell detection was an independent
      prognostic factor in patients with resectable adenocarcinoma of the pancreas and
      had close association with local or peritoneal recurrence.

PMID- 19744432
TI  - Prognostic implications of tumor invasion or adhesion to peripancreatic vessels
      in resected pancreatic cancer.
AB  - BACKGROUND: The purpose of this study was to evaluate the operative risk and the
      prognostic implications of pancreatectomy plus resection and reconstruction of
      peripancreatic vessels (PPV) in patients with pancreatic adenocarcinoma. METHODS:
      One hundred ten patients who underwent pancreatectomy with PPV resection and
      reconstruction (Study Group; SG) were retrospectively compared with 62 patients
      without distant metastasis who were palliated, (Control Group 1; CG-1), as well
      as 197 patients who underwent "conventional"pancreatectomy (Control Group 2; CG
      2). RESULTS: Postoperative morbidity and mortality were similar in SG (33% and
      3%), in CG-1 (26% and 3%), and in CG-2 (40% and 6%) patients. Median survival
      time (MST) of SG patients (15 months) was longer than that of CG-1 patients (6
      months; P < .0001) and similar to that of CG-2 patients (18 months). Patients
      undergoing isolated venous resection (n = 84) had the best outcome (MST: 15
      months) ( P < .0001 vs CG-1 patients), while patients undergoing resection of
      multiple PPV (n = 14) had the worst outcome (MST: 8 months). PPV infiltration,
      histologically proven in 64 patients (65%), was associated with decreased MST
      only if the tunica intima was infiltrated (26%) (11 months; P < .001).
      Multivariate analysis showed that no adjuvant therapy, intimal invasion, and
      poorly differentiated histology were associated with a higher hazard of death by
      2.2, 2.2, and 2.5-fold, respectively. CONCLUSION: In properly selected patients,
      pancreatectomy plus resection and reconstruction of PPV was performed as safely
      as palliation or "conventional" pancreatectomy and was associated with better
      survival when compared to palliation.

PMID- 19744433
TI  - Carcinoma erysipeloides in breast cancer.

PMID- 19744434
TI  - Evaluation of long-term results and recurrent factors after operative and
      nonoperative treatment for hepatolithiasis.
AB  - BACKGROUND: Hepatolithiasis is a common disease in East Asia. Operative and
      nonoperative procedures for the management of hepatolithiasis have been
      discussed, but long-term follow-up results of such treatments are only reported
      rarely. We evaluated the long-term results of operative and nonoperative
      treatments and examined risk factors for the recurrence of stones or cholangitis.
      METHODS: We conducted a retrospective study of case records of patients with
      hepatolithiasis who underwent treatment by operative therapy or nonoperative
      percutaneous transhepatic cholangioscopy (PTCS), or peroral cholangioscopy. Of
      311 patients with hepatolithiasis, 236 underwent follow-up after operative (n =
      90), PTCS (n = 97), or peroral cholangioscopy (n = 49) treatment. RESULTS:
      Complete stone clearance was achieved in 83.3% of hepatectomy, 63.9% of PTCSL,
      and 57.1% of peroral cholangioscopy patients. After a median follow-up period of
      8.0 years (up to 37 years), we observed stone recurrence in 30.9% (73/236) of
      patients, secondary biliary cirrhosis in 8.5% (19/224), late development of
      cholangiocarcinoma in 4.8% (11/227), and a mortality rate of 8.1% (19/236).
      Stricture, stones in both lobes, and nonoperative treatments were significant
      risk factors for incomplete stone clearance on multivariate analysis. In
      addition, recurrent stones and/or cholangitis were associated with nonoperative
      therapy (hazard ratio [HR], 2.01; 95% confidence interval [CI], 1.10-3.65),
      biliary cirrhosis (HR, 2.22; 95% CI, 1.24-3.98), residual stones (HR, 1.98; 95%
      CI, 1.24-3.17), and stricture (HR, 1.86; 95% CI, 1.01-3.43). CONCLUSION: In this
      long-term follow-up study, nonoperative therapy, biliary cirrhosis, residual
      stones, and biliary stricture were associated with recurrent stones and/or
      cholangitis after treatment.

PMID- 19744435
TI  - Pancreatic-pleural fistula is best managed by early operative intervention.
AB  - BACKGROUND: Pancreatic-pleural fistula is an uncommon complication of chronic
      pancreatitis occurring as a result of disruption of the main pancreatic duct and
      tracking of pancreatic fluid through the retroperitoneum into 1 or both thoracic
      cavities. The optimal treatment strategy for pancreatic-pleural fistula is
      unknown; it has traditionally been medical management followed by operative
      therapy for patients who fail to respond to conservative treatment. Our objective
      was to compile the case reports of pancreatic-pleural fistula in the literature
      in order to better define clinical management strategy. METHODS: The case
      management of pancreatic-pleural fistula was reviewed and a structured MEDLINE
      search for published studies was performed. Descriptive statistical analysis was
      performed on compiled data. RESULTS: Review of the literature revealed 63 adult
      patients with pancreatic-pleural fistula published in English between 1970 and
      2008. The majority of patients were male (71%) and there was a predominance of
      alcohol-associated chronic pancreatitis (51%). There were 10 complications (16%)
      and 2 deaths (3%) reported. Most patients were treated initially with medical
      therapy (87%). Medical therapy was deemed to have failed after an average period
      of 35+/-5 days. Total duration of therapy for patients in whom operative
      intervention was required after attempted medical management was 40+/-6 days,
      which was greater than the surgery alone cohort. In total, operative treatment
      was successful more often than medical therapy (94% vs 31%). CONCLUSION: Analysis
      from this series indicates that a majority of patients recover from pancreatic
      pleural fistula without sequelae (81%). Attempts at prolonged periods of medical
      therapy tend to delay the resolution of the fistula compared with patients who
      undergo definitive operative intervention early in the course of treatment.

PMID- 19744436
TI  - Identification of traumatic, right-sided diaphragm rupture in a patient with
      newly diagnosed situs inversus.

PMID- 19744437
TI  - WITHDRAWN: Pseudo-aneurysm of the cystic artery: A life-threatening cause of
      hemobilia after cholecystectomy.

PMID- 19744438
TI  - Whole or parts--the fate of hemoperitoneum.

PMID- 19744439
TI  - Anal leiomyoma.

PMID- 19744440
TI  - Gastric perforation from potential primary digestive aspergillosis.

PMID- 19744441
TI  - Chronic recurrent crampy abdominal pain owing to partial intestinal malrotation.

PMID- 19744442
TI  - Giant colonic lipoma.

PMID- 19744443
TI  - Immunoglobulin G4-associated cholangitis.

PMID- 19744444
TI  - An adrenal mass.

PMID- 19744445
TI  - Temporary intravascular shunting improves survival in a hypothermic traumatic
      shock swine model with superior mesenteric artery injuries.
AB  - BACKGROUND: Repairs of superior mesenteric artery (SMA) injuries are difficult
      and often result in high mortality. Our group has employed temporary
      intravascular shunts (TIVS) as a damage control procedure in a SMA transection
      model and hypothesized that TIVS would improve survival when compared with
      primary vascular anastomosis in the setting of a damage control surgery. METHODS:
      The SMA was clamped and completely transected while pigs were hemorrhaged to a
      mean arterial pressure of 40 mmHg and maintained in shock for 30 minutes. Cold
      lactated Ringer's solution was gradually infused while the abdomen was open to
      induce hypothermia. Animals were randomized to control (no resuscitation),
      primary anastomosis (PA), or temporary shunting (TS) of the SMA. Animals were
      resuscitated for 6 hours with the shed blood and lactated Ringer's solution.
      Delayed anastomosis was performed in TS animals after resuscitation. Surviving
      animals were humanely killed 2 days after operation. Systemic hemodynamic
      parameters were recorded hourly. The ileum was harvested at the end of
      resuscitation and experiment for pathologic evaluation. RESULTS: All animals
      suffered extreme physiologic conditions: hypothermia, severe acidosis,
      hypotension, and depressed cardiac output and oxygen delivery. Control animals
      suffered 100% mortality. Compared with the PA group, TS animals required less
      resuscitation fluid, retained higher SMA flow rates, normalized lactate levels
      faster, suffered less severe intestine histopathology, and had greater early
      survival. CONCLUSION: Damage control surgery in the setting of SMA transection
      seems better managed with TS than with PA. Further validation of this model is
      required before generalization to human applications.

PMID- 19744446
TI  - Natural orifice translumenal endoscopic surgery (NOTES): is it time for
      introduction to clinical practice?

PMID- 19744447
TI  - Spontaneous intramural duodenal hematoma complicating acute pancreatitis.

PMID- 19744448
TI  - Ocular melanoma metastatic to the pancreas after a 28-year disease-free interval.

PMID- 19744449
TI  - Exodus of Kampo, traditional Japanese medicine, from the complementary and
      alternative medicines: is it time yet?

PMID- 19744450
TI  - Celiac axis resection for extragastrointestinal stromal tumor.

PMID- 19744451
TI  - Folkert O. Belzer and the "hot dog experiment".

PMID- 19744452
TI  - Securing of tracheostomy tube using detachable clip in patients requiring neck
      wound management after esophageal, pharyngeal, and supinal surgery.

PMID- 19744453
TI  - Gallbladder carcinoma manifesting as acute cholecystitis: clinical and computed
      tomographic features.
AB  - BACKGROUND: Gallbladder carcinoma is uncommon and may manifest as acute
      cholecystitis. An accurate diagnosis is helpful for operative planning and this
      study attempted to explore the distinctive clinical and computed tomographic (CT)
      features for differentiating acute cholecystitis alone from that with
      contemporaneous gallbladder carcinoma. METHODS: This 20-year, retrospective study
      evaluated the CT features of 26 patients with surgically proven gallbladder
      carcinoma with clinical presentations of acute cholecystitis (carcinoma group).
      Thirty elderly patients with surgically proven simple acute cholecystitis were
      enrolled as age-matched controls (cholecystitis group). The clinical, laboratory,
      and CT findings were compared between the 2 groups. RESULTS: The carcinoma and
      cholecystitis groups showed no significant differences with respect to clinical
      symptoms (abdominal pain, fever, and jaundice), serum total bilirubin level,
      leukocyte count, percentage of segmented leukocytes, presence of gallstones, and
      CT features of pericholecystic stranding/fluid and focally increased enhancement
      of adjacent liver. Fifteen of the 26 (57.6%) patients in the carcinoma group
      exhibited diffuse gallbladder wall thickening on CT and the other 11 exhibited
      focal thickening or intraluminal masses. Beside female predominance, the patients
      in the carcinoma group had significantly higher serum aspartate/alanine
      aminotransferase and alkaline phosphatase levels, a thicker gallbladder wall,
      smaller volume, lower frequency of triple-layer gallbladder wall enhancement
      pattern, and a higher frequency of enlarged regional lymph nodes than those in
      the cholecystitis group. CONCLUSION: For elderly patients, especially women,
      presenting with acute cholecystitis and abnormal liver function, CT demonstration
      of focal gallbladder wall thickening, intraluminal masses, small gallbladder with
      diffuse wall thickening, and enlarged regional lymph nodes are suggestive of
      concurrent gallbladder carcinoma. Triple-layer gallbladder wall enhancement is
      suggestive of simple acute cholecystitis.

PMID- 19744454
TI  - Unique features of esophagogastric junction pressure topography in hiatus hernia
      patients with dysphagia.
AB  - BACKGROUND: Our aim was to assess pressure dynamics within the esophagogastric
      junction (EGJ) in sliding hiatus hernia (HH) during normal peristalsis and to
      compare the pressure profiles of HH patients with gastroesophageal reflux disease
      (GERD) symptoms (HH-GERD) to HH patients with dysphagia (HH-dysphagia). METHODS:
      High-resolution manometry studies in 230 consecutive patients and 68 controls
      were reviewed. HH patients were defined by a >or=1.5 cm separation between the
      lower esophageal sphincter (LES) and crural diaphragm (CD) on pressure topography
      plots. The HH population was further culled to eliminate those patients with
      motor disorders or stricture. The study groups were composed of 18 HH patients
      with only reflux symptoms and 10 HH patients with only dysphagia. Analysis of the
      pressure dynamics within the EGJ was performed at rest and after swallowing to
      independently quantify the LES and CD contributions to residual EGJ pressure, as
      well as the magnitude and genesis of distal esophageal intrabolus pressure (IBP).
      Differences among study groups were analyzed with analysis of variance. RESULTS:
      After swallows, HH-dysphagia patients had greater residual CD pressure (9 mmHg;
      standard deviation [SD], 4) and IBP pressure (19 mmHg; SD, 4) compared to HH-GERD
      patients (5 mmHg; SD, 2; and 12 mmHg; SD, 2, respectively; P<.001) or normal
      subjects (NA; 11 mmHg; SD, 3; P<.001). CONCLUSION: Sliding HH alters the pressure
      dynamics through the EGJ and can lead to a functional obstruction. Patients with
      HH and dysphagia have greater pressures through the CD compared to HH patients
      with GERD symptoms, supporting the hypothesis that sliding HH in and of itself
      may be responsible for dysphagia.

PMID- 19744455
TI  - Clinical validation and risk factors for delayed gastric emptying based on the
      International Study Group of Pancreatic Surgery (ISGPS) Classification.
AB  - BACKGROUND: Delayed gastric emptying (DGE) is one of the most common
      complications after pancreatoduodenectomy (PD). Because an objective, universally
      accepted definition of DGE does not yet exist, it is impossible to compare
      complication rates and outcomes of new operative approaches, operative
      techniques, and clinical trials. The International Study Group of Pancreatic
      Surgery (ISGPS) has proposed a universal classification for DGE based on clinical
      outcomes, but this classification has not been tested rigorously and applied to
      clinical data. Therefore, the aim of this study was to analyze our experience and
      to identify predictive factors for DGE by applying the ISGPS classification at a
      high-volume hospital. METHODS: From October 2002 to December 2007, 129
      consecutive patients underwent PD at the Department of Surgery, Yonsei University
      Medical Center. The severity of DGE was determined according to the ISGPS
      classification, and risk factors were evaluated retrospectively. RESULTS: The
      overall incidence of DGE was 33.3%, with 16 (12.4%) patients having grade A, 14
      (10.9%) grade B, and 13 (10.1%) grade C. Clinical outcomes worsened progressively
      as clinical relevant DGE increased. In multivariate analysis, clinically relevant
      pancreatic fistula (grade B/C) and patients with benign pathology were identified
      as independent factors for DGE. CONCLUSION: Pancreatic leakage is a serious
      complication after PD and is also associated with DGE. The ISGPS classification
      is a clear and useful tool to assess clinical outcomes.

PMID- 19744456
TI  - Tissue-type plasminogen activator prevents abscess formation but does not affect
      healing of bowel anastomoses and laparotomy wounds in rats with secondary
      peritonitis.
AB  - BACKGROUND: Intra-abdominal application of recombinant tissue-type plasminogen
      activator (rtPA) can decrease the rate of abscess formation in a rat peritonitis
      model. Before using rtPA clinically, its effects on healing of bowel anastomoses
      and laparotomy wounds should be investigated. METHODS: Peritonitis was induced in
      148 male Wistar rats via intra-abdominal injection of a feces/bacteria mixture.
      Laparotomy, operative debridement and construction of a colo-colostomy after a
      limited colectomy or ileo-ileostomy after a limited ileal resection were
      performed after 1 hour. All animals received antibiotics (ceftriaxone plus
      metronidazole). In addition to untreated controls, other animals received rtPA in
      1 of 3 dosing schemes, starting immediately after operation or 24 hour
      afterwards. Wound strength and hydroxyproline content of the wound were analyzed
      after 3 or 7 days. RESULTS: Mortality was 2% and manifestations of excessive
      bleeding were virtually absent. RtPA significantly decreased the rate of abscess
      formation. Neither bursting pressure nor breaking strength of the anastomoses was
      affected by any of the rtPA protocols. The same was true for wound strength in
      the abdominal fascia. Additionally, wound hydroxyproline content and architecture
      remained unchanged after rtPA administration. CONCLUSION: Intraperitoneal rtPA
      administration consistently and significantly decreased the rate of abscess
      formation, but did not affect wound healing. Clinical studies investigating its
      potential as an adjunct in the treatment of secondary peritonitis may be
      warranted.

PMID- 19744457
TI  - Long-term outcome of "prophylactic therapy" for familial medullary thyroid
      cancer.
AB  - BACKGROUND: About one quarter of all medullary thyroid cancers (MTC) are
      determined genetically due to a mutation in the RET proto-oncogene. The most
      common site of mutation is in codon 634. Therapeutic approaches toward patients
      at risk for the development of MTC identified by family screening programs range
      from total thyroidectomy to total thyroidectomy with lymphadenectomy of all 4
      compartments. METHODS: We report 17 patients (median age, 13 years; range, 4-36)
      carrying a mutation in codon 634 of the RET proto-oncogene who were operated on
      prophylactically at our department. All patients underwent thyroidectomy with
      bilateral cervicocentral lymphadenectomy. Current calcitonin level, overall
      survival, and disease-free survival were analyzed by contacting general
      practitioners and patients. RESULTS: Tumor classification was as follows: C-cell
      hyperplasia, 18% (n = 3); T1 (<1 cm), 71% (n = 12); and T1 (>1 cm), 12% (n = 2).
      Only 2 patients had lymph node metastases (12%). These patients developed
      recurrent disease (median observation time, 147 months; range, 90-181). In 1
      patient, the calcitonin level normalized after unilateral cervicolateral
      lymphadenectomy. The other patient (9 years old at primary operation) still has a
      persistently increased serum calcitonin level after 140 months of follow-up
      despite several operations for MTC. CONCLUSION: Total thyroidectomy with
      bilateral cervicocentral lymphadenectomy is sufficient as routine "prophylactic
      therapy" for patients with mutations in codon 634 of the RET proto-oncogene.
      Cervicolateral lymphadenectomy is indicated if calcitonin remains elevated after
      primary surgery. Prophylactic thyroidectomy should be performed before the
      development of lymph node metastases.

PMID- 19744458
TI  - Anatomic resection of segment VIII of liver for hepatocellular carcinoma in
      cirrhotic patients based on an intrahepatic Glissonian approach.
AB  - BACKGROUND: Isolated segmentectomy VIII is a technically demanding operative
      procedure and is reported only rarely. To our knowledge, no reports on anatomic
      segmentectomy based on an intrahepatic approach have been described. For
      cirrhotic patients with hepatocellular carcinoma (HCC) limited to segment VIII,
      this is a parenchyma-preserving hepatectomy that can be tolerated. METHODS:
      Eighteen patients with HCC underwent anatomic segment VIII segmentectomy from
      January 2005 to January 2008 in our institution. The operative techniques,
      postoperative, and oncologic outcomes were reviewed. RESULTS: Anatomic
      segmentectomy VIII was feasible with the technology described herein in all
      patients. The perioperative and oncologic outcomes were comparable with those of
      other similar hepatic resections. The median follow-up time was 28 months. The 3
      year survival rate was 65%. CONCLUSION: Although complex and technically
      demanding, an intrahepatic Glissonian approach for anatomic segmentectomy of
      segment VIII is an oncologically radical but parenchyma-sparing hepatic
      resection. In terms of preserving greater functioning liver parenchyma, it may be
      a safe and effective alternative to extensive hepatectomy.

PMID- 19744459
TI  - Reciprocal gut-brain evolutionary symbiosis provokes and amplifies the postinjury
      systemic inflammatory response syndrome.

PMID- 19744460
TI  - Vascular endothelial growth factor-D is correlated with hepatic metastasis from
      gastric cancer after radical gastrectomy.
AB  - BACKGROUND: Vascular endothelial growth factor-D (VEGF-D), the activating ligand
      for vascular endothelial growth factor receptor-3 (VEGFR-3), has been identified
      as an important endogenic tumor-associated lymphangiogenic factors which can
      promote lymphatic metastasis from primary tumor. Lymphatic metastasis, which is
      the most common metastatic method of gastric cancer (GC), is still deemed a
      potentially relative indicator of distant metastasis from GC. We hypothesize that
      VEGF-D is associated with hepatic metastasis (HM) from GC after radical
      gastrectomy by promoting lymphatic metastasis and/or hematogenous metastasis.
      METHODS: This study included 150 GC patients who underwent radical gastrectomy
      (75 cases presented with HM and 75 cases presented without any recurrences). VEGF
      D, VEGF-C, VEGF-A, VEGFR-2, VEGFR-3, and microvessel density (MVD) were evaluated
      by immunohistochemistry. Besides, clinicopathologic variables and prognosis of GC
      patients were analyzed statistically. RESULTS: Significant associations were seen
      between Lauren classification and HM, VEGF-D and HM, VEGFR-3 and HM, MVD and HM,
      and between nodal status and HM. VEGF-D remained an independent factor for HM
      from GC after radical gastrectomy. Further significant association was evaluated
      between high-grade VEGF-D expression and short disease-free survival of HM from
      GC after radical gastrectomy. CONCLUSION: VEGF-D, which can induce
      lymphangiogenesis specifically in many kinds of malignant diseases, is an
      important factor for predicting HM from GC following radical gastrectomy.

PMID- 19744461
TI  - Thyroid surgery in octogenarians is associated with higher complication rates.
AB  - BACKGROUND: The incidence of thyroid nodules increases with age and little
      information is available regarding the risks of thyroid surgery in elderly
      patients. The aim of this study was to determine whether thyroid surgery in
      patients > or =80 is associated with higher complication rates. METHODS: Out of
      3,568 patients undergoing thyroid surgery between July 2001 and October 2007 at a
      single institution, the records of 90 consecutive patients > or =80 years were
      reviewed retrospectively and compared with a cohort of 242 randomly selected
      patients aged 18-79, who underwent thyroid surgery during the same time period.
      Clinical variables included age, gender, pre-operative diagnosis, substernal
      component, previous surgery, final pathology, length of stay, comorbidities,
      American Society of Anesthesiologists (ASA) score, body mass index, postoperative
      complications, and mortality. RESULTS: Preoperative indications for surgery
      included benign disease in 51% vs 39%, suspected malignancy in 19% vs 26%, and
      suspected follicular neoplasms in 30% vs 35% in the octogenarian patient group (>
      or =80 years old) vs the younger patient cohort (P = NS). Octogenarians had 20%
      significant malignancy on final pathology vs 27% in the younger cohort (P = NS).
      The overall complication rate in the octogenarian group was 24% vs 9% in the
      younger cohort (P < .001). Male gender and ASA > or =3 were found to be
      independent risk factors for perioperative complications after thyroid surgery,
      while age alone was not. CONCLUSION: Age > or =80 is associated with higher
      morbidity after thyroid surgery, although not independently. Earlier operative
      intervention may be advised in those at high risk for disease progression,
      whereas follow-up strategies without operation may be advised for others.

PMID- 19744462
TI  - Technique of right hemihepatectomy preserving ventral right anterior section
      guided by area of hepatic venous drainage.
AB  - BACKGROUND: Although the consequences of partial venous outflow interruption have
      attracted only limited attention in liver surgery, maximal preservation of liver
      function after hepatic resection requires preservation of circulation in the
      remnant liver, especially hepatic vein drainage. METHODS: Data from 30 patients
      undergoing 3-dimensional imaging were analyzed to clarify the relationship
      between the area of the ventral right anterior section (RAS) and that drained by
      regional hepatic vein tributaries. The feasibility of our preliminary technique
      of right hemihepatectomy preserving the ventral RAS also was evaluated. RESULTS:
      The median estimated volume of the ventral RAS was 230 mL (range, 88-391). The
      average ratio of this estimated volume of the ventral RAS to total estimated
      liver volume was 18.0 +/- 4.9%. The median volume of the territory served by
      middle hepatic vein (MHV) tributaries draining the ventral RAS, expressed as a
      percentage of the whole volume of the ventral RAS, was 82.5%. Findings in fusion
      images of portal and hepatic vein territories demonstrated an area of MHV
      tributaries comparable with the ventral RAS area in 73.3% of all cases. As for
      the results of right hemihepatectomy with the ventral RAS preserved, no tumor was
      exposed on transection surfaces, and no recurrence took place within the
      preserved ventral RAS of the remnant liver. CONCLUSION: Procedures considering
      the importance of regional venous drainage offer the possibility of reducing the
      extent of surgery without loss of effectiveness.

PMID- 19744463
TI  - Characterization of antimicrobial resistance and integrons among Escherichia coli
      isolated from animal farms in Eastern China.
AB  - A total of 182 Escherichia coli isolates from animals, environment and workers of
      dairy cattle, swine and chicken farms in Shandong which locates in Eastern China,
      were investigated for antimicrobial resistance as well as prevalence and the
      transfer mechanisms of integrons. The results revealed isolates from swine and
      chicken farm exhibited high levels of resistance to antimicrobial agents. The
      positive rate of gene cassette of class 1 integron in dairy cattle, swine and
      chicken farms was 5%, 20% and 41.94%, respectively. Only four isolates possessed
      class 2 integron, all of which were from chicken farm. Nine distinct cassette
      arrays were detected and two novel gene cassette arrays yheSDelta-yheR-kefBDelta
      and chrADelta-sul1-qacEDelta1-orf5-aadA5-dfrA17 were identified in class 1
      integron for the first time. Class 1 integrons were found to be located mostly in
      both chromosomal and conjugative plasmid through southern hybridization and
      conjugation. PFGE revealed clonal relatedness among the isolates from different
      sources, especially within the same farm. The results confirmed the antimicrobial
      resistance and prevalence of integrons were strongly associated with the
      selection pressure of antimicrobial agents, and resistance genes in animal farms
      were probably spread by both vertical and horizontal transfer.

PMID- 19744464
TI  - Study of cystic echinococcosis in slaughtered animals in Al Baha region, Saudi
      Arabia: interaction between some biotic and abiotic factors.
AB  - The variation in cystic echinococcosis (CE) prevalence and mean intensity was
      studied in relation to site, season and host age and sex. A total of 12,911
      slaughtered animals, 140 camels, 2668 cattle, 6525 sheep and 3578 goats were
      inspected for hydatid cysts in Al Baha region, Saudi Arabia, in three study areas
      during four seasons from June 2008 to May 2009. The prevalence of infection was
      32.85%, 8.28%, 12.61% and 6.56% in camels, cattle, sheep and goats respectively.
      The prevalence of the parasite varied significantly in relation to site, season
      and host age classes and sex in most host species. Spring showed the highest
      prevalence in camels, cattle and sheep. A significant association was found among
      host age classes and likelihood of infection in all examined hosts and the oldest
      age class was significantly more likely to be infected. The main effects in
      parasite intensity were host sex and age in most examined host species. A
      positive correlation was found between intensity of CE and host age class in all
      animal species examined. The most commonly infected organs were liver and lungs
      which constituted 48.75% and 32.83% respectively, of the total infected organs.
      There was a significant difference among host species in fertile cysts
      (P<0.0001). The higher percentages of fertile cysts were in sheep (47.67%) and
      goats (23.99%) indicating that sheep and goats are the most important
      intermediate hosts for Echinococcus granulosus. Examined hydatid cysts of the
      liver had a higher fertility rate (38.79%) than those of the lungs (25.13%).
      Cysts size ranged from 1 to 8cm in diameter. The mean cyst diameter was found in
      the lungs higher than that in the liver in all hosts. The range in the number of
      cysts was 1-33 in infected animals. The mean number of cysts was higher in lungs
      than that in liver in all examined animals. The viability rate of protoscoleces
      of liver fertile cysts (62.20%) was significantly higher than that of lung cysts
      (52.73%). In conclusion, these findings of infection, mean abundance and
      fertility rates of CE in slaughtered animals, prompt plans for further
      epidemiological studies and control programmes.

PMID- 19744465
TI  - Energetic performance is improved by specific activation of K+ fluxes through
      K(Ca) channels in heart mitochondria.
AB  - Mitochondrial volume regulation depends on K+ movement across the inner membrane
      and a mitochondrial Ca2+-dependent K+ channel (mitoK(Ca)) reportedly contributes
      to mitochondrial K+ uniporter activity. Here we utilize a novel K(Ca) channel
      activator, NS11021, to examine the role of mitoK(Ca) in regulating mitochondrial
      function by measuring K+ flux, membrane potential (DeltaPsi(m)), light
      scattering, and respiration in guinea pig heart mitochondria. K+ uptake and the
      influence of anions were assessed in mitochondria loaded with the K+ sensor PBFI
      by adding either the chloride (KCl), acetate (KAc), or phosphate (KH2PO4) salts
      of K+ to energized mitochondria in a sucrose-based medium. K+ fluxes saturated at
      approximately 10 mM for each salt, attaining maximal rates of 172+/-17, 54+/-2.4,
      and 33+/-3.8 nmol K+/min/mg in KCl, KAc, or KH2PO4, respectively. NS11021 (50 nM)
      increased the maximal K+ uptake rate by 2.5-fold in the presence of KH2PO4 or KAc
      and increased mitochondrial volume, with little effect on DeltaPsi(m). In KCl,
      NS11021 increased K+ uptake by only 30% and did not increase volume. The effects
      of NS11021 on K+ uptake were inhibited by the K(Ca) toxins charybdotoxin (200 nM)
      or paxilline (1 microM). Fifty nanomolar of NS11021 increased the mitochondrial
      respiratory control ratio (RCR) in KH2PO4, but not in KCl; however, above 1
      microM, NS11021 decreased RCR and depolarized DeltaPsi(m). A control compound
      lacking K(Ca) activator properties did not increase K+ uptake or volume but had
      similar nonspecific (toxin-insensitive) effects at high concentrations. The
      results indicate that activating K+ flux through mitoK(Ca) mediates a beneficial
      effect on energetics that depends on mitochondrial swelling with maintained
      DeltaPsi(m).

PMID- 19744466
TI  - Quantification of Randomly-methylated-beta-cyclodextrin effect on liposome: an
      ESR study.
AB  - In the present work, the effect of Randomly-methylated-beta-cyclodextrin (Rameb)
      on the microviscosity of dimyristoyl-l-alpha phosphatidylcholine (DMPC) bilayer
      was investigated using the electron spin resonance (ESR) technique. The ability
      of Rameb to extract membrane cholesterol was demonstrated. For the first time,
      the percentage of cholesterol extracted by Rameb from cholesterol doped DMPC
      bilayer was monitored and quantified throughout a wide Rameb concentration range.
      The effect of cholesterol on the inner part of the membrane was also investigated
      using 16-doxyl stearic acid spin label (16-DSA). 16-DSA seems to explore two
      different membrane domains and report their respective microviscosities. ESR
      experiments also establish that the presence of 30% of cholesterol in DMPC
      liposomes suppresses the jump in membrane fluidity at lipids phase-transition
      temperature (23.9 degrees C).

PMID- 19744467
TI  - Suppression of Met activation in human colon cancer cells treated with (-)
      epigallocatechin-3-gallate: minor role of hydrogen peroxide.
AB  - Colorectal cancer is the second leading cause of cancer-related deaths in the
      U.S. Met, the receptor for hepatocyte growth factor (HGF), is over-expressed in
      colon tumors and is associated with poor prognosis. Recently, the green tea
      polyphenol (-)-epigallocatechin gallate (EGCG) was reported to suppress Met
      activation in breast cancer cells. However, the possible confounding effect of
      hydrogen peroxide (H(2)O(2)), produced when EGCG is added to cell culture media,
      was not assessed. In the present study, the human colon cancer cell lines HCT116
      and HT29 were used to examine the relationships between Met activation, EGCG
      treatment, and H(2)O(2) generation. At concentrations of 0.5, 1, and 5 microM,
      EGCG suppressed markedly the activation of Met in the presence of HGF.
      Concentrations of 10muM EGCG and below generated low amounts of H(2)O(2) (<1.5
      microM), whereas higher H(2)O(2) concentrations (>5 microM) were required to
      directly increase the phosphorylation of Met. Moreover, suppression of Met
      activation by EGCG occurred in the presence or absence of catalase, suggesting
      that such effects were not an 'artifact' of H(2)O(2) generated from EGCG in cell
      culture media. We conclude that EGCG might be a beneficial therapeutic agent in
      the colon, inhibiting Met signaling and helping to attenuate tumor
      spread/metastasis, independent of H(2)O(2)-related mechanisms.

PMID- 19744468
TI  - Synergistic anti-inflammatory effects of low doses of curcumin in combination
      with polyunsaturated fatty acids: docosahexaenoic acid or eicosapentaenoic acid.
AB  - Inflammatory response plays an important role not only in the normal physiology
      but also in the pathology such as cancers. As chronic inflammations are
      associated with malignancies, it is important to prevent inflammation-mediated
      neoplastic formation, promotion and/or progression. One possible intervention
      will be using cancer chemopreventive agents such as curcumin (CUR), a potent anti
      inflammatory and anti-oxidative stress compound. Polyunsaturated fatty acids
      (PUFA) such as docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA) are
      potent anti-inflammatory agents by decreasing the production of inflammatory
      eicosanoids, cytokines, and reactive oxygen species (ROS). The present study aims
      at examining whether CUR with DHA or EPA would have synergistic anti-inflammatory
      effects in RAW 264.7 cells. Non-toxic concentrations of single and combination of
      the compounds were investigated at 6, 12 and 24h. The nitric oxide (NO)
      suppression effects were most prominent at 24h. All the combinations of CUR and
      DHA or EPA with lower concentrations of CUR 5 microM and 25 microM of DHA or EPA
      were found to have synergistic effects in suppressing LPS-stimulated NO and
      endogenous NO levels. Importantly, very low doses of CUR 2.5 microM and DHA or
      EPA of 0.78 microM could synergistically suppress the LPS-induced prostaglandin
      E(2) (PGE(2)). The combinations were also found to suppress iNOS, COX-2, 5
      lipoxygenase (5-LOX) and cPLA(2) but induce HO-1. Taken together, the present
      study clearly shows the synergistic anti-inflammatory as well as anti-oxidative
      stress effects of CUR and PUFA.

PMID- 19744469
TI  - Mechanism of action of novel naphthofuranquinones on rat liver microsomal
      peroxidation.
AB  - In order to elucidate the effect on mammal systems of new derivatives from 2
      hydroxy-3-allyl-naphthoquinone, alpha-iodinated naphthofuranquinone (NPPN-3223),
      beta-iodinated naphthofuranquinone (NPPN-3222) and beta-methyl
      naphthofuranquinone (NPPN-3226) synthesized as possible trypanocidal agents,
      their effect on rat liver microsomal lipid peroxidation was investigated. They
      (a) inhibited NADPH-dependent, iron-catalyzed microsomal rat liver lipid
      peroxidation; (b) did not inhibit the tert-butyl hydroperoxide-dependent lipid
      peroxidation; (c) did not inhibit ascorbate-lipid peroxidation with the exception
      of NPPN-3226 which did inhibit it; (d) stimulated NADPH oxidation and microsomal
      oxygen uptake; (e) increased superoxide anion formation by NADPH-supplemented
      microsomes and (f) stimulated ascorbate oxidation. The three drugs were reduced
      to their seminaphthofuranquinone radical by the liver NADPH-P450 reductase
      system, as detected by ESR measurements. These results support the hypothesis
      that naphthofuranquinones reduction by microsomal NADPH-P450 reductase and
      semiquinone oxidation by molecular oxygen diverts electrons, preventing
      microsomal lipid peroxidation. In addition, hydroquinones and/or semiquinones
      formed by naphthofuranquinones reduction would be capable of lipid peroxidation
      inhibition and on interacting with the lipid peroxide radicals can lead to an
      antioxidant effect as we suggested for NPPN-3226 in close agreement to the
      inhibition of ascorbate-lipid peroxidation. Due to the properties of these
      molecules and their incoming structure developments, naphthofuranquinones would
      be considered as potentially promising therapeutic agents, mainly against Chagas
      disease.

PMID- 19744470
TI  - Cytotoxic, cytoprotective and antioxidant activities of resveratrol and analogues
      in C6 astroglioma cells in vitro.
AB  - Resveratrol (3,4',5-trans-trihydroxystilbene) and other hydroxystilbenes exhibit
      in vitro antioxidant as well as prooxidant effects. The antioxidant properties
      are assumed to enable these compounds to protect cells from oxidative damage. The
      prooxidant effects are held likely to be responsible for their cytotoxic, anti
      proliferative or pro-apoptotic effects observed in vitro. Regarding
      antioxidant/prooxidant activities in the past various studies were performed
      aiming at defining structure-activity relationships for hydroxystilbenes using
      cell-free systems. In the present study cultured C6 glioma cells were used in
      order to investigate the relationship between the antioxidant, cytoprotective and
      cytotoxic activities of resveratrol and selected analogues, e.g., 3,3',4',5-trans
      tetrahydroxystilbene (piceatannol), 3,3',5,5'-trans-tetrahydroxystilbene
      (3,3',5,5'-THS) and 3,3',4',5,5'-trans-pentahydroxystilbene (3,3',4',5,5'-PHS).
      All these compounds were cytotoxic to growth-arrested C6 cells, with EC50-values
      between 20 and 85 microM. A higher cytotoxic potency in proliferating cells
      indicated a specific cytostatic activity of resveratrol and 3,3',4',5,5'-PHS. All
      hydroxystilbenes studied inhibited cellular radical generation induced by cumene
      hydroperoxide (CHP). The rank order of antioxidant potency was
      resveratrol>piceatannol>3,3',5,5'-THS>3,3',4',5,5'-PHS. However, only resveratrol
      and piceatannol inhibited cellular radical generation at lower than cytotoxic
      concentrations. At subcytotoxic concentrations only piceatannol was able to
      protect the cells from damage caused by CHP. Taken together, these results show
      that neither the cytotoxic or cytostatic activities of hydroxystilbenes nor their
      cytoprotective and antioxidant activities in living cells can be predicted from
      their antioxidant and prooxidant activity, respectively, in cell-free systems.

PMID- 19744471
TI  - The acyl glucuronide metabolite of mycophenolic acid induces tubulin
      polymerization in vitro.
AB  - OBJECTIVES: The acyl glucuronide (AcMPAG) of mycophenolic acid (MPA) forms
      covalent protein adducts and possesses antiproliferative properties independent
      of IMPDH inhibition. The underlying mechanism is unknown. Disorganized tubulin
      polymerization prevents cell cycle progression. We investigated whether AcMPAG
      interacts with tubulin polymerization. DESIGN AND METHODS: AcMPAG (1.0-100
      microM) was incubated with bovine tubulin in the presence of GTP. Polymerization
      was followed at 340 nm. The time until onset and the extent of polymerization
      were determined. MPA (100 microM), phenolic glucuronide MPAG (100 microM), and
      paclitaxel (10 microM) served as controls. RESULTS: MPAG was without effect. The
      AcMPAG effect on tubulin polymerization was dose dependent and significantly
      stronger (about 2.5-fold) than that of MPA (n=4; p<0.05), but weaker than
      paclitaxel. CONCLUSIONS: MPA and AcMPAG can induce tubulin polymerization in the
      presence of GTP with AcMPAG being significantly stronger. This property of AcMPAG
      may contribute to its IMPDH independent antiproliferative effect.

PMID- 19744472
TI  - An IgG complexed form of vitamin B12 is a common cause of elevated serum
      concentrations.
AB  - OBJECTIVES: To report detailed investigations in a case of elevated serum B(12)
      due to the presence of an IgG-B(12) complex, to determine the prevalence of this
      phenomenon and to review the literature. DESIGN AND METHODS: 431 samples with
      elevated B(12) (median 1250 ng/L, range 901-114,480 ng/L) were treated with
      polyethylene glycol to precipitate immunoglobulin complexes. Samples with >50% of
      precipitable B(12) (PPB(12)) were further investigated by protein G adsorption,
      gel filtration chromatography and measurement of B(12) on different analytical
      platforms. RESULTS: Median PPB(12) was 22.6%, but in 35 samples (8.1%), median
      PPB(12) was more than 50%. Investigation of 27 of these samples with protein G
      Sepharose confirmed the presence of an IgG-B(12) complex in 24, and in 15 cases,
      B(12) fell to within the reference range. After treatment of serum with reagents
      releasing B(12) from binding proteins, immunoreactivity co-eluted with free
      B(12). Immunoreactivity of the IgG-bound form of B(12) was confirmed using five
      B(12) assays in common use in the UK. CONCLUSIONS: At least 8% of samples with
      elevated vitamin B(12) contain an immunoglobulin complexed form of circulating
      B(12); this possibility should be considered in the interpretation of results.

PMID- 19744474
TI  - Pharmacological effects of carvedilol on T-type calcium current in murine HL-1
      cells.
AB  - Carvedilol is widely used in the treatment of cardiovascular diseases including
      atrial fibrillation. T-type Ca(2+) channels have been recognized recently in the
      mechanisms underlying atrial arrhythmias. However, it is unclear whether
      carvedilol may affect the T-type Ca(2+) channel. The present study evaluated the
      pharmacological effects of carvedilol on T-type calcium current (I(Ca,T)) in the
      murine HL-1 cell line. I(Ca)(,T) was recorded by the whole-cell patch-clamp
      technique. Calcium transient was monitored by the fluorescent dye Fluo-4/AM and
      confocal laser scanning microscopy. Carvedilol reversibly inhibited I(Ca)(,T) in
      a concentration-dependent manner, with an IC50 of 2.1 microM. 3 microM carvedilol
      was found to decrease the peak I(Ca)(,T) amplitude at -20 mV from 20.1+/-1.8pA/pF
      to 10.9+/-2.1pA/pF. Carvedilol significantly shifted the steady-state
      inactivation curve of I(Ca)(,T) towards more negative potential by 12.8 mV, while
      the activation curve was not significantly altered. Carvedilol delayed recovery
      from inactivation of I(Ca)(,T), time constant (tau) was 112.4+/-3.5 ms in control
      and 270.1+/-4.7 ms in carvedilol. Carvedilol-induced inhibition rate in I(Ca)(,T)
      was enhanced with the increase in stimuli frequency, the inhibitory rate was
      23.2+/-4.1% at 0.2 Hz and 47.2+/-0.6% at 2 Hz. Carvedilol still produced the
      significant decrease in the amplitude of I(Ca)(,T) in the presence of H-89, PKA
      inhibitor. Carvedilol significantly inhibited the amplitude of the calcium
      transient in a concentration-dependent manner. These findings indicate that
      carvedilol inhibits I(Ca)(,T) in atrial cells by mechanisms involving
      preferential interaction with the inactivated state of T-type Ca(2+) channel.

PMID- 19744473
TI  - Retinoblastoma family protein promotes normal R8-photoreceptor differentiation in
      the absence of rhinoceros by inhibiting dE2F1 activity.
AB  - The retinoblastoma gene Rb is a prototype tumor suppressor which is conserved in
      Drosophila. Although much is known about the roles of Rb in cell proliferation
      and apoptosis, much less is known about how Rb regulates cell differentiation.
      Inactivation of Drosophila Rb (rbf) exhibited subtle differentiation defects
      similar to inactivation of Rb in mice, suggesting the existence of redundant
      mechanisms in the control of cell differentiation. To test this possibility and
      to characterize the role of Rbf in cell differentiation during retinal
      development, we carried out a genetic screen and identified a mutation in
      rhinoceros (rno), which leads to synergistic differentiation defects in
      conjunction with rbf inactivation. Characterization of an early differentiation
      defect, the multiple-R8 phenotype, revealed that this phenotype was caused by
      limiting amounts of Notch signaling due to reduced expression of the Notch
      ligand, Delta (Dl). Decreasing the gene dosage of Dl enhanced the multiple-R8
      phenotype, while increasing the level of Dl suppressed this phenotype.
      Interestingly, removal of the transcriptional activation of dE2F1 partially
      restores Dl expression in rbf,rno mutant clones and suppresses the associated
      differentiation defects, indicating that this differentiation function of RBF is
      mediated by its regulation of dE2F1 activity.

PMID- 19744475
TI  - Modulatory effects of probenecid on the nitroglycerin-induced changes in the rat
      caudal trigeminal nucleus.
AB  - Four hours after systemic administration of the nitric oxide donor nitroglycerin
      (10 mg/kg bodyweight, s.c.), the neurons of the rat caudal trigeminal nucleus are
      activated, the area covered by calcitonin gene-related peptide (CGRP)
      immunoreactive fibres is decreased and the neuronal nitric oxide synthase (nNOS)-
      and the calmodulin-dependent protein kinase II alpha (CamKIIalpha)-immunopositive
      neurons in the same area are increased. Probenecid is a non-selective inhibitor
      of multidrug-resistance associated proteins and organic anion transporters thus
      it can modulate the transport functions in the central nervous system influencing
      nociception. Accordingly, the aim of the present experiments was to examine the
      effects of probenecid administration on the nitroglycerin-induced expressions of
      nNOS, CamKIIalpha and CGRP in the rat caudal trigeminal nucleus. Probenecid (200
      mg/kg bodyweight, i.p.) pretreatment proved to mitigate the nitroglycerin-induced
      changes in expression in the rat caudal trigeminal nucleus. The data suggest that
      the changes caused by nitroglycerin in the expressions of CGRP, nNOS and
      CamKIIalpha can be influenced by probenecid modulating the inflammatory functions
      in the nervous system. These data may be of relevance for the pathogenesis of
      migraine headache.

PMID- 19744476
TI  - Flavonoid quercetin protects against swimming stress-induced changes in oxidative
      biomarkers in the hypothalamus of rats.
AB  - Quercetin is a bioflavonoid abundant in onions, apples, tea and red wine and one
      of the most studied flavonoids. Dietary quercetin intake is suggested to be
      health promoting, but this assumption is mainly based on mechanistic studies
      performed in vitro. The objective of this study was to investigate the effect of
      quercetin on stress-induced changes in oxidative biomarkers in the hypothalamus
      of rats. Adult male Sprague Dawley rats were subjected to forced swimming stress
      for 45 min daily for 14 days. Effect of quercetin at three different doses (10,
      20 and 30 mg/kg body weight) on serum corticosterone and oxidative biomarkers
      (lipid hydroperoxides, antioxidant enzymes and total antioxidants) was estimated.
      Swimming stress significantly increased the serum corticosterone and lipid
      hydroperoxide levels. A significant decrease in total antioxidant levels and
      super oxide dismutase, glutathione peroxidase and catalase levels was seen in the
      hypothalamus after stress and treatment with quercetin significantly increased
      these oxidative parameters and there was a significant decrease in lipid
      hydroperoxide levels. These data demonstrate that forced swimming stress produced
      a severe oxidative damage in the hypothalamus and treatment with quercetin
      markedly attenuated these stress-induced changes. Antioxidant action of quercetin
      may be beneficial for the prevention and treatment of stress-induced oxidative
      damage in the brain.

PMID- 19744477
TI  - Emodin induces a reactive oxygen species-dependent and ATM-p53-Bax mediated
      cytotoxicity in lung cancer cells.
AB  - Emodin (1,3,8-trihydroxy-6-methyl-anthraquinone), a natural anthraquinone
      compound isolated from the rhizome of rhubarb, has been reported to suppress
      tumor growth in many clinical situations. Here, we demonstrate that emodin
      induces apoptosis in human lung adenocarcinoma A549 cells by activating a
      reactive oxygen species-elicited ATM-p53-Bax signaling pathway. In response to
      emodin treatment, p53 protein increases in A549 cells, which in turn up-regulates
      Bax expression. Co-treating cells with either a p53 inhibitor or respectively
      knocking down the expression of p53 and Bax by shRNA extensively diminished
      emodin-induced cell viability, caspase 3 activation and the release of cytochrome
      c from the mitochondria, indicating the crucial role for p53/Bax in emodin
      mediated cytotoxicity. Pre-treating cells with the antioxidant ascorbic acid not
      only prohibited the induction of reactive oxygen species by emodin, but also
      inhibited the up-regulation of p53. Upon emodin treatment, p53 is phosphorylated
      at Ser(15), which is accompanied by the ATM phosphorylation at Ser(1981). Both of
      these events could also be blocked by the presence of ascorbic acid. Moreover,
      knockdown of ATM by siRNA significantly reduced p53 phosphorylation and
      stabilization, indicating the upstream role of emodin-induced reactive oxygen
      species generation in ATM activation and following p53 phosphorylation and
      stabilization. Taken together, our results demonstrate that emodin-induced
      reactive oxygen species generation activates an ATM-p53-Bax-dependent signaling
      pathway, which consequently leads to mitochondria-dependent apoptotic cell death
      in human lung adenocarcinoma A549 cells.

PMID- 19744478
TI  - Molecular biomarkers for autoimmune retinopathies: significance of anti
      transducin-alpha autoantibodies.
AB  - Autoimmune retinopathies (AR) are uncommon retinal degenerations with vision loss
      associated with unique clinical symptoms and findings and with serum anti-retinal
      autoantibodies. The experimental and clinical studies corroborate that
      autoantibodies in high titers can penetrate into the retina affecting function of
      the target antigens, which leads to retinal dysfunction and degeneration. Anti
      recoverin and anti-enolase alpha-enolase autoantibodies were more frequently
      recognized in AR but autoantibodies with other specificities have also been
      documented, indicating immunological heterogeneity. Our goal was to examine the
      associations of anti-retinal autoantibodies with retinopathy in order to identify
      molecular biomarkers for better diagnosis and prognosis of retinopathies. In
      these studies we examined 39 patients (10 with cancers) of average age of
      approximately 57 years old with sudden onset of unexplained progressive vision
      loss and the presence of circulating serum autoantibodies against 40-kDa retinal
      protein. The patients presented the retinal phenotype characterized by defects in
      visual fields and reduced scotopic ERG responses. Anti-40-kDa autoantibodies had
      specificity to the amino terminus of transducin-alpha. None of the normal
      subjects' sera had anti-40-kDa autoantibodies. In conclusion, the clinical
      phenotype of patients with anti-transducin-alpha autoantibodies differed from
      other phenotypes of AR. These patients, often women at a ratio approximately 2:1,
      had defects in rod (scotopic) photoreceptor function and typically did not have
      cancers, whereas the anti-recoverin phenotype is associated with cancer and
      severe loss of rod and cones function, and anti-enolase retinopathy typically
      presents with cone dysfunction and is equal in cancer and non-cancer patients.
      Our studies suggest that anti-transducin autoantibodies can serve as molecular
      biomarkers for retinal phenotypes and could be used for progression of retinal
      dysfunction and degeneration.

PMID- 19744479
TI  - Shiga toxin 1 interaction with enterocytes causes apical protein mistargeting
      through the depletion of intracellular galectin-3.
AB  - Shiga toxins (Stx) 1 and 2 are responsible for intestinal and systemic sequelae
      of infection by enterohemorrhagic Escherichia coli (EHEC). However, the
      mechanisms through which enterocytes are damaged remain unclear. While secondary
      damage from ischemia and inflammation are postulated mechanisms for all
      intestinal effects, little evidence excludes roles for more primary toxin effects
      on intestinal epithelial cells. We now document direct pathologic effects of Stx
      on intestinal epithelial cells. We study a well-characterized rabbit model of
      EHEC infection, intestinal tissue and stool samples from EHEC-infected patients,
      and T84 intestinal epithelial cells treated with Stx1. Toxin uptake by intestinal
      epithelial cells in vitro and in vivo causes galectin-3 depletion from
      enterocytes by increasing the apical galectin-3 secretion. This Shiga toxin
      mediated galectin-3 depletion impairs trafficking of several brush border
      structural proteins and transporters, including villin, dipeptidyl peptidase IV,
      and the sodium-proton exchanger 2, a major colonic sodium absorptive protein. The
      mistargeting of proteins responsible for the absorptive function might be a key
      event in Stx1-induced diarrhea. These observations provide new evidence that
      human enterocytes are directly damaged by Stx1. Conceivably, depletion of
      galectin-3 from enterocytes and subsequent apical protein mistargeting might even
      provide a means whereby other pathogens might alter intestinal epithelial
      absorption and produce diarrhea.

PMID- 19744480
TI  - Regulation of MYPT1 stability by the E3 ubiquitin ligase SIAH2.
AB  - Myosin phosphatase target subunit 1 (MYPT1), together with catalytic subunit of
      type1 delta isoform (PP1cdelta) and a small 20-kDa regulatory unit (M20), form a
      heterotrimeric holoenzyme, myosin phosphatase (MP), which is responsible for
      regulating the extent of myosin light chain phosphorylation. Here we report the
      identification and characterization of a molecular interaction between Seven in
      absentia homolog 2 (SIAH2) and MYPT1 that resulted in the proteasomal degradation
      of the latter in mammalian cells, including neurons and glia. The interaction
      involved the substrate binding domain of SIAH2 (aa 116-324) and a central region
      of MYPT1 (aa 445-632) containing a degenerate consensus Siah-binding motif
      RLAYVAP (aa 493-499) evolutionally conserved from fish to humans. These findings
      suggest a novel mechanism whereby the ability of MP to modulate myosin light
      chain might be regulated by the degradation of its targeting subunit MYPT1
      through the SIAH2-ubiquitin-proteasomal pathway. In this manner, the turnover of
      MYPT1 would serve to limit the duration and/or magnitude of MP activity required
      to achieve a desired physiological effect.

PMID- 19744481
TI  - Oligomers of beta-amyloid are sequestered into and seed new plaques in the brains
      of an AD mouse model.
AB  - Amyloid plaque deposition in the brain is a hallmark of Alzheimer's disease, but
      recent evidence indicates that the disease may be primarily caused by soluble
      amyloid-beta (1-42) (Abeta) oligomers or Abeta-derived diffusible ligands
      (ADDLs). ADDLs induce cognitive deficits in animal models and are thought to
      assemble in vitro by a mechanism apart from plaque formation. To investigate the
      in vivo relationship of ADDLs and plaques, biotin-labeled ADDLs (bADDLs) or
      amylin oligomers (bAMs) were injected into the hippocampus of hAPP overexpressing
      mice. The brains were collected 1 or 5 weeks after the last treatment and were
      processed for immunohistochemistry. Staining of tissue 1 week post-treatment
      showed bADDLs had diffused throughout the tissue and incorporated into plaques.
      Additionally, small deposits of thioflavin S-negative bADDLs were observed. At 5
      weeks post-treatment, thioflavin S-positive material continued to accumulate
      around plaques containing bADDLs. Thioflavin S-positive material also accrued
      around bADDL deposits, implying that bADDLs were capable of seeding new plaques.
      In contrast, bAMs cleared from the brain and did not accumulate in plaques.
      Together, these data indicate that ADDLs are able to contribute to in vivo plaque
      formation in a peptide-specific manner.

PMID- 19744482
TI  - Tau-directed drug discovery for Alzheimer's disease and related tauopathies: a
      focus on tau assembly inhibitors.
AB  - The microtubule-associated protein tau forms insoluble filaments that deposit as
      neurofibrillary tangles (NFTs) in the brains of those with Alzheimer's disease
      (AD) and other related neurodegenerative disorders. The presence of both NFTs and
      amyloid beta (Abeta)-containing senile plaques within the brain is required to
      confirm the diagnosis of AD. However, the demonstration that familial AD can be
      caused by mutations that result in increased Abeta production has resulted in AD
      drug discovery strategies that are largely focused on reducing brain Abeta
      levels, with substantially less emphasis on tau-directed approaches. This trend
      may be changing, as there are an increasing number of research programs that are
      exploring ways to reduce NFTs in AD and related tauopathies. We briefly review
      recent advances in tau-based drug discovery, with an emphasis on the
      identification of compounds that inhibit the assembly of tau into multimers and
      fibrils.

PMID- 19744483
TI  - Amyloid-beta fibrillogenesis: structural insight and therapeutic intervention.
AB  - Structural insight into the conformational changes associated with aggregation
      and assembly of fibrils has provided a number of targets for therapeutic
      intervention. Solid-state NMR, hydrogen/deuterium exchange and mutagenesis
      strategies have been used to probe the secondary and tertiary structure of
      amyloid fibrils and key intermediates. Rational design of peptide inhibitors
      directed against key residues important for aggregation and stabilization of
      fibrils has demonstrated effectiveness at inhibiting fibrillogenesis. Studies on
      the interaction between Abeta and cell membranes led to the discovery that
      inositol, the head group of phosphatidylinositol, inhibits fibrillogenesis. As a
      result, scyllo-inositol is currently in clinical trials for the treatment of AD.
      Additional small-molecule inhibitors, including polyphenolic compounds such as
      curcumin, (-)-epigallocatechin gallate (EGCG), and grape seed extract have been
      shown to attenuate Abeta aggregation through distinct mechanisms, and have shown
      effectiveness at reducing amyloid levels when administered to transgenic mouse
      models of AD. Although the results of ongoing clinical trials remain to be seen,
      these compounds represent the first generation of amyloid-based therapeutics,
      with the potential to alter the progression of AD and, when used
      prophylactically, alleviate the deposition of Abeta.

PMID- 19744484
TI  - What can man do without basal ganglia motor output? The effect of combined
      unilateral subthalamotomy and pallidotomy in a patient with Parkinson's disease.
AB  - We have studied motor performance in a man with Parkinson's disease (PD) in whom
      thermolytic lesions of the left subthalamic and left globus pallidus nuclei
      interrupted the basal ganglia (BG)-thalamo-cortical motor circuit in the left
      hemisphere. This allowed us to study remaining motor capabilities in the absence
      of aberrant BG activity typical of PD. Movements of the left arm were slow and
      parkinsonian whereas movement speed and simple reaction times (RT) of the right
      (operated) arm were within the normal range with no obvious deficits in a range
      of daily life activities. Two main abnormalities were found with the right hand.
      (a) Implicit sequence learning in a probabilistic serial reaction time task was
      absent. (b) In a go/no-go task when the percent of no-go trials increased, the RT
      superiority with the right hand was lost. These deficits are best explained by a
      failure of the cortex, deprived of BG input, to facilitate responses in a
      probabilistic context. Our findings confirm the idea that it is better to stop BG
      activity than allowing faulty activity to disrupt the motor system but dispute
      earlier claims that interrupting BG output in PD goes without an apparent
      deficit. From a practical viewpoint, our observations indicate that the risk of
      persistent dyskinesias need not be viewed as a contraindication to subthalamotomy
      in PD patients since they can be eliminated if necessary by a subsequent
      pallidotomy without producing deficits that impair activities of daily life.

PMID- 19744485
TI  - Limit of detection of sedimentation and counting technique (SCT) for Echinococcus
      multilocularis diagnosis, estimated under experimental conditions.
AB  - The aim of this study was to estimate the limit of detection of sedimentation and
      counting techniques (SCT) in Echinococcus multilocularis diagnosis. Samples of
      small intestines, experimentally enriched with known numbers of E. multilocularis
      tapeworms, were used. Forty intestinal samples containing 2, 5, 10, and 30 E.
      multilocularis tapeworms (10 samples for each level) were prepared and examined
      according to SCT. E. multilocularis was detected in 30%, 40%, 60%, and 100% in
      samples enriched with 2, 5, 10, and 30 tapeworms, respectively. The limit of
      detection was estimated at 10 E. multilocularis tapeworms per sample of intestine
      (for 60% probability of obtaining positive results). There was a wide dispersion
      of counting results; these were observed in samples containing the same numbers
      of tapeworms, which indicates the low repeatability of the method. The
      limitations of SCT determined in this experiment should be considered when
      analysing the prevalence of E. multilocularis in carnivores.

PMID- 19744486
TI  - Distinct kinetics of (H/K/N)Ras glucosylation and Rac1 glucosylation catalysed by
      Clostridium sordellii lethal toxin.
AB  - Mono-glucosylation of (H/K/N)Ras by Clostridium sordellii lethal toxin (TcsL)
      blocks critical survival signaling pathways, resulting in apoptotic cell death.
      One yet unsolved problem in studies on TcsL is the lack of a method allowing the
      specific detection of (H/K/N)Ras glucosylation. In this study, we identify the
      Ras(Mab 27H5) antibody as a glucosylation-sensitive antibody capable for the
      immunoblot detection of (H/K/N)Ras glucosylation in TcsL-treated cells.
      Alternative Ras antibodies including the K-Ras(Mab F234) antibody or the v-H
      Ras(Mab Y13-159) antibody recognize Ras proteins regardless of glucosylation.
      (H/K)Ras are further shown to be more efficaciously glucosylated by TcsL than
      Rac1 in rat basophilic leukemia cells as well as in a cell-free system.

PMID- 19744487
TI  - A single-step procedure of recombinant library construction for the selection of
      efficiently produced llama VH binders directed against cancer markers.
AB  - Heavy chain antibodies are naturally occurring in camelidae (camels and llamas).
      Their variable domain (VHH) can be efficiently produced as a recombinant protein
      in E. coli with a large range of applications in the fields of diagnostics and
      immunotherapy. Standard cloning approach involves resolution of VHH from the
      heavy chain variable domain of conventional antibodies (VH) by a nested PCR
      amplification followed by a phage display based selection. Present work
      illustrates that in contrast to usual finding, specific, good affinity and
      efficiently expressed VH domain of conventional antibodies can be selected from
      the co-amplification products of VH and VHH cDNAs. Sequence analysis illustrated
      that following the two first rounds of selection against cancer markers, similar
      number of VH and VHH binders were observed. However, after a third round, the
      more specific binders directed against p53, VEGF, BCL-2 proteins surprisingly
      contain only VH specific hallmarks. Characterisation of the specificity, affinity
      and productivity of selected VH binders is described. Because llama VHs show
      higher sequence and structural homology with the human VH III group than llama
      VHHs (Vu et al., 1997), they constitute very interesting agents in therapeutic
      applications, especially in human immunotherapy and cancer treatment.

PMID- 19744488
TI  - Specificities of atrial electrophysiology: Clues to a better understanding of
      cardiac function and the mechanisms of arrhythmias.
AB  - The electrical properties of the atria and ventricles differ in several aspects
      reflecting the distinct role of the atria in cardiac physiology. The study of
      atrial electrophysiology had greatly contributed to the understanding of the
      mechanisms of atrial fibrillation (AF). Only the atrial L-type calcium current is
      regulated by serotonine or, under basal condition, by phosphodiesterases. These
      distinct regulations can contribute to I(Ca) down-regulation observed during AF,
      which is an important determinant of action potential refractory period
      shortening. The voltage-gated potassium current, I(Kur), has a prominent role in
      the repolarization of the atrial but not ventricular AP. In many species, this
      current is based on the functional expression of K(V)1.5 channels, which might
      represent a specific therapeutic target for AF. Mechanisms regulating the
      trafficking of K(V)1.5 channels to the plasma membrane are being actively
      investigated. The resting potential of atrial myocytes is maintained by various
      inward rectifier currents which differ with ventricle currents by a reduced
      density of I(K1), the presence of a constitutively active I(KACh) and distinct
      regulation of I(KATP). Stretch-sensitive or mechanosensitive ion channels are
      particularly active in atrial myocytes and are involved in the secretion of the
      natriuretic peptide. Integration of knowledge on electrical properties of atrial
      myocytes in comprehensive schemas is now necessary for a better understanding of
      the physiology of atria and the mechanisms of AF.

PMID- 19744490
TI  - Intracellular Ca(2+)- and PKC-dependent upregulation of T-type Ca(2+) channels in
      LPC-stimulated cardiomyocytes.
AB  - Lysophosphatidylcholine (LPC) accumulation in intracellular and/or interstitial
      space in cardiomyocytes may underlie as a mechanism for tachycardia and various
      arrhythmias during cardiac ischemia, which is usually accompanied by elevation of
      intracellular Ca(2+) concentration ([Ca(2+)](i)). The present study was therefore
      designed to investigate possible mechanisms responsible for [Ca(2+)](i) elevation
      by LPC focusing on T-type Ca(2+) channel current (I(Ca.T)). LPC as well as
      phorbol 12-myristate 13-acetate (PMA) significantly accelerated the beating rates
      of neonatal rat cardiomyocytes. Augmentation of I(Ca.T) by LPC was dependent on
      the intracellular Ca(2+) concentration: an increase of I(Ca.T) was significantly
      larger in high [Ca(2+)](i) condition (pCa=7) than those in low [Ca(2+)](i)
      condition (pCa=11). In heterologous expression system by use of human cardiac
      Ca(V)3.1 and Ca(V)3.2 channels expressed in HEK293 cells, LPC augmented Ca(V)3.2
      channel current (I(Cav3.2)) in a concentration-dependent manner but not Ca(V)3.1
      channel current (I(Cav3.1)). Augmentation of I(Cav3.2) by LPC was highly
      [Ca(2+)](i) dependent: I(Cav3.2) was unchanged when pCa was 11 but was markedly
      increased when [Ca(2+)](i) was higher than 10(-10) M (pCa<or=10) by LPC
      application (10-50 microM). A specific inhibitor of protein kinase Calpha (Ro-32
      0432) attenuated the increase of I(Cav3.2) by LPC. LPC stimulates I(Ca.T) in a
      [Ca(2+)](i)-dependent manner via PKCalpha activation, which may play a role in
      triggering arrhythmias in pathophysiological conditions of the heart.

PMID- 19744489
TI  - Interaction of myocardial insulin receptor and IGF receptor signaling in exercise
      induced cardiac hypertrophy.
AB  - Insulin-like growth factor-1 (IGF-1) signaling has recently been implicated in
      the development of cardiac hypertrophy after long-term endurance training, via
      mechanisms that may involve energetic stress. Given the potential overlap of
      insulin and IGF-1 signaling we sought to determine if both signaling pathways
      could contribute to exercise-induced cardiac hypertrophy following shorter-term
      exercise training. Studies were performed in mice with cardiac-specific IGF-1
      receptor (IGF1R) knockout (CIGFRKO), mice with cardiac-specific insulin receptor
      (IR) knockout (CIRKO), CIGFRKO mice that lacked one IR allele in cardiomyocytes
      (IGFR-/-IR+/-), and CIRKO mice that lacked one IGF1R allele in cardiomyocytes
      (IGFR+/-IR-/-). Intravenous administration of IGF-1 or 75 hours of swimming over
      4 weeks increased IGF1R tyrosine phosphorylation in the heart in control and
      CIRKO mice but not in CIGFRKO mice. Intriguingly, IR tyrosine phosphorylation in
      the heart was also increased following IGF-1 administration or exercise training
      in control and CIGFRKO mice but not in CIRKO mice. The extent of cardiac
      hypertrophy following exercise training in CIGFRKO and CIRKO mice was comparable
      to that in control mice. In contrast, exercise-induced cardiac hypertrophy was
      significantly attenuated in IGFR-/-IR+/- and IGFR+/-IR-/- mice. Thus, IGF-1 and
      exercise activates both IGF1R and IR in the heart, and IGF1R- and IR-mediated
      signals may serve redundant roles in the hypertrophic responses of the heart to
      exercise training.

PMID- 19744491
TI  - Molecular and functional remodeling of I(to) by angiotensin II in the mouse left
      ventricle.
AB  - The transient outward potassium current (I(to)) in cardiac myocytes is mainly
      mediated by members of the Kv4 subfamily of voltage-gated potassium channels.
      Several in vitro studies have shown that angiotensin II (Ang II), which plays an
      important role in the development of cardiac hypertrophy, rapidly downregulates
      Kv4.3 mRNA expression. However, it is not clear whether Ang II regulates I(to)in
      vivo and whether this regulation may depend on alterations in Kv4.3 gene
      expression. To address this question, we determined the effects of acute (24 h)
      and chronic (14 days) exogenous infusions of Ang II on I(to) and the expression
      of its channel subunits in the mouse left ventricle. Ang II rapidly increased
      blood pressure and reduced Kv4.2 but not Kv4.3 mRNA levels in the absence of
      cardiac hypertrophy. In response to chronically elevated Ang II levels cardiac
      hypertrophy developed, which was associated with a downregulation of Kv4.2 and
      Kv4.3 mRNA levels, and an upregulation of Kv1.4 mRNA levels. In contrast, neither
      KChIP2 mRNA levels nor amplitude or macroscopic inactivation kinetics of I(to)
      were affected by the acute or chronic Ang II treatments. Consistent with the
      unchanged I(to) amplitude, Kv4.2, Kv4.3, and KChIP protein expression levels were
      similar after chronic Ang II and sham treatment. Our findings demonstrate that
      elevations of Ang II concentrations that induce hypertension and cardiac
      hypertrophy do not alter the amplitude of I(to) in the mouse left ventricle.
      Furthermore, they suggest that functional expression of cardiac I(to) in mice is
      stabilized by KChIP2.

PMID- 19744492
TI  - Involvement of Src in L-type Ca2+ channel depression induced by macrophage
      migration inhibitory factor in atrial myocytes.
AB  - Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that
      controls inflammatory processes, and inflammation is known to play an important
      role in the pathogenesis of atrial fibrillation (AF). The present study sought to
      investigate whether MIF expression is responsible for the changes in L-type Ca2+
      currents (I(Ca,L)) seen in AF. Whole-cell voltage-clamp recordings and
      biochemical assays were used to study the regulation and expression of I(Ca,L) in
      human atrial myocytes and in HL-1 cells. Basal I(Ca,L) was reduced in AF compared
      to sinus rhythm (SR) controls, mRNA and protein levels of the pore-forming
      alpha1C subunit of L-type Ca2+ channel (LCC alpha1C) were also decreased, while
      MIF expression levels were increased in AF. Levels of Src and activated Src (p
      Src Y416) were higher in AF than in SR. Treatment of atrial myocytes from a
      patient with SR with human recombinant MIF (rMIF) (40 nM, 1 h) was found to
      depress I(Ca,L) amplitudes, while mouse rMIF (20 or 40 nM, 24 h) suppressed peak
      I(Ca,L) in HL-1 cells by approximately 69% and approximately 83% in a
      concentration-dependent manner. Mouse rMIF impaired the time-dependent recovery
      from inactivation of I(Ca,L) and down-regulated LCC alpha1C subunit levels. The
      depression of I(Ca,L) and decrease of LCC protein levels induced by rMIF were
      prevented by the Src inhibitors genistein and PP1. These results implicate MIF in
      the electrical remodeling that accompanies AF, probably by decreasing I(Ca,L)
      amplitudes through impairment of channel function, down-regulation of LCC alpha1C
      subunit levels, and the activation of c-Src kinases in atrial myocytes.

PMID- 19744493
TI  - Differential K(ATP) channel pharmacology in intact mouse heart.
AB  - Classically, cardiac sarcolemmal K(ATP) channels have been thought to be composed
      of Kir6.2 (KCNJ11) and SUR2A (ABCC9) subunits. However, the evidence is strong
      that SUR1 (sulfonylurea receptor type 1, ABCC8) subunits are also expressed in
      the heart and that they play a significant functional role in the atria. To
      examine this further, we have assessed the effects of isotype-specific potassium
      channel-opening drugs, diazoxide (specific to SUR1>SUR2A) and pinacidil
      (SUR2A>SUR1), in intact hearts from wild-type mice (WT, n=6), SUR1(-/-) (n=6),
      and Kir6.2(-/-) mice (n=5). Action potential durations (APDs) in both atria and
      ventricles were estimated by optical mapping of the posterior surface of
      Langendorff-perfused hearts. To confirm the atrial effect of both openers,
      isolated atrial preparations were mapped in both WT (n=4) and SUR1(-/-) (n=3)
      mice. The glass microelectrode technique was also used to validate optical action
      potentials. In WT hearts, diazoxide (300 microM) decreased APD in atria (from
      33.8+/-1.9 ms to 24.2+/-1.1 ms, p<0.001) but was without effect in ventricles
      (APD 60.0+/-7.6 ms vs. 60.8+/-7.5 ms, respectively, NS), consistent with an
      atrial-specific role for SUR1. The absence of SUR1 resulted in loss of efficacy
      of diazoxide in SUR1(-/-) atria (APD 36.8+/-1.9 ms vs. 36.8+/-2.8 ms,
      respectively, NS). In contrast, pinacidil (300 microM) significantly decreased
      ventricular APD in both WT and SUR1(-/-) hearts (from 60.0+/-7.6 ms to 29.8+/-3.5
      ms in WT, p<0.001, and from 63.5+/-2.1 ms to 24.8+/-3.8 ms in SUR1(-/-),
      p<0.001), but did not decrease atrial APD in either WT or SUR1(-/-) hearts.
      Glibenclamide (10 microM) reversed the effect of pinacidil in ventricles and
      restored APD to control values. The absence of Kir6.2 subunits in Kir6.2(-/-)
      hearts resulted in loss of efficacy of both openers (APD 47.2+/-2.2 ms vs. 47.6+/
      2.1 ms and 50.8+/-2.4 ms, and 90.6+/-5.7 ms vs. 93.2+/-6.5 ms and 117.3+/-6.4 ms,
      for atria and ventricle in control versus diazoxide and pinacidil, respectively).
      Collectively, these results indicate that in the same mouse heart, significant
      differential K(ATP) pharmacology in atria and ventricles, resulting from SUR1
      predominance in forming the atrial channel, leads to differential effects of
      potassium channel openers on APD in the two chambers.

PMID- 19744494
TI  - SERCA1 expression enhances the metabolic efficiency of improved contractility in
      post-ischemic heart.
AB  - Myocardial stunning is characterized by a metabolic uncoupling from function as
      mitochondrial tricarboxylic acid (TCA) cycle and oxygen consumption remain normal
      despite reduced contractility. Overexpression of the sarco-endoplasmic reticulum
      Ca2+-ATPase (SERCA1) in hearts has recently been reported to reduce dysfunction
      at reperfusion. In this study we determine whether the metabolic coupling to
      function improves with SERCA treatment. PBS (control) or adenovirus carrying the
      cDNA for SERCA1 was delivered via coronary perfusion in vivo to Sprague-Dawley
      rat hearts. Three days following gene transfer, isolated hearts were perfused
      with 0.4 mM [2,4,6,8,10,12,14,16-13C8] palmitate and 5 mM glucose, and subjected
      to 15-min ischemia followed by 40-min reperfusion. Consistent with myocardial
      stunning, rate pressure product (RPP) and left ventricular developed pressure
      (LVDP) were depressed 30-40% (p<0.05) in the PBS group. With SERCA1
      overexpression, dP/dt was 20% greater than controls (p<0.05), and LVDP and RPP
      recovered to pre-ischemic values. From dynamic 13C NMR, TCA cycle flux at
      reperfusion was similar to pre-ischemic values for both groups. Therefore, the
      efficiency of coupling between cardiac work and TCA cycle flux was restored with
      SERCA1 treatment. Oxidative efficiency was also enhanced with SERCA1 as cytosolic
      NADH transport into the mitochondria was significantly greater compared to the
      PBS group. In addition, the phosphocreatine to ATP ratio (PCr/ATP) was not
      compromised with SERCA1 expression, despite enhanced function, and depressed
      fatty acid oxidation at 40-min reperfusion in the PBS group was not reversed with
      SERCA1. These data demonstrate that metabolic coupling and NADH transport are
      significantly improved with SERCA1 treatment.

PMID- 19744495
TI  - Cardiac sodium channel Na(v)1.5 and interacting proteins: Physiology and
      pathophysiology.
AB  - The cardiac voltage-gated Na(+) channel Na(v)1.5 generates the cardiac Na(+)
      current (INa). Mutations in SCN5A, the gene encoding Na(v)1.5, have been linked
      to many cardiac phenotypes, including the congenital and acquired long QT
      syndrome, Brugada syndrome, conduction slowing, sick sinus syndrome, atrial
      fibrillation, and dilated cardiomyopathy. The mutations in SCN5A define a sub
      group of Na(v)1.5/SCN5A-related phenotypes among cardiac genetic channelopathies.
      Several research groups have proposed that Na(v)1.5 may be part of multi-protein
      complexes composed of Na(v)1.5-interacting proteins which regulate channel
      expression and function. The genes encoding these regulatory proteins have also
      been found to be mutated in patients with inherited forms of cardiac arrhythmias.
      The proteins that associate with Na(v)1.5 may be classified as (1)
      anchoring/adaptor proteins, (2) enzymes interacting with and modifying the
      channel, and (3) proteins modulating the biophysical properties of Na(v)1.5 upon
      binding. The aim of this article is to review these Na(v)1.5 partner proteins and
      to discuss how they may regulate the channel's biology and function. These recent
      investigations have revealed that the expression level, cellular localization,
      and activity of Na(v)1.5 are finely regulated by complex molecular and cellular
      mechanisms that we are only beginning to understand.

PMID- 19744496
TI  - I(Ks) restricts excessive beat-to-beat variability of repolarization during beta
      adrenergic receptor stimulation.
AB  - In vivo studies have suggested that increased beat-to-beat variability of
      ventricular repolarization duration (BVR) is a better predictor of drug-induced
      torsades de pointes than repolarization prolongation alone. Cellular BVR and its
      dynamics before proarrhythmic events are poorly understood. We investigated
      differential responses of BVR in single myocytes during I(Ks) blockade versus
      I(Kr) blockade and late-I(Na) augmentation, under the influence of beta
      adrenergic receptor stimulation. Transmembrane action potentials were recorded
      from isolated canine left-ventricular midmyocytes at various pacing rates. I(Ks)
      was blocked by HMR1556, I(Kr) by dofetilide. Late I(Na) was augmented by sea
      anemone toxin-II. Isoproterenol was added for beta-adrenergic receptor
      stimulation. BAPTA-AM buffered intracellular Ca(2+). SEA0400 partially inhibited
      the Na(+)-Ca(2+) exchanger. BVR was quantified as variability of action-potential
      duration at 90% repolarization: Sigma(|APD90; i+1 minus APD90; i|)/[nbeatsx
      radical2] for 30 consecutive action potentials. Baseline BVR was significantly
      increased by I(Kr) blockade and late-I(Na) augmentation, especially at slow
      pacing rates. beta-adrenergic stimulation restabilized these BVR changes. In
      contrast, I(Ks) blockade caused very little change in repolarization when
      compared to baseline conditions, but predisposed the myocyte to increased BVR
      during beta-adrenergic stimulation, especially at fast rates. BAPTA-AM and
      SEA0400 reduced this excessive BVR and eliminated early afterdepolarizations. In
      conclusion, beta-adrenergic receptor stimulation exaggerates BVR during I(Ks)
      blockade, indicating a BVR-stabilizing role of beta-adrenergic-sensitive I(Ks).
      Loss of I(Ks) plus overriding of Ca(2+)-dependent membrane currents, including
      inward Na(+)-Ca(2)(+) exchange current, conspire to proarrhythmic BVR under these
      conditions.

PMID- 19744497
TI  - Structural basis for substrate recognition and specificity in aklavinone-11
      hydroxylase from rhodomycin biosynthesis.
AB  - In the biosynthesis of several anthracyclines, aromatic polyketides produced by
      many Streptomyces species, the aglycone core is modified by a specific flavin
      adenine dinucleotide (FAD)- and NAD(P)H-dependent aklavinone-11-hydroxylase.
      Here, we report the crystal structure of a ternary complex of this enzyme from
      Streptomyces purpurascens, RdmE, with FAD and the substrate aklavinone. The
      enzyme is built up of three domains, a FAD-binding domain, a domain involved in
      substrate binding, and a C-terminal thioredoxin-like domain of unknown function.
      RdmE exhibits structural similarity to aromatic hydroxylases from the p
      hydroxybenzoate hydroxylase family, but unlike most other related enzymes, RdmE
      is a monomer. The substrate is bound in a hydrophobic pocket in the interior of
      the enzyme, and access to this pocket is provided through a different route than
      for the isoalloxazine ring of FAD-the backside of the ligand binding cleft. The
      architecture of the substrate binding pocket and the observed enzyme-aklavinone
      interactions provide a structural explanation for the specificity of the enzyme
      for non-glycosylated substrates with C9-R stereochemistry. The isoalloxazine ring
      of the flavin cofactor is bound in the "out" conformation but can be modeled in
      the "in" conformation without invoking large conformational changes of the
      enzyme. This model places the flavin ring in a position suitable for catalysis,
      almost perpendicular to the tetracyclic ring system of the substrate and with a
      distance of the C4a carbon atom of the isoalloxazine ring to the C-11 carbon atom
      of the substrate of 4.8 A. The structure suggested that a Tyr224-Arg373 pair
      might be involved in proton abstraction at the C-6 hydroxyl group, thereby
      increasing the nucleophilicity of the aromatic ring system and facilitating
      electrophilic attack by the perhydroxy-flavin intermediate. Replacement of Tyr224
      by phenylalanine results in inactive enzyme, whereas mutants at position Arg373
      retain catalytic activity close to wild-type level. These data establish an
      essential role of residue Tyr224 in catalysis, possibly in aligning the substrate
      in a position suitable for catalysis.

PMID- 19744498
TI  - Molecular interplay between the replicative helicase DnaC and its loader protein
      DnaI from Geobacillus kaustophilus.
AB  - Helicase loading factors are thought to transfer the hexameric ring-shaped
      helicases onto the replication fork during DNA replication. However, the
      mechanism of helicase transfer onto DNA remains unclear. In Bacillus subtilis,
      the protein DnaI, which belongs to the AAA+ family of ATPases, is responsible for
      delivering the hexameric helicase DnaC onto DNA. Here we investigated the
      interaction between DnaC and DnaI from Geobacillus kaustophilus HTA426 (GkDnaC
      and GkDnaI, respectively) and determined that GkDnaI forms a stable complex with
      GkDnaC with an apparent stoichiometry of GkDnaC(6)-GkDnaI(6) in the absence of
      ATP. Surface plasmon resonance analysis indicated that GkDnaI facilitates loading
      of GkDnaC onto single-stranded DNA (ssDNA) and supports complex formation with
      ssDNA in the presence of ATP. Additionally, the GkDnaI C-terminal AAA+ domain
      alone could bind ssDNA, and binding was modulated by nucleotides. We also
      determined the crystal structure of the C-terminal AAA+ domain of GkDnaI in
      complex with ADP at 2.5 A resolution. The structure not only delineates the
      binding of ADP in the expected Walker A and B motifs but also reveals a
      positively charged region that may be involved in ssDNA binding. These findings
      provide insight into the mechanism of replicative helicase loading onto ssDNA.

PMID- 19744499
TI  - Selection and structure of hyperactive inteins: peripheral changes relayed to the
      catalytic center.
AB  - Inteins are phylogenetically diverse self-splicing proteins that are of great
      functional, evolutionary, biotechnological, and medical interest. To address the
      relationship between intein structure and function, particularly with respect to
      regulating the splicing reaction, and to groom inteins for application, we
      developed a phage display system to extend current in vivo selection for enhanced
      intein function to selection in vitro. We thereby isolated inteins that can
      function under excursions in temperature, pH, and denaturing environment.
      Remarkably, most mutations mapped to the surface of the intein, remote from the
      active site. We chose two mutants with enhanced splicing activity for
      crystallography, one of which was also subjected to NMR analysis. These studies
      define a "ripple effect", whereby mutations in peripheral non-catalytic residues
      can cause subtle allosteric changes in the active-site environment in a way that
      facilitates intein activity. Altered salt-bridge formation and chemical shift
      changes of the mutant inteins provide a molecular rationale for their phenotypes.
      These fundamental insights will advance the utility of inteins in chemical
      biology, biotechnology, and medicine.

PMID- 19744500
TI  - The protective effect of Ganoderma atrum polysaccharide against
      anoxia/reoxygenation injury in neonatal rat cardiomyocytes.
AB  - AIMS: Oxidative stress has been largely implicated in the pathogenesis of
      anoxia/reoxygenation injury. Ganoderma atrum polysaccharide (PSG-1), the most
      abundant component extracted from the fruiting bodies of G. atrum, has been shown
      to possess potent antioxidant activity. In this study, we investigated whether
      PSG-1 attenuates oxidative stress induced by anoxia/reoxygenation injury. MAIN
      METHODS: Primary cultures of neonatal rat cardiomyocytes pretreated with PSG-1
      were exposed to anoxia/reoxygenation and subsequently monitored for cell
      viability by the MTT assay. Lactate dehydrogenase (LDH) release, manganese
      superoxide dismutase (MnSOD), catalase and glutathione peroxidase activities, and
      malondialdehyde contents were determined by a colorimetric method. The levels of
      reactive oxygen species (ROS) and apoptosis were determined by flow cytometry.
      Western blot analysis was used for the determination of MnSOD, catalase and
      glutathione peroxidase expression. KEY FINDINGS: In the present study, PSG-1
      protected the cardiomyocytes from anoxia/reoxygenation injury, as evidenced by
      decreased LDH release and increased cell viability in a dose-dependent manner up
      to 100microg/ml. This protective effect concomitantly decreased malondialdehyde
      contents, while significantly increased the activities and protein expressions of
      MnSOD, catalase and glutathione peroxidase. Furthermore, treatment with PSG-1
      decreased ROS production and apoptosis in cardiomyocytes undergoing
      anoxia/reoxygenation. SIGNIFICANCE: The present study first demonstrates that PSG
      1 protects cardiomyocytes against oxidative stress induced by
      anoxia/reoxygenation by attenuating ROS production, apoptosis and increasing
      activities and protein expressions of endogenous antioxidant enzymes.

PMID- 19744501
TI  - Mutagenesis in vivo in T cells of p21-deficient mice.
AB  - Mice that are deficient in p53 exhibit an early onset of multiple types of
      tumors, especially thymic lymphoma. However, it remains unclear to what extent
      each of the p53-regulated pathways exerts its tumor suppressor activity.
      p21(Cip1/Waf1), acting down stream of p53, is a major G1/S checkpoint protein
      that restricts cell cycle progression into S phase in the presence of DNA damage.
      While at old ages p21-/- mice have a higher incidence of many types of tumors
      than p21+/+ mice, they are more resistant to thymic lymphomagenesis. In this
      study, we characterized mutagenesis in vivo in T cells of p21-deficient mice,
      using loss of heterozygosity (LOH) at Aprt locus as an indicator. We found that
      the spontaneous Aprt mutant frequency in T cells of p21-/- mice is lower than
      that in p21+/+ mice. The mutational spectra, however, are similar, with mitotic
      recombination being the predominant pathway. In contrast to the remarkable
      induction of LOH events in T cells of p53-/- mice exposed to X-rays, LOH in T
      cells of p21-/- mice is not significantly induced by X-rays. Correspondingly,
      lymphoid cells of p21-/- mice are more sensitive to IR-induced apoptosis than
      those of p21+/+ mice, in contrast to the radioresistance of p53-deficient
      lymphocytes. Reduction in mutation load in T cell lineages may contribute to the
      suppression of thymic lymphomagenesis in p21-/- mice.

PMID- 19744502
TI  - Nefopam but not physostigmine affects the thermoregulatory response in mice via
      alpha(2)-adrenoceptors.
AB  - Nefopam, a non-opioid, centrally acting benzoxazocine analgesic, proved to be as
      efficient in treatment of postanaesthetic thermoregulatory shivering as clonidine
      or meperidine. However, its exact mechanism of action is still unclear. Potent
      anti-shivering activity was also demonstrated for physostigmine primarily based
      on cholinergic but probably also different additional mechanisms of action.
      Hypothesizing an involvement of alpha(2)-adrenoceptors we studied their role in
      nefopam- and physostigmine-mediated thermoregulation in a mouse model of
      nonshivering thermogenesis. To differentiate possible alpha(2)-adrenoceptor
      subtype-specific interactions, we analysed wildtype mice and mice with deletion
      of the alpha(2A)-, alpha(2B)- or alpha(2C)-adrenoceptor (knock out). Ten mice of
      each genotype (n = 40) were administered saline, saline plus atipamezole, 1 mg/kg
      nefopam, 25 mg/kg nefopam, 25 mg/kg nefopam plus atipamezole, physostigmine and
      physostigmine plus atipamezole intraperitoneally. Each mouse was randomly
      subjected to each of the seven different treatments. Afterwards, the mice were
      positioned into a plexiglas chamber where rectal temperature and mixed expired
      carbon dioxide were measured during following whole body cooling.
      Thermoregulatory threshold temperature of nonshivering thermogenesis and maximum
      response intensity were analysed. Nefopam decreased the thermoregulatory
      threshold temperature in wildtype, alpha(2B)- and alpha(2C)-adrenoceptor mice.
      This effect was partially abolished by additional administration of the alpha(2)
      adrenoceptor antagonist atipamezole. In alpha(2A)-adrenoceptor knock out mice,
      nefopam did not affect the thermoregulatory threshold. In contrast, physostigmine
      decreased the thermoregulatory threshold in wildtype and all alpha(2)
      adrenoceptor knock out mice independently from additional atipamezole
      administration. Our results indicate an important role of the alpha(2A)
      adrenoceptor in the thermoregulatory response induced by nefopam but not by
      physostigmine in mice.

PMID- 19744503
TI  - Rg1 protects the MPP+-treated MES23.5 cells via attenuating DMT1 up-regulation
      and cellular iron uptake.
AB  - Ginsenoside-Rg1 is one of the pharmacologically active component isolated from
      ginseng. Our previous study observed the protective effect of Rg1 on iron
      accumulation in the substantia nigra (SN) in 1-methyl-4-phenyl-1,2,3,6-
      tetrahydropyridine (MPTP)-treated Parkinson's disease (PD) mice. However, the
      mechanisms of this neuroprotective effect of Rg1 are unknown. In this study, we
      elucidated possible mechanisms for this effect using 1-methyl-4-phenylpyridinium
      (MPP(+))-treated MES23.5 cells. Previous study showed MPP+ treatment induced up
      regulation of divalent metal transporter 1 without iron responsive element (DMT1
      IRE) in MES23.5 cells. In the present study, we observed that pretreatment with
      Rg1 could inhibit MPP+-induced up-regulation of DMT1-IRE in MES23.5 cells. Up
      regulation of DMT1-IRE by MPP+ treatment was associated with ROS production and
      translocation of nuclear factor-kappaB (NF-kappaB) to nuclei, both of which were
      significantly inhibited by Rg1 pretreatment. The role of ROS and NF-kappaB in the
      up-regulation of DMT1-IRE was supported by application of an antioxidant NAC and
      BAY 11-7082, an inhibitor of IkappaBalpha phosphorylation. Furthermore, we also
      showed Rg1 could decrease DMT1-mediated ferrous iron uptake and iron-induced cell
      damage by inhibiting the up-regulation of DMT1-IRE. These results indicate that
      Rg1 protected the MPP+-treated MES23.5 cells via attenuating DMT1-IRE up
      regulation likely through inhibition of ROS-NF-kappaB pathway; Attenuation of
      DMT1-IRE expression decreased the iron influx and iron-induced oxidative stress.

PMID- 19744504
TI  - Changing patterns of daily rhythmicity across reproductive states in diurnal
      female Nile grass rats (Arvicanthis niloticus).
AB  - A suite of changes in circadian rhythms have been described in nocturnal rodents
      as females go through pregnancy and lactation, but there is no information on
      such patterns in diurnal species. As the challenges faced by these two groups of
      animals are somewhat different, we characterized changes in activity and core
      body temperature (T(b)) in female diurnal Nile grass rats (Arvicanthis niloticus)
      as they went through a series of reproductive states: virgin, pregnant, pregnant
      and lactating, lactating only, and post-weaning. The phase of neither rhythm
      varied, but the amplitude did. Females increased their overall levels of daily
      activity from early to late pregnancy, regardless of whether they were also
      lactating. The pattern of activity was less rhythmic during early than mid
      lactation, in both non-pregnant and pregnant females, as a consequence of a
      decrease in daytime relative to nighttime activity. The T(b) rhythm amplitude
      dropped from mid-pregnancy through mid-lactation, and there were rises in T(b)
      troughs during the mid-light and mid-dark phases of the day, though pregnancy and
      lactation affected T(b) at these times in somewhat different ways. This study
      demonstrates that rhythms in diurnal grass rats change during pregnancy and
      lactation in different ways than those of nocturnal species that have been
      studied to date and that the effects of pregnancy and lactation are not additive
      in any simple way.

PMID- 19744505
TI  - Patulin-induced oxidative DNA damage and p53 modulation in HepG2 cells.
AB  - Patulin (PAT) is a mycotoxin produced by certain species of Penicillium and
      Aspergillus. The aim of this study was to assess PAT-induced DNA damage and to
      clarify the mechanisms, using human hepatoma G2 (HepG2) cells. PAT caused
      significant increase of DNA migration in single cell gel electrophoresis assay.
      To elucidate the role of glutathione (GSH), the intracellular GSH level was
      modulated by pre-treatment with buthionine-(S, R)-sulfoximine, a specific GSH
      synthesis inhibitor. It was observed that PAT significantly induced DNA damage in
      GSH-depleted HepG2 cells at lower concentrations. PAT induced the increased
      levels of reactive oxygen species and depletion of GSH in HepG2 cells using 2,7
      dichlorofluorescein diacetate and 0-phthalaldehyde, respectively. PAT
      significantly increased the levels of 8-hydroxydeoxyguanosine and thiobarbituric
      acid-reactive substances in HepG2 cells. Also, PAT-induced p53 protein
      accumulation was observed in HepG2 cells, suggesting that the activation of p53
      appeared to have been a downstream response to the PAT-induced DNA damage. These
      results demonstrate that PAT causes DNA strand breaks in HepG2 cells, probably
      through oxidative stress. Both GSH, as a main intracellular antioxidant, and p53
      protein are responsible for cellular defense against PAT-induced DNA damage.

PMID- 19744506
TI  - Limited expansion of virus-specific CD8 T cells in the aged environment.
AB  - The mechanisms responsible for the diminished immune response seen with aging are
      unclear. In this study, we investigate the contributions of alterations in the
      lymphoid microenvironment to this decrease. Using adoptive transfer of virus
      specific transgenic CD8 T cells, we demonstrate that the aged environment
      inhibits the clonal expansion of specific CD8 T cells from young mice during
      virus infection. Transferred specific CD8 T cells from young mice demonstrated a
      response reflecting the CD8 T cell response of the intact aged host: the CD8 T
      cells expand more slowly and have a decreased maximal expansion in an aged
      compared to a young environment. While isolated DCs (MHC II(+) CD11c(+)) of aged
      mice maintain their ability to support CD8 T cell Ag-specific expansion in vitro,
      splenocytes demonstrated an age-associated decrease in this ability. Since the
      percentages of various populations of DCs in splenocytes demonstrate no
      significant alteration with age, this diminished APC activity of splenocytes of
      aged mice may reflect inhibitory activity of other cell populations. The results
      of this study demonstrate that elements of the aged environment play an important
      role in the alteration of T cell response to virus infection in the aged.

PMID- 19744507
TI  - Effect of electronic time monitors on children's television watching: pilot trial
      of a home-based intervention.
AB  - OBJECTIVES: This pilot study evaluated the feasibility (recruitment, retention,
      and acceptability) and preliminary efficacy of a six-week home-based electronic
      time monitor intervention on New Zealand children's television watching in 2008.
      METHODS: Twenty-nine children aged 9 to 12 years who watched more than 20 h of
      television per week (62% male, mean age 10.4 years) were randomised to either the
      intervention or the control group. The intervention group received an electronic
      TV time monitor for 6 weeks and advice to restrict TV watching to 1 h per day or
      less. The control group was given verbal advice to restrict TV watching. RESULTS:
      Participant retention at 6 weeks was 93%. Semi-structured interviews with
      intervention families confirmed moderate acceptability of TV time monitors and
      several perceived benefits including better awareness of household TV viewing and
      improved time planning. Drawbacks reported included disruption to parents' TV
      watching and increased sibling conflict. Time spent watching television decreased
      by 4.2 h (mean change [SD]: -254 [536] min) per week in the intervention group
      compared with no change in the control group (-3 [241] min), but the difference
      between groups was not statistically significant, p=0.77. Both groups reported
      decreases in energy intake from snacks and total screen time and increases in
      physical activity measured by pedometer and between-group differences were not
      statistically significant. CONCLUSIONS: Electronic TV time monitors are feasible
      to use for home-based TV watching interventions although acceptability varies
      between families. Preliminary findings from this pilot suggest that such devices
      have potential to decrease children's TV watching but a larger trial is needed to
      confirm effectiveness. Future research should be family-orientated; take account
      of other screen time activities; and employ TV time monitors as just one of a
      range of strategies to decrease sedentary behaviour.

PMID- 19744508
TI  - Association between physical activity and insulin resistance in Iranian adults:
      National Surveillance of Risk Factors of Non-Communicable Diseases (SuRFNCD
      2007).
AB  - BACKGROUND: Insulin resistance is an underlying mechanism of metabolic syndrome.
      We attempted to determine the association between physical activity and insulin
      resistance in Iranian adults. METHODS: The data of the third national
      Surveillance of Risk Factors of Non-Communicable Diseases (SuRFNCD-2007) in Iran
      were used. We ran the Global Physical Activity Questionnaire (GPAQ) over a
      nationally representative sample of 3101 adults. Total physical activity (TPA)
      was calculated using metabolic equivalents (MET) for intensity of physical
      activities. Insulin resistance was measured by the homeostasis model assessment
      of insulin resistance (HOMA-IR). RESULTS: When physical activity was classified
      into high, moderate, and low categories, HOMA-IR values significantly increased
      from the high category to the moderate and low categories (p<0.01). After
      adjustment for age, area of residence, smoking, and body mass index (BMI), TPA
      (r=-0.26, p<0.01 in males and r=-0.21, p<0.01 in females), duration of vigorous
      intensity activity (r=-0.28, p<0.01 in males and r=-0.18, p=0.01 in females),
      duration of moderate-intensity activity (r=-0.16, p=0.01 in males and r=-0.17,
      p<0.01 in females), and the time spent on sedentary behaviors (r=0.16, p=0.01 in
      males and r=-0.22, p<0.01 in females) were significantly correlated to HOMA-IR.
      The prevalence of physical inactivity increased linearly with increasing HOMA-IR
      quintiles. CONCLUSIONS: Our findings indicate a significant relationship between
      physical inactivity and insulin resistance. For communities in a transition phase
      of lifestyle, encouraging physical activity may help prevent insulin resistance
      and its adverse consequences.

PMID- 19744509
TI  - Psychosocial predictors of adherence to risk-appropriate cervical cancer
      screening guidelines: a cross sectional study of women in Ohio Appalachia
      participating in the Community Awareness Resources and Education (CARE) project.
AB  - OBJECTIVE: We describe factors, in the context of the Social Determinants of
      Health model, associated with receiving Pap smears within risk-appropriate
      guidelines (i.e., guidelines that specify screening intervals based upon a
      woman's individual risk of developing cervical cancer). METHODS: Completed in
      June 2006, we conducted a cross-sectional survey of women from 14 health clinics
      in Ohio Appalachia pertaining to psychosocial, demographic, biological, and
      health-related factors. A logistic regression model was constructed to predict
      whether or not a woman was within risk-appropriate cervical cancer screening
      guidelines. RESULTS: Of 562 women with a date of last Pap smear, 380 (68%) were
      within risk-appropriate guidelines. Logistic regression showed that, compared to
      women with low-level SES, women with middle- and high-level SES had 3.39 [1.85,
      6.21] and 3.86 [2.03, 7.34] times the odds, respectively, of being within risk
      appropriate guidelines. Odds of being within guidelines increased 1.09 [1.04,
      1.15] fold for each decrease of one major life event. Additionally, women that
      were financially better off or financially worse off than their parents at the
      same age had lower odds (0.41 [0.23, 0.73] and 0.49 [0.24, 0.98], respectively)
      of being within guidelines than women who reported their finances were the same
      as their parents. Results also showed an interaction between marital status and
      age at first intercourse (p=0.001). CONCLUSION: The results suggest an impact of
      psychosocial factors on Pap smear testing behaviors, and illustrate the need to
      examine risk-appropriate interventions to improve screening.

PMID- 19744510
TI  - The meta-volition model: organizational leadership is the key ingredient in
      getting society moving, literally!
AB  - This paper argues that substantive and sustainable population-wide improvements
      in physical activity can be achieved only through the large scale adoption and
      implementation of policies and practices that make being active the default
      choice and remaining inactive difficult. Meta-volition refers to the volition and
      collective agency of early adopter leaders who implement such changes in their
      own organizations to drive productivity and health improvements. Leaders,
      themselves, are motivated by strong incentives to accomplish their organizational
      missions. The meta-volition model (MVM) specifies a cascade of changes that may
      be sparked by structural integration of brief activity bouts into organizational
      routine across sectors and types of organizations. MVM builds upon inter
      disciplinary social ecological change models and frameworks such as diffusion of
      innovations, social learning and social marketing. MVM is dynamic rather than
      static, integrating biological influences with psychological factors, and socio
      cultural influences with organizational processes. The model proposes six levels
      of dissemination triggered by organizational marketing to early adopter leaders
      carried out by "sparkplugs," boisterous leaders in population physical activity
      promotion: initiating (leader-leader), catalyzing (organizational-individual),
      viral marketing (individual-organizational), accelerating (organizational
      organizational), anchoring (organizational-community) and institutionalizing
      (community-individual). MVM embodies public-private partnership principles, a
      collective investment in the high cost of achieving and maintaining active
      lifestyles.

PMID- 19744511
TI  - Development of the Community Healthy Living Index: a tool to foster healthy
      environments for the prevention of obesity and chronic disease.
AB  - OBJECTIVES: This paper presents a new, comprehensive tool for communities to
      assess opportunities for active living and healthy eating and to mobilize all
      sectors of society to conquer obesity and chronic disease. METHOD: Relevant
      existing tools and input from an expert panel were considered to draft the
      Community Healthy Living Index (CHLI). CHLI covers five major sectors where
      people live, work, learn, and play: schools, afterschools, work sites,
      neighborhoods, and the community-at-large. CHLI and the accompanying procedures
      enable community teams to assess programs, the physical environment, and policies
      related to healthy living and to plan improvement strategies. In 2008, with local
      YMCAs acting as conveners, community assessment teams from six US communities
      pilot-tested CHLI for cognitive response testing, inter-rater reliability, and
      implementation feasibility. CHLI was revised to reflect the test results.
      RESULTS: Pilot analyses demonstrated that the process was feasible, with most
      questions being interpreted as intended and showing substantial to almost perfect
      agreement between raters. The final CHLI is being disseminated nationally.
      CONCLUSIONS: Preliminary data illustrate CHLI obtains reliable results and is
      feasible to implement. CHLI is a promising tool for community-based prevention
      efforts to draw attention to opportunities for healthy living and create impetus
      for community changes.

PMID- 19744512
TI  - Merging long range transportation planning with public health: a case study from
      Utah's Wasatch Front.
AB  - OBJECTIVE: US transportation systems have been identified as a problem for public
      health, as they often encourage automobile transportation and discourage physical
      activity. This paper provides a case study examination of the Public Health
      Component of the Wasatch Front Regional Council's Regional Transportation Plan.
      This plan provides an example of what transportation planners at Utah's largest
      metropolitan planning organization (MPO) are doing to encourage physical activity
      through transportation. METHODS: Existing active living research was used to
      guide recommendations using a process that included a comprehensive literature
      review and a review of existing state programs, advisory group and stakeholder
      meetings, and policy recommendations based on existing local conditions. RESULTS:
      Stakeholders from a diversity of background and interests came together with one
      common goal: to improve public health. Based on this collaborative process, nine
      policy approaches were specifically recommended for approval and integration in
      the Wasatch Front Regional Transportation Plan. CONCLUSION: By using current
      research as a guide and integrating a variety of interests, the Wasatch Front
      Regional Council is setting a new standard for a collaborative multi-modal focus
      in transportation planning, which can be replicated nationwide.

PMID- 19744513
TI  - Rural and urban park visits and park-based physical activity.
AB  - OBJECTIVE: A physical activity disparity exists between rural and urban
      residents. Community parks are resources for physical activity because they are
      publicly provided, available at a low cost, and accessible to most residents. We
      examine the use of and physical activity outcomes associated with rural and urban
      parks. METHODS: Onsite observations were conducted using the System for Observing
      Play and Recreation in Communities (SOPARC) at four rural and four urban parks.
      Momentary sampling scans were conducted four times per day for seven days at each
      site. RESULTS: A total of 6,545 park visitors were observed. Both rural and urban
      park visitors were observed more often at larger parks with paved trails and
      attended most often on weekends. Rural park visits were more frequent than urban
      park visits but rural visits were less physically active. CONCLUSION: Although
      similarities were observed between rural and urban park visits, differences
      suggest that findings from park and physical activity studies in urban areas
      should not be considered representative of their rural counterparts. Given that
      the majority of existing park and physical activity research has been undertaken
      in urban settings, the need for complementary research in rural settings has been
      made evident through this presentation of baseline descriptive data.

PMID- 19744514
TI  - Walking trips to parks: exploring demographic, environmental factors, and
      preferences for adults with children in the household.
AB  - OBJECTIVES: (1) To understand demographic and environmental factors influencing
      walking trips to parks for adults with children living at home; and (2) To
      determine if preferences for walking environments may influence walking trips and
      why. METHODS: Neighborhoods with varying levels of canopy coverage and access to
      destinations were selected within the city of Seattle, Washington and surrounding
      suburbs. Walking trip frequency, preferences for walking environments, and
      demographic information were measured through a postal survey in fall 2006 (21%
      response rate, N=617; 41% adults with children living in the household, n=250).
      Analysis of variance and multiple linear regressions were used to test the
      associations between variables. Chi-square and qualitative content analysis were
      used to understand preferences for walking environments. RESULTS: Adult
      respondents with children living at home walked most frequently to parks compared
      to other destinations. Owning a dog, living within close proximity to a variety
      of destinations, perceptions of ample neighborhood vegetation, and preference for
      natural-looking environments were factors positively associated with these
      walking trips. CONCLUSIONS: Demographic and environmental factors influence
      walking trips, particularly perceived level of neighborhood vegetation and
      individual preferences. However, highly vegetated walking environments also
      elicited concerns about safety for some respondents.

PMID- 19744515
TI  - Human gamma-band activity: a review on cognitive and behavioral correlates and
      network models.
AB  - Gamma-band oscillations (roughly 30-100 Hz) in human and animal EEG have received
      considerable attention in the past due to their correlations with cognitive
      processes. Here, we want to sketch how some of the higher cognitive functions can
      be explained by memory processes which are known to modulate gamma activity.
      Especially, the function of binding together the multiple features of a perceived
      object requires a comparison with contents stored in memory. In addition, we
      review recent findings about the actual behavioral relevance of human gamma-band
      activity. Interestingly, rather simple models of spiking neurons are not only
      able to generate oscillatory activity within the gamma-band range, but even show
      modulations of these oscillations in line with findings from human experiments.

PMID- 19744516
TI  - Modeling dad: animal models of paternal behavior.
AB  - In humans, paternal behaviors have a strong influence on the emotional and social
      development of children. Fathers, more frequently than mothers, leave the family
      nucleus, and/or become abusive, leading to offspring that are more likely to grow
      under stressful conditions and greater susceptibility to abnormal health and
      social outcomes. Literature on parental behaviors, human or animal, has primarily
      focused on the interactions between mothers and offspring, with little research
      directed at understanding paternal behavior. In animal studies, experimenters
      correlate paternal behaviors with those seen in rodent or primate mothers, often
      under situations in which behaviors such as nest protection, huddling, pup
      grooming, and retrieval are artificially induced. In humans, the majority of the
      studies have looked at paralleling hormonal changes in fathers with those
      occurring in mothers, or observed paternal behaviors in populations with specific
      anthropological backgrounds. These studies reveal commonalities in parental
      behaviors and their underlying neural circuits. However, this work highlights the
      possibility that paternal behavior has components that are strictly masculine
      with unique neurobiological mechanisms. This review summarizes this information
      and provides a current view of a topic that needs further exploration.

PMID- 19744517
TI  - Neuroprotective efficacy of Bacopa monnieri against rotenone induced oxidative
      stress and neurotoxicity in Drosophila melanogaster.
AB  - Bacopa monnieri, Linn. (Brahmi, BM), traditionally used to improve mental health
      in Indian ayurvedic system of medicine is known to possess various
      neuropharmacolgical properties. In the recent past, Drosophila has been widely
      used as a model to study various neurodegenerative diseases. Environmental toxins
      like rotenone, a specific inhibitor of complex I is employed to increase
      oxidative stress mediated neuropathology and sporadic Parkinson's disease. In
      this study, we examined the neuroprotective properties of BM against rotenone
      induced oxidative damage and neurotoxicity. Flies (Oregon K strain, adult males)
      exposed to a standardized BM powder for 7 days in the diet exhibited significant
      diminution in the levels of endogenous oxidative markers viz., malondialdehyde,
      hydroperoxide and protein carbonyl content. Further, BM offered complete
      protection against rotenone (500 microM) induced oxidative stress and markedly
      inhibited dopamine depletion (head region, 33%; body region, 44%) in flies. Flies
      exposed to rotenone+BM exhibited a lower incidence of mortality (40-66%
      protection) and performed better in a negative geotaxis assay (45-65%) both
      suggesting the neuroprotective potential of BM. Interestingly, BM also conferred
      significant resistance (43-54% protection) in a paraquat oxidative stress
      bioassay. The neuroprotective effects of BM were highly comparable to those of a
      commercially available Brahmi preparation. Although the precise mechanism/s
      underlying the neuroprotective efficacy of BM are not clear, it is hypothesized
      that it is wholly or in part related to its ability to mitigate rotenone induced
      oxidative stress. Further, our approach confirms the utility of the Drosophila
      model in screening putative neuroprotective phytomedicines prior to their use in
      mammalian models.

PMID- 19744518
TI  - Resveratrol inhibits beta-amyloid oligomeric cytotoxicity but does not prevent
      oligomer formation.
AB  - Beta-amyloid (Abeta) aggregation has been strongly associated with the
      neurodegenerative pathology and a cascade of harmful event rated to Alzheimer's
      disease (AD). Inhibition of Abeta assembly, destabilization of preformed Abeta
      aggregates and attenuation of the cytotoxicity of Abeta oligomers and fibrils
      could be valuable therapeutics of patients with AD. Recent studies suggested that
      moderate consumption of red wine and intake of dietary polyphenols, such as
      resveratrol, may benefit AD phenotypes in animal models and reduce the relative
      risk for AD clinical dementia. To understand the mechanism of this
      neuroprotection, we studied the effects of resveratrol, an active ingredient of
      polyphenols in wine and many plants, on the polymerization of Abeta42 monomer,
      the destabilization of Abeta42 fibril and the cell toxicity of Abeta42 in vitro
      using fluorescence spectroscopic analysis with thioflavin T (ThT), transmission
      electron microscope (TEM), circular dichroism (CD) and MTT assay. The results
      showed that resveratrol could dose-dependently inhibit Abeta42 fibril formation
      and cytotoxicity but could not prevent Abeta42 oligomerization. The studies by
      Western-blot, dot-blot and ELISA confirmed that the addition of resveratrol
      resulted in numerous Abeta42 oligomer formation. In conjunction with the concept
      that Abeta oligomers are linked to Abeta toxicity, we speculate that aside from
      potential antioxidant activities, resveratrol may directly bind to Abeta42,
      interfere in Abeta42 aggregation, change the Abeta42 oligomer conformation and
      attenuate Abeta42 oligomeric cytotoxicity.

PMID- 19744519
TI  - Excess mortality, length of stay and cost attributable to candidaemia.
AB  - BACKGROUND: There were 1967 reports of Candida species isolated from blood
      specimens in 2007 in the UK (excluding Scotland). Such infections are
      particularly common in the intensive care unit (ICU). The impact of candidaemia
      on mortality, length of stay (LOS) and cost in a UK hospital was examined.
      METHODS: A retrospective analysis of candidaemia episodes and appropriate matched
      controls was undertaken based on data from the ICU, high dependency units and
      hospital wards at Wythenshawe Hospital in Manchester. The study covered the
      period November 2003-February 2007. RESULTS: In total, 48 case-patients of
      candidaemia and 81 control-patients were identified. The attributable mortality
      due to candidaemia varied from 21.5% to 34.7%. Candidaemia patients spend on
      average 5.6 days more in the ICU than matched patients and generate mean
      additional costs of at least 8252 UK pounds per patient, 16,595 pounds in adults
      only. CONCLUSION: Candidaemia remains a severe disease associated with high
      attributable mortality in the UK. In addition, candidaemia leads to additional
      ICU length of stay and costs. The implication is an attributable cost of at least
      16.2 million UK pounds with 683 deaths attributable to candidaemia per year in
      the UK.

PMID- 19744520
TI  - Short-term regulation of organic anion transporters.
AB  - Organic anion transporters (OATs), which belong to the superfamily SLC22A, are
      key determinants in the absorption, distribution, and excretion of a diverse
      array of environmental toxins, and clinically important drugs, and, therefore,
      are critical for the survival of mammalian species. Alteration in the function of
      these drug transporters plays important roles in intra- and inter-individual
      variability of the therapeutic efficacy and the toxicity of many drugs. As a
      result, the activity of OATs must be under tight regulation so as to carry out
      their normal functions. This review article highlights the recent advances from
      our laboratory as well as from others in delineating the short-term regulation of
      OATs. These advances provide important insights into strategies to maximize
      therapeutic efficacy in drug development.

PMID- 19744521
TI  - A combined histological and MRI brain atlas of the common marmoset monkey,
      Callithrix jacchus.
AB  - The common marmoset, Callithrix jacchus, is of growing importance for research in
      neuroscience and related fields. In the present work, we describe a combined
      histological and magnetic resonance imaging (MRI) atlas constructed from the
      brains of two adult female marmosets. Histological sections were processed from
      Nissl staining and digitized to produce an atlas in a large format that
      facilitates visualization of structures with significant detail. Naming of
      identifiable brain structures was performed utilizing current terminology. The
      histological sections and a simplified schematic atlas are available online at
      http://udn.nichd.nih.gov/brainatlas_home.html.

PMID- 19744523
TI  - Pharmacogenetics of antiretrovirals.
AB  - The introduction of highly active antiretroviral therapy (HAART) as standard of
      care has changed the natural history of HIV infection into a manageable chronic
      disease requiring long-term antiretroviral (ARV) treatment. However, response to
      HAART is often limited by the occurrence of toxicity or by the emergence of drug
      resistance. Antiretroviral treatment is characterized by differing rates of
      adverse events and responses. Genetic variations between human beings account for
      a relevant proportion of this variability. A relevant number of associations
      between human genetic variants and predisposition to adverse events have been
      described and for some antiretroviral drugs a clear and casual genotype-phenotype
      correlation has already been established. The strong association between abacavir
      hypersensitivity reaction and HLA-B*5701 has been demonstrated in both
      observational and blinded randomized clinical trials in racially diverse
      populations and represents the best example of the clinical utility of
      pharmacogenetic screening in HIV medicine. Genotyping for HLA-B*5701 before
      prescribing an abacavir containing regimen has been introduced into routine
      clinical practice as the standard of care for all patients. Other well
      established associations include CYP2B6 alleles and efavirenz central nervous
      system side effects, UGT1A1 alleles and atazanavir-associated hyperbilirubinemia
      and HLA class II allele HLA-DRB*0101 and nevirapine-associated hypersensitivity.
      Despite genetic associations having been described for peripheral neuropathy,
      lipodystrophy, hyperlipidaemia, pancreatitis and renal proximal tubulopathy,
      numerous barriers exist to the successful introduction of widespread genetic
      testing to the clinic. Future prospects point in the direction of
      individualization of antiretroviral therapy through insights from host genetics.
      The present paper is aimed to provide a comprehensive review of the published
      literature and to summarize the state of research in this area. This article
      forms part of a special issue of Antiviral Research marking the 25th anniversary
      of antiretroviral drug discovery and development, Vol 85, issue 1, 2010.

PMID- 19744524
TI  - Dysfunction of muscarinic acetylcholine receptors as a substantial basis for
      progressive neurological deterioration in GM3-only mice.
AB  - To examine the effects of deletion of gangliosides on the nervous system by
      avoiding masking effects with the remaining structures, we established double
      knockout (DKO) mice of GM2/GD2 synthase and GD3 synthase genes, i.e., GM3-only
      mice. They showed progressive sensory and motor neuron deficits with aging. We
      further examined higher order neurological functions, and found progressive
      dysfunction of motor coordination with rota-rod test and marked deterioration in
      memory and learning with eight-arm radial maze test in the DKO mice. The results
      of oxotremorine treatment suggested that they undergo strong suppression of
      muscarinic type acetylcholine receptors (mAChRs) functions, and that the damage
      in the GM3-only mice is due to a mAChR receptor deficit. On the other hand,
      expression levels of mRNAs of mAChRs were generally up-regulated, suggesting
      compensatory increase of expression due to reduced functions. Since central
      mAChRs are involved in the regulation of cognitive, behavioral, sensory, motor,
      and autonomic functions, we investigated changes in the expressions levels of
      subtypes of the mAChR genes in various regions of brain tissues. M1 and M4
      receptors were conspicuously up-regulated in cortex and striatum in the DKO,
      suggesting that suppressed functions of mAChRs are responsible for the altered
      neurological features, in particular for deteriorated memory and learning,
      observed in the behavioral analyses. Thus, dysfunction of mAChRs might be a
      substantial basis for the progressive neurological deterioration in DKO mice.

PMID- 19744525
TI  - Delayed changes of sleep duration after rewarded olfactory discrimination
      learning in the rat.
AB  - The aim of this experiment was to determine if a task of associative olfactory
      learning, based on the ethological repertory of rats and learnt rapidly in 5
      successive trials, could modify slow wave sleep (SWS) and/or paradoxical sleep
      (PS) duration after learning and/or after a retrieval-reactivation test 24 h
      later. Somnopolygraphic recordings were performed for 20 h per day on trained and
      control (submitted to a pseudo-learning test) rats. SWS and PS durations were
      analyzed per 20 h and per 4 h time-periods. Compared to control rats, after
      learning, trained rats showed a significant increase in SWS duration
      counterbalanced by a significant decrease in wake duration focused on the 5-8 h
      post-training time-window and a significant decrease in PS duration during the 17
      20 h post-training time-window. After the retrieval-reactivation test trained
      rats only showed a decreased PS duration compared to control rats submitted to a
      pseudo-retrieval test. Thus, a rather simple learning task succeeded in eliciting
      an increase in SWS duration in a limited time-window. As the learning task used
      can be compared to human associate-paired learning, this result sustains the
      hypothesis of a link between declarative memory and SWS. In control rats, changes
      in PS duration might be linked to odorized-environment exposure.

PMID- 19744522
TI  - The impact of vascular burden on late-life depression.
AB  - Small vessel pathology and microvascular lesions are no longer considered as
      minor players in the fields of cognitive impairment and mood regulation. Although
      frequently found in cognitively intact elders, both neuroimaging and
      neuropathological data revealed the negative impact on cognitive performances of
      their presence within neocortical association areas, thalamus and basal ganglia.
      Unlike cognition, the relationship between these lesions and mood dysregulation
      is still a matter of intense debate. Early studies focusing on the role of
      macroinfarct location in the occurrence of post-stroke depression (PSD) led to
      conflicting data. Later on, the concept of vascular depression proposed a
      deleterious effect of subcortical lacunes and deep white matter demyelination on
      mood regulation in elders who experienced the first depressive episode. More
      recently, the chronic accumulation of lacunes in thalamus, basal ganglia and deep
      white matter has been considered as a strong correlate of PSD. We provide here a
      critical overview of neuroimaging and neuropathological sets of evidence
      regarding the affective repercussions of vascular burden in the aging brain and
      discuss their conceptual and methodological limitations. Based on these
      observations, we propose that the accumulation of small vascular and
      microvascular lesions constitutes a common neuropathological platform for both
      cognitive decline and depressive episodes in old age.

PMID- 19744526
TI  - Is it safe? Voles in an unfamiliar dark open-field divert from optimal security
      by abandoning a familiar shelter and not visiting a central start point.
AB  - Open-field behavior is a common tool in studying exploration and navigation, as
      well as emotions and motivations. However, it has been suggested that this
      behavior might be parsimoniously interpreted as directed to optimize security,
      with no need to interpret the animal's mental state. This latter view was
      challenged here by providing voles with presumably sense of optimal security. For
      this, voles were introduced into a dark open-field inside a familiar shelter in
      which they previously lived in their home cage. Voles then emerged either to
      locomote only in the vicinity of the shelter, or to travel further out to explore
      the entire arena and only later to return to the shelter. While their staying
      near the shelter confirms the notion of optimizing security, their traveling
      further out along the perimeter negates this notion. This divergence of behavior
      under the same security conditions illustrates that open-field behavior, which is
      a multi-faceted and dynamic process, is also affected by an emotional component.
      That is, safety is a subjective emotional state dictated by various inputs and,
      therefore, the resulting dynamic behavior, which is the ultimate output of the
      central nervous system, may vary beyond the possibility of being parsimoniously
      interpreted by only one factor. In a similar vein, we show that the impact of the
      start point on the paths of locomotion is not an intrinsic property of that
      point, but depends on its physical location.

PMID- 19744527
TI  - Kindled seizure in the prefrontal cortex activated behavioral hyperactivity and
      increase in accumbens gamma oscillations through the hippocampus.
AB  - In previous studies, we reported that a single afterdischarge (AD) or repeated
      ADs (kindling) in the hippocampus resulted in schizophrenia-like behaviors such
      as hyperactivity and loss of sensorimotor gating. Given that medial prefrontal
      cortex (PFC) dysfunction is also found in models of schizophrenia, we
      hypothesized that a single AD in the PFC induces postictal hyperactivity, and PFC
      kindling results in loss in prepulse inhibition (PPI). An AD was induced by
      stimulating the PFC with a 5s stimulus train of 60 Hz frequency and 600-800
      microA intensity. An initial AD evoked in the PFC was not accompanied by clear
      postictal behavioral change. After partial kindling (11+/-2 ADs) of the PFC, the
      PFC-AD propagated into the hippocampus and nucleus accumbens (NAC) and postictal
      hyperactivity lasted > 5 min. The postictal hyperactivity was accompanied by
      increased gamma EEG oscillations in both PFC and NAC. A single AD in hippocampal
      CA1 also induced > 5 min of postictal hyperactivity and increased gamma
      oscillations in the NAC and the PFC, with a transient increase in hippocampus-NAC
      gamma coherence occurring 2-3 min after a hippocampal AD. Electrolytic lesion or
      inactivation of the dorsal hippocampus abolished the behavioral hyperactivity and
      the NAC/PFC gamma wave increase induced by a PFC-AD. Kindling of the PFC (21 ADs)
      but not of the lateral frontal cortex resulted in a deficit of PPI to the
      acoustic startle response tested 3 days after the last AD. In summary, gamma
      waves in the NAC were found to accompany postictal hyperactivity induced by an AD
      in the PFC. Postictal gamma and hyperactivity required an intact hippocampus,
      perhaps through the hippocampal-NAC pathway. PFC kindling, similar to hippocampal
      CA1 kindling, resulted in a prolonged deficit in PPI.

PMID- 19744528
TI  - Implication of beta3-adrenoceptors in the antidepressant-like effects of
      amibegron using Adrb3 knockout mice in the chronic mild stress.
AB  - The involvement of the beta3-adrenoceptor in the antidepressant-like effects of
      the beta3-adrenoceptor-agonist amibegron is addressed in the chronic mild stress,
      using adrenergic beta3-receptor knockout (Adrb3tm1Lowl) mice. Amibegron (3
      mg/kg/day, i.p., 33 days), attenuated the physical alteration due to the
      application of repeated stress in wild-type littermates, but not in knockout
      mice. This result suggests that the beta3-adrenoceptor plays a predominant role
      in mediating antidepressant-like actions of amibegron.

PMID- 19744529
TI  - Identification of DH IC-2 as a HIF-1 independent protein involved in the adaptive
      response to hypoxia in tumor cells: A putative role in metastasis.
AB  - The master regulator of the adaptive response to hypoxia is HIF-1. However, while
      some data show that HIF-1 can control more than 80% of the genes induced under
      hypoxia, other experiments clearly demonstrate that a part of the hypoxic
      response is independent of HIF-1. The goal of this study was to identify some of
      these HIF-1 independent factors and to investigate their functional role in the
      adaptation of tumor cells to hypoxia. We show that the cytoplasmic dynein
      intermediate chain 2 (DH IC-2), a component of an intracellular ATPase minus-end
      directed tubulin-based motile complex, was stabilized and post-translationally
      modified under hypoxia in a HIF-1 independent way. We identified this
      modification as a phosphorylation by protein kinase C, which is inhibited under
      hypoxia. In parallel, the migration of HepG2 cells was enhanced under hypoxia.
      Cell migration was also increased, to the same extent, by the invalidation of DH
      IC-2 using siRNA. Taken together, these results suggest that under hypoxia, a
      specific modification of DH IC-2 may modulate its activity, and in turn promote
      cell migration. These results are important to better understand cancer
      development since they highlight a HIF-1 independent mechanism, which may be
      involved in metastasis.

PMID- 19744530
TI  - Inhibition of TGF-beta1 promotes functional recovery after spinal cord injury.
AB  - Trauma to the spinal cord initiates a series of cellular and biochemical
      processes that damage both neurons and glia. TGF-beta and its receptors are
      expressed around the injury site following a spinal cord injury. Here, we report
      that the intrathecal administration of a neutralizing antibody to TGF-beta1 in
      rats with thoracic spinal cord contusion results in a significant enhancement of
      the locomotor recovery. The inhibition of TGF-beta1 suppresses glial scar
      formation and upregulates microglia/macrophage activation after the injury,
      presumably providing a favorable environment for restoration of the neural
      network. Rats treated with the anti-TGF-beta1 antibody exhibited a mild
      enhancement of growth and/or preservation of axons in the injured spinal cord
      caudal to the site of contusion. These results support the possibility of using
      TGF-beta1 inhibitors in the treatment of human spinal cord injuries.

PMID- 19744531
TI  - Delivery of nucleic acids with a stearylated (RxR)4 peptide using a non-covalent
      co-incubation strategy.
AB  - In recent years, oligonucleotide-based molecules have been intensely used to
      modulate gene expression. All these molecules share the common feature of being
      essentially impermeable over cellular membranes and they therefore require
      efficient delivery vectors. Cell-penetrating peptides are a group of delivery
      peptides that has been readily used for nucleic acid delivery. In particular,
      polyarginine and derivates thereof, i.e. the (RxR)(4) peptide, have been applied
      with success both in vitro and in vivo. A major problem, however, with these
      arginine-rich peptides is that they frequently remain trapped in endosomal
      compartments following internalization. The activity of polyarginine has
      previously been improved by conjugation to a stearyl moiety. Therefore, we sought
      to investigate what impact such modification would have on the pre-clinically
      used (RxR)(4) peptide for non-covalent delivery of plasmids and splice-correcting
      oligonucleotides (SCOs) and compare it with stearylated Arg9 and Lipofectamine
      2000. We show that stearyl-(RxR)(4) mediates efficient plasmid transfections in
      several cell lines and the expression levels are significantly higher than when
      using unmodified (RxR)(4) or stearylated Arg9. Although the transfection
      efficiency is lower than with Lipofectamine 2000, we show that stearyl-(RxR)(4)
      is substantially less toxic. Furthermore, using a functional splice-correction
      assay, we show that stearyl-(RxR)(4) complexed with 2'-OMe SCOs promotes
      significant splice correction whereas stearyl-Arg9 fails to do so. Moreover,
      stearyl-(RxR)(4) promotes dose-dependent splice correction in parity with
      (RxR)(4)-PMO covalent conjugates, but at least 10-times lower concentration.
      These features make this stearic acid modified analog of (RxR)(4) an intriguing
      vector for future in vivo experiments.

PMID- 19744532
TI  - Attachment and weight and shape concerns in inpatient overweight youngsters.
AB  - OBJECTIVE: The aim of this study was to investigate the associations between
      weight and shape concerns and attachment towards mother and father in inpatient
      obese youngsters. METHOD: In a sample of 39 inpatient obese youngsters weight and
      shape concerns were measured with the Children's Version of the Eating Disorder
      Examination and attachment was measured using the Relationship Questionnaire.
      RESULTS: Pearson correlation analyses demonstrated that attachment towards mother
      was linked with both weight and shape concerns, whereas attachment towards father
      was uniquely linked with weight concerns. CONCLUSION: This study demonstrated an
      association between attachment and weight and shape concerns in inpatient obese
      youngsters. This suggests that relationships with attachment figures should be
      taken into account when these youngsters require treatment for eating disorder
      symptoms.

PMID- 19744533
TI  - Visual exposure impacts on toddlers' willingness to taste fruits and vegetables.
AB  - This study explores the effects of exposure to pictures of fruits and vegetables
      on young children's willingness to taste the foods. The parents of 20 toddlers
      aged 21-24 months were asked to read a picture book about four foods with their
      child every day for two weeks. In a subsequent 'taste test' children displayed a
      neophobic pattern of behaviour towards foods to which they had not been exposed,
      but not towards exposed foods. Furthermore, while exposure served to decrease
      children's willingness to taste familiar vegetables, it increased their
      willingness to taste unfamiliar fruits.

PMID- 19744534
TI  - A new role of phosphopeptides as bioactive peptides released during milk casein
      digestion in the young mammal: regulation of gastric secretion.
AB  - The aim of this work was to study in vivo the effect of ingestion of
      phosphopeptides (PP) alone or associated with caseinomacropeptide (CMP) on
      gastric secretion and to elucidate some possible mechanisms involved. Seven
      calves fitted with a gastric pouch received either a diet based on whey proteins
      without PP and CMP (C diet) or C diet in which PP or PP+CMP was introduced at
      concentrations similar to that of PP or PP+CMP in cow milk (PP diet and PP+CMP
      diet, respectively). Gastric juice secretion was measured during successive
      periods throughout the day. Twenty-four calves were fitted with a catheter
      introduced in one external jugular vein for blood sample collections. The daily
      secretion of electrolytes decreased with the presence of PP or PP+CMP in the
      diet. During the day, peptide supplementation in the diet resulted in (1) short
      term (1st-2nd postprandial h), a decrease of secreted quantities of gastric
      juice, enzymes and electrolytes, (2) long term (7-24h after the morning meal), a
      decrease of electrolyte secretions. Intervention of gastrin, CCK, somatostatin
      and BPP could be probable. Globally, inhibition of gastric secretions seemed more
      important when PP was given in association with CMP in the diet rather than
      alone. CMP and PP may have short and long term action respectively over the 24h
      day. To our knowledge, it is the first time that phosphopeptides coming from milk
      casein digestion are demonstrated to inhibit gastric secretion. Therapeutic uses
      are suggested.

PMID- 19744535
TI  - The nitric oxide-releasing derivative of ferulic acid NCX 2057 antagonized delay
      dependent and scopolamine-induced performance deficits in a recognition memory
      task in the rat.
AB  - Nitric oxide (NO) is considered as an intracellular messenger in the brain. Its
      involvement in learning and memory processes has been proposed. The present study
      was designed to investigate the effects of the NO-releasing derivative of ferulic
      acid NCX 2057 on rats' recognition memory. For this purpose the object
      recognition task was selected. Post-training treatment with NCX 2057 (10 mg/kg,
      i.p.) and with the reference compound, the NO donor molsidomine (4 mg/kg, i.p.),
      antagonized extinction of recognition memory in the normal rat. Conversely,
      animals treated with the parent compound ferulic acid (1.9, 6.2 and 18.7 mg/kg,
      i.p.) failed to do so. In addition, NCX 2057 (3 and 10 mg/kg, i.p) reversed the
      scopolamine (0.2 mg/kg, s.c.)-induced performance deficits in this recognition
      memory task. These results indicate that this novel NO donor may modulate
      different aspects of recognition memory and suggest that an interaction between
      the nitrergic and cholinergic system is relevant to cognition.

PMID- 19744536
TI  - White matter reduction in patients with schizophrenia as revealed by voxel-based
      morphometry: an activation likelihood estimation meta-analysis.
AB  - Schizophrenia is thought to be a mental disorder caused by the disconnection of
      brain regions. Cumulative evidence of white matter deficit in patients with
      schizophrenia has been reported using voxel-based morphometry (VBM), but these
      studies have not been quantitatively reviewed. In the study reported herein, we
      used activation likelihood estimation (ALE) analysis to quantitatively estimate
      focal white matter abnormalities in patients with schizophrenia. Seventeen
      studies that compared the white matter deficit of patients with schizophrenia and
      healthy controls were ascertained. The frontal white matter regions and internal
      capsule revealed consistent white matter reduction in patient groups relative to
      healthy controls, suggesting a clear focal white matter deficit in patients with
      schizophrenia. These results support the macro-circuit theory of white matter
      change in schizophrenia.

PMID- 19744537
TI  - The effect of different surface treatments on bond strength between leucite
      reinforced feldspathic ceramic and composite resin.
AB  - OBJECTIVES: The aim of this study was to evaluate the effect of different surface
      treatments on the microtensile bond strength between a leucite reinforced glass
      ceramic and composite resin. METHODS: Leucite reinforced ceramic blocks (n=24)
      were constructed using the hot pressing technique. The blocks were assigned to 4
      groups, which received the following surface treatments: G1: hydrofluoric (HF)
      acid and silane; G2: silane alone; G3: HF acid and silane then dried with warm
      air (100 degrees C); G4: silane alone then dried with warm air (100 degrees C).
      Unfilled resin was applied, followed by composite resin. Specimens were prepared
      and loaded in tension to determine the microtensile bond strength. Failure modes
      were classified by stereo- and scanning electron microscopy (SEM). Data was
      analysed using Kruskal-Wallis test followed by the Dunn's multiple range test.
      RESULTS: The groups including the warm air step (G3 and G4) achieved a
      significantly stronger adhesion than G1 and G2. Pre-treatment of the surface with
      hydrofluoric acid in G1 resulted in significantly higher bond strength than G2.
      Failures were mostly cohesive in the luting resin for G1, G3 and G4 and mainly
      adhesive at the ceramic-resin interface in G2. CONCLUSIONS: The method of
      application of silane to the ceramic surface can have a significant influence on
      the adhesion between the ceramic restoration and the resin cement. Enhancing the
      condensation reaction by drying the silane with a 100C warm air stream
      significantly improved the microtensile bond strength, possibly eliminating the
      need for the hydrofluoric acid etching step.

PMID- 19744538
TI  - Respiratory variability preceding and following sighs: a resetter hypothesis.
AB  - Respiratory behavior is characterized by complex variability with structured and
      random components. Assuming that both a lack of variability and too much
      randomness represent suboptimal breathing regulation, we hypothesized that
      sighing acts as a resetter inducing structured variability. Spontaneous breathing
      was measured in healthy persons (N=42) during a 20min period of quiet sitting
      using the LifeShirt((r)) System. Four blocks of 10 breaths with a 50% window
      overlap were determined before and after spontaneous sighs. Total respiratory
      variability of minute ventilation was measured using the coefficient of variation
      and structured (correlated) variability was quantified using autocorrelation.
      Towards a sigh, total variability gradually increased without concomittant
      changes in correlated variability, suggesting that randomness increased. After a
      sigh, correlated variability increased. No changes in variability were found in
      comparable epochs without intermediate sighs. We conclude that a sigh resets
      structured respiratory variability, enhancing information processing in the
      respiratory system.

PMID- 19744539
TI  - Ex vivo expansion of human hematopoietic stem cells by a small-molecule agonist
      of c-MPL.
AB  - OBJECTIVE: The signaling by thrombopoietin (TPO) via its receptor, c-MPL, plays a
      crucial role in the maintenance of hematopoietic stem cells (HSCs). Small
      molecule c-MPL agonists have recently been shown to be beneficial in the
      treatment of thrombocytopenia. However, their effects on HSCs have not yet been
      explored. In this study, we evaluated the effects of NR-101, a novel small
      molecule c-MPL agonist, on the ex vivo expansion of human cord blood (hCB) HSCs.
      MATERIALS AND METHODS: hCB CD34(+) or CD34(+)CD38(-) hematopoietic stem and
      progenitor cells were cultured for 7 days in the presence of thrombopoietin (TPO)
      or NR-101, and then subjected to flow cytometric analyses, colony-forming cell
      assays, and severe combined immunodeficiency-repopulating cell assays. RESULTS:
      During a 7-day culture of CD34(+) or CD34(+)CD38(-) hematopoietic stem and
      progenitor cells, NR-101 efficiently increased their numbers, with a greater than
      twofold increase compared to TPO, although its effect on megakaryocytopoiesis was
      comparable to that of TPO. Correspondingly, severe combined immunodeficiency
      repopulating cells were increased 2.9-fold during a 7-day culture with NR-101
      compared to freshly isolated CD34(+) cells, and 2.3-fold compared to that with
      TPO. Of note, NR-101 persistently activated signal transducer and activator of
      transcription (STAT) 5 but not signal transducer and activator of transcription
      3. Furthermore, NR-101 induced a long-term accumulation of hypoxia-inducible
      factor-1alpha protein and enhanced activation of its downstream target genes.
      CONCLUSION: This is the first time that a small-molecule c-MPL agonist has been
      demonstrated to promote net expansion of HSCs. NR-101 is more efficient in ex
      vivo expansion of HSCs than TPO. NR-101 could be a useful tool for the
      therapeutic manipulation of human HSCs.

PMID- 19744540
TI  - Modeling of human P450 oxidoreductase structure by in silico mutagenesis and MD
      simulation.
AB  - P450 oxidoreductase (POR) is the obligate electron donor for microsomal
      cytochrome P450s and mutations in POR cause several metabolic disorders. We have
      modeled the structure of human P450 oxidoreductase by in silico amino acid
      replacements in the rat POR crystal structure. The rat POR has 94% homology with
      human POR and 38 amino acids were replaced to make its sequence identical to
      human POR. Several rounds of molecular dynamic simulations refined the model and
      removed structural clashes from side chain alterations of replaced amino acids.
      This approach has the advantage of keeping the cofactor contacts and structural
      features of the core enzyme intact which could not be achieved by homology based
      approaches. The final model from our approach was of high quality and compared
      well with experimentally determined structures of other PORs. This model will be
      used for analyzing the structural implications of mutations and polymorphisms in
      human POR.

PMID- 19744542
TI  - Unliganded estrogen receptor-beta regulation of genes is inhibited by tamoxifen.
AB  - Tamoxifen can stimulate the growth of some breast tumors and others can become
      resistant to tamoxifen. We previously showed that unliganded ERbeta inhibits
      ERalpha-mediated proliferation of MCF-7 cells. We investigated if tamoxifen might
      have a potential negative effect on some breast cancer cells by blocking the
      effects of unliganded ERbeta on gene regulation. Gene expression profiles
      demonstrated that unliganded ERbeta upregulated 196 genes in MCF-7 cells.
      Tamoxifen significantly inhibited 73 of these genes by greater than 30%,
      including several growth-inhibitory genes. To explore the mechanism whereby
      unliganded ERbeta activates genes and how tamoxifen blocks this effect, we used
      doxycycline-inducible U2OS-ERbeta cells to produce unliganded ERbeta. Doxycycline
      produced a dose-dependent activation of the NKG2E, MSMB and TUB3A genes, which
      was abolished by tamoxifen. Unliganded ERbeta recruitment of SRC-2 to the NKG2E
      gene was blocked by tamoxifen. Our findings suggest that tamoxifen might exert a
      negative effect on ERbeta expressing tumors due to its antagonistic action on
      unliganded ERbeta.

PMID- 19744543
TI  - In situ coexpression of glucose and monocarboxylate transporter mRNAs in
      metabolic-sensitive caudal dorsal vagal complex catecholaminergic neurons:
      transcriptional reactivity to insulin-induced hypoglycemia and caudal hindbrain
      glucose or lactate repletion during insulin-induced hypoglycemia.
AB  - The neurochemical phenotype(s) of metabolic sensing neurons in the dorsal vagal
      complex (DVC) remains unclear. These studies utilized single-cell quantitative
      real-time RT-PCR, in conjunction with laser-catapult microdissection, to address
      the hypothesis that DVC A2 neurons express genes that encode the characterized
      metabolic transducers, e.g. glucokinase (GCK) and the energy-dependent potassium
      channel, K(ATP). Studies show that either glucose or lactate alters synaptic
      firing of DVC chemosensory neurons, and that delivery of the latter fuel into the
      caudal hindbrain amplifies insulin-induced hypoglycemia (IIH) and elevates
      neuronal glucose and monocarboxylate transporter, GCK, and sulfonylurea-1 mRNA in
      the DVC. We thus examined the additional premise that IIH modifies A2 substrate
      transporter and metabolic transducer gene profiles, and that such transcriptional
      responses may be reversed by exogenous lactate and/or glucose. Individual
      tyrosine hydroxylase (TH)-immunoreactive (-ir) A2 neurons were microdissected
      from the caudal DVC 2 h after injection of insulin or saline, and continuous
      caudal fourth ventricular (CV4) infusion of lactate, glucose, or artificial
      cerebrospinal fluid. The data show that IIH decreased MCT2, but elevated GLUT3,
      GLUT4, GCK, and SUR-1 transcripts in A2 neurons. Blood glucose levels in insulin
      injected rats were further reduced by CV4 infusion of either lactate or glucose.
      Lactate plus insulin reversed hypoglycemic reductions in MCT2 mRNA and further
      augmented GLUT3 transcripts in A2 neurons, whereas glucose infusion in insulin
      injected rats further increased GLUT3 and GCK gene profiles. The present results
      demonstrate that caudal DVC A2 neurons express molecular markers for metabolic
      sensing, and genes that encode glucose and monocarboxylate transporters. Evidence
      that IIH reduces A2 MCT2, but elevates GLUT3 and GLUT4 gene profiles suggests
      that glucose may be a primary energy source to these cells during hypoglycemia,
      while decreased lactate uptake, alone or relative to glucose uptake, may be a
      critical manifestation of systemic glucose deficiency at the cellular level.
      Findings that singular fuel repletion does not normalize hypoglycemic patterns of
      glucose transporter, GCK, or SUR-1 mRNA expression in A2 neurons imply that
      sufficient supply of both energy substrates is required for metabolic balance,
      and that cellular adaptation to the prevalence of either fuel may increase
      cellular dependence on glucose-specific metabolites or other products.

PMID- 19744544
TI  - Sustained expression of interleukin-1beta in mouse hippocampus impairs spatial
      memory.
AB  - Glial activation and neuroinflammation occur in neurodegenerative disease and
      brain injury, however their presence in normal brain aging suggests that chronic
      neuroinflammation may be a factor in age-related dementia. Few studies have
      investigated the impact of sustained elevation of hippocampal interleukin-1beta,
      a pro-inflammatory cytokine upregulated during aging and Alzheimer's disease, on
      cognition in mice. We utilized the IL-1beta(XAT) transgenic mouse to initiate
      bilateral hippocampal overexpression of interleukin-1beta to determine the
      influence of sustained neuroinflammation independent of disease pathology.
      Fourteen days following transgene induction, adult male and female IL-1beta(XAT)
      mice were tested on non-spatial and spatial versions of the Morris water maze.
      For the spatial component, one retention trial was conducted 48 h after
      completion of a 3 day acquisition protocol (eight trials per day). Induction of
      IL-1beta did not impact non-spatial learning, but was associated with delayed
      acquisition and decreased retention of the spatial task. These behavioral
      impairments were accompanied by robust reactive gliosis and elevated mRNA
      expression of inflammatory genes in the hippocampus. Our results suggest that
      prolonged neuroinflammation response per se may impact mnemonic processes and
      support the future application of IL-1beta(XAT) transgenic mice to investigate
      chronic neuroinflammation in age- and pathology-related cognitive dysfunction.

PMID- 19744545
TI  - Effect of puerarin on P2X3 receptor involved in hyperalgesia after burn injury in
      the rat.
AB  - The study investigated the effects of puerarin on P2X(3) receptor involved in
      hyperalgesia after burn injury in the rat. Superficial second degree burn injury
      models were adopted. Mechanical withdrawal threshold (MWT) and thermal withdrawal
      latency (TWL) were measured and the P2X(3) receptor expressions in dorsal root
      ganglion (DRG) from burn injury models rats were detected by
      immunohistochemistry, in situ hybridization, RT-PCR and western blot. MWL and TWL
      in untreated superficial second paw burn rats were reduced. MWL and TWL of
      puerarin-treated superficial second paw burn rats showed significant increase
      compared with untreated superficial second paw burn rats. Puerarin can decrease
      the hyperalgesia after burn injury. At day 3 post-burn, the expressions of P2X(3)
      protein and mRNA in DRG neurons in untreated superficial second degree back burn
      group were increased significantly compared with sham back burn group, puerarin
      treated back unburned control group, blank back control group, while in puerarin
      treated superficial second degree back burn group, the P2X(3) protein and mRNA
      expressions were decreased markedly. There is no significant difference in sham
      back burn group, puerarin-treated back unburned control group, blank back control
      group. Therefore, puerarin may reduce the nociceptive transmission of burn injury
      pain mediated by P2X(3) receptor and alleviate P2X(3) receptor involved in
      hyperalgesia after burn injury in the rats.

PMID- 19744547
TI  - Percent body fat is related to delay and probability discounting for food in
      humans.
AB  - This study describes delay and probability discounting patterns for hypothetical
      food and money in relation to percent body fat (PBF). Sixty university students
      completed four computerized discounting tasks in which they were asked to make a
      series of hypothetical decisions between (a) 10 dollars after one of several
      different delays (1, 2, 30, 180, and 365 days) or a smaller amount of money
      available immediately; (b) 10 bites of food after one of several delays (1, 2, 5,
      10, and 20h) or a smaller number of bites available immediately; (c) $10 at one
      of several probabilities (0.9, 0.75, 0.5, 0.25, 0.1) or a smaller amount of money
      to be received for sure; and (d) 10 bites of food at one of several probabilities
      (0.9, 0.75, 0.5, 0.25, 0.1) or a smaller number of bites to be received for sure.
      Median indifference points for all participants across each task were well
      described using the hyperbolic discounting function. Results suggest that percent
      body fat predicted discounting for hypothetical food, but not money, using
      regression analyses with the entire sample and when comparing individuals in the
      high and low quartiles for PBF. None of the other dietary variables (body mass
      index, subjective hunger, and time since last meal or snack) were related to
      discounting patterns. This suggests that individuals with high PBF may exhibit
      heightened sensitivities to delay and probability when making decisions about
      food.

PMID- 19744546
TI  - Estrogen inhibits tuberoinfundibular dopaminergic neurons but does not cause
      irreversible damage.
AB  - Dopaminergic neurons of the hypothalamic tuberoinfundibular dopaminergic (TIDA)
      system exert a tonic inhibitory control on prolactin (PRL) secretion whereas
      estrogen, known to inhibit TIDA neuron function, has been postulated to be toxic
      to TIDA neurons when it is chronically high. In order to determine whether
      estrogen in high doses can cause permanent damage to TIDA function, we submitted
      young female rats to continue high doses of estrogen administered, either
      centrally (intrahypothalamic estrogen implants) or peripherally (subcutaneous
      estrogen implants or weekly intramuscular (i.m.) injections for 7 weeks),
      subsequently withdrawing the steroid and observing the evolution of lactotrophes,
      serum PRL and TIDA neurons. Serum PRL was measured by radioimmunoassay whereas
      tyrosine hydroxylase positive (TH+) neurons and PRL cells were morphometrically
      assessed in sections of fixed hypothalami and pituitaries, respectively. After 30
      days, hypothalamic estrogen implants induced a significant increase in serum PRL,
      whereas TH+ neurons were not detectable in the arcuate-periventricular
      hypothalamic (ARC) region of estrogen-implanted rats. Removal of implants on day
      30 restored TH expression in the ARC and brought serum PRL back to basal levels
      30 days after estrogen withdrawal. Subcutaneous or i.m. administration of
      estrogen for 7 weeks induced a marked hyperprolactinemia. However, 30 weeks after
      estrogen withdrawal, TH neuron numbers in the ARC were back to normal and serum
      PRL returned to basal levels. After peripheral but not central estrogen
      withdrawal, pituitary weight and lactotrophic cell numbers remained slightly
      increased. Our data suggest that estrogen even at high doses, does not cause
      permanent damage to TIDA neurons.

PMID- 19744548
TI  - Rotifer rDNA-specific R9 retrotransposable elements generate an exceptionally
      long target site duplication upon insertion.
AB  - Ribosomal DNA genes in many eukaryotes contain insertions of non-LTR
      retrotransposable elements belonging to the R2 clade. These elements persist in
      the host genomes by inserting site-specifically into multicopy target sites,
      thereby avoiding random disruption of single-copy host genes. Here we describe R9
      retrotransposons from the R2 clade in the 28S RNA genes of bdelloid rotifers,
      small freshwater invertebrate animals best known for their long-term asexuality
      and for their ability to survive repeated cycles of desiccation and rehydration.
      While the structural organization of R9 elements is highly similar to that of
      other members of the R2 clade, they are characterized by two distinct features:
      site-specific insertion into a previously unreported target sequence within the
      28S gene, and an unusually long target site duplication of 126 bp. We discuss the
      implications of these findings in the context of bdelloid genome organization and
      the mechanisms of target-primed reverse transcription.

PMID- 19744549
TI  - Fruit extracts of Momordica charantia potentiate glucose uptake and up-regulate
      Glut-4, PPAR gamma and PI3K.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Momordica charantia fruit is a widely used
      traditional medicinal herb as, anti-diabetic, anti-HIV, anti-ulcer, anti
      inflammatory, anti-leukemic, anti-microbial, and anti-tumor. AIMS OF STUDY: The
      present study is undertaken to investigate the possible mode of action of fruit
      extracts derived from Momordica charantia (MC) and study its pharmacological
      effects for controlling diabetic mellitus. Effects of aqueous and chloroform
      extracts of Momordica charantia fruit on glucose uptake and up-regulation of
      glucose transporter (Glut-4), peroxisome proliferator activator receptor gamma
      (PPAR gamma) and phosphatidylinositol-3 kinase (PI3K), were investigated to show
      its efficacy as a hypoglycaemic agent. MATERIALS AND METHODS: Dose dependent
      glucose uptake assay was performed on L6 myotubes using 2-deoxy-D-[1-(3)H]
      glucose. Up-regulatory effects of the extracts on the mRNA expression level of
      Glut-4, PPAR gamma and PI3K have been studied. RESULTS: The association of
      Momordica charantia with the aqueous and chloroform extracts of Momordica
      charantia fruit at 6 microg/ml has shown significant up-regulatory effect,
      respectively, by 3.6-, 2.8- and 3.8-fold on the battery of targets Glut-4, PPAR
      gamma and PI3K involved in glucose transport. The up-regulation of glucose uptake
      was comparable with insulin and rosiglitazone which was approximately 2-fold over
      the control. Moreover, the inhibitory effect of the cyclohexamide on Momordica
      charantia fruit extract mediated glucose uptake suggested the requirement of new
      protein synthesis for the enhanced glucose uptake. CONCLUSION: This study
      demonstrated the significance of Glut-4, PPAR gamma and PI3K up-regulation by
      Momordica charantia in augmenting the glucose uptake and homeostasis.

PMID- 19744550
TI  - Chilli peppers--a review on tissue culture and transgenesis.
AB  - Biotechnology techniques involving plant tissue culture and recombinant DNA
      technologies are powerful tools that can complement conventional breeding and
      expedite Capsicum improvement. The rate of progress in Capsicum is relatively
      slower than other members of Solanaceae because of its high genotypic dependence
      and recalcitrant nature. Capsicum is a recalcitrant plant in terms of in vitro
      cell, tissue and organ differentiation, plant regeneration and genetic
      transformation which makes it difficult to apply recombinant DNA technologies
      aimed at genetic improvement against pests, diseases and abiotic stress. Despite
      this, application of tissue culture and genetic transformation have led to
      significant development in chilli pepper plants, and studies are underway to
      achieve the targets of pre-harvest improvement and post-harvest characterization
      for value addition to this crop. This review presents a consolidated account of
      in vitro propagation and focuses upon contemporary information on
      biotechnological advances made in Capsicum.

PMID- 19744551
TI  - Early life experience alters behavioral responses to sweet food and accumbal
      dopamine metabolism.
AB  - Neonatal handling in rats persistently alters behavioral parameters and responses
      to stress. Such animals eat more sweet food in adult life, without alterations in
      lab chow ingestion. Here, we show that neonatally handled rats display greater
      incentive salience to a sweet reward in a runway test; however they are less
      prone to conditioned place preference and show less positive hedonic reactions to
      sweet food. When injected with methylphenidate (a dopamine mimetic agent), non
      handled rats increase their sweet food ingestion in the fasted state, while
      neonatally handled rats do not respond. We did not observe any differences
      regarding baseline general ambulatory activity between the groups. A lower
      dopamine metabolism in the nucleus accumbens was observed in handled animals,
      without differences in norepinephrine content. We suggest that early handling
      leads to a particular response to positive reinforcers such as palatable food, in
      a very peculiar fashion of higher ingestion but lower hedonic impact, as well as
      higher incentive salience, but diminished dopaminergic metabolism in the nucleus
      accumbens.

PMID- 19744552
TI  - Microcins and urovirulence in Escherichia coli.
AB  - Urinary tract infections are among the most common infectious diseases
      encountered in humans and Escherichia coli is their leading etiologic agent.
      Uropathogenic E. coli encompasses a group of bacteria possessing a variable
      virulence gene assortment. It is generally agreed that many urovirulence factors
      remain to be discovered and that this information is required to gain knowledge
      on the pathogenic processes underlying the different clinical presentations of
      urinary tract infections. The production of higher-molecular-mass microcins, a
      group of ribosomally-synthesized peptide antibiotics comprising microcins H47,
      I47, E492, M and ColV, has been proposed as a virulence trait of some
      uropathogenic E. coli. To study this possibility, clones producing any of these
      microcins were selected from a collection of 160 Gram-negative clinical isolates
      from urine cultures and their virulence profile was analyzed. The study consisted
      in surveying genetic loci known to be relevant to urinary tract infection caused
      by E. coli. Depending on the type of microcin produced, different virulence
      patterns were observed which seemed to be determined by the degree of
      compatibility between virulence and microcin loci. In conclusion, results pointed
      to a relationship between higher-molecular-mass microcins and urovirulence.

PMID- 19744553
TI  - Identification and characterization of inosine 5-monophosphate dehydrogenase in
      Streptococcus suis type 2.
AB  - Streptococcus suis type 2 is a swine pathogen responsible for diverse diseases.
      Although many virulent factors have been identified and studied, relatively
      little is known about the pathogenic mechanisms of type 2. The aim of the study
      was to identify and understand the characterization of Inosine 5-monophosphate
      dehydrogenase (IMPDH). A 957-bp gene, impdh, was identified in the virulent S.
      suis serotype 2 (SS2), and analysis of the predicted IMPDH sequence revealed IMP
      dehydrogenase/GMP reductase domain. The gene encoding for the IMPDH of S. suis
      was cloned and sequenced. The DNA sequence contained an open reading frame
      encoding for a 318 amino acid polypeptide exhibiting 23% sequence identity with
      the IMPDH from Streptococcus pyogenes (YP281355) and Streptococcus pneumoniae
      (ZP00404150). Using the pET(32) expression plasmid, the impdh gene was inducibly
      overexpressed in Escherichia coli to produce IMPDH with a hexahistidyl N-terminus
      to permit its purification. The (His)6 IMPDH protein was found to possess
      functional IMPDH enzymatic activity after the purification. The impdh-knockout
      SS2 mutant ( Delta IMPDH) constructed in this study was slower in growth and one
      pH unit higher than SS2-H after 6 h of culturing, and found to be attenuated in
      mouse models of infection for 2.5 times and not be capable of causing death in
      porcine models of infection in contrast with the parent SS2-H.

PMID- 19744554
TI  - Monoamine oxidase activity in placenta in relation to manganese, cadmium, lead,
      and mercury at delivery.
AB  - BACKGROUND: Environmental prenatal exposure to potentially neurotoxic metals
      poses a particular challenge with regard to the study of early toxic effects.
      Monoamine oxidase activity, shown to be influenced by metals in experimental
      studies, could be a useful biomarker in humans. OBJECTIVE: To examine the
      relationship between blood metal concentrations at delivery and placenta MAO
      activity. METHODS: The study was performed in 163 pregnancies. Maternal and cord
      blood samples were obtained for manganese (Mn), lead (Pb), and cadmium (Cd)
      determination. Mercury (Hg) was also analysed in maternal hair. Placental samples
      were stored immediately after expulsion and total MAO activity was measured.
      RESULTS: MAO activity was significantly positively correlated with maternal and
      cord blood Mn concentrations in subjects with high MAO activity. In subjects with
      low MAO activity, maternal hair Hg was negatively correlated with MAO.
      CONCLUSION: Our results suggest the use of placental MAO as a potential surrogate
      marker of Mn toxicity in the newborn and its correlation with psychomotor
      development should be further investigated.

PMID- 19744555
TI  - Sumoylation of forkhead L2 by Ubc9 is required for its activity as a
      transcriptional repressor of the Steroidogenic Acute Regulatory gene.
AB  - Forkhead L2 (FOXL2) is a member of the forkhead/hepatocyte nuclear factor 3
      (FKH/HNF3) gene family of transcription factors and acts as a transcriptional
      repressor of the Steroidogenic Acute Regulatory (StAR) gene, a marker of
      granulosa cell differentiation. FOXL2 may play a role in ovarian follicle
      maturation and prevent premature follicle depletion leading to premature ovarian
      failure. In this study, we found that FOXL2 interacts with Ubc9, an E2
      conjugating enzyme that mediates sumoylation, a key mechanism in transcriptional
      regulation. FOXL2 and Ubc9 are co-expressed in granulosa cells of small and
      medium ovarian follicles. FOXL2 is sumoylated by Ubc9, and this Ubc9-mediated
      sumoylation is essential to the transcriptional activity of FOXL2 on the StAR
      promoter. As FOXL2 is endogenous to granulosa cells, we generated a stable cell
      line expressing FOXL2 and found that activity of the StAR promoter in this cell
      line is greatly decreased in the presence of Ubc9. The sumoylation site was
      identified at lysine 25 of FOXL2. Mutation of lysine 25 to arginine leads to loss
      of transcriptional repressor activity of FOXL2. Taken together, we propose that
      Ubc9-mediated sumoylation at lysine 25 of FOXL2 is required for transcriptional
      repression of the StAR gene and may be responsible for controlling the
      development of ovarian follicles.

PMID- 19744556
TI  - Degradation of cytoplasmic substrates by FtsH, a membrane-anchored protease with
      many talents.
AB  - Control of cellular processes by regulated proteolysis is conserved among all
      organisms. FtsH, the only membrane-anchored AAA protease in bacteria, fulfills a
      variety of regulatory functions. This review focuses on soluble FtsH substrates
      in Escherichia coli and in other bacteria and outlines emerging substrate
      recognition principles.

PMID- 19744557
TI  - Failure of the feeding response to fasting in carnitine-deficient juvenile
      visceral steatosis (JVS) mice: involvement of defective acyl-ghrelin secretion
      and enhanced corticotropin-releasing factor signaling in the hypothalamus.
AB  - Carnitine-deficient juvenile visceral steatosis (JVS) mice, suffering from fatty
      acid metabolism abnormalities, have reduced locomotor activity after fasting. We
      examined whether JVS mice exhibit specific defect in the feeding response to
      fasting, a key process of anti-famine homeostatic mechanism. Carnitine-deficient
      JVS mice showed grossly defective feeding response to 24 h-fasting, with almost
      no food intake in the first 4 h, in marked contrast to control animals. JVS mice
      also showed defective acyl-ghrelin response to fasting, less suppressed leptin,
      and seemingly normal corticotropin-releasing factor (CRF) expression in the
      hypothalamus despite markedly increased plasma corticosterone. The anorectic
      response was ameliorated by intraperitoneal administration of carnitine or acyl
      ghrelin, with decreased CRF expression. Intracerebroventricular treatment of CRF
      type 2 receptor antagonist, anti-sauvagine-30, recovered the defective feeding
      response of 24 h-fasted JVS mice. The defective feeding response to fasting in
      carnitine-deficient JVS mice is due to the defective acyl-ghrelin and enhanced
      CRF signaling in the hypothalamus through fatty acid metabolism abnormalities. In
      this animal model, carnitine normalizes the feeding response through an
      inhibition of CRF.

PMID- 19744558
TI  - A comparison of different purification methods of aggrecan fragments from human
      articular cartilage and synovial fluid.
AB  - In the study of aggrecan fragmentation several methods to extract and purify
      aggrecan from cartilage and synovial fluid (SF) are used. This work compares and
      evaluates the effectiveness for purification of aggrecan of the most commonly
      used methods by the ratio of sulfated glycosaminoglycan (sGAG) to protein and by
      fragment analysis by Western blot. A novel method for purification of aggrecan
      fragments from SF by boiling (Boiled SF) is also presented. Of the sGAG extracted
      from cartilage by guanidinium, 66% was recovered by associative-dissociative
      cesium chloride density gradient centrifugation (A1D1-D3) with a 9 times higher
      ratio of sGAG to protein in the A1D1 fraction. Although less enriched in
      aggrecan, the Western blot aggrecan pattern of the guanidinium extracted sample
      resembled that of the combined patterns of the A1D1, A1D2 and A1D3 fractions. The
      recoveries of sGAG from SF purified by anion chromatography and Alcian blue
      precipitation were around 50%, while the recoveries were over 80% in the
      associative or dissociative density gradient fractions (A1 and D1) and Boiled SF.
      The purification compared to neat SF ranged from 9 times in boiled SF to 1800
      1900 times in Alcian blue and D1 samples. To obtain reliable results when
      analyzing synovial fluid aggrecan fragments by Western blot, purification was
      necessary. The immuno-pattern of anion chromatography purified SF resembled the
      patterns of A1 and D1, while the pattern of Boiled SF resembled the D1 sample.
      This work suggests that aggrecan fragments extracted from cartilage by
      guanidinium need no further purification to be analyzed by Western blot, whereas
      aggrecan fragments in SF are best analyzed in the A1 and D1 fractions or in the
      Boiled SF sample.

PMID- 19744559
TI  - GPR30 gene polymorphisms are associated with progesterone receptor status and
      histopathological characteristics of breast cancer patients.
AB  - G-protein coupled receptor GPR30 has been demonstrated to mediate estrogenic
      effects on essential features of human breast cancer cells. Polymorphisms in
      GPR30 gene might therefore affect breast cancer susceptibility or tumor
      characteristics. This is the first study examining allele and genotype
      frequencies of GPR30 single nucleotide polymorphisms (SNPs) in breast cancer
      patients. A total of 257 sporadic breast cancer cases and 247 age-matched
      controls were genotyped for three GPR30 polymorphisms by means of allele-specific
      tetra-primer PCR. Comparison of the breast cancer case and the control group with
      regard to the SNP allele, genotype and haplotype frequencies did not show
      significant differences. In contrast, the GPR30 SNPs tested were significantly
      associated with tumor size, histological grading, nodal status and progesterone
      receptor (PR) status. The A allele of SNP rs3808351 was significantly less
      frequent in patients with large or G3 tumors, T allele of SNP rs11544331 less
      frequently occurred in patients with positive nodal status, suggesting that both
      SNPs might exert protective effects regarding aggressive breast cancer entities.
      Both homozygous GG genotype of promoter SNP rs3808350 and T allele of missense
      SNP rs11544331 were inversely associated with PR-negativity, suggesting that they
      might exert protective effects regarding development of PR-negative cancer. In
      conclusion, the results of this study support the important role of GPR30 in
      breast cancer and encourage functional studies on the molecular mechanisms
      underlying the association of GPR30 polymorphisms with PR status and tumor
      growth.

PMID- 19744560
TI  - The influence of host-guest inclusion complex formation on the biotransformation
      of cortisone acetate Delta(1)-dehydrogenation.
AB  - An intensive and systematic investigation had been carried out on the Delta(1)
      dehydrogenation of cortisone acetate (CA) to prednisone acetate (PA) by
      Arthrobacter simplex TCCC 11037 in the presence of native and modified beta
      cyclodextrins (beta-CDs). The biotransformation was improved through the
      formation of the host-guest inclusion complex between CA and CDs in aqueous
      solution. The inclusion complexes of CDs with CA were investigated by means of
      phase solubility, 2D NMR spectroscopy and differential scanning calorimetry
      (DSC). The structural difference of CDs resulted in the stoichiometric
      differences between the complexes, the RM-beta-CD-CA, SBE-beta-CD-CA, HP-beta-CD
      CA complexes were 1:1 whereas beta-CD-CA gave both 1:1 and 2:1 complexes, of
      which the 2:1 complex decreased the soluble CA concentration and inhibited the
      dissociation of beta-CD-CA in aqueous solution. The increase in solubility of CA
      was in the order of RM-beta-CD>SBE-beta-CD>HP-beta-CD>beta-CD. RM-beta-CD-CA, SBE
      beta-CD-CA and HP-beta-CD-CA exhibited the higher biotransformation rate in
      comparison with native beta-CD. And the solubilization of CDs for CA in aqueous
      medium plays a key role in the biotransformation process. The article focuses on
      the various factors influencing the substrate water solubility, complex stability
      and biotransformation of CA through the addition of CDs in order to solve many
      problems associated with the process of drug delivery and biotransformation of
      different novel steroids.

PMID- 19744561
TI  - Identification and characterization of eleven glutathione S-transferase genes
      from the aquatic midge Chironomus tentans (Diptera: Chironomidae).
AB  - Eleven cDNAs encoding glutathione S-transferases (GSTs) were sequenced and
      characterized in Chironomus tentans, an ecologically important aquatic midge.
      Phylogenetic analysis revealed seven GSTs in three different cytosolic classes
      including 4 in sigma (CtGSTs1, CtGSTs2, CtGSTs3, CtGSTs4), 2 in delta (CtGSTd1,
      CtGSTd2), and 1 in omega (CtGSTo1). The remaining four GSTs (CtGSTu1, CtGSTu2,
      CtGSTu3, CtGSTu4) were unclassified due to their low relatedness to currently
      known classes of insect GSTs. Reverse-transcription (RT)-PCR analysis of the 11
      GST genes showed that CtGSTd1, CtGSTu2, CtGSTu4, CtGSTs1, CtGSTs2, CtGSTs3,
      CtGSTs4 and CtGSTo1 were expressed in all tissues examined, including salivary
      glands, hemolymph, midgut, Malpighian tubules, fatbodies and carcass, whereas
      CtGSTd2 and CtGSTu1 were expressed in a limited number of tissues. CtGSTs1 and
      CtGSTs4 appeared to be the only two genes, of which expressions can be detected
      in eggs, whereas all the 11 GST genes showed various expression patterns in the
      four larval instars. However, expressions of CtGSTd2, CtGSTu1 and CtGSTu2 were
      not detectable in pupal and adult stages. Real-time quantitative PCR confirmed
      that the herbicide alachlor increased CtGSTd1, CtGSTs2 and CtGSTs3 gene
      expression by 2.1-, 2.8- and 4.3-fold, respectively, when fourth-instar midges
      were exposed to alachlor at 1000 microg/L for 72 h. Such increased gene
      expressions were associated with 2.2- and 1.8-fold decreases of total GST
      activities in vivo when CDNB and DCNB were used as substrates, respectively.
      Further studies showed that 65.5 and 73.5% of GST activities were inhibited in
      vitro by alachlor at 100 and 1000 microg/L, respectively. Because alachlor has
      been known as an electrophilic substrate that can be conjugated by glutathione
      (GSH), rapid in vitro inhibition of GST activities by alachlor suggested that
      decreased GST activities were likely caused by the depletion of GSH. However,
      alachlor may regulate different GST genes, as found in other organisms, leading
      to significantly increased transcriptional levels of CtGSTd1, CtGSTs2 and CtGSTs3
      in out of 11 GST genes examined in this study.

PMID- 19744562
TI  - Neurogenic contraction of mouse rectum via the cyclooxygenase pathway: Changes of
      PGE2-induced contraction with dextran sulfate sodium-induced colitis.
AB  - Recent reports suggest that cyclooxygenases (COXs) including COX-2 are
      constitutively expressed, and prostaglandins (PGs) regulate motility and/or
      contraction in the colon and rectum. This study examines the role of COXs in the
      regulation of neuromuscular function in longitudinal preparations of isolated
      rectum and distal colon (Side A, close to the transverse colon; and Side B, close
      to the rectum) in normal mice and after the induction of colitis by dextran
      sulfate sodium (DSS). In control rectum, electrical stimulation (ES)-induced
      contractions were inhibited by atropine and by COX inhibitors, in an independent
      manner. PGE(2) at 3microM caused a marked contraction, but the secondary response
      at 20min after the first application was 60% desensitized. In rectum from DSS
      treated mice, spontaneous and ES-induced contractions were significantly less
      intense than in the control preparations, and the response to PGE(2) was
      abolished but that to 3microM acetylcholine was not. In control distal colon, the
      responses to PGE(2) in neither side were desensitized by the repeated
      application. In DSS-treated distal colon, PGE(2) response was impaired in the two
      regions, and was desensitized on Side B more than Side A. DSS treatment impaired
      contractions by 40mM KCl in rectum and on Side B but not Side A. DSS treatment
      increased COX-2 expression in rectum, but not in distal colon. These findings
      suggest that the induction of colitis by DSS affects ES- and PGE(2)-regulated
      motility in the order rectum>distal colon close to the rectum>distal colon in
      mice.

PMID- 19744563
TI  - Cloning and expression analysis of Atlantic halibut (Hippoglossus hippoglossus)
      CD3 genes.
AB  - The CD3 complex is in higher vertebrates shown to be important for the activation
      of T-cells. The T-cell system in fish is believed to be similar to that in higher
      vertebrates, and the CD3 chains could therefore be an important marker for
      identification of T-cells in fish. Here, we report the cDNA and corresponding
      gene sequence of Atlantic halibut (Hippoglossus hippoglossus) CD3gammadelta,
      CD3varepsilon, and CD3zeta chains, and the tissue-specific expression pattern of
      CD3 and T- cell receptor (TCR) genes. Important structural characteristics
      defining the CD3 genes seemed to be conserved in the halibut CD3 chains, such as
      a signal peptide, an extracellular region, a transmembrane helix having a
      negatively charged residue, and an ITAM bearing cytoplasmic tail. The
      extracellular domain of halibut CD3gammadelta and CD3varepsilon included two
      cysteines presumably involved in Ig-fold stabilisation and the CxxCxE motif
      important for dimerization. A spliced variant of CD3varepsilon was identified,
      lacking the Ig-fold, but with the CxxCxE motif intact. The real time RT-PCR
      analysis revealed a highly similar expression pattern of the CD3 genes and the
      TCRalpha and TCRbeta genes, indicating that the functional relationship between
      the TCR and the CD3 genes are preserved in teleosts.

PMID- 19744564
TI  - FLAIR signal and texture analysis for lateralizing mesial temporal lobe epilepsy.
AB  - Standard magnetic resonance (MR) imaging analysis in several cases of mesial
      temporal lobe epilepsy (mTLE) either fail to show an identifiable hippocampal
      asymmetry or provide only subtle distinguishing features that remain
      inconclusive. A retrospective analysis of hippocampal fluid-attenuated inversion
      recovery (FLAIR) MR images was performed in cases of mTLE addressing,
      particularly, the mean and standard deviation of the signal and its texture.
      Preoperative T1-weighted and FLAIR MR images of 25 nonepileptic control subjects
      and 36 mTLE patients with Engel class Ia outcomes were analyzed. Patients
      requiring extraoperative electrocorticography (ECoG) with intracranial electrodes
      and thus judged to be more challenging were studied as a separate cohort.
      Hippocampi were manually segmented on T1-weighted images and their outlines were
      transposed onto FLAIR studies using an affine registration. Image intensity
      features including mean and standard deviation and wavelet-based texture features
      were determined for the hippocampal body. The right/left ratios of these features
      were used with a linear classifier to establish laterality. Whole hippocampal
      within-subject volume ratios were assessed for comparison. Mean and standard
      deviation of FLAIR signal intensities lateralized the site of epileptogenicity in
      98% of all cases, whereas analysis of wavelet texture features and hippocampal
      volumetry each yielded correct lateralization in 94% and 83% of cases,
      respectively. Of patients requiring more intensive study with extraoperative
      ECoG, 17/18 were lateralized effectively by the combination of mean and standard
      deviation ratios despite a ratio of mean signal intensity near one in some. The
      analysis of mean and standard deviation of FLAIR signal intensities provides a
      highly sensitive method for lateralizing the epileptic focus in mTLE over that of
      volumetry or texture analysis of the hippocampal body.

PMID- 19744565
TI  - Identifying objects impairs knowledge of other objects: a relearning explanation
      for the neural repetition effect.
AB  - Different items in long-term knowledge are stored in the neocortex as partially
      overlapping representations that can be altered slightly with usage. This
      encoding scheme affords well-documented benefits, but potential costs have not
      been well explored. Here we use functional magnetic resonance imaging (fMRI),
      neurocomputational modeling, and electrophysiological measures to show that
      strengthening some visual object representations not only enhances the subsequent
      ability to identify those (repeated) objects-an effect long known as repetition
      priming-but also impairs the ability to identify other (non-repeated) objects-a
      new effect labeled antipriming. As a result, the non-repeated objects elicit
      increased neural activity likely for the purpose of reestablishing their
      previously weakened representations. These results suggest a novel reevaluation
      of the ubiquitously observed repetition effect on neural activity, and they
      indicate that maintenance relearning may be a crucial aspect of preserving
      overlapping neural representations of visual objects in long-term memory.

PMID- 19744566
TI  - A common functional brain network for autobiographical, episodic, and semantic
      memory retrieval.
AB  - The objective of this study was to delineate a common functional network that
      underlies autobiographical, episodic, and semantic memory retrieval. We conducted
      an event-related fMRI study in which we utilized the same pictorial stimuli, but
      manipulated retrieval demands to extract autobiographical, episodic, or semantic
      memories. To assess this common network, we first examined the functional
      connectivity of regions identified by a previous analysis of task-related
      activity that were active across all three tasks. Three of these regions (left
      hippocampus, left lingual gyrus, and right caudate nucleus) appeared to share a
      common pattern of connectivity. This was confirmed in a subsequent functional
      connectivity analysis using these three regions as seeds. The results of this
      analysis showed that there was a pattern of functional connectivity that
      characterized all three seeds and that was common across the three retrieval
      conditions. Activity in inferior frontal and middle temporal cortex bilaterally,
      left temporoparietal junction, and anterior and posterior cingulate gyri was
      positively correlated with the seeds, whereas activity in posterior occipito
      temporo-parietal regions was negatively correlated. These findings support the
      idea that a common neural network underlies the retrieval of declarative memories
      regardless of memory content. This proposed network consists of increased
      activity in regions that represent internal processes of memory retrieval and
      decreased activity in regions that mediate attention to external stimuli.

PMID- 19744567
TI  - Reliability of fiber tracking measurements in diffusion tensor imaging for
      longitudinal study.
AB  - The statistical reliability of diffusion property measurements was evaluated in
      ten healthy subjects using deterministic fiber tracking to localize tracts
      affected in motor neuron disease: corticospinal tract (CST), uncinate fasciculus
      (UNC), and the corpus callosum in its entirety (CC), and its genu (GE), motor
      (CCM), and splenium (SP) fibers separately. Measurements of fractional anisotropy
      (FA), mean diffusivity (MD), axial diffusivity (lambda(1)), transverse
      diffusivity (lambda( perpendicular)), and volume of voxels containing fibers (VV)
      were obtained within each tract. To assess intra-rater and inter-rater
      reliability, two raters carried out fiber tracking five times on each scan. Scan
      rescan and longitudinal reliability were assessed in a subset of four subjects
      who had six scans, with two sets of three scans separated by 1 year. The
      statistical reliability of repeated measurements was evaluated using intraclass
      correlation coefficients (ICC) and coefficients of variation (CV). Spatial
      agreement of tract shape was assessed using the kappa (kappa) statistic. RESULTS:
      Repeated same-scan fiber tracking evaluations showed good geometric alignment
      (intra-rater kappa >0.90, inter-rater kappa >0.76) and reliable diffusion
      property measurements (intra-rater ICC >0.92, inter-rater ICC >0.77). FA, MD, and
      lambda( perpendicular) were highly reliable with repeated scans on different
      days, up to a year apart (ICC >0.8). VV also exhibited good reliability, but with
      higher CVs. We were unable to demonstrate reproducibility of lambda(1).
      Longitudinal reliability after one year was improved by averaging measurements
      from multiple scans at each time point. Fiber tracking provides a reliable tool
      for the longitudinal evaluation of white matter diffusion properties.

PMID- 19744568
TI  - Combining shape and connectivity analysis: an MRI study of thalamic degeneration
      in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is associated with neuronal loss not only in the
      hippocampus and amygdala but also in the thalamus. Anterodorsal, centromedial,
      and pulvinar nuclei are the main sites of degeneration in AD. Here we combined
      shape analysis and diffusion tensor imaging (DTI) tractography to study
      degeneration in AD in the thalamus and its connections. Structural and diffusion
      tensor MRI scans were obtained from 16 AD patients and 22 demographically similar
      healthy volunteers. The thalamus, hippocampus, and amygdala were automatically
      segmented using our locally developed algorithm, and group comparisons were
      carried out for each surface vertex. We also employed probabilistic diffusion
      tractography to obtain connectivity measures between individual thalamic voxels
      and hippocampus/amygdala voxels and to segment the internal medullary lamina
      (IML). Shape analysis showed significant bilateral regional atrophy in the dorsal
      medial part of the thalamus in AD patients compared to controls. Probabilistic
      tractography demonstrated that these regions are mainly connected with the
      hippocampus, temporal, and prefrontal cortex. Intrathalamic FA comparisons showed
      reductions in the anterodorsal region of thalamus. Intrathalamic tractography
      from this region revealed that the IML was significantly smaller in AD patients
      than in controls. We suggest that these changes can be attributed to the
      degeneration of the anterodorsal and intralaminar nuclei, respectively. In
      addition, based on previous neuropathological reports, ventral and dorsal-medial
      shape change in the thalamus in AD patients is likely to be driven by IML
      atrophy. This combined shape and connectivity analysis provides MRI evidence of
      regional thalamic degeneration in AD.

PMID- 19744569
TI  - Low nonrelapse mortality and prolonged long-term survival after reduced-intensity
      allogeneic stem cell transplantation for relapsed or refractory diffuse large B
      cell lymphoma: report of the Societe Francaise de Greffe de Moelle et de Therapie
      Cellulaire.
AB  - Patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) have a
      very poor prognosis. However, they may achieve long-term survival by undergoing
      allogeneic stem cell transplantation (SCT). The purpose of this study was to
      assess the outcome of all adult patients with DLBCL whose treatment included a
      reduced-intensity conditioning (RIC) regimen for allogeneic SCT and whose data
      were reported in the French Society of Marrow Transplantation and Cellular
      Therapy registry. Sixty-eight patients (median age: 48 years) were transplanted
      from October 1998 to January 2007. They had received a median of 2 regimens of
      therapy prior to allogeneic SCT, and 54 (79%) had already undergone SCT. Prior to
      transplantation, 32 patients (47%) were in complete remission (CR). For all
      patients but 1, conditioning regimens were based on fludarabine (Flu), which was
      combined with other chemotherapy drugs in 50 cases (74%) and with total body
      irradiation (TBI) in 17 (25%). For 56 patients (82%), the donor was an HLA
      matched sibling, and peripheral blood was the most widely used source of stem
      cells (57 patients, 84%). With a median follow-up of 49 months, estimated 2-year
      overall survival (OS), progression-free survival (PFS), and the cumulative
      incidence of relapse were 49%, 44%, and 41%, respectively. The 1-year cumulative
      incidence of nonrelapse mortality (NRM) was 23%. According to multivariate
      analysis, the patients in CR before transplantation had a significantly longer
      PFS and a lower CI of relapse than patients transplanted during partial remission
      or stable or progressive disease. These results suggest that reduced-intensity
      allergenic transplantation is an attractive therapeutic option for patients with
      high-risk DLBCL.

PMID- 19744570
TI  - Cord blood transplantation from unrelated donors in adults with high-risk acute
      myeloid leukemia.
AB  - Clinical studies focused on disease-specific outcomes of cord blood transplant
      (CBT) from unrelated donors are limited. We analyzed the outcome and prognostic
      factors of 49 adults with high-risk acute myelogenous leukemia (AML) receiving
      single-unit CBT from unrelated donors after myeloablative (MA) conditioning at a
      single institution. Conditioning regimens were based on the combination of
      thiotepa, busulfan (Bu), cyclophospamide (Cy), or fludarabine (Flu), and
      antithymocyte globulin (ATG). Cumulative incidence of myeloid and platelet
      engraftment was 96% and 73% at a median time of 20 and 62 days, respectively.
      Engraftment was significantly faster for patients receiving higher doses of
      CD34(+) cells. Confidence Interval of graft-versus-host disease (GVHD), acute
      GVHD (aGVHD) grade II-IV, III-IV, and extensive chronic GVHD (cGVHD) were 26%,
      15%, and 30%, respectively. Leukemia-free survival (LFS), nonrelapse mortality
      (NRM), and relapse at 2 years were 42%, 39%, and 19%, respectively. Low number of
      total nucleated cells (TNC) had a negative impact on NRM and LFS. Patients
      transplanted in first complete remission (CR1) receiving TNC above 2 x 10(7)/kg
      had a 4-year LFS of 75%. These results show that CBT from unrelated donors is a
      curative treatment for a substantial number of patients with high-risk AML,
      particularly if transplant is performed with highly cellular units in patients in
      first CR.

PMID- 19744571
TI  - Current status and perspectives of tyrosine kinase inhibitor treatment in the
      posttransplant period in patients with chronic myelogenous leukemia (CML).
AB  - Following the introduction of tyrosine kinase inhibitors (TKIs) in chronic
      myelogenous leukemia (CML), allogeneic stem cell transplantation (SCT) took a
      shift toward high-risk patients. Considering the high relapse rates
      posttransplant in these selected patients, several studies evaluated
      posttransplant use of the TKI imatinib. Although the number of studies are still
      limited, and data have to be confirmed by additional studies, safety of imatinib
      even within the first months after SCT seems to be acceptable. Imatinib was shown
      to be effective in patients with molecular or hematologic relapse of chronic or
      accelerated phase posttransplant (CP, AP), whereas outcomes in blast phase were
      more unfavorable. The compound further seemed beneficial for prophylactic use in
      patients who achieved complete remission posttransplant. The combination of
      imatinib with donor lymphocytes did not result in increased toxicity or graft
      versus-host disease (GVHD). First studies suggest that second-generation TKIs
      such as dasatinib or nilotinib are manageable posttransplant with acceptable
      toxicity as well. In conclusion, TKIs of the first- and second-generation are
      promising options for the posttransplant period of patients with CML, but
      algorithms for dosage, intervals from SCT, duration of application, and the
      combination with donor lymphocytes still have to be developed.

PMID- 19744572
TI  - Antiviral responses following L-leucyl-L-leucine methyl esther (LLME)-treated
      lymphocyte infusions: graft-versus-infection without graft-versus-host disease.
AB  - Although allogeneic hematopoietic progenitor cell transplant (HPCT) is curative
      therapy for many disorders, it is associated with significant morbidity and
      mortality, which can be related to graft-versus-host disease (GVHD) and the
      immunosuppressive measures required for its prevention and/or treatment. Whether
      the immunosuppression is pharmacologic or secondary to graft manipulation, the
      graft recipient is left at increased risk of the threatening opportunistic
      infection. Refractory viral diseases in the immunocompromised host have been
      treated by infusion of virus-specific lymphotyces and by unmanipulated donor
      lymphocyte infusion (DLI) therapy. L-leucyl-L-leucine methyl ester (LLME) is a
      compound that induces programmed cell death of natural killer (NK) cells,
      monocytes, granulocytes, most CD8(+) T cells, and a small fraction of CD4(+) T
      cells. We have undertaken a study of the use of LLME-treated DLI following T cell
      depleted allogeneic HPCT, specifically to aid with immune reconstitution. In this
      ongoing clinical trial, we have demonstrated the rapid emergence of virus
      specific responses following LLME DLI with minimal associated GVHD. This paper
      examines the pace of immune recovery and the rapid development of antiviral
      responses in 6 patients who developed viral infections during the time period
      immediately preceding or coincident with the administration of the LLME DLI.

PMID- 19744573
TI  - Conserved responses to trichostatin A in rodent lungs exposed to endotoxin or
      stretch.
AB  - Histone deacetylase (HDAC) isoenzymes have been suggested as possible drug
      targets in pulmonary cancer and in inflammatory lung diseases such as asthma and
      COPD. Whether HDAC inhibition is pro- or anti-inflammatory is under debate. To
      further examine this clinically relevant paradigm, we analyzed 8 genes that are
      upregulated by two pro-inflammatory stimuli, i.e. endotoxin and mechanical stress
      (overventilation), in isolated rat and mouse lungs, respectively. We studied the
      effect of the HDAC inhibitor trichostatin A (TSA) under control conditions, in
      response to endotoxin and overventilation, and on the effects of the steroid
      dexamethasone. TSA affected gene expression largely independent of the stimulus
      (endotoxin, overventilation) and the species (rat, mouse) leading to upregulation
      of some genes (Tnf, Cxcl2) and downregulation of others (Cxcl10, Timp1, Selp,
      Il6). At the protein level, TSA reduced the stimulated release of TNF, MIP-2alpha
      and IL-6, indicating that TSA may affect protein translation independent from
      gene transcription. In general, the anti-inflammatory effects of TSA on gene
      expression and protein release were additive to that of dexamethasone, suggesting
      that both drugs employ different mechanisms. We conclude that pro-inflammatory
      stimuli induce distinct sets of genes that are regulated by HDAC in a diverse,
      but consistent manner across two rodent species. The present findings together
      with previous in vivo studies suggest that the effect of HDAC inhibition in the
      intact lung is in part anti-inflammatory.

PMID- 19744574
TI  - WITHDRAWN: Fasting suppresses T cell-mediated immunity in female Mongolian
      gerbils (Meriones unguiculatus).
AB  - The Publisher regrets that this article is an accidental duplication of an
      article that has already been published, doi: 10.1016/j.cbpa.2009.09.003. The
      duplicate article has therefore been withdrawn.

PMID- 19744575
TI  - Bone morphogenetic protein 2 enhances PGE(2)-stimulated osteoclast formation in
      murine bone marrow cultures.
AB  - Bone morphogenetic protein 2 (BMP-2) is used clinically to stimulate bone
      formation and accelerate fracture repair. Adding prostaglandin (PG) E(2) or
      PGE(2) receptor agonists to BMP-2 has been proposed to improve BMP-2 efficacy.
      However, this may enhance bone resorption, since PGE(2) can increase receptor
      activator of NF-kappaB ligand (RANKL) expression and decrease osteoprotegerin
      (OPG) expression in osteoblasts, and the RANKL:OPG ratio is critical for
      osteoclast formation. We used bone marrow (BM) cultures and BM macrophage (BMM)
      cultures from outbred CD1 mice to examine effects on osteoclast formation of BMP
      2 and PGE(2). In BM cultures, which contain both osteoblastic and osteoclastic
      lineage cells, BMP-2 (100 ng/ml) alone did not increase osteoclast formation but
      enhanced the peak response to PGE(2) by 1.6-9.6-fold. In BMM cultures, which must
      be treated with RANKL because they do not contain osteoblastic cells, BMP-2 did
      not increase osteoclast formation, with or without PGE(2). Our results suggest
      that BMP-2 can increase osteoclast formation in response to PGE(2) by increasing
      the RANKL:OPG ratio in osteoblasts, which may have therapeutic implications for
      the use of BMP-2.

PMID- 19744576
TI  - Genomic organization and promoter analysis of the Trichomonas vaginalis core
      histone gene families.
AB  - Core histone gene is a well-established model to study eukaryote gene
      transcription regulation mechanism. However, the protozoan core histone gene
      regulation mechanism remains largely unknown. In this study, we observed almost
      all protozoan Trichomonas vaginalis core histone genes (60/74) organize as gene
      pairs in a head-to-head manner, thus facilitating the divergent transcription of
      both partners. Additionally, the majority of both T. vaginalis core histone genes
      pairs (50/60) and solitary genes (10/14), contain three over-represented motifs
      with conserved positional architecture at their promoter regions. Notably of the
      three motifs, Motif I is highly similar to the Inr which mediates the
      transcription start site selection in T. vaginalis. Motif II and Motif III
      preferably locate at the promoter regions of the T. vaginalis genome. Those
      findings reveal that both genomic organization and cis-acting transcription
      elements facilitate these large number of T. vaginalis core histone genes under
      the control of the same transcription machine.

PMID- 19744577
TI  - Expression profiles of seven glutathione S-transferase (GST) genes in cadmium
      exposed river pufferfish (Takifugu obscurus).
AB  - Glutathione S-transferase (GST; EC 2.5.1.18) plays a critical role in
      detoxification pathways. In this study, we report cloning and expression of seven
      genes of the GST family of the pufferfish Takifugu obscurus together with mRNA
      tissue distribution pattern and time-course of expression in response to exposure
      to cadmium. At basal levels of tissue expression, GST-Mu is highly expressed in
      liver compared with other tissues. When fish were exposed to cadmium (5 mg/L for
      96 h), expression of GST-MAPEG, GST-Mu, GST-Omega, and GST-Zeta was greatly
      increased, whereas GST-Alpha and GST-Kappa genes showed no significant response.
      These findings suggest that gene expression of a number of GST isoforms in T.
      obscurus is modulated in response to exposure to cadmium. We propose GST-Mu, GST
      Theta, and GST-Zeta as candidate biomarkers for heavy metal exposure in this
      fish.

PMID- 19744578
TI  - Yes, simultaneous damage to both the pancreas and liver are associated in
      subjects who drink excessive amounts of alcohol!

PMID- 19744579
TI  - S-Methadone augments R-methadone induced respiratory depression in the neonatal
      guinea pig.
AB  - Methadone is administered as a racemic mixture, although its analgesic and
      respiratory effects are attributed to R-isomer activity at the mu opioid receptor
      (MOP). Recently, we observed a four-fold increase in inspiratory time in 3-day
      old guinea pigs following an injection of racemic methadone. We hypothesized that
      this effect was due to augmentation of R-methadone induced respiratory depression
      by the S-methadone isomer. In the current longitudinal study, we injected 3-, 7-,
      and 14-day-old neonatal guinea pigs with saline, R-methadone, S-methadone, or R-
      plus S-methadone in order to characterize the roles of the individual isomers, as
      well as the synergistic effects of co-administration. Using plethysmography, we
      measured respiratory parameters while breathing room air and during a 5% CO(2)
      challenge. S-Methadone alone had no respiratory effects. However, the R- plus S
      methadone group showed greater respiratory depression and increased inspiratory
      time than the R-methadone group in the youngest animals, suggesting that the
      respiratory effects of R-methadone are augmented by S-methadone in early
      development.

PMID- 19744581
TI  - An observational study of timing versus appropriateness of acute plastic surgery
      referrals in the UK.
AB  - AIM: A commitment made by the UK government that all patients presenting to
      Accident and Emergency (A&E) should be treated within 4h of arrival has
      challenged both A&E departments and those to whom they refer. It has been
      suggested on one hand that referrals from A&E are not always seen promptly enough
      to meet waiting time targets, and on the other hand that referrals are sometimes
      made to help busy A&Es clear their waiting rooms rather than through clinical
      need. METHODS: To investigate these claims 'Referral Time' (the time between a
      patient arriving at A&E and being referred to Plastic Surgery), 'Review Time'
      (the time taken from referral to review by the Plastic Surgery Senior House
      Officer) and their relationship with referral appropriateness were prospectively
      examined in a UK teaching hospital. RESULTS: The mean Referral Time was 84 min
      (SD=57.3) and Review Time was 33 min (SD=27.4). Review Time did not vary
      significantly between 'appropriate' and 'inappropriate' referrals (31.3 vs 36.1
      min, p=0.357) but Referral Time was significantly quicker for 'inappropriate'
      than 'appropriate' referrals (92.8 vs 62.7 min, p=0.028). CONCLUSION: This data
      suggests that Review Time did not significantly contribute to the risk of
      patients breaching the A&E waiting time target in this study, but a correlation
      between reduced Referral Time and decreased referral appropriateness is
      consistent with referrals sometimes being made for non-clinical reasons. It is
      felt that such tactics are an inevitable consequence of an unachievable target
      placed on A&E departments and that this target should be reconsidered.

PMID- 19744580
TI  - Neuromuscular adaptations to respiratory muscle inactivity.
AB  - Cervical spinal cord injury results in significant functional impairment. It is
      important to understand the neuroplasticity in response to inactivity of
      respiratory muscles in order to prevent any associated effects that limit
      functional recovery. Recent studies have examined the mechanisms involved in
      inactivity-induced neuroplasticity of diaphragm motor units. Both spinal
      hemisection at C2 (C2HS) and tetrodotoxin (TTX)-induced phrenic nerve blockade
      result in diaphragm paralysis and inactivity of axon terminals. However, phrenic
      motoneurons are inactive with C2HS but remain active after TTX. Diaphragm muscle
      fibers ipsilateral to C2HS display minimal changes post-injury. Neuromuscular
      transmission is enhanced following C2HS but impaired following TTX. Synaptic
      vesicle pool size at diaphragm neuromuscular junctions increases after C2HS, but
      decreases after TTX. Thus, inactivity-induced neuromuscular plasticity reflects
      specific adaptations that depend on inactivity at the motoneuron rather than at
      axon terminals or muscle fibers. These results indicate that neuromuscular
      transmission and functional properties of diaphragm fibers can be maintained
      after spinal cord injury, providing a substrate for functional recovery and/or
      specific therapeutic approaches such as phrenic pacing.

PMID- 19744582
TI  - Thrombospondin-2 regulates matrix mineralization in MC3T3-E1 pre-osteoblasts.
AB  - The matricellular protein thrombospondin-2 (TSP2) has context-dependent effects
      on osteoblast lineage proliferation and differentiation. Mice lacking TSP2
      display increased endocortical bone thickness, which is associated with increased
      marrow stromal cell (MSC) number and in vitro proliferation. TSP2-null MSC also
      exhibit delayed osteoblastogenesis and enhanced adipogenesis compared to cells
      harvested from wild type mice. The goal of the present work was to more precisely
      characterize the contribution that TSP2 makes to the maturation of osteoblast
      derived extracellular matrix (ECM) using a highly characterized pre-osteoblast
      cell line. Specifically, we asked whether TSP2 influences mineralization
      indirectly through its known effects on proliferation, or whether TSP2 directly
      promotes osteoblast differentiation. To pursue these questions, we used RNA
      interference (RNAi) to inhibit TSP2 gene expression in MC3T3-E1 pre-osteoblasts.
      Introduction of siRNA oligonucleotides resulted in reduced TSP2 mRNA expression
      as early as 24 h post-transfection, and TSP2 mRNA levels remained low for 10
      days. Similarly, TSP2 protein levels in both conditioned medium and the cell
      matrix layer were reduced at 24 h post-transfection and remained reduced for 7
      days. At day 21, mineralization was significantly reduced in cells transfected
      with TSP2 siRNA when compared to cells treated with scrambled siRNA. This
      decrease in mineralization occurred without a concomitant change in cell number.
      Twenty-four hours after transfection, runx2 gene expression was transiently
      enhanced in TSP2 siRNA-treated cultures. Between 6 and 14 days post-transfection,
      runx2, osterix, alkaline phosphatase, type I collagen, osteocalcin and bone
      sialoprotein all displayed moderate increases in gene expression with TSP2 RNAi.
      As well, soluble osteocalcin levels were markedly higher in the conditioned
      medium of cells treated with TSP2 siRNA than in control siRNA-treated cells.
      Increased soluble osteocalcin occurred without a concomitant change in the levels
      of osteocalcin in the cell-ECM layer. TSP2 reduction also elicited a transient
      change in the distribution of collagen between the acid soluble cell-ECM protein
      fraction and the insoluble matrix. Together, our data suggest that TSP2 may
      promote mineralization, by facilitating proper organization of the osteoblast
      derived ECM.

PMID- 19744583
TI  - Conclusions on (cost-)effectiveness of pertussis booster vaccination strategies
      highly dependent on selections made in evidence review.
AB  - This letter reacts on a paper recently published in this journal, reviewing the
      effectiveness and (cost-)effectiveness of pertussis booster vaccination
      strategies. We argue that a different selection of (cost-)effectiveness data
      could validly be made than the one presented in the review as being considered
      most robust. In particular, we explicitly present an alternative set of (cost
      )effectiveness data.

PMID- 19744584
TI  - Narrowed TCR diversity for immunised mice challenged with recombinant influenza A
      HIV Env(311-320) virus.
AB  - Understanding CD8+ T cell responses generated by live virus vectors is critical
      for the rational design of next generation HIV CTL-based vaccines. We used
      recombinant influenza viruses expressing the HIV Env(311-320) peptide in the
      neuraminidase stalk to study response magnitude, cytokine production and
      repertoire diversity for the elicited CD8+ D(d)Env(311) CTL set. The insertion of
      the CD8+ D(d)Env(311) epitope into the NA stalk resulted in a decrease in viral
      fitness that was reflected in lower lung viral titres. While not affecting the
      magnitude of endogenous primary influenza-specific responses, the introduction of
      the D(d)Env(311) CD8+ T cell epitope altered the hierarchy of responses following
      secondary challenge. The CD8+ K(d)NP(147) response increased 9-fold in the spleen
      following secondary infection whereas the CD8+ D(d)Env(311) response increased 15
      fold in the spleen. Moreover, this study is the first to describe narrowing of
      CD8+ TCR repertoire diversity in the context of an evolving secondary immune
      response against influenza A virus. Analysis of Vbeta bias for CD8+ D(d)Env(311)
      T cell responses showed a narrowing of CD8+ Vbeta8.1/8.2 D(d)Env(311) TCR
      repertoire diversity. This work further emphasizes the importance of
      understanding vaccine-induced CD8+ T cell responses.

PMID- 19744585
TI  - HIV-1 Tat-specific IgG antibodies in high-responders target a B-cell epitope in
      the cysteine-rich domain and block extracellular Tat efficiently.
AB  - Tat, an important regulatory protein of HIV-1, has been implicated in HIV-related
      pathogenesis. Immune responses to Tat, although underrepresented, confer
      protection against disease progression, in natural infection and experimental
      immunization, making Tat an attractive vaccine candidate. Information on immune
      responses to Tat from India which has the second largest HIV incidence has been
      lacking. Here we report a cross-sectional study evaluating the humoral response
      to Tat from a large number of samples from two southern states of India. 14% of
      the seropositive (63/447) and 4.6% of seronegative samples (7/150) harbored Tat
      reactive antibodies. A significant number of the seropositive samples contained
      high levels of anti-Tat antibodies (31/447) which demonstrated class-switch to
      IgG1 and bound to Tat with high avidity. Cross-reactivity analysis showed that
      these antibodies interacted with Tat from different clades with variable degree
      with the highest interaction with subtype-AE and the least with subtype-B Tat.
      Importantly, a B-cell epitope in the cysteine-rich domain was found to be the
      most immunodominant one and antibodies interacting with this epitope blocked
      extracellular Tat efficiently. To the best of our knowledge this is the first
      report on immune responses to Tat from Indian populations and the data presented
      here could significantly contribute to HIV Tat vaccine design.

PMID- 19744586
TI  - Immunization of young African green monkeys with OprF epitope 8-OprI-type A- and
      B-flagellin fusion proteins promotes the production of protective antibodies
      against nonmucoid Pseudomonas aeruginosa.
AB  - There is currently no approved vaccine against Pseudomonas aeruginosa, the major
      cause of morbidity and mortality in cystic fibrosis (CF) patients and a major
      pathogen in ventilated and burn patients. In a previous study, we demonstrated
      the immunization of mice with OprF(311-341)-OprI-type A- and B-flagellin fusion
      proteins dramatically enhanced clearance of nonmucoid P. aeruginosa. The goal of
      the current study was to evaluate the ability of OprF(311-341)-OprI-flagellins to
      elicit the production of protective IgG in young (4-6 months old) African green
      monkeys. Intramuscular immunization of African green monkeys with 1, 3, 10, or
      30mug of OprF(311-341)-OprI-flagellins generated robust antigen-specific IgG
      responses. In addition, immunization with OprF(311-341)-OprI-flagellins elicited
      high-affinity anti-flagellins, OprI, and OprF IgG that individually promoted
      extensive deposition of complement component C3 on P. aeruginosa and synergized
      to facilitate maximal C3 deposition. Passive immunization of mice with plasma
      from OprF(311-341)-OprI-flagellins immunized monkeys significantly reduced lung
      bacterial burden three days post-challenge compared to mice that received pre
      immunization plasma. Based on our results, OprF(311-341)-OprI-A- and B-flagellin
      fusion proteins are highly effective in mice and nonhuman primates and thus merit
      additional development as a potential vaccine for use in humans.

PMID- 19744587
TI  - Tracking epitope-specific antiviral CD4+ T cell responses to a live attenuated
      vaccine reveals ongoing functional responses.
AB  - There are few studies that have examined the frequencies of epitope-specific
      CD4(+) T cells following the use of a highly effective vaccine, yet such data
      would potentially be of value for the development of novel vaccination
      strategies. In this study we tracked human epitope-specific CD4(+) T cell
      responses over time after immunisation with a live attenuated varicella zoster
      virus vaccine by MHC Class II tetrameric complexes and functional assays. We show
      that the peptide-specific responses reflect those against whole virus antigens,
      and are similar in both frequency and phenotype to those found in healthy
      volunteers, despite a highly attenuated and clinically inapparent infection.

PMID- 19744588
TI  - Region of interest analysis: by selecting regions with denuded areas can we
      detect greater amounts of change?
AB  - INTRODUCTION: Based on recent analyses, the measures of short-term responsiveness
      of magnetic resonance imaging (MRI) derived cartilage morphometry may not be as
      large as earlier studies had suggested. We examined if by selecting regions of
      interest with denuded cartilage, the remaining cartilage within this region of
      interest was susceptible to greater rates of cartilage loss. METHODS: Subjects
      included for this analysis are a subset of the approximately 4700 participants in
      the Osteoarthritis Initiative (OAI) Study. Bilateral radiographs and 3T MRI
      (Siemens Trio) of the knees and clinical data are obtained at baseline and
      annually in all participants. Hundred and fifty subjects from the OAI progression
      subcohort all of whom had both frequent symptoms and, in the same knee,
      radiographic osteoarthritis (ROA defined as definite tibio-femoral osteophytes on
      X-ray) based on a screening reading done at the OAI clinics. One knee from each
      subject was selected for analysis. Using sagittal 3D DESSwe MR images from the
      baseline and 12-month follow-up visit, a segmentation algorithm was applied to
      the cartilage plates of the index knee to compute the cartilage volume,
      normalized cartilage volume (volume normalized to bone surface interface area),
      and percent denuded area (Total Cartilage Bone Interface area denuded of
      cartilage). Summary statistics of the changes (absolute and percentage) from
      baseline at 1 year and the standardized response mean (SRM), i.e., mean change
      divided by the standard deviation (SD) of that change were calculated. Analyses
      are stratified into three groups according to baseline assessment of denuded
      area: those with no denuded area in the region of interest at baseline, and then
      two groups (intermediate denuded area (<or=median) and severe (>or=median)
      denuded area) of equal sample size. RESULTS: On average the subjects were 60.9
      years of age and obese with a mean body mass index (BMI) of 30.3 kg/m(2). For the
      combined central medial femur and tibia the mean volume change for the whole
      sample was -48.2 (SD 159.8) mm(3), which gives an SRM of -0.30. In the subsample
      of knees with no denuded area the SRM was -0.25, in the knees with intermediate
      denuded area the SRM was -0.30, and in knees with severe denuded area the SRM was
      -1.00. For normalized volume of the central medial femur in the subsample of
      knees with no denuded area the SRM was -0.22, in the knees with intermediate
      denuded area the SRM was -0.26, and in knees with severe denuded area (n=23) the
      SRM was -0.71. The magnitude of the SRMs was generally smaller in participants
      with no denuded area. In contrast, the SRMs in participants with denuded area
      were larger. CONCLUSION: By selecting participants with the presence of cartilage
      regions with denuded area the ability to demonstrate change in cartilage loss in
      that specific location is markedly improved compared to persons without a full
      thickness lesion in that cartilage plate. This option for screening during
      recruitment in clinical trials could facilitate the detection of participants at
      greater risk of subsequent cartilage loss.

PMID- 19744589
TI  - The support of matrix accumulation and the promotion of sheep articular cartilage
      defects repair in vivo by chitosan hydrogels.
AB  - OBJECTIVE: Chitosan has been widely used as an injectable scaffold in cartilage
      tissue engineering due to its characteristic biocompatibility and
      biodegradability. In this study, chitosan was used in its hydrogel form as a
      scaffold for chondrocytes that act to reconstruct tissue-engineered cartilage and
      repair articular cartilage defects in the sheep model. This study aims to find a
      novel way to apply chitosan in cartilage tissue engineering. METHODS: Temperature
      responsive chitosan hydrogels were prepared by combining chitosan, beta-sodium
      glycerophosphate (GP) and hydroxyethyl cellulose (HEC). Tissue-engineered
      cartilage reconstructions were made in vitro by mixing sheep chondrocytes with a
      chitosan hydrogel. Cell survival and matrix accumulation were analyzed after 3
      weeks in culture. To collect data for in vivo repair, reconstructions cultured
      for 1 day were transplanted to the freshly prepared defects of the articular
      cartilage of sheep. Then at both 12 and 24 weeks after transplantation, the
      grafts were extracted and analyzed histologically and immunohistochemically.
      RESULTS: The results showed that the chondrocytes in the reconstructed cartilage
      survived and retained their ability to secrete matrix when cultured in vitro.
      Transplanted in vivo, the reconstructions repaired cartilage defects completely
      within 24 weeks. The implantation of chitosan hydrogels without chondrocytes also
      helps to repair cartilage defects. CONCLUSIONS: The chitosan-based hydrogel could
      support matrix accumulation of chondrocytes and could repair sheep cartilage
      defects in 24 weeks. This study showcased the success of a new technique in its
      ability to repair articular cartilage defects.

PMID- 19744590
TI  - Nondestructive assessment of sGAG content and distribution in normal and degraded
      rat articular cartilage via EPIC-microCT.
AB  - OBJECTIVE: The objective of this study was to evaluate the feasibility of
      quantifying the Equilibrium Partitioning of an Ionic Contrast agent via
      Microcomputed Tomography (EPIC-microCT) to nondestructively assess sulfated
      glycosaminoglycan (sGAG) content and distribution in rat articular cartilage ex
      vivo, and in doing so to establish a paradigm for extension of this technique to
      other small animal models. DESIGN: After determination of an appropriate
      incubation time for the anionic contrast agent, EPIC-microCT was used to examine
      age-related differences in cartilage sGAG content between 4-, 8-, and 16-week old
      (n=5 each) male Wistar rats and to evaluate sGAG depletion in the right femora of
      each age group after 60 min of digestion with chondroitinase ABC. The EPIC
      microCT measurements were validated by histological safranin-O staining, and
      reproducibility was evaluated by triplicate scans of six femora. RESULTS:
      Cartilage attenuation gradually increased with cumulative digestion time and
      reached a plateau at approximately 60 min with a 16.0% temporal increase
      (P<0.01). Average femoral articular cartilage attenuation increased by 14.2% from
      4- to 8-weeks of age (P<0.01) and further increased by 2.5% from 8 to 16 weeks
      (P<0.05). After 60 min of digestion, femoral articular cartilage attenuations
      increased by 15-17% in each age group (P<0.01). Correspondingly, sGAG optical
      density decreased with age and digestion, and showed a linear correlation (r=
      0.88, slope=-1.26, P<0.01, n=30) with EPIC-microCT cartilage attenuation. High
      reproducibility was indicated by a low coefficient of variation (1.5%) in
      cartilage attenuation. CONCLUSIONS: EPIC-microCT imaging provides high spatial
      resolution and sensitivity to assess sGAG content and three-dimensional
      distribution in rat femoral articular cartilage.

PMID- 19744591
TI  - The State's role and health--swine flu as a case study.

PMID- 19744592
TI  - Contrast-induced nephropathy and nephrogenic systemic fibrosis. Preface.

PMID- 19744593
TI  - Contrast-induced acute kidney injury (CIAKI).
AB  - Injury to the kidney continues to occur following the administration of
      intravascular iodinated contrast media. In this article, the author reviews the
      pathophysiology of contrast-induced acute kidney injury (CIAKI), the relationship
      of CIAKI to long-term adverse outcomes, what type of patients are at risk of
      CIAKI, and how the diagnosis is made. After discussion of the reported incidence
      of CIAKI, an approach to prevention is briefly reviewed.

PMID- 19744594
TI  - Contrast-induced nephropathy after intravenous administration: fact or fiction?
AB  - Recent prospective clinical investigations in high-risk patients receiving
      intravenous contrast media for computed tomography (CT) suggest that the
      incidence and serious negative clinical outcomes are much less common than
      previously believed. Additional perspectives comparing random variations in serum
      creatinine in subjects not receiving contrast media show similar fluctuations
      that would equate to contrast-induced nephrotoxicity (CIN). Putative mechanisms
      for how CIN could cause death or other serious adverse clinical consequences have
      not been elucidated.

PMID- 19744595
TI  - Prevention of contrast-induced nephropathy: an overview.
AB  - Many unknowns remain concerning how best to reduce a patient's risk of contrast
      induced nephropathy (CIN). Many interventions have been proposed, but few have
      gone unchallenged, and new questions have arisen from analysis of serum
      creatinine variations in patients who have not been exposed to radiographic
      iodinated contrast media (RICM). Use of alternate imaging tests that do not use
      RICM is the most direct way to avoid CIN. Hydration remains the bulwark of
      intervention when RICM must be administered. The administration of N
      acetylcysteine is a popular pharmacologic prophylaxis against CIN but its
      efficacy is unclear. Hemodialysis has not been effective, but hemofiltration has
      shown good results in limited series.

PMID- 19744596
TI  - Carbon dioxide in angiography to reduce the risk of contrast-induced nephropathy.
AB  - In the 1970s, Hawkins pioneered the intra-arterial use of carbon dioxide gas for
      high-risk patients who were allergic to iodinated contrast material and for those
      with renal failure. With the advent of digital subtraction angiography in 1980,
      reliable imaging of "low-density" CO(2) contrast agent became available.
      Subsequently, with the addition of high-resolution of digital subtraction
      angiography, stacking software (adding multiple images), tilting tables and a
      reliable, user-friendly delivery system, CO(2) imaging has become nearly
      comparable to and, in some cases, superior to that of iodinated contrast media.
      It is the only safe contrast agent for patients in renal failure, which is
      extremely important in view of the increasing incidence of diabetes and
      complexities of interventional procedures. The low viscosity of CO(2) not only
      improves the sensitivities of several diagnostic procedures but may afford
      advantages for several interventional procedures.

PMID- 19744597
TI  - Nephrogenic systemic fibrosis: history and epidemiology.
AB  - Nephrogenic systemic fibrosis (NSF) is a new disease; the first case was
      diagnosed in 1997. It took 9 years before an association between NSF and
      gadolinium-based contrast agents (Gd-CAs) was identified. Gadolinium has several
      advantages for use in relation to enhanced MRI, but it is also a toxic heavy
      metal. For nearly 20 years, it was believed that Gd-CAs were safe, and they were
      used liberally. The prevalence of NSF cases varies between the various Gd-CAs,
      and adequate documentation of NSF cases after exposure to extracellular Gd-CAs
      remains a problem. All evidence points toward the fact that the real number of
      patients who have NSF has not been accurately totaled; the disease seems to be
      underdiagnosed for various reasons.

PMID- 19744598
TI  - Nephrogenic systemic fibrosis: clinical picture and treatment.
AB  - The classic hallmark symptoms of advanced nephrogenic systemic fibrosis (NSF)
      (skin thickening, hardening and hyperpigmentation, and disabling contractures in
      renal failure patients) in temporal association with Gd-based contrast agent
      (GBCA) exposure are almost pathognomonic of NSF. Less obvious cases may be
      diagnosed on the basis of history of early GBCA-related NSF symptoms (warm
      swellings, pain, discoloration, itching of lower legs), signs of multiorgan
      involvement (lungs, nervous system), the exclusion of differential diagnoses,
      including scleromyxedema and systemic sclerosis, and the histology of deep skin
      biopsies. Symptomatic treatment with intensive physiotherapy and painkillers is
      important, but there is no known curative medical treatment. Spontaneous
      remission of NSF symptoms may occur with recovery of renal function after an
      episode of acute renal failure, or with kidney transplantation of chronic renal
      failure patients.

PMID- 19744599
TI  - Nephrogenic systemic fibrosis: histology and gadolinium detection.
AB  - The association between gadolinium (Gd)-containing MR imaging contrast agents and
      the development of nephrogenic systemic fibrosis (NSF) is well recognized. The
      authors review the histopathologic features, methodology, and results of analysis
      of tissues for Gd in NSF. Scanning electron microscopy/energy dispersive x ray
      spectroscopy (SEM/EDS) provides sensitive detection of individual Gd-containing
      deposits in situ. Secondary ion mass spectroscopy has far greater sensitivity for
      detection of Gd than SEM/EDS and allows correlation at the cellular level.
      Inductively coupled plasma mass spectrometry is the recognized method for full
      quantitative analysis of Gd in tissues but requires destruction of the tissue and
      does not allow spatial correlation. In practice, the different analytic
      techniques provide complementary data and can be selected based on the
      information required.

PMID- 19744600
TI  - Involvement of gadolinium chelates in the mechanism of nephrogenic systemic
      fibrosis: an update.
AB  - Nephrogenic systemic fibrosis (NSF) is a highly debilitating scleroderma-like
      disease occurring exclusively in patients with severe or end-stage renal failure.
      Since the recognition of a link between gadolinium chelates (GCs) used as
      contrast agents for MR imaging and NSF by two independent European teams in 2006,
      numerous studies have described the clinical issues and investigated the
      mechanism of this disease. So far the most commonly reported hypothesis is based
      on the in vivo dechelation of GCs. The physicochemical properties of GCs,
      especially their thermodynamic and kinetic stabilities, are described in the
      present article. High kinetic stability provided by the macrocyclic structure,
      combined with high thermodynamic stability, minimizes the amount of free
      gadolinium released in the body. The current hypotheses regarding the
      pathophysiologic mechanism are critically discussed.

PMID- 19744601
TI  - How to avoid nephrogenic systemic fibrosis: current guidelines in Europe and the
      United States.
AB  - Views vary about how to avoid nephrogenic systemic fibrosis (NSF). In Europe, it
      is contraindicated to use gadodiamide, gadopentetate dimeglumine, and
      gadovertisamide in patients who have a glomerular filtration rate (GFR) of less
      than 30 mL/min, and these agents may only be used with caution in patients who
      have a GFR between 30 and 60 mL/min. Similar restrictions have not been
      introduced for the other six gadolinium-based contrast agents available in the
      European market. In the United States, the US Food and Drug Administration
      introduced a class ban and warned about the use of gadolinium-based contrast
      agents in patients who have reduced renal function. However, European and
      American guidelines about how to avoid NSF are generally not very different.

PMID- 19744602
TI  - Applications of advanced oxidation processes in wastewater treatment.

PMID- 19744603
TI  - Development of ICRP's philosophy on the environment. A report of environmental
      protection: the concept and use of reference animals and plants.

PMID- 19744613
TI  - Pharmacogenetics in cardiovascular antithrombotic therapy.
AB  - Thrombosis is the most important underlying mechanism of coronary artery disease
      and embolic stroke. Hence, antithrombotic therapy is widely used in these
      scenarios. However, not all patients achieve the same degree of benefit from
      antithrombotic agents, and a considerable number of treated patients will
      continue to experience a new thrombotic event. Such lack of clinical benefit may
      be related to a wide variability of responses to antithrombotic treatment among
      individuals (i.e., interindividual heterogeneity). Several factors have been
      identified in this interindividual heterogeneity in response to antithrombotic
      treatment. Pharmacogenetics has emerged as a field that identifies specific gene
      variants able to explain the variability in patient response to a given drug.
      Polymorphisms affecting the disposition, metabolism, transporters, or targets of
      a drug all can be implicated in the modification of an individual's
      antithrombotic drug response and therefore the safety and efficacy of the
      aforementioned drug. The present paper reviews the modulating role of different
      polymorphisms on individuals' responses to antithrombotic drugs commonly used in
      clinical practice.

PMID- 19744614
TI  - Influence of continuous infusion of low-dose human atrial natriuretic peptide on
      renal function during cardiac surgery: a randomized controlled study.
AB  - OBJECTIVES: The purpose of this study was to determine the effect of human atrial
      natriuretic peptide (hANP) in patients who underwent coronary artery bypass
      grafting (CABG) on renal function. BACKGROUND: Acute renal failure after cardiac
      surgery is associated with high morbidity and mortality. METHODS: A total of 504
      patients who underwent CABG were divided into 2 groups: 1 group received hANP at
      0.02 microg/kg/min from the start of cardiopulmonary bypass (hANP group), and 1
      group did not receive hANP (placebo group). Various parameters were measured
      before and after surgery. RESULTS: There was no difference in mortality between
      the 2 groups, but post-operative complications were less frequent in the hANP
      group (p = 0.0208). In the hANP group, serum creatinine (Cr) was significantly
      lower and urinary Cr and Cr clearance were significantly higher from post
      operative day 1 to week 1. The maximum post-operative Cr level and percent
      increase of Cr were significantly lower in the hANP group (p < 0.0001). Patients
      with Cr exceeding 2.0 mg/dl included 1 in the hANP group and 8 in the placebo
      group, showing a significant difference (p = 0.0374). Four patients in the
      placebo group and none in the hANP group required hemodialysis, but the
      difference was not statistically significant. CONCLUSIONS: Continuous infusion of
      low-dose hANP from the start of cardiopulmonary bypass effectively maintained
      post-operative renal function. Infusion of hANP prevents early post-operative
      acute renal failure and helps to achieve safer cardiac surgery. ( CLINICAL TRIAL
      REGISTRATION NUMBER: UMIN000001440).

PMID- 19744615
TI  - Effect of intracoronary streptokinase administered immediately after primary
      percutaneous coronary intervention on long-term left ventricular infarct size,
      volumes, and function.
AB  - OBJECTIVES: The purpose of this study was to investigate the reflections of the
      improvement in microvascular perfusion provided by adjuvant intracoronary
      streptokinase (ICSK) on late-phase infarct size and left ventricular volumes and
      functions. BACKGROUND: It has been shown that ICSK given immediately after
      primary percutaneous coronary intervention (PCI) improves myocardial perfusion in
      the early days of ST-segment elevation acute myocardial infarction. METHODS:
      Ninety-five patients undergoing primary PCI were randomized to ICSK 250 kU (n =
      51) or no additional therapy (n = 44). Two days later, coronary hemodynamic
      indexes were measured to evaluate tissue-level perfusion. After 6 months,
      angiography, echocardiography, and technetium-99m single-photon emission computed
      tomography (SPECT) were performed. RESULTS: At 2 days, all indexes of
      microvascular function were significantly better in the ICSK group than in the
      control group, including coronary flow reserve (2.5 vs. 1.7, p < 0.001) and index
      of microvascular resistance (20.2 vs. 34.2, p < 0.001). At 6 months, infarct size
      (22.7% vs. 32.9%; p = 0.003) and left ventricular end-systolic (41.1 ml vs. 60.9
      ml; p = 0.009) and end-diastolic volumes (95.5 ml vs. 118.3 ml; p = 0.006) were
      significantly smaller, and the ejection fraction was significantly higher (57.2%
      vs. 51.8%; p = 0.018) in the ICSK group compared with the control group.
      CONCLUSIONS: In this study, it has been demonstrated that low-dose ICSK given
      immediately after primary PCI significantly limits long-term infarct size and
      preserves left ventricular volumes and functions. (Effect of Complementary
      Intracoronary Streptokinase Administration Immediately After Primary Percutaneous
      Coronary Intervention on Microvascular Perfusion and Late Term Infarct Size in
      Patients With Acute Myocardial Infarction; NCT00302419).

PMID- 19744616
TI  - Adenosine-induced stress myocardial perfusion imaging using dual-source cardiac
      computed tomography.
AB  - OBJECTIVES: This study sought to determine the feasibility of performing a
      comprehensive cardiac computed tomographic (CT) examination incorporating stress
      and rest myocardial perfusion imaging together with coronary computed tomography
      angiography (CTA). BACKGROUND: Although cardiac CT can identify coronary
      stenosis, very little data exist on the ability to detect stress-induced
      myocardial perfusion defects in humans. METHODS: Thirty-four patients who had a
      nuclear stress test and invasive angiography were included in the study. Dual
      source computed tomography (DSCT) was performed as follows: 1) stress CT:
      contrast-enhanced scan during adenosine infusion; 2) rest CT: contrast-enhanced
      scan using prospective triggering; and 3) delayed scan: acquired 7 min after rest
      CT. Images for CTA, computed tomography perfusion (CTP), and single-photon
      emission computed tomography (SPECT) were each read by 2 independent blinded
      readers. RESULTS: The DSCT protocol was successfully completed for 33 of 34
      subjects (average age 61.4 +/- 10.7 years; 82% male; body mass index 30.4 +/- 5
      kg/m(2)) with an average radiation dose of 12.7 mSv. On a per-vessel basis, CTP
      alone had a sensitivity of 79% and a specificity of 80% for the detection of
      stenosis > or =50%, whereas SPECT myocardial perfusion imaging had a sensitivity
      of 67% and a specificity of 83%. For the detection of vessels with > or =50%
      stenosis with a corresponding SPECT perfusion abnormality, CTP had a sensitivity
      of 93% and a specificity of 74%. The CTA during adenosine infusion had a per
      vessel sensitivity of 96%, specificity of 73%, and negative predictive value of
      98% for the detection of stenosis > or =70%. CONCLUSIONS: Adenosine stress CT can
      identify stress-induced myocardial perfusion defects with diagnostic accuracy
      comparable to SPECT, with similar radiation dose and with the advantage of
      providing information on coronary stenosis.

PMID- 19744617
TI  - Stress computed tomography myocardial perfusion: steps, questions, and layers.

PMID- 19744618
TI  - Comparative efficacy of dronedarone and amiodarone for the maintenance of sinus
      rhythm in patients with atrial fibrillation.
AB  - OBJECTIVES: We sought to compare the efficacy and safety of dronedarone versus
      amiodarone for the prevention of recurrent atrial fibrillation (AF). BACKGROUND:
      Dronedarone is a noniodinated amiodarone congener developed to maintain sinus
      rhythm. Few data are available to directly compare the efficacy and safety of
      dronedarone versus amiodarone. METHODS: We conducted a systematic overview of all
      randomized controlled trials in which the authors evaluated dronedarone or
      amiodarone for the prevention of AF. The effect of amiodarone versus dronedarone
      was summarized by the use of indirect comparison meta-analysis and normal
      logistic meta-regression models. RESULTS: We identified 4 placebo-controlled
      trials of dronedarone, 4 placebo-controlled trials of amiodarone, and 1 trial of
      dronedarone versus amiodarone. By using random-effects modeling, we found that
      there was a significant estimated reduction in recurrent AF with amiodarone
      versus placebo (odds ratio [OR]: 0.12; 95% confidence interval [CI]: 0.08 to
      0.19) but not dronedarone versus placebo (OR: 0.79; 95% CI: 0.33 to 1.87). A
      normal logistic regression model incorporating all trial evidence found
      amiodarone superior to dronedarone (OR: 0.49; 95% CI: 0.37 to 0.63; p < 0.001)
      for the prevention of recurrent AF. In contrast, these models also found a trend
      toward greater all-cause mortality (OR: 1.61; 95% CI: 0.97 to 2.68; p = 0.066)
      and greater overall adverse events requiring drug discontinuation with amiodarone
      versus dronedarone (OR: 1.81; 95% CI: 1.33 to 2.46; p < 0.001). CONCLUSIONS:
      Dronedarone is less effective than amiodarone for the maintenance of sinus
      rhythm, but has fewer adverse effects. For every 1,000 patients treated with
      dronedarone instead of amiodarone, we estimate approximately 228 more recurrences
      of AF in exchange for 9.6 fewer deaths and 62 fewer adverse events requiring
      discontinuation of drug.

PMID- 19744619
TI  - Amiodarone or dronedarone for atrial fibrillation: too early to know the winner?

PMID- 19744620
TI  - Prospective validation of the prognostic usefulness of brain natriuretic peptide
      in asymptomatic patients with chronic severe mitral regurgitation.
AB  - OBJECTIVES: The purpose of the study was to determine the independent and
      additive prognostic value of brain natriuretic peptide (BNP) in patients with
      severe asymptomatic mitral regurgitation and normal left ventricular function.
      BACKGROUND: Early surgery could be advisable in selected patients with chronic
      severe mitral regurgitation, but there are no criteria to identify candidates who
      could benefit from this strategy. Assessment of BNP has not been studied in
      asymptomatic patients with severe mitral regurgitation; hence, its prognostic
      value remains unclear. METHODS: We prospectively evaluated 269 consecutive
      patients with severe asymptomatic organic mitral regurgitation and left
      ventricular ejection fraction above 60%. The first 167 consecutive patients
      served as the derivation cohort, and the following 102 patients served as a
      validation cohort. The combined end point was the occurrence of either symptoms
      of congestive heart failure, left ventricular dysfunction, or death at follow-up.
      RESULTS: The end point was reached in 35 (21%) patients of the derivation set and
      in 21 (20.6%) patients of the validation cohort. The receiver-operating
      characteristics curve yielded an optimal cutoff point of 105 pg/ml of BNP that
      was able to discriminate patients at higher risk in both cohorts (76% vs. 5.4%
      and 66% vs. 4.0%, respectively). In both sets, BNP was the strongest independent
      predictor by multivariate analysis. CONCLUSIONS: Among patients with severe
      asymptomatic organic mitral regurgitation, BNP > or =105 pg/ml discriminates a
      subgroup of patients at higher risk. Because of its incremental prognostic value,
      BNP assessment should be considered in clinical routine workup for risk
      stratification.

PMID- 19744621
TI  - B-type natriuretic peptide and echocardiography in the surveillance of severe
      mitral regurgitation prior to valve surgery.

PMID- 19744622
TI  - Incidence of sudden cardiac death in China: analysis of 4 regional populations.

PMID- 19744623
TI  - Images in cardiology. Cardiac hemangioma.

PMID- 19744625
TI  - Sunitinib in breast cancer: friend or foe.

PMID- 19744626
TI  - Early experience with sunitinib, combined with docetaxel, in patients with
      metastatic breast cancer.
AB  - Sunitinib malate (SUTENT) is an oral, multitargeted tyrosine kinase inhibitor
      that blocks several pathways central to angiogenesis and tumor cell proliferation
      and migration, including vascular endothelial growth factor receptors (VEGFRs)
      and platelet-derived growth factor receptors (PDGFRs). Sunitinib has demonstrated
      clinical activity as a single agent in patients with metastatic breast cancer and
      it is hypothesized that enhanced clinical benefit may be derived by combining
      sunitinib with chemotherapy or other targeted agents. The current report
      describes four patients with advanced/metastatic breast cancer who experienced
      clinically meaningful responses following treatment with sunitinib in combination
      with docetaxel.

PMID- 19744627
TI  - Endosonography in gastroenterology. Preface.

PMID- 19744628
TI  - Choice of endosonographic equipment and normal endosonographic anatomy.
AB  - Endosonography may be considered as a very special area in endoscopy. It really
      revolutionised endoscopy in allowing seeing behind the digestive lumen, in
      accessing the mediastinum and the pancreas, and in performing the first "NOTES"
      procedures. Endoscopists have usually mixed feelings towards endosonography: most
      of them consider EUS as the "Holy Grail" since it is one of the most complex
      diagnostic and therapeutic endoscopic procedures, but many users are still
      uncomfortable with some anatomical landmarks and with the choice of equipment.
      Echoendoscopes are indeed known to be costly and fragile, and quite versatile
      with the choice between different manufacturers, and between radial or linear
      (convex array) oriented instruments. This review aims at providing up-to-date
      information on the different types of echoendoscopes and processors and on normal
      endosonographic anatomy of the digestive tract, the mediastinum, the pancreas and
      the biliary tree.

PMID- 19744629
TI  - Endosonography of high-grade intra-epithelial neoplasia/early cancer.
AB  - Endosonography (EUS) is frequently used for staging of early malignant
      gastrointestinal lesions. High-grade intra-epithelial neoplasia (HGIN) and
      mucosal cancer have a very low risk for lymphatic metastasis and therefore are
      suitable for endoscopic therapy. In HGIN and early oesophageal and gastric
      cancer, high-frequency miniprobes can provide detailed imaging of the different
      layers. However, diagnostic accuracy differentiating between mucosal and
      submucosal disease is not sufficient, and therefore (diagnostic) endoscopic
      resection should be performed in all localisable lesions to detect submucosal
      cancer at risk for lymph node metastasis. EUS for lymph node staging is
      considered to be the method with the highest accuracy, especially compared with
      computed tomography.

PMID- 19744630
TI  - Endosonographic staging of upper intestinal malignancy.
AB  - Numerous studies conducted over the last 25 years provide evidence on the high
      diagnostic accuracy and important role of endoscopic ultrasonography (EUS) in
      staging oesophageal and gastric carcinoma. This extensive research was recently
      subjected to metaanalyses, condensing our knowledge on EUS performance and
      facilitating its comparison with competing methods. It is, however, important to
      realise that the management of oesophageal and gastric carcinoma is evolving and
      so are staging algorithms, setting new challenges for EUS and re-defining its
      position. Restaging after neoadjuvant treatment and precise assessment of early
      carcinoma before endoscopic treatment are areas of growing interest, but the role
      of EUS in these settings is rather limited. Rapidly developing cross-sectional
      imaging has the potential to challenge the position of EUS as the most accurate
      method in loco-regional staging. On the other hand, EUS guided fine-needle
      aspiration offers the unique opportunity to obtain cytological confirmation of
      lymph node metastases, with future potential for molecular staging.

PMID- 19744631
TI  - Endosonographic staging of lower intestinal malignancy.
AB  - The use of EUS in the assessment of rectal pathology is well established. The
      accurate staging of lower intestinal tumours predicts prognosis and guides the
      planning of individual patient treatment. Increased experience and the
      development of high resolution three-dimensional EUS has lead to the greater
      accuracy of rectal staging with EUS of rectal tumours now considered the gold
      standard showing T stage accuracy that ranges from 75% to 95%, with N stage
      accuracy ranging from 65% to 80%. The use of EUS in the staging of colonic
      pathology, however, is not so well established though advances in miniprobe EUS
      has improved the assessment of colonic tumours. EUS is also of benefit in the
      assessment of anal pathology though here, accurate correlation with histology has
      not been firmly established.

PMID- 19744632
TI  - The impact of EUS in primary gastric lymphoma.
AB  - Gastric lymphoma is the most frequent site of gastrointestinal lymphoma and is
      accessible for endosonographic evaluation. Most primary gastric lymphomas are
      classified as mucosa-associated lymphoid tissue (MALT)-type lymphomas that
      develop in the course of chronic Helicobacter pylori infection. Endoscopic
      ultrasonography (EUS) is regarded to be the most accurate method for the local
      staging of gastric lymphoma, although scientific evidence is limited. In stage
      uEI1 low-grade lymphoma, EUS is able to predict a high chance for cure by H.
      pylori eradication. The significance of EUS elastography or EUS-guided fine
      needle aspiration biopsy to diagnose nodal involvement has not been investigated
      in prospective series yet. Since high-grade lymphoma is always treated as a
      systemic disease, the impact of endosonographic staging is lower than in low
      grade lymphoma. After treatment of primary gastric lymphoma, EUS produces
      conflicting results that are not as accurate as endoscopy with biopsy. Therefore,
      EUS is not mandatory during follow-up.

PMID- 19744633
TI  - The role of endosonography in submucosal tumours.
AB  - Submucosal tumours (SMTs) are relatively common findings in patients undergoing
      endoscopy, especially in upper gastrointestinal (GI) tract. This term includes
      various non-neoplastic and neoplastic conditions. Endoscopic ultrasonography
      (EUS) is the best imaging procedure to characterise SMT and to determine the need
      for further explorations. In this review, the following issues will be addressed:
      the endosonographic features of SMT; the diagnostic accuracy of EUS; the ability
      of EUS to distinguish benign and malignant SMTs; the value of EUS-guided fine
      needle aspiration (FNA); and the influence of EUS on clinical management.

PMID- 19744634
TI  - Endosonography in the management of biliopancreatic disorders.
AB  - Over the past two decades, endoscopic endosonography (EUS) has evolved into an
      indispensible diagnostic and therapeutic utility in the diagnosis and treatment
      of patients with pancreatobiliary disease. In this article, we summarise its
      current potential and provide an update of the latest literature.

PMID- 19744635
TI  - Endosonography in bronchopulmonary disease.
AB  - The diagnostic approach to diseases of the mediastinum is divided into two
      phases: (1) imaging techniques and (2) procedures for obtaining tissue samples
      for cytologic and histologic examination. The latter has for many years
      represented a considerable challenge to the clinician. Often invasive procedures
      in general anaesthesia as mediastinoscopy or thoracoscopy have been necessary.
      However, the sampling of tissue from the mediastinum has been revolutionized by
      EBUS and EUS, since they give access to the middle and the posterior compartment
      via the trachea and the oesophagus, respectively. Both EUS FNA and EBUS-TBNA of
      mediastinal nodes and tumors can provide a specimen adequate for interpretation
      in over 95% of cases with a specificity of close to 100% and a sensitivity
      ranging between 88% and 96%. A growing number of studies including randomized
      trails and meta-analyses have demonstrated a major impact of EUSFNA as well as
      EBUS-TBNA on management of patients with lung cancer as well as in patients with
      unknown lesions in the mediastinum. The aim of the present review is to discuss
      the current role of endosonography in bronchopulmonary diseases focusing on
      endosonographically guided biopsy via the esophagus, trachea and main bronchi.
      The concept of complete echo-endoscopic staging of lung cancer is postulated as
      virtually all mediastinal nodes as well as regions relevant to pulmonal medicine
      (liver and adrenal glands) can be reached by these two methods in combination.

PMID- 19744636
TI  - Intraductal ultrasonography (IDUS) for the diagnosis of biliopancreatic diseases.
AB  - Intraductal ultrasonography (IDUS) is an imaging modality having unique
      characteristics and suitable for imaging of a narrow ductal cavity, its wall and
      the neighbouring structures. As IDUS uses high-frequency ultrasound (12-30MHz),
      its image quality is very high within approximately 2-cm range of radius. The
      bile duct and the pancreatic duct, therefore, are good targets for the assessment
      by IDUS. Biliopancreatic IDUS is mainly performed through the papilla of Vater in
      the same session as endoscopic retrograde cholangiopancreatography (ERCP).
      Biliary IDUS is possible through the percutaneous transhepatic route as well. Not
      many comparative studies on biliopancreatic IDUS have been published. Gallbladder
      IDUS as well as most pancreatic IDUS are still at the level of clinical research.
      Constant delineation of Oddi's sphincter with the improvement of instruments will
      expand the use of IDUS for the assessment of the papilla of Vater lesions.

PMID- 19744637
TI  - Endoscopic ultrasound-guided fine-needle aspiration biopsy and trucut biopsy in
      gastroenterology - An overview.
AB  - Endoscopic ultrasound (EUS)-guided biopsies are reliable, safe and effective
      techniques in obtaining samples for cytological or histological examinations
      either as a primary procedure or in cases where other biopsy techniques have
      failed. Endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA), as
      well as endoscopic ultrasound-guided trucut biopsy (EUS-TCB), has proven to be of
      significant value in the diagnostic evaluation of benign and malignant diseases,
      as well as in staging of the malignant tumours of the gastrointestinal tract and
      of adjacent organs. The diagnostic yield of EUS-guided biopsies depends on site,
      size and characteristics of target tissues as well as technical and procedural
      factors (type of needle, biopsy technique and material processing). Other
      weighting factors include expertise, training and interaction between the
      endosonographer and cytopathologist. Rapid on-site cytological evaluation has
      proven to be successful in optimising the diagnostic efficiency of EUS-FNA. A
      sensible alternative is to collect specimens for histological and
      immunohistochemical investigations in addition to the cytological smears. EUS-FNA
      using a 22-gauge needle is successful in harvesting core biopsies in
      approximately three out of four cases. Therefore, the use of 19-gauge needles for
      EUS-FNA or EUS-TCB may only be necessary in selected cases. The reproducibility
      of cytopathological diagnosis among pathologists with special experience in
      assessing material obtained by EUS-guided biopsies is very high. False-positive
      diagnosis of malignancy in EUS-guided biopsy is rare. False-negative diagnosis
      appears with variable frequency depending on the target tissue, technical factors
      and expertise of the endosonographer and cytopathologist. There are numerous
      challenges and pitfalls in the differential diagnostic classification of benign
      and malignant lesions. These problems are related to the characteristics of
      samples obtained by EUS-guided biopsy, as well as to the multiple diagnoses with
      similar or overlapping cytological or histological characteristics. The high
      prognostic and therapeutic relevance of the cytopathological diagnoses resulting
      from EUS-guided biopsy calls for a shared responsibility of an endosonographer
      and a cytopathologist.

PMID- 19744638
TI  - Coeliac plexus neurolysis.
AB  - Coeliac plexus neurolysis (CPN) has been performed for nearly 100 years to try
      and control pancreatic pain. In recent years endoscopic ultrasound (EUS)-guided
      CPN has become the preferred technique for this procedure yet relatively little
      data exists to support its superiority over other methods. Recent studies have
      demonstrated the potential for direct EUS-guided injection into coeliac ganglia
      as a means to improve efficacy of CPN. This article describes the technique of
      EUS-CPN, the evidence supporting its use and recent advances in this procedure.

PMID- 19744639
TI  - Contrast-enhanced endoscopic ultrasound and elastosonoendoscopy.
AB  - Until recently, there was no contrast harmonic imaging technique available for
      EUS examination. Second-generation US contrast agents produce harmonic signals at
      lower acoustic powers and, therefore, are suitable for EUS imaging at low
      acoustic powers. CE-EUS could provide a contribution to the differential
      diagnosis between a primary pancreatic carcinoma, chronic pancreatitis and a
      pancreatic metastasis, and therefore can have a decisive influence on the
      selection of appropriate therapeutic strategies (follow-up, chemotherapy or
      surgery, for example). However, histology remains the standard in the
      differential diagnosis of pancreatic tumours. Regarding lymph nodes, CE-EUS
      cannot replace EUS-guided fine-needle aspiration. Elastography examines the
      elastic properties of tissues by applying a slight compression to the tissue and
      comparing an image obtained before and after this compression. EUS elastography
      is a new application in the field of endosonography and seems to be able to
      differentiate fibrous and benign tissue from malignant lesions. While our results
      are very encouraging, further research will be needed to further define the place
      of this new technique and should be aimed at further defining criteria for
      accurate elastography as well as subsequently assessing the technique using
      multiple operators in a blinded setting. EUS-guided sonoelastography has the
      potential for further guiding the diagnosis and therapy of gastrointestinal
      related tumours.

PMID- 19744640
TI  - Role of endosonography in drainage of fluid collections and other NOTES
      procedures.
AB  - Endosonography (EUS) has become the accepted procedure for drainage of pancreatic
      fluid collections in the past decade. EUS was shown to be safe and effective and
      it has been the first-line therapy for uncomplicated pseudocysts. Where walled
      off pancreatic necrosis was originally thought to be a contraindication for
      endoscopic treatment, multiple case series have now shown that these fluid
      collections also can be treated endoscopically with low morbidity and mortality.
      Analogous to the treatment of pancreatic fluid collections, others, such as
      abscesses in the lower and upper abdomen, have also been treated successfully,
      although there is limited literature in this regard, EUS appears to be a useful
      technique in natural orifice transluminal endoscopic surgery (NOTES) procedures
      as well.

PMID- 19744641
TI  - Compilation of PZC and IEP of sparingly soluble metal oxides and hydroxides from
      literature.
AB  - The values of PZC and IEP of metal oxides reported in the literature are affected
      by the choice of the specimens to be studied. The specimens, which have PZC and
      IEP similar to the "recommended" value, are preferred by the scientists. The
      biased choice leads to accumulation of results for a few specimens, and the other
      specimens are seldom studied or they are subjected to washing procedures aimed at
      shift of the original IEP toward the "recommended" value. Taking the average or
      median of all published PZC and IEP for certain oxide as the "recommended" value
      leads to substantiation of previously published results due to overrepresentation
      of certain specimens in the sample.

PMID- 19744642
TI  - Who should benefit from diabetes cell therapy?
AB  - Type 1 diabetes are intrinsically unstable conditions because of the loss of both
      insulin secretion and glucose sensing. Guidelines to treat type 1 diabetes have
      become stricter since the Diabetes Control and Complications Trial (DCCT) results
      demonstrated the close relationship between microangiopathy and HbA1c levels,
      whereas the deleterious role of glucose variability on macroangiopathy has been
      more recently suspected. Therapeutic strategies first require the treatment of
      underlying organic causes of the brittleness whenever possible and, secondly, the
      optimization of insulin therapy using analogues, multiple injections and
      consideration of continuous subcutaneous insulin infusion. Alternative approaches
      may still be needed for the most severely affected patients, including islet
      transplantation. We propose islet after kidney transplantation in diabetic
      patients with end-stage kidney disease ineligible for double kidney-pancreas
      transplantation (i.e C peptide negative patients over 45 years of age or with
      severe macroangiopathy) if creatinine blood levels are stable below 20mg/l at
      least six months after kidney transplantation and steroid discontinuation. Islet
      transplantation alone is proposed to (1) C peptide negative diabetic patients,
      (2) aged 18-65 with a duration of diabetes of at least five years, (3) treated
      with intensive subcutaneous insulin therapy, but unable to obtain a glycated
      hemoglobin level below 7% without hypoglycemia and / or with brittleness and
      unpredictable hyper- and hypoglycemia altering quality of life, (4) with normal
      body weight (< 80 kg) and / or low daily insulin needs (the lower, the better),
      (5) with renal function close to normal (creatinine clearance above 60 ml/min
      with albuminuria lower than 300 mg/24 h), (6) with no desire for pregnancy in
      women. Currently and until more complete assessment of the 5-year overall benefit
      risk ratio, islet transplantation remains a clinical research procedure. As
      already provided for other types of transplantation, and once recognized as a
      "routine" procedure, prioritization of enlisted patients for islet
      transplantation could be aided by the calculation of a score that should be
      determined by a multidisciplinary team.

PMID- 19744643
TI  - F-18 FDG PET detection of a medullary thyroid carcinoma in a patient with
      metastatic colonic cancer; literature review.
AB  - OBJECTIVE: We report a case of a medullary thyroid carcinoma discovered by F-18
      fluorodeoxyglucose-positron emission tomography (F-18 FDG PET). PATIENT AND
      METHODS: A 73-year-old man with a history of surgical removal of sigmoid colon
      cancer underwent F-18 FDG PET to search for distant metastases and / or local
      recurrence because of elevated CEA level and new episode of occlusion. F-18 FDG
      PET images showed increased focal FDG uptake in the right lobe of the thyroid.
      Thyroid ultrasound showed one thyroid nodule in each lobe. RESULTS: The fine
      needle aspiration result was suspicious and calcitonin level was elevated. The
      subject underwent thyroidectomy without lymph node dissection. The pathology
      showed a 14 mm medullary thyroid carcinoma. There was no germline mutation of
      RET. CONCLUSIONS: F-18 FDG PET can detect primitive or secondary malignant
      thyroid tumors. Thus, thyroid incidentaloma revealed by 18 FDG PET uptake always
      necessitates careful evaluation.

PMID- 19744644
TI  - Do mechanical tests of glove stiffness provide relevant information relative to
      their effects on the musculoskeletal system? A comparison with surface
      electromyography and psychophysical methods.
AB  - The main purpose of the present study was to test the construct validity of two
      mechanical tests of glove stiffness using a surface electromyography (SEMG)
      methodology that would allow estimating the effect of glove stiffness on forearm
      muscle activation during a standardized grip contraction. The mechanical tests
      [free-deforming multidirectional test (FDMT) and Kawabata Evaluation System for
      Fabrics (KESF)] were applied on 27 gloves covering a wide range of stiffness. In
      30 human subjects, a psychophysical assessment of these gloves was also carried
      on in addition to the SEMG test. The results showed that the sensitivity of the
      different tests to glove stiffness differences was slightly better for the FDMT
      (75% sensitivity) than for the psychophysical assessment (72%), while the SEMG
      test showed much lower sensitivity (13-31%, depending on the muscle). The SEMG
      test was highly correlated to the psychophysical assessment (0.88-0.95, depending
      on the muscle tested), and the FDMT (0.88-0.94) and KESF (0.77-0.86) mechanical
      tests, showing the construct validity of mechanical tests, particularly for the
      FDMT. It was concluded that mechanical tests provide relevant information
      relative to the effect of glove stiffness on the musculoskeletal system of the
      forearm.

PMID- 19744645
TI  - Supramolecular hydrogels formed from biodegradable ternary COS-g-PCL-b-MPEG
      copolymer with alpha-cyclodextrin and their drug release.
AB  - On the basis of the synthesis of novel biodegradable amphiphilic MPEG-b-PCL
      grafted chitooligosaccharide (COS-g-PCL-b-MPEG) copolymers, supramolecular
      hydrogels were fabricated rapidly via their inclusion complexation with alpha
      cyclodextrin (alpha-CD) in aqueous solutions. The graft copolymers were
      characterized by (1)H NMR spectroscopy, gel permeation chromatography (GPC), and
      fluorescence measurement, and the supramolecular structure of the resultant
      hydrogels was confirmed by X-ray diffraction measurements. Rheological studies of
      as-obtained hydrogels indicate that the physical properties could be modulated by
      controlling the concentration and the graft content of the graft copolymers as
      well as the molar feed ratio of the graft to alpha-CD. The in vitro release
      kinetics studies of bovine serum albumin (BSA) entrapped in the hydrogels show
      that the drug release profiles are dependent on the supramolecular hydrogel
      compositions.

PMID- 19744646
TI  - Molecular dynamics studies of the conformation of sorbitol.
AB  - Molecular dynamics simulations of a 3 molal aqueous solution of D-sorbitol (also
      called D-glucitol) have been performed at 300 K, as well as at two elevated
      temperatures to promote conformational transitions. In principle, sorbitol is
      more flexible than glucose since it does not contain a constraining ring.
      However, a conformational analysis revealed that the sorbitol chain remains
      extended in solution, in contrast to the bent conformation found experimentally
      in the crystalline form. While there are 243 staggered conformations of the
      backbone possible for this open-chain polyol, only a very limited number were
      found to be stable in the simulations. Although many conformers were briefly
      sampled, only eight were significantly populated in the simulation. The carbon
      backbones of all but two of these eight conformers were completely extended,
      unlike the bent crystal conformation. These extended conformers were stabilized
      by a quite persistent intramolecular hydrogen bond between the hydroxyl groups of
      carbon C-2 and C-4. The conformational populations were found to be in good
      agreement with the limited available NMR data except for the C-2-C-3 torsion
      (spanned by the O-2-O-4 hydrogen bond), where the NMR data support a more bent
      structure.

PMID- 19744647
TI  - Cell phenotyping in saliva of individuals under psychological stress.
AB  - Total leukocytes, NK cells, B and T lymphocytes present in the saliva of medical
      students with or without stress were quantified by flow cytometry in 10,000
      events. The symptoms of psychological stress were monitored with Lipp's Inventory
      of Stress Symptoms for Adults (ISSL). No significant differences were observed in
      the number of cells phenotyped in students with and those without psychological
      stress. However, a negative correlation was observed between the number of NK
      cells and T lymphocytes in students with stress (r=-0.8173; p=0.0058), suggesting
      that innate immunity is predominant in the adaptation phase.

PMID- 19744648
TI  - [Treatment of vascular decompression of the duodenum by reimplantation of the
      superior mesenteric artery].

PMID- 19744649
TI  - Predictive knowledge of stimulus relevance does not influence top-down
      suppression of irrelevant information in older adults.
AB  - Our ability to focus attention on task-relevant stimuli and ignore irrelevant
      distractions is reflected by differential enhancement and suppression of neural
      activity in sensory cortices. Previous research has shown that older adults
      exhibit a deficit in suppressing task-irrelevant information, the magnitude of
      which is associated with a decline in working memory performance. However, it
      remains unclear if a failure to suppress is a reflection of an inability of older
      adults to rapidly assess the relevance of information upon stimulus presentation
      when they are not aware of the relevance beforehand. To address this, we recorded
      the electroencephalogram (EEG) in healthy older participants (aged 60-80 years)
      while they performed two different versions of a selective face/scene working
      memory task, both with and without prior knowledge as to when relevant and
      irrelevant stimuli would appear. Each trial contained two faces and two scenes
      presented sequentially followed by a 9 sec delay and a probe stimulus.
      Participants were given the following instructions: remember faces (ignore
      scenes), remember scenes (ignore faces), remember the xth and yth stimuli (where
      x and y could be 1st, 2nd, 3rd or 4th), or passively view all stimuli. Working
      memory performance remained consistent regardless of task instructions. Enhanced
      neural activity was observed at posterior electrodes to attended stimuli, while
      neural responses that reflected the suppression of irrelevant stimuli was absent
      for both tasks. The lack of significant suppression at early stages of visual
      processing was revealed by P1 amplitude and N1 latency modulation indices. These
      results reveal that prior knowledge of stimulus relevance does not modify early
      neural processing during stimulus encoding and does not improve working memory
      performance in older adults. These results suggest that the inability to suppress
      irrelevant information early in the visual processing stream by older adults is
      related to mechanisms specific to top-down suppression.

PMID- 19744650
TI  - A case of unusual course of adolescent menorrhagia: decidual cast as a side
      effect of treatment.
AB  - OBJECTIVE: To present an unusual side effect of therapy for adolescent
      menorrhagia, with commentary on management options. DESIGN: Case report. SETTING:
      Tertiary gynecologic center. PATIENT(S): A 13-year-old girl presenting with
      profuse uterine bleeding. INTERVENTION(S): Dysfunctional uterine bleeding was
      diagnosed, and pharmacologic therapy with a monophasic oral contraceptive (OC)
      pill was introduced. MAIN OUTCOME MEASURE(S): A large decidual cast occurred
      during treatment. RESULT(S): After finishing therapy with OC followed by three
      cycles of cyclic progestogen, the patient experienced regular menses.
      CONCLUSION(S): A large decidual cast may occur during treatment of adolescent
      menorrhagia with OCs; patients should be informed about this possibility, to
      reduce stress connected with the appearance of this side effect.

PMID- 19744651
TI  - Evidence-based palaeopathology: meta-analysis of PubMed-listed scientific studies
      on ancient Egyptian mummies.
AB  - There is a plethora of published scientific studies on ancient Egyptian mummies.
      Surprisingly, hitherto there is no systematic review of this research, which
      would help to assess the quality of this vast body of published literature and
      thus to increase "evidence" in palaeopathological research. The aim of this study
      was to review all PubMed-listed scientific studies performed on Ancient Egyptian
      mummies. A total of 131 studies were found in the database for the selected time
      period, 1977-2005. Our "meta-analysis" showed that the number of publications per
      year varies enormously. The majority of mummies examined date to the third
      intermediate and Ptolemaic periods; data from other time periods were lacking.
      Identification of the cause of death and (14)C-dating of the mummy or funeral
      goods were rarely addressed. There was a tendency towards an increased use of non
      invasive examination methods in more modern times. Our meta-analysis addressed
      both scientific content (e.g. palaeopathological findings/examination methods)
      and publication issues (e.g. location of the first author or year of publication)
      in these studies. Based on our experience, we recommend some minimum publication
      standards for palaeopathologic studies on ancient mummies, which shall improve
      evidence-based research in palaeopathology in general.

PMID- 19744652
TI  - Classification systems for tibial plateau fractures; does computed tomography
      scanning improve their reliability?
AB  - INTRODUCTION: The purpose of this study was to evaluate the impact of computed
      tomography scanning on the inter- and intra-observer reliability of the OTA/AO,
      the Schatzker, and the Hohl classifications in the assessment of tibial plateau
      fractures. METHODS: Four independent observers classified 45 consecutive
      fractures of the tibial plateau according to the criteria of the OTA/AO system,
      the Schatzker classification, and the Hohl classification. Two sessions of
      readings were compared; first, the use of plain anterior-posterior and lateral X
      rays alone was evaluated, then 4 weeks later the combination of plain X-rays and
      two-dimensional computed tomography scans were evaluated. The readings were
      repeated 8 weeks later to evaluate intra-observer reliability. RESULTS: The three
      classification systems showed "moderate" inter-observer reliability and "good"
      and "moderate" intra-observer reliability when classified solely on the basis of
      plain radiographs. After the addition of computed tomography scans inter-observer
      reliability significantly improved to "good" in all classifications. Likewise,
      intra-observer reliability improved to "good" in all classifications after the
      addition of CT-scans. Statistical analysis showed no significant difference
      regarding inter- and intra-observer agreement between the three classifications.
      CONCLUSIONS: Computed tomography scanning improved the inter- and intra-observer
      reliability of the OTA/AO, the Schatzker, and the Hohl classification. Overall,
      all three classification systems showed "good" inter- and intra-observer
      reproducibility when classified with CT-scans.

PMID- 19744653
TI  - Clinical characteristics and long-term mortality of occult hip fracture elderly
      patients.
AB  - BACKGROUND AND OBJECTIVE: Occult hip fractures (OHF) occur in a minute population
      of patients. Diagnosis is made via magnetic resonance imaging (MRI) or
      alternatively via bone scan. Very little is known about the clinical
      characteristics of OHF patients. Our aim was to characterize the clinical and
      long-term survival of OHF in elderly patients and to determine if a certain
      subgroup of patients would benefit from an MRI investigation following normal or
      equivocal radiography. METHODS: Twenty-nine OHF patients diagnosed by a bone scan
      during 1995-2004 were compared with a control group of 94 randomly chosen hip
      fractured patients diagnosed by plain radiography in the same hospital and during
      the same period. RESULTS: Mean age, women/men ratio, place of residence,
      comorbidities, cognitive and functional status were similar in the OHF and
      control group. Twenty-two (75.9%) and 4 (13.8%) patients in the OHF group had had
      subcapital and intertrochanteric fractures respectively, vs. 41 (43.6%) and 47
      (50%) in the control group (p=0.003). Diagnosis delay in the OHF group was 16.8+/
      26.5 days vs. 2.5+/-2.9 days (p<0.001) in the control group. There were fewer
      operations and complications in the OHF group compared to the control group
      (p<0.001 and p=0.017, respectively). During a 13-year follow-up, no differences
      in survival were found between the two groups nor any differences between those
      operated on and those who were not. CONCLUSIONS: OHF patients have no distinctive
      clinical characteristics or long-term survival. The delay in diagnosing OHF is
      too much long and is probably related to the high prevalence of conservative
      treatment. MRI investigation is recommended whenever OHF are suspected and
      surgical treatment is considered, in order to improve diagnosis and treatment.

PMID- 19744655
TI  - How confident can we be in predicting outcome in patients with a minimal Glasgow
      Coma Score? re: Nijboer et al. Patients beyond salvation? Various categories of
      trauma patients with a minimal Glasgow Coma Score.

PMID- 19744656
TI  - Idiopathic intrauterine myocardial infarction without malformations of the heart
      or coronary vessels as a cause of stillbirth.

PMID- 19744657
TI  - Ensuring patient satisfaction with second-trimester abortion in resource-poor
      settings.
AB  - OBJECTIVE: To evaluate patient satisfaction with the new second-trimester
      abortion services in Nepal. METHOD: Depending on the patient's literacy level, a
      questionnaire was read and filled out by the patient herself or by an
      interviewer. Indicators were developed and assessed to determine the patient's
      experience of the services, focusing on her physical, emotional, and social
      comfort. RESULTS: Satisfaction was found to be high for characteristics
      associated with counseling and the caring attitude of the physician. However,
      dissatisfaction was expressed regarding some aspects of the delivery of care,
      especially the lack of privacy and confidentiality and the absence of a support
      person from the patient's own family. CONCLUSION: The patients described privacy,
      confidentiality, and a support person designated by them as factors that would
      greatly contribute to their satisfaction with the services. Maximizing patient
      satisfaction is necessary for the program's success but will be challenging.

PMID- 19744658
TI  - Influence of buffer composition on the capillary electrophoretic separation of
      carbon nanoparticles.
AB  - Carbon nanoparticles obtained from the flame of an oil lamp were examined by
      means of capillary electrophoresis. The influence of buffer composition on the
      separation of the mixture of negatively charged carbon nanoparticles was studied
      by varying buffer selection, pH, and concentration. The electrophoretic pattern
      was affected by both the co- and counter-ion in the buffer solution, influencing
      selectivity and peak shape. The capillary electrophoretic separations at
      different pH revealed species with large electrophoretic mobilities under a wide
      range of pH. The mobility of selected species in the mixture of nanoparticles
      showed a strong dependence upon the solution ionic strength. The mobility of
      these nanoparticles as a function of ionic strength was compared to classical
      electrokinetic theory, suggesting that under the experimental conditions
      utilized, the species are small, highly charged particles with appreciable zeta
      potentials, even at low pH.

PMID- 19744659
TI  - Analysis of hydrocarbon contamination with membrane-assisted solvent extraction:
      comparison of agitation and sonication methods.
AB  - Membrane-assisted solvent extraction (MASE) coupled to large volume injection was
      applied to the determination of (gasoline-type) hydrocarbon contamination in
      water samples. Hexane was used as acceptor phase. 50 microL extract was injected
      in the programmed temperature vaporizer injector using combined split-splitless
      evaporation. The extraction conditions were optimized both for MASE with
      agitation and for MASE with sonication. In the course of optimization the effect
      of extraction time, extraction temperature, agitation speed, solvent volume, pH,
      ionic strength and the addition of methanol were tested. Over 75% recovery was
      accomplished in the range of diesel oil hydrocarbons (n-C(9)-n-C(24)). The
      developed method was validated. Linearity, accuracy and precision were tested.
      The method showed excellent linearity between 1 and 1000 microgL(-1) for n
      alkanes and between 0.05 and 50 mgL(-1) for gasoline. The method was tested with
      comprehensive GCxGC as well and found to be non-discriminative to all major
      compounds of diesel oil.

PMID- 19744660
TI  - A vascular smooth muscle/cell membrane chromatography-offline-gas
      chromatography/mass spectrometry method for recognition, separation and
      identification of active components from traditional Chinese medicines.
AB  - We describe an analytical method of vascular smooth muscle cell membrane
      chromatography (VSM/CMC) combined with gas chromatography/mass spectrometry
      (GC/MS) for recognition, separation and identification of active components from
      traditional Chinese medicines (TCMs). VSM cells by means of primary culture with
      rat thoracic aortas were used for preparation of the stationary phase in the CMC
      model. Retention components by the VSM-CMC model were collected and then analyzed
      by GC/MS under the optimized conditions in offline conditions. After
      investigating the suitability and reliability of the VSM/CMC-offline-GC/MS method
      using nifedipine and nitrendipine as standard compounds, this method was applied
      in screening active components from the extracts of TCMs such as Radix Angelicae
      Dahuricae (RAD), Rhizomza Seu Radix Notopterygii (RSRN), Radix Glehniae (RG) and
      Fructus Cnidii (FC). Retention components from the extracts in the VSM-CMC model
      were imperatorin and osthole identified by the GC/MS method. In vitro
      pharmacological trials indicated that imperatorin and osthole could concentration
      dependently relax the rat thoracic artery pre-contracted by KCl (P<0.05). The
      maximum relaxation effects (R(max)) were 63+/-5% and 40+/-6% for imperatorin and
      osthole, respectively. The VSM/CMC-offline-GC/MS method is an effective screening
      system that can rapidly detect and enrich target components from a complex sample
      and then accurately identify them.

PMID- 19744661
TI  - Characterization and classification of matrix effects in biological samples
      analyses.
AB  - An exhaustive classification of matrix effects occurring when a sample
      preparation is performed prior to liquid-chromatography coupled to mass
      spectrometry (LC-MS) analyses was proposed. A total of eight different situations
      were identified allowing the recognition of the matrix effect typology via the
      calculation of four recovery values. A set of 198 compounds was used to evaluate
      matrix effects after solid phase extraction (SPE) from plasma or urine samples
      prior to LC-ESI-MS analysis. Matrix effect identification was achieved for all
      compounds and classified through an organization chart. Only 17% of the tested
      compounds did not present significant matrix effects.

PMID- 19744662
TI  - Development of a high-performance liquid chromatography-fluorescence detection
      method for analyzing nonylphenol/dinonylphenol-polyethoxylate-based phosphate
      esters.
AB  - A novel reversed phase HPLC method for the simultaneous analysis of surfactants
      containing nonylphenol/dinonylphenol-polyethoxylates and their o-phosphate esters
      is reported, in which eluting substances are detected fluorescently. Their
      chemical structures were elucidated by direct infusion electrospray-mass
      spectrometry in positive mode. The limits of quantification and range of the
      method were determined to be 0.1mg and 0.1-100 mg surfactant L(-1), respectively,
      with a reproducibility (RSD) at a concentration of 38 mg surfactant L(-1) of
      5.6%. The accuracy was determined by spiking selected process water samples with
      known amounts of surfactant, and recoveries were typically in the 82-102% range.

PMID- 19744663
TI  - Determination of endocrine-disrupting chemicals in the liquid and solid phases of
      activated sludge by solid phase extraction and gas chromatography-mass
      spectrometry.
AB  - The highly complex matrix of activated sludge in sewage treatment plants (STPs)
      makes it difficult to detect endocrine-disrupting chemicals (EDCs) which are
      usually present at low concentration levels. To date, no literature has reported
      the concentrations of steroid estrogens in activated sludge in China and very
      limited data are available worldwide. In this work, a highly selective and
      sensitive analytical method was developed for simultaneous determination of two
      classes of EDCs, including estrone (E1), 17beta-estradiol (E2), estriol (E3), 17
      alpha-ethynylestradiol (EE2), 4-nonylphenol (NP) and bisphenol A (BPA), in the
      liquid and solid phases of activated sludge. The procedures for sample
      preparation, extracts derivatization, and gas chromatography-mass spectrometry
      (GC-MS) quantification were all optimized to effectively determine target EDCs
      while minimizing matrix interference. The developed method showed good
      calibration linearity, recovery, precision, and a low limit of quantification
      (LOQ) for all selected EDCs in both liquid and solid phases of activated sludge.
      It was successfully applied to determine the concentrations of EDCs in activated
      sludge samples from two STPs located in Beijing and Shanghai of China,
      respectively.

PMID- 19744664
TI  - Comparison of adsorption of Remazol Black B and Acidol Red on microporous
      activated carbon felt.
AB  - The adsorption of two anionic dyes, Remazol Black B (RB5) and Acidol Red 2BE-NW
      (AR42), onto a microporous activated carbon felt was investigated. The
      characterization of carbon surface chemistry by X-ray microanalysis, Boehm
      titrations, and pH-PZC measurements indicates that the surface oxygenated groups
      are mainly acidic. The rate of adsorption depends on the pH and the experimental
      data fit the intraparticle diffusion model. The pore size distribution obtained
      by DFT analysis shows that the mean pore size is close to 1nm, which indicates
      that a slow intraparticle diffusion process control the adsorption. The
      adsorption isotherms were measured for different pH values. The Khan and the
      Langmuir-Freundlich models lead to the best agreement with experimental data for
      RB5 and AR42, respectively. These isotherm simulations and the pH dependence of
      adsorption show that the adsorption capacity is mainly controlled by
      nondispersive electrostatic interactions for pH values below 4. The adsorption
      kinetics, the irreversibility of the process, and the influence of the pH
      indicate that the rate of adsorption in this microporous felt proceeds through
      two steps. The first one is fast and results from direct interaction of dye
      molecules with the external surface of the carbon material (which account for 10%
      of the whole surface area); in the second, slow step, the adsorption rate is
      controlled by the slow diffusion of dye molecules into the narrow micropores. The
      influence of temperature on the adsorption isotherms was studied and the
      thermodynamic parameters were obtained. They show that the process is spontaneous
      and exothermic.

PMID- 19744665
TI  - Spontaneous dewetting-induced residue-free patterning at room temperature.
AB  - A lithographic patterning method is presented that is based on dewetting induced
      by sequential molding under an applied pressure. Because of spontaneous dewetting
      taking place, the window to be opened is free from any residue and the surface
      exposure is instantaneously assured. This residue-free patterning can be
      accomplished without any heating process and surface treatment, irrespective of
      pattern duty ratio. The residue-free patterning is made possible with the use of
      a rigiflex mold and a roller that is used to bring about pressure-induced
      thinning leading to spontaneous dewetting. A necessary condition for the method
      is that the spreading coefficient of spin-coated liquid be negative. The exposed
      surface can be utilized as a sacrificial layer for etching of underlying layer
      and/or thin film deposition in a fabrication of electronic and biological
      devices.

PMID- 19744666
TI  - An experimental and modeling study of humic acid concentration effect on H(+)
      binding: Application of the NICA-Donnan model.
AB  - Humic substances are the most abundant components of the colloidal and the
      dissolved fraction of natural organic matter (NOM) and they are characterized by
      a strong binding capacity for both metals and organic pollutants, affecting their
      mobility and bioavailability. The understanding of the humic acidic character is
      the first necessary step for the study of the mechanisms of binding of other
      positively charged soluble metal species by humic molecules. The present work,
      which constitutes part of the Ph.D. thesis of Roza Vidali, reports results on the
      influence of the concentration of humic acids on the binding of protons obtained
      through both an experimental and a modeling approach. A reference purified peat
      humic acid (PPHA) isolated by the International Humic Substances Society (IHSS)
      and a humic acid from a Greek soil (GHA) were experimentally studied at various
      humic acid concentrations, ranging from 20 to 200mgL(-1). The proton binding
      isotherms obtained at different humic acid concentrations have shown that proton
      binding is dependent on the concentration of both humic acids. Proton binding
      experimental data were fitted to the NICA-Donnan model and the model parameter
      values were calculated for humic acid concentrations of 20 and >or=100mgL(-1).
      The results obtained for the NICA-Donnan parameters at humic acid concentrations
      >or=100mgL(-1) are in excellent agreement with those reported in the literature.
      However, these model parameter values cannot be used for modeling and predicting
      cation binding in natural aquatic systems, where humic acid concentrations are
      much lower. Two sets of the NICA-Donnan parameters are reported: one for humic
      acid concentrations of >or=100mgL(-1) and one for humic acid concentration of
      20mgL(-1). The significance of the parameters values for each concentration level
      is also discussed.

PMID- 19744667
TI  - Facile preparation of poly(ethyl alpha-cyanoacrylate) superhydrophobic and
      gradient wetting surfaces.
AB  - Hollow microspheres of poly(ethyl alpha-cyanoacrylate) were prepared via vapor
      phase polymerization using micro-waterdroplets as template and initiator.
      Depending on the ratio of the shell thickness to the radius, the hollow
      microspheres would crimple to form either microballoons or microcups during
      drying. These two types of microparticles were used as building blocks to
      construct surfaces with diverse wettability. The microballoons linked up to form
      a porous-netlike surface which was rough enough to render the surface
      superhydrophobic, while the microcups-built surface showed less hydrophobicity.
      In addition, surfaces consisting of both microparticles with gradual decrease of
      roughness along the length direction were obtained, which presented gradient
      wetting property varied from superhydrophobic to hydrophobic. The as-formed
      superhydrophobic or gradient wetting surfaces may find potential applications in
      biomedical field because of the biocompatibility of poly(ethyl alpha
      cyanoacrylate).

PMID- 19744668
TI  - Parenchymal and vascular lesions in ageing equine brains: histological and
      immunohistochemical studies.
AB  - Many age-related changes are described in the nervous system of different
      species, but detailed studies of brain lesions in ageing horses are lacking. The
      aim of the present study was to systematically characterize lesions in the brains
      of 60 horses aged from 7 to 23 years. No gross changes were present in any brain.
      Microscopically, spongiform changes, lipofuscin storage, corpora amylacea,
      gliosis and satellitosis were common, together with axonal and neuronal
      swellings. The most important findings were the presence of pseudocalcium-calcium
      (pCa-Ca) deposits and arterial wall degeneration. Scanning electron microscopical
      examination of two cases with vascular mineralization revealed marked deposition
      of an amorphous substance in the vessel walls that was probably formed by a
      polyanionic protein matrix and a mineral component. Immunohistochemically,
      numerous axonal spheroids were positively labelled for ubiquitin. No PrPsc was
      detected in sections with neuronal vacuolation. Neuronal swelling, corpora
      amylacea, hippocampal Tau-positive neurons and methenamine-positive diffuse
      (preamyloid) plaques were also detected. Congo red staining failed to detect
      amyloid deposition. The characterization of age-related lesions in the brains of
      these horses will allow these changes to be discriminated from pathological
      processes in future studies. Some lesions described here, including some vascular
      changes, the presence of diffuse plaques and tau accumulation in hippocampal
      neurons, have not been described previously in the horse.

PMID- 19744669
TI  - Occurrence and tissue distribution of porcine circovirus type 2 identified by
      immunohistochemistry in Danish finishing pigs at slaughter.
AB  - Infection with porcine circovirus type 2 (PCV2) may be subclinical or lead to the
      development of porcine circovirus disease (PCVD), which includes the entities of
      post-weaning multisystemic wasting syndrome (PMWS) and the porcine respiratory
      disease complex (PRDC). PCV2 infection and PMWS occur in the early post-weaning
      period and are also recognized in finishing pigs of 12-19 weeks of age. The aim
      of the present study was to assess the role of PCV2 infection in disease of
      finishing pigs. Accordingly, the occurrence and tissue distribution of PCV2 was
      examined in Danish finishing pigs at the time of slaughter. Multiple lymph nodes
      and the spleen, lungs and kidneys from 136 pigs with PRDC (case group) and 36
      pigs without lung lesions (control group) were examined by immunolabelling for
      the presence of PCV2. Additionally, follicular dendritic cells (FDC) were
      identified immunohistochemically. One or more tissues of 61% of the pigs were
      positive for PCV2 antigen. Up to 78% of the pigs had mild lymphoid depletion,
      indistinct lymphoid follicles and/or histiocytic infiltration of the lymph nodes,
      but these lesions were not associated with PCV2. No association was found between
      the presence of lung or kidney lesions and detection of PCV2. Three distinct
      patterns of cellular PCV2 antigen labelling were recognized: (1) labelling of
      cells with stellate morphology and reticular distribution, (2) labelling of
      isolated non-epithelial, cells, and (3) epithelial labelling. The reticular
      pattern was most common and localized to the centres of lymphoid follicles,
      corresponding to the morphology and distribution of FDCs. This observation may be
      interpreted to suggest that PCV2 may interact with FDCs to cause depletion of B
      lymphocytes. Alternatively, the FDCs may be a reservoir of infective PCV2 in
      subclinically infected animals or represent a simple storage site for PCV2
      antigen in pigs that have recovered from infection.

PMID- 19744671
TI  - Pulmonary artery ligation with lung preservation in Behcet disease: report of a
      case with prolonged survival.

PMID- 19744672
TI  - Reconstruction of the pulmonary artery for lung cancer: long-term results.
AB  - OBJECTIVE: Reconstruction of the pulmonary artery in association with lung
      resection is technically feasible with low morbidity and mortality. To assess
      long-term outcome, we report our 20-year experience. METHODS: Between 1989 and
      2008, we performed pulmonary artery reconstruction in 105 patients with non-small
      cell lung cancer (tangential resections not included). Twenty-seven patients
      received induction therapy. We performed 47 pulmonary artery sleeve resections,
      55 reconstructions by pericardial patch (with 3 left pneumonectomies under
      cardiopulmonary bypass), and 3 by pericardial conduit. In 65 patients, a
      bronchial sleeve resection was associated; in 6 cases superior vena caval
      reconstruction was also required. Fifteen patients had stage IB disease, 37 stage
      II, 31 IIIA, and 22 IIIB. Sixty-one patients had epidermoid carcinoma, and 38
      adenocarcinoma. Mean follow-up was 46 +/- 40 months. RESULTS: The procedure
      related complications were 1 pulmonary artery thrombosis requiring completion
      pneumonectomy and 1 massive hemoptysis leading to death (operative mortality,
      0.95%); 28 patients had other complications, with the most frequent prolonged air
      leakage. Overall 5-year survival was 44%. Five- and 10-year survivals for stages
      I and II versus stage III were, respectively, 60% versus 28% and 25% versus 12%.
      Five-year survivals were 52.6% for N0 and N1 nodal involvement versus 20% for N2;
      10-year survivals were 28% versus 3%. Multivariate analysis yielded induction
      therapy, N2 status, adenocarcinoma, and isolated pulmonary artery reconstruction
      as negative prognostic factors. CONCLUSIONS: Pulmonary artery reconstruction is
      safe, with excellent long-term survival. Our results support this technique as an
      effective option for patients with lung cancer.

PMID- 19744673
TI  - Fifteen years of experience with ATS mechanical heart valve prostheses.
AB  - BACKGROUND: ATS Medical, Inc, developed a mechanical heart valve that has been in
      use since 1992. In this article, we present the results of 15 years of follow-up
      of patients who have undergone ATS heart valve replacement at our hospital.
      METHODS AND RESULTS: We performed ATS heart valve replacements on 231 patients
      between September 1993 and March 2008. Our operative mortality rate for the study
      period was 2.2%. The survival for postoperative thromboembolic events was
      0.29%/pt-y for aortic valve replacement, 0.48%/pt-y for mitral, 0.80%/pt-y for
      double valve replacement, and overall 0.44%/pt-y. The survival after bleeding
      events was 0.29%/pt-y for aortic valve replacement, 0.16%/pt-y for mitral, 0%/pt
      y for double valve replacement, and overall 0.19%/pt-y. Patient-prosthesis
      mismatch, as determined by echocardiography, was found in 83.3% of patients at 19
      mm, but other sizes showed good valve function. Prosthetic valve noise was
      undetectable in 92.8% of patients, and quality of life was excellent.
      CONCLUSIONS: Few prosthetic valve-related complications were seen with ATS heart
      valve replacements in this study, and the follow-up results were favorable. The
      international normalized ratio was maintained in the range 1.6 to 2.0 in patients
      with aortic valve replacement in sinus rhythm. Not only bleeding events, seen at
      a rate of 0.19%/pt-y, but also thromboembolic events, at 0.44%/pt-y, were low
      when compared with conventional mechanical valves. Prosthetic valve noise is low,
      and this appears to be an excellent mechanical valve from the quality of life
      standpoint. The ATS valve has an excellent safety profile when compared with
      other mechanical valves.

PMID- 19744675
TI  - Foraminiferal assemblages in Biscayne Bay, Florida, USA: responses to urban and
      agricultural influence in a subtropical estuary.
AB  - This study assessed foraminiferal assemblages in Biscayne Bay, Florida, a heavily
      utilized estuary, interpreting changes over the past 65 years and providing a
      baseline for future comparisons. Analyses of foraminiferal data at the genus
      level revealed three distinct biotopes. The assemblage from the northern bay was
      characterized by stress-tolerant taxa, especially Ammonia, present in low
      abundances ( approximately 2.0 x 10(3) foraminifers/gram) though relatively high
      diversity ( approximately 19 genera/sample). The southwestern margin of the bay
      was dominated by Ammonia and Quinqueloculina, an assemblage characterized by the
      lowest diversities ( approximately 12 genera/sample) and highest abundances (
      approximately 1.1 x 10(4) foraminifers/gram), influenced by both reduced salinity
      and elevated organic-carbon concentrations. A diverse assemblage of smaller
      miliolids and rotaliids ( approximately 26 genera/sample) characterized the open
      bay assemblage, which also had a significant component ( approximately 10%) of
      taxa that host algal endosymbionts. In the past 65 years, populations of symbiont
      bearing taxa, which are indicators of normal-marine conditions, have decreased
      while stress-tolerant taxa, especially Ammonia spp., have increased in
      predominance.

PMID- 19744674
TI  - Predictive value of the National Institutes of Health Stroke Scale and the Mini
      Mental State Examination for neurologic outcome after coronary artery bypass
      graft surgery.
AB  - OBJECTIVE: We intended to define the role of the National Institutes of Health
      Stroke Scale and the Mini-Mental State Examination in identifying adverse
      neurologic outcomes in a large international sample of patients undergoing
      cardiac surgery. METHODS: We evaluated 4707 patients undergoing cardiac surgery
      with cardiopulmonary bypass at 72 centers in 17 countries between November 1996
      and June 2000. Prespecified overt neurologic outcomes were categorized as type I
      (clinically diagnosed stroke, transient ischemic attack, encephalopathy, or coma)
      or type II (deterioration of intellectual function). The National Institutes of
      Health Stroke Scale and Mini-Mental State Examination were administered
      preoperatively and on postoperative day 3, 4, or 5. Receiver operating
      characteristic curves were plotted to determine the predictive value of worsening
      in National Institutes of Health Stroke Scale and Mini-Mental State Examination
      scores with respect to type I and II outcomes. RESULTS: The receiver operating
      characteristic area under the curve for changes in National Institutes of Health
      Stroke Scale score (n = 4620) was 0.89 for type I outcomes and 0.66 for type II
      outcomes. A 1-point worsening in National Institutes of Health Stroke Scale score
      provided excellent discrimination (86% specificity; 84% sensitivity) of type I
      outcomes. The receiver operating characteristic area under the curve for changes
      in Mini-Mental State Examination score (n = 4707) was 0.75 for type I outcomes
      and 0.71 for type II outcomes. A 2-point worsening in Mini-Mental State
      Examination score provided only fair discrimination (73% specificity; 62%
      sensitivity) of type II outcomes. CONCLUSION: We used baseline controls and
      postoperative worsening in National Institutes of Health Stroke Scale and Mini
      Mental State Examination scores to predict both serious adverse neurologic
      outcome and deterioration of intellectual function. Our findings provide the only
      reference for evaluating these tests that are used in cardiac surgical clinical
      trials.

PMID- 19744676
TI  - [Somatic perineal pain other than pudendal neuralgia].
AB  - In addition to the well-established syndrome of pudendal compression, and given
      the rich nerve trunk innervation of the perineum, pain originating in other nerve
      trunks can occur and must be remembered. Nerves originating high in the
      thoracolumbar area (ilioinguinal nerve, iliohypogastric nerve, genitor femoral
      nerve) can be the seat of traumatic lesions occurring during surgical approaches
      through the abdominal wall or can undergo compressions when crossing the fascia
      of the large abdominal muscles. Misleading perineal irradiations do not resemble
      pudendal neuralgia and should suggest pain in these trunks whose cutaneous
      territories are not solely perineal and whose clinical expression as pain is does
      not occur in the seated position. Similarly, painful minor intervertebral
      dysfunction of the thoracolumbar junction is not simply in the mind and should be
      considered, searched for, and treated. Related more to pudendal neuralgia, pain
      in the inferior cluneal nerve, triggered by the seated position, should be
      considered when the pain reaches the lateral anal region, the scrotum, or the
      labia majora but not involving the glans penis or the clitoris. Specific
      treatments (physical therapy, infiltrations, surgery) have proven effective.

PMID- 19744677
TI  - [Pathologic characteristics of the most frequent peripheral nerve tumors].
AB  - Benign tumors of the peripheral nerves come from ectodermic tissues. This chapter
      describes the most common forms: the schwannomas and the neurofibromas.
      Schwannomas have two possible patterns of cells: Antoni A and B types.
      Neurofibromas are most often associated with neurofibromatosis NF1 and may be
      localized, diffuse, or plexiform. The benign tumor structures account for the
      fact that they can be removed with or without preserving the concerned nerve.
      Malignant tumors (malignant peripheral sheath tumors) come from degeneration of
      neurofibromas in two out of three cases and have a poor prognosis.

PMID- 19744678
TI  - [Buttocks sciatic pain].
AB  - Confusion between radicular and nerve trunk syndrome is not rare. With sciatic
      pain, any nerve trunk pain or an atypical nerve course should suggest nerve trunk
      pain of the sciatic nerve in the buttocks. The usual reflex with sciatic pain is
      vertebral-radicular conflict. The absence of spinal symptoms and the beginning of
      pain in the buttocks and not in the lumbar region should reorient the etiologic
      search. Once a tumor of the nerve trunk has been ruled out (rarely responsible
      for pain other than that caused by tumor pressure), a myofascial syndrome should
      be explored searching for clinical, electrophysiological, and radiological
      evidence of compression of the sciatic trunk by the piriform muscle but also the
      obturator internus muscle. Hamstring syndrome may be confused with this syndrome.
      Treatment is first and foremost physical therapy. Failures can be treated with
      classical CT-guided infiltrations with botulinum toxin. Surgery should only be
      entertained when all these solutions have failed.

PMID- 19744679
TI  - 'Setting the guinea pigs free': towards a new model of community-led social
      marketing.
AB  - OBJECTIVES: To offer the opportunity to discuss the positive contribution of co
      production approaches in the field of social marketing. STUDY DESIGN: Recognizing
      the ever-evolving theoretical base for social marketing, this article offers a
      brief commentary on the positive contribution of co-production approaches in this
      field. The authors outline their own move towards conceptualizing a community-led
      social marketing approach and describe some key features. This developing
      framework has been influenced by, and tested through, the Early Presentation of
      Cancer Symptoms Programme, a community-led social marketing approach to tackle
      health inequalities across priority neighbourhoods in North East Lincolnshire,
      UK. METHODS: A blend of social marketing, community involvement and rapid
      improvement science methodologies are drawn upon. The approach involves not just
      a strong focus on involving communities in insight and consultation, but also
      adopts methods where they are in charge of the process of generating solutions.
      RESULTS: A series of monthly and pre/post measures have demonstrated improvements
      in awareness of symptoms, reported willingness to act and increases in
      presentation measured through service referrals. Key features of the approach
      involve shared ownership and a shift away from service-instigated change by
      enabling communities 'to do' through developing skills and confidence and the
      conditions to 'try out'. CONCLUSIONS: The approach highlights the contribution
      that co-production approaches have to offer social marketing activity. In order
      to maximize potential, it is important to consider ways of engaging communities
      effectively. Successful approaches include translating social marketing
      methodology into easy-to-use frameworks, involving communities in gathering and
      interpreting local data, and supporting communities to act as change agents by
      planning and carrying out activity. The range of impacts across organisational,
      health and social capital measures demonstrates that multiple and longer-lasting
      improvements can be achieved with successful approaches.

PMID- 19744680
TI  - [Is there also a crisis in radiology?].

PMID- 19744681
TI  - [2010. The Spanish society's publications: Radiologia and much more].

PMID- 19744682
TI  - [The "sarcoid cluster sign". A new sign in high resolution chest CT].
AB  - OBJECTIVES: To evaluate the presence of clusters of multiple small punctiform
      nodules in the peripheral regions of the lung in patients with sarcoidosis, and
      to report this finding as a new sign "the sarcoid cluster sign" in high
      resolution chest CT (HRCT). MATERIAL AND METHODS: This is a retrospective study
      of the HRCT findings in 91 patients diagnosed with lung sarcoidosis at our
      hospital. We evaluated the presence of clusters of multiple small punctiform
      nodules in the periphery of the lungs (the "sarcoid cluster sign"), whether these
      were rounded or long in shape, and their distribution in the lung fields. We used
      reconstructions of maximum intensity projections (MIP). We correlated the imaging
      and histopathological results in three patients. Afterward, we evaluated the
      presence of the "sarcoid cluster sign" on high resolution CT findings in 120
      consecutive patients studied for suspected diffuse lung disease. RESULTS: The
      "sarcoid cluster sign" was present at HRCT in 9 of the 91 patients with
      sarcoidosis (6 men and 3 women; mean age 29 years). Most clusters were rounded
      and most were located in the non-subpleural peripheral regions of the upper and
      middle fields of the lungs. When the clusters were located in the subpleural
      peripheral regions, the clusters contained small subpleural nodules. The
      correlation between the imaging and histopathological results revealed that the
      clusters corresponded to noncaseous, noncoalescing granulomas with a predominance
      of CD4+ lymphocytes, without fibrosis, that were distributed in the lymph
      vessels. Only 2 of the 120 patients with suspected diffuse lung disease had
      peripheral clusters of multiple small punctiform nodules (the "sarcoid cluster
      sign"); these two patients had sarcoidosis, and a total of 21 cases of
      sarcoidosis were diagnosed in this group. CONCLUSION: The "sarcoid cluster sign"
      on HRCT has been observed only in young patients with lung sarcoidosis. This
      finding could be useful in the diagnosis in the diagnosis of this disease.

PMID- 19744683
TI  - Genetic diversity of porcine circovirus type 2 from pigs in Republic of Korea.
AB  - Porcine circovirus type 2 (PCV2) is the causative agent of postweaning
      multisystemic wasting syndrome (PMWS). In this study, 38 PCV2 cases obtained from
      different pig farms with different health conditions in Republic of Korea were
      sequenced and analyzed. Phylogenetic analysis showed that our cases had a greater
      variation and the existence of two PCV2 groups with at least four subgroups (1A,
      1C, 2D, and 2E). Most cases obtained from PMWS-affected herds were in group 1,
      whereas cases with no clinical signs compatible with PMWS (wasted non-PMWS) were
      included within group 2. Moreover, four cases from the wasted non-PMWS belonged
      to PCV2-group 1. Therefore, our results suggest that PCV2-group 1 is more related
      to PMWS than group 2.

PMID- 19744684
TI  - [Cognitive rehabilitation in multiple sclerosis: preliminary results and
      presentation of a new program, PROCOG-SEP].
AB  - BACKGROUND: Although cognitive disorders are well-known in multiple sclerosis
      (MS), even in earlier stages of the disease, their management may be overlooked.
      Our objective was to elaborate and evaluate the efficiency of a remedial program
      (PROCOG-SEP) designed for MS patients. The evidence-based program proposes
      exercises to both stimulate preserved functions and develop new abilities
      compensating for cognitive disabilities. DESIGN/METHODS: Twenty-four patients
      with MS participated in 10/2-hour PROCOG-SEP sessions over a 6-month period. A
      neuropsychologist recorded BCcog-SEP performances before and after the PROCOG-SEP
      program. In addition, the same neuropsychologist conducted psychoclinical
      interviews to complete the before and after cognitive evaluations. The
      statistical analysis used the t-test performed with Excel. RESULTS: Compared with
      the initial levels, subtests of BCcog-SEP showing improvement after PROCOG-SEP
      were: verbal memory (SRT), visuospatial memory (10/36), verbal fluency (animal
      categories) and response to conflicting orders. Also, individual psychological
      interviews tended to be in favor of a general improvement in quality of life
      (more social interactions for instance). CONCLUSIONS/RELEVANCE: To our knowledge,
      the management program we have elaborated is the first designed to improve
      cognitive deficits in MS. These encouraging results suggest possibilities for
      improving cognition and thus quality-of-life in MS patients.

PMID- 19744685
TI  - Molecular evidence for Anaplasma phagocytophilum in Ixodes ricinus from Turkey.
AB  - This study investigated the presence of the pathogen Anaplasma phagocytophilum in
      ixodid ticks removed from humans living in three provinces (Giresun, Trabzon,
      Rize) in the east of the Black Sea Region of Turkey. A total of 1097 ixodid ticks
      were examined for the presence of A. phagocytophilum DNA. From the 95 pooled tick
      samples tested, species-specific fragments of A. phagocytophilum (11/95 samples,
      11.6%) were amplified by nested PCR. Adult Ixodes ricinus (9/53 samples, 17.0%)
      and Ixodes spp. nymphs (2/9 samples, 22.2%) were infected with A.
      phagocytophilum. None of the remaining tick species gave a positive result for
      the presence of the pathogen. All nested PCR-positive samples were directly
      sequenced. The partial sequences (457bp) of the amplicons obtained from the
      infected tick pools were 100% identical to one another and to previously isolated
      sequences from human patients. To obtain a longer 16S rRNA gene sequence, one
      representative sample was reamplified with the universal primer set. The longer
      representative sequence (1306bp) also shared 99.92% similarity (a single adenine
      deletion) with the recently reported complete sequence of A. phagocytophilum.

PMID- 19744686
TI  - Selective infection of CD4+ effector memory T lymphocytes leads to preferential
      depletion of memory T lymphocytes in R5 HIV-1-infected humanized NOD/SCID/IL
      2Rgammanull mice.
AB  - To investigate the events leading to the depletion of CD4(+) T lymphocytes during
      long-term infection of human immunodeficiency virus type 1 (HIV-1), we infected
      human CD34(+) cells-transplanted NOD/SCID/IL-2Rgamma(null) mice with CXCR4-tropic
      and CCR5-tropic HIV-1. CXCR4-tropic HIV-1-infected mice were quickly depleted of
      CD4(+) thymocytes and both CD45RA(+) naive and CD45RA(-) memory CD4(+) T
      lymphocytes, while CCR5-tropic HIV-1-infected mice were preferentially depleted
      of CD45RA(-) memory CD4(+) T lymphocytes. Staining of HIV-1 p24 antigen revealed
      that CCR5-tropic HIV-1 preferentially infected effector memory T lymphocytes
      (T(EM)) rather than central memory T lymphocytes. In addition, the majority of
      p24(+) cells in CCR5-tropic HIV-1-infected mice were activated and in cycling
      phase. Taken together, our findings indicate that productive infection mainly
      takes place in the activated T(EM) in cycling phase and further suggest that the
      predominant infection in T(EM) would lead to the depletion of memory CD4(+) T
      lymphocytes in CCR5-tropic HIV-1-infected mice.

PMID- 19744687
TI  - The effect of the vaccinia K1 protein on the PKR-eIF2alpha pathway in RK13 and
      HeLa cells.
AB  - Activated PKR protein regulates downstream anti-viral effects, including
      inhibition of translation. Thus, many viruses encode proteins to inhibit PKR.
      Here, we provide evidence that the vaccinia virus K1 protein, a host-range
      protein, possesses this function. First, the expression of the wild-type K1
      protein was necessary to inhibit virus-induced eIF2alpha phosphorylation, an
      indirect measure of PKR activation, in RK13 and HeLa cells. Second, virus-induced
      eIF2alpha phosphorylation no longer occurred in PKR-deficient HeLa cells,
      suggesting PKR was responsible for vaccinia virus-induced eIF2alpha modification.
      Third, in normal HeLa cells, K1 protein expression also prevented virus-mediated
      PKR phosphorylation (activation). Residues in the C-terminal portion of the ANK2
      region of K1 were identified as necessary for this inhibitory phenotype.
      Interestingly, mutant viruses that failed to inhibit PKR activation, such as
      S2C#2, also did not replicate in HeLa cells, suggesting that K1's inhibition of
      PKR was required for a productive infection. In support of this theory, when PKR
      was absent from HeLa cells, there was a modest restoration of viral protein
      synthesis during S2C#2 infection. However, the increased protein synthesis was
      insufficient for a productive infection.

PMID- 19744688
TI  - In vitro incorporation of the phage Phi29 connector complex.
AB  - The incorporation of the DNA packaging connector complex during lambdoid phage
      assembly in vivo is strictly controlled-one and only one of the twelve identical
      icosahedral vertices is differentiated by the inclusion of a portal or connector
      dodecamer. Proposed control mechanisms include obligate nucleation from a
      connector containing complex, addition of the connector as the final step during
      assembly, and a connector-mediated increase in the growth rate. The inability to
      recapitulate connector incorporation in vitro has made it difficult to obtain
      direct biochemical evidence in support of one model over another. Here we report
      the development an in vitro assembly system for the well characterized dsDNA
      phage Phi29 which results in the co-assembly of connector with capsid and
      scaffolding proteins to form procapsid-like particles (PLPs). Immuno-electron
      microscopy demonstrates the specific incorporation of connector vertex in PLPs.
      The connector protein increases both the yield and the rate of capsid assembly
      suggesting that the incorporation of the connector in Phi29 likely promotes
      nucleation of assembly.

PMID- 19744689
TI  - Nuclear dynamics of influenza A virus ribonucleoproteins revealed by live-cell
      imaging studies.
AB  - The negative sense RNA genome of influenza A virus is transcribed and replicated
      in the nuclei of infected cells by the viral RNA polymerase. Only four viral
      polypeptides are required but multiple cellular components are potentially
      involved. We used fluorescence recovery after photobleaching (FRAP) to
      characterise the dynamics of GFP-tagged viral ribonucleoprotein (RNP) components
      in living cells. The nucleoprotein (NP) displayed very slow mobility that
      significantly increased on formation of transcriptionally active RNPs.
      Conversely, single or dimeric polymerase subunits showed fast nuclear dynamics
      that decreased upon formation of heterotrimers, suggesting increased interaction
      of the full polymerase complex with a relatively immobile cellular component(s).
      Treatment with inhibitors of cellular transcription indicated that in part, this
      reflected an interaction with cellular RNA polymerase II. Analysis of mutated
      influenza virus polymerase complexes further suggested that this was through an
      interaction between PB2 and RNA Pol II separate from PB2 cap-binding activity.

PMID- 19744690
TI  - Cross-reactive monoclonal antibodies to multiple HIV-1 subtype and SIVcpz
      envelope glycoproteins.
AB  - The extraordinarily high level of genetic variation of HIV-1 env genes poses a
      challenge to obtain antibodies that cross-react with multiple subtype Env
      glycoproteins. To determine if cross-reactive monoclonal antibodies (mAbs) to
      highly conserved epitopes in HIV-1 envelope glycoproteins can be induced, we
      immunized mice with wild-type or consensus HIV-1 Env proteins and characterized a
      panel of ten mAbs that reacted with varying breadth to subtypes A, B, C, D, F, G,
      CRF01_AE, and a highly divergent SIVcpzUS Env proteins by ELISA and Western blot
      analysis. Two mAbs (3B3 and 16H3) cross-reacted with all tested Env proteins,
      including SIVcpzUS Env. Surface plasmon resonance analyses showed both 3B3 and
      16H3 bound Env proteins with high affinity. However, neither neutralized primary
      HIV-1 pseudoviruses. These data indicate that broadly reactive non-neutralizing
      monoclonal antibodies can be elicited, but that the conserved epitopes that they
      recognize are not present on functional virion trimers. Nonetheless, such mAbs
      represent valuable reagents to study the biochemistry and structural biology of
      Env protein oligomers.

PMID- 19744691
TI  - Complement modulates pathogenesis and antibody-dependent neutralization of West
      Nile virus infection through a C5-independent mechanism.
AB  - Although the interactions of complement and viruses have been widely studied, the
      function of C5 and the membrane attack complex in the context of viral infection
      or antibody-mediated neutralization remains controversial. Using C5-depleted or 
      deficient human or mouse sera, we show that C5 does not contribute to the
      antibody-dependent or -independent neutralization of West Nile virus (WNV) in
      cell culture. Consistent with this, C5 neither contributed to protection against
      WNV pathogenesis nor augmented the neutralizing efficacy of complement-fixing
      anti-WNV neutralizing antibodies in mice. Although previous studies established
      that activation of the classical, lectin, and alternative complement pathways
      restricts WNV infection, our results show little effect of C5 and by inference
      the terminal lytic complement components. Overall, these results enhance our
      mechanistic understanding of how complement controls flavivirus infections.

PMID- 19744692
TI  - Waste activated sludge fermentation: effect of solids retention time and biomass
      concentration.
AB  - Laboratory scale, room temperature, semi-continuous reactors were set-up to
      investigate the effect of solids retention time (SRT, equal to HRT hydraulic
      retention time) and biomass concentration on generation of volatile fatty acids
      (VFA) from the non-methanogenic fermentation of waste activated sludge (WAS)
      originating from an enhanced biological phosphorus removal process. It was found
      that VFA yields increased with SRT. At the longest SRT (10d), improved biomass
      degradation resulted in the highest soluble to total COD ratio and the highest
      VFA yield from the influent COD (0.14g VFA-COD/g TCOD). It was also observed that
      under the same SRT, VFA yields increased when the biomass concentration
      decreased. At a 10d SRT the VFA yield increased by 46%, when the biomass
      concentration decreased from 13g/L to 4.8g/L. Relatively high nutrient release
      was observed during fermentation. The average phosphorus release was 17.3mg PO(4)
      P/g TCOD and nitrogen release was 25.8mg NH(4)-N/g TCOD.

PMID- 19744693
TI  - PCB dechlorination enhancement in Anacostia River sediment microcosms.
AB  - In situ treatment of PCB contaminated sediments via microbial dechlorination is a
      promising alternative to dredging, which may be reserved for only the most
      contaminated areas. Reductive dechlorination of low levels of weathered PCB
      mixtures typical of urban environments may occur at slow rates. Here, we report
      that biostimulation and bioaugmentation enhanced dechlorination of low
      concentration (2.1 mg PCBs/kg dry weight) historical PCBs in microcosms prepared
      with Anacostia River, Washington, DC, sediment. Treatments included electron
      donors butyrate, lactate, propionate and acetate (1 mM each); alternate
      halogenated electron acceptors (haloprimers) tetrachlorobenzene (TeCB, 25
      microM), pentachloronitrobenzene (PCNB, 25 microM), or 2,3,4,5,6-PCB (PCB116, 2.0
      microM); and/or bioaugmentation with a culture containing Dehalococcoides
      ethenogenes strain 195 (3 x 10(6)cells/mL). Dechlorination rates were enhanced in
      microcosms receiving bioaugmentation, PCNB and PCNB plus bioaugmentation,
      compared to other treatments. Microcosm subcultures generated after 415 days and
      spiked with PCB116 showed sustained capacity for dechlorination of PCB116 in
      PCNB, PCNB plus bioaugmentation, and TeCB treatments, relative to other
      treatments. Analysis of Chloroflexi 16S rRNA genes showed that TeCB and PCNB
      increased native Dehalococcoides spp. from the Pinellas subgroup; however this
      increase was correlated to enhanced dechlorination of low concentration weathered
      PCBs only in PCNB-amended microcosms. D. ethenogenes strain 195 was detected only
      in bioaugmented microcosms and decreased over 281 days. Bioaugmentation with D.
      ethenogenes strain 195 increased PCB dechlorination rates initially, but enhanced
      capacity for dechlorination of a model congener, PCB116, after 415 days occurred
      only in microcosms with enhanced native Dehalococcoides spp.

PMID- 19744694
TI  - Removal of MIB and geosmin using granular activated carbon with and without MIEX
      pre-treatment.
AB  - This study assessed the impact of MIEX pre-treatment, followed by either
      coagulation or microfiltration (MF), on the effectiveness of pilot granular
      activated carbon (GAC) filters for the removal of the taste and odour compounds,
      2-methylisoborneol (MIB) and geosmin, from a surface drinking water source over a
      2-year period. Complete removal of MIB and geosmin was achieved by all GAC
      filters for the first 10 months, suggesting that the available adsorption
      capacity was sufficient to compensate for differences in dissolved organic carbon
      (DOC) entering the GAC filters. Reduction of empty bed contact time (EBCT), in
      all but one GAC filter, resulted in breakthrough of spiked MIB and geosmin, with
      initial results inconclusive regarding the impact of MIEX pre-treatment. MIB and
      geosmin removal increased over the ensuing 12 months until complete removal of
      both MIB and geosmin was again achieved in all but one GAC filter, which had been
      pre-chlorinated. Autoclaving and washing the GAC filters had minimal impact on
      geosmin removal but reduced MIB removal by 30% in all but the pre-chlorinated
      filter, confirming that biodegradation impacted MIB removal. The impact of
      biodegradation was greater than any impact on GAC adsorption arising from DOC
      differences due to MIEX pre-treatment. It is not clear whether, at a lower
      initial EBCT, MIEX pre-treatment may have impacted on the adsorption capacity of
      the virgin GAC. The GAC filter maintained at the longer EBCT, which was also pre
      chlorinated, completely removed MIB and geosmin for the period of the study,
      suggesting that the greater adsorption capacity was compensating for any decrease
      in biological degradation.

PMID- 19744695
TI  - Effect of dairy manure rate and the stabilization time of amended soils on
      atrazine degradation.
AB  - The application rate of liquid cow manure (LCM) in the field and the
      stabilization time of amended soils before application of pre-plant herbicides
      are factors that determine their efficiency. This study includes evaluation of
      residual atrazine (2-chloro-4-ethylamino-6-isopropylamino-1,3,5-triazine) in soil
      and amended soils with equivalent rate of 100,000; 200,000; and 300,000 L ha(-1)
      of LCM and the effect of pre-incubation time of amended soils on atrazine
      degradation. The study was carried out under controlled conditions using an
      Andisol with previous historical application of atrazine. The respiratory
      activity and fluorescein diacetate (FDA) studies indicated that the time
      necessary for stabilization of amended soils is over 20-30 d. During the
      measurement of respiratory and FDA activity, no significant differences were
      observed when atrazine was applied. The half-life of atrazine ranged from 5 to 8d
      and the relative distribution of degradation products seem to be affected by the
      application of LCM. The pre-incubation time of amended soil and LCM dose would
      not affect atrazine degradation rate, when the soil has a history of herbicide
      application. However, repeated applications of LCM in a long period of time could
      change the soil pH and increase the content of dissolved organic carbon (DOC)
      which could further contribute to a faster degradation of atrazine. Both effects
      would reduce the effectiveness of atrazine in weed control.

PMID- 19744696
TI  - Specific profiles of perfluorinated compounds in surface and drinking waters and
      accumulation in mussels, fish, and dolphins from southeastern Brazil.
AB  - Despite the concern over widespread distribution of perfluorinated compounds
      (PFCs) even in sparsely populated regions of the world, few studies have reported
      their occurrence in South America. In this study, PFCs were measured in Rio de
      Janeiro State in southeast Brazil: in drinking water from various districts in
      the State, in river water and tucuxi dolphins from the Paraiba do Sul River,
      several species of fish from the State, and mussels from Guanabara Bay. Liver,
      kidney, and muscle from fishes were analyzed to enable an understanding of the
      tissue distribution of PFCs. PFOS, PFOA, and PFHxS were detected in all drinking
      water samples in concentration ranges of 0.58-6.70, 0.35-2.82, and 0.15-1.00 ng
      L(-1), respectively. The profiles of PFCs in drinking water from Brazil (with
      PFOS concentrations comparable to or higher than those of PFOA) were different
      from the profiles that have been reported for other countries. In fish,
      concentrations of PFOS were, in general, higher in liver than in muscle.
      Concentrations of PFOA in livers of fish were similar to or lower than fish
      muscle tissue concentrations. PFOS and PFOA were found in brown mussels from
      Guanabara Bay. Bioconcentration factors (BCFs) of PFOA calculated for mussels
      were higher than the BCFs calculated for fishes. Elevated concentrations of
      PFUnDA (mean: 109+/-17.4 ng g(-1) wet weight) were found in mussels from certain
      locations within Guanabara Bay. Although PFCs were detected in all types of
      samples analyzed, the concentrations were generally lower than the concentrations
      reported for Japan and the USA.

PMID- 19744697
TI  - Environmental risk assessment of antibiotics: an intensive care unit analysis.
AB  - Hospital effluents have been usually known by the microbiological pollution they
      cause, but only recently they have been considered a significant source of
      aquatic environmental pollution due to the presence of medicines in these
      effluents. In this context, an environmental risk assessment (ERA) is presented
      for the most used intravenous antibiotics in the Intensive Care Unit (ICU) of a
      hospital in Curitiba (Brazil). The amount of antibiotics used in the ICU was
      evaluated during 18months (June 2006 until November 2007), in order to calculate
      the Predicted Environmental Concentration (PEC1). Antibiotic excretion data (on
      its original form) and the removal of the selected drugs in the sewage treatment
      plants based on the activated sludge system were used to calculate, respectively,
      PEC2 and PEC2r. The Predicted No-Effect Concentration (PNEC) of pharmaceuticals
      was also considered to assess the environmental risk by calculating the PEC/PNEC
      ratios. All PECs were 1ngL(-1). The worst-case PEC estimations (PEC1 and PEC2)
      were observed for sodic ceftriaxone, sodic cefazolin, meropenem, ampicillin,
      cefepime and sodic piperacillin. PEC/PNEC ratios showed that, given the present
      pattern of usage, high aquatic environmental risk is expected for these
      antibiotics. Further studies should be carried out to elucidate their
      contribution to increasing antimicrobial multi-drug-resistant species.

PMID- 19744699
TI  - Chimpanzee nest distribution and site reuse in a dry habitat: implications for
      early hominin ranging.
AB  - This paper reports on a 20-month study of chimpanzee nesting patterns in Issa,
      Ugalla, western Tanzania. Ugalla is one of the driest, most open, and seasonal
      habitats where chimpanzees are found. The methods used were ethoarchaeological,
      as the chimpanzees were not habituated and behavioural observations were rare.
      Systematic data on the spatial and temporal distribution of nests are presented.
      Places with no nests at the beginning of the study, despite being suitable for
      nesting, were used as controls. Similar to other chimpanzee study sites, nests
      were highly concentrated in some parts of the landscape. Issa chimpanzees
      preferred to nest on slopes. They extensively used the woodland vegetation type
      of their habitat for nesting throughout the annual cycle. Ninety percent of nest
      sites were used repeatedly throughout the study period, but none of the control
      places had nests during this period. The results indicate that chimpanzees ranged
      more widely during the dry season, when food abundance was lowest, food was
      available mainly in open vegetation types, and when drinking water was restricted
      to a few sources. Early hominins in similar habitats may have followed the
      ranging strategy of Issa chimpanzees. As with a previous study, the distribution
      of nests was spatially similar to archaeological distributions in early hominin
      sites. Hominin topography and vegetation type preferences may be misrepresented
      in the archaeological record. Nest sites may have been the antecedents of carcass
      processing sites.

PMID- 19744700
TI  - Treatment of venous thromboembolism in patients with cancer: Guidelines of the
      Italian Society for Haemostasis and Thrombosis (SISET).
AB  - BACKGROUND: The treatment of venous thromboembolism (VTE) in cancer patients
      remains controversial. PURPOSE: The Italian Society for Thrombosis and
      Haemostasis (SISET) commissioned a project to develop clinical practice
      guidelines for the therapy of VTE in patients with malignancies. METHODS: Key
      questions about the treatment of VTE in patients with malignancies were
      formulated by a multidisciplinary working group consisting of experts in clinical
      medicine and research. After a systematic review and discussion of the
      literature, recommendations were formulated and graded according to the
      supporting evidence. For those questions for which the literature search did not
      yield any definitive answer (absence of evidence evidence of low quality, and
      contradictory evidence), a formal consensus method was used to issue clinical
      recommendations. RESULTS: The results of the available literature on VTE
      treatment in cancer patients were reviewed and clinical recommendations were
      drafted. CONCLUSION: We describe the results of a systematic literature review
      and an explicit approach to consensus techniques which resulted in
      recommendations for the key therapeutic issues in cancer patients with VTE.

PMID- 19744701
TI  - Impaired fibrin gel permeability by high homocysteine levels.
AB  - Mechanisms involved in the relationship between hyperhomocysteinemia and
      thrombosis are still unclear. In previous reports we have shown that high
      homocysteine concentrations led to more compact and branched fibrin networks than
      controls. These clots showed an impaired lysis associated to their architecture.
      The aim of this study was to evaluate the effects of homocysteine on permeation
      of clots obtained from plasma and purified systems. Fibrin gels were prepared
      with normal plasma incubated with homocysteine and, in the purified systems, with
      fibrinogen and factor XIII treated with the amino acid. Permeability constants
      (K(s)) were determined through flow measurements. Linear regression curve between
      K(s) values and homocysteine levels in the plasmatic assays showed a negative
      correlation coefficient, r = -0.997 (p = 0.003). K(s) of fibrin gels obtained
      from purified systems with fibrinogen incubated with homocysteine was (7.07 +/-
      0.27) * 10(-9) cm(2), control was (11.40 +/- 0.37) * 10(-9) cm(2) (n = 3; p <
      0.01). K(s) of fibrin gels obtained with factor XIII treated with homocysteine
      was (1.47 +/- 0.17) * 10(-9) cm (2), and control was (3.31 +/- 0.31) * 10(-9)
      cm(2) (n = 3; p<0.01). Plasma incubated with high homocysteine concentrations
      produced fibrin clots significantly less permeable than controls in a dose
      dependent manner, and the results showed that fibrinogen and factor XIII were
      involved in that detrimental effect. These findings might explain the impaired
      fibrinolysis related to increased homocysteine levels and contribute to
      understanding the association between the amino acid and thrombosis.

PMID- 19744702
TI  - Albumin precursor and Hsp70 modulate corneal wound healing in an organ culture
      model.
AB  - In order to investigate the role of albumin precursor and Hsp70 in corneal wound
      healing, we have analyzed the distribution of these proteins in wounded and non
      wounded corneas of rabbits and the effects of topical applications of anti
      albumin precursor and anti-Hsp70 antibodies on wound healing. Anti-albumin
      precursor and anti-Hsp70 antibodies were topically applied in healing corneal
      epithelium of rabbit eyes in organ culture. Corneas were allowed to heal in vitro
      for up to 120 h in serum-free medium with 5 and 10 MUg/ml or without (migrating
      control) anti-albumin precursor/ or anti-Hsp70 antibodies. Fibronectin (Fb) (5
      MUg/ml) was used as a positive control. Immunofluorescence labelling was used to
      detect proteins in corneal epithelium at various time intervals following an
      epithelial defect. Delay in wound healing (p<0.005) was observed with 10 MUg/ml
      anti-albumin antibody labelling. A similar pattern was observed when anti
      fibronectin antibody (5 MUg/ml) alone and in combination with anti-albumin (10
      MUg/ml) was ectopically added with wound closure occurring at 120 h. However with
      anti-Hsp70 antibody (5 MUg/ml) slightly delayed (p<0.005) wound closure was
      observed at 96 h and considerable retardation >120 h with 10 MUg/ml.
      Additionally, immunofluoresence showed a strong co-localization of Hsp70 and
      albumin precursor during the active phase of wound healing. The presence of
      albumin precursor and Hsp70 in the epithelial compartment of the cornea indicates
      a role for these proteins in modulating cell behavior such as epithelial growth,
      adhesion or regeneration, thus contributing to corneal epithelial wound healing.

PMID- 19744703
TI  - The detection of cervical intraepithelial neoplasia by electrical impedance
      spectroscopy: the effects of acetic acid and tissue homogeneity.
AB  - OBJECTIVE: To evaluate the efficacy of an electrical impedance probe
      (Epitheliometer) in the diagnosis of high grade cervical intraepithelial
      neoplasia (CIN) in women referred with cervical smear abnormalities and to assess
      the effect of acetic acid (AA) and tissue boundaries on the measurements.
      METHODS: A prospective observational study was undertaken in the colposcopy
      clinic. One hundred and sixty-five women, either with a clinical indication or
      abnormal cervical cytology, were recruited into the study. A pencil type probe
      was used to record impedance spectra from 12 points on the cervix before and
      after the application of 5% AA. Spectra were also recorded from tissue
      boundaries. Colposcopic examinations, including probe positioning, were video
      recorded to allow for correlations between histopathological diagnosis of
      colposcopically directed biopsies, colposcopic impression and the diagnosis based
      on impedance measurements. RESULTS: Receiver operating characteristic (ROC)
      curves were derived. The areas under the curves (AUCs) to discriminate original
      squamous from high grade CIN were 0.80 (pre AA) and 0.79 (post AA). Comparison of
      these curves showed no significant difference, indicating that application of AA
      does not produce a large change in spectra. The probe could distinguish tissue
      boundaries from homogeneous tissue points. CONCLUSION: The Epitheliometer has the
      potential to be used as an adjunct to colposcopy in the diagnosis of high grade
      CIN. It has the advantage of real time results, decreasing the need for
      diagnostic cervical biopsies, and facilitates a wider use of the 'see and treat'
      policy without the risk of overtreatment.

PMID- 19744704
TI  - Differing sperm ability to penetrate the oocyte in vivo and in vitro as revealed
      using colloidal preparations.
AB  - The penetration ability of boar (Sus scrofa domestica) spermatozoa exposed to
      viscous preparations under in vivo and in vitro fertilization conditions has been
      examined. Experiments involving induced ovulation in prepubertal animals and
      surgical insemination directly into the oviduct isthmus revealed an advantage of
      colloidal preparations. Based on within-animal comparisons, the incidence of
      penetration was 100% using both spermatozoa suspended in a viscous preparation of
      plant extracts and spermatozoa suspended in a control medium. However,
      percentages of monospermy were 22.2% in 54 oocytes inseminated with the control
      suspension compared with 62.5% in 48 oocytes inseminated with the colloidal
      preparation. An in vitro study involving 355 oocytes from slaughterhouse ovaries
      inseminated with in vitro-capacitated spermatozoa gave similar percentages of
      penetrated oocytes for both the control and colloidal suspensions. In this case,
      however, the percentage of monospermy was 32.7% in the control group compared
      with 10.6% for spermatozoa suspended in the colloidal preparation. Higher mean
      numbers of sperm inside the oocytes and higher numbers of sperm bound to the zona
      pellucida were also observed with the colloidal suspensions. In vitro motility
      and viability for spermatozoa in the colloidal suspensions were enhanced compared
      with that of the control group. Lower sperm membrane lipid disorder and reactive
      oxygen species generation were also observed in the viscous solution. These
      findings suggest that viscous fluids can enhance the ability of sperm to move,
      bind, and penetrate the oocyte in vitro, although this influence may be masked in
      vivo due to the already high viscosity in the oviductal fluid close to the time
      of ovulation.

PMID- 19744705
TI  - Effect of filler particle size and morphology on force/work parameters for
      stickiness of unset resin-composites.
AB  - OBJECTIVES: To investigate the effect of variation in filler particle size and
      morphology within an unset model series of resin-composites on two stickiness
      parameters: (1) maximum probe separation-force and (2) work-of-separation. This
      study was to complement previously reported measurements of composite stickiness
      in terms of a strain-parameter, 'peak-height'. MATERIALS AND METHODS: Eleven
      experimental light cured resin-composites were selected. All had the same matrix
      (Bis-GMA, UDMA and TEGDMA, with 0.33% camphoroquinone) and the same filler volume
      fraction-56.7%, however filler particles varied in size and shape and were either
      unimodal or multimodal in size-distribution. Each material was placed in a
      cylindrical mould (phi=7mmx5mm depth) held at 26 or 37 degrees C. The maximum
      force (F(max), N) and work of probe-separation (W(s), Nmm) were measured. A flat
      ended stainless-steel probe (phi=6mm) was mechanically lowered onto and into the
      surface of the unset sample, until a compressive force of 1N was reached, which
      was held constant for 1s. Then the probe was moved vertically upward at a
      constant speed; either 2 or 8mm/s. The tensile force produced on the probe by the
      sticky composite was plotted against displacement and the maximum value was
      identified (F(max)). W(s) was obtained as the integrated area. Data was analyzed
      by multivariate ANOVA and multiple pair-wise comparisons using a Tukey post hoc
      test to establish homogenous subsets (at p=0.05) for F(max) and a Games-Howell
      was used for W(s). RESULTS: As potential measures of stickiness, F(max) and W(s)
      showed more coherent trends with fillersize when measured at the lower of the two
      probe speeds, 2mm/s. For unimodal resin-composite F(max) ranged from 1.04 to
      5.11N and W(s) from 0.48 to 11.12Nmm. For the multimodal resin-composite they
      ranged from 1.64 to 4.13N and from 2.32 to 8.34Nmm respectively. Temperature
      increase tended to slightly reduce F(max), although this trend was not
      consistent. W(s) generally increased with temperature. CONCLUSION: Filler
      particle size and morphology influences F(max) and W(s) of uncured resin
      composite which partly express the handling behaviors of resin-composites.

PMID- 19744706
TI  - Clonal relationship between precursor B-cell acute lymphoblastic leukemia and
      histiocytic sarcoma: a case report and discussion in the context of similar
      cases.

PMID- 19744707
TI  - Determination of imatinib plasma levels in patients with chronic myeloid leukemia
      by high performance liquid chromatography-ultraviolet detection and liquid
      chromatography-tandem mass spectrometry: methods' comparison.
AB  - The aims of this study were to validate and compare HPLC and LCMSMS analytical
      methods and their applicability for the quantitation of imatinib in human plasma.
      A total of 50 patients with chronic myeloid leukemia (CML) in chronic phase (CP)
      receiving 400 mg/day imatinib were enrolled in the study. Drug levels were
      determined by HPLC-UV and LCMSMS. HPLC intra-day accuracy ranged from 100.51 to
      103.19%. LCMSMS accuracy ranged from 89.72 to 106.29%. The correlation
      coefficient between both methods was r(2)=0.96. HPLC can be used for imatinib
      levels' determinations in patients accurately and precisely.

PMID- 19744708
TI  - Refractory anaemia with ring sideroblasts associated with marked thrombocytosis
      (RARS-T) and JAK2(V617F) mutation transformed to acute myeloid leukaemia with
      chromosomal evolution including monosomy 7.

PMID- 19744709
TI  - Non-therapy-related acute lymphoblastic leukemia with t(9;22)(q34;q11) as a
      second malignancy: report of a case and review of the literature.

PMID- 19744710
TI  - Low-dose cytarabine and aclarubicin in combination with granulocyte colony
      stimulating factor for elderly patients with previously untreated acute myeloid
      leukemia.
AB  - We evaluated the efficacy of low-dose cytarabine and aclarubicin combined with
      granulocyte colony-stimulating factor (CAG) in elderly patients with previously
      untreated acute myeloid leukemia. Patients aged between 60 and 70 years who were
      not eligible for standard chemotherapy protocols and patients aged over 70 years
      were all registered. Thirty-three of 68 patients (49%) achieved remission. Median
      disease-free survival was 10 months and overall survival was nine months.
      Performance status after chemotherapy in patients who achieved remission was
      generally favorable. The present study demonstrates that CAG therapy is
      efficacious and well tolerated in the majority of elderly patients.

PMID- 19744711
TI  - Mutagenicity assessment in a river basin influenced by agricultural, urban and
      industrial sources.
AB  - The genotoxic potential of samples from a river basin under impact of
      agricultural, urban and industrial activities was studied, to investigate the
      influence of climatic variations on the mutagenicity. Three sites were analyzed,
      a reference-SI121-and two with strong anthropic influence-SI028 and SI008. The
      Salmonella/microsome assay was performed in the presence/absence of hepatic
      metabolic system in samples of water and organic extracts. Different strains were
      used to identify frameshift mutagens, base-pair substitutions and oxidative
      damage. Indicative mutagens were detected especially with metabolization. The
      toxic response, which was quite frequent, may have interfered in the mutagenicity
      detection. The adverse impact of anthropic activities was detected through
      recurring cytotoxic and mutagenic responses at the site of greater urban and
      industrial concentration. The data suggest the influence of climatic conditions
      on mutagenic response, reinforcing the need to investigate mutagenicity for a
      prolonged period to a better risk assessment of exposure.

PMID- 19744712
TI  - Gender differences in client-provider relationship as active ingredient in
      substance abuse treatment.
AB  - The client-provider relationship is increasingly evaluated as an active
      ingredient in the delivery of substance abuse treatment services. This study
      examines gender differences in client-provider relationship as an important
      treatment ingredient affecting retention in treatment and reduced post-treatment
      substance use. The study uses data collected for the National Treatment
      Improvement Evaluation Study (NTIES), a prospective, cohort study of U.S.
      substance abuse treatment programs and their clients. Data on individual
      characteristics were collected at the pre-treatment interview; on client-provider
      relationship and services received at treatment exit; and on post-treatment drug
      use at 12 months post-treatment. The analytic sample consists of 3027 clients
      from 59 service delivery units (1922 men and 1105 women). Structural equation
      modeling (SEM) was used to assess the structural relations and causal connections
      between relationship and service variables and treatment outcome variables.
      Results indicate that a positive client-provider relationship is related directly
      to longer duration and reduced post-treatment drug use for the total sample and
      for men analyzed separately. For women, a positive client-provider relationship
      was related directly to treatment duration and only indirectly to reduced post
      treatment drug use. The findings point to the significance of including client
      provider relationship in service delivery models--both as a therapeutic element
      as well as an element facilitative of matching services to specific client needs.

PMID- 19744713
TI  - Farmworker children's residential non-dietary exposure estimates from micro-level
      activity time series.
AB  - Farmworkers' children may have increased pesticide exposure through dermal
      absorption and non-dietary ingestion, routes that are difficult to measure and
      model. The Cumulative Aggregate Simulation of Exposure (CASE) model, integrates
      the complexity of human behavior and variability of exposure processes by
      combining micro-level activity time series (MLATS) and mechanistic exposure
      equations. CASE was used to estimate residential non-dietary organophosphate
      pesticide exposure (i.e., inhalation, dermal, and non-dietary ingestion) to
      California farmworker children and evaluate the micro-activity approach. MLATS
      collected from children and distributions developed from pesticide measurements
      in farmworkers' residences served as inputs. While estimated diazinon exposure
      was greater for inhalation, chlorpyrifos exposure was greater for the other
      routes. Greater variability existed between children (sigma(B)(2)=0.22-0.39) than
      within each child's simulations (sigma(W)(2)=0.01-0.02) for dermal and non
      dietary ingestion. Dermal exposure simulations were not significantly different
      than measured values from dosimeters worn by the children. Non-dietary ingestion
      exposure estimates were comparable to duplicate diet measurements, indicating
      this route may contribute substantially to aggregate exposure. The results
      suggest the importance of the micro-activity approach for estimating non-dietary
      exposure. Other methods may underestimate exposure via these routes. Model
      simulations can be used to identify at-risk children and target intervention
      strategies.

PMID- 19744714
TI  - Role of Cybr, a cytohesin binder and regulator, in CD4(+) T-cell function and
      host immunity.
AB  - Cytohesin binder and regulator (Cybr) is known to regulate leukocyte adhesion and
      migration. However, its function in T-cells is poorly understood. Here, we
      investigated the role of Cybr in CD4(+) T-cell function and host immunity. Cybr
      inhibited p38 phosphorylation following CD4(+) T-cell stimulation. Since p38
      regulates the expression of T-box expressed in T-cells (T-bet) but not GATA
      binding protein 3 (GATA-3) in T-cells, Cybr decreased the expression of T-bet and
      IFN-gamma in CD4(+) T-cells. Moreover, we found that host immunity against
      Listeria infection and IFN-gamma production in blood were significantly
      compromised in Cybr-overexpressing transgenic mice. In summary, our data suggest
      that Cybr represses the expression of T-bet and IFN-gamma via an inhibition of
      p38 in T-cells and consequently reduces host resistance to bacterial infection in
      mice.

PMID- 19744715
TI  - Doctor-patient communication in glaucoma care: analysis of videotaped encounters
      in community-based office practice.
AB  - PURPOSE: To assess doctor-patient communication in patients with glaucoma.
      DESIGN: Observational cohort study. PARTICIPANTS: Twenty-three ophthalmologists
      and 50 patients with glaucoma. METHODS: Doctor-patient encounters were audio- and
      videotaped and analyzed using validated sociolinguistic approaches. After the
      visit, the doctor and the patient completed questionnaires, and patients were
      interviewed using a semistructured, patient-centered protocol. MAIN OUTCOME
      MEASURES: Summary statistics about doctor-patient encounters, assessment of
      alignment of attitudes between patients and doctors, and patient admission to
      missing doses. RESULTS: Physicians spent an average of 8.0 (standard deviation
      [SD], 3.1; median, 7.8) minutes in the room with the patient and an average of
      5.8 (SD, 2.4; median, 7.5) minutes talking with the patient, delivering 70% of
      all spoken words and asking two thirds of all questions. Glaucoma-related
      discussion occupied 50% of talk time and was focused primarily on examinations
      and treatment (25%). One third of discussions addressed ocular issues other than
      glaucoma. Virtually all physician questions (94%) were closed ended. Most patient
      questions were about intraocular pressure (20% of visits), details of the
      medication regimen (20%), disease status (14%), and testing (12%). Although
      physicians and patients were aligned in believing that the physician should
      control the visit agenda, physicians tended to support greater physician control
      of decision making than did patients. Physicians failed to identify most patients
      who admitted to missing doses, a surrogate for nonadherence, stating that 10 of
      13 in this category were taking drops "all" or "most" of the time. Physician
      interviews detected 3 of the 11 patients whose postvisit questionnaire indicated
      missing a dose in the last week compared with 11 of the 11 detected by the
      postvisit research interview. Patients who stated they had missed doses recently
      reported being less satisfied with the doctor-patient encounter than those who
      did not. CONCLUSIONS: Doctor-patient dialogue was universally physician centered;
      physicians spoke 70% of the words and asked closed-ended questions that
      restricted the patient's contribution to "yes/no" or brief responses. A minority
      of physicians ever asked patients if they had questions. In contrast with the
      patient-centered research interview, doctors' physician-centered communication
      failed to identify most patients who had missed doses.

PMID- 19744716
TI  - Blindness in a 25-year follow-up of a population-based cohort of Danish type 1
      diabetic patients.
AB  - PURPOSE: To assess the long-term incidence of blindness and to evaluate risk
      factors for blindness in a population-based cohort of type 1 diabetic patients.
      DESIGN: Retrospective cohort study. PARTICIPANTS: A population-based cohort of
      573 type 1 diabetic patients, all of whom participated in a clinical
      ophthalmologic examination in 1981 and 1982 and were followed up for 25 years.
      METHODS: At the baseline examination in 1981 and 1982, visual acuity, level of
      retinopathy, maculopathy, hemoglobin A(1) (HbA(1)), proteinuria, smoking habits,
      and blood pressure were evaluated and related to the subsequent development of
      blindness. Blindness was defined as present in patients who were registered as
      members of the Danish Association of the Blind between baseline and January 2007.
      The Danish Association of the Blind is a voluntary organization open for all
      patients with a best-corrected visual acuity in the best eye of <or=6/60 (20/200)
      or with complications (i.e., visual fields <10 degrees ) subjectively leading to
      a best-corrected visual acuity in the best eye of <or=6/60 (20/200). MAIN OUTCOME
      MEASURES: Evaluation of 25-year incidence of blindness, predictors for blindness,
      and gender-specific incidence rates for blindness. RESULTS: The 25-year
      cumulative crude incidence of blindness was 7.5% (men, 8.0%; women, 6.8%; P =
      0.61), corresponding to a mortality-adjusted cumulative incidence of blindness of
      9.5% (95% confidence interval [CI], 7.1%-12.0%) and an overall incidence rate of
      blindness of 4.11 per 1000 person-years (95% CI, 3.03-5.59 per 1000 person
      years). Blindness was predicted by HbA(1) and maculopathy at baseline. The odds
      ratio of blindness during follow-up was 1.69 (95% CI, 1.01-2.84) for a 1%
      increase in baseline HbA(1) and was 6.18 (95% CI, 1.18-32.47) and 8.61 (95% CI,
      2.54-29.23) for patients with maculopathy in combination with nonproliferative
      retinopathy and proliferative retinopathy, respectively. Age and duration at
      baseline, gender, proteinuria, smoking, systolic and diastolic blood pressure,
      and visual acuity at baseline were not associated with the development of
      blindness. Mortality was higher in patients who had become blind (61.0% vs.
      42.1%; P = 0.02). CONCLUSIONS: Blindness is still a common complication in type 1
      diabetes. Glycemic regulation and the presence of maculopathy are important risk
      factors for the development of blindness.

PMID- 19744717
TI  - Complete local elimination of infectious trachoma from severely affected
      communities after six biannual mass azithromycin distributions.
AB  - OBJECTIVE: To determine whether infectious trachoma can be completely eliminated
      from severely affected villages. DESIGN: Cross-sectional survey of 2 villages
      previously enrolled and monitored over 42 months as part of a larger, group
      randomized clinical trial. PARTICIPANTS: A total of 758 individuals residing in 2
      villages with high baseline trachoma prevalence, of a total population of 768
      (98.7%). METHODS: All members of the 2 villages were offered 6 biannual mass
      treatments with oral azithromycin. At 42 months, each current village member was
      examined. The right upper tarsal conjunctiva was everted and swabbed. Samples
      were processed for evidence of Chlamydia trachomatis RNA. MAIN OUTCOME MEASURES:
      Clinical activity by World Health Organization simplified grading scale for
      trachoma and laboratory evidence of chlamydial RNA. RESULTS: Average antibiotic
      coverage over the study period was 90% and 94% in the 2 villages. Clinical
      trachoma activity in children aged 1 to 5 years decreased from 78% and 83% in the
      2 villages before treatment to 17% and 24% at 42 months. Polymerase chain
      reaction (PCR) evidence of infection in the same age group decreased from 48% to
      0% in both villages at 42 months. When all age groups were examined, there were
      zero cases with evidence of chlamydial RNA among 758 total villagers tested.
      CONCLUSIONS: Biannual mass distribution of azithromycin can locally eliminate
      ocular chlamydial infection from severely affected communities.

PMID- 19744718
TI  - Proposed diagnostic criteria for obstructive meibomian gland dysfunction.
AB  - PURPOSE: To compare clinical findings between patients with obstructive meibomian
      gland dysfunction (MGD) and normal controls and to propose diagnostic criteria
      for obstructive MGD. DESIGN: Cross-sectional, observational case series.
      PARTICIPANTS: Fifty-three eyes of 53 patients (18 men, 35 women; age [mean +/-
      standard deviation] 71.4 +/- 10.0 years) who were diagnosed with obstructive MGD
      and 60 eyes of 60 healthy volunteers (22 men, 38 women; 71.0 +/- 9.3 years) as a
      control group. METHODS: Ocular symptoms were scored from 0 to 14 according to the
      number of existing symptoms. Lid margin abnormality was scored from 0 to 4
      depending on the number of existing abnormalities. Meibomian gland changes were
      scored from 0 to 6 based on noncontact meibography (meibo-score). Superficial
      punctuate keratopathy (SPK) was scored from 0 to 3. Meibum was graded from 0 to 3
      depending on the volume and quality. Tear film production was evaluated by
      Schirmer's test. Receiver operating characteristic curves with calculations of
      area under the curve (AUC) were used to describe the accuracy of each parameter
      to differentiate obstructive MGD from normal eyes. MAIN OUTCOME MEASURES: Ocular
      symptom score, lid margin abnormality score, meibo-score, meibum score, SPK
      score, tear film breakup time (BUT), and the Schirmer value. RESULTS: Ocular
      symptom score, lid margin abnormality score, meibo-score, meibum score, and SPK
      score were significantly higher in the obstructive MGD group than in the control
      group (P<0.0001 for all scores). The BUT was significantly shorter in the
      obstructive MGD group than in the control group (P<0.0001). The AUC values
      indicated that the ocular symptom score had the highest diagnostic power as a
      single parameter, followed by the lid margin abnormality score, meibo-score, and
      BUT. CONCLUSIONS: Based on these findings, we recommend that physicians use the
      ocular symptom score, lid margin abnormality score, and meibo-score to diagnose
      MGD. Obstructive MGD should be suspected when any 2 of the 3 scores are abnormal.
      Obstructive MGD is very likely when all 3 scores are abnormal.

PMID- 19744719
TI  - Average 3-dimensional models for the comparison of Orbscan II and Pentacam
      pachymetry maps in normal corneas.
AB  - PURPOSE: To assess the reliability of Orbscan (Bausch & Lomb, Salt Lake City, UT)
      and Pentacam (Oculus, Wetzlar, Germany) central corneal thickness (CCT) and
      peripheral corneal thickness (PCT) measurements based on 2 methodologies. DESIGN:
      Evaluation of a diagnostic technology. PARTICIPANTS: Thirty healthy volunteers
      were recruited prospectively at the Department of Ophthalmology of the Hotel-Dieu
      Hospital, Paris, France. METHODS: Central corneal thickness and PCT were
      assessed, using ultrasound pachymetry (USP) as the gold standard. Two
      methodologies were used: (1) the traditional analysis of pachymetry data from 1
      central and 8 peripheral reference positions on the cornea, and (2) a 3
      dimensional (3-D) analysis based on average corneal pachymetry maps constructed
      for each system (Orbscan, Pentacam, and USP), each operator (operators 1 and 2),
      and each visit (visits A and B). MAIN OUTCOME MEASURES: Repeatability,
      intersystem reproducibility, interoperator reproducibility, reproducibility over
      time, and accuracy of Orbscan and Pentacam CCT and PCT measurements. Distribution
      and statistical significance of the differences between 3-D average maps.
      RESULTS: Repeatability (Orbscan intraclass correlation coefficients [ICCs], 0.967
      0.992; Pentacam ICCs, 0.986-0.997), interoperator reproducibility, and
      reproducibility over time (ICCs, 0.976-0.997) were excellent to almost perfect
      for both systems. Intersystem agreement was almost perfect for CCT (ICC, 0.980),
      but less strong for PCT (ICCs, 0.928-0.979). Despite a good to excellent
      agreement between the optical systems and USP (ICCs, 0.608-0.958), USP CCT
      readings were thicker (mean difference, up to 15.2 microm; P<0.05), and USP PCT
      readings were thinner (P<0.05). Orbscan and Pentacam average maps allowed
      comprehensive interpretation of differences between populations according to the
      magnitude, distribution, and statistical significance, minimizing the risk of
      giving excessive weight to few data measured at specific locations on the cornea.
      CONCLUSIONS: Both methodologies showed that Orbscan and Pentacam CCT readings are
      interchangeable, whereas caution should be used for PCT readings.
      Interchangeability with USP measurements also was shown to be limited. The high
      repeatability, interoperator reproducibility, reproducibility over time, the
      extent of the information generated by a single capture, and the noncontact
      nature of the Orbscan and Pentacam all suggest that optical systems eventually
      may replace USP as the gold standard for corneal pachymetry.

PMID- 19744720
TI  - Comparison and evaluation of ocular biometry using a new noncontact optical low
      coherence reflectometer.
AB  - PURPOSE: To evaluate a new high-resolution noncontact biometer (Lenstar; Haag
      Streit AG, Koeniz, Switzerland) using optical low-coherence reflectometry and to
      compare the clinical measurements with those obtained from the IOLMaster (Carl
      Zeiss, Jena, Germany) and the Pachmumeter (Haag-Streit AG). DESIGN: Exploratory
      evaluation of diagnostic technology and nonrandomized, prospective clinical
      trial. PARTICIPANTS: Eighty subjects (144 eyes) aged 20 to 90 years with
      cataractous, pseudophakic, aphakic, silicon oil-filled, or normal eyes. METHODS:
      Measurements of axial length (AL), anterior chamber depth (ACD), central corneal
      thickness (CCT), corneal radius (R1 [flattest radius of corneal curvature] and R2
      [steep radius, 90 degrees apart from R1]), and axis of the flattest radius (Ax1)
      obtained with the Lenstar were compared with those obtained with the IOLMaster or
      Pachmumeter. The results were evaluated using Bland-Altman analyses. The
      differences between both methods were assessed using the paired t test, and its
      correlation was evaluated by Pearson coefficient. MAIN OUTCOME MEASURES: Axial
      length, CCT, ACD, R1, R2, and Ax1. RESULTS: The overall mean AL measured with the
      Lenstar and the IOLMaster was 24.1 mm (r = 0.999). Anterior chamber depth was
      3.19 mm (Lenstar) and 3.17 mm (IOLMaster; r = 0.875). Excellent correlations also
      were found for the corneal radius and the axis of flattest radius (R1, r = 0.927;
      R2, r = 0.929; and Ax1, r = 0.938). Mean CCT was 0.557 mm (r = 0.978) for both
      Lenstar and Pachmumeter. CONCLUSIONS: Measurements with the new Lenstar
      correlated well with those with the IOLMaster and Pachmumeter in cataractous,
      pseudophakic, aphakic, silicon oil-filled, and normal eyes. It is an accurate,
      fast instrument that provides additional information of interest to any cataract
      or refractive surgeon.

PMID- 19744721
TI  - Prognostic significance of delayed structural recovery after macular hole
      surgery.
AB  - PURPOSE: To assess the prognostic significance for visual function of persistent
      subfoveal fluid and persistent photoreceptor layer discontinuity in eyes in which
      hole closure had been obtained 3 months after macular hole surgery. DESIGN:
      Ancillary study of subjects enrolled in a randomized clinical trial.
      PARTICIPANTS: Participants were recruited from a randomized clinical trial
      evaluating internal limiting membrane (ILM) peeling in macular hole surgery. The
      study included 74 eyes in which a contiguous retinal surface or a full attachment
      with a flat neuroretinal rim had been reestablished after macular hole surgery.
      METHODS: Contrast-enhanced optical coherence tomography was used to detect
      closure defects involving substrata of the retina with particular emphasis on the
      photoreceptor layer. Outcomes were compared with best-corrected visual acuity
      (BCVA) 12 months after surgery. MAIN OUTCOME MEASURES: Postoperative foveal
      configuration and foveal photoreceptor layer discontinuity diameter 3 months
      after macular hole surgery. RESULTS: Persistent subfoveal fluid 3 months after
      macular hole surgery, which was found in 36.5% of eyes, was not associated with a
      significantly different BCVA after 12 months compared with eyes with a fully
      attached fovea at 3 months (70.9 letters vs. 72.0 letters; P = 0.59). Receiver
      operating characteristics curve analysis identified persistent photoreceptor
      layer discontinuity of a diameter of more than 1477 microm after 3 months to be
      associated with poorer BCVA after 12 months (P<0.001), yet an overall reduction
      in discontinuity diameter from 3 to 12 months (P<0.001) was not correlated with a
      concurrent improvement in BCVA (r = -0.040; P = 0.81). Persistence of fluid and
      diameter of discontinuity at 3 months were not related to whether ILM peeling was
      used; however, secondary macular hole surgery had a significant influence on
      diameter of photoreceptor layer discontinuity at 3 months. CONCLUSIONS:
      Structural recovery in the form of photoreceptor layer discontinuity with a
      diameter of more than approximately 1500 microm 3 months after macular hole
      surgery was associated with poorer visual acuity after 12 months than less
      extensive discontinuity. Subfoveal fluid persisting after 3 months had
      disappeared after 12 months in all but 5 of 74 eyes and had no effect on final
      visual outcome.

PMID- 19744722
TI  - Cilial entropion: surgical outcome with a new modification of the Hotz procedure.
AB  - PURPOSE: To report the surgical outcome with a new modification of the Hotz
      procedure for cilial entropion repair. DESIGN: Retrospective case series.
      PARTICIPANTS: Forty-nine lower eyelids of 29 patients (22 female, 7 male; average
      age 8.4 years, range 2-27 years). METHODS: The study included all patients
      diagnosed with cilial entropion and significant ocular irritation causing
      epiphora, photophobia, and ocular discharge, with or without keratitis. Surgery
      is based on dividing the anterior layer of the lower eyelid retractors from the
      anterior tarsal plate surface, definite identification of the inferior tarsal
      plate border, and reinforcement of the skin to the tarsal plate and lower eyelid
      retractors. Surgical outcome was defined as "good" or "fair" when there was no
      contact between the eyelashes and the globe or when less than 5 asymptomatic
      eyelashes had direct contact with the globe, respectively. A "poor" outcome was
      defined as either the majority of eyelashes remained in contact with the globe or
      persistence of irritation/keratitis in the presence of residual in-turned
      eyelashes. A successful outcome ("good" or "fair") required no additional
      surgical intervention. MAIN OUTCOME MEASURES: Surgical outcome ("good," "fair,"
      or "poor"), postoperative complications, recurrence. RESULTS: During a mean
      follow-up period of 27.4 months (range, 3-50 months), 40 eyelids (82%) were
      judged postoperatively as "good," 7 eyelids (14%) were judged as "fair," and 2
      eyelids (4%) were judged as "poor." The 2 eyelids with a poor outcome were
      reoperated successfully using the same technique. No postoperative complications
      were recorded. There were no cases of recurrence, except the 2 eyelids with a
      "poor" outcome, during the follow-up period. CONCLUSIONS: Our modification of the
      Hotz procedure is based on identifying and dividing the anterior layer of the
      lower eyelid retractors and reinforcing the skin to the lower border of the
      inferior tarsal plate and lower eyelid retractors. This is a useful and
      predictive technique for cilial entropion repair and results in a high success
      rate.

PMID- 19744723
TI  - Association of retinal sensitivity and morphology during antiangiogenic treatment
      of retinal vein occlusion over one year.
AB  - PURPOSE: Evaluation of the association between functional and anatomic retinal
      changes during anti-vascular endothelial growth factor (VEGF) therapy with
      bevacizumab (Avastin) in patients with cystoid macular edema secondary to retinal
      vein occlusion (RVO) using microperimetry and spectral domain optical coherence
      tomography (SD-OCT). DESIGN: Prospective, uncontrolled study (EUDRACT NR-2005
      003288-21). PARTICIPANTS: Twenty-eight patients with cystoid macular edema
      secondary to RVO. METHODS: Patients initially received 3 consecutive intravitreal
      injections of 1.25 mg bevacizumab at 4-week intervals. Further treatment was
      based on morphologic (OCT) and functional best-corrected visual acuity (BCVA)
      findings. During the 1-year follow-up, a rigorous standardized evaluation was
      performed monthly. Macular function was documented by microperimetry (Nidek, MP1
      Microperimeter) and BCVA based on the Early Treatment in Diabetic Retinopathy
      Study (ETDRS). Morphologic parameters included central retinal thickness (CRT) as
      measured by conventional OCT (Stratus), and central subfield thickness (CST),
      mean retinal thickness (MRT), and retinal volume (RV) measured by SD-OCT. MAIN
      OUTCOME MEASURES: Imaging of retinal morphology using OCT and SD-OCT and
      evaluation of retinal function assessed with microperimetry and ETDRS charts
      during 12 months of anti-VEGF treatment. RESULTS: Within 6 months, the mean area
      of absolute scotoma was reduced from 21.4% of the central visual field to 6.4%
      and remained at this level until month 12 (7.4%). Mean BCVA improved from 51 to
      66 letters on ETDRS charts. The CRT, CST, and MRT decreased significantly
      (P<0.002) and remained stable during the follow-up. The RV values did not improve
      significantly under therapy. Statistical analysis using a linear effects model
      revealed significant associations between the functional and morphologic
      outcomes, most notably between BCVA, macular sensitivity, CRT (Stratus OCT), CST,
      and MRT (Cirrus OCT) values. CONCLUSIONS: Central retinal morphology, especially
      CRT and CST measured by conventional and SD-OCT, and retinal function improved
      significantly during treatment of RVO with a flexible dosing regimen of
      intravitreal bevacizumab. Functional (central visual acuity and visual field) and
      morphologic parameters (retinal thickness) were significantly related. These
      associations highlight the value of OCT imaging for assessing this disease
      entity.

PMID- 19744724
TI  - Congenital toxoplasmosis in southeastern Brazil: results of early ophthalmologic
      examination of a large cohort of neonates.
AB  - OBJECTIVE: To report results of early ophthalmologic examinations in a large
      cohort of newborns with congenital toxoplasmosis (CT) after neonatal screening.
      DESIGN: Cross-sectional analysis of a cohort. PARTICIPANTS: A total of 178
      newborns with confirmed CT from 146,307 screened babies (95% of live births) from
      Minas Gerais state, southeastern Brazil. METHODS: From November 2006 to May 2007,
      newborns underwent neonatal screening by immunoglobulin (Ig)M capture of dried
      blood samples. On all positive or suspected cases, confirmative serology was
      performed on babies and their mothers. Congenital toxoplasmosis was confirmed in
      newborns who had IgM and/or IgA and IgG, or IgG associated with suggestive ocular
      lesions (with IgM and IgG in the mother). Ophthalmologic evaluation consisted of
      indirect ophthalmoscopy with a lid speculum. Pediatric examination and radiologic
      studies of the central nervous system were also performed. In selected cases,
      biomicroscopy of the anterior segment, fundus photographs, or ultrasonography (B
      scan) was performed. MAIN OUTCOME MEASURES: Prevalence of retinochoroidal
      lesions, either cicatricial or active, and their location and associated
      findings, such as vascular sheathing, hemorrhage, vitreous opacities, and retinal
      detachment, were evaluated. The occurrence of cataract, microphthalmia,
      microcephaly, intracranial calcification, and hydrocephalus was also recorded.
      RESULTS: Of 146,307 neonates screened, 190 had CT, yielding a prevalence of 1 in
      770 live births, of whom 178 (93.7%) underwent standardized ophthalmologic
      examination at an average age of 55.6+/-16.6 days. Of these 178 infants, 142
      (79.8%) had retinochoroidal lesions consistent with CT in at least 1 eye.
      Bilateral involvement was noted in 113 patients (63.5%). Macular involvement was
      seen in 165 eyes (46.3%) of 111 patients (62.4%). Active lesions were observed in
      142 eyes (39.9%) of 85 patients (47.8%). These lesions were located in the macula
      of 75 eyes (21.1%) and were associated with retinal vascular sheathing in 44 eyes
      (12.4%). CONCLUSIONS: A high prevalence of CT was encountered (1/770) with high
      rates of early retinochoroidal involvement ( approximately 80%) and many active
      lesions (in approximately 50%), indicating a possibly more severe ocular
      involvement by CT in Brazil than in other parts of the world. The hypotheses of
      higher parasite virulence and increased individual susceptibility are being
      currently investigated.

PMID- 19744725
TI  - Adjuvant interferon therapy for patients with uveal melanoma at high risk of
      metastasis.
AB  - PURPOSE: To examine whether interferon (IFN)-alfa-2a treatment after radiation or
      enucleation reduces death rates in patients with uveal melanoma. DESIGN:
      Interventional, comparative case series. PARTICIPANTS: Subjects were identified
      through the ocular oncology clinic of the Massachusetts Eye and Ear Infirmary.
      Patients eligible for the study were at increased risk of metastasis because of
      the presence of at least one of the following characteristics: age >or=65 years,
      largest tumor diameter (LTD) >or=15 mm, ciliary body involvement of the tumor, or
      extrascleral tumor extension. METHODS: Between May 1995 and June 1999, 121
      patients with choroidal or ciliary body melanoma began a 2-year course of therapy
      (3 MIU IFN-alfa-2a subcutaneously 3 times per week), initiated within 3 years of
      primary therapy. All patients underwent regular monitoring for drug toxicity. To
      evaluate IFN-alfa-2a efficacy, we selected a series of historical controls
      frequency-matched (2:1) to IFN-alfa-2a-treated patients on age (+/-5 years), LTD
      (+/-3 mm), gender, and survival time between primary therapy and initiation of
      IFN therapy. Survival status was ascertained for all patients through December
      2006. MAIN OUTCOME MEASURES: Melanoma-related mortality, metastasis, IFN-related
      toxicities. RESULTS: Fifty-five patients (45%) completed therapy; the median dose
      for IFN-alfa-2a-treated patients was 792 MIU (85% of the theoretic dose). The
      median follow-up time in the IFN-alfa-2a-treated group was approximately 9 years.
      Treatment and control groups were similar with respect to age (P = 0.78), LTD (P
      = 0.38), and gender (P = 1.0). Of 363 patients, 108 developed metastasis under
      observation; 42 of these were IFN-alfa-2a-treated patients. Cumulative 5-year
      melanoma-related death rates were 17% in the radiation or enucleation-only group,
      15% in those who completed the entire IFN-alfa-2a course, and 35% in those who
      discontinued IFN-alfa-2a therapy. In multivariate Cox regression, IFN-alfa-2a had
      no significant influence on melanoma-related mortality (rate ratio = 1.02, 95%
      confidence interval, 0.68-1.5, P = 0.91) or all-cause mortality (rate ratio =
      0.84, 95% confidence interval, 0.58-1.2, P = 0.34). CONCLUSIONS: Interferon-alfa
      2a has no material influence on survival in patients with choroidal melanoma.

PMID- 19744726
TI  - Detection of macular ganglion cell loss in glaucoma by Fourier-domain optical
      coherence tomography.
AB  - PURPOSE: To map ganglion cell complex (GCC) thickness with high-speed Fourier
      domain optical coherence tomography (FD-OCT) and compute novel macular parameters
      for glaucoma diagnosis. DESIGN: Observational, cross-sectional study.
      PARTICIPANTS: One hundred seventy-eight participants in the Advanced Imaging for
      Glaucoma Study, divided into 3 groups: 65 persons in the normal group, 78 in the
      perimetric glaucoma group (PG), and 52 in the preperimetric glaucoma group (PPG).
      METHODS: The RTVue FD-OCT system was used to map the macula over a 7 x 6 mm
      region. The macular OCT images were exported for automatic segmentation using
      software we developed. The program measured macular retinal (MR) thickness and
      GCC thickness. The GCC was defined as the combination of nerve fiber, ganglion
      cell, and inner plexiform layers. Pattern analysis was applied to the GCC map and
      the diagnostic powers of pattern-based diagnostic parameters were investigated.
      Results were compared with time-domain (TD) Stratus OCT measurements of MR and
      circumpapillary nerve fiber layer (NFL) thickness. MAIN OUTCOME MEASURES:
      Repeatability was assessed by intraclass correlation, pooled standard deviation,
      and coefficient of variation. Diagnostic power was assessed by the area under the
      receiver operator characteristic (AROC) curve. Measurements in the PG group were
      the primary measures of performance. RESULTS: The FD-OCT measurements of MR and
      GCC averages had significantly better repeatability than TD-OCT measurements of
      MR and NFL averages. The FD-OCT GCC average had significantly (P = 0.02) higher
      diagnostic power (AROC = 0.90) than MR (AROC = 0.85 for both FD-OCT and TD-OCT)
      in differentiating between PG and normal. One GCC pattern parameter, global loss
      volume, had significantly higher AROC (0.92) than the overall average (P = 0.01).
      The diagnostic powers of the best GCC parameters were statistically equal to TD
      OCT NFL average. CONCLUSIONS: The higher speed and resolution of FD-OCT improved
      the repeatability of macular imaging compared with standard TD-OCT. Ganglion cell
      mapping and pattern analysis improved diagnostic power. The improved diagnostic
      power of macular GCC imaging is on par with, and complementary to, peripapillary
      NFL imaging. Macular imaging with FD-OCT is a useful method for glaucoma
      diagnosis and has potential for tracking glaucoma progression.

PMID- 19744727
TI  - Toric Implantable Collamer Lens for high myopic astigmatic Asian eyes.
AB  - PURPOSE: To evaluate early visual outcomes, refractive outcomes, and
      complications of the Toric Implantable Collamer Lens (TICL) for the correction of
      high myopic astigmatism in Asian eyes. DESIGN: Prospective, nonrandomized
      clinical study. PARTICIPANTS: Forty-four eyes of 29 patients with myopia
      (spherical equivalent) between 6 and 18.25 diopters (D), and 1 and 4.5 D of
      astigmatism. METHODS: Implantation of TICL. MAIN OUTCOME MEASURES: Uncorrected
      visual acuity (UCVA), manifest refraction, best spectacle-corrected visual acuity
      (BSCVA), and postoperative complications. RESULTS: At 6 months postoperatively,
      70.59% of eyes had 20/20 or better UCVA and 68.57% had postoperative UCVA better
      than or equal to preoperative BSCVA. At baseline, no eyes had refractive cylinder
      <1 D; however, postoperatively 77.14% of eyes had <1.00 D of refractive cylinder.
      The mean refractive cylinder changed from 2.64 D (+/-0.91) preoperatively to 0.59
      D (+/-0.51) postoperatively. Sixty percent of eyes were within 0.50 D and 85.71%
      of eyes were within 1.00 D of the targeted cylinder correction. Baseline manifest
      refraction spherical equivalent (MRSE) changed from -13.18 D (+/-2.41) to 0.00 D
      (+/-0.42) postoperatively. The number of eyes within 0.50 D and 1.00 D of the
      predicted MRSE were 82.86% and 97.14%, respectively. A BSCVA of 20/15 occurred in
      45.71% of eyes postoperatively compared with 22.86% of eyes preoperatively. A
      BSCVA of 20/20 or better occurred in 94.29% postoperatively compared with 77.14%
      preoperatively. Postoperatively, 1 eye (2.86%) lost 1 line of BSCVA and none lost
      >1 line of BSCVA. Thirty-one percent of eyes gained 1 line of BSCVA and 8.57%
      gained 2 lines of BSCVA postoperatively. Misalignment of TICL axis occurred in 2
      eyes of 2 patients. CONCLUSIONS: The visual outcomes, refractive outcomes, and
      predictability are comparable with the United States Food and Drug Administration
      data on TICLs in non-Asian eyes. Safety concerns were not identified.

PMID- 19744728
TI  - Refractive errors in a rural Chinese adult population the Handan eye study.
AB  - PURPOSE: To describe the prevalence of and risk factors for myopia and other
      refractive errors in a rural, adult, Chinese population. DESIGN: Population
      based, cross-sectional study. PARTICIPANTS: A clustered, random sampling
      procedure was used to select 7557 Chinese people aged >or=30 years from Handan,
      China. METHODS: All eligible subjects were invited to undergo a comprehensive eye
      examination, including standardized refraction. Myopia, high myopia, and
      hyperopia were defined as a spherical equivalent (SE) in the right eye of more
      than -0.5 diopter (D), less than -5.0 D, and 0.5 D or more, respectively.
      Astigmatism was less than -0.5 D of cylinder. Anisometropia was defined as a
      difference in SE of >1.0 D between the 2 eyes. Only phakic eyes were analyzed.
      MAIN OUTCOME MEASURES: Myopia and other refractive errors. RESULTS: We included
      6491 (85.9% participation rate) eligible subjects in this study. Adjusted to the
      2000 China population census, the prevalence rate of myopia was 26.7% (95%
      confidence interval [CI], 25.6-27.8), hyperopia 15.9 % (95% CI, 15.0-16.8),
      astigmatism 24.5% (95% CI, 23.5-25.5), and anisometropia 7.7% (95% CI, 7.0-8.4).
      The prevalence of high myopia was 1.8% (95% CI, 1.5-2.1). Using a multivariate
      regression model, current smoking (odds ratio [OR], 0.7, 95% CI, 0.5-0.9), hours
      of reading (OR, 1.2; 95% CI, 1.1-1.4), diabetes (OR, 8.4; 95% CI, 2.2-32.5), and
      number of family members with myopia (OR, 1.3; 95% CI, 1.1-1.7, for each family
      member) were associated with myopia in younger persons (30-49 years). High school
      or higher education (OR, 1.8; 95% CI, 1.1-3.1), diabetes (OR, 1.6; 95% CI, 1.2
      2.7), nuclear opacity (OR, 1.7; 95% CI, 1.2-2.3), and number of family members
      with myopia (OR, 1.5; 95% CI, 1.2-1.9) were risk factors in persons >or=50 years
      of age. CONCLUSIONS: Myopia affects more than one quarter of rural Chinese
      persons >or=30 years of age. Myopia is more common in younger people and is
      associated with different risk factors than in older people.

PMID- 19744729
TI  - The ice pack test in the differential diagnosis of myasthenic diplopia.
AB  - PURPOSE: To investigate the diagnostic value and to establish threshold criteria
      for the ice pack test as an office preliminary test in the differential diagnosis
      of myasthenic diplopia in comparison with blepharoptosis. DESIGN: Prospective,
      comparative cohort study. PARTICIPANTS: Eighty-nine patients with a recent onset
      of diplopia, blepharoptosis, or both were evaluated with orbital cooling in a
      prospective manner. Forty-eight patients presented with diplopia, 25 patients
      with both blepharoptosis and ophthalmoplegia and 16 patients with blepharoptosis.
      TESTING: All patients had the ice pack applied for 5 minutes on both eyelids at
      the initial orthoptic evaluation. Increasing the duration of cooling to 10
      minutes was investigated in 36 diplopic patients. A complete diagnostic work-up
      was ordered and patients were followed up for a minimum of 6 months before
      diagnosis of myasthenia gravis was ascertained. MAIN OUTCOME MEASURES: Difference
      in cover test measurements in primary position or marginal reflex distance before
      and after the application of the ice pack, specific cause for diplopia and
      blepharoptosis. RESULTS: Fifteen patients were diagnosed as myasthenic. The
      optimal cutoff point for a positive response to the ice pack test proved to be a
      reduction in ocular deviation in primary position by 50% or by 10 prism diopters
      (PD) or more for presenting deviations larger than 20 PD. By this criterion,
      sensitivity for the detection of myasthenic diplopia was 76.9% (95% confidence
      interval [CI], 49.06%-92.50%) for the 5-minute application, compared with 92.3%
      (95% CI, 63.5%-98.9%) sensitivity demonstrated for blepharoptosis. Increasing the
      time of application to 10 minutes did not improve the diagnostic value of the
      test. Specificity was high (98.3%; 95% CI, 90.3%-99.9%) and was demonstrated even
      in patients with coexisting myasthenic and dysthyroid ophthalmopathy. Patients
      with oculomotor nerve paresis and Horner syndrome invariably were nonresponsive
      to the test. CONCLUSIONS: The ice pack test demonstrated high specificity and an
      acceptable sensitivity in the differential diagnosis of myasthenic diplopia. Data
      from this series suggest that a partial rather than a complete response to the
      ice pack test may be expected for myasthenic diplopia. Standardization of the
      method of application of the ice pack is critical for the interpretation of its
      effect.

PMID- 19744730
TI  - Lacrimal excretory system concretions: canalicular and lacrimal sac.
AB  - PURPOSE: To characterize the demographics of patients with dacryolithiasis and to
      compare patients who have canalicular concretions with patients who have lacrimal
      sac and duct dacryoliths. DESIGN: Comparative case series study and literature
      review. PARTICIPANTS: A total of 327 consecutive patients undergoing external
      dacryocystorhinostomy (DCR) between 1998 and 2008 at the University of Wisconsin
      Madison. Fifteen consecutive patients with the diagnosis of canaliculitis during
      this period were also included. METHODS: The charts of all patients were reviewed
      for age, sex, laterality, duration of symptoms, history of dacryocystitis,
      history of lacrimal system intervention, history of smoking, examination
      findings, result of canalicular probing and irrigation, and histopathologic
      evaluation of the dacryolith or canalicular concretion. If applicable, the
      canaliculus involved was noted, as was any history of purulent canalicular
      drainage or canalicular injury. MAIN OUTCOME MEASURES: Patient demographics,
      duration of symptoms, history of dacryocystitis, history of smoking, presence of
      fungi, or Actinomyces on histopathologic evaluation. Findings were compared with
      prior studies reported in the literature. RESULTS: Of the 327 patients undergoing
      DCR, 22 (6.7%) had dacryoliths; 11 of 15 patients (73.3%) with canaliculitis had
      canalicular concretions. Patients with canalicular concretions were older than
      those with dacryoliths at DCR: 70.6 years versus 51.1 years (P = 0.003). Women
      made up the majority of both groups: 9 of 11 patients (81.8%) with canalicular
      concretions and 13 of 22 patients (59.1%) with dacryoliths at DCR (P = 0.26). The
      mean duration of symptoms was 20.2 months among patients with canalicular
      concretions and 30.5 months in patients with dacryoliths at DCR (P = 0.66); 1 of
      11 patients (9.1%) with canalicular concretions smoked, compared with 9 of 21
      patients (42.9%) with dacryoliths at DCR (P = 0.11). Actinomyces was isolated
      from 10 of 11 canalicular concretions (90.9%) and only 3 of 22 dacryoliths
      (13.6%) from DCR (P<0.001). In none of the 11 canalicular concretions were fungi
      identified, compared with 2 of 22 dacryoliths (9.1%) from DCR (P = 0.54).
      CONCLUSIONS: The demographics of patients with dacryoliths and the histopathology
      of their concretions vary with the location of the dacryolith in the lacrimal
      excretory system.

PMID- 19744731
TI  - Variable expressivity and high penetrance of CYP1B1 mutations associated with
      primary congenital glaucoma.
AB  - OBJECTIVE: To investigate penetrance and expressivity of CYP1B1 genotypes
      associated with primary congenital glaucoma (PCG). DESIGN: Observational case
      series, systematic review, and comparative analysis of the literature.
      PARTICIPANTS: Forty probands affected with PCG, 16 siblings affected with PCG,
      and 103 siblings and 75 parents of the probands reported not to be affected by
      history. The participants were members of 40 unrelated families. METHODS:
      Mutations were screened by restriction fragment length polymorphism, allele
      specific polymerase chain reaction amplification, and direct sequencing.
      Ophthalmologic examination included slit-lamp biomicroscopy, intraocular pressure
      (IOP) measurement, gonioscopy, and high magnification stereoscopic fundus
      examination, followed by standard achromatic perimetry. MAIN OUTCOME MEASURES:
      Identification of subjects carrying CYP1B1 mutations. Glaucoma diagnosis based on
      slit-lamp examination, IOP measurement, gonioscopic findings, optic nerve
      appearance, and perimetry. RESULTS: Fifteen different homozygous or compound
      heterozygous mutant CYP1B1 genotypes were identified. Most probands and
      previously diagnosed subjects harbored G61E, R368H, R390H, and R469W mutations.
      Among the 178 apparently unaffected family members, 20 subjects from 12 families
      were observed to harbor 2 CYP1B1 mutations, suggesting an average penetrance of
      73% for all the mutations. These 20 subjects ranged in age from 14 to 54 years.
      R390H appeared to have a notably high penetrance. Penetrance was 50% in the
      subset of families with incomplete penetrance. Ophthalmologic examination on 14
      of the 20 apparently nonpenetrant individuals showed that 8 subjects were
      affected with juvenile open-angle glaucoma (JOAG) or primary open-angle glaucoma
      (POAG), and that 3 subjects were glaucoma suspect. One of the individuals with a
      JOAG diagnosis was the identical twin sibling of a proband affected with PCG.
      CONCLUSIONS: At least 57% of the PCG nonpenetrant individuals examined clinically
      were affected with JOAG or POAG to varying degrees, and overall penetrance of
      "affected CYP1B1 genotypes" with respect to glaucoma may be more than 90%. These
      findings suggest that "affected CYP1B1 genotypes" exhibit variable expressivity
      rather than nonpenetrance. The clinical implication of this observation is that
      seemingly unaffected relatives of patients with PCG, particularly those known to
      harbor CYP1B1 mutations, should undergo regular ophthalmologic examination to
      allow early diagnosis.

PMID- 19744732
TI  - Malignant transformation of congenital hypertrophy of the retinal pigment
      epithelium.
AB  - PURPOSE: To report a clinicopathologic correlation of an adenocarcinoma that
      arose from solitary congenital hypertrophy of the retinal pigment epithelium
      (CHRPE). DESIGN: Case report with clinicopathologic correlation. METHODS: A 56
      year-old black woman was referred for an asymptomatic fundus lesion in her left
      eye. It had features typical of CHRPE, but there was a small elevated nodule
      within the flat component, and the diagnosis was adenoma of the retinal pigment
      epithelium (RPE) arising from CHRPE. The lesion was observed periodically. The
      nodule slowly enlarged, and increasing amounts of lipoproteinaceous exudation
      accumulated in the adjacent retina. Thirteen years after the initial diagnosis,
      the patient returned with severe visual loss and no view of the fundus resulting
      from cataract and posterior synechia. Ultrasonography revealed a total retinal
      detachment and a pedunculated tumor measuring 7.5 mm in thickness. The eye was
      enucleated and studied histopathologically. MAIN OUTCOME MEASURES: Clinical
      evaluation and correlation of clinical findings with histopathologic results of
      the enucleated eye. RESULTS: Histopathologically, the mass was composed of a
      proliferation of atypical RPE cells with a marked infiltration of benign plasma
      cells. Typical features of CHRPE were present at the base of the tumor. The final
      diagnosis was adenocarcinoma arising from CHRPE. CONCLUSIONS: Congenital
      hypertrophy of the retinal pigment epithelium, once considered to be a benign and
      stationary lesion, may spawn a malignant neoplasm.

PMID- 19744733
TI  - Endothelial involvement in herpes simplex virus keratitis: an in vivo confocal
      microscopy study.
AB  - PURPOSE: To describe the appearance, frequency, and clinical consequences of
      corneal endothelial involvement in human herpes simplex virus (HSV) keratitis as
      seen by in vivo confocal microscopy (IVCM). DESIGN: Prospective observational
      case series. PARTICIPANTS: A total of 285 patients with HSV keratitis who visited
      the cornea department of the Rotterdam Eye Hospital between May 2005 and May
      2008. The control groups comprised the unaffected fellow eyes of patients with
      HSV keratitis, the eyes of 58 healthy volunteers, and the affected eyes of 62
      patients with inflammatory corneal disorders other than HSV. METHODS: We examined
      the eyes of all participants by IVCM and slit-lamp examination. For IVCM, corneas
      were scanned with Confoscan 3 or 4 (Nidek Technologies, Albignasego, Padova,
      Italy). MAIN OUTCOME MEASURES: All IVCM examinations were qualitatively reviewed
      for signs of endothelial deviations characteristic of endotheliitis. Endothelial
      cell density (ECD) was evaluated on the first and last visits of patients who
      were followed for more than 100 days. The differences in ECDs were calculated and
      converted to percent ECD change per year. RESULTS: Endothelial alterations
      characteristic of endotheliitis were detected by IVCM in 107 of 250 patients with
      HSV keratitis (43%). These deviations consisted of pseudoguttata, enlarged
      intercellular gaps, infiltration of inflammatory cells into the endothelial
      layer, loss of defined cell boundaries, spot-like holes, and endothelial
      denudation. All of these signs disappeared with appropriate antiviral and anti
      inflammatory treatment. However, the endothelium in eyes with endotheliitis
      characteristic alterations showed a significant decrease in ECD (10.3% per year)
      compared with healthy fellow eyes. CONCLUSIONS: IVCM allows earlier detection of
      endothelial alterations in patients with HSV keratitis compared with slit-lamp
      examination. Although endotheliitis-specific alterations appear to resolve, the
      corneal endothelium can become irreversibly damaged.

PMID- 19744734
TI  - Nine-year incidence and risk factors for age-related macular degeneration in a
      defined Japanese population the Hisayama study.
AB  - PURPOSE: To estimate the 9-year incidence and risk factors for age-related
      macular degeneration (AMD) in a general Japanese population. DESIGN: Population
      based, cohort study. PARTICIPANTS: In 1998, a total of 1775 Hisayama residents
      aged >or=40 years underwent a baseline eye examination. Of those, 1401 subjects
      (78.9%) took part in the follow-up eye examination in 2007 and were enrolled in
      the present study. METHODS: At both time points, the characteristics of AMD were
      determined by grading color fundus photographs using the Wisconsin Age-Related
      Maculopathy Grading System. MAIN OUTCOME MEASURES: Incident early and late AMD.
      RESULTS: The age-standardized, 9-year cumulative incidence of early AMD was
      10.0%, and that of late AMD was 1.4%. Men were found to have a significantly
      higher incidence of late AMD than women (age-adjusted odds ratio [OR], 2.97; 95%
      confidence interval [CI], 1.25-7.09). The incidence of both early and late AMD
      increased significantly with age. Multiple logistic regression analysis showed
      that older age (per 1 year; OR, 1.10; 95% CI, 1.05-1.16), smoking habits (OR,
      3.98; 95% CI, 1.07-14.7), and higher circulating white blood cell (WBC) count
      (per 1000 cells/mm(3)) (OR, 1.38; 95% CI, 1.07-1.79) were significantly
      associated with the development of late AMD. CONCLUSIONS: Our findings suggest
      that the 9-year incidences of late AMD are lower among the Japanese than among
      white people in Western countries, and it is higher than among black people.
      Smoking habits and higher circulating WBC count are significant risk factors for
      the development of late AMD in the Japanese.

PMID- 19744735
TI  - Demonstration of aluminum in amyloid fibers in the cores of senile plaques in the
      brains of patients with Alzheimer's disease.
AB  - Aluminum (Al) exposure has been reported to be a risk factor for Alzheimer's
      disease (senile dementia of Alzheimer type), although the role of Al in the
      etiology of Alzheimer's disease remains controversial. We examined the presence
      of Al in the Alzheimer's brain using energy-dispersive X-ray spectroscopy
      combined with transmission electron microscopy (TEM-EDX). TEM-EDX analysis allows
      simultaneous imaging of subcellular structures with high spatial resolution and
      analysis of small quantities of elements contained in the same subcellular
      structures. We identified senile plaques by observation using TEM and detected Al
      in amyloid fibers in the cores of senile plaques located in the hippocampus and
      the temporal lobe by EDX. Phosphorus and calcium were also present in the amyloid
      fibers. No Al could be detected in the extracellular space in senile plaques or
      in the cytoplasm of nerve cells. In this study, we demonstrated colocalization of
      Al and beta-amyloid (Abeta) peptides in amyloid fibers in the cores of senile
      plaques. The results support the following possibilities in the brains of
      patients with Alzheimer's disease: Al could be involved in the aggregation of
      Abeta peptides to form toxic fibrils; Al might induce Abeta peptides into the
      beta-sheet structure; and Al might facilitate iron-mediated oxidative reactions,
      which cause severe damage to brain tissues.

PMID- 19744736
TI  - Dinuclear organoiridium(III) mono- and bis-intercalators with rigid bridging
      ligands: synthesis, cytotoxicity and DNA binding.
AB  - The DNA binding and in vitro cytotoxicity of the dinuclear Ir(III) polypyridyl
      complexes [{(eta(5)-C(5)Me(5))Ir(dppz)}(2)(mu-pyz)](CF(3)SO(3))(4)1 and [{(eta(5)
      C(5)Me(5))Ir(pp)}(2)(mu-4,4'-bpy)](CF(3)SO(3))(4)2-4 (pp=dipyrido[3,2-d:2',3'
      f]quinoxaline (dpq), dipyrido[2,3-a:2',3'-c]phenazine (dppz),
      benzo[i]dipyrido[3,2-a:2',3'-c]phenazine (dppn)) with the rigid bridging ligands
      pyrazine (pyz) or 4,4'-bipyridine (4,4'-bpy) have been studied. Stable
      intercalative binding into CT DNA (calf thymus DNA) is indicated for the dppz
      complexes 1 and 3 by induced negative CD bands at about 300nm and large viscosity
      increases, with the individual measurements being in accordance with intrastrand
      bis-intercalation for 3 and mono-intercalation for 1. The observed interruption
      of specific interresidue NOE cross peaks from the relevant nucleobase H6/H8
      protons to the sugar H2'/H2'' protons of the preceding nucleotide is in
      accordance with bis-intercalation of complex 3 between the C3G18 and G4C17 base
      pairs and the T5A16 and A6T15 base pairs of the decanucleotide d(5'-CGCGTAGGCC
      3'). Complexes 1 and 3 exhibit a greatly improved uptake by HT-29 (colon
      carcinoma) cells and significantly improved in vitro IC(50) values of 1.8+/-0.1
      and 3.8+/-0.1microM towards this cell line in comparison to the mononuclear
      complex [(eta(5)-C(5)Me(5))IrCl(dppz)](CF(3)SO(3)) (IC(50)=7.4+/-0.9microM).

PMID- 19744737
TI  - Reverse resistance to radiation in KYSE-150R esophageal carcinoma cell after
      epidermal growth factor receptor signal pathway inhibition by cetuximab.
AB  - BACKGROUND AND PURPOSE: The purpose of our study is to examine the capacity of
      cetuximab to reverse radiation resistance and investigate molecular mechanisms in
      human radiation-resistant esophageal carcinoma cell line KYSE-150R. MATERIALS AND
      METHODS: The radioresistant cell line KYSE-150R was established by using
      fractionated irradiation (FIR). The KYSE-150R cell line was exposed to radiation,
      treatment with cetuximab, and combined treatment. Cell cycle distribution and
      apoptosis were analyzed using flow cytometry. Radiation survival was analyzed
      using clonogenic assays. RT(2) profiler PCR array was performed to analyze
      EGF/PDGF signaling pathway genes. RESULTS: The established esophageal carcinoma
      cell line KYSE-150R showed higher radioresistance than parental cell line.
      Cetuximab could reverse the radiation resistance of KYSE-150R cells. Cell cycle
      analysis showed that combination with radiation and cetuximab resulted in the
      accumulation of cells in G1 and G2/M phases, with the reduction of cells within
      the S phase. Cetuximab enhanced the apoptosis induced by radiation. RT(2)
      profiler array showed that some intracellular signaling genes deriving from
      EGF/PDGF signaling pathway regulated by cetuximab. CONCLUSIONS: Irradiation
      combined with EGFR blocked by cetuximab may reverse the resistance to radiation
      in radioresistant esophageal carcinoma cell. The mechanisms may include cell
      cycle perturbation and enhancement of radiation-induced apoptosis. Further
      studies are needed to evaluate the role of cetuximab in combination with
      radiotherapy in the management of esophageal carcinoma.

PMID- 19744738
TI  - Use of propyl paraben to control growth and ochratoxin A production by
      Aspergillus section Nigri species on peanut meal extract agar.
AB  - This study was carried out to determine the efficacy of the phenolic antioxidant
      propyl paraben (PP) under different interacting water activity (a(W)) and
      temperature regimes on lag phase, growth rate and Ochratoxin A production by
      Aspergillus section Nigri strains. In this experiment six Aspergillus section
      Nigri strains were used. Peanut meal extract agar (PMEA) was prepared at 2%. The
      a(W) of the medium was adjusted to 0.995, 0.980 and 0.930, PP levels of 1, 5, 10
      and 20 mmol/L were added to the basic medium. Plates were inoculated and
      incubated for 30 days at 18 and 25 degrees C. Lag phase (h) and radial growth
      rates (mm/day) were calculated. In control treatments, the lag phase increased
      and the growth rate decreased as a(W) reduced in all assayed strains. At all a(W)
      levels, when antioxidant concentrations increased the growth rate decreased. At
      5, 10 and 20 mmol/L of PP the strains were not able to reach the exponential
      phase and completely inhibited fungal growth and OTA production regardless of
      a(W) used in all the evaluated strains.

PMID- 19744739
TI  - Dual onset of type 1 diabetes mellitus and Graves' disease during treatment with
      pegylated interferon alpha-2b and ribavirin for chronic hepatitis C.
AB  - Currently, a combination therapy of pegylated (PEG) interferon (IFN) alpha-2b and
      ribavirin are being widely used for the treatment of chronic hepatitis C (CHC).
      We describe here a case of dual onset of type 1 DM accompanied by ketoacidosis,
      and Graves' disease during the combination therapy via the autoimmune process.

PMID- 19744740
TI  - CCR5Delta32 genotype is associated with outcome in type 2 diabetes mellitus.
AB  - AIMS: To test whether the genetic variant CCR5Delta32 in the CC-chemokine
      receptor 5, which is known to lead to CCR5 deficiency, is associated with
      mortality in type 2 diabetes patients. METHODS: We examined the effect of
      presence or absence of the CCR5Delta32 on overall and cardiovascular mortality
      risk in the Zwolle Outpatient Diabetes project Integrating Available Care
      (ZODIAC) cohort, a type 2 diabetes patient cohort. RESULTS: We studied 756
      patients with a mean duration of follow-up of 5.4 (+/- 1.4) years. 194 patients
      died during follow up of which 83 were cardiovascular deaths. 144 subjects (19%)
      carried the CCR5Delta32 deletion. CCR5Delta32 carriers had an adjusted hazard
      ratio of 0.62 (95%CI: 0.40-0.96; p=0.03) for all-cause mortality and 0.63 (95%CI:
      0.33-1.19; p=0.16) for cardiovascular mortality. CONCLUSIONS: The presence of
      CCR5Delta32 is associated with better survival in type 2 diabetes patients. These
      data suggest that it is worthwhile to explore the protective potential of
      pharmacological blockade of CCR5 in type 2 diabetic patients.

PMID- 19744741
TI  - Waist circumference and impaired fasting glucose screening in a Mediterranean
      population.
AB  - We evaluate the merits of routine waist circumference measurements for screening
      of impaired fasting glucose (IFG). Waist circumference and body mass index showed
      a strong association with the risk of IFG. The present data indicate the need for
      routine anthropometric measurements in clinical practice screening for IFG.

PMID- 19744742
TI  - First approaches to the monetary impact of environmental health disturbances in
      Germany.
AB  - OBJECTIVES: This article aims to describe essential conditions and starting
      points for the monetary evaluation of environmentally attributable diseases.
      Furthermore, a cost calculation within a scenario analysis is conducted for
      Germany. METHODS: To calculate the costs of environmental health effects we chose
      a disease-specific perspective. The national statistics of the Federal
      Statistical Office and the World Health Report burden of disease estimates were
      used to identify the most important disease categories for Germany. Based on an
      extensive literature research in computerized databases and the publications of
      national and international institutions, available costs of illness studies for
      Germany as well as environmental attributable fractions (EAFs) were identified.
      Based on these data environmental health costs were calculated with a top-down
      approach. RESULTS: Direct and indirect environmental costs of illness add up to
      15-62 billion euro(2006) per year depending on the specific scenario. From our
      results a tentative scheme is deduced of how the monetary environmental burden of
      specific diseases is composed and how it can be assigned to major environmental
      exposures and economic sectors which can be used in setting intervention
      priorities and evaluating intervention efficiency. CONCLUSION: Within this
      article, we were able to calculate environmental health costs for Germany based
      on available, easy to access data and deduce implications for environmental
      policy decision-making. However, there are restrictions in data quality, as the
      aetiology of some diseases with respect to environmental impacts is not very well
      documented and data has not been collected particularly for Germany.

PMID- 19744743
TI  - Plasma DNA levels in spiral CT-detected and clinically detected lung cancer
      patients: a validation analysis.

PMID- 19744744
TI  - Inhibition of mesothelin-CA-125 interaction in patients with mesothelioma by the
      anti-mesothelin monoclonal antibody MORAb-009: Implications for cancer therapy.
AB  - BACKGROUND: Mesothelin, a tumor differentiation antigen highly expressed in
      mesothelioma and ovarian cancer, is the receptor for CA-125 (MUC 16) and this
      interaction may play a role in tumor metastasis. MORAb-009 is a chimeric anti
      mesothelin monoclonal antibody. METHODS: Twenty-four patients with mesothelin
      expressing cancers were treated on a phase I study of MORAb-009 administered as
      an intravenous infusion (12.5-400mg/m(2)) weeklyx4 doses with 2 weeks off before
      the next cycle. This report summarizes the effect of MORAb-009 on serum CA-125
      kinetics in the eight patients with mesothelioma who had CA-125 levels measured
      before and at different time-points following therapy. RESULTS: MORAb-009
      treatment led to a marked increase in serum CA-125 levels in all patients
      including those without elevated CA-125 levels before therapy. The increase in CA
      125 levels was not due to disease progression since CA-125 levels decreased
      rapidly after stopping MORAb-009 therapy. No patients had signs of peritoneal or
      pleural inflammation as the possible cause of CA-125 rise. In addition, the
      elevated CA-125 levels were not due to MORAb-009 interfering with the laboratory
      assay used to measure CA-125. CONCLUSION: The increase in serum CA-125 produced
      by treatment with MORAb-009 is most likely due to MORAb-009 inhibiting the
      binding of tumor shed CA-125 to mesothelin present on mesothelial cells lining
      the pleural and peritoneal cavities. Inhibiting the mesothelin-CA-125 interaction
      could be a useful strategy to prevent tumor metastasis in mesotheliomas and
      ovarian cancer.

PMID- 19744745
TI  - Biomass partitioning, morphology and water status of four alfalfa genotypes
      submitted to progressive drought and subsequent recovery.
AB  - The predicted worldwide increase of arid areas and water stress episodes will
      strongly affect crop production. Numerous plants have developed specific
      morphological and physiological mechanisms as a means to increase their tolerance
      to drought. Water stress modifies dry matter partitioning and morphological
      components such as leaf area ratio (LAR), specific leaf area (SLA) and leaf
      weight ratio (LWR). Alfalfa has a wide-ranging distribution and is thus expected
      to show differing levels of drought tolerance. The aim of our study was to
      determine the effect of progressive drought and subsequent recovery in four
      alfalfa genotypes differing in drought sensitivity: three cultivars adapted to a
      Mediterranean climate, Tafilalet (TA), Tierra de Campos (TC) and Moapa (MO), and
      another representative of an oceanic climate, Europe (EU). Mild drought did not
      affect biomass production or water status in the studied varieties. Under
      moderate drought conditions, TA and MO showed decreased leaf production, which
      may help them to maintain relative water content (RWC). Despite observations that
      water stress did not affect root growth, after the recovery period, TA increased
      its root biomass, making higher water soil prospecting possible. Mediterranean
      cultivars modified LAR and SLA depending on water availability, whereas EU alters
      LWR. At the end of the experiment, TC was the most productive cultivar, but
      severe drought did not predict differences among cultivars. Severe water stress
      increased the root/shoot ratio in order to diminish water consumption and
      increase absorption of water. In spite of all cultivars showing a decreased LWR,
      TA also decreased SLA, which may suggest higher drought resistance. Morphological
      traits from Mediterranean cultivars, including the ability to alter SLA or LAR
      may be used for drought-tolerant cultivar improvement.

PMID- 19744746
TI  - Safety and tolerability of onabotulinumtoxinA in the treatment of facial lines: a
      meta-analysis of individual patient data from global clinical registration
      studies in 1678 participants.
AB  - BACKGROUND: OnabotulinumtoxinA for the treatment of facial lines is a widely used
      cosmetic medical procedure and, as such, the safety and tolerability profile is
      of interest to health care providers and patients. Based on data from individual
      studies that were conducted according to regulatory guidelines to provide
      adequate safety and efficacy data to support product licensure (registration
      studies), the overall benefit:risk profile of onabotulinumtoxinA for facial lines
      has been favorable. OBJECTIVE: Our objective was to increase statistical power
      through meta-analysis to detect treatment group differences in adverse event (AE)
      incidence that may not have been evident in individual registration studies.
      METHODS: Individual participant data (n = 1678) were from 6 randomized, double
      blind, placebo-controlled and 3 open-label studies. Two double-blind, placebo
      controlled studies were for lateral canthal lines (3-18 U/side) and all others
      were for glabellar lines (10 or 20 U). Doses used reflect global product labeling
      in countries where licensed. RESULTS: Participant population was non-Hispanic
      white (43%) or Asian (52%) and predominantly female (88%). In double-blind,
      placebo-controlled studies, overall AE incidence did not significantly differ by
      treatment group (onabotulinumtoxinA vs placebo). The only individual AEs with
      significantly greater incidence in the onabotulinumtoxinA group were eyelid
      sensory disorder (2.5% vs 0.3%, P = .004; verbatim phrases "tight," "pressured,"
      "heavy," "drooping feeling," "feeling of droopiness") and eyelid ptosis (1.8% vs
      0%, P = .02), both present only in glabellar studies. Overall treatment-related
      (per investigator) AE incidence was greater in the onabotulinumtoxinA group
      versus placebo (24% vs 16%, P = .005), and treatment-related eyelid edema was an
      additional AE with significantly higher incidence in the onabotulinumtoxinA group
      versus placebo (P = .04). Incidence of all 3 of these AEs significantly decreased
      as number of treatment cycles increased. Eyelid sensory disorder and eyelid edema
      were more common in Asian participants. Acne, injection site pruritus, oral
      herpes, rash, lower respiratory tract infection, dental caries, and eye pain were
      significantly more common in placebo-treated compared with onabotulinumtoxinA
      treated participants. Serious AE incidence did not significantly differ by
      treatment (onabotulinumtoxinA vs placebo) and no serious AEs were treatment
      related. There were no symptoms of weakness remote to the injection site or
      related to the central nervous system. LIMITATIONS: Limitations included: (1)
      highly visible efficacy of onabotulinumtoxinA may have resulted in reporting
      bias; (2) reliance on participant intervisit recall; (3) a relatively short
      follow-up period (1 year); (4) conclusions are based solely on the doses analyzed
      (ie, those used in the respective trials); and (5) exclusion of patients with
      severe medical disease in registration studies. CONCLUSION: This meta-analysis
      confirms the safety and tolerability of onabotulinumtoxinA for glabellar and
      lateral canthal lines, at the doses studied, based on the most comprehensive
      controlled safety analysis of onabotulinumtoxinA performed to date. The AEs
      observed were generally mild to moderate; most treatment-related AEs were related
      either to physical injection of product or local pharmacologic effects. Even with
      the increased statistical power of a large sample size, no new onabotulinumtoxinA
      associated AEs emerged.

PMID- 19744747
TI  - Aggressive subcutaneous panniculitis-like T-cell lymphoma with hemophagocytosis
      in two children (subcutaneous panniculitis-like T-cell lymphoma).
AB  - Subcutaneous panniculitis-like T-cell lymphoma is an uncommon form of cutaneous
      lymphoma in the pediatric population. It is characterized histologically by
      subcutaneous infiltration of pleomorphic cytotoxic T cells, mimicking a lobular
      panniculitis. Although usually described as having an indolent clinical course,
      the condition may be complicated by systemic involvement and hemophagocytic
      syndrome, resulting in a poorer prognosis. We present two pediatric patients with
      aggressive forms of subcutaneous panniculitis-like T-cell lymphoma complicated by
      hemophagocytic syndrome, and discuss the current literature.

PMID- 19744748
TI  - [Onset of celiac disease after acute hepatitis B infection].
AB  - Celiac disease is characterized by small intestinal mucosal injury and nutrient
      malabsorption in genetically susceptible individuals following dietary ingestion
      of gluten. The pathogenesis of the disease involves interactions between
      environmental, genetic, and immunologic factors. Transient infections or
      increased permeability of the mucosa may facilitate disease onset induced by the
      uptake of gluten peptides into a microenvironmental milieu in the small
      intestinal mucosa. We present two patients with onset of celiac disease after
      resolution of acute hepatitis B virus infection. The physiopathology of celiac
      disease is discussed and possible explanations for this association are proposed.

PMID- 19744749
TI  - [Coffee and mental health].

PMID- 19744750
TI  - Plasma citrulline is a marker of absorptive small bowel length in patients with
      transient enterostomy and acute intestinal failure.
AB  - BACKGROUND & AIMS: Small bowel disruption is often complicated by acute
      intestinal failure and can be corrected by chyme reinfusion (CR). Plasma
      citrulline ([Cit]) is a biomarker of the enterocyte mass. Our aim was to
      determine whether [Cit] could be a marker of absorptive intestinal mass or
      function by assessing whether CR could affect intestinal absorptive function and
      [Cit]. METHODS: Twenty-six patients with small bowel disruption and double
      enterostomy were treated with CR. Fecal wet weight, nitrogen and fat absorption,
      parenteral nutrition delivery and [Cit] were measured before and after the
      initiation of CR with a median follow-up of 30 days. RESULTS: CR decreased the
      intestinal wet weight output (median+/-IQ, 2384+/-969 vs. 216+/-242mLd(-1),
      P<0.0001) and parenteral nutrition dependence (65% vs. 8%, P<0.01). CR was
      associated with a rise in net nitrogen and fat digestive absorption and [Cit]
      (17.0+/-10.0 vs. 31.0+/-12.0micromolL(-1), P=0.0001). Before the initiation of
      CR, [Cit] correlated positively with the absorptive post-duodenal small bowel
      length (r=0.39, P=0.04), but not with the total post-duodenal small bowel length
      (r=0.11, P=0.60). CONCLUSION: CR allows for a dramatic improvement of intestinal
      absorptive function and a near doubling in [Cit] level. [Cit] is not a marker of
      overall intestinal mass, but of the absorptive small bowel function.

PMID- 19744751
TI  - Adductor pollicis muscle: reference values of its thickness in a healthy
      population.
AB  - BACKGROUND & AIMS: Adductor pollicis muscle is the only muscle which could be
      directly assessed, and its thickness could be useful in muscle mass assessment.
      Our objective is to determine values of adductor pollicis muscle thickness (APMT)
      in healthy subjects. METHODS: APMT was obtained using a skinfold caliper in 300
      healthy subjects, grouped by age and gender, in dominant (DAPMT) and non-dominant
      (NDAPMT) sides. All patients were assessed by Subjective Global Assessment (SGA).
      General characteristics of the subjects were obtained by a questionnaire.
      RESULTS: One hundred and fifty men and one hundred and fifty women were
      evaluated. Their mean age was 44.9+/-18.5 years and they were all well nourished.
      DAPMT mean values found in men were 26.1+/-4.4mm and in women, 19.8+/-3.3mm,
      respectively. NDAPMT mean values found in men and women were 25.1+/-4.4mm and
      18.7+/-3.1, respectively. Reference values for each gender and age group were
      created and values below the 5th percentile were considered as limit of
      normality. CONCLUSIONS: This study presents APMT reference values from a healthy
      population. New studies may demonstrate its role in the evaluation of muscle mass
      and its association with nutritional status.

PMID- 19744752
TI  - Engineered cartilage with internal porous high-density polyethylene support from
      bone marrow stromal cells: A preliminary study in nude mice.
AB  - Tissue-engineered cartilage may have potential for the construction of clinical
      implants for the treatment of congenital deformities or post-traumatic defects.
      However, the lack of seed cells is a challenge, as is the maintenance of ideal
      shape and size. We have used bone marrow stromal cells (BMSCs) and a pre-shaped
      polyglycolic acid (PGA)-porous high-density polyethylene composite scaffold to
      solve these problems. High-density polyethylene was carved into cylindrical rods
      and encircled with PGA fibres to form scaffolds. Porcine BMSC were seeded into
      the scaffold and cultured in chondrogenic medium (high-glucose Dulbecco's
      modified Eagle's medium with 10% (v/v) fetal bovine serum, dexamethasone 40
      ng/ml, transforming growth factor-beta1 10 ng/ml, and insulin-like growth factor
      50 ng/ml) for 3 weeks in vitro before the cell-scaffold constructs were implanted
      subcutaneously into nude mice. After 8 weeks of implantation, all specimens in
      the experimental group had formed mature cartilage around the polyethylene, and
      the prefabricated shapes and sizes were well maintained. The neoformed cartilage
      also grew into the pores of the scaffold with a fine interface between them; this
      gave the whole regenerated composite tissue characteristics similar to those of
      native cartilage. These results show that it is feasible to construct cartilage
      using BMSC and PGA-high-density polypropylene scaffolds. This may remove some of
      the obstacles that have prevented the clinical use of cartilage engineering such
      as limited volume, deformation, and a limited number of seed cells.

PMID- 19744753
TI  - Changes in running kinematics and kinetics in response to a rockered shoe
      intervention.
AB  - BACKGROUND: A suggested link between ambulatory mechanics and injury development
      has resulted in significant interest the development of footwear to change
      locomotion patterns. The purpose of this study was to test the hypothesis that
      there will be significant changes in the kinematics and kinetics at the ankle and
      minimal changes at the knee and hip in the mechanics of running in a shoe with a
      sagittal plane curvature relative to a flat soled shoe. METHODS: During running 3
      D lower extremity kinematics and kinetics for 19 healthy volunteers were
      quantified using an optoelectronics system and a force plate. Data were collected
      for a flat sole conventional shoe (New Balance 658 (Control)) and a shoe with a
      rounded sole in the sagittal plane (Masai Barefoot Technologies (MBT)). Data were
      compared for the two shoe conditions using paired Student t-tests (alpha=0.05).
      FINDINGS: The ankle dorsi-flexion angles at heel-strike and mid-stance were
      greater, while the ankle plantar and dorsi-flexion moments and peak ankle joint
      power were significantly lower with the MBT relative to the control (P<0.05).
      Decreases in the first medial GRF peak and the peak anterior GRF peak were also
      found for running in the MBT shoe. INTERPRETATION: Despite a major difference in
      sole geometry, accommodations to the rockered sole were found only at the ankle.
      These results suggest changes in ankle kinematics and kinetics may be used to
      minimize the effect of changes in sole rocker on limb dynamics. Thus, changes in
      shoe rocker may offer potential therapeutic opportunities for running related
      conditions at the ankle without substantial risk to the knee or hip.

PMID- 19744754
TI  - In vitro measurement of interface micromotion and crack in cemented total hip
      arthroplasty systems with different surface roughness.
AB  - BACKGROUND: Cemented stems with various surface roughnesses are used in total hip
      arthroplasty. However, it is not clear how the surface roughness of the stem
      affects the longevity of the implant. In this study, we investigated the effect
      of the stem roughness on the micromotion at the bone-cement and cement-implant
      interface and investigated cracks in the cement layer through in vitro
      measurement. METHODS: Stems with the same shape and material but with different
      surface roughness (polished with Ra=0.05 microm and matte-finished with Ra=0.83
      microm) were tested to measure the interface micromotion using custom-made
      sensors. The stems were implanted in five paired cadaver femurs and cyclic
      loading was applied to the femoral head to measure the interface micromotion.
      After loading, we measured the crack length and calculated the crack length
      density at the cement layer. FINDINGS: The difference in the interface
      micromotion between the polished stem and the rough stem was not significant
      except at the distal region of the cement-bone interface. More cracks were found
      at the distal region of the polished stem than at the rough stem. The magnitude
      of the cement crack length density did not correlate with the interface
      micromotion. INTERPRETATION: The results showed that the difference in the
      roughness between the polished and matte finishes did not significantly affect
      the micromotion and crack of the interface. However, more cement wear particles
      were expected in the matte-finished stem.

PMID- 19744755
TI  - Pressure characteristics at the stump/socket interface in transtibial amputees
      using an adaptive prosthetic foot.
AB  - BACKGROUND: The technological advances that have been made in developing highly
      functional prostheses are promising for very active patients but we do not yet
      know whether they cause an increase in biomechanical load along with possibly
      negative consequences for pressure conditions in the socket. Therefore, this
      study monitored the socket pressure at specific locations of the stump when using
      a microprocessor-controlled adaptive prosthetic ankle under different walking
      conditions. METHODS: Twelve unilateral transtibial amputees between 43 and 59
      years of age were provided with the Proprio-Foot (Ossur) and underwent an
      instrumented 3D gait analysis in level, stair, and incline walking, including
      synchronous data capturing of socket pressure. Peak pressures and pressure time
      integrals (PTI) at three different locations were compared for five walking
      conditions with and without using the device's ankle adaptation mode. FINDINGS:
      Highest peak pressures of 2.4 k Pa/kg were found for incline ascent at the calf
      muscle as compared to 2.1 k Pa/kg in level walking with large inter-individual
      variance. In stair ascent a strong correlation was found between maximum knee
      moment and socket pressure. The most significant pressure changes relative to
      level walking were seen in ramp descent anteriorly towards the stump end, with
      PTI values being almost twice as high as those in level walking. Adapting the
      angle of the prosthesis on stairs and ramps modified the pressure data such that
      they were closer to those in level walking. INTERPRETATION: Pressure at the stump
      depends on the knee moments involved in each walking condition. Adapting the
      prosthetic ankle angle is a valuable means of modifying joint kinetics and
      thereby the pressure distribution at the stump. However, large inter-individual
      differences in local pressures underline the importance of individual socket
      fitting.

PMID- 19744756
TI  - Nitrogen mediates above-ground effects of ozone but not below-ground effects in a
      rhizomatous sedge.
AB  - Ozone and atmospheric nitrogen are co-occurring pollutants with adverse effects
      on natural grassland vegetation. Plants of the rhizomatous sedge Carex arenaria
      were exposed to four ozone regimes representing increasing background
      concentrations (background-peak): 10-30, 35-55, 60-80 and 85-105 ppb ozone at two
      nitrogen levels: 12 and 100 kg N ha(-1) yr(-1). Ozone increased the number and
      proportion of senesced leaves, but not overall leaf number. There was a clear
      nitrogen x ozone interaction with high nitrogen reducing proportional senescence
      in each treatment and increasing the ozone dose (AOT40) at which enhanced
      senescence occurred. Ozone reduced total biomass due to significant effects on
      root biomass. There were no interactive effects on shoot:root ratio. Rhizome
      tissue N content was increased by both nitrogen and ozone. Results suggest that
      nitrogen mediates above-ground impacts of ozone but not impacts on below-ground
      resource translocation. This may lead to complex interactive effects between the
      two pollutants on natural vegetation.

PMID- 19744757
TI  - Transcriptional signatures in leaves of adult European beech trees (Fagus
      sylvatica L.) in an experimentally enhanced free air ozone setting.
AB  - Tropospheric ozone causes severe oxidative stress in plants. To investigate the
      transcriptional responsiveness of adult trees to ozone, fully-expanded sun and
      shade leaves of mature beech trees were harvested at four time points over the
      entire vegetation period in 2005 and 2006. Microarray analyses were conducted on
      leaves from trees grown in the field under ambient and twice-ambient ozone
      concentrations at Kranzberger Forst (Bavaria). Beech trees changed their
      transcript levels in response to ozone. In the years 2005 and 2006 different
      transcription patterns were observed; this may have been a result of different
      weather conditions and ozone uptake. Furthermore, we obtained differences in mRNA
      expression patterns between shade and sun leaves. In the ozone-treated sun leaves
      of 2005, slightly up- and down-regulated transcript levels were detected,
      particularly in the spring and autumn, whereas shade leaves clearly exhibited
      reduced mRNA levels, particularly at the end of the vegetation period. In 2006,
      this pattern could not be confirmed, and in the autumn, four other transcripts
      were slightly up-regulated in ozone-treated shade leaves. In addition, two other
      transcripts were found to be influenced in sun leaves in the spring/summer. While
      we detected changes in the levels of only a few transcripts, the observed effects
      were not identical in both years. In conclusion, elevated ozone exhibited very
      small influence on the transcription levels of genes of mature beech trees.

PMID- 19744758
TI  - Posttraumatic stress disorder and quality of life: extension of findings to
      veterans of the wars in Iraq and Afghanistan.
AB  - The wars in Iraq and Afghanistan-Operation Iraqi Freedom and Operation Enduring
      Freedom, or OEF/OIF-have created unique conditions for promoting the development
      of psychological difficulties such as posttraumatic stress disorder (PTSD). PTSD
      is an important outcome because it can affect quality of life, impairing
      psychosocial and occupational functioning and overall well-being. The literature
      on PTSD and quality of life in OEF/OIF Veterans is at an early stage, but the
      consistency of the evidence is striking. Our review indicates that the findings
      on PTSD and quality of life in OEF/OIF veterans are comparable to findings
      obtained from other war cohorts and from nonveterans as well. Even though the
      duration of PTSD in OEF/OIF Veterans is much shorter than in Vietnam Veterans,
      for example, those with PTSD in both cohorts are likely to experience poorer
      functioning and lower objective living conditions and satisfaction. The review
      ends with discussion of the implications of the evidence for research and
      clinical practice.

PMID- 19744759
TI  - What is the association between obsessive-compulsive disorder and eating
      disorders?
AB  - Because eating disorders (EDs) and obsessive compulsive disorder (OCD) co-occur
      at high rates and can have functionally similar clinical presentations, it has
      been suggested that both constructs might be part of a common spectrum of
      disorders. Identifying the relationship between EDs and OCD may lead to the
      discovery of important shared core disease processes and/or mechanisms for
      maintenance. The objective of this paper is to understand the relationship
      between EDs and OCD by systematically reviewing epidemiological, longitudinal and
      family studies guided by five models of comorbidity posited by Klein and Riso
      (1993) and others. Though this literature is relatively small, the preponderance
      of evidence from these studies largely suggests that OCD/ED co-occur because of a
      shared etiological relationship. Limitations to extant literature, and
      suggestions for future research are discussed.

PMID- 19744760
TI  - Mild traumatic brain injury and posttraumatic stress disorder in returning
      veterans: perspectives from cognitive neuroscience.
AB  - A significant proportion of military personnel deployed in support of Operation
      Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) has been exposed to war
      zone events potentially associated with traumatic brain injury (TBI) and
      posttraumatic stress disorder (PTSD). There has been significant controversy
      regarding healthcare policy for those service members and military veterans who
      returned from OEF/OIF deployments with both mild TBI and PTSD. There is currently
      little empirical evidence available to address these controversies. This review
      uses a cognitive neuroscience framework to address the potential impact of mild
      TBI on the development, course, and clinical management of PTSD. The field would
      benefit from research efforts that take into consideration the potential
      differential impact of mild TBI with versus without persistent cognitive
      deficits, longitudinal work examining the trajectory of PTSD symptoms when index
      trauma events involve TBI, randomized clinical trials designed to examine the
      impact of mild TBI on response to existing PTSD treatment interventions, and
      development and examination of potential treatment augmentation strategies.

PMID- 19744761
TI  - Four-year clinical performance and marginal analysis of pressed glass ceramic
      inlays luted with ormocer restorative vs. conventional luting composite.
AB  - OBJECTIVES: The aim of the present study was to evaluate the ormocer Definite
      (Degudent, Hanau, Germany) as resin luting cement. METHODS: In a controlled
      prospective clinical study, 57 Cergogold (Degudent) all-ceramic inlays were
      placed in 24 patients by four dentists. The restorations were luted with two
      different systems (MD=Definite Multibond+Definite; SV=Syntac+Variolink Ultra,
      Ivoclar Vivadent, Liechtenstein) without lining. At baseline, after 12, 24, and
      48 months, restorations were examined according to modified USPHS scores and
      criteria. RESULTS: One patient including three restorations missed the 4 years
      recall (dropout). After 48 months of clinical service, four restorations in four
      patients (three luted with Definite, one with Variolink) failed due to inlay
      fracture (n=3) and tooth fracture (n=1), all other fillings were clinically
      acceptable (survival rate 93.3% for Definite vs. 95.2% for Variolink; Kaplan
      Meier algorithm). Except for the rate of hypersensitivity at baseline (MD: 27%;
      SV 0%; p<0.05), no differences were evident between the luting cements at any
      recalls (Mann-Whitney U-test; p>0.05). Between the four recalls, a statistically
      significant deterioration was detected for both groups regarding the criteria
      marginal adaptation, filling integrity (cracks/chippings/fractures), and tooth
      integrity (Friedman test; p<0.001). After 4 years, mainly distinct deterioration
      with marginal fractures or chippings in proximal and marginal areas of the inlays
      were observed. No differences were found for surface roughness, color matching,
      and proximal contact (p>0.05). CONCLUSIONS: For luting of ceramic inlays, only
      slight differences between the two luting systems were detectable.

PMID- 19744762
TI  - Abnormal vital signs are associated with an increased risk for critical events in
      US veteran inpatients.
AB  - AIM: Establish the frequency of abnormal vital signs in medical and surgical ward
      patients; study their association with "critical events," which for the purposes
      of this study, were mortality, cardiac arrests and unplanned ICU transfers.
      DESIGN AND METHODS: Four-month prospective, observational cohort study;
      University-affiliated US Veteran's hospital. Vital signs from all regular ward
      medical and surgical inpatients were recorded over the study period and compared
      with records of cardiac arrests, mortality and ICU admissions. RESULTS: Using the
      Hospital's Medical Emergency Team criteria to define normal/abnormal thresholds
      for vital signs, abnormal vital signs (VS(MET)) were found in 16% of patients; of
      these; 35% experienced a critical event vs. 2.5% in the patients with normal
      vital signs (OR 21, 95% CI 12-35, p<0.001). The sensitivity of VS(MET) to predict
      a critical event was 0.72 and the positive predictive value was 0.35; sensitivity
      decreased to 0.28 and positive predictive value increased to 0.78 for patients
      that had two different VS(MET). Survival was significantly lower in both medical
      and surgical patients with VS(MET) at both 30 days and at 1 year following
      discharge (p<0.02). Both medical and surgical patients with VS(MET) had twice the
      length of stay of patients with normal vitals (3 vs. 7 days; p<0.001).
      CONCLUSIONS: Even single recordings of VS(MET) signaled increased risk for
      critical events in hospital ward patients. Use of vital signs as criteria for
      additional patient assessment and possible ICU admission appears justified.
      Development of abnormal vitals during hospitalization may signify impaired
      physiologic reserve that places a patient at higher risk for mortality after
      discharge.

PMID- 19744763
TI  - Glucagon treatment for bradycardia and a junctional rhythm caused by excessive
      beta-blockade.

PMID- 19744764
TI  - Role of resuscitative emergency field thoracotomy in the Japanese helicopter
      emergency medical service system.
AB  - OBJECTIVE: We investigated whether emergency thoracotomy (ET) performed in pre
      hospital settings contributed to saving the lives of blunt trauma patients with
      impending or recent cardiac arrest. METHODS: Eighty-one consecutive cardiac
      arrest patients with blunt trauma were performed ET before or after arrival at
      the emergency department (ED). These were reviewed retrospectively and were
      classified into the following three groups: (1) an emergency field thoracotomy
      was performed (EFT group, n=34); (2) a doctor dispatched to the scene, but the
      thoracotomy was performed in the ED (EDT-a group, n=10); and (3) no doctor
      dispatched to the scene, and the thoracotomy was performed in the ED (EDT-b
      group, n=37). The patients in the EFT and EDT-a groups were managed within the
      Japanese helicopter emergency medical service system with a doctor dispatched to
      the scene. RESULT: The time between the arrival of the EMT at the scene and the
      start of the thoracotomy was significantly shorter in the EFT group than in the
      EDT-b group (19.2+/-7.9 min vs. 30.7+/-6.8 min, p<0.001). In the EFT group, the
      "ICU admission" rate was significantly higher among the patients who experienced
      cardiac arrest after the EMT arrival than among the patients who experienced
      cardiac arrest before the EMT arrival (70% vs. 8%, p=0.001). Unfortunately,
      however, there were no survivors in this series. CONCLUSION: These findings
      indicate that "early access" to a doctor's expertise and the performance of an
      "emergency field thoracotomy" might be two important factors for improving the
      possibility of saving the lives of blunt trauma patients with impending or recent
      cardiac arrest.

PMID- 19744765
TI  - Evaluation of the tocolytic effect of morphine in a mouse model of
      lipopolysaccharide-induced preterm delivery: the role of nitric oxide.
AB  - OBJECTIVES: This study evaluated the preventive effect of morphine on
      lipopolysaccharide (LPS)-induced preterm delivery and the contribution of the
      nitric oxide pathway as a mechanism involved in this process. STUDY DESIGN:
      Pregnant mice were treated with LPS: (a) single doses of 35, 50 and 75 microg/kg;
      (b) double doses of 25, 35 and 50 microg/kg with a 3-h interval, on gestational
      day 15. Each treatment group consisted of 5-10 mice and the main outcome
      measurements were the incidence and gestational duration after injection of the
      last LPS dose. Administration of LPS (35 microg/kg, with a 3-h interval) induced
      the highest incidence of preterm delivery in mice. For investigation of morphine
      effects on preterm delivery, animals were treated either with a single dose (10
      or 20 mg/kg), or with double doses (5 or 10 mg/kg; with a 3-h interval) of
      morphine, 1h before each LPS injection. To assess the involved mechanism, either
      naltrexone (5 and 10 mg/kg) or N(omega)-nitro-l-arginine methyl ester (l-NAME, 2
      10 mg/kg) was administered 1h before the first morphine administration. Any
      interaction in the incidence and/or time of preterm delivery was ruled out by
      other groups which received naltrexone or l-NAME, each alone. Data were analyzed
      by the Fisher's exact test for determination of preterm delivery incidences and
      by the one-way analysis of variance, followed by post-test Tukey, for
      determination of gestational duration. RESULTS: Although LPS induced premature
      labor and decreased the delivery time to gestational day 16, morphine treatment
      significantly decreased the incidence of LPS-induced premature labor by 50% and
      increased the delivery time to gestational day 17.6. Naltrexone (5 mg/kg) did not
      influence morphine-induced attenuation of preterm delivery rate and pregnancy
      duration. Unlike naltrexone, l-NAME (2 mg/kg) increased the rate of preterm
      delivery to 100% and decreased pregnancy duration to gestational day 16 in
      morphine-treated mice. In fact, l-NAME significantly attenuated morphine's
      preventive effect on preterm delivery. CONCLUSION: Morphine increases the
      gestational duration and decreases the preterm delivery rate induced by LPS
      probably through modulation in NO release. l-NAME, unlike naltrexone, reversed
      the effect of morphine on preterm delivery, demonstrating the involvement of
      nitric oxidergic pathway.

PMID- 19744766
TI  - Iminothiol/thiourea tautomeric equilibrium in thiourea lipids impacts DNA
      compaction by inducing a cationic nucleation for complex assembly.
AB  - Our research on lipidic vectors for transfection led us to develop thiourea
      lipids able to interact with DNA. Hence, we developed a series of
      lipopolythioureas based on the strong hydrogen bond donor ability of thiourea.
      More recently we have reported a branched hydroxylated bis-thiourea derivative
      with interesting transfecting properties. The last step of the syntheses involved
      a strong acidic condition, leading to an unstable product upon storage. Therefore
      we designed a new synthesis in mild acidic conditions. Though they exhibit the
      same mass, the lipids obtained in the two different conditions differ by their
      interaction with DNA. We therefore explored the physicochemical properties of
      these two lipids by different means that we describe in this article. In order to
      insure easier and reliable (13)C-NMR studies of the thiourea group we have
      designed the synthesis of the corresponding (13)C-labeled thiourea lipids. We
      have thus shown that when the lipid was submitted to mildly acidic medium; only
      the thiourea group was observed; while a thiourea/charged and/or uncharged
      iminothiol tautomeric equilibrium formed when the last step of the synthesis was
      submitted to low pH. NMR experiments showed that this tautomeric equilibrium
      could not form in polar solvents. However, UV experiments on the liposomal form
      of the lipopolythiourea showed the presence of the tautomers. Lipid/DNA
      interaction consequently differed according to the acidic treatment applied.
      Eventually, these results revealed that on this particular thiourea lipid,
      electrostatic interactions due to cationic thioureas are likely to be responsible
      for DNA compaction and that this tautomeric form of the thiourea could be
      stabilised by hydrogen bonds in a supramolecular assembly. Nevertheless, this
      does not reflect a general thiourea lipid/DNA interaction as other thiourea
      lipids that are able to compact DNA do not undergo an acidic treatment during the
      final stage of their synthesis.

PMID- 19744767
TI  - Potential for rainwater use in high-rise buildings in Australian cities.
AB  - Rainwater is a traditional but underutilized water resource that has today had a
      resurgence due to the worldwide water crisis. This paper demonstrates the
      outcomes of research on the feasibility of rainwater use in high-rise residential
      envelopes for four Australian cities of Melbourne, Sydney, Perth and Darwin.
      Different climate patterns and various levels of water demand management were
      established for determination of storage dimensions; annual tank water use;
      reduction in both imported water flow and stormwater disposal; and water spillage
      from tanks. High level water demand management was a profoundly effective tool
      for reducing potable water supply, especially in combination with rainwater use.
      The economic feasibility of rainwater use systems were estimated; with Sydney
      having the shortest payback period compared to other cities either both with 3A
      rated appliances (8.6 years) or 5A ones installed (10.4 years). That was due to
      the higher and more consistent rainfall in Sydney. An outcome of this study was
      that Sydney was likely most suited to rainwater use, followed by Perth, Darwin,
      and then Melbourne. The objective of this study was to fill in the gap in
      estimating feasibility of rainwater use in various Australian cities. This
      investigation endeavors to provide assistance to water authorities and urban
      planners of Australian cities with the consideration of the potential of
      rainwater harvesting.

PMID- 19744768
TI  - Long-term evaluation of coal fly ash and mine tailings co-placement: a site
      specific study.
AB  - This study presents the results of a laboratory investigation conducted to
      evaluate the efficiency of coal fly ash to control the formation of acid mine
      drainage (AMD) from mine waste. Site-specific materials, coal fly ash from
      Atikokan Thermal Generating Station and mine tailings from Musselwhite mine, were
      mixed at different proportions for the investigation of the drainage chemistry
      and the optimal mix using static testing (acid-base accounting) and kinetic
      (column) testing. The acid-base accounting (ABA) results indicated that the fly
      ash possessed strong alkaline (neutralization) potential (NP) and could be used
      in the management of reactive mine tailings, thus ensuring prevention of AMD in
      the long-term. Column tests conducted in the laboratory to further investigate
      long-term performance of fly ash in the neutralization and prevention of acid
      mine drainage from tailings similarly showed that mixing fly ash with mine
      tailings reduces dissolution of many heavy metals from tailings by providing
      alkalinity to the system. It was found that a fly ash to tailings mass ratio
      equal to or greater than 15% can effectively prevent AMD generation from
      Musselwhite mine tailings in the co-placement approach.

PMID- 19744770
TI  - Frontal lobe atrophy is associated with small vessel disease in ischemic stroke
      patients.
AB  - BACKGROUND: The pathogenesis of frontal lobe atrophy (FLA) in stroke patients is
      unclear. We aimed to ascertain whether subcortical ischemic changes were more
      associated with FLA than with parietal lobe atrophy (PLA) and temporal lobe
      atrophy (TLA). METHODS: Brain magnetic resonance images (MRIs) from 471 Chinese
      ischemic stroke patients were analyzed. Lobar atrophy was defined by a widely
      used visual rating scale. All patients were divided into non-severe, mild
      moderate, and severe atrophy of the frontal, parietal, and temporal lobe groups.
      The severity of white matter lesions (WMLs) was rated with the Fazekas' scale.
      Clinical and radiological features were compared among the groups. Subsequent
      logistic regressions were performed to determine the risk factors of atrophy and
      severe atrophy of the frontal, parietal and temporal lobes. RESULTS: The
      frequency of FLA in our cohort was 36.9% (174/471). Severe FLA occurred in 30
      (6.4%) patients. Age, previous stroke, and periventricular hyperintensities (PVH)
      (odds ratio (OR)=1.640, p=0.039) were independent risk factors of FLA. Age and
      deep white matter hyperintensities (DWMH) (OR=3.634, p=0.002) were independent
      risk factors of severe FLA. PVH and DWMH were not independent risk factors of PLA
      and TLA. CONCLUSION: Frontal lobe atrophy in ischemic stroke patients may be
      associated with small vessel disease. The association between WMLs and FLA was
      predominant over atrophy of the parietal and temporal lobes, which suggests that
      the frontal lobe may be vulnerable to subcortical ischemic changes.

PMID- 19744771
TI  - Puusepp's sign--clinical significance of a forgotten pyramidal sign.
AB  - The pyramidal signs in the lower extremity can be divided into three groups: (1)
      Babinski's group characterised by dorsoflexion of the great toe, (2) pyramidal
      signs marked by plantar flexion of the toes (e.g. Rossolimo's sign), and (3)
      synkinetic movements such as Strumpell's phenomenon. Puusepp's sign described by
      the Estonian neurologist and neurosurgeon Ludvig Puusepp belongs to none of these
      three groups. Its eliciting does not differ from that of Babinski's sign. The
      response, however, is different and consists of a tonic slow abduction of the
      little toe. We showed its relevance on the basis of clinical examination of six
      patients: four females aged 29, 50, 43 and 57 years and two males aged 42 and 49
      years. The diagnoses were as follows: a new relapse of multiple sclerosis, a
      secondary progressive multiple sclerosis, a left middle cerebral artery stroke, a
      lumbago resulting in L3-L4 fusion surgery, an amyotrophic lateral sclerosis and a
      left intracerebral haemorrhage respectively. Puusepp's sign was the only
      elicitable pyramidal sign in all the patients but two. The 50-year-old female
      patient revealed on neurological examination Babinski's sign on the left side and
      Puusepp's sign on the right side. The testing of pyramidal signs in the 57-year
      old woman displayed a bilateral Strumpell's sign and a left Puusepp's sign. These
      six cases showed that although rarely recognized in the clinical practice
      Puusepp's sign contributed to establishing the diagnosis of a central motor
      neuron involvement in the case of an absent Babinski's sign. Thus, its testing
      does not differ from that of Babinski's sign which requires only a little
      attention from the examiner, but provides an important piece of clinical
      information.

PMID- 19744772
TI  - Loss of function of PTEN alters the relationship between glucose concentration
      and cell proliferation, increases glycolysis, and sensitizes cells to 2
      deoxyglucose.
AB  - PTEN loss of function enhances proliferation, but effects on cellular energy
      metabolism are less well characterized. We used an inducible PTEN expression
      vector in a PTEN-null glioma cell line to examine this issue. While proliferation
      of PTEN-positive cells was insensitive to increases in glucose concentration
      beyond 2.5mM, PTEN-null cells significantly increased proliferation with
      increasing glucose concentration across the normal physiologic range to
      approximately 10mM, coinciding with a shift to glycolysis and "glucose
      addiction". This demonstrates that the impact of loss of function of PTEN is
      modified by glucose concentration, and may be relevant to epidemiologic results
      linking hyperglycemia to cancer risk and cancer mortality.

PMID- 19744773
TI  - Characterization of native microalgal strains for their chromium bioaccumulation
      potential: phytoplankton response in polluted habitats.
AB  - Due to its various uses, Cr contamination has become widespread in a diverse
      array of environments. The present study was carried out during 2007-2008 to
      investigate the accumulation potential of metals (Cr, Cu, Fe, Mn, Ni and Zn) and
      metalloid (As) by green (GA) and blue green (BGA) microalgae growing naturally in
      selected Cr-contaminated sites in districts Unnao and Kanpur (Uttar Pradesh,
      India). This investigation is a preliminary work to identify suitable native
      microalgae for biomonitoring and phytoremediation purposes. A total of 22 GA and
      11 BGA were encountered in three seasons (summer, rainy and winter). Among these,
      the accumulation potential was evaluated in high biomass producing strains of BGA
      (three) and GA (nine). The maximum accumulation of Cr was shown by Phormedium
      bohneri (8550 microg g(-1)dw) followed by Oscillatoria tenuis (7354 microg g(
      1)dw), Chlamydomonas angulosa (5325 microg g(-1)dw), Ulothrix tenuissima (4564
      microg g(-1)dw), and Oscillatoria nigra (1862 microg g(-1)dw); all of which
      demonstrated a transfer factor of >10% for Cr. The results also indicate that the
      phytoplankton diversity was modified by Cr pollution. BGA represented the
      dominant community where Cr concentration was higher (11.84 and 2.27 mg L(-1))
      (r=0.695), whereas GA showed negative correlation with respect to Cr
      concentration (r=-0.567). In conclusion, different algal species were able to
      grow in Cr-contaminated sites and to accumulate significant amounts of Cr with a
      high transfer factor.

PMID- 19744774
TI  - Development of a new SPME-HPLC-UV method for the analysis of nitro explosives on
      reverse phase amide column and application to analysis of aqueous samples.
AB  - A rapid, simple, sensitive and accurate quantitative method has been developed
      for the determination of eleven nitroaromatic components by solid phase
      microextraction (SPME) coupled to high performance liquid chromatography (HPLC)
      with UV detection from aqueous samples. PDMS/DVB resin fiber (60 microm) was used
      for concurrent extraction of all the analytes from aqueous matrix. Static
      desorption was carried out in the desorption chamber of SPME-HPLC interface
      containing mobile phase; methanol:water 43:57 (v/v) with subsequent liquid
      chromatographic analysis at isocratic flow rate of 1.3 mL/min and detection at
      254 nm. A reverse phase amide column (5 microm) was used as a separation medium.
      The limit of detection (S/N=3) for TNT and Tetryl was found to be 0.35 and 0.54
      ng/mL, respectively. Developed method has been applied successfully to the
      analysis of aqueous samples obtained from environmental and industrial sources
      like river water, ground water, drinking water and industrial waste water.

PMID- 19744775
TI  - New amphoteric flocculant containing beta-cyclodextrin, synthesis,
      characterization and decolorization properties.
AB  - To react with the cationic monomer, N-trimethylaminoethylmethacrylate chloride
      (TMAEMC), a beta-CD derivative carrying vinyl carboxylic acid groups (beta-CD
      MAH) was designed and synthesized via esterfying reaction between beta-CD and
      maleic anhydride (MAH). Whereafter, a water-soluble amphoteric flocculant, the
      copolymer of TMAEMC and beta-CD-MAH (beta-CD-MAH-TMAEMC) has been synthesized by
      means of free radical copolymerization using the ammonium persulfate (APS) and
      sodium bisulfite (SBS) redox system as the initiator. The copolymer structure was
      demonstrated by FT-IR, (1)H NMR, SEM characterizations. Its excellent flocculated
      decolorization properties were evaluated with Acid Light Yellow 2G solutions
      using a jar test method. With the mass ratio of 1/10 (w/w) between the flocculant
      and dye, and at pH 4 and 20 degrees C of the initial dye solution, the maximum
      color removal reached. The charge neutralization played a dominant role during
      the flocculated decolorization process, although the inclusion of dye molecules
      into the cavities of beta-CD well maintained in side chain of beta-CD-MAH-TMAEMC
      also contributed to the conglomerates and floccules.

PMID- 19744776
TI  - Effective removal of disinfection by-products and assimilable organic carbon: an
      advanced water treatment system.
AB  - The purpose of this work is to investigate an advanced water treatment system
      changes on disinfects by-products (DBPs) precursors removal efficiencies of
      treatment plant and associated trihalomethanes (THMs) and haloacetic acids
      (HAA(5)) formation and assimilable organic carbon (AOC) in reduction from raw
      water through finished water of Fong-shan Water Treatment Plant (FSWTP) in
      Kaohsiung City, Taiwan. Drinking water samples were collected from an advanced
      water treatment plant during March-October 2008. In the formation of DBPs,
      advanced water treatment processes efficiently removed THMs and HAA(5). The
      concentrations of THMs and HAA(5) in finished water were reduced to 13.97
      microg/L and 17.67 microg/L, respectively. In this investigation, the AOC was
      reduced effectively by ozonation and biological activated carbon (BAC) processes.
      Experimental results of this 6-month investigation indicate that AOC
      concentrations in the finished water can meet the WTP criterion of 50 microg
      acetate-C/L in the world. Results of this study provide a valuable reference for
      solving DBPs and AOC control of water treatment plants and the setting of
      regulations in Taiwan.

PMID- 19744777
TI  - Kinetics and thermodynamics of adsorption of cadusafos on soils.
AB  - Laboratory batch experiments were designed to study the adsorption of cadusafos
      on two types of soils: clay loamy and sandy, collected from two regions around
      the Nile Delta in Egypt. The adsorption process is fast reaching equilibrium in
      60 min, decreases with increasing soil mass and independent on pH in the range 3
      11. The experimental results were well fitted to linear partition model, and to a
      lesser extent to Freundlich non-linear model, Temkin and Dubinin-Radushkevich
      models. However, the 1/n parameter of Freundlich relation being of value around
      one supported the linear partition model. The K(d) values obtained from the
      linear model were 4.20 and 2.74 L/g for sandy and clay soils, respectively. The
      energy of adsorption calculated from D-R equation was 4.36 and 5.04 kJ/mol for
      clay and sandy soils, respectively, in the range assigned to physical forces.
      This kind of weak interaction, together with pH-independence implies that for the
      studied soils the organic content (that is higher in the clay soil) is not a
      major parameter in the adsorption of cadusafos. Water movement taking place more
      readily in sandy soil caused increased uptake relative to the case of clay soil.
      The higher uptake in sandy soil denotes that cadusafos may be mobile with a
      potential to leach and eventually pollutes ground water and surface water. The
      kinetics of adsorption was well fitted by the pseudo-second order equation. The
      intraparticles diffusion is of lower significance in case of sandy soil than in
      clay soil. Thermodynamic parameters indicated that the adsorption is spontaneous,
      endothermic accompanied by increase in entropy.

PMID- 19744778
TI  - CdS-sensitized TiO2 in phenazopyridine photo-degradation: catalyst efficiency,
      stability and feasibility assessment.
AB  - Mineralization of phenazopyridine, 1, in water, under solar-simulator radiation
      was efficiently achieved using nanoparticle CdS-sensitized rutile TiO(2),
      TiO(2)/CdS, 2, as photo-catalysts. Despite that, 2 showed two main drawbacks.
      Firstly, the system was difficult to recover by simple filtration, and demanded
      centrifugation. Secondly, the sensitizer CdS showed relatively high tendency to
      leach out hazardous Cd(2+) ions under photo-degradation reaction conditions. In
      an attempt to solve out such difficulties, 2 was supported onto sand surface. The
      sand/TiO(2)/CdS system, 3, was easier to recover but showed slightly lower
      catalytic activity compared to 2. On the other hand, the support failed to
      prevent leaching of Cd(2+). This indicates limited future applicability of CdS
      sensitized TiO(2) photo-catalyst systems, in solar-based water purification
      strategies, unless leaching out tendency is completely prevented.

PMID- 19744779
TI  - Production and characterization of pyrolytic oils by pyrolysis of waste machinery
      oil.
AB  - The main objective of this work is to propose an alternative method for
      evaluation of the waste machinery oil which is an environmental problem in
      Turkey. For this purpose, pyrolysis of waste machinery oil was conducted in a
      tubular reactor. Effect of the experimental conditions (various temperatures,
      catalyst type) on the formation of pyrolytic oil, gas, and char was investigated.
      Nickel supported on silica and zeolite (HZSM-5) were used as catalysts.
      Properties of the pyrolytic oils were characterized by gas chromatograph equipped
      with a mass selective detector (GC-MS), gas chromatography with flame ionization
      detector (GC-FID for boiling point range distribution), nuclear magnetic
      resonance ((1)H NMR) spectroscopy, higher heating value measurement, and
      elemental analysis. The behavior of the metals in the waste machinery oil and the
      pyrolytic oil samples was also quantitatively detected by inductively coupled
      plasma (ICP) analysis. As, Cd and Cr contents of the all pyrolytic oils were
      found as <0.05 ppm, while Cu content of the pyrolytic oils varied between 0.3 ppm
      and 0.61 ppm. Only Vanadium contents of the pyrolytic oils obtained at 800
      degrees C (0.342 ppm) and in the presence of HZSM5 (0.57 ppm) increased compared
      to that obtained by waste machinery oil (0.1 ppm). Lower metal contents of the
      pyrolytic oils reveal that pyrolysis of the waste machinery oils leads to the
      formation of environmental friendly pyrolytic oils with higher heating values.

PMID- 19744780
TI  - A novel ionic liquid/micro-volume back extraction procedure combined with flame
      atomic absorption spectrometry for determination of trace nickel in samples of
      nutritional interest.
AB  - A simple, highly sensitive and environment-friendly method for the determination
      of trace amount of nickel ion in different matrices is proposed. In the
      preconcentration step, the nickel from 10 mL of an aqueous solution was extracted
      into 500 microL of ionic liquid, 1-butyl-3-methylimidazolium hexafluorophosphate
      [C(4)MIM][PF(6)], containing PAN as complexing agent. Subsequently, the PAN
      complex was back-extracted into 250 microL of nitric acid solution, and 100
      microL of it was analyzed by flow injection flame atomic absorption spectrometry
      (FI-FAAS). The main parameter influencing the extraction and determination of
      nickel, such as pH, concentration of PAN, extraction time and temperature, ionic
      strength, and concentration of stripping acid solution, were optimized. An
      enhancement factor of 40.2 was achieved with 25 mL sample. The limit of detection
      (LOD) and quantification obtained under the optimum conditions were 12.5 and 41.0
      microg L(-1), respectively. To validate the proposed methods two certified
      reference materials 681-I and BCR No. 288 were analyzed and the results were in
      good agreement with the certified values. The proposed method was successfully
      applied to determination of nickel in water samples, rice flour and black tea.

PMID- 19744781
TI  - Physicochemical characterization of cement kiln dust for potential reuse in
      acidic wastewater treatment.
AB  - Cement kiln dust (CKD) is a fine-grained material produced during the manufacture
      of cement. Current reuse options are limited and the bulk of CKD not reused in
      the cement manufacturing process is sent to landfills or stored on-site. Due to
      the calcium oxide (CaO) content of CKD, it has the potential to be used as a
      replacement for lime in treating acidic wastewaters such as acid rock drainage
      (ARD). This paper outlines the results of an examination of the physical and
      chemical properties of CKD samples collected from six cement plants. The CKD
      samples were analyzed for major oxides using X-ray diffraction (XRD), available
      lime, specific surface area, particle size, and morphology using scanning
      electron microscope (SEM) and compared with a commercial quicklime product.
      Conductivity, pH, and calcium concentrations of slaked CKD and quicklime
      solutions were used as indicators of reactivity of the CKD. Slaking of two of the
      CKD samples with the highest free lime contents (e.g., 34 and 37% free CaO) gave
      elevated pH values statistically comparable to those of the commercial quicklime
      sample that was characterized as having 87% available CaO. Acid neutralization
      trials indicate that even CKD samples with low free lime contents could be
      effective at neutralizing acidic wastewaters.

PMID- 19744782
TI  - Polychlorinated biphenyls emission from a medical waste incinerator in China.
AB  - Detailed polychlorinated biphenyls (PCBs) congener patterns were determined in
      the flue gas from a medical waste incinerator (MWI) using high-resolution gas
      chromatograph coupled to high-resolution mass spectrometer (HRGC/HRMS). The total
      PCBs concentration of all homologues (mono- to deca-chlorinated homologues) in
      the flue gas ranged from 138.01 to 855.35 ng/Nm(3) and the WHO-TEQ value varied
      from 0.046 to 0.549 ng/Nm(3) under the different operating conditions. PCB-77
      concentration was the highest among dioxin-like PCBs and PCB-126 contributed
      mostly to the WHO-TEQ. The ratios of dioxin-like PCBs in the total PCB
      concentrations in the flue gas varied between 11.7% and 26.0% (the average value
      is 18.7%). Three inhibitors, sulfur, urea, and ammonium sulfate were tested to
      investigate the capacity for preventing PCBs formation. The decomposition
      efficiency for total PCBs and PCBs TEQ ranged from 38% to 84% and 69% to 92%
      respectively. It was shown that urea mixed with ammonium sulfate and more
      activated carbon was proved to be the most effective inhibitor for PCBs
      formation. The removal efficiencies (REs) of the total PCBs concentration and
      PCBs TEQ by the bag filter under two conditions were 69% and 85%, and 86% and 94%
      respectively.

PMID- 19744783
TI  - Equilibrium, kinetics and thermodynamic studies for sorption of chlorobenzenes on
      CTMAB modified bentonite and kaolinite.
AB  - The sorption of chlorobenzenes (CBs) by cetyltrimethylammonium bromide (CTMAB)
      modified bentonite and kaolinite was investigated. The sorption isotherms for CBs
      were nearly linear, suggesting that sorption could be described by a distribution
      process. The distribution coefficient (K(d)) was primarily affected by the amount
      of sorbed surfactant. The organic carbon normalized sorption coefficient (K(oc)),
      however, was particularly dependent on arrangement of the surfactant cations. The
      K(d) of CBs was larger for CTMAB-bentonites than that for CTMAB-kaolinites, while
      the case for K(oc) was opposite. Thus, the clay mineral structure and morphology
      had a considerable influence on the surfactant arrangement, which was responsible
      for the partitioning of CBs. The sorption of CBs onto both CTMAB-bentonites and
      CTMAB-kaolinites followed pseudo-second-order kinetics. The intra-particle
      diffusion model for sorption was also investigated and compared to identify
      sorption mechanism. The sorption of CBs both on CTMAB-bentonites and CTMAB
      kaolinites was exothermic in nature and accompanied by an increase in entropy and
      a decrease in Gibbs energy in the temperature range of 15-35 degrees C. The
      results indicated that CBs strongly interacted with CTMAB modified bentonite and
      kaolinite.

PMID- 19744784
TI  - An optical chemical sensor for thorium (IV) determination based on thorin.
AB  - A selective method for the determination of thorium (IV) using an optical sensor
      is described. The sensing membrane is prepared by immobilization of thorin
      methyltrioctylammonium ion pair on triacetylcellulose polymer. The sensor
      produced a linear response for thorium (IV) concentration in the range of 6.46 x
      10(-6) to 9.91 x 10(-5)mol L(-1) with detection limit of 1.85 x 10(-6)mol L(-1).
      The regeneration of optode was accomplished completely at a short time (less than
      20s) with 0.1 mol L(-1) of oxalate ion solution. The relative standard deviation
      for ten replicate measurements of 2.15 x 10(-5) and 8.62 x 10(-5)mol L(-1) of
      thorium was 2.71 and 1.65%, respectively. The optode membrane exhibits good
      selectivity for thorium (IV) over several other ionic species and are comparable
      to those obtained in case of spectrophotometric determination of thorium using
      thorin in solution. A good agreement with the ICP-MS and spiked method was
      achieved when the proposed optode was applied to the determination of thorium
      (IV) in dust and water samples.

PMID- 19744785
TI  - Novel negatively charged hybrids. 3. Removal of Pb2+ from aqueous solution using
      zwitterionic hybrid polymers as adsorbent.
AB  - Using zwitterionic hybrid polymers as adsorbent, the adsorption kinetics and
      isotherm, thermodynamic parameters of Delta G, Delta H and DeltaS for the removal
      of Pb(2+) from aqueous solution were investigated. It is indicated that the
      adsorption of Pb(2+) ions on these zwitterionic hybrid polymers followed the
      Lagergren second-order kinetic model and Freundlich isotherm model, demonstrating
      that the adsorption process might be Langmuir monolayer adsorption. The negative
      values of Delta G and the positive values of Delta H evidence that Pb(2+)
      adsorption on these zwitterionic hybrid polymers is spontaneous and endothermic
      process in nature. Moreover, the zwitterionic hybrid polymers produced reveal
      relatively higher desorption efficiency in 2 mol dm(-3) aqueous HNO(3) solution,
      indicating that they can be recycled in industrial processes. These findings
      suggest that these zwitterionic hybrid polymers are the promising adsorbents for
      Pb(2+) removal and can be potentially applied in the separation and recovery of
      Pb(2+) ions from the waste chemicals and contaminated water of lead-acid
      rechargeable battery.

PMID- 19744786
TI  - Acidic leaching and precipitation of zinc and manganese from spent battery
      powders using various reductants.
AB  - The main objective of this study was to investigate the effects of reductive
      acidic leaching and further precipitation on the recovery of manganese and zinc
      from spent alkaline and zinc-carbon battery powders. Ascorbic acid (AA), citric
      acid (CA) and oxalic acid (OA) were tested as the reductants. Sodium hydroxide
      and potassium hydroxide were used as precipitating agents. OA with H(2)SO(4) or
      HCl was not effective on the leaching of zinc due to the formation of zinc
      oxalate precipitates. However, the other reducing agents (CA and AA) tested under
      various experimental conditions were effective in the acidic leaching of both
      zinc and manganese. Leaching yields of both manganese and zinc were higher at
      leach temperature of 90 degrees C than those at 30 degrees C. Leach solutions
      were purified by the selective precipitation of manganese and zinc using KOH or
      NaOH. Complete precipitation was obtained for Mn at pH 9-10 and for Zn at pH 7-8.
      The use of ascorbic acid or citric acid as reductants in acidic leaching appears
      to be effective in the simultaneous leaching and further recovery of zinc and
      manganese from spent alkaline and zinc-carbon battery powders.

PMID- 19744787
TI  - Adsorption isotherm studies of chromium (VI) from aqueous solutions using sol-gel
      hydrotalcite-like compounds.
AB  - In under-developed countries, industries such as paint and pigment manufacturing,
      leather tanning, chrome plating and textile processing, usually discharge
      effluents containing Cr(VI) and Cr(III) into municipal sanitary sewers. It has
      been reported that Cr(VI) acts as a powerful epithelial irritant and as a human
      carcinogen. In the present work, hydrotalcite-like compounds with a Mg/Al ratio=2
      were synthesized by the sol-gel method. The hydrotalcite-like compounds and their
      corresponding thermally treated products were characterized by powder X-ray
      diffraction, infrared spectroscopy and N(2) adsorption. The hydrotalcite-like
      compounds and the heated solids were used as adsorbents for Cr(VI) in aqueous
      solutions. Adsorption isotherm studies of Cr(VI) from aqueous solution are
      described. The adsorbent capacity was determined using the Langmuir, Freundlich
      and Dubinin-Radushkevich adsorption isotherm models. The Cr(VI) adsorption
      isotherm data fit best to the Langmuir isotherm model. The maximum Cr(VI) uptake
      by hydrotalcite and the heated solids was determined using the Langmuir equation
      and was found to range between 26 and 29 mg Cr(VI)/g adsorbent.

PMID- 19744788
TI  - Security risk assessment: applying the concepts of fuzzy logic.
AB  - Chemical process industries (CPI) handling hazardous chemicals in bulk can be
      attractive targets for deliberate adversarial actions by terrorists, criminals
      and disgruntled employees. It is therefore imperative to have comprehensive
      security risk management programme including effective security risk assessment
      techniques. In an earlier work, it has been shown that security risk assessment
      can be done by conducting threat and vulnerability analysis or by developing
      Security Risk Factor Table (SRFT). HAZOP type vulnerability assessment sheets can
      be developed that are scenario based. In SRFT model, important security risk
      bearing factors such as location, ownership, visibility, inventory, etc., have
      been used. In this paper, the earlier developed SRFT model has been modified
      using the concepts of fuzzy logic. In the modified SRFT model, two linguistic
      fuzzy scales (three-point and four-point) are devised based on trapezoidal fuzzy
      numbers. Human subjectivity of different experts associated with previous SRFT
      model is tackled by mapping their scores to the newly devised fuzzy scale.
      Finally, the fuzzy score thus obtained is defuzzyfied to get the results. A test
      case of a refinery is used to explain the method and compared with the earlier
      work.

PMID- 19744789
TI  - Heavy metal pollution of coal mine-affected agricultural soils in the northern
      part of Bangladesh.
AB  - Total concentrations of heavy metals in the soils of mine drainage and
      surrounding agricultural fields in the northern part of Bangladesh were
      determined to evaluate the level of contamination. The average concentrations of
      Ti, Mn, Zn, Pb, As, Fe, Rb, Sr, Nb and Zr exceeded the world normal averages and,
      in some cases, Mn, Zn, As and Pb exceeded the toxic limit of the respective
      metals. Soil pollution assessment was carried out using enrichment factor (EF),
      geoaccumulation index (I(geo)) and pollution load index (PLI). The soils show
      significant enrichment with Ti, Mn, Zn, Pb, As, Fe, Sr and Nb, indicating inputs
      from mining activities. The I(geo) values have revealed that Mn (1.24+/-0.38), Zn
      (1.49+/-0.58) and Pb (1.63+/-0.38) are significantly accumulated in the study
      area. The PLIs derived from contamination factors indicate that the distal part
      of the coal mine-affected area is the most polluted (PLI of 4.02). Multivariate
      statistical analyses, principal component and cluster analyses, suggest that Mn,
      Zn, Pb and Ti are derived from anthropogenic sources, particularly coal mining
      activities, and the extreme proximal and distal parts are heavily contaminated
      with maximum heavy metals.

PMID- 19744790
TI  - Removal of hazardous metals from MSW fly ash--an evaluation of ash leaching
      methods.
AB  - Incineration is a commonly applied management method for municipal solid waste
      (MSW). However, significant amounts of potentially hazardous metal species are
      present in the resulting ash, and these may be leached into the environment. A
      common idea for cleaning the ash is to use enhanced leaching with strong mineral
      acids. However, due to the alkalinity of the ash, large amounts of acid are
      needed and this is a drawback. Therefore, this work was undertaken in order to
      investigate some alternative leaching media (EDTA, ammonium nitrate, ammonium
      chloride and a number of organic acids) and to compare them with the usual
      mineral acids and water. All leaching methods gave a significant increase in ash
      specific surface area due to removal of soluble bulk (matrix) compounds, such as
      CaCO(3) and alkali metal chlorides. The use of mineral acids and EDTA mobilised
      many elements, especially Cu, Zn and Pb, whereas the organic acids generally were
      not very effective as leaching agents for metals. Leaching using NH(4)NO(3) was
      especially effective for the release of Cu. The results show that washing of MSW
      filter ash with alternative leaching agents is a possible way to remove hazardous
      metals from MSW fly ash.

PMID- 19744791
TI  - Distortion corrections of ESI data cubes for magnetic studies.
AB  - Measuring magnetic properties at a nanometre scale could be achieved in a
      transmission electron microscope by using dedicated techniques. Among these, the
      energy-loss magnetic chiral dichroism has already proven its efficiency and needs
      improvements to be widely used. The energy spectrum imaging technique can be used
      to measure dichroism but some image treatments are necessary due to distortions.
      This paper deals with the corrections that need to be applied on the data to
      remove all distortions, especially drift and non-isochromaticity, and extract
      reliable information. The measure and correction procedures are developed on an
      artificial data cube containing the dichroic signal and some noise to prove the
      efficiency of the routines.

PMID- 19744792
TI  - In vivo evaluation of potential nematicidal properties of ethanol extract of
      Canthium mannii (Rubiaceae) on Heligmosomoides polygyrus parasite of rodents.
AB  - The nematicidal activity of ethanol extract (ETE) of Canthium mannii (Rubiaceae)
      was assessed in vivo compared to that of Mebendazole on the adult of
      Heligmosomoides polygyrus parasite of rodents. One hundred and five Swiss white
      mice of two sexes aged 5-6 weeks old, and weighing between 20 and 25 g were
      orally infected with a 0.8 ml of a dose of 104-120, 1-week-old H. polygyrus
      infective larvae (L(3)). After the pre-patent period (9-11 days), infected
      animals were randomly divided into 7 groups of 15 animals each. The nematicidal
      efficacy of the ETE was monitored through faecal egg count reduction (FECR) and
      total worm count reduction (TWCR). Five doses (350, 700, 1400, 2800 and 5600
      mgkg(-1) body weight) for ETE and 22 mgkg(-1) for Mebendazole were studied using
      a bioassay. Mebendazole and 3% dimethylsulfoxide (DMSO) were included in the
      assays as reference drug and placebo, respectively. Each host received according
      to its weight for 7 days a daily dose of 0.7ml of the product. The ETE for all
      the doses tested except the dose rate 350 mgkg(-1)bwt was active in vivo on the
      adult of H. polygyrus and reduced significantly (p<0.05) the FEC and the TWC of
      the nematode. The dose rate 5600 mgkg(-1)bwt showed the highest nematicidal
      activity of 75.0% FECR and 83.6% TWCR 7 days post-treatment. These results
      supported the possible use of medicinal plants in the control of gastro
      intestinal helminthiasis.

PMID- 19744793
TI  - Making sense of post-treatment surveillance in head and neck cancer: when and
      what of follow-up.
AB  - Follow-up in patients treated for head and neck cancer (HNC) is aimed at early
      detection of recurrence, metastases and second primary tumours. Various
      modalities for the routine follow-up of patients with HNC have been proposed and
      studied in the literature. Consequently, practising head and neck surgeons and
      oncologists all over the world use different guidelines and protocols to follow
      up their patients. These guidelines involve follow-up intervals of varying
      intensity and schedule an assortment of investigations that may be neither
      logical nor practical. This follow-up process may be difficult to administrate,
      cause unnecessary discomfort and morbidity to the patient and can have serious
      cost-implications to the healthcare system. This review summarises strategies for
      follow-up, imaging modalities and key investigations in the literature published
      between 1980 and 2009. In this structured review, we have assessed studies in the
      literature that have addressed follow-up intervals, imaging tests, tumour
      markers, endoscopy and thyroid function tests as a part of the routine post
      treatment surveillance in HNC patients. Studies analysing the cost benefit of
      such surveillance have also been addressed. Based on the evidence presented, we
      have compiled definitive recommendations for effective surveillance/post
      treatment follow-up in patients with HNC.

PMID- 19744794
TI  - Loneliness and cortisol: momentary, day-to-day, and trait associations.
AB  - In attempts to understand the social determinants of health, strong associations
      have been found between measures of loneliness, physiological stress processes,
      and physical and mental health outcomes. Feelings of loneliness are hypothesized
      to have implications for physiological stress processes, including activity of
      the hypothalamic-pituitary-adrenal (HPA) axis. In a community sample of young
      adults, multilevel modeling was used to examine whether trait and state feelings
      of loneliness were related to changes in levels of the stress-sensitive hormone
      cortisol, and whether the associations between loneliness and cortisol were
      mediated or moderated by the presence of concurrent depression or high levels of
      chronic life stress. Results indicated that trait loneliness was associated with
      a flattening of the diurnal cortisol rhythm. In addition, both daily and
      momentary state variations in loneliness were related to cortisol. Prior day
      feelings of loneliness were associated with an increased cortisol awakening
      response the next morning and momentary experiences of loneliness during the day
      were associated with momentary increases in cortisol among youth who also had
      high chronic interpersonal stress. Results were significant after covarying
      current depression, both chronic and momentary reports of stress, and medical and
      lifestyle covariates. This study expanded on prior work by investigating and
      revealing three different time courses of association between loneliness and HPA
      axis activity in young adults: trait, daily and momentary.

PMID- 19744795
TI  - Sex differences in the self-administration of cannabinoids and other drugs of
      abuse.
AB  - Many studies have provided evidence for important sex-dependent differences in
      the origins, outcomes and treatment of drug abuse and dependence. Preclinical
      studies typically have employed animal models of addiction, such as oral or
      intravenous self-administration, to untangle the environmental, neurobiological
      and genetic factors that contribute to the shift from occasional, recreational
      use to compulsive, uncontrolled intake of drugs. Craving and relapse of drug
      seeking in abstinent individuals have also been found to differ between men and
      women. Identification of the neurobiological basis of craving and drug dependence
      continues to pose a challenge to addiction research. Significant sex differences
      are emerging in substance-abuse-related behavior, which has increased the demand
      for research on how drug consumption may have different causes, progression and
      consequences in men and women. In keeping with epidemiological data in humans,
      differences between the two sexes in drug seeking and intake have been well
      documented in animal studies, with most recent findings related to abuse of
      cannabinoids. Clinical and preclinical findings indicate that sex and gonadal
      hormones may account for individual differences in susceptibility to the
      reinforcing effects of addictive substances, and that differences in
      vulnerability to drug abuse may be mediated by the same biological mechanisms.
      This review focuses on the differences between males and females in relation to
      drug self-administration and how such behavior may be affected by hormonal
      status.

PMID- 19744796
TI  - The role of coping in moderating within-day associations between negative
      triggers and substance use cravings: a daily diary investigation.
AB  - To address the lack of research examining within-person processes associated with
      the maintenance of abstinence from substance use, this study examines both
      associations between negative affect and social experiences and same-day levels
      of substance use cravings among college students in 'Twelve-Step' substance abuse
      recovery and the role of coping strategies in moderating these within-day
      associations. The sample consisted of 1222 end-of-day reports made by 55
      recovering college students, 39 males and 16 females. Findings include that daily
      cravings were predicted by same-day negative affect and each of four negative
      social experiences. Moreover, each of these within-day associations was moderated
      by individuals' levels of avoidance coping. In contrast, problem-solving coping
      only moderated the associations between negative affect and cravings. These
      findings document a within-day mechanism through which coping strategies,
      especially avoidance coping, may influence daily variation in cravings and in
      turn affect abstinence.

PMID- 19744797
TI  - Schizophrenia, sleep disturbances and the suprachiasmatic nucleus: reduced nitric
      oxide synthase may matter.

PMID- 19744798
TI  - Nervous system in the gluten syndrome: a close relationship.

PMID- 19744799
TI  - Antiangiogenesis therapy might have the unintended effect of promoting tumor
      metastasis by increasing an alternative circulatory system.
AB  - Antiangiogenesis therapy is one of the most promising approaches to cancer
      treatment. Its clinical success has come out but still too limited.
      Vascularization of tumor is a complex and heterogenous process. So far, it has
      been demonstrated that several additional mechanisms can provide the tumor with
      oxygen and nutrients. Moreover, it is now clear that vascularization of tumor
      does not necessarily depend on endothelial cells proliferation and sprouting of
      new capillaries. Vasculogenic mimicry (VM) as an alternative circulatory system,
      has been described in multiple malignant tumor types, and considered to be
      associated with a poor prognosis for the patient. VM serves as an adjunct to the
      existing vasculature system, thereby aiding tumor growth as well as contributing
      to the metastatic process. Moreover, hypoxia has been confirmed to promote some
      tumor cells to form vessel-like tubes in vitro and express genes associated with
      VM. Yet, the current antiangiogenesis strategies, which are directed mainly
      against the tumor endothelium and then cause hypoxia of tumor cells, have no
      effect on VM. Our central hypothesis is that when the endothelium-dependent
      vessels are inhibited by the effective angiogenesis inhibitors, the hypoxia of
      tumor cells caused by antiangiogenesis may increase VM compensatively which can
      replace the job of endothelium-dependent vessels to maintain the tumor blood
      supply and provide a convenient route of tumor metastasis. As a result,
      antiangiogenesis therapy might have the unintended effect of promoting tumor
      metastasis by increasing VM. Thus, treatment strategies that target the tumor
      microcirculation should not only target endothelium-dependent vessels, but also
      take VM into account in tumors presenting VM.

PMID- 19744800
TI  - Predictors of prostate cancer-specific mortality in elderly men with intermediate
      risk prostate cancer treated with brachytherapy with or without external beam
      radiation therapy.
AB  - PURPOSE: To identify clinical factors associated with prostate cancer-specific
      mortality (PCSM), adjusting for comorbidity, in elderly men with intermediate
      risk prostate cancer treated with brachytherapy alone or in conjunction with
      external beam radiation therapy. METHODS AND MATERIALS: The study cohort
      comprised 1,978 men of median age 71 (interquartile range, 66-75) years with
      intermediate-risk disease (Gleason score 7, prostate-specific antigen (PSA) 20
      ng/mL or less, tumor category T2c or less). Fine and Gray's multivariable
      competing risks regression was used to assess whether prevalent cardiovascular
      disease (CVD), age, treatment, year of brachytherapy, PSA level, or tumor
      category was associated with the risk of PCSM. RESULTS: After a median follow-up
      of 3.2 (interquartile range, 1.7-5.4) years, the presence of CVD was
      significantly associated with a decreased risk of PCSM (adjusted hazard ratio,
      0.20; 95% CI 0.04-0.99; p = 0.05), whereas an increasing PSA level was
      significantly associated with an increased risk of PCSM (adjusted hazard ratio
      1.14; 95% CI 1.02-1.27; p = 0.02). In the absence of CVD, cumulative incidence
      estimates of PCSM were higher (p = 0.03) in men with PSA levels above as compared
      with the median PSA level (7.3 ng/mL) or less; however, in the setting of CVD
      there was no difference (p = 0.27) in these estimates stratified by the median
      PSA level (6.9 ng/mL). CONCLUSIONS: In elderly men with intermediate-risk
      prostate cancer, CVD status is a negative predictor of PCSM and affects the
      prognostic capacity of pretreatment PSA level. These observations support the
      potential utility of prerandomization stratification by comorbidity to more
      accurately assess prognostic factors and treatment effects within this
      population.

PMID- 19744801
TI  - Concurrent chemoradiotherapy with 5-fluorouracil and mitomycin C for invasive
      anal carcinoma in human immunodeficiency virus-positive patients receiving highly
      active antiretroviral therapy.
AB  - PURPOSE: To report the clinical outcomes of chemoradiotherapy (CRT) for anal
      carcinoma in human immunodeficiency virus (HIV)-infected patients receiving
      highly active antiretroviral therapy. PATIENTS AND METHODS: Between 1997 and
      2008, 21 HIV-positive patients who were receiving highly active antiretroviral
      therapy were treated with CRT (50.4 Gy at 1.8 Gy/fraction plus a 5.4-10.8-Gy
      external boost; 5-fluorouracil, 1,000 mg/m(2), Days 1-4 and 29-32; and mitomycin
      C, 10 mg/m(2), Days 1 and 29). A retrospective analysis was performed with
      respect to the tumor response, local control, cancer-specific and overall
      survival, and toxicity. The immunologic parameters, including pre- and post
      treatment CD4 count, viral load, and acquired immunodeficiency syndrome-specific
      morbidity was recorded during follow-up (median, 53 months; range, 10-99).
      RESULTS: CRT could be completed in all 21 patients with a reduction in the
      chemotherapy dose and/or interruption of radiotherapy in 5 and 5 cases,
      respectively. Acute Grade 3 toxicity occurred in 8 (38%) of the 21 patients. A
      complete response was achieved in 17 patients (81%), and tumor persistence or
      early progression was noted in 4 (19%). Six patients (29%) died, 5 of cancer
      progression and 1 of treatment-related toxicity. The 5-year local control, cancer
      specific, and overall survival rate was 59%, 75%, and 67%, respectively. The
      median CD4 count significantly decreased from 347.5 cells/microL before CRT to
      125 cells/microL 3-7 weeks after CRT completion (p <.001). In 6 (32%) of 19
      patients, an increase of the HIV viral load was noted. Both parameters returned
      to the pretreatment values with additional follow-up. CONCLUSION: Our data have
      confirmed that in the highly active antiretroviral therapy era, HIV-related anal
      cancer can be treated with standard CRT without dose reductions. Close
      surveillance of the immunologic parameters is necessary.

PMID- 19744802
TI  - Radiochemotherapy with cetuximab, cisplatin, and amifostine for locally advanced
      head and neck cancer: a feasibility study.
AB  - PURPOSE: Radiotherapy (RT) combined with cisplatin or cetuximab is the standard
      of care for patients with locally advanced head/neck cancer (LA-HNC). The
      feasibility of radiochemotherapy with cisplatin and cetuximab, supported with
      amifostine, was herein investigated. METHODS AND MATERIALS: Forty-three patients
      with LA-HNC were recruited. Conformal hypofractionated/accelerated RT with
      amifostine cytoprotection (2.7 Gy/fraction, 21 fractions in 4 weeks) was combined
      with cisplatin (30 mg/m(2)/week) and cetuximab (standard weekly regimen) therapy.
      The dose of amifostine was individualized according to tolerance. RESULTS: A high
      daily amifostine dose (750-1,000 mg) was tolerated by 41.8% of patients, and a
      standard dose (500 mg) was tolerated by 34.9% of patients. A high amifostine dose
      was linked to reduced RT delays (p = 0.0003). Grade 3 to 4 (3-4) mucositis
      occurred in 7/43 (16.2%) patients, and fungal infections occurred in 18/43
      (41.8%) patients. Radiation dermatitis was not aggravated. Interruption of
      cetuximab due to acneiform rash was necessary in 23.3% of patients, while
      amifostine-related fever and rash were not observed. Severe late radiation
      sequelae consisted of laryngeal edema (9% laryngeal cases) and cervical
      strictures (33% of hypopharyngeal cases). Good salivary function was preserved in
      6/11 (54.5%) nasopharyngeal cancer patients. The complete response rate was
      68.5%, reaching 77.2% in patients with minor radiotherapy delays. The 24-month
      local control and survival rates were 72.3% and 91%, respectively (median follow
      up was 13 months.). CONCLUSIONS: In this feasibility study, weekly administration
      of cisplatin and cetuximab was safely combined with accelerated RT, supported
      with amifostine, at the cost of a high incidence of acneiform rash but a reduced
      incidence of amifostine-related fever/rash. A high daily dose of amifostine
      allows completion of therapy with minor delays.

PMID- 19744803
TI  - The carpometacarpal stress view radiograph in the evaluation of
      trapeziometacarpal joint laxity.
AB  - PURPOSE: Hypermobility at the thumb carpometacarpal (CMC) joint has been proposed
      as an explanation for abnormal loading and subsequent development of
      osteoarthritis. Radiographic evaluation of this joint is difficult owing to the
      obliquity of the articulation. We modified a previously described technique to
      obtain a bilateral stress radiograph of the thumbs to measure CMC joint laxity.
      The purpose of this study was to present the details of this modified technique
      and evaluate its reproducibility in a group of volunteer subjects. We
      hypothesized that this technique would be reliable and reproducible. METHODS: A
      posteroanterior radiograph was obtained after asking volunteer subjects to press
      their thumbs together using a foam hand support. Three measurements were
      performed: radial subluxation of the first metacarpal base, first metacarpal
      articular width, and the distance between the ulnar articular facet of the
      trapezium and the ulnar metacarpal edge (uncovered edge). Using digital
      calibration on a picture archiving and communication system radiology server, a
      radiologist, radiology resident, orthopedic surgeon, and orthopedic resident
      performed measurements at 2 time points. To evaluate consistency among the
      raters, intraclass correlation coefficients were calculated. Test-retest
      bivariate analyses were performed to assess intra-rater reliability. RESULTS: A
      total of 69 volunteers (39 women and 30 men) were imaged. Women showed
      significantly greater radial subluxation compared to men (p < .01). Inter-rater
      reliability coefficients for radial subluxation and articular width initially and
      at 2 weeks showed high agreement, as did test-retest reliability coefficients.
      For the uncovered edge measurement, inter-rater reliability coefficients were
      low, with wide variation in reliability. CONCLUSIONS: The modified thumb CMC
      stress view radiograph evaluates laxity and joint abnormalities of the
      trapeziometacarpal articulation. The details of the radiographic technique are
      straightforward, and the inter- and intra-observer reliability of radial
      subluxation and first metacarpal width are high. The ratio of the 2 measurements
      provides an accurate measure of the radiographic subluxation of the first
      metacarpal from the trapezium. This measurement is most specific to radial
      subluxation under simulated active loading, in the plane of the hand. The medial
      uncovered edge of trapezium measurement does not have high inter-observer
      reliability and varies widely, and it should not be included in laxity
      measurements.

PMID- 19744804
TI  - [Lipschutz acute genital ulcer].
AB  - Lipschutz acute genital ulcer is a rare distinctive cause of nonvenereal acute
      genital ulcers that occurs particularly in adolescents described in 1913. We
      report here a typical case that occurred in a 24-year-old virgin woman who
      developed flu-like symptoms and painful genital ulcers that healed spontaneously
      within a week and without any infection (Epstein Barr Virus, toxoplasmosis,
      salmonella). The physiopathogeny remains unknown. However, there are body of
      evidences pointing out a possible link to several nonvenereal infections,
      including mainly Epstein-Barr virus acute infection. This rare benign but
      disabling entity should be known by gynecologists.

PMID- 19744805
TI  - Risk management and post-marketing surveillance of CNS drugs: an introduction.

PMID- 19744806
TI  - Lack of transmission of methicillin-resistant Staphylococcus aureus (MRSA)
      between apparently healthy dogs in a rescue kennel.
AB  - Although it is widely accepted that methicillin-resistant Staphylococcus aureus
      (MRSA) can be transmitted between humans and animals in both directions, little
      is known about the dynamics of animal-to-animal transfer. This study aimed to
      investigate aspects of dog-to-dog MRSA transfer in a rescue facility in the South
      East of England during an MRSA outbreak. One hundred and twenty-nine apparently
      healthy dogs, mostly housed in pairs, were swabbed at nasal, oral, axillary and
      perianal sites. Swabs were enriched in selective broth and staphylococci
      identified using standard biological methods. MRSA isolates were confirmed by
      demonstration of the thermonuclease gene (nuc) and mecA. After initial swabbing,
      a dog excluded from the study design but housed at the same facility was
      discovered to have a wound infection due to MRSA. MRSA carriage was identified in
      10/129 dogs (7.8%) and all isolates were of the same lineage as the one isolated
      from the infected dog. All carrier dogs lived in shared kennels and their 16
      kennel partners sampled negative on two occasions. Concurrently with successful
      antimicrobial treatment of the infected patient, MRSA carriage resolved
      spontaneously in all dogs within two weeks. In conclusion, MRSA did not transmit
      readily between apparently healthy dogs, MRSA carriage was not supported for long
      periods in a regularly cleaned environment and exposure alone may not lead to
      MRSA acquisition by dogs without the presence of additional risk factors.

PMID- 19744807
TI  - Heat shock protein patterns in the bovine ovary and relation with cystic ovarian
      disease.
AB  - The present study was performed to determine how the development of cystic
      ovarian disease (COD) affecting the ovarian expression of heat shock proteins
      (HSP) in cows were expressing extrous cycles. HSP27, HSP60, HSP70 and HSP90 were
      evaluated in different ovarian components by Western blot and semiquantitative
      immunohistochemical analysis. Greater expression of the HSP27 gene was detected
      in the granulosa and theca cells of primary, secondary, tertiary and cystic
      follicles, with decreasing amount in atretic follicles. HSP60, HSP70 and HSP90
      showed a similar pattern of immunostaining, with moderate gene expression in
      primary and secondary follicles, increased expression in tertiary and atretic
      follicles with the greatest gene expression in cystic follicles. HSP were also
      localized in the corpus luteum, corpus albicans, interstitial tissue and tunica
      albuginea. The relative amount of protein in the follicular wall of small and
      large healthy follicles and cystic follicles as analysed by Western immunoblot
      was consistent with the immunohistochemical data. We speculate that altered
      expression of HSP genes decreases apoptosis in the follicular wall and leads to
      the delayed regression of cystic follicles. This study supports earlier
      observations suggesting that aberrant HSP gene expression, observed in cells of
      the cystic follicles, is probably associated with the intra-ovarian component of
      COD pathogenesis.

PMID- 19744808
TI  - Odontometric sex assessment in Indians.
AB  - Sex determination of unidentified skeletal remains is important and various hard
      tissue parameters have been evaluated towards this end. The dentition is
      considered as a useful adjunct in skeletal sex determination, particularly since
      teeth are resistant to postmortem destruction and fragmentation. Sex dimorphism
      in tooth size and the accuracy of odontometric sex prediction, is found to vary
      in different regions and researchers have advocated the need for population
      specific data. No odontometric standards exist for Indians for use in forensic
      sex prediction. Therefore, this study examined sexual dimorphism in Indians using
      univariate and multivariate statistics. Mesiodistal (MD) and buccolingual (BL)
      measurements of all teeth, except third molars, were obtained on dental casts of
      [corrected] 105 Indians (52 females, 53 males). The canines were [corrected]
      found to be the most dimorphic tooth, followed by the [corrected] BL dimensions
      of [corrected]first molars and that of mandibular second premolars. In general,
      mandibular teeth and BL dimensions showed greater tendency to be larger in males.
      However, just over a quarter of the measured variables (16/56; 28.6%) were
      statistically larger in males (p < 0.05). Moreover, ten tooth variables exhibited
      reverse dimorphism, i.e. female dimensions were larger than those of males.
      Stepwise discriminant function analysis revealed moderate accuracy in sex
      prediction: the teeth from both jaws taken together were able to determine sex to
      higher levels (76.2%) compared to only mandibular teeth (72.4%) or only maxillary
      teeth (67.6%). Interestingly, teeth that contributed to the stepwise discriminant
      analysis were either statistically larger in males or exhibited reverse
      dimorphism, indicating that such tooth variables may have better ability to
      correctly identify sex. [corrected]

PMID- 19744809
TI  - Detection of local recurrences of limb soft tissue sarcomas: is magnetic
      resonance imaging (MRI) relevant?
AB  - The role of systematic magnetic resonance imaging (MRI) after resection of soft
      tissue sarcomas (STS) of the limb is opened to debate. The aim of our study was
      to retrospectively evaluate the effectiveness of a systematic MRI examination
      performed in 124 adult patients treated between 1996 and 2006 for a non
      metastatic limb STS at our centre: 86 patients (70%) had clear resection margins
      (R0) and 111 patients (90%) received an adjuvant radiotherapy. Among the 11 local
      recurrences (9%) which were observed, MRI was able to detect only 2 asymptomatic
      local recurrences, one with and one without synchronous metastasis. Both had
      microscopically involved margins (R1). In contrast, MRI showed 11 false positive
      cases. As the predictive positive value of MRI was 42%, clinical follow-up seems
      to be more effective. As observed in our study, systematic MRI examination is not
      relevant for the follow-up of all limb soft tissue sarcomas. A prospective study
      could be promoted to evaluate the role of MRI in patients at high risk of local
      recurrence.

PMID- 19744810
TI  - A direct LC/MS/MS method for the determination of ciclopirox penetration across
      human nail plate in in vitro penetration studies.
AB  - Due to severe chelating effect caused by N-hydroxylpyridone group of ciclopirox,
      there is no published direct HPLC or LC/MS/MS method for the determination of
      ciclopirox in any in vitro or in vivo matrix. Instead, the time-consuming pre
      column derivatization methods have been adapted for indirect analysis of
      ciclopirox. After overcoming the chelating problem by using K(2)EDTA coated
      tubes, a direct, sensitive and high-throughput LC/MS/MS method was successfully
      developed and validated to determine the amount of ciclopirox that penetrated
      across the nail plate during in vitro nail penetration studies. The method
      involved adding a chemical analog, chloridazon as internal standard (IS) in
      K(2)EDTA coated tubes, mixing IS with ciclopirox in a 96-well plate and then
      proceeding to LC/MS/MS analysis. The MS/MS was selected to monitor m/z 208.0-
      >135.8 and 221.8-->77.0 for ciclopirox and IS, respectively, using positive
      electrospray ionization. The method was validated over a concentration range of 8
      256 ng/mL, yielding calibration curves with correlation coefficients greater than
      0.9991 with a lower limit of quantitation (LLOQ) of 8 ng/mL. The assay precision
      and accuracy were evaluated using quality control (QC) samples at three
      concentration levels. Analyzed concentrations ranged from 101% to 113% of their
      respective nominal concentration levels with coefficients of variation (CV) below
      10.6%. The average recovery of ciclopirox from nail matrix was 101%. The
      validated method was successfully used to analyze the ciclopirox formulation and
      in vitro nail penetration samples.

PMID- 19744811
TI  - Novel, dynamic on-line analytical separation system for dissolution of drugs from
      poly(lactic acid) nanoparticles.
AB  - A novel method for investigating drug release in a dynamic manner from
      nanoparticles including, but not limited to, biodegradable poly(lactic acid)
      (PLA) is reported. The PLA nanoparticles were prepared by the nanoprecipitation
      method. Two poorly soluble drugs, beclomethasone dipropionate (BDP) and
      indomethacin, were encapsulated into PLA nanoparticles, and their dissolution
      from the nanoparticles were followed in a dynamic way. The on-line method
      comprised a short column (vessel) packed with the PLA nanoparticles, on-line
      connected to an analytical liquid chromatographic column via a multiport
      switching valve equipped with two loops. The system allowed monitoring of the
      drug release profiles in real time, and the conditions for the drug release could
      be precisely controlled and easily changed. The effects of solvent composition
      and temperature on the rate of dissolution of the drugs from the PLA
      nanoparticles were investigated. The system proved to be linear for the drugs
      tested over the concentration range 10-3000 ng (n=6, R(2)=0.999 and 0.997 for
      indomethacin and beclomethasone, respectively) and repeatable (RSD of peak areas
      <0.5%). The recoveries of the dissolution study were quantitative (120 and 103%
      for indomethacin and beclomethasone, respectively).

PMID- 19744812
TI  - Requiem for "non-urgent" patients in the emergency department.

PMID- 19744813
TI  - Re: Peter Rosen's recent piece.

PMID- 19744816
TI  - Risk factors for longer term psychological distress in well-functioning
      fibromyalgia patients: a prospective study into prognostic factors.
AB  - OBJECTIVE: Psychological distress is a key risk factor for long-term complaints
      in fibromyalgia (FM). Prognostic factors for psychological distress might
      facilitate an early identification of patients at risk to help prevent long-term
      dysfunction, especially for the relatively well-functioning patients showing
      little distress who are usually not considered for treatment. This study hence
      examines potential prognostic factors in this subgroup. METHODS: Psychological
      distress, physical functioning, illness cognitions (helplessness, acceptance),
      pain-avoidance factors (passive pain-coping, fear of pain, hypervigilance), and
      social factors (social support, social reinforcement) was assessed in 78 low
      distress FM patients at baseline and after a mean of 9 months (SD=3.3). RESULTS:
      Baseline physical functioning did not predict changes in psychological distress,
      whereas a higher level of hypervigilance, less acceptance, and less perceived
      social support predicted an increase in psychological distress at follow-up.
      CONCLUSION: Illness cognitions, pain-avoidance factors, and social support can be
      considered as prognostic factors predicting changes in psychological distress in
      FM. More research is needed to investigate additional factors that could also be
      implicated (e.g. personality factors, stressful events). PRACTICE IMPLICATIONS:
      Timely assessment of illness cognitions, pain-avoidance factors, and social
      support may help identify subgroups of relatively well-functioning FM patients at
      risk of longer term aggravated psychological distress.

PMID- 19744817
TI  - The effects of Internet or interactive computer-based patient education in the
      field of breast cancer: a systematic literature review.
AB  - OBJECTIVE: The aim of this systematic review was to analyze what kind of Internet
      or interactive computer-based patient education programs have been developed and
      to analyze the effectiveness of these programs in the field of breast cancer
      patient education. Patient education for breast cancer patients is an important
      intervention to empower the patient. However, we know very little about the
      effects and potential of Internet-based patient education in the empowerment of
      breast cancer patients. METHODS: Complete databases were searched covering the
      period from the beginning of each database to November 2008. Studies were
      included if they concerned patient education for breast cancer patients with
      Internet or interactive computer programs and were based on randomized
      controlled, on clinical trials or quasi-experimental studies. RESULTS: We
      identified 14 articles involving 2374 participants. The design was randomized
      controlled trial in nine papers, in two papers clinical trial and in three quasi
      experimental. Seven of the studies were randomized to experimental and control
      groups, in two papers participants were grouped by ethnic and racial differences
      and by mode of Internet use and three studies measured the same group pre- and
      post-tests after using a computer program. The interventions used were described
      as interactive computer or multimedia programs and use of the Internet. The
      methodological solutions of the studies varied. The effects of the studies were
      diverse except for knowledge-related issues. Internet or interactive computer
      based patient education programs in the care of breast cancer patients may have
      positive effect increasing breast cancer knowledge. CONCLUSION: The results
      suggest a positive relationship between the Internet or computer-based patient
      education program use and the knowledge level of patients with breast cancer but
      a diverse relationship between patient's participation and other outcome
      measures. PRACTICE IMPLICATIONS: There is need to develop and research more
      Internet-based patient education.

PMID- 19744818
TI  - [Chronic pain after surgery].
AB  - The frequency of chronic postsurgical pain is high, ranging from 10 to 80%. Among
      the factors promoting it are the existence of preoperative pain, the intensity
      and duration of postoperative pain, and the type of surgery. It frequently has a
      neuropathic aspect. Because intraoperative nerve injuries are commonly associated
      with severe postoperative pain, and as neuropathic and inflammatory pain share
      neuroplasticity mechanisms, it is usually difficult to know which is responsible
      for the development of these mechanisms after surgery. Few studies have thus far
      evaluated methods for preventing chronic postsurgical pain, and their results are
      conflicting. Recent studies indicate, however, that the use of perioperative
      regional analgesia is associated with a reduced incidence of chronic postsurgical
      pain, compared with patient-controlled intravenous morphine. Antihyperalgesic
      drugs, such as NMDA antagonists, may also decrease chronic postsurgical pain by
      reducing its perioperative hyperalgesic component.

PMID- 19744819
TI  - [The Internet and shared decision-making between patients and healthcare
      providers].
AB  - Insurance companies like Kaiser Permanente in the United States remunerate
      physicians for their email correspondence with patients, increasing the
      efficiency of office visits. A survey by the French National Board of Physicians
      regarding the computerization of medical practices in April 2009, confirms that
      both physicians and patients in France are very favorable to the development of
      these tools. When patients can manage and/or access their medical files and
      determine which providers can access them, they become a true partner.

PMID- 19744820
TI  - [Medicine 2.0: the stakes of participatory medicine].
AB  - Web 2.0: interactive, collaborative tools (wikis, social networks, blogs, virtual
      worlds) make Internet users active participants rather than simple consumers.
      Medicine 2.0: mentalities, approaches, and medical practices are changing, thanks
      to greater access to information, communal exchanges, and the comparison of
      personal experiences. Beyond the many wikis, blogs, and other collaborative
      tools, the site PatientsLikeMe.com stands out from the 2.0 crowd by its graphic
      representation of the clinical results entered by patients. Various European Web
      2.0 sites exist as well. The risks reside in the reliability of information and
      the privacy of patient data. The challenges are to use these new resources to
      improve the quality of care and participate in the profound change they are
      bringing to the healthcare system.

PMID- 19744821
TI  - [Legal aspects of Web 2.0 in the health field].
AB  - Web 2.0 sites are considered to be hosting providers and not publishers of user
      generated content. The liability of hosting providers' liability is defined by
      the law enacted on June 21, 2004, on confidence in the digital economy. Hosting
      providers must promptly remove the information they host or make its access
      impossible once they are informed of its illegality. They are required to obtain
      and retain data to enable identification of any person who has contributed to
      content hosted by them. The liability of hosting providers has arisen in numerous
      disputes about user-produced content in various situations (discussion lists,
      blogs, etc.). The National Board of Physicians has developed specific ethical
      guidelines for web sites devoted to health issues and specifically for physician
      authored content. The National Board of Physicians acknowledges that physicians
      can present themselves, their office, and their specific practice on their web
      site, notwithstanding any restrictions otherwise applicable to advertising.

PMID- 19744822
TI  - [Contact dermatitis to nickel related to cellular phone use].

PMID- 19744823
TI  - Spontaneous cutaneous cholesterol embolism.

PMID- 19744824
TI  - Quantifying the magnitude of risk for balance impairment on falls in community
      dwelling older adults: a systematic review and meta-analysis.
AB  - OBJECTIVES: To evaluate and summarize the evidence linking balance impairment as
      a risk factor for falls in community-dwelling older adults. STUDY DESIGN AND
      SETTING: Systematic review and meta-analysis. English language articles in
      MEDLINE, EMBASE, CINAHL (1988-2009), under keywords of accidental falls, aged,
      risk factors, and hip, radius, ulna, and humerus fractures; and bibliographies of
      retrieved articles. Community-dwelling older adults in a prospective study, at
      least 1-year duration, age more than 60 years, and samples not specific to a
      single disease-defined population were included. Sample size, inclusion/exclusion
      criteria, demographics, clinical balance measurement scale, type of fall outcome,
      method of fall ascertainment, length of follow-up, and odds ratio (OR) or risk
      ratio (RR) were extracted. Studies must have reported adjustment for confounders.
      Random effects meta-analysis to generate summary risk estimate was used. A priori
      evaluation of sources of heterogeneity was performed. RESULTS: Twenty-three
      studies met the selection criteria. A single summary measure could not be
      calculated because of the nonequivalence of the OR and RR, producing an overall
      fall risk of RR of 1.42 (1.08, 1.85) and OR of 1.98 (1.60, 2.46). CONCLUSIONS:
      Balance impairment imparts a moderate increase on fall risk in community-dwelling
      older adults. The type of fall outcome, the length of follow-up, and the balance
      measurement tool impact the magnitude of the association. Specific balance
      measurement scales were identified with associations for an increased fall risk,
      but further research is required to refine recommendations for their use in
      clinical practice.

PMID- 19744825
TI  - Decreased accuracy in interpretation of community-based screening mammography for
      women with multiple clinical risk factors.
AB  - OBJECTIVE: To assess the impact of women's breast cancer risk factors (use of
      hormone therapy, family history of breast cancer, previous breast biopsy) on
      radiologists' mammographic interpretive performance and whether the influence of
      risk factors varies according to radiologist characteristics. STUDY DESIGN AND
      SETTING: Screening mammograms (n=638,947) performed from 1996 to 2005 by 134
      radiologists from three Breast Cancer Surveillance Consortium registries was
      linked to cancer outcomes, radiologist surveys, and patient questionnaires.
      Interpretive performance measures were modeled using marginal and conditional
      logistic regression. RESULTS: Having one or more clinical risk factors was
      associated with higher recall rates (1 vs. 0 risk factors: odds ratio [OR]=1.17,
      95% confidence interval [CI]=1.15-1.19; > or = 2 vs. 0: OR=1.43, 95% CI=1.40
      1.47) and lower specificity (1 vs. 0: OR=0.86 [95% CI=0.84-0.88]; > or = 2 vs. 0:
      OR=0.70 [95% CI=0.68-0.72]) without a corresponding improvement in sensitivity
      and only a small increase in positive predictive value (1 vs. 0: OR=1.08 [95%
      CI=0.99-1.19]; > or = 2 vs. 0: OR=1.12 [95% CI=0.99-1.26]). There was no
      indication that influence of risk factors varied by radiologist characteristics.
      CONCLUSION: Women with clinical risk factors who undergo screening mammography
      are more likely recalled for false-positive evaluation without an associated
      increase in cancer detection. Radiologists and patients with risk factors should
      be aware of this increased risk of adverse screening events.

PMID- 19744826
TI  - PET image reconstruction: A stopping rule for the MLEM algorithm based on
      properties of the updating coefficients.
AB  - An empirical stopping criterion for the 2D-maximum-likelihood expectation
      maximization (MLEM) iterative image reconstruction algorithm in positron emission
      tomography (PET) has been proposed. We have applied the MLEM algorithm on Monte
      Carlo generated noise-free projection data and studied the properties of the
      pixel updating coefficients (PUC) in the reconstructed images. Appropriate
      fitting lead to an analytical expression for the parameterization of the minimum
      value in the PUC vector for all non-zero pixels for a given number of detected
      counts, which can be employed as basis for the stopping criterion proposed. These
      results have been validated with simulated data from real PET images.

PMID- 19744827
TI  - The role of chemokines in the recruitment of lymphocytes to the liver.
AB  - Chemokines direct leukocyte trafficking and positioning within tissues. They thus
      play critical roles in regulating immune responses and inflammation. The
      chemokine system is complex involving interactions between multiple chemokines
      and their receptors that operate in combinatorial cascades with adhesion
      molecules. The involvement of multiple chemokines and chemokine receptors in
      these processes brings flexibility and specificity to recruitment. The hepatic
      vascular bed is a unique low flow environment through which leukocyte are
      recruited to the liver during homeostatic immune surveillance and in response to
      infection or injury. The rate of leukocyte recruitment and the nature of cells
      recruited through the sinusoids in response to inflammatory signals will shape
      the severity of disease. At one end of the spectrum fulminant liver failure
      results from a rapid recruitment of leukocytes that leads to hepatocyte
      destruction and liver failure at the other diseases such as chronic hepatitis C
      infection may progress over many years from hepatitis to fibrosis and cirrhosis.
      Chronic hepatitis is charactezised by a T lymphocyte rich infiltrate and the
      nature and outcome of hepatitis will depend on the T cell subsets recruited,
      their activation and function within the liver. Different subsets of effector T
      cells have been described based on their secretion of cytokines and specific
      functions. These include Th1 and Th2 cells and more recently Th17 and Th9 cells
      which are associated with different types of immune response and which express
      distinct patterns of chemokine receptors that promote their recruitment under
      particular conditions. The effector function of these cells is balanced by the
      recruitment of regulatory T cells that are able to suppress antigen-specific
      effectors to allow resolution of immune responses and restoration of immune
      homeostasis. Understanding the signals that are responsible for recruiting
      different lymphocyte subsets to the liver will elucidate disease pathogenesis and
      open up new therapeutic approaches to modulate recruitment in favour of
      resolution rather than injury.

PMID- 19744828
TI  - Association of T-cell reactivity with beta-cell function in recent onset type 1
      diabetes patients.
AB  - OBJECTIVE: The aim of the current study was to investigate whether autoantigen
      directed T-cell reactivity relates to beta-cell function during the first 78
      weeks after diagnosis of type 1 diabetes. RESEARCH DESIGN AND METHODS: 50 adults
      and 49 children (mean age 27.3 and 10.9 years respectively) with recent onset
      type 1 diabetes who participated in a placebo-controlled trial of immune
      intervention with DiaPep277 were analyzed. Secretion of interferon (IFN)-gamma,
      interleukin (IL)-5, IL-13 and IL-10 by single peripheral mononuclear cells (PBMC)
      upon stimulation with islet antigens GAD65, heat shock protein 60 (Hsp60) protein
      tyrosine-phosphatase-like-antigen (pIA2) or tetanus toxoid (TT) was determined
      applying ELISPOT; beta-cell function was evaluated by glucagon stimulated C
      peptide. Multivariate regression analysis was applied. RESULTS: In general,
      number of islet antigen-reactive cells decreased over 78 weeks in both adults and
      children, whereas reactivity to TT was not reduced. In addition, there was an
      association between the quality of immune cell responses and beta-cell function.
      Overall, increased responses by IFN-gamma secreting cells were associated with
      lower beta-cell function whereas IL-5, IL-13 and IL-10 cytokine responses were
      positively associated with beta-cell function in adults and children.
      Essentially, the same results were obtained with three different models of
      regression analysis. CONCLUSIONS: The number of detectable islet-reactive immune
      cells decreases within 1-2 years after diagnosis of type 1 diabetes. Cytokine
      production by antigen-specific PBMC reactivity is related to beta-cell function
      as measured by stimulated C-peptide. Cellular immunity appears to regress soon
      after disease diagnosis and begin of insulin therapy.

PMID- 19744829
TI  - CD8+ T cell tolerance following antigen recognition on hepatocytes.
AB  - Hepatocytes, the predominant cell type in the liver, are the main cell infected
      by the hepatitis C virus (HCV) and represent important targets for immune
      therapy. Although early studies suggested that this parenchymal cell expresses
      low levels of class I MHC molecules, hepatocytes are emerging as important
      players in intrahepatic immune responses. Not only do they express high levels of
      molecules important in antigen presentation, but their expression of these
      molecules in vivo is also polarized towards the lumen of the sinusoids, thus
      maximising the efficiency of T cell activation. Electron micrographs indicate
      that interactions between T cells and hepatocytes occur in vivo via fenestrations
      in the sinusoidal endothelial layer. In this article, we will review the data
      showing that hepatocytes function as antigen presenting cells in vivo, and
      explore the fate of T cells activated by this cell type. We propose that primary
      activation of naive CD8+ T cells by hepatocytes is a critical event occurring
      during the very early stages of a HCV infection, that contributes to progression
      to viral persistence via the removal of virus-specific T cells from the T cell
      repertoire.

PMID- 19744830
TI  - Ischaemic stroke in adults and epilepsy.
AB  - Stroke is an important cause of symptomatic epilepsy especially in the elderly.
      Seizures in the setting of stroke will furthermore worsen the prognosis of
      stroke. Studies show that the frequency of seizures in stroke ranges between 2.3%
      and 14%. Typically early seizures are defined as those that occur within 14 days
      of the stroke, and later seizures those that occur after this period. A number of
      risk factors have been identified like cortical involvement, size of the infarct
      and stroke severity. Status epilepticus can be a presenting symptom of acute
      stroke and can lead to increased mortality. Early seizures are risks for
      recurrent seizures though not for the development of epilepsy but late seizures
      do carry a higher risk. There are no clear cut guidelines for the treatment of
      seizures in stroke and hence treatment needs to be initiated in the context of
      the patient. The presence of co morbid conditions and the use of other drugs also
      complicate antiepileptic therapy, and the risk of drug interactions is a
      particular hazard in elderly patients on multiple co medication. Although
      hemorrhagic and ischaemic stroke can both result in epilepsy, this review focuses
      primarily the association of epilepsy and ischaemic stroke.

PMID- 19744831
TI  - Analysis of flurothyl-induced myoclonus in inbred strains of mice.
AB  - Myoclonus is often observed in epilepsy. It is characterized by sudden
      involuntary shock-like movements of the body (myoclonic jerks, MJs). This study
      examined whether epileptic myoclonus was under genetic control. Inbred strains of
      mice were administered eight daily flurothyl exposures, a 28-day rest period, and
      a final flurothyl retest. For all trials, the latency to the first MJ (threshold)
      and the number of MJs (MJ#) were recorded. The inbred strains that we examined
      exhibited significant variability in initial myoclonic response, and myoclonus
      across the eight flurothyl exposures. C57BL/6J and DBA/2J mice displayed
      significantly different initial latencies to a MJ, MJ# preceding a generalized
      seizure (GS), and changes in MJ threshold and MJ# across the eight seizure
      trials. [C57BL/6J x DBA/2J] F1-hybrid mice showed an initial MJ threshold and
      decreases in MJ threshold over the eight trials, which were similar to C57BL/6J;
      however, F1-hybrids had an initial MJ# and trend in MJ# over the eight trials
      that were similar to DBA/2J. Decreases in MJ threshold and MJ# following multiple
      seizure trials, observed in C57BL/6J mice, were dependent on the expression of
      GSs and not on MJ occurrence. Our study is the first to document the potential
      for genetic heterogeneity of myoclonus in mice; we show that significant
      alterations in myoclonic behavior occur after GSs. These results indicate that
      multiple GSs affect MJ thresholds. An understanding of the genetics of myoclonus
      will be important for determination of the brain areas responsible for myoclonus
      as well as for identification of candidate genes.

PMID- 19744832
TI  - Neurocognitive diagnosis and cut-off scores of the Screen for Cognitive
      Impairment in Psychiatry (SCIP-S).
AB  - OBJECTIVES: To demonstrate the ability of the Screen for Cognitive Impairment in
      Psychiatry (SCIP-S) to discriminate between cognitively-impaired individuals and
      those with adequate functioning in a sample of schizophrenic and bipolar
      patients, as well as in a control group. METHODS: The SCIP-S, together with a
      full neuropsychological battery, was administered to three groups: patients with
      schizophrenia, patients diagnosed with bipolar disorder I, and controls. The
      battery scores were used to perform a standardization with respect to the control
      group and this served to determine the comparison groups (cognitively impaired
      versus unimpaired) for each of the subtests of the SCIP-S. A full analysis of
      decision validity was conducted on the basis of receiver operating characteristic
      curves (sensitivity and specificity, +LR and -LR, PPV and NPV). RESULTS: All the
      subtests yielded adequate values for sensitivity and specificity with the
      proposed cut-off points, while the total score of the SCIP (<70) was associated
      with a sensitivity of 87.9 and specificity of 80.6. CONCLUSIONS: The SCIP-S shows
      adequate decision validity as a screening tool for cognitive deficit in patients
      diagnosed with schizophrenia or bipolar disorder.

PMID- 19744833
TI  - Evaluation of the antipsychotic effect of bi-acetylated l-stepholidine (l-SPD-A),
      a novel dopamine and serotonin receptor dual ligand.
AB  - Bi-acetylated l-stepholidine (l-SPD-A), a novel derivate of l-stepholidine (l
      SPD), possesses a pharmacological profile of D(1)/5-HT(1A) agonism and D(2)
      antagonism. In the present study, we examined the potential antipsychotic effect
      of l-SPD-A in a phencyclidine (PCP)-induced rat model of schizophrenia.
      Pretreatment with l-SPD-A blocked acute PCP-induced hyperlocomotion and reversed
      prepulse inhibition (PPI) deficits. Chronic l-SPD-A administration (i.p.,
      10mg/kg/day for 14 days) improved social interaction and novel object recognition
      impairments in rats that were pretreated with PCP (i.p., 5mg/kg/day for 14 days).
      Moreover, in a conditioned avoidance response (CAR) test, l-SPD-A, with either
      i.p. or oral administration, significantly decreased active avoidance without
      affecting the escape response of rats. Importantly, compared to that of the
      parent compound l-SPD, l-SPD-A showed stronger suppression of CARs. Lastly, using
      a [(35)S]GTPgammaS binding assay, we demonstrated that l-SPD-A improved impaired
      dopamine D(1) receptor function in the prefrontal cortex (PFC) in chronic PCP
      treated rats. Taken together, these results indicate that l-SPD-A was not only
      effective against the hyperactivity, but also improved the sensorimotor gating
      deficit, social withdrawal and cognitive impairment in an animal model of
      schizophrenia. The present data suggest that l-SPD-A, a potential
      neurotransmitter stabilizer, is a promising novel candidate drug for the
      treatment of schizophrenia.

PMID- 19744834
TI  - A new insertion sequence element containing a cfiA gene in the first imipenem
      resistant Bacteroides fragilis strain isolated in Italy.

PMID- 19744835
TI  - Bacteraemia with extended-spectrum beta-lactamases-producing Escherichia coli in
      Hong Kong.

PMID- 19744836
TI  - Comparative in vitro activity of oritavancin against recent, genetically diverse,
      community-associated meticillin-resistant Staphylococcus aureus (MRSA) isolates.

PMID- 19744837
TI  - Nephrotoxicity of continuous versus intermittent infusion of vancomycin in
      outpatient parenteral antimicrobial therapy.
AB  - Intravenous (i.v.) vancomycin is increasingly used as outpatient parenteral
      antimicrobial therapy (OPAT). Despite the potential advantages of administration
      by continuous infusion (CI) compared with intermittent infusion (II), the
      relative nephrotoxicity of these two modes of delivery has not been well
      established. We compared the rate of nephrotoxicity of vancomycin given by CI and
      II. A retrospective cohort study of OPAT patients receiving i.v. vancomycin
      between January 2004 to June 2008 was performed. All patients had a normal
      baseline serum creatinine concentration. Propensity scoring analysis was used to
      adjust for risk factors of CI. The primary outcomes examined were the prevalence
      and rate of onset of nephrotoxicity. A total of 167 patients receiving vancomycin
      were identified, 112 by CI and 55 by II. The overall cumulative prevalence of
      nephrotoxicity was 15.6%. There were significant differences in baseline
      characteristics between the two groups. Matching based on propensity scores was
      undertaken, leaving 80 patients available for the analysis. Both in unadjusted
      and adjusted analyses, vancomycin CI was associated with a slower onset of
      nephrotoxicity but not a lower prevalence of nephrotoxicity. Both groups received
      a similar cumulative vancomycin dose. In adult OPAT patients with normal renal
      function, vancomycin CI was associated with a slower onset of nephrotoxicity.

PMID- 19744838
TI  - Comparative activity of oritavancin against meticillin-resistant Staphylococcus
      aureus (MRSA) bloodstream isolates from Geneva University Hospital.
AB  - In this study, we assessed by broth microdilution the in vitro activity of
      oritavancin, a semisynthetic lipoglycopeptide currently under development,
      against selected meticillin-resistant Staphylococcus aureus (MRSA) bloodstream
      isolates (n=56) from Geneva University Hospital, Switzerland, displaying a wide
      range of vancomycin minimum inhibitory concentrations (MICs) (0.25-4 microg/mL).
      The MRSA resistance phenotype was confirmed by broth microdilution (oxacillin MIC
      > or = 4 microg/mL) for all isolates; 89% and 100% of the tested isolates were
      also resistant to erythromycin and ciprofloxacin, respectively. For 53 MRSA
      isolates for which vancomycin MICs were in the susceptible range (0.5-2.0
      microg/mL), the oritavancin MICs ranged from 0.03 microg/mL to 0.5 microg/mL. For
      these 53 vancomycin-susceptible isolates, the cumulative distribution of
      oritavancin MICs was markedly different from those of vancomycin, teicoplanin,
      daptomycin and linezolid MICs, yielding an oritavancin MIC for 90% of the
      organisms (MIC(90)) (0.25 microg/mL) that was four times lower than the MIC(90)
      values (1 microg/mL) of comparators. For three MRSA isolates with a vancomycin
      intermediate phenotype (vancomycin MIC=4 microg/mL), oritavancin MICs (0.5-1.0
      microg/mL) were 2-4-fold lower than vancomycin, teicoplanin or daptomycin MICs,
      but were equivalent to linezolid MICs. Pairwise comparison for each bloodstream
      isolate showed that oritavancin was > or =4-fold more active than vancomycin,
      teicoplanin and daptomycin, against 86%, 75% and 59% of all MRSA isolates,
      respectively.

PMID- 19744839
TI  - Adsorption of cellulase Aspergillus niger on a commercial activated carbon:
      kinetics and equilibrium studies.
AB  - The adsorption kinetics of cellulase Aspergillus niger on a commercial activated
      carbon has been performed using a batch-adsorption technique. The effect of
      various experimental parameters such as initial enzyme concentration, contact
      time and temperature were investigated. The pseudo-first-order and pseudo-second
      order kinetic models were used to describe the kinetic data which shows that the
      adsorption of the enzyme followed the pseudo-second-order rate expression and the
      rate constants were evaluated. The Langmuir and Freundlich adsorption isotherm
      models were applied to describe the equilibrium isotherms, and the isotherm
      constants were determined. It was found that Langmuir model was more suitable for
      our data. The activation energy of adsorption was also evaluated for the
      adsorption of enzyme onto activated carbon. It was found 11.37 kJ mol(-1).
      Thermodynamic parameters Delta G(0), Delta H(0) and DeltaS(0) were calculated,
      indicating that this process can be spontaneous and endothermic. The adsorption
      enthalpy and entropy were found 11.12 kJ mol(-1) and 0.084 kJ mol(-1)K(-1),
      respectively. At 30 degrees C and at pH 4.8, 1g activated carbon adsorbed about
      1565 mg of cellulase, with a retention of 70% of the native enzyme activity up to
      five cycles of repeated batch enzyme reactions.

PMID- 19744840
TI  - Generation of contact-printing based poly(ethylene glycol) gradient surfaces with
      micrometer-sized steps.
AB  - A surface with a density gradient of poly(ethylene glycol) (PEG) is an attractive
      substrate for combinatorial studies of biological phenomena. In this study, the
      generation of discrete step-wise density gradients of PEG utilizing a contact
      printing approach is reported. The step-wise gradient template is achieved by
      contact-printing n-octadecyltrichlorosilane (OTS) to a glass from a hemispherical
      elastomeric stamp when the stamp is brought into contact with the substrate, and
      then step-wisely increasing the contact area as the corresponding contact
      printing time for the step decreases. A PEG-silane is then used to backfill the
      unoccupied spaces of the contact printed OTS gradient to generate the OTS-PEG
      density gradient. Various characterizations, including water contact angle
      measurement, lateral force microscopy, and X-ray photoelectron spectroscopy, are
      conducted and confirmed that the surface coverage of OTS increases (or the
      coverage of PEG decreases) with the increase of contact-printing time of OTS. The
      step-wise gradient is illustrated by adsorption of a bovine serum albumin labeled
      with fluorescein isothiocyanate and subsequent attachment of fibroblasts. The
      amounts of protein adsorption and cellular attachment increase with the decrease
      of the surface coverage of PEG.

PMID- 19744841
TI  - Fabrication of protein-anchoring surface by modification of SiO2 with liposomal
      bilayer.
AB  - SiO(2) surface was successfully modified with phospholipid bilayer for
      biocompatibility by covering the planar surface with vesicular liposomes. By
      applying heat to rupture the vesicle, they were converted into a planar form. To
      effectively decorate the bilayer with biological molecules such as a protein, BAM
      (biological anchor for membrane) was used as a linker. It is a linear assembly
      consisting of oleyl chain, polyethylene glycol, and NHS (N-hydroxysuccinimide).
      After a target protein (BSA) was conjugated with BAM by NHS replacement, the
      conjugate was effectively inserted to the phospholipid bilayer through the
      lipophilic interaction between the oleyl chain and the lipid bilayer. The entire
      process was monitored and quantitatively analyzed by QCM (quartz crystal
      microbalance). BSA-BAM conjugate showed approximately 12-fold higher binding
      efficiency to the lipid bilayer than BSA alone. From this result, we conclude
      that SiO(2) surface could be modified to a lipid bilayer surface so as to anchor
      a protein by the action of BAM.

PMID- 19744842
TI  - The treatment of bone metastasis with highly conformal radiation therapy: a brave
      new world or a costly mistake?

PMID- 19744843
TI  - Single fraction radiotherapy for bone metastases: clinically effective, time
      efficient, cost conscious and still underutilized in the United States?

PMID- 19744844
TI  - The application of ultrasound energy to increase lipid extraction throughput of
      solid matrix samples (flaxseed).
AB  - Ultrasound may reduce lipid extraction times and increase analysis throughput of
      food materials. Ground flaxseed (25mg aliquots) were extracted in quadruplicate
      in 2:1 (v:v) chloroform:methanol, 3:2 hexane:isopropanol, 1:1 diethyl:petroleum
      ether or hexane with exposure to sonication at low frequencies of 20kHz with a
      600W ultrasonic processor. Power was automatically varied to maintain constant
      amplitudes of 20%, 60% and 100% of 240microm for sonication exposures for 5, 10
      and 20min, respectively. Total lipid dry weights and quantitative and qualitative
      fatty acids were determined. Results were compared to a standard 24-h, Folch
      based, 2:1 chloroform:methanol extraction. Longer time exposures and higher
      sonication amplitudes were associated with increases in lipid recoveries. In
      particular, ultrasound-assisted extraction in 3:2 hexane:isopropanol for only
      10min resulted in lipid and fatty acid recoveries similar to the 24-h standard
      method. Comprehensive testing on a variety of sample matrices and food products
      is required, but lipid extraction by ultrasound has potential to reduce sample
      processing time.

PMID- 19744845
TI  - On the superiority of BDP/FF HFA pMDI fixed combination over the free combination
      of BDP CFC pMDI and FF DPI.

PMID- 19744846
TI  - Timothy Leary, Richard Alpert (Ram Dass) and the changing definition of
      psilocybin.
AB  - BACKGROUND: This research focuses on the events leading to the 1968 U.S. federal
      prohibition of psilocybin. It is a study of duelling moral entrepreneurs-Timothy
      Leary and Richard Alpert vs. the Harvard University Administration. The goal is
      to show how the primary active compound in an ostensibly harmless fungus (the
      psilocybin mushroom) became controversial in less than a decade. METHODS: We used
      books, newspapers, magazine articles and previously unpublished materials
      (including documents from the Harvard Archives) to analyze Leary and Alpert's
      lives and careers through the early 1970s. RESULTS: The prohibition of psilocybin
      in the U.S. was largely a product of Leary and Alpert's involvement in the
      "Harvard drug scandal" and their transformation from Harvard professors to
      countercultural icons. They tested the substance on a variety of human subjects
      and in doing so piqued the interest of Harvard undergraduates while drawing
      condemnation from other faculty and Harvard administrators. This case is
      theoretically interesting because unlike most illegal drugs, psilocybin was never
      linked to a threatening minority group, but to some of the nation's most
      privileged youth. CONCLUSION: The Harvard administrators were not really moral
      entrepreneurs but Leary and Alpert clearly were. Although they were far from
      being prohibitionists, they were self-righteous crusaders on different but
      equally holy missions for the good of young and minority Americans. Ironically,
      due to their successes the possession of psilocybin was criminalized under United
      States federal law in 1968 (Pub. L. No. 90-639, Stat. 1361 1968 and Boire, 2002).
      This case study demonstrates that crusaders can be successful in changing culture
      even when laws are passed in futile attempts to control their behaviour, just as
      Leary predicted.

PMID- 19744847
TI  - Cancer incidence in people with residential exposure to a municipal waste
      incinerator: an ecological study in Modena (Italy), 1991-2005.
AB  - We conducted a retrospective ecological study to assess cancer incidence during
      the period 1991-2005 in proximity of a municipal waste incinerator (MWI) in
      Modena (Italy). We identified three bands of increasing distance from the MWI, up
      to a radius of 5 km and used the residence as surrogate marker of the exposure.
      Residential history for Modena's population was reconstructed and residents were
      associated to the most appropriate census unit. Age-standardized incidence ratios
      (ASR) and standardized incidence ratios (SIR) were estimated for all cancers and
      selected sites. Variations in cancer incidence were investigated using space and
      space-time scan statistic. Deprivation index was taken into account as potential
      confounding factor. During the 15-year study period, 16,443 new cases of cancer
      were diagnosed among residents in Modena. The space-time clustering test
      identified three significant clusters but their shapes were not associable to the
      MWI exposition. The purely spatial analysis not showed statistically significant
      clusters. The SIR computed for all cancers and selected sites did not show any
      excess of risk in the area closest to the plant. Higher SIR for leukaemia was
      found in the second band from MWI (2-3.5 km) for females (SIR, age and DI
      adjusted: 1.35, 95%CI: 1.01-1.79) and for both sexes (SIR, age and DI adjusted:
      1.28, 95%CI: 1.03-1.57), but not a spatial trend was observed, thus excluding a
      possible link with MWI. In conclusion, bearing in mind the intrinsic limits of
      the study, the results suggest that there is no detectable increase of cancer
      risk for people living in proximity to the Modena MWI.

PMID- 19744848
TI  - Municipal solid waste effective stress analysis.
AB  - The mechanical behavior of municipal solid waste (MSW) has attracted the
      attention of many researchers in the field of geo-environmental engineering in
      recent years and several aspects of waste mechanical response under loading have
      been elucidated. However, the mechanical response of MSW materials under
      undrained conditions has not been described in detail to date. The knowledge of
      this aspect of the MSW mechanical response is very important in cases involving
      MSW with high water contents, seismic ground motion and in regions where
      landfills are built with poor operation conditions. This paper presents the
      results obtained from 26 large triaxial tests performed both in drained and
      undrained conditions. The results were analyzed taking into account the waste
      particles compressibility and the deformation anisotropy of the waste samples.
      The waste particles compressibility was used to modify the Terzaghi effective
      stress equation, using the Skempton (1961) proposition. It is shown that the use
      of the modified effective stress equation led to much more compatible shear
      strength values when comparing Consolidated-Drained (CD) and Consolidated
      Undrained (CU), results, explaining the high shear strength values obtained in CU
      triaxial tests, even when the pore pressure is almost equal to the confining
      stress.

PMID- 19744849
TI  - An integrated microfluidic system for rapid diagnosis of dengue virus infection.
AB  - This study reports an integrated microfluidic system which utilizes virus-bound
      magnetic bead complexes for rapid serological analysis of antibodies associated
      with an infection by the dengue virus. This new microfluidic system integrates
      one-way micropumps, a four-membrane-type micromixer, two-way micropumps and an on
      chip microcoil array in order to simultaneously perform the rapid detection of
      immunoglobulin G (IgG) and immunoglobulin M (IgM). An IgM/IgG titer in serum is
      used to confirm the presence of dengue virus infection. By utilizing microfluidic
      technologies and virus-bound magnetic beads, IgG and IgM in the serum samples are
      captured. This is followed by purification and isolation of these beads utilizing
      a magnetic field generated from the on-chip array of microcoils. Any interfering
      substances in the biological fluids are washed away automatically by the flow
      generated by the integrated pneumatic pumps. The fluorescence-labelled secondary
      antibodies are bound to the surface of the IgG/IgM complex attached onto the
      magnetic beads. Finally, the entire magnetic complex sandwich is transported
      automatically into a sample detection chamber. The optical signals are then
      measured and analyzed by a real-time optical detection module. The entire process
      is performed automatically on a single chip within 30min, which is only 1/8th of
      the time required for a traditional method. More importantly, the detection limit
      has been improved to 21pg, which is about 38 times better when compared to
      traditional methods. This integrated system may provide a powerful platform for
      the rapid diagnosis of dengue virus infection and other types of infectious
      diseases.

PMID- 19744850
TI  - CHOP and the endoplasmic reticulum stress response in myelinating glia.
AB  - The unfolded protein response (UPR) comprises kinase signaling and transcription
      factor activation cascades delineated over the past 20 years. Most studies
      conclude that this stress response is adaptive but, nevertheless, includes
      maladaptive programs involving CHOP expression that drives cell-autonomous
      apoptosis. Herein, we highlight several studies of UPR diseases involving
      myelinating glia of the central and peripheral nervous systems that do not
      support a primary role for CHOP in apoptosis. In oligodendrocytes, CHOP
      expression apparently protects against death whereas in Schwann cells, CHOP
      promotes demyelination in the absence of cell death. Together, these studies
      demonstrate that CHOP should be viewed more broadly as a cell-specific and
      context-specific mediator of adaptive or maladaptive responses to stress rather
      than a proapoptotic transcription factor.

PMID- 19744851
TI  - The value of surveillance mammography of the contralateral breast in patients
      with a history of breast cancer.
AB  - PURPOSE: To determine the contribution of surveillance mammography to the early
      detection of metachronous contralateral breast cancer (MCBC) and to assess its
      impact on the survival of breast cancer patients with relation to compliance.
      METHOD: Breast cancer patients (5589) were identified using files from the
      regional cancer registry of the Comprehensive Cancer Centre North Netherlands
      (CCCN Groningen, The Netherlands). The programme sensitivity and the impact on
      prognosis of follow-up mammography with relation to compliance were evaluated in
      114 patients who developed MCBC during hospital follow-up. RESULTS: The
      cumulative MCBC incidence rate at year 10 was 3.4% (95% CI: 2.8-4.0%). The
      programme sensitivity of surveillance mammography was 59.6% (95% CI: 50.6-68.7).
      In patients who complied with annual mammography, sensitivity was increased to
      70.8% (95% CI: 61.7-80.0). Patients with MCBCs detected by routine mammography
      have better survival rates than patients with MCBCs detected by other means (HR:
      3.18; 95% CI: 1.59-6.34). Though there was a trend towards improved survival in
      patients being compliant with regular clinical follow-up (HR: 1.69; 95% CI: 0.72
      3.96), this was not the case for patients being compliant with annual mammography
      (HR:1.02; 95% CI:0.50-2.09). CONCLUSION: Mammography is a valuable tool for the
      early detection of MCBC during hospital follow-up of breast cancer patients and
      is probably beneficial to survival. The utilisation of follow-up surveillance in
      breast cancer patients and its potential impact on survival deserve further
      investigation.

PMID- 19744852
TI  - Description of the national situation of cervical cancer screening in the member
      states of the European Union.
AB  - This report up-dates information on the national situation of cervical cancer
      screening in the member states of the European Union. There is yet high diversity
      in the status of cervical screening, and rapid changes expected to occur in the
      situation in many countries. It is important to underline differences in the
      health care and other components in order to allow a proper interpretation of the
      summary results published elsewhere in this Special Issue. The brief national
      descriptions along with up-dated information on the recent references are
      available from all but one member states.

PMID- 19744853
TI  - Cardiac or cardiopulmonary transplantation in childhood cancer survivors: an
      increasing need?
AB  - Childhood cancer patients now have an excellent survival rate. Anthracyclines and
      radiation have contributed to this success, unfortunately at a cost. Both
      modalities are cardiotoxic and in some cases this is fatal unless treated by
      cardiac transplantation. This population-based study investigates the requirement
      for transplantation, patient demographics and transplant outcomes. Childhood
      cancer survivors requiring a subsequent cardiac or cardiopulmonary transplant
      were identified by record linkage between the National Registry Childhood Tumours
      (NRCT) and United Kingdom Transplant registry (UKT). The clinical details were
      obtained from the treatment centres for confirmed matches. Forty-three patients
      were identified as requiring cardiac transplantation: 36 underwent
      transplantation, 4 died while waiting and 3 were removed from the list. Their
      childhood cancers included 21 haematopoietic and 22 solid tumours diagnosed at a
      median age of 3.00 years (range 0.11-13.92 years). All patients were treated with
      anthracyclines (210-750 mg/m(2)) and 15 received cardiac radiation. The median
      age at cardiac transplantation was 14.80 years (range 3.26-23.92 years) and
      actuarial survival for the 36 who underwent cardiac transplantation was 74% and
      67% at 5 and 10 years, respectively. A further three patients underwent
      heart/lung transplantation: all three died from transplant-related causes.
      Cardiac transplantation is a realistic option for cancer survivors, with survival
      rates comparable with those of other cardiac recipients. This study demonstrates
      that, over three decades, there has been an increased requirement for cardiac
      transplantation among childhood cancer survivors. Future planning for long term
      survivors needs to take this into account.

PMID- 19744854
TI  - Optimization and fed-batch production of PHB utilizing dairy waste and sea water
      as nutrient sources by Bacillus megaterium SRKP-3.
AB  - A gram positive bacterium (designated strain SRKP-3) that potentially accumulated
      polyhydroxyalkanoates (PHAs) was isolated from brackish water. From its
      morphological and physiological properties and nucleotide sequence of its 16S
      rRNA, it was suggested that strain SRKP-3 was similar to Bacillus megaterium. A
      four-factor central composite rotary design (CCRD) was employed to optimize the
      medium and to find out the interactive effects of four variables, viz.
      concentrations of dairy waste, rice bran, sea water and pH on PHB production.
      Using response surface methodology (RSM), a second-order polynomial equation was
      obtained by multiple regression analysis and a yield of 6.37 g/L of PHB dry
      weight was achieved from the optimized medium at pH 9. The same medium was
      utilized for fermentor studies by fed-batch culture. The dairy waste is fed at
      three different time intervals at 0 th, 12th and 24th hour to keep the carbon
      source as excess and PHB production was checked for every 3h. Maximum production
      of PHB (11.32 g/L) occurred at 36th hour. Dissolved oxygen was found to be major
      limiting nutrient that affected the PHB synthesis.

PMID- 19744855
TI  - Cell regulation: determined to signal discrete cooperation.
AB  - Do kinases cascade? How well is cell regulation understood? What are the best
      ways to model regulatory systems? Attempts to answer such questions can have
      bearings on the way in which research is conducted. Fortunately there are
      recurring themes in regulatory processes from many different cellular contexts,
      which might provide useful guidance. Three principles seem to be almost
      universal: regulatory interactions are cooperative; regulatory decisions are made
      by large dynamic protein complexes; and regulation is intricately networked. A
      fourth principle, although not universal, is remarkably common: regulatory
      proteins are actively placed where they are needed. Here, I argue that the true
      nature of cell signalling and our perceptions of it are in a state of discord.
      This raises the question: Are our misconceptions detrimental to progress in
      biomedical science?

PMID- 19744856
TI  - Mycobacterium fortuitum infection after anterior cruciate ligament reconstruction
      using a polylactic acid bioabsorbable screw: Case report.
AB  - We report a case of pretibial sinus and abscess after anterior cruciate ligament
      reconstruction using a polylactic acid tricalcium phosphate bioabsorbable screw
      for tibial fixation. Mycobacterium fortuitum was identified as the pathogen after
      specific mycobacterial cultures were obtained from operative specimens. M.
      fortuitum is a known but rare cause of periprosthetic infection. Diagnosis is
      often delayed as routine microbiological cultures do not utilise specific culture
      requirements for mycobacterial growth. There have been several reports in the
      literature of sterile abscesses associated with bioabsorbable screws. To our
      knowledge, this is the first case report of a non-tuberculous mycobacterial
      infection associated with a bioabsorbable implant. This case illustrates that
      post-operative Mycobacterium infection can occur as a complication of ACL
      reconstruction with bioabsorbable screw fixation and should be considered in the
      differential diagnosis of post-operative periprosthetic infection.

PMID- 19744857
TI  - Effect of tendon tensioning: an in vitro study in porcine extensor tendons.
AB  - Graft tensioning is a controversial issue in anterior cruciate ligament
      reconstruction (ACLR) that has not achieved consensus between peers. The purpose
      of this study is to determine if after tensioning tendon length and resistance to
      maximal load changes. We performed an in vitro study with 50 porcine extensors
      tendons. The first group (P=25) was tensioned with 80 N (19.97 lb) for 10 min,
      using an ACL graft preparation board. The second group (C=25) was used as control
      and was not tensioned. The average initial (groups P and C) and post tensioning
      tendon length (group C) were measured; the average initial and post tensioning
      tendon diameter were measured as well. All samples were fixated in a tube-clamp
      system connected to a tension sensor. The samples were stressed with continuous
      and progressive tension until ultimate failure at maximum load (UFML) occurs. The
      initial mean length was: P before tensioning=13.4 mm+/-1.4 mm (range 10.5-16.5);
      P after tensioning=13.8 mm+/-1.4 mm (range 11.5-16.5); C=13 mm+/-1.35 mm
      (p=0.005). The mean diameter was: P=5.6 mm (4.5-6); C=5.5 mm (range 4.5-6)
      (p>0.05). The UFML was: P=189.7 N (114-336); C=229.9 N (143-365) (p=0.029).
      Tendon tensioning with 80 N for 10 min produced 3% average elongation. These
      could be beneficial in ACLR since tendon tensioning decreases elongation of the
      graft after fixation. Regardless, tendon tensioning is not innocuous since it
      diminishes their resistance when continuously stressed until complete failure
      occurs.

PMID- 19744858
TI  - Synthesis and in vitro activities of new anticancer duplex drugs linking 2'-deoxy
      5-fluorouridine (5-FdU) with 3'-C-ethynylcytidine (ECyd) via a phosphodiester
      bonding.
AB  - Two isomeric cytostatic duplex drugs 2'-deoxy-5-fluorouridylyl-(3'-->5')-3'-C
      ethynylcytidine [5-FdU(3'-->5')ECyd] and 2'-deoxy-5-fluorouridylyl-(5'-->5')-3'-C
      ethynylcytidine [5-FdU(5'-->5')ECyd] were designed and synthesized at gram scale
      according to the hydrogenphosphonate method in an overall yield of about 40%. The
      in vitro evaluation of the anticancer effects indicated highly varying
      sensibilities of the panel of 60 tested tumor cell lines against the duplex
      drugs. 5-FdU(3'-->5')ECyd had a 50% growth inhibition (IC(50) < or = 10(-8) M) in
      44/58 cell lines. However, only 25/53 of those cell lines showed corresponding
      IC(50) values when the isomeric 5-FdU(5'-->5')ECyd was tested. Total growth
      inhibition was achieved using micromolar concentrations of the duplex drugs. The
      5-FdU residue of the duplex drug can cause very different effects like additive,
      synergistic, antagonistic as well as sequence-depending activities, which
      drastically changed efficiency as well as specificity of the anticancer
      activities of the duplex drugs, in comparison to those of the monomeric drugs.

PMID- 19744859
TI  - Dibenzazecine scaffold rebuilding--is the flexibility always essential for high
      dopamine receptor affinities?
AB  - The moderately flexible 7-methyl-5,6,7,8,9,14-hexahydrodibenz[d,g]azecines are
      known to be potent dopamine receptor antagonists, whereas the corresponding rigid
      dibenzo[d,g]quinolizines are inactive. We built the scaffolds of dibenzo[c,g],
      [c,f] and [d,f]azecines and together with their ring closed, more rigid
      precursors, evaluated the affinities for the human D(1)-D(5) receptors
      (radioligand binding) as well as the functionalities (calcium assay) and thus
      investigated the influence of annelation and conformative flexibility of these
      compounds on their affinity for human cloned dopamine receptors.

PMID- 19744860
TI  - Synthesis and biological evaluation of novel phthalazinone derivatives as
      topically active phosphodiesterase 4 inhibitors.
AB  - Inhibitors of phosphodiesterase 4 (PDE4) are an important class of anti
      inflammatory drug that act by inhibiting the production of proinflammatory
      cytokines, including tumor necrosis factor-alpha (TNF-alpha). We have synthesized
      and evaluated a series of 2-substituted phthalazinone derivatives as PDE4
      inhibitors. Structure-activity relationship studies led to the identification of
      benzylamine-substituted phthalazinones as potent PDE4 inhibitors that also
      suppressed TNF-alpha production by whole rat blood cells. The most potent of
      these, when topically administered, were effective in a mouse model of
      dermatitis.

PMID- 19744861
TI  - A new therapeutic approach in Parkinson's disease: some novel quinazoline
      derivatives as dual selective phosphodiesterase 1 inhibitors and anti
      inflammatory agents.
AB  - The increasing life expectancy in our population makes Parkinson's disease (PD) a
      growing public health problem. There is a great need to find a way to prevent and
      delay the disease. It was shown that selective phosphodiesterase 1 (PDE1)
      inhibitors and anti-inflammatory agents might be effective in treating PD.
      Therefore, a novel 1,2,9,11-tetrasubstituted-7H-thieno[2',3':4,5]pyrimido[6,1-b]
      quinazolin-7-one (1-15) and 1,3,10,12-tetrasubstituted-8H
      pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one (16-36) derivatives were
      synthesized by reported method and investigated for their ability to inhibit
      PDE1. Most of the synthesized compounds have shown good activity against PDE1 and
      were less effective than 3-isobutyl-1-methylxanthine. All the compounds were also
      tested for their in vitro anti-inflammatory activity by carrageenan-induced
      oedema in rats. In addition, ulcerogenic activity was determined. The combined
      anti-inflammatory data from in vitro animal model showed that compounds, 9,11
      dibromo-1-(2-furyl)-3-(4-tolyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8
      one 23, 9,11-dibromo-1-(4-methoxy-phenyl)-3-phenyl-8H
      pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one 24, 9,11-dibromo-1-(4-chloro
      phenyl)-3-(4-tolyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one 29 and 9
      bromo-1-(4-chloro-phenyl)-3-(4-tolyl)-8H-pyrido[2',3':4,5]pyrimido[6,1
      b]quinazolin-8-one 36 exhibited even more potent anti-inflammatory activity and
      low gastric ulceration incidence compare to reference standard Indomethacin.
      Since compound 23, 24, 29 and 36 exhibits both anti-inflammatory activity and
      PDE1 inhibition, it needs further detailed studies.

PMID- 19744862
TI  - X-ray fluorescence with synchrotron radiation to elemental analysis of lead and
      calcium content of primary teeth.
AB  - Primary teeth were analyzed by micro-SRXRF. The aim of this study was to
      determine the elemental distribution of lead and calcium in different regions of
      primary incisor of children living in a notoriously contaminated area (Santo
      Amaro da Purificacao, Bahia State, Brazil). The measurements were performed in
      standard geometry of 45 degrees incidence, exciting with a white beam and using a
      conventional system collimation (orthogonal slits) in the XRF beamline at the
      Synchrotron Light National Laboratory (Campinas, Brazil).

PMID- 19744863
TI  - Nucleophile addition of reduced glutathione on 2-methyl-2-nitroso compound: a
      combined electron paramagnetic resonance spectroscopy and electrospray tandem
      mass spectrometry study.
AB  - Mass spectrometry (MS) was used in conjunction with electron paramagnetic
      resonance (EPR) to characterize products arising from reactions between reduced
      glutathione (GSH) and 2-methyl 2-nitroso propane (MNP) in an oxidative medium, to
      evaluate the reactivity of this tripeptide as a nucleophile toward a nitroso
      compound. Depending on the experimental conditions, different radical species
      could be detected by EPR, which allowed some structural assumptions. These
      samples were then submitted to electrospray ionization, in both positive and
      negative ion modes, for structural elucidation in tandem mass spectrometry.
      Although the primary nitroxide products could not be detected in MS, structurally
      related compounds such as hydroxylamine and O-methyl hydroxylamine could be fully
      characterized. In the absence of light, a S-adduct was formed via a Forrester
      Hepburn reaction, that is, a nucleophile addition of MNP onto the thiol function
      in reduced glutathione to yield a hydroxylamine intermediate, further oxidized
      into nitroxide. In contrast, irradiating the reaction medium with visible light
      could allow an inverted spin trapping reaction to take place, involving the
      oxidation of both MNP and GSH before the nucleophilic addition of the sulfenic
      acid function onto the nitrogen of MNP, yielding a so-called O-adduct. It was
      also found that dilution of the reaction medium with methanol for the purpose of
      electrospray ionization could allow nitroxides to be indirectly observed either
      as hydroxylamine or O-methyl hydroxylamine species.

PMID- 19744864
TI  - First Ron Hites Award goes to Alison E. Ashcroft, Sheena Radford, and Coauthors.

PMID- 19744865
TI  - Electrospray ionization quadrupole ion-mobility time-of-flight mass spectrometry
      as a tool to distinguish the lot-to-lot heterogeneity in N-glycosylation profile
      of the therapeutic monoclonal antibody trastuzumab.
AB  - Monoclonal antibodies are typically glycosylated at asparagine residues in the Fc
      domain, and glycosylation heterogeneity at the Fc sites is well known. This paper
      presents a method for rapid analysis of glycosylation profile of the therapeutic
      monoclonal antibody trastuzumab from different production batches using
      electrospray quadrupole ion-mobility time-of-flight mass spectrometry (ESI-Q-IM
      TOF). The global glycosylation profile for each production batch was obtained by
      a fast LC-MS analysis, and comparisons of the glycoprofiles of trastuzumab from
      different lots were made based on the deconvoluted intact mass spectra.
      Furthermore, the heterogeneity at each glycosylation site was characterized at
      the reduced antibody level and at the isolated glycopeptide level. The
      glycosylation site and glycan structures were confirmed by performing a time
      aligned-parallel fragmentation approach using the unique dual-collision cell
      design of the instrument and the incorporated ion-mobility separation function.
      Four different production batches of trastuzumab were analyzed and compared in
      terms of global glycosylation profiles as well as the heterogeneity at each
      glycosylation site. The results show that each batch of trastuzumab shares the
      same types of glycoforms but relative abundance of each glycoforms is varied.

PMID- 19744866
TI  - Reliability and interpretation of single leg stance and maximum voluntary
      isometric contraction methods of electromyography normalization.
AB  - Normalization of electromyographic (EMG) amplitudes is necessary in the study of
      human motion. However, there is a lack of agreement on the most reliable and
      appropriate normalization method. This study evaluated the reliability of single
      leg stance (SLS) and maximal voluntary isometric contraction (MVIC) normalization
      methods and the relationship between these measures for the gluteus maximus
      (GMax), gluteus medius (GMed), rectus femoris (RF), vastus lateralis (VL), hip
      adductor group (ADD), and biceps femoris (BF). Surface EMG was recorded in 20
      subjects during three 5s trials of SLS and MVIC. SLS and MVIC methods both
      demonstrated good-to-excellent reliability in all muscles (ICCs>0.80).
      Intrasubject coefficients of variation were lower for the MVIC method (9-36%)
      than for the SLS method (20-59%). EMG amplitudes during MVIC and SLS were
      significantly correlated for all muscles (Pearson r's=0.604-0.905, p<0.005)
      except GMax (r=0.250, p=0.288). Use of SLS normalization for the RF, VL, and BF
      is not recommended due to a lack of measurement precision. However, this method
      is justified in the GMax, GMed, and ADD and may provide a better representation
      of coordinated muscle function during a functional task.

PMID- 19744867
TI  - Results of surgical treatment compared with ultrasound-guided foam sclerotherapy
      in patients with varicose veins: a prospective randomised study.
AB  - OBJECTIVE: This study aims to compare venous clinical severity scores in patients
      with healed venous ulcers due to varicose veins of the lower limbs (the clinical,
      etiologic, anatomic, and pathophysiologic data (CEAP) classification: C(5)
      EpAsPr) treated by saphenous stripping and phlebectomy or by ultrasound-guided
      foam sclerotherapy. METHOD: Sixty patients were included: 29 underwent saphenous
      stripping and phlebectomy for varices in saphenous tributaries and 27 were
      treated by ultrasound-guided foam sclerotherapy; four cases were lost to follow
      up. The main outcome measure was venous clinical severity scores (pain, oedema,
      inflammation, hyperpigmentation and lipodermatosclerosis). An ultrasound
      examination was carried out prior to treatment and 30, 60 and 180 days after the
      procedure to assess the relative efficacy of the methods in obliterating the
      saphenous trunk. RESULTS: The mean venous clinical severity scores measured
      before and after 180 days were as follows: Surgery group - pain: before 1.97
      standard deviation (SD) 0.19, 180 days 0.72 SD 0.53; oedema: before 1.66 SD 0.48,
      180 days 0.55 SD 0.63; inflammation: before 1.55 SD 0.63, 180 days 0.72 SD 0.45.
      Foam sclerotherapy group - pain: before 1.81 SD 0.40, 180 days 0.56 SD 0.51;
      oedema: before 1.70 SD 0.47, 180 days 0.48 SD 0.64; inflammation: before 1.67 SD
      0.68, after 0.89 SD 0.32. All scores showed statistically significant reductions
      in both patient groups. The saphenous vein had been obliterated, 180 days after
      treatment, in 78% of the surgery group, compared with 90% in the foam
      sclerotherapy group. CONCLUSIONS: Ultrasound-guided foam sclerotherapy is a safe
      and effective option for patients with chronic venous disorders.

PMID- 19744868
TI  - Carotid endarterectomy improves cerebrovascular reserve capacity preferentially
      in patients with preoperative impairment as indicated by asymmetric BOLD response
      to hypercapnia.
AB  - PURPOSE: In patients with symptomatic carotid artery disease the predominant
      mechanism causing ischaemic injury is considered to be thromboembolic, however
      compromise of cerebral haemodynamics is considered to be a significant factor.
      Removal of the embolic source is accepted as the major benefit from carotid
      endarterectomy (CEA), however improvement in cerebral haemodynamics may be
      another beneficial outcome as suggested by transcranial doppler (TCD). Blood
      oxygen level-dependent (BOLD) hypercapnia functional magnetic resonance imaging
      (fMRI) can be used to map the cerebrovascular reserve (CVR). The aim of this
      study was to assess the effects of carotid surgery on cerebral haemodynamics in
      patients with carotid artery disease using a hypercapnia BOLD fMRI and assessment
      of hemispheric asymmetry. MATERIALS AND METHODS: Seventeen patients with
      symptomatic internal carotid artery stenosis were scanned using a clinical 1.5T
      MR scanner. Scanning was done immediately prior to and between 4 and 8 weeks
      after CEA. 10% carbon dioxide was administered to achieve transient episodes of
      hypercapnia. The data was analyzed using FMRIB Software Library (FSL) software to
      derive percentage signal change (PSC) for the grey matter of the middle cerebral
      artery (MCA-GM) territory for both hemispheres. MCA-GM PSC was furthermore
      normalized to the contralateral hemisphere to derive an Hemispheric Asymmetry
      Index (hAI) for all patients pre- and postoperatively. RESULTS: Ipsilateral GM
      CVR improved significantly following CEA (2.47% preoperatively vs. 2.73%
      postoperatively, p=0.038). There was no change in CVR in the contralateral grey
      and white matter MCA territories (p=0.27, p=0.1). Also, the hAI was significantly
      more shifted to the ipsilateral hemisphere after CEA (preoperative hAI -0.56, vs.
      -3.90 postoperatively, p=0.02). Patients with an impaired hAI preoperatively were
      found to show the greatest improvement in PSC and hAI following CEA (p=0.007).
      CONCLUSIONS: CEA resulted in improved CVR in patients with carotid artery disease
      as shown by the absolute and hemispheric asymmetry of BOLD response to
      hypercapnia.. These findings show that benefits from recanalisation may go beyond
      removal of the embolic source, by improving the cerebrovascular reserve.
      Moreover, hypercapnia BOLD fMRI may be a useful clinical tool in predicting this
      therapeutic potential in patients with severe carotid artery disease.

PMID- 19744869
TI  - Retinal degeneration in cats: a tale of two means of motion.

PMID- 19744870
TI  - FID detection of EPR and ENDOR spectra at high microwave frequencies.
AB  - High-frequency pulsed EPR spectroscopy allows FID detection of EPR spectra owing
      to the short dead time that can be achieved. This FID detection is particularly
      attractive for EPR and ENDOR spectroscopy of paramagnetic species that exhibit
      inhomogeneously broadened EPR lines and short dephasing times. Experiments are
      reported for the metalloprotein azurin at 275 GHz.

PMID- 19744871
TI  - Evidence for the Thr79Met polymorphism of the ileal fatty acid binding protein
      (FABP6) to be associated with type 2 diabetes in obese individuals.
AB  - The ileal fatty acid binding protein (FABP6) is known to be involved in
      enterohepatic bile acid metabolism. We have previously found a significant
      association between the rare allele of the FABP6 Thr79Met polymorphism and lower
      type 2 diabetes risk in a small case-control study (192 cases and 384 controls)
      embedded in the large EPIC-Potsdam cohort. A priori functional implication of the
      amino acid change was gained from in-silico analysis. In this study, we analysed
      an independent nested case-cohort including 543 incident type 2 diabetes cases
      from the EPIC-Potsdam cohort and a case-control study including 939 type 2
      diabetes cases from KORA to confirm the association with type 2 diabetes and
      performed association analyses with quantitative disease-related measures in 2112
      non-diabetic individuals. Homozygosity for the Met-allele was associated with
      lower risk of type 2 diabetes (EPIC-Potsdam: 0.70, P=0.04; KORA: 0.79, P=0.06) if
      adjusted for age, sex, body mass index (BMI), and waist circumference. The
      homozygous rare variant showed a significant interaction (P=0.006) with BMI.
      Relative risks in different categories (BMI <25, 25-30, and >30 kg/m(2)) showed
      an association exclusively in obese (BMI >30 kg/m(2)) individuals (combined risk
      ratio: 0.62, 95% CI 0.45-0.86). In non-diabetic individuals from the general
      adult population, no significant associations were observed with plasma total
      cholesterol, LDL-, and HDL-cholesterol, triglyceride, insulin and glucose
      concentration. In summary, we found evidence that the-putative functional
      Thr79Met substitution of FABP6 confers a protective effect on type 2 diabetes in
      obese individuals.

PMID- 19744872
TI  - Sonographic pleural fluid volume estimation in cats.
AB  - The aims of this study were to evaluate whether a recently published study used
      to objectively monitor pleural fluid volumes in dogs could be successfully
      employed in cats and secondly to assess its accuracy. Eleven feline cadavers were
      selected. Using the trans-sternal view employed in dogs, linear measurements from
      the pleural surface of the midline of the sternebra at the centre of the heart to
      the furthest ventro-lateral point of both right and left lung edges were
      recorded. Isotonic saline was injected using ultrasound guidance into both right
      and left pleural spaces and the measurements were repeated using standard
      increments until 400 ml total volume was reached. The mean measurement increased
      in a linear relationship with the cube root of fluid volume for all cats
      individually. An equation was produced to predict the volume of fluid from the
      mean linear measurement for all cats combined: Volume=[
      3.75+2.41(mean)](3)(P<0.001) but variability in the slope of the curve for
      individual cats limited the accuracy of the combined equation. Equations were
      derived to predict the constant and slope of the curve for individual cats using
      the thoracic measurements made, but the residual diagnostic graphs demonstrated
      considerable variability. As in dogs, good correlation was found between the
      ultrasonographic measurement and fluid volume within individual cats. An accurate
      equation to predict absolute pleural fluid volume was not identified. Further
      analysis with reference to thoracic measurements did not increase accuracy. In
      conclusion, this study does provide a method of estimating absolute pleural fluid
      volume in cats, which may be clinical useful for pleural fluid volume monitoring
      but this is yet to be validated in live cats.

PMID- 19744873
TI  - Mesh morphing for finite element analysis of implant positioning in cementless
      total hip replacements.
AB  - Finite element (FE) analysis of the effect of implant positioning on the
      performance of cementless total hip replacements (THRs) requires the generation
      of multiple meshes to account for positioning variability. This process can be
      labour intensive and time consuming as CAD operations are needed each time a
      specific orientation is to be analysed. In the present work, a mesh morphing
      technique is developed to automate the model generation process. The volume mesh
      of a baseline femur with the implant in a nominal position is deformed as the
      prosthesis location is varied. A virtual deformation field, obtained by solving a
      linear elasticity problem with appropriate boundary conditions, is applied. The
      effectiveness of the technique is evaluated using two metrics: the percentages of
      morphed elements exceeding an aspect ratio of 20 and an angle of 165 degrees
      between the adjacent edges of each tetrahedron. Results show that for 100
      different implant positions, the first and second metrics never exceed 3% and
      3.5%, respectively. To further validate the proposed technique, FE contact
      analyses are conducted using three selected morphed models to predict the strain
      distribution in the bone and the implant micromotion under joint and muscle
      loading. The entire bone strain distribution is well captured and both
      percentages of bone volume with strain exceeding 0.7% and bone average strains
      are accurately computed. The results generated from the morphed mesh models
      correlate well with those for models generated from scratch, increasing
      confidence in the methodology. This morphing technique forms an accurate and
      efficient basis for FE based implant orientation and stability analysis of
      cementless hip replacements.

PMID- 19744874
TI  - Beyond the male-migrant: South Africa's long history of health geography and the
      contemporary AIDS pandemic.
AB  - This article begins by noting the contribution that past South African writings
      on health can make to the field of health geography-especially writings on male
      migration and syphilis from the 1940s that conceptualized space as relational.
      However, the second part of the article notes that the rapid rise of AIDS in the
      post-apartheid period influenced the problematic projecting forward of the male
      migrancy model. Ethnographic and secondary data show how AIDS is embedded in
      under-researched social and spatial structures after apartheid. In tracing these
      processes the article combines anthropology, geography, and political economy to
      chart an interdisciplinary analysis of the uneven geographies of health.

PMID- 19744875
TI  - Where do young Irish women want Chlamydia-screening services to be set up? A
      qualitative study employing Goffman's impression management framework.
AB  - We conducted interviews with 35 young women recruited from eight community
      healthcare rural and urban settings across two regions of Ireland. The aim of the
      study was to explore where these women thought Chlamydia-screening services
      should be located. Respondents wanted screening services to be located in
      settings where they would not be witnessed either asking for, or being asked to
      take, Chlamydia tests. Respondents were worried that their identities would
      become stigmatized if others were to find out that they had accepted screening.
      Findings are interpreted through Goffman's stigma and impression management
      framework. We conclude with public health recommendations.

PMID- 19744876
TI  - Thoracic outlet syndrome part 1: clinical manifestations, differentiation and
      treatment pathways.
AB  - Thoracic outlet syndrome (TOS) is a challenging condition to diagnose correctly
      and manage appropriately. This is the result of a number of factors including the
      multifaceted contribution to the syndrome, the limitations of current clinical
      diagnostic tests, the insufficient recognition of the sub-types of TOS and the
      dearth of research into the optimal treatment approach. This masterclass
      identifies the subtypes of TOS, highlights the possible factors that contribute
      to the condition and outlines the clinical examination required to diagnose the
      presence of TOS.

PMID- 19744878
TI  - System-level analysis of Salmonella metabolism during infection.
AB  - Infectious diseases represent a major threat to human health. To develop urgently
      needed new control strategies, a transition from research focusing on individual
      factors to a more integrated system-level analysis might be needed. Such an
      approach faces great challenges and might require development of new concepts in
      large-scale data analysis. Here, I discuss for the well-characterized model
      pathogen Salmonella, how extensively studied metabolism can be used as a training
      field for infection biology at the systems level. Extensive experimental data can
      be analyzed in context using metabolic network visualization tools and in silico
      modeling based on genome-scale metabolic reconstructions. Suitable approaches to
      obtain still missing comprehensive quantitative data on Salmonella nutrition in
      infected host tissues are described. Such an integrated investigation of
      Salmonella metabolism during infection will enable an unprecedented large-scale
      understanding of pathogen in vivo activities, help to evaluate concepts and
      strategies for system-level analysis of host/pathogen interactions in general,
      and provide a basis for rational development of novel antimicrobials and
      efficacious live vaccines.

PMID- 19744877
TI  - Lipidomics: a mass spectrometry based systems level analysis of cellular lipids.
AB  - Lipidomics is a logical outcome of the history and traditions of lipid
      biochemistry and advances in mass spectrometry are at the heart of a renaissance
      in understanding the roles of lipids in cellular functions. Our desire to
      understand the complexity of lipids in biology has led to new techniques that
      allow us to identify over 1000 phospholipids in mammalian cell types and tissues.
      Improvements in chromatographic separation and mass spectrometry have positioned
      us to determine not only the lipid composition (i.e. parts list) of cells and
      tissues, but also address questions regarding lipid substrates and products that
      previously overwhelmed traditional analytical technologies. In the decade since
      lipidomics was conceived much of the efforts have been on new methodologies,
      development of computer programs to decipher the gigabytes of raw data, and
      struggling with the highly variable nature of biological systems where absolute
      quantities of a given metabolite may be less important than its relative change
      in concentration. It is clear that the technology is now sufficiently developed
      to address fundamental questions about the roles of lipids in cellular signaling
      and metabolic pathways.

PMID- 19744879
TI  - Novel biological insights through metabolomics and 13C-flux analysis.
AB  - Metabolomics and (13)C-flux analysis have become instrumental for analyzing
      cellular metabolism and its regulation. Driven primarily by technical advances in
      mass spectrometry-based analytics, they provide unmatched readouts on metabolic
      state and activity. Functional genomics leverages metabolomics for the discovery
      of novel enzymes and unexpected secondary activities of annotated enzymes. (13)C
      flux analyses are frequently used for empirical elucidation of pathways in poorly
      characterized species and for network-wide analysis of mechanisms that realize
      energy and redox balancing. Integration of metabolomics, (13)C-flux analysis and
      other data enable the condition-dependent characterization of regulatory circuits
      that ultimately govern the metabolic phenotype.

PMID- 19744880
TI  - Green synthesis of gold nanoparticles using Cinnamomum zeylanicum leaf broth.
AB  - Development of biologically inspired experimental processes for the synthesis of
      nanoparticles is an important branch of nanotechnology. The synthesis of gold
      nanoparticles using Cinnamomum zeylanicum leaf broth as the reducing agent is
      reported. The morphology of the particles formed consists of a mixture of gold
      nanoprisms and spheres with fcc (111) structure of gold. At lower concentrations
      of the extract, formation of prism shaped Au particles dominates, while at higher
      concentrations almost spherical particles alone are observed. Good crystallinity
      of the nanoparticles with fcc phase is evident from XRD patterns, clear lattice
      fringes in the high resolution TEM image and bright circular rings in the SAED
      pattern. Au nanoparticles grown are observed to be photoluminescent and the
      intensity of photoemission is found to increase with increase in leaf broth
      concentration. The ability to modulate the shape of nanoparticles as observed in
      this study for gold nanoparticles opens up the exciting possibility of developing
      further synthetic routes employing ecofriendly sources.

PMID- 19744881
TI  - Solvatochromism and temperature effects on the electronic absorption spectra of
      some azo dyes.
AB  - The UV-visible electronic spectra of some azo dyes have been studied. The
      different bands observed in the electronic spectra of the compounds in various
      organic solvents have been assigned to the proper electronic transitions. The
      solvatochromic behaviour of these compounds was investigated by studying their
      visible spectra in several pure and mixed organic solvents. The longer wavelength
      band displayed by para-nitro azo dyes is assigned to an intermolecular charge
      transfer transition. The solvated H-bonding complexes formed between N,N
      dimethylformamide and the para-nitro azo dyes were investigated. DeltaG and
      formation constant, the values of K(f) of the molecular complexes formed in
      solution have been determined. The effects of increase of temperature and
      concentration dependent spectroscopic changes on the longer wavelength visible
      band of para-nitro azo dyes were also investigated.

PMID- 19744882
TI  - Tuning the optical properties of ZnTPP using carbonyl ring fusion.
AB  - Zinc meso-tetraphenylporphyrin (ZnTPP) was modified in such a way to allow the
      effect of an asymmetric structural distortion on its optical properties to be
      investigated. This involved the fusion of a phenyl group to an adjacent pyrrole
      ring via a carbonyl bridge. With the aid of Density Functional Theory (DFT) and
      time-dependent DFT (TD-DFT) calculations it was found that the asymmetric
      distortion away from planarity induced by the carbonyl fusion resulted in a loss
      of degeneracy in the two lowest unoccupied molecular orbitals (LUMOs). The effect
      was a red shift of the electronic absorbance bands, an increased Q:B ratio from
      0.046 in ZnTPP to 0.096 in the fused derivative, and the appearance of additional
      UV-vis peaks. This study therefore suggests that structural distortions, as well
      as electronic substituents may be used to alter absorbance spectra, a technique
      which is of interest in the design of light-harvesting dyes.

PMID- 19744883
TI  - Studies on the full vibrational energies and dissociation energies of some
      heteronuclear diatomic molecules.
AB  - A parameter-free analytical formula for dissociation energies of diatomic
      molecules is proposed by Fan and Sun (2009) [20] based on LeRoy and Bernstein's
      vibrational energy expression near dissociation limit. Using three highest
      vibrational energies which may be generated by the algebraic method (AM)
      presented in our previous study and by some other physical methods, the new
      formula is applied to study the molecular dissociation energies of 10 electronic
      states of KH, (7)LiD, (7)LiH, (6)LiH, NaK, NaLI and NaRb heteronuclear diatomic
      molecules which have regular (Morse-like) potentials in this work. The results
      show that the AM energies E(upsilon)(AM) and dissociation energies D(e)(AM) have
      excellent agreement with experimental values.

PMID- 19744884
TI  - Radiofrequency ablation for atrial fibrillation in rheumatic valvular disease.
AB  - BACKGROUND: We have reviewed the results of radiofrequency ablation (RFA) in
      patients with rheumatic valve disease. METHODS: Sixty-seven patients underwent
      operation for rheumatic valvular disease and RFA concomitantly with the planned
      procedure. Twenty-two (32.8%) were male and 45 (67.2%) female. The mean duration
      of atrial fibrillation (AF) was 47.4+/-30.4 months (12-192). Logistic regression
      test was used to perform a risk factor analysis. RESULTS: Two patients died
      postoperatively (3.0%) and 3 died in the follow-up period (4.5%). One patient
      (1.5%) required permanent pacemaker. During the hospitalisation, 24 patients
      (35.8%) had AF but 6 of them returned to the normal sinus rhythm by the time of
      discharge. Forty-nine patients (73.1%) were discharged with normal sinus rhythm.
      The mean duration of follow-up was 15.1+/-15.2 months (0-59). Six patients (9.0%)
      had recurrent AF during the follow-up period. For early AF recurrence male sex
      was a significant risk factor (p=0.028) with an odds ratio 8627 (CI 95% 1261
      59,006). CONCLUSIONS: The low sinus rhythm rate at discharge and high rates of
      recurrence may be attributed to the disease nature. Males are at increased risk
      of early AF recurrence but no significant risk factors for late recurrence have
      been found.

PMID- 19744885
TI  - Survival of the fittest: allergology or parasitology?
AB  - Allergologists have long recognized that only a small fraction of the
      environmental and food proteins that we are exposed to give rise to IgE
      responses. This has raised the intriguing and important question: What makes an
      allergen an allergen? Many protein allergens have close homologs in metazoan
      parasites, and as helminth genome information grows, it appears increasingly
      clear that not only are the immune mechanisms of allergy and anti-helminth
      immunity closely related, but so are the helminth and allergen proteins that
      induce them. This suggests that at least part of the secret of what allows some
      proteins to be allergens may actually lie in the long co-evolutionary
      relationship between worms and their vertebrate (and latterly human) hosts.

PMID- 19744886
TI  - The role of specific Toxoplasma gondii molecules in manipulation of innate
      immunity.
AB  - Infection with the parasite Toxoplasma gondii stimulates an innate immune
      response in the host. T. gondii also induces alterations in infected monocytes
      and dendritic cells that probably contribute to its ability to disseminate and
      ultimately to establish persistent infection. Recent progress has linked specific
      parasite molecules to immune stimulation or the ability of the parasite to
      subvert intracellular signaling pathways in infected cells to evade immunity.

PMID- 19744887
TI  - Predicting changing malaria risk after expanded insecticide-treated net coverage
      in Africa.
AB  - The Roll Back Malaria (RBM) partnership has established goals for protecting
      vulnerable populations with locally appropriate vector control. In many places,
      these goals will be achieved by the mass distribution of insecticide treated
      bednets (ITNs). Mathematical models can forecast an ITN-driven realignment of
      malaria endemicity, defined by the Plasmodium falciparum parasite rate (PfPR) in
      children, to predict PfPR endpoints and appropriate program timelines for this
      change in Africa. The relative ease of measuring PfPR and its widespread use make
      it particularly suitable for monitoring and evaluation. This theory provides a
      method for context-dependent evaluation of ITN programs and a basis for setting
      rational ITN coverage targets over the next decade.

PMID- 19744888
TI  - Problem of bacterial contamination in platelet concentrates.
AB  - Bacterial contamination of blood is being recognized more frequently now and is
      one of the serious complications of transfusion. Use of integrally attached
      collection systems and strict standards for skin preparation, collection and
      storage of blood and components have reduced but not eliminated the risk of
      bacterial contamination. As bacteraemia may be part of acute or sub acute
      infections, strict donor selection is warranted. The longer the storage time, the
      greater is the number of organisms and amount of endotoxin present in the unit
      and associated with transfusion reactions. Importance of haemovigilance system
      and awareness among clinicians on the potential complications will go a long way
      in reducing patient morbidity. New approaches for detection of bacterial
      contamination, pathogen reduction and developments in the field of platelet
      biology will increase blood safety.

PMID- 19744889
TI  - Evaluation of consultation training in hypertension care.
AB  - BACKGROUND: Nurses in hypertension care play an important role in minimising the
      risk factors for cardiovascular diseases, but this care can be improved. AIM: To
      evaluate the content of nurses' consultations with hypertensive patients before
      and after consultation training. METHODS: Nineteen nurses from a randomised study
      of nurse-led hypertension clinics at health centres received three days of
      residential training in patient-centred counselling and cardiovascular
      prevention. To assess the result, two consultations with hypertensive patients in
      clinical practice before and after the training were audio-recorded. Content
      analysis was used for the analysis. RESULTS: Diet and exercise were the most
      frequent topics in the consultations both before and after the training.
      Discussions about alcohol and the patient's responsibility for treatment
      increased after the training. The time spent talking about various issues, other
      health problems, history and appointment scheduling decreased in the
      consultations after the training. CONCLUSION: After the consultation training,
      the nurses succeeded in emphasising important issues for risk factor control to a
      greater extent.

PMID- 19744890
TI  - Initial symptoms, precipitant factors, and techniques to control epileptic
      seizures: the carer's perspective.
AB  - Subjective experiences of seizures and events that occur prior to seizures may be
      useful in assisting health professionals to devise treatment plans tailored to
      the individual. The aim of this study was to investigate carers' knowledge of
      their patients' preseizure activity. Of 240 questionnaires mailed out to
      registrants on an epilepsy research database, 78 were anonymously returned
      (32.5%). Participants were aged between 18 and 89, with a mean age of 50.94 years
      (SD=17.23), and 82.1% were female. Of 78 participants, 74.4% reported that their
      patients experienced at least one symptom prior to a seizure, 88.5% reported that
      their patients experienced at least one seizure as a result of a specific event,
      and 56.4% reported that their patients had tried at least one technique to stop a
      seizure. The rates reported are comparable to those reported in other studies
      measuring responses from people with epilepsy.

PMID- 19744891
TI  - Unilateral focal burn injury is followed by long-lasting bilateral allodynia and
      neuronal hyperexcitability in spinal cord dorsal horn.
AB  - Pain after burn injury can be intense and long lasting. Treatment is often
      ineffective, and there is a need for increased knowledge of the underlying pain
      mechanisms. In the present study, we established a unilateral partial-thickness
      burn injury model, which produces ipsilateral mechanical allodynia soon after
      injury, followed by contralateral allodynia. Chronic bilateral allodynia lasts up
      to 8 weeks postinjury in this model. In addition to the change in pain behavior,
      electrophysiological analyses showed that dorsal horn neurons become
      hyperexcitable and display significantly increased evoked activity with enlarged
      receptive fields, initially on the side ipsilateral to the injury, and
      subsequently on both sides of the spinal cord. It is known that, following nerve
      injury, activation of p38 mitogen-activated protein kinase (MAPK) pathways within
      spinal microglia contributes to the pathogenesis of pain. In our burn injury
      model, rapid and prolonged activation of phospho-p38-expressing microglia occurs
      bilaterally in the spinal cord dorsal horn. Taken together, these data
      demonstrate that a unilateral peripheral burn injury can produce long-lasting
      allodynia that can spread to the contralateral limb, together with dorsal horn
      neuronal hyperexcitability and microglial activation on both ipsilateral and
      contralateral sides of the spinal cord. Our results suggest that central
      neuropathic mechanisms can contribute to pain after burn injury. PERSPECTIVE:
      Mechanisms contributing to pain following burn injury are incompletely
      understood. In a novel animal model of burn injury, we have demonstrated
      hyperexcitability of second-order sensory neurons, activation of microglia, and
      chronic bilateral pain following the burn injury. This work identifies potential
      therapeutic targets to alleviate pain after burn injury.

PMID- 19744892
TI  - Initial clinical experience with the Strut-Adjusted Volume Implant brachytherapy
      applicator for accelerated partial breast irradiation.
AB  - PURPOSE: Accelerated partial breast irradiation is becoming increasingly popular.
      The Cianna single-entry high-dose-rate applicator, Strut-Adjusted Volume Implant
      (SAVI, Cianna Medical, Aliso Viejo, CA), contains peripheral struts allowing
      greater planning flexibility for small-breasted women, technically easier
      insertion, and normal tissue exposure minimization. This study evaluates early
      clinical experience. METHODS AND MATERIALS: Thirty patients treated with the SAVI
      with a median followup of 12 months were evaluated. The median age was 59.5.
      Tumor size averaged 0.9cm. Fifteen cancers were ductal carcinoma in situ (50%), 1
      was invasive lobular (3.3%), 4 were tubular (6.7%), and the rest infiltrating
      ductal (40%). Most of them were estrogen receptor (ER) positive (90%). Nine women
      (30%) were premenopausal. RESULTS: Dosimetry was outstanding with median V90,
      V150, and V200 of 96.2%, 24.8, and 12.8cc. There were no symptomatic seromas, and
      one report of asymptomatic fat necrosis seen on mammogram at 1 year. In patients
      who had skin spacing of less than 1cm, the median skin dose was 245cGy/fraction.
      The median rib and lung dose per fraction for those patients with either
      structure less than 1cm was 340 and 255cGy (75% of prescribed dose),
      respectively. There have been no local recurrences to date. CONCLUSIONS: Early
      clinical experience with the SAVI demonstrates the ease of placement of a single
      entry brachytherapy device combined with the increased dose modulation of
      interstitial brachytherapy. Dose to normal structures has remained exceedingly
      low. Almost half of evaluated patients were not candidates for other single-entry
      brachytherapy devices because of skin spacing or breast size, demonstrating an
      expansion of candidates for single-entry partial breast brachytherapy.

PMID- 19744894
TI  - Multifunctional mechanosensitive neurons in the enteric nervous system.
AB  - One of the most intriguing abilities of the gut is to function in isolation. This
      is possible because the gut's own nervous system, the enteric nervous system,
      contains the necessary elements to control reflex behaviors. Much progress has
      been made in identifying those neurons that encode mechanical or chemical
      stimuli. Thus, muscle behaviors in the small and large intestines depend on
      mechanosensitive neurons which encode a variety of mechanical stimuli, ranging
      from brief deformation of the neurons soma or processes to sustained tissue
      stretch. Mechanosensitivity has been recorded in a wide variety of neurons which
      behave like rapid or slowly adapting mechanosensors. Strikingly, mechanosensitive
      neurons do not appear to belong to a distinct class of highly specialised neurons
      but rather differ in their electrophysiology, neurochemistry and morphology.
      While some mechanosensitive neurons may respond to one stimulus type others
      appear to be polymodal. Available data would suggest that mechanosensitive
      enteric neurons are multitasking and hence belong to multifunctional circuits.
      This review summarises the main arguments in favour of this concept, discusses
      the stimulus modalities, the response patterns and the functional role of
      mechanosensitive enteric neurons and concludes with identifying future
      challenges.

PMID- 19744893
TI  - Temporal lobe functional activity and connectivity in young adult APOE
      varepsilon4 carriers.
AB  - BACKGROUND: We sought to determine if the APOE epsilon4 allele influences both
      the functional activation and connectivity of the medial temporal lobes (MTLs)
      during successful memory encoding in young adults. METHODS: Twenty-four healthy
      young adults, i.e., 12 carriers and 12 noncarriers of the APOE epsilon4 allele,
      were scanned in a subsequent-memory paradigm, using event-related functional
      magnetic resonance imaging. The neuroanatomic correlates of successful encoding
      were measured as greater neural activity for subsequently remembered versus
      forgotten task items, or in short, encoding success activity (ESA). Group
      differences in ESA within the MTLs, as well as whole-brain functional
      connectivity with the MTLs, were assessed. RESULTS: In the absence of demographic
      or performance differences, APOE epsilon4 allele carriers exhibited greater
      bilateral MTL activity relative to noncarriers while accomplishing the same
      encoding task. Moreover, whereas epsilon4 carriers demonstrated a greater
      functional connectivity of ESA-related MTL activity with the posterior cingulate
      and other peri-limbic regions, reductions in overall connectivity were found
      across the anterior and posterior cortices. CONCLUSIONS: These results suggest
      that the APOE varepsilon4 allele may influence not only functional activations
      within the MTL, but functional connectivity of the MTLs to other regions
      implicated in memory encoding. Enhanced functional connectivity of the MTLs with
      the posterior cingulate in young adult epsilon4 carriers suggests that APOE may
      be expressed early in brain regions known to be involved in Alzheimer's disease,
      long before late-onset dementia is a practical risk or consideration. These
      functional connectivity differences may also reflect pleiotropic effects of APOE
      during early development.

PMID- 19744895
TI  - Quantitation of catalpol in rat plasma by liquid chromatography/electrospray
      ionization tandem mass spectrometry and its pharmacokinetic study.
AB  - A sensitive, rapid and specific liquid chromatography/tandem mass spectrometry
      (LC/MS/MS) assay has been established for the quantitation of catalpol in rat
      plasma. Plasma samples were treated by precipitating protein with methanol and
      were chromatographed by a Diamonsil C(18) column (150 mm x 4.6 mm I.D., 5 microm)
      with the mobile phase consisting of methanol and 10 mM ammonium formate (30:70,
      v/v). The selected reaction monitoring (SRM) transitions were performed at m/z
      380.1-->183.0 for catalpol and m/z 364.3-->167.0 for aucubin (IS) in the positive
      ion mode with electrospray ionization (ESI) source. Calibration curve was linear
      over the concentration range of 10-20,000 ng/mL. The mean recovery was 76.5+/
      5.2% and the matrix effect ranged from -5.1 to 13.0%. The intra- and inter-day
      precisions were less than 6.3 and 14.6%, respectively, and the accuracy was
      within +/-5.6%. Catalpol was stable in possible conditions of storing and
      handling. The validated method has been successfully applied to determine the
      plasma concentration of catalpol for a pharmacokinetic study of catalpol after
      oral administration of 50 mg/kg to rats.

PMID- 19744896
TI  - Analysis of thiols.

PMID- 19744897
TI  - Development and validation of a reversed-phase high-performance liquid
      chromatographic method for quantification of peptide dendrimers in human skin
      permeation experiments.
AB  - The aim of the present work was to develop and validate a simple RP-HPLC method
      with UV detection to quantify peptide dendrimers in skin permeation experiments.
      Six dendrimers of varying positive charges (4(+), 8(+) and 16(+)) containing
      either histidine or arginine as terminal aminoacids were prepared by solid phase
      peptide synthesis. Mobile phase containing 0.02% (v/v) heptafluorobutyric acid in
      90% acetonitrile-water was capable of separating all dendrimers from interfering
      peaks of receptor fluid. For the calibration of each dendrimer, a different
      dendrimer from the same class was selected as the internal standard. The results
      of preliminary human skin permeation studies showed that the developed analytical
      method can be successfully used for the quantification of cationic
      poly(aminoacid)-based dendrimers in skin permeation experiments.

PMID- 19744898
TI  - Rapid determination of telmisartan in human plasma by HPLC using a monolithic
      column with fluorescence detection and its application to a bioequivalence study.
AB  - A rapid HPLC method using a monolithic column with fluorescence detection has
      been developed for determination of telmisartan in human plasma. Sample
      preparation was done by protein precipitation with acetonitrile and naproxen was
      used as IS. The compounds were detected by fluorescence detection, using an
      excitation wavelength of 300 nm and emission wavelength of 385 nm. Calibration
      curves of telmisartan were linear in the range of 1-200 ng/mL. The assay was high
      throughput, sensitive and precise, and it was successfully applied to a
      bioequivalence study of two formulations of telmisartan.

PMID- 19744899
TI  - Lack of specificity for the analysis of raltegravir using online sample clean-up
      liquid chromatography-electrospray tandem mass spectrometry.
AB  - BACKGROUND: Raltegravir is the first antiretroviral agent to target the human
      immunodeficiency virus-1 (HIV-1) integrase. It is indicated, in association with
      other antiretrovirals, in the treatment of acquired immunodeficiency syndrome
      (AIDS) in antiretroviral treatment-experienced adult patients with viral
      resistance. To evaluate the feasibility of raltegravir therapeutic drug
      monitoring, we developed a rapid and specific analytical method for the
      quantification of raltegravir in human plasma by online sample clean-up liquid
      chromatography-tandem mass spectrometry (LC-MS/MS). METHODS: After protein
      precipitation (with 100 microL of acetonitrile/methanol (50/50)) of 25 microL of
      plasma, fast online matrix-clean-up was performed using a column switching
      program. The chromatographic step was optimized to separate raltegravir and its
      glucuronide metabolite (G-raltegravir). Multiple reaction monitoring (MRM) was
      used for detection of raltegravir and G-raltegravir. In the absence of G
      raltegravir standard, G-raltegravir identification was confirmed by beta
      glucuronidase pre-treatment. RESULTS: A total analysis of 3.8 min was needed to
      separate raltegravir to G-raltegravir. The method was linear between 10 and 3000
      ng/mL for raltegravir. Analytical recovery was 94+/-1%. Variation coefficients
      ranged between 5% and 8.4%. Pre-treatment of plasma from a patient under
      raltegravir treatment with beta-glucuronidase suppressed G-raltegravir peak.
      CONCLUSION: We describe a fast online LC-MS/MS assay that is valid and reliable
      for the quantification of raltegravir, despite the lack of specificity that could
      occur in MRM scanning mode experiments.

PMID- 19744900
TI  - Direct determination of N-methyl-2-pyrrolidone metabolites in urine by HPLC
      electrospray ionization-MS/MS using deuterium-labeled compounds as internal
      standard.
AB  - N-methyl-2-pyrrolidone (NMP) has been used in many industries and biological
      monitoring of NMP exposure is preferred to atmospheric monitoring in occupational
      health. We developed an analytical method that did not include solid phase
      extraction (SPE) but utilized deuterium-labeled compounds as internal standard
      for high-performance liquid chromatography-electrospray ionization-mass
      spectrometry using a C30 column. Urinary concentrations of NMP and its known
      metabolites 5-hydoxy-N-methyl-2-pyrrolidone (5-HNMP), N-methyl-succinimide (MSI),
      and 2-hydroxy-N-methylsuccinimide (2-HMSI) were determined in a single run. The
      method provided baseline separation of these compounds. Their limits of detection
      in 10-fold diluted urine were 0.0001, 0.006, 0.008, and 0.03 mg/L, respectively.
      Linear calibration covered a biological exposure index (BEI) for urinary
      concentration. The within-run and total precisions (CV, %) were 5.6% and 9.2% for
      NMP, 3.4% and 4.2% for 5-HNMP, 3.7% and 6.0% for MSI, and 6.5% and 6.9% for 2
      HMSI. The method was evaluated using international external quality assessment
      samples, and urine samples from workers exposed to NMP in an occupational area.

PMID- 19744901
TI  - Simultaneous determination of AZD1152 (prodrug) and AZD1152-hydroxyquinazoline
      pyrazol anilide by reversed phase liquid chromatography.
AB  - A simple, selective and sensitive reversed phase liquid chromatography method
      utilizing ultraviolet detection has been developed and validated for the
      simultaneous determination of the prodrug AZD1152 and its active product AZD1152
      hydroxyquinazoline pyrazol anilide (hQPA) in human and mouse plasma and mouse
      tissues. Isocratic separation was achieved using an 5mum UptiSphere HDO C-18
      column (150 mm x 4.6 mm) with guard column in combination with a mobile phase
      comprised of phosphate buffered water (50 mM; pH 3.4) and acetonitrile (81.5:
      18.5; v/v). UV detection at 318 nm was used. Sample preparation involved a single
      step protein precipitation with ethanol. Ex vivo conversion of AZD1152 by
      endogenous phosphatases was prevented by immediate cooling of the samples in ice
      water and addition of sodium fluoride and EDTA. The validation parameters
      included specificity, recovery, accuracy, precision, sensitivity and stability.
      The lower limit of quantification in human plasma for AZD1152 and hQPA was 25
      ng/ml. The applicability of the method was demonstrated by successful
      determination of AZD1152 and hQPA in human plasma and in plasma, brain, liver,
      kidney and ileum samples from mice dosed with AZD1152.

PMID- 19744902
TI  - [Miller Fisher syndrome in paediatrics: A description of 3 cases].

PMID- 19744903
TI  - [Tuberculosis due to Mycobacterium bovis in Murcia].
AB  - Tuberculosis due to Mycobacterium bovis is a common disease in developing
      countries, due to its reservoir and most common forms of transmission.
      Extrapulmonary cases are not uncommon. This fact and the exceptional nature of
      this mycobacterium, make the diagnosis difficult in our environment. The arrival
      of migrants from developing countries, where affected cattle and ingestion of
      contaminated products are frequent, we must be on the alert for an early
      diagnosis and adequate treatment. We report three cases diagnosed in our region,
      both with extrapulmonary presentations (cervical lymphadenitis and abdominal
      tuberculosis), and analyze the present situation of this illness in Spanish
      livestock, and the influence of immigration on it.

PMID- 19744904
TI  - [Shock as initial presentation of Kawasaki disease].

PMID- 19744905
TI  - Necrosis of nose skin after varicella zoster infection: a case report.
AB  - Varicella zoster virus (VZV) is the causal agent of varicella (chickenpox) and
      herpes zoster (shingles). Primary VZV infection is a common childhood disease,
      but elderly patients and those having a compromised immune system are also at
      risk. We present the case of progressive necrosis of the nose skin in a patient
      with a compromised immune system and a generalised VZV infection. During the
      course of his hospital stay and follow-up, the lesion gradually improved with
      conservative treatment.

PMID- 19744906
TI  - Electronic tracking system and wandering in Alzheimer's disease: a case study.
AB  - INTRODUCTION: Wandering is a behavioural disorder, which occurs in Alzheimer's
      disease or other dementia. People who wander are at risk of physical harm and
      untimely death. Moreover, wandering behaviour causes a lot of stress to the
      caregivers. In the last few years, different geolocation devices have been
      developed in order to minimise risk and manage unsafe wandering. These detection
      systems rarely meet patients and caregivers' needs because they are not involved
      in the devices building process. AIM: The aim is to explore the needs and
      perceptions of wandering persons and their caregivers towards existing tracking
      devices as well as their acceptability and usability. This paper reports a dyad
      case. MATERIALS: The tracking system tested is presented as a mobile Global
      Positioning System (GPS) receiver-shaped, including function of telephony and
      data transfer via GSM/GPRS. METHOD: Dyad patient/caregiver expressed their needs
      and perceptions towards tracking devices and gave their impressions about the
      functioning of the tested device at the end of the test. RESULTS: The patient
      focused on the device's shape which he found too voluminous and unaesthetic, and
      was unable to give an opinion about the device's functioning. The spouse
      highlighted malfunctions and usage difficulties, which made the device not
      appropriate to her needs. CONCLUSION: Involving end-users in the co-design of new
      technologies is necessary for building tailored devices. Moreover, in this area
      of dementia care, the person-centred approach is essential to a tailored
      wandering management.

PMID- 19744907
TI  - Long-term risk of receiving a total hip replacement in cancer patients.
AB  - AIM: To investigate whether cancer patients have an increased risk of receiving a
      total hip replacement compared to the standard population of Norway. MATERIALS
      AND METHODS: By linking of The Cancer Register of Norway and The Norwegian
      Arthroplasty Register we obtained information on cancer diagnoses (type, date of
      diagnosis), total hip arthroplasties and date of death for all patients living in
      Norway. This includes 741,901 patients categorized into three groups: 652,197
      patients with at least one cancer diagnosis but no hip arthroplasties, 72,469
      patients with at least one hip arthroplasty but no cancer diagnosis and 17,235
      patients who have at least one cancer diagnosis and at least one hip
      arthroplasty. Within this latter group, 8563 individuals had been diagnosed with
      cancer prior to a total hip arthroplasty. Statistical methods applied in this
      study were Cox interval censored regression models and standardized incidence
      ratios (SIR). RESULTS: Cancer patients had a slightly increased risk of receiving
      a total hip arthroplasty compared to the Norwegian population (SIR=1.15 (95% CI,
      1.12-1.17)). For primary tumours located cranially to the pelvic area there was
      no significant increase in risk for hip arthroplasty. An exception was breast
      cancer (SIR=1.13 (95% CI 1.08-1.18)). Cancer located in the pelvic region
      (SIR=1.20 (95% CI 1.16-1.24)), malignant lymphoma (SIR=1.30 (95% CI 1.15-1.46))
      and leukaemia (SIR=1.17 (95% CI 1.01-1.34)) had an increased risk for receiving a
      total hip arthroplasty. CONCLUSION: Cancer survivors, mainly those with pelvic
      and lympho-hematological malignancies, have a small statistically significant
      increase in risk for receiving total hip arthroplasty.

PMID- 19744908
TI  - On normalized MSE analysis of speech fundamental frequency in the cochlear
      implant-like spectrally reduced speech.
AB  - In this paper, we present a quantitative study on the speech fundamental
      frequency (F0) of the cochlear implant-like spectrally reduced speech (SRS). The
      SRS was synthesized from the subband amplitude and frequency modulations (AM and
      FM) of original clean speech utterances selected from the TI-digits database. The
      SRS synthesis algorithm was derived from the frequency amplitude modulation
      encoding (FAME) strategy, proposed by Nie et al., 2005. The normalized mses
      (NMSEs), calculated between the F0 of the original clean speech and that of the
      SRSs, were analyzed. The NMSEs analysis of F0 revealed the greater F0 distortion
      in the AM-based SRS, which is the acoustic simulation of present-day cochlear
      implants, compared to the FAME-based SRS. This evidence supports the fact that
      current cochlear implant users have difficulty in the speaker recognition task as
      reported by Zeng et al., 2005. Further, the analysis results showed that it is
      better to keep the rapidly varying FM components to reduce the F0 distortion in
      the FAME-based SRS at low spectral resolution.

PMID- 19744909
TI  - A regulator for pressure-controlled total-liquid ventilation.
AB  - Total-liquid ventilation (TLV) is an innovative experimental method of mechanical
      assisted ventilation in which lungs are totally filled and then ventilated with a
      tidal volume of perfluorochemical liquid by using a dedicated liquid ventilator.
      Such a novel medical device must resemble other conventional ventilators: it must
      be able to conduct controlled-pressure ventilation. The objective was to design a
      robust controller to perform pressure-regulated expiratory flow and to implement
      it on our latest liquid-ventilator prototype (Inolivent-4). Numerical
      simulations, in vitro experiments, and in vivo experiments in five healthy term
      newborn lambs have demonstrated that it was efficient to generate expiratory
      flows while avoiding collapses. Moreover, the in vivo results have demonstrated
      that our liquid ventilator can maintain adequate gas exchange, normal acid-base
      equilibrium, and achieve greater minute ventilation, better oxygenation and CO2
      extraction, while nearing flow limits. Hence, it is our suggestion to perform
      pressure-controlled ventilation during expiration with minute ventilation equal
      or superior to 140 mL x min(-1) x kg(-1) in order to ensure PaCO2 below 55 mmHg.
      From a clinician's point of view, pressure-controlled ventilation greatly
      simplifies the use of the liquid ventilator, which will certainly facilitate its
      introduction in intensive care units for clinical applications.

PMID- 19744910
TI  - Multiobjective optimization of an electrostimulative acetabular revision system.
AB  - In this paper, we present a new approach for the enhancement of the bone
      proliferation rate by electrostimulation in the acetabular region. Based on the
      complex tissue structure in this area, the electric field distributions were
      computed by numerical means using a model based on high-resolution computed
      tomography scans of the acetabular area. This results in a complex, nonlinear,
      and discrete optimization problem. Therefore, an adapted algorithm was developed
      to reduce the computational effort in the order of several magnitudes. We divided
      the procedure into two stages: data extraction and a subsequent optimization
      process. The used optimization algorithm utilizes an evolutionary concept and a
      multidimensional definition of optimality for different, partly contradictive
      objective functions. Finally, we present first optimization results for different
      stimulation situations.

PMID- 19744911
TI  - Intersection based motion correction of multislice MRI for 3-D in utero fetal
      brain image formation.
AB  - In recent years, postprocessing of fast multislice magnetic resonance imaging
      (MRI) to correct fetal motion has provided the first true 3-D MR images of the
      developing human brain in utero. Early approaches have used reconstruction based
      algorithms, employing a two-step iterative process, where slices from the
      acquired data are realigned to an approximate 3-D reconstruction of the fetal
      brain, which is then refined further using the improved slice alignment. This two
      step slice-to-volume process, although powerful, is computationally expensive in
      needing a 3-D reconstruction, and is limited in its ability to recover subvoxel
      alignment. Here, we describe an alternative approach which we term slice
      intersection motion correction (SIMC), that seeks to directly co-align multiple
      slice stacks by considering the matching structure along all intersecting slice
      pairs in all orthogonally planned slices that are acquired in clinical imaging
      studies. A collective update scheme for all slices is then derived, to
      simultaneously drive slices into a consistent match along their lines of
      intersection. We then describe a 3-D reconstruction algorithm that, using the
      final motion corrected slice locations, suppresses through-plane partial volume
      effects to provide a single high isotropic resolution 3-D image. The method is
      tested on simulated data with known motions and is applied to retrospectively
      reconstruct 3-D images from a range of clinically acquired imaging studies. The
      quantitative evaluation of the registration accuracy for the simulated data sets
      demonstrated a significant improvement over previous approaches. An initial
      application of the technique to studying clinical pathology is included, where
      the proposed method recovered up to 15 mm of translation and 30 degrees of
      rotation for individual slices, and produced full 3-D reconstructions containing
      clinically useful additional information not visible in the original 2-D slices.

PMID- 19744912
TI  - Adaptive neural control design for nonlinear distributed parameter systems with
      persistent bounded disturbances.
AB  - In this paper, an adaptive neural network (NN) control with a guaranteed
      L(infinity)-gain performance is proposed for a class of parabolic partial
      differential equation (PDE) systems with unknown nonlinearities and persistent
      bounded disturbances. Initially, Galerkin method is applied to the PDE system to
      derive a low-order ordinary differential equation (ODE) system that accurately
      describes the dynamics of the dominant (slow) modes of the PDE system.
      Subsequently, based on the low-order slow model and the Lyapunov technique, an
      adaptive modal feedback controller is developed such that the closed-loop slow
      system is semiglobally input-to-state practically stable (ISpS) with an
      L(infinity)-gain performance. In the proposed control scheme, a radial basis
      function (RBF) NN is employed to approximate the unknown term in the derivative
      of the Lyapunov function due to the unknown system nonlinearities. The outcome of
      the adaptive L(infinity)-gain control problem is formulated as a linear matrix
      inequality (LMI) problem. Moreover, by using the existing LMI optimization
      technique, a suboptimal controller is obtained in the sense of minimizing an
      upper bound of the L(infinity)-gain, while control constraints are respected.
      Furthermore, it is shown that the proposed controller can ensure the semiglobal
      input-to-state practical stability and L(infinity)-gain performance of the closed
      loop PDE system. Finally, by applying the developed design method to the
      temperature profile control of a catalytic rod, the achieved simulation results
      show the effectiveness of the proposed controller.

PMID- 19744914
TI  - Discriminative orthogonal neighborhood-preserving projections for classification.
AB  - Orthogonal neighborhood-preserving projection (ONPP) is a recently developed
      orthogonal linear algorithm for overcoming the out-of-sample problem existing in
      the well-known manifold learning algorithm, i.e., locally linear embedding. It
      has been shown that ONPP is a strong analyzer of high-dimensional data. However,
      when applied to classification problems in a supervised setting, ONPP only
      focuses on the intraclass geometrical information while ignores the interaction
      of samples from different classes. To enhance the performance of ONPP in
      classification, a new algorithm termed discriminative ONPP (DONPP) is proposed in
      this paper. DONPP 1) takes into account both intraclass and interclass
      geometries; 2) considers the neighborhood information of interclass
      relationships; and 3) follows the orthogonality property of ONPP. Furthermore,
      DONPP is extended to the semisupervised case, i.e., semisupervised DONPP
      (SDONPP). This uses unlabeled samples to improve the classification accuracy of
      the original DONPP. Empirical studies demonstrate the effectiveness of both DONPP
      and SDONPP.

PMID- 19744915
TI  - Modeling a student's behavior in a tutorial-like system using learning automata.
AB  - This paper presents a new philosophy to model the behavior of a student in a
      tutorial- like system using learning automata (LAs). The model of the student in
      our system is inferred using a higher level LA, referred to as a meta-LA , which
      attempts to characterize the learning model of the students (or student
      simulators), while the latter use the tutorial-like system. The meta-LA , in
      turn, uses LAs as a learning mechanism to try to determine if the student in
      question is a fast, normal, or slow learner. The ultimate long-term goal of the
      exercise is the following: if the tutorial- like system can understand how the
      student perceives and processes knowledge, it will be able to customize the way
      by which it communicates the knowledge to the student to attain an optimal
      teaching strategy. The proposed meta-LA scheme has been tested for numerous
      environments, including the established benchmarks, and the results obtained are
      remarkable. Indeed, to the best of our knowledge, this is the first published
      result that infers the learning model of an LA when it is externally treated as a
      black box, whose outputs are the only observable quantities. Additionally, our
      paper represents a new class of multiautomata systems, where the meta-LA
      synchronously communicates with the students, also modeled using LAs. The meta
      LA's environment "observes" the progress of the student LA, and the response of
      the latter to the meta-LA actions is based on these observations. This paper also
      discusses the learning system implications of such a meta-LA.

PMID- 19744916
TI  - Long micro-channel electrode arrays: a novel type of regenerative peripheral
      nerve interface.
AB  - We have demonstrated that micro-channel electrode arrays with 100 microm x 100
      microm cross-section channels support axon regeneration well, and that micro
      channels of similar calibre and up to 5 mm long can support axon regeneration and
      vascularisation. They may be microfabricated using silicon, silicone, or
      polyimide and thin metal films to form 3-D bundles of long micro-channels. Arrays
      of "mini-nerves," i.e., miniature nerve fascicles with their own blood vessels,
      successfully grew through implants 0.5-5 mm long. Furthermore, guiding the
      regenerating nerve fibres into the small insulating channels allows for a
      significant increase of the extracellular (recordable) amplitude of action
      potentials, which promises considerable improvement for in vivo
      electrophysiology.

PMID- 19744917
TI  - [Involvement of human papillomavirus in upper aero-digestive tracts cancers].
AB  - Human papillomavirus (HPV) is one of the most common causes of sexually
      transmitted infection in the world. France and Belgium present one of the highest
      incidence of head and neck squamous cell carcinomas (HNSCC) worldwide. Besides,
      considering only the male population, HNSCCs represent the fourth most frequent
      cancer after prostate, lung and colon cancers. Although the causal link between
      high-risk HPVs and cervical carcinoma is well established, the implication of
      this viral infection in HNSCC remains debatable. Here, we discuss current
      knowledge concerning the HPV implication in HNSCCs. Based on our literature
      review, 20 to 25% of HNSCCs could be associated with oncogenic HPVs, in
      particular HPV type 16. The oropharynx--more precisely the tonsil--is the head
      and neck location presenting the highest incidence of HPV infection. Moreover, a
      clear increase of tonsillar carcinoma incidence has been described. As observed
      in cervical carcinomas, HPV positive HNSCCs are sexually transmitted and
      characterized by alterations of p53 and pRb signalling pathways. Several studies
      have shown that HPV positive subgroup presented better prognosis particularly if
      these patients overexpressed p16INK4. New studies regarding HPV status in HNSCCs
      are warranted to provide a rationale for large scale HPV vaccination in young
      male populations.

PMID- 19744918
TI  - [Estimation of individual breast cancer risk: relevance and limits of risk
      estimation models].
AB  - Several risk estimation models for breast or ovarian cancers have been developed
      these last decades. All these models take into account the family history, with
      different levels of sophistication. Gail model was developed in 1989 taking into
      account the family history (0, 1 or > or = 2 affected relatives) and several
      environmental factors. In 1990, Claus model was the first to integrate explicit
      assumptions about genetic effects, assuming a single gene dominantly inherited
      occurring with a low frequency in the population. BRCAPRO model, posterior to the
      identification of BRCA1 and BRCA2, assumes a restricted transmission with only
      these two dominantly inherited genes. BOADICEA model adds the effect of a
      polygenic component to the effect of BRCA1 and BRCA2 to explain the residual
      clustering of breast cancer. At last, IBIS model assumes a third dominantly
      inherited gene to explain this residual clustering. Moreover, this model
      incorporates environmental factors. We applied the Claus, BRCAPRO, BOADICEA and
      IBIS models to four clinical situations, corresponding to more or less heavy
      family histories, in order to study the consistency of the risk estimates. The
      three more recent models (BRCAPRO, BOADICEA and IBIS) gave the closer
      estimations. These estimates could be useful in clinical practice in front of
      complex analysis of breast and/or ovarian cancers family history.

PMID- 19744919
TI  - [Locally advanced head and neck cancers: recommendations of an expert panel and
      perspectives for the use of TPF regimen (docetaxel, cisplatin and fluoro-uracil)
      as induction therapy].
AB  - PURPOSE: The purpose of the present article was to evaluate indications,
      regimens, treatment modalities, and predictive factors of response to treatment
      in locally advanced squamous cell carcinoma of the head and neck (SCCHN).
      METHODS: An expert panel including otolaryngology and head and neck surgery
      specialists, oncologists, radiotherapists and biologists analyzed the literature
      providing a synthesis and giving some recommendations. SYNTHESIS: Findings from
      the main randomized phase III trials highlight that the TPF regimen (docetaxel,
      cisplatin, fluorouracil) represent a preferential option when induction
      chemotherapy is indicated in either operable or non-operable patients. Given the
      potential fragility of patients presenting with SCCHN, treatment modalities in
      routine use require applying preventive measures and tailored follow-up according
      to each patient's profile. As regards predictive factors of response to TPF
      regimen, no factor is currently validated, but ongoing trials should provide
      better knowledge. CONCLUSION: Progresses in induction chemotherapy have allowed
      improving the prognosis of patients with locally advanced SCCHN. The TPF regimen
      represents a major improvement in this indication, and ongoing strategic clinical
      trials should refine its indications.

PMID- 19744920
TI  - The National Niemann-Pick Type C1 Disease Database: correlation of lipid
      profiles, mutations, and biochemical phenotypes.
AB  - Niemann-Pick type C1 disease (NPC1) is an autosomal recessive lysosomal storage
      disorder characterized by neonatal jaundice, hepatosplenomegaly, and progressive
      neurodegeneration. The present study provides the lipid profiles, mutations, and
      corresponding associations with the biochemical phenotype obtained from NPC1
      patients who participated in the National NPC1 Disease Database. Lipid profiles
      were obtained from 34 patients (39%) in the survey and demonstrated significantly
      reduced plasma LDL cholesterol (LDL-C) and increased plasma triglycerides in the
      majority of patients. Reduced plasma HDL cholesterol (HDL-C) was the most
      consistent lipoprotein abnormality found in male and female NPC1 patients across
      age groups and occurred independent of changes in plasma triglycerides. A subset
      of 19 patients for whom the biochemical severity of known NPC1 mutations could be
      correlated with their lipid profile showed a strong inverse correlation between
      plasma HDL-C and severity of the biochemical phenotype. Gene mutations were
      available for 52 patients (59%) in the survey, including 52 different mutations
      and five novel mutations (Y628C, P887L, I923V, A1151T, and 3741_3744delACTC).
      Together, these findings provide novel information regarding the plasma
      lipoprotein changes and mutations in NPC1 disease, and suggest plasma HDL-C
      represents a potential biomarker of NPC1 disease severity.

PMID- 19744922
TI  - Interaction domain on thioredoxin for Pseudomonas aeruginosa 5'-adenylylsulfate
      reductase.
AB  - NMR spectroscopy has been used to map the interaction domain on Escherichia coli
      thioredoxin for the thioredoxin- dependent 5'-adenylylsulfate reductase from
      Pseudomonas aeruginosa (PaAPR). Seventeen thioredoxin amino acids, all clustered
      around Cys-32 (the more surface-exposed of the two active-site cysteines), have
      been located at the PaAPR binding site. The center of the binding domain is
      dominated by nonpolar amino acids, with a smaller number of charged and polar
      amino acids located on the periphery of the site. Twelve of the amino acids
      detected by NMR have non-polar, hydrophobic side chains, including one aromatic
      amino acid (Trp-31). Four of the thioredoxin amino acids at the PaAPR binding
      site have polar side chains (Lys-36, Asp-61, Gln-62 and Arg-73), with three of
      the four having charged side chains. Site-directed mutagenesis experiments have
      shown that replacement of Lys-36, Asp-61, and Arg-73 and of the absolutely
      conserved Trp-31 significantly decreases the V(max) for the PaAPR-catalyzed
      reduction of 5'-adenylylsulfate, with E. coli thioredoxin serving as the electron
      donor. The most dramatic effect was observed with the W31A variant, which showed
      no activity as a donor to PaAPR. Although the thiol of the active-site Cys-256 of
      PaAPR is the point of the initial nucleophilic attack by reduced thioredoxin,
      mutagenic replacement of Cys-256 by serine has no effect on thioredoxin binding
      to PaAPR.

PMID- 19744923
TI  - Furanose-specific sugar transport: characterization of a bacterial
      galactofuranose-binding protein.
AB  - The widespread utilization of sugars by microbes is reflected in the diversity
      and multiplicity of cellular transporters used to acquire these compounds from
      the environment. The model bacterium Escherichia coli has numerous transporters
      that allow it to take up hexoses and pentoses, which recognize the more abundant
      pyranose forms of these sugars. Here we report the biochemical and structural
      characterization of a transporter protein YtfQ from E. coli that forms part of an
      uncharacterized ABC transporter system. Remarkably the crystal structure of this
      protein, solved to 1.2 A using x-ray crystallography, revealed that YtfQ binds a
      single molecule of galactofuranose in its ligand binding pocket. Selective
      binding of galactofuranose over galactopyranose was also observed using NMR
      methods that determined the form of the sugar released from the protein. The
      pattern of expression of the ytfQRTyjfF operon encoding this transporter mirrors
      that of the high affinity galactopyranose transporter of E. coli, suggesting that
      this bacterium has evolved complementary transporters that enable it to use all
      the available galactose present during carbon limiting conditions.

PMID- 19744924
TI  - Exonuclease function of human Mre11 promotes deletional nonhomologous end
      joining.
AB  - DNA double-stranded breaks (DSBs) are lethal if not repaired and are highly
      mutagenic if misrepaired. Nonhomologous end joining (NHEJ) is one of the major
      DSB repair pathways and can rejoin the DSB ends either precisely or with
      mistakes. Recent evidence suggests the existence of two NHEJ subpathways:
      conservative NHEJ (C-NHEJ), which does not require microhomology and can join
      ends precisely; and deletional NHEJ (D-NHEJ), which utilizes microhomology to
      join the ends with small deletions. Little is known about how these NHEJ
      subpathways are regulated. Mre11 has been implicated in DNA damage response, thus
      we investigated whether Mre11 function also extended to NHEJ. We utilized an
      intrachromosomal NHEJ substrate in which DSBs are generated by the I-SceI to
      address this question. The cohesive ends are fully complementary and were either
      repaired by C-NHEJ or D-NHEJ with similar efficiency. We found that disruption of
      Mre11 by RNA interference in human cells led to a 10-fold decrease in the
      frequency of D-NHEJ compared with cells with functional Mre11. Interestingly, C
      NHEJ was not affected by Mre11 status. Expression of wild type but not
      exonuclease-defective Mre11 mutants was able to rescue D-NHEJ in Mre11-deficient
      cells. Further mutational analysis suggested that additional mechanisms
      associated with methylation of Mre11 at the C-terminal glycine-arginine-rich
      domain contributed to the promotion of D-NHEJ by Mre11. This study provides new
      insights into the mechanisms by which Mre11 affects the accuracy of DSB end
      joining specifically through control of the D-NHEJ subpathway, thus illustrating
      the complexity of the Mre11 role in maintaining genomic stability.

PMID- 19744925
TI  - The HECT domain of the ubiquitin ligase Rsp5 contributes to substrate
      recognition.
AB  - Ubiquitin modification of endosomal membrane proteins is a signal for active
      inclusion into the Multivesicular Body (MVB) pathway, resulting in lysosomal
      degradation. However, the endosome represents a dynamic site of protein sorting
      with a majority of proteins destined for recycling, rather than MVB targeting.
      Substrate recognition by ubiquitin ligases is therefore highly regulated. We have
      investigated substrate recognition by the Nedd4 ortholog Rsp5 as a model for
      understanding ligase-substrate interactions. Rsp5 interacts directly with its
      substrate Cps1 via a novel interaction mode. Perturbation of this mode of
      interaction revealed a compensatory role for the Rsp5 adaptor Bsd2. These results
      highlight the ability of Rsp5 to interact with substrates via multiple
      modalities, suggesting additional mechanisms of regulating this interaction and
      relevant outcomes.

PMID- 19744926
TI  - Diacylglycerol kinase epsilon is selective for both acyl chains of phosphatidic
      acid or diacylglycerol.
AB  - The phosphatidylinositol (PI) cycle mediates many cellular events by controlling
      the metabolism of many lipid second messengers. Diacylglycerol kinase epsilon
      (DGK epsilon) has an important role in this cycle. DGK epsilon is the only DGK
      isoform to show inhibition by its product phosphatidic acid (PA) as well as
      substrate specificity for sn-2 arachidonoyl-diacylglycerol (DAG). Here, we show
      that this inhibition and substrate specificity are both determined by selectivity
      for a combination of the sn-1 and sn-2 acyl chains of PA or DAG, respectively,
      preferring the most prevalent acyl chain composition of lipids involved
      specifically in the PI cycle, 1-stearoyl-2-arachidonoyl. Although the difference
      in rate for closely related lipid species is small, there is a significant
      enrichment of 1-stearoyl-2-arachidonoyl PI because of the cyclical nature of PI
      turnover. We also show that the inhibition of DGK epsilon by PA is competitive
      and that the deletion of the hydrophobic segment and cationic cluster of DGK
      epsilon does not affect its selectivity for the acyl chains of PA or DAG. Thus,
      this active site not only recognizes the lipid headgroup but also a combination
      of the two acyl chains in PA or DAG. We propose a mechanism of DGK epsilon
      regulation where its dual acyl chain selectivity is used to negatively regulate
      its enzymatic activity in a manner that ensures DGK epsilon remains committed to
      the PI turnover cycle. This novel mechanism of enzyme regulation within a
      signaling pathway could serve as a template for the regulation of enzymes in
      other pathways in the cell.

PMID- 19744927
TI  - Identification of an iron-sulfur cluster that modulates the enzymatic activity in
      NarE, a Neisseria meningitidis ADP-ribosyltransferase.
AB  - In prokaryotes, mono-ADP-ribose transfer enzymes represent a family of exotoxins
      that display activity in a variety of bacterial pathogens responsible for causing
      disease in plants and animals, including those affecting mankind, such as
      diphtheria, cholera, and whooping cough. We report here that NarE, a putative ADP
      ribosylating toxin previously identified from Neisseria meningitidis, which
      shares structural homologies with Escherichia coli heat labile enterotoxin and
      toxin from Vibrio cholerae, possesses an iron-sulfur center. The recombinant
      protein was expressed in E. coli, and when purified at high concentration, NarE
      is a distinctive golden brown in color. Evidence from UV-visible
      spectrophotometry and EPR spectroscopy revealed characteristics consistent of an
      iron-binding protein. The presence of iron was determined by colorimetric method
      and by an atomic absorption spectrophotometer. To identify the amino acids
      involved in binding iron, a combination of site-directed mutagenesis and UV
      visible and enzymatic assays were performed. All four cysteine residues were
      individually replaced by serine. Substitution of Cys(67) and Cys(128) into serine
      caused a drastic reduction in the E(420)/E(280) ratio, suggesting that these two
      residues are essential for the formation of a stable coordination. This
      modification led to a consistent loss in ADP-ribosyltransferase activity, while
      decrease in NAD-glycohydrolase activity was less dramatic in these mutants,
      indicating that the correct assembly of the iron-binding site is essential for
      transferase but not hydrolase activity. This is the first observation suggesting
      that a member of the ADP-ribosyltransferase family contains an Fe-S cluster
      implicated in catalysis. This observation may unravel novel functions exerted by
      this class of enzymes.

PMID- 19744928
TI  - Toc receptor dimerization participates in the initiation of membrane
      translocation during protein import into chloroplasts.
AB  - The post-translational import of nucleus-encoded preproteins into chloroplasts
      occurs through multimeric translocons in the outer (Toc) and inner (Tic)
      membranes. The high fidelity of the protein import process is maintained by
      specific recognition of the transit peptide of preproteins by the coordinate
      activities of two homologous GTPase Toc receptors, Toc34 and Toc159. Structural
      and biochemical studies suggest that dimerization of the Toc receptors functions
      as a component of the mechanism to control access of preproteins to the membrane
      translocation channel of the translocon. We show that specific mutations that
      disrupted receptor dimerization in vitro reduced the rate of protein import in
      transgenic Arabidopsis compared with the wild type receptor. The mutations did
      not affect the GTPase activities of the receptors. Interestingly, these mutations
      did not decrease the initial preprotein binding at the receptors, but they
      reduced the efficiency of the transition from preprotein binding to membrane
      translocation. These data indicate that dimerization of receptors has a direct
      role in protein import and support a hypothesis in which receptor-receptor
      interactions participate in the initiation of membrane translocation of
      chloroplast preproteins as part of the molecular mechanism of GTP-regulated
      protein import.

PMID- 19744929
TI  - Human Naa50p (Nat5/San) displays both protein N alpha- and N epsilon
      acetyltransferase activity.
AB  - Protein acetylation is a widespread modification that is mediated by site
      selective acetyltransferases. KATs (lysine N(epsilon)-acetyltransferases), modify
      the side chain of specific lysines on histones and other proteins, a central
      process in regulating gene expression. N(alpha)-terminal acetylation occurs on
      the ribosome where the alpha amino group of nascent polypeptides is acetylated by
      NATs (N-terminal acetyltransferase). In yeast, three different NAT complexes were
      identified NatA, NatB, and NatC. NatA is composed of two main subunits, the
      catalytic subunit Naa10p (Ard1p) and Naa15p (Nat1p). Naa50p (Nat5) is physically
      associated with NatA. In man, hNaa50p was shown to have acetyltransferase
      activity and to be important for chromosome segregation. In this study, we used
      purified recombinant hNaa50p and multiple oligopeptide substrates to identify and
      characterize an N(alpha)-acetyltransferase activity of hNaa50p. As the preferred
      substrate this activity acetylates oligopeptides with N termini Met-Leu-Xxx-Pro.
      Furthermore, hNaa50p autoacetylates lysines 34, 37, and 140 in vitro, modulating
      hNaa50p substrate specificity. In addition, histone 4 was detected as a hNaa50p
      KAT substrate in vitro. Our findings thus provide the first experimental evidence
      of an enzyme having both KAT and NAT activities.

PMID- 19744930
TI  - Short form glutathione peroxidase 4 is the essential isoform required for
      survival and somatic mitochondrial functions.
AB  - Glutathione peroxidase 4 (Gpx4) is an essential antioxidant enzyme having
      multiple functions. A long form Gpx4 protein and a short form Gpx4 protein, which
      are distinguishable by the presence or lack of a mitochondrial signal peptide at
      the N terminus, are generated from the Gpx4 gene. In this study, we generated
      transgenic mice using mutated GPX4 genes encoding either the long form Gpx4
      (lGPX4 gene) or the short form Gpx4 (sGPX4 gene). Our results showed that
      transgenic mice with the sGPX4 gene had increased Gpx4 protein in all tissues and
      were protected against diquat-induced apoptosis in liver. Moreover, the sGPX4
      gene was able to rescue the lethal phenotype of the mouse Gpx4-null mutation. In
      contrast, transgenic mice with the lGPX4 gene had increased Gpx4 protein only in
      the testes, and the lGPX4 gene failed to rescue the lethal phenotype of the mouse
      Gpx4-null mutation. In Gpx4-null mice rescued by the sGPX4 gene, the Gpx4 protein
      was present in mitochondria isolated from somatic tissues, and the
      submitochondrial distribution pattern of the Gpx4 protein in these mice was
      identical to that in wild-type mice. Interestingly, the male Gpx4-null mice
      rescued by the sGPX4 gene were infertile and exhibited sperm malformation.
      Together, our results demonstrated for the first time that the short form Gpx4
      protein is present in somatic tissue mitochondria and is essential for survival
      and protection against apoptosis in mice, whereas the long form Gpx4 protein is
      important for male fertility.

PMID- 19744931
TI  - Function of histone deacetylase 6 as a cofactor of nuclear receptor coregulator
      LCoR.
AB  - Ligand-dependent corepressor LCoR was identified as a protein that interacts with
      the estrogen receptor alpha (ERalpha) ligand binding domain in a hormone
      dependent manner. LCoR also interacts directly with histone deacetylase 3 (HDAC3)
      and HDAC6. Notably, HDAC6 has emerged as a marker of breast cancer prognosis.
      However, although HDAC3 is nuclear, HDAC6 is cytoplasmic in many cells. We found
      that HDAC6 is partially nuclear in estrogen-responsive MCF7 cells, colocalizes
      with LCoR, represses transactivation of estrogen-inducible reporter genes, and
      augments corepression by LCoR. In contrast, no repression was observed upon HDAC6
      expression in COS7 cells, where it is exclusively cytoplasmic. LCoR binds to
      HDAC6 in vitro via a central domain, and repression by LCoR mutants lacking this
      domain was attenuated. Kinetic chromatin immunoprecipitation assays revealed
      hormone-dependent recruitment of LCoR to promoters of ERalpha-induced target
      genes in synchrony with ERalpha. HDAC6 was also recruited to these promoters, and
      repeat chromatin immunoprecipitation experiments confirmed the corecruitment of
      LCoR with ERalpha and with HDAC6. Remarkably, however, although we find evidence
      for corecruitment of LCoR and ERalpha on genes repressed by the receptor, LCoR
      and HDAC6 failed to coimmunoprecipitate, suggesting that they are part of
      distinct complexes on these genes. Although small interfering RNA-mediated
      knockdown of LCoR or HDAC6 augmented expression of an estrogen-sensitive reporter
      gene in MCF7 cells, unexpectedly their ablation led to reduced expression of some
      endogenous estrogen target genes. Taken together, these data establish that HDAC6
      can function as a cofactor of LCoR but suggest that they may act in enhance
      expressing some target genes.

PMID- 19744932
TI  - Ligand-dependent corepressor LCoR is an attenuator of progesterone-regulated gene
      expression.
AB  - Ligand-dependent corepressor LCoR interacts with the progesterone receptor (PR)
      and estrogen receptor ERalpha in the presence of hormone. LCoR contains tandem N
      terminal PXDLS motifs that recruit C-terminal-binding protein (CtBP) corepressors
      as well as a C-terminal helix-turn-helix (HTH) domain. Here, we analyzed the
      function of these domains in coregulation of PR- and ERalpha-regulated gene
      expression. LCoR and CtBP1 colocalize in nuclear bodies that also contain CtBP
      interacting protein CtIP and polycomb group repressor complex marker BMI1.
      Coexpression of CtBP1 in MCF7 or T47D breast cancer cells augmented corepression
      by LCoR, whereas coexpression of CtIP did not, consistent with direct interaction
      of LCoR with CtBP1, but not CtIP. The N-terminal region containing the PXDLS
      motifs is necessary and sufficient for CTBP1 recruitment and essential for full
      corepression. However, LCoR function was also strongly dependent on the helix
      turn-helix domain, as its deletion completely abolished corepression. LCoR, CtBP,
      and CtIP were recruited to endogenous PR- and ERalpha-stimulated genes in a
      hormone-dependent manner. Similarly, LCoR was recruited to estrogen-repressed
      genes, whereas hormone treatment reduced CtBP1 binding. Small interfering RNA
      mediated knockdown of LCoR or CtBP1 augmented expression of progesterone- and
      estrogen-stimulated reporter genes as well as endogenous progesterone-stimulated
      target genes. In contrast, their ablation had gene-specific effects on ERalpha
      regulated transcription that generally led to reduced gene expression. Taken
      together, these results show that multiple domains contribute to LCoR function.
      They also reveal a role for LCoR and CtBP1 as attenuators of progesterone
      regulated transcription but suggest that LCoR and CtBP1 can act to enhance
      transcription of some genes.

PMID- 19744933
TI  - Bayesian perspectives for epidemiologic research: III. Bias analysis via missing
      data methods.
AB  - I present some extensions of Bayesian methods to situations in which biases are
      of concern. First, a basic misclassification problem is illustrated using data
      from a study of sudden infant death syndrome. Bayesian analyses are then given.
      These analyses can be conducted directly, or by converting actual-data records to
      incomplete records and prior distributions to complete-data records, then
      applying missing-data techniques to the augmented data set. The analyses can
      easily incorporate any complete ('validation' or second-stage) data that might be
      available, as well as adjustments for confounding and selection bias. The
      approach illustrates how conventional analyses depend on implicit certainty that
      bias parameters are null and how these implausible assumptions can be replaced by
      plausible priors for bias parameters.

PMID- 19744934
TI  - The tenacious nature of memory binding for arousing negative items.
AB  - In two experiments, we investigated whether people are better or worse at
      updating memory for the location of emotional pictures than of neutral pictures.
      We measured participants' memories for the locations of both arousing negative
      pictures and neutral pictures while manipulating practice (encountering the same
      event repeatedly) and interference (encountering the same picture in a different
      location). Memory for the context of emotional items was less likely to be
      corrected when erroneous and was less likely to be correctly updated when the
      context changed. These results suggest that initial item-context binding is more
      tenacious for emotional items than for neutral items, even when such binding is
      incorrect.

PMID- 19744935
TI  - Attention during memory retrieval enhances future remembering.
AB  - Memory retrieval is a powerful learning event that influences whether an
      experience will be remembered in the future. Although retrieval can succeed in
      the presence of distraction, dividing attention during retrieval may reduce the
      power of remembering as an encoding event. In the present experiments,
      participants studied pictures of objects under full attention and then engaged in
      item recognition and source memory retrieval under full or divided attention. Two
      days later, a second recognition and source recollection test assessed the impact
      of attention during initial retrieval on long-term retention. On this latter
      test, performance was superior for items that had been tested initially under
      full versus divided attention. More importantly, even when items were correctly
      recognized on the first test, divided attention reduced the likelihood of
      subsequent recognition on the second test. The same held true for source
      recollection. Additionally, foils presented during the first test were also less
      likely to be later recognized if they had been encountered initially under
      divided attention. These findings demonstrate that attentive retrieval is
      critical for learning through remembering.

PMID- 19744936
TI  - Age differences in collaborative memory: the role of retrieval manipulations.
AB  - In two experiments, we examined age differences in collaborative inhibition
      (reduced recall in pairs of people, relative to pooled individuals) across
      repeated retrieval attempts. Younger and older adults studied categorized word
      lists and were then given two consecutive recall tests and a recognition test. On
      the first recall test, the subjects were given free-report cued recall or forced
      report cued recall instructions (Experiment 1) or free recall instructions
      (Experiment 2) and recalled the lists either alone or in collaboration with
      another subject of the same age group. Free-report cued recall and free recall
      instructions warned the subjects not to guess, whereas forced-report cued recall
      instructions required them to guess. Collaborative inhibition was obtained for
      both younger and older adults on initial tests of free-report cued recall, forced
      report cued recall, and free recall, showing that the effect generalizes across
      several tests for both younger and older adults. Collaborative inhibition did not
      persist on subsequent individual recall or recognition tests for list items.
      Older adults consistently falsely recalled and recognized items more than did
      younger adults, as had been found in previous studies. In addition, prior
      collaboration may exaggerate older adults' tendency toward higher false alarms on
      a subsequent recognition test, but only after a free recall test. The results
      provide generality to the phenomenon of collaborative inhibition and can be
      explained by invoking concepts of strategy disruption and source monitoring.

PMID- 19744937
TI  - Strength-based criterion shifts in recognition memory.
AB  - In manipulations of stimulus strength between lists, a more lenient signal
      detection criterion is more frequently applied to a weak than to a strong
      stimulus class. However, with randomly intermixed weak and strong test probes,
      such a criterion shift often does not result. A procedure that has yielded delay
      based within-list criterion shifts was applied to strength manipulations in
      recognition memory for categorized word lists. When participants made semantic
      ratings about each stimulus word, strength-based criterion shifts emerged
      regardless of whether words from pairs of categories were studied in separate
      blocks (Experiment 1) or in intermixed blocks (Experiment 2). In Experiment 3,
      the criterion shift persisted under the semantic-rating study task, but not under
      rote memorization. These findings suggest that continually adjusting the
      recognition decision criterion is cognitively feasible. They provide a technique
      for manipulating the criterion shift, and they identify competing theoretical
      accounts of these effects.

PMID- 19744938
TI  - Doomed to repeat the successes of the past: history is best forgotten for
      repeated choices with nonstationary payoffs.
AB  - Many everyday tasks involve repeated choices in which past outcomes are used to
      estimate payoffs but in which present payoffs may differ from past ones. Two
      experiments with 10 decision problems employing the decisions-from-feedback
      paradigm examined the choice between two risky options, wherein the payoff
      probabilities for one option could change over a sequence of trials. Participants
      either saw the outcomes associated with each option, or additionally were given a
      "history" summarizing the outcomes of previous trials. Participants adapted
      quickly to new problems, but adapted slowly to payoff changes. Providing a
      history improved initial choices, but had a null or negative impact on later ones
      although, appropriately, the summary received less weight in later trials. An
      associative choice model captured changes in preference, but not initial patterns
      of choice. The findings emphasize the adaptive value of forgetting in unstable
      decision environments, but illustrate how providing additional relevant
      information may hinder this.

PMID- 19744939
TI  - The effects of domain knowledge on metacomprehension accuracy.
AB  - In the present research, we examined the relationship between readers' domain
      knowledge and their ability to judge their comprehension of novel domain-related
      material. Participants with varying degrees of baseball knowledge read five texts
      on baseball-related topics and five texts on non-baseball-related topics,
      predicted their performance, and completed tests for each text. Baseball
      knowledge was positively related to absolute accuracy within the baseball domain
      but was unrelated to relative accuracy within the baseball domain. Also, the
      readers showed a general underconfidence bias, but the bias was less extreme for
      higher knowledge readers. The results challenge common assumptions that experts'
      metacognitive judgments are less accurate than novices'. Results involving topic
      familiarity ratings and a no-reading control group suggest that higher knowledge
      readers are not more likely to ignore text-specific cues in favor of a domain
      familiarity heuristic, but they do appear to make more effective use of domain
      familiarity in predicting absolute performance levels.

PMID- 19744940
TI  - Nonlocal effects of prosodic boundaries.
AB  - Placing a prosodic boundary before a phrase may influence its syntactic analysis.
      However, the boundary's effect depends on the presence, size, and position of
      other, earlier, prosodic boundaries. In three experiments, we extend previous
      results about the effect of the position of the early boundary. In sentences in
      which a final phrase may modify either a local verb or an earlier verb, a
      boundary immediately after the first verb leads to more first-verb attachments
      than when the earlier boundary appears in another position between the two verbs
      (Experiments 1 and 2). This effect cannot be attributed to weaker effects of more
      distant boundaries (Experiment 2), but is likely due to the first verb being more
      prominent when a boundary immediately follows it, since similar effects are
      observed when the verb is accented (Experiment 3). The results support the
      informative boundary hypothesis and show that the impact of earlier, nonlocal
      boundaries is not fully uniform.

PMID- 19744941
TI  - Dynamics of activation of semantically similar concepts during spoken word
      recognition.
AB  - Semantic similarity effects provide critical insight into the organization of
      semantic knowledge and the nature of semantic processing. In the present study,
      we examined the dynamics of semantic similarity effects by using the visual world
      eyetracking paradigm. Four objects were shown on a computer monitor, and
      participants were instructed to click on a named object, during which time their
      gaze position was recorded. The likelihood of fixating competitor objects was
      predicted by the degree of semantic similarity to the target concept. We found
      reliable, graded competition that depended on degree of target-competitor
      similarity, even for distantly related items for which priming has not been found
      in previous priming studies. Time course measures revealed a consistently earlier
      fixation peak for near semantic neighbors relative to targets. Computational
      investigations with an attractor dynamical model, a spreading activation model,
      and a decision model revealed that a combination of excitatory and inhibitory
      mechanisms is required to obtain such peak timing, providing new constraints on
      models of semantic processing.

PMID- 19744942
TI  - Verbal representation in task order control: an examination with transition and
      task cues in random task switching.
AB  - Recent task-switching studies in which a predictable task sequence has been used
      have indicated that verbal representation contributes to the control of task
      order information. The present study focused on the role of verbal representation
      in sequential task decisions, which are an important part of task order control,
      and examined the effects of articulatory suppression in a random-task-cuing
      paradigm with two different types of cues presented just before the presentation
      of a stimulus: a transition cue and a task cue. The former cue provided
      information only about switching or repeating the task, whereas the latter was
      associated directly with the identity of the task (i.e., indicating a parity or a
      magnitude task). In Experiment 1, in which transition cues guided task sequences,
      articulatory suppression impaired performance in both repetition and switch
      trials, thereby increasing the mixing costs. In Experiment 2, in which a task
      cue, rather than a transition cue, was presented to examine the influence of a
      cue-decoding process, articulatory suppression had no specific effect on task
      performance. Experiment 3, in which the transition cue and the task cue were
      randomly presented in the same block to equalize the memory load and task
      strategy for the two types of cues, confirmed that articulatory suppression
      significantly increased the mixing costs only in transition cue trials. The
      results from the three experiments indicated that the use of verbal
      representation is effective in sequential task decision-that is, in selecting a
      task set on the basis of transient task order information in both repetition and
      switch trials.

PMID- 19744943
TI  - The time course of task switching: a speed--accuracy trade-off analysis.
AB  - On each trial of this study, participants either switched between or repeated two
      simple, two-choice tasks involving either letter or digit classifications. Speed
      accuracy trade-off (SAT) curves were obtained using the response-signal method of
      eliciting speeded responses at various response time lags after the presentation
      of the stimulus for the second task. The key finding from separate analyses of
      the three SAT-curve parameters (intercept, rate, and asymptote) was that the
      location of the intercept of the SAT function (i.e., the point at which
      responding rises above chance) was shifted upward for both short and long
      response-stimulus intervals under task-switch conditions but only when the
      responses associated with each of the letter-digit stimulus components were
      incompatible.

PMID- 19744944
TI  - The effectiveness of hysteroscopy in improving pregnancy rates in subfertile
      women without other gynaecological symptoms: a systematic review.
AB  - BACKGROUND: Although hysteroscopy is frequently used in the management of
      subfertile women, a systematic review of the evidence on this subject is lacking.
      METHODS: We summarized and appraised the evidence for the benefit yielded by this
      procedure. Our systematic search was limited to randomized and controlled
      studies. The QUOROM and MOOSE guidelines were followed. Language restrictions
      were not applied. RESULTS: We identified 30 relevant publications. Hysteroscopic
      removal of endometrial polyps with a mean diameter of 16 mm detected by
      ultrasound doubles the pregnancy rate when compared with diagnostic hysteroscopy
      and polyp biopsy in patients undergoing intrauterine insemination, starting 3
      months after the surgical intervention [relative risk (RR) = 2.3; 95% confidence
      interval (CI): 1.6-3.2]. In patients with one fibroid structure smaller than 4
      cm, there was a marginally significant benefit from myomectomy when compared with
      expectant management (RR = 1.9; 95% CI: 1.0-3.7). Hysteroscopic metroplasty for
      septate uterus resulted in fewer pregnancies in patients with subfertility when
      compared with those with recurrent pregnancy loss (RR = 0.7; 95% CI: 0.5-0.9).
      Randomized controlled studies on hysteroscopic treatment of intrauterine
      adhesions are lacking. Hysteroscopy in the cycle preceding a subsequent IVF
      attempt nearly doubles the pregnancy rate in patients with at least two failed
      IVF attempts compared with starting IVF immediately (RR = 1.7; 95% CI: 1.5-2.0).
      CONCLUSIONS: Scarce evidence on the effectiveness of hysteroscopic surgery in
      subfertile women with polyps, fibroids, septate uterus or intrauterine adhesions
      indicates a potential benefit. More randomized controlled trials are needed
      before widespread use of hysteroscopic surgery in the general subfertile
      population can be justified.

PMID- 19744945
TI  - Understanding the current population survey's insurance estimates and the
      Medicaid 'undercount'.
AB  - The widely cited Census Bureau estimates of the number of uninsured people, based
      on the Current Population Survey, probably overstate the number of uninsured
      people. This is because of a Medicaid "undercount": Fewer people report to survey
      takers that they're covered by Medicaid than program administrative data show are
      enrolled. Our study finds that the undercount can be explained by the inability
      of people to recall their insurance status accurately from the previous year. We
      suggest that other data sources, such as Census's American Community Survey,
      should be studied to determine whether they would provide better estimates of the
      uninsured.

PMID- 19744946
TI  - Exercise training decreases store-operated Ca2+entry associated with metabolic
      syndrome and coronary atherosclerosis.
AB  - AIMS: Stenting attenuates restenosis, but accelerated coronary artery disease
      (CAD) adjacent to the stent (peri-stent CAD) remains a concern in metabolic
      syndrome (MetS). Smooth muscle cell proliferation, a major mechanism of CAD, is
      mediated partly by myoplasmic Ca2+ dysregulation and store-operated Ca2+ entry
      (SOCE) via canonical transient receptor potential 1 (TRPC1) channels is proposed
      to play a key role. Exercise is known to prevent Ca2+ dysregulation in CAD. We
      tested the hypothesis that MetS increases SOCE and peri-stent CAD and exercise
      attenuates these events. METHODS AND RESULTS: Groups (n = 9 pigs each) were (i)
      healthy lean Ossabaw swine fed standard chow, (ii) excess calorie atherogenic
      diet fed (MetS), and (iii) aerobically exercise trained starting after 50 weeks
      of development of MetS (XMetS). Bare metal stents were placed after 54 weeks on
      diets, and CAD and SOCE were assessed 4 weeks later. Coronary cells were
      dispersed proximal to the stent (peri-stent) and from non-stent segments, and
      fura-2 fluorescence was used to assess SOCE, which was verified by Ni2+ blockade
      and insensitivity to nifedipine. XMetS pigs had increased physical work capacity
      and decreased LDL/HDL (P < 0.05), but no attenuation of robust insulin
      resistance, glucose intolerance, hypertriglyceridaemia, or hypertension. CAD was
      greater in peri-stented vs. non-stented artery segments. MetS had the greatest
      CAD, SOCE, and TRPC1 and STIM1 mRNA and protein expression, which were all
      attenuated in XMetS. CONCLUSION: This is the first report of the protective
      effect of exercise on native CAD, peri-stent CAD, SOCE, and molecular expression
      of TRPC1, STIM1, and Orai1 in MetS.

PMID- 19744947
TI  - Proteasome inhibition during myocardial infarction.
AB  - The ubiquitin-proteasome system (UPS) plays a central role in protein degradation
      and regulates a variety of critical cellular processes. During recent years, the
      cardiac UPS has become increasingly recognized as a key regulator of cardiac
      function under both physiological and pathological conditions. Numerous studies
      have demonstrated that altered UPS function is involved in the pathogenesis of
      cardiac disease including myocardial ischaemia or infarction. The expression and
      activity of the E3 ubiquitin ligases, which confer substrate specificity in the
      UPS pathway, affect the apoptosis and severity of disease in myocardial ischaemia
      and reperfusion. Although impaired proteasome function is commonly associated
      with myocardial ischaemic injury, recent evidence also supports a
      cardioprotective role for proteasome inhibitors in myocardial ischaemia. We will
      review these studies and data, discuss controversies regarding the UPS
      alterations and use of proteasome inhibitors in myocardial ischaemia, and attempt
      to identify strategies that may enhance their clinical application.

PMID- 19744948
TI  - Ascorbic acid and tetrahydrobiopterin: looking beyond nitric oxide
      bioavailability.

PMID- 19744954
TI  - Salivary cortisol responses to mental stress are associated with coronary artery
      calcification in healthy men and women.
AB  - AIMS: Psychosocial stress is a risk factor for coronary heart disease (CHD),
      although the mechanisms are incompletely understood. We examined the cross
      sectional association between the cortisol response to laboratory-induced mental
      stress and a marker of sub-clinical coronary atherosclerosis. METHODS AND
      RESULTS: Participants were 514 healthy men and women (mean age = 62.9 +/- 5.7
      years), without history or objective signs of CHD, drawn from the Whitehall II
      epidemiological cohort. Salivary cortisol was measured in response to mental
      stressors, consisting of a 5 min Stroop task and a 5 min mirror tracing task.
      Coronary artery calcification (CAC) was measured using electron beam computed
      tomography. Approximately 40% of the sample responded to the stress tasks with a
      notable (>or=1 nmol/L) increase in cortisol. Significant CAC (Agatston score >or=
      100) was recorded in 23.9% of the sample. The cortisol response group
      demonstrated a higher risk of significant CAC (odds ratio = 2.20, 95% CI, 1.39
      3.47) after adjustments for age, gender, baseline cortisol, employment grade, and
      conventional risk factors, although cortisol was unrelated to the presence of
      detectable CAC. Among participants with detectable CAC, the cortisol response
      group also demonstrated higher log Agatston scores compared with non-responders
      (age and sex adjusted scores; 4.51 +/- 0.15 vs. 3.94 +/- 0.13, P = 0.004).
      CONCLUSION: In healthy, older participants without history or objective signs of
      CHD, heightened cortisol reactivity is associated with a greater extent of CAC.
      These data support the notion that heightened hypothalamic pituitary adrenal
      activity is a risk factor for CHD.

PMID- 19744955
TI  - Rethinking the reasons to treat atrial fibrillation? The role of dronedarone in
      reducing cardiovascular hospitalizations.

PMID- 19744956
TI  - Missense mutations in the SH3TC2 protein causing Charcot-Marie-Tooth disease type
      4C affect its localization in the plasma membrane and endocytic pathway.
AB  - Mutations in SH3TC2 (KIAA1985) cause Charcot-Marie-Tooth disease (CMT) type 4C, a
      demyelinating inherited neuropathy characterized by early-onset and scoliosis.
      Here we demonstrate that the SH3TC2 protein is present in several components of
      the endocytic pathway including early endosomes, late endosomes and clathrin
      coated vesicles close to the trans-Golgi network and in the plasma membrane.
      Myristoylation of SH3TC2 in glycine 2 is necessary but not sufficient for the
      proper location of the protein in the cell membranes. In addition to
      myristoylation, correct anchoring also needs the presence of SH3 and TPR domains.
      Mutations that cause a stop codon and produce premature truncations that remove
      most of the TPR domains are expressed as the wild-type protein. In contrast,
      missense mutations in or around the region of the first-TPR domain are absent
      from early endosomes, reduced in plasma membrane and late endosomes and are
      variably present in clathrin-coated vesicles. Our findings suggest that the
      endocytic and membrane trafficking pathway is involved in the pathogenesis of
      CMT4C disease. We postulate that missense mutations of SH3TC2 could impair
      communication between the Schwann cell and the axon causing an abnormal myelin
      formation.

PMID- 19744957
TI  - AIRE activated tissue specific genes have histone modifications associated with
      inactive chromatin.
AB  - The Autoimmune Regulator (AIRE) protein is expressed in thymic medullary
      epithelial cells, where it promotes the ectopic expression of tissue-restricted
      antigens needed for efficient negative selection of developing thymocytes.
      Mutations in AIRE cause APECED syndrome, which is characterized by a breakdown of
      self-tolerance. The molecular mechanism by which AIRE increases the expression of
      a variety of different genes remains unknown. Here, we studied AIRE-regulated
      genes using whole genome expression analysis and chromatin immunoprecipitation.
      We show that AIRE preferentially activates genes that are tissue-specific and
      characterized by low levels of initial expression in stably transfected HEK293
      cell model and mouse thymic medullary epithelial cells. In addition, the AIRE
      regulated genes lack active chromatin marks, such as histone H3 trimethylation
      (H3K4me3) and acetylation (AcH3), on their promoters. We also show that during
      activation by AIRE, the target genes acquire histone H3 modifications associated
      with transcription and RNA polymerase II. In conclusion, our data show that AIRE
      is able to promote ectopic gene expression from chromatin associated with histone
      modifications characteristic to inactive genes.

PMID- 19744958
TI  - Myosin VI is required for the proper maturation and function of inner hair cell
      ribbon synapses.
AB  - The ribbon synapses of auditory inner hair cells (IHCs) undergo morphological and
      electrophysiological transitions during cochlear development. Here we report that
      myosin VI (Myo6), an actin-based motor protein involved in genetic forms of
      deafness, is necessary for some of these changes to occur. By using post
      embedding immunogold electron microscopy, we showed that Myo6 is present at the
      IHC synaptic active zone. In Snell's waltzer mutant mice, which lack Myo6, IHC
      ionic currents and ribbon synapse maturation proceeded normally until at least
      post-natal day 6. In adult mutant mice, however, the IHCs displayed immature
      potassium currents and still fired action potentials, as normally only observed
      in immature IHCs. In addition, the number of ribbons per IHC was reduced by 30%,
      and 30% of the remaining ribbons were morphologically immature. Ca2+-dependent
      exocytosis probed by capacitance measurement was markedly reduced despite normal
      Ca2+ currents and the large proportion of morphologically mature synapses, which
      suggests additional defects, such as loose Ca2+-exocytosis coupling or
      inefficient vesicular supply. Finally, we provide evidence that Myo6 and
      otoferlin, a putative Ca2+ sensor of synaptic exocytosis also involved in a
      genetic form of deafness, interact at the IHC ribbon synapse, and we suggest that
      this interaction is involved in the recycling of synaptic vesicles. Our findings
      thus uncover essential roles for Myo6 at the IHC ribbon synapse, in addition to
      that proposed in membrane turnover and anchoring at the apical surface of the
      hair cells.

PMID- 19744959
TI  - Pharmacological activation of PPARbeta/delta stimulates utrophin A expression in
      skeletal muscle fibers and restores sarcolemmal integrity in mature mdx mice.
AB  - A therapeutic strategy to treat Duchenne muscular dystrophy (DMD) involves
      identifying compounds that can elevate utrophin A expression in muscle fibers of
      affected patients. The dystrophin homologue utrophin A can functionally
      substitute for dystrophin when its levels are enhanced in the mdx mouse model of
      DMD. Utrophin A expression in skeletal muscle is regulated by mechanisms that
      promote the slow myofiber program. Since activation of peroxisome proliferator
      activated receptor (PPAR) beta/delta promotes the slow oxidative phenotype in
      skeletal muscle, we initiated studies to determine whether pharmacological
      activation of PPARbeta/delta provides functional benefits to the mdx mouse.
      GW501516, a PPARbeta/delta agonist, was found to stimulate utrophin A mRNA levels
      in C2C12 muscle cells through an element in the utrophin A promoter. Expression
      of PPARbeta/delta was greater in skeletal muscles of mdx versus wild-type mice.
      We treated 5-7-week-old mdx mice with GW501516 for 4 weeks. This treatment
      increased the percentage of muscle fibers expressing slower myosin heavy chain
      isoforms and stimulated utrophin A mRNA levels leading to its increased
      expression at the sarcolemma. Expression of alpha1-syntrophin and beta
      dystroglycan was restored to the sarcolemma. Improvement of mdx sarcolemmal
      integrity was evidenced by decreased intracellular IgM staining and decreased in
      vivo Evans blue dye (EBD) uptake. GW501516 treatment also conferred protection
      against eccentric contraction (ECC)-induced damage of mdx skeletal muscles, as
      shown by a decreased contraction-induced force drop and reduction of dye uptake
      during ECC. These results demonstrate that pharmacological activation of
      PPARbeta/delta might provide functional benefits to DMD patients through
      enhancement of utrophin A expression.

PMID- 19744960
TI  - GIGYF2 gene disruption in mice results in neurodegeneration and altered insulin
      like growth factor signaling.
AB  - Grb10-Interacting GYF Protein 2 (GIGYF2) was initially identified through its
      interaction with Grb10, an adapter protein that binds activated IGF-I and insulin
      receptors. The GIGYF2 gene maps to human chromosome 2q37 within a region linked
      to familial Parkinson's disease (PARK11 locus), and association of GIGYF2
      mutations with Parkinson's disease has been described in some but not other
      recent publications. This study investigated the consequences of Gigyf2 gene
      disruption in mice. Gigyf2 null mice undergo apparently normal embryonic
      development, but fail to feed and die within the first 2 post-natal days.
      Heterozygous Gigyf2(+/-) mice survive to adulthood with no evident metabolic or
      growth defects. At 12-15 months of age, the Gigyf2(+/-) mice begin to exhibit
      motor dysfunction manifested as decreased balance time on a rotating horizontal
      rod. This is associated with histopathological evidence of neurodegeneration and
      rare intracytoplasmic Lewy body-like inclusions in spinal anterior horn motor
      neurons. There are alpha-synuclein positive neuritic plaques in the brainstem and
      cerebellum, but no abnormalities in the substantia nigra. Primary cultured embryo
      fibroblasts from Gigyf2 null mice exhibit decreased IGF-I-stimulated IGF-I
      receptor tyrosine phosphorylation and augmented ERK1/2 phosphorylation. These
      data provide further evidence for an important role of GIGYF2 in age-related
      neurodegeneration and IGF pathway signaling.

PMID- 19744961
TI  - Genome-wide significant predictors of metabolites in the one-carbon metabolism
      pathway.
AB  - Low plasma B-vitamin levels and elevated homocysteine have been associated with
      cancer, cardiovascular disease and neurodegenerative disorders. Common variants
      in FUT2 on chromosome 19q13 were associated with plasma vitamin B12 levels among
      women in a genome-wide association study in the Nurses' Health Study (NHS) NCI
      Cancer Genetic Markers of Susceptibility (CGEMS) project. To identify additional
      loci associated with plasma vitamin B12, homocysteine, folate and vitamin B6
      (active form pyridoxal 5'-phosphate, PLP), we conducted a meta-analysis of three
      GWA scans (total n = 4763, consisting of 1658 women in NHS-CGEMS, 1647 women in
      Framingham-SNP-Health Association Resource (SHARe) and 1458 men in SHARe). On
      chromosome 19q13, we confirm the association of plasma vitamin B12 with rs602662
      and rs492602 (P-value = 1.83 x 10(-15) and 1.30 x 10(-14), respectively) in
      strong linkage disequilibrium (LD) with rs601338 (P = 6.92 x 10(-15)), the FUT2
      W143X nonsense mutation. We identified additional genome-wide significant loci
      for plasma vitamin B12 on chromosomes 6p21 (P = 4.05 x 10(-08)), 10p12 (P
      value=2.87 x 10(-9)) and 11q11 (P-value=2.25 x 10(-10)) in genes with biological
      relevance. We confirm the association of the well-studied functional candidate
      SNP 5,10-methylene tetrahydrofolate reductase (MTHFR) Ala222Val (dbSNP ID:
      rs1801133; P-value=1.27 x 10(-8)), on chromosome 1p36 with plasma homocysteine
      and identify an additional genome-wide significant locus on chromosome 9q22 (P
      value=2.06 x 10(-8)) associated with plasma homocysteine. We also identified
      genome-wide associations with variants on chromosome 1p36 with plasma PLP (P
      value=1.40 x 10(-15)). Genome-wide significant loci were not identified for
      plasma folate. These data reveal new biological candidates and confirm prior
      candidate genes for plasma homocysteine, plasma vitamin B12 and plasma PLP.

PMID- 19744962
TI  - X11beta rescues memory and long-term potentiation deficits in Alzheimer's disease
      APPswe Tg2576 mice.
AB  - Increased production and deposition of amyloid beta-protein (Abeta) are believed
      to be key pathogenic events in Alzheimer's disease. As such, routes for lowering
      cerebral Abeta levels represent potential therapeutic targets for Alzheimer's
      disease. X11beta is a neuronal adaptor protein that binds to the intracellular
      domain of the amyloid precursor protein (APP). Overexpression of X11beta inhibits
      Abeta production in a number of experimental systems. However, whether these
      changes to APP processing and Abeta production induced by X11beta overexpression
      also induce beneficial effects to memory and synaptic plasticity are not known.
      We report here that X11beta-mediated reduction in cerebral Abeta is associated
      with normalization of both cognition and in vivo long-term potentiation in aged
      APPswe Tg2576 transgenic mice that model the amyloid pathology of Alzheimer's
      disease. Overexpression of X11beta itself has no detectable adverse effects upon
      mouse behaviour. These findings support the notion that modulation of X11beta
      function represents a therapeutic target for Abeta-mediated neuronal dysfunction
      in Alzheimer's disease.

PMID- 19744963
TI  - Efficacy and safety of pallidal stimulation in primary dystonia: results of the
      Spanish multicentric study.
AB  - BACKGROUND: Dystonia is a complex clinical syndrome originated by a wide range of
      aetiologies. The diagnosis of dystonia is made after the evaluation of
      aetiological, phenomenological and genetic factors. Medications, except in
      patients with dopa-responsive dystonia, are of limited efficacy. Botulinum toxin
      injections are not applicable to patients with generalised dystonia, since many
      muscular groups contribute to disability. Clinical studies in children and adults
      with primary generalised dystonia (PGD) have reported beneficial effects of
      bilateral GPi deep brain stimulation (DBS) in both motor symptoms and disability
      produced by dystonia as well as a favourable impact of DBS in the health-related
      quality of life (HRQoL). Some clinical aspects of GPi stimulation in primary
      dystonia still remain controversial such as the influence of disease duration or
      age at onset in determining the postoperative clinical outcome. RESULTS: The
      authors report the results of a multicentric study designed to assess the
      tolerability and clinical effects of bilateral pallidal DBS on motor impairment,
      functional disability, quality of life, pain and mood in patients with medically
      refractory primary generalised or segmental dystonia.

PMID- 19744964
TI  - Brain atrophy and lesion load measures over 1 year relate to clinical status
      after 6 years in patients with clinically isolated syndromes.
AB  - BACKGROUND: Conventional MRI lesion measures modestly predict long term
      disability in some clinically isolated syndrome (CIS) studies. Brain atrophy
      suggests neuroaxonal loss in multiple sclerosis (MS) with the potential to
      reflect disease progression to a greater extent than lesion measures. OBJECTIVE:
      To investigate whether brain atrophy and lesion load, during the first year in
      patients presenting with CIS, independently predict clinical outcome (development
      of MS and disability at 6 years). METHODS: 99 patients presenting with CIS were
      included in the study. T1 gadolinium enhanced and T2 weighted brain MRI was
      acquired at baseline and approximately 1 year later. Percentage brain atrophy
      rate between baseline and follow-up scans was analysed using SIENA. RESULTS: Mean
      annual brain atrophy rates were -0.38% for all patients, -0.50% in patients who
      had developed MS at 6 years and -0.26% in those who had not. Brain atrophy rate
      (p = 0.005) and baseline T2 lesion load (p<0.001) were independent predictors of
      clinically definite MS. While brain atrophy rate was a predictor of Expanded
      Disability Status Scale (EDSS) score in a univariate analysis, only 1 year T2
      lesion load change (p = 0.007) and baseline gadolinium enhancing lesion number (p
      = 0.03) were independent predictors of EDSS score at the 6 year follow-up. T1
      lesion load was the only MRI parameter which predicted Multiple Sclerosis
      Functional Composite score at the 6 year follow-up. CONCLUSIONS: The findings
      confirm that brain atrophy occurs during the earliest phases of MS and suggest
      that 1 year longitudinal measures of MRI change, if considered together with
      baseline MRI variables, might help to predict clinical status 6 years after the
      first demyelinating event in CIS patients, better than measurements such as
      lesion or brain volumes on baseline MRI alone.

PMID- 19744965
TI  - Adherence to patient selection criteria in patients undergoing transcatheter
      aortic valve implantation with the 18F CoreValve ReValving System.
AB  - BACKGROUND: Anecdotal evidence suggests that transcatheter aortic valve
      implantation (TAVI) is being used beyond pre-market label indications. METHODS:
      To assess the frequency and outcomes associated with "off-label" use of TAVI, we
      conducted a retrospective study, examining adherence to patient selection
      criteria in 63 patients undergoing implantation with the 18F CoreValve ReValving
      System (CRS). Label status (on-label vs off-label) was determined by following
      (1) inclusion/exclusion criteria indicated in the 18F CRS safety and efficacy
      trial and (2) a patient selection matrix indicating anatomical boundaries to
      guide patient selection. Off-label use was defined as the presence of at least
      one exclusion criterion or "non-acceptable" criteria based on the patient
      selection matrix. RESULTS: Off-label implantation was identified in 42 patients
      (67%)-40% had one, 19% had two and 8% had three or more off-label criteria.
      Baseline demographics were similar between the groups except for a higher
      logistic EuroSCORE in the on-label group (19.8 (11.2) vs 14.5 (7.3), p = 0.029).
      There was no significant difference in the procedural success rates between the
      on-label and off-label groups (91% vs 95%, respectively, p = 0.47). The frequency
      of angiographic moderate-severe aortic regurgitation, post-implant dilatation or
      implantation of a second valve was also similar between the groups. At 30 days,
      the cumulative death rate was 10%; there were four deaths in the "on-label" and
      three deaths in the "off-label" group. CONCLUSION: In this study we found that
      "off-label" implantation of the CRS was common. Further studies are needed to
      evaluate the consequences of "label status" for patients undergoing TAVI.

PMID- 19744966
TI  - Balloon expandable stent implantation for native and recurrent coarctation of the
      aorta--prospective computed tomography assessment of stent integrity, aneurysm
      formation and stenosis relief.
AB  - BACKGROUND: Stenting for aortic coarctation is known to be effective in the
      medium term. Aneurysm formation following stent implantation is a recognised
      complication. However, data regarding aortic wall injury and stent integrity
      following stent placement are sparse. OBJECTIVES: We report comprehensive
      clinical, echocardiographic and prospective CT follow-up data following stenting
      for aortic coarctation from a single centre. Methods Full data analysis of all
      patients undergoing balloon expandable stent implantation and follow-up
      procedures in a single tertiary congenital cardiac unit. RESULTS: Between October
      2002 and April 2008, we performed 102 coarctation stent procedures on 88
      patients. Median age was 20.6 years (range 8.5-65) and median weight 65 kg (range
      34-101). 94 stents (26 covered) were implanted. 12 procedures were re
      dilatations. Stenting resulted in a reduction of the gradient across the site of
      coarctation, from a median of 20 mm Hg to 4 mm Hg. There were no procedure
      related deaths. Four patients had immediate complications (one requiring
      emergency surgery). During median follow-up of 34.5 months (range 4.2-72.8), two
      patients had late complications requiring additional stent procedures. Follow-up
      CT data are available in 84 patients with MRI in one patient (96.5%). Only one
      patient developed a procedure-related aortic aneurysm. All stent fractures (n=7)
      occurred with a single stent design. CONCLUSIONS: Stenting for aortic coarctation
      and re-coarctation is effective with low immediate complication rates. CT is
      useful in the longer term for assessment of stent integrity and post-procedural
      aneurysm formation. Overall incidence of post-procedural aneurysm is rare and
      stent fractures were not seen with newer generation stents.

PMID- 19744967
TI  - Out-of-hospital cardiac arrest in South Asian and white populations in London:
      database evaluation of characteristics and outcome.
AB  - OBJECTIVE: To compare out-of-hospital cardiac arrest (OOHCA) characteristics in
      white and South Asian populations within Greater London. METHODS: Data for OOHCAs
      were extracted from 1 April 2003 to 31 March 2007. Primary study variables
      included age, gender, ethnicity, response times from 999 call to ambulance
      arrival, initial cardiac rhythm, whether bystander cardiopulmonary resuscitation
      was provided before arrival of the London Ambulance Service (LAS) NHS Trust crew,
      whether the arrest was witnessed (bystander or LAS crew) and hospital outcome,
      including survival to hospital admission and discharge. RESULTS: Of 13 013 OOHCAs
      of presumed cardiac cause, 3161 (24.3%) had ethnicity codes assigned. These
      comprised 63.1% (n = 1995) white and 5.8% (n = 183) South Asian people, with the
      remainder from other backgrounds. White patients were on average 5 years older
      than South Asians (69.5 vs 64.6, p<0.005). Response time (7.48 min vs 7.46 min),
      bystander cardiopulmonary resuscitation (34.4% vs 29.7%), initial cardiac rhythm
      (29.5% vs 30.4%) and survival to admission (22.2% vs 22.5%) and discharge (8.7%
      vs 8.9%) were comparable between the two ethnic groups. South Asians were
      slightly more likely to have a witnessed an OOHCA than their white counterparts
      (OR = 1.1, 95% CI 1.0 to 1.2). DISCUSSION: The quality of care provided was
      comparable between white and South Asian populations. The data support the
      emerging view that South Asians' high mortality from coronary heart disease
      reflects higher incidence rather than higher case fatality. South Asians had an
      OOHCA at a significantly younger age. The study demonstrates the importance of
      ethnic coding within the emergency services.

PMID- 19744968
TI  - Endometriosis: science and sense.

PMID- 19744969
TI  - Reassessing the evidence for the link between dioxin and endometriosis: from
      molecular biology to clinical epidemiology.
AB  - A 1993 study reporting the link between exposure to dioxin and the risk of
      developing endometriosis in rhesus monkeys prompted many investigators to look
      suspiciously at dioxin. Since 1993, many in vitro, animal and epidemiological
      studies have been published, but the link between dioxin exposure and
      endometriosis is still unclear. The aim of our review is to present a summary of
      the biological effects of dioxin and its aryl hydrocarbon receptor, and to
      reassess the evidence presented in published, in vitro, preclinical and
      epidemiological studies regarding the association between dioxins and
      endometriosis. Although in vitro and animal studies provide results in support
      for a role of dioxins in the pathogenesis of endometriosis, caution should be
      exercised since these findings are mostly context dependent and since negative
      findings from these studies are rarely published. On the basis of our review of
      original epidemiological studies, no significant evidence can be found to support
      a link between dioxins and endometriosis in women. This observation can be
      explained by positive publication bias and by significant methodological problems
      associated with these studies, or by the absence of such a link. In conclusion,
      it seems that there is insufficient evidence at this moment in support of the
      hypothesis that dioxin exposure may lead to increased risk of developing
      endometriosis in women.

PMID- 19744970
TI  - Comparison of arterial and capillary blood gas values in poisoning department
      assessment.
AB  - The aim of this study was to compare simultaneously obtained arterial and
      capillary blood gas (CBG) values in comatose-poisoned patients presented with
      stable vital signs. Forty-five adult patients with a diagnosis of coma because of
      poisoning and stable vital signs were included in this prospective study. With
      respect to pH, the arterial blood gas (ABG) and CBG values correlated
      satisfactorily (r(2) = .91) and had an acceptable limit of agreements (LOAs; 
      0.04 to 0.06). With respect to base excess (BE), the ABG and CBG values
      correlated well (r(2) = .85), but their 95% LOAs seem too wide to allow
      substitution (-4.4 to 2.7). PCO(2) (r(2) = .61), HCO(3) (r(2) = .71) and PO(2)
      (r(2) = .53) correlated less reliably. A capillary PCO(2) of 51.7 mm Hg had a
      sensitivity of 100% and a specificity of 95.12% for detecting hypercarbia (area
      under the curve, 0.99; 95% Confidence Interval, 0.90-0.99; p < .0001). In
      conclusion, CBG analysis for pH may be a reliable substitute for ABG analysis in
      the initial evaluation of patients presenting with coma and stable vital signs to
      the poisoning emergency department (PED). Subsequent ABG may be required in
      patients with capillary PCO(2) > 51.7 mm Hg.

PMID- 19744971
TI  - Effects of exposure to pesticides during pregnancy on placental maturity and
      weight of newborns: a cross-sectional pilot study in women from the Chihuahua
      State, Mexico.
AB  - It is known that pesticides cross the placental barrier and can cause alterations
      in the development of placental structures resulting in adverse effects in
      reproduction. The objectives of this study were to investigate the effects of
      pesticide exposure during pregnancy on placental maturity and to evaluate the
      relationship between placental maturity, gestational age and birth weight. We
      collected the placentas from singleton pregnancies from women exposed (n = 9) and
      non-exposed (n = 45 full-term and n = 31 preterm) to pesticides as evaluated
      geographically, by questionnaire and by acetylcholinesterase levels. Placental
      morphometry from the central and peripheral regions was examined by microscopy
      and staining with hematoxylin and eosin. The placental maturity index (PMI) was
      estimated by dividing the number of epithelial plates in terminal villi to their
      thickness in 1 mm(2) of the placental parenchyma. Gestational age, birth weight
      and the following characteristics of the mother were also recorded: pre-pregnancy
      body mass index, weight gain during pregnancy and hemoglobin concentrations.
      Birth weight and the gestational age were correlated with PMI (r = .54 and r =
      .44, respectively; p < .01). Pesticide exposure was associated with a higher PMI
      (beta = 7.38, p = .01) after adjusting by variables related to placental
      maturity. In conclusion, the results suggest a relationship between prenatal
      exposure to pesticides and placental maturity and may potentially affect the
      nutrient transport from the mother to the fetus.

PMID- 19744972
TI  - Oxidative stress induced by morphine in brain of rats fed with a protein
      deficient diet.
AB  - The objective of the study is to determine the damage by oxidative stress induced
      by morphine in brain of rats fed with a protein-deficient diet. Twenty-eight
      malnourished male Wistar rats, 30 days old, were used in the study. The animals
      were divided into four groups of 7 rats per group. Group I received NaCl and the
      groups II; III and IV intraperitoneally received 3, 6 and 12 mg/kg of morphine
      sulphate, respectively, in a single dose. Animals were sacrificed and the levels
      of glutathione (GSH), dopamine, tryptophan and 5-hydroxyindole-3-acetic acid (5
      HIAA) as well as, Na(+)/K(+) ATPase and total ATPase activity in the brain were
      measured. Tryptophan levels and Na(+)/K( +) ATPase activity showed non
      significant changes in the experimental group. Levels of 5-HIAA decreased
      significantly (p = .03) in animals that received 12 mg/kg of morphine and in
      animals that received 3 mg/kg, levels of GSH and dopamine were found to have a
      significant decrease (p < .05), but a significant increase in the group that
      received 12 mg/kg of morphine (p < .05). Total ATPase activity increased
      significantly in the groups that received 3 mg/kg (p = .015) and 6 mg/kg (p =
      .0001) of morphine. The results show that malnutrition induces changes in
      cellular regulation and biochemical responses to oxidative stress caused by
      morphine sulphate.

PMID- 19744973
TI  - Hydraulic properties of naturally regenerated beech saplings respond to canopy
      opening.
AB  - Enhanced sapling growth in advance regeneration requires gaps in the canopy, but
      is often delayed after canopy opening, because acclimation of saplings to the new
      environment is gradual and may last for several years. Canopy opening is expected
      to result in an increased transpiration because of a larger climatic demand and a
      higher stomatal conductance linked to the higher rates of photosynthesis.
      Therefore, we focused on the changes in water relations and the hydraulic
      properties of beech (Fagus sylvatica L.) saplings during 2 years after canopy
      opening. We tested the hypothesis that an increase in leaf-specific hydraulic
      conductance and a decrease in vulnerability to cavitation occur to sustain an
      enhanced transpiration. Hydraulic conductance of defoliated shoots, vulnerability
      to cavitation, size and density of xylem vessels as well as stomatal conductance
      were recorded on saplings growing in shade (S saplings) or in gaps created by
      opening the canopy (shade-to-light, SL saplings). Hydraulic conductance per unit
      cross-sectional area (K(AS)) did not differ in the shoots of S and SL saplings.
      But a higher ratio stem cross-sectional area/leaf area resulted in a higher leaf
      specific hydraulic conductance of the shoots (K(AL)) of SL saplings. Contrary to
      expectations, vulnerability to cavitation increased transitorily in stems during
      the first year after canopy opening and no difference was observed between the
      two treatments in light-saturated stomatal conductance. During the second year,
      vulnerability to cavitation was similar in the S and SL saplings and light
      saturated stomatal conductance increased in SL saplings. These results
      demonstrate a release of the hydraulic constraints after canopy opening with an
      adjustment of the ratio stem cross-sectional area/leaf area. But the larger
      vulnerability to cavitation during the first year could limit stomatal opening
      and therefore the ability of beech saplings to use the available light for
      photosynthesis and could therefore partly explain why the growth increase was
      delayed to the second growing season after canopy opening.

PMID- 19744974
TI  - Comparisons between geographies of mortality and deprivation from the 1900s and
      2001: spatial analysis of census and mortality statistics.
AB  - OBJECTIVES: To examine the geographical relation between mortality and
      deprivation in England and Wales at the start of the 20th and 21st centuries. To
      explore the evidence for a strengthening or weakening of this relation over the
      century and test for relations between the mortality and deprivation patterns of
      a century ago and modern mortality and causes of death. DESIGN: Census and
      mortality data for 634 districts from the 1900s directly compared with
      interpolated ward level data from 2001. SETTING: Census data and national
      statistics for England and Wales in the 1900s and 2001. Population Entire
      population in both periods. MAIN OUTCOME MEASURES: Standardised mortality ratios
      for all districts for both periods with additional cause specific ratios
      calculated for 2001. Deprivation (Carstairs) scores for each district in 2001,
      with comparable measure created for the 1900s. Correlations and partial
      correlations between deprivation scores and standardised mortality ratios in the
      1900s and 2001 for the 614 districts for which all data were available. RESULTS:
      The was no evidence of a significant change in the strength of the relation
      between deprivation and mortality between the start and end of the 20th century.
      Modern patterns of mortality and deprivation remain closely related to the
      patterns of a century ago. Even after adjustment for modern deprivation,
      standardised mortality ratios from the 1900s show a significant correlation with
      modern mortality and most modern causes of death. Conversely, however, there was
      no significant relation between deprivation in the 1900s and modern mortality for
      most causes of death after adjustment for modern deprivation. CONCLUSIONS:
      Despite all the medical, public health, social, economic, and political changes
      over the 20th century, patterns of poverty and mortality and the relations
      between them remain firmly entrenched. There is a strong relation between the
      mortality levels of a century ago and those of today. This goes beyond what would
      have been expected from the continuing relation between deprivation and mortality
      and holds true for most major modern causes of death.

PMID- 19744976
TI  - Use of qualitative methods alongside randomised controlled trials of complex
      healthcare interventions: methodological study.
AB  - OBJECTIVE: To examine the use of qualitative approaches alongside randomised
      trials of complex healthcare interventions. DESIGN: Review of randomised
      controlled trials of interventions to change professional practice or the
      organisation of care. DATA SOURCES: Systematic sample of 100 trials published in
      English from the register of the Cochrane Effective Practice and Organisation of
      Care Review Group. METHODS: Published and unpublished qualitative studies linked
      to the randomised controlled trials were identified through database searches and
      contact with authors. Data were extracted from each study by two reviewers using
      a standard form. We extracted data describing the randomised controlled trials
      and qualitative studies, the quality of these studies, and how, if at all, the
      qualitative and quantitative findings were combined. A narrative synthesis of the
      findings was done. RESULTS: 30 of the 100 trials had associated qualitative work
      and 19 of these were published studies. 14 qualitative studies were done before
      the trial, nine during the trial, and four after the trial. 13 studies reported
      an explicit theoretical basis and 11 specified their methodological approach.
      Approaches to sampling and data analysis were poorly described. For most cases
      (n=20) we found no indication of integration of qualitative and quantitative
      findings at the level of either analysis or interpretation. The quality of the
      qualitative studies was highly variable. CONCLUSIONS: Qualitative studies
      alongside randomised controlled trials remain uncommon, even where relatively
      complex interventions are being evaluated. Most of the qualitative studies were
      carried out before or during the trials with few studies used to explain trial
      results. The findings of the qualitative studies seemed to be poorly integrated
      with those of the trials and often had major methodological shortcomings.

PMID- 19744977
TI  - Intracellular antimicrobial activity appearing as a relevant factor in antibiotic
      efficacy against an experimental foreign-body infection caused by Staphylococcus
      aureus.
AB  - OBJECTIVES: The presence of bacterial biofilm, tolerance to antibiotics and
      dysfunctional activity of phagocytic cells are all related to difficulties in
      eradicating foreign-body infections. We aimed to quantify the presence of
      intracellular Staphylococcus aureus and to study the extent to which the
      intracellular activity of antibiotics might determine their efficacy against an
      experimental rat tissue-cage model of foreign-body infection. METHODS: Using this
      model, animals were treated for 7 days with 100 mg/kg/day levofloxacin or 200
      mg/kg/12 h cloxacillin, or were left untreated. Antibiotic efficacy was evaluated
      by means of bacterial counts from tissue-cage fluid (TCF); these counts were
      derived separately in total, intracellular and extracellular bacteria. The
      presence of intracellular bacteria was checked by electron microscopy. Population
      analysis was performed with surviving bacteria recovered at the end of
      levofloxacin therapy. RESULTS: Among a total number of bacteria (mean log cfu/mL
      +/- SD) from TCF of 6.86 +/- 0.6, we identified 6.38 +/- 0.8 intracellular
      bacteria and 5.57 +/- 0.5 extracellular bacteria. Levofloxacin was more efficient
      than cloxacillin (P < 0.05) against both intracellular and extracellular
      bacteria. The killing activity of levofloxacin against the intracellular
      population was higher than against the extracellular bacteria (P = 0.1). The
      frequency of levofloxacin-resistant mutants among surviving bacteria at the end
      of levofloxacin therapy was similar to that for the wild-type strain.
      CONCLUSIONS: Intracellular bacteria accounted for the largest proportion of the
      total inoculum in this model of foreign-body infection. The intracellular
      activity of an antibiotic seems to be an additional relevant factor in the
      antibiotic response to these infections.

PMID- 19744978
TI  - Occurrence of vancomycin-tolerant and heterogeneous vancomycin-intermediate
      strains (hVISA) among Staphylococcus aureus causing bloodstream infections in
      nine USA hospitals.
AB  - BACKGROUND: The bactericidal activities of vancomycin and daptomycin were
      evaluated in a large collection of methicillin-resistant Staphylococcus aureus
      (MRSA) bacteraemia strains from nine major USA medical centres. OBJECTIVES: To
      evaluate the occurrence of heterogeneous vancomycin-intermediate S. aureus
      (hVISA) among MRSA strains tolerant to vancomycin and/or with increased
      vancomycin or daptomycin MIC values. The accuracy of the macro Etest method (MET)
      compared with population analysis profiling (PAP) for the detection of hVISA was
      also assessed. METHODS: A total of 1800 MRSA strains were collected from
      bloodstream infections at the nine sites (40 strains per year, per medical centre
      during the 2002-06 study period). Vancomycin and daptomycin MIC testing was
      performed by reference broth microdilution (all strains) and MBC tests on 50% of
      strains (randomly selected). A subset of isolates (n = 268) having an increased
      vancomycin MBC (> or =16 mg/L), an increased vancomycin MIC (> or =1 mg/L) and/or
      an increased daptomycin MIC (>0.5 mg/L) were tested for susceptibility to
      vancomycin and teicoplanin by MET. RESULTS: Overall, 181 of 900 (20.1%) MRSA
      tested exhibited vancomycin tolerance, varying from 10% to 43% among the medical
      centres evaluated, and from 11.7% in 2004 to 27.8% in 2005. No resistance trend
      was observed in any medical centre or in the overall study data. Daptomycin
      showed bactericidal activity against all strains tested. The accuracy of MET for
      identifying hVISA strains varied significantly with the criteria applied for
      positivity. CONCLUSIONS: The most frequently used criteria to define hVISA, i.e.
      MET reading values > or =8 mg/L for both vancomycin and teicoplanin or > or =12
      mg/L for teicoplanin only, detected 20 of 36 PAP-positive strains (55.6%
      sensitivity), indicating that the prevalence of hVISA could be higher than
      currently appreciated. Daptomycin was bactericidal against hVISA strains.

PMID- 19744979
TI  - Periplasmic adaptor protein AcrA has a distinct role in the antibiotic resistance
      and virulence of Salmonella enterica serovar Typhimurium.
AB  - OBJECTIVES: AcrA can function as the periplasmic adaptor protein (PAP) in several
      RND tripartite efflux pumps, of which AcrAB-TolC is considered the most
      important. This system confers innate multiple antibiotic resistance. Disruption
      of acrB or tolC impairs the ability of Salmonella Typhimurium to colonize and
      persist in the host. The aim of this study was to investigate the role of AcrA
      alone in multidrug resistance and pathogenicity. METHODS: The acrA gene was
      inactivated in Salmonella Typhimurium SL1344 by insertion of the aph gene and
      this mutant complemented with pWKS30acrA. The antimicrobial susceptibility of the
      mutant to six antibiotics as well as various dyes and detergents was determined.
      In addition, efflux activity was quantified. The ability of the mutant to adhere
      to, and invade, tissue culture cells in vitro was measured. RESULTS: Following
      disruption of acrA, RT-PCR and western blotting confirmed that acrB/AcrB was
      still expressed when acrA was disrupted. The acrA mutant was hypersusceptible to
      antibiotics, dyes and detergents. In some cases, lower MICs were seen than for
      the acrB or tolC mutants. Efflux of the fluorescent dye Hoechst H33342 was less
      than in wild-type following disruption of acrA. acrA was also required for
      adherence to, and invasion of, tissue culture cells. CONCLUSIONS: Inactivation of
      acrA conferred a phenotype distinct to that of acrB::aph and tolC::aph. These
      data indicate a role for AcrA distinct to that of other protein partners in both
      efflux of substrates and virulence.

PMID- 19744980
TI  - Rapid detection of CTX-M-producing Enterobacteriaceae in urine samples.
AB  - OBJECTIVES: CTX-M extended-spectrum beta-lactamases (ESBLs) are emerging
      worldwide. Fast and reliable detection techniques may become mandatory for
      implementing proper treatment and infection control measures. Here, a bla(CTX-M)
      specific LightCycler real-time PCR (LC-PCR) assay based on hybridization probes
      was developed. METHODS: Urine samples positive for Gram-negative bacilli as
      revealed by Gram staining were collected over a 3 month period at Bicetre
      hospital, France. Aliquots of these urine samples were frozen for subsequent
      molecular analysis, and the bacteria were cultured and identified by standard
      bacteriological techniques (biochemical tests, disc diffusion antibiogram and
      synergy testing). LC-PCR and standard PCR followed by sequencing was performed on
      all ESBL-positive and on 70 randomly chosen ESBL-negative urine samples. RESULTS:
      Over the study period, 810 urine samples were collected from 655 patients. Thirty
      six ESBL-producing Enterobacteriaceae, mostly Escherichia coli (77%), were
      identified from 29 patients, of which half were outpatients. Twenty-five urine
      samples (19 patients) were found to be positive for bla(CTX-M) genes using the LC
      PCR assay. The bla(CTX-M) genes belonged to the bla(CTX-M-1), bla(CTX-M-9) and
      bla(CTX-M-2) groups (68%, 24% and 8%, respectively). Standard PCR and sequencing
      of the entire bla(CTX-M) genes confirmed the LC-PCR results; 17 CTX-M-15, 6 CTX-M
      9 and 2 CTX-M-2. Among the remaining ESBLs, eight were of the TEM type and three
      of the SHV type. CONCLUSIONS: The LC-PCR assay represents a powerful tool for
      rapid identification of CTX-M producers in urine samples.

PMID- 19744981
TI  - In vitro synergy studies based on tazobactam/piperacillin against clinical
      isolates of metallo-beta-lactamase-producing Pseudomonas aeruginosa.

PMID- 19744982
TI  - Pharmacokinetics of novel antimicrobial cationic peptides NAB 7061 and NAB 739 in
      rats following intravenous administration.
AB  - OBJECTIVES: To determine the disposition of novel antimicrobial cationic peptides
      NAB 7061 and NAB 739 following intravenous administration in rats. METHODS:
      Sprague-Dawley rats received a single intravenous bolus of 1.0 mg/kg NAB 7061 or
      NAB 739. Plasma concentrations of NAB 7061 or NAB 739 were determined by HPLC or
      liquid chromatography-mass spectrometry. The pharmacokinetic parameters of NAB
      7061 and NAB 739 were calculated using non-compartmental analysis. RESULTS:
      Corresponding total body clearance, volume of distribution at steady state and
      terminal half-life of NAB 7061 and NAB 739 averaged 3.84 and 2.63 mL/min/kg, 339
      and 222 mL/kg, and 66.2 and 69.0 min, respectively. Approximately 7.16% and 19.4%
      of the dose was eliminated in an unchanged form via the urine in 24 h for NAB
      7061 and NAB 739, respectively. CONCLUSIONS: While both compounds had generally
      similar pharmacokinetics to colistin, even minor alterations in the chemical
      structures appear to have an impact on their pharmacokinetics, especially on
      their clearance by the kidney. There are also substantial differences in relation
      to the relative contributions of renal and non-renal clearance to overall
      elimination from the body.

PMID- 19744983
TI  - Response of Staphylococcus aureus to subinhibitory concentrations of a sequence
      selective, DNA minor groove cross-linking pyrrolobenzodiazepine dimer.
AB  - OBJECTIVES: ELB-21 is a pyrrolo[2,1-c][1,4]benzodiazepine dimer with potent
      antistaphylococcal activity; it binds covalently to guanine residues on opposing
      strands of duplex DNA, interfering with regulatory proteins and transcription
      elongation in a sequence-selective manner. Transcriptional and proteomic
      alterations induced by exposure of Staphylococcus aureus clinical isolate EMRSA
      16 to ELB-21 were determined in order to define more precisely the bactericidal
      mechanism of the drug. METHODS: DNase I footprinting was used to identify high
      affinity DNA binding sites. Microarrays and gel electrophoresis were used to
      assess the ELB-21-induced phenotype. RESULTS: High-affinity interstrand binding
      sites in which guanine residues were separated by 4 bp, and also some intrastrand
      cross-linking sites of variable length were identified. Exposure of EMRSA-16 to
      0.015 mg/L ELB-21 elicited a 2-fold or greater up-regulation of 168 genes in
      logarithmic phase and 181 genes in stationary phase; the majority of genes
      affected were associated with resident prophages Sa2 and Sa3, pathogenicity
      island SaPI4 and DNA damage repair. ELB-21 induced a marked increase in the
      number of viable phage particles in culture supernatants. The expression of only
      a limited number of genes showed a >50% reduction. Sixteen extracellular and four
      intracellular proteins were differentially expressed during logarithmic and
      stationary phases, including RecA, proteins associated with staphylococcal
      pathogenesis (IsaA, CspA), cell division and wall synthesis. CONCLUSIONS: ELB-21
      kills S. aureus by forming multiple interstrand and intrastrand DNA cross-links,
      resulting in induction of the DNA damage response, derepression of resident
      prophages and modulation of a limited number of genes involved with cell wall
      synthesis.

PMID- 19744984
TI  - Has the publication of methicillin-resistant Staphylococcus aureus (MRSA)
      treatment guidelines increased the survival associated with MRSA bacteraemia?
AB  - OBJECTIVES: To establish whether local practice review and national methicillin
      resistant Staphylococcus aureus (MRSA) treatment guidelines have increased the
      survival of patients with MRSA bacteraemia. METHODS: A multisite retrospective
      analysis of survival of patients with MRSA bacteraemia, which included patients
      from March 1995 to December 2008. Periods before and after the publication of UK
      guidelines were compared. RESULTS: Data were analysed for 1675 patients with a
      mean age of 69.8 years. Survival for the period up to and including 2003 was
      64.3%, and was 62.8% for both 2004-2005 and 2006-2008. CONCLUSIONS: No
      significant difference in survival in relation to local practice review or the
      publication of national guidelines was detected.

PMID- 19744985
TI  - Posaconazole attenuates leukotriene B4 release and uptake of calcium by
      chemoattractant-activated human neutrophils: a potential strategy to control
      neutrophil-mediated inflammation.
AB  - OBJECTIVES: This study was designed to investigate the neutrophil-targeted anti
      inflammatory potential of posaconazole (0.1-5 microM, equivalent to 0.7-3.9 mg/L)
      by measuring the effects of this agent on the release of leukotriene B(4)
      (LTB(4)) and store-operated uptake of Ca(2+) following stimulation of human
      neutrophils with platelet-activating factor (200 nM). METHODS: LTB(4) release and
      uptake of Ca(2+) by the cells were measured using an enzyme immunoassay and fura
      2/AM-based spectrofluorimetric procedures, respectively. RESULTS: Treatment of
      neutrophils with posaconazole resulted in dose-related attenuation of PAF
      activated release of LTB(4) and influx of Ca(2+), which attained statistical
      significance at 1 microM of the antimycotic. CONCLUSIONS: Although primarily an
      antimycotic, posaconazole possesses secondary anti-inflammatory activities, which
      may contribute to the therapeutic efficacy of this agent in patients with sepsis.

PMID- 19744986
TI  - Daily 300 mg dose of linezolid for the treatment of intractable multidrug
      resistant and extensively drug-resistant tuberculosis--authors' response.

PMID- 19744987
TI  - Defects in glycopeptidolipid biosynthesis confer phage I3 resistance in
      Mycobacterium smegmatis.
AB  - Mycobacteriophages have played an important role in the development of genetic
      tools and diagnostics for pathogenic mycobacteria, including Mycobacterium
      tuberculosis. However, despite the isolation of numerous phages that infect
      mycobacteria, the mechanisms of mycobacteriophage infection remain poorly
      understood, and knowledge about phage receptors is minimal. In an effort to
      identify the receptor for phage I3, we screened a library of Mycobacterium
      smegmatis transposon mutants for phage-resistant strains. All four phage I3
      resistant mutants isolated were found to have transposon insertions in genes
      located in a cluster involved in the biosynthesis of the cell-wall-associated
      glycopeptidolipid (GPL), and consequently the mutants did not synthesize GPLs.
      The loss of GPLs correlated specifically with phage I3 resistance, as all mutants
      retained sensitivity to two other mycobacteriophages: D29 and Bxz1. In order to
      define the minimal receptor for phage I3, we then tested the phage sensitivity of
      previously described GPL-deficient mutants of M. smegmatis that accumulate
      biosynthesis intermediates of GPLs. The results indicated that, while the removal
      of most sugar residues from the fatty acyl tetrapeptide (FATP) core of GPL did
      not affect sensitivity to phage I3, a single methylated rhamnose, transferred by
      the rhamnosyltransferase Gtf2 to the FATP core, was critical for phage binding.

PMID- 19744988
TI  - Degradation of chloroaromatics by Pseudomonas putida GJ31: assembled route for
      chlorobenzene degradation encoded by clusters on plasmid pKW1 and the chromosome.
AB  - Pseudomonas putida GJ31 has been reported to grow on chlorobenzene using a meta
      cleavage pathway with chlorocatechol 2,3-dioxygenase (CbzE) as a key enzyme. The
      CbzE-encoding gene was found to be localized on the 180 kb plasmid pKW1 in a
      cbzTEXGS cluster, which is flanked by transposases and encodes only a partial
      (chloro)catechol meta-cleavage pathway comprising ferredoxin reductase,
      chlorocatechol 2,3-dioxygenase, an unknown protein, 2-hydroxymuconic semialdehyde
      dehydrogenase and glutathione S-transferase. Downstream of cbzTEXGS are located
      cbzJ, encoding a novel type of 2-hydroxypent-2,4-dienoate hydratase, and a
      transposon region highly similar to Tn5501. Upstream of cbzTEXGS, traNEOFG
      transfer genes were found. The search for gene clusters possibly completing the
      (chloro)catechol metabolic pathway of GJ31 revealed the presence of two
      additional catabolic gene clusters on pKW1. The mhpRBCDFETP cluster encodes
      enzymes for the dissimilation of 2,3-dihydroxyphenylpropionate in a novel
      arrangement characterized by the absence of a gene encoding 3-(3
      hydroxyphenyl)propionate monooxygenase and the presence of a GntR-type regulator,
      whereas the nahINLOMKJ cluster encodes part of the naphthalene metabolic pathway.
      Transcription studies supported their possible involvement in chlorobenzene
      degradation. The upper pathway cluster, comprising genes encoding a chlorobenzene
      dioxygenase and a chlorobenzene dihydrodiol dehydrogenase, was localized on the
      chromosome. A high level of transcription in response to chlorobenzene revealed
      it to be crucial for chlorobenzene degradation. The chlorobenzene degradation
      pathway in strain GJ31 is thus a mosaic encoded by four gene clusters.

PMID- 19744989
TI  - Genetic diversity and stability of the porA allele as a genetic marker in human
      Campylobacter infection.
AB  - The major outer-membrane protein (MOMP) of Campylobacter jejuni and Campylobacter
      coli, encoded by the porA gene, is extremely genetically diverse. Conformational
      MOMP epitopes are important in host immunity, and variation in surface-exposed
      regions probably occurs as a result of positive immune selection during
      infection. porA diversity has been exploited in genotyping studies using highly
      discriminatory nucleotide sequences to identify potentially epidemiologically
      linked cases of human campylobacteriosis. To understand the overall nature and
      extent of porA diversity and stability in C. jejuni and C. coli we investigated
      sequences in isolates (n=584) obtained from a defined human population (approx.
      600,000) over a defined time period (1 year). A total of 196 distinct porA
      variants were identified. Regions encoding putative extracellular loops were the
      most variable in both nucleotide sequence and length. Phylogenetic analysis
      identified three porA allele clusters that originated in (i) predominantly C.
      jejuni and a few C. coli, (ii) solely C. jejuni or (iii) predominantly C. coli
      and a few C. jejuni. The stability of porA within an individual human host was
      investigated using isolates cultured longitudinally from 64 sporadic cases, 27 of
      which had prolonged infection lasting between 5 and 98 days (the remainder having
      illness of normal duration, 0-4 days), and 20 cases from family outbreaks.
      Evidence of mutation was detected in two patients with prolonged illness. Despite
      demonstrable positive immune selection in these two unusual cases, the
      persistence of numerous variants within the population indicated that the porA
      allele is a valuable tool for use in extended typing schemes.

PMID- 19744990
TI  - Genetic diversity of capsular polysaccharide biosynthesis in Klebsiella
      pneumoniae clinical isolates.
AB  - Klebsiella pneumoniae is an enteric pathogen causing community-acquired and
      hospital-acquired infections in humans. Epidemiological studies have revealed
      significant diversity in capsular polysaccharide (CPS) type and clinical
      manifestation of K. pneumoniae infection in different geographical areas of the
      world. We have sequenced the capsular polysaccharide synthesis (cps) region of
      seven clinical isolates and compared the sequences with the publicly available
      cps sequence data of five strains: NTUH-K2044 (K1 serotype), Chedid (K2
      serotype), MGH78578 (K52 serotype), A1142 (K57 serotype) and A1517. Among all
      strains, six genes at the 5' end of the cps clusters that encode proteins for CPS
      transportation and processing at the bacterial surface are highly similar to each
      other. The central region of the cps gene clusters, which encodes proteins for
      polymerization and assembly of the CPS subunits, is highly divergent. Based on
      the collected sequence, we found that either the wbaP gene or the wcaJ gene
      exists in a given K. pneumoniae strain, suggesting that there is a major
      difference in the CPS biosynthesis pathway and that the K. pneumoniae strains can
      be classified into at least two distinct groups. All isolates contain gnd,
      encoding gluconate-6-phosphate dehydrogenase, at the 3' end of the cps gene
      clusters. The rmlBADC genes were found in CPS K9-positive, K14-positive and K52
      positive strains, while manC and manB were found in K1, K2, K5, K14, K62 and two
      undefined strains. Our data indicate that, while overall genomic organization is
      similar between different pathogenic K. pneumoniae strains, the genetic variation
      of the sugar moiety and polysaccharide linkage generate the diversity in CPS
      molecules that could help evade host immune attack.

PMID- 19744991
TI  - Two type IV secretion systems with different functions in Burkholderia
      cenocepacia K56-2.
AB  - Bacterial type IV secretion systems (T4SS) perform two fundamental functions
      related to pathogenesis: the delivery of effector molecules to eukaryotic target
      cells, and genetic exchange. Two T4SSs have been identified in Burkholderia
      cenocepacia K56-2, a representative of the ET12 lineage of the B. cepacia complex
      (Bcc). The plant tissue watersoaking (Ptw) T4SS encoded on a resident 92 kb
      plasmid is a chimera composed of VirB/D4 and F-specific subunits, and is
      responsible for the translocation of effector(s) that have been linked to the Ptw
      phenotype. The bc-VirB/D4 system located on chromosome II displays homology to
      the VirB/D4 T4SS of Agrobacterium tumefaciens. In contrast to the Ptw T4SS, the
      bc-VirB/D4 T4SS was found to be dispensable for Ptw effector(s) secretion, but
      was found to be involved in plasmid mobilization. The fertility inhibitor Osa did
      not affect the secretion of Ptw effector(s) via the Ptw system, but did disrupt
      the mobilization of a RSF1010 derivative plasmid.

PMID- 19744992
TI  - Retinoic acids induce neurosteroid biosynthesis in human glial GI-1 Cells via the
      induction of steroidogenic genes.
AB  - The steroids synthesized in the central nervous system (CNS) are the
      neurosteroids. Since little information is currently available concerning the
      roles of the retinoic acids (RAs) during steroidogenesis in the CNS, we
      investigated the effects of RAs upon their synthesis in our current study.
      Specifically, we analyzed the effects of all-trans-retinoic acid (ATRA) upon the
      expression of neurosteroid biosynthesis genes in the human glial cell line GI-1,
      in which the major steroidogenic genes are expressed. Treatment with ATRA (10
      muM) induced a 4.9-fold increase in the expression of the cytochrome P450scc
      (CYP11A1) gene, the product of which cleaves the cholesterol side chain, a rate
      limiting step during steroidogenesis. ATRA also strongly induced the expression
      of steroidogenic acute regulatory protein (StAR) and 3beta-hydroxysteroid
      dehydrogenase (3beta-HSD) (an increase of 5- and 50-fold, respectively). A
      retinoic acid receptor (RAR)-specific agonist, TTNPB, was unable to mimic this
      induction whereas a retinoid X receptor (RXR)-specific agonist, methoprene acid,
      in addition to 9-cis-RA, could do so. These data indicate that ATRA is isomerized
      to 9-cis-RA in the culture medium, as reported previously, and that 9-cis-RA
      activates the RXR. In addition, ATRA also induced the de novo synthesis of
      neurosteroids such as pregnenolone and progesterone. These results suggest that
      ATRA might induce the de novo neurosteroid synthesis via the induction of
      steroidogenic genes in human glial cells. The multiple effects of vitamin A upon
      CNS functions might therefore be partly explained by the induction of
      neurosteroidogenesis by RAs, since neurosteroids have also been reported to have
      multiple effects in the CNS.

PMID- 19744993
TI  - QuickGO: a web-based tool for Gene Ontology searching.
AB  - QuickGO is a web-based tool that allows easy browsing of the Gene Ontology (GO)
      and all associated electronic and manual GO annotations provided by the GO
      Consortium annotation groups QuickGO has been a popular GO browser for many
      years, but after a recent redevelopment it is now able to offer a greater range
      of facilities including bulk downloads of GO annotation data which can be
      extensively filtered by a range of different parameters and GO slim set
      generation. AVAILABILITY AND IMPLEMENTATION: QuickGO has implemented in
      JavaScript, Ajax and HTML, with all major browsers supported. It can be queried
      online at http://www.ebi.ac.uk/QuickGO. The software for QuickGO is freely
      available under the Apache 2 licence and can be downloaded from
      http://www.ebi.ac.uk/QuickGO/installation.html

PMID- 19744994
TI  - Phenotypic categorization of genetic skin diseases reveals new relations between
      phenotypes, genes and pathways.
AB  - MOTIVATION: Systematic analysis of connection between proteins, their cellular
      function and phenotypic manifestations in disease is a central problem of
      biological and clinical research. The solution to this problem requires the
      development of new approaches to link the rapidly growing dataset of gene-disease
      associations with the many complex and overlapping phenotypes of human disease.
      RESULTS: We analyze genetic skin disorders and suggest a manually designed set of
      elementary phenotypes whose combinations define diseases as points in a
      multidimensional space, providing a basis for phenotypic disease clustering.
      Placing the known gene-disease associations in the context of this space reveals
      new patterns that suggest previously unknown functional links between proteins,
      signaling pathways and disease phenotypes. For example, analysis of
      telangiectasias (spider vein diseases) reveals a previously unrecognized
      interplay between the TGF-beta signaling pathway and pentose phosphate pathway.
      This interaction may mediate glucose-dependent regulation of TGF-beta signaling,
      providing a clue to the known association between angiopathies and diabetes and
      implying new gene candidates for mutational analysis and drug targeting.

PMID- 19744995
TI  - CCHMM_PROF: a HMM-based coiled-coil predictor with evolutionary information.
AB  - MOTIVATION: The widespread coiled-coil structural motif in proteins is known to
      mediate a variety of biological interactions. Recognizing a coiled-coil
      containing sequence and locating its coiled-coil domains are key steps towards
      the determination of the protein structure and function. Different tools are
      available for predicting coiled-coil domains in protein sequences, including
      those based on position-specific score matrices and machine learning methods.
      RESULTS: In this article, we introduce a hidden Markov model (CCHMM_PROF) that
      exploits the information contained in multiple sequence alignments (profiles) to
      predict coiled-coil regions. The new method discriminates coiled-coil sequences
      with an accuracy of 97% and achieves a true positive rate of 79% with only 1% of
      false positives. Furthermore, when predicting the location of coiled-coil
      segments in protein sequences, the method reaches an accuracy of 80% at the
      residue level and a best per-segment and per-protein efficiency of 81% and 80%,
      respectively. The results indicate that CCHMM_PROF outperforms all the existing
      tools and can be adopted for large-scale genome annotation. AVAILABILITY: The
      dataset is available at http://www.biocomp.unibo.it/ approximately lisa/coiled
      coils. The predictor is freely available at
      http://gpcr.biocomp.unibo.it/cgi/predictors/cchmmprof/pred_cchmmprof.cgi.
      CONTACT: piero@biocomp.unibo.it.

PMID- 19744996
TI  - De novo computational prediction of non-coding RNA genes in prokaryotic genomes.
AB  - MOTIVATION: The computational identification of non-coding RNA (ncRNA) genes
      represents one of the most important and challenging problems in computational
      biology. Existing methods for ncRNA gene prediction rely mostly on homology
      information, thus limiting their applications to ncRNA genes with known
      homologues. RESULTS: We present a novel de novo prediction algorithm for ncRNA
      genes using features derived from the sequences and structures of known ncRNA
      genes in comparison to decoys. Using these features, we have trained a neural
      network-based classifier and have applied it to Escherichia coli and Sulfolobus
      solfataricus for genome-wide prediction of ncRNAs. Our method has an average
      prediction sensitivity and specificity of 68% and 70%, respectively, for
      identifying windows with potential for ncRNA genes in E.coli. By combining
      windows of different sizes and using positional filtering strategies, we
      predicted 601 candidate ncRNAs and recovered 41% of known ncRNAs in E.coli. We
      experimentally investigated six novel candidates using Northern blot analysis and
      found expression of three candidates: one represents a potential new ncRNA, one
      is associated with stable mRNA decay intermediates and one is a case of either a
      potential riboswitch or transcription attenuator involved in the regulation of
      cell division. In general, our approach enables the identification of both cis-
      and trans-acting ncRNAs in partially or completely sequenced microbial genomes
      without requiring homology or structural conservation. AVAILABILITY: The source
      code and results are available at
      http://csbl.bmb.uga.edu/publications/materials/tran/.

PMID- 19744997
TI  - Measuring the sensitivity of single-locus "neutrality tests" using a direct
      perturbation approach.
AB  - A large number of statistical tests have been proposed to detect natural
      selection based on a sample of variation at a single genetic locus. These tests
      measure the deviation of the allelic frequency distribution observed within
      populations from the distribution expected under a set of assumptions that
      includes both neutral evolution and equilibrium population demography. The
      present study considers a new way to assess the statistical properties of these
      tests of selection, by their behavior in response to direct perturbations of the
      steady-state allelic frequency distribution, unconstrained by any particular
      nonequilibrium demographic scenario. Results from Monte Carlo computer
      simulations indicate that most tests of selection are more sensitive to
      perturbations of the allele frequency distribution that increase the variance in
      allele frequencies than to perturbations that decrease the variance. Simulations
      also demonstrate that it requires, on average, 4N generations (N is the diploid
      effective population size) for tests of selection to relax to their theoretical,
      steady-state distributions following different perturbations of the allele
      frequency distribution to its extremes. This relatively long relaxation time
      highlights the fact that these tests are not robust to violations of the other
      assumptions of the null model besides neutrality. Lastly, genetic variation
      arising under an example of a regularly cycling demographic scenario is
      simulated. Tests of selection performed on this last set of simulated data
      confirm the confounding nature of these tests for the inference of natural
      selection, under a demographic scenario that likely holds for many species. The
      utility of using empirical, genomic distributions of test statistics, instead of
      the theoretical steady-state distribution, is discussed as an alternative for
      improving the statistical inference of natural selection.

PMID- 19744998
TI  - Molecular phylogenetics, temporal diversification, and principles of evolution in
      the mustard family (Brassicaceae).
AB  - Brassicaceae is an important family at both the agronomic and scientific level.
      The family not only includes several model species, but it is also becoming an
      evolutionary model at the family level. However, resolving the phylogenetic
      relationships within the family has been problematic, and a large-scale molecular
      phylogeny in terms of generic sampling and number of genes is still lacking. In
      particular, the deeper relationships within the family, for example between the
      three major recognized lineages, prove particularly hard to resolve. Using a slow
      evolving mitochondrial marker (nad4 intron 1), we reconstructed a comprehensive
      phylogeny in generic representation for the family. In addition, and because
      resolution was very low in previous single marker phylogenies, we adopted a
      supermatrix approach by concatenating all checked and reliable sequences
      available on GenBank as well as new sequences for a total 207 currently
      recognized genera and eight molecular markers representing a comprehensive
      coverage of all three genomes. The supermatrix was dated under an uncorrelated
      relaxed molecular clock using a direct fossil calibration approach. Finally, a
      lineage-through-time-plot and rates of diversification for the family were
      generated. The resulting tree, the largest in number of genera and markers
      sampled to date and covering the whole family in a representative way, provides
      important insights into the evolution of the family on a broad scale. The
      backbone of the tree remained largely unresolved and is interpreted as the
      consequence of early rapid radiation within the family. The age of the family was
      inferred to be 37.6 (24.2-49.4) Ma, which largely agrees with previous studies.
      The ages of all major lineages and tribes are also reported. Analysis of
      diversification suggests that Brassicaceae underwent a rapid period of
      diversification, after the split with the early diverging tribe Aethionemeae.
      Given the dates found here, the family appears to have originated under a warm
      and humid climate approximately 37 Ma. We suggest that the rapid radiation
      detected was caused by a global cooling during the Oligocene coupled with a
      genome duplication event. This duplication could have allowed the family to
      rapidly adapt to the changing climate.

PMID- 19744999
TI  - Analysis of the immunoglobulin light chain genes in zebra finch: evolutionary
      implications.
AB  - All jawed vertebrates produce immunoglobulins (IGs) as a defense mechanism
      against pathogens. Typically, IGs are composed of two identical heavy chains
      (IGH) and two identical light chains (IGL). Most tetrapod species encode more
      than one isotype of light chains. Chicken is the only representative of birds for
      which genomic information is currently available and is an exception to the above
      rule because it encodes only a single IGL isotype (i.e., lambda). Here, we show
      that the genome of zebra finch, another bird species, encodes a single IGL
      isotype, that is, lambda, like the chicken. These results strongly suggest that
      the second isotype (i.e., kappa) present in both reptiles and mammals was lost in
      a very early stage of bird evolution. Furthermore, we show that both chicken and
      zebra finch contain a single set of functional variable, joining, and constant
      region genes and multiple variable region pseudogenes. The latter finding
      suggests that this type of genomic organization was already present in the common
      ancestor of these bird species and remained unchanged over a long evolutionary
      time. This conservation is in contrast with the high levels of variation observed
      in the mammalian IGL loci. The presence of a single functional variable region
      gene followed by multiple variable pseudogenes in zebra finch suggest that this
      species may be generating antibody diversity by a gene conversion-like mechanism
      like the chicken.

PMID- 19745001
TI  - Selection to maintain paralogous amino acid differences under the pressure of
      gene conversion in the heat-shock protein genes in yeast.
AB  - A genome scan for the signatures of selection for paralogous functional amino
      acid differences was performed with yeast genomes. This recently developed method
      makes it possible to localize the target sites of selection under the pressure of
      gene conversion. We found that two gene pairs have strong signatures of
      selection. The two pairs of duplicated genes happened to be heat shock genes
      (Ssa1/ Ssa2 and Ssb1/Ssb2), which have similar protein structures to each other,
      although the amino acid sequence identity between Ssa and Ssb is not high (
      approximately 60%). Interestingly, the two gene pairs exhibit signature of
      selection at almost identical positions within the substrate-binding domain beta.
      Because this domain specifies the substrate polypeptides, it is presumed that
      functional divergence may be advantageous in this domain. Evolutionary analysis
      demonstrated that the observed divergence in the two gene pairs has been
      maintained in many yeast species independently, suggesting long-term operation of
      strong selection.

PMID- 19745000
TI  - Lower linkage disequilibrium at CNVs is due to both recurrent mutation and
      transposing duplications.
AB  - Copy number variants (CNVs) within humans can have both adaptive and deleterious
      effects. Because of their phenotypic significance, researchers have attempted to
      find single nucleotide polymorphisms (SNPs) in high linkage disequilibrium (LD)
      with CNVs to use in genomewide association studies. However, studies have found
      that CNVs are less likely to be in strong LD with flanking markers. We
      hypothesized that this "taggability gap" can be explained by duplication events
      that place paralogous sequences far apart. In support of our hypothesis, we find
      that duplications are significantly less likely than deletions to have a "tag"
      SNP, even after controlling for CNV length, allele frequency, and availability of
      appropriate flanking SNPs. Using a novel likelihood method, we are able to show
      that many complex CNVs--those due to multiple duplication or deletion
      polymorphisms--are made up of two loci with little LD between them. Additionally,
      we find that many polymorphic duplications detected in a recent clone-based study
      are located far from their parental loci. We also examine two other common
      hypotheses for the taggability gap, and find that recurrent mutation of both
      deletions and duplications appears to have an effect on LD, but that lower SNP
      density around CNVs has no effect. Overall, our results suggest that a
      substantial fraction of CNVs caused by duplication cannot be tagged by markers
      flanking the parental locus because they have changed genomic location.

PMID- 19745002
TI  - Unerupted incisors--characteristic features and associated anomalies.
AB  - The aims of this study were to investigate the association of unerupted incisors
      with other dental anomalies and to indicate the aetiological and clinical
      relevance of such associations. Forty-one patients with unerupted incisors were
      examined. The group comprised 30 males and 11 females, ranging in age from 7 to
      39 years. The patients were assessed for nine dental anomalies: hyperdontia,
      hypodontia, microdontia, enamel hypoplasia, infraocclusion of the primary molars
      and ectopia of the canines, premolars, first permanent molars, and second
      permanent molars. The patients were matched with respect to age and gender to 41
      consecutively selected control subjects with similar selection criteria but no
      history of problems with incisor eruption. The prevalence rates of the dental
      anomalies in association with failure of eruption of incisors were compared to
      the reference rates in the control group by means of Pearson chi-square tests.
      The results of this study revealed that unerupted incisors were more frequent in
      males than in females. A statistically significant association (P = 0.006) was
      found between unerupted incisors and other inherited dental anomalies, namely
      ectopic teeth, hyperdontia, and enamel hypoplasia. Unerupted incisors may be
      considered part of a spectrum of inheritable dental anomalies.

PMID- 19745003
TI  - Psychosocial development in a Danish population of children with cochlear
      implants and deaf and hard-of-hearing children.
AB  - Research has shown a prevalence of psychosocial difficulties ranging from about
      20% to 50% among children with hearing loss. This study evaluates the prevalence
      of psychosocial difficulties in a Danish population in relation to different
      explanatory variables. Five scales and questionnaires measuring sign language,
      spoken language, hearing abilities, and psychosocial difficulties were given to
      334 children with hearing loss. Results show that the prevalence of psychosocial
      difficulties was 3.7 times greater compared with a group of hearing children. In
      the group of children with additional disabilities, the prevalence was 3 times
      greater compared with children without additional disabilities. If sign language
      and/or oral language abilities are good, the children do not have a substantially
      higher level of psychosocial difficulties than do hearing children. This study
      documents the importance of communication-no matter the modality or degree of
      hearing loss-for the psychosocial well-being of hearing-impaired children.

PMID- 19745004
TI  - Inhibitory Effects of Ethyl Acetate Extract of Andrographis paniculata on NF
      kappaB Trans-Activation Activity and LPS-Induced Acute Inflammation in Mice.
AB  - This study was to investigate anti-inflammatory effect of Andrographis paniculata
      (Burm. f.) Nees (Acanthaceae) (AP). The effects of ethyl acetate (EtOAc) extract
      from AP on the level of inflammatory mediators were examined first using nuclear
      factor kappa B (NF-kappaB) driven luciferase assay. The results showed that AP
      significantly inhibited NF-kappaB luciferase activity and tumor necrosis factor
      alpha (TNF-alpha), interleukin 6 (IL-6), macrophage inflammatory protein-2 (MIP
      2) and nitric oxide (NO) secretions from lipopolysaccharide (LPS)/interferon
      gamma stimulated Raw264.7 cells. To further evaluate the anti-inflammatory
      effects of AP in vivo, BALB/c mice were tube-fed with 0.78 (AP1), 1.56 (AP2),
      3.12 (AP3) and 6.25 (AP4) mg kg(-1) body weight (BW)/day in soybean oil, while
      the control and PDTC (pyrrolidine dithiocarbamate, an anti-inflammatory agent)
      groups were tube-fed with soybean oil only. After 1 week of tube-feeding, the
      PDTC group was injected with 50 mg kg(-1) BW PDTC and 1 h later, all of the mice
      were injected with 15 mg kg(-1) BW LPS. The results showed that the AP1, AP2, AP3
      and PDTC groups, but not AP4, had significantly higher survival rate than the
      control group. Thus, the control, AP1, AP2, AP3 and PDTC groups were repeated for
      in vivo parameters. The results showed that the AP and PDTC groups had
      significantly lower TNF-alpha, IL-12p40, MIP-2 or NO in serum or peritoneal
      macrophages and infiltration of inflammatory cells into the lung of mice. The AP1
      group also had significantly lower MIP-2 mRNA expression in brain. This study
      suggests that AP can inhibit the production of inflammatory mediators and
      alleviate acute hazards at its optimal dosages.

PMID- 19745005
TI  - Contributions of sasang constitutional medicine.

PMID- 19745006
TI  - Could there be a Synthesis between Western and Oriental Medicine, and with Sasang
      Constitutional Medicine in Particular?
AB  - Attitudes towards oriental medicine are changing for two major reasons. The first
      is that many patients, even in the West, are choosing to use its practitioners
      and methods. The second is that the rise of Systems Biology may offer a better
      basis for dialogue, and even for synthesis, between the oriental and Western
      traditions. However, a lot of work is needed to clear the way for such dialogue
      and synthesis. Much of this work should be devoted to clarifying the meanings of
      the terms used, and the framework of theory and practice within which oriental
      methods operate. But it is also necessary for Systems Biology itself to mature as
      a discipline, particularly at the higher levels of biological organization since
      it is at these levels that oriental medicine derives its ideas and practice.
      Higher level Systems Biology could be a basis for interpretation of the Korean
      version of oriental medicine: Sasang constitutional medicine since it seeks
      patient specific analysis and treatment, and the mathematical methods of systems
      biology could be used to analyze the central concept of balance in Sasang.

PMID- 19745007
TI  - Sasang constitutional medicine as a holistic tailored medicine.
AB  - Sasang constitutional medicine (SCM) is a unique traditional Korean therapeutic
      alternative form of medicine. Based on the Yin and Yang theory and on
      Confucianism, humans are classified into four constitutions. These differ in
      terms of (i) sensitivity to certain groups of herbs and medicines, (ii)
      equilibrium among internal organic functions, (iii) physical features and (iv)
      psychological characteristics. We propose that two main axes in the
      physiopathology of SCM (food intake/waste discharge and consuming/storing Qi and
      body fluids) are equivalent to the process of internal-external exchange and
      catabolism/anabolism in modern physiology, respectively. We then used this
      hypothesis to discuss the physiological and pathological principles of SCM.
      Constitution-based medicine is based on the theory that some medicinal herbs and
      remedies are only appropriate for certain constitutions and can cause adverse
      effects in others. The constitutional approach of SCM share the same vision as
      tailored medicine; an individualized therapy that can minimize the risk of
      adverse reaction while increasing the efficacy and an individualized self
      regulation that can help prevent specific susceptible chronic disease and live
      healthily. There is still a long way to this goal for both SCM and tailored
      medicine, but we may benefit from systems approaches such as systems biology. We
      suggest that constitutional perspective of SCM and our hypothesis of two main
      processes may provide a novel insight for further studies.

PMID- 19745008
TI  - Psychological profile of sasang typology: a systematic review.
AB  - A systematic review of studies related to the psychological characteristics of
      Sasang types was conducted with the goal of delineating generalizable
      psychological profiles based on Sasang typology, a traditional Korean medical
      typology with medical herbs and acupuncture that is characterized as personalized
      medicine. Journal articles pertaining to Sasang typology were collected using
      five electronic database systems in Korea and in the USA. As a result, 64
      potentially relevant studies were identified and 21 peer-reviewed research
      articles that employed psychometric inventories were included. Beginning with the
      use of the Minnesota Multiphasic Personality Inventory in 1992, Myers-Briggs Type
      Indicator, NEO-Personality Inventory, Temperament and Character Inventory and
      other personality assessment tools were employed in the identified studies.
      Because data synthesis could not be carried out due to the heterogeneity of the
      studies, the present review article sought to delineate the mutual relevance of
      the studies based on research results pertaining to the correlation between the
      aforementioned psychological assessment instruments. Results of the review
      indicate that two super-factors, Extraversion and Neuroticism, serve as the
      foundation in regards to delineating personality constructs, such that the So
      Yang type scored high on the Extraversion dimension and low on the Neuroticism
      dimension, while the So-Eum type scored low on the Extraversion dimension and
      high on the Neuroticism dimension. The present systematic review indicates that
      Sasang typology shares similarities with the Western psychological tradition.

PMID- 19745009
TI  - Perspective of the human body in sasang constitutional medicine.
AB  - The Sasang constitutional medicine (SCM), a medical tradition originating from
      Korea, is distinguished from the traditional Chinese medicine in its
      philosophical background, theoretical development and especially, the fundamental
      rationale that analyzes the structure and function of the human body within a
      quadrifocal scheme. In SCM, the structure of the body is comprehended within the
      Sasang quadrifocal scheme, and the function of the body is understood within the
      context of the energy-fluid metabolism and the water-food metabolism controlled
      by the four main organs (lung, spleen, liver and kidney). Also, the concept of
      Seong-Jeong is used to explain the structural and functional variations between
      different constitutional types that arise from the constitutional variations in
      organ system scheme, which are in turn caused by deviations in the constitutional
      Seong-Jeong. Therefore, understanding the SCM perspective of the human body is
      essential in order to fully appreciate the advantages of the constitutional
      typological system (which focuses on individual idiosyncrasies) found in SCM.

PMID- 19745010
TI  - Current researches on the methods of diagnosing sasang constitution: an overview.
AB  - Sasang constitution diagnosis has traditionally been conducted by a Sasang
      constitutional medicine (SCM) doctor who examines the external appearance,
      temperament and various symptoms of an individual and then collectively analyzes
      this information to determine their own constitutions. However, because this
      process is subjective and not quantitative, many researchers have been attempting
      to develop objective and reasonable methods of determining constitutions. In
      Korea, even though a wide range of research regarding SCM has been conducted,
      most of the work has not been revealed internationally. So in this review, the
      authors have searched the Journal of Sasang Constitutional Medicine, as well as
      other Korean domestic journal databases and Pubmed for research regarding
      modernized constitution diagnosis methods so to provide the understanding of
      current research state and outlook for future research.

PMID- 19745011
TI  - Genetic approach to elucidation of sasang constitutional medicine.
AB  - Sasang Constitutional Medicine (SCM) offers a medical principle that classifies
      humans into four constitution groups and guides their treatment with constitution
      matched medical assistance. The principle of this traditional medicine, although
      requires significant scientific support, appears to suggest a genetic influence
      on constitution type. The relative frequency of constitution types in a
      population, for instance, has remained relatively constant since Jema Lee first
      described them from his observations. In addition, the body compartment concept
      of SCM appears to be related to the anterio-posterior patterning of the embryonic
      gut and associated internal organs. This study describes the attributes of the
      constitution concept of SCM that can be interpreted in the language of genetics
      and current approaches to identity the genetic factors that make up the
      constitution. These efforts should make it possible to interpret the principle of
      this traditional medicine scientifically. Considering the recent trend in
      medicine that pursues individualized or tailored medical offerings, once SCM is
      proven to be explainable with scientific evidence, it will be able to contribute
      to and take a place in the rapidly evolving medicine environment.

PMID- 19745012
TI  - Randomized clinical trials of constitutional acupuncture: a systematic review.
AB  - The aim of this systematic review is to compile and critically evaluate the
      evidence from randomized clinical trials (RCTs) for the effectiveness of
      acupuncture using constitutional medicine compared to standard acupuncture. Ten
      databases were searched through to December 2008 without language restrictions.
      We also hand-searched nine Korean journals of oriental medicine. We included
      prospective RCTs of any form of acupuncture with or without electrical
      stimulation. The included trials had to investigate constitutional medicine.
      There were no restrictions on population characteristics. Forty-one relevant
      studies were identified, and three RCTs were included. The methodological quality
      of the trials was variable. One RCT found Sasang constitutional acupuncture to be
      superior to standard acupuncture in terms of the Unified PD Rating Scale and
      freezing gate in Parkinson's disease (PD). Another two RCTs reported favorable
      effects of eight constitutional acupuncture on pain reduction in patients with
      herniated nucleus pulposi and knee osteoarthritis. Meta-analysis demonstrated
      positive results for eight constitutional acupuncture compared to standard
      acupuncture on pain reduction (weighted mean difference: 10 cm VAS, 1.69, 95% CI
      0.85-2.54, P < 0.0001; heterogeneity: tau(2) = 0.00, chi(2) = 0.00, P = 0.96,
      I(2) = 0%). Our results provide suggestive evidence for the effectiveness of
      constitutional acupuncture in treating pain conditions compared to standard
      acupuncture. However, the total number of RCTs and the total sample size included
      in our analysis were too small to draw definite conclusions. Future RCTs should
      assess larger patient samples with longer treatment periods and appropriate
      controls.

PMID- 19745013
TI  - Feature selection from a facial image for distinction of sasang constitution.
AB  - Recently, oriental medicine has received attention for providing personalized
      medicine through consideration of the unique nature and constitution of
      individual patients. With the eventual goal of globalization, the current trend
      in oriental medicine research is the standardization by adopting western
      scientific methods, which could represent a scientific revolution. The purpose of
      this study is to establish methods for finding statistically significant features
      in a facial image with respect to distinguishing constitution and to show the
      meaning of those features. From facial photo images, facial elements are analyzed
      in terms of the distance, angle and the distance ratios, for which there are
      1225, 61 250 and 749 700 features, respectively. Due to the very large number of
      facial features, it is quite difficult to determine truly meaningful features. We
      suggest a process for the efficient analysis of facial features including the
      removal of outliers, control for missing data to guarantee data confidence and
      calculation of statistical significance by applying ANOVA. We show the
      statistical properties of selected features according to different constitutions
      using the nine distances, 10 angles and 10 rates of distance features that are
      finally established. Additionally, the Sasang constitutional meaning of the
      selected features is shown here.

PMID- 19745014
TI  - Association between Genetic Polymorphism of Multidrug Resistance 1 Gene and
      Sasang Constitutions.
AB  - Multidrug resistance 1 (MDR1) is a gene that expresses P-glycoprotein (P-gp), a
      drug transporter protein. Genetic polymorphisms of MDR1 can be associated with
      Sasang constitutions because Sasang constitutional medicine (SCM) prescribes
      different drugs according to different constitutions. A Questionnaire for Sasang
      Constitution Classification II (QSCC II) was used to diagnose Sasang
      constitutions. Two hundred and seven healthy people whose Sasang constitutions
      had been identified were tested. Genotype analyses, restriction fragment length
      polymorphism (RFLP) and pyrosequencing were used in MDR1 C1236T, and in MDR1
      G2677T/A and C3435T, respectively. Significant differences in MDR1 C1236T
      genotypes were found between So-yangin and So-eumin. MDR1 G2677T/A genotype also
      showed significant differences in allele distribution between So-yangin and Tae
      eumin. So-yangin and So-eumin showed significant differences in the distribution
      of both 1236C-2677G-3435C and 1236T-2677G-3435T, haplotypes of MDR1. The genetic
      polymorphism of the MDR1 gene was thus shown to be an indicator that could
      distinguish So-yangin from other constitutions.

PMID- 19745015
TI  - Taeyeumjoweetang Affects Body Weight and Obesity-related Genes in Mice.
AB  - Taeyeumjoweetang (TYJWT) is a herbal medication that was mentioned in Jema Lee's
      Donguisusebowon, which is a book about Sasang constitutional medicine. Tae
      eumnis, one of the four constitutions, tend to suffer from metabolic diseases
      such as obesity and diabetes. It is widely used to treat the digestive problems
      and obesity of Tae-eumins. We divided mice that were fed a normal diet for 48
      days into control, TYJWT 250 mg kg(-1) and TYJWT 500 mg kg(-1) groups. After
      carrying out the experiments, the serum levels of leptin, adiponectin, ghrelin
      and resistin were measured. The results showed that TYJWT significantly reduced
      the weights of mice that were fed a normal diet, and that this was due to a
      decrease in food intake. Also, the two TYJWT groups had lower serum levels of
      leptin compared to the control group, and the ghrelin levels were proportionately
      increased by the dosage of TYJWT given. These results show that TYJWT has obesity
      suppressing effects similar to those previously reported using high fat diets. In
      addition, these results also provide evidence that TYJWT has anti-obesity
      effects.

PMID- 19745016
TI  - Analysis of skin humidity variation between sasang types.
AB  - The purpose of this study was to examine the relationship between variations in
      skin humidity (SH) induced by perspiration across Sasang types and to identify
      novel and effective Sasang classification factors. We also analyzed the responses
      of each Sasang type to sweating-related QSCC II items. The results revealed a
      significant difference in SH across gender and significant differences in SH
      before and after perspiration between Tae-Eum and So-Eum men. In addition, Tae
      Eum women showed significant differences in SH compared with women classified as
      another Sasang type. Furthermore, evaluation of the items related to sweating in
      the QSCC II and their relationship to each constitution revealed a significant
      difference between Tae-Eum and other Sasang types. Overall, the results of this
      study indicate that there is a distinct SH difference following perspiration
      between Tae-Eum and other Sasang types. Such findings may aid in Sasang typology
      diagnostic testing with the support of further sophisticated clinical studies.

PMID- 19745017
TI  - Quantitative Sasang Constitution Diagnosis Method for Distinguishing between Tae
      eumin and Soeumin Types Based on Elasticity Measurements of the Skin of the Human
      Hand.
AB  - The usefulness of constitutional diagnoses based on skin measurements has been
      established in oriental medicine. However, it is very difficult to standardize
      traditional diagnosis methods. According to Sasang constitutional medicine,
      humans can be distinguished based on properties of the skin, including its
      texture, roughness, hardness and elasticity. The elasticity of the skin was
      previously used to distinguish between people with Tae-eumin (TE) and Soeumin
      (SE) constitutions. The present study designed a system that uses a compression
      method to measure the elasticity of hand skin and evaluated its measurement
      repeatability. The proposed system was used to compare the skin elasticity
      between SE and TE subjects, which produced a measurement repeatability error of
      <3%. The proposed system is suitable for use as a quantitative constitution
      diagnosis method for distinguishing between TE and SE subjects with an acceptable
      level of uncertainty.

PMID- 19745018
TI  - Sasang constitution as a risk factor for diabetes mellitus: a cross-sectional
      study.
AB  - Sasang Constitutional Medicine, which is a branch of traditional Korean medicine,
      states that medications for diabetes should be individualized according to the
      patient's individual constitution. However, the effect of constitution on
      diabetes has not been evaluated to date. Therefore, this study was conducted to
      determine if constitution is an independent risk factor for diabetes by comparing
      the prevalence and odds ratios (ORs) of the disease according to constitution.
      The medical records of 1443 adults who had been examined and classified based on
      their constitution at Kyung Hee University Hospital in Seoul, Korea were
      reviewed. A chi-squared test and Fisher's exact test were used to compare the
      prevalence of diabetes according to constitution, and multiple logistic
      regression was used to calculate the ORs for diabetes. The prevalence of diabetes
      differed significantly according to constitution (chi(2) = 36.20, df = 2, P <
      0.001). Specifically, the prevalence of the disease was higher in Tae-eumin
      (11.4%) individuals than in Soyangin (5.0%) or Soeumin (1.7%) individuals. In
      addition, multiple logistic regression revealed that Tae-eumin individuals had a
      greater risk for diabetes than Soeumin individuals. When compared to Soeumin
      individuals, the adjusted ORs were 2.01 (95% CI 0.77-5.26) for Soyangin
      individuals and 3.96 (95% CI 1.48-10.60) for Tae-eumin individuals. These results
      show that constitution has a significant and independent association with
      diabetes, which suggests that constitution is an independent risk factor for
      diabetes that should be considered when attempting to detect and prevent the
      disease.

PMID- 19745019
TI  - Effects of aging on paired-pulse behavior of rat somatosensory cortical neurons.
AB  - Aging affects all levels of neural processing including changes of intracortical
      inhibition and cortical excitability. The paired-pulse stimulation protocol, the
      application of 2 stimuli in close succession, is used to investigate cortical
      excitability. The paired-pulse behavior is characterized by the fact that the
      second response is significantly suppressed at short interstimulus intervals
      (ISIs) but approaches the first response with increasing ISIs. However, there are
      controversial reports about the influence of age on paired-pulse behavior. We
      therefore used pairs of tactile stimuli (ISIs from tens to hundreds of
      milliseconds) to record extracellular responses of somatosensory cortical neurons
      of young and aged rats. Paired-pulse behavior was quantified as the ratio of the
      amplitude of the second response divided by the first. For all ISIs, we found
      significantly higher ratios in the old animals indicating reduced paired-pulse
      suppression (PPS). Evaluation of the single response components revealed a
      significant reduction of the response to the first stimulus for old animals but
      no age-dependent decrement to the second. Changes in PPS are usually mediated by
      modulating the second response characteristics. Thus, our data demonstrate
      reduced PPS due to an overall reduction of the first response as a form of
      modified PPS developing at old age.

PMID- 19745020
TI  - BDNF val66met polymorphism influences motor system function in the human brain.
AB  - Brain-derived neurotrophic factor (BDNF) is important to brain functions such as
      plasticity and repair. A single nucleotide polymorphism for this growth factor,
      val(66)met, is common and associated with decreased activity-dependent BDNF
      release. The current study evaluated the effects of this polymorphism in relation
      to human brain motor system function, short-term plasticity, and learning.
      Functional magnetic resonance imaging (fMRI) scanning during right index finger
      movement (n = 24) identified activation in a broad sensorimotor network. However,
      subjects with the polymorphism showed smaller activation volume within several
      brain regions as compared with subjects without the polymorphism. Repeat fMRI
      after 25 min of right index finger training found that the 2 genotype groups
      modulated brain activation differently. In several brain regions, subjects with
      the polymorphism showed greater activation volume reduction, whereas subjects
      without the polymorphism showed greater activation volume expansion. On a driving
      based motor learning task (independent cohort, n = 29), subjects with the
      polymorphism showed greater error during short-term learning and poorer retention
      over 4 days, relative to subjects without the polymorphism. The presence of this
      BDNF polymorphism is associated with differences in brain motor system function,
      altered short-term plasticity, and greater error in short-term motor learning.
      The broader implications of these findings are considered.

PMID- 19745021
TI  - Total exposure and exposure rate effects for alcohol and smoking and risk of head
      and neck cancer: a pooled analysis of case-control studies.
AB  - Although cigarette smoking and alcohol consumption increase risk for head and
      neck cancers, there have been few attempts to model risks quantitatively and to
      formally evaluate cancer site-specific risks. The authors pooled data from 15
      case-control studies and modeled the excess odds ratio (EOR) to assess risk by
      total exposure (pack-years and drink-years) and its modification by exposure rate
      (cigarettes/day and drinks/day). The smoking analysis included 1,761 laryngeal,
      2,453 pharyngeal, and 1,990 oral cavity cancers, and the alcohol analysis
      included 2,551 laryngeal, 3,693 pharyngeal, and 3,116 oval cavity cancers, with
      over 8,000 controls. Above 15 cigarettes/day, the EOR/pack-year decreased with
      increasing cigarettes/day, suggesting that greater cigarettes/day for a shorter
      duration was less deleterious than fewer cigarettes/day for a longer duration.
      Estimates of EOR/pack-year were homogeneous across sites, while the effects of
      cigarettes/day varied, indicating that the greater laryngeal cancer risk derived
      from differential cigarettes/day effects and not pack-years. EOR/drink-year
      estimates increased through 10 drinks/day, suggesting that greater drinks/day for
      a shorter duration was more deleterious than fewer drinks/day for a longer
      duration. Above 10 drinks/day, data were limited. EOR/drink-year estimates varied
      by site, while drinks/day effects were homogeneous, indicating that the greater
      pharyngeal/oral cavity cancer risk with alcohol consumption derived from the
      differential effects of drink-years and not drinks/day.

PMID- 19745023
TI  - Oxaliplatin-induced neurotoxicity: changes in axonal excitability precede
      development of neuropathy.
AB  - Administration of oxaliplatin, a platinum-based chemotherapy used extensively in
      the treatment of colorectal cancer, is complicated by prominent dose-limiting
      neurotoxicity. Acute neurotoxicity develops following oxaliplatin infusion and
      resolves within days, while chronic neuropathy develops progressively with higher
      cumulative doses. To investigate the pathophysiology of oxaliplatin-induced
      neurotoxicity and neuropathy, clinical grading scales, nerve conduction studies
      and a total of 905 axonal excitability studies were undertaken in a cohort of 58
      consecutive oxaliplatin-treated patients. Acutely following individual
      oxaliplatin infusions, significant changes were evident in both sensory and motor
      axons in recovery cycle parameters (P < 0.05), consistent with the development of
      a functional channelopathy of axonal sodium channels. Longitudinally across
      treatment (cumulative oxaliplatin dose 776 +/- 46 mg/m(2)), progressive
      abnormalities developed in sensory axons (refractoriness P < or = 0.001;
      superexcitability P < 0.001; hyperpolarizing threshold electrotonus 90-100 ms P <
      or = 0.001), while motor axonal excitability remained unchanged (P > 0.05),
      consistent with the purely sensory symptoms of chronic oxaliplatin-induced
      neuropathy. Sensory abnormalities occurred prior to significant reduction in
      compound sensory amplitude and the development of neuropathy (P < 0.01). Sensory
      excitability abnormalities that developed during early treatment cycles
      (cumulative dose 294 +/- 16 mg/m(2) oxaliplatin; P < 0.05) were able to predict
      final clinical outcome on an individual patient basis in 80% of patients. As
      such, sensory axonal excitability techniques may provide a means to identify pre
      clinical oxaliplatin-induced nerve dysfunction prior to the onset of chronic
      neuropathy. Furthermore, patients with severe neurotoxicity at treatment
      completion demonstrated greater excitability changes (P < 0.05) than those left
      with mild or moderate neurotoxicity, suggesting that assessment of sensory
      excitability parameters may provide a sensitive biomarker of severity for
      oxaliplatin-induced neurotoxicity.

PMID- 19745022
TI  - When top-down meets bottom-up: auditory training enhances verbal memory in
      schizophrenia.
AB  - A critical research priority for our field is to develop treatments that enhance
      cognitive functioning in schizophrenia and thereby attenuate the functional
      losses associated with the illness. In this article, we describe such a treatment
      method that is grounded in emerging research on the widespread sensory processing
      impairments of schizophrenia, as described elsewhere in this special issue. We
      first present the rationale for this treatment approach, which consists of
      cognitive training exercises that make use of principles derived from the past 2
      decades of basic science research in learning-induced neuroplasticity; these
      exercises explicitly target not only the higher order or "top-down" processes of
      cognition but also the content building blocks of accurate and efficient sensory
      representations to simultaneously achieve "bottom-up" remediation. We then
      summarize our experience to date and briefly review our behavioral and serum
      biomarker findings from a randomized controlled trial of this method in
      outpatients with long-term symptoms of schizophrenia. Finally, we present
      promising early psychophysiological evidence that supports the hypothesis that
      this cognitive training method induces changes in aspects of impaired bottom-up
      sensory processing in schizophrenia. We conclude with the observation that
      neuroplasticity-based cognitive training brings patients closer to physiological
      patterns seen in healthy participants, suggesting that it changes the brain in an
      adaptive manner in schizophrenia.

PMID- 19745024
TI  - Spatial characterization of interictal high frequency oscillations in epileptic
      neocortex.
AB  - Interictal high frequency oscillations (HFOs), in particular those with frequency
      components in excess of 200 Hz, have been proposed as important biomarkers of
      epileptic cortex as well as the genesis of seizures. We investigated the spatial
      extent, classification and distribution of HFOs using a dense 4 x 4 mm(2) two
      dimensional microelectrode array implanted in the neocortex of four patients
      undergoing epilepsy surgery. The majority (97%) of oscillations detected included
      fast ripples and were concentrated in relatively few recording sites. While most
      HFOs were limited to single channels, approximately 10% occurred on a larger
      spatial scale with simultaneous but morphologically distinct detections in
      multiple channels. Eighty per cent of these large-scale events were associated
      with interictal epileptiform discharges. We propose that large-scale HFOs, rather
      than the more frequent highly focal events, are the substrates of the HFOs
      detected by clinical depth electrodes. This feature was prominent in three
      patients but rarely seen in only one patient recorded outside epileptogenic
      cortex. Additionally, we found that HFOs were commonly associated with widespread
      interictal epileptiform discharges but not with locally generated
      'microdischarges'. Our observations raise the possibility that, rather than being
      initiators of epileptiform activity, fast ripples may be markers of a secondary
      local response.

PMID- 19745025
TI  - A conceptual model of optimal international service-learning and its application
      to global health initiatives in rehabilitation.
AB  - BACKGROUND: There is growing involvement by US clinicians, faculty members, and
      students in global health initiatives, including international service-learning
      (ISL). Limited research has been done to examine the profession's increasing
      global engagement, or the ISL phenomenon in particular, and no research has been
      done to determine best practices. This study was intended as an early step in the
      examination of the physical therapy profession's role and activities in the
      global health arena within and beyond academics. OBJECTIVES: The purposes of this
      study were: (1) to identify and analyze the common structures and processes among
      established ISL programs within physical therapist education programs and (2) to
      develop a conceptual model of optimal ISL within physical therapist education
      programs. DESIGN: A descriptive, exploratory study was completed using grounded
      theory. METHODS: Telephone interviews were completed with 14 faculty members who
      had been involved in international service, international learning, or ISL in
      physical therapist education programs. Interviews were transcribed, and
      transcriptions were analyzed using the grounded theory method. RESULTS: Four
      major themes emerged from the data: structure, reciprocity, relationship, and
      sustainability. A conceptual model of and a proposed definition for optimal ISL
      in physical therapist education were developed. Seven essential components of the
      conceptual model are: a partner that understands the role of physical therapy,
      community-identified needs, explicit service and learning objectives, reflection,
      preparation, risk management, and service and learning outcome measures.
      Essential consequences are positive effects on students and community.
      CONCLUSIONS: The conceptual model and definition of optimal ISL can be used to
      direct development of new ISL programs and to improve existing programs. In
      addition, they can offer substantive guidance to any physical therapist involved
      in global health initiatives.

PMID- 19745026
TI  - The Patient Goal Priority Questionnaire is moderately reproducible in people with
      persistent musculoskeletal pain.
AB  - BACKGROUND: The Patient Goal Priority Questionnaire (PGPQ) is a patient-specific
      measure for identification of behavioral goals and evaluation of clinically
      significant changes. The use of such a measure in clinical settings and research
      requires that identified goals be consistent over time. Self-reports of behaviors
      related to the goals should be reliably estimated. OBJECTIVE: The purpose of this
      study was to estimate chance-corrected agreement and test-retest reliability of
      the PGPQ. Chance-corrected agreement between the PGPQ and a similar therapist
      guided goal identification tool, the Patient Goal Priority List (PGPL), also was
      estimated. DESIGN: A correlative and prospective design with 3 measurement points
      (M1, M2, and M3) was used in the study. METHODS: Fifty-four people who consulted
      physical therapists in primary care for persistent musculoskeletal pain were
      included in the study. Analyses of chance-corrected agreement and test-retest
      reliability of the PGPQ were done at M1 and M2. Chance-corrected agreement
      between procedures (PGPQ and PGPL) also was analyzed at M1 and M3. RESULTS: The
      percentage of agreement on content of the priority lists of the PGPQ at M1 and M2
      was 52%. Cohen kappa values for agreement of rankings ranged between .47 and .64.
      Test-retest reliability coefficients for the self-report scales of the PGPQ
      ranged from .35 to .81. Chance-corrected agreement decreased when physical
      therapists were involved in the goal identification process using the PGPL (kappa
      = .08-.46). LIMITATIONS: Varying item content and a small, heterogeneous sample
      possibly increased variation and the standard error of measurements. The
      feasibility of using traditional approaches to psychometric evaluation of patient
      specific measures is questionable. CONCLUSIONS: Chance-corrected agreement and
      test-retest reliability of the PGPQ were moderate. Involving a physical therapist
      in the goal identification procedure possibly introduced further bias. The size
      of the measurement error must be taken into account when using the PGPQ for
      estimations of clinically important changes.

PMID- 19745027
TI  - Quantitative miRNA expression analysis: comparing microarrays with next
      generation sequencing.
AB  - Recently, next-generation sequencing has been introduced as a promising, new
      platform for assessing the copy number of transcripts, while the existing
      microarray technology is considered less reliable for absolute, quantitative
      expression measurements. Nonetheless, so far, results from the two technologies
      have only been compared based on biological data, leading to the conclusion that,
      although they are somewhat correlated, expression values differ significantly.
      Here, we use synthetic RNA samples, resembling human microRNA samples, to find
      that microarray expression measures actually correlate better with sample RNA
      content than expression measures obtained from sequencing data. In addition,
      microarrays appear highly sensitive and perform equivalently to next-generation
      sequencing in terms of reproducibility and relative ratio quantification.

PMID- 19745028
TI  - An analysis of MRI and ultrasound imaging in patients with gout who have normal
      plain radiographs.
AB  - OBJECTIVE: The aim of this study was to analyse the prevalence of occult
      destructive arthropathy in subjects with gout and normal plain radiographs by
      utilizing MRI and ultrasound (US). METHODS: The study consisted of two visits. At
      Visit 1, a plain radiograph of the 'index joint' was obtained. The 'index joint'
      was defined as a joint that has had the most acute attacks of gout historically.
      The index joint plain radiograph had to be free of erosive damage in order for
      the subject to qualify for Visit 2. At Visit 2, the subject had an MRI with
      contrast and an US of the index joint. Each subject also had an MRI and US of an
      'asymptomatic joint'. The 'asymptomatic joint' was defined as a joint that had
      never experienced an acute attack of gout (determined by standard protocol). The
      primary endpoint was erosive changes on the MRI and/or US of the index joint.
      Secondary endpoints included erosive changes on the asymptomatic joint as well as
      bone marrow oedema (BME) (on MRI), synovial pannus (SP), soft tissue tophi (STT)
      or oedema (STE) on either the index or asymptomatic joint. RESULTS: Twenty-seven
      subjects (26 males; 1 female) completed both visits. Their average age and
      disease duration were 55.1 years (range 21-75 years) and 6.8 years (range 0.25-25
      years), respectively. The subjects' average serum uric acid level over the past 5
      years was 8.09 mg/dl (range 4.1-12.8 mg/dl); their average on the day of Visit 1
      was 7.96 mg/dl (range 4.6-13.9 mg/dl). The first MTP was the most common index
      joint (17) followed by the ankle (5), mid-tarsal (2), knee (2) and wrist (1). The
      knee was the most common asymptomatic joint (21) followed by the wrist (3), MTP
      (2) and ankle (1). All subjects had both MRIs; one subject refused the US. Out of
      27 subjects, 15 (56%) had erosions on MRI of their index joint (P < 0.0001); only
      1 subject (4%) had erosions identified in the index joint by US (P = NS).
      Regarding the secondary endpoints on the index joint, the MRI detected SP (13),
      BME (4), STE (3) and STT (0); the US detected SP (1), STT (1) and STE (0).
      Regarding the MRI of the asymptomatic joint, positive findings included SP (3),
      BME (3), STE (2) and erosions (1). There were no positive findings by US in the
      asymptomatic joint. CONCLUSIONS: A large percentage of patients with gout and
      normal plain radiographs have occult destructive arthropathy that is only
      detected by advanced imaging such as MRI and/or US. However, MRI appears to be
      much more sensitive than US at detecting these findings.

PMID- 19745029
TI  - Role of deleted in colon carcinoma in osteoarthritis and in chondrocyte
      migration.
AB  - OBJECTIVE: The concept of the chondrocyte as a stationary cell surrounded by an
      apparently impenetrable matrix has been challenged by in vitro observations in
      recent years. Chondrocyte migration may have a role in remodelling of the
      cartilage and pathological conditions. Candidate molecules are repellent factors
      for the regulation of chondrocyte migration, which are expressed in fetal and
      adult cartilage. We analysed the potential role of the receptor deleted in colon
      carcinoma (DCC) in chondrocytes, as this may exert attractive activities.
      METHODS: Gene expression was determined by quantitative RT-PCR and
      immunohistochemistry, and gene regulation by electro mobility shift assay and
      chromatin immunoprecipitation. Functional assays on migration and differentiation
      were done after cell treatment and transfection. RESULTS: DCC was shown to be
      specifically up-regulated in OA compared with normal chondrocytes in vitro and in
      vivo. Promoter analysis and transfection studies showed that the up-regulation of
      DCC in OA chondrocytes may be mediated by the transcription factors Sox9 and AP
      2. Netrin-1, the ligand of DCC, was revealed to induce the migration of OA
      chondrocytes specifically. Expression of DCC in healthy chondrocytes by transient
      transfection significantly induced cell migration and chemotaxis to Netrin-1. DCC
      expression had no influence on cell differentiation; however, induction of MMP1
      and -3 expression was observed. CONCLUSION: Strong differential expression of DCC
      in OA compared with normal chondrocytes hints of a possible role of DCC in the
      pathophysiology of OA. The strong impact of the DCC receptor on cellular mobility
      of chondrocytes in vitro suggests a major relevance of migratory activities in
      physiological and pathological conditions of cartilage. However, definite proof
      of chondrocyte movements in vivo still has to be established.

PMID- 19745030
TI  - Molecular emm genotyping and antibiotic susceptibility of Streptococcus
      dysgalactiae subsp. equisimilis isolated from invasive and non-invasive
      infections.
AB  - To analyse the characteristics of infections caused by Streptococcus dysgalactiae
      subsp. equisimilis, clinical isolates (n=145) were collected at 11 medical
      institutions between September 2003 and October 2005. These isolates belonged to
      Lancefield group A (n=5), group C (n=18) or group G (n=122). Among all isolates,
      42 strains were isolated from sterile samples such as blood, synovial fluid and
      tissue specimens from patients who were mostly over 50 years with invasive
      infections, and included seven cases of streptococcal toxic shock syndrome and
      necrotizing fasciitis. In contrast, the remaining 103 were isolated mainly from
      patients of all age groups with non-invasive infections such as
      pharyngotonsillitis. These isolates were classified into 25 types based on emm
      genotyping. A significant difference in emm types was observed between isolates
      from invasive and non-invasive infections (P<0.001): stG485, stG6792 and stG2078
      predominated among isolates from invasive infections. A phylogenetic tree of
      complete open reading frames of emm genes in this organism showed high homology
      with those of Streptococcus pyogenes, but not with those of other streptococci.
      The presence of five different clones was estimated based on DNA profiles of
      isolates from invasive infections obtained by PFGE. Genes for resistance to
      macrolides [erm(A), three isolates; erm(B), five isolates; mef(A), seven
      isolates] and levofloxacin (mutations in gyrA and parC, four isolates) were
      identified in this organism. These results suggest the need for further
      nationwide surveillance of invasive infections caused by S. dysgalactiae subsp.
      equisimilis.

PMID- 19745031
TI  - Zoonotic transmission of Streptococcus equi subsp. zooepidemicus from a dog to a
      handler.
AB  - This is, to the best of our knowledge, the first case report to describe the
      apparent transmission of Streptococcus equi subsp. zooepidemicus from an infected
      dog to a handler who subsequently developed severe systemic infection.
      Characterization of the haemolytic streptococci isolated from both the patient
      and the dog, by phenotypic and molecular analysis, confirmed the canine and human
      isolates were identical.

PMID- 19745032
TI  - Development of ertapenem resistance in a patient with mediastinitis caused by
      Klebsiella pneumoniae producing an extended-spectrum beta-lactamase.
AB  - The aim was to study the clinical and microbiological features associated with a
      carbapenem-resistant Klebsiella pneumoniae isolate that had been selected in vivo
      by an ertapenem-containing regimen in a patient with mediastinitis despite high
      blood and mediastinal levels of ertapenem. Carbapenem resistance was
      characterized by conjugation, PCR, DNA sequencing and analysis of outer-membrane
      proteins. The isolates susceptible and resistant to the carbapenems were compared
      by ribotyping and PFGE. Resistance to all available beta-lactams was most
      probably due to combined production of extended-spectrum beta-lactamase (ESBL)
      CTX-M-15 and loss of OmpK36 porin. The results of ribotyping and PFGE suggest
      that the carbapenem-resistant strain was a derivative of the original mediastinal
      isolate rather than a superinfecting isolate. This observation stresses the risk
      of selection of pan-penem resistant strains of enterobacteria when ertapenem is
      used for the treatment of severe infections due to ESBL-producing enterobacteria.

PMID- 19745034
TI  - Toxic megacolon complicating a Clostridium difficile infection in a pregnant
      woman.
AB  - Clostridium difficile infection (CDI) in non-hospitalized patients has been
      reported with increased frequency, whereas an association between CDI and
      pregnancy has not been highlighted. We report a case of toxic megacolon
      complicating a severe CDI during the second trimester of pregnancy in a patient
      without traditional risk factors, such as antibiotic use, immunodeficiency, and
      prolonged and recent hospitalization.

PMID- 19745033
TI  - Identification of virulence determinants of Mycobacterium avium that impact on
      the ability to resist host killing mechanisms.
AB  - Mycobacterium avium is an opportunistic pathogen associated with pulmonary
      disease in non-AIDS patients and disseminated infection in patients with AIDS.
      The chief route of infection is by colonization and invasion of the mucosa of the
      gastrointestinal tract, but infection through the respiratory route also occurs.
      After crossing the mucosa, M. avium infects and replicates within tissue
      macrophages. To identify M. avium genes required for survival in vivo, a library
      of signature-tagged transposon mutants was constructed and screened for clones
      attenuated in mice. Thirty-two clones were found to be attenuated for their
      virulence, from which eleven were sequenced and tested further. All the mutants
      studied grew similarly in vitro to the wild-type MAC104. Ten mutants were tested
      individually in mice, confirming the attenuated phenotype. MAV_2450, a polyketide
      synthase homologue to Mycobacterium tuberculosis pks12, was identified. STM5 and
      STM10 genes (encoding two hypothetical proteins MAV_4292 and MAV_4012) were
      associated with susceptibility to oxidative products. Mutants MAV_2450, MAV_4292,
      MAV_0385 and MAV_4264 live in macrophage vacuoles with acidic pH (below 6.9).
      Mutants MAV_4292, MAV_0385 and MAV_4264 were susceptible to nitric oxide in
      vitro. The study of individual mutants can potentially lead to new knowledge
      about M. avium pathogenic mechanisms.

PMID- 19745035
TI  - Alterations to the structure of Leishmania major induced by N-arylisoquinolines
      correlate with compound accumulation and disposition.
AB  - Naphthylisoquinoline alkaloids equipped with a N,C-hetero-'biaryl' axis, and, in
      particular, simplified synthetic analogues thereof, kill intracellular Leishmania
      major at concentrations in the low submicromolar range, while being significantly
      less toxic to their major host cell, the macrophage, at the same concentrations.
      To further investigate their mechanism of action we evaluated the morphological
      and ultrastructural changes induced by specific N-arylisoquinolines in L. major,
      and the correlation of these changes with compound accumulation and disposition
      by the parasite. After 24 h of treatment with the synthetic arylisoquinolinium
      salts 3 or 4, dramatic structural changes and cell death were observed.
      Furthermore, the auto-fluorescent derivative salt 3 accumulates continually in
      intracellular compartments. Our results thus suggest that the leishmanicidal
      effect of arylisoquinolinium salts may involve their ability to accumulate and
      precipitate in intracellular organelles, form a huge vacuole and eventually
      promote cell lysis.

PMID- 19745036
TI  - Daptomycin is not active against rapidly growing mycobacteria.

PMID- 19745037
TI  - Role of insulin as a negative regulator of plasma endocannabinoid levels in obese
      and nonobese subjects.
AB  - OBJECTIVE: Endocannabinoids (ECs) control metabolism via cannabinoid receptors
      type 1 (CB1). Their plasma levels are elevated in overweight type 2 diabetes
      (T2D) and in obese patients, and decrease postprandially in normoweight
      individuals. We investigated in two different cohorts of nonobese or obese
      volunteers whether oral glucose in glucose tolerance tests (OGTT) or acute
      insulin infusion during euglycemic hyperinsulinemic clamp affect plasma EC
      levels. DESIGN AND METHODS: OGTT was performed in ten obese hyperinsulinemic
      patients (body mass index (BMI)=35.8 kg/m2, fasting insulin=14.83 mU/l), and ten
      normoweight normoinsulinemic volunteers (BMI=21.9 kg/m2, fasting insulin=7.2
      mU/l). Insulin clamp was performed in 19 mostly nonobese men (BMI=25.8 kg/m2)
      with varying degrees of liver fat and plasma triglycerides (TGs), with (n=7) or
      without T2D. Plasma levels of ECs (anandamide and 2-arachidonoylglycerol (2-AG))
      were measured by liquid chromatography-mass spectrometry, before and 60 and 180
      min after OGTT, and before and 240 and 480 min after insulin or saline infusion.
      RESULTS: Oral glucose load decreased anandamide plasma levels to an extent
      inversely correlated with BMI, waist circumference, subcutaneous fat, fasting
      insulin and total glucose, and insulin areas under the curve during the OGTT, and
      nonsignificantly in obese volunteers. Insulin infusion decreased anandamide
      levels to an extent that weakly, but significantly, correlated negatively with
      TGs, liver fat and fasting insulin, and positively with high density lipoprotein
      cholesterol. OGTT decreased 2-AG levels to a lower extent and in a way weakly
      inversely correlated with fasting insulin. CONCLUSIONS: We suggest that insulin
      reduces EC levels in a way inversely related to anthropometric and metabolic
      predictors of insulin resistance and dyslipidemia.

PMID- 19745038
TI  - Association of classroom participation and examination performance in a first
      year medical school course.
AB  - The advent of internet-based delivery of basic medical science lectures may
      unintentionally lead to decreased classroom attendance and participation, thereby
      creating a distance learning paradigm. In this study, we tested the hypothesis
      that classroom attendance/participation may be positively correlated with
      performance on a written examination for first-year medical school instruction.
      The study subjects consisted of 115 first-year medical students. The introductory
      respiratory structure-function instruction was designed to include one
      noncompulsory pretest, four short postinstruction noncompulsory self-evaluation
      tests that were unannounced as to date and time, and one compulsory comprehensive
      examination. The relationship between attendance/participation, measured by the
      number of noncompulsory tests taken, and performance on the comprehensive
      examination was determined by Pearson's correlation coefficient, one-way ANOVA,
      and a chi(2)-test of significance. The average score on the pretest was 28%; for
      the same items on the comprehensive examination (posttest), the average score was
      73%. For the 80 students who took the pretest, this translated to an overall
      score increase of 161%. Attendance/participation in four or five of the
      noncompulsory tests resulted in an 83.3% pass rate on the comprehensive exam
      compared with a rate of 52.9% for attendance/participation in three, two, one, or
      none of the five noncompulsory tests; the overall pass rate was 60.9%. There was
      a significant association between a high rate of classroom
      attendance/participation and a high score on the comprehensive examination
      (Pearson's chi(2) = 8.599, P < 0.01). These findings suggest that classroom
      attendance/participation may be a significant determinant of performance of
      medical students on comprehensive examinations in first-year basic medical
      science courses. It is concluded that a substantial number of first-year medical
      students in this study could be at risk for poor performance because they may
      believe that there is an equivalency between internet- and classroom-based
      instruction in basic medical science courses.

PMID- 19745039
TI  - Standing on the shoulders of giants: Dean Franklin and his remarkable
      contributions to physiological measurements in animals.
AB  - The use of electronic instrumentation to monitor physiological function in
      conscious research animals and humans has become routine. Beyond basic research,
      animal studies using these methods are required by government regulatory agencies
      worldwide before human testing of potential new drugs. Living, as we do, in an
      age of miniaturized high-tech electronic devices, we are accustomed to believing
      this technology is easy; however, this has not always been the case. While a
      broad supporting cast of engineers, physiologists, fellows, and technicians was
      involved, the true innovators were Dr. Robert Rushmer, Dr. Robert Van Citters,
      and Mr. Dean Franklin. Before Dean Franklin's death in 2007, the primary author
      recorded approximately 5 h of interviews with him at his home in Columbia, MO. An
      additional approximate 1.5-h interview was recorded with Dr. Van Citters via
      telephone. The information contained herein is based on the recollections of
      these men as recorded in their interviews.

PMID- 19745040
TI  - A forgotten moment in physiology: the Lovelace Woman in Space Program (1960
      1962).
AB  - In 1959, Brigadier General Donald Flickinger and Dr. W. Randolph Lovelace II
      suggested that it would be more practical from an engineering standpoint to send
      women rather than men into space due to their lower body weights and oxygen
      requirements. When the Air Force decided not to pursue this project, Dr. Lovelace
      assumed leadership of the Woman in Space Program and began medical and
      physiological testing of a series of accomplished women aviators at the Lovelace
      Medical Clinic in Albuquerque, NM, in 1960. The tests that these women underwent
      were identical to those used to test the original Mercury astronauts, with the
      addition of gynecological examinations. Thirteen of the nineteen women tested
      passed these strenuous physiological exams (for comparison, 18 of 32 men tested
      passed); a subset of these pilots was further tested on a series of psychological
      exams that were similar to or, in some instances, more demanding than those given
      to male Mercury candidates. Despite these promising results, further testing was
      halted, and the Woman in Space Program was disbanded in 1962. Although the Woman
      in Space Program received a great deal of publicity at the time, the story of
      these women was somewhat lost until they were reunited at the 1999 launch of the
      shuttle Columbia, commanded by Colonel Eileen Collins.

PMID- 19745041
TI  - Teaching the role of secretin in the regulation of gastric acid secretion using a
      classic paper by Johnson and Grossman.
AB  - The regulation of gastric acid secretion has been the subject of investigation
      for over a century. Inhibition of gastrin-induced acid secretion by the intestine
      derived hormone secretin provides a classic physiological example of negative
      feedback in the gastrointestinal tract. A classic paper by Leonard R. Johnson and
      Morton I. Grossman clearly shows the ability of secretin to negatively regulate
      gastric acid secretion, providing students with an example of this feedback loop.
      In addition, this article demonstrates the step forward in gastrointestinal
      endocrinology that occurred when pure preparations of secretin and other
      gastrointestinal hormones first became available. The comparison of the effects
      of exogenous, purified secretin to the physiological stimulus of acid in the
      duodenum is an important example of how newly available reagents allow scientists
      such as Johnson and Grossman to clarify the mechanisms behind previously
      established processes. One or more figures from this classic paper can be used to
      give students insight into the role of secretin in the regulation of the function
      of the gastrointestinal tract and will also give students a clear example of how
      the careful experimentation and clear interest in gastrointestinal physiology led
      Johnson and Grossman to advance the field.

PMID- 19745042
TI  - Teaching the modes of Ca2+ transport between the plasma membrane and endoplasmic
      reticulum using a classic paper by Kwan et al.
AB  - This teaching article uses the report by Kwan et al., "Effects of methacholine,
      thapsigargin, and La(3+) on plasmalemmal and intracellular Ca(2+) transport in
      lacrimal acinar cells," where the effects of Ca(2+)-mobilizing agents in
      regulating Ca(2+) fluxes were examined under various conditions. Upper-level
      undergraduate and new graduate students in physiology are the targe audience.
      Teaching and learning points are put forth in this article to illustrate 1) the
      characteristics of methacholine- and thapsigargin-induced Ca(2+) responses, 2)
      the different endoplasmic reticulum Ca(2+) stores accessible to methacholine and
      thapsigargin, 3) the inhibitory effects of La(3+) on Ca(2+) extrusion and Ca(2+)
      influx, and 4) the facilitatory role of La(3+) on endoplasmic reticulum Ca(2+)
      recycling. Each of the above concepts is first explained with references to the
      figures adapted from the original article. A list of student learning questions
      then follows, where the answers are found in the teaching notes for the
      instructors. It is the objective of this article to make both teaching and
      learning Ca(2+) regulation a rewarding experience for all.

PMID- 19745043
TI  - Unifying concepts in stimulus-secretion coupling in endocrine cells and some
      implications for therapeutics.
AB  - Stimulus-secretion coupling (SSC) in endocrine cells remains underappreciated as
      a subject for the study/teaching of general physiology. In the present article,
      we review key new electrophysiological, electrochemical, and fluorescence optical
      techniques for the study of exocytosis in single cells that have made this a
      fertile area for recent research. Based on findings using these techniques, we
      developed a model of SSC for adrenal chromaffin cells that blends features of
      Ca(2+) entry-dependent SSC (characteristic of neurons) with G protein receptor
      coupled, Ca(2+) release-dependent, and second messenger-dependent SSC
      (characteristic of epithelial exocrine cells and nucleated blood cells). This
      model requires two distinct pools of secretory graunules with differing Ca(2+)
      sensitivities. We extended this model to account for SSC in a wide variety of
      peripheral and hypothalamic/pituitary-based endocrine cells. These include
      osmosensitive magnocellular neurosecretory cells releasing antidiuretic hormone,
      stretch-sensitive atrial myocytes secreting atrial natriuretic peptide, K(+)
      sensitive adrenal glomerulosa cells secreting aldosterone, Ca(2+)-sensitive
      parathyroid chief cells secreting parathyroid hormone, and glucose-sensitive beta
      and alpha-cells of pancreatic islets secreting insulin and glucagon,
      respectively. We conclude this article with implications of this approach for
      pathophysiology and therapeutics, including defects in chief cell Ca(2+)
      sensitivity, resulting in the hyperparathyroidism of renal disease, and defects
      in biphasic insulin secretion, resulting in diabetes mellitus.

PMID- 19745044
TI  - What makes the learning of physiology in a PBL medical curriculum challenging?
      Student perceptions.
AB  - Physiology is an integral component of any medical curriculum. Traditionally, the
      learning of physiology has relied heavily on systems-based didactic lectures. In
      2001, the Nelson R. Mandela School of Medicine (NRMSM; Durban, South Africa)
      embarked on a problem-based curriculum in which the learning of physiology was
      integrated with relevant clinical scenarios. Students are expected to gain an
      understanding of physiology through self-directed research with only certain
      aspects being covered in large-group resource sessions (LGRSs). It has gradually
      become evident that this approach has resulted in significant gaps in students'
      understanding of basic physiological concepts. A survey of student perceptions of
      needs for physiology was undertaken to gain a better understanding of their
      perceived problems and also to inform them of proposed curricular changes.
      Students were asked to what extent they thought physiology was essential for
      their understanding of pathology, interpretation of patients' clinical signs and
      presentation of symptoms, and analysis of laboratory results. Students were also
      invited to detail the difficulties they experienced in understanding in LGRSs on
      clinical and physiological topics. The results of the survey indicate that
      greater interaction of students with experts is needed. In particular, students
      felt that they lacked the basic conceptual foundations essential for the learning
      and understanding of physiology, since the difficulties that the students
      identified are mainly terminological and conceptual in nature.

PMID- 19745045
TI  - The situational interest of undergraduate students in zoophysiology.
AB  - Situational interest has been identified as an important motivational variable
      that has an impact on students' academic performances, yet little is known about
      how the specific variable of the learning environment might trigger students'
      situational interest. The purpose of this study was to investigate sources that
      stimulate the interest of students in an undergraduate course in zoophysiology.
      Observations, informal conversational interviews, and responses to a survey were
      used to identify sources of interest. Five situational variables and one
      predominantly individual variable are documented to influence the catching of
      interest of students. The situational variables are live animals, "Ah-ha!"
      experiences, meaningfulness, social involvement, and humor, whereas the
      predominantly individual variable is background knowledge. We conclude that the
      situational variables are largely under the control of the faculty and should be
      considered when planning instruction. By focusing on the enhancement of
      situational interest in physiology lessons, faculty members can find ways to
      foster students' involvement in specific content areas and increase levels of
      academic motivation.

PMID- 19745046
TI  - A simulation for teaching the basic and clinical science of fluid therapy.
AB  - The course "Management of Fluid and Electrolyte Disorders" is an applied
      physiology course taught using lectures and paper-based cases. The course
      approaches fluid therapy from both basic science and clinical perspectives. While
      paper cases provide a basis for application of basic science concepts, they lack
      key components of genuine clinical cases that, by nature, are diverse, change
      over time, and respond in unique ways to therapeutic interventions. We developed
      a dynamic model using STELLA software that simulates normal and abnormal fluid
      and electrolyte balance in the dog. Students interact, not with the underlying
      model, but with a user interface that provides sufficient data (skin turgor,
      chemistry panel, etc.) for the clinical assessment of patients and an opportunity
      for treatment. Students administer fluids and supplements, and the model responds
      in "real time," requiring regular reassessment and, potentially, adaptation of
      the treatment strategy. The level of success is determined by clinical outcome,
      including improvement, deterioration, or death. We expected that the simulated
      cases could be used to teach both the clinical and basic science of fluid
      therapy. The simulation provides exposure to a realistic clinical environment,
      and students tend to focus on this aspect of the simulation while, for the most
      part, ignoring an exploration of the underlying physiological basis for patient
      responses. We discuss how the instructor's expertise can provide sufficient
      support, feedback, and scaffolding so that students can extract maximum
      understanding of the basic science in the context of assessing and treating at
      the clinical level.

PMID- 19745047
TI  - Blood glucose monitoring as a teaching tool for endocrinology: a new perspective.
AB  - The education of new allied health professionals and nurses in proper endocrine
      evaluation and care has become critical in recent years, especially considering
      the greatly increased prevalence of diabetes in adults and children. The
      evaluation of blood glucose levels in human volunteers over time is a powerful
      teaching tool for endocrinology that has the added benefit of exposing the
      student to the most fundamental task in diabetes management. The classic
      procedure involving the ingestion of sucrose followed by blood glucose monitoring
      was used here to teach the concepts of nonhormonal control of hormone release and
      blood glucose homeostasis. In addition, a number of volunteers did not ingest a
      sucrose solution but merely held it in their mouths and expectorated. This so
      called "spit" technique has been successfully used to induce the cephalic phase
      of insulin release (CPIR), an example of neural control of hormone release. As
      expected, volunteers who ingested sucrose displayed a 38.5% increase in blood
      glucose 20 min postingestion and a concomitant decrease in blood glucose to near
      baseline by 60 min postingestion. Those volunteers who did not ingest the sucrose
      solution displayed a 12.9% reduction in blood glucose levels by 40 min
      postcompletion, suggestive of the CPIR, followed by a gradual increase in blood
      glucose levels to near baseline by 60 min postcompletion. The addition of the
      "spit" technique to this revised protocol of the evaluation of blood glucose
      exposes the student to the neural control of hormone release and a second example
      of energy homeostasis.

PMID- 19745048
TI  - The physiology and mechanics of undulatory swimming: a student laboratory
      exercise using medicinal leeches.
AB  - The medicinal leech is a useful animal model for investigating undulatory
      swimming in the classroom. Unlike many swimming organisms, its swimming
      performance can be quantified without specialized equipment. A large blood meal
      alters swimming behavior in a way that can be used to generate a discussion of
      the hydrodynamics of swimming, muscle mechanics, hydrostatic skeletons, and the
      physiological features that allow leeches to deal with the volume increase and
      osmotic load imposed by the meal. Analyses can be carried out at a range of
      levels tailored to suit a particular class.

PMID- 19745049
TI  - Cardiac structure and function in humans: a new cardiovascular physiology
      laboratory.
AB  - As the traditional cardiovascular control laboratory has disappeared from the
      first-year medical school curriculum, we have recognized the need to develop
      another "hands-on" experience as a vehicle for wide-ranging discussions of
      cardiovascular control mechanisms. Using an echocardiograph, an automatic blood
      pressure cuff, and a reclining bicycle, we developed protocols to illustrate the
      changes in cardiac and vascular function that occur with changes in posture,
      venous return, and graded exercise. We use medical student volunteers and a
      professional echocardiographer to generate and acquire data, respectively. In
      small-group sessions, we developed an interactive approach to discuss the data
      and to make a large number of calculations from a limited number of measurements.
      The sequence of cardiac events and cardiac structure in vivo were illustrated
      with the volunteers lying down, standing, and then with their legs raised
      passively above the heart to increase venous return. Volunteers were then asked
      to peddle the bicycle to achieve steady-state heart rates of 110 and 150
      beats/min. Data were collected in all these states, and calculations were
      performed and used as the basis of a small-group discussion to illustrate
      physiological principles. Information related to a surprisingly large number of
      cardiovascular control mechanisms was derived, and its relevance to
      cardiovascular dysfunction was explored. This communication describes our
      experience in developing a new cardiovascular control laboratory to reinforce
      didactic material presented in lectures and small-group sessions.

PMID- 19745050
TI  - Changes of membrane potential demonstrated by changes in solution color.

PMID- 19745051
TI  - Does GI physiology support the rationale behind switching from oral rehydration
      solution to intravenous saline preparations in the management of children with
      acute severe diarrhea?

PMID- 19745053
TI  - MeCP2/H3meK9 are involved in IL-6 gene silencing in pancreatic adenocarcinoma
      cell lines.
AB  - The aim of the present study was to analyse the molecular mechanisms involved in
      the Interleukin-6 (IL-6) silencing in pancreatic adenocarcinoma cell lines. Our
      results demonstrate that TNF-alpha, a major IL-6 inducer, is able to induce IL-6
      only in three out of six cell lines examined. 5-aza-2'-deoxycytidine (DAC), but
      not trichostatin A (TSA), activates the expression of IL-6 in all cell lines,
      indicating that DNA methylation, but not histone deacetylation, plays an
      essential role in IL-6 silencing. Indeed, the IL-6 upstream region shows a
      methylation status that correlates with IL-6 expression and binds MeCP2 and
      H3meK9 only in the non-expressing cell lines. Our results suggest that critical
      methylations located from positions -666 to -426 relative to the transcription
      start site of IL-6 may act as binding sites for MeCP2.

PMID- 19745052
TI  - Functional significance of the Rad51-Srs2 complex in Rad51 presynaptic filament
      disruption.
AB  - The SRS2 (Suppressor of RAD Six screen mutant 2) gene encodes an ATP-dependent
      DNA helicase that regulates homologous recombination in Saccharomyces cerevisiae.
      Mutations in SRS2 result in a hyper-recombination phenotype, sensitivity to DNA
      damaging agents and synthetic lethality with mutations that affect DNA
      metabolism. Several of these phenotypes can be suppressed by inactivating genes
      of the RAD52 epistasis group that promote homologous recombination, implicating
      inappropriate recombination as the underlying cause of the mutant phenotype.
      Consistent with the genetic data, purified Srs2 strongly inhibits Rad51-mediated
      recombination reactions by disrupting the Rad51-ssDNA presynaptic filament. Srs2
      interacts with Rad51 in the yeast two-hybrid assay and also in vitro. To
      investigate the functional relevance of the Srs2-Rad51 complex, we have generated
      srs2 truncation mutants that retain full ATPase and helicase activities, but
      differ in their ability to interact with Rad51. Importantly, the srs2 mutant
      proteins attenuated for Rad51 interaction are much less capable of Rad51
      presynaptic filament disruption. An internal deletion in Srs2 likewise diminishes
      Rad51 interaction and anti-recombinase activity. We also present evidence that
      deleting the Srs2 C-terminus engenders a hyper-recombination phenotype. These
      results highlight the importance of Rad51 interaction in the anti-recombinase
      function of Srs2, and provide evidence that this Srs2 function can be uncoupled
      from its helicase activity.

PMID- 19745054
TI  - Selection for minimization of translational frameshifting errors as a factor in
      the evolution of codon usage.
AB  - In a wide range of genomes, it was observed that the usage of synonymous codons
      is biased toward specific codons and codon patterns. Factors that are implicated
      in the selection for codon usage include facilitation of fast and accurate
      translation. There are two types of translational errors: missense errors and
      processivity errors. There is considerable evidence in support of the hypothesis
      that codon usage is optimized to minimize missense errors. In contrast, little is
      known about the relationship between codon usage and frameshifting errors, an
      important form of processivity errors, which appear to occur at frequencies
      comparable to the frequencies of missense errors. Based on the recently proposed
      pause-and-slip model of frameshifting, we developed Frameshifting Robustness
      Score (FRS). We used this measure to test if the pattern of codon usage indicates
      optimization against frameshifting errors. We found that the FRS values of
      protein-coding sequences from four analyzed genomes (the bacteria Bacillus
      subtilis and Escherichia coli, and the yeasts Saccharomyces cerevisiae and
      Schizosaccharomyce pombe) were typically higher than expected by chance. Other
      properties of FRS patterns observed in B. subtilis, S. cerevisiae and S. pombe,
      such as the tendency of FRS to increase from the 5'- to 3'-end of protein-coding
      sequences, were also consistent with the hypothesis of optimization against
      frameshifting errors in translation. For E. coli, the results of different tests
      were less consistent, suggestive of a much weaker optimization, if any.
      Collectively, the results fit the concept of selection against mistranslation
      induced protein misfolding being one of the factors shaping the evolution of both
      coding and non-coding sequences.

PMID- 19745055
TI  - Genome-wide analysis of a G-quadruplex-specific single-chain antibody that
      regulates gene expression.
AB  - G-quadruplex nucleic acids have been proposed to play a role in a number of
      fundamental biological processes that include transcription and translation. We
      have developed a single-chain antibody that is selective for G-quadruplex DNA
      over double-stranded DNA, and here show that when it is expressed in human cells,
      it significantly affects the expression of a wide variety of genes, in a manner
      that correlates with the presence of predicted G-quadruplexes. We observe cases
      where gene expression is increased or decreased, and that there are apparent
      interactions with G-quadruplex motifs at the beginning and end of the genes, and
      on either strand. The outcomes of this genome-wide study demonstrate that G
      quadruplex recognition by the antibody has physiological consequences, and
      provides insights into some of the complexity associated with G-quadruplex-based
      regulation.

PMID- 19745056
TI  - Synthesis of DNA fragments in yeast by one-step assembly of overlapping
      oligonucleotides.
AB  - Here it is demonstrated that the yeast Saccharomyces cerevisiae can take up and
      assemble at least 38 overlapping single-stranded oligonucleotides and a linear
      double-stranded vector in one transformation event. These oligonucleotides can
      overlap by as few as 20 bp, and can be as long as 200 nucleotides in length. This
      straightforward scheme for assembling chemically-synthesized oligonucleotides
      could be a useful tool for building synthetic DNA molecules.

PMID- 19745057
TI  - RET mutation scanning update: exon 15.

PMID- 19745058
TI  - Plasma MicroRNAs as sensitive and specific biomarkers of tissue injury.
AB  - BACKGROUND: MicroRNAs (miRNAs) are endogenous, small noncoding RNAs. Because of
      their size, abundance, tissue specificity, and relative stability in plasma,
      miRNAs hold promise as unique accessible biomarkers to monitor tissue injury.
      METHODS: We investigated the use of liver-, muscle- and brain-specific miRNAs as
      circulating biomarkers of tissue injury. We used a highly sensitive quantitative
      PCR assay to measure specific miRNAs (miR-122, miR-133a, and miR-124) in plasma
      samples from rats treated with liver or muscle toxicants and from a rat surgical
      model of stroke. RESULTS: We observed increases in plasma concentrations of miR
      122, miR-133a, and miR-124 corresponding to injuries in liver, muscle, and brain,
      respectively. miR-122 and miR-133a illustrated specificity for liver and muscle
      toxicity, respectively, because they were not detectable in the plasma of animals
      with toxicity to the other organ. This result contrasted with the results for
      alanine aminotransferase (ALT) and aspartate aminotransferase, which were both
      increased with either organ toxicity. Furthermore, miR-122 exhibited a diagnostic
      sensitivity superior to that of ALT when the results were correlated to the liver
      histopathologic results. The miR-124 concentration increased in the plasma of
      rats 8 h after surgery to produce brain injury and peaked at 24 h, while the miR
      122 and miR-133a concentrations remained at baseline values. CONCLUSIONS: These
      results demonstrate that tissue-specific miRNAs may serve as diagnostically
      sensitive plasma biomarkers of tissue injury.

PMID- 19745059
TI  - Presence and characterization of cell-free seminal RNA in healthy individuals:
      implications for noninvasive disease diagnosis and gene expression studies of the
      male reproductive system.
AB  - BACKGROUND: We recently detected cell-free seminal RNA (cfsRNA) and set out to
      study its concentration, integrity, stability in healthy individuals, and
      mechanisms for its protection from ribonucleases. METHODS: We quantified cfsRNA
      by reverse-transcription quantitative real-time PCR (RT-qPCR) targeting of the 5'
      region of the ACTB (actin, beta) transcript. cfsRNA integrity was analyzed by
      microcapillary electrophoresis and by amplification of full-length ACTB and DDX4
      [DEAD (Asp-Glu-Ala-Asp) box polypeptide 4] transcripts, including measurement of
      the relative amounts of different regions of ACTB and DDX4 transcripts. Stability
      of cfsRNA was measured by time-course analysis of different regions of ACTB and
      DDX4 transcripts. To investigate whether cfsRNA was protected in complexed forms,
      we processed seminal plasma in 2 ways: filtration through pores of different
      sizes and Triton X-100 treatment before RNA recovery. RESULTS: cfsRNA
      concentrations varied from 0.87-3.64 mg/L [mean (SD), 1.75 mg/L (0.92 mg/L)].
      Most cfsRNA was present in partially degraded forms, with smaller amounts of
      middle and 3' amplicons compared with 5' amplicons. Although the 3' region of the
      DDX4 transcript was degraded completely by 90 min, the 5' regions of ACTB and
      DDX4 transcripts were stable up to 24 h. Filtration through 0.22-mum pores
      reduced ACTB and DDX4 mRNA concentrations by 72% and 61%, respectively. Nearly
      all seminal ACTB and DDX4 mRNA disappeared after Triton X-100 treatment.
      CONCLUSIONS: Although cfsRNA was partially degraded, it represented diverse
      transcript species and was abundant, fairly stable, and associated with particles
      in healthy individuals. cfsRNA may represent a potential noninvasive biomarker of
      the male reproductive system and of germline epigenetics.

PMID- 19745060
TI  - Comparison of urinary albumin quantification by immunoturbidimetry, competitive
      immunoassay, and protein-cleavage liquid chromatography-tandem mass spectrometry.
AB  - BACKGROUND: Increased urinary albumin excretion is a well-documented diagnostic
      and prognostic biomarker for renal disease. Urinary albumin is typically measured
      in clinical settings by immunoassay methods. However, neither a reference method
      nor a urine albumin calibration reference material is currently available.
      METHODS: We quantified urinary albumin in patient samples by using 3 commercially
      available reagent systems: DiaSorin SPQ and Beckman Coulter LX 20
      (immunoturbidimetric), and Siemens Immulite (competitive immunoassay). Results
      were compared to values obtained by protein-cleavage liquid chromatography-tandem
      mass spectrometry (LC-MS/MS). RESULTS: In general, results from the 3
      immunoassays agreed with results from LC-MS/MS. However, the SPQ results showed a
      negative bias across all ranges of albuminuria [(0-200 mg/L, y = 0.91x - 3.74 (CI
      0.86-0.96); > 200 mg/L, y = 0.88x - 40.30 (CI 0.76-1.00)], whereas the LX 20
      showed minimal bias in the 0-200 mg/L range [y = 0.97x - 88 (CI 0.92-1.02)] and
      the Immulite assay showed positive bias in the 0-200 mg/L range [y = 1.15x - 4.38
      (CI 1.09-1.20)]. CONCLUSIONS: These results showed a reasonable quantification of
      urinary albumin by representative polyclonal and monoclonal immunoassays compared
      to an LC-MS/MS assay. In addition, the results do not suggest the presence of
      nonimmunoreactive albumin in urine. However, differences in analytic performance
      between assays support the need for a reference calibration material and
      reference method to standardize clinical laboratory measurements of urinary
      albumin.

PMID- 19745061
TI  - A high-sensitivity, medium-density, and target amplification-free planar
      waveguide microarray system for gene expression analysis of formalin-fixed and
      paraffin-embedded tissue.
AB  - BACKGROUND: Many microarray platforms and their associated assay chemistries do
      not work properly with RNA extracted from formalin-fixed, paraffin-embedded
      (FFPE) tissue samples, a feature that severely hampers the use of microarrays in
      oncology applications, for which FFPE tissue is the routine specimen.
      Furthermore, the limited sensitivity of most microarray platforms requires time
      consuming and costly amplification reactions of the target RNA, which negatively
      affects clinical laboratory work flow. METHODS: We developed an approach for
      sensitively and reliably measuring mRNA abundances in FFPE tissue samples. This
      approach involves automated RNA extractions, direct hybridization of extracted
      RNA to immobilized capture probes, antibody-mediated labeling, and readout with
      an instrument applying the principle of planar waveguides (PWG). A 14-gene
      multiplex assay conducted with RNA isolated from 20 FFPE blocks was correlated to
      an analysis of the same with reverse-transcription quantitative real-time PCR (RT
      qPCR). RESULTS: The assay sensitivity for gene expression analysis obtained for
      the PWG microarray platform was <10 fmol/L, eliminating the need for target
      preamplification. We observed a correlation coefficient of 0.87 to state-of-the
      art RT-qPCR technology with RNA isolated from FFPE tissue, despite a compressed
      dynamic range for the PWG system (a 2.9-log dynamic range for PWG in our test
      system vs 5.0 logs for RT-qPCR). The precision of the PWG platform was comparable
      to RT-qPCR (Pearson correlation coefficient of 0.9851 for PWG vs 0.9896 for RT
      qPCR) for technical replicates. CONCLUSIONS: The presented PWG platform
      demonstrated excellent sensitivity and precision and is especially well suited
      for any application for which fast, simple, and robust multiplex assays of RNA in
      FFPE tissue are required.

PMID- 19745062
TI  - Oral fluid testing for drugs of abuse.
AB  - BACKGROUND: Oral fluid (OF) is an exciting alternative matrix for monitoring
      drugs of abuse in workplace, clinical toxicology, criminal justice, and driving
      under the influence of drugs (DUID) programs. During the last 5 years, scientific
      and technological advances in OF collection, point-of-collection testing devices,
      and screening and confirmation methods were achieved. Guidelines were proposed
      for workplace OF testing by the Substance Abuse and Mental Health Services
      Administration, DUID testing by the European Union's Driving under the Influence
      of Drugs, Alcohol and Medicines (DRUID) program, and standardization of DUID
      research. Although OF testing is now commonplace in many monitoring programs, the
      greatest current limitation is the scarcity of controlled drug administration
      studies available to guide interpretation. CONTENT: This review outlines OF
      testing advantages and limitations, and the progress in OF that has occurred
      during the last 5 years in collection, screening, confirmation, and
      interpretation of cannabinoids, opioids, amphetamines, cocaine, and
      benzodiazepines. We examine controlled drug administration studies, immunoassay
      and chromatographic methods, collection devices, point-of-collection testing
      device performance, and recent applications of OF testing. SUMMARY: Substance
      Abuse and Mental Health Services Administration approval of OF testing was
      delayed because questions about drug OF disposition were not yet resolved, and
      collection device performance and testing assays required improvement. Here, we
      document the many advances achieved in the use of OF. Additional research is
      needed to identify new biomarkers, determine drug detection windows, characterize
      OF adulteration techniques, and evaluate analyte stability. Nevertheless, there
      is no doubt that OF offers multiple advantages as an alternative matrix for drug
      monitoring and has an important role in DUID, treatment, workplace, and criminal
      justice programs.

PMID- 19745063
TI  - High levels of tumor necrosis factor-alpha contribute to accelerated loss of
      cartilage in diabetic fracture healing.
AB  - Diabetes interferes with fracture repair; therefore, we investigated mechanisms
      of impaired fracture healing in a model of multiple low-dose streptozotocin
      induced diabetes. Microarray and gene set enrichment analysis revealed an up
      regulation of gene sets related to inflammation, including tumor necrosis factor
      (TNF) signaling in the diabetic group, when cartilage is being replaced by bone
      on day 16, but not on days 12 or 22. This change coincided with elevated
      osteoclast numbers and accelerated removal of cartilage in the diabetic group (P
      < 0.05), which was reflected by smaller callus size. When diabetic mice were
      treated with the TNF-specific inhibitor, pegsunercept, the number of osteoclasts,
      cartilage loss, and number of TNF-alpha and receptor activator for nuclear factor
      kB ligand positive chondrocytes were significantly reduced (P < 0.05). The
      transcription factor forkhead box 01 (FOXO1) was tested for mediating TNF
      stimulation of osteoclastogenic and inflammatory factors in bone morphogenetic
      protein 2 pretreated ATDC5 and C3H10T1/2 chondrogenic cells. FOXO1 knockdown by
      small-interfering RNA significantly reduced TNF-alpha, receptor activator for
      nuclear factor kB ligand, macrophage colony-stimulating factor, interleukin
      1alpha, and interleukin-6 mRNA compared with scrambled small-interfering RNA. An
      association between FOXO1 and the TNF-alpha promoter was demonstrated by
      chromatin immunoprecipitation assay. Moreover, diabetes increased FOXO1 nuclear
      translocation in chondrocytes in vivo and increased FOXO1 DNA binding activity in
      diabetic fracture calluses (P < 0.05). These results suggest that diabetes
      enhanced TNF-alpha increases the expression of resorptive factors in chondrocytes
      through a process that involves activation of FOXO1 and that TNF-alpha
      dysregulation leads to enhanced osteoclast formation and accelerated loss of
      cartilage.

PMID- 19745064
TI  - Modulation of the tumor suppressor protein alpha-catenin by ischemic
      microenvironment.
AB  - Dysregulation or mislocalization of cell adhesion molecules and their regulators,
      such as E-cadherin, beta-catenin, and alpha-catenin, usually correlates with loss
      of polarity, dedifferentiation, invasive tumor growth, and metastasis. A
      subpopulation of alpha-catenin-negative cells within the DLD-1 colorectal
      carcinoma cell line causes it to display a heterogeneous morphological makeup,
      thus providing an excellent model system in which to investigate the role of
      alpha-catenin in tumorigenesis. We re-established expression of alpha-catenin
      protein in an alpha-catenin-deficient subpopulation of the DLD-1 cell line and
      used it to demonstrate that loss of alpha-catenin resulted in increased in vitro
      tumorigenic characteristics (increased soft agarose colony formation, clonogenic
      survival after suspension, and survival in suspension). When the cells were used
      to form tumor xenografts, those lacking alpha-catenin showed faster growth rates
      because of increased cellular cycling but not increased tumor microvascular
      recruitment. alpha-Catenin-expressing cells were preferentially located in well
      perfused areas of xenografts when tumors were formed from mixed alpha-catenin
      positive and -negative cells. We therefore evaluated the role of the ischemic
      tumor microenvironment on alpha-catenin expression and demonstrated that cells
      lose expression of alpha-catenin after prolonged exposure in vitro to
      hypoglycemic conditions. Our findings illustrate that the tumor microenvironment
      is a potent modulator of tumor suppressor expression, which has implications for
      localized nutrient deficiency and ischemia-induced cancer progression.

PMID- 19745065
TI  - The effect of plasma from muscle-specific tyrosine kinase myasthenia patients on
      regenerating endplates.
AB  - Muscle-specific tyrosine kinase (MuSK) is essential for clustering of
      acetylcholine receptors (AChRs) at embryogenesis and likely also important for
      maintaining synaptic structure in adult muscle. In 5 to 7% of myasthenia gravis
      (MG) cases, the patients' blood contains antibodies to MuSK. To investigate the
      effect of MuSK-MG antibody on synapse regeneration, notexin was used to induce
      damage to the flexor digitorum brevis muscle. We administered aliquots of MuSK-MG
      patients' plasma to the flexor digitorum brevis twice daily for a period up to 21
      days, and muscles were investigated ex vivo in contraction experiments. AChR
      levels were measured with (125)I-alpha-bungarotoxin, and endplates were studied
      with quantitative immunohistochemistry. In normal muscles and in 14-day
      regenerated muscles, MuSK plasma caused impairment of nerve stimulus-induced
      contraction in the presence of 0.35 and 0.5 mmol/L Ca(2+) with or without 100 to
      400 nmol/L tubocurarine. Endplate size was decreased in regenerated muscles
      relative to controls; however, we did not observe such differences in muscle not
      treated with notexin. MuSK plasma had no effect on the amount and turnover rate
      of AChRs. Our results suggest that anti-MuSK antibodies influence the activity of
      MuSK molecules without reducing their number, thereby diminishing the size of the
      endplate and affecting the functioning of AChRs.

PMID- 19745066
TI  - Chronic lymphocytic leukemia: interplay between noncoding RNAs and protein-coding
      genes.
AB  - One of the most unexpected and fascinating discoveries in oncology over the past
      few years is the interplay between abnormalities in protein-coding genes and
      noncoding RNAs (ncRNAs) that is causally involved in cancer initiation,
      progression, and dissemination. MicroRNAs (miRNAs), small regulatory ncRNAs, are
      involved in the pathogenesis of all types of human cancers, including leukemias,
      mainly via dysregulation of expression of cancer genes. Increasing evidence shows
      that miRNAs can work as tumor suppressors (inhibiting malignant potential) or
      oncogenes (activating malignant potential). Researchers first identified this new
      paradigm of molecular oncology in patients with chronic lymphocytic leukemia
      (CLL). Understanding the roles of miRNAs and other ncRNAs in leukemic cells is
      not only uncovering a new layer of gene regulation but also providing new markers
      for improved diagnosis and prognosis, as well as novel therapeutic options for
      CLL patients. Herein we focus on the roles of miRNAs and ultraconserved ncRNA
      genes in CLL, highlighting what is already known about their function, proposing
      a novel model of CLL predisposition and progression, and describing the
      challenges for the near future.

PMID- 19745067
TI  - Evaluation of pentostatin in corticosteroid-refractory chronic graft-versus-host
      disease in children: a Pediatric Blood and Marrow Transplant Consortium study.
AB  - There is no standard therapy for steroid-refractory chronic graft-versus-host
      disease (GVHD). This problem is particularly daunting in children with chronic
      GVHD, whereby the effects of the disease and its treatment may impair normal
      growth and development. Children are also particularly vulnerable to failure
      and/or toxicity of therapy; for example, joint contractures or joint damage may
      result in life-long disability. The Pediatric Blood and Marrow Transplant
      Consortium performed a phase 2 trial of pentostatin for steroid-refractory
      chronic GVHD in 51 children (median age, 9.8 years) from 24 institutions. Overall
      response was 53% (95% confidence interval, 40%-64%), with a response of 59% (95%
      confidence interval, 42%-75%) in sclerosis. Thirteen subjects (25%) had toxicity
      requiring them to stop pentostatin. The drug had a significant steroid-sparing
      effect in those that responded. A trend was also observed toward increased
      survival at 3 years in responders versus nonresponders (69% vs 50%; P = .06). The
      intravenous administration of the drug ensures compliance in a patient group in
      which oral therapy is difficult to monitor. Pentostatin has activity in
      refractory chronic GVHD in children, and future studies, including treatment of
      children newly diagnosed with high-risk chronic GVHD, are warranted. The trial
      was registered at www.Clinicaltrials.gov as #NCT00144430.

PMID- 19745068
TI  - Characterization of complement factor H-related (CFHR) proteins in plasma reveals
      novel genetic variations of CFHR1 associated with atypical hemolytic uremic
      syndrome.
AB  - The factor H-related protein family (CFHR) is a group of minor plasma proteins
      genetically and structurally related to complement factor H (fH). Notably,
      deficiency of CFHR1/CFHR3 associates with protection against age-related macular
      degeneration and with the presence of anti-fH autoantibodies in atypical
      hemolytic uremic syndrome (aHUS). We have developed a proteomics strategy to
      analyze the CFHR proteins in plasma samples from controls, patients with aHUS,
      and patients with type II membranoproliferative glomerulonephritis. Here, we
      report on the identification of persons carrying novel deficiencies of CFHR1,
      CFHR3, and CFHR1/CFHR4A, resulting from point mutations in CFHR1 and CFHR3 or
      from a rearrangement involving CFHR1 and CFHR4. Remarkably, patients with aHUS
      lacking CFHR1, but not those lacking CFHR3, present anti-fH autoantibodies,
      suggesting that generation of these antibodies is specifically related to CFHR1
      deficiency. We also report the characterization of a novel CFHR1 polymorphism,
      resulting from a gene conversion event between CFH and CFHR1, which strongly
      associates with aHUS. The risk allotype CFHR1*B, with greater sequence similarity
      to fH, may compete with fH, decreasing protection of cellular surfaces against
      complement damage. In summary, our comprehensive analyses of the CFHR proteins
      have improved our understanding of these proteins and provided further insights
      into aHUS pathogenesis.

PMID- 19745069
TI  - Aberrant splicing of the E-cadherin transcript is a novel mechanism of gene
      silencing in chronic lymphocytic leukemia cells.
AB  - Premature termination codon (PTC) mutations are due to insertion or deletion of
      nucleotides causing a frameshift and premature termination codon in RNA. These
      transcripts are degraded by the nonsense-mediated decay pathway and have a very
      short half-life. We used a microarray technique to screen for genes that up
      regulate their RNA signal upon nonsense-mediated decay pathway blockade in
      chronic lymphocytic leukemia (CLL) specimens and identified an E-cadherin
      transcript with PTC. Sequencing revealed an aberrant E-cadherin transcript
      lacking exon 11, resulting in a frameshift and PTC. The aberrant E-cadherin
      transcript was also identified in normal B cells, but occurred at a much lower
      level compared with CLL cells. In CLL specimens, E-cadherin expression was
      depressed more than 50% in 62% cases (relative to normal B cells). By real-time
      polymerase chain reaction analysis, the relative amounts of wild-type transcript
      inversely correlated with amounts of aberrant transcript (P = .018). Ectopic
      expression of E-cadherin in CLL specimens containing high amounts of aberrant
      transcript resulted in down-regulation of the wnt-beta-catenin pathway reporter,
      a pathway known to be up-regulated in CLL. Our data point to a novel mechanism of
      E-cadherin gene inactivation, with CLL cells displaying a higher proportion of
      aberrant nonfunctional transcripts and resulting up-regulation of the wnt-beta
      catenin pathway.

PMID- 19745071
TI  - TERTrific hormones promote hematopoiesis.

PMID- 19745070
TI  - VH4-34+ hairy cell leukemia, a new variant with poor prognosis despite standard
      therapy.
AB  - Hairy cell leukemia variant (HCLv) presents with high disease burden, lack of
      typical antigens like CD25, and poor response to standard treatments like
      cladribine. Occasionally, patients with classic HCL respond poorly. Clinical and
      molecular features of HCL and HCLv has not been compared. Rearrangements
      expressing immunoglobulin VH chain were sequenced, including 22 from 20 patients
      with HCLv and 63 from 62 patients with classic HCL. Most patients were seeking
      relapsed/refractory trials, representing a poor-prognosis population. VH4-34, a
      gene commonly used in autoimmune disorders, was observed in 8 (40%) HCLv and 6
      (10%) classic (P = .004) HCL patients. Compared with 71 VH4-34(-) rearrangements,
      14 VH4-34(+) rearrangements were more frequently (P < .001) unmutated, defined as
      greater than 98% homologous to germline sequence. VH4-34(+) patients had greater
      white blood cell counts at diagnosis (P = .002), lower response rate (P < .001)
      and progression-free survival (P = .007) after initial cladribine, and shorter
      overall survival from diagnosis (P < .001). Response and survival were more
      closely related to VH4-34 status than to whether or not patients had HCLv. VH4
      34(+) HCL is an important disorder that only partly overlaps with the previously
      described HCLv. Response to initial single-agent cladribine therapy is
      suboptimal; these patients should be considered for alternative approaches,
      including antibody-related therapy.

PMID- 19745072
TI  - Tolerance: pregnancy matters.

PMID- 19745073
TI  - RBC transfusion and BMT rejection.

PMID- 19745074
TI  - The osteoblastic niche following TBI.

PMID- 19745076
TI  - Degree of immune suppression and risk of HIV-related Hodgkin lymphoma: time
      points matter.

PMID- 19745077
TI  - A monoclonal gammopathy in search of clinical significance: 57 years later.

PMID- 19745079
TI  - Does HUMARA assay for assessment of clonal hematopoiesis have shortcomings?

PMID- 19745081
TI  - Therapeutic use of tea derivatives: all that glitters is not gold.

PMID- 19745082
TI  - Iron excess treatable by copper supplementation in acquired aceruloplasminemia: a
      new form of secondary human iron overload?

PMID- 19745083
TI  - Injury to the preterm brain and cerebral palsy.

PMID- 19745084
TI  - Injury to the preterm brain and cerebral palsy: clinical aspects, molecular
      mechanisms, unanswered questions, and future research directions.
AB  - Cerebral palsy will affect nearly 10% of the 60,000 very low-birth-weight infants
      born in the United States in the next year, and an even greater percentage will
      display some form of permanent neurological impairment resulting from injury to
      the preterm brain. The 2008 Neurobiology of Disease in Children Symposium, held
      in conjunction with the 37th annual meeting of the Child Neurology Society, aimed
      to define current knowledge and to develop specific aims for future clinical,
      translational, and fundamental science. A complex interplay of both destructive
      and developmental forces is responsible for injury to the preterm brain. Advances
      in imaging and histology have implicated a variety of cell types, though
      preoligodendrocyte injury remains the focus. Research into different mechanisms
      of injury is facilitating new neuroprotective and rehabilitative interventions. A
      cooperative effort is necessary to translate basic research findings into
      clinically effective therapies and better care for these children.

PMID- 19745085
TI  - Cerebellum of the premature infant: rapidly developing, vulnerable, clinically
      important.
AB  - Brain abnormality in surviving premature infants is associated with an enormous
      amount of neurodevelopmental disability, manifested principally by cognitive,
      behavioral, attentional, and socialization deficits, most commonly with only
      relatively modest motor deficits. The most recognized contributing neuropathology
      is cerebral white matter injury. The thesis of this review is that acquired
      cerebellar abnormality is a relatively less recognized but likely important cause
      of neurodevelopmental disability in small premature infants. The cerebellar
      disease may be primarily destructive (eg, hemorrhage, infarction) or primarily
      underdevelopment. The latter appears to be especially common and relates to a
      particular vulnerability of the cerebellum of the small premature infant. Central
      to this vulnerability are the extraordinarily rapid and complex developmental
      events occurring in the cerebellum. The disturbance of development can be caused
      either by direct adverse effects on the cerebellum, especially the distinctive
      transient external granular layer, or by indirect remote trans-synaptic effects.
      This review describes the fascinating details of cerebellar development, with an
      emphasis on events in the premature period, the major types of cerebellar
      abnormality acquired during the premature period, their likely mechanisms of
      occurrence, and new insights into the relation of cerebellar disease in early
      life to subsequent cognitive/behavioral/attentional/socialization deficits.

PMID- 19745086
TI  - Magnetic resonance imaging and ultrasound injury in preterm infants with
      seizures.
AB  - Although the utility of magnetic resonance imaging (MRI) as a universal screening
      tool in preterm infants has been contested, it is increasingly used to
      investigate neonatal seizures. The authors evaluated 236 infants <34 weeks'
      gestation at birth. Seizures were documented according to the clinical standard
      of care. Infants underwent MRI and head ultrasound during the neonatal period,
      and a neuroradiologist and ultrasonologist performed detailed reviews of the
      images. During the hospital course, 9 infants (3.8%) had clinical suspicion of
      seizures. Magnetic resonance imaging was abnormal in each case. Periventricular
      hemorrhagic infarct was more common in infants with seizures. Infants with
      seizures were more likely to have white matter injury, though the difference was
      not significant. Head ultrasound failed to detect the extent of brain abnormality
      in 8 (89%) of the infants. In this large cohort, infants with clinical suspicion
      of seizures had a high rate of MRI abnormalities that were not as well
      characterized by head ultrasound. Magnetic resonance imaging may be the study of
      choice for evaluating preterm infants with seizures.

PMID- 19745088
TI  - ''Intraventricular'' hemorrhage and cystic periventricular leukomalacia in
      preterm infants: how are they related?
AB  - Intraventricular hemorrhage and cystic periventricular leukomalacia are often co
      occurring characteristics of brain damage in preterm infants. Using data from
      1016 infants born before 30 completed weeks' gestational age, we sought to
      clarify the relationship between severe intraventricular hemorrhage and cystic
      periventricular leukomalacia, with special emphasis on common antecedents and
      potential confounding. After comparing risk factors for intraventricular
      hemorrhage grades 1 through 4 and cystic periventricular leukomalacia, it appears
      the risk patterns for intraventricular hemorrhage grade 3, intraventricular
      hemorrhage grade 4, and cystic periventricular leukomalacia differ. The
      association between intraventricular hemorrhage grade 3 and cystic
      periventricular leukomalacia differs appreciably from the association between
      intraventricular hemorrhage grade 4 and cystic periventricular leukomalacia,
      supporting the notion that intraventricular hemorrhage grade 3 and
      intraventricular hemorrhage grade 4 are different entities. The presence of
      intraventricular hemorrhage grade 3 and intraventricular hemorrhage grade 4
      increases the risk of cystic periventricular leukomalacia, even after adjusting
      for potential confounders. This raises the possibility that intraventricular
      hemorrhage grade 3 and intraventricular hemorrhage grade 4 cause cystic
      periventricular leukomalacia.

PMID- 19745087
TI  - The role of systemic hemodynamic disturbances in prematurity-related brain
      injury.
AB  - Premature infants who experience cerebrovascular injury frequently have acute and
      long-term neurologic complications. In this article, we explore the relationship
      between systemic hemodynamic insults and brain injury in this patient population
      and the mechanisms that might be at play.

PMID- 19745089
TI  - White matter damage after chronic subclinical inflammation in newborn mice.
AB  - Preterm infants exposed to inflammation are at increased risk of white matter
      injury and/or cerebral palsy. To investigate the effect of chronic inflammation
      on the developing white matter, we administered low-dose lipopolysaccharide once
      a day from postnatal days 3 to 11, examined white matter changes at postnatal day
      12, and monitored serum levels of insulin-like growth factor 1 and insulin-like
      factor binding protein-3. A single injection of lipopolysaccharide decreased the
      serum insulin-like growth factor 1 level but not the insulin-like factor binding
      protein-3 level. At postnatal day 12, quantification of immunohistochemical
      staining for axonal, myelin, and oligodendrocyte markers revealed impaired
      myelination in subcortical white matter. In addition, brain gray matter volume
      decreased and spleen and liver weight increased at postnatal day 12. These data
      suggest chronic subclinical inflammation hampers development of white and gray
      matter in early life, which may be associated with insulin-like growth factor 1
      deficiency.

PMID- 19745090
TI  - Intrauterine endotoxin administration leads to white matter diffusivity changes
      in newborn rabbits.
AB  - Maternal intrauterine inflammation has been implicated in the development of
      periventricular leukomalacia and white matter injury in the neonate. We
      hypothesized that intrauterine endotoxin administration would lead to
      microstructural changes in the neonatal rabbit white matter in vivo that could be
      detected at birth using diffusion tensor magnetic resonance imaging (MRI). Term
      newborn rabbit kits (gestational age 31 days) born to dams exposed to saline or
      endotoxin in utero on gestational day 28 underwent diffusion tensor imaging, and
      brain sections were stained for microglia. Comparison between normal and
      endotoxin groups showed significant decreases in both fractional anisotropy and
      eigenvalue (e(1)) in all periventricular white matter regions that showed an
      increase in the number of activated microglial cells, indicating that after
      maternal inflammation, microglial infiltration may predominantly explain this
      change in diffusivity in the immediate neonatal period. Diffusion tensor imaging
      may be a clinically useful tool for detecting neuroinflammation induced by
      maternal infection in neonatal white matter.

PMID- 19745092
TI  - White matter damage impairs adaptive recovery more than cortical damage in an in
      silico model of activity-dependent plasticity.
AB  - Little is understood of how damaged white matter interacts with developmental
      plasticity. The authors propose that computational neuroscience methods are
      underused in this problem. In this article, they present a nondeterministic, in
      silico model of activity-dependent plasticity. Using this model, they compared
      the impact of neuronal cell loss or axonal dysfunction on the ability of the
      system to generate, maintain, and recover synapses. The results suggest the
      axonal dysfunction seen in white matter injury is a greater burden to adaptive
      plasticity and recovery than is the neuronal loss of cortical injury. Better
      understanding of the interaction between features of preterm brain injury and
      developmental plasticity is an essential component for improving recovery.

PMID- 19745091
TI  - Positron emission tomography imaging of neuroinflammation.
AB  - Injury to the central nervous system is characterized by localization of
      activated microglia at the site of injury. The peripheral benzodiazepine receptor
      expressed on the outer mitochondrial membrane of the activated microglia is a
      sensitive biomarker for the detection of this neuroinflammatory response to an
      insult. PK11195, an isoquinoline ligand that specifically binds peripheral
      benzodiazepine receptor, can be tagged with a positron emitter and used as a
      tracer for molecular imaging of this receptor in vivo by positron emission
      tomography (PET). [(11)C](R)PK11195 has been used in the imaging of various
      neuroinflammatory disorders, such as Alzheimer disease and multiple sclerosis. On
      the basis of our small-animal PET imaging studies using a neonatal rabbit model
      of maternal inflammation-induced cerebral palsy, we propose that PET imaging
      using [(11)C](R)PK11195 may be a valuable tool for detecting neuroinflammation in
      the brain of newborns born to mothers with chorioamnionitis.

PMID- 19745093
TI  - Neuroprotective interventions: is it too late?
AB  - In most cases of neonatal hypoxic-ischemic encephalopathy, the exact timing of
      the hypoxic-ischemic event is unknown, and we have few reliable biomarkers to
      precisely identify the phase of injury or recovery in an individual patient.
      However, it is becoming increasingly clear that for neuroprotection in neonates
      to succeed, an understanding of the phase of injury is important to ascertain. In
      addition, in utero antecedents of chronic hypoxia, hypoxic preconditioning,
      intrauterine infection, and fetal gender may change the expected time course of
      injury. Neuroprotective interventions, such as hypothermia and N-acetylcysteine,
      currently have efficacy in human and animal studies only if instituted early in
      the inflammatory cascade. Although these cascades are currently being
      investigated, molecular mechanisms of recovery have received little attention and
      may ultimately reveal a window for therapeutic intervention that is much longer
      than current paradigms.

PMID- 19745095
TI  - Parent perception of healthy infant and toddler growth.
AB  - We hypothesized that parents of infants prefer growth at higher percentiles and
      are averse to growth at lower percentiles. Of 279 participating parents, only 10%
      desired their child's weight to be in the lowest quartile. For children weighing
      in the lowest quartile, 57% of parents thought their child's weight was "too
      low." In contrast, 66% of parents whose child's weight was in the top quartile
      preferred their child weigh that much. When viewing hypothetical infant growth
      trajectories, 47% ranked a growth chart demonstrating growth along the 10th
      percentile for weight as "least healthy" of 6 growth patterns, and 29% chose
      charts showing an infant at the 90th percentile for weight at age 1 as
      "healthiest." In conclusion, parents are averse to growth at the bottom of the
      weight growth chart but are much less likely to feel negatively about growth at
      higher percentiles. This is troubling given the childhood obesity epidemic.

PMID- 19745096
TI  - Type 2 diabetes in the pediatric population: Are we meeting ADA clinical
      guidelines in Ohio?
AB  - Several studies have demonstrated the importance of achieving the American
      Diabetes Association (ADA) clinical guidelines in adults. However, research is
      limited on adherence to these guidelines in the pediatric population. This
      retrospective chart review examined 56 charts from 6 physician offices and 1
      multispecialty health care system in Ohio. Variables of interest included
      recommendations from the 2007 ADA Standards of Medical Care in Diabetes. HgA1c
      was measured every 3 months in 44.6% of patients, while 55% achieved A1c goal.
      Blood pressure was monitored in all patients, with 57% meeting goal. Lipids and
      urine microalbumin were tested annually in 51.7% and 26.7% of patients,
      respectively. Dilated eye and foot exams were performed on 53.5% and 37.5% of
      patients, respectively. Adherence to ADA clinical guidelines for pediatric
      patients with type 2 diabetes is suboptimal. The authors recommend that specific
      evidence-based guidelines be evaluated for children with type 2 diabetes.

PMID- 19745097
TI  - Provider compliance with the Food and Drug Administration recommendation to avoid
      the use of over-the-counter (nonprescription) cough and cold medications in
      children younger than 2 years.

PMID- 19745098
TI  - Hematemesis and pyloric stenosis.

PMID- 19745099
TI  - Pediatrician's role in children's oral health: an Indiana survey.
AB  - OBJECTIVES: To evaluate Indiana pediatricians' current practices related to oral
      health, knowledge of oral health prevention, and opinions on anticipatory
      guidance integration into their practices. BACKGROUND: The American Academy of
      Pediatrics (AAP) May 2003 policy statement on oral health risk assessment timing
      and establishment of a dental home has provided pediatricians with guidelines to
      assess patients' oral health and caries risk status. METHODS: A survey of 31
      questions was distributed via mail to all active Indiana pediatricians (300)
      registered in the Indiana State Medical Association to evaluate current practices
      relating to oral health prevention and guidance. RESULTS: Of the 300 distributed
      surveys, 138 were returned (46%). The authors found that 15% of pediatricians
      recognize the AAP-recommended age for a dental home as 12 months and practice
      this recommendation. Among the respondents, 7% believe application of fluoride
      should be part of a well-child visit. The majority (89%) of respondents reported
      interest in obtaining further knowledge on oral health.

PMID- 19745100
TI  - Obesity with necrotizing gallstone pancreatitis.

PMID- 19745103
TI  - Klotho reduces apoptosis in experimental ischaemic acute kidney injury via HSP
      70.
AB  - BACKGROUND: High Klotho expression has been detected in the kidney, and since the
      results of a recent study suggested that Klotho induction mitigates ischaemic
      damage in the kidney, in the present study we explored the mechanism by which
      Klotho expression reduces renal ischaemia-reperfusion injury (IRI). METHODS: Male
      mice were subjected to bilateral renal ischaemia for 30 min and reperfusion for
      24 h, or to a sham operation. Both the IRI group and the sham group were
      intravenously injected with an adenovirus harbouring the mouse Klotho gene (ad
      kl) before renal IRI. In addition, mIMCD3 cells induced to overexpress Klotho by
      transferring the Klotho gene with ad-kl were analysed by DNA microarray and real
      time PCR. Renal expression of Klotho and several genes selected by DNA microarray
      were assessed by real-time PCR or Western blotting, and TUNEL staining was
      performed to assess apoptosis. RESULTS: Prior administration of ad-kl to the mice
      resulted in robust induction of Klotho mRNA in the kidney and liver. Ad-kl
      transfer improved the plasma creatinine values and mitigated the histological
      damage and apoptosis induced by IRI. Expression of several genes was altered in
      mIMCD3 cells as a result of the change in Klotho expression, and expression of
      heat shock protein 70 (HSP70), in particular, was up-regulated in ad-kl mouse
      kidneys and HK2 cells. CONCLUSION: The results suggest that Klotho is involved in
      the pathophysiology of IRI. Klotho mitigates apoptosis in experimental ischaemic
      acute kidney injury via expression of HSP70.

PMID- 19745104
TI  - Effect of treatment spacing and frequency on three measures of equivalent
      clearance, including standard Kt/V.
AB  - BACKGROUND: We examined the sensitivity of three different equivalent clearances
      to the spacing of haemodialysis treatments as well as to frequency. One would
      expect that a well-spaced schedule would be beneficial, and an optimal clearance
      measure should reflect this. METHODS: Using a variable volume two-pool urea
      kinetic model, we derived clearances based on G [urea nitrogen (UN) generation
      rate] divided by time-averaged UN (G/TAC), mean predialysis UN (G/meanpre or
      'standard' Kt/V) or peak UN (G/peak) when identical dialysis treatments were
      given on a poorly spaced (Monday-Tuesday-Wednesday) versus a well-spaced (Monday
      Wednesday-Friday) schedule. We also calculated the 'gain' in each clearance when
      well-spaced treatments were given six versus three times a week. Modelling
      parameters were diffusive dialyser clearance = 283 ml/min, session length = 210
      min (105 min for 6/week), G = 7 mg/min, V = 35 l and weight gain = 10 l/week.
      RESULTS: The 'standard' Kt/V (G/meanpre) was the same with the poorly spaced
      (Monday-Tuesday-Wednesday) and well-spaced (Monday-Wednesday-Friday) schedules.
      In contrast, the G/TAC- and G/peak-based clearances were higher with the well
      spaced schedule (+20% and +37%, respectively). When total treatment time was held
      constant at 630 min/week, the gain of moving from three to six treatments per
      week was lower with G/TAC (+9%) than with G/meanpre (+29%) or with G/peak (+18%).
      When 6/week treatment time was doubled to 1260 min/week, the gains with G/TAC and
      G/pre (relative to 3/week with 630 min/week dialysis) were similar (about +94% to
      97%), but were lower with G/peak (+55%). CONCLUSIONS: All three equivalent
      clearances increased on moving from three to six sessions per week, with standard
      Kt/V having the greatest increase. Standard Kt/V is not at all sensitive to
      spacing. Alternative clearances based on the TAC or peak concentration have the
      advantage of taking both spacing and frequency into account.

PMID- 19745105
TI  - Adrenergic beta-1 receptor genetic variation predicts longitudinal rate of GFR
      decline in hypertensive nephrosclerosis.
AB  - BACKGROUND: End-stage renal disease (ESRD) due to hypertension is common and
      displays familial aggregation in African Americans, suggesting genetic risk
      factors, including adrenergic activity alterations which are noted in both
      hypertension and ESRD. METHODS: We analysed 554 hypertensive nephrosclerosis
      participants (without clinically significant proteinuria) from the longitudinal
      National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) African
      American Study of Kidney Disease and Hypertension (AASK) cohort to determine
      whether decline in glomerular filtration rate (GFR) over approximately 3.8 years
      was predicted by common genetic variation within the adrenergic beta-1 (ADRB1)
      receptor at non-synonymous positions Ser49Gly and Arg389Gly. RESULTS: The
      polymorphism at Ser49Gly (though not Arg389Gly, in only partial linkage
      disequilibrium at r(2) = 0.18) predicted the chronic rate of GFR decline, with
      minimal decline in Gly(49)/Gly(49) (minor allele) homozygotes compared to Ser(49)
      carriers; concordant results were observed for haplotypes and diploid haplotype
      pairs at the locus. An independent replication study in 1244 subjects from the
      San Diego Veterans Affairs Hypertension Cohort confirmed that Gly(49)/Gly(49)
      homozygotes displayed the least rapid decline of eGFR over approximately 3.6
      years. CONCLUSION: We conclude that GFR decline rate in hypertensive renal
      disease is controlled in part by genetic variation within the adrenergic pathway,
      particularly at ADRB1. The results suggest novel strategies to approach the role
      of the adrenergic system in the risk and treatment of progressive renal disease.

PMID- 19745106
TI  - Analysis of TSHZ2 and TSHZ3 genes in congenital pelvi-ureteric junction
      obstruction.
AB  - BACKGROUND: Congenital pelvi-ureteric junction obstruction (PUJO) affects 0.3% of
      human births. It may result from aberrant smooth muscle development in the renal
      pelvis, resulting in hydronephrosis. Mice that are null mutant for the Teashirt3
      (Tshz3) gene exhibit congenital PUJO with defective smooth muscle differentiation
      and absent peristalsis in the proximal ureter. METHODS: Given the phenotype of
      Tshz3 mutant mice, we considered that Teashirt genes, which code for a family of
      transcription factors, might represent candidate genes for human PUJO. To
      evaluate this possibility, we used in situ hydridization to analyse the three
      mammalian Tshz genes in mouse embryonic ureters and determined whether TSHZ3 was
      expressed in the human embryonic ureter. TSHZ2 and TSHZ3 were sequenced in index
      cases with non-syndromic PUJO. RESULTS: Tshz2 and Tshz3 genes were detected in
      mouse ureters and TSHZ3 was expressed in the human embryonic renal pelvis. Direct
      sequencing of TSHZ2 and TSHZ3 did not identify any mutations in an initial cohort
      of 48 PUJO index cases, excluding these genes as a major cause of this condition.
      A polymorphic missense change (E469G) in TSHZ3 was identified at a residue highly
      conserved throughout evolution in all Teashirt proteins, although subsequently no
      significant difference between the E469G allele frequency in Albanian and
      Macedonian PUJO index cases (3.2%) versus 633 control individuals (1.7%) was
      found (P = 0.18). CONCLUSIONS: Mutations in TSHZ2 and TSHZ3 are not a major cause
      of PUJO, at least in Albanian and Macedonian populations. Expression of these
      genes in the human fetal ureter emphasizes the importance of analysing these
      genes in other groups of patients with renal tract malformations.

PMID- 19745107
TI  - Importance of peritoneal dialysis catheter insertion by nephrologists: practice
      makes perfect.

PMID- 19745108
TI  - Effect of Intra-articular 4-(S)-amino-5-(4-{4-[2,4-dichloro-3-(2,4-dimethyl-8
      quinolyloxymethyl)phenylsulfonamido]-tetrahydro-2H-4-pyranylcarbonyl} piperazino)
      5-oxopentyl](trimethyl)ammonium chloride hydrochloride (MEN16132), a kinin B2
      receptor antagonist, on nociceptive response in monosodium iodoacetate-induced
      experimental osteoarthritis in rats.
AB  - The present study was designed to investigate the role of bradykinin (BK) in the
      knee joint osteoarthritis induced by intra-articular (i.ar.) administration of
      monosodium iodoacetate (MIA) in the rat, and to determine the efficacy of the
      kinin B(2) receptor antagonists, 4-(S)-amino-5-(4-{4-[2,4-dichloro-3-(2,4
      dimethyl-8-quinolyloxymethyl)phenylsulfonamido]-tetrahydro-2H-4-pyranylcarbonyl}
      piperazino)-5-oxopentyl](trimethyl)ammonium chloride hydrochloride (MEN16132) and
      icatibant, in reducing pain. Rats received MIA (1 mg/25 microl i.ar.) in the
      right knee. MEN16132, icatibant (1, 3, and 10 microg/25 microl i.ar.), or saline
      were administered 7 days after MIA treatment, and their antinociceptive effect
      was observed for 2 weeks. MEN16132 induced a marked and sustained reduction of
      incapacitation produced by MIA, approximately 56% inhibition of pain at 3
      microg/knee. MEN16132 analgesia was more potent and longer lasting, up to 10
      days, than icatibant. MEN16132 (3 microg/knee), at different time points from MIA
      treatment in separate groups of animals, produced comparable maximal
      antinociceptive effects, whereas the pain response induced by MIA was unaffected
      if MEN16132 (10 microg/knee) was administered in the contralateral knee.
      Indomethacin at high doses (100-625 microg/knee) inhibited by approximately 40%
      but with a short duration the MIA-induced pain. MIA treatment produced a
      significant increase of BK and prostaglandin E(2) (PGE(2)) metabolite levels in
      synovial fluid up to 21 days, and PGE(2) metabolite levels were reduced almost to
      basal values by MEN16132. In conclusion the potent and long-lasting analgesic
      effect of MEN16132 in MIA-induced osteoarthritis indicates an important role for
      BK in osteoarthritic pain, and suggests that MEN16132 can be a candidate for the
      treatment of this chronic disease.

PMID- 19745109
TI  - Selective enhancement of nutrient-induced insulin secretion by ATP-sensitive K+
      channel-blocking imidazolines.
AB  - The contribution of ATP-sensitive K(+) channel (K(ATP) channel)-dependent and 
      independent signaling to the insulinotropic characteristics of imidazolines was
      explored using perifused mouse islets and beta-cells. Up to a concentration of
      100 muM efaroxan had no insulinotropic effect in the presence of a basal glucose
      concentration, but enhanced the effect of a stimulatory concentration of glucose
      or nonglucidic nutrients (ketoisocaproate plus glutamine). The secretion by a non
      nutrient (40 mM KCl) was not enhanced. At 500 microM, efaroxan stimulated insulin
      secretion when glucose was basal. Likewise, at 0.1 to 10 microM RX871024 [2
      (imidazolin-2-yl)-1-phenylindole] showed a purely enhancing effect, but at 100
      microM it elicited a strong KCl-like secretory response in the presence of basal
      glucose. At 0.1 and 1 microM RX871024 did not significantly depolarize the beta
      cell membrane. However, at a purely enhancing drug concentration (10 microM
      RX871024 or 100 microM efaroxan) K(ATP) channel activity was strongly reduced,
      the membrane was depolarized, and the cytosolic Ca(2+) concentration was elevated
      in the presence of basal glucose. Insulin secretion by sulfonylurea receptor
      (SUR)1 knockout (KO) islets, which have no functional K(ATP) channels, was not
      increased by efaroxan (100 or 500 microM) or by 10 microM RX871024 but was
      increased by 100 microM RX871024. The imidazolines phentolamine and alinidine
      (100 microM) were also ineffective on SUR1 KO islets. It is concluded that a
      significant K(ATP) channel block is compatible with a purely enhancing effect of
      the imidazolines on nutrient-induced insulin secretion. Only RX871024 has an
      additional, nondepolarizing effect, which at a high drug concentration is able to
      elicit a K(ATP) channel-independent secretion.

PMID- 19745110
TI  - Bone marrow-derived CX3CR1 progenitors contribute to neointimal smooth muscle
      cells via fractalkine CX3CR1 interaction.
AB  - Smooth muscle cells play a major role in numerous vascular diseases that
      contribute to remodeling, repair after injury, and arteriogenesis, and the source
      of these cells is thought to lie within the vessel wall and the circulating
      blood. Currently, the precise origin and mechanism of differentiation of
      extravascular smooth muscle progenitor cells (SPCs) is unclear. We show here that
      the CX(3)CR1 mononuclear cell population of murine bone marrow provides a source
      of SPCs that contributes to smooth muscle cells within the neointimal plaque
      after vascular injury. Moreover, CX(3)CR1-fractalkine (FKN) interaction in vivo
      is essential for smooth muscle cell differentiation of bone marrow-derived
      progenitor cells at the vessel wall level. Functional competence of bone marrow
      derived CX(3)CR1 positive cells to interact with FKN is also crucial in part for
      neointima formation following vascular injury. Finally, in a pure preparation of
      bone marrow-derived CX(3)CR1 positive cells, we show that in vitro smooth muscle
      cell differentiation increases markedly in the presence of FKN. Our data
      highlight a novel functional relationship between the myeloid and vascular
      systems and in the context of vascular injury and repair underscores a key
      chemokine-receptor pathway that may regulate cell fate when smooth muscle cell
      differentiation is required.

PMID- 19745111
TI  - Complex selection on 5' splice sites in intron-rich organisms.
AB  - In contrast to the typically streamlined genomes of prokaryotes, many eukaryotic
      genomes are riddled with long intergenic regions, spliceosomal introns, and
      repetitive elements. What explains the persistence of these and other seemingly
      suboptimal structures? There are three general hypotheses: (1) the structures in
      question are not actually suboptimal but optimal, being favored by selection, for
      unknown reasons; (2) the structures are not suboptimal, but of (essentially)
      equal fitness to "optimal" ones; or (3) the structures are truly suboptimal, but
      selection is too weak to systematically eliminate them. The 5' splice sites of
      introns offer a rare opportunity to directly test these hypotheses. Intron-poor
      species show a clear consensus splice site; most introns begin with the same six
      nucleotide sequence (typically GTAAGT or GTATGT), indicating efficient selection
      for this consensus sequence. In contrast, intron-rich species have much less
      pronounced boundary consensus sequences, and only small minorities of introns in
      intron-rich species share the same boundary sequence. We studied rates of
      evolutionary change of 5' splice sites in three groups of closely related intron
      rich species--three primates, five Drosophila species, and four Cryptococcus
      fungi. Surprisingly, the results indicate that changes from consensus-to-variant
      nucleotides are generally disfavored by selection, but that changes from variant
      to consensus are neither favored nor disfavored. This evolutionary pattern is
      consistent with selective differences across introns, for instance, due to
      compensatory changes at other sites within the gene, which compensate for the
      otherwise suboptimal consensus-to-variant changes in splice boundaries.

PMID- 19745112
TI  - Comparison of diverse developmental transcriptomes reveals that coexpression of
      gene neighbors is not evolutionarily conserved.
AB  - Genomic analyses have shown that adjacent genes are often coexpressed. However,
      it remains unclear whether the observed coexpression is a result of functional
      organization or a consequence of adjacent active chromatin or transcriptional
      read-through, which may be free of selective biases. Here, we compare temporal
      expression profiles of one-to-one orthologs in conserved or divergent genomic
      positions in two genetically distant nematode species-Caenorhabditis elegans and
      C. briggsae-that share a near-identical developmental program. We find, for all
      major patterns of temporal expression, a substantive amount of gene expression
      divergence. However, this divergence is not random: Genes that function in
      essential developmental processes show less divergence than genes whose functions
      are not required for viability. Coexpression of gene neighbors in either species
      is highly divergent in the other, in particular when the neighborhood is not
      conserved. Interestingly, essential genes appear to maintain their expression
      profiles despite changes in neighborhoods suggesting exposure to stronger
      selection. Our results suggest that a significant fraction of the coexpression
      observed among gene neighbors may be accounted for by neutral processes, and
      further that these may be distinguished by comparative gene expression analyses.

PMID- 19745113
TI  - Comparative genomics of the fungal pathogens Candida dubliniensis and Candida
      albicans.
AB  - Candida dubliniensis is the closest known relative of Candida albicans, the most
      pathogenic yeast species in humans. However, despite both species sharing many
      phenotypic characteristics, including the ability to form true hyphae, C.
      dubliniensis is a significantly less virulent and less versatile pathogen.
      Therefore, to identify C. albicans-specific genes that may be responsible for an
      increased capacity to cause disease, we have sequenced the C. dubliniensis genome
      and compared it with the known C. albicans genome sequence. Although the two
      genome sequences are highly similar and synteny is conserved throughout, 168
      species-specific genes are identified, including some encoding known hyphal
      specific virulence factors, such as the aspartyl proteinases Sap4 and Sap5 and
      the proposed invasin Als3. Among the 115 pseudogenes confirmed in C. dubliniensis
      are orthologs of several filamentous growth regulator (FGR) genes that also have
      suspected roles in pathogenesis. However, the principal differences in genomic
      repertoire concern expansion of the TLO gene family of putative transcription
      factors and the IFA family of putative transmembrane proteins in C. albicans,
      which represent novel candidate virulence-associated factors. The results suggest
      that the recent evolutionary histories of C. albicans and C. dubliniensis are
      quite different. While gene families instrumental in pathogenesis have been
      elaborated in C. albicans, C. dubliniensis has lost genomic capacity and key
      pathogenic functions. This could explain why C. albicans is a more potent
      pathogen in humans than C. dubliniensis.

PMID- 19745114
TI  - The transmissibility and control of pandemic influenza A (H1N1) virus.
AB  - Pandemic influenza A (H1N1) 2009 (pandemic H1N1) is spreading throughout the
      planet. It has become the dominant strain in the Southern Hemisphere, where the
      influenza season has now ended. Here, on the basis of reported case clusters in
      the United States, we estimated the household secondary attack rate for pandemic
      H1N1 to be 27.3% [95% confidence interval (CI) from 12.2% to 50.5%]. From a
      school outbreak, we estimated that a typical schoolchild infects 2.4 (95% CI from
      1.8 to 3.2) other children within the school. We estimated the basic reproductive
      number, R0, to range from 1.3 to 1.7 and the generation interval to range from
      2.6 to 3.2 days. We used a simulation model to evaluate the effectiveness of
      vaccination strategies in the United States for fall 2009. If a vaccine were
      available soon enough, vaccination of children, followed by adults, reaching 70%
      overall coverage, in addition to high-risk and essential workforce groups, could
      mitigate a severe epidemic.

PMID- 19745115
TI  - Using neural measures of economic value to solve the public goods free-rider
      problem.
AB  - Every social group needs to decide when to provide public goods and how to
      allocate the costs among its members. Ideally, this decision would maximize the
      group's net benefits while also ensuring that every individual's benefit is
      greater than the cost he or she has to pay. Unfortunately, the economic theory of
      mechanism design has shown that this ideal solution is not feasible when the
      group leadership does not know the values of the individual group members for the
      public good. We show that this impossibility result can be overcome in laboratory
      settings by combining technologies for obtaining neural measures of value
      (functional magnetic resonance imaging-based pattern classification) with
      carefully designed institutions that allocate costs based on both reported and
      neurally measured values.

PMID- 19745116
TI  - RNAi in budding yeast.
AB  - RNA interference (RNAi), a gene-silencing pathway triggered by double-stranded
      RNA, is conserved in diverse eukaryotic species but has been lost in the model
      budding yeast Saccharomyces cerevisiae. Here, we show that RNAi is present in
      other budding yeast species, including Saccharomyces castellii and Candida
      albicans. These species use noncanonical Dicer proteins to generate small
      interfering RNAs, which mostly correspond to transposable elements and Y'
      subtelomeric repeats. In S. castellii, RNAi mutants are viable but have excess Y'
      messenger RNA levels. In S. cerevisiae, introducing Dicer and Argonaute of S.
      castellii restores RNAi, and the reconstituted pathway silences endogenous
      retrotransposons. These results identify a previously unknown class of Dicer
      proteins, bring the tool of RNAi to the study of budding yeasts, and bring the
      tools of budding yeast to the study of RNAi.

PMID- 19745117
TI  - Repetitive readout of a single electronic spin via quantum logic with nuclear
      spin ancillae.
AB  - Robust measurement of single quantum bits plays a key role in the realization of
      quantum computation and communication as well as in quantum metrology and
      sensing. We have implemented a method for the improved readout of single
      electronic spin qubits in solid-state systems. The method makes use of quantum
      logic operations on a system consisting of a single electronic spin and several
      proximal nuclear spin ancillae in order to repetitively readout the state of the
      electronic spin. Using coherent manipulation of a single nitrogen vacancy center
      in room-temperature diamond, full quantum control of an electronic-nuclear system
      consisting of up to three spins was achieved. We took advantage of a single
      nuclear-spin memory in order to obtain a 10-fold enhancement in the signal
      amplitude of the electronic spin readout. We also present a two-level,
      concatenated procedure to improve the readout by use of a pair of nuclear spin
      ancillae, an important step toward the realization of robust quantum information
      processors using electronic- and nuclear-spin qubits. Our technique can be used
      to improve the sensitivity and speed of spin-based nanoscale diamond
      magnetometers.

PMID- 19745118
TI  - Reconstruction of molecular orbital densities from photoemission data.
AB  - Photoemission spectroscopy is commonly applied to study the band structure of
      solids by measuring the kinetic energy versus angular distribution of the
      photoemitted electrons. Here, we apply this experimental technique to
      characterize discrete orbitals of large pi-conjugated molecules. By measuring the
      photoemission intensity from a constant initial-state energy over a hemispherical
      region, we generate reciprocal space maps of the emitting orbital density. We
      demonstrate that the real-space electron distribution of molecular orbitals in
      both a crystalline pentacene film and a chemisorbed p-sexiphenyl monolayer can be
      obtained from a simple Fourier transform of the measurement data. The results are
      in good agreement with density functional calculations.

PMID- 19745119
TI  - Redefining cancer research.

PMID- 19745120
TI  - Biomedical research. VA pulls the plug on disputed study of Gulf War illness.

PMID- 19745121
TI  - Newsmaker interview. Firefighters 'worked like demons' to save observatory.
      Interview by Yudhijit Bhattacharjee.

PMID- 19745123
TI  - Physics. Tests show moon not quite as strange as some physicists had hoped.

PMID- 19745124
TI  - Public health. A race against time to vaccinate against novel H1N1 virus.

PMID- 19745126
TI  - Archaeology. Clothes make the (hu) man.

PMID- 19745127
TI  - Evolutionary biology. How beach life favors blond mice.

PMID- 19745129
TI  - Environmental management. Science lags on saving the Arctic from oil spills.

PMID- 19745128
TI  - Evolutionary biology. Melding mammals and molecules to track evolution.

PMID- 19745130
TI  - Materials science. As China's rare earth R&D becomes ever more rarefied, others
      tremble.

PMID- 19745131
TI  - Introductory biology: top-down teaching.

PMID- 19745132
TI  - Introductory biology: let's train lecturers.

PMID- 19745133
TI  - User feedback shapes Internet progress.

PMID- 19745134
TI  - Purposeful learning with drug repurposing.

PMID- 19745135
TI  - United States acting to conserve tuna stocks.

PMID- 19745136
TI  - Taking educational research to school.

PMID- 19745137
TI  - Environment. Looming global-scale failures and missing institutions.

PMID- 19745138
TI  - Astronomy. Cosmology at a crossroads.

PMID- 19745139
TI  - Physics. The thermodynamics of quantum critical points.

PMID- 19745140
TI  - Neuroscience. Low-cost travel in neurons.

PMID- 19745141
TI  - Genetics. MITEs--the ultimate parasites.

PMID- 19745142
TI  - Neuroscience. Went fishing, caught a snake.

PMID- 19745143
TI  - Ecological dynamics across the Arctic associated with recent climate change.
AB  - At the close of the Fourth International Polar Year, we take stock of the
      ecological consequences of recent climate change in the Arctic, focusing on
      effects at population, community, and ecosystem scales. Despite the buffering
      effect of landscape heterogeneity, Arctic ecosystems and the trophic
      relationships that structure them have been severely perturbed. These rapid
      changes may be a bellwether of changes to come at lower latitudes and have the
      potential to affect ecosystem services related to natural resources, food
      production, climate regulation, and cultural integrity. We highlight areas of
      ecological research that deserve priority as the Arctic continues to warm.

PMID- 19745144
TI  - 30,000-year-old wild flax fibers.
AB  - A unique finding of wild flax fibers from a series of Upper Paleolithic layers at
      Dzudzuana Cave, located in the foothills of the Caucasus, Georgia, indicates that
      prehistoric hunter-gatherers were making cords for hafting stone tools, weaving
      baskets, or sewing garments. Radiocarbon dates demonstrate that the cave was
      inhabited intermittently during several periods dated to 32 to 26 thousand years
      before the present (kyr B.P.), 23 to 19 kyr B.P., and 13 to 11 kyr B.P. Spun,
      dyed, and knotted flax fibers are common. Apparently, climatic fluctuations
      recorded in the cave's deposits did not affect the growth of the plants because a
      certain level of humidity was sustained.

PMID- 19745145
TI  - Laser tunnel ionization from multiple orbitals in HCl.
AB  - Tunneling, one of the most striking manifestations of quantum mechanics,
      influences the electronic structure of many molecules and solids and is
      responsible for radioactive decay. Much of the interaction of intense light
      pulses with matter commences with electrons tunneling from atoms or molecules to
      the continuum. Until recently, this starting point was assumed to be the highest
      occupied orbital of a given system. We have now observed tunneling from a lower
      lying state in hydrogen chloride (HCl). Analyzing two independent experimental
      observables allowed us to isolate (via fragment ions), identify (via molecular
      frame photoelectron angular distributions), and, with the help of ab initio
      simulations, quantify the contribution of lower-lying orbitals to the total and
      angle-dependent tunneling current of the molecule. Our results bolster the
      emerging tenet that the coherent interaction between different orbitals--which
      can amplify the impact of lower orbitals--must be considered in tunneling
      processes.

PMID- 19745146
TI  - Extremely efficient multiple electron-hole pair generation in carbon nanotube
      photodiodes.
AB  - We observed highly efficient generation of electron-hole pairs due to impact
      excitation in single-walled carbon nanotube p-n junction photodiodes. Optical
      excitation into the second electronic subband E22 leads to striking photocurrent
      steps in the device I-V(SD) characteristics that occur at voltage intervals of
      the band-gap energy E(GAP)/e. Spatially and spectrally resolved photocurrent
      combined with temperature-dependent studies suggest that these steps result from
      efficient generation of multiple electron-hole pairs from a single hot E22
      carrier. This process is both of fundamental interest and relevant for
      applications in future ultra-efficient photovoltaic devices.

PMID- 19745147
TI  - Underplating in the Himalaya-Tibet collision zone revealed by the Hi-CLIMB
      experiment.
AB  - We studied the formation of the Himalayan mountain range and the Tibetan Plateau
      by investigating their lithospheric structure. Using an 800-kilometer-long,
      densely spaced seismic array, we have constructed an image of the crust and upper
      mantle beneath the Himalayas and the southern Tibetan Plateau. The image reveals
      in a continuous fashion the Main Himalayan thrust fault as it extends from a
      shallow depth under Nepal to the mid-crust under southern Tibet. Indian crust can
      be traced to 31 degrees N. The crust/mantle interface beneath Tibet is
      anisotropic, indicating shearing during its formation. The dipping mantle fabric
      suggests that the Indian mantle is subducting in a diffuse fashion along several
      evolving subparallel structures.

PMID- 19745148
TI  - Dynamic processes governing lower-tropospheric HDO/H2O ratios as observed from
      space and ground.
AB  - The hydrological cycle and its response to environmental variability such as
      temperature changes is of prime importance for climate reconstruction and
      prediction. We retrieved deuterated water/water (HDO/H2O) abundances using
      spaceborne absorption spectroscopy, providing an almost global perspective on the
      near-surface distribution of water vapor isotopologs. We observed an unexpectedly
      high HDO/H2O seasonality in the inner Sahel region, pointing to a strong isotopic
      depletion in the subsiding branch of the Hadley circulation and its
      misrepresentation in general circulation models. An extension of the analysis at
      high latitudes using ground-based observations of deltaD and a model study shows
      that dynamic processes can entirely compensate for temperature effects on the
      isotopic composition of precipitation.

PMID- 19745149
TI  - Potential for wind-generated electricity in China.
AB  - Wind offers an important alternative to coal as a source of energy for generation
      of electricity in China with the potential for substantial savings in carbon
      dioxide emissions. Wind fields derived from assimilated meteorological data are
      used to assess the potential for wind-generated electricity in China subject to
      the existing government-approved bidding process for new wind farms. Assuming a
      guaranteed price of 0.516 RMB (7.6 U.S. cents) per kilowatt-hour for delivery of
      electricity to the grid over an agreed initial average period of 10 years, it is
      concluded that wind could accommodate all of the demand for electricity projected
      for 2030, about twice current consumption. Electricity available at a concession
      price as low as 0.4 RMB per kilowatt-hour would be sufficient to displace 23% of
      electricity generated from coal.

PMID- 19745150
TI  - Endogenous nitric oxide protects bacteria against a wide spectrum of antibiotics.
AB  - Bacterial nitric oxide synthases (bNOS) are present in many Gram-positive species
      and have been demonstrated to synthesize NO from arginine in vitro and in vivo.
      However, the physiological role of bNOS remains largely unknown. We show that NO
      generated by bNOS increases the resistance of bacteria to a broad spectrum of
      antibiotics, enabling the bacteria to survive and share habitats with antibiotic
      producing microorganisms. NO-mediated resistance is achieved through both the
      chemical modification of toxic compounds and the alleviation of the oxidative
      stress imposed by many antibiotics. Our results suggest that the inhibition of
      NOS activity may increase the effectiveness of antimicrobial therapy.

PMID- 19745151
TI  - A dimeric structure for archaeal box C/D small ribonucleoproteins.
AB  - Methylation of ribosomal RNA (rRNA) is required for optimal protein synthesis.
      Multiple 2'-O-ribose methylations are carried out by box C/D guide
      ribonucleoproteins [small ribonucleoproteins (sRNPs) and small nucleolar
      ribonucleoproteins (snoRNPs)], which are conserved from archaea to eukaryotes.
      Methylation is dictated by base pairing between the specific guide RNA component
      of the sRNP or snoRNP and the target rRNA. We determined the structure of a
      reconstituted and catalytically active box C/D sRNP from the archaeon
      Methanocaldococcus jannaschii by single-particle electron microscopy. We found
      that archaeal box C/D sRNPs unexpectedly formed a dimeric structure with an
      alternative organization of their RNA and protein components that challenges the
      conventional view of their architecture. Mutational analysis demonstrated that
      this di-sRNP structure was relevant for the enzymatic function of archaeal box
      C/D sRNPs.

PMID- 19745152
TI  - Tuned for transposition: molecular determinants underlying the hyperactivity of a
      Stowaway MITE.
AB  - Miniature inverted repeat transposable elements (MITEs) are widespread in
      eukaryotic genomes, where they can attain high copy numbers despite a lack of
      coding capacity. However, little is known about how they originate and amplify.
      We performed a genome-wide screen of functional interactions between Stowaway
      MITEs and potential transposases in the rice genome and identified a
      transpositionally active MITE that possesses key properties that enhance
      transposition. Although not directly related to its autonomous element, the MITE
      has less affinity for the transposase than does the autonomous element but lacks
      a motif repressing transposition in the autonomous element. The MITE contains
      internal sequences that enhance transposition. These findings suggest that MITEs
      achieve high transposition activity by scavenging transposases encoded by
      distantly related and self-restrained autonomous elements.

PMID- 19745153
TI  - The RNA-binding protein NANOS2 is required to maintain murine spermatogonial stem
      cells.
AB  - Stem cells give rise to differentiated cell types but also preserve their
      undifferentiated state through cell self-renewal. With the use of transgenic
      mice, we found that the RNA-binding protein NANOS2 is essential for maintaining
      spermatogonial stem cells. Lineage-tracing analyses revealed that
      undifferentiated spermatogonia expressing Nanos2 self-renew and generate the
      entire spermatogenic cell lineage. Conditional disruption of postnatal Nanos2
      depleted spermatogonial stem cell reserves, whereas mouse testes in which Nanos2
      had been overexpressed accumulated spermatogonia with undifferentiated, stem cell
      like properties. Thus, NANOS2 is a key stem cell regulator that is expressed in
      self-renewing spermatogonial stem cells and maintains the stem cell state during
      murine spermatogenesis.

PMID- 19745154
TI  - Activation of Rho GTPases by DOCK exchange factors is mediated by a nucleotide
      sensor.
AB  - Activation of Rho guanosine triphosphatases (GTPases) to the guanine triphosphate
      (GTP)-bound state is a critical event in their regulation of the cytoskeleton and
      cell signaling. Members of the DOCK family of guanine nucleotide exchange factors
      (GEFs) are important activators of Rho GTPases, but the mechanism of activation
      by their catalytic DHR2 domain is unknown. Through structural analysis of DOCK9
      Cdc42 complexes, we identify a nucleotide sensor within the alpha10 helix of the
      DHR2 domain that contributes to release of guanine diphosphate (GDP) and then to
      discharge of the activated GTP-bound Cdc42. Magnesium exclusion, a critical
      factor in promoting GDP release, is mediated by a conserved valine residue within
      this sensor, whereas binding of GTP-Mg2+ to the nucleotide-free complex results
      in magnesium-inducing displacement of the sensor to stimulate discharge of Cdc42
      GTP. These studies identify an unusual mechanism of GDP release and define the
      complete GEF catalytic cycle from GDP dissociation followed by GTP binding and
      discharge of the activated GTPase.

PMID- 19745155
TI  - A G protein-coupled receptor is essential for Schwann cells to initiate
      myelination.
AB  - The myelin sheath allows axons to conduct action potentials rapidly in the
      vertebrate nervous system. Axonal signals activate expression of specific
      transcription factors, including Oct6 and Krox20, that initiate myelination in
      Schwann cells. Elevation of cyclic adenosine monophosphate (cAMP) can mimic
      axonal contact in vitro, but the mechanisms that regulate cAMP levels in vivo are
      unknown. Using mutational analysis in zebrafish, we found that the G protein
      coupled receptor Gpr126 is required autonomously in Schwann cells for
      myelination. In gpr126 mutants, Schwann cells failed to express oct6 and krox20
      and were arrested at the promyelinating stage. Elevation of cAMP in gpr126
      mutants, but not krox20 mutants, could restore myelination. We propose that
      Gpr126 drives the differentiation of promyelinating Schwann cells by elevating
      cAMP levels, thereby triggering Oct6 expression and myelination.

PMID- 19745156
TI  - Energy-efficient action potentials in hippocampal mossy fibers.
AB  - Action potentials in nonmyelinated axons are considered to contribute
      substantially to activity-dependent brain metabolism. Here we show that fast Na+
      current decay and delayed K+ current onset during action potentials in
      nonmyelinated mossy fibers of the rat hippocampus minimize the overlap of their
      respective ion fluxes. This results in total Na+ influx and associated energy
      demand per action potential of only 1.3 times the theoretical minimum, in
      contrast to the factor of 4 used in previous energy budget calculations for
      neural activity. Analysis of ionic conductance parameters revealed that the
      properties of Na+ and K+ channels are matched to make axonal action potentials
      energy-efficient, minimizing their contribution to activity-dependent metabolism.

PMID- 19745158
TI  - Enhanced production of IL-17A during zymosan-induced peritonitis in obese mice.
AB  - IL-17A is a proinflammatory cytokine critical for host defense and involved in
      the pathogenesis of autoimmune disorders. Obesity is associated with chronic low
      grade inflammation but also with a heightened acute inflammatory response. We
      investigated the effect of obesity on IL-17A production using the model of ZY
      induced peritonitis. Compared with lean controls, administration of ZY induced a
      significantly exacerbated inflammatory response in obese leptin-deficient ob/ob
      mice and in mice with diet-induced obesity (DIO). Levels of IL-17A in the
      peritoneal fluid in response to ZY were elevated significantly in ob/ob and DIO
      mice compared with lean animals. Reconstitution of ob/ob mice with exogenous
      leptin did not alter production of IL-17A significantly in response to ZY.
      Peritoneal cells and adipose tissue obtained from ZY-injected obese mice
      expressed significantly higher levels of IL-17A mRNA compared with lean mice.
      Approximately 2% of peritoneal Ly6G(+) neutrophils from ZY-injected obese mice
      expressed IL-17A protein, compared with 0.2% of cells obtained from lean mice.
      Neutralization of IL-17 in ob/ob mice inhibited neutrophil recruitment and
      production of neutrophil-attracting CXC chemokines and IL-6, without affecting
      macrophage infiltration or levels of IL-10 and the chemokine CCL2. In contrast,
      neutralization of IL-6 did not affect production of IL-17A or chemokines while
      reducing production of the acute-phase protein serum amyloid A significantly.
      These data demonstrate that neutrophil-derived IL-17A is increased in obese mice
      during acute inflammation and contributes to exacerbation of inflammatory
      responses.

PMID- 19745159
TI  - ABC drug transporters and immunity: novel therapeutic targets in autoimmunity and
      cancer.
AB  - ABC transporters were identified originally for their contribution to clinical
      MDR as a result of their capacity to extrude various unrelated cytotoxic drugs.
      More recent reports have shown that ABC transporters can play important roles in
      the development, differentiation, and maturation of immune cells and are involved
      in migration of immune effector cells to sites of inflammation. Many of the
      currently identified, endogenous ABC transporter substrates have
      immunostimulating effects. Increasing the expression of ABC transporters on
      immune cells and thereby enhancing immune cell development or functionality may
      be beneficial to immunotherapy in the field of oncology. On the contrary, in the
      treatment of autoimmune diseases, blockade of these transporters may prove
      beneficial, as it could dampen disease activity by compromising immune effector
      cell functions. This review will focus on the expression, regulation, and
      substrate specificity of ABC transporters in relation to functional activities of
      immune effector cells and discusses implications for the treatment of cancer on
      the one hand and autoimmune diseases on the other.

PMID- 19745160
TI  - Trend tests for genetic association using population-based cross-sectional
      complex survey data.
AB  - Genetic data collected from surveys such as the Third National Health and
      Nutrition Examination Survey (NHANES III) enable researchers to investigate the
      association between wide varieties of health factors and genetic variation for
      the US population. Tests for trend in disease with increasing number of alleles
      have been developed for simple random samples. However, surveys such as the
      NHANES III have complex sample designs involving multistage cluster sampling and
      sample weighting. These types of sample designs can affect Type I error and power
      properties of statistical tests based on simple random samples. In order to
      address these issues, we have derived tests of trend based on Wald and quasi
      score statistics, with and without assuming a genetic model, that account for the
      complex sampling design. The finite-sample properties of the proposed test
      procedures are evaluated via Monte Carlo simulation studies. We make
      recommendations about the choice of the test statistic depending on whether or
      not the underlying genetic model is known. Proposed test statistics are applied
      to NHANES III data to test for associations between the locus ADRB2 (rs1042713)
      and obesity, between VDR (rs2239185) and high blood lead level, and between TGFB1
      (rs1982073) and asthma.

PMID- 19745161
TI  - Psychometric properties of the KPAS in diverse ethnic groups of midlife women.
AB  - The Kaiser Physical Activity Survey (KPAS), designed specifically for diverse
      activity domains (housework, caregiving, occupational activity), is used to
      assess physical activity among multiethnic midlife women. This study evaluates
      KPAS reliability and validity (not widely documented) in measuring physical
      activity among 341 groups in this classification. Internal consistency
      coefficients are adequate for all ethnic groups except non-Hispanic (N-H) African
      Americans. To evaluate construct validity, the researchers use multiple analytic
      approaches, including correlation between behavioral intention and KPAS scores
      and factor analysis. KPAS scores correlate positively with behavioral intention
      scores among all ethnic groups. Eight factors are extracted among all groups
      except N-H Asian Americans. In the convergent validity test, N-H African
      Americans and N-H Asian Americans show unique patterns. Overall, the KPAS proves
      reliable as a reasonably accurate instrument to assess physical activities among
      multiethnic groups of midlife women. However, cultural sensitivity among N-H
      African Americans and N-H Asian Americans needs further examination.

PMID- 19745162
TI  - Spontaneous calcium oscillations regulate human cardiac progenitor cell growth.
AB  - RATIONALE: The adult heart possesses a pool of progenitor cells stored in
      myocardial niches, but the mechanisms involved in the activation of this cell
      compartment are currently unknown. OBJECTIVE: Ca2+ promotes cell growth raising
      the possibility that changes in intracellular Ca2+ initiate division of c-kit
      positive human cardiac progenitor cells (hCPCs) and determine their fate. METHODS
      AND RESULTS: Ca2+ oscillations were identified in hCPCs and these events occurred
      independently from coupling with cardiomyocytes or the presence of extracellular
      Ca2+. These findings were confirmed in the heart of transgenic mice in which
      enhanced green fluorescent protein was under the control of the c-kit promoter.
      Ca2+ oscillations in hCPCs were regulated by the release of Ca2+ from the
      endoplasmic reticulum through activation of inositol 1,4,5-triphosphate receptors
      (IP3Rs) and the reuptake of Ca2+ by the sarco-/endoplasmic reticulum Ca2+ pump
      (SERCA). IP3Rs and SERCA were highly expressed in hCPCs, whereas ryanodine
      receptors were not detected. Although Na+-Ca2+ exchanger, store-operated Ca2+
      channels and plasma membrane Ca2+ pump were present and functional in hCPCs, they
      had no direct effects on Ca2+ oscillations. Conversely, Ca2+ oscillations and
      their frequency markedly increased with ATP and histamine which activated
      purinoceptors and histamine-1 receptors highly expressed in hCPCs. Importantly,
      Ca2+ oscillations in hCPCs were coupled with the entry of cells into the cell
      cycle and 5-bromodeoxyuridine incorporation. Induction of Ca2+ oscillations in
      hCPCs before their intramyocardial delivery to infarcted hearts was associated
      with enhanced engraftment and expansion of these cells promoting the generation
      of a large myocyte progeny. CONCLUSION: IP3R-mediated Ca2+ mobilization control
      hCPC growth and their regenerative potential.

PMID- 19745163
TI  - Shear stress inhibits homocysteine-induced stromal cell-derived factor-1
      expression in endothelial cells.
AB  - RATIONALE: Hyperhomocysteinemia contributes to vascular dysfunction and risks of
      cardiovascular diseases. Stromal cell-derived factor (SDF)-1, a chemokine
      expressed by endothelial cells (ECs), is highly expressed in advanced
      atherosclerotic lesions. The interplays among homocysteine, chemokines, and shear
      stress in regulating vascular endothelial function are not clearly understood.
      OBJECTIVE: To investigate the mechanisms for modulations of EC SDF-1 expression
      by homocysteine and shear stress. METHODS AND RESULTS: Homocysteine stimulation
      induced dose- and time-dependent SDF-1 expression and phosphorylation of mitogen
      activated protein kinases extracellular signal-regulated kinase (ERK), c-Jun N
      terminal kinase (JNK), and p38. By using specific inhibitors, small interfering
      (si)RNA, and dominant negative mutants, we demonstrated that activation of JNK
      pathway is critical for the homocysteine-induced SDF-1 expression. Transcription
      factor ELISA and chromatin immunoprecipitation assays showed that homocysteine
      increased Sp1- and AP-1-DNA binding activities in ECs. Inhibition of Sp1 and AP-1
      activations by specific siRNA blocked the homocysteine-induced SDF-1 promoter
      activity and expression. Preshearing of ECs for 1 to 4 hours at 20 dyn/cm2
      inhibited the homocysteine-induced JNK phosphorylation, Sp1 and AP-1 activation,
      and SDF-1 expression. The homocysteine-induced SDF-1 expression was suppressed by
      NO donor. Inhibitor or siRNA for endothelial NO synthase abolished the shear
      inhibition of SDF-1 expression. CONCLUSIONS: Our findings serve to elucidate the
      molecular mechanisms underlying the homocysteine induction of SDF-1 expression in
      ECs and the shear stress protection against this induction.

PMID- 19745164
TI  - Tbx1 regulates proliferation and differentiation of multipotent heart
      progenitors.
AB  - RATIONALE: TBX1 encodes a T-box transcription factor implicated in DiGeorge
      syndrome, which affects the development of many organs, including the heart. Loss
      of Tbx1 results into hypoplasia of heart regions derived from the second heart
      field, a population of cardiac progenitors cells (CPCs). Thus, we hypothesized
      that Tbx1 is an important player in the biology of CPCs. OBJECTIVE: We asked
      whether Tbx1 is expressed in multipotent CPCs and, if so, what role it may play
      in them. METHODS AND RESULTS: We used clonal analysis of Tbx1-expressing cells
      and loss and gain of function models, in vivo and in vitro, to define the role of
      Tbx1 in CPCs. We found that Tbx1 is expressed in multipotent heart progenitors
      that, in clonal assays, can give rise to 3 heart lineages expressing endothelial,
      smooth muscle and cardiomyocyte markers. In multipotent cells, Tbx1 stimulates
      proliferation, explaining why Tbx1(-/-) embryos have reduced proliferation in the
      second heart field. In this population, Tbx1 is expressed while cells are
      undifferentiated and it disappears with the onset of muscle markers. Loss of Tbx1
      results in premature differentiation, whereas gain results in reduced
      differentiation in vivo. We found that Tbx1 binds serum response factor, a master
      regulator of muscle differentiation, and negatively regulates its level.
      CONCLUSIONS: The Tbx1 protein marks CPCs, supports their proliferation, and
      inhibits their differentiation. We propose that Tbx1 is a key regulator of CPC
      homeostasis as it modulates positively their proliferation and negatively their
      differentiation.

PMID- 19745165
TI  - A role of matrix metalloproteinase-8 in atherosclerosis.
AB  - RATIONALE: Atherosclerotic lesions express matrix metalloproteinase (MMP)8, which
      possesses proteolytic activity on matrix proteins particularly fibrillar
      collagens and on nonmatrix proteins such as angiotensin (Ang) I. OBJECTIVE: We
      studied whether MMP8 plays a role in atherogenesis. METHODS AND RESULTS: In
      atherosclerosis-prone apolipoprotein E-deficient mice, inactivating MMP8 resulted
      in a substantial reduction in atherosclerotic lesion formation.
      Immunohistochemical examinations showed that atherosclerotic lesions in MMP8
      deficient mice had significantly fewer macrophages but increased collagen
      content. In line with results of in vitro assays showing that Ang I cleavage by
      MMP8 generated Ang II, MMP8 knockout mice had lower Ang II levels and lower blood
      pressure. In addition, we found that products of Ang I cleavage by MMP8 increased
      vascular cell adhesion molecule (VCAM)-1 expression and that MMP8-deficient mice
      had reduced VCAM-1 expression in atherosclerotic lesions. Intravital microscopy
      analysis showed that leukocyte rolling and adhesion on vascular endothelium was
      reduced in MMP8 knockout mice. Furthermore, we detected an association between
      MMP8 gene variation and extent of coronary atherosclerosis in patients with
      coronary artery disease. A relationship among MMP8 gene variation, plasma VCAM-1
      level, and atherosclerosis progression was also observed in a population-based,
      prospective study. CONCLUSIONS: These results indicate that MMP8 is an important
      player in atherosclerosis.

PMID- 19745166
TI  - Decreased expression and activity of cAMP phosphodiesterases in cardiac
      hypertrophy and its impact on beta-adrenergic cAMP signals.
AB  - RATIONALE: Multiple cyclic nucleotide phosphodiesterases (PDEs) degrade cAMP in
      cardiomyocytes but the role of PDEs in controlling cAMP signaling during
      pathological cardiac hypertrophy is poorly defined. OBJECTIVE: Evaluate the beta
      adrenergic regulation of cardiac contractility and characterize the changes in
      cardiomyocyte cAMP signals and cAMP-PDE expression and activity following cardiac
      hypertrophy. METHODS AND RESULTS: Cardiac hypertrophy was induced in rats by
      thoracic aortic banding over a time period of 5 weeks and was confirmed by
      anatomic measurements and echocardiography. Ex vivo myocardial function was
      evaluated in Langendorff-perfused hearts. Engineered cyclic nucleotide-gated
      (CNG) channels were expressed in single cardiomyocytes to monitor subsarcolemmal
      cAMP using whole-cell patch-clamp recordings of the associated CNG current
      (I(CNG)). PDE variant activity and protein level were determined in purified
      cardiomyocytes. Aortic stenosis rats exhibited a 67% increase in heart weight
      compared to sham-operated animals. The inotropic response to maximal beta
      adrenergic stimulation was reduced by approximately 54% in isolated hypertrophied
      hearts, along with a approximately 32% decrease in subsarcolemmal cAMP levels in
      hypertrophied myocytes. Total cAMP hydrolytic activity as well as PDE3 and PDE4
      activities were reduced in hypertrophied myocytes, because of a reduction of
      PDE3A, PDE4A, and PDE4B, whereas PDE4D was unchanged. Regulation of beta
      adrenergic cAMP signals by PDEs was blunted in hypertrophied myocytes, as
      demonstrated by the diminished effects of IBMX (100 micromol/L) and of both the
      PDE3 inhibitor cilostamide (1 micromol/L) and the PDE4 inhibitor Ro 201724 (10
      micromol/L). CONCLUSIONS: Beta-adrenergic desensitization is accompanied by a
      reduction in cAMP-PDE and an altered modulation of beta-adrenergic cAMP signals
      in cardiac hypertrophy.

PMID- 19745167
TI  - Dual pathways of carbon monoxide-mediated vasoregulation: modulation by redox
      mechanisms.
AB  - RATIONALE: Vascular tissues produce carbon monoxide (CO) via HO-dependent and HO
      independent mechanisms; the former in tandem with biliverdin and iron and the
      latter as a lone product. CO has been shown to function as both a vasoconstrictor
      and vasodilator; however, factors that dictate the vasoregulatory phenotype of
      this gas are unknown. OBJECTIVE: We investigated whether CO-mediated
      vasoconstriction is mechanistically linked to enhanced reactive oxygen species
      production that masks vasodilatory pathways. METHODS AND RESULTS: Sprague-Dawley
      rat interlobar and interlobular arteries were examined in terms of superoxide
      (O2*-) generation and vascular reactivity in the absence and presence of
      antioxidants. Both authentic CO and the CO-releasing molecule (CORM)-3
      constricted renal arteries and increased O2*- production in a dose-dependent
      manner. The antioxidants tempol, ebselen, and deferoxamine inhibited CO-induced
      O2*- production and converted CO from constrictor to dilator. CO-induced O2*-
      generation was found to involve the activity of multiple oxidases including
      nitric oxide synthase, NADPH oxidase, xanthine oxidase, and complex IV of the
      mitochondrial electron chain. Furthermore, inhibition of these enzymes converted
      CO from constrictor to dilator. Similarly, biliverdin and bilirubin inhibited CO
      induced O2*- production and vasoconstriction, allowing for a vasodilatory
      response to CO to be expressed. CO-induced vasoconstriction was dependent on a
      non-thromboxane agonist of the thromboxane receptor, whereas vasodilatory
      mechanisms of CO relied on the activation of soluble guanylate cyclase and
      calcium-gated potassium channels. CONCLUSIONS: CO-induced vasoconstriction
      involves the generation of reactive oxygen species, which, when negated, allows
      for the expression of vasodilatory pathways which are masked by the primary
      oxidative stress response to this gas.

PMID- 19745168
TI  - Cardiac Na+ current regulation by pyridine nucleotides.
AB  - RATIONALE: Mutations in glycerol-3-phosphate dehydrogenase 1-like (GPD1-L)
      protein reduce cardiac Na+ current (I(Na)) and cause Brugada Syndrome (BrS). GPD1
      L has >80% amino acid homology with glycerol-3-phosphate dehydrogenase, which is
      involved in NAD-dependent energy metabolism. OBJECTIVE: Therefore, we tested
      whether NAD(H) could regulate human cardiac sodium channels (Na(v)1.5). METHODS
      AND RESULTS: HEK293 cells stably expressing Na(v)1.5 and rat neonatal
      cardiomyocytes were used. The influence of NADH/NAD+ on arrhythmic risk was
      evaluated in wild-type or SCN5A(+/-) mouse heart. A280V GPD1-L caused a 2.48+/
      0.17-fold increase in intracellular NADH level (P<0.001). NADH application or
      cotransfection with A280V GPD1-L resulted in decreased I(Na) (0.48+/-0.09 or
      0.19+/-0.04 of control group, respectively; P<0.01), which was reversed by NAD+,
      chelerythrine, or superoxide dismutase. NAD+ antagonism of the Na+ channel
      downregulation by A280V GPD1-L or NADH was prevented by a protein kinase (PK)A
      inhibitor, PKAI(6-22). The effects of NADH and NAD+ were mimicked by a phorbol
      ester and forskolin, respectively. Increasing intracellular NADH was associated
      with an increased risk of ventricular tachycardia in wild-type mouse hearts.
      Extracellular application of NAD+ to SCN5A(+/-) mouse hearts ameliorated the risk
      of ventricular tachycardia. CONCLUSIONS: Our results show that Na(v)1.5 is
      regulated by pyridine nucleotides, suggesting a link between metabolism and
      I(Na). This effect required protein kinase C activation and was mediated by
      oxidative stress. NAD+ could prevent this effect by activating PKA. Mutations of
      GPD1-L may downregulate Na(v)1.5 by altering the oxidized to reduced NAD(H)
      balance.

PMID- 19745169
TI  - Role of the lysine-specific demethylase 1 in the proinflammatory phenotype of
      vascular smooth muscle cells of diabetic mice: retraction.

PMID- 19745171
TI  - NCX1 expression and functional activity increase in microglia invading the
      infarct core.
AB  - BACKGROUND AND PURPOSE: The sodium-calcium exchanger NCX1 represents a key
      mediator for maintaining [Na(+)](i) and [Ca(2+)](i) in anoxic conditions. To
      date, no information is available on NCX1 protein expression and activity in
      microglial cells under ischemic conditions. METHODS: By means of Western
      blotting, patch-clamp electrophysiology, single-cell Fura-2 acetoxymethyl-ester
      microfluorometry, immunohistochemistry, and confocal microscopy, we investigated
      the regional and temporal changes of NCX1 protein in microglial cells of the peri
      infarct and core regions after permanent middle cerebral artery occlusion. The
      exchanger expression and activity were measured in primary microglia isolated ex
      vivo from the core region of adult rat brains 7 days after permanent middle
      cerebral artery occlusion and in cultured microglia under in vitro hypoxia.
      RESULTS: One day after permanent middle cerebral artery occlusion, NCX1 protein
      expression was detected in some microglial cells adjacent to the soma of neurons
      in the infarct core. More interestingly, 3 and 7 days after permanent middle
      cerebral artery occlusion, NCX1 signal strongly increased in the round-shaped
      microglia invading the infarct core. Cultured microglial cells obtained from the
      core also displayed increased NCX1 expression as compared with contralateral
      cells and showed enhanced NCX activity in the reverse mode of operation.
      Similarly, NCX activity and NCX1 protein expression were significantly enhanced
      in BV2 microglia exposed to oxygen and glucose deprivation, whereas NCX2 and NCX3
      were downregulated. Interestingly, in NCX1-silenced cells, [Ca(2+)](i) increase
      induced by hypoxia was completely prevented. Conclusion- The upregulation of NCX1
      expression and activity observed in microglia after permanent middle cerebral
      artery occlusion suggests a relevant role of NCX1 in modulating microglia
      functions in the postischemic brain.

PMID- 19745170
TI  - Cardiovascular consequences when nitric oxide and lipid signaling converge.
AB  - The identification of nitric oxide ((*)NO) as an endogenously produced free
      radical mediator of endothelial-dependent relaxation and host defense has
      fundamentally changed concepts of cell signal transduction. Ligand-receptor
      oriented paradigms of cell signaling were originally centered on the concept of a
      high affinity and specific interaction between a ligand and its receptor,
      resulting in the activation of secondary signaling events such as gene expression
      or modulation of catalytic protein function. While (*)NO ligation of the heme
      iron of soluble guanylate cyclase is consistent with this perspective, the
      readily diffusible and broadly reactive (*)NO is increasingly appreciated to
      react with a vast array of target molecules that mediate paracrine vasodilator
      actions, inhibition of thrombosis and neointimal proliferation, and both pro- and
      antiinflammatory signaling reactions that are not affected by inhibitors of
      soluble guanylate cyclase. There is an expanding array of functionally
      significant "off target" collateral reactions mediated by (*)NO that are
      guanylate cyclase-independent and rather are dictated by anatomic distribution
      and the formation of secondary (*)NO-derived species. These reactions are a
      critical element of redox-regulated signaling and are addressed herein in the
      context of the oxidation of unsaturated fatty acids to vascular and inflammatory
      signaling mediators. Because of their abundance and the intrinsic reactivity of
      unsaturated lipid intermediates and eicosanoid metabolism enzymes with (*)NO and
      other oxides of nitrogen, lipid signaling mechanisms are a significant target for
      regulation by (*)NO in the vascular compartment. This convergence of (*)NO and
      lipid signaling pathways thus adds another level of regulation to physiological
      responses such as vasodilation, thrombosis, and inflammation. Herein,
      interactions between (*)NO and lipid signaling events are placed in the context
      of cardiovascular regulation.

PMID- 19745172
TI  - Statin treatment and stroke outcome in the Stroke Prevention by Aggressive
      Reduction in Cholesterol Levels (SPARCL) trial.
AB  - BACKGROUND AND PURPOSE: Laboratory experiments suggest statins reduce stroke
      severity and improve outcomes. The Stroke Prevention by Aggressive Reduction in
      Cholesterol Levels (SPARCL) trial was a placebo-controlled, randomized trial
      designed to determine whether treatment with atorvastatin reduces strokes in
      subjects with recent stroke or transient ischemic attack (n=4731). We analyzed
      SPARCL trial data to determine whether treatment favorably shifts the
      distribution of severities of ischemic cerebrovascular outcomes. METHODS:
      Severity was assessed with the National Institutes of Health Stroke Scale,
      Barthel Index, and modified Rankin Scale score at enrollment (1 to 6 months after
      the index event) and 90 days poststroke in subjects having a stroke during the
      trial. RESULTS: Over 4.9 years, strokes occurred in 576 subjects. There were
      reductions in fatal, severe (modified Rankin Scale score 5 or 4), moderate
      (modified Rankin Scale score 3 or 2), and mild (modified Rankin Scale score 1 or
      0) outcome ischemic strokes and transient ischemic attacks and an increase in the
      proportion of event-free subjects randomized to atorvastatin (P<0.001 unadjusted
      and adjusted). Results were similar for all outcome events (ischemic and
      hemorrhagic, P<0.001 unadjusted and adjusted) with no effect on outcome
      hemorrhagic stroke severity (P=0.174 unadjusted, P=0.218 adjusted). If the
      analysis is restricted to those having an outcome ischemic stroke (ie, excluding
      those having a transient ischemic attack or no event), there was only a trend
      toward lesser severity with treatment based on the modified Rankin Scale score
      (P=0.0647) with no difference based on the National Institutes of Health Stroke
      Scale or Barthel Index. CONCLUSIONS: The present exploratory analysis suggests
      that the outcome of recurrent ischemic cerebrovascular events might be improved
      among statin users as compared with nonusers.

PMID- 19745173
TI  - Diagnostic usefulness of the ABCD2 score to distinguish transient ischemic attack
      and minor ischemic stroke from noncerebrovascular events: the North Dublin TIA
      Study.
AB  - BACKGROUND AND PURPOSE: Transient ischemic attack (TIA) diagnosis is frequently
      difficult in clinical practice. Noncerebrovascular symptoms are often
      misclassified as TIA by nonspecialist physicians. Clinical prediction rules such
      as ABCD(2) improve the identification of patients with TIA at high risk of early
      stroke. We hypothesized that the ABCD(2) score may partly improve risk
      stratification due to improved discrimination of true TIA and minor ischemic
      stroke (MIS) from noncerebrovascular events. METHODS: Consecutive patients with
      TIA were identified within a prospective population-based cohort study of stroke
      and TIA. The cohort was expanded by inclusion of patients with MIS and
      noncerebrovascular events referred to a daily TIA clinic serving the population.
      Diagnosis was assigned by a trained stroke physician independent of ABCD(2)
      score. RESULTS: Five hundred ninety-four patients were included (292 [49.2%] TIA,
      45 [7.6%] MIS, and 257 [43.3%] noncerebrovascular). The mean ABCD(2) score showed
      a graded increase across diagnostic groups (MIS mean 4.8 [SD 1.4] versus TIA mean
      3.9 [SD 1.5] versus noncerebrovascular mean 2.9 [SD 1.5]; P<0.00001). The ABCD(2)
      score discriminated well between noncerebrovascular and cerebrovascular events
      TIA (c-statistic 0.68; 95% CI, 0.64 to 0.72), any vascular event (TIA+MIS; c
      statistic 0.7; 95% CI, 0.66 to 0.74), and MIS (c-statistic 0.81; 95% CI, 0.75 to
      0.87)-from noncerebrovascular events. Of ABCD(2) items, unilateral weakness (OR,
      4.5; 95% CI, 3.1 to 6.6) and speech disturbance (OR, 2.5; 95% CI, 1.6, 4.1) were
      most likely overrepresented in TIA compared with noncerebrovascular groups.
      CONCLUSIONS: The ABCD(2) score had significant diagnostic usefulness for
      discrimination of true TIA and MIS from noncerebrovascular events, which may
      contribute to its predictive usefulness.

PMID- 19745174
TI  - Pitfalls in meta-analysis of observational studies: lessons from a systematic
      review of the risks of stenting for intracranial atherosclerosis.

PMID- 19745175
TI  - Effects of moderate-dose omega-3 fish oil on cardiovascular risk factors and mood
      after ischemic stroke: a randomized, controlled trial.
AB  - BACKGROUND AND PURPOSE: Fish-derived omega-3 fatty acids have long been
      associated with cardiovascular protection. In this trial, we assessed whether
      treatment with a guideline-recommended moderate-dose fish oil supplement could
      improve cardiovascular biomarkers, mood- and health-related quality of life in
      patients with ischemic stroke. METHODS: Patients with CT-confirmed stroke were
      randomized to 3 g/day encapsulated fish oil containing approximately 1.2 g total
      omega-3 (0.7 g docosahexaenoic acid; 0.3 g eicosapentaenoic acid) or placebo oil
      (combination palm and soy) taken daily over 12 weeks. Serum triglycerides, total
      cholesterol and associated lipoproteins, selected inflammatory and hemostatic
      markers, mood, and health-related quality of life were assessed at baseline and
      follow-up. The primary outcome was change in triglycerides. Compliance was
      assessed by capsule count and serum phospholipid omega-3 levels (Australian
      Clinical Trials Registration: ACTRN12605000207617). RESULTS: One hundred two
      patients were randomized to fish oil or placebo. Intention-to-treat and per
      protocol (>85% compliance) analyses showed no significant effect of fish oil
      treatment on any lipid, inflammatory, hemostatic, or composite mood parameters
      measured. Adherence to treatment based on pill count was good (89%) reflected by
      increased serum docosahexanoic acid (P<0.001) and eicosapentaenoic acid
      (P=0.0006) in the fish oil group. Analysis of oil composition, however, showed
      some degradation and potentially adverse oxidation products at the end of the
      study. CONCLUSIONS: There was no effect of 12 weeks of treatment with moderate
      dose fish oil supplements on cardiovascular biomarkers or mood in patients with
      ischemic stroke. It is possible that insufficient dose, short duration of
      treatment, and/or oxidation of the fish oils may have influenced these outcomes.

PMID- 19745177
TI  - World Stroke Day 2009: what can I do?

PMID- 19745176
TI  - A randomized, double-blind, placebo-controlled trial to evaluate the efficacy,
      safety, tolerability, and pharmacokinetic/pharmacodynamic effects of a targeted
      exposure of intravenous repinotan in patients with acute ischemic stroke:
      modified Randomized Exposure Controlled Trial (mRECT).
AB  - BACKGROUND AND PURPOSE: Repinotan hydrochloride is a serotonin (5-HT)(1A)
      receptor full agonist with evidence of neuroprotection in animal models of
      permanent and transient focal ischemia. The purpose of this Phase IIb study was
      to investigate the efficacy, safety, and tolerability of a targeted exposure to
      repinotan in patients with acute ischemic stroke. METHODS: This was a double
      blind, placebo-controlled, parallel-group, multicenter study of 681 patients
      stratified according to whether or not tissue plasminogen activator was
      administered and then randomly assigned to treatment with repinotan or placebo. A
      continuous 72-hour intravenous infusion of repinotan or placebo was to be started
      within 4.5 hours from the onset of ischemic symptoms. A Point-of-Care test was
      used to adjust the infusion rate if appropriate. The goal of Modified Randomized
      Exposure Controlled Trial (mRECT) was to show whether repinotan is statistically
      superior to placebo (alpha <or= 0.10) as measured by the response rate on the
      primary efficacy variable, Barthel Index (>or=85) at 3 months, using a Cochran
      Mantel-Haenszel test. RESULTS: For the intention-to-treat population at 3 months,
      the response rate on the Barthel Index was 37.1% (127 of 342) for patients on
      repinotan and 42.4% (143 of 337) for patients taking the placebo (Cochran-Mantel
      Haenszel probability value=0.149). No apparent safety concerns were identified.
      CONCLUSIONS: mRECT demonstrated the feasibility of conducting a rigorous trial
      using a short therapeutic window demanding clinical and radiographic criteria to
      optimize patient selection and a Point-of-Care test to achieve a targeted
      exposure to repinotan. The study failed to demonstrate a clinical benefit of
      repinotan. The development of repinotan in acute ischemic stroke was
      discontinued.

PMID- 19745178
TI  - Statins prevent stroke recurrences...but can they improve stroke outcome?

PMID- 19745179
TI  - Attenuation of brain response to vascular endothelial growth factor-mediated
      angiogenesis and neurogenesis in aged mice.
AB  - BACKGROUND AND PURPOSE: Alterations of neuroangiogenic response play important
      roles in the development of aging-related neurodisorders and affect gene-based
      therapies. We tested brain response to vascular endothelial growth factor (VEGF)
      in aged mice. METHODS: Adeno-associated viral vector (AAV)-VEGF, an adeno
      associated viral vector expressing VEGF, was injected into the brain of 3-, 12-,
      and 24-month-old mice. AAV-LacZ-injected mice were used as controls (n=6). Before
      euthanasia at 6 weeks after vector injection, the mice were intraperitoneally
      injected with 5-bromodeoxyuridine for 3 consecutive days. The vascular density
      and the number of neuroprogenitors were analyzed. RESULTS: Injection of AAV-VEGF
      increased the vascular density in the brain of 3-, 12-, and 24-month-old mice by
      22%+/-7% (AAV-VEGF: 320+/-15 per 10x field versus AAV-LacZ: 263+/-8, P<0.05),
      20%+/-8 (AAV-VEGF: 300+/-9 versus AAV-LacZ: 250+/-11, P<0.05), and 7%+/-16% (AAV
      VEGF: 257+/-27 versus AAV-LacZ: 236+/-13, P=0.283), respectively. There were more
      VEGF receptor-positive neuroprogenitors in the subventricular zone of AAV-VEGF
      injected 3- (22+/-2) and 12-month-old mice (21+/-5) than that of 24-month-old
      mice (7+/-1). More 5-bromodeoxyuridine-positive endothelial cells and
      neuroprogenitors were detected around the injection site and subventricular zone
      of 3- (13+/-4) and 12-month-old mice (14+/-5) than that of 24-month-old mice (1+/
      1). VEGF receptor 2 was upregulated in AAV-VEGF-injected brains of 3- and 12
      month-old mice, but not in 24-month-old mice. CONCLUSIONS: The angiogenic and
      neurogenic response to VEGF stimulation is attenuated in the aged mouse brain,
      which may be due to reduced VEGF receptor activity.

PMID- 19745180
TI  - Pharmacologic interventions for stroke: looking beyond the thrombolysis time
      window into the penumbra with biomarkers, not a stopwatch.
AB  - BACKGROUND AND PURPOSE: The majority of pharmacological agents for stroke were
      developed based on the assumption that neurological deficits will be reduced upon
      the successful interruption of biochemical mechanisms leading to neuronal death.
      Despite significant evidence of preclinical efficacy, none of these agents
      succeeded. They either failed to demonstrate efficacy in the clinic or their
      development was halted for safety, strategic, or commercial reasons. SUMMARY OF
      REVIEW: This "neuroprotection strategy" has focused primarily on targets in the
      neurotoxic environment that occurs under ischemic conditions. In many cases,
      these agents were designed to tackle events that are known to start almost
      immediately after onset of ischemia, which is far before a realistic therapeutic
      time window opens for most, if not all, patients with stroke. In other instances,
      they were evaluated beyond a realistic timeframe in which one could expect
      significant salvageable tissue or penumbra to exist. Surprisingly, most of these
      agents were not evaluated in conjunction with strategies for improving perfusion
      to the affected tissue, indicating an overoptimistic assumption that
      neuroprotection alone could be sufficient to halt injury caused by an abrupt
      interruption of brain blood flow. CONCLUSIONS: We provide a constructive
      translational medicine perspective about how one could improve the drug
      development process with the hope that the probability for success can increase
      in our quest to establish a novel therapy for stroke.

PMID- 19745181
TI  - Intravenous tissue plasminogen activator in patients with cocaine-associated
      acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: The safety of thrombolytic therapy in patients with
      cocaine-associated acute ischemic stroke (CIS) is unknown. METHODS: We conducted
      a retrospective review of patients with CIS who presented to our stroke center.
      Thrombolytic treatment was compared between cocaine-positive (n=29) and cocaine
      negative (n=75) patients. We also compared patients with CIS treated with tissue
      plasminogen activator versus those who did not receive tissue plasminogen
      activator (n=58). Safety outcomes were determined by the incidence of symptomatic
      intracerebral hemorrhage, in-hospital mortality, and modified Rankin Scale at
      hospital discharge. RESULTS: There were no complications in tissue plasminogen
      activator-treated patients with CIS. Cocaine-positive and cocaine-negative
      treated patients had similar stroke severity and safety outcomes. Patients with
      CIS treated with tissue plasminogen activator had more severe strokes on baseline
      National Institutes of Health Stroke Scale but similar safety outcomes compared
      with nontreated patients with CIS. CONCLUSIONS: Thrombolytic therapy for CIS
      appears to be safe in this small study. Further research is needed to more
      definitively assess safety and efficacy of tissue plasminogen activator for CIS.

PMID- 19745182
TI  - Ischemic stroke in ethnic South Asians.

PMID- 19745183
TI  - Compliance with and use of up-to-date National Academies of Medical Dispatch
      Medical Priority Dispatch System protocols in dispatch practice and research
      studies must be a requirement.

PMID- 19745184
TI  - The therapeutic time window related to the presenting symptom pattern, that is,
      stable versus unstable patients, can affect the adverse event rate of
      intracranial stenting.

PMID- 19745185
TI  - Microgravity decreases and hypergravity increases exhaled nitric oxide.
AB  - Inhalation of toxic dust during planetary space missions may cause airway
      inflammation, which can be monitored with exhaled nitric oxide (NO). Gravity will
      differ from earth, and we hypothesized that gravity changes would influence
      exhaled NO by altering lung diffusing capacity and alveolar uptake of NO. Five
      subjects were studied during microgravity aboard the International Space Station,
      and 10 subjects were studied during hypergravity in a human centrifuge. Exhaled
      NO concentrations were measured during flows of 50 (all gravity conditions), 100,
      200, and 500 ml/s (hypergravity). During microgravity, exhaled NO fell from a
      ground control value of 12.3 +/- 4.7 parts/billion (mean +/- SD) to 6.6 +/- 4.4
      parts/billion (P = 0.016). In the centrifuge experiments and at the same flow,
      exhaled NO values were 16.0 +/- 4.3, 19.5 +/- 5.1, and 18.6 +/- 4.7 parts/billion
      at one, two, and three times normal gravity, where exhaled NO in hypergravity was
      significantly elevated compared with normal gravity (P <or= 0.011 for all flows).
      Estimated alveolar NO was 2.3 +/- 1.1 parts/billion in normal gravity and
      increased significantly to 3.9 +/- 1.4 and 3.8 +/- 0.8 parts/billion at two and
      three times normal gravity (P < 0.002). The findings of decreased exhaled NO in
      microgravity and increased exhaled and estimated alveolar NO values in
      hypergravity suggest that gravity-induced changes in alveolar-to-lung capillary
      gas transfer modify exhaled NO.

PMID- 19745186
TI  - Micro-opioid receptor agonist injections into the presumed pre-Botzinger complex
      and the surrounding region of awake goats do not alter eupneic breathing.
AB  - Opioids are clinically important in the alleviation of pain. An undesirable side
      effect of opioids is depression of breathing. Data from isolated preparations
      suggest this effect is due to attenuation of discharge activity of neurons in the
      pre-Botzinger complex (preBotzC), a medullary area with respiratory rhythmogenic
      properties. The purpose of this study was to examine how [d-Ala(2),N-Me
      Phe(4),Gly(5)-ol]-enkephalin (DAMGO), a mu-opioid receptor agonist, affected
      breathing after injection into the presumed preBotzC of the adult awake goat. We
      hypothesized that DAMGO would cause breathing to decrease and become irregular
      when injected into the presumed preBotzC and the surrounding region of the
      conscious animal. We further hypothesized that ventilatory sensitivity to CO(2)
      and hypoxia would be blunted after the injection of DAMGO. Microtubules were
      bilaterally implanted into the presumed preBotzC of 10 adult female goats. After
      recovery from the surgery, DAMGO (0.5-10 mul, 1 nM-10 muM) was injected into the
      presumed preBotzC during the awake state. DAMGO had no effect on pulmonary
      ventilation [inspiratory minute ventilation (Vi)], respiratory rhythm and
      pattern, the activation pattern of inspiratory and expiratory muscles, or
      arterial blood gases during eupneic breathing conditions (P > 0.10). However,
      DAMGO attenuated (P < 0.05) the evoked increase in breathing frequency when
      inspired CO(2) was increased, and DAMGO attenuated the Vi response to reduction
      of inspired O(2) to 10.8% (P < 0.05). We conclude that our data do not provide
      support for the concept that in awake mammals opioid depression of breathing is
      due to a directed action of opioids on preBotzC neurons.

PMID- 19745187
TI  - Estrogen and HRT promote a proanabolic skeletal muscle environment in older
      women.

PMID- 19745188
TI  - Roles of nitric oxide synthase isoforms in cutaneous vasodilation induced by
      local warming of the skin and whole body heat stress in humans.
AB  - Nitric oxide (NO) participates in the cutaneous vasodilation caused by increased
      local skin temperature (Tloc) and whole body heat stress in humans. In forearm
      skin, endothelial NO synthase (eNOS) participates in vasodilation due to elevated
      Tloc and neuronal NO synthase (nNOS) participates in vasodilation due to heat
      stress. To explore the relative roles and interactions of these isoforms, we
      examined the effects of a relatively specific eNOS inhibitor, N(omega)-amino-l
      arginine (LNAA), and a specific nNOS inhibitor, N(omega)-propyl-l-arginine
      (NPLA), both separately and in combination, on skin blood flow (SkBF) responses
      to increased Tloc and heat stress in two protocols. In each protocol, SkBF was
      monitored by laser-Doppler flowmetry (LDF) and mean arterial pressure (MAP) by
      Finapres. Cutaneous vascular conductance (CVC) was calculated (CVC = LDF/MAP).
      Intradermal microdialysis was used to treat one site with 5 mM LNAA, another with
      5 mM NPLA, a third with combined 5 mM LNAA and 5 mM NPLA (Mix), and a fourth site
      with Ringer only. In protocol 1, Tloc was controlled with combined LDF/local
      heating units. Tloc was increased from 34 degrees C to 41.5 degrees C to cause
      local vasodilation. In protocol 2, after a period of normothermia, whole body
      heat stress was induced (water-perfused suits). At the end of each protocol, all
      sites were perfused with 58 mM nitroprusside to effect maximal vasodilation for
      data normalization. In protocol 1, at Tloc = 34 degrees C, CVC did not differ
      between sites (P > 0.05). LNAA and Mix attenuated CVC increases at Tloc = 41.5
      degrees C to similar extents (P < 0.05, LNAA or Mix vs. untreated or NPLA). In
      protocol 2, in normothermia, CVC did not differ between sites (P > 0.05). During
      heat stress, NPLA and Mix attenuated CVC increases to similar extents, but no
      significant attenuation occurred with LNAA (P < 0.05, NPLA or Mix vs. untreated
      or LNAA). In forearm skin, eNOS mediates the vasodilator response to increased
      Tloc and nNOS mediates the vasodilator response to heat stress. The two isoforms
      do not appear to interact during either response.

PMID- 19745189
TI  - Effect of nandrolone decanoate administration on recovery from bupivacaine
      induced muscle injury.
AB  - Although testosterone administration elicits well-documented anabolic effects on
      skeletal muscle mass, the enhancement of muscle regeneration after injury has not
      been widely examined. The purpose of this study was to determine whether anabolic
      steroid administration improves skeletal muscle regeneration from bupivacaine
      induced injury. Male C57BL/6 mice were castrated 2 wk before muscle injury
      induced by an intramuscular bupivacaine injection into the tibialis anterior (TA)
      muscle. Control mice received an intramuscular PBS injection. Anabolic steroid
      [nandrolone decanoate (ND), 6 mg/kg] or sesame seed oil was administered at the
      time of initial injury and continued every 7 days for the study's duration. Mice
      were randomly assigned to one of four treatment groups for 5, 14, or 42 days of
      recovery, as follows: 1) control (uninjured); 2) ND only (uninjured + ND); 3)
      bupivacaine only (injured); or 4) bupivacaine + ND (injured + ND). TA morphology,
      protein, and gene expression were analyzed at 14 and 42 days after injury;
      protein expression was analyzed at 5 days after injury. After 14 days of
      recovery, the injury and injury + ND treatments induced small-diameter myofiber
      incidence and also decreased mean myofiber area. The increase in small-myofiber
      incidence was 65% greater in injury + ND muscle compared with injury alone. At 14
      days, injury + ND induced a fivefold increase in muscle IGF-I mRNA expression,
      which was greater than injury alone. Muscle Akt activity and glycogen synthetase
      kinase-3beta activity were also induced by injury + ND at 14 days of recovery,
      but not by injury alone. ND had a main effect for increasing muscle MyoD and
      cyclin D1 mRNA expression at 14 days. After 42 days of recovery, injury + ND
      increased large-diameter myofiber incidence compared with injury only. Nandrolone
      decanoate (ND) administration can enhance castrated mouse muscle regeneration
      during the recovery from bupivacaine-induced injury.

PMID- 19745190
TI  - Effects of the molecular mass of tense-state polymerized bovine hemoglobin on
      blood pressure and vasoconstriction.
AB  - Despite recent advances in the design of hemoglobin (Hb)-based oxygen carriers
      (HBOCs), vasoconstriction, presumably caused by nitric oxide (NO) scavenging,
      vessel wall hyperoxygenation, and/or extravasation, has been identified as the
      principal road block hampering commercial development of HBOCs. This study was
      designed to analyze systemic and microvascular responses to the molecular mass
      and plasma concentration of tense (T)-state polymerized bovine Hb (PolybHb)
      solutions. Experiments were performed using the hamster window chamber model
      subjected to successive hypervolemic infusions of T-state PolybHb solutions.
      PolybHb plasma concentrations were evaluated, namely, 0.5, 1.0 and 1.5 g/dl,
      respectively. Infusion of PolybHb solutions with molecular mass >500 kDa elicited
      hypertension and vasoconstriction proportional to the plasma concentration and
      inversely proportional to the PolybHb cross-link density. However, two high
      molecular mass PolybHb solutions, PolybHb(40:1)(high) PolybHb(50:1)(high), did
      not elicit vasoconstriction at all concentrations studied, whereas
      PolybHb(50:1)(high) only elicited moderate hypertension at the highest
      concentration studied. In contrast, infusion of PolybHb solutions with molecular
      mass <500 kDa elicited significant hypertension and vasoconstriction compared
      with PolybHb solutions with molecular mass >500 kDa that was proportional to the
      plasma concentration and inversely proportional to the PolybHb cross-link
      density. We present promising results for highly cross-linked T-state PolybHb
      solutions with molecular mass >500 kDa [PolybHb(40:1)(high) PolybHb(50:1)(high)],
      which supports the concept that HBOC size/molecular mass influences its proximity
      to the vascular endothelium and molecular diffusivity. The hemodynamics of HBOC
      within the plasma layer surrounding the abluminal side endothelium regulates NO
      production and consumption, vessel oxygen flux, and extravasation. Although
      mechanistically attractive, neither of these hypotheses can be directly tested in
      vivo and will require further investigation.

PMID- 19745191
TI  - Maturation of respiratory control and the propensity for breathing instability in
      a sheep model.
AB  - Limited evidence suggests that the ventilatory interaction between O(2) and CO(2)
      is additive after birth and becomes multiplicative with postnatal development.
      Such a switch may be linked to the propensity for periodic breathing (PB) in
      infancy. To test this idea, we characterized the maturation of the respiratory
      controller and its effect on breathing stability in approximately 10-day-old
      lambs and 6-mo-old sheep. We measured 1) carotid body sensitivity via dynamic
      ventilatory responses to step changes in O(2) and CO(2), 2) steady-state
      ventilatory sensitivity to CO(2) under hypoxic and hyperoxic conditions, 3) the
      dependence of the apneic threshold on arterial Po(2), and 4) the effect of
      hypoxic or hypercapnic gas inhalation during induced PB. Stability of the system
      was assessed using surrogate measures of loop gain. Peripheral sensitivity to
      O(2) was higher in newborn than in older animals (P < 0.05), but peripheral CO(2)
      sensitivity was unchanged. Central CO(2) sensitivity was reduced with age, but
      the slopes of the ventilatory responses to CO(2) were the same in hypoxia and
      hyperoxia. Reduced arterial Po(2) caused a leftward shift in the apneic threshold
      at both ages. Inspiration of hypoxic gas during PB immediately halted PB, whereas
      hypercapnia stopped PB only after one or two further PB cycles. We conclude that
      the controller in the sheep remains additive over the first 6 mo of life. Our
      results also show that the loop gain of the respiratory control system is reduced
      with age, possibly as a result of a reduction of peripheral O(2) sensitivity.

PMID- 19745192
TI  - Pulmonary perfusion heterogeneity is increased by sustained, heavy exercise in
      humans.
AB  - Exercise presents a considerable stress to the pulmonary system and ventilation
      perfusion (Va/Q) heterogeneity increases with exercise, affecting the efficiency
      of gas exchange. In particular, prolonged heavy exercise and maximal exercise are
      known to increase Va/Q heterogeneity and these changes persist into recovery. We
      hypothesized that the spatial heterogeneity of pulmonary perfusion would be
      similarly elevated after prolonged exercise. To test this, athletic subjects (n =
      6, Vo(2max) = 61 ml. kg(-1).min(-1)) with exercising Va/Q heterogeneity
      previously characterized by the multiple inert gas elimination technique (MIGET),
      performed 45 min of cycle exercise at approximately 70% Vo(2max). MRI arterial
      spin labeling measures of pulmonary perfusion were acquired pre- and postexercise
      (at 20, 40, 60 min post) to quantify the spatial distribution in isogravitational
      (coronal) and gravitationally dependent (sagittal) planes. Regional proton
      density measurements allowed perfusion to be normalized for density and
      quantified in milliliters per minute per gram. Mean lung density did not change
      significantly in either plane after exercise (P = 0.19). Density-normalized
      perfusion increased in the sagittal plane postexercise (P =or <0.01) but
      heterogeneity did not (all P >or= 0.18), likely because of perfusion
      redistribution and vascular recruitment. Density-normalized perfusion was
      unchanged in the coronal plane postexercise (P = 0.66), however, perfusion
      heterogeneity was significantly increased as measured by the relative dispersion
      [RD, pre 0.62(0.07), post 0.82(0.21), P < 0.0001] and geometric standard
      deviation [GSD, pre 1.74(0.14), post 2.30(0.56), P < 0.005]. These changes in
      heterogeneity were related to the exercise-induced changes of the log standard
      deviation of the ventilation distribution, an MIGET index of Va/Q heterogeneity
      (RD R(2) = 0.68, P < 0.05, GSD, R(2) = 0.55, P = 0.09). These data are consistent
      with but not proof of interstitial pulmonary edema as the mechanism underlying
      exercise-induced increases in both spatial perfusion heterogeneity and Va/Q
      heterogeneity.

PMID- 19745193
TI  - Pulmonary responses to subacute ozone exposure in obese vs. lean mice.
AB  - The purpose of this study was to determine whether obesity affects pulmonary
      responses following a 3-day ozone exposure. Obese db/db and lean wild-type mice
      were exposed to ozone (0.3 ppm) for 72 h. In wild-type mice, ozone exposure
      caused pulmonary injury and inflammation, and these events were associated with
      reduced pulmonary compliance. In db/db mice, ozone-induced neutrophil recruitment
      to the lung was reduced and no reduction in compliance was observed. Similar
      results were obtained in obese Cpe(fat) mice, indicating that loss of leptin
      signaling in db/db mice does not account for these obesity-related changes. To
      examine the role of interleukin (IL)-6 in this obesity-related difference in
      ozone responsiveness, wild-type and IL-6-deficient mice were raised on 10% or 60%
      fat diets. Compared with 10% fat-fed mice, wild-type 60% fat-fed mice were obese
      and had reduced neutrophil recruitment following ozone. IL-6 deficiency reduced
      ozone-induced neutrophil recruitment in 10% fat-fed mice. In contrast, in obese
      mice, no effect of IL-6 deficiency on neutrophil recruitment was observed.
      Obesity-related differences in the effect of ozone on compliance were observed in
      both wild-type and IL-6-deficient mice. Obesity-related differences in serum IL-6
      were observed and may account for obesity-related differences in the effect of IL
      6 deficiency on neutrophil recruitment. In summary, the neutrophilic inflammation
      induced by prolonged low level ozone exposure was attenuated in obese mice and
      appeared to result from an absence of IL-6-dependent neutrophil recruitment in
      the obese mice.

PMID- 19745194
TI  - Protective mechanical ventilation does not exacerbate lung function impairment or
      lung inflammation following influenza A infection.
AB  - The degree to which mechanical ventilation induces ventilator-associated lung
      injury is dependent on the initial acute lung injury (ALI). Viral-induced ALI is
      poorly studied, and this study aimed to determine whether ALI induced by a
      clinically relevant infection is exacerbated by protective mechanical
      ventilation. Adult female BALB/c mice were inoculated with 10(4.5) plaque-forming
      units of influenza A/Mem/1/71 in 50 microl of medium or medium alone. This study
      used a protective ventilation strategy, whereby mice were anesthetized,
      tracheostomized, and mechanically ventilated for 2 h. Lung mechanics were
      measured periodically throughout the ventilation period using a modification of
      the forced oscillation technique to obtain measures of airway resistance and
      coefficients of tissue damping and tissue elastance. Thoracic gas volume was
      measured and used to obtain specific airway resistance, tissue damping, and
      tissue elastance. At the end of the ventilation period, a bronchoalveolar lavage
      sample was collected to measure inflammatory cells, macrophage inflammatory
      protein-2, IL-6, TNF-alpha, and protein leak. Influenza infection caused
      significant increases in inflammatory cells, protein leak, and deterioration in
      lung mechanics that were not exacerbated by mechanical ventilation, in contrast
      to previous studies using bacterial and mouse-specific viral infection. This
      study highlighted the importance of type and severity of lung injury in
      determining outcome following mechanical ventilation.

PMID- 19745195
TI  - Synergistic and antagonistic interactions in the rat forelimb: acute effects of
      coactivation.
AB  - The goals of the present study were 1) to assess effects of antagonist
      coactivation on mechanical interactions between synergistic muscles, and 2) to
      quantify the extent of epimuscular myofascial force transmission between
      synergistic and antagonistic muscles in the rat forelimb. Connective tissues
      enveloping the muscle bellies in the antebrachium were left intact. Forces
      exerted at the distal tendons of flexor carpi ulnaris (FCU), palmaris longus
      (PL), and extensor carpi ulnaris (ECU) muscles were measured at various FCU
      lengths for two different stimulation protocols: 1) simultaneous stimulation of
      ulnar/median nerve complex (exciting all wrist flexors, including synergistic FCU
      and PL) and radial nerve (exciting all wrist extensors, including antagonistic
      ECU); and 2) stimulation of the ulnar/median nerve exclusively. PL and ECU were
      kept at a constant length. In addition, muscle forces were measured during
      stimulation of one of the indicated nerves, with later addition of stimulation of
      the second nerve during the maintained tetanic contraction. Coactivation of
      antagonistic muscles increased FCU isometric forces (on average, by 10% of
      optimal force) and PL forces (on average, by 13% of maximal force), but
      mechanical interaction between FCU and PL was unchanged. Changing the length and
      relative position of FCU significantly affected PL (by 20%) as well as ECU forces
      (by 8%). In addition, distal tetanic force of FCU kept at a constant high length
      was determined by the order of nerve stimulation onset. These results indicate
      effects of myofascial pathways between synergistic and antagonistic muscles in
      the rat forelimb. Coactivation may enhance the stiffness of connective tissues
      between muscles, but the present data suggest that activation of all wrist
      flexors already preloaded the myofascial pathways to the greatest extent. The
      stimulation order effects were explained by dynamic features of muscle and
      connective tissues (i.e., length-history dependence and viscoelasticity).

PMID- 19745196
TI  - The role of working memory and fluency practice on the reading comprehension of
      students who are dysfluent readers.
AB  - The authors investigated whether practice in reading fluency had a causal
      influence on the relationship between working memory (WM) and text comprehension
      for 155 students in Grades 2 and 4 who were poor or average readers. Dysfluent
      readers were randomly assigned to repeated reading or continuous reading practice
      conditions and compared with untreated dysfluent and fluent readers on posttest
      measures of fluency, word identification, vocabulary, and reading comprehension.
      Three main findings emerged: (a) The influence of WM on text comprehension was
      not related to fluency training, (b) dysfluent readers in the continuous-reading
      condition had higher posttest scores than dysfluent readers in the other
      conditions on measures of text comprehension but not on vocabulary, and (c)
      individual differences in WM better predicted posttest comprehension performance
      than word-attack skills. In general, the results suggested that although
      continuous reading increased comprehension, fluency practice did not compensate
      for WM demands. The results were interpreted within a model that viewed reading
      comprehension processes as competing for a limited supply of WM resources that
      operate independent of fluency.

PMID- 19745197
TI  - Tumor necrosis factor-alpha potentiates RhoA-mediated monocyte transmigratory
      activity in vivo at a picomolar level.
AB  - OBJECTIVE: The serum level of tumor necrosis factor-alpha (TNF-alpha) is in the
      picomolar range under inflammatory conditions. We investigated whether these
      picomolar levels of TNF-alpha directly modulate the functional activities of
      circulating monocytes. METHODS AND RESULTS: In THP-1 monocytes treated with TNF
      alpha (1 to 100 pmol/L/30 minutes), cytosolic RhoA small GTPase rapidly
      translocated to the plasma membrane via functionally active ezrin/radixin/moesin
      (ERM) complex, a cytoskeletal linker, and subsequent actin polymerization through
      NF-kappaB activation. The threonine phosphorylation of ERM was accomplished by
      the activation of TNF receptor type I (TNFRI) and signaling pathways involving
      PI3K and an atypical PKC; ie, PKCzeta. The TNF-alpha-treated monocytes (10
      pmol/L) displayed more potent and prolonged generation of GTP-bound RhoA in
      response to secondary stimulation with RhoA-activating monocyte chemoattractant
      protein-1 (MCP-1). Clearly, human circulating monocytes preconditioned by 10
      pmol/L TNF-alpha augmented MCP-1-mediated chemotaxis and firm adhesion on VCAM-1
      and ICAM-1 in vitro and ex vivo. The elevation of serum TNF-alpha (>5 pmol/L
      within 16 hours), which was introduced by intraperitoneal injection of mouse
      specific TNF-alpha to C57/BL6 mice, enhanced the number of CD80+ monocytes
      transmigrating to the JE/MCP-1-injected intraperitoneal space. CONCLUSIONS:
      Picomolar concentrations of TNF-alpha in the bloodstream may prime the RhoA
      dependent activities of circulating monocytes to enhance recruitment to active
      inflammatory foci.

PMID- 19745198
TI  - Ablation of angiotensin IV receptor attenuates hypofibrinolysis via PAI-1
      downregulation and reduces occlusive arterial thrombosis.
AB  - OBJECTIVE: Reduced fibrinolytic activity is associated with adverse
      cardiovascular events. Although insulin-regulated aminopeptidase (IRAP) was
      recently identified as the angiotensin (Ang) IV receptor (AT4R), the impact of
      AngIV-AT4R signaling distal to AngII on the activation of type-1 plasminogen
      activator inhibitor (PAI-1) in the fibrinolytic process and subsequent formation
      of thrombosis remains unclarified. METHODS AND RESULTS: To determine whether
      AngIV would inhibit fibrinolysis via PAI-1 activation and promote thrombosis, we
      evaluated the degree of fibrinolysis in thrombosis models and investigated the
      roles of AT4R after vascular injury using IRAP knockout mice (IRAP(-/-)). In
      endothelial cells from control mice (WT; C57Bl6/J), both AngII and AngIV
      treatments increased PAI-1 mRNA expression in a dose-dependent manner, whereas
      the response was blunted in endothelial cells from IRAP(-/-) mice. FeCl(3)
      induced thrombosis was suppressed in the carotid arteries of IRAP(-/-) mice when
      compared with WT mice. Similarly, in a model of carotid artery ligation and cuff
      placement, IRAP(-/-) mice demonstrated accelerated fibrinolysis 7 days after
      surgery and reduced occlusive thrombosis with negative remodeling at 28 days.
      CONCLUSIONS: AngIV-AT4R signaling has a key role in fibrinolysis and the
      subsequent formation of arterial thrombosis after vascular injury. AT4R may be a
      novel therapeutic target against cardiovascular disease.

PMID- 19745199
TI  - Mapping 3-dimensional neovessel organization steps using micro-computed
      tomography in a murine model of hindlimb ischemia-brief report.
AB  - OBJECTIVE: Studying the mechanisms of neovascularization and evaluating the
      effects of proangiogenic strategies require accurate analysis of the neovascular
      network. We sought to evaluate the contribution of the microcomputed tomography
      (mCT) providing high-resolution 3-dimensional (3D) structural data, to a better
      comprehension of the well-studied mouse hindlimb postischemic neovascularization.
      METHODS AND RESULTS: We showed a predominant arteriogenesis process in the thigh
      and a predominant angiogenesis-related process in the tibiofibular region, in
      response to ischemia during the first 15 days. After 15 days, mCT quantitative
      analysis reveals a remodeling of arterial neovessels and a regression depending
      on the restoration of the blood flow. We provided also new mCT data on the rapid
      and potent angiogenic effects of mesenchymal stem cell therapy on vessel
      formation and organization. We discussed the contribution of this technique
      compared with or in addition to data generated by the more conventional
      approaches. CONCLUSIONS: This study demonstrated that optimized mCT is a robust
      method for providing new insights into the 3D understanding of postischemic
      vessel formation.

PMID- 19745200
TI  - Emotions as within or between people? Cultural variation in lay theories of
      emotion expression and inference.
AB  - Four studies using open-ended and experimental methods test the hypothesis that
      in Japanese contexts, emotions are understood as between people, whereas in
      American contexts, emotions are understood as primarily within people. Study 1
      analyzed television interviews of Olympic athletes. When asked about their
      relationships, Japanese athletes used significantly more emotion words than
      American athletes. This difference was not significant when questions asked
      directly about athletes' feelings. In Study 2, when describing an athlete's
      emotional reaction to winning, Japanese participants implicated others more often
      than American participants. After reading an athlete's self-description, Japanese
      participants inferred more emotions when the athlete mentioned relationships,
      whereas American participants inferred more emotions when the athlete focused
      only on herself (Study 3). Finally, when viewing images of athletes, Japanese
      participants inferred more emotions for athletes pictured with teammates, whereas
      American participants inferred more emotions for athletes pictured alone (Studies
      4a and 4b).

PMID- 19745201
TI  - A functional polymorphism in IL-18 is associated with severity of bronchial
      asthma.
AB  - RATIONALE: IL-18 is a unique cytokine that enhances innate immunity and both Th1-
      and Th2-driven immune responses. Recent murine and human genetic studies have
      shown its role in the pathogenesis of asthma. OBJECTIVES: We conducted an
      association study in a Japanese population to discover variants of IL-18 that
      might have an effect on asthma susceptibility and/or progression and conducted
      functional analyses of the related variants. METHODS: The IL-18 gene locus was
      resequenced in 48 human chromosomes. Asthma severity was determined according to
      the 2002 Global Initiative for Asthma Guidelines. Association and haplotype
      analyses were performed using 1,172 subjects. MEASUREMENTS AND MAIN RESULTS:
      Although no polymorphisms differed significantly in frequency between the control
      and adult asthma groups, rs5744247 C>G was significantly associated with the
      severity of adult asthma (steps 1, 2 vs. steps 3, 4; P = 0.0034). We also found a
      positive association with a haplotype (P = 0.0026). By in vitro functional
      analyses, the rs5744247 variant was found to increase enhancer-reporter activity
      of the IL-18 gene in bronchial epithelial cells. Expression levels of IL-18 in
      response to LPS stimulation in monocytes were significantly greater in subjects
      homozygous for the susceptibility G allele at rs5744247 C>G. Furthermore, we
      found a significant correlation between the serum IL-18 level and the genotype of
      rs5744247 (P = 0.031). CONCLUSIONS: Although the association results need to be
      replicated by other studies, IL-18 variants are significantly associated with
      asthma severity, and the rs5744247 variant reflects higher transcriptional
      activity and higher expression of IL-18 in LPS-stimulated monocytes and a higher
      serum IL-18 level.

PMID- 19745202
TI  - Days of delirium are associated with 1-year mortality in an older intensive care
      unit population.
AB  - RATIONALE: Delirium is a frequent occurrence in older intensive care unit (ICU)
      patients, but the importance of the duration of delirium in contributing to
      adverse long-term outcomes is unclear. OBJECTIVES: To examine the association of
      the number of days of ICU delirium with mortality in an older patient population.
      METHODS: We performed a prospective cohort study in a 14-bed ICU in an urban
      acute care hospital. The patient population comprised 304 consecutive admissions
      60 years of age and older. MEASUREMENTS AND MAIN RESULTS: The main outcome was 1
      year mortality after ICU admission. Patients were assessed daily for delirium
      with the Confusion Assessment Method for the ICU and a validated chart review
      method. The median duration of ICU delirium was 3 days (range, 1-46 d). During
      the follow-up period, 153 (50%) patients died. After adjusting for relevant
      covariates, including age, severity of illness, comorbid conditions, psychoactive
      medication use, and baseline cognitive and functional status, the number of days
      of ICU delirium was significantly associated with time to death within 1 year
      post-ICU admission (hazard ratio, 1.10; 95% confidence interval, 1.02-1.18).
      CONCLUSIONS: Number of days of ICU delirium was associated with higher 1-year
      mortality after adjustment for relevant covariates in an older ICU population.
      Investigations should be undertaken to reduce the number of days of ICU delirium
      and to study the impact of this reduction on important health outcomes, including
      mortality and functional and cognitive status.

PMID- 19745203
TI  - Impaired vascular regulation in patients with obstructive sleep apnea: effects of
      continuous positive airway pressure treatment.
AB  - RATIONALE: Impaired endothelium-dependent vasodilation has been documented in
      patients with sleep apnea. This impairment may result in blood flow dysregulation
      during apnea-induced fluctuations in arterial blood gases. OBJECTIVES: To test
      the hypothesis that hypoxic and hypercapnic vasodilation in the forearm and
      cerebral circulation are impaired in patients with sleep apnea. METHODS: We
      exposed 20 patients with moderate to severe sleep apnea and 20 control subjects,
      to isocapnic hypoxia and hyperoxic hypercapnia. A subset of 14 patients was
      restudied after treatment with continuous positive airway pressure. MEASUREMENTS
      AND MAIN RESULTS: Cerebral flow velocity (transcranial Doppler), forearm blood
      flow (venous occlusion plethysmography), arterial pressure (automated
      sphygmomanometry), oxygen saturation (pulse oximetry), ventilation
      (pneumotachograph), and end-tidal oxygen and carbon dioxide tensions (expired gas
      analysis) were measured during three levels of hypoxia and two levels of
      hypercapnia. Cerebral vasodilator responses to hypoxia (-0.65 +/- 0.44 vs. -1.02
      +/- 0.72 [mean +/- SD] units/% saturation; P = 0.03) and hypercapnia (2.01 +/-
      0.88 vs. 2.57 +/- 0.89 units/mm Hg; P = 0.03) were smaller in patients versus
      control subjects. Hypoxic vasodilation in the forearm was also attenuated (-0.05
      +/- 0.09 vs. -0.10 +/- 0.09 unit/% saturation; P = 0.04). Hypercapnia did not
      elicit forearm vasodilation in either group. Twelve weeks of continuous positive
      airway pressure treatment enhanced hypoxic vasodilation in the cerebral
      circulation (-0.83 +/- 0.32 vs. -0.46 +/- 0.29 units/% saturation; P = 0.01) and
      forearm (-0.19 +/- 0.15 vs. -0.02 +/- 0.08 units/% saturation; P = 0.003), and
      hypercapnic vasodilation in the brain showed a trend toward improvement (2.24 +/-
      0.78 vs. 1.76 +/- 0.64 units/mm Hg; P = 0.06). CONCLUSIONS: Vasodilator responses
      to chemical stimuli in the cerebral circulation and the forearm are impaired in
      many patients with obstructive sleep apnea. Some of these impairments can be
      improved with continuous positive airway pressure.

PMID- 19745204
TI  - Lung volume reference values for women and men 65 to 85 years of age.
AB  - RATIONALE: In elderly subjects, static lung volumes are interpreted using
      prediction equations derived from primarily younger adult populations.
      OBJECTIVES: To provide reference equations for static lung volumes for European
      adults 65 to 85 years of age and to compare the predicted values of this sample
      with those from other studies including middle-aged adults. We compare the lung
      volumes by plethysmography and helium dilution in elderly subjects. METHODS:
      Reference equations were derived from a randomly selected sample from the general
      population of 321 healthy never-smoker subjects 65 to 85 years of age. Spirometry
      and lung volume determinations by plethysmography and multibreath helium
      equilibration method were performed following the American Thoracic
      Society/European Respiratory Society recommendations. Reference values and lower
      and upper limits of normal were derived using a piecewise polynomial model.
      MEASUREMENTS AND MAIN RESULTS: Plethysmography provided higher values than the
      dilutional method for all lung volumes, with wide limits of agreement. In
      addition to height, our reference equations confirm the age- and body size
      dependence of lung volumes in older subjects. Practically all the estimations
      performed by extrapolating reference equations of middle-aged adults
      overpredicted the true lung volumes of our healthy elderly volunteers. Middle
      aged reference equations classify subjects as being below the total lung capacity
      lower limit of normal between 17.9 and 62.5% of the women and between 12.5 and
      42.2% of the men of the current study. CONCLUSIONS: These results underscore the
      importance of using prediction equations appropriate to the origin, age, and
      height characteristics of the subjects being studied.

PMID- 19745205
TI  - Ambient metals, elemental carbon, and wheeze and cough in New York City children
      through 24 months of age.
AB  - RATIONALE: The effects of exposure to specific components of ambient fine
      particulate matter (PM(2.5)), including metals and elemental carbon (EC), have
      not been fully characterized in young children. OBJECTIVES: To compare temporal
      associations among PM(2.5); individual metal constituents of ambient PM(2.5),
      including nickel (Ni), vanadium (V), and zinc (Zn); and EC and longitudinal
      reports of respiratory symptoms through 24 months of age. METHODS: Study
      participants were selected from the Columbia Center for Children's Environmental
      Health birth cohort recruited in New York City between 1998 and 2006. Respiratory
      symptom data were collected by questionnaire every 3 months through 24 months of
      age. Ambient pollutant data were obtained from state-operated stationary
      monitoring sites located within the study area. For each subject, 3-month average
      inverse-distance weighted concentrations of Ni, V, Zn, EC, and PM(2.5) were
      calculated for each symptom-reporting period based on the questionnaire date and
      the preceding 3 months. Associations between pollutants and symptoms were
      characterized using generalized additive mixed effects models, adjusting for sex,
      ethnicity, environmental tobacco smoke exposure, and calendar time. MEASUREMENTS
      AND MAIN RESULTS: Increases in ambient Ni and V concentrations were associated
      significantly with increased probability of wheeze. Increases in EC were
      associated significantly with cough during the cold/flu season. Total PM(2.5) was
      not associated with wheeze or cough. CONCLUSIONS: These results suggest that
      exposure to ambient metals and EC from heating oil and/or traffic at levels
      characteristic of urban environments may be associated with respiratory symptoms
      among very young children.

PMID- 19745206
TI  - Exposure to traffic-related particles and endotoxin during infancy is associated
      with wheezing at age 3 years.
AB  - RATIONALE: Murine models demonstrate a synergistic production of reactive oxygen
      species on coexposure to diesel exhaust particles and endotoxin. OBJECTIVES: It
      was hypothesized that coexposure to traffic-related particles and endotoxin would
      have an additive effect on persistent wheezing during early childhood. METHODS:
      Persistent wheezing at age 36 months was assessed in the Cincinnati Childhood
      Allergy and Air Pollution Study, a high-risk birth cohort. A time-weighted
      average exposure to traffic-related particles was determined by applying a land
      use regression model to the homes, day cares, and other locations where children
      spent time from birth through age 36 months. Indoor levels of endotoxin were
      measured from dust samples collected before age 12 months. The relationship
      between dichotomized (<or>or=75th percentile) traffic-related particle and
      endotoxin exposure and persistent wheezing, controlling for potential covariates,
      was examined. MEASUREMENTS AND MAIN RESULTS: Persistent wheezing at age 36 months
      was significantly associated with exposure to increased levels of traffic-related
      particles before age 12 months (OR = 1.75; 95% confidence interval, 1.07-2.87).
      Coexposure to endotoxin had a synergistic effect with traffic exposure on
      persistent wheeze (OR = 5.85; 95% confidence interval, 1.89-18.13) after
      adjustment for significant covariates. CONCLUSIONS: The association between
      traffic-related particle exposure and persistent wheezing at age 36 months is
      modified by exposure to endotoxin. This finding supports prior toxicological
      studies demonstrating a synergistic production of reactive oxygen species after
      coexposure to diesel exhaust particles and endotoxin. The effect of early versus
      later exposure to traffic-related particles, however, remains to be studied
      because of the high correlation between exposure throughout the first 3 years of
      life.

PMID- 19745207
TI  - HIV infection does not affect active case finding of tuberculosis in South
      African gold miners.
AB  - RATIONALE: Gold miners in South Africa undergo annual radiological screening for
      tuberculosis in an occupational health center of a gold mining company, but the
      optimal screening algorithm is unclear. OBJECTIVES: To evaluate methods for
      active case detection of tuberculosis. METHODS: A sequential sample of miners
      attending annual medical examination was screened for tuberculosis using a
      symptom questionnaire, chest radiograph, and two sputum specimens for microscopy
      and culture. MEASUREMENTS AND MAIN RESULTS: There were 1,955 miners included in
      this study; all were male with a median age of 41 years (range, 20-61 yr).
      Presence of at least one of a trio of symptoms (new or worsening cough, night
      sweats, or weight loss) had similar sensitivity (29.4%) to either chest
      radiograph (25.5%) or sputum smear (25.5%). These sensitivities did not differ by
      HIV status. Presence of one or more elements of the symptom trio and/or new
      radiological abnormality substantially increased sensitivity to 49.0%.
      Specificity of the symptom trio was higher in HIV-uninfected (91.8%) than in HIV
      infected persons (88.2%; P = 0.018). Specificity of chest radiography and smear
      were similar (98.7% and 99.0%, respectively) and did not differ by HIV status
      (both P values > 0.8). CONCLUSIONS: In a population of gold miners who undergo
      regular radiological screening, the addition of chest radiography to symptom
      screening substantially improved the sensitivity and positive predictive value.
      HIV infection did not alter the sensitivity of the screening tool.

PMID- 19745209
TI  - Research in pediatric palliative care: closing the gap between what is and is not
      known.
AB  - Pediatric palliative care provides physical and psychosocial care to children
      with life-limiting illnesses and their families. Services are provided by
      physicians, nurses, volunteers, and other providers in a myriad of settings. Over
      the past 30 years, a portfolio of research has amassed on palliative care. Yet,
      much remains unknown, particularly about pediatric palliative care. This article
      is the first in a series and it provides a general overview of what is known and
      unknown about the provision and need for pediatric palliative care. Subsequent
      articles will focus on specific topics such as decision making and support care.
      The purpose of this series is to inform and promote discussion about research in
      pediatric palliative care.

PMID- 19745208
TI  - Sex differences in acoustic startle responses and seizure thresholds between
      ethanol-withdrawn male and female rats.
AB  - AIMS: We have found consistent and significant sex differences in recovery from
      the increased seizure susceptibility observed during ethanol withdrawal (EW) in
      our rat model system. The main objective of the present study was to determine if
      sex differences in EW generalized to an additional behavioral measure startle
      reactivity. METHODS: Acoustic startle or seizure threshold responses were
      measured in separate groups of rats at 1 day or 3 days of EW. RESULTS: Both pair
      fed control and EW males showed greater increases in acoustic startle responses
      than either the female or ovariectomized female (OVX) counterparts. There was a
      selective effect of pregnanolone on acoustic startle in that it reduced peak
      force of response only at 3 days EW in male rats. Unexpectedly, it modestly
      increased startle reactivity in control female and OVX rats. Acute treatment with
      low-dose ethanol trended toward reducing startle responses in control animals, as
      expected, while generally enhancing startle responses during EW. All sex
      conditions showed an enhanced startle response during EW following administration
      of the higher dose of estradiol compared to control animals. Estradiol did not
      alter seizure thresholds in control animals. However, it was anticonvulsant for
      males at 3 days EW, females and OVX at 1 day EW. CONCLUSIONS: Observed sex
      differences in the startle reactivity during EW were consistent with earlier
      findings comparing EW seizure risk in male and female rats. Responses of OVX
      suggested that both hormones and differences in brain structures between males
      and females have a role in these sex differences. Our findings add weight to
      recommendations that treatment of alcohol withdrawal in humans should consider
      hormonal status as well as withdrawal time.

PMID- 19745210
TI  - Methylphenidate side effects in advanced cancer: a retrospective analysis.
AB  - INTRODUCTION: Methylphenidate (MP) is often recommended for symptom control in
      advanced cancer. Little is known about its side effects in frail adults.
      OBJECTIVES: To evaluate MP-associated symptoms or side effects (S/E). METHODS:
      Data was collected from 2 published prospective cohort series and a phase 2 study
      of MP for symptom control in advanced cancer. All 3 reports had identical dosing
      schedules and symptom assessments. Initial MP doses were 10 mg/d (5 mg at 8 AM
      and at 12 noon) titrated up to a maximum of 30 mg/d. Depression, fatigue, and
      symptoms identified as possible MP S/E were evaluated for presence (prevalence)
      and for severity (using categorical scales) before MP (day 0) and on days 3, 5,
      and 7 thereafter. The categorical scale used was none, mild, moderate, and
      severe. RESULTS: 62 patients were enrolled. Fifty completed 7 days of MP with a
      median age of 69 (range 30-90) years. Thirty-five received MP 10 mg/day. Most
      (96%) had improvement in depression and/or fatigue. Among the 62 patients, new
      symptom prevalence throughout the study was agitation (16%), insomnia (16%), dry
      mouth (15%), nausea (10%), tremors (6%), anorexia (5%), headache (3%),
      palpitations (2%), and vomiting (2%). Patients could have more than 1 symptom
      simultaneously. Seven (11%) withdrew due to MP S/E. Some symptoms present before
      MP showed significant improvement during MP therapy. CONCLUSIONS: (1) Treatment
      with MP (10-20 mg/d) in advanced cancer is well tolerated. (2) S/E symptoms with
      MP appeared to improve spontaneously despite continued MP therapy. (3) Depression
      and fatigue improved at doses lower than those recommended in other clinical
      conditions. (4) MP improved depression and fatigue, and some secondary symptoms
      associated with them. Methylphenidate (MP) appears safe when used in the
      treatment of depression and fatigue in advanced cancer.

PMID- 19745211
TI  - The Padua Inventory: do revisions need revision?
AB  - The purpose of the present study was to examine the psychometric properties,
      factorial structure, and validity of the Padua Inventory-Washington State
      University Revision and of the Padua Inventory-Revised in a large sample of
      patients with obsessive-compulsive disorder (n = 228) and with anxiety disorders
      and/or depression (n = 213). The five-factor structures of both revisions were
      not replicated. A 24-item revision, referred to as the Padua Inventory-Palatine
      Revision (PI-PR), was developed on the basis of both theoretical and statistical
      considerations. The PI-PR assesses six subscales: Contamination and Washing,
      Checking, Numbers, Dressing and Grooming, Rumination, and Harming Obsessions and
      Impulses. The results demonstrate that the PI-PR is a brief, psychometrically
      sound, and valid measure for the assessment of a broad range of obsessive
      compulsive symptoms, which has important advantages over both previous revisions.

PMID- 19745212
TI  - Traveling with cognitive tests: testing the validity of a KABC-II adaptation in
      India.
AB  - The authors evaluated the adequacy of an extensive adaptation of the American
      Kaufman Assessment Battery for Children, second edition (KABC-II), for 6- to 10
      year-old Kannada-speaking children of low socioeconomic status in Bangalore,
      South India. The adapted KABC-II was administered to 598 children. Subtests
      showed high reliabilities, the Cattell-Horn-Carroll model underlying the original
      KABC-II was largely replicated, and external relations with demographic
      characteristics and an achievement measure were consistent with expectations. The
      subtests showed relatively high loadings on the general cognitive factor,
      presumably because of the high task novelty and, hence, cognitive complexity of
      the tests for the children. The findings support the suitability and validity of
      the KABC-II adaptation. The authors emphasize that test adaptations can only be
      adequate if they meet both judgmental (qualitative) and statistical
      (quantitative) adaptation criteria.

PMID- 19745213
TI  - Pandemic influenza vaccine policy--considering the early evidence.

PMID- 19745214
TI  - Cross-reactive antibody responses to the 2009 pandemic H1N1 influenza virus.
AB  - BACKGROUND: A new pandemic influenza A (H1N1) virus has emerged, causing illness
      globally, primarily in younger age groups. To assess the level of preexisting
      immunity in humans and to evaluate seasonal vaccine strategies, we measured the
      antibody response to the pandemic virus resulting from previous influenza
      infection or vaccination in different age groups. METHODS: Using a
      microneutralization assay, we measured cross-reactive antibodies to pandemic H1N1
      virus (2009 H1N1) in stored serum samples from persons who either donated blood
      or were vaccinated with recent seasonal or 1976 swine influenza vaccines.
      RESULTS: A total of 4 of 107 persons (4%) who were born after 1980 had
      preexisting cross-reactive antibody titers of 40 or more against 2009 H1N1,
      whereas 39 of 115 persons (34%) born before 1950 had titers of 80 or more.
      Vaccination with seasonal trivalent inactivated influenza vaccines resulted in an
      increase in the level of cross-reactive antibody to 2009 H1N1 by a factor of four
      or more in none of 55 children between the ages of 6 months and 9 years, in 12 to
      22% of 231 adults between the ages of 18 and 64 years, and in 5% or less of 113
      adults 60 years of age or older. Seasonal vaccines that were formulated with
      adjuvant did not further enhance cross-reactive antibody responses. Vaccination
      with the A/New Jersey/1976 swine influenza vaccine substantially boosted cross
      reactive antibodies to 2009 H1N1 in adults. CONCLUSIONS: Vaccination with recent
      seasonal nonadjuvanted or adjuvanted influenza vaccines induced little or no
      cross-reactive antibody response to 2009 H1N1 in any age group. Persons under the
      age of 30 years had little evidence of cross-reactive antibodies to the pandemic
      virus. However, a proportion of older adults had preexisting cross-reactive
      antibodies.

PMID- 19745215
TI  - Trial of 2009 influenza A (H1N1) monovalent MF59-adjuvanted vaccine.
AB  - BACKGROUND: The 2009 pandemic influenza A (H1N1) virus has emerged to cause the
      first pandemic of the 21st century. Development of effective vaccines is a public
      health priority. METHODS: We conducted a single-center study, involving 176
      adults, 18 to 50 years of age, to test the monovalent influenza A/California/2009
      (H1N1) surface-antigen vaccine, in both MF59-adjuvanted and nonadjuvanted forms.
      Subjects were randomly assigned to receive two intramuscular injections of
      vaccine containing 7.5 microg of hemagglutinin on day 0 in each arm or one
      injection on day 0 and the other on day 7, 14, or 21; or two 3.75-microg doses of
      MF59-adjuvanted vaccine, or 7.5 or 15 microg of nonadjuvanted vaccine,
      administered 21 days apart. Antibody responses were measured by means of
      hemagglutination-inhibition assay and a microneutralization assay on days 0, 14,
      21, and 42 after injection of the first dose. RESULTS: The most frequent local
      and systemic reactions were pain at the injection site and muscle aches, noted in
      70% and 42% of subjects, respectively; reactions were more common with the MF59
      adjuvanted vaccine than with nonadjuvanted vaccine. Three subjects reported
      fever, with a temperature of 38 degrees C or higher, after either dose. Antibody
      titers, expressed as geometric means, were higher at day 21 among subjects who
      had received one dose of MF59-adjuvanted vaccine than among those who had
      received one dose of nonadjuvanted vaccine (P<0.001 by the microneutralization
      assay). By day 21, hemagglutination-inhibition and microneutralization antibody
      titers of 1:40 or more were seen in 77 to 96% and 92 to 100% of subjects
      receiving MF59-adjuvanted vaccine, respectively, and in 63 to 72% and 67 to 76%
      of those receiving nonadjuvanted vaccine, respectively. By day 42, after two
      doses of vaccine, hemagglutination-inhibition and microneutralization antibody
      titers of 1:40 or more were seen in 92 to 100% and 100% of recipients of MF59
      adjuvanted vaccine, respectively, and in 74 to 79% and 78 to 83% of recipients of
      nonadjuvanted vaccine, respectively. CONCLUSIONS: Monovalent 2009 influenza A
      (H1N1) MF59-adjuvanted vaccine generates antibody responses likely to be
      associated with protection after a single dose is administered.
      (ClinicalTrials.gov number, NCT00943358).

PMID- 19745216
TI  - Response to a monovalent 2009 influenza A (H1N1) vaccine.
AB  - BACKGROUND: A novel 2009 influenza A (H1N1) virus is responsible for the first
      influenza pandemic in 41 years. A safe and effective vaccine is needed. A
      randomized, observer-blind, parallel-group trial evaluating two doses of an
      inactivated, split-virus 2009 H1N1 vaccine in healthy adults between the ages of
      18 and 64 years is ongoing at a single site in Australia. METHODS: We evaluated
      the immunogenicity and safety of the vaccine after each of two scheduled doses,
      administered 21 days apart. A total of 240 subjects, equally divided into two age
      groups (<50 years and >or=50 years), were enrolled and underwent randomization to
      receive either 15 microg or 30 microg of hemagglutinin antigen by intramuscular
      injection. We measured antibody titers using hemagglutination-inhibition and
      microneutralization assays at baseline and 21 days after vaccination. The
      coprimary immunogenicity end points were the proportion of subjects with antibody
      titers of 1:40 or more on hemagglutination-inhibition assay, the proportion of
      subjects with either seroconversion or a significant increase in antibody titer,
      and the factor increase in the geometric mean titer. RESULTS: By day 21 after the
      first dose, antibody titers of 1:40 or more were observed in 114 of 120 subjects
      (95.0%) who received the 15-microg dose and in 106 of 119 subjects (89.1%) who
      received the 30-microg dose. A similar result was observed after the second dose
      of vaccine. No deaths, serious adverse events, or adverse events of special
      interest were reported. Local discomfort (e.g., injection-site tenderness or
      pain) was reported by 56.3% of subjects, and systemic symptoms (e.g., headache)
      by 53.8% of subjects after each dose. Nearly all events were mild to moderate in
      intensity. CONCLUSIONS: A single 15-microg dose of 2009 H1N1 vaccine was
      immunogenic in adults, with mild-to-moderate vaccine-associated reactions.
      (ClinicalTrials.gov number, NCT00938639).

PMID- 19745217
TI  - Salvaging penile venous stripping surgery.
AB  - Disappointing functional outcome and penile deformity are major concerns of
      penile venous surgery. Consequently, it has been abandoned by most urologists. To
      explore whether penile deformity is correctable and erectile function can be
      improved, we report our experience in patients who had undergone surgery
      elsewhere. From 1986 to 2008, 16 consecutive patients sought our assistance
      because of poorer erectile capability or/and penile deformity from previous
      venous surgery elsewhere. The abridged 5-item version of the International Index
      of Erectile Function (IIEF-5) was used to score the patients when it became
      available in 1998. Accordingly, 3 and 13 patients were categorized into the non
      IIEF and IIEF groups, respectively. A median longitudinal pubic incision and a
      circumferential or semicircumcision were made to relieve the fibrotic tissues for
      accessing the deep dorsal veins, which were stripped thoroughly and ligated with
      6-0 nylon sutures. The cavernosal veins were managed in a similar manner. The
      paraarterial veins were ligated only segmentally. Finally, the wound was
      approximated while an assistant consistently stretched the penile shaft. The
      operation time was 5.2 to 8.5 hours. The follow-up period ranged from 0.6 to 23.0
      years. Overall, all patients reported satisfactory penile morphology
      postoperatively. In the IIEF group, the difference in preoperative and
      postoperative scores was significant (P < .001). In the non-IIEF group, 2 of the
      3 patients reported natural coitus. This series of salvaging venous surgeries,
      although technically challenging, are helpful in correcting penile deformity and
      restoring erectile function in some patients who had poorer outcomes from prior
      venous surgeries.

PMID- 19745218
TI  - Spermatogenic cycle length and sperm production in a feral pig species (collared
      peccary, Tayassu tajacu).
AB  - Although the collared peccary (Tayassu tajacu) is found throughout the Americas,
      with a high potential for domestication and commercial exploitation, there are
      few data on the reproductive biology of this mammalian species. The aim of the
      present study was to investigate testis structure, spermatogenic cycle length,
      Sertoli cell efficiency, and spermatogenic efficiency. Twelve adult peccaries
      were used for biometrical, histological, and stereological analyses; 3 of these
      peccaries received intratesticular injections of (3)H-thymidine for the
      determination of the duration of spermatogenesis. Testis weight and gonadosomatic
      index were 23.7 +/- 1.8 g and 0.2% +/- 0.1%, respectively. Seminiferous tubule
      volume density was 77.4% +/- 1.7%. Leydig cells occupied 12.8% +/- 1.8% of the
      testis parenchyma and presented a peculiar cytoarchitecture in the periphery of
      the seminiferous tubule lobes. The premeiotic, meiotic, and postmeiotic stage
      frequencies were very similar to those found for wild and domestic boars. The
      spermatogenic cycle and entire spermatogenic process (based on 4.5 cycles) lasted
      approximately 12.3 +/- 0.2 and 55.1 +/- 0.7 days, respectively. Daily sperm
      production per gram of testis in the collared peccary was approximately 23.4 +/-
      2 x 10(6), which is similar to that of domestic and wild boars. The knowledge
      generated in the present study could be used in reproduction and animal
      improvement programs and provides important information that may be used for
      comparative reproductive biology with previously investigated mammalian species.

PMID- 19745219
TI  - Bactericidal/Permeability-increasing protein is associated with the acrosome
      region of rodent epididymal spermatozoa.
AB  - To elucidate the molecular mechanisms involved in sperm maturation during
      epididymal transit, we intended to isolate secretory molecules that are region
      specifically expressed along the epididymis and secreted into the lumen of
      epididymal ducts. By using differential display screening and DNA sequence
      analyses, we isolated a rat bactericidal/permeability-increasing protein (BPI)
      possessing a signal sequence at its N-terminal, which was expressed in the caput
      region of epididymis, but not in the caudal region. Reverse transcription
      polymerase chain reaction analysis and in situ hybridization showed that rat BPI
      messenger RNA (mRNA) was highly expressed in caput epididymal epithelium and that
      its expression level was developmentally up-regulated. Confocal laser scanning
      microscopy with the anti-BPI antibody revealed that in both rats and mice, BPI
      protein was detected on granulelike structures in the lumen of both caput and
      cauda epididymal ducts, as well as at the sperm surface covering the acrosome
      region in spermatozoa freshly isolated from epididymis. Acrosome reaction induced
      by calcium ionophore A23187 in vitro brought about the disappearance of BPI on
      mouse spermatozoa. These data suggested that BPI, which is synthesized in caput
      epididymis and secreted into the lumen, is associated with not only the
      granulelike structures, but also the sperm surface covering the acrosome region,
      and that BPI bound to the acrosome region is extinguished by acrosome reaction.
      Possibly BPI bound to the sperm surface covering the acrosome region in rodent
      spermatozoa is involved in sperm maturation or fertilization.

PMID- 19745220
TI  - Semen quality of male idiopathic infertile smokers and nonsmokers: an
      ultrastructural study.
AB  - This retrospective study was aimed at evaluating the effects of cigarette
      consumption on semen parameters in a group of men with idiopathic infertility.
      The semen quality of 2 groups of men with idiopathic infertility, smokers (n =
      118) and nonsmokers (n = 153), were compared. Conventional semen analysis was
      performed and sperm morphology was assessed by transmission electron microscopy
      (TEM). TEM data were elaborated by means of a mathematical formula based on a
      Bayesian technique able to furnish a fertility index (FI), and the percentages of
      sperm apoptosis, necrosis, and immaturity. Values of normality recommended by
      World Health Organization guidelines were used as a control for conventional
      semen analysis, and values from sperm of 25 men of proven fertility were used for
      TEM indices. Infertile smoker and nonsmoker patients showed similar sperm
      parameters, although sperm motility and TEM analysis values in both groups were
      significantly impaired compared with controls. Smoker patients were then
      classified as mild (>or=1 and <or=10 cigarettes/d), moderate (>10 and <20
      cigarettes/day), or heavy smokers (>or=20 cigarettes/d). Sperm concentration and
      FI were significantly (P < .05) different among the 3 considered smoker classes.
      Comparing the pairs of smoker classes, sperm concentration and FI in heavy
      smokers were significantly lower (P < .05) than that observed in mild smoker and
      nonsmoker groups. Although semen quality in males with idiopathic infertility
      seems not to be dramatically affected by cigarette consumption, heavy smokers
      show significantly lower sperm concentration and FI: another strong reason to
      stop smoking.

PMID- 19745221
TI  - Screening for colorectal cancer in a safety-net health care system: access to
      care is critical and has implications for screening policy.
AB  - BACKGROUND: Data on the number of individuals eligible for screening, and rates
      of screening, are necessary to assess national colorectal cancer screening
      efforts. Such data are sparse for safety-net health systems. METHODS: A
      retrospective cohort study of individuals ages 50 to 75 served by a safety-net
      health system in Tarrant County, TX was conducted to determine (a) the size of
      the potential screen-eligible population ages 50 to 75, (b) the rate of screening
      over 5 years among individuals ages 54 to 75, and (c) the potential predictors of
      screening, including sex, race/ethnicity, insurance status, frequency of
      outpatient visits, and socioeconomic status. RESULTS: Of 28,708 potential screen
      eligible individuals, 20,416 were ages 54 to 75 and analyzed for screening; 22.0%
      were screened within the preceding 5 years. Female gender, Hispanic ethnicity,
      ages 65 to 75, insurance status, and two or more outpatient visits were
      independently associated with screening. Access to care was an important factor:
      adjusted odds ratio, 2.57 (95% confidence interval, 2.23-2.98) for any insurance;
      adjusted odds ratio, 3.53 (95% confidence interval, 3.15-3.97) for two or more
      outpatient visits. CONCLUSIONS: The screen-eligible population served by our
      safety-net health system was large, and the projected deficit in screen rates was
      substantial. Access to care was the dominant predictor of screening
      participation. If our results are replicable in similar health systems, the data
      suggest that screening guidelines and policy efforts must take into account the
      feasibility of proposed interventions. Strong advocacy for more resources for
      colorectal cancer screening interventions (including research into the best
      manner to provide screening for large populations) is needed.

PMID- 19745222
TI  - Chronic periodontitis and the incidence of head and neck squamous cell carcinoma.
AB  - Substantial evidence supports an association between chronic
      infections/inflammation, and cancer. The aim of this study was to assess the
      effect of chronic periodontitis on head and neck squamous cell carcinoma (HNSCC).
      The study population consisted of new patients at the Department of Dentistry and
      Maxillofacial Prosthetics, Roswell Park Cancer Institute between 1999 and 2005.
      Cases were patients diagnosed with primary HNSCC. Controls were all patients seen
      during the same time period but negative for malignancy. Patients age <21 years,
      edentulous, immunocompromised, and those with history of cancer were excluded.
      Periodontitis was measured by alveolar bone loss (ABL) from panoramic radiographs
      by one examiner blind to cancer status. A total of 473 patients (266 cases and
      207 controls) were included in the study. Each millimeter of ABL was associated
      with >4-fold increased risk of HNSCC (odds ratio, 4.36; 95% confidence interval,
      3.16-6.01) after adjustment for age, gender, race/ethnicity, marital status,
      smoking status, alcohol use, and missing teeth. The strength of the association
      was greatest in the oral cavity, followed by oropharynx and larynx. The
      association persisted in subjects who never used tobacco and alcohol. There was a
      significant interaction between smoking and ABL (P = 0.03). Patients with
      periodontitis were more likely to have poorly differentiated oral cavity SCC than
      those without periodontitis (32.8% versus 11.5%; P = 0.038). This study suggests
      that chronic periodontitis is an independent risk factor for HNSCC and smoking
      modifies this association. These results have implications for practical and safe
      strategies for prevention, diagnosis, and treatment of HNSCC.

PMID- 19745224
TI  - Is it time to test metformin in breast cancer prevention trials? A reply to the
      authors.

PMID- 19745226
TI  - [Characterization of an inflammatory response].
AB  - The intensity of an inflammatory response in a tissue or an organ is dependent on
      the efficiency of the organism's homeostatic mechanisms, which restrict the
      extent of the reaction. The type of factor inducing a inflammatory response and
      its strength have significant influence on the dynamics of an inflammatory
      reaction. The prompt eradication of an inflammatory factor and its biologically
      adverse effects attest to the efficacious adaptive mechanisms of the organism.
      The inflammatory response expresses biochemical, hematological, and immunological
      responses at the local or systemic level.

PMID- 19745225
TI  - Molecular identification and functional characterization of Arabidopsis thaliana
      mitochondrial and chloroplastic NAD+ carrier proteins.
AB  - The Arabidopsis thaliana L. genome contains 58 membrane proteins belonging to the
      mitochondrial carrier family. Two mitochondrial carrier family members, here
      named AtNDT1 and AtNDT2, exhibit high structural similarities to the
      mitochondrial nicotinamide adenine dinucleotide (NAD(+)) carrier ScNDT1 from
      bakers' yeast. Expression of AtNDT1 or AtNDT2 restores mitochondrial NAD(+)
      transport activity in a yeast mutant lacking ScNDT. Localization studies with
      green fluorescent protein fusion proteins provided evidence that AtNDT1 resides
      in chloroplasts, whereas only AtNDT2 locates to mitochondria. Heterologous
      expression in Escherichia coli followed by purification, reconstitution in
      proteoliposomes, and uptake experiments revealed that both carriers exhibit a
      submillimolar affinity for NAD(+) and transport this compound in a counter
      exchange mode. Among various substrates ADP and AMP are the most efficient
      counter-exchange substrates for NAD(+). Atndt1- and Atndt2-promoter-GUS plants
      demonstrate that both genes are strongly expressed in developing tissues and in
      particular in highly metabolically active cells. The presence of both carriers is
      discussed with respect to the subcellular localization of de novo NAD(+)
      biosynthesis in plants and with respect to both the NAD(+)-dependent metabolic
      pathways and the redox balance of chloroplasts and mitochondria.

PMID- 19745227
TI  - [BNIP3 as an atypical representative of the Bcl-2 protein family. Part 1: BNIP3,
      a regulator of non-apoptotic programmed cell death].
AB  - BNIP3 is classified as a member of the Bcl-2 protein family that regulates
      programmed cell death and of the BH3-only protein subfamily as it only contains
      one BH domain. However, the transmembrane domain of BNIP3 is involved in at least
      some of its pro-apoptotic functions. Although there are some similarities between
      BNIP3 and other BH3-only proteins, for example the ability to interact with anti
      apoptotic Bcl-2 proteins and to induce cytochrome c release from mitochondria,
      BNIP3 is undoubtedly distinct in regard to its activity and regulatory
      mechanisms. Not only can BNIP3 activate apoptosis, but also, or perhaps first of
      all, it can activate necrosis-like cell death due to its direct interaction with
      the mitochondrial membrane. BNIP3 is also involved is autophagy, but its role in
      this process is not yet clearly understood. It is possible that the induction or
      stimulation of autophagy by this protein can simultaneously inhibit apoptosis,
      for example in cardiac myocytes. In some cells, BNIP3 is sequestered in the
      nucleus, where it also acts as an anti-apoptotic factor, namely as a repressor of
      AIF transcription. This activity may enable tumor cells to achieve resistance to
      chemotherapeutics. Understanding BNIP3 functions and regulatory mechanisms can
      point to new molecular targets in the treatment of cancer and ischemic heart or
      brain diseases.

PMID- 19745228
TI  - [BNIP3 as an atypical representative of the Bcl-2 protein family. Part 2:
      Regulation of the expression and activity of BNIP3 protein and its role in
      tumorigenesis].
AB  - BNIP3 belongs to the Bcl-2 protein family that regulates programmed cell death.
      It is the only known pro-apoptotic protein expressed during hypoxia and this
      effect is determined by the HIF-1 responsive element in the bnip3 promoter.
      However, there is evidence that hypoxia is not a sufficient factor to activate
      BNIP3; possible cell death dependent on this protein occurs as a result of
      secondary effects of oxygen deprivation, such as acidosis. BNIP3 expression is
      also regulated by other factors, such as E2F-1, NF-kappaB, and Rb during hypoxia
      and nitrogen oxide during normoxia. Posttranslational modifications also seem to
      be essential for BNIP3 activity, but their actual significance is still unclear.
      Phosphorylation of BNIP3 by PKC promotes its accumulation under hypoxic
      conditions, but phosphorylation by CK2 can accelerate its degradation. In turn,
      glycosylation and interactions with anti-apoptotic Bcl-2 proteins suppress BNIP3
      activity. Our knowledge about the role of BNIP3 protein in tumor progression is
      incomplete. It seems to be dependent on the stage of tumor progression. Tumor
      cells evolved multiple mechanisms of silencing BNIP3 expression or activity and
      promoter methylation is one of the most frequently observed among them

PMID- 19745229
TI  - The impact of commercial electronic medication management systems on errors and
      clinicians' work in hospitals.

PMID- 19745230
TI  - Patient safety through intelligent procedures in medication: the PSIP project.
AB  - The European project Patient Safety through Intelligent Procedures in medication
      (PSIP) aims at preventing medical errors. The objective are: (1) to facilitate
      the systematic production of epidemiological knowledge on Adverse Drug Events
      (ADE) and (2) to improve the entire medication cycle in a hospital environment.
      The first sub-objective is to produce knowledge on ADE: to know, as exactly as
      possible, per hospital, per medical department, their number, type, consequences
      and causes, including human factors. Data Mining of structured hospital data
      bases, and semantic mining of free-texts will provide a list of observed ADE,
      with frequencies and probabilities, thus giving a better understanding of
      potential risks. The second sub-objective is to develop innovative knowledge
      based on the mining results and to deliver professionals and patients
      contextualized alerts and recommendations fitting the local risk parameters. This
      knowledge will be implemented in a PSIP-Platform independent of existing ICT
      applications.

PMID- 19745231
TI  - Human factors engineering for computer-supported identification and prevention of
      adverse drug events.
AB  - This paper addresses the question of the integration of Human Factors (HF)
      methods and models within projects aiming at (semi-) automatically identifying
      and preventing Adverse Drug Events (ADE). While more traditional methods such as
      voluntary reporting systems of medication errors tend to focus on HF causes of
      preventable ADEs, computer-based screening and mining methods tend to rely on a
      medical model of ADEs. As a consequence, HF methods and concepts are rarely
      considered in those projects. The paper describes the way HF methods have been
      incorporated in the PSIP (Patient Safety through Intelligent Procedures in
      medication) project lifecycle. It provides some examples of the results obtained
      and demonstrates their relevance to improve the entire detection and prevention
      process.

PMID- 19745232
TI  - Decision support to avoid medication errors - how far have we come in Denmark and
      what are the present challenges.
AB  - The number of medication errors reported to The Danish National Board of Health
      in Denmark exceeds 5000 per year. It is well known that computerized physician
      order entry (CPOE) with addition of decision support tools may reduce the
      frequency of medication errors. The primary scope of the work in Denmark has been
      to help health care professionals avoiding harmful errors. Using data primarily
      from The Danish National Board of Health, based on the reports of errors from
      Danish hospitals, and with our previous foundation in the international
      literature, we analyzed the errors which led to harmful conditions or death. In
      the process we developed a methodical consensus for identifying which medicines
      should have a warning attached, and we systematized the different kind of
      warnings. The following validation of the data resulted in a final list of 14
      classes of drugs or drug substances, which all have been involved in serious
      medication errors. At present time there is a total of 136 different medicines
      with warnings found in the drug database for health professionals from Infomatum
      A/S (www.medicin.dk). In a parallel matter other decision support tools from
      Infomatum A/S(2) are available or in progress e.g. ensuring use of correct dosage
      based on normal range, information about drugs used during pregnancy, etc. A
      major challenge when implementing decision support for medication processes has
      been to ensure useful coding of the medicines, A/S there does not exist one
      unique identification number for each drug substance.

PMID- 19745233
TI  - ReMINE: an ontology-based risk management platform.
AB  - The ReMINE project aims at building a high performance prediction, detection and
      monitoring platform for managing Risks against Patient Safety (RAPS). The project
      will contribute to the optimization of RAPS management process in a healthcare
      system through the development of a platform allowing the (semantically based)
      fast and secure extraction of RAPS-related data and their correlation across
      several domains. In this respect the REMINE platform will promote early RAPS
      detection and mitigation by supporting the process of RAPS management both when a
      RAPS is foreseen, and the objective is the determination of the best set of
      preventive actions; and when a RAPS is detected, and the objective is the
      determination of the best possible reaction, the reliable distribution of the
      related action list to all involved parties, and the monitoring of the reaction
      effectiveness. These capabilities will be achieved by means of the establishment
      of an associated methodology and a framework/platform for integrated RAPS
      prediction/detection, analysis and mitigation. The overall platform structure
      assumes the presence of an "info-broker patient safety framework" connected with
      the Hospital Information System, which will support the process of collecting,
      aggregating, mining and assessing related data, distributing alerts, and
      suggesting actions to mitigate (or avoid) RAPS effects or occurrence. The
      underlying ontological system will support the semantic correlation of data with
      the hospital processes.

PMID- 19745234
TI  - The EU-ADR project: preliminary results and perspective.
AB  - The EU-ADR project aims to exploit different European electronic healthcare
      records (EHR) databases for drug safety signal detection. In this paper we
      describe the project framework and the preliminary results. METHODS: As first
      step we created a ranked list of the events that are deemed to be important in
      pharmacovigilance as mining on all possible events was considered to unduly
      increase the number of spurious signals. All the drugs that are potentially
      associated to these events will be detected via data mining techniques. Data
      sources are eight 8 databases in four countries (Denmark, Italy, the Netherlands,
      and the United Kingdom) that are virtually linked through harmonisation of input
      data followed by local elaboration of input data through custom-built software
      (Jerboa). All the identified drug-event associations (signals) will be thereafter
      biologically substantiated and epidemiologically validated. To date, only Upper
      gastrointestinal bleeding (UGIB) event has been used to test the ability of the
      system in signal detection. RESULTS: An initial ranked list comprising 23 adverse
      events was identified. The top-ranking events were: cutaneous bullous eruptions,
      acute renal failure, acute myocardial infarction, anaphylactic shock, and
      rhabdomyolysis. Regarding the UGIB test, a total of 48,016 first-ever episodes
      were identified. The age-standardized incidence rates of UGIB varied between 40
      100/100,000 person-years depending on country and type of healthcare database. A
      statistically significant association between use of NSAIDs and UGIB was detected
      in all of the databases. CONCLUSION: a dynamic ranked list of 23 adverse drug
      events judged as important in pharmacovigilance was created to permit focused
      data mining. Preliminary results on the UGIB event detection demonstrate the
      feasibility of harmonizing various health care databases in different European
      countries through a distributed network approach.

PMID- 19745235
TI  - DebugIT: building a European distributed clinical data mining network to foster
      the fight against microbial diseases.
AB  - The expansion of clinical information systems and the reduction in computing
      costs have led to an explosion of patient data available for reuse. However, this
      data is rarely combined and analyzed in an integrated manner. The DebugIT project
      is a large-scale integrating project funded within the 7th EU Framework Programme
      (FP7). The main objectives of the project are to build IT tools that should have
      significant impacts for the monitoring and the control of infectious diseases and
      antimicrobial resistances in Europe; this will be realized by building a
      technical and semantic infrastructure able to a) share heterogeneous clinical
      data sets from different hospitals in different countries, with different
      languages and legislations; b) analyze large amounts of this clinical data with
      advanced multi-modal data mining; c) apply the obtained knowledge for clinical
      decisions and outcome monitoring. The concepts and architecture underlying this
      project are discussed.

PMID- 19745236
TI  - Detection of adverse drug events: proposal of a data model.
AB  - Our main objective is to detect adverse drug events (ADEs) in former hospital
      stays. As ADEs are rare, that supposes to screen thousands of electronic health
      records (EHRs). For that purpose, we need to define a data model that has two
      main objectives: (1) being able to describe hospital stays from various hospitals
      (2) being tuned so as to prepare the data mining process: as ADEs are not flagged
      in the datasets, the data model must be optimized for ADE detection. The article
      presents the phases of the design and the data model that results from this work.
      It is compatible with many hospitals. It deals with diagnoses, drug
      prescriptions, lab results and administrative information. It allows for data
      mining and ADE detection in EHRs.

PMID- 19745237
TI  - Detection of adverse drug events detection: data aggregation and data mining.
AB  - Adverse drug events (ADEs) are a public health issue. The objective of this work
      is to data-mine electronic health records in order to automatically identify ADEs
      and generate alert rules to prevent those ADEs. The first step of data-mining is
      to transform native and complex data into a set of binary variables that can be
      used as causes and effects. The second step is to identify cause-to-effect
      relationships using statistical methods. After mining 10,500 hospitalizations
      from Denmark and France, we automatically obtain 250 rules, 75 have been
      validated till now. The article details the data aggregation and an example of
      decision tree that allows finding several rules in the field of vitamin K
      antagonists.

PMID- 19745238
TI  - The expert explorer: a tool for hospital data visualization and adverse drug
      event rules validation.
AB  - An important part of adverse drug events (ADEs) detection is the validation of
      the clinical cases and the assessment of the decision rules to detect ADEs. For
      that purpose, a software called "Expert Explorer" has been designed by Ideea
      Advertising. Anonymized datasets have been extracted from hospitals into a common
      repository. The tool has 3 main features. (1) It can display hospital stays in a
      visual and comprehensive way (diagnoses, drugs, lab results, etc.) using tables
      and pretty charts. (2) It allows designing and executing dashboards in order to
      generate knowledge about ADEs. (3) It finally allows uploading decision rules
      obtained from data mining. Experts can then review the rules, the hospital stays
      that match the rules, and finally give their advice thanks to specialized forms.
      Then the rules can be validated, invalidated, or improved (knowledge elicitation
      phase).

PMID- 19745239
TI  - Application of the Apriori algorithm for adverse drug reaction detection.
AB  - The objective of this research is to assess the suitability of the Apriori
      association analysis algorithm for the detection of adverse drug reactions (ADR)
      in health care data. The Apriori algorithm is used to perform association
      analysis on the characteristics of patients, the drugs they are taking, their
      primary diagnosis, co-morbid conditions, and the ADRs or adverse events (AE) they
      experience. This analysis produces association rules that indicate what
      combinations of medications and patient characteristics lead to ADRs. A simple
      data set is used to demonstrate the feasibility and effectiveness of the
      algorithm.

PMID- 19745240
TI  - Adverse drug events prevention rules: multi-site evaluation of rules from various
      sources.
AB  - Adverse drug events are a public health issue (98,000 deaths in the USA every
      year). Some computerized physician order entry (CPOEs) coupled with clinical
      decision support systems (CDSS) allow to prevent ADEs thanks to decision rules.
      Those rules can come from many sources: academic knowledge, record reviews, and
      data mining. Whatever their origin, the rules may induce too numerous alerts of
      poor accuracy when identically applied in different places. In this work we
      formalized rules from various sources in XML and enforced their execution on
      several medical departments to evaluate their local confidence. The article
      details the process and shows examples of evaluated rules from various sources.
      Several needs are enlightened to improve confidences: segmentation,
      contextualization, and evaluation of the rules over time.

PMID- 19745241
TI  - Automatic indexing in a drug information portal.
AB  - OBJECTIVE: The objective of this work is to create a bilingual (French/English)
      Drug Information Portal (DIP), in a multi-terminological context and to emphasize
      its exploitation by an ATC automatic indexing allowing having more pertinent
      information about substances, organs or systems on which drugs act and their
      therapeutic and chemical characteristics. METHODS: The development of the DIP was
      based on the CISMeF portal, which catalogues and indexes the most important and
      quality-controlled sources of institutional health information in French. DIP has
      created specific functionalities and uses specific drugs terminologies such as
      the ATC classification which used to automatic index the DIP resources. RESULTS:
      DIP is the result of collaboration between the CISMeF team and the VIDAL Company,
      specialized in drug information. DIP is conceived to facilitate the user
      information retrieval. The ATC automatic indexing provided relevant results in
      76% of cases. CONCLUSION: Using multi-terminological context and in the framework
      of the drug field, indexing drugs with the appropriate codes or/and terms
      revealed to be very important to have the appropriate information storage and
      retrieval. The main challenge in the coming year is to increase the accuracy of
      the approach.

PMID- 19745242
TI  - Implementation of SNOMED CT to the medicines database of a general hospital.
AB  - A concept-based terminology that covers all features of healthcare is essential
      for the development of an Electronic Health Record (EHR). Since a significant
      percentage of the EHR can be drug related information, we decided to implement
      the controlled drug terminology provided by SNOMED CT to achieve the potential
      benefit to promote Patient Safety that a fully functional pharmacy system can
      offer. One of the expected advantages of our Project is to establish a bridge
      between reference terminology and the drug knowledge databases. There is also an
      economic advantage of implementing a "clinical drug product", the one defined by
      the drug name, its strength and dose form, instead of the manufactured drug
      product. The Pharmacy economic management of stocks and response to the offers
      from the pharmaceutical companies is another expected asset of the Project. This
      Project is intended as well to give support to a more widespread objective of
      interoperability with the Primary Care systems.

PMID- 19745243
TI  - A knowledge engineering framework towards clinical support for adverse drug event
      prevention: the PSIP approach.
AB  - Adverse Drug Events (ADEs) are currently considered as a major public health
      issue, endangering patients' safety and causing significant healthcare costs.
      Several research efforts are currently concentrating on the reduction of
      preventable ADEs by employing Information Technology (IT) solutions, which aim to
      provide healthcare professionals and patients with relevant knowledge and
      decision support tools. In this context, we present a knowledge engineering
      approach towards the construction of a Knowledge-based System (KBS) regarded as
      the core part of a CDSS (Clinical Decision Support System) for ADE prevention,
      all developed in the context of the EU-funded research project PSIP (Patient
      Safety through Intelligent Procedures in Medication). In the current paper, we
      present the knowledge sources considered in PSIP and the implications they pose
      to knowledge engineering, the methodological approach followed, as well as the
      components defining the knowledge engineering framework based on relevant state
      of-the-art technologies and representation formalisms.

PMID- 19745244
TI  - Strategy for implementation and first results of advanced clinical decision
      support in hospital pharmacy practice.
AB  - Clinical decision support systems (CDSS) are the new generation clinical support
      tools that 'make it easy to do it right'. Despite promising results, these
      systems are not common practice, although experts agree that the necessary
      revolution in health care will depend on its implementation. To accelerate
      adoption a strategy is handed for structured development and validation of CDSS'
      content (clinical rules). The first results show that the proposed strategy is
      easily applicable for creating specific and reliable rules, generating relevant
      recommendations.

PMID- 19745245
TI  - Inevitable components of and steps for ADE management systems: the need for a
      Unified Ontological Framework (UOF) and a more effective collaboration in
      medication safety.
AB  - In this article, we will try to address the most basic requirements for
      facilitating the knowledge management challenges through the elaboration of
      medical documentation/ record keeping with several implications on patient
      safety/medication safety and research quality aspects, the main purpose being the
      simplification of utilizing the usable outputs of ontology development efforts.
      This simplification is of vital importance from KM implementation in medical and
      healthcare domains. Because, as Ceusters et al [3] elaborate, reaching consensus
      on even the most basic concepts will become an intricate work in terms of the
      wide-scale implementation of ontology-based KM solutions in clinical practice and
      other healthcare related processes. EHR (Electronic Health Records) standards
      developed by various SDOs are not easy to implement in all circumstances. Any
      implementation effort, not complying with a UOF (Unified Ontological Framework),
      is likely to fail in terms of goal-oriented optimization and high quality safe
      medical practice. World- wide trend is to standardize medical documents focusing
      on the use of terminology systems covering care related processes.

PMID- 19745246
TI  - Computerised Physician Order Entry (CPOE).
AB  - The purpose of this study is to examine how everyday use of the Computerised
      Physician Order Entry (CPOE) system in the Capital Region of Denmark has led to
      medication errors. The study is based on clinicians' reporting of patient safety
      incidents. It was found that the immediate causes of the patient safety incidents
      primarily relates to a) a mismatch between clinical work routines and the
      structure of the CPOE system, b) the complexity of the user interface, and c)
      lack of barriers against commonly occurring, severe errors in some areas of the
      CPOE system. The following was concluded: A well designed CPOE system should be
      intuitive, provide barriers against serious mistakes, and make the correct choice
      an easy one. Furthermore it was concluded that it is important that the CPOE
      system closely supports accepted clinical work routines and that risk assessment
      is performed prior to implementing new design or functionality.

PMID- 19745247
TI  - CPOE, alerts and workflow: taking stock of ten years research at Erasmus MC.
AB  - Ten years ago research of the impact of health information technology (HIT) on
      medical work practices started at Erasmus MC. The research is characterized by
      practice driven field research. From the beginning computerized physician order
      entry systems (CPOE) were a major topic. Research questions were how
      implementation of CPOE could be understood, how physicians were responding to
      reminders and alerts and how CPOE impacted professional workflow and
      collaboration. Studies of CPOE implementation aimed to understand why the
      adoption rate is so low and riddled with difficulties. Studies of reminders and
      alerts addressed the problem of alert fatigue. Finally, studies of workflow
      explored how CPOE influenced clinical workflow and how simplistic and linear
      models underlying CPOE may lead to poor designed systems and even compromise
      patient safety. Findings include the need for a shared understanding of medical
      challenges when implementing CPOE, conceptual models to understand alert fatigue
      and medical workflow and the impossibility of agreeing which alerts to suppress
      hospital-wide. The underlying research principle is the sociotechnical approach,
      which stipulates that technology, people and organizations should be studied from
      a single theoretical framework. This paper summarizes the results of ten years of
      research.

PMID- 19745248
TI  - Contribution of human factors for the review of automatically detected ADE.
AB  - The European project PSIP (Patient Safety through Intelligent Procedures in
      Medication) aims at semi-automatically identifying and preventing ADE.
      Automatically detected Adverse Drug Events have to be reviewed and validated by
      human experts. Existing methods usually have the experts review the cases and
      document their rating in a structured form. One of the limitations of these
      methods is their poor ability to analyze and clear the disagreements between the
      experts and the system. This paper presents an innovative Human Factors based
      method to support the review by clinicians and pharmacologists of these
      automatically detected ADE. We use think aloud methods and portable labs to track
      and record the experts reasoning and their reviewing cognitive procedures. We
      present preliminary results obtained with this method, which allows identifying
      the key data and information used to characterize the ADE. This method provides
      useful feedbacks allowing a continuous refinement and improvement of the
      automated detection system.

PMID- 19745249
TI  - A framework for diagnosing and identifying where technology-induced errors come
      from.
AB  - Health information systems have the ability to reduce medical errors but they can
      also introduce new types of errors. In the cognitive and human factors literature
      there is a recognition that many of the high profile accidents that have occurred
      in other industries outside of healthcare have had their origins in the
      complexities of organizational work and how work is structured. The authors
      propose that in order to have a fully robust framework for diagnosing technology
      induced errors one must understand the development and implementation of a
      technology and the influences of policy using a multi-organizational model. The
      authors propose that technology-induced errors may have their origins in up to
      four or more organizational structures that make up complex health care systems
      in addition to the health care provider: governments, model organizations,
      software development organizations, and local healthcare organizations. In this
      paper a framework for considering the origins of technology-induced error in
      healthcare is presented, along with our experiences to date in the application of
      the framework.

PMID- 19745250
TI  - Gaming against medical errors: methods and results from a design game on CPOE.
AB  - The paper presents design game as a technique for participatory design for a
      Computerized Decision Support System (CDSS) for minimizing medical errors. Design
      game is used as a technique for working with the skills of users, the complexity
      of the use practice and the negotiation of design here within the challenging
      domain of medication. The paper presents a developed design game based on game
      inspiration from a computer game, theoretical inspiration on electronic decision
      support, and empirical grounding in scenarios of medical errors. The game has
      been played in a two-hour workshop with six clinicians. The result is presented
      as a list of central themes for design of CDSS and derived design principles from
      these themes. These principles are currently under further exploration in follow
      up prototype based activities.

PMID- 19745251
TI  - The PSIP approach to account for human factors in Adverse Drug Events:
      preliminary field studies.
AB  - This paper presents a preliminary contribution of a Human Factors (HF) approach
      to prevention of Adverse Drug Events (ADEs), developed within the European
      research project Patient Safety through Intelligent Procedures in medication
      (PSIP). Following an introduction on the role and relevance of HF in ADEs
      prevention, a number of systemic weaknesses encountered during the field activity
      analysis are presented and discussed. Semi-structured interviews and observations
      of medication cycle activities led to infer potential unreliability of some
      decision-making and drug administration procedures. In particular, the usage of
      current electronic support systems emerged as a crucial related element. These
      findings represent an initial contribution which will be further developed within
      PSIP, as HF have been recognised fundamental contributors to ADEs epidemiological
      knowledge and appropriate prevention.

PMID- 19745252
TI  - The problem of defensive medicine: two Italian surveys.
AB  - Defensive medicine takes place when healthcare personnel modify their behaviour
      with the aim of reducing their exposure to legal challenges from patients. The
      phenomenon is directly related to the significant growth in medical malpractice
      litigation over recent years. This article presents the results of two research
      surveys aimed at measuring the extent of defensive behaviours on the part of
      doctors in Italy and at understanding the reasons for them. The first study (the
      National Study (NS) was conducted in respect of a nation-wide sample of general
      practitioners, while the second (the Local Study (LS) was conducted in respect of
      two groups of specialists (surgeons and anaesthetists) in a regional hospital.
      77.9% of the general practitioners interviewed for the NS (responses were
      received from 37% of the 1000 GPs to whom the questionnaire was sent) declared
      that they had practiced at least one form of defensive medicine during the
      previous working month. The figure for the LS was 83.3%. This article discusses
      the factors, such as the blame culture and the increase in medical malpractice
      litigation, that may lead to defensive behaviours and result in negative effects
      both in terms of costs and patient safety. A clear need emerges for a different
      approach to the problem of medical error - at a cultural, organizational and
      legal level - just as in the case of other organizations subject to high risk.
      The deterrent of punishment does not increase the reliability of such
      organizations, nor does it improve the level of safety in them.

PMID- 19745253
TI  - Detection and prevention of Adverse Drug Events - information technologies and
      human factors. Preface.

PMID- 19745254
TI  - After three decades of Medical Informatics Europe congresses.
AB  - European medical informatics professionals traditionally gather at congresses of
      the European Federation for Medical Informatics (EFMI) named "Medical Informatics
      Europe - MIE". After more than three decades of successive organization of these
      congresses, some important points of their history of are presented. As the MIE
      Congress in Sarajevo, organized by the Society for Medical Informatics of Bosnia
      and Herzegovina (BHSMI), is the third EFMI event in the western part of South
      East Europe, a short review of the development of medical informatics in this
      part of Europe, together with important events in its history, will shortly be
      presented.

PMID- 19745255
TI  - Realizing the potential of healthcare information technology to enhance global
      health.
AB  - For much of the world, truly productive and functional Electronic Health Record
      Systems (EHRs) remain an elusive goal of the future. Opportunities abound from
      the visibility provided by the availability of Health Information Technology
      funding in the U.S. and other countries of the world. Now is the time to seize
      the initiative to move from the past to the future to design HIT systems that
      meet the specific needs of each nation of the world in a way that is obtainable
      and affordable, and that provides an immediate return on investment. We need to
      move from an electronic system based on the paper-system to an empowering system
      based on available technology. We need to recognize that the EHR is not just for
      data storage but needs to become an intelligent, active partner with the
      healthcare provider and the patient to enhance health. This paper describes the
      current state of EHRs and addresses challenges for moving into the future.

PMID- 19745256
TI  - Health-enabling technologies for pervasive health care: a pivotal field for
      future medical informatics research education?
AB  - Our societies are changing worldwide. Life expectancy has increased in many
      societies and this increase is often related to an increase in the relative
      amount of elderly persons. Health-enabling technologies are information and
      communication technologies for creating sustainable conditions for self
      sufficient and self-determined lifestyles. Sensor-enhanced health information
      systems play a major role in this context. The question is discussed, whether
      health-enabling technologies for pervasive health care can be regarded as a
      pivotal field for future medical informatics research and education.

PMID- 19745257
TI  - The use of ICT in the delivery of healthcare services to the chronic patient.
AB  - Chronic diseases cause a major problem to the modern health care services world
      wide. Our work describes a new approach to tackle the problem of the chronically
      ill patients, by using information and communication technology (ICT) for
      patient's empowerment and managed their care. Our research, which is conducted
      with close cooperation with the health maintenance organizations and is still
      continuing, is based on a "bottom-up" approach and is also aimed at changing
      paradigms, well established in the western healthcare services.

PMID- 19745258
TI  - Interoperable electronic patient records for health care improvement.
AB  - Pressing needs of cost-effectiveness in healthcare and opportunities of emerging
      electronic health record technologies offer unprecedented chance for progress.
      Ongoing health care improvement and patient safety initiatives demand new
      information collection and communication technologies (e.g., Centers for Medicaid
      and Medicare Services, Joint Commission, National Patient Safety Foundation,
      public health surveillance). Particularly, desire for faster action and cost
      effective health care drive unprecedented investments in electronic patient
      records worldwide. Recognizing these opportunities, many countries and the World
      Health Organization have launched several major health care improvement
      initiatives that are driven by new electronic record technologies. In the United
      States, historic $19 billion investment is provided through the American Recovery
      and Reinvestment Act of 2009. Models of sharing electronic patient data and
      citizen expectations for personal electronic health records will be reviewed.
      Regional health information networks and other information sharing initiatives
      depend on the interoperability of systems. Ultimately, the recent flood of health
      information standards needs to be balanced with actual interoperability
      opportunities. It is anticipated that the current policy discussions on the
      "meaningful use" of electronic health records will have major beneficial
      technical and also reimbursement implications.

PMID- 19745259
TI  - Augmented reality telenavigation in cranio maxillofacial oral surgery.
AB  - Selected workflows combining computer-assisted teleplanning and navigation
      (including 3D-stereolithography) are presented. It is shown how interactive
      teleplanning of dental implants or optimization of a surgical treatment of large
      bone defects is done.

PMID- 19745260
TI  - The clinical decision support consortium.
AB  - Clinical decision support (CDS) can impact the outcomes of care when used at the
      point of care in electronic medical records (EMR). CDS has been shown to increase
      quality and patient safety, improve adherence to guidelines for prevention and
      treatment, and avoid medication errors. Systematic reviews have shown that CDS
      can be useful across a variety of clinical purposes and topics. Despite broad
      national policy objectives to increase EMR adoption in the US, current adoption
      of advanced clinical decision support is limited due to a variety of reasons,
      including: limited implementation of EMR, CPOE, PHR, etc., difficulty developing
      clinical practice guidelines ready for implementation in EMR, lack of standards,
      absence of a central repository or knowledge resource, poor support for CDS in
      commercial EMRs, challenges in integrating CDS into the clinical workflow, and
      limited understanding of organizational and cultural issues relating to clinical
      decision support. To better understand and overcome these barriers, and
      accelerate the translation of clinical practice guideline knowledge into CDS in
      EMRs, the CDS Consortium is established to assess, define, demonstrate, and
      evaluate best practices for knowledge management and clinical decision support in
      healthcare information technology at scale - across multiple ambulatory care
      settings and EHR technology platforms.

PMID- 19745261
TI  - Building eHealth national strategies - the Romanian experience.
AB  - A description of the newest Romanian eHealth project is presented. The SIUI
      project - Integrated Unique Information System of the National Health Insurance
      House was tested on three pilot units in 2007 and generalized in 2008, becoming
      mandatory for all healthcare units in 2009. The implementation process revealed
      some difficulties and the user acceptance is still low. A couple of supporting
      measures, including educational programs, are finally discussed.

PMID- 19745262
TI  - Primary healthcare research network: the Belgian ResoPrim recommendations.
AB  - Dedicated primary care research networks aim to gather and analyse data collected
      from general practioners' (GPs) electronic health records (EHRs). ResoPrim (2003
      2008) was a Belgian multidisciplinary research project which was set up to
      provide recommendations for facilitating the organisation and management of these
      primary care research networks, assessing and improving opportunities for
      researchers working with available data from EHRs, and stimulating the
      involvement of GPs in such networks. This paper provides a short description of
      Resoprim's global methodology (which included 2 pilot phases involving 64 GPs and
      6 different software systems), followed by the project's final recommendations.

PMID- 19745263
TI  - The second generation Slovenian health insurance card.
AB  - Ten years have passed since the design of the Slovenian health insurance card
      system, which has been used daily in the entire Slovenian health sector for the
      last eight years. Eventually, however, a growing number of business and technical
      reasons arose for the gradual renovation of the system. Therefore, in 2006, on
      the basis of a study of feasible solutions, the Health Insurance Institute of
      Slovenia prepared a concept for renovation and began modernising several system
      components, including the new cards as the key security elements of the system.
      In September 2008, the first new professional cards were issued; in November
      2008, the release of the new health insurance cards began.

PMID- 19745264
TI  - On-line data exchange in Slovenian healthcare and health insurance.
AB  - In 2009 the Slovenian healthcare and health insurance sector is implementing a
      national system for the secure on-line exchange of administrative and medical
      data. All general practitioners, hospitals, pharmacies and other healthcare
      providers will connect their information systems to this electronic service.
      Solutions have been built upon, as well as the renovation of the existing well
      recognized national Health Insurance Card System. Using the On-line System,
      health professionals directly access centrally stored patient medical data (data
      on prescriptions issued, on medical technical aids, pregnancy, etc), and a
      comprehensive set of administrative data. The on-line system is a solid
      infrastructure for the further development of applications for direct data
      exchange between the information systems of healthcare providers. It has
      significant benefits for patients, healthcare professionals and health
      administration.

PMID- 19745265
TI  - The development of a Swedish National Information Structure.
AB  - Sweden has as part of its national eHealth strategy decided to develop a generic
      National Information Structure. It is based on three models: The Generic Process,
      Concepts and Information model. The models are intended to be specialised for
      various forms of care including social and community care. The importance of
      interacting models developed in an iterative approach with user involvement is
      emphasised.

PMID- 19745267
TI  - Single source information systems to connect patient care and clinical research.
AB  - Currently documentation processes for routine patient care and clinical research
      are kept separate (dual source). Due to overlaps between routine and research
      documentation, a single source approach provides opportunities to improve
      efficiency of medical documentation given the large workload of physicians
      related to documentation. Organisational, technical and regulatory conditions
      need to be considered for the design of single source systems. We present a
      single source architecture for clinical studies and provide results from pilot
      implementations.

PMID- 19745268
TI  - Linking informaticians and end users - using the STARE-HI evaluation reporting
      framework as a unifying design approach.
AB  - There is understandable concern about low uptake and sub-optimal use of health
      informatics systems, which is often caused by a lack of shared objectives and
      values by the different stakeholders. Moreover, all parties work to different
      ethical codes. For future success, all need to work to the same values and
      objectives, measured by agreed outcomes data, creating robust evidence. The
      Statement on Reporting of Evaluation Studies in Health Informatics (STARE-HI), by
      being recently endorsed by IMIA, EFMI and the EQUATOR Network, may therefore
      provide a generic objectives framework to help achieve common goals.

PMID- 19745269
TI  - The role of a nation-wide information system in improving the access to surgery
      in Portugal.
AB  - This paper describes the design and definitions of an information system (SIGLIC)
      to support a new integrated management program (SIGA) to improve the access to
      surgery in Portugal. SIGIC, the Ministry of Health's agency responsible for
      access to surgery management, started re-thinking the system in 2005 by re
      defining key processes and workflows. The designed information system SIGLIC
      integrates all hospitals with surgery with every other hospital, where it picks
      the data to help manage optimal solutions for each patient. The results since
      2005 are very interesting and show the importance of an integrated information
      system to overcome the bureaucracy in the system: it was noticed a 50%
      improvement in scheduled surgical episodes and a 49% reduction in waiting time.

PMID- 19745270
TI  - ITIL Assessment in a healthcare environment: the role of IT governance at
      Hospital Sao Sebastiao.
AB  - This paper addresses the role of IT Governance in a Hospital Information System
      (HIS) management. ITIL is introduced as a best practice for supporting HIS
      development. Since IT Governance is extensive, we focused our study on an ITIL
      Assessment. The assessment was centred on IT Service Management, and which,
      according to our findings, is being carried inefficiently in Hospital Sao
      Sebastiao. Although the literature quotes the many benefits brought by ITIL to
      the organizations, they all depend on how good the planning and implementing
      processes are. The implementation process itself is very complex and we focused
      our study on the assessment step. The ITIL assessment was crucial to identify IT
      Governance weakness; and it is a way for the organization to become consciousness
      about IT improvement priorities. The results were used to rethink HIS strategy in
      order to properly address the next challenges.

PMID- 19745271
TI  - The importance of timely information in national cancer screening programmes.
AB  - The Ministry of Health of Slovenia decided to support the introduction of two new
      organised screening programmes for cancer, one for breast and the other for colon
      cancer in 2005. This was an addition to the first, already running, programme for
      cervical cancer. Two of them are entrusted to the Institute of Oncology while the
      National CINDI programme takes care of the third one. Besides connection to some
      external public databases, cancer screening programmes require national Cancer
      Registry data. High quality and user friendly information support for citizens
      and medical professionals following doctrinal requirements and possible changes
      is a must.

PMID- 19745272
TI  - Transferring HIS data to population-based cancer registries - concept and first
      implementations.
AB  - Cancer is the second leading cause of death worldwide and in focus of
      epidemiological research. In Germany the cancer registration law stipulates an
      electronic report to the population-based cancer registry (PBCR). In this context
      the Comprehensive Cancer Centre Munster (CCCM) required a new concept to support
      the obligation to register cancer diseases. We analysed Hospital Information
      System (HIS) data structures related to cancer documentation and PBCR documents.
      Our main idea was to export available data items from the HIS and to convert them
      into the import format of the PBCR. We analysed HIS data and developed an XML
      based converter to support an electronic reporting procedure. Using available HIS
      data can avoid redundant data entry and supports information workflow within the
      CCCM. HIS data can provide a secondary use beyond clinical routine in form of
      reporting, quality assurance and clinical research.

PMID- 19745273
TI  - Contribution of record linkage to vital status determination in cancer patients.
AB  - To assess the performance of vital status determination by record linkage between
      a hospital database and the French national mortality database with anonymised
      data in order to adhere to French legislation. Hospital database of the Institut
      Gustave Roussy (IGR), the largest cancer centre in France, and the French
      mortality databases from 1998-2004 were used for this record linkage. A phonetic
      code adapted to French language was first applied to identifiers. The last name,
      maiden name, all first names and the date of birth were then each rendered
      anonymous using irreversible hash coding. Record linkage, using the probabilistic
      method developed by Jaro, was based on four fields: the last name, first given
      name, date of birth and code of birth place. Other variables were used for
      further automatic and manual validation. Linkage results were very satisfactory
      for the 10,089 patients included: sensitivity was 94.8% and specificity 99.5%.
      The positive and negative likelihood ratios were respectively 190 and 0.05. The
      main causes of discordances were erroneous or incomplete information such as
      unrecorded maiden name in the hospital database. Results were improved by adding
      manual validation to electronic matching: sensitivity rose to 97.2% and
      specificity to 99.4%. Record linkage using anonymised data applied to large scale
      hospital data is possible and has good validity. This method offers new prospects
      for large prognostic studies based on hospital data provided that the diagnosis
      date is systematically recorded in the hospital database.

PMID- 19745274
TI  - Foreign currency-related translation complexities in cross-border healthcare
      applications.
AB  - International cross-border private hospital chains need to apply the standards
      for foreign currency translation in order to consolidate the balance sheet and
      income statements. This not only exposes such chains to exchange rate
      fluctuations in different ways, but also creates added requirements for
      enterprise-level IT systems especially when they produce parameters which are
      used to measure the financial and operational performance of the foreign
      subsidiary or the parent hospital. Such systems would need to come to terms with
      the complexities involved in such currency-related translations in order to
      provide the correct data for performance benchmarking.

PMID- 19745275
TI  - A highly scalable information system as extendable framework solution for medical
      R&D projects.
AB  - For research projects in preventive medicine a flexible information management is
      needed that offers a free planning and documentation of project specific
      examinations. The system should allow a simple, preferably automated data
      acquisition from several distributed sources (e.g., mobile sensors, stationary
      diagnostic systems, questionnaires, manual inputs) as well as an effective data
      management, data use and analysis. An information system fulfilling these
      requirements has been developed at the Center for Life Science Automation
      (celisca). This system combines data of multiple investigations and multiple
      devices and displays them on a single screen. The integration of mobile sensor
      systems for comfortable, location-independent capture of time-based physiological
      parameter and the possibility of observation of these measurements directly by
      this system allow new scenarios. The web-based information system presented in
      this paper is configurable by user interfaces. It covers medical process
      descriptions, operative process data visualizations, a user-friendly process data
      processing, modern online interfaces (data bases, web services, XML) as well as a
      comfortable support of extended data analysis with third-party applications.

PMID- 19745276
TI  - Evaluation of an information system model for primary health care.
AB  - Today, at the era of information technologies Bosnia and Herzegovina does not
      have organized action for creation of standardized Computer-Based Information
      Systems (CBISs) in health. These CBISs would enable collection of defined and
      comparable data and therefore ensure adequate analysis, observation and decision
      making on a local community level as well on the general level of health
      information system. Thanks to enthusiasts, local CBISs are created in health care
      facilities. Those individual local CBISs have similar solutions based on the
      experience of previous good functioning. Therefore, we can expect that a
      standardized state CBIS will be formed with the minimal focused action of people
      in charge. The Zavidovici Medical Center has a CBIS which has been working long
      enough so that we can analyze the results of usage of such an information system.
      The system has a modular character, oriented on analysis and documentation of
      data, and on support for management and decision-making functions. Analyzing the
      results reached by implementation of such a CBIS, we can conclude that we have
      achieved better results in patient administration and work organization and that
      we have less patients in dispensary of primary health care by 20%, shorter time
      in treatment of patients by 7%, reduced consumption of essential medicines by 8%,
      costs of treatment in medical facilities are down by 5% and patients have more a
      positive view toward the services provided now than they had earlier. Moreover,
      substantial savings in radio and laboratory diagnostics procedures have been
      achieved by reducing time for doing lab reports, savings in materials and through
      minimizing human error.

PMID- 19745277
TI  - Development of an EHR system for sharing - a semantic perspective.
AB  - Building up Electronic Health Record (EHR) systems is considered a promising
      approach to improve health care quality in China. In order to meet the challenges
      of EHR semantic interoperability, we present a HL7 Clinical Document Architecture
      (CDA) R2 based EHR system prototype developed for Guangdong Hospital of
      Traditional Chinese Medicine (GDHTCM). In particular, we demonstrate how semantic
      technologies are leveraged to benefit EHR users from enabling semantic search
      against an EHR repository. Pilot users of the system deemed it clinically useful,
      which encourages us to develop more capabilities based on EHR in future, like
      cross-institution sharing and integration with a clinical decision support
      system.

PMID- 19745278
TI  - Validation of standardized and structured EHR data in the dual model approach.
AB  - We present a W3C XML Schema-based method to validate standardized EHR data
      against semantic constraints that build the knowledge layer within the dual model
      approach. The approach was tested with three EN/ISO13606 archetypes and an HL7
      CDA implementation guide for diabetes therapies.

PMID- 19745279
TI  - Establishing a personal electronic health record in the Rhine-Neckar region.
AB  - We present an approach to establish a personal and electronic health record
      (PEHR) system in our region, and describe the underlying vision, the technical
      aspects, the current status as well as the gained experiences. Applied are
      international standards (HL7, DICOM) and technologies existing today. Obstacles
      to overcome during the implementation have been the management of access rights,
      data privacy as well as the integration of the primary systems.

PMID- 19745280
TI  - Intelligent consumer-centric electronic medical record.
AB  - Web-based, consumer-centric electronic medical records (CEMRs) are currently
      undergoing widespread deployment. Existing CEMRs, however, have limited
      intelligence and cannot satisfy users' many needs. This paper proposes the
      concept of intelligent CEMR. We introduce and extend expert system and web search
      technology into the CEMR domain. The resulting intelligent CEMRs can
      automatically provide users with personalized healthcare information to
      facilitate their daily activities. We use automatic home medical product
      recommendation as a concrete application to demonstrate the benefits offered by
      intelligent CEMRs.

PMID- 19745281
TI  - Engaging clinicians in clinical content: herding cats or piece of cake?
AB  - It is essential that clinicians are able to contribute to the development of
      clinical content for electronic health records. Clinicians are able to
      participate meaningfully when the technical focus on the process and the clinical
      models are reduced or removed. In the openEHR approach - from the original design
      specification through to the clinical modelling tools - clinicians feature as the
      primary drivers of clinical content models. As tooling develops and matures to
      support authoring, reviewing and publishing of openEHR knowledge artefacts,
      clinicians are increasingly able to be involved - resulting in significant
      contributions to the development of standardized clinical content models which
      will support quality of care for their patients.

PMID- 19745282
TI  - Design of a 'smart' patient record system for mammography patients.
AB  - One of the most common cancer types among women is breast cancer. Regular
      mammographic examinations increase the possibility for early diagnosis and
      treatment and significantly improve the chance of survival for patients with
      breast cancer. Keeping an informed and complete patient record is of great
      importance as the doctor needs this information for every patient examination.
      The proposed implementation is a patient record system that includes 'smart'
      algorithms in order to automatically use data from the patient's record to
      calculate well established epidemiological breast cancer models. A computer-aided
      diagnosis system is also used in order to analyze each mammogram and obtain a
      certain risk percentage concerning whether the patient has to undergo biopsy or
      not. The aforementioned system has been implemented to support a large set of
      patient data (1,178 patients) which included detailed personal patient data,
      medical history and examination details per date and is used in the daily
      clinical practice of a breast cancer diagnostic center facilitating patient
      record retrieval, storage and supporting the doctor's decisions.

PMID- 19745283
TI  - Relevance and management of methylation data in electronic health records.
AB  - In this paper we give an overview of challenges and chances of the integration of
      methylation data into Electronic Health Records. Perspectives of methylation data
      in terms of clinical relevance and characteristics of these data are shown. Among
      several standards OpenEHR, HL7 CG and LOINC are identified as starting point for
      the representation and communication of methylation data within the clinical
      context.

PMID- 19745284
TI  - The electronic health record in Austria: physicians' acceptance is influenced by
      negative emotions.
AB  - Negative emotions like anxiety and fear due to a lack of information may cause
      change barriers and drag physicians' acceptance of the national electronic health
      record (ELGA) in Austria. Qualitative, problem-centric interviews were conducted
      with eight physicians. The results point out that the physicians feel uninformed
      and snubbed. They fear unknown changes, increased costs, workload and
      surveillance without having advantages from using electronic health records in
      their daily practice. Impartial information campaigns, tailored to the
      physicians' needs and questions as well as comprehensive cost-benefit analysis
      could benefit the physicians' opinion of ELGA.

PMID- 19745285
TI  - Integrating clinical theory and practice in an epilepsy-specific electronic
      patient record.
AB  - This study's objective was to assess the usability of the epilepsy history module
      of the electronic patient record, developed at Beaumont Hospital, and to identify
      opportunities for improvement. Observation, interview and document analysis
      methods were used. Results indicated that the module was useable but the design
      did not work as well in practice as anticipated by theory. The next iteration of
      the module included identified enhancements; this iteration is currently in use.

PMID- 19745286
TI  - Software architecture for improving accessibility to medical text-based
      information.
AB  - The paper presents a software architecture aiming to improve accessibility to
      information in specialized texts, with focus on medical texts. This software also
      addresses other problems related to text accessibility such as vision problems
      and language problems. It allows text input in any media format (text, image,
      sound) and outputs the text as digital text or sound, permitting the user to scan
      the medical papers and listen to the translated and adapted text.

PMID- 19745287
TI  - Can openEHR archetypes be used in a national context? The Danish archetype proof
      of-concept project.
AB  - Semantic interoperability and secondary use of data are important informatics
      challenges in modern healthcare. Connected Digital Health Denmark is
      investigating if the openEHR reference model, archetypes and templates could be
      used for representing and exchanging clinical content specification and could
      become a candidate for a national logical infrastructure for semantic
      interoperability. The Danish archetype proof-of-concept project has tried out
      some elements of the openEHR methodology in cooperation with regions and vendors.
      The project has pointed out benefits and challenges using archetypes, and has
      identified barriers that need to be addressed in the next steps.

PMID- 19745288
TI  - A migration to an openEHR-based clinical application.
AB  - MedView is a suit of clinical applications for recording, retrieving and
      visualizing patient records, which has been developed and in use for more than
      ten years. By the introduction of the openEHR architecture, the MedView project
      started an investigation to migrate from its locally developed framework to
      openEHR. Issues related to this process, have been discussed in this paper.

PMID- 19745289
TI  - Implementing an HL7 version 3 modeling tool from an Ecore model.
AB  - One of the main challenges of achieving interoperability using the HL7 V3
      healthcare standard is the lack of clear definition and supporting tools for
      modeling, testing, and conformance checking. Currently, the knowledge defining
      the modeling is scattered around in MIF schemas, tools and specifications or
      simply with the domain experts. Modeling core HL7 concepts, constraints, and
      semantic relationships in Ecore/EMF encapsulates the domain-specific knowledge in
      a transparent way while unifying Java, XML, and UML in an abstract, high-level
      representation. Moreover, persisting and versioning the core HL7 concepts as a
      single Ecore context allows modelers and implementers to create, edit and
      validate message models against a single modeling context. The solution discussed
      in this paper is implemented in the new HL7 Static Model Designer as an
      extensible toolset integrated as a standalone Eclipse RCP application.

PMID- 19745290
TI  - A medical device domain analysis model based on HL7 RIM.
AB  - Clinical investigations (CIs) are carried out to demonstrate safety and efficacy
      of new Medical Devices (MDs). The presence of many stakeholders participating in
      CIs makes it necessary to develop a common standard language to achieve semantic
      interoperability among systems and organizations. In Italy the National Research
      Council is carrying out a project supported by Ministry of Health aiming to
      develop an information system (MEDIS) that manages MD clinical investigations. In
      order to develop a flexible and interoperable system, MEDIS design has been based
      on the application of HL7 (Health Level 7) v.3 standards. This paper presents the
      results of the MEDIS design: the MD DAM based on HL7 RIM.

PMID- 19745291
TI  - Solutions for deploying multi-architecture EHRs on a single EHR educational
      portal.
AB  - In this paper technical issues are discussed related to the development and
      implementation of a remotely accessible portal that allows users to interact with
      a range of electronic health records (EHRs). The Portal (known as the UVic EHR
      Educational Portal) was designed to allow for the hosting of a range of types of
      EHRs, ranging from thick client systems to web-browser-based systems. The portal
      has been successfully deployed to allow simultaneous access by hundreds of users
      (i.e., health professional students) in order to work with representative EHRs
      for educational purposes. The overall architecture is described and issues
      related to the challenges in allowing for the hosting of systems of divers
      designs.

PMID- 19745292
TI  - Biomedical data management: a proposal framework.
AB  - The expansion of biomedical knowledge, reductions in computing costs and spread
      of IT facilities have led to an explosion of the biomedical electronic data.
      However, these data are rarely integrated and analysed because of lack of tools.
      The integration process is complex due to technical and semantic heterogeneity as
      well as lack of reliability in such distributed system. In addition, for the
      specific case of biomedical data, privacy is a crucial constraint. This paper
      presents a pilot system that will be used in the European FP7 DebugIT project to
      integrate biomedical data from several healthcare centres across Europe.

PMID- 19745293
TI  - Building interoperable health information systems using agent and workflow
      technologies.
AB  - Healthcare is an increasingly collaborative enterprise involving many individuals
      and organizations that coordinate their efforts toward promoting quality and
      efficient delivery of healthcare through the use of interoperable healthcare
      information systems. This paper presents a mediator-based approach for achieving
      data and service interoperability among disparate and geographically dispersed
      healthcare information systems. The proposed system architecture enables
      decoupling of the client applications and the server-side implementations while
      it ensures security in all transactions. It is a distributed system architecture
      based on the agent-oriented paradigm for communication and life cycle management
      while interactions are described according to the workflow metaphor. Thus
      robustness, high flexibility and fault tolerance are provided in an environment
      as dynamic and heterogeneous as healthcare.

PMID- 19745294
TI  - Development and validation of strategies to test for interoperability of virtual
      patients.
AB  - Interoperability of e-learning resources requires the adherence to specific
      standards. In the domain of virtual patients (VP) a central role is played by the
      MedBiquitous' MVP specification and its application profile proposed by the eViP
      (Electronic Virtual Patients) project. An important factor in promoting a
      standard is the use of metrics for assessing the conformity of the resources to
      the constraints imposed by the specifications. The overall aim of this study was
      to explore strategies to test for conformance and investigate the capabilities
      and limitations of automated conformance testing. A four-level scale of
      conformance of virtual patient packages to the eViP profile is presented, as well
      as two implementations of conformance testing applications. The developed tools
      have been tested upon level two on a sample of four VP cases acquired from the
      eViP repository of virtual patients.

PMID- 19745295
TI  - A semantic approach for the homogeneous identification of events in eight patient
      databases: a contribution to the European eu-ADR project.
AB  - The overall objective of the eu-ADR project is the design, development, and
      validation of a computerised system that exploits data from electronic health
      records and biomedical databases for the early detection of adverse drug
      reactions. Eight different databases, containing health records of more than 30
      million European citizens, are involved in the project. Unique queries cannot be
      performed across different databases because of their heterogeneity: Medical
      record and Claims databases, four different terminologies for coding diagnoses,
      and two languages for the information described in free text. The aim of our
      study was to provide database owners with a common basis for the construction of
      their queries. Using the UMLS, we provided a list of medical concepts, with their
      corresponding terms and codes in the four terminologies, which should be
      considered to retrieve the relevant information for the events of interest from
      the databases.

PMID- 19745296
TI  - Ontology-driven health information systems architectures.
AB  - Following an architecture vision such as the Generic Component Model (GCM)
      architecture framework, health information systems for supporting personalized
      care have to be based on a component-oriented architecture. Representing concepts
      and their interrelations, the GCM perspectives system architecture, domains, and
      development process can be described by the domains' ontologies. The paper
      introduces ontology principles, ontology references to the GCM as well as some
      practical aspects of ontology-driven approaches to semantically interoperable and
      sustainable health information systems.

PMID- 19745297
TI  - Semantic interoperability between health communication standards through formal
      ontologies.
AB  - The paper shortly analyses the HL7 communication standards for resolving the gap
      between them by developing a set of ontologies reflecting the concepts and
      relationships which is exemplified with the incompatible HL7 versions 2.x and 3.
      Bridging between the different ontologies is performed by introducing a reference
      ontology to which a mapping is defined. The paper discusses problems and
      solutions which appeared during the development process.

PMID- 19745298
TI  - Functional requirements of terminology services for coupling interface
      terminologies to reference terminologies.
AB  - Desiderata for interface terminologies (IT), designed to support interactions
      between humans and structured medical information, differ from desiderata for
      reference terminologies (RT). Terminology experts have recommended that IT be
      mapped to RT. The interface terminology of the Georges Pompidou European Hospital
      (GPEH-IT) contains more than 5,000 concepts, sometimes linked to ICD-10 but not
      yet to the SNOMED 3.5 VF, now available in France. Our objective was to use a
      formal characterization framework to compare GPEH-IT to SNOMED 3.5 VF and to
      define the functionalities of terminology services for managing both IT and RT
      and the mapping between them. We discuss the role of IT and RT in representing
      the meaning of clinical data.

PMID- 19745299
TI  - MediCoordination: a practical approach to interoperability in the Swiss health
      system.
AB  - Interoperability and data exchange between partners in the health sector is seen
      as one of the important domains that can improve care processes and in the long
      run also decrease costs of the health care system. Data exchange can assure that
      the data on the patient are as complete as possible avoiding potential
      mistreatments, and it can avoid double examinations if the data required are
      already available. On the other hand, health data is a sensible point for many
      people and strong protection needs to be implemented to protect patient data
      against misuse as well as tools to let the patient manage his/her own data. Many
      countries have eHealth initiatives in preparation or already implemented.
      However, health data exchange on a large scale still has a fairly long way to go
      as the political processes for global solutions are often complicated. In the
      MediCoordination project a pragmatic approach is selected trying to integrate
      several partners in health care on a regional scale. In parallel with the Swiss
      eHealth strategy that is currently being elaborated by the Swiss confederation,
      particularly medium-sized hospitals and external partners are targeted in
      MediCoordination to implement concrete added-value scenarios of information
      exchange between hospitals and external medical actors.

PMID- 19745300
TI  - An XML schema for automated data integration in a Multi-Source Information System
      dedicated to end-stage renal disease.
AB  - Data exchange and interoperability between clinical information systems represent
      a crucial issue in the context of patient record data collection. An XML
      representation schema adapted to end-stage renal disease (ESRD) patients was
      developed and successfully tested against patient data in the dedicated Multi
      Source Information System (MSIS) active file (more than 16,000 patient records).
      The ESRD-XML-Schema is organized into Schema subsets respecting the coherence of
      the clinical information and enriched with coherent data types. Tests are
      realized against XML-data files generated in conformity with the ESRD-XML Schema.
      Manual tests allowed the XML schema validation of the data format and content.
      Programmatic tests allowed the design of generic XML parsing routines, a portable
      object data model representation and the implementation of automatic data
      exchange flows with the MSIS database system. The ESRD-XML-Schema represents a
      valid framework for data exchange and supports interoperability. Its modular
      design offers opportunity to simplify physicians' multiple tasks in order to
      privilege their clinical work.

PMID- 19745301
TI  - Relationship groups in SNOMED CT.
AB  - Relationship groups are a construct which is particular for the representation of
      concepts in SNOMED CT. In this paper, the July 2008 version of SNOMED CT is
      analyzed to determine the usage of relationship groups. Relationship groups are
      used with 36 out of 65 relations, playing a role in 28% of all concepts.
      Relationship groups are used in the concept types: "procedure" (including
      "regime/therapy"), "finding" (including "disorder"), "situation with explicit
      context" and "specimen". Examples are used to extract the purposes for using role
      groups, after which alternative approaches are discussed. The results indicate
      that relationship groups can be replaced by a small number of types of
      relationships such as "has sign" or "has subprocess".

PMID- 19745302
TI  - Automatic mapping of clinical documentation to SNOMED CT.
AB  - Clinical documentation needs to be fine-grained to truthfully represent the
      history, development, and treatment of a patient. But natural language, as the
      main information carrier, is characterized by many issues, like idiosyncratic
      terminology, spelling and grammar errors, and a lack of grammatical structure.
      Therefore coding systems, like ICD-10, have been introduced, but their use varies
      highly among physicians, and they are often used incompletely or incorrectly. The
      almost exponential growth of clinical data is yet another problem. We present a
      new methodology to process this data: Through combining several natural language
      processing methods we extract morphemes from clinical texts and map them onto
      concepts from SNOMED CT. We first performed a manual analysis of clinical texts
      received from a university hospital and evaluated the issues found in them. Based
      on this we implemented a prototypical system which incorporates both the OpenNLP
      and the MorphoSaurus natural language processing systems.

PMID- 19745303
TI  - Projection and inheritance of SNOMED CT relations between MeSH terms.
AB  - This paper proposes a methodology to achieve the automatic inheritance of SNOMED
      CT relations applied to MeSH preferred terms using UMLS as knowledge source
      server. We propose an interoperability wildcard to achieve this objective. A
      quantitative and a qualitative analysis were performed on top four SNOMED CT
      relations inherited between MeSH preferred terms. A total of 12,030 couples of
      MeSH preferred terms are in relation via at least one SNOMED CT relationship. For
      the top-four relations inherited between MeSH preferred terms, overall 79.25% of
      them are relevant, 16.25% as intermediate and 4.5% as irrelevant, as judged by a
      medical librarian. This work should lead to an optimization of multi-terminology
      indexing tools, multi-terminology information retrieval and navigation among a
      multi-terminology server.

PMID- 19745304
TI  - Optimization of the PubMed Automatic Term Mapping.
AB  - PubMed, freely available on the internet, is the best known database for medical
      information. We propose a method of optimization of the PubMed Automatic Term
      Mapping (ATM) that includes MeSH terms. This method is evaluated using two
      queries constructed to emphasize the differences between the PubMed queries as
      they are at present and also between these queries and the optimized one. The
      proposed query is significantly more precise than the current PubMed query (54.5%
      vs. 27%). The optimized query proposed would be easy to implement into PubMed.

PMID- 19745305
TI  - A reference set of SNOMED terms for the structured representation of respiratory
      disorders of the newborn infant.
AB  - The SNOMED CT(R) July 2006 release was systematically examined using the
      CliniClue(R) terminology browser to identify SNOMED terms that might be relevant
      for the structured representation of respiratory disorders of the newborn infant.
      Three neonatologists evaluated 348 candidate terms for inclusion in a reference
      set. Two hundred and eighty-eight (83%) terms were selected for inclusion. Most
      of the terms (73%) are SNOMED terms that are very relevant for the specific
      domain of care for the newborn infant. Nearly half the terms are fully defined
      and a third have one or more synonyms. The estimated use for the RefSet terms was
      more than once per month for 9% of the SNOMED terms and less than once a year for
      66% of the terms.

PMID- 19745306
TI  - Methods for testing SNOMED CT in a defined clinical domain.
AB  - This paper presents the results of a study in which SNOMED CT has been tested in
      clinical practice by combining quantitative and qualitative methods. An
      application has been developed for registration of vascular diseases and
      procedures using SNOMED CT concepts. We conclude that it requires clinical and
      technical insight to adapt the terminology to a defined clinical domain.

PMID- 19745307
TI  - HL7 template model and EN/ISO 13606 archetype object model - a comparison.
AB  - HL7 Templates and EN/ISO 13606 Archetypes are essential components for a
      semantically interoperable exchange of electronic health record (EHR) data. In
      this article the underlying models from which Templates and Archetypes are
      instantiated, namely the HL7 Template Model and the EN/ISO 13606 Archetype Object
      Model will be compared to identify discrepancies and analogies.

PMID- 19745308
TI  - Comparing the APGAR score representation in HL7 and OpenEHR formalisms.
AB  - Semantic interoperability, a prerequisite to eHealth projects, relies on sharing
      both information and knowledge models between information systems. Two of the
      standards of information models are HL7 v3 and the European norm,
      EN13606/OpenEHR. The paper compares both standards on a fragment of the prenatal
      medical record, the APGAR score. Two factors are compared: the formal
      representation of both information models, and the binding to knowledge models.
      The HL7v3 perinatality DMIM specification and the OpenEHR APGAR archetype were
      used. HL7v3 appears to be more formal than OpenEHR and able to represent in an
      easier way the clinical context. For both standards, the binding to reference
      terminologies such as LOINC is poor. We provide recommendations to improve the
      standards.

PMID- 19745309
TI  - Using the CEN/ISO standard for categorial structure to harmonise the development
      of WHO international terminologies.
AB  - Semantic interoperability (SIOp) is a major issue for health care systems having
      to share information across professionals, teams, legacies, countries, languages
      and citizens. The World Health Organisation (WHO) develops and updates a family
      of health care terminologies (ICD, ICF, ICHI and ICPS) and has embarked on an
      open web-based cooperation to revise ICD 11 using ontology driven tools. The
      International Health Terminology Standard Development Organisation (IHTSDO)
      updates, translates and maps SNOMED CT to ICD 10. We present the application of
      the CEN/ISO standard on categorial structure to bind terminologies and ontologies
      to harmonise and to map between these international terminologies.

PMID- 19745310
TI  - Towards ISO 13606 and openEHR archetype-based semantic interoperability.
AB  - Semantic interoperability of clinical standards is a major challenge in eHealth
      across Europe. It would allow healthcare professionals to manage the complete
      electronic healthcare record of the patient regardless of which institution
      generated each clinical session. Clinical archetypes are fundamental for the
      consecution of semantic interoperability, but they are built for particular
      electronic healthcare record standards. Therefore, methods for transforming
      archetypes between standards are needed. In this work, a method for transforming
      archetypes between ISO 13606 and openEHR, based on Model-Driven Engineering and
      Semantic Web technologies, is presented.

PMID- 19745311
TI  - Clinical laboratory sciences data transmission: the NPU coding system.
AB  - In health care services, technology requires that correct information be duly
      available to professionals, citizens and authorities, worldwide. Thus, clinical
      laboratory sciences require standardized electronic exchanges for results of
      laboratory examinations. The NPU (Nomenclature, Properties and Units) coding
      system provides a terminology for identification of result values (property
      values). It is structured according to BIPM, ISO, IUPAC and IFCC recommendations.
      It uses standard terms for established concepts and structured definitions
      describing: which part of the universe is examined, which component of relevance
      in that part, which kind-of-property is relevant. Unit and specifications can be
      added where relevant [System(spec)-Component(spec); kind-of-property(spec) = ?
      unit]. The English version of this terminology is freely accessible at
      http://dior.imt.liu.se/cnpu/ and http://www.labterm.dk, directly or through the
      IFCC and IUPAC websites. It has been nationally used for more than 10 years in
      Denmark and Sweden and has been translated into 6 other languages. The NPU coding
      system provides a terminology for dedicated kinds-of-property following the
      international recommendations. It fits well in the health network and is freely
      accessible. Clinical laboratory professionals worldwide will find many advantages
      in using the NPU coding system, notably with regards to an accreditation process.

PMID- 19745312
TI  - The role of international classification of diseases in assessment of patients
      with biliary tract disease.
AB  - One of the most common events in Surgical Ward is admission of patients with
      biliary tract disease. To evaluate such patients, it is necessary to create
      appropriate database and define attributes that will be analyzed. The patients
      should be divided in groups for analysis and data processing. There were 219
      patients included in the study. All patients were selected on the basis of ICD-10
      codes and then divided into categories according to the code. In order to assess
      selected patients, the database was created with all relevant questions about
      anamnesis, diagnostic tests and surgical procedures. The data about patients was
      entered into the database. It is possible to analyze data about the most frequent
      disorders of biliary tract. The most common entity was chronic cholecystitis with
      calculus and most common procedure was laparoscopic cholecystectomy. The other
      important attributes are also assessed. ICD-10 classification can be used as a
      basis for aggregation of data of the patients with biliary tract disease. Some of
      the codes are more frequent than others and some are rarely used.

PMID- 19745313
TI  - Social care informatics - the missing partner in ehealth.
AB  - To the individual, social care can be an essential part of maintaining health, as
      is reflected by the WHO definition of health as being one of wellbeing. However,
      health informatics currently narrowly restricts itself to health organizations'
      activities. Digital records in social care are increasing, raising the need to
      recognize the area of social care informatics. This new domain needs support and
      nurture, whilst the delivery of social and related care needs to be harmonized
      with healthcare delivery. In turn, this raises important new issues as to how to
      best support the citizen, especially when they are dependent, including issues of
      information sharing, service co-ordination, sharing of meaning and objectives,
      and of respect for autonomy.

PMID- 19745314
TI  - Informal social networks amongst administrative staff at a university hospital.
AB  - In this study we apply Social Network Analysis and Agent Based Simulation
      techniques to visualize and explore informal social networks amongst staff at the
      Akdeniz University Hospital to assess and evaluate properties of the organization
      in terms of its ability to share knowledge and innovate, which is crucial for
      healthcare organizations delivering a health service. We first prepared an e-mail
      based questionnaire, and asked administrative staff at Akdeniz University
      Hospital, a number of questions including (i) who they would contact if they had
      an innovative idea regarding their work (ii) who they would consult if they
      wanted to implement their idea, and (iii) to whom they would talk when they
      wanted to find out what is going on socially in the work place. We use a bespoke
      software tool called Organizational Forms Simulator to visualize and analyze
      informal social networks obtained from the questionnaire. The analysis reveals
      hubs, lynchpins, and unknown leaders as well as communications bottlenecks, and
      overall connectivity in the organization. The software tool we use also allows us
      to run what-if scenarios, to see how long it would take for an 'epidemic' of a
      good idea to spread across the staff social networks, using the informal links
      obtained from the questionnaire. We believe the study will help us to assess the
      current state of informal social networks amongst staff, and help the hospital
      management to improve connectivity in the organization.

PMID- 19745315
TI  - Knowledge sharing for pediatric pain management via a Web 2.0 framework.
AB  - The experiential knowledge of pediatric health practitioners encompasses vital
      insights into the clinical efficacy of diagnostic and therapeutic methods for
      pediatric pain management. Yet, this knowledge is not readily disseminated to
      other practitioners and translated into practice guidelines. We argue that a peer
      to-peer knowledge sharing mechanism can serve as a key change agent to improve
      the attitudes, beliefs and methods for pediatric pain management. We are using
      collaborative technologies, in the realm of Web 2.0, to develop a web-based
      knowledge sharing medium for fostering a community of pediatric pain
      practitioners that engages in collaborative learning and problem solving. We
      present the design and use of a web portal featuring a discussion forum to
      facilitate experiential knowledge sharing based on our LINKS knowledge sharing
      model.

PMID- 19745316
TI  - An analysis of personal medical information disclosed in YouTube videos created
      by patients with multiple sclerosis.
AB  - The Internet has become one of the main sources of health information. Today,
      content generation is no longer limited to the healthcare professionals of the
      late nineties; Web 2.0 services and platforms have empowered patients to create
      and interact with various forms of Patient-Generated Content (PGC); these
      include: videos, blogs, and social networking pages, among others. This
      investigation evaluated the characteristics of PGC found within YouTube video
      comments. We selected a random sample of 25 out of 769 Multiple Sclerosis patient
      generated videos and analyzed their corresponding 557 comments for health
      information. 320 comments met the inclusion criteria and 70 contained personal
      health information (PHI). Comments with PHI were sub-characterized for the type
      of medical information (i.e., diagnosis, date of diagnosis, medication, among
      others). In this descriptive study, we present the strata within this content and
      postulate some of the corresponding patient risks and ethical challenges
      associated with PGC found in YouTube video comments.

PMID- 19745317
TI  - eHealth tools for patients and professionals in a multicultural world.
AB  - In many countries today, an important challenge for health care is the fact that
      the population is mixed as regards cultural background and not the least with
      regard to preferred language. In our country Sweden almost 20% of the population
      has some connection to another country and many patients seeking health care do
      not have sufficient mastering of the dominant Swedish language to get optimal
      care. We propose in this study a set of eHealth services that could be
      implemented within a country and in multinational co-operation to deal with some
      of these issues in an effective way which both empowers the citizens, improves
      patient safety and at the same time may offer cost savings for the publicly
      financed health care systems in the countries of the European Union. The basic
      idea is to use a set of people-people communication strategies using ICT tools
      combined with semantic tools for information sharing and conversion. This
      requires new and challenging organizational contexts.

PMID- 19745318
TI  - Web-based resources for peer support - opportunities and challenges.
AB  - Social software and Web 2.0 provides new opportunities for participation and
      collaborative knowledge construction in peer support and self-care to live well
      despite transient or permanent health problems. Opportunities include many to
      many interactions to share and accumulate knowledge and experiences from several
      perspectives. We are conducting a study to create a collaborative environment for
      peer support and knowledge construction related to a rare condition. The study
      draws from participatory design and agile approach to development; extensively
      using design workshops and iterative prototyping. Several workshops led to
      systematize perspectives of different participant groups, and provided feedback
      about functionalities illustrated in different mock-ups and prototypes. Here we
      report experiences, and focus on feedback from participants leading to special
      considerations in design of the web-based environment.

PMID- 19745319
TI  - Organizational vs. technical variables: impact on the collective aspects of
      healthcare work situations.
AB  - This study addresses the question of the respective impact of organizational vs.
      technical environment variables on the collective aspects of healthcare work
      situations. It analyzes the physicians-nurses communications during the
      medication use process, according to both the organization of their work and
      their technical environment. It demonstrates that the organizational variables
      have a larger impact than the technical environment on the communications and
      cooperation activities.

PMID- 19745320
TI  - Relevance of Google-customized search engine vs. CISMeF quality-controlled health
      gateway.
AB  - CISMeF (acronym for Catalog and Index of French Language Health Resources on the
      Internet) is a quality-controlled health gateway conceived to catalog and index
      the most important and quality-controlled sources of institutional health
      information in French. The goal of this study is to compare the relevance of
      results provided by this gateway from a small set of documents selected and
      described by human experts to those provided by a search engine from a large set
      of automatically indexed and ranked resources. The Google-Customized search
      engine (CSE) was used. The evaluation was made using the 10th first results of 15
      queries and two blinded physician evaluators. There was no significant difference
      between the relevance of information retrieval in CISMeF and Google CSE. In
      conclusion, automatic indexing does not lead to lower relevance than a manual
      MeSH indexing and may help to cope with the increasing number of references to be
      indexed in a controlled health quality gateway.

PMID- 19745321
TI  - Entrez Neuron RDFa: a pragmatic semantic web application for data integration in
      neuroscience research.
AB  - The amount of biomedical data available in Semantic Web formats has been rapidly
      growing in recent years. While these formats are machine-friendly, user-friendly
      web interfaces allowing easy querying of these data are typically lacking. We
      present "Entrez Neuron", a pilot neuron-centric interface that allows for keyword
      based queries against a coherent repository of OWL ontologies. These ontologies
      describe neuronal structures, physiology, mathematical models and microscopy
      images. The returned query results are organized hierarchically according to
      brain architecture. Where possible, the application makes use of entities from
      the Open Biomedical Ontologies (OBO) and the 'HCLS knowledgebase' developed by
      the W3C Interest Group for Health Care and Life Science. It makes use of the
      emerging RDFa standard to embed ontology fragments and semantic annotations
      within its HTML-based user interface. The application and underlying ontologies
      demonstrate how Semantic Web technologies can be used for information integration
      within a curated information repository and between curated information
      repositories. It also demonstrates how information integration can be
      accomplished on the client side, through simple copying and pasting of portions
      of documents that contain RDFa markup.

PMID- 19745322
TI  - Towards a semantic framework for an integrative description of neuroscience
      patterns and studies: a case for emotion-related data.
AB  - The continuously increasing number of neuroscience studies and the difficulties
      associated with searching for related information and properly tracking
      neuroscience findings makes it imperative that one may be lead to isolated
      theories and findings which may be incompatible to each other or partially
      occluded. Semantically describing several aspects of studies in this field, such
      as, research groups attributes, aims of studies, experimental procedures
      followed, hardware and software tools utilised, acquisition systems used, as well
      as, the emerging neuro-physiological patterns found, may facilitate an
      integrative view of neuroscience theories. To this end, the current piece of work
      aims to provide a global theoretical framework using ontologies and semantic
      rules to describe neuroscience studies. Implementation details and applicability
      of the proof of concept are illustrated by means of an example targeting the
      semantic description of an emotion related study. The importance of the proposed
      framework in facilitating the envisaged personalised healthcare of the
      information society is discussed.

PMID- 19745323
TI  - Electronic referrals in healthcare: a review.
AB  - This paper gives an overview of projects completed on the topic of electronic
      referral in healthcare. The first referral projects were based on standardized
      EDI-communication. The same basis is still used in many projects, but these are
      slowly being replaced by web-based solutions with possibilities for decision
      support and booking. The time from initiation of the first services to high
      volume use seems to be very much related to how well the new solutions fit with
      the general practitioners and specialists work practices, and if there are
      obvious benefits for the communication partners. High volume national services
      seem to require both political support and pressure. Some of the projects have
      not paid enough attention to sociotechnical approaches.

PMID- 19745324
TI  - Task analysis and application services for cross-organizational scheduling and
      citizen eBooking.
AB  - In this paper, we present generalized results from the task analysis and
      definition of software services to support healthcare appointment and services
      scheduling, based on national coordination project for citizen e-services in
      Finland which involves several regional initiatives. The results are part of
      guidelines for regional-level and national-level scheduling solutions in Finland,
      and can be used in similar efforts. The specification of a functional reference
      model and software services for appointment scheduling promotes interoperability
      and systems adaptability for the transformation of health services and citizen
      empowerment.

PMID- 19745325
TI  - KernPaeP - a web-based pediatric palliative documentation system for home care.
AB  - KernPaeP is a new web-based on- and offline documentation system, which has been
      developed for pediatric palliative care-teams supporting patient documentation
      and communication among health care professionals. It provides a reliable system
      making fast and secure home care documentation possible. KernPaeP is accessible
      online by registered users using any web-browser. Home care teams use an offline
      version of KernPaeP running on a netbook for patient documentation on site.
      Identifying and medical patient data are strictly separated and stored on two
      database servers. The system offers a stable, enhanced two-way algorithm for
      synchronization between the offline component and the central database servers.
      KernPaeP is implemented meeting highest security standards while still
      maintaining high usability. The web-based documentation system allows ubiquitous
      and immediate access to patient data. Sumptuous paper work is replaced by secure
      and comprehensive electronic documentation. KernPaeP helps saving time and
      improving the quality of documentation. Due to development in close cooperation
      with pediatric palliative professionals, KernPaeP fulfils the broad needs of home
      care documentation. The technique of web-based online and offline documentation
      is in general applicable for arbitrary home care scenarios.

PMID- 19745326
TI  - Development and evaluation of a patient information website for childhood cancer
      survivors.
AB  - Usability evaluation is an essential step in health care system development,
      including patient information websites. In this study we compared the think aloud
      method (TA) and the heuristic evaluation (HE) in a case study on the development
      of a website for childhood cancer survivors. Both methods managed to uncover all
      major problems with the website, though additionally HE found cosmetic issues and
      the TA found problems with website content. These findings contradict earlier
      studies but may be explained by the inclusion of two double experts in our study,
      presumably enabling them to take on the role of 'a patient' in testing the
      website. We nevertheless recommend the use of both methods if adequate funding
      and expertise are available; otherwise when HE usability evaluators are not
      familiar with the system domain, a work-domain expert could assist them in
      tackling domain-specific problems.

PMID- 19745327
TI  - Screen complexity of Italian institutional cancer web sites.
AB  - The discordant results of a comparison between calculated and perceived screen
      complexity of 14 Italian Institutional Cancer Web Sites are described here.

PMID- 19745328
TI  - An openEHR-based clinical decision support system: a case study.
AB  - Experiences in developing a Clinical Decision Support System (CDSS) for dry mouth
      revealed that traditional approaches for creating clinical applications are not
      suitable because of the lack of structured knowledge in the domain and the
      complex nature of existing knowledge. Nevertheless, openEHR offers various
      benefits. This paper presents the issues related to developing an openEHR-based
      CDSS for this disease.

PMID- 19745329
TI  - New patient interaction formulas in Spanish and Catalan: a case for forumclinic.
AB  - On February of 2007, forumclinic (www.forumclinic.org) was launched. This free,
      first of its kind, collection of Evidence-Based Medicine chronic disease
      monograph resources, is targeted for Spanish and Catalan-speaking patients.
      Information is available both online (i.e., forums) and offline (i.e., DVDs) and
      is culturally sensitive to the target population. Forumclinic has cantered on
      active patient engagement through the use of disease-specialist moderated forms.
      Both the Health on the Net Foundation and the Medical Doctors College of
      Barcelona have accredited forumclinic as a quality, unbiased, health site that is
      based on the WHO premise of Social Determinants of Health - increased health
      education and interaction leads to better health. This descriptive paper will
      introduce forumclinic and describe the patient/user response to date.

PMID- 19745330
TI  - The use of open source and Web2.0 in developing an integrated EHR and e-learning
      system for the Greek Smoking Cessation Network.
AB  - Technologies of information and communication are incrementally integrated with
      all facets of healthcare practice and education. Although Electronic Health
      Records (EHRs) have long been used in healthcare the introduction of open source
      tools has empowered their further expansion of use. Simultaneously the use of Web
      2.0 tools has opened up new ways of enhancing both healthcare practice and
      education. In this paper, we describe our approach towards the development of an
      integrated system supporting the smoking cessation network initiatives in the
      Greek public hospitals. The system combines the availability of an open source,
      web based EHR subsystem, with a Web 2.0 facilitated e-learning component for
      supporting continuing medical education and promoting public awareness.

PMID- 19745331
TI  - Comparative study between expert and non-expert biomedical writings: their
      morphology and semantics.
AB  - The amount of health information on the internet is constantly growing but little
      is done for detecting the technicality level of these documents and guiding of
      users towards documents which are appropriate to their expertise level. The
      objective of our work is to propose clues for the automatic distinction between
      expert and non expert medical documents. More precisely, we propose to study
      their morphological and semantic levels. We apply NLP tools, which provide access
      to the morpho-semantic content of documents. The work is done with French
      documents within three medical fields (cardiology, pneumology, diabetes). Our
      experiments and results highlight the fact that this level can indeed provide
      clues for the distinction of the technicality of documents, and that they appear
      to be significant and stable across the studied medical fields.

PMID- 19745332
TI  - Designing an e-health application in collaboration with obesity patients.
AB  - Maintaining healthy behavior among obesity patients is a challenge. This study
      aims to design an electronic health application for self-care management in
      collaboration with obesity patients and healthcare personnel.

PMID- 19745333
TI  - Improving cardiology workflow in a hospital using a mobile software solution.
AB  - The paper presents a study and a software solution to support the cardiology
      department in a hospital. The result is quicker access to patient data and better
      management of the activities of the nurses. Alarms are sent on the spot and
      reaction is immediate, providing optimization of the process. The improvements in
      the activity of the cardiology department will raise the quality of the medical
      process with great benefits for the patient.

PMID- 19745334
TI  - Interoperability services in the MPOWER Ambient Assisted Living platform.
AB  - Ambient Assisted Living systems for the ageing and cognitively disabled do not
      exist in isolation. What characterizes such systems is the cooperation of several
      different stakeholders in the care process and the service platforms need to
      address this. This paper reports on our work in the EU IST MPOWER project where
      we have designed and implemented interoperability services based on patterns,
      service-oriented architectures, web services and XSDL transformations. The
      services we present are freely available as open source under the MIT license.

PMID- 19745335
TI  - Trauma Network North-West - improving holistic care for trauma patients by means
      of internet and mobile technologies.
AB  - The Trauma Network North-West as an initiative seeks to improve the initial and
      follow-up care for severely injured patients in need of immediate intensive care.
      The main goals are intensification and optimization of exchange of information,
      expertise and knowledge among participating clinics. By (a) foundation of the
      network itself and (b) establishment of a sophisticated IT infrastructure for web
      based and mobile communication, instantaneous and concomitant care for trauma
      patients shall be significantly improved. The network's workflow incorporates
      participating clinics within a central platform, including parameters such as
      level of health care, geographic coordinates, overstrained care units and
      defective medical devices. Mobile components allow locating nearby clinics based
      on an emergency physician's coordinates and automatic triggering of disposition
      via coordination offices. A tight interplay between server components and
      location-based services shall reduce unnecessary transportation as well as
      financial expenditure. The central web-based system is currently established and
      evaluated in an initial test phase.

PMID- 19745336
TI  - Information systems for administration, clinical documentation and quality
      assurance in an Austrian disease management programme.
AB  - 5.9% of the Austrian population is affected by diabetes mellitus. Disease
      Management is a structured treatment approach that is suitable for application to
      the diabetes mellitus area and often is supported by information technology. This
      article describes the information systems developed and implemented in the
      Austrian disease management programme for type 2 diabetes. Several workflows for
      administration as well as for clinical documentation have been implemented
      utilizing the Austrian e-Health infrastructure. De-identified clinical data is
      available for creating feedback reports for providers and programme evaluation.

PMID- 19745337
TI  - Requirements regarding quality certification of Electronic Health Records.
AB  - Quality assurance is a major task with regard to the implementation of Electronic
      Health Records (EHRs). Currently there are only a few approaches explicitly
      dealing with the quality of EHR services. The objective of this paper is to
      present the results of an expert survey that was conducted in 2008 including 29
      experts from various European countries and different areas. The experts were
      questioned about requirements regarding quality certification, important areas
      for certification, known certifications and important sources for the
      establishment of a certification. The results clearly showed, that there is the
      need for certification and confirmed the initial assumption that additional
      research has to be conducted in this field.

PMID- 19745338
TI  - Clinical and statistical evaluation of 1st Automatic: a pilot study.
AB  - Arterial blood gas analyses provide information about the patient's oxygenation,
      ventilation, and perfusion. Studies have shown that most errors occur during the
      pre-analytical phase (the processes prior to the actual analysis of the sample).
      1st Automatic is an extra module to the existing blood gas analyzer and a partial
      automation of the pre-analytical phase which is designed to reduce these errors.
      The objective was to investigate whether 1st Automatic is compatible to the
      conventional method. Quantitative measurements of pH, pCO2, pO2, Na+, K+, Ca2+,
      cGlu, cLac and tHb were performed on 21 paired whole blood specimens collected
      into the standard blood gas syringes and safePICO syringes, both designed for the
      ABL800 FLEX. During the collection the pre-analytical errors were minimised. No
      clinically significant differences were observed in the nine blood gas
      parameters. The differences were statistically insignificant, with the exception
      of cNa+, cCa2+ and tHb. There was a good consistency between the results using
      the new automated procedure and the conventional method. It was not possible to
      show any clinically significant difference between the two procedures.

PMID- 19745339
TI  - Adopting software quality measures for healthcare processes.
AB  - In this study, we investigated the adoptability of software quality measures for
      healthcare process measurement. Quality measures of ISO/IEC 9126 are redefined
      from a process perspective to build a generic healthcare process quality
      measurement model. Case study research method is used, and the model is applied
      to a public hospital's Entry to Care process. After the application, weak and
      strong aspects of the process can be easily observed. Access audibility, fault
      removal, completeness of documentation, and machine utilization are weak aspects
      and these aspects are the candidates for process improvement. On the other hand,
      functional completeness, fault ratio, input validity checking, response time, and
      throughput time are the strong aspects of the process.

PMID- 19745340
TI  - An RDF-based mediator for health data interoperability.
AB  - In this paper the authors propose and describe a Resource Description Framework
      (RDF)-based mediator designed to solve the health data interoperability problem
      that exists among heterogeneous health information systems (e.g., Electronic
      Health Records). The RDF-based mediator framework has three main components: (1)
      the Synonym Dictionary (SD) that can be used to map metadata semantics, (2) the
      CXTR module that can translate source XML-based health documents into RDF-XML
      format, and (3) the CRTX module that can translate an RDF-XML document into a
      target XML-based health document. The proposed mediator is expected to make
      health information exchange more efficient.

PMID- 19745341
TI  - Usability laboratory as the last outpost before implementation - lessons learnt
      from testing new patient record functionality.
AB  - The implementation of clinical IT systems is resource-demanding and difficult. In
      this paper we show how laboratory-based usability tests can be used as a last
      checkpoint before a system is rolled out, and share lessons learnt on how to
      conduct such tests in order to obtain valid results. The recommendations are
      based on experiences from two usability tests of a new medication module
      conducted in the spring 2008, where two nurses and two physicians simulated a pre
      round meeting, ward round, and administration of medication in a usability lab
      furnished as a hospital ward. The results show that details around the test
      situation are important for testing of implementation ready clinical IT systems.
      Patient cases must be adapted to the clinical specialties of the test
      participants, the patient data in the system must be complete, and persons
      holding the roles as patients have to understand the patient histories and the
      medical problem.

PMID- 19745342
TI  - Foundations of a metadata repository for databases of registers and trials.
AB  - The planning of case report forms (CRFs) in clinical trials or databases in
      registers is mostly an informal process starting from scratch involving domain
      experts, biometricians, and documentation specialists. The Telematikplattform fur
      Medizinische Forschungsnetze, an umbrella organization for medical research in
      Germany, aims at supporting and improving this process with a metadata
      repository, covering the variables and value lists used in databases of registers
      and trials. The use cases for the metadata repository range from a specification
      of case report forms to the harmonization of variable collections, variables, and
      value lists through a formal review. The warehouse used for the storage of the
      metadata should at least fulfill the definition of part 3 "Registry metamodel and
      basic attributes" of ISO/IEC 11179 Information technology - Metadata registries.
      An implementation of the metadata repository should offer an import and export of
      metadata in the Operational Data Model standard of the Clinical Data Interchange
      Standards Consortium. It will facilitate the creation of CRFs and data models,
      improve the quality of CRFs and data models, support the harmonization of
      variables and value lists, and support the mapping of metadata and data.

PMID- 19745343
TI  - Inter-institutional care process: scenarios to capture demands for workflow
      support.
AB  - Care processes across hospitals challenge healthcare information systems. Shared
      care scenarios ensure the insight from different perspectives on detailed demands
      for workflow support in a changing clinical practice.

PMID- 19745344
TI  - Issues on evaluating the usability of a pen-tablet system using server-based
      computing.
AB  - The purpose of this study is to define the issues in evaluating the usability of
      pen-tablet systems (PTS) with server-based computing (SBC) in hospital settings.
      For five subjects with PTS operation, we measured the delay of drawing under SBC
      environments and compared it with the results of questionnaires from subjects. It
      was found that the relation of the usability with the drawing velocity and the
      delay is the crucial issue for a further study.

PMID- 19745345
TI  - Integrating A3 reports and the House of Quality: improving workflow in the
      recovery room using information technology.
AB  - In this paper, we provide a methodology for integrating the House of Quality
      (HOQ), a process tool, with Toyota A3 reports to effectively identify the
      priorities and root causes of poor efficiency in a Post Anesthesia Care Unit's
      (PACU) workflow. The A3 report allowed us to identify the workflow waste, and the
      HOQ helped us to identify and prioritize the critical root causes of poor
      workflow that could be improved by technology.

PMID- 19745346
TI  - Bridging the gap between patients' expectations and general practitioners'
      knowledge through disease surveillance.
AB  - In this paper we have investigated "to what degree patients trust their regular
      doctor to be fully informed about the prevalence of infectious diseases in their
      neighbourhood", and what general practitioners (GPs) actually know. A
      representative sample of one thousand Norwegians (potential patients) was
      interviewed by telephone, and 13 GPs were interviewed individually or in focus
      groups. Nearly half of the patients trusted their GP to be more or less "fully
      informed" about the prevalence of infectious diseases in their neighbourhoods,
      while the GPs in reality were not well informed. We conclude that new
      surveillance solutions are needed. One promising approach is electronic retrieval
      of symptom data directly from patients.

PMID- 19745347
TI  - Navigation for people with mild dementia.
AB  - Community dwelling is a problem for people with dementia. Can GPS route
      navigation support on a mobile device provide a solution? In a small scale
      exploratory research with this target group we studied the effects of two
      different types of audio instructions and assessed the pedestrian safety while
      operating the device. Methodological issues that limited the size and scope of
      data collection notwithstanding, evidence of unsafe behaviour was not found.
      Navigation instructions spoken by a familiar voice seemed to have a positive
      impact on the effectiveness of the navigation system, while the use of warning
      sounds seemed to have the opposite effect.

PMID- 19745348
TI  - Application of simple digital methods in the treatment of hemorrhoid disease.
AB  - The treatment of patient with relapse of bleeding after application of minimally
      invasive treatment of hemorrhoidal disease such as elastic band ligation,
      cryosurgical treatment Hemorrhoidal Arterial Ligation (HAL) can be presented as
      serious clinical problem in patients with concomitant diseases that can be
      contraindication for radical surgical treatment. We compared the Simple Digital
      Method and standard above mentioned minimally invasive ambulatory treatment. We
      used special proctoscope with Doppler Flowmeter in order to identify all branches
      of hemorrhoidal artery in the anal canal creating graphical presentation using
      specially adapted software. HAL method is then used to perform ligation of
      hemorrhoidal artery branches. The elastic ligatures (called gummiligatures) are
      then applied to the piles in which most prominent flow was registered using
      Doppler Flowmeter. Antibiotic prophylaxis and sedation was administered
      preoperatively. Special computer program registered all steps. Hemorrhoidal
      ointments and paracetamol were used after surgical procedure. Average number of
      identified hemorrhoid arteries branches was six, and total duration of the
      procedure was in average 28 min. We compared patient treatment with our method
      and standard methods. In tested group we noticed significantly fewer
      complications (after eight days the number of complications 11% vs. 74%, p<0.001,
      after 15 days 3% vs. 11%: p=0.101). One year after procedure, the treatment was
      successful in 91.4%, or 32 out of 35 patients according to proctoscopy and
      Doppler Flowmeter exam. There were three patients with relapse of symptoms. In
      77% of patients hat were treated with rubber bands ligation relapse occurred. Our
      method is significantly more successful in comparison to classical methods of
      ambulatory treatment and can be alternative to radical surgical treatment.

PMID- 19745349
TI  - Towards a framework for better management of patients with hypertension.
AB  - Management of patients with hypertension is poor and novel tools are needed to
      identify patients whose clinical outcomes can be improved. We herein present a
      framework we have developed that can be used to identify patients who meet
      specific audit criteria related to poor management of hypertension. Identified
      patients would benefit from an immediate follow-up by a practice nurse.

PMID- 19745350
TI  - A home-care PDA-based program for the management of COPD patients.
AB  - This paper proposes a PDA-based system, SERVANDO, for the home-care management of
      patients with COPD. In addition to making the supervision of such patients
      easier, the system permits the collection and structuring of large quantities of
      information on the evolution of COPD, allowing the application of data-mining
      techniques, which could open up new lines of research on this disease.

PMID- 19745351
TI  - A knowledge model driven solution for web-based telemedicine applications.
AB  - Building knowledge-based telemedicine systems to deliver high quality services is
      still a challenge. The availability and capability of different human,
      communication and material resources play an important role in the telemedical
      task management process especially in emergency scenarios. In this paper we
      propose a knowledge model enabling intelligent, ubiquitous telemedicine tasks
      management. The objective of this model is to support the quality of telemedical
      services delivered by web-based telemedicine applications. The methodology is
      based on a telemedicine tasks ontology representing the concepts and their
      interrelations, and on a set of rules that shall be applied by a Reasoner for
      decision making. This architecture design shall optimize the messages exchange
      among the different actors in the telemedicine systems, consequently providing
      more rapid and reliable telemedicine assistance.

PMID- 19745352
TI  - Rural telemedicine networks using store-and-forward Voice-over-IP.
AB  - Store and forward Voice-over-IP is a suggested solution for supporting
      Telemedicine at rural health clinics in developing countries. Solutions described
      to date are designed to support communication by establishing point-to-point
      connectivity between two sites. In this paper we present an approach for creating
      scalable Telemedicine networks based on Delay Tolerant Networking. This holds
      potential for allowing Telemedicine networks to be created that can enable
      sharing of Teleconsultation and other medical information among a large number of
      locations in areas that cannot be served by existing solutions.

PMID- 19745353
TI  - An automated voice response system for anticoagulant therapy management.
AB  - The system described in this paper is aimed at improving the clinical workflow of
      post-stroke patients under oral anticoagulant therapy (OAT). The system helps
      both physicians and patients during the periodic control visits necessary to
      assess the anticoagulation status and the next therapeutic plan. Controls
      represent a burden for both patients, which after blood drawing must wait for the
      result, and for physicians, that, after assessing the therapy plan, must
      communicate it to patients, face-to-face or by telephone. A system is proposed,
      which embeds an algorithm for the patient-tailored calculation of the drug dosage
      and scheduling, and an automatic telephone dialogue for the communication of the
      therapy plan, once it has been validated or adjusted by the physician.

PMID- 19745354
TI  - Remote diagnosis of children dental problems based on non-invasive photographs -
      a valid proceeding?
AB  - Telemedicine models using commercially available technology have enabled high
      quality illness care in paediatric primary care settings and markedly improved
      access. This fact should be explored in Pediatric Dentistry, considering that
      dental problems are very common in children at pre-school age and it becomes
      important to screen them as early as possible in order to promote the appropriate
      treatment. In this sense, we aim to know how telemedicine, or more specifically,
      teledentistry, could help on this process, evaluating the validity of children
      dental problems remote diagnosis based on non-invasive photographs, using
      accessible and low-cost technologies. Three photographs were taken for each of 66
      children to be remotely analyzed by four dentists. Each dentist filled a web
      based questionnaire for each child. The same children had a traditional in-person
      dental consultation that is used as a gold standard in this study. The results
      show sensitivity between 94% and 100% and specificity between 52% and 100%. The
      positive predictive value was between 67% and 100% and the negative predictive
      value between 94% and 100%. These results suggest that remote diagnosis of
      children dental problems based on non-invasive photographs constitute a valid
      resource when we pretend to exclude referred children to a dentist for treatment
      of dental problems, but further studies should be carried out to increase the
      validity of this proceeding to referring children for the same treatment.

PMID- 19745355
TI  - KARDIONET: telecardiology based on GRID technology.
AB  - The telecardiological system Kardionet is being developed to support
      interventional cardiology. The main aim of the system is to collect specific and
      systemized patient data from the distant medical centers and to organize it in
      the best possible way to diagnose quickly and choose the medical treatment. It is
      the distributed GRID type system operating in shortest achievable time.
      Computational GRID solutions together with distributed archive data GRID support
      creation, implementation and operations of software using considerable
      computational power. Kardionet system devoted to cardiology purposes includes
      specially developed data bases for the multimodal data and metadata, including
      information on a patient and his/her medical examination results. As Kardionet
      uses modern technology and methods we expect it could have a considerable impact
      on telemedicine development in Poland. The presented telecardiological system can
      provide a number of important gains for the national health care system if it is
      implemented nationwide.

PMID- 19745356
TI  - Mobile phone-based teledermatologic compliance management - preliminary results
      of the TELECOMP study.
AB  - A mobile phone-based telemonitoring system for long-term psoriasis therapy is
      described, intended to increase patients' compliance by optimizing the patient
      physician communication. Patients themselves can acquire health parameters and
      take photos of their psoriasis lesions. The data are sent to a monitoring centre,
      where they are provided to the patients' physician who returns a feed-back
      message. The system is currently tested in a study with 20 patients. Preliminary
      results prove the feasibility and usabililty of such a system and indicate that
      it is useful for optimizing psoriasis-therapy.

PMID- 19745357
TI  - Measuring physical activity with sensors: a qualitative study.
AB  - Long term wearing of motion and heart rate sensors are essential aspects for
      longitudinal studies on physical activity measurement studies. We conducted a
      qualitative study with seven subjects in a total of 13 test sessions to identify
      usability and handling problems associated with Stayhealth RT3, Actigraph GT1M
      and Polar RS800 sensors. We found that battery life limitation is the most
      recurrent technical problem and long term wear of heart rate sensors produces
      discomfort and skin irritation.

PMID- 19745358
TI  - Representing sensor data using the HL7 CDA personal healthcare monitoring report
      draft.
AB  - The recently published implementation guide for personal healthcare monitoring
      report (PHMR) defines a new format to represent measurements. The aim of the
      presented prototypical implementation is to check the ability of the defined
      format to represent health-related sensor data using a commercially available
      multi-sensor-device's measurements. An extensible stylesheet language (XSL)
      stylesheet has been developed to transform measured data from the multi-sensor
      device to a valid PHMR document. The resulting documents are validated and
      evaluated using standard tools for processing extensible markup language (XML)
      documents. While there are multiple ways to represent data gathered by multi
      sensor devices in standard compliant CDA documents, the PHMR defines constraints
      based on the implementation guide for continuity of care documents (CCD) to
      support the development of new templates for sensor data and to minimize the
      variation between different implementations to enhance semantic interoperability.
      The PHMR implementation guide helps to define interoperable CDA conforming
      documents encoding data of health related sensors. In some parts the guide should
      be more restrictive to improve real-life interoperability.

PMID- 19745359
TI  - Monitoring driver's sleepiness on-board for preventing road accidents.
AB  - Driver sleepiness due to sleep deprivation is a causative factor of many road
      accidents. Reducing the extent of the sleepy driving problem by developing a
      countermeasure device that will monitor the sleepiness level of the driver is
      crucial to improve the safety of the roads. Among numerous physiological
      measurements, the electroencephalographic (EEG) signal seems to be the most
      sensitive to detect sleepiness. Previous studies in the field have found
      consistent alterations of EEG signal during sleepy driving, though they face
      methodological limitations. We present here preliminary results from a real
      driving experiment in which a more complete experimental setup was followed. The
      subjects were exposed to driving conditions twice: once after they had a normal
      sleep during the previous night, and once after they remained awake for at least
      24 hours prior to the experiment. Significant alterations were observed in the
      alpha and beta EEG frequencies bands between the two sessions.
      Electroopthalmographic (EOG) measurements revealed an increased number of eye
      blinking during the sleep-deprived session in comparison to the control
      condition. Both measurements can be used for the successful design of a
      sleepiness detection countermeasure device.

PMID- 19745360
TI  - Clinical implications of a quality assessment of transcutaneous CO2 monitoring in
      preterm infants in neonatal intensive care.
AB  - More than 1% of infants are born premature. Many of these children require
      special treatment because of immature organs and body functions. CO2 is an
      important parameter to monitor in order to avoid serious brain damage. Blood
      sampling of CO2 has several shortcomings and non-invasive transcutaneous CO2 is
      being investigated in order to assess its potential to contribute with the same
      type of information as blood CO2 measurements. The present study assesses the
      quality of transcutaneous CO2 data by comparing it to the "golden standard" blood
      CO2 data, in order to provide clinicians with a better understanding of the
      usefulness and limitations of transcutaneous CO2 data in neonatal care. The study
      shows that for low transcutaneous CO2 the error is relatively high and in most
      cases the true CO2, represented by the blood CO2, which can be regarded as the
      "gold standard", is higher than the measured transcutaneous CO2. The opposite is
      the case for high transcutaneous CO2. It is discussed how this is not due to any
      systematic error in the equipment, but due to the natural behaviour of noisy
      data.

PMID- 19745361
TI  - Drug information portal in Europe: information retrieval with multiple health
      terminologies.
AB  - The objective of this work is the creation of a bilingual (French/English) drug
      information portal (DIP), in a multi-terminological context. The development of
      the DIP was based on the CISMeF portal, which catalogues and indexes the most
      important and quality-controlled sources of institutional health information in
      French. DIP has created specific functionalities related to drug and used
      specific drugs terminologies and classifications: the ATC classification, the CAS
      numbers, the French codes CIS, and CIP, as well as trade names and the
      International Nonproprietary Names of the drugs. DIP is the result of
      collaboration between the CISMeF team and the VIDAL private Company, specialized
      in drug information. DIP is conceived to facilitate the user information
      retrieval using several health terminologies. In the framework of the drug field,
      using multi-terminological context, indexing drugs with the appropriate codes
      or/and terms revealed to be very important to have the appropriate information
      storage and retrieval.

PMID- 19745362
TI  - Is the "International Classification for Patient Safety" a classification?
AB  - The WHO has developed and is currently testing a classification for patient
      safety (ICPS). Analyzing the ICPS in the light of classificatory and ontology
      principles as well as international standards we conclude that its qualification
      as a classification or taxonomy is misleading. Acknowledging its merits as a
      standard reporting instrument for change management and process improvements we
      propose formal improvements.

PMID- 19745363
TI  - Ontological representation of adverse drug reactions using the Foundational Model
      of Anatomy.
AB  - In a previous work we proposed a categorial structure for the representation of
      adverse drug reactions consisting of 16 semantic categories and 20 relations. We
      present an implementation of this categorial structure in Protege based on four
      WHO-ART system organ classes: Gastro-intestinal system disorders, Liver and
      biliary system disorders, Central & peripheric nervous system disorders, and
      Psychiatric disorders. We compared classification according to anatomy using
      SNOMED CT within the PharmARTS tool and the FMA with the Pellet reasoner. This
      ontology contains 210 concepts for Gastroenterology, 66 concepts for Psychiatry
      and 85 concepts for Neurology. Classification of disorders located in the upper
      gastro intestinal tract was similar using both SNOMED CT and the FMA. This work
      is a first step towards the comparison of two models of anatomy within a common
      ontology of adverse drug reactions.

PMID- 19745364
TI  - Automatic construction of dictionaries, application to product characteristics
      indexing.
AB  - Summary of Product Characteristics (SPC) indexing enables to extract all the
      information needed to analyze a prescription and find some inappropriate
      medications. We evaluate a French Multi-Terminology Indexer tool (F-MTI) for SPC
      automatic indexing. This tool uses a dictionary containing the textual forms that
      are likely to appear in natural language text for the drug clinical particular
      terms contained in the Vidal thesaurus (TUV). We developed a method to
      automatically generate this dictionary. The evaluation showed a precision of
      52.9% and a recall of 46.2%. F-MTI will be integrated in a semi-automatic
      indexing tool.

PMID- 19745365
TI  - A knowledge management platform for documentation of case reports in
      pharmacovigilance.
AB  - Most countries have developed information systems to report drug adverse effects.
      However, as in other domains where systematic reviews are needed, there is little
      guidance on how systematic documentation of drug adverse effects should be
      performed. The objective of the VigiTermes project is to develop a platform to
      improve documentation of pharmacovigilance case reports for the pharmaceutical
      industry and regulatory authorities. In order to improve systematic reviews of
      adverse drug reactions, we developed a prototype that first reproduces and
      standardizes search strategies, then extracts information from the Medline
      abstracts which were retrieved and annotates them. The platform aims at providing
      transparent access and analysis tools to pharmacovigilance experts investigating
      relevance of safety signals related to drugs. The platform's architecture
      consists in the integration of two vendor tools ITM and Luxid and one academic
      web service for knowledge extraction from medical literature. Whereas a manual
      search performed by a pharmacovigilance expert retrieved 578 publications, the
      system proposed a list of 229 publications thus decreasing time required for
      review by 60%. Recall was 70% and additional developments are required in order
      to improve exhaustivity.

PMID- 19745366
TI  - Evaluation of an ontological resource for pharmacovigilance.
AB  - In this work, we present a methodology for evaluating an ontology designed in a
      previous study to describe adverse drug reactions. We evaluate it in term of its
      fitness for grouping cases in pharmacovigilance. We define as gold standard the
      Standardized MedDRA Queries (SMQs) developed manually to group terms representing
      similar medical conditions. We perform an automatic search in the ontology in
      order to retrieve concepts related to the medical conditions. An optimal query is
      built for each medical condition. The evaluation relies on the comparison between
      the terms in the SMQ and the terms subsumed by the query. The result is
      quantified by sensitivity and specificity. We applied this methodology for 24
      SMQs and we obtain a mean sensitivity of 0.82. This work allows validating the
      semantic resource and provides, in perspective, tools to maintain the ontology
      while the knowledge is evolving.

PMID- 19745367
TI  - Does computerised provider order entry reduce test turnaround times? A before-and
      after study at four hospitals.
AB  - Few multi-centre studies of the impact of computerised provider order entry
      (CPOE) systems on health care efficiency and effectiveness exist. Further,
      demonstrating a link between system use and improvements in patient outcomes is
      challenging. An often neglected step is to characterise the nature of the problem
      prior to CPOE introduction to ensure that the 'problem' being addressed has a
      demonstrated impact on the outcome of interest. We undertook a two-staged project
      to i) investigate the link between test turnaround time (TAT) and length of stay
      for emergency department patients prior to CPOE; ii) to measure the impact of
      CPOE on TAT in four Australian hospitals to examine the consistency of findings.
      We found TAT is a significant contributor to length of stay. All four hospitals
      experienced a significant reduction in TAT following CPOE. This study presents
      evidence that TAT is directly related to length of stay and that CPOE systems are
      effective at reducing TAT. These results add weight to the hypothesis that the
      introduction of CPOE may positively impact upon patient outcomes.

PMID- 19745368
TI  - Usability evaluation of a computerized physician order entry for medication
      ordering.
AB  - Despite CPOE (Computerized Physician Order Entry) systems' potential to enhance
      patient safety by reducing medication errors, recent studies have cast some
      doubts on their role in error reduction. CPOE systems with poorly designed
      interfaces have proven to cause users dissatisfaction and to introduce new kind
      of errors in the ordering process, suggesting a threat instead of an enhancement
      of patient safety. The main objective of this study is to identify usability
      problems related to a CPOE medication system's design and determining their
      severities. Two experts completed a cognitive walkthrough (CW) of an ordering
      task based on a clinical scenario for ordering the consolidation phase of
      chemotherapy for a leukemic patient. Fifty five usability problems were found and
      classified into eleven categories. CW identified cosmetic to catastrophic
      problems leading to inefficient use of the CPOE system and potentially resulting
      in users' confusion, longer ordering duration, and medication errors. The
      complexity of the CPOE design, its rigidness and lack of user guidance suggests
      the necessity to redesign the current user interface in order to match
      clinicians' ordering behaviors and to fully support them in the medication
      ordering process.

PMID- 19745369
TI  - An evolutionary approach to the representation of adverse events.
AB  - One way to detect, monitor and prevent adverse events with the help of
      Information Technology is by using ontologies capable of representing three
      levels of reality: what is the case, what is believed about reality, and what is
      represented. We report on how Basic Formal Ontology and Referent Tracking exhibit
      this capability and how they are used to develop an adverse event ontology and
      related data annotation scheme for the European ReMINE project.

PMID- 19745370
TI  - Human factors methods to support the experts' review of automatically detected
      adverse drug events.
AB  - The European project Patient Safety through Intelligent Procedures in Medication
      (PSIP) aims at semi-automatically identifying and preventing Adverse Drug Events
      (ADEs). Data mining of the structured hospital data bases provides a list of
      potential ADEs, along with their frequencies and probabilities. Once a set of
      ADEs has been detected by data mining techniques, it is necessary to have them
      validated by human experts. This paper presents the methods used to support the
      review by clinicians and pharmacologists of these automatically detected ADEs. We
      use think-aloud methods and portable labs to track and record the experts
      reasoning and their reviewing cognitive procedures. We present preliminary
      results obtained with this method, which allows identifying the key data and
      information used to characterize the ADEs.

PMID- 19745371
TI  - A framework for assessing adherence and persistence to long-term medication.
AB  - Poor adherence and persistence to long-term medication is a growing concern
      worldwide. Despite their importance, tools that facilitate the identification of
      patients who show poor adherence and persistence rates are limited. Herein we
      present a framework we have developed to assist in assessing adherence and
      persistence rates. We demonstrate the framework's features using production
      electronic medical record data from a general medical practice in the context of
      analysis of antihypertensive and antidepressant prescribing. The framework is
      flexible and extensible and has the potential to be used as a tool to improve the
      management of patients on long-term medication either to benchmark quality over a
      specified evaluation period or for the direct identification of specific patients
      that would benefit from immediate follow-up.

PMID- 19745372
TI  - Data-mining-based detection of adverse drug events.
AB  - Every year adverse drug events (ADEs) are known to be responsible for 98,000
      deaths in the USA. Classical methods rely on report statements, expert knowledge,
      and staff operated record review. One of our objectives, in the PSIP project
      framework, is to use data mining (e.g., decision trees) to electronically
      identify situations leading to risk of ADEs. 10,500 hospitalization records from
      Denmark and France were used. 500 rules were automatically obtained, which are
      currently being validated by experts. A decision support system to prevent ADEs
      is then to be developed. The article examines a decision tree and the rules in
      the field of vitamin K antagonists.

PMID- 19745373
TI  - Approaching harmonised medication information management through process and
      information modelling.
AB  - Medication information should be available in a correct content and format and
      where and when needed in medical care. In this paper process and information
      models are presented in order to identify the items, their relations, contents,
      sources and use contexts of medication information. The motivation for this study
      has been to develop a harmonized information model for medication information to
      overcome current problems and pitfalls in medication information management and
      information accessibility.

PMID- 19745374
TI  - Feasibility study of a web application for self-report of anticancer treatment
      toxicities.
AB  - Collection of collateral effects related to toxicities suffered by patients being
      exposed to anticancer treatments is of crucial importance in clinical practice
      but also in oncological research. The present paper describes a web application
      called PaTOS for self-report of anticancer therapy toxicities, and its evaluation
      in a preliminary interface analysis and then in a feasibility study.

PMID- 19745375
TI  - Automatic medical knowledge acquisition using question-answering.
AB  - We aim at proposing a rule generation approach to automatically acquire
      structured rules that can be used in decision support systems for drug
      prescription. We apply a question-answering engine to answer specific information
      requests. The rule generation is seen as an equation problem, where the factors
      are known items of the rule (e.g., an infectious disease, caused by a given
      bacteria) and solutions are answered by the engine (e.g., some antibiotics). A
      top precision of 0.64 is reported, which means, for about two third of the
      knowledge rules of the benchmark, one of the recommended antibiotic was
      automatically acquired by the rule generation method. These results suggest that
      a significant fraction of the medical knowledge can be obtained by such an
      automatic text mining approach.

PMID- 19745376
TI  - Mining administrative and clinical diabetes data with temporal association rules.
AB  - The Regional Healthcare Agency (ASL) of Pavia has been collecting and maintaining
      a central data repository which stores both administrative and clinical
      healthcare data about the population of Pavia area. The analysis of such
      integrated databases could greatly help to extract useful information for the
      assessment of health care delivery process. In this paper we focus our attention
      on the care delivery flow of Diabetes Mellitus, and we show the application of an
      algorithm for the extraction of Temporal Association Rules on sequences of hybrid
      events. This method allows to properly exploit the integration of different
      healthcare information sources, and can be used to evaluate the pertinence of the
      care delivery flow for specific pathologies, in order to reassess or refine the
      inappropriate practices which lead to unsatisfactory outcomes.

PMID- 19745377
TI  - Knowledge discovery about quality of life changes of spinal cord injury patients:
      clustering based on rules by states.
AB  - In this paper, an integral Knowledge Discovery Methodology, named Clustering
      based on rules by States, which incorporates artificial intelligence (AI) and
      statistical methods as well as interpretation-oriented tools, is used for
      extracting knowledge patterns about the evolution over time of the Quality of
      Life (QoL) of patients with Spinal Cord Injury. The methodology incorporates the
      interaction with experts as a crucial element with the clustering methodology to
      guarantee usefulness of the results. Four typical patterns are discovered by
      taking into account prior expert knowledge. Several hypotheses are elaborated
      about the reasons for psychological distress or decreases in QoL of patients over
      time. The knowledge discovery from data (KDD) approach turns out, once again, to
      be a suitable formal framework for handling multidimensional complexity of the
      health domains.

PMID- 19745378
TI  - A searchable patient record database for decision support.
AB  - We describe a searchable patient record database for decision support. It
      contains medical histories of real but pseudonymous patients with patterns of
      diagnosis, chosen treatment, and outcome. To be searchable, the patterns contain
      a feature vector (for similarity search by calculating distances) and a globally
      unique "pattern name" which identifies the kind of data which are represented by
      the feature vector. Patterns with the same pattern name are directly comparable;
      they represent the same kind of data. For pattern selection the database provides
      a growing well-structured list of initial diagnoses with associated input masks.
      PROCEDURE: The doctor can assume that the database contains patients similar to
      the current patient if he finds his initial diagnosis in the list. Clicking on it
      opens an associated input mask which requests specific further data for finer
      differentiation. After input a searchable pattern group is built from the
      provided data, and used to search for histories of patients with similar fine
      diagnostics, and for the most successful treatment decisions at these patients.
      This information can be very valuable for deciding the treatment of the current
      patient. Because the database can collect patient histories from all countries,
      in the long run this could open access to a wealth of experience which by far
      exceeds the capacity of a today's doctor.

PMID- 19745379
TI  - Knowledge discovery in neuroinformatics.
AB  - Traditionally, the process of turning data into biomedical knowledge has involved
      "manual" meta-analyses of results reported in journals. Since the amount of
      scientific data produced in neuroscience today increases dramatically, the
      resultant expansion of the medical databases has created a significant potential
      for the design of new data modeling and information retrieval tools and services
      that enable faster data processing, analysis and dissemination among a highly
      interdisciplinary community of researchers.

PMID- 19745380
TI  - Dynamic data analysis and data mining for prediction of clinical stability.
AB  - This work studies the impact of using dynamic information as features in a
      machine learning algorithm for the prediction task of classifying critically ill
      patients in two classes according to the time they need to reach a stable state
      after coronary bypass surgery: less or more than nine hours. On the basis of five
      physiological variables different dynamic features were extracted. These sets of
      features served subsequently as inputs for a Gaussian process and the prediction
      results were compared with the case where only admission data was used for the
      classification. The dynamic features, especially the cepstral coefficients (aROC:
      0.749, Brier score: 0.206), resulted in higher performances when compared to
      static admission data (aROC: 0.547, Brier score: 0.247). In all cases, the
      Gaussian process classifier outperformed logistic regression.

PMID- 19745381
TI  - A methodology for the extraction of quantitative risk indexes from medical
      injuries compensation claims.
AB  - The prevention of adverse events and medical injuries due to malpractice or
      suboptimal delivery of health care services is one of the major concerns of
      citizens and Health Care Organizations. One way to understand adverse events is
      to analyze the compensation requests for medical injuries that are claimed to
      hospital or health care services. In this paper we describe the results obtained
      by applying a probabilistic model, called the actuarial model, to analyze 317
      cases of injuries with compensation requests collected from 1999 to the first
      semester of 2007 by the Azienda Ospedaliera (A.O.) of Lodi, in the Northern part
      of Italy. The approach, adapted from operational and financial risk management,
      proved to be useful to understand the risk structure in terms of frequency,
      severity, expected and unexpected loss related to adverse events.

PMID- 19745382
TI  - Comparison of Bayesian network and decision tree methods for predicting access to
      the renal transplant waiting list.
AB  - The study compares the effectiveness of Bayesian networks versus Decision Trees
      for predicting access to renal transplant waiting list in a French healthcare
      network. The data set consisted in 809 patients starting renal replacement
      therapy. The data were randomly divided into a training set (90%) and a
      validation set (10%). Bayesian network and CART decision tree were built on the
      training set. Their predictive performances were compared on the validation set.
      The age variable was found to be the most important factor in both models. Both
      models were highly sensitive and specific: sensitivity 90.0% (95%CI: 76.8-100),
      specificity 96.7% (95%CI: 92.2-100). Moreover, the models were complementary
      since the Bayesian network provided a global view of the variables' associations
      while the decision tree was more easily interpretable by physicians. These
      approaches provide insights on the current care process. This knowledge could be
      used for optimizing the healthcare process.

PMID- 19745383
TI  - Developing a theoretical model of clinician information usage propensity.
AB  - Based on qualitative research, we developed the theoretical construct "clinician
      information usage propensity" as a hypothetical indicator of attitudes and
      behaviour towards clinical information and systems. We devised a survey to
      validate the construct and had 146 responses. Principal components analysis
      extracted four factors accounting for 47.2% of the variance: beliefs about
      clinical judgement, beliefs about information quality, cultural resistance and
      cognitive approach. The components were reasonably consistent with the model but
      two factors (beliefs about information quality, cognitive approach) had low
      reliability (alpha<0.6). Cultural resistance was the main factor and correlated
      with gender, grade and age group. Female clinicians showed significantly higher
      cultural resistance and preference for narrative; hospital doctors generally had
      higher cultural resistance than general practitioners. As only 47.2% of the
      variance was explained, further work is needed to refine the instrument to remove
      redundancy, improve sensitivity on the identified components and allow the
      construct to be explored as a form of technology adoption model. We posit that
      beliefs about clinical judgement merit further attention in medical informatics
      research.

PMID- 19745384
TI  - Using artificial neural networks to predict potential complications during trauma
      patients' hospitalization period.
AB  - Complications during treatment of seriously injured trauma patients cause an
      increase in mortality rates, and increased treatment costs, including bed
      occupancy. Current methods treat those at risk, and include numbers of false
      positives. By finding a method to predict those at risk of the three most common
      recorded Trauma Registry complications, considerable savings in mortality and
      treatment costs could arise. Artificial Neural Networks (ANN) work well with
      classification problems using feed-forward/back propagation methodology. Using
      the National Trauma Data Bank (V6.2) data files, Tiberius Software created the
      ANN models. Best models were identified by their Gini co-efficient, ability to
      predict the complication outcome selected, and their Root Mean Squared Error
      (RMSE) scores. The model ensemble for the three major complications recorded in
      the registry were determined, variables ranked and model accuracy recorded. The
      basic ANN is fairly accurate for those likely to contract Acute Respiratory
      Disease Syndrome (ARDS) though with a high rate of false positives. The ANN
      ability to predict Ventilator Associated Pneumonia (VAP) is less effective,
      though better at producing fewer false positives. Predicting Urinary Tract
      Infections (UTI) cases is not good enough using these input variables. Both VAP
      and UTI relate to those aged over 55 years, while ARDS related more to those
      under 16 years. The models need improving.

PMID- 19745385
TI  - Optimized detection of tar content in the manufacturing process using adaptive
      neuro-fuzzy inference systems.
AB  - The purpose of this study is to model and optimize the detection of tar in
      cigarettes during the manufacturing process and show that low yield cigarettes
      contain similar levels of nicotine as compared to high yield cigarettes while B
      (Benzene), T(toluene) and X (xylene) (BTX) levels increase with increasing tar
      yields. A neuro-fuzzy system which comprises a fuzzy inference structure is used
      to model such a system. Given a training set of samples, the Adaptive Neuro-Fuzzy
      Inference System (ANFIS) classifiers learned how to differentiate a new case in
      the domain. The ANFIS classifiers were used to detect the tar in smoke condensate
      when five basic features defining cigarette classes indications were used as
      inputs. A classical method by High Performance Liquid Chromatography (HPLC) is
      also introduced to solve this problem. At last the performances of these two
      methods are compared.

PMID- 19745386
TI  - The effect of removing the force feedback during the quiet stance.
AB  - The human postural control system is complex and it combines information from
      different sources. The most important information comes from vestibular, visual
      and proprioceptive senses. We studied the effects of removing the visual and
      proprioceptive information simultaneously. The force feedback from the ground was
      removed with vibrators attached on the musculus soleus of both calves. By using
      features of force platform signals, when the vibrators were on, the lengths of
      the swaying paths were four times the lengths when the vibrators were off. Our
      results show that it is possible to separate the effects of the visual and
      proprioceptive senses from that of vestibular sense, which is very useful for
      investigations of balance problems in otoneurology. This supports our future aim
      to classify between healthy subjects and different otoneurological patients with
      signal analysis and pattern recognition methods to be used for force platform
      signals.

PMID- 19745387
TI  - Object-oriented integrated approach for the design of scalable ECG systems.
AB  - The paper presents the implementation of Object-Oriented (OO) integrated
      approaches to the design of scalable Electro-Cardio-Graph (ECG) Systems. The
      purpose of this methodology is to preserve real-world structure and relations
      with the aim to minimize the information loss during the process of modeling,
      especially for Real-Time (RT) systems. We report on a case study of the design
      that uses the integration of OO and RT methods and the Unified Modeling Language
      (UML) standard notation. OO methods identify objects in the real-world domain and
      use them as fundamental building blocks for the software system. The gained
      experience based on the strongly defined semantics of the object model is
      discussed and related problems are analyzed.

PMID- 19745388
TI  - Modelling clinical guidelines and protocols for the prevention of risks against
      patient safety.
AB  - The detection and prevention of Risks Against Patient Safety (RAPS) are ever
      increasing issues in health care. One aspect of the many measures taken against
      RAPS is the comparison of the actual care practice against descriptions of best
      practice given in clinical guidelines and protocols (CGPs). In order to perform
      such comparisons automatically, CGPs need to be modelled in a computer-executable
      form. In addition, the execution of the CGP model must be integrated with the
      care process at the site of application, and with risk-assessment tools used by
      the hospital's risk manager to explore what-if scenarios. In this paper, we
      describe the modelling and execution of CGPs in Asbru within the EU project
      Remine, which develops a high-performance platform for the prediction, detection
      and monitoring of RAPS.

PMID- 19745389
TI  - Computerization framework for clinical practice guidelines by extending the XML
      guidelines element model (GEM).
AB  - Contextually sensitive and semantically related evidence-based knowledge play an
      important role in decision-making. Clinical practice guidelines (CPG) are being
      developed to provide a rich source of up-to-date knowledge of evidence-based best
      clinical practices. Such knowledge assists healthcare practitioner in specific
      clinical circumstances at their decision-points. In many studies, it was shown
      that the effectiveness of CPG could be improved with their computerization. In
      this paper, we present our CPG-knowledge computerization framework that has been
      developed and implemented along the lines of knowledge management approaches.
      This framework adds context, semantics and related meta-information to the CPGs
      knowledge content using an extended-knowledge component ontology and UMLS. It
      also transforms them into a set of structured 'extended-knowledge components'.
      These extended-knowledge components constitute a 'CPG knowledge base', which is
      used for providing assistance at point of care.

PMID- 19745390
TI  - Computerizing clinical pathways: ontology-based modeling and execution.
AB  - Clinical Pathways (CP) stipulate an evidence-based patient care workflow for a
      specific disease within a localized setting. We present an ontology-based
      approach for computerizing CP so that they can be executed at the point-of-care.
      We present our CP modeling approach that features the integration of multiple
      localized CP to realize a unified disease-specific CP. The execution of the
      ontological CP model is achieved by our property abstraction method that assigns
      functional behaviors to existing semantic properties to facilitate their
      execution. Using our methods we have developed a prostate cancer management
      system.

PMID- 19745391
TI  - A formal logical framework for Cadiag-2.
AB  - Cadiag-2-where "Cadiag" stands for "computer-assisted diagnosis"- is an expert
      system based on fuzzy logic assisting in the differential diagnosis in internal
      medicine. With its aid, it is possible to derive from possibly vague information
      about a patient's symptoms, signs, laboratory test results, and clinical findings
      conjectures about present diseases. In this paper, we provide a mathematical
      formalization of the inferential mechanism of Cadiag-2. The aim is to have a
      formal logical calculus at hand which corresponds to the mode of operation of
      Cadiag-2 and which is among others needed to perform consistency checking of
      Cadiag-2's medical knowledge base.

PMID- 19745392
TI  - Representing a chemotherapy guideline using openEHR and rules.
AB  - Computerized guidelines can provide decision support and facilitate the use of
      clinical guidelines. Several computerized guideline representation models (GRMs)
      exist but the poor interoperability between the guideline systems and the
      Electronic Health Record (EHR) systems limits their clinical usefulness. In this
      study we analyzed the clinical use of a published lymphoma chemotherapy
      guideline. We found that existing GRMs have limitations that can make it
      difficult to meet the clinical requirements. We hypothesized that guidelines
      could be represented as data and logic using openEHR archetypes, templates and
      rules. The design was tested by implementing the lymphoma guideline. We conclude
      that using the openEHR models and rules to represent chemotherapy guidelines is
      feasible and confers several advantages both from a clinical and from an
      informatics perspective.

PMID- 19745393
TI  - The use of SNOMED CT for representing concepts used in preoperative guidelines.
AB  - The use of guidelines to improve quality of care depends on presenting them in a
      standard machine-interpretable form and using common terms in guidelines as well
      as in patient records. In this study, the use of SNOMED CT for representing
      concepts used in preoperative assessment guidelines was evaluated. Terms used in
      six of these guidelines were mapped to this terminology. Mappings were presented
      based on three scores: no match, partial match, and complete match. As eleven of
      the terms were repeatedly used in different guidelines, we analyzed the results
      based on "token" and "type" coverage. Of 133 extracted terms from guidelines, 107
      terms should be covered by SNOMED CT of which 87% was completely represented by
      this terminology. Our study showed that SNOMED CT content should be extended
      before preoperative assessment guidelines can be completely automated.

PMID- 19745394
TI  - Embedding oncologic protocols into the provision of care: the Oncocure project.
AB  - A computerized Decision Support System (CDSS) can improve the adherence of the
      clinicians to clinical guidelines and protocols. Integrating it within the
      clinical workflow can reduce the workload of the physicians, and improve the
      acceptance of the system. The building of a prescriptive CDSS and its integration
      with a legacy cancer patient management system is the aim of the Oncocure
      project, which implements the existing protocol for the medical treatment of
      breast cancer in the Asbru language, and interfaces the Asbru interpreter with
      the Electronic Patient Record (EPR) in use in an oncologic unit. Our work is not
      constrained to a specific domain or EPR implementation, but can be generalized to
      other fields of medicine and patient management systems. When implemented, our
      CDSS is expected to reduce the cost of care while improving the adherence to the
      guideline and the quality of the documentation.

PMID- 19745395
TI  - Using knowledge modelling to measure how clinical practice could actually be
      evidence-based: a preliminary analysis with arterial hypertension management.
AB  - ASTI is a guideline-based decision support system to be used in primary care. We
      analyzed the knowledge modelling carried out in the development of ASTI knowledge
      base (KB) from French clinical practice guidelines (CPGs) on arterial
      hypertension management to evaluate the evidence status of therapeutic
      propositions issued by the system. We defined three status: "evidence-based" (EB)
      when propositions are graded A, B, or C, "consensus-based" (CB) when propositions
      are explicitly mentioned in CPGs but supported by professional agreement (grade
      D), and "non-supported" (NS) when propositions are expert-based and provided by a
      domain specialist. We compared the distributions of evidence status on the 44,571
      theoretical patient profiles extracted from ASTI KB, and on a data set of 435
      actual hypertensive patients. Only 8.3% of actual patients, managed by 0.5% of
      the KB, have an EB profile and 46.9% of patients, managed by 12.6% of the KB,
      have a CB profile. Thus, there is no CPG recommendation for nearly half of the
      patients (44.8% have a NS profile).

PMID- 19745396
TI  - Computer-based physician order entry: implementation of clinical pathways.
AB  - Computer-based physician order entry (CPOE) is a key feature of electronic health
      record systems. A fully-featured CPOE system, capable of dealing with drug
      prescription, but also with all the other aspects of patients care, can be used
      to implement standardized clinical pathways. This classic design can be improved
      upon by using a workflow engine to drive and bring together the different tasks
      incorporated in a pathway, including clinical documentation.

PMID- 19745397
TI  - Clinician reports of the impact of electronic ordering on an emergency
      department.
AB  - The importance of health informatics evaluations adopting a pluralist approach
      which considers the technical as well as the organizational and social aspects of
      system implementation has been espoused by many researchers. Kaplan's 4Cs
      evaluation framework presents a lens through which evaluations of clinical
      systems can be assessed, with a focus on communication, care, control and
      context. Our aim was to investigate the effects of Computerized Provider Order
      Entry (CPOE) on Emergency Department (ED) work, communication practices and
      patient care using this framework as a means to orient the study. A qualitative
      study using interviews and focus groups was undertaken in an Australian 640-bed
      ED after the introduction of CPOE. Systematic concurrent analysis revealed five
      themes: i) Expectations; ii) Changes in responsibility; iii) Monitoring of the
      test order process; iv) System usability; and v) System requirements. CPOE
      systems in EDs present specific challenges which differ from other hospital
      departments. Due to the critical nature of clinical work in this setting a poor
      fit between CPOE and ED work may result in serious incidents.

PMID- 19745398
TI  - Empowering clinicians by eHealth technologies in decision-making tasks.
AB  - We present three types of eHealth applications that can enhance quality of
      clinical decision-making. Formalized electronic medical guidelines are bringing
      medical knowledge close to clinicians. eHealth tools for evaluation knowledge and
      competency in a given clinical decision-making problem are demonstrated by
      systems ExaMe and TECOM. The TECOM system supports training of clinical
      competence in a given decision-making problems using real clinical cases. The
      TECOM system estimates the decision-maker abilities using a coefficient of
      prediction or a classical error rate. Transfer of data and knowledge important
      for clinical decision-making without language barriers is demonstrated on
      features of the European Journal for Biomedical Informatics.

PMID- 19745399
TI  - Medintel: decision support for general practitioners: a case study.
AB  - Short consultations and a large and growing amount of available medical
      information make searching for suitable information difficult for general
      practitioners. Thus information is often not searched for or not found,
      diminishing the quality of care. We propose a system that offers decision support
      by combining medical information sources with data from the electronic patient
      record. A first evaluation shows that a system like Medintel can be a useful
      supportive tool and can increase the quality of care provided by general
      practitioners.

PMID- 19745400
TI  - Modelling and enforcing privacy for medical data disclosure across Europe.
AB  - The harmonization of data protection legislation in Europe has been theoretically
      achieved by means of the EU directive on data protection. In practice the
      harmonization is not absolute and conflicts and inconsistencies continue to exist
      in the way Member States are implementing the directive. The integration of
      different European medical systems by means of grid technologies will continue to
      be challenging if technology does not intervene to enhance interoperability
      between national regulatory frameworks on data protection. In this paper we
      present an approach to automate privacy requirements for the sharing of patient
      data across Europe on a healthgrid domain and ensure its enforcement internally
      and within external domains where the data might travel. This approach is based
      on the semantic modelling of privacy obligations that are of legal, ethical or
      cultural nature. These requirements are for the sharing of personal data between
      different European Member States. Our model reflects both similarities and
      conflicts, if any, between the different Member States. This allows us to reason
      on the safeguards a data controller should ask from an organization belonging to
      another Member State before disclosing medical data to them. The system will also
      generate the relevant set of policies to be enforced at the process level of the
      grid to ensure privacy compliance before allowing access to the data.

PMID- 19745401
TI  - Centralised versus decentralised management of patients' medical records.
AB  - For more than 20 years, many countries have been trying to set up a standardised
      medical record at the regional or at the national level. Most of them have not
      reached this goal, essentially due to two main difficulties related to patient
      identification and medical records standardisation. Moreover, the issues raised
      by the centralisation of all gathered medical data have to be tackled
      particularly in terms of security and privacy. We discuss here the interest of a
      non-centralised management of medical records which would require a specific
      procedure that gives to the patient access to his/her distributed medical data,
      wherever he/she is located.

PMID- 19745402
TI  - Emergency access to protected health records.
AB  - Digital Rights Management (DRM) schemes are receiving increased attention in the
      healthcare domain for the protection of sensitive health records as they offer
      security against insider attacks and advance protection features such as usage
      control. However, to be accepted by health care providers, a DRM solution has to
      fulfill specific healthcare requirements including emergency access. In this
      paper, we propose such DRM solution that can be deployed in highly distributed
      environments of electronic or personal health record infrastructures.

PMID- 19745403
TI  - Threats to information security of real-time disease surveillance systems.
AB  - This paper presents the main results from a qualitative risk assessment of
      information security aspects for a new real-time disease surveillance approach in
      general, and for the Snow surveillance system in particular. All possible
      security threats and acceptable solutions, and the implications these solutions
      had to the design of the system, were discussed. Approximately 30 threats were
      identified. None of these got an unacceptable high risk level originally, but two
      got medium risk level, of which one was concluded to be unacceptable after
      further investigation. Of the remaining low risk threats, some have severe
      consequence, thus requiring particular assessment. Since it is very important to
      identify and solve all security threats before real-time solutions can be used in
      a wide scale, additional investigations are needed.

PMID- 19745404
TI  - Visualizing patient trajectories on wall-mounted boards - information security
      challenges.
AB  - Since operating room departments are among the costliest resources at a hospital,
      much attention is devoted to maximize their utilization. Operating room
      activities are however notoriously hard to plan in advance. This has to do with
      the unpredictable, problem-solving nature of the work and that the work is
      carried out by a multidisciplinary team of health personnel, members of which
      also have commitments outside the operating room department. We assume that
      operating room teams have the capacity to coordinate themselves and that
      coordination might be facilitated by visualizing relevant information on wall
      mounted boards. To characterize clinical situations that require coordination and
      re-planning of the teams' work, we have developed a realistic scenario. We
      analyse and discuss the information security challenges that follow from
      displaying information on the whereabouts of other teams, actors and patients on
      wall-mounted boards in the operating rooms. Information security threats could be
      mitigated by de-identification techniques. Information demands could thereby be
      met without sacrificing the privacy of those whose information is displayed.

PMID- 19745405
TI  - Requirements for radio frequency identification in healthcare.
AB  - Radio frequency identification (RFID) is a growing technology among different
      industries. As a technology, it has been used since the Second World War, but
      just in the last decade, the information technology (IT) community and healthcare
      have been taking more action on studying and developing the technology. In this
      paper, we represent the general requirements that healthcare sets for the RFID
      technology. The paper is a part of the research project MaISSI (Managing IT
      Services and Service Implementation) where our aim is to implement an automated
      identification system (AIMC) for our case hospital's medication care. The AIMC
      uses the RFID technology for patient identification and the bar code technology
      for medication identification. The system will automate the identification
      processes during medication administration, reduce medication errors and increase
      the patient safety.

PMID- 19745406
TI  - Authentication and encryption in the Snow disease surveillance network.
AB  - The paper presents how authentication and encryption is implemented in the Snow
      disease surveillance network. Requirements for the authentication mechanism were
      collected from General Practitioners (GPs). The identity of each Snow user is
      preserved across health institutions allowing GPs to move freely between health
      institutions and use the system independent of location. This ability is combined
      with close to zero user account administration within the participating
      institutions. The system provides global user certificate revocation and end-to
      end encryption.

PMID- 19745407
TI  - Securing a web-based teleradiology platform according to German law and "best
      practices".
AB  - The Medical Data and Picture Exchange platform (MDPE), as a teleradiology system,
      facilitates the exchange of digital medical imaging data among authorized users.
      It features extensive support of the DICOM standard including networking
      functions. Since MDPE is designed as a web service, security and confidentiality
      of data and communication pose an outstanding challenge. To comply with demands
      of German laws and authorities, a generic data security concept considered as
      "best practice" in German health telematics was adapted to the specific demands
      of MDPE. The concept features strict logical and physical separation of
      diagnostic and identity data and thus an all-encompassing pseudonymization
      throughout the system. Hence, data may only be merged at authorized clients.
      MDPE's solution of merging data from separate sources within a web browser avoids
      technically questionable techniques such as deliberate cross-site scripting.
      Instead, data is merged dynamically by JavaScriptlets running in the user's
      browser. These scriptlets are provided by one server, while content and method
      calls are generated by another server. Additionally, MDPE uses encrypted
      temporary IDs for communication and merging of data.

PMID- 19745408
TI  - Testing tactics to localize de-identification.
AB  - Recent renewed interest in de-identification (also known as "anonymisation") has
      led to the development of a series of systems in the United States with very good
      performance on challenge test sets. De-identification needs however to be tuned
      to the local documents and their specificities. We address here two issues raised
      in this context. First, tuning is generally performed by language engineers who
      should not have to work on identified text. We therefore perform a first gross de
      identification step in the hospital. Second, to set up a de-identification system
      for new documents in a language different from English, here French patient
      reports, we tested two methods: the first attempts to adapt an existing US de
      identifier for English, the second re-develops a new system which applies the
      same methods. The first method involved localizing patterns designed for English,
      which proved cumbersome and did not quickly obtain good performance. With a
      similar effort, the latter method obtained much better results. Evaluated on a
      set of 23 randomly selected texts from a corpus of 21,749 clinical texts, it
      obtained 83% recall and 92% precision.

PMID- 19745409
TI  - Computer-mediated mobile messaging as collaboration support for nurses.
AB  - Collaboration in hospitals is coordinated mainly by communication, which
      currently happens by face-to-face meetings, phone calls, pagers, notes and the
      electronic patient record. These habits raise problems e.g., delayed
      notifications and unnecessary interruptions. Dealing with these problems could
      save time and improve the care. Therefore we designed and prototyped a mobile
      messaging solution based on two specific scenarios coming from observations at a
      cardiology department of a Norwegian hospital. The main focus was on supporting
      the work of nurses. One prototype supported patient management while another one
      dealt with messages related to medication planning. The evaluation of the
      prototypes suggested that messaging-based collaboration support is worth to
      explore and also gave ideas for improvement.

PMID- 19745410
TI  - Collection and sharing of information on patient safety education and training in
      Europe.
AB  - The European Union Network for Patient Safety (EUNetPaS) is a project funded and
      supported by the European Commission within the 2007 Public Health Programme and
      aims to encourage and enhance the collaboration of participating EU countries in
      the field of Patient Safety. One of its major objectives is to promote Patient
      Safety (PS) education and training in Member States, through building a platform
      for mutual exchange of experience and knowledge on methods of planning and
      implementing sustainable learning activities. Towards this direction, a
      methodology has been applied, based on a three axes schema, which describes the
      roles, the awareness level and the competences of the PS Education and Training
      Activities. Based on this scheme, a questionnaire has been developed and
      distributed across EU organizations though National Contact Points, as a tool for
      information collection. Looking to the above structure, a web-based resource has
      been developed aiming to facilitate the information collection and sharing, in a
      truly networking environment.

PMID- 19745411
TI  - Patient education on safety and privacy.
AB  - The individual's right to determine if, when and how data about them will be
      collected, stored, used and shared with others is called the right to privacy.
      The problem of data collection and sharing arises daily among health services.
      Among medical staff, there are numerous message flows, including the medical
      records of patients and other patient's personal data. These data are often
      completely unprotected and available to anyone who knows where it is.
      Unfortunately, the same data might not be available for patients, despite the
      fact that each individual has the right to view their own medical record and
      despite the fact that many other persons connected directly or indirectly to the
      patient has this access without limitations. In the paper, we will not
      concentrate on actions that medical staff has to perform nor on the knowledge
      that they have to have in order to protect a patient's personal data and enable a
      patient's access to their own data, but we will concentrate on the problem of
      educating patients about their rights and duties with regard to safety and
      privacy. Our educational suggestions will be given on the basis of corresponding
      Slovenian legislation and guidelines for medical staff regarding the protection
      of personal data.

PMID- 19745412
TI  - European efforts in nanoinformatics research applied to nanomedicine.
AB  - Nanomedicine and nanoinformatics are emerging disciplines with substantial
      challenges ahead. For instance, nanomedicine involves complex and massive data
      analysis. Nanoinformatics could expand previous experiences in Biomedical
      Informatics with new features required to study different scientific biological
      and physical characteristics at a different level of complexity. ACTION-Grid is a
      project, funded by the European Commission, which aims to the creation of a
      collaborative environment in biomedical and nanomedical research among countries
      in Europe, Western Balkans, Latin America and North Africa. In this paper, we
      briefly review the concepts of nanomedicine and nanoinformatics and then we
      describe the activities of some of the ACTION-Grid consortium members considering
      those initiatives related to nanomedicine.

PMID- 19745413
TI  - Single nucleotide polymorphisms and health behaviours related to obesity -
      trawling the evidence in the prospect of personalised prevention.
AB  - Efforts aimed at primary and secondary prevention of cardiovascular diseases, the
      major killer of contemporary adult populations, largely rely on modification of
      risk behaviours related to smoking, physical activity, dietary intake, and
      alcohol consumption, and also control of obesity and hypertension, the interim
      risk states between health and disease. We propose that the extent to which the
      gene x 'obesogenic' environment interaction depends on associations between
      particular single nucleotide polymorphisms (SNPs) and behavioural risk factors
      for overweight or obesity determines opportunities for novel, personalised
      preventive interventions. We systematically searched for SNPs that might be of
      interest for this postulate, and we present various SNPs that have been shown to
      be associated with overweight or obesity and behavioural risk factors for
      developing these traits, and thus hold promise for future design of personalised
      preventive interventions.

PMID- 19745414
TI  - GeneMining: identification, visualization, and interpretation of brain ageing
      signatures.
AB  - Transcriptomic technologies are promising tools for identifying new genes
      involved in cerebral ageing or in neurodegenerative diseases such as Alzheimer's
      disease. These technologies produce massive biological data, which so far are
      extremely difficult to exploit. In this context, we propose GeneMining, a
      multidisciplinary methodology, which aims at developing new strategies to analyse
      such data, and to design interactive tools to help biologists to identify,
      visualize and interpret brain ageing signatures. In order to address the specific
      problem of brain ageing signatures discovery, we combine and apply existing tools
      with emphasis to a new efficient data mining method based on sequential patterns.

PMID- 19745415
TI  - Machine learning analysis of proteomics data for early diagnosis.
AB  - Ovarian cancer (OC) can usually clinically be diagnosed only at the late stages
      of the disease. We show that the combination of the biomarker antigen CA125 with
      proteomic mass spectra data and applying newly developed machine learning
      algorithms, may establish a diagnosis of OC very early.

PMID- 19745416
TI  - Cadiag-2 and fuzzy probability logics.
AB  - We briefly describe the medical expert system Cadiag-2, developed to support the
      differential diagnostic process in internal medicine. We propose a propositional
      logic called fuzzy probability logic as a possible formalization of Cadiag-2 and
      indicate the way of transferring Cadiag-2's methodology into this framework.

PMID- 19745417
TI  - Equity of accessibility to dialysis facilities.
AB  - Patients' end-stage renal disease (ESRD) characteristics are changing. Improving
      the quality of care requires a steady adaptation of treatment modalities together
      with equity of access to dialysis facilities. We explored the ability of the
      health system to cope with the demand of ESRD care. An analysis of a 5-year
      follow-up cohort of ESRD patients in the Limousin region, France, was performed.
      Data were entered in the Multi-Source Information System of the Renal
      Epidemiology and Information Network (REIN). The participation rate of centres
      was complete. We analysed patient characteristics, therapeutic options and
      driving time to reach dialysis facilities. We investigated geographic
      accessibility by defining areas within 45 minutes from dialysis units. We
      constructed scenarios to assess the impact of health care reorganization. In
      centre haemodialysis units represented 73% of treatment modalities. One quarter
      of patients lived at more than 45 minutes of their dialysis unit. Based on a
      scenario of creating an additional In-centre unit, the number of patients living
      far from their centre would decrease by 31%. This study emphasizes important
      issues related to ESRD epidemiology, comorbidity and health care planning. It
      stimulates the development of new scenarios allowing the assessment of equity in
      accessing health care facilities.

PMID- 19745418
TI  - Assessing importance of dietary data in anticoagulation treatment.
AB  - This paper describes the outcome of including information on dietary intake in
      the attempt to predict International Normalized Ratio (INR) values. An already
      published model has been extended and is now tested with the additional dietary
      data and without it. When predicting INR values seven days into the future, the
      new proposed model outperforms the existing one. It is concluded that adding
      information on dietary intake improves the accuracy of INR predictions.

PMID- 19745419
TI  - An automated system for processing electrodermal activity.
AB  - A new approach is presented in this paper for the display and processing of
      electrodermal activity. It offers a fully automated interface for the pre
      processing and scoring individual skin conductance responses (SCRs). The
      application supports parallel processing by means of multiple threads. Batch
      processing is also available. The XML format is used to describe the derived
      features. The system is employed to analyze emotion-related data.

PMID- 19745420
TI  - Tissue engineering in fractured mandible reconstruction.
AB  - The paper presents an overview of human tissue engineering and modelling
      simulating methods currently in use. Tissue engineering is a promising
      alternative for the reconstruction of altered or totally damaged biological
      tissue, applied to eliminate the complications associated to traditional
      transplants.

PMID- 19745421
TI  - An internet-based simulation system for training and development of regional
      healthcare-centers managers.
AB  - RHCMS (Regional Healthcare Center Management System) is an Internet-based
      simulation training system for Regional Healthcare-Centers (RHCs) managers. The
      system is based on an integrative model, designed and developed by an
      interdisciplinary team of experts, for the purpose of training and developing
      RHCs' managers. This model involves the study of the following fields: healthcare
      management, business administration, organizational behavior, health economics,
      management science, and information technologies. The simulation system enables
      the operation of a management decision-making game. In the game, teams of
      trainees, playing management teams of RHCs, within one specific community,
      compete among themselves. The simulation focuses on managerial performance, based
      on periodic team-decisions, within the internal and external environmental
      context. The simulation game has a major potential contribution in enabling
      management trainees to transfer theoretical knowledge into managerial practical
      tools, capabilities and skills.

PMID- 19745422
TI  - Fractal behaviour of heart rate variability reflects severity in stroke patients.
AB  - Non-linear parameters obtained from heart rate variability (HRV) analysis has
      recently been recognized to provide valuable information for physiological
      interpretation of heart rate fluctuation. Among the numerous non-linear
      parameters related to the fractal behaviour of the HRV signal, two classes have
      gained wide interest in the last years: the beta exponent based on the 1/f-like
      relationship, starting from the spectral power, and that based on fractal
      dimension. In order to evaluate the relationship between lesion's severity and
      fractal behaviour, 20 first-ever stroke subjects and 10 healthy subjects were
      studied. Patients were divided in two groups according to single or multiple
      medium cerebral artery lesions. All subjects underwent 24-hour Holter recording
      analysed by fractal and 1/f-like techniques. Differently from methods usually
      used in literature to evaluate the fractal dimension (FD), in this work the FD
      was extracted by using the Higuchi's algorithm that permits to calculate the
      parameter directly from the HRV sequences in the time domain. Results show that
      fractal analysis contains relevant information related to different HRV dynamics
      that permits to separate normal subjects from stroke patients. FD is also able to
      distinguish between normal and stroke subjects with different lesion's severity.

PMID- 19745423
TI  - Control of dexterous bio-prosthetic hand via sequential recognition of EMG
      signals using fuzzy relations.
AB  - The paper presents a concept of bio-prosthesis control via recognition of user
      intent on the basis of myopotentials acquired of his body. We assume that in the
      control process each prosthesis operation consists of specific sequence of
      elementary actions. The contextual (sequential) recognition is considered in
      which the fuzzy relation approach is applied to the construction of a classifying
      algorithm. Experimental investigations of the proposed algorithm for real data
      are performed and results are discussed.

PMID- 19745424
TI  - Simulation of the usage of Gaussian mixture models for the purpose of modelling
      virtual mass spectrometry data.
AB  - This article presents the method of the processing of mass spectrometry data.
      Mass spectra are modelled with Gaussian Mixture Models. Every peak of the
      spectrum is represented by a single Gaussian. Its parameters describe the
      location, height and width of the corresponding peak of the spectrum. An
      authorial version of the Expectation Maximisation Algorithm was used to perform
      all calculations. Errors were estimated with a virtual mass spectrometer. The
      discussed tool was originally designed to generate a set of spectra within
      defined parameters.

PMID- 19745425
TI  - Virtual model of the human brain for neurosurgical simulation.
AB  - The aim of this work is to develop a realistic virtual model of the human brain
      that could be used in a neurosurgical simulation for both educational and
      preoperative planning purposes. The goal of such a system would be to enhance the
      practice of surgery students, avoiding the use of animals, cadavers and plastic
      phantoms. A surgeon, before carrying out the real procedure, will, with this
      system, be able to rehearse by using a surgical simulator based on detailed
      virtual reality models of the human brain, reconstructed with real patient's
      medical images. In order to obtain a realistic and useful simulation we focused
      our research on the physical modelling of the brain as a deformable body and on
      the interactions with surgical instruments. The developed prototype is based on
      the mass-spring-damper model and, in order to obtain deformations similar to the
      real ones, a three tiered structure has been built. In this way, we have obtained
      local and realistic deformations using an ad-hoc point distribution in the volume
      where the contact between the brain surface and a surgical instrument takes
      place.

PMID- 19745426
TI  - Fuzzy-based extraction of vascular structures from time-of-flight MR images.
AB  - In this paper an automatic fuzzy based method for the extraction of the
      cerebrovascular system from 3D Time-of-Flight (TOF) MRA image sequences is
      presented. In order to exclude non-brain tissue an automatic skull stripping
      method is applied in a preprocessing step. Based on the TOF images vesselness and
      maximum parameter images are computed first. These parameter images are then
      combined with the TOF sequence using a fuzzy inference. The resulting fuzzy image
      offers an improved enhancement of small as well as malformed vessels against the
      remaining brain. Finally, the fuzzy-connectedness approach is used to extract the
      vascular system. A first evaluation showed that the fuzzy-based method proposed
      performs better than a state of the art method and yields results in the range of
      the inter-observer variation.

PMID- 19745427
TI  - A visualisation tool for augmenting assessment of ankylosing spondylitis.
AB  - Ankylosing Spondylitis (AS) is a chronic condition which requires clinical
      assessment to inform the management of AS, the intent being to alleviate the
      symptoms and to improve the health of the suffering person. An integral part of
      the current assessment is the measurements taken of a number of subjective and
      objective factors that affect the person's health status. There is growing
      awareness that the protocols and means of taking the measurements are both
      inaccurate and inconsistent. This paper addresses how such assessments may be
      augmented by utilizing 3-dimensional visualisation technology to collect and
      present data of this multifaceted condition. The final goal of the research is to
      provide a relevant tool for AS that can be used in both clinical and home
      settings. It is designed to directly support the therapeutic regime, to enhance
      assessment, to provide meaningful feedback to both AS sufferers and clinicians
      alike and to facilitate the collection of objective evidence relating to the
      condition.

PMID- 19745428
TI  - Enabling interoperability, accessibility and reusability of virtual patients
      across Europe - design and implementation.
AB  - Virtual Patients (VPs) have successfully been integrated into medical and
      healthcare curricula for a number of years. Lack of time and resources is a
      frequently reported problem encountered when developing VPs for teaching and
      learning. Consequently there is a need for cross-institutional repositories of
      VPs. The aims of the study were two-fold: to enable interoperability between
      virtual patient systems and to investigate if (and how) an application profile is
      implemented in four different types of VP systems. This European collaborative
      implementation of a blend of several specifications (Medbiquitous VP XML,
      Medbiquitous Healthcare LOM, and SCORM) is innovative and the study has shown a
      variation in how the application profile could be implemented.

PMID- 19745429
TI  - An approach to calculate and visualize intraoperative scattered radiation
      exposure.
AB  - During the intraoperative radiograph generation process with mobile image
      intensifier systems (C-arm) most of the radiation exposure for patient, surgeon
      and operation room personal is caused by scattered radiation. The intensity and
      propagation of scattered radiation depend on different parameters, e.g. the
      intensity of the primary radiation, and the positioning of the mobile image
      intensifier. Exposure through scattered radiation can be minimized when all these
      parameters are adjusted correctly. Because radiation is potentially dangerous and
      could not be perceived by any human sense the current education on correct
      adjustment of a C-arm is designed very theoretical. This paper presents an
      approach of scattered radiation calculation and visualization embedded in a
      computer based training system for mobile image intensifier systems called virtX.
      With the help of this extension the virtX training system should enrich the
      current radiation protection training with visual and practical training aspects.

PMID- 19745430
TI  - Visual assessment of endemic nephropathy markers relationship.
AB  - The aim of this paper was to assess relationship between possible endemic
      nephropathy (EN) markers visually by the CoPlot methodology, and to illustrate
      this promising data analysis approach. From 912 screened persons in 3 Croatian
      endemic villages, 25 persons were diagnosed as confirmed EN patients, 371 as non
      EN, and the remainder were classified as suspected of having EN, or at risk. Data
      on 25 confirmed EN patients were matched with appropriate non-EN examinees. All
      records with missing data were excluded, resulting in 35 subjects with complete
      data on the 13 key EN variables for CoPlot mapping. CoPlot solution met the
      accepted goodness of fit measure thresholds. Result showed relationship between
      EN markers, identifying some nearly duplicated variables, and possible outliers
      needing some subsequent analysis.

PMID- 19745431
TI  - Combination of visual and textual similarity retrieval from medical documents.
AB  - Medical visual information retrieval has been an active research area over the
      past ten years as an increasing amount of images are produced digitally and have
      become available in patient records, scientific literature, and other medical
      documents. Most visual retrieval systems concentrate on images only, but it has
      become apparent that the retrieval of similar images alone is of limited
      interest, and rather the retrieval of similar documents is an important domain.
      Most medical institutions as well as the World Health Organization (WHO) produce
      many complex documents. Searching them, including a visual search, can help
      finding important information and also facilitates the reuse of document content
      and images. The work described in this paper is based on a proposal of the WHO
      that produces large amounts of documents from studies but also for training. The
      majority of these documents are in complex formats such as PDF, Microsoft Word,
      Excel, or PowerPoint. Goal is to create an information retrieval system that
      allows easy addition of documents and search by keywords and visual content. For
      text retrieval, Lucene is used and for image retrieval the GNU Image Finding Tool
      (GIFT). A Web 2.0 interface allows for an easy upload as well as simple
      searching.

PMID- 19745432
TI  - On signal analysis of three-dimensional nystagmus.
AB  - Nystagmus needs to be stimulated for healthy subjects, but in patients it can
      also be spontaneous. By recording spontaneous nystagmus it is possible to reveal
      underlying disorders of the semicircular canals of the inner ear. We developed a
      signal analysis technique for this purpose and tested it with 28 otoneurological
      patients who had disorders in their semicircular canals. Our test results support
      the postulate how nystagmus should appear under these conditions and agree with
      results presented in the otoneurological literature.

PMID- 19745433
TI  - Similarity-based motion tracking of cells in microscopic images.
AB  - Live-cell assays are used to study the dynamic functional cellular processes in
      high-content screening of drug discovery processes. The large amount of image
      data created during the screening requires automatic image-analysis procedures
      that can describe these dynamic processes. One class of tasks in this application
      is the tracking of cells and the description of the events and the changes in the
      cell characteristics so that the desired information can be extracted from it
      based on data-mining and knowledge-discovery methods. In this paper, we propose a
      similarity-based approach for motion detection of the entire cell. Results are
      given on a test series from a real drug discovery process.

PMID- 19745434
TI  - A data model for handling whole slide microscopy images in picture archiving and
      communications systems.
AB  - Extremely large medical images, like ones of virtual slide microscopy, are beyond
      some limitations of the DICOM standard (e.g., a 4 Gbyte barrier, caused by 32-bit
      architecture). Some solutions and trade-offs have been already proposed and
      included in the DICOM standard (e.g., usage of JPEG2000 image compression
      standard, JPEG2000 interactive protocol [JPIP] and division of the images into
      smaller parts for placing them in the PACS). These new features lead to
      implementation of alternative interaction solutions simultaneously in the same
      PACS to serve both images of typical size (e.g., radiological) and large size
      virtual slide microscopy images. The paper deals with problems of (a)
      constructing a data and interaction model of images within PACS, (b) searching
      for criteria to assess image content complexity and to reach an efficient
      division of virtual slide microscopy images into tiles; (c) providing both the
      conventional DICOM services and the image interchange using JPIP.

PMID- 19745435
TI  - Reversible anonymization of DICOM images using automatically generated policies.
AB  - Many real-world applications in the area of medical imaging like case study
      databases require separation of identifying (IDATA) and non-identifying (MDATA)
      data, specifically those offering Internet-based data access. These kinds of
      projects also must provide a role-based access system, controlling, how patient
      data must be organized and how it can be accessed. On DICOM image level,
      different image types support different kind of information, intermixing IDATA
      and MDATA in a single object. To separate them, it is possible to reversibly
      anonymize DICOM objects by substituting IDATA by a unique anonymous token. In
      case that later an authenticated user needs full access to an image, this token
      can be used for re-linking formerly separated IDATA and MDATA, thus resulting in
      a dynamically generated, exact copy of the original image. The approach described
      in this paper is based on the automatic generation of anonymization policies from
      the DICOM standard text, providing specific support for all kinds of DICOM
      images. The policies are executed by a newly developed framework based on the
      DICOM toolkit DCMTK and offer a reliable approach to reversible anonymization.
      The implementation is evaluated in a German BMBF-supported expert network in the
      area of skeletal dysplasias, SKELNET, but may generally be applicable to related
      projects, enormously improving quality and integrity of diagnostics in a field
      focused on images. It performs effectively and efficiently on real-world test
      images from the project and other kind of DICOM images.

PMID- 19745436
TI  - Tele-surgery: a new virtual tool for medical education.
AB  - The rapid evolution of telecommunication technology has enabled advances to be
      made in low cost video-conferencing through the improvement of high speed
      computer communication networks and the enhancement of Internet security
      protocols. As a result of this progress, eHealth education programs are becoming
      a reality in universities, providing the opportunity for students to have greater
      interaction at live surgery classes by means of virtual participation.
      Undergraduate students can be introduced to new concepts of medical care, remote
      second opinion and to telecommunication systems, whilst virtually experiencing
      surgical procedures and lectures. The better access this provides to the
      operating theater environment, the patient and the surgeon can improve the
      learning process for students. An analogical system was used for this
      experimental pilot project due to the benefits of it being low cost with a
      comparatively easy setup. The tele-surgery lectures were also transmitted to
      other universities by means of a Pentium 4 computer using open source software
      and connected to a portable image acquisition device located in the Sao Lucas
      University Hospital. Telemedicine technology has proven to be an important
      instrument for the improvement of medical education and health care. This study
      allowed health professionals, professors and students to have greater interaction
      during surgical procedures, thus enabling a greater opportunity for knowledge
      exchange.

PMID- 19745437
TI  - Digital techniques in experimental medicine.
AB  - Color Doppler and intravenous angiography (digital technique) can widely be used
      in experimental medicine. Their wide clinical application, availability,
      simplicity and small cost impose their importance. Color Doppler analysis of the
      vascular activity of certain region is more precise than the classic intravenous
      angiography, but requires contact of highly sophisticated equipment with the
      experimental animal. Intravenous angiography gives somewhat rougher image, but is
      more available and does not require the potentially unwanted contact. In this
      research, we used both methods to mark the vein bypass of the modified infrahyoid
      lobe dissected from the dog (used as experimental animal). We marked the
      horizontally placed vein bypass at the level of the thong bone using Color
      Doppler and intravenous angiography. Applied vein bypass performed the vein
      drainage of the modified infrahyoid lobe. Results obtained with these two
      diagnostic methods were compared with the pathohistological (PH) analysis.
      Results obtained using Color Doppler (using the probe GE Vivid 3 frequency of 5
      to 12 MHz) were somewhat closer to the results of PH analysis which we consider
      as the most objective. Result obtained using intravenous angiography (digital
      technique using the Siemens Siregraph machine) were satisfactory in marking the
      required blood vessel for the experiment. Color Doppler and intravenous
      angiography as digital diagnostic procedures in experimental surgery are usable
      and as such significantly objective, widely available and do not require
      additional financial investments.

PMID- 19745438
TI  - Designing a socio-economic assessment method for integrative biomedical research:
      the Osteoporotic Virtual Physiological Human project.
AB  - In integrative biomedical research, methods assessing the clinical or even socio
      economic impact of more complex technologies such as Information and
      Communication Technology (ICT)-based tools for modelling and simulation of human
      physiology have rarely been applied. The EU funded Osteoporotic Virtual
      Physiological Human (VPHOP) research project, part of the Virtual Physiological
      Human (VPH) European initiative, will create a patient-specific hypermodel to
      predict the absolute risk of bone fracture much more accurately than predictions
      based on current clinical practice. The project has developed an innovative,
      multilevel generic methodological framework to assess the clinical and socio
      economic impact of biocomputational models. The assessment framework consists of
      three components: a socio-economic cost benefit analysis, health economic
      analysis of care pathways, and disease cost simulation models. Through its
      holistic perspective, the method provides a tool to appraise the overall value of
      biocomputational models for society.

PMID- 19745439
TI  - Bringing electronic patient records into health professional education: towards
      an integrative framework.
AB  - In this paper we discuss our approach for integrating electronic patient records
      into health professional education. Electronic patient record (EPR) use is
      increasing globally. The EPR is considered the cornerstone of the modernization
      and streamlining of healthcare worldwide. However, despite the importance of the
      EPR, health professional education in much of the world provides health
      professional students (who will become the practicing health professionals of the
      future) with limited access or knowledge about the EPR. New ways of exposing
      students to EPRs will be needed in order to ensure that health professionals will
      adopt and use this complex technology wisely and effect the positive benefits
      EPRs are expected to bring to healthcare globally. In this paper we describe: (a)
      a framework we have developed for integrating EPRs into health professional
      education and (b) an innovative Web portal, known as the University of Victoria
      Electronic Health Record (EHR) Educational Portal (which houses a number of EPRs)
      that can be used to explore the integration of EPRs in health professional
      education. It is hoped that adoption and use of EPRs will ultimately be improved
      through the use of the portal to allow students virtual and ubiquitous access to
      example EPRs, coupled with principled educational approaches for integrating EPR
      technology into health professional curricula.

PMID- 19745440
TI  - Bringing electronic patient records into health professional education: software
      architecture and implementation.
AB  - This paper describes the implementation of an Electronic Medical Record (EMR)
      which has been redesigned specifically for the purposes of teaching medical and
      other health professional students. Currently available EMR software is designed
      specifically for use in actual practice settings and not for the needs of
      students and educators. The authors identified many unique requirements of an EMR
      in order to satisfy the educational goals unique to the electronic medium. This
      paper describes the specific architecture and many of the unique features of the
      EMR implemented for the University of British Columbia (UBC) Medical School
      program for teaching medical students. This implementation describes 200
      participating students participating in a hands-on use of an EMR with a single
      standardized patient case. The participating students were distributed across
      three physical sites in the Province of British Columbia UBC curricula in
      December, 2007.

PMID- 19745441
TI  - An investigation of factors influencing healthcare workers' use and acceptance of
      e-learning in post-school healthcare education.
AB  - The objective of the study presented here was to perform an empirical
      investigation on factors affecting healthcare workers acceptance and utilisation
      of e-learning in post-school healthcare education. E-learning benefits are
      realised when key features of e-learning are not only applied, but deemed useful,
      compatible with the learning process and supportive in order to reach the overall
      goals of the learning process. We conducted a survey of 14 state-enrolled nurses
      and skilled-workers within the field of healthcare in Norway. The results show
      that perceived compatibility and subjective norm explain system usage of the e
      learning tool amongst the students. We found that the fact that the students
      considered the e-learning to be compatible with the course in question had a
      positive effect on e-learning tool usage. We also found support for factors such
      as facilitating conditions and ease of use leads to the e-learning tool being
      considered useful.

PMID- 19745442
TI  - Quality assessment of medical education and use of information technology.
AB  - Extensive and fast advancements in biomedical sciences created a significant
      delay in receiving relevant and updated information in medical practice -
      physicians use old techniques and treat patients incorrectly. Bosnia and
      Herzegovina signed the Bologna Declaration on 18 September 2003, and in the light
      of this new approach to university education, and the process of joining The
      European Union, the authors set the following aims: to determine the current
      level of knowledge among medical students at the Medical Faculty of the
      University of Sarajevo, to determine the level of knowledge among medical
      students before their enrolment at the faculty, and to find out students opinion
      on their needs for further education. Students also left their suggestions on
      what should be changed in the curriculum. 203 students were included in the
      survey and results show that they demand more practical work, direct contact with
      patients and presentation of interesting clinical cases. Many of them use the
      internet as professional education means. Professional papers are rarely used. At
      present, the availability of learning material is insufficient at the faculty
      library.

PMID- 19745443
TI  - Challenges and opportunities of using recommender systems for personalized health
      education.
AB  - The use of computers in health education started more than a decade ago, mainly
      for tailoring health educational resources. Nowadays, many of the computer
      tailoring health education systems are using the Internet for delivering
      different types of health education. Traditionally, these systems are designed
      for a specific health problem, with a predefined library of educational
      resources. These systems do not take advantage of the increasing amount of
      educational resources available on the Internet. One of the reasons is that the
      high availability of content is making it more difficult to find the relevant
      one. The problem of information overload has been addressed for many years in the
      field of recommender systems. This paper is focused on the challenges and
      opportunities of merging recommender systems with personalized health education.
      It also discusses the usage of social networks and semantic technologies within
      this approach.

PMID- 19745444
TI  - E-learning to train staff in Danish hospitals - three genres of e-learning.
AB  - This paper presents a study of the use of e-learning in education and training of
      hospital staff in Denmark, in particular in relation with the implementation of
      electronic patient records (EPR). The study consists of a survey mapping the
      dissemination and main experience from using e-learning in Danish hospitals. The
      study shows a widespread use and a considerably agreement on the potentials of e
      learning in education and training of hospital staff, but also problems and
      doubtfulness concerning the actual role of e-learning in the overall educational
      and organizational strategy for the hospital. The majority of hospitals use some
      sorts of computer-based training program to support the staff in acquiring
      necessary knowledge to operate the EPR. I argue that a more differentiated
      understanding is needed in order to realize the potentials and direct the use of
      e-learning in hospitals. Three genres of e-learning which differ in regards to
      qualification addressed are identified and I claim that a more explicit
      understanding of the differences between them is needed in order to guide the
      choice of e-learning of hospital staff.

PMID- 19745445
TI  - Novice nurse information needs in paper and hybrid electronic-paper environments:
      a qualitative analysis.
AB  - A within group, laboratory, experimental study of nurse information seeking was
      conducted. As a part of the study, 35 novice nurses assessed and planned the care
      of two patients in two simulation environments: a paper (PR) environment and a
      hybrid (HY) environment [i.e., part of the environment was made available in
      electronic form via an electronic patient record (EPR) and part of it was paper
      based]. Subjects were asked to "think aloud" in each environment and participated
      in a cued recall session following participation in the simulations. Subjects'
      verbalizations and actions were audio and video recorded and then transcribed. In
      the first phase of the study audio and video data were qualitatively coded using
      Model Based Coding with concepts from Newcomer Information Seeking Theory (NIST).
      This paper presents the qualitative results of this study with a focus upon the
      types of information used by novice nurses during the assessment and planning of
      patient care. Qualitative findings revealed novice nurses used referent,
      relational and appraisal information (as predicted by NIST theory and research)
      including information composed of more than one type of information (e.g.,
      referent-relational). Two new types of information emerged from the qualitative
      data - situational task and situational organization information.

PMID- 19745446
TI  - E-learning for nurse continuous education.
AB  - The paper compares the effectiveness of a traditional residential and an e
      learning course for nurses, and suggests ways to identify the psychological
      characteristics which might lead people to prefer e-learning education.

PMID- 19745447
TI  - Improvement of knowledge and practical skills in venipuncture through web-based
      training.
AB  - This paper reports on the implementation of web-based training in venipuncture as
      standardizable knowledge transfer. For this purpose, we performed an experimental
      study with nursing students and medical students.

PMID- 19745448
TI  - Usage and effectiveness of e-learning courses for continuous medical education.
AB  - The paper describes the results of an e-learning experimental project for
      Continuous Medical Education (CME) in Occupational Medicine in terms of: extent
      of the e-learning courses usage by the healthcare personnel, knowledge
      acquisition and satisfaction. 11 courses have been available for 11 months during
      which 2,034 users all over Italy enrolled in 5,183 courses with a success
      percentage of 72% and a significant difference between test scores performed
      before and after attending the e-learning courses. Also user's satisfaction,
      inspected through a questionnaire, has provided good results. Starting from the
      experience reported, the authors are confident that e-learning will gain ground
      and evolve as an effective and appreciated educational mean for CME.

PMID- 19745449
TI  - Computer laboratory in medical education for medical students.
AB  - Five generations of second year students at the Zagreb University School of
      Medicine were interviewed through an anonymous questionnaire on their use of
      personal computers, Internet, computer laboratories and computer-assisted
      education in general. Results show an advance in students' usage of information
      and communication technology during the period from 1998/99 to 2002/03. However,
      their positive opinion about computer laboratory depends on installed capacities:
      the better the computer laboratory technology, the better the students'
      acceptance and use of it.

PMID- 19745450
TI  - An ECG analysis interactive training system for understanding arrhythmias.
AB  - The ECG remains a daily diagnostic tool for the detection of numerous
      cardiovascular diseases. Our goal was to use a computerized qualitative model
      (QM) of heart in order to build cases of simple arrhythmias dedicated to initial
      and more advanced medical teaching. The original QM is able to generate
      videograms of many cardiac disturbances. A Flash player is used to view ECG,
      synchronous Lewis diagram and chromatic 2D cardiac animation of a specific case.
      OAAT is a standardized 18 yes/no answers questionnaire which allows the learner
      to diagnose five main types of arrhythmias that can be compared with normal sinus
      rhythm (NSR) analysis. This new tool has been recently used by medical students
      during practical sessions. Based on medical reasoning learning on NSR video and
      upon trying to recognize an abnormal cardiac rhythm, all users can reach the 100%
      winning score since they can perform as many attempts as they like. We believe
      that unlimited case review with questionnaire answering, ECG and Lewis diagram
      replay and step-by-step visualization of the abnormal propagation of the cardiac
      impulse on the 2D heart videos are a highly efficient means to help students
      understand even complex arrhythmic mechanisms.

PMID- 19745451
TI  - Towards the integration of medical informatics education for clinicians into the
      medical curriculum.
AB  - In the context of an existing first year, one-semester mandatory course of
      medical informatics (MI) for medical students, we tested an interactive teaching
      approach in parallel with the traditional academic program. After six semesters
      (at the beginning of the clinical stage) we collected feedback from the former
      students in the two parallel programs (with anonymous questionnaires comprising
      both subjectively-rated items and open-ended questions). We conclude that an
      introductory course on information and communication technology and information
      skills can be useful at the beginning of the medical curriculum, while an
      interactive, problem-based-learning-type MI course should be included during the
      clinical stage. Early development of these skills, and their use/utility across
      the curriculum, are important aspects of integrating MI education into clinical
      training.

PMID- 19745452
TI  - Open source technologies for dyslexic pupils.
AB  - We describe how Open Source applications can be used to achieve aids for the
      integration at school of pupils suffering from dyslexia. The experience is based
      on speech synthesis tools, Festival and MBROLA, and requires a trilingual
      installation, supporting speech synthesis for Italian, German and English. Work
      is at present on going within some pilot schools of the Autonomous Province of
      Bolzano/Bozen, Italy.

PMID- 19745453
TI  - Task force of the EFMI journals: background, rationale and purpose.
AB  - The paper presents an analysis of how EFMI disseminates new knowledge and the
      active medical informatics journals in EFMI member countries was carried out as
      an outcome of the EFMI Council meeting in London in 2008. The analysis identifies
      eight active major informatics journals and a several other publications. Most
      are subscription-based and are published at least quarterly. There is a
      possibility for the editors to meet regularly and form a community of practice
      with the aim of further improving their effectiveness in disseminating new
      knowledge and best practice in medical informatics. It is feasible to share
      expertise and it may be possible to harmonise several aspects of preparation and
      submission of manuscripts so that some identified barriers in publishing are
      reduced.

PMID- 19745454
TI  - The role of ontologies for sustainable, semantically interoperable and
      trustworthy EHR solutions.
AB  - As health systems around the world turn towards highly distributed, specialized
      and cooperative structures to increase quality and safety of care as well as
      efficiency and efficacy of delivery processes, there is a growing need for
      supporting communication and collaboration of all parties involved with advanced
      ICT solutions. The Electronic Health Record (EHR) provides the information
      platform which is maturing towards the eHealth core application. To meet the
      requirements for sustainable, semantically interoperable, and trustworthy EHR
      solutions, different standards and different national strategies have been
      established. The workshop summarizes the requirements for such advanced EHR
      systems and their underlying architecture, presents different strategies and
      solutions advocated by corresponding protagonists, discusses pros and cons as
      well as harmonization and migration strategies for those approaches. It
      particularly highlights a turn towards ontology-driven architectures. The
      workshop is a joint activity of the EFMI Working Groups "Electronic Health
      Records" and "Security, Safety and Ethics".

PMID- 19745455
TI  - Introducing guidelines for good evaluation practice in health informatics.
AB  - Good evaluation practice guidelines have been developed through a consensus
      making process by a core team and the health informatics community. A set of 60
      issues has been identified that is relevant for planning, implementation and
      execution of an evaluation study in the health informatics domain. These issues
      cover all phases of an evaluation study: Study exploration, first study design,
      operationalization of methods, detailed study design, execution and finalization
      of an evaluation study. Issues of risk management and project control are also
      addressed in the guidelines. Through application of these guidelines the general
      validity and generalization of evaluation studies are likely to be increased,
      since these guidelines aim at avoiding a number of omissions, pitfalls and risks.

PMID- 19745456
TI  - Open source and healthcare in Europe - time to put leading edge ideas into
      practice.
AB  - Free/Libre and Open Source Software (FLOSS) is a process of software development,
      a method of licensing and a philosophy. Although FLOSS plays a significant role
      in several market areas, the impact in the health care arena is still limited.
      FLOSS is promoted as one of the most effective means for overcoming fragmentation
      in the health care sector and providing a basis for more efficient, timely and
      cost effective health care provision. The 2008 European Federation for Medical
      Informatics (EFMI) Special Topic Conference (STC) explored a range of current and
      future issues related to FLOSS in healthcare (FLOSS-HC). In particular, there was
      a focus on health records, ubiquitous computing, knowledge sharing, and current
      and future applications. Discussions resulted in a list of main barriers and
      challenges for use of FLOSS-HC. Based on the outputs of this event, the 2004 Open
      Steps events and subsequent workshops at OSEHC2009 and Med-e-Tel 2009, a four
      step strategy has been proposed for FLOSS-HC: 1) a FLOSS-HC inventory; 2) a FLOSS
      HC collaboration platform, use case database and knowledge base; 3) a worldwide
      FLOSS-HC network; and 4) FLOSS-HC dissemination activities. The workshop will
      further refine this strategy and elaborate avenues for FLOSS-HC from scientific,
      business and end-user perspectives. To gain acceptance by different stakeholders
      in the health care industry, different activities have to be conducted in
      collaboration. The workshop will focus on the scientific challenges in developing
      methodologies and criteria to support FLOSS-HC in becoming a viable alternative
      to commercial and proprietary software development and deployment.

PMID- 19745457
TI  - Patient safety: detection and prevention of adverse drug events.
AB  - Adverse Drug Events (ADE) represent a key problem in Public Health. The detection
      and prevention of ADE is a real challenge for hospitals and healthcare
      professionals. Healthcare Information and Communication Technologies can
      contribute to reduce the incidence of preventable ADE. During this workshop, we
      will discuss the various aspects of detection of ADE through methods like data
      and semantic mining in medical databases; the possibility of preventing ADE by
      using clinical decision support systems; the importance of Human Factors
      Engineering and the contextualization of knowledge. Examples and demonstrations
      will come from the European Project PSIP, devoted to the detection and prevention
      of ADE in Hospitals.

PMID- 19745458
TI  - Planning for national health information system evaluation.
AB  - Most EU member states have a documented policy on eHealth. Documented follow-up
      and evaluation policies to assess reaching of the set aims, as well as evaluating
      outcomes of implemented systems at a national level are, however, rare.
      Methodologies for large scale information system assessment and evaluation are
      poorly established. In the workshop, the Finnish evaluation plans for the
      National Health Information System (NHIS) are used as a case in the workshop to
      reflect on core issues and challenges in large-scale evaluation for supporting
      system development, implementation and positive impacts. The results of the
      discussions are documented to be used in further refinement of the Finnish
      evaluation methodology and for enhancing networking of respective parties in
      different countries. The results will also benefit participants including policy
      makers, developers and researchers of national eHealth systems in pursuit of
      national evaluation activities.

PMID- 19745459
TI  - Health care process and workflow in continuity of care.
AB  - Basically, the workshop aims to raise and collect input to Part 2 ("Health care
      process and workflow"), currently under development, of the European standard EN
      13940 "Health informatics - System of concepts to support continuity of care",
      the general objective of which is to enable communication at the semantic level
      between information systems in health care in the perspective of continuity of
      care. Its scope encompasses identifying the various processes and process objects
      involved, taking into consideration resource management aspects, responsibilities
      of health care providers, and means for patients' participation. While the
      process description and concept system model is meant as a tool for the
      development of information systems, it may also be used for enterprise analysis
      and form the basis for organizational decisions and more widely organizational
      developments that are not inherently tied to the use of ICT.

PMID- 19745460
TI  - HL7's comprehensive standards set and its international collaboration for
      enabling semantically interoperable eHealth and pHealth solutions.
AB  - The workshop is organized by HL7 and its affiliates to present and to discuss
      HL7's activities for providing international standards and specifications to
      enable advanced semantically interoperable eHealth and pHealth solutions,
      adaptable to national health systems through localization. The workshop
      especially focuses on the multi-disciplinary structure of HL7 and its liaisons
      with international and national standards developing organizations as well as
      important health informatics initiatives. Demonstrating existing and emerging
      solutions and strategies within HL7's broad scope and spectrum, the international
      scope of HL7 standards is highlighted.

PMID- 19745461
TI  - Nanoinformatics: new challenges for biomedical informatics at the nano level.
AB  - Over the last decades Nanotechnology has promised to advance science and
      technology in many areas. Within medicine, Nanomedicine promises to deliver new
      methods for diagnosis, prognosis and therapy. As the amount of available
      information is rapidly growing, new Biomedical Informatics approaches have to be
      developed to satisfy the increasing demand on data and knowledge management. In
      2007, a new sub-discipline, already named "Nanoinformatics", was created with
      support from the US National Science Foundation. In Europe, a project named
      ACTION-Grid was launched in 2008 with support from the European Commission to
      analyze the challenges and agenda for developing Nanoinformatics as a discipline
      related to Nanotechnology, Biomedicine and Informatics. For MIE 2009, members of
      this consortium proposed a workshop to discuss the scientific and strategic
      issues associated with this topic. Nanoinformatics aims to create a bridge
      between Nanomedicine and Information Technology applying computational methods to
      manage the information created in the nanomedical domain.

PMID- 19745462
TI  - A transformation in health sciences education: a description of health sciences
      online.
AB  - In this article, we describe what we expect will be a substantive transformation
      in health sciences education: Health Sciences Online (www.hso.info). HSO is the
      first website that delivers authoritative, comprehensive, free, and ad-free
      health sciences knowledge. It is a portal to the best health sciences knowledge,
      and the foundation of what we expect to be the most accessible, high-quality
      health sciences university. This article describes the site and the resources
      currently available through HSO, and our plans for further development of this
      resource.

PMID- 19745463
TI  - Digital pathology in Europe: coordinating patient care and research efforts.
AB  - The COST Action IC0604 "Telepathology Network in Europe" (EURO-TELEPATH) is an
      initiative of the COST (European Cooperation in the field of Scientific and
      Technical Research) framework, supported by the Seventh Framework Programme for
      research and technological development (FP7), of the European Union will be
      running from 2007 to 2011 and is aimed to coordinate research efforts to develop
      the most adequate technological framework for the management of multimedia
      electronic healthcare records (data and images) applied to Anatomic Pathology.
      Sixteen countries are participating in EURO-TELEPATH. Activities are organized in
      four Working Groups (WGs): WG1 - Pathology Business Modeling, WG2 - Informatics
      Standards in Pathology, WG3 - Images: Analysis, Processing, Retrieval and
      Management, and WG4 - Technology and Automation in Pathology. During the first
      year of work, the collaboration between software engineers, computer scientists,
      pathologists and other clinicians has been essential to detect three main areas
      of interest in digital pathology research: virtual microscopy scanning solutions,
      health informatics standards, and image processing and analysis. Research in
      these areas is essential to a correct approach to telepathology, including
      primary diagnosis, and secondary or teleconsultation services. Managing
      microscopic pathology images (virtual slides) is a challenge to existing
      information systems, mainly due to its large size, large number, and complex
      interpretation. Regarding interoperability, the integration of pathology reports
      and images into eHealth records is an essential objective that research groups
      should consider. Promoting participation in standards bodies (DICOM, IHE, HL7,
      IHTSDO) is an essential part of the project work. Understanding the business
      process of pathology departments in daily practice, including healthcare,
      education, research, and quality control activities, is the starting point to be
      sure that standardization efforts converge with user needs. Following a recent
      IHE proposal, coordination with public health services like national or regional
      tumor registries must also be supported. Virtual or digital slides are fostering
      the use of image processing and analysis in pathology not only for research
      purposes, but also in daily practice. Nowadays, further discussion is needed on
      the adequacy of current existing technical solutions, including for instance
      quality of images obtained by scanners, or the efficiency of image analysis
      applications.

PMID- 19745464
TI  - Is there a common background to support better healthcare in Central and South
      East Europe?
AB  - The workshop is proposed by the EFMI WG Health Informatics for Interregional
      Cooperation with the support of the Electronic Healthcare Records WG as a
      platform for finding common interests regarding improvement of healthcare
      services for the Central and East European geographical area. The goal is to
      assess conformance to international standards in healthcare and to find domains
      in which each country can provide best practices results of using ICT in support
      of healthcare.

PMID- 19745465
TI  - Archetype-based knowledge management for semantic interoperability of electronic
      health records.
AB  - Formal modeling of clinical content that can be made available internationally is
      one of the most promising pathways to semantic interoperability of health
      information. Drawing on the extensive experience from openEHR archetype research
      and implementation work, we present the latest research and development in this
      area to improve semantic interoperability of Electronic Health Records (EHRs)
      using openEHR (ISO 13606) archetypes. Archetypes as the formal definition of
      clinical content need to be of high technical and clinical quality. We will start
      with a brief introduction of the openEHR architecture followed by presentations
      on specific topics related to the management of a wide range of clinical
      knowledge artefacts. We will describe a web-based review process for archetypes
      that enables international involvement and ensures that released archetypes are
      technically and clinically correct. Tools for validation of archetypes will be
      presented, along with templates and compliance templates. All this in combination
      enables the openEHR computing platform to be the foundation for safely sharing
      the information clinicians need, using this information within computerized
      clinical guidelines, for decision support as well as migrating legacy data.

PMID- 19745466
TI  - Portable devices, sensors and networks: wireless personalized eHealth services.
AB  - The 21st century healthcare systems aim at involving citizen and health
      professionals alike entitling especially the citizens to take over a higher level
      of responsibility for their own health status. Applied technologies like, e.g.,
      Internet, notebooks, and mobile phones enable patients to actively participate in
      treatment and rehabilitation. It's not any longer just health cards; it's an
      ongoing standardized personalization of health services including application of
      portable devices, sensors and actuators stipulating the personalized health
      approach while offering chances for practicing high quality wireless personalized
      shared care. The path from cards to personalized and portable devices tackles
      aspects like health advisors, RFDI technology, the EHR, chips, and smart objects.
      It is important to identify criteria and factors determining the application of
      such personalized devices in a wirelessly operated healthcare and welfare, the
      paradigm change from cards to secure wireless devices to mobile sensors, and the
      citizen's acceptance of underlying technologies. The presentations of the
      workshop jointly organized by EFMI WG "Personal Portable Devices (PPD)" and
      ISO/IEC JTC 1 "Study Group on Sensor Networks (SGSN)" therefore aim at
      introducing technical approaches and standardization activities as well as
      emerging implementations in the addressed domain.

PMID- 19745467
TI  - Using an open source observational tool to measure the influence of the doctor's
      consulting style and the computer system on the outcomes of the clinical
      consultation.
AB  - Computerization of general practice is an international phenomenon. Many of the
      Electronic Patient Record (EPR) systems have developed organically with
      considerable variation in their interface and functionality. Consequently they
      have differing impact on the clinical consultation. There is a dearth of tools
      available to study their impact on the consultation. The objective is to use ALFA
      to film and analyze a simulated clinical consultation. We used the ALFA (Activity
      Log File Aggregation) open source toolkit, to make video based observation and
      analysis of the computer mediated consultation. ALFA enables precise comparison
      of core elements of EPR systems. It allows multiple video channels including
      screen capture, data about computer use, and verbal interactions to be
      synchronized, timed and navigated through for analysis. The toolkit is free and
      can be downloaded under an open source license from
      www.biomedicalinformatics.info/alfa/. Its outputs, which include Unified
      Modelling Language (UML), provide the evidence-base for assessing the impact of
      the computer on the consultation the designing of EPR systems. ALFA has been used
      to compare different brands of primary care computer systems; nurse case-load
      selection and consultation in psychiatry.

PMID- 19745468
TI  - Strategy for the future of health: goal formation and ITicine.
AB  - This article shows the importance of goal setting in strategy development and
      presents the Future of Health Technology Institute's www.fhti.org goals as an
      example of goals that have transformative power. It also provides synthesis and
      developmental history of the "Strategy for the Future of Health" book while
      examining collective book design as a strategy development tool. It emphasizes
      unprecedented technological revolution manifesting itself in the convergence of
      molecular biology, computer and medical science, electrical, mechanical, genetic
      and biomedical engineering (including cell, molecular and tissue engineering)
      resulting in the merger of information technology (IT) with medicine and the
      formation of "ITicine".

PMID- 19745469
TI  - Informatics and a health care strategy for the future--general directions.
AB  - Central problems in health care involve availability, access, quality, and cost.
      A major part of a health care strategy also involves disease prevention and
      promotion of healthy lifestyles, which go well beyond the purview of the health
      care system itself. Implementing any strategy involves health policy, finance,
      and management expertise. What then is the role of informatics? We take the
      position here that informatics is a key enabler both for addressing availability,
      access, quality, and cost, and also for supporting the work of health policy,
      finance, and management experts. Informatics provides the necessary information
      technology (IT) infrastructure, standards, tools, and data to be able to address
      these key topics and for carrying out the work of the experts. In that sense, we
      regard informatics as a means for social engineering--the availability of these
      capabilities brings stakeholders to the table who might otherwise not have reason
      to or be able to work together.

PMID- 19745470
TI  - Indistinguishable from magic: health and wellness in a future of sufficiently
      advanced technology.
AB  - We describe a future in which health and wellness are transformed by (1) the
      availability of definitive and unambiguous tests to prove or disprove each
      diagnosis, (2) new methods based in systems biology to help unravel the web of
      messages transmitted across cellular and subcellular networks, and (3) universal
      access to data that has been freed from data silos to produce true data liquidity
      for a constellation of purposes ranging from personal health management to
      population health research. We believe the resulting "connected health"
      environment will have a profound impact on every aspect of modern life.

PMID- 19745471
TI  - Designing the future of healthcare.
AB  - This paper describes the application of a holistic design process to a variety of
      problems plaguing current healthcare systems. A design process for addressing
      complex, multifaceted problems is contrasted with the piecemeal application of
      technological solutions to specific medical or administrative problems. The goal
      of this design process is the ideal customer experience, specifically the ideal
      experience for patients, healthcare providers, and caregivers within a healthcare
      system. Holistic design is shown to be less expensive and wasteful in the long
      run because it avoids solving one problem within a complex system at the cost of
      creating other problems within that system. The article applies this approach to
      the maintenance of good health throughout life; to the creation of an ideal
      experience when a person does need medical care; to the maintenance of personal
      independence as one ages; and to the enjoyment of a comfortable and dignified
      death. Virginia Mason Medical Center is discussed as an example of a healthcare
      institution attempting to create ideal patient and caregiver experiences, in this
      case by applying the principles of the Toyota Production System ("lean
      manufacturing") to healthcare. The article concludes that healthcare is
      inherently dedicated to an ideal, that science and technology have brought it
      closer to that ideal, and that design can bring it closer still.

PMID- 19745472
TI  - Strategies for positive outcomes: can information technology make a difference in
      health in Africa.
AB  - This chapter looks to the future through the prism of pilot projects well in
      progress at the time of this writing: use of a malaria electronic tutorial in
      Mifumi village, development of a mental health electronic tutorial in northern
      Uganda, and development of an electronic health management system at Tororo
      Hospital. Each demonstrates a strategy, rooted in African soil, whose ultimate
      objective is to improve health through IT and medical informatics. The projects
      connect users, health professionals, and decision-makers, bringing together
      interdisciplinary teams. These projects all seek to address the question: Can an
      information and communication technology (ICT) intervention make a difference in
      morbidity and mortality in African settings? The findings indicate that not only
      can these interventions be implemented but can be enhanced with community
      collaboration, making a positive outcome in terms of community adaptation more
      likely. Finally, this chapter proposes a health informatics center, a Menlo Park
      for innovation and entrepreneurship in East Africa in which new ICT inventions
      and interventions for better health can be created from around the region.

PMID- 19745473
TI  - Can consumers cure healthcare?
AB  - The U.S. healthcare delivery system is in crises. Costs are too high and
      increasingly becoming unaffordable to federal and state governments, employers
      and consumers. Americans are dissatisfied with the current system and believe it
      should be fundamentally altered or rebuilt. A solution needs to be found, and it
      is not the single-payer system espoused by many in Washington and elsewhere. We
      believe consumers can cure healthcare if (a) professionals, providers and policy
      experts shift their mindset from treating diseases and conditions to taking a
      holistic approach to the caring of people, particularly Baby Boomers and their
      parents; (b) technology becomes widely available to increase engagement,
      personalize healthcare, share experiences, make better choices and embrace
      convenience and (c) a cost-effective and reimbursed primary care navigator
      (coordinator and/or health manager), consistent with the medical home concept
      espoused by the American Association of Family Practitioners (AAFP) becomes a
      central component of public policy.

PMID- 19745474
TI  - Using reality mining to improve public health and medicine.
AB  - We live our lives in digital networks. We wake up in the morning, check our e
      mail, make a quick phone call, commute to work, buy lunch. Many of these
      transactions leave digital breadcrumbs--tiny records of our daily experiences.
      Reality mining, which pulls together these crumbs using statistical analysis and
      machine learning methods, offers an increasingly comprehensive picture of our
      lives, both individually and collectively, with the potential of transforming our
      understanding of ourselves, our organizations, and our society in a fashion that
      was barely conceivable just a few years ago. It is for this reason that reality
      mining was recently identified by Technology Review as one of "10 emerging
      technologies that could change the world". Many everyday devices provide the raw
      database upon which reality mining builds; sensors in mobile phones, cars,
      security cameras, RFID ('smart card') readers, and others, all allow for the
      measurement of human physical and social activity. Computational models based on
      such data have the potential to dramatically transform the arenas of both
      individual and community health. Reality mining can provide new opportunities
      with respect to diagnosis, patient and treatment monitoring, health services
      planning, surveillance of disease and risk factors, and public health
      investigation and disease control. Currently, the single most important source of
      reality mining data is the ubiquitous mobile phone. Every time a person uses a
      mobile phone, a few bits of information are left behind. The phone pings the
      nearest mobile-phone towers, revealing its location. The mobile phone service
      provider records the duration of the call and the number dialed. In the near
      future, mobile phones and other technologies will collect even more information
      about their users, recording everything from their physical activity to their
      conversational cadences. While such data pose a potential threat to individual
      privacy, they also offer great potential value both to individuals and
      communities. With the aid of data-mining algorithms, these data could shed light
      on individual patterns of behavior and even on the well-being of communities,
      creating new ways to improve public health and medicine. To illustrate, consider
      two examples of how reality mining may benefit individual health care. By taking
      advantage of special sensors in mobile phones, such as the microphone or the
      accelerometers built into newer devices such as Apple's iPhone, important
      diagnostic data can be captured. Clinical pilot data demonstrate that it may be
      possible to diagnose depression from the way a person talks--a depressed person
      tends to speak more slowly, a change that speech analysis software on a phone
      might recognize more readily than friends or family do. Similarly, monitoring a
      phone's motion sensors can also reveal small changes in gait, which could be an
      early indicator of ailments such as Parkinson's disease. Within the next few
      years reality mining will become more common, thanks in part to the proliferation
      and increasing sophistication of mobile phones. Many handheld devices now have
      the processing power of low-end desktop computers, and they can also collect more
      varied data, due to components such as GPS chips that track location. The Chief
      Technology Officer of EMC, a large digital storage company, estimates that this
      sort of personal sensor data will balloon from 10% of all stored information to
      90% within the next decade. While the promise of reality mining is great, the
      idea of collecting so much personal information naturally raises many questions
      about privacy. It is crucial that behavior-logging technology not be forced on
      anyone. But legal statutes are lagging behind data collection capabilities,
      making it particularly important to begin discussing how the technology will and
      should be used. Therefore, an additional focus of this chapter will be the
      development of a legal and ethical framework concerning the data used by reality
      mining techniques.

PMID- 19745475
TI  - Artificial-intelligence-based hospital-acquired infection control.
AB  - Nosocomial or hospital-acquired infections (NIs) are a frequent complication in
      hospitalized patients. The growing availability of computerized patient records
      in hospitals permits automated identification and extended monitoring for signs
      of NIs. A fuzzy- and knowledge-based system to identify and monitor NIs at
      intensive care units (ICUs) according to the European Surveillance System HELICS
      (NI definitions derived from the Centers of Disease Control and Prevention (CDC)
      criteria) was developed and put into operation at the Vienna General Hospital.
      This system, named Moni, for monitoring of nosocomial infections contains medical
      knowledge packages (MKPs) to identify and monitor various infections of the
      bloodstream, pneumonia, urinary tract infections, and central venous catheter
      associated infections. The MKPs consist of medical logic modules (MLMs) in Arden
      syntax, a medical knowledge representation scheme, whose definition is part of
      the HL7 standards. These MLM packages together with the Arden software are well
      suited to be incorporated in medical information systems such as hospital
      information or intensive-care patient data management systems, or in web-based
      applications. In terms of method, Moni contains an extended data-to-symbol
      conversion with several layers of abstraction, until the top level defining NIs
      according to HELICS is reached. All included medical concepts such as "normal",
      "increased", "decreased", or similar ones are formally modeled by fuzzy sets, and
      fuzzy logic is used to process the interpretations of the clinically observed and
      measured patient data through an inference network. The currently implemented
      cockpit surveillance connects 96 ICU beds with Moni and offers the hospital's
      infection control department a hitherto unparalleled NI infection survey.

PMID- 19745476
TI  - Innovations in connected health.
AB  - Technological advancements in recent decades have made the concept of Connected
      Health feasible. These innovations include hardware innovations (such as wearable
      medical technology), and software (such as electronic personal health record
      systems e.g., Google Health and Microsoft HealthVault). Technology innovations
      must be accompanied by process innovations to truly add value. In health care
      that includes clinical process innovations and business process innovations. This
      chapter outlines how the healthcare system is being affected by innovations in
      connected health. It provides examples that illustrate the various categories of
      innovation and their impact. Now more than ever, health care reform is required
      in the U.S. The systems outlined in this chapter will allow care that is of high
      quality, while extending providers across more patients (i.e. increasing access)
      at a lower overall cost (improved efficiency).

PMID- 19745477
TI  - Talking about painful subjects: flexibility and constraints in patient
      interviews.
AB  - Increasing understanding of how to categorize patient symptoms for efficient
      diagnosis has led to structured patient interviews and diagnostic flowcharts that
      can provide diagnostic accuracy and save valuable physician time. But the
      rigidity of predefined questions and controlled vocabulary for answers can leave
      patients feeling over-constrained, like the doctor (or computer system) is not
      really listening to them. In addition, not hearing the patient's own words can
      lead to the physician overlooking subtle details that are diagnostically
      relevant. How can we reconcile the need for patients to express themselves with
      the doctor's need to understand the patient's experience in medically appropriate
      terms? We present I'm Listening, a system for automatically conducting patient
      pre-visit interviews. It does not replace a human doctor, but can be used before
      an office visit to elicit complaint details. This information can be used to
      triage care and prepare patients for visits with educational materials and
      appropriate tests, making better use of both doctor and patient time. It uses an
      on-screen avatar and natural language processing to (partially) understand the
      patient's response. Key is a Commonsense reasoning system that lets patients
      express themselves in unconstrained natural language, even using metaphor, and
      that maps the language to medically relevant categories. For example, if a
      patient describes his or her pain like, "someone sticking in a knife and then
      turning it", the system could categorize it as sharp, intense, and localized.

PMID- 19745478
TI  - Adaptive information networks in healthcare: spontaneous interoperability.
AB  - In this paper we consider self organizing frameworks for healthcare in a model
      mimicking biologic frameworks. We support self organization via attribute based
      memory mapped information in original random form. 'Spontaneous interoperability'
      and subsequent adaptability is facilitated by the memory map which describes the
      serialized electronic ordering of transferred information, its evolutionary
      history, and meta-data associated with the information. Memory maps are
      transferred in a discovery process facilitating interoperability by means of
      application adaptation. We demonstrate the potential for network entities
      utilizing the framework to work together even though they were initially unaware
      of the potential. We recognize the challenges faced, define initial targeted
      infrastructure to aid in the advancement of adaptive networks, and suggest future
      work. The goals of adaptability in healthcare require timely access to
      information relevant to the decision process and the elimination of slow and
      costly integrations. It will allow for accurate representation, diversity,
      longevity/viability, and increased depth/ range of computable information for
      computational intelligence enhancement. Increased availability of information
      provided by an adaptive network may help to improved patient outcomes and provide
      earlier detection, prevention of disease, and a reduction in medical errors.

PMID- 19745479
TI  - Towards intelligent Internet-roaming agents for mining and inference from medical
      data.
AB  - This paper is effectively subtitled "Considerations of Requirements for
      Programmable Laws of Probabilistic Higher Order Logical Thought". Why such a
      need? Issues such as privacy, security, bandwidth, and computational power demand
      not a central analyzing agency, but roaming agents to analyze the global
      explosion of medical data in many hundreds of petabytes distributed across many
      sites. They will send back only the conclusions, not the source data. But how
      will they reach those conclusions? This future pressing need will driving workers
      to consider Best Practice in inference. Right now, there are diverse approaches
      to inference, and it is not clear how to unify them into a self-consistent
      system. For example, there is not even universal agreement on how to treat
      probabilistic higher order logic. Quantum mechanics is held by many to be a
      universal system, but produces bizarre predictions for the everyday world of
      human experience. However, by rotation of the imaginary number i = square root of
      (-1) quantum mechanics to the split complex number h such that hh = + 1, quantum
      mechanics becomes an inference system for higher order probabilistic logic. And
      the system has interesting emergent properties which may shed light on the nature
      of thought.

PMID- 19745480
TI  - Future of eHealth: can consumers cure themselves?
AB  - In the next decade e-Health, or Connected Health, based on traditional
      Information Technology (IT) will expand to include molecular communications due
      to the emergence of nano-sensors capable of monitoring the health of individual
      cells. Artificially created boundaries between medicine and IT must be removed in
      order to take advantage of the new opportunity to dramatically improve the
      precision of medical diagnosis. Human physicians and nurses who remain unaided
      will not be able to utilize the new flow of molecular data to their patients'
      full advantage. Medicine will evolve into a new discipline that could be called
      "ITicine," reflecting the ubiquitous use of caring machines by both consumers and
      health professionals to reason with and learn from petabytes of behavioral,
      physiological and molecular data. Data about our human lives collected digitally
      will increase from 10% to 90% due to physical-sensing, socio-sensing & nano
      sensing. The final goal is to allow consumers to cure themselves with the help of
      caring machines supported by omnipresent computing. The strategy for the future
      must then involve immediate and massive investment in intelligent medical
      software and adaptive networks, radical improvement of software development
      methodologies and social transition to a "machine trust" mentality, where health
      decisions can be made by computing agents and medical devices rather than doctors
      or patients. This could eliminate the error-prone features of the current
      healthcare system described by Dr. Craig Feied et al in "Indistinguishable from
      Magic: Health and Wellness in a Future of Sufficiently Advanced Technology".

PMID- 19745481
TI  - Fantastic voyage: live long enough to live forever. The science behind radical
      life extension questions and answers.
AB  - Putting an end to human aging is now becoming a reality, and immortality is no
      longer just a dream. Through what we are calling "Fantastic Voyage," we provide a
      guide to achieving life extension through various means, thereby slowing down
      aging and disease processes. The three components of Fantastic Voyage are: Bridge
      One--Aggressively applying today's knowledge. Bridge Two--Putting biotechnology,
      such as gene technologies, to use with therapeutic cloning and rejuvenation
      medicine. Bridge Three--Putting nanotechnology to use by developing a means to
      rebuild our bodies and brains with nanobots. Many of these technology solutions
      can be simulated today through the use of targeted supplements, designed to
      address the specific needs of an individual, such as insulin resistance,
      cholesterol and homocysteine levels, and inflammation. To slow aging now, we
      propose a program of supplementing aggressively, eating foods that impede aging
      and disease processes, and reversing inflammation through diet. We also provide
      guidance to customize each program to the specific needs of the individual.
      Emerging technologies in rational drug design, tissue engineering, gene therapy,
      and nanobots (among others) promise a future of automated life extension. The use
      of such technologies, and the resulting dramatic increases in productivity in all
      areas of human endeavor, will enable us to live in a world in which all our
      physical needs can be met.

PMID- 19745482
TI  - The singularity and the Methuselarity: similarities and differences.
AB  - Aging, being a composite of innumerable types of molecular and cellular decay,
      will be defeated incrementally. I have for some time predicted that this
      succession of advances will feature a threshold, which I here christen the
      "Methuselarity," following which there will actually be a progressive decline in
      the rate of improvement in our anti-aging technology that is required to prevent
      a rise in our risk of death from age-related causes as we become chronologically
      older. Various commentators have observed the similarity of this prediction to
      that made by Good, Vinge, Kurzweil and others concerning technology in general
      (and, in particular, computer technology), which they have termed the
      "singularity." In this essay I compare and contrast these two concepts.

PMID- 19745483
TI  - Of mice and men.
AB  - In this chapter we consider a distinct example of the link between biology and
      technology, with particular reference to the brain. We look at the example of a
      brain cultured in the laboratory which is then linked to a physical robot body.
      The overall entity therefore consists of a physical robot body controlled by a
      purely biological brain. The entire system provides a wonderful base for the
      study of the fundamental features of diseases such as strokes and Alzheimer's
      disease, as well as allowing for a basic investigation into the mechanisms for
      neural signal transfer.

PMID- 19745484
TI  - Future approaches to organ regeneration: microscale environments, stem cell
      engineering, and self-assembly of living tissues.
AB  - A promising means to address the limited supply of donor tissue is through the
      generation of artificial organs consisting of cells and materials. Progress
      towards this goal is limited by three main obstacles namely the generation of a
      sufficient number of cells specific to the organ, the arrangement of these cells
      in a functional tissue architecture and the delivery of nutrients and removal of
      waste from the tissue mass. This chapter describes the emerging approaches that
      may be achieved by the control of stem cell differentiation, control of the local
      tissue environment on the microscale, and the generation of complex structures
      containing multiple cell types.

PMID- 19745485
TI  - Links between quantum physics and thought.
AB  - Quantum mechanics (QM) provides a variety of ideas that can assist in developing
      Artificial Intelligence for healthcare, and opens the possibility of developing a
      unified system of Best Practice for inference that will embrace both QM and
      classical inference. Of particular interest is inference in the hyperbolic
      complex plane, the counterpart of the normal i-complex plane of basic QM. There
      are two reasons. First, QM appears to rotate from i-complex Hilbert space to
      hyperbolic-complex descriptions when observations are made on wave functions as
      particles, yielding classical results, and classical laws of probability
      manipulation (e.g. the law of composition of probabilities) then hold, whereas in
      the i-complex plane they do not. Second, i-complex Hilbert space is not the whole
      story in physics. Hyperbolic complex planes arise in extension from the Dirac
      Clifford calculus to particle physics, in relativistic correction thereby, and in
      regard to spinors and twisters. Generalization of these forms resemble
      grammatical constructions and promote the idea that probability-weighted
      algebraic elements can be used to hold dimensions of syntactic and semantic
      meaning. It is also starting to look as though when a solution is reached by an
      inference system in the hyperbolic-complex, the hyperbolic-imaginary values
      disappear, while conversely hyperbolic-imaginary values are associated with the
      un-queried state of a system and goal seeking behavior.

PMID- 19745486
TI  - Welcome to the future of medicine.
AB  - This chapter describes the negative consequences of medical technology
      development and commercialization that is too slow, and makes the case for an
      immediate large scale investment in medical nanorobots to save 52 million lives a
      year. It also explains the essence of nanotechnology, its life-saving
      applications, the engineering challenges, and the possibility of 1000-fold
      improvement over our current human biological abilities. Every decade that we
      delay development and commercialization of medical nanorobotics, half a billion
      people perish who could have been saved.

PMID- 19745487
TI  - Medical applications of nanoparticles and nanomaterials.
AB  - Current clinical diagnostics and therapeutics platforms are often limited by
      borderline sensitivity or efficacy levels. These limitations result from low or
      minimal specificity for the intended target cell or organ, span a multitude of
      physiological disorders and result in nominal success rates for diagnosis or
      treatment in many cases. Diagnosis and treatment of diseases such as cancer or
      viral infections require next generation medical methods. Nanotechnology has the
      potential to significantly address diagnostics and therapeutics sensitivity and
      resulting unwanted side effects by providing extremely precise reagents and tools
      that allow for unparalleled detection and treatment at the clinical level. This
      is accomplished through extremely controlled nanofabrication methodologies which
      result in the generation of molecularly defined nanoscale materials and devices
      that harbor known physical properties unique to each material in question and
      useful for particular medical applications. The further precise targeting of
      these materials to specific sites within the body allows for an added layer of
      accuracy and potency. Research in this area is quickly advancing to the point of
      providing a comprehensive portfolio of nanotechnology-based diagnostic and
      therapeutic platforms that will be unparalleled in sensitivity, specificity and
      elimination of unwanted side effects.

PMID- 19745488
TI  - Diamond bio electronics.
AB  - The use of diamond for advanced applications has been the dream of mankind for
      centuries. Until recently this dream has been realized only in the use of diamond
      for gemstones and abrasive applications where tons of diamonds are used on an
      annual basis. Diamond is the material system of choice for many applications, but
      its use has historically been limited due to the small size, high cost, and
      inconsistent (and typically poor) quality of available diamond materials until
      recently. The recent development of high quality, single crystal diamond crystal
      growth via the Chemical Vapor Deposition (CVD) process has allowed physcists and
      increasingly scientists in the life science area to think beyond these
      limitations and envision how diamond may be used in advanced applications ranging
      from quantum computing, to power generation and molecular imaging, and eventually
      even diamond nano-bots. Because of diamond's unique properties as a bio
      compatible material, better understanding of diamond's quantum effects and a
      convergence of mass production, semiconductor-like fabrication process, diamond
      now promises a unique and powerful key to the realization of the bio-electronic
      devices being envisioned for the new era of medical science. The combination of
      robust in-the-body diamond based sensors, coupled with smart bio-functionalized
      diamond devices may lead to diamond being the platform of choice for bio
      electronics. This generation of diamond based bio-electronic devices would
      contribute substantially to ushering in a paradigm shift for medical science,
      leading to vastly improved patient diagnosis, decrease of drug development costs
      and risks, and improved effectiveness of drug delivery and gene therapy programs
      through better timed and more customized solutions.

PMID- 19745489
TI  - Diagnostics for a personalized medical future: extending our senses to the
      molecular scale.
AB  - Unprecedented advances in our understanding of the molecular world around us and
      within us have the potential to drive a revolution in health care. A key aspect
      of bringing this revolution to fruition is streamlining and simplifying our
      ability to detect and quantify molecules of biomedical relevance. New "sample in-
      answer out" diagnostic systems, some with the potential to detect even single
      viruses or single copies of molecules, are under development in many academic and
      industrial laboratories worldwide. This chapter discusses our efforts at the
      University of Rochester towards the development of three complementary molecular
      detection systems, with applications from allergy diagnosis to monitoring
      infectious disease.

PMID- 19745490
TI  - Maintaining your health from within: controls for nanorobot swarms in fluids.
AB  - Molecular electronics and nanoscale chemical sensors could enable the
      construction of microscopic sensors capable of detecting patterns of chemicals as
      they flow passively in a fluid. Information from a large number of such devices
      allow the estimation of properties of tiny chemical sources in a macroscopic
      tissue volume. Although such devices cannot yet be fabricated, estimates of
      plausible device capabilities in small blood vessels allow the evaluation of
      their performance for typical chemicals released by tissues in response to
      localized injury or infection. The devices can readily discriminate a single cell
      sized chemical source from the background chemical concentration, providing high
      resolution sensing in both time and space. By contrast, such a chemical source
      would be difficult to distinguish from background when diluted throughout the
      blood volume as obtained with a blood sample. These microscopic, programmable
      devices could also aid treatments, such as precisely targeting drug delivery and
      improving speed and accuracy of microsurgery.

PMID- 19745491
TI  - Fight for chromallocyte.
AB  - This paper reports on the most important recent technological event and its
      significance to the human race: chromallocyte designed by Robert Freitas--a
      nanorobot that would be capable of replacing chromosomes on a cell by cell basis
      throughout the body in vivo. The significance of chromallocyte comes from its
      ability to painlessly reverse the effects of genetic disease and other
      accumulated damage to our genes thus preventing aging. It could reduce suffering,
      save lives and enhance human potential. By analogy to the successful effort to
      put man on the moon, we should aim at chromallocyte landing on the liver by 2039
      which would commemorate 70th anniversary of man landing on the Moon. The same
      strategic planning principle could be applied. We should have a dream with a
      deadline of 2039.

PMID- 19745492
TI  - RAGE Control: Regulate and Gain Emotional Control.
AB  - Advances in neurobiology and computer science make possible interventions
      designed to strengthen basic processes behind emotional control. We present one
      such computer-based intervention, RAGE Control (Regulate And Gain Emotional
      Control). This extends the usual paradigm of biofeedback by requiring relaxation
      in the midst of engaging executive processes in a quick reaction task. RAGE
      Control teaches children to simultaneously focus, react, inhibit impulses, and
      keep their heart rate down in the context of a traditional space battle game. The
      program is grounded in the theory of Cognitive Behavioral Therapy and is
      currently in clinical use by psychotherapists at Children's Hospital in Boston.
      It aims to reduce the need for psychotropic medication to help children gain
      emotional control. Clinical trials to test the promise of this technology are
      warranted.

PMID- 19745493
TI  - Therapeutic robotics for children with disabilities: a case study.
AB  - The advancement of technology is having a profound effect on enhancing the lives
      of children with disabilities. As advances in biomedical technology allow
      research breakthroughs to continue at a steady pace, more and more is being
      discovered about the nature of different disorders in children. At the same time,
      partly due to the continuing rapid rate of advancement (and societal acceptance)
      of robotics technology, researchers, educators, and therapists are exploring the
      idea that robots might be used as an effective therapeutic and educational tool.
      Over the past nine years, AnthroTronix has collaborated extensively with
      therapists, educators, researchers, parents, and children to uncover the
      therapeutic and educational benefits of including robotics as part of
      rehabilitation curriculum for children. As a central part of this effort, the
      company has worked with its colleagues to develop and refine the CosmoBot system,
      an interactive robotic toolkit designed to enhance therapy, education, and play
      for children with disabilities.

PMID- 19745494
TI  - Sound of a hug.
AB  - Currently all diagnosis of autism is based entirely on behavioral measures. A
      theory put forward by the author suggests a way toward development of a purely
      empirical objective diagnostic tool. Focusing on hearing, the most social of the
      senses and specifically on the intriguing, yet seemingly unrelated phenomena of
      Otoacoustic Emissions (OAE) and Attention Shift Delay (ASD), the author suggests
      a framework for research on the measurement of OAE that may lead to the
      development of just such a diagnostic tool. Byproducts of the research already
      include a patented hearing aid add-on for helping speech in background babble
      discrimination and an advanced wearable calming device that promises to improve
      the quality of life not only for people with autism, but many others who find
      themselves troubled by stress.

PMID- 19745495
TI  - Haptic medicine.
AB  - The paper introduces haptic medicine--healthcare based on loving touch for
      healing and preventing disease. We describe the effects of loving touch (a square
      inch of our skin has over 1000 nerves) on the body, brain and mind. We describe
      two web-based health education and media projects. The first, HYPERLINK
      "http://www.21stcenturymed.org" www.21stcenturymed.org is a place for health
      practitioners to start learning about touch and resources. The second project,
      Humans Without Borders, is a multi-lingual self help education website for
      everyday people. Teaching materials for these projects are based on our previous
      work with a form of haptic medicine known as psychophysiophilosophy with patients
      at Stanford Hospital, Kaiser Permanente and Lucille Packard Children's Hospital.
      We describe psychophysiophilosophy, relate motherly love to recent discoveries in
      neurosciences and give hints on ways to increase motherly love in each of us. We
      present a plan for moving into the future by re-introducing haptic medicine into
      our daily lives through self-help and as an adjunct for current physician
      practice. There is an exercise in self-help for the reader and an appendix of
      recent clinical research with profound benefits on the use of human touch for
      over 40 conditions.

PMID- 19745496
TI  - Future of obesity prevention and treatment.
AB  - The prevalence of obesity has risen sharply during the last 4 decades imposing a
      serious health burden to modern society. Obesity is known to cause and exacerbate
      many chronic diseases such as diabetes, hypertension, dyslipidemia, coronary
      heart disease, stroke, obstructive sleep apnea and certain cancers, among many
      others. The rise in obesity prevalence is mainly caused by overconsumption of
      energy, coupled to a sedentary life in susceptible individuals. Weight
      homeostasis is paramount for survival and its control is coordinated by neural
      and endocrine signals emanating from the fat tissue, digestive system and brain.
      During thousands of years humans were challenged by nutrient deprivation,
      developing an efficient mechanism to store energy. It explains the difficulty in
      losing weight, making obesity prevention the main effective health approach to
      halt the obesity epidemic.

PMID- 19745498
TI  - A practice for all seasons: male circumcision and the prevention of HIV
      transmission.
AB  - HIV/AIDS as a global epidemic has exerted its terrifying influence for quite some
      time now. Currently, a vaccine for its prevention appears to be near impossible.
      HIV has spread across the globe without deference to gender, race, religion, or
      socioeconomic status. Despite a growth in HIV awareness and interventions, there
      are perplexingly different prevelence rates in different countries with seemingly
      similar behavioral patterns. In this review we examined these variances in
      infection rates and found conclusive evidence that male circumcision makes a
      major difference. Removal of the foreskin of the penis (male circumcision, MC, C)
      is known to significantly reduce female-to-male HIV transmission through sex,
      which then decreases male-to-female transmission. Three recent randomized
      controlled studies from Africa have shown that circumcision offers a 60% to 70%
      protective effect against heterosexual acquisition of HIV. The protective effect
      of circumcision against HIV, known since the 1980s, has been confirmed by more
      than 30 studies before these three famous randomized controlled trials, which are
      the criterion standard of clinical research. The global epidemiology data clearly
      indicates a reduction of over 99.9% in HIV prevalence in countries where C rate
      is over 80%. As we show in this review, MC not only reduces HIV but also other
      sexually transmitted diseases (STDs). Circumcision's decisive role in reducing
      the effect of HIV transmission has been so convincing that it has now been
      accepted officially by the WHO, UN, and NIH. Moreover, many nations have
      initiated adult circumcision as a public health measure.

PMID- 19745499
TI  - Control of meningococcal meningitis outbreaks in sub-Saharan Africa.
AB  - Outbreaks of Neisseria meningitidis recur frequently in the African Sahel where
      they are responsible for high mortality and morbidity, especially in children. An
      effective vaccine has been in existence for more than 30 years, but despite this,
      the control of epidemics has failed. Moreover, the geographical distribution of
      N. meningitidis seems to be increasing, perhaps because of climate change but
      also because of the economic crisis which prevails throughout much of Africa
      leading to population movements and the breakdown of essential services. Although
      alarming, the emergence of new serogroups in recent epidemics (such as serogroups
      X and W135) should not mask the fact that serogroup A remains the most common
      meningococcal isolate from meningitis cases and is therefore the most significant
      target for control. The development of a low-cost conjugate meningococcal vaccine
      should support a strategy of preventive immunization, as this strategy is one
      that appears most effective to control this plague.

PMID- 19745500
TI  - Helicobacter pylori, a causative agent of vitamin B12 deficiency.
AB  - BACKGROUND: Helicobacter pylori is one of the most common causes of peptic ulcer
      disease worldwide and a major cause of chronic superficial gastritis leading to
      atrophy of gastric glands. METHODOLOGY: A total of 60 patients suffering from
      gastric disease due to H. pylori infection were evaluated. Endoscopy was
      performed and gastric biopsies were obtained for histopathology and urease test.
      Blood was simultaneously collected for the determination of the levels of vitamin
      B12 and the MCV. Vitamin B12 levels were determined by chemiluminescent assay.
      RESULTS: Our results indicate that the mean vitamin B12 level +/- SEM for the
      total population, the H.pylori infected and non-infected patients were 264.5+/
      22.9, 207.7+/-21.9 and 419.7+/-39.8 respectively. H. pylori was found in 71.7%
      (43/60) of the patients tested. The level of vitamin B12 was lower than 200pg/ml
      (deficient) in 67.4% (29/43) of patients tested positive for H. pylori.
      CONCLUSION: H. pylori appears to be implicated in causing vitamin B12 deficiency.

PMID- 19745501
TI  - High resistance prevalence towards ampicillin, co-trimoxazole and ciprofloxacin,
      among uropathogenic Escherichia coli isolates in Mexico City.
AB  - BACKGROUND: The prevalence of antimicrobial resistance among uropathogenic E.
      coli varies widely worldwide; to guide empirical therapy is necessary to have
      local, up-to-date susceptibility data. METHODOLOGY: We tested 907 isolates from
      patients in Mexico City by disk diffusion and further characterized
      ciprofloxacin, cephalosporin and nitrofurantoin resistant strains. RESULTS:
      Isolates were mostly resistant to ampicillin (74%), trimethoprim-sulfamethoxazole
      (60.1%) and ciprofloxacin (32.6%). The most effective drug was netilmicin (5.1%
      resistant) and the most effective of oral drugs was nitrofurantoin (7.4%
      resistant). Sixty-percent of ciprofloxacin-resistant strains had minimal
      inhibitory concentrations of 125 microg/ml or higher, well beyond urinary
      concentrations at the end of the 12-hour inter-dose period for standard oral
      regimes. Extended-spectrum beta-lactamases were detected in 6% of strains, most
      of them from community-acquired infections. All strains resistant to
      nitrofurantoin carried a 20 Kb plasmid, which when transformed into a susceptible
      recipient, conferred resistance to nitrofurantoin, ampicillin, sulfonamides,
      streptomycin, and partially protected against ciprofloxacin. CONCLUSIONS: Drugs
      considered of choice against uncomplicated urinary tract infections are facing
      high resistance prevalences and resistance determinants formerly seen only at
      hospitals are now among community strains. Treatment guidelines from developed
      countries might not reflect these local trends.

PMID- 19745502
TI  - Antibiotic resistance in pathogens causing community-acquired urinary tract
      infections in India: a multicenter study.
AB  - BACKGROUND: Empiric treatment of community-acquired urinary tract infections (CA
      UTI) is determined by the antibiotic sensitivity patterns of uropathogens in a
      population. This study was conducted to determine patterns of resistance amongst
      CA-uropathogens in India, to help establish local guidelines on treatment of CA
      UTI. METHODOLOGY: 531 consecutive positive urine cultures taken from adult non
      pregnant females attending outpatient clinics of five hospitals in Delhi, India,
      were analysed. Sensitivity testing was done for ciprofloxacin, trimethoprim
      sulphamethoxazole (SXT), amoxicillin, amoxicillin-clavulanate, amikacin,
      nitrofurantoin, piperacillin-tazobactam and meropenem in each isolate. RESULTS:
      E. coli comprised 68%; Klebsiella 16.9%; Proteus 5.5%; Enterobacter 5.3%;
      Staphylococcus saprophyticus 2.8%; and others 1.5% of the isolates. Furthermore,
      26.9% of the gram negative isolates were ESBL producers. Antibiotic sensitivity
      of all the gram negative organisms showed that 35.8% were sensitive to
      ciprofloxacin; 30% to SXT; 17.7% to amoxicillin; 41.6% to
      amoxicillin/clavulanate; 75.6% to amikacin; 65.7% to nitrofurantoin; 90.2% to
      piperacillin-tazobactam; and 100% to meropenem. CONCLUSION: High levels of ESBL
      producers among gram negative CA-uropathogens was seen in our country. This,
      along with the alarming rate of resistance to ciprofloxacin, SXT and amoxicillin,
      precludes the use of these commonly used antibiotics for empiric treatment of CA
      UTI in India.

PMID- 19745503
TI  - Evaluation of febrile neutropenic attacks in a tertiary care medical center in
      Turkey.
AB  - BACKGROUND: Infectious complications in febrile neutropenic patients are still
      major causes of morbidity and mortality despite significant advances in
      diagnostic techniques and antimicrobial therapy. In this study, we describe the
      characteristics of patients with hematological malignancies who were evaluated
      for suspected infection. This study was also conducted to assess the isolation
      rate of bacterial and fungal causative agents in febrile neutropenic attacks.
      METHOD: The study was conducted at Pamukkale University Hospital, Turkey. In
      order to identify the characteristics of patients with hematological malignancies
      in the presence/suspicion of any accompanying infectious disease, patients'
      charts with hematological malignancies were reviewed for signs/symptoms of any
      infection between October 1, 2001, and May 31, 2005, retrospectively. RESULTS:
      Overall, 90 infectious episodes occurred in 59 patients. The most common
      underlying diseases were acute myelogenous leukemia (61.0%) and acute lymphocytic
      leukemia (15.3%). The absolute neutrophil count was lower than 100/mm(3) in 33
      (36.7%) episodes. Microbiologically and clinically documented infections and
      fever of unknown origin were observed in 35.6%, 28.9%, and 35.6% of the
      participants, respectively. Bloodstream infections and pneumonia were detected in
      21.1% and 18.9% of episodes, respectively. Gram negative organisms were most
      common (58.4%), followed by gram positive cocci. A combination of third
      generation cephalosporin and an aminoglycoside were used in 44.4% of episodes
      initially. Fever resolved in 24.4% of episodes using the initial therapy. The
      mortality rate was 15.6%. CONCLUSION: These results showed that infections with
      gram-negative bacteria continue to predominate in febrile neutopenic episodes in
      our center.

PMID- 19745504
TI  - Baseline assessment of intensive care-acquired nosocomial infection
      surveillancein three adult intensive care units in Malaysia.
AB  - BACKGROUND: Nosocomial infections (NIs) have a serious impact on patient outcomes
      in Intensive Care Units (ICUs). METHOD: A prospective cohort-targeted
      comprehensive surveillance study on NI associated with usage of devices was
      conducted in three ICUs in Malaysia using a developed NI surveillance form.
      Patients who developed infection outside an ICU were excluded from the study.
      RESULTS: The device associated NI was 21.1%. The mean duration for development of
      NI was 10.0 +/- 7.44 days in ICU. The major device-associated infections were
      nosocomial pneumonia (18.7%) followed by bacteremia (8.5%) and urinary tract
      infections (4.7%) respectively. NI incidence density rate was 20.6 per 1,000
      patient-days. Bacteremia, urinary tract infection (UTI) and nosocomial pneumonia
      (NP) rates were 8.9, 4.7 and 20.5 per 1,000 patient-days, respectively.
      Acinetobacter species, Klebseilla pneumoniae, Pseudomonas aeruginosa and
      Methicillin-resistant Staphylococcus aureus were the predominant pathogens
      isolated from the NIs subjects during the study period in the three ICUs.
      CONCLUSION: Analysis of the rate of the NIs associated with usage of devices in
      the three ICUs showed that it is highly correlated with the use of mechanical
      ventilation devices, followed by intravascular devices and usage of indwelling
      urinary catheters.

PMID- 19745505
TI  - Prevalence and determinants of nonadherence to highly active antiretroviral
      therapy among people living with HIV/AIDS in Ibadan, Nigeria.
AB  - OBJECTIVE: To determine the level of nonadherence to highly active antiretroviral
      therapy (HAART) and to explore the association of factors militating against
      adherence and nonadherence to therapy among people living with HIV/AIDS (PLWHA)
      at an Antiretroviral Clinic in Ibadan, Nigeria. DESIGN: A cross-sectional survey
      was employed to determine the prevalence of nonadherence. METHODOLOGY: A
      structured interviewer-administered questionnaire was applied to consecutive
      PLWHA who had been on therapy for a minimum of three months. The completed
      questionnaires were entered into a computer and analyzed. Multivariate logistic
      regression was used to determine factors associated with nonadherence. RESULTS:
      Three hundred and eighteen people living with HIV/AIDS completed the
      questionnaire. Their mean age was 39.1+/-9.6 years. There were 173 (54.4%)
      females and 145 (45.6%) males. The median duration on HAART was 19 months (Range
      3 to 28 months) and the prevalence of nonadherence was 118 (37.1%) using the less
      than 95% adherence profile. About a third (31.5%) of those missing therapy
      reportedly missed their medication because of fasting. Multiple logistic
      regression analysis revealed that patients who felt healthy or simply forgot to
      take their drugs and those not willing to disclose their HIV status were
      independently, significantly associated with less than 95% adherence. CONCLUSION:
      The study showed that nonadherence to HAART is a problem in the ARV clinic and
      that the feeling of being healthy, forgetfulness, and unwillingness to disclose
      HIV status by PLWHA were significant barriers to adherence. Efforts to improve
      adherence in the clinic will have to address these issues among others.

PMID- 19745506
TI  - Prevalence of Hepatitis B virus genotype D in females in Karachi, Pakistan.
AB  - BACKGROUND: Hepatitis B virus (HBV) is an etiological agent of acute and chronic
      liver disease existing throughout the world. The high genetic variability of HBV
      genome is reflected by eight genotypes (A to H), and each genotype has
      characteristic geographical distribution, which is important epidemiologically.
      Previous studies from the province of Sindh, Pakistan, have reported that
      genotypes A and D as prevalent HBV genotypes. The aim of the study was to
      investigate the prevalence of HBV genotypes in physically healthy females at two
      universities in Karachi, Sindh, Pakistan. METHODOLOGY: Blood was collected from a
      total of 4,000 healthy female volunteer students and serum samples obtained were
      screened for Hepatitis B surface antigen (HBsAg), and anti-HBs antibodies by
      immunochromatography and ELISA. Genotyping was conducted for 6 HBV genotypes (A
      through F). Both genotyping and sequencing data of HBV positive females are
      described. RESULTS: Out of 4,000 volunteers, 180 (4.5%) tested positive for HBsAg
      and 20 (0.5%) were positive for HBs antibodies. All 180 serum samples were
      genotyped by PCR and sequencing analyses was conducted for 21 samples. Out of 180
      HBsAg positive samples, 150 showed a single HBV D genotype infection; 29 showed
      co-infection of genotypes B and D; and 1 exhibited co-infection of genotypes C
      and D. Twenty-one representative samples were selected randomly from genotypes B,
      D, and C for sequencing and each isolate clustered with respective reference
      genotype sequence, thus validating the genotyping strategy. CONCLUSION: Genotype
      D appears to be the dominant genotype prevalent in Karachi's otherwise healthy
      female population.

PMID- 19745507
TI  - Moringa oleifera leaf extracts inhibit 6beta-hydroxylation of testosterone by
      CYP3A4.
AB  - BACKGROUND: Moringa oleifera is a tropical tree often used as a herbal medicine,
      including by people who test positive for HIV. Since herbal constituents may
      interact with drugs via inhibition of metabolizing enzymes, we investigated the
      effects of extracts of M. oleifera on the CYP3A4-mediated 6beta-hydroxylation of
      testosterone. METHODS: Methanolic and aqueous leaf and root of extracts of M.
      oleifera with concentrations between 0.01 and 10 mg/ml were incubated with
      testosterone and mixed-sex human liver microsomes in the presence of NADPH.
      Metabolite concentrations were determined by HPLC. The cytotoxicity of the
      extracts was tested with HepG2 cells using the MTT formazan assay. RESULTS:
      Significant CYP3A4 inhibitory effects were found, with IC50 values of 0.5 and 2.5
      mg/ml for leaf-methanol and leaf-water extracts, respectively. Root extracts were
      less active. Cytotoxicity was observed only with the leaf-water extract (IC50 = 6
      mg/ml). CONCLUSIONS: Further investigation is warranted to elucidate the
      potential of M. oleifera for clinically significant interactions with
      antiretroviral and other drugs.

PMID- 19745508
TI  - Diagnostic efficacy of Brucella abortus strain RB51 in experimentally inoculated
      Sprague-Dawley rats using western blot assay.
AB  - BACKGROUND: To investigate the diagnosis and efficacy of Brucella abortus strain
      RB51 (SRB51) in experimentally inoculated Sprague-Dawley (SD) rat using western
      blot assay. METHODOLOGY: Female SD rats were orally administered with 1.0 x 10(7)
      colony forming unit (cfu) suspension of SRB51 and half of these SD rats were
      challenged at 4 weeks post inoculation with 1.0 x 10(9) cfu suspension of B.
      abortus biotype 1 isolated in South Korea. Sera of SD rats were monitored at
      regular intervals by western blot assay using whole cell antigen of B. abortus
      strain 1119-3 (S1119-3). The bacteriological examination of blood and clinical
      examination of the rats were also performed. RESULTS: There were several bands at
      120, 70, 45, 30, 20 kDa and clear specific bands were found after vaccination
      (20, 70 kDa) and challenge (15, 20, 45, 70, 120 kDa). The highest immune response
      was observed in sera 4 weeks post SRB51 vaccination. SRB51 was recovered from the
      blood of all of SRB51 inoculated rats until one week post vaccination and there
      were no clinical signs in that inoculated rats. CONCLUSIONS: It is concluded that
      the SRB51 elicits antigen specific immunity in SD rats based on western blot
      assay.

PMID- 19745509
TI  - Occurrence of Escherichia coli O157:H7 in retail raw meat products in Ethiopia.
AB  - BACKGROUND: Escherichia coli O157:H7 (E. coli O157:H7) is now recognized as a
      major cause of diarrhoea, hemorrhagic colitis and hemolytic-uremic syndrome
      worldwide. Consumption of raw or undercooked meat of bovine origin has been the
      most common means of transmitting this organism. METHODOLOGY: Over a period of 7
      months (October 2006 to April 2007), a total of 738 raw meat samples were
      collected from bovines (n= 250), sheep (n=243) and goat (n=245) and investigated
      for the presence of E. coli O157: H7. Antimicrobial susceptibility testing was
      performed using the disk diffusion method. RESULTS: E. coli O157:H7 were isolated
      from 31 (4.2%) out of 738 meat samples examined. Among meat samples examined, the
      highest prevalence (8%) was recorded in beef, followed by lamb and mutton (2.5%)
      and goat meat (2%). The isolated strains were found to be susceptible (100%) to
      amikacin, chloramphenicol, gentamicin, kanamycin, nalidixic acid, norfloxacin,
      polymyxin B and trimethoprim-sulfamethoxazole. Multidrug resistance to three or
      more drugs was detected in 7/31 (22.6%) strains. CONCLUSIONS: The results of this
      study revealed the presence of E. coli O157:H7 in retail raw meats reaching
      consumers, indicating possible risks of infection to people through the
      consumption of raw/under-cooked meat or cross-contamination of other food
      products. Coordinated actions are needed to reduce or eliminate the risks posed
      by this organism at various stages in food chain. Multiple drug resistant
      isolates detected in the present study may pose a threat to humans and further
      limit therapeutic options.

PMID- 19745510
TI  - Splenic abscess due to brucellosis.
AB  - Splenic abscess due to Brucella spp. is extremely rare. We report a case of a
      splenic abscess due to Brucella spp. in a 61-year-old male patient. Brucella
      slide and tube agglutination tests (Wright) were positive while blood culture and
      culture from splenic tissue yielded negative results. The abdominal
      ultrasonography revealed a hypoechoic intrasplenic mass 15x12 mm in diameter at
      the middle portion of the spleen. The splenic lesions disappeared after prolonged
      treatment for 7 months with a combination of doxycycline, and rifampicin,
      followed by TMP-SXT. Brucella spp. should be considered in the differential
      diagnosis of splenic abscess in countries where brucellosis is endemic. The
      results of this case and literature review shows that a conservative approach
      using optimum antibiotics alone without surgical intervention can be successful
      in the treatment of patients with splenic brucellosis.

PMID- 19745511
TI  - Extraintestinal Vibrio infections in Mauritius.
AB  - Few extraintestinal Vibrio infections have been reported in the African region.
      We report 3 cases from Mauritius: one case of Vibrio alginolyticus otitis
      externa; one case of soft tissue infection caused by non-O1 Vibrio cholerae and
      Vibrio parahaemolyticus; and one fatal case of non-O1 V. cholerae cellulitis and
      septicaemia.

PMID- 19745512
TI  - A case report of pulmonary amoebiasis with Entamoeba histolytica diagnosed in
      western Romania.
AB  - BACKGROUND: Among parasitic diseases, amoebiasis is the third most frequent cause
      of mortality after malaria and schistosomiasis. Pulmonary amoebiasis, the second
      most common extraintestinal manifestation of infection, occurs in 2%-3% of
      patients with invasive amoebiasis. The present clinical report aims to present a
      single case of a rare diagnosed parasitic disease in Romania and to emphasize the
      difficulties encounted while attempting to establish the correct diagnosis and to
      completely cure the patient. METHODOLOGY: Retrospective analysis of all medical
      records of a patient hospitalized at Victor Babes Hospital of Infectious Diseases
      in Timisoara, Romania, and diagnosed with pulmonary amoebiasis. RESULTS AND
      CONCLUSIONS: The disease debuted in 1996 with intestinal symptomatology and was
      not diagnosed at that time. Thus evolution continued for another five years
      ending with the invasion of the lung. Differential diagnosis with a bacterial
      abscess, tuberculous abscess, and neoplastic disease were considered. A routine
      microscopic examination of the sputum finally clarified the diagnosis during a
      second hospitalization pointing out the importance of collaboration between the
      infectious disease clinicians and parasitologists.

PMID- 19745513
TI  - Atypical forms of Cryptococcus neoformans in CSF of an AIDS patient.
AB  - The microscopic recognition of typical rounded capsulated yeasts in centrifuged
      cerebrospinal fluid (CSF), stained with India ink, is a common, rapid and
      effective method for the diagnosis of cryptococcal meningitis among AIDS
      patients. The presence of atypical forms of Cryptococcus neoformans var.
      neoformans in samples of CSF of an AIDS patient with cryptococcosis treated at
      the University Hospital of Infectious Disease is presented. The India ink
      microscopy of three consecutive CSF samples revealed capsulated yeast with India
      ink particles in the deteriorated capsules and capsulated pseudohyophae.
      Clinically, the patient showed a subacute meningoencephalitis, with a clinical
      picture not particularly different from those commonly observed in patients with
      AIDS-associated cryptococcosis treated in our hospital. In all cases, the culture
      of the CSF showed colonies of C. neoformans with typical macro and
      micromorphology, and the in vitro susceptibility tests to amphotericin B,
      fluocitosine, itraconazole and fluconazole showed MIC values into the limits of
      sensitivity. The presence of atypical forms of C. neoformans, considered as an
      atypical finding, could be the consequence of an adaptive phenomenon of this
      fungal species to an impaired immunological status present in the host.

PMID- 19745514
TI  - Optimization of human cytomegalovirus LightCycler real-time PCR.
AB  - BACKGROUND: Real-time PCR has been widely considered as a powerful tool for the
      evaluation of Human Cytomegalovirus (CMV) DNA kinetics. Successful PCR relies on
      optimization, which is an extremely demanding procedure. Nevertheless, certain
      values could be optimal for most primers in use. METHODOLOGY: Seventeen CMV
      primer sets recommended in the literature were selected for optimization in terms
      of MgCl2 and primers concentrations as well as annealing temperature using the
      LightCycler instrument and SYBR Green I detection format. Optimal values were
      considered as those showing the lowest crossing point (Cp), the highest
      fluorescence intensity, the steepest sigmoid curve slope, and the absence of non
      specific PCR products. RESULTS: Optimal values for most studied primers were
      found to be 3 mM for MgCl2 concentration, 0.5 microM and 0.6 microM for primers
      concentration, and 55 degrees C for annealing temperature. CONCLUSION: Adopting
      the resulting values for CMV-specific primers generally used in single-target
      real-time PCR assays with the same thermal cycler may guarantee their efficient
      performance minimizing cost and time needed for optimization.

PMID- 19745515
TI  - Typhoid fever research in developing countries.

PMID- 19745516
TI  - Regulation of Vi capsular polysaccharide synthesis in Salmonella enterica
      serotype Typhi.
AB  - The synthesis of Vi polysaccharide, a major virulence determinant in Salmonella
      enterica serotype Typhi (S. Typhi), is under the control of two regulatory
      systems, ompR-envZ and rscB-rscC, which respond to changes in osmolarity. Some S.
      Typhi isolates exhibit over-expression of Vi polysaccharide, which masks clinical
      detection of LPS O-antigen. This variation in Vi polysaccharide and O-antigen
      display (VW variation) has been observed since the initial studies of S. Typhi.
      We have reported that the status of the rpoS gene is responsible for this
      phenomenon. We review the regulatory network of the Vi polysaccharide, linking
      osmolarity and RpoS expression. Also, we discuss how this may impact live
      attenuated Salmonella vaccine development.

PMID- 19745517
TI  - The laboratory diagnosis of enteric fever.
AB  - The diagnosis of enteric fever currently depends upon the isolation of Salmonella
      from a patient, most commonly by blood culture. This facility is not available in
      many areas where the disease is endemic. Serodiagnosis depends upon the 100-year
      old Widal test, and other serological diagnostic tools have limitations because
      of their low sensitivity and/or specificity. The most promising recently
      published results are from PCR-based amplification of DNA from the blood of
      enteric fever patients but again this technique is not available where it is most
      needed. Antigen detection has not been investigated for well over three decades
      and detecting an immune response specific for typhoid fever has been done only
      with antibody detection. There is an urgent need for the rational design and
      evaluation of effective and appropriate diagnostics for enteric fever which must
      include the emerging threat of S. Paratyphi A.

PMID- 19745518
TI  - Treatment of enteric fever.
AB  - Enteric fever is systemic illness caused by Salmonella Typhi and Salmonella
      Paratyphi A, B and C. It is believed to be a readily treatable illness by many
      clinicians in the developing world where it is endemic; however, with the
      emergence of drug resistance to fluoroquinolones, treatment is becoming
      increasingly difficult. While drugs such as cefixime, previously believed to be
      effective, have been proven otherwise, new agents such as gatifloxacin and
      azithromycin have proven to be promising. Re-emergence of chloramphenicol
      sensitive strains in previously resistant areas points towards the concept of
      antibiotic recycling, preserving the use of older antibiotics. Antibiotic
      recycling has been used successfully in hospital settings. However, its
      usefulness in community settings, where the main burden of enteric fever resides,
      is challenging to manage due to logistics and a lack of infrastructure. Nalidixic
      acid resistance used to be a marker for clinical response to flouroquinolones;
      however, recent studies highlight the importance of decreased ciprofloxacin
      susceptibility as a better marker. Enteric fever, as a public health problem, has
      been tackled by protection of food and water supplies in the industrialised
      countries of the world. Nonetheless, that goal seems too far-fetched in the
      developing world where there are hundreds of villages, towns and cities without
      adequate infrastructures. Perhaps the key to solving this problem is combining
      point-of-use-purification of water (by chlorination) with the treatment of
      illness in the community. Treatment of chronic carriers is also necessary in
      order to halt the cycles of transmission.

PMID- 19745519
TI  - Typhi genes expressed during infection or involved in pathogenesis.
AB  - Salmonella enterica serovar Typhi (Typhi), the aetiologic agent of typhoid fever,
      is a human restricted pathogen. Elucidation of the interactions between the
      infected host and this pathogen is critical to understand infectious diseases but
      is deterred by a lack of in vivo infection assays, since Typhi uniquely infects
      humans and there is no suitable animal model. Macrophages can be used as an
      alternative model, as the ability to survive and replicate within these cells is
      thought to be one of the major pathogenesis determinants for Salmonella. Typhi
      genes that are expressed within human macrophages have been identified, as well
      as Typhi immunogenic proteins expressed in humans with typhoid. Known virulence
      factors of Salmonella are expressed during infection of macrophages, such as SPI
      2 encoded genes, supporting the validity of the model; however, many genes of
      unknown functions are also expressed. The importance of these genes should be
      investigated during future studies aimed at elucidating the intracellular
      lifestyle of this human-specific pathogen. This review describes Typhi genes
      expressed during infection or involved in cell interaction.

PMID- 19745520
TI  - Invasive salmonellosis in Malawi.
AB  - The incidence of invasive salmonellosis has increased among children and HIV
      infected adults in Malawi. This has been associated with the emergence of drug
      resistance in the non-typhoidal Salmonella serovars Enteritidis and Typhimurium.
      In contrast, S. Typhi isolates have remained fully sensitive to commonly used
      antibiotics and the estimated incidence of typhoid fever, although still present,
      has fallen slightly among both adults and children. Infection with S. Typhi is
      not closely associated with underlying immunosuppression but it is possible that
      the non-typhoidal Salmonellae have adapted to the person-person human
      transmission niche in this frequently immunosuppressed population. The huge
      burden of invasive salmonellosis in Malawi, the high associated mortality, and
      the recent emergence of drug resistance emphasise the need for a better
      understanding of the epidemiology and the need for vaccine development.

PMID- 19745521
TI  - Typhoid fever in sub-Saharan Africa: challenges of diagnosis and management of
      infections.
AB  - Typhoid fever, caused by Salmonella enterica serovar Typhi (S. Typhi), is a
      disease transmitted by the faecal-oral route. It continues to be a public health
      problem in many developing countries in sub-Saharan Africa. School-age children,
      especially those from resource-poor settings with inadequate water and sanitation
      systems, are disproportionately affected. It is estimated that a total of 400,000
      cases occur annually in Africa, an incidence of 50 per 100,000 persons per year.
      Lack of effective diagnosis often leads to inappropriate treatment and management
      of these infections. Additionally, the emergence and spread of S. Typhi strains
      having multiple resistance to nearly all commonly available drugs in most
      developing countries has been a major challenge to health care systems, reducing
      the effective treatment options for the disease, increasing treatment costs and
      increasing the risk of complications and death. Although not much data from sub
      Saharan Africa has been published, it seems clear that typhoid is common in
      Nigeria, Mali, Ethiopia and Kenya. Given the importance of information on disease
      incidence for targeting control measures, including improved sanitation and water
      supply, vaccination and assessing impact, priority should be given to
      strengthening surveillance systems for typhoid fever.

PMID- 19745522
TI  - Typhoid fever in Ethiopia.
AB  - This review focuses on the reports of salmonellosis by investigators in different
      parts of Ethiopia, in particular focusing on the levels of typhoid fever. Many of
      the reports are published in local journals that are not available online. There
      have been seven studies which diagnosed typhoid fever by laboratory culture and
      there is no coordinated epidemiological surveillance. All conducted research and
      reports from different health institutions in Ethiopia indicate that typhoid
      fever was still a common problem up to the most recent study in 2000 and that the
      extensive use of first-line drugs has led to the development of multiple drug
      resistance. In the sites covered by this review, the total number of published
      cases of typhoid fever dropped over time reflecting the decline in research
      capacity in the country. Data on the proportion of patients infected by different
      serovars of Salmonella suggest that the non-Typhi serovars of Salmonella are
      increasing. The published evidence suggests that typhoid fever is a current
      public health problem in Ethiopia although population based surveys, based on
      good microbiological diagnosis, are urgently needed. Only then can the true
      burden of enteric fever be estimated and the benefit of public health control
      measures, such as health education, safe water provision, improved food hygienic
      practices and eventually vaccination, be properly assessed.

PMID- 19745523
TI  - Epidemiology of typhoid and paratyphoid fever in India.
AB  - Enteric fever (typhoid and paratyphoid fever) is a major human bacterial
      infection. Although the disease is not common in industrialised countries, it
      remains an important and persistent health problem in developing nations.
      Hospital-based studies and outbreak reports from India indicate that enteric
      fever is a major public health problem in this country, with Salmonella enterica
      serovar Typhi (S. Typhi) the most common aetiologic agent but with an apparently
      increasing number of cases due to S. Paratyphi A (SPA). Because risk factors such
      as poor sanitation, lack of a safe drinking water supply and low socio economic
      conditions in resource-poor countries are amplified by the evolution of multidrug
      resistant salmonellae with reduced susceptibility to fluoroquinolone, treatment
      failure cases have been reported in India, which is associated with increased
      mortality and morbidity. Vaccination, which requires strict planning and proper
      targeting of the vulnerable age groups, is considered to be an effective tool in
      controlling this disease in endemic areas, given there is development of a
      conjugate vaccine against both serovars (S. Typhi and S. Para A).

PMID- 19745524
TI  - Kathmandu, Nepal: still an enteric fever capital of the world.
AB  - Kathmandu, the capital city of Nepal, has been previously coined an enteric fever
      capital of the world. Several studies have poignantly emphasized the significant
      burden of enteric fever within the local population and in travellers visiting
      the area. The population of Kathmandu is increasing and available figures suggest
      that enteric fever caused by Salmonella serovars Typhi and Paratyphi A show no
      significant signs of decreasing. Furthermore, our recent research demonstrates
      that the ratio of disease caused by these two organisms is shifting towards S.
      Paratyphi A. Here, we outline some of the major features of enteric fever in
      Kathmandu, including diagnosis, seasonal variation, transmission, and some
      characteristics of the infecting organisms. Our findings highlight the
      requirement for better understanding of the disease within the city; in turn,
      this will aid development of a targeted control strategy.

PMID- 19745525
TI  - Typhoid Fever in Italy, 2000-2006.
AB  - BACKGROUND: Typhoid fever remains endemic in the Apulia region of southern Italy.
      Here we investigate why this occurs despite increasing levels of environmental
      public health measures. METHOD: We collected morbidity data for typhoid fever in
      the Puglia region of Italy in the years 2000 to 2006 from the national mandatory
      surveillance system for infectious disease. RESULTS: In the last six years the
      rate of notified cases reduced substantially from approximately 1.1 per 100,000
      in 2000 to 0.4 per 100,000 in 2006. Higher rates were observed in the Puglia
      region when compared to the national rates. DISCUSSION: A reduction in the number
      of cases and chronic carriers occurred alongside improvements in environmental
      and public health measures. In particular, in recent years, the improvement in
      the depuration of raw fish and the elimination of sewage discharge into the sea
      seem to have led to a sharp decline in the incidence of typhoid fever in southern
      Italy.

PMID- 19745526
TI  - Specimens and culture media for the laboratory diagnosis of typhoid fever.
AB  - BACKGROUND: Culture of S. Typhi is necessary for the definitive diagnosis of
      typhoid fever and provides isolates for antibiotic susceptibility testing and
      epidemiological studies. However, current methods are not fully optimised and
      sourcing culture media and bottles for culture media may be problematic.
      METHODOLOGY: In two hospital laboratories in Viet Nam, comparisons of media for
      blood and stool culture were conducted. The effect of the volume of blood or
      stool on culture positivity rate was examined and direct plating of the blood
      buffy coat was trialed. RESULTS: For 148 suspected typhoid fever cases, ox bile
      broth (58 positive) and brain-heart infusion broth containing saponin (63
      positive), performed equally well. For 69 confirmed adult typhoid fever cases,
      large-volume (15 ml) blood culture gave the same sensitivity as 1 ml of bone
      marrow culture. For 44 confirmed typhoid fever cases, the direct plating of the
      buffy coat was positive in 28 cases. For 263 positive stool cultures, selenite F
      and selenite mannitol performed equally well and culturing 2 g rather than 1g
      increased the isolation rate by 10.5%. CONCLUSIONS: For the diagnosis of typhoid
      fever by blood culture the medium should be a rich nutrient broth containing a
      lysing agent. In adults 1 ml bone marrow or 15 ml blood culture gave similar
      results. Where isolates are needed for susceptibility testing or epidemiological
      studies, but resources for culture are scarce, direct plating of the blood buffy
      coat can be used with a 50% fall in sensitivity compared to standard blood
      culture.

PMID- 19745527
TI  - Evaluation of false negativity of the Widal test among culture proven typhoid
      fever cases.
AB  - BACKGROUND: The Widal test is the most common, specific and quick diagnostic
      method available in the world for diagnosis of typhoid fever; however, false
      negativity is one of the obstructive features of the test. The aim of this study
      was to evaluate the associated factors with Widal test negativity in an endemic
      area. METHODS: Widal test negativity was retrospectively analyzed among culture
      proven typhoid fever cases. The potential features including age, gender,
      previous antibiotic usage, duration of symptoms, leucopoenia, hematocrit value,
      and erythrocyte sedimentation rate (ESR) were evaluated for association with
      Widal test negativity. RESULTS: A total of 166 culture-proven typhoid fever cases
      (93 or 56.0% males) were included in the study. The mean age +/- SD was 23.3 +/-
      10.6 years. Mean time of interval between first symptom and test performance time
      was 10.6 +/- 7.8 days. The Widal test (STO and/or STH) was found positive in 75
      cases (45.2%). The statistical analyses revealed that none of these variables
      were significant for false negativity of the Widal test. Age was found to be a
      possible factor for a false negative Widal test (p=0.06). CONCLUSION: Of existing
      compatible clinical findings, age should be considered in cases of Widal test
      negativity.

PMID- 19745528
TI  - Reflections on Dr. Montagnier's Nobel Prize for the discovery of HIV-1.

PMID- 19745529
TI  - Direct single-cell molecular analysis of plant tissues by video mass
      spectrometry.
AB  - Direct and quick molecular analysis of live plant single cells viewed under a
      video-microscope has been developed in their intact undamaged environment using
      nano-electrospray tip and mass spectrometers. This method has been successful in
      identifying specific molecules in plant live single-cell analysis by mass
      spectrometry, and opens the possibility to compare different cell types from
      different tissues with morphological evidence in undamaged plants.

PMID- 19745530
TI  - Rapid and simple determination of phthalates in plastic toys by a thermal
      desorption-GC/MS method.
AB  - A thermal desorption (TD)-GC/MS method was applied for the determination of
      phthalates in plastic children's toys. The method, which does not need any
      cumbersome sample pretreatment such as solvent extraction, filtration and
      derivatization, has been proved to be useful not only as a sensitive analytical
      method to evaluate phthalate concentration in the toys, but also as a rapid and
      practical screening method to check whether the concentration exceeds the
      regulatory limit.

PMID- 19745531
TI  - Applications of strong interactions between photons and molecules to analytical
      sciences.
AB  - Spectroscopic measurements and applications to analytical sciences utilizing
      strong interactions between photons and molecules will be described. In
      particular, this report demonstrates high-sensitivity analysis of chemical
      species in solution through laser multiphoton ionization, and selective detection
      and characterization of the molecules located at solid surfaces and phase
      boundaries by using the method of second harmonic generation. Furthermore, new
      spectroscopic methods and sensitivity improvements utilizing the resonance of
      incident light photons with surface plasmons emerging on the surfaces of gold
      nanoparticles and nanostructures are presented. In addition, applications of
      surface plasmon resonance to spatio-selective plating to microscopic sites and to
      the field of nanobiotechnology are described, with special focusing on
      controlling biomolecules.

PMID- 19745532
TI  - Laser response of a quartz crystal microbalance: frequency changes induced by
      light irradiation in the air phase.
AB  - A weak laser irradiation (523-785 nm, 5-60 mW) onto an Au electrode surface of a
      27-MHz quartz crystal microbalance (QCM) caused a frequency increase (a mass
      decrease) in the air phase. These frequency changes depended on the wavelength of
      the irradiated laser in the order of 523 nm > 636 nm > 785 nm, which corresponds
      to the light absorbance of the Au electrode of the QCM. The laser response
      increased linearly with increasing laser power (5-60 mW). In addition, the laser
      response showed a maximum at the incidence angle of 72 degrees when the P
      polarized 636 nm laser was irradiated on the Au surface, due to the evanescent
      effect. These laser responses were also observed in the humid air of H2O, D2O,
      and in the vapors of various alcohols. Based on these findings, the observed
      frequency increase (mass decrease) can be explained by the photo-induced
      reversible desorption of water molecules from the Au electrode surface of the QCM
      due to the interfacial property changes.

PMID- 19745533
TI  - Application of poly[oxyethylene(dimethylimino)propyl-(dimethylimino)ethylene] as
      enzyme stabilizer for bilirubin oxidase immobilized electrode.
AB  - It has been shown that polyammonium cations comprising quaternary ammonium and
      hydrophilic groups such as amide and hydroxyl groups stabilize a redox enzyme
      bilirubin oxidase (BOD). The BOD catalyzes the reaction: 4[Fe(CN)6]4- + 4H+ + O2 
      -> 4[Fe(CN)6]3- + 2H2O, and has been a promising enzyme for use as a cathode
      catalyst in biofuel cells. In this study, the stabilizing effect of
      poly[oxyethylene(dimethylimino)propyl(dimethylimino)ethylene] (PA1) on BOD has
      been investigated. The sample solution containing BOD and the PA1 salt was kept
      at a given temperature, and the loss of the enzymatic activity was detected after
      given stored times. The activity decreased exponentially with stored time so that
      the first-order rate-constant of inactivation was determined. The inactivation
      rate-constant lowered with increasing the concentration of the PA1 salt,
      suggesting that BOD was stabilized by the association with the PA1 cation. The
      PA1 cation may act like a protective colloid or decrease the local disorder of
      BOD by its wrapping. A membrane-covered electrode containing BOD, PA1, and
      [Fe(CN)6](4-/3-) in the internal solution phase was examined in air-saturated
      aqueous solution. The electrode gave a well-defined current-potential curve with
      a steady state limiting current due to the PA1-[Fe(CN)6](4-/3-) polyion complex
      mediated bioelectrocatalytic current for the reduction of O2. The decreasing of
      the steady state limiting current became slower in the presence of the PA1 salt,
      indicating again the stabilizing effect of PA1 cation on BOD.

PMID- 19745534
TI  - A tyrosinase biosensor based on ZnO nanorod clusters/nanocrystalline diamond
      electrodes for biosensing of phenolic compounds.
AB  - An amperometric biosensor was constructed by using ZnO nanorod clusters as
      platforms for immobilizing tyrosinase on the nanocrystalline diamond (NCD)
      electrodes. The results showed that ZnO nanorod clusters provided an advantageous
      microenvironment due to their favorable isoelectric point (IEP) for tyrosinase
      loading; immobilized tyrosinase generally retained its activity. The
      tyrosinase/ZnO/NCD electrode showed a linear response range of 1-210 and
      sensitivity of 179.9 microA mmol(-1) cm(-2) for p-cresol. The corresponding
      values were 1-190 and 90.2 for phenol, and 1-250 and 121.3 for 4-chlorophenol.
      The low detection limits were estimated to be 0.2 microM for p-cresol, 0.5 microM
      for phenol, and 0.4 microM for 4-chlorophenol (S/N = 3). The prepared enzyme
      electrode could keep 85% of its original activity after intermittent use for 4
      weeks when stored in a dry state at 277 K. Therefore, the ZnO nanorod cluster
      thin films have potential applications as platforms to immobilize other enzymes
      and bioactive molecules in biosensors.

PMID- 19745535
TI  - An electrochemical sensor for phenylephrine based on molecular imprinting.
AB  - Molecularly imprinted polymers (MIPs) were applied as molecular recognition
      elements to an electrochemical sensor for phenylephrine. A MIPs membrane was
      created on a glassy carbon electrode. SEM revealed a gradual change on the
      morphology of modified electrodes as the ratios of function monomer and cross
      linking varied. When the ratio was 4:40, the surface morphology between the
      imprinted electrode (M-electrode) and the control electrode (N-electrode) became
      unambiguously different. This artificial receptor exhibited high selectivity for
      the template compared to closely related analogue. The response of the sensor
      varied in different concentration range might due to the heterogeneity of the
      MIPs membrane. This sensor was also used to determine phenylephrine in tablet
      samples.

PMID- 19745536
TI  - Noncompetitive immunodetection of benzaldehyde by open sandwich ELISA.
AB  - Benzaldehyde (Bz) is a typical fragrant compound for peach-flavored beverages. In
      the food and beverage industries there is great demand for a sensitive and easy
      detection system of Bz in order to ensure product quality control and to avoid
      contamination. For the noncompetitive detection of Bz, we applied an open
      sandwich enzyme-linked immunosorbent assay (OS-ELISA) utilizing an antigen
      dependent reassociation of antibody variable region fragments, VH and VL. We
      cloned the VH and VL genes of an anti-Bz monoclonal antibody, and the fragments
      were individually expressed and purified as a bacterial alkaline phosphatase
      (BAP)-conjugated form for VH and as a thioredoxine (Trx)-fused form for VL,
      respectively. Using these VH and VL fragments, we successfully constructed the OS
      ELISA system for Bz detection. The Bz-induced formation of a trimolecular complex
      composed of VH-BAP/Bz/Trx-VL was readily detected by a dose-dependent increase in
      the BAP activity of the VH-fusion protein.

PMID- 19745537
TI  - Verification of a specific reaction between an airborne antigen and an
      immobilized antibody at a gas-solid interface.
AB  - With a specific and strong molecular-recognition capability cultivated in humoral
      acquired immunity, an antibody has been extensively utilized in various
      applications, such as diagnostics and therapy. However, so far most of its uses
      have been limited to be in the liquid phase. In view of its potential uses, such
      as a gas-phase biosensor or a high-performance air filter, we have tried to
      verify a previously undescribed binding reaction between protein antigens and
      corresponding antibodies immobilized on a solid surface by using fluorescence
      resonance energy transfer between the two. Our data showed that the antibody on a
      solid surface specifically reacted with a protein antigen supplied from the gas
      phase under the normal ambient condition. Also discovered was that the reaction
      occurred even faster than that in the liquid phase under several assay
      conditions.

PMID- 19745538
TI  - Methacrylate-ester-based reversed phase monolithic columns for high speed
      separation prepared by low temperature UV photo-polymerization.
AB  - Butyl methacrylate-based reversed phase capillary monolithic columns were
      prepared using ultraviolet (UV) photo-polymerization. The effects of two photo
      polymerization conditions (UV irradiation intensity and polymerization
      temperature) on the column characteristics were investigated. Both the higher UV
      irradiation intensity and the lower polymerization temperature lead to the
      superior column efficiency. The column prepared under the optimized conditions
      was evaluated through the separation of the uracil and five alkylbenzenes in the
      linear flow rate range of 1-110 mm/s. At 1 mm/s, all analytes were well separated
      (N = 36000-45000 plates/m). The high speed separation within 8 s was performed at
      110 mm/s (back pressure, 33 MPa) at room temperature, whereas the peaks eluted
      earlier were overlapped partially. The relationship between the flow rate and the
      back pressure indicated that some kind of structural change of the monolith might
      occur in 50-110 mm/s, although no visible or hysteresis changes of the monolith
      were observed after the measurement.

PMID- 19745539
TI  - Determination of amphetamines in hair by GC/MS after small-volume liquid
      extraction and microwave derivatization.
AB  - We report here on the results of a procedure for the determination of amphetamine
      drugs in hair. The procedure is simple and sensitive. The results from the
      procedure using small-volume extraction matches perfectly with those either from
      using the derivatization method or selected ion monitoring (SIM) detection. We
      validated our method using four different amine drugs, including amphetamine,
      methamphetamine, methylenedioxy-amphetamine and methylenedioxy-methamphetamine.
      The detection limit for these drugs is about 50 +/- 7.5 pg/mg in hair and the
      intra-day and inter-day reproducibility are within 15% at most drug
      concentrations. Moreover, we also showed the utility of the procedure in analyses
      of authentic hair samples taken from amphetamine abusers, and demonstrated that
      the method meets the requirement for the analysis of a trace amounts of
      amphetamines in human hair.

PMID- 19745540
TI  - Quick and sensitive determination of flavonoids by capillary electrophoresis
      potential gradient detection.
AB  - A capillary electrophoresis (CE)-potential gradient detection (PGD) method was
      developed for quick and sensitive determinations of puerarin, farrerol and
      baicalin. The flavonoids were baseline separated in 1.9 min with a buffer
      comprised of 20 mM tris(hydroxymethyl)aminomethane (Tris) and 3 mM HCl at pH
      8.69. The analysis time is, to the best of our knowledge, the shortest for the CE
      analysis of flavonoids. The association constants, determined by affinity CE,
      suggested an ion-dipole or ion-induced dipole interaction between Tris and
      flavonoid molecules. The detection limits, in the range of 0.068 and 0.116 mg L(
      1), were lower than the early reported UV and chemiluminescence detection
      techniques. A solvent-extraction method was coupled to CE to determine baicalin
      in a Chinese herbal preparation Scutellaria Baicalensis Georgi. The concentration
      of baicalin in the sample was determined to be 5.1%. Validation of the method
      suggested its applicability in real sample analysis.

PMID- 19745541
TI  - Simultaneous determination of trace polycyclic and nitro musks in water samples
      using optimized solid-phase extraction by gas chromatography and mass
      spectrometry.
AB  - This study intended to develop a robust and sensitive method for simultaneous
      determination of polycyclic musks (HHCB and AHTN) and nitro musks (musk xylene
      (MX) and musk ketone (MK)) in water samples using optimized solid-phase
      extraction (SPE) by gas chromatography and mass spectrometry (GC-MS). The SPE
      procedure was optimized in terms of selections of SPE cartridge, sample pH,
      elution process, etc. The method detection limits (MDLs) were from 0.09 to 0.18
      ng L(-1) for the analytes. The recoveries ranged from 88.3 to 104.1% in spiked
      deionized water and from 86.4 to 106.8% in groundwater samples, respectively. The
      proposed approach was also validated by detecting real samples. The results
      revealed that HHCB and AHTN were ubiquitous in the local aquatic matrices.
      Furthermore, nitro musks were found in some aquatic matrices, which is consistent
      with the fact that nitro musks are still being produced and applied in China.

PMID- 19745542
TI  - Blank membranes versus ionophore-based membranes for the selective determination
      of H+.
AB  - A pH electrode for the selective determination of H+ was introduced. Both
      phosphorated calix[6]arene and a N,N'-bisethoxycarbonyl-1,10-diaza-4,7,13,16
      tetraoxacyclo-octadecane (DZCE) were used as new H+-ionophores. The calibration
      graphs of the obtained electrodes exhibits satisfactory Nernstian slopes. The
      electrodes were compared to blank membranes (without any ionophoric substances)
      for the first time. Selectivity coefficients of the studied electrodes towards
      several inorganic cations were calculated. The relative selectivity coefficient
      (RSC) was applied for evaluating the selectivity properties of H+-electrode using
      a mathematical equation. The electrodes were applied for the determination of
      different inorganic and organic acids.

PMID- 19745543
TI  - Prediction of gas-to-olive oil partition coefficients of organic compounds using
      an artificial neural network.
AB  - The main aim of the present work was development of a quantitative structure
      property relationship method using an artificial neural network (ANN) for
      predicting gas-to-olive oil partition coefficients of organic compounds. As a
      first step, a multiple linear regression (MLR) model was developed; the
      descriptors appearing in this model were considered as inputs for the ANN. These
      descriptors are: solvation connectivity index chi(-1), hydrophilic factor,
      conventional bond-order ID number, dipole moment and a total size index/weighted
      by atomic masses. Then a 5-5-1 neural network was generated for the prediction of
      gas-to-olive oil partition coefficients of 179 organic compounds including
      hydrocarbons, alkyl halides, alcohols, ethers, esters, ketones and benzene
      derivatives. The values of standard error for training, test and validation sets
      are 0.127, 0.122 and 0.162, respectively for ANN model. Comparisons between these
      values and other obtained statistical values reveal the superiority of the ANN
      model over the MLR one.

PMID- 19745544
TI  - Construction of an efficacious model for a nondestructive identification of
      traditional Chinese medicines Liuwei Dihuang pills from different manufacturers
      using near-infrared spectroscopy and moving window partial least-squares
      discriminant analysis.
AB  - This paper reports on the construction of an efficacious model for a non-invasive
      identification of traditional Chinese medicines, Liuwei Dihuang pills from
      different manufacturers, on the basis of near-infrared spectra (NIRS) coupled
      with moving window partial least-squares discriminant analysis (MWPLSDA).
      Considering the continuity of near-infrared spectral measurements, MWPLSDA is
      used to identify continuous and highly classification-related information
      intervals, a simple, yet effective classification model that can be developed for
      identifying accurate 150 Liuwei Dihuang pills from five different manufacturers.
      Meanwhile, the method is compared with some traditional pattern-recognition
      methods including principal component analysis (PCA), linear discriminant
      analysis (LDA) and partial least-squares discriminant analysis (PLSDA). The
      obtained results show that the method not only can reduce the operation time, but
      also significantly improves the classification accuracy. Hence, the
      nondestructive method can be expected to be promising for more practical
      applications on quality control and the discrimination of traditional Chinese
      medicine.

PMID- 19745545
TI  - Practical method for the detection of tetracyclines in honey by HPLC and
      derivative UV-Vis spectra.
AB  - A technique to detect residual tetracyclines (TCs) in honey by HPLC and
      derivative UV-Vis spectra is examined in this study. Chromatograms of honey
      products often experience overlapped peaks and sloping background due to similar
      retention properties of components or to the presence of impurities. The
      derivatives provide resolution of overlapped peaks in an UV-Vis spectrum and
      eventually bring chromatograms that show pure elution behavior of TCs.
      Calibration models for oxytetracycline (OTC), tetracycline (TC) and
      chlortetracycline (CTC) are built out of the derivative spectra of standard
      solutions of honey and their prediction abilities are examined. The results show
      that the calibration models for OTC, TC and CTC can yield sufficient levels for
      the determination. The technique reported here may be effectively used for
      quantitative determination of TCs.

PMID- 19745546
TI  - Measurement of the transport activities of bile salt export pump using LC-MS.
AB  - The high performance liquid chromatography-electrospray ionization-mass
      spectrometry method has been applied to the measurement of bile acid transport
      activities in membrane vesicles obtained from a human bile salt export pump
      expressing Sf9 cells. The amounts of bile acids transported using the human bile
      salt export pump expressing Sf9 cells were determined using liquid chromatography
      electrospray ionization-mass spectrometry method and the values of the kinetic
      parameters were determined to be comparable with those obtained using
      radioisotope-labeled substrates. The developed method was highly useful for the
      measurements of bile acid transport activities.

PMID- 19745547
TI  - Immobilization of glucose oxidase on a poly(dimethylsiloxane) layer by using
      poly(L-lysine) as a polymer backbone.
AB  - Poly(dimethylsiloxane) (PDMS)-coated platinum electrodes modified with glucose
      oxidase (GOx) have been prepared from poly(L-lysine) (polymer backbone),
      glutaraldehyde (cross-linking agent) and poly(ethylene glycol) units. To
      fabricate a GOx layer by applying cross-linking chemistries, the PDMS layer was
      treated with oxygen plasma to replace silane groups with silanol groups.
      Optimization for the chemical fabrication of a GOx layer resulted in a simple
      preparation of sensors with a wide detectable range (0.1-6.0 mM) and without
      interference from hydrogen peroxide produced by a GOx reaction and the other in
      biological samples.

PMID- 19745548
TI  - Application of 4-iodophenol-enhanced luminol chemiluminescence to direct
      detection of horseradish peroxidase encapsulated in liposomes.
AB  - 4-Iodophenol was applied to an enhancer in the direct detection of horseradish
      peroxidase (HRP) encapsulated in liposomes by using luminol chemiluminescence
      (CL). Luminol, 4-iodophenol and hydrogen peroxide permeate into the inner phase
      of liposomes containing HRP, resulting in the progress of 4-iodophenol-enhanced
      luminol CL catalyzed by HRP in liposomes. The CL intensity observed in liposomes
      was a factor of 150 greater than that observed in a lipid-free bulk solution. The
      detection limit in the direct detection of HRP encapsulated in liposomes was
      sensitive by a factor of 30 compared with that in a lipid-free bulk solution. 4
      Iodophenol effectively functioned as an enhancer in HRP-catalyzed luminol CL in
      liposomes.

PMID- 19745549
TI  - Extraction studies of uranium(VI), plutonium(IV) and americium(III) from nitric
      acid using the bi-functional carbamoyl methyl sulfoxide ligands.
AB  - The extraction behavior of new bi-functional ligands containing sulfoxide and
      amide groups viz. N,N'-dibutyl carbamoyl methyl phenyl sulfoxide (L1) and N,N'
      dibutyl carbamoyl methyl benzyl sulfoxide (L2) towards the U(VI), Pu(IV) and
      Am(III) ions from nitric acid was studied. Both of these extractants showed
      appreciable extractions for U(VI) and Pu(IV) from 1 to 9.5 M nitric acid
      concentrations. Am(III) did not show an appreciable extraction under the
      conditions studied. The species extracted from a nitric acid medium correspond to
      the compositions of [UO2(NO3)(2).2L] and [Pu(NO3)4.2L] for L1 and a mixture of
      [UO2(NO3)(2).2L], [UO2(NO3)2.L] and [Pu(NO3)(4).2L] for the L2. The conditional
      extraction constant (Kex) values for the Pu(IV) with L1 and L2 were estimated for
      the first time, and found to be 6.21 x 10(2) and 5.64 x 10(2) mol(-4) dm,
      respectively.

PMID- 19745551
TI  - Vascular dilation responses of rat small mesenteric arteries at high
      intravascular pressure in spontaneously hypertensive rats.
AB  - BACKGROUND: Hypertension is associated with remodeling and mechanical alterations
      of resistance arteries. Numerous studies have investigated the mechanical and
      morphometric properties of small arteries obtained from hypertensive animals and
      humans. However, the functional properties of resistance arteries from
      normotensive and hypertensive subjects have only been examined under normotensive
      conditions. The objective of the present study was to evaluate the dilation
      responses of small mesenteric arteries (SMA) from spontaneously hypertensive rats
      (SHR) at various levels of intraluminal pressure. METHODS AND RESULTS: SMA
      segments from Wistar Kyoto (WKY) rats and SHR were pressurized using pressure
      myography. Endothelium-dependent and -independent dilation responses of the SMA
      were examined under 3 different intravascular pressures (50, 80 and 120 mmHg).
      Endothelium-dependent dilation was evaluated by measuring vasodilator responses
      to increasing doses of acetylcholine or increases in intraluminal flow rate.
      Endothelium-independent vasodilator function was examined by using sodium
      nitroprusside. The results indicate that both endothelium-dependent and 
      independent dilation responses of SMA from WKY progressively decrease with
      increased intravascular pressure. In contrast, all dilatation responses of the
      SMA from SHR were enhanced at higher intraluminal pressures. CONCLUSIONS: These
      findings of differential sensitivity to luminal pressure should be considered
      during in vitro examination of vessels from normotensive and hypertensive
      subjects.

PMID- 19745552
TI  - Pro12Ala polymorphism of the peroxisome proliferatoractivated receptor-gamma gene
      is associated with metabolic syndrome and surrogate measures of insulin
      resistance in healthy men: interaction with smoking status.
AB  - BACKGROUND: The Pro12Ala polymorphism (rs1801282), a nonsynonymous substitution
      of peroxisome proliferator-activated receptor-gamma (PPARG), has been robustly
      associated with type 2 diabetes. However, its role in metabolic syndrome (MetS)
      remains poorly understood. The associations among rs1801282, MetS and surrogate
      measures of insulin resistance (IR) were investigated in the present study.
      METHODS AND RESULTS: A cross-sectional population-based survey of 572 unrelated
      healthy male Argentinian blood donors with normal findings on medical examination
      and not taking any medication was conducted. MetS was assessed using the National
      Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATP III) criteria,
      and the HOMA-IR, and QUICKI were calculated. Genotyping of rs1801282 was
      performed using RFLP-PCR. The prevalence of MetS was 26.2%. The Pro/Ala genotype
      (and the Ala12 allele) was associated with a high risk for MetS (odds ratio (OR)
      1.67 [95% confidence interval (CI) 1.03-2.72], P=0.0394). This was highlighted
      among nonsmokers (OR 2.20 [95%CI 1.25-3.88], P=0.0059). ANCOVA confirmed an
      interaction between smoking status and this association (P=0.031). Ala12 carriers
      had a higher waist circumference than noncarriers (P=0.0065). Among nonsmokers,
      surrogates of IR, such as HOMA-IR, were significantly higher in Ala12 carriers
      than in noncarriers (P<0.05). CONCLUSIONS: Healthy men, in particular nonsmokers,
      carrying the Ala12 allele of PPARG rs1801282 polymorphism, have a high risk for
      MetS and IR.

PMID- 19745553
TI  - Solutions for retention of female cardiologists: from the survey of gender
      differences in the work and life of cardiologists.
AB  - BACKGROUND: To prevent a future shortage of cardiologists, it is important for
      female cardiologists to continue working. Gender differences in the professional
      and private lives of cardiologists, as well as the barriers to work for female
      cardiologists, were surveyed. METHODS AND RESULTS: In August 2007, a
      questionnaire was mailed to all 195 faculty members/fellows and 155 alumni of the
      Department of Cardiovascular Medicine at Nippon Medical School. More female
      cardiologists were dissatisfied with their job than male cardiologists (34% vs
      17%, P<0.005). Women reported greater career limitation by family
      responsibilities and housework. Men and women both reported that long working
      hours was the most problematic issue, but significantly more women reported this
      than men (76% vs 94%, P<0.05). Female cardiologists were more concerned about
      occupational radiation exposure (88% vs 59%, P<0.01) and wanted opportunities for
      retraining after childcare leave (100% vs 76%, P<0.01). CONCLUSIONS: The
      following measures should be taken: (1)establishment of more family-friendly
      working conditions in hospitals, (2)provision of various work positions that
      allow more flexibility and predictability for women, (3)establishment of a
      retraining system, and (4)development of work and research opportunities that are
      attractive to women. The Japanese Circulation Society is expected to establish a
      retraining system at certified institutions.

PMID- 19745554
TI  - Papillary muscle suspension concomitant with approximation for functional mitral
      regurgitation.
AB  - BACKGROUND: Papillary muscle (PM) suspension concomitant with mitral annuloplasty
      and PM approximation (PMA) has been developed for functional mitral regurgitation
      (MR). In the present study, the early effect of PM suspension (PMS) on the
      postoperative mitral geometry and diastolic mitral tethering was investigated.
      METHODS AND RESULTS: Subjects were 22 patients with left ventricular dysfunction
      and functional MR who underwent mitral annuloplasty and PMA with or without
      suspension from 2004 to 2008. The purpose of PMS is to maintain the mitral
      complex geometry and prevent future mitral tethering caused by left ventricular
      remodeling. The mean age was 64 +/-10 (range 39-85) years. The submitral
      apparatus geometry was measured by echocardiography. PM and mitral inflow angles
      in the anterior-directional suspension group were significantly larger than those
      in the posterior-directional suspension group (57 +/-7 degrees vs 46 +/-9 degrees
      , P=0.017 and 78 +/-9 degrees vs 60 +/-6 degrees , P<0.001, respectively), which
      were comparable to the normal control. In the posterior-directional suspension
      group, the transmitral pressure gradient was higher and restrictive mitral
      filling pattern remained postoperatively in 2 cases of the group. CONCLUSIONS:
      Anterior-directional suspension is preferable to the posterior one in terms of
      diastolic mitral filling.

PMID- 19745555
TI  - Albumins with new functions and clinical applications.

PMID- 19745556
TI  - Structural and mutagenic approach to create human serum albumin-based oxygen
      carrier and photosensitizer.
AB  - SUMMARY: Human serum albumin (HSA) is a versatile protein found at high
      concentration in blood plasma and binds a range of insoluble endogenous and
      exogenous compounds. We have shown that complexation of functional molecules into
      HSA creates unique proteins never seen in nature. Complexing an iron
      protoporphyrin IX into a genetically engineered heme pocket of recombinant HSA
      (rHSA) generates an artificial hemoprotein, which binds O(2) reversibly in much
      the same way as hemoglobin. A pair of site-specific mutations, (i) introduction
      of a proximal histidine at the Ile-142 position and (ii) substitution of Tyr-161
      with Phe or Leu, allows the heme to bind O(2). Additional modification on the
      distal side of the heme pocket provides rHSA(triple mutant)-heme complexes with a
      variety of O(2) binding affinity. Complexing a carboxy-C(60)-fullerene (CF) into
      HSA generates a protein photosensitizer for photodynamic cancer therapy. Energy
      transfer occurs from a photoexcited triplet-state of HSA-CF (HSA-(3)CF(*)) to
      O(2), forming singlet oxygen ((1)O(2)). This protein does not show dark
      cytotoxicity, but induceds cell death under visible light irradiation.

PMID- 19745557
TI  - Albumin as fatty acid transporter.
AB  - SUMMARY: Fatty acids play critical roles in mammalian energy metabolism.
      Moreover, they are important substrates for the synthesis of membrane
      phospholipids and biologically active compounds like eicosanoids and
      leukotrienes. Because of their low solubility in aqueous solutions such as blood
      plasma and interstitial fluid, fatty acids are in need of binding proteins to
      increase their concentration in vascular and interstitial compartments. Albumin
      acts as main fatty acid binding protein in extracellular fluids. Plasma albumin
      possesses about 7 binding sites for fatty acids with moderate to high affinity,
      enhancing the concentration of fatty acids by a several orders of magnitude.
      Despite the high affinity of albumin for fatty acids, uptake of fatty acids by
      parenchymal cells such as skeletal and cardiac myocytes seems not to be hampered
      by albumin. In contrast, experimental findings suggest that albumin may
      facilitate the uptake of fatty acids by organs in need of these substrates. In
      the present overview the following issues will be briefly discussed: (i)
      transport and storage of fatty acids in the mammalian body, (ii) biosynthesis of
      albumin in the liver, (iii) localization and concentration of albumin in body
      fluids, (iv) interactions between albumin and fatty acids, (v) albumin structure
      and fatty acid binding sites, (vi) uptake of fatty acids by organs and roles for
      plasma albumin and (vii) lessons from patients and experimental animals lacking
      plasma albumin.

PMID- 19745558
TI  - Albumin as a nitric oxide-traffic protein: characterization, biochemistry and
      possible future therapeutic applications.
AB  - SUMMARY: Nitric oxide (NO) is a ubiquitous molecule involved in multiple cellular
      functions. Inappropriate production of NO may lead to disease states. To date,
      pharmacologically active compounds that release NO within the body, such as
      organic nitrates, have been used as therapeutic agents, but their efficacy is
      significantly limited by rapid NO release, toxicity and induction of tolerance.
      Therefore, novel NO donors with better pharmacological and phamacokinetic
      properties are highly desirable. The S-nitrosothiol fraction in plasma is largely
      composed of S-nitrosylated human serum albumin (SNO-HSA) and that is why we are
      testing whether this albumin form can be used as a NO traffic protein. We have
      found that oleate and other endogenous ligands increase SNO-HSA formation in
      vitro. The cytoprotective effect of SNO-HSA in a ischemia/reperfusion model and
      its antiapoptotic effect on HepG2 cells treated with anti-Fas antibody were
      pronounced and could be enhanced by binding of oleate. The enhancement of S
      transnitrosation to the HepG2 cells could be completely blocked by filipin III, a
      caveolae inhibitor. These findings indicate that a clinical application of SNO
      HSA is expected as potent NO supplementary therapy and that fatty acids may serve
      as novel types of mediators for S-transnitrosation.

PMID- 19745559
TI  - The versatile MHC class I-related FcRn protects IgG and albumin from degradation:
      implications for development of new diagnostics and therapeutics.
AB  - SUMMARY: The half-life of the two most abundant proteins in blood, immunoglobulin
      G (IgG) and serum albumin, is extraordinary (approximately 19-23 days) compared
      to other circulating proteins. This phenomenon secures a broad biodistribution
      throughout the body of both molecules. The long half-life has made IgG the
      natural choice for engineering of antibody based therapeutics, while albumin is
      used as a fusion partner for or carrier of drugs. Remarkably, the half-life of
      these unrelated proteins has been shown prolonged by a receptor recycling pathway
      mediated by a common cell bound receptor named the neonatal Fc receptor (FcRn).
      This review summarizes our current understanding of FcRn function and discusses
      its relevance for development of new IgG and albumin based therapeutics and
      diagnostics.

PMID- 19745560
TI  - Ischemia modified albumin: a novel biomarker for the detection of cardiac
      ischemia.
AB  - SUMMARY: The diagnosis of cardiac ischemia remains a challenge in contemporary
      emergency medicine. A blood-borne biomarker is an attractive alternative to
      cardiac imaging or stress testing as it would be cheaper and logistically faster
      to obtain. A number of candidate biomarkers have been proposed for the detection
      of cardiac ischemia; however, only Ischemia Modified Albumin (IMA) has been
      released for clinical use. IMA is a good discriminator between ischemic and non
      ischemic patients. Changes in IMA concentration have shown to occur during
      coronary angioplasty-induced ischemia. Clinical studies indicate that IMA appears
      to offer on admission an early test which can be combined with
      electrocardiographic findings and cardiac troponin measurements for the early
      exclusion of acute coronary syndrome. IMA is an independent predictor of short
      and long term adverse outcomes in patients with acute chest pain. However, this
      test is relatively new and uncertainties remain. Elevations of IMA occur in
      conditions other than chest pain, thus questioning its specificity. The mechanism
      of IMA formation and the precise entity being measured are not fully known.
      Nevertheless, IMA measurement remains the only current clinical biomarker which
      may be used for the diagnosis of patients suspected of cardiac ischemia.

PMID- 19745561
TI  - Lessons from the crystallographic analysis of small molecule binding to human
      serum albumin.
AB  - SUMMARY: Human serum albumin (HSA) is an abundant and highly soluble plasma
      protein with the capacity to bind a remarkably diverse set of lipophilic anionic
      compounds so that it fulfils important roles in the transport of nutrients,
      hormones and toxins. The protein attracts great interest from the pharmaceutical
      industry since it can also bind a variety of drug molecules, impacting their
      delivery and efficacy. Our understanding of the binding and transport properties
      of albumin has been transformed by structural studies of the protein, in which
      crystallographic analysis has played a leading role. This review summarises the
      main insights to have accrued from this work, highlighting the significant
      advances that have been made but also pointing out some of the challenges ahead.
      Since further progress is likely to benefit from increased structural scrutiny of
      HSA, methodological developments instrumental to the success of crystallographic
      analysis of the protein are discussed in some detail.

PMID- 19745562
TI  - Updates on contemporary protein binding techniques.
AB  - SUMMARY: Automated high-throughput techniques have become key to improving
      existing as well as new techniques associated with protein binding analysis. A
      wide variety of methods and experimental conditions are used for estimating
      protein binding as well as binding affinity, such as ultrafiltration and affinity
      chromatography. These methods rely either on the separation of a bound and free
      drug for subsequent conventional analysis or change in intrinsic parameters such
      as conformational properties of the protein. More recently developed techniques
      include surface plasmon resonance and solid-phase microextraction. Photoaffinity
      labeling, site-directed mutagenesis and x-ray crystallography are valuable
      techniques to identify the locations of binding sites on a protein. A new high
      throughput assay based on the distribution of a drug among plasma water, plasma
      proteins, and solid-supported lipid membranes (Transil) has been reported to
      produce valid results, even for drugs that are strongly bound to plasma proteins.
      This new method may be suited for examining highly lipophilic drugs that adsorb
      onto surfaces due to their low solubility in aqueous media. Such a method may
      promote drug discovery and development for high-throughput determination of
      protein binding.

PMID- 19745563
TI  - VKORC1 diplotype-derived dosing model to explain variability in warfarin dose
      requirements in Asian patients.
AB  - SUMMARY: Warfarin-induced bleeding complications and high inter-patient
      variability are major hindrances to oral anticoagulant therapy. The present study
      identifies the influence of VKORC1 diplotypes, CYP2C9 and CYP2C19 variants on
      warfarin disposition and dose requirements in Chinese patients (n=107). The study
      subjects were genotyped for VKORC1, CYP2C9 and CYP2C19 polymorphic variants.
      Weekly warfarin dose requirements and S-warfarin clearance were stratified by
      VKORC1, CYP2C9 and CYP2C19 pharmacogenetics. The major VKORC1 diplotypes were H1
      H1 (62%), H1-H7 (18%) and H1-H(*)(b) (10%). Warfarin dose requirements were
      significantly lower in patients with VKORC1 H1-H1 and H1-H(*)(a) diplotypes
      compared to patients harboring the H1-H7 and H1-H(*)(b) diplotypes (P<0.05).
      Hepatic tissues with H1-H1 diplotype had significantly lower expression of VKORC1
      mRNA compared with liver tissues carrying the H1-H7 and H1-H(*)(b) diplotypes
      (P=0.006). The percent variability explained by VKORC1 diplotype status was 59.1%
      while the CYP2C9 genotype status accounted for 6.9% variability in warfarin dose
      requirements. Patient age and weight were significant covariates accounting for
      29% and 8.6% of warfarin dose variability, respectively. The present study shows
      that VKORC1 diplotype status, CYP2C9 genotype, age and weight are significant
      covariates, accounting for 73.4% of interindividual variability in warfarin dose
      requirements among Chinese patients. Translation of these findings into clinical
      guidelines for warfarin dosing may be required to assess its impact on the safety
      and efficacy of warfarin.

PMID- 19745564
TI  - Comparative pharmacodynamics of olmesartan and azelnidipine in patients with
      hypertension: a population pharmacokinetic/pharmacodynamic analysis.
AB  - SUMMARY: The objectives of this study were to identify the factors influencing
      antihypertensive response to the angiotensin receptor blocker, olmesartan
      medoxomil, or the calcium channel blocker, azelnidipine, and to discuss the
      possibility of utilizing them as predictors for drug selection prior to therapy.
      A two-way crossover study of olmesartan medoxomil and azelnidipine was conducted
      in 29 patients with mild to moderate essential hypertension. The 24-hour
      ambulatory blood pressure measurements (ABPM) and plasma drug concentrations were
      obtained on the first and at the end of each treatment period, and were analyzed
      using population pharmacokinetic/pharmacodynamic (PK/PD) modeling approach. The
      population PK/PD models considering circadian variations in baseline blood
      pressure well described the observed plasma drug concentrations and 24-hour ABPM
      profiles. Pre-treatment plasma renin activity (PRA) was identified as a
      significant covariate on the maximum drug effect (E(max)) of olmesartan, whereas
      azelnidpine E(max) was independent of patient background characteristics
      investigated. No patient was found to have a high E(max) to one agent who also
      had a high E(max) to the other. In conclusion, the effects of olmesartan
      medoxomil and azelnidipine were modestly correlated with pharmacokinetic
      profiles, and the pre-treatment PRA level could be a useful determinant of
      responsiveness in selecting olmesartan medoxomil and azelnidipine.

PMID- 19745565
TI  - Microdose clinical trial: quantitative determination of nicardipine and
      prediction of metabolites in human plasma.
AB  - SUMMARY: A sample treatment procedure and high-sensitive liquid
      chromatography/tandem mass spectrometry (LC/MS/MS) method for quantitative
      determination of nicardipine in human plasma were developed for a microdose
      clinical trial with nicardipine, a non-radioisotope labeled drug. The calibration
      curve was linear in the range of 1-500 pg/mL using 1 mL of plasma. Analytical
      method validation for the clinical dose, for which the calibration curve was
      linear in the range of 0.2-100 ng/mL using 20 microL of plasma, was also
      conducted. Each method was successfully applied to making determinations in
      plasma using LC/MS/MS after administration of a microdose (100 microg) and
      clinical dose (20 mg) to each of six healthy volunteers. We tested new approaches
      in the search for metabolites in plasma after microdosing. In vitro metabolites
      of nicardipine were characterized using linear ion trap-fourier transform ion
      cyclotron resonance mass spectrometry (LIT-FTICRMS) and the nine metabolites
      predicted to be in plasma were analyzed using LC/MS/MS. There is a strong
      possibility that analysis of metabolites by LC/MS/MS may advance to utilization
      in microdose clinical trials with non-radioisotope labeled drugs.

PMID- 19745566
TI  - Cytochrome P450-dependent drug oxidation activity of liver microsomes from
      Microminipigs, a possible new animal model for humans in non-clinical studies.
AB  - SUMMARY: Small minipigs (Bland name, Micromini Pig; registered as a novel variety
      of pig in the Japanese Ministry of Agriculture, Forestry and Fisheries) were
      developed with the aim of non-clinical pharmacological/toxicological use. They
      were principally mated with<10 kg body weight at 7 months-old resulting in good
      handling. Cytochrome P450 (P450)-and flavin-containing monooxygenases (FMO)
      dependent drug oxidation activity of liver microsomes prepared from male
      Microminipigs (8 months-old) was compared with that for pooled dogs, monkeys, and
      humans. High P450 2D-dependent bufuralol 1'-hydroxylation and FMO-dependent
      benzydamine N-oxygenation activity was observed in liver microsomes from
      Microminipigs. Typical P450 1A, 2B, 2C, 2E, and 3A-dependent drug oxidation
      activity was also seen in Microminipigs. However, occasional differences might
      give undetected low P450 2A-dependent coumarin 7-hydroxylation in Microminipigs
      at 8-months-old, in contrast to liver microsomes from one 10-days-old
      Microminipis and commercially available pooled minipigs which had low but
      detectable coumarin 7-hydroxylation activity. The present results suggest that
      there is some overlap in Microminipig and human P450 substrate specificity. These
      findings should provide important information for greater understanding of drug
      metabolism in Microminipigs, as an experimental animal model for non-clinical
      use.

PMID- 19745567
TI  - Induction of extracytoplasmic function sigma factors in Bacillus subtilis cells
      with membranes of reduced phosphatidylglycerol content.
AB  - The Bacillus subtilis gene pgsA, which codes for the phosphatidylglycerophosphate
      synthase that catalyzes the committed step for the synthesis of
      phosphatidylglycerol (PG), is essential since Pspac-pgsA cells require IPTG for
      growth. Removal of the inducer caused a dramatic decrease of PG content in the
      membranes of cells and retarded growth. At 60 min and 120 min after removal, it
      was reduced to 14.1% and 8.9% of total lipid, respectively, from an initial
      content of 28.1%. We conjectured that the activity of some extracytoplasmic
      function (ECF) sigma factors, most of which are caught and regulated directly by
      cognate transmembrane anti-sigma factors, are affected by altered lipid
      composition of the membranes. Induction of the activities of ECF sigma factors
      (sigma(M) and sigma(V)) was observed after removal of IPTG, though that of
      sigma(V) was small. But other ECF sigma factors (sigma(W), sigma(X), sigma(Y),
      sigma(YlaC) and sigma(Z)) and the general stress sigmas sigma(B) and sigma(I)
      were not induced. Especially sigma(M) was activated strongly with the reduction
      of PG content and sustained a high level of activity, in contrast to the
      transient activation in PG normal cells after exposure to high salinity. This
      study demonstrates a new relationship between the alterations of lipid
      composition in the membranes and the activation of ECF sigma factors.

PMID- 19745568
TI  - Genomic and polyploid evolution in genus Avena as revealed by RFLPs of repeated
      DNA sequences.
AB  - Phylogenetic relationships and genome affinities were investigated by utilizing
      all the biological Avena species consisting of 11 diploid species (15
      accessions), 8 tetraploid species (9 accessions) and 4 hexaploid species (5
      accessions). Genomic DNA regions of As120a, avenin, and globulin were amplified
      by PCR. A total of 130 polymorphic fragments were detected out of 156 fragments
      generated by digesting the PCR-amplified fragments with 11 restriction enzymes.
      The number of fragments generated by PCR-amplification followed by digestion with
      restriction enzymes was almost the same as those among the three repeated DNA
      sequences. A high level of genetic distance was detected between A. damascena
      (Ad) and A. canariensis (Ac) genomes, which reflected their different morphology
      and reproductive isolation. The A. longiglumis (Al) and A. prostrata (Ap) genomes
      were closely related to the As genome group. The AB genome species formed a
      cluster with the AsAs genome artificial autotetraploid and the As genome diploids
      indicating near-autotetraploid origin. The A. macrostachya is an outbreeding
      autotetraploid closely related with the C genome diploid and the AC genome
      tetraploid species. The differences of genetic distances estimated from the
      repeated DNA sequence divergence among the Avena species were consistent with
      genome divergences and it was possible to compare the genetic intra- and inter
      ploidy relationships produced by RFLPs. These results suggested that the PCR
      mediated analysis of repeated DNA polymorphism can be used as a tool to examine
      genomic relationships of polyploidy species.

PMID- 19745569
TI  - A dominant mutation of TWISTED DWARF 1 encoding an alpha-tubulin protein causes
      severe dwarfism and right helical growth in rice.
AB  - Dwarfism is a common type of mutation in many plant species. The pathways and
      factors regulating biosynthesis and signaling of several plant growth regulators
      have been clarified through analyses of dwarf mutants in rice, Arabidopsis, pea,
      and maize. However, the genetic mechanisms controlling dwarfism are not well
      characterized, and the causal genes underlying most dwarf mutants are still
      uncovered. Here, we report a dominant mutant, Twisted dwarf 1-1 (Tid1-1), showing
      dwarfism and twisted growth in rice. Tid1-1 exhibit right helical growth of the
      leaves and stem and shortening of the roots. They also show an increased number
      of cells in the shoot apical meristem. Cells in the leaves of Tid1-1 are often
      ill-shapen, possibly owing to irregular cell division. Cell elongation in roots
      is suppressed in the elongation zone, and cells in the root apical meristem are
      enlarged. Map-based cloning of TID1 revealed that it encodes an alpha-tubulin
      protein comprising microtubules and is an ortholog of Arabidopsis LEFTY genes.
      Our analysis of the Tid1-1 mutant revealed that the dynamics of microtubules
      affects not only anisotropic growth in both dicots and monocots, but also
      meristematic activity and gross plant morphology.

PMID- 19745570
TI  - ENU induced single mutation locus on chr 16 leads to high-frequency hearing loss
      in mice.
AB  - The hallmark of age-related (presbycusis) and noise-induced hearing loss is high
      frequency (> 20 kHz) hearing loss. Through a collaborative study with TMGC
      (Tennessee Mouse Genome Consortium), seventeen ENU-induced mouse mutation strains
      with high-frequency hearing loss have been identified, but affected genes are yet
      identified. As a first step in identifying the gene/s underlying the ENU
      mutations, we created a F2 population between a representative mutation strain,
      118 TNE and a wild type strain, CAST/EJ (CAST). Phenotypic analysis showed that
      there is a 3:1 ratio of segregation between normal and hearing loss in the F2
      population, suggestion a single locus regulation. However, the linkage mapping
      identified 2 QTLs, each on chromosomes 15 and 16. Further statistical analysis of
      marker segregation patterns revealed that the locus on Chr 16 was ENU induced
      while the one on Chr 15 was derived from the parental strain, CAST.

PMID- 19745571
TI  - Comparative analysis of evolutionary modes in Mc1r coat color gene in wild mice
      and mustelids.
AB  - Sequences from ten species of Mus (Rodentia, Muridae) of the melanocortin-1
      receptor (Mc1r) gene (945 bp), which plays a key role in coat color
      determination, were compared with an existing Mc1r dataset (ca. 498 bp) from 12
      species of Mustela and Martes (Carnivora, Mustelidae). The dN/dS ratio (omega)
      was estimated at 0.19 for Mus and 0.35 for the mustelids, using a likelihood
      based one-ratio model with empirical codon frequencies. Running the model with
      equal codon frequencies gave a dramatic increase in omega for the mustelids
      (1.02) but not for Mus (0.31), indicating stronger codon usage bias in Mc1r among
      mustelids. When omega was estimated with the free-ratio model, significantly
      accelerated rates of amino acid replacement (nearly 1 in omega) were seen in
      several regions of the Mus phylogeny, such as in the ancestral subgeneric
      lineages, possibly associated with ecological niche shifting. Our results suggest
      that both functional constraints on coat color variation and selective
      constraints on codon usage bias have participated in structuring Mc1r gene
      sequences. Furthermore, they suggest that these contrasting influences have acted
      differentially in Mus and the mustelid lineages, and also differentially during
      the course of evolution within the genus Mus.

PMID- 19745572
TI  - Genotyping of the Q locus in wheat by a simple PCR-RFLP method.
AB  - The Q locus located on the long arm of chromosome 5A is a key factor in evolution
      and widespread cultivation of domesticated wheat. The Q locus pleiotropically
      affects many agronomically important traits including threshability, glume shape
      and tenacity, rachis fragility and others. Genotyping of the Q locus based on the
      complex traits is ambiguous due to their multi-genetic control through
      interactions with the Q locus. To determine the Q locus genotype of wheat
      accessions possessing A genome, we developed a method based on polymerase chain
      reaction - restriction fragment length polymorphism (PCR-RFLP) analysis. The Q
      and q alleles were clearly distinguished by PCR-RFLP analysis at six conserved
      single nucleotide polymorphisms in common wheat and wild and cultivated einkorn,
      emmer and timopheevi wheat. The Q locus genotype of Triticum sinskajae, which is
      one of the einkorn wheat species and exhibits free-threshing trait, was
      determined to be qq as expected. This simple PCR-RLFP-based genotyping method
      should serve as a useful tool in studying the origin of Q and thus wheat
      evolution after domestication and the following widespread cultivation.

PMID- 19745573
TI  - Cloning and tissue-specific expression of a delta-COP homologue in a freshwater
      and a brackish water-adapted strain of rainbow trout (Oncorhynchus mykiss).
AB  - In eukaryotic cells, intracellular transport is mediated by coated vesicular
      carriers. Coat proteins I (COPI) vesicles are involved in the retrograde
      transport from Golgi apparatus to the endoplasmic reticulum. The COPI complex is
      composed of ADP-ribosylation factor 1 and coatomer comprising seven subunits,
      termed alpha-zeta. We isolated and characterised a cDNA sequence from rainbow
      trout homolog to delta-subunit of COPI complex (delta-COP). Trout delta-COP gene
      encodes a protein of 509 aa including a characteristic Mu homology domain.
      Searches at the Ensemble Genome browser identified three additional teleostean
      delta-COP-like sequences from pufferfish, rice fish, and stickleback. Sequence
      identity of piscine delta-COP protein sequences is greater than 84%. Moreover, a
      phylogenetic analysis indicates that delta-COP protein sequences are strongly
      conserved among vertebrate species. delta-COP homologue is ubiquitously expressed
      in trout tissues. Quantitative Real-Time RT-PCR revealed that delta-COP is
      differentially expressed in liver and gill tissue of two rainbow trout strains,
      the freshwater strain STEELHEAD and the brackish water-adapted strain BORN.

PMID- 19745574
TI  - Microsatellite loci analysis for the genetic variability and the parentage test
      of five dog breeds in South Korea.
AB  - To investigate the population structure of five dog breeds in South Korea and to
      validate polymorphic microsatellite markers for the parentage test,
      microsatellite loci analyses were conducted for two Korean native dog breeds,
      Poongsan and Jindo, and three imported dog breeds, German Shepherd, Beagle and
      Greyhound. Overall genetic diversity was high across all dog breeds (expected
      heterozygosity range: 0.71 to 0.85), although breeds differed in deviations from
      Hardy-Weinberg equilibrium (HWE). Significant reduction of heterozygosity in the
      Poongsan and Greyhound breeds was caused by non-random mating and population
      substructure within these breeds (the Wahlund effects). The close relationship
      and high degree of genetic diversity for two Korean native dog breeds were
      substantial. The mean polymorphism information content value was highest in
      Jindos (0.82) and Poongsans (0.81), followed by Beagles (0.74), Greyhounds
      (0.72), and German Shepherds (0.66). Accumulated exclusion power values, as an
      indication of marker validity for parentage tests, were varied but very high
      across breeds, 0.9999 for Jindos, Poongsans, and Beagles, 0.9997 for Greyhounds,
      and 0.9995 for German Shepherds. Taken together, the microsatellite loci
      investigated in this study can serve as suitable markers for the parentage test
      and as individual identification to establish a reliable pedigree verification
      system of dog breeds in South Korea. This study also stresses that the population
      subdivision within breeds can become an important cause of deviation from HWE in
      dog breeds.

PMID- 19745575
TI  - Degradation kinetics of gamma-oryzanol in antioxidant-stripped rice bran oil
      during thermal oxidation.
AB  - Gamma-oryzanol, a group of phytosterol ferulates found in rice bran, possesses
      antioxidative activity and other bioactivities. The kinetics of thermal
      degradation of gamma-oryzanol in stripped rice bran oil (SRBO) were investigated
      under heating at 132, 160, 192 and 222 degrees C for 480, 140, 60 and 50 h,
      respectively. Losses of the overall gamma-oryzanol and its components
      (cycloartenyl ferulate, 24-methylene cycloartanyl ferulate, campesteryl ferulate
      and beta-sitosteryl ferulate) could be expressed by the first-order kinetics
      model. The rate constant of thermal degradation of gamma-oryzanol increased with
      increasing heating temperatures. The temperature dependence of the obtained rate
      constants was found to obey the Arrhenius equation. Campesteryl ferulate showed
      slightly more thermally resistant than other components at temperature lower than
      160 degrees C. However, the change in the absorbance from 2,2-diphenyl-1
      picrylhydrazyl (DPPH) assay as a function of heating time exhibited the same
      pattern for the SRBO with and without gamma-oryzanol for all studied heating
      temperatures.

PMID- 19745576
TI  - Utilization of waste crab shell (Scylla serrata) as a catalyst in palm olein
      transesterification.
AB  - Aquaculture activity has increased the population of crab, hence increasing the
      generation of related wastes, particularly the shell. In addition, the number of
      molting process in crabs compounds further the amount of waste shell generated.
      As such, in the present work, the application of the waste crab shell as a source
      of CaO in transesterification of palm olein to biodiesel (methyl ester) was
      investigated. Preliminary XRD results revealed that thermally activated crab
      shell contains mainly CaO. Parametric study has been investigated and optimal
      conditions were found to be methanol/oil mass ratio, 0.5:1; catalyst amount, 4
      wt. %; and reaction temperature, 338 K. As compared to laboratory CaO, the
      catalyst from waste crab shell performs well, thus creating another low-cost
      catalyst source for producing biodiesel as well as adding value to the waste crab
      shell. Reusability of crab shell CaO has also been studied and the outcome
      confirmed that the catalyst is capable to be reutilized up to 11 times, without
      any major deterioration.

PMID- 19745577
TI  - Optimization of enzymatic synthesis of palm-based kojic acid ester using response
      surface methodology.
AB  - Kojic acid monooleate is a fatty acid derivative of kojic acid which can be
      widely used as a skin whitening agent in a cosmetic applications. In avoiding any
      possible harmful effects from chemically synthesized product, the enzymatic
      synthesis appears to be the best way to satisfy the consumer demand nowadays. The
      ability of immobilized lipase from Rhizomucor meihei (lipozyme RMIM) to catalyze
      the direct esterification of kojic acid and oleic acid was investigated. Response
      Surface Methodology (RSM) and 5-level-4-factor central composite rotatable were
      employed to evaluate the effects of synthesis parameters such as enzyme amount
      (0.1-0.4 g), temperature (30-60 degrees C), substrate molar ratio (1-4 mmol,
      kojic acid:oleic acid) and reaction time (24-48 h) on percentage molar conversion
      to kojic acid monooleate. Analysis of the product using TLC, GC and FTIR showed
      the presence of kojic acid monooleate. The optimal conditions for the enzymatic
      reaction were obtained after analysis with backward elimination using 0.17 g of
      enzyme and 4 mmol of substrate at 52.50 degrees C for 42 h. Under these
      conditions the esterification percentage was 37.21%. The results demonstrated
      that response surface methodology can be applied effectively to optimize the
      lipase-catalysed synthesis of kojic acid monooleate. The optimum conditions can
      be used to scale up the process.

PMID- 19745578
TI  - Comparison of gamma-oryzanol contents in crude rice bran oils from different
      sources by various determination methods.
AB  - Although there are various determination methods for gamma -oryzanol contained in
      rice bran oil by absorptiometry, normal-phase HPLC, and reversed-phase HPLC,
      their accuracies and the correlations among them have not been revealed yet.
      Chloroform-containing mixed solvents are widely used as mobile phases in some
      HPLC methods, but researchers have been apprehensive about its use in terms of
      safety for the human body and the environment.In the present study, a simple and
      accurate determination method was developed by improving the reversed-phase HPLC
      method. This novel HPLC method uses methanol/acetonitrile/acetic acid (52/45/3
      v/v/v), a non-chlorinated solvent, as the mobile phase, and shows an excellent
      linearity (y = 0.9527x + 0.1241, R(2) = 0.9974) with absorptiometry. The mean
      relative errors among the existing 3 methods and the novel method, determined by
      adding fixed amounts of gamma-oryzanol into refined rice salad oil, were -4.7%
      for the absorptiometry, -6.8% for the existing normal-phase HPLC, +4.6% for the
      existing reversed-phase HPLC, and -1.6% for the novel reversed-phase HPLC method.
      gamma -Oryzanol content in 12 kinds of crude rice bran oils obtained from
      different sources were determined by the four methods. The mean content of those
      oils were 1.75+/-0.18% for the absorptiometry, 1.29+/-0.11% for the existing
      normal-phase HPLC, 1.51+/-0.10% for the existing reversed-phase HPLC, and 1.54+/
      0.19% for the novel reversed-phase HPLC method.

PMID- 19745579
TI  - Synthesis and properties of polycarboxylate-type green surfactants with S- or N
      linkages.
AB  - Polycarboxylate-type green surfactants with either sulfide- (S-) or imino- (N-)
      linkages were prepared in high yields by a single addition reaction of fatty
      mercaptan or fatty amine with unsaturated polycarboxylic acids such as fumaric,
      maleic, itaconic and aconitic acids. They exhibited surfactant properties and
      excellent biodegradabilities. Also, green surfactants with S-linkages showed
      better calcium ion sequestration abilities compared to the corresponding
      surfactant having an N-linkage. Among these surfactants, aconitic acid-derived
      polycarboxylate with an S-linkage exhibited calcium ion sequestration capacities
      similar to that of disodium 3-oxapentanedioate (ODA), a conventional calcium ion
      sequestrant on a molar basis of the surfactant.

PMID- 19745580
TI  - Removal of fluoride ion by bone char produced from animal biomass.
AB  - Bone char (BC) was prepared by carbonizing four types of animal biomass, and the
      adsorption of fluoride ions and elution of phosphate ions were investigated. It
      was found that the BC yield decreased as carbonization temperature increased, and
      that carbonization temperature had no significant effect on surface pH, base or
      acid consumptions. Fluoride ion adsorption was increased in BC produced at a low
      carbonization temperature. The adsorption mechanism of fluoride ion on BCs might
      be monolayer adsorption. BC can potentially be used to remove fluoride ions in
      drinking water. However, it was found that phosphate ions from BC are eluted due
      to adsorption of fluoride ions, and that ingestion of large amounts of phosphate
      ions inhibits reabsorption of calcium in the human body. Thus there is a need to
      study the elution behavior of phosphate ions. The adsorption mechanisms of
      fluoride ions onto BC would be a physical adsorption onto BC and phosphate ion in
      BC is exchanged to fluoride ion.

PMID- 19745581
TI  - Antioxidative capacities of durum wheat flour and its components on linoleic
      acid.
AB  - The antioxidative activities of durum wheat flour and its components on linoleic
      acid were examined at 50 degrees C and 12% relative humidity. The progress of the
      oxidation was monitored by the pressure change due to the oxygen consumption
      during the oxidation. The antioxidative capacities were assessed by the length of
      the induction period for the oxidation. Durum wheat flour and its methanol
      extract showed antioxidative capacities. Three kinds of gluten, i.e., durum wheat
      gluten, hard red winter wheat gluten, and hard red spring wheat gluten, also
      showed antioxidative capacities. On the other hand, wheat starch had no
      antioxidative capacity. The addition of durum wheat flour, its gluten or its
      methanol extract to linoleic acid lengthened the induction period depending on
      the amount of the additive.

PMID- 19745582
TI  - [Extraction method suitable for detection of unheated crustaceans including
      cephalothorax by ELISA].
AB  - When unheated whole samples of crustaceans (shrimp, prawn and crab) were analyzed
      with our ELISA kit (FA test EIA-Crustacean 'Nissui') using anti-tropomyosin
      antibodies, a remarkable reduction in reactivity was recognized. This reduction
      in activity was found to be due to the digestion of tropomyosin during the
      extraction process by proteases contained in cephalothorax. To avoid the
      digestion of tropomyosin by proteases, we developed an extraction method (heating
      method) suitable for the detection of tropomyosin in unheated crustaceans
      including cephalothorax. Experiments with unheated whole samples of various
      species of crustaceans confirmed that the heating method greatly improved the low
      reactivity in the standard method; the heating method gave extraction
      efficiencies of as high as 93-107%. Various processed crustaceans with
      cephalothorax, such as dry products (unheated or weakly heated products) and
      pickles in soy sauce (unheated products), that showed low reactivity with the
      standard method were confirmed to give superior results with the heating method.
      These results indicated that the developed heating method is suitable for
      detecting unheated crustaceans with cephalothorax by means of the ELISA kit.

PMID- 19745583
TI  - [Analysis of primary aromatic amines in paper products].
AB  - A highly sensitive analytical method for 25 kinds of primary aromatic amines and
      azo-dyes in paper products was developed. Free amines and total amines of the
      samples were analyzed. The amount of each azo-dye was calculated from the amount
      of total amines by subtracting the amount of free amines. Amines and azo-dyes
      were migrated into water at 23 degrees C for 24 hours. Free amines were extracted
      into dichloromethane after alkalization with sodium hydroxide solution. Azo-dyes
      were reduced to amines with sodium dithionite, alkalized, and then extracted into
      dichloromethane as total amines. They were determined by GC/MS. The recoveries of
      100 microg/kg amines spiked into migration solution were in the range of 69-122%,
      except for 4,4'-oxydianiline and 4,4'-diaminodiphenylmethane which gave recovery
      rates of approximately 40%. The determination limits of amines were 4-20
      microg/kg in paper. Amines and azo-dyes were surveyed in 17 kinds of base paper
      and 16 kinds of paper products for food contact use. Aniline was detected at
      levels of 4-20 microg/kg from most recycled papers, whereas the other amines were
      not detected in any sample.

PMID- 19745584
TI  - [Determination of illudin S in Omphalotus guepiniformis and foods that caused
      food poisoning by liquid chromatography with tandem mass spectrometry].
AB  - A simple method was developed for determination of illudin S in fungi (Omphalotus
      guepiniformis: poisonous mushroom) and a food that caused food poisoning, using
      liquid chromatography tandem mass spectrometry (LC/MS/MS). Illudin S in fungi and
      the food that caused food poisoning was extracted with methanol and then cleaned
      up with an Oasis HLB cartridge. LC separation was performed with an octadecylated
      silica column (Inertsil ODS-3, 2.1 mm i.d. x 150 mm) and a mobile phase of 0.1%
      formic acid-methanol (7 : 3) at a flow rate 0.2 mL/min. Mass spectral acquisition
      was performed in the positive mode and illudin S was targeted using multiple
      reaction monitoring (MRM) with electrospray ionization (ESI). The recoveries of
      illudin S were 84-94% from edible fungi (Lentinula edodes, Pleurotus ostreatus
      and Panellus serotinus). The detection limits of illudin S in the fungi (L.
      edodes, P. ostreatus and P. serotinus) were 0.08-0.10 microg/g respectively.
      Illudin S was detected in the food that caused food poisoning at the level of 2.0
      and 15.1 microg/g in the soup and fungi, respectively. The recovery of illudin S
      from a mushroom soup (cooked at 100 degrees C for 10 min) sample which simulated
      food poisoning was 74.8%. These results indicate that the developed method is
      suitable for the determination of illudin S in fungi (O. guepiniformis) and foods
      that caused food poisoning.

PMID- 19745585
TI  - Effect of nisin (Nisaplin) on the growth of Listeria monocytogenes in Karashi
      mentaiko (Red-pepper Seasoned Cod Roe).
AB  - The influence of Nisaplin, which contains 2.5% nisin, on the growth of Listeria
      monocytogenes in Karashi-mentaiko (red-pepper seasoned cod roe) was investigated.
      The MICs of Nisaplin for L. monocytogenes (10(8) CFU/mL) were measured; seven
      isolates showed a value of 1,600 microg/mL and one isolate showed a value of 800
      microg/mL. All L. monocytogenes isolates had a MIC of 800 microg/mL at 10(6)
      CFU/mL. The number of L. monocytogenes in Karashi-mentaiko stored at 4 degrees C
      was decreased by Nisaplin added at 60 and 600 microg/g. These results indicated
      that Nisaplin effectively inhibits the growth of L. monocytogenes in Karashi
      mentaiko.

PMID- 19745586
TI  - [Detection of wheat as an allergenic substance in models of processed foods by a
      nested PCR methods].
AB  - A polymerase chain reaction (PCR) method for verifying the allergen labeling of
      foods (i.e., the presence of wheat, buckwheat, or peanut) was adopted as the
      official Japanese identification test by the Ministry of Health, Labour and
      Welfare of Japan in 2002. We have verified the wheat labeling of several
      commercial food items by using the adopted PCR method. The study has revealed
      that some foods with positive results in the screening test yielded negative
      results in the identification test. When the result of the screening test
      disagrees with that of the identification test, the validation of food labeling
      is remarkably difficult. Therefore, we developed a nested PCR method with high
      sensitivity and specificity and employed this method in our routine testing as
      necessary. In this study, we examined 11 types of models of processed foods
      containing 10 microg/g wheat protein by using the adopted PCR and nested PCR
      methods; these samples were prepared by various processes and had varying
      physical properties. The adopted and nested PCR methods enabled the detection of
      wheat in 8 and 10 types of food models, respectively. The reasons for the failure
      in detecting the food allergens include DNA fragmentation due to the processing
      of food and the presence of DNA from other sources in the extracted DNA. In both
      PCR methods, an increase in the amount of template DNA in the PCR mixture enabled
      the detection of wheat DNA in all the food samples, but an excessive increase in
      the amount of template DNA hindered PCR amplification. These results indicate
      that an increase in the amount of template DNA increases the efficiency of the
      detection of allergens in processed foods by conventional PCR. Further
      investigation is needed to remove factors that inhibit PCR amplification of the
      extracted DNA.

PMID- 19745587
TI  - [Surveillance of perchlorate level in leafy vegetables and bottled water].
AB  - Perchlorate (ClO(4)(-)) is both a naturally occurring and artificial compound,
      and it inhibits iodide uptake into the thyroid gland and disturbs thyroid
      function. It has been detected in many foods in the United States. In order to
      investigate perchlorate contamination in foods in Japan, perchlorate level in 82
      leafy vegetable samples and 20 bottled mineral water samples was measured using a
      procedure based on the FDA's procedure, employing IC-MS/MS with (18)O(4)-labeled
      perchlorate as an internal standard. Among 82 leafy vegetable samples tested,
      perchlorate levels were under the LOQ (0.3 ng/g) in 3 samples and ranged from 0.3
      ng/g to 29.7 ng/g in 79 samples. In 20 bottled water samples, perchlorate was
      under the LOQ (0.1 ng/mL) in 14 samples and ranged from 0.14 ng/mL to 0.35 ng/mL
      in 6 samples.

PMID- 19745588
TI  - The reawakening of bendamustine - also in breast cancer?

PMID- 19745589
TI  - Adjuvant anthracyclines and taxanes: quantifying the costs of therapeutic
      advances in breast cancer.

PMID- 19745590
TI  - Doxorubicin and paclitaxel versus fluorouracil, doxorubicin and cyclophosphamide
      as first-line therapy for women with advanced breast cancer: long-term analysis
      of the previously published trial.
AB  - BACKGROUND: The aim of this study was to perform an independent review of the
      efficacy data and to determine whether the efficacy difference observed in a
      phase III randomised clinical trial that compared doxorubicin plus paclitaxel
      (AT) versus fluorouracil/doxorubicin/cyclophosphamide (FAC) in first-line
      chemotherapy of metastatic breast cancer was maintained after a longer follow-up
      period. MATERIAL AND METHODS: A blinded independent review of original
      radiological images and original case report forms (CRFs) was conducted by an
      expert radiologist and an expert medical oncologist, respectively. The analysis
      of the updated data included time to progression (TTP) and overall survival (OS).
      RESULTS: CRFs for all 267 patients randomised in the study were available for
      medical review. The results of the independent review were consistent with the
      original analysis. At a median follow-up of 69 months, the difference in median
      TTP and OS in favour of the AT arm remained significant (median TTP 8.1 vs. 6.2
      months, (p = 0.036); OS 23.0 vs. 18.3 months, (p = 0.005), respectively).
      CONCLUSIONS: This blinded independent review and analysis of updated data
      confirmed the advantage for AT over FAC with regard to TTP and OS in patients
      with metastatic breast cancer.

PMID- 19745591
TI  - Tolerability of dose escalation of ibandronate in patients with multiple myeloma
      and end-stage renal disease: a case series.
AB  - BACKGROUND: Bone disease is a feature of multiple myeloma (MM). Many patients
      have compromised renal function and sometimes develop end-stage renal disease
      (ESRD). For these patients, presently there exists no approved bisphosphonate,
      which is an elementary part of the standard therapeutic regimen of MM. PATIENTS
      AND METHODS: We evaluated the tolerability of ibandronate 2-6 mg every 4 weeks in
      patients with MM and ESRD receiving regular hemodialysis over 12 weeks (open
      label, single-center, observational study). Ibandronate pharmacokinetics were
      measured until the end of the next dialysis. Adverse events were recorded.
      RESULTS: 8 patients received ibandronate (average duration 5.6 months). Urinary
      excretion ranged from 0.15 to 341.9 microg/24 h. Mean ibandronate peak levels
      increased in a dose-dependent manner (2 mg: 141.4 +/- 67.0 ng/ml; 4 mg: 298.5 +/-
      82.0 ng/ ml; 6 mg: 564.3 +/- 318.9 ng/ml). No adverse events were reported.
      CONCLUSION: Based on these results and published bisphosphonate data, we have
      decided to offer off-label ibandronate treatment to MM patients receiving
      hemodialysis.

PMID- 19745592
TI  - Phase II STUdy with 3rd- or 4th-line bendamustine (flat dose) therapy in patients
      with metastatic breast cancer.
AB  - BACKGROUND: Bendamustine is a drug with a favorable side effect spectrum and it
      offers a chance to overcome tumor resistance in pretreated patients with
      metastatic breast cancer (MBC). PATIENTS AND METHODS: Bendamustine was given as
      flat dose with 200 mg at days 1 + 2 in MBC patients pretreated with 2-3 different
      chemotherapies. Therapy was repeated at day 28 or fully recovered neutrophils.
      After 2 treatment cycles, a tumor response evaluation was performed. Toxicity was
      graded according to the National Cancer Institute common toxicity criteria (NCI
      CTC) catalogue. RESULTS: 22 patients were evaluated for toxicity. 4 patients
      dropped out before the first tumor response evaluation; thus, 18 patients were
      evaluable for anticancer efficacy evaluation. 3/18 patients reached a partial
      remission (PR), 4 stable disease and 11 showed progression after 2 treatment
      cycles. The time to progression (TTP) was 5 months in patients with PR and 4
      months in patients with no change (NC). In patients with progressive disease
      (PD), TTP was < 2 months. The main toxicities were nausea, weight loss and
      fatigue. CONCLUSIONS: Bendamustine can be given with a fixed flat dose, which
      simplifies the drug preparation. 2/5th of all treated patients responded to this
      therapy whereas bendamustine showed no anticancer effect in 3/5th of all
      patients. Bendamustine is definitely a drug with anticancer potential.

PMID- 19745593
TI  - Impact of treatment guidelines and implementation of a quality assurance program
      on quality of care in endometrial cancer.
AB  - BACKGROUND: The treatment guidelines in the last decade have shown a trend
      towards increasing surgical radicality in endometrial cancer. Little information
      is available on the implementation of standards into clinical reality. We
      evaluated the adherence to standard therapy before and after introduction of an
      internal quality management system and determined the reasons for non-adherence.
      PATIENTS AND METHODS: A retrospective analysis of the inhouse tumor registry was
      performed. Included were all patients with Federation of Gynecology and
      Obstetrics (FIGO) I-III endometrial cancer and therapy at the Dr. Horst Schmidt
      Klinik (HSK) from 1997 to 2007. RESULTS: 206 patients with epithelial endometrial
      cancer in stage FIGO I-III underwent primary surgery at the HSK. 140 (68%)
      patients were operated as recommended by the guidelines. 20% of patients were
      operated less radically (17% vs. 22% before and after introduction of guidelines;
      p = 0.33) and 12% more radically. The latter was significantly reduced after
      implementation of quality management (21% vs. 7%; p = 0.004). Comorbidities and
      age played an important role in less-than-standard treatment. CONCLUSIONS:
      Adherence to guideline-based therapy for endometrial cancer can be achieved in
      most patients. Implementation of standards and quality assurance primarily helps
      to avoid surgical overtreatment but failed to reduce less-than-standard treatment
      radicality. The latter seemed to be more defined by patient characteristics than
      by institution standards.

PMID- 19745594
TI  - Primitive neuroectodermal tumor of the pelvis in an elderly patient.
AB  - BACKGROUND: Peripheral primitive neuroectodermal tumors (PNET) belong to the rare
      family of primary bone neoplasms. Recent clinicopathological studies have
      revealed that Ewing's sarcoma and PNET have overlapping features and they are now
      included in the same classification, the Ewing's sarcoma family of tumors (EFTs).
      PNET have a marked predilection for the extremities and are very rare in the
      pelvis. These tumors can occur at any age with a peak of incidence in the second
      and third decades but are very rare in patients over 40 years. CASE REPORT: We
      report the case of a 69-year-old man with PNET sarcoma. Outcome was favorable
      after combined modality treatment including chemotherapy based on the Memphis
      protocol - adapted from that used for Ewing's sarcoma in children - and surgery.
      CONCLUSION: Our case is uncommon because of the age at diagnosis, the fortuitous
      way of revelation, and the choice of dose-intense chemotherapy adapted from the
      Memphis protocol (cyclophosphamide- and doxorubicin-based) for children, which
      was efficient and safe. It supports the fact that an adult, and even an old
      patient, with good physical status, may be treated safely and radically even with
      dose-adapted aggressive chemotherapy.

PMID- 19745595
TI  - Treatment of a malignant peripheral nerve sheath tumor.
AB  - BACKGROUND: Malignant peripheral nerve sheath tumors (MPNST) are defined as any
      malignant tumor deriving from or differentiating into cells of the peripheral
      nerve sheaths, with a high risk of local recurrence and distant metastasis.
      Despite aggressive surgery and adjuvant therapy, the prognosis of MPNST is poor
      with reported 5-year survival rates of about 50%. CASE REPORT: We report a case
      of a patient with MPNST of the neck, who developed multiple thoracic metastases
      after a 14-year disease-free interval. The patient underwent a total of 4
      thoracic surgeries in the last 3 years because of local recurrence with tumor
      invasion to the chest wall and pericardium. Aggressive surgical intervention and
      adjuvant radiotherapy resulted in good outcome and long-term survival.
      CONCLUSION: Although MPNST is an aggressive carcinoma with poor survival,
      aggressive surgical intervention and radiotherapy resulted in good survival.

PMID- 19745596
TI  - Lymphoplasmacytic sclerosing pancreatitis with obstructive jaundice: a case
      report and review of the literature.
AB  - BACKGROUND: Lymphoplasmacytic sclerosing pancreatitis (LPSP) is a unique form of
      chronic pancreatitis and a tumor-like lesion simulating a carcinoma process
      clinically and radiographically. CASE REPORT: Herein, we presented a case of a
      patient with LPSP mimicking pancreatic carcinoma, who was admitted to our
      institution and subsequently treated with a Whipple procedure. This case typifies
      the growing awareness of this new clinicopathologic entity and the importance for
      LPSP to be included in the differential diagnosis of pancreaticobiliary disease.
      CONCLUSION: LPSP represents a diagnostic challenge which deserves more attention
      in the clinical management. An accurate preoperative diagnosis of LPSP can avoid
      pancreaticoduodenectomy in these patients.

PMID- 19745597
TI  - Radiofrequency ablation as a palliative treatment of primary liver sarcoma in an
      inoperable patient with hepatitis C virus-related cirrhosis.
AB  - BACKGROUND: Radiofrequency ablation (RFA) can be performed percutaneously, by
      laparotomy, or by laparoscopy. Recent advances in laparoscopic ultrasound (LUS)
      have improved the accuracy in detecting intrahepatic nodules. Primary liver
      sarcomas in chronic hepatitis C virus (HCV) infection with or without cirrhosis
      are extremely rare and the prognosis is poor. CASE REPORT: A 58-year-old man with
      a 5-year history of HCV-related Child-Pugh B cirrhosis was admitted with
      abdominal fullness, weight loss and lower-extremity edema lasting for 1 month.
      One mass lesion was measured as 4 cm in the segments 2 and 3 of the liver by
      abdominal computed tomography. As the patient's condition did not permit
      operation, he received LUS-guided RFA. After the treatment, the survival of this
      patient exceeded 48 months. RESULTS: Treatment of primary liver sarcomas arising
      in HCV infection with or without cirrhosis is primarily limited to surgery,
      chemotherapy and radiotherapy. Liver transplantation is not suggested for either
      primary or metastatic liver sarcoma. The described inoperable case is the only
      case report about a successful RFA treatment of a solitary liver sarcoma.
      CONCLUSION: We suggest that RFA can be considered as a choice of palliative
      treatment for primary liver sarcoma in inoperable patients with HCV-related
      cirrhosis.

PMID- 19745598
TI  - Precursor T-lymphoblastic lymphoma as a secondary malignancy in a young patient
      after successful treatment of acute promyelocytic leukemia.
AB  - BACKGROUND: Acute promyelocytic leukemia (APL) is a relatively rare subtype of
      acute myeloid leukemia. It has become the best curable subtype of acute leukemias
      in adults due to the inclusion of all-trans-retinoic acid (ATRA) in the
      treatment. Despite the efficacy of ATRA, chemotherapy must be added in APL
      patients in order to maintain durable complete remission. However, chemotherapy
      administration is inevitably related to many complications, including the risk of
      secondary malignancies. T-lymphoblastic lymphoma (T-LBL) is an infrequent disease
      that belongs to the group of highly aggressive lymphomas. CASE REPORT: The
      authors describe the case of a 25-year-old woman who was treated for APL in 2002
      and developed precursor T-LBL 5 years later. CONCLUSION: Several cases of
      secondary acute lymphoblastic leukemias in 'cured' APL patients have been
      described, but probably no patient with secondary precursor T-LBL. Secondary
      malignancy has become one of the topics discussed (not only) in APL patients. It
      is apparently related to the excellent treatment outcomes and long-term survival.
      Better tailored treatment based on relevant prognostic factors allowing
      chemotherapy reduction or omission in some patients is needed.

PMID- 19745599
TI  - Paraneoplastic humorally mediated hypercalcemia induced by parathyroid hormone
      related protein in gynecologic malignancies: a systematic review.
AB  - Humoral hypercalcemia of malignancy (HHM) is a metabolic phenomenon that is
      mediated by the paraneoplastic secretion of parathyroid hormone-related peptide
      (PTHrP). Gynecologic malignant neoplasms complicated by HHM have been reported
      for organs such as the uterus, cervix, ovary, vulva and the vagina. The purpose
      of our study was to perform a review of the published cases in the literature
      and, further, to identify parameters with effect on outcome. Among 34 women with
      gynecologic neoplasms, 22 suffered from ovarian and 6 from uterine malignancies,
      while 3 had vulvar and another 3 cervical cancer. Furthermore, clear cell
      carcinoma was the predominant histology associated with PTH-rP expression. A
      significant correlation was found between serum calcium and PTH-rP levels.
      Treatment of hypercalcemia was successful in all cases; pamidronate was utilized
      in 8 patients. Ovarian cancer patients with severe hypercalcemia and high PTH-rP
      serum levels had shorter survival compared to their counterparts with mild
      hypercalcemia or moderately elevated PTH-rP serum levels, but the differences
      were not statistically significant.

PMID- 19745600
TI  - The roles of glycosphingolipids in the proliferation and neural differentiation
      of mouse embryonic stem cells.
AB  - Glycosphingolipids including gangliosides play important regulatory roles in cell
      proliferation and differentiation. UDP-glucose:ceramide glucosyltransferase
      (Ugcg) catalyze the initial step in glycosphingolipids biosynthesis pathway. In
      this study, Ugcg expression was reduced to approximately 80% by short hairpin
      RNAs (shRNAs) to evaluate the roles of glycosphingolipids in proliferation and
      neural differentiation of mouse embryonic stem cells (mESCs).
      HPTLC/immunofluorescence analyses of shRNA- transfected mESCs revealed that
      treatment with Ugcg-shRNA decreased expression of major gangliosides, GM3 and
      GD3. Furthermore, MTT and Western blot/immunofluorescence analyses demonstrated
      that inhibition of the Ugcg expression in mESCs resulted in decrease of cell
      proliferation (P<0.05) and decrease of activation of the ERK1/2 (P<0.05),
      respectively. To further investigate the role of glycosphingolipids in neural
      differentiation, the embryoid bodies formed from Ugcg-shRNA transfected mESCs
      were differentiated into neural cells by treatment with retinoic acid. We found
      that inhibition of Ugcg expression did not affect embryoid body (EB)
      differentiation, as judged by morphological comparison and expression of early
      neural precursor cell marker, nestin, in differentiated EBs. However, RT
      PCR/immunofluorescence analyses showed that expression of microtubule-associated
      protein 2 (MAP-2) for neurons and glial fibrillary acidic protein (GFAP) for
      glial cells was decreased in neural cells differentiated from the shRNA
      transfected mESCs. These results suggest that glycosphingolipids are involved in
      the proliferation of mESCs through ERK1/2 activation, and that glycosphingolipids
      play roles in differentiation of neural precursor cells derived from mESCs.

PMID- 19745601
TI  - Optimization of Streptomyces bacteriophage phi C31 integrase system to prevent
      post integrative gene silencing in pulmonary type II cells.
AB  - phi C31 integrase has emerged as a potent tool for achieving long-term gene
      expression in different tissues. The present study aimed at optimizing elements
      of phi C31 integrase system for alveolar type II cells. Luciferase and beta
      galactosidase activities were measured at different time points post
      transfection. 5-Aza-2'deoxycytidine (AZA) and trichostatin A (TSA) were used to
      inhibit DNA methyltransferase and histone deacetylase complex (HDAC)
      respectively. In A549 cells, expression of the integrase using a CMV promoter
      resulted in highest integrase activity, whereas in MLE12 cells, both CAG and CMV
      promoter were equally effective. Effect of polyA site was observed only in A549
      cells, where replacement of SV40 polyA by bovine growth hormone (BGH) polyA site
      resulted in an enhancement of integrase activity. Addition of a C-terminal SV40
      nuclear localization signal (NLS) did not result in any significant increase in
      integrase activity. Long-term expression studies with AZA and TSA, provided
      evidence for post-integrative gene silencing. In MLE12 cells, both DNA methylases
      and HDACs played a significant role in silencing, whereas in A549 cells, it could
      be attributed majorly to HDAC activity. Donor plasmids comprising cellular
      promoters ubiquitin B (UBB), ubiquitin C (UCC) and elongation factor 1 alpha (EF1
      alpha) in an improved backbone prevented post-integrative gene silencing. In
      contrast to A549 and MLE12 cells, no silencing could be observed in human
      bronchial epithelial cells, BEAS-2B. Donor plasmid coding for murine
      erythropoietin under the EF1 alpha promoter when combined with phi C31 integrase
      resulted in higher long-term erythropoietin expression and subsequently higher
      hematocrit levels in mice after intravenous delivery to the lungs. These results
      provide evidence for cell specific post integrative gene silencing with C31
      integrase and demonstrate the pivotal role of donor plasmid in long-term
      expression attained with this system.

PMID- 19745602
TI  - LIN28B confers radio-resistance through the posttranscriptional control of KRAS.
AB  - To screen the differentially expressed microRNAs related to radio-resistance, we
      compared the microRNA profiles of lung cancer cells with different responses to
      ionizing radiation (IR). Of 328 microRNAs in microarray, 27 microRNAs were
      differentially expressed in NCI-H460 (H460) and NCI-H1299 (H1299) cells. Among
      them, let-7g was down-regulated in radio-resistant H1299 cells, and the level of
      let-7g was higher in radio-sensitive cells like Caski, H460, and ME180 in qRT-PCR
      analysis than in radio-resistant cells like A549, H1299, DLD1, and HeLa. Over
      expression of let-7g in H1299 cells could suppress the translation of KRAS, and
      increase the sensitivity to IR. When we knockdown the expression of LIN28B, an
      upstream regulator of let-7g, the level of mature let-7g was increased in H1299
      cells and the sensitivity to IR was also enhanced in LIN28B knockdown cells. From
      these data, we suggest that LIN28B plays an important role in radiation responses
      of lung cancer cells through inhibiting let-7g processing and increasing
      translation of KRAS.

PMID- 19745603
TI  - Fibroblasts in three dimensional matrices: cell migration and matrix remodeling.
AB  - Fibroblast-collagen matrix culture has facilitated the analysis of cell
      physiology under conditions that more closely resemble an in vivo-like
      environment compared to conventional 2-dimensional (2D) cell culture.
      Furthermore, it has led to significant progress in understanding reciprocal and
      adaptive interactions between fibroblasts and the collagen matrix, which occur in
      tissue. Recent studies on fibroblasts in 3-dimensional (3D) collagen matrices
      have revealed the importance of biomechanical conditions in addition to
      biochemical cues for cell signaling and migration. Depending on the surrounding
      mechanical conditions, cells utilize specific cytoskeletal proteins to adapt to
      their environment. More specifically, cells utilize microtubule dependent
      dendritic extensions to provide mechanical structure for matrix contraction under
      a low cell-matrix tension state, whereas cells in a high cell-matrix tension
      state utilize conventional acto-myosin activity for matrix remodeling. Results of
      collagen matrix contraction and cell migration in a 3D collagen matrix revealed
      that the use of appropriate growth factors led to promigratory and procontractile
      activity for cultured fibroblasts. Finally, the relationship between cell
      migration and tractional force for matrix remodeling was discussed.

PMID- 19745604
TI  - Expression of 4-1BB and 4-1BBL in thymocytes during thymus regeneration.
AB  - 4-1BB, a member of the tumor necrosis factor receptor (TNFR) superfamily, is a
      major costimulatory receptor that is rapidly expressed on the surface of CD4(+)
      and CD8(+) T cells after antigen- or mitogen-induced activation. The interaction
      of 4-1BB with 4-1BBL regulates immunity and promotes the survival and expansion
      of activated T cells. In this study, the expression of 4-1BB and 4-1BBL was
      examined during regeneration of the murine thymus following acute
      cyclophosphamide- induced involution. Four-color flow cytometry showed that 4-1BB
      and 4-1BBL were present in the normal thymus and were preferentially expressed in
      the regenerating thymus, mainly in CD4(+)CD8(+) double-positive (DP) thymocytes.
      Furthermore, the CD4(lo)CD8(lo), CD4(+)CD8(lo) and CD4(lo)CD8(+) thymocyte
      subsets, representing stages of thymocyte differentiation intermediate between DP
      and single-positive (SP) thymocytes, also expressed 4-1BB and 4-1BBL during
      thymus regeneration but to a lesser degree. Interestingly, the 4-1BB and 4-1BBL
      positive cells among the CD4(+)CD8(+) DP thymocytes present during thymus
      regeneration were TCR(hi) and CD69(+) unlike the corresponding controls.
      Moreover, the 4-1BB and 4-1BBL positive cells among the intermediate subsets
      present during thymus regeneration also exhibited TCR(hi/int+) and CD69(+/int)
      phenotypes, indicating that 4-1BB and 4-1BBL are predominantly expressed by the
      positively selected population of the CD4(+)CD8(+) DP and the intermediate
      thymocytes during thymus regeneration. RT-PCR and Western blot analyses confirmed
      the presence and elevated levels of 4-1BB and 4-1BBL mRNA and protein in
      thymocytes during thymus regeneration. We also found that the interaction of 4
      1BB with 4-1BBL promoted thymocyte adhesion to thymic epithelial cells. Our
      results suggest that 4-1BB and 4-1BBL participate in T lymphopoiesis associated
      with positive selection during recovery from acute thymic involution.

PMID- 19745605
TI  - Activation of PPAR gamma induces profound multilocularization of adipocytes in
      adult mouse white adipose tissues.
AB  - We sought to determine the effects of activation of peroxisome proliferator
      activated receptor-gamma (PPAR-gamma) on multilocularization of adipocytes in
      adult white adipose tissue (WAT). Male C57BL/6 normal, db/db, and ob/ob mice were
      treated with agonists of PPAR-gamma, PPAR-alpha, or beta(3)-adrenoceptor for 3
      weeks. To distinguish multilocular adipocytes from unilocular adipocytes, whole-
      mounted adipose tissues were co-immunostained for perilipin and collagen IV. PPAR
      gamma activation with rosiglitazone or pioglitazone induced a profound change of
      unilocular adipocytes into smaller, multilocular adipocytes in adult WAT in a
      time-dependent, dose-dependent, and reversible manner. PPAR-alpha activation with
      fenofibrate did not affect the number of locules or remodeling. db/db and ob/ob
      obese mice exhibited less multilocularization in response to PPAR-gamma
      activation compared to normal mice. Nevertheless, all adipocytes activated by
      PPAR-gamma contained a single nucleus regardless of locule number. Multilocular
      adipocytes induced by PPAR-gamma activation contained substantially increased
      mitochondrial content and enhanced expression of uncoupling protein-1, PPAR-gamma
      coactivator-1-alpha, and perilipin. Taken together, PPAR-gamma activation induces
      profound multilocularization and enhanced mitochondrial biogenesis in the
      adipocytes of adult WAT. These changes may affect the overall function of WAT.

PMID- 19745606
TI  - Cross-talk between BubR1 expression and the commitment to differentiate in
      adipose-derived mesenchymal stem cells.
AB  - BubR1 mitotic checkpoint kinase monitors attachment of microtubules to
      kinetochores and links regulation of the chromosome-spindle attachment to mitotic
      checkpoint signaling. Defects in BubR1-mediated signaling severely perturb
      checkpoint control and are linked to diseases such as cancer. Studies using BubR1
      mouse models suggest that BubR1 activities prevent premature aging and
      infertility. In this study, we show that BubR1 depletion in human adipose-derived
      mesenchymal stem cells (ASCs) precedes loss of the differentiation potential and
      induction of replicative senescence. These effects occur independently of
      p16(INK4A) expression and may involve DNA methylation. Our results reveal a new
      and unsuspected feature of BubR1 expression in regulation of adult stem cell
      differentiation.

PMID- 19745607
TI  - The presence of CD8+ invariant NKT cells in mice.
AB  - Invariant natural killer T (iNKT) cells develop in the thymus upon recognition of
      CD1d expressed on developing thymocytes. Although CD4 and CD8 coreceptors are not
      directly involved in the interaction between CD1d and the T cell receptors (TCRs)
      of iNKT cells, a conspicuous lack of CD8(+) iNKT cells in mice raised the
      question of whether CD8(+) iNKT cells are excluded due to negative selection
      during their thymic development, or if there is no lineage commitment for the
      development of murine CD8(+) iNKT cells. To address this question, we analyzed
      iNKT cell-specific TCR V alpha 14(+) transgenic mice, where the V alpha 14
      transgene forces the generation of iNKT cells. This allows detailed study of the
      iNKT cell repertoire. We were able to identify CD8(+) iNKT cells which respond to
      the NKT cell-specific glycolipid ligand alpha-galactosylceramide. Unlike
      conventional iNKT cells, CD8(+) iNKT cells produce predominantly IFN-gamma but
      not IL-4 upon antigen stimulation. We also confirmed the presence of CD8(+) iNKT
      cells in wild type mice. Our results suggest that CD8(+) NKT cells do exist in
      mice, although their population size is quite small. Their Th1-skewed phenotype
      might explain why the population size of this subtype needs to be controlled
      tightly.

PMID- 19745608
TI  - Does poly-N-acetyl glucosamine patch use reduce arteriovenous fistula and graft
      failure rates in hemodialysis patients with end-stage renal disease?
AB  - BACKGROUND: Maintenance of functional vascular access is crucial for the delivery
      of hemodialysis. The SyvekPatch is a topical marine microalgal poly-N-acetyl
      glucosamine hemostat approved by the Food and Drug Administration for use in the
      local management of bleeding wounds, such as vascular site, percutaneous
      catheters or tubes, and surgical debridement. METHODS: The Preservation of
      Vascular Access Study was designed to investigate the effectiveness of patch use
      in reducing failure rates of arteriovenous fistulas or grafts. Data from medical
      records of patients who received hemodialysis from January 2001 to December 2005
      at local ambulatory outpatient hemodialysis units in Charleston, South Carolina
      were analyzed. To explore whether greater use of the poly-N-acetyl glucosamine
      patch resulted in more favorable outcomes, patients were categorized into no
      patch use (n = 183) or 2 groups involving patch use, <70% of hemodialysis
      sessions (n = 88) or >or=70% of hemodialysis sessions (n = 64). The outcome
      measure was failure of access site estimated using Poisson regression models.
      RESULTS: Three hundred thirty-five patients (54% women) with 178 fistulas (44%)
      and 227 grafts (56%) were included. The study population was predominantly
      African American (84%), with a median age of 58 years. The adjusted relative rate
      of access failure involving patch use in <70% of hemodialysis sessions versus no
      patch use was 0.84 (95% CI, 0.37-1.94), and for patch use in >or=70% of
      hemodialysis sessions versus no patch use was 0.40 (95% CI, 0.16-1.02; trend P =
      0.045). CONCLUSIONS: The Preservation of Vascular Access Study results are
      consistent with improved access survival with frequent patch use. The application
      of patch in this population is a simple, well-accepted intervention and warrants
      further investigation.

PMID- 19745609
TI  - Nonalcoholic Fatty liver disease and metabolic syndrome in hypopituitary
      patients.
AB  - BACKGROUND: Increased incidence of cardiovascular mortality and nonalcoholic
      fatty liver disease (NAFLD) has been reported in hypopituitarism, but previous
      studies did not correct for obesity in these patients. Therefore, it remained
      unclear if endocrine deficiency in hypopituitarism is associated with metabolic
      consequences independent of obesity. This study was designed to determine the
      burden of cardiovascular disease and NAFLD in hypopituitarism. METHODS: We
      performed a retrospective case-control analysis of hypopituitary patients at
      Veterans Affair Medical center, Memphis, from January 1997 to June 2007. After
      matching for age, gender, obesity, and race, relevant data were abstracted from
      the subjects' records to determine the presence of hypopituitarism,
      cardiovascular risk factors, and fatty liver disease. Cases and controls were
      characterized by descriptive statistics and compared using chi(2) and Student t
      tests. RESULTS: Hypopituitary patients exhibited higher prevalence of
      hypertension- 88% versus 78% (P < 0.03), hypertriglyceridemia-80% versus 70% (P =
      0.05), low high-density lipoprotein cholesterol-84% versus 70% (P < 0.001), and
      metabolic syndrome-90% versus 71% (P < 0.001). Patients also had higher mean
      plasma glucose levels-228 +/- 152 versus 181 +/- 83 mg/dL (P < 0.01). Despite
      higher preponderance of cardiovascular risk factors in hypopituitary patients,
      prevalence of cardiovascular morbidity was similar in both groups (P > 0.3).
      Hypopituitary patients had higher elevations in serum aminotransferase levels and
      hyperbilirubinemia-24% versus 11% (P < 0.01), as well as higher international
      normalized ratio (INR) and hypoalbuminemia 40% versus 23% (P < 0.01).
      CONCLUSIONS: There is an increased prevalence of metabolic syndrome and liver
      dysfunction consistent with NAFLD in hypopituitarism. Although hypopituitary
      patients had higher prevalence of cardiovascular risk factors than controls, they
      were not disproportionately affected by cardiovascular disease.

PMID- 19745610
TI  - Effects of (-)doxazosin on histomorphologic and cell apoptotic changes of the
      hyperplastic prostate in castrated rats.
AB  - BACKGROUND: (-)Doxazosin is one of the enantiomers of (+/-)doxazosin, and it was
      reported that (-)doxazosin possessed higher selectivity for lower urinary tract
      between the cardiovascular system and the urinary system in the animal
      experiments in comparison with that of (+/-)doxazosin and (+)doxazosin.
      Therefore, it is important to know whether (-)doxazosin has a therapeutic effect
      on the hyperplastic prostate. METHODS: (-)Doxazosin and (+/-)doxazosin were
      administered intragastrically to prostatic hyperplasia rats, induced by
      testosterone propionate for 4 weeks, and each experimental group contained 8
      animals. The histomorphologic changes of the prostate were observed under light
      microscope, the quantitative analysis of the prostatic glandular cavity was
      performed using an image analysis system, and the cell apoptosis was detected by
      using flow cytometry. RESULTS: In comparison with model-control group, the volume
      index of the prostate in (-)doxazosin 3.0 mg/kg group became significantly
      smaller. The maximal diameter, perimeter, and area of the hyperplastic prostate
      glandular cavity, and the glandular epithelial cell height in (-)doxazosin (0.3,
      1.0, and 3.0 mg/kg) groups and (+/-)doxazosin group were significantly reduced. (
      )Doxazosin and (+/-)doxazosin did not significantly affect cell cycle
      distribution and cell proliferation index of the hyperplastic prostate. However,
      apoptotic rates of the prostatic cells in (-)doxazosin (0.3, 1.0, and 3.0 mg/kg)
      groups and (+/-)doxazosin group were significantly increased in comparison with
      those of model-control group. CONCLUSIONS: Both (-)doxazosin and (+/-)doxazosin
      inhibit the prostatic hyperplasia induced by testosterone propionate in castrated
      rats. The induction of prostate cell apoptosis might be one of the mechanisms
      underlying the therapeutic role of (-)doxazosin.

PMID- 19745611
TI  - Troisier's sign in renal failure.

PMID- 19745612
TI  - Disseminated histoplasmosis presenting as granulomatous epididymo-orchitis.
AB  - Genital involvement is an unusual manifestation of histoplasmosis. We report a
      case of histoplasmosis presenting as granulomatous epididymo-orchitis and review
      4 cases reported in the literature. Diagnosis of this infection is suggested by a
      compatible clinical picture and results of specific serology or antigen testing,
      but confirmation ultimately requires analysis of pathologic specimens. Surgical
      drainage or resection of involved tissues and systemic antifungals typically
      result in resolution of infection and improved outcomes.

PMID- 19745613
TI  - Devic's syndrome as initial presentation of systemic lupus erythematosus.
AB  - BACKGROUND: Devic's syndrome or neuromyelitis optica (NMO) is an inflammatory
      demyelinating disease of the central nervous system associated with optic
      neuritis, myelitis involving 3 or more contiguous spinal cord segments, and
      seropositivity for NMO-IgG antibody. CASE: A 22-year-old African American woman
      P1G0 at 22 weeks of gestation presented with weakness for 1 week. The weakness
      initially started in the left lower extremity and then involved the other
      extremities. She also had horizontal diplopia, temporal headache, and
      arthralgias. On physical examination, she had a discoid rash behind the left ear,
      muscle strength 3/5 in the upper and 0/5 in the lower extremities, and
      hyporeflexia. She had lymphopenia, a highly positive antinuclear antibody, and SS
      A/ SS-B antibodies. The magnetic resonance imaging of the patient showed abnormal
      cord signal within brain and cervical and thoracic spine. Salivary gland biopsy
      revealed mild lymphoplasmacytic inflammation. The NMO antibody was positive. A
      diagnosis of Devic's syndrome associated with probable systemic lupus
      erythematosus (SLE) was made. She was treated with pulse IV solumedrol and
      plasmapheresis for 4 days. The patient improved clinically with treatment, but
      the fetus developed bradycardia, which was treated with IV dexamethasone.
      DISCUSSION AND CONCLUSION: There is a debate about the relationship of NMO with
      autoimmune disorders, such as SLE or Sjogren syndrome. If clinically evident SLE
      or Sjogren or positive autoantibodies coexist with NMO signs and symptoms, the
      neurologic process could be an independent association due to NMO or may be a
      vasculitic complication of the systemic disease. Our case highlights these
      issues, difficulty in making a correct diagnosis, and choosing the appropriate
      management. Further case studies are needed to explore these important issues.

PMID- 19745614
TI  - A B-cell lymphoma diagnosed in "floater" tissue: implications of the diagnosis
      and resolution of a laboratory error.
AB  - Contamination of a paraffin-embedded tissue block with another patient's tissue
      can lead to an incorrect diagnosis. We report the use of short tandem repeats for
      the analysis of DNA extracted from microdissected tissue from unstained slides
      prepared from a decalcified block from a 33-year-old woman who was previously
      diagnosed with a low-grade B-cell lymphoma. This diagnosis was based on a single
      fragment of tissue found among bone fragments taken during orthopedic surgery at
      a referring hospital. Our results confirm that the B-cell lymphoma tissue was not
      derived from our patient. Furthermore, we suggest that in cases for which the
      definitive identification of a tissue contaminant can resolve clinically,
      therapeutically, and prognostically significant questions, short tandem repeat
      analysis of DNA derived from microdissected surgical pathology samples should be
      considered to minimize errors and enhance the quality of care.

PMID- 19745617
TI  - OASIS-C: hope for assessments that are clinically accurate and useful.

PMID- 19745618
TI  - Pandemic influenza preparedness planning in the home care environment.

PMID- 19745619
TI  - Benefits of hospice and palliative care certification.

PMID- 19745620
TI  - Research on prevention of urinary incontinence and catheter management.

PMID- 19745621
TI  - Dance of the home health visit: a step in the right direction.

PMID- 19745622
TI  - Depression and suicide risks in older adults: a case study.
AB  - Depression and suicide are significant problems encountered by home health
      clinicians caring for older, homebound individuals. Mr. F. was an 85-year-old
      retired police officer who was assessed to be at significant risk for suicide
      after his wife's death. The following case study outlines the Home Based Primary
      Care team's successful interdisciplinary treatment plan to reduce Mr. F.'s
      suicide risk.

PMID- 19745624
TI  - HEALTH COACHING: a fresh, new approach to improve quality outcomes and compliance
      for patients with chronic conditions.
AB  - Health coaching, its origin from motivational interviewing, enhances patient self
      management of chronic conditions by improving patient compliance and outcomes,
      and reducing costs. How health coaching has achieved this success and why
      traditional patient teaching has fallen short is explored. Dr. William Miller, an
      originator of the motivational interviewing concept, also shares his insights and
      thoughts in a brief question and answer session with the author.

PMID- 19745626
TI  - Transitions in home care.

PMID- 19745627
TI  - VNAs embrace accountability: providing, measuring, and reporting community
      benefits.

PMID- 19745628
TI  - Perspectives on autonomy.
AB  - This department, sponsored by the AONE, presents information to assist nurse
      leaders in shaping the future of healthcare through creative and innovative
      leadership. The strategic priorities of AONE anchor the editorial content. They
      reflect contemporary healthcare and nursing practice issues that challenge nurse
      executives as they strive to meet the needs of patients. This article describes
      how 9 Magnet-hospital, chief nursing officers perceive their autonomy and its
      importance in accomplishing their work.

PMID- 19745630
TI  - Putting it altogether: improving performance in heart failure outcomes, part 2.
AB  - As systems evolve over time, their natural tendency is to become increasingly
      more complex. Studies in the field of complex systems have generated new
      perspectives on management in social organizations such as hospitals. Much of
      this research appears as a natural extension of the cross-disciplinary field of
      systems theory. This is the 10th in a series of articles applying complex systems
      science to the traditional management concepts of planning, organizing,
      directing, coordinating, and controlling. As follow-up to the case study in this
      column's June 2009 article, this article highlights the interventions and
      outcomes of the study.

PMID- 19745631
TI  - Time out.
AB  - This biannual department, sponsored by the Council on Graduate Education for
      Administration in Nursing (CGEAN), provides information updates to nurse leaders
      on educational trends, issues, and research important for effective health system
      administration. The CGEAN Web site can be accessed at http://www.cgean.org.

PMID- 19745632
TI  - Improving patient-provider communication: a call to action.

PMID- 19745633
TI  - Nurse labor data: the collection and interpretation of nurse-to-patient ratios.
AB  - Nurse labor has been shown to be related to some patient outcomes, but varying
      definitions and measurement approaches have resulted in conflicting findings
      about the nature of the relationship. Nurse administrators and researchers need
      to know rates of missing data and error in labor data to better inform decision
      making. The authors compare the degree of completeness and the agreement between
      these approaches (nurse survey and nurse-to-patient ratio staffing plans) to
      obtain patient-to-nurse ratios at the unit level.

PMID- 19745634
TI  - Implementing an "always practice" to redefine skin care management.
AB  - With a nosocomial pressure ulcer rate higher than national benchmarks, leaders
      convened a quality improvement team to address the issue. The authors discuss the
      implementation of a new skin "always practice" initiative across the continuum of
      care and its outcomes.

PMID- 19745635
TI  - Care management redesign: increasing care manager time with patients and
      providers while improving metrics.
AB  - In many hospitals, addressing increasing financial and regulatory requirements
      has resulted in a decline in care managers' time spent communicating directly
      with patients, families, and healthcare providers. The authors discuss the
      redesign of a hospital care management model that increased the time care
      managers spend with patients, families, and other care professionals, while
      patient satisfaction increased, labor cost remained neutral, length of stay
      decreased, and the payment denial rate remained among the country's lowest.

PMID- 19745636
TI  - The content and context of change of shift report on medical and surgical units.
AB  - OBJECTIVE: This study was conducted to describe the current content and context
      of change of shift report (CoSR) on medical and surgical units and explore
      whether nurses use computerized support during the CoSR process. BACKGROUND:
      Change of shift report is a commonly occurring handoff that could contribute to
      gaps in care. METHODS: Bedside, face-to-face, and audiotaped CoSRs were
      audiotaped and observed on 7 medical and surgical units in 3 acute care
      facilities in the Western United States. RESULTS: Conventional content analysis
      revealed 4 themes: the Dance of Report, Just the Facts, Professional Nursing
      Practice, and Lightening the Load. Observations exposed the lack of content
      structure, high noise levels, interruptions, and no use of electronic health
      records in these facilities as a part of the report process. CONCLUSION:
      Improvements to CoSR include determining a consistent and tailored structure for
      report, evaluating types of report suitable for particular units, reducing
      interruptions and noise, and determining content amenable to computerization.

PMID- 19745637
TI  - Planning and creating a new bi-state nursing workforce center through unique
      partnerships.
AB  - Multiple strategies are needed to address the complex issues related to the
      nursing shortage. It is not enough to focus on increasing the number of students
      in the pipeline unless this is met with complimentary work to improve the
      professional practice environments of nursing staff. In addition, nurse-driven
      improvement projects that address specific patient and organizational outcomes
      will elevate the role of nurses from trusted professional to quality agents. The
      authors describe a partnership that has launched a new type of workforce center
      with core missions to create work environment improvements and point-of-care
      change led by staff nurses.

PMID- 19745638
TI  - The cart before the horse? Health insurance reform before health care reform.

PMID- 19745639
TI  - Does level of care, sex, age, or choice of drug influence adherence to treatment
      with antipsychotics?
AB  - Rates of nonadherence during treatment with antipsychotics have been found to
      vary in a wide range from 20% to 90%. The aim of the present study was to
      investigate the influence of inpatient versus outpatient status on the adherence
      to treatment with olanzapine and clozapine. In the period from 1999 to 2007,
      olanzapine and clozapine were the 2 most frequently analyzed antipsychotics at
      the Department of Clinical Pharmacology at St. Olavs University Hospital,
      Trondheim, Norway, with more than 24,000 and more than 18,000 samples,
      respectively. In total, 111 patients on olanzapine and 95 patients on clozapine
      had provided samples in both the inpatient and outpatient settings and were
      included in the study. The primary outcome variable was the serum concentration
      to-dose ratio (C/D ratio), that is, the serum drug concentration per milligram of
      drug given. For olanzapine, the C/D ratio in the outpatient setting was 10.7%
      lower than in the inpatient setting (P = 0.013). No such difference was found for
      clozapine. The difference in the olanzapine group was exclusively attributed to a
      lower outpatient ratio in females. For clozapine, no sex influence was found. No
      effect of age on the C/D ratios was found either for olanzapine or for clozapine.
      The lower C/D ratio in females using olanzapine in the outpatient setting might
      imply that they, in contrast to males, are less adherent to their medication when
      outside hospital. For clozapine, there were no indications of differences in
      adherence between inpatients and outpatients.

PMID- 19745640
TI  - Effects of aripiprazole on insight and subjective experience in individuals with
      an at-risk mental state.
AB  - INTRODUCTION: Although medication with antipsychotic for the psychosis prodrome
      has often caused some ethical issues, recent studies have shown that some novel
      antipsychotics are safer and more tolerable for young people. This study aimed to
      investigate whether the administration of aripiprazole would not only relieve the
      prodromal symptoms but also be tolerable for prodromal subjects and to evaluate
      the effect of medication on improvements in insight and subjective well-being.
      METHODS: The Structured Interview for Prodromal Syndromes was performed for
      patients identified as having the psychosis prodrome. Psychiatric measures
      included the Scale of Prodromal Symptoms. Clinical insight was measured using the
      Scale to Assess Unawareness of Mental Disorder, and changes in subjective
      experience were assessed using the Subjective Well-being Under Neuroleptics,
      Short version. The time frame was the first 8 weeks after beginning study
      medication. RESULTS: Thirty-six treatment-seeking prodromal patients (men, 42%;
      mean [SD] age, 23.4 [5.6] years) were enrolled. At the 12-week follow-up point,
      30 participants (83%) remained in the trial. Improvements on the Scale of
      Prodromal Symptoms and Scale to Assess Unawareness of Mental Disorder scores were
      statistically significant at end point. Although the Subjective Well-being Under
      Neuroleptics, Short version total scores improved significantly at 4 weeks,
      however, they did not change significantly from baseline at 8 weeks. CONCLUSIONS:
      This trial suggests that aripiprazole not only produces a clinical benefit in
      prodromal subjects but also results in a high adherence to medication with
      immediate improvements in insight and subjective well-being. Although further
      placebo-controlled studies are needed, aripiprazole might be a first-line
      treatment for individuals at imminent risk for psychosis.

PMID- 19745641
TI  - Expanded studies of the pharmacokinetics and clinical effects of multidose
      sublingual triazolam in healthy volunteers.
AB  - Previous work described the pharmacokinetics and clinical effects of multidose
      sublingual triazolam (Halcion; Pharmacia & Upjohn Co, Kalamazoo, Mich). This
      laboratory study evaluated the hypothesis that incremental dosing of triazolam
      produces dose-dependent central nervous system depression that is profound and
      long lasting. Forty-nine healthy adults between the ages of 21 and 39 years, not
      receiving dental treatment, were randomly assigned to placebo (n = 12) or 1 of 3
      triazolam groups (0.25-mg single dose, n = 12; 0.5 mg divided between 2 equal
      doses for 60 minutes, n = 12; or 0.75 mg divided among 3 doses for 90 minutes, n
      = 13). Plasma triazolam concentrations were determined. Bispectral index (BIS)
      and the Observer Assessment of Alertness/Sedation scale were used to assess
      sedation. Plasma triazolam concentrations increased with time in all subjects,
      with Tmax and Cmax both increasing dose dependently. Compared with placebo, all
      dosing paradigms produced dose-dependent BIS suppression and sedation. The single
      dose of 0.25 mg reached its peak BIS suppression at 90 (81 +/- 7) minutes and
      sedation at 120 (3.6 +/- 0.5) minutes and returned to baseline before 360
      minutes. In contrast, incremental dosing of 0.5 and 0.75 mg produced profound and
      long-lasting BIS suppression and sedation that did not plateau until either 180
      or 210 minutes as measured by the BIS index (67 +/- 14 and 60 +/- 16 at 0.5 and
      0.75 mg, respectively) and 150 minutes as measured by the Observer Assessment of
      Alertness/Sedation scale (3.2 +/- 1.0 and 2.7 +/- 0.4 at 0.5 and 0.75 mg,
      respectively). These data more fully characterize the effects of incremental
      dosing with sublingual triazolam and provide additional insight for discharge
      safety recommendations.

PMID- 19745642
TI  - Highway driving in the elderly the morning after bedtime use of hypnotics: a
      comparison between temazepam 20 mg, zopiclone 7.5 mg, and placebo.
AB  - A major problem related to hypnotic drug use is residual sedation the morning
      after bedtime administration. This constitutes a particular safety hazard for
      patients who have to drive a car the next morning. Information on the severity of
      residual effects is mainly derived from studies conducted with young healthy
      volunteers. However, most users of hypnotics are older people who may be more
      sensitive to drug effects. The aim of this study was to evaluate the residual
      effects the morning after evening doses of temazepam 20 mg and zopiclone 7.5 mg
      on driving performance in healthy elderly drivers. Eighteen healthy elderly
      drivers (10 females and 8 males; mean age, 64.3 years) participated in a double
      blind, 3-way crossover study. Treatments were single oral doses of temazepam 20
      mg, zopiclone 7.5 mg, and placebo administered at bedtime. Subjects performed a
      standardized highway driving test between 10 and 11 hours after hypnotic intake.
      Before and after the driving test, cognitive performance was assessed. Driving
      performance did not differ between temazepam and placebo but was significantly
      impaired after zopiclone 7.5 mg (P < 0.002). The results of the laboratory tests
      were in line with the effects on driving of both hypnotics. Temazepam 20 mg is
      unlikely to impair driving 10 hours or more after bedtime administration in
      healthy elderly aged 75 years or younger. Zopiclone 7.5 mg moderately impairs
      driving in the elderly at least until 11 hours after administration. The
      magnitude of impairing effects in the elderly was comparable with those found
      previously in younger volunteers.

PMID- 19745643
TI  - Comparing the stimulant effects of the H1-antagonist fexofenadine with 2
      psychostimulants, modafinil and methylphenidate.
AB  - BACKGROUND: Although antihistamines are known for their sedative adverse effects,
      fexofenadine was previously shown to have stimulating effects. These stimulant
      effects were rather mild in magnitude and were only demonstrated in tasks with a
      high workload. AIM: The present study was set up to compare the magnitude of the
      stimulant effect of fexofenadine with those of 2 psychostimulants, modafinil and
      methylphenidate. METHOD: Sixteen healthy volunteers (5 males and 11 females; mean
      age, 21.8 years) participated in a 4-way, placebo-controlled, crossover study.
      The effects of fexofenadine (360 mg), modafinil (200 mg), methylphenidate (20
      mg), and placebo were compared in a critical tracking, divided attention, motor
      impulsivity, and vigilance task. RESULTS: In this study, no significant stimulant
      effects of fexofenadine were found in any of the tasks. Modafinil only improved
      reaction time in the vigilance task, whereas methylphenidate improved performance
      in the divided attention and vigilance tasks. In addition, performance after
      methylphenidate treatment was also better than after fexofenadine in the divided
      attention and vigilance tasks. CONCLUSION: From the results, it can be concluded
      that the stimulating effects of methylphenidate are confirmed, whereas the
      stimulating effects of fexofenadine were not demonstrated in this study. It is
      evident that the stimulating effects of fexofenadine, which were apparent in
      previous studies, are not of the same magnitude as the effects of known
      psychostimulants such as methylphenidate.

PMID- 19745644
TI  - Effects of dextromethorphan/quinidine on auditory event-related potentials in
      multiple sclerosis patients with pseudobulbar affect.
AB  - The purpose of this study was to characterize the brain activity and associated
      cortical structures involved in pseudobulbar affect (PBA), a condition
      characterized by uncontrollable episodes of laughing and/or crying in patients
      with multiple sclerosis before and after treatment with
      dextromethorphan/quinidine (DM/Q). Behavioral responses and event-related
      potentials (ERPs) in response to subjectively significant and neutral verbal
      stimuli were recorded from 2 groups: 6 multiple sclerosis patients with PBA
      before (PBA-preTx) and after (PBA-DM/Q) treatment with DM/Q and 6 healthy control
      (HC) subjects. Statistical nonparametric mapping comparisons of ERP source
      current density distributions between groups were conducted for subjectively
      significant and neutral stimuli separately before and after treatment with DM/Q.
      Treatment with DM/Q had a normalizing effect on the behavioral responses of PBA
      patients. Event-related potential waveform comparisons of PBA-preTx and PBA-DM/Q
      with HC, for both neutral and subjectively significant stimuli, revealed effects
      on early ERP components. Comparisons between PBA-preTx and HC, in response to
      subjectively significant stimuli, revealed both early and late effects. Source
      analysis comparisons between PBA-preTx and PBA-DM/Q indicated distinct
      activations in areas involved in emotional processing and high-level and
      associative visual processing in response to neutral stimuli and in areas
      involved in emotional, somatosensory, primary, and premotor processing in
      response to subjectively significant stimuli. In most cases, stimuli evoked
      higher current density in PBA-DM/Q compared with the other groups. In conclusion,
      differences in brain activity were observed before and after medication. Also,
      DM/Q administration resulted in normalization of behavioral and
      electrophysiological measures.

PMID- 19745645
TI  - Atomoxetine and cerebrovascular outcomes in adults.
AB  - OBJECTIVE: The aim of this study was to estimate the association between
      atomoxetine and cerebrovascular accident (CVA) and transient ischemic attack
      (TIA) in adults. METHODS: This cohort study conducted within a health insurance
      database included 21,606 atomoxetine initiators matched to 21,606 stimulant
      attention-deficit/hyperactivity disorder (ADHD) medication initiators on the
      basis of propensity scores and a sample from the source population (N = 42,993).
      Outcomes were confirmed through a medical record review or a National Death Index
      search. Poisson regression was used to estimate the rate ratio and 95% confidence
      interval (CI) of CVA or TIA according to the treatment. Cox regression was used
      to estimate the hazards ratio (HR) and 95% CI for comparisons across cohorts.
      RESULTS: Forty-four CVAs and 21 TIAs occurred during a mean follow-up of 1.5
      years. The rate ratio of the current atomoxetine compared with the current
      stimulant ADHD medication was 1.38 for CVA (95% CI, 0.42-4.54) and 0.31 for TIA
      (95% CI, 0.04-2.63). Results for atomoxetine compared with the stimulant ADHD
      medication according to initial cohort assignment were consistent, with no
      increased risk for CVA or TIA. An increased risk of TIA was observed between
      initiation of an ADHD medication compared with the general population (HR, 3.44;
      95% CI, 1.13-10.60); however, a similar pattern was not observed for CVA (HR,
      0.71; 95% CI, 0.34-1.47). CONCLUSIONS: These results do not support an increased
      risk of CV events with atomoxetine compared with the stimulant ADHD medication.
      Users of ADHD medications may be at an increased risk of TIA compared with the
      general population.

PMID- 19745646
TI  - Personality trait dimensions and the pharmacological treatment of borderline
      personality disorder.
AB  - The number of well-designed placebo-controlled studies on pharmacological
      treatment of borderline personality disorder has been small. We present a
      breakdown of results of placebo-controlled pharmacological studies, sorting
      target symptoms into the trait dimensions of affective instability, anxiety
      inhibition, cognitive-perceptual disturbances, and impulsivity-aggression. Twenty
      randomized placebo-controlled pharmacological trials studying typical and
      atypical antipsychotics, selective serotonin reuptake and monoamine oxidase
      inhibitors, tricyclic antidepressants, mood stabilizers, and benzodiazepines were
      included. A relative measure of the weight of an outcome was determined by (1)
      dividing the number of positive comparisons for a drug class by the total number
      of comparisons of all drugs of all classes for each dimension and (2) dividing
      the number of positive comparisons for a drug class by the total number of
      comparisons for that particular drug class for that trait dimension.
      Antipsychotics (neuroleptics and atypicals) had the most evidence for each of the
      traits with both methods. Our results are compared with the results of 2 meta
      analyses, 1 guideline set, and 1 other systematic review. We found little
      concordance across these studies. We propose a consortium to discuss guidelines
      for future studies, including agreement as to what should be measured to
      determine the outcome and adoption of standardized instruments to measure that
      outcome.

PMID- 19745647
TI  - Impact of early pharmacological treatment on cognitive and behavioral outcome
      after traumatic brain injury in adults: a meta-analysis.
AB  - Early pharmacological treatment has the potential to reduce some of the disabling
      cognitive and behavioral problems that result from traumatic brain injury (TBI).
      Although a large number of treatments have been developed, clinical research has
      yielded inconsistent findings with respect to the effectiveness of these
      pharmacological treatments on cognitive and behavioral outcomes. Furthermore,
      their relative efficacy has not been evaluated, thereby hindering advances in the
      treatment of TBI. A meta-analysis of research that examined the impact of
      pharmacological treatments on cognitive and behavioral outcomes in the early
      stages after TBI between January 1980 and May 2008 was therefore undertaken. The
      PubMed and PsycINFO databases were searched using 35 terms. All articles were
      screened using detailed inclusion criteria. Weighted Cohen's d effect sizes,
      percent overlap statistics, and fail-safe N statistics were calculated for each
      pharmacological agent. Studies that used different experimental designs were
      examined separately. Eleven pharmacological treatments were investigated by 22
      clinical studies, comprising 6472 TBI patients in the treatment groups and 6460
      TBI controls. One dopamine agonist (amantadine) and 1 bradykinin antagonist (CP
      0127 [Bradycor]) produced marked treatment benefits (d > or = 0.8) for a single
      measure of arousal (Glasgow Coma Scale). Notably, drug dosage and the measure
      chosen to assess outcome influenced the probability of finding a treatment
      benefit.

PMID- 19745648
TI  - Randomized, double-blind, placebo-controlled trial of Cimicifuga racemosa (black
      cohosh) in women with anxiety disorder due to menopause.
AB  - OBJECTIVE: We conducted a randomized, double-blind, placebo-controlled, parallel
      group trial of the efficacy and tolerability of Cimicifuga racemosa (black
      cohosh) extract for the treatment of anxiety disorder due to menopause. We
      hypothesized that black cohosh would be superior to placebo in reducing anxiety
      symptoms of menopause, with a comparable tolerability profile to placebo.
      MATERIALS AND METHODS: Subjects were randomized to therapy with either
      pharmaceutical-grade black cohosh extract (n = 15) or placebo (n = 13) for up to
      12 weeks. The primary outcome measure was changed over time in total Hamilton
      Anxiety Rating Scale (HAM-A) scores. Secondary outcomes included a change in
      scores on the Beck Anxiety Inventory, Green Climacteric Scale (GCS), and
      Psychological General Well-Being Index (PGWBI) and the proportion of patients
      with a change of 50% or higher in baseline HAM-A scores. RESULTS: There was
      neither a significant group difference in change over time in total HAM-A scores
      (P = 0.294) nor a group difference in the proportion of subjects with a reduction
      of 50% or higher in baseline HAM-A scores at study end point (P = 0.79). There
      was a significantly greater reduction in the total GCS scores during placebo (vs
      black cohosh; P = 0.035) but no group difference in change over time in the GCS
      subscale scores or in the PGWBI (P = 0.140). One subject (3.6%) taking black
      cohosh discontinued treatment because of adverse events. CONCLUSIONS: We found no
      statistically significant anxiolytic effect of black cohosh (vs placebo).
      However, small sample size, choice of black cohosh preparation, and dosage used
      may have been limiting factors producing negative results.

PMID- 19745649
TI  - Randomized controlled trial of atomoxetine for cognitive dysfunction in early
      Huntington disease.
AB  - BACKGROUND: Cognitive symptoms are associated with functional disability in
      Huntington disease; yet, few controlled trials have examined cognitive treatments
      that could improve patient independence and quality of life. Atomoxetine is a
      norepinephrine reuptake inhibitor approved for treatment of attention
      deficit/hyperactivity disorder. METHODS: Twenty participants with mild Huntington
      disease who complained of inattention were randomized to receive atomoxetine (80
      mg/d) or placebo in a 10-week double-blind crossover study. Primary outcome
      measures were self-reported attention and attention and executive
      neuropsychological composite scores. Secondary outcomes were psychiatric and
      motor symptom scores. RESULTS: The rate of reported adverse effects while on
      atomoxetine was 56% (vs 35% on placebo), which most commonly included dry mouth
      (39%), loss of appetite (22%), insomnia (22%), and dizziness (17%). There were no
      serious adverse events related to atomoxetine. There were statistically
      significant, although mild, increases in heart rate and diastolic blood pressure
      on atomoxetine, consistent with other studies and not requiring medical referral.
      There were no significant improvements while on atomoxetine compared with placebo
      on primary outcomes. However, there was evidence of significant placebo effects
      on self-reported attention and psychiatric functions. There were no group
      differences on the Unified Huntington's Disease Rating total motor score.
      CONCLUSIONS: Atomoxetine demonstrated no advantages over placebo for primary or
      secondary outcomes. Although atomoxetine was not effective at improving attention
      at this dose, its safety and tolerability were similar to other studies.

PMID- 19745650
TI  - Open-label pilot study of modafinil for methamphetamine dependence.
AB  - Methamphetamine has become a major public health issue globally, particularly in
      the United States. Despite this, no effective pharmacotherapy for methamphetamine
      abuse has been developed to date. This 6-week, open-label pilot clinical trial
      examined the safety and tolerability of modafinil up to 400 mg/d in 8
      methamphetamine-dependent individuals. Subjects were inducted onto modafinil at
      400 mg/d for more than 3 days and remained on 400 mg/d for 4.5 weeks.
      Participants received weekly blister packs and underwent weekly individual
      cognitive behavioral therapy. Adjunctive contingency management procedures were
      used to enhance retention. Vital signs and supervised urine samples were obtained
      thrice weekly, and self-reported drug use and Hamilton anxiety and depression
      ratings were completed once weekly. Eight subjects (50% female, 100% white, aged
      35-52 years) were enrolled. Four completed the 6-week study, 3 completed a
      portion, and 1 withdrew consent before completing intake. Results showed that
      systolic blood pressure (t = 1.09, P = 0.28), diastolic blood pressure, (t =
      1.18, P = 0.24), and heart rate (t = 1.55, P = 0.13) did not change over time.
      Scores on the modafinil side effects checklist (t = -2.63, P = 0.01), Hamilton
      anxiety scale (t = -2.50, P = 0.018), and Hamilton depression scale (t = -3.25, P
      = 0.003) all decreased over time. The proportion of urine positive for
      amphetamines did not change over time (t = -0.52, P = 0.61), whereas self
      reported methamphetamine use did (t = -2.86, P < 0.005). These results suggest
      that modafinil at 400 mg/d is safe and tolerable for methamphetamine-dependent
      individuals.

PMID- 19745651
TI  - Overnight versus progressive conversion of multiple daily-dose divalproex to once
      daily divalproex extended release: which strategy is better tolerated by adults
      with intellectual disabilities?
AB  - Divalproex (DVP) delayed release and DVP extended release (DVP ER) are approved
      by the Food and Drug Administration for bipolar disorder, epilepsy, and migraine
      prophylaxis. Divalproex ER is given once daily, improving compliance and reducing
      adverse events. Overnight switch to DVP ER is advised in the package insert but
      could produce more adverse events in this susceptible population. In this pilot
      study, we compared tolerability of overnight versus gradual switching to DVP ER
      in 16 adults with intellectual and developmental disabilities receiving DVP, in 9
      for epilepsy and in all 16 for comorbid bipolar disorder. The study design was
      open with parallel groups. Sixteen subjects with intellectual and developmental
      disabilities were randomized to overnight or gradual conversion for 4 to 6 days.
      A blinded rater completed the Multidimensional Observation Scale for Elderly
      Subjects on days +1, +4, and +8 after the switch began. We found no major
      differences between the 2 groups at each time point. Neither group of subjects,
      except for 1 subject in the overnight group, manifested sedation, seizures,
      worsening of tremor, or gastrointestinal adverse events. One subject in the
      overnight group manifested acute diarrhea and vomiting, followed by a very brief
      tonic leg seizure 6 days later. Larger studies are warranted.

PMID- 19745652
TI  - Independent effect of paliperidone extended release on social functioning beyond
      its effect on positive and negative symptoms of schizophrenia: a mediation
      analysis.

PMID- 19745653
TI  - Atypical neuroleptic malignant syndrome with quetiapine: a case report and review
      of the literature.

PMID- 19745654
TI  - Oral urea treatment for polydipsia-hyponatremia syndrome in patients with
      schizophrenia.

PMID- 19745655
TI  - Clozapine monotherapy for 66 months in treatment resistant bipolar disorder: a
      case report.

PMID- 19745656
TI  - Waxing-and-waning catatonia after intermittent exposure to aripiprazole in a case
      of autism and bipolar disorder.

PMID- 19745657
TI  - Asymptomatic hyperamylasemia and hyperlipasemia associated with aripiprazole.

PMID- 19745658
TI  - A case of aripiprazole-associated paroxysmal supraventricular tachycardia.

PMID- 19745659
TI  - Possible lamotrigine-induced mania in a child with autism spectrum disorder and
      epilepsy.

PMID- 19745660
TI  - Valproic acid toxicity associated with low dose of aspirin and low total valproic
      acid levels: a case report.

PMID- 19745661
TI  - Combination therapy of acetylcholinesterase inhibitor and vitamin E in Alzheimer
      disease.

PMID- 19745662
TI  - Treatment of unipolar psychotic depression: an open study of lithium addition in
      refractory psychotic depression.

PMID- 19745664
TI  - Myopia affects retinal nerve fiber layer measurements as determined by optical
      coherence tomography.
AB  - PURPOSE: To determine whether increasing myopia is associated with thinner
      peripapillary retinal nerve fiber layer (RNFL) when measured by Stratus optical
      coherence tomography (OCT). DESIGN: Observational cross-sectional study. METHODS:
      Normal subjects with myopia underwent refractometry, axial length measurement
      (IOL Master), optic nerve examination, and OCT (12 fast RNFL scans/eye). The more
      myopic eye was chosen as the study eye. Correlation coefficients were calculated
      for demographic and optic disk characteristics, and degree of myopia. RESULTS:
      Mean age (n=27) was 34+/-8 years (range: 23 to 54). Mean cup-to-disk ratio was
      0.38 with 41% large and 59% medium disk size. Eight subjects had peripapillary
      atrophy and 6 had disk tilt. Mean spherical equivalent was -5.40 D (range: -1.25
      to -11.25), with mean axial length of 25.65 mm (range: 22.63 to 27.92). No
      significant associations were found between RNFL thickness and age (P=0.20), sex,
      disk size, cup-to-disk ratio, tilt, or peripapillary atrophy. RNFL thickness
      decreased with higher axial length (overall R=-0.70, P<0.001, superior R=-0.60,
      P=0.001, and inferior R=-0.60, P=0.001), and higher spherical equivalent (overall
      R=-0.52, P=0.005, superior R=-0.41, P=0.03, and inferior R=-0.45, P=0.02).
      Overall RNFL thickness decreased 7 mum/1 mm of axial length, and 3 mum/1 D
      sphere. CONCLUSIONS: Moderately myopic subjects tend to have thin peripapillary
      RNFL, mainly at the superior and inferior poles, as measured by Stratus OCT. This
      phenomenon should be considered when interpreting a glaucoma suspect's Stratus
      OCT measurements compared with the normative database.

PMID- 19745665
TI  - Potential of the pentacam in screening for primary angle closure and primary
      angle closure suspect.
AB  - PURPOSE: To compare the Pentacam to ultrasound biomicroscopy (UBM) or gonioscopy
      in detecting eyes with primary angle closure (PAC), including PAC suspect and PAC
      glaucoma. PATIENTS AND METHODS: In 72 eyes of 39 Japanese with various anterior
      chamber angle (ACA) widths, the ACA, anterior chamber depth (ACD), and anterior
      chamber volume (ACV) were measured using the Pentacam, and the ACA was measured
      by UBM (ACAUBM). Correlations among these parameters and Shaffer's grade based on
      gonioscopy in the corresponding quadrant were studied. The efficacy of the
      Pentacam in screening for PAC and PAC suspect was then analyzed by using
      receiving operator characteristic (ROC) curves and partition analysis. RESULTS:
      Shaffer's classification (grade 0 to 4) significantly correlated with each of the
      measurements using both screening devices (P<0.001), and most strongly correlated
      with ACAUBM. ACAUBM was also significantly correlated with each Pentacam
      parameter in all subjected eyes with angle widths of grades 0 to 4 (P<0.001), but
      not grade 2 or less (P>0.05). In screening eyes with PAC and PAC suspect with the
      Pentacam, the area under the ROC curve was largest (0.943) when ACV was used as
      the reference, and partition analysis showed that those eyes were most
      effectively partitioned with an ACD of 2.58 mm using the Pentacam, resulting in
      100% sensitivity and 87.1% specificity. CONCLUSIONS: The Pentacam has potential
      for safe, noncontact screening of eyes with PAC and PAC suspect, except for those
      with plateau iris configurations, based on measurements of the ACV and ACD, but
      not the ACA.

PMID- 19745666
TI  - Follow-up of primary angle closure suspects after laser peripheral iridotomy
      using ultrasound biomicroscopy and A-scan biometry for a period of 2 years.
AB  - AIM: To determine the morphologic changes in the anterior segment of primary
      angle closure suspects (PACS) who underwent laser peripheral iridotomy (LPI) for
      a period of 2 years. METHODS: PACS (n=82 eyes) of Asian Indian origin who
      attended the Glaucoma clinic of tertiary eye hospital underwent A-scan biometry
      and ultrasound biomicroscopy. Anterior chamber depth, anterior chamber angle
      (ACA), axial length, lens thickness, relative lens position, central corneal
      thickness, angle opening distance 500, trabecular-ciliary process distance, iris
      ciliary process distance, and iris thickness were measured before LPI and after
      LPI at 1 week, 6 months, 1 year, 1.5 years, and 2 years. Variation in the
      parameters measured over a period of 2 years was analyzed. RESULTS: Fifteen eyes
      out of 52 eyes developed into primary angle closure (PAC) with synechial changes.
      Univariate analysis for the predictive factors of PAC showed no significant
      association for age, sex, narrow angle, ultrasound biomicroscopy parameters, and
      vertical cup-disc ratio. When analyzed as continuous variables, decreasing ACA
      was significant risk factor (95% confidence interval: 0.703, 0.989, P=0.037).
      Iris-ciliary process distance, ACA, lens thickness, and angle opening distance
      500 were the parameters that varied significantly (P<0.05) between "before LPI
      group" and "after LPI groups." None of the subjects developed increased
      intraocular pressure after laser iridotomy. CONCLUSIONS: In this hospital-based
      study on the course of PACS subjects after LPI, as many as 28% progressed to PAC.
      Decreasing ACA was the predictive factor for the progression of PACS to PAC.
      There was no increase in intraocular pressure, history, or symptoms of acute
      attack of glaucoma among the study subjects after LPI.

PMID- 19745667
TI  - Comparison of retinal nerve fiber layer thickness values using Stratus Optical
      Coherence Tomography and Heidelberg Retina Tomograph-III.
AB  - PURPOSE: To evaluate the usefulness of retinal nerve fiber layer (RNFL) thickness
      measurements using the Heidelberg Retina Tomograph-III (HRT-III) in normal,
      ocular hypertensive, and glaucomatous eyes and compare the thickness measurements
      using HRT-III and Stratus Optical Coherence Tomography-3 (OCT-3). METHODS: Sixty
      nine normal eyes, 60 eyes ocular hypertensive, and 111 glaucomatous were
      included. All participants underwent visual field, HRT-III, and OCT-3
      examinations on the same day. Patients were classified into 3 groups according to
      intraocular pressure and visual field damage. The sensitivity/specificity of RNFL
      thickness measurements and RNFL thickness classifications using HRT-III and OCT-3
      were calculated. The sensitivity/specificity of the height variation contour
      (HVC) from the HRT-III were calculated. The receiver operating characteristic
      curves (ROC) and areas under the ROC were plotted. Agreement was calculated using
      Bland-Altman method and the kappa coefficient. RESULTS: The RNFL thickness
      sensitivity/specificity were 32.4%/87%, for the HRT-III and 72.97%/81.15% for the
      OCT-3 in relation to the glaucoma diagnosis (least specific criteria). The RNFL
      thickness sensitivities/specificities were lower in early glaucoma. The areas
      under the ROC for RNFL measurements were 0.72 using HRT-III, 0.86 with OCT-3
      (P=0.001), and 0.54 for the HVC. The RNFL classification kappa coefficient was
      0.36. Bland-Altman analysis confirmed that the RNFL measurements were not
      interchangeable. CONCLUSIONS: The sensitivity of RNFL damage detection using HRT
      III was lower compared with OCT-3, especially in early glaucoma. RNFL thickness
      agreement between HRT-III and OCT-3 was only fair. HVC was not useful for
      glaucoma detection.

PMID- 19745668
TI  - Physiologic significance of steady-state pattern electroretinogram losses in
      glaucoma: clues from simulation of abnormalities in normal subjects.
AB  - PURPOSE: To better understand pathophysiologic mechanisms underlying pattern
      electroretinogram (PERG) losses in glaucoma by simulating either retinal ganglion
      cell (RGC) dysfunction or RGC loss in normal subjects. MATERIALS AND METHODS: The
      steady-state PERG has been recorded in 10 normal subjects (mean age: 31+/-8 y)
      according to the PERGLA paradigm by means of skin electrodes in response to
      horizontal gratings (1.7 cycles/degree, 99% contrast, 40 cd/m mean luminance,
      circular field size 25 degree diameter) alternating 16.28 times/seconds.
      Simulated RGC dysfunction has been obtained by reducing either contrast and mean
      luminance or blurring the visual stimulus. Simulated RGC loss has been obtained
      by reducing stimulus area. Outcome measures were PERG amplitude and phase
      obtained by discrete Fourier transform of PERG waveforms. RESULTS: Progressive
      PERG amplitude reductions spanning the entire dynamic range of PERG response
      could be obtained by progressively reducing stimulus contrast and luminance,
      blurring the stimulus, and reducing stimulus area. The same variations in
      stimulus conditions caused phase changes of disparate sign and magnitude. Phase
      advanced (latency shortened) by reducing stimulus contrast or blurring the
      stimulus; phase lagged (latency increased) by reducing stimulus luminance; phase
      remained constant by reducing stimulus area. CONCLUSIONS: PERG amplitude and
      phase are essentially uncoupled, implying that these measures reflect distinct
      aspects of RGC activity. On the basis of our results and known PERG physiology,
      we propose a model in which both RGC dendrites and RGC axons contribute to the
      PERG signal. PERG delays may represent an indication of synaptic dysfunction that
      is potentially reversible.

PMID- 19745669
TI  - The association between self-reported glaucoma and ginkgo biloba use.
AB  - PURPOSE: To assess the association between Ginkgo biloba extract (GBE) use and
      glaucoma. METHODS: Self-reported data on the past 12 months of GBE use and the
      presence of glaucoma were obtained from the 2002 National Health Interview
      Survey, a nationally-representative population-based sample. Crude and adjusted
      associations between GBE use and glaucoma were estimated. RESULTS: Those who
      reported having glaucoma were 26% less likely to report GBE use; however, this
      was not statistically significant. After adjustment for potentially confounding
      demographic and medical characteristics, there was no difference in GBE use among
      those who did and did not report having glaucoma. CONCLUSIONS: The results of
      this study fail to support a significant relationship between GBE use over the
      past 12 months and having glaucoma, though this finding requires replication in a
      prospective study. Moreover, whether GBE is efficacious in treating glaucoma
      patients remains an issue for future research.

PMID- 19745670
TI  - "Bleb window"-pexy for the management of symptomatic, oversized blebs.
AB  - PURPOSE: To describe a simple method and outcomes of remodeling dysesthetic,
      oversized filtering blebs. PATIENTS AND METHODS: Retrospective chart review of
      the initial consecutive patients who had undergone "bleb window"-pexy (BWP) over
      a 1-year period. Patients with symptomatic, oversized, and dysmorphic blebs that
      did not show signs of spontaneous resolution were candidates for the technique,
      regardless of the intraocular pressure. Under topical anesthesia, a conjunctival
      window was created in the filtering bleb at the palpebral fissure (nasal or
      temporal) using Westcott scissors. The cut edges of conjunctiva and Tenon capsule
      were then glued to the underlying bare sclera using autologous fibrin tissue
      glue. In the case of extended (360 degrees) blebs (2 patients), 2 conjunctival
      windows were performed (nasal and temporal). Main outcome included symptomatic
      relief, restoration of bleb architecture, and preservation of filtration.
      RESULTS: Six eyes from 6 patients underwent BWP. The mean follow-up period was
      6.6+/-1.7 months (3.5 to 8.3 mo). All patients documented a rapid symptomatic
      relief within the first postoperative day. All had successful reduction in bleb
      size and adequate filtration without further antiglaucoma medications or surgery.
      Best corrected visual acuity improved 2 Snellen lines in 1 eye. Lens status
      remained unchanged in all cases. No complications or recurrences were noted.
      CONCLUSIONS: Early results showed that BWP is safe, easy, and minimally invasive
      technique for the rapid relief of dysesthesia symptoms from dysmorphic filtering
      blebs. A larger sample size with longer follow-up is necessary to confirm the
      clinical utility.

PMID- 19745671
TI  - Cataract and glaucoma case detection for Vision 2020 programs in Africa: an
      evaluation of 6 possible screening tests.
AB  - PURPOSE: To determine if there is a screening test or a combination of screening
      tests that may be suitable for cataract and glaucoma case detection in Vision
      2020 programs in Africa. METHODS: Design-Screening methods validation study.
      Setting-Groote Schuur Hospital, Cape Town, South Africa. Subjects-African
      patients aged 40 years and older with known cataract or with known glaucoma, and
      accompanying relatives aged 40 years and older with no known eye pathology.
      Outcome measures-Sensitivity, specificity, positive and negative likelihood
      ratios, and accuracy of 6 screening tests, used alone and in various
      combinations. RESULTS: Testing the pinhole visual acuity using a cut point of
      6/18 in 1 or both eyes has a sensitivity and specificity greater than 90%, a
      positive likelihood ratio greater than 10.0, a negative likelihood ratio less
      than 0.1, and an accuracy greater than 90% for case detection of cataract or
      glaucoma. Examination of the optic disk with a lens free direct ophthalmoscope
      using a cut point of 0.7 for the vertical cup:disk ratio combined with testing
      for an afferent pupil defect has similar values for case detection of glaucoma.
      CONCLUSIONS: These tests may be suitable for use in Vision 2020 programs in
      Africa.

PMID- 19745672
TI  - Selective laser trabeculoplasty for primary angle closure with persistently
      elevated intraocular pressure after iridotomy.
AB  - PURPOSE: To determine whether selective laser trabeculoplasty (SLT) can lower
      intraocular pressure (IOP) in eyes with chronic primary angle closure, elevated
      IOP, and a patent iridotomy. PATIENTS AND METHODS: Patients with chronic angle
      closure who had underwent iridotomy, had an IOP greater than 21 mm Hg and a
      gonioscopically visible pigmented trabecular meshwork for at least 90 degrees
      were enrolled. SLT was applied to open angle segments. Duration of follow-up was
      6 months. RESULTS: Sixty eyes of 60 patients were enrolled. The mean baseline IOP
      was 24.6+/-2.5 mm Hg. At 6 months, IOP reduction of > or =3 mm Hg or 4 mm Hg was
      measured in 82% and 72% of eyes, respectively, and IOP reduction of > or =20% or
      30% was measured in 54% and 24% of eyes, respectively. When only eyes that were
      treated with the same number or fewer medications were considered, these IOP
      reductions were measured in 67%, 58%, 43%, and 15%, respectively. During the
      study period 1 eye (1.7%) required trabeculectomy owing to IOP elevation shortly
      after the SLT. There were no other significant complications attributable to SLT.
      CONCLUSIONS: SLT seems to be a safe and effective method of reducing IOP in many
      eyes with primary angle closure and a patent iridotomy in which there is a
      sufficient extent of visible trabecular meshwork.

PMID- 19745673
TI  - Recurrent angle-closure glaucoma.

PMID- 19745685
TI  - Comprehensive outpatient health assessment: a case-finding tool in 500
      consecutive asymptomatic individuals.
AB  - This study appraises the case-finding efficiency of a single-day outpatient
      program of a broad-based clinical evaluation and laboratory studies in
      asymptomatic adults. The same protocol, varied only according to age and sex, was
      used for 500 individuals encountered consecutively over 15 months, and an
      unanticipated new diagnosis or important clinical or laboratory finding was
      established for one-third of them. The diagnoses varied widely, consistent with
      the breadth of the observations, and most led to specific recommendations for
      care. These findings confirm the case-finding efficacy of comprehensive clinical
      assessments supported by basic laboratory studies and counter the notion that
      specific tests and/or portions of the review of systems and physical examination
      can be eliminated in establishing a reliable medical database for asymptomatic
      adults. In addition, such comprehensive data provide essential reference material
      for later comparisons.

PMID- 19745684
TI  - Infectious diseases consultation lowers mortality from Staphylococcus aureus
      bacteremia.
AB  - Staphylococcus aureus bacteremia (SAB) is a lethal and increasingly common
      infection in hospitalized patients. We assessed the impact of infectious diseases
      consultation (IDC) on clinical management and hospital mortality of SAB in 240
      hospitalized patients in a retrospective cohort study. Patients who received IDC
      were older than those who did not (57.9 vs. 51.7 yr; p = 0.05), and were more
      likely to have a health care-associated infection (63% vs. 45%; p < 0.01). In
      patients who received IDC, there was a higher prevalence of severe complications
      of SAB such as central nervous system involvement (5% vs. 0%, p = 0.01),
      endocarditis (20% vs. 2%; p < 0.01), or osteomyelitis (15.6% vs. 3.4%; p < 0.01).
      Patients who received IDC had closer blood culture follow-up and better
      antibiotic selection, and were more likely to have pus or prosthetic material
      removed. Hospital mortality from SAB was lower in patients who received IDC than
      in those who did not (13.9% vs. 23.7%; p = 0.05). In multivariate survival
      analysis, IDC was associated with substantially lower hazard of hospital
      mortality during SAB (hazard 0.46; p = 0.03). This mortality benefit accrued
      predominantly in patients with methicillin-resistant SAB (hazard 0.3; p < 0.01),
      and in patients who did not require ICU admission (hazard 0.15; p = 0.01). In
      conclusion, IDC is associated with reduced mortality in patients with
      staphylococcal bacteremia.

PMID- 19745686
TI  - Management of Bacillus bacteremia: the need for catheter removal.
AB  - Bacillus species are biofilm-forming organisms that are associated with Bacillus
      catheter-related bloodstream infections (CRBSIs). The optimal treatment of
      Bacillus CRBSIs is not known. Therefore, in the current study, we determined the
      role of long-term central venous catheter (CVC) removal and treatment with
      vancomycin compared with other agents in Bacillus CRBSIs by retrospectively
      reviewing the medical records of cancer patients with Bacillus bacteremia who had
      been treated at our institution from December 1990 to March 2008. True bacteremia
      was defined as a positive blood culture (>15 colony-forming units/mL) with signs
      and symptoms of infection (such as fever and chills). Bacillus CRBSI was defined
      in accordance with the Infectious Diseases Society of America guidelines as
      probable or definite. There were 94 Bacillus bacteremia episodes, 93 of which
      (99%) were Bacillus CRBSIs (28% definite and 71% probable). Neutropenia during
      bacteremia occurred in 29%. Almost all bacteremia patients (99%) had been treated
      with antibiotics; 63% had received vancomycin. Sepsis with hypotension occurred
      in 6%, and endocarditis in 1%. Bacillus isolates were susceptible to linezolid
      (100%), vancomycin (98%), tetracycline (77%), and rifampin (67%). All 4
      recurrences occurred in patients in whom the CVC had not been removed (12%),
      whereas no recurrences occurred in patients whose CVC had been removed (p =
      0.028). Patient outcome, in terms of fever and hospitalization duration after the
      infection, was similar in patients who had received < or =10 days of systemic
      antibiotics compared with patients who had received >10 days. In conclusion,
      catheter retention in patients with Bacillus CRBSIs is associated with a
      significantly higher recurrence rate. If the CVC is retained, treatment with non
      vancomycin antibiotics is associated with significantly shorter hospitalization
      duration after the infection, which may be because glycopeptide antibiotics have
      poor activity against bacilli embedded in biofilm.

PMID- 19745687
TI  - Hematologic manifestations and predictors of lymphoma development in primary
      Sjogren syndrome: clinical and pathophysiologic aspects.
AB  - The diverse hematologic manifestations of primary Sjogren syndrome (pSS) have not
      been systematically investigated, and their prognostic relevance remains unclear.
      We conducted a retrospective study of 536 consecutive patients followed in our
      institution to assess the prevalence of hematologic abnormalities and their
      associations with various disease manifestations in pSS. We also aimed to
      identify risk factors for the development of non-Hodgkin lymphoma (NHL) overall
      and by subtype. Anemia of chronic disease and hypergammaglobulinemia were the
      most prevalent hematologic manifestations encountered at diagnosis and during the
      course of pSS. Univariate analysis between cytopenias and glandular
      manifestations revealed a statistically significant correlation between
      lymphocytopenia and parotid gland enlargement (p = 0.002), as well as between
      neutropenia and xerostomia (p = 0.019). Anemia, lymphocytopenia,
      thrombocytopenia, hypergammaglobulinemia, the presence of monoclonal serum
      proteins, and cryoglobulinemia correlated significantly with the presence of
      extraglandular symptoms such as palpable purpura, lymphadenopathy, and
      splenomegaly. Lymphoma was diagnosed in 7.5% (95% confidence interval [CI], 5.4%
      10%) of patients. Marginal zone B-cell lymphomas (MZBCLs) were the predominant
      histologic type (65%; 95% CI, 48.3%-79.4%), while diffuse large B-cell lymphomas
      (DLBCLs) accounted for 17.5% (95% CI, 7.3%-32.8%) of all cases. The development
      of NHL in patients with pSS could be predicted by the presence of simple clinical
      and laboratory factors at diagnosis: neutropenia (p = 0.041), cryoglobulinemia (p
      = 0.008), splenomegaly (p = 0.006), lymphadenopathy (p = 0.021), and low C4
      levels (p = 0.009). Patients carrying any of these factors had a more than 5-fold
      increased risk of NHL compared to patients with no risk factors at all. The above
      set of disease characteristics could predict subsequent development of MZBCL; the
      presence of lymphocytopenia (p = 0.044) at diagnosis served as a risk factor for
      the development of a non-MZBCL, most commonly DLBCL. Anemia of chronic disease
      and hypergammaglobulinemia are common hematologic manifestations at diagnosis and
      during the course of pSS. Neutropenia and cryoglobulinemia at diagnosis are
      significantly associated with an increased risk of lymphoma development.

PMID- 19745688
TI  - Resurgence of Pseudomonas endocarditis in Detroit, 2006-2008.
AB  - A resurgence of endocarditis due to Pseudomonas aeruginosa was seen in 10
      injection drug users (IDUs) in Detroit between 2006 and 2008 (6 men, 4 women;
      mean age, 48.1 yr). All patients tested negative for the human immunodeficiency
      virus (HIV). Five patients had left-sided endocarditis of the mitral valve and/or
      the aortic valve; 3 of 5 patients had prosthetic valve endocarditis. Four of 10
      patients had right-sided endocarditis of the tricuspid valve alone. One patient
      had bilateral involvement of the aortic and tricuspid valves. Nine patients had
      Pseudomonas endocarditis (PsE); 1 patient had mixed endocarditis with P.
      aeruginosa and Candida parapsilosis. Seven of 10 patients were treated with a
      combination of intravenous cefepime, 4-6 g/d, plus high-dose tobramycin (HDT) for
      at least 6 weeks. Tobramycin, 8 mg/kg per day, was given as a single daily dose
      intravenously, aiming for peak serum levels of 18-22 microg/mL and trough levels
      of <1 microg/mL. The patient with mixed endocarditis was also treated with
      fluconazole. Two patients initially treated with other antipseudomonal regimens,
      including cefepime alone and piperacillin/tazobactam plus tobramycin, failed
      treatment and were switched to cefepime and HDT. A third patient was switched to
      cefepime and ciprofloxacin because of nephrotoxicity. Two patients developed
      nephrotoxicity to tobramycin; 1 patient developed ototoxicity. The overall
      medical cure rate for both left-sided and right-sided disease was 80% (4/5). All
      5 patients who required surgery survived (5/5; 100%). Overall outcome was 90%
      (9/10). Indications for valve replacement were recurrent Pseudomonas bacteremia
      (n = 3), recurrent bacteremia and congestive heart failure (n = 1), and
      persistent bacteremia and fungemia (n = 1). Tricuspid valvulectomy with valve
      replacement was successful in 2 patients and in a third patient who had
      successful replacement of both the tricuspid and the aortic valve for recurrent
      bacteremia and congestive heart failure. Two patients with pure left-sided
      prosthetic valve endocarditis underwent successful repeat valve replacements.
      Although this is a small series, the overall mortality rate (1/10; 10%) was low.
      The patient who did not survive had left-sided involvement of the aortic valve
      and could not undergo surgery because of a large embolic cerebral infarct. The
      mortality rate of left-sided disease in the current series was 16.7% (1/6
      including the patient with tricuspid and aortic valve PsE) compared to 60% in a
      series of 15 patients reported in 1990.Our current antimicrobial regimen for PsE
      consists of a combination of cefepime, 6 g/d, in 3 divided doses, plus HDT, 8
      mg/kg per day, given as a single daily dose for 6 weeks. For cefepime-resistant
      Pseudomonas, imipenem, 4-6 g/d, or meropenem, 6 g/d, plus HDT has been
      successful. For right-sided disease refractory to medical therapy, surgical
      intervention is recommended if Pseudomonas bacteremia persists for 2 weeks on
      appropriate antimicrobial therapy or if bacteremia recurs after a 6-week course
      of treatment. Tricuspid repair/reconstruction or valvulectomy with valve
      replacement plus combined antipseudomonal regimen may be the optimal therapy for
      refractory right-sided endocarditis. This approach not only may prevent the
      development of severe and permanent impairment of right ventricular function,
      which is a complication of valvulectomy alone without valve replacement, but also
      may cure the infection. For left-sided disease, surgery is recommended if blood
      cultures remain positive for 7 days on appropriate antimicrobial therapy or if
      Pseudomonas bacteremia recurs after completion of a 6-week course of the combined
      regimen.

PMID- 19745689
TI  - Prevalence and predictors of hepatic steatosis in adults with newly diagnosed
      chronic liver disease due to hepatitis C.
AB  - Obesity appears to be a risk factor for hepatic steatosis, which has been
      implicated in the development of hepatic fibrosis in patients with hepatitis C
      virus infection. We conducted the current study to examine whether obesity is
      associated with hepatic steatosis among patients with chronic hepatitis C
      identified from a population-based cohort. Study participants were persons with
      chronic hepatitis C who had had a liver biopsy, identified from a population
      based study of persons with newly identified chronic liver disease conducted in
      gastroenterology practices. Data were collected through patient interviews,
      medical record abstraction, and review of previously performed liver biopsies.
      The outcome variable of interest was significant steatosis, defined as steatosis
      grade > or =2 determined from liver biopsy samples. Univariate and multivariate
      analyses were performed using logistic regression techniques. The analysis
      included 450 patients with chronic hepatitis C with available liver biopsy
      slides. Overall, only 15.8% of subjects had significant hepatic steatosis (grade
      > or =2), while 35.9% of obese subjects had significant steatosis. In
      multivariate analysis, significant fibrosis (defined as > or = grade 2) (odds
      ratio [OR], 3.43; 95% confidence interval [CI], 1.59-7.37), obesity (OR, 3.32;
      95% CI, 1.84-5.98), genotype 3 (OR, 2.5; 95% CI, 1.09-5.75), and the presence of
      multiple metabolic comorbidities (OR, 1.91; 95% CI, 0.88-4.11) were independently
      associated with steatosis. In this unique United States cohort of patients with
      newly diagnosed chronic liver disease due to hepatitis C, obesity was
      independently associated with hepatic steatosis. The results of this study
      provide additional evidence that obesity worsens liver damage in patients with
      chronic hepatitis C, and suggest a role for weight loss as a treatment modality
      in these patients.

PMID- 19745690
TI  - Clinical risk stratification in the emergency department predicts long-term
      cardiovascular outcomes in a population-based cohort presenting with acute chest
      pain: primary results of the Olmsted county chest pain study.
AB  - The long-term cardiovascular outcomes of a population-based cohort presenting to
      the emergency department (ED) with chest pain and classified with a clinical risk
      stratification algorithm are not well documented. The Olmsted County Chest Pain
      Study is a community-based study that included all consecutive patients
      presenting with chest pain consistent with unstable angina presenting to all EDs
      in Olmsted County, Minnesota. Patients were classified according to the Agency
      for Health Care Policy and Research (AHCPR) criteria. Patients with ST elevation
      myocardial infarction and chest pain of noncardiac origin were excluded. Main
      outcome measures were major adverse cardiovascular and cerebrovascular events
      (MACCE) at 30 days and at a median follow-up of 7.3 years, and mortality through
      a median of 16.6 years.The 2271 patients were classified as follows: 436 (19.2%)
      as high risk, 1557 (68.6%) as intermediate risk, and 278 (12.2%) as low risk.
      Thirty-day MACCE occurred in 11.5% in the high-risk group, 6.2% in the
      intermediate-risk group, and 2.5% in the low-risk group (p < 0.001). At 7.3
      years, significantly more MACCE were recorded in the intermediate-risk (hazard
      ratio [HR], 1.91; 95% confidence intervals [CI], 1.33-2.75) and high-risk groups
      (HR, 2.45; 95% CI, 1.67-3.58). Intermediate- and high-risk patients demonstrated
      a 1.38-fold (95% CI, 0.95-2.01; p = 0.09) and a 1.68-fold (95% CI, 1.13-2.50; p =
      0.011) higher mortality, respectively, compared to low-risk patients at 16.6
      years. At 7.3 and at 16.6 years of follow-up, biomarkers were not incrementally
      predictive of cardiovascular risk.In conclusion, a widely applicable rapid
      clinical algorithm using AHCPR criteria can reliably predict long-term mortality
      and cardiovascular outcomes. This algorithm, when applied in the ED, affords an
      excellent opportunity to identify patients who might benefit from a more
      aggressive cardiovascular risk factor management strategy.

PMID- 19745693
TI  - Efficacy and toxicity of belotecan with and without cisplatin in patients with
      recurrent ovarian cancer.
AB  - OBJECTIVE: This study was performed to determine the safety and efficacy of
      belotecan, a new camptothecin analogue and potent topoisomerase I inhibitor, with
      and without platinum in patients with recurrent ovarian cancer. METHODS: Fifty
      three patients with recurrent or persistent ovarian cancer were enrolled between
      March 2005 and March 2008. Eligible patients received 0.5 mg/m of intravenous
      (IV) belotecan on days 1 to 5, every 3 weeks belotecan monotherapy (B) or 50 mg/m
      of IV cisplatin on day 1 plus 0.3 mg/m of IV belotecan on days 1 to 5, every 3
      weeks (belotecan plus cisplatin combination therapy [BP]). RESULTS: Of the 53
      treated patients, 34 received BP and 19 received B. Thirty-four patients had
      platinum-sensitive (PS) disease and 19 had platinum-resistant disease. The
      overall response of the 53 patients was 37.7% (20/53). According to regimen, the
      response rate in the BP group was 47.1% (16/34) and that of the B group was 21.1%
      (4/19). BP had better response (66.7%, 14/21) than B (15.4%, 2/13) for PS disease
      (P = 0.004), but it was not superior in terms of progression-free survival (BP, 6
      month; B, 7 months). Grade 3 or 4 toxicity was less common in B than in BP.
      CONCLUSION: Both BP and B seems to be effective and safe regimens for patients
      with PS or platinum-resistant recurrent ovarian cancer. These results warrant
      further prospective randomized trials. Both BP and B seems to be effective and
      safe regimens for patients with PS or platinum-resistant recurrent ovarian
      cancer.

PMID- 19745694
TI  - Frequent dose interruptions are required for patients receiving oral kinase
      inhibitor therapy for advanced renal cell carcinoma.
AB  - OBJECTIVE: Recent advances for patients with advanced or metastatic renal cell
      carcinoma (RCC) have been shown to improve progression-free survival with both
      response rates and disease stabilizing activity. Sorafenib, a multikinase
      inhibitor, and sunitinib, an inhibitor of vascular endothelial growth factor-r
      and platelet-derived growth factor-r, have been approved by the Food and Drug
      Administration since 2005/2006. This retrospective analysis of patients treated
      with both aforementioned kinase inhibitors for advanced RCC presents data related
      to their antitumor effects as well as safety profile with particular attention to
      dose interruption and modification requirements. METHODS: This was a
      retrospective review of patients diagnosed with RCC either with advanced disease
      at initial presentation or after first-line therapy, who received either
      continuous sorafenib 400 mg bid or sunitinib 50 mg Qday for 4 weeks on and 2
      weeks off until disease progression or untoward drug reaction. Tumor response was
      evaluated by response evaluation criteria in solid tumors criteria, and adverse
      events were graded by National Cancer Institute-Common Toxicity Criteria.
      RESULTS: From December 2005 to May 2008, 34 patients were followed. Twenty-two
      patients received sorafenib first line, 10 received sunitinib first line, and 2
      patients received sorafenib as third-line therapy. Twenty-nine were evaluable for
      response rates. There were 10 patients (34%) who had stabilization of disease, 8
      patients (28%) who had a partial response, and 11 patients (38%) who had
      progression of disease. The progression-free survival median was 8 months. Of the
      34 patients evaluable for toxicities, grade 3 or 4 adverse event occurred in 19
      patients (56%). These patients required either dose modifications and/or
      treatment interruptions within an average of the first 2 weeks of treatment.
      Eight patients (24%) required drug discontinuation. Eleven patients (32%)
      required dose reductions, but were able to resume the targeted dose after slow
      dose escalation. Three patients (9%) remain dose reduced for greater than 12
      weeks. CONCLUSIONS: Sorafenib and sunitinib have extended patients' disease-free
      survival by several months; however, the initial grade 3 or 4 adverse event
      presented in the literature appear to have been under-reported. Our experience
      suggests that the first 4 weeks of treatment is the most likely timeframe within
      which drug reactions occur. Therefore, careful monitoring and possibly additional
      clinical visits are warranted during this time period. Although a significant
      percentage of patients require dose modification, many can be restarted and
      titrated up to the targeted dose.

PMID- 19745695
TI  - Perinatal outcomes of a pregnancy complicated by cancer, including neonatal
      follow-up after in utero exposure to chemotherapy: results of an international
      registry.
AB  - OBJECTIVE: Because of few cases at any 1 institution, pooling information on the
      treatment of pregnant women diagnosed with cancer and long-term follow-up of
      their children is important. METHODS: Women diagnosed with cancer between their
      last menstrual period and end of pregnancy were voluntarily enrolled in the
      Cancer and Pregnancy Registry. Details of cancer treatment and pregnancy outcomes
      were collected. Neonatal follow-up is obtained yearly. RESULTS: Two hundred
      thirty-one women were enrolled over a 13-year period. Thirteen women elected
      termination. One hundred fifty-seven neonates were exposed to chemotherapy in
      utero. Mean gestational age at delivery for neonates exposed to chemotherapy was
      35.8 +/- 2.8 weeks, mean birth weight was 2647 +/- 713 g. Six children (3.8%)
      were born with a congenital anomaly. An intrauterine fetal demise and a neonatal
      death occurred in 1 case each (0.7% in each). In 12 cases (7.7%), the neonate
      measured <10% for gestational age at birth. Nine cases (5.8%) delivered
      spontaneously premature. Sixty-seven women did not receive chemotherapy during
      pregnancy and delivered 70 neonates. The mean gestational age at delivery was
      36.5 +/- 3.3 weeks, mean birth weight was 2873 +/- 788 g. Mean neonatal follow-up
      is 3 years postpartum and is provided by cancer type and chemotherapy regimen.
      CONCLUSIONS: In pregnancies exposed to chemotherapy after the first trimester,
      congenital anomalies, preterm delivery, and growth restriction were not increased
      as compared with general population norms. Mean gestational age at delivery was
      not significantly different than neonates who were not exposed to chemotherapy.
      There was a statistical significant difference in the birth weight between
      groups, which may not be clinically significant.

PMID- 19745696
TI  - Prostate cancer modality time trend analyses from 1973 to 2004: a Surveillance,
      Epidemiology, and End Results registry analysis.
AB  - OBJECTIVES: Although specialized (urology/radiotherapy [RT]) databases have been
      used to measure practice patterns in nonmetastatic prostate cancer, the
      Surveillance, Epidemiology, and End Results (SEER) registry has not yet been
      employed for this task in detail. Our objectives were to analyze time trends in
      the use of surgery and RT and type of RT (external beam RT [EBRT], brachytherapy
      [Brachy] or combination EBRT + Brachy [Combo]). METHODS: Eight lakh twenty-three
      thousand two hundred ninety-four patients in the SEER public-use registry (1973
      2004) were identified. Modality time-trend curves were plotted for the whole
      group and by (a) grade (well-differentiated [WD], moderately differentiated [MD],
      and poorly differentiated [PD]) and (b) stage (modified AJCC stage 0-I, stage II,
      and stage III). A nonparametric (Spearman) test was used to assess correlation of
      diagnosis year with (a) percentage use of RT and (b) percentage use of EBRT,
      Brachy, and Combo. RESULTS: RT use steadily increased from 9.1% in 1973 to 26.0%
      in 2004 (P < 0.001). Within RT, EBRT use decreased from 99.3% to 59.3% (P <
      0.001), Brachy use increased from 0.0% to 29.6% (P < 0.001), and Combo use
      increased from 0.0% to 11.1% (P < 0.001). Similar time-trend curves to the
      overall group were observed for all grades and for stage 0 to II patients; stage
      III time trends were somewhat more static. CONCLUSIONS: Our SEER analysis
      demonstrated an expected rise in RT use (and relative increase in Brachy)
      paralleling the rise in evidence for modern EBRT and Brachy efficacy/safety.
      Within stated limitations, these results can serve as national benchmarks to
      assess prevailing referral patterns in a given institution or region.

PMID- 19745698
TI  - HER2 Intermediate Breast Cancers.

PMID- 19745699
TI  - Beta-catenin nuclear labeling is a common feature of sessile serrated adenomas
      and correlates with early neoplastic progression after BRAF activation.
AB  - Recent observations indicate that some sessile serrated adenomas (SSAs) have
      aberrant beta-catenin nuclear labeling, implicating the Wnt pathway in the
      molecular progression of SSAs to colorectal carcinoma. We sought to expand upon
      this finding by characterizing beta-catenin expression in the full spectrum of
      serrated colorectal polyps, and correlating these findings with the genetic
      status of BRAF, KRAS and CTNNB1. Immunolabeling for beta-catenin confirmed the
      presence of abnormal nuclear accumulation in SSAs, with 35/54 (67%) SSAs showing
      nuclear labeling compared with 0/12 hyperplastic polyps. Abnormal nuclear
      labeling was also identified in 4/11 (36%) traditional serrated adenomas (TSAs)
      (P=0.00001). When SSAs were further analyzed with respect to the presence or
      absence of conventional epithelial dysplasia, nuclear beta-catenin labeling was
      seen in 8/27 (29%) SSAs without dysplasia (SSA) but in 27/27 (100%) of SSAs with
      dysplasia (P=0.000001). Sequencing of genomic DNA extracted from a subset of
      hyperplastic polyps, SSAs, SSAs with dysplasia, TSAs and tubular adenomas failed
      to identify any CTNNB1 mutations to account for abnormal beta-catenin nuclear
      labeling. However, abnormal nuclear labeling always occurred in the setting of a
      BRAF V600E mutation, indicating aberrant nuclear labeling occurs on a background
      of BRAF activation. Of interest, all 6 TSAs contained a KRAS mutation confirming
      that SSAs and TSAs are genetically distinct entities. These findings validate
      previous reports implicating activation of the Wnt signaling pathway in SSAs, and
      further indicate that Wnt pathway activation plays a role in the neoplastic
      progression of SSAs and TSAs to colonic carcinoma by mechanisms independent of
      CTNNB1 mutation.

PMID- 19745700
TI  - Papillary squamous cell carcinoma of the head and neck: frequent association with
      human papillomavirus infection and invasive carcinoma.
AB  - Papillary squamous cell carcinoma (SCC) is an uncommon variant of SCC in the
      upper aerodigestive tract. It is most frequently located in the larynx,
      oropharynx, and sinonasal tract, and is more common in older men. Because of its
      complex exophytic papillary architecture, histologic assessment of underlying
      invasion can be challenging. Risk factors and pathogenesis are unclear. We
      reviewed 31 papillary SCCs of the upper aerodigestive tract seen at our
      institution over a 17-year period with respect to p16 immunoreactivity and human
      papillomavirus (HPV) status. Twelve papillary SCCs were associated with invasive
      SCC in their disease course. In our study, more than two-thirds of papillary SCCs
      in the upper aerodigestive tract were immunoreactive with antibody to p16 and 68%
      of those lesions had identifiable high-risk HPV by in situ hybridization. As with
      other HPV-associated SCCs of the upper aerodigestive tract, the majority of HPV
      associated papillary SCCs are oropharyngeal (base of tongue and palatine
      tonsils), although both sinonasal and laryngeal tumors were also associated with
      infection (67% and 33% of cases, respectively). Given the better prognosis of HPV
      associated SCCs of the upper aerodigestive tract, it may be prudent to report the
      p16 and HPV status of these tumors when they are encountered.

PMID- 19745701
TI  - Reversible methotrexate-associated lymphoproliferative disorder resembling
      advanced gastric cancer in a patient with rheumatoid arthritis.
AB  - A 73-year-old woman with rheumatoid arthritis had been treated with weekly low
      dose methotrexate (MTX) for 5 years. She suffered from epigastric discomfort.
      Endoscopic examination revealed a tumor resembling advanced gastric cancer.
      Biopsy specimens showed atypical lymphoid cell infiltration. Immunohistological
      studies showed that these cells were positive for CD30 and CD79a, but not for
      CD15 or CD20. In situ hybridization identified Epstein-Barr virus latency
      associated RNA expression in these cells. Clonally rearranged immunoglobulin
      heavy chain JH gene was not detected by Southern blot analysis. She was diagnosed
      with Epstein-Barr virus-associated polymorphic lymphoproliferative disorder (LPD)
      due to immunodeficiency caused by MTX administration. Cessation of MTX therapy
      led to complete regression of the tumor. To our knowledge, this is the first case
      of spontaneous remission of MTX-associated gastric LPD after discontinuation of
      MTX therapy. Increased awareness is needed on the possible occurrence of LPD
      resembling gastric cancer in rheumatoid arthritis patients treated with MTX.

PMID- 19745702
TI  - Kynurenine and its metabolites--kynurenic acid and anthranilic acid are
      associated with soluble endothelial adhesion molecules and oxidative status in
      patients with chronic kidney disease.
AB  - BACKGROUND: Cellular adhesion molecules and oxidative stress play a role in the
      pathogenesis of atherosclerosis in patients with chronic kidney disease (CKD).
      Recently, it has been postulated that the kynurenine (KYN) pathway could be
      involved in the pathogenesis of atherosclerosis. METHODS: We evaluated the KYN,
      kynurenic acid (KYNA), anthranilic acid (AA), and their relations with cellular
      adhesion molecules: soluble intercellular adhesion molecule-1 (sICAM-1), soluble
      vascular adhesion molecule-1 (sVCAM-1), sE-selectin, sP-selectin, and Cu/Zn
      superoxide dismutase (Cu/Zn SOD) levels as the markers of oxidative stress in the
      population of 132 patients with CKD and 28 healthy controls. RESULTS: Compared
      with the controls, 2 groups of dialyzed patients had significantly increased KYN
      (both P < 0.01), KYNA, AA, sICAM-1, sVCAM-1, and Cu/Zn SOD levels (all P < 0.001,
      respectively). KYN, AA, sICAM-1, and sVCAM-1 concentrations were significantly
      higher in undialyzed patients with CKD compared with healthy subjects (P < 0.001,
      P < 0.01, and both P < 0.05, respectively). sICAM-1 and sVCAM-1 were positively
      associated with KYN (P < 0.0001 and P < 0.01), KYNA (P < 0.05 and P < 0.0001), AA
      (P < 0.01 and P < 0.0001), and with Cu/Zn SOD (both P < 0.0001, respectively) in
      the whole CKD group. The positive relationship existed between sICAM-1, sVCAM-1
      and age, high-sensitivity C-reactive protein, creatinine, and the duration of
      dialysis therapy. Multivariable analysis showed that KYN was a strong independent
      correlate of sICAM-1, whereas Cu/Zn SOD and platelets independently and
      significantly predicted sVCAM-1 in patients with CKD. CONCLUSIONS: This study
      demonstrated that KYN is independently and significantly associated with elevated
      sICAM-1, whereas oxidative status and platelets independently and significantly
      predicted increased sVCAM-1 levels in patients with CKD.

PMID- 19745703
TI  - Clinical-pathological features and prognosis of thrombotic thrombocytopenic
      purpura in patients with lupus nephritis.
AB  - BACKGROUND: We investigated the clinical-pathological features and the prognosis
      of thrombotic thrombocytopenic purpura (TTP) in patients with lupus nephritis
      (LN). METHODS: A retrospective analysis was performed on the clinical
      pathological data and prognosis in 8 patients with LN complicating with TTP.
      RESULTS: Thrombocytopenia and hemolytic anemia, neurologic symptoms, and renal
      dysfunction were the clinical manifestations in 8 patients. Six patients had
      fever. Eight patients presented with rapid progressive glomerulonephritis, and 1
      patient with continuous gross hematuria. The histologic features of the 8
      patients were thrombotic microangiopathy lesions. Immune-suppressive therapies
      were administrated in all patients, and blood purification therapy was applied in
      7 patients. Three cases involved plasma exchange and/or immunoabsorption. Seven
      patients received a median follow-up of 12 months. One patient died, 3 cases
      received peritoneal dialysis, and 1 case failed to follow-up. During follow-up, 1
      case was able to stop peritoneal dialysis, and 1 case changed to hemodialysis.
      The other 3 patients continued with stable renal function. CONCLUSION: The
      patients with LN with TTP have severe clinical-pathological changes. Active
      treatment including renal replacement therapy, plasma exchange, and
      immunoabsorption are promising.

PMID- 19745704
TI  - The sensate medial dorsal intercostal artery perforator flap for closure of
      cervicothoracic midline defects after spinal surgery: an anatomic study and case
      reports.
AB  - Complex cervicothoracic midline defects after spinal surgery are traditionally
      treated with the use of muscle and myocutaneous flaps. The authors introduce the
      sensate medial dorsal intercostal artery perforator flap as an alternative
      treatment for these defects. Following an anatomic study, the use of the flap is
      illustrated with 3 case reports. This well-vascularized flap is easy to harvest
      and causes minimal donor site morbidity. It can provide enough volume to
      obliterate dead space. Inclusion of the cutaneous nerve gives protective
      sensibility to the reconstructed area.

PMID- 19745705
TI  - Textured and smooth breast implants: is there a difference in the chemical
      structure of silicone?: an analysis with fourier transformation infrared and
      attenuated total reflectance spectroscopy.
AB  - Scientific controversy concerning silicone and its biocompatibility has been
      ongoing for the last 10 years. This study on textured and smooth silicone breast
      implant shells using fourier transformation infrared spectroscopy associated with
      attenuated total reflectance cells aimed to identify eventual chemical
      modifications of silicone induced by texturization. The surfaces of 8 new
      implants produced by 2 well-known manufactures have been taken into
      consideration. A sample 1 cm2 has been harvested from the anterior and posterior
      sides of textured and smooth shells. Infrared spectra were then recorded,
      evaluated, and compared with the reference spectrum of pure silicone. Potentially
      reactive groups, known as silanols, were identified, in all shells, intensity
      increasing in textured implants (P < 0.05), whereas no silanols were detected in
      the spectrum of pure silicone. These results suggest that polar groups, present
      in manipulated silicone might influence capsula formation.

PMID- 19745706
TI  - Reconstructing a natural looking umbilicus: a new technique.
AB  - An attractive umbilicus is an essential component of the abdominal wall. It
      defines the midline abdominal sulcus and adds to a shapely abdominal curvature.
      Certain procedures place the umbilicus at risk thus providing a need for a
      neoumbilicus. Three-hundred and twenty cases of abdominoplasties,
      panniculetomies, and TRAM flaps for breast reconstruction were reviewed. Five
      patients underwent an umbilical reconstruction after loss of the native
      umbilicus. A crescent-shaped incision was used to create an inferiorly based skin
      flap. The flap was inset to the abdominal fascia. A small full-thickness skin
      graft was used to form the superior hood. All patients attained an esthetically
      pleasing umbilicus with minimal scarring. No contracture, flap necrosis, or graft
      loss were noted. We present a novel, simple, and reliable technique of umbilical
      restoration. It circumvents the need for external scars and allows for achieving
      a naturally appearing umbilicus.

PMID- 19745707
TI  - Double pedicled perforator flap to close flank defects: an alternative for
      closure of a large lumbar defect after basalioma excision--a case report and
      review of the literature.
AB  - Large defects following resection of skin cancers are sometimes a challenge for
      the reconstructive surgeon. Although skin grafts are considered as the first
      choice for reconstruction of large skin defects at the trunk region, pedicled or
      free flaps provide sometimes a superior functional and aesthetic outcome.
      Perforator flaps represent a valuable option for these patients. The progress in
      understanding the perforator vessel system of the body facilitated the
      development of a plethora of novel pedicled flaps which could be transferred over
      long distances with minimal donor site morbidity. We present a patient suffering
      from a large exulcerated basalioma at the lumbar region. The skin defect after
      excision was reconstructed using a novel concept based on 2 independent pedicled
      perforator flaps, a lumbar artery perforator, and a lateral intercostal artery
      perforator.

PMID- 19745708
TI  - The intramuscular course of the inferior gluteal nerve in the gluteus maximus
      muscle and augmentation gluteoplasty.
AB  - The aim of this study was to elucidate the intramuscular course of the inferior
      gluteal nerve in the gluteus maximus muscle and its association with augmentation
      gluteoplasty. Twenty buttocks of 10 Korean adult cadavers (age range: 47-87, 7
      men and 5 women) were used for the study. The inferior gluteal nerve (IGN) was
      traced from the infrapiriform foramen at the deep surface of gluteus maximus (GM)
      until the nerve thickness became 0.3 mm. The depth of the IGN was measured and
      the relative depth of the nerve was calculated according to the thickness of the
      GM at 15 points. The muscle thickness varied according to its location. The
      medial part (17.1-18.1 mm) was thicker than the lateral (14.5-15.7 mm) or
      inferior parts (14.5-14.7 mm). The IGN runs deep through the GM (59%-82% of
      muscle thickness). Except for below the Coccyx-Greater trochanter line, where the
      IGN was located (59%-62% depth), the IGN was traced to 63-82% of the depth in the
      GM. The IGN ran relatively superficial (below 70%) in the medial part of the GM,
      and was a little deeper (above 70%) in the lateral part. There results of this
      study showed that intramuscular augmentation gluteoplasty could be performed
      safely unless intramuscular dissection is performed too deeply.

PMID- 19745709
TI  - Evolution of the pedicled TRAM flap: a prospective study of 500 consecutive cases
      by a single surgeon in Asian patients.
AB  - Although free flap has largely replaced pedicled transverse rectus abdominis
      musculocutaneous (TRAM) flap, the latter has also evolved by increased
      understanding of anatomy and physiology. We report the outcomes in 500
      consecutive pedicled TRAM in Asian patients performed by a single surgeon,
      providing incidences of complications and ideas of prevention. Fascia was
      minimally harvested with full width of muscle. The eighth intercostals nerve was
      severed and back-cut was made at the lateral belly. Anterior rectus sheath was
      directly repaired. Breast complication occurred in 24.6% with the most common
      being skin envelope necrosis. Major flap loss occurred in 1 (0.2%), and the
      incidence of fat necrosis was 14.2%. Abdominal complication rate was 16.4%, and
      bulging occurred in 3%. Exercise performance was almost completely restored after
      1 year. Pedicled TRAM is still a competitive procedure with overall flap survival
      rate of 99.8%, yielding consistent results with acceptable complication rates for
      most patients under experienced hands.

PMID- 19745710
TI  - Refining the intrinsic chimera flap: a review.
AB  - Reconstruction of complex tissue deficiencies in which each missing component is
      in a different spatial relationship to each other can be particularly
      challenging, especially in patients with limited recipient vessels. The chimera
      flap design is uniquely suited to reconstruct these deformities. Chimera flaps
      have been previously defined in many ways with 2 main categories: prefabricated
      or intrinsic. Herein we attempt to clarify the definition of a true intrinsic
      chimeric flap and provide examples of how these constructs provide a method for
      reconstruction of complex defects. The versatility of the intrinsic chimera flap
      and its procurement from 7 different vascular systems is described. A
      clarification of the definition of a true intrinsic chimera flap is described. In
      addition, construction of flaps from the lateral femoral circumflex, deep
      circumflex iliac, inferior gluteal, peroneal, subscapular, thoracodorsal, and
      radial arterial systems is described to showcase the versatility of these chimera
      flaps. A true intrinsic chimera flap must consist of more than a single tissue
      type. Each of the tissue components receives its blood flow from separate
      vascular branches or perforators that are connected to a single vascular source.
      These vascular branches must be of appropriate length to allow for insetting with
      3-dimensional spatial freedom. There are a multitude of sites from which true
      intrinsic chimera flaps may be harvested.

PMID- 19745711
TI  - Bilateral sciatic nerve axonotmesis after gluteal lipoaugmentation.
AB  - The number of lipoaugmentation procedures, and specifically the number of gluteal
      lipoaugmentations, has risen dramatically over the past decade. Though gluteal
      lipoaugmentation confers a pleasing hourglass profile with seemingly minimal
      risk, its risks have not been fully realized. We report the case of a healthy 35
      year-old woman who suffered axonotmesis of the sciatic nerve due to direct
      lipoinjection into and around the nerve sheath. She was treated expectantly in
      our Peripheral Nerve Clinic for 3 months without evidence of improvement.
      Subsequently, she underwent internal and external neurolysis. Eighteen weeks
      after her neurolysis, she continues to demonstrate signs of severe peripheral
      neuropathy, but has begun to show signs of nerve regeneration. This is the first
      reported case of sciatic nerve axonotmesis due to gluteal lipoaugmentation. It
      highlights the importance of a thorough knowledge of gluteal anatomy and a
      consciousness of the risks involved with lipoaugmentation of deep structures.

PMID- 19745712
TI  - Semirigid fixation of mandible and maxilla in orthognathic surgery: stability and
      advantages.
AB  - Although the use of rigid fixation of bony segments in orthognathic surgery has
      become a standard of care, the question remains, 'With use of rigid fixation has
      stability of common orthognathic surgical procedures improved?' Because of the
      problems with various methods of osteosynthesis for the osteotomies commonly used
      in orthognathic surgery, we have developed our own way of semirigid fixation
      method to stabilize the osteotomized fragments for bone healing with enough
      flexibility to avoid the problems arising from absolute rigid fixation. The
      purpose of this article is to review the existing data to determine whether our
      method of semirigid fixation yields enough short-term and long-term stability
      after orthognathic surgery procedures. The study was designed as a retrospective
      trial. A total of 23 patients with double jaw surgery and 12 patients with
      mandibular set back surgery were reviewed. Preoperative lateral cephalometric
      radiographs obtained 1 month before the surgery, early postoperative
      cephalometric radiographs obtained after intermaxillary fixation was opened and
      late postoperative cephalometric radiographs were evaluated. Pog-McNamara
      vertical (mm) was used to measure the anteroposterior movement of mandible.
      Facial axis (degrees) was used to measure the vertical movement of the anterior
      part of the mandible. A-McNamara vertical (mm) was used to measure the
      anteroposterior movement of maxilla. Maxillary height (degrees) was used to
      measure rotational movement of the osteotomized maxillary segment in vertical
      dimension. The raw data obtained from cephalometric analysis were evaluated by
      using the computerized statistical program SPSS version 11.5 for Windows. The
      differences in linear and angular measurements between time intervals were tested
      for statistical significance, using repeated measures analysis of variance. A
      value of P < 0.05 was considered significant. None of the patients had infection
      at maxillary osteotomy side. Unilateral local infection at osteotomy side was
      seen in only one patient after double jaw surgery. Condylar malpositioning was
      not observed in any of the patients. Although postoperative maxillaomandibular
      fixation with elastics was applied routinely to all patients for 15 days, none of
      the patients had complaint related with temporomandibular joint discomfort, such
      as pain, restricted joint motion, etc. There is significant difference in
      anteroposterior movement of mandible in all time intervals. In terms of facial
      axis, the differences at T1 and T2 and at T2 and T3 are significant, while the
      difference at T1 and T3 is not significant. There is significant difference in
      anteroposterior movement of maxilla in all time intervals. In terms of maxillary
      height, the differences at T1 and T2 and at T2 and T3 are significant, while the
      difference at T1 and T3 is not significant. Method of semirigid fixation with 2
      plates for maxillary fixation and 2 screws for mandibular fixation provide enough
      stability after LeFort I and bilateral sagittal split osteotomy procedures where
      mainly anteroposterior linear displacements were performed. There was no
      significant clinical short-term or long-term relapse. Stability in rotational
      movements needs to be further evaluated.

PMID- 19745713
TI  - Sensorimotor recovery after partial facial (mystacial pad) transplantation in
      rats.
AB  - Most research in facial transplantation has been conducted in rats. This skill
      demanding model has a steep learning curve and is accompanied by high mortality
      rates. Investigations were carried out to minimize these disadvantages and a
      whiskers flap properly named mystacial pad flap, was developed. The mystacial pad
      contains the whiskers follicles of the rat, and our aim was to investigate the
      effect of repairing the nerves on the whiskers function after mystacial pad
      allotransplantation in rats. A total of 56 animals were studied in 6 groups. In
      the main study group (VI), 16 semi-allogenic vascularized mystacial flaps were
      transplanted from Lewis-Brown-Norway (RT1(l+n)) to Wistar-Lewis (RT1(l)) rats.
      This group was divided in 2 subgroups; in subgroup VIa (nonneurotized alloflap
      transplant group, n = 8), alloflaps were transplanted without nerve repairs,
      whereas in subgroup VIb (neurotized alloflap transplant group, n = 8) the facial
      and trigeminal nerves were repaired. Animals were kept under tapered doses of
      tacrolimus immunosuppression monotherapy. Clinical and neurophysiological
      explorations were performed to evaluate sensitivity and motor voluntary activity
      of the mystacial region after 6 weeks. Animals were euthanized after 8 weeks and
      histologic studies were performed. In group VI, each procedure required an
      average of 3.5 hours, and 87.5% of the recipients survived for 8 weeks.
      Sensitivity, motor activity, and histologic signs of recovery were found in the
      mystacial pad allotransplants after 6 weeks. Mystacial pad allotransplants in
      which nerves were repaired showed clinical, neurophysiological, and histologic
      signs of recovery. A functional facial subunit was successfully transplanted and
      sensorimotor function recovery could be demonstrated in rats.

PMID- 19745714
TI  - Reconstruction of a "double pathology" on a soft palate: hairy polyp and cleft
      palate.
AB  - Hairy polyps of the head and neck are rare congenital tumors that may cause upper
      aerodigestive tract impairment in newborn. Although cleft palate is a common
      congenital anomaly, hairy polyp with cleft palate is extremely rare in the
      newborn. We aimed to present the planning of reconstruction in a patient who has
      an incomplete cleft palate and defect due to hairy polyp excision on soft palate
      in this report. A 9-month-old child was admitted to our clinic due to cleft
      palate. In the clinical examination, incomplete cleft palate plus a defect on the
      posterior side of the left soft palate was observed. On the history, the patient
      had been operated urgently at the newborn period for a hairy polyp localized on
      the left soft palate which had obstructed the airway. Wardill-Kilner-Veau
      technique was modified for the reconstruction of the defect on the soft palate
      and incomplete cleft palate. No complication was seen on postoperative period.
      The speech ability was evaluated on the late postoperative controls after 3 years
      and adequate speech intelligibility was obtained. A case of hairy polyp of
      nasopharynx with incomplete cleft palate in a neonate and its reconstruction
      techniques are discussed. The etiology of hairy polyp, hamartoma, teratoma,
      dermoid cyst and epignathus, their nomenclature, histopathology, clinical
      features, and management in neonates are also discussed briefly.

PMID- 19745715
TI  - The island anterior intercostal artery perforator flap as another option for the
      difficult epigastric abdominal wound.
AB  - Closure of the epigastric or upper abdominal wound can be challenging even with
      traditional flap options. If those are unavailable due to prior surgical or
      anatomic constraints, a local muscle perforator flap based on the anterior
      intercostal artery (AICA) may be another available option if a vascularized flap
      is mandatory. Caution must be observed as the perforators of the AICA are
      diminutive, and the dissection can be tedious. Nevertheless, in 2 clinical cases,
      the anterior intercostal artery perforator (AICAP) flap was successfully used as
      an island pedicled flap to close a difficult subxiphoid wound, proving a
      secondary role for this donor site as a potential alternative selection.

PMID- 19745716
TI  - The effect of the Botulinum toxin-A on craniofacial development: an experimental
      study.
AB  - In this study, we developed a novel experimental model to evaluate muscular
      action on bone formation and remodeling by the help of Botulinum toxin-A (BTX).
      Forty-nine 15-day-old male Wistar rats were put into 4 groups randomly. Group 1
      was the control group. BTX 0.4 IU (0.05 mL) was injected into the right masseter
      muscle in group 2 and into right temporalis muscle in group 3. The same volume of
      sterile saline was given into the both above-mentioned muscles in group 4. At the
      end of the fourth month, all animals were killed. Histology and weight of the
      masseter and temporalis muscles were studied. Thirty different osteometric
      measurements were also taken from skulls. Significant atrophy in BTX injected
      muscles was observed in groups 2 and 3. In group 4 (saline injection), only few
      osteometric measurements were significantly reduced, indicating the effect of the
      injection itself. Both groups 2 and 3 have apparent decrease in nasal bone,
      premaxilla, maxilla, and zygomatic dimensions on the injected side. When masseter
      group was compared with control and saline groups, no significant difference was
      found in skull base dimensions and mandibular length. In contrast, temporal group
      has also shown significant decrease in skull base dimensions. Our conclusions are
      as follows: (1) With this model, it is possible to study muscular action on bone
      formation and modeling without any surgical intervention, that is, by avoiding
      surgical artifacts, such as scar and contracture; (2) denervation of the skeletal
      muscles with BTX during the growing phase does effect bone development in a
      negative way; (3) pediatric use of the BTX deserves reevaluation under the light
      of these findings.

PMID- 19745717
TI  - Juvenile gigantomastia of extreme magnitude: a case report.

PMID- 19745718
TI  - Parry-Romberg syndrome: facial atrophy and its relationship with other regions of
      the body.
AB  - Parry-Romberg syndrome (PRS) is an uncommon disorder and characterized by a
      slowly, an acquired progressive atrophy involving skin, soft tissue, cartilage,
      and bony structures. Accompanying atrophies of the other parts of the body are
      rarely reported. The aim of this study is to report a case that had contralateral
      lower extremity atrophy with PRS, and to review the related etiologic features,
      physiopathology, and mechanism. The patient who admitted for his facial atrophy
      also had atrophy of his contralateral extremity. This extremity was also short in
      length when compared with other extremity. To obtain detailed information
      regarding the severity of involvement routine laboratory investigations including
      antinuclear antibody (ANA), magnetic resonance imagine (MRI) of the craniofacial
      region and lower extremities, MR angiography of the lower extremities and brain,
      3-dimension computed tomography (CT) scan of the craniofacial region were
      performed. Normal or negative laboratory findings included results of blood
      count, renal and hepatic function biochemical tests, rheumatoid factor, C
      reactive protein, anti-dsDNA antibody except ANA that were positive. His lower
      extremity and brain MR angiography were normal. In the 3-dimensional cranial CT,
      there was no abnormality or defect in the bony structures. His brain MRI showed
      no pathologic changes, and his facial MRI demonstrated noteworthy atrophy to the
      sternocleidomastoid, masseter, pterygoid muscles, and subcutaneus soft tissues on
      the right side of the face. Additionally, MR investigation of his lower
      extremities revealed decreased volume in muscles and bony structures of the
      effected extremity compared with the other extremity, but pathologic evidence of
      fatty degeneration associated with muscle atrophy was not demonstrated. The
      patient had isolated contralateral lower extremity involvement combined with
      hemifacial atrophy (without affecting any other part of the body). Although more
      accepted theory is the sympathic nervous system dysfunction, autoimmunity may
      play a roll in the etiology of our case as ANA abnormality was found in multiple
      tests.

PMID- 19745719
TI  - A phase II study of intra-arterial chemotherapy of 5-fluorouracil, cisplatin, and
      mitomycin C for advanced nonresectable gastric cancer.
AB  - The best choice of chemotherapy regimen for patients with advanced gastric cancer
      (AGC) is still a matter of controversy and requires further investigation. This
      study was performed to evaluate the efficacy and safety of intra-arterial
      infusion chemotherapy of 5-fluorouracil 1000 mg/m, cisplatin 50 mg/m, and
      mitomycin C 10 mg/m (FCM) repeated every 6 weeks, as first-line treatment for
      AGC. Forty-seven (95.9%) of the 49 patients were assessable for response. Four
      cases of complete response and 28 cases of partial response were confirmed,
      giving an overall response rate of 65.3% [95% confidence interval (CI): 52.0
      78.6%]. The median time to progression and overall survival for all patients was
      8.3 months (95% CI: 6.8-9.8 months) and 14.5 months (95% CI: 12.0-17.0 months).
      The estimate of overall survival at 12 and 24 months was 55.1% (95% CI: 41.2
      69.0%) and 18.4% (95% CI: 7.5-29.2%), respectively. Most patients experienced
      neutropenia during their course of therapy with 21.3% of patients (n = 10) for
      grade 3/4 neutropenia. Grade 3 stomatitis, lethargy, and palmar-plantar erythema
      were observed in two (4.3%), eight (17.0%), and one (2.1%) patients,
      respectively. Yet, no grade 4 nonhematological toxicity was observed. Intra
      arterial infusion chemotherapy of 5-fluorouracil 1000 mg/m, cisplatin 50 mg/m,
      and mitomycin C 10 mg/m is a tolerated treatment modality with promising activity
      in patients with previously untreated AGC.

PMID- 19745720
TI  - Triterpenoids as new promising anticancer drugs.
AB  - Triterpenoids are structurally diverse organic compounds, characterized by a
      basic backbone modified in multiple ways, allowing the formation of more than 20
      000 naturally occurring triterpenoid varieties. Several triterpenoids, including
      ursolic and oleanolic acid, betulinic acid, celastrol, pristimerin, lupeol, and
      avicins possess antitumor and anti-inflammatory properties. To improve antitumor
      activity, some synthetic triterpenoid derivatives have been synthesized,
      including cyano-3,12-dioxooleana-1,9 (11)-dien-28-oic (CDDO), its methyl ester
      (CDDO-Me), and imidazolide (CDDO-Im) derivatives. Of these, CDDO, CDDO-Me, and
      betulinic acid have shown promising antitumor activities and are presently under
      evaluation in phase I studies. Triterpenoids are highly multifunctional and the
      antitumor activity of these compounds is measured by their ability to block
      nuclear factor-kappaB activation, induce apoptosis, inhibit signal transducer,
      and activate transcription and angiogenesis.

PMID- 19745721
TI  - Effect of artesunate on immune cells in ret-transgenic mouse melanoma model.
AB  - The antimalarial artesunate also exerts profound cytotoxicity toward tumor cells.
      Earlier investigations controversially discussed a possible immunosuppressive
      function of artemsinin and its derivatives. This poses the question, whether
      immunosuppressive activity counteracts the anticancer activity in vivo. To
      clarify this issue, we used a transgenic mouse spontaneous melanoma model, in
      which ret transgene is expressed in melanocytes under the control of
      metallothionein-I promoter. ret-transgenic mice were previously reported to
      accumulate melanoma-specific effector memory T cells and natural killer (NK)
      cells in the primary tumors and metastatic lymph nodes. In the present
      investigation, we monitored effects of artesunate on the CD4 and CD8 T cells as
      well as Treg and NK cells from ret-transgenic tumor-bearing mice and
      nontransgenic littermates in vivo. In addition, we investigated cytostatic and
      cytotoxic activity of artesunate on ret-tumor cells established from the mouse
      primary tumor. Artesunate inhibited growth of ret-tumor cells and induces their
      apoptosis in a concentration-dependent manner (0.1-200 micromol/l). Furthermore,
      we did not find considerable effects of artesunate on the immune function as
      measured by major cell populations of the immune system; that is, CD4 and CD8 T
      cells as well as Treg and NK cells both from ret-transgenic mice and
      nontransgenic C57BL/6 littermates treated for 2 weeks with a daily dose of 1 mg
      artesunate. These results indicate that the cytostatic and apoptotic effects of
      artesunate are not diminished by concomitant immunosuppression.

PMID- 19745722
TI  - Sex and cannabinoid CB1 genotype differentiate palatable food and cocaine self
      administration behaviors in mice.
AB  - Both cannabinoid CB1 receptor knockout and antagonism produce well-established
      attenuation of palatable food and drug self-administration behavior. Although
      cannabinoid drugs have received attention as pharmacotherapeutics for various
      disorders, including obesity and addiction, it is unclear whether these agents
      produce equivalent behavioral effects in females and males. In this study,
      acquisition of 32% corn oil or 10% Ensure self-administration, and maintenance of
      corn oil, Ensure, or 0.56 mg/kg/infusion cocaine self-administration under both
      fixed ratio (FR)-1 and progressive ratio (PR) schedule of reinforcement, was
      compared in male and female wild type (WT) and CB1 knockout (KO) mice.
      Furthermore, the effect of pretreatment with the CB1 antagonist SR141716 (0.3
      3.0) on Ensure self-administration in male and female WT and CB1 KO mice was
      assessed. CB1 genotype and sex significantly interacted to produce an attenuation
      of acquisition and maintenance of Ensure self-administration and PR self
      administration for both Ensure and cocaine in male CB1 KO mice. In contrast, male
      CB1 KO mice showed no deficit in acquisition and maintenance of FR-1 responding
      or in PR responding maintained by corn oil. Sex differences also arose within
      genotypes for responding maintained under all three reinforcers. Lastly,
      pretreatment with SR141716 attenuated Ensure self-administration in WT and CB1 KO
      mice but was approximately five-fold more potent in WT mice than in CB1 KOs. The
      present data add to a small but growing literature suggesting that the
      cannabinoid system may be differentially sensitive in its modulation of
      appetitive behavior in males versus females.

PMID- 19745723
TI  - Antidepressant-like effects of rosiglitazone, a PPARgamma agonist, in the rat
      forced swim and mouse tail suspension tests.
AB  - Several studies have evaluated thiazolidinedione therapy as medical treatments
      for some central nervous system disorders, such as cognitive deficits associated
      with neurodegenerative disorders. However, there is limited data to support a
      direct role for peroxisome proliferator-activated receptor-gamma agonists in
      depression. Therefore, the aim of this study was to investigate antidepressant
      like activity of rosiglitazone using the mouse tail suspension test and the rat
      forced swimming test, two models sensitive to the effects of antidepressants. In
      the tail suspension test, 5 days of treatment with rosiglitazone (8.5 or 17
      mg/kg, orally) reduced immobility time. In the forced swimming test,
      rosiglitazone (6 or 12 mg/kg, orally) treatment decreased immobility time and
      increased climbing. These effects were not accompanied by any alteration in
      locomotor activity in the open field test. Rosiglitazone treatment (6 or 12
      mg/kg, orally) significantly reduced plasma corticosterone levels in rats. GW9662
      significantly inhibited the rosiglitazone-induced reduction in the duration of
      immobility. In summary, this study suggests that rosiglitazone possesses a
      specific antidepressant-like activity in behavioral models and that this effect
      may be mediated by reduction of plasma corticosterone level.

PMID- 19745724
TI  - Home blood pressure has a stronger association with arterial stiffness than
      clinic blood pressure: the Finn-Home Study.
AB  - OBJECTIVES: Most of the earlier studies assessing the determinants of pulse wave
      velocity (PWV) have been conducted with conventional clinic blood pressure (BP)
      measurements. The aim of this study was to assess whether PWV is more strongly
      associated with home-measured BP than clinic BP. Other risk factors associated
      with PWV were also investigated. METHODS: The study population was an unselected
      sample of 237 adults aged 45-74 years. The study participants underwent the
      measurement of PWV, clinic BP (mean of two measurements using a mercury
      sphygmomanometer) and home BP (mean of 14 duplicate measurements during 1 week
      using a validated, automatic device). Fasting blood samples for serum lipids and
      glucose were drawn. RESULTS: Pearson's correlation coefficients for PWV and
      home/clinic BP differed significantly in favour of home measurement for systolic
      BP (0.65 vs. 0.50, P < 0.001), diastolic BP (0.51 vs. 0.37, P < 0.001) and pulse
      pressure (0.62 vs. 0.40, P < 0.001). In a linear regression model (R(2) = 0.60, P
      < 0.001), home systolic BP (P < 0.001), age (P < 0.001) and diabetes (P < 0.001)
      were independently associated with increased PWV. The association between home BP
      and PWV increased only slightly with the number of home measurements. CONCLUSION:
      Home BP is one of the most important factors affecting arterial stiffness, a
      strong predictor of cardiovascular risk. Home-measured BP is more strongly
      associated with PWV than is clinic BP, even for a low number of measurements.
      These data support the application of home BP measurement in clinical practice,
      as it seems to produce values that represent true BP better than clinic BP.

PMID- 19745725
TI  - Proposal of a method for the evaluation of inaccuracy of home sphygmomanometers.
AB  - OBJECTIVE: There is no formal protocol for evaluating the individual accuracy of
      home sphygmomanometers. The aims of this study were to propose a method for
      achieving accuracy in automated home sphygmomanometers and to test the
      applicability of the defined method. The purposes of this method were to avoid
      major inaccuracies and to estimate the optimal circumstance for individual
      accuracy. METHODS: The method has three stages and sequential measurement of
      blood pressure is used. The tested devices were categorized into four groups:
      accurate, acceptable, inaccurate and very inaccurate (major inaccuracy). The
      defined method takes approximately 10 min (excluding relaxation time) and was
      tested on three different occasions. RESULTS: The application of the method has
      shown that inaccuracy is a common problem among non-tested devices, that
      validated devices are superior to those that are non-validated or whose
      validation status is unknown, that major inaccuracy is common, especially in non
      tested devices and that validation does not guarantee individual accuracy.
      CONCLUSION: A protocol addressing the accuracy of a particular sphygmomanometer
      in an individual patient is required, and a practical method has been suggested
      to achieve this. This method can be modified, but the main idea and approach
      should be preserved unless a better method is proposed. The purchase of validated
      devices and evaluation of accuracy for the purchased device in an individual
      patient will improve the monitoring of self-measurement of blood pressure at
      home. This study addresses device inaccuracy, but errors related to the patient,
      observer or blood pressure measurement technique should not be underestimated,
      and strict adherence to the manufacturer's instructions is essential.

PMID- 19745726
TI  - Dendritic cells as potential targets for mucosal immunotherapy.
AB  - PURPOSE OF REVIEW: A recent meta-analysis confirmed that sublingual immunotherapy
      represents a safe and efficient alternative to traditional subcutaneous
      immunotherapy in the treatment of allergic rhinitis. However, the immunological
      mechanisms have not been elucidated in detail yet. The current concept postulates
      a Th2/Th1 shift along with tolerance induction. Without doubt, oral mucosal
      antigen-presenting cells such as dendritic cells play a central role as they
      process antigens to initialize and modulate T-cell activation. RECENT FINDINGS:
      Oral mucosal dendritic cells (oDCs) are capable of processing antigen applied on
      mucosal surfaces. The natural pro-tolerogenic character of oDCs has been
      demonstrated by the induction of tolerogenic T cells in response to oDCs
      activated by either externally applied antigens such as ovalbumin or antigens
      originating from commensal bacteria like Toll-like receptor ligands, which have
      been shown to be promising candidates for adjuvants. Nevertheless, the finding of
      relatively low numbers of oDCs within the sublingual region opens the search for
      different allergen application sites within the oral cavity such as the
      vestibular region where higher numbers of oDCs are detectable. SUMMARY: oDCs
      display a natural pro-tolerogenic character, which is suspected to be essential
      for successful sublingual immunotherapy. Further knowledge about oDCs behaviour
      might give rise to new sublingual immunotherapy strategies such as adjuvant
      supplementation.

PMID- 19745727
TI  - Specific immunotherapy with allergen mixes: what is the evidence?
AB  - PURPOSE OF REVIEW: The purpose is to review the published evidence for the use of
      multiallergen mixes in subcutaneous and sublingual immunotherapy. RECENT
      FINDINGS: Data are drawn from published articles and reviews, including a recent
      complete search of the English and non-English literature for publications on
      multiallergen immunotherapy.The problems arising from dilution of extracts and
      degradation of extracts resulting from adding additional extracts to a mixture
      are confirmed. The published literature of the use of multiallergen extracts in
      subcutaneous and sublingual immunotherapy indicates that multiallergen extracts
      are effective when given by injection, but a similar efficacy has not been
      established for them when administered sublingually. SUMMARY: Multiallergen
      extract mixes are probably effective for subcutaneous immunotherapy provided
      attention is paid to the concentration of each allergen in the mix and mixing of
      protease containing extracts with pollen and dander extracts is avoided. Further
      studies are needed to determine if multiallergen mixes are effective in
      sublingual immunotherapy.

PMID- 19745728
TI  - Escort accompanying discharge after ambulatory surgery: a necessity or a luxury?
AB  - PURPOSE OF REVIEW: There is a growing demand for greater efficiency in ambulatory
      surgery. The patient population is increasingly sick which is also undergoing
      more advanced and complex surgery. This creates a danger in discharging patients
      without meeting the criterion of requirement of a responsible adult as an escort
      to accompany the patient home. The purpose of this review is to examine the most
      recent findings to determine whether an escort for patient discharge is
      necessary. RECENT FINDINGS: Recent studies have outlined the risks of discharging
      patients without escort after ambulatory anesthesia. There are three aspects that
      deter discharge of patients without an escort: medication used in general
      anesthetics or sedation; regional anesthesia; and surgical factors. All these can
      affect the cognitive, memory and psychomotor function of the patients, deeming
      them unable to perform normal daily activities such as driving. SUMMARY: Both
      clinicians and patients may have underestimated the risks associated with
      discharging patients without an escort after ambulatory anesthesia. There should
      be greater awareness of this problem. Patient discharge without an escort after
      ambulatory surgery under general anesthesia, sedation or premedication can
      potentially be dangerous and is not recommended.

PMID- 19745729
TI  - Introduction of new monitors into clinical anesthesia.
AB  - PURPOSE OF REVIEW: There are an increasing number of monitors being developed to
      measure physiological parameters during the perioperative period. This review
      provides an overview of some of these new monitors developed for use in clinical
      anesthesia and outlines the potential advantages of each device. Pitfalls
      concerning the introduction of additional monitoring devices and the research
      gaps for introducing these monitors into clinical practice are discussed. RECENT
      FINDINGS: Many novel monitoring technologies have been developed, with invasive
      and noninvasive cardiac output monitoring devices and advanced display
      technologies being especially prominent. Most of the published literature focuses
      on monitor efficacy, whereas issues of technology integration and acceptability
      are given less emphasis. Research on novel display technologies is not integrated
      with the monitor development, nor is the display of new information considered
      during the development of new monitors. SUMMARY: More research is needed on how
      to integrate the newly developed monitors into the clinical context to assist
      information-overloaded anesthesiologists. This is essential to achieve the
      potential benefit of new monitoring devices.

PMID- 19745730
TI  - Retrograde amnesia and malingering.
AB  - PURPOSE OF REVIEW: Malingered anterograde amnesia is a phenomenon that has been
      exhaustively studied, whereas research on retrograde amnesia has tended to focus
      upon functional and organic accounts of impairment. The present review explores
      studies relevant to extending the malingering paradigm to retrograde amnesia.
      RECENT FINDINGS: In the period reviewed, very little work has directly addressed
      the area of malingered retrograde amnesia. Researchers have tended to explain
      apparent 'anomalies' in memory performance or individual presentation, as
      manifestations of unconscious or psychological distress-mediated behaviour. In
      contrast, research with offenders claiming amnesia for their crimes has
      emphasized that malingered retrograde amnesia can be identified with relevant
      assessment methods. Brain imaging work too has begun to clearly describe the
      associated neural processes that underlie deception. It appears that the
      necessary coalescence of insights from clinical neuropsychology, brain imaging
      and neurology has reached a critical moment. SUMMARY: Current and previous
      studies are reviewed that addresses the assessment of malingered retrograde
      amnesia and evidences that a critical moment has been reached.

PMID- 19745731
TI  - The role of muscle biopsy in the age of genetic testing.
AB  - PURPOSE OF REVIEW: The purpose of this review is to discuss the role of muscle
      biopsy in the current age of genetic testing. RECENT FINDINGS: The diagnostic
      approach to patients with suspected genetically determined myopathies has been
      altered by recent advances in molecular diagnostic technologies and by the
      increased number of conditions for which the genetic alterations have been
      identified. Myopathological aspects can narrow down the differential diagnosis
      when the clinical phenotype is not informative enough and can help guide the
      molecular investigation. SUMMARY: Here, we review genetic and myopathological
      aspects of selected genetically determined myopathies.

PMID- 19745732
TI  - Emerging genetic therapies to treat Duchenne muscular dystrophy.
AB  - PURPOSE OF REVIEW: Duchenne muscular dystrophy is a progressive muscle
      degenerative disease caused by dystrophin mutations. The purpose of this review
      is to highlight two emerging therapies designed to repair the primary genetic
      defect, called 'exon skipping' and 'nonsense codon suppression'. RECENT FINDINGS:
      A drug, PTC124, was identified that suppresses nonsense codon translation
      termination. PTC124 can lead to restoration of some dystrophin expression in
      human Duchenne muscular dystrophy muscles with mutations resulting in premature
      stops. Two drugs developed for exon skipping, PRO051 and AVI-4658, result in the
      exclusion of exon 51 from mature mRNA. They can restore the translational reading
      frame to dystrophin transcripts from patients with a particular subset of
      dystrophin gene deletions and lead to some restoration of dystrophin expression
      in affected boys' muscle in vivo. Both approaches have concluded phase I trials
      with no serious adverse events. SUMMARY: These novel therapies that act to
      correct the primary genetic defect of dystrophin deficiency are among the first
      generation of therapies tailored to correct specific mutations in humans. Thus,
      they represent paradigm forming approaches to personalized medicine with the
      potential to lead to life changing treatment for those affected by Duchenne
      muscular dystrophy.

PMID- 19745733
TI  - Nontuberculous mycobacterial disease in transplant recipients: early diagnosis
      and treatment.
AB  - PURPOSE OF REVIEW: Infections due to nontuberculous mycobacterial (NTM)
      infections are increasing and, thus, it is likely that practitioners will see an
      increase in NTM infections in transplant recipients. RECENT FINDINGS: There have
      been few recent comprehensive studies evaluating the epidemiology, diagnosis, and
      treatment of NTM infections in transplant recipients. Most recent studies have
      reported unusual and interesting manifestations of NTM infection. Other studies
      have described the posttransplant outcomes of patients with pretransplant
      cultures that grew NTM and provided recommendations regarding the appropriateness
      of performing transplants in these patients. SUMMARY: Recent studies have
      documented the protean nature of the clinical presentation of NTM infections in
      transplant recipients. These studies, as well as previously published reports,
      highlight the need for a high index of suspicion for clinicians when managing
      transplant patients with unexplained fever, cutaneous lesions, joint infections,
      or radiographic opacities. Early diagnosis of NTM infection and initiation of
      therapy are needed to prevent morbidity and mortality in this vulnerable
      population.

PMID- 19745734
TI  - Oxygenation of islets and its role in transplantation.
AB  - PURPOSE OF REVIEW: To summarize recent studies on the oxygenation of pancreatic
      islets and its role in islet transplantation. RECENT FINDINGS: Pancreatic islet
      cells are highly sensitive to hypoxic conditions. Hypoxia contributes to poor
      islet yield at isolation, as well as inflammatory events and cellular death
      during culture and early posttransplantation. Use of oxygen carriers, such as
      semifluorinated alkanes, during pancreas preservation and gas-permeable devices
      for islet culture and transport has in recent studies proven beneficial. Beta
      cell death can be limited posttransplantation by targeting hypoxia-induced
      cellular pathways that cause apoptotic death. Owing to low revascularization,
      impaired oxygenation seems to prevail in intraportally transplanted islets. Means
      to improve revascularization, oxygenation and function of transplanted islets can
      be achieved not only by stimulating angiogenic factors, but also by decrease of
      angiostatic factors such as thrombospondin-1 in islets for transplantation.
      Moreover, bone-marrow-derived cells, such as mesenchymal stem cells and
      hematopoietic stem cells, can induce or contribute to increased
      revascularization. SUMMARY: Low oxygenation of islets contributes to cellular
      death and dysfunction during preparation of islets for transplantation, as well
      as posttransplantation. Interventions at these different steps to ensure adequate
      oxygenation have the potential to improve the results of clinical islet
      transplantation.

PMID- 19745735
TI  - Pediatric head and neck malignancies.
AB  - PURPOSE OF REVIEW: Although head and neck masses represent a common entity in
      children, malignancy is uncommon. The otolaryngologist may be the first physician
      to see these children, and early recognition of malignancy is of obvious
      importance. This review aims to discuss the cause, diagnosis, investigation,
      treatment options, and prognosis for the most common head and neck malignancies
      of childhood. RECENT FINDINGS: Over recent years, significant developments have
      been made in characterizing the epidemiologic, phenotypic, and genotypic
      variability of childhood head and neck cancers. Improved awareness of tumor
      biology is reflected by more sophisticated diagnostics, estimates of prognosis,
      and an increasing individualization of treatment regimens. SUMMARY: The latest
      evidence for the diagnosis and management of childhood head and neck malignancy
      is summarized. The rarity of these tumors inevitably results in a paucity of high
      level evidence to guide treatment. A combination of translational research from
      tumor biology studies, multicenter clinical trials, and smaller case series and
      case reports will continue to guide new advances in diagnosis and treatment.

PMID- 19745736
TI  - Contemporary assessment and management of congenital cholesteatoma.
AB  - PURPOSE OF REVIEW: Only 2-4% of cholesteatomas presenting to pediatric otologists
      are congenital in origin. Disease severity can range from intratympanic pearls to
      middle ear and mastoid obliteration. Recently, highlighted variations of this
      rare disorder warrant a systematic approach to disease assessment and surgical
      decision making. This review provides a comprehensive method to diagnose and
      manage congenital cholesteatoma based on current literature. RECENT FINDINGS: The
      holding theory of the origin of congenital cholesteatomas is that they arise from
      retained epithelial cell rest. Primary development can vary among sites within
      the middle ear and mastoid. 'Open' and 'closed' varieties have been proposed.
      However, disease severity depends on location, patient age, ossicular integrity,
      and number of anatomic sites involved. These variables have inspired the
      development of staging systems whereby appropriate surgical approaches can be
      designed. Computed tomography (CT) scans are necessary and continue to be the
      best radiographic tool for surgical planning. Over 30% of congenital
      cholesteatomas can be extirpated through a transcanal approach. Involvement of
      the posterior quadrant, over three anatomic subsites, or the mastoid cavity
      obligates standard canal wall-up techniques. Canal wall-down procedures are
      rarely required. SUMMARY: Congenital cholesteatomas frequently extend beyond the
      typically described anterosuperior location of the middle ear. Ossicular
      destruction, mastoid infiltration, and tympanic membrane rupture are encountered
      more frequently than previously thought. Advanced disease predominately occurs in
      older children and requires sophisticated assessment and surgical planning beyond
      removing a simple keratin cyst.

PMID- 19745737
TI  - Recent innovations to improve asthma outcomes in vulnerable children.
AB  - PURPOSE OF REVIEW: Despite overall improvements in asthma care through an
      increasing evidence base, disparities in outcomes of children of ethnic
      minorities and low socioeconomic status are well documented across healthcare
      systems. New interventions to reduce gaps in outcomes among these children are
      continually being evaluated. This article reviews the most relevant and
      influential recent studies. RECENT FINDINGS: A number of interventions aimed at
      vulnerable children with asthma have been successful. Most of these include a
      component of education and self-management. There is some evidence that
      culturally competent care produces improved outcomes, whereas stronger evidence
      exists for multifaceted programs and community health workers providing home
      visits for education and environmental allergen reduction. Targeting children and
      families through school-based programs may be an effective outreach strategy. Use
      of novel technologies such as educational messages on MP3 players shows promise
      in reaching at-risk adolescents. SUMMARY: There are promising strategies proven
      to significantly decrease disparities in asthma among vulnerable children.
      Further research must be performed to elucidate the interventions that produce
      the greatest impact on asthma-related outcomes while being feasible, sustainable,
      and cost-effective.

PMID- 19745738
TI  - Healthcare for children with autism: the Autism Treatment Network.
AB  - PURPOSE OF REVIEW: Autism spectrum disorders (ASDs) are a group of a
      neurodevelopmental disorders affecting social, communicative, and behavioral
      functioning. ASD is a heterogeneous group of disorders, often accompanied by
      associated medical issues. Thus, the development of effective treatments is a
      complex task requiring consideration of diverse etiologic and phenotypic
      characteristics. Recent attention to the diagnosis and treatment of medical
      conditions in ASD children has led to the formation of a new international
      collaboration to improve autism care, the Autism Treatment Network (ATN). RECENT
      FINDINGS: Numerous studies have highlighted the high prevalence of
      gastrointestinal and sleep disorders among ASD children. Problems in
      communication - including being nonverbal - make the diagnosis and treatment of
      these conditions more difficult. Although a number of studies suggest links
      between neurologic impairments and gastrointestinal dysfunction and disordered
      sleep, these relationships remain unproven. Recent work by the ATN has begun the
      development of clinical guidelines in these areas, based on clinical consensus,
      adapting the model developed by the Cystic Fibrosis Foundation. New funding has
      also supported the network's development of a robust clinical research program
      focused on improving the physical health and care of children with ASD. These
      efforts promise more systematic and consistent approaches to diagnosis and
      treatment of these conditions. SUMMARY: Improved understanding of the underlying
      pathology of ASD and associated conditions, and the development of a common
      purpose across multiple treating sites, can improve the consistent and
      coordinated healthcare of children with autism.

PMID- 19745739
TI  - Pediatric neurocritical care: is it time to come of age?
AB  - PURPOSE OF REVIEW: Neurocritical care in adults with life-threatening
      neurological disease is a distinct discipline that has developed out of critical
      care medicine and neurology. This review considers whether it is time for such a
      specialized service to be developed in pediatrics. RECENT FINDINGS: Recent
      reports describe how some institutions and pediatric professional bodies have set
      about transferring the specialist neurocritical care experience in adults to
      pediatric practice. The issue, now, is whether such a development would improve
      pediatric healthcare, medical education and training in the newly defined field.
      Adult neurocritical care did not develop in a void. The historical influences
      were the polio epidemics and the investment in experimental neuroprotection.
      These traditions provided a foundation for success in recent clinical trials,
      patient outcomes and healthcare research. Pediatric neurocritical care does not
      have the equivalent parallels and track record in healthcare research. Size of
      practice and casemix is also significantly different, with one-third of potential
      beneficiaries of the new field having a primary medical, rather than
      neurological, disorder. Three types of development for pediatric neurocritical
      services are, therefore, suggested by the literature and the implications of
      these on cross-discipline staffing and education are discussed. SUMMARY:
      Pediatric neurocritical care is the new frontier for pediatric critical care
      medicine and pediatric neurology. There is sufficient specialist interest and
      momentum for the development of a multidisciplinary collaboration that has the
      aim of improving patient care.

PMID- 19745740
TI  - Surgical advances in the treatment of adults with congenital heart disease.
AB  - PURPOSE OF REVIEW: This article reviews three common abnormalities requiring
      surgical treatment in adults with congenital heart disease (CHD): Ebstein's
      anomaly, the failing Fontan, and pulmonary valve disease. RECENT FINDINGS: As of
      2000, more adults than children are alive with CHD. Each year, more of these
      adults with CHD undergo surgery. Three common operations performed on adults with
      CHD are surgery for Ebstein's anomaly, Fontan revision, and pulmonary valve
      replacement (PVR). Recent advances have been made in each of these three
      operations. SUMMARY: Surgery for Ebstein's anomaly can now be offered to older
      patients at low risk and with good late outcome. The operation includes tricuspid
      valve repair or replacement and frequent concomitant procedures such as atrial
      septal defect closure, arrhythmia surgery (the maze procedure), and coronary
      artery bypass grafting. Fontan conversion involves: conversion of the previously
      created atriopulmonary connection to a total cavopulmonary artery, extracardiac
      Fontan; arrhythmia surgery, typically with a modified biatrial maze procedure
      along with placement of an antitachycardia, dual-chamber pacemaker with steroid
      eluting epicardial leads in all patients; and concomitant procedures to treat
      associated lesions. The need for PVR is increasing for many adults with CHD. In
      the past, residual defects such as chronic pulmonary regurgitation following
      repair of tetralogy of Fallot were considered benign. Recent evidence suggests
      that pulmonary regurgitation causes significant morbidity, producing right
      ventricular dilatation and dysfunction, exercise intolerance, arrhythmias, and
      sudden death. Multiple options exist for PVR including several recent
      developments such as PVR with a man-made polytetrafluoroethylene bicuspid valve
      and percutaneous PVR.

PMID- 19745741
TI  - Measuring mental healthcare quality in the United States: a review of
      initiatives.
AB  - PURPOSE OF REVIEW: This review article aims to present a systematic overview of
      the current initiatives assessing mental and/or substance use (M/SU) healthcare
      quality in the United States. RECENT FINDINGS: The study found 36 initiatives
      incorporating M/SU indicators with efforts from the federal and state government,
      health plans, nongovernmental and professional organizations. SUMMARY: Although
      there has been much activity in recent years in the development of M/SU
      indicators, efforts have lacked coordination, have focused on limited areas of
      clinical activity, and have not been clearly linked to quality improvement
      activity. The study recommends that the United States government forms an entity
      to better coordinate efforts and address these concerns. Clinicians and provider
      organizations should also increase the use of already developed M/SU indicators
      to improve quality of care delivered.

PMID- 19745742
TI  - Psychiatry for the person.
AB  - PURPOSE OF REVIEW: This review considers much recent work focused around the
      Psychiatry for the Person Programme of the World Psychiatric Association. Yet we
      have also considered the wider medical context, based on recent publications
      familiar to us in the fields of ethics, religion, spirituality and person-centred
      medicine as well as 'medicine of the person' as developed by Tournier. RECENT
      FINDINGS: There is an urgent need for evaluative outcome studies of person
      centred care, including the narratives of service users, rigorous scientific
      methods and new conceptual models; and for a reformulation of the bio
      psychosocial model to incorporate new knowledge in the neurosciences, philosophy,
      anthropology, ethics and theology. SUMMARY: We suggest that a
      biosocial/psychospiritual (BSPS) approach to relationship-based healthcare should
      be more actively considered.

PMID- 19745743
TI  - Comparison of real-ear to coupler difference values in the right and left ear of
      hearing aid users.
AB  - OBJECTIVE: The purpose of this study was to compare real-ear to coupler
      difference (RECD) values in the right and left ear of hearing aid users. DESIGN:
      RECDs were obtained from both ears of 16 adults, 17 school-age children, and 11
      preschool children using the Audioscan Verifit real-ear microphone system.
      RESULTS: In 80 to 90% of participants, the difference between ears was generally
      <3 dB at 0.5 to 4 kHz. CONCLUSIONS: In hearing aid users with nonoccluding wax
      and normal middle ear function, the difference in RECD between the right and left
      ear is small and probably not clinically significant.

PMID- 19745744
TI  - Depression, heart rate variability, and exercise training in dialysis patients.
AB  - BACKGROUND: Functional limitations, altered cardiac autonomic activity, and
      psychological distress are known disorders in chronic hemodialysis (HD) patients,
      relating to increased morbidity and mortality. The aim of this study was to
      examine the influence of an exercise training program on emotional parameters and
      heart rate variability (HRV) indices, as well as to determine whether emotional
      stress contributes to autonomic dysfunction in these patients. METHODS: Forty
      four HD patients were randomly assigned into group A (24 patients, aged 46.3+/
      11.2 years), who participated in a 1-year intradialytic exercise training program
      and group B (20 patients, aged 45.8+/-10.8 years), who were used as controls. At
      baseline and a year after, measures of HRV were obtained for the estimation of
      standard deviation of RR intervals, the mean square successive differences,
      percentage of RR intervals differing by more than 50 ms from the preceding RR
      interval (pNN50), and low to high frequency components. Emotional parameters
      (Beck Depression Inventory - BDI and Hospital Anxiety and Depression Scale -
      HADS) were also assessed by validated questionnaires. Moreover, all patients
      performed a spiroergometric study for the estimation of VO2peak. RESULTS: At
      baseline, all measurements were similar in the two groups and remained almost
      unchanged after a year in group B. After a year of training, VO2peak increased
      from 16.79+/-5.24 to 22.33+/-4.90 ml/kg per min (P<0.001) in group A. Trained
      patients also showed an increase in standard deviation of RR intervals by 58.8%
      (P<0.001), the mean square successive differences by 68.1% (P<0.001), pNN50 by
      23.5% (P<0.001), and a low to high frequency ratio by 17.3% (P<0.001). Finally,
      at the end of the study, group A showed a decrease in BDI score by 34.5%
      (P<0.001) and HADS by 23.9% (P<0.001). Canonical correlation revealed significant
      inverse correlation among depression (in BDI and HADS) and HRV indices before and
      after exercise training. CONCLUSION: Cardiac autonomic modulation seemed to be
      sensitive to the experience of persistent depression in HD patients.
      Significantly, exercise training reduced emotional distress and concomitantly
      improved HRV.

PMID- 19745746
TI  - Life expectancy and cause of death in males and females with Fabry disease:
      findings from the Fabry Registry.
AB  - PURPOSE: To evaluate life expectancy and cause of death among patients with Fabry
      disease, an X-linked lysosomal storage disorder. METHODS: Data from 2848 patients
      in the Fabry Registry were summarized using descriptive statistics. Life
      expectancy at birth was compared with that of the United States general
      population. RESULTS: As of August 2008, 75 of 1422 males and 12 of 1426 females
      in the Fabry Registry were reported to have died. The 87 deceased patients were
      diagnosed at a much older age than other patients in the Fabry Registry: median
      age at diagnosis was 40 vs. 24 years in males and 55 vs. 33 years in females. The
      life expectancy of males with Fabry disease was 58.2 years, compared with 74.7
      years in the general population of the United States. The life expectancy of
      females with Fabry disease was 75.4 years, compared with 80.0 years in the United
      States general population. The most common cause of death among both genders was
      cardiovascular disease. Most (57%) patients who died of cardiovascular disease
      had previously received renal replacement therapy. CONCLUSIONS: Most deceased
      Fabry Registry patients exhibited serious cardiac and renal dysfunction. Late
      diagnosis may have contributed to the early deaths of these patients.

PMID- 19745745
TI  - A randomized, controlled trial of simvastatin versus rosuvastatin in patients
      with acute myocardial infarction: the Secondary Prevention of Acute Coronary
      Events--Reduction of Cholesterol to Key European Targets Trial.
AB  - AIMS: We sought to evaluate reports that rosuvastatin 10 mg is a more efficacious
      treatment of hyperlipidaemia than is simvastatin 40 mg, hoping to assess this
      issue in the previously unstudied context of acute myocardial infarction. METHODS
      AND RESULTS: The Secondary Prevention of Acute Coronary Events - Reduction of
      Cholesterol to Key European Targets (SPACE ROCKET) Trial was an investigator-led,
      open-label, blinded-endpoint, multicentre, randomized, controlled trial assessing
      the proportion of patients, at 3 months, achieving European Society of Cardiology
      2003 (ESC-03) lipid targets of total cholesterol (TC) less than 4.5 mmol/l (174
      mg/dl) or low-density lipoprotein cholesterol (LDLc) less than 2.5 mmol/l (97
      mg/dl). Of 1263 patients randomized, 77.6% simvastatin versus 79.9% rosuvastatin
      achieved ESC-03 targets [odds ratio (OR): 1.16; 95% confidence interval (CI):
      0.88-1.53; P = 0.29]. There were statistically significant differences for
      simvastatin versus rosuvastatin, respectively, for mean LDLc 2.03 mmol/l (78
      mg/dl) versus 1.94 mmol/l (75 mg/dl; P = 0.009) and also mean TC 3.88 mmol/l (150
      mg/dl) versus 3.75 mmol/l (145 mg/dl; P = 0.005). A post-hoc analysis showed
      higher achievement of the new ESC, American Heart Association and American
      College of Cardiology optimal lipid target of LDLc less than 1.81 mmol/l (70
      mg/dl) with rosuvastatin (45.0%) compared with simvastatin (37.8%; OR: 1.37; 95%
      CI: 1.09-1.72; P = 0.007). The proportion of patients achieving the Fourth Joint
      Task Force European Guidelines (2007) of TC less than 4.0 mmol/l (155 mg/dl) and
      LDLc less than 2.0 mmol/l (77 mg/dl) was 38.7% for simvastatin 40 mg and 47.7%
      for rosuvastatin 10 mg (OR: 1.48; 95% CI: 1.18-1.86; P = 0.001). CONCLUSION: We
      observed no superiority of either treatment for the ESC-03 lipid targets.
      Rosuvastatin 10 mg lowered mean cholesterol more effectively than simvastatin and
      achieved better results for the latest, more stringent, ESC target.

PMID- 19745747
TI  - A gene dosage map of Chromosome 18: a map with clinical utility.
AB  - PURPOSE: Microarray technology has revolutionized the field of clinical genetics
      with the ability to detect very small copy number changes. However, challenges
      remain in linking genotype with phenotype. Our goal is to enable a clinical
      geneticist to align the molecular karyotype information from an individual
      patient with the annotated genomic content, so as to provide a clinical
      prognosis. METHODS: We have combined data regarding copy number variations,
      microdeletion syndromes, and classical chromosome abnormalities, with the sparse
      but growing knowledge about the biological role of specific genes to create a
      genomic map of Chromosome 18 with clinical utility. RESULTS: We have created a
      draft model of such a map, drawing from our long-standing interest in and data
      regarding the abnormalities of Chromosome 18. CONCLUSION: We have taken the first
      step toward creating a genomic map that can be used by the clinician in
      counseling and directing preventive or symptomatic care of individuals with
      Chromosome 18 abnormalities.

PMID- 19745748
TI  - A comparison of male attendees and nonattendees at a familial cancer clinic.
AB  - PURPOSE: This retrospective descriptive Australian study aimed to determine
      predictors of nonattendance at a familial cancer clinic by men from high-risk
      breast/ovarian cancer families. METHODS: Two hundred twenty-six men from families
      with a known BRCA1 or BRCA2 mutation were recruited through an epidemiological
      database of high-risk breast cancer families and completed a self-administered
      questionnaire. RESULTS: Multivariate analyses using binary logistic regression
      showed that nonattendance at a familial cancer clinic by men from high-risk
      breast/ovarian cancer families was associated with younger age (51 vs. 55 years)
      (odds ratio = 1.03, P = 0.04) and lower cancer burden (one relative diagnosed
      versus two relatives diagnosed) (odds ratio = 2.6, P = 0.04). CONCLUSION:
      Compared with men who attended a familial cancer clinic, nonattendees were
      younger and had fewer relatives diagnosed with breast/ovarian cancer. Unlike
      previous findings, cancer-specific worry, in particular avoidance was not
      associated with nonattendance. The number, age, and sex of biological children
      were not associated with attendance or nonattendance. Hence, some of the
      assumptions about what makes information on BRCA1 or BRCA2 status salient to men
      and may therefore influence their attendance at a cancer genetic clinic are not
      borne out in this study.

PMID- 19745749
TI  - Disentangling the Babylonian speech confusion in genetic counseling: an analysis
      of the reliability and validity of the nomenclature for BRCA1/2 DNA-test results
      other than pathogenic.
AB  - PURPOSE: Effective communication of DNA-test results requires a sound
      terminology. However, the variety of terms in literature for DNA-test results
      other than pathogenic, may create inconsistencies between professionals, and
      misunderstanding in patients. Therefore, we conducted a theoretical and empirical
      analysis of the terms most frequently used in articles between 2002 and 2007 for
      BRCA 1/2-test results other than pathogenic. DESIGN: We analyzed the content
      validity of the no-pathogenic DNA-test result-terms by comparing the literal and
      intended meaning of the terms and by examining their clarity and the inclusion of
      all relevant information. We analyzed the reliability of the terms by measuring
      the strength of association between terms and their meanings and the consistency
      among different authors over time. RESULTS: Two hundred twenty-seven articles
      with 361 no-pathogenic DNA-test result-terms were found. Only two terms seemed to
      have acceptable validity: variant of uncertain clinical significance and no
      pathogenic-DNA-test-result. Only variant of uncertain clinical significance and
      true negative were found to be used reliably in the literature. CONCLUSIONS:
      Current DNA nomenclature lacks validity and reliability. Transparent DNA-test
      result terminology should be developed covering both laboratory findings and
      clinical meaning.

PMID- 19745750
TI  - The ethical use of existing samples for genome research.
AB  - Modern biobanking efforts consist of prospective collections of tissues linked to
      clinical data for patients who have given informed consent for the research use
      of their specimens and data, including their DNA. In such efforts, patient
      autonomy and privacy are well respected because of the prospective nature of the
      informed consent process. However, one of the richest sources of tissue for
      research continues to be the millions of archived samples collected by pathology
      departments during normal clinical care or for research purposes without specific
      consent for future research or genetic analysis. Because specific consent was not
      obtained a priori, issues related to individual privacy and autonomy are much
      more complicated. A framework for accessing these existing samples and related
      clinical data for research is presented. Archival tissues may be accessed only
      when there is a reasonable likelihood of generating beneficial and scientifically
      valid information. To minimize risks, databases containing information related to
      the tissue and to clinical data should be coded, no personally identifying
      phenotypic information should be included, and access should be restricted to
      bona fide researchers for legitimate research purposes. These precautions, if
      implemented appropriately, should ensure that the research use of archival tissue
      and data are no more than minimal risk. A waiver of the requirement for informed
      consent would then be justified if reconsent is shown to be impracticable. A
      waiver of consent should not be granted, however, if there is a significant risk
      to privacy, if the proposed research use is inconsistent with the original
      consent (where there is one), or if the potential harm from a privacy breach is
      considerable.

PMID- 19745751
TI  - Use of complementary and alternative medicine by patients with lysosomal storage
      diseases.
AB  - PURPOSE: To evaluate the extent of complementary and alternative medicine use and
      perceived effectiveness in patients with lysosomal storage diseases. METHODS: A
      26-item survey was distributed to 495 patients with type 1 Gaucher, Fabry, and
      type B Niemann-Pick diseases who were seen at the Lysosomal Storage Disease
      Program at the Mount Sinai School of Medicine. Survey responses were entered into
      an access database and analyzed using descriptive statistics. RESULTS: Surveys
      were completed by 167 respondents with an overall response rate of 34%.
      Complementary and alternative medicines were used by 45% of patients with type 1
      Gaucher disease, 41% of patients with Fabry disease, and 47% of patients with
      type B Niemann-Pick for symptoms related to their disease. Complementary and
      alternative medicines were used most frequently by adult females (55%), in
      patients who reported having one or more invasive procedures due to their
      disease, patients who use one or more conventional medical therapies, or those
      with depression and/or anxiety. Overall perceived effectiveness of complementary
      and alternative medicine supplements was low; however, complementary and
      alternative medicine therapies were perceived as effective. CONCLUSION:
      Complementary and alternative medicines are commonly used among patients with
      lysosomal storage diseases. Assessment of the effectiveness of these approaches
      in the lysosomal storage diseases is needed, and physicians should be aware of
      complementary and alternative medicine therapies used by patients to evaluate
      safety and possible drug interactions.

PMID- 19745752
TI  - Sustainability of first-line antiretroviral regimens: findings from a large HIV
      treatment program in western Kenya.
AB  - OBJECTIVE: To describe first change or discontinuation in combination
      antiretroviral treatment (cART) among previously treatment naive, HIV-infected
      adults in a resource-constrained setting. METHODS: The United States Agency for
      International Development-Academic Model Providing Access to Healthcare
      Partnership has enrolled >90,000 HIV-infected patients at 18 clinics throughout
      western Kenya. Patients in this analysis were aged > or =18 years, previously
      antiretroviral treatment naive, and initiated to cART between January 2006 and
      November 2007, with at least 1 follow-up visit. A treatment change or
      discontinuation was defined as change of regimen including single drug
      substitutions or a complete halting of cART. RESULTS: There were 14,162 patients
      eligible for analysis and 10,313 person-years of follow-up, of whom 1376 changed
      or stopped their cART. Among these, 859 (62%) changed their regimen (including
      514 patients who had a single drug substitution) and 517 (38%) completely
      discontinued cART. The overall incidence rate (IR) of cART changes or stops per
      100 person-years was 13.3 [95% confidence interval (CI): 12.7-14.1]. The
      incidence was much higher in the first year of post-cART initiation (IR: 25.0,
      95% CI: 23.6-26.3) compared with the second year (IR: 2.4, 95% CI: 2.0-2.8). The
      most commonly cited reason was toxicity (46%). In multivariate regression,
      individuals were more likely to discontinue cART if they were World Health
      Organization stage III/IV [adjusted hazard ratio (AHR): 1.37, 95% CI: 1.11-1.69]
      or were receiving a zidovudine-containing regimen (AHR: 4.44, 95% CI: 3.35-5.88).
      Individuals were more likely to change their regimen if they were aged > or =38
      years (AHR: 1.44, 95% CI: 1.23-1.69), had to travel more than 1 hour to clinic
      (AHR: 1.34, 95% CI: 1.15-1.57), had a CD4 at cART initiation < or =111 cells/mm3
      (AHR: 1.51, 95% CI: 1.29-1.77), or had been receiving a zidovudine-containing
      regimen (AHR: 3.73, 95% CI: 2.81-4.95). Those attending urban clinics and those
      receiving stavudine-containing regimens were less likely to experience either a
      discontinuation or a change of their cART. CONCLUSIONS: These data suggest a
      moderate incidence of cART changes and discontinuations among this large
      population of adults in western Kenya. Mostly occurring within 12 months of cART
      initiation, and primarily due to toxicity, older individuals, those with more
      advanced disease, and those using zidovudine are at higher risk of experiencing a
      change or a discontinuation in their cART.

PMID- 19745753
TI  - Understanding reasons for and outcomes of patients lost to follow-up in
      antiretroviral therapy programs in Africa through a sampling-based approach.
AB  - OBJECTIVES: Losses to follow-up after initiation of antiretroviral therapy (ART)
      are common in Africa and are a considerable obstacle to understanding the
      effectiveness of nascent treatment programs. We sought to characterize, through a
      sampling-based approach, reasons for and outcomes of patients who become lost to
      follow-up. DESIGN: Cohort study. METHODS: We searched for and interviewed a
      representative sample of lost patients or close informants in the community to
      determine reasons for and outcomes among lost patients. RESULTS: Three thousand
      six hundred twenty-eight HIV-infected adults initiated ART between January 1,
      2004 and September 30, 2007 in Mbarara, Uganda. Eight hundred twenty-nine became
      lost to follow-up (cumulative incidence at 1, 2, and 3 years of 16%, 30%, and
      39%). We sought a representative sample of 128 lost patients in the community and
      ascertained vital status in 111 (87%). Top reasons for loss included lack of
      transportation or money and work/child care responsibilities. Among the 111 lost
      patients who had their vital status ascertained through tracking, 32 deaths
      occurred (cumulative 1-year incidence 36%); mortality was highest shortly after
      the last clinic visit. Lower pre-ART CD4 T-cell count, older age, low blood
      pressure, and a central nervous system syndrome at the last clinic visit
      predicted deaths. Of patients directly interviewed, 83% were in care at another
      clinic and 71% were still using ART. CONCLUSIONS: Sociostructural factors are the
      primary reasons for loss to follow-up. Outcomes among the lost are heterogeneous:
      both deaths and transfers to other clinics were common. Tracking a sample of lost
      patients is an efficient means for programs to understand site-specific reasons
      for and outcomes among patients lost to follow-up.

PMID- 19745754
TI  - Comparison of early CD4 T-cell count in HIV-1 seroconverters in Cote d'Ivoire and
      France: the ANRS PRIMO-CI and SEROCO cohorts.
AB  - OBJECTIVE: We compared CD4+ decline among untreated HIV-1-infected seroconverters
      living in Cote d'Ivoire (CI) and in France. METHODS: HIV-1-infected adults were
      enrolled in the ANRS1220 PRIMO-CI (CI, 1997-2006) and ANRSCO2 SEROCO (France,
      1988-1995) cohorts. CD4+ count and percentage declines were estimated from
      enrollment until 24 months of seroconversion by linear random-effect models
      adjusted for time since seroconversion, age, gender, cell-associated HIV DNA, HIV
      RNA, and country. RESULTS: Overall 521 seroconverters (CI 148, 62% men; France
      373, 77% men) were enrolled after a median of 7.6 months since seroconversion.
      Median follow-up duration was 12.7 months. Median age was 28 years. Median
      baseline CD4+ count was 472 and 560 cells per cubic millimeter, respectively.
      Median baseline HIV RNA was 4.4 and 4.0 log10 copies per milliliter and median
      HIV DNA was 3.0 and 2.8 log10 copies per 10(6) peripheral blood mononuclear
      cells, respectively. In adjusted models, CD4+ count and percentage at baseline
      were lower in CI than in France (P < 0.01), and the difference did not vary
      during follow-up (P = 0.55). Low HIV RNA and low HIV DNA at baseline were
      associated with higher CD4+ count at baseline. CONCLUSIONS: CD4+ count and
      percentage were lower in CI than in France. These differences were already
      observed during early infection and remained similar after adjustment.

PMID- 19745755
TI  - Plasma cytokine levels in Tanzanian HIV-1-infected adults and the effect of
      antiretroviral treatment.
AB  - OBJECTIVE: To evaluate the role immune activation leading to the production and
      circulation of cytokines has in the pathogenesis of HIV infection in sub-Saharan
      Africa and the effect of antiretroviral treatment (ART) on these parameters.
      METHODS: Plasma concentrations of tumor necrosis factor (TNF)-alpha, interleukin
      (IL)-6, IL-8, monocyte chemotactic protein (MCP)-1, IL-10, and IL-1 receptor
      antagonist; plasma HIV RNA; hemoglobin concentration; and white blood cells were
      measured in 229 HIV-infected, 54 HIV-uninfected, and after 2 and 4 months,
      respectively, of ART in 35 eligible individuals in northeastern Tanzania.
      RESULTS: Plasma levels of tumor necrosis factor-alpha, IL-6, IL-8, monocyte
      chemotactic protein-1, and IL-1 receptor antagonist were significantly higher in
      HIV-infected individuals compared with HIV-uninfected individuals and also
      significantly higher in HIV-infected individuals with CD4 cell counts below 200
      cells per microliter than individuals with CD4 cell counts above 200 cells per
      microliter. HIV RNA was the strongest predictor of all cytokine expression in
      multivariate analysis. ART leads to a decrease in all cytokines to levels close
      to those of HIV-uninfected individuals. CONCLUSIONS: Our findings support the
      role of HIV viral replication as the most important promoter of immune activation
      and prove the importance of ART in reducing immune activation and viral
      replication even in sub-Saharan Africa where patients are exposed to an abundance
      of other infectious agents.

PMID- 19745756
TI  - Survival in Asian Americans after treatments for hepatocellular carcinoma: a
      seven-year experience at UCLA.
AB  - BACKGROUND/RATIONALE: Hepatocellular carcinoma (HCC) is a common malignancy in
      Asians and is related to the high incidence of chronic viral hepatitis in this
      ethnic population. The aims of this study were to examine the tumor
      characteristics and liver disease status in HCC patients of Asian ancestry and
      determine their survival after treatments for HCC. RESULTS: Between September
      2000 and December 2007, 278 patients, mean age 61.5 years, presented with HCC to
      the University of California Los Angeles (UCLA) Liver Cancer Center. Hepatitis B
      (HBV) infection was detected in up to 68% of Chinese, Korean, and Vietnamese
      patients, whereas 60% of Japanese patients had Hepatitis C (HCV) infection.
      Compared with HCC patients who presented with symptoms, those detected by
      surveillance had more tumors within the Milan and University of California, San
      Francisco (UCSF) criteria and more patients in Child-Turcotte-Pugh class A. On
      the basis of a predefined UCLA treatment algorithm, 83% of patients received
      surgical and/or loco-regional therapies. Compared with other treatments,
      orthotopic liver transplantation (OLT), and radiofrequency ablation had the
      highest overall patient survival (P<0.0001) and OLT has the highest disease free
      survival rates (P<0.0001). Independent baseline predictors for: (1) patient
      survival were HBV [hazard ratio (HR) 0.62, P=0.005], UCSF criteria (HR 0.46,
      P<0.0001), Child Turcotte Pugh class A (HR 0.57, P=0.005), alphafetoprotein per
      log10 increase (HR 1.26, P=0.0012), and alkaline phosphatase per log10 increase
      (HR 2.32, P=0.02); and for (2) disease free survival were UCSF criteria (HR 0.66
      P=0.007), aspartate aminotransferase per log10 increase (HR 1.50, P=0.04), and
      age per year increase (HR=1.02, P=0.04). The 4 Asian subgroups had similar
      survival rates. CONCLUSIONS: HBV and Hepatitis C were associated with over 90% of
      HCC cases in Asian Americans. HCC detected by surveillance identified more
      patients eligible for surgical and loco-regional therapies, which improved the
      overall and disease free survival.

PMID- 19745757
TI  - Primary low-grade and high-grade gastric MALT-lymphoma presentation.
AB  - GOAL: To assess the clinical and endoscopic presentation of primary gastric
      lymphoma. BACKGROUND: Remission rate and long-term survival in patients with
      gastric lymphoma mainly depend on disease stage at diagnosis. Series reporting
      clinical and endoscopic presentation of gastric lymphoma are generally small and
      heterogeneous. STUDY: Systematic review with pooled-data analysis assessing
      clinical and endoscopic presentation of primary gastric lymphoma. RESULTS: Data
      regarding 2000 patients were collected. Overall, males were slightly more
      prevalent, alarm symptoms were absent in near half of the patients, lymphoma was
      diagnosed in a stage >I in one-third of the patients, and Helicobacter pylori
      infection was present in 88.8% of considered patients. At endoscopy, the
      ulcerative type was the most frequent presentation, although low-grade lymphoma
      was diagnosed on normal/hyperemic gastric mucosa in 9% of cases. Patients with
      high-grade lymphoma presented alarm symptoms (anemia and/or melena and/or
      hemorrhage, persistent vomiting, weight loss), an exophytic or ulcerative lesion,
      a stage III-IV, and a H. pylori negative status more frequently than low-grade
      lymphoma cases. CONCLUSIONS: Our pooled-data analysis showed that gastric
      lymphoma is still disappointingly diagnosed in an advanced stage in a large
      number of patients. This is probably due to presence of nonspecific symptoms at
      initial clinical presentation and/or a normal appearing mucosa at endoscopic
      observation in the early stages.

PMID- 19745758
TI  - A meta-analysis of transient elastography for the detection of hepatic fibrosis.
AB  - OBJECTIVES: The use of transient elastography to assess liver stiffness
      measurement (LSM) has now become widely available for the diagnosis of liver
      fibrosis as a rapid, noninvasive test (it is still not approved for use in the
      United States). It has previously been showed as an accurate method of
      representing the state of liver fibrosis with concomitant evaluation of liver
      biopsy and the histologic scoring system METAVIR. We performed a meta-analysis to
      further assess its use in comparison with liver biopsy. METHODS: Studies from the
      literature were analyzed with a median liver stiffness value in kilopascal given
      for fibrosis stages according to histopathologic findings on biopsy and best
      discriminant cutoff levels in kilopascals for significant fibrosis (>or=F2) and
      cirrhosis (F4). RESULTS: A total of 22 studies were selected comprising 4,430
      patients; chronic hepatitis C infection was the most common etiology of fibrosis.
      The pooled estimates for significant fibrosis (>or=F2) measured 7.71 kPa (LSM
      cutoff value) with a sensitivity of 71.9% [95% confidence interval (CI): 71.4%
      72.4%] and specificity of 82.4% (95% CI: 81.9-82.9%), whereas for cirrhosis (F4)
      the results showed a cutoff of 15.08 kPa with a sensitivity of 84.45% (95% CI:
      84.2-84.7%) and specificity of 94.69% (95% CI: 94.3%-95%). CONCLUSIONS: Further
      evaluation of transient elastography to assess LSM is required in prospective
      studies to potentially increase the sensitivity and establish its clinical
      utility.

PMID- 19745759
TI  - The epidemiology and clinical characteristics of patients with newly diagnosed
      alcohol-related liver disease: results from population-based surveillance.
AB  - GOALS: We describe the epidemiology of outpatients newly diagnosed with chronic
      alcoholic liver disease and describe predictors of cirrhosis and referral for
      specialty care. BACKGROUND: Alcohol is a major cause of liver disease in the
      United States. Most previous work has described hospitalized patients. STUDY:
      Participants were identified through prospective population-based surveillance in
      gastroenterology practices Multnomah County, Oregon and New Haven County,
      Connecticut; and primary care and gastroenterology practices from Kaiser
      Permanente Northern California in Alameda County during 1999 to 2001. Patients
      were interviewed, a blood specimen obtained, and their medical record reviewed.
      RESULTS: We identified 82 patients from gastroenterology practices with newly
      diagnosed alcoholic liver disease. Their median age was 50.0 years. 72.0% were
      male and 79.3% were White. The median age at initiation of alcohol use was 17.0
      years. 43.9% of patients had evidence of cirrhosis at the time of diagnosis. Only
      40.2% reported alcohol as the cause of their liver disease. Patients with
      cirrhosis were more likely to be older, have a higher median number of years of
      heavy alcohol consumption, and to have been hospitalized for a liver-related
      complication than noncirrhotic patients. An additional 83 primary care patients
      were more likely to be older, to be drinking alcohol at study interview, and to
      not have cirrhosis than patients referred for gastroenterology care. CONCLUSIONS:
      Patients with alcoholic liver disease may present at a late stage and may not
      identify alcohol as a cause for their liver disease. Improved patient screening
      and education may limit morbidity and mortality.

PMID- 19745760
TI  - Social and demographic predictors of preschoolers' bedtime routines.
AB  - OBJECTIVE: To examine the associations of child and family sociodemographic
      characteristics with preschooler bedtime routines. METHOD: We use parent-report
      data of 3217 3-year-old children (48% black, 26% Hispanic, and 22% white) from
      the Fragile Families and Child Wellbeing Study to examine whether child and
      family characteristics are associated with the presence, time, and consistency of
      bedtime routines. RESULTS: More than 80% of sample children have a bedtime yet
      only two thirds follow it. After extensive controls for maternal education,
      family structure, and other household characteristics, black and Hispanic
      children have later bedtimes than white children and reduced odds of using
      regular bedtimes (by 22% and 29%, respectively) and using bedtime routines (by
      47% and 33%, respectively). Low maternal education, increased household size, and
      poverty are associated with decreased use of parent-child interactive and hygiene
      related bedtime routines. CONCLUSION: Children from disadvantaged households are
      less likely to have consistent bedtime routines than their more advantaged
      counterparts. This may contribute to later disparities in sleep quality, duration
      and timing, factors known to be associated with adverse behavioral, cognitive,
      and health outcomes.

PMID- 19745761
TI  - Pediatric gastroesophageal reflux clinical practice guidelines: joint
      recommendations of the North American Society for Pediatric Gastroenterology,
      Hepatology, and Nutrition (NASPGHAN) and the European Society for Pediatric
      Gastroenterology, Hepatology, and Nutrition (ESPGHAN).
AB  - OBJECTIVE: To develop a North American Society for Pediatric Gastroenterology,
      Hepatology, and Nutrition (NASPGHAN) and European Society for Pediatric
      Gastroenterology, Hepatology, and Nutrition (ESPGHAN) international consensus on
      the diagnosis and management of gastroesophageal reflux and gastroesophageal
      reflux disease in the pediatric population. METHODS: An international panel of 9
      pediatric gastroenterologists and 2 epidemiologists were selected by both
      societies, which developed these guidelines based on the Delphi principle.
      Statements were based on systematic literature searches using the best-available
      evidence from PubMed, Cumulative Index to Nursing and Allied Health Literature,
      and bibliographies. The committee convened in face-to-face meetings 3 times.
      Consensus was achieved for all recommendations through nominal group technique, a
      structured, quantitative method. Articles were evaluated using the Oxford Centre
      for Evidence-based Medicine Levels of Evidence. Using the Oxford Grades of
      Recommendation, the quality of evidence of each of the recommendations made by
      the committee was determined and is summarized in appendices. RESULTS: More than
      600 articles were reviewed for this work. The document provides evidence-based
      guidelines for the diagnosis and management of gastroesophageal reflux and
      gastroesophageal reflux disease in the pediatric population. CONCLUSIONS: This
      document is intended to be used in daily practice for the development of future
      clinical practice guidelines and as a basis for clinical trials.

PMID- 19745762
TI  - Gangliosides protect bowel in an infant model of necrotizing enterocolitis by
      suppressing proinflammatory signals.
AB  - OBJECTIVES: Necrotizing enterocolitis (NEC) has high morbidity in premature
      infants. Hypoxia-ischemia, infection, and enteral feeding are risk factors
      associated with NEC, whereas feeding human milk is protective. Vasoactive and
      inflammatory mediators in NEC remain elusive. Gangliosides are found in human
      milk and enterocyte membranes. An infant bowel model of NEC was developed to test
      the hypothesis that gangliosides modulate the inflammatory response to infection
      and hypoxia. PATIENTS AND METHODS: Viable, noninflamed bowel was obtained from 9
      infants between 26 and 40 weeks' gestational age. Infant bowel was treated in
      culture with Escherichia coli lipopolysaccharide (LPS) and hypoxia in the
      presence or absence of preexposure to gangliosides. Bowel necrosis and production
      of nitric oxide, endothelin-1, serotonin, eicosanoids, hydrogen peroxide, and
      proinflammatory cytokines were measured. RESULTS: Ganglioside preexposure reduced
      bowel necrosis and endothelin-1 production in response to LPS. Gangliosides
      suppressed infant bowel production of nitric oxide, leukotriene B4, prostaglandin
      E2, hydrogen peroxide, interleukin-1beta, interleukin-6, and interleukin-8 in
      response to LPS exposure and hypoxia. CONCLUSIONS: A bowel protective effect of
      gangliosides is indicated by modulation of vasoactive mediators and
      proinflammatory signal suppression.

PMID- 19745763
TI  - Use of adjuvant chemotherapy in non-small cell lung cancer in routine practice.
AB  - BACKGROUND: For many years, surgery has been the standard treatment for patients
      with early-stage non-small cell lung cancer (NSCLC). Recent randomized trials
      demonstrated that cisplatin-based adjuvant chemotherapy increases overall
      survival. The aim of this study was to analyze the precise use of adjuvant
      chemotherapy in patients with resected NSCLC in routine practice. PATIENTS AND
      METHODS: Between January 2004 and May 2005, we retrospectively analyzed 219
      patients with early-stage NSCLC who had undergone surgery at one major surgical
      center in Paris, Institut Mutualiste Montsouris. Patient characteristics, the
      type of surgery, and indications for adjuvant chemotherapy were analyzed.
      RESULTS: Eighty-seven of the 219 patients (40%) in this study had been treated
      with adjuvant chemotherapy. Different factors were associated with doctors not
      prescribing this treatment: age, comorbidity, tumor, node, metastasis stage, and
      postoperative complications. More than eight different cisplatin-based regimens
      were used, highlighting considerable heterogeneity in the use of adjuvant
      chemotherapy in daily practice. There is an increase of adjuvant chemotherapy
      during the study period. CONCLUSION: Cisplatin-based chemotherapy is the standard
      treatment for patients with resected stage II and IIIA NSCLC. However, such
      therapy is used quite heterogeneously in daily practice and specific regimens,
      and the percentage of patients receiving adjuvant chemotherapy vary from standard
      recommendations. A prospective follow-up of daily practice regarding the use of
      adjuvant chemotherapy is warranted.

PMID- 19745764
TI  - Characterization of pneumonitis in patients with advanced non-small cell lung
      cancer treated with everolimus (RAD001).
AB  - PURPOSE: To assess the incidence and radiographic and clinical presentation of
      pneumonitis associated with the mammalian target of rapamycin inhibitor
      everolimus in patients with advanced non-small cell lung cancer. PATIENTS AND
      METHODS: A retrospective, centralized review of serial computed tomography scans
      and corresponding clinical data from patients with advanced non-small cell lung
      cancer treated with 10-mg oral once daily everolimus monotherapy in a phase II
      clinical study was conducted. Serial chest CT scans underwent a consensus read by
      two radiologists for presence of pneumonitis. These cases were then reviewed with
      corresponding clinical data by a pulmonologist to assess the suspected causality
      to everolimus and outcome. RESULTS: Twenty-four of 64 patients reviewed were
      found to have radiographic evidence of pneumonitis. In 16 of these 24 patients,
      pneumonitis was suspected as either possibly (12) or probably (4) related to
      everolimus. The most common radiographic manifestations were focal areas of
      consolidation at the lung bases or ground-glass opacities. Pneumonitis evaluated
      with Common Terminology Criteria for Adverse Events (version 3) was grade 1 or 2
      in 12 of 16 suspected cases, with 4 patients experiencing higher grades. In most
      of the patients, pneumonitis remained at the same or lower grade without
      discontinuation of therapy. Patients with evidence of interstitial lung disease
      at baseline had an increased risk of Common Terminology Criteria for Adverse
      Events grade more than or equal to 3 pneumonitis. CONCLUSION: Within the
      limitation of this retrospective study, results suggest that a mostly low-grade
      pneumonitis with a possible or probable relationship to everolimus was relatively
      frequent, occurring in 25% of evaluated patients. These results suggest a need
      for monitoring of pulmonary adverse events and the development of guidelines for
      managing pneumonitis in future studies with everolimus.

PMID- 19745765
TI  - Safety, pharmacokinetics, and pharmacodynamics of the insulin-like growth factor
      type 1 receptor inhibitor figitumumab (CP-751,871) in combination with paclitaxel
      and carboplatin.
AB  - INTRODUCTION: This phase 1 study was conducted to determine the recommended phase
      2 dose of the selective insulin-like growth factor type 1 receptor (IGF-IR)
      inhibitor figitumumab (F, CP-751,871) given in combination with paclitaxel and
      carboplatin in patients with advanced solid tumors. METHODS: Patients received
      paclitaxel 200 mg/m2, carboplatin (area under the curve of 6), and F (0.05-20
      mg/kg) q3 weeks for up to six cycles. Patients with objective response or stable
      disease were eligible to receive additional cycles of single agent F until
      disease progression. Safety, efficacy, pharmacokinetic, and pharmacodynamic
      endpoints were investigated. RESULTS: Forty-two patients, including 35 with
      stages IIIB and IV non-small cell lung cancer (NSCLC), were enrolled in eight
      dose escalation cohorts. A maximum tolerated dose was not identified. Severe
      adverse events possibly related to F included fatigue, diarrhea, hyperglycemia,
      gamma glutamyl transpeptidase elevation, and thrombocytopenia (one case each). F
      plasma exposure parameters increased with dose. Fifteen objective responses
      (RECIST) were reported, including two complete responses in NSCLC and ovarian
      carcinoma. Notably, levels of bioactive IGF-1 seemed to influence response to
      treatment with objective responses in patients with a high baseline-free IGF-1 to
      IGF binding protein-3 ratio seen only in the 10 and 20 mg/kg dosing cohorts.
      CONCLUSIONS: F was well tolerated in combination with paclitaxel and carboplatin.
      Based on its favorable safety, pharmacokinetic, and pharmacodynamic properties,
      the maximal feasible dose of 20 mg/kg has been selected for further
      investigation.

PMID- 19745766
TI  - Differences in the expression profiles of excision repair crosscomplementation
      group 1, x-ray repair crosscomplementation group 1, and betaIII-tubulin between
      primary non-small cell lung cancer and metastatic lymph nodes and the
      significance in mid-term survival.
AB  - INTRODUCTION: This study aimed to compare the expression profiles of excision
      repair crosscomplementation group 1 (ERCC1), x-ray repair crosscomplementation
      group 1 (XRCC1), and betaIII-tubulin between patients with primary non-small cell
      lung cancer (NSCLC) and those with metastatic lymph nodes and to identify the
      prognostic significance of each chemotherapy resistance protein. MATERIALS: Those
      who met the inclusion criteria were patients (1) with NSCLC, (2) with metastatic
      lymph nodes (N1 or N2), and (3) who underwent surgical resection followed by
      platinum-based adjuvant chemotherapy. A total of 82 patients were included in the
      study. The expression profile of each protein was evaluated by
      immunohistochemistry and compared according to tumor location. RESULTS: The mean
      age of the patients was 57.5 +/- 8.4 years. There were 30 N1 and 52 N2 patients.
      ERCC1 expression was upregulated in 55% and downregulated in 8% of metastatic
      lymph nodes, when compared with primary tumors (p < 0.05). XRCC1 was also
      upregulated in 56% and downregulated in 6% (p < 0.05). However, betaIII-tubulin
      was upregulated in 12% and downregulated in 45% of patients (p < 0.05). betaIII
      tubulin expression in metastatic lymph nodes was greater in patients with
      adenocarcinoma than other cell types. Upregulation of ERCC1 in metastatic lymph
      nodes was a poor prognostic factor in N1 patients but not in N2 patients.
      CONCLUSIONS: Significant changes in the expression profile of each protein were
      observed in metastatic lymph nodes. The resistance protein-guided treatment
      should be performed after integrative interpretation of expression profiles of
      each protein in both primary and metastatic sites.

PMID- 19745767
TI  - Hemithoracic radiotherapy after extrapleural pneumonectomy for malignant pleural
      mesothelioma: a dosimetric comparison of two well-described techniques.
AB  - INTRODUCTION: Extrapleural pneumonectomy (EPP) with adjuvant radiotherapy may be
      used to treat malignant pleural mesothelioma. Radiation pneumonitis, felt to be
      related to contralateral lung radiation dose, may affect patient mortality in
      this setting. Two standard therapeutic approaches currently used to deliver
      adjuvant radiotherapy were compared in this study: intensity modulation radiation
      treatment (IMRT) with a planned dose of 45 Gray (Gy) and a modified electron
      photon technique delivering 54 Gy. METHODS: Treatment plans of 10 mesothelioma
      patients who underwent EPP and hemithoracic IMRT to a total dose of 45 Gy were
      analyzed. Plans using a combination of opposed anterior posterior radiation
      fields and electron supplementation (electron-photon technique [EPT]) to a total
      dose of 54 Gy were then generated and compared with IMRT plans. RESULTS:
      Dosimetric comparison revealed a significant reduction in contralateral lung dose
      with EPT versus IMRT, even with increased prescription dose used with EPT plans.
      Median heart and contralateral kidney doses were also significantly reduced with
      EPT versus IMRT. Dose coverage of planning target volume and doses to spinal
      cord, liver, and ipsilateral kidney were similar with use of the two techniques.
      CONCLUSIONS: Our data suggest that hemithoracic radiotherapy delivered after EPP
      using EPT may minimize dose to contralateral lung and other structures when
      compared with IMRT, without compromise of planning target volume coverage.

PMID- 19745768
TI  - Is pneumonectomy after induction chemotherapy for non-small cell lung cancer a
      reasonable procedure? A multicenter retrospective study of 228 cases.
AB  - INTRODUCTION: Pneumonectomy (PN) after induction chemotherapy (CT) for non-small
      cell lung cancer is controversial because high-mortality rates are still
      reported. METHODS: This multicenter retrospective study included all patients
      treated by induction CT then PN between January 1993 and April 2006 in four
      General and Thoracic Surgery Departments. Postoperative mortality and morbidity
      and long-term outcomes were studied. RESULTS: The study considered 228 patients.
      Doublets with cisplatin and vinorelbine or gemcitabine were used in 66% of cases.
      pTNM stages (World Health Organization, 1997) were 0 (2%), I (16%), II (25%),
      IIIA (29%), IIIB (16%), and IV (12%). The postoperative morbidity rate was 37%
      (84 of 228 patients). The independent risk factors identified for postoperative
      morbidity were chronic obstructive pulmonary disease, more than four cycles of
      induction CT or an association of cisplatin, and an old cytotoxic molecule,
      extended PN, and extended anesthesia time. Postoperative mortality rates were
      5.3% at 30 days (12 of 228 patients) and 9.2% at 90 days (21 of 228 patients).
      The independent risk factors identified for operative mortality were chronic
      obstructive pulmonary disease, manual suture of the stump, and pTNM stage higher
      than IIIA. The 90-day mortality rates were 10.3% (12 of 117) for right PN and
      8.2% (9 of 111) for left PN (p = 0.65). The overall survival (OS) rates were 68%
      at 1 year, 39% at 3 years, and 32% at 5 years. CONCLUSIONS: Induction CT was not
      found to compromise short- or long-term outcomes after PN in non-small cell lung
      cancer. The right or left PN performed by experienced surgeons after induction CT
      seems to be a reasonable procedure in case of tumor local extension.

PMID- 19745769
TI  - Stage III thymic epithelial neoplasms are not homogeneous with regard to
      clinical, pathological, and prognostic features.
AB  - INTRODUCTION: The main therapeutic approach to a Masaoka stage III thymic
      epithelial neoplasm (TEN) is surgical resection, and the 5-year survival rate is
      approximately 60%. According to the Masaoka staging system, invasion of
      neighboring organs is classified as stage III disease, regardless of the number
      of organs involved or the size of the tumor. We retrospectively analyzed the
      prognostic significance associated with the extent of disease in patients with
      Masaoka stage III TENs. METHODS: From 1995 to 2006, 241 patients were identified
      with thymomas. Among these patients, 59 were diagnosed with Masaoka stage III
      disease. The patients with a stage III TEN were advised to have extended
      thymectomy with en bloc resection of the invaded structures as the initial
      treatment. The prognostic significance of the size, organs invaded, and other
      factors were analyzed. RESULTS: The overall survival rates for the stage III
      patients were 83% and 64%, and the recurrence-free survival rates were 56% and
      51%, at 5 and 8 years, respectively. Patients with a low-grade World Health
      Organization classification (p = 0.0202) or a complete resection (p < 0.0001) had
      a better overall survival. In addition, patients with tumors less than 6.5 cm (p
      = 0.0311) or with pericardium invasion (p = 0.0299) had a better recurrence-free
      survival. The patients with limited disease had a better prognosis for a
      recurrence-free survival than did patients with extensive disease (p = 0.0007).
      CONCLUSIONS: Heterogeneous prognostic subgroups based on tumor size and organs
      invaded were identified in patients with Masaoka stage III TENs. Therapeutic
      plans, based on these subgroups, will potentially improve patient management and
      treatment outcomes.

PMID- 19745770
TI  - Carinal resection and reconstruction in surgical treatment of bronchogenic
      carcinoma with carinal involvement.
AB  - BACKGROUND: Carinal resection and reconstruction is technically demanding. The
      aim of this study is to discuss the clinical value of carinoplasty in the
      surgical treatment of bronchogenic carcinoma involving carina. MATERIALS AND
      METHODS: From 1982 to 2006, 41 cases of centrally placed bronchogenic carcinoma
      invading the carina were treated with carinal resection and reconstruction in our
      hospital. Among the 41 patients, 25 patients simultaneously underwent additional
      cardiovascular plasty operations besides carinoplasty. There were 12 different
      types of carinal resection and reconstruction in our group. RESULTS: In this
      group, there was one perioperative death due to anastomotic leakage. This patient
      died 2 weeks postoperatively. Arrhythmia occurred in 12 patients, atelectasis in
      eight patients, and pneumonia in five patients. Five patients had to be assisted
      with mechanical ventilation because of pulmonary function failure. Anastomosis
      stenoses were found in three patients 3 to 6 months postoperatively and were
      resolved by stent insertion. Thirty-one patients were diagnosed with tumor
      recurrences after operations. Progression-free survival was 75.6% at 1 year,
      43.9% at 3 years, and 22.0% at 5 years; the overall actuarial survival was 75.6%
      at 1 year, 46.3% at 3 years, and 26.8% at 5 years. Survival was better in
      patients with N0-1 disease than those with N2 disease (37.0% versus 7.1% at 5
      years). CONCLUSION: Carinoplasty for bronchogenic carcinoma involving carina is
      feasible with acceptable morbidity and mortality if patients are selected
      carefully. Preoperative evaluation of the mediastinum is crucial for treatment
      selection.

PMID- 19745771
TI  - A tissue selective estrogen complex: a new horizon for menopausal symptoms.

PMID- 19745772
TI  - Hyperinsulinemia in nonobese women reporting a moderate weight gain at the
      beginning of menopause: a useful early measure of susceptibility to insulin
      resistance.
AB  - OBJECTIVE: At menopause, the frequent weight gain excess could be related to
      insulin resistance. This study evaluated the prevalence of hyperinsulinemia in
      nonobese women reporting a moderate increase in weight at the beginning of
      menopause. METHODS: Women who were postmenopausal for 1 to 5 years and reporting
      a weight gain of 5 to 15 kg were evaluated for weight, eating habits, physical
      activity, body circumferences, fasting blood glucose level, insulin level, and
      lipid profile. An oral glucose tolerance test was performed in subgroups of 21
      hyperinsulinemic women and 21 normoinsulinemic women matched for age, weight,
      height, body mass index, and hysterectomy. RESULTS: Among 279 postmenopausal
      women reporting a weight gain of 8.7 +/- 4.4 kg, insulin level was increased in
      49 (17.6%) women as compared with normoinsulinemic women (108.53 +/- 31.35 vs
      58.96 +/- 14.52 pmol/L, respectively; P < 0.001). Differences were also found for
      glucose (5.24 +/- 0.37 vs 5.05 +/- 0.42 mmol/L, respectively; P = 0.003), insulin
      resistance as estimated by homeostasis model assessment HOMA-2-IR (2.01 +/- 0.53
      vs 1.10 +/- 0.27, respectively; P < 0.001), weight (72.6 +/- 8.0 vs 69.9 +/- 7.1
      kg, respectively; P = 0.023), body mass index (28.3 +/- 2.3 vs 27.2 +/- 2.3
      kg/m2, respectively; P = 0.003), and waist circumference (89.8 +/- 5.8 vs 86.0 +/
      6.5 cm, respectively; P < 0.001). Triglyceride levels were higher (1.47 +/- 0.66
      vs 1.17 +/- 0.61 mmol/L, respectively; P = 0.002) and high-density lipoprotein
      cholesterol level was lower (1.54 +/- 0.35 vs 1.72 +/- 0.42 mmol/L, respectively;
      P = 0.007) in the hyperinsulinemic and normoinsulinemic groups. Although insulin
      levels were higher in 21 hyperinsulinemic women at all times that oral glucose
      tolerance tests were performed, levels of glucose were also above those of 21
      matched normoinsulinemic women at 1 and 2 hours and remained greater than 6.0
      mmol/L at 2 hours. CONCLUSIONS: Because insulin resistance is frequently
      associated with weight gain in nonobese women at menopause, the measurement of
      fasting insulin, along with glucose, lipids, and waist circumference, may help to
      identify those who are at higher risk of developing glucose intolerance,
      metabolic syndrome, diabetes, and cardiovascular diseases and to implement early
      preventive measures.

PMID- 19745773
TI  - Cardioprotective effects of long-term treatment with raloxifene, a selective
      estrogen receptor modulator, on myocardial ischemia/reperfusion injury in
      ovariectomized rats.
AB  - OBJECTIVE: The aim of this study was to investigate the beneficial effect of long
      term treatment with raloxifene (RAL), a selective estrogen receptor modulator, on
      myocardial ischemia/reperfusion (MI/R) injury in ovariectomized (Ovx) rats.
      METHODS: Ovariectomy was performed in female Sprague-Dawley rats 8 weeks old. Ovx
      rats were treated with RAL 1 or 5 mg/kg (gavage, once daily) or 17beta-estradiol
      (E2; 50 microg/kg SC, three times a week) for 8 weeks. The cardioprotective
      effect of RAL was evaluated in an open-chest anesthetized rat model of MI/R,
      which was induced by 40-minute left coronary artery occlusion and 100-minute
      reperfusion. RESULTS: Long-term treatment with RAL 1 mg/kg significantly
      suppressed the duration of ventricular tachycardia elicited by MI. After MI/R,
      the levels of plasma creatine kinase-MB fraction and lactate dehydrogenase in Ovx
      rats were significantly higher than those in the sham group, which were
      significantly reduced by long-term treatment with RAL 1 mg/kg or E2. Neutrophil
      myeloperoxidase activity in ischemic myocardium markedly increased in the Ovx
      group, whereas long-term treatment with RAL 1 or 5 mg/kg or E2 significantly
      suppressed the elevation of myeloperoxidase activity. After MI/R, the protein
      expression of phosphorylated inhibitory kappaBalpha and caspase-3 in ischemic
      myocardium pronouncedly increased in the Ovx group and was attenuated by long
      term treatment with RAL 1 mg/kg or E2. CONCLUSIONS: Long-term treatment with RAL
      can reduce the severity of MI-induced arrhythmias and attenuate MI/R-induced
      damages and apoptosis in Ovx rats. This cardioprotective effect of RAL may be
      associated with inhibition of neutrophil infiltration and suppression of nuclear
      factor-kappaB activation.

PMID- 19745774
TI  - Japanese clinical guidelines for autoimmune pancreatitis.
AB  - OBJECTIVES: As the patients with autoimmune pancreatitis (AIP) are increasing in
      Japan, the practical guideline for managing AIP is required to be established.
      METHODS: Three committees (the professional committee for making clinical
      questions [CQs] and statements by Japanese specialists, the expert panelist
      committee for rating statements by the modified Delphi method, and the evaluating
      committee by moderators) were organized. Fifteen specialists for AIP extracted
      the specific clinical statements from a total of 871 literatures by PubMed search
      (approximately 1963-2008) and from a secondary database and made the CQs and
      statements. The expert panelists individually rated these clinical statements
      using a modified Delphi approach, in which a clinical statement receiving a
      median score greater than 7 on a 9-point scale from the panel was regarded as
      valid. RESULTS: The professional committee made 13, 6, 6, and 11 CQs and
      statements for the concept and diagnosis, extrapancreatic lesions, differential
      diagnosis, and treatment, respectively. The expert panelists regarded them as
      valid after a 2-round modified Delphi approach. CONCLUSIONS: After evaluation by
      the moderators, the Japanese clinical guideline for AIP has been established.
      Further studies for the international guideline are needed after international
      consensus for diagnosis and treatment.

PMID- 19745775
TI  - Pancreatic adenocarcinoma tumor grade determination using contrast-enhanced
      magnetic resonance imaging.
AB  - OBJECTIVES: To determine whether the degree of enhancement of pancreatic
      adenocarcinoma visualized on arterial phase gadolinium-enhanced magnetic
      resonance imaging (MRI) correlates with the histopathological tumor grade.
      METHODS: Thirty-nine patients with pancreatic adenocarcinoma had MRI within 14
      days before tumor resection. Gadolinium-chelate-enhanced (Gd) 3-dimensional
      gradient echo images were acquired including the arterial phase. Tumor imaging
      patterns on the arterial phase images were classified for low, moderate, or high
      degree of enhancement and compared against conventional histological grading.
      RESULTS: Based on histological grading, there were 12 poorly differentiated, 2
      poorly to moderately differentiated, 22 moderately differentiated, and 3 well
      differentiated adenocarcinomas. There was agreement between the MRI arterial
      enhancement pattern and histological grading in 30 of 39 cases. The mean size of
      tumors grouped by enhancement pattern or grade was not significantly different
      between groups. Although minor discordance was found in 9 of the 39 cases,
      statistical analysis showed agreement between the degree of arterial enhancement
      on MRI and histological tumor differentiation; the Cohen's kappa value was 0.64
      with a 95% confidence interval of 0.46-0.83. CONCLUSIONS: Pancreatic
      adenocarcinoma arterial phase enhancement correlates with the histological grade
      of differentiation.

PMID- 19745776
TI  - Significance of renal rim grade on computed tomography in severity evaluation of
      acute pancreatitis.
AB  - OBJECTIVES: Multifactor scoring systems, such as the Acute Physiology and Chronic
      Health Evaluation (APACHE) II, are useful for predicting the severity of acute
      pancreatitis (AP); however, they are rather complicated. The aim of this study
      was to introduce renal rim grade (RRG) as a severity assessment measure for AP.
      METHODS: One hundred twenty-two eligible AP patients who underwent abdominal
      computed tomography (CT) on admission were evaluated for RRG (grades 1-3). The
      end points were the severity of illness and hospital mortality. Furthermore, RRG
      was compared with the Balthazar score, the CT severity index, the Ranson score,
      and the Acute Physiology and Chronic Health Evaluation (APACHE) II score, using a
      receiver operating characteristic analysis. RESULTS: The exacerbation rates into
      severe disease were 3% (grade 1), 48% (grade 2), and 89% (grade 3). The mortality
      rates were 3% (grade 1), 8% (grade 2), and 31% (grade 3). The area under the
      receiver operating characteristic curves to predict the severe disease and
      mortality using the RRG system were comparable with other scoring systems.
      CONCLUSIONS: Renal rim grade is useful for the evaluation of the severity of AP.

PMID- 19745777
TI  - Pancreatic ductal adenocarcinomas in long-term follow-up patients with branch
      duct intraductal papillary mucinous neoplasms.
AB  - OBJECTIVE: Although branch duct intraductal papillary mucinous neoplasms (BD
      IPMNs) are slow-growing tumors with a favorable prognosis, the synchronous
      occurrence of pancreatic ductal adenocarcinomas (PDAs) in patients with BD-IPMNs
      has been reported. This study was aimed to elucidate the development of PDAs in
      long-term follow-up patients with BD-IPMNs. METHODS: We investigated 89 BD-IPMN
      patients who had no mural nodules and followed them up conservatively at least 2
      years (median follow-up, 64 months; range, 25-158 months). All subjects underwent
      examinations by imaging modalities including endoscopic retrograde
      pancreatography. We calculated the standardized incidence ratio (SIR) from the
      vital statistics compiled by the Ministry of Health, Labor, and Welfare of Japan.
      RESULTS: Among the 89 patients, 4 cases of PDAs distant from BD-IPMN were
      observed in 552 patient-years of follow-up (7.2 per 1000 patient-years). The
      expected number was 0.25, and the SIR of PDAs was 15.8 (95% confidence interval
      [CI], 4.3-40.4; P = 0.00014). Subgroup analyses showed that the incidence of PDAs
      was significantly increased in patients 70 years or older (SIR 16.7; 95% CI, 3.4
      48.7; P = 0.0008) and in women (SIR 22.5; 95% CI, 2.7-81.1; P = 0.0037).
      CONCLUSIONS: Patients with BD-IPMNs are at a high risk for PDAs. During the
      follow-up, careful examination is required to detect the development of PDAs in
      patients with BD-IPMNs.

PMID- 19745778
TI  - Correlation of pancreatic histopathologic findings and islet yield in children
      with chronic pancreatitis undergoing total pancreatectomy and islet
      autotransplantation.
AB  - OBJECTIVES: The probability of insulin independence after intraportal islet
      autotransplantation (IAT) for chronic pancreatitis (CP) treated by total
      pancreatectomy (TP) relates to the number of islets isolated from the excised
      pancreas. Our goal was to correlate the islet yield with the histopathologic
      findings and the clinical parameters in pediatric (age, <19 years) CP patients
      undergoing TP-IAT. METHODS: Eighteen pediatric CP patients aged 5 to 18 years
      (median, 15.6 years) who underwent TP-IAT were studied. Demographics and clinical
      history came from medical records. Histopathologic specimens from the pancreas
      were evaluated for presence and severity of fibrosis, acinar cell atrophy,
      inflammation, and nesidioblastosis by a surgical pathologist blinded to clinical
      information. RESULTS: Fibrosis and acinar atrophy negatively correlated with
      islet yield (P = 0.02, r = -0.50), particularly in hereditary CP (P = 0.01).
      Previous duct drainage surgeries also had a strong negative correlation (P =
      0.01). Islet yield was better in younger (preteen) children (P = 0.02, r = -0.61)
      and in those with pancreatitis of shorter duration (P = 0.04, r = -0.39).
      CONCLUSIONS: For preserving beta cell mass, it is best to perform TP-IAT early in
      the course of CP in children, and prior drainage procedures should be avoided to
      maximize the number of islets available, especially in hereditary disease.

PMID- 19745779
TI  - Bicarbonate transport by the human pancreatic ductal cell line HPAF.
AB  - OBJECTIVES: The human pancreatic duct cell line, HPAF, has been shown previously
      to secrete Cl(-) in response to Ca(2+)-mobilizing stimuli. Our aim was to assess
      the capacity of HPAF cells to transport and secrete HCO3(-). METHODS: HPAF cells
      were grown as confluent monolayers on permeable supports. Short-circuit current
      was measured by voltage clamp. Intracellular pH (pHi) was measured by
      microfluorometry in cells loaded with 2',7'-bis(2-carboxyethyl)-5(6)
      carboxyfluorescein (BCECF). RESULTS: In HCO3(-)-free solutions, ATP-evoked
      changes in short-circuit current were inhibited by bumetanide, and the recovery
      of pHi from acid loading was abolished by 5-(N-ethyl-N-isopropyl)-amiloride
      (EIPA). In the presence of HCO3(-), ATP-evoked secretion was no longer inhibited
      by bumetanide, and there was a strong EIPA-insensitive recovery from acid
      loading, which was inhibited by 4,4'-diisothiocyanatodihydrostilbene-2,2'
      disulfonate (H2DIDS). ATP, but not forskolin, stimulated HCO3(-) efflux from the
      cells. CONCLUSIONS: In the absence of HCO3(-), ATP-evoked Cl(-) secretion is
      driven by a basolateral Na(+)-K(+)-2Cl(-) cotransporter, and pH(i) is regulated
      by apical and basolateral Na(+)/H(+) exchangers. In the presence of HCO3(-), ATP
      evoked secretion is sustained in the absence of Na(+)-K(+)-2Cl(-) cotransporter
      activity and is probably driven by basolateral Na(+)-HCO3(-) cotransport.

PMID- 19745781
TI  - Mesenchymal stem-cell transplantation for hypoxic-ischemic brain injury in
      neonatal rat model.
AB  - Neonatal hypoxic-ischemic brain injury (HIE) remains a major cause of neurologic
      disabilities. However, many experimental therapies have shown limited successes.
      We assessed whether human mesenchymal stem cells (MSCs) could be transplanted in
      the HIE rat brain to improve neurologic disabilities. P7 SD rats were either
      subjected to left carotid artery ligation and hypoxic exposure [hypoxia-ischemia
      (HI)] or sham operation and normoxic exposure (sham). On P10, rat pubs received
      either PKH26-labeled MSCs or buffer via intracardial injection, resulting in four
      experimental groups: sham-buffer, sham-MSC, HI-buffer, and HI-MSC. Cylinder test
      and accelerating rotarod test were performed 14, 20, 30, and 40 d after
      injection. Six weeks after injection, cresyl violet and double immunofluorescence
      staining were performed. MSCs were transplanted to the whole brain mainly after
      HI. Glial fibrillary acidic protein and OX42 were more abundantly colocalized
      with MSC than neuronal specific nuclear protein or myelin basic protein. There
      were no significant differences in the total amounts and cell types between the
      lesioned and nonlesioned hemisphere. The lesioned hemispheric volume was
      decreased after HI (p = 0.012) but not restored by MSC. Neurologic performance
      was significantly impaired only on the cylinder test after HI (p = 0.034), and
      MSC transplants improved it (p = 0.010). These suggest MSC can be a candidate for
      the treatment of neonatal HIE.

PMID- 19745780
TI  - Microbiologic and histologic characteristics of the extremely preterm infant's
      placenta predict white matter damage and later cerebral palsy. the ELGAN study.
AB  - Inflammatory phenomena seem to contribute to the occurrence of perinatal cerebral
      white matter damage and CP. The stimulus that initiates the inflammation remains
      obscure. One thousand two hundred forty-six infants born before the 28th
      postmenstrual week had a protocol ultrasound scan of the brain read concordantly
      by two independent sonologists. Eight hundred ninety-nine of the children had a
      neurologic examination at approximately 24-mo postterm equivalent. The placenta
      of each child had been biopsied under sterile conditions and later cultured.
      Histologic slides of the placenta were examined specifically for this study.
      Recovery of a single microorganism predicted an echolucent lesion, whereas
      polymicrobial cultures and recovery of skin flora predicted both ventriculomegaly
      and an echolucent lesion. Diparetic CP was predicted by recovery of a single
      microorganism, multiple organisms, and skin flora. Histologic inflammation
      predicted ventriculomegaly and diparetic CP. The risk of ventriculomegaly
      associated with organism recovery was heightened when accompanied by histologic
      inflammation, but the risk of diparetic CP was not. Low-virulence microorganisms
      isolated from the placenta, including common skin microflora, predict ultrasound
      lesions of the brain and diparetic CP in the very preterm infant. Organism
      recovery does not seem to be needed for placenta inflammation to predict
      diparetic CP.

PMID- 19745782
TI  - Electrographic seizures in preterm infants during the first week of life are
      associated with cerebral injury.
AB  - The aim of the study was to determine the incidence of electrographic seizure
      activity in a prospective cohort of preterm infants and relate it to the presence
      of cerebral injury. Infants born <30-wk gestation received a median 74 h of
      continuous 2-channel EEG with amplitude-integrated EEG monitoring in the first
      week of life. Infants were classified in the abnormal outcome group if they died
      in the neonatal period and/or had grades 3-4 intraventricular hemorrhage and/or
      moderate or severe abnormalities on cerebral MRI. Seizures were defined as
      rhythmic spike and/or wave activity lasting at least 10 s on the raw EEG trace.
      Eleven of 51 infants monitored had electrographic seizures. These infants were
      more premature had lower birth weights and a greater proportion had abnormal
      outcomes. In four infants, seizures preceded ultrasound findings of grades 3-4
      intraventricular hemorrhage. Three of the four infants with seizures and
      concurrent physiologic recordings displayed concurrent rises in heart rate and
      one showed a fall in respiratory rate. In conclusion, electrographic seizures
      were more likely to occur in the sicker and more premature infants with abnormal
      outcomes. Seizures detected on continuous amplitude-integrated EEG monitoring
      with the raw EEG were associated with poor outcome.

PMID- 19745783
TI  - Exposure to supplemental oxygen and its effects on oxidative stress and
      antioxidant enzyme activity in term newborn lambs.
AB  - The optimal oxygen concentration for the resuscitation of term infants remains
      controversial. We studied the effects of 21 versus 100% oxygen immediately after
      birth, and also exposure for 24 h to 100% oxygen, on oxidant lung injury and lung
      antioxidant enzyme (AOE) activities in term newborn lambs. Lambs at 139 d
      gestation were delivered and ventilated with 21% (RAR) or 100% (OXR) for 30 min.
      A third group of newborn lambs were ventilated with 100% O2 for 24 h (OX24).
      Oxidized glutathione levels in whole blood were significantly different among the
      groups with lower values in the RAR group, and these values correlated highly
      with partial pressure of arterial oxygen (Pao2). The reduced to oxidized
      glutathione ratio was significantly different among the groups, the ratio
      decreasing with increasing oxygen exposure. Lipid hydroperoxide (LPO) activity
      was significantly higher in the OXR and OX24 groups. AOE activity was higher in
      the whole lung and in red cell lysate in the OX24 group. Increased
      myeloperoxidase (MPO) activity, percent neutrophils, and proteins in lung lavage
      suggested inflammation in the OX24 group after maximal oxygen exposure. We
      conclude that even relatively brief exposure of the lung to 100% oxygen increases
      systemic oxidative stress and lung oxidant injury in ventilated term newborn
      lambs.

PMID- 19745784
TI  - Overexpression of allograft inflammatory factor-1 promotes the proliferation and
      migration of human endothelial cells (HUV-EC-C) probably by up-regulation of
      basic fibroblast growth factor.
AB  - Our previous study demonstrated that allograft inflammatory factor-1 (AIF-1) is
      present in the vessels of infantile hemangiomas but neither in the vessels of
      vascular malformations, pyogenic granulomas, normal skin, placental tissues nor
      in the neovessels of squamous cell carcinomas of the tongue. The purpose of this
      study was to explore the impact of AIF-1 alterations on endothelial cells (EC).
      Stable introduction of AIF-1 to the human umbilical vein EC line (HUV-EC-C) in
      vitro revealed that AIF-1 enhances the proliferation and migration of the EC and
      promotes G0/G1-to-S-phase transition, accompanied by up-regulation of basic
      fibroblast growth factor (p < 0.05). In contrast, AIF-1 did not affect the
      expression of granulocyte colony-stimulating factor, VEGF-a, monocyte
      chemoattractant protein-1, or tissue inhibitor of metalloproteinase-1. AIF-1
      expression was not induced by hypoxia, VEGF-a, basic fibroblast growth factor, or
      insulin-like growth factor-2 in EC. Taken together, these findings suggest that
      the impact of AIF-1 on EC would stimulate angiogenesis and consequently affect
      the progression of infantile hemangiomas.

PMID- 19745785
TI  - Neonatal dexamethasone treatment in the rat leads to kidney damage in adulthood.
AB  - Recently, concern has been raised that corticosteroid treatment of preterm
      neonates might be associated with adverse effects later in life, including early
      development of hypertension. Here, we investigate the impact of neonatal
      dexamethasone (Dex) treatment on early renal cell proliferation and nephron
      number. We analyzed mitotic activity in renal cortex of rat pups neonatally
      treated with Dex. Nephron number was measured and possible renal damage was
      quantified by counting inflammatory foci, ED-1 positive cells (macrophages), and
      the desmin score (activated podocytes). Mitotic activity was 34 and 29% lower on
      d 2 and 4 in Dex-treated rats compared with saline-treated controls. The number
      of glomeruli was lower at 4 wk, but nephron size was unchanged after Dex
      treatment, as calculated from glomerular density and (lower) body- and kidney
      weight. At wk 50, the glomerular number was significantly lower in Dex-treated
      rats, whereas body and kidney weight were the same as in Sal controls. Dex rats
      also showed more kidney damage, manifested by a approximately 3.5-fold increase
      in inflammation foci/mm and in ED-1 positive cells/mm and a approximately 4.3
      fold increased desmin score. Temporary suppression of mitotic activity during
      neonatal Dex treatment leads to reduction of nephron number and more kidney
      damage later in life. ABBREVIATIONS: :

PMID- 19745786
TI  - A pharmacogene database enhanced by the 1000 Genomes Project.
AB  - Human genetic variation is likely to be responsible for a substantial fraction of
      the variability in complex traits including drug response. Single nucleotide
      polymorphisms have been implicated in drug response using genome-wide association
      studies as well as candidate-gene approaches. A more comprehensive catalogue of
      human genetic variation should complement the current large-scale genotypic
      dataset from the International HapMap Project, which focuses on common genetic
      variants. The 1000 Genomes Project is an international research effort that aims
      to provide the most comprehensive map of human genetic variation using next
      generation sequencing platforms. Owing to the lack of convenient tools, however,
      it is a challenge for the pharmacogenetic research community to take advantage of
      these data. Here, we present a new database of some pharmacogenes of particular
      interest to pharmacogenetic researchers. Our database provides a convenient
      portal for immediate utilization of the newly released 1000 Genomes Project data
      in pharmacogenetic studies.

PMID- 19745787
TI  - Identification and characterization of novel polymorphisms in the basal promoter
      of the human transporter, MATE1.
AB  - OBJECTIVES: Human multidrug and toxin extrusion member 1, MATE1 (SLC47A1), plays
      an important role in the renal and biliary excretion of endogenous and exogenous
      organic cations including many therapeutic drugs. In this study, we characterized
      the transcriptional effects of five polymorphic variants and six common
      haplotypes in the basal promoter region of MATE1 that were identified in 272 DNA
      samples from ethnically diverse US populations. METHODS: We measured luciferase
      activities of the six common promoter haplotypes of MATE1 using in-vitro and in
      vivo reporter assays. RESULTS: Haplotypes that contain the most common variant
      (mean allele frequency in four ethnic groups: 0.322), g.-66T>C, showed a
      significant decrease in reporter activities compared to the reference. Two
      transcription factors, activating protein-1 (AP-1) and activating protein-2
      repressor (AP-2rep), were predicted to bind to the promoter in the region of g.
      66T>C. Results from electrophoretic mobility shift assays showed that the g.-66T
      allele, exhibited greater binding to AP-1 than the g.-66C allele. AP-2rep
      inhibited the binding of AP-1 to the MATE1 basal promoter region, and the effect
      was considerably greater for the g.-66T>C. These data suggest that the reduced
      transcriptional activity of g.-66T>C results from a reduction in the binding
      potency of the transcriptional activator, AP-1, and an enhanced binding potency
      of the repressor, AP-2rep to the MATE1 basal promoter region. Consistent with the
      reporter assays, MATE1 mRNA expression levels were significantly lower in kidney
      samples from individuals who were homozygous or heterozygous for g.-66T>C in
      comparison with samples from individuals who were homozygous for the g.-66T
      allele. CONCLUSION: Our study suggests that the rate of transcription of MATE1 is
      regulated by AP-1 and AP-2rep and that a common promoter variant, g.-66T>C may
      affect the expression level of MATE1 in human kidney, and ultimately result in
      variation in drug disposition and response.

PMID- 19745788
TI  - Plagiarism and dual publication: review of the issues and policy statement.

PMID- 19745789
TI  - 6-Acetylmorphine detected in the absence of morphine in pain management patients.
AB  - Liquid chromatography tandem mass spectrometry was used to identify and confirm
      the presence of 6-acetylmorphine and morphine in 22,361 urines of pain management
      patients. Thirty urines tested positive for 6-acetylmorphine above a cutoff of 10
      ng/mL. Twenty-three percent of the patients with urinary concentrations of 6
      acetylmorphine above 10 ng/mL had urinary morphine concentrations below 300
      ng/mL.

PMID- 19745791
TI  - A rapid and sensitive LC-MS/MS method for determination of fluconazole in human
      plasma and its application in infants with Candida infections.
AB  - A rapid and sensitive LC-MS/MS method was developed to quantify fluconazole in
      human plasma. Seventy microliters of plasma were treated with protein
      precipitation procedures. Chromatographic separation was achieved on a C18 column
      using a gradient mobile phase of acetonitrile and water in 0.1% formic acid.
      Fluconazole and its deuterium-labeled internal standard were monitored in
      positive mode using electrospray ionization source. The method was fully
      validated over the range of 0.01 to 10 microg/mL. Intraday and interday precision
      ranged from 2.84% to 10.8% and 5.27% to 11.5%, respectively. The process recovery
      efficiency for fluconazole ranged from 98.6% to 104.4%. No carryover and minimal
      matrix effects were observed. Acceptable stability of fluconazole in blood at
      room temperature for up to 72 hours guaranteed that fluconazole concentrations in
      scavenged blood specimens were usable for infant PK analysis and model
      development. This method has been utilized for a fluconazole pharmacokinetic
      trial with 55 preterm and term infants younger than 90 days of age. The fast
      sample preparation cycle and lower limit of quantitation make this method a
      potential tool for therapeutic drug monitoring of fluconazole to optimize
      pediatric antifungal therapy. Optimal dose regimen of fluconazole in neonates and
      young infants might be achieved with application of TDM and pharmacometric
      approach designed to achieve AUC/MIC >50 for most Candida species with a MIC90
      less than 8 microg/mL.

PMID- 19745792
TI  - Stem cells and reproductive medicine.
AB  - For decades it has remained as a central dogma in dogma in reproductive biology
      that female mammals are born with a set non-renewable number of germ cells in the
      ovary. Recent revolutionary studies challenged this dogma by showing postnatal
      oogenesis in the adult ovary. In this review article the formation of primordial
      germ cells (PGC), the precursors of adult gametocytes beginning from their
      specification to their migration to prospective gonads will be reviewed with a
      special emphasis on stem cells studies that obtained gametocytes from germ and
      non germline stem cells.

PMID- 19745793
TI  - Treatment options for impaired spermatogenesis: germ cell transplantation and
      stem-cell based therapy.
AB  - Advances in infertility treatment had the most extraordinary breakthrough with
      the birth of the first in vitro fertilization baby in 1978. Fourteen years later,
      intracytoplasmic sperm injection has been introduced for the treatment of male
      factor infertility. Intra cytoplasmic sperm injection in combination with
      testicular sperm extraction has allowed men with azoospermia to father children.
      In fact, as long as a fully developed spermatozoon is identified, it can be
      utilized or can even be duplicated to inseminate several oocytes while providing
      information on its genomic content. There are, however, men who are suffering
      from spermatogenic arrest, where no post-meiotic germ cells are retrieved, and
      therefore, unable to generate their own offspring. More recently, the successful
      isolation and cultivation of spermatogonial stem cells has allowed the
      exploration of their biological characteristics and their application in
      therapeutic approaches following transplantation or in vitro maturation. Finally,
      men diagnosed with germ cell aplasia can only be treated by donor or de novo
      generated gametes. In the past several years, we have attempted to manufacture
      gametes by inducing haploidization of somatic cells and more recently, generating
      sperm-like cells through embryonic stem cell differentiation.

PMID- 19745794
TI  - Evaluation of male infertility.
AB  - Infertility is an emotionally charged problem affecting an estimated 15% of all
      couples. The man should be evaluated concurrently with the woman, since a male
      factor is the primary or contributing cause in 40% to 60% of cases. In addition
      to detecting treatable abnormalities, evaluation of the infertile man is critical
      to uncover life-threatening problems associated with the symptom of infertility,
      as well as genetic conditions associated with male infertility that could be
      transmitted to offspring with assisted reproduction. New diagnostic tests have
      been developed and surgical techniques refined resulting in improved treatment
      results and patient care. Dramatic advancements in, and widespread use of,
      assisted reproductive techniques such as intracytoplasmic sperm injection have
      created alternatives for couples who previously had little hope of reproductive
      success. The infertility practitioner should have a thorough understanding of the
      advantages and limitations of various laboratory tests as well as the
      indications, costs and success rates of all treatment options. The first step in
      evaluation is a thorough history and physical examination with initiation of
      basic laboratory studies.

PMID- 19745795
TI  - Endometriosis: a critical appraisal of the advances and the controversies of a
      challenging health problem.
AB  - Endometriosis is an enigmatic disorder with obscure pathogenesis. The objective
      of this review was to critically appraise the recent advances in the
      etiopathogenesis, diagnosis and clinical management of endometriosis. Several
      studies support the familial role in the initiation of the disease with key roles
      of endometriosis-associated polymorphisms in the genes that control fibrinolysis,
      angiogenesis, steroidogesis, aromatization of androgens, proliferation and
      cytokine production. Many active substances (cytokines, growth factors, hormones
      and oxidative stress parameters) have been identified in endometriosis patients
      at different stages of the disease. In addition to the traditional diagnostic
      role of ultrasonography and CA 125, evidence is accumulating regarding a
      potential role sonorectovaginography. Currently the routine use of antiflammatory
      drugs and birth control pills is not supported by evidence. New protocols of
      medications incorporation new gonadotrophin releasing hormone agonists with add
      back therapy, androgenic agents and aromatase inhibitors have been proposed.
      Prospective randomiazed controlled trials proved that surgical treatment of
      endometriosis is better than placebo for endometriosis related pain and
      infertility for patients with stage I and II disease.

PMID- 19745796
TI  - Endometriosis and the role of reproductive medicine.
AB  - Endometriosis is a complex trait with significant environmental and genetic
      influences that are likely to affect its phenotype. Natural history of the
      disease varies from one individual to another. The gold standard of surgical
      diagnosis is limited in accuracy by visibility and recognition of lesions by the
      attending surgeon. Several lines of evidence suggest that pelvic endometriosis
      results from the reflux of viable endometrial tissue through the fallopian tubes.
      Endometriosis is an inflammatory disease that nuclear factor kappa B pathway may
      play an important role in its pathogenesis. Endometriotic lesions demonstrate
      increased aromatase expression in association with increased cyclo-oxygenase-2
      expression, especially in red lesions which represent earlier stages of
      inflammation. Estrogen and progesterone receptor expressions vary according to
      the morphology and the inflammatory status of the endometriotic lesions. Normal
      endometrial tissue fragments can adhere and implant to peritoneum. Aromatase
      expression, a possible intrinsic survival factor for endometrial tissue, is
      inducible in human endometrial fragments by androstenedione at physiological
      concentrations found in peritoneal fluid. Inflammatory response to ectopic
      endometrial tissue, which may vary in each individual seems to be important in
      disease progression. Current therapies for endometriosis include surgical and
      medical approaches aimed at cytoreduction or hormonal suppression. However, the
      disease have tendency to recur in many symptomatic women. Although new management
      approaches are emerging, properly designed clinical trials are desperately needed
      in treatment of pain and subfertility associated with endometriosis. Future
      studies should also focus on identifying risk population to develop preventive
      strategies, since the treatment of endometriosis is costly and challenging.

PMID- 19745797
TI  - The value of laparoscopic surgery to stage gynecological cancers: present and
      future.
AB  - The laparoscopic management of gynecologic cancers has been discussed
      controversely since decades. Much progress has been achieved technically enabling
      an experienced endoscopic surgeon to perform most of the gynecologic oncologic
      procedures such as hysterectomy, omentectomy, pelvic and paraaortic lymph node
      dissection. Although the value of laparoscopy with respect to oncological safety
      and patient's outcome has not been shown in prospective randomized clinical
      trials, many studies with altogether thousands of patients have revealed the
      feasibility and also similar oncologic results of laparoscopy when compared to
      laparotomy. Therefore, the laparoscopic approach has become well accepted for
      certain oncological indications, especially when early stage cancer cases are
      treated. These indications are also subject to ongoing Phase III trials: The
      LACC001 trial compares Total Laparoscopic Radical Hysterectomy (TLRH) or total
      robotic radical hysterectomy with total abdominal radical hysterectomy (TARH) for
      the treatment of early stage cervical cancer. The GOG LAP 2 and also the LACE001
      trial compare total laparoscopic hysterectomy (TLH) with total abdominal
      hysterectomy (TAH) for the treatment of early stage endometrial cancer, whereby
      bilateral salpingo-oophorectomy, pelvic and paraaortic lymph node dissection is
      performed according to tumor stage and grade. This review summarizes the current
      status of laparoscopy in gynecologic oncology based on the literature to date,
      the ongoing clinical trials, and the recommendations of the German Gynecologic
      Oncology Group (AGO).

PMID- 19745798
TI  - Robotic radical hysterectomy. A literature review.
AB  - Advanced laparoscopic procedures are increasingly being used as an alternative to
      laparotomy in gynecologic surgery. Several reviews have been completed that
      examine the advantages and drawbacks of this technique. Robotic technology offers
      the promise of overcoming many of the shortcomings of laparoscopy, while
      preserving classic operative techniques. This review article summarizes some of
      the most recent literature provided in the arena of robotic assisted radical
      hysterectomy for the treatment of cervical or endometrial cancer.

PMID- 19745799
TI  - Managing the complications associated with assisted reproductive technologies.
AB  - Delaying conception has increased the demand on assisted reproduction. Currently,
      more than 1% of children are conceived through assisted reproductive technologies
      (ART) worldwide and this number is likely to continue increasing. Like any other
      medical intervention ART is associated with both short-term and long-term
      complications. The major short-term complications include ovarian
      hyperstimulation syndrome (OHSS) and multiple pregnancies. OHSS is difficult to
      predict, but meticulous preventive strategies and protocols are being developed
      that may limit it. Most of the morbidities in children born after ART are related
      to multiple pregnancies. New laboratory methodologies may allow the transfer of
      fewer embryos to maintain satisfactory live birth rates while reducing the risk
      of multiple pregnancies. In vitro fertilization may be associated with a slight
      increased risk for birth defects. Analysis of possible risks from these
      techniques is confounded by factors of underlying parental subfertility,
      fertility treatments and multiple births. The long-term sequelae remain largely
      undetermined. All outcomes of ART, including pregnancy rates and adverse
      complications, need to be compared with standard non-ART when deciding the
      appropriate course of treatment. The importance of counselling should never be
      ignored in any treatment decision.

PMID- 19745800
TI  - [Analysis of a documental source of the Gynecological-Obstetric Institute of
      Milan. Year 1907].
AB  - The look I have at those origins of the obstetric assistance that are
      historically accepted, both as documental and narrative sources or monumental and
      instrumental ones, it is for some way very similar to the curious glance,
      fascinated and respectful of an archaeologist who begins to look and study some
      vestiges emerged from deep in the past. He looks to these rests as if he looked
      at so many evidences of men's lives that have passed through the history and at
      facts that have characterized the evolution of our society during the last
      centuries as well. The aim of this work was an historical source of the
      contemporary assistance. The purpose is the critical analysis and the
      interpretation of this source itself. The instruments involved in this work are:
      the description of the source, its intrinsic and extrinsic examination and the
      interpretation compared to the midwifery considered in the historic context. The
      followed method is the ''historical method'' suggested by Federico Chabod. As the
      choose document is in some way a ''no name'', before I enter in this
      historiographical examination, I believe it is convenient to describe the place
      where such document was born and has attended to its aims.

PMID- 19745801
TI  - Small cell carcinoma of the endometrium: report of a case and review of the
      literature.
AB  - Small cell carcinomas of the endometrium are rare and carry an ominous prognosis.
      Most patients present with advanced disease. The histopathological diagnosis
      requires immunohistochemistry confirmation and the tumor should be positive for a
      neuroendocrine marker. This article reports a new case and reviews the pertinent
      literature on the subject.

PMID- 19745802
TI  - [Severe hydroureteronephrosis due to deep infiltrating ureteral endometriosis].

PMID- 19745803
TI  - Oseltamivir-resistant 2009 pandemic influenza A (H1N1) virus infection in two
      summer campers receiving prophylaxis--North Carolina, 2009.
AB  - Initial testing of the 2009 pandemic influenza A (H1N1) virus found it
      susceptible to neuraminidase inhibitors (oseltamivir and zanamivir) and resistant
      to adamantanes (amantadine and rimantadine). Neuraminidase inhibitors have been
      used widely for treatment and chemoprophylaxis of 2009 pandemic influenza A
      (H1N1); however, sporadic cases of oseltamivir-resistant 2009 pandemic influenza
      A (H1N1) virus infection have been reported worldwide, including nine U.S. cases
      identified as of September 4. On July 14, CDC was contacted by a physician at a
      summer camp in North Carolina regarding two cases of influenza-like illness (ILI)
      in adolescent girls receiving oseltamivir chemoprophylaxis during an ILI outbreak
      that had begun June 18. The two girls stayed in the same cabin, and both received
      oseltamivir during a mass chemoprophylaxis program in which approximately 600
      campers and staff members received oseltamivir or zanamivir. On July 20 and July
      22, the North Carolina State Laboratory of Public Health confirmed pandemic H1N1
      virus infection in respiratory specimens from both girls. On August 14 and August
      19, CDC detected the H275Y mutation (N1 numbering) in neuraminidase from both
      specimens by pyrosequencing. The H275Y mutation is associated with resistance to
      oseltamivir; zanamivir susceptibility is retained. A second mutation (I223V) in
      neuraminidase also was detected in both specimens. This is the first report of
      oseltamivir resistance in pandemic H1N1 cases with an epidemiologic link. Health
      care providers should be aware that antiviral resistance can develop during
      chemoprophylaxis or treatment with subtherapeutic dosages and should follow
      published recommendations for antiviral medications.

PMID- 19745804
TI  - Receipt of influenza vaccine during pregnancy among women with live births-
      Georgia and Rhode Island, 2004-2007.
AB  - Pregnant women are at increased risk for complications from influenza. Since
      2004, the Advisory Committee on Immunization Practices (ACIP) and American
      College of Obstetricians and Gynecologists (ACOG) Committee on Obstetric Practice
      have recommended that all pregnant women be vaccinated with the trivalent
      inactivated vaccine during any trimester of pregnancy. To assess the percentage
      of women who were vaccinated during pregnancy among women with recent live
      births, CDC analyzed data from the Pregnancy Risk Assessment and Monitoring
      System (PRAMS) from Georgia and Rhode Island, the two states that collected this
      information on the PRAMS survey. This report summarizes the results, which showed
      that in Georgia, the prevalence of influenza vaccination during the woman's most
      recent pregnancy increased from 10.4% in 2004 to 15.5% in 2006. In Rhode Island,
      vaccination prevalence increased from 21.9% in 2004 to 33.4% in 2007. During 2006
      in Georgia, the most common reasons for not receiving vaccination were, "I don't
      normally get the flu vaccination" (69.4%), and "my physician did not mention
      anything about a flu vaccine during my pregnancy" (44.5%). Increased efforts are
      needed to assess vaccine coverage during pregnancy and to educate providers and
      pregnant women about ACIP and ACOG recommendations on providing intramuscular,
      inactivated influenza vaccine during any trimester of pregnancy.

PMID- 19745805
TI  - National laboratory inventories for wild poliovirus containment--Western Pacific
      region, 2008.
AB  - In the future, when wild poliovirus (WPV) transmission is interrupted worldwide,
      facilities holding WPV materials will represent the only remaining repository of
      the virus. Maintaining the number of such facilities at a minimum and at an
      appropriate biosafety standard (laboratory containment) reduces the risk for a
      facility-associated reintroduction of WPV. In May 1999, the World Health Assembly
      (WHA) urged all member states to begin the process leading to laboratory
      containment of WPV. The World Health Organization (WHO) global action plan for
      laboratory containment of WPV issued in 1999 indicated a staged approach that
      begins with a national survey of all biomedical facilities (Phase I); the purpose
      of the survey is to alert institutions and facilities to the need for
      containment, encourage reduction of WPV materials, and develop a national
      inventory of facilities holding such materials. The survey and inventory provide
      a facility database for use in all subsequent steps toward global poliovirus
      containment. In May 2008, WHA urged all WHO member states to complete Phase I
      activities outlined in the WHO Global Action Plan for Laboratory Containment of
      Wild Polioviruses. In the WHO Western Pacific Region (WPR), Phase I surveys of
      77,260 laboratories in the 37 countries and areas of WPR were conducted during
      1999--2008. A total of 45 laboratories were identified as holding WPV materials
      in 2008. This report describes completion of Phase I containment activities by
      WPR countries, and updates a previous report on Phase I completion in the
      European Region and global progress.

PMID- 19745806
TI  - A multi-compartment CNS neuron-glia Co-culture microfluidic platform.
AB  - We present a novel multi-compartment neuron co-culture microsystem platform for
      in vitro CNS axon-glia interaction research, capable of conducting up to six
      independent experiments in parallel for higher-throughput. We developed a new
      fabrication method to create microfluidic devices having both micro and macro
      scale structures within the same device through a single soft-lithography
      process, enabling mass fabrication with good repeatability. The multi-compartment
      microfluidic co-culture platform is composed of one soma compartment for neurons
      and six axon/glia compartments for oligodendrocytes (OLs). The soma compartment
      and axon/glia compartments are connected by arrays of axon-guiding microchannels
      that function as physical barriers to confine neuronal soma in the soma
      compartment, while allowing axons to grow into axon/glia compartments. OLs loaded
      into axon/glia compartments can interact only with axons but not with neuronal
      soma or dendrites, enabling localized axon-glia interaction studies. The
      microchannels also enabled fluidic isolation between compartments, allowing six
      independent experiments to be conducted on a single device for higher throughput.
      Soft-lithography using poly(dimethylsiloxane) (PDMS) is a commonly used technique
      in biomedical microdevices. Reservoirs on these devices are commonly defined by
      manual punching. Although simple, poor alignment and time consuming nature of the
      process makes this process not suitable when large numbers of reservoirs have to
      be repeatedly created. The newly developed method did not require manual punching
      of reservoirs, overcoming such limitations. First, seven reservoirs (depth: 3.5
      mm) were made on a poly(methyl methacrylate) (PMMA) block using a micro-milling
      machine. Then, arrays of ridge microstructures, fabricated on a glass substrate,
      were hot-embossed against the PMMA block to define microchannels that connect the
      soma and axon/glia compartments. This process resulted in macro-scale reservoirs
      (3.5 mm) and micro-scale channels (2.5 microm) to coincide within a single PMMA
      master. A PDMS replica that served as a mold master was obtained using soft
      lithography and the final PDMS device was replicated from this master. Primary
      neurons from E16-18 rats were loaded to the soma compartment and cultured for two
      weeks. After one week of cell culture, axons crossed microchannels and formed
      axonal only network layer inside axon/glia compartments. Axons grew uniformly
      throughout six axon/glia compartments and OLs from P1-2 rats were added to
      axon/glia compartments at 14 days in vitro for co-culture.

PMID- 19745807
TI  - Mechanism for the definition of elongation and termination by the class II CCA
      adding enzyme.
AB  - The CCA-adding enzyme synthesizes the CCA sequence at the 3' end of tRNA without
      a nucleic acid template. The crystal structures of class II Thermotoga maritima
      CCA-adding enzyme and its complexes with CTP or ATP were determined. The
      structure-based replacement of both the catalytic heads and nucleobase
      interacting neck domains of the phylogenetically closely related Aquifex aeolicus
      A-adding enzyme by the corresponding domains of the T. maritima CCA-adding enzyme
      allowed the A-adding enzyme to add CCA in vivo and in vitro. However, the
      replacement of only the catalytic head domain did not allow the A-adding enzyme
      to add CCA, and the enzyme exhibited (A, C)-adding activity. We identified the
      region in the neck domain that prevents (A, C)-adding activity and defines the
      number of nucleotide incorporations and the specificity for correct CCA addition.
      We also identified the region in the head domain that defines the terminal A
      addition after CC addition. The results collectively suggest that, in the class
      II CCA-adding enzyme, the head and neck domains collaboratively and dynamically
      define the number of nucleotide additions and the specificity of nucleotide
      selection.

PMID- 19745808
TI  - The making of a chloroplast.
AB  - Since its endosymbiotic beginning, the chloroplast has become fully integrated
      into the biology of the host eukaryotic cell. The exchange of genetic information
      from the chloroplast to the nucleus has resulted in considerable co-ordination in
      the activities of these two organelles during all stages of plant development.
      Here, we give an overview of the mechanisms of light perception and the
      subsequent regulation of nuclear gene expression in the model plant Arabidopsis
      thaliana, and we cover the main events that take place when proplastids
      differentiate into chloroplasts. We also consider recent findings regarding
      signalling networks between the chloroplast and the nucleus during seedling
      development, and how these signals are modulated by light. In addition, we
      discuss the mechanisms through which chloroplasts develop in different cell
      types, namely cotyledons and the dimorphic chloroplasts of the C(4) plant maize.
      Finally, we discuss recent data that suggest the specific regulation of the light
      dependent phases of photosynthesis, providing a means to optimize photosynthesis
      to varying light regimes.

PMID- 19745809
TI  - SnoN functions as a tumour suppressor by inducing premature senescence.
AB  - SnoN represses TGF-beta signalling to promote cell proliferation and has been
      defined as a proto-oncogene partly due to its elevated expression in many human
      cancer cells. Although the anti-tumourigenic activity of SnoN has been suggested,
      the molecular basis for this has not been defined. We showed here that high
      levels of SnoN exert anti-oncogenic activity by inducing senescence. SnoN
      interacts with the promyelocytic leukaemia (PML) protein and is recruited to the
      PML nuclear bodies where it stabilizes p53, leading to premature senescence.
      Furthermore, overexpression of SnoN inhibits oncogenic transformation induced by
      Ras and Myc in vitro and significantly blocks papilloma development in vivo in a
      carcinogen-induced skin tumourigenesis model. The few papillomas that were
      developed displayed high levels of senescence and spontaneously regressed. Our
      study has revealed a novel Smad-independent pathway of SnoN function that
      mediates its anti-oncogenic activity.

PMID- 19745810
TI  - A new plant protein interacts with eIF3 and 60S to enhance virus-activated
      translation re-initiation.
AB  - The plant viral re-initiation factor transactivator viroplasmin (TAV) activates
      translation of polycistronic mRNA by a re-initiation mechanism involving
      translation initiation factor 3 (eIF3) and the 60S ribosomal subunit (60S).
      QJ;Here, we report a new plant factor-re-initiation supporting protein (RISP)
      that enhances TAV function in re-initiation. RISP interacts physically with TAV
      in vitro and in vivo. Mutants defective in interaction are less active, or
      inactive, in transactivation and viral amplification. RISP alone can serve as a
      scaffold protein, which is able to interact with eIF3 subunits a/c and 60S,
      apparently through the C-terminus of ribosomal protein L24. RISP pre-bound to
      eIF3 binds 40S, suggesting that RISP enters the translational machinery at the
      43S formation step. RISP, TAV and 60S co-localize in epidermal cells of infected
      plants, and eIF3-TAV-RISP-L24 complex formation can be shown in vitro. These
      results suggest that RISP and TAV bridge interactions between eIF3-bound 40S and
      L24 of 60S after translation termination to ensure 60S recruitment during
      repetitive initiation events on polycistronic mRNA; RISP can thus be considered
      as a new component of the cell translation machinery.

PMID- 19745811
TI  - Pre-fibrillar alpha-synuclein variants with impaired beta-structure increase
      neurotoxicity in Parkinson's disease models.
AB  - The relation of alpha-synuclein (alphaS) aggregation to Parkinson's disease (PD)
      has long been recognized, but the mechanism of toxicity, the pathogenic species
      and its molecular properties are yet to be identified. To obtain insight into the
      function different aggregated alphaS species have in neurotoxicity in vivo, we
      generated alphaS variants by a structure-based rational design. Biophysical
      analysis revealed that the alphaS mutants have a reduced fibrillization
      propensity, but form increased amounts of soluble oligomers. To assess their
      biological response in vivo, we studied the effects of the biophysically defined
      pre-fibrillar alphaS mutants after expression in tissue culture cells, in
      mammalian neurons and in PD model organisms, such as Caenorhabditis elegans and
      Drosophila melanogaster. The results show a striking correlation between alphaS
      aggregates with impaired beta-structure, neuronal toxicity and behavioural
      defects, and they establish a tight link between the biophysical properties of
      multimeric alphaS species and their in vivo function.

PMID- 19745812
TI  - The E2F functional analogue SBF recruits the Rpd3(L) HDAC, via Whi5 and Stb1, and
      the FACT chromatin reorganizer, to yeast G1 cyclin promoters.
AB  - Regulation of the CLN1 and CLN2 G1 cyclin genes controls cell cycle progression.
      The SBF activator binds to these promoters but is kept inactive by the Whi5 and
      Stb1 inhibitors. The Cdc28 cyclin-dependent kinase phosphorylates Whi5, ending
      the inhibition. Our chromatin immunoprecipitation (ChIP) experiments show that
      SBF, Whi5 and Stb1 recruit both Cdc28 and the Rpd3(L) histone deacetylase to CLN
      promoters, extending the analogy with mammalian G1 cyclin promoters in which Rb
      recruits histone deacetylases. Finally, we show that the SBF subunit Swi6
      recruits the FACT chromatin reorganizer to SBF- and MBF-regulated genes.
      Mutations affecting FACT reduce the transient nucleosome eviction seen at these
      promoters during a normal cell cycle and also reduce expression. Temperature
      sensitive mutations affecting FACT and Cdc28 can be suppressed by disruption of
      STB1 and WHI5, suggesting that one critical function of FACT and Cdc28 is
      overcoming chromatin repression at G1 cyclin promoters. Thus, SBF recruits
      complexes to promoters that either enhance (FACT) or repress (Rpd3L)
      accessibility to chromatin, and also recruits the kinase that activates START.

PMID- 19745813
TI  - Myc-regulated microRNAs attenuate embryonic stem cell differentiation.
AB  - Myc proteins are known to have an important function in stem cell maintenance. As
      Myc has been shown earlier to regulate microRNAs (miRNAs) involved in
      proliferation, we sought to determine whether c-Myc also affects embryonic stem
      (ES) cell maintenance and differentiation through miRNAs. Using a quantitative
      primer-extension PCR assay we identified miRNAs, including, miR-141, miR-200, and
      miR-429 whose expression is regulated by c-Myc in ES cells, but not in the
      differentiated and tumourigenic derivatives of ES cells. Chromatin
      immunoprecipitation analyses indicate that in ES cells c-Myc binds proximal to
      genomic regions encoding the induced miRNAs. We used expression profiling and
      seed homology to identify genes specifically downregulated both by these miRNAs
      and by c-Myc. We further show that the introduction of c-Myc-induced miRNAs into
      murine ES cells significantly attenuates the downregulation of pluripotency
      markers on induction of differentiation after withdrawal of the ES cell
      maintenance factor LIF. In contrast, knockdown of the endogenous miRNAs
      accelerate differentiation. Our data show that in ES cells c-Myc acts, in part,
      through a subset of miRNAs to attenuate differentiation.

PMID- 19745814
TI  - Zfh1 promotes survival of a peripheral glia subtype by antagonizing a Jun N
      terminal kinase-dependent apoptotic pathway.
AB  - In Drosophila subperineurial glia (SPG) ensheath and insulate the nerve. SPG is
      under strict cell cycle and survival control because cell division or death of
      such a cell type would compromise the integrity of the blood-nerve barrier. The
      mechanisms underlying the survival of SPG remain unknown. Here, we show that the
      embryonic peripheral glia expresses the Zfh1 transcription factor, and in zfh1
      mutants a particular SPG subtype, ePG10, undergoes apoptosis. Our findings show
      that in ePG10, Zfh1 represses the pro-apoptotic RHG-motif gene reaper in a cell
      autonomous manner. Zfh1 also blocks the activation of the Jun N-terminal kinase
      (JNK) pathway, and reducing or enhancing JNK signalling in zfh1 mutants prevents
      or promotes ePG10 apoptosis. Our study shows a novel function for Zfh1 as an anti
      apoptotic molecule and uncovers a cryptic JNK-dependent apoptotic programme in
      ePG10, which is normally blocked by Zfh1. We propose that, in cells such as SPG
      that do not undergo self-renewal and survive long periods, transcriptional
      control of RHG-motif gene expression together with fine tuning of JNK signalling
      is crucial for cell survival.

PMID- 19745815
TI  - Mitochondrial 'kiss-and-run': interplay between mitochondrial motility and fusion
      fission dynamics.
AB  - Visualizing mitochondrial fusion in real time, we identified two classes of
      fusion events in mammalian cells. In addition to complete fusion, we observed
      transient fusion events, wherein two mitochondria came into close apposition,
      exchanged soluble inter-membrane space and matrix proteins, and re-separated,
      preserving the original morphology. Transient fusion exhibited rapid kinetics of
      the sequential and separable mergers of the outer and inner membranes, but
      allowed only partial exchange of integral membrane proteins. When the inner
      membrane fusion protein Opa1 level was lowered or was greatly elevated, transient
      fusions could occur, whereas complete fusions disappeared. Furthermore, transient
      fusions began from oblique or lateral interactions of mitochondria associated
      with separate microtubules, whereas complete fusions resulted from longitudinal
      merging of organelles travelling along a single microtubule. In contrast to
      complete fusion, transient fusions both required and promoted mitochondrial
      motility. Transient fusions were also necessary and sufficient to support
      mitochondrial metabolism. Thus, Opa1 expression and cytoskeletal anchorage govern
      a novel form of fusion that has a distinct function in mitochondrial maintenance.

PMID- 19745816
TI  - Substrate-driven conformational changes in ClC-ec1 observed by fluorine NMR.
AB  - The CLC 'Cl(-) channel' family consists of both Cl(-)/H(+) antiporters and Cl(-)
      channels. Although CLC channels can undergo large, conformational changes
      involving cooperativity between the two protein subunits, it has been
      hypothesized that conformational changes in the antiporters may be limited to
      small movements localized near the Cl(-) permeation pathway. However, to date few
      studies have directly addressed this issue, and therefore little is known about
      the molecular movements that underlie CLC-mediated antiport. The crystal
      structure of the Escherichia coli antiporter ClC-ec1 provides an invaluable
      molecular framework, but this static picture alone cannot depict the protein
      movements that must occur during ion transport. In this study we use fluorine
      nuclear magnetic resonance (NMR) to monitor substrate-induced conformational
      changes in ClC-ec1. Using mutational analysis, we show that substrate-dependent
      (19)F spectral changes reflect functionally relevant protein movement occurring
      at the ClC-ec1 dimer interface. Our results show that conformational change in
      CLC antiporters is not restricted to the Cl(-) permeation pathway and show the
      usefulness of (19)F NMR for studying conformational changes in membrane proteins
      of known structure.

PMID- 19745817
TI  - Relationship between self-reported sleep duration and changes in circadian blood
      pressure.
AB  - BACKGROUND: Abnormalities in sleep duration and circadian blood pressure (BP)
      rhythm are both independently associated with increased risk of death and
      cardiovascular disease. The relationship, however, between these two entities
      remains unclear. This study was undertaken to determine whether abnormal sleep
      duration is associated with nondipping status and elevated morning surge.
      METHODS: In a cross-sectional study, we assessed the relationship between self
      reported sleep duration and circadian BP profiles from 24-h ambulatory BP
      monitoring (ABPM) in 108 normotensive and 417 hypertensive subjects, independent
      of relevant sociodemographic, anthropometric, and medical factors. RESULTS: On
      average, subjects reported sleeping 6.5 +/- 1.7 h with 18.5% sleeping < or =5 h
      and 7.6%, > or =9 h. There were 199 (37.9%) nondippers in our cohort and the mean
      morning surge was 18.7 +/- 1.7 mm Hg. The adjusted odds ratio for nondipping
      (<10% nocturnal systolic BP fall) associated with a 1-h decrement in sleep
      duration was 1.12 (P = 0.04) and with age per 5-year increment, 1.15 (P =
      0.0003). The adjusted odds ratio for an elevated morning surge (> or =18.0 mm Hg)
      associated with a 1-h increment in sleep duration was 1.13 (P = 0.02).
      CONCLUSIONS: Our study indicates that a sleep deficit is associated with
      nondipping and a decreased morning surge, whereas a sleep surfeit is associated
      with less nondipping and an increased morning surge. These findings provide a
      possible link for the heightened risk of cardiovascular disease associated with
      disturbances in circadian BP rhythm and the extremes of sleep quantity.

PMID- 19745818
TI  - Prehypertension in outpatient obese children.
AB  - BACKGROUND: The aim of the study was to analyze the prevalence of prehypertension
      (PH) in obese (OB) children and its relation with estimated glomerular filtration
      rate (eGFR) and left ventricular (LV) function. METHODS: The study included 447
      OB and 131 normal-weight children. PH was defined according to the criteria
      proposed by the National High Blood Pressure Education Program Working Group on
      High Blood Pressure in Children and Adolescents. Insulin sensitivity was
      evaluated by HOMA(IR), and eGFR was calculated by Schwartz's formula. LV function
      was analyzed by echocardiography in 165 OB children. RESULTS: PH was observed in
      79 OB children (17.7%) and in 2 (1.5%) controls. Among OB children, those with PH
      had greater percentage of males (P < 0.05), higher level of body mass index (BMI)
      (P < 0.001), waist circumference (WC) (P < 0.005), and HOMA(IR) (P < 0.001),
      compared to PH- children. The two groups did not differ for eGFR and LV function.
      At logistic regression analysis, PH was independently associated with male gender
      (P < 0.025) and HOMA(IR) (P < 0.002). Gender analysis showed that boys with PH
      presented higher levels of BMI (P < 0.005), WC (P < 0.01), HOMA(IR) (P < 0.001),
      and triglycerides (P < 0.005) compared to PH- boys. Females with PH were older
      and in more advanced postpubertal stage, had higher BMI, WC (P < 0.05, for all),
      and HOMA(IR) (P < 0.025), compared to PH- girls. CONCLUSIONS: In a population of
      outpatient OB children, the prevalence of PH was 17.7% and boys were more likely
      than girls to have PH. This condition is characterized by insulin resistance in
      both sexes but no impairment in glomerular and LV function.

PMID- 19745819
TI  - Blood pressure and progression of cerebral atrophy in patients with vascular
      disease.
AB  - BACKGROUND: Cerebral atrophy on brain magnetic resonance imaging (MRI) has been
      associated with vascular risk factors including hypertension. Progression of
      cerebral atrophy and its risk factors have not been studied in vascular disease
      patients. This study aimed to assess the progression of cerebral atrophy and to
      evaluate possible associations with blood pressure (BP) in patients with pre
      existing vascular disease. METHODS: A total of 331 patients with manifest
      vascular disease from the Second Manifestations of ARTerial Disease (SMART) Study
      underwent baseline and follow-up MRI scanning (mean follow-up 4.1 +/- 0.3 years).
      The annual change in brain and ventricular volume was calculated with an
      automated quantitative volumetric method. Associations between BP and change in
      brain and ventricular volumes and between BP and the occurrence of lacunar
      infarcts were analyzed. RESULTS: At baseline mean age was 58 +/- 9 years and mean
      BP was 138/80 mm Hg. Mean annual decrease in brain tissue volume was 6.5 +/- 3.8
      ml and mean annual increase in ventricular volume was 1.0 +/- 1.0 ml. There was
      no association observed between BP and annual change in brain or ventricular
      volume, but a clear association was found between BP and incident lacunar
      infarcts (odds ratio 1.57; 1.11-2.22 per s.d. increase in systolic BP (SBP)).
      CONCLUSIONS: The magnitude of changes in brain tissue and ventricular volume in
      patients with vascular disease was comparable to the physiological changes
      described in normal people at a much higher age. Progression of cerebral atrophy
      in this population may be associated with advanced physiological aging, but is
      probably not caused by elevated BP.

PMID- 19745820
TI  - Effects of diabetes mellitus, pressure-overload and their association on
      myocardial structure and function.
AB  - BACKGROUND: Structural and functional changes involved in cardiac injury induced
      by diabetes mellitus, pressure-overload, or both conditions were evaluated.
      METHODS: Pressure-overload was established by suprarenal aortic banding in rats.
      Six weeks later, diabetes was induced by streptozotocin (STZ, 65 mg/kg,
      intraperitoneally), resulting in four groups: SHAM, banded (BA), diabetic (DM),
      and diabetic-banded (DM-BA). On the 12th week, left ventricular (LV) structure
      and function were evaluated. LV function was assessed in vivo with pressure
      volume catheters and in vitro by papillary muscles' performance at baseline and
      in response to isoprenaline (ISO, 10(-8) to 10(-5) M). RESULTS: Compared to SHAM,
      we observed a significant increase of type-B natriuretic peptide (BA = 370 +/-
      110%; DM-BA = 580 +/- 210%), LV mass (BA = 36.8 +/- 3.6%; DM-BA = 32.1 +/- 3.1%),
      cardiomyocyte diameter (BA = 19.5 +/- 2.3%; DM = 14.3 +/- 1.9%; DM-BA = 11.4 +/-
      2.0%), fibrosis (BA = 85 +/- 14%; DM = 145 +/- 28%; DM-BA = 155 +/- 14%),
      advanced glycation end-product (AGE) deposition (DM = 141 +/- 29%; DM-BA = 166 +/
      46%), contraction (tAT: DM = 13.7 +/- 2.4%; DM-BA = 26.3 +/- 7.1%); a delayed
      relaxation (tHR: DM = 13.8 +/- 2.6%; DM-BA = 25.5 +/- 9.2%) and a decrease of
      collagen type-I/type-III ratio (DM = -66.1 +/- 4.6%; DM-BA = -51.9 +/- 5.5). In
      SHAM animals, ISO (10(-5) M) increased 86.5 +/- 26.2% active tension, 105.3 +/-
      20.2% dT/dt(max), and 166.8 +/- 29.9% dT/dt(min). Similar effects were observed
      in BA and DM animals, whereas in DM-BA these inotropic and lusitropic responses
      were blunted. Moreover, at a similar resting muscle length, ISO decreased passive
      tension by 12 +/- 3% in SHAM and 11 +/- 3% in BA, indicating an increase in
      myocardial distensibility, an effect that was absent in both diabetic groups.
      CONCLUSION: Long-standing pressure-overload increased LV mass, while diabetes
      promoted AGE and collagen deposition, which might explain the abolition of ISO
      induced increased myocardial distensibility. Association of pressure-overload and
      diabetes completely blunted the inotropic and lusitropic responses to ISO, with
      no additional structural damages than in pressure-overload or diabetes alone.

PMID- 19745821
TI  - Effects of 17-hydroxyprogesterone on tumor necrosis factor-alpha-induced
      hypertension during pregnancy.
AB  - BACKGROUND: Inflammatory cytokines such as tumor necrosis factor-alpha (TNF
      alpha) may be an important link between placental ischemia and hypertension in
      preeclampsia. We examined the effect of 17-hydroxyprogesterone caproate (17-OHP)
      on TNF-alpha-stimulated endothelin (ET) production and hypertension during
      pregnancy. METHODS: TNF-alpha-stimulated ET was examined from endothelial cells
      cultured in the presence and absence of progesterone. Blood pressure and tissue
      ET-1 were measured in the following groups of pregnant rats: controls, 17-OHP
      (3.32 mg/kg), TNF-alpha treated (50 ng/day), TNF-alpha treated+17-OHP. RESULTS:
      Progesterone abolished TNF-alpha-stimulated ET-1 from endothelial cells. TNF
      alpha-induced hypertension was associated with significant increases in renal and
      placental ET-1. Administration of 17-OHP attenuated TNF-alpha-induced
      hypertension and decreased renal ET-1. CONCLUSION: Progesterone directly
      abolished TNF-alpha-stimulated ET-1 and attenuated TNF-alpha-induced
      hypertension, possibly via suppression of the renal ET-1 system. These data
      suggest that treatment with progesterone of hypertension associated with elevated
      cytokines during pregnancy may be worthy of further consideration.

PMID- 19745822
TI  - Quantitative imaging of collective cell migration during Drosophila gastrulation:
      multiphoton microscopy and computational analysis.
AB  - This protocol describes imaging and computational tools to collect and analyze
      live imaging data of embryonic cell migration. Our five-step protocol requires a
      few weeks to move through embryo preparation and four-dimensional (4D) live
      imaging using multi-photon microscopy, to 3D cell tracking using image
      processing, registration of tracking data and their quantitative analysis using
      computational tools. It uses commercially available equipment and requires
      expertise in microscopy and programming that is appropriate for a biology
      laboratory. Custom-made scripts are provided, as well as sample datasets to
      permit readers without experimental data to carry out the analysis. The protocol
      has offered new insights into the genetic control of cell migration during
      Drosophila gastrulation. With simple modifications, this systematic analysis
      could be applied to any developing system to define cell positions in accordance
      with the body plan, to decompose complex 3D movements and to quantify the
      collective nature of cell migration.

PMID- 19745823
TI  - Time-resolved RNA SHAPE chemistry: quantitative RNA structure analysis in one
      second snapshots and at single-nucleotide resolution.
AB  - RNA selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE)
      chemistry exploits the discovery that conformationally dynamic nucleotides
      preferentially adopt configurations that facilitate reaction between the 2'-OH
      group and a hydroxyl-selective electrophile, such as benzoyl cyanide (BzCN), to
      form a 2'-O-adduct. BzCN is ideally suited for quantitative, time-resolved
      analysis of RNA folding and ribonucleoprotein (RNP) assembly mechanisms because
      this reagent both reacts with flexible RNA nucleotides and also undergoes auto
      inactivating hydrolysis with a half-life of 0.25 s at 37 degrees C. RNA folding
      is initiated by addition of Mg(2+) or protein, or other change in solution
      conditions, and nucleotide resolution structural images are obtained by adding
      aliquots of the evolving reaction to BzCN and then 'waiting' for 1 second. Sites
      of the 2'-O-adduct formation are subsequently scored as stops to primer extension
      using reverse transcriptase. This time-resolved SHAPE protocol makes it possible
      to obtain 1-second structural snapshots in time-resolved kinetic studies for RNAs
      of arbitrary length and complexity in a straightforward and concise experiment.

PMID- 19745824
TI  - Chemical genetic screening in the zebrafish embryo.
AB  - Chemical genetic screening can be described as a discovery approach in which
      chemicals are assayed for their effects on a defined biological system. The
      zebrafish, Danio rerio, is a well-characterized and genetically tractable
      vertebrate model organism that produces large numbers of rapidly developing
      embryos that develop externally. These characteristics allow for flexible, rapid
      and scalable chemical screen design using the zebrafish. We describe a protocol
      for screening compounds from a chemical library for effects on early zebrafish
      development using an automated in situ based read-out. As screenings are carried
      out in the context of a complete, developing organism, this approach allows for a
      more comprehensive analysis of the range of a chemical's effects than that
      provided by, for example, a cell culture-based or in vitro biochemical assay.
      Using a 24-h chemical treatment, one can complete a round of screening in 6 d.

PMID- 19745825
TI  - Highly efficient subcloning of rodent malaria parasites by injection of single
      merosomes or detached cells.
AB  - This protocol describes a method for obtaining rodent Plasmodium parasite clones
      with high efficiency, which takes advantage of the normal course of Plasmodium in
      vitro exoerythrocytic development. At the completion of development, detached
      cells/merosomes form, which contain hundreds to thousands of merozoites. As all
      parasites within a single detached cell/merosome derive from the same sporozoite,
      we predicted them to be genetically identical. To prove this, hepatoma cells were
      infected simultaneously with a mixture of Plasmodium berghei sporozoites
      expressing either GFP or mCherry. Subsequently, individual detached
      cells/merosomes from this mixed population were selected and injected into mice,
      resulting in clonal blood stage parasite infections. Importantly, as a large
      majority of mice become successfully infected using this protocol, significantly
      less mice are necessary than for the widely used technique of limiting dilution
      cloning. To produce a clonal P. berghei blood stage infection from a non-clonal
      infection using this procedure requires between 4 and 5 weeks.

PMID- 19745826
TI  - Prevalence and predictors of renal artery stenosis in hypertensive patients
      undergoing coronary angiography.
AB  - Renal artery stenosis (RAS) is a major comorbid condition in patients with
      coronary artery disease (CAD). Although the reported prevalence of significant
      RAS among patients undergoing coronary angiography varies from 6.2 to 28% in
      Western countries, little information is available on the prevalence and
      predictors of RAS in Middle Eastern countries. From April 2007 to May 2008, 732
      hypertensive patients with suspected CAD immediately after selective coronary
      angiography underwent abdominal aortography with or without selective renal
      angiography. Coronary angiography revealed stenosis of > or =50% in at least one
      of the main coronary vessels in 434 (59.3%) patients, including 100 (13.7%) cases
      with single-vessel CAD, 114 (15.6%) with two-vessel CAD and 220 (30.1%) with
      three-vessel CAD. Significant RAS was present in 87 patients (11.9%), severe (>
      or =75%) RAS in 35 patients (4.8%) and bilateral RAS in 37 patients (5.1%).
      Higher serum creatinine level, severity of CAD, history of coronary artery bypass
      graft surgery (CABG), congestive heart failure, and pulmonary edema together with
      atrial fibrillation were the most powerful predictors of significant RAS. In
      multivariate logistic regression analysis, three-vessel CAD (odds ratio 1.61, 95%
      confidence interval (1.36-1.91), P<0.001), history of CABG (odds ratio 4.40, 95%
      confidence interval (1.17-16.5), P=0.028) and serum creatinine level of >1.2 mg
      per 100 ml (odds ratio 2.12, 95% confidence interval (1.09-4.12), P=0.026) were
      the most powerful predictors of significant RAS. The prevalence of RAS in our
      patients was similar to that reported in the Western countries. The presence of
      multi-vessel CAD or a history of CABG along with a higher serum creatinine level
      in hypertensive patients undergoing coronary angiography was found to be a risk
      factor for RAS.

PMID- 19745827
TI  - Antihypertensive, antidyslipidemic and endothelial modulating activities of
      Orchis mascula.
AB  - The objective of this study was to investigate the possible mode(s) of action for
      the medicinal use of Orchis mascula (OM) (family Orchidaceae) in hypertension and
      dyslipidemia. In spontaneously hypertensive rats (SHRs), OM significantly
      (P<0.05) reduced systolic blood pressure to 174.2+/-9.63 vs. 203.4+/-7.13 mm Hg
      (mean+/-s.e.m.; n=7-10) and improved endothelial dysfunction by increasing
      acetylcholine-induced relaxation. In normotensive anesthetized rats, the crude
      extract of OM (Om.Cr) at 10 and 30 mg kg(-1) caused a dose-dependent attenuation
      of mean arterial pressure. OM also decreased serum triglycerides to 29.28+/-6.99
      vs. 93.84+/-5.7 mg per 100 ml (P<0.001), low-density lipoprotein-cholesterol to
      5.99+/-1.27 vs. 21.9+/-3.5 mg per 100 ml (P<0.05) and atherogenic index to
      0.096+/-0.017 vs. 0.36+/-0.08 mg per 100 ml (P<0.05). OM significantly reduced
      lipid levels in tyloxapol and high fat diet-induced hyperlipidemia. In a second
      model, OM also reduced gain in body weight with a reduction in daily diet
      consumption. In isolated rabbit aorta, Om.Cr caused concentration-dependent
      relaxation of both phenylephrine and high K(+) (80 mM)-induced contractions and a
      rightward shift of the calcium concentration-response curves similar to the
      effect seen with verapamil. In conclusion, OM shows antihypertensive and
      endothelial-modulating effects mediated through multiple pathways that include
      direct vasodilation by calcium channel blockade and reduction of plasma lipids by
      inhibition of biosynthesis, absorption and secretion. This study rationalizes the
      medicinal use of OM in hypertension and dyslipidemia. However, further studies
      are required to identify the active constituents of this plant.

PMID- 19745828
TI  - Benefits of the angiotensin II receptor antagonist olmesartan in controlling
      hypertension and cerebral hemodynamics after stroke.
AB  - The purpose of this study was to assess the relative benefits of angiotensin II
      receptor blockers (ARBs) and calcium channel blockers (CCBs) on cerebral
      hemodynamics and rehabilitation outcome in hypertensive stroke patients. We
      randomly assigned 35 patients to either the olmesartan (n=18) or amlodipine
      (n=17) treatment groups for 8 weeks. Changes in cerebral blood flow (CBF) and
      cerebrovascular reserve capacity (CRC) were quantified using xenon-CT and
      rehabilitation parameters were also measured. Over 24 h, olmesartan and
      amlodipine both reduced blood pressure (BP) to similar levels (systolic BP, 
      16.1+/-2.7 mm Hg vs. -15.7+/-3.1; diastolic BP, -9.2+/-2.9 vs. -8.6+/-3.3 mm Hg,
      respectively). In olmesartan-treated patients, CBF significantly increased in the
      affected and unaffected hemispheres, and CRC increased significantly in the
      affected hemisphere. No increases in CBF and CRC were observed in amlodipine
      treated patients. Patients treated with olmesartan showed effective rates of
      improvement in hand (30.0%), upper extremities (40.0%) and lower extremities
      (100.0%), measured by Brunnstrom stage; these improvements were significantly
      different from those in amlodipine-treated patients for the total (P<0.02) and
      lower extremity (P<0.05) scores. There were no significant differences in Barthel
      indices and Mini-Mental State Examination (MMSE) scores. Olmesartan, but not
      amlodipine, had beneficial effects on CBF, CRC and rehabilitation outcomes in
      hypertensive stroke patients, by a mechanism independent of BP reduction and
      possibly by normalizing CBF autoregulation. Our results suggest that olmesartan
      may improve cerebral circulation and rehabilitation in hypertensive stroke
      patients in whom CBF autoregulation is impaired.

PMID- 19745829
TI  - PH domain leucine-rich repeat protein phosphatase 1 contributes to maintain the
      activation of the PI3K/Akt pro-survival pathway in Huntington's disease striatum.
AB  - Dysregulation of gene expression is one of the mechanisms involved in the
      pathophysiology of Huntington's disease (HD). Here, we examined whether mutant
      huntingtin regulates the levels of PH domain leucine-rich repeat protein
      phosphatase 1 (PHLPP1), a phosphatase that specifically dephosphorylates Akt at
      Ser473. Our results show decreased PHLPP1 protein levels in knock-in models
      (Hdh(Q111/Q111) mouse striatum and STHdh(Q111/Q111) cells), in the striatum of N
      terminal exon-1 mutant huntingtin transgenic mouse models (R6/1; R6/1 : BDNF + or
      - , R6/2 and Tet/HD94) and in the putamen of HD patients. Quantitative PCR
      analysis revealed a reduction in PHLPP1 mRNA levels in the striatum of R6/1
      compared with wild-type mice. Coincident with reduced PHLPP1 protein levels, we
      observed increased phosphorylated Akt (Ser473) levels specifically in the
      striatum. The analysis of the conditional mouse model Tet/HD94 disclosed that
      after mutant huntingtin shutdown PHLPP1 levels returned to wild-type levels
      whereas phospho-Akt levels were partially reduced. In conclusion, our results
      show that mutant huntingtin downregulates PHLPP1 expression. In the striatum,
      these reduced levels of PHLPP1 can contribute to maintain high levels of
      activated Akt that may delay cell death and allow the recovery of neuronal
      viability after mutant huntingtin silencing.

PMID- 19745830
TI  - TSC-22D1 isoforms have opposing roles in mammary epithelial cell survival.
AB  - Transforming growth factor beta (TGFbeta)-stimulated clone-22 domain family
      member 1 (TSC-22D1) has previously been associated with enhanced apoptosis in
      several cell systems. In an attempt to identify novel factors that are involved
      in the control of cell death during mammary gland involution, we found that the
      mRNA for isoform 2 of TSC-22D1 was highly upregulated 24 h after forced weaning,
      when a dramatic increase in cell death occurred, closely following the expression
      of the known inducer of cell death during involution, TGFbeta3. This was
      paralleled by strongly increased TSC-22D1 isoform 2 protein levels in the luminal
      epithelium. In contrast, RNA and protein expression levels of the isoform 1 of
      TSC-22D1 did not change during development. Whereas isoform 2 induced cell death,
      isoform 1 suppressed TGFbeta-induced cell death and enhanced proliferation in
      mammary epithelial cell lines. Furthermore, four distinct forms of isoform 2
      protein were detected in the mammary gland, of which only a 15-kDa form was
      associated with early involution. Our data describe novel opposing functions of
      the two mammalian TSC-22D1 isoforms in cell survival and proliferation, and
      establish the TSC-22D1 isoform 2 as a potential regulator of cell death during
      mammary gland involution.

PMID- 19745831
TI  - Single-cell quantification of Bax activation and mathematical modelling suggest
      pore formation on minimal mitochondrial Bax accumulation.
AB  - Mitochondrial outer membrane permeabilisation (MOMP) during apoptosis is
      triggered by the activation and oligomerisation of Bax and Bak, but a
      quantification of these processes in individual cells has not yet been performed.
      Single-cell imaging of Bax translocation and oligomerisation in Bax-deficient DU
      145 cells expressing CFP-Bax and YFP-Bax revealed that both processes started
      only minutes before or concomitantly with MOMP, with the majority of Bax
      translocation and oligomerisation occurring downstream of MOMP. Quantification of
      YFP-Bax concentrations at mitochondria revealed an increase of only 1.8 + or -
      1.5% at MOMP onset. This was increased to 11.2 + or - 3.6% in bak-silenced cells.
      These data suggested that Bax activation exceeded by far the quantities required
      for MOMP induction, and that minimal Bax or Bak activation may be sufficient to
      trigger rapid pore formation. In a cellular automaton modelling approach that
      incorporated the quantities and movement probabilities of Bax and its inhibitors,
      activators and enablers in the mitochondrial membrane, we could re-model rapid
      pore formation kinetics at submaximal Bax activation.

PMID- 19745832
TI  - Insights on human evolution: an analysis of Alu insertion polymorphisms.
AB  - We analyzed the genetic profile of 563 individuals from 12 geographically
      targeted human populations from Europe, Asia and Africa using 27 human-specific
      polymorphic Alu insertions. Phylogenetic analyses indicated a clear
      correspondence between genetic profiles and historical patterns of gene flow and
      genetic drift. Sub-Saharan African populations (Benin, Cameroon, Kenya and
      Rwanda) formed a visibly differentiated cluster, indicating the role of the
      Sahara desert as a strong natural barrier to gene flow. Moreover, a higher than
      expected genetic affinity between populations from Europe, North Africa and Asia
      was detected, probably reflecting the homogenizing effects of bidirectional
      migratory processes between Eurasia and North Africa during the Plio-Pleistocene
      and Neolithic periods or the insensitivity of these markers in discriminating
      between these groups. The Ami aborigines of Formosa present a distinctive degree
      of genetic uniqueness from all the other groups, consistent with a pattern of
      isolation by distance, small population size and, accordingly, substantial
      genetic drift. We further tested all 27 Alu loci for their potential usefulness
      as ancestry informative markers (AIMs). On the basis of differences between
      weighted allelic frequencies (delta-values) and F(ST) values, we propose that 11
      of the 27 Alu elements could be useful as part of the current AIM panels to
      assess phylogenetic relationships.

PMID- 19745833
TI  - Polymorphisms and haplotypes in TLR9 and MYD88 are associated with the
      development of Hodgkin's lymphoma: a candidate-gene association study.
AB  - Toll-like receptors (TLRs) and myeloid differentiation primary response protein
      88 (MYD88) gene polymorphisms may be involved in the pathogenesis of Hodgkin's
      lymphoma (HL) through altered immunoregulatory and inflammatory responses. A
      candidate-gene association study was conducted to investigate the association
      between TLR9 -1237T>C, TLR9 2848A>G, MYD88 -938C>A and MYD88 1944C>G gene
      polymorphisms and the risk for HL. The impact of haplotypes was also examined.
      The study showed that carriership for -1237C and 2848A was associated with an
      increased risk for HL (odds ratio (OR)=2.53 (1.36-4.71) and OR=6.20 (1.3-28.8)).
      The MYD88 polymorphisms produced nonsignificant results. The estimated
      frequencies of the TLR9/1237C-2848A and MYD88/938C-1944G haplotypes were also
      significantly different between HL and controls (P<0.01). In addition, a
      significant difference between HL and controls was observed for the TLR9/1237C
      TLR9/2848A-MYD88/938C-MYD88/1944C haplotypes (P<0.01). In conclusion, our study
      showed that TLR polymorphisms, and TLR9 and MYD88 haplotypes are related to the
      development of HL.

PMID- 19745834
TI  - A 3-bp deletion of mitochondrial DNA tRNALys observed in lymphoblastoid cells.

PMID- 19745835
TI  - ACTA2 is not a major disease-causing gene for moyamoya disease.

PMID- 19745836
TI  - Haemorrhagic pigment epithelial detachment as a predictive feature of polypoidal
      choroidal vasculopathy in a Chinese population.
AB  - PURPOSE: To determine the frequency of haemorrhagic pigment epithelial detachment
      (PED) among patients presenting with either polypoidal choroidal vasculopathy
      (PCV) or choroidal neovascularization (CNV) and calculate the degree to which the
      presence of a haemorrhagic PED can be used to predict the diagnosis of PCV.
      METHODS: A retrospective review of 290 eyes of 253 patients presenting to the
      Singapore National Eye Centre with serosanguineous maculopathy. Patients
      underwent ophthalmologic examination including digital colour fundus photography
      and stereoscopic fluorescein angiography and indocyanine green angiography
      (ICGA). Classification into PCV or CNV was based on ICGA findings, and presence
      or absence of haemorrhagic PED was documented. RESULTS: In total, 138 eyes of 123
      patients were diagnosed with PCV and 152 eyes of 130 patients with CNV. A
      haemorrhagic PED was a significantly more common (P<0.001) presenting feature in
      PCV eyes (63, 45.7%) than CNV eyes (6, 3.9%) (odds ratio (OR) 20.4, 95%
      confidence interval (CI) 8.5-49.4). Age-related maculopathy was found
      significantly more frequently (P<0.001) in the unaffected fellow eye of CNV
      patients (57, 52.8%) than PCV patients (28, 22.8%) (OR 3.2, 95% CI 1.8-5.7).
      CONCLUSIONS: In patients of Chinese ethnicity, a haemorrhagic PED is
      significantly more likely to be the presenting feature of PCV than CNV. Patients
      presenting with this clinical feature should make the clinician suspicious of an
      underlying diagnosis of PCV.

PMID- 19745837
TI  - A role for photoreceptors in retinal oedema and angiogenesis: an additional
      explanation for laser treatment?
AB  - PURPOSE: To investigate the possible roles of retinal photoreceptors in macular
      oedema and retinal angiogenesis with particular reference to the mode of action
      of laser therapy. METHODS: (i) Studies in rats made hypoxic for 2 h by
      administering an oxygen/nitrogen mixture of reduced oxygen content, and growth
      factors determined by RT-PCR, western blotting, and immunohistochemistry.
      Assessment of blood-retinal barrier integrity using fluorescent and electron
      dense tracers. (ii) Studies in pigs with one retina made hypoxic by selective
      embolisation of the retinal capillary circulation with fluorescent microspheres.
      (iii) Assessment of laser therapy in selected cases of retinal neovascularisation
      indicating a role for photoreceptors. RESULTS: In the hypoxic retina, angiogenic
      and vascular permeability factors such as vascular endothelial growth factor
      (VEGF), nitric oxide synthases (NOSs), and insulin-like growth factor-1 are
      upregulated in retinal astrocytes and Muller cells but are also present in large
      amount in the photoreceptors. Hypoxia-inducible factor-1 (HIF-1) is upregulated
      in retinal glial cells but not in the photoreceptors, suggesting that growth
      factors in the photoreceptors may not have been generated there. The tracer dye,
      rhodium isothiocyanate, leaking from an abnormally permeable inner blood-retinal
      barrier in the hypoxic retina accumulates in the photoreceptors. CONCLUSIONS: The
      results indicate that laser treatment of macular oedema or retinal
      neovascularisation may obtain its effect not only by improving oxygen
      availability in the inner retina, but also by reducing the load of
      angiogenic/permeability factors that accumulate in the photoreceptors in
      hypoxic/ischaemic conditions.

PMID- 19745838
TI  - Breastfeeding and association with refractive error in young Singapore Chinese
      children.
AB  - PURPOSE: The objective of this study was to investigate an association between
      spherical refractive error and breastfeeding. METHODS: Strabismus, amblyopia, and
      refractive errors in Singaporean preschoolers (STARS) is a cross-sectional
      population-based study of 3009 Chinese children aged 6-72 months conducted
      between June 2006 and September 2008 in Singapore. Parents were asked about the
      history of breastfeeding in face-to-face interviews. Children without cycloplegia
      or without refraction assessment were excluded. The final sample analysed was
      2639 children (1375 male, 1264 female). RESULTS: Out of those who were breastfed,
      842 (41.3%) were breastfed for more than 3 months and 599 (29.4%) were breastfed
      longer than 6 months. The prevalence of myopia, defined as the spherical
      equivalent refraction of the right eye of at least -0.5 dioptres (D), was 11.3%
      (95% CI (10.1, 12.5)). The mean spherical equivalent refraction of breastfed
      children was 0.12 D higher than that of children who were not breastfed (P
      value=0.03). Breastfeeding, however, was not associated with myopia (adjusted
      OR=0.85; 95% CI (0.62, 1.18)). CONCLUSIONS: The results show that breastfeeding
      is associated with more hyperopic spherical equivalent refraction in young
      Chinese children in Singapore.

PMID- 19745839
TI  - Nocardithiocin, a novel thiopeptide antibiotic, produced by pathogenic Nocardia
      pseudobrasiliensis IFM 0757.
AB  - Nocardithiocin is a novel thiopeptide compound produced by the pathogenic
      Nocardia pseudobrasiliensis strain IFM 0757. It shows a strong activity against
      acid-fast bacilli such as the Mycobacterium and Gordonia species. Nocardithiocin
      was highly active against rifampicin-resistant as well as -sensitive
      Mycobacterium tuberculosis strains, and most of the resistant strains were
      inhibited at concentrations ranging from 0.025 to 1.56 microg ml(-1). The
      structure of the thiopeptide antibiotic containing thiazole, natural and
      unnatural amino acids was elucidated by MS and NMR spectral analyses.

PMID- 19745840
TI  - A matter of choice: the establishment of sister chromatid cohesion.
AB  - Sister chromatid cohesion is the basis for the recognition of chromosomal DNA
      replication products for their bipolar segregation in mitosis. Fundamental to
      sister chromatid cohesion is the ring-shaped cohesin complex, which is loaded
      onto chromosomes long before the initiation of DNA replication and is thought to
      hold replicated sister chromatids together by topological embrace. What happens
      to cohesin when the replication fork approaches, and how cohesin recognizes newly
      synthesized sister chromatids, is poorly understood. The characterization of a
      number of cohesion establishment factors has begun to provide hints as to the
      reactions involved. Cohesin is a member of the evolutionarily conserved family of
      Smc subunit-based protein complexes that contribute to many aspects of chromosome
      biology by mediating long-range DNA interactions. I propose that the
      establishment of cohesion equates to the selective stabilization of those cohesin
      mediated DNA interactions that link sister chromatids in the wake of replication
      forks.

PMID- 19745841
TI  - Role of Varp, a Rab21 exchange factor and TI-VAMP/VAMP7 partner, in neurite
      growth.
AB  - The vesicular soluble N-ethylmaleimide-sensitive factor attachment protein
      receptor (SNARE) tetanus neurotoxin-insensitive vesicle-associated membrane
      protein (TI-VAMP/VAMP7) was previously shown to mediate an exocytic pathway
      involved in neurite growth, but its regulation is still largely unknown. Here we
      show that TI-VAMP interacts with the Vps9 domain and ankyrin-repeat-containing
      protein (Varp), a guanine nucleotide exchange factor (GEF) of the small GTPase
      Rab21, through a specific domain herein called the interacting domain (ID). Varp,
      TI-VAMP and Rab21 co-localize in the perinuclear region of differentiating
      hippocampal neurons and transiently in transport vesicles in the shaft of
      neurites. Silencing the expression of Varp by RNA interference or expressing ID
      or a form of Varp deprived of its Vps9 domain impairs neurite growth.
      Furthermore, the mutant form of Rab21, defective in GTP hydrolysis, enhances
      neurite growth. We conclude that Varp is a positive regulator of neurite growth
      through both its GEF activity and its interaction with TI-VAMP.

PMID- 19745842
TI  - Vesicular stomatitis virus inhibits mitotic progression and triggers cell death.
AB  - Vesicular stomatitis virus (VSV) infects and kills a wide range of cell types;
      however, the mechanisms involved in VSV-mediated cell death are not fully
      understood. Here we show that VSV infection interferes with mitotic progression,
      resulting in cell death. This effect requires the interaction of VSV matrix (M)
      protein with the Rae1-Nup98 complex in mitosis, which is associated with a subset
      of ribonucleoproteins (RNPs). VSV displaced Rae1 from spindle poles, caused
      spindle abnormalities and triggered substantial cell death during metaphase.
      These effects were attenuated in cells infected with VSV expressing a mutant M
      protein that does not bind efficiently to the Rae1-Nup98-RNP complex. In cells
      that progressed to late mitosis, M protein prevented proper nuclear formation and
      chromatin decondensation. VSV is an oncolytic (anti-tumour) agent as it
      preferentially replicates and kills tumour cells. As tumour cells have a high
      mitotic index, VSV-mediated mitotic cell death probably contributes to its
      oncolytic activity.

PMID- 19745844
TI  - One-dimensional single-mode fiber-optic displacement sensors for submillimeter
      measurements.
AB  - We demonstrate the working principle of a one-dimensional intensity-based fiber
      optic displacement sensor. The sensor consists of one receiving fiber, which is
      moved laterally in the optical field emitted by an emitting fiber. It is shown
      numerically that the sensor response is highly linear (nonlinearity error of 0.1
      to 2%) for a wide range of travel (2.24 to 860 microm). The sensor response is
      also simulated experimentally using a highly precise robot, the results of which
      correspond very closely to numerical ones. Linearity, travel, and sensitivity are
      experimentally determined for different gaps between the emitting and the
      receiving fibers (10 microm to 10 mm). A design chart that includes the
      nonlinearity error (0.5% to 2%), the travel (2.78 to 860 microm), the sensitivity
      (0.032 to 0.37 dB/microm), and the gap distance (1 to 10 mm) is finally proposed.

PMID- 19745843
TI  - Expression of chimeric antigen receptors in natural killer cells with a
      regulatory-compliant non-viral method.
AB  - Natural killer (NK) cells hold promise for cancer therapy. NK cytotoxicity can be
      enhanced by expression of chimeric antigen receptors that re-direct specificity
      toward target cells by engaging cell surface molecules expressed on target cells.
      We developed a regulatory-compliant, scalable non-viral approach to engineer NK
      cells to be target-specific based on transfection of mRNA encoding chimeric
      receptors. Transfection of eGFP mRNA into ex vivo expanded NK cells (N=5) or
      purified unstimulated NK cells from peripheral blood (N=4) resulted in good cell
      viability with eGFP expression in 85+/-6% and 86+/-4%, 24 h after transfection,
      respectively. An mRNA encoding a receptor directed against CD19 (anti-CD19-BB-z)
      was also transfected into NK cells efficiently. Ex vivo expanded and purified
      unstimulated NK cells expressing anti-CD19-BB-z exhibited enhanced cytotoxicity
      against CD19(+) target cells resulting in > or =80% lysis of acute lymphoblastic
      leukemia and B-lineage chronic lymphocytic leukemia cells at effector target
      ratios lower than 10:1. The target-specific cytotoxicity for anti-CD19-BB-z mRNA
      transfected NK cells was observed as early as 3 h after transfection and
      persisted for up to 3 days. The method described here should facilitate the
      clinical development of NK-based antigen-targeted immunotherapy for cancer.

PMID- 19745845
TI  - Adaptive watermarking scheme using a gray-level computer generated hologram.
AB  - We present a new adaptive blind watermarking scheme using a gray-level computer
      generated hologram in the discrete wavelet transform domain. By utilizing an
      improved fuzzy clustering technique and human visual system , the watermark can
      be adaptively embedded according to block classification. To keep
      imperceptibility and robustness, a novel iterative embedding algorithm is adopted
      to change the to-be-embedded coefficients. Compared with the standard Fuzzy c
      means (FCM) clustering, the suggested improved FCM (IFCM) converges more quickly
      and can avoid local optimum effectively. The experimental results demonstrate
      that the proposed scheme provides good robustness to withstand different kinds of
      common attack. Compared with other methods, the proposed method has the distinct
      advantage of better robustness to a JPEG compression attack.

PMID- 19745846
TI  - Hybrid silica/polymer long period gratings for wavelength filtering and power
      distribution.
AB  - We report long period grating (LPG) devices based on a hybrid architecture
      incorporating photopatternable fluorinated poly(aryl ether ketone) and silica
      layers for applications in wavelength filtering and power distribution. The
      grating structure was implemented using a periodic corrugation on a thermally
      oxidized silica lower cladding layer, a photopatterned fluorinated polymer ridge
      waveguide, and a similar polymer top cladding. In this design, the corrugated
      silica layer allows a highly stable grating structure, while the fluorinated
      polymer offers a low propagation loss and easy processability. Strong rejection
      bands have been demonstrated in the C+L wavelength band, in good agreement with
      theoretical calculations. The fabricated LPG devices show a thermal dependence of
      1.5 nm/ degrees C. Based on this design, an array of waveguides incorporating
      LPGs has also been fabricated. Distribution of light at the resonance wavelength
      across all the channels from a single input has been demonstrated. These results
      are promising for power distribution in photonic network applications or on-chip
      sensors.

PMID- 19745847
TI  - Ring-coupled Mach-Zehnder interferometer optimized for sensing.
AB  - We demonstrate numerically that the theoretical maximum sensitivity of a ring
      coupled Mach-Zehnder interferometer (MZI) optimized as a sensor is about 30%
      greater than the optimized sensitivity of a conventional single-bus ring sensor
      with an identical ring perimeter and loss. The ring-coupled MZI sensor also
      achieves its greater sensitivity with a 25% lower circulating power, which is
      useful for the suppression of undesirable nonlinear effects.

PMID- 19745848
TI  - Analysis of the imaging method for assessment of the smile of laser diode bars.
AB  - We study imaging systems designed to assess the smile of laser diode bars (LDBs).
      The magnification matrix is derived from the required sampling period and the
      geometries of the LDBs and the charge-coupled device (CCD) array. These image
      forming systems present in-plane pure translation invariance, but in the case of
      anamorphic ones, lack in-plane rotation invariance. It is shown that the smile
      parameters of the image of the LDB are linked with the smile parameters of the
      LDB by simple mathematical expressions. The spatial resolution of such optical
      systems is estimated at approximately 1 microm for a mean wavelength of lambda
      approximately 800 nm. Our results suggest that, with the current state-of-the
      art, the formation of imaging methods for LDB smile assessment can be used to
      assess smile heights > or = 1 microm.

PMID- 19745849
TI  - Performance of an optical packet switch with fixed wavelength converter arrays
      under bursty traffic.
AB  - This paper focuses on the performance of a synchronous time-slotted optical
      packet switch. An optical packet switch with fixed wavelength converter arrays is
      proposed. The proposed node architecture uses shared fixed wavelength converter
      arrays and recirculation fiber delay lines to resolve optical packet collisions.
      To make full use of the fixed wavelength converter arrays and fiber delay lines,
      two control schemes are presented and studied. The packet loss probabilities of
      the proposed node architecture are evaluated in detail by simulation experiments.

PMID- 19745850
TI  - Fourier transform pupil functions for modifying the depth of focus of optical
      imaging systems.
AB  - We use a Fourier transform approach to design pupil functions that modify the
      axial depth of focus for an optical system. We extend previous research in
      several ways. We first extend the depth of focus to 4 cm for a 38 cm focal length
      lens. We show that the transverse size of the focused beam is the same as for an
      open pupil. We then multiply the pupil function by a circular harmonic window
      function. The entire depth of focus is now characterized by a vortex beam.
      Finally we multiply our original pupil function by an edge-enhancing window
      function. Now the pupil function produces two sharp focus spots at the locations
      corresponding to the edges of the rectangle function.

PMID- 19745851
TI  - Resonant-wavelength tuning of a nanocavity by subnanometer control of a two
      dimensional silicon-based photonic crystal slab structure.
AB  - We demonstrate fine tuning of the resonant wavelength of a nanocavity in a two
      dimensional silicon-based photonic crystal slab structure by subnanometer control
      of the airhole diameter and slab thickness. Theoretical investigation shows that
      the resonant wavelength depends linearly on the latter two parameters. To
      experimentally demonstrate the fine tuning of the resonant wavelength, we control
      these parameters through chemical processes. The resonant-wavelength shift is
      tuned to 3.25 and 0.36 nm by use of two oxidizing processes. The latter shift,
      which corresponds to a 0.14 nm thick silicon layer, is considerably smaller than
      shifts achieved in previous studies.

PMID- 19745852
TI  - On the modal characteristics of surface plasmon polaritons at a metal-Bragg
      interface at optical frequencies.
AB  - A detailed mathematical analysis along with a theoretical model for the modes
      supported at the interface of a metal and periodically stratified medium (Bragg
      structure) is presented. The modes that are supported at the interface of a
      plasmon active metal (such as gold) and a Bragg structure are commonly known as
      surface plasmon-Bragg modes. We found that these modes have effective indices
      lower than any of the material indices of the layers comprising the Bragg
      structure, and they are highly dispersive when compared to the conventional
      surface plasmon modes that are supported at the metal and dielectric interface.
      The plausible physical explanation behind the strong dispersive behavior of the
      surface plasmon-Bragg mode is provided. Finally, the comparison of dissipation
      loss for the surface plasmon-Bragg modes is investigated and it has been shown
      that there is more than fivefold enhancement in the magnitude of propagation
      lengths as compared to the conventional surface plasmon mode.

PMID- 19745853
TI  - Resolving fringe ambiguities of a wide-field Michelson interferometer using
      visibility measurements of a noncollimated laser beam.
AB  - An actively stabilized interferometer with a constant optical path difference is
      a key element in long-term astronomical observation, and resolving interference
      fringe ambiguities is important to produce high-precision results for the long
      term. We report a simple and reliable method of resolving fringe ambiguities of a
      wide-field Michelson interferometer by measuring the interference visibility of a
      noncollimated single-frequency laser beam. Theoretical analysis shows that the
      interference visibility is sensitive to a subfringe phase shift, and a wide range
      of beam arrangements is suitable for real implementation. In an experimental
      demonstration, a Michelson interferometer has an optical path difference of 7 mm
      and a converging monitoring beam has a numerical aperture of 0.045 with an
      incidental angle of 17 degrees. The resolution of visibility measurements
      corresponds to approximately 1/16 fringe in the interferometer phase shift. The
      fringe ambiguity-free region is extended over a range of approximately 100
      fringes.

PMID- 19745854
TI  - Crossed-beam intermodulated fluorescence spectroscopy as a spatially resolved
      temperature diagnostic for supersonic nozzles.
AB  - A variant of laser saturation spectroscopy has been applied to the determination
      of spatially resolved temperature in low-pressure supersonic flows. By
      copropagating a pump and probe beam with a small crossing angle, the full Doppler
      profile is retained, but the signal is limited to the volume where both beams are
      overlapped. The technique was demonstrated on several rovibrational lines of the
      I2X1Sigma(0g+)-->B3Pi(0u+) transition in a Mach 2 Laval nozzle. A temperature of
      146 K+/-1.5 K was extracted from measurements of the I2P(46) 17-1 spectral line
      with a spatial resolution of 2.4 mm3. Application of the technique to the
      turbulent gain medium of a chemical oxygen-iodine laser is discussed.

PMID- 19745855
TI  - Tellurium-enhanced nonresonant third-order optical nonlinearity in a
      germanosilicate optical fiber.
AB  - A tellurium-doped germanosilicate optical fiber was developed by modified
      chemical vapor deposition and solution doping techniques. Using the continuous
      wave self-phase modulation method, the nonresonant nonlinear refractive index,
      n2, was measured to be 5.52 x 10(-20) m2/W, which is 2 to 3 times that of the
      undoped germanosilicate glass fiber. Polyhedron structures TeO3 and TeO4 with
      GeO4 and SiO4 are believed responsible for lower phonon energy, more nonbridging
      oxygens, and a larger hyperpolarization, leading to the observed higher
      nonresonant optical nonlinearity.

PMID- 19745856
TI  - Panorama of dual-mirror aplanats for maximum concentration.
AB  - Aplanats were recently analyzed for the first time as maximum-performance light
      transfer systems with radiative transfer approaching the thermodynamic limit. We
      present a fundamental categorization scheme that appears to subsume the full
      spectrum of aplanatic designs, illustrated for far-field dual-mirror
      concentrators and motivated by high-irradiance solar applications.

PMID- 19745857
TI  - Performance, structure, and stability of SiC/Al multilayer films for extreme
      ultraviolet applications.
AB  - We report on the performance, structure and stability of periodic multilayer
      films containing silicon carbide (SiC) and aluminum (Al) layers designed for use
      as reflective coatings in the extreme ultraviolet (EUV). We find that SiC/Al
      multilayers prepared by magnetron sputtering have low stress, good temporal and
      thermal stability, and provide good performance in the EUV, particularly for
      applications requiring a narrow spectral bandpass, such as monochromatic solar
      imaging. Transmission electron microscopy reveals amorphous SiC layers and
      polycrystalline Al layers having a strong <111> texture, and relatively large
      roughness associated with the Al crystallites. Fits to EUV reflectance
      measurements also indicate large interface widths, consistent with the electron
      microscopy results. SiC/Al multilayers deposited by reactive sputtering with
      nitrogen comprise Al layers that are nearly amorphous and considerably smoother
      than films deposited nonreactively, but no improvements in EUV reflectance were
      obtained.

PMID- 19745858
TI  - Design and fabrication of white light emitting diodes with an omnidirectional
      reflector.
AB  - This study investigates white light emitting diodes (LEDs), packaged with an
      omnidirectional reflector (ODR) and UV LED of 378 nm. The current work designs an
      ODR to solve the problems of UV leak and low phosphors conversion efficiency with
      a thin film structure of S/(HLH)n/air modified from a quarter-wave stack. Since
      an ODR is a perfect dielectric mirror for UV light, the UV leak can be eliminated
      and recycled to enhance phosphors conversion efficiency. By measuring the
      emission spectrum of a white LED with an ODR, the orientation distribution of the
      color properties, and the radiation power, the current study did not detect any
      UV leak. The average luminous intensity enhancement is 15%.

PMID- 19745859
TI  - Error decomposition and estimation of inherent optical properties.
AB  - We describe a methodology to quantify and separate the errors of inherent optical
      properties (IOPs) derived from ocean-color model inversion. Their total error is
      decomposed into three different sources, namely, model approximations and
      inversion, sensor noise, and atmospheric correction. Prior information on
      plausible ranges of observation, sensor noise, and inversion goodness-of-fit are
      employed to derive the posterior probability distribution of the IOPs. The
      relative contribution of each error component to the total error budget of the
      IOPs, all being of stochastic nature, is then quantified. The method is validated
      with the International Ocean Colour Coordinating Group (IOCCG) data set and the
      NASA bio-Optical Marine Algorithm Data set (NOMAD). The derived errors are close
      to the known values with correlation coefficients of 60-90% and 67-90% for IOCCG
      and NOMAD data sets, respectively. Model-induced errors inherent to the derived
      IOPs are between 10% and 57% of the total error, whereas atmospheric-induced
      errors are in general above 43% and up to 90% for both data sets. The proposed
      method is applied to synthesized and in situ measured populations of IOPs. The
      mean relative errors of the derived values are between 2% and 20%. A specific
      error table to the Medium Resolution Imaging Spectrometer (MERIS) sensor is
      constructed. It serves as a benchmark to evaluate the performance of the
      atmospheric correction method and to compute atmospheric-induced errors. Our
      method has a better performance and is more appropriate to estimate actual errors
      of ocean-color derived products than the previously suggested methods. Moreover,
      it is generic and can be applied to quantify the error of any derived
      biogeophysical parameter regardless of the used derivation.

PMID- 19745860
TI  - Monolithic achromatic nulling interference coronagraph: design and performance.
AB  - We present the design of the monolithic achromatic nulling interference
      coronagraph (MANIC), a nulling interferometer consisting of optically contacted
      prisms and a symmetric beam splitter. The optic is designed to enable the direct
      detection of nearby Jupiter-like exoplanets, and may be extended to enable Earth
      like system detection. The monolithic nature of the optic improves on the current
      state-of-the-art in nulling interferometers by providing built-in alignment and
      stability, as well as a reduction in size and mass. These qualities make the
      MANIC extremely robust and simple to integrate, and an excellent candidate for
      space-based applications.

PMID- 19745861
TI  - Quetelet's fringes due to scattering by small spheres just above a reflecting
      surface.
AB  - In various everyday situations, a characteristic interference pattern can be
      observed on water surfaces. This pattern can be divided into two overlapping
      components: a corona and a system of Quetelet's rings, often with only a section
      of these visible in the form of fringes. We attribute this phenomenon to thin
      films of small spheres located just above the reflecting water surface. Due to
      differences in the optical arrangement, explanatory models applicable for
      conventionally produced Quetelet's rings are not transferable. We present a
      compatible mathematical model and some obvious analogies in order to explain the
      occurrence and properties of this phenomenon.

PMID- 19745862
TI  - Accurate cross-sectional stress profiling of optical fibers.
AB  - A novel technique for determining two-dimensional, cross-sectional stress
      distributions in optical fibers and fiber-based devices is presented. Use of the
      Brace-Kohler compensator technique and a polarization microscope for the
      measurement of retardation due to stress-induced birefringence is described,
      along with the tomographic reconstruction process for the determination of
      stress. Measurements are performed on Corning SMF-28 fiber in an unperturbed
      section, a section near a cleaved end-face, and a section exposed to CO2 laser
      radiation. Cross-sectional stress distributions are presented. Stress relaxation
      is quantified in the cleaved fiber and the fiber exposed to CO2 laser radiation.

PMID- 19745863
TI  - Spectroscopic ellipsometry analysis of silicon nanotips obtained by electron
      cyclotron resonance plasma etching.
AB  - Silicon nanotips fabricated by electron cyclotron resonance plasma etching of
      silicon wafers are studied by spectroscopic ellipsometry. The structure of the
      nanotips is composed of columns 100-140 nm wide and spaced by about 200 nm.
      Ellipsometry data covering a wide spectral range from the midinfrared to the
      visible are described by modeling the nanotip layer as a graded uniaxial film
      using the Bruggeman effective medium approximation. The ellipsometry data in the
      infrared range reveal two absorption bands at 754 and 955 cm(-1), which cannot be
      resolved with transmittance measurements. These bands indicate that the etching
      process is accompanied with formation of carbonaceous SiC and CH(n) species that
      largely modify the composition of the original crystalline silicon material
      affecting the optical response of the nanotips.

PMID- 19745864
TI  - Swing effect of spatial solitons propagating through Gaussian and triangular
      waveguides.
AB  - We report the behavior of spatial optical solitons propagating through
      inhomogeneous waveguides with Gaussian, single triangular, and double-triangular
      refractive index profiles. In a given Gaussian profile, as the soliton amplitude
      decreases below a certain value, its behavior deviates from that of a
      particlelike soliton. Dependence of the swing period of a spatial soliton in a
      single triangular index profile on its amplitude, eta, is less significant than
      that in a Gaussian profile. We also report the interacting behavior of two
      solitons propagating simultaneously through a waveguide with a double-triangular
      index profile. Furthermore, we present the effects of the solitons' initial phase
      factors and amplitude on their behavior.

PMID- 19745866
TI  - Characterization of the double-interval probability distribution as a tool for
      signal or image recovery.
AB  - The relation between the double-interval probability distribution P(tau, tau')
      and the triple-correlation function is shown. This relation allows us, under
      certain conditions, to obtain the value of the triple correlation of a signal by
      measuring the photoelectron interarrival times. This procedure is useful in
      signal or image recovery.

PMID- 19745865
TI  - Optical dynamical processing: an approach using birefringent pupils.
AB  - A new technique is proposed to perform several image-processing operations with
      the same optical system. Each operation can easily be selected by properly
      loading a birefringent photoelastic plate, which acts as the spatial filter of
      the-system. Thus different pupil transmittance configurations can be achieved,
      each of which is associated with a certain image transformation.

PMID- 19745867
TI  - Object reconstruction from photon-limited centroided data of randomly translating
      images.
AB  - Centroiding is investigated as a simple and computationally fast technique of
      object reconstruction, at low light level, from randomly translating images. A
      relationship between the spectrum of the average N-photon centroided frame and
      the object spectrum is presented as well as an algorithm for retrieving the phase
      in the case of one-dimensional objects. Computer-simulated data are used to test
      the relationship and the reconstruction algorithm.

PMID- 19745868
TI  - Demonstration of guided-wave phenomena at extreme-ultraviolet and soft-x-ray
      wavelengths.
AB  - We report an explicit demonstration of classical guided-wave propagation at XUV
      and soft-x-ray wavelengths. Experiments were performed using narrow-band
      synchrotron radiation at 5, 20.8, 21, and 30 nm. Free-standing gold transmission
      gratings served as waveguide structures. These structures had a 300-nm grating
      period with waveguide channel widths as small as 100 nm and were as thick as 700
      nm in the direction of guided-wave transmission. Guided-wave phenomena were
      manifest in strongly asymmetric diffraction patterns resulting from the angular
      tilt of the transmission-grating normal from the incident-beam direction.

PMID- 19745869
TI  - Photon lifetime within a droplet: temporal determination of elastic and
      stimulated Raman scattering.
AB  - Time profiles of the elastically scattered and stimulated Raman scattered
      radiation from single ethanol droplets illuminated by 100-psec mode-locked pulses
      were measured with a streak camera. The Q factor of the droplet, which acts as an
      optical cavity, was deduced from the decay time of the internally trapped
      radiation. Based on the intensity dependence of time profiles, it is also deduced
      that the photon lifetime is limited by the depletion of the internal intensity in
      generating nonlinear-optical radiation.

PMID- 19745870
TI  - Propagation of laser breakdown and detonation waves in transparent droplets.
AB  - A computer model is used to study recent experiments investigating laser-induced
      plasma formation and explosion of single liquid aerosol droplets. The model
      accounts for the formation and evolution of the plasma and the resulting fluid
      flow; it does not account for the initial breakdown. The model shows all the
      qualitative features of the experiment, including laser-supported detonation
      waves, which at high laser intensities rapidly convert the whole droplet into a
      plasma. In addition, quantitative agreement with measured velocities has been
      obtained to within approximately 50%.

PMID- 19745871
TI  - Coherent effects in pump-probe spectroscopy of excitons.
AB  - Femtosecond measurements of coherent effects arising from exciton bleaching in
      bulk GaAs are reported. This phenomenon, which is characterized by spectral
      oscillatory structures, is general and appears whenever the temporal resolution
      is shorter than the material coherence time. This is shown to be a manifestation
      of the uncertainty relation in time-resolved spectroscopy.

PMID- 19745872
TI  - Test of a model of efficient second-harmonic generation in glass optical fibers.
AB  - To test a model recently proposed to account for the observation of efficient
      second-harmonic generation in glass fibers, we have applied a strong dc electric
      field to the glass preform from which the fibers were drawn. We find that at most
      a temporary x(2) is induced, with a lifetime of a few minutes.

PMID- 19745873
TI  - Tunable holographic second-harmonic generators in high-birefringence optical
      fibers.
AB  - The formation of efficient holographic second-harmonic generators in high
      birefringence phosphorus-doped germanosilicate fibers is reported. The influence
      of optical polarization on the nonlinear writing and read-out processes is
      explored. Fiber birefringence permits phase-matched second-harmonic conversion at
      wavelengths within +/-125 cm(-1) (+/-14 nm) of the writing wavelength (1.064
      microm).

PMID- 19745874
TI  - Importance of self-phase modulation for amplitude- and phase-modulated coherent
      optical transmission systems: a comparison.
AB  - We demonstrate that the amount of self-phase modulation in a coherent optical
      transmission system grows more slowly for a phase-modulated than for an amplitude
      modulated signal. Signal degradation is discussed in terms of variations in the
      spectral contents of the amplitude and phase modulations, and explicit analytical
      expressions are given for the linear modulation indices of phase and amplitude of
      phase-shift keying coherent transmission systems.

PMID- 19745875
TI  - Dependence of visibility on input polarization in interferometric fiber-optic
      sensors.
AB  - We present an analysis of the effects of input polarization on the output fringe
      visibility of two-beam interferometric fiber-optic sensors, which predicts the
      existence of interferometer input-polarization eigenmodes for which optimum
      visibility is obtained. Experimental results that verify this are also presented.

PMID- 19745876
TI  - Acousto-optic matrix-matrix multiplier.
AB  - A new architecture for an optical matrix-matrix multiplier is presented. It is
      based on the beam-modulation and Its parallel structure makes it very fast. Some
      physical limitations are discussed.

PMID- 19745877
TI  - Optical on-the-fly conversion of a modified signed digit into two's complement
      binary number representation.
AB  - An optical carry-free technique is introduced for conversion of a modified signed
      digit (MSD) into two's complement binary number. Using a combination of optical
      polarizing beam splitters and retardation waveplates, the proposed device
      performs this conversion on the fly. The availability of this converter will lead
      to a large speed increase for various proposed optical parallel MSD arithmetic
      processors.

PMID- 19745878
TI  - Spatial light modulator and optical dynamic memory using a 6 x 6 array of self
      electro-optic-effect devices.
AB  - Using a 6 X 6 array of integrated quantum-well self-electro-optic-effect devices,
      we demonstrate an optically addressed spatial light modulator able to convert a
      visible, incoherent image into coherent infrared (IR) light. Depending on the IR
      wavelength used, the output is either a positive, binary-thresholded version of
      the input (bistable mode) or its linear, negative (self-linearized) mode. This
      device can also function as a dynamic bistable memory that can retain its
      internal state without power for times as long as 30 sec.

PMID- 19745879
TI  - Encoding and decoding of femtosecond pulses.
AB  - We demonstrate the spreading of femtosecond optical pulses into picosecond
      duration pseudonoise bursts. Spreading is accomplished by encoding pseudorandom
      binary phase codes onto the optical frequency spectrum. Subsequent decoding of
      the spectral phases restores the original pulse. We propose that frequency-domain
      encoding and decoding of coherent ultrashort pulses could form the basis for a
      rapidly reconfigurable, code-division multiple-access optical telecommunications
      network.

PMID- 19745880
TI  - Carrier-induced refractive-index-change in quantum-well lasers.
AB  - We investigated the loaded gain and the carrier-induced refractive-index change
      in quantum-well lasers. A quantum-well laser is found typically to have a higher
      gain and a smaller refractive-index change than a conventional diode laser. We
      also found that the gain and the refractive-index change for these two types of
      semiconductor lasers saturate similarly, with the refractive index being a much
      weaker function of laser intensity.

PMID- 19745881
TI  - Fiber-bundle coupled, diode end-pumped Nd:YAG laser.
AB  - The output of seven laser-diode arrays, combined by a bundle of seven optical
      fibers, was used to end pump a Nd:YAG solid-state laser. Under a rated operation
      of 1 A/diode, maximum TEM(00) single-mode output power of 660 mW was obtained
      with 4.4% total electrical-to-optical conversion efficiency.

PMID- 19745882
TI  - Long-pulse generation with a stable-relaxation-oscillation Nd:YLF laser.
AB  - A simple technique for long-pulse (0.2-2 microsec) generation with neodymium
      lasers has been demonstrated. Under the proper conditions, a normal-mode
      oscillator, operated in a single transverse mode, produces well-defined
      relaxation oscillations from which a single subpulse can be isolated for
      amplification. The characteristic subpulse temporal profile is ideal for
      saturated amplification without pulse shortening. Data are presented for a Nd:YLF
      system consisting of an oscillator followed by a 64-mm-long amplifier. Pulse
      energies in excess of 100 mJ were achieved with a small-signal gain of 630.

PMID- 19745883
TI  - Dynamically stable 0 degrees phase mode operation of a grating-surface-emitting
      diode-laser array.
AB  - A coherent grating-surface-emitting diode-laser array has demonstrated
      dynamically stable operation in the 0 degrees phase mode. The array was operated
      under pulsed conditions, had a peak power output of 44 mW and a large central
      lobe on axis in the far field, and exhibited single-mode spectral output with
      better than 18-dB side-mode rejection.

PMID- 19745884
TI  - Self-protecting semiconductor optical limiters.
AB  - We present a detailed characterization of passive, picosecond optical-power
      limiting devices using tightly focused beams in thick semiconductor samples. This
      study of limiting in ZnSe with 30-psec, 532-nm pulses shows that the resulting
      internal self-action (two-photon absorption plus free-carrier self-defocusing)
      protects the bulk material from optical damage. Simple scaling relations were
      determined from our results that link the limiting energy and the dynamic range
      to the focusing geometry and sample dimensions. These relations were used to
      design a monolithic optical limiter, optimized to have maximum dynamic range and
      minimum limiting energy. This device limits at an input energy of 10 nJ (300 W)
      and has a dynamic range greater than 10(4).

PMID- 19745885
TI  - Photon-echo detection by six-wave mixing.
AB  - Picosecond photon echoes have been generated and detected by using a resonant six
      wave mixing effect. In this process, the induced echo polarization is used to
      drive a four-wave mixing process. The merits of this method compared with other
      techniques of photon-echo detection are discussed. Further examples of
      spectroscopically useful six-wave mixing effects are presented.

PMID- 19745886
TI  - Four-wave mixing in photorefractive crystals with depleted pumps.
AB  - We present an analytical solution and experimental results for four-wave mixing
      in photorefractive crystals with depleted pumps. The approximation that we
      introduce permits a theoretical treatment without numerical computation. The
      measurements, which were performed using a BaTiO3 crystal, are compared with this
      model.

PMID- 19745887
TI  - Photorefractive phase conjugation with orthogonally polarized pumping beams.
AB  - We solve the undepleted-pumps photorefractive four-wave mixing equations for the
      case of orthogonally polarized pump beams. Advantages over the parallel-polarized
      pumps case include the potential for reflectivity enhancement and easy isolation
      of the conjugator from the source. The phase-conjugate reflectivities for both
      the parallel and orthogonally polarized pump beam cases were measured with a
      BaTiO3 crystal, and the results support our theoretical predictions.

PMID- 19745889
TI  - Optical system defect propagation in ABCD systems.
AB  - We describe how optical system defects (tilt/jitter, decenter, and despace)
      propagate through an arbitrary paraxial optical system that can be described by
      an ABCD ray transfer matrix. A pedagogical example is given that demonstrates the
      effect of alignment errors on a typical optical system.

PMID- 19745888
TI  - High photorefractive gain in two-beam coupling with moving fringes in GaAs:Cr
      crystals.
AB  - We report two-beam coupling experiments at 1.06-microm wavelength using
      photorefractive semi-insulating GaAs:Cr in the moving-grating recording mode. The
      steady-state gain coefficient r is measured as a function of fringe spacing
      Lambda, fringe velocity v, applied voltage V0, and incident beam ratio beta. A
      maximum Gamma as high as 6-7 cm(-1) is observed for Lambda approximately 18
      microm, v approximately 1 mm/sec, beta > 10(3), and V(0) approximately 5 kV
      (interelectrode distance 5.8 mm). The agreement with the theory of two-beam
      coupling with moving fringes is discussed. In particular, a set of numerical
      values is obtained for some crystal parameters. Image amplification is
      demonstrated.

PMID- 19745890
TI  - Image coding with binary phase-only filters.
AB  - We show that image-coding filters can be easily constructed using the binary
      phase-only filter and implemented using the Semetex magneto-optic spatial light
      modulator, and experimental results are presented.

PMID- 19745891
TI  - Two-wavelength laser interferometry using superheterodyne detection.
AB  - In two-wavelength interferometry, synthetic wavelengths are generated in order to
      reduce the sensitivity or to extend the range of unambiguity for interferometric
      measurements. Here a novel optoelectronic technique, called superheterodyne
      detection, is presented, which permits measurement of the phase difference of two
      optical frequencies that cannot be resolved by direct optoelectronic heterodyne
      detection. This technique offers the possibility for operation of two-wavelength
      interferometry in real time with arbitrary synthetic wavelengths from micrometers
      to meters in length. Preliminary experimental results are reported. An optical
      arrangement for absolute range-finding applications using tunable-laser sources
      (e.g., semiconductor lasers) is proposed.

PMID- 19745892
TI  - Fabrication and characterization of tuned Gaussian mirrors for the visible and
      the near infrared.
AB  - A thin-film technique has been developed for vacuum fabrication of mirrors with
      Gaussian reflectivity profiles. Samples with diameters from 2 to 8 mm and
      assigned maximum reflectivities for visible or near-IR wavelengths have been made
      and their optical properties evaluated. By properly choosing both the geometry of
      the evaporation source and the masking system, one can obtain quasi-Gaussian or
      super-Gaussian reflectivity profiles.

PMID- 19745893
TI  - Electron-beam-tunable interference filter spatial light modulator.
AB  - A new type of electron-beam-addressed spatial light modulator has been
      demonstrated. It is based on the local tuning of an optothermal nonlinear
      interference filter by the scanned electron beam. Such an e-beam-tunable
      interference filter device should find applications in both display technology
      and optical data processing.

PMID- 19745894
TI  - Real-time photorefractive recording and optical processing for speckle
      velocimetry.
AB  - A photorefractive crystal (Bi(12)GeO(20)) is used to record double-exposure
      speckle patterns produced by Q-switched laser pulses in real-time speckle
      metrology and velocimetry applications. The speckle pattern displacements are
      immediately measured with an optical processor of the type used for measuring
      speckle displacements recorded on photographic film. Operation of the optical
      processor is described and compared with the case of film recording. Observed
      spatial and temporal recording properties of the crystal in this imaging
      configuration are discussed and compared with published results for single
      frequency grating recording in photorefractives. The system is applied to
      measuring velocities of a moving solid object.

PMID- 19745895
TI  - Emission tomography of flame radicals.
AB  - We describe a simple experimental arrangement for emission tomographic
      measurements of radicals in flames. Experimental determinations of two
      dimensional spatially resolved distributions of excited-state CH in atmospheric
      pressure flames are presented. Calibration of the distributions to absolute
      number densities is performed with a Rayleigh scattering technique. Methods for
      simultaneous recording of two to six emission projections and reconstruction from
      very few (two or three) projections are experimentally investigated. The
      potential of emission tomography with high temporal resolution for monitoring,
      e.g., explosions or turbulent flames, is discussed.

PMID- 19745896
TI  - Modifying excitation transfer cross sections with an ac Stark effect.
AB  - We show that it is possible to manipulate electronic energy transfer collision
      cross sections between different atomic species by using a strong electromagnetic
      field close to resonance with a transition between two excited states to modify
      the energy levels (i.e., to create dressed states), which may be placed in or out
      of resonance with populated states (forming a population reservoir) in one of the
      species. We outline an estimate for a transfer cross section for a demonstration
      scheme and show that cross-section enhancements up to the order of 10(3) are
      possible.

PMID- 19745897
TI  - Atomic beam collimation using a laser diode with a self-locking power-buildup
      cavity.
AB  - We have demonstrated a self-locking power-buildup cavity for laser diodes. This
      device requires only a few simple optical elements and can provide a standing
      wave containing as much as 1000 times the power emitted by the laser diode. With
      this device we have obtained an intense standing wave of tunable light that was
      used to collimate a cesium atomic beam. We have studied the power and frequency
      dependence of the beam collimation.

PMID- 19745898
TI  - Two-photon-excited fluorescence spectroscopy of atomic fluorine at 170 nm.
AB  - We report what is to our knowledge the first two-photon-excited fluorescence
      spectroscopy of atomic fluorine. A doubled dye laser at 286 nm is Raman shifted
      in H(2) to 170 nm (sixth anti-Stokes order) to excite ground-state (2)P degrees
      (J) fluorine atoms to the (2)D degrees (J) level. The fluorine atoms are detected
      by one of two methods: observing the fluorescence decay to the (2)P(J) level or
      observing F(+) production through the absorption of an additional photo by the
      excited atoms. We have measured relative two-photon absorption cross sections to
      and the radiative lifetimes of the (2)D degrees (J) states.

PMID- 19745899
TI  - Saturation of green absorption in titanium-doped sapphire laser crystals.
AB  - Saturation of the pump-band absorption in Ti:sapphire has been observed by using
      10-nsec, pi-polarized pulses of 532 nm with fluences up to 4 J/cm(2). A Frantz
      Nodvik method was used for fitting the data and determining the saturation
      fluence (7.6 J/cm(2)) and the absorption cross section (4.9 x 10(-20)cm(2)) at
      532 nm. The peak absorption cross section was calculated to be 6.4 x 10(-20)
      cm(2) at 490 nm. This value is in reasonably good agreement with other
      determination methods.

PMID- 19745900
TI  - Average intensity and contrast of light amplified by a partially homogeneously
      broadened, slightly saturated laser amplifier with stochastic gain distributions.
AB  - We evaluate the average intensity and contrast of the output of a laser amplifier
      in which stochastic gain distributions exist. This situation occurs when
      turbulence flows are developed in a gas- or liquid-laser amplifier. The gain
      medium is assumed to be partially homogeneously broadened and slightly saturated
      and to consist of two-level atoms. In our computations, a plane wave is
      propagated through the gain medium with weak turbulences, under the assumption
      that the size of the first Fresnel zone is much smaller than the characteristic
      length of turbulences.

PMID- 19745901
TI  - Thermal lensing measurement and compensation in a continuous-wave mode-locked
      Nd:YLF laser.
AB  - Thermal lensing effects in a cw-pumped Nd:YLF rod have been characterized,
      permitting the optimization of the laser resonator. In the mode-locking regime, a
      well-designed system generates an average output power similar to that of a
      typical Nd:YAG laser with, however, an increased stability and pulse durations
      that are significantly shorter.

PMID- 19745902
TI  - Metal-clad waveguides for Pb-salt diode lasers.
AB  - Pb-salt waveguides with a metal-clad layer are discussed. It is shown that for TE
      modes one can assume that E(y) = 0 at the metal-semiconductor boundary, while for
      TM modes the complex formalism should be used. It is also shown that lasers with
      a metal-clad waveguide should have only a small increase in their threshold
      current while operating in a TE mode and that they should operate in a TE mode
      since their TM modes generally have high threshold current.

PMID- 19745903
TI  - Unidirectional device for a ring laser using an acousto-optic modulator.
AB  - The behavior of the first-order diffracted beam of an acousto-optic modulator is
      investigated under rotation of the acousto-optic crystal about an axis
      perpendicular to the plane of the incident and diffracted beams. It is found that
      the diffraction efficiency as a function of this rotation is not symmetric about
      the Bragg angle of incidence. A unidirectional device for a ring dye laser that
      uses this effect is demonstrated.

PMID- 19745905
TI  - 2.0 J Ti:sapphire laser oscillator.

PMID- 19745904
TI  - 12.5-W continuous-wave monolithic laser-diode arrays.
AB  - Continuous-wave output power levels of 12.5 W from one facet and power-conversion
      efficiencies as high as 42% have been obtained from a 1-cm monolithic AlGaAs
      laser array. The array consists of twenty 10-stripe lasers.

PMID- 19745906
TI  - Acousto-optic mode-locked soliton laser.
AB  - An acousto-optic modulator has been used to actively mode lock a KCl:Tl degrees
      (1) color-center laser at 1.5 microm. The color-center laser is capable of
      generating transform-limited pulses as short as 6 psec with 2-W cw pump power.
      Based on this actively mode-locked KCl:Tl degrees (1) laser a stable soliton
      laser has been operated, with performance similar to that of the synchronously
      pumped soliton laser.

PMID- 19745907
TI  - Temporal and spatial modulation in laser-pulse propagation.
AB  - An intense laser pulse that is nearly resonant with an atomic transition and that
      can initially be described as smooth and nearly adiabatic can acquire significant
      temporal and spatial modulation as the result of propagation through an atomic
      vapor. Computer calculations demonstrate that the temporal modulation is a result
      of enhancement, under propagation, of the initially small nonadiabatic portion of
      the transient nonlinear atomic response. The transient nonlinear atomic response
      varies with the field strength so that the transverse variation in field strength
      results in a spatial modulation, known as conical emission.

PMID- 19745908
TI  - Optical second-harmonic generation as a surface probe for noncentrosymmetric
      media.

PMID- 19745909
TI  - Fission of optical solitons induced by stimulated Raman effect.

PMID- 19745911
TI  - Transverse offset data processing for evaluating Petermann's ;;strange'' mode
      field diameter: a comparison of three methods.

PMID- 19745910
TI  - Tapered-fiber interferometric wavelength response: the achromatic fringe.

PMID- 19745912
TI  - Polarization-desensitized liquid-crystal overlay optical-fiber modulator.

PMID- 19745913
TI  - Optical-fiber phase modulator with enhanced modulation efficiency.
AB  - A novel piezoelectrically driven optical-fiber phase modulator is described. The
      modulator has low thermal drift and minimum polarization modulation and is immune
      to variations in the characteristics of the piezoelectric transducer. The
      theoretical model of the modulator accurately predicts the experimental
      performance, showing a phase-modulation enhancement over a wraparound fiber
      modulator at resonance.

PMID- 19745914
TI  - Porous optical fibers for high-sensitivity ammonia-vapor sensors.
AB  - A new porous glass optical fiber has been developed for use as a sensor for the
      detection of ammonia vapors at low concentrations. The porous structure that
      remains after selective heat treatment, phase separation, and chemical leaching
      of a borosilicate glass imparts a high surface area to the fiber core. Ammonia
      vapors permeating into the porous zone, which is pretreated with a reversible pH
      dye indicator, produce a spectral change in transmission. The resulting pH change
      is measured by in-line optical absorbance and is proportional to the ambient
      ammonia concentration. Ammonia-vapor concentrations as low as 0.7 part in 10(6)
      have been detected.

PMID- 19745915
TI  - Effects of the second harmonic and the duty cycle on the scale factor of a fiber
      optic gyroscope with gated two-harmonic phase modulation.
AB  - We show that an electronic servo loop can be closed stably and accurately on a
      fiber-optic gyroscope by using the phase-modulation technique. Using a closed
      loop fiber-optic gyroscope with gated two-harmonic phase modulation, an
      experiment on the linearity was performed; a linearity of approximately 0.5% was
      achieved below 90 degrees /sec. The parameter dependencies of the linearity are
      discussed and theoretical and experimental results given.

PMID- 19745916
TI  - Effect of reflections on the drift characteristics of a fiber-optic passive ring
      resonator gyro.
AB  - We show the effect of reflections at the fiber ends on the drift characteristics
      of a fiber-optic passive ring-resonator gyro. A rotation-detection sensitivity as
      low as 3 x 10(-5) rad/sec (tau = 30 sec) was obtained by reducing the effect of
      reflected lights with an optical phase modulator.

PMID- 19745917
TI  - Relation between the ordinary and extraordinary index profiles of ion-exchanged
      glass waveguides.
AB  - The relation between the ordinary and extraordinary index profiles of ion
      exchanged glass waveguides is investigated on the basis of the stress-optic law
      and the Clausius-Mossotti relation. For K(+) exchange and Ag(+) exchange, the
      experimental results are consistent with our analysis. The values of the
      coefficient that relates the ordinary and extraordinary index profiles are
      presented.

PMID- 19745918
TI  - Nonlinear directional coupler with a diffusive Kerr-type nonlinearity.
AB  - We present numerical results showing the effects of a diffusive Kerr-type
      nonlinearity on the switching characteristics of a nonlinear directional coupler.
      It is found that switching can still occur even when the diffusion length is
      equal to the waveguide separation but that then its threshold increases and
      becomes less pronounced.

PMID- 19745919
TI  - Dynamic response of an all-fiber ring resonator.
AB  - An analysis of the dynamic response of a single-mode all-fiber ring resonator is
      presented in which a time-varying phase shift is induced in the ring by a phase
      modulator. In particular, the deviation of the response from that expected from
      the steady-state analysis is discussed.

PMID- 19745920
TI  - Coupling of polarization-maintaining optical fibers to Ti:LiNbO(3) waveguides
      with angled interfaces.
AB  - Angled interfaces between Ti:LiNbO(3) guided-wave devices and fiber-optic
      pigtails have been used to suppress backreflections. The effect of angled
      interfaces on coupling loss between polarization-maintaining fibers and
      Ti:LiNbO(3) waveguides is investigated. The theory is developed and predicts very
      small increases in coupling loss for modest interface angles (10 deg).
      Experiments confirmed the theoretical coupling angles, and the added loss due to
      angling was measured to be 0.57 dB per interface. A Mach-Zehnder modulator was
      made, with optimized angled-interface geometry, which exhibited no additional
      insertion loss compared with that from similar devices with perpendicular
      interfaces.

PMID- 19745921
TI  - Weak coupling of parallel waveguides: erratum.

PMID- 19745922
TI  - Parallel optical pyramidal image processing.
AB  - Pyramidal processing is a form of multiresolution image processing in which the
      image is decomposed into a sequence of images at different resolutions. Pyramidal
      processing aims to extract and interpret significant features of an image at
      different resolutions. Digital pyramidal image processing, because of the large
      number of convolution- type operations, is time consuming. On the other hand,
      optical pyramidal processors, described here, are preferable in real-time image
      understanding applications because of their ease in performing convolution
      operations. Preliminary experimental results for optical Gaussian and Laplacian
      pyramidal image processing are presented.

PMID- 19745923
TI  - Color-image correlation with a multiwavelength Fresnel holographic filter.
AB  - Theoretical and experimental analyses of color-image pattern recognition using a
      multiwavelength Fresnel holographic filter (FHF) are presented. The FHF technique
      permits a greatly relaxed spatial-filter alignment requirement, use of a white
      light source, negligible color cross talk, and high diffraction efficiency of the
      spatial filter.

PMID- 19745924
TI  - Scalar and vector holographic gratings recorded in a photoanisotropic amorphous
      As(2)S(3) thin film.
AB  - Theoretical explanations of the kinetics of scalar and vector holographic
      gratings are developed, and experimental results are obtained in amorphous
      AS(2)S(3) thin films. The large nonlinear-optical susceptibilities are evaluated
      from experimental data in the vicinity of the fundamental absorption edge, and it
      is found that chi((3))(1111) congruent with 3.2 x 10(-2) esu and
      chi((3))(1122)/chi((3))(1111) congruent with 0.98.

PMID- 19745925
TI  - Electro-optic total internal reflection modulation.
AB  - We report the first observation, to our knowledge, of the electro-optic effect in
      total internal reflection. Light from a He-Ne laser is incident through a high
      index prism upon a KDP crystal to which a pulsed electric field is applied
      through coated-surface electrodes. At the critical angle for total internal
      reflection, a narrow resonance in the modulated reflected light is observed. This
      effect is well described by solving the standard boundary-value problem of
      nonlinear optics.

PMID- 19745926
TI  - Ultrahigh-resolution, wide-field-of-view optical filter for the detection of
      frequency-doubled Nd:YAG radiation.
AB  - We report a simple theoretical model for the calculation of the dependence of
      filter quantum efficiency versus laser pump power in an atomic Rb vapor laser
      excited optical filter. We present the calculations for a 532.4-nm Rb filter that
      can be used to detect the practical and important frequency-doubled Nd:YAG laser.
      The results of these calculations show that the filter's quantum efficiency is
      relatively insensitive to the laser pump power. The laser powers required to pump
      the filter range from 3.6 to 226 mW per square centimeter of filter aperture.

PMID- 19745927
TI  - Emission from ionic cesium fluoride excimers excited by a laser-produced plasma.
AB  - CsF vapor generated in a heat pipe was excited by a laser-produced plasma.
      Temporally integrated spectra and time-resolved fluorescence on the ionic excimer
      transition Cs(2+)F(-) ? Cs(+)F were observed at 185 nm. The pressure dependence
      of the fluorescence is influenced by self-absorption in the CsF vapor. The
      fluorescence is assigned to the Cs(2+)F(-) ((2)Sigma(1/2), B)? Cs(+)F
      ((2)Sigma(1/2),X) transition.

PMID- 19745928
TI  - Intracavity absorption measurements from liquid samples in an Ar(+)-ion laser.
AB  - We present experimental intracavity absorption measurements carried out in a
      commercial Ar(+)-ion laser with a modified resonator. The samples were aqueous
      solutions of Rhodamine 6G. The smallest detectable concentration was 1 x 10(-13)
      mol/L for lambda = 488 nm. This is equivalent to an internal absorbance of 3.5 x
      10(-9). Similar measurements were performed with lambda = 514.5 nm, but time- and
      space-periodic intensity fluctuations, particularly at lower light levels,
      reduced the sensitivity of the absorption detection.

PMID- 19745929
TI  - Atomic-density-dependent losses in an optical trap.
AB  - We have observed that two-body collisions between cold sodium atoms confined
      within a magnetic-molasses optical trap lead to significant atomic-density
      dependent trap losses. Such losses set an upper limit to the product of atomic
      density and confinement time that can be achieved in such a trap.

PMID- 19745930
TI  - Modal coupling in tilted-mirror waveguide lasers and amplifiers.
AB  - Tilted-mirror facets have been introduced as a design alternative to
      antireflection coating for waveguide structures that require low facet
      reflectivity. We show that tilted-mirror facets with finite reflectivity can
      induce significant intermode coupling in semiconductor lasers and optical
      amplifiers. We describe the effect of tilt-induced intermode coupling on the
      cavity modes using a simple model and discuss the implications of our results on
      the design of tilted-mirror integrated-optical lasers and amplifiers.

PMID- 19745931
TI  - Continuous-wave mode-locked Nd:glass laser pumped by a laser diode.
AB  - We have demonstrated a diode-laser-pumped, cw, mode-locked Nd:glass laser
      oscillator. With a 0.5% output coupler the pump threshold for mode-locked
      operation was 22.9 mW. The mode-locked pulse width was shorter than 36.5 psec,
      which was the response time of the fast photodiode and the sampling oscilloscope.
      Diode-laser-pumped mode-locked operation was also extended to Nd:YAG.

PMID- 19745932
TI  - Single-frequency Q-switched operation of a diode-laser-pumped Nd:YAG laser.
AB  - We describe the performance of a single-frequency Q-switched Nd:YAG laser
      operating at 1.06 microm and optically pumped by a 100-mW diode laser. This
      system provides pulses of 6-microJ energy with peak powers greater than 125W at
      40-nsec duration with less than 16-MHz linewidth.

PMID- 19745933
TI  - Optical short-pulse generation using diode lasers with negative optoelectronic
      feedback.
AB  - A new method of optical short-pulse generation using stable diode lasers with
      negative optoelectronic feedback is proposed. Optical pulses with repetition
      rates of several gigahertz can be generated with a calculated pulse width of the
      order of a picosecond, and the required gain-bandwidth product of the feedback
      network is a few tens of gigahertz. This method does not require any external
      modulation signal, and it is not susceptible to critical optical alignment.

PMID- 19745934
TI  - Amplification of 1-nsec pulses in Nd:glass followed by compression to 1 psec.
AB  - We use the grating-compression approach to extend the possibilities of chirped
      pulse amplification. A 50-psec pulse is stretched to 1 nsec before being
      regeneratively amplified in Nd:glass. Subsequent compression to 1 psec allows for
      high-peak-power pulse generation with small nanosecond-type amplifiers.

PMID- 19745935
TI  - Generation of sub-100-fsec pulses tunable near 497 nm from a colliding-pulse mode
      locked ring dye laser.
AB  - A colliding-pulse mode-locked ring dye laser with Coumarin 102 passively mode
      locked by 3,3'-diethyloxacarbocyanine iodide has been developed. Pulses of less
      than 100-fsec duration have been obtained from 493 to 502 nm at a repetition rate
      of 160 MHz. A similar operation has also been obtained with alternative saturable
      absorbers.

PMID- 19745936
TI  - Generation of squeezing in two-photon three-level media.
AB  - We present a fully quantum-mechanical theory of nondegenerate four-wave mixing
      processes in three-level cascades with a two-photon pump. The results are applied
      to the generation of squeezed states of light. We find almost perfect squeezing
      for some strong pump intensities and tunings within the Rabi sidebands. We find
      good broadband squeezing for low pump intensities and tunings outside a small
      region around central tuning. Both cases avoid regions of significant spontaneous
      emission.

PMID- 19745937
TI  - Detection of amplitude modulation with squeezed light for sensitivity beyond the
      shot-noise limit.
AB  - An improvement in precision beyond the limit set by the vacuum-state or zero
      point fluctuations of the electromagnetic field is reported for the detection of
      amplitude modulation encoded on a weak signal beam. The improvement is achieved
      by employing the squeezed light from an optical parametric oscillator to reduce
      the level of fluctuations below the shot-noise limit. An increase in signal-to
      noise ratio of 2.5 dB relative to the shot-noise limit is demonstrated.

PMID- 19745938
TI  - Laser-heating-induced self-phase modulation, phase transition, and bistability in
      nematic liquid crystals.
AB  - A quantitative discussion of the laser-heating-induced self-phase modulation in
      nematic liquid crystals is given. The process of the laser-heating-induced
      nematic-isotropic transition is analyzed. The intrinsic optical bistability due
      to the nematic-isotropic phase transition is observed and analyzed.

PMID- 19745939
TI  - Subharmonic Raman effect in nonlinear mixing.
AB  - Following the recent experiments of Trebino and Rahn [Opt. Lett. 12, 912 (1987)],
      I show on general grounds the existence of the fractional Raman resonances in a
      variety of nonlinear mixing processes in atomic vapors, molecules, and solids. I
      present theoretical models, both classical and quantum, for such resonances.

PMID- 19745940
TI  - Passive one-way aberration correction using four-wave mixing.
AB  - We have demonstrated a passive method for recovering an optical image that has
      been degraded by being passed through a thin phase-aberrating medium. This method
      relies on a point source situated near the object of interest to sample the
      aberration impressed upon the wave front. Degenerate four-wave mixing in
      fluorescein-doped boric acid glass was used to reconstruct the wave front.

PMID- 19745941
TI  - Nonlinear refraction in CS(2) at 10.6 microm.
AB  - The nonlinear refractive index n(2) of CS(2) at 10.6 microm, the value of which
      is a subject of a recent controversy, is measured by an external self-focusing
      method. We found that n(2) = (2.1 +/- 0.7) x 10(-11) esu, similar to the accepted
      value of n(2) in the visible. Self-bending of spatially asymmetric CO(2) laser
      beam in CS(2) due to an ultrafast Kerr effect is observed, and the deduced value
      of n(2) is in agreement with our results.

PMID- 19745942
TI  - Phase cross correlation in the coherent Raman process.
AB  - The coherent anti-Stokes Raman scattering (CARS) process with two different-color
      phase-fluctuating fields was studied experimentally and theoretically. It was
      found that the efficiency of this process depends strongly on the cross
      correlation between the phases of the driving fields. Depending on the detuning
      from Raman resonance, the CARS signal can be either enhanced or suppressed with
      respect to the case of uncorrelated fields.

PMID- 19745943
TI  - Stimulated Raman scattering in micrometer-sized droplets: time-resolved
      measurements.
AB  - Time-resolved measurements of elastic scattering and stimulated Raman scattering
      (SRS) in micrometer-sized water and carbon tetrachloride droplets irradiated with
      a pulsed, frequency-doubled Nd:YAG laser (pulse width 8 nsec, lambda = 532 nm,
      peak intensity ~1 GW cm(-2)) are reported. Elastic scattering of light is
      instantaneous within our measurement error, estimated to be <+/-3 nsec. On the
      other hand, the first Stokes shift in water and multiple-order (through ninth
      order) Stokes shifts in carbon tetrachloride are delayed from the elastically
      scattered light by 5-7 nsec. The delay in SRS is apparently a consequence of
      structure resonances within the droplet, which acts as an optical cavity with
      relatively high Q. Quasi-periodic peaks in SRS spectra of water droplets are
      shown to be associated with elastic-scattering structure resonances having the
      same mode order.

PMID- 19745944
TI  - Time dependence of multiorder stimulated Raman scattering from single droplets.
AB  - An optical multichannel detection technique was used to measure simultaneously
      the time profiles of the input laser pulse and the elastic scattering, as well as
      the time profiles of the spectrally resolved multiorder stimulated Raman
      scattering (SRS), from single droplets. The time delay between the multiorder SRS
      and the input laser pulse is consistent with the generalized four-wave mixing
      process for first-order stimulated Raman growth, starting from spontaneous noise
      or the parametric signal. The presence of an internal plasma associated with
      laser-induced breakdown within a droplet quenches the SRS and increases the
      elastic scattering.

PMID- 19745945
TI  - Nondegenerate two-wave mixing in ruby.
AB  - We demonstrate energy exchange by nondegenerate two-wave mixing in ruby. Our
      results are in agreement with the theory of nondegenerate two-wave mixing when
      the theory is generalized to take into account a complex nonlinear index. Two
      wave mixing gain exceeding the absorption and reflection losses is demonstrated,
      and we show that these experiments provide a simple and accurate method for
      determining the complex nonlinear index, response time, and saturation intensity
      of the medium.

PMID- 19745946
TI  - Real-time parallel optical logic in photorefractive bismuth silicon oxide.
AB  - Fast parallel analog and digital optical computing operations are demonstrated by
      using an interferometric arrangement with photorefractive bismuth silicon oxide.
      Image subtraction, coherent weighted-image addition, exclusive OR/NOT, and OR
      optical gates are achieved by controlling the relative phase shifts of two phase
      conjugate waves generated by degenerate four-wave mixing.

PMID- 19745947
TI  - Coherent optical detection through two-wave mixing in photorefractive materials.
AB  - Photorefractively induced index-of-refraction phase gratings are shown to combine
      coherently the optical fields of a strong pump and a suitably amplitude- or phase
      modulated signal beam in such a way that an apparent amplification of the
      modulating waveform appears as intensity modulation of the transmitted signal and
      pump beam intensities. The source of the signal gain is shown to be the square
      law (intensity) detection of the coherently combined pump and modulated signal
      beams, just as in coherent optical communication systems in which a strong local
      oscillator field is coherently added with a weak optical signal field by a beam
      splitter.

PMID- 19745948
TI  - Temporal behavior of the intensity-dependent absorption in photorefractive
      BaTiO(3).
AB  - We report measurements of response time for the intensity-dependent absorption in
      a single BaTiO(3) crystal under conditions in which no photorefractive effect can
      be observed. The speed of response is found to increase with increasing intensity
      but in a sublinear fashion similar to that observed for photorefractive decay.
      This experiment provides unambiguous evidence for the intensity-dependent
      absorption in BaTiO(3) crystals.

PMID- 19745949
TI  - Preparation of long-coherence-length second-harmonicgenerating optical fibers by
      using mode-locked pulses.
AB  - We have prepared an optical fiber that produces efficient (0.24%) second-harmonic
      conversion by using modelocked 1.064-microm laser pulses along with a harmonic
      seeding beam. The effective coherence length increased to 35 cm as compared with
      only a few centimeters in fibers prepared with mode-locked Q-switched pulses. We
      show that the input bandwidth of the pump pulse imposes a fundamental limit on
      the effective coherence length and that this length can be severely reduced by
      competing nonlinear effects.

PMID- 19745950
TI  - Light-induced erasure of self-organized chi((2)) gratings in optical fibers.
AB  - Self-organized chi((2)) gratings in optical fiber, prepared by irradiating the
      fiber with 1.06-microm light from a Q-switched mode-locked Nd:YAG laser
      simultaneously with its second harmonic, can be erased optically. This is
      accomplished by irradiating the prepared fiber with the 532-nm mode-locked Q
      switched light alone, without the 1.06-microm light, or with intense green or
      blue light from an argon laser. The erasure is reversible, and the fiber can be
      reprepared as before for second-harmonic conversion. The nonexponential time
      dependence of the erasure process can be explained by a model involving charge
      separation during seeding and recombination during erasure.

PMID- 19745951
TI  - Modulation-instability-based fiber interferometer switch near 1.5 microm.
AB  - We demonstrate a modulation-instability-based fiber interferometer switch, an
      ultrafast all-optical fiber switch operating near 1.5-microm wavelength with more
      than 40dB of small-signal gain. Switching is accomplished.by seeding the
      modulation instability in one arm of a Mach-Zehnder interferometer, thus
      destroying its balance. Computer simulations, which include the effects of Raman
      self-frequency shifts, suggest that as much as 74% of the power input to the
      interferometer can be transferred to its (initially nulled) output arm when cw
      pumps are used. Even with an 80% loss at the output analyzer, we have gated 184
      mW of power from a color-center laser using only 4.4 microW from a semiconductor
      laser.

PMID- 19745952
TI  - Open-loop fiber-optic gyroscope using intensity-modulated source and phase
      modulation.
AB  - A simple open-loop approach to a standard fiber-optic gyroscope that uses an
      intensity-modulated source is described. Direct readout of the Sagnac effect in
      an open-loop form is obtained by applying a sinusoidal modulation to the source
      and the phase modulator at the proper frequency, with the modulation depth of the
      source adjusted appropriately. Experimental results show good linearity over a
      wide dynamic range.

PMID- 19745953
TI  - Polarization properties of evanescent couplers.
AB  - While there have been several attempts recently to extend the accuracy of vector
      coupled-mode theory beyond the usual first-order expression for evanescent
      couplers, as yet no analytical method is available for describing the
      polarization properties of couplers with a large core-cladding index jump. Here
      we present a quasi-static approximation for couplers of low V value, where V is
      the usual waveguide parameter.

PMID- 19745954
TI  - Automatic endless polarization control with integrated-optical Ti:LiNbO(3)
      polarization transformers.
AB  - In coherent-optical transmission systems continuous or endless polarization
      matching between the superposed beams must be ensured. We describe a practical
      closed-loop polarization-control system with two integrated-optical retarders
      acting as polarization transformers. They have variable retardations and variable
      eigenmodes, i.e., adjustable birefringence magnitude and orientation as in a
      Babinet-Soleil compensator. In theory, one retarder would be sufficient. However,
      a second device is added to correct nonideal behavior of the first. The intensity
      losses during polarization control are less than 0.15 dB.

PMID- 19745955
TI  - Conditions for the occurrence of k gaps for surface polaritons on gratings.
AB  - We obtain a formula for the change of the reflectivity from a symmetric metallic
      grating due to the excitation of surface polaritons. We find that reflectivity
      measurements at near-normal incidence can show a k gap in the dispersion curves
      of the surface polaritons even when direct coupling between two polaritons at the
      zone boundary is present. We discuss the limit in which this can occur and
      examine the reflectivity surface as the direct coupling is varied. The formula
      permits a simple discussion of the k gaps at 2npi/a for any n.

PMID- 19745956
TI  - Optical-processor architectures for alternating-projection neural networks.
AB  - Optical-processor architectures for various forms of the alternating-projection
      neural network are considered. Required iteration is performed by passive optical
      feedback. No electronics or slow optics (e.g., phase conjugators) are used in the
      feedback path. The processor can be taught a new training vector by viewing it
      only once. If the desired outputs are trained to be either +/-1, then the network
      can be configured to converge in one iteration.

PMID- 19745957
TI  - Degenerate photon echoes: simultaneous storage of multiple optical data.
AB  - It is shown that simultaneous and spatially overlapping multiple photon echoes
      can occur following application of a single optical pulse followed by multiple
      pairs of counterpropagating pulses in various directions-degenerate photon
      echoes. This scheme has been experimentally verified in Pr(3+):LaF(3) for the
      doubly degenerate case. In the small-pulse-area regime, the two echoes are
      observed to be independent with no cross talk between them. From the viewpoint of
      transient optical memory, this enables us to store multiple independent optical
      data in one sample spot and to retrieve any one of them, thereby multiplying the
      memory capacity of the crystal.

PMID- 19745958
TI  - Fully orthogonal optical-code multiplex for broadcasting.
AB  - A novel method of optical-code multiplex transmission from a central location is
      proposed. It has the advantages that the receivers can be configured to any
      channel quickly, the channels have in principle zero cross talk, and the
      bandwidth-expansion factors are less than for other optical-code-division
      multiple access arrangements. The proposed method is based on arrays of
      optoelectronic switching detectors that are at present under development for
      broadband matrix switching.

PMID- 19745959
TI  - Interative blind deconvolution method and its applications.

PMID- 19745960
TI  - Noncontact tension sensing by the photothermoelastic effect.

PMID- 19745961
TI  - Optical heterodyne measurement of the phase retardation of a quarter-wave plate.

PMID- 19745962
TI  - Hyperfine structure of the P(48) line in the 11-3 band of iodine molecules by FM
      saturation spectroscopy at 612 nm.

PMID- 19745963
TI  - Temporally and spatially resolved spectroscopy of laser-induced plasma from a
      droplet.

PMID- 19745964
TI  - Measurement of the Pancharatnam phase for a light beam.

PMID- 19745965
TI  - Proposal for soft-x-ray and XUV lasers in capillary discharges.

PMID- 19745967
TI  - Coupled-wave theory of multiple-stripe semiconductor injection lasers.

PMID- 19745966
TI  - Narrow-linewidth unstable resonator.

PMID- 19745968
TI  - Interferometric measurements of femtosecond group delay in optical components.

PMID- 19745969
TI  - Dual synchronously pumped and synchronously amplified dye lasers.

PMID- 19745970
TI  - Terawatt XeCl discharge laser system.

PMID- 19745971
TI  - Phase conjugation in liquid CS2 by using a pulsed CO2 laser.

PMID- 19745972
TI  - Real-time optical image subtraction using dynamic holographic interference in
      photorefractive media.

PMID- 19745973
TI  - Self-focusing and self-phase modulation in a parabolic graded-index optical
      fiber.

PMID- 19745974
TI  - Generation of permanent optically induced second-order nonlinearities in optical
      fibers by poling.

PMID- 19745976
TI  - Tapered polarizing anisotropic fibers.

PMID- 19745975
TI  - Identification of longitudinal acoustic modes guided in the core region of a
      single-mode optical fiber by Brillouin gain spectra measurements.

PMID- 19745977
TI  - Optical heterodyne method for evaluating the power coupling in the single-mode
      guided-wave Mach-Zehnder interferometer fabricated upon a silicon substrate.

PMID- 19745979
TI  - Beam-propagation method ray equation.

PMID- 19745978
TI  - Improvement of frequency-conversion efficiency in waveguides with rotationally
      twinned layers.

PMID- 19745980
TI  - Gabor's expansion of an optical field in Cauchy elementary beams.

PMID- 19745981
TI  - Wideband speckle spectroscopy based on the shift-and-add method.

PMID- 19745982
TI  - Phase retrieval from experimental far-field speckle data.

PMID- 19745983
TI  - Broadband continuous-wave laser.

PMID- 19745984
TI  - Simultaneous frequency stabilization of three lines in a He-Cd laser.

PMID- 19745986
TI  - Optical pumping of vibrational overtones in KI:CN- infrared lasers.

PMID- 19745985
TI  - Short-coherence-length and high-coupling-efficiency pulsed diode laser for fiber
      optic sensors.

PMID- 19745987
TI  - Temporal reshaping of ultrashort laser pulses after reflection from GaAs at
      Brewster's angle.

PMID- 19745988
TI  - Time-interval statistics through a Laplace-transform method in quasi-elastic
      light-scattering experiments for low-intensity levels.

PMID- 19745990
TI  - Optical parametric oscillation in a beta-barium borate crystal pumped by an XeCl
      excimer laser.

PMID- 19745989
TI  - Intensity-dependent change of polarization of light normally reflected from a
      lang <100> GaAs surface (nonlinear-optical activity on reflection).

PMID- 19745991
TI  - Short-pulse intracavity Raman laser.

PMID- 19745992
TI  - Resolution of discrepancies in measured values of n 2 of CS2 at 10 Mu m.

PMID- 19745994
TI  - Photorefractive spatial light modulation based on enhanced self-diffraction in
      sillenite crystals.

PMID- 19745993
TI  - High-efficiency, energy-scalable, coherent 130-nm source by four-wave mixing in
      Hg vapor.

PMID- 19745995
TI  - Characterization of the photorefractive effect in InP:Fe by using two-wave mixing
      under electric fields.

PMID- 19745996
TI  - Space-charge field in photorefractive materials at large modulation.

PMID- 19745997
TI  - Vector phase conjugation by two-photon-resonant degenerate four-wave mixing.

PMID- 19745998
TI  - Raman amplification in a P2O5-doped optical fiber.

PMID- 19745999
TI  - Second-harmonic generation from quantum noise owing to fifth-order nonlinearity.

PMID- 19746000
TI  - Soliton switching in fiber nonlinear directional couplers.

PMID- 19746001
TI  - Demonstration of soliton transmission over more than 4000 km in fiber with loss
      periodically compensated by Raman gain.

PMID- 19746002
TI  - 5-mm-resolution optical-frequency-domain reflectometry using a coded phase
      reversal modulator.

PMID- 19746004
TI  - Multiple angle-tuned etalon filters for optical channel selection in wavelength
      division multiplexed and optical frequency-division multiplexed direct-detection
      transmission systems.

PMID- 19746003
TI  - Control of power-splitting ratio in asymmetric fused-tapered single-mode fiber
      couplers.

PMID- 19746005
TI  - Statistical treatment of polarization dispersion in single-mode fiber.

PMID- 19746006
TI  - Stationary nonlinear surface waves and their stability in diffusive Kerr media.

PMID- 19746007
TI  - Optical implementation of quadratic associative memory with outer-product
      storage.

PMID- 19746008
TI  - Binary polarization modulator: a simple device for switching light polarization
      between orthogonal states.
AB  - A simple binary polarization modulator is described that periodically switches
      the polarization of a monochromatic light beam between orthogonal linear,
      circular, or elliptical states. It consists of a synchronously rotating disk
      whose planar surface is divided into annuli. Each annulus is segmented by radial
      lines into sectors, and each sector is coated by a thin film that reflects light
      of only one of two orthogonal states. Multiple annuli may be used for multiple
      wavelength operation. Although a single layer is adequate to achieve the desired
      effect, multilayers would be required for higher performance standards.

PMID- 19746009
TI  - NO plume mapping by laser-radar techniques.
AB  - Mapping of NO plumes by using laser-radar techniques has been demonstrated with a
      mobile differential absorption lidar system. The system was equipped with a
      narrow-linewidth Nd:YAG-pumped dye laser that, with doubling and mixing,
      generated pulse energies of 3-5 mJ at 226 nm, with a linewidth of 1pm. This
      permitted range-resolved measurements of NO, with a range of about 500 m. The
      detection limit was estimated to 3 microg/m(3), with an integration interval of
      350 m. Spectroscopic studies on the gamma(0, 0) bandhead near 226.8 nm were
      performed with 1-pm resolution, and the differential absorption cross section was
      determined to be (6.6 +/- 0.6) x 10(-22) m(2), with a wavelength difference of 12
      pm.

PMID- 19746010
TI  - Hemicyanine monolayer orientation studied by second-harmonic generation.
AB  - Using a novel scheme of polarization-dependent excitation and detection, the
      molecular orientation of hemicyanine monolayers has been studied. Wavelength
      dependent measurements of the average tilt angle of molecules within the
      monolayer reveal details of aggregate formation and mobilization of these
      aggregates by addition of diluting agents such as arachidic acid.

PMID- 19746011
TI  - Optical generation of coherent surface acoustics: an optically based probe of
      surface structure and dynamics.
AB  - Above-band-gap picosecond pulses are used to generate holographically high
      frequency, coherent, surface acoustic modes on semiconductor surfaces. Optical
      diffraction from the surface acoustics is in superposition to a free-carrier
      phase grating that acts as an amplifying cross term in the diffraction process.
      The detection limits are of the order of 10(-4) nm for the surface displacement.
      Frequencies up to 2 GHz have been realized, with frequencies >20 GHz possible. A
      quantitative theory for the photothermal coupling has been developed. In
      addition, propagation of the optically generated surface modes has revealed a
      solid-liquid phase transition of the water layer at TiO(2)-H(2)O interfaces.

PMID- 19746012
TI  - Observation of the transient expansion of heated surfaces by picosecond
      photothermal deflection spectroscopy.
AB  - The observation of the picosecond thermal expansion of an absorbing surface after
      a short heating pulse is reported for the first time to my knowledge. The
      measurement was performed on Si by adapting the method of photothermal deflection
      to a pump-probe technique using 1-psec laser pulses. This was achieved by
      separating out a novel deflection effect due to the gradient in the near-surface
      optical constants. The results are compared to a thermo-elastic model, and good
      agreement is found.

PMID- 19746013
TI  - Electro-optical effect of a magnetically biased ferronematic liquid crystal.
AB  - The electro-optical effect of a magnetically biased ferronematic liquid-crystal
      film is investigated by using birefringence measurements. When a magnetic field
      is applied, the threshold voltage of the Freedericksz transition no longer
      exists. The dependence of the birefringence on the magnetic field strength in the
      low field regime is presented. A theory that accounts for the results is given.

PMID- 19746014
TI  - High-sensitivity FM spectroscopy with a lead-salt diode laser.
AB  - We report the demonstration of near-quantum-noise-limited sensitivity with a lead
      salt diode laser using FM spectroscopy and high-speed sweep integration. Using
      both single-tone and two-tone techniques, we demonstrated an absorption
      sensitivity of ~2 x 10(-7) in a 2.44-Hz bandwidth from a Doppler-broadened NO
      line at 1856.5 cm(-1). The sensitivity in our experiments was limited by laser
      excess noise, which was about four times the expected quantum-noise level.

PMID- 19746015
TI  - Spatial averaging and multiplex coherent anti-Stokes Raman scattering temperature
      measurement error.
AB  - We discuss the effect of spatial averaging within the probe volume on multiplex
      coherent anti-Stokes Raman scattering temperature measurements. A numerical
      simulation and an experimental verification on a small laminar flame burner were
      performed. Appreciable measurement errors can be made in reactive laminar or
      turbulent media with large gradients. The errors, which are caused by biasing in
      favor of cold gases, increase with the temperature difference.

PMID- 19746016
TI  - Alignment-insensitive technique for wideband tuning of an unmodified
      semiconductor laser.
AB  - Using simple optical components and an unmodified commercial semiconductor laser,
      a frequency-selective self-aligning optical-feedback technique has been devised
      that allows a semiconductor laser to be tuned to and scanned about any optical
      frequency within the laser gain curve. This technique employs a graded-index rod
      lens cat's eye and an intracavity etalon.

PMID- 19746017
TI  - Multielement laser-diode linewidth theory.
AB  - A simple formula is presented for the linewidth-power product of multielement
      laser diodes, under the condition that the active elements are submitted to the
      same field. The theory is particularly applicable to laser diodes incorporating
      two thin active layers of different composition. Such diodes can be modeled by
      two active conductances in parallel with a linear admittance. If the injected
      current exhibits full shot noise, the laser linewidth is given by the same
      expression as for a single active element, except that alpha and alpha(2) must be
      replaced by their average values weighted by the injected bias currents, where
      alpha denotes the phase-amplitude coupling factor. The same result is applicable
      to conventional index-guided laser diodes.

PMID- 19746018
TI  - Single-frequency output from a broadband-tunable external fiber-cavity laser.
AB  - Single-frequency operation is demonstrated by using a semiconductor laser coupled
      to a tunable fiber-optic reflective filter. This external fiber-cavity laser is
      stepwise tunable over a 66-nm range centered around 1300 nm. Short-term laser
      linewidths are measured to be less than 50 kHz.

PMID- 19746020
TI  - Wavelength optimization and power dependence of optically controlled modulation
      in InGaAsP/InP.
AB  - We investigate wavelength and power dependence of optically controlled
      transmission modulation based on dynamic band filling in InGaAsP (lambda(g) = 1.3
      microm). A maximum modulation depth of 42% is observed at a 1280-nm wavelength
      for 5-mW control power. The modulation depth slightly decreases with increasing
      test power. A theoretical analysis based on carrier rate equations and direct
      electronic transitions between parabolic bands provides a good description of the
      experiments.

PMID- 19746019
TI  - High-irradiance 248-nm laser system.
AB  - A laser system that routinely generates irradiances of 8 x 10(17) W cm(-2) is
      described. Pulses from a mode-locked visible dye laser are heterodyned to 248 nm
      and amplified in two KrF amplifiers. Output is 25-30 mJ in a 700-fsec pulse that
      can be focused to 5 microm(2).

PMID- 19746021
TI  - Real-time measurement of the spatial profile of a pulsed laser by photothermal
      spectroscopy.
AB  - A new method for the measurement of the spatial profile of a pulsed laser is
      demonstrated. The method is based on the photothermal deflection technique. The
      spatial profile of a single pulse can be measured in real time.

PMID- 19746022
TI  - Broadband ultrafast pulse generation from synchronously pumped dye lasers.
AB  - Broadband (up to 70-nm) femtosecond to picosecond laser pulses are generated from
      synchronously pumped dye lasers. We demonstrate that such well-collimated
      broadband laser pulses can facilitate pump-and-probe experiments by measuring the
      evolution of the transmission spectrum of a Schott RG830 doped glass after being
      pumped by 1.4-psec, 532-nm pulses.

PMID- 19746023
TI  - Phase-sensitive single-pulse autocorrelator for ultrashort laser pulses.
AB  - A new single-shot phase-sensitive autocorrelator for picosecond and femtosecond
      measurements is presented. The experimental results show that this device is
      suitable for the study of chirp in single pulses.

PMID- 19746024
TI  - 29-fsec pulse generation from a linear-cavity synchronously pumped dye laser.
AB  - 29-fsec optical pulses at a center wavelength of 615 nm have been generated from
      a linear-cavity synchronously pumped dye laser without using the colliding-pulse
      mode-locking technique. The laser consists of two dye jets (a gain jet and a
      saturable absorber jet) and a sequence of four Brewster-angled prisms. Kiton Red
      S is used as the laser dye instead of the conventional Rhodamine 6G.

PMID- 19746025
TI  - Interference pattern of the supercontinuum generated by self-phase modulation.
AB  - We compute the interference pattern generated by a plane-wave self-phase
      modulated ultrafast pulse. For high intensities, the presence of the amplitude
      phase time shift in this signal generates fringe position shifts. We also compute
      the Fourier transform of the interferometric intensity distribution and relate
      its range to the functions that determine the supercontinuum spectral extents and
      frequency shift.

PMID- 19746026
TI  - Pulse compression of an induced-phase-modulated weak signal.
AB  - We examine the possibility that the first stage in the pulse compression of a
      weak pulse can be achieved through its induced phase modulation by a strong pump.
      The compression ratio for the fiber-and-grating compressor for a weak probe in
      the presence of a pump is computed. Walk-off effects between the probe and the
      pump are incorporated into the calculation.

PMID- 19746027
TI  - Effect of linear absorption on self-focusing.
AB  - We report the effect of linear absorption on self-focusing. Our experimental
      results show that power loss due to linear absorption before focus is responsible
      for the increase in the threshold power for self-focusing and that the critical
      power is independent of the linear absorption.

PMID- 19746028
TI  - Observation of high-order degenerate wave mixing in BaTiO(3).
AB  - We report for the first time to our knowledge some phenomena of high-order
      degenerate wave mixing observed in a BaTiO(3) crystal when self-pumped phase
      conjugation occurs. Applications of these phenomena are discussed.

PMID- 19746029
TI  - Amplified reflection through anisotropic four-wave mixing in BaTiO(3).
AB  - We have demonstrated cw non-phase-conjugate amplified reflection in single
      crystal BaTiO(3) using anisotropic four-wave mixing. We show that the reflected
      beam is polarized orthogonally to the readout beam and that it is a true
      reflection of the image beam, not a phase conjugate. The maximum reflectivity
      measured was approximately 200%.

PMID- 19746030
TI  - Solitary thermal shock waves and optical damage in optical fibers: the fiber
      fuse.
AB  - Fresh experimental and theoretical results on thermally induced catastrophic
      breakdown (the fiber fuse) in optical fibers are presented, including the
      observation that the damage is not always irreversible and an analysis of the
      complex unsteady absorption-heat-conduction process that controls the effect.
      Good agreement with experiment is obtained with just two independent parameters.
      The analysis shows that the fiber fuse is a new kind of solitary thermal shock
      wave in whose leading edge the temperature gradients can reach several thousand
      kelvins per micrometer.

PMID- 19746032
TI  - Second-harmonic generation in single-mode and multimode fibers.
AB  - We report efficient second-harmonic generation in several commercially available
      telecommunication-grade single-mode and multimode optical fibers. We have
      investigated the effect of standard dopants such as germanium, phosphorous, and
      fluorine, and find that the efficient second-harmonic generation is associated
      with germaniarelated photosensitive color centers. We observed a 1.5% conversion
      efficiency in single-mode fibers with germanium-, phosphorous-, and fluorine
      doped cores and high hydroxyl levels.

PMID- 19746031
TI  - Solitons in the region of the minimum group-velocity dispersion of single-mode
      optical fibers.
AB  - Pulses launched with their central wavelength in the region of the minimum
      dispersion wavelength of a single-mode optical fiber exhibit a distinct spectral
      splitting due to the nonlinearity. As a solitary wave evolves, the corresponding
      central wavelength of this component frequency downshifts while the dispersive
      wave is upshifted, in qualitative agreement with theoretical prediction.

PMID- 19746033
TI  - Optical Kerr switch using elliptical-core two-mode fiber.
AB  - A new optical-optical switching technique is proposed and demonstrated with a
      probe-pump scheme, utilizing nonlinear differential phase shift between two
      spatial modes in a highly elliptical-core fiber. The probe beam is switched from
      one intensity-lobe position of the fiber output radiation pattern to the other in
      a 33-m-long fiber at a pump power of 1.6 W.

PMID- 19746034
TI  - Nonincremental coherent optical fiber sensor.
AB  - A novel coherent optical fiber sensor for nonincremental measurements of phase
      conveyed information is reported. When the frequency of a laser source is
      sinusoidally modulated, a nonincremental measurement can be processed with the
      same frequency-demodulation treatment as used for an incremental one. This method
      is applied to a polarimetric fiber-optic sensor to obtain the absolute
      temperature measurement in the range of 20-100 degrees C. A rotating half-wave
      plate gives the polarimetric setup the frequency carrier essential for the
      demodulation process. Experimental data confirming the theoretical predictions
      are reported together with the measured sensitivity values.

PMID- 19746035
TI  - Fiber-optic temperature sensing with ultrathin silicon etalons.
AB  - We report fiber-optic temperature sensing with an optically thin silicon etalon.
      A simple fabrication technique by direct deposition of silicon onto the fiber
      tip, a wide range of operating wavelengths from 1500 nm down to 800 nm, and the
      applicability for temperature sensing well above 400 degrees C are the most
      prominent features of the silicon etalon sensor.

PMID- 19746036
TI  - Fiber-optic heterodyne gyroscope using two optical beams with orthogonally
      polarized components.
AB  - A novel scheme for a fiber-optic heterodyne gyroscope is proposed. This scheme
      produces two beat-photocurrent signals, including the Sagnac phase shift of
      opposite sign. The phase-difference measurement of these signals enables us to
      cancel their common phase factor but to obtain twice the Sagnac phase shift. The
      operation principle is verified experimentally.

PMID- 19746037
TI  - Planar flexible fiber-optic interferometric acoustic sensor.
AB  - A planar flexible fiber-optic interferometric acoustic sensor has been developed
      by wrapping optimized single-mode fibers in a planar spiral form and then
      embedding the fiber in a thin polyurethane layer. Both the acoustic and the
      acceleration responses have been found to compare favorably with those of a
      planar polyvinylidene fluoride sensor of similar geometry.

PMID- 19746038
TI  - Pure phase bistability with a nonlinear slab waveguide.
AB  - We describe the bistable behavior of a nonlinear triple-boundary slab waveguide.
      We show that, in addition to the previously reported reflected intensity
      bistability, this device exhibits bistability in the phase of the reflected beam.
      It is shown that pure phase signal bistability is possible. A system based on the
      Mach-Zehnder interferometric configuration is proposed to achieve a high-contrast
      bistable switch.

PMID- 19746039
TI  - Discrete self-focusing in nonlinear arrays of coupled waveguides.
AB  - We show that a nonlinear array of coupled waveguides can exhibit discrete self
      focusing that in the continuum approximation obeys the so-called nonlinear
      Schrodinger equation. This process has much in common with the biophysical model
      of Davydov.

PMID- 19746040
TI  - High-quality LiTaO(3) integrated-optical waveguides and devices fabricated by the
      annealed-proton-exchange technique.
AB  - High-quality single-mode LiTaO(3) integrated-optical waveguides and devices were
      fabricated below the Curie temperature by the annealed-proton-exchange technique.
      The waveguides had a high polarization extinction (51 dB), low propagation loss
      (<0.25 dB/cm), and low fiber-to-waveguide coupling loss (0.5 dB per junction) at
      0.82 microm. The device-measured r(33) (29.9 x 10(-12) m/V) electro-optic
      coefficient indicates no change in its value from that of bulk LiTaO(3).

PMID- 19746041
TI  - Stable intracavity doubling of orthogonal linearly polarized modes in diode
      pumped Nd:YAG lasers.
AB  - The stability of the output light from a diode-pumped intracavity frequency
      doubled Nd:YAG laser was studied. An intracavity nonlinear crystal, such as Type
      II phase-matched potassium titanyl phosphate, was used for frequency doubling.
      The incident beam consisted of two orthogonal linearly polarized modes. When the
      polarization eigenvectors were parallel to the E and O axes of the crystal, a
      large amplitude fluctuation was observed; however, when the azimuthal angle
      between the polarization eigenvectors and the axis was 45 degrees , the light
      output was stabilized. The experimental results are explained by analyzing the
      coupling of the two orthogonal linearly polarized modes through a sum-frequency
      generation process.

PMID- 19746042
TI  - Alexandrite laser frequency doubling in beta-BaB(2)O(4) crystals.
AB  - Efficient and tunable coherent ultraviolet (360-390 nm) generation in beta
      BaB(2)O(4) crystals using type-I phase matching at room temperature is presented.
      The phase-matching angle is characterized with an alexandrite laser with a
      wavelength tuning range of 725-785 nm. The crystal angular bandwidth of 0.9 mrad
      cm and spectralbandwidth of 1.15 nm-cm are also measured. UV output pulse energy
      of 105 mJ at 378 nm with 31% energy conversion efficiency is achieved.

PMID- 19746043
TI  - Passive mode locking of a cw energy-transfer dye laser operating in the infrared
      near 800 nm.
AB  - The cw tuning range, and subsequent passive mode locking of a new argon-ion
      pumped energy-transfer dye laser operating in the near IR, is reported for the
      first time to our knowledge. The gain medium, consisting of an energytransfer
      mixture of Pyridin 1 as the donor dye and Rhodamine 800 as the acceptor dye, has
      been found to lase continuous waves from 742 to 823 nm. Passively mode locked
      with bis-4-(1-ethylquinoline) [gamma-4'-(1'-ethylquino-line)] pentamethine
      cyanine diiodide dye, this active medium yielded sub-500-fsec pulses from 783 to
      815 nm in a linear cavity, with pulses as short as 260 fsec being generated.

PMID- 19746044
TI  - Two-photon absorption at 248 nm in ultraviolet window materials.
AB  - Two-photon-absorption coefficients are measured for fused silica, LiF, and the
      alkali earth halides BaF(2), SrF(2), CaF(2), and MgF(2), using 0.7-psec, 248-nm
      pulses with intensities in the range (0.5-30) x 10(10) W/cm (2) . The conse
      quences of these measurements in the design of high-brightness excimer lasers are
      discussed.

PMID- 19746045
TI  - Matched filtering for efficient cleanup of strongly distorted beams.
AB  - Efficient one-way cleanup of laser beams can be accomplished by holographic
      matched filtering. Severe amplitude and phase distortions, such as those caused
      by passage through multimode fibers or ground-glass diffusers, can be compensated
      for, with theoretical efficiencies of the order of 50% for light in a single
      state of polarization. Experiments have confirmed the improvement in beam
      quality.

PMID- 19746046
TI  - GaAlAs laser diode frequency locked at the D(2) line of Cs atoms in an atomic
      beam.
AB  - A GaAlAs laser diode has been locked to the D(2)transition of Cs atoms in an
      atomic beam. Measured frequency stabilities are 1 x 10(-10) (0.1 sec), 8.4 x 10(
      12) (1 sec), 2.2 x 10(-12) (10 sec), and 7.8 x 10(-13) (100 sec). This system has
      been successfully applied to an optically pumped Cs-beam frequency standard.

PMID- 19746047
TI  - Design and performance of a few-kilohertz-linewidth dye laserstabilized by
      reflection in an optical resonator.
AB  - Ultrahigh-resolution spectroscopy is limited by the spectral quality of lasers.
      We describe a servo system that stabilizes a dye laser by reflection in an
      optical resonator, which provides an error signal. We analyze the error signal to
      determine the spectral performance of the dye laser, which is shown to have a
      Gaussian-shaped spectrum with a width of less than 4 kHz.

PMID- 19746048
TI  - Interference-filter-tuned, alignment-stabilized, semiconductor external-cavity
      laser.
AB  - We compared the angular alignment tolerance and the tuning range of a novel
      interference-filter-tuned semiconductor external-cavity laser based on a
      degenerate resonator with characteristics similar to those of a conventional
      grating-tuned external-cavity laser using a 1300-nm In GaAsP Fabry-Perot laser
      with an antireflection-coated facet as the gain medium. The interference-filter
      cavity had a 260-fold greater alignment tolerance (+/-26 versus +/-0.1 mrad) and
      nearly the same tuning range (90 versus 110 nm) as the grating-tuned cavity.

PMID- 19746049
TI  - Induced amplitude-modulation instability in single-mode optical fibers.
AB  - Induced modulation instability in a lossless optical fiber is studied by means of
      numerical simulation. Compression ratios and optimum fiber lengths required to
      achieve a train of short pulses at the output of the fiber are presented in
      normalized form.

PMID- 19746050
TI  - Theoretical analysis of metal-clad single-mode fiber-type polarizers.
AB  - We present a method, based on the equivalent-current theory of optical waveguide
      coupling, by which metal-clad optical fiber polarizers can be analyzed. Good
      agreement between theoretical predictions and previously published experimental
      results is attained.

PMID- 19746051
TI  - Dopant diffusion loss mechanism in high-birefringent-fiber fused couplers.
AB  - The observation of dopant diffusion during the tapering of high-birefringent
      fibers that increases with initial modal birefringence is reported. The resulting
      reduction in the core-cladding index difference is postulated to result in an
      increased taper transmission loss and is shown to correspond to increased 3-dB
      fused-coupler insertion loss.

PMID- 19746052
TI  - Single-mode electric-field-sensitive fiber jacketed with vinylidene fluoride
      trifluoroethylene copolymer.
AB  - An integrated phase modulator is made by coating single-mode fibers with a
      radially poled vinylidene fluoride-trifluoroethylene copolymer. The performance
      of the fiber as an optical phase modulator was demonstrated over a wide frequency
      range of 20-50 MHz. A phase sensitivity of 2.1 x 10(-5) rad/(V/m) per meter of
      fiber is measured in the low-frequency region and 3.5 x 10(-6) rad/(V/m) per
      meter of fiber is measured in the high-frequency region. At frequencies higher
      than 1 MH(z), the optical response is dominated by radial resonances of the fiber
      jacket composite.

PMID- 19746053
TI  - Stretch-dependent extinction ratio in a birefringent single-mode optical fiber.
AB  - The stretch-dependent extinction ratio for a birefringent single-mode fiber is
      examined. This ratio exhibits a quasi-periodic change as the fiber is axially
      stretched. This effect can be explained as the power transfer from alinearly
      polarized guided HE(11) mode to an orthogonally polarized HE(11) that is due to
      mode coupling.

PMID- 19746054
TI  - Design principle for a circularly birefringent optical fiber.
AB  - A suitable cross section incorporating material anisotropy is shown to give
      circular birefringence in a slowly spun monomode fiber. It is assumed that the
      fractional variation Deltan/n of the refractive index satisfies the weak guidance
      condition Deltan/n << 1 and that the period (or pitch) p of the spun fiber is
      large enough so that the fundamental modes remain effectively bound. Under these
      assumptions the magnitude of the circular birefringence can be calculated from
      solutions of the scalar wave equation and in any case lies between the limits (0,
      4pi/p). The value is zero in the absence of material anisotropy. The required
      material anisotropy could be produced by stress implanted in the core.

PMID- 19746055
TI  - Observation of input-polarization-induced phase noise in interferometric fiber
      optic sensors.
AB  - It is shown that polarization fluctuations in the input fiber to an
      interferometric sensor can result in the generation of excess phase noise in the
      output. Experimental observations of this phenomenon are compared with
      theoretical models, and the impact of this noise source in interferometric
      sensors is briefly discussed.

PMID- 19746056
TI  - Dual-sensor technique for extending the dynamic range of a fiber-optic
      interferometric sensor.
AB  - A sensor consisting of two fiber-optic interferometers of slightly different
      sensitivities can offer both high sensitivity and a wide dynamic range when the
      phase difference between the two interferometer outputs is used to identify the
      order of the fringe from either interferometer output. This technique is
      demonstrated with a polarimetric temperature sensor utilizing two different
      lengths of stress-induced birefringent fibers as sensing elements.

PMID- 19746057
TI  - Photochromic gratings in photorefractive materials.
AB  - The steady-state and dynamic behavior of absorption and phase gratings in semi
      insulating GaAs and InP have been studied by four-wave mixing. These measurements
      permit independent study of the space-charge-field screening kinetics and free
      carrier recombination kinetics in these materials. The study is important both
      for the design of optimized materials for photorefractive applications and for
      the characterization of the defect electronc structure in these materials.

PMID- 19746058
TI  - Time-integrating interferometry using photorefractive fanout.
AB  - We have experimentally demonstrated a single-beam interferometer that effectively
      subtracts an exponentially weighted history of the input from the current value,
      thus functioning as a novelty filter. The single-beam interferometer uses signal
      depletion due to noise amplification (fanout) in a specially cut crystal of
      photorefractive BaTiO(3). To demonstrate its real-time operation we used a Hughes
      liquid-crystal light valve to convert a video image into a phase- and/or
      amplitude-modulated input signal. Potential applications of this interferometer
      include image-clutter removal, motion detection and tracking, edge enhancement,
      and image time differentiation.

PMID- 19746059
TI  - Optical nonlinearities in Al(x)Ga(1-x)As/GaAs asymmetric coupled quantum wells.
AB  - Optical nonlinearities of Al(x)Ga(1-x)As/GaAs asymmetric coupled quantum wells
      within a p-i-n structure have been observed by using time-resolved spectroscopy.
      Under photoexcitation, exciton absorption lines exhibit spectral shifts of as
      much as approximately 1 meV. The recovery times of these spectral shifts are of
      the order of hundreds of picoseconds when the excitation photon is above the
      lowest exciton state but become less than 10 psec when excitation is below the
      lowest exciton state, indicating a virtual process. The behavior of these
      spectral shifts is consistent with the presence of a polarization induced by
      optical pumping. The polarization is believed to be due to the excitons that have
      nonvanishing electric dipole moments along the axis of the asymmetric coupled
      quantum wells.

PMID- 19746060
TI  - Supercontinuum generated by six-photon mixing.
AB  - We obtain the shape, phase, and spectral distribution of an ultrafast pulse
      propagating in a chi((5)) medium (six-photon mixing). The calculation is
      performed in the plane-wave approximation for a dispersionless medium but with
      self-steepening present.

PMID- 19746061
TI  - Rise-fall ambiguities and their removal from frequency-domain nonlinear-optical
      techniques.
AB  - Most frequency-domain nonlinear-optical techniques measure only the magnitude of
      the Fourier transform of a temporal response and, hence, do not uniquely
      determine the response. We show that, for the commonly used response, h(t) = A
      exp(-t/tau(f)) + B exp(-t/tau(s)),where A identical with alpha/tau(f) and B
      identical with (1 - alpha)/tau(s), the spectral line shape can always be fitted
      by two different values of alpha. A measurement of the optical Kerr transient of
      carbon disulfide illustrates this ambiguitv. We also demonstrate a single-scan
      method that is free from such ambiguities. It involves adding coherent background
      with a nonzero quadrature-phase wavelength.

PMID- 19746062
TI  - Orientational dependence of degenerate four-wave mixing in multiple-quantum-well
      structures.
AB  - The transient grating technique is used to demonstrate how the temporal response
      of four-wave mixing in multiple-quantum-well structures depends on sample
      orientation. Variation of the decay times associated with the short-period
      grating in a phase-conjugate geometry between 40 and 500 psec is demonstrated in
      a GaAs/AlGaAs multiple-quantum-well structure and interpreted in terms of the
      large anisotropy in the carrier diffusion.

PMID- 19746063
TI  - Optical solitary waves induced by cross-phase modulation.
AB  - We show that an optical pulse can propagate undistorted as a bright solitary wave
      in the normal dispersion regime when it couples through cross-phase modulation to
      a dark pulse in the anomalous dispersion regime.

PMID- 19746064
TI  - Cross-talk effects in multiplexed volume holograms.
AB  - Various fundamental cross-talk effects that limit the information storage
      capacity of the spatial-frequency-multiplexed Fourier-transform volume holograms
      are identified and analyzed. The methods for eliminating the identified cross
      talk effects are presented. The signal-to-noise ratio, which determines the
      actual storage capacity, is derived.

PMID- 19746065
TI  - Photorefractive holographic recording in strontium barium niobate fibers.
AB  - We describe what are to our knowledge the first photorefractive holographic
      recordings in a fiber. A plane-wave reference and an image-carrying object beam
      are incident upon the fiber in a reflection geometry. We report results on the
      angular sensitivity of the recordings, the image quality, and readout efficiency
      as a function of the reference-wave input angle when the object wave propagates
      along the bore of the fiber. These experiments are carried out for two relatively
      short, 4- and 8-mm, multimode 1-mm-diameter fibers. The results suggest that an
      array of fibers might favorably replace bulk materials for certain computer and
      signal-processing applications.

PMID- 19746066
TI  - Enhanced nondestructive holographic readout in strontium barium niobate.
AB  - We describe a novel procedure for obtaining enhanced nondestructive holographic
      readout in SBN, where the key new ingredient is utilization of degrees of freedom
      in polarization of the reconstruction beam. The effect also involves spatial
      frequency and the applied voltage during both the recording and the
      reconstruction. The reconstructed beam first drops in intensity but subsequently
      grows in strength above the starting value, approaching 100% efficiency in some
      cases. More than 6 h of continuous readout has been achieved, with efficiency
      remaining strong enough to give more than 10(9) 10-microsec readouts with signal
      to-noise ratios exceeding 20 dB.

PMID- 19746067
TI  - Combining low aberrations and high diffraction efficiency in holographic optical
      elements.
AB  - A method for designing and recording holographic optical elements that have low
      aberrations and high efficiencies is presented. It is based on incorporating a
      holographic element with low aberration into a final element in order also to
      achieve high diffraction efficiency.

PMID- 19746068
TI  - Self-pulsing of the laser light transmitted by a nonlinear liquid-crystal
      interface near the phase transition.
AB  - We report bistability and self-pulsing effects in the switching from total
      internal reflection to a transmitting state at a glass-liquid-crystal interface.
      The role of the phase transition to the isotropic state is underlined, and the
      generation of 20-msec pulses from a continuous laser beam is observed.

PMID- 19746069
TI  - Optical thresholding and switching using a fiber-coupled phase-conjugate mirror.
AB  - A fiber-coupled-ring passive phase-conjugate mirror is used to achieve mutual
      thresholding free of bistability effects and to obtain switching among several
      mutually incoherent light beams.

PMID- 19746070
TI  - Model for an incoherent optical neuron that subtracts.
AB  - An incoherent optical neuron is proposed that subtracts inhibitory inputs from
      excitatory inputs optically by utilizing two separate device responses.
      Functionally it accommodates positive and negative weights, excitatory and
      inhibitory inputs, and nonnegative neuron outputs, and it can be used in a
      variety of neural network models. An extension is given to include bipolar neuron
      outputs in the case of fully connected networks.

PMID- 19746071
TI  - Free-space folded-path optical programmable logic array.
AB  - A new method to realize a medium-scale, free-space optical programmable logic
      array is proposed. By using either a two-dimensional optical spatial light
      modulator or an array of one-dimensional spatial light modulators inside a lens
      based multiple-beam-path cavity, an array of optical multiple-variable logic
      product terms is generated. This device, together with a programmable multiple
      variable OR matrix, can be used to implement any Boolean combinatorial logic
      operations. For an optical binary combinatorial logic computation, the proposed
      method efficiently uses three-dimensional space and optical elements. Preliminary
      experimental results obtained using an inexpensive liquid-crystal television are
      included.

PMID- 19746072
TI  - Incorporation of imaging into a temporal coherence sensor.
AB  - An image-processing technique based on temporal coherence differences in a scene
      is described. Resultant processed images are presented that demonstrate an
      increase in the signal-to-clutter ratio of the order of 10(2) for a He-Ne laser
      in a white-light background (FWHM 200 nm). Problems of processing speed, dynamic
      range, and image misalignment are addressed. Modifications in both the optical
      design and electronic signal processing are proposed. Comparison with nonimaging
      experiments indicates that signal-to-clutter gains approaching 10(8) are
      feasible.

PMID- 19746073
TI  - Subpicosecond-pulse generation through cross-phase-modulation-induced
      modulational instability in optical fibers.
AB  - We report subpicosecond-pulse generation at 1.319 microm in a single-mode optical
      fiber by modulational instability induced through cross-phase modulation by 1.06
      microm pulses propagating in the normal dispersion regime. Pulse-repetition rates
      approaching 300 GHz were achieved.

PMID- 19746074
TI  - Femotosecond switching in a dual-core-fiber nonlinear coupler.
AB  - We report all-optical switching of 100-fsec pulses in a fused-quartz dual-core
      fiber directional coupler. The length of the device is 0.5 cm, and the switching
      power is 32 kW. Pulses are routed to either of two separate fiber guides,
      depending on the input power. Measurements of pulse reshaping by the nonlinear
      coupler provide compelling evidence of the device's ability to response on a
      femotosecond time scale.

PMID- 19746075
TI  - Binary-intensity ratios by the fork algorithm.
AB  - The fork algorithm for accurately estimating the intensity ratio of binary stars
      from speckle interferometry data is presented. For brighter stars simulation
      results suggest that the fork algorithm can attain a signal-to-noise ratio
      roughly 10 times greater than that of other algorithms, such as triple
      correlation and shift-and-add. The results of the application of the algorithm to
      Capella (Alpha Aurigae) data are described.

PMID- 19746076
TI  - High-sensitivity detection of NO in a flame using a tunable ArF laser.
AB  - A tunable, narrow-band ArF laser has been used for laser-induced fluorescence
      detection of NO in natural abundance in a flame experiment. P and R branches of
      the D(2)Sigmaupsilon' = 0?X(2)Pi(3/2,1/2)upsilon'' transition were observed
      probing rotational states between J'' = 19.5 and J'' = 44.5. A single-shot
      detection limit of 1 part in 10(6) was found with a monochromator-based,
      dispersed-fluorescence detection system. In an experimental setup, determination
      of undispersed laser-induced fluorescence detection limits at or below the 1-part
      in-10(9) range should be possible, because the narrow-band laser can be used to
      suppress all other sources of contaminating fluorescence even for detection of
      trace NO. The NO B(2)Piupsilon' = 7 ? X(2)Piupsilon'' = 0 transition was also
      observed in a cell experiment but not in the flame and is reported here.

PMID- 19746077
TI  - Elemental analysis by doubly resonant four-wave mixing in Na-seeded flames.
AB  - Doubly resonant four-wave mixing has been used with two lasers set for resonance
      with the two Na D-line transitions to perform elemental analysis with a Na-seeded
      flame. The method is analogous to phase-conjugation methods where all lasers have
      the same frequency. Strong saturation effects and dynamic Stark splittings are
      observed and used to optimize the mixing efficiency. A nonperturbative theory is
      presented and shown to describe the experimental results.

PMID- 19746078
TI  - Shape distortion of a single water droplet by laser-induced electrostriction.
AB  - Electrostrictive distortions of a flowing water droplet are photographed with a
      framing camera after the laser pulse is shut off. With medium-energy laser
      illumination, large asymmetric bulging from the droplet shadow face precedes
      shape oscillation of the entire droplet. With high-energy laser illumination, the
      bulge acquires a cylindrical shape that can eject a small droplet. The laser
      induced electrostrictive force exerted on a single transparent droplet is
      compared with the surface-tension force.

PMID- 19746079
TI  - Explosive vaporization of single droplets by lasers: comparison of models with
      experiments.
AB  - A computer model of the explosive vaporization of single water droplets by pulsed
      CO(2)-laser radiation is compared with the relevant experiments. The model shows
      excellent quantitative agreement with the experiments, to our knowledge the first
      time such agreement has been observed. The importance of fluid mechanics during
      the pulse is demonstrated, and a second computer model illustrates how a
      spherically symmetric explosion can evolve even under conditions of nonuniform
      heating. The two models reconcile the differences between predictions made by Mie
      theory and observations of droplet heating.

PMID- 19746080
TI  - Polarization, scattering, and coherent effects in semiconductor rib waveguide
      bends.
AB  - The detailed behavior of circular bend attenuation in GaAs/AlGaAs rib waveguides
      is explored both experimentally and theoretically. Our results show a strong
      polarization dependence of the bend loss and coherent coupling oscillations much
      weaker than predicted by beam-propagation calculations.

PMID- 19746081
TI  - Parametric amplification and squeezed-light generation in a nonlinear directional
      coupler.
AB  - A scheme to realize phase-sensitive amplification of light using a nonlinear
      coherent coupler is proposed. Squeezed-light generation with low pump power and
      short interaction length is possible with this technique.

PMID- 19746082
TI  - Reduction intermodulation distortion in interferometric optical modulators.
AB  - A dual-polarization technique for reducing intermodulation distortion in
      integrated-optic interferometric modulators is described. While this technique
      results in a decrease in modulator sensitivity, the intermodulation distortion
      can be significantly reduced for a given depth of optical modulation by adjusting
      the relative amounts of TE and TM optical power. Reductions in intermodulation
      distortion as high as 21 dB were demonstrated by means of this technique with a
      Ti:LiNbO(3) device.

PMID- 19746083
TI  - Effects of tensile stress on the R lines of Cr(3+) in a sapphire fiber.
AB  - We have investigated the spectroscopic properties of a crystalline sapphire fiber
      unintentionally doped with Cr(3+). We find that tensile stress produces blue
      shifts of the R lines and changes in their radiative lifetimes and integrated
      intensities that can be correlated to stress-induced changes of the crystal-field
      parameters.

PMID- 19746084
TI  - Study of the thickness of liquid layers by moire deflectometry.
AB  - We suggest and demonstrate a novel method for studying the thickness of thin
      liquid layers. The method is based on ray-deflection analysis of a beam reflected
      from the edge of the layer and on studying the topography of the layer.

PMID- 19746085
TI  - Fission of optical solitons induced by stimulated Raman effect: errata.

PMID- 19746086
TI  - Role of intensity fluctuations in laser-beam apodization with a graded random
      phase window.
AB  - Analysis indicates that a transparent window with graded random surface
      modulation will apodize a laser beam. Following the apodizer the laser beam
      consists of a scattered component of mean intensity I(s) and an apodized
      component of mean intensity I(a). The apodizer intensity transmission is exp[
      k(2)(n-1)(2)t( 2)(r)], where t( 2)(r)is the window surface modulation mean
      squared amplitude, k is the radiation wave number, and n is the window refractive
      index. Interference between the scattered and unscattered radiation produces
      intensity fluctuations similar to laser speckle. For high-power applications,
      minimization of the probability of optical damage due to intensity fluctuations
      requires that I(a)/I(s) greater, similar 10(2).

PMID- 19746087
TI  - Measurements of scattering of light from layered microspheres.
AB  - Experimental elastic-scattering characteristics of layered microspheres are
      reported. Single particles consisting of glass cores coated with glycerine are
      suspended in an evacuated quadrupole trap, and scattered light intensity is
      measured at a fixed angle as the glycerine evaporates. The results are compared
      with those calculated for concentric spheres using the Mie theory. Excellent
      agreement is obtained for glycerine layers of thickness less than 700 nm. For
      thicker layers, differences occur that are attributed to the effect of gravity on
      particle structure.

PMID- 19746088
TI  - Resistance of holograms made in Polaroid DMP128 photopolymer to ionizing
      radiation damage.
AB  - Because of their light weight and general wave-front-transforming ability,
      holograms appear potentially useful as beam correctors and collimators for diode
      laser arrays in intersatellite optical data links. However, to survive in space a
      hologram must withstand damage from electrons and protons trapped in the Van
      Allen belts. We have found that holograms made with Polaroid DMP128 photopolymer
      on Suprasil-2 can withstand 63-MeV protons up to a total dose of 2 Mrad (Si) and
      withstand (60)Co gamma rays up to a total dose of 2 Mrad (Si) without loss of
      diffraction efficiency. It appears that these holograms are sufficiently
      radiation hard for space application.

PMID- 19746089
TI  - Phase-only computer-generated hologram produced by an ion-exchange technique.
AB  - We have produced a highly efficient phase-only hologram, in which the refractive
      index of the substrate is modified by using an ion-exchange method. This binary
      phase-only hologram is produced using a conventional binary hologram as a mask
      for the ion exchange. A simplified theory of the phase-only hologram is presented
      along with a description of the fabrication method and the experimental test
      results.

PMID- 19746090
TI  - Deep-red holography using a junction laser and silver-halide holographic
      emulsion.
AB  - We have investigated exposure parameters for deep-red holography using a junction
      laser and silver-halide holographic emulsion to record single-beam reflection
      phase-volume holograms recorded and reconstructed at a wavelength of 750 nm. We
      present measurements of the variation of diffraction efficiency and its
      derivative efficiency with exposure energy. These measurements are compared with
      the corresponding values obtained when using a He-Ne laser for recording; similar
      diffraction efficiencies have been obtained with both kinds of laser.

PMID- 19746091
TI  - Channeling of atoms in a standing spherical light wave.
AB  - One-dimensional localization of sodium atoms in a standing spherical light wave
      has been observed. The atoms have an oscillatory motion with an amplitude of
      approximately lambda/10 along the nodes (or loops) of the wave.

PMID- 19746092
TI  - Subpicosecond time-resolved vibrational spectroscopy by transient infrared
      absorption.
AB  - A technique to record transient vibrational spectra with 0.5-psec resolution is
      reported. The apparatus is based on seeded optical parametric amplification. A
      study of the microscopic details of the photodissociation of carboxyhemoglobin is
      described as an example.

PMID- 19746093
TI  - Laser properties of selectively excited YAlO(3):Er.
AB  - We report on the influence of selective excitation on the laser emission of
      YAlO(3):Er at 2.73, 2.79, and 2.92 microm. Selective excitation is done by
      filtering the pump light of a Xe flash lamp. This leads to a reduction of the
      thermal load on the crystal and laser threshold, allowing repetition rates up to
      125 Hz.

PMID- 19746094
TI  - Cascaded, stagger-tuned, broadband, low-ripple optical amplifiers.
AB  - We show theoretically that the gain spectrum obtained by cascading two or more
      semiconductor optical amplifiers can have a ripple amplitude that is
      significantly smaller than that currently attainable with a single stage of
      optical amplification. For example, by cascading two stagger-tuned amplifiers,
      each having 10 dB of coupling loss and facet reflectivities of 10(-3), one can
      achieve a net (fiber-to-fiber) gain of 30 dB with less than 2 dB of ripple
      amplitude. We also show that, under some conditions, simple cascading of optical
      amplifiers, without the stagger tuning and associated control, can lead to low
      ripple, high-gain optical amplification.

PMID- 19746095
TI  - Fast frequency tuning and phase locking of diode-pumped Nd:YAG ring lasers.
AB  - We have built a diode-pumped single-mode monolithic Nd:YAG ring-laser oscillator
      that can be tuned piezoelectrically over several tens of megahertz in a few
      microseconds. Frequency stability over 1 msec is better than 500 Hz. We have
      electronically phase locked two lasers for periods of minutes with phase noise of
      29 mrad rms.

PMID- 19746096
TI  - Continuous-wave dye laser pumped by a high-pressure argon arc.
AB  - Continuous-wave operation of a Rhodamine 6G dye laser, incoherently pumped by a
      high-pressure argon arc, has been achieved. A special electrode design reduces
      melting of the electrode tips, and thus the arc provides the necessary brightness
      for periods of the order of hours.

PMID- 19746097
TI  - Room-temperature operation of a Co:MgF(2) laser.
AB  - A normal-mode, pulsed Co:MgF(2) laser has been operated at room temperature for
      the first time to our knowledge. Continuous tuning from 1750 to 2500 nm with
      pulse energies up to 70 mJ and 46% slope efficiency was obtained with a 1338-nm
      Nd:YAG pump laser.

PMID- 19746098
TI  - Stable, pulsed, color-center laser in pure KCl tunable from 1.23 to 1.35 microm.
AB  - Stable, tunable, pulsed laser operation based on the N(2) color center in
      additively colored pure KCI is reported. The laser tunes smoothly from 1.23 to
      1.35 microm when pumped by a 1.06-microm Q-switched Nd:YAG laser at kilohertz
      repetition rates. 42-mW average output power at 1.28 microm was achieved for 1-W
      average incident pump power. No power fading has been observed over several weeks
      of day-to-day operation.

PMID- 19746099
TI  - Laser-linewidth measurement with a Fizeau wavemeter.
AB  - It is shown theoretically and experimentally that a Fizeau wedge wavemeter
      typically used to measure laser wavelength can also be used to measure the
      linewidth of a pulsed or cw laser. Linewidths as small as a few hundred megahertz
      can be measured by choosing the thickness of the wedge properly.

PMID- 19746100
TI  - Tight focusing and blue shifting of millijoule femtosecond pulses from a conical
      axicon amplifier.
AB  - We focus millijoule femtosecond pulses to a spot radius of 2 microm after
      amplification free of phase-front distortion in a Nd:YAG-pumped conical axicon
      dye cell. Peak focal intensities reach 10(16) W/cm(2) , creating an intense spark
      that is caused by air breakdown at the focus. Intensity-dependent blue shifts of
      the pulse spectrum as large as 11 nm are observed as a result of temporally
      asymmetric self-phase modulation in the air-breakdown plasma.

PMID- 19746101
TI  - Quasi-linear ring colliding-pulse mode-locked femtosecond laser using binary
      energy-transfer gain dye mixture.
AB  - A new method for femtosecond pulse generation using a binary energy-transfer dye
      mixture for the gain medium in a novel linear ring colliding-pulse mode-locked
      dye-laser configuration is reported. Pulses of 30-fsec duration and 18.7-nm
      spectral width are routinely generated.

PMID- 19746102
TI  - Characterization of a high-gain picosecond flash-lamp-pumped Nd:YAG regenerative
      amplifier.
AB  - We evaluate the performance of a novel 10-Hz picosecond Nd:YAG regenerative
      amplifier configured as a selffiltering unstable resonator. Pulse energies of ~60
      mJ in ~100 psec at 1.06 microm are achieved using a single 6-mm-diameter Nd:YAG
      rod, while mode-matching requirements are minimized.

PMID- 19746103
TI  - Holographic interferometry of ultrafast transients by photochemical hole burning.
AB  - A novel approach for interferometric analysis of ultrafast transient processes as
      short as 10(-13)-10(-14) sec is suggested. The method of holographic storage of
      ultrafast time-space images in spectrally selective hole-burning materials is
      used. It is shown that differential interferometric comparison of time-space
      images, which are permanently stored, provides an effective means to resolve
      ultrafast transient signals in space and in the spectral domain.

PMID- 19746104
TI  - Single-shot measurement of subpicosecond KrF pulse width by three-photon
      fluorescence of the XeF visible transition.
AB  - The intensity of the XeF C-A transition induced by a subpicosecond KrF laser is
      shown to have a cubic dependence on KrF laser intensity. The third-order
      autocorrelation technique for measuring the duration of a single KrF
      subpicosecond pulse has been developed utilizing this visible transition. A pulse
      width of 220 fsec was successfully measured with a high contrast of ~10. The
      visible fluorescence is more useful to researchers than vacuum-UV fluorescences.
      Furthermore, this simple technique may be applied over a wide UV wavelength
      region from 204 to 306 nm.

PMID- 19746105
TI  - Prepulses as a distinctive characteristic of resonant pulse propagation in
      degenerate atomic media.
AB  - Prepulses are associated with resonant pulse propagation in degenerate media. We
      show numerically that the appealing explanation of prepulses in terms of separate
      pulse propagation dynamics for strong and weak dipole channels in a Q(2)
      degenerate atomic medium is incorrect, although prepulses remain a characteristic
      of degenerate media.

PMID- 19746106
TI  - Reflection and transmission of self-focused channels at nonlinear dielectric
      interfaces.
AB  - We show with an extensive numerical study that the global reflection and
      transmission properties of a finite-width optical self-focused channel incident
      at an oblique angle to an interface separating two self-focusing nonlinear media
      can be categorized into three distinct regimes of behavior as the incidence angle
      is varied through the angle for total internal reflection. The largest regime in
      parameter space is the nonlinear regime, where a channel undergoes either total
      internal reflection or transmission, in marked contrast to the well-known linear
      Snell's law behavior. The beam asymptotics in this latter region are
      quantitatively explained by a recent equivalent-particle theory.

PMID- 19746107
TI  - Polarization dependence of resonance-enhanced three-photon scattering.
AB  - The polarization properties of stimulated three-photon scattering in a three
      level atomic system are presented. In our investigation of the stimulated
      emission spectrum of Na, we find that interference between the amplitudes of the
      resonant contributions of the Na doublet states results in interesting
      polarization phenomena. Particularly striking is the behavior when the laser is
      tuned near the dispersion-free point. With the laser linearly polarized the
      stimulated three-photon scattering is polarized perpendicular to the laser
      polarization. For circularly polarized excitation, total extinction of three
      photon scattering is observed.

PMID- 19746108
TI  - Optical second-harmonic generation with coupled surface plasmons from a
      multilayer silver-quartz grating.
AB  - We report a theoretical and experimental study of enhanced optical second
      harmonic generation due to excitation of coupled surface plasmons from a thin
      silver grating bounded by two quartz crystals. With incident radiation from a
      Nd:YAG laser, diffracted second-harmonic generation in the n = 1, 0, and -1 modes
      is observed for the coupled surface plasmon fundamental modes. Nonlinear
      reflectance ratios calculated by using the reduced Rayleigh equations are in good
      agreement with the experimental results. Enhancement of the second-harmonic
      generation is limited by the scattering of the long-range surface plasmon mode in
      the thinnest silver films studied.

PMID- 19746109
TI  - Self-bending of a cw laser beam in sodium vapor.
AB  - Continuous-wave self-deflection of an asymmetrical laser beam, with a deflection
      angle up to eight diffraction widths, and strong attenuation of the on-axis
      radiation were achieved in a short sodium-vapor cell. We determined that the
      nonlinear refractive index Deltan varied almost linearly with intensity I, Deltan
      approximately n(2)I, with n(2) ~ -10(-7) cm(2)/W at ~200 degrees C and
      intensities less than 220 W/cm(2).

PMID- 19746110
TI  - Interference-term real-time measurement for self-stabilized two-wave mixing in
      photorefractive crystals.
AB  - We report the real-time direct interference-term measurement for a two-wave
      mixing experiment in photorefractive crystals. Knowledge of the interference term
      may provide information concerning diffraction efficiency, interference pattern
      to-recorded hologram phase shift, and optical activity and anisotropic
      diffraction properties of these materials. This method comprises phase modulation
      of one of the interfering beams and synchronous detection of the first and second
      harmonics in the resulting output irradiance modulation. Simultaneous detection
      of both harmonics enables the measurement to be made even in strongly perturbed
      conditions, since one harmonic is used for measuring and the other is used for
      operating Bi(12)TiO(20) are reported.

PMID- 19746111
TI  - Mirrorless coherent oscillation due to six-beam vectorial mixing in
      photorefractive crystals.
AB  - A cw mirrorless oscillation is observed in a photorefractive LiNbO(3):Cu crystal
      when the crystal is exposed to two nearly counterpropagating pump waves from an
      Ar(+) laser. This oscillation is shown to result from a parametric vectorial six
      beam interaction in a medium with a photovoltaic nonlinearity.

PMID- 19746112
TI  - Multibeam coupling in photorefractive SBN:Ce.
AB  - Theoretical and experimental results are presented for simultaneous multibeam
      coupling in photorefractive SBN:Ce. Within a single crystal, multiple signals are
      amplified through a coupling process that employs a single pump. The coupling
      gain of each signal results from coupling both between the pump and the signal
      and between different signals. The amount of gain that each signal receives is
      dependent on the intensity of the incident signal; thus a competition for the
      gain exists among the various signals.

PMID- 19746113
TI  - Nonlinear transmission and color-center dynamics in germanosilicate fibers at 420
      540 nm.
AB  - We report evidence in support of the view that induced loss and nonlinear
      transmission in pure germanosilicate fibers at blue-green wavelengths are
      governed by the formation (through two-photon absorption), spontaneous and
      stimulated transformation, and bleaching (through single-photon events) of Ge(1),
      Ge(2), and Ge(3) color centers. Using a tunable pulsed-dye laser, the excitation
      spectrum of the induced absorption, its spectral attenuation, and the effects of
      Ge concentration and thermal annealing are investigated.

PMID- 19746114
TI  - Improved mode locking of an F-center laser with a nonlinear nonsoliton external
      cavity.
AB  - We demonstrate that solitons are not essential for the operation of the soliton
      laser. The external cavity employed contains an optical fiber with negative group
      delay dispersion and therefore does not support bright solitons. Thus the
      improved mode locking cannot be attributed to the injection of an N = 2 soliton.

PMID- 19746115
TI  - Raman amplification of modulational instability and solitary-wave formation.
AB  - The effect of synchrohous Raman gain in a single-mode fiber on a weak signal
      exhibiting modulational instability is shown spectrally and temporally to give
      rise to the rapid development of a single ultrashort solitary wave and a lowlevel
      dispersive pedestal.

PMID- 19746116
TI  - Optical fibers with negative group-velocity dispersion in the visible.
AB  - Dispersion measurements have been performed in optical fibers having a
      photoinduced refractive-index grating in the core. The results show that negative
      group-velocity dispersion can be obtained in these fibers over a frequency region
      of 500 MHz for wavelengths shorter than 550 nm.

PMID- 19746117
TI  - Chromatic dispersion limitations due to semiconductor laser chirping in
      conventional and dispersion-shifted single-mode fiber systems.
AB  - The effect of dynamic linewidth broadening due to frequency chirping in directly
      modulated single-mode lasers, combined with dispersive single-mode fibers, has
      been investigated using computer simulation. It has been found that dispersion
      shifted fibers have a potential advantage over conventional single-mode fibers
      for dual-window multigigabit-per-second bidirectional and wavelength-division
      multiplexed transmission systems.

PMID- 19746118
TI  - Performance of a fiber-optic temperature sensor from -200 to 1050 degrees C.
AB  - A reflectively monitored Fabry-Perot temperature sensor is characterized over a
      1250 degrees C temperature range. Dielectric mirrors for the interferometer are
      incorporated into a continuous length of single-mode fiber by a fusionsplicing
      technique. The change in optical phase per unit temperature is nearly constant
      above room temperature but decreases at lower temperatures. Phase-shift data for
      the germania-doped silica fiber used in these experiments are compared with
      calculations based on previously reported information on the temperature
      dependence of refractive index and length in bulk fused silica.

PMID- 19746119
TI  - Self-focusing instability and chaotic behavior of nonlinear optical waves guided
      by dielectric slab structures.
AB  - The propagation of nonlinear optical waves guided by a nonlinear thin film
      bounded by two linear claddings is examined numerically. Numerical results for
      the propagation constant versus the propagation axis indicate that for higher
      order modes the transition from periodic behavior to chaos through period
      doubling is observed as the guided-wave power increases, whereas for the
      fundamental mode an extremely stable self-focusing propagation is possible.

PMID- 19746120
TI  - Generation of a phase-conjugate wave by degenerate four-wave mixing in an
      erythrosin-B-doped planar waveguide.
AB  - A phase-conjugate wave (PCW) generated by degenerate four-wave mixing (DFWM) in a
      nonlinear-optical waveguide excited by a cw Ar-ion laser was observed. The planar
      waveguide consisted of a transparent polyvinyl alcohol layer partly doped with
      erythrosin-B. The DFWM excitation was performed as follows: Two pump waves
      impinged in the interaction region of the waveguide from the outside, and a probe
      wave was introduced into the guiding layer by a prism coupler. A PCW reflectivity
      of 6.3 x 10(-5) outside the prism coupler was obtained at a pump intensity of 1.2
      W/cm(2).

PMID- 19746121
TI  - GaAs/AlGaAs integrated-optic wavelength demultiplexer.
AB  - An integrated-optic dual-channel wavelength (de)multiplexer is demonstrated on a
      GaAs/AlGaAs heterostructure. The device, an asymmetric Mach-Zehnder
      interferometer, operates with a channel separation of 19 nm in the 1500-nm
      wavelength range.

PMID- 19746122
TI  - Stable low-loss proton-exchanged LiNbO(3) waveguide devices with no electro-optic
      degradation.
AB  - Channel waveguides and Mach-Zehnder interferometers were fabricated in LiNbO(3)
      by annealed proton exchange. The waveguides had a loss of 0.15 dB/cm and a fiber
      to-fiber insertion loss of 1.2 dB at 0.8 microm. The measured r(33) electro-optic
      coefficient of the interferometers was 30 x 10(-12) m/V +/-5%, which agrees well
      with theory, indicating that there is no degradation in the r(33) coefficient. No
      variation in insertion loss or switching voltage was observed over 8 months for
      devices stored at room temperature.

PMID- 19746123
TI  - Compact scanning-force microscope using a laser diode.
AB  - We describe a compact scanning-force microscope in which the element that senses
      the amplitude of vibration of a tip interacting with force gradients is the
      cavity of a single-mode laser diode and its integrally built photodiode.

PMID- 19746124
TI  - Spatial coherence discrimination in scattering.
AB  - Expressions are derived, valid within the accuracy of the first Born
      approximation, for the cross-spectral density and for the spectral intensity of
      the field that is produced by scattering of radiation of any state of spatial
      coherence. The results are illustrated by examples that show quantitatively the
      difference between scattering of laser light and of ambient light. It is
      suggested that the dependence of the scattered intensity on the degree of spatial
      coherence of the incident radiation could be utilized to make devices that would
      discriminate between a laser beam and diffuse light.

PMID- 19746125
TI  - Consummate solution to the problem of classical electromagnetic scattering by an
      ensemble of spheres. II: Clusters of arbitrary configuration.
AB  - The order-of-scattering approach developed earlier [Opt. Lett. 13,90 (1988)] and
      applied there to the case of linear chains of spheres is extended to the more
      difficult problem of scattering by clusters of spheres, the centers of which no
      longer need lie on a common axis. To help establish the validity of this most
      general calculation, comparisons are made between theoretical and experimental
      results for triangular and tetrahedral arrays of spheres. We also perform
      calculations based on an older method that requires the inversion of matrices,
      and we find that for the cases considered here the order-of-scattering method is
      substantially faster.

PMID- 19746126
TI  - Polarization dependence of dynamic light scattering by dense disordered media.
AB  - Photon correlation studies of light scattered by a dense disordered medium at and
      around the backscatter direction reveal a polarization dependence of the
      correlation function. This is related to the polarization dependence of the mean
      intensity of the enhanced backscatter associated with coherent cooperative
      effects in such media.

PMID- 19746127
TI  - Analysis of the Lau effect using Walsh functions.
AB  - An experiment similar to the Lau effect but employing the Walsh functions as
      diffracting apertures is performed. The equivalent resonance condition and the
      corresponding intensity light distribution are derived. This approach is used to
      implement a spatial-filtering optical device.

PMID- 19746128
TI  - Refractive-index measurements of the beta'' aluminas.
AB  - The refractive indices of selected monovalent and divalent beta'' alumina single
      crystals are determined using prism refraction techniques. The birefringence is
      found to vary from uniaxial negative to uniaxial positive depending on the
      electronic polarizability of the exchanged ion. Thus, beta'' alumina is a novel
      material in which the magnitude and polarity of the birefringence can be tuned
      simply by ion exchange. The refractive-index data are used to predict an isoindex
      point (n(e) = n(0)) for the mixed-system Na(+)-Ag(+) beta'' alumina compositions.

PMID- 19746129
TI  - Optical Raman heterodyne detection of (27)Al superhyperfine spectra in ruby.
AB  - We report extension of the Raman heterodyne technique for detection of nuclear
      magnetic resonance (NMR) to superhyperfine spectra. NMR of the four nearest
      neighbor sets of (27)A1 (I = 5/2) surrounding Cr(3+) in ruby has been observed
      with high sensitivity using optical excitation of the R(1) line at 693.4 nm.
      Either excited-state or groundstate resonances could be selectively displayed by
      setting the sample temperature to 2 or 7.5 K, respectively. All 40 expected NMR
      resonances were observed, with good agreement obtained between calculated and
      experimental values.

PMID- 19746130
TI  - Very-low-temperature behavior of a micromaser.
AB  - We show that at very low temperatures the steady-state photon statistics of the
      micromaser are stronglv influenced by the existence of trapping states. The
      resulting resonances are a true quantum effect resulting from the granulated
      character of the electromagnetic field.

PMID- 19746131
TI  - Simple model for amplified spontaneous emission in a Ti:A1(2)O(3) amplifier.
AB  - The influence of amplified spontaneous emission on the time-dependent gain of a
      laser amplifier is considered by using a simple model. Experimental measurements
      of Ti:A1(2)O(3) amplifier gain are in excellent agreement with the model.

PMID- 19746132
TI  - Pump excited-state absorption in erbium-doped fibers.
AB  - Ground-state and excited-state absorption spectra covering the wavelength range
      of 450-1050 nm are presented for erbium-doped silica fibers with four different
      core codopants: GeO(2), GeO(2)/B(2)O(3), GeO(2) /P(2)O(5), and Al(2)O(3). It is
      shown that the host glass influences the excited-state absorption spectra and
      that P(2)O(5)- or A1(2)O(3)-codoped fibers are the preferred choice for 514.5-,
      655-, or 807-nm pump wavelengths owing to reduced pump excited-state absorption.
      However, excited-state absorption is still significant at the 807-nm wavelength.
      Pump wavelengths of 524, 532, and 980 nm appear ideal because of the strong
      ground-state absorption and lack of excited-state absorption.

PMID- 19746133
TI  - Composite structures for the enhancement of nonlinear optical materials.
AB  - Calculations of the nonlinear optical behavior are developed for model composites
      consisting of nanospheres with a metallic core and a nonlinear shell suspended in
      a nonlinear medium. The concept for the enhancement of optical phase conjugation
      from all these nonlinear regions is that the optical field can be concentrated
      both inside and in the neighborhood of the metallic core, aided by surface
      mediated plasmon resonance. Calculations for gold cores and aluminum cores
      indicate that phase-conjugate reflectivity enhancements of 10(8) may be possible.

PMID- 19746134
TI  - Self-focusing, self-phase modulation, and diffraction in bulk homogeneous
      material.
AB  - The simultaneous effects of self-focusing, self-phase modulation, and diffraction
      on the propagation of an ultrafast pulse in a homogeneous Kerr medium are
      described. The competing effects of self-focusing and diffraction are shown to
      modify the shape and magnitude of the pulse amplitude and phase. These
      modifications are shown to affect the spectral distribution of the supercontinuum
      from that predicted by the conventional self-phase-modulation theory.

PMID- 19746135
TI  - Coupled cw dye lasers using intracavity four-wave mixing.
AB  - An experimental investigation of laser-oscillator frequency locking by a four
      wave interaction was conducted. An experiment was performed that successfully
      demonstrated the locking of two cw dye lasers using this concept with Na vapor
      serving as the nonlinear (coupling) medium.

PMID- 19746136
TI  - Transverse modulational instabilities for counterpropagating beams in Kerr media.
AB  - Continuous-wave and oscillatory transverse instabilities are predicted for
      counterpropagating waves in Kerr media for both focusing and defocusing
      nonlinearities. Neither a cavity nor a finite response time is required. Computed
      Gaussian-beam results agree well with analytic plane-wave calculations that
      straddle Raman-Nath and Bragg regimes.

PMID- 19746137
TI  - Stimulated Raman scattering in micrometer-sized droplets: measurements of angular
      scattering characteristics.
AB  - Measurements of the angular scattering characteristics of elastic and stimulated
      Raman scattering (SRS) in single (nominal 20-microm-radius) water, ethanol, and
      CC1(4) droplets irradiated with 0.532-microm-wavelength radiation from a pulsed
      laser demonstrate that SRS is more isotropic than elastic scattering yet
      qualitatively mimics angularly smoothed elastic scattering patterns. The angular
      fine structure characteristic of the coherent elastic scattering process is
      lacking in SRS, regardless of whether the SRS derives from multiple orders of
      Stokes shifts, multiple resonances within a single Stokes shift, or single
      resonances within a single Stokes shift.

PMID- 19746138
TI  - Efficient monolithic MgO:LiNbO(3) singly resonant optical parametric oscillator.
AB  - We have operated a monolithic MgO:LiNbO(3) singly resonant optical parametric
      oscillator (OPO) as both a standing-wave and a ring-geometry resonator. The OPO
      was pumped by the second harmonic of an amplified single-mode diode-laser-pumped
      Nd:YAG laser. Pump depletions of greater than 60% were observed when pumping four
      times greater than the 35-W threshold. The OPO output at the resonant signal
      tuned with temperature from 834 to 958 nm, while the corresponding idler tuned
      from 1.47 to 1.2 microm. The spectral characteristics of the OPO signal output
      and the relative merits of a standing wave versus a ring geometry are discussed.

PMID- 19746139
TI  - One-way phase conjugation with partially coherent light and superresolution.
AB  - Limitations on the one-way phase-conjugation technique are described. These
      limitations are reduced or eliminated by reducing the spatial coherence of the
      light and by reducing the aperture of the imaging system. By introducing a
      suitable level of superresolution of the kind previously described as
      superresolution by incoherent-tocoherent conversion, the aperture and coherence
      reductions reduce the effect of the optical path inhomogeneities. However, the
      aperture reduction does not degrade the diffraction-limited resolution limit.

PMID- 19746140
TI  - Angular dependence of phase conjugation in SF(6).
AB  - Optical phase conjugation by degenerate four-wave mixing in SF(6) was studied
      with a cw CO(2) laser. The intensity and angular dependence of reflectivity were
      measured for the 10.6-microm P(18) line. The results verify the predictions of
      the inhomogeneously broadened resonant two-level gas model.

PMID- 19746141
TI  - Erasure rate and coasting in photorefractive barium titanate at high optical
      power.
AB  - The light-induced erasure rate of a photorefractive grating in barium titanate
      scales sublinearly with optical intensity over a range spanning 8 orders of
      magnitude. Additionally, we find that a series of optical pulses is more
      efficient in erasing a photorefractive grating if the repetition rate of the
      pulses is decreased. We postulate that this increase in erasure efficiency is
      caused by a level of shallow traps in the crystal, which permit erasure to
      continue for a few seconds in the dark after the optical pulse has ended, and we
      directly observe this coasting in the dark.

PMID- 19746142
TI  - Solitonlike Stokes pulses in stimulated Raman scattering.
AB  - An analytical solution for compressed solitonlike Stokes pulses created by Raman
      amplification is presented in the limit where the relative velocity between a
      wide pump pulse and the Stokes pulse is large and pump-depletion effects can be
      neglected. The concomitant deviations from the classical soliton shape are shown
      to be harmless for optical communication purposes. In the opposite limit, where
      pump depletion becomes important, cross-phase modulation between the pump and the
      Stokes pulse destroys the conditions for compression during Raman amplification.

PMID- 19746143
TI  - Phase matching the stimulated four-photon mixing process on single-mode fibers
      operating in the 1.55-microm region.
AB  - Phase matching the stimulated four-photon mixing process on single-mode fibers
      reveals information about the dispersion properties of the fiber, in particular,
      the zero-dispersion wavelength. Examples of the expected frequency-shift behavior
      around the zero-dispersion wavelength are given for multiply clad silica glass
      single-mode fibers designed for minimum dispersion operation in the 1.55-microm
      region.

PMID- 19746144
TI  - Polarization coupling in single-mode single-polarization optical fibers.
AB  - Polarization coupling in single-mode, single-polarization optical fibers is
      investigated, and a set of coupled-mode equations for single-mode, single
      polarization fibers including guided and leaky modes is derived.

PMID- 19746145
TI  - Evaluation of length dependence of cutoff wavelength in a cabled fiber.
AB  - The length dependence of the cutoff wavelength of a cabled fiber is examined
      theoretically and experimentally as a function of loop diameter. Evaluation of
      the cutoff wavelength for a cabled fiber is simplified by assuming that loops of
      equal size are inserted on each side of the cabled fiber, and a simple equation
      is derived.

PMID- 19746146
TI  - Practical tuning mechanism for fused-tapered couplers.
AB  - The axial twisting of a fused-tapered single-mode fiber coupler causes optical
      decoupling, which can change the power-splitting ratio of the coupler. Twisting
      of the coupling region causes a redistribution of the modal fields away from the
      coupler axis as a result of an effective refractive-index change. A simple
      analytical expression is derived that describes this decoupling effect. An
      environmentally stable package is implemented that allows a coupler's response to
      be tuned through all possible values.

PMID- 19746147
TI  - Explanation of errors inherent in the effective-index method for analyzing
      rectangular-core waveguides.
AB  - It is shown that use of the effective-index method for a rectangular-core
      waveguide is equivalent to analysis of a pseudorectangular-core waveguide, the
      dielectric constant of which is higher in some of the cladding regions than that
      of the actual waveguide. This explains why the effective-index method gives
      higher values for the propagation constants for the various guided modes than
      other methods and different results depending on whether one starts with the
      longer dimension or the shorter dimension to construct the effective-index
      waveguide.

PMID- 19746148
TI  - All-optical phase- and power-controlled switching in nonlinear waveguide
      junctions.
AB  - We propose and study a novel all-optical waveguide switching element made from a
      nonlinear symmetric junction. Nonlinear index changes break the symmetry of the
      structure and induce routing of the signal to one of two output ports. Power- and
      phase-controlled switching with a weak control signal are possible. The switching
      is insensitive to the precise value of either power or phase and to the structure
      parameters.

PMID- 19746149
TI  - Plane-wave spectrum approach for tilted waveguides.
AB  - Scattering of guided modes from an abruptly terminated waveguide is analyzed
      through an integral-equation formulation. First the boundary-value problem for a
      plane-stratified waveguide with arbitrary profile is reduced to a canonical
      system of surface integral equations. A Born-type iterative procedure is then
      employed to obtain a tractable solution of the scattering field at the
      termination. The specific choice of a tilted planar termination renders an
      explicit closed-form expression for the first Born approximation, represented by
      the plane-wave spectrum of the incident modal field modified by the appropriate
      Fresnel coefficient. Thus previous ad hoc formulations can be recovered as
      limiting cases of the suggested rigorous expansion scheme.

PMID- 19746150
TI  - Losses in semiconductor waveguide S bends fabricated by impurity-induced layer
      disordering.
AB  - An experimental comparison is made between the losses of S bends fabricated by
      impurity-induced layer disordering in GaAs-AlAs superlattices. For parallel
      waveguides offset by 100 microm, transition lengths corresponding to 3-dB excess
      loss were found to be approximately 290 microm for approximately single-mode S
      bends in the form of a raised cosine and approximately 335 microm for bends in
      the form of two constant-radius-of-curvature sections. These buried-channel bends
      appear to have losses that compare favorably with those formed from rib
      waveguides.

PMID- 19746151
TI  - Formation of negative-index-change waveguide lenses in LiNbO(3) by using ion
      milling.
AB  - We report, for the first time to our knowledge, fabrication of two types of
      negative-index-change waveguide lens in LiNbO(3) by using ion milling. The first
      type is an analog Fresnel lens formed by grooves milled into the waveguide. The
      second is a hybrid lens that combines analog Fresnel zones in the central region
      with chirp gratings on the sides formed by the same means. We have obtained
      simultaneously high-efficiency and near-diffraction-limited focusing
      characteristics in both types of lens. The ion-milling technique employed should
      be capable of producing similar lenses in any other waveguide substrate, such as
      GaAs.

PMID- 19746152
TI  - Optical implementation of binary symmetric logic functions.
AB  - Optical implementations of binary multiple-variable symmetric logic functions are
      proposed. By using a triangular array of lossless beam splitters together with
      optical on-off switches, an optical binary symmetric logic module (OBSLM) is
      experimentally implemented. The applications of the OBSLM to optical digital,
      symbolic, and neural computing are discussed.

PMID- 19746153
TI  - Ring expansion of substituted norbornadienes for the synthesis of mono- and
      disubstituted 2-azabicyclo[3.2.1]octadienes.
AB  - We have studied the conversion of substituted norbornadienes into a substituted 2
      azabicyclo[3.2.1]octadiene system via reaction with toluenesulfonyl azide. We
      have found that both and mono- and disubstituted norbornadienes will undergo the
      cycloaddition/rearrangement sequence to provide the bicyclooctadiene ring system
      as a single regioisomer. The 2-azabicyclo[3.2.1]octane ring system can be
      prepared from the unsaturated 2-azabicyclo[3.2.1]octadiene ring system.

PMID- 19746154
TI  - C-Galactosylceramide Diastereomers via Sharpless Asymmetric Epoxidation
      Chemistry.

PMID- 19746155
TI  - Addressing reported pro-apoptotic functions of NF-kappaB: targeted inhibition of
      canonical NF-kappaB enhances the apoptotic effects of doxorubicin.
AB  - The ability of the transcription factor NF-kappaB to upregulate anti-apoptotic
      proteins has been linked to the chemoresistance of solid tumors to standard
      chemotherapy. In contrast, recent studies have proposed that, in response to
      doxorubicin, NF-kappaB can be pro-apoptotic through repression of anti-apoptotic
      target genes. However, there is little evidence analyzing the outcome of NF
      kappaB inhibition on the cytotoxicity of doxorubicin in studies describing pro
      apoptotic NF-kappaB activity. In this study, we further characterize the
      activation of NF-kappaB in response to doxorubicin and evaluate its role in
      chemotherapy-induced cell death in sarcoma cells where NF-kappaB is reported to
      be pro-apoptotic. Doxorubicin treatment in U2OS cells induced canonical NF-kappaB
      activity as evidenced by increased nuclear accumulation of phosphorylated p65 at
      serine 536 and increased DNA-binding activity. Co-treatment with a small molecule
      IKKbeta inhibitor, Compound A, abrogated this response. RT-PCR evaluation of anti
      apoptotic gene expression revealed that doxorubicin-induced transcription of
      cIAP2 was inhibited by Compound A, while doxorubicin-induced repression of other
      anti-apoptotic genes was unaffected by Compound A or siRNA to p65. Furthermore,
      the combination of doxorubicin and canonical NF-kappaB inhibition with Compound A
      or siRNA to p65 resulted in decreased cell viability measured by trypan blue
      staining and MTS assay and increased apoptosis measured by cleaved poly (ADP
      ribose) polymerase and cleaved caspase 3 when compared to doxorubicin alone. Our
      results demonstrate that doxorubicin-induced canonical NF-kappaB activity
      associated with phosphorylated p65 is anti-apoptotic in its function and that
      doxorubicin-induced repression of anti-apoptotic genes occurs independent of p65.
      Therefore, combination therapies incorporating NF-kappaB inhibitors together with
      standard chemotherapies remains a viable method to improve the clinical outcomes
      in patients with advanced stage malignancies.

PMID- 19746156
TI  - Cyclophosphamide chemotherapy sensitizes tumor cells to TRAIL-dependent CD8 T
      cell-mediated immune attack resulting in suppression of tumor growth.
AB  - BACKGROUND: Anti-cancer chemotherapy can be simultaneously lymphodepleting and
      immunostimulatory. Pre-clinical models clearly demonstrate that chemotherapy can
      synergize with immunotherapy, raising the question how the immune system can be
      mobilized to generate anti-tumor immune responses in the context of chemotherapy.
      METHODS AND FINDINGS: We used a mouse model of malignant mesothelioma, AB1-HA, to
      investigate T cell-dependent tumor resolution after chemotherapy. Established AB1
      HA tumors were cured by a single dose of cyclophosphamide in a CD8 T cell- and NK
      cell-dependent manner. This treatment was associated with an IFN-alpha/beta
      response and a profound negative impact on the anti-tumor and total CD8 T cell
      responses. Despite this negative effect, CD8 T cells were essential for curative
      responses. The important effector molecules used by the anti-tumor immune
      response included IFN-gamma and TRAIL. The importance of TRAIL was supported by
      experiments in nude mice where the lack of functional T cells could be
      compensated by agonistic anti-TRAIL-receptor (DR5) antibodies. CONCLUSION: The
      data support a model in which chemotherapy sensitizes tumor cells for T cell-,
      and possibly NK cell-, mediated apoptosis. A key role of tumor cell sensitization
      to immune attack is supported by the role of TRAIL in tumor resolution and
      explains the paradox of successful CD8 T cell-dependent anti-tumor responses in
      the absence of CD8 T cell expansion.

PMID- 19746158
TI  - Neuropsychological sequelae of carotid angioplasty with stent placement:
      correlation with ischemic lesions in diffusion weighted imaging.
AB  - BACKGROUND AND PURPOSE: Few studies investigated the neuropsychological outcome
      after carotid angioplasty with stent placement (CAS), yielding partially
      inconsistent results. The present investigation evaluated the effect of CAS in
      patients with high-grade stenosis and assessed the predictive value of ischemic
      lesion number for postinterventional cognitive deterioration. METHODS: 22
      patients were tested neuropsychologically before and six weeks after CAS.
      Cerebral ischemic changes were assessed with diffusion weighted imaging (DWI)
      prior to and after angioplasty. RESULTS: Pre- to postinterventional cognitive
      performance improved significantly in terms of verbal memory (t = -2.30; p<0.05),
      whereas significant deterioration was noted regarding verbal memory span (t =
      2.31; p<0.05). 8 (36%) persons conformed to the criteria of cognitive
      improvement. 6 patients (27%) were postinterventionally classified as having
      deficits. Analysis yielded no statistically significant correlations between
      lesion quantity and cognitive change. CONCLUSION: Both improvement and
      deterioration of cognitive functioning was observed in our collective of
      patients, leaving the neuropsychological outcome after percutaneous transluminal
      angioplasty unpredictable in individual cases. The presence of acute ischemic
      lesions on DWI was found to be not tightly associated with cognitive dysfunction
      after CAS.

PMID- 19746157
TI  - Metabolic flux analysis of mitochondrial uncoupling in 3T3-L1 adipocytes.
AB  - BACKGROUND: Increasing energy expenditure at the cellular level offers an
      attractive option to limit adiposity and improve whole body energy balance. In
      vivo and in vitro observations have correlated mitochondrial uncoupling protein-1
      (UCP1) expression with reduced white adipose tissue triglyceride (TG) content.
      The metabolic basis for this correlation remains unclear. METHODOLOGY/PRINCIPAL
      FINDINGS: This study tested the hypothesis that mitochondrial uncoupling requires
      the cell to compensate for the decreased oxidation phosphorylation efficiency by
      up-regulating lactate production, thus redirecting carbon flux away from TG
      synthesis. Metabolic flux analysis was used to characterize the effects of non
      lethal, long-term mitochondrial uncoupling (up to 18 days) on the pathways of
      intermediary metabolism in differentiating 3T3-L1 adipocytes. Uncoupling was
      induced by forced expression of UCP1 and chemical (FCCP) treatment. Chemical
      uncoupling significantly decreased TG content by ca. 35%. A reduction in the ATP
      level suggested diminished oxidative phosphorylation efficiency in the uncoupled
      adipocytes. Flux analysis estimated significant up-regulation of glycolysis and
      down-regulation of fatty acid synthesis, with chemical uncoupling exerting
      quantitatively larger effects. CONCLUSIONS/SIGNIFICANCE: The results of this
      study support our hypothesis regarding uncoupling-induced redirection of carbon
      flux into glycolysis and lactate production, and suggest mitochondrial proton
      translocation as a potential target for controlling adipocyte lipid metabolism.

PMID- 19746159
TI  - The formin-homology protein SmDia interacts with the Src kinase SmTK and the
      GTPase SmRho1 in the gonads of Schistosoma mansoni.
AB  - BACKGROUND: Schistosomiasis (bilharzia) is a parasitic disease of worldwide
      significance affecting human and animals. As schistosome eggs are responsible for
      pathogenesis, the understanding of processes controlling gonad development might
      open new perspectives for intervention. The Src-like tyrosine-kinase SmTK3 of
      Schistosoma mansoni is expressed in the gonads, and its pharmacological
      inhibition reduces mitogenic activity and egg production in paired females in
      vitro. Since Src kinases are important signal transduction proteins it is of
      interest to unravel the signaling cascades SmTK3 is involved in to understand its
      cellular role in the gonads. METHODOLOGY AND RESULTS: Towards this end we
      established and screened a yeast two-hybrid (Y2H) cDNA library of adult S.
      mansoni with a bait construct encoding the SH3 (src homology) domain and unique
      site of SmTK3. Among the binding partners found was a diaphanous homolog (SmDia),
      which was characterized further. SmDia is a single-copy gene transcribed
      throughout development with a bias towards male transcription. Its deduced amino
      acid sequence reveals all diaphanous-characteristic functional domains. Binding
      studies with truncated SmDia clones identified SmTK3 interaction sites
      demonstrating that maximal binding efficiency depends on the N-terminal part of
      the FH1 (formin homology) domain and the inter-domain region of SmDia located
      upstream of FH1 in combination with the unique site and the SH3 domain of SmTK3,
      respectively. SmDia also directly interacted with the GTPase SmRho1 of S.
      mansoni. In situ hybridization experiments finally demonstrated that SmDia,
      SmRho1, and SmTK3 are transcribed in the gonads of both genders. CONCLUSION:
      These data provide first evidence for the existence of two cooperating pathways
      involving Rho and Src that bridge at SmDia probably organizing cytoskeletal
      events in the reproductive organs of a parasite, and beyond that in gonads of
      eukaryotes. Furthermore, the FH1 and inter domain region of SmDia have been
      discovered as binding sites for the SH3 and unique site domains of SmTK3,
      respectively.

PMID- 19746160
TI  - Effects of chronic mild stress on the development of atherosclerosis and
      expression of toll-like receptor 4 signaling pathway in adolescent apolipoprotein
      E knockout mice.
AB  - Here, we investigated the effect of chronic mild stress (CMS) on the development
      of atherosclerosis as well as the expression of Toll-like receptors (TLRs)
      signaling pathway in adolescent apolipoprotein E knockout (apoE-/-) mice. Mice
      were subjected to daily CMS for 0, 4, and 12 weeks, respectively. To identify the
      expression of Toll-like receptor 4 signaling pathway in adolescent apolipoprotein
      E knockout mice subjected to CMS, we compared gene expression in aortas of
      stressed and unstressed mice using TLRs signaling pathway real-time PCR
      microarrays consisting of 87 genes. We found that atherosclerosis lesions both in
      aortic tress and sinuses of CMS mice were significantly increased linearly in
      response to duration of CMS exposure. Among 87 genes analyzed, 15 genes were
      upregulated in stressed mice, especially TLR4, myeloid differentiation factor 88
      (MyD88), and IL-1beta, and 28 genes were downregulated compared with nonstressed
      mice. CMS mice demonstrated markedly increased aortic atherosclerosis that were
      associated with significant increases in levels of expression of TLR4, MyD88,
      nuclear factor kappaB (NF-kappaB), MCP-1, IL-1beta, TNF-alpha, and sICAM-1. Taken
      together, our results suggest an important role for TLR4 signaling pathway in
      atherosclerosis in a CMS mouse model.

PMID- 19746161
TI  - Synthetic morphology using alternative inputs.
AB  - Designing the shape and size of a cell is an interesting challenge for synthetic
      biology. Prolonged exposure to the mating pheromone alpha-factor induces an
      unusual morphology in yeast cells: multiple mating projections. The goal of this
      work was to reproduce the multiple projections phenotype in the absence of alpha
      factor using a gain-of-function approach termed "Alternative Inputs (AIs)". An
      alternative input is defined as any genetic manipulation that can activate the
      signaling pathway instead of the natural input. Interestingly, none of the
      alternative inputs were sufficient to produce multiple projections although some
      produced a single projection. Then, we extended our search by creating all
      combinations of alternative inputs and deletions that were summarized in an AIs
      Deletions matrix. We found a genetic manipulation (AI-Ste5p ste2Delta) that
      enhanced the formation of multiple projections. Following up this lead, we
      demonstrated that AI-Ste4p and AI-Ste5p were sufficient to produce multiple
      projections when combined. Further, we showed that overexpression of a membrane
      targeted form of Ste5p alone could also induce multiple projections. Thus, we
      successfully re-engineered the multiple projections mating morphology using
      alternative inputs without alpha-factor.

PMID- 19746162
TI  - The effect of growth conditions on the seed size/number trade-off.
AB  - BACKGROUND: If the amount of resources allocated to reproduction (K) is fixed,
      then an increase in seed mass (S) can only be achieved by a decrease in seed
      number (n = K/S). Thus, log(n) = log(K)-log(S) producing a slope of -1 when seed
      mass and number are plotted on log-log axes. However, in comparative studies,
      empirical support for a slope of -1 is limited and contentious, leading some to
      question the utility of this concept. METHODOLOGY/PRINCIPAL FINDINGS: First, we
      show that the expected slope depends on whether genotypes and species producing
      seeds of different mass are expected to reach the same adult size and that this
      in turn depends partly on the nature of growth. Second, we present experimental
      results using a population of recombinant inbred lines (RILs) of Arabidopsis
      thaliana. When these RILs are grown in large pots with plentiful nutrients, they
      exhibit a trade-off between seed size and number with a slope of -1.68 (+/-0.18)
      on log-log axes. This occurs because of genetic correlations between seed mass
      and adult size so that, under the right growth conditions, lines producing
      lighter seeds have the genetic potential to produce larger rosettes and hence a
      greater total mass of seeds. We re-grew lines in small pots (10 and 40 mm
      diameter) in a nutrient-poor substrate so that final adult size was heavily
      restricted by pot size. CONCLUSIONS/SIGNIFICANCE: Under our growth conditions,
      small-seeded lines were unable to produce a greater total mass of seeds. Hence a
      trade-off emerged between seed mass and seed number with a slope of -1.166+/
      0.319 on log-log axes in 40-mm diameter pots (close to the expected value of -1),
      although the slope was 0.132+/-0.263 in 10-mm diameter pots, demonstrating that
      the nature of the trade-off is sensitive to the growth conditions.

PMID- 19746163
TI  - Ancient Leishmaniasis in a highland desert of Northern Chile.
AB  - BACKGROUND: Leishmaniasis is an infectious disease endemic today in many areas of
      South America. METHODOLOGY: We discovered morphologic and molecular evidence of
      ancient infections in 4 female skulls in the archaeological cemetery of Coyo
      Oriente, in the desert of San Pedro de Atacama, Northern Chile. The boney facial
      lesions visible in the skulls could have been caused by a number of chronic
      infections including chronic Leishmaniasis. This diagnosis was confirmed using
      PCR-sequenced analyses of bone fragments from the skulls of the affected
      individuals.Leishmaniasis is not normally found in the high-altitude desert of
      Northern Chile; where the harsh climate does not allow the parasite to complete
      its life cycle. The presence of Leishmaniasis in ancient skulls from the region
      implies infection by the protozoan in an endemic area-likely, in our subjects, to
      have been the lowlands of North-Eastern Argentina or in Southern Bolivia.
      CONCLUSIONS: We propose that the presence of the disease in ancient times in the
      high altitude desert of San Pedro de Atacama is the result of an exogamic system
      of patrilocal marriages, where women from different cultures followed their
      husbands to their ancestral homes, allowing immigrant women, infected early in
      life, to be incorporated in the Atacama desert society before they became
      disfigured by the disease. The present globalization of goods and services and
      the extraordinary facile movement of people across borders and continents have
      lead to a resurgence of infectious diseases and re-emergence of infections such
      as Leishmaniasis. We show here that such factors were already present millennia
      ago, shaping demographic trends and the epidemiology of infections just as they
      do today.

PMID- 19746164
TI  - Implications of storing urinary DNA from different populations for molecular
      analyses.
AB  - BACKGROUND: Molecular diagnosis using urine is established for many sexually
      transmitted diseases and is increasingly used to diagnose tumours and other
      infectious diseases. Storage of urine prior to analysis, whether due to home
      collection or bio-banking, is increasingly advocated yet no best practice has
      emerged. Here, we examined the stability of DNA in stored urine in two
      populations over 28 days. METHODOLOGY: Urine from 40 (20 male) healthy volunteers
      from two populations, Italy and Zambia, was stored at four different temperatures
      (RT, 4 degrees C, -20 degrees C & -80 degrees C) with and without EDTA
      preservative solution. Urines were extracted at days 0, 1, 3, 7 and 28 after
      storage. Human DNA content was measured using multi-copy (ALU J) and single copy
      (TLR2) targets by quantitative real-time PCR. Zambian and Italian samples
      contained comparable DNA quantity at time zero. Generally, two trends were
      observed during storage; no degradation, or rapid degradation from days 0 to 7
      followed by little further degradation to 28 days. The biphasic degradation was
      always observed in Zambia regardless of storage conditions, but only twice in
      Italy. CONCLUSION: Site-specific differences in urine composition significantly
      affect the stability of DNA during storage. Assessing the quality of stored urine
      for molecular analysis, by using the type of strategy described here, is
      paramount before these samples are used for molecular prognostic monitoring,
      genetic analyses and disease diagnosis.

PMID- 19746165
TI  - Comparative proteomic analysis of the PhoP regulon in Salmonella enterica serovar
      Typhi versus Typhimurium.
AB  - BACKGROUND: S. Typhi, a human-restricted Salmonella enterica serovar, causes a
      systemic intracellular infection in humans (typhoid fever). In comparison, S.
      Typhimurium causes gastroenteritis in humans, but causes a systemic typhoidal
      illness in mice. The PhoP regulon is a well studied two component (PhoP/Q)
      coordinately regulated network of genes whose expression is required for
      intracellular survival of S. enterica. METHODOLOGY/PRINCIPAL FINDINGS: Using high
      performance liquid chromatography mass spectrometry (HPLC-MS/MS), we examined the
      protein expression profiles of three sequenced S. enterica strains: S.
      Typhimurium LT2, S. Typhi CT18, and S. Typhi Ty2 in PhoP-inducing and non
      inducing conditions in vitro and compared these results to profiles of phoP(-)/Q(
      ) mutants derived from S. Typhimurium LT2 and S. Typhi Ty2. Our analysis
      identified 53 proteins in S. Typhimurium LT2 and 56 proteins in S. Typhi that
      were regulated in a PhoP-dependent manner. As expected, many proteins identified
      in S. Typhi demonstrated concordant differential expression with a homologous
      protein in S. Typhimurium. However, three proteins (HlyE, STY1499, and CdtB) had
      no homolog in S. Typhimurium. HlyE is a pore-forming toxin. STY1499 encodes a
      stably expressed protein of unknown function transcribed in the same operon as
      HlyE. CdtB is a cytolethal distending toxin associated with DNA damage, cell
      cycle arrest, and cellular distension. Gene expression studies confirmed up
      regulation of mRNA of HlyE, STY1499, and CdtB in S. Typhi in PhoP-inducing
      conditions. CONCLUSIONS/SIGNIFICANCE: This study is the first protein expression
      study of the PhoP virulence associated regulon using strains of Salmonella mutant
      in PhoP, has identified three Typhi-unique proteins (CdtB, HlyE and STY1499) that
      are not present in the genome of the wide host-range Typhimurium, and includes
      the first protein expression profiling of a live attenuated bacterial vaccine
      studied in humans (Ty800).

PMID- 19746166
TI  - The 3' region of the chicken hypersensitive site-4 insulator has properties
      similar to its core and is required for full insulator activity.
AB  - Chromatin insulators separate active transcriptional domains and block the spread
      of heterochromatin in the genome. Studies on the chicken hypersensitive site-4
      (cHS4) element, a prototypic insulator, have identified CTCF and USF-1/2 motifs
      in the proximal 250 bp of cHS4, termed the "core", which provide enhancer
      blocking activity and reduce position effects. However, the core alone does not
      insulate viral vectors effectively. The full-length cHS4 has excellent insulating
      properties, but its large size severely compromises vector titers. We performed a
      structure-function analysis of cHS4 flanking lentivirus-vectors and analyzed
      transgene expression in the clonal progeny of hematopoietic stem cells and
      epigenetic changes in cHS4 and the transgene promoter. We found that the core
      only reduced the clonal variegation in expression. Unique insulator activity
      resided in the distal 400 bp cHS4 sequences, which when combined with the core,
      restored full insulator activity and open chromatin marks over the transgene
      promoter and the insulator. These data consolidate the known insulating activity
      of the canonical 5' core with a novel 3' 400 bp element with properties similar
      to the core. Together, they have excellent insulating properties and viral
      titers. Our data have important implications in understanding the molecular basis
      of insulator function and design of gene therapy vectors.

PMID- 19746167
TI  - Immunolocalization of proteoglycans in Meckel's cartilage of the rat.
AB  - The aim of this study was to investigate the presence and distribution of
      proteoglycans within Meckel's cartilage of rat embryos. A standard indirect
      immunoperoxidase technique was used on paraffin sections of rat heads. Sections
      were incubated with monoclonal antibodies recognising core protein epitopes in
      the proteoglycans versican and CD44. Polyclonal antibodies localized the
      proteoglycans decorin, biglycan and lumican. Versican was expressed by
      chondrocytes, but very weekly by the extracellular matrix. Decorin was strongly
      expressed by both of chondrocytes and the ECM. Both of biglycan and lumican were
      moderately expressed by chondrocytes, but weakly by the extracellular matrix.
      CD44 was weakly expressed by chondrocytes only, without staining of the ECM. It
      is concluded that Meckel's cartilage chondrocytes express the proteoglycans
      versican, decorin, biglycan, lumican and CD44 at variable levels during
      development in the rat. Such data are important for a greater understanding of
      the changes that take place during mandibular development. Further studies are
      needed to elucidate the exact role of proteoglycans during Meckel's cartilage and
      mandibular organogenesis.

PMID- 19746168
TI  - Biochemical characterization of bovine brain myristoyl-CoA:protein N
      myristoyltransferase type 2.
AB  - Protein N-myristoylation is a lipidic modification which refers to the covalent
      attachment of myristate, a 14-carbon saturated fatty acid, to the N-terminal
      glycine residue of a number of mammalian, viral, and fungal proteins. In this
      paper, we have cloned the gene coding for myristoyl-CoA:protein N
      myristoyltransferase (NMT) from Bos tarus brain. The open reading frame codes for
      a 410-amino-acid protein and overexpressed in Escherichia coli. Kinetic studies
      suggested that bovine brain NMT2 and human NMT1 show significant differences in
      their peptide substrate specificities. The metal ion Ca(2+) had stimulatory
      effects on NMT2 activity while Mn(2+) and Zn(2+) inhibited the enzyme activity.
      In addition, NMT2 activity was inhibited by various organic solvents and other
      detergents while NMT1 had a stimulatory effect. Biochemical characterization
      suggested that both forms of NMT have unique characteristics. Further analysis
      towards functional role NMT2 will lead the development of therapeutic target for
      the progression of various diseases such as cancer, cardiovascular diseases, and
      neurodegenerative diseases.

PMID- 19746169
TI  - Relationship between estradiol and antioxidant enzymes activity of ischemic
      stroke.
AB  - Some evidence suggests the neuroprotection of estrogen provided by the
      antioxidant activity of this compound. The main objective of this study was to
      determine the level of estradiol and its correlation with the activity of
      antioxidant enzymes, total antioxidant status and ferritin from ischemic stroke
      subjects. The study population consisted of 30 patients with acute ischemic
      stroke and 30 controls. There was no significant difference between estradiol in
      stroke and control group. The activity of superoxide dismutase and level of
      ferritin was higher in stroke compared with control group (P < .05, P < .001,
      resp.). There was no significant correlation between estradiol and glutathione
      peroxidase, glutathione reductase, catalase, total antioxidant status, and
      ferritin in stroke and control groups. We observed inverse correlation between
      estradiol with superoxide dismutase in males of stroke patients (r = -0.54, P =
      .029). Our results supported that endogenous estradiol of elderly men and women
      of stroke or control group has no antioxidant activity.

PMID- 19746170
TI  - Subcutaneous vs Submuscular Ulnar Nerve Transposition in Moderate Cubital Tunnel
      Syndrome.
AB  - BACKGROUND: The surgical treatment of Cubital tunnel syndrome (CubTS) is still a
      matter of debate. No consensus exists about the necessity of anterior
      transposition of the ulnar nerve after decompression. However, this technique is
      fairly common in clinical practice. MATERIAL AND METHODOLOGY: In the present
      study we compared the operative technique (incision length, operative time),
      postoperative care (postoperative pain and complications) and the outcome between
      subcutaneous transposition and submuscular transposition of the ulnar nerve as
      two surgical modalities in treating moderate CubTS. Between March 2004 and March
      2007, twenty six patients with moderate CubTS (according to Dellon's grading
      system) were stratified according to age and gender into these two surgical
      techniques. The two groups were prospectively followed up 2 weeks, 6 months and
      12 months postoperatively by the same observer and the operation outcome was
      assessed using the Bishop rating system. RESULTS: We found that the subcutaneous
      transposition of the ulnar nerve was associated with shorter incision, shorter
      operative time, less postoperative pain, less postoperative complication and
      better outcome compared with the submuscular transposition. CONCLUSION: The
      authors recommend the subcutaneous technique when considering anterior
      transposition of the ulnar nerve in treating moderate CubTS.

PMID- 19746171
TI  - Complete avulsion of the extensor mechanism of a finger with simultaneous
      dislocation of the proximal interphalangeal joint.
AB  - We report a rare case of open dislocation of the proximal interphalangeal (PIP)
      joint, associated with simultaneous avulsion of the central band and distal
      insertion of the extensor mechanism, rapture of the proximal volar plate, and
      rapture of the ulnar collateral ligament of the PIP joint.Although isolated IP
      joint injuries are common, they rarely occur simultaneously in a single finger.
      Even more rarely are they accompanied by a complete avulsion of the extensor
      mechanism. Operative restoration of the injured structures is a necessity in
      order to achieve a good functional outcome.An initial forceful flexion of the
      finger resulting to rapture of the extensor apparatus and then followed by finger
      hyperextension and PIP joint dislocation is our perception of the possible
      mechanism of this extremely rare injury.

PMID- 19746172
TI  - Inhibition of glutathione and thioredoxin metabolism enhances sensitivity to
      perifosine in head and neck cancer cells.
AB  - The hypothesis that the Akt inhibitor, perifosine (PER), combined with inhibitors
      of glutathione (GSH) and thioredoxin (Trx) metabolism will induce cytotoxicity
      via metabolic oxidative stress in human head and neck cancer (HNSCC) cells was
      tested. PER induced increases in glutathione disulfide (%GSSG) in FaDu, Cal-27,
      and SCC-25 HNSCCs as well as causing significant clonogenic cell killing in FaDu
      and Cal-27, which was suppressed by simultaneous treatment with N-acetylcysteine
      (NAC). An inhibitor of GSH synthesis, buthionine sulfoximine (BSO), sensitized
      Cal-27 and SCC-25 cells to PER-induced clonogenic killing as well as decreased
      total GSH and increased %GSSG. Additionally, inhibition of thioredoxin reductase
      activity (TrxRed) with auranofin (AUR) was able to induce PER sensitization in
      SCC-25 cells that were initially refractory to PER. These results support the
      conclusion that PER induces oxidative stress and clonogenic killing in HNSCC
      cells that is enhanced with inhibitors of GSH and Trx metabolism.

PMID- 19746173
TI  - The incidence and management of pleural injuries occurring during open
      nephrectomy.
AB  - OBJECTIVE: To evaluate the incidence, management, and risk factors of pleural
      injuries occurring during open nephrectomy. METHODS: Between June 2004/and June
      2008, 165 patients (167 renal units) underwent open simple (n = 37, 22.2%),
      partial (n = 39, 23.4%) or radical (n = 91, 54.5%) nephrectomy in our
      institution. RESULTS: Flank, Chevron, and abdominal midline incisions were used
      in 148(88.6%), 17(10.2%), and in 2(1.2%) surgical procedures, respectively. Ribs
      were excised in 109(65.3%) procedures (11th rib, 10th-11th ribs, and 11th-12th
      ribs). Intraoperative pleural injuries were detected in 20(12%) procedures,
      16(80%) were treated successfully with simple evacuation technique, and 4
      required chest tube insertion. Age, sex, surgery type, incision type, and surgery
      site were not associated with pleural injury occurrence (P > .05). Rib resection
      was the only parameter associated with pleural injury occurrence. CONCLUSION:
      Pleural injuries occur in 12% of open nephrectomy procedures, and 80% can be
      repaired successfully. Few of them (2.4%) need chest tube insertion. Performing
      rib resection is a significant risk factor for pleural injury occurrence during
      nephrectomies.

PMID- 19746174
TI  - Virtual Screening as a Technique for PPAR Modulator Discovery.
AB  - Virtual screening (VS) is a discovery technique to identify novel compounds with
      therapeutic and preventive efficacy against disease. Our current focus is on the
      in silico screening and discovery of novel peroxisome proliferator-activated
      receptor-gamma (PPARgamma) agonists. It is well recognized that PPARgamma
      agonists have therapeutic applications as insulin sensitizers in type 2 diabetes
      or as anti-inflammatories. VS is a cost- and time-effective means for identifying
      small molecules that have therapeutic potential. Our long-term goal is to devise
      computational approaches for testing the PPARgamma-binding activity of extensive
      naturally occurring compound libraries prior to testing agonist activity using
      ligand-binding and reporter assays. This review summarizes the high potential for
      obtaining further fundamental understanding of PPARgamma biology and development
      of novel therapies for treating chronic inflammatory diseases through evolution
      and implementation of computational screening processes for immunotherapeutics in
      conjunction with experimental methods for calibration and validation of results.

PMID- 19746175
TI  - Synthesis, spectroscopic and thermal characterization of copper(II) and iron(III)
      complexes of folic acid and their absorption efficiency in the blood.
AB  - The absorption efficiency of any drug in blood is of prime importance. Compounds
      having the general formula: K(n)[M(FO)(2)(H(2)O)(2)] . xH(2)O, where (M = Cu(II)
      or Fe(III), n = 2 or 1, FO = folate anion, x = 2 or 3 with respect), were
      prepared, and their absorption efficiency in rodent's blood was determined. The
      obtained compounds were characterized by elemental analysis, infrared as well as
      thermogravimetric analysis and polarization of light. The results suggest that
      the two folate complexes were formed in 1 : 2 molar ratio (metal : folic acid)
      which acted as a bidentate ligand through both carboxylic groups. Polarization of
      light proved that the folate complexes have symmetric geometry. Biological
      application proved that Cu(II) and Fe(III) complexes were absorbed more
      efficiently in rodent blood than folic acid itself.

PMID- 19746177
TI  - Cardiac sarcoidosis culminating in severe biventricular failure.
AB  - A 59-year-old woman with a history of lung sarcoidosis developed general edema
      and exertional dyspnea. An electrocardiogram showed first-degree atrioventricular
      block with complete right bundle branch block. Chest X-ray showed cardiomegaly.
      Echocardiography showed diffuse and severe hypokinesis of the left ventricle (LV)
      and biventricular enlargement with severe tricuspid regurgitation. Myocardial
      scintigraphy disclosed a perfusion defect at the ventricular septum and
      hypoperfusion at the posterior wall and the apex. On cardiac catheterization,
      pulmonary capillary wedge pressure, right ventricular, and right atrial pressures
      were elevated. Coronary angiograms were normal. Myocardial biopsy of the right
      ventricle histologically revealed epithelioid cell granuloma with infiltration of
      fibrous cells. The patient's symptom and LV function were improved with
      conventional medical therapy for heart failure. This is a rare case of cardiac
      sarcoidosis resulting in biventricular failure.

PMID- 19746176
TI  - Anti-hepatitis B virus X protein in sera is one of the markers of development of
      liver cirrhosis and liver cancer mediated by HBV.
AB  - Hepatitis B virus X protein (HBx) plays a crucial role in the development of
      hepatocellular carcinoma (HCC). However, the significance of circulating antibody
      to hepatitis B virus X antigen (anti-HBx) in sera remains unclear. In the present
      study, we examined the titers of anti-HBx (IgG) in the sera from 173 patients
      with chronic hepatitis B (CHB), 106 liver cirrhosis (LC), and 61 HCC by enzyme
      linked immunosorbent assay (ELISA), respectively. Our data showed that the
      positive rates of anti-HBx were higher in sera of LC (40.6%) and HCC (34.4%) than
      those of CHB (10.4%), P < .05. In all 40 patients with anti-HBx+ out of 340
      patients, 39 (97.5%) were HBsAg/HBeAg/anti-HBc+ and 1 (2.5%) was anti-HBs+ (P <
      .01), suggesting that anti-HBx in sera is a marker of HBV replication rather than
      a protective antibody. Thus, our findings reveal that circulating anti-HBx in
      sera is one of the markers of development of LC and HCC mediated by HBV.

PMID- 19746178
TI  - Palliation with oesophageal metal stent of pseudoachalasia from gastric carcinoma
      at the cardia: a case report.
AB  - We present an 82-year-old woman with a 3-month history of progressive dysphagia
      and a normal initial upper gastrointestinal endoscopy. The diagnosis of
      pseudoachalasia was suspected by oesophageal manometric and barium swallow
      studies, and confirmed by biopsies revealing an intestinal type carcinoma of the
      stomach at a repeated endoscopy. In view of the history of heart disease,
      diabetes, and old age, this patient was treated by a partially covered Ultraflex
      self-expanding metal stent (Boston Scientific, Natick, MA, USA) placed into the
      oesophageal body with no direct complications and obtaining the relief from
      dysphagia. During the 11-month follow-up she was treated for an iron deficiency
      anaemia due to reflux oesophagitis with ulcerations in the oesophageal body and
      died from myocardial infarction. According to the localization of the cancer, the
      old age, and the presence of comorbidities, we should recommend the insertion of
      a partially covered self-expanding metal stent as a reasonable palliative
      treatment in selected subjects with pseudoachalasia.

PMID- 19746179
TI  - Trace lead measurement and online removal of matrix interference in geosamples by
      ion-exchange coupled with flow injection and hydride generation atomic
      fluorescence spectrometry.
AB  - A flow injection method has been developed for the direct determination of free
      available Pb(II). The method is based on the chemical sorption of Pb(II), from
      pH7 solutions, on a column packed of chelating resin. The retained complex was
      afterwards eluted with hydrochloric acid followed by hydride generation with
      reduction by tetrahydroborate. The preconcentration system proposed in this paper
      allows the elimination of great part of the saline content in the sample. A
      thorough scrutiny was made for chemical variables and FI parameters. With a
      sampling volume of 10.5 mL, quantitative retention of Pb (II) was obtained, along
      with an enrichment factor of 40 and a sampling frequency of 15 h(-1). The
      detection limit, defined as 3 times the blank standard deviation (3sigma), was
      0.0031 ngml(-1). The precision was characterized by an RSD value of 3.78% (at the
      4 ng.ml(-1) level, n = 11). The developed method has been applied to the
      determination of trace Pb in three standard reference materials. Accuracy was
      assessed through comparing the results with the accepted values.

PMID- 19746180
TI  - Impaired perinatal growth and longevity: a life history perspective.
AB  - Life history theory proposes that early-life cues induce highly integrated
      responses in traits associated with energy partitioning, maturation,
      reproduction, and aging such that the individual phenotype is adaptively more
      appropriate to the anticipated environment. Thus, maternal and/or neonatally
      derived nutritional or endocrine cues suggesting a threatening environment may
      favour early growth and reproduction over investment in tissue reserve and repair
      capacity. These may directly affect longevity, as well as prioritise insulin
      resistance and capacity for fat storage, thereby increasing susceptibility to
      metabolic dysfunction and obesity. These shifts in developmental trajectory are
      associated with long-term expression changes in specific genes, some of which may
      be underpinned by epigenetic processes. This normative process of developmental
      plasticity may prove to be maladaptive in human environments in transition
      towards low extrinsic mortality and energy-dense nutrition, leading to the
      development of an inappropriate phenotype with decreased potential for longevity
      and/or increased susceptibility to metabolic disease.

PMID- 19746181
TI  - Robust and unbiased variance of GLM coefficients for misspecified autocorrelation
      and hemodynamic response models in fMRI.
AB  - As a consequence of misspecification of the hemodynamic response and noise
      variance models, tests on general linear model coe cients are not valid. Robust
      estimation of the variance of the general linear model (GLM) coecients in fMRI
      time series is therefore essential. In this paper an alternative method to
      estimate the variance of the GLM coe cients accurately is suggested and compared
      to other methods. The alternative, referred to as the sandwich, is based
      primarily on the fact that the time series are obtained from multiple
      exchangeable stimulus presentations. The analytic results show that the sandwich
      is unbiased. Using this result, it is possible to obtain an exact statistic which
      keeps the 5% false positive rate. Extensive Monte Carlo simulations show that the
      sandwich is robust against misspeci cation of the autocorrelations and of the
      hemodynamic response model. The sandwich is seen to be in many circumstances
      robust, computationally efficient, and flexible with respect to correlation
      structures across the brain. In contrast, the smoothing approach can be robust to
      a certain extent but only with specific knowledge of the circumstances for the
      smoothing parameter.

PMID- 19746182
TI  - Ovarian cancer pathogenesis: a model in evolution.
AB  - Ovarian cancer is a deadly disease for which there is no effective means of early
      detection. Ovarian carcinomas comprise a diverse group of neoplasms, exhibiting a
      wide range of morphological characteristics, clinical manifestations, genetic
      alterations, and tumor behaviors. This high degree of heterogeneity presents a
      major clinical challenge in both diagnosing and treating ovarian cancer.
      Furthermore, the early events leading to ovarian carcinoma development are poorly
      understood, thus complicating efforts to develop screening modalities for this
      disease. Here, we provide an overview of the current models of ovarian cancer
      pathogenesis, highlighting recent findings implicating the fallopian tube fimbria
      as a possible site of origin of ovarian carcinomas. The ovarian cancer model will
      continue to evolve as we learn more about the genetics and etiology of this
      disease.

PMID- 19746183
TI  - MR imaging in endometrial carcinoma as a diagnostic tool for the prediction of
      myometrial invasion and lymph node metastasis.
AB  - PURPOSE: The purpose of this study was to evaluate the factors that are
      associated with the accuracy of magnetic resonance (MR) imaging for predicting
      myometrial invasion and lymph node metastasis in women with endometrial
      carcinoma. MATERIALS AND METHODS: We retrospectively reviewed the medical records
      and preoperative MR imaging reports of 128 women who had pathologically proven
      endometrial carcinoma. We compared the MR imaging and the histopathology
      findings. RESULTS: The sensitivity, specificity and accuracy for identifing any
      myometrial invasion (superficial or deep) were 0.81, 0.61 and 0.74, respectively;
      these values for deep myometrial invasion were 0.60, 0.94 and 0.86, respectively.
      The sensitivity, specificity and accuracy of MR imaging for detecting lymph node
      metastasis were 50.0%, 96.6% and 93.0%, respectively. The patients who were
      older, had more deliveries and a larger tumor size more frequently had incorrect
      prediction of deep myometrial invasion (p=0.034, p=0.044, p=0.061, respectively).
      A higher tumor grade, a histology other than the endometrioid type, myometrial
      invasion on MR findings and a larger tumor size were associated with a more
      frequent false-negative prediction of lymph node metastasis (p=0.018, p=0.017,
      p=0.002, p=0.047, respectively). A larger tumor size was also associated with
      more frequent false-positive results (p=0.009). CONCLUSIONS: There are several
      factors that make accurate assessment of myometrial invasion or lymph node
      metastasis difficult with using MRI; therefore, the patients with these factors
      should have their MR findings cautiously interpreted.

PMID- 19746184
TI  - Clinical value of new staging systems for multiple myeloma.
AB  - PURPOSE: We wanted to investigate the validity of the recently introduced
      Southwest Oncology Group (SWOG) staging system and the International Staging
      System (ISS) by comparing both systems with the widely accepted Durie/Salmon (DS)
      system for multiple myeloma patients. MATERIALS AND METHODS: Between 1992 and
      2005, 85 multiple myeloma patients (men: women 41:44, median age: 63 years
      (range: 36~87)) with available baseline values of albumin and beta(2)
      microglobulin were enrolled. The clinical and laboratory data were
      retrospectively obtained. RESULTS: According to the ISS, 11 patients were stage I
      (12.9%), 30 patients stage II (35.3%) and 44 patients stage III (51.8%). The
      median survivals of the ISS stages I, II and III were 78.6 months, 31.8 months
      and 15.1 months, respectively (p=0.015). The DS staging system was not able to
      predict the survival. For the SWOG staging system, 14 patients were stage I
      (16.4%), 27 patients stage II (31.8%), 27 patients stage III (31.8%) and 17
      patients were stage IV (20.0%). The median survivals of the SWOG staging system
      stage I, II, III and IV were 78.6 months, 31.8 months, 11.6 months and 24.8
      months, respectively (p=0.0075). CONCLUSION: The ISS staging system showed better
      reliability, simplicity and predictability for survival than the DS and SWOG
      staging systems for multiple myeloma patients.

PMID- 19746185
TI  - Optimization and limitation of calcium ionophore to generate DCs from acute
      myeloid leukemic cells.
AB  - PURPOSE: Calcium ionophore (CI) is used to generate dendritic cells (DCs) from
      progenitor cells, monocytes, or leukemic cells. The aim of this study was to
      determine the optimal dose of CI and the appropriate length of cell culture
      required for acute myeloid leukemia (AML) cells and to evaluate the limitations
      associated with CI. MATERIALS AND METHODS: To generate leukemic DCs, leukemic
      cells (4x10(6) cells) from six AML patients were cultured with various
      concentrations of CI and/or IL-4 for 1, 2 or 3 days. RESULTS: Potent leukemic DCs
      were successfully generated from all AML patients, with an average number of
      1.2x10(6) cells produced in the presence of CI (270 ng/ml) for 2 days. Several
      surface molecules were clearly upregulated in AML cells supplemented with CI and
      IL-4, but not CD11c. Leukemic DCs cultured with CI had a higher allogeneic T cell
      stimulatory capacity than untreated AML cells, but the addition of IL-4 did not
      augment the MLR activity of these cells. AML cells cultured with CI in the
      presence or absence of IL-4 showed increased levels of apoptosis in comparison to
      primary cultures of AML cells. CONCLUSION: Although CI appears to be advantageous
      in terms of time and cost effectiveness, the results of the present study suggest
      that the marked induction of apoptosis by CI limits its application to the
      generation of DCs from AML cells.

PMID- 19746186
TI  - Unusual presentation of large B cell lymphoma- bone and stomach- treated with
      autologous transplantation.
AB  - Extranodal presentation of diffuse large B cell lymphoma (DLBL) is frequently
      observed in the gastrointestinal tract, CNS, bone, testes and liver. However, the
      simultaneous detection of multiple extranodal involvement at presentation is
      quite an uncommon occurrence. In this study, we report on a patient with an
      uncommon presentation of DLBL, and he had symptoms of left knee joint pain and
      hematemesis, characterized by bone and stomach involvement. Computed tomography
      and fluorodeoxyglucose-positron emission tomography (FDG-PET) scanning revealed a
      rapid, extensive spread to the bones and soft tissues. Subsequent
      histopathological examination verified the bony and gastric CD20-positive DLBL
      localization. We diagnosed this case as DLBL of stage IV with an international
      prognostic index of 3, and classified him into the high intermediate risk group.
      This patient was treated via chemotherapy with an R-CHOP regimen. After achieving
      a partial response, the patient received autologous peripheral blood stem cell
      transplantation. The patient attained partial remission, as shown on the FDG-PET
      scan, and he displayed improvement of his left femur pain.

PMID- 19746187
TI  - Palliative radiotherapy in a patient with pulmonary adenoid cystic carcinoma.
AB  - Primary adenoid cystic carcinoma in the lung is very rare, so its
      clinicopathologic characteristics have usually been extrapolated from the
      salivary disease. However, the clinical courses of pulmonary adenoid cystic
      carcinomas may be different from those of salivary disease, and individual
      differences may also exist. I report here on a case of a patient who was
      initially diagnosed as pulmonary adenoid cystic carcinoma with liver metastases
      and the tumor showed extreme radiosensitivity, but it also underwent an
      aggressive clinical course. Adenoid cystic carcinoma is usually known to be a
      slowly growing tumor, but it may rapidly disseminate, like in this patient.
      Therefore, the factors predicting aggressive behavior should be determined and
      the treatment might be individualized according to the primary sites and on the
      patient's basis.

PMID- 19746188
TI  - Thrust production and wake structure of a batoid-inspired oscillating fin.
AB  - Experiments are reported on the hydrodynamic performance of a flexible fin. The
      fin replicates some features of the pectoral fin of a batoid fish (such as a ray
      or skate) in that it is actuated in a travelling wave motion, with the amplitude
      of the motion increasing linearly along the span from root to tip. Thrust is
      found to increase with non-dimensional frequency, and an optimal oscillatory gait
      is identified. Power consumption measurements lead to the computation of
      propulsive efficiency, and an optimal efficiency condition is evaluated. Wake
      visualizations are presented, and a vortex model of the wake near zero net thrust
      is suggested. Strouhal number effects on the wake topology are also illustrated.

PMID- 19746189
TI  - Effective-substrate theory for optical reflection from a layered substrate.
AB  - We show that reflection of a monochromatic light from a semi-infinite medium
      covered with a stack of layered media is equivalent to that from an effective
      "semi-infinite medium" characterized by two distinctive optical dielectric
      constants for the s-polarized and p-polarized components, respectively. Such an
      effective-substrate approach simplifies the analysis of ellipsometry measurements
      of a wide range of surface-bound processes including thin film growth and surface
      bound reactions.

PMID- 19746190
TI  - HYPNOSIS TO MANAGE DISTRESS RELATED TO MEDICAL PROCEDURES: A META-ANALYSIS.
AB  - This meta-analysis evaluates the effect of hypnosis in reducing emotional
      distress associated with medical procedures. PsycINFO and PubMed were searched
      from their inception through February 2008. Randomized controlled trials of
      hypnosis interventions, administered in the context of clinical medical
      procedures, with a distress outcome, were included in the meta-analysis (26 of 61
      papers initially reviewed). Information on sample size, study methodology,
      participant age and outcomes were abstracted independently by 2 authors using a
      standardized form. Disagreements were resolved by consensus. Effects from the 26
      trials were based on 2342 participants. Results indicated an overall large effect
      size (ES) of 0.88 (95% CI = 0.57-1.19) in favour of hypnosis. Effect sizes
      differed significantly (p < 0.01) according to age (children benefitted to a
      greater extent than adults) and method of hypnosis delivery, but did not differ
      based on the control condition used (standard care vs. attention control).

PMID- 19746191
TI  - Synthesis, radiosynthesis and in vivo evaluation of [I]-4-(2-(bis(4
      fluorophenyl)methoxy)ethyl)-1-(4-iodobenzyl)piperidine as a selective tracer for
      imaging the dopamine transporter.
AB  - Dopamine transporter (DAT) neuroimaging is a useful tool in Parkinson's disease
      diagnosis, staging and follow-up providing information on the integrity of the
      dopaminergic neurotransmitter system in vivo. 4-(2-(Bis(4-fluorophenyl)
      methoxy)ethyl)-1-(4-iodobenzyl)piperidine (7) has nanomolar affinity for DAT and
      better selectivity over the other monoamine transporters compared with the
      existing SPECT radioligands for DAT. The aim of this study was to synthesize and
      evaluate [(123)I]-7 as an in vivo tracer for DAT.The tributylstannyl precursor
      was synthesized with an overall yield of 25%. [(123)I]-7 was synthesized by
      electrophilic destannylation with a yield of 40+/-10%. Radiochemical purity
      appeared to be >98%, whereas specific activity was at least 667 GBq/MUmol.
      Biodistribution studies in mice showed brain uptake of 0.96+/-0.53%ID/g at 30 s
      post injection (p.i.) and 0.26+/-0.02%ID/g at 3 h p.i. High blood activity was
      observed at all time points. Pretreatment with Cyclosporin A raised brain uptake
      indicating that [(123)I]-7 is transported by P-glycoprotein (P-gp) pumps. In
      rats, regional brain distribution of [(123)I]-7 was not in agreement with DAT
      distribution. These results indicate that [(123)I]-7 is not suitable for mapping
      DAT in vivo but could be a useful tracer for the P-gp transporter.

PMID- 19746192
TI  - Membrane-induced bundling of actin filaments.
AB  - Dynamic interplay between the plasma membrane and underlying cytoskeleton is
      essential for cellular shape change. Spatial organization of actin filaments,
      whose growth generates membrane deformations during motility 1, phagocytosis 2,
      endocytosis 3, and cytokinesis 4, is mediated by specific protein-protein
      interactions that branch, crosslink, and bundle filaments into networks that
      interact with the membrane. Although membrane curvature has been found to
      influence binding of proteins with curvature-sensitive domains 5, the direct
      effect of membrane elasticity on cytoskeletal network organization is not clear.
      Here we show through in vitro reconstitution and elastic modeling that a lipid
      bilayer can drive the emergence of bundled actin filament protrusions from
      branched actin filament networks, thus playing a role normally attributed to
      actin-binding proteins. Formation of these filopodium-like protrusions with only
      a minimal set of purified proteins points to an active participation of the
      membrane in organizing actin filaments at the plasma membrane. In this way,
      elastic interactions between the membrane and cytoskeleton can cooperate with
      accessory proteins to drive cellular shape change.

PMID- 19746193
TI  - A Semiparametric Bayesian Model for Repeatedly Repeated Binary Outcomes.
AB  - We discuss the analysis of data from single nucleotide polymorphism (SNP) arrays
      comparing tumor and normal tissues. The data consist of sequences of indicators
      for loss of heterozygosity (LOH) and involve three nested levels of repetition:
      chromosomes for a given patient, regions within chromosomes, and SNPs nested
      within regions. We propose to analyze these data using a semiparametric model for
      multi-level repeated binary data. At the top level of the hierarchy we assume a
      sampling model for the observed binary LOH sequences that arises from a partial
      exchangeability argument. This implies a mixture of Markov chains model. The
      mixture is defined with respect to the Markov transition probabilities. We assume
      a nonparametric prior for the random mixing measure. The resulting model takes
      the form of a semiparametric random effects model with the matrix of transition
      probabilities being the random effects. The model includes appropriate dependence
      assumptions for the two remaining levels of the hierarchy, i.e., for regions
      within chromosomes and for chromosomes within patient. We use the model to
      identify regions of increased LOH in a dataset coming from a study of treatment
      related leukemia in children with an initial cancer diagnostic. The model
      successfully identifies the desired regions and performs well compared to other
      available alternatives.

PMID- 19746194
TI  - The Urine Proteome as a Biomarker of Radiation Injury: Submitted to Proteomics-
      Clinical Applications Special Issue: "Renal and Urinary Proteomics
      (Thongboonkerd)"
AB  - Terrorist attacks or nuclear accidents could expose large numbers of people to
      ionizing radiation, and early biomarkers of radiation injury would be critical
      for triage, treatment and follow-up of such individuals. However, no such
      biomarkers have yet been proven to exist. We tested the potential of high
      throughput proteomics to identify protein biomarkers of radiation injury after
      total body X-ray irradiation in a rat model. Subtle functional changes in the
      kidney are suggested by an increased glomerular permeability for macromolecules
      measured within 24 hours after TBI. Ultrastructural changes in glomerular
      podocytes include partial loss of the interdigitating organization of foot
      processes. Analysis of urine by LC-MS/MS and 2D-GE showed significant changes in
      the urine proteome within 24 hours after TBI. Tissue kallikrein 1-related
      peptidase, cysteine proteinase inhibitor cystatin C and oxidized histidine were
      found to be increased while a number of proteinase inhibitors including
      kallikrein-binding protein and albumin were found to be decreased post
      irradiation. Thus, TBI causes immediately detectable changes in renal structure
      and function and in the urinary protein profile. This suggests that both systemic
      and renal changes are induced by radiation and it may be possible to identify a
      set of biomarkers unique to radiation injury.

PMID- 19746195
TI  - The wake structure and thrust performance of a rigid low-aspect-ratio pitching
      panel.
AB  - Thrust performance and wake structure were investigated for a rigid rectangular
      panel pitching about its leading edge in a free stream. For Re(C) = O(10(4)),
      thrust coefficient was found to depend primarily on Strouhal number St and the
      aspect ratio of the panel AR. Propulsive efficiency was sensitive to aspect ratio
      only for AR less than 0.83; however, the magnitude of the peak efficiency of a
      given panel with variation in Strouhal number varied inversely with the amplitude
      to span ratio A/S, while the Strouhal number of optimum efficiency increased with
      increasing A/S. Peak efficiencies between 9 % and 21 % were measured. Wake
      structures corresponding to a subset of the thrust measurements were investigated
      using dye visualization and digital particle image velocimetry. In general, the
      wakes divided into two oblique jets; however, when operating at or near peak
      efficiency, the near wake in many cases represented a Karman vortex street with
      the signs of the vortices reversed. The three-dimensional structure of the wakes
      was investigated in detail for AR = 0.54, A/S = 0.31 and Re(C) = 640. Three
      distinct wake structures were observed with variation in Strouhal number. For
      approximately 0.20 < St < 0.25, the main constituent of the wake was a horseshoe
      vortex shed by the tips and trailing edge of the panel. Streamwise variation in
      the circulation of the streamwise horseshoe legs was consistent with a spanwise
      shear layer bridging them. For St > 0.25, a reorganization of some of the
      spanwise vorticity yielded a bifurcating wake formed by trains of vortex rings
      connected to the tips of the horseshoes. For St > 0.5, an additional structure
      formed from a perturbation of the streamwise leg which caused a spanwise
      expansion. The wake model paradigm established here is robust with variation in
      Reynolds number and is consistent with structures observed for a wide variety of
      unsteady flows. Movies are available with the online version of the paper.

PMID- 19746196
TI  - Robust Non-inferiority Tests for Potency of a Test Drug Against a Reference Drug:
      (To appear in Statistics in Biopharmaceutical Research ).
AB  - In comparing test formulations of a drug product to reference formulations it is
      necessary to check that the test formulation has as much biologic activity as the
      reference within some indifference zone. A modern method for testing this
      relative potency is to fit a nonlinear model of the dose response curve,
      constrained such that the dose-response of the test is modeled with the same
      function as the reference except for a multiplicative parameter on the dose. This
      method works well as long as the nonlinear model fits the data. Although tests of
      this fit are mentioned in the literature, how relative potency should be measured
      when those tests fail has not been addressed. We study the use of the sandwich
      estimator of variance for this non-inferiority potency problem when the model
      does not fit the data. We focus on the simple linear model. Using the sandwich
      variance, the inferences are asymptotically valid even if the model does not
      hold. We discuss interpretation of the results under the misspecified linear
      model, and show by simulation that the method performs well in some practical
      cases. Finally, we give advice for designing a study that uses these methods.

PMID- 19746197
TI  - Effects of three-dimensionality on thrust production by a pitching panel.
AB  - To understand the fluid dynamics of a biologically inspired unsteady low-aspect
      ratio propulsor, unsteady pressure distributions were measured and compared with
      time-averaged thrust performance and wake visualizations. The experiments were
      performed on rigid rectangular panels with different aspect ratios, pitching in a
      uniform flow. Panel aspect ratio and pitching amplitude were shown to affect the
      magnitude and time dependence of the pressure distribution on the panel surface,
      the vorticity generation on the panel, and thrust production. A new scaling is
      proposed that includes these parameters and collapses the oscillating pressure
      magnitude and the thrust coefficient.

PMID- 19746198
TI  - On the evolution of the wake structure produced by a low-aspect-ratio pitching
      panel.
AB  - Flow visualization is used to interrogate the wake structure produced by a rigid
      flat panel of aspect ratio (span/chord) 0.54 pitching in a free stream at a
      Strouhal number of 0.23. At such a low aspect ratio, the streamwise vorticity
      generated by the plate tends to dominate the formation of the wake. Nevertheless,
      the wake has the appearance of a three-dimensional von Karman vortex street, as
      observed in a wide range of other experiments, and consists of horseshoe vortices
      of alternating sign shed twice per flapping cycle. The legs of each horseshoe
      interact with the two subsequent horseshoes in an opposite-sign, then like-sign
      interaction in which they become entrained. A detailed vortex skeleton model is
      proposed for the wake formation.

PMID- 19746199
TI  - Performance of Information Criteria for Spatial Models.
AB  - Model choice is one of the most crucial aspect in any statistical data analysis.
      It is well known that most models are just an approximation to the true data
      generating process but among such model approximations it is our goal to select
      the "best" one. Researchers typically consider a finite number of plausible
      models in statistical applications and the related statistical inference depends
      on the chosen model. Hence model comparison is required to identify the "best"
      model among several such candidate models. This article considers the problem of
      model selection for spatial data. The issue of model selection for spatial models
      has been addressed in the literature by the use of traditional information
      criteria based methods, even though such criteria have been developed based on
      the assumption of independent observations. We evaluate the performance of some
      of the popular model selection critera via Monte Carlo simulation experiments
      using small to moderate samples. In particular, we compare the performance of
      some of the most popular information criteria such as Akaike Information
      Criterion (AIC), Bayesian Information Criterion (BIC), and Corrected AIC (AICc)
      in selecting the true model. The ability of these criteria to select the correct
      model is evaluated under several scenarios. This comparison is made using various
      spatial covariance models ranging from stationary isotropic to nonstationary
      models.

PMID- 19746201
TI  - Predictors of response to intradetrusor botulinum toxin-A injections in patients
      with idiopathic overactive bladder.
AB  - OBJECTIVES: To evaluate whether there are any demographic or urodynamic
      differences in patients with idiopathic overactive bladder (I-OAB) that respond
      and do not respond to intradetrusor injections of botulinum toxin-A (BTX-A).
      METHODS: This represents a secondary analysis of data collected from an
      investigator initiated randomized trial designed to evaluate clinical differences
      in outcomes for 100 versus 150 U BTX-A in patients with I-OAB. Preinjection
      demographic and urodynamic data were collected. Patients were evaluated 12 weeks
      after injection and were determined to be responders or nonresponders as defined
      by our criteria. Statistical comparisons were made between groups. RESULTS: In
      patients with overactive bladder without incontinence (OAB-Dry), there were no
      variables that could be used to predict response to BTX-A. On univariate
      analysis, younger patients with overactive bladder with incontinence (OAB-Wet)
      were more likely to respond to BTX-A than older patients. However, this
      relationship was no longer statistically significant on multivariate analysis.
      CONCLUSIONS: We were unable to identify any preinjection demographic or
      urodynamic parameters that could aid in predicting which patients will achieve
      clinical response to BTX-A. Future studies are necessary to further evaluate this
      question.

PMID- 19746202
TI  - Radiation recall reaction induced by adjuvant trastuzumab (herceptin).
AB  - Although concerns of radiation sensitization have been raised with concurrent
      trastuzumab (Herceptin) administration, there has been no published case of
      radiation recall reaction associated with trastuzumab. This case describes a
      clinical presentation consistent with a radiation recall reaction following
      administration of adjuvant trastuzumab after neoadjuvant FEC-D chemotherapy and
      locoregional radiotherapy for HER2-positive, locally advanced breast cancer in a
      premenopausal woman. Although the mechanism and etiology of radiation recall
      dermatitis remain unclear, this case raises further hypotheses regarding a
      possible drug dose-dependence and possible predisposing risk factor for the
      development of radiation recall reactions.

PMID- 19746200
TI  - Emerging Roles of Natriuretic Peptides and their Receptors in Pathophysiology of
      Hypertension and Cardiovascular Regulation.
AB  - Thus far, three related natriuretic peptides (NPs) and three distinct receptors
      have been identified, which have advanced our knowledge towards understanding the
      control of high blood pressure, hypertension, and cardiovascular disorders to a
      great extent. Biochemical and molecular studies have been advanced to examine
      receptor function and signaling mechanisms and the role of second messenger cGMP
      in pathophysiology of hypertension, renal hemodynamics, and cardiovascular
      functions. The development of gene-knockout and gene-duplication mouse models
      along with transgenic mice have provided a framework for understanding the
      importance of the antagonistic actions of natriuretic peptides receptor in
      cardiovascular events at the molecular level. Now, NPs are considered as
      circulating markers of congestive heart failure, however, their therapeutic
      potential for the treatment of cardiovascular diseases such as hypertension,
      renal insufficiency, cardiac hypertrophy, congestive heart failure, and stroke
      has just begun to unfold. Indeed, the alternative avenues of investigations in
      this important are need to be undertaken, as we are at the initial stage of the
      molecular therapeutic and pharmacogenomic implications.

PMID- 19746203
TI  - Lymphangitic carcinomatosis as a cause of malignant transient pleural transudate.
AB  - Although it is generally accepted that a malignant transient pleural transudate
      may appear during the early stages of lymphatic obstruction, cases demonstrating
      such probability are rare in literature. A 67-year-old woman was admitted to
      hospital because a lymphangitic carcinomatosis and a transudative infrapulmonary
      pleural effusion with a cytology positive for adenocarcinoma. One month later the
      effusion keeps being positive for adenocarcinoma but exudative in character.
      Lymphatic obstruction appears as the cause of the initial transudative
      characteristics of the pleural effusion.

PMID- 19746204
TI  - Zirconium-catalyzed methylalumination of heterosubstituted arylethynes. Factors
      affecting the regio-, stereo-, and chemoselectivities.
AB  - The Zr-catalyzed methylalumination of heterosubstituted arylethynes containing O,
      S, Cl, and Si can proceed in high yields (>70%) and in a highly regio- and
      stereoselective manner (>=98-99%), although SO(2)Ph, Br, and Cl in a benzylic
      position present serious chemoselectivity-related problems. The low
      regioselectivity of 60% initially observed with o-ethynylphenol (1a) has been
      elevated to >=98% through the use of either a catalytic amount of Zr(ebi)Cl(2) or
      Zr(2-Me-Ind)(2)Cl(2) or, more conveniently, the stoichiometric amount of
      ZrCp(2)Cl(2), ZrCp(2)MeCl, or ZrCp(2)Me(2) in conjunction with the use of a
      deficient amount (0.9 molar equivalent) of I(2) for subsequent iodinolysis.

PMID- 19746205
TI  - How Surface Heterogeneity Affects Protein Adsorption: Annealing of OTS Patterns
      and Albumin Adsorption Kinetics.
AB  - Fluorescence microscopy and intensity histogram analysis techniques were used to
      monitor spatially-resolved albumin adsorption kinetics to model heterogeneous
      surfaces on sub-MUm scales. Several distinct protein subpopulations were
      resolved, each represented by a normal distribution of adsorption densities on
      the adsorbent surface. Histogram analyses provided dynamic information of mean
      adsorption density, spread in adsorption density, and surface area coverage for
      each distinct protein subpopulation. A simple adsorption model is proposed in
      which individual protein binding events are predicted by the summation of
      multiple protein's surface sub-site interactions with different binding energy
      sub-sites on adsorbent surfaces. This model is predictive of the albumin
      adsorption on the patterns produced by one step MU-contact printing (MUCP) of
      octadecyltrichlorosilane (OTS) on glass but fails to describe adsorption once the
      same patterns are altered by a thermal annealing step.

PMID- 19746206
TI  - A nanoporous, transparent microcontainer for encapsulated islet therapy.
AB  - Present-day islet encapsulation techniques such as polymer microcapsules and
      microelectromechanical system (MEMS)-based biocapsules have shown promise in
      insulin replacement therapy, but they each have limitations-the permeability
      characteristics of existing polymeric capsules cannot be strictly controlled
      because of tortuosity and the large size of present-day MEMS biocapsules leads to
      necrotic regions within the encapsulation volume. We report on a new
      microcontainer to encapsulate and immunoprotect islets/beta cells that may be
      used for allo- or xenotransplantation in cell-based therapy. The microcontainers
      have membranes containing nanoslots to permit the bidirectional transport of
      nutrients, secretagogues, and cellular products while immunoprotecting the
      encapsulated cells. The 300-microm microcontainers were fabricated from an epoxy
      based polymer, SU-8, with 50-microm-thick walls. Arrays of 25-nm wide slots were
      created in the SU-8 microcontainer lid. Isolated mouse islets were encapsulated
      in the microcontainer, and their physiological response to glucose was studied
      with fluorescence and two-photon imaging over 48 hours. The physiological
      response of the encapsulated islets was indistinguishable from controls. An
      agarose-filled microcontainer was imaged with magnetic resonance imaging to
      demonstrate the feasibility of future noninvasive, in vivo imaging. The SU-8
      microcontainers maintained mechanical integrity upon islet loading and mechanical
      manipulation. Islet encapsulation, as well as the ability to visualize islet
      function within these transparent microcontainers, was demonstrated.

PMID- 19746207
TI  - Obtaining a foundation for nursing care at the time of patient admission: a
      grounded theory study.
AB  - The nursing process can be viewed as a problem-solving model, but we do not know
      whether use of the whole process including care plans with interventions based on
      nursing diagnoses improves nurses' ability to carry out assessments. Therefore,
      the aim of this study was to illuminate and describe the assessment and decision
      making process performed by nurses who formulated individual care plans including
      nursing diagnosis, goals and interventions or who used standardized care plans
      when a patient was admitted to their ward for care, and those who did not. Data
      collection and analysis were carried out by means of Grounded theory. Nurses were
      observed while assessing patients, after which they were interviewed. The main
      concern of all nurses was to obtain a foundation for nursing care based on four
      strategies; building pre-understanding, creating a caring environment, collecting
      information on symptoms and signs and performing an analysis from different
      perspectives. It appeared that the most important aspect for nurses who did not
      employ care plans was the medical reason for the patient's admission. The nurses
      who employed care plans discussed their decisions in terms of nursing problems,
      needs and risks. The results indicate that nurses who formulated care plans were
      more aware of their professional role.

PMID- 19746208
TI  - National cancer incidence for the year 2002 in Korea.
AB  - PURPOSE: Since the revised Cancer Act of October 2006, cancer registration was
      reactivated, based on the Statistics Law. MATERIALS AND METHODS: The incidence of
      cancer during 2002 was calculated on the basis of the information available from
      the National Cancer Incidence Database. Crude and age-standardized rates were
      calculated by gender for 18 age groups (0 approximately 4, 5 approximately 9, 10
      approximately 14, every five years, 85 years and over). RESULTS: The overall
      crude incidence rates (CRs) were 269.2 and 212.8 per 100,000 for males and
      females, and the overall age-standardized incidence rates (ASRs) were 287.8 and
      172.9 per 100,000, respectively. Among males, the five leading primary cancer
      sites were stomach (CR 62.4, ASR 65.7), lung (CR 45.4, ASR 51.0), liver (CR 43.2,
      ASR 43.7), colon and rectum (CR 30.7, ASR 32.7), and prostate (CR 8.0, ASR 9.6).
      Among females, the most common cancer sites were breast (CR 33.1, ASR 26.9),
      followed by stomach (CR 32.8, ASR 26.0), colon and rectum (CR 23.1, ASR 18.5),
      thyroid (CR 19.1, ASR 15.7), and uterine cervix (CR 18.2, ASR 14.7). In the 0~14
      age group, leukemia was the most common cancer for both genders. For males,
      stomach cancer was the most common cancer in the 15 approximately 64 age-group,
      but lung cancer was more frequent in men 65 or older. For females, thyroid cancer
      among the 15 approximately 34 age-group, breast cancer among 35 approximately 64
      age-group and stomach cancer in women 65 years or older were the most common
      forms of cancer for each age group. The quality indices for the percentage of
      deaths, by death certificate only, were 4.7% for males and 4.5% for females.
      CONCLUSIONS: Since the National Cancer Incidence Database was started, the annual
      percent change of cancer cases increased by 4.8% (4.1% for males, 5.7% for
      females) during 1999 approximately 2002. This value reflects the increase in
      prostate cancer for males and breast and thyroid cancer in females during 2002.
      The timely reporting of improved quality of cancer registration is needed for
      evidence-based decisions regarding cancer control in Korea.

PMID- 19746209
TI  - Caenorhabditis elegans F09E10.3 encodes a putative 3-oxoacyl-thioester reductase
      of mitochondrial type 2 fatty acid synthase FASII that is functional in yeast.
AB  - Caenorhabditis elegans F09E10.3 (dhs-25) was identified as encoding a 3-oxoacyl
      thioester reductase, potentially of the mitochondrial type 2 fatty acid synthase
      (FASII) system. Mitochondrial FASII is a relatively recent discovery in
      metazoans, and the relevance of this process to animal physiology has not been
      elucidated. A good animal model to study the role of FASII is the nematode C.
      elegans. However, the components of nematode mitochondrial FASII have hitherto
      evaded positive identification. The nematode F09E10.3 protein was ectopically
      expressed without an additional mitochondrial targeting sequence in Saccharomyces
      cerevisiae mutant cells lacking the homologous mitochondrial FASII enzyme 3
      oxoacyl-ACP reductase Oar1p. These yeast oar1Delta mutants are unable to respire,
      grow on nonfermentable carbon sources, or synthesize sufficient levels of lipoic
      acid. Mutant yeast cells producing a full-length mitochondrial F09E10.3 protein
      contained NAD(+)-dependent 3-oxoacyl-thioester reductase activity and resembled
      the corresponding mutant overexpressing native Oar1p for the above-mentioned
      phenotype characteristics. This is the first identification of a metazoan 3
      oxoacyl-thioester reductase (see Note Added in Proof).

PMID- 19746210
TI  - An attempt for combining microarray data sets by adjusting gene expressions.
AB  - PURPOSE: The diverse experimental environments in microarray technology, such as
      the different platforms or different RNA sources, can cause biases in the
      analysis of multiple microarrays. These systematic effects present a substantial
      obstacle for the analysis of microarray data, and the resulting information may
      be inconsistent and unreliable. Therefore, we introduced a simple integration
      method for combining microarray data sets that are derived from different
      experimental conditions, and we expected that more reliable information can be
      detected from the combined data set rather than from the separated data sets.
      MATERIALS AND METHODS: This method is based on the distributions of the gene
      expression ratios among the different microarray data sets and it transforms,
      gene by gene, the gene expression ratios into the form of the reference data set.
      The efficiency of the proposed integration method was evaluated using two
      microarray data sets, which were derived from different RNA sources, and a newly
      defined measure, the mixture score. RESULTS: The proposed integration method
      intermixed the two data sets that were obtained from different RNA sources, which
      in turn reduced the experimental bias between the two data sets, and the mixture
      score increased by 24.2%. A data set combined by the proposed method preserved
      the inter-group relationship of the separated data sets. CONCLUSION: The proposed
      method worked well in adjusting systematic biases, including the source effect.
      The ability to use an effectively integrated microarray data set yields more
      reliable results due to the larger sample size and this also decreases the chance
      of false negatives.

PMID- 19746211
TI  - Detection of lung cancer using MAGE A1-6 and SSX4 RT-PCR expression profiles in
      the bronchial wash fluid.
AB  - PURPOSE: Bronchial wash fluid may be a useful for detecting lung cancer. To
      increase the detection rates, we performed molecular analysis with using MAGE A1
      6 and SSX4 RT-PCR on bronchial wash fluid specimens. MATERIALS AND METHODS: We
      obtained 57 lung cancer tissue specimens by bronchoscopic biopsy and 131
      bronchial washes from 96 patients with lung cancer and 35 patients with benign
      lung diseases. The MAGE A1-6 and SSX4 gene expressions were investigated in the
      cancer tissue specimens and bronchial wash fluids. We evaluated the positive
      detection rates of these methods according to the cytology results and the
      clinical findings. RESULTS: For the cancer tissue specimens and the bronchial
      wash fluid, the positive detection rate of MAGE or SSX4 was 91.2% and 75.0%,
      respectively. Combined MAGE and SSX4 PCR and cytology tests showed an 83.3%
      detection rate for the bronchial wash fluid. From bronchial washes of patients
      with benign lung diseases, the positive rates of using MAGE or SSX4 was 11.4%. In
      the bronchial wash fluid of lung cancer patients, 66.7% of the peripheral cancers
      were detected by MAGE or SSX4, while examination with cytology did not detect any
      peripheral lung cancer. CONCLUSION: The application of both MAGE and SSX4 showed
      high sensitivity and specificity for the detection of lung cancer. Thus, MAGE and
      SSX4 RT-PCR may be effectively utilized as additional methods to improve
      detection of lung cancer with using bronchial wash fluids.

PMID- 19746212
TI  - Differences in overall survival when colorectal cancer patients are stratified
      into new TNM staging strategy.
AB  - PURPOSE: The purpose of this study is to determine whether the prognosis can be
      more precisely gauged by the revised 6th AJCC staging system and if this is
      suitable for Korean colorectal cancer patients, and especially for those patients
      in the Youngdong district. MATERIALS AND METHODS: Between September 1996 and
      December 2003, 365 patients with histologically confirmed colorectal cancer were
      analyzed. Kaplan-Meier analyses were used to compare the overall and stage
      specific 5-year survival. All the statistical tests were two-sided. RESULTS: The
      overall 5-year survival for the entire cohort was 62%. According to the stages
      defined by the AJCC fifth edition system, the 5-year stage-specific survival was
      91% for stage I, 82% for stage II, 51% for stage III and 4% for stage IV.
      According to the stages defined by the AJCC sixth edition system, the 5-year
      stage-specific survival was 91% for stage I, 81% for stage IIa, 83% for stage
      IIb, 100% for stage IIIa, 64% for stage IIIb, 37% for stage IIIc and 4% for stage
      IV. The 5-year survival was significantly better for the patients with stage IIIb
      (64%) than those patients with stage IIIc (37%) (p<.001). CONCLUSION: It is
      widely known that the AJCC sixth edition system for colorectal cancer stratifies
      survival more distinctly than does the fifth edition system by providing more
      substages. Our study showed that stage IIIb disease had better survival than
      stage IIIc disease, but we couldn't confirm that this new staging system is
      relevant in our Korean clinical practice due to the small study population.
      Therefore, further study is required in a larger population.

PMID- 19746213
TI  - Phase II study of docetaxel and cisplatin as first-line chemotherapy in patients
      with recurrent or metastatic gastric cancer.
AB  - PURPOSE: Palliative chemotherapy for patients with recurrent or metastatic
      gastric cancer has been shown to have a survival benefit. Docetaxel monotherapy
      has achieved appreciable results for treating gastric cancer. We investigated the
      clinical efficacy and feasibility of a docetaxel and cisplatin combination
      regimen for patients suffering with recurrent or metastatic gastric cancer.
      MATERIALS AND METHODS: Patients with histologically proven, bidimensionally
      measurable lesions of recurrent or metastatic gastric cancer, and they had an
      Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 and no
      prior palliative chemotherapy were eligible for this study. The combination
      chemotherapy regimen consisted of docetaxel 75 mg/m(2) plus cisplatin 75 mg/m(2)
      on day 1, and this was repeated every 3 weeks until disease progression. RESULTS:
      32 patients were enrolled from 2002 to 2005. The objective response rate was
      31.3% (95% confidence interval (CI): 14.2 approximately 48.2%) with no CR. The
      disease control rate was 59.4%. At a median follow up of 38.9 months, the median
      overall survival was 7.4 months (95% CI: 6.3 approximately 8.5). The median time
      to progression was 4.7 months (95% CI: 3.1 approximately 6.3). During a total of
      106 cycles, grade 3 or 4 hematological toxicities were observed as follows:
      neutropenia (39 of 106 cycles) and anemia (3 of 106 cycles). The grade 3 or 4 non
      hematological toxicities included anorexia (18.9%) and nausea/vomiting (21.7%).
      CONCLUSION: Docetaxel and cisplatin combination chemotherapy showed promising
      anti-tumor activity and this was well tolerated as a first-line treatment for
      patients with recurrent or metastatic gastric cancer. Further large, randomized
      phase III studies are warranted.

PMID- 19746214
TI  - Clinical characteristics of primary peritoneal carcinoma.
AB  - PURPOSE: The goal of this study was to determine the clinical and therapeutic
      characteristics of women with a primary peritoneal carcinoma (PPC). MATERIALS AND
      METHODS: A retrospective clinical study was conducted to evaluate 22 women
      diagnosed with a PPC from 1993 to 2007 at the Hospitals of The Catholic
      University of Korea. Diagnoses were based on the Gynecologic Oncology Group
      criteria and clinical data. We collected patient clinicopathological data
      including age, presenting symptoms, pretreatment CA-125 values (U/ml), clinical
      stage (based on the FIGO stage), performance status (using the Eastern
      Cooperative Oncology Group scale), whether cytoreductive surgery was optimal or
      not, types of chemotherapy and response to treatment. We evaluated the clinical
      characteristics and response to treatment, time to treatment failure and overall
      survival. RESULTS: The median overall survival of all patients was 23.1 months.
      The estimated 3-year survival rate was 29% (SE, 13%). The response rate to first
      line platinum-based chemotherapy was 79% and the median time to treatment failure
      was 9.9 months (95% confidence interval, 1.38~18.4 months). By univariate and
      multivariate analysis, performance status was the only significant factor
      associated with overall survival (p<0.05). CONCLUSION: We evaluated the clinical
      characteristics and treatment response of patients with a primary peritoneal
      carcinoma. Our results showed that it is possible to achieve long-term survival
      in patients with PPC. A further clinical study is to need to establish clinical
      characteristics and treatment outcomes.

PMID- 19746215
TI  - Autologous stem cell transplantation using a modified TAM conditioning regimen
      for clinically aggressive non-Hodgkin's lymphoma.
AB  - PURPOSE: High-dose chemotherapy (HDT) and autologous stem cell transplantation
      (ASCT) have been used for the treatment of clinically aggressive non-Hodgkin's
      lymphoma (NHL). However, the superiority of specific conditioning regimens has
      not yet been established. The present study evaluated the efficacy and toxicity
      of a conditioning regimen involving fractionated total body irradiation (TBI),
      and the use of Ara-C and melphalan (TAM) for clinically aggressive NHL. MATERIALS
      AND METHODS: Between March 2002 and December 2004, 31 patients with aggressive
      NHL received fractionated TBI with a dose of 12 Gy over 3 days, and were
      administered 9 g/m(2) Ara-C and 100 mg/m(2) melphalan followed by autologous
      peripheral blood stem Cell Transplantation at the Catholic Hematopoietic Stem
      cell transplantation Center Korea. Patients that responded to first line
      chemotherapy and achieved complete remission (CR), or were in a first sensitive
      relapse were defined as having less advanced disease, while the other patients
      were defined as having more advanced disease. RESULTS: Objective responses were
      obtained in 24 of 31 patients (77.4%), comprising complete remission in 19
      patients (61.3%) and partial remission in 5 (16.1%) patients. The median follow
      up time was 28 months (range 1 approximately 62 months). At 3 years, the overall
      survival and event-free survival (EFS) rates were 62.3% and 47.3%, respectively.
      Patients with less advanced disease and more advanced disease showed 3-year EFS
      rates of 73.3% and 22.5 %, respectively (p=0.006). Early (within the first 100
      days) treatment-related mortality occurred in 3 (9.7%) patients. Of the 31 total
      patients, 15 (48.4%) developed grade 3 mucositis, 22 (70.9%) developed
      neutropenic fever, and two (6.5%) developed interstitial pneumonia syndrome>grade
      3. CONCLUSION: The modified TAM conditioning regimen and ASCT appear to be a
      feasible treatment regimen for clinically aggressive NHL, particularly for
      patients with less advanced disease.

PMID- 19746216
TI  - The chemopreventive effect of retinoids on cellular NF-kappaB activity induced by
      NMU and NEU in human malignant keratinocytes.
AB  - PURPOSE: Retinoids have been shown to be effective in suppressing tumor
      development when chemical carcinogens such as N-nitroso-N-methylurea (NMU) and N
      nitroso-N-ethylurea (NEU) were used to induce mammary tumors in a variety of
      animal models. However, the molecular mechanisms associated with the retinoid
      mediated chemopreventive process, as linked to transcription factor NF-kappaB
      activation, for chemoprevention have not been elucidated. The purpose of this
      study was to determine the implications of NF-kappaB activation on the
      chemopreventive role of retinoids and their effect on cellular NF-kappaB activity
      that's induced by known alkylating chemical carcinogens such as NMU and NEU in
      human transfectant squamous cell carcinoma (SCC-13) cells. MATERIALS AND METHODS:
      The activity of NF-kappaB, as regulated by chemical carcinogens and retinoids,
      was determined in cultured human SCC-13 keratinocytes that were transfected with
      the pNF-kappaB-SEAP-NPT plasmid; this permitted the expression of the secretory
      alkaline phosphatase (SEAP) reporter gene in response to the NF-kappaB activity,
      and the plasmid contained the neomycin phosphotransferase (NPT) gene, which
      confers resistance to geneticin. The reporter enzyme activity was measured using
      a fluorescence detection assay method. RESULTS: All-trans retinoic acid and 13
      cis retinoic acid induced a reduction of NF-kappaB activity up to 64% and 65%,
      respectively, compared to the control. For the treatment of the human
      transfectant cells with chemical carcinogens, all-trans retinoic acid (5 mM) and
      13-cis retinoic acid (5 mM) downregulated the cellular NF-kappaB activation up to
      83% and 85% compared to the NF-kappaB activity that was upregulated by NMU
      (5microM) and NEU (5microM), respectively. CONCLUSION: These results suggest that
      the chemopreventive effect of retinoids may be mediated by the downregulated
      activation of NF-kappaB and that retinoids are implicated in the activation of NF
      kappaB in human skin cells.

PMID- 19746217
TI  - A case of organizing pneumonia associated with rituximab.
AB  - Rituximab is a human/murine chimeric anti-CD20 monoclonal antibody used to treat
      CD20-positive B-cell non-Hodgkin's lymphoma (NHL). Although most of the adverse
      effects associated with rituximab are usually reversible and temporary infusion
      related reactions, including fever, chills, flushing and skin reactions, there
      are several reports of pulmonary events after long-term administration of
      rituximab. We present a case of asymptomatic nodular organizing pneumonia
      occurring during rituximab-based chemotherapy in a patient with non-Hodgkin's
      lymphoma.

PMID- 19746218
TI  - Bone metastasis from primary hepatocellular carcinoma: characteristics of soft
      tissue formation.
AB  - PURPOSE: To assess the characteristics of bone metastasis from hepatocellular
      carcinoma and the radiation field arrangement based on imaging studies. MATERIALS
      AND METHODS: Fifty-three patients (84 lesions) with bone metastasis from a
      primary hepatocellular carcinoma completed palliative radiation therapy. All
      patients underwent one of following imaging studies prior to the initiation of
      radiation therapy: a bone scan, computed tomography or magnetic resonance
      imaging. The median radiation dose was 30 Gy (7 approximately 40 Gy). We
      evaluated retrospectively the presence of soft tissue formation and the
      adjustment of the radiation field based on the imaging studies. RESULTS: Soft
      tissue formation at the site of bony disease was identified from either a CT/MRI
      scan (41 lesions) or from a symptomatic palpable mass (5 lesions). The adjustment
      of the radiation field size based on a bone scan was necessary for 31 of 41 soft
      tissue forming lesions (75.6%), after a review of the CT/MRI scan. The median
      survival from the initial indication of a hepatoma diagnosis was 8 months (2 to
      71 months), with a 2-year survival rate of 38.6%. The median survival from the
      detection of a bone metastasis was 5 months (1 to 38 months) and the 1-year
      overall survival rate was 8.7%. CONCLUSION: It was again identified that bone
      metastasis from a primary hepatocellular carcinoma is accompanied by soft tissue
      formation. From this finding, an adjustment of the radiation field size based on
      imaging studies is required. It is advisable to obtain a CT or MRI scan of
      suspected bone metastasis for better tumor volume coverage prior to the
      initiation of radiation therapy.

PMID- 19746219
TI  - Activation of ATM-dependent DNA damage signal pathway by a histone deacetylase
      inhibitor, trichostatin A.
AB  - PURPOSE: Ataxia-telangiectasia mutated (ATM) kinase regulates diverse cellular
      DNA damage responses, including genome surveillance, cell growth, and gene
      expression. While the role of histone acetylation/deacetylation in gene
      expression is well established, little is known as to whether this modification
      can activate an ATM-dependent signal pathway, and whether this modification can
      thereby be implicated in an ATM-mediated DNA damage response. MATERIALS AND
      METHODS: Formation of H2AXgamma foci was examined in HeLa and U(2)OS cells
      following treatment with a histone deacetylase inhibitor, Trichostatin A (TSA).
      We determine an ATM-dependency of the TSA-induced DNA damage signal pathway using
      isogenic A-T (ATM(-)) and control (ATM(+)) cells. We monitored the
      phosphorylation of ATM, an ATM-downstream effector kinase, Chk2, and H2AXgamma to
      detect the activation of the ATM-dependent DNA damage signal pathway. RESULTS:
      Exposure of cells to TSA results in the formation of H2AXgamma foci in HeLa and
      U(2)OS cells. The TSA-induced formation of H2AXgamma foci occurs in an ATM
      dependent manner. TSA induces phosphorylation of serine 1981 of ATM, accumulation
      of phosphorylated H2AX and Chk2, and formation of H2AX foci, in a manner
      analogous to genotoxic DNA damage. CONCLUSION: In this work, we show that TSA
      induces a DNA damage signaling pathway in an ATM-dependent manner. These results
      suggest that ATM can respond to altered histone acetylation induced by the
      histone deacetylase inhibitor, TSA.

PMID- 19746220
TI  - Glucose transporter-1 expression in squamous cell carcinoma of the tongue.
AB  - PURPOSE: Tumor cells are known to express hypoxia-related proteins such as
      glucose transporter-1 (Glut-1). These hypoxia-induced changes may allow tumor
      cells to survive under sustained hypoxic microenvironments, and the surviving
      tumor cell under hypoxia may develop a more aggressive phenotype and so result in
      a poor prognosis. MATERIALS AND METHODS: The Glut-1 expression was analyzed by
      immunohistochemistry, and its association with the prognosis was assessed in 60
      patients with squamous cell carcinoma of the tongue. RESULTS: The Glut-1
      expression was diffuse with a membranous pattern, and the median percentage of
      Glut-1 positive tumor cells was 60% (range: 0.0 approximately 90.0%). A high Glut
      1 expression (the percentage of positive tumor cells >or= the median value, 60%)
      was associated with the location of primary lesion, lymph node metastasis status
      and disease stage (p<0.05). The expression of Glut-1 was correlated with the Ki
      67 expression (r=0.406, p=0.001). Microvessel density, as represented by CD31
      staining, was also correlated with the Glut-1 expression although its
      significance is weak (r=0.267, p=0.039). On the univariate analysis, the group
      with a high Glut-1 expression showed poorer overall survival than the group with
      a low Glut-1 expression (p<0.05). However, the Glut-1 expression failed to show
      any independent prognostic significance on the multivariate analysis. CONCLUSION:
      The expression of Glut-1 may be useful for predicting the prognosis and
      determining the treatment strategy for the management of squamous cell carcinoma
      of the tongue.

PMID- 19746221
TI  - A locally advanced breast cancer with difficult differential diagnosis of
      carcinosarcoma and atypical medullary carcinoma, which had poor response to
      adriamycin- and taxane-based neoadjuvant chemotherapy: a case report.
AB  - Atypical medullary carcinomas and carcinosarcoma have unique histopathological
      features. Here we present a case with a breast malignancy that had pathological
      characteristics of both. A 54-year old patient with a malignant breast mass
      received 6 cycles of adriamycin-based chemotherapy, followed by 3 cycles of
      paclitaxel monotherapy, and had a poor clinical response to treatment. A modified
      radical mastectomy was performed. The pathological diagnosis was complicated by
      an inability to distinguish between atypical medullary carcinoma and
      carcinosarcoma. The findings included a tumor that was well-circumscribed, high
      grade and a syncytial growth pattern as well as biphasic sarcomatous and
      carcinomatous characteristics. In conclusion, atypical medullary carcinoma and
      carcinosarcoma of the breast have entirely different prognoses and should be
      managed differently. Both should be treated by surgical resection, and additional
      therapy should be considered based on the cancer with the poorer prognosis.

PMID- 19746222
TI  - The efficacy of an induction chemotherapy combination with docetaxel, cisplatin,
      and 5-FU followed by concurrent chemoradiotherapy in advanced head and neck
      cancer.
AB  - PURPOSE: This study was performed to determine the feasibility and safety of the
      use of induction chemotherapy combined with docetaxel, cisplatin, and 5
      fluorouracil (TPF) followed by concurrent chemoradiation therapy for locally
      advanced squamous cell carcinoma of the head and neck (SCCHN). MATERIALS AND
      METHODS: The patients, that were initially not treated for locally advanced
      SCCHN, underwent three cycles of induction chemotherapy every 3 weeks at a dose
      of 70 mg/m(2) docetaxel D1, 75 mg/m(2) cisplatin D1, 1000 mg/m(2) 5-FU D1-4, and
      subsequently received concurrent chemoradiation therapy. RESULTS: Forty-nine
      patients were enrolled in this study and forty-three of the patients completed
      the treatment. The median duration of follow-up was 18 months (range, 6
      approximately 39 months). All of the patients had stage III (26.5%) or IV (73.5%)
      squamous cell carcinoma. After sequential therapy, a complete response and
      partial response was seen in 28 (65.2%) and 13 (30.2%) patients, respectively.
      The overall response rate was 95.4%. Overall survival and progression-free
      survival (PFS) at 2 years were 88.7% and 69.7%, respectively. Grade 3
      approximately 4 neutropenia occurred in 42.2% of the patients and grade 4
      thrombocytopenia in 1 cycle (0.7%). Two patients (4.1%) died during the induction
      chemotherapy due to pneumonia and a subdural hemorrhage, respectively. The group
      of patients over 65 years of age showed a significant lower dose intensity than
      that of patients under 65 years of age, but PFS was not significantly different
      between two groups (p=0.105). CONCLUSION: TPF induction chemotherapy followed by
      concurrent chemoradiotherapy showed a high level of CR and moderate treatment
      induced toxicity. Adequate dose modification in elderly patients should be
      considered to maintain efficacy and avoid treatment-related toxicity.

PMID- 19746223
TI  - Extraskeletal mesenchymal chondrosarcoma of the heart responded to systemic
      chemotherapy: a case report.
AB  - Mesenchymal chondrosarcoma is a rare cartilaginous neoplasm of an extraskeletal
      origin, and this predominately occurs in the head and neck, and also in the lower
      extremities. Fewer than twenty cases of cardiac mesenchymal chondrosarcoma have
      so far been reported on. For the most part, the results of treatment for patients
      with this condition have been dismal. In this study, we describe a case of
      cardiac mesenchymal chondrosarcoma that responded to chemotherapy following
      surgical biopsy. A 46-year-old man was referred for evaluation of his pleural
      effusions in both lungs. Chest computed tomography revealed an ovoid-shaped mass
      in the posterior wall of the patient's left atrium. The echocardiogram revealed a
      large ovoid-shaped immobile mass (11x6 cm(2)) in the pericardiac space, which was
      attached to the posterior wall of the left atrium. Emergency pericardiostomy with
      closure thoracostomy was performed. Seven days later, a thoracotomy was performed
      for reduction and diagnosis of the cardiac mass. The pathological diagnosis was
      extraskeletal mesenchymal chondrosarcoma of the heart.. Postoperative
      chemotherapy was performed for the huge remaining mass with a combined regimen of
      etoposide, ifosfamide and cisplatin. After 6 cycles, the patient showed a partial
      response without symptoms. Although cardiac mesenchymal chondrosarcoma has been
      reported to be chemotherapy-resistant with a short survival duration,
      chemotherapy may prove to be an effective treatment modality.

PMID- 19746224
TI  - Oxaliplatin, 5-FU, folinic acid as first-line palliative chemotherapy in elderly
      patients with metastatic or recurrent gastric cancer.
AB  - PURPOSE: We investigated the efficacy and safety of a combination of oxaliplatin,
      5-fluorouracil (5-FU), and folinic acid (FA) as first-line palliative
      chemotherapy for elderly patients with metastatic or recurrent gastric cancer.
      MATERIALS AND METHODS: The study patients were chemotherapy-naive patients (> 65
      years old) with histologically confirmed, metastatic or recurrent gastric cancer.
      Chemotherapy consisted of oxaliplatin 100 mg/m(2) and FA 100 mg/m(2) (2-hour
      infusion), and then 5-FU 2400 mg/m(2) (46-hour continuous infusion) every 2
      weeks. RESULTS: A total of 37 patients were studied between April 2004 and
      October 2006. Of the 34 evaluable patients, none achieved a complete response
      (CR) and 14 achieved a partial response (PR), resulting in an overall response
      rate of 41.2%. The median time to progression (TTP) was 5.7 months (95% CI:
      4.2~6.3 months) and the median overall survival (OS) was 9.8 months (95% CI:
      4.4~12.0 months). The main hematologic toxicities were anemia and neutropenia,
      which were observed in 56.7% and 32.4% of the patients, respectively. Grade 3/4
      neutropenia was observed in 8.1% of the patients. None of the patients
      experienced febrile neutropenia. Peripheral neuropathy occurred in 35.1% of the
      patients and all were grade 1/2. CONCLUSION: This oxaliplatin/5-FU/FA regimen
      showed good efficacy and an acceptable toxicity profile in elderly patients with
      metastatic or recurrent gastric cancer.

PMID- 19746225
TI  - Functional link between DNA damage responses and transcriptional regulation by
      ATM in response to a histone deacetylase inhibitor TSA.
AB  - PURPOSE: Mutations in the ATM (ataxia-telangiectasia mutated) gene, which encodes
      a 370 kd protein with a kinase catalytic domain, predisposes people to cancers,
      and these mutations are also linked to ataxia-telangiectasia (A-T). The histone
      acetylaion/deacetylation- dependent chromatin remodeling can activate the ATM
      kinase-mediated DNA damage signal pathway (in an accompanying work, Lee, 2007).
      This has led us to study whether this modification can impinge on the ATM
      mediated DNA damage response via transcriptional modulation in order to
      understand the function of ATM in the regulation of gene transcription. MATERIALS
      AND METHODS: To identify the genes whose expression is regulated by ATM in
      response to histone deaceylase (HDAC) inhibition, we performed an analysis of
      oligonucleotide microarrays with using the appropriate cell lines, isogenic A-T
      (ATM(-)) and control (ATM(+)) cells, following treatment with a HDAC inhibitor
      TSA. RESULTS: Treatment with TSA reprograms the differential gene expression
      profile in response to HDAC inhibition in ATM(-) cells and ATM(+) cells. We
      analyzed the genes that are regulated by TSA in the ATM-dependent manner, and we
      classified these genes into different functional categories, including those
      involved in cell cycle/DNA replication, DNA repair, apoptosis,
      growth/differentiation, cell- cell adhesion, signal transduction, metabolism and
      transcription. CONCLUSIONS: We found that while some genes are regulated by TSA
      without regard to ATM, the patterns of gene regulation are differentially
      regulated in an ATM-dependent manner. Taken together, these finding indicate that
      ATM can regulate the transcription of genes that play critical roles in the
      molecular response to DNA damage, and this response is modulated through an
      altered HDAC inhibition-mediated gene expression.

PMID- 19746226
TI  - Enhancement of plasmacytoma cell growth by ascorbic acid is mediated via glucose
      6-phosphate dehydrogenase.
AB  - PURPOSE: We investigated the mechanism by which some types of cancer cells grow
      faster in the presence of ascorbic acid supplementation. MATERIALS AND METHODS:
      Adj.PC-5, a mouse plasmacytoma cell, is known to show ascorbic acid-dependent
      growth and was chosen as a test system. The growth of cancer cells was measured
      by the colony number on soft agar or the cellular proliferation in suspension
      culture. The ascorbate level was measured by a high performance liquid
      chromatography system with an electrochemical detector. Glucose 6-phosphate
      dehydrogenase was analyzed both on the specific enzyme activity level and on the
      transcription level by performing Northern blot analysis. RESULTS: Ascorbyl 2
      phosphate among the ascorbate derivatives was the most efficient in stimulating
      cell growth. The intracellular and extracellular ascorbate concentrations
      following treatment with either ascorbate or ascorbyl 2-phosphate suggest that
      the superiority of ascorbyl 2-phosphate for stimulating cell growth may be due to
      its slow conversion to ascorbate in the culture medium. The steady transformation
      to ascorbate ensures sustained levels of ascorbate in the culture medium and
      thereby maximizes the growth stimulatory effect of ascorbate. Ascorbyl 2
      phosphate markedly enhanced, in a concentration-and time-dependent manner, mRNA
      synthesis as well as the enzymatic activity of glucose 6-phosphate dehydrogenase,
      which is known to be a rate-limiting enzyme in cell growth. On the other hand,
      simultaneous addition of dehydroisoandrosterone, a well- known inhibitor of
      glucose 6-phosphate dehydrogenase, to the culture medium abrogated the growth
      stimulation by ascorbyl 2-phosphate, and it also reduced the glucose 6-phosphate
      dehydrogenase activity proportionately. CONCLUSIONS: The results from this study
      suggest that enhanced glucose 6-phosphate dehydrogenase activity may at least in
      part explain the stimulation of cell growth by ascorbate or ascorbyl 2-phosphate.

PMID- 19746227
TI  - Laparoscopic assisted distal rectal cancer resection with preoperative concurrent
      chemoradiotherapy.
AB  - PURPOSE: Anatomy of deep pelvis, narrow distal margin and tumor invasion into
      neighbor organ are obstacles for curative radical resection for advanced cancer
      of distal rectum. Technically, laparoscopic application after downstaging the
      tumor with preoperative concurrent chemotherapy (CCRT) may give a solution to
      overcome the anatomical difficulties. We compared the results of laparoscopic
      surgery in the patients who received CCRT with those of patients who had
      conventional surgery. MATERIALS AND METHODS: A continuous infusion of 5FU plus
      leucovorin and radiotherapy (50.4 Gy) in 28 fractions was given each patient as
      CCRT. They underwent D2 radical resection with TME and ANP for the rectal cancer
      in 4 weeks. RESULTS: Thirty three patients had laparoscopic resection such as
      LAR, colo-anal anastomosis and APR. The results were compared with 12 cases of
      the conventional resections. As a result of preoperative CCRT, the cancer was
      down-staged in 71%. Two year disease free survival was 75% and 74% in the group
      of conventional and laparoscopic resection, respectively (p=0.427). Ileus,
      voiding difficulty and leakage after surgery were not different between two
      groups. Weakness of ejaculation was noted in 9 approximately 11% of both groups.
      The DFS of the preoperative CCRT followed by radical resection in the groups with
      a response was more favorable than that in the group with progressive or stable
      disease. CONCLUSION: Radical resection of advanced distal rectal cancer could be
      done with performing a laparoscopic assisted operation after CCRT induced down
      staging. We may suggest that laparoscopic assisted resection is a good treatment
      option as it doesn't increase the complications and it has a compatible survival
      rate to conventional surgery.

PMID- 19746228
TI  - Orbital infiltration as the first site of relapse of primary testicular T-cell
      lymphoma.
AB  - A 43-year-old male presented with a painless left testicular mass. The pathologic
      diagnosis of the radical orchiectomy specimen was peripheral T-cell lymphoma,
      unspecified (PTCL-u). According to the Ann Arbor staging system, his initial
      stage was III because of the right nasopharyngeal involvement. After first-line
      chemotherapy with four courses of the CHOP regimen and this was followed by
      involved-field radiotherapy, he achieved complete remission. Two months later,
      disease recurred to the left ciliary body of the left eye without evidence of
      involvement at other sites. Although the patient received intensive chemotherapy
      with autologous hematopoietic stem cell transplantation, he ultimately died of
      leptomeningeal seeding. Because both the central nervous system (CNS) and the
      orbit are sanctuary sites for chemotherapy, orbital infiltration of lymphoma
      should prompt physicians to evaluate involvement of the CNS and to consider
      performing prophylactic intrathecal chemotherapy as a treatment option.

PMID- 19746229
TI  - Retraction: tetraarsenic oxide-mediated apoptosis in a cervical cancer cell line,
      SiHa.

PMID- 19746230
TI  - Analysis of cellular changes resulting from forced expression of Dickkopf-1 in
      hepatocellular carcinoma cells.
AB  - PURPOSE: Recent studies have shown that Dickkopf-1 (DKK-1) is overexpressed in
      some tumors, including hepatocellular carcinoma. However, the role of increased
      DKK-1 in these tumors is not known. In this study, the DKK-1 expression in
      hepatocellular carcinoma (HCC) cell lines was evaluated and the effect of DKK-1
      overexpression in HCC cell lines was studied. MATERIALS AND METHODS: The
      expression of DKK-1 in hepatocellular carcinoma cell lines was evaluated by RT
      PCR. Stable cell lines that overexpressed DKK-1 were established. Cell growth,
      adhesion, migration and invasion assays were performed. RESULTS: RT-PCR analysis
      showed that 5 out of 8 HCC cell lines expressed DKK-1. The forced expression of
      DKK-1 suppressed the growth of cells and increased the population of cells in the
      sub-G1 phase. In addition, DKK-1 reduced the cellular adhesion capacity to
      collagen type I and fibronectin, and it increased migratory capacity. However,
      overexpression of DKK-1 did not increase the invasion capacity of the HCC cell
      line. CONCLUSION: Collectively, our data suggest that overexpression of DKK-1
      affects the biology of HCC cells.

PMID- 19746231
TI  - Radiation-induced necrosis deteriorating neurological symptoms and mimicking
      progression of brain metastasis after stereotactic-guided radiotherapy.
AB  - PURPOSE: Although radiation-induced necrosis (RIN) is not a tumor in itself, the
      lesion progressively enlarges with mass effects and diffuse peritumoral edema in
      a way that resembles neoplasm. To identify the RIN that mimics progression of
      brain metastasis, we performed surgical resections of symptomatic RIN lesions.
      MATERIALS AND METHODS: From June 2003 to December 2005, 7 patients received
      stereotactic-guided radiotherapy (SRT) for metastatic brain tumor, and they later
      underwent craniotomy and tumor resection due to the progressive mass effects and
      the peritumoral edema that caused focal neurological deficit. On MR imaging, a
      ring-like enhanced single lesion with massive peritumoral edema could not be
      distinguished from progression of brain metastasis. RESULTS: Four patients had
      non-small cell lung cancer, 2 patients had colorectal cancer and 1 patient had
      renal cell carcinoma. The mean tumor volume was 8.7 ml (range: 3.0 approximately
      20.7 ml). The prescribed dose of SRT was 30 Gy with 4 fractions for one patient,
      18 Gy for two patients and 20 Gy for the other four patients. The four patients
      who received SRT with a dose of 20 Gy had RIN with or without microscopic
      residual tumor cells. CONCLUSIONS: Early detection of recurrent disease after
      radiotherapy and identifying radiation-induced tissue damage are important for
      delivering adequate treatment. Therefore, specific diagnostic tools that can
      distinguish RIN from progression of metastatic brain tumor need to be developed.

PMID- 19746232
TI  - Retraction: comparison of As2O3 and As4O6 in the detection of SiHa cervical
      cancer cell growth inhibition pathway.

PMID- 19746233
TI  - A phase II study of paclitaxel and cisplatin as salvage therapy for patients with
      advanced or metastatic gastric cancer.
AB  - PURPOSE: To evaluate the therapeutic activity and safety of paclitaxel and
      cisplatin combination chemotherapy in patients with advanced or metastatic
      gastric cancers that are unresponsive to primary chemotherapy. MATERIALS AND
      METHODS: Advanced or metastatic gastric cancer patients unresponsive to first
      line chemotherapy were entered into this trial. The treatment regimen consisted
      of paclitaxel, 175 mg/m(2) by 3-hour infusion on day 1, and cisplatin, 60 mg/m(2)
      by 1 hour infusion on day 1, with the treatment repeated every 3 weeks. RESULTS:
      37 patients were entered in this study, with 32 fully evaluable for response. 4
      (13%), 13 (40%) and 15 (47%) patients achieved a partial response, stable disease
      and progressed, respectively. The median time to progression was 4.0 months (95%
      CI: 2.0 approximately 6.0 months), and the median overall survival was 12.6
      months (95% CI: 5.5 approximately 19.7 months), with a 1-year survival rate of
      54%. Of a total of 135 cycles of chemotherapy, grades 3 and 4 hematological
      toxicities were neutropenia (14%) and anemia (3%). Grade >or=2 neuropathy was
      observed in 6 patients (17%). CONCLUSION: The combination of paclitaxel and
      cisplatin is an effective and tolerable salvage treatment modality for advanced
      gastric cancer.

PMID- 19746234
TI  - Induction chemotherapy of docetaxel and Cisplatin for the elderly patients with
      squamous cell carcinoma of the head and neck.
AB  - PURPOSE: Although concurrent chemoradiotherapy (CCRT) has been considered as a
      standard treatment for locally advanced squamous cell carcinoma of the head and
      neck (SCCHN), this treatment is associated with increased toxicities such as
      mucositis and dermatitis. As a result, the dose intensity can be reduced and
      interruptions of radiotherapy are more common for CCRT than for sequential
      treatment, especially for the elderly patients. This prospective study was
      performed to assess the efficacy and safety profiles of the induction
      chemotherapy of docetaxel and cisplatin for elderly patients with locally
      advanced SCCHN. MATERIALS AND METHODS: Patients over 65 years of age with locally
      advanced SCCHN were treated with docetaxel (70 mg/m(2)) and cisplatin (75
      mg/m(2)) every 21 days. The chemotherapy consisted of two cycles with a third
      cycle that was administered to the responding patients. Patients who did not
      respond to initial chemotherapy underwent radiotherapy as a definitive local
      treatment. RESULTS: Fifty patients were enrolled in this study and 44 patients
      were assessable for response and toxicity. The overall response rate was 88%, 16
      patients (36%) achieved a complete response and 23 patients (52%) achieved a
      partial response. After a median follow-up of 24 months (range: 9 approximately
      38 months) the median disease free period and overall survival period had not yet
      been reached. The one year and two year survival rates were 89% and 70%,
      respectively. The most common grade 3/4 adverse event was neutropenia, which
      occurred in 33 patients (75%) and 4 patients had febrile neutropenia. CONCLUSION:
      Combination chemotherapy of docetaxel and cisplatin is an effective regimen with
      an acceptable safety profile as the induction treatment for elderly patients
      suffering with SCCHN.

PMID- 19746235
TI  - Sequential responses of adenocarcinoma of the lung to erlotinib after gefitinib
      in never smoker Korean woman.
AB  - A patient with adenocarcinoma of the lung was treated sequentially using two
      kinds of EGFR tyrosine kinase inhibitors, gefitinib and erlotinib. The patient
      was a 73-year-old female who received gefitinib as a second line treatment, which
      resulted in a partial response with response duration of 6 months. After
      progression of the disease, the patient received erlotinib, which resulted in
      partial response again with response duration of 11.5 months. This observation
      suggests that treatment with erlotinib may be effective in patients who develop
      progressive disease after a primary treatment with gefitinib following an initial
      response.

PMID- 19746237
TI  - Improving conventional or low dose metronomic chemotherapy with targeted
      antiangiogenic drugs.
AB  - One of the most significant developments in medical oncology practice has been
      the approval of various antiangiogenic drugs for the treatment of a number of
      different malignancies. These drugs include bevacizumab (Avastin), the anti-VEGF
      monoclonal antibody. Thus far, bevacizumab appears to induce clinical benefit in
      patients who have advanced metastatic disease only or primarily when it is
      combined with conventional chemotherapy. The reasons for the chemo-enhancing
      effects of bevacizumab are unknown, and this is a subject that we have been
      actively studying along with additional ways that antiangiogenic drugs may be
      combined with chemotherapy. In this respect, we have focused much of our effort
      on metronomic low dose chemotherapy. We have been studying the hypothesis that
      some chemotherapy drugs at maximum tolerated doses or other cytotoxic- like drugs
      such as acute "vascular disrupting agents" (VDAs) can cause an acute mobilization
      of proangiogenic cells from the bone marrow which home to and colonize the
      treated tumors, thus accelerating their recovery. These cells include endothelial
      progenitor cells. This systemic process can be largely blocked by a targeted
      antiangiogenic drug, e.g. anti-VEGFR-2 antibodies. In addition, metronomic
      chemotherapy, i.e., close regular administration of chemotherapy drugs at low non
      toxic doses with no breaks, over prolonged periods of time not only prevents the
      acute CEP bone marrow response, but can even target the cells. This potential
      antiangiogenic effect of metronomic chemotherapy can also be boosted by
      combination with a targeted antiangiogenic agent. Treatment combinations of
      metronomic chemotherapy and an antiangiogenic drug have moved into phase II
      clinical trial testing with particularly encouraging results thus far reported in
      metastatic breast and recurrent ovarian cancer. Oral chemotherapy drugs such as
      cyclophosphamide (CTX), methotrexate are the main chemotherapeutics used for such
      trials. Oral 5-FU prodrugs such as UFT would also appear to be highly suitable
      based on long term adjuvant therapy studies in patients. Recent preclinical
      results using metronomic cyclophosphamide and metronomic UFT in models of
      advanced metastatic breast cancer suggest that this type of combination might be
      particularly promising for metronomic chemotherapy in this indication,
      particularly when combined with a targeted antiangiogenic drug.

PMID- 19746238
TI  - The survival of osteosarcoma patients 10 years old or younger is not worse than
      the survival of older patients: a retrospective analysis.
AB  - PURPOSE: This study aimed to assess whether a young age at the time of diagnosis
      with osteosarcoma has value to predict the prognosis. MATERIALS AND METHODS:
      Sixty-seven children with stage II osteosarcoma were stratified according to the
      age of 10. There were 32 preadolescents (<or=10 years) and 35 adolescents
      (10<age<or=15 years). The patients were analyzed for their clinical
      characteristics, the histologic response to preoperative chemotherapy, event-free
      survival (EFS) and the patterns of relapse. RESULTS: After a median follow-up of
      54 months (range: 6 approximately 153 months), the 5-year EFS of the
      preadolescent and adolescent groups was 64.5+/-9.3% and 58.2+/-9.1%,
      respectively, and age did not have any statistical significance for survival
      (p=0.55). Cox regression analysis revealed that both the serum level of alkaline
      phosphatase and the histologic response to preoperative chemotherapy were
      significantly related to survival of the 67 patients. Those patients aged less
      than 7 years responded poorly to preoperative chemotherapy and their rate of
      amputation was 43%. However, their 5-year EFS was not statistically different
      from the older patients (57.1+/-18.7 vs 67.7+/-6.3%, respectively, p=0.58).
      CONCLUSIONS: We could not find any statistical difference in the clinical
      characteristics and survival from osteosarcoma for the preadolescents and
      adolescents, so the current approach of having the same protocol for both groups
      of patients seems to be reasonable.

PMID- 19746240
TI  - A multicentre, randomized, double-blind placebo-controlled trial evaluating
      rosiglitazone for the prevention of atherosclerosis progression after coronary
      artery bypass graft surgery in patients with type 2 diabetes. Design and
      rationale of the VeIn-Coronary aTherOsclerosis and Rosiglitazone after bypass
      surgerY (VICTORY) trial.
AB  - BACKGROUND: The number of patients with coronary artery disease and type 2
      diabetes will increase dramatically over the next decade. Diabetes has been
      related to accelerated atherosclerosis and many patients with diabetes will
      require coronary artery bypass graft (CABG) surgery utilizing saphenous vein
      grafts. After CABG, accelerated atherosclerosis in saphenous vein grafts leads to
      graft failure in approximately 50% of cases over a 10-year period. Rosiglitazone,
      a peroxisome proliferator-activated receptor-gamma agonist, has been shown to
      improve multiple metabolic parameters in patients with type 2 diabetes. However,
      its role in the prevention of atherosclerosis progression is uncertain. STUDY
      DESIGN: VeIn-Coronary aTherOsclerosis and Rosiglitazone after bypass surgerY
      (VICTORY) is a cardiometabolic trial in which patients with type 2 diabetes, one
      to 10 years after CABG, will be randomly assigned to receive rosiglitazone (up to
      8 mg/day) or a placebo after qualifying angiography and intravascular ultrasound
      of a segment of one vein graft with or without a native anastomosed coronary
      artery. A comprehensive set of athero-thrombo-inflammatory markers will be
      serially assessed during the 12-month follow-up period. Body fat distribution and
      body composition will be assessed by computed tomography and dual energy x-ray
      absorptiometry, respectively, at baseline, six months and 12 months follow-up.
      For atherosclerosis progression evaluation, repeat angiography and intravascular
      ultrasound will be performed after 12 months follow-up. The primary end point of
      the study will be the change in atherosclerotic plaque volume in a 40 mm or
      longer segment of one vein graft. CONCLUSIONS: The VICTORY trial is the first
      cardiometabolic study to evaluate the antiatherosclerotic and metabolic effects
      of rosiglitazone in post-CABG patients with type 2 diabetes.

PMID- 19746241
TI  - The utility of fragmented QRS complexes to predict significant intraventricular
      dyssynchrony in nonischemic dilated cardiomyopathy patients with a narrow QRS
      interval.
AB  - BACKGROUND: Fragmented QRS complexes in the electrocardiograms (ECGs) of patients
      with coronary artery disease are associated with adverse cardiac events. However,
      there are limited data on its predictive usefulness in patients with nonischemic
      dilated cardiomyopathy. Left ventricular dyssynchrony is common in heart failure
      patients who have wide QRS intervals, but its frequency in patients with narrow
      QRS intervals is uncertain. OBJECTIVES: To investigate the relationship between
      fragmented QRS complexes and intraventricular dyssynchrony in patients with
      nonischemic dilated cardiomyopathy in sinus rhythm. METHODS: Sixty nonischemic
      dilated cardiomyopathy patients with sinus rhythm and narrow QRS intervals were
      recruited. Forty patients had a fragmented QRS in their basal ECG, and 20
      patients did not have a fragmented QRS. Patients were analyzed for correlation
      between fragmented QRS complexes and intraventricular dyssynchrony. RESULTS: The
      maximal difference in time to the peak myocardial systolic velocity between any
      two left ventricular segments (Max-ASE Sys), and maximal difference between Max
      ASE Sys and the mean value of all segments (Max-ASE to Mean Sys) were
      significantly higher in patients with fragmented QRS complexes (P=0.001 and
      P=0.003, respectively). Seventy-two per cent of the patients with fragmented QRS
      complexes had significant left ventricular dyssynchrony; 15% of patients without
      fragmented QRS complexes had significant left ventricular dyssynchrony
      (P<0.0001). The presence of fragmented QRS complexes in leads corresponding to
      the specific ventricular segment in basal ECG was found to detect
      intraventricular dyssynchrony with 90.6% sensitivity (negative predictive value
      of 85%). CONCLUSION: Fragmentation in the resting ECG is associated with
      significant intraventricular dyssynchrony in patients with nonischemic
      cardiomyopathy, narrow QRS and sinus rhythm. Fragmentation in ECG might be useful
      in identifying patients who could benefit from cardiac resynchronization therapy.

PMID- 19746242
TI  - Treatment with spironolactone for 24 weeks decreases the level of matrix
      metalloproteinases and improves cardiac function in patients with chronic heart
      failure of ischemic etiology.
AB  - BACKGROUND: The myocardial extracellular matrix is believed to be central to the
      remodelling that takes place following myocardial infarction. The contribution of
      markers of collagen metabolism to this process remains less well understood. The
      present study examined the contribution of some of the markers of collagen
      metabolism in cardiac remodelling, as well as the effect of spironolactone on the
      remodelling process. OBJECTIVES: To investigate the pathological contribution of
      markers of collagen metabolism, including matrix metalloproteinases (MMPs),
      tissue inhibitors of metalloproteinases (TIMPs), type I collagen carboxyterminal
      telopeptide (ICTP) and procollagen type I carboxyterminal propeptide (PICP), in
      cardiac remodelling following ischemic cardiomyopathy, and to examine the
      pharmacoregulatory effects of spironolactone on collagen metabolism. METHOD:
      Eighty-six consecutive patients (62 men and 24 women) with chronic heart failure
      of ischemic etiology (patient group) and 25 age-matched controls were enrolled in
      the study. The subjects in the patient group were randomly assigned into a
      spironolactone or nonspironolactone group. Plasma levels of MMP-9, TIMP-1, ICTP
      and PICP were measured using ELISA and radioimmunoassay techniques. Furthermore,
      left ventricular diastolic diameter and ejection fraction were assessed using two
      dimensional and Doppler echocardiography. RESULTS: The plasma concentrations of
      MMP-9, TIMP-1 and the MMP-9 to TIMP-1 ratio, as well as ICTP, were significantly
      increased in the patient group. The PICP to ICTP ratio in the patient group was
      significantly lower than that in the age-matched control subjects. After a follow
      up period of 24 weeks, the PICP to ICTP ratio increased, and MMP-9, TIMP-1 and
      the MMP-9 to TIMP-1 ratio decreased in the spironolactone subgroup. CONCLUSIONS:
      Biomarkers of collagen degradation were elevated and correlated with depressed
      heart function; spironolactone may partially reverse the dysregulation in
      collagen metabolism.

PMID- 19746243
TI  - A winter's tale: report from the First Annual Canadian Biomarkers and Surrogate
      Endpoints Symposium.

PMID- 19746244
TI  - Transitioning from 16-slice to 64-slice multidetector computed tomography for the
      assessment of coronary artery disease: are we really making progress?
AB  - BACKGROUND: Multidetector computed tomography (MDCT) has demonstrated promise in
      the noninvasive evaluation of coronary artery disease. OBJECTIVE: To
      systematically review the literature regarding the improved diagnostic accuracy
      of 64-slice MDCT. METHODS: An EMBASE, OVID, PubMed and Cochrane Library database
      search was performed using the key words 'computed tomography' matched with the
      terms 'coronary artery' or 'coronary angiography' to identify English-language
      articles examining MDCT cardiac imaging. Studies that compared 16-slice or 64
      slice MDCT with catheter-based coronary angiography for the detection of coronary
      artery disease in nonrevascularized, poststent and post-coronary artery bypass
      graft patients were included. Data were pooled to obtain a weighted sensitivity,
      specificity and diagnostic accuracy for MDCT. Negative and positive predictive
      values, and likelihood ratios were calculated based on sensitivity and
      specificity. RESULTS: Currently, 15 studies involving 1008 patients have examined
      the efficacy of 64-slice MDCT in the assessment of coronary artery stenosis (more
      than 50% luminal narrowing). In these studies, 64-slice MDCT has demonstrated a
      sensitivity (89%), specificity (96%) and diagnostic accuracy (95%) similar to
      that of 16-slice MDCT. However, 64-slice MDCT was able to assess 5% more coronary
      artery segments than 16-slice MDCT. In revascularized patients, MDCT can
      accurately assess both bypass graft occlusion and stenosis. The 64-slice MDCT is
      also capable of adequately detecting in-stent restenosis. Improvements in spatial
      and temporal resolution with 64-slice technology have decreased the occurrence of
      high attenuation and motion artefacts that plagued the previous generation of
      MDCT scanners. CONCLUSION: MDCT offers an accurate assessment of the coronary
      arteries, stented arteries and bypass grafts. The improved accuracy and safety of
      MDCT may reduce the need for catheter-based coronary angiography.

PMID- 19746245
TI  - Coronary-subclavian steal syndrome.

PMID- 19746246
TI  - The level of knowledge of risk factors for peripheral arterial disease also
      depends on subjects' individual clinical situations.

PMID- 19746247
TI  - Functional health status of adolescents after the Fontan procedure -- comparison
      with their siblings.
AB  - BACKGROUND: Studies have suggested that patients who have undergone the Fontan
      procedure experience lower functional health status and diminished exercise
      capacity compared with other children. OBJECTIVES: To compare the functional
      health status of Fontan patients with and without siblings, assess whether there
      are any differences between Fontan patients and their siblings, and determine
      associated factors. METHODS: A cross-sectional, single-centre, observational
      study was performed on Fontan patients 10 to 20 years of age, and their sibling
      closest in age, followed in a tertiary pediatric hospital. Functional health
      status was measured by the Child Health Questionnaire Child Form and the
      Pediatric Quality of Life Inventory. RESULTS: A total of 68 patients and 38
      siblings were enrolled. Patients with siblings scored significantly lower on
      numerous domains of physical functional status than those without siblings.
      Compared with their matched siblings, Fontan patients reported significantly
      lower scores in all domains of the Pediatric Quality of Life Inventory and on
      physical (but not psychosocial) domains of the Child Health Questionnaire Child
      Form. Factors associated with increased patient-sibling differences included
      younger patient age, female sex, intracardiac lateral tunnel Fontan connection
      and lower ejection fraction at the time of study enrollment. CONCLUSIONS:
      Adolescents with Fontan physiology reported a lower functional health status in
      physical domains than their siblings, but had similar status in psychosocial
      domains. Having a sibling was associated with lower reported functional health
      status, suggesting an important effect of self-perceived physical limitations
      over true limitations.

PMID- 19746248
TI  - Role of ankle-brachial pressure index as a predictor of coronary artery disease
      severity in patients with diabetes mellitus.
AB  - BACKGROUND: Previous studies have reported a close correlation between low ankle
      brachial pressure index (ABPI) and various cardiovascular risk factors. However,
      despite the well-established potential hazards of consequent coronary artery
      disease (CAD), no data exist on the relationship between ABPI and the severity of
      CAD, particularly in patients with diabetes mellitus (DM). METHODS: A total of
      840 patients ranging from 35 to 87 years of age (mean [+/- SD] 63.9+/-10.2 years)
      with suspected CAD in a clinical practice were enrolled. All patients underwent
      ABPI measurements and coronary angiography. Patients were divided into four
      groups according to the results of ABPI measurements and the presence or absence
      of DM: group A had an ABPI value of at least 0.9 but no DM (A-/D-); group B had
      an ABPI value of at least 0.9 and DM (A-/D+); group C had an ABPI of less than
      0.9 but no DM (A+/D-); and group D had an ABPI value of less than 0.9 and DM
      (A+/D+). RESULTS: Age was significantly higher in the A+ (groups C and D) than
      the A- patients (groups A and B). Moreover, men predominated in all four groups.
      Comparisons of sex distribution among the four groups revealed that group D had
      the highest percentage of women, while group A had the lowest. Total cholesterol
      level did not differ among the four groups, although group D tended to have the
      highest result. Patients in group D had the highest percentages of hypertension,
      hypercholesterol, hypertriglyceride, low high-density lipoprotein cholesterol and
      high low-density lipoprotein cholesterol among the four groups. Group D exhibited
      the highest triglyceride and uric acid levels, the lowest high-density
      lipoprotein cholesterol level, and the highest metabolic syndrome criteria number
      and percentage of metabolic syndrome. Furthermore, group D had the highest mean
      lesion numbers, mean numbers of target vessel involvement, stenoses with type C
      classification and complex morphology lesions (chronic total occlusion, diffuse
      or calcified lesions) among the four groups. There were still significant
      differences in lesion numbers (P<0.001) and numbers of target vessel involvement
      (P<0.001) for ABPI predicting CAD severity after controlling for the effects of
      DM and age. The sensitivity, specificity, positive predictive value and negative
      predictive value of using an ABPI of less than 0.9 to predict CAD differed
      significantly between patients with and without DM. CONCLUSIONS: ABPI is a useful
      noninvasive tool for predicting CAD severity, even in patients with DM.

PMID- 19746249
TI  - Heart failure clinics are associated with clinical benefit in both tertiary and
      community care settings: data from the Improving Cardiovascular Outcomes in Nova
      Scotia (ICONS) registry.
AB  - BACKGROUND: Heart failure (HF) clinics are known to improve outcomes of patients
      with HF. Studies have been limited to single, usually tertiary centres whose
      experience may not apply to the general HF population. OBJECTIVES: To determine
      the effectiveness of HF clinics in reducing death or all-cause rehospitalization
      in a real-world population. METHODS: A retrospective analysis of the Improving
      Cardiovascular Outcomes in Nova Scotia (ICONS) disease registry was performed.
      All 8731 patients with a diagnosis of HF (844 managed in HF clinics) who were
      discharged from the hospital between October 15, 1997, and July 1, 2000, were
      identified. Patients enrolled in any one of four HF clinics (two community-based
      and two academic-based) were compared with those who were not. The primary
      outcome was the one-year combined hospitalization and mortality. RESULTS:
      Patients followed in HF clinics were younger (68 versus 75 years), more likely to
      be men (63% versus 48%), and had a lower ejection fraction (35% versus 44%),
      lower systolic blood pressure (137 mmHg verus 146 mmHg) and lower serum
      creatinine (121 micromol/L versus 130 micromol/L). There was no difference in the
      prevalence of hypertension (56%), diabetes (35%) or stroke/transient ischemic
      attack (16%). The one-year mortality rate was 23%, while 31% of patients were
      rehospitalized; the combined end point was 51%. Enrollment in an HF clinic was
      independently associated with reduced risk of total mortality (hazard ratio [HR]
      0.69 [95% CI 0.51 to 0.90], P=0.008; number needed to treat for one year to
      prevent the occurrence of one event [NNT]=16), all-cause hospital readmission (HR
      0.27 [95% CI 0.21 to 0.36], P<0.0001; NNT=4), and combined mortality or hospital
      readmission (HR 0.73 [95% CI 0.60 to 0.89], P<0.0015; NNT=5). DISCUSSION: HF
      clinics are associated with reductions in rehospitalization and mortality in an
      unselected HF population, independent of whether they are academic- or community
      based. Such clinics should be made widely available to the HF population.

PMID- 19746250
TI  - Nocturnal blood pressure profiles among normotensive, controlled hypertensive and
      refractory hypertensive subjects.
AB  - BACKGROUND: Nocturnal blood pressure abnormalities are independently associated
      with an increased risk of death and cardiovascular disease. It is unclear,
      however, whether they are related to the presence or severity of hypertension.
      OBJECTIVES: To determine and compare the prevalence of sleep pattern disturbances
      in normotensive (NT) and hypertensive patients. METHODS: The present cross
      sectional study assessed the nocturnal blood pressure profiles from 24 h
      ambulatory blood pressure monitoring of refractory hypertensive (RH) (n=26),
      controlled hypertensive (CH) (n=52) and NT (n=52) subjects who were matched for
      age, sex and body mass index. Results are expressed as mean +/- SD or proportion,
      as appropriate. RESULTS: During sleep, the percentage fall in mean arterial
      pressure was 15.1+/-6.1% in the NT group, 11.5+/-7.0% in the CH group and 7.7+/
      7.7% in the RH group (P<0.0001). The corresponding proportions of nondipping were
      25.0%, 42.3% and 61.5%, respectively (P=0.006), and those of nocturnal
      hypertension were 9.6%, 23.1% and 84.6%, respectively (P<0.0001). All pairwise
      comparisons of nocturnal blood pressure fall were significant. The proportion of
      subjects in the RH group who experienced a rise in nocturnal blood pressure
      (19.2%) was significantly greater than the proportions in the NT and CH groups
      (P=0.001), as was the proportion of subjects with nocturnal hypertension
      (P<0.0001). There was less extreme dipping in RH, although the difference was not
      statistically significant (P=0.08). CONCLUSIONS: A significantly higher
      prevalence of nondipping, nocturnal hypertension and nocturnal blood pressure
      rising in RH was demonstrated. These sleep disturbances or independently, their
      cause, may account for the difficulties in attaining blood pressure control.

PMID- 19746251
TI  - Transition to adult health care for adolescents and young adults with congenital
      heart disease: perspectives of the patient, parent and health care provider.
AB  - BACKGROUND: Pediatric institutions play a large role in preparing young adults
      with congenital heart disease to transition to adult care. OBJECTIVE: To
      determine the perspectives of patients, parents and providers on transition
      preparation. METHODS: Patients aged nine to 18 years with congenital heart
      defects and their respective parent(s) participated in semistructured interviews.
      Health care providers completed a self-administered survey. RESULTS: A total of
      23 patients, 22 parents and 45 health care providers were enrolled in the study.
      Only 36% of patients demonstrated a clear understanding of transition and its
      implications for their cardiac care. Parents were extensively involved in care
      activities, with 95% accompanying their child to visits at the clinic, 68%
      staying with their child for the entire visit and 45% administering their
      medication. Children more knowledgeable about their diagnosis demonstrated a
      better understanding about their transition to adult care (100% versus 7%,
      respectively; P<0.01) and were more likely to communicate directly with their
      providers than those who were less or not knowledgeable (88% versus 33%,
      respectively; P=0.03). Nurses were more likely than physicians to view increased
      parental involvement in care activities as a barrier to transition preparation
      (37% versus 5%, respectively; P=0.02). CONCLUSIONS: A lack of clear role
      expectations indicates a need for the pediatric health care setting to adapt
      appropriately to address the shifting needs of adolescent and young adult
      patients and their families. A formalized approach to transition preparation for
      adolescents with congenital heart disease needs to emphasize comprehensive
      education. A delegation of explicit responsibilities and the clear definition of
      roles for parents, providers and patients are necessary to provide young adults
      with the resources and support necessary to achieve a successful transition to
      adult care.

PMID- 19746252
TI  - Evaluating the views of paramedics, cardiologists, emergency department
      physicians and nurses on advanced prehospital management of acute ST elevation
      myocardial infarction.
AB  - BACKGROUND: Although advanced prehospital management (PHM) in ST elevation
      myocardial infarction (STEMI) reduces reperfusion delay and improves patient
      outcomes, its use in North America remains uncommon. Understanding perceived
      barriers to and facilitators of PHM implementation may support the expansion of
      programs, with associated patient benefit. OBJECTIVE: To explore the attitudes
      and beliefs of paramedics, cardiologists, emergency physicians and nurses
      regarding these issues. METHODS: To maximize the potential to identify
      unpredictable issues within each of the four groups, focus group sessions were
      recorded, transcribed and analyzed for themes using the constant comparative
      method. RESULTS: All 18 participants believed that PHM of STEMI decreased time to
      treatment and improved health outcomes. Despite agreeing that most paramedics
      were capable of providing PHM, regular maintenance of competence and medical
      overview were emphasized. Significant variations in perceptions were revealed
      regarding practical aspects of the PHM process and protocol, as well as ownership
      and responsibility of the patient. Success and failures of technology were also
      expressed. Varying arguments against a signed 'informed consent' were presented
      by the majority. CONCLUSIONS: Focus group discussions provided key insights into
      potential barriers to and facilitators of PHM in STEMI. Although all groups were
      supportive of the concept and its benefits, concerns were expressed and potential
      barriers identified. This novel body of knowledge will help elucidate future
      educational programs and protocol development, and identify future challenges to
      ensure successful PHM of STEMI, thereby reducing reperfusion delay and improving
      patient outcomes.

PMID- 19746253
TI  - Cesium chloride-induced torsades de pointes.
AB  - The chloride salt of cesium, a group 1A element, is gaining popularity as an
      alternative treatment of advanced cancers. Cesium chloride has primarily been
      used in cardiovascular research for arrhythmogenesis in animals because of its
      potassium-blocking effects. The present report describes a 45-year-old woman with
      metastatic breast cancer who experienced repeated episodes of torsades de pointes
      polymorphic ventricular tachycardia after several months of oral cesium therapy.
      There was a clear temporal relationship between cesium ingestion and the
      arrhythmia, which later resolved following discontinuation of cesium therapy.
      Serial cesium plasma and whole blood levels were measured over the ensuing six
      months and pharmacokinetic analysis was performed.

PMID- 19746254
TI  - Surgical removal of a 'nonretrievable' inferior vena cava filter: a unique case
      requiring a median sternotomy and cardiopulmonary bypass.
AB  - An unsuccessful percutaneous removal of a caval filter that required retrieval
      through a median sternotomy and cardiopulmonary bypass is reported. Surgical
      options and techniques are discussed.

PMID- 19746255
TI  - Coronary artery-middle cardiac vein fistula after endomyocardial biopsy in a
      heart transplant patient.

PMID- 19746256
TI  - Biventricular noncompaction in a patient with dextrocardia/dextroversion
      diagnosed with cardiac magnetic resonance imaging.

PMID- 19746257
TI  - Gas-forming purulent pericardial effusion.

PMID- 19746258
TI  - Cloning, molecular characterization and expression of a cDNA encoding a
      functional NADH-cytochrome b5 reductase from Mucor racemosus PTCC 5305 in E.
      coli.
AB  - The present work aims to study a new NADH-cytochrome b5 reductase (cb5r) from
      Mucor racemosus PTCC 5305. A cDNA coding for cb5r was isolated from a Mucor
      racemosus PTCC 5305 cDNA library. The nucleotide sequence of the cDNA including
      coding and sequences flanking regions was determined. The open reading frame
      starting from ATG and ending with TAG stop codon encoded 228 amino acids and
      displayed the closest similarity (73%) with Mortierella alpina cb5r. Lack of
      hydrophobic residues in the N-terminal sequence was apparent, suggesting that the
      enzyme is a soluble isoform. The coding sequence was then cloned in the pET16b
      transcription vector carrying an N-terminal-linked His-Tag sequence and expressed
      in Escherichia coli BL21 (DE3). The enzyme was then homogeneously purified by a
      metal affinity column. The recombinant Mucor enzyme was shown to have its optimal
      activity at pH and temperature of about 7.5 and 40 degrees C, respectively. The
      apparent K(m) value was calculated to be 13 microM for ferricyanide. To our
      knowledge, this is the first report on cloning and expression of a native fungal
      soluble isoform of NADH-cytochrome b5 reductase in E. coli.

PMID- 19746259
TI  - Extraction of high-quality host DNA from feces and regurgitated seeds: a useful
      tool for vertebrate ecological studies.
AB  - DNA extraction methods for genotyping non-invasive samples have led to great
      advances in molecular research for ecological studies, and have been particularly
      useful for analyzing threatened species. However, scarce amounts of fragmented
      DNA and the presence of Taq polymerase inhibitors in non-invasive samples are
      potential problems for subsequent PCR amplifications. In this study we describe a
      novel technique for extracting DNA from alimentary tract cells found on external
      surfaces of feces and regurgitated seeds. The presence of contaminants and
      inhibitors is minimized and samples are preserved intact for use in other
      ecological research (e.g. trophic studies). The amplification efficiency and
      purity of the extracted DNA from feces were significantly higher than in commonly
      used extraction procedures. Moreover, DNA of two bird species was identified from
      seeds expelled by regurgitation. Therefore, this method may be suitable for
      future ecological studies of birds, and other vertebrate groups.

PMID- 19746260
TI  - The effect of crude ethanol extract and fractions of Hyptidendron canum (Pohl ex
      Benth.) Harley on the hepatopancreas of Oreochromis niloticus L.
AB  - Hyptidendron canum (Pohl ex Benth.) Harley is a native tree of the Brazilian
      Savannah. The fish Oreochromis niloticus L. was used as an experimental model to
      determine the bioactivity of the crude ethanol extract as well as ethyl acetate,
      hexanic and chloroform fractions obtained from its leaves. The plant ethanol
      extract and fractions were administered to the fish orally with their feed.
      Twenty four hours later, the fish were sacrificed and their livers dissected,
      fixed in neutral formalin, embedded in paraffin and sectioned. Histological
      analyses were performed using Masson's trichrome and Haematoxylin-Eosin.
      Histochemical studies were performed using Feulgen, PAS (Periodic Acid Schiff)
      and PAS + salivary amylase and Sudan IV stain. The qualitative analysis of the
      material showed that both the crude ethanol extract and the fractions from H.
      canum induced vasoactive activity, causing vasodilation and vascular congestion,
      and the hexanic fraction also caused an apparent proliferation of capillaries.
      Hepatopancreas toxicity was evident through inflammatory processes. Pancreatic
      (chloroform fraction) and hepatic alterations, hemorrhagic spots and necroses
      were observed in fish treated with-ethanol extract and fractions. This study is
      the first description of the biologic action of the crude ethanol extract and the
      hexane, ethyl acetate and chloroform fractions in fish.

PMID- 19746261
TI  - Organic and inorganic selenium compounds produce different protein patterns in
      the blood plasma of rats.
AB  - Some selenium compounds offer important health benefits when administered at
      supranutritional doses, such as improvement of the immune system and of male
      fertility, and the prevention of some types of cancer. The traditional selenium
      indexes do not account for the metabolic status of this element among replete
      individuals. As a consequence, there is a need for new indexes that distinguish
      between repletion statuses of selenium. The aim of this work was to identify some
      plasmatic proteins that respond to supranutritional doses of selenium, which
      could be proposed as new protein markers of selenium intake. The effect on rats
      of dietary supplementation with either selenomethylselenocysteine (SMSeC) or
      sodium-selenate on some blood plasma proteins was investigated. Two experimental
      groups consisting of six rats each were fed a basic diet supplemented with either
      SMSeC or sodium-selenate at 1.9 microg-Se / g-diet for ten weeks. The control
      group was fed a diet that contained the recommended selenium dose (0.15 microg-Se
      / g-diet). The changes in the abundance of a group of plasmatic proteins were
      quantified and analysed statistically. Haptoglobin, apolipoprotein E and
      transthyretin increased their abundance after diet supplementation with either
      form of selenium. HNF6 was responsive only to SMSeC, whereas fibrinogen responded
      only to sodium-selenate. We postulate that the protein patterns observed in this
      work could be proposed as new molecular biology-based markers of selenium intake.

PMID- 19746262
TI  - Antioxidant properties and total phenolic content of eight Salvia species from
      Turkey.
AB  - Methanolic extracts of eight Salvia species, namely S. aethiopis, S.
      candidissima, S. limbata, S. microstegia, S. nemorosa, S. pachystachys, S.
      verticillata, and S. virgata, sampled from Eastern Anatolia in Turkey, were
      screened for their possible antioxidant activities by two complementary test
      systems, namely DPPH free radical scavenging and beta-carotene/linoleic acid.
      Total phenolic content of the extracts of Salvia species were performed Folin
      Ciocalteu reagent and gallic acid used as standard. A wide variation has been
      observed among species in terms of antioxidant activity and total phenolic
      content. In both DPPH and beta-carotene system, the most active plant was Salvia
      verticillata with a value of IC50=18.3 microg/ml and 75.8%, respectively. This
      species also has the highest total phenolic content (167.1 mgGAE/g DW). The total
      amount of phenolics was between 50.3 to 167.1 mgGAE/g DW among species. A
      positive linear correlation was observed between total phenolic content and
      antioxidant activity of the extracts. The results suggest that the extract of
      Salvia species, notably Salvia verticillata with the highest antioxidant
      activity, can be used as natural antioxidants in the food industry.

PMID- 19746263
TI  - Hormesis response of marine and freshwater luminescent bacteria to metal
      exposure.
AB  - The stimulatory effect of low concentrations of toxic chemicals on organismal
      metabolism, referred to as hormesis, has been found to be common in the widely
      used luminescence bioassay. This paper aims to study the hormesis phenomenon in
      both marine and freshwater luminescent bacteria, named Photobacterium phosphorem
      and Vibrio qinghaiensis. The effects of Cu (II), Zn (II), Cd (II) and Cr (VI) on
      luminescence of these two bacteria were studied for 0 to 75 minutes exposure by
      establishing dose- and time-response curves. A clear hormesis phenomenon was
      observed in all four testing metals at low concentrations under the condition of
      luminescence assays.

PMID- 19746264
TI  - Analysis of the intronic single nucleotide polymorphism rs#466452 of the nephrin
      gene in patients with diabetic nephropathy.
AB  - We present the analysis of an intronic polymorphism of the nephrin gene and its
      relationship to the development of diabetic nephropathy in a study of diabetes
      type 1 and type 2 patients. The frequency of the single nucleotide polymorphism
      rs#466452 in the nephrin gene was determined in 231 patients and control
      subjects. The C/T status of the polymorphism was assessed using restriction
      enzyme digestions and the nephrin transcript from a kidney biopsy was examined.
      Association between the polymorphism and clinical parameters was evaluated using
      multivariate correspondence analysis. A bioinformatics analysis of the single
      nucleotide polymorphism rs#466452 suggested the appearance of a splicing enhancer
      sequence in intron 24 of the nephrin gene and a modification of proteins that
      bind to this sequence. However, no change in the splicing of a nephrin transcript
      from a renal biopsy was found. No association was found between the polymorphism
      and diabetes or degree of renal damage in diabetes type 1 or 2 patients. The
      single nucleotide polymorphism rs#466452 of the nephrin gene seems to be neutral
      in relation to diabetes and the development of diabetic nephropathy, and does not
      affect the splicing of a nephrin transcript, in spite of a splicing enhancer
      site.

PMID- 19746265
TI  - Biological effects of an aqueous extract of Salix alba on the survival of
      Escherichia coli AB1157 cultures submitted to the action of stannous chloride.
AB  - Stannous chloride (SnC12) is used in nuclear medicine as a reducing agent to
      obtain technetium-99m-radiopharmaceuticals. It have been reported that natural
      products might reduce the genotoxic and cytotoxic effects related to SnC12. This
      work evaluated the biological effects of an aqueous extract of Salix alba on the
      survival of Escherichia coli (E. coli) AB1157 (wild type) cultures submitted to
      the action of SnC12. E. coli AB1157 cultures (exponential growth phase) were
      collected by centrifugation, washed and resuspended in 0.9% NaCl. Samples were
      incubated in water bath shaker with: (a) SnC12 (25 microg/ml), (b) Salix alba
      extract(11.6 mg/ml) and (c) SnC12 (25 microg/ml) + Salix alba extract (11.6
      mg/ml). Incubation with 0.9% NaCl was also carried out (control). At 60 min
      intervals, aliquots were withdrawn, diluted, spread onto Petri dishes with solid
      LB medium and incubated overnight. The colonies formed were counted and the
      survival fractions calculated. The extract was not able to protect the E. coli
      cultures against the lesive action of SnC12. The extract also did not interfere
      with the survival of the cultures. It suggested that the substances present in
      the Salix alba aqueous extract did not interfere strongly with cellular
      metabolism and did not alter the survival fractions of E. coli AB 1157. It is
      speculated that this extract cannot interfere with the generation of free
      radicals, the possible main agent responsible for SnC12 lesive action.

PMID- 19746266
TI  - Defense mechanisms of Solanum tuberosum L. in response to attack by plant
      pathogenic bacteria.
AB  - The natural resistance of plants to disease is based not only on preformed
      mechanisms, but also on induced mechanisms. The defense mechanisms present in
      resistant plants may also be found in susceptible ones. This study attempted to
      analyze the metabolic alterations in plants of the potato Solanum tuberosum L.
      cv. Agata that were inoculated with the incompatible plant-pathogenic bacteria X.
      axonopodis and R. solanacearum, and the compatible bacterium E. carotovora.
      Levels of total phenolic compounds, including the flavonoid group, and the
      activities of polyphenol oxidase (PPO) and peroxidase (POX) were evaluated.
      Bacteria compatibility was evaluated by means of infiltration of tubers. The
      defense response was evaluated in the leaves of the potato plants. Leaves were
      inoculated depending on their number and location on the stem. Multiple-leaf
      inoculation was carried out on basal, intermediate, and apical leaves, and single
      inoculations on intermediate leaves. Leaves inoculated with X. axonopodis and
      with R. solanacearum showed hypersensitive responses within 24 hours post
      inoculation, whereas leaves inoculated with E. carotovora showed disease
      symptoms. Therefore, the R. solanacearum isolate used in the experiments did not
      exhibit virulence to this potato cultivar. Regardless of the bacterial
      treatments, the basal leaves showed higher PPO and POX activities and lower
      levels of total phenolic compounds and flavonoids, compared to the apical leaves.
      However, basal and intermediate leaves inoculated with R. solanacearum and X.
      axonopodis showed increases in total phenolic compounds and flavonoid levels. In
      general, multiple-leaf inoculation showed the highest levels of total phenolics
      and flavonoids, whereas the single inoculations resulted in the highest increase
      in PPO activity. The POX activity showed no significant difference between single
      and multiple-leaf inoculations. Plants inoculated with E. carotovora showed no
      significant increase in defense mechanisms such as enzyme activity and phenolic
      compounds. Therefore, resistance or susceptibility in S. tuberosum cv. Agata
      might depend on leaf age, type of inoculation performed (single or multiple), and
      the interaction between plant and pathogen.

PMID- 19746267
TI  - Analysis of the nuclear localization signal of TRF1 in non-small cell lung
      cancer.
AB  - Several studies revealed a similar down-regulation of telomeric repeat binding
      factor 1 (TRF1) in tumors. We have previously reported the TRFl expression levels
      were down-regulation in non-small cell lung cancer (NSCLC). The regulation of
      TRFl localization is proposed to be important for the function and expression.
      The nuclear localization signal (NLS) and nuclear export signal (NES) are often
      important clues to localization of protein. The objective of the present study
      was to investigate the NLS and NES of TRFl in NSCLC patients. Thirty (30)
      patients with NSCLCs had undergone radical operations in The First Affiliated
      Hospital, College of Medicine, Zhejiang University. DNA sequences of NLSs and
      NESs were amplified by PCR. The PCR products were analyzed by DNA sequencing.
      There were four NLSs of the TRFl protein, including two monopartite and two
      bipartite NLSs. The NLSs sequences were included in 337KKERRVGTPQSTKKKKESRR356.
      The exon 8 and exon 9 of TRFl DNA were covered the NLS sequences. The sequences
      of predicted NESs were 11WMLDFLCLSL86 and 174NLLKLQALAV183, respectively. The
      exon 1, exon 3 and exon 4 of TRFl were covered the NES sequences. In NSCLCs,
      there was no a mutation, deletion, or substitution in NLS and NES of TRFl. We
      conclude that the NLS and NES sequences in NSCLCs patients did not have
      mutations. Down-expression of TRFl does not indicate gene mutation of NLS and NES
      in NSCLCs.

PMID- 19746268
TI  - Some considerations about the theory of intelligent design.
AB  - The so-called theory of intelligent design (ID) has gained a growing reputation
      in the Anglo-Saxon culture, becoming a subject of public debate. The approaches
      that constitute the core of this proposal, however, have been poorly
      characterized and systematized. The three most significant authors of ID are
      certainly Michael Behe, William Dembski and Stephen Meyer. Beyond the differences
      that can be distinguished in the work of each of them, the central fact in their
      arguments is the complexity of living organisms, which according to these
      authors, escapes any kind of natural explanation. In effect, according to the
      authors of ID, the irreducible complexity that can be detected in the natural
      world would allow to infer design in a scientifically valid way, even though many
      of them prefer to remain silent regarding the identity and attributes of the
      designer. We think that under this proposal, remains a deep epistemological
      confusion, since its very structure combines methodologies that are beyond the
      scope of historical and natural evolutionary theories. We also reject the claim
      that ID is a legitimate scientific theory, because it does not exhibit the
      classical characteristics that a scientific kind of knowledge must have.

PMID- 19746269
TI  - Biological properties of the Chilean native moss Sphagnum magellanicum.
AB  - An ethanol extract prepared from the gametophyte Chilean native moss Sphagnum
      magellanicum was dried out, weighed and dissolved in distilled water. This
      extract was then assayed for its antibacterial activity against the G(-) bacteria
      Azotobacter vinelandii, Erwinia carotovora subsp. carotovora, Enterobacter
      aerogenes, Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi, Vibrio
      cholerae, and the G(+) bacteria Staphylococcus aureus subsp. aureus, and
      Streptococcus type beta. The growth of the cultures of E. carotovora subsp.
      carotovora, and V. cholerae was inhibited at a concentration of 581 microg/ml of
      extract, while the cultures of E. coli, S. typhi and Streptococcus type beta were
      inhibited at a concentration of 1.16 microg/mL of extract. The concentration of
      phenolic compounds was 4.294 mg/mL; the presence of vanillic, chlorogenic,
      syringic, caffeic, gallic, 3-4 hydrozybenzoic, p-coumaric and salicylic acids was
      identified using RP- High Pressure Liquid Chromatography.

PMID- 19746270
TI  - Effects of substrate water potential in root growth of Agave salmiana Otto ex
      Salm-Dyck seedlings.
AB  - The objective of this study was to test the hypothesis that root of maguey (Agave
      salmiana Otto ex Salm-Dyck) seedlings reacts during the first 24 h to low
      substrate water potential (PsiW), by anatomical modifications. Three-4 cm root
      length seedlings were planted in vermiculite for 24 h at PsiW between -0.03 and 
      2.35 MPa. Root dimensions, proline content and anatomy were evaluated. Substrate
      PsiW between -0.65 and -2.35 MPa did not significantly affect longitudinal root
      growth. However, proline content significantly increased from 1.6 to 2.1
      micromoles mg(-1). Significant reductions of transverse root area (41%),
      thickness of mucilage covering the epidermis (47%), thickness of epidermis
      (between 15 and 46%), area of the parenchyma (between 35 and 41%) and number of
      vessels (up to 28%) were observed with PsiW of -2.35 MPa. In contrast, thickness
      of xylem wall, diameter of xylem vessels and the number of cells of the cortex of
      the differentiation root region significantly increased (64, 17, and 97%,
      respectively). The anatomical changes associated with low substrate PsiW indicate
      a net increase of root apoplatic paths; structures involved in water conduction
      increased their diameter under low substrate PsiW conditions and anatomical
      changes occurred during the first 24 h of water stress.

PMID- 19746271
TI  - The proapoptotic activity of C-terminal domain of apoptosis-inducing factor (AIF)
      is separated from its N-terminal.
AB  - Apoptosis-inducing factor (AIF) is a mitochondrial flavoprotein that mediates
      both NADH-oxidizing and caspase-independent apoptosis. Further, the proapoptotic
      activity of AIF is located in the C-terminus of AIF, although the precise minimum
      sequence responsible for apoptosis induction remains to be investigated. In the
      present study, we generated two truncated AIFs, AIFDelta1-480-FLAG, which is a
      FLAG-tagged C-terminal peptide comprising amino acids from 481 to 613, and AIF360
      480 containing amino acids from 360 to 480 of AIF. We used confocal microscopy to
      demonstrate that both the truncated proteins are expressed and located in the
      cytoplasm of transfected cells. AIFDelta1-480 but not AIF360-480 induces
      apoptosis in transfected cells. We also found that the expression of AIFDelta1
      480 could initiate the release of cytochrome c from the mitochondria. The
      suppression of caspase-9 via siRNA blocked the proapoptotic activity of AIFDelta1
      480. Therefore, AIFDelta1-480 is sufficient for inducing caspase-9-dependent
      apoptotic signaling, probably by promoting the release of cytochrome c. At last,
      we generated a chimeric immuno-AIFDelta1-480 protein, which comprised an HER2
      antibody, a Pseudomonas exotoxin A translocation domain and AIFDelta1-480. Human
      Jurkat cells transfected with the immuno-AIFDeltal-480 gene could express and
      secrete the chimeric protein, which selectively recognize and kill HER2
      overexpressing tumor cells. Our study demonstrates the feasibility of the immuno
      AIFDeltal-480 gene as a novel approach to treating HER2-overexpressing cancers.

PMID- 19746273
TI  - [Cystatin C and adiponectin in diabetics with and without coronary artery
      disease].
AB  - BACKGROUND: Patients with type 2 diabetes have a high incidence of coronary
      artery disease, which is even higher among those with renal failure. A serum
      level of cystatin C are used to assess renal function and is a potential
      cardiovascular risk factor. Adiponectin is an anti-atherogenic factor. AIM: To
      measure cystatin C and adiponectin in type 2 diabetic patients with and without
      coronary artery disease. MATERIAL AND METHODS: Nine diabetic patients with
      coronary artery disease aged 76+/- 10 years, 20 diabetics without coronary artery
      disease aged 61 +/-5 years and 20 non diabetic subjects aged 57+/-10 years, were
      studied. RESULTS: Serum levels of cystatin C (mg/L) were 1.5 (range 0.89-219),
      0.81 (range 0.71-1.08) and 0.68 mg/L (range 055-0.75) in diabetics with and
      without coronary artery disease and controls, respectively (p <0.0001). No
      differences in adiponectin between groups and no association between cystatin C
      and adiponectin, were observed. No association between both parameters and body
      mass index orglycosilated hemoglobin Ale was observed. Cystatin C had a positive
      correlation with serum creatinine (r =0.57 p <0.001). CONCLUSIONS: Diabetics with
      coronary artery disease have higher levels of cystatin C, that are closely
      correlated with serum creatinine levels.

PMID- 19746274
TI  - [Association between cardiorespiratory fitness and cardiovascular risk factors in
      healthy individuals].
AB  - BACKGROUND: Cardio respiratory fitness (FIT) is associated with a better profile
      in most modifiable cardiovascular risk factors (RF). In Chile, sedentary
      lifestyle is highly prevalent, reaching almost 90%. AIM: To determine the
      association between FIT and traditional and emergent RF in a primary prevention
      population. MATERIAL AND METHODS: We prospectively studied 1973 subjects (36%
      women, mean age 56+/- 13 years) without history of cardiovascular disease and
      absence of ischemic changes on exercise testing. We assessed cardiovascular RF
      and determined body mass index (BMI), waist circumference, systolic and diastolic
      blood pressure, fasting blood lipids, glucose, C-reactive protein (CRP) and
      fibrinogen. FIT was measured by a Sci f-reported physical activity questionnaire
      and by a maximal treadmill exercise test, expressed in metabolic equivalents
      (METs). RESULTS: Subjects in the highest FIT according to the treadmill test had
      significantly lower BMI, waist circumference, systolic and diastolic blood
      pressure, total cholesterol, triglycerides, glucose, CRP and fibrinogen, and
      higher HDL cholesterol (adjusted by age and gender). LDL cholesterol did not show
      significant changes. The same pattern of RF (including LDL cholesterol) and CRP
      was observed when using Sci f-reported physical activity as a FIT parameter There
      was a significant association between both methods to measure FIT (p <0.0001, Chi
      square Mantel-Haenszel). CONCLUSIONS: Our findings show that a better level off
      IT, assessed by exercise testing or through Sci f report is associated with
      improved levels of traditional and emergent RF.

PMID- 19746275
TI  - [Professionalism of physicians from the point of view of physicians and
      students].
AB  - BACKGROUND: Professionalism should be included as a fundamental component in the
      curriculum of undergraduate as well as graduate students of Medicine. Future
      physicians should be aware of the attributes that a professional should possess.
      AIM: To analyze the ideal medical doctor attributes from the point of view of
      physicians and students of Medicine. MATERIAL AND METHODS: One hundred four
      physicians (MD) and 47 students answered a free association test on the
      attributes they would assign to a good physician. The test was applied via
      Internet to professionals, and students were tested in group dynamics at the
      beginning of the class on Bioethics and Professionalism. Data were processed
      according to the Lexical Availability Model (LAM) which provides quantitative as
      well as qualitative evaluations. RESULTS: The attributes with higher scores among
      MD's were honesty (0.379), regular academic updating (0.373), ability (0.325) and
      empathy (0.241). Among students, the selected attributes were excellence (0.625),
      empathy (0.511), responsibility (0.280) and ability (0.209). A general agreement
      was found among physicians and students, excepts by the fact that MD's consider
      continuing academic updating as the most important attribute. CONCLUSIONS: The
      attributes that physicians and medical students evaluate as essential in
      professionalism were identified using the LAM approach. At the beginning of the
      career, students have a definite humanistic approach to their future profession.

PMID- 19746276
TI  - [Access to social networks and health care among extremely poor people].
AB  - BACKGROUND: Extremely poor people have more problems to have access to social
      networks and health care. AIM: To evaluate the access to health services and the
      perception about these services of adults living in conditions of extreme
      poverty. MATERIAL AND METHODS: A survey was applied to 361 people living in slums
      aged 15 to 77 years (83% females), that were living in these conditions for a
      mean of 11 years. Twenty six in-depth interviews were also performed to
      prototypical subjects living in extreme poverty. RESULTS: Ten percent of subjects
      were illiterate. Sixty two percent were unsatisfied with their access to health
      services and 32% were not registered in primary health clinics. Among children of
      less than 6 years of age, 22% were delayed in their vaccination schedule and 32%
      were not withdrawing the milk delivered by the complementary feeding program of
      the clinic. The qualitative analysis revealed that the lack of access to health
      care is associated with the feeling of exclusion, mutual distrust and lack of
      resolution of health problems. CONCLUSIONS: People living in extreme poverty are
      distrustful and perceive obstacles to have access to the health care system.

PMID- 19746277
TI  - [Ethical problems in medical services from the patients' point of view].
AB  - BACKGROUND: There is a paucity of information on the perception of patients about
      ethical issues in medical practice. AIM: To determine the type and frequency of
      ethical problems perceived by patients hospitalized in public and private
      hospitals. MATERIAL AND METHODS: Eighty eight subjects aged 65 years (48% women),
      admitted to a public hospital and 44 subjects aged 59 years (52% women) admitted
      to a private clinic answered a survey about ethical problems. The main issues
      covered were medical information management, participation in decision making and
      intimacy of patients. RESULTS: Fifty three percent of patients perceived at least
      one ethical problem. Patients admitted to the public hospital perceived more
      communication and intimacy problems than their peers admitted to a private
      clinic. CONCLUSIONS: Approximately half of the interviewed patients acknowledged
      the presence of ethical problems, especially in the communication and intimacy
      areas).

PMID- 19746278
TI  - [Fecundity reduction and aging in fertile women population in the period 1990
      2004 in Chile].
AB  - BACKGROUND: Chile is in the advanced stage of demographic transition with a low
      natural growth and a progressively aging population. AIM: To analyze births by
      range of maternal age and to establish if population aging is expressed in the
      women's fertile age range. MATERIAL AND METHODS: Trend analysis of births and age
      specific birth rates in the period 1990-2004, in the Chilean women population of
      reproductive age. Raw data were obtained from the Vital Statistics Yearbooks of
      the National Institute of Statistics. Trends were studied by linear regression
      and Generalized Estimating Equation (GEE). RESULTS: The general trend of births
      descended significantly from 1999 to 2004 (r: -0.996; p <0.001). Births
      significantly decreased in the range of ages from 20 to 34 years. There was an
      increase in the range of ages from 35 to 44 and from 10 to 14 years. The age
      specific birth rate declined in all ranges, with the exception of women aged 10
      to 14 years. The number of women increased significantly at all age ranges,
      except for the 20-24 year-old range where no significant change was observed and
      the 25-29 year-old range that experienced a significant reduction. CONCLUSIONS:
      In the period from 1990 to 2004, there was a significant reduction of births and
      age-specific birth rates in Chile. There was also an increased birth rate among
      women aged 35 to 44 years and an aging of the fertile women population.

PMID- 19746279
TI  - [Prevalence of drug abuse among children in basic schools].
AB  - BACKGROUND: Peer methodology (PM) is an adaptation of the privileged access
      interviewer methodology and is used for prevalence studies. PM estimates higher
      drug consumption frequencies among school and college students than self reports,
      since it minimizes underreporting. AIM: To assess drug abuse among students using
      PM. MATERIAL AND METHODS: A random sample of 234 school students of middle and
      low-middle socioeconomic status, aged 9 to 14 years (53% women) were interviewed
      using PM about drug consumption. RESULTS: The frequency of illicit drug
      consumption during the last year was 29% and 15% during the last month (current
      consumption). The consumption of tobacco and alcohol was 20% and 18% respectively
      during the last year. The figures for the last month were 11% and 8%
      respectively. The beginning age for smoking and alcohol consumption were 11.1 +/
      1.5 and 11.3+/- 1.8 years respectively. The frequency of illicit drug consumption
      was 3.5%. Illicit drug users began illicit drug consumption at earlier ages their
      non user peers. CONCLUSIONS: There is a high frequency of illicit drug
      consumption among school age children.

PMID- 19746280
TI  - [Eating disorders inventory scores among mothers of adolescents with and without
      eating disorders].
AB  - BACKGROUND: Parents have a control role in the development and treatment of
      eating disorders among teenagers. AIM: To compare attitudes, beliefs and
      behaviors between mothers of patients with eating disorders and mothers of
      teenagers without these disorders. MATERIAL AND METHODS: Twenty one mother
      sibling pairs of adolescents with eating disorders and 15 pairs of adolescents
      without this condition, but of similar age, were studied. The eating disorders
      inventory (EDI-2), a self administered questionnaire that includes 91 items, was
      applied. RESULTS: No differences in any of the subscales of EDI-2 were observed
      between mothers of teenagers with or without eating disorders. No differences in
      perfectionism, maturity fears, impulsivity and interpersonal distrust were
      observed between adolescents with and without eating disorders. The latter had a
      lesser drive for thinness and inefficacy. CONCLUSIONS: In this sample, no
      differences in behaviors, attitudes and beliefs about food, were observed between
      mothers of adolescents with and without eating disorders.

PMID- 19746281
TI  - [Rosenberg self-esteem scale: validation in a representative sample of Chilean
      adults].
AB  - BACKGROUND: Self-esteem is positively associated to the well being of people and
      could be a good mental health indicator. AIM: To determine the reliability and
      validity of the Rosenberg Self-esteem Scale in a Chilean adult sample. MATERIAL
      AND METHODS: The instrument was applied to 473 subjects living in the
      Metropolitan Region of Santiago, evenly distributed according to gender, age,
      educational level and income. The Neugarten Life Satisfaction index (LSI-A) was
      also applied to the sample. RESULTS: Cronbach's alpha for reliability of the
      scale was 0.754. There was no gender bias and factor analysis grouped items into
      two factors (5 positive and 5 negative). The instrument had a correlation of
      0.455 with the LSI-A. CONCLUSIONS: The Rosenberg Self-esteem Scale meets the
      criteria for validity and reliability of a quality instrument to measure self
      esteem in Chile.

PMID- 19746282
TI  - [Intravascular hypothermia for the management of Intracranial hypertension in
      acute liver failure: case report].
AB  - Acute liver failure has a mortality rate in excess of 80%. Most deaths are
      attributed to brain edema with intracranial hypertension and herniation of
      structures, where ammonium plays a major role in its generation. We report an 18
      year-old female with a fulminant hepatic failure caused by virus A infection. The
      patient developed a profound sopor and required mechanical ventilation. A CT scan
      showed the presence of brain edema and intracranial hypertension. A Raudemic
      catheter was inserted to measure intracranial pressure and brain temperature.
      Intracranial hypertension became refractory and intravascular hypothermia was
      started, reducing brain temperature to 33 degrees C. Seventy two hours later, a
      liver transplantation was performed. After testing graft perfusion, rewarming was
      started, completing 122 hours of hypothermia at 33 degrees C. The patient was
      discharged in good conditions after 69 days of hospitalization.

PMID- 19746283
TI  - [Primary vasculitis of the central nervous system: report of one case].
AB  - A primary central nervous system vasculitis is an uncommon and invalidating
      disease, which has a fatal course if left untreated. We report a 63 year-old
      woman presenting with a history of two months of cognitive impairment,
      dysarthria, gait instability and tremor. After four months of evolution a right
      hemianopsia and a flaccid paresis of upper right limb appeared. A brain biopsy
      was performed and the histological findings confirmed the suspicion of primary
      cerebral vasculitis. The patient was treated with cyclophosphamide and
      prednisone, observing a partial recovery of cognitive and motor function.

PMID- 19746284
TI  - [Coronary spasm secondary to an allergic reaction or Kounis syndrome: report of
      one case].
AB  - We report a 79 year-old mate with a history of an acute coronary syndrome
      subjected to coronary angioplasty and stent placement in the right coronary
      artery (RCA) four months ago. Since the patient continued with symptoms, a
      coronary angiography was performed. During the procedure, the patient developed a
      cutaneous allergic reaction and bronchospasm probably related to contrast media
      and a severe spasm of the RCA with inferior ST elevation in the absence of
      restenosis, that was difficult to treat. The presence of angina or an acute
      coronary syndrome and allergic reactions is known as the Kounis syndrome.

PMID- 19746285
TI  - [Cerebrotendinous xanthomatosis: report of one case].
AB  - Cerebrotendinous xanthomatosis is an inherited autosomal recessive disease caused
      by a mutation in the gene for the sterol 27-hydroxylase enzyme, which determines
      the accumulation of plasmatic cholestanol in various tissues. The natural history
      of this disease is characterized by chronic diarrhea beginning in childhood,
      cataract in youth, tendinous xanthomas in adulthood and later progressive
      neurological dysfunction manifested as dementia, psychiatric disorders,
      cerebellar, pyramidal or extra pyramidal signs or seizures. We report a 39 year
      old male with a history of diarrhea during childhood and bilateral cataracts
      requiring surgery at 20 years of age, who evolves later with psychiatric
      disorders and bilateral increased volume in Achules tendons. High levels of
      plasmatic cholestanol and magnetic resonance imaging confirmed the diagnosis of
      this disease.

PMID- 19746286
TI  - [On errors in medicine].
AB  - Errors in medical practice may seriously harm patients. This damage is not always
      attributable to the action of a doctor. We must bear in mind that all human
      activity is susceptible of errors and that the effects of those errors will
      depend on the target of such activity. Therefore the consequences of doctor's
      errors will necessarily be the patient's health and the only possible preventive
      action of professionals is to take the measures to reduce the occurrence of
      errors to a minimum. This essay is a reflection about the nature of errors in
      medicine, about when they can be attributed to the action of doctors and from
      where they arise. We therefore analyze errors in different human activities. We
      distinguish errors in science, arts and techniques. We also consider errors that
      arise from the act itself and analyze if this is the source of errors imputable
      to doctors.

PMID- 19746287
TI  - [Adipogenesis and osteoporosis].
AB  - Mesenchymal stem cells (MSCs) found in bone marrow stroma, are able to
      differentiate into osteoblasts and adipocytes, among other cellphenotypes. In
      normal bone marrow balance osteoblastic an adipocytes cell differentiation favour
      bone formation, while in osteoporosis there is an increased adipocytes content.
      Since osteoblasts and adipocytes originate from a common MSC precursor cell, here
      we discuss whether quantitative and qualitative stem cell defects may be the
      cause of alterations in the number and function of differentiated cells. This
      review analyzes some conditions that contribute to different
      osteogenic/adipogenic potentials in human bone marrow MSCs obtained from control
      and osteoporotic postmenopausal women. We analyze the protective effect exerted
      by locally generated factors like estradiol and leptin on MSCs differentiation,
      because altered bioavailability of these factors may play a role in osteoporosis.
      Osteoporotic MSCs (o-MSCs) are characterized by increased adipogenic potential as
      compared to control cells. Leptin exerted a direct protective action against
      adiposeness only in control cells. In contrast, leptin action on o-MSCs is
      hampered, suggesting that inadequate leptin action may be associated to lipid
      accumulation in bone marrow.

PMID- 19746288
TI  - [Recombinant activated factor VII for perioperative bleeding].
AB  - Recombinant activated factor VII (rFVIIa) is a new haemostatic drug, originally
      used for the treatment of patients with hemophilia A and B. At the present time
      it is used for other bleeding conditions such as the perioperative period. When
      used prophylactically there is a reduction in the number of bleeding episodes but
      no changes in the need for blood transfusion or other blood products. The adverse
      effects are arterial or venous thromboembolic events that are mostly related to
      the severity of the underlying disease of the patient and the concurrent
      administration of other haemostatic agents, rather than the use of rFVIIa. Its
      use is recommended when there is a persistent bleeding after the reposition of
      blood products and when surgical causes of bleeding have been discarded. The cost
      of the medication should also be considered before its use.

PMID- 19746289
TI  - [Vaccines against hepatitis A and B in Chile].
AB  - The mode of transmission and epidemiological approach for hepatitis A and B are
      different. However, both are preventable with vaccines whose efficacy and long
      lasting protection has been demonstrated. This review describes the secular
      tendency of both infections in Chile, their risk factors that have contributed to
      their persistence in the country and the interventions that have been carried out
      to reduce the disease burden. Although the vaccine for hepatitis B was
      incorporated to the immunization program in 2005, the vaccine for hepatitis A
      persists in the list of interventions that must be assumed with priority by the
      Ministry of Health. If Chilean health authorities pretend to reach the enteric
      disease indicators of developed countries, they must accelerate the
      epidemiological transition towards the elimination of hepatitis A.

PMID- 19746290
TI  - [The medical history of Edgar Allan Poe].

PMID- 19746291
TI  - [Algebra, calculus and geometry of contagion at the early evolution of a A (H1N1)
      pandemic spread].

PMID- 19746292
TI  - [Forensic reports].

PMID- 19746296
TI  - Milk consumption and circulating insulin-like growth factor-I level: a systematic
      literature review.
AB  - Studies suggest that the circulating insulin-like growth factor I (IGF-I) level
      is positively associated with the prostate cancer risk. The association of milk
      consumption and circulating IGF-I level has been examined in epidemiological
      studies with inconsistent results. We conducted a systematic literature review to
      summarize and quantify the current evidence for milk or dairy product consumption
      and the circulating IGF-I level. We searched relevant papers published in English
      up to March 2009 in various databases. Fifteen cross-sectional studies and eight
      randomized controlled trials were finally identified. Ten cross-sectional studies
      showed statistically positive correlation between milk consumption and the
      circulating IGF-I level. Randomized controlled trials indicated that the
      circulating IGF-I level was significantly higher in the milk intervention group.
      After meta-analysis, the weighted mean difference of the circulating IGF-I level
      was 13.8 ng/ml (95% confidence interval: 6.1-21.5 ng/ml) comparing the
      intervention group with the control group. The current evidence suggests that
      milk consumption may increase the circulating IGF-I level.

PMID- 19746297
TI  - In search of synergistic effects in antioxidant capacity of combined edible
      mushrooms.
AB  - The antioxidant activity of different edible mushrooms was evaluated considering
      the different contribution of individual and combined extracts. The radical
      scavenging capacity was evaluated through hydrogen atom transfer and single
      electron transfer reaction-based assays: DPPH radical scavenging activity and
      reducing power, respectively. The inhibition of lipid peroxidation was studied in
      lipossomes solutions by the beta-carotene-linoleate system. Three types of
      interactions (synergistic, additive and negative synergistic effects) were
      observed, synergism being the most abundant effect. Marasmius oreades is present
      in the mixtures with higher antioxidant properties and synergistic effects, while
      Cantharellus cibarius is present in the mixtures with lowest antioxidant
      properties and negative synergist effects. Two discriminant analyses were
      performed considering individual species in one case and mushroom mixtures in the
      other. The five mushroom species were clustered in five individual groups, but a
      similar result could not be obtained for the combined mushrooms, for which only
      the cases containing C. cibarius were separated in individual clusters.

PMID- 19746298
TI  - Kinematics of table tennis topspin forehands: effects of performance level and
      ball spin.
AB  - The purpose of this study was to investigate whether performance level and ball
      spin affect arm and racket kinematics of the table tennis topspin forehand. Nine
      advanced and eight intermediate male table tennis players hit topspin forehands
      against light and heavy backspins. Five high-speed video cameras were used to
      record their strokes at 200 fps. Contributions of joint rotations to the racket
      speed, the racket kinematics at ball impact, the time required for racket
      acceleration and the maximum slope of the racket speed-time curve (s(max)) were
      determined. The advanced players showed a significantly larger contribution of
      lower trunk axial rotation to the racket speed at impact and a significantly
      larger value of s(max), and tended to require a less time for racket acceleration
      than the intermediate players. The racket speed at impact was not significantly
      different between the two player groups. The players adjusted the racket face
      angle rather than the inclination of the racket path at impact to the different
      ball spins. The results suggest that the ability to accelerate the racket in less
      time in the topspin forehand against backspin balls may be an important factor
      that affects the performance level.

PMID- 19746299
TI  - The time-course of lexical and structural processes in sentence comprehension.
AB  - Online sentence comprehension involves multiple types of cognitive processes:
      lexical processes such as lexical access, which call on the user's knowledge of
      the meaning of words in the language, and structural processes such as the
      integration of incoming words into an emerging representation. In this article,
      we investigate the temporal dynamics of lexical access and syntactic integration.
      Unlike much previous work that has relied on temporary ambiguity to investigate
      this question, we manipulate the frequency of the verb in unambiguous structures
      involving a well-studied syntactic complexity manipulation (subject- vs. object
      extracted clefts). The results demonstrate that for high-frequency verbs, the
      difficulty of reading a more structurally complex object-extracted cleft
      structure relative to a less structurally complex subject-extracted cleft
      structure is largely experienced in the cleft region, whereas for low-frequency
      verbs this difficulty is largely experienced in the postcleft region. We
      interpret these results as evidence that some stages of structural processing
      follow lexical processing. Furthermore, we find evidence that structural
      processing may be delayed if lexical processing is costly, and that the delay is
      proportional to the difficulty of the lexical process. Implications of these
      results for contemporary accounts of sentence comprehension are discussed.

PMID- 19746300
TI  - Do humans produce the speed-accuracy trade-off that maximizes reward rate?
AB  - In this paper we investigate trade-offs between speed and accuracy that are
      produced by humans when confronted with a sequence of choices between two
      alternatives. We assume that the choice process is described by the drift
      diffusion model, in which the speed-accuracy trade-off is primarily controlled by
      the value of the decision threshold. We test the hypothesis that participants
      choose the decision threshold that maximizes reward rate, defined as an average
      number of rewards per unit of time. In particular, we test four predictions
      derived on the basis of this hypothesis in two behavioural experiments. The data
      from all participants of our experiments provide support only for some of the
      predictions, and on average the participants are slower and more accurate than
      predicted by reward rate maximization. However, when we limit our analysis to
      subgroups of 30-50% of participants who earned the highest overall rewards, all
      the predictions are satisfied by the data. This suggests that a substantial
      subset of participants do select decision thresholds that maximize reward rate.
      We also discuss possible reasons why the remaining participants select thresholds
      higher than optimal, including the possibility that participants optimize a
      combination of reward rate and accuracy or that they compensate for the influence
      of timing uncertainty, or both.

PMID- 19746301
TI  - Commentary: How traffic crashes were reduced in China--experience and
      difficulties.

PMID- 19746302
TI  - Toward national estimates of alcohol use disorders among drivers: results from
      the National Roadside Survey Pilot Program.
AB  - OBJECTIVE: To determine whether drivers contacted at the roadside can be screened
      for alcohol use disorders (AUDs). Secondarily, to produce preliminary estimates
      of AUDs among drivers and estimate the relationship between AUD status and BAC
      measured at the roadside. METHODS: A two-phase survey program was undertaken. In
      phase 1, 206 motorists were interviewed at the roadside using a 15-item AUD
      Survey derived from a condensed version of the AUDADIS and the AUDIT-C. One
      hundred sixty-seven of these motorists were invited, for a $25 incentive, to call
      the research team within 48 h of the roadside assessment to repeat the
      questionnaire and complete a more detailed AUD assessment. Phase 2 involved a 6
      state pilot test of the AUD Survey as an add-on to the 2005 National Roadside
      Survey Pilot Program. The setting for both phases of the survey program was US
      roadways on weekends between 10 p.m. and 3 a.m. RESULTS: Ninety-seven percent of
      all eligible drivers completed the AUD questionnaire. The correlation between
      roadside and telephone interview results was 0.3 for alcohol abuse, 0.6 for
      alcohol dependence and heavy drinking, and 0.7 for binge drinking. Alcohol abuse
      and dependence diagnoses had 0.6 and 0.7 correlations with diagnoses derived from
      the full AUDADIS and the AUDIT-C had a 0.8 correlation with the full AUDIT. There
      was also a statistically significant and positive relationship between having a
      positive BAC at the roadside and meeting criteria for heavy drinking.
      CONCLUSIONS: AUD status can be effectively measured at the roadside. The poor
      reliability for alcohol abuse is related to underreporting of drinking and
      driving during roadside assessments, compared to telephone follow-up. Other
      measures of hazardous alcohol use should be used in the roadside context to
      measure alcohol abuse.

PMID- 19746303
TI  - Ethnicity, age, and trends in alcohol-related driver fatalities in the United
      States.
AB  - OBJECTIVE: To evaluate the 8-year ethnic-specific declining trend in the
      proportion of alcohol-impaired driver deaths in the United States. METHODS: We
      used the Fatality Analysis Reporting System (FARS), which is a census of all
      fatal motor vehicle collisions occurring in public properties in all 50 states,
      the District of Columbia, and Puerto Rico since 1975. For this study we only
      focused on driver fatalities. Data on ethnicity were not included in the FARS
      database until 1999, limiting the analysis to the years 1999-2006. RESULTS: The
      proportion of alcohol-impaired driver deaths was higher among males compared to
      females, with Hispanics constituting the highest proportion in all age groups.
      During the past 8 years, only the decline in the proportion of alcohol-impaired
      driver deaths among male Hispanics 16-20 years old and male Whites 21-64 years
      old were significant. We were not able to identify any significant declining
      trend in the corresponding proportions among other age groups, or among female
      drivers, regardless of their age category. CONCLUSION: Though existing strategies
      have seemed to be successful in preventing an uptrend in alcohol-related fatal
      collisions in the country, their effectiveness in decreasing such incidents has
      been limited. Future studies should identify the factors that might influence the
      effectiveness of current anti-drunk driver policies.

PMID- 19746304
TI  - The Trail-making Test B and driver screening in the emergency department.
AB  - OBJECTIVES: Emergency departments (EDs) rarely screen for older driving safety.
      The Trail-Making Test B (TMT-B) is a neuropsychological test that may predict
      ability to drive. We sought to examine the driving patterns of older ED patients
      and the feasibility of screening patients in the ED using the TMT-B. METHODS: At
      a single ED at a tertiary care center, we administered the TMT-B and a survey of
      health status and driving habits to a convenience sample of adult (age 18 and
      older) ED patients. We excluded those with altered mentation, critical illness,
      or language barriers. The TMT-B, scored by the time of first attempt, requires
      connection of letters and numbers in sequence on paper, and a time > or = 180 s
      may suggest elevated driving risk. We compared time to complete the TMT-B among
      ED patients to published norms. RESULTS: Of 144 patients ages 18 to 95, 95
      (72.2%) were current drivers, and 91.4 percent of drivers were able to complete
      the TMT-B; 47.1 percent of drivers were older (65+), and 88.8 percent of older
      drivers rated their ability as good or excellent. In multivariate logistic
      regression, neither TMT-B performance nor being older predicted a recent
      collision. The mean TMT-B completion time was 66.1 (SD = 36.3, median = 56) s
      among drivers under age 65 and 117.5 (SD = 79.2, median = 95) s among those 65 or
      older. Approximately 1.9 percent (95% CI: 0.04-10.2) of drivers under 65 and 14.0
      percent (95% CI: 5.3-27.9%) of drivers 65 or older required 180 s or more for the
      TMT-B. Using unpaired T-tests, study TMT-B times were not significantly different
      from previously published norms except among 25- to 34-year-olds (79.2 versus
      50.7 s; p < 0.05) and 80- to 84-year-olds (223.9 versus 146.8 s; p < 0.01).
      CONCLUSIONS: Many older ED patients drive, and relatively healthy ED patients are
      able to complete the TMT-B with results similar to standard nomograms. The TMT-B
      may prove useful as part of targeted driver screening programs in EDs.

PMID- 19746305
TI  - Analysis of large truck rollover crashes.
AB  - OBJECTIVES: Close to a tenth of all large truck crashes result from rolling over
      during some maneuver. The aim of this study was to identify causes of these
      serious events as well as preventive measures that could be taken to reduce their
      number. METHODS: Detailed descriptions of 231 rollovers provided by field
      investigators were analyzed to identify causes. The descriptions addressed crash
      location, the nature of the crash, effect upon the vehicles involved, injuries
      and treatment, and contributing conditions. Causes were inferred from the nature
      of the crash. RESULTS: Almost half of the rollover crashes resulted from failing
      to adjust speed to curves, loads, brake condition, road surfaces, and
      intersections. A second major contributor involved lack of attention, including
      general inattention, misdirected attention, falling asleep, and distraction. The
      third major factor involved control errors, including oversteering,
      understeering, overcorrecting for errors, and minor control errors. The remainder
      were not driving errors and included those of other drivers, those occurring
      before the truck took to the road, and the condition of the vehicle before it was
      driven. CONCLUSIONS: Although they account for but a tenth of all large truck
      crashes, rollovers result from causes that are relatively unique to the vehicle
      and where it is driven. Programs could improve safety through the use of video to
      expose truck drivers to the situations causing rollovers, along with simulation
      allowing drivers to experience the consequences of errors without the harmful
      results of actual rollovers.

PMID- 19746306
TI  - Belt use: comparison of NASS-CDS and police crash reports.
AB  - OBJECTIVE: This study compares belt use in police reports with NASS-CDS
      investigator-determined belt use. The NASS-CDS cases were analyzed by severity of
      occupant injury and the crash type. METHODS: 1993-2007 NASS-CDS was analyzed for
      occupant injury severity and crash type. Light vehicles were included with model
      year 1994+. Injury severity was subdivided by MAIS 0, 1-2, 3, 4+F, and fatal.
      Crash types were frontal, side, rear, and rollover. The NASS-CDS determination of
      belt use was assumed the gold standard used to determine miscoding by the police.
      RESULTS: The fraction of unbelted occupants increased with the severity of injury
      from 3.8 percent with no injury to 53.9 percent with fatalities in the police
      reports. NASS-CDS reported no belt use of 7.9 percent (2.18 times greater than
      the police) with no injury to 58.2 percent (1.08 times) with fatalities. In side
      impacts, severely injured occupants were unbelted in 46.9 percent of NASS-CDS
      cases. This was 1.35 times greater than the 34.7 percent unbelted reported by the
      police. For severely injured occupants (MAIS 4+F), 18.4 percent of the police
      reported cases with belt use were actually unbelted occupants by NASS-CDS. The
      reporting error decreased to 5.0 percent for uninjured occupants (MAIS 0). For
      uninjured occupants, 35.7 percent of the police-reported cases of no belt use
      were coded as belted by NASS after inspecting the belt system. This difference
      decreased to 2.6 percent for fatally injured occupants. CONCLUSIONS: For
      occupants with serious-to-fatal injury, the error in police reporting belt use
      was 13-18 percent. The police often rely on self-reported belt use, which
      overestimates actual belt wearing and they do not always conduct in-depth
      investigation of vehicle, seat belt, and occupant injury to reach a conclusion of
      belt use. The police generally overreport belt use in motor vehicle crashes.

PMID- 19746307
TI  - The Health Belief Model variables as predictors of risky driving behaviors among
      commuters in Yazd, Iran.
AB  - BACKGROUND: Road traffic injuries are a major but neglected global public health
      problem. The human factor appears in the literature as the most prevalent
      contributing factor of road traffic crashes. The purpose of the study was to
      utilize components of the Health Belief Model to predict risky driving behaviors
      among a sample of commuters in Yazd, Iran. METHODS: A cross-sectional,
      correlational design was employed. A two-stage cluster sampling was used to
      recruit 300 drivers to participate in the study. RESULTS: The most reported risky
      driving behavior was speaking with others and using a cell phone, both while
      driving. There was a negative statistically significant association between risky
      driving behaviors and age. The occurrence of risky driving behaviors was higher
      among males as well as single drivers and was inversely related to education
      level. There was also a positive statistically significant correlation between
      risky driving behaviors and road traffic accidents and the number of traffic
      citations/fines. Perceived severity, susceptibility, barriers, threat, and net
      benefits were significantly related to risky driving behaviors. CONCLUSION: The
      pattern of risky driving behaviors, and safe driving barriers among commuters in
      Yazd, Iran, which are identified in this study, could be used in planning
      effective intervention programs to improve the driving habits of the commuters.
      The results of the study showed that Health Belief Model can be used as a
      conceptual framework for intervention programs aimed at decreasing road traffic
      accidents.

PMID- 19746308
TI  - Use of car crashes resulting in fatal and serious injuries to analyze a safe road
      transport system model and to identify system weaknesses.
AB  - OBJECTIVE: The objective of this study was to evaluate a model for a safe road
      transport system, based on some safety performance indicators regarding the road
      user, the vehicle, and the road, by using crashes with fatally and seriously
      injured car occupants. The study also aimed to evaluate whether the model could
      be used to identify system weaknesses and components (road user, vehicles, and
      road) where improvements would yield the highest potential for further reductions
      in serious injuries. METHODS: Real-life car crashes with serious injury outcomes
      (Maximum Abbreviated Injury Scale 2+) were classified according to the vehicle's
      safety rating by Euro NCAP (European New Car Assessment Programme) and whether
      the vehicle was fitted with ESC (Electronic Stability Control). For each crash,
      the road was also classified according to EuroRAP (European Road Assessment
      Programme) criteria, and human behavior in terms of speeding, seat belt use, and
      driving under the influence of alcohol/drugs. Each crash was compared and
      classified according to the model criteria. Crashes where the safety criteria
      were not met in more than one of the 3 components were reclassified to identify
      whether all the components were correlated to the injury outcome. In-depth crash
      injury data collected by the UK On The Spot (OTS) accident investigation project
      was used in this study. All crashes in the OTS database occurring between 2000
      and 2005 with a car occupant with injury rated MAIS2+ were included, for a total
      of 101 crashes with 120 occupants. RESULTS: It was possible to classify 90
      percent of the crashes according to the model. Eighty-six percent of the
      occupants were injured when more than one of the 3 components were noncompliant
      with the safety criteria. These cases were reclassified to identify whether all
      of the components were correlated to the injury outcome. In 39 of the total 108
      cases, at least two components were still seen to interact. The remaining cases
      were only related to one of the safety criteria, namely, the road user (26), the
      vehicle (19), and the road (24). The criteria for the road and the vehicle did
      not address multiple event crashes, rear-end crashes, hitting stationary/parked
      vehicles, or trailers. CONCLUSIONS: The model for a safe road transport system
      was found useful to classify fatal and serious road vehicle crashes. It was
      possible to classify 90 percent of the crashes according to the safety road
      transport model. For all these cases it was possible to identify weaknesses and
      parts of the road transport system with the highest potential to prevent fatal
      and serious injuries. Injury outcomes were mostly related to an interaction
      between the 3 components: the road, the vehicle, and the road user.

PMID- 19746309
TI  - Comparison of distributions of key predictor variables in CIREN and NASS-CDS
      cases meeting CIREN inclusion criteria.
AB  - OBJECTIVE: The Crash Injury Research and Engineering Network (CIREN) database
      contains data from occupants who are seriously injured in motor vehicle crashes.
      Because of the number of injured occupants and the level of detail in CIREN, a
      number of previous studies have attempted to use CIREN data to estimate injury
      risk or relative risk by comparing the frequencies of CIREN occupants with an
      injury of interest to those without that injury. However, these comparisons
      provide little useful information because CIREN case occupants cannot provide the
      control and exposure information that is needed to appropriately estimate injury
      risk. One potential source of exposure/control information for CIREN is the
      database established by the National Automotive Sampling System-Crashworthiness
      Data System (NASS-CDS). However, using NASS-CDS for this purpose requires that
      NASS-CDS and CIREN cases are drawn from the same source population. The objective
      of this article is to assess whether this requirement is met. METHODS: Occupants
      from NASS-CDS that meet CIREN inclusion criteria, termed CIREN-eligible NASS-CDS
      cases, were selected to represent the source population for CIREN. These CDS
      cases were compared to CIREN cases on a number of key variables that are used in
      many analyses of crash injury data. Comparisons were evaluated using chi-square
      tests. RESULTS: The comparisons indicate that CIREN cases are similar to CIREN
      eligible NASS-CDS cases on most variables, with some important exceptions. First,
      CIREN contains more frontal crashes than CIREN-eligible NASS-CDS. Second, there
      are fewer CIREN cases with two or more AIS 2 injuries and no AIS 3+ injuries than
      would be expected based on CIREN-eligible NASS-CDS. Finally, on average,
      occupants in CIREN have a greater number of AIS 3+ injuries, are less often
      belted in the front seat, and tend to be in higher severity crashes than
      occupants in CIREN eligible NASS-CDS. DISCUSSION: These differences suggest that
      analyses aimed at estimating either relative risk of injury by comparing CIREN
      cases to base rates from NASS-CDS, or estimating risk of injury using control
      information from NASS-CDS, should be limited to a specific crash type and injury
      definition, and should only be performed for AIS 3+ injuries. In addition,
      analyses should account for the greater overall crash and injury severity of
      CIREN cases, at least in interpretation of the results.

PMID- 19746310
TI  - The impact of replacing heavy passenger vehicles (LTVs and SUVs) in the British
      Columbia fleet with lighter versions.
AB  - OBJECTIVE: The study reported in this article addressed the potential safety
      impact of consumer movement toward smaller vehicle choices by examining the
      makeup of the full British Columbia (BC) vehicle fleet--from smaller cars to
      heavy commercial vehicles. The basic assumption made was that some operators of
      heavy light trucks/vans (LTVs) or sport utility vehicles (SUVs) would, in the
      short term, be induced to downsize to lighter vehicles of the same type. METHOD:
      The 2000-2007 BC crash-claim data at the Insurance Corporation of British
      Columbia (ICBC) was used to create matrices of average information by culpable
      and nonculpable entities in two-vehicle collisions in 15 weight categories.
      Models for the effects of various driver/crash characteristics on injury
      potential were created and used to adjust the effect calculated solely on the
      basis of weight change. Levels of heavy LTV/SUV replacement from 0.05 to 0.95 of
      the current population were tested and the redistribution of vehicles was done in
      such a way that the relationship between small-large vehicle injury ratio and
      large-small vehicle mass ratio over the whole fleet remained constant as did the
      relative proportions of culpable and nonculpable involvements. RESULTS: The net
      effect of downsizing in the manner assumed for this study was mildly positive in
      terms of overall injury risk--that is, downsizing resulted in slightly fewer
      total injuries--but not in the case of fatalities, which tended to be increased
      by a more substantial margin. However, the results showed that even replacing
      substantial proportions of the heavy LTV/SUV population would not result in a
      large impact on safety. CONCLUSIONS: Replacing almost all the heavy LTV/SUVs with
      lighter versions should reduce injuries by less than 1 percent and increase
      fatalities by 3.5 percent percent. Nevertheless, in terms of persons impacted and
      the associated costs, the effects would be noticeable. The issue for policy
      makers is to judge how the environmental benefits associated with encouraging
      such change compare with the net costs in terms of safety outcomes.

PMID- 19746311
TI  - Child safety in vehicles: validation of a mathematical model and development of
      restraint system design guidelines for 3-year-olds through mathematical
      simulations.
AB  - OBJECTIVE: The objectives of this study are to validate a mathematical simulation
      model of the Q3 ATD in an integrated forward-facing booster-type restraint in the
      rear seat and to evaluate restraint parameters to further develop design
      guidelines for this type of restraint system for forward-facing children
      corresponding to the size of the Q3. Only frontal impact was considered. METHODS:
      The software MADYMO was used to create and run the model of the restraint system
      and model of the child. The restraint system consisted of a seat and a safety
      belt. The child dummy model was the Q3. The complete model was validated to sled
      tests on 12 response signals: displacements of the dummy model, safety belt
      forces, and dummy model accelerations. The method used in the evaluation of the
      restraint parameters was a factorial design of experiments (DOE). The study
      included a total of 9 parameters: 6 related to the safety belt, such as
      pretensioner, load limiter, and belt anchor positions; two parameters related to
      the seat (stiffness and pitch angle); and one related to the foot support. The
      parameters were evaluated based on their effect on a number of dummy model
      responses. RESULTS: The validation study showed that the mathematical model
      predicted the ATD's kinematics and measurements. Furthermore, the parameters that
      had the greatest effect on the dummy model responses were the lap belt angle, the
      D-ring x and y positions (upper belt anchor), the retractor pretensioner, and the
      retractor load limiter. The lap belt angle had the greatest effects of all
      parameters. The resulting head x displacement was 7.8 cm shorter with a lap belt
      angle of 24 degrees to the horizontal, compared to a 73 degrees to the horizontal
      belt angle; it also resulted in a reduction of the head resultant acceleration by
      9.8 g. CONCLUSIONS: In order to decrease the Q3 ATD head, chest, and pelvis
      accelerations and to limit the Q3 ATD head displacement, the following practices
      are recommended: first, position the D-ring rearward of the ATD so that the belt
      encloses the ATD's shoulder; second, position the lap belt anchors to make the
      lap belt angle 24 degrees to the horizontal, but make sure submarining is not
      induced; and finally, use a safety belt with pretensioner and load limiter
      functions. However, these recommendations need to be balanced with the
      recommendations for other occupant sizes, and any specific settings have to be
      evaluated further before introduction into vehicles.

PMID- 19746312
TI  - The effectiveness of antilock brake systems on motorcycles in reducing real-life
      crashes and injuries.
AB  - This study set out to evaluate the effectiveness of antilock brake system (ABS)
      technology on motorcycles in reducing real-life injury crashes and to mitigate
      injury severity. The study comprised an analysis of in-depth fatal crash data in
      Sweden during 2005-2008 to investigate the potential of ABS as well an estimate
      of the effectiveness of ABS in crash reduction in Sweden between 2003 and 2008
      using induced exposure methods. Findings show that head-on collisions were the
      least ABS-affected crash types and collisions at intersections the most
      influenced. Induced exposure analysis showed that the overall effectiveness of
      ABS was 38 percent on all crashes with injuries and 48 percent on all severe and
      fatal crashes, with a minimum effectiveness of 11 and 17 percent, respectively.
      The study recommends the fitment of ABS on all new motorcycles as soon as
      possible and that customers only purchase motorcycles with ABS.

PMID- 19746313
TI  - Importance of physical properties of the human head on head-neck injury metrics.
AB  - OBJECTIVES: To demonstrate the importance of using specimen-specific head
      physical properties in head-neck dynamics. METHODS: Eight postmortem human
      subjects were subjected to side impact. A 9-axis accelerometer package was used
      to obtain head translational accelerations. After test, the head was isolated at
      the skull base, circumference, breadth, and length were obtained, and mass,
      center of gravity, and occipital condylar locations and moments of inertia were
      determined. Using specimen-specific and gathered accelerations, 3-dimensional
      head center of gravity accelerations and forces and moments at the occipital
      condyles were computed. Head physical properties were also extracted from
      regression equations using external dimensions of each subject. Using these
      properties and gathered kinematics, above-described accelerations and forces and
      moments were computed and compared with specimen-specific results. RESULTS: Head
      masses predicted by stature and total body mass were more in close agreement with
      specimen-specific data than head masses predicted by head circumference or head
      circumference and head length. The center of gravity to the occipital condyle
      vector was shorter in the literature-based dataset than the actual specimen
      specific vector. Differences in moments of inertias between predicted and
      specimen-specific data ranged from -15 to 59 percent. Variations in peak antero
      posterior shear, lateral shear, and axial force ranged from -12 to 46 percent, 
      21 to 78 percent, and -17 to 50 percent. Differences in peak lateral moment,
      sagittal moment, and axial torque ranged from -45 to 78 percent, -86 to 327
      percent, and -96 to 112 percent. These were normalized using specimen-specific
      data. CONCLUSIONS: Considerable variations in physical properties and injury
      metrics between data obtained from literature-based regression equations and
      actual data for each specimen suggest the critical importance of specimen
      specific data to accurately describe the biodynamic response and establish
      tolerance criteria. Because neck dynamics control head kinematics (and vice
      versa), these results emphasize the need to determine physical properties of each
      specimen following impact tests.

PMID- 19746314
TI  - Optimal sensor positioning to track rib deflections from an optical system in the
      Hybrid III dummy.
AB  - OBJECTIVES: The objective of the study was to determine the optimal use of a new
      optical device, the RibEye system, intended to obtain internal ribcage
      deflections from tests using anthropomorphic test dummies. Specifically, the
      study was designed to determine the most efficacious mounting location of light
      emitting diodes (LEDs) on the ribs and sternum in the 50th percentile male Hybrid
      III dummy. METHODS: Optical signal drop-out and accuracy assessment tests were
      conducted. In the former series, symmetric antero-posterior chest compressive
      loading was accomplished using cylindrical and square indenters, and asymmetrical
      compressive loading was accomplished using unilateral offset and diagonal belt
      type loadings. LEDs were mounted to multiple ribs bilaterally at varying
      locations on the ribcage. The internal chest potentiometer available in the
      Hybrid III dummy was used. The latter series, aimed at examining the system
      accuracy, consisted of tests with LEDs mounted to the 4 corners of the sternum,
      termed sternum-mounted LED tests; rib-mounted tests wherein LEDs were mounted
      either to a specific rib or in the intercostal space of two successive ribs; rib
      mounted tests with rotated chest simulating oblique loading; and indenter-mounted
      isolated LED tests. An electro-hydraulic testing device was used to apply
      compressive loads via an indenter in all tests. Displacement profiles were
      extracted from the optical system records, drop-out evaluations were conducted,
      and the system accuracy was evaluated by comparing data from the indenter and/or
      internal chest potentiometer. RESULTS: In general, results indicated that the
      RibEye system captures rib cage deformations effectively. Under symmetric
      loading, LEDs on the sternum responded similar to the internal chest
      potentiometer. The accuracy of the system depended on the location of position of
      the LEDs on the rib, magnitude of rib deformation, and potential interference
      from internal dummy structures such as the presence of the internal chest
      potentiometer. Optimum locations for LED placement were found to be at a distance
      of 9 cm, measured along the outer curvilinear path of the rib from the mid
      sternum on either side. At this location, the system showed no signal drop-out at
      deflections representative of the United States current frontal impact Injury
      Assessment Reference Values. Signal drop-out was also depended on the type of
      loading: diagonal belt-type loading produced more signal loss. Mounting LEDs away
      from the center of the rib representing eccentric superior-inferior (z) axis
      placement also resulted in loss of accuracy. CONCLUSIONS: These controlled
      evaluations provide a fundamental understanding of the performance of the system
      as installed in the 50th percentile male Hybrid III dummy and its ability to
      measure both antero-posterior and lateral components of deflections at multiple
      ribs, including the sternum for frontal impact applications. The system may be
      optimally used to gather rib deflection data without signal drop-out under
      symmetrical and asymmetrical loadings when LEDs are mounted on the superior
      inferior centerline of the ribs with no eccentricity along the z-axis and at the
      9-cm location from the mid-sternum on either side of the ribcage and at any
      corner on the sternum to obtain sternum deflections.

PMID- 19746315
TI  - Blood screening in a southern Nigeria City: a case study with SAVAN.
AB  - OBJECTIVE: Commercial motorcycle transportation and motorbike riding in Nigeria
      is prevalent, and road traffic accidents often result. Characteristic of such
      accidents is massive blood loss, thus exerting extreme pressure on the blood bank
      for replenishment and screening. The need to galvanize the system to design a
      blood bank with minimal bureaucracy and easy access led to screening for blood
      group. A delay in accessing blood for the victims leads to higher mortality.
      METHOD: Our approach was to establish a pre-crash blood data for all auto-bike
      riders who participated in Save Accident Victims Association of Nigeria (SAVAN,
      an indigenous, nongovernmental organization) training program. Data used were
      obtained from 1250 auto-bike riders who volunteered at our workshop. Tile
      grouping method was used for the screening. RESULTS: Blood group O positive
      (54.3%) was the most common blood group type among the auto-bike riders studied,
      with A positive following at 20.3 percent, B positive at 18.8 percent, O negative
      at 3.7 percent, AB positive at 1.3 percent, B negative at 1.1 percent, and A
      negative at 0.5 percent. It was observed that none of the volunteers grouped AB
      negative. CONCLUSION: Blood group of auto-bike riders, pedestrians, passengers,
      and all potential victims should be documented in their identification card to
      facilitate blood transfusion during major crisis or disasters where the
      facilities for typing are not available.

PMID- 19746316
TI  - Endoscopic submucosal dissection for colorectal tumors: technical difficulties
      and rate of perforation.
AB  - BACKGROUND AND STUDY AIM: Endoscopic submucosal dissection (ESD) for colorectal
      tumors is not generally recommended because of the technical difficulties and
      complications, including perforation. These aspects of ESD are thoroughly
      analyzed in our retrospective study. PATIENTS AND METHODS: We studied 105
      colorectal tumors, from 100 patients, that were treated by ESD at the Kyoto
      Prefectural University of Medicine or Nara City Hospital between 2005 and 2008.
      We analyzed tumor size, operation time, rate of en bloc resection, and
      complications. In addition, we thoroughly investigated the cases of perforation.
      RESULTS: The average tumor size was 30.4 mm; average operation time, 102 min; and
      rate of en bloc resection, 88.5 %. Perforation occurred in 10.4 % of the ESD
      procedures. Of the 11 perforations, 8 were detected during ESD and treated by
      clip closure during endoscopy, while 3 were evident only on subsequent routine
      computed tomography (CT); these were also managed conservatively. A case of
      postoperative hemorrhage was also observed. CONCLUSIONS: ESD effectively achieved
      a high rate of en bloc resection. However, the perforation rate was substantial;
      hence, improvement in the ESD method is required. The outcomes of ESD, especially
      for early colorectal malignancies, need to be assessed further.

PMID- 19746317
TI  - Three-dimensional optical coherence tomography of Barrett's esophagus and buried
      glands beneath neosquamous epithelium following radiofrequency ablation.
AB  - We report three-dimensional (3D) endoscopic microscopy findings in Barrett's
      esophagus, using an endoscopic optical coherence tomography (OCT) system in one
      patient before and in one patient after radiofrequency ablation (RFA). Findings
      were compared with those in a normal patient without Barrett's esophagus. In the
      normal patient,findings were of regular flat squamous mucosa with small
      subepithelial vessels and glands. In the Barrett's esophagus patient, findings
      were of large, densely packed glands with distortion of mucosal architecture. In
      the post-RFA case, findings were of a small number of isolated glands buried
      beneath 300-500 microm of neosquamous epithelium and lamina propria. Neosquamous
      epithelium is a marker of successful ablative therapy, while buried glands may
      have potential for dysplastic progression and are difficult to detect using
      conventional methods. These results indicate a potential role of 3D-OCT
      endoscopic microscopy for follow-up, including subsurface assessment, of ablative
      treatments for Barrett's esophagus.

PMID- 19746318
TI  - Endoscopic submucosal dissection allows less-invasive curative resection for
      gastric tube cancer after esophagectomy - a case series.
AB  - Detection of early gastric tube cancers (GTCs) has increased with more detailed
      surveillance endoscopy using indigo carmine dye following esophagectomy. This
      retrospective study clarified the clinicopathological features and application of
      endoscopic submucosal dissection (ESD) for GTCs. Data collected for eight GTCs
      treated by ESD included clinical and pathological features and outcomes following
      ESD. Overall, eight GTCs were identified in seven (6.3 %) of 112 patients who
      underwent esophagectomy and gastric tube reconstruction. Almost all lesions were
      macroscopically type 0-IIa with mucosal to submucosal invasion, and seven GTCs
      were successfully resected en bloc by ESD. Submucosal invasion to > 500 microm
      was observed in one case with associated delayed perforation that was treated
      conservatively. No local recurrences of GTCs were observed. Detailed surveillance
      endoscopy using indigo carmine dye appears useful for diagnosing early-stage GTC.
      Furthermore ESD represents a feasible alternative to conventional endoscopic
      mucosal resection as a minimally invasive therapy for early-stage GTC.

PMID- 19746320
TI  - Dislocation of the temporomandibular joint during upper endoscopy without
      sedation.

PMID- 19746321
TI  - A case of esophagorespiratory fistula successfully managed with a new technique
      for esophagoscopic closure.

PMID- 19746323
TI  - Use of spiral enteroscopy in a tertiary endoscopy center: initial experience.

PMID- 19746326
TI  - [Paroxysmal and persistent atrial fibrillation: New therapy concepts for
      pulmonary vein isolation - First clinical experiences with the High Density Mesh
      Ablator (HDMA)].
AB  - BACKGROUND AND OBJECTIVES: Interventional therapy of atrial fibrillation (AF) is
      often associated with long examination- and fluoroscopy times. The use of mapping
      catheters in addition to the ablation catheter requires multiple transseptal
      sheets for left atrial access. The HDMA was introduced in 2007 for the the
      segmental and circumferentil ablation of paroxysmal atrial fibrillation. In small
      experimental study groups the new catheter system was validated for its
      electrophysiological properties. The purpose of this prospective study was to
      evaluate feasibility and safety of pulmonary vein (PV) isolation using the High
      Density Mesh Ablator (HDMA), a novel single, expandable electrode catheter for
      both mapping and radiofrequency (RF) delivery at the left atrium/PV junctions.
      PATIENTS AND METHODS: 40 patients with highly symptomatic paroxysmal AF (PAF,
      23/57,5 %) and persistent AF (CAF, 17/42,5 %) were studied. PV isolation via the
      HDMA was performed using a customized pulsed RF energy delivery program (target
      temperature 55 - 60 degrees, power 70 - 100 Watt, 600 - 1000 seconds RF
      application time/PV). RESULTS: All 158 PV in 40 patients could be mapped and
      ablated by the HDMA. Segmental PV isolation was achieved with a mean of 3,75 +/-
      1,9 RF applications for a mean of 715 +/- 375 sec. Entrance conduction block was
      obtained in 93,5 % of all PV. Mean total procedure and fluoroscopy time was 152
      +/- 34 min and 29 +/- 10 min respectively. None of the patients experienced
      severe complications. After 3 month 78 % of the patients with PAF and 41 % with
      CAF respectively were free of AF. CONCLUSIONS: In this first study of PV
      isolation using the HDMA, our findings suggest that this method is feasible, and
      yields good primary success rates. Due to single transseptal access the HDMA
      simplifies the complex procedure of AF ablation, favorably impacting procedure
      and fluoroscopy times.

PMID- 19746327
TI  - [Full-blown diseases].

PMID- 19746328
TI  - [Ears "made of stone" - unusual secondary phenomenon of undersubstituted adrenal
      insufficiency].
AB  - HISTORY AND CLINICAL FINDINGS: A 69-year-old man was admitted with cough, fever
      and dyspnea. For years, an adrenal insufficiency has been substituted with low
      dose hydrocortisone. The hypotensive and tachycardic patient exhibited remarkable
      stony hard ears. INVESTIGATIONS: Elevated inflammatory markers and the clinical
      picture point to a pulmonary focus of infection. Radiographs of the ears show
      trabecular structures as a sign of true ossification. DIAGNOSIS, TREATMENT AND
      COURSE: Addisonian crisis due to pulmonary infection was treated successfully
      with steroids, antibiotics and intravenous fluids. The auricular ossification was
      interpreted as a secondary phenomenon of undersubstituted adrenal insufficiency.
      CONCLUSION: Adrenal insufficiency should be considered when auricular
      ossification is encountered. The pathogenesis of this phenomenon is complex and
      not well understood.

PMID- 19746329
TI  - [When eating becomes a disease - Binge-eating-disorder as comorbid eating
      disorder in obesity - Case 07/2009].
AB  - HISTORY AND ADMISSION FINDINGS: A 30-year-old obese female patient with binge
      eating behaviour, depressive symptoms and poorly regulated diabetes mellitus was
      admitted to the department of psychosomatic medicine and psychotherapy
      INVESTIGATIONS: The body mass index at time of admission was 38 kg/m(2). Fasting
      and postprandial blood glucose values were markedly increased. HbA(1c) level was
      10.2%. Psychological diagnostic showed a binge eating disorder and a major
      depressive syndrome. DIAGNOSIS, TREATMENT AND COURSE: After diagnosis, the
      patient was treated within a psychosomatic concept considering psychotherapeutic
      and diabetological aspects, including exercises and nutrition. In course of the
      treatment, the binge eating ceased and connections between binge-eating and
      depressive symptoms on the one hand as well as life story and psychiological
      conflicts on the other hand could be drawn. The poorly regulated diabetes
      improved in parallel. CONCLUSION: Given that overweight and obesity may be
      associated with somatic (e.g., diabetes mellitus) and psychic (e.g., eating
      disorder, depression) diseases, a respective screening and an interdisciplinary
      treatment are required.

PMID- 19746330
TI  - [80-year-old patient with conspicious ECG after implementation of a transvenous
      cardiac pacemaker].

PMID- 19746331
TI  - [Emergencies in hematology and oncology].

PMID- 19746332
TI  - [Angiogenesis inhibitors for treatment of angiodysplasia-related gastrointestinal
      bleeding].

PMID- 19746333
TI  - A review of venovenous and venoarterial extracorporeal membrane oxygenation in
      neonates and children.
AB  - The use of extracorporeal membrane oxygenation (ECMO) has increased since its
      inception. As this modality gained wider acceptance, its application in a variety
      of disease states has increased. The initial use of ECMO required cannulation of
      both the carotid artery and internal jugular vein (VA ECMO). Ligation of the
      carotid artery and concern regarding potential long-term sequelae prompted the
      development of the single cannula venous only (VV ECMO) technique. Various
      reports in the literature have compared VV ECMO and VA ECMO. We present a review
      of the literature with regard to both physiology and clinical application.

PMID- 19746334
TI  - Use of retrograde esophagoscopy in delayed primary esophageal anastomosis for
      isolated esophageal atresia.
AB  - INTRODUCTION: Preserving the native esophagus is critical for long-term
      swallowing function in patients with esophageal atresia (EA). However, long
      esophageal gaps and hidden distal esophageal pouches are frequently encountered,
      making primary esophageal anastomosis very difficult in cases with isolated EA.
      This study evaluates the efficacy of retrograde esophagoscopy for the
      identification of distal esophageal pouches to aid primary esophageal anastomosis
      in patients with isolated EA. MATERIAL AND METHODS: From January 1995 to January
      2007, five patients with isolated EA out of 30 patients with EA treated in our
      hospital were included in this study. All patients initially received a
      gastrostomy and distal esophagogram to evaluate distal esophageal pouches and
      esophageal gaps. Delayed esophageal reconstruction was performed 3 to 4 months
      later. During surgery for esophageal reconstruction, a 0.5 cm diameter endoscope
      was inserted through the gastrostomy to identify the distal esophageal pouch.
      RESULTS: Distal esophagograms found no distal esophageal pouch in 3 patients.
      Retrograde esophagoscopy and exploratory surgery found no distal esophageal pouch
      in only 1 patient. The esophageal gap ranged from 4 to 7 cm. All patients
      successfully received primary esophageal anastomosis except for one without a
      distal pouch who received colon interposition. Postoperative complications
      included esophageal stricture in 4 patients and gastroesophageal reflux (GER) in
      3. All esophageal strictures resolved after esophageal dilatation. One patient
      required further fundoplication for GER. CONCLUSIONS: Retrograde esophagoscopy is
      superior to distal esophagogram for the identification of distal esophageal
      pouches in isolated EA. In addition, retrograde esophagoscopy is excellent for
      the localization of distal esophageal pouches to facilitate primary end-to-end
      esophageal anastomosis.

PMID- 19746335
TI  - Lich-Gregoir ureteral reimplantation with fixation of ureter during detrusorraphy
      as a reliable outpatient anti-reflux procedure.
AB  - PURPOSE: We report our experience with a Lich-Gregoir reimplantation (LGR)
      technique that included fixation of the ureter during detrusorraphy to preserve
      the integrity of the newly created submucosal tunnel, performed as an outpatient
      anti-reflux procedure. METHODS: Ninety-seven children (mean age: 7.9 years) with
      primary VUR underwent LGR between 1995 and 2008. Twenty-one had bilateral VUR, 8
      had ureteral duplication, 9 had megaureter, and 13 had previous subureteric
      injections. Through a Pfannenstiel incision the ipsilateral ureter was mobilized
      up to the ureterovesical junction without disturbing ureterotrigonal integrity. A
      3-5 cm detrusorotomy was extended from the ureterovesical junction towards the
      umbilicus, the ureter was placed on the mucosa, and detrusorraphy was performed
      with a loosely running 3/4-0 polyglactin suture that passed through the detrusor
      on one side of the incision, taking a 1-2 mm "bite" of the ureteral adventitia,
      and detrusor on the other side. Postoperative ultrasonograms and voiding
      cystograms (VCUG) were obtained at 1 and 3 months, respectively. Children were
      then followed up for clinical symptoms of urinary tract infection with annual
      ultrasonograms. RESULTS: The mean operative time was 56 min. Eighty-one percent
      of the children were treated as outpatients. Transient voiding difficulties
      occurred in 2 children with a bilateral procedure. Reflux was cured in 116
      ureters (98%) with a mean follow-up of 58 months (range: 6-128). Ipsilateral
      obstruction was not evident during ultrasound surveillance. CONCLUSIONS: LGR is
      an outpatient procedure with a high success rate and a low morbidity. Integrity
      of the newly created submucosal tunnel is important for long-term success, which
      may be facilitated by our modified detrusorraphy technique.

PMID- 19746336
TI  - Impact of an anesthesia discharge scoring system on postoperative monitoring
      after circumcision in children: a randomized trial.
AB  - BACKGROUND: Ambulatory surgery in children, combined with new anesthetic methods,
      leads to shorter hospital stays and an increase in patient and parental
      satisfaction. AIM: Aim of the study was to determine the feasibility and safety
      of transferring children directly to the ward without a previous stay in a post
      anesthesia care unit (PACU), after undergoing circumcision for phimosis under
      regional anesthesia and non-opioid analgesia. METHODS: 187 healthy children
      undergoing circumcision were studied in a randomized manner. After surgery,
      children who met predefined inclusion criteria in the operating room were
      randomly assigned to one of two groups. Children in the first group (Group A)
      bypassed the PACU and were admitted directly to the ward, after undergoing
      assessment using the White and Song scoring system. Children in the second group
      (Group B) were first transferred to a PACU and then to the ward. The children in
      Group A who did not meet the criteria of the White and Song scoring system
      represent the level of risk associated with direct transfer to the ward and no
      PACU stay. Recovery in the PACU and the ward, parental satisfaction, number of
      readmissions and the number of parental contacts for medical problems after
      discharge were recorded and compared between the two study groups. RESULTS: 157
      children were randomly assigned into two groups (79 children in Group A and 78 in
      Group B). Demographic data, the duration of surgery, and recovery in the PACU or
      the ward were similar for the two groups. No readmissions were observed and most
      parents were very satisfied with the procedure. CONCLUSION: Children undergoing
      circumcision do not routinely require admission to a PACU and if the appropriate
      criteria are met, it is safe to transfer them directly to the ward.

PMID- 19746337
TI  - Treatment with botulinum toxin in children with chronic anal fissure.
AB  - INTRODUCTION: Chronic anal fissures with painful defecation and bloodstained
      stools can be seen in children of all ages. Constipation may precede or appear in
      connection with the symptoms. Adult patients with anal fissures have been treated
      successfully with the injection of botulinum toxin into both the internal and
      external sphincter. The effect of botulinum toxin is reversible and lasts for 3-4
      months. This pilot study attempted to examine whether botulinum toxin is also
      effective in paediatric cases of anal fissure, a treatment which not yet has been
      reported in the literature. MATERIAL AND METHODS: Six boys and seven girls aged 1
      10 years were treated with botulinum toxin (Botox ((R))) during 2002-2005 due to
      chronic anal fissure. Conventional treatment with laxatives and local
      anaesthetics had been unsuccessful in all cases. The treatment was given to five
      children under 2 years of age in a dosage of 1.25 Ux2. Eight children over 2
      years of age were given 2.5 Ux2. The injections were given in the external
      sphincter on both sides of the fissure using EMG-stimulation for guidance and
      were performed under light anaesthetics (Diprivan ((R))). Follow-up was conducted
      at 1 and 3 months after treatment. RESULTS: Within one week, 11 of the children
      were free from pain and blood stained stools, according to their parent's
      observations. One 10-year old patient initially showed some improvement but soon
      experienced a recurrence. After another injection with a higher dosage 2 months
      later, the fissure healed. One 4-year old patient did not show any signs of
      improvement. The laxatives, which had been withdrawn after the injection
      treatment, were then reinstated. At the 3 month post-treatment examination the
      patient was finally symptom-free with no signs of a fissure. There were no
      negative side-effects detected in any of the cases. Seven recurrences were noted
      in 6 of the patients after 3-30 months, often in connection with an episode of
      constipation. Repeat injections were offered and accepted by four of these
      patients, once more producing good immediate results. CONCLUSION: Treatment with
      botulinum toxin in the external sphincter produces a quick and effective
      alleviation of pain with healing of chronic anal fissures in children. The
      treatment is not considered to carry any risks but requires light anaesthesia.
      Recurrences are common after the pharmacological effect has receded but can be
      cured with an additional injection.

PMID- 19746338
TI  - Laparoscopic pancreatic resections for solid pseudopapillary tumor in children.
AB  - INTRODUCTION: The aim of this study is to investigate the effectiveness of
      laparoscopic pancreatic resections for solid pseudopapillary tumors (SPT) in
      children. PATIENTS AND METHODS: Two 13-year-old girls suffered from recurrent
      episodes of abdominal pain. Ultrasound and CT revealed a well-circumscribed
      heterogeneous mass arising from the neck of the pancreas in one and a solid
      homogeneous tumor with small cystic areas in the pancreatic tail in the other.
      Both patients underwent laparoscopic procedures. In the first case, after
      resection of the tumor a two-layer anastomosis between the distal pancreatic body
      and the posterior gastric wall was performed. In the second case, a spleen
      preserving distal pancreatectomy was carried out. Histopathological examinations
      demonstrated SPT of the pancreas in both cases. RESULTS: Both procedures were
      completed laparoscopically. The operation times were 240 min and 150 min,
      respectively. The suction drains were removed on 7th postoperative day.
      Realimentation was started on day 5. The postoperative course was uneventful.
      Control CT scans at 6 months and 2 years were normal. CONCLUSIONS: As experience
      with minimally invasive techniques continues to grow, laparoscopic pancreatic
      resections appear to be safe and feasible in children with SPT. Laparoscopic
      central pancreatectomy with distal pancreaticogastrostomy can be used to treat
      tumors of the middle pancreas. For tumors located in the pancreatic tail,
      laparoscopic spleen-preserving distal pancreatectomy may well become the approach
      of choice.

PMID- 19746339
TI  - Single incision laparoscopic surgery (SILS) in pediatric urology: decortication
      of a symptomatic renal cyst in a 14-year-old boy.

PMID- 19746340
TI  - Gastrointestinal stromal tumour of the stomach in a young child with oesophageal
      stricture.

PMID- 19746341
TI  - Exploration of inguinal canal is mandatory in cases of non palpable testis if
      laparoscopy shows elements entering a closed inguinal ring.

PMID- 19746342
TI  - [Home quarantine: buying bread is allowed].

PMID- 19746344
TI  - Renal secondary hyperparathyroidism in dogs.
AB  - The parathyroid glands secrete parathyroid hormone (PTH), which is important for
      maintaining calcium homeostasis. Parathyroid gland hyperplasia and subsequent
      hyperparathyroidism can occur secondary to chronic renal failure in dogs,
      resulting in significant alterations in calcium metabolism. Renal secondary
      hyperparathyroidism is a complex, multifactorial syndrome that involves changes
      in circulating levels of calcium, PTH, phosphorus, and 1,25
      dihydroxycholecalciferol (calcitriol). An increased PTH level can have
      deleterious effects, including soft tissue mineralization, fibrous
      osteodystrophy, bone marrow suppression, urolithiasis, and neuropathy. Dietary
      phosphorus restriction, intestinal phosphate binders, and calcitriol
      supplementation may slow the progression of renal disease and decrease PTH
      concentrations in animals with secondary hyperparathyroidism; however, the
      prognosis for these animals is guarded to poor.

PMID- 19746345
TI  - Incorporating behavioral medicine into general practice.

PMID- 19746346
TI  - 2008 Feline retrovirus management guidelines.

PMID- 19746347
TI  - Laparoscopic and laparoscopic-assisted cryptorchidectomy in dogs and cats.
AB  - There are many applications for laparoscopy in small animal surgery. A relatively
      simple one is abdominal cryptorchid castration. Laparoscopic examination of the
      peritoneal cavity can both aid in the diagnosis of abdominal cryptorchidism and
      allow treatment using either a totally laparoscopic or a laparoscopic-assisted
      technique. Minimally invasive cryptorchid castration obviates the need for "open"
      celiotomy and may thereby reduce postoperative discomfort and wound-related
      complications in these patients.

PMID- 19746348
TI  - Feline obesity: clinical recognition and management.
AB  - Obesity is one of the most common clinical problems in cats presenting to
      veterinary practitioners. Because it is a risk factor for other conditions, such
      as diabetes mellitus and hepatic lipidosis, it not only increases the morbidity
      of affected cats but may also shorten their life span. In cats, a body weight of
      greater than 20% over the ideal weight of the animal is generally accepted as
      obese. The goal of this article is to help all members of the health care team
      understand how to prevent the development of obesity in young cats and, when
      confronted with an obese adult cat, how to develop a safe and effective weight
      loss program.

PMID- 19746349
TI  - Feline nonregenerative anemia: pathophysiology and etiologies.
AB  - Nonregenerative anemia in cats results from the inability of the bone marrow to
      respond appropriately to a peripheral deficiency in RBCs. There are many causes
      of nonregenerative anemia, including primary diseases of the bone marrow and
      systemic diseases that have secondary effects on the bone marrow. The prognosis
      is variable: some etiologies are reversible, whereas others may be chronic or
      fatal.

PMID- 19746350
TI  - Limited fluid volume resuscitation.
AB  - Volume replacement therapy is crucial to the treatment of hypovolemic shock. In
      patients with certain conditions, limiting the volume of fluid administered has
      many potential therapeutic benefits and technical advantages. Hypertonic saline
      and colloids have characteristics that allow effective treatment of hypovolemic
      shock using relatively smaller volumes than would be required for isotonic
      crystalloids alone. This article describes the theory and clinical application of
      limited fluid volume resuscitation in veterinary medicine.

PMID- 19746351
TI  - Regulation of pet foods in the United States.
AB  - In the United States, pet foods (including treats, edible chews, and supplements)
      are subject to regulation at both federal and state levels. Products found to be
      adulterated or misbranded are subject to enforcement action. Veterinarians play a
      key role in helping ensure pet food safety by reporting possible adverse effects
      to authorities in a timely manner.

PMID- 19746352
TI  - Intracranial meningioma in dogs and cats: a comparative review.
AB  - Meningiomas are extraaxial tumors that arise from the arachnoid layer of the
      meninges. Seizures are the most common clinical sign in dogs; cats more often
      present with mentation changes, vision loss, and gait abnormalities. Meningiomas
      in both species grow slowly and have an insidious onset of clinical signs. These
      tumors are more likely to be malignant in dogs. Surgery, radiation, and
      chemotherapy can target the primary tumor, whereas steroids and anticonvulsants
      are confined to treating secondary effects of the tumor. Surgery is the preferred
      primary option for cats because the tumor can be excised completely in most
      cases. If the meningioma cannot be resected in its entirety, radiation therapy
      can increase survival time.

PMID- 19746353
TI  - Comparative gene expression of intestinal metabolizing enzymes.
AB  - The purpose of this study was to compare the expression profiles of drug
      metabolizing enzymes in the intestine of mouse, rat and human. Total RNA was
      isolated from the duodenum and the mRNA expression was measured using Affymetrix
      GeneChip oligonucleotide arrays. Detected genes from the intestine of mouse, rat
      and human were ca. 60% of 22690 sequences, 40% of 8739 and 47% of 12559,
      respectively. Total genes of metabolizing enzymes subjected in this study were
      95, 33 and 68 genes in mouse, rat and human, respectively. Of phase I enzymes,
      the mouse exhibited abundant gene expressions for Cyp3a25, Cyp4v3, Cyp2d26,
      followed by Cyp2b20, Cyp2c65 and Cyp4f14, whereas, the rat showed higher
      expression profiles of Cyp3a9, Cyp2b19, Cyp4f1, Cyp17a1, Cyp2d18, Cyp27a1 and
      Cyp4f6. However, the highly expressed P450 enzymes were CYP3A4, CYP3A5, CYP4F3,
      CYP2C18, CYP2C9, CYP2D6, CYP3A7, CYP11B1 and CYP2B6 in the human. For phase II
      enzymes, glucuronosyltransferase Ugt1a6, glutathione S-transferases Gstp1, Gstm3
      and Gsta2, sulfotransferase Sult1b1 and acyltransferase Dgat1 were highly
      expressed in the mouse. The rat revealed predominant expression of
      glucuronosyltransferases Ugt1a1 and Ugt1a7, sulfotransferase Sult1b1,
      acetyltransferase Dlat and acyltransferase Dgat1. On the other hand, in human,
      glucuronosyltransferases UGT2B15 and UGT2B17, glutathione S-transferases MGST3,
      GSTP1, GSTA2 and GSTM4, sulfotransferases ST1A3 and SULT1A2, acetyltransferases
      SAT1 and CRAT, and acyltransferase AGPAT2 were dominantly detected. Therefore,
      current data indicated substantial interspecies differences in the pattern of
      intestinal gene expression both for P450 enzymes and phase II drug-metabolizing
      enzymes. This genomic database is expected to improve our understanding of
      interspecies variations in estimating intestinal prehepatic clearance of oral
      drugs.

PMID- 19746354
TI  - Recent advances in the chemical synthesis of RNA.
AB  - As a consequence largely of recent developments in RNA interference (RNAi)
      research, the availability of rapid and efficient methods for the chemical
      synthesis of RNA sequences has become a matter of considerable urgency. This unit
      is concerned mainly with work that has been carried out, especially in the past
      decade, on the design of new and improved methods of RNA synthesis. The main
      criteria for the choice of protecting groups for the 2'-hydroxy functions of the
      ribonucleoside building blocks, which is arguably the most crucial strategic
      decision to be made, are discussed. A number of new ether-, acetal-, orthoester-,
      and ester-based 2'-protecting groups are described and their application, mainly
      in phosphoramidite-based solid-phase synthesis, is discussed in some detail.
      Brief consideration is also given to solution-phase RNA synthesis, which may well
      prove to be of great importance if a systemic drug is developed and multikilogram
      quantities of synthetic RNA sequences are required.

PMID- 19746355
TI  - Heat-activatable primers for hot-start PCR: oligonucleotide synthesis and basic
      PCR setup.
AB  - 2'-Deoxyribonucleoside-3'-O-(4-oxotetradec-1-yl) phosphoramidites (OXT
      phosphoramidites) are used to prepare modified oligodeoxyribonucleotide primers
      containing heat cleavable OXT phosphotriester protecting groups at 3'-ultimate
      and penultimate internucleotide linkages. The OXT-modified primers significantly
      improve performance of the polymerase chain reaction (PCR) compared to standard
      DNA primers by substantially reducing or eliminating the accumulation of PCR
      artifacts such as dimerized primers and misprimed amplicons. Basic protocols for
      synthesis of OXT-modified oligonucleotide primers and for performing hot-start
      PCR are described.

PMID- 19746356
TI  - Oligodeoxynucleotides containing N1-methyl-2'-deoxyadenosine and N6-methyl-2'
      deoxyadenosine.
AB  - This unit describes a simple and efficient synthesis of the phosphoramidite
      derivative of N(1)-methyl-2'-deoxyadenosine from 2'-deoxyadenosine. The synthesis
      starts with the monomethoxytritylation of 2'-deoxyadenosine followed by
      methylation of 5'-O-protected nucleoside at N-1. Subsequent N-chloroacetylation
      leads to N(6)-chloroacetyl-N(1)-methyl-5'-O-(p-anisyldiphenylmethyl)-2'
      deoxyadenosine, which is finally converted to its 3' phosphoramidite derivative.
      This phosphoramidite is used to incorporate N(1)-methyl-2'-deoxyadenosine into
      synthetic oligonucleotides. N-Chloroacetyl protection and controlled anhydrous
      deprotection conditions are used to avoid the Dimroth rearrangement.

PMID- 19746357
TI  - Nucleoside modification with boron clusters and their metal complexes.
AB  - General methods for the synthesis of nucleosides modified with borane clusters
      and metallacarborane complexes are presented. These include: (1) the click
      chemistry approach based on Huisgen 1,3-dipolar cycloaddition and (2) tethering
      of the metallacarborane group to the aglycone of a nucleoside via a dioxane ring
      opening in oxonium metallacarborane derivatives. The proposed methodologies
      broaden the availability of nucleoside-borane cluster conjugates and open up new
      areas for their applications.

PMID- 19746358
TI  - Production of functional bacteriorhodopsin by an Escherichia coli cell-free
      protein synthesis system supplemented with steroid detergent and lipid.
AB  - Cell-free expression has become a highly promising tool for the efficient
      production of membrane proteins. In this study, we used a dialysis-based
      Escherichia coli cell-free system for the production of a membrane protein
      actively integrated into liposomes. The membrane protein was the light-driven
      proton pump bacteriorhodopsin, consisting of seven transmembrane alpha-helices.
      The cell-free expression system in the dialysis mode was supplemented with a
      combination of a detergent and a natural lipid, phosphatidylcholine from egg
      yolk, in only the reaction mixture. By examining a variety of detergents, we
      found that the combination of a steroid detergent (digitonin, cholate, or CHAPS)
      and egg phosphatidylcholine yielded a large amount (0.3-0.7 mg/mL reaction
      mixture) of the fully functional bacteriorhodopsin. We also analyzed the process
      of functional expression in our system. The synthesized polypeptide was well
      protected from aggregation by the detergent-lipid mixed micelles and/or lipid
      disks, and was integrated into liposomes upon detergent removal by dialysis. This
      approach might be useful for the high yield production of functional membrane
      proteins.

PMID- 19746359
TI  - Studies on the synthesis and activity of three tripalladium complexes containing
      planaramine ligands.
AB  - The present study deals with the synthesis, characterization and activity against
      human cancer cell lines: A2780, A2780(cisR) and A2780(ZD0473R) of three
      tripalladium complexes, MH3, MH4 and MH5, that each have two planaramine ligands
      bound to the central metal ion. Cellular uptake levels, extent of DNA binding,
      and nature of interaction with salmon sperm and pBR322 plasmid DNA were
      determined for each complex. Palladium compounds are much more reactive than
      their corresponding platinum derivatives, which makes them therapeutically
      inactive but toxic. However, the results of the present study suggest that
      significant antitumour activity can be introduced in palladium complexes by
      lessening their reactivity by the introduction of sterically hindered ligands
      such as 2-hydroxypyridine, 3-hydroxypyridine and 4-hydroxypyridine. When bound to
      the central palladium ion, 4-hydroxypyridine appears to be more activating than 2
      hydroxypyridine and 3-hydroxypyridine, suggesting that noncovalent interactions,
      such as hydrogen bonding, may also be key determinants of antitumour activity in
      addition to the steric effect. While cisplatin binds with DNA to form intrastrand
      GG adducts that causes local bending of a DNA strand, these planaramine-derived
      palladium complexes are expected to bind with DNA and form a number of long-range
      interstrand GG adducts that would cause a global change in DNA conformation,
      provided the tripalladium cations in MH3, MH4 and MH5 persist under physiological
      conditions.

PMID- 19746360
TI  - Identification and validation of a potent type II inhibitor of inactive polo-like
      kinase 1.

PMID- 19746361
TI  - A mechanism of adsorption of beta-nicotinamide adenine dinucleotide on graphene
      sheets: experiment and theory.
AB  - Beta-nicotinamide adenine dinucleotide (NAD(+)) and its reduced form (NADH) play
      major roles in the development of electrochemical enzyme biosensors and biofuel
      cells. Unfortunately, the oxidation of NADH at carbon electrodes suffers from
      passivation of the electrodes and a decrease in passing currents. Here, we
      investigate experimentally and theoretically the reasons for such passivation.
      High-resolution X-ray photoelectron spectroscopy (HR-XPS), voltammetry, and
      amperometry show that adsorption occurs on the edges and "edge-like" defects of
      graphene sheets. HR-XPS and ab initio molecular dynamics show that the adsorption
      of NAD(+) molecules on the edges of graphene happens due to interaction with
      oxygen-containing groups such as carboxylic groups, while graphene edges
      substituted only with hydrogen are prone to passivation.

PMID- 19746362
TI  - Oxidative interception of the hydroamination pathway: a gold-catalyzed
      diamination of alkenes.
AB  - A complimentary diamination of alkenes by using homogeneous gold catalysts is
      described. The reaction is one of very few examples of homogeneous gold oxidation
      catalysis and proceeds with high selectivity under mild conditions. Individual
      steps of the suggested catalytic cycle were investigated on isolated model gold
      complexes, and new pathways for gold-catalyzed amination reactions were
      established. The key step is an intramolecular alkyl-nitrogen bond formation from
      a gold(III) intermediate. This process validates the concept of reductive
      elimination from high oxidation catalyst states for this type of C-N bond forming
      reactions.

PMID- 19746363
TI  - High-affinity inhibitors of tRNA-guanine transglycosylase replacing the function
      of a structural water cluster.
AB  - The tRNA-modifying enzyme tRNA-guanine transglycosylase (TGT) is essential for
      the pathogenic mechanism of Shigella flexneri, the causing agent of the bacterial
      diarrheal disease shigellosis. Herein, the synthesis of a new class of rationally
      designed 6-amino-imidazo[4,5-g]quinazolin-8(7H)-one- (lin-benzoguanine) based
      inhibitors of TGT are reported. In order to accommodate a small hydrophobic
      crevice opening near the binding site of ribose-34, 2-aminoethyl substituents
      were introduced in position 4 of the heterocyclic scaffold. For this purpose, a
      synthetic sequence consisting of iodination, Suzuki cross-coupling,
      hydroboration, Mitsunobu reaction, and Gabriel synthesis was employed, furnishing
      a primary amine that served as a common intermediate for the preparation of a
      series of derivatives. The resulting ligands displayed very low inhibition
      constants, down to K(i)=2 nM. Substantial additional inhibitory potency is gained
      by interaction of terminal lipophilic groups attached to the substituent at
      position 4 with the hydrophobic crevice shaped by Val45 and Leu68. At the same
      time, the secondary ammonium center in the substituent displaces a cluster of
      water molecules, solvating the catalytic residues Asp102 and Asp280, without loss
      in binding affinity. In addition, a synthetic intermediate with an unusual
      3,6,7,8,9,10-hexahydroimidazo[4,5-g][1,3]benzodiazepine core, as confirmed by X
      ray analysis, is reported.

PMID- 19746364
TI  - Vinylation of nitro-substituted indoles, quinolinones, and anilides with grignard
      reagents.
AB  - The reaction of vinyl Grignard reagents with o-methoxynitroarenes containing an
      electron-releasing substituent para to the nitro group proceeds through a pathway
      that is different from the initially expected Bartoli indole synthesis. Thus,
      instead of giving fused indole derivatives, these reactions provide a very mild
      and efficient new procedure for the synthesis of synthetically relevant aromatic
      systems containing an o-nitrovinyl moiety, such as 5-nitro-4-vinylindoles, 6
      nitro-7-vinylindoles, 6-nitro-5-vinyl-2(1H)quinolinones, and 4-nitro-3
      vinylanilines.

PMID- 19746365
TI  - Ruthenium-catalyzed dimethylamineborane dehydrogenation: stepwise metal-centered
      dehydrocyclization.

PMID- 19746366
TI  - Synthesis and characterisation of a new series of bistable iron(II) spin
      crossover 2D metal-organic frameworks.
AB  - Twelve coordination polymers with formula {Fe(3-Xpy)(2)[M(II)(CN)(4)]} (M(II):
      Ni, Pd, Pt; X: F, Cl, Br, I; py: pyridine) have been synthesised, and their
      crystal structures have been determined by single-crystal or powder X-ray
      analysis. All of the fluoro and iodo compounds, as well as the chloro derivative
      in which M(II) is Pt, crystallise in the monoclinic C2/m space group, whereas the
      rest of the chloro and all of the bromo derivatives crystallise in the
      orthorhombic Pnc2 space group. In all cases, the iron(II) atom resides in a
      pseudo-octahedral [FeN(6)] coordination core, with similar bond lengths and
      angles in the various derivatives. The major difference between the two kinds of
      structure arises from the stacking of consecutive two-dimensional {Fe(3
      Xpy)(2)[M(II)(CN)(4)]}(infinity) layers, which allows different dispositions of
      the X atoms. The fluoro and chloro derivatives undergo cooperative spin crossover
      (SCO) with significant hysteretic behaviour, whereas the rest are paramagnetic.
      The thermal hysteresis, if X is F, shifts toward room temperature without
      changing the cooperativity as the pressure increases in the interval 10(5) Pa-0.5
      GPa. At ambient pressure, the SCO phenomenon has been structurally characterised
      at different significant temperatures, and the corresponding thermodynamic
      parameters were obtained from DSC calorimetric measurements. Compound {Fe(3
      Clpy)(2)[Pd(CN)(4)]} represents a new example of a "re-entrant" two-step spin
      transition by showing the Pnma space group in the intermediate phase (IP) and the
      Pnc2 space group in the low-spin (LS) and high-spin (HS) phases.

PMID- 19746367
TI  - Crown-ether-like Pb(II)-metal framework with dual- and bimodal emissive
      properties based on its photochromic precursor by leaching.

PMID- 19746368
TI  - Azoles as reactive nucleophiles with cyclic perfluoroalkenes.
AB  - Di- and multiazole-substituted fluorocyclic products (2-13) were readily
      synthesized in good to high yields. These were synthesized by nucleophilic
      substitution reactions of perfluorocycloalkenes with azoles (i.e., imidazole,
      triazole) involving simple reaction procedures. Interestingly, these azoles were
      later found to be reactive not only with the vinylic, but also with the allylic
      fluorine atoms. This resulted in the substitution of up to six azoles on the
      fluorinated rings. Stoichiometry plays a key role in determining the degree of
      substitution. For comparison, the analogous reactions of N-substituted 1
      (trimethylsilyl)-imidazole and 1-(trimethylsilyl)-1,2,4-triazole were also
      investigated. All of the new compounds were fully characterized by elemental,
      spectral ((19)F, (1)H, (13)C NMR), and thermal differential scanning calorimetry
      (DSC) analyses.

PMID- 19746369
TI  - In-situ encapsulation of nickel particles in electrospun carbon nanofibers and
      the resultant electrochemical performance.

PMID- 19746370
TI  - Pd(II)-catalyzed condensation of a mononuclear Pt-nucleobase complex to its head
      tail dimer: characterization of a key intermediate and an end product.

PMID- 19746371
TI  - Heterogeneous catalytic oxidation by MFU-1: a cobalt(II)-containing metal-organic
      framework.

PMID- 19746372
TI  - What is cooperativity?

PMID- 19746373
TI  - Lysozyme in wine: A risk evaluation for consumers allergic to hen's egg.
AB  - Lysozyme used in wine production could present a risk for consumers allergic to
      hen's egg. Thus, precautionary labeling of lysozyme on wines has been adopted
      within the European Community by updating Annex IIIa by Directive 2007/68/EC on
      November 27, 2007. Since no scientific data is known about the actual amounts and
      risks of lysozyme in wines, various in vitro efforts and skin prick tests were
      applied in this study to evaluate the presence of lysozyme in wines and the
      reactivity of those residues in allergic individuals and to fulfill the claim of
      updating Annex IIIa announced in Directive 2003/89/EC. Depending on the wine's
      color (red or white wine) and fining with bentonite, which is known as an
      important step to remove unstable proteins mainly from white wines, diverse
      results were obtained concerning the amounts of lysozyme in finished wines and
      their in vitro and in vivo reactivity in humans allergic to hen's egg.

PMID- 19746374
TI  - Conversion of 3-aminopropionamide and 3-alkylaminopropionamides into acrylamide
      in model systems.
AB  - Carbonyl compounds have been shown to play a major role in the conversion of
      asparagine into acrylamide. However, it is unclear at this point if its role is
      only restricted to the decarboxylation of the amino acid or if carbonyl compounds
      also play a role in the deamination reaction of the decarboxylated intermediates
      3-aminopropionamide and 3-(alkylamino)propionamides. This study describes the
      deamination reaction of 3-aminopropionamide and 3-(alkylamino)propionamides
      (benzyl, phenylethyl, butyl, and octyl) in model systems and in the presence, or
      not, of different carbonyl compounds (alkadienals, alkenals, and alkanals). All
      these reactions were mainly produced at almost neutral or basic pH values. In
      addition, the reaction yields and the activation energies not only depended on
      the type of aminopropionamide involved but also on the water activity (a(w)) and
      in the presence, or not, of carbonyl compounds. However, there was not a clear
      correlation among the activation energies calculated for the different
      deamination reactions and the yields of acrylamide obtained; therefore,
      suggesting the existence of diverse pathways by which 3-aminopropionamide and 3
      (alkylamino)propionamides are converted into acrylamide. In addition, these
      reactions are also competing with other carbonyl-amine reactions when carbonyl
      compounds are present. All these results suggest that the type of the
      intermediate aminopropionamide involved is going to play a major role in both the
      amount of acrylamide produced and the conditions required for its formation. On
      the other hand, the role of carbonyl compounds in the acrylamide produced, but
      not in the activation energy of the reactions implicated, seems to be more
      limited than either the type of amine or the a(w). A detailed analysis of the
      type of the intermediate aminopropionamide formed in foods may help to define
      strategies for mitigating the formation of this food toxicant.

PMID- 19746375
TI  - In vivo, in situ tissue analysis using rapid evaporative ionization mass
      spectrometry.

PMID- 19746376
TI  - Ferromagnetic mesostructured alloys: design of ordered mesostructured alloys with
      multicomponent metals from lyotropic liquid crystals.

PMID- 19746377
TI  - Supramolecular polymers and chromonic mesophases self-organized from
      phosphorescent cationic organoplatinum(II) complexes in water.

PMID- 19746378
TI  - Flexible hybrid semiconductors with low thermal conductivity: the role of organic
      diamines.

PMID- 19746379
TI  - Potent and selective inhibition of acid sphingomyelinase by bisphosphonates.

PMID- 19746380
TI  - Janus particles with controllable patchiness and their chemical functionalization
      and supramolecular assembly.

PMID- 19746381
TI  - Asymmetric organocatalytic cascade reactions with alpha-substituted alpha,beta
      unsaturated aldehydes.

PMID- 19746382
TI  - A single slow electron triggers the loss of both chlorine atoms from the
      anticancer drug cisplatin: implications for chemoradiation therapy.

PMID- 19746383
TI  - The Newman-Kwart rearrangement of O-aryl thiocarbamates: substantial reduction in
      reaction temperatures through palladium catalysis.

PMID- 19746384
TI  - Synthesis and structural analysis of one-dimensional sp-hybridized carbon chain
      molecules.

PMID- 19746385
TI  - Ionic association of the ionic liquids [C4mim][BF4], [C4mim][PF6], and [Cnmim]Br
      in molecular solvents.
AB  - Considering the ionic nature of ionic liquids (ILs), ionic association is
      expected to be essential in solutions of ILs and to have an important influence
      on their applications. Although numerous studies have been reported for the ionic
      association behavior of ILs in solution, quantitative results are quite scarce.
      Herein, the conductivities of the ILs [Cnmim]Br (n=4, 6, 8, 10, 12),
      [C4mim][BF4], and [C4mim][PF6] in various molecular solvents (water, methanol, 1
      propanol, 1-pentanol, acetonitrile, and acetone) are determined at 298.15 K as a
      function of IL concentration. The conductance data are analyzed by the Lee
      Wheaton conductivity equation in terms of the ionic association constant (KA) and
      the limiting molar conductance (Lambda(m)(0)). Combined with the values for the
      Br- anion reported in the literature, the limiting molar conductivities and the
      transference numbers of the cations and [BF4]- and [PF6]- anions are calculated
      in the molecular solvents. It is shown that the alkyl chain length of the cations
      and type of anion affect the ionic association constants and limiting molar
      conductivities of the ILs. For a given anion (Br-), the Lambda(m)(0) values
      decrease with increasing alkyl chain length of the cations in all the molecular
      solvents, whereas the KA values of the ILs decrease in organic solvents but
      increase in water as the alkyl chain length of the cations increases. For the
      [C4mim]+ cation, the limiting molar conductivities of the ILs decrease in the
      order Br- > [BF4]- > [PF6]-, and their ionic association constants follow the
      order [BF4]- > [PF6]- > Br- in water, acetone, and acetonitrile. Furthermore, and
      similar to the classical electrolytes, a linear relationship is observed between
      ln KA of the ILs and the reciprocal of the dielectric constants of the molecular
      solvents. The ILs are solvated to a different extent by the molecular solvents,
      and ionic association is affected significantly by ionic solvation. This
      information is expected to be useful for the modulation of the IL conductance by
      the alkyl chain length of the cations, type of anion, and physical properties of
      the molecular solvents.

PMID- 19746386
TI  - Total synthesis of (+)-haplophytine.

PMID- 19746387
TI  - Structure-specific recognition of Friedreich's ataxia (GAA)n repeats by
      benzoquinoquinoxaline derivatives.
AB  - Expansion of GAA triplet repeats in intron 1 of the FXN gene reduces frataxin
      expression and causes Friedreich's ataxia. (GAA)n repeats form non-B-DNA
      structures, including triple helix H-DNA and higher-order structures (sticky
      DNA). In the proposed mechanisms of frataxin gene silencing, central unanswered
      questions involve the characterization of non-B-DNA structure(s) that are
      strongly suggested to play a role in frataxin expression. Here we examined (GAA)n
      binding by triplex-stabilizing benzoquinoquinoxaline (BQQ) and the corresponding
      triplex-DNA-cleaving BQQ-1,10-phenanthroline (BQQ-OP) compounds. We also examined
      the ability of these compounds to act as structural probes for H-DNA formation
      within higher-order structures at pathological frataxin sequences in plasmids.
      DNA-complex-formation analyses with a gel-mobility-shift assay and sequence
      specific probing of H-DNA-forming (GAA)n sequences by single-strand
      oligonucleotides and triplex-directed cleavage demonstrated that a parallel
      pyrimidine (rather than purine) triplex is the more stable motif formed at (GAA)n
      repeats under physiologically relevant conditions.

PMID- 19746388
TI  - A missing prebiotic link: discovery of a plausible synthesis of pyrimidine
      nucleotides.

PMID- 19746389
TI  - Photoswitchable fluorescent nanoparticles: preparation, properties and
      applications.
AB  - This minireview highlights recent advances of research dedicated to
      photoswitchable fluorescent nanoparticles and their applications. Recently,
      several strategies have been developed to synthesize nanoparticles with optically
      switchable emission properties: either fluorescence on/off or dual-alternating
      color fluorescence photoswitching. The underlying mechanisms of fluorescence
      photoswitching enable many different types of photoswitchable fluorescent
      nanoparticles to change fluorescence colors, thus validating the basis of the
      initial photoswitching design. Among all possible applications, the usage of
      photoswitchable fluorescent nanoparticles to empower super-resolution
      fluorescence imaging and to label biological targets was subsequently reviewed.
      Finally, we summarize the important areas regarding future research and
      development on photoswitchable fluorescent nanoparticles.

PMID- 19746390
TI  - Oligothiophene self-assembly on the surface of ZnO nanorods: toward coaxial p-n
      hybrid heterojunctions.
AB  - We describe herein the design, synthesis and detailed structural characterization
      of hybrid 1D nanostructures. They are prepared by supramolecular self-assembly of
      oligothiophene molecules on the surface of zinc oxide nanorods in solution at
      room temperature. Electronic absorption spectroscopy and X-ray diffraction show
      that both organic and inorganic components in the coaxial p-n heterojunctions are
      crystalline. Especially, it is demonstrated that the organic compounds form a
      self-assembled monolayer at the surface of the nanorods, which is not the case
      when zinc oxide quantum dots are instead used. As a result of their hybrid
      nature, the 1D nanostructures lead to ambipolar semiconducting nanostructured
      materials as active layers in field-effect transistors.

PMID- 19746391
TI  - The cage and metal effect: spectroscopy and electrochemical survey of a series of
      Sm-containing high metallofullerenes.
AB  - A series of Sm-containing high metallofullerenes, namely, Sm@C82 (I, II, III,
      IV), Sm@C84 (I, II, III), Sm@C86, Sm@C88 (I, II, III), Sm@C90 (I, II, III),
      Sm@C92 (I, II), Sm@C94 (I, II, III), and Sm@C96, is successfully synthesized and
      characterized by UV/Vis/NIR absorption spectroscopy, and cyclic and differential
      pulse voltammetry. Sm-containing high metallofullerenes have a relatively larger
      number of isomers compared with other divalent ones. The highest boiling point of
      Sm among Group II metals may be responsible for this phenomenon. Comparing the
      spectroscopic and electrochemical behaviors of Sm-containing metallofullerenes
      with those of other divalent ones, it is seen that when the size of the carbon
      cage enlarges, different structures form stable molecules with different metals.
      Furthermore, there are also some important differences in the electrochemistry
      properties. The cage effect on the electronic structures of high
      metallofullerenes is also estimated from the differences in reduction potentials
      between metallofullerenes and their corresponding fullerenes. It is believed that
      the influence of transferred electrons from the metal to the carbon cage becomes
      much weaker for high fullerenes. The redox property of high metallofullerene is
      more dependent on the carbon-cage structure than the effect of electron transfer.

PMID- 19746392
TI  - Enantioselective protonation of itaconimides with thiols and the rotational
      kinetics of the axially chiral C-N bond.
AB  - Bicyclic guanidines are able to catalyze the protonation reactions of 2
      phthalimidoacrylates with thiols in excellent yields and enantioselectivities.
      The protonation reaction of itaconimides with secondary phosphine oxides is also
      known. Herein, the tandem conjugate addition-enantioselective protonation of N
      substituted itaconimides with thiols catalyzed by chiral bicyclic guanidine is
      investigated. The rotational barrier of the C-N axis of N-2-tert-butyl
      phenylitaconimide is also studied, both experimentally and computationally.

PMID- 19746393
TI  - HPLC with polysaccharide chiral stationary phase in polar-organic phase mode:
      application to the asymmetric epoxidation of allylic alcohols.
AB  - A simple and rapid HPLC method using a polysaccharide-based chiral stationary
      phase (Chiralpak AD-H) in polar-organic phase mode has been developed for direct
      resolution of glycidyl nitrobenzoate (GNB) and 2-methyl glycidyl nitrobenzoate
      (MGNB) enantiomers. ACN and methanol were used as mobile phase and the effects of
      the addition of ethanol and 2-propanol as organic modifier in the mobile phase,
      flow rate and the column temperature were tested. The optimized conditions were:
      methanol/ethanol (80:20) at a flow rate of 0.9 mL/min and 40 degrees C. Analysis
      time was < or = 13 min and the chiral resolution was > or = 2. The method was
      validated and resulted to be selective, precise and accurate. The method was
      found to be linear in 2-300 microg/mL range (R(2) >0.999) with an LOD nearly 0.5
      microg/mL for four enantiomers. GNB and MGNB enantiomers were obtained by
      asymmetric epoxidation of allyl alcohol and 2-methyl allyl alcohol, respectively,
      using chiral titanium-tartrate complexes as catalyst and dichloromethane as
      solvent after in situ derivatization of the intermediate glycidols derivatives.
      The quite simple and rapid validated method was applied successfully for direct
      determination of the enantiomeric excess (> or = 90%) and yield obtained in real
      samples of asymmetric epoxidation of allylic alcohols without further
      purification, workup or solvent removal. The method provides a useful and value
      added tool for controlling the enantiomeric purity of the synthesized epoxides.

PMID- 19746394
TI  - Uncertainty in the determination of glucose in aqueous solutions by high
      performance liquid chromatography with evaporative light scattering detection.
AB  - The determination of glucose and other carbohydrates is the most widespread
      chemical analysis that is performed within the industries of food, beverage,
      forage, biomass, pulp and paper, pharmaceuticals among others. Besides that,
      sugar refineries need to control their products, by-products and effluents, and
      furthermore, glucose in the sucrose refining process, is considered an impurity,
      which shall be controlled. Being HPLC the most currently instrumental technique
      used for glucose analysis, the evaporative light scattering detector (ELSD)
      offers advantages (sensitivity, possibility for operating in gradient mode) over
      the also used refractive index detector. In this work, an HPLC-ELSD methodology
      was optimised and validated, aiming the estimate of the uncertainty associated
      with the results at low levels of concentration of glucose to be measured.
      Linearity of the response was obtained in the range of glucose concentrations
      from 20 to 300 mg/L, with an analysis time of 10 min. The global uncertainty was
      estimated accordingly to the bottom-up approach used by Eurachem. It was 13% on
      average for concentrations from 100 to 300 mg/L. For lower concentrations,
      uncertainty increased significantly up to 30% in the vicinity of the LOD of the
      method.

PMID- 19746395
TI  - Effects of variation in modulator temperature during cryogenic modulation in
      comprehensive two-dimensional gas chromatography.
AB  - Many modulation systems in comprehensive 2D GC (GC x GC) are based on cryogenic
      methods. High trapping temperatures in these systems can result in ineffective
      trapping of the more volatile compounds, whilst temperatures that are too low can
      prevent efficient remobilisation of some compounds. To better understand the
      trapping and release of compounds over a wide range of volatilities, we have
      investigated a number of different constant temperature modulator settings, and
      have also examined a constant temperature differential between the cryo-trap and
      the chromatographic oven. These investigations have led us to modify the
      temperature regulation capabilities of the longitudinally modulated cryogenic
      system (LMCS). In contrast to the current system, where the user sets a constant
      temperature for the cooling chamber, the user now sets the temperature difference
      between the cryo-trap and the chromatographic oven. In this configuration, the
      cooling chamber temperature increases during the chromatographic run, tracking
      the oven temperature ramp. This produces more efficient, volatility-dependent
      modulation, and increases the range of volatile compounds that can be analysed
      under optimal trap-and-release conditions within a single analytical run. This
      system also reduces cryogenic fluid consumption.

PMID- 19746396
TI  - Inherent peak compression of charged analytes in electrochromatography.
AB  - This work resolves peak compression of charged analytes in CEC with strong cation
      exchange stationary phase particles. By combining electrochromatographic peak
      shape analysis with the results of numerical simulations and confocal laser
      scanning microscopy in the packed capillaries, we identify electrical field
      induced concentration polarization as the key physical phenomenon responsible for
      the inherent existence of local electrical field gradients on the scale of an
      individual support particle. Consequently, positive and negative field gradients
      exist between and inside the particles along the whole packing. Their intensity
      depends on the particles cation-selectivity (governed by the particles volume
      charge density and the mobile phase ionic strength) and the applied field
      strength. The interplay of these local field gradients with the analytes
      retention (intraparticle adsorption) determines whether fronting, tailing, or
      spiked analyte peaks are observed, and it provides a mechanism by which strongly
      retained analytes can be eluted over long distances with little zone dispersion.
      Our analysis explains the "anomalous" peak compression effects with strong cation
      exchange particles, which have been reported more than a decade ago (Smith, N.
      W., Evans, M. B., Chromatographia 1995, 41, 197-203) and since then remained
      largely unresolved.

PMID- 19746397
TI  - MEKC determination of vanadium from mineral ore and crude petroleum oil samples
      using precapillary chelation with bis(salicylaldehyde)tetramethyl
      ethylenediimine.
AB  - An analytical procedure has been developed for the separation of Cu(II), Ni(II),
      Co(II), Fe(II), Pd(II), Th(IV), V(IV), and determination of Fe(II), Co(II),
      Ni(II), and V(IV) by MEKC after chelation with
      bis(salicylaldehyde)tetramethylethylenediimine (H(2)SA(2)Ten). Uncoated fused
      silica capillary was used with an applied voltage of 30 kV with photo-diode array
      detection at 228 nm. SDS was added as micellar medium at pH 8.2 with sodium
      tetraborate buffer (0.1 M). Linear calibrations were established within 0.015
      1000 microg/mL of each element with LOD within 5-67 ng/mL. The method was applied
      for the determination of vanadium from crude oil and ore samples in the range
      0.34-2.40 and 114.2-720.7 microg/g with RSD 1.7-3.8 and 0.98-2.30% (n = 3),
      respectively. Fe, Ni, and Co present in crude oil and ore samples were also
      determined with RSD 1.3-2.8, 1.1-4.1, and 1.2-3.5% (n = 3), respectively. The
      results were compared with that of supplier's specifications and atomic
      absorption spectrometry (AAS). Method was evaluated by standard addition
      technique.

PMID- 19746398
TI  - Capillary electrophoretic enantioseparation of m-nisoldipine using two different
      beta-cyclodextrins.
AB  - The methods for the enantioseparation of m-nisoldipine, a new 1,4-dihydropyridine
      calcium ion antagonist, were developed. The elaborated methods of m-nisoldipine
      enantiomers separation were successfully performed using an anionic CD-sulfobutyl
      ether-beta-CD (SBE-beta-CD) or carboxymethyl-beta-CD as chiral selector. However,
      the results indicated that SBE-beta-CD was a better chiral selector for
      enantioseparation of the neutral m-nisoldipine. Furthermore, comparing the two
      SBE-beta-CDs, the derivative with a higher degree of substitution (DS) of 7.0
      induced better enantioresolution than the one with low DS (4.0). In addition,
      possible chiral recognition mechanisms of dihydropyridines were discussed.

PMID- 19746399
TI  - Dispersive liquid-liquid microextraction using extraction solvent lighter than
      water.
AB  - For the first time a dispersive liquid-liquid microextraction method on the basis
      of an extraction solvent lighter than water was presented in this study. Three
      organophosphorus pesticides (OPPs) were selected as model compounds and the
      proposed method was carried out for their preconcentration from water samples. In
      this extraction method, a mixture of cyclohexane (extraction solvent) and acetone
      (disperser) is rapidly injected into the aqueous sample in a special vessel (see
      experimental section) by syringe. Thereby, a cloudy solution is formed. In this
      step, the OPPs are extracted into the fine droplets of cyclohexane dispersed into
      aqueous phase. After centrifuging the fine droplets of cyclohexane are collected
      on the upper of the extraction vessel. The upper phase (0.40 microL) is injected
      into the gas chromatograph (GC) for separation. Analytes were detected by a flame
      ionization detector (FID) (for high concentrations) or MS (for low
      concentrations). Some important parameters, such as the kind of extraction and
      dispersive solvents and volume of them, extraction time, temperature, and salt
      amount were investigated. Under the optimum conditions, the enrichment factors
      (EFs) ranged from 100 to 150 and extraction recoveries varied between 68 and
      105%, both of which are relatively high over those of published methods. The
      linear ranges were wide (10-100 000 microg/L for GC-FID and 0.01-1 microg/L for
      GC-MS) and LODs were low (3-4 microg/L for GC-FID and 0.003 microg/L for GC-MS).
      The RSDs for 100.0 microg/L of each OPP in water were in the range of 5.3-7.8% (n
      = 5).

PMID- 19746400
TI  - Fate of vinclozolin, thiabendazole and dimethomorph during storage, handling and
      forcing of chicory.
AB  - BACKGROUND: As part of ongoing research for a sustainable production of Belgian
      endives, the fate of three fungicides during storage, handling and forcing of
      witloof chicory roots was investigated. Storage roots are protected against
      Sclerotinia sp. Fuckel and Phoma exigua var. exigua Desm. by means of vinclozolin
      and thiabendazole respectively. During hydroponic forcing, the most imminent
      pathogen is Phytophthora cryptogea Pethybr. & Laff., which is controlled by the
      use of dimethomorph. RESULTS: Vinclozolin and thiabendazole concentrations on
      roots remained constant during storage at -1 degrees C. Dermal exposure of the
      workers in hydroponics was exceeded. Vinclozolin and thiabendazole residues were
      not detected 2 weeks after hydroponic forcing; dimethomorph was still detected at
      harvest. At harvest, the vinclozolin concentration in the chicory heads was below
      the maximum residue limit, but the chicory roots contained residues much above
      the thiabendazole and dimethomorph maximum residue level. CONCLUSION: Vinclozolin
      and thiabendazole residues applied before storage are still present on the roots
      at the start of the forcing cycle. During the set-up of chicory roots, preventive
      measures are recommended, as effects of repeated human exposure to low doses of
      applied fungicides cannot be excluded. Dimethomorph applied at the start of the
      hydroponic forcing is the only pesticide detected in the drainage water at
      harvest. The chicory heads were safe for human consumption. However, more
      attention should be paid to the residues of fungicides in the roots used for
      cattle feeding.

PMID- 19746401
TI  - Comparison of solidification of floating drop and homogenous liquid-liquid
      microextractions for the extraction of two plasticizers from the water kept in
      PET-bottles.
AB  - Two approaches based on solidification of floating drop microextraction (SFDME)
      and homogenous liquid-liquid microextraction (HLLE) were compared for the
      extraction and preconcentration of di-(2-ethylhexyl) phthalate (DEHP) and di-(2
      ethylhexyl) adipate (DEHA) from the mineral water samples. In SFDME, a floated
      drop of the mixture of acetophenone/1-undecanol (1:8) was exposed on the surface
      of the aqueous solution and extraction was permitted to occur. In HLLE, a
      homogenous ternary solvent system was used by water/methanol/chloroform and the
      phase separation phenomenon occurred by salt addition. Under the optimal
      conditions, the LODs for the two target plasticizers (DEHA and DEHP), obtained by
      SFDME-GC-FID and HLLE-GC-FID, were ranged from 0.03 to 0.01 microg/L and 0.02 to
      0.01 microg/L, respectively. HLLE provided higher preconcentration factors (472.5
      and 551.2-fold) within the shorter extraction time as well as better RSDs (4.5
      6.9%). While, in SFDME, high preconcentration factors in the range of 162-198 and
      good RSDs in the range of 5.2-9.6% were obtained. Both methods were applied for
      the analysis of two plasticizers in different water samples and two target
      plasticizers were found in the bottled mineral water after the expiring time and
      the boiling water was exposed to a polyethylene vial.

PMID- 19746402
TI  - High dose methotrexate population pharmacokinetics and Bayesian estimation in
      patients with lymphoid malignancy.
AB  - The purpose of present study was to develop a population pharmacokinetic model of
      high dose methotrexate (HD-MTX) infusion in patients with lymphoid malignancy, to
      investigate the biological and clinical covariates related to the drug
      distribution and elimination. It is also the purpose to propose a limited
      sampling strategy (LSS) for the estimation of the time above the threshold (0.2
      micromol.L(-1)). A total 82 patients with lymphoid malignancy were involved in
      the study. A pharmacokinetic model was developed using nonlinear mixed-effect
      model. The influence of demographic characteristics, biological factors, and
      concurrent administration were investigated. The final predictive performance was
      validated by bootstrap and cross-validation. Bayesian estimation was evaluated.
      The pharmacokinetics of HD-MTX was described by a two-compartment model. The
      pharmacokinetic parameters and the inter-individual variability were as follows:
      the clearance CL, 7.45 L.h(-1) (inter-individual variability 50.6%), the volume
      of the central and peripheral compartment V(1), 25.9 L (22.5%), V(2), 9.23 L
      (97.8%), respectively, and the intercompartmental clearance Q, 0.333 L.h(-1)
      (70.4%). The influence of serum creatinine on CL and weight on V(1) was retained
      in the final model. The protocol involved one sampling time at 44 h after the
      start of the infusion, allowing one to predict the time at which the MTX
      concentration reached the expected threshold (0.2 micromol.L(-1)). Serum
      creatinine and weight showed significant influence on methotrexate CL and V(1),
      respectively. Furthermore, a Bayesian estimation based on the covariates and 44 h
      sample was developed, allowing prediction of the individual methotrexate
      pharmacokinetic parameters and the time to 0.2 micromol.L(-1).

PMID- 19746403
TI  - Characterization of green-tissue protein extract from alfalfa (Medicago sativa)
      exploiting a 3-D technique.
AB  - There is a growing interest of pharmaceutical companies for plant-based
      production systems. To facilitate the general acceptance of plants as
      bioreactors, the establishment of efficient downstream operations is critical. It
      has been proposed that a better understanding of the properties of the
      contaminant proteins can benefit downstream processing design and operation. The
      coupled application of 2-DE with aqueous two-phase partitioning has been
      suggested as a practical 3-D method to characterize potential contaminant
      proteins from plant extracts. The application of this novel 3-D approach to a
      complex protein extract from alfalfa (Medicago sativa) containing a model
      recombinant protein (human granulocyte colony stimulating factor (hG-CSF))
      resulted in the quantification of 55 protein spots. The 3-D properties (M(r), pI,
      and K(p)) obtained for 17 proteins comprising 69% of the alfalfa proteins,
      allowed the proposal of a prefractionation step as well as the identification of
      the target molecule (rG-CSF) from bulk of alfalfa proteins. The information
      obtained from this experimental approach was useful for the identification of the
      potential contaminant proteins that will occur in alfalfa when this plant is used
      as a host for recombinant proteins. Additionally, this method will assist in the
      design of adequate purification strategies for recombinant proteins expressed in
      alfalfa green tissue.

PMID- 19746406
TI  - The influence of combinations of oximes on the reactivating and therapeutic
      efficacy of antidotal treatment of tabun poisoning in rats and mice.
AB  - The influence of the combination of oximes on the reactivating and therapeutic
      efficacy of antidotal treament of acute tabun poisoning was evaluated. The
      ability of two combinations of oximes (HI-6 + obidoxime and HI-6 + K203) to
      reactivate tabun-inhibited acetylcholinesterase and reduce acute toxicity of
      tabun was compared with the reactivating and therapeutic efficacy of antidotal
      treatment involving single oxime (HI-6, obidoxime, K203) using in vivo methods.
      Studies determining percentage of reactivation of tabun-inhibited blood and
      tissue acetylcholinesterase in poisoned rats showed that the reactivating
      efficacy of both combinations of oximes is higher than the reactivating efficacy
      of the most effective individual oxime in blood and diaphragm and comparable with
      the reactivating effects of the most effective individual oxime in brain.
      Moreover, both combinations of oximes were found to be slightly more efficacious
      in the reduction of acute lethal toxic effects in tabun-poisoned mice than the
      antidotal treatment involving individual oxime. A comparison of reactivating and
      therapeutic efficacy of individual oximes showed that the newly developed oxime
      K203 is slightly more effective than commonly used obidoxime and both of them are
      markedly more effective than the oxime HI-6. Based on the obtained data, we can
      conclude that the antidotal treatment involving chosen combinations of oximes
      brings beneficial effects for the potency of antidotal treatment to reactivate
      tabun-inhibited acetylcholinesterase in rats and to reduce acute toxicity of
      tabun in mice.

PMID- 19746407
TI  - Types of article published in physiotherapy journals: a quantitative analysis.
AB  - BACKGROUND AND PURPOSE: The aim of this study was to quantify and assess the
      types of research and review articles published in physiotherapy professional
      journals with international circulations. METHOD: Selected articles from nine
      physiotherapy journals in a period of five years were classified according to
      their study design. RESULTS: A total number of 1627 articles were included in
      this study of which 205 (12.60%) were randomized controlled trial (RCT). Articles
      published with the highest frequency were 'observational/descriptive studies' (n
      = 305, 18.75%), whereas 'meta-analyses' were the rarest ones (n = 21, 1.29%).
      Many articles were validation studies (n = 216, 13.28%) and articles classified
      as 'others' (n = 217, 13.34%). High heterogeneity was found in terms of
      distribution over years and journals with an improvement of the number of RCTs
      among years. CONCLUSION: The distribution of different types of article in
      physiotherapy journals is similar to other disciplines. The improvement of RCTs
      represents an important move in the right direction for evidence-based
      physiotherapy research.

PMID- 19746408
TI  - A novel zebrafish mutant with wavy-notochord: an effective biological index for
      monitoring the copper pollution of water from natural resources.
AB  - We identified a novel zebrafish mutant that has wavy-notochord phenotypes, such
      as severely twisted notochord and posterior malformations, but has normal
      melanocytes. Histological evidences showed that proliferating vacuolar cells
      extended their growth to the muscle region, and consequently caused the wavy
      notochord phenotypes. Interestingly, those malformations can be greatly reversed
      by exposure with copper, suggesting that copper plays an important role on wavy
      notochord phenotypes. In addition, after long-term copper exposure, the surviving
      larvae derived from wavy-notochord mutants displayed bone malformations, such as
      twisted axial skeleton and osteophyte. These phenotypic changes and molecular
      evidences of wavy-notochord mutants are highly similar to those embryos whose
      lysyl oxidases activities have been inactivated. Taken together, we propose that
      (i) the putative mutated genes of this wavy-notochord mutant might be highly
      associated with the lysyl oxidase genes in zebrafish; and (ii) this fish model is
      an effective tool for monitoring copper pollution of water from natural
      resources.

PMID- 19746409
TI  - Are recently identified genetic variants regulating BMI in the general population
      associated with anorexia nervosa?
AB  - The influence of body mass index (BMI) on susceptibility to anorexia nervosa (AN)
      is not clear. Recently published genome-wide association (GWA) studies of the
      general population identified several variants influencing BMI. We genotyped
      these variants in an AN sample to test for association and to investigate a
      combined effect of BMI-increasing alleles (as determined in the original GWA
      studies) on the risk of developing the disease. Individual single nucleotide
      polymorphisms (SNPs) were tested for association with AN in a sample of 267 AN
      patients and 1,636 population controls. A logistic regression for the combined
      effect of BMI-increasing alleles included 225 cases and 1,351 controls. We found
      no significant association between individual SNPs and AN. The analysis of a
      combined effect of BMI-increasing alleles showed absence of association with the
      investigated condition. The percentages of BMI-increasing alleles were equal
      between cases and controls. This study found no evidence that genetic variants
      regulating BMI in the general population are significantly associated with
      susceptibility to AN.

PMID- 19746410
TI  - Association between methylenetetrahydrofolate reductase (MTHFR) C677T
      polymorphism and age of onset in schizophrenia.
AB  - Different lines of evidence indicate that methylenetetrahydrofolate reductase
      (MTHFR) functional gene polymorphisms, causative in aberrant folate-homocysteine
      metabolism, are associated with increased vulnerability to several heritable
      developmental disorders. Opposing views are expressed considering the possible
      association between MTHFR and susceptibility for schizophrenia. In order to
      evaluate if age of onset could explain some of this discrepancy we investigated
      the relationship between two functional MTHFR gene polymorphisms and age at onset
      in this disorder. Scandinavian patients (n = 820) diagnosed with schizophrenia,
      schizoaffective disorder, and schizophreniform disorder were investigated. Two
      functional MTHFR single nucleotide polymorphisms (SNPs; rs1801131 and rs1801133)
      were genotyped and the effect of MTHFR polymorphisms on the age of onset was
      examined with survival analysis. In an attempt to replicate the findings from the
      Scandinavian sample, the association between rs1801133 and age at onset was also
      analyzed in Chinese high-risk families, with two or more affected siblings (n =
      243). Among the Scandinavian patients the functional MTHFR SNP rs1801133 (C677T)
      significantly affected age at onset of schizophrenia in a dose-dependent manner
      (P = 0.0015), with lower age of onset with increasing numbers of the mutant T
      allele. There was no evidence of rs1801131 (A1298C) affecting age of onset in
      schizophrenia. Within the Chinese high-risk families carriers of the MTHFR 677T
      allele showed earlier age at onset than siblings being homozygous for the wild
      type allele (P = 0.008). The MTHFR C677T polymorphism may play a role as a
      modifying factor for age of onset in schizophrenia.

PMID- 19746411
TI  - Re: Acknowledgement of human bioequivalency of matrix's lopinavir-ritonavir
      formulation to Kaletra, comment to article on Bioavailability of generic
      ritonavir and lopinavir/ritonavir tablet products in a dog model, by Garren et
      al.

PMID- 19746412
TI  - Absorption barriers in the rat intestinal mucosa: 1. Application of an in situ
      perfusion model to simultaneously assess drug permeation and metabolism.
AB  - Modulation of intestinal drug absorption barriers can have a profound impact on
      the bioavailability of orally administered compounds. With its commonality of use
      as an absorption model, it is valuable to assess the role of such barriers in the
      rat intestinal mucosa. In the present study, atenolol and verapamil were
      concomitantly delivered in the in situ perfused rat intestine in the presence or
      absence of inhibitors to simultaneously assess the function and modulation of
      passive diffusion barriers, cytochrome P450 (CYP)3A metabolism and P-glycoprotein
      (P-gp) efflux. A high performance liquid chromatography-tandem mass spectrometry
      method measured atenolol, verapamil and the CYP3A-mediated metabolite,
      norverapamil, with linearity (r(2) > 0.99), precision (CV <or=7.5%) and accuracy
      (+/-17%). Absorption of parent drug was independent of verapamil concentration;
      however the formation and disposition of norverapamil were concentration
      dependent and saturable. Norverapamil formation decreased (up to 80%) in the
      presence of CYP3A inhibitors and the fraction of norverapamil observed in the
      plasma was increased (4.5- to 7.2-fold) in the presence of P-gp inhibitors. These
      results suggest that in this model of the rat intestinal mucosa, atenolol serves
      as a marker for diffusion barriers whereas norverapamil formation and disposition
      are markers of CYP3A and P-gp, respectively.

PMID- 19746413
TI  - Use of flow cytometry as a quality control device for liquid-based cervical
      cytology specimens.
AB  - BACKGROUND: Cervical cancer is the second most common cancer in women worldwide
      comprising a major concern of public health. Liquid-based cytology provides
      significantly more effective detection of low-grade intraepithelial neoplasia or
      more severe lesions, without loss of diagnostic specificity and reduces the
      number of cases classified as unsatisfactory. The objective of the study is the
      evaluation of flow cytometry as a rapid tool for quality control of the liquid
      specimen adequacy for the purpose of precise cytological diagnosis in detecting
      cervical abnormalities. METHODS: A total of 1,854 women undergoing routine
      cervical cytology joined this cohort study. A monolayer smear was prepared and 1
      ml aliquot was removed and prepared for flow cytometric analysis. Cells were
      fixed and run on a Partec CyFlow SL, with front scatter (FSS) and side scatter
      (SSC) set on logarithmic scale. The forward scatter versus side scatter dot-plot
      was used for the distinction of ectocervical, endocervical, and polymorphonuclear
      cells. RESULTS: In the total of 1,854 cases, 15 specimens (0.8%) were
      characterized by the cytopathologist as unsatisfactory. Inadequacy was confirmed
      by flow cytometric analysis for four samples. Monolayer smears were reprepared
      for the remaining 11 samples. After the second microscopic observation, six out
      of the 11 cases (54.5%) were found to be satisfactory, whereas the remaining five
      were still designated as unsatisfactory by the cytopathologist. CONCLUSION: The
      parallel screening of adequacy by quantification of cell populations with flow
      cytometry can serve as an internal control for diagnosis and can overall decrease
      the number of unsatisfactory samples.

PMID- 19746414
TI  - Social learning, sexual and physical abuse, and adult crime.
AB  - This research examines the relationship between childhood physical and sexual
      abuse and the types of crimes committed by male adult offenders. We use the
      method of discriminant prediction to determine whether independent and dependent
      variables are related in ways that theories predict. Our analyses of data from
      the Survey of Inmates in State and Federal Correctional Facilities suggest that
      offenders model specific behaviors to which they have been exposed. Male
      offenders who were sexually abused as a child are more likely to commit sexual
      offenses, particularly sexual offenses against children, than nonsexual offenses.
      Offenders who were physically abused are more likely to engage in violent
      offenses than nonviolent offenses. Further analyses show that sexual offenders,
      and to a lesser extent violent offenders, are likely to specialize in those
      offenses. Our results are consistent with a social learning approach. They
      address a heretofore neglected issue: what exactly do children model when they
      are mistreated.

PMID- 19746415
TI  - Centriole symmetry: a big tale from small organisms.
AB  - Centrioles are microtubule-based cylindrical organelles with a 9-fold symmetry.
      They are essential for axoneme formation in cilia and flagella and for centrosome
      organization. In the basal hexapods Acerentomon microrhinus, we discovered
      unusually large centrioles composed of 14 doublet microtubules that serve as
      templates for cilia and flagella and organize mitotic and meiotic spindles. These
      observations challenge the long-standing view that centriole symmetry is highly
      conserved among eukaryotes. Strikingly, daughter centrioles contain a transient
      cartwheel that is lost after maturation. The length of radial spokes is like that
      found in 9-fold cartwheels, whereas the diameter of the hub varies according to
      the dimensions of the centriole cylinder. This suggests that the hub may dictate
      the master plan for centriole geometry. Finally, the finding that 14-doublet
      centrioles arise from 9-doublet mothers points to an alternative model for
      centriole assembly.

PMID- 19746416
TI  - Automated organelle-based colocalization in whole-cell imaging.
AB  - The use of fluorescence microscopy to investigate protein colocalization is an
      invaluable tool for understanding subcellular structures and their associated
      proteins. However, current techniques are largely limited to two-dimensional (2D)
      imaging and often require manual segmentation. Here, we present OBCOL, a
      methodology to automatically segment and quantify protein colocalization not
      within an image as a whole but on all individual punctuate organelles within a 3D
      multichannel image. A wide variety of colocalization statistics may then be
      calculated on the objects found, and features reported for each such as position,
      degree of overlap between channels, and number of component objects. OBCOL was
      validated on imaging of two fluorescent markers (Dextran, EGF) in 3D microscopy
      imaging. OBCOL's application was then exemplified by investigating the
      colocalization of three fluorescently tagged proteins (VAMP3, Rab11, and
      transferrin) on recycling endosomes in mammalian cells. The methodology showed
      for the first time the diversity of endosomes labeled with one or more of these
      proteins and quantitatively demonstrated the degree of overlap among these
      proteins in individual recycling endosomes. The consistent segregation of these
      markers provides novel evidence for the subcompartmentalization of recycling
      endosomes. OBCOL is a flexible methodology for 3D multifluorophore image
      analysis. This study clearly demonstrated its value for investigating subcellular
      structures and their constituent proteins.

PMID- 19746417
TI  - Automated multichannel fluorescent whole slide imaging and its application for
      cytometry.
AB  - Slide-based image cytometry (SBC) has several advantages over flow cytometry but
      it is not widely used because of its low throughput, complicated workflow, and
      high price. Fully automated microscopes became affordable with the advent of
      whole slide imaging (WSI) and they can be transformed into a cytometer. A MIRAX
      MIDI automated whole slide imager was used with metal-halide and light emitting
      diode (LED)-based fluorescent illumination, filter block changer, and a cooled
      monochrome charge coupled device camera. The MIRAX control software was further
      developed for fluorescent sample detection, autofocusing, multichannel
      digitization, and signal correction due to nonuniform illumination. Fluorescent
      calibration beads were used to verify the linearity of the system. The HistoQuant
      software package of the MIRAX viewer was used for image segmentation and
      quantitative analysis. The data was displayed by the histogram, scatter plot, and
      gallery functions of the same program. Fluorescent samples can be reliably
      detected, focused, and scanned. The measured integrated fluorescence showed
      linearity with exposure time and staining intensity. Automated fluorescent WSI
      with stable LED illumination and high-quality homogeneous fluorescent slides can
      be used conveniently for SBC.

PMID- 19746418
TI  - Generation of a human immunodeficiency virus type 1 chronically infected monkey B
      cell line expressing low levels of endogenous TRIM5alpha.
AB  - Several innate cellular antiviral factors exist in mammalian cells that prevent
      the replication of retroviruses. Among them, the tripartite motif protein
      (TRIM)5alpha has been shown to block human immunodeficiency virus type 1 (HIV-1)
      infection in several types of Old World monkey cells. Here we report a novel HIV
      1 chronically infected monkey B cell line, F6/HIV-1, characterized by very low
      levels of TRIM5alpha expression that allows HIV-1 to overcome the restriction.
      Virus produced by F6/HIV-1 cells fails to infect monkey cells but retains the
      ability to infect human peripheral blood mononuclear cells (PBMCs) and T cell
      lines, although with a reduced infectivity compared to the input virus.
      Ultrastructural analyses revealed the presence of budding virions at the F6/HIV-1
      cells plasma membrane characterized by a typical conical core shell. To our
      knowledge F6/HIV-1 is the first monkey cell line chronically infected by HIV-1
      and able to release infectious particles thus representing a useful tool to gain
      further insights into the molecular mechanisms of HIV-1 pathogenesis.

PMID- 19746419
TI  - Polyamine effects on cell function: Possible central role of plasma membrane
      PI(4,5)P2.
AB  - The polyamines spermidine, spermine, and putrescine are intimately involved in
      and required for cell growth and proliferation. There are also multiple effects
      of polyamines on other cellular processes that seem not to be a result of changes
      in protein expression. It is a daunting task to classify and understand cellular
      effects of endogenous polyamines. There has been no central hypothesis how these
      effects can occur or how spermine and spermidine could be targeted to various
      signal transduction cascades. However, now there is evidence that multiple
      effects of endogenous polyamines on different cellular processes may involve
      plasma membrane PI(4,5)P(2) and recent evidence of how polyamines could be
      targeted to specific cellular functions.

PMID- 19746420
TI  - Induction of Th17 differentiation by corneal epithelial-derived cytokines.
AB  - This study was to explore a potential role of epithelium-derived cytokines in
      Th17 differentiation. Th17 induction was evaluated by murine CD4(+) T cells
      treated with different combinations of five inducing cytokines, or conditioned
      media of human corneal epithelial cells (HCECs) exposed to a variety of stimuli.
      Th17 differentiation was determined by measuring Th17 associated molecules, IL
      17A, IL-17F, IL-22, CCL-20, and STAT3 at mRNA and protein levels, and numbers of
      IL-17-producing T cells by real-time PCR, and cytokine immunobead and ELISPOT
      assays, respectively. IL-23 was the strongest inducer for expanding Th17 cells in
      the presence of TGF-beta1 + IL-6; and IL-1beta was the strongest Th17 amplifier
      in the presence of TGF-beta1 + IL-6 + IL-23. These inducing cytokines were found
      to be significantly stimulated in HCECs challenged by hyperosmotic media (450
      mOsM), microbial components (polyI:C, flagellin, R837, and other TLR ligands) and
      TNF-alpha. Interestingly, when incubated with conditioned media of HCECs
      irritated by polyI:C or TNF-alpha, CD4(+) T cells displayed increased mRNA levels
      of IL-17A, IL-17F, IL-22, CCL-20, and STAT3, increased IL-17 protein in the
      supernatant, and increased numbers of IL-17-producing T cells (Th17 cells). These
      findings demonstrate for the first time that Th17 differentiation can be promoted
      by cytokines produced by corneal epithelium that are exposed to hyperosmotic,
      microbial, and inflammatory stimuli.

PMID- 19746421
TI  - ROCK pathway participates in the processes that 15-hydroxyeicosatetraenoic acid
      (15-HETE) mediated the pulmonary vascular remodeling induced by hypoxia in rat.
AB  - 15-Hydroxyeicosatetraenoic acid (15-HETE), a product of arachidonic acid (AA)
      catalyzed by 15-lipoxygenase (15-LO), plays an essential role in hypoxic
      pulmonary arterial hypertension. We have previously shown that 15-HETE inhibits
      apoptosis in pulmonary artery smooth muscle cells (PASMCs). To test the
      hypothesis that such an effect is attributable to the hypoxia-induced pulmonary
      vascular remodeling (PVR), we performed these studies. We found subtle thickening
      of proximal media/adventitia of the pulmonary arteries (PA) in rats that had been
      exposed to hypoxia. This was associated with an up-regulation of the anti
      apoptotic Bcl-2 expression and down-regulation of pro-apoptotic caspase-3 and Bax
      expression in PA homogenates. Nordihydroguaiaretic acid (NDGA), which inhibits
      the generation of endogenous 15-HETE, reversed all the alterations following
      hypoxia. In situ hybridization histochemistry and immunocytochemistry showed that
      the 15-LO-1 mRNA and protein were localized in pulmonary artery endothelial cells
      (PAECs), while the 15-LO-2 mRNA and protein were localized in both PAECs and
      PASMCs. Furthermore, the Rho-kinase (ROCK) pathway was activated by both
      endogenous and exogenous 15-HETE, alleviating the serum deprivation (SD)-induced
      PASMC apoptosis. Thus, these findings indicate that 15-HETE protects PASMC from
      apoptosis, contributing to pulmonary vascular medial thickening, and the effect
      is, at least in part, mediated via the ROCK pathway.

PMID- 19746422
TI  - Features of sequential learning in hemicerebellectomized rats.
AB  - Because the sequencing property is one of the functions in which cerebellar
      circuits are involved, it is important to analyze the features of sequential
      learning in the presence of cerebellar damage. Hemicerebellectomized and control
      rats were tested in a four-choice visuomotor learning task that required both the
      detection of a specific sequence of correct choices and the acquisition of
      procedural rules about how to perform the task. The findings indicate that the
      presence of the hemicerebellectomy did not affect the first phases of detection
      and acquisition of the sequential visuomotor task, delayed but did not prevent
      the learning of the sequential task, slowed down speed-up and proceduralization
      phases, and loosened the reward-response associative structure. The performances
      of hemicerebellectomized animals in the serial learning task as well as in the
      open field task demonstrated that the delayed sequential learning task could not
      be ascribed to impairment of motor functions or discriminative abilities or to
      low levels of motivation. The delay in sequential learning observed in the
      presence of a cerebellar lesion appeared to be related mainly to a delay of the
      automatization of the response. In conclusion, it may be advanced that, through
      cortical and subcortical connections, the cerebellum provides the acquisition of
      rapid and accurate sensory-guided sequence of responses.

PMID- 19746423
TI  - Effects of the flavonoid casticin from Brazilian Croton betulaster in cerebral
      cortical progenitors in vitro: direct and indirect action through astrocytes.
AB  - Neurodegenerative diseases are a major constraint on the social and economic
      development of many countries. Evidence has suggested that phytochemicals have an
      impact on brain pathology; however, both their mechanisms of action and their
      cell targets are incompletely known. Here, we investigated the effects of the
      flavonoid casticin, extracted from Croton betulaster, a common plant in the state
      of Bahia in Brazil, on rat cerebral cortex neurons in vitro. Treatment of neural
      progenitors with 10 microM casticin increased the neuronal population positive
      for the neuronal marker beta-tubulin III and the neuronal transcriptional factor
      Tbr2 by approximately 20%. This event was followed by a 50% decrease in neuronal
      death. Pools of astrocyte (GFAP and S100beta), neural (nestin), and
      oligodendrocyte (Olig2 and NG2) progenitors were not affected by casticin.
      Neither neuronal commitment nor proliferation of progenitors was affected by
      casticin, suggesting a neuroprotective effect of this compound. Culture of neural
      progenitors on casticin-treated astrocyte monolayers increased the neuronal
      population by 40%. This effect was reproduced by conditioned medium derived from
      casticin-treated astrocytes, suggesting the involvement of a soluble factor.
      ELISA assays of the conditioned medium revealed a 20% increase in interleukin-6
      level in response to casticin. In contrast to the direct effect, neuronal death
      was unaffected, but a 52% decrease in the death of nestin-positive progenitors
      was observed. Together our data suggest that casticin influences the neuronal
      population by two mechanisms: 1) directly, by decreasing neuronal death, and 2)
      indirectly, via astrocytes, by modulating the pool of neuronal progenitors.

PMID- 19746424
TI  - Cuprizone induces similar demyelination in male and female C57BL/6 mice and
      results in disruption of the estrous cycle.
AB  - Multiple sclerosis is a demyelinating neurological disease that is influenced by
      gender, primarily reflected in greater susceptibility to disease development in
      women than in men. Cuprizone intoxication, an animal model that is used to study
      demyelination and remyelination, has been extensively characterized in male
      C57BL/6 mice. Here, we have undertaken a comprehensive characterization of the
      morphological and cellular processes that occur in female C57BL/6J mice during
      cuprizone-induced demyelination and subsequent remyelination and compared them
      with age-matched male mice. We find that the pattern of demyelination and
      remyelination is similar between genders and that there is little or no
      difference in the loss or repopulation of mature oligodendrocytes or accumulation
      of reactive glia. Furthermore, examination of alphaERKO and betaERKO mice
      suggests that estrogen receptors do not affect the outcome for demyelination or
      remyelination. Interestingly, we found that cuprizone treatment disrupts estrous
      cyclicity in female mice, possibly interfering with potential hormone influences
      on demyelination and remyelination. Therefore, cuprizone-induced demyelination in
      C57BL/6J mice may have limitations as a model for the study of sex differences.

PMID- 19746425
TI  - K(ATP) channel openers protect mesencephalic neurons against MPP+-induced
      cytotoxicity via inhibition of ROS production.
AB  - Opening of ATP-sensitive potassium (K(ATP)) channels has been demonstrated to
      exert significant neuroprotection in in vivo and in vitro models of Parkinson's
      disease (PD), but the exact mechanism remains unclear. In the present study,
      various K(ATP) channel openers (KCOs) sensitive to diverse K(ATP) subunits were
      used to clarify the protective role of K(ATP) channel opening in 1-methyl-4
      phenylpyridinium (MPP(+))-induced oxidative stress injury in mouse primary
      cultured mesencephalic neurons. The results showed that pretreatment with
      nonselective KCO pinacidil (Pin) or diazoxide (Dia), a KCO sensitive to
      Kir6.2/SUR1 K(ATP) channels, protected mesencephalic neurons, especially
      dopaminergic neurons, against MPP(+)-induced injury in a concentration-dependent
      manner. However, cromakalim (Cro), an opener of Kir6.1/SUR2 but not Kir6.2/SUR1
      K(ATP) channels, failed to protect against MPP(+)-induced cytotoxicity.
      Furthermore, Pin and Dia but not Cro significantly suppressed the elevation of
      reactive oxygen species (ROS) triggered by MPP(+) and prevented the loss of
      mitochondrial member potential (Delta Psi m) and the release of mitochondrial
      cytochrome c. Consequently, opening of K(ATP) channels expressed in neurons could
      protect primary mesencephalic neurons against MPP(+)-induced cytotoxicity via
      inhibiting ROS overproduction and subsequently ameliorating mitochondrial
      function.

PMID- 19746426
TI  - Uptake of ferrous iron by cultured rat astrocytes.
AB  - Astrocytes are considered to play an important role in iron homeostasis of the
      brain, yet the mechanisms involved in the uptake of iron into astrocytes remain
      elusive. To investigate the uptake of iron into astrocytes, we have applied
      ferric ammonium citrate (FAC) to rat astrocyte-rich primary cultures. These
      cultures express the mRNAs of two membrane-bound ferric reductases, Dcytb and
      SDR2, and reduce extracellular ferric iron (100 muM) with a rate of 3.2 +/- 0.4
      nmol/(hr x mg). This reduction rate is substantially lower than the rate of
      cellular iron accumulation from 100 muM FAC [24.7 +/- 8.9 nmol/(hr x mg)], which
      suggests that iron accumulation from FAC does at best partially depend on
      extracellular ferric reduction. Nonetheless, when the iron in FAC was almost
      completely reduced by an excess of exogenous ascorbate, astrocytes accumulated
      iron in a time- and concentration-dependent manner with specific iron
      accumulation rates that increased linearly for concentrations of up to 100 muM
      ferrous iron. This accumulation was attenuated by lowering the incubation
      temperature, by the presence of ferrous iron chelators, or by lowering the pH
      from 7.4 to 6.8. These data indicate that, in addition to the DMT1-mediated
      uptake of ferrous iron, astrocytes can accumulate ferric and ferrous iron by
      mechanisms that are independent of DMT1 or transferrin.

PMID- 19746427
TI  - Altered AMPA receptor expression with treadmill exercise in the 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine-lesioned mouse model of basal ganglia injury.
AB  - Dopamine depletion leads to impaired motor performance and increased
      glutamatergic-mediated hyperexcitability of medium spiny neurons in the basal
      ganglia. Intensive treadmill exercise improves motor performance in both saline
      treatment and the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model
      of Parkinson's disease. In the present study, we investigated the effect of high
      intensity treadmill exercise on changes in alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid receptor (AMPAR) subunit expression, because these
      receptor channels confer the majority of fast excitatory neurotransmission in the
      brain, and their subunit composition provides a key mechanism for regulating
      synaptic strength and synaptic neuroplasticity and is important in modulating
      glutamatergic neurotransmission. Within the dorsolateral striatum of MPTP mice,
      treadmill exercise increased GluR2 subunit expression, with no significant effect
      on GluR1. Furthermore, neurophysiological studies demonstrated a reduction in the
      size of excitatory postsynaptic currents (EPSCs) in striatal medium spiny neurons
      (as determined by the input-output relationship), reduced amplitude of
      spontaneous EPSCs, and a loss of polyamine-sensitive inward rectification, all
      supportive of an increase in heteromeric AMPAR channels containing the GluR2
      subunit. Phosphorylation of GluR2 at serine 880 in both saline-treated and MPTP
      mice suggests that exercise may also influence AMPAR trafficking and thus
      synaptic strength within the striatum. Finally, treadmill exercise also altered
      flip isoforms of GluR2 and GluR1 mRNA transcripts. These findings suggest a role
      for AMPARs in mediating the beneficial effects of exercise and support the idea
      that adaptive changes in GluR2 subunit expression may be important in modulating
      experience-dependent neuroplasticity of the injured basal ganglia.

PMID- 19746428
TI  - Immune activation or immunomodulation in the brains of MPS IIIB mice? Commentary
      on "Innate and adaptive immune activation in the brain of MPS IIIB mouse model".

PMID- 19746429
TI  - Randomized controlled trial: Comparative efficacy for the treatment of facial
      telangiectasias with 532 nm versus 940 nm diode laser.
AB  - BACKGROUND: While the 532 nm wavelength has been demonstrated to be effective for
      facial telangiectasias, 940 nm is a novel wavelength which has only been reported
      in case reports. While both the 532 and 940 nm wavelengths are effective for
      facial telangiectasias, we lack evidence to support whether one wavelength is
      superior. STUDY DESIGN: Randomized, blinded split-faced trial for the 532 and 940
      nm diode laser wavelengths. Side effects of erythema, crusting, swelling, and
      blistering (0-5 scale, 0 = not present, 1 = trace, 5 = severe) were assessed.
      Prior to treatment and at 2 months after a series of two treatments,
      telangiectasias were assessed (1-10 scale, 1 = focal telangiectasias, 10 =
      diffuse telangiectasias). Assessment of the degree of improvement in facial
      telangiectasias was performed by two blinded non-treating physician evaluators
      from patient photographs. RESULTS: A total of 24 facial anatomic sites were
      treated with the 532 and 940 nm wavelengths. Presence and severity of side
      effects of erythema, crusting, swelling, blistering (0-5 scale, 0 = not present,
      1 = trace, 5 = severe) were assessed. Pain associated with the laser treatment
      was rated as significantly less for the 940 nm wavelength relative to the 532 nm
      wavelength. Erythema post-treatment was significantly less with 940 nm relative
      to 532 nm. Significant crusting and swelling were only reported with the 532 nm
      wavelength. The mean percentage improvement with the 940 nm wavelength (63.0%)
      was greater than that achieved with the 532 nm wavelength (47.8%) (P<0.05). On
      photographic evaluation, 940 nm was significantly more efficacious for larger
      caliber vessels than 532 nm. Both wavelengths were equally efficacious for
      smaller caliber vessels. CONCLUSIONS: While both 532 and 940 nm diode laser
      produced significant improvement in facial telangiectasias, greater efficacy was
      found with 940 nm as well as a significantly more tolerable side effect profile.
      Lasers Surg. Med. 41:555-562, 2009. (c) 2009 Wiley-Liss, Inc.

PMID- 19746430
TI  - Deep thiopental anesthesia alters steady-state glucose homeostasis but not the
      neurochemical profile of rat cortex.
AB  - Barbiturates are regularly used as an anesthetic for animal experimentation and
      clinical procedures and are frequently provided with solubilizing compounds, such
      as ethanol and propylene glycol, which have been reported to affect brain
      function and, in the case of (1)H NMR experiments, originate undesired resonances
      in spectra affecting the quantification. As an alternative, thiopental can be
      administrated without any solubilizing agents. The aim of the study was to
      investigate the effect of deep thiopental anesthesia on the neurochemical profile
      consisting of 19 metabolites and on glucose transport kinetics in vivo in rat
      cortex compared with alpha-chloralose using localized (1)H NMR spectroscopy.
      Thiopental was devoid of effects on the neurochemical profile, except for the
      elevated glucose at a given plasma glucose level resulting from thiopental
      induced depression of glucose consumption at isoelectrical condition. Over the
      entire range of plasma glucose levels, steady-state glucose concentrations were
      increased on average by 48% +/- 8%, implying that an effect of deep thiopental
      anesthesia on the transport rate relative to cerebral glucose consumption ratio
      was increased by 47% +/- 8% compared with light alpha-chloralose-anesthetized
      rats. We conclude that the thiopental-induced isoelectrical condition in rat
      cortex significantly affected glucose contents by depressing brain metabolism,
      which remained substantial at isoelectricity.

PMID- 19746431
TI  - Activation of nuclear factor kappa B in mammary epithelium promotes milk loss
      during mammary development and infection.
AB  - We investigated whether nuclear factor kappa B (NF-kappaB), which exhibits a
      regulated pattern of activity during murine mammary gland development, plays an
      important role during lactation and involution, when milk production ceases and
      the gland undergoes apoptosis and re-modeling. We generated a doxycycline
      inducible transgenic mouse model to activate NF-kappaB specifically in the
      mammary epithelium through expression of a constitutively active form of IKK2,
      the upstream kinase in the classical NF-kappaB signaling cascade. We found that
      activation of NF-kappaB during involution resulted in a more rapid reduction in
      milk levels and increased cleavage of caspase-3, an indicator of apoptosis. We
      also found that activation of NF-kappaB during lactation with no additional
      involution signals had a similar effect. The observation that NF-kappaB is a key
      regulator of milk production led us to investigate the role of NF-kappaB during
      mastitis, an infection of the mammary gland in which milk loss is observed.
      Mammary gland injection of E. coli LPS resulted in activation of NF-kappaB and
      milk loss during lactation. This milk loss was decreased by selective inhibition
      of NF-kappaB in mammary epithelium. Together, our data reveal that activation of
      NF-kappaB leads to milk clearance in the lactating mammary gland. Therefore,
      targeting of NF-kappaB signaling may prove therapeutic during mastitis in humans
      and could be beneficial for the dairy industry, where such infections have a
      major economic impact.

PMID- 19746432
TI  - Pulsed dye laser-induced inflammatory response and extracellular matrix turnover
      in rat vocal folds and vocal fold fibroblasts.
AB  - BACKGROUND AND OBJECTIVES: Disruption of the vocal fold extracellular matrix
      (ECM) can induce a profound and refractory dysphonia. Pulsed dye laser (PDL)
      irradiation has shown early promise as a treatment modality for disordered ECM in
      patients with chronic vocal fold scar; however, there are limited data addressing
      the mechanism by which this laser energy might induce cellular and extracellular
      changes in vocal fold tissues. In this study, we examined the inflammatory and
      ECM modulating effects of PDL irradiation on normal vocal fold tissues and
      cultured vocal fold fibroblasts (VFFs). STUDY DESIGN/MATERIALS AND METHODS: We
      evaluated the effects of 585 nm PDL irradiation on inflammatory cytokine and
      collagen/collagenase gene transcription in normal rat vocal folds in vivo (3-168
      hours following delivery of approximately 39.46 J/cm(2) fluence) and VFFs in
      vitro (3-72 hours following delivery of 4.82 or 9.64 J/cm(2) fluence). We also
      examined morphological vocal fold tissue changes 3 hours, 1 week, and 1 month
      post-irradiation. RESULTS: PDL irradiation altered inflammatory cytokine and
      procollagen/collagenase expression at the transcript level, both in vitro and in
      vivo. Additionally, PDL irradiation induced an inflammatory repair process in
      vivo that was completed by 1 month with preservation of normal tissue morphology.
      CONCLUSIONS: PDL irradiation can modulate ECM turnover in phenotypically normal
      vocal folds. Additional work is required to determine if these findings extend to
      disordered ECM, such as is seen in vocal fold scar. Lasers Surg. Med. 41:585-594,
      2009. (c) 2009 Wiley-Liss, Inc.

PMID- 19746433
TI  - "Juvenile stress" alters maturation-related changes in expression of the neural
      cell adhesion molecule L1 in the limbic system: relevance for stress-related
      psychopathologies.
AB  - L1 is critically involved in neural development and maturation, activity
      dependent synaptic plasticity, and learning processes. Among adult rats, chronic
      stress protocols that affect L1 functioning also induce impaired cognitive and
      neural functioning and heightened anxiety reminiscent of stress-induced mood and
      anxiety disorders. Epidemiological studies indicate that childhood trauma is
      related predominantly to higher rates of both mood and anxiety disorders in
      adulthood and is associated with altered limbic system functioning. Exposing rats
      to stress during the juvenile period ("juvenile stress") has comparable effects
      and was suggested as a model of induced predisposition for these disorders. This
      study examined the effects of juvenile stress on rats aversive learning and on L1
      expression soon after exposure and in adulthood, both following additional
      exposure to acute stress and in its absence. Adult juvenile-stressed rats
      exhibited enhanced cued fear conditioning, reduced novel-setting exploration, and
      impaired avoidance learning. Furthermore, juvenile stress increased L1 expression
      in the BLA, CA1, DG, and EC both soon after the stressful experience and during
      adulthood. It appears that juvenile stress affects the normative maturational
      decrease in L1 expression. The results support previous indications that juvenile
      stress alters the maturation of the limbic system and further support a role for
      L1 regulation in the mechanisms that underlie the predisposition to exhibit mood
      and/or anxiety disorders in adulthood. Furthermore, the findings support the
      "network hypothesis," which postulates that information-processing problems
      within relevant neural networks might underlie stress-induced mood and anxiety
      disorders.

PMID- 19746434
TI  - Immediate anti-tumor necrosis factor-alpha (etanercept) therapy enhances axonal
      regeneration after sciatic nerve crush.
AB  - Peripheral nerve regeneration begins immediately after injury. Understanding the
      mechanisms by which early modulators of axonal degeneration regulate neurite
      outgrowth may affect the development of new strategies to promote nerve repair.
      Tumor necrosis factor-alpha (TNF-alpha) plays a crucial role in the initiation of
      degenerative cascades after peripheral nerve injury. Here we demonstrate using
      real-time Taqman quantitative RT-PCR that, during the time course (days 1-60) of
      sciatic nerve crush, TNF-alpha mRNA expression is induced at 1 day and returned
      to baseline at 5 days after injury in nerve and the corresponding dorsal root
      ganglia (DRG). Immediate therapy with the TNF-alpha antagonist etanercept (fusion
      protein of TNFRII and human IgG), administered systemically (i.p.) and locally
      (epineurially) after nerve crush injury, enhanced the rate of axonal
      regeneration, as determined by nerve pinch test and increased number of
      characteristic clusters of regenerating nerve fibers distal to nerve crush
      segments. These fibers were immunoreactive for growth associated protein-43 (GAP
      43) and etanercept, detected by anti-human IgG immunofluorescence. Increased GAP
      43 expression was found in the injured nerve and in the corresponding DRG and
      ventral spinal cord after systemic etanercept compared with vehicle treatments.
      This study established that immediate therapy with TNF-alpha antagonist supports
      axonal regeneration after peripheral nerve injury.

PMID- 19746435
TI  - Survival, differentiation, and reversal of heroin neurobehavioral teratogenicity
      in mice by transplanted neural stem cells derived from embryonic stem cells.
AB  - Cell therapies in animal models of neurobehavioral defects are normally derived
      from neural stem cells (NSC) of the developing cortex. However, the clinical
      feasibility of NSC therapies would be greatly improved by deriving transplanted
      cells and from a tissue culture source that is self-renewing, containing cells
      that potentially differentiate into the desired neuronal phenotypes. These
      cultures can be engineered to contain the appropriate factors to support their
      therapeutic action and likely evoke lesser immune reactions. In the current
      study, we employed our model of mice neurobehaviorally impaired via prenatal
      exposure to heroin, to test the therapeutic efficacy of NSC derived from murine
      embryonic stem cells culture (ESC). The culture contained elongated bipolar
      cells, 90% of which are positive for nestin, the intermediate filament protein
      found in neural precursors. After removal of growth factors, the NSC
      differentiated into neurons (34.0% +/- 3.8% NF-160 positive), including
      cholinergic cells (ChAT positive), oligodendrocytes (29.9% +/- 4.2% O(4)), and
      astrocytes (36.1% +/- 4.7% GFAP positive). Reverse transcriptase polymerase chain
      reaction (RT-PCR) analysis confirmed the immunocytochemical findings. Mice made
      deficient in Morris maze behavior by prenatal heroin exposure (10 mg/kg heroin
      s.c. on gestational days 9-18) were transplanted into the hippocampus region on
      postnatal day 35 with the ES culture-derived NSC (ES-NSC) labeled with
      dialkylcarbocyanine (Dil) cell tracker. Dil+ and NF160+ cells were detected in
      the hippocampal region (50% +/- 8% survival). The transplantation completely
      restored maze performance to normal; e.g., on day 3, transplantation improved the
      behavior from the deficient level of 11.9-sec latency to the control of 5.6-sec
      latency (44.5% improvement).

PMID- 19746436
TI  - Expression of RIZ1 protein (Retinoblastoma-interacting zinc-finger protein 1) in
      prostate cancer epithelial cells changes with cancer grade progression and is
      modulated in vitro by DHT and E2.
AB  - The nuclear protein methyl-transferase Retinoblastoma-interacting zinc-finger
      protein 1 (RIZ1) is considered to be a downstream effector of estrogen action in
      target tissues. Silencing of RIZ1 expression is common in many tumors. We
      analyzed RIZ1 expression in normal and malignant prostate tissue and evaluated
      whether estradiol (E2) or dihydrotestosterone (DHT) treatment modulated RIZ1 in
      cultured prostate epithelial cells (PEC). Moreover, we studied the possible
      involvement of RIZ1 in estrogen action on the EPN prostate cell line,
      constitutively expressing both estrogen receptor (ER)-alpha and beta. RIZ1
      protein, found in the nucleus of normal PECs by immunohistochemistry, was
      progressively lost in cancer tissues as the Gleason score increased and was only
      detected in the cytoplasmic compartment. RIZ1 transcript levels, as assayed by
      semi-quantitative RT-PCR in primary PEC cultures, were significantly reduced in
      cancer cells (P < 0.05). In EPN DHT treatment significantly increased RIZ1
      transcript and protein levels (P < 0.05); E2 induced a reduction of S phase
      without significant changes of RIZ1 expression. In E2-treated EPN cell extracts
      RIZ co-immunoprecipitated with ERbeta and ERalpha. Our data demonstrate that RIZ1
      is expressed in normal PECs and down-regulated in cancer cells, with a switch of
      its sub-cellular localization from the nucleus to the cytoplasm upon cancer grade
      progression. RIZ1 expression levels in the PECs were modulated by DHT or E2
      treatment in vitro. Furthermore, the E2 effects on ER-expressing prostate cells
      involve RIZ1, which confirms a possible role for ER-mediated pathways in a non
      classic E(2)-target tissue.

PMID- 19746437
TI  - Vitamin D deficiency in young children with severe acute lower respiratory
      infection.
AB  - RATIONALE: Acute lower respiratory infection (ALRI) is one of the most common
      reasons for hospitalization and intensive care unit admission among children.
      Season related decreases in the immunomodulatory molecule, vitamin D, remain an
      unexplored factor that might contribute to the increased occurrence of ALRI in
      children. OBJECTIVE: To investigate a possible association between vitamin D
      deficiency and respiratory infection by comparing serum 25 hydroxyvitamin D
      [25(OH)D] levels in a group of young children with ALRI to an age-matched group
      without respiratory infection. PATIENTS AND METHODS: Participants with a
      diagnosis of bronchiolitis or pneumonia (n = 55 or 50, respectively), as well as
      control subjects without respiratory symptoms (n = 92), were recruited at the
      Royal University Hospital, Saskatoon, Saskatchewan, Canada from November 2007 to
      May 2008. 25(OH)D levels were measured in patient serum using a competitive
      enzyme linked immunoassay. RESULTS: The mean vitamin D level for the entire ALRI
      group was not significantly different from the control group (81 +/- 40 vs. 83 +/
      30 nmol/L, respectively). The mean vitamin D level for the ALRI subjects
      admitted to the pediatric intensive care unit (49 +/- 24 nmol/L) was
      significantly lower than that observed for both control (83 +/- 30 nmol/L) and
      ALRI subjects admitted to the general pediatrics ward (87 +/- 39 nmol/L). Vitamin
      D deficiency remained statistically related to pediatric intensive care unit
      admission in the multivariate analysis. CONCLUSION: No difference was observed in
      vitamin D levels between the entire ALRI group and control groups; however,
      significantly more children admitted to the pediatric intensive care unit with
      ALRI were vitamin D deficient. These findings suggest that the immunomodulatory
      properties of vitamin D might influence ALRI disease severity.

PMID- 19746438
TI  - Therapeutic bronchoscopy in a child with sand aspiration and respiratory failure
      from near drowning--case report and literature review.
AB  - Foreign matter aspiration occurs relatively commonly in drowning and near
      drowning events. In most cases, stomach contents are aspirated. Sand aspiration
      rarely occurs and there are no reported cases in children with near drowning.
      Limited data are available on clinical presentation and management of sand
      aspiration with accidental burial. We report a 3-year-old boy who nearly drowned
      while swimming in brackish waters and was found face down in sand. Sand
      aspiration was suspected when the child continued to have persistent wheezing and
      high ventilatory requirement despite intensive bronchodilator and corticosteroids
      therapy with an inability to wean after 4 days post-near-drowning event.
      Radiology was non-specific in the absence of sand bronchogram. Presence of sand
      in the airways was confirmed when a bronchoscopy was undertaken and sand seen in
      the bronchoalveolar lavage fluid. Sequential lung washing followed by exogenous
      surfactant administration (3 ml/kg) was undertaken and lead to significant
      improvement such that within 12 hr post-therapeutic lavage, his ventilatory
      requirements reduced substantially. The child was extubated 4 days post-lavage
      and on review 2 months post-event, was clinically well with airway resistance
      within normal predicted values measured on forced oscillatory spirometry (IOS).

PMID- 19746439
TI  - Leukotriene receptor antagonist in the treatment of childhood allergic rhinitis-
      a randomized placebo-controlled study.
AB  - OBJECTIVE: This study was designed to assess the hypothesis that leukotriene
      receptor antagonists (LTRAs) would provide additional symptom relief in asthmatic
      children with persistent AR already taking regular antihistamine. The effects of
      16-week treatment of LTRA in addition to fexofenadine (FEX) on persistent AR in
      asthmatic children were examined. STUDY DESIGN: Consecutive children with stable
      asthma and persistent AR were invited in this randomized, double-blind, placebo
      controlled study. After a 2-week run-in period in which subjects were given FEX
      alone, they were randomly assigned to take LTRA or placebo in addition to FEX for
      16 weeks, followed by 8 weeks of follow-up phase with FEX taken alone. Symptom
      scoring, rhinoscopy, acoustic rhinometry, spirometry, nasal secretion extraction
      and blood taking for IL-4 and IL-13 analysis were performed after a 2-week run-in
      and at the end of treatment. RESULTS: Forty-four subjects with a median (IQR) age
      of 12.2 (10.1-14.1) years were recruited. At week 4 of treatment, the between
      group differences in the mean changes of daytime sneezing score (mean difference
      (95% CI) = -0.35 (-0.59, -0.12), P = 0.004), nighttime sneezing score (mean
      difference (95% CI) = -0.37 (-0.62, -0.11), P = 0.007) and daytime composite
      score (mean difference (95% CI) = -1.08 (-1.92, -0.25), P = 0.013) were
      significant. Acoustic rhinometry also demonstrated a nearly significant
      difference in nasal volume change between groups at 16 weeks of treatment (mean
      difference (95% CI) = 0.572 (0.090-1.054), P = 0.021). IL-4 and IL-13 were not
      detected in the majority of nasal secretion or serum samples. CONCLUSIONS:
      Additional LTRA provided a more rapid relief on sneezing at the 4-week time
      point. This combination therapy also maintained a greater nasal volume and this
      might translate to lesser nasal congestion.

PMID- 19746440
TI  - Computational approaches to identifying and characterizing protein binding sites
      for ligand design.
AB  - Given the three-dimensional structure of a protein, how can one find the sites
      where other molecules might bind to it? Do these sites have the properties
      necessary for high affinity binding? Is this protein a suitable target for drug
      design? Here, we discuss recent developments in computational methods to address
      these and related questions. Geometric methods to identify pockets on protein
      surfaces have been developed over many years but, with new algorithms, their
      performance is still improving. Simulation methods show promise in accounting for
      protein conformational variability to identify transient pockets but lack the
      ease of use of many of the (rigid) shape-based tools. Sequence and structure
      comparison approaches are benefiting from the constantly increasing size of
      sequence and structure databases. Energetic methods can aid identification and
      characterization of binding pockets, and have undergone recent improvements in
      the treatment of solvation and hydrophobicity. The "druggability" of a binding
      site is still difficult to predict with an automated procedure. The methodologies
      available for this purpose range from simple shape and hydrophobicity scores to
      computationally demanding free energy simulations.

PMID- 19746441
TI  - When a man hits a woman: moral evaluations and reporting violence to the police.
AB  - We use experimental data from a nationally representative sample to examine
      whether gender and the victim's relationship to the offender affect attitudes
      about the seriousness of the offense and whether the offense should be reported
      to the police. We find that respondents are particularly likely to condemn men's
      assaults on women, and to favor reporting them. The pattern appears to reflect
      both greater moral condemnation of men's assaults on women and the belief that
      the victims of these assaults are in greater danger. In general, moral judgments
      and attitudes toward reporting do not depend on the gender, age, level of
      education, or political ideology of the respondent. Condemnation of men's
      violence against women, and support for police intervention when it occurs, are
      apparently widespread across different segments of the population.

PMID- 19746442
TI  - The ischial callosities of Sulawesi macaques.
AB  - Sulawesi island has a high level of endemism, including the seven species of
      monkey from the genus Macaca (macaques). These monkeys have a pair of sitting
      pads, termed ischial callosities that have diverse shapes and previously were
      described verbally only. Although useful, these verbal descriptions cannot fully
      describe shape variation and are somewhat subjective, and cannot directly be used
      to analyze relationships among species. Here, we report a quantitative analysis
      of shape of Sulawesi macaque ischial callosities using geometric morphometric
      tools to optimally describe shape variation and objectively reconstruct general
      pattern of callosity shapes. By quantification of shape variation, we compare the
      relationships of each Sulawesi macaque species with each other and with the two
      geographically neighboring macaque species, M. nemestrina and M. fascicularis, by
      consensus coordinates of the callosity outlines. The Sulawesi macaques have a
      wider degree of variation compared with M. fascicularis and M. nemestrina;
      variation exists in the dorsal part and in the bending of the callosity. There
      are three general types of callosity shape in Sulawesi macaques: oval without
      bending (M. tonkeana and M. maurus), oval with outward bending (M. ochreata and
      M. brunnescens), and oval or reniform with inward bending (M. hecki, M.
      nigrescens, and M. nigra). These types are congruent with their geographical
      distribution. The pathway of shape change may have started from oval without
      bending in the center and the southern peninsula, to outward bending in the
      southeastern species, and to oval or reniform with inward bending in the northern
      species.

PMID- 19746443
TI  - Assessment of organochlorine pesticides and metals in ring-tailed lemurs (Lemur
      catta) at Beza Mahafaly Special Reserve, Madagascar.
AB  - Like most of Madagascar's endemic primates, ring-tailed lemurs (Lemur catta) face
      a number of threats to their survival. Although habitat loss is of greatest
      concern, other anthropogenic factors including environmental contamination may
      also affect lemur health and survival. In this study, we examined ring-tailed
      lemurs from the Beza Mahafaly Special Reserve (BMSR), southern Madagascar for
      exposure to organochlorine (OC) pesticides and metals and examined differences in
      contaminant concentrations between sexes and among age groups, troops, and
      habitats. A total of 14 pesticides and 13 metals was detected in lemur blood (24
      individuals) and hair (65 individuals) samples, respectively. p,p'-DDT,
      heptachlor, aldrin, heptachlor epoxide, endrin aldehyde, and endrin were among
      the most prevalent pesticides detected. Surprisingly, the persistent metabolite
      of p,p'-DDT, p,p'-DDE, was not detected. The most commonly detected metals were
      aluminum, zinc, boron, phosphorus, silicon, and copper, whereas metals considered
      more hazardous to wildlife (e.g. arsenic, cadmium, lead, selenium, vanadium) were
      not found above detection limits. Overall, concentrations of OC pesticides and
      metals were low and similar to those considered to be background concentrations
      in other studies examining the ecotoxicology of wild mammals. Few inter-sex, 
      age, -troop, and -habitat differences in contaminant concentrations were
      observed, suggesting a uniform distribution of contaminants within the reserve.
      Several statistically significant relationships between lemur body size and
      contaminant concentrations were observed, but owing to the lack of supportive
      data regarding contaminant exposure in wild primates, the biological significance
      of these findings remains uncertain. Results of this study document exposure of
      ring-tailed lemurs at BMSR to multiple OC pesticides and metals and provide
      essential baseline data for future health and toxicological evaluations of lemurs
      and other wild primates, especially those in regions with expanding agricultural
      and mining operations.

PMID- 19746444
TI  - Runx2, p53, and pRB status as diagnostic parameters for deregulation of
      osteoblast growth and differentiation in a new pre-chemotherapeutic osteosarcoma
      cell line (OS1).
AB  - Osteosarcomas are the most prevalent primary bone tumors found in pediatric
      patients. To understand their molecular etiology, cell culture models are used to
      define disease mechanisms under controlled conditions. Many osteosarcoma cell
      lines (e.g., SAOS-2, U2OS, MG63) are derived from Caucasian patients. However,
      patients exhibit individual and ethnic differences in their responsiveness to
      irradiation and chemotherapy. This motivated the establishment of osteosarcoma
      cell lines (OS1, OS2, OS3) from three ethnically Chinese patients. OS1 cells,
      derived from a pre-chemotherapeutic tumor in the femur of a 6-year-old female,
      were examined for molecular markers characteristic for osteoblasts, stem cells,
      and cell cycle control by immunohistochemistry, reverse transcriptase-PCR,
      Western blotting and flow cytometry. OS1 have aberrant G-banded karyotypes,
      possibly reflecting chromosomal abnormalities related to p53 deficiency. OS1 had
      ossification profiles similar to human fetal osteoblasts rather than SAOS-2 which
      ossifies ab initio (P < 0.05). Absence of p53 correlates with increased Runx2
      expression, while the slow proliferation of OS1 cells is perhaps attenuated by
      pRB retention. OS1 express mesenchymal stem cell markers (CD44, CD105) and differ
      in relative expression of CD29, CD63, and CD71 to SAOS-2. (P < 0.05). Cell cycle
      synchronization with nocodazole did not affect Runx2 and CDK1 levels but
      decreased cyclin-E and increased cyclin-A (P < 0.05). Xenotransplantion of OS1 in
      SCID mice yields spontaneous tumors that were larger and grew faster than SAOS-2
      transplants. Hence, OS1 is a new osteosarcoma cell culture model derived from a
      pre-chemotherapeutic ethnic Chinese patient, for mechanistic studies and
      development of therapeutic strategies to counteract metastasis and deregulation
      of mesenchymal development.

PMID- 19746445
TI  - Real-time fetal magnetic resonance imaging for the dynamic visualization of the
      pouch in esophageal atresia.
AB  - Esophageal atresia is the principal cause of congenital esophageal obstruction.
      Prenatal suspicion of esophageal atresia is usually based on the presence of
      polyhydramnios together with an absent stomach bubble. More recently,
      visualization of the dilatation of the blind-ending esophagus (esophageal pouch)
      during fetal swallowing has been reported and proposed as the most reliable sign
      for predicting esophageal atresia. Improvement of radiofrequency and computer
      technology as well as parallel data acquisition has greatly reduced magnetic
      resonance (MR) scanning time, allowing visualization of the fetus in cine-mode
      using fast imaging employing steady-state acquisition (FIESTA). We describe the
      application of FIESTA sequences in fetuses with suspected esophageal atresia for
      visualization of the esophageal pouch using MR imaging.

PMID- 19746446
TI  - The mammalian anti-proliferative BTG/Tob protein family.
AB  - The mammalian BTG/Tob family comprises six proteins (BTG1, BTG2/PC3/Tis21,
      BTG3/ANA, BTG4/PC3B, Tob1/Tob and Tob2), which regulate cell cycle progression in
      a variety of cell types. They are characterised by the conserved N-terminal
      domain spanning 104-106 amino acids. Recent biochemical and structural data
      indicate that the conserved BTG domain is a protein-protein interaction module,
      which is capable of binding to DNA-binding transcription factors as well as the
      paralogues CNOT7 (human Caf1/Caf1a) and CNOT8 (human Pop2/Calif/Caf1b), two
      deadenylase subunits of the Ccr4-Not complex. Consistent with this finding,
      several members of the BTG/Tob family are shown to be implicated in transcription
      in the nucleus and cytoplasmic mRNA deadenylation and turnover. The C-terminal
      regions are less conserved and appear to mediate protein-protein interactions
      that are unique to each family member. The human and mouse BTG/Tob proteins will
      be the focus of this review and structural aspects of BTG/Tob interactions with
      components of the Ccr4-Not complex, and the role of the BTG/Tob proteins in the
      regulation of gene expression, tumourigenesis and cancer will be discussed.

PMID- 19746447
TI  - Runx2-mediated bcl-2 gene expression contributes to nitric oxide protection
      against hydrogen peroxide-induced osteoblast apoptosis.
AB  - Nitric oxide (NO) can regulate osteoblast activities. This study was aimed to
      evaluate the protective effects of pretreatment with sodium nitroprusside (SNP)
      as a source of NO on hydrogen peroxide-induced osteoblast insults and its
      possible mechanisms. Exposure of human osteosarcoma MG63 cells to hydrogen
      peroxide significantly increased cellular oxidative stress, but decreased ALP
      activity and cell viability, inducing cell apoptosis. Pretreatment with 0.3 mM
      SNP significantly lowered hydrogen peroxide-induced cell insults. Treatment of
      human MG63 cells with hydrogen peroxide inhibited Bcl-2 mRNA and protein
      production, but pretreatment with 0.3 mM SNP significantly ameliorated such
      inhibition. Sequentially, hydrogen peroxide decreased the mitochondrial membrane
      potential, but increased the levels of cytochrome c and caspase-3 activity.
      Pretreatment with 0.3 mM SNP significantly lowered such alterations. Exposure to
      hydrogen peroxide decreased Runx2 mRNA and protein syntheses. However,
      pretreatment with 0.3 mM SNP significantly lowered the suppressive effects. Runx2
      knockdown using RNA interference inhibited Bcl-2 mRNA production in human MG63
      cells. Protection of pretreatment with 0.3 mM SNP against hydrogen peroxide
      induced alterations in ALP activity, caspase-3 activity, apoptotic cells, and
      cell viability were also alleviated after administration of Runx2 small
      interference RNA. Thus, this study shows that pretreatment with 0.3 mM SNP can
      protect human MG63 cells from hydrogen peroxide-induced apoptotic insults
      possibly via Runx2-involved regulation of bcl-2 gene expression.

PMID- 19746448
TI  - Physiological and coordinate downregulation of the NPC1 and NPC2 genes are
      associated with the sequestration of LDL-derived cholesterol within endocytic
      compartments.
AB  - The Niemann-Pick C1 and C2 (NPC1 and NPC2) proteins have a central role in
      regulating the transport of lipoprotein-derived cholesterol from endocytic
      compartments to the endoplasmic reticulum for esterification by acyl
      CoA:cholesterol acyltransferase (ACAT) and feedback inhibition of the sterol
      regulatory element-binding protein (SREBP) pathway. Since the NPC1 gene/protein
      has recently been shown to be downregulated by feedback inhibition of the SREBP
      pathway, the present study was performed to determine whether physiological
      downregulation of the NPC1 gene/protein alters the transport and metabolism of
      low-density lipoprotein (LDL)-derived cholesterol in human fibroblasts. To
      perform this study, three different culture conditions were used that included
      fibroblasts grown in lipoprotein-deficient serum (LPDS), LPDS supplemented with
      LDL, and LPDS supplemented with LDL, followed by equilibration in the absence of
      LDL to allow the transport of LDL-derived cholesterol from endocytic compartments
      and equilibration of cellular sterol pools. The results from this study indicated
      that in addition to the NPC1 gene/protein, the NPC2 gene/protein was also
      downregulated by LDL-derived cholesterol-dependent feedback inhibition and that
      downregulation of both the NPC1 and NPC2 genes/proteins was associated with the
      sequestration of LDL-derived cholesterol within endocytic compartments, including
      late endosomes/lysosomes after equilibration. Therefore, it is proposed that
      physiological and coordinate downregulation of the NPC1 and NPC2 genes/proteins
      promotes the sequestration of LDL-derived cholesterol within endocytic
      compartments and serves a role in maintaining intracellular cholesterol
      homeostasis.

PMID- 19746449
TI  - A cell-based Dkk1 binding assay reveals roles for extracellular domains of LRP5
      in Dkk1 interaction and highlights differences between wild-type and the high
      bone mass mutant LRP5(G171V).
AB  - Dkk1 is a secreted antagonist of the LRP5-mediated Wnt signaling pathway that
      plays a pivotal role in bone biology. Because there are no well-documented LRP5
      based assays of Dkk1 binding, we developed a cell-based assay of Dkk1/LRP5
      binding using radioactive (125)I-Dkk1. In contrast to LRP6, transfection of LRP5
      alone into 293A cells resulted in a low level of specific binding that was
      unsuitable for routine assay. However, co-transfection of LRP5 with the chaperone
      protein MesD (which itself does not bind Dkk1) or Kremen-2 (a known Dkk1
      receptor), or both, resulted in a marked enhancement of specific binding that was
      sufficient for evaluation of Dkk1 antagonists. LRP5 fragments comprising the
      third and fourth beta-propellers plus the ligand binding domain, or the first
      beta-propeller, each inhibited Dkk1 binding, with mean IC(50)s of 10 and 196 nM,
      respectively. The extracellular domain of Kremen-2 ("soluble Kremen") was a
      weaker antagonist (mean IC(50) 806 nM). We also found that cells transfected with
      a high bone mass mutation LRP5(G171V) had a subtly reduced level of Dkk1 binding,
      compared to wild type LRP5-transfected cells, and no enhancement of binding by
      MesD. We conclude that (1) LRP5-transfected cells do not offer a suitable cell
      based Dkk1 binding assay, unless co-transfected with either MesD, Kremen-2, or
      both; (2) soluble fragments of LRP5 containing either the third and fourth beta
      propellers plus the ligand binding domain, or the first beta-propeller,
      antagonize Dkk1 binding; and (3) a high bone mass mutant LRP5(G171V), has subtly
      reduced Dkk1 binding, and, in contrast to LRP5, no enhancement of binding with
      MesD.

PMID- 19746450
TI  - Use of ultrasound pattern recognition by expert operators to identify borderline
      ovarian tumors: a study of diagnostic performance and interobserver agreement.
AB  - OBJECTIVE: To assess the accuracy and reproducibility of ultrasound 'pattern
      recognition' for the diagnosis of borderline ovarian tumors by asking experienced
      ultrasound operators to evaluate representative images of different types of
      adnexal tumor. METHODS: Digitally stored static two-dimensional B-mode images of
      representative cases of benign, borderline and invasive malignant ovarian tumors
      were independently assessed by three expert sonologists who had not performed the
      original real-time ultrasound examination. The outcome measures included
      diagnostic accuracy and interobserver agreement in the diagnosis of benign,
      borderline or invasive malignant ovarian tumors. RESULTS: One hundred and sixty
      six cases were included in the final data analysis. A correct classification was
      made by all three experts in 83% of the primary invasive cancers, 76% of the
      benign masses and in 44% of the borderline malignant tumors (P < 0.01). The
      experts showed a tendency to misclassify borderline tumors as benign rather than
      primary invasive (ratio of 8 : 1 for Expert A, 4 : 1 for B and 6 : 1 for C). The
      interobserver agreement between any two experts was very good when they were
      tested for their ability to discriminate between invasive and non-invasive
      (benign and borderline) ovarian tumors (Cohen's kappa 0.85-0.88), but poorer for
      the discrimination between malignant (invasive and borderline) and benign tumors
      (kappa 0.70-0.78). CONCLUSIONS: The accuracy of ultrasound diagnosis of
      borderline tumors is lower in comparison with benign and invasive malignant
      lesions. The diagnostic performance and interobserver agreement are better when
      the outcomes are dichotomized into non-invasive and invasive malignant lesions,
      as opposed to the traditional diagnosis of benign and malignant tumors.

PMID- 19746451
TI  - Thyroid follicular neoplasms: can sonography distinguish between adenomas and
      carcinomas?
AB  - PURPOSE: The purpose of this study was to determine whether sonography (US) can
      usefully differentiate thyroid follicular adenoma (FA) and follicular carcinoma
      (FC). METHODS: This retrospective study included 60 pathologically proven FAs and
      66 FCs in 123 consecutive patients (17 males and 106 females) with a mean age of
      47 +/- 13 years, (17-73 years) who underwent thyroid surgery. We analyzed US
      features of each nodule, including maximum diameter, echogenicity, composition,
      presence of calcification, margins, and presence of halo. The frequencies of each
      US feature were compared by using the chi(2) test or Fisher's exact test between
      FAs and FCs. The relative risk of malignancy was evaluated by logistic regression
      analysis. RESULTS: Isohypoechoic echogenicity, predominantly solid or mixed
      echotexture, and presence of microcalcifications or rim calcifications were
      associated with FC (p < 0.05). Logistic regression analysis demonstrated that
      predominantly solid or mixed echotexture and microcalcifications or rim
      calcifications were associated with significant increases in relative risk for FC
      (odds ratio 8.1 and odds ratio 13.5, respectively, p < 0.01). CONCLUSIONS: The US
      features of isohypoechoic echogenicity, predominantly solid or mixed echotexture,
      and microcalcifications or rim calcifications are more common in FC than in FA.

PMID- 19746452
TI  - Postural tremor in X-linked spinal and bulbar muscular atrophy.
AB  - Postural tremor is a common initial symptom in spinal and bulbar muscular atrophy
      (SBMA), but its pathophysiological mechanisms remain to be studied. This study
      was undertaken to examine the physiological mechanisms underlying postural tremor
      in SBMA. For eight patients (36-63 years old) with genetically confirmed SBMA, we
      recorded surface electromyograms (EMGs) from the forearm muscles and hand
      movements with an accelerometer (ACC) while maintaining a posture with and
      without a weight load. We then analyzed their power spectra and coherence. The
      peak tremor frequency was 6-9 Hz in seven patients and 2-3 Hz in one patient.
      Oscillatory movements were associated with EMG activity in five patients, but not
      in three patients. Weight loads and postural changes affected the tremor
      frequency in all patients. Tremor was classified as "reflex tremor" in five
      patients and "mechanical tremor" in three patients. These results suggest that
      peripheral factors play important roles in tremor genesis in SBMA, although its
      clinical features resemble essential tremor. Subclinical sensory disturbance or a
      decrease of motor unit numbers might be candidates for such peripheral factors
      contributing to tremor genesis in SBMA.

PMID- 19746453
TI  - Hepatofugal portal flow on Doppler sonography in various pathological conditions:
      a pictorial essay.

PMID- 19746454
TI  - Pediatric rhabdomyosarcoma in Morocco.
AB  - BACKGROUND: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in the
      first two decades of life. There is, however, a paucity of reports on the pattern
      of its occurrence in Africa. This study analyses the epidemiological pattern,
      clinical features, histology, and outcome in Moroccan children presenting with
      RMS. METHODS: We retrospectively studied 100 consecutive cases of histologically
      proven RMS in previously untreated children <15 years old followed at the
      Pediatric Oncology Unit of the Children's Hospital of Rabat from January 1995 to
      December 2004. RESULTS: RMS represented 5% of all the patients treated for cancer
      during this period. The male/female ratio was 2:1 with a mean age at diagnosis of
      5 years. The embryonal subtype was the most frequent (73%) and the head and neck
      was the most common site of disease, followed by the genito-urinary tract and
      limbs. Chemotherapy was used in all patients; 44% also had a radical surgery and
      23% radiation therapy. The event-free survival (EFS) at 10 years was 39% with
      relapse as the first cause of treatment failure. The overall survival at 10 years
      was 70%. The rate of treatment abandonment was 37%. CONCLUSION: Epidemiology and
      clinical features of RMS in Moroccan children does not differ from others
      countries. However, EFS is lower than that reported elsewhere due to occasional
      lack of availability of drugs, inadequate local control, and abandonment.

PMID- 19746455
TI  - Evaluation of the hepatic artery anastomosis by intraoperative sonography with
      high-frequency transducer in right-lobe graft living donor liver transplantation.
AB  - OBJECTIVE: To describe the usefulness of intraoperative ultrasonography (IOUS)
      with high-frequency transducer in living donor liver transplantation (LDLT) using
      right-lobe graft (RLG). METHOD: This retrospective study was approved by our
      institutional review board. We performed IOUS in 22 patients (17 men and 5 women,
      aged 51 +/- 9.0 years) during LDLT with RLG using a Sequoia 512 scanner with an 8
      12-MHz linear transducer. Hepatic artery (HA) anastomosis was identified on gray
      scale US, and the diameter and percentage of stenosis of the anastomosis were
      measured. The HA was evaluated to detect thrombus or dissection in the region of
      anastomosis. Doppler study of the graft HA was also performed. Patients were
      divided into those with and without abnormalities, including thrombosis,
      dissection, and abnormal Doppler parameters (peak systolic velocity < 30 cm/s or
      > 2 m/s, resistance index < 0.5, and systolic acceleration time > 80 msec).
      RESULT: On gray-scale and Doppler IOUS study, abnormalities were found in 10 of
      22 patients. Diagnoses were anastomotic stenosis (n = 2), celiac stenosis (n =
      1), compromise of HA inflow due to systemic hypotension (n = 1), HA thrombosis (n
      = 2), and HA dissection (n = 4). Re-anastomoses were done in 3 case (2 stenoses
      and 1 thrombosis). Uneventful postoperative recovery occurred in the other 7
      patients without re-anastomosis. CONCLUSION: IOUS with high-frequency transducer
      is a useful method to make an early diagnosis of HA complications of LDLT with
      RLG.

PMID- 19746456
TI  - Trumpet maneuver in the sonographic diagnosis of an external laryngocele.
AB  - Laryngocele is an uncommon disease defined as an abnormal dilatation or
      herniation of the laryngeal saccule, forming an air-filled cavity. Radiologic
      evaluation of a suspected laryngocele generally includes plain radiographs, CT,
      and MRI. There are very few reports in the literature on sonographic findings of
      laryngocele. Trumpet maneuver has been reported in CT examination for the
      diagnosis of laryngocele. However, to the best of our knowledge, the use of
      trumpet maneuver in the sonographic diagnosis of laryngocele has not been
      previously described. This report presents the sonographic findings of an
      external laryngocele while performing the trumpet maneuver.

PMID- 19746457
TI  - The utility of thoracic ultrasound before local anesthetic video-assisted
      thoracoscopy in patients with suspected pleural malignancy.
AB  - Video-assisted thoracoscopy under local anesthesia (VAT-LA) is a key
      investigation in the diagnosis and management of suspected malignant pleural
      effusion. Two problems encountered at VAT-LA are accessing the pleural space and
      fibrinous intrapleural septa. Thoracic sonography (TUS) is known to facilitate
      thoracocentesis after dry tap but has not been studied in detail before VAT-LA.
      We report a case of lateral decubitus pre-VAT TUS that helped locate the optimal
      access to the pleural space and demonstrated fibrinous intrapleural septation,
      thereby affecting the decision to avoid thoracoscopic pleurodesis.

PMID- 19746458
TI  - Variations of the origin of renal arteries in the fetus identified on power
      Doppler and 3D sonography.
AB  - PURPOSE: To investigate anatomic variations of renal arteries (RAs) using 2
      dimensional (2D)/3D power Doppler sonography (PDUS) in normal fetuses and in
      fetuses with renal anomalies. METHODS: The origin, direction, and distribution of
      RAs were studied in 120 fetuses without renal malformations using 2D/3D PDUS.
      Studies were performed between 14 and 17 weeks of gestation age on 64 male and 56
      female fetuses. PDUS of the RAs was also performed in 12 fetuses with renal
      anomalies. RESULTS: In 117/120 fetuses, a single RA was found to originate from
      each side of the abdominal aorta. The origin of the right RA from the abdominal
      aorta was superior to, at the same level as, and inferior to that of the left RA
      in 47% (55/117), 25.5% (30/117), and 27.5% (32/117) of the cases, respectively.
      An accessory right RA was found in 3 cases. Bifurcation of the right RA was found
      in 2 cases. There were no variations of the origin of renal vessels in 69% of the
      cases (83/120), whereas the remaining 31% (37/120) had 1 or several variation
      patterns. Variations in renal vessels were found in 8 of the 12 fetuses with
      renal malformations: accessory artery in 3 cases, origin of the right RA from the
      iliac artery in horseshoe kidney and in 2 cases with pelvic kidney, and
      bifurcation in 2 of the fetuses with double collecting system. CONCLUSIONS:
      Variations in origin and distribution of fetal RAs are frequently observed in
      normal pregnancies. The majority of renal malformations are associated with such
      vascular variations.

PMID- 19746459
TI  - Synthesis, structure, and highly efficient copper-catalyzed aziridination with a
      tetraaza-bispidine ligand.
AB  - The distorted trigonal-bipyramidal Cu(II) complex [Cu(L(1))(NCCH(3))](2+) of the
      novel tetradentate bispidine-derived ligand L(1) with four tertiary amine donors
      (L(1)=1,5-diphenyl-3-methyl-7-(1,4,6-trimethyl-1,4-diazacycloheptane-6
      yl)diazabicyclo[3.3.1]nonane-9-one) is a very efficient catalyst for the
      aziridination of olefins in the presence of a nitrene source. In agreement with
      the experimental data (in situ spectroscopy, product distribution, and its
      dependence on the geometry of the substrate and of the nitrene source), a
      theoretical analysis based on DFT calculations indicates that the active catalyst
      has the Cu center in its +II oxidation state, that electron transfer is not
      involved, and that the conversion of the olefin to an aziridine is a stepwise
      process involving a radical intermediate. The striking change of efficiency and
      reaction mechanism between classical copper-bispidine complexes and the novel
      L(1)-based catalyst is primarily attributed to the structural variation, enforced
      by the ligand architecture.

PMID- 19746460
TI  - The role of one-electron reduction of lipid hydroperoxides in causing DNA damage.
AB  - The in vivo metabolism of plasma lipids generates lipid hydroperoxides that, upon
      one-electron reduction, give rise to a wide spectrum of genotoxic unsaturated
      aldehydes and epoxides. These metabolites react with cellular DNA to form a
      variety of pre-mutagenic DNA lesions. The mechanisms of action of the radical
      precursors of these genotoxic electrophiles are poorly understood. In this work
      we investigated the nature of DNA products formed by a one-electron reduction of
      (13S)-hydroperoxy-(9Z,11E)-octadecadienoic acid (13S-HPODE), a typical lipid
      molecule, and the reactions of the free radicals thus generated with neutral
      guanine radicals, G(-H)(*). A novel approach was devised to generate these
      intermediates in solution. The two-photon-induced ionization of 2-aminopurine
      (2AP) within the 2'-deoxyoligonucleotide 5'-d(CC[2AP]TCGCTACC) by intense
      nanosecond 308 nm excimer laser pulses was employed to simultaneously generate
      hydrated electrons and radical cations 2AP(*+). The latter radicals either in
      cationic or neutral forms, rapidly oxidize the nearby G base to form G(-H)(*). In
      deoxygenated buffer solutions (pH 7.5), the hydrated electrons rapidly reduce 13S
      HPODE and the highly unstable alkoxyl radicals formed undergo a prompt beta
      scission to pentyl radicals that readily combine with G(-H)(*). Two novel guanine
      products in these oligonucleotides, 8-pentyl- and N(2)-pentylguanine, were
      identified. It is shown that the DNA secondary structure significantly affects
      the ratio of 8-pentyl- and N(2)-pentylguanine lesions that changes from 0.9:1 in
      single-stranded, to 1:0.2 in double-stranded oligonucleotides. The alkylation of
      guanine by alkyl radicals derived from lipid hydroperoxides might contribute to
      the genotoxic modification of cellular DNA under hypoxic conditions. Thus,
      further research is warranted on the detection of pentylguanine lesions and other
      alkylguanines in vivo.

PMID- 19746461
TI  - Dinitrogen activation by Fryzuk's [Nb(P(2)N(2))] complex and comparison with the
      Laplaza-Cummins [Mo{N(R)Ar}(3)] and Schrock [Mo(N(3)N)] systems.
AB  - The reaction profile of N(2) with Fryzuk's [Nb(P(2)N(2))]
      (P(2)N(2)=PhP(CH(2)SiMe(2)NSiMe(2)CH(2))(2)PPh) complex is explored by density
      functional calculations on the model [Nb(PH(3))(2)(NH(2))(2)] system. The effects
      of ligand constraints, coordination number, metal and ligand donor atom on the
      reaction energetics are examined and compared to the analogous reactions of N(2)
      with the three-coordinate Laplaza-Cummins [Mo{N(R)Ar}(3)] and four-coordinate
      Schrock [Mo(N(3)N)] (N(3)N=[(RNCH(2)CH(2))(3)N](3-)) systems. When the model
      system is constrained to reflect the geometry of the P(2)N(2) macrocycle, the N-
      N bond cleavage step, via a N(2)-bridged dimer intermediate, is calculated to be
      endothermic by 345 kJ mol(-1). In comparison, formation of the single-N-bridged
      species is calculated to be exothermic by 119 kJ mol(-1), and consequently is the
      thermodynamically favoured product, in agreement with experiment. The orientation
      of the amide and phosphine ligands has a significant effect on the overall
      reaction enthalpy and also the N--N bond cleavage step. When the ligand
      constraints are relaxed, the overall reaction enthalpy increases by 240 kJ mol(
      1), but the N(2) cleavage step remains endothermic by 35 kJ mol(-1). Changing the
      phosphine ligands to amine donors has a dramatic effect, increasing the overall
      reaction exothermicity by 190 kJ mol(-1) and that of the N--N bond cleavage step
      by 85 kJ mol(-1), making it a favourable process. Replacing Nb(II) with Mo(III)
      has the opposite effect, resulting in a reduction in the overall reaction
      exothermicity by over 160 kJ mol(-1). The reaction profile for the model
      [Nb(P(2)N(2))] system is compared to those calculated for the model Laplaza and
      Cummins [Mo{N(R)Ar}(3)] and Schrock [Mo(N(3)N)] systems. For both [Mo(N(3)N)] and
      [Nb(P(2)N(2))], the intermediate dimer is calculated to lie lower in energy than
      the products, although the final N-N cleavage step is much less endothermic for
      [Mo(N(3)N)]. In contrast, every step of the reaction is favourable and the
      overall exothermicity is greatest for [Mo{N(R)Ar}(3)], and therefore this system
      is predicted to be most suitable for dinitrogen cleavage.

PMID- 19746462
TI  - 1-Phenyl-1,2-cyclohexadiene: generation, interception by activated olefins,
      dimerisation and trimerisation.
AB  - Four possible precursors of 1-phenyl-1,2-cyclohexadiene (2) were examined,
      namely, 6,6-dibromo-1-phenylbicyclo[3.1.0]hexane, (1alpha,5alpha,6alpha)-6-bromo
      6-fluoro-1-phenylbicyclo[3.1.0]hexane, 1-bromo-2-phenylcyclohexene and 1-bromo-6
      phenylcyclohexene. All four compounds could be converted into 2, as demonstrated
      by the products of the interception of 2 with activated olefins. Styrene, 1,1
      diphenylethene, indene, furan and 2,5-dimethylfuran were employed as such.
      Whereas the first three gave [2+2] cycloadducts of 2, the last two provided one
      [4+2] cycloadduct each. To create the [2+2] cycloadducts, the pi bond of 2 that
      is more remote from the phenyl group reacted, whereas the pi bond of 2 conjugated
      with the phenyl group exclusively produced the [4+2] cycloadducts. The generation
      of 2 in the absence of a trapping reagent brought about relatively good yields of
      a dimer or a trimer of 2 depending on the mode of the liberation of 2. Being
      derivatives of triphenylene, the dimer as well as the trimer have unusual
      structures, thereby indicating that a phenyl group is participating in the
      formation of these compounds. The most surprising structure of the trimer was
      elucidated by X-ray crystal diffraction. As to the mechanisms, diradical
      intermediates are proposed both for the cycloadditions and for the dimerisation.
      The initial steps of the latter seem to proceed also in the trimerisation.

PMID- 19746463
TI  - 1-Phenyl-1,2-cyclohexadiene: astoundingly high enantioselectivities on generation
      in a Doering-Moore-Skattebol reaction and interception by activated olefins.
AB  - The resolution of (1alpha,5alpha,6alpha)-6-bromo-6-fluoro-1
      phenylbicyclo[3.1.0]hexane (rac-5) provided the enantiomerically pure precursors
      (-)-5 and (+)-5 of 1-phenyl-1,2-cyclohexadiene. On treatment of (-)-5 with
      methyllithium in the presence of 2,5-dimethylfuran, the pure (-)-enantiomer of
      the [4+2] cycloadduct of 2,5-dimethylfuran onto 1-phenyl-1,2-cyclohexadiene was
      obtained exclusively. From this result, it is concluded that pure (M)-1-phenyl
      1,2-cyclohexadiene ((M)-7) emerged from (-)-5 and was enantiospecifically
      intercepted to give the product. In the case of indene as trap for (M)-7, the (-)
      and the (+)-enantiomer of the [2+2] cycloadduct were formed in the ratio of
      95:5. Highly surprising, remarkable enantioselectivities were also observed, when
      (M)-7 was trapped with styrene to furnish two diastereomeric [2+2] cycloadducts.
      Hence, the achiral conformation of the diradical conceivable as intermediate
      cannot play a decisive part. The enantioselective generation of (M)- and (P)-7 by
      the beta-elimination route was tested as well. Accordingly, 1-bromo-2
      phenylcyclohexene was exposed to the potassium salt of (-)-menthol in the
      presence of 2,5-dimethylfuran, and the enantiomeric [4+2] cycloadducts of the
      latter onto (M)- and (P)-7 were produced in the ratio of 55:45.

PMID- 19746464
TI  - Stabilisation of Peptide foldamers in an aqueous medium by incorporation of
      azapeptide building blocks.

PMID- 19746465
TI  - Chiral catalysts dually functionalized with amino acid and Zn2+ complex
      components for enantioselective direct aldol reactions inspired by natural
      aldolases: design, synthesis, complexation properties, catalytic activities, and
      mechanistic study.
AB  - Aldolases are enzymes that catalyze stereospecific aldol reactions in a
      reversible manner. Naturally occurring aldolases include class I aldolases, which
      catalyze aldol reactions via enamine intermediates, and class II aldolases, in
      which Zn(2+) enolates of substrates react with acceptor aldehydes. In this work,
      Zn(2+) complexes of L-prolyl-pendant[15]aneN(5) (ZnL(3)), L-prolyl
      pendant[12]aneN(4) (ZnL(4)), and L-valyl-pendant[12]aneN(4) (ZnL(5)) were
      designed and synthesized for use as chiral catalysts for enantioselective aldol
      reactions. The complexation constants for L(3) to L(5) with Zn(2+) [logK(s)(ZnL)]
      were determined to be 14.1 (for ZnL(3)), 7.6 (for ZnL(4)), and 9.6 (for ZnL(5)),
      indicating that ZnL(3) is more stable than ZnL(4) and ZnL(5). The deprotonation
      constants of Zn(2+)-bound water [pK(a)(ZnL) values] for ZnL(3), ZnL(4), and
      ZnL(5) were calculated to be 9.2 (for ZnL(3)), 8.2 (for ZnL(4)), and 8.6 (for
      ZnL(5)), suggesting that the Zn(2+) ions in ZnL(3) is a less acidic Lewis acid
      than in ZnL(4) and ZnL(5). These values also indicated that the amino groups on
      the side chains weakly coordinate to Zn(2+). We carried out aldol reactions
      between acetone and 2-chlorobenzaldehyde and other aldehydes in the presence of
      catalytic amounts of the chiral Zn(2+) complexes in acetone/H(2)O at 25 and 37
      degrees C. Whereas ZnL(3) yielded the aldol product in 43% yield and 1% ee (R),
      ZnL(4) and ZnL(5) afforded good chemical yields and high enantioselectivities of
      up to 89% ee (R). UV titrations of proline and ZnL(4) with acetylacetone (acac)
      in DMSO/H(2)O (1:2) indicate that ZnL(4) facilitates the formation of the
      ZnL(4)(acac)(-) complex (K(app)=2.1x10(2) M(-1)), whereas L-proline forms a
      Schiff base with acac with a very small equilibrium constant. These results
      suggest that the amino acid components and the Zn(2+) ions in ZnL(4) and ZnL(5)
      function in a cooperative manner to generate the Zn(2+)-enolate of acetone, thus
      permitting efficient enantioselective C-C bond formation with aldehydes.

PMID- 19746466
TI  - N-fusion approach in construction of contracted carbaporphyrinoids: formation of
      N-fused telluraporphyrin.
AB  - Insertion of PCl(3) into 5,10,15,20-tetraaryl-21-telluraporphyrin leads to a
      phosphorus complex of N-fused dihydrotelluraporphyrin with an inverted
      tellurophene ring. Its CNN coordination core places the macrocycle in the family
      of contracted carbaporphyrinoids. A cycle of direct transformations affords an
      elegant triangle of three mutually convertible N-fused porphyrinoids, with
      distinct spectroscopic features: antiaromatic, nonaromatic and aromatic. The
      nonaromatic species has a dome shaped skeleton which forms in the solid state a
      ball and socket structure with C(60).

PMID- 19746467
TI  - Reversible adsorption and separation of aromatics on Cd(II)-triazole single
      crystals.

PMID- 19746468
TI  - Examination of the effect of the annealing cation on higher order structures
      containing guanine or isoguanine repeats.
AB  - Isoguanine (2-oxo-6-amino-guanine), a natural but non-standard base, exhibits
      unique self-association properties compared to its isomer, guanine, and results
      in formation of different higher order DNA structures. In this work, the higher
      order structures formed by oligonucleotides containing guanine repeats or
      isoguanine repeats after annealing in solutions containing various cations are
      evaluated by electrospray ionization mass spectrometry (ESI-MS) and circular
      dichroism (CD) spectroscopy. The guanine-containing strand (G9) consistently
      formed quadruplexes upon annealing, whereas the isoguanine strand (Ig9) formed
      both pentaplexes and quadruplexes depending on the annealing cation. Quadruplex
      formation with G9 showed some dependence on the identity of the cation present
      during annealing with high relative quadruplex formation detected with six of ten
      cations. Analogous annealing experiments with Ig9 resulted in complex formation
      with all ten cations, and the majority of the resulting complexes were
      pentaplexes. CD results indicated most of the original complexes survived the
      desalting process necessary for ESI-MS analysis. In addition, several complexes,
      especially the pentaplexes, were found to be capable of cation exchange with
      ammonium ions. Ab initio calculations were conducted for isoguanine tetrads and
      pentads coordinated with all ten cations to predict the most energetically stable
      structures of the complexes in the gas phase. The observed preference of forming
      quadruplexes versus pentaplexes as a function of the coordinated cation can be
      interpreted by the calculated reaction energies of both the tetrads and pentads
      in combination with the distortion energies of tetrads.

PMID- 19746469
TI  - Alpha-O-linked glycopeptide mimetics: synthesis, conformation analysis, and
      interactions with viscumin, a galactoside-binding model lectin.
AB  - Efficient cycloaddition of a silylidene-protected galactal with a suitable
      heterodiene yielded the basis for a facile diastereoselective route to a
      glycopeptide-mimetic scaffold. Its carbohydrate part was further extended by
      beta1-3-linked galactosylation. The pyranose rings retain their (4)C(1) chair
      conformation, as shown by molecular modeling and NMR spectroscopy, and the
      typical exo-anomeric geometry was observed for the disaccharide. The expected
      bioactivity was ascertained by saturation-transfer-difference NMR spectroscopy by
      using the galactoside-specific plant toxin viscumin as a model lectin. The
      experimental part was complemented by molecular docking. The described synthetic
      route and the strategic combination of computational and experimental techniques
      to reveal conformational properties and bioactivity establish the prepared alpha
      O-linked glycopeptide mimetics as promising candidates for further exploitation
      of this scaffold to give O-glycans for lectin blocking and vaccination.

PMID- 19746470
TI  - Design and synthesis of urea-linked aromatic oligomers--a route towards
      convoluted foldamers.
AB  - Herein we report the design and synthesis of crescent-shaped and helical urea
      based foldamers, the curvature of which is controlled by varying the constituent
      building blocks and their connectivity. These oligomers are comprised of two,
      three or five alternating aromatic heterocycles (pyridazine, pyrimidine or
      pyrazine) and methyl-substituted aromatic carbocycles (tolyl, o-xylyl or m-xylyl)
      connected together through urea linkages. A crescent-shaped conformational
      preference is encoded within these pi-conjugated urea-linked oligomers based on
      intramolecular hydrogen bonding and steric interactions; the degree of curvature
      is tuned by the urea connectivity to the heterocycles and the aryl groups. NMR
      characterization of these foldamers confirms the intramolecular hydrogen-bonded
      conformation expected (Z,E configuration of the urea bond) in both the pyridazyl
      and pyrimidyl foldamers in solution. An X-ray crystal structure of the N(3),N(6)
      diisobutylpyridazine-4,6-diamine-o-tolyl urea-linked foldamer (4) confirms the
      presence of N-H...N hydrogen bonds between the heterocyclic nitrogen atom and the
      free hydrogen of the urea linkage. Additionally, the tolyl methyl group interacts
      unfavourably with the urea carbonyl oxygen, thus destabilising the alternate
      planar conformation.

PMID- 19746471
TI  - Low-concentration 1,2-trans beta-selective glycosylation strategy and its
      applications in oligosaccharide synthesis.
AB  - This study develops an operationally easy, efficient, and general 1,2-trans beta
      selective glycosylation reaction that proceeds in the absence of a C2 acyl
      function. This process employs chemically stable thioglycosyl donors and low
      substrate concentrations to achieve excellent beta-selectivities in glycosylation
      reactions. This method is widely applicable to a range of glycosyl substrates
      irrespective of their structures and hydroxyl-protecting functions. This low
      concentration 1,2-trans beta-selective glycosylation in carbohydrate chemistry
      removes the restriction of using highly reactive thioglycosides to construct 1,2
      trans beta-glycosidic bonds. This is beneficial to the design of new strategies
      for oligosaccharide synthesis, as illustrated in the preparation of the
      biologically relevant beta-(1-->6)-glucan trisaccharide, beta-linked Gb(3) and
      isoGb(3) derivatives.

PMID- 19746472
TI  - Sterically-directed consecutive and size-selective self-assembly of palladium
      diphosphane complexes with an Ar-BIAN ligand: unexpected formation of pentameric
      and hexameric aggregates.
AB  - The coordination properties of N,N'-bis[4-(4
      pyridyl)phenyl]acenaphthenequinonediimine (L(1)) and N,N'-bis[4-(2
      pyridyl)phenyl]acenaphthenequinonediimine (L(2)) were investigated in self
      assembly with palladium diphosphane complexes [Pd(P;P)(H(2)O)(2)](OTf)(2) (OTf =
      triflate) by using various analytical techniques, including multinuclear ((1)H,
      (15)N, and (31)P) NMR spectroscopy and mass spectrometry (P;P = dppp, dppf, dppe;
      dppp = bis(diphenylphosphanyl)propane, dppf = bis(diphenylphosphanyl)ferrocene,
      and dppe = bis(diphenylphosphanyl)ethane). Beside the expected trimeric and
      tetrameric species, the interaction of an equimolar mixture of [Pd(dppp)](2+)
      ions and L(1) also generates pentameric aggregates. Due to the E/Z isomerism of
      L(1), a dimeric product was also observed. In all of these species, which
      correspond to the general formula [Pd(dppp)L(1)](n)(OTf)(2n) (n = 2-5), the L(1)
      ligand is coordinated to the Pd center only through the terminal pyridyl groups.
      Introduction of a second equivalent of the [Pd(dppp)](2+) tecton results in
      coordination to the internal, sterically more encumbered chelating site and
      induces enhancement of the higher nuclearity components. The presence of higher
      order aggregates (n = 5, 6), which were unexpected for the interaction of cis
      protected palladium corners with linear ditopic bridging ligands, has been
      demonstrated both by mass-spectrometric and DOSY NMR spectroscopic analysis. The
      sequential coordination of the [Pd(dppp)](2+) ion is attributed to the dissimilar
      steric properties of the two coordination sites. In the self-assembled species
      formed in a 1:1:1 mixture of [Pd(dppp)](2+)/[Pd(dppe)](2+)/L(1), the sterically
      more demanding [Pd(dppp)](2+) tectons are attached selectively to the pyridyl
      groups, whereas the more hindered imino nitrogen atoms coordinate the less bulky
      dppe complexes, thus resulting in a sterically directed, size-selective sorting
      of the metal tectons. The propensity of the new ligands to incorporate hydrogen
      bonded solvent molecules at the chelating site was confirmed by X-ray diffraction
      studies.

PMID- 19746473
TI  - Single-molecule behavior of dendritic poly(ethylene glycol) structures towards
      lithium ions.

PMID- 19746474
TI  - Propene oxidation with the anionic cluster V(4)O(11) (-): selective epoxidation.

PMID- 19746475
TI  - Bifunctional heterogeneous catalysis of silica-alumina-supported tertiary amines
      with controlled acid-base interactions for efficient 1,4-addition reactions.
AB  - We report the first tunable bifunctional surface of silica-alumina-supported
      tertiary amines (SA-NEt(2)) active for catalytic 1,4-addition reactions of
      nitroalkanes and thiols to electron-deficient alkenes. The 1,4-addition reaction
      of nitroalkanes to electron-deficient alkenes is one of the most useful carbon
      carbon bond-forming reactions and applicable toward a wide range of organic
      syntheses. The reaction between nitroethane and methyl vinyl ketone scarcely
      proceeded with either SA or homogeneous amines, and a mixture of SA and amines
      showed very low catalytic activity. In addition, undesirable side reactions
      occurred in the case of a strong base like sodium ethoxide employed as a
      catalytic reagent. Only the present SA-supported amine (SA-NEt(2)) catalyst
      enabled selective formation of a double-alkylated product without promotions of
      side reactions such as an intramolecular cyclization reaction. The heterogeneous
      SA-NEt(2) catalyst was easily recovered from the reaction mixture by simple
      filtration and reusable with retention of its catalytic activity and selectivity.
      Furthermore, the SA-NEt(2) catalyst system was applicable to the addition
      reaction of other nitroalkanes and thiols to various electron-deficient alkenes.
      The solid-state magic-angle spinning (MAS) NMR spectroscopic analyses, including
      variable-contact-time (13)C cross-polarization (CP)/MAS NMR spectroscopy,
      revealed that acid-base interactions between surface acid sites and immobilized
      amines can be controlled by pretreatment of SA at different temperatures. The
      catalytic activities for these addition reactions were strongly affected by the
      surface acid-base interactions.

PMID- 19746476
TI  - Multi-product classes obtained from allylation of alpha-halo ketones with
      allylzinc bromide.

PMID- 19746477
TI  - Catalytic activity dependency on catalyst components in aerobic copper-TEMPO
      oxidation.
AB  - The influence of catalyst components in the copper-TEMPO (2,2,6,6
      tetramethylpiperidine N-oxide) catalysed aerobic oxidation of alcohols was
      investigated. The type and amount of base greatly influences reactivity. The
      bipyridyl ligand concentration had no major influence on catalysis, but excessive
      amounts led to a decrease in activity for longer reaction times. The kinetic
      dependency for TEMPO was found to be 1.15, and for copper 2.25, which is an
      indication of a binuclear catalytic system. Optimised conditions with various
      allylic and aliphatic alcohols give good to excellent rapid oxidations.

PMID- 19746478
TI  - Biomimetic interaction between Fe(II) and O2: effect of the second coordination
      sphere on O2 binding to Fe(II) complexes: evidence of coordination at the metal
      centre by a dissociative mechanism in the formation of mu-oxo diferric complexes.
AB  - We report that the formation of mu-oxo diferric compounds from O(2) and FeCl(2)
      complexes within the tris(2-pyridylmethyl)amine series (N. K. Thallaj et al.
      Chem. Eur. J., 2008, 14, 6742-6753) involves coordination of O(2) to the metal
      centre and that this reaction occurs following initial dissociation of the bound
      equatorial chloride anion. We also report evidence of the formation of a reduced
      form of dioxygen by an inner-sphere mechanism, thus leading to modification of
      the ligand. The solid-state structures of [FeCl(2)L] complexes (L(1) = mono(alpha
      pivalamidopyridylmethyl)bis(2-pyridylmethyl)amine, L(2) = mono(alpha
      pivalesteropyridylmethyl)bis(2-pyridylmethyl)amine, L(3) = bis(alpha
      pivalamidopyridylmethyl)mono(2-pyridylmethyl)amine are described, and
      spectroscopic data support the structural retention in solution. In
      [FeCl(2)L(3)], the two amide hydrogen atoms stabilise the equatorial chloride
      anion in such a way that its exchange by a weak ligand is impossible:
      [FeCl(2)L(3)] is perfectly oxygen-stable. In [FeCl(2)L(2)], the equatorial
      chloride anion is completely free to move and coordination of O(2) can take
      place. The reaction product with [FeCl(2)L(2)] is a mu-oxo diferric complex in
      which the ester function has been transformed into a phenol group. This
      conversion can be seen as a hydrolysis reaction in basic medium, hence supporting
      the initial formation of a reduced form of dioxygen in the medium. Complex
      [FeCl(2)L(1)] exhibits a very weak reactivity with O(2), in line with a
      semistabilised equatorial chloride counteranion.

PMID- 19746479
TI  - Isoquinolinium salts from o-halobenzaldehydes, amines, and alkynes catalyzed by
      nickel complexes: synthesis and applications.

PMID- 19746480
TI  - Gold-catalyzed intermolecular addition of carbonyl compounds to 1,6-enynes:
      reactivity, scope, and mechanistic aspects.
AB  - A full account of a recently discovered gold(I)-catalyzed reaction, a
      cycloaddition of carbonyl compounds to enynes yielding 2-oxabicyclo[3.1.0]hexanes
      with four stereogenic centers, is presented. The reaction proceeds with very high
      diastereoselectivity. The scope of the reaction has been investigated. In
      addition, experiments and DFT calculations concerning mechanistic aspects were
      carried out. The reaction course varies with the substitution pattern of the
      alkene moiety of the starting enyne. Branched olefins led to 2
      oxabicyclo[3.1.0]hexanes; terminally substituted olefins proceeded with the
      incorporation of two carbonyl components to give
      hexahydrocyclopenta[d][1,3]dioxines.

PMID- 19746481
TI  - Detection and identification of alkylating agents by using a bioinspired
      "chemical nose".
AB  - Alkylating agents are simple and reactive molecules that are commonly used in
      many and diverse fields such as organic synthesis, medicine, and agriculture.
      Some highly reactive alkylating species are also being used as blister chemical
      warfare agents. The detection and identification of alkylating agents is not a
      trivial issue because of their high reactivity and simple structure. Herein, we
      report on a new multispot luminescence-based approach to the detection and
      identification of alkylating agents. In order to demonstrate the potential of the
      approach, seven pi-conjugated oligomers and polymers bearing nucleophilic
      pyridine groups, 1-7, were adsorbed onto a solid support and exposed to vapors of
      alkylators 8-15. The alkylation-induced color-shift patterns of the seven-spot
      array allow clear discrimination of the different alkylators. The spots are
      sensitive to minute concentrations of alkylators and, because the detection is
      based on the formation of new covalent bonds, these spots saturate at about 50
      ppb.

PMID- 19746482
TI  - Stacking structure of confined 1-butanol in SBA-15 investigated by solid-state
      NMR spectroscopy.
AB  - Understanding the complex thermodynamic behavior of confined amphiphilic
      molecules in biological or mesoporous hosts requires detailed knowledge of the
      stacking structures. Here, we present detailed solid-state NMR spectroscopic
      investigations on 1-butanol molecules confined in the hydrophilic mesoporous SBA
      15 host. A range of NMR spectroscopic measurements comprising of (1)H spin
      lattice (T(1)), spin-spin (T(2)) relaxation, (13)C cross-polarization (CP), and
      (1)H,(1)H two-dimensional nuclear Overhauser enhancement spectroscopy ((1)H,(1)H
      2D NOESY) with the magic angle spinning (MAS) technique as well as static wide
      line (2)H NMR spectra have been used to investigate the dynamics and to observe
      the stacking structure of confined 1-butanol in SBA-15. The results suggest that
      not only the molecular reorientation but also the exchange motions of confined
      molecules of 1-butanol are extremely restricted in the confined space of the SBA
      15 pores. The dynamics of the confined molecules of 1-butanol imply that the
      (1)H,(1)H 2D NOESY should be an appropriate technique to observe the stacking
      structure of confined amphiphilc molecules. This study is the first to observe
      that a significant part of confined 1-butanol molecules are orientated as tilted
      bilayered structures on the surface of the host SBA-15 pores in a time-average
      state by solid-state NMR spectroscopy with the (1)H,(1)H 2D NOESY technique.

PMID- 19746483
TI  - Theoretical insights on methylbenzene side-chain growth in ZSM-5 zeolites for
      methanol-to-olefin conversion.
AB  - The key step in the conversion of methane to polyolefins is the catalytic
      conversion of methanol to light olefins. The most recent formulations of a
      reaction mechanism for this process are based on the idea of a complex
      hydrocarbon-pool network, in which certain organic species in the zeolite pores
      are methylated and from which light olefins are eliminated. Two major mechanisms
      have been proposed to date-the paring mechanism and the side-chain mechanism
      recently joined by a third, the alkene mechanism. Recently we succeeded in
      simulating a full catalytic cycle for the first of these in ZSM-5, with inclusion
      of the zeolite framework and contents. In this paper, we will investigate crucial
      reaction steps of the second proposal (the side-chain route) using both small and
      large zeolite cluster models of ZSM-5. The deprotonation step, which forms an
      exocyclic double bond, depends crucially on the number and positioning of the
      other methyl groups but also on steric effects that are typical for the zeolite
      lattice. Because of steric considerations, we find exocyclic bond formation in
      the ortho position to the geminal methyl group to be more favourable than
      exocyclic bond formation in the para position. The side-chain growth proceeds
      relatively easily but the major bottleneck is identified as subsequent de
      alkylation to produce ethene. These results suggest that the current formulation
      of the side-chain route in ZSM-5 may actually be a deactivating route to coke
      precursors rather than an active ethene-producing hydrocarbon-pool route. Other
      routes may be operating in alternative zeotype materials like the silico
      aluminophosphate SAPO-34.

PMID- 19746484
TI  - Expeditious synthesis of hippuristanol and congeners with potent
      antiproliferative activities.

PMID- 19746485
TI  - The influence of N-heterocyclic carbenes (NHC) on the reactivity of
      [Ru(NHC)(4)H](+) with H(2), N(2), CO and O(2).
AB  - The five-coordinate ruthenium N-heterocyclic carbene (NHC) hydrido complexes
      [Ru(IiPr(2)Me(2))(4)H][BAr(F) (4)] (1; IiPr(2)Me(2)=1,3-diisopropyl-4,5
      dimethylimidazol-2-ylidene; Ar(F)=3,5-(CF(3))(2)C(6)H(3)),
      [Ru(IEt(2)Me(2))(4)H][BAr(F) (4)] (2; IEt(2)Me(2)=1,3-diethyl-4,5
      dimethylimidazol-2-ylidene) and [Ru(IMe(4))(4)H][BAr(F) (4)] (3; IMe(4)=1,3,4,5
      tetramethylimidazol-2-ylidene) have been synthesised following reaction of
      [Ru(PPh(3))(3)HCl] with 4-8 equivalents of the free carbenes at ambient
      temperature. Complexes 1-3 have been structurally characterised and show square
      pyramidal geometries with apical hydride ligands. In both dichloromethane or
      pyridine solution, 1 and 2 display very low frequency hydride signals at about
      delta -41. The tetramethyl carbene complex 3 exhibits a similar chemical shift in
      toluene, but shows a higher frequency signal in acetonitrile arising from the
      solvent adduct [Ru(IMe(4))(4)(MeCN)H][BAr(F) (4)], 4. The reactivity of 1-3
      towards H(2) and N(2) depends on the size of the N-substituent of the NHC ligand.
      Thus, 1 is unreactive towards both gases, 2 reacts with both H(2) and N(2) only
      at low temperature and incompletely, while 3 affords [Ru(IMe(4))(4)(eta(2)
      H(2))H][BAr(F) (4)] (7) and [Ru(IMe(4))(4)(N(2))H][BAr(F) (4)] (8) in
      quantitative yield at room temperature. CO shows no selectivity, reacting with 1
      3 to give [Ru(NHC)(4)(CO)H][BAr(F) (4)] (9-11). Addition of O(2) to solutions of
      2 and 3 leads to rapid oxidation, from which the Ru(III) species
      [Ru(NHC)(4)(OH)(2)][BAr(F) (4)] and the Ru(IV) oxo chlorido complex
      [Ru(IEt(2)Me(2))(4)(O)Cl][BAr(F) (4)] were isolated. DFT calculations reproduce
      the greater ability of 3 to bind small molecules and show relative binding
      strengths that follow the trend CO >> O(2) > N(2) > H(2).

PMID- 19746486
TI  - Synthesis, X-ray structure of ferrocene bearing bis(Zn-cyclen) complexes and the
      selective electrochemical sensing of TpT.
AB  - The new ligand, [Fc(cyclen)(2)] (5) (Fc=ferrocene, cyclen=1,4,7,10
      tetraazacyclododecane), and corresponding Zn(II) complex receptor,
      [Fc{Zn(cyclen)(CH(3)OH)}(2)](ClO(4))(4) (1), consisting of a ferrocene moiety
      bearing one Zn(II)-cyclen complex on each cyclopentadienyl ring, have been
      designed and prepared through a multi-step synthesis. Significant shifts in the
      (1)H NMR signals of the ferrocenyl group, cf. ferrocene and a previously reported
      [Fc{Zn(cyclen)}](2+) derivative, indicated that the two Zn(II)-cyclen units in 1
      significantly affect the electronic properties of the cyclopentadienyl rings. The
      X-ray crystal structure shows that the two positively charged Zn(II)-cyclen
      complexes are arranged in a trans like configuration, with respect to the
      ferrocene bridging unit, presumably to minimise electrostatic repulsion. Both 5
      and 1 can be oxidized in 1:4 CH(2)Cl(2)/CH(3)CN and Tris-HCl aqueous buffer
      solution under conditions of cyclic voltammetry to give a well defined ferrocene
      centred (Fc(0/+)) process. Importantly, 1 is a highly selective electrochemical
      sensor of thymidilyl(3'-5')thymidine (TpT) relative to other nucleobases and
      nucleotides in Tris-HCl buffer solution (pH 7.4). The electrochemical
      selectivity, detected as a shift in reversible potential of the Fc(0/+)
      component, is postulated to result from a change in the configuration of
      bis(Zn(II)-cyclen) units from a trans to a cis state. This is caused by the
      strong 1:1 binding of the two deprotonated thymine groups in TpT to different
      Zn(II) centres of receptor 1. UV-visible spectrophotometric titrations confirmed
      the 1:1 stoichiometry for the 1:TpT adduct and allowed the determination of the
      apparent formation constant of 0.89+/-0.10x10(6) M(-1) at pH 7.4.

PMID- 19746487
TI  - Sc(III)-doped zeolites as new heterogeneous catalysts: mukaiyama aldol reaction.
AB  - Sc(III)-doped solids based on zeolite materials have been investigated for the
      first time as catalysts in organic synthesis. Sc(III)-USY zeolite proved to be a
      novel and very efficient heterogeneous catalyst for the Mukaiyama aldol reaction.
      This easy-to-prepare catalyst exhibited wide scope and compatibility with
      functional groups and is very simple to use, easy to remove (by simple
      filtration), and is recyclable (up to three times without loss of activity).

PMID- 19746488
TI  - Structural tracking of the potassium-mediated magnesiation of anisole.

PMID- 19746489
TI  - Stereoselective synthesis of bicyclic nitrocyclopropanes by a radical-anion
      domino reaction.

PMID- 19746490
TI  - Molecular and supramolecular networks on surfaces: from two-dimensional crystal
      engineering to reactivity.
AB  - The invention of the scanning tunneling microscope has led to the visualization
      of molecules in real space on atomically flat conductive substrates. This has
      boosted research into supramolecular chemistry on surfaces. In this Review, we
      highlight recent developments in the design and functionality of supramolecular
      surface patterns, with special attention paid to those networks which are chiral
      or contain a high degree of porosity as well as to the reactivity, which is one
      of the most important recent developments in supramolecular surface chemistry.

PMID- 19746491
TI  - Multiplexed analysis of Hg2+ and Ag+ ions by nucleic acid functionalized CdSe/ZnS
      quantum dots and their use for logic gate operations.

PMID- 19746492
TI  - Secondary-structure-inducible ligand fluorescence coupled with PCR.

PMID- 19746493
TI  - Constitutional adaptation of dynamic polymers: hydrophobically driven sequence
      selection in dynamic covalent polyacylhydrazones.

PMID- 19746494
TI  - Structural basis and stereochemistry of triscatecholate siderophore binding by
      FeuA.

PMID- 19746495
TI  - Parallel isotope-based quantification of modified tRNA nucleosides.

PMID- 19746496
TI  - Cyclic self-assembled structures of chlorophyll dyes on HOPG by the dendron wedge
      effect.

PMID- 19746497
TI  - Gas-phase synthesis and intense visible absorption of tryptophan-gold cations.

PMID- 19746498
TI  - Construction of two vicinal quaternary carbons by asymmetric allylic alkylation:
      total synthesis of hyperolactone C and (-)-biyouyanagin A.

PMID- 19746499
TI  - Consecutive C-H functionalization reactions of arenes: synthesis of carbo- and
      heteropolycyclic skeletons.

PMID- 19746500
TI  - Synthesis and characterization of digerma-closo-dodecaborate: a higher homologue
      of icosahedral ortho-carborane.

PMID- 19746501
TI  - Directed evolution of orthogonal ligand specificity in a single scaffold.

PMID- 19746503
TI  - Flipping marvelous: new zeolites by new methods.

PMID- 19746502
TI  - Total syntheses of (+)-haplophytine.

PMID- 19746504
TI  - Macroscopic properties of phospholipid vesicles with a contact angle between the
      membrane domains.
AB  - Ternary mixtures of a high-melting lipid, a low-melting lipid, and cholesterol
      are known to form domains of a liquid-ordered and a liquid-disordered phase in
      bilayer membranes. We prepare giant vesicles from a
      sphingomyelin/dioleoylphosphocholine/cholesterol mixture and then examine them
      using fluorescence microscopy. NBD-labeled lipid and BODIPY-labeled cholesterol
      are used to identify the phase domains of the membrane. A vesicle with only two
      domains, one in a liquid-ordered and one in a liquid-disordered phase, is chosen
      because of its simple geometry, for convenient comparison of the experimental
      results with the theoretical predictions. A microinjector is used to gradually
      decrease and/or increase the volume of the vesicles by changing the osmolarity of
      the sugar solution. The relevant energy terms of the membrane mechanics are the
      elastic energies of the domains and the energy of the domain boundary. The
      elastic energy of the membrane domains can be described by two terms: the bending
      energy and the Gaussian bending energy. The energy of the domain boundary is
      proportional to its length. At the boundary between the domains a contact angle
      is taken into consideration. Then, in order to obtain values for the lateral
      tension and the contact angle, the areas of the domains and the characteristic
      dimensions of the shape are determined for different volumes. The best fits were
      obtained for a line tension of 6+/-3 pN and a contact angle of 1.4+/-0.3 rad.

PMID- 19746505
TI  - Designing the folding mechanics of coiled coils.
AB  - Naturally occurring coiled coils are often not homogeneous throughout their
      entire structure but rather interrupted by sequence discontinuities and non
      coiled-coil-forming subsegments. We apply atomic force microscopy to locally
      probe the mechanical folding/unfolding process of a well-understood model coiled
      coil when unstructured subsegments with different sizes are added. We find that
      the refolding force decreases from 7.8 pN with increasing size of the added
      unstructured subsegment, while the unfolding properties of the model coiled coil
      remain unchanged. We show that this behavior results from the increased size of
      the nucleation seed which has to form before further coiled-coil folding can
      proceed. Since the nucleation seed size is linked to the width of the energetic
      folding barrier, we are able to directly measure the dependence of folding forces
      on the barrier width. Our results allow the design of coiled coils with
      designated refolding forces by simply adjusting the nucleation seed size.

PMID- 19746506
TI  - Steady light from quantum dots, at last. But how?

PMID- 19746507
TI  - Reduction of transition-metal-coordinated carbon monoxide by a rare-earth hydride
      cluster: isolation of well-defined heteromultimetallic oxycarbene, oxymethyl,
      carbene, and methyl complexes.

PMID- 19746508
TI  - Syringolin A selectively labels the 20 S proteasome in murine EL4 and wild-type
      and bortezomib-adapted leukaemic cell lines.
AB  - The natural product syringolin A (SylA) is a potent proteasome inhibitor with
      promising anticancer activities. To further investigate its potential as a lead
      structure, selectivity profiling with cell lysates was performed. At therapeutic
      concentrations, a rhodamine-tagged SylA derivative selectively bound to the 20 S
      proteasome active sites without detectable off-target labelling. Additional
      profiling with lysates of wild-type and bortezomib-adapted leukaemic cell lines
      demonstrated the retention of this proteasome target and subsite selectivity as
      well as potency even in clinically relevant cell lines. Our studies, therefore,
      propose that further development of SylA might indeed result in an improved small
      molecule for the treatment of leukaemia.

PMID- 19746509
TI  - Direct oxidation of beta-aryl substituted aldehydes to alpha,beta-unsaturated
      aldehydes promoted by an o-anisidine-Pd(OAc)2 co-catalyst.
AB  - An o-anisidine-Pd(OAc)2 catalytic system for the direct co-catalytic Saegusa
      oxidation of beta-aryl substituted aldehydes to alpha,beta-unsaturated aldehydes
      has been developed. The use of o-anisidine in place of (S)-diphenylprolinol made
      the process more simply and cost-effective. The process not only features the use
      of unmodified aldehydes rather than enol silyl ethers, but also gives moderate to
      good yields (44-72%).

PMID- 19746510
TI  - Organocatalytic enantioselective cross-aldol reactions of aldehydes with isatins:
      formation of two contiguous quaternary centered 3-substituted 3-hydroxyindol-2
      ones.

PMID- 19746511
TI  - Genetic testing may be newest long-term heart risk predictor. The 61-year-old
      Framingham method may be surpassed by a new gold standard.

PMID- 19746512
TI  - Increase your brain processing speed and improve your memory.  Exercises aimed at
      fine-tuning brain function can boost memory as well.

PMID- 19746514
TI  - New option for wrist arthritis surgery.  A modified approach to an existing
      procedure improves cartilage status for wrist reconstruction.

PMID- 19746513
TI  - 3 steps to stroke prevention and stroke recovery.  Drink tea, take statins, and
      change negative lifestyle habits--even just one--to aid stroke risk reduction and
      recovery.

PMID- 19746515
TI  - Revised view of prophylactic mastectomy.  Recent findings put risk and options
      into better perspective, and may help women decide in favor of other therapies.

PMID- 19746516
TI  - I had a mild stroke two years ago, but recovered completely and am now healthy
      and active.  After my stroke, my doctor prescribed a statin medication, even
      though I don't have heart disease.  The medication gives me indigestion.  Can I
      stop it without any problems?

PMID- 19746517
TI  - Can air pollution cause heart disease?  If so, how can I reduce my risk?

PMID- 19746518
TI  - I've been diagnosed with gout and told that the elevated level of uric acid that
      brought it about may also increase my risk of heart attack. Is this true?

PMID- 19746519
TI  - I've just been diagnosed with "muscular rheumatism."  Is this a form of
      arthritis?

PMID- 19746520
TI  - US joins China in climate talks.

PMID- 19746521
TI  - Regulation of drug resistance by human pregnane X receptor in breast cancer.
AB  - Drug resistance is a significant barrier to an effective treatment of breast
      cancer. Human pregnane X receptor (hPXR), an orphan nuclear receptor known for
      its activation by many important clinical drugs, is a major transcription factor
      of drug metabolism enzymes (DMEs), such as cytochrome P450 3A4 (CYP3A4), and
      efflux transporters such as multi-drug resistance gene (MDR1). hPXR has been
      detected in human breast cancers but its role in responses of cancers toward
      drugs remains unknown. In this study, hPXR expression was confirmed in breast
      cancer cell lines and in normal and cancerous human breast specimens.
      Preactivation of hPXR by SR12813 in MDA-MB-231 cells led to an increased
      resistance to Taxol at concentrations of 20 and 50 nmol/L. A significant increase
      in resistance toward tamoxifen was also observed in MCF-7 with hPXR
      preactivation. Activation of hPXR led to an increased expression of CYP3A4 and
      MDR1, two possible mediators for hPXR-mediated drug resistance in breast cancers.
      Furthermore, knockdown of hPXR via small hairpin RNA (shRNA) sensitized MDA-MB
      231 and MCF-7 cells to the treatment of Taxol, vinblastine or tamoxifen. The
      reduction in resistance of hPXR knockdown cells was further confirmed by reduced
      colony formation under the pressure of cancer treatment drugs. Taken together,
      our data suggest a potential role of hPXR in breast cancer resistance to drug
      treatments.

PMID- 19746522
TI  - The results support the use of atorvastatin in elderly patients with recent
      stroke or TIA.

PMID- 19746523
TI  - Analysis of SPARCL trial data for reduction of future stroke risk in older stroke
      patients with recent stroke or TIA.

PMID- 19746524
TI  - [Proceedings of the Annual Conference of the German Society for Rheumatology.
      September 23-26, 2009. Cologne, Germany].

PMID- 19746525
TI  - Gemcitabine: new indication. Relapsed ovarian cancer: simply more toxic.
      Increases haematologic toxicity but not overall survival.

PMID- 19746526
TI  - Bevacizumab + sunitinib: microangiopathic haemolytic anaemia. A serious drug
      interaction between 2 cancer drugs.

PMID- 19746527
TI  - Imiquimod: liver damage: topical use, systemic effects.

PMID- 19746528
TI  - Dextropropoxyphene: withdrawn in the EU. Withdrawn from pharmacies in France.

PMID- 19746529
TI  - Dextropropoxyphene: withdrawal from the US market requested: harmful drug.

PMID- 19746530
TI  - Mefloquine: interstitial pneumonia: rare events.

PMID- 19746531
TI  - Memantine: heart failure: harmful drug.

PMID- 19746532
TI  - Erlotinib: potentially fatal in cases of liver failure: a contraindication.

PMID- 19746533
TI  - Immunosuppressants: JC virus encephalopathy. Rare but fatal.

PMID- 19746534
TI  - Patent blue V: anaphylaxis. Reactions after sentinel lymph node identification.

PMID- 19746535
TI  - Dishing the dirt on MRSA.

PMID- 19746536
TI  - Dishing the dirt on MRSA.

PMID- 19746537
TI  - Treatments for MRSA.

PMID- 19746538
TI  - Sugar swings, Mary Poppins, Pop-Tarts & more.

PMID- 19746539
TI  - Will you stay with me?

PMID- 19746540
TI  - Disabled nurses discover new career paths.

PMID- 19746541
TI  - Awareness of breast cancer in men.

PMID- 19746542
TI  - The need to keep up the pressure for change.

PMID- 19746543
TI  - Disciplinary tactics.

PMID- 19746545
TI  - Scotland the brave.

PMID- 19746544
TI  - A question of balance.

PMID- 19746546
TI  - Government proposals to regulate the psychotherapies under the Health Professions
      Council (HPC).

PMID- 19746547
TI  - Case law is the gold standard for benefit appeals.

PMID- 19746548
TI  - The recession? Neither the Queen--nor Chris Flitch--is amused.

PMID- 19746549
TI  - Cashing in on top tips for talking about debt.

PMID- 19746550
TI  - Banking on the mad effects of debt.

PMID- 19746551
TI  - The bigger User-led organisations can play a huge role in promoting the
      personalisation agenda.

PMID- 19746552
TI  - The development of a mental health service within a youth offending team.
AB  - Positive performance indicators suggest that young offenders who have previously
      been reluctant to engage with a generic child and adolescent mental health
      service are engaging with this service. Additionally, collaborative working
      between agencies dedicated to meeting the needs of this client group has
      increased. These outcomes ultimately increase the scope for this group to have
      their needs addressed in a comprehensive way.

PMID- 19746553
TI  - Mind inside.

PMID- 19746554
TI  - Back on trax.

PMID- 19746555
TI  - Is it right to exclude people with a mental illness from jury service?

PMID- 19746556
TI  - Network.

PMID- 19746557
TI  - Viewpoint.

PMID- 19746558
TI  - On the record. Interview by Alita Howe.

PMID- 19746560
TI  - Fifty years of Landau-Kleffner syndrome. Proceedings of an international
      symposium. November 2-4, 2007. Alden-Biesen, Belgium.

PMID- 19746559
TI  - Ethical advertising in dentistry.

PMID- 19746561
TI  - Fibromyalgia: poorly understood; treatments are disappointing.
AB  - (1) Fibromyalgia is characterised by a range of symptoms that include muscle
      pain, fatigue and sleep disorders. Anxiety and depression are often also present.
      The cause is unknown. More women than men are affected; (2) The following review
      focuses on differential diagnoses and available treatments for fibromyalgia,
      based on a review of the literature using the standard Prescrire methodology; (3)
      Fibromyalgia is mainly diagnosed by excluding other possibilities. The principal
      differential diagnoses are rheumatic involvement of the spine, systemic
      inflammatory disorders, and hypothyroidism. Unlike these other conditions,
      fibromyalgia is not associated with radiological or laboratory abnormalities; (4)
      Paracetamol has not been compared with other treatments in fibromyalgia.
      Nonsteroidal antiinflammatory drugs have no specific effect; (5) The only two
      trials assessing tramadol showed little effect; in one study the average pain
      score was 53 mm in the tramadol group versus 65 mm in the placebo group, on a
      scale ranging from 0 to 100 mm. The adverse effects of tramadol are those of
      opiates in general, mainly nausea and dependence. Tramadol interacts with
      numerous other drugs; (6) The efficacy of tricyclic antidepressants is also
      difficult to quantify. Their limited superiority over placebo lasts no more than
      a few months. The efficacy of selective serotonin reuptake inhibitor
      antidepressants (fluoxetine, paroxetine and citalopram), serotonin and
      nonadrenaline reuptake inhibitors (duloxetine and milnacipran) is even less well
      established. Duloxetine has been tested in four placebo-controlled trials with
      unconvincing results; (7) Pregabalin and gabapentin, two antiepileptic drugs,
      appear to be more effective than placebo but have only been tested in short-term
      trials. In one trial 44% of patients in the pregabalin group said they felt
      better after 13 weeks versus 35% of patients in the placebo group. However,
      adverse effects are frequent and sometimes troublesome (drowsiness, dizziness,
      nausea, weight gain). In clinical trials, 19% to 33% of patients stopped
      treatment due to adverse effects after 13 weeks, depending on the dose of
      pregabalin; (8) Assessments of non-drug treatments in this setting are generally
      mediocre. The best-assessed alternative therapies (acupuncture and physical
      exercise) only have a limited effect; (9) In practice, when a patient presents
      with symptoms compatible with fibromyalgia, the first step is to rule out a
      treatable condition. Quality of life may be improved by first acknowledging that
      the pain is real, and possibly by providing psychological, medical, social and
      occupational support. The limited efficacy of available drugs, and their
      potential adverse effects, should be discussed with the patient.

PMID- 19746562
TI  - Identifying complications of central venous catheters: infection, thrombosis,
      occlusion.
AB  - (1) The signs of infection of implanted port catheters are inflammation along the
      course of a central catheter, oozing or signs of an abscess of the pocket in
      which the port is implanted. Catheter-related venous thrombosis should be
      suspected in the event of pain, oedema, local swelling, a palpable venous cord
      and development of superficial collateral circulation; (2) The rapid appearance
      of local signs and symptoms at the time of injection suggests extravasation of
      the injected drug; (3) Catheter patency should be checked with normal saline,
      never using too much force if resistance is encountered. If there is a thrombotic
      occlusion, the catheter can often be unblocked with heparin, or if not, with
      urokinase. There is only a moderate risk of bleeding if these agents are used
      carefully.

PMID- 19746563
TI  - Corticosteroids: no drug prevention of fractures needed.
AB  - Long-term corticosteroid therapy increases the risk of fractures, which depends
      on the dose and duration of treatment. No drugs have been demonstrated to reduce
      the incidence of symptomatic fractures in this setting. It is better to keep the
      dose and duration of steroid therapy to the effective minimum, and to choose non
      drug preventive measures.

PMID- 19746564
TI  - Preface. Special issue: Initialization, conceptualization, and application in the
      generalized fractional calculus.

PMID- 19746565
TI  - [Frequency, intensity and need in caries treatment in key age groups of Chechen
      Republic population (Kurchaloev region as an example)].

PMID- 19746566
TI  - Re: Prevalence of intestinal parasites in companion animals in Ontario and
      Quebec, Canada, during the winter months.

PMID- 19746567
TI  - [<<VladMiva>>--proper level of quality and reliability].

PMID- 19746568
TI  - [Aesthetogramma as qualitative appreciation of dentitions visual image].

PMID- 19746569
TI  - [Moscow State Medico-stomatologic University: history, the present,
      perspectives].

PMID- 19746570
TI  - [The Clinic of Ear, Nose and Throat at I.M. Sechenov Moscow Medical Academy: from
      S.F. von Stein until our days].

PMID- 19746571
TI  - Rosuvastatin for cardiovascular prevention: too many uncertainties.
AB  - A randomised trial showed that rosuvastatin had some efficacy in preventing a
      first cardiovascular event, but there was an increased risk of diabetes. The
      article describing this study is too imprecise to recommend the use of
      rosuvastatin in this setting.

PMID- 19746572
TI  - [Anti-inflammatory therapy in the treatment of patients with chronic laryngitis].

PMID- 19746573
TI  - [Traditional approaches to the patient and selected problems of modern
      otorhinolaryngology. Part III].

PMID- 19746574
TI  - [Memoirs of ENT veterans].

PMID- 19746575
TI  - Type 2 diabetes: target HbA1c of about 7%.
AB  - A 17-year follow-up study of patients with type 2 diabetes enrolled in the Ukpds
      trial has shown that glycaemic control targeting HbA1c levels of about 7% is
      associated with lower mortality.

PMID- 19746576
TI  - Promoting breast-feeding: fewer infections than in bottle-fed babies. Very few
      contraindications to breast-feeding.

PMID- 19746577
TI  - Effects of cancer drugs on survival: often poorly evaluated.
AB  - (1) Overall survival is the gold-standard endpoint when evaluating the efficacy
      of cancer drugs; (2) Progression-free survival is an endpoint that combines two
      very different components: death or objective worsening of the tumour. It is a
      heterogeneous endpoint and measurement of the second component is imprecise.
      There are few examples where a correlation has been established between
      progression-free survival and overall survival; (3) Time to progression is an
      endpoint of limited interest: it only takes into account the second component of
      the progression-free survival composite endpoint; (4) Disease-free survival is a
      variant of progression-free survival and is most frequently used for adjuvant
      treatments.

PMID- 19746578
TI  - [12th Statewide Conference on DNA Diagnosis. 24-5 November 2008, Brno].

PMID- 19746579
TI  - Ethnic and racial identity in the brotherhoods of the Rosary of Minas Gerais,
      1700-1830.

PMID- 19746580
TI  - Female apostolates and modernization in mid-nineteenth century Chile.

PMID- 19746581
TI  - Populist anxiety: race and social change in the thought of Romulo Gallegos.

PMID- 19746582
TI  - Tales of two women: the narrative construal of Porfirian reality.

PMID- 19746583
TI  - The "alienated" body: slaves and castas in the Hospital de San Bartolome in Lima,
      1680 to 1700.

PMID- 19746584
TI  - Nineteenth convocation Royal Australasian College of Dental Surgeons conjoint
      with the College of Dental Surgeons of Hong Kong, Hong Kong 2008. Address by the
      President of the Royal Australasian College of Dental Surgeons Neil J J Peppitt,
      BDS, MDSc, FRACDS at the opening ceremony.

PMID- 19746585
TI  - ISHAGE committees--the whole is, indeed, and in deed, greater than the sum of its
      parts.

PMID- 19746586
TI  - Nuclei-size distributions as predictive tools of hematopoietic cell
      proliferation.
AB  - BACKGROUND: Current protocols for transplantation of hematopoietic stem and
      progenitor cells may be limited by donor-cell availability and the long time
      needed to restore neutrophil and platelet counts to normal levels. Ex vivo
      expansion of hematopoietic cells has the potential to decrease the required
      harvest size, and to enhance the transplant outcome, by providing greater numbers
      of progenitor and post-progenitor cells. However, widespread application of ex
      vivo expansion in the clinical setting is complicated by sample-to-sample
      variability in the extent and kinetics of cell expansion. For example, the lag
      time before active cell expansion may vary by several days and some samples may
      never expand under the culture conditions employed. An early determination
      regarding the fate of a culture would save time and resources, and would allow
      corrective action to be taken if desired. Furthermore, anticipation of the onset
      of cell cycling should prove useful in the development of culture-feeding
      strategies, as well as for maximizing transduction efficiency in gene-therapy
      protocols that employ retroviral vectors. METHODS: We demonstrate that the nuclei
      size distribution, which is obtained at the same time as the total nucleated cell
      concentration, can be used to predict the onset of cell proliferation. The
      formation of a second peak (with diameter > 4 microm) in the nuclei-size
      distribution, in addition to the smaller diameter peak (< 4 microm) present for
      quiescent cells, precedes total cell expansion. RESULTS: In particular 94% of all
      MNC and CD34+ cell cultures that we have observed to exhibit a second peak in the
      nuclei-size distribution have realized total cell expansion. Furthermore, only
      one of 67 observed cultures that did not exhibit the formation of a second peak
      realized total cell expansion. The formation of a second peak in the nuclei-size
      distribution is evident, either before or on the same day as the presence of a
      significant fraction of cells in the S-phase of the cell cycle.

PMID- 19746587
TI  - Debulking blood stem cell collections by density gradient centrifugation in a
      closed-vessel system.
AB  - BACKGROUND: Blood stem cells collected by apheresis are largely mononuclear cells
      in nature, so manipulation of blood stem-cell components frequently requires more
      time and reagents than for a marrow harvest. Reducing the nucleated cell number
      in mobilized blood stem-cell collections, while preserving hematopoietic
      progenitor content, would make such manipulations simpler and less costly, but
      only if debulking procedures were not complex. METHODS: We evaluated separation
      of light-density cells and enrichment of CD34+ cells from mobilized peripheral
      blood stem-cell collections by density gradient centrifugation over buoyant
      density solution 60 (BDS 60) in a single, closed vessel. RESULTS: Fifteen
      apheresis products from five normal volunteers and eight cancer patients
      contained 3.44 (range, 1.19-5.51) x 10(10) nucleated cells. Following processing
      and washing, there was a median 29% recovery of nucleated cells, 79% recovery of
      CD34+ cells, 2.49-fold enrichment of CD34+ cells, 0.96-log depletion of CD3+
      cells, 0.48-log depletion of CD56+ cells, and 0.72-log depletion of CD19+ cells.
      Results of processing were affected by the variability in composition of the
      apheresis products. The enrichment of CD34+ cells varied by donor type, and there
      was a logarithmic relationship between the preprocessing percentage of CD19+
      cells and the log reduction in CD19+ cells. Recovery of cells after thawing and
      washing was acceptable for processed cells cryopreserved at concentrations over
      the range of 0.01-1.5 x 10(8)/mL. DISCUSSION: These results demonstrate a simple
      method by which an apheresis product of 1-5 x 10(10) cells can be debulked
      effectively in a single, closed vessel.

PMID- 19746588
TI  - Bi-phasic CD34+ cell mobilization of a syngeneic donor during prolonged G-CSF
      delivery.
AB  - BACKGROUND: G-CSF administration over 10 days and neutrophil cytapheresis have
      been reported in the literature, but the kinetics of CD34+ cells in this
      situation is unclear. CASE: A 42-year-old female underwent syngeneic
      transplantation for metastatic breast cancer. The recipient was in critical
      condition peri-transplant, therefore the donor received G-CSF for 13 days, during
      which eight cytaphereses for both PBPC and neutrophils were performed. Two peaks
      in CD34+ cells were noted; the first on Day 5 and the second on Days 10-13 of G
      CSF administration; a total of 11.6 x 10(6)/kg CD34+ cells and 38.11 x 10(8)/kg
      neutrophils were infused. The recipient's ANC exceeded 0.1 x 10(9)/L on Day +3.
      DISCUSSION: To our knowledge, this is the longest reported cytapheresis of CD34+
      cells from a normal donor The bi-phasic pattern in the cytapheresis product is
      also of interest. It is an unusual pattern that suggests a profound and
      complicated alteration in the marrow progenitor cell pool. If substantiated, this
      finding may offer an alternative cytapheresis schedule for donors.

PMID- 19746589
TI  - Development of an infusible-grade solution for non-cryopreserved hematopoietic
      cell storage.
AB  - BACKGROUND: Various tissue culture medium formulations currently are used to
      transport, store and process stem and progenitor cells for transplantation,
      although these solutions are not manufactured for clinical use. METHODS: We have
      developed an infusible-grade solution, STM-Sav, for short-term liquid cell
      storage and tested its ability to maintain viable functional hematopoietic cells,
      compared with commonly-used tissue culture solutions. G-CSF-stimulated normal
      donor PBPC were stored in alpha-MEM, IMDM, RPMI-1640, AIM 5, X-VIVO 10,
      PlasmaLyte A and STM-Sav, in gas-permeable Cryocyte bags, at ambient temperature
      and 4 degrees C. The percentage of viable cells, percent recovery of viable
      mononuclear cells (MNC), percentage of CD34+ cells, CFU-GM frequency and solution
      pH were determined for each solution, at time points ranging from 0 to 72 h.
      RESULTS: Cells were slightly better maintained at 4 degrees C than at ambient
      temperature. No solution was superior to any other overall, although PlasmaLyte A
      was significantly inferior to all other solutions at preserving viable MNC. STM
      Sav consistently maintained viable, functional cells as well as, or better than
      in-vitro-use-only culture media, or PlasmaLyte A. DISCUSSION: Cells could be
      stored in STM-Sav for at least 24 h at 4 degrees C or ambient temperature, with
      recovery of approximately 90% of initial viable MNC, unchanged percentage CD34+
      cells and stable solution pH.

PMID- 19746590
TI  - Improvement of breast cancer cell detection by immunomagnetic enrichment.
AB  - BACKGROUND: Contaminating breast cancer cells in leukapheresis harvested for
      reinfusion to rebuild hemopoiesis after high-dose therapy have been described by
      several investigators. Methods for tumor cell detection are conventional
      immunocytochemistry, culture techniques and reverse transcriptase PCR. The
      percentage of tumor cell positive leukaphereses shows a wide variation. An
      approach to clarify if these cells can induce systemic relapse is to characterize
      them molecular-genetically and immunologically, but these techniques require a
      sufficient cell count. METHODS: We compared conventional immunocytochemistry with
      immunocytochemistry after immunomagnetic enrichment of cancer cells by HEA-125
      magnetic microbeads for the detection of micrometastatic tumor cells. A total of
      25 samples, consisting of 16 samples from G-CSF-mobilized peripheral stem cell
      harvests, eight BM aspirations and one peripheral blood sample were investigated
      without [median 2, range 1-3 x 10(6) MNCs] and after [median 5, range 1-10 x
      10(7) MNCs] HEA-microbead selection. Additionally 10 buffy coat samples from
      healthy subjects were investigated. RESULTS: Using conventional
      immunocytochemistry, tumor cells could be detected in nine stem cell samples. Two
      BM samples and the blood sample (48%) were positive, with a median tumor cell
      load of 0 (0-12) cells per sample (mean: 2.4). By HEA-bead selection the rate of
      positivity could be increased to 88% (13 stem cell samples, eight marrow samples
      and one blood sample) with a median load of 6 (0-47) (mean 10.6) suspected cells
      (p < 0.007). However, calculation of recovery revealed tumor cell losses by
      immunobead selection. False positive results were not seen. DISCUSSION: We
      conclude first that immunomagnetic selection is an excellent and highly sensitive
      tool to enrich contaminating cancer cells from marrow and stem cell samples;
      second that the existence of real tumor cell negative stem cell harvests is
      doubtful; and third that immunobead selection delivers sufficient tumor cell
      counts for their further characterization by molecular and immunological methods.

PMID- 19746591
TI  - The CD34+ cell concentration in peripheral blood predicts CD34+ cell yield in the
      leukapheresis product.
AB  - BACKGROUND: Measurement of the stem cells collected by leukapheresis has
      undergone marked improvement through the recent advent of CD34 analysis with flow
      cytometry. METHODS: The relationship between CD34+ cell count in the peripheral
      blood (PB) and the leukapheresis product CD34+ cell yield was examined. One
      hundred patients with hematologic and non-hematologic malignancies underwent
      mobilization, with either growth factors combined with chemotherapy, or growth
      factors alone. Prior to each leukapheresis, PB was obtained for measuring the
      WBC, differential and percentage of CD34+ cells. The same tests were then
      performed for the corresponding leukapheresis products and the following
      correlations quantified: PB to product CD34+%, PB to product CD34+ cell
      concentration and PB CD34+ cell concentration, WBC and mononuclear cell (MNC)
      concentration to product CD34+ cell yield/kg. RESULTS: The best predictor of
      product yield of CD34+ cells/kg x 10(6) was the PB CD34+ cell concentration with
      r = 0.93. The resulting regression formula (on log-log scale), log10 yield/kg =
      1.52 + (0.99 x log10 PB CD34+ cell concentration x 10(6)/mL), predicts, with 50%
      probability, a minimally acceptable yield of 0.2 x 10(6) CD34+ cells/kg with a
      CD34+ cell concentration equal to 0.006 CD34+ cells x 10(6)/mL. A cell
      concentration of > or = 0.023 CD34+ cells/mL will ensure that a very high
      fraction (> 97%) of the patient population exceeds the minimally-acceptable
      yield. DISCUSSION: The CD34+ cell concentration measured in the PB prior to
      leukapheresis is an excellent predictor of the yield of CD34+ cells generated in
      the PB stem cell product and should be used to signal the initiation of
      leukapheresis for post-mobilized patients.

PMID- 19746592
TI  - Quantitation of the proliferative potential of highly enriched human primitive
      hematopoietic progenitor cells using a stroma-free limiting dilution assay with
      automated scoring.
AB  - BACKGROUND: Increasing use of phenotypically-enriched stem cell populations for
      clinical hematopoietic transplants has led to an urgent demand for a reliable,
      rapid and simple functional assay which would provide an estimation of the
      reconstituting potential of cells prior to transplantation. METHODS: We have
      developed a 2-week quantitative, stroma-free assay to measure the frequency of
      primitive progenitors within hematopoietic cell samples. This relatively short
      term assay provides frequency information which correlates with that measured by
      a 5-week stroma-dependent CAFC assay. Cells with the phenotype CD34+Thy-1+ were
      purified by fluorescence-activated cell sorting from peripheral blood apheresis
      products of multiple myeloma patients mobilized with cytoxan and GM-CSF. CD34+Thy
      1+ cells were plated at limiting dilution into microtiter wells and cultured in
      an Iscove's based serum-deprived culture medium, supplemented with the cytokines,
      interleukin (IL)-3, IL-6, G-CSF, Flk2/Flt3 ligand (FL) and Kit ligand (KL). After
      2 weeks, cell proliferation in individual wells was quantified by microscopy and
      bright-field imaging, or by using a fluorescent nucleic acid-binding dye and
      fluorimetry. Poisson statistics were used to calculate the frequency of wells
      containing cells with high proliferative potential (wells containing > or = 500
      cells). RESULTS: Progenitor cell frequencies generated using this assay were
      compared by linear regression analysis to those generated from 32 parallel CAFC
      and CFU-C assays performed on the same patient samples. Correlations were r =
      0.80, r2 = 0.65, and r = 0.76, r2 = 0.58, respectively; these correlations were
      highly significant (p < 10(-7)). DISCUSSION: This limiting dilution assay should
      more directly quantitate the potential of primitive hematopoietic cells than a
      CFU-C assay. It also has advantages over both the CAFC and the CFU-C assay, in
      that scoring has been automated, making it simple, rapid, and objective compared
      with manual cobblestone area or colony counting. The described limiting dilution
      assay may provide a useful alternative to assays currently used to evaluate the
      viability and proliferative potential of purified hematopoietic cells intended
      for transplant.

PMID- 19746593
TI  - FDA wrokshop summary: FDA-NCI workshop on tumor vaccines.

PMID- 19746594
TI  - Asymmetric hydrogenations (Nobel lecture).
AB  - The start of the development of catalysts for asymmetric hydrogenation was the
      concept of replacing the triphenylphosphane ligand of the Wilkinson catalyst with
      a chiral ligand. With the new catalysts, it should be possible to hydrogenate
      prochiral olefins. Knowles and his co-workers were convinced that the phosphorus
      atom played a central role in this selectivity, as only chiral phosphorus ligands
      such as (R,R)-DIPAMP, whose stereogenic center lies directly on the phosphorus
      atom, lead to high enantiomeric excesses when used as catalysts in asymmetric
      hydrogenation reactions. This hypothesis was disproven by the development of
      ligands with chiral carbon backbones. Although the exact mechanism of action of
      the phosphane ligands is not incontrovertibly determined to this day, they
      provide a simple entry to a large number of chiral compounds.

PMID- 19746595
TI  - Asymmetric catalysis: science and opportunities (Nobel lecture).
AB  - Asymmetric catalysis, in its infancy in the 1960s, has dramatically changed the
      procedures of chemical synthesis, and resulted in an impressive progression to a
      level that technically approximates or sometimes even exceeds that of natural
      biological processes. The recent exceptional advances in this area attest to a
      range of conceptual breakthroughs in chemical sciences in general, and to the
      practical benefits of organic synthesis, not only in laboratories but also in
      industry. The growth of this core technology has given rise to enormous economic
      potential in the manufacture of pharmaceuticals, animal health products,
      agrochemicals, fungicides, pheromones, flavors, and fragrances. Practical
      asymmetric catalysis is of growing importance to a sustainable modern society, in
      which environmental protection is of increasing concern. This subject is an
      essential component of molecular science and technology in the 21st century. Most
      importantly, recent progress has spurred various interdisciplinary research
      efforts directed toward the creation of molecularly engineered novel functions.
      The origin and progress of my research in this field are discussed.

PMID- 19746596
TI  - Searching for new reactivity (Nobel lecture).
AB  - The processes for the selective oxidation of olefins have long been among the
      most useful tools for day-to-day organic synthesis. Herein, the focus is on the
      asymmetric-epoxidation (AE) and asymmetric-dihydroxylation (AD) reactions
      developed by Sharpless and co-workers. The reactions have a wide scope, are
      simple to run, and involve readily available starting materials. Ligand
      accelerated catalysis is crucial to these reactions and might be the agent for
      uncovering more catalytic processes. In addition to the selectivity benefits of
      catalysis, the phenomenon of turnover (amplification) raises its potential
      impact. The author and his co-workers developed small, highly enantioselective
      catalysts that were unfettered by the "lock-and-key" selectivity of Natures
      enzymes, and tolerant of substrates throughout the entire range of olefin
      substitution patterns.

PMID- 19746597
TI  - Shape-memory polymers.
AB  - Material scientists predict a prominent role in the future for self-repairing and
      intelligent materials. Throughout the last few years, this concept has found
      growing interest as a result of the rise of a new class of polymers. These so
      called shape-memory polymers by far surpass well-known metallic shape-memory
      alloys in their shape-memory properties. As a consequence of the relatively easy
      manufacture and programming of shape-memory polymers, these materials represent a
      cheap and efficient alternative to well-established shape-memory alloys. In shape
      memory polymers, the consequences of an intended or accidental deformation caused
      by an external force can be ironed out by heating the material above a defined
      transition temperature. This effect can be achieved because of the given
      flexibility of the polymer chains. When the importance of polymeric materials in
      our daily life is taken into consideration, we find a very broad, additional
      spectrum of possible applications for intelligent polymers that covers an area
      from minimally invasive surgery, through high-performance textiles, up to self
      repairing plastic components in every kind of transportation vehicles.

PMID- 19746598
TI  - An omnivorous curiosity, a sense of wonder, and a taste for the spectacular.

PMID- 19746599
TI  - Patterning of a colloidal crystal film on a modified hydrophilic and hydrophobic
      surface.

PMID- 19746600
TI  - An inverted metal-organic framework with compartmentalized cavities constructed
      by using an organic bridging unit derived from the solid state.

PMID- 19746601
TI  - Enhanced luminescence and photomagnetic properties of surface-modified EuO
      nanocrystals.

PMID- 19746602
TI  - Zinc(II) slides on a ligand surface: the X-ray crystal structure and dynamic
      behavior in solution of [Zn(H2L)(tacn)].

PMID- 19746603
TI  - Charge-density study of methane di(triimido)sulfonic acid H2C(S[(NtBu),(NHtbu)]2-
      the NR analogue of H2C[s(O)2(OH)]2.

PMID- 19746604
TI  - Structural dependence of redox-induced dimerization as studied by in situ
      ESR/UV/Vis-NIR spectroelectrochemistry: the fluoranthenopyracylene oligomers.

PMID- 19746605
TI  - Synthesis and stereoselective self-assembly of double- and triple-stranded
      helicates.

PMID- 19746606
TI  - Traube's "oxazomalonic acid" is a 3-hydroxysydnone carboxylate with an E-ONNO
      geometry.

PMID- 19746607
TI  - Orbital interactions in strong and weak hydrogen bonds are essential for DNA
      replication.

PMID- 19746608
TI  - [[Li(thf)3]2Ga2[As(SiiPr3)]4]--a compound with gallium-arsenic double bonds.

PMID- 19746609
TI  - Total synthesis of woodrosin I.

PMID- 19746610
TI  - Model studies towards azadirachtin: part 1. Construction of the crowded C8-C14
      bond by radical chemistry.

PMID- 19746611
TI  - Model studies towards azadirachtin: part 2. Construction of the crowded C8-C14
      bond by transition metal chemistry.

PMID- 19746612
TI  - A click chemistry approach to tetrazoles by Huisgen 1,3-dipolar cycloaddition:
      synthesis of 5-sulfonyl tetrazoles from azides and sulfonyl cyanides.

PMID- 19746613
TI  - A click chemistry approach to tetrazoles by Huisgen 1,3-dipolar cycloaddition:
      synthesis of 5-acyltetrazoles from azides and acyl cyanides.

PMID- 19746614
TI  - Controlled hierarchical self-assembly and deposition of nanoscale photonic
      materials.

PMID- 19746615
TI  - Identification of Jahn-Teller effects in both singlet and triplet low-energy
      states of [(eta6-benzene)Nb(CO)3]+.

PMID- 19746616
TI  - Remarkable boosting of the binding of ion-paired organic salts by binary host
      systems.

PMID- 19746617
TI  - The [closo-2-CB6H7](-) ion: the first representative of the 7-vertex
      monocarbaborane series.

PMID- 19746618
TI  - Conformational locking of the glycosyl acceptor for stereocontrol in the key step
      in the synthesis of heparin.

PMID- 19746619
TI  - The effect of a hydroxy protecting group on the PtCl2-catalyzed cyclization of
      dienynes--a novel, efficient, and selective synthesis of carbocycles.

PMID- 19746620
TI  - Dioxygen activation by a mononuclear IrII-ethene complex.

PMID- 19746621
TI  - A highly regioselective synthesis of polysubstituted naphthalene derivatives
      through gallium trichloride catalyzed alkyne--aldehyde coupling.

PMID- 19746622
TI  - A new protocol for the enantioselective synthesis of methyl-substituted alkanols
      and their derivatives through a hydroalumination/ zirconium-catalyzed
      alkylalumination tandem process.

PMID- 19746623
TI  - A synthetic approach towards the C1-C9 subunit of zincophorin.

PMID- 19746624
TI  - Efficient and selective hydroacylation of 1-alkynes with aldehydes by a chelation
      assisted catalytic system.

PMID- 19746625
TI  - A tetranuclear mixed-valent Mn(II)3Mn(IV) compound with a (mu4-O)Mn4 core.

PMID- 19746626
TI  - Nucleation of MCM-41 nanoparticles by internal reorganization of disordered and
      nematic-like silica-surfactant clusters.

PMID- 19746627
TI  - Vesicular nanostructures prepared by reactive melt blending.

PMID- 19746628
TI  - Enantioselective photochromic reaction of a [2.2]metacyclophan-1-ene.

PMID- 19746629
TI  - Cyclization of (-)-pregaliellalactone in the fungus Galiella rufa.

PMID- 19746630
TI  - Diastereoselective synthesis of trans-1,2-dialkylcyclopropanols by the
      Kulinkovich hydroxycyclopropanation of homoallylic alcohols.

PMID- 19746631
TI  - Morphosynthesis of octacalcium phosphate hollow microspheres by polyelectrolyte
      mediated crystallization.

PMID- 19746632
TI  - Structural characterization of a cationic zirconocene olefin polymerization
      catalyst with its methylated boralumoxane counterion.

PMID- 19746633
TI  - BuMgNiPr2: a new base for stoichiometric, position-selective deprotonation of
      cyclopropane carboxamides and other weak CH acids.

PMID- 19746634
TI  - New methods for proteomic research: preparation of proteins with N-terminal
      cysteines for labeling and conjugation.

PMID- 19746635
TI  - Icosahedral WAu12: a predicted closed-shell species, stabilized by aurophilic
      attraction and relativity and in accord with the 18-electron rule.

PMID- 19746636
TI  - Naked-eye sensitive detection of immunoglubulin G by enlargement of Au
      nanoparticles in vitro.

PMID- 19746637
TI  - Ligand topology tuning of iron-catalyzed hydrocarbon oxidations.

PMID- 19746638
TI  - Design of a bilayer structure in an organic inclusion compound.

PMID- 19746639
TI  - Synthesis of the functionalized tricyclic skeleton of guanacastepene A: a tandem
      epoxide-opening beta-elimination/knoevenagel cyclization.

PMID- 19746640
TI  - A stereoselective route to guanacastepene A through a surprising epoxidation.

PMID- 19746641
TI  - Methyleneimine CH2=NH as a unidentate ligand in rhenium complexes.

PMID- 19746642
TI  - Total synthesis of the amaryllidaceae alkaloid (+)-plicamine and its unnatural
      enantiomer by using solid-supported reagents and scavengers in a multistep
      sequence of reactions.

PMID- 19746643
TI  - Catalytic enantioselective synthesis of beta3-amino acids.

PMID- 19746644
TI  - Purity and recovery of the CD34+ cell fraction, obtained by the CEPRATE selection
      system from PBSC collections, can be augmented by meticulous washing steps.

PMID- 19746645
TI  - Influence of T cell depletion method on circulating gammadelta T cell
      reconstitution and potential role in the graft-versus-leukemia effect.
AB  - BACKGROUND: Our laboratory previously reported that leukemia patients who
      developed > or = 10% gammadelta+ T cells during the first six months after
      receiving an anti-TCRalphabeta T-cell-depleted (TCD) graft from a partially
      mismatched related donor (PMRD) had a disease-free survival (DFS) advantage.
      These gammadelta+ T cells were V81+CD3+CD4-CD8-CD69+HLADR+ and are cytotoxic to
      K562 cells. METHODS: In order to determine whether the anti-alphabeta TCD regimen
      was associated with these findings, we compared the reconstitution of gammadelta+
      T cells from patients who received TCD PMRD grafts using the anti-TCRc4 MAb TIOB9
      1A31 (previously reported) with similar patients who received grafts using the
      anti-CD3 MAb OKT3. RESULTS: Increased cytotoxic Vdelta1+ T cells were seen in 10
      of 43 T10B9 TCD patients compared to 7 of 100 in the OKT3 TCD group (23% versus
      7%, p = 0.010). T10B9 patients with increased gammadelta+ T cells also exhibited
      a higher range of increased gammadelta+ T cells and the length of time the
      gammadelta+ T cells remained high was longer when compared to OKT3 patients.
      Patients with increased gammadelta+ T cells whose grafts were T-cell depleted
      with T10B9 showed a significant decrease in relapse (p = 0.038). Similar rates
      and reduction in relapse were seen in OKT3 TCD patients, although significance
      was not reached due to the small number of patients with increased gammadelta+ T
      cells. Estimated 3 year disease-free survival was significantly improved in T10B9
      patients with increased gammadelta+ T cells (0.79 versus 0.31, p = 0.009), a
      trend also seen in OKT3 patients (p = 0.091). DISCUSSION: These observations
      indicate that Vdelta1+CD4-CD8-cytotoxic T cells are associated with lower relapse
      rates and improved survival, and thus may have a role in a graft-versus-leukemia
      effect.

PMID- 19746646
TI  - Variations in the content of CD34+ cells in the peripheral blood of cancer
      patients receiving out-patient chemotherapy.
AB  - BACKGROUND: The routine measurement of CD34+ cells in non-mobilized peripheral
      blood, using flow cytometry, has been limited by the technical difficulty of
      measuring the absolute numbers of rare populations of cells. METHODS: We studied
      the numbers of CD34+ cells in the peripheral blood of 55 normal volunteers and
      476 cancer patients receiving chemotherapy, in a university out-patient
      hematology/oncology clinic. Blood samples were stained with MAbs to CD34, CD45
      and a DNA-specific dye, mixed with a defined number of fluorescent True-Count
      beads and analyzed by flow cytometry, using an automated acquisition and analysis
      program. RESULTS: The mean (+/- SD) CD34+ cell count among normal volunteers and
      previously untreated cancer patients were 1.4 +/- 1.4 and 1.8 +/- 2.8 CD34+
      cells/microL, was stable among normal volunteers and patients receiving
      chemotherapy for prostate or breast cancer. In contrast, the CD34+ cell count
      among patients receiving dose-intensive weekly chemotherapy for the treatment of
      Hodgkin's disease or non-Hodgkin's lymphoma varied between 1 cell/microL to > 300
      CD34+ cells/microL in a predictable and cyclic fashion. DISCUSSION: The study
      demonstrates that the routine measurement of the number of CD34+ cells in
      peripheral blood samples can be performed using an automated single platform
      program in an out-patient setting. The availability of an automated data
      acquisition and analysis program could facilitate standardization of counting
      CD34+ cells in clinical samples analyzed at different laboratory sites.

PMID- 19746647
TI  - Selection of CD34+ cells from cryopreserved PBPC can be significantly improved by
      the addition of recombinant human DNase (Pulmozyme).
AB  - BACKGROUND: It has been reported previously that PBPC can be recovered from
      cryopreservation and can be efficiently CD34-selected, to provide a product of
      high purity (> 80% CD34) with good yield (> 50% recovery). METHODS: In this
      study, we have investigated the effects of thawing and CD34-selecting
      cryopreserved PBPC in the presence of recombinant human deoxyribonuclease
      (rhDNase; Pulmozyme) and magnesium chloride (MgCl2 injection). RESULTS: The
      addition of Pulmozyme and MgCl2 significantly improves the yield of CD34+ cells,
      compared with the standard procedure (65.2% and 39.7%, respectively). Following
      CD34 selection, significantly greater recovery of CFC in the selected fraction
      can be obtained from Pulmozyme-treated cells, compared with standard cells. The
      use of recombinant human Pulmozyme and i.v. grade MgCl2 should facilitate the
      application of this procedure to the clinical setting. CD34+ cells selected from
      cryopreserved PBPC, can in turn be cryopreserved for a second time. When thawed,
      these cells still retained good viability (> 80%). DISCUSSION: Cells originally
      processed in the presence of Pulmozyme gave significantly superior yields of
      CD34+ cells and CFC compared with standard cells. The functional ability of these
      CD34+ cells was demonstrated further in an ex vivo expansion culture system with
      extensive proliferation of cells and CFC. In addition, the presence of
      significant numbers of primitive hemopoietic cells could be readily demonstrated
      in a cobblestone-area forming assay.

PMID- 19746648
TI  - Assays to determine hematopoietic stem cell content in blood or marrow grafts.

PMID- 19746649
TI  - Minimal residual cancer.

PMID- 19746650
TI  - Comparison of lufenuron and nitenpyram versus imidacloprid for integrated flea
      control.
AB  - A one-year field study was carried out in 45 households in Cairns, North
      Queensland to evaluate the efficacy of three topical or systemic treatment
      programs in controlling cat flea (Ctenocephalidesfelis) infestations within the
      residence and on dogs and cats. Homes were randomly assigned to one of three
      treatments. In the first group of homes, lufenuron was administered orally to all
      household pets according to label recommendations for the study duration, and
      nitenpyram was administered orally once per week for the first 6 weeks. After 6
      weeks, all pets in the household received a single dose of nitenpyram if fleas
      were observed on any animal. Treatments in the second group of homes were
      identical to those for the first group except that all pets in the household
      received two doses of nitenpyram per week. In the final group, imidacloprid was
      applied topically to all household pets once every 4 weeks for the duration of
      the study, and no other flea-control measures were applied. Flea populations on
      the pets of all treatment groups were assessed; environmental flea numbers were
      assessed only for Groups 1 and 3. The combination of lufenuron and nitenpyram
      provided superior control of flea populations on the animals and in the
      environment compared with using imidacloprid alone.

PMID- 19746651
TI  - Evaluation of the ability of tilmicosin to prevent adherence of Mycoplasma
      hyopneumoniae to cilia using a differentiated swine respiratory epithelial
      culture system.
AB  - Mycoplasmal pneumonia caused by Mycoplasma hyopneumoniae is a serious economic
      problem for swine producers in the United States. Mycoplasma hyopneumoniae
      colonizes ciliated respiratory epithelial cells. The organism has been shown to
      be sensitive to tilmicosin, a synthetic macrolide, in antibiotic sensitivity
      assays. The efficacy of tilmicosin to inhibit adherence of M. hyopneumoniae to
      ciliated epithelial cells without direct contact between the antibiotic and the
      organism was evaluated using in vitro methods. The study demonstrated that
      tilmicosin inhibited the adherence of M. hyopneumoniae at the highest level
      tested in the system (2 microg/ml) suggesting that tilmicosin may be efficacious
      against mycoplasmal pneumonia.

PMID- 19746652
TI  - An investigation of the relationship between caloric intake and outcome in
      hospitalized dogs.
AB  - Malnutrition in veterinary patients is thought to increase morbidity and
      mortality, but this has not been statistically quantified. A study was designed
      to estimate the proportion of hospitalized canine patients in negative-energy
      balance; relate calories consumed in-hospital to appetite at home shortly after
      discharge; determine why these dogs were in a negative-energy balance; and assess
      the relationship between body condition score, physical status score (PSS),
      diagnosis, and caloric intake with patient outcome. Data were collected from 276
      dogs over several days in one of the various referral hospitals. After
      eliminating partial hospital days, there were 821 dog-days for evaluation. A
      daily positive-energy balance (> 95% resting energy requirement) was achieved for
      only 27% of the 821 full dog-days. Of 226 dogs successfully followed after
      discharge, 83% were considered by their owners to have a normal appetite and/or
      food intake by the second day home. Of the 601 negative-energy-balance dog-days,
      22% were due to poorly written feeding orders and 34% had orders to have feed
      withheld; most cases (44%) resulted from the dog refusing to eat any or all of
      the food offered. There were significant relationships between caloric intake and
      PSS, outcome and PSS, and outcome and caloric intake. In general, canine patients
      with lower PSSs (i.e., no or mild systemic diseases) consumed more daily calories
      and were more likely to be discharged whereas patients with higher PSSs (i.e.,
      incapacitating, life-threatening systemic diseases) were less likely to meet the
      resting energy requirement and be discharged from the hospital.

PMID- 19746653
TI  - Effects of an ivermectin otic suspension on egg hatching of the cat ear mite,
      Otodectes cynotis, in vitro.
AB  - An otic suspension containing 0.01% ivermectin (Acarexx; Blue Ridge
      Pharmaceuticals, Greensboro, NC) controls adult ear mites (Otodectes cynotis),
      but there are no data published on its efficacy against the eggs of this
      parasite. Three in vitro trials were conducted to examine the efficacy of this
      product for prevention of hatching of O. cynotis eggs. Eggs were placed in Petri
      dishes on 1 ml agarose only, agarose with 50 microl of the ivermectin otic
      suspension (low dose), or agarose with 0.5 ml of the otic suspension (full dose).
      In Trials 1 and 2, eggs were held at 28 degrees C; in Trial 3, eggs were kept at
      37 degrees C. After 6 days, 22% to 38% of the eggs hatched in the control
      cultures, compared with 0% to 14% in the low-dose medium, and 0% to 8% of the
      eggs exposed to the full-dose medium. In the controls, larvae hatched throughout
      the 6 days and crawled away from the empty eggshells. Only one other larva (from
      a low-dose plate in Trial 2) crawled away from its eggshell. At the full dose of
      ivermectin, larvae hatched only within the first day of culture, and those few
      that did hatch died immediately. The 0.01% ivermectin otic suspension prevented
      the hatching of larvae from eggs or immediately killed the small number of mites
      that hatched.

PMID- 19746654
TI  - Lymphocyte phenotype subsets in the cerebrospinal fluid of normal horses and
      horses with equine protozoal myeloencephalitis.
AB  - The percentages of T-lymphocytes, lymphocyte subsets CD4+ and CD8+ T-cells, and
      lymphocyte adhesion molecule CD11a/CD18 were determined in the peripheral blood
      and cerebrospinal fluid (CSF) of seven normal horses and four horses with equine
      protozoal myeloencephalitis (EPM) using flow cytometry. There was a greater
      percentage of CD5+ cells in the CSF (79.0%) than in peripheral blood (67.0%),
      although this did not achieve statistical significance. Furthermore, the
      lymphocyte population in CSF comprises a significantly greater (P = .01)
      percentage of CD8+ T-cells, resulting in a decrease of the CD4/CD8 ratio.
      Lymphocyte phenotype subsets in peripheral blood or CSF from horses affected with
      EPM did not differ from normal horses, although CD5+ T-lymphocytes were seen in
      significantly greater numbers in the CSF of EPM-affected horses (93.2%) than in
      normal horses (79.0%).

PMID- 19746655
TI  - Effects of chronic, oral amiodarone on left ventricular pressure,
      electrocardiograms, and action potentials from myocardium in vivo and from
      Purkinje fibers in vitro.
AB  - Left ventricular pressure, electrocardiograms, and action potentials from
      myocardium and Purkinje fibers were recorded from five untreated controls and
      five dogs given amiodarone at 25 mg/kg every 12 hours for 4 weeks, followed by 25
      mg/kg once daily for an additional 6 weeks. QT interval and action potential
      duration were more prolonged following treatment with amiodarone, but there were
      no significant changes in Purkinje fibers except that automaticity was
      suppressed. This study demonstrated that amiodarone given orally for 10 weeks to
      healthy dogs lengthens action potential duration of myocardium but has no effect
      on Purkinje fibers or heart rate variability. This is contrary to previous
      reports of dogs given amiodarone at a lower dose and for shorter times.

PMID- 19746656
TI  - Time course of enrofloxacin and its active metabolite in peripheral leukocytes of
      dogs.
AB  - The accumulation of fluoroquinolones in peripheral leukocytes is well established
      for several members of this family of drugs. This study documented accumulation
      of enrofloxacin and its active metabolite, ciprofloxacin, in canine peripheral
      leukocytes after oral administration at 7.5, 10, or 20 mg/kg, doses that are
      within the currently approved label of Baytril (Bayer Corporation Animal Health,
      Shawnee Mission, KS) in the United States. Accumulation index, as defined by
      C(max) in white blood cells (WBCs) divided by C(max) in plasma at the same time
      points, ranged from 47-fold to 63-fold for enrofloxacin and 28- to 35-fold for
      ciprofloxacin. Time course of both enrofloxacin and ciprofloxacin in WBCs
      paralleled the time course in plasma. Disappearance half-life of ciprofloxacin
      from WBCs was significantly (P = .001) longer than was enrofloxacin (P= .015) for
      all doses studied. The accumulation of enrofloxacin in peripheral leukocytes may
      contribute to the antimicrobial efficacy of this compound.

PMID- 19746657
TI  - Safety of an oral chondroprotective agent in horses.
AB  - Six healthy, adult female horses were administered five times the minimum
      maintenance dose of an oral low-molecular-weight chondroitin sulfate, glucosamine
      HCl, and manganese ascorbate chondroprotective agent (Cosequin; Nutramax
      Laboratories, Inc., Edgewood, MD) daily for 35 days. Hematology, serum
      biochemistry, and synovial fluid parameters were assessed twice prior to
      administering the product and again at the end of the treatment period. Physical
      examinations performed daily throughout the study showed no abnormal clinical
      changes attributable to the product. All hematologic parameters measured were
      within normal reference ranges; however, hematocrit, hemoglobin, and white blood
      cell counts were significantly (P < .05) increased after treatment, as compared
      with values on Day 0. Mean serum urea nitrogen was mildly elevated above the
      reference range before and after treatments, and mean serum creatinine was
      significantly (P < .05) decreased after treatment. Several other biochemical
      parameters (calcium, phosphorus, potassium, total and indirect bilirubin,
      alkaline phosphatase, gamma-glutamyltransferase, lactic dehydrogenase, and
      sodium:potassium ratio) were significantly (P < .05) altered following
      administration of the chondroprotectant, but all remained within normal reference
      ranges. Mean creatine kinase levels were significantly higher after treatment
      than on Day 0 (429 U/L versus 310 U/L), but this represented only a mild
      elevation relative to the reference range (10 to 350 U/L). Synovial fluid total
      protein and specific gravity were unaffected. The minor shifts encountered in
      hematology and serum biochemistry parameters are not considered to have clinical
      significance. The results of this study suggest that the oral chondroprotective
      agent tested is safe for administration to horses at recommended dose rates.

PMID- 19746658
TI  - Experimental fetal challenge using type II bovine viral diarrhea virus in cattle
      vaccinated with modified-live virus vaccine.
AB  - Nineteen open heifers or cows were vaccinated 45 days prior to breeding with a
      modified-live bovine viral diarrhea virus (BVDV) vaccine. An additional six
      animals were not vaccinated and served as controls. All 25 animals were estrus
      synchronized and bred. At 75 days of gestation, the 25 pregnant animals were
      experimentally infected with a type II isolate of BVDV by intranasal inoculation.
      At 75 days after inoculation, the animals were euthanized and each fetus was
      removed and retained for sampling. Virus isolation was accomplished from fetal
      tissues (spleen, thymus, and small intestine). Type II BVDV was isolated from the
      fetuses collected from all six unvaccinated control animals and from eight of 19
      fetuses from vaccinated animals, which were determined to be persistently
      infected following experimental challenge.

PMID- 19746659
TI  - Evaluation of the effects of omeprazole on physiological indices of performance
      of horses during incremental treadmill exercise.
AB  - Omeprazole is a proton-pump inhibitor recently approved in the United States for
      the treatment of gastric ulcer disease in horses. A study was designed to
      determine the effects of omeprazole treatment on the physiological indices of
      performance of horses during incremental treadmill exercise. In a crossover
      design study carried out over 2 weeks, five horses completed standardized
      incremental exercise tests on a high-speed treadmill either with no treatment or
      treatment with omeprazole. No statistically significant effects of omeprazole
      were found on the mean maximum responses for specific oxygen consumption,
      specific carbon dioxide production, number of steps completed, concentration of
      plasma lactate, heart rate achieved, or total run time during the standardized
      incremental exercise protocol. The results indicate omeprazole treatment is
      unlikely to be associated with marked enhancement of athletic performance.

PMID- 19746660
TI  - Relationship between circulating and dietary taurine concentrations in dogs with
      dilated cardiomyopathy.
AB  - A retrospective study was conducted to determine dietary taurine concentrations
      in dogs with dilated cardiomyopathy (DCM) and to compare the clinical outcome of
      taurine-deficient and non-taurine-deficient dogs. Taurine concentrations were low
      in blood samples from 20 of 37 dogs with DCM. Median dietary taurine
      concentration was not significantly different between taurine-deficient and
      nondeficient dogs. There was no correlation between dietary and circulating
      taurine concentrations. The outcome of taurine-deficient dogs supplemented with
      taurine was not different from the outcome of nondeficient dogs. The role
      oftaurine and its relationship to dietary intake in canine DCM remain unclear.

PMID- 19746661
TI  - Effects of dietary fat and carnitine on urine carnitine excretion in healthy
      dogs.
AB  - Turnover of carnitine in the body is primarily the result of renal excretion, and
      high-fat (HF) diets have been shown to increase urine carnitine excretion in
      healthy people. Recently, increased renal excretion of carnitine was observed in
      dogs diagnosed with cystinuria and carnitine deficiency. Carnitine deficiency has
      been linked to dilated cardiomyopathy and lipid storage myopathies in dogs and
      humans, and low-fat (LF) diets have been beneficial in some human patients with
      carnitine deficiency. In addition, HF, protein-restricted diets are often
      recommended for management of cystinuria in dogs. However, whether HF diets
      increase renal carnitine excretion in dogs or whether dogs with carnitine
      deficiency would benefit from LF diets remains unknown. Therefore, the purpose of
      this study was to determine the influence of dietary fat and carnitine on renal
      carnitine excretion in healthy dogs. Results from this study revealed that an HF
      diet increased urine carnitine excretion in dogs; however, carnitine excretion
      with the HF diet was not significantly different from that in dogs consuming an
      LF diet. Nonetheless, these results raise the possibility that increased renal
      carnitine excretion associated with HF diets could be one risk factor for
      development of carnitine deficiency in dogs with an underlying disorder in
      carnitine metabolism, and some dogs with carnitine deficiency may benefit from an
      LF diet. Another important observation in this study was that renal excretion of
      carnitine exceeded dietary intake in all diet groups, confirming previous reports
      that concluded that canine renal tubular cells reabsorb carnitine poorly when
      compared with those of humans.

PMID- 19746662
TI  - Response of dogs treated with ivermectin or milbemycin starting at various
      intervals after Dirofilaria immitis infection.
AB  - The response to heartworm infection before preventative programs were started was
      investigated in 56 dogs. Dogs were infected with third-stage larvae of
      Dirofilaria immitis and started on preventative programs (monthly treatment) with
      ivermectin/pyrantel pamoate (IVM/PP) or milbemycin oxime (MO) 3.5, 4.5, 5.5, or
      6.5 months after infection. Each time period comprised a group of six dogs
      treated with IVM/PP and six treated with MO. Thoracic radiographs were obtained
      prior to infection, at the start of preventative treatment, and at regular
      intervals until dogs were necropsied 1 year after the preventative was started.
      All dogs developed radiographic signs of heartworm disease, and all had heartworm
      related arterial changes at necropsy. From Day 210 to 330, interstitial lung
      disease was less severe in dogs started on MO 3.5 months after infection than in
      dogs given IVM/PP at the same time. Arterial surfaces were more severe at
      necropsy in the dogs started on MO at 4.5 months than in the dogs started on
      IVM/PP at the same time. There was increased caudal lobar arterial and
      interstitial disease in the dogs treated with IVM/PP compared with dogs treated
      with MO; this was attributed to the death of young worms within the caudal
      pulmonary arteries. Dogs started on either preventative at 5.5 and 6.5 months
      after infection had radiographic changes and necropsy evaluations that were
      similar to those of untreated controls. This study reinforces the recommendation
      of the American Heartworm Society that mature dogs be evaluated for infection
      prior to starting a monthly preventative and that any dog that tests positive by
      a heartworm antigen test receive treatment with an adulticide prior to starting a
      heartworm preventative program.

PMID- 19746663
TI  - Control of fleas on dogs and cats and in homes with the combination of oral
      lufenuron and nitenpyram.
AB  - Efficacy of lufenuron (Program, Novartis Animal Health, Greensboro, NC), an
      insect growth regulator, and nitenpyram (Capstar, Novartis Animal Health), an
      insecticide for reducing flea populations, was evaluated in 35 flea-infested dogs
      and cats residing in 18 households in Tampa, Florida. Pets were randomly
      allocated by household to two treatment groups. Pets in both treatment groups
      were given lufenuron orally according to label directions on Day 0, then once a
      month for 3 months. Pets in one group were also given nitenpyram tablets by the
      owner orally once a day every other day. Pets in the second group were given
      nitenpyram by their owners as needed but no more frequently than once daily. Flea
      numbers on pets and in homes were assessed throughout the study by the use of
      visual body area counts and intermittent-light traps, respectively. The
      combination of lufenuron and nitenpyram reduced flea populations on pets by at
      least 97.3% within 7 days and maintained this rate of reduction in flea numbers
      for the duration of the study, regardless of which regimen was used for
      administering nitenpyram. For either group, premise flea counts were reduced by
      up to 89.5% by Day 28 and by as much as 100% by Days 84 to 90.

PMID- 19746664
TI  - Efficacy of ponazuril 15% oral paste as a treatment for equine protozoal
      myeloencephalitis.
AB  - Equine protozoal myeloencephalitis (EPM) is a neurologic disease of horses most
      commonly caused by the protozoan parasite Sarcocystis neurona. Until recently the
      only treatment option was the combination of a sulfonamide with pyrimethamine.
      The present study was performed to assess the efficacy of ponazuril, an
      anticoccidial triazine-based compound, as a treatment for naturally occurring
      EPM. One hundred one horses with EPM were randomly allocated to treatment with
      ponazuril 15% oral paste at either 5 or 10 mg/kg body weight for 28 consecutive
      days. Horses were evaluated clinically and by analysis of blood and cerebrospinal
      fluid (CSF) before and 28 and 118 days after the start of treatment. Clinical
      success was defined as either an improvement in neurologic score by at least one
      grade (on a 0 to 5 scale) or conversion to negative status on Western blot for S.
      neurona antibodies by 90 days following cessation of treatment. Overall, 62% of
      the horses, including 28 of 47 treated with ponazuril at 5 mg/kg and 35 of 54
      treated with 10 mg/kg, met the criteria for successful treatment. The Western
      blot for CSF became negative in 10% (10/101) of the horses. Quantification of the
      anti-17kDa antibody response in Western blot (relative quantity CSF) did not
      reveal a significant change in response to treatment. However, immunoglobulin
      index did decrease significantly during treatment (P = .01). The findings of this
      study support the efficacy of ponazuril for the treatment of EPM.

PMID- 19746665
TI  - Safety of ponazuril 15% oral paste in horses.
AB  - Ponazuril, a triazine-derivative compound, is proposed as a treatment for equine
      protozoal myeloencephalitis caused by Sarcocystis neurona. Ponazuril 15% oral
      paste was administered to 24 horses at 0, 10, or 30 mg/kg body weight for either
      28 or 56 days, representing zero, two, and six times the proposed dosage rate and
      one and two times the recommended duration of treatment, respectively. Serum
      chemistry analysis, coagulation profile, and hematology measurements were
      performed weekly and necropsy evaluations, including histopathology, were
      conducted for all animals at the end of the study. Minimal reactions were noted
      during the treatment period. Soft stools were observed in four of 16 treated
      horses and three of eight control animals. Serum blood urea nitrogen levels
      increased and serum sodium levels decreased in horses receiving 10 mg/kg;
      however, these changes were not associated with number of days on treatment and
      no value for either variable was outside the normal reference range. No signs of
      colic were observed in any treated animal during the study. At necropsy, uterine
      edema was noted in three of the four mares treated with ponazuril at 30 mg/kg. No
      other treatment-related postmortem or histologic abnormalities were identified in
      any of the horses. These findings suggest that ponazuril has minimal toxic
      potential when dosed at levels up to six times the recommended clinical dosage
      and for one or two times longer than the recommended duration.

PMID- 19746666
TI  - Cerebrospinal fluid and serum concentrations of ponazuril in horses.
AB  - Ponazuril was administered orally to 10 adult horses at 5 mg/kg body weight, once
      a day for 28 days. Blood was collected once a week from each horse from Days 0
      through 35, daily from Days 35 through 42, and on Day 49. Cerebrospinal fluid
      (CSF) was also collected once a week from Day 0 through Day 49. Concentrations of
      ponazuril in the serum and CSF were determined, and pharmacokinetic calculations
      were performed. Ponazuril was readily absorbed following oral administration; and
      after 7 days of dosing, the serum concentration was 4.33 +/- 1.10 mg/L, and the
      mean CSF concentration was 0.162 +/- 0.05 mg/L. Cerebrospinal fluid concentration
      did not vary during the 28 days of dosing and concentrations declined rapidly
      after cessation of administration on Day 28. The terminal elimination half-life
      ofponazuril in serum (using Day 28 to 42 results) was 4.3 +/- 0.6 days. Repeated
      CSF collections from the atlanto-occipital space did not induce changes in the
      immunoglobulin G index or albumin quotient. It was concluded that oral
      administration of ponazuril to healthy horses at 5 mg/kg provided concentrations
      of ponazuril in the CSF that are presumed to be adequate for the treatment of
      equine protozoal myeloencephalitis (EPM). These results indicate that this dosage
      rate should be investigated for efficacy against EPM.

PMID- 19746667
TI  - Use of a high-protein diet in the management of feline diabetes mellitus.
AB  - A study was conducted to evaluate the clinical response of diabetic cats to a
      high-protein, low-carbohydrate diet. Adult cats with diabetes mellitus of at
      least 4 months' duration were recruited and fed a high-fiber, moderate-fat canned
      diet for 1 to 2 months during the standardization period. All cats were then
      transitioned to a high-protein, low-carbohydrate canned diet for a 3-month
      treatment period. Analyses of treatment effect included hematology, serum
      biochemistry, fructosamine, lipid profile, and postprandial glucose curves. Cats
      were also monitored for changes in body weight, appetite, activity level, urinary
      habits, and insulin requirements. Nine cats completed the study protocol. All
      cats remained generally stable throughout the treatment period, although there
      was a slight overall improvement in activity. Insulin levels were decreased in
      eight of the nine cats when transitioned from the high-fiber diet to the high
      protein diet, and insulin injections were completely stopped in three of the
      cats. Results of regression analysis indicated that exogenous insulin could be
      reduced by over 50% with no loss in glucose control, as measured by serum
      fructosamine. Results of this study support the use of a high-protein, low
      carbohydrate diet in the management of cats with diabetes mellitus.

PMID- 19746668
TI  - Brain aging in dogs: parallels with human brain aging and Alzheimer's disease.
AB  - Differentiating normal from pathologic aging is a challenge to veterinarians
      treating geriatric patients and to clinicians diagnosing Alzheimer's disease.
      Part of the difficulty stems from the lack of a biological marker. Dogs and
      humans develop similar cognitive dysfunction with age, and a subset of
      individuals develop severe impairments. Similar neuropathology also develops in
      the brains of elderly humans, individuals with Alzheimer's disease, and dogs.
      Both species develop senile plaque neuropathology, with more extensive plaque
      accumulation associated with severe cognitive impairments. This article discusses
      similarities in the clinical features and development of neuropathology with age
      in both dogs and humans and provides a discussion of treatment options.

PMID- 19746669
TI  - Evaluation of a topical solution containing 65% permethrin against the sandfly
      (Phlebotomus perniciosus) in dogs.
AB  - A topical solution containing 65% permethrin (EXspot, Schering-Plough Animal
      Health Corp., Union, NJ) was evaluated for repellency and insecticidal activity
      against the phlebotomine sandfly, Phlebotomus perniciosus (Diptera: Psychodidae).
      Four dogs were sedated and individually exposed to 100 female P. perniciosus
      inside a cage. Two of the dogs were treated on Day 0 with the permethrin solution
      by application of a 2-ml dose directly on the skin along the dorsal midline from
      the dorsal scapular area to the base of the tail. Two dogs remained untreated as
      controls. On Days -8, 0, 7, 14, 21, 28, 35, 49, 70, and 91, sandfly landings were
      recorded during the first 5 minutes of an insect exposure period and insect
      feeding and mortality rates were recorded after 1 hour of exposure. The number of
      sandfly landings was moderately decreased, and insect feeding rates decreased to
      zero by Day 7. From Day 14 through Day 28, the number of insect feedings was
      reduced from control values by greater than 90%. These findings indicate the
      permethrin spot-on provided a considerable repellent effect. Insect mortality
      rates remained very high (about 61%) during the 5 weeks after application,
      although insecticidal effects persisted for more than 7 weeks in total. These
      data suggest that monthly application of this topical solution of permethrin from
      the end of spring until the beginning of fall may protect dogs from the majority
      of sandfly bites. Further investigation with greater numbers of animals is
      warranted; however, results of this preliminary investigation indicate that a
      leishmaniasis control program that incorporates the strategic use of this product
      on dogs can be expected to decrease the number of infected animals and the
      incidence of the disease among the canine population.

PMID- 19746670
TI  - The effects of pyrantel tartrate on Sarcocystis neurona merozoite viability.
AB  - Sarcocystis neurona is the etiologic agent of equine protozoal myeloencephalitis,
      a neurologic disease of horses. The present study was designed to test the
      hypothesis that pyrantel tartrate can kill S. neurona merozoites growing in
      equine dermal cell culture. Sarcocystis neurona merozoites were exposed to a
      range of concentrations of pyrantel tartrate or sodium tartrate ranging from
      0.001 to 0.01 M. Merozoites were then placed onto equine dermal cell cultures and
      incubated for 2 weeks to check for viability. At 1 and 2 weeks after inoculation,
      plaque counts were compared between treatments and, between treatments and
      controls. Merozoites exposed to concentrations of pyrantel tartrate higher than
      0.0025 M (8.91 x 10(-4) g/ml) did not produce plaques in equine dermal cells,
      whereas those exposed to similar concentrations of the tartrate salt or medium
      alone produced significant numbers of plaques. These results demonstrate that
      pyrantel tartrate has activity against S. neurona merozoites in vitro and suggest
      that it may have activity against the sporozoite stage of the parasite found in
      the equine gut.

PMID- 19746671
TI  - Do topical retinoids cause acne to "flare"?
AB  - BACKGROUND: Guidelines support this use of topical retinoids as a fundamental
      part of acne treatment regimens. However, existing dogma holds that topical
      retinoids may initially worsen acne. PURPOSE: To review the available data from
      clinical trials for evidence of initial worsening of acne with topical retinoids.
      METHODS: A PubMed and Google Internet search was performed for sources indicating
      or refuting worsening of acne with topical retinoids. RESULTS: No primary data
      from clinical trials were identified to support the dogma of acne worsening
      secondary to topical retinoids. Available data point to topical retinoids
      improving acne, even during the first couple weeks of treatment. CONCLUSION: It
      is unlikely that acne worsens or "flares" due to the initiation of topical
      retinoids. Some acne patients may have worsening of acne during the first week or
      two as part of the natural disease process.

PMID- 19746672
TI  - Clinical role and application of superficial chemical peels in today's practice.
AB  - Chemical peeling is a popular, relatively inexpensive, and generally safe method
      to refresh and rejuvenate skin. This review focuses on superficial chemical peels
      and their use in routine clinical practice. A wide variety of peels are
      available, utilizing various actives and concentrations, including a recently
      introduced salicylic acid derivative, beta-lipohydroxy acid, which has properties
      that may expand the clinical use of peels. Superficial peels can be used to
      enhance treatment within a variety of conditions, including acne, melasma,
      dyschromias, photodamage and actinic keratoses. In addition, peels can be
      combined with other in-office procedures to optimize outcomes and enhance patient
      satisfaction, and allow clinicians to tailor the treatment to individual
      patient's needs. Successful outcomes are based on a thorough understanding and
      application of correct chemical peel procedures, including history-taking,
      pretreatment, preparation, peel selection, patient communication and maintenance
      regimens.Used properly, the superficial chemical peel has the potential to fill
      an important therapeutic need in the treatment armamentarium of dermatologists
      and plastic surgeons.

PMID- 19746673
TI  - Comparing a novel solubilized benzoyl peroxide gel with benzoyl
      peroxide/clindamycin: final data from a multicenter, investigator-blind,
      randomized study.
AB  - INTRODUCTION: A solubilized 5% BPO gel has been developed to enhance the
      bioavailability, follicular penetration, and efficacy of BPO. METHODS: Sixty-five
      patients with moderate facial acne vulgaris were randomly assigned to apply
      solubilized 5% BPO gel to one facial side and 5% BPO/1% clindamycin to the
      contralateral side, twice daily for four or 12 weeks. RESULTS: The solubilized
      BPO gel resulted in significantly greater reductions in non-inflammatory lesion
      count than BPO/clindamycin at weeks 1, 2, 3, 4 and 12 and comparable reductions
      in inflammatory lesion count at all time points. Mean values for patient
      satisfaction with acne improvement were comparable and mean levels of erythema,
      dryness, peeling, stinging/burning and itching were consistently less than mild.
      CONCLUSION: Compared with BPO/clindamycin, the solubilized BPO gel offers
      significantly greater reductions in non-inflammatory lesion count and comparable
      reductions in inflammatory lesion count in the absence of an antibiotic.

PMID- 19746674
TI  - Laser treatment of dark skin: a review and update.
AB  - Of the estimated 11.7 million cosmetic surgical and nonsurgical procedures
      performed in the United States (U.S.) in 2007, 22% were performed on racial and
      ethnic minorities. Laser and light treatments rank in the top five most requested
      procedures in annual surveys of cosmetic and dermatologic surgeons. Recent U.S.
      population statistics reveal dramatically shifting demographics that would
      anticipate a likely increase in this percentage. U.S. Census Bureau data projects
      that by 2050, people of color are expected to become the majority, comprising 54%
      of the U.S. population, with Latinos accounting for 30%, African Americans 15%,
      and Asians 9.2%. The rising popularity of cutaneous laser surgery as an accepted
      therapy for various skin pathologies, coupled with the diverse face of the
      patient population, has led to increased demand for laser treatment of darker
      skin tones. Although difficult, effective laser therapy in patients with darker
      skin phototypes can be achieved. When determining a treatment protocol for an
      individual patient, the proper laser energy and wavelength are important in
      ensuring a substantial margin of safety while still achieving satisfactory
      results.

PMID- 19746675
TI  - Two-center Canadian report on the safety and effectiveness of Evolence Breeze.
AB  - Evolence Breeze, a new less viscous form of the ribose crosslinked Israeli
      porcine collagen Evolence, was approved for use in Canada as a cosmetic soft
      tissue augmenting agent on July 14, 2006. The purpose of this report is to review
      a one-year, 312 subject, pan facial injection site experience. This represents
      our initial experience with both subject satisfaction and product safety during
      this one year period approximately 1.5 years after Health Canada product
      approval.

PMID- 19746676
TI  - A randomized controlled trial of a low-dose combined oral contraceptive
      containing 3 mg drospirenone plus 20 microg ethinylestradiol in the treatment of
      acne vulgaris: lesion counts, investigator ratings and subject self-assessment.
AB  - OBJECTIVE: To assess the efficacy of a combined oral contraceptive (COC)
      containing 3 mg drospirenone (drsp) plus 20 microg ethinylestradiol (EE)
      administered in 24 days of active treatment followed by a four-day hormone-free
      interval (24/4 regimen) compared with placebo for the treatment of moderate acne
      vulgaris. METHODS: Healthy females (14-45 years old) with moderate facial acne
      were randomized to 3 mg drsp/20 microg EE 24/4 (n = 270) or placebo (n = 268) for
      six cycles. The secondary efficacy variables measured included change from
      baseline to endpoint (cycle 6) in individual lesion count for nodules, papules,
      pustules, open and closed comedones. RESULTS: There were significantly greater
      reductions in individual lesion counts from baseline to endpoint in the 3 mg
      drsp/20 microg EE group than in the placebo group (P < 0.05 from parametric
      model). CONCLUSION: The 3 mg drsp/20 microg EE COC administered in a 24/4 regimen
      significantly reduced acne lesions.

PMID- 19746677
TI  - Use of clofazimine in dermatology.
AB  - Clofazimine is the riminophenazine dye that, due to its antibacterial and anti
      inflammatory properties, has been used for several diseases. This article reviews
      all major characteristics and uses relating to clofazimine, from its pharmacology
      to its indications in several skin diseases, over and above its classical and
      well established use in the treatment of leprosy. Due to its anti-inflammatory
      and antimicrobial properties, clofazimine has a wide spectrum for application in
      dermatology. The indications include neutrophilic, granulomatous and infectious
      diseases. Although it is not the first-choice medication in most of the cases,
      clofazimine should always be considered among the therapeutic options in
      refractory cases.

PMID- 19746678
TI  - Use of eye shields and eye lubricants among oculoplastic and Mohs surgeons: a
      survey.
AB  - BACKGROUND: Eye shields and lubricants are recommended for use in the eye during
      periorbital surgery to prevent injury to the globe. Nonetheless, data regarding
      their use is sparse, and no study to date has examined the prevalence of their
      usage and complications. PURPOSE: To investigate how commonly eye shields and
      lubricants are used during periorbital surgery and whether there are
      complications from their use. METHODS: The authors conducted a survey of
      oculoplastic and Mohs surgery fellowship directors. The questionnaire
      investigated the prevalence of use of eye shields and lubricants, complications
      encountered, and whether the standard of care requires or prohibits their use.
      RESULTS: A majority of those surveyed at least sometimes use eye shields in
      periorbital surgery, particularly to prevent patient injury. Most surgeons
      believe there are more pros than cons to their use. However, corneal abrasions
      may be encountered and may be related to the type of lubricant chosen. Surgeons
      using fat-based lubricants tended to encounter more complications with eye shield
      use. CONCLUSION: Eye shield and lubricant use is common among oculoplastic and
      Mohs surgeons. However, most disagree as to whether the standard of care requires
      or forbids their use.

PMID- 19746679
TI  - Benefits of using a hydroquinone/tretinoin skin care system in patients
      undergoing intense pulsed light therapy for photorejuvenation: a placebo
      controlled study.
AB  - A hydroquinone/tretinoin (HQ/tret) skin care system designed for use with non
      surgical facial rejuvenation procedures has recently become available. In this
      observer-masked study, 36 patients with moderate-to-severe wrinkling of the skin
      around the eyes and lips were randomly assigned to use either the 4%
      hydroquinone/0.05% tretinoin skin care system or placebo products, each day for
      90 days. In addition, all patients received intense pulsed light (IPL) treatment
      on days 30 and 60. At day 90, > or = 75% overall improvement was reported in 72%
      and 19% of patients in the HQ/tret + IPL group and the placebo + IPL group,
      respectively. HQ/tret + IPL was also associated with significantly lower mean
      hyperpigmentation scores at days 30, 60 and 90 (P < or = 0.05), and significantly
      lower mean laxity scores at day 90 (P< or =0.05) compared with placebo + IPL.
      Adjunctive use of the HQ/tret system enhances the improvements in facial skin
      achieved with IPL treatment.

PMID- 19746680
TI  - Concurrent antiphospholipid syndrome and cutaneous [corrected] sarcoidosis due to
      interferon alfa and ribavirin treatment for hepatitis C.
AB  - Autoimmune phenomena are common in both hepatitis C infection and interferon alfa
      treatment; however, the development of antiphospholipid syndrome is rare. This
      article reports the case of a patient who developed antiphospholipid syndrome in
      addition to cutaneous sarcoidosis in the setting of pegylated interferon alfa and
      ribavirin treatment for hepatitis C.

PMID- 19746681
TI  - Two cases of chronic atopic dermatitis treated with soluble tumor necrosis factor
      receptor therapy.
AB  - Atopic dermatitis (AD) is a chronic inflammatory disease that is mediated by
      cytokines. In patients with AD, the use of tumor necrosis factor (TNF)
      antagonists has had unpredictable results. Clinically significant improvements in
      skin symptoms of AD were observed in two patients with severe, chronic disease
      who were treated with the soluble TNF receptor etanercept. These observations
      suggest that etanercept therapy may be beneficial in patients with AD,
      particularly chronic variants with lichenification. Studies to identify features
      of AD that may predict responsiveness to etanercept therapy in these patients are
      warranted.

PMID- 19746682
TI  - Hyperpigmentation: old problem, new therapies.
AB  - Hyperpigmentation has frustrated men and women as a cosmetic concern and as a
      reminder of past skin injury. While photoprotection is an important part of
      preventing dark marks on skin, therapeutic interventions are important as well.
      The authors review new treatment data for fractional thermolysis,Tri-Luma,
      azelaic acid and chemical peels. Many therapies have been available for years,
      although evidence is not always extensive. The emergence of new treatments and
      long-term safety data offers dermatologists a greater degree of confidence as to
      the treatment approaches they can offer patients with hyperpigmentation.

PMID- 19746683
TI  - Are you ready for some changes?

PMID- 19746684
TI  - Government takes first step in defining 'meaningful use' requirement for EHR
      incentives.

PMID- 19746685
TI  - What to do when employees are accused of drug use?

PMID- 19746686
TI  - When office-based physicians code badly. Overcoding for hospital services.

PMID- 19746687
TI  - A peek over the horizon. Strategies to thrive in a down economy.

PMID- 19746688
TI  - ASCs: it's time to take the gloves off. Tips to fight for market share.

PMID- 19746689
TI  - How you can find--and keep--nonphysician providers.

PMID- 19746690
TI  - Do digital faxing first.

PMID- 19746691
TI  - To hit the bull's-eye, you need a target. Use your mission, vision statements to
      meet challenges, focus staff.

PMID- 19746692
TI  - Fill in the blanks. 8 steps to make your practice competitive in the physician
      hiring game.
AB  - A swelling U.S. population and a shrinking supply of physicians to care for it
      means trouble for medical groups seeking to recruit doctors. But forewarned is
      forearmed: Use these tips to put your practice in the best possible position to
      attract new hires.

PMID- 19746693
TI  - Holy headache. Accommodating employees' religious beliefs and practices.
AB  - How much accommodation does your practice have to make for employees' religious
      beliefs? Recent court decisions offer guidance.

PMID- 19746695
TI  - How her garden does grow. Mona Majors, CMPE, president, Operational Solutions
      Inc., Ocala, Fla.

PMID- 19746694
TI  - Together ... yet separate. How your medical group can achieve integration with a
      hospital--without hospital employment.
AB  - How can you achieve more competitive compensation for your group and avoid the
      downsides of hospital employment? Consider a full-practice professional services
      agreement.

PMID- 19746696
TI  - More feedback on whether atrazine is a potent endocrine disruptor chemical.

PMID- 19746697
TI  - Consumer culture keeps carbon emissions high.

PMID- 19746698
TI  - Isotopes finger fertilizer's perchlorate legacy.

PMID- 19746699
TI  - Is regulation on ocean acidification on the horizon?

PMID- 19746700
TI  - Pennsylvania to regulate salt discharges.

PMID- 19746701
TI  - Source separation: will we see a paradigm shift in wastewater handling?

PMID- 19746702
TI  - A new planning and design paradigm to achieve sustainable resource recovery from
      wastewater.

PMID- 19746703
TI  - Determination of halogenated natural products in passive samplers deployed along
      the Great Barrier Reef, Queensland/Australia.
AB  - Halogenated natural products (HNPs) have been increasingly reported to occur in
      marine wild life from all oceans. Several HNPs, such as 2,3,3',4,4',5,5'
      heptachloro-1'-methyl-1,2'-bipyrrole (1) and 4,6-dibromo-2-(2',4'
      dibromo)phenoxyanisole (2'-MeO-BDE 68 or BC-2), were detected at particularly
      high concentrations in dolphins from Queensland/Australia. About half of the
      coastline of Queensland (approximately 2500 km) is covered by the Great Barrier
      Reef, a rich ecosystem hosting a huge variety of species, many of which are known
      to produce natural compounds. In this study, semipermeable membrane devices
      (SPMDs) were deployed as passive samplers for about 30 days at 12 marine and 2
      nonmarine sites (i.e., rivers) along the Great Barrier Reef as part of a routine
      monitoring program during November 2007 and May 2008. Q1 and 2'-MeO-BDE 68 were
      detected at the marine sites with frequencies of about 65% but not in any sample
      from the two rivers. Further HNPs (2,4,6-tribromophenol, TBP; 2,4,6
      tribromoanisole, TBA; 2,2'-dimethoxy-3,3'5,5'-tetrabromobiphenyl, 2,2'-diMeO-BB
      80 or BC-1; 3,5-dibromo-2-(2',4'-dibromo)phenoxyanisole, 6-MeO-BDE 47 or BC-3;
      and 3,5-dibromo-2-(3',5'-dibromo,2'-methoxy)phenoxyanisole, 2',6-diMeO-BDE 68 or
      BC-11) were detected as well with frequencies of 18-97% in the marine samples,
      but no polybrominated flame retardants were detected. The highest amount of a
      single HNP, 2.3 microg/SPMD, was determined for TBP, which had a frequency of
      detection of only 46%. The maximum (average) amount in the SPMDs from marine
      sites was 44 ng (12 ng) for (1 and 115 ng (20 ng) for 2'-MeO-BDE 68. A first
      order kinetic model was used to estimate concentrations of the HNPs in the water
      phase. Based on the depuration of performance reference compounds obtained at one
      of the sites, we assumed a sampling rate of 16 L/day. We used this sampling rate
      to estimate that the highest and average available concentrations of Q1 in the
      water during the deployment of the SPMD were 97 and 25 pg/L, respectively. The
      estimated maximum water concentrations of 2'-MeO-BDE 68, 2,2'-diMeO-BB 80, 6-MeO
      BDE 47, and 2',6-diMeO-BDE 68 were on average 2-5.5 fold higher than that of Q1.
      The results confirm that the HNPs are produced throughout the Great Barrier Reef,
      which appears to be a significant source of these compounds.

PMID- 19746704
TI  - Population dynamics of iron-oxidizing communities in pilot plants for the
      treatment of acid mine waters.
AB  - The iron-oxidizing microbial community in two pilot plants for the treatment of
      acid mine water was monitored to investigate the influence of different process
      parameters such as pH, iron concentration, and retention time on the stability of
      the system to evaluate the applicability of this treatment technology on an
      industrial scale. The dynamics of the microbial populations were followed using T
      RFLP (terminal restriction fragment length polymorphism) over a period of several
      months. For a more precise quantification, two TaqMan assays specific for the two
      prominent groups were developed and the relative abundance of these taxa in the
      iron-oxidizing community was verified by real-time PCR. The investigations
      revealed that the iron-oxidizing community was clearly dominated by two groups of
      Betaproteobacteria affiliated with the poorly known and not yet recognized
      species "Ferrovum myxofaciens" and with strains related to Gallionella
      ferruginea, respectively. These taxa dominated the microbial community during the
      whole investigation period and accelerated the oxidation of ferrous iron despite
      the changing characteristics of mine waters flowing into the plants. Thus, it is
      assumed that the treatment technology can also be applied to other mine sites and
      that these organisms play a crucial role in such treatment systems.

PMID- 19746705
TI  - Exposure analysis of bisphenol A in surface water systems in North America and
      Europe.
AB  - This study was conducted to develop a statistical understanding of exposures to
      bisphenol A (BPA) in aquatic environments in North America and Europe.
      Concentrations of BPA have been reported by 89 investigations published between
      1997 and 2007. On the basis of an analysis of weighted observations (n = 1068 and
      848 for North America and Europe, respectively), BPA was reported at
      concentrations above the detection limit in 20-51% of freshwater samples. Median
      BPA concentrations for fresh surface waters for North America and Europe were
      0.081 and 0.01 microg/L, respectively, while 95th percentiles were 0.47 and 0.35
      microg/L, respectively. In contrast to fresh surface waters, only limited data
      are available for sediments and less for marine ecosystems. For freshwater
      sediments in North America (n = 71), the median and 90th percentile concentration
      (the 95th percentile was not calculable) were 0.6 and 3.4 ng/ g-dw, respectively,
      while the median and 95th percentile concentration in Europe (n = 249) were 16
      and 256 ng/g-dw, respectively. To assess the potential ecological significance,
      we compared exposure concentrations with available regulatory criteria. The
      results suggest the frequency of locations in which concentrations are likely to
      cause adverse effects on aquatic ecosystems is low, with the exception of
      sediments collected from some highly urbanized and industrial locations.

PMID- 19746706
TI  - Occurrence and origin of estrogenic isoflavones in Swiss river waters.
AB  - We report results from a systematic one-and-a-half year survey of the estrogenic
      isoflavones formononetin (FOR), biochanin A (BIO), daidzein (DAI), genistein
      (GEN), and equol in Swiss midland rivers. FOR was detected in about 90%, the
      other compounds in 13-56% of the weekly and fortnightly integrated flow
      proportional samples. Concentrations were mostly in the lower ng/L-range, with a
      maximum of 524 ng/L and 217 ng/L for equol and FOR, respectively. Due to
      dilution, concentrations were river discharge dependent with higher numbers in
      smaller rivers. Total isoflavone loads were in the order of a few kg/y, and
      occurred mainly during summertime. A complementary river water monitoring
      campaign throughout the country confirmed the above findings. Circumstantial
      evidence points to grassland as a major emission source of FOR and BIO (the main
      compounds in red clover) in surface waters, e.g., their absence in wastewater
      treatment effluents, better correlations of their loads with grassland areas than
      with population equivalents, similar isoflavone ratios in river water and
      grassland runoff. Source apportionment was less clear for DAI, GEN, and equol.
      The contribution of isoflavones to the total estrogenicity of surface waters is
      probably small, except maybe in local rural catchments without major
      anthropogenic activities.

PMID- 19746707
TI  - Hyporheic microbial community development is a sensitive indicator of metal
      contamination.
AB  - Accurate natural resource damage assessment necessitates monitoring organisms or
      communities that respond most sensitively to contaminants. Observational studies
      have demonstrated a correlation between fluvial heavy metal deposition and
      hyporheic microbial community structure. To establish a causal relationship
      between sediment metal content and the structure of colonizing bacterial
      communities, we performed a controlled field experiment River sediments of 1.75
      2.36 mm in diameter with five different contaminant concentrations were collected
      from an environmental metal contamination gradient. Sediments were sterilized and
      then recolonized by incubation in the hyporheic zone of an uncontaminated river
      (i.e., a common garden experiment was performed). A significant correlation
      between hyporheic microbial community structure and heavy metal contamination (R2
      = 0.81) was observed. The abundance of two phylogenetic groups was highly
      correlated with the level of heavy metal contamination (Group I, R2 = 0.96; Group
      III, R2 = 0.96, most closely affiliated with the alpha- and gamma-proteobacteria,
      respectively). Microbial community structural responses were detected at metal
      concentrations an order of magnitude lower than those previously reported to
      impact benthic macroinvertebrate communities. We conclude that hyporheic
      microbial communities could offer the most sensitive method for assessing natural
      resource damage in lotic ecosystems in response to fluvial heavy metal
      deposition.

PMID- 19746708
TI  - Simultaneous nitrogen and phosphorus recovery from sludge-fermentation liquid
      mixture and application of the fermentation liquid to enhance municipal
      wastewater biological nutrient removal.
AB  - Recently, waste activated sludge (WAS) fermentation for short-chain fatty acids
      (SCFAs) production has drawn much attention because the waste biosolids produced
      in wastewater treatment plants (WWTP) can be reused, and the produced SCFAs can
      be applied to promote biological nutrient removal (BNR). Usually, after WAS
      fermentation, the fermentation liquid is separated and then the recovery of
      ammonium and phosphorus, which are released during WAS fermentation, is conducted
      to prevent the increase of nitrogen and phosphorus loadings to WWTP. As an
      alternative to the traditional process, this paper investigated the recovery of
      ammonium and phosphorus in the formation of struvite before sludge-liquid
      separation, and its positive effecton the following sludge-liquid filtration
      separation. First, the conditions for ammonium and phosphorus recovery from the
      WAS fermentation mixture were optimized by response surface methodology (RSM).
      Then, the effect of ammonium and phosphorus recovery on sludge filtration
      dewatering was investigated. With ammonium and phosphorus recovery, it was
      observed that the specific resistance to filtration (SRF), the capillary suction
      time (CST), and the sludge volume after filtration reduced by 96.9, 99.6, and
      88.7%, respectively, compared with no ammonium and phosphorus recovered sludge.
      Third, the mechanisms for ammonium and phosphorus recovery significantly
      enhancing sludge dewatering capacity were investigated. The formation of
      struvite, the neutralization of 5 potential, the increase of magnesium ion, which
      was added during ammonium and phosphorus recovery, and the decrease of sludge
      polymeric substance caused the improvement of sludge dewatering. Finally, the
      fermentation liquid was used as the additional carbon source of BNR, and the
      nutrient removal efficiency was obviously enhanced.

PMID- 19746709
TI  - Role of interlayer hydration in lincomycin sorption by smectite clays.
AB  - Lincomycin, an antibiotic widely administered as a veterinary medicine, is
      frequently detected in water. Little is known about the soil-water distribution
      of lincomycin despite the fact that this is a major determinant of its
      environmental fate and potential for exposure. Cation exchange was found to be
      the primary mechanism responsible for lincomycin sorption by soil clay minerals.
      This was evidenced by pH-dependent sorption, and competition with inorganic
      cations for sorptive sites. As solution pH increased, lincomycin sorption
      decreased. The extent of reduction was consistent with the decrease in cationic
      lincomycin species in solution. The presence of Ca2+ in solution diminished
      lincomycin sorption. Clay interlayer hydration status strongly influenced
      lincomycin adsorption. Smectites with the charge deficit from isomorphic
      substitution in tetrahedral layers (i.e., saponite) manifest a less hydrated
      interlayer environment resulting in greater sorption than that by octahedrally
      substituted clays (i.e., montmorillonite). Strongly hydrated exchangeable cations
      resulted in a more hydrated clay interlayer environment reducing sorption in the
      order of Ca- < K- < Cs-smectite. X-ray diffraction revealed that lincomycin was
      intercalated in smectite clay interlayers. Sorption capacity was limited by clay
      surface area rather than by cation exchange capacity. Smectite interlayer
      hydration was shown to be a major, yet previously unrecognized, factor
      influencing the cation exchange process of lincomycin on aluminosilicate mineral
      surfaces.

PMID- 19746710
TI  - Biogeochemical controls on the corrosion of depleted uranium alloy in subsurface
      soils.
AB  - Military activities have left a legacy of depleted uranium (DU) penetrator waste
      in the near-surface terrestrial environment. To understand the fate of this DU
      alloy, the mechanisms and controlling factors of corrosion need to be determined.
      In this study, field-moist and waterlogged microcosms were used to investigate
      the effect of redox conditions and soil water content on the corrosion and fate
      of DU in subsurface soil, and the impact of corroding DU on the soil microbial
      population. The mechanism of corrosion and the corrosion products formed were
      highly dependent on the water status of the soil. Under field-moist conditions,
      DU corroded at a rate of 0.49 +/- 0.06 g cm(-2) y(-1) and the main U input to
      surrounding soil was large metaschoepite [(UO2)8O2(OH)12 x (H2O)10] particles.
      However, underwaterlogged conditions the rate of corrosion was significantly
      slower at 0.01-0.02 g cm(-2) y(-1) and occurred with the release of dissolved
      species to the surrounding environment. Corrosion ceases under reducing
      conditions, thus redox conditions are important in determining the persistence of
      penetrators in the environment. Corroding DU alters the redox conditions in the
      surrounding environment and both mechanisms of corrosion impact the microbial
      community.

PMID- 19746711
TI  - Reaction mechanism of linuron degradation in TiO2 suspension under visible light
      irradiation with the assistance of H2O2.
AB  - The application of TiO2/H2O/Vis (visible light) process for the aqueous
      degradation of linuron (LNR) has been investigated. The performance of
      TiO/H2O2/Vis process has been compared with other processes such as TiO2/H2O2 in
      the dark, TiO2/Vis, and H2O2 is in terms of LNR decay. The result showed that
      more than 70% LNR could be decomposed in the TiO2/H2O2/Vis. The degradation
      mechanism of LNR by TiO2/H2O2/Vis process has been verified through investigation
      of the effects of various radical scavengers on the performance of this system,
      monitoring the generation of photocurrent, and comparing the intermediates and
      decay pathways of LNR by UV-TiO2 and TiO2/ H2O2/Vis processes with 16 and 17
      intermediates identified, respectively. It has been revealed that demethoxylation
      and demethylation through alkylic-oxidation is the major mechanism of LNR
      degradation while dechlorination (hydroxylation at the chlorine site) and direct
      hydroxylation on the benzene ring is minor in both processes. Mineralization and
      release of chlorine and nitrogen have been also studied.

PMID- 19746712
TI  - Uptake pathways of polycyclic aromatic hydrocarbons in white clover.
AB  - An understanding of the primary pathways of plant uptake of organic pollutants is
      important to enable the risks from crops grown on contaminated soils to be
      assessed. A series of experiments were undertaken to quantify the importance of
      the pathways of contamination and the subsequent transport within the plant using
      white clover plants grown in solution culture. Root uptake was primarily an
      absorption process, but a component of the contamination was a result of the
      transpiration flux to the shoot for higher solubility compounds. The root
      contamination can be easily predicted using a simple relationship with K(OW),
      although if a composition model was used based on lipid content, a significant
      under prediction of the contamination was observed. Shoot uptake was driven by
      the transpiration stream flux which was related to the solubility of the
      individual PAH rather than the K(OW). However, the experiment was over a short
      duration, 6 days, and models based on K(OW) may be better for crops grown in the
      field where the vegetation will approach equilibrium and transpiration cannot
      easily be measured. A significant fraction of the shoot contamination resulted
      from aerial deposition derived from volatilized PAH. This pathway was more
      significant for compounds approaching log K(OA) > 9 and log K(AW) < -3. The shoot
      uptake pathways need further investigation to enable them to be modeled
      separately. There was no evidence of significant systemic transport of the PAH,
      so transfer outside the transpiration stream is likely to be limited.

PMID- 19746713
TI  - Evaluation of a generic multisurface sorption model for inorganic soil
      contaminants.
AB  - The performance of a multisurface sorption model approach, composed of well
      accepted surface complexation models in combination with published "generic"
      parameter sets, is evaluated for its possible use in risk assessment. For that
      purpose, the leaching of a broad range of potential soil contaminants (Ni, Cu,
      Zn, Cd, Pb, Ba, Cr, Co, Mo, V, Sn, Sb, S, As, Se) from eight diffusely and
      industrially contaminated soils is predicted simultaneously without any parameter
      optimization. The model approach includes aqueous speciation in combination with
      sorption to organic matter (NICA-Donnan model), Fe/Al(hydr)oxides (Generalized
      Two-Layer Model), and clay (Donnan model). Independent data generated by pH
      static leaching experiments, performed with individual subsamples over a wide pH
      range (pH 0.4-12), provide a sensitive evaluation of the model performance. Root
      mean-squared error values between predicted and measured log concentrations over
      the entire pH range, RMSE(log), are < 0.5 for Cu, Ni, Cd, Co, S, and Se, and
      RMSE(log) < 1 for Zn, Ba, Cr, Pb, Sn, Mo, Sn and As. The approach without
      parameter optimization has led to recommendations for further research with
      particular emphasis on identification of leaching mechanisms for Pb, Mo, Sb, and
      V and further expansion of the data sets to reduce the uncertainty of the
      available generic sorption parameters for Sn, Sb, Ba, Cr, and V.

PMID- 19746714
TI  - Clay mineral particles as effficient carriers of methylene blue used for
      antimicrobial treatment.
AB  - There is a strong demand to identify new strategies for disinfection and
      treatment of human, animal, and plant pathogens. The presented work shows the
      potential of clay minerals to contribute to the development of novel disinfection
      materials. Enhanced antimicrobial effect of a photoactive organic dye, methylene
      blue (MB), in the colloids of clay mineral was observed. Singlet oxygen (1O2)
      formed upon visible light irradiation was detected directly using luminescence
      measurements atthe near-infrared region and by spin-trapping method. While MB
      adsorbed on clay colloid particles lost the ability to produce 1O2 due to
      molecular aggregation, surprisingly, the antimicrobial activity was significantly
      enhanced. Under visible light irradiation, MB/clay minerals dispersions prevented
      the sporulation of A. niger and Penicillium sp. and inhibited the growth of C.
      albicans by an additional 6-15% when compared with MB solution. In the
      experiments with E. coli, the efficiency of MB was increased by the reduction of
      surviving cells by 27 and 33%. S. aureus proved to be the most susceptible to
      MB/clay dispersions. Only less than 20% cells survived with respect to the
      control experiment at the low MB concentration (1.1 x 10(-6) mol dm(-3)). The
      contradiction between the significant antimicrobial properties of MB in clay
      colloidal systems and low 1O2 formation can be explained in terms of the
      photosensitization mechanism. The role of clay particles is most likely to
      promote the contact between microorganism cells and photoactive MB. Although the
      dye directly bound to the clay surface exhibits significantly reduced
      photoactivity, the presence of clay mediates the delivery of dye molecules on the
      surface or inside cells. The results indicate new perspectives of potential
      implementations of clay minerals as parts of complex disinfection materials for
      industrial applications or in understanding similar processes in nature.

PMID- 19746715
TI  - Evaluation of the oxidation of organic compounds by aqueous suspensions of
      photosensitized hydroxylated-C60 fullerene aggregates.
AB  - Ultraviolet (UV) irradiated polyhydroxylated fullerene (fullerol) nanomaterials
      are examined for their potential to degrade organic compounds via reactive oxygen
      species (ROS) mediated by a photosensitization process. Organic compounds were
      selected for their sensitivity to individual species of reactive oxygen (hydroxyl
      radical (*OH-) for degradation of salicylic acid (SA); singlet oxygen (1O2) for
      degradation of 2-chlorophenol (2CP), and superoxide (O2*-) for oxidation of
      ethanol) and were monitored over time in aqueous suspensions of fullerol
      aggregates. Only the 2CP showed significant degradation underscoring the
      specificity of the fullerol in producing singlet oxygen in these conditions.
      Monitoring these processes via high performance liquid chromatography (HPLC)
      confirmed that organic compounds degraded primarily by ROS over a range of
      fullerol concentrations, pH values, and temperatures.

PMID- 19746716
TI  - Sorption and competition of aromatic compounds and humic acid on multiwalled
      carbon nanotubes.
AB  - Sorption of humic acid (HA) and aromatic compounds by multiwalled carbon
      nanotubes (MWCNTs), and their competition on MWCNTs were examined. HA sorption by
      MWCNTs was regulated by their surface area (SA). Hydrophobic and pi-pi
      attractions of HA with MWCNTs were main driving forces for their interactions.
      K(d)/K(ow) values of phenanthrene (Phen), naphthalene (Naph), and 1-naphthol(1
      Naph) by individual MWCNTs were positively correlated with their molecular size,
      suggesting that micropore-filling could not be a predominant mechanism. HA had
      the lowest competition with Phen and 1-Naph on MWCNT20, due to its greatest
      abundance of sorption sites. Competition between HA and 1-Naph followed an order
      MWCNT40 < MWCNT60 < MWCNT100, due to their reduction in SA and porosity.
      Micropore blockage and direct competition by HA increased with deceasing SA and
      porosity of MWCNTs. MWCNT20 had much more sorption sites than other MWCNTs,
      leading to insignificant difference in competition between 1-Naph and Phen with
      HA. Also, HA had higher competition with Phen on MWCNT40, MWCNT60, and MWCNT100
      than 1-Naph. Our results highlight the significance of MWCNT SA for HA sorption
      and the associated influence on sorption of aromatic compounds. Further,
      molecular size and hydrophobicity of aromatic compounds strongly affected their
      competition with HA on MWCNTs.

PMID- 19746717
TI  - Development of a group contribution method to predict aqueous phase hydroxyl
      radical (HO*) reaction rate constants.
AB  - The hydroxyl radical (HO*) is a strong oxidant that reacts with electron-rich
      sites of organic compounds and initiates complex chain mechanisms. In order to
      help understand the reaction mechanisms, a rule-based model was previously
      developed to predict the reaction pathways. For a kinetic model, there is a need
      to develop a rate constant estimator that predicts the rate constants for a
      variety of organic compounds. In this study, a group contribution method (GCM) is
      developed to predict the aqueous phase HO* rate constants for the following
      reaction mechanisms: (1) H-atom abstraction, (2) HO* addition to alkenes, (3) HO*
      addition to aromatic compounds, and (4) HO* interaction with sulfur (S)-,
      nitrogen (N)-, or phosphorus (P)-atom-containing compounds. The GCM hypothesizes
      that an observed experimental rate constant for a given organic compound is the
      combined rate of all elementary reactions involving HO*, which can be estimated
      using the Arrhenius activation energy, E(a), and temperature. Each E(a) for those
      elementary reactions can be comprised of two parts: (1) a base part that includes
      a reactive bond in each reaction mechanism and (2) contributions from its
      neighboring functional groups. The GCM includes 66 group rate constants and 80
      group contribution factors, which characterize each HO* reaction mechanism with
      steric effects of the chemical structure groups and impacts of the neighboring
      functional groups, respectively. Literature-reported experimental HO* rate
      constants for 310 and 124 compounds were used for calibration and prediction,
      respectively. The genetic algorithms were used to determine the group rate
      constants and group contribution factors. The group contribution factors for H
      atom abstraction and HO* addition to the aromatic compounds were found to
      linearly correlate with the Taft constants, sigma*, and electrophilic substituent
      parameters, sigma+, respectively. The best calibrations for 83% (257 rate
      constants) and predictions for 62% (77 rate constants) of the rate constants were
      within 0.5-2 times the experimental values. This accuracy may be acceptable for
      model predictions of the advanced oxidation processes (AOPs) performance,
      depending on how sensitive the model is to the rate constants.

PMID- 19746718
TI  - Characterizing dissolved organic matter using PARAFAC modeling of fluorescence
      spectroscopy: a comparison of two models.
AB  - We evaluated whether fitting fluorescence excitation-emission matrices (EEMs) to
      a previously validated PARAFAC model is an acceptable alternative to building an
      original model. To do this, we built a 10-component model using 307 EEMs
      collected from southeast Alaskan soil and streamwater. All 307 EEMs were then fit
      to the existing model (CM) presented in Cory and McKnight (Environ. Sci. Technol.
      2005, 39, 8142-8149). The first approach for evaluating whether the EEMs were fit
      well to the CM model was an evaluation of the residual EEMs, and we found 22 EEMs
      were fit poorly by the CM model. Our second measure for verifying whether EEMs
      were fit well to the CM model was a comparison of correlations between the
      percent contribution of PARAFAC components and DOM measurements (e.g., dissolved
      nutrient concentrations), and we found no significant difference Ip > 0.05)
      between the two models. These results support the approach of fitting EEMs to an
      existing model when DOM is collected from similar environments, which can
      potentially reduce some of the problems when building an original PARAFAC model.
      However, it is important to recognize that some of the sensitivity or ecological
      interpretative power may be lost when fitting EEMs to an existing model.

PMID- 19746719
TI  - Testing and application of surrogate surfaces for understanding potential gaseous
      oxidized mercury dry deposition.
AB  - Currently there is no standard method for measurement of atmospheric mercury dry
      deposition. While all operationally defined forms of atmospheric mercury
      (elemental, oxidized, and particulate) can be dry deposited, oxidized forms are
      of concern due to high deposition velocities, water solubility, and reactivity.
      This paper describes the development of a surrogate surface for characterizing
      potential dry deposition of gaseous oxidized mercury (GOM). Laboratory tests
      showed that the surface collected HgCl2, HgBr2, and HgO with equal efficiency,
      and deposition was not significantly influenced by temperature, humidity, or
      ozone concentrations. Deposition of mercury to surfaces in field deployments was
      correlated with GOM concentrations (r2 = 0.84, p < 0.01, n = 326. Weekly mean GOM
      deposition velocities from surface deployments (1.1 +/- 0.6 cm s(-1)) were higher
      than modeled values (0.4 +/- 0.2 cm s(-1)) at four field sites, but were within
      the range reported for direct measurements. Although the surfaces do not simulate
      the heterogeneity of natural surfaces and need to be validated by direct
      measurements, they do provide a physical means for estimating temporal trends and
      spatial variability of dry deposition of GOM.

PMID- 19746720
TI  - Applying surrogates and indicators to assess removal efficiency of trace organic
      chemicals during chemical oxidation of wastewaters.
AB  - To respond to concerns associated with wastewater-derived contaminants water
      utilities are looking for new approaches for monitoring trace organic chemicals
      in conventional and advanced water treatment processes. This study examines the
      use of a combination of surrogate parameters and indicator compounds tailored to
      monitor the removal efficiency of advanced oxidation processes employed by
      treatment plants engaged in indirect potable water reuse programs. Potential
      surrogate parameters and indicator compounds, identified by reviewing previous
      publications and classified by their structural properties, were tested in pilot-
      and full-scale treatment systems. Dilantin, DEET, meprobamate, and iopromide are
      good indicators to assess optimized oxidation conditions while ozonating tertiary
      treated wastewaters. UVA reduction, ozone byproduct formation, such as simple
      organic acids, and ozone exposure correlated with "sweet spot" compounds, where
      ozone exposure correlated with trace organic removal across five tertiary-treated
      wastewaters. Findings indicate that the proposed framework can serve as a
      conservative monitoring approach for advanced oxidation processes as well as
      other indirect potable reuse processes to ensure proper removal of identified and
      unidentified wastewater-derived organic contaminants, to detect failures in
      system performance, and is protective of public health.

PMID- 19746721
TI  - Use of quantitative and conventional PCR to assess biodegradation of bovine and
      plant DNA during cattle mortality composting.
AB  - Understanding mortality composting requires assessing the biodegradation efficacy
      of carcasses and other materials of animal and plant origin. Biosecure (plastic
      wrapped) compost structures were built containing 16 cattle carcasses placed on
      40 cm straw and covered with 160-cm of feedlot manure. Compost was collected from
      depths of 80 and 160 cm (P80, P160) and DNA degradation assessed over 147 days of
      static composting, and during 180 days of active composting. Residual soft
      tissues from carcasses were collected on day 147. At P80, copies of a 171-bp
      bovine mitochondrial DNA (Mt171) and 138-bp plant Rubisco gene fragment (Rub138)
      were reduced compared to initial copy numbers (CN) by 79% and 99% after 147 days,
      respectively. At P160, Mt171, and Rub138 decreased compared to initial CN by 20%
      and 99% by day 147, respectively. After 327 days, degradation of Mt171 increased
      to 91% compared to initial CN. Compared to fresh tissues, residual tissues at day
      147 had a 99% reduction in genomic DNA yield. Yield of DNA was related to copies
      of a 760-bp bovine mitochondrial fragment (Mt760) which were > 93% reduced at
      both P80 and P160 after 147 day. Secondary composting improved decomposition of
      bovine tissues and Mt760 was not detectable after 207 days. A 99% reduction in
      genomic DNA of composted tissue and > 93% reduction of Mt760 suggests almost
      complete decomposition of carcass soft tissue after 147 days.

PMID- 19746722
TI  - Fate of carbamazepine during water treatment.
AB  - Seven transformation products of carbamazepine generated by at least one of three
      common water treatment technologies (UV-radiation, oxidation with chlorine
      dioxide (ClO2), and biological treatment with activated sludge) were identified
      by complementary use of ion trap, single quadrupole, and quadrupole-time-of
      flight mass spectrometers. Acridine was formed during all of the three treatment
      processes, while acridine 9-carbaldehyde was identified as an intermediate during
      ClO2 oxidation. Further treatment of acridine with ClO2 produced 9-hydroxy
      acridine. UV-treatment resulted in the formation of acridone, hydroxy-(9H,10H)
      acridine-9-carbaldehyde, acridone-N-carbaldehyde, and 1-(2-benzaldehyde)-(1H,3H)
      quinazoline-2,4-dione, while biological breakdown of acridine yielded acridone.
      In parallel, the transformation product iminostilbene was observed during sample
      analysis. In addition, this study compared the treatment technologies according
      to the removal of carbamazepine and the production and decay of its
      transformation products. The most successful method for the removal of
      carbamazepine was UV treatment while acridine and acridone were more susceptible
      to biological treatment. Therefore, based on the enhanced biodegradability of
      carbamazepine residues achieved by UV irradiation, we propose a coupled treatment
      technology involving an initial UV treatment step followed by biological
      treatment which may satisfactorily remove the parent compound and its
      transformation products.

PMID- 19746723
TI  - Ultra-trace determination of phthalate ester metabolites in seawater, sediments,
      and biota from an urbanized marine inlet by LC/ESI-MS/MS.
AB  - This study presents results of an analytical method developed for the
      quantification of monoalkyl phthalate esters (MPEs) in seawater, sediments, and
      biota. The method uses accelerated solvent extraction, solid-phase extraction,
      and liquid chromatography electrospray ionization tandem mass spectrometry (LC/
      ESI-MS/MS). Results show the method is robust and can provide trace measurement
      of several MPE analytes at low parts per trillion levels in water and low parts
      per billion levels in sediments and biological tissues. Analyte recoveries varied
      between 70% and 110%. Method detection limits (MDLs) varied between 0.19 and 3.98
      ng/L in seawater and between 0.024 and 0.99 ng/g in sediment and biota, which is
      approximately 10-50 times lower than previously reported MDLs using gas
      chromatography mass spectrometry. We applied the method to field collected
      samples of seawater, sediments, and tissues of mussels, crabs, and fish from
      False Creek an urbanized marine inlet near Vancouver, Canada. The results
      indicate residues of several MPEs can be found in surface waters, sediments, and
      organism tissues of this marine system. Monoethyl phthalate (MEP), mono-n-butyl
      phthalate (MnBP), and mono-(2-ethylhexyl)-phthalate (MEHP) were frequently
      detected in all matrices. MnBP generally exhibited the highest concentrations
      among MPEs analyzed. Detectable concentrations of MPEs varied from 1 to 600 ng/L
      in seawater, 0.1 to 20 ng/g dry wt in sediments, and 0.1 to 600 ng/g wet wt in
      biota. Observed concentrations of low molecular weight MPEs in mussels were found
      to be significantly higher (P < 0.05) than those of corresponding parent DPEs
      (e.g., MnBP > DBP). Mono-iso-nonyl-phthalate (MoC9) and mono-iso-decyl phthalate
      (MoC10), which were routinely detected in water and sediments, were not detected
      in False Creek biota, indicating negligible uptake and/or in vivo bioformation of
      these high molecular weight MPEs. The ability to measure MPEs in complex
      environmental samples provided by this LC/ESI-MS/MS method expands the capability
      for future biomonitoring and risk assessment of phthalate plasticizers.

PMID- 19746724
TI  - Reduction of fine particle emissions from wood combustion with optimized
      condensing heat exchangers.
AB  - In this study, we designed and built a condensing heat exchanger capable of
      simultaneous fine particle emission reduction and waste heat recovery. The
      deposition mechanisms inside the heat exchanger prototype were maximized using a
      computer model which was later compared to actual measurements. The main
      deposition mechanisms were diffusio- and thermophoresis which have previously
      been examined in similar conditions only separately. The obtained removal
      efficiency in the experiments was measured in the total number concentration and
      ranged between 26 and 40% for the given pellet stove and the heat exchanger. Size
      distributions and number concentrations were measured with a TSI Fast mobility
      particle sizer (FMPS). The computer model predicts that there exists a specific
      upper limit for thermo- and diffusiophoretic deposition for each temperature and
      water vapor concentration in the flue gas.

PMID- 19746725
TI  - Ozonolysis of lignin models in aqueous solution: anisole, 1,2-dimethoxybenzene,
      1,4-dimethoxybenzene, and 1,3,5-trimethoxybenzene.
AB  - The lignin models anisole, 1,2-dimethoxybenzene, 1,4-dimethoxybenzene, and 1,3,5
      trimethoxybenzene were reacted with ozone in aqueous solution, and major products
      were identified and quantified with respect to ozone consumption when reference
      material was available. Hydroxylation products in yields equivalent to those of
      singlet oxygen and muconic products (in analogy to the Criegee mechanism)
      dominate. The formation of quinones points to the release of methanol. Hydroxyl
      radicals (*OH, quantified, main precursor: O3*-), singlet oxygen (quantified),
      O2*- radicals (quantified), and as counterparts of the *OH radicals radical
      cations of these methoxybenzenes must each play an important role as
      intermediates. In the case of 1,4-dimethoxybenzene, for example, the following
      products were identified (yields in parentheses when quantified): methyl(2Z,4E-4
      methoxy-6-oxo-hexa-2,4-dienoate 5 (52%), hydroquinone 6 (2%), 1,4-benzoquinone 7
      (8%), 2,5-dimethoxyhydroquinone 8,2,5-dimethoxy-1,4-benzoquinone 9, singlet
      oxygen (6%), hydrogen peroxide (56%), *OH (approximately 17%), O2*- (< or = 9%).
      Gibbs energies for the various potential reaction pathways were calculated with
      the help of the Jaguar 7.5 program.

PMID- 19746726
TI  - Enhanced mixing and plume containment in porous media under time-dependent
      oscillatory flow.
AB  - Solute transport experiments were conducted in a decimeter scale flow cell packed
      with sand to study the potential for enhanced mixing of solutes in porous media
      and improved containment of injected plumes under multiple pumping-well driven,
      time-dependent oscillatory flow with respect to constant flow. Real-time imaging
      of the colorimetric reaction of Tiron (1,2-dihydroxybenzene-3,5-disulfonic acid)
      and molybdate was used to quantify mixing, whereas fluorescein was used to better
      examine plume size. Results from the small scale experiments clearly demonstrated
      the enhanced mixing of solutes under low Reynolds number oscillatory flow (a
      factor of 2 with respect to constant flow in homogeneous sand and a factor of 3
      in layered sand), as the result of increased contact interface for solute
      diffusion. Further, the injected solute plume was better contained under
      oscillatory flow (25% less area with respect to constant flow in homogeneous
      sand) due to the cancellation of advective transport at each well over time.
      Enhanced mixing under oscillatory flow may enhance the processes of chemical and
      biological remediation. Furthermore, improved plume containment under oscillatory
      flow may require smaller amounts of chemicals to be injected during aquifer
      remediation.

PMID- 19746727
TI  - Cu-TiO2/Ti dual rotating disk photocatalytic (PC) reactor: dual electrode
      degradation facilitated by spontaneous electron transfer.
AB  - A Cu-TiO2/Ti dual rotating disk photocatalytic (PC) reactor has been developed
      based on our single rotating disk photoelectrocatalytic (PEC) reactor (Y. Xu, et
      al, Environ. Sci. Technol. 2008, 42, 2612-2617), and successfully applied to the
      treatment of laboratory and industrial dye wastewater. Round TiO2/Ti and Cu disks
      of the same size are connected by a Cu wire and fixed parallel on an axis
      continually rotating at 90 rpm. High treatment efficiency is obtained due to
      direct photooxidation on the TiO2/Ti photoanode as well as additional degradation
      on the Cu cathode, which is speculated via indirect hydrogen peroxide (H2O2)
      oxidation and direct electro-reduction of dye on cathode. The mechanism of the Cu
      TiO2/Ti dual rotating disk PC reactor was investigated. In a 20 mg L(-1)
      Rhodamine B (RB) solution, approximately 100 mV of potential and 10 microA of
      current were measured between the Cu and TiO2/Ti electrode during PC treatment.
      Such phenomenon was explained by spontaneous electron transfer based on the same
      principle of establishing a Schottky barrier. On the Cu electrode surface, the
      photoelectrons either reduced dye molecules directly or reacted with dissolved
      oxygen (DO) to form H2O2. Rotation of electrodes out of the solution enhanced the
      mass transfer of target compound and kept the aqueous film fresh. The Cu-TiO2/ Ti
      dual rotating disk PC reactor is a simple and effective device for the treatment
      of RB dye wastewater.

PMID- 19746728
TI  - Effect of groundwater iron and phosphate on the efficacy of arsenic removal by
      iron-amended BioSand filters.
AB  - Naturally occurring arsenic in groundwater in Cambodia is a serious health
      concern. This study tested the efficacy of a BioSand filter amended with iron
      nails, Kanchan filter, as a household water treatment option with three natural
      arsenic-bearing groundwater sources of varying compositions and spiked with lab
      cultured E. coli and MS2. The effectiveness of arsenic and pathogen removal was
      not constant over time and was highly dependent on the influent composition. The
      filter was relatively ineffective in treating arsenic contaminated groundwater
      and effluent arsenic concentrations were between 74 and 2206 microg L(-1), which
      is higher than accepted drinkng water standards. The overall average arsenic
      removal was 39.4, 74.9, and 45.4%, respectively, and the extent of arsenic
      removal was not related to the influent arsenic concentration. The main reasons
      for poor arsenic removal was due to the combination of high influent P (> 0.5 mg
      L(-1)) and low Fe (< 5 mg L(-1)) concentrations and that the added iron nails
      were largely ineffective due to insufficient contact time withthe water. The
      findings suggest that such amended filters should not be widely deployed until
      improvements are made to address the consistency and efficacy of treatment In
      addition, the filter poses some potential health risk associated with the
      production of elevated nitrate levels in the effluent within the filter, possibly
      due to nitrification and high levels of ammonia in the groundwater.

PMID- 19746729
TI  - Electrolytic redox and electrochemical generated alkaline hydrolysis of hexahydro
      1,3,5-trinitro-1,3,5 triazine (RDX) in sand columns.
AB  - Sand-packed horizontal flow columns (5 cm i.d. x 65 cm)l were used in laboratory
      experiments to simulate in situ electrolytic and alkaline hybrid treatment zone
      for aqueous phase decomposition of RDX. An upgradient cathode and downgradient
      anode, spaced 35 cm apart were used to create alkaline reducing conditions
      followed by oxic, acidic conditions to degrade RDX by combination of alkaline
      hydrolysis and direct electrolysis. A preliminary experiment (25 mg/L RDX
      influent) with seepage velocity of 30.5 cm/day and current density of 9.9 A/m2
      was used to determine the treatment feasibility and the aqueous products of RDX
      decomposition. Three additional column experiments (0.5 mg/L RDX influent) under
      the same conditions as the preliminary column were used to observe the treatment
      process repeatability and the alkaline treatment zone development. The results
      demonstrated approximately 95% decomposition of RDX in the column with an applied
      current density of 9.9 A/m2. Aqueous end-products formate, nitrite, and nitrate
      were detected in the effluent. Approximately 75% of the RDX was destroyed near
      the cathode, presumably by electrolysis, with 23% decomposed downstream of the
      cathode by alkaline hydrolysis. The preliminary column pseudo first order
      alkaline hydrolysis rate coefficient of 10.7 x 10(-3) min(-1) was used to
      estimate a treatment zone length less than 100 cm for RDX treatment below the EPA
      drinking water lifetime health advisory of 0.002 mg/L.

PMID- 19746730
TI  - Increasing sulfur supply enhances tolerance to arsenic and its accumulation in
      Hydrilla verticillata (Lf.) Royle.
AB  - The present study was aimed to analyze the effects of variable S supply on
      arsenic (As) accumulation potential of Hydrilla verticillata (Lf.) Royle. Plants
      were exposed to either arsenate (AsV; 50 microM) or arsenite (AsIII; 5 microM)
      for 4 h and 1 day while S supply was varied as deficient (2 microM, -S), normal
      (1 mM, +S) and excess (2 mM, +HS). The level of As accumulation (microg g(-1) dw)
      after 1 day was about 2-fold higher upon exposure to either AsV (30) or AsIII
      (50) in +HS plants than that being in +S (12 and 24) and -S (14 and 26) plants.
      The +HS plants showed a significant stimulation of the thiol metabolism upon As
      exposure. Besides, they did not experience significant toxicity, measured in
      terms of malondialdehyde accumulation; an indicator of oxidative stress. By
      contrast, -S plants suffered from oxidative stress probably due to negative
      impact to thiol metabolism. Variable S supply also modulated the activity of
      enzymes of glycine and serine biosynthesis indicating an interconnection between
      S and N metabolism. In conclusion, an improved supply of S to plants was found to
      augment their ability for As accumulation through stimulated thiol metabolism.

PMID- 19746731
TI  - Reaction mechanisms for enhancing mineral sequestration of CO2.
AB  - Storage of CO2 through mineral sequestration using olivine has been shown to
      produce environmentally benign carbonates. However, due to the formation of a
      rate-limiting reaction product layer, the rate of reaction is insufficient for
      large-scale applications. We report the results of altering the reactant solution
      composition and the resultant reaction mechanism to enhance the reaction rate.
      The products were analyzed for total carbon content with thermal decomposition
      analysis, product phase compositions with Debye-Scherrer X-ray powder diffraction
      (XRD), surface morphology with scanning electron microscopy (SEM), and
      composition with energy dispersive X-ray spectroscopy (EDXS). Carbon analysis
      showed that an increase in bicarbonate ion activity increased the olivine to
      carbonate conversion rate. The fastest conversion rate, 63% conversion in one
      hour, occurred in a solution of 5.5 M KHCO3. Additionally, SEM confirmed that
      when the bicarbonate ion activity was increased, magnesium carbonate product
      particles significantly increased in both number density and size and the rate
      passivating-reaction layer exfoliation was augmented.

PMID- 19746732
TI  - Linking material flow analysis and resource policy via future scenarios of in-use
      stock: an example for copper.
AB  - A key aspect to achieving long-term resource sustainability is the development of
      methodologies that explore future material cycles and their environmental impact.
      Using a novel dynamic in-use stock model and scenario analysis, I analyzed the
      multilevel global copper cycle over the next 100 years. In 1990, the
      industrialized world had an in-use copper stock about twice as large as the
      developing world and a per capita in-use stock of about six times as large. By
      2100, the developing world will have an in-use copper stock about three times as
      large as the industrialized world, but the industrialized world will maintain a
      per capita stock twice that of the developing world. Under a scenario of no
      material substitution or technological change in copper products, global in-use
      stock in 2100 will be about as large as currently known copper resources.
      However, current scrap recycling trends and exploration will alleviate absolute
      supply pressure but not environmental impacts from decreasing copper are grades.
      Additionally, unexpected emergent properties of dematerialization are observed
      from the in-use stock model that arise solely from the properties of stock
      dynamics, an infrequently discussed cause of dematerialization in the literature.

PMID- 19746733
TI  - Survey of the potential environmental and health impacts in the immediate
      aftermath of the coal ash spill in Kingston, Tennessee.
AB  - An investigation of the potential environmental and health impacts in the
      immediate aftermath of one of the largest coal ash spills in U.S. history at the
      Tennessee Valley Authority (TVA) Kingston coal-burning power plant has revealed
      three major findings. First the surface release of coal ash with high levels of
      toxic elements (As = 75 mg/kg; Hg = 150 microg/kg) and radioactivity (226Ra +
      228Ra = 8 pCi/g) to the environment has the potential to generate resuspended
      ambient fine particles (< 10 microm) containing these toxics into the atmosphere
      that may pose a health risk to local communities. Second, leaching of
      contaminants from the coal ash caused contamination of surface waters in areas of
      restricted water exchange, but only trace levels were found in the downstream
      Emory and Clinch Rivers due to river dilution. Third, the accumulation of Hg- and
      As-rich coal ash in river sediments has the potential to have an impact on the
      ecological system in the downstream rivers by fish poisoning and methylmercury
      formation in anaerobic river sediments.

PMID- 19746734
TI  - Chemical characteristics and oxidative potential of particulate matter emissions
      from gasoline, diesel, and biodiesel cars.
AB  - Three light-duty vehicles in five different configurations [a Honda Accord
      operating with diesel with a closed-coupled oxidation catalyst and an underfloor
      catalyst replaced in some tests with a diesel particle filter (DPF), a Toyota
      Corolla operating with gasoline, and a VW Golf alternatively operating with
      petrodiesel or biodiesel] were tested in a dynamometer facility to develop an
      improved understanding of the factors affecting the toxicity of particulate
      exhaust emissions. The vehicles were tested using a variety of real-world driving
      cycles, more than the certification test (New European Driving Cycle). Particle
      samples were collected and analyzed for elemental and organic carbon (EC and OC,
      respectively), water soluble and water insoluble organic carbon (WSOC and WISOC,
      respectively), and inorganic ions, and the emission rates (mg/km) for each
      vehicle/configuration were determined. A dithiothreitol (DTT) assay was used to
      assess the oxidative potential of the particulate matter (PM) samples. The DPF
      equipped diesel and gasoline vehicles were characterized by the lowest overall PM
      mass emissions, while the diesel and biodiesel cars produced the most potent
      exhaust in terms of oxidative activity. When the DPF was fitted on the Honda
      Accord diesel vehicle, the mass emission rates and distance-based oxidative
      potential were both decreased by 98%, compared to the original configuration.
      Correlation analysis showed that the DTT consumption rate was highly associated
      with WSOC, WISOC, and OC (R = 0.98, 0.93, and 0.94, respectively), consistent
      with previous findings.

PMID- 19746735
TI  - Hepatic transcriptomic and metabolomic responses in the stickleback (Gasterosteus
      aculeatus) exposed to environmentally relevant concentrations of
      dibenzanthracene.
AB  - A three-spined stickleback (Gasterosteus aculeatus) cDNA array and one
      dimensional 1H nuclear magnetic resonance (NMR) spectroscopy-based metabolomics
      approach, together with individual biomarkers,were employed to investigate the
      responses of male sticklebacks to polycyclic aromatic hydrocarbon exposure. Fish
      were exposed to 1,2:5,6-dibenzanthracene (DbA) at concentrations between 0.01 and
      50 microg per liter dissolved in the ambient water for four days, and hepatic
      transcript and metabolite profiles were determined in comparison with those of
      solvent-exposed controls. Induction of gene expression was apparent for
      cytochrome P450 1A (CYP1A) and CYP2-family monooxygenases and these responses
      were strongly correlated with DbA exposure concentrations (for CYP1A r > 0.996).
      Expression of suites of genes related to bile acid biosynthesis, steroid
      metabolism, and endocrine function were also affected, as demonstrated by gene
      ontology analyses. Expression changes in selected genes were confirmed by real
      time PCR. Metabolomics highlighted notable changes in concentrations of taurine,
      malonate, glutamate, and alanine. These statistically significant responses to
      environmentally relevant concentrations of DbA at the transcriptomic and
      metabolomic levels provided sensitive markers characteristic of environmentally
      relevant low-level DbA exposure. Metabolic pathways were identified where both
      gene expression and metabolite concentrations were altered in response to DbA.

PMID- 19746736
TI  - Toxicity and developmental defects of different sizes and shape nickel
      nanoparticles in zebrafish.
AB  - Metallic nanoparticles such as nickel are used in catalytic sensing, and
      electronic applications, but health and environmental affects have not been fully
      investigated. While some metal nanoparticles result in toxicity, it is also
      important to determine whether nanoparticles of the same metal but of different
      size and shape changes toxicity. Three different size nickel nanoparticle (Ni
      NPs) of 30, 60, and 100 nm and larger particle clusters of aggregated 60 nm
      entities with a dendritic structure were synthesized and exposed to zebrafish
      embryos assessing mortality and developmental defects. Ni NPs exposure was
      compared to soluble nickel salts. All three 30, 60, and 100 nm Ni NPs are equal
      to or less toxic than soluble nickel while dendritic clusters were more toxic.
      With each Ni NP exposure, thinning of the intestinal epithelium first occurs
      around the LD10 continuing into the LD50. LD50 exposure also results in skeletal
      muscle fiber separation. Exposure to soluble nickel does not cause intestinal
      defects while skeletal muscle separation occurs at concentrations well over LD50.
      These results suggest that configuration of nanoparticles may affect toxicity
      more than size and defects from Ni NPs exposure occur by different biological
      mechanisms than soluble nickel.

PMID- 19746737
TI  - Differential toxicity of carbon nanomaterials in Drosophila: larval dietary
      uptake is benign, but adult exposure causes locomotor impairment and mortality.
AB  - Rapid growth in nanomaterial manufacturing is raising concerns about potential
      adverse effects on the environment. Nanoparticle contact with intact organisms in
      the wild may lead to different biological responses than those observed in
      laboratory cell-based toxicity assays. In nature, the scale and chemistry of
      nanoparticles coupled with the surface properties, texture, and behaviors of the
      organisms will influence biologically significant exposure and ultimate toxicity.
      We used larval and adult Drosophila melanogaster to study the effects of carbon
      nanomaterial exposure under several different scenarios. Dietary uptake of
      fullerene C60, carbon black (CB), or single-walled or multiwalled nanotubes
      (SWNTs, MWNTs) delivered through the food to the larval stage had no detectable
      effect on egg to adult survivorship, despite evidence that the nanomaterials are
      taken up and become sequestered in tissue. However, when these same nanocarbons
      were exposed in dry form to adults, some materials (CB, SWNTs) adhered
      extensively to fly surfaces, overwhelmed natural grooming mechanisms, and led to
      impaired locomotor function and mortality. Others (C60, MWNT arrays) adhered
      weakly, could be removed by grooming, and did not reduce locomotor function or
      survivorship. Evidence is presented that these differences are primarily due to
      differences in nanomaterial superstructure, or aggregation state, and that the
      combination of adhesion and grooming can lead to active fly borne nanoparticle
      transport.

PMID- 19746738
TI  - Exposure to persistent organic pollutants and first-year survival probability in
      gray seal pups.
AB  - Many studies have demonstrated that persistent organic pollutants are transferred
      from mother to pup during lactation in phocid seals, but none have been able to
      determine the significance of these findings for survivorship. The aim of this
      study was to investigate the relationship between blubber contaminant
      concentrations and first-year survival in gray seal pups. A mark-recapture
      framework was used to estimate survival probabilities and animals were "marked"
      using novel mobile phone tags. Individual and group covariates (sex, condition,
      and blubber contaminants) were embedded within a live-resighting model. The most
      significant covariates remained condition at weaning and sex (males in poor
      condition had the lowest survival probability), as was found previously, but
      there was also evidence indicating that higher blubber contaminants additionally
      decreased survivorship. The models' Akaike's Information Criteria (AICs) and
      their associated weights, point toward the tetrapolybrominated diphenyl ether
      congeners (dominated by BDE-47) as being the most important group of contaminants
      affecting survival probability, followed by the total
      dichlorodiphenyltrichloroethanes (DDTs) and pentapolychlorinated biphenyl
      congeners. These compounds were not the most abundant in the blubber, suggesting
      further studies into their toxicological effects in this species are necessary.
      The specific mechanisms driving the reduction in survivorship remain unknown.

PMID- 19746739
TI  - Effect of occupational exposure to multiple pesticides on translocation yield and
      chromosomal aberrations in lymphocytes of plant workers.
AB  - Employees handling pesticides are simultaneously exposed to different active
      substances. Occurring multiple chemical exposures may pose a higher risk than it
      could be deduced from studies evaluating the effect of a single substance. This
      study comprised 32 pesticide plantworkers exposed to carbofuran, chlorpyrifos,
      metalaxyl, and dodine and an equal number of control subjects. Groups were
      matched by age (43.8 +/- 10.16 vs 41.8 +/- 7.42, respectively), sex (14 females;
      18 males), and smoking (11 smokers; 21 nonsmokers). Chromosome aberration and
      translocation frequencies were determined using a standard aberration assay and
      fluorescent in situ hybridization (FISH) by applying painting probes for
      chromosomes 1, 2, and 4. Although significant, an observed increase in chromatid
      breaks (5.2 +/- 2.49) compared to controls (2.1 +/- 0.87), p(PostHoc) = 0.000001
      is biologically irrelevant. Genomic frequency of translocations was also
      significantly elevated (exposed 0.0165 +/- 0.0070; control 0.0051 +/- 0.0023,
      P(PostHoc) = 0.000004). The distribution of translocations among chromosomes 1,
      2, and 4 did not differ from control subjects. It corresponded to the
      distribution of DNA content among selected chromosomes indicating randomness of
      DNA damage. A good translocation yield correlation within years spent in
      pesticide production indicates that multiple pesticide exposure may pose a risk
      to genome integrity. However, for more accurate health risk assessments, the use
      of probes for some other groups of chromosomes should be considered.

PMID- 19746740
TI  - Comparative toxicity of C60 aggregates toward mammalian cells: role of
      tetrahydrofuran (THF) decomposition.
AB  - C60 fullerene is a promising material because of its unique physiochemical
      properties. However, previous studies have reported that colloidal aggregates of
      C60 (nC60) produce toxicity in fish and human cell cultures. The preparation
      method of nC60 raises questions as to whether the observed effects stem from
      fullerenes or from the organic solvents used during the preparation of the
      suspensions. In this paper, we set out to elucidate the mechanism by which
      tetrahydrofuran (THF) treatment to enhance the preparation of nC60 leads to
      cytotoxicity in a mouse macrophage cell line. Our results demonstrate that
      THF/nC60 but not fullerol or aqueous nC60 generates cellular toxicity through a
      pathway that involves increased intracellular flux and mitochondrial perturbation
      in RAW 264.7 cells. Interestingly, the supernatant of the THF/n60 suspension
      rather than the colloidal fullerene aggregates mimics the cytotoxic effects due
      to the presence of gamma-butyrolactone and formic acid. Thus, the role of nC60 in
      the cellular responses is likely not due to the direct effect of the nC60
      material surface on the cells but is related to the conversion of THF into a
      toxic byproduct during preparation of the suspension.

PMID- 19746741
TI  - Adhesion and enrichment of metals on human hands from contaminated soil at an
      Arctic urban brownfield.
AB  - Human exposure to contaminated soils drives clean up criteria at many urban
      brownfields. Current risk assessment guidelines assume that humans ingest some
      fraction of soil smaller than 4 mm but have no estimates of what fraction of soil
      is ingested by humans. Here, we evaluated soil adherence to human hands for 13
      agricultural soils from Saskatchewan, Canada and 17 different soils from a
      brownfield located in Iqaluit, Nunavut, Canada. In addition, we estimated average
      particle size adhering to human hands for residents of a northern urban setting.
      Further, we estimated how metal concentrations differed between the adhered and
      bulk (< 4 mm) fraction of soil. The average particle size for adhered
      agricultural soils was 34 microm, adhered brownfield soils was 105 microm, and
      particles adhered to human residentswas 36 microm. Metals were significantly
      enriched in these adhered fractions with an average enrichment [(adhered
      bulk)/bulk] in metal concentration of 184% (113% median) for 24 different
      elements. Enrichment was greater for key toxicological elements of concern such
      as chromium (140%), copper (140%), nickel (130%), lead (110%), and zinc (130%)
      and was highest for silver (810%), mercury (630%), selenium (500%), and arsenic
      (420%). Enrichment were positively correlated with carbonate complexation
      constants (but not bulk solubility products) and suggests that the dominant
      mechanism controlling metal enrichment in these samples is a precipitation of
      carbonate surfaces that subsequently adsorb metals. Our results suggest that
      metals of toxicological concern are selectively enriched in the fraction of soil
      that humans incidentally ingest. Investigators should likely process soil samples
      through a 45 microm sieve before estimating the risk associated with contaminated
      soils to humans. The chemical mechanisms resulting in metal enrichment likely
      differ between sites but at our site were linked to surface complexation with
      carbonates.

PMID- 19746742
TI  - Transactivation potencies of Baikal seal constitutive active/androstane receptor
      by persistent organic pollutants and brominated flame retardants.
AB  - To characterize ligand-dependent transcriptional activation of constitutive
      active/androstane receptor (CAR) in aquatic mammals, transactivation potentials
      of the Baikal seal (Pusa sibirica) CAR (bsCAR) by environmental pollutants,
      including persistent organic pollutants (POPs) and brominated flame retardants
      (BFRs), were investigated using an in vitro reporter gene assay, and compared
      with those of the mouse CAR (mCAR). Measurement of luciferase reporter gene
      activities demonstrated that the seal CAR was activated by POPs, including a
      technical mixture of PCBs (Kanechlor-500), certain individual PCB congeners, DDT
      compounds, and trans-nonachlor. No or slight bsCAR-dependent activity was
      detected in experiments with PBDE congeners and HBCDs. The interspecies
      comparison of lowest observed effect concentration (LOEC) for CAR transactivation
      byeach compound revealed that bsCAR responds more sensitively to PCBs than mCAR.
      In addition, bsCAR was weakly deactivated by PBDE99, whereas mCAR transcriptional
      activity decreased weakly by PBDE100, PBDE154, and PBDE187. Comparison of
      reporter gene activities by the congeners with the same IUPAC numbers among PCBs
      and PBDEs revealed that both bsCAR and mCAR were not activated by PBDE99 and
      PBDE153, but were activated by PCB99 and PCB153. The small ligand-binding pocket
      in CAR may contribute to difference in response between PCBs and PBDEs. Given
      that ethical rationale prevents dosing studies with such organohalogens in
      aquatic mammals, our in vitro assay system constructed with CAR cDNA from a
      species of interest provides a useful and realistic alternative approach in
      ecotoxicology.

PMID- 19746743
TI  - Life cycle inventory energy consumption and emissions for biodiesel versus
      petroleum diesel fueled construction vehicles.
AB  - Substitution of soy-based biodiesel fuels for petroleum diesel will alter life
      cycle emissions for construction vehicles. A life cycle inventory was used to
      estimate fuel cycle energy consumption and emissions of selected pollutants and
      greenhouse gases. Real-world measurements using a portable emission measurement
      system (PEMS) were made forfive backhoes, four front-end loaders, and six motor
      graders on both fuels from which fuel consumption and tailpipe emission factors
      of CO, HC, NO(x), and PM were estimated. Life cycle fossil energy reductions are
      estimated it 9% for B20 and 42% for B100 versus petroleum diesel based on the
      current national energy mix. Fuel cycle emissions will contribute a larger share
      of total life cycle emissions as new engines enter the in-use fleet. The average
      differences in life cycle emissions for B20 versus diesel are: 3.5% higher for
      NO(x); 11.8% lower for PM, 1.6% higher for HC, and 4.1% lower for CO. Local urban
      tailpipe emissions are estimated to be 24% lower for HC, 20% lower for CO, 17%
      lower for PM, and 0.9% lower for NO(x). Thus, there are environmental trade-offs
      such as for rural vs urban areas. The key sources of uncertainty in the B20 LCI
      are vehicle emission factors.

PMID- 19746744
TI  - Comparison of life cycle carbon dioxide emissions and embodied energy in four
      renewable electricity generation technologies in New Zealand.
AB  - In order to make the best choice between renewable energy technologies, it is
      important to be able to compare these technologies on the basis of their
      sustainability, which may include a variety of social, environmental, and
      economic indicators. This study examined the comparative sustainability of four
      renewable electricity technologies in terms of their life cycle CO2 emissions and
      embodied energy, from construction to decommissioning and including maintenance
      (periodic component replacement plus machinery use), using life cycle analysis.
      The models developed were based on case studies of power plants in New Zealand,
      comprising geothermal, large-scale hydroelectric, tidal (a proposed scheme), and
      wind-farm electricity generation. The comparative results showed that tidal power
      generation was associated with 1.8 g of CO2/kWh, wind with 3.0 g of CO2/kWh,
      hydroelectric with 4.6 g of CO2/kWh, and geothermal with 5.6 g of CO2/kWh (not
      including fugitive emissions), and that tidal power generation was associated
      with 42.3 kJ/kWh, wind with 70.2 kJ/kWh, hydroelectric with 55.0 kJ/kWh, and
      geothermal with 94.6 kJ/kWh. Other environmental indicators, as well as social
      and economic indicators, should be applied to gain a complete picture of the
      technologies studied.

PMID- 19746745
TI  - Carbon footprint of nations: a global, trade-linked analysis.
AB  - Processes causing greenhouse gas (GHG) emissions benefit humans by providing
      consumer goods and services. This benefit, and hence the responsibility for
      emissions, varies by purpose or consumption category and is unevenly distributed
      across and within countries. We quantify greenhouse gas emissions associated with
      the final consumption of goods and services for 73 nations and 14 aggregate world
      regions. We analyze the contribution of 8 categories: construction, shelter,
      food, clothing, mobility, manufactured products, services, and trade. National
      average per capita footprints vary from 1 tCO2e/y in African countries to
      approximately 30/y in Luxembourg and the United States. The expenditure
      elasticity is 0.57. The cross-national expenditure elasticity for just CO2, 0.81,
      corresponds remarkably well to the cross-sectional elasticities found within
      nations, suggesting a global relationship between expenditure and emissions that
      holds across several orders of magnitude difference. On the global level, 72% of
      greenhouse gas emissions are related to household consumption, 10% to government
      consumption, and 18% to investments. Food accounts for 20% of GHG emissions,
      operation and maintenance of residences is 19%, and mobility is 17%. Food and
      services are more important in developing countries, while mobility and
      manufactured goods rise fast with income and dominate in rich countries. The
      importance of public services and manufactured goods has not yet been
      sufficiently appreciated in policy. Policy priorities hence depend on development
      status and country-level characteristics.

PMID- 19746746
TI  - Indicators on economic risk from global climate change.
AB  - Climate change mitigation requires a rapid decrease of global emissions of
      greenhouse gases (GHGs) from their present value of 8.4 Gt/C/year to, as of
      current knowledge, approximately 1 GtC/year by the end of the century. The
      necessary decrease of GHG emissions will have large impacts on existing and new
      investments with long lifetimes, such coal-fired power plants or buildings.
      Strategic decision making for major investments can be facilitated by indicators
      that express the likelihood of costly retrofitting or shut-down of carbon
      intensive equipment over time. We provide a set of simple indicators that support
      assessment and decision making in this field. Given a certain emissions target,
      carbon allowance prices in a cap-and-trade plan will depend on the development of
      the global economy and the degree to which the target is approached on the global
      and national levels. The indicators measure the degree to which a given emissions
      target is approached nationally and assess risks for long-lived investments
      subject to a range of emissions targets. A comparative case study on existing
      coal-fired power plants with planned plants and utility-scale photovoltaic power
      plants confirms that high risk for coal-fired power plants is emerging. New
      legislation further confirms this result.

PMID- 19746747
TI  - Carbon dioxide postcombustion capture: a novel screening study of the carbon
      dioxide absorption performance of 76 amines.
AB  - The significant and rapid reduction of greenhouse gas emissions is recognized as
      necessary to mitigate the potential climate effects from global warming. The
      postcombustion capture (PCC) and storage of carbon dioxide (CO2) produced from
      the use of fossil fuels for electricity generation is a key technology needed to
      achieve these reductions. The most mature technology for CO2 capture is
      reversible chemical absorption into an aqueous amine solution. In this study the
      results from measurements of the CO2 absorption capacity of aqueous amine
      solutions for 76 different amines are presented. Measurements were made using
      both a novel isothermal gravimetric analysis (IGA) method and a traditional
      absorption apparatus. Seven amines, consisting of one primary, three secondary,
      and three tertiary amines, were identified as exhibiting outstanding absorption
      capacities. Most have a number of structural features in common including steric
      hindrance and hydroxyl functionality 2 or 3 carbons from the nitrogen. Initial
      CO2 absorption rate data from the IGA measurements was also used to indicate
      relative absorption rates. Most of the outstanding performers in terms of
      capacity also showed initial absorption rates comparable to the industry standard
      monoethanolamine (MEA). This indicates, in terms of both absorption capacity and
      kinetics, that they are promising candidates for further investigation.

PMID- 19746748
TI  - Comment on "Environmental occurrence of the enterococcal surface protein (esp)
      gene is an unreliable indicator of human fecal contamination".

PMID- 19746749
TI  - Chemotherapy alone for glottic carcinoma: a need for higher-level evidence.

PMID- 19746750
TI  - Effectiveness of calcium hydroxylapatite paste in vocal rehabilitation.
AB  - OBJECTIVES: We determined the effectiveness of calcium hydroxylapatite (CaHA)
      paste in vocal rehabilitation. METHODS: We examined a retrospective case series
      of 39 adult patients who underwent CaHA paste injection for vocal fold
      rehabilitation over a 5-year period. The outcomes included the change in the
      Voice Handicap Index (VHI) score; procedure-related complications; and the need
      for follow-up voice procedures. RESULTS: The VHI scores demonstrated overall
      improvement, with a decrease from the preoperative mean of 61.2 +/- 24.0 to a
      postoperative mean of 35.9 +/- 26.3 (p = 0.0001) after a mean follow-up time of
      17.8 +/- 13.6 months. The procedure was more likely to succeed in patients with
      paralysis and/or paresis than in patients with glottic soft tissue defects. After
      injection, the VHI scores worsened in 3 of 7 patients (43%) in the soft tissue
      defect group, compared to only 2 of 28 (7%) in the paralysis and/or paresis group
      (p = 0.04). Four of 7 patients with soft tissue defects (57%) required secondary
      vocal procedures to improve the voice, compared to only 2 of 32 (6%) in the
      paralysis and/or paresis group (p = 0.006). CONCLUSIONS: Injection of CaHA paste
      results in significantly improved vocal scores in the majority of patients. Use
      of the paste was less satisfactory in patients with soft tissue defects because
      of poor retention of the paste in the scarred vocal fold remnant.

PMID- 19746751
TI  - Randomized, placebo-controlled evaluation of chlorobutanol, potassium carbonate,
      and irrigation in cerumen removal.
AB  - OBJECTIVES: We evaluated the efficacy over a short period of time of two
      ceruminolytic products, Otocerum (chlorobutanol, phenol, turpentine essence,
      ethyl alcohol; Reig Jofre Laboratories, Barcelona, Spain) and Taponoto (potassium
      carbonate, ethyl alcohol, glycerol, thymol; Teofarma Iberica SA, Barcelona), in
      adult subjects with complete occlusion of the ear canal due to cerumen. METHODS:
      Ninety subjects with complete occlusion of the ear canal were enrolled in a
      randomized, subject- and observer-blinded, placebo-controlled clinical trial. The
      subjects were randomly assigned to one of three different treatments: Otocerum,
      Taponoto, or sterile saline solution (control group). The test medication was
      instilled into an occluded ear for 15 minutes. After this treatment, the
      subject's ear was irrigated with 50 mL of water. The main outcome was the
      proportion of tympanic membranes completely visualized after treatment. RESULTS:
      One subject among the 90 enrolled did not accept a second ear irrigation and was
      excluded from the study. Neither Otocerum nor Taponoto was superior to saline
      solution. Cerumen occlusion resolved in 21 of 32 subjects treated with Otocerum
      (65.6%), 16 of 29 treated with Taponoto (55.2%), and 12 of 28 treated with saline
      solution (42.9%). CONCLUSIONS: The use of Taponoto or Otocerum did not
      significantly improve the proportion of tympanic membranes that were completely
      visualized compared with saline solution when they were instilled 15 minutes
      before ear irrigation.

PMID- 19746752
TI  - Acute myopericarditis complicating acute tonsillitis: a prospective study.
AB  - OBJECTIVES: We describe a prospective study of 100 consecutive cases of acute
      tonsillitis tested for cardiac involvement. There was 1 clear-cut case of acute
      myopericarditis and 5 more patients with pathological findings suggesting cardiac
      complication. METHODS: During a 6-month period (November 2006 to April 2007), we
      prospectively studied 100 consecutive patients admitted to our department with
      acute tonsillitis for the purpose of detecting acute myopericarditis. We obtained
      for each patient a serial electrocardiogram and echocardiogram, and took blood
      samples. All blood samples were analyzed for the presence of the marker troponin
      1 and for cardiac enzymes. RESULTS: One patient (male) had a definitive diagnosis
      of myopericarditis, and another 5 patients (3 of whom were female) had abnormal
      cardiac findings suggestive of myopericarditis. CONCLUSIONS: Otolaryngologists
      should be aware of the possibility of cardiac involvement in acute tonsillitis
      and perform an adequate workup whenever such a possibility is suspected.

PMID- 19746754
TI  - Acute mastoiditis in children: is computed tomography always necessary?
AB  - OBJECTIVES: Acute mastoiditis (AM) is the most common intratemporal complication
      of acute otitis media in children. In the past decade, reports have indicated a
      rise in the incidence of AM in the pediatric population. A parallel rise in the
      use of computed tomography (CT) imaging has occurred. The rise in the use of CT
      scanning in the pediatric population, entraining with it a rise in pediatric
      brain irradiation, has led us to question the necessity of using CT for pediatric
      patients with AM. METHODS: We reviewed the medical files of pediatric patients
      who had AM in the years 2005 through 2007. RESULTS: Fifty patients were
      identified. The gender distribution was equal, and the ages ranged from 4 months
      to 12 years. Of the 46 patients who were admitted to our institution "de novo,"
      only 2 underwent CT scanning on admission, and 4 other patients had CT performed
      during hospitalization. The majority of patients (92%) with AM did not have a CT
      scan performed and were treated conservatively with no complications.
      CONCLUSIONS: In most pediatric patients, CT does not seem to be indispensable in
      the diagnosis of AM. Conservative therapy and close follow-up seem to suffice for
      most.

PMID- 19746753
TI  - Regenerative effects of basic fibroblast growth factor on extracellular matrix
      production in aged rat vocal folds.
AB  - OBJECTIVES: We investigated acute changes in extracellular matrix (ECM) gene
      expression and histologic changes in the deposition of collagen and hyaluronan
      (hyaluronic acid; HA) after basic fibroblast growth factor (bFGF) treatment of
      the aged rat vocal fold. METHODS: For the polymerase chain reaction (PCR)
      experiments, we divided ten 18-month-old Sprague-Dawley rats into two groups that
      received serial injections of sham (saline solution) or bFGF (2 ng/microL) and
      euthanized them 2 weeks after the initial injection to investigate acute changes
      in ECM gene expression. We treated a separate group of 5 animals unilaterally and
      sacrificed them 4 weeks after the initial injection to investigate histologic
      changes in the deposition of collagen and HA. RESULTS: Real-time PCR revealed
      significantly up-regulated HA synthase (HAS)-2, HAS-3, matrix metalloproteinase
      (MMP)-2, and procollagen type I gene expression in the bFGF treatment group as
      compared to the sham treatment group. Histologic staining revealed significantly
      increased deposition of HA in the bFGF-treated vocal fold as compared to the sham
      treated vocal fold. No differences in ECM collagen levels were observed between
      treatment sides. CONCLUSIONS: Basic fibroblast growth factor induced the up
      regulation of HAS-2, HAS-3, MMP-2, and procollagen type I. Histologically, aged
      vocal folds treated with bFGF revealed increased deposition of HA as compared to
      sham-treated vocal folds.

PMID- 19746755
TI  - Temporalis fascia and cartilage-perichondrium composite shield grafts for
      reconstruction of the tympanic membrane.
AB  - OBJECTIVES: We sought to compare the long-term functional results of tympanic
      membrane reconstruction with temporalis fascia and cartilage shield grafting.
      METHODS: This study includes 113 patients who had tympanoplasty type I tympanic
      membrane reconstruction between 1997 and 2007, 47 with tragal cartilage and 66
      with temporalis fascia. Fourteen patients in the cartilage group and 9 patients
      in the temporalis fascia group also had mastoidectomy. The average follow-up was
      3.2 years. The hearing threshold was calculated as the mean value of the
      thresholds for 500, 1,000, 2,000, and 3,000 Hz. A paired-samples t-test was used
      for comparison of the preoperative and postoperative air and bone conduction
      hearing thresholds and air-bone gaps. RESULTS: Significant recovery was found in
      the postoperative air conduction threshold and air-bone gap in both the
      temporalis fascia and cartilage groups as compared to those before surgery (p <
      0.001). However, the average air and bone conduction thresholds and air-bone gap
      were found to be statistically different after surgery in the cartilage group as
      compared to those in the temporalis fascia group. There was no significant
      difference in hearing parameters before and after surgery in patients with or
      without mastoidectomy in either the cartilage group or the temporalis fascia
      group. CONCLUSIONS: The hearing gain in patients with cartilage shield grafting
      was better than that in those who had temporalis fascia tympanoplasty, although
      experimental analysis shows loss of acoustic energy for thick and large shield
      cartilage grafts.

PMID- 19746756
TI  - Characteristics of experimental recurrent laryngeal nerve surgical injury in
      dogs.
AB  - OBJECTIVES: We characterized various recurrent laryngeal nerve (RLN) injuries in
      dogs. METHODS: Sixteen dogs were classified as having complete injuries
      (transection) or incomplete injuries (ligation, half-section, and crush). The
      characteristics of nerve injuries were evaluated by endoscopic examination,
      laryngeal electromyography (LEMG), and histopathologic examination at 0 to 12
      months after the injury. RESULTS: After the RLN injury, the average muscle fiber
      diameter and the average muscle bundle diameter of the affected muscles were
      decreased, and the average number of muscular cell nuclei per square inch
      increased. Fibrillation potentials were found 1 to 3 months after injury, and
      reinnervation potentials appeared 3 to 6 months after incomplete injury. For
      nerve transection and ligation, there was no reaction with LEMG instantly after
      injury involving vocal fold fixation. Vocal fold motion did not improve in
      members of the complete injury group, whereas all of the vocal folds in the
      members of the nerve ligation subgroup had limited activity in the later period.
      Various forms of vocal fold mobility were observed after injury in the half
      section subgroup. Animals in the crush subgroup had normal EMG signals combined
      with abnormal LEMG signals with lower amplitudes after injury. Vocal fold
      fixation was not observed in this subgroup. CONCLUSIONS: We found the causes of
      nerve injury, in order of decreasing severity, to be transection, ligation, half
      section, and crush.

PMID- 19746757
TI  - Comparison of pediatric voice handicap index scores with perceptual voice
      analysis in patients following airway reconstruction.
AB  - OBJECTIVES: We performed a retrospective review to compare a subjective parental
      proxy-derived voice handicap survey to an observer-derived method of measuring
      voice perturbation in children who have undergone airway reconstruction. The main
      outcome measures were the Pediatric Voice Handicap Index (pVHI) total score and
      the Overall Severity score on the Consensus Auditory-Perceptual Evaluation of
      Voice (CAPE-V). METHODS: The percent Overall Severity CAPE-V score (score divided
      by 100) and the percent pVHI score (score divided by 92) were calculated. A
      Wilcoxon signed rank test was used to compare CAPE-V scores with the pVHI total
      scores. The relationship between the pVHI scores and the CAPE-V scores was
      investigated with a Spearman correlation. Subgroup analysis was performed to
      determine the relationship of surgery type to CAPE-V and pVHI scores. RESULTS:
      Fifty subjects with a history of airway surgery who were evaluated between 2005
      and 2008 were identified. Forty-two of the 50 subjects had complete data for
      review. Their median age was 7.1 years (range, 3.3 to 17.9 years). Their pVHI
      total scores had a median of 30 (range, 1 to 80). Their Overall Severity CAPE-V
      scores had a median of 50.5 (range, 0 to 98). Their median CAPE-V percent was
      higher than their median pVHI percent (50.5% versus 32.6%; p = 0.0003). A weak
      correlation was found between the Overall Severity CAPE-V score and the pVHI
      total score (rho = 0.41; p = 0.0003). There was a trend toward higher Overall
      Severity CAPE-V scores in patients who underwent cricotracheal resection. The
      total number of airway surgeries was significantly correlated with the Overall
      Severity CAPE-V score (rho = 0.6; p <0.0001) but not with the pVHI score.
      CONCLUSIONS: Children who undergo airway reconstruction often have a resulting
      voice disturbance that can affect their lives in multiple dimensions. The results
      of this study revealed a weak-to-fair correlation between the parent-reported
      pVHI total score and expert ratings of voice quality using the CAPE-V. In this
      patient population, both of these tools provided important information regarding
      the relationship of the severity of voice disturbance to its handicapping
      effects.

PMID- 19746758
TI  - Unilateral true vocal fold synkinesis presenting with airway obstruction.
AB  - OBJECTIVES: We present a case series of 10 patients with unilateral true vocal
      fold paralysis who presented with airway obstruction. METHODS: A retrospective
      review of the authors' patients at 2 institutions with unilateral true vocal fold
      motion impairment was carried out over a 10-year period. Of these, 10 patients
      were identified who presented with stridor and dyspnea as a result of synkinesis.
      Six cases were a result of thyroidectomy, 1 case resulted from recurrent
      laryngeal nerve section for spasmodic dysphonia, 1 case occurred after anterior
      cervical diskectomy and fusion, and in 2 cases no cause was identified. RESULTS:
      Three patients underwent tracheotomy. Two patients underwent partial
      arytenoidectomy. Seven patients underwent botulinum toxin injection; 2 were
      treated with breathing therapy, and in 1 case breathing therapy was recommended.
      Seven patients underwent treatment with more than 1 method. CONCLUSIONS:
      Unilateral vocal fold paralysis may present with airway obstruction as a result
      of synkinesis. Treatment should be incremental and starts with breathing therapy
      and botulinum toxin injection. Partial arytenoidectomy or tracheotomy may be
      necessary for refractory cases.

PMID- 19746759
TI  - Microdebrider-assisted supraglottoplasty for laryngomalacia.
AB  - OBJECTIVES: We describe our series in the surgical treatment of laryngomalacia
      using a microdebrider. METHODS: We performed a retrospective review of patients
      who underwent microdebrider-assisted supraglottoplasty for laryngomalacia between
      October 2004 and February 2008. Patients with neurologic conditions and secondary
      airway lesions were excluded. The main outcome measures included complications,
      pain, resolution of stridor, presence of aspiration, and need for revision
      surgery. RESULTS: Twenty-eight patients underwent microdebrider-assisted
      supraglottoplasty. The mean age at diagnosis was 109 days, and the mean age at
      the time of the procedure was 182 days. Nineteen patients (68%) had
      gastroesophageal reflux at diagnosis. The average operative time was 35.7 minutes
      (range, 11 to 65 minutes). No intraoperative complications or device problems
      occurred. Two patients remained intubated after the procedure. One patient
      required a tracheotomy, and 1 patient underwent revision supraglottoplasty. Three
      patients had aspiration that resolved. There was negligible pain from the
      procedure, as all patients immediately resumed a diet. All patients had immediate
      or eventual resolution of stridor. CONCLUSIONS: This is the largest series of
      patients who underwent microdebrider-assisted supraglottoplasty for
      laryngomalacia. This procedure is relatively safe, with minimal pain, and
      effective in patients with laryngomalacia. Microdebrider-assisted
      supraglottoplasty is the method of choice for supraglottoplasty in our
      institution.

PMID- 19746760
TI  - Typing vocal fold vibratory patterns in excised larynx experiments via digital
      kymography.
AB  - OBJECTIVES: Signal typing is central to the understanding of vocal fold vibratory
      patterns. Digital kymography (DKG) allows the direct observation of vocal fold
      vibratory patterns, and therefore, using DKG for vibratory signal typing may
      provide a useful complement to traditional signal typing techniques. METHODS:
      Video data collected from 20 larynges excised from mongrel dogs were observed
      with DKG in order to find examples of type 1 (nearly periodic), type 2
      (subharmonic), and type 3 (aperiodic) vibratory patterns. The time series,
      frequency spectra, and correlation dimensions were calculated for each signal
      type. RESULTS: The type 1 pattern showed a periodic time series of glottal edges
      and a discrete frequency spectrum. The type 2 vibratory pattern displayed a time
      series of alternating high- and low-amplitude waves and a frequency spectrum that
      included a subharmonic (F0/2) frequency component. Regular and symmetric
      vibratory patterns were observed in the type 1 and type 2 patterns. The type 3
      vibratory pattern was characterized by an aperiodic time series of glottal edges,
      a broadband frequency spectrum, and irregular and asymmetric vibratory patterns.
      The correlation dimension estimates increased from type 1 to type 2 to type 3.
      CONCLUSIONS: Imaging with DKG demonstrated an ability to assign a signal type to
      various laryngeal vibrations. Signal typing techniques utilizing direct
      observation of the vocal folds could be useful in determining valid methods for
      the analysis of vocal fold vibrations.

PMID- 19746761
TI  - Effect of exogenous hepatocyte growth factor on vocal fold fibroblasts.
AB  - OBJECTIVES: We have previously demonstrated the therapeutic potential of
      hepatocyte growth factor (HGF) in the treatment of vocal fold scarring, although
      how exogenous HGF affects gene expression of endogenous HGF or extracellular
      matrix components in the vocal fold fibroblasts remains unclear. In this in vitro
      study, we aimed to clarify this aspect in order to better understand the effects
      of HGF on the vocal folds. METHODS: Fibroblasts were obtained from the lamina
      propria of the vocal folds of 5 Sprague-Dawley rats and were cultured with HGF at
      concentrations of 100, 10, 1, and 0 ng/mL. The cells were collected on days 1, 3,
      and 7, and the expression of endogenous HGF, its receptor c-Met, transforming
      growth factor-beta1 (TGF-beta1), procollagen types I and III, and hyaluronic acid
      synthase (HAS)-1 and HAS-2 messenger RNAs (mRNAs) was examined by real-time
      reverse transcription-polymerase chain reaction. RESULTS: The expression of
      endogenous HGF and HAS-1 mRNAs increased significantly when exogenous HGF was
      administered at a concentration of 1 ng/mL. On day 1, the expression of TGF-beta1
      and HAS-2 mRNAs increased significantly in response to 1 ng/mL HGF. CONCLUSIONS:
      Exogenous HGF triggered the up-regulation of endogenous HGF, TGF-beta1, HAS-1,
      and HAS-2 mRNAs in vocal fold fibroblasts.

PMID- 19746762
TI  - Acne: from the cradle to the grave.

PMID- 19746763
TI  - What is your diagnosis? Factitious purpura.

PMID- 19746764
TI  - The use of moisturizers as an integral component of topical therapy for rosacea:
      clinical results based on the Assessment of Skin Characteristics Study.
AB  - Skin care regimens have been recommended in conjunction with topical medications
      for the treatment of rosacea. Specifically, a mild cleanser and a moisturizer can
      help relieve symptoms and maintain skin barrier integrity. The Assessment of Skin
      Characteristics Study, a multicenter open-label study (N=102), compared the use
      of a specified skin care regimen with or without the moisturizer component.
      Participants used a facial cleanser immediately before application of azelaic
      acid (AzA) gel 15% twice daily to both sides of the face and then applied the
      provided moisturizer to the right side of the face only. Scores for severity and
      duration of stinging, burning, tingling, and itching were recorded in the morning
      and evening for 7 days. Cumulative symptom scores (CSSs) decreased on the right
      side of the face with facial moisturizer applied.

PMID- 19746765
TI  - What's eating you? Human botfly (Dermatobia hominis).

PMID- 19746766
TI  - Primary cutaneous nodular amyloidosis: case report and review of the literature.
AB  - Primary cutaneous nodular amyloidosis (PCNA) is a rare form of primary cutaneous
      amyloidosis. It presents as waxy yellow-red nodules that are located
      preferentially on the lower extremities, face, scalp, and genitals. Recognition
      of this condition is of particular importance, as primary systemic amyloidosis
      can have a similar cutaneous presentation. We report a case of PCNA in a 52-year
      old woman with systemic lupus erythematosus (SLE) and Sjogren syndrome (SS). We
      discuss the need to evaluate for systemic disease and provide a concise review of
      the literature focusing on clinical presentation, disease associations, and
      management.

PMID- 19746767
TI  - Disseminated Cryptococcus neoformans: case report and review of the literature.
AB  - Cryptococcus neoformans is a yeastlike encapsulated basidiomycetous fungus that
      is able to cross the blood-brain barrier and cause meningitis in both
      immunocompetent and immunocompromised individuals. Cryptococcus neoformans has
      emerged as a major opportunistic pathogen because of the widespread use of
      immunosuppressive therapy. It causes most cryptococcal infections in humans, and
      disseminated infection can have cutaneous manifestations. We report a rare case
      of disseminated C neoformans in a 52-year-old man who underwent an orthotopic
      liver transplant. We also provide a concise review of the literature on C
      neoformans, including its associations, histology, and treatment.

PMID- 19746768
TI  - Standard management options for rosacea, part 2: options according to subtype.
AB  - The standard management options were developed by a consensus committee and
      review panel of 26 experts to assist in providing optimal patient care based on
      the standard classification and grading systems for rosacea that were developed
      to perform research; analyze results and compare data from different sources; and
      provide a common terminology and reference for the diagnosis, treatment, and
      assessment of results in clinical practice. We discuss the standard management
      options for rosacea in 2 parts: (1) overview and broad spectrum of care, and (2)
      management options according to subtype. The menu of options is considered
      provisional and may be expanded and updated as appropriate. Managing the various
      potential signs and symptoms of rosacea calls for consideration of a broad
      spectrum of care, and a more precise selection of therapeutic options may become
      increasingly possible as the mechanisms of action of therapies are more
      definitively established.

PMID- 19746769
TI  - A North American study of adapalene-benzoyl peroxide combination gel in the
      treatment of acne.
AB  - A fixed-dose combination gel with adapalene 0.1% and benzoyl peroxide (BPO) 2.5%
      recently has been developed for the treatment of acne vulgaris. In this
      multicenter, randomized, double-blind, parallel-group, active- and vehicle
      controlled study conducted at 60 centers in the United States, Puerto Rico, and
      Canada, we assessed the efficacy and safety of adapalene-BPO combination gel in
      comparison with adapalene and BPO monotherapies as well as the gel vehicle.
      Participants with moderate facial acne vulgaris (rated 3 on the 5-point
      investigator global assessment of acne severity scale) were recruited and
      randomized to receive once-daily treatment with adapalene-BPO combination gel,
      adapalene monotherapy, BPO monotherapy, or gel vehicle for 12 weeks. They were
      assessed for success rate (the percentage of participants with investigator
      global assessment of acne severity rated clear or almost clear) and percentage
      change in inflammatory lesion (IL), noninflammatory lesion (NIL), and total
      lesion counts. Of the 1668 participants enrolled, 1429 (85.7%) completed the
      study. At study end point, adapalene-BPO combination gel showed a significantly
      higher success rate (P < or = .006) and a greater percentage reduction in all
      acne lesion counts (P < or = .017) compared with the other treatment groups. A
      significant early treatment effect of adapalene-BPO combination gel at week 1
      compared with adapalene monotherapy and vehicle also was observed for all lesion
      count reductions (P<.001). The safety of adapalene-BPO combination gel was
      comparable with adapalene and BPO monotherapies and vehicle. In a large clinical
      trial, the adapalene-BPO fixed-dose combination gel has shown superiority in
      efficacy compared with adapalene and BPO monotherapies and vehicle, with an early
      onset of efficacy and a good safety profile.

PMID- 19746770
TI  - Point/Counterpoint. The linear-quadratic model is inappropriate to model high
      dose per fraction effects in radiosurgery.

PMID- 19746771
TI  - Computer-aided detection of pulmonary embolism in computed tomographic pulmonary
      angiography (CTPA): performance evaluation with independent data sets.
AB  - The authors are developing a computer-aided detection system for pulmonary emboli
      (PE) in computed tomographic pulmonary angiography (CTPA) scans. The pulmonary
      vessel tree is extracted using a 3D expectation-maximization segmentation method
      based on the analysis of eigen-values of Hessian matrices at multiple scales. A
      parallel multiprescreening method is applied to the segmented vessels to identify
      volume of interests (VOIs) that contained suspicious PE. A linear discriminant
      analysis (LDA) classifier with feature selection is designed to reduce false
      positives (FPs). Features that characterize the contrast, gray level, and size of
      PE are extracted as input predictor variables to the LDA classifier. With the IRB
      approval, 59 CTPA PE cases were collected retrospectively from the patient files
      (UM cases). With access permission, 69 CTPA PE cases were randomly selected from
      the data set of the prospective investigation of pulmonary embolism diagnosis
      (PIOPED) II clinical trial. Extensive lung parenchymal or pleural diseases were
      present in 22/59 UM and 26/69 PIOPED cases. Experienced thoracic radiologists
      manually marked 595 and 800 PE as the reference standards in the UM and PIOPED
      data sets, respectively. PE occlusion of arteries ranged from 5% to 100%, with PE
      located from the main pulmonary artery to the subsegmental artery levels. Of the
      595 PE identified in the UM cases, 245 and 350 PE were located in the
      subsegmental arteries and the more proximal arteries, respectively. The detection
      performance was assessed by free response ROC (FROC) analysis. The FROC analysis
      indicated that the PE detection system could achieve an overall sensitivity of
      80% at 18.9 FPs/case for the PIOPED cases when the LDA classifier was trained
      with the UM cases. The test sensitivity with the UM cases was 80% at 22.6
      FPs/cases when the LDA classifier was trained with the PIOPED cases. The
      detection performance depended on the arterial level where the PE was located and
      on the percentage of occlusion. The sensitivity was lower for PE in the
      subsegmental arteries than in more proximal arteries and was lower for PE with
      less than 20% occlusion. The results indicate that the PE detection system
      achieves high sensitivity for PE detection on independent CTPA scans for both the
      PIOPED and UM data sets and demonstrate the potential that the automated PE
      detection approach can be generalized to unknown cases.

PMID- 19746772
TI  - Validation of the final aperture superposition technique to calculate electron
      output factors and depth dose curves.
AB  - The final aperture superposition technique (FAST) is a method to reproduce
      rapidly the electron-beam depth dose curves and output factors that would be
      calculated by a full Monte Carlo simulation. FAST uses precalculated Monte Carlo
      based differential dose arrays and performs a superposition of open and shielded
      contributions to account for arbitrarily shaped insert openings. The objective of
      this work was to refine and validate the accuracy of the FAST method for a full
      range of treatment parameters. Compared to full simulations, raw FAST
      calculations tended to underestimate dose near the surface deposited by particles
      that crossed the shield-opening interface of the insert. In this study, a set of
      empirical correction curves was derived to reduce the errors from this
      "collimator effect." FAST and full simulation calculations were compared for
      every combination of six beam energies (6-21 MeV), four applicator sizes (10-25
      cm), and two source-to-surface distances (SSDs) (100 and 110 cm). Validation
      tests were performed for a total of 192 fields using four sample insert openings:
      an open insert and 2, 3, and 5 cm diameter circular openings. Calculations were
      also performed for four patient inserts with irregularly shaped openings. Using
      the empirical correction curves, systematic errors were reduced, resulting in
      mean dose differences of less than 1% of the maximum full simulation dose. FAST
      relative output factors reproduced full simulation output factors to within 3%
      for all configurations except for the 2 and 3 cm diameter openings for the 6 and
      9 MeV beams at 110 cm SSD. The maximum shift between the FAST and full simulation
      depth dose curves in the 90%-80% fall-off region was less than 3 mm for 97% of
      the fields. For the patient insert calculations, differences in output factors
      and mean differences in depth dose curves were within 1.5% with maximum shifts of
      1.5 mm in the 90%-80% fall-off region. A small set measurements also demonstrated
      3% accuracy in FAST output factors except for a 5% deviation for a 2 cm diameter
      insert for the 6 MeV beam at 110 cm SSD. These results demonstrate that FAST can
      be used to provide output factors and depth dose curves for most clinical cases.

PMID- 19746773
TI  - Imaging of implant needles for real-time HDR-brachytherapy prostate treatment
      using biplane ultrasound transducers.
AB  - Ultrasound imaging is becoming increasingly important in prostate brachytherapy.
      In high-dose-rate (HDR) real-time planning procedures the definition of the
      implant needles is often performed by transrectal ultrasound. This article
      describes absolute measurements of the visibility and accuracy of manual
      detection of implant needle tips and compares measurement results of different
      biplane ultrasound systems in transversal and longitudinal (i.e., sagittal)
      ultrasound modes. To obtain a fixed coordinate system and stable conditions the
      measurements were carried out in a water tank using a dedicated marker system.
      Needles were manually placed in the phantom until the observer decided by the
      real-time ultrasound image that the zero position was reached. A comparison of
      three different ultrasound systems yielded an offset between 0.8 and 3.1 mm for
      manual detection of the needle tip in ultrasound images by one observer. The
      direction of the offset was discovered to be in the proximal direction, i.e., the
      actual needle position was located more distally compared to the ultrasound-based
      definition. In the second part of the study, the ultrasound anisotropy of trocar
      implant needles is reported. It was shown that the integrated optical density in
      a region of interest around the needle tip changes with needle rotation. Three
      peaks were observed with a phase angle of 120 degrees. Peaks appear not only in
      transversal but also in longitudinal ultrasound images, with a phase shift of 60
      degrees. The third section of this study shows results of observer dependent
      influences on needle tip detection in sagittal ultrasound images considering
      needle rotation. These experiments were carried out using the marker system in a
      water tank. The needle tip was placed exactly at the position z=0 mm. It was
      found that different users tend to differently interpret the same ultrasound
      images. The needle tip was manually detected five times in the ultrasound images
      by three experienced observers at positions (+/- standard deviation) -0.53 +/-
      0.16, -0.16 +/- 0.14, and -0.30 +/- 0.16 mm using a gain of 15 dB. The minus sign
      indicates that the needle tips were detected more proximally than the actual
      position of the needle tip. When using a gain of -15 dB the mean values of two
      observers resulted in -0.62 +/- 0.08 and -0.51 +/- 0.12 mm. Additionally an
      alternative approach to the direct needle tip definition was investigated. Two
      observers detected the solid part of the needle tip in sagittal images. This
      solid part, often named as "dead space end," is the distance between the needle
      tip and the beginning of the hollow part of the implant needle. The dead space
      end is 6.2 mm for the investigated needle type. Two users found mean values of 
      6.70 +/- 0.16 and -7.00 +/- 0.06 mm, respectively, for 15 dB gain and -6.90 +/-
      0.09 and -7.02 +/- 0.06 mm using the -15 dB gain setting. The results show that
      ultrasound-based needle tip definition in sagittal viewing mode is accurate. The
      inter- and intraobserver errors should, however, be taken into account. A lower
      gain setting of the ultrasound system reduces the intraobserver error.

PMID- 19746774
TI  - Tracking brain motion during the cardiac cycle using spiral cine-DENSE MRI.
AB  - Cardiac-synchronized brain motion is well documented, but the accurate
      measurement of such motion on the pixel-by-pixel basis has been hampered by the
      lack of proper imaging technique. In this article, the authors present the
      implementation of an autotracking spiral cine displacement-encoded stimulation
      echo (DENSE) magnetic resonance imaging (MRI) technique for the measurement of
      pulsatile brain motion during the cardiac cycle. Displacement-encoded dynamic MR
      images of three healthy volunteers were acquired throughout the cardiac cycle
      using the spiral cine-DENSE pulse sequence gated to the R wave of an
      electrocardiogram. Pixelwise Lagrangian displacement maps were computed, and 2D
      displacement as a function of time was determined for selected regions of
      interests. Different intracranial structures exhibited characteristic motion
      amplitude, direction, and pattern throughout the cardiac cycle. Time-resolved
      displacement curves revealed the pathway of pulsatile motion from brain stem to
      peripheral brain lobes. These preliminary results demonstrated that the spiral
      cine-DENSE MRI technique can be used to measure cardiac-synchronized pulsatile
      brain motion on the pixel-by-pixel basis with high temporal/spatial resolution
      and sensitivity.

PMID- 19746775
TI  - Stochastic rank correlation: a robust merit function for 2D/3D registration of
      image data obtained at different energies.
AB  - In this article, the authors evaluate a merit function for 2D/3D registration
      called stochastic rank correlation (SRC). SRC is characterized by the fact that
      differences in image intensity do not influence the registration result; it
      therefore combines the numerical advantages of cross correlation (CC)-type merit
      functions with the flexibility of mutual-information-type merit functions. The
      basic idea is that registration is achieved on a random subset of the image,
      which allows for an efficient computation of Spearman's rank correlation
      coefficient. This measure is, by nature, invariant to monotonic intensity
      transforms in the images under comparison, which renders it an ideal solution for
      intramodal images acquired at different energy levels as encountered in
      intrafractional kV imaging in image-guided radiotherapy. Initial evaluation was
      undertaken using a 2D/3D registration reference image dataset of a cadaver spine.
      Even with no radiometric calibration, SRC shows a significant improvement in
      robustness and stability compared to CC. Pattern intensity, another merit
      function that was evaluated for comparison, gave rather poor results due to its
      limited convergence range. The time required for SRC with 5% image content
      compares well to the other merit functions; increasing the image content does not
      significantly influence the algorithm accuracy. The authors conclude that SRC is
      a promising measure for 2D/3D registration in IGRT and image-guided therapy in
      general.

PMID- 19746776
TI  - In vivo detection and imaging of low-density foreign body with microwave-induced
      thermoacoustic tomography.
AB  - Radiography or computed tomography is the most widely available imaging tool for
      foreign body detection. However, the detectability of low-density substances by x
      ray is very poor when located in soft tissues. Various dielectric loss factors of
      foreign bodies contribute great microwave absorption heterogeneity compared with
      the surrounding tissue. A fast thermoacoustic tomography system at 1.2 and 6 GHz
      was developed to detect foreign targets in small animals. The 6 GHz system had a
      much higher signal-to-noise ratio in near-surface imaging but smaller imaging
      depth than the 1.2 GHz system. The effects of microwave distribution
      inhomogeneity on nonuniform excitation of acoustic pressure were studied and a
      corresponding calibration algorithm for image distortion was provided and
      experimentally examined. Thermoacoustic images of radiolucent objects including
      glass fiber, wood, and bamboo hidden in phantom and residual in living mice were
      compared with radiography and ultrasonography. Good contrast was obtained between
      the foreign bodies and the tissue surrounding it, and the location and size of
      the lesion targets in thermoacoustic images were in good agreement with the
      actual sample. The experimental results demonstrate that thermoacoustic
      tomography may become the ideal modality for radiolucent foreign body detection
      and imaging in animals and human.

PMID- 19746777
TI  - Verification of four-dimensional photon dose calculations.
AB  - Recent work in the area of thoracic treatment planning has been focused on trying
      to explicitly incorporate patient-specific organ motion in the calculation of
      dose. Four-dimensional (4D) dose calculation algorithms have been developed and
      incorporated in a research version of a commercial treatment planning system
      (Pinnacle3, Philips Medical Systems, Milpitas, CA). Before these 4D dose
      calculations can be used clinically, it is necessary to verify their accuracy
      with measurements. The primary purpose of this study therefore was to evaluate
      and validate the accuracy of a 4D dose calculation algorithm with phantom
      measurements. A secondary objective was to determine whether the performance of
      the 4D dose calculation algorithm varied between different motion patterns and
      treatment plans. Measurements were made using two phantoms: A rigid moving
      phantom and a deformable phantom. The rigid moving phantom consisted of an
      anthropomorphic thoracic phantom that rested on a programmable motion platform.
      The deformable phantom used the same anthropomorphic thoracic phantom with a
      deformable insert for one of the lungs. Two motion patterns were investigated for
      each phantom: A sinusoidal motion pattern and an irregular motion pattern
      extracted from a patient breathing profile. A single-beam plan, a multiple-beam
      plan, and an intensity-modulated radiation therapy plan were created. Doses were
      calculated in the treatment planning system using the 4D dose calculation
      algorithm. Then each plan was delivered to the phantoms and delivered doses were
      measured using thermoluminescent dosimeters (TLDs) and film. The measured doses
      were compared to the 4D-calculated doses using a measured-to-calculated TLD ratio
      and a gamma analysis. A relevant passing criteria (3% for the TLD and 5% /3 mm
      for the gamma metric) was applied to determine if the 4D dose calculations were
      accurate to within clinical standards. All the TLD measurements in both phantoms
      satisfied the passing criteria. Furthermore, 42 of the 48 evaluated films
      fulfilled the passing criteria. All films that did not pass the criteria were
      from the rigid phantom moving with irregular motion. The author concluded that if
      patient breathing is reproducible, the 4D dose calculations are accurate to
      within clinically acceptable standards. Furthermore, they found no statistically
      significant differences in the performance of the 4D dose calculation algorithm
      between treatment plans.

PMID- 19746778
TI  - Determination of exact reconstruction regions in composite-circling cone-beam
      tomography.
AB  - Image reconstruction of a short portion of a long object using longitudinally
      truncated cone-beam data is important for major medical computed tomography (CT)
      applications, especially cardiac CT. Cardiac CT is an essential imaging tool for
      the diagnosis and therapeutic assessment of heart defects, cardiovascular
      diseases, and lung diseases, but it is still limited by suboptimal image quality.
      Recently, saddle-curve and composite-circling scanning modes have been proposed
      to solve this problem using exact reconstruction formulas. However, saddle-curve
      scanning involves both circular and linear motions, while composite-circling
      scanning conveniently involves just circular motions. Because saddle-curve
      scanning is difficult to implement mechanically, composite-circling scanning
      provides another, hopefully easier, approach: An x-ray focal spot in an x-ray
      tube is rotated on a plane facing the heart, while the x-ray tube and possibly
      the detector are simultaneously rotated on the gantry plane. This article
      determines regions for chord-based exact reconstruction in the composite-circling
      scanning mode and compares them to those in the saddle-curve scanning mode. For
      different scanning parameter combinations, this article finds the largest sphere
      centered at the origin that can be embedded inside the exact reconstruction
      region. This article also shows that the embedded spheres become larger when the
      x-ray focal spot rotates at variable speeds, allowing the scanning curve to cover
      a larger object. In summary, this article derives guidelines for prototyping a
      new cardiac CT scanner to meet the goals of reducing radiation dose and
      increasing spatial and temporal resolution.

PMID- 19746779
TI  - Sensitivity of fluorophore-quencher labeled microbubbles to externally applied
      static pressure.
AB  - A fluorophore-quencher (F-Q) labeled microbubble system is proposed as a sensor
      for measuring externally applied static pressure distribution in a tumor. To
      quantify the sensitivity of such an F-Q bubble system to the externally applied
      pressure, a model describing bubble response to the static pressure was derived.
      Additionally, a model connecting the fluorescence lifetime and bubble radius was
      developed for the basic F-Q bubble system. The sensitivity is quantified based on
      these models given typical parameters. Results show that it is possible to
      resolve as low as 1 mm Hg pressure variation when both the F-Q bubble system and
      the measurement system are optimized. Strategies for optimizing an F-Q bubble
      system are discussed.

PMID- 19746780
TI  - Efficient implementations of a pseudodynamical stochastic filtering strategy for
      static elastography.
AB  - A computationally efficient pseudodynamical filtering setup is established for
      elasticity imaging (i.e., reconstruction of shear modulus distribution) in soft
      tissue organs given statically recorded and partially measured displacement data.
      Unlike a regularized quasi-Newton method (QNM) that needs inversion of ill
      conditioned matrices, the authors explore pseudodynamic extended and ensemble
      Kalman filters (PD-EKF and PD-EnKF) that use a parsimonious representation of
      states and bypass explicit regularization by recursion over pseudotime. Numerical
      experiments with QNM and the two filters suggest that the PD-EnKF is the most
      robust performer as it exhibits no sensitivity to process noise covariance and
      yields good reconstruction even with small ensemble sizes.

PMID- 19746781
TI  - Quality assurance for clinical implementation of an electromagnetic tracking
      system.
AB  - The Calypso Medical 4D localization system utilizes alternating current
      electromagnetics for accurate, real-time tumor tracking. A quality assurance
      program to clinically implement this system is described here. Testing of the
      continuous electromagnetic tracking system (Calypso Medical Technologies,
      Seattle, WA) was performed using an in-house developed four-dimensional stage and
      a quality assurance fixture containing three radiofrequency transponders at
      independently measured locations. The following tests were performed to validate
      the Calypso system: (a) Localization and tracking accuracy, (b) system
      reproducibility, (c) measurement of the latency of the tracking system, and (d)
      measurement of transmission through the Calypso table overlay and the
      electromagnetic array. The translational and rotational localization accuracies
      were found to be within 0.01 cm and 1.0 degree, respectively. The reproducibility
      was within 0.1 cm. The average system latency was measured to be within 303 ms.
      The attenuation by the Calypso overlay was measured to be 1.0% for both 6 and 18
      MV photons. The attenuations by the Calypso array were measured to be 2% and 1.5%
      for 6 and 18 MV photons, respectively. For oblique angles, the transmission was
      measured to be 3% for 6 MV, while it was 2% for 18 MV photons. A quality
      assurance process has been developed for the clinical implementation of an
      electromagnetic tracking system in radiation therapy.

PMID- 19746782
TI  - How does the injection protocol influence the attenuation-time curve in CT
      perfusion measurements: comparison of measured and simulated data.
AB  - In this study the authors compared a computer simulation that models bolus
      dispersion during the first pass to patient PCT data acquired with three
      different types of injection protocols. PCT was performed in 27 patients with one
      of the three injection protocols: (1) Monophasic bolus injection with saline
      flush, (2) monophasic bolus injection without saline flush, and (3) biphasic
      bolus injection with saline flush. They performed computer simulation to model
      bolus dispersion in the three injection protocols. Finally, they compared the
      simulated attenuation-time curves to the measured ones. The simulated attenuation
      time curves corresponded well to the measured data for protocol 1. With protocol
      2 they found that simulation predicts bolus kinetics correctly but overestimates
      the concentration by about 31%. They attributed this to the missing saline flush.
      By comparing the simulated and measured data, they could show that without saline
      flush about 1/3 of the contrast agent does not contribute to the first pass. For
      the biphasic injection (protocol 3), they found that the first part of the
      attenuation-time curve can be modeled by simulating the bolus dispersion of only
      the high-flow portion of the injected bolus. Although the simulation model does
      only take into account of the first pass of the bolus, it is a useful tool to
      analyze and predict effects of modified injection protocols.

PMID- 19746783
TI  - Ultrasonic focusing through the ribs using the DORT method.
AB  - Thermal ablation induced by high intensity focused ultrasound has produced
      promising clinical results to treat hepatocarcinoma and other liver tumors.
      However skin burns have been reported due to the high absorption of ultrasonic
      energy by the ribs. This study proposes a method to produce an acoustic field
      focusing on a chosen target while sparing the ribs using the decomposition of the
      time-reversal operator (DORT method). The idea is to apply an excitation weight
      vector to the transducers array which is orthogonal to the subspace of emissions
      focusing on the ribs. A linear array of transducers has been used to measure the
      set of singular vectors associated with a chest phantom, made of three human ribs
      immersed in water, and to produce the desired acoustic fields. The resulting
      propagating fields have been measured both in the focal plane and in the plane of
      the ribs using a needle hydrophone. The ratio of the energies absorbed at the
      focal point and on the ribs has been enhanced up to 100-fold, as demonstrated by
      the measured specific absorption rates.

PMID- 19746784
TI  - A feasibility study of novel ultrasonic tissue characterization for prostate
      cancer diagnosis: 2D spectrum analysis of in vivo data with histology as gold
      standard.
AB  - This study demonstrates the feasibility of using a novel 2D spectrum ultrasonic
      tissue characterization (UTC) technique for prostate-cancer diagnosis. Normalized
      2D spectra are computed by performing Fourier transforms along the range (beam)
      and the cross-range directions of the digital radio-frequency echo data, then
      dividing by a reference spectrum. This 2D spectrum method provides axial and
      lateral information of tissue microstructures, an improvement over the current 1D
      spectrum analysis which only provides axial information. A pilot study was
      conducted on four prostate-cancer patients who underwent radical prostatectomies.
      Cancerous and noncancerous regions of interest, identified through histology,
      were compared using four 2D spectral parameters: peak value and 3 dB width of the
      radially integrated spectral power (RISP), slope and intercept of the angularly
      integrated spectral power (AISP). For noncancerous and cancerous prostatic
      tissues, respectively, our investigation yielded 23 +/- 1 and 26 +/- 1 dB for
      peak value of RISP, 7.8 +/- 0.5 degrees and 7.6 +/- 0.6 degrees for 3 dB of RISP,
      -2.1 +/- 0.2 and -2.7 +/- 0.4 dB/MHz for slope of AISP, and 92 +/- 5 and 112 +/-
      6 dB for intercept of AISP. Preliminary results indicated that 2D spectral UTC
      has the potential for identifying tumor-bearing regions within the prostate
      gland.

PMID- 19746785
TI  - Cone-beam CT dosimetry for the positional variation in isocenter: a Monte Carlo
      study.
AB  - This study investigated variations in kilovoltage cone-beam computed tomography
      (kV-CBCT) dosimetry for a change in the isocenter positions in the head-and-neck,
      lung-breast, and pelvis Rando phantoms using Monte Carlo simulations. Phase space
      kV-CBCT beams with energy of 120 kVp for the XVI system equipped to the Elekta
      Synergy medical linear accelerator were used to calculate dose distributions for
      the head-and-neck, lung-breast, and pelvis phantoms, with isocenters in the
      original positions near to the center of each phantom using the EGSnrc-based
      Monte Carlo code. Dose calculations were repeated with kV-CBCT isocenters shifted
      from the original positions along the x, y, and z axes. The relative dose ratio
      profiles, corresponding to different isocenter positions normalized to the
      original ones, were compared to evaluate the variations in the dose distribution
      due to isocentric shifts. Moreover, the relative dose at the isocenter, maximum
      dose, and mean dose for each isocenteric shift in the three phantoms were
      calculated. In this study, the original isocenter/center of the phantom was used
      as the reference for dose normalization. When the isocenter was chosen off from
      the center of the head-and-neck phantom, the maximum and mean imaging doses were
      found, varying by 14% and 15% in the anterior-posterior directions and 9% and 7%
      in the left-right directions. These dosimetric variations were slightly larger
      (17% and 17% in the anterior-posterior directions and 19% and 16% in the left
      right directions) for the lung-breast phantom. For the pelvis phantom, the
      maximum and mean imaging doses varied by 10% and 22% in the anterior-posterior
      directions and 9% and 14% in the left-right directions with changes in the
      isocenter positions. Since the typical imaging dose is in the range of 2-8 cGy
      for the soft tissue per kV-CBCT acquisition, the variation in the imaging dose
      due to the patient setup error (approximately 2 cm) is insignificant compared to
      the original designed imaging dose. Moreover, the information on imaging dose
      varying as a function of the choices of isocenter or imaging center is useful for
      the physician and planner when they design the treatment plan for image-guided
      radiotherapy.

PMID- 19746786
TI  - Volumetric HIFU ablation under 3D guidance of rapid MRI thermometry.
AB  - A volumetric sonication method is proposed that produces volume ablations by
      steering the focal point along a predetermined trajectory consisting of multiple
      concentric outward-moving circles. This method was tested in vivo on pig thigh
      muscle (32 ablations in nine animals). Trajectory diameters were 4, 12, and 16 mm
      with sonication duration depending on the trajectory size and ranging from 20 to
      73 s. Despite the larger trajectories requiring more energy to reach necrosis
      within the desired volume, the ablated volume per unit applied energy increased
      with trajectory size, indicating improved treatment efficiency for larger
      trajectories. The higher amounts of energy required for the larger trajectories
      also increased the risk of off-focus heating, especially along the beam axis in
      the near field. To avoid related adverse effects, rapid volumetric multiplane MR
      thermometry was introduced for simultaneous monitoring of the temperature and
      thermal dose evolution along the beam axis and in the near field, as well as in
      the target region with a total coverage of six slices acquired every 3 s. An
      excellent correlation was observed between the thermal dose and both the
      nonperfused (R=0.929 for the diameter and R=0.964 for the length) and oedematous
      (R=0.913 for the diameter and R=0.939 for the length) volumes as seen in contrast
      enhanced T1-weighted difference images and T2-weighted postsonication images,
      respectively. Histology confirmed the presence of a homogeneous necrosis inside
      the heated volumes. These results show that volumetric high-intensity focused
      ultrasound (HIFU) sonication allows for efficiently creating large thermal
      lesions while reducing treatment duration and also that the rapid multiplane MR
      thermometry improves the safety of the therapeutic procedure by monitoring
      temperature evolution both inside as well as outside the targeted volume.

PMID- 19746787
TI  - Effect of edema associated with 131Cs prostate permanent seed implants on
      dosimetric quality indices.
AB  - This study was designed to investigate the effect of prostatic edema on various
      dosimetric quality indices following transperineal permanent 131Cs seed implant.
      Thirty-one patients with early prostate cancer, who received 131Cs permanent seed
      implant, were included in this study. Each patient received a prescribed dose of
      115 Gy from the implant. Transrectal ultrasound (U.S.) was used to measure the
      preimplant prostate volume and pre- and postneedle implant volumes, and
      postimplant CT images were used to obtain postimplant prostate volumes at days 0,
      14, and 28 for all patients. The magnitude of edema was determined by comparing
      the preneedle and postimplant prostate volumes, which was used to compute the
      half life of the edema using the least-squares method. Dose volume histograms
      were generated for each set of volumes to determine the percentage of the
      prostate volume that received a dose equal to or greater than the prescribed dose
      to compute the quality index (V100) and fractional D90 (FD90). There were no
      statistically significant differences between the postneedle and postimplant (day
      0) volumes obtained by U.S. and CT scanned images (student's t-test p=0.56). The
      mean half life of the edema was found to be (9.72 +/- 8.31) days (mean +/- 1 SD),
      ranging from 3.64 to 34.48 days. The mean values of V100 and FD90 from preimplant
      plan to postimplant plan at day 0 were decreased by 8.0% and 6.3%, respectively.
      On the other hand, the mean values of V100 and FD90 increased with increasing
      postimplant time and attained optimal values when postimplant volume reached the
      original volume of the prostate. The short half life 131Cs radioactive source
      delivered about 85% of the prescribed dose before the prostate reached its
      original volume. Therefore, improvement in V100 and FD90 due to edema decay does
      not improve the physical dose delivery to the prostate. It is important to note
      that at the time of 131Cs implant, the effect of edema must be accounted for when
      defining the seed positions. Implants performed based only on the guidance of a
      preimplant volume study would result in poor dosimetric results for 131Cs
      implants.

PMID- 19746788
TI  - The local enhancement of radiation dose from photons of MeV energies obtained by
      introducing materials of high atomic number into the treatment region.
AB  - With the advent of therapeutic radiation treatment machines with photon end point
      energies of several MeV, a new channel is available to transfer the photon energy
      to biological material, namely, pair production. This process has a photon
      threshold energy of 1.02 MeV. The probability of pair production, which depends
      on the square of the atomic number (Z) of the interacting material, increases
      markedly as the photon energy is further increased. As the goal of treatment
      planning in radiation therapy is to locally maximize the absorbed dose in
      abnormal cells and minimize the dose in surrounding normal cells, in this study
      the authors measured the dose enhancement which could be expected if a high-Z
      material such as gold was present adjacent to tumor sites during irradiation. The
      authors used photon beams produced by electron accelerators with energies ranging
      from 6 to 25 MV. They chose either gold or lead foils as high-Z materials, the
      measurements being repeated using the same geometry but replacing the high-Z
      materials with a low-Z material (aluminum). The comparison of the experimental
      results using low- and high-Z materials verified the theoretical prediction of
      the expected dose enhancement. The effect of finite range of the electron
      positron pairs was also studied by varying the spacing between two foils placed
      parallel or orthogonal to the incident photon beam. Using an 18 MV photon beam,
      the authors observed a maximum dose enhancement of 44%. They intend therefore to
      proceed from these phantom studies to animal measurements.

PMID- 19746789
TI  - High resolution entry and exit Monte Carlo dose calculations from a linear
      accelerator 6 MV beam under the influence of transverse magnetic fields.
AB  - A current concern with 6 MV transverse field MRI-linac hybrid systems is the
      predicted increases in skin dose (both the entry and exit sides) caused by the
      effects of the magnetic field on secondary electrons. In this work high
      resolution GEANT4 Monte Carlo simulations have been performed at the beam central
      axis in the entry and exit regions of a water phantom to predict surface (0
      microm depth) and skin (70 microm depth) doses when placed in such a hybrid
      system. A 30 x 30 x 20 cm3 water phantom with 10 microm thick voxels has been
      simulated by being irradiated perpendicularly with a 6 MV photon beam (Varian
      2100C) of sizes of 5 x 5, 10 x 10, 15 x 15, and 20 x 20 cm2. Uniform transverse
      magnetic fields of 0.2, 0.75, 1.5, and 3 T with varying thickness above the
      phantom have been investigated. Simulations with and without lepton contamination
      have been performed. In the entry region the high resolution scoring has yielded
      unexpected surface and skin doses. There is a small amount of nonpurged air
      generated lepton contamination that originates immediately above the phantom
      surface and delivers its dose over very short longitudinal distances in the entry
      region. At 0.2 T the surface and skin doses are not accurately predicted using
      lepton-contamination-free simulations and extrapolated lower resolution scoring.
      Lepton-free simulations are up to 7% of Dmax lower than simulations with leptons.
      However, compared to 0 T, entry skin dose is reduced at 0.2 and 0.75 T but
      increases to 28%-31% of Dmax at 3 T. For skin doses at the central axis in the
      exit region, high resolution scoring shows relative increases of 38%-106%,
      depending on the magnetic field strength and field size. These values are also up
      to 20% higher than lower resolution results. The shape of the exit dose profiles
      varies unpredictably and so extrapolation of low resolution data is insufficient.
      In order to achieve accurate Monte Carlo skin dosimetry in a transverse field MRI
      linac system, the authors recommend using high resolution scoring. In systems of
      0.2 T the inclusion of air-generated lepton contamination is also recommended.

PMID- 19746790
TI  - Scan pattern optimization for uniform proton beam scanning.
AB  - Magnetic beam scanning allows one to spread proton beam over the desired
      radiation field area, improving beam utilization and conformity to the target
      area. This article discusses generic scan forms for generating uniform circular
      and rectangular fields and establishes criteria that can be applied to optimize
      selected scan patterns. During construction of the Midwest Proton Radiotherapy
      Institute (MPRI), Indiana University developed a magnetically scanned beam
      spreading system for the 3 m long gantry nozzle. Based on the commissioning
      experience, criteria for optimizing the scan patterns were derived. A numerical
      integration model was used to perform initial optimization of the resulting dose
      distribution. The selected scan patterns were then experimentally validated via
      test irradiation of Gafchromic films. Generic spiral and linear scan forms are
      proposed capable of delivering uniform circular and rectangular fields in
      continuous scanning mode. The test irradiations performed indicate that dose
      uniformity is within +/- 3% for both scan forms and that penumbra of the
      uncollimated field can approach the radius of the pristine beam spot. A well
      designed uniform scanning system can have a large library of uniform circular and
      rectangular fields of different sizes, which would increase beam utilization and
      minimize out-of-field dose to the patient.

PMID- 19746791
TI  - Gadolinium dose enhancement studies in microbeam radiation therapy.
AB  - Microbeam radiation therapy (MRT) is an innovative technique to treat brain
      tumors. The synchrotron generated x-ray beam, used for the treatment, is
      collimated and delivered in an array of narrow micrometer-sized planar
      rectangular fields. Several preclinical experiments performed at the Brookhaven
      National Laboratory (BNL) and at the European Synchrotron Radiation Facility
      (ESRF) have shown the sparing effect of the healthy tissue and the ablation of
      tumors in several animal models. It has also been determined that MRT yields a
      higher therapeutic index than nonsegmented beams of the same energy. This
      therapeutic index could be greatly improved by loading the tumor with high atomic
      number (Z) contrast agents. In this work, the dose enhancement factors and the
      peak to valley dose ratios (PVDRs) are assessed for different gadolinium (Z = 64)
      concentrations in the tumor and different microbeam energies by using Monte Carlo
      simulations (PENELOPE 2006 code). A significant decrease in the PVDR values in
      the tumor, and therefore a relevant increase in the dose deposition, is found in
      the presence of gadolinium. The optimum energy for the dose deposition in the
      tumor while keeping a high PVDR in the healthy tissues, which guaranties their
      sparing, has been investigated.

PMID- 19746792
TI  - A scheme for multisource interior tomography.
AB  - Currently, x-ray computed tomography (CT) requires source scanning so that
      projections can be collected from various orientations for image reconstruction.
      Limited by the scanning time, the temporal resolution of CT is often inadequate
      when rapid dynamics is involved in an object to be reconstructed. To meet this
      challenge, here the authors propose a scheme of multisource interior tomography
      for ultrafast imaging that reconstructs a relatively small region of interest
      (ROI). Specifically, such a ROI is irradiated in parallel with narrow x-ray beams
      defined by many source-detector pairs for data acquisition. This ROI can be then
      reconstructed using the interior tomography approach. To demonstrate the merits
      of this approach, the authors report interior reconstruction from in vivo lung CT
      data at a much reduced radiation dose, which is roughly proportional to the ROI
      size. The results suggest a scheme for ultrafast tomography (such as with a
      limited number of sources and in a scanning mode) to shorten data acquisition
      time and to suppress motion blurring.

PMID- 19746793
TI  - Monte Carlo-based adaptive EPID dose kernel accounting for different field size
      responses of imagers.
AB  - The aim of this study is to present an efficient method to generate imager
      specific Monte Carlo (MC)-based dose kernels for amorphous silicon-based
      electronic portal image device dose prediction and determine the effective
      backscattering thicknesses for such imagers. EPID field size-dependent responses
      were measured for five matched Varian accelerators from three institutions with 6
      MV beams at the source to detector distance (SDD) of 105 cm. For two imagers,
      measurements were made with and without the imager mounted on the robotic
      supporting arm. Monoenergetic energy deposition kernels with 0-2.5 cm of water
      backscattering thicknesses were simultaneously computed by MC to a high
      precision. For each imager, the backscattering thickness required to match
      measured field size responses was determined. The monoenergetic kernel method was
      validated by comparing measured and predicted field size responses at 150 cm SDD,
      10 x 10 cm2 multileaf collimator (MLC) sliding window fields created with 5, 10,
      20, and 50 mm gaps, and a head-and-neck (H&N) intensity modulated radiation
      therapy (IMRT) patient field. Field size responses for the five different imagers
      deviated by up to 1.3%. When imagers were removed from the robotic arms, response
      deviations were reduced to 0.2%. All imager field size responses were captured by
      using between 1.0 and 1.6 cm backscatter. The predicted field size responses by
      the imager-specific kernels matched measurements for all involved imagers with
      the maximal deviation of 0.34%. The maximal deviation between the predicted and
      measured field size responses at 150 cm SDD is 0.39%. The maximal deviation
      between the predicted and measured MLC sliding window fields is 0.39%. For the
      patient field, gamma analysis yielded that 99.0% of the pixels have gamma < 1 by
      the 2%, 2 mm criteria with a 3% dose threshold. Tunable imager-specific kernels
      can be generated rapidly and accurately in a single MC simulation. The resultant
      kernels are imager position independent and are able to predict fields with
      varied incident energy spectra and a H&N IMRT patient field. The proposed
      adaptive EPID dose kernel method provides the necessary infrastructure to build
      reliable and accurate portal dosimetry systems.

PMID- 19746794
TI  - Nonlinear regression-based method for pseudoenhancement correction in CT
      colonography.
AB  - In CT colonography (CTC), orally administered positive-contrast tagging agents
      are often used for differentiating residual bowel contents from native colonic
      structures. However, tagged materials can sometimes hyperattenuate observed CT
      numbers of their adjacent untagged materials. Such pseudoenhancement complicates
      the differentiation of colonic soft-tissue structures from tagged materials,
      because pseudoenhanced colonic structures may have CT numbers that are similar to
      those of tagged materials. The authors developed a nonlinear regression-based
      (NLRB) method for performing a local image-based pseudoenhancement correction of
      CTC data. To calibrate the correction parameters, the CT data of an
      anthropomorphic reference phantom were correlated with those of partially tagged
      phantoms. The CTC data were registered spatially by use of an adaptive
      multiresolution method, and untagged and tagged partial-volume soft-tissue
      surfaces were correlated by use of a virtual tagging scheme. The NLRB method was
      then optimized to minimize the difference in the CT numbers of soft-tissue
      regions between the untagged and tagged phantom CTC data by use of the Nelder
      Mead downhill simplex method. To validate the method, the CT numbers of untagged
      regions were compared with those of registered pseudoenhanced phantom regions
      before and after the correction. The CT numbers were significantly different
      before performing the correction (p<0.01), whereas, after the correction, the
      difference between the CT numbers was not significant. The effect of the
      correction was also tested on the size measurement of polyps that were covered by
      tagging in phantoms and in clinical cases. In phantom cases, before the
      correction, the diameters of 12 simulated polyps submerged in tagged fluids that
      were measured in a soft-tissue CT display were significantly different from those
      measured in an untagged phantom (p<0.01), whereas after the correction the
      difference was not significant. In clinical cases, before the correction, the
      diameters of 29 colonoscopy-confirmed 3-14 mm polyps affected by tagging that
      were measured in a soft-tissue CT display were significantly different from those
      measured in a lung CT display (p<0.0001) or in colonoscopy (p<0.05), whereas
      after the correction the difference was not significant. Finally, the effect of
      the correction was tested on automated detection of 25 polyps > or =6 mm affected
      by tagging in 56 clinical CTC cases. The application of the correction increased
      the detection accuracy from 60% with 5.0 FP detections per patient without
      correction to 96% with 2.9 FP detections with correction. This improvement in
      detection accuracy was statistically significant (p<0.05). The results indicate
      that the proposed NLRB method can yield an accurate pseudoenhancement correction
      with potentially significant benefits in clinical CTC examinations.

PMID- 19746795
TI  - A novel multithreshold method for nodule detection in lung CT.
AB  - Multislice computed tomography (MSCT) is a valuable tool for lung cancer
      detection, thanks to its ability to identify noncalcified nodules of small size
      (from about 3 mm). Due to the large number of images generated by MSCT, there is
      much interest in developing computer-aided detection (CAD) systems that could
      assist radiologists in the lung nodule detection task. A complete multistage CAD
      system, including lung boundary segmentation, regions of interest (ROIs)
      selection, feature extraction, and false positive reduction is presented. The
      selection of ROIs is based on a multithreshold surface-triangulation approach.
      Surface triangulation is performed at different threshold values, varying from a
      minimum to a maximum value in a wide range. At a given threshold value, a ROI is
      defined as the volume inside a connected component of the triangulated
      isosurface. The evolution of a ROI as a function of the threshold can be
      represented by a treelike structure. A multithreshold ROI is defined as a path on
      this tree, which starts from a terminal ROI and ends on the root ROI. For each
      ROI, the volume, surface area, roundness, density, and moments of inertia are
      computed as functions of the threshold and used as input to a classification
      system based on artificial neural networks. The method is suitable to detect
      different types of nodules, including juxta-pleural nodules and nodules connected
      to blood vessels. A training set of 109 low-dose MSCT scans made available by the
      Pisa center of the Italung-CT trial and annotated by expert radiologists was used
      for the algorithm design and optimization. The system performance was tested on
      an independent set of 23 low-dose MSCT scans coming from the Pisa Italung-CT
      center and on 83 scans made available by the Lung Image Database Consortium
      (LIDC) annotated by four expert radiologists. On the Italung-CT test set, for
      nodules having a diameter greater than or equal to 3 mm, the system achieved 84%
      and 71% sensitivity at false positive/scan rates of 10 and 4, respectively. For
      nodules having a diameter greater than or equal to 4 mm, the sensitivities were
      97% and 80% at false positive/scan rates of 10 and 4, respectively. On the LIDC
      data set, the system achieved a 79% sensitivity at a false positive/scan rate of
      4 in the detection of nodules with a diameter greater than or equal to 3 mm that
      have been annotated by all four radiologists.

PMID- 19746796
TI  - Variations of lung density and geometry on inhomogeneity correction algorithms: a
      Monte Carlo dosimetric evaluation.
AB  - This work contributed the following new information to the study of inhomogeneity
      correction algorithm: (1) Evaluation of lung dose calculation methods as a
      function of lung relative electron density (rhoe,lung) and treatment geometry and
      (2) comparison of doses calculated using the collapsed cone convolution (CCC) and
      adaptive convolution (AC) in lung using the Monte Carlo (MC) simulation with the
      EGSnrc-based code. The variations of rhoe,lung and geometry such as the position
      and dimension of the lung were studied with different photon beam energies and
      field sizes. Three groups of inhomogeneous lung phantoms, namely, "slab,"
      "column," and "cube," with different positions, volumes, and shapes of lung in
      water as well as clinical computed tomography lung images were used. The
      rhoe,lung in each group of phantoms vary from 0.05 to 0.7. 6 and 18 MV photon
      beams with small (4 x 4 cm2) and medium (10 x 10 cm2) field sizes produced by a
      Varian 21 EX linear accelerator were used. This study reveals that doses in the
      inhomogeneous lung calculated by the CCC match well with those by AC within +/-
      1%, indicating that the AC, with an advantage of shorter computing times (three
      to four times shorter than CCC), is a good substitute for CCC. Comparing the CCC
      and AC to MC in general, significant dose deviations are found when the rhoe,lung
      is < or =0.3. The degree of deviation depends on the photon beam energy and field
      size and is relatively large when high-energy photon beams with small fields are
      used. For penumbra widths (20%-80%), the CCC and AC agree well with MC for the
      slab and cube phantoms with the lung volumes at the central beam axis (CAX).
      However, deviations (>2 mm) occur in the column phantoms, with two lung volumes
      separated by a unit density column along the CAX in the middle using the 18 MV
      beam with 4 x 4 cm2 field for rhoe,lung < or =0.1. This study provides new
      dosimetric data to evaluate the impact of the variations of rhoe,lung and
      geometry on dose calculations in inhomogeneous media using CCC and AC.

PMID- 19746797
TI  - Spectral optimization for measuring electron density by the dual-energy computed
      tomography coupled with balanced filter method.
AB  - Dual-energy computed tomography (DECT) has the potential for measuring electron
      density distribution in a human body to predict the range of particle beams for
      treatment planning in proton or heavy-ion radiotherapy. However, thus far, a
      practical dual-energy method that can be used to precisely determine electron
      density for treatment planning in particle radiotherapy has not been developed.
      In this article, another DECT technique involving a balanced filter method using
      a conventional x-ray tube is described. For the spectral optimization of DECT
      using balanced filters, the author calculates beam-hardening error and air kerma
      required to achieve a desired noise level in electron density and effective
      atomic number images of a cylindrical water phantom with 50 cm diameter. The
      calculation enables the selection of beam parameters such as tube voltage,
      balanced filter material, and its thickness. The optimized parameters were
      applied to cases with different phantom diameters ranging from 5 to 50 cm for the
      calculations. The author predicts that the optimal combination of tube voltages
      would be 80 and 140 kV with Tb/Hf and Bi/Mo filter pairs for the 50-cm-diameter
      water phantom. When a single phantom calibration at a diameter of 25 cm was
      employed to cover all phantom sizes, maximum absolute beam-hardening errors were
      0.3% and 0.03% for electron density and effective atomic number, respectively,
      over a range of diameters of the water phantom. The beam-hardening errors were
      1/10 or less as compared to those obtained by conventional DECT, although the
      dose was twice that of the conventional DECT case. From the viewpoint of beam
      hardening and the tube-loading efficiency, the present DECT using balanced
      filters would be significantly more effective in measuring the electron density
      than the conventional DECT. Nevertheless, further developments of low-exposure
      imaging technology should be necessary as well as x-ray tubes with higher outputs
      to apply DECT coupled with the balanced filter method for clinical use.

PMID- 19746798
TI  - Understanding and controlling the effect of lossy raw data compression on CT
      images.
AB  - The requirements for raw data transmission through a CT scanner slip ring,
      through the computation system, and for storage of raw CT data can be quite
      challenging as scanners continue to increase in speed and to collect more data
      per rotation. Although lossy compression greatly mitigates this problem, users
      must be cautious about how errors introduced manifest themselves in the
      reconstructed images. This paper describes two simple yet effective methods for
      controlling the effect of errors in raw data compression and describe the impact
      of each stage on the image errors. A CT system simulator (CATSIM, GE Global
      Research Center, Niskayuna, NY) was used to generate raw CT datasets that
      simulate different regions of human anatomy. The raw data are digitized by a 20
      bit ADC and companded by a log compander. Lossy compression is performed by
      quantization and is followed by JPEG-LS (lossless), which takes advantage of the
      correlations between neighboring measurements in the sinogram. Error feedback, a
      previously proposed method that controls the spatial distribution of
      reconstructed image errors, and projection filtering, a newly proposed method
      that takes advantage of the filtered backprojection reconstruction process, are
      applied independently (and combined) to study their intended impact on the
      control and behavior of the additional noise due to the compression methods used.
      The log compander and the projection filtering method considerably reduce image
      error levels, while error feedback pushes image errors toward the periphery of
      the field of view. The results for the images are a compression ratio (CR) of 3
      that keeps peak compression errors under 1 HU and a CR of 9 that increases image
      noise by only 1 HU in common CT applications. Lossy compression can substantially
      reduce raw CT data size at low computational cost. The proposed methods have the
      flexibility to operate at a wide range of compression ratios and produce
      predictable, object-independent, and often imperceptible image artifacts.

PMID- 19746799
TI  - Four-dimensional (4D) image reconstruction strategies in dynamic PET: beyond
      conventional independent frame reconstruction.
AB  - In this article, the authors review novel techniques in the emerging field of
      spatiotemporal four-dimensional (4D) positron emission tomography (PET) image
      reconstruction. The conventional approach to dynamic PET imaging, involving
      independent reconstruction of individual PET frames, can suffer from limited
      temporal resolution, high noise (especially when higher frame sampling is
      introduced to better capture fast dynamics), as well as complex reconstructed
      image noise distributions that can be very difficult and time consuming to model
      in kinetic parameter estimation tasks. Various approaches that seek to address
      some or all of these limitations are described, including techniques that utilize
      (a) iterative temporal smoothing, (b) advanced temporal basis functions, (c)
      principal components transformation of the dynamic data, (d) wavelet-based
      techniques, as well as (e) direct kinetic parameter estimation methods. Future
      opportunities and challenges with regards to the adoption of 4D and higher
      dimensional image reconstruction techniques are also outlined.

PMID- 19746800
TI  - Kilovoltage stereotactic radiosurgery for age-related macular degeneration:
      assessment of optic nerve dose and patient effective dose.
AB  - Age-related macular degeneration (AMD) is a leading cause for vision loss for
      people over the age of 65 in the United States and a major health problem
      worldwide. Research for new treatments of the wet form of the disease using
      kilovoltage stereotactic radiosurgery is currently underway at Oraya
      Therapeutics, Inc. In the present study, the authors extend their previous
      computational stylized model of a single treated eye [Med. Phys. 35, 5151-5160
      (2008)] to include full NURBS-based reference head phantoms of the adult male and
      female using anatomical data from ICRP Publication 89. The treatment was
      subsequently modeled in MCNPX 2.5 using a 1 x 1 x 1 mm3 voxelized version of the
      NURBS models. These models incorporated several organs of interest including the
      brain, thyroid, salivary glands, cranium, mandible, and cervical vertebrae. A
      higher resolution eye section at 0.5 x 0.5 x 0.5 mm3 voxel resolution was
      extracted from the head phantoms to model smaller eye structures including the
      macula target, cornea, lens, vitreous humor, sclera/retina layer, and optic
      nerve. Due to lack of literature data on optic nerve pathways, a CT imaging study
      was undertaken to quantify the anatomical position of the optic nerve. The
      average absorbed doses to the organs of interest were below generally accepted
      thresholds for radiation safety. The estimated effective dose was 0.28 mSv which
      is comparable to diagnostic procedures such as a head radiograph and a factor of
      10 lower than a head CT scan.

PMID- 19746801
TI  - Contrast sensitivity of digital imaging display systems: contrast threshold
      dependency on object type and implications for monitor quality assurance and
      quality control in PACS.
AB  - The American Association of Physicists in Medicine Task Group 18 has published
      standards and quality control (QC) guidelines to ensure consistency and optimal
      quality for digital image display systems (DIDSs). In many of these recommended
      QC tests, static test patterns that contain low-contrast objects are often used
      to assess and validate the quality of a DIDS. These low-contrast objects often
      have the shape of circular disks or squares with sharp edges, neither of which
      resemble most of the diagnostic findings in medical images. On the other hand,
      circular objects with fuzzy boundaries bear a closer resemblance to lung nodules
      in chest radiography and masses in mammography; thus, they may be more clinically
      relevant in assessing display system quality. In this article human observers'
      contrast sensitivities of circular objects with sharp edges and those with fuzzy
      ones were investigated. The contrast thresholds of human viewers using a consumer
      grade color LCD monitor and a medical-grade monochrome LCD monitor were measured
      for objects of various sizes displayed against uniform backgrounds with various
      luminance levels. Contrast-detail curves for circular objects with sharp edges
      and those with fuzzy boundaries were measured and compared. It was found that
      contrast thresholds for objects with fuzzy boundaries were higher (i.e., the
      objects were more difficult to detect) than those with sharp edges. Objects with
      fuzzy boundaries were potentially more sensitive in distinguishing quality
      differences among image display devices and thus may be a better QC measurement
      in detecting subtle deterioration in image display devices.

PMID- 19746802
TI  - Variations in proton scanned beam dose delivery due to uncertainties in magnetic
      beam steering.
AB  - The purpose of this work was to develop a method to calculate and study the
      impact of fluctuations in the magnetic field strengths within the steering
      magnets in a proton scanning beam treatment nozzle on the dose delivered to the
      patient during a proton therapy treatment. First, an analytical relationship
      between magnetic field uncertainties in the steering magnets and the resulting
      lateral displacements in the position of the delivered scanned beam "dose spot"
      was established. Next, using a simple 3D dose calculation code and data from a
      validated Monte Carlo model of the proton scanning beam treatment nozzle, the
      uniform dose delivery to a 3D treatment volume was calculated. The dose
      distribution was then recalculated using the calculated lateral displacements due
      to magnetic field fluctuations to the proton pencil beam position. Using these
      two calculated dose distributions, the clinical effects of the magnetic field
      fluctuations were determined. A deliberate displacement of four adjacent spots
      either toward or away from each other was used to determine the "maximum" dose
      impact, while a random displacement of all spots was used to establish a more
      realistic clinical dose impact. Changes in the dose volume histogram (DVH) and
      the presence of hot and cold spots in the treatment volume were used to quantify
      the impact of dose-spot displacement. A general analytical relationship between
      magnetic field uncertainty and final dose-spot position is presented. This
      analytical relationship was developed such that it can be applied to study
      magnetic beam steering for any scanned beam nozzle design. Using this
      relationship the authors found for the example beam steering nozzle used in this
      study that deliberate lateral displacements of 0.5 mm or random lateral
      displacements of up to 1.0 mm produced a noticeable dose impact (5% hot spot) in
      the treatment volume. A noticeable impact (3% decrease in treatment volume
      coverage) on the DVH was observed for random displacements of up to 1.5 mm. For
      the scanning nozzle studied in this work, these displacement values correlated
      with an uncertainty value of 2.04% in the magnetic field values of the nozzle
      steering magnets. The authors conclude that fluctuations in the dose-spot
      delivery caused by uncertainty in the magnet fields used for beam steering could
      have clinically significant effects on the delivered dose distribution. Due to
      differences in the design and implementation of proton beam scanning nozzles at
      different treatment facilities, the effects of magnetic field fluctuations of
      dose delivery should be evaluated and understood for each specific nozzle design
      during clinical commissioning of the treatment nozzle.

PMID- 19746803
TI  - Development of a scatter correction technique and its application to HDR 192Ir
      multicatheter breast brachytherapy.
AB  - This article introduces a scatter correction (SC) technique for high-dose-rate
      (HDR) 192Ir brachytherapy dose calculations in the absence of a full scatter
      environment near the skin. The technique uses dosimetry data derived by Monte
      Carlo (MC) simulations for the Nucletron microSelectron v2 HDR 192Ir source. The
      data include the primary and scatter components of the radial dose function and
      the anisotropy function in addition to a SC table. The dose to a point of
      interest for each dwell position is estimated by first calculating the primary
      and scatter doses in an infinite water phantom. The scatter dose is then scaled
      by a SC factor that depends on the distances between the point of interest, the
      dwell positions, and the body contour of the patient. SC calculations in water
      phantoms of three different shapes, as well as computed tomography-based
      geometries of 18 multicatheter breast patients, are compared with Task Group 43
      (TG-43) and PTRAN_CT MC calculations. The SC calculations show improvement over
      TG-43 for all test cases while taking 50% longer to run. The target and skin
      doses for the breast patient plans are unaffected by tissue inhomogeneities, as
      indicated by an agreement better than 1% between the SC and MC results. On
      average, TG-43 overestimates the target coverage by 2% and the dose to the
      hottest 0.1 cm3 (D0.1 cc) of the skin by 5%. The low-density lung causes the lung
      and heart D0.1 cc to differ by up to 3% for the SC method and by 2%-5% for TG-43
      compared with MC calculations. The SC technique is suitable for HDR 192Ir dose
      calculations near the skin provided that the dose is nearly unperturbed by
      internal inhomogeneities. It has been validated for multicatheter breast
      brachytherapy.

PMID- 19746804
TI  - Dose response of CaF2:Tm to charged particles of different LET.
AB  - Thermoluminescent dosimeters are well established for performing calibrations in
      radiotherapy and for monitoring dose to personnel exposed to low linear energy
      transfer (LET) ionizing radiation. Patients undergoing light ion therapy and
      astronauts engaged in space flight are, however, exposed to radiation fields
      consisting of a mix of low- and high-LET charged particles. In this study, glow
      curves from CaF2:Tm chips were examined after exposure to various electron and
      ion beams. The annealing and readout procedures for these chips were optimized
      for these beams. After a 10 min prereadout annealing at 100 degrees C, the
      optimized glow curve samples the light output between 95 and 335 degrees C with a
      heating rate of 2 degrees C/s. The ratio of the integral of the glow curve under
      peaks 4-6 to the integral under peak 3 was approximately 0.9 for electrons, 1.0
      for entrance protons, 1.6 for peak protons, and 2.2 for entrance carbon, silicon,
      and iron ions. The integral light output per unit dose in water for the iron
      exposures was about half as much as for the electron exposures. The peak-area
      ratio can be used to determine a dose response factor for different LET
      radiations.

PMID- 19746805
TI  - High-speed dynamic 3D photoacoustic imaging of sentinel lymph node in a murine
      model using an ultrasound array.
AB  - Noninvasive photoacoustic sentinel lymph node (SLN) mapping with high spatial
      resolution has the potential to improve the false negative rate and eliminate the
      use of radioactive tracers in SLN identification. In addition, the demonstrated
      high spatial resolution may enable physicians to replace SLN biopsy with fine
      needle aspiration biopsy, and thus reduce the risk of associated morbidity. The
      primary goal of this study is to demonstrate the feasibility of high-speed 3D
      photoacoustic imaging of the uptake and clearance dynamics of Evans blue dye in
      SLNs. The photoacoustic imaging system was developed with a 30 MHz ultrasound
      array and a kHz repetition rate laser system. It acquires one 3D photoacoustic
      image of 166 B-scan frames in 1 s, with axial, lateral, and elevational
      resolutions of 25, 70, and 200 microm, respectively. With optic-fiber based light
      delivery, the entire system is compact and is convenient to use. Upon injection
      of Evans blue, a blue dye currently used in clinical SLN biopsy, SLNs in mice and
      rats were accurately and noninvasively mapped in vivo using our imaging system.
      In our experiments, the SLNs were found to be located at approximately 0.65 mm
      below the skin surface in mice and approximately 1.2 mm in rats. In some cases,
      lymph vessels and lymphatic valves were also imaged. The dye dynamics-
      accumulation and clearance--in SLNs were quantitatively monitored by sequential
      3D imaging with temporal resolution of as high as approximately 6 s. The
      demonstrated capability suggests that high-speed 3D photoacoustic imaging should
      facilitate the understanding of the dynamics of various dyes in SLNs and
      potentially help identify SLNs with high accuracy.

PMID- 19746806
TI  - Assessment of radiation doses to cardiologists during interventional
      examinations.
AB  - The accuracy of two on line dosimetric techniques was investigated for the
      estimation of cardiologist doses. The first technique involves the establishment
      of a database relating the cardiologist extremity doses to patient DAP values.
      Doses of nine cardiologists were measured together with patient doses during the
      interventional cardiac examinations of 166 patients for this purpose. Data were
      collected from five cardiology departments. The mean of the eye, thyroid, waist,
      right-left wrist, and right-left leg doses per procedure were measured as 72.4
      (31.6-107.1), 68.5 (13.3-174.6), 11.2 (0.9-28.4), 67.8 (21.9-120.3) to 216 (52.7
      425.4), and 137 (51.4-386.2) to 384 (135-1168.3) microGy/procedure. The effective
      doses were calculated according to the use of protection tools and a mean value
      of 12.14 (1.2-30.2) microSv/procedure was found. The ratios of staff dose to
      patient DAP were found to be within the range of 0.14-3.75 for each procedure. In
      the second method, cardiologist doses were calculated and compared with the
      measured values. Scatter doses were measured at the positions of cardiologists
      from Rando phantom exposures using similar conditions with patient procedures for
      this purpose. The parameters obtained from these exposures and patient
      examinations were used to calculate the doses to cardiologists.

PMID- 19746808
TI  - Quantitative megavoltage radiation therapy dosimetry using the storage phosphor
      KCl: Eu2+.
AB  - This work, for the first time, reports the use of europium doped potassium
      chloride (KCl:Eu2+) storage phosphor for quantitative megavoltage radiation
      therapy dosimetry. In principle, KCl:Eu2+ functions using the same
      photostimulatated luminescence (PSL) mechanism as commercially available
      BaFBr0.85I0.15:Eu2+ material that is used for computed radiography (CR) but
      features a significantly smaller effective atomic number--18 versus 49--making it
      a potentially useful material for nearly tissue-equivalent radiation dosimetry.
      Cylindrical KCl:Eu2+ dosimeters, 7 mm in diameter and 1 mm thick, were fabricated
      in-house. Dosimetric properties, including radiation hardness, response
      linearity, signal fading, dose rate sensitivity, and energy dependence, were
      studied with a laboratory optical reader after irradiation by a linear
      accelerator. The overall experimental uncertainty was estimated to be within +/
      2.5%. The findings were (1) KCl:Eu2+ showed satisfactory radiation hardness.
      There was no significant change in the stimulation spectra after irradiation up
      to 200 Gy when compared to a fresh dosimeter, indicating that this material could
      be reused at least 100 times if 2 Gy per use was assumed, e.g., for patient
      specific IMRT QA. (2) KCl:Eu2+ exhibited supralinear response to dose after
      irradiation from 0 to 800 cGy. (3) After x ray irradiation, the PSL signal faded
      with time and eventually reached a fading rate of about 0.1 % /h after 12 h. (4)
      The sensitivity of the dosimeter was independent of the dose rate ranging from 15
      to 1000 cGy/min. (5) The sensitivity showed no beam energy dependence for either
      open x ray or megavoltage electron fields. (6) Over-response to low-energy
      scattered photons was comparable to radiographic film, e.g., Kodak EDR2 film. By
      sandwiching dosimeters between low-energy photon filters (0.3 mm thick lead
      foils) during irradiation, the over-response was reduced. The authors have
      demonstrated that KCl:Eu2+ dosimeters have many desirable dosimetric
      characteristics that make the material conducive to radiation therapy dosimetry.
      In the future, a large-area KCl:Eu2+-based CR plate with a thickness of the order
      of a few microns, created using modern thin film techniques, could provide a
      reusable, quantitative, high-resolution two-dimensional dosimeter with minimal
      energy dependence.

PMID- 19746807
TI  - Automatic analysis of medial temporal lobe atrophy from structural MRIs for the
      early assessment of Alzheimer disease.
AB  - The purpose of this study is to develop a software for the extraction of the
      hippocampus and surrounding medial temporal lobe (MTL) regions from T1-weighted
      magnetic resonance (MR) images with no interactive input from the user, to
      introduce a novel statistical indicator, computed on the intensities in the
      automatically extracted MTL regions, which measures atrophy, and to evaluate the
      accuracy of the newly developed intensity-based measure of MTL atrophy to (a)
      distinguish between patients with Alzheimer disease (AD), patients with amnestic
      mild cognitive impairment (aMCI), and elderly controls by using established
      criteria for patients with AD and aMCI as the reference standard and (b) infer
      about the clinical outcome of aMCI patients. For the development of the software,
      the study included 61 patients with mild AD (17 men, 44 women; mean age +/-
      standard deviation (SD), 75.8 years +/- 7.8; Mini Mental State Examination (MMSE)
      score, 24.1 +/- 3.1), 42 patients with aMCI (11 men, 31 women; mean age +/- SD,
      75.2 years +/- 4.9; MMSE score, 27.9 +/- 1.9), and 30 elderly healthy controls
      (10 men, 20 women; mean age +/- SD, 74.7 years +/- 5.2; MMSE score, 29.1 +/-
      0.8). For the evaluation of the statistical indicator, 150 patients with mild AD
      (62 men, 88 women; mean age +/- SD, 76.3 years +/- 5.8; MMSE score, 23.2 +/-
      4.1), 247 patients with aMCI (143 men, 104 women; mean age +/- SD, 75.3 years +/-
      6.7; MMSE score, 27.0 +/- 1.8), and 135 elderly healthy controls (61 men, 74
      women; mean age +/- SD, 76.4 years +/- 6.1). Fifty aMCI patients were evaluated
      every 6 months over a 3 year period to assess conversion to AD. For each
      participant, two subimages of the MTL regions were automatically extracted from
      T1-weighted MR images with high spatial resolution. An intensity-based MTL
      atrophy measure was found to separate control, MCI, and AD cohorts. Group
      differences were assessed by using two-sample t test. Individual classification
      was analyzed by using receiver operating characteristic (ROC) curves. Compared to
      controls, significant differences in the intensity-based MTL atrophy measure were
      detected in both groups of patients (AD vs controls, 0.28 +/- 0.03 vs 0.34 +/-
      0.03, P < 0.001; aMCI vs controls, 0.31 +/- 0.03 vs 0.34 +/- 0.03, P < 0.001).
      Moreover, the subgroup of aMCI converters was significantly different from
      controls (0.27 +/- 0.034 vs 0.34 +/- 0.03, P < 0.001). Regarding the ROC curve
      for intergroup discrimination, the area under the curve was 0.863 for AD patients
      vs controls, 0.746 for all aMCI patients vs controls, and 0.880 for aMCI
      converters vs controls. With specificity set at 85%, the sensitivity was 74% for
      AD vs controls, 45% for aMCI vs controls, and 83% for aMCI converters vs
      controls. The automated analysis of MTL atrophy in the segmented volume is
      applied to the early assessment of AD, leading to the discrimination of aMCI
      converters with an average 3 year follow-up. This procedure can provide
      additional useful information in the early diagnosis of AD.

PMID- 19746809
TI  - Multimodality vascular imaging phantoms: a new material for the fabrication of
      realistic 3D vessel geometries.
AB  - Multimodality vascular flow phantoms provide a way of testing the geometric
      accuracy of clinical scanners and optimizing acquisition protocols with easy
      reproducibility of experimental conditions. This article presents a
      stereolithography method combined with a lost-material casting technique that
      eliminates metal residues of cerrolow (a low temperature melting point metallic
      alloy) left within irregular vessel lumens after casting. These residues
      potentially cause image artifacts especially in magnetic resonance angiography or
      flow disturbance. Geometrical accuracies of constructed lumens with isomalt, the
      proposed material, ranged from 3.3% to 5.7% for vessel diameters of 1.8-7.9 mm,
      which are comparable to those of lumens constructed with cerrolow that had better
      accuracies varying from 1.1% to 4.1% (p<0.02). Examples of geometries mimicking
      diseased arteries such as an aorta with stenosed renal arteries and an iliac
      artery with multiple stenoses are presented. This sugar-based isomalt material,
      combined with phantom designs having fiducial markers visible in digital
      subtraction angiography, computed tomography angiography, magnetic resonance
      angiography, and ultrasound [Med. Phys. 31, 1424-1433 (2004)], makes easier the
      fabrication of complex realistic and accurate replicas of pathological vessels
      with lumen irregularities.

PMID- 19746810
TI  - An alternative VMAT with prior knowledge about the type of leaf motion utilizing
      projection method for concave targets.
AB  - The authors present an alternative approach to inverse planning optimization and
      apply it to volumetric modulated are therapy (VMAT) in one rotation with a prior
      knowledge about the type of leaf motions. The optimization is based on the
      projection theorem in inner product spaces. MLC motion is directly considered in
      the optimization, thus avoiding leaf segmentation characteristic of IMRT
      optimization. In this work they realize the method for concave irregular targets
      encompassing an organ at risk leading to a repetitive MLC motion pattern.
      Applying the projection theorem leads to a noniterative optimization method and
      reduces to solving few systems of linear equations with small numbers of
      dimensions. The solution of the inverse problem is unique, and false minima are
      naturally excluded. They divided the full rotation into about 50 short arc
      segments and for each segment decomposed dose into separate contributions related
      to stages of MLC motion. This results generally in an inverse problem with just
      four free parameters per arc segment. Practically three degrees of freedom will
      be used for the purpose of a constant angular speed of the gantry. Therefore the
      total number of degrees of freedom for a 3D problem is about 3 x 50 x number of
      collimator leaf pairs for irradiating the whole target volume in one rotation.
      Two 2D and one 3D concave target volumes are applied for a slice by slice
      optimization. A 6 MV photon beam model is used, including realistic scattering
      and attenuation, and a maximal leaf velocity of 3 cm/s is regarded. The resulting
      dose distributions cover the PTVs very well and have maxima at about 108% of dose
      in the PTVs. The OAR is spared very strong in all cases. As a result of
      optimization, the MLC apertures are repetitively opening and closing and can be
      interpreted in an intuitive way. Applying the projection method for this
      knowledge-based VMAT delivery scheme for concave target volumes is an alternative
      technique for dose optimization. There are several properties, such as uniqueness
      of MLC motions and their continuous dependence on geometry and prescribed dose,
      that make this approach interesting to inverse planning. This method is still in
      an investigational stage, but promising results are presented. In future work it
      will be extended directly (without conceptual changes) in several directions to
      be more clinically applicable.

PMID- 19746811
TI  - A small-signal approach to temporal modulation transfer functions with exposure
      rate dependence and its application to fluoroscopic detective quantum efficiency.
AB  - The detective quantum efficiency (DQE) is a metric widely used in radiography to
      quantify system performance and as a surrogate measure of patient "dose
      efficiency." It has been applied previously to fluoroscopic systems with the
      introduction of a temporal correction factor. Calculation of this correction
      factor relies on measurements of the temporal modulation transfer function (MTF).
      However, the temporal MTF is often exposure-rate dependent, violating a necessary
      Fourier linearity requirement. The authors show that a Fourier analysis is
      appropriate for fluoroscopic systems if a "small-signal" approach is used. Using
      a semitransparent edge, a lag-corrected DQE is described and measured for an x
      ray image intensifier-based fluoroscopic system under continuous (non-pulsed)
      exposure conditions. It was found that results were equivalent for both rising
      and falling-edge profiles independent of edge attenuation when effective
      attenuation was in the range of 0.1-0.6. This suggests that this range is
      appropriate for measuring the small-signal temporal MTF. In general, lag was
      greatest at low exposure rates. It was also found that results obtained using a
      falling-edge profile with a radiopaque edge were equivalent to the small-signal
      results for the test system. If this result is found to be true generally, it
      removes the need for the small-signal approach. Lag-corrected DQE values were
      validated by comparison with radiographic DQE values obtained using very long
      exposures under the same conditions. Lag was observed to inflate DQE measurements
      by up to 50% when ignored.

PMID- 19746812
TI  - A clinically feasible method to estimate pharmacokinetic parameters in breast
      cancer.
AB  - Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) is the MRI
      technique of choice for detecting breast cancer, which can be roughly classified
      as either quantitative or semiquantitative. The major advantage of quantitative
      DCE-MRI is its ability to provide pharmacokinetic parameters such as volume
      transfer constant (Ktrans) and extravascular extracellular volume fraction (ve).
      However, semiquantitative DCE-MRI is still the clinical MRI technique of choice
      for breast cancer diagnosis due to several major practical difficulties in the
      implementation of quantitative DCE-MRI in a clinical setting, including (1) long
      acquisition necessary to acquire 3D T1(0) map, (2) challenges in obtaining
      accurate artery input function (AIF), (3) long computation time required by
      conventional nonlinear least square (NLS) fitting, and (4) many illogical values
      often generated by conventional NLS method. The authors developed a new analysis
      method to estimate pharmacokinetic parameters Ktrans and ve from clinical DCE-MRI
      data, including fixed T1(0) to eliminate the long acquisition for T1(0) map and
      "reference region" model to remove the requirement of measuring AIF. Other
      techniques used in our analysis method are (1) an improved formula to calculate
      contrast agent (CA) concentration based on signal intensity of SPGR data, (2) FCM
      clustering-based techniques for automatic segmentation and generation of a
      clustered concentration data set (3) an empirical formula for CA time course to
      fit the clustered data sets, and (4) linear regression for the estimation of
      pharmacokinetic parameters. Preliminary results from computer simulation and
      clinical study of 39 patients have demonstrated (1) the feasibility of their
      analysis method for estimating Ktrans and ve from clinical DCE-MRI data, (2)
      significantly less illogical values compared to NLS method (typically less than
      1% versus more than 7%), (3) relative insensitivity to the noise in DCE-MRI data;
      (4) reduction in computation time by a factor of more than 30 times compared to
      NLS method on average, (5) high statistic correlation between the method used and
      NLS method (correlation coefficients: 0.941 for Ktrans and 0.881 for ve), and (6)
      the potential clinical usefulness of the new method.

PMID- 19746813
TI  - Acceleration of high resolution temperature based optimization for hyperthermia
      treatment planning using element grouping.
AB  - In regional hyperthermia, optimization is useful to obtain adequate applicator
      settings. A speed-up of the previously published method for high resolution
      temperature based optimization is proposed. Element grouping as described in
      literature uses selected voxel sets instead of single voxels to reduce
      computation time. Elements which achieve their maximum heating potential for
      approximately the same phase/amplitude setting are grouped. To form groups,
      eigenvalues and eigenvectors of precomputed temperature matrices are used. At
      high resolution temperature matrices are unknown and temperatures are estimated
      using low resolution (1 cm) computations and the high resolution (2 mm)
      temperature distribution computed for low resolution optimized settings using
      zooming. This technique can be applied to estimate an upper bound for high
      resolution eigenvalues. The heating potential of elements was estimated using
      these upper bounds. Correlations between elements were estimated with low
      resolution eigenvalues and eigenvectors, since high resolution eigenvectors
      remain unknown. Four different grouping criteria were applied. Constraints were
      set to the average group temperatures. Element grouping was applied for five
      patients and optimal settings for the AMC-8 system were determined. Without
      element grouping the average computation times for five and ten runs were 7.1 and
      14.4 h, respectively. Strict grouping criteria were necessary to prevent an
      unacceptable exceeding of the normal tissue constraints (up to approximately 2
      degrees C), caused by constraining average instead of maximum temperatures. When
      strict criteria were applied, speed-up factors of 1.8-2.1 and 2.6-3.5 were
      achieved for five and ten runs, respectively, depending on the grouping criteria.
      When many runs are performed, the speed-up factor will converge to 4.3-8.5, which
      is the average reduction factor of the constraints and depends on the grouping
      criteria. Tumor temperatures were comparable. Maximum exceeding of the constraint
      in a hot spot was 0.24-0.34 degree C; average maximum exceeding over all five
      patients was 0.09-0.21 degree C, which is acceptable. High resolution temperature
      based optimization using element grouping can achieve a speed-up factor of 4-8,
      without large deviations from the conventional method.

PMID- 19746814
TI  - Effective DQE (eDQE) and speed of digital radiographic systems: an experimental
      methodology.
AB  - Prior studies on performance evaluation of digital radiographic systems have
      primarily focused on the assessment of the detector performance alone. However,
      the clinical performance of such systems is also substantially impacted by
      magnification, focal spot blur, the presence of scattered radiation, and the
      presence of an antiscatter grid. The purpose of this study is to evaluate an
      experimental methodology to assess the performance of a digital radiographic
      system, including those attributes, and to propose a new metric, effective
      detective quantum efficiency (eDQE), a candidate for defining the efficiency or
      speed of digital radiographic imaging systems. The study employed a geometric
      phantom simulating the attenuation and scatter properties of the adult human
      thorax and a representative indirect flat-panel-based clinical digital
      radiographic imaging system. The noise power spectrum (NPS) was derived from
      images of the phantom acquired at three exposure levels spanning the operating
      range of the clinical system. The modulation transfer function (MTF) was measured
      using an edge device positioned at the surface of the phantom, facing the x-ray
      source. Scatter measurements were made using a beam stop technique. The eDQE was
      then computed from these measurements, along with measures of phantom attenuation
      and x-ray flux. The MTF results showed notable impact from the focal spot blur,
      while the NPS depicted a large component of structured noise resulting from use
      of an antiscatter grid. The eDQE was found to be an order of magnitude lower than
      the conventional DQE. At 120 kVp, eDQE(0) was in the 8%-9% range, fivefold lower
      than DQE(0) at the same technique. The eDQE method yielded reproducible estimates
      of the system performance in a clinically relevant context by quantifying the
      inherent speed of the system, that is, the actual signal to noise ratio that
      would be measured under clinical operating conditions.

PMID- 19746815
TI  - Image-based dual energy CT using optimized precorrection functions: a practical
      new approach of material decomposition in image domain.
AB  - Dual energy CT (DECT) measures the object of interest using two different x-ray
      spectra in order to provide energy-selective CT images or in order to get the
      material decomposition of the object. Today, two decomposition techniques are
      known. Image-based DECT uses linear combinations of reconstructed images to get
      an image that contains material-selective DECT information. Rawdata-based DECT
      correctly treats the available information by passing the rawdata through a
      decomposition function that uses information from both rawdata sets to create
      DECT specific (e.g., material-selective) rawdata. Then the image reconstruction
      yields material-selective images. Rawdata-based image decomposition generally
      obtains better image quality; however, it needs matched rawdata sets. This means
      that physically the same lines need to be measured for each spectrum. In today's
      CT scanners, this is not the case. The authors propose a new image-based method
      to combine mismatched rawdata sets for DECT information. The method allows for
      implementation in a scanner's rawdata precorrection pipeline or may be used in
      image domain. They compare the ability of the three methods (image-based standard
      method, proposed method, and rawdata-based standard method) to perform material
      decomposition and to provide monochromatic images. Thereby they use typical
      clinical and preclinical scanner arrangements including circular cone-beam CT and
      spiral CT. The proposed method is found to perform better than the image-based
      standard method and is inferior to the rawdata-based method. However, the
      proposed method can be used with the frequent case of mismatched data sets that
      exclude rawdata-based methods.

PMID- 19746816
TI  - Noise aliasing and the 3D NEQ of flat-panel cone-beam CT: effect of 2D/3D
      apertures and sampling.
AB  - The ability to tune an imaging system to be optimal for a specific task is an
      essential component of image quality. This article discusses the ability to tune
      the noise-equivalent quanta (NEQ) of cone-beam computed tomography (CBCT) by
      managing noise aliasing through binning of data at different points in the
      reconstruction cascade. The noise power spectrum, modulation transfer function,
      and NEQ for CBCT are calculated using cascaded systems analysis. Binning is
      treated as a modular process, insertable between any two stages (in both the 2D
      projection domain and in the 3D reconstruction domain), consisting of the
      application of an aperture, followed by the resampling of data (which introduces
      noise aliasing). Several conditions were examined to demonstrate the validity of
      the model and to describe the effect on the image quality of some common
      reconstruction and visualization techniques. It was found that when downsampling
      data for increased reconstruction speed, binning in 2D results in a superior low
      frequency NEQ, while binning in 3D results in a superior high-frequency NEQ.
      Furthermore, visualization procedures such as slice averaging were found not to
      degrade the NEQ provided the sampling interval is unchanged. Finally methods for
      reducing noise aliasing by oversampling are examined, and a method to eliminate
      noise aliasing without increasing reconstruction time is proposed. These results
      demonstrate the ease with which the NEQ of CBCT can be modified and thus
      optimized for specific tasks and show how such analysis can be used to improve
      image quality.

PMID- 19746817
TI  - Commissioning and evaluation of an extended SSD photon model for PINNACLE3: an
      application to total body irradiation.
AB  - Total body irradiations (TBIs) are unusual radiation therapy techniques used to
      treat specific hematological diseases. Most TBI techniques use extended source to
      patient distances [source-to-skin distance (SSD)] to provide lateral or
      anteroposterior irradiations. Those techniques differ from one institution to the
      other since they need to be customized to accommodate for local material
      constraints. However, with those unusual techniques come additional challenges
      for dose calculation. The purpose of this study was to obtain an accurate (better
      than 4%) dose calculation model for extended source-to-skin distance (eSSD)
      treatment techniques, which will be used for TBI planning. The studied dynamic
      TBI technique has special aspects (eSSD, beam spoiler, large field, and out of
      field dose contribution) that need to be considered in dose calculation. The
      first part of this study presents an eSSD beam model commissioning in PINNACLE3
      and its validation. The second part looks at the comparison between two dose
      calculation algorithms, the 3D pencil beam and the superposition-convolution
      algorithms implemented in THERAPLAN PLUS and PINNACLE3, respectively. A regular
      linac beam was commissioned in each treatment planning system and an additional
      dedicated TBI beam model was implemented in PINNACLE3. The comparison results
      indicate that the quality of the TBI treatment greatly depends on the treatment
      planning system and its beam commissioning. The superposition-convolution
      algorithm (PINNACLE3) provides a better dose calculation tool for TBI than the 3D
      pencil beam algorithm (THERAPLAN PLUS) with a maximum mean error of 2.2% on a
      dynamic treatment. The TBI specific beam model of PINNACLE3 (ESSP-P3) also
      improves the dose calculation. The maximum difference between calculations and
      measurements (depth doses and beam profiles) was 2% except for extreme cases
      (build-up region and depth of 20 cm) where the error was higher. Output factor
      determination and the dose contribution outside the primary beam weaknesses were
      found in PINNACLE3. Methods are proposed to overcome these limitations. With the
      correction method applied, the TBI specific beam model allows a maximum mean
      error of -0.68% on a dynamic treatment. Accurate TBI dose computation
      necessitates a good dose calculation algorithm combined with a realistic beam
      model. Inappropriate dose calculation could lead to an important over- or
      underdose estimation. No perfect algorithm and beam model were found, but methods
      are proposed to overcome some of the limitations. Those methods are simple and
      can be used for other eSSD treatment types.

PMID- 19746818
TI  - Comment on "Monte Carlo evaluation of the convolution/superposition algorithm of
      Hi-Art tomotherapy in heterogeneous phantoms and clinical cases" [Med. Phys. 36,
      1566-1575 (2009)].

PMID- 19746819
TI  - Brain death: can it be resuscitated?
AB  - Why is a patient with a destroyed brain considered dead rather than moribund and
      irreversibly comatose? The world has been grappling with this question for the
      past four decades with little success. The recently released white paper of the
      President's Council on Bioethics is in many respects a refreshing, thoughtful,
      and comprehensive reexamination of this complex topic. It offers a very helpful
      analysis of the major positions on the determination of death, and it proffers a
      creative new solution of its own. Unfortunately, the new solution does not put
      the problem to rest, but the humility with which the council discusses its own
      position and the honesty with which it confronts the consequences of being wrong
      alone make this report a very commendable document.

PMID- 19746820
TI  - Controversies in the determination of death: the philosophical debate.

PMID- 19746821
TI  - Brief Amicus Curiae in Robert Baxter versus State of Montana.

PMID- 19746822
TI  - Other people's lives: reflections on medicine, ethics, and euthanasia.

PMID- 19746823
TI  - [Causes of death among pilots: "acute myocardial infarction"--are the present
      examination methods for airworthiness sufficient?].
AB  - The European Union plans to harmonize the aviation requirements, in particular
      the flight crew licensing requirements. On 23 May 2007, the German Federal
      Ministry of Transport, Building and Urban Affairs published the Flight Crew
      Licensing Requirements, which are based on the Joint Aviation Requirements,
      Flight Crew Licensing 3, Amendment 5. These guidelines also list the examination
      methods to be used for testing the medical fitness of pilots. In this Amendment
      some examinations which were part of the routine tests before JAR-FCL3 became
      effective have been deleted, e.g. the exercise ECG. This article presents two
      cases from the autopsy material of the Institute of Legal Medicine in Hanover and
      discusses the problems associated with the new examination guidelines.

PMID- 19746824
TI  - [Lethal intoxication while driving a car].
AB  - This report concerns a passenger car crash, which at first looked like a case of
      multiple trauma resulting in the death of the pinned-in driver. Conspicuous was a
      cuff that had been applied to the left forearm. No significant injuries could be
      determined during the autopsy of the corpse. The forensic toxicology results
      showed lethal toxic concentrations of the painkiller pethidine, which suggests
      that the driver had applied a lethal dose of the medication immediately before
      the collision as part of a complex suicide.

PMID- 19746825
TI  - [Cable tie used for suicidal ligature strangulation--a case report].
AB  - Based on a case of self-strangulation committed with two connected cable ties,
      criteria for the differentiation of homicidal and suicidal ligature strangulation
      are discussed. Differentiation may be difficult and demands close cooperation
      between the police and the forensic experts. Apart from the history and general
      circumstances of the case, not only the kind of strangulation, but also the
      presence of any concomitant injuries, the degree of congestion and any internal
      injuries are of relevance for the criminalistic evaluation. As self
      strangulations are rare, these cases demand special attention.

PMID- 19746826
TI  - [Has the transdermal patch gone up in smoke? A fatal fentanyl intoxication].
AB  - Recently, there has been an increase in fentanyl-related overdoses following
      administration of transdermal patches by the buccal, oral or intravenous route or
      via inhalation. A fatal intoxication is reported with clear evidence from
      toxicological analysis. However, the administration route and the fate of the
      patch remained elusive at the end of the investigations. Alcohol was present in
      the blood in small quantity (0.024%), whereas no other drug could be detected by
      basic strategies. Autopsy and microscopic examination failed to find sufficient
      evidence for a diagnosis. Fentanyl and norfentanyl were determined from body
      fluids and tissues by LC/MS/MS following liquid/liquid extraction. Both analytes
      were detectable in all specimens under investigation except muscle tissue where
      norfentanyl was absent. While the fentanyl concentration in the blood was
      considered potentially life-threatening on the basis of data obtained from living
      persons and fentanyl-related deaths, it was difficult to assess the other values
      because no comparative data were available. The history and circumstances of the
      case together with the toxicological findings suggest an intravenous or
      inhalative application of the patch. The latter assumption is supported by the
      fact that the body was found holding a cigarillo butt in his right hand. The case
      underlines the necessity to study fentanyl-related deaths more closely to allow a
      better interpretation of potential intoxications.

PMID- 19746827
TI  - [Determination of death and post-mortem examination on the high seas].
AB  - Usually death has to be determined by a physician. Deaths on board of ocean-going
      vessels confront the crew with special challenges, as on the high seas-
      especially in the container and cargo ship business--often no physician will be
      available and death has to be determined by medical laymen such as the captain or
      the medical officer. To document the determination of death, a "Provisional
      Certificate of Death on the High Seas" is presented. Moreover, an algorithm
      "Provisional Post-Mortem Examination on the High Seas" is presented to document
      the results and the practical performance of the external post-mortem examination
      by medical laymen on a ship. With the help of concrete procedural instructions
      medical laymen on board of sea-going vessels are to be enabled to determine the
      death of a human being beyond doubt, to perform a preliminary external post
      mortem examination and to store the corpse according to forensic requirements
      until the ship reaches a port and the body is delivered to the harbour physician.

PMID- 19746828
TI  - [Evaluation of injuries by means of photographs in a homicide (manslaughter or
      murder) barred by the statute of limitations].
AB  - Pursuant to Section 78 German Criminal Code, criminal offences under Section 220a
      (genocide) and Section 211 (murder) are not subject to a statute of limitations.
      To the extent that prosecution is subject to a statute of limitations, the period
      of limitation is thirty years in the case of acts punishable by imprisonment for
      life. After the expiration of the period of limitation, evidence and
      investigation records relevant for the offence may no longer be available. Once a
      homicide is statute-barred, main proceedings may be opened only, if the elements
      of murder are present. The problems arising from the statute of limitations are
      discussed on the basis of a case on which the author had to give an export
      opinion. The homicide was committed in Amsterdam in 1967. In 2004, after the
      period of limitation had expired in The Netherlands and--as far as manslaughter
      is concerned, also in the Federal Republic of Germany--a meanwhile 60-year-old
      man accused himself of having committed the offence (manual strangulation of a
      tied male). After the expiration of the statute of limitations the results of the
      police investigations and the autopsy report were no longer available. How the
      offence might have been committed and whether the elements of murder were present
      therefore had to be discussed on the basis of still available photographs of the
      crime scene and the victim. After studying these pieces of evidence, the criminal
      court decided that the accused had actually committed a voluntary homicide, but
      that it was no longer ascertainable, if the elements of murder were fulfilled.
      The issues relevant to legal medicine are presented against the background of the
      problems associated with the statute of limitations.

PMID- 19746829
TI  - [Infanticide by throwing the child from the 10th floor of a building].
AB  - Childbirth after denial or concealment of pregnancy has an increased risk of
      mortality for both mother and child. Interdisciplinary cooperation between
      professional groups is needed to explore the psychological and criminological
      aspects of infanticide. The case of a primipara mother, who threw her mature and
      viable newborn from the 10th floor of a high-rise building shortly after a
      concealed pregnancy, is reported. Forensic medical issues, as well as the
      characteristics of the offence and the perpetrator, are described.

PMID- 19746830
TI  - [Behavior problems and identification of mental states in preschoolers].
AB  - Aim of the study is to present a method to map the ability of children to
      identify emotions and intentions in emotionally relevant situations (intentional
      and emotional reflectiveness). Moreover we analyze interrelation between this
      ability and behavior problems. Therefore we administered Story Stem Interviews
      with 70 children and added demand questions focusing emotions and intentions of
      diverse characters within the child constructed stories. All the given answers we
      displayed on a six-ary scale. To review the clinical relevance we correlated this
      measure with questionnaire-based behavior screenings by educators in
      kindergarten. We found correlations between behavior problems and especially
      answers to emotion questions (emotional reflectiveness). We regard this as
      evidence that the ability to identify emotions and intentions in others has an
      important protective function even in childhood.

PMID- 19746831
TI  - [The potential performance of developmental screenings in kindergarten.
      Characteristics and circulation of currently available instruments in Germany].
AB  - The German institutions of elementary education, such as the kindergarten, are to
      perform developmental assessments for pre-school children in order to address
      specific need for interventions. Currently available assessment tools for the use
      by kindergarten staff were collected and compared according to scientific,
      economic and practical usability criteria based upon research and users
      expectations. 20 assessment tools were found in the German psychology database
      PSYNDEX, in publications, Internet, and in 45 interviews with experts from the
      largest supplier organizations of kindergartens. In addition to interviews and
      publications, criteria for the exclusion and the comparison of instruments were
      derived from basic methodological texts on test quality and from 10 interviews of
      kindergarten headmasters in Hamburg. Among the 48 descriptive characteristics of
      the screening instruments, 24 well-definable criteria were used for a comparison.
      The instruments varied widely in scope (developmental dimensions covered),
      efficiency (number of tasks and application time required), and practical
      usability. For most tools, including the most popular ones, psychometric quality
      is weak, not documented or dubious, and many tools neglect requirements of
      practical usability. Conclusions concerning the improved construction of
      instruments and the support of their implementation and practical relevance are
      proposed.

PMID- 19746832
TI  - [School refusal and psychiatric disorders in childhood and adolescence: findings
      from an outpatient sample of a psychiatric "school refusal ambulance"].
AB  - Based on a review of medical reports, a sample of 89 patients of a specialized
      school refusal outpatient unit of the Department of Child and Adolescent
      Psychiatry in Essen, Germany, is described. Variables included psychiatric
      diagnoses and treatment recommendations as well as individual and family
      characteristics such as type of school absence (school refusal vs. truancy),
      intelligence, anxiety, school career, parental occupational status, and parental
      divorce. Furthermore, differences between three groups of patients (anxious
      school refusers, truants, mixed school refusers) were explored. The results
      showed a high prevalence of psychiatric disorders and associated risk factors in
      the sample. Although some of the expected differences between the groups were
      obtained, the results yielded much overlap between anxious school refusers and
      truants and thus tended to stress the similarities among children who refuse to
      attend school.

PMID- 19746833
TI  - [Evaluation of pedagogic effects: adaptation of goal attainment scales to the
      needs of a juvenile penal system].
AB  - In youth welfare quality management increasingly gains in importance over the
      last decades. Tools used for quality assurance have to be broadly acceptable in
      everyday practical work. To meet that precondition it is essential that everyday
      practice and the different problem situations of children and adolescents are
      accordingly represented by these assessment scales. On the other hand they also
      require good methodical quality and generalization, thus, allowing to provide
      information about the effectiveness in a multiplicity of different residential
      institutions. Therefore, goal attainment scales have to be adapted to specific
      pedagogic settings as well as to the particular clientele. However, universal
      goals of pedagogic processes should be assessed as well. At the university
      hospital of Ulm, department child and adolescent psychiatry and psychotherapy, a
      scale was developed to measure the attainment of social competence and individual
      goals (PadZi). With the intention of an application of these scales in youth
      forensic context within a project (MAZ) in Switzerland the scales were adapted
      and expanded based on qualitative interviews with experts from the forensic and
      educational fields. Interrater agreement was shown to be good.

PMID- 19746834
TI  - Pharmaceutical product development technologies based on the biopharmaceutical
      classification system.
AB  - Poor solubility and poor permeability account for many pharmacokinetic failures
      and about thirty percent of drug molecules are rejected due to pharmacokinetic
      failures. When poor pharmaceutical properties are discovered in development, the
      cost of bringing a potent, but poorly absorbable molecule to the product stage by
      formulation can become very high. Fast and reliable in vitro prediction
      strategies are needed to filter out problematic molecules at the earliest stage
      of discovery. This communication will consider recent developments in
      physiochemical profiles used to identify molecules with physical properties
      related to good oral absorption. FDA's biopharmaceutical classification system
      (BCS) is an attempt to rationalize the critical components related to oral
      absorption and utilization of these principles for selection of a suitable
      technology to serve the interests of the early stages of drug discovery.

PMID- 19746835
TI  - Development and validation of an HPLC method for determination of oleanolic acid
      content and partition of oleanolic acid in submicron emulsions.
AB  - The aim of this study was to develop and validate a simple HPLC method for the
      quantitative determination of the oleanolic acid (OA) content and partition
      coefficient of OA in a submicron emulsion-based formulation (SE-OA). A Diamonsil
      C18 (150 mm x 4.6 mm, 5 microm) column was eluted with a mobile phase consisting
      of methanol/water (95:5, v/v). The analyses were performed at 35 +/- 1 degrees C
      with a flow rate of 1.0 mL/min and variable wavelength detector (VWD) at 210 nm.
      The calibration curve was linear over a concentration range of 2-100 microg/mL
      with a correlation coefficient of 0.999. The LOD and LOQ were 0.1 and 1
      microg/mL, respectively. The individual spike recovery of OA ranged from 99.88 to
      100.28%. The percent relative standard deviations (% R.S.D.) of intra-day and
      inter-day analyses were less than 3.1%. The validation results confirmed that the
      method is specific, linear, accurate, precise, robust and sensitive for its
      intended use. The present method was successfully applied to the determination of
      the OA content and partition coefficient of OA in SE-OA during the early stage of
      formulation development.

PMID- 19746836
TI  - Enantiomeric LC separation of valsartan on amylose based stationary phase.
AB  - A simple, rapid and robust LC method was developed and validated for the
      enantiomeric separation of valsartan in bulk drug and formulation. The
      enantiomers of valsartan were resolved on a Chiralpak AD-H (amylose based
      stationary phase) column using a mobile phase consisting of n-hexane: 2-propanol:
      trifluoroacetic acid (85:15:0.2, v/v/v) at a flow rate of 1.0 mL/min. The
      resolution between the enantiomers was found to be not less than 3.2. The
      presence of trifluoroacetic acid in the mobile phase played an important role in
      enhancing chromatographic efficiency and resolution between the enantiomers. The
      calibration curve for the (R)-enantiomer showed excellent linearity over the
      concentration range of 600 ng/mL (LOQ) to 6000 ng/mL. The limit of detection and
      limit of quantification for the (R)-enantiomer were 200 and 600 ng/mL,
      respectively. The percentage recovery of the (R)-enantiomer ranged between 98.7
      to 100.05 % in bulk drug samples of valsartan. The proposed method was found to
      be suitable and accurate for quantitative determination of (R)-enantiomer in bulk
      drug substance.

PMID- 19746837
TI  - Omega-3 fatty acids-loaded lipid nanoparticles for patient-convenient oral
      bioavailability enhancement.
AB  - Omega-3 fatty acids are commonly used as food supplements not only for their
      positive effects on the blood lipid profile but also for their cardioprotective
      properties. The majority of the commercially available products is made out of
      fish oil. Apart from the unpleasant side effects, up to 10 capsules per day have
      to be taken by the patients. This article describes the development and
      characterisation of an alternative lipid nanoparticle delivery system, which has
      the potential to reduce side effects and enhance bioavailability.

PMID- 19746838
TI  - Influence of three different colloidal systems on the oxytetracycline-lecithin
      behavior.
AB  - Oxytetracycline (OTC) is a wide spectrum antibiotic, but it is known to be
      degradated when it is stored under adverse conditions. It is classified as short
      acting based on serum half-lives of 6-8 h. The stabilizing effect of colloidal
      carrier systems and their ability to sustain drug release for OTC was
      investigated using solid dispersion, liposomes and solid lipid nanoparticles with
      lecithin. Analysis of chemical stability showed that OTC is more resistant in
      colloid systems than in the free form. The characterization results show clear
      differences between the prepared systems. Release studies show that a sustained
      release is achieved when the OTC is formulated in these carriers.

PMID- 19746839
TI  - Topical administration of cyclosporin A in a solid lipid nanoparticle
      formulation.
AB  - Cyclosporin A (CsA)-loaded solid lipid nanoparticles (SLN) were developed for
      improved skin penetration. CsA-loaded SLN, prepared using a hot homogenization
      method, were nano-sized (about 73 nm) with a slightly negative surface charge
      (about -16 mV) and stable under physiological conditions regardless of CsA
      incorporation. In vitro permeation studies using murine skin mounted in the Franz
      type vertical diffusion assembly revealed that the skin permeation efficiency of
      CsA-loaded SLN was 2-fold higher than that of CsA-oil mixture in viable skin.
      Furthermore, topically administered CsA-loaded SLN relieved symptoms of atopic
      dermatitis (AD) in an in vivo murine model of AD by decreasing the T helper (Th)
      2 cell-related cytokines interleukin (IL)-4 and -5. These results suggest that
      SLN are effective drug carriers for topical delivery andthat CsA-loaded SLN can
      be therapeutically applied in allergy-related skin disorders.

PMID- 19746840
TI  - Physicochemical characteristics and oral bioavailability of andrographolide
      complexed with hydroxypropyl-beta-cyclodextrin.
AB  - A significant increase in solubility of andrographolide (AND), a slightly water
      soluble anti-inflammatory and antimicrobial drug, was achieved by inclusion with
      hydroxypropyl-beta-cyclodextrin (HP-beta-CD). The inclusion complex was prepared
      by solvent evaporation and characterized by the phase solubility method, X-ray
      diffractometry and differential scanning calorimetry. The solubility of AND
      increased linearly as a function of HP-beta-CD concentration, resulting in A(L)
      type phase solubility diagram. Molecular modeling calculations were used to
      foresee the possible orientations of AND inside the HP-beta-CD cavity. The in
      vitro dissolution profile showed a significant increase in dissolving rate and
      percent of the inclusion complex compared with uncomplexed drug. In vivo
      pharmacokinetic study showed that AUC(0-infinity) was 1.6-fold higher than that
      of AND suspension after oral administration. These results suggest that HP-beta
      CD inclusion system might be a promising formulation for the oral delivery of
      AND.

PMID- 19746841
TI  - Histamine interaction with Zn2+ and Cu2+ porphyrins.
AB  - Histamine may be present in biological fluids and in pharmaceutical dosage forms
      such as antiallergenic agents; when in excess, it causes a disorder called
      histaminosis. Many techniques have been developed to determine the concentration
      of this compound but the application of such methods is complicated and
      laborious, requiring expensive equipment and long times. A better alternative is
      to design chemical sensors. In the work reported here, six metalloporphyrins
      (Cu2+ or Zn2+) with different peripheral groups - benzoate, tosylate and
      carboxylate - were studied. The stability constants for these compounds were
      determined with histamine at different temperatures. Histamine is strongly bound
      to metallic porphyrins containing Cu2+ and Zn2+; however, the binding force does
      not depend exclusively on the metal center. Stabilization of the complex is
      strongly influenced, in some cases, by the lateral chains of the porphyrin. This
      possibility implies that this system can be very selective for this biogenic
      amine.

PMID- 19746842
TI  - Influence of grapefruit juice on the pharmacokinetics of diltiazem in Wistar rats
      upon single and multiple dosage regimens.
AB  - Drug efflux by intestinal P-glycoprotein (P-gp) is recognized as a significant
      biochemical barrier affecting oral absorption for a number of drugs apart from
      the cytochrome P450 3A enzyme. Various conflicting reports have been published
      regarding the effects of grapefruit juice (GFJ) on P-gp mediated drug efflux, in
      which GFJ has been shown to have no effect, as an inhibitor effect or activation
      of the enzyme. Therefore the present study's objective was to provide
      clarification of previous findings, adopting a two-way approach, involving both
      single dose and multiple dosage regimens. Diltiazem (DTZ) 15 mg/kg was
      administered concomitantly with 5 ml/kg of GFJ to one group (n = 6) of male
      Wistar rats and another group (n = 6) of animals were provided distilled water
      with DTZ (the control). A third group of rats was administered GFJ orally for six
      days and on seventh day GFJ and DTZ were administered concomitantly. The Cmax and
      AUC of DTZ were decreased significantly in the presence of multiple dose
      treatment of GFJ. These data were also decreased in presence of simultaneous
      treatment of single dose GFJ. In vitro metabolism studies and gut sac experiments
      were conducted in order to understand the mechanism involved. In the liver S9
      fraction prepared from the rats treated with multiple doses of GFJ, DTZ
      metabolism was significantly increased compared to the control. Furthermore, the
      amount of drug transported from the duodenum was reduced in GFJ treated rats
      compared to that of the control (1581.0 +/- 7.8 nM vs 1084.81 +/- 6.1 nM,
      respectively). Grapefruit juice was also reported to inhibit the organic anion
      transporting polypeptide (OATP), an influx transporter thus reducing the blood
      levels of OATP substrates which was evident from the in vitro studies. The amount
      of drug transported from the duodenum was reduced in the presence of pravastatin,
      a specific OATP inhibitor (1581.0 +/- 7.8 nM to 1265.0 +/- 5.5 nM). Oral single
      dose exposure to GFJ showed no effect on P-gp, whereas multiple dose
      administration of GFJ resulted in increased levels of P-gp expression and
      decreased levels of OATP, thus showing a varied effect on intestinal absorption,
      and therefore overcoming the inhibition of DTZ metabolism in rats.

PMID- 19746843
TI  - AVS-1357 inhibits melanogenesis via prolonged ERK activation.
AB  - In this study, we demonstrated that a derivative of imidazole, AVS-1357, is a
      novel skin-whitening compound. AVS-1357 was found to significantly inhibit
      melanin production in a dose-dependent manner; however, it did not directly
      inhibit tyrosinase. Furthermore, we found that AVS-1357 induced prolonged
      activation of extracellular signal-regulated kinase (ERK) and Akt, while it
      downregulated microphthalmia-associated transcription factor (MITF) and
      tyrosinase. It has been reported that the activation of ERK and/or Akt is
      involved in melanogenesis. Therefore, we examined the effects of AVS-1357 on
      melanogenesis in the absence or presence of PD98059 (a specific inhibitor of the
      ERK pathway) and/or LY294002 (a specific inhibitor of the Akt pathway). PD98059
      dramatically increased melanogenesis, whereas LY294002 had no effect.
      Furthermore, PD98059 attenuated AVS-1357 induced ERK activation, as well as the
      downregulation of MITF and tyrosinase. These findings suggest that the effects of
      AVS-1357 occur via downregulation of MITF and tyrosinase, which is caused by AVS
      1357-induced prolonged ERK activation. Taken together, our results indicate that
      AVS-1357 has the potential as a new skin whitening agent.

PMID- 19746844
TI  - Antiviral activity of Rhus aromatica (fragrant sumac) extract against two types
      of herpes simplex viruses in cell culture.
AB  - We report on the antiviral potency of an aqueous extract of root/stem bark of
      Rhus aromatica (fragrant sumac extract) against herpes simplex virus type 1 and
      type 2 in cell culture (RC-37 cells) using a plaque reduction assay. The extract
      exhibited a high level of anti-HSV activity with IC50-values of 0.0005% for HSV-1
      and 0.0043% for HSV-2 as well as high selectivity indices (SI) of 5400 for HSV-1
      and 628 for HSV-2. In order to determine the mode of antiviral action, the
      fragrant sumac extract was added at different times to the cells or viruses
      during the viral infection cycle. At maximum non-cytotoxic concentration (0.25%),
      plaque formation was significantly reduced by more than 99% when herpes simplex
      viruses were pretreated with the plant extract for 1 h prior to cell infection.
      When the host cells were pretreated with the fragrant sumac extract for 1 h prior
      to virus infection, the infectivity of viruses was reduced by 50% for HSV-1 but
      only moderately for HSV-2. No antiviral effect was seen when the plant extract
      was added to already infected host cells. Based on these findings the plant
      extract seems to interact not only with the viral envelope but also with the
      surface of the host cells impairing the ability of herpes simplex viruses to
      adsorb to and penetrate into the host cells. In conclusion, the aqueous fragrant
      sumac extract revealed a strong antiviral activity against HSV-1 and HSV-2 in
      vitro.

PMID- 19746845
TI  - Roots of Daphne gnidium L. inhibit cell proliferation and induce apoptosis in the
      human breast cancer cell line MCF-7.
AB  - Daphne gnidium L. is a well-known Moroccan plant with cancer-related
      ethnobotanical use. In order to systematically evaluate its potential activity in
      breast cancer, four extracts from this plant of different polarity were tested
      for their antiproliferative effects on MCF-7 cells. The second aspect of this
      study related to understanding the nature and mechanism of the antiproliferative
      effect. Results from a viability assay showed the potent antiproliferative
      capacity of the hexane (IC(50)-48 h: 630 +/- 16 microg/ml), dichloromethane
      (IC(50)-48 h: 112 +/- 7 microg/ml) and ethyl acetate extracts (IC(50)-48 h: 263
      +/- 9 microg/ml). On the other hand the methanol extract was inactive. LDH test
      revealed the cytotoxicity of the hexane extract as opposed to two others. The
      characterization of the ethyl acetate extract showed its dose-dependent pro
      apoptotic effect. Surprisingly, we observed that activation of the inducible
      cyclooxygenase-2 followed the kinetics of apoptosis development. On the other
      hand, the dichloromethane extract showed a distinct effect on COX-2 activity as a
      function of the used dose. A low dose seemed to inhibit COX-2 activity whereas a
      high dose seemed to increase it. These findings suggest that Daphne gnidium L.
      might be of potential chemopreventive interest. Other studies are in hand to
      isolate the active agents responsible for the antiproliferative effect.

PMID- 19746846
TI  - Antiatherogenic activity of Dendropanax morbifera essential oil in rats.
AB  - In Korea, Dendropanax morbifera Leveille (Araliaceae) is commonly used in
      traditional medicines for various diseases. We evaluated the hypolipidemic
      activity of D. morbifera essential oil (DMEO) in male Wistar rats (weight, 160 +/
      15 g) maintained on a high-cholesterol diet. DMEO was extracted by
      hydrodistillation and analyzed using gas chromatography/mass spectroscopy
      (GC/MS). The DMEO yield was 3.5%, and GC/MS analysis revealed that its major
      constituents were gamma-elemene (18.59%), tetramethyltricyclo hydrocarbons
      (10.82%), beta-zingiberene (10.52%), and beta-selinene (10.41%). Rats were orally
      administered DMEO at doses of 50, 100, and 200 mg kg(-1) d(-1) for 2 weeks. DMEO
      significantly and dose-dependently reduced the total cholesterol, triglyceride,
      and low-density lipoprotein cholesterol levels and significantly increased the
      high-density lipoprotein cholesterol levels. We conclude that D. morbifera has
      significant lipid-lowering effects and is a promising agent that should be
      considered in studies seeking new, safe, and effective natural cardioprotective
      agents.

PMID- 19746847
TI  - The paradox of scored tablets: a cost-saving risk.
AB  - One of the cornerstones of pharmacotherapy is the proper dose of medicine, which
      should ideally be tailored to the individual patient. However, even if clinically
      possible, this is economically not feasible as a too large number of different
      dosage strengths would be required. Therefore, a balance is required between the
      patient's benefit/risk and the cost to the individual and society on the other
      hand. Scored or splitted tablets were, and still are, often used strategies to
      these opposite interests, enabling more dose-flexibility, but also at the same
      time increasing the dose-variability as a consequence of the breaking process.
      The question of how to deal with this paradox was investigated by exploring the
      prevalence and classification of scored tablets as well as the cost-benefits. A
      strategy for clinical pharmacologists is presented to improve the outcome of this
      paradox.

PMID- 19746848
TI  - The Recovery Audit Contractors are rolling out: are you prepared?

PMID- 19746849
TI  - Questions surround OPPS on physician supervision.

PMID- 19746850
TI  - Hospital drops readmission rate for HF patients by 10%.

PMID- 19746852
TI  - Tips, common mistakes in getting survey-ready.

PMID- 19746851
TI  - Transitional care model proves its worth.

PMID- 19746853
TI  - Hematology and absence of hemoparasites in breeding common terns (Sterna hirundo)
      from Cape Cod, Massachusetts.
AB  - In June and July 1995, 98 breeding common terns (Sterna hirundo) were captured,
      weighed, and bled as a part of ongoing research on the population health and
      reproductive biology of this species of special concern. Packed cell volume,
      total and differential white blood cell counts, and blood smears were obtained.
      Blood smears from 75 terns were examined. No hemoparasites were found. There were
      some significant differences among hematologic parameters in birds from different
      islands, and between birds nesting earlier versus later in the season, but there
      were no significant differences associated with body mass, sex, or age. The
      absence of hemoparasites in the blood smears of these terns is noteworthy,
      especially because other studies of seabirds (including Charadriiformes) have
      revealed low prevalences of hematozoa.

PMID- 19746854
TI  - Standardization of some electrocardiographic parameters of captive leopard cats
      (Leopardus tigrinus).
AB  - Thirty-three captive leopard cats, Leopardus tigrinus, were anesthetized with
      xylazine (1-2 mg/kg) and ketamine (10 mg/kg), and electrocardiograph (ECG) tests
      were recorded in all leads with 1 cm = 1 mV sensibility and 25 mm/sec speed
      repeating DII lead at 50 mm/sec speed with the same sensibility. Results
      expressed by mean and standard deviation were: heart rate (HR) = 107 +/- 17
      (bpm); P-wave = 0.048 +/- 0.072 (s) x 0.128 +/- 0.048 (mV); PR interval = 0.101
      +/- 0.081 (s); QRS compound = 0.053 +/- 0.012 (s) x 1.446 +/- 0.602 (mV); QT
      interval = 0.231 +/- 0.028 (s); R-wave (CV6LL) = 1.574 +/- 0.527 (mV); R-wave
      (CV6LU) = 1.583 +/- 0.818 (mV); heart rhythm: normal sinus rhythm (15.2%), sinus
      rhythm with wandering pacemaker (WPM) (60.6%), sinus arrhythmia with WPM (24.2%);
      electric axis: between +30 degrees and +60 degrees (6.1%), +60 (6.1%), between
      +60 degrees and +90 degrees (57.6%), +90 degrees (9%), between +90 degrees and
      +120 degrees (21.2%); ST segment: normal (75.7%), elevation (18.2%), depression
      (6.1%); T-wave polarity (DII): positive (100%); T-wave (V10): absent (6.1%),
      negative (63.6%), positive (18.2%), and with interference (12.1%). Through ECG
      data comparison with other species, unique features of Leopardus tigrinus'
      (leopard cat) ECG parameters were detected. Some of the study animals presented
      with an R-wave amplitude that was indicative of left ventricle overload according
      to patterns for normal domestic cats (Felis cati). Echocardiographic exams
      revealed normal heart cavities' function and morphology. The aim of this study
      was to establish some electrocardiographic parameters of captive L. tigrinus.

PMID- 19746855
TI  - Evaluation of hematologic and biochemical values for convalescing seals from the
      coast of Maine.
AB  - Marine mammal researchers and veterinarians evaluate the health of individuals
      and populations by using observed ranges for blood values. The goal of this study
      was to establish observed ranges for dependent (0-4 week) and weanling (>4 week)
      harbor seal (Phoca vitulina) pups that were admitted for rehabilitation at the
      Marine Animal Lifeline in Portland, Maine from 1998-2003 and to record changes in
      hematologic and biochemical values as they convalesced. Blood values, measured
      both at admission to and release from rehabilitation, were quantitatively
      compared between these two groups. Of the 29 blood analytes measured in this
      study between dependent and weanling pups upon admission to rehabilitation, 14
      were significantly different including white blood cell (WBC), red blood cell
      (RBC), hemoglobin (Hb), hematocrit (HCT), platelets, lymphocytes, monocytes,
      potassium, chloride, CO2, total bilirubin, calcium, alanine transaminase (ALT),
      and alkaline phosphatase. Between admission and release, 14 analytes had
      significantly changed for dependent pups including RBC, Hb, HCT, mean cell volume
      (MCV), mean corpuscular hemoglobin (MCH), platelets, lymphocytes, monocytes,
      potassium, blood urea nitrogen (BUN), total protein, total bilirubin, alkaline
      phosphatase, and ALT. Between admission and release, 10 analytes had
      significantly changed for weanlings including RBC, MCV, neutrophils, eosinophils,
      potassium, chloride, anion gap, total protein, total bilirubin, and calcium. At
      the time of release, six parameters were significantly different between pups
      admitted as dependent and those admitted as weanlings including MCV, neutrophils,
      eosinophils, total protein, globulin, and albumin.

PMID- 19746856
TI  - Ocular bacterial flora, tear production, and intraocular pressure in a captive
      flock of Humboldt penguins (Spheniscus humboldti).
AB  - The purpose of this study was to determine normal ocular surface bacterial flora,
      tear production, and intraocular pressure in a captive flock of Humboldt
      penguins, Spheniscus humboldti. Twenty-eight healthy penguins were studied and
      equally divided between fresh- and saltwater habitats. The population consisted
      of 15 female and 13 male penguins, ranging from 3-20 years of age. Following
      complete ophthalmic exam, 4 penguins with cataracts were removed from the study.
      Eight penguins from each habitat were randomly selected for ocular surface
      aerobic bacterial culture. Corynebacterium spp. and Staphylococcus spp. were the
      most common isolates. Twenty-five organisms consisting of 17 species, and 15
      organisms consisting of 9 species, were identified in fresh- and saltwater
      groups, respectively. Tear production and intraocular pressures were evaluated on
      24 penguins with normal ocular exams. The range and mean (+/- standard deviation)
      tear production, measured with the Schirmer tear test, was 1-12 mm/min and 6.45
      mm/min +/- 2.9, respectively. The mean tear production for penguins housed in the
      freshwater habitat was greater (8.5 mm/min) than those in saltwater (4.8 mm/min).
      The range and mean (+/- standard deviation) intraocular pressure, measured by
      applanation tonometry using a Tono-Pen XL tonometer, was 10-27 mmHg and 20.36
      mmHg +/- 4.1, respectively. This data should be utilized as a reliable resource
      for those involved in avian and zoo medicine.

PMID- 19746857
TI  - Proliferative endometrial lesions in a group of Seba's short-tailed bats
      (Carollia perspicillata).
AB  - An unusually high prevalence of uterine changes was observed on necropsy in a
      group of 169 female Seba's short-tailed bats (Carollia perspicillata). In this
      case study, 27 animals were affected from 1997 to 2007, representing 16% of the
      group population. All bats were of an indeterminate age and originated from the
      same facility, but were housed in three different zoological institutions. Deaths
      occurred year round. Most animals were found dead, with no previous clinical
      signs. Clinical signs, when present, included a markedly distended abdomen,
      extended periods of time perched on the exhibit floor, lethargy, and anorexia.
      Histologic changes included florid segmental to diffuse endometrial hyperplasia
      and occasional hemorrhage and adenomyosis. The cause for this condition has not
      been determined.

PMID- 19746858
TI  - Health assessment of a spiny-tailed lizard (Uromastyx spp.) population in Abu
      Dhabi, United Arab Emirates.
AB  - A study was conducted to determine the health status of the free-living spiny
      tailed lizard (Uromastyx spp.) population at Wrsan, Al Ajban, Abu Dhabi, United
      Arab Emirates. A total of 90 spiny-tailed lizards, 61 males and 29 females, were
      examined from June to August 2006. Mean body weights were 1,564.4 g and 809.4 g
      for males and females, respectively. Mean body lengths were 62.1 cm and 49.4 cm
      for males and females, respectively. Fourteen lizards were found with
      abnormalities including abscesses, bite wounds, and deformed or missing tail
      ends, digits, or claws. Radiographic examination revealed osteomyelitis,
      arthritis, and healed fractures. Reference hematology and chemistry values were
      obtained from the 76 clinically normal lizards. Hemoparasitemia included possible
      new species of Karyolysus and Hepatozoon. The most common oropharyngeal organisms
      isolated were Escherichia coli, Providencia spp., and nonhemolytic
      Staphylococcus; and the most common cloacal organisms were E. coli, Proteus spp.,
      Providencia spp., and nonhemolytic Staphylococcus. Ascarids were the only
      endoparasites found. This is the first biomedical data published for the spiny
      tailed lizard.

PMID- 19746859
TI  - Shoulder dysplasia in koalas (Phascolarctos cinereus) at San Diego Zoo.
AB  - A radiographic study documented shoulder dysplasia (n = 43), with varying degrees
      of malformation of the supraglenoid and infraglenoid tubercles and the coracoid
      process, shallowing or loss of the glenoid cavity, flattening or loss of the
      humeral head, malformation of the greater and lesser tubercles, loss of the
      intertubercle groove, and humeral diaphyseal abnormalities, in northern koalas
      (Phascolarctos cinereus) in the San Diego Zoo (San Diego, California, USA)
      colony. Retrospectively, historic radiographs (n = 38) were examined where
      available. Prospectively, three standard views (lateral extended arm,
      ventrodorsal cranially positioned arms, and ventrodorsal caudally positioned
      arms) were imaged (n = 25). In all radiographs, shoulders were graded as normal,
      or mildly, moderately, or severely dysplastic. Although affected koalas typically
      do not exhibit clinical signs, degenerative joint disease may develop and
      clinical signs treated with nonsteroidal anti-inflammatory drugs. Where shoulder
      and hip radiographs were both available (n = 60), 92% of individuals had
      correlation between the degree of shoulder and hip dysplasia.

PMID- 19746860
TI  - Noninvasive monitoring of androgens in male Amazonian manatee (Trichechus
      inunguis): biologic validation.
AB  - The Amazonian manatee (Trichechus inunguis) is endemic in the Amazonian basin and
      is the only exclusively fresh water sirenian. Historically hunted on a large
      scale, this species is now considered endangered, and studies on the reproductive
      physiology are critical for the improvement of reproductive management of captive
      and wild populations of manatees. The aim of this study was to verify the
      viability of androgen measurement in saliva, lacrimal, urine, and fecal samples
      of the Amazonian manatee by conducting a hormone challenge. Two adult male
      manatees (A-1 and A-2) were submitted to an experimentation protocol of 12 day
      (D1 to D10). On D0, the animals received an intramuscular injection of
      gonadotropin-releasing hormone (GnRH)-analogue. Salivary, lacrimal, urinary, and
      fecal samples were collected daily (between 0800 hours and 0900 hours) and frozen
      at -20 degrees C until assayed. Fecal samples were lyophilized, extracted with
      80% methanol, and diluted in buffer before the radioimmunoassay (RIA). Urine
      samples underwent acid hydrolysis and were diluted in depleted bovine serum.
      Salivary and lacrimal samples were assayed without the extraction step. Hormonal
      assays were conducted with a commercial testosterone RIA kit. An androgen peak (>
      median + 2 interquartile range [IQR]) was observed in all matrices of both
      animals, although it was less prominent in the lacrimal samples of A-2. However,
      the fecal androgen peak (A-1 peak = 293.78 ng/g dry feces, median [IQR] = 143.58
      [32.38] ng/g dry feces; A-2 peak = 686.72 ng/g dry feces, median [IQR] = 243.82
      [193.16] ng/g dry feces) occurred later than urinary (A-1 peak = 648.16 ng/mg
      creatinine [Cr], median [IQR] = 23.88 [30.44] ng/mg Cr; A-2 peak = 370.44 ng/mg
      Cr, median [IQR] = 113.87 [117.73] ng/mg Cr) and salivary (A-1 peak = 678.89
      pg/ml, median [IQR] = 103.69 [119.86] pg/ml; A-2 peak = 733.71 pg/ml, median
      [IQR] = 262.92 [211.44] pg/ml) androgen peaks. These intervals appear to be
      correlated with the long digesta passage time in this species. The salivary and
      urinary peaks were closely associated. These results demonstrate that androgen
      concentrations in saliva, urine, or feces samples reflect reliably physiologic
      events and are a powerful tool for noninvasive reproductive monitoring of
      Amazonian manatees.

PMID- 19746861
TI  - Electrocardiography of the Asian elephant (Elephas maximus).
AB  - Electrocardiograms (ECGs) are infrequently performed on Asian elephants (Elephas
      maximus), and few studies have been reported in the literature. The aim of this
      study was to determine reference ranges of ECG parameters in Asian elephants and
      to ascertain if age, body weight, and position of the elephant significantly
      affected the ECG. Electrocardiograms were obtained from 27 captive, nonsedated
      apparently healthy Asian elephants while they were standing (ST), in right
      lateral recumbency (RL), and/or in left lateral recumbency (LL). Six-lead ECGs
      were obtained using novel clamps and long ECG cables (71 cm). From lead I,
      standard waveforms and intervals were analyzed, including PR interval, QT
      interval, ST segment, P, QRS, T, and U waves if they were present. One animal was
      determined to have a previously undiagnosed conduction abnormality and was not
      included in the study. Most elephants had a sinus arrhythmia in at least one
      position. With increasing age, there was a trend toward a slower heart rate and
      significantly longer P waves. Increasing body weight was significantly correlated
      with longer QT intervals and T waves with lower amplitude. Compared with
      measurements in ST, LL resulted in P waves and QRS complexes with shorter
      amplitude, U waves with greater amplitude, PR intervals with shorter duration,
      and an increased heart rate. Compared with measurements in LL, RL resulted in
      larger QRS complexes. U waves were most commonly detected in RL and LL. Mean
      electrical axis calculated in the frontal plane were as follows: standing range 
      125 to +141 degrees, mean -5 degrees; left lateral range -15 to +104 degrees,
      mean 27 degrees; right lateral range -16 to +78 degrees, mean 9 degrees. Position
      specific reference ranges should be used when interpreting ECGs, and clinicians
      must be aware of how age and body weight may affect the ECG.

PMID- 19746862
TI  - Carotid artery exteriorization in brown brocket deer (Mazama gouazoubira) for an
      experimental study of anesthesia.
AB  - This report evaluates the carotid artery exteriorization technique to allow
      repeated percutaneous artery catheterization in six brown brocket deer (Mazama
      gouazoubira). Repeated percutaneous catheterization of the carotid artery was
      possible for periods of 3 mo to obtain arterial blood and monitor arterial blood
      pressure of deer without risk of arterial rupture. The artery pulse was easily
      palpable for periods up to 15 mo. Postoperative complication and/or arterial
      damage was not observed.

PMID- 19746863
TI  - Cardiac evaluation of clinically healthy captive maned wolves (Chrysocyon
      brachyurus).
AB  - The objective of this project was to determine radiographic vertebral heart sizes
      and electrocardiographic (ECG) and echocardiographic measurements in healthy
      anesthetized maned wolves (Chrysocyon brachyurus). The wolves, housed at the
      White Oak Conservation and Smithsonian National Zoo Conservation and Research
      Centers, were being anesthetized for annual examinations. Cardiac auscultation,
      thoracic radiographs, a standard 6-lead ECG, and echocardiography were performed
      on the wolves while they were under general anesthesia. Thirteen maned wolves
      were evaluated: five males and eight females. Mean age was 6.4 +/- 4.4 years
      (range, 2-13 years). Mean weight was 26 +/- 2.95 kg (range, 22-32 kg). Low-grade
      systolic murmurs were auscultated in three of 13 maned wolves. Evaluation of ECGs
      revealed a sinus rhythm, with a QRS morphology, and mean electrical axis similar
      to domestic canines. Radiographic evaluation revealed a mean vertebral heart size
      of 8.27 +/- 0.48 (range, 7.9-8.6). In addition, the cardiac silhouette was seen
      to elongate, with an increase in sternal contact in older wolves.
      Echocardiography showed that mitral valve degenerative changes and insufficiency
      is likely common in older wolves. Visualization of physiologic regurgitation
      across the mitral and pulmonary valves was common in wolves of all ages. Left
      ventricular measurements were similar to those reported for healthy dogs, and
      several variables correlated well with body weight. Two wolves were found to have
      one to three heartworms in the right pulmonary artery, and degenerative mitral
      valve disease was determined in maned wolves older than 6 years of age. All of
      the wolves in this study were on heartworm preventative and tested negative for
      heartworm antigen at their annual examinations. The results of this study provide
      reference information for use in the cardiac evaluation of anesthetized maned
      wolves.

PMID- 19746864
TI  - Assessment of novel avian renal disease markers for the detection of experimental
      nephrotoxicosis in pigeons (Columba livia).
AB  - Renal disease is a major cause of illness in captive and wild avian species.
      Current renal disease markers (e.g., uric acid, blood urea nitrogen, and
      creatinine) are insensitive. Two endogenous markers, creatine and N-acetyl-beta-D
      glucosaminidase (NAG), were selected for study in the pigeon (Columba livia).
      Representative organs from four pigeons were surveyed to determine those
      exhibiting the highest level of each marker. In a separate study, NAG and
      creatine from plasma and urine were assayed before and after gentamicin (50 mg/kg
      twice daily), administration for up to 9 days. Observer-blinded pathologic
      scoring (five saline solution controls, 17 treated birds) was used to verify the
      presence of renal disease that corresponded to marker increases. The first study
      revealed that kidney tissue had the highest NAG activity (by approximately six
      times), and pectoral muscle had the most creatine (>900 times). In response to
      gentamicin, plasma creatine (>five times) and NAG increased (approximately six
      times), which paralleled uric acid (>10 times). Urine creatine (approximately 60
      times) and NAG increased dramatically (approximately 50 times) in response to
      gentamicin. In conclusion, NAG, especially in the urine, may be of value to
      noninvasively detect renal toxin exposures and to monitor potentially nephrotoxic
      drugs, and might be of value to screen free-ranging birds in large exhibits or in
      the wild by assaying fresh urate samples at feeding stations.

PMID- 19746865
TI  - Determination of lead and zinc concentrations in the blood and liver of the
      captive common green iguana (Iguana iguana).
AB  - Heavy metal toxicosis is a well-known phenomenon in wild, captive-animal, and
      domestic animal medicine. However, the occurrence among reptiles is not well
      documented. One reason for this is the lack of information regarding reference
      blood and tissue levels of heavy metals in reptiles. To determine normal blood
      lead, plasma zinc, and liver lead and zinc concentrations, blood and liver
      samples were collected from 4 adult and 16 juvenile, healthy green iguanas
      (Iguana iguana). Lead and zinc levels were measured using atomic absorption
      spectroscopy. Using the mean +/- two SD as the normal reference range, the
      present study suggests the following for captive common green iguana: 1) whole
      blood lead level: 0.06 +/- 0.06 microg/ml; 2) plasma zinc level: 2.68 +/- 1.66
      microg/ml; 3) liver lead level (wet-weight basis): <1.0 +/- 0.0 microg/g; 4)
      liver lead level (dry-weight basis): <3.0 +/- 0.0 microg/g; 5) liver zinc level
      (wet-weight basis): 24.9 +/- 11.6 microg/g; and 6) liver zinc level (dry-weight
      basis): 83.4 +/- 44.6 microg/g. These values are fairly consistent with published
      reference levels in other mammalian and avian species.

PMID- 19746866
TI  - Pharmacokinetics of marbofloxacin in loggerhead sea turtles (Caretta caretta)
      after single intravenous and intramuscular doses.
AB  - The disposition kinetics of marbofloxacin at a single dose of 2 mg/kg bodyweight
      were determined in a crossover trial with five clinically healthy loggerhead sea
      turtles (Caretta caretta) after i.v. and i.m. administration. Marbofloxacin
      plasma concentrations were determined by high-performance liquid chromatography
      (LOD/LOQ 0.05 microg/ml). Data were subjected to noncompartmental analysis. The
      integrated pharmacokinetic/pharmacodynamic variables showed that optimal area
      under the curve (AUC(0-24 h)): minimal inhibitory concentration (MIC) (>125) and
      Cmax: MIC (>8) ratios, as reported for concentration-dependent bactericidal
      antimicrobials (e.g., fluoroquinolones), were achievable with both a once daily
      i.v. or i.m. dose for microorganisms with MIC < or = 0.5 microg/ml, while a Cmax:
      MIC > 8 for MIC > or = 1 microg/ml was achievable only after the i.v.
      administration. The absence of adverse reactions in the animals after i.v. or
      i.m. administration of marbofloxacin and the favorable
      pharmacokinetic/pharmacodynamic properties after a single dose of 2 mg/kg suggest
      the possibility of its safe and effective clinical use in loggerhead sea turtles.

PMID- 19746867
TI  - Evaluation of oral itraconazole administration in captive Humboldt penguins
      (Spheniscus humboldti).
AB  - Aspergillus spp. fungal infections are the most common cause of morbidity and
      mortality in captive penguins. Itraconazole has been the drug of choice for both
      therapeutic and prophylactic treatment; however, the pharmacokinetic and
      pharmacodynamic parameters can be highly variable in different species, and it
      has not been evaluated in penguins. In this study, four preliminary steady-state
      trials were performed to compare two oral formulations of itraconazole
      (commercial capsules compared with generic bulk compounded powder) at two
      different dosages (6 or 12 mg/kg once a day) administered in fish to small groups
      of captive Humboldt penguins (Spheniscus humboldti). Building on this data, a
      final steady-state trial was performed with the use of a 7 mg/kg oral dosage
      twice a day of commercial capsules given in fish to a group of 15 penguins. With
      sparse sampling, blood was drawn for testing from small subsets of each treatment
      group at 4-7 time points in the 24-hr period after the final dose of itraconazole
      on day 14. Steady-state plasma concentrations of itraconazole and
      hydroxyitraconazole, the major metabolite, were determined by reverse phase high
      performance liquid chromatography with fluorescence detection. Treatment with the
      generic bulk compounded product resulted in plasma levels of itraconazole that
      were undetectable for 26 out of 30 blood samples, compared with seven out of 20
      blood samples for the commercial product at the same dosage. On the basis of
      study results, an estimated oral dosage of either 8.5 mg/kg twice a day or 20
      mg/kg once a day of the commercial itraconazole capsules given in fish would
      produce adequate steady-state therapeutic blood levels in Humboldt penguins.

PMID- 19746868
TI  - Prevalence and phylogenetic analysis of hepatitis B virus among nonhuman primates
      in Taiwan.
AB  - Hepatitis B virus (HBV) is a public health problem worldwide, and apart from
      infecting humans, HBV has been found in nonhuman primates. This study
      investigated the prevalence and phylogenetic analysis of hepatitis B virus (HBV)
      and hepatitis D virus (HDV) among nonhuman primates in Taiwan, an area where
      human HBV remains endemic. Serum samples from 286 captive nonhuman primates
      (i.e., 32 great apes [Pan troglodytes and Pongo pygmaeus], 42 gibbons [Hylobates
      sp. and Nomascus sp.], and 212 Cercopithecidae monkeys) were collected and tested
      for the presence of HBV- and HDV-specific serologic markers. None of the
      Cercopithecidae monkeys were reactive against serologic markers of HBV. In
      contrast, 21.9% (7/32) of great apes and 40.5% (17/42) of gibbons tested positive
      for at least one serologic marker of HBV. Of these, five gibbons were chronic HBV
      carriers, characterized by presence of HBV DNA and hepatitis B surface antigen in
      the serum. HBV DNA was also detected in the saliva of three of the chronic
      carries. None of these HBV carrier gibbons exhibited symptoms or significant
      change in serum clinical chemistry related to HBV infection. Phylogenetic
      analysis of the complete HBV genome revealed that gibbon viruses clustered with
      other HBV isolates of great apes and gibbons from Southeast Asia and separately
      from human-specific HBV. None of the HBV-infected animals were reactive against
      HDV. These findings indicate that HBV found in these animals is indigenous to
      their respective hosts and might have been introduced into Taiwan via the direct
      import of infected animals from Southeast Asia. To reduce the horizontal and
      vertical transmission of HBV in captive animals, the HBV carriers should be kept
      apart from uninfected animals.

PMID- 19746869
TI  - Polycystic kidney disease in the pygmy hippopotamus (Hexaprotodon liberiensis).
AB  - Polycystic kidney disease (PKD) was diagnosed at necropsy in a captive aged
      female pygmy hippopotamus (Hexaprotodon liberiensis), which presented with
      numerous cysts in both kidneys, the liver, and the duodenum and with one single
      cyst in the pancreas. There were no premonitory clinical signs of a nephropathy
      observed prior to its death. Similar findings were made in a male cage mate 6 mo
      later. Both animals had been wild caught. A literature review revealed that
      another seven cases of PKD have been reported in pygmy hippopotamuses, and an
      additional screening of records available from the international studbook for the
      species revealed yet another six cases. In all cases, aged females were affected,
      and in several instances, affected animals were related to each other. These
      patterns indicated familiar transmission similar that associated with PKD in
      humans and other animals. The disease, and especially the presumptive bias in
      diagnosis toward females, indicated that the male animal of this report was the
      first case of PKD reported in a male pygmy hippopotamus; thus, further
      investigation is warranted. The status of the kidneys with respect to PKD should
      be assessed (including histology) in every deceased pygmy hippopotamus, and
      whenever possible by ultrasonography in live animals.

PMID- 19746870
TI  - Positive skin and serologic test results of diagnostic assays for bovine
      tuberculosis and subsequent isolation of Mycobacterium interjectum in a pygmy
      hippopotamus (Hexaprotodon liberiensis).
AB  - A 20-yr-old male pygmy hippopotamus (Hexaprotodon liberiensis), weighing 250 kg,
      arrived at Zoological Society London Whipsnade Zoo (United Kingdom) from a
      captive collection in Portugal. A quarantine health check was performed including
      a comparative intradermal tuberculosis (IDTB) test. Assessment of the comparative
      IDTB test at 72 hr revealed a strong positive reaction at the bovine site. Serum
      was tested with a rapid immunochromatographic assay (TB STAT-PAK) and was
      positive for tuberculosis antibodies. The tuberculosis tests were repeated 6 wk
      later with the same positive test outcome. In addition, a broncho-alveolar lavage
      (BAL) was submitted for mycobacterial culture. The positive IDTB test and TB STAT
      PAK results were supported by multiantigen print immunoassay (MAPIA). Based on
      these results, the animal was suspected to be infected with Mycobacterium
      tuberculosis complex organisms and was euthanized. No gross or histologic signs
      of tuberculosis were found at postmortem examination. Mycobacterium interjectum
      was cultured from the BAL but not from necropsy samples. The antigens used in the
      TB STAT-PAK and MAPIA tests are reportedly specific for the M. tuberculosis
      complex, and so it is possible this animal presented with a latent case of
      tuberculosis or had a previous tuberculosis infection that resolved prior to
      testing. Cross-reactions with nontuberculous mycobacteria have been described
      with TB STAT-PAK and MAPIA tests. However, Western blotting analysis using serum
      from this animal did not recognize M. interjectum proteins of equivalent size to
      the M. tuberculosis-Mycobacterium bovis proteins recognized in the MAPIA. Thus,
      antigenic cross-reactivity with M. interjectum can be deemed less likely, but
      other nontuberculous mycobacterial proteins cannot be ruled out. It is therefore
      possible that false-positive reactions were obtained. These results highlight the
      difficulty of diagnosing tuberculosis in the absence of pathology and the
      presence of nontuberculous mycobacteria.

PMID- 19746871
TI  - Proventricular nematodiasis in wrinkled hornbills (Aceros corrugatus).
AB  - Three immature Sunda wrinkled hornbills (Aceros corrugatus) were diagnosed
      postmortem with proventricular spirurid nematodiasis. Concurrent severe
      disseminated larval granulomatosis in other visceral organs was considered
      contributory to mortality in each case. Clinical signs of nematodiasis were vague
      but generally consisted of weight loss, anorexia, and lethargy. Frequent
      antemortem fecal examinations were negative for spirurid eggs. In these present
      cases, based on routine histopathology, both prophylactic and empirically based
      therapeutic anthelmintic treatments had no evident benefit in the elimination of
      the proventricular nematodes. Spirurid nematodiasis may be an important cause of
      mortality in young hornbills.

PMID- 19746872
TI  - Echinococcus oligarthrus cystic hydatidosis in Brazilian agouti (Dasyprocta
      leporina).
AB  - Echinococcus oligarthrus hydatid cyst disease was diagnosed in two imported wild
      caught Brazilian agouti (Dasyprocta leporina). The cysts were found incidentally
      during routine examinations and never appeared to cause any apparent clinical
      signs. Identification of the cysts was confirmed via histopathology. Over a
      period of 2 yr, the cysts calcified but did not reabsorb. Treatment with
      praziquantal and albendazole did not appear to affect the cysts. Agoutis are
      intermediate hosts of E. oligarthrus in the wild, where jaguars (Panthera onca)
      and pumas (Puma concolor) act as definitive hosts. Caution is advised when
      working with E. oligarthrus-infected animals because of the zoonotic disease
      potential.

PMID- 19746873
TI  - PCR detection of ranavirus in adult anurans from the Louisville Zoological
      Garden.
AB  - Ranaviruses are known to cause mortality in a variety of anuran species and have
      the potential to significantly impact wild and captive frog populations. In this
      study, 16 captive frogs and toads from the Louisville Zoological Garden were
      examined for the presence of ranavirus; this group included 14 Cope's grey tree
      frogs (Hyla chrysoscelis), an American toad (Bufo americanus), and a southern
      toad (Bufo terrestris). All animals were wild caught and were evaluated via
      polymerase chain reaction (PCR), while animals that died were also assessed via
      histologic study to understand the role of ranaviral disease in these specimens.
      Of the animals that died, 82% were positive for ranavirus via PCR. Multiple swab
      samples collected over time from live tree frogs were positive for ranavirus via
      PCR. These findings reveal that ranaviral infection in captive adult anurans may
      occur without clinical signs or consistent histopathologic lesions.

PMID- 19746874
TI  - Successful transabdominal subxiphoid pericardiostomy to relieve chronic
      pericardial effusion in a Sumatran orangutan (Pongo abelli).
AB  - A 46-yr-old female Sumatran orangutan (Pongo abelli) was first diagnosed with
      pericardial effusion in July 2006. Pericardiocentesis performed in January 2007
      only provided short-term relief. In May 2007, a pericardial-peritoneal window was
      created using a transabdominal subxiphoid pericardiostomy technique, providing
      immediate and long-term relief. Seven months later, the orangutan was euthanized
      due to worsening heart failure, and no pericardial effusion was present.
      Transabdominal subxiphoid pericardiostomy offers a straightforward surgical
      approach that can provide significant relief in cases of chronic pericardial
      effusion in great apes.

PMID- 19746875
TI  - Paraparesis in a polar bear (Ursus maritimus) associated with West Nile virus
      infection.
AB  - A polar bear (Ursus maritimus) housed at the Toronto Zoo presented with acute
      onset, nonambulatory paraparesis. Physical examination 24 hr after onset was
      otherwise unremarkable, spinal radiographs looked normal, and blood tests
      indicated mild dehydration. With continued deterioration in its general
      condition, euthanasia was elected a day later. Necropsy did not reveal a cause
      for the major presenting clinical signs. Serum collected at the time of initial
      examination was positive for West Nile virus (WNV) antibodies in a serum
      neutralization assay and at the time of euthanasia was positive in both a
      competitive enzyme-linked immunosorbent assay and in a plaque reduction
      neutralization assay. The major microscopic finding was a mild-to-moderate
      nonsuppurative meningoencephalomyelitis. WNV was not detected by
      immunohistochemistry in brain or spinal cord or by real-time reverse
      transcription-polymerase chain reaction (RT-PCR) and cell culture of brain and
      kidney, but it was isolated and identified by RT-PCR in second passage cell
      culture of spleen. Retrospective immunohistochemistry on spleen revealed rare
      antigen-positive cells, probably macrophages. Prevention of exposure to
      potentially WNV-infected mosquitoes or vaccination of captive bears against WNV
      should be considered.

PMID- 19746876
TI  - Sepsis and disseminated intravascular coagulation in an eastern spiny softshell
      turtle (Apalone spinifera spinifera) with acute mycobacteriosis.
AB  - An adult, captive eastern spiny softshell turtle (Apalone spinifera spinifera)
      was examined for a 4-day history of lethargy and plastron discoloration. The
      turtle was obtunded and had pale mucous membranes, hemorrhagic nasal discharge,
      and petechiae on all limbs. The turtle was euthanized due to its grave condition.
      Necropsy revealed hemorrhagic coelomic effusion, petechiae on the serosal
      surfaces of the intestinal tract, and bilaterally hemorrhagic lungs. Histologic
      examination revealed numerous emboli of bacteria associated with fibrinocellular
      thrombi throughout the blood vessels of multiple tissues. The bacteria in the
      thrombi were slender bacilli that stained intensely acid fast. Culture of the
      coelomic fluid yielded Mycobacterium chelonae. Although mycobacteriosis in
      reptiles is typically a chronic, granulomatous disease, this case demonstrates
      that mycobacteriosis should be considered in reptiles presenting with acute,
      nongranulomatous disease. This case also describes clinically apparent hemorrhage
      due to disseminated intravascular coagulation, which is rarely described in
      chelonians.

PMID- 19746877
TI  - Articular gout and suspected pseudogout in a Basilisk lizard (Basilicus
      plumifrons).
AB  - A 9-yr-old male Basilisk lizard (Basilicus plumifrons) with a history of painful
      and limited mobility for approximately 4 mo, which had seemed to be more
      pronounced in the front limbs, was presented for necropsy. The animal had
      exhibited moderate weight loss and anorexia before euthanasia. Postmortem
      examination revealed yellow-to-white, soft-to-semifirm nodules within the
      periarticular fascia and musculature of the left and right shoulder joints, hip
      joints, and stifle joints. Several other joints, including the left and right
      tarsi, left and right elbow joints, and the left carpus had calcified, white
      material present on the articular surfaces. Histopathologic evaluation of
      representative sections of all organs and the joints confirmed tophaceous
      articular gout and articular pseudogout. The differentiation between articular
      gout and pseudogout was based on histologic appearance, histochemical staining
      for calcium, and birefringence under polarized light.

PMID- 19746878
TI  - Fungal keratitis in a gopher tortoise (Gopherus polyphemus).
AB  - A free-ranging gopher tortoise (Gopherus polyphemus) presented for trauma and
      blindness. Fibrinous exudate obscured visualization of the globes. This exudative
      crust extended from the conjunctival fornices through the palpebral fissure and
      was manually removed. Ophthalmic examination revealed bilateral corneal
      ulcerations and scarring and phthisis bulbi of the left globe. Histology of the
      crust revealed a necrotic conjunctivitis with intralesional fungal hyphae.
      Culture of the corneal ulcer of the left eye isolated moderate growth of a mixed
      fungal flora consisting of Curvularia sp. and Aspergillus sp. Miconazole
      ophthalmic solution was administered and the ulcers in both eyes healed, but
      corneal edema continued. After 2 mo of treatment with miconazole, tramadol,
      acetylcysteine, hypertonic saline ointment, artificial tears, and hypertonic
      saline flushes, the right eye was normal with only a small scar. The left eye
      remained phthisical. This is the first report of fungal keratitis in a wild
      reptile and a gopher tortoise.

PMID- 19746879
TI  - Sida carpinifolia (Malvaceae) poisoning in fallow deer (Dama dama).
AB  - A captive fallow deer (Dama dama) in a zoo was spontaneously poisoned after
      consumption of Sida carpinifolia. The paddock where cervids were kept was
      severely infested by S. carpinifolia. The deer developed a neurological syndrome
      characterized by muscular weakness, intention tremors, visual and standing-up
      deficits, falls, and abnormal behavior and posture. Because a severe mandibular
      fracture and the consequent deteriorating condition, it was euthanized. Main
      microscopic findings were swelling and multifocal cytoplasmic vacuolation in the
      Purkinje cells. The cytoplasm of multiple cells of the cerebellum, especially the
      Purkinje cells, stained with the lectins Concanavalia ensiformis, Triticum
      vulgaris, and succinylated Triticum vulgaris. Diagnostic possibilities such as
      bovine diarrhea virus, rabies, and transmissible spongiform encephalopathy were
      excluded. The report focuses on the risk of maintaining S. carpinifolia
      populations in zoo enclosures of wild herbivores.

PMID- 19746880
TI  - Capillaria hepatica in Puma concolor: first report in Brazil.
AB  - Capillaria hepatica was detected by histopathologic diagnosis in two cougars that
      were shot in April 2008 in Painel, Santa Catarina, Brazil. Macroscopic analysis
      of their livers revealed the presence of diffuse granulomas, and the
      histopathologic analysis indicated the presence of C. hepatica eggs, surrounded
      by mononuclear inflammatory cell infiltrate, small foci of necrosis, and mild-to
      moderate fibrosis. This is the first report of C. hepatica in cougars (Puma
      concolor) in Brazil.

PMID- 19746881
TI  - ["Great was the name of Galen". The physician's self-portrayal in his works].
AB  - Galen, besides being one of the most important and productive doctors and medical
      writers of Antiquity, was also a dedicated and efficient self-promoter. This
      paper uses characteristic examples to illustrate how Galen, according to his own
      writings, combined anatomical and physiological demonstrations with scientific
      discussion, polemics and a confident self-portrayal in his public appearances.

PMID- 19746882
TI  - [The enchanting word chymiatria--and the attractiveness of the training of
      physicians at Marburg, 1608-1620: a somewhat different way to calculate the
      frequency of students].
AB  - The number of medical students at the University of Marburg in the early 17th
      century was so far thought to amount scarcely to a handful, tending towards zero.
      In contrast to that, this paper identifies for the time from 1600 to 1620 80
      students of medicine, 73 just for the twelve years from 1608 to 1620. Almost a
      third of these, 23, also received their doctorate in Marburg, whereas most of the
      others went to other universities for this purpose (Basel in particular) or ended
      their studies as a candidatus medicinae. The highest total number of students of
      a single year amounts to 28 in 1616. The reason for this rise to one of the most
      attractive medical faculties in the German-speaking countries was a completely
      new beginning with the professors Nicolaus Braun, Johannes Hartmann (till 1618),
      and Heinrich Petraeus (till 1620) following the vacancy of all three
      professorships of medicine. Of these professors Braun represented the traditional
      Galenic medicine, whereas Hartmann and Petraeus acted as academic protagonists of
      the modem chymiatria (the chemical, paracelsian or hermetic medicine), that they
      made their task to harmonize with the conventional medicine. To that purpose
      teaching was supplemented by Petraeus with a cleverly devised intensive system of
      disputing and responding of the college of Nosologia and by Hartmann with a
      practical training of the students in a chemical laboratory. The new kind of
      teaching attracted students from many other German and European countries,
      primarily from Silesia, whereas the number of local students from Hessia remained
      at its previous very low level.

PMID- 19746883
TI  - [Experiments on living subjects: the vivisection debate in German and British
      medical weekly journals 1919-1939].
AB  - By the end of the 1920s, animal experiments were considered a standardized
      procedure for testing medical substances and therapies. In the context of the so
      called "crisis of medicine", however, some physicians and the wider lay public in
      Germany and Great Britain criticized animal based research. While British
      antivivisectionists had little relevance in the 1930s, their German counterparts
      allied with the National Socialist Party and gained social and political force.
      The debates within the German and British medical profession about doctors'
      interventions in that debate, as well as the public perception of doctors will be
      analysed on the basis of the most important medical weekly journals of the time,
      that were involved in these debates.

PMID- 19746884
TI  - [Occupational diseases in Poland, 2008].
AB  - BACKGROUND: The aim of the paper was to present basic statistical data on
      occupational diseases diagnosed in 2008. MATERIAL AND METHODS: The work was based
      on the data compiled from "Occupational Disease Reporting Forms" received by the
      Central Register of Occupational Diseases in 2008. The data comprised information
      on nosologic units, gender and age of patients, and duration of occupational
      exposure to harmful agents responsible for the development of specified
      pathologies. These data were further classified by sectors of the national
      economy and voivodeships. The incidence was specified in terms of the number of
      cases in relation to paid employees or to employed persons. RESULTS: The number
      of occupational diseases diagnosed in 2008 accounted for 3546 cases. The
      incidence rate was 34.7 cases per 100,000 paid employees. The highest incidence
      rates were noted for infectious and parasitic diseases (9.4/100,000), chronic
      voice disorders (7.9) and pneumoconioses (6.8). As many as 77.9% of patients
      affected by occupational diseases had been exposed to harmful agents for longer
      than 20 years. In industrial sectors of the national economy, the highest
      incidence rate was noted in the coal mining industry (416.3 cases per 100,000).
      The highest incidence rates were recorded in the Lubelskie (75.5), Silesian
      (66.3) and Podlaskie (60.7) voivodeships. CONCLUSIONS: An increase of 261 (7.9%)
      cases of occupational diseases and an increase of 3.6% in their incidence rate
      over the previous year were noted in 2008. The greatest increase was noted in
      infectious and parasitic diseases (of 285 cases, i.e. 42.5%) and chronic diseases
      of the locomotor system (of 22 cases i.e. 22.4%).

PMID- 19746885
TI  - [Occupational exposure limits for polycyclic aromatic hydrocarbons. Current legal
      status and proposed changes].
AB  - BACKGROUND: The evaluation of occupational exposure to polycyclic aromatic
      hydrocarbons (PAHs) in Poland is based on the results of measurements of their
      concentrations in workplace air compared to appropriate occupational exposure
      limits. The inconsistence in current regulations is the source of many
      interpretation-related problems. OBJECTIVE: The objective of this work was to
      determine PAH concentrations in different technological processes and to analyze
      statistically the obtained data to indicate the presence (or absence) of
      differences between exposure indices calculated for 9 PAHs listed in the decree
      of the Minister of Labor and those (8 compounds) set by the Minister of Health.
      MATERIALS AND METHODS: Air samples were collected during graphite electrode
      production, coke production, aluminum smelting, tire production and road paving.
      PAH concentrations in collected air samples were analyzed by HPLC. RESULTS: The
      obtained data calculated for each technological process indicate that indices of
      exposure based on 8 or 9 PAHs, taking into account their relative
      carcinogenicity, did not differ considerably and are not statistically different
      from exposure indices calculated for 11 PAHs. CONCLUSIONS: In view that the
      indices of exposure calculated for 8 and 9 compounds are not statistically
      different and that of all the PAHs listed in the decree of the Minister of Labor,
      two compounds are not classified as carcinogenic, it seems justified to
      substitute the latter by the list of compounds issued by the Minister of Health.
      The proposed modification should result in a better consistency of legal
      regulations without altering the quality of the occupational exposure evaluation.
      Furthermore, removing benzo(a)pyrene and dibenzo(ah)anthracene from the OEL list
      should solve the existing interpretation-related problems.

PMID- 19746886
TI  - [Musculoskeletal system load in operating room nurses and its determinants].
AB  - BACKGROUND: The aims of the survey was to analyze the musculoskeletal system load
      during work performed by operating room nurses, and to identify the most loading
      activities along with their causes. MATERIAL AND METHODS: The observation of work
      process and the Ovako Working posture Analysing System (OWAS) method for
      analyzing and evaluating work postures were used as major tools of this survey.
      Altogether 170 observations of work process were made and also seven basic work
      activities and 101,320 work postures were selected. RESULTS AND CONCLUSIONS: The
      results of the survey show: a) average proportion of time spent by nurses on
      individual tasks during the shift were: preparation for operative procedure--16%,
      instrumentation nurse tasks--16%, circulating nurse tasks--13%, cleaning after
      operative procedure--4%, cleaning and preparation of surgical instruments--4%,
      breaks at work--43% and other tasks--4%; b) average proportion of time spent by
      nurses in OWAS posture categories were: category 1--89%, category 2--10%,
      category 3 and 4--1%. The collected data revealed that the main causes of the
      musculoskeletal system load in all tasks were: time spent by nurses on awkward
      postures during the shift (inability to change postures), awkward postures with a
      hard load (manual lifting or transporting the equipment, more than 10 kg and also
      above 20 kg). It should be emphasized that the identified causes of loading
      activities resulted from poor work organization and technical working conditions.

PMID- 19746887
TI  - [Global Adult Tobacco Survey in Poland--the aim and current experiences].
AB  - Poland is one of the countries, where smoking is widely spread and smoking
      induced diseases have become a significant health and socio-economic issue. Since
      1999, the World Health Organization (WHO) and Centers for Disease Control and
      Prevention (CDC), in cooperation with partner organizations have been working on
      the implementation of the global control system known as the Global Tobacco
      Surveillance System (GTSS). This system expands the opportunities of individual
      countries in the area of designing, implementing and evaluating comprehensive
      anti-tobacco programs. The Global Adult Tobacco Survey (GATS) has been
      incorporated into the GTSS system in 2007. The aim of the work is to explain and
      promote the objectives of GATS and the process of its implementation in Poland
      based on current experiences of the WHO Country Office for Poland. GATS
      concentrates on monitoring of tobacco use by adults (aged over 15 years). It is a
      representative, national survey of households, standardized on a global scale.
      GATS is supported by Bloomberg Philanthropies as a part of the Bloomberg Global
      Initiative to Reduce Tobacco Use. Two executive agencies, the M. Sklodowska-Curie
      Institute of Oncology, Warsaw and the Warsaw Medical University, have been
      assigned to implement the Global Adult Tobacco Survey in Poland. The prepatory
      works for pre-testing and further stages of the survey implementation are
      currently under the final phase. Data gathered by GATS will enable us to learn
      more about the use of tobacco by the adult population in Poland. They will also
      indicate the most effective methods of the tobacco control in our country.

PMID- 19746888
TI  - [Welding-related respiratory diseases].
AB  - Welders are exposed to fumes containing different gases, fumes and particles,
      depending on the composition of the welding electrodes, welded material and the
      welding method used. Welders are workers at risk of developing various
      respiratory signs and symptoms. Health effects associated with welding include
      different lung function abnormalities, including metal fume fever, bronchial
      asthma, chronic obstructive pulmonary disease, pneumoconiosis and other pulmonary
      fibrosis (chronic beryllium disease, cobalt lung), and lung cancer. The authors
      describe some aspects of etiology, pathogenesis, diagnostics, prophylaxis, and
      medical certification of welding-related respiratory diseases.

PMID- 19746889
TI  - [Irritant contact dermatitis. Part II. Evaluation evaluation of skin irritation
      potential of chemicals].
AB  - The evaluation of skin irritation potential of chemicals is essential to secure
      the safety of individuals exposed to several substances designed for industrial,
      pharmaceutical or cosmetic use. Until recently, preclinical safety assessment of
      chemicals was largely based on animal experiments. Ethical concerns and the
      limited value of animal models in evaluating human skin irritation potential
      resulted in the development of alternative in vitro methods, such as EpiDerm,
      EPISKIN or SkinEthic, to assess irritation, i.e. cell cultures and human
      epidermis models. International organizations like the European Centre for the
      Validation of Alternative Methods (ECVAM) promotes and monitors the development
      of nonanimal tests. Human patch tests and use tests also provide an opportunity
      to identify substances with significant skin irritation potential without
      recourse to the use of animals. These tests are useful to assess skin irritation
      potential of cosmetics and detergents.

PMID- 19746890
TI  - [Quantitative methods of cancer risk assessment in exposure to chemicals].
AB  - This is a methodology paper--it contains a review of different quantitative risk
      assessment methods and their comparison. There are two aspects of cancer risk
      modeling discussed here: 1. When there is one effective dose only. There were
      compared two models in this evaluation: one proposed by the Dutch Expert
      Committee on Occupational Standards and the other--a classical two-stage model.
      It was taken into account that in both models the animals were exposed for less
      than two years. An exposure period and a study period of animals were considered
      in the Dutch methodology. If we use as an exposure measure average lifespan dose
      estimated with different coefficients of exposure time in an experiment, we get
      two different dose-response models. And each of them will create different human
      risk models. There is no criterion that would let us assess which of them is
      better. 2. There are many models used in the BenchMark Dose (BMD) method. But
      there is no criterion that allows us to choose the best model objectively. In
      this paper a two-stage classical model and three BMD models (two-stage, Weibull
      and linear) were fit for particular data. Very small differences between all the
      models were noticed. The differences were insignificant because of uncertainties
      in the risk modeling. The possibility of choice of one model from a bigger set of
      models is the greatest benefit of this comparison. If the examined chemical is a
      genotoxic carcinogen, nothing more is needed than to estimate the threshold
      value.

PMID- 19746891
TI  - [Risk of neoplastic diseases in conditions of exposure to power magnetic fields-
      epidemiologic investigations].
AB  - The review paper presents current views on risks of incidence of neoplasms in
      persons exposed to power magnetic fields (PMFs) 50 Hz in the environment or at
      working posts. Cancer risks of power magnetic fields are small and doubtful, but
      there exist confirmed epidemiologic investigations that in children living in
      homes where PMF intensity exceeds 0.3-0.4 microT (0.24-0.32 A/m) an increased
      risk of certain types of leukemias can be observed. About one percent of children
      live under conditions of PMF exposure. Cancer morbidity in workers exposed to
      power magnetic fields is not unequivocally increased. Ten years ago, on the basis
      of available epidemiologic data, PMFs 50 Hz were listed as a possible
      carcinogenic agent (group 2B according to the IARC classification), which means
      lack of convincing evidence that PMFs pose cancer risks. The authors also discuss
      the binding regulations on the protection of the general population and workers
      against power magnetic fields and they conclude that existing permissible
      exposure levels are incompatible with exposure conditions, the present state of
      knowledge and health threats.

PMID- 19746892
TI  - [Electromagnetic fields hypersensitivity].
AB  - The development of industry, particularly of new technologies in communication
      systems, gives rise to the number and diversty of electromagnetic field (EMF)
      sources in the environment. These sources, including power-frequent,
      radiofrequent and microwaves, make human life richer, safer and easier. But at
      the same time, there is growing concern about possible health risks connected
      with EMF exposure. An increasing number of persons have recently reported on a
      variety of health problems induced, in their opinion, by exposure to EMF. It is
      important to note that EMF levels to which these individuals are exposed are
      generally well below the recommended exposure limits and are certainly far below
      those known to produce any adverse effects. These persons call themselves
      "electromagnetic hypersensitivity individuals" And complain about experiencing
      various types of non-specific symptoms, including dermatological, neurological
      and vegetative. In the present paper, the problem of electromagnetic
      hypersensitivity phenomenon is discussed based on the recently published
      literature.

PMID- 19746893
TI  - Theoretical study on the f-f transition intensities of lanthanide trihalide
      systems.
AB  - The photoabsorption intensities of intra-4f(N) transitions (f-f transitions) in
      lanthanide systems have been extensively studied with the semiempirical Judd
      Ofelt theory. The oscillator strengths of most f-f transitions are insensitive to
      a change of surrounding environment because 4f electrons are shielded by closed
      shell 5s and 5p electrons from outside. However, there are some exceptional
      transitions, so-called hypersensitive transitions, whose intensities are very
      sensitive to a change of surrounding environment, and the reason for this
      hypersensitivity has not been clarified. In this study, we calculated the
      oscillator strengths of lanthanide trihalides (LnX(3); Ln = Pr, Tm; X = Br, I)
      with the multireference spin-orbit configuration interaction method and obtained
      reasonably accurate values. To clarify the cause of hypersensitivity, we examined
      various possible effects on the oscillator strengths, such as molecular
      vibration, f-d mixing, ligand to metal charge transfer (LMCT), and intraligand
      excitation, and concluded that the effect of molecular vibration is very small
      and that the oscillator strengths of most f-f transitions including
      hypersensitive transitions arise from both the LMCT and dynamic-coupled
      intraligand excitations through their configuration mixings with the dominant
      configurations of 4f(N).

PMID- 19746894
TI  - pi-Delocalization in oligoalkynes induced by push-pull substituents and 1,3
      conjugation: a combined (13)C NMR and computational study.
AB  - (13)C chemical shifts of the push-pull oligoalkynes Don-(C identical withC)(n)
      Acc (n = 1-4; Don = morpholino; Acc = COMe, COOMe) were computed at the DFT
      (B3LYP/6-311+G(d,p) level of theory compared with the experimental delta values
      and the agreement employed as a measure of quality for the underlying structures.
      For the global minima structures, the occupation quotients of antibonding pi* and
      bonding pi orbitals (pi*(C[triple bond]C)/pi(C[triple bond]C)) and the bond
      lengths (d(C[triple bond]C)) of the various C[triple bond]C triple bonds were
      also computed and correlated to each other. The linear dependence obtained for
      the two parameters d(C identical withC) and pi*(C[triple bond]C)/pi(C[triple
      bond]C) quantifies changes in pi-delocalization induced by the push-pull effect
      of the substituents and 1,3-conjugation (1,3,5- and 1,3,5,7-, respectively) of
      the C identical withC bonds in the oligoalkynes studied. A critical comparison of
      the push-pull effect, attenuated with increasing n, and the conjugative
      stabilization of the oligoalkynes, increasing with n, as concluded from d(C
      identical withC) and pi*(C[triple bond]C)/pi(C[triple bond]C) of the oligoalkynes
      and the reference compounds Me-(C[triple bond]C)(n)-Me, Don-(C[triple bond]C)(n)
      Me, and Me-(C[triple bond]C)(n)-Acc), respectively (Don = morpholino; Acc = COMe,
      COOMe), is affiliated.

PMID- 19746895
TI  - Heat of formation of the allyl ion by TPEPICO spectroscopy.
AB  - The 0 K onset of C(3)H(6) --> C(3)H(5)(+) + H(*) is measured by threshold
      photoelectron-photoion coincidence (TPEPICO) spectroscopy. From the onset (11.898
      +/- 0.025 eV) the heat of formation of the allyl ion (CH(2)CHCH(2)(+)) is
      determined to be DeltaH degrees (f,0K) = 967.2; DeltaH degrees (f,298K) = 955.4
      +/- 2.5 kJ mol(-1). The value is significantly more positive than prior
      determinations, and resolves a discrepancy between measurements of the allyl
      radical and allyl ion heats of formation and recent highly precise measurements
      of the allyl radical adiabatic ionization energy. The new allyl ion heat of
      formation leads to a new proton affinity for propadiene (allene) of 765.0 +/- 2.6
      kJ mol(-1). An attempt is made to determine the CH(3)CCH(2)(+) heat of formation
      by measuring the 0 K onset of 2-ClC(3)H(5) --> C(3)H(5)(+) + Cl(*). However,
      C(3)H(5)(+) appears at too low an energy to be the higher energy CH(3)CCH(2)(+)
      structure. Rather, 2-ClC(3)H(5)(+) undergoes a concerted hydrogen transfer and Cl
      loss via an intramolecular S(N)2 like mechanism to produce the allyl ion. The 0 K
      onset of 3-ClC(3)H(5) --> C(3)H(5)(+) + Cl(*) (11.108 +/- 0.010 eV) is measured
      to determine the 3-ClC(3)H(5) heat of formation (DeltaH degrees (f,0K) = 14.9;
      DeltaH degrees (f,298K) = 1.1 +/- 2.7 kJ mol(-1)). 3-ClC(3)H(5)(+) is suggested
      to readily isomerize to trans 1-ClC(3)H(5)(+) prior to dissociation.

PMID- 19746896
TI  - Homo- and heterometallic complexes of tetra-(di-substituted hydroxybenzyl)-N,N'
      ethylenediamine derivatives.
AB  - The coordination behavior of a series of group 4 metal alkoxides [M(OR)(4)]
      modified by a set of novel substituted hydroxybenzyl ethylene diamine (H(4)-ED
      L(4)) ligands {[tetra(3,5-di-t-butyl-2-hydroxybenzyl)-N,N'-ethylenediamine]
      termed H(4)-ED-DBP(4) (1), [tetra(3,5-di-t-amyl-2-hydroxybenzyl)-N,N'
      ethylenediamine] termed H(4)-ED-DAP(4) (1a), and [tetra(3,5-dichloro-2
      hydroxybenzyl)-N,N'-ethylenediamine] termed H(4)-ED-DCP(4) (2)} was elucidated.
      The reaction of 1 or 1a with the M(OR)(4) precursor led to the isolation of the
      structural similar species M(ED-L(4)) where L = DBP, M = Ti (3), Zr (4), Hf (5);
      L = DAP, M = Zr (4a), Hf (5a). In contrast, the reaction of 2 with the M(OR)(4)
      precursors yielded Ti(ED-DCP(4)) (6), (py)(2)Zr(ED-DCP(4)) (7), and
      (HOBu(t))Hf(ED-DCP(4)) (8) where py = pyridine and HOBu(t) = HOC(CH(3))(3). For 3
      6, the cations of the monomeric species were completely encapsulated by all
      available heteroatoms (four O and two N) of the ED-L(4) ligands, yielding an
      octahedral geometry for each metal center. For 7 and 8, an identical binding by
      the ED-DCP(4) ligand was observed with the additional coordination of Lewis basic
      adducts, forming 8- and 7-coordinated metal centers, respectively. Switching to
      +2 cations led to the isolation of [(THF)Ca](2)(ED-DBP(4)) (9a) where THF =
      tetrahydrofuran, {[(py)Ca](4)(ED-(mu-DBP-eta(6))(4))(2)}(n) (9b), and [(py)Zn](ED
      DBP(4))[Zn(py)(2)] (10) *5py and [(py)Sn](2)(ED-DBP(4)) (11). The structures of
      these species were significantly different in arrangement compared to the Group 4
      derivatives. Further attempts to produce a mixed +4/+2 cationic species yielded
      [(py)(ONep)(2)Ti(ED-DBP(4))Zn(py)] (12). Reacting the single-source precursor
      Co[mu-OC(6)H(4)(CHMe(2))(2)-2)(2)Li(py)(2)](2) with 1, led to the isolation of
      (py)Li[ED-DBP(3)(H-DBP)]Co (13), with one of the phenol protons remaining
      unreacted. The synthesis and characterization of these compounds are presented in
      detail.

PMID- 19746897
TI  - Electrochemically-induced TCNQ/Mn[TCNQ]2(H2O)2 (TCNQ = 7,7,8,8
      tetracyanoquinodimethane) solid-solid interconversion: two voltammetrically
      distinct processes that allow selective generation of nanofiber or nanorod
      network morphologies.
AB  - Unlike the case with other divalent transition metal M[TCNQ](2)(H(2)O)(2) (M =
      Fe, Co, Ni) analogues, the electrochemically induced solid-solid phase
      interconversion of TCNQ microcrystals (TCNQ = 7,7,8,8-tetracyanoquinodimethane)
      to Mn[TCNQ](2)(H(2)O)(2) occurs via two voltammetrically distinct, time dependent
      processes that generate the coordination polymer in nanofiber or rod-like
      morphologies. Careful manipulation of the voltammetric scan rate, electrolysis
      time, Mn(2+)((aq)) concentration, and the method of electrode modification with
      solid TCNQ allows selective generation of either morphology. Detailed ex situ
      spectroscopic (IR, Raman), scanning electron microscopy (SEM), and X-ray powder
      diffraction (XRD) characterization clearly establish that differences in the
      electrochemically synthesized Mn-TCNQ material are confined to morphology.
      Generation of the nanofiber form is proposed to take place rapidly via formation
      and reduction of a Mn-stabilized anionic dimer intermediate, [(Mn(2+))(TCNQ
      TCNQ)(2)(*-)], formed as a result of radical-substrate coupling between TCNQ(*-)
      and neutral TCNQ, accompanied by ingress of Mn(2+) ions from the aqueous solution
      at the triple phase TCNQ/electrode/electrolyte boundary. In contrast, formation
      of the nanorod form is much slower and is postulated to arise from
      disproportionation of the [(Mn(2+))(TCNQ-TCNQ)(*-)(2)] intermediate. Thus,
      identification of the time dependent pathways via the solid-solid state
      electrochemical approach allows the crystal size of the Mn[TCNQ](2)(H(2)O)(2)
      material to be tuned and provides new mechanistic insights into the formation of
      different morphologies.

PMID- 19746898
TI  - Synthesis and coordination properties of quinoline pendant arm derivatives of
      [9]aneN(3) and [9]aneN(2)S as fluorescent zinc sensors.
AB  - The coordination chemistry of three new quinoline pendant arm derivatives of
      [9]aneN(3) (L(1), L(2)) and [9]aneN(2)S (L(3)) toward Cu(II), Zn(II), Cd(II),
      Hg(II), and Pb(II) has been investigated both in solution and in the solid state.
      The protonation constants for L(1)-L(3) and stability constants with the
      aforementioned metal ions have been determined potentiometrically in 0.10 M
      NMe(4)Cl MeCN/H(2)O (1:1 v/v) solution at 298.1 +/- 0.1 K; the measured values
      show that Cu(II) has the highest affinity for all three ligands, followed by
      Zn(II), Hg(II), Pb(II), and Cd(II). For each metal ion considered, 1:1 complexes
      with L(1)-L(3) have also been isolated in the solid state and
      [Cu(L(1))](BF(4))(2) (1), [Zn(L(1))](BF(4))(2) (2), [Cd(L(1))](ClO(4))(2) (3),
      [Hg(L(1))](NO(3))(2) (4), [Pb(L(1))](ClO(4))(2) x MeCN (5),
      [Zn(2)Cl(2)(L(2))(2)](BF(4))(2) x 1/2 MeNO(2) x H(2)O (6), [Cu(L(3))](ClO(4))(2)
      (7), [Zn(L(3))(NO(3))]NO(3) (8), [Cd(L(3))(NO(3))(0.82)Cl(0.18)]NO(3) (9), and
      [Hg(L(3))](ClO(4))(2) x MeCN (10) have also been characterized by X-ray
      crystallography. The optical response of L(1)-L(3) to the presence of the above
      mentioned metal ions has been investigated in MeCN/H(2)O (1:1 v/v) and H(2)O
      solutions. All three ligands show a stronger "OFF-ON" CHEF (chelation enhancement
      of fluorescence) effect in the Zn(II) complexes than in the Cd(II) complexes in
      both media. The results have been examined by considering the ratio
      I(rel)(Zn(II))/I(rel)(Cd(II)), within the emerging idea that the relative
      strength of the CHEF effect for the small Zn(II) ion as compared to larger Cd(II)
      ion might be determined by steric crowding in the corresponding complexes with
      quinoline-based fluorescent chemosensors.

PMID- 19746899
TI  - Rechargeable batteries driven by redox reactions of Mn12 clusters with structural
      changes: XAFS analyses of the charging/discharging processes in molecular cluster
      batteries.
AB  - Molecular clusters such as the Mn12 cluster (Mn12) can be used as a cathode
      active material in Li batteries. X-ray absorption fine structure studies on the
      cathode materials in Mn12 molecular cluster batteries demonstrated that the
      charging/discharging processes include four-electron-redox reaction of Mn12 with
      a significant change in its molecular structure.

PMID- 19746900
TI  - Chromium acetylide complex based ferrimagnet and weak ferromagnet.
AB  - The crystal structures and magnetic properties of new molecule-based magnets,
      [CrCyclam(C[triple bond]C-3-thiophene)(2)][Ni(mdt)(2)] (1) and [CrCyclam(C[triple
      bond]C-Ph)(2)][Ni(mdt)(2)](H(2)O) (2) (Cyclam = 1,4,8,11
      tetraazacyclotetradecane, mdt = 1,3-dithiole-4,5-dithiolate), are reported. The
      crystal structures of both compounds are characterized by ferrimagnetic chains of
      alternately stacked [CrCyclam(C[triple bond]C-R)](+) cations and [Ni(mdt)(2)](-)
      anions with intrachain exchange interactions of 2J = -6.1 K in 1 and -5.7 K in 2
      (H = -2J Sigma(i) S(i) x S(i+1)). The material 1 exhibits ferrimagnetic
      transition at 2.3 K owing to weak interchain antiferromagnetic interactions
      between cations and anions. In the case of 2, cations in adjacent ferrimagnetic
      chains are bridged by a water molecule, resulting in an interchain
      antiferromagnetic coupling. Despite a centrosymmetry of a whole crystal of 2, one
      bridging water molecule occupies only one of the two centrosymmetric sites and
      breaks a local centrosymmetry between adjacent cations. The interchain
      antiferromagnetic interaction and Dzyaloshinsky-Moriya interaction originated
      from the local symmetry breakdown of 2 bring a weak-ferromagnetic transition at
      3.7 K with a coercive force of less than 0.8 mT, followed by the second magnetic
      phase transition at 2.9 K. Below this temperature, the coercive force rapidly
      increases from 1 to 11.8 mT as the temperature decreases from 2.9 to 1.8 K, while
      the remanent magnetization monotonically increases from 0.008 mu(B) at 3.6 K to
      0.12 mu(B) at 1.8 K.

PMID- 19746901
TI  - Sodium and potassium ion directed self-assembled multinuclear assembly of
      divalent nickel or copper and L-leucine derived ligand.
AB  - L-leucine derived ligand (H(2)L(L-leu)), KOH, and Ni(II) salt in 2:2:1 ratio self
      assembled into a rather large (approximately 13 A) supramolecular assembly with
      the formula [K{Ni(HL(L-leu))(2)}(3)](+) (1). Structural characterization showed
      three [Ni(HL(L-leu))(2)] units encapsulated K(+) similar to organic crown
      ethers/cryptand. Substituting Ni(II) with Cu(II) and K(+) with Na(+) in the above
      reaction resulted in a set of structurally identical assemblies with the general
      formula [M'{M(HL(L-leu))(2)}(3)](+), where M' is either K(+) or Na(+) and M is
      either Cu(II) or Ni(II); [Na{Ni(HL(L-leu))(2)}(3)]ClO(4) (2), Na{Ni(HL(L
      leu))(2)}(3)]OTf (3), [K{Cu(HL(L-leu))(2)}(3)]ClO(4) (4), [Na{Cu(HL(L
      leu))(2)}(3)]ClO(4) (5), [K{Cu(HL(L-leu))(2)}(3)]NO(3) (6). Electrospray
      Ionization (ESI)-mass spectra of the assemblies in MeOH showed the retention of
      assemblies in solution. Visible spectroscopic studies showed retention of
      assembly 1 in N,N-dimethylformamide (DMF) which is stable even after the addition
      of 5 equiv of [18]-crown-6. The assemblies in 2-6 show various degrees of
      dissociation to [M(HL(L-leu))(2)] and M', in stronger H-bonding methanol. The
      dissociation can be reversed upon addition of excess KNO(3)/NaNO(3) salt.
      Structural characterization of [Cu(HL(L-leu))(2)(MeCN)] (7) along with its
      transformation to [K{Cu(HL(L-leu))(2)}(3)](+) in the presence of K(+) salt
      demonstrated that the assembly formation proceeds through an alkali metal ion
      induced ligand reorientation within the [Cu(HL(L-leu))(2)] units which is further
      stabilized by six strong H-bonds holding the assembly. Interestingly, visible
      spectra of 1 and 2 shows that minor structural changes caused by replacing K(+)
      with Na(+) is sufficient to shift the d-d transition of Ni(II) by approximately
      70 nm, thereby providing an indirect way of distinguishing K(+) and Na(+), none
      of which have spectroscopic signature in the visible range.

PMID- 19746902
TI  - Relative binding affinity of thiolate, imidazolate, phenoxide, and nitrite toward
      the {Fe(NO)2} motif of dinitrosyl iron complexes (DNICs): the characteristic pre
      edge energy of {Fe(NO)2}9 DNICs.
AB  - The synthesis, characterization, and transformation of the anionic {Fe(NO)(2)}(9)
      dinitrosyl iron complexes (DNICs) [(NO)(2)Fe(ONO)(2)](-) (1),
      [(NO)(2)Fe(OPh)(2)](-) (2), [(NO)(2)Fe(OPh)(C(3)H(3)N(2))](-) (3) (C(3)H(3)N(2) =
      imidazolate), [(NO)(2)Fe(OPh)(-SC(4)H(3)S)](-) (4), [(NO)(2)Fe(p-OPhF)(2)](-)
      (5), and [(NO)(2)Fe(SPh)(ONO)](-) (6) were investigated. The binding affinity of
      ligands ([SPh](-), [-SC(4)H(3)S](-), [C(3)H(3)N(2)](-), [OPh](-), and [NO(2)](-))
      toward the {Fe(NO)(2)}(9) motif follows the ligand-displacement series [SPh](-)
      approximately [-SC(4)H(3)S](-) > [C(3)H(3)N(2)](-) > [OPh](-) > [NO(2)](-). The
      findings, the pre-edge energy derived from the 1s --> 3d transition in a
      distorted T(d) environment of the Fe center falling within the range of 7113.4
      7113.8 eV for the anionic {Fe(NO)(2)}(9) DNICs, implicate that the iron metal
      center of DNICs is tailored to minimize the electronic changes accompanying
      changes in coordinated ligands. Our results bridging the ligand-substitution
      reaction study and X-ray absorption spectroscopy study of the electronic richness
      of the {Fe(NO)(2)}(9) core may point the way to understanding the reasons for
      nature's choice of combinations of cysteine, histidine, and tyrosine in protein
      bound DNICs and rationalize that most DNICs characterized/proposed nowadays are
      bound to the proteins almost through the thiolate groups of
      cysteinate/glutathione side chains in biological systems.

PMID- 19746903
TI  - Low-temperature N-O bond cleavage in nitrosyl ligands induced by the unsaturated
      dimolybdenum anion [Mo2(eta(5)-C5H5)2(mu-PPh2)(mu-CO)2]-.
AB  - The unsaturated anion [Mo(2)Cp(2)(mu-PPh(2))(mu-CO)(2)](-) (1) (Na(+) salt)
      reacts with the nitrosyl complexes [MCp'(CO)(2)(NO)]BF(4) (M = Mn, Re; Cp' =
      eta(5)-C(5)H(4)Me) rapidly at about 193 K. Upon warming of the resulting mixtures
      up to 243 K orange solutions are obtained, shown to contain the corresponding oxo
      and nitride-bridged tetracarbonyl complexes [Mo(2)MCp(2)Cp'(mu-N)(mu-O)(mu
      PPh(2))(CO)(4)] as the major product, which could be isolated only for M = Re.
      Above 253 K, however, these compounds experience spontaneous decarbonylation to
      yield the unsaturated tricarbonyl derivatives [Mo(2)MCp(2)Cp'(mu-N)(mu-O)(mu
      PPh(2))(CO)(3)] (Mo-Mo = 2.840 A for the Mn compound, according to density
      functional theory (DFT) calculations). These complexes in turn react rapidly with
      air to give the corresponding dioxodicarbonyl derivatives [Mo(2)MCp(2)Cp'(mu
      N)(mu-O)(mu-PPh(2))(O)(CO)(2)] almost quantitatively. The structure of the latter
      product (M = Re) was determined by X-ray diffraction methods (Mo-Mo = 2.763(1)
      A). In contrast with the N-O bond cleavage easily taking place in the above
      reactions, the direct nitrosylation of 1 with N-methyl-N-nitroso-p
      toluenesulfonamide induces no bond cleavage process in the nitrosyl ligand, but
      just gives the electron-precise tricarbonyl derivative [Mo(2)Cp(2)(mu
      PPh(2))(CO)(3)(NO)] or, in the presence of CN(t)Bu, a mixture of the new
      isocyanide complexes [Mo(2)Cp(2)(mu-PPh(2))(CN(t)Bu)(CO)(2)(NO)] and
      [Mo(2)Cp(2)(mu-PPh(2))(mu-eta(1):eta(2)-CN(t)Bu)(CO)(NO)]. Separate experiments
      indicated that these isocyanide complexes cannot be converted one into each
      other, nor can they be obtained through thermal substitution reactions on the
      above tricarbonyl product.

PMID- 19746904
TI  - Low temperature 65Cu NMR spectroscopy of the Cu+ site in azurin.
AB  - (65)Cu central-transition NMR spectroscopy of the blue copper protein azurin in
      the reduced Cu(I) state, conducted at 18.8 T and 10 K, gave a strongly second
      order quadrupole perturbed spectrum, which yielded a (65)Cu quadrupole coupling
      constant of +/-71.2 +/- 1 MHz, corresponding to an electric field gradient of +/
      1.49 atomic units at the copper site, and an asymmetry parameter of approximately
      0.2. Quantum chemical calculations employing second order Moller-Plesset
      perturbation theory and large basis sets successfully reproduced these
      experimental results. Sensitivity and relaxation times were quite favorable,
      suggesting that NMR may be a useful probe of the electronic state of copper sites
      in proteins.

PMID- 19746905
TI  - Frustration of magnetic and ferroelectric long-range order in
      Bi(2)Mn(4/3)Ni(2/3)O(6).
AB  - The slight incommensurate modulation of the structure of Bi(2)Mn(4/3)Ni(2/3)O(6)
      is sufficient to suppress the electrical polarization which arises in
      commensurate treatments of the structure, due to antiferroelectric coupling of
      local polar units of over 900 A(3). The incommensurate structure is produced by
      the competition between ferroelectric Bi lone pair-driven A site displacement,
      chemical order of Mn and Ni on the B site, and both charge and orbital order at
      these transition metals. The interplay between the frustrated polar Bi
      displacements and the frustrated spin order at the B site, induced by positional
      disorder, produces magnetodielectric coupling between the incommensurately
      modulated lattice and the spin-glass-like ground state with an unusual
      relationship between the magnetocapacitance and the applied field.

PMID- 19746906
TI  - Domain insertion effectively regulates the mechanical unfolding hierarchy of
      elastomeric proteins: toward engineering multifunctional elastomeric proteins.
AB  - The architecture of elastomeric proteins controls fine-tuned nanomechanical
      properties of this class of proteins. Most elastomeric proteins are tandem
      modular in structure, consisting of many individually folded domains of varying
      stability. Upon stretching, these elements unfold sequentially following a strict
      hierarchical pattern determined by their mechanical stability, where the weakest
      element unfolds first and the strongest unfolds last. Although such a
      hierarchical architecture is well-suited for biological functions of elastomeric
      proteins, it may become incompatible with incorporating proteins of desirable
      functionality in order to construct multifunctional artificial elastomeric
      proteins, as many of these desired proteins are not evolved for mechanical
      purpose. Thus, exposure to a high stretching force will result in unraveling of
      these proteins and lead to a loss of their functionality. To overcome this
      challenge, we combine protein engineering with single molecule force spectroscopy
      to demonstrate that domain insertion is an effective strategy to control the
      mechanical unfolding hierarchy of multidomain proteins and effectively protect
      mechanically labile domains. As a proof-of-principle experiment, we spliced a
      mechanically labile T4 lysozyme (T4L) into a flexible loop of a mechanically
      stronger host domain GL5 to create a domain insertion protein. Using single
      molecule force spectroscopy, we showed that the mechanically labile T4L domain
      unfolds only after the mechanically stronger host domain GL5 has unfolded. Such a
      reverse mechanical unfolding hierarchy effectively protects the mechanically
      labile T4L domain from applied stretching force and significantly increased the
      lifetime of T4L. The approach demonstrated here opens the possibility to
      incorporate labile proteins into elastomeric proteins for engineering novel
      multifunctional elastomeric proteins.

PMID- 19746909
TI  - Subtle balance of ligand steric effects in Stille transmetalation.
AB  - Experimental results have previously suggested that the transmetalation step in
      the Stille reaction is hindered at one extreme by very bulky ligands L on the
      PdL(2) catalyst, yet at the other extreme, transmetalation is also found to be
      slow for small ligands. Our aim in this paper is to resolve this dilemma using
      computational chemistry and to show which ligand is best and why. With the use of
      density functional theory we show that the reason why L = P(t)Bu(3) retards
      transmetalation is because the bulky ligand hinders the coordination of the
      organostannane. On the other hand a small ligand such as L = PMe(3) leads to the
      formation of a very stable intermediate in the catalytic cycle which then
      requires a large activation energy for the transmetalation to proceed. The L =
      PPh(3) ligand appears to provide just the right balance in that it can readily
      coordinate the organostannane but avoids forming the very stable intermediate,
      and is thus the ligand of choice. L = PPh(2)Me is predicted to be the next best
      option, but L = PPhMe(2) is too small and forms an intermediate whose stability
      prevents further reaction in the transmetalation step. Our calculations are also
      able to account for the accelerating role of CsF in the transmetalation step of
      the Stille reaction. Finally, this work demonstrates the importance of taking
      into account the steric properties of the full ligand in theoretical studies of
      such reactions, rather than using small model phosphines.

PMID- 19746908
TI  - Biologically functional cationic phospholipid-gold nanoplasmonic carriers of RNA.
AB  - Biologically functional cationic phospholipid-gold nanoplasmonic carriers have
      been designed to simultaneously exhibit carrier capabilities, demonstrate
      improved colloidal stability, and show no cytotoxicity under physiological
      conditions. Cargo, such as RNA, DNA, proteins, or drugs, can be adsorbed onto or
      incorporated into the cationic phospholipid bilayer membrane. These carriers are
      able to retain their unique nanoscale optical properties under physiological
      conditions, making them particularly useful in a wide range of imaging,
      therapeutic, and gene delivery applications that utilize selective nanoplasmonic
      properties.

PMID- 19746907
TI  - Characterization and mechanistic studies of DesII: a radical S-adenosyl-L
      methionine enzyme involved in the biosynthesis of TDP-D-desosamine.
AB  - D-desosamine (1) is a 3-(N,N-dimethylamino)-3,4,6-trideoxyhexose found in a
      number of macrolide antibiotics including methymycin (2), neomethymycin (3),
      pikromycin (4), and narbomycin (5) produced by Streptomyces venezuelae . It plays
      an essential role in conferring biological activities to its parent aglycones.
      Previous genetic and biochemical studies of the biosynthesis of desosamine in S.
      venezuelae showed that the conversion of TDP-4-amino-4,6-dideoxy-D-glucose (8) to
      TDP-3-keto-4,6-dideoxy-D-glucose (9) is catalyzed by DesII, which is a member of
      the radical S-adenosyl-L-methionine (SAM) enzyme superfamily. Here, we report the
      purification and reconstitution of His(6)-tagged DesII, characterization of its
      [4Fe-4S] cluster using UV-vis and EPR spectroscopies, and the capability of
      flavodoxin, flavodoxin reductase, and NADPH to reduce the [4Fe-4S](2+) cluster.
      Also included are a steady-state kinetic analysis of DesII-catalyzed reaction and
      an investigation of the substrate flexibility of DesII. Studies of deuterium
      incorporation into SAM using TDP-[3-(2)H]-4-amino-4,6-dideoxy-D-glucose as the
      substrate provides strong evidence for direct hydrogen atom transfer to a 5'
      deoxyadenosyl radical in the catalytic cycle. The fact that hydrogen atom
      abstraction occurs at C-3 also sheds light on the mechanism of this intriguing
      deamination reaction.

PMID- 19746912
TI  - Dioxygen activation by mononuclear nonheme iron(II) complexes generates iron
      oxygen intermediates in the presence of an NADH analogue and proton.
AB  - One primary goal in biomimetic research is to understand mechanisms of dioxygen
      activation, structures of reactive intermediates, and reactivities of the
      intermediates involved in catalytic oxidation reactions by metalloenzymes, such
      as heme and nonheme iron oxygenases. In this communication, we have reported the
      first example of generating nonheme iron(III)-hydroperoxo and iron(IV)-oxo
      complexes by activating O(2) with a biologically important electron donor, an
      NADH analogue, and an acid. The formation of iron(III)-hydroperoxo and iron(IV)
      oxo complexes was found to depend on the supporting ligands. We have also
      demonstrated that high-spin nonheme iron(II) complexes with a low oxidation
      potential are able to bind and activate O(2) to generate the iron-oxygen
      intermediates.

PMID- 19746913
TI  - 3-4'-Bipiperidines via sequential [4 + 4]-[3,3]-retro-Mannich reactions.
AB  - An approach to assembling unsymmetrically coupled piperidines is described,
      involving initial [4 + 4] photocycloaddition of 2-pyridones, followed by Cope
      rearrangement and retro-Mannich reaction. In these reactions, four stereogenic
      centers set during cycloaddition are relayed or erased during the subsequent
      steps. Two methods for retro-Mannich reaction are demonstrated.

PMID- 19746914
TI  - Gamma-spiroketal gamma-lactones from 2-(gamma-hydroxyalkyl)furans: syntheses of
      epi-pyrenolide D and crassalactone D.
AB  - Photooxygenation of 2-(gamma-hydroxyalkyl)furans followed by dehydration affords,
      in one synthetic operation and in high yield, gamma-spiroketal gamma-lactones.
      This newly developed technology was successfully applied to the synthesis of
      three different epimers of pyrenolide D, as well as to the first synthesis of the
      anticancer natural product crassalactone D and its C4-epimer.

PMID- 19746916
TI  - Highly enantioselective alkylation reaction of enamides by Bronsted-acid
      catalysis.
AB  - The H8-BINOL-derived, phosphoric acid catalyzed, highly enatioselective
      alkylation reaction of enamides with indolyl alcohols has been described. A
      phosphoric acid derived from H8-BINOL enabled an asymmetric alpha-alkylation of
      enamides with indolyl alcohols to give beta-aryl 3-(3-indolyl)propanones in high
      yields (up to 96%) and with excellent enantioselectivity (up to 96% ee).

PMID- 19746915
TI  - A new model for the presentation of tumor-associated antigens and the quest for
      an anticancer vaccine: a solution to the synthesis challenge via ring-closing
      metathesis.
AB  - Fully synthetic, carbohydrate-based antitumor vaccine candidates have been
      synthesized in highly clustered modes. Multiple copies of tumor-associated
      carbohydrate antigens, Tn and STn, were assembled on a single cyclic peptide
      scaffold in a highly convergent manner. Ring-closing metathesis-mediated
      incorporation of an internal cross-linker was also demonstrated. In particular,
      this rigidified cross-linked construct would enhance a cluster-recognizing
      antibody response by retaining an appropriate distance between glycans attached
      to the peptide platform. Details of the design and synthesis of highly clustered
      antigens are described herein.

PMID- 19746917
TI  - Light-independent metabolomics of endophytic Thielavia subthermophila provides
      insight into microbial hypericin biosynthesis.
AB  - The possible microbial mechanism of hypericin (1) and emodin (2) biosynthesis was
      studied in axenic submerged culture conditions in the endophytic fungus Thielavia
      subthermophila, isolated from Hypericum perforatum. The growth and secondary
      metabolite production of the endophyte remained independent of the illumination
      conditions. This production remained unaltered on spiking the medium with 3 or 5
      mM 2, although the biomass accumulation was reduced. Neither emodin anthrone (3)
      nor protohypericin (4) could be detected at any stage of fermentation,
      irrespective of either spiking or illumination conditions. The endophytic
      metabolites exhibited photodynamic cytotoxicity against the human acute monocytic
      leukemia cell line (THP-1), at 92.7 vs 4.9%, and 91.1 vs 1.0% viability by
      resazurin and ATPlite assays, in light and in the dark, respectively. In trying
      to ascertain the presence/expression of the candidate hyp-1 gene in the
      endophyte, it was revealed that the hyp-1 gene was absent in T. subthermophila,
      indicating that the biosynthetic pathway in the endophytic fungus might be
      different and/or governed by a different molecular mechanism than the host plant
      or host cell suspension cultures. We have discussed the biosynthetic principles
      and evolutionary implications relating to endophytic T. subthermophila based on
      the results obtained.

PMID- 19746918
TI  - Multivalent display of quinic acid based ligands for targeting E-selectin
      expressing cells.
AB  - The site-specific expression of molecular markers on endothelial cells of blood
      vessels during inflammatory response and angiogenesis provides an opportunity to
      target drugs and imaging molecules to the vascular endothelium of diseased
      tissues. This paper describes an innovative strategy for selective delivery of
      polymer conjugates to E- and P-selectin expressing cells using a series of quinic
      acid (Qa) based non-carbohydrate analogues of the natural ligand sialyl Lewis(x)
      (sLe(x)) as targeting moieties. We demonstrate that such analogues antagonize the
      adhesion of sLe(x) expressing HL-60 cells to both E- and P-selectin.
      Significantly, the apparent avidity of polymer conjugates carrying multiple Qa
      copies has increased by 3 orders of magnitude relative to their monomeric forms.
      Furthermore, we found that the major mechanism of copolymer entry and delivery
      into E-selectin expressing cells is endocytosis. These selectin-targetable
      copolymers provide the foundation to support controlled delivery of anticancer
      drugs and imaging agents to tumor vasculature for therapeutic and diagnostic
      applications.

PMID- 19746919
TI  - Anti-tumor-promoting effects of 25-methoxyporicoic acid A and other triterpene
      acids from Poria cocos.
AB  - Nine new (1, 3, 5, 8, 12, 13, 15, 17, and 18) and nine known (2, 4, 6, 7, 9-11,
      14, and 16) lanostane-type triterpene acids and a known diterpene acid (19) were
      isolated from the epidermis of the sclerotia of Poria cocos. The structures of
      the new compounds were established as 16alpha,27-dihydroxydehyrotrametenoic acid
      (1), 25-hydroxy-3-epitumulosic acid (3), 16alpha,25-dihydroxyeburiconic acid (5),
      25-methoxyporicoic acid A (8), 26-hydroxyporicoic acid DM (12), 25
      hydroxyporicoic acid C (13), poricoic acid GM (15), poricoic acid HM (17), and
      6,7-dehydroporicoic acid H (18), on the basis of spectroscopic methods. On
      evaluation of the nine new and two of the known compounds, 4 and 19, against the
      Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O
      tetradecanoylphorbol-13-acetate (TPA) in Raji cells, all of the compounds
      exhibited inhibitory effects, with IC(50) values in the range 187-348 mol
      ratio/32 pmol TPA. In addition, compound 8 exhibited an inhibitory effect on skin
      tumor promotion in an in vivo two-stage carcinogenesis test using 7,12
      dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter. Further,
      17 compounds, 1-14, 16, 18, and 19, were evaluated for their cytotoxic activity
      against two human tumor cell lines, HL60 (leukemia) and CRL1579 (melanoma).

PMID- 19746920
TI  - Influence of ripe table olive processing on oil characteristics and composition
      as determined by chemometrics.
AB  - The changes in ripe olive fat produced by processing were studied according to
      cultivars using the general linear model, principal component analysis (PCA),
      predictive discriminant analysis (DA), and hierarchical clustering. Acidity,
      peroxide value, K(270), and DeltaK increased during storage. Acidity also
      increased after sterilization, whereas K(270) decreased after darkening; K(232)
      showed a progressive decrease during processing. Fatty acids (except C17:0,
      C18:0, and C24:0), triacylglycerols (except PLLn, OOLn+PoOL, PLL+PoPoO, SOO, and
      POS+SLS), polar compounds, diacylglycerol, and monoacylglycerols also suffered
      statistically significant changes during processing. A PCA discriminated between
      cultivars and, within the same cultivar, among the raw materials from the rest of
      the treatments. Using fatty acid and triacylglycerol compositions, predictive DA
      discriminated between cultivars (100% correct), but high discriminant capacity
      among processing steps (95% correct assignation and 87% in cross-validation) was
      achieved only with fatty acids. A hierarchical clustering analysis successfully
      grouped cultivars and processing steps according to overall olive oil composition
      and quality.

PMID- 19746921
TI  - Reaction rate coefficients of OH radicals and Cl atoms with ethyl propanoate, n
      propyl propanoate, methyl 2-methylpropanoate, and ethyl n-butanoate.
AB  - Kinetics of the reactions of OH radicals and Cl atoms with four saturated esters
      have been investigated. Rate coefficients for the gas-phase reactions of OH
      radicals with ethyl propanoate (k(1)), n-propyl propanoate (k(2)), methyl 2
      methylpropanoate (k(3)), and ethyl n-butanoate (k(4)) were measured using a
      conventional relative rate method and the pulsed laser photolysis-laser induced
      fluorescence technique. At (296 +/- 2) K, the rate coefficients obtained by the
      two methods were in good agreement. Significant curvatures in the Arrhenius plots
      have been observed in the temperature range 243-372 K for k(1), k(3), and k(4).
      The rate coefficients for the reactions of the four esters with Cl atoms were
      determined using the relative rate method at (296 +/- 2) K and atmospheric
      pressure. The values obtained are presented, compared with the literature values
      when they exist, and discussed. Reactivity trends and atmospheric implications
      for these esters are also presented.

PMID- 19746922
TI  - Dirichlet boundary conditions and effect of confinement on chemical reactivity.
AB  - To understand the source of discrepancy in the qualitative trends in the
      reactivity of the spherically confined atoms/ions when the high pressure is
      generated through the use of a proper Dirichlet boundary condition [J. Chem. Sci.
      2005, 117, 379; Phys. Chem. Chem. Phys. 2008, 10, 1406] and of a cutoff function
      [Chem. Phys. Lett. 2003, 372, 805; J. Phys. Chem. A 2003, 107, 4877], a modified
      Herman-Skilman program is run. Results obtained from different formulas of
      reactivity parameters are analyzed. Change in reactivity for different electronic
      configurations is also reported. It is observed that the use of different
      formulas is the major source of discrepancy and not the Dirichlet condition,
      although the latter is highly recommended. As the cutoff radius of the confining
      spherical box decreases, the energy of the atom/ion increases, the
      electronegativity decreases, and the hardness increases and ultimately slightly
      decreases in an ultraconfined situation. For small R(C) values, softness
      decreases and electrophilicity increases and attains relatively small values. The
      reactivity of confined atoms/ions is put in a proper perspective.

PMID- 19746924
TI  - Selective conversion of alcohols into alkyl iodides using a thioiminium salt.
AB  - Treatment of a range of primary and secondary alcohols with MeSCH=NMe(2)(+) I(-)
      affords the corresponding alkyl iodides in excellent yield with straightforward
      purification. Selective formation of a primary iodide in the presence of a
      secondary alcohol can be achieved.

PMID- 19746925
TI  - Enantioselective synthesis of the R-enantiomer of the feeding deterrent (S)
      ypaoamide.
AB  - The enantioselective synthesis of the R-enantiomer of the marine natural product
      (S)-ypaoamide (5) is reported. The synthesis features both a flexible
      racemization-free approach to the 5-substituted 3-pyrrolin-2-one segment, and a
      lipase (CCL)-promoted deacetylation reaction to reach the orthogonal
      deprotection. Through this work the absolute configuration of the natural
      ypaoamide was determined as S.

PMID- 19746926
TI  - Hg2+-reactive double hydrophilic block copolymer assemblies as novel
      multifunctional fluorescent probes with improved performance.
AB  - We report on novel type of responsive double hydrophilic block copolymer (DHBC)
      based multifunctional chemosensors to Hg(2+) ions, pH, and temperatures and
      investigate the effects of thermo-induced micellization on the detection
      sensitivity. Well-defined DHBCs bearing rhodamine B-based Hg(2+)-reactive
      moieties (RhBHA) in the thermo-responsive block, poly(ethylene oxide)-b-poly(N
      isopropylacrylamide-co-RhBHA) (PEO-b-P(NIPAM-co-RhBHA)), were synthesized via
      reversible addition-fragmentation chain transfer (RAFT) polymerization.
      Nonfluorescent RhBHA moieties are subjected to selective ring-opening reaction
      upon addition of Hg(2+) ions or lowering solution pH, producing highly
      fluorescent acyclic species. Thus, at room temperature PEO-b-P(NIPAM-co-RhBHA)
      DHBCs can serve as water-soluble multifunctional and efficient fluorescent
      chemosensors to Hg(2+) ions and pH. Upon heating above the lower critical
      solution temperature (approximately 36 degrees C) of the PNIPAM block, they self
      assemble into micelles possessing P(NIPAM-co-RhBHA) cores and well-solvated PEO
      coronas, which were fully characterized by dynamic and static laser light
      scattering. It was found that the detection sensitivity to Hg(2+) ions and pH
      could be dramatically improved at elevated temperatures due to fluorescence
      enhancement of RhBHA residues in the acyclic form, which were embedded within
      hydrophobic cores of thermo-induced micellar aggregates. This work represents a
      proof-of-concept example of responsive DHBC-based multifunctional fluorescent
      chemosensors for the highly efficient detection of Hg(2+) ions, pH, and
      temperatures with tunable detection sensitivity. Compared to reaction-based small
      molecule Hg(2+) probes in previous literature reports, the integration of stimuli
      responsive block copolymers with well-developed small molecule-based selective
      sensing moieties in the current study are expected to exhibit preferred
      advantages including enhanced detection sensitivity, water dispersibility,
      biocompatibility, facile incorporation into devices, and the ability of further
      functionalization for targeted imaging and detection.

PMID- 19746927
TI  - Dynamical property of water droplets of different sizes adsorbed onto a
      poly(methyl methacrylate) surface.
AB  - A molecular dynamics approach has been employed to study the dynamical behavior
      of a water droplet adsorbed on a poly(methyl methacrylate) (PMMA) surface.
      Several sizes of water droplets are considered in order to understand the size
      influence of the droplet on the dynamical properties of water molecules on the
      PMMA substrate. The local density profile of water molecules in the droplet upon
      impact with the PMMA surface is calculated, and the result shows an increase in
      water penetration with a decrease in the size of the droplet. By examining the
      velocity field, the regular motion of the water droplet is found both during the
      equilibrium process and after the droplet reaches the equilibrium state. The
      dynamical behavior of water molecule is studied by the velocity autocorrelation
      function (VACF) in different regions for different sizes of water droplets. The
      result shows that VACFs in different regions are significantly influenced for the
      droplet with 500 water molecules than for that with 2000 water molecules.
      Calculations in different regions are made for the vibrational spectrum of the
      oxygen atom, as well as for hydrogen bond dynamics, the lifetime, and the
      relaxation time of the hydrogen bond. The changes in the hydrogen bond dynamics
      are consistent with the change in the distribution of the hydrogen bond angle. We
      conclude that the dynamical properties of the water molecule are significantly
      affected by the region relative to the surface but only weakly influenced by the
      size of the droplet.

PMID- 19746928
TI  - In situ measurements of atmospheric nitrous acid by chemical ionization mass
      spectrometry using chloride ion transfer reactions.
AB  - Recently, chemical ionization mass spectrometry (CIMS) has been widely applied to
      the in situ measurements of atmospheric trace species. In this article, we
      propose a new chemical ionization scheme using a chloride ion transfer reaction
      from SO(2)Cl(-) as the reagent ion and discuss the applicability of this
      technique to the detection of nitrous acid (HONO) in the atmosphere. From
      laboratory investigations, the detection sensitivity was found to depend on the
      flow rate of SO(2) introduced into the ion source region and the pressure inside
      the chemical ionization region, which suggests that the chemical ionization
      reaction is reversible. The detection sensitivity was well described in terms of
      the forward and backward rates. The present limit of detection is estimated to be
      60 parts per trillion by volume (pptv) for an integration time of 1 min.
      Improvement of the CIMS instrument would enable the measurements of the daytime
      level of HONO, which might be less than 50 pptv. In addition, the possibility of
      the interference is discussed from thermodynamic considerations based on ab
      initio calculations, and the effects of the sampling artifacts are experimentally
      quantified.

PMID- 19746929
TI  - Highly efficient light-harvesting ruthenium sensitizer for thin-film dye
      sensitized solar cells.
AB  - A high molar extinction coefficient heteroleptic ruthenium complex, incorporating
      an electron-rich hexylthio-terminal chain, has been synthesized and demonstrated
      as an efficient sensitizer for dye-sensitized solar cells. With this new
      sensitizer excellent power conversion efficiency is 11.5% and 4.7% obtained under
      an irradiation of full sunlight (air mass 1.5 global) in combination with a
      volatility electrolyte and solid state hole transporting material, respectively.
      The devices with low volatility electrolyte showed good stability under visible
      light soaking at 60 degrees C during 1000 h of accelerated tests.

PMID- 19746931
TI  - Gold nanoparticle arrangement on viral particles through carbohydrate
      recognition: a non-cross-linking approach to optical virus detection.
AB  - We propose a new approach to optical virus detection based on the spatial
      assembly of gold nanoparticles on the surface of viruses. Since JC virus-like
      particles (VLPs) comprise a repeating viral capsid protein that binds to sialic
      acid, the conjugation of sialic acid-linked Au particles with VLPs enables the
      spatial arrangement of Au particles on the VLP surface. This structure produced a
      red shift in the absorption spectrum due to plasmon coupling between adjacent Au
      particles, leading to the construction of an optical virus detection system. Our
      system depends not on the simple cross-linking of VLPs and Au particles, but on
      an ordered Au structure covering the entire surface of the VLPs and can be
      applied to various virus detection systems using the inherent ligand recognition
      of animal viruses.

PMID- 19746930
TI  - Pyrroloquinoline quinone biogenesis: demonstration that PqqE from Klebsiella
      pneumoniae is a radical S-adenosyl-L-methionine enzyme.
AB  - Biogenesis of pyrroloquinoline quinone (PQQ) in Klebsiella pneumoniae requires
      the expression of six genes (pqqA-F). One of these genes (pqqE) encodes a 43 kDa
      protein (PqqE) that plays a role in the initial steps in PQQ formation [Veletrop,
      J. S., et al. (1995) J. Bacteriol. 177, 5088-5098]. PqqE contains two highly
      conserved cysteine motifs at the N- and C-termini, with the N-terminal motif
      comprised of a CX(3)CX(2)C consensus sequence that is unique to a family of
      proteins known as radical S-adenosyl-l-methionine (SAM) enzymes [Sofia, H. J., et
      al. (2001) Nucleic Acids Res. 29, 1097-1106]. PqqE from K. pneumoniae was cloned
      into Escherichia coli and expressed as the native protein and with an N-terminal
      His(6) tag. Anaerobic expression and purification of the His(6)-tagged PqqE
      results in an enzyme with a brownish-red hue indicative of Fe-S cluster
      formation. Spectroscopic and physical analyses indicate that PqqE contains a
      mixture of Fe-S clusters, with the predominant form of the enzyme containing two
      [4Fe-4S] clusters. PqqE isolated anaerobically yields an active enzyme capable of
      cleaving SAM to methionine and 5'-deoxyadenosine in an uncoupled reaction (k(obs)
      = 0.011 +/- 0.001 min(-1)). In this reaction, the 5'-deoxyadenosyl radical either
      abstracts a hydrogen atom from a solvent accessible position in the enzyme or
      obtains a proton and electron from buffer. The putative PQQ substrate PqqA has
      not yet been shown to be modified by PqqE, implying that PqqA must be modified
      before becoming the substrate for PqqE and/or that another protein in the
      biosynthetic pathway is critical for the initial steps in PQQ biogenesis.

PMID- 19746932
TI  - Oxidatively damaged nucleobases in duplex DNA oligomers: reaction at thymine
      thymine mispairs.
AB  - Thymine-thymine mispairs are barriers to long-distance radical cation migration
      and are high reactivity sites in duplex DNA oligomers. A DNA oligomer was
      prepared that contains only A/T base pairs, arranged into a regularly repeating
      series of TT steps, and a covalently linked anthraquinone photosensitizer. Its UV
      irradiation causes the one-electron oxidation of the DNA introducing a radical
      cation that reacts predominantly at the TT steps as revealed by subsequent strand
      cleavage. When a remote GG step is introduced into the DNA oligomer, there is
      little reaction at any of the TT steps and strand cleavage is detected almost
      exclusively at the GG step. However, when a TT step contains a thymine-thymine
      mispair, one electron oxidation of the oligomer results in strand cleavage at the
      mispair and at TT steps preceding it with little reaction at the remote GG step.
      Experiments in which a thymine in the mispair is replaced by uracil show that the
      mispair is both a highly reactive site and a barrier to radical cation hopping.
      These effects of the thymine-thymine mispairs may be associated with its wobble
      base pair structure.

PMID- 19746933
TI  - Proton-driven amide bond-cleavage pathways of gas-phase peptide ions lacking
      mobile protons.
AB  - The mobile proton model (Dongre, A. R., Jones, J. L., Somogyi, A. and Wysocki, V.
      H. J. Am. Chem. Soc. 1996, 118 , 8365-8374) of peptide fragmentation states that
      the ionizing protons play a critical role in the gas-phase fragmentation of
      protonated peptides upon collision-induced dissociation (CID). The model
      distinguishes two classes of peptide ions, those with or without easily
      mobilizable protons. For the former class mild excitation leads to proton
      transfer reactions which populate amide nitrogen protonation sites. This enables
      facile amide bond cleavage and thus the formation of b and y sequence ions. In
      contrast, the latter class of peptide ions contains strongly basic
      functionalities which sequester the ionizing protons, thereby often hindering
      formation of sequence ions. Here we describe the proton-driven amide bond
      cleavages necessary to produce b and y ions from peptide ions lacking easily
      mobilizable protons. We show that this important class of peptide ions fragments
      by different means from those with easily mobilizable protons. We present three
      new amide bond cleavage mechanisms which involve salt-bridge, anhydride, and
      imine enol intermediates, respectively. All three new mechanisms are less
      energetically demanding than the classical oxazolone b(n)-y(m) pathway. These
      mechanisms offer an explanation for the formation of b and y ions from peptide
      ions with sequestered ionizing protons which are routinely fragmented in large
      scale proteomics experiments.

PMID- 19746934
TI  - Discovery of new inhibitors of resistant Streptococcus pneumoniae penicillin
      binding protein (PBP) 2x by structure-based virtual screening.
AB  - Penicillin binding proteins (PBPs) are involved in the biosynthesis of the
      peptidoglycan layer constitutive of the bacterial envelope. They have been
      targeted for more than half a century by extensively derived molecular scaffolds
      of penicillins and cephalosporins. Streptococcus pneumoniae resists the
      antibiotic pressure by inducing highly mutated PBPs that can no longer bind the
      beta-lactam containing agents. To find inhibitors of PBP2x from Streptococcus
      pneumoniae (spPBP2x) with novel chemical scaffold so as to circumvent the
      resistance problems, a hierarchical virtual screening procedure was performed on
      the NCI database containing approximately 260000 compounds. The calculations
      involved ligand-based pharmacophore mapping studies and molecular docking
      simulations in a homology model of spPBP2x from the highly resistant strain 5204.
      A total of 160 hits were found, and 55 were available for experimental tests.
      Three compounds harboring two novel chemical scaffolds were identified as
      inhibitors of the resistant strain 5204-spPBP2x at the micromolar range.

PMID- 19746935
TI  - Voltammetric extraction of heparin and low-molecular-weight heparin across 1,2
      dichloroethane/water interfaces.
AB  - Heparin and low-molecular-weight heparin are voltammetrically extracted across
      1,2-dichloroethane/water interfaces for the detection of these highly sulfated
      polysaccharides widely used as anticoagulants/antithrombotics in many medical
      procedures. A new heparin ionophore, 1-[4
      (dioctadecylcarbamoyl)butyl]guanidinium, is the first to enable the voltammetric
      extraction of various polyanionic heparins with average molecular weights of up
      to approximately 20 kDa including those in commercial preparations (i.e., Arixtra
      (1.5 kDa), Lovenox (4.5 kDa), and unfractionated heparin (15 kDa), as well as
      chromatographically fractionated heparins (7, 9, 15, and 20 kDa)). Facilitated
      Arixtra extraction is fully and quantitatively characterized by micropipet
      voltammetry to propose that cooperative effects from strong heparin-binding
      capability and high lipophilicity of this ionophore are required for the
      formation of an electrically neutral and highly lipophilic complex of a heparin
      molecule with multiple ionophore molecules to be extracted into the nonpolar
      organic phase. At the same time, the participation of multiple ionophore
      molecules in interfacial complexation with a heparin molecule slows down its
      extraction across the interface. This kinetic limitation is enhanced by fast mass
      transfer at a micropipet-supported interface to compromise thermodynamically
      favorable selectivity for heparin and an important contaminant, oversulfated
      chondroitin sulfate, thereby requiring a macroscopic interface for sensing
      applications. Another highly lipophilic guanidinium ionophore, N,N
      dioctadecylguanidinium, cannot completely extract even Arixtra, which indicates
      the importance of elaborate ionophore design for heparin extraction.

PMID- 19746936
TI  - Generator-collector experiments at a single electrode: exploring the general
      applicability of this approach by comparing the performance of surface
      immobilized versus solution phase sensing molecules.
AB  - We demonstrate proof-of-concept that generator-collector experiments can be
      performed at a single macroelectrode and used to determine mechanistic
      information. The practical advantages of such a system over conventional
      generator-collector techniques are also outlined. The single-electrode generator
      collector technique is applied to study the known mechanism of oxygen reduction
      in aqueous conditions as a model system. We seek to demonstrate that the single
      electrode generator-collector approach is capable of detecting local pH changes,
      immediately adjacent to the electrode surface during a redox reaction.
      Experiments are performed using a molecular pH probe attached to the electrode
      surface. Comparison of experimental data with numerical simulations verifies that
      the reduction of oxygen at pH 6.8 proceeds via a two-electron, two-proton
      mechanism. Experiments were also performed with a molecular pH probe dissolved in
      the electrolyte solution in order to explore the feasibility of this approach,
      which is potentially applicable to a much wider range of electrochemical systems.

PMID- 19746937
TI  - Mesoporous zirconium titanium oxides. Part 3. Synthesis and adsorption properties
      of unfunctionalized and phosphonate-functionalized hierarchical polyacrylonitrile
      F-127-templated beads.
AB  - A method is presented for the preparation of zirconium titanate mixed oxides in
      bead form having hierarchical pore structure. This method entailed the use of
      both preformed polyacrylonitrile (PAN) polymer beads and surfactants as
      templates. The templates were removed by calcination at temperatures below about
      500 degrees C, resulting in mixed oxide beads with trimodal pore size
      distributions and interconnected pores. The pore size distributions as determined
      using nitrogen adsorption-desorption showed clear maxima at 4.5 and 45 nm length
      scales and also clear evidence of microporosity. The macroporous framework
      morphology was a replica of the PAN beads with radial structure. The mesoporous
      framework possessed wormhole-like pores with pore size of about 6 nm that was
      consistent with the F-127 triblock copolymer template used. The mixed oxide beads
      exhibited surface areas of 215 and 185 m2/g after calcination at 500 and 600
      degrees C. Thermal stability up to 650 degrees C is unprecedented for bulk
      systems. The adsorption properties were characterized using uranyl as the target
      cation and the mass transport in the beads with the present hierarchical
      architectures has been shown to be exceptional. The beads were functionalized
      with 4-amino,1-hydroxy,1,1-bis-phosphonic acid (HABDP) and amino-tris-methylene
      phosphonic acid (ATMP) and the adsorption properties for the extraction of uranyl
      sulfate complexes from acidic solution examined. Of the two molecules
      investigated, ATMP functionalization resulted in the best extraction efficiency
      with equilibrium uptake of about 90% of uranium available in solution between pH
      1 and 2. The beads could potentially be utilized as catalysts, catalyst supports,
      adsorbents, and separation materials.

PMID- 19746938
TI  - Morphological transitions of liquid droplets on circular surface domains.
AB  - We study morphological transitions of droplets on a structured substrate
      containing two circular lyophilic domains for arbitrary domain and substrate
      wettabilities. We derive the stability criterion that at least one of the
      droplets must be pinned at the domain boundary with a contact angle smaller than
      (pi)/(2). This determines seven classes of stable or metastable droplet
      morphologies of the system. We present a complete classification of stability and
      metastability of these morphologies as a function of three control parameters as
      provided by the total droplet volume, substrate wettability, and domain
      wettability. We find different types of morphological transitions at the
      stability boundaries: (i) depinning transitions of the contact lines, (ii)
      symmetry-breaking transitions, where the two droplets acquire different volumes,
      and (iii) dewetting transitions, where one domain dewets and one of the droplets
      disappears. We find that depinning transitions of two droplets become
      discontinuous between two universal values of substrate wettability. Furthermore,
      below a critical domain wettability, one domain always dewets irrespective of the
      total volume. We discuss experimental realizations and applications of our
      results for controlled switching between observed wetting morphologies.

PMID- 19746939
TI  - A systematic and quantitative study of the link between foam slipping and
      interfacial viscoelasticity.
AB  - Aqueous foams are often used under various flow regimes, and one of the biggest
      challenges is to create predictive models of their complex rheological
      properties. Previous theoretical and experimental studies have qualitatively
      characterized the wall slip of foams. We focus on this phenomenon in a 1D
      geometry, studying the friction force to move a train of foam films in a narrow
      channel. We perform, and correlate, 1D experiments and interfacial measurements
      of surface elasticity. We adapt existing models to correctly analyze and
      interpret 1D data, allowing for comparison with 3D foam slip results. Different
      mixtures of surfactants allow us to quantify the influence of interfacial
      properties. In particular, we show for 1D experiments that already with a low
      elasticity, of order 1 mN m(-1), we leave the regime where the interface can be
      considered as fluid, to enter a regime where dissipation depends only marginally
      on surface elasticity.

PMID- 19746940
TI  - Intracellular biogenic silver nanoparticles for the generation of carbon
      supported antiviral and sustained bactericidal agents.
AB  - Intracellular silver nanoparticles produced by exposing silver ions to the fungus
      Aspergillus ochraceus were heat-treated in nitrogen environment to yield silver
      nanoparticles embedded in carbonaceous supports. This carbonaceous matrix
      embedded silver nanoparticles showed antimicrobial properties against both
      bacteria (Gram-positive and Gram-negative) and virus (M 13 phage virus). The
      bactericidal effects were noticed even after washing and repeated exposure of
      these carbon supported silver nanoparticles to fresh bacterial cultures,
      revealing their sustained activity.

PMID- 19746941
TI  - Enhancement mechanism of electrochemical capacitance in nitrogen-/boron-doped
      carbons with uniform straight nanochannels.
AB  - Anodic aluminum oxide (AAO) with uniform straight nanochannels was completely
      coated with pure, N-doped, or B-doped carbon layer. Their electric double layer
      capacitances are measured in aqueous (1 M sulfuric acid) and organic (1 M
      Et4NBF4/polypropylene carbonate) electrolyte solutions in order to investigate
      the capacitance enhancement mechanisms caused by N- or B-doping. Since the three
      types of carbon-coated AAOs (pure, N-doped, or B-doped) have exactly the same
      pore structure, the observed capacitance enhancement was ascribable to only the
      following factors: (i) better wettability, (ii) the decrease of equivalent series
      resistance, (iii) the contribution of space-charge-layer capacitance, and (iv)
      the occurrence of pseudocapacitance. From the measurements of the wettability and
      the electrical resistance of the coated AAOs together with the electrochemical
      investigation (the cyclic voltammetry, the galvanostatic charge/discharge
      cycling, and the impedance analysis), it is concluded that the pseudocapacitance
      through faradic charge transfer (factor iv) is the most important factor to
      enhance the capacitance by N- or B-doping. This can be applied to not only the
      present carbon-coated AAOs but also any other porous carbons.

PMID- 19746942
TI  - Interaction of cationic hydrophobic surfactants at negatively charged surfaces
      investigated by atomic force microscopy.
AB  - Atomic force microscopy was used to study the adsorption of the surfactant
      octadecyl trimethyl ammonium chloride (C18TAC) at a low concentration (0.03 mM)
      to negatively charged surfaces in water. Atomic force microscopy tips were
      functionalized with dimethyloctadecyl(3-tripropyl)ammonium chloride (C18TAC-si)
      or N-trimethoxysilylpropyl-N,N,N-trimethylammomium chloride (hydrophilpos-si) to
      facilitate imaging of the adsorbed surfactant without artifacts. Tapping mode
      images and force measurements revealed C18TAC patches, identified as partial
      surfactant bilayers or hemimicelles. The forces controlling the adsorption
      process of the C18TAC to a negatively charged surface were investigated by
      measuring the forces between a C18TAC-si or a hydrophilpos-si tip and a silica
      surface in the presence of varying concentrations of either NaCl or NaNO3.
      Screening of forces with an increasing NaCl concentration was observed for the
      C18TAC-si and hydrophilpos-si tips, proving an electrostatic contribution.
      Screening was also observed for the hydrophilpos-si tip in NaNO3, whereas a long
      range attraction was observed for the C18TAC-si tip for all NaNO3 concentrations.
      These results indicate that screening of the forces for the C18TAC-si tip
      depended on the type and/or size of the anion, possibly due to a different
      probability of the anions to enter the silane layers. The interaction of C18TAC
      patches with C18TAC-si tips in the presence of NaCl and the interaction of the
      patches with hydrophilpos-si tips in either NaCl or NaNO3 were repulsive and
      independent of the number of force curves measured, indicating a stable,
      positively charged C18TAC patch. However, the forces measured between the patches
      and a C18TAC-si tip in NaNO3 depended on the number of force curves measured,
      indicating a change in patch structure induced by the first interaction.

PMID- 19746943
TI  - (+)-Zwittermicin A. Rapid assembly of C9-C15 and a formal total synthesis.
AB  - A short, enantioselective synthesis of the C9-C15 portion of (+)-zwittermicin A
      is reported that exploits directional functionalization of the known hepta-2,5
      diyne-1,7-diol by partial reduction of the two triple bonds followed by Sharpless
      asymmetric epoxidation and boron-directed double ring-opening with sodium azide
      under Miyashita conditions. Subsequent desymmetrization of the C(2)-symmetric
      diazidotetraol product converges upon (-)-3--the enantiomer of the key
      intermediate of our earlier structural proof and synthesis of (-)-zwittermicin A-
      and constitutes a formal synthesis of (+)-zwitttermicin A.

PMID- 19746944
TI  - Comparison of vesicle formation in zwitanionic and catanionic mixtures of
      hydrocarbon and fluorocarbon surfactants: phase behavior and structural
      progression.
AB  - The phase behavior of zwitanionic and catanionic mixtures of perfluoro and
      hydrocarbon surfactants has been studied for the case of lithium
      perfluorooctanoate (LiPFO) as anionic surfactant and tetradecyldimethylamine
      oxide (TDMAO) as zwitterionic or tetradecyltrimethyl ammonium bromide (TTAB) as
      cationic surfactant. Samples as a function of the mixing ratio were characterized
      by means of electric conductivity, light scattering, cryo-TEM, and rheology.
      Despite the equal chain length of the zwitterionic and cationic surfactant we
      observe largely different phase behavior in these systems with the formation of
      precipitates around equimolar mixing for the catanionic system, while no such
      precipitation is observed for the zwitanionic system. This can be rationalized in
      terms of the much lower interaction parameter beta (from cmc measurements) for
      the case of the zwitanionic system. Accordingly, in the zwitanionic mixture a
      larger range of stable unilamellar vesicles is observed, while for the catanionic
      system larger vesicles are present, with a much stronger tendency for formation
      of multilamellar vesicles. Another interesting effect is that only for the case
      of the zwitanionic mixture a substantial increase of viscosity is observed prior
      to the formation of vesicles, which means that here the transition from spherical
      micelles to vesicles takes place via strongly anisometric micellar aggregates,
      which are not observed for the case of the catanionic mixtures. From these
      results it can be concluded that the structure and stability of vesicles formed
      in these mixtures are largely controlled by the extent of the electrostatic
      interactions which allows modification accordingly.

PMID- 19746946
TI  - Molecular rotational excitation by strong femtosecond laser pulses.
AB  - We study the rotational wave packet created by nonadiabatic rotational excitation
      of molecules with strong femtosecond laser pulses. The applicable condition of
      the Delta-Kick method is obtained by comparing the laser intensity and pulse
      duration dependences of the wave packet calculated with different methods. The
      wave packet evolution is traced analytically with the Delta-Kick method. The
      calculations demonstrate that the rotational populations can be controlled for
      the rotational wave packet created by two femtosecond laser pulses. The evolution
      of the rotational wave packet with controlled populations produces interference
      patterns with exotic spatial symmetries. These calculations are validated by
      comparing the theoretical calculations with our experimental measurements for the
      rotational wave packet created by thermal ensemble CO(2) and two strong
      femtosecond laser pulses. Potential applications in molecular science are also
      discussed for the rotational wave packet with controlled populations and spatial
      symmetries.

PMID- 19746945
TI  - Conformation of the phosphate D-alanine zwitterion in bacterial teichoic acid
      from nuclear magnetic resonance spectroscopy.
AB  - The conformation of d-alanine (d-Ala) groups of bacterial teichoic acid is a
      central, yet untested, paradigm of microbiology. The d-Ala binds via the C
      terminus, thereby allowing the amine to exist as a free cationic NH(3)(+) group
      with the ability to form a contact ion pair with the nearby anionic phosphate
      group. This conformation hinders metal chelation by the phosphate because the
      zwitterion pair is charge neutral. To the contrary, the repulsion of cationic
      antimicrobial peptides (CAMPs) is attributed to the presence of the d-Ala cation;
      thus the ion pair does not form in this model. Solid-state nuclear magnetic
      resonance (NMR) spectroscopy has been used to measure the distance between amine
      and phosphate groups within cell wall fragments of Bacillus subtilis. The
      bacteria were grown on media containing (15)N d-Ala and beta-chloroalanine
      racemase inhibitor. The rotational-echo double-resonance (REDOR) pulse sequence
      was used to measure the internuclear dipolar coupling, and the results
      demonstrate (1) the metal-free amine-to-phosphate distance is 4.4 A and (2) the
      amine-to-phosphate distance increases to 5.4 A in the presence of Mg(2+) ions. As
      a result, the zwitterion exists in a nitrogen-oxygen ion pair configuration
      providing teichoic acid with a positive charge to repel CAMPs. Additionally, the
      amine of d-Ala does not prevent magnesium chelation in contradiction to the
      prevailing view of teichoic acids in metal binding. Thus, the NMR-based
      description of teichoic acid structure resolves the contradictory models,
      advances the basic understanding of cell wall biochemistry, and provides possible
      insight into the creation of new antibiotic therapies.

PMID- 19746947
TI  - Theoretical assessment of norfloxacin redox and photochemistry.
AB  - Norfloxacin, 1-ethyl-6-fluoro-1,4-dihydo-4-oxo-7-(1-piperazinyl)-3
      quinolinecarboxylic acid, NOR, is an antibiotic drug from the fluoroquinoline
      family. The different protonation states of this drug formed throughout the pH
      range is studied by means of density functional theory (DFT) and the spectra of
      the NOR species computed using time-dependent DFT. Details about their
      photochemistry are obtained from investigating the highest occupied and lowest
      unoccupied molecular orbitals. The predominant species under physiological pH,
      the zwitterion, is the most photoliable one, capable of producing singlet oxygen
      or/and superoxide radical anions from its triplet state. In addition, the main
      photodegradation step, defluorination, occurs more easily from this species
      compared with the other forms. The defluorination from the excited triplet state
      requires passing a barrier of 16.3 kcal/mol in the case of the zwitterion. The
      neutral and cationic forms display higher transition barriers, whereas the
      reaction path of defluorination is completely endothermic for the anionic
      species. The theoretical results obtained herein are in line with previous
      experimental data.

PMID- 19746948
TI  - Near resonance charge exchange in ion-atom collisions of lithium isotopes.
AB  - Collisions of ions and atoms of (6)Li and (7)Li are explored theoretically over a
      wide range of energy from 10(-14) to 1 eV. Accurate ab initio calculations are
      carried out of the Born-Oppenheimer potentials and the nonadiabatic couplings
      that are responsible for the near resonance charge exchange. Scattering studies
      show that the calculated charge exchange cross section follows Wigner's law for
      inelastic processes for energies below 10(-10) eV and that the zero temperature
      rate constant for it is 2.1 x 10(-9) cm(3) s(-1). At collision energies much
      larger than the isotope shift of the ionization potentials of the atoms, we show
      that the near resonance charge exchange process is equivalent to the resonance
      charge exchange with cross sections having a logarithmic dependence on energy. A
      comparison with the Langevin model at intermediate energies is also presented.

PMID- 19746949
TI  - NMR chemical shielding and spin-spin coupling constants of liquid NH3: a
      systematic investigation using the sequential QM/MM method.
AB  - The NMR spin coupling parameters, (1)J(N,H) and (2)J(H,H), and the chemical
      shielding, sigma((15)N), of liquid ammonia are studied from a combined and
      sequential QM/MM methodology. Monte Carlo simulations are performed to generate
      statistically uncorrelated configurations that are submitted to density
      functional theory calculations. Two different Lennard-Jones potentials are used
      in the liquid simulations. Electronic polarization is included in these two
      potentials via an iterative procedure with and without geometry relaxation, and
      the influence on the calculated properties are analyzed. B3LYP/aug-cc-pVTZ-J
      calculations were used to compute the (1)J(N,H) constants in the interval of 
      67.8 to -63.9 Hz, depending on the theoretical model used. These can be compared
      with the experimental results of -61.6 Hz. For the (2)J(H,H) coupling the
      theoretical results vary between -10.6 to -13.01 Hz. The indirect experimental
      result derived from partially deuterated liquid is -11.1 Hz. Inclusion of
      explicit hydrogen bonded molecules gives a small but important contribution. The
      vapor-to-liquid shifts are also considered. This shift is calculated to be
      negligible for (1)J(N,H) in agreement with experiment. This is rationalized as a
      cancellation of the geometry relaxation and pure solvent effects. For the
      chemical shielding, sigma((15)N) calculations at the B3LYP/aug-pcS-3 show that
      the vapor-to-liquid chemical shift requires the explicit use of solvent
      molecules. Considering only one ammonia molecule in an electrostatic embedding
      gives a wrong sign for the chemical shift that is corrected only with the use of
      explicit additional molecules. The best result calculated for the vapor to liquid
      chemical shift Delta sigma((15)N) is -25.2 ppm, in good agreement with the
      experimental value of -22.6 ppm.

PMID- 19746950
TI  - Primary kinetic isotope effects on hydride transfer from heterocyclic compounds
      to NAD(+) analogues.
AB  - Primary kinetic isotope effects (KIEs), k(H)/k(D), have been determined
      spectrophotometrically for the reactions of NAD(+) analogues (acridinium ions, 1a
      e(+), and quinolinium ion, 2(+)) with heteroaromatic compounds such as 3-methyl-2
      phenylbenzothiazoline, 3H(D), and 1,3-dimethyl-2-phenylbenzimidazoline, 4H(D) in
      a mixed solvent containing four parts 2-propanol and one part water at 25.0 +/-
      0.1 degrees C. The KIEs decrease from 6.24 to 3.93 as the equilibrium constant,
      K, is increased from about 1 to 10(12) by the structural variation in the hydride
      acceptor. The Marcus theory of atom transfer in a linear, triatomic model of the
      reaction, with tunneling, can explain the variation of KIE with K. The Marcus
      theory is based on a model involving no high-energy intermediates, leading to a
      one-step mechanism. The present system satisfies this condition.

PMID- 19746951
TI  - Triplet-state acid-base reactions of 1-methyl-7-oxyquinolinium in water.
AB  - Upon absorption of a photon, the 1-methyl-7-oxyquinolinium zwitterion in neutral
      water undergoes a proton-transfer cycle involving protonation at the lowest
      excited triplet state and redeprotonation at the ground state. On one hand, the
      proton transfer of a water molecule to the triplet-state zwitterion takes place
      on the time scale of 28 micros with an activation energy of 12.6 kJ mol(-1). On
      the other hand, the ground-state redeprotonation occurs with a rate constant of
      (13 micros)(-1), although its reverse reaction of protonation competes with a
      rate constant of (37 micros)(-1).

PMID- 19746952
TI  - Tunable refractive index sensor with ultracompact structure twisted by
      poly(trimethylene terephthalate) nanowires.
AB  - We report a tunable refractive index sensor with ultracompact structure in a 2 x
      2 poly(trimethylene terephthalate) (PTT) nanowire coupling splitter assembled by
      twisting two flexible PTT nanowires. The sensor consists of two input branches, a
      twisted coupling region, and two output branches. The changes of optical power
      caused due to variations in the surrounding medium around the twisted coupling
      region were measured in the output branches. The highest measured sensitivity of
      the sensor is 26.96 mW/RIU (refractive index unit) and the maximum detection
      limit on refractive index change is 1.85 x 10(-7). The average tunabilities
      observed are 1.2 mW per RIU per twisted turn and 1.8 mW per RIU per 5 degrees
      branching angle change.

PMID- 19746953
TI  - Ordering of poly(3-hexylthiophene) nanocrystallites on the basis of substrate
      surface energy.
AB  - Molecular dynamics simulations are used to study the influence of functionalized
      substrates on the orientation of poly(3-hexylthiophene) (P3HT) nanocrystallites,
      which in turn plays a critical role in P3HT-based transistor performance. The
      effects of alkyl-trichlorosilane self-assembled monolayer packing density,
      packing order, and end-group functionality are independently investigated. Across
      these factors, the potential energy surface presented by the substrate to the
      P3HT molecules is determined to be the main driver of P3HT ordering.
      Surprisingly, disordered substrates with a smoothly varying potential energy
      landscape are found to encourage edge-on P3HT orientation, while highly ordered
      substrates have undesirable potential energy wells that reduce the edge-on
      orientation of P3HT because of substrate-side-chain interactions.

PMID- 19746954
TI  - Synthesis, characterization, and electrochemistry of a series of iron(II)
      complexes containing self-assembled 1,5-diaza-3,7-diphosphabicyclo[3.3.1]nonane
      ligands.
AB  - The reaction between PPh(CH(2)OH)(2), iron(II) sulfate, ammonium sulfate, and
      formaldehyde in aqueous solution gives the iron(II) complex [Fe(kappa(2)
      O(2)SO(2))L(2)] (1), where L is the bidentate phosphine ligand 3,7-diphenyl-1,5
      diaza-3,7-diphosphabicyclo[3.3.1]nonane. During the course of the reaction, the
      ligand L self-assembles on the metal center. The reaction between
      PPh(CH(2)OH)(2), iron(II) chloride, ammonium chloride, and formaldehyde under
      similar conditions gives cis-[FeCl(2)L(2)] (cis-2). The complex cis-2 is
      converted into trans-2 in Et(2)O, whereas in water it is converted into cis
      [Fe(OH(2))(2)L(2)](2+), though both of these interconversions are reversible. The
      chloro ligands in cis-2 are readily displaced by reaction with thiocyanate,
      azide, and carbonate to give cis- and trans-[Fe(NCS)(2)L(2)] (cis- and trans-3),
      cis- and trans-[Fe(N(3))(2)L(2)] (cis- and trans-4), and [Fe(kappa(2)
      O(2)CO)L(2)] (5), respectively. The complex cis-2 reacts with CO in water to give
      trans-[FeCl(CO)L(2)]Cl (trans-6), whereas trans-2 reacts with CO in diethyl ether
      to give cis-[FeCl(CO)L(2)]Cl (cis-6), though cis-6 isomerizes in water to form
      trans-6. The reaction of cis-2 with sodium borohydride gives the hydride chloride
      complex trans-[FeCl(H)L(2)] (7). Electrochemical studies have been undertaken on
      complexes 1, cis-2, and 7. These reveal reversible oxidations for cis-2 and 7,
      with the latter giving rise to an unusual 17-electron iron(III) hydride chloride
      complex. Crystal structures have been obtained for 1, trans-2, trans-3, 5, and 7.

PMID- 19746955
TI  - Collision-energy-resolved penning ionization electron spectroscopy of glycine
      with He(2(3)S) metastable atoms: conformational isomers in collisional
      ionization.
AB  - Conformationally dependent ionization of the simplest amino acid, glycine, is
      studied by Penning ionization electron spectroscopy with velocity-resolved
      metastable He*(2(3)S) atoms. The observed He I ultraviolet photoelectron and
      Penning ionization electron spectra are reproduced by superimposed theoretical
      spectra, assuming thermal distributions of conformers. The conformations of amino
      acids are determined by analyzing the observed Penning ionization cross sections,
      peak shifts, and collision energy dependences of partial ionization cross
      sections (CEDPICS). The Penning ionization cross sections are governed by
      collisionally accessible exterior electron densities. When the amino and carbonyl
      groups are exposed to He* access, the nonbonding orbitals of N (n(N)) and O atoms
      (n(O)) give rise to strong bands. The observed negative peak shifts and negative
      CEDPICS for the n(N) and n(O) orbitals suggest the presence of attractive
      interactions around their electron distributions. The most attractive wells are
      estimated to be approximately 400 meV in the direction of the n(N) orbitals by ab
      initio model calculations. A conformer possessing dual hydrogen bonds contributes
      predominantly to the spectra.

PMID- 19746956
TI  - Experimental and theoretical study of the structures and enthalpies of formation
      of the synthetic reagents 1,3-thiazolidine-2-thione and 1,3-oxazolidine-2-thione.
AB  - This paper reports an experimental and a theoretical study of the structures and
      standard (p(o) = 0.1 MPa) molar enthalpies of formation of the synthetic reagents
      1,3-thiazolidine-2-thione [CAS 96-53-7] and 1,3-oxazolidine-2-thione [CAS 5840-81
      3]. The enthalpies of combustion and sublimation were measured by rotary bomb
      combustion calorimetry, and the Knudsen effusion technique and gas-phase
      enthalpies of formation values at T = 298.15 K of (97.1 +/- 4.0) and -(74.4 +/-
      4.6) kJ.mol(-1) for 1,3-thiazolidine-2-thione and 1,3-oxazolidine-2-thione,
      respectively, were determined. G3-calculated enthalpies of formation are in
      reasonable agreement with the experimental values. In the solid state, 1,3
      thiazolidine-2-thione exists in two polymorphic forms (monoclinic and triclinic)
      and 1,3-oxazolidine-2-thione exits in the triclinic form. The isostructural
      nature of these compounds and comparison of their molecular and crystal
      structures have been analyzed. The experimental X-ray powder diffractograms have
      been compared with the calculated patterns from their structures for
      identification of the polymorphic samples used in this study. A comparison of our
      results with literature thermochemical and structural data for related compounds
      is also reported.

PMID- 19746957
TI  - Quaternary diffusion coefficients in a protein-polymer-salt-water system
      determined by rayleigh interferometry.
AB  - We have experimentally investigated multicomponent diffusion in a protein-polymer
      salt-water quaternary system. Specifically, we have measured the nine
      multicomponent diffusion coefficients, D(ij), for the lysozyme-poly(ethylene
      glycol)-NaCl-water system at pH 4.5 and 25 degrees C using precision Rayleigh
      interferometry. Lysozyme is a model protein for protein-crystallization and
      enzymology studies. We find that the protein diffusion coefficient, D(11),
      decreases as polymer concentration increases at a given salt concentration. This
      behavior can be quantitatively related to the corresponding increase in fluid
      viscosity only at low polymer concentration. However, at high polymer
      concentration (250 g/L), protein diffusion is enhanced compared to the
      corresponding viscosity prediction. We also find that a protein concentration
      gradient induces salt diffusion from high to low protein concentration. This
      effect increases in the presence of poly(ethylene glycol). Finally, we have
      evaluated systematic errors associated with measurements of protein diffusion
      coefficients by dynamic light scattering. This work overall helps characterize
      protein diffusion in crowded environments and may provide guidance for further
      theoretical developments in the field of protein crystallization and protein
      diffusion in such crowded systems, such as the cytoplasm of living cells.

PMID- 19746958
TI  - Effects of ionic liquids on enzymatic catalysis of the glucose oxidase toward the
      oxidation of glucose.
AB  - The effects of ionic liquids (ILs) on the catalytic activity of enzymes were
      studied by approaches of electrochemistry and quantum chemistry calculation in
      this work. Three types of ILs, namely, [bmpyri]BF(4), [bmpyrro]BF(4), and
      [bmim]BF(4), were selected to address the effects of different types of ILs on
      the electrocatalytic activity of glucose oxidase (GOx) toward the oxidation of
      glucose. ILs and GOx were assembled on the surface of an electrode via single
      walled carbon nanotubes (SWNTs) and poly(sodium 4-styrenesulfonate) (PSS)
      utilizing the electrostatic interaction. Spectroscopic results indicated that ILs
      did not affect the conformation of the enzyme. The cyclic voltammetric results
      showed that the electrocatalytic activity of the GOx-IL-PSS-SWNTs/GC electrode
      was lower than that of the GOx-SWNTs/GC electrode. The characteristic kinetic
      constants of the enzymatic reaction were evaluated from the cyclic voltammograms
      under a substrate-saturated condition. The values of the characteristic rate
      constant obtained at each IL-containing enzyme electrode were lower than those
      obtained at the GOx-SWNTs/GC electrode and decreased following the sequence of
      SWNTs > [bmpyri] > [bmpyrro] > [bmim]. The theoretical calculations combined with
      experiments were employed to address the interaction between the ILs and SWNTs,
      showing that the presence of IL on the surface of SWNTs could significantly
      affect the electrical transfer properties of the nanotube and led to the decrease
      of the electrocatalytic activity of the GOx-IL-PSS-SWNTs/GC electrode. These
      results indicate that the nature of ILs is the main factor, which affects the
      electrocatalytic activity of the GOx-IL-PSS-SWNTs/GC electrodes toward the
      oxidation of glucose. The results of this study are directly relevant for those
      applications where ILs are employed in the form of thin films supported on solid
      surfaces, such as the designing of the related biosensor, microelectronic devices
      in the ILs-containing system, and so forth.

PMID- 19746959
TI  - Effects of core distances, solvent, ligand, and level of theory on the TDDFT
      optical absorption spectrum of the thiolate-protected Au(25) nanoparticle.
AB  - Density functional theory calculations are employed to calculate geometries (R =
      H, CH(3), CH(2)CH(3), CH(2)CH(2)Ph) and excitation energies (R = H, CH(3),
      CH(2)CH(3)) for the Au(25)(SR)(18)(-) nanoparticle. The splitting between the
      first two peaks in the optical absorption spectrum is known to arise as a result
      of ligand-field splitting of superatom D orbitals, and the value of this
      splitting is found to be a very sensitive probe of gold-gold distances in the
      Au(25)(SH)(18)(-) nanoparticle core. LDA functionals such as Xalpha with a triple
      zeta basis set are found to predict core geometries in good agreement with
      experiment, which suggests that this level of theory may be useful in future
      structural predictions. Asymptotically correct potentials SAOP and LB94 with
      triple-zeta basis sets yield excitation energies within 0.15-0.20 eV of
      experimental values; LB94 with a frozen-core basis set is found to be an
      inexpensive alternative to the preferred SAOP potential. The size of the ligand
      plays a minor role on the optical absorption spectrum and solvent effects on
      geometries and excitation energies are negligible, which demonstrates that the
      core geometric and electronic structure is primarily responsible for the discrete
      optical absorption exhibited by this nanoparticle.

PMID- 19746960
TI  - Solvent control of the soft angular potential in hydroxyl-pi hydrogen bonds:
      inertial orientational dynamics.
AB  - Ultrafast polarization and wavelength selective IR pump-probe spectroscopy is
      used to measure the inertial and long time orientational dynamics of pi-hydrogen
      bonding complexes. Inertial orientational relaxation is sensitive to the angular
      potential associated with the hydrogen bond. The complexes studied are composed
      of phenol-OD (hydroxyl hydrogen replaced by deuterium) and various pi-base
      solvents with different electron donating or withdrawing substituents
      (chlorobenzene, bromobenzene, benzene, toluene, p-xylene, mesitylene, 1-pentyne).
      The different substituents provide experimental control of the hydrogen bond
      strength. The inertial orientational relaxation of the complexes, measured at the
      center frequency of each line, is independent of the hydrogen bond strength,
      demonstrating the insensitivity of the OD inertial dynamics, and therefore the H
      bond angular potential, to the hydrogen bond strength. OD stretch absorption
      bands are inhomogeneously broadened through interactions with the solvent. The
      hydrogen bonding complexes all have similar wavelength dependent inertial
      orientational relaxation across their inhomogeneously broadened OD stretch
      absorption lines. The wavelength dependence of the inertial reorientation across
      each line arises because of a correlation between local solvent structure and the
      angular potential. These two results imply that local solvent structure acts as
      the controlling influence in determining the extent of inertial orientational
      relaxation, and therefore the angular potential, and that variation in the pi
      hydrogen bond strength is of secondary importance.

PMID- 19746961
TI  - Silicon nanotube battery anodes.
AB  - We present Si nanotubes prepared by reductive decomposition of a silicon
      precursor in an alumina template and etching. These nanotubes show impressive
      results, which shows very high reversible charge capacity of 3247 mA h/g with
      Coulombic efficiency of 89%, and also demonstrate superior capacity retention
      even at 5C rate (=15 A/g). Furthermore, the capacity in a Li-ion full cell
      consisting of a cathode of LiCoO2 and anode of Si nanotubes demonstrates a 10
      times higher capacity than commercially available graphite even after 200 cycles.

PMID- 19746962
TI  - An ab initio/rice--Ramsperger--Kassel--Marcus study of the reactions of propenols
      with OH. Mechanism and kinetics of H abstraction channels.
AB  - Propenols have been found to be common intermediates in the hydrocarbon
      combustion and they are present in substantial concentrations in a wide range of
      flames. However, the kinetics properties of these species in combustion flames
      have not received much attention. In this work, the mechanism and kinetics of the
      OH hydrogen abstraction from propenols are investigated. Three stable
      conformations of propenols, (E)-1-propenol, (Z)-1-propenol, and syn-propen-2-ol,
      are taken into consideration. The potential energy profiles for the three
      reaction systems have been first investigated by the CCSD(T) method. The
      geometric parameters and relative energies of the reactants, reactant complexes,
      transition states, product complexes, and products have been investigated
      theoretically. The rate constants are calculated in the temperature range of 200
      3000 K by the Variflex code based on the weak collision master
      equation/microcanonical variational RRKM theory. For all considered reactions,
      our results support a stepwise mechanism involving the formation of a reactant
      complex in the entrance channel and a product complex in the exit channel. In the
      reaction of OH with (E)-1-propenol, the hydrogen abstractions from the -CH(3) and
      -OH sites are dominant and competitive with each other in the temperature range
      from 500 to 2000 K. Above 2000 K, the hydrogen abstraction from the -CH group
      bonded to O atom becomes dominant with a relative yield of 51.1% at 3000 K. In
      the reaction of OH with (Z)-1-propenol, the hydrogen abstractions from -CH(3), 
      CH bonded to O atom, and -OH are preferable in the temperature range from 500 to
      1800 K, with the first two channels being competitive with each other. Above 1800
      K, the hydrogen abstraction reaction from the CH group bonded to the CH(3) group
      becomes dominant with the branching ratio of 90.3% at 3000 K. In the reaction of
      OH with syn-propen-2-ol, the abstractions from the -CH(3) and -OH sites are
      competitive with each other when the temperature is higher than 500 K, and they
      become dominant above 800 K with the relative yields of 70.5% and 29.5% at 3000
      K, respectively. The predicted total rate constants at the pressure of 1 atm
      fitted by modified three-parameter Arrhenius expressions in two different
      temperature ranges are also provided.

PMID- 19746963
TI  - Design, synthesis, protein-ligand X-ray structure, and biological evaluation of a
      series of novel macrocyclic human immunodeficiency virus-1 protease inhibitors to
      combat drug resistance.
AB  - The structure-based design, synthesis, and biological evaluation of a series of
      nonpeptidic macrocyclic HIV protease inhibitors are described. The inhibitors are
      designed to effectively fill in the hydrophobic pocket in the S1'-S2' subsites
      and retain all major hydrogen bonding interactions with the protein backbone
      similar to darunavir (1) or inhibitor 2. The ring size, the effect of methyl
      substitution, and unsaturation within the macrocyclic ring structure were
      assessed. In general, cyclic inhibitors were significantly more potent than their
      acyclic homologues, saturated rings were less active than their unsaturated
      analogues and a preference for 10- and 13-membered macrocylic rings was revealed.
      The addition of methyl substituents resulted in a reduction of potency. Both
      inhibitors 14b and 14c exhibited marked enzyme inhibitory and antiviral activity,
      and they exerted potent activity against multidrug-resistant HIV-1 variants.
      Protein-ligand X-ray structures of inhibitors 2 and 14c provided critical
      molecular insights into the ligand-binding site interactions.

PMID- 19746965
TI  - An Fe2+-dependent cyclic phosphodiesterase catalyzes the hydrolysis of 7,8
      dihydro-D-neopterin 2',3'-cyclic phosphate in methanopterin biosynthesis.
AB  - 7,8-Dihydro-D-neopterin 2',3'-cyclic phosphate (H(2)N-cP) is the first
      intermediate in biosynthesis of the pterin portion of tetrahydromethanopterin
      (H(4)MPT), a C(1) carrier coenzyme first identified in the methanogenic archaea.
      This intermediate is produced from GTP by MptA (MJ0775 gene product), a new class
      of GTP cyclohydrolase I [Grochowski, L. L., Xu, H., Leung, K., and White, R. H.
      (2007) Biochemistry 46, 6658-6667]. Here we report the identification of a cyclic
      phosphodiesterase that hydrolyzes the cyclic phosphate of H(2)N-cP and converts
      it to a mixture of 7,8-dihydro-D-neopterin 2'-monophosphate and 7,8-dihydro-d
      neopterin 3'-monophosphate. The enzyme from Methanocaldococcus jannachii is
      designated MptB (MJ0837 gene product) to indicate that it catalyzes the second
      step of the biosynthesis of methanopterin. MptB is a member of the HD domain
      superfamily of enzymes, which require divalent metals for activity. Direct metal
      analysis of the recombinant enzyme demonstrated that MptB contained 1.0 mol of
      zinc and 0.8 mol of iron per protomer. MptB requires Fe(2+) for activity, the
      same as observed for MptA. Thus the first two enzymes involved in H(4)MPT
      biosynthesis in the archaea are Fe(2+) dependent.

PMID- 19746964
TI  - Osteogenic differentiation of human mesenchymal stem cells directed by
      extracellular matrix-mimicking ligands in a biomimetic self-assembled peptide
      amphiphile nanomatrix.
AB  - This study investigated the ability of nanoscale, biomimetic peptide amphiphile
      (PA) scaffolds inscribed with specific cellular adhesive ligands to direct the
      osteogenic differentiation of human mesenchymal stem cells (hMSCs) without
      osteogenic supplements. PA sequences were synthesized to mimic the native bone
      extracellular matrix (ECM), expressing different isolated ligands (i.e., RGDS,
      DGEA, KRSR). All PAs were presented as self-assembled two-dimensional coatings
      for the seeded hMSCs. Initial attachment results demonstrated that the different
      PAs could be individually recognized based on the incorporated adhesive ligands.
      Long-term studies assessed osteogenic differentiation up to 35 days. The RGDS
      containing PA nanomatrix expressed significantly greater alkaline phosphatase
      activity, indicating the early promotion of osteogenic differentiation. A
      progressive shift toward osteogenic morphology and positive staining for mineral
      deposition provided further confirmation of the RGDS-containing PA nanomatrix.
      Overall, the PA nanomatrix clearly has great promise for directing the osteogenic
      differentiation of hMSCs without the aid of supplements by mimicking the native
      ECM, providing an adaptable environment that allows for different adhesive
      ligands to control cellular behaviors. This research model establishes the
      beginnings of a new versatile approach to regenerate bone tissues by closely
      following the principles of natural tissue formation.

PMID- 19746966
TI  - Arginine, a key residue for the enhancing ability of an antifreeze protein of the
      beetle Dendroides canadensis.
AB  - Antifreeze proteins (AFPs) can produce a difference between the nonequilibrium
      freezing point and the melting point, termed thermal hysteresis (TH). The TH
      activity of an antifreeze protein (AFP) depends on the specific AFP and its
      concentration as well as the presence of cosolutes including low molecular mass
      solutes and/or proteins. We recently identified series of carboxylates and
      polyols as efficient enhancers for an AFP from the beetle Dendroides canadensis.
      In this study, we chemically modified DAFP-1 using the arginine-specific reagent
      1,2-cyclohexanedione. We demonstrated that 1,2-cyclohexanedione specifically
      modifies one arginine residue and the modified DAFP-1 loses its enhancing ability
      completely or partially in the presence of previously identified enhancers. The
      stronger the enhancement ability of the enhancer on the native DAFP-1, the
      stronger the enhancement effect of the enhancer on the modified DAFP-1. The
      weaker enhancers (e.g., glycerol) completely lose their enhancement effect on the
      modified DAFP-1 due to their inability to compete with 1,2-cyclohexanedione for
      the arginine residue. Regeneration of the arginine residue using hydroxylamine
      fully restored the enhancing ability of DAFP-1. These studies indicated that an
      arginine residue is critical for the enhancing ability of DAFP-1 and the
      guanidinium group of the arginine residue is important for its interaction with
      the enhancers, where the general mechanism of arginine-ligand interaction is
      borne. This work may initiate a complete mechanistic study of the enhancement
      effect in AFPs.

PMID- 19746967
TI  - Photo-cross-linked hydrogels from thermoresponsive PEGMEMA-PPGMA-EGDMA copolymers
      containing multiple methacrylate groups: mechanical property, swelling, protein
      release, and cytotoxicity.
AB  - Photo-cross-linked hydrogels from thermoresponsive polymers can be used as
      advanced injectable biomaterials via a combination of physical interaction (in
      situ thermal gelation) and covalent cross-links (in situ photopolymerization).
      This can lead to gels with significantly enhanced mechanical properties compared
      to non-photo-cross-linked thermoresponsive hydrogels. Moreover, the thermally
      phase-separated gels have attractive advantages over non-thermoresponsive gels
      because thermal gelation upon injection allows easy handling and holds the shape
      of the gels prior to photopolymerization. In this study, water-soluble
      thermoresponsive copolymers containing multiple methacrylate groups were
      synthesized via one-step deactivation enhanced atom transfer radical
      polymerization (ATRP) of poly(ethylene glycol) methyl ether methacrylate
      (PEGMEMA, M(n) = 475), poly(propylene glycol) methacrylate (PPGMA, M(n) = 375),
      and ethylene glycol dimethacrylate (EGDMA) and were used to form covalent cross
      linked hydrogels by photopolymerization. The cross-linking density was found to
      have a significant influence on the mechanical and swelling properties of the
      photo-cross-linked gels. Release studies using lysozyme as a model protein
      demonstrated a sustained release profile that varied dependent on the copolymer
      composition, cross-linking density, and the temperature. Mouse C2C12 myoblast
      cells were cultured in the presence of the copolymers at concentrations up to 1
      mg/mL. It was found that the majority of the cells remained viable, as assessed
      by Alamar Blue, lactate dehydrogenase (LDH), and Live/Dead cell
      viability/cytotoxicity assays. These studies demonstrate that thermoresponsive
      PEGMEMA-PPGMA-EGDMA copolymers offer potential as in situ photopolymerizable
      materials for tissue engineering and drug delivery applications through a
      combination of facile synthesis, enhanced mechanical properties, tunable cross
      linking density, low cytotoxicity, and accessible functionality for further
      structure modifications.

PMID- 19746969
TI  - Kinetics and thermodynamics of flip-flop in binary phospholipid membranes
      measured by sum-frequency vibrational spectroscopy.
AB  - In order to better characterize the dependence of lipid flip-flop rate and
      thermodynamics on the nature of the lipid headgroup, we have studied the kinetics
      of flip-flop for single-lipid and mixed-lipid bilayers consisting of 1,2
      distearoyl-sn-glycero-3-phosphocholine (DSPC) and 1,2-distearoyl-sn-glycero-3
      phosphoethanolamine (DSPE) as a function of both pressure and temperature. The
      kinetics of flipping were studied by sum-frequency vibrational spectroscopy
      (SFVS), which does not require exogenous chemical labeling of the lipid species
      of interest. Additionally, SFVS may be employed to track only a single species
      (DSPE or DSPC) within a binary mixture by selective deuteration of the matrix
      lipid to make it spectroscopically inactive. Using this approach, we have found
      the flip-flop of pure DSPE to be slower than the flip-flop of pure DSPC by nearly
      2 orders of magnitude. The thermodynamics of the pure systems were analyzed in
      order to better understand the physical factors underlying their transmembrane
      dynamics. Headgroup hydrophobicity and associated solvent effects, as well as
      lipid packing constraints, appear to play a key role in determining the rate of
      flip-flop for these two species. For mixtures of DSPE + DSPC, both components
      exhibited similar rates of flip-flop at a given mole fraction of DSPE. The
      kinetics and thermodynamics of flip-flop in the mixtures did not vary uniformly
      with changing composition but were well correlated to changes in the molecular
      packing as a function of DSPE content in the bilayer.

PMID- 19746968
TI  - Spectroscopic studies of the AppA BLUF domain from Rhodobacter sphaeroides:
      addressing movement of tryptophan 104 in the signaling state.
AB  - Previous crystallographic studies of the AppA BLUF domain indicated that Trp104
      is capable of undertaking alternate conformations depending on the length of the
      BLUF domain. A BLUF domain containing a C-terminal deletion (AppA1-126) reveals
      that Trp104 is partially solvent exposed while a BLUF domain containing a
      slightly longer carboxyl terminal region (AppA17-133) shows that Trp104 is deeply
      buried. This observation has led to a model proposing that Trp104 moves from a
      deeply buried position in the dark state to a solvent-exposed position in the
      light excited state. In this study we investigated whether there is indeed
      movement of Trp104 upon light excitation using a combination of NMR and
      absorption spectroscopy, steady-state fluorescence, and acrylamide quenching of
      tryptophan fluorescence. Our results indicate that AppA17-133 and AppA1-126
      contain Trp104 in distinct alternate conformations in solution and that light
      absorption by the flavin causes partial movement/uncovering of Trp104. However,
      we conclude that light exposure does not cause dramatic change of Trp104 from
      "Trp-in" to "Trp-out" conformations (or vice versa) upon light absorption. These
      results do not support a model of Trp104 movement as a key output signal.

PMID- 19746970
TI  - Significance of nonstatistical dynamics in organic reaction mechanisms: time
      dependent stereoselectivity in cyclopentyne-alkene cycloadditions.
AB  - The stereochemistry of the reaction between cyclopentyne and ethene has been
      modeled using statistical methods, based on RRKM theory and a master equation
      analysis, and by molecular dynamics. We show that the stereochemical retention
      observed experimentally is not compatible with statistical models that invoke a
      diradical mechanism but that it can be rationalized through analysis of short
      time diradical dynamics. Within the first approximately 400 fs, reaction occurs
      from the initial diradical adduct to form a carbene, which may subsequently
      isomerize to give the final product. The carbene route has a significantly higher
      barrier than other channels; however, at short times the reaction energy is
      efficiently coupled into the reaction coordinate for carbene formation. Loss of
      the initial ethene stereochemistry by rotation about the former C=C bond occurs
      on a time scale of approximately 300 fs, so that stereochemistry is retained in
      the carbene on short time scales. The bond rotation required to pass directly
      through the low energy transition state leading from the diradical to the [2+2]
      cycloaddition product is slow because of the attached heavy groups, occurring on
      a 1-2 ps time scale. Therefore, this low energy channel only becomes active on
      longer time scales, when memory of the initial ethene stereochemistry has been
      lost. Short time retention of stereochemistry via the carbene is thus related to
      the time scales for randomization of both the energy and the geometry. It is
      argued that these effects may combine to amplify the stereochemical retention for
      reaction of substituted ethenes in solution.

PMID- 19746971
TI  - Dyotropic reactions: mechanisms and synthetic applications.

PMID- 19746972
TI  - Dissipation in films of adsorbed nanospheres studied by quartz crystal
      microbalance (QCM).
AB  - The quartz crystal microbalance (QCM) has become a popular method to study the
      formation of surface-confined films that consist of discrete biomolecular objects
      -such as proteins, phospholipid vesicles, virus particles--in liquids. The
      quantitative interpretation of QCM data--frequency and bandwidth (or,
      equivalently, dissipation) shifts--obtained with such films is limited by the
      lack of understanding of the energy dissipation mechanisms that operate in these
      films as they are sheared at megahertz frequencies during the QCM experiment.
      Here, we investigate dissipation mechanisms in such films experimentally and by
      finite-element method (FEM) calculations. Experimentally, we study the adsorption
      of globular proteins and virus particles to surfaces with various attachment
      geometries: direct adsorption to the surface, attachment via multiple anchors, or
      attachment via a single anchor. We find that the extent of dissipation caused by
      the film and the evolution of dissipation as a function of surface coverage is
      not dependent on the internal properties of these particles but rather on the
      geometry of their attachment to the surface. FEM calculations reproduce the
      experimentally observed behavior of the dissipation. In particular, a transient
      maximum in dissipation that is observed experimentally is reproduced by the FEM
      calculations, provided that the contact zone between the sphere and the surface
      is narrow and sufficiently soft. Both a small-angle rotation of the sphere in the
      flow field of the background fluid (rocking) and a small-amplitude slippage
      (sliding) contribute to the dissipation. At high coverage, lateral hydrodynamic
      interactions between neighboring spheres counteract these modes of dissipation,
      which results in a maximum in dissipation at intermediate adsorption times. These
      results highlight that, in many scenarios of biomolecular adsorption, the
      dissipation is not primarily determined by the adsorbate itself, but rather by
      the link by which it is bound to the substrate.

PMID- 19746973
TI  - Base-promoted ammonia borane hydrogen-release.
AB  - The strong non-nucleophilic base bis(dimethylamino)naphthalene (Proton Sponge,
      PS) has been found to promote the rate and extent of H(2)-release from ammonia
      borane (AB) either in the solid state or in ionic-liquid and tetraglyme
      solutions. For example, AB reactions in 1-butyl-3-methylimidazolium chloride
      (bmimCl) containing 5.3 mol % PS released 2 equiv of H(2) in 171 min at 85
      degrees C and only 9 min at 110 degrees C, whereas comparable reactions without
      PS required 316 min at 85 degrees C and 20 min at 110 degrees C. Ionic-liquid
      solvents proved more favorable than tetraglyme since they reduced the formation
      of undesirable products such as borazine. Solid-state and solution (11)B NMR
      studies of PS-promoted reactions in progress support a reaction pathway involving
      initial AB deprotonation to form the H(3)BNH(2)(-) anion. This anion can then
      initiate AB dehydropolymerization to form branched-chain polyaminoborane
      polymers. Subsequent chain-branching and dehydrogenation reactions lead
      ultimately to a cross-linked polyborazylene-type product. AB dehydrogenation by
      lithium and potassium triethylborohydride was found to produce the stabilized
      Et(3)BNH(2)BH(3)(-) anion, with the crystallographically determined structure of
      the [Et(3)BNH(2)BH(3)](-)K(+).18-crown-6 complex showing that, following AB
      nitrogen-deprotonation by the triethylborohydride, the Lewis-acidic
      triethylborane group coordinated at the nitrogen. Model studies of the reactions
      of [Et(3)BNH(2)BH(3)](-)Li(+) with AB show evidence of chain-growth, providing
      additional support for a PS-promoted AB anionic dehydropolymerization H(2)
      release process.

PMID- 19746974
TI  - Palladium-catalyzed alkenylation of quinoline-N-oxides via C-H activation under
      external-oxidant-free conditions.
AB  - The direct cross-coupling of quinoline-N-oxides with olefin derivatives has been
      realized using palladium acetate as the catalyst in the absence of external
      ligand and oxidant to give the corresponding 2-alkenylated quinolines and 1
      alkenylated isoquinolines chemo- and regioselectively in 27-95% yield. The
      catalytic process is proposed to proceed via direct C-H bond activation of the
      quinoline-N-oxide with Pd(OAc)(2) followed by Heck coupling with the olefin. The
      resultant N-oxide of the alkenylated quinoline can oxidize the reduced Pd(0) to
      regenerate the Pd(II) active species and simultaneously release the 2-alkenylated
      quinoline without using any external oxidants and reductants.

PMID- 19746975
TI  - Structure-based optimization of arylamides as inhibitors of soluble epoxide
      hydrolase.
AB  - Inhibition of soluble epoxide hydrolase (sEH) is hypothesized to lead to an
      increase in circulating levels of epoxyeicosatrienoic acids, resulting in the
      potentiation of their in vivo pharmacological properties. As part of an effort to
      identify inhibitors of sEH with high and sustained plasma exposure, we recently
      performed a high throughput screen of our compound collection. The screen
      identified N-(3,3-diphenyl-propyl)-nicotinamide as a potent inhibitor of sEH.
      Further profiling of this lead revealed short metabolic half-lives in microsomes
      and rapid clearance in the rat. Consistent with these observations, the
      determination of the in vitro metabolic profile of N-(3,3-diphenyl-propyl)
      nicotinamide in rat liver microsomes revealed extensive oxidative metabolism and
      a propensity for metabolite switching. Lead optimization, guided by the analysis
      of the solid-state costructure of N-(3,3-diphenyl-propyl)-nicotinamide bound to
      human sEH, led to the identification of a class of potent and selective
      inhibitors. An inhibitor from this class displayed an attractive in vitro
      metabolic profile and high and sustained plasma exposure in the rat after oral
      administration.

PMID- 19746977
TI  - Mechanistic studies on the formation of linear polyethylene chain catalyzed by
      palladium phosphine-sulfonate complexes: experiment and theoretical studies.
AB  - Linear polyethylene propagation starting from Pd phosphine-sulfonate complexes,
      Pd(CH(3))(L)(Ar(2)PC(6)H(4)SO(3)) (L = 2,6-lutidine, Ar = o-MeOC(6)H(4) (2a) and
      L = pyridine, Ar = Ph (2b)), was studied both experimentally and theoretically.
      Experimentally, highly linear polyethylene was obtained with
      Pd(CH(3))(L)(Ar(2)PC(6)H(4)SO(3)) complexes 2a and 2b. Formation of a long alkyl
      substituted palladium complex (3) was detected as a result of ethylene
      oligomerization on a palladium center starting from methylpalladium complex.
      Additionally, well-defined ethyl and propyl complexes (6(Et) and 6(Pr)) were
      synthesized as stable n-alkyl palladium complexes. In spite of the existence of
      beta-hydrogens, the beta-hydride elimination to give 1-alkenes was very slow or
      negligible in all cases. On the other hand, isomerization of 1-hexene in the
      presence of a methylpalladium/phosphine-sulfonate complex 2a indicated that this
      catalyst system actually undergoes beta-hydride elimination and reinsertion to
      release internal alkenes. On the theoretical side, the relative energies were
      calculated for intermediates and transition states for chain-growth, chain
      walking, and chain-transfer on the basis of the starting model complex Pd(n
      C(3)H(7))(pyridine)(o-Me(2)PC(6)H(4)SO(3)) (8). First, cis/trans isomerization
      process via the Berry's pseudorotation was proposed for the Pd/phosphine
      sulfonate system. The second oxygen atom of sulfonate group is involved in the
      isomerization process as the associative ligand, which is one of the most unique
      natures of the sulfonate group. Chain propagation was suggested to take place
      from the less stable alkylPd(ethylene) complex 10' with the TS of 27.4/27.7
      ((E+ZPC)/G) kcal/mol. Possible beta-hydride elimination was suggested to occur
      under low concentration of ethylene: the highest-energy transition state to
      override for beta-hydride elimination was either >37.4/25.3 kcal/mol (TS(9-12))
      or 29.1/27.4 kcal/mol (TS(8'-9') to reach 12'). The ethylene insertion to the iso
      alkylpalladium species (14') is allowed via a TS of 28.6/29.1 kcal/mol (TS(14'
      15')), slightly higher in energy than that for the normal-alkylpalladium species
      (TS(10'-11')). Easy chain transfer was suggested to proceed from the more stable
      PdH(olefin) complex 12' if beta-hydride elimination to 12' does take place. Thus,
      the production of linear polyethylene with high molecular weight under ethylene
      pressure suggests that the cis and trans PdH(alkene)(phosphine-sulfonate)
      complexes (12 and 12') are merely accessible in the presence of excess amount of
      ethylene.

PMID- 19746976
TI  - Function-oriented biosynthesis of beta-lactone proteasome inhibitors in
      Salinispora tropica.
AB  - The natural proteasome inhibitor salinosporamide A from the marine bacterium
      Salinispora tropica is a promising drug candidate for the treatment of multiple
      myeloma and mantle cell lymphoma. Using a comprehensive approach that combined
      chemical synthesis with metabolic engineering, we generated a series of
      salinosporamide analogues with altered proteasome binding affinity. One of the
      engineered compounds is equipotent to salinosporamide A in inhibition of the
      chymotrypsin-like activity of the proteasome yet exhibits superior activity in
      the cell-based HCT-116 assay.

PMID- 19746978
TI  - Investigation of functionally liver selective glucokinase activators for the
      treatment of type 2 diabetes.
AB  - Type 2 diabetes is a polygenic disease which afflicts nearly 200 million people
      worldwide and is expected to increase to near epidemic levels over the next 10-15
      years. Glucokinase (GK) activators are currently under investigation by a number
      of pharmaceutical companies with only a few reaching early clinical evaluation. A
      GK activator has the promise of potentially affecting both the beta-cells of the
      pancreas, by improving glucose sensitive insulin secretion, as well as the liver,
      by reducing uncontrolled glucose output and restoring post-prandial glucose
      uptake and storage as glycogen. Herein, we report our efforts on a sulfonamide
      chemotype with the aim to generate liver selective GK activators which culminated
      in the discovery of 3-cyclopentyl-N-(5-methoxy-thiazolo[5,4-b]pyridin-2-yl)-2-[4
      (4-methyl-piperazine-1-sulfonyl)-phenyl]-propionamide (17c). This compound
      activated the GK enzyme (alphaK(a) = 39 nM) in vitro at low nanomolar
      concentrations and significantly reduced glucose levels during an oral glucose
      tolerance test in normal mice.

PMID- 19746979
TI  - Allosteric functional switch of neurokinin A-mediated signaling at the neurokinin
      NK2 receptor: structural exploration.
AB  - The neurokinin NK2 receptor is known to pre-exist in equilibrium between at least
      three states: resting-inactive, calcium-triggering, and cAMP-producing. Its
      endogeneous ligand, NKA, mainly induces the calcium response. Using a FRET-based
      assay, we have previously discovered an allosteric modulator of the NK2 receptor
      that has the unique ability to discriminate among the two signaling pathways:
      calcium-signaling is not affected while cAMP signaling is significantly
      decreased. A series of compounds have been prepared and studied in order to
      better understand the structural determinants of this allosteric functional
      switch of a GPCR. Most of them display the same allosteric profile, with smooth
      pharmacomodulation. One compound however exhibits significantly improved
      modulatory properties of NKA induced signaling when compared to the original
      modulator.

PMID- 19746980
TI  - Biochemical and functional characterization of a metalloprotease from the
      thermophilic fungus Thermoascus aurantiacus.
AB  - Protease production was carried out in solid state fermentation. The enzyme was
      purified through precipitation with ethanol at 72% followed by chromatographies
      in columns of Sephadex G75 and Sephacryl S100. It was purified 80-fold and
      exhibited recovery of total activity of 0.4%. SDS-PAGE analysis indicated an
      estimated molecular mass of 24.5 kDa and the N-terminal sequence of the first 22
      residues was APYSGYQCSMQLCLTCALMNCA. Purified protease was only inhibited by EDTA
      (96.7%) and stimulated by Fe(2+) revealing to be a metalloprotease activated by
      iron. Optimum pH was 5.5, optimum temperature was 75 degrees C, and it was
      thermostable at 65 degrees C for 1 h maintaining more than 70% of original
      activity. Through enzyme kinetic studies, protease better hydrolyzed casein than
      azocasein. The screening of fluorescence resonance energy transfer (FRET) peptide
      series derived from Abz-KLXSSKQ-EDDnp revealed that the enzyme exhibited
      preference for Arg in P(1) (k(cat)/K(m) = 30.1 mM(-1) s(-1)).

PMID- 19746981
TI  - Multiresponsive supramolecular nanogated ensembles.
AB  - A new multiresponsive supramolecular nanogated ensemble has been developed by
      introducing beta-cyclodextrin (beta-CD) into polymer-grafted mesoporous silica.
      The cross-linked polymer produced by host-guest interaction between beta-CD and
      diazo-linker works as a gatekeeper to control the release of trapped molecules
      from hybrid materials. The presence of UV light, alpha-CD, or disulfide reducing
      agent can effectively open the polymeric network and release the loading with
      different dynamics.

PMID- 19746982
TI  - Multiphase transformations controlled by ostwald's rule in nanostructured
      Ce(0.5)Zr(0.5)O(2) powders prepared by a modified Pechini route.
AB  - The thermal stability of nanostructured Ce(0.5)Zr(0.5)O(2) powders prepared by
      the Pechini method was studied on the nanometric scale by X-ray diffraction
      (XRD), energy-dispersive spectrometry (EDS), transmission electron microscopy
      (TEM), nuclear magnetic resonance (NMR), and Raman techniques. Obtained results
      demonstrate that amorphous powders coming from the thermal decomposition of the
      precursor transform into the stable crystalline state through one highly
      disordered and metastable intermediate. This is a new example of successive
      reactions controlled by Ostwald's rule in inorganic systems. At low calcination
      temperatures, the combination of Raman spectroscopy, high-resolution electron
      microscopy, and EDS nanoanalysis showed the formation from the precursor powder
      of a disordered pseudocubic phase. At 900 degrees C, metastable T' and stable T
      and C phases were detected in XRD patterns. As increasing temperature,
      crystallites growth and proportions of stable T and C phases increased at the
      expense of the T' phase, which completely disappeared at 1300 degrees C. In
      analyzed samples, the Raman technique and (crystal by crystal) EDS nanoanalyses
      were used to detect local phase inhomogeneity. Compositions and relative
      percentages of phases were investigated by XRD Rietveld analysis and discussed in
      terms of phase diagrams previously reported.

PMID- 19746983
TI  - Design, synthesis, and structure-activity relationship of a novel series of 2
      aryl 5-(4-oxo-3-phenethyl-2-thioxothiazolidinylidenemethyl)furans as HIV-1 entry
      inhibitors.
AB  - We previously identified two small molecules targeting the HIV-1 gp41, N-(4
      carboxy-3-hydroxy)phenyl-2,5-dimethylpyrrole 12 (NB-2) and N-(3-carboxy-4
      chloro)phenylpyrrole 13 (NB-64), that inhibit HIV-1 infection at low micromolar
      levels. On the basis of molecular docking analysis, we designed a series of 2
      aryl 5-(4-oxo-3-phenethyl-2-thioxothiazolidinylidenemethyl)furans. Compared with
      12 and 13, these compounds have bigger molecular size (437-515 Da) and could
      occupy more space in the deep hydrophobic pocket on the gp41 NHR trimer. Fifteen
      2-aryl 5-(4-oxo-3-phenethyl-2-thioxothiazolidinylidenemethyl)furans (11a-o) were
      synthesized by Suzuki-Miyaura cross-coupling followed by a Knoevenagel
      condensation and tested for their anti-HIV-1 activity and cytotoxicity on MT-2
      cells. We found that all 15 compounds had improved anti-HIV-1 activity and 3 of
      them (11a, 11b, and 11d) exhibited inhibitory activity against replication of HIV
      1(IIIB) and 94UG103 at <100 nM range, more than 20-fold more potent than 12 and
      13, suggesting that these compounds can serve as leads for development of novel
      small molecule HIV fusion inhibitors.

PMID- 19746984
TI  - AAA-DDD triple hydrogen bond complexes.
AB  - Experiment and theory both suggest that the AAA-DDD pattern of hydrogen bond
      acceptors (A) and donors (D) is the arrangement of three contiguous hydrogen
      bonding centers that results in the strongest association between two species.
      Murray and Zimmerman prepared the first example of such a system (complex 3*2)
      and determined the lower limit of its association constant (K(a)) in CDCl(3) to
      be 10(5) M(-1) by (1)H NMR spectroscopy (Murray, T. J. and Zimmerman, S. C. J.
      Am. Chem. Soc. 1992, 114, 4010-4011). The first cationic AAA-DDD pair (3*4(+))
      was described by Bell and Anslyn (Bell, D. A. and Anslyn, E. A. Tetrahedron 1995,
      51, 7161-7172), with a K(a) > 5 x 10(5) M(-1) in CH(2)Cl(2) as determined by UV
      vis spectroscopy. We were recently able to quantify the strength of a neutral AAA
      DDD arrangement using a more chemically stable AAA-DDD system, 6*2, which has an
      association constant of 2 x 10(7) M(-1) in CH(2)Cl(2) (Djurdjevic, S., Leigh, D.
      A., McNab, H., Parsons, S., Teobaldi, G. and Zerbetto, F. J. Am. Chem. Soc. 2007,
      129, 476-477). Here we report on further AA(A) and DDD partners, together with
      the first precise measurement of the association constant of a cationic AAA-DDD
      species. Complex 6*10(+)[B(3,5-(CF(3))(2)C(6)H(3))(4)(-)] has a K(a) = 3 x 10(10)
      M(-1) at RT in CH(2)Cl(2), by far the most strongly bound triple hydrogen bonded
      system measured to date. The X-ray crystal structure of 6*10(+) with a BPh(4)(-)
      counteranion shows a planar array of three short (NH...N distances 1.95-2.15 A),
      parallel (but staggered rather than strictly linear; N-H...N angles 165.4-168.8
      degrees), primary hydrogen bonds. These are apparently reinforced, as theory
      predicts, by close electrostatic interactions (NH-*-N distances 2.78-3.29 A)
      between each proton and the acceptor atoms of the adjacent primary hydrogen
      bonds.

PMID- 19746985
TI  - Synthesis and characterization of luminescent rhenium(I) tricarbonyl diimine
      complexes with a triarylboron moiety and the study of their fluoride ion-binding
      properties.
AB  - A series of alkynylrhenium(I) tricarbonyl diimine complexes with a triarylboron
      moiety has been synthesized and characterized. The binding properties of the
      complex toward fluoride ions have been studied using electronic absorption and
      emission spectroscopy and were further supported by (19)F NMR binding
      experiments.

PMID- 19746986
TI  - Density functional study of the high-temperature oxidation of o-, m- and p-xylyl
      radicals.
AB  - Theoretical calculations at the CBS-QB3 level of theory have been performed to
      investigate the potential energy surface for the reaction of o-, m- and p-xylyl
      with molecular oxygen. The differences of the relative potential energies for the
      products and the transition states of o-, m- and p-xylyl with molecular oxygen
      were found to be within 8.5 kJ/mol at the CBS-QB3 level of theory. Although the
      reaction of m- and p-xylyl radicals with molecular oxygen have the same reaction
      pathways and also the same reaction thermochemistry as that of benzyl radicals,
      the o-xylylperoxy radicals formed by the reaction of o-xylyl + O(2) had an
      additional intramolecular isomerization pathway to form the o-xylyl hydroperoxy
      radicals. The rate constants and the product branching ratios for the o-xylyl +
      O(2) and its subsequent reactions were evaluated by the RRKM and master equation
      analysis. Possible roles for these reaction pathways on the combustion of o
      xylenes are discussed.

PMID- 19746987
TI  - N-terminal extension of beta B1-crystallin: identification of a critical region
      that modulates protein interaction with beta A3-crystallin.
AB  - The human lens proteins beta-crystallins are subdivided into acidic (betaA1
      betaA4) and basic (betaB1-betaB3) subunit groups. These structural proteins exist
      at extremely high concentrations and associate into oligomers under physiological
      conditions. Crystallin acidic-basic pairs tend to form strong heteromolecular
      associations. The long N-terminal extensions of beta-crystallins may influence
      both homo- and heteromolecular interactions. However, identification of the
      critical regions of the extensions mediating protein associations has not been
      previously addressed. This was studied by comparing the self-association and
      heteromolecular associations of wild-type recombinant betaA3- and betaB1
      crystallins and their N-terminally truncated counterparts (betaA3DeltaN30 and
      betaB1DeltaN56) using several biophysical techniques, including analytical
      ultracentrifugation and fluorescence spectroscopy. Removal of the N-terminal
      extension of betaA3 had no effect on dimerization or heteromolecular tetramer
      formation with betaB1. In contrast, the level of self-association of
      betaB1DeltaN56 increased, resulting in homotetramer formation, and
      heteromolecular association with betaA3 was blocked. Limited proteolysis of
      betaB1 produced betaB1DeltaN47, which is similar to intact protein formed dimers
      but in contrast showed enhanced heteromolecular tetramer formation with betaA3.
      The tryptic digestion was physiologically significant, corresponding to protease
      processing sites observed in vivo. Molecular modeling of the N-terminal betaB1
      extension indicates structural features that position a mobile loop in the
      vicinity of these processing sites. The loop is derived from residues 48-56 which
      appear to be critical for mediating protein interactions with betaA3-crystallin.

PMID- 19746988
TI  - Identification of emerging quasi-species in directed enzyme evolution.
AB  - The bases of enzyme evolution are structural changes in protein scaffolds
      combined with recognition and propagation of novel variants with valuable
      functional properties. Structural diversification may be accomplished by a
      variety of methods, including random mutations, homologous recombinations, and
      insertions and deletions of coding DNA sequences. The functional consequences of
      mutations are manifested at the protein level and are dependent on a substrate
      matrix, when catalytic properties are requested. Libraries of variant enzymes
      showing promiscuous activities can be interrogated with a set of alternative
      substrates. We demonstrate using a library of glutathione transferases (GSTs)
      that the functional properties are not uniformly distributed in substrate
      activity space but form clusters, or quasi-species. Multivariate analysis
      facilitates the identification of such quasi-species, which can be regarded as
      the proper developing units in molecular evolution.

PMID- 19746989
TI  - A tetranuclear Cu(I) cluster in the metallochaperone protein CopZ.
AB  - Copper trafficking proteins and copper-sensitive regulators are often found to be
      able to bind multiple Cu(I) ions in the form of Cu(I) clusters. We have
      determined the high-resolution X-ray crystal structure of an Atx1-like copper
      chaperone protein from Bacillus subtilis containing a novel tetranuclear Cu(I)
      cluster. The identities and oxidation states of the cluster ions were established
      unambiguously by refinement of X-ray energy-dependent anomalous scattering
      factors. The [Cu(4)(S-Cys)(4)(N-His)(2)] cluster geometry provides new structural
      insights into not only the binding of multiple cuprous ions by metallochaperones
      but also protein-associated tetranuclear Cu(I) clusters, including those found in
      eukaryotic copper-responsive transcription factors.

PMID- 19746990
TI  - Proteomics analysis reveals novel components in the detergent-insoluble
      subproteome in Alzheimer's disease.
AB  - Neurodegenerative diseases are often defined pathologically by the presence of
      protein aggregates. These aggregates, including amyloid plaques in Alzheimer's
      disease (AD), result from the abnormal accumulation and processing of proteins,
      and may ultimately lead to neuronal dysfunction and cell death. To date,
      conventional biochemical studies have revealed abundant core components in
      protein aggregates. However, rapidly improving proteomics technologies offer
      opportunities to revisit pathologic aggregate composition, and to identify less
      abundant but potentially important functional molecules that participate in
      neurodegeneration. The purpose of this study was to establish a proteomic
      strategy for the profiling of neurodegenerative disease tissues for disease
      specific changes in protein abundance. Using high resolution liquid
      chromatography coupled with tandem mass spectrometry (LC-MS/MS), we analyzed
      detergent-insoluble frontal cortex samples from AD and unaffected control cases.
      In addition, we analyzed samples from frontotemporal lobar degeneration (FTLD)
      cases to identify AD-specific changes not present in other neurodegenerative
      diseases. We used a labeling-free quantification technique to compare the
      abundance of identified peptides in the samples based on extracted ion current
      (XIC) of their corresponding ions. Of the 512 identified proteins, quantitation
      demonstrated significant changes in 81 AD-specific proteins. Following additional
      manual filtering, 11 proteins were accepted with high confidence as increased in
      AD compared to control and FTLD brains, including beta-amyloid, tau and
      apolipoprotein E, all well-established AD-linked proteins. In addition, we
      identified and validated the presence of serine protease 15, ankyrin B, and 14-3
      3 eta in the detergent-insoluble fraction. Our results provide further evidence
      for the capacity of proteomics applications to identify conserved sets of disease
      specific proteins in AD, to enhance our understanding of disease pathogenesis,
      and to deliver new candidates for the development of effective therapies for
      this, and other, devastating neurodegenerative disorders.

PMID- 19746991
TI  - Highly substituted indole library synthesis by palladium-catalyzed coupling
      reactions in solution and on a solid support.
AB  - 3-Iodoindoles have been synthesized by the iodocyclization of N,N-dialkyl-o-(1
      alkynyl)anilines, obtained by the Pd/Cu catalyzed coupling of terminal acetylenes
      with N,N-dialkyl-o-iodoanilines. These 3-iodoindoles undergo palladium-catalyzed
      Sonogashira and Suzuki coupling reactions to yield 1,2,3-trisubstituted indoles.
      These reactions have been applied to parallel library synthesis utilizing
      commercially available terminal acetylenes and boronic acids. The aforementioned
      chemistry has also been carried out on a chlorinated Wang resin as a solid
      support, affording 1,2,3,5-tetrasubstituted indoles after cleavage from the
      support. A diverse 42-member library of highly substituted indoles has been
      synthesized.

PMID- 19746992
TI  - Comparison of single- and multiobjective design of experiment in combinatorial
      chemistry for the selective dehydrogenation of propane.
AB  - Two genetic algorithms for the single- and multiobjective design of combinatorial
      experiments were applied to the optimization of a solid catalyst system active in
      the selective catalytic oxidation of propane to propylene. The two different
      optimization strategies, namely, the single objective optimization of the yield
      and the multiobjective optimization of the conversion and selectivity were
      implemented and compared. It was observed that the multiobjective approach
      optimized the yield in a similar way compared to the single objective approach.
      With respect to the selectivity, however, the multiobjective outperformed the
      single objective approach. It was also found that by applying the multiobjective
      optimization more interesting possible combinations were discovered.

PMID- 19746993
TI  - Efficient discovery of selective small molecule agonists of estrogen-related
      receptor gamma using combinatorial approach.
AB  - With the goal of discovering a selective agonist of estrogen-related receptor
      gamma (ERRgamma) with enhanced potency, we designed a series of small-molecule
      ligands derived from a known ERRgamma agonist, GSK4716, that can substantially
      potentiate the transcriptional activity of ERRgamma. Individual compounds among a
      30-member library of acyl hydrazones were pre-evaluated through in silico docking
      studies on the receptor cavities of ERRgamma LBDs using X-ray crystal structures
      cocrystallized with GSK4716 and 4-OHT. This rational approach to achieve the
      enhanced potency in ERRgamma transcriptional activity with selectivity over
      ERRalpha/beta enables us to complete the construction of a focused library by
      carrying out microwave-assisted parallel synthesis with excellent yields and
      purities. Finally, we identified a more potent ERRgamma agonist, E6, with
      excellent selectivity over ERRalpha/beta.

PMID- 19746994
TI  - Surface characteristics and adhesion behavior of Escherichia coli O157:H7: role
      of extracellular macromolecules.
AB  - Experiments were conducted using enterohemorrhagic Escherichia coli O157:H7 cells
      to investigate the influence of extracellular macromolecules on cell surface
      properties and adhesion behavior to quartz sand. Partial removal of the
      extracellular macromolecules on cells by a proteolytic enzyme (proteinase K) was
      confirmed using Fourier transform infrared spectroscopy analyses. The proteinase
      K treated cells exhibited more negative electrophoretic mobility (EPM) at an
      ionic strength (IS) < or = 1 mM, a slightly lower isoelectric point, and were
      less hydrophobic as compared to the untreated cells. Potentiometric titration
      results indicated that the total site concentration (i.e., the total amount of
      exposed functional groups per cell) on the treated cells was approximately 22%
      smaller than the untreated cells, while the dissociation constants were almost
      identical. Analysis of the EPM data using soft particle theory showed that the
      removal of extracellular macromolecules resulted in polymeric layers outside the
      cell surface that were less electrophoretically soft. The more negative mobility
      for the treated cells was likely due to the combined effects of a change in the
      distribution of functional groups and an increase in the charges per unit volume
      after enzyme treatment and not just removal of extracellular macromolecules. The
      proteolytic digestion of extracellular macromolecules led to a significant
      difference in the cell adhesion to quartz sand. The adhesion behavior for treated
      cells was consistent with DLVO theory and increased with IS due to less
      negativity in the EPM. In contrast, the adhesion behavior of untreated cells was
      much more complex and exhibited a maximum at IS = 1 mM. The treated cells
      exhibited less adhesion than the untreated cells when the IS < or = 1 mM due to
      their more negative EPM. However, when the IS > or = 10 mM, a sudden decrease in
      the removal efficiency was observed only for the untreated cells even through EPM
      values were similar for both treated and untreated cells. This result suggested
      that an additional non-DLVO type interaction, electrosteric repulsion, occurred
      at higher IS (> or =10 mM in this study) for the untreated cells due to the
      presence of extracellular macromolecules that hindered cell adhesion to the
      quartz surface. This finding provides important insight into the role of
      macromolecule-induced E. coli O157:H7 interactions in aquatic environments.

PMID- 19746995
TI  - Rapid, direct analysis of cholesterol by charge labeling in reactive desorption
      electrospray ionization.
AB  - Direct and rapid analysis of cholesterol was accomplished in the ambient
      environment using reactive desorption electrospray ionization (DESI) mass
      spectrometry. This was achieved by electrospraying reagent solutions in the form
      of high velocity charged droplets at surfaces such as dried serum samples and
      animal tissue sections. Betaine aldehyde, incorporated into the spray solvent,
      reacts selectively and rapidly with the alcohol group of cholesterol by
      nucleophilic addition, forming a hemiacetal salt. Limits of detection for pure
      cholesterol and related compounds were approximately 1 ng when a solution of
      cholesterol of 1 microg/mL was spotted onto the surface. Quantitative analysis of
      free cholesterol in serum using reactive DESI was demonstrated using cholesterol
      d7 as internal standard. High throughput analysis of small volumes of serum
      spotted onto a suitable substrate was achieved at an analysis rate of
      approximately 14 s per sample, with a relative standard deviation (RSD) of ca.
      6%. Use of reactive DESI in the imaging mode allowed 2D spatial distributions of
      phospholipids and cholesterol to be recorded simultaneously in rat brain tissues.

PMID- 19746996
TI  - Confocal Raman microscopy investigation of the wetting of reversed-phase liquid
      chromatographic stationary phase particles.
AB  - Wetting phenomena in reversed-phase liquid chromatographic (RPLC) stationary
      phase particles strongly influence the retention of solutes with high water
      content mobile phases. To better understand these phenomena, this work reports
      the spectroscopic observation of the wetting of the interior of individual C(18)
      silica stationary phase particles with acetonitrile-water mobile phase solutions
      by confocal Raman microscopy. It was found that the pores of dry C(18) silica do
      not wet when the concentration of acetonitrile is below 0.12 mol fraction (28% by
      volume). It was also found that there is a wetting hysteresis, where particles
      that had been previously exposed to acetonitrile solutions above the wetting
      transition remain filled with solution even at much lower concentrations of
      acetonitrile in the surrounding solution. Contact angles of acetonitrile-water
      solutions were measured at a planar C(18)-modified silica surface and used to
      predict the capillary wetting of the particles based on the Young-Laplace
      equation. The solution composition at the wetting transition detected by Raman
      microscopy is higher in acetonitrile concentration than predicted by the Young
      Laplace equation, which may be due to the presence of a vapor or air gap at the
      interface between the hydrophobic pores and aqueous solution. Further evidence of
      this behavior is found in water porosimetry results, which show wetting pressures
      approximately 5 times greater than predicted by the Young-Laplace equation and
      are consistent with only 50% of a water interface being in contact with the C(18)
      surface. This fraction increases to 80% at an acetonitrile concentration of 0.12
      mol fraction, leading to spontaneous and irreversible wetting of the hydrophobic
      pores.

PMID- 19746997
TI  - Single-cell pathogen detection with a reverse-phase immunoassay on impedimetric
      transducers.
AB  - The risk of infectious diseases has compelled some industries to establish a zero
      tolerance standard for the presence of microorganisms in a given sample. Here, we
      address this issue with a novel reverse-phase immunoassay on impedimetric
      transducers for the specific detection of extremely low numbers of pathogens
      (less than 10 cells). After simply spotting the sample onto the electrodes,
      physisorbed analytes were targeted with urease-labeled antibodies, and the urease
      on the pathogens hydrolyzed urea to ionic species with a concomitant decrease of
      the resistivity of the solution. By this methodology, the limit of detection
      (LOD) based on the 3sigma criterion was 1 Escherichia coli cell with an assay
      time under 1 h. However, the precise number of cells present in highly diluted
      samples is uncertain, making it difficult to assess the final LOD of the sensor.
      We overcome this problem by using an atomic force microscope to deposit and image
      in situ the exact number cells on the transducer. After performing the
      immunoassay, a single E. coli cell was successfully detected without ambiguity in
      the number of cells even in the presence of a 10(4) excess of a competing
      microorganism, thus demonstrating the outstanding LOD and selectivity of the
      proposed reverse-phase immunoassay.

PMID- 19746998
TI  - Gas phase stabilization of noncovalent protein complexes formed by electrospray
      ionization.
AB  - The use of gas phase additives to stabilize noncovalent protein complexes in
      electrospray ionization mass spectrometry (ES-MS) is demonstrated for two protein
      ligand interactions, an enzyme-small molecule inhibitor complex, and a protein
      disaccharide complex. It is shown that the introduction of gas phase imidazole
      into the ES ion source effectively protects gas phase protein-ligand complexes
      against in-source dissociation. The stabilizing effect of imidazole vapor is
      comparable to that observed upon addition of imidazole to the ES solution. The
      introduction of sulfur hexafluoride, at high partial pressure, into the source
      region also effectively suppresses in-source dissociation of protein complexes.
      It is proposed that evaporative cooling is the primary mechanism responsible for
      the stabilizing effects observed for the gas phase additives.

PMID- 19746999
TI  - Heterometallic aggregates of copper(I) with metalloligand Sn(edt)2 (edt = ethane
      1,2-dithiolate): syntheses and structures of [Sn(edt)2Cl(mu-I)(mu3-I)(CuPPh3)3],
      [Sn(edt)2(mu-Br)2(mu3-Br)2(CuPPh3)4], and [{Sn(edt)2}3(mu-OH)3Cu5(PPh3)8][PF6]2.
AB  - The treatment of a slurry of an equimolar mixture of [Sn(edt)(2)] (edt = ethane
      1,2- dithiolate) and [Et(4)N]Cl.xH(2)O with CuI in the presence of PPh(3) gave a
      tetranuclear compound, [Sn(edt)(2)Cl(mu-I)(mu(3)-I)(CuPPh(3))(3)] (1), which
      consists of a rectangular-pyramidal [Sn(edt)(2)Cl](-) moiety ligated by three
      [Cu(PPh(3))](+) fragments via the sulfur atoms of the edt(2-) ligands. The
      treatment of a slurry of [Sn(edt)(2)] and excess [Et(4)N]Br with
      [Cu(MeCN)(4)][PF(6)] in the presence of PPh(3) afforded a pentanuclear compound,
      [Sn(edt)(2)(mu-Br)(2)(mu(3)-Br)(2)(CuPPh(3))(4)] (2), which comprises two
      [(CuPPh(3))(2)(mu-Br)](+) fragments symmetrically ligating an octahedral trans
      [Sn(edt)(2)Br(2)](2-) moiety via the sulfur and bromide atoms. Reaction of
      [Sn(edt)(2)] with [Cu(MeCN)(4)][PF(6)] and PPh(3) in a mixed MeCN/CH(2)Cl(2)
      solution yielded a novel octanuclear compound, [{Sn(edt)(2)}(3)(mu
      OH)(3)Cu(5)(PPh(3))(8)][PF(6)](2) (3), which may be described as a triangular
      [{Sn(edt)(2)}(3)(mu-OH)(3)](3-) core chelated by three [Cu(PPh(3))(2)](+) species
      and capped by two [Cu(PPh(3))](+) species. The luminescent properties of
      compounds 1, 2, and 3 were investigated in a CH(2)Cl(2) solution at room
      temperature. Upon excitation at lambda > 360 nm, these compounds are luminescent
      in CH(2)Cl(2) solution with emissions having maxima at 422, 515, and 494 nm,
      respectively.

PMID- 19747000
TI  - Complex formation and molecular structure of neptunyl(VI) and -(V) acetates.
AB  - Stability and coordination of neptunyl(VI) and -(V) acetate complexes in aqueous
      solution were studied by using UV-vis-near-IR (NIR) and X-ray absorption fine
      structure (XAFS) spectroscopy. In the neptunyl(VI) acetate system, the formation
      of Np(VI)O(2)(AcO)(+), Np(VI)O(2)(AcO)(2)(aq), and Np(VI)O(2)(AcO)(3)(-) was
      detected. Both spectroscopic methods provided similar stability constants: log
      K(1) = 2.98 +/- 0.01, log beta(2) = 4.60 +/- 0.01, and log beta(3) = 6.34 +/-
      0.01 from UV-vis-NIR and log K(1) = 2.87 +/- 0.03, log beta(2) = 4.20 +/- 0.06,
      and log beta(3) = 6.00 +/- 0.01 from XAFS at I = 0.30 M (H,NH(4))ClO(4). Extended
      XAFS (EXAFS)-derived structural data for Np(VI)O(2)(2+)(aq), Np(VI)O(2)(AcO)(+),
      and Np(VI)O(2)(AcO)(3)(-) were consistent with their stoichiometry, showing a
      bidentate coordination of acetate (Np-O(ax) = 1.76-1.77 A; Np-O(eq) = 2.43-2.47
      A; Np-C(c) = 2.87 A; Np-C(t) = 4.38 A). Similar to Np(VI), Np(V) forms also three
      different complexes with acetate. The stability constants of Np(V)O(2)(AcO)(aq),
      Np(V)O(2)(AcO)(2)(-), and Np(V)O(2)(AcO)(3)(2-) were determined by UV-vis-NIR
      titration to log K(1) = 1.93 +/- 0.01, log beta(2) = 3.11 +/- 0.01, and log
      beta(3) = 3.56 +/- 0.01 at I = 0.30 M (H,NH(4))ClO(4). The present result is
      corroborated by the structural information from EXAFS (Np-O(ax) = 1.83-1.85 A; Np
      O(eq) = 2.51 A; Np-C(c) = 2.90-2.93 A) and by the electrochemical behavior of the
      Np(V/VI) redox couple in the presence of AcOH as a function of the pH.

PMID- 19747001
TI  - Mononuclear and polynuclear copper(II) complexes derived from
      pyridylalkylaminomethylphenol polypodal ligands.
AB  - Four mononuclear complexes [Cu(HL(1))Cl]PF(6).CH(3)OH (1),
      [Cu(HSL(1))Cl]PF(6).0.75H(2)O (2), [Cu(HL(2))Cl]PF(6).CH (3)OH (3),
      [Cu(HSL(2))Cl]PF(6).1.5CH(3)OH (4), and two polynuclear complexes [Cu
      (2)(SL(2))(2)](PF(6))(2).2CH(3)OH (5) and {Cu[Cu(SL(2))(Cl)](2)}(PF(6))(2) (6)
      (HL(1): 2-[(bis(2-pyridylmethyl)-amino)methyl]-4-methylphenol; HSL(1): 2-[(bis(2
      pyridylmethyl)amino) methyl]-4-methyl-6-(methyl-thio)phenol; HL(2): 2-[(2
      pyridylmethyl)(2'-pyridylethyl)-aminomethyl)]-4-methylphenol; HSL(2): 2-[(2
      pyridylmethyl)(2'-pyridylethyl)amino-methyl]-4-methyl-6-(methylthio)phenol were
      obtained and characterized. The crystal structures of the mononuclear complexes 1
      4 show the copper centers in a square-base pyramidal environment with the
      phenolic oxygen coordinated at the axial position. Dinuclear complex 5 has two
      copper centers with different geometry and bridged by phenoxo oxygens; one of the
      copper atoms is square pyramidal while the other can be described with a highly
      distorted octahedral geometry with a long Cu-S distance (2.867 A). Density
      functional theory calculations were used to obtain the reported structure of 6,
      since single crystals suitable for X-ray diffraction were not isolated. Magnetic
      studies done for 5 and 6 show an antiferromagnetic behavior for 5 (J = -134 cm(
      1)) and a ferromagnetic behavior for 6 (J = +11.9 cm(-1)). Redox potentials for
      the mononuclear complexes were measured by cyclic voltammetry; the values show
      the effect of the chelating ring size (-213 mV and -142 mV for Cu-HL(1) and Cu
      HL(2), respectively) and the presence of the thiomethyl substituent (-213 mV and 
      184 mV for Cu-HL(1) and Cu-HSL(1), respectively).

PMID- 19747002
TI  - Alkali-metal-mediated manganation(II) of naphthalenes: constructing metalla
      anthracene and metalla-phenanthrene structures.
AB  - Alkali-metal-mediated manganation (AMMMn) reactions of the synergic base sodium
      monoalkyl-bisamidomanganate [(tmeda)Na(tmp)(CH(2)SiMe(3))Mn(tmp)] (1) with
      naphthalene, 1-methoxynaphthalene, or 2-methoxynaphthalene are reported. These
      novel direct manganation [Mn(II)] reactions produced the crystalline ortho
      manganated naphthyl products [(tmeda)Na(tmp)(2-C(10)H(7))Mn(tmp)] (3),
      [(tmeda)Na(tmp){2-(1-MeOC(10)H(6))}Mn(CH(2)SiMe(3))] (4), and [(tmeda)Na(tmp){3
      (2-MeOC(10)H(6))}Mn(tmp)] (5) in reasonable to good isolated yields of 88, 65,
      and 85%, respectively. All three new complexes have been crystallographically
      characterized, showing discrete molecular structures with trigonal planar Mn
      centers forming sigma bonds to the deprotonated C atoms of the naphthyl ligands,
      whereas Na interacts with the aromatic pi system in 3 or with the MeO substituent
      in 4 and 5. These latter interactions lead to interesting 5,6,7,8
      tetrahydrophenanthrene-like and 1,2,3,4-tetrahydroanthracene-like metallacyclic
      motifs in 4 and 5, respectively. The sensitivity of these AMMMn reactions to
      impurities has been illustrated in the serendipitous preparation of the
      benzenediide complex [(tmeda)(2)Na(2)(tmp)(2)(1,4-C(6)H(4))Mn(2)(tmp)(2)] (6)
      from one attempted repeat synthesis of 5. An "open inverse crown" arrangement
      with a 1,4-dimanganated benzene molecule is revealed in the crystal structure of
      6.

PMID- 19747003
TI  - Anopheles gambiae alkaline phosphatase is a functional receptor of Bacillus
      thuringiensis jegathesan Cry11Ba toxin.
AB  - Alkaline phosphatases (ALPs, EC 3.1.3.1) isolated from lepidopteran and dipteran
      species are identified as receptors for Cry1Ac and Cry11Aa toxins, respectively
      [Jurat-Fuentes, J. L., and Adang, M. J. (2004) Eur. J. Biochem. 7, 3127-3135;
      Fernandez, L. E., et al. (2006) Biochem. J. 396, 77-84]. In our study, an
      alkaline phosphatase cDNA (AgALP1) was cloned from the midgut of Anopheles
      gambiae larvae. The encoded 63 kDa protein has a predicted
      glycosylphosphatidylinositol (GPI) anchor omega-site ((526)Asp), an N
      glycosylation site ((239)Asn-Leu-Thr), and an O-glycosylation site ((312)Ser).
      AgALP1(t) was expressed in Escherichia coli and used to prepare antiserum and to
      analyze the interaction of AgALP with mosquitocidal Cry11Ba toxin. Anti-AgALP
      serum localized AgALP to the apical brush border in the anterior and posterior
      midgut of larvae and detected a 65 kDa species on a blot of brush border membrane
      vesicles (BBMVs) protein prepared from larvae. ALP activity was released from
      larval BBMVs prepared by phosphatidylinositol-specific phospholipase C (PIPLC)
      treatment, and after separation by two-dimensional gel electrophoresis and
      blotting, a chain of doublet spots at 65 kDa was detected by anti-AgALP. A subset
      of these doublet spots bound Cry11Ba on a reprobed blot. Heterologously expressed
      AgALP1(t) bound [(125)I]Cry11Ba on dot blots and reduced the level of binding of
      [(125)I]Cry11Ba to brush border membrane vesicles by 41%, a percentage comparable
      to that of unlabeled Cry11Ba and aminopeptidase AgAPN2(t1) peptide. AgALP1(t)
      binds Cry11Ba toxin with a high affinity (23.9 nM) and shares a binding site on
      Cry11Ba with AgAPN2(t1). In bioassays against An. gambiae larvae, the presence of
      AgALP1(t) reduced larval mortality from 78 to 8%. We conclude that AgALP1 is a
      binding protein and a functional receptor for Cry11Ba toxin.

PMID- 19747004
TI  - N-terminal acetylation of the neuronal protein SNAP-25 is revealed by the SMI81
      monoclonal antibody.
AB  - The monoclonal antibody SMI81 binds SNAP-25, a major player in neurotransmitter
      release, with high affinity and has previously been used to follow changes in the
      levels of this protein in neuropsychiatric disorders. We report here that the
      SMI81 epitope is present at the extreme N-terminus of SNAP-25 and, unusually,
      cannot be recognized when present as an internal sequence. Although it is known
      that SNAP-25 can be palmitoylated and phosphorylated in brain, we now reveal the
      existence of a third modification, acetylation of the N-terminus. This
      acetylation event greatly increases the efficiency of SMI81 antibody binding. We
      show that this highly specific antibody can be used for studying brain function
      in many vertebrate organisms.

PMID- 19747005
TI  - Mechanisms of interactions of the nucleotide cofactor with the RepA protein of
      plasmid RSF1010. Binding dynamics studied using the fluorescence stopped-flow
      method.
AB  - The dynamics of the nucleotide binding to a single, noninteracting nucleotide
      binding site of the hexameric helicase RepA protein of plasmid RSF1010 has been
      examined, using the fluorescence stopped-flow method. The experiments have been
      performed with fluorescent analogues of ATP and ADP, TNP-ATP and TNP-ADP,
      respectively. In the presence of Mg(2+), the association of the cofactors
      proceeds as a sequential three-step process [Formula: see text] The sequential
      nature of the mechanism indicates the lack of significant conformational
      equilibria of the helicase prior to nucleotide binding. The major conformational
      change of the RepA helicase-nucleotide complex occurs in the formation of (H
      N)(2), which is characterized by a very high value of the partial equilibrium
      constant and large positive changes in the apparent enthalpy and entropy. Strong
      stabilizing interactions between subunits of the RepA hexamer contribute to the
      observed dynamics and energetics of the internal transitions of the formed
      complexes. Magnesium cations mediate the efficient and fast conformational
      transitions of the protein, in a manner independent of the structure of the
      cofactor phosphate group. The ssDNA bound to the enzyme preferentially selects a
      single intermediate of the RepA-ATP analogue complex, (H-N)(2), while the DNA has
      no effect on the intermediates of the RepA-ADP complex. Allosteric interactions
      between the nucleotide- and DNA-binding site are established in the initial
      stages of formation of the complex. Moreover, in the presence of the single
      stranded DNA, all the transitions in the nucleotide binding to the helicase
      become sensitive to the structure of the phosphate group of the cofactor.

PMID- 19747006
TI  - Multidrug-resistant Gram-negative infections: what are the treatment options?
AB  - The emergence of multidrug-resistant (MDR) Gram-negative bacilli creates a
      challenge in the treatment of nosocomial infections. While the pharmaceutical
      pipeline is waning, two revived old antibacterials (colistin and fosfomycin), a
      newer one (tigecycline) and an 'improved' member of an existing class (doripenem)
      are the only therapeutic options left. The class of polymyxins, known since 1947
      and represented mostly by polymyxin B and polymyxin E (colistin), has recently
      gained a principal role in the treatment of the most problematic MDR Gram
      negative pathogens (such as Pseudomonas aeruginosa, Acinetobacter baumannii,
      Klebsiella pneumoniae and Stenotrophomonas maltophilia). Future prospective
      studies are needed to answer important clinical questions, such as the possible
      benefit of combination with other antimicrobials versus monotherapy, the efficacy
      of colistin in neutropenic hosts and the role of inhaled colistin. As new
      pharmacokinetic data emerge, clarification of the pharmacokinetic/pharmacodynamic
      (PK/PD) profile of colistin as well as appropriate dosing seems urgent, while
      development of resistance must be carefully monitored. Fosfomycin tromethamine, a
      synthetic salt of fosfomycin discovered in 1969, has regained attention because
      of its in vitro activity against extended-spectrum beta-lactamase (ESBL)
      producing Enterobacteriaceae and MDR P. aeruginosa. Although in use for decades
      in oral and parenteral formulations for a variety of infections without
      significant toxicity, its clinical utility in MDR infections remains to be
      explored in future studies. Tigecycline, the first representative of the new
      class of glycylcyclines, holds promise in infections from MDR K. pneumoniae (K.
      pneumoniae carbapenemase [KPC]- and ESBL-producing strains) and
      Enterobacteriaceae with various mechanisms of resistance. The in vitro activity
      of tigecycline against A. baumannii makes it a tempting option, as it is
      currently the most active compound against MDR strains along with colistin.
      However, the usual minimum inhibitory concentration values of this pathogen are
      approximately 2 mg/L and compromise clinical outcomes based on PK/PD issues. Its
      advantageous penetration into various tissues is useful in infections of the skin
      and soft tissues as well as intra-abdominal infections (official indications),
      whereas low serum concentrations compromise its use in bloodstream infections.
      Therefore, prospective studies with dose escalation are urgently needed, as well
      as clarification of its role in nosocomial pneumonia, after poor results in the
      study of ventilator-associated pneumonia. Finally, doripenem, the recently
      licensed member of the carbapenems (without significant spectrum alterations from
      the ascendant members) seems to possess a lower potential for resistance
      selection and a more favourable pharmacokinetic profile when given as an extended
      infusion. The latter strategy could prove helpful in overcoming low level
      resistance of A. baumannii and P. aeruginosa strains.

PMID- 19747007
TI  - Emerging treatments in cystic fibrosis.
AB  - There are a number of potential drugs for the treatment of cystic fibrosis (CF)
      currently undergoing clinical studies. A number of antibacterials formulated for
      delivery by inhalation are at various stages of study; these include dry-powder
      inhaler versions of colistin, tobramycin and ciprofloxacin, and formulations of
      azteonam, amikacin, levofloxacin, ciprofloxacin and fosfomycin/tobramycin for
      nebulization. Clinical trials of anti-inflammatory agents, including glutathione,
      phosphodiesterase-5 inhibitors such as sildenafil, oral acetylcysteine,
      simvastatin, methotrexate, docosahexaenoic acid, hydroxychloroquine, pioglitazone
      and alpha1-antitrypsin, are ongoing. Ion channel modulating agents, such as
      lancovutide (Moli1901, duramycin) and denufosol, which activate alternate (non-CF
      transmembrane regulator [CFTR]) chloride channels, and GS 9411, a sodium channel
      antagonist, are now at the stages of clinical study and if successful, will offer
      a new category of therapeutic agent for the treatment of CF. Correction of the
      underlying gene effect, either by agents that help to correct the dysfunctional
      CFTR, such as ataluren, VX-770 and VX-809, or by gene transfer (gene therapy), is
      a particularly exciting prospect as a new therapy for CF and clinical studies are
      ongoing. This article reviews the exciting potential drug treatments for CF
      currently being evaluated in clinical studies, and also highlights some of the
      challenges faced by research and clinical teams in assessing the efficacy of
      potential new therapies for CF.

PMID- 19747008
TI  - Histone deacetylase inhibitors: current status and overview of recent clinical
      trials.
AB  - Histone deacetylase (HDAC) inhibitors are a new group of anticancer agents that
      have a potential role in the regulation of gene expression, induction of cell
      death, apoptosis and cell cycle arrest of cancer cells by altering the
      acetylation status of chromatin and other non-histone proteins. In clinical
      trials, HDAC inhibitors have demonstrated promising antitumour activity as
      monotherapy in cutaneous T-cell lymphoma and other haematological malignancies.
      In solid tumours, several HDAC inhibitors have been shown to be efficacious as
      single agents; however, results of most clinical trials were in favour of using
      HDAC inhibitors either prior to the initiation of chemotherapy or in combination
      with other treatments. Currently, the molecular basis of response to HDAC
      inhibitors in patients is not fully understood. In this review, we summarize the
      current status of HDAC inhibitors, as single agents or in combination with other
      agents in different phases of clinical trials. In most of the clinical trials,
      HDAC inhibitors were tolerable and exerted biological or antitumor activity. HDAC
      inhibitors have been studied in phase I, II and III clinical trials with variable
      efficacy. The combination of HDAC inhibitors with other anticancer agents
      including epigenetic or chemotherapeutic agents demonstrated favourable clinical
      outcome.

PMID- 19747009
TI  - Refractory gastro-oesophageal reflux disease: diagnosis and management.
AB  - Refractory gastro-oesophageal reflux disease (GORD) is described when reflux
      symptoms have not responded to 4-8 weeks of proton pump inhibitor therapy and
      occurs in a heterogeneous mixture of patients. The causes of refractory GORD
      include inadequate acid suppression, non-acid gastro-oesophageal reflux, and non
      reflux causes of GORD symptoms including achalasia, gastroparesis and functional
      heartburn. Upper gastrointestinal tract endoscopy should initially be performed
      to identify the presence of oesophagitis, and exclude other diagnoses including
      eosinophilic oesophagitis and peptic ulcer disease. Patients with refractory
      symptoms but with a normal upper endoscopy are more difficult to diagnose and may
      require ambulatory pH monitoring, impedance testing, oesophageal motility tests
      and gastric emptying scans. The primary goal of treatment is symptom reduction
      and eventual elimination, which can be achieved with proper identification of the
      underlying cause of the symptoms.

PMID- 19747010
TI  - Optimizing the use of thrombolytics in ST-segment elevation myocardial
      infarction.
AB  - The advent of thrombolytic therapy was a major advance in the treatment of ST
      segment elevation myocardial infarction (STEMI). The administration of
      fibrinolytic reperfusion therapy can reduce mortality rates by as much as 30%,
      with the greatest benefit observed if therapy is administered soon after symptom
      onset. Outcomes with thrombolytic therapy are improved if there is adjunctive
      treatment with aspirin, clopidogrel and an anti-thrombin agent. Although there is
      evidence that primary percutaneous coronary intervention (PCI) is the most
      effective reperfusion strategy, the majority of hospitals still do not have PCI
      capabilities and, thus, thrombolytic therapy remains a cornerstone of treatment
      for STEMI. Trials of thrombolytic therapy have demonstrated that initial patency
      rates can approach 85%, but there is still a need for improvement of non-invasive
      markers that predict failure or re-occlusion of the infarct-related artery.
      Because of the overwhelming data demonstrating the importance of rapid
      reperfusion, current studies are examining the role of earlier treatment of
      patients with STEMI via pre-hospital administration and/or coordinated systems
      for rapid diagnosis, transfer and delivery of definitive care. Facilitated PCI, a
      strategy of thrombolytic therapy followed by immediate PCI, has not been shown to
      be beneficial and current studies are examining the optimal timing of coronary
      angiography after thrombolytic therapy.

PMID- 19747011
TI  - Degarelix.
AB  - Degarelix is a gonadotropin-releasing hormone (GnRH) receptor antagonist that, in
      common with GnRH receptor agonists (e.g. leuprolide, goserelin and triptorelin),
      is indicated for use as an androgen-deprivation therapy in patients with advanced
      prostate cancer. In 1-year, randomized, open-label, phase II or III trials in
      patients with all stages of prostate cancer, subcutaneous degarelix was
      associated with rapid, profound and sustained suppression of serum testosterone
      and prostate-specific antigen (PSA), without evidence of testosterone surges or
      microsurges. In the phase III trial, degarelix (240 mg initially followed by 80
      mg every 28 days) was considered to be effective and noninferior to intramuscular
      leuprolide (7.5 mg every 28 days) with regard to inducing and maintaining
      suppression of serum testosterone to castrate levels (i.e. <or=0.5 ng/mL).
      Degarelix induced testosterone suppression more rapidly than leuprolide. Median
      serum testosterone levels of <or=0.5 ng/mL were achieved by day 3 in degarelix
      recipients, but not until day 28 in leuprolide recipients. PSA suppression was
      also more rapid with degarelix than with leuprolide, with significant between
      group differences in serum PSA levels favouring degarelix at 14 and 28 days.
      Degarelix treatment for 1 year was generally well tolerated; the adverse events
      reported were mostly related to subcutaneous drug administration (i.e. injection
      site reactions) and hormonal androgen deprivation (e.g. hot flushes).

PMID- 19747012
TI  - Prothrombin complex concentrate (Beriplex P/N).
AB  - Beriplex P/N, a prothrombin complex concentrate derived from pooled human plasma,
      contains the vitamin K-dependent coagulation factors II, VII, IX and X, and the
      vitamin K-dependent coagulation inhibition proteins C and S. Intravenous Beriplex
      P/N provided rapid and sustained normalization of elevated international
      normalized ratios and controlled bleeding in adult patients participating in
      several prospective, noncomparative clinical studies (n = 8-43), with these data
      supported by clinical experience during its use over more than a decade. Based on
      extensive clinical experience, Beriplex P/N is also effective in the treatment of
      congenital deficiency of any of the vitamin K-dependent coagulation factors when
      purified specific coagulation factor products are not available. Over a decade of
      clinical experience and more limited data from clinical studies have shown that
      intravenous infusions of Beriplex P/N were generally well tolerated in adult
      patients with acquired or congenital deficiencies of the vitamin K-dependent
      coagulation factors. To date, there have been no proven cases of viral
      transmission reported in any published studies.

PMID- 19747013
TI  - Liraglutide: a review of its use in type 2 diabetes mellitus.
AB  - Liraglutide (Victoza) is an acylated analogue of glucagon-like peptide-1 (GLP-1)
      indicated for the treatment of type 2 diabetes mellitus. In phase III studies,
      once-daily subcutaneous liraglutide improved glycaemic control compared with
      placebo or active comparator in adult patients with type 2 diabetes, both as
      monotherapy and in combination with one or two oral antidiabetic drugs such as
      metformin, sulfonylureas or thiazolidinediones. Liraglutide provided
      significantly better glycaemic control than rosiglitazone or insulin glargine in
      combination trials. At appropriate dosages, liraglutide was noninferior to
      glimepiride with respect to glycaemic control in a combination trial, but
      provided significantly better control than glimepiride or glibenclamide in
      monotherapy trials. Liraglutide improved pancreatic beta-cell function, generally
      led to weight loss, and was associated with a low risk of hypoglycaemia.
      Liraglutide was generally well tolerated, with the most common adverse events
      being gastrointestinal events, such as nausea, which decreased over time. Thus,
      liraglutide is an effective treatment option for use in patients with type 2
      diabetes mellitus.

PMID- 19747014
TI  - Bosentan: a review of its use in the management of digital ulcers associated with
      systemic sclerosis.
AB  - Bosentan (Tracleer) is an orally administered dual endothelin-1 (ET-1) receptor
      antagonist approved in the EU for reducing the number of new digital ulcers in
      patients with systemic sclerosis and ongoing digital ulcer disease. Oral bosentan
      therapy was beneficial and generally well tolerated in patients with digital
      ulcers associated with systemic sclerosis. In well designed, placebo-controlled
      trials, bosentan treatment significantly reduced the number of new ulcers, but
      had no effect on ulcer healing, in patients with digital ulcers. Adverse events
      associated with bosentan were consistent with those seen during treatment for
      other indications, with major concerns being the potential for teratogenicity and
      hepatotoxicity, for which regular liver function monitoring is recommended.
      Overall, considering the large unmet need for therapeutic options in patients
      with digital ulcers, bosentan extends the treatment options available to patients
      with systemic sclerosis-associated digital ulcers.

PMID- 19747015
TI  - Redescription of Gyropus parvus (Ewing, 1924) (Insecta: Phthiraptera: Amblycera:
      Gyropidae) from tucos-tucos (Rodentia: Ctenomyidae: Ctenomys ) in Patagonia,
      Argentina.
AB  - A detailed redescription of Gyropus parvus (Insecta: Phthiraptera: Amblycera:
      Gyropidae) is given based on specimens collected from the type host, Ctenomys
      colburni Allen 1903 , and the type locality, Estancia Huanuluan, Provincia de Rio
      Negro, Argentina. We expand and provide new chaetotaxy. New scanning electron
      microscopy images showing microstructural details of adults and eggs of G. parvus
      obtained from topotype specimens are included. Sexual dimorphism was mainly shown
      by differences in body size and abdominal chaetotaxy, with females being 17.5%
      larger than males and with more setae in each cluster. Significant differences
      between males and females were also observed in sternal plate measurements.
      Features described here show homogeneity within type host population. This
      information contributes to our knowledge of intra- and inter-specific variability
      for parasite populations. Our investigation constitutes the first collection of
      G. parvus from the type host and locality since it was described.

PMID- 19747016
TI  - A new species of Pseudodelphis (Dracunculoidea: Guyanemidae) in the intertidal
      fish Scartichthys viridis (Blenniidae) from central Chile.
AB  - A new species of nematode, Pseudodelphis chilensis n. sp., is described. This
      parasite was found in muscles of the pectoral fins of a blenniid fish,
      Scartichthys viridis , from central Chile. The new species differs from the other
      2 described (P. oligocotti Adamson and Roth, 1990 and P. limnicola Brugni and
      Viozzi, 2006) for its longer glandular esophagus and a small caecum at the
      beginning of the glandular esophagus; both characteristics are in males and
      females. In addition, the male of P. chilensis n. sp. does not have an adanal
      caudal papillae, and it has longer spicules than the other 2 species. This is the
      first Pseudodelphis species described for Chile and the second for South America.

PMID- 19747017
TI  - Plasmodium berghei ookinetes glide and release Pbs25 and circumsporozoite
      thrombospondin-related protein on solid surface substrata.
AB  - Plasmodium spp. development within mosquito vectors includes invasive ookinete
      and sporozoites stages, which display gliding movements during invasion of the
      midgut and salivary glands, respectively. Sporozoite gliding has been well
      documented, and several proteins released during sporozoite's locomotion have
      been described. However, proteins on the ookinete gliding trails are poorly
      described. In the present study, we documented that 2 proteins, Pbs25 and
      circumsporozoite thrombospondin-related protein (CTRP), are released during
      Plasmodium berghei ookinete gliding on a solid surface substrate.

PMID- 19747018
TI  - Anisakid larvae in Atlantic salmon (Salmo salar L.) grilse and post-smolts:
      molecular identification and histopathology.
AB  - The molecular identification and histopathology are described for the parasitic
      larvae of a nematode species present in the abdominal cavity of Atlantic salmon (
      Salmo salar ) grilse caught in fish traps on their natal river in the west of
      Ireland and post-smolts collected during experimental trawls on the continental
      shelf edge of the northeast Atlantic Ocean. Larvae in the adult and juvenile
      salmon were identified as Anisakis simplex sensu stricto by PCR amplification and
      RFLP and sequencing of the ITS gene and PCR amplification and sequencing of the
      cox2 gene. Parasitic nematode larvae in the grilse were either encapsulated in
      the abdominal mesentery associated with the pyloric ceca or on the serosal
      surface of the liver and in the vent region. In some fish, larvae were found in
      the parenchyma of the liver and muscularis circularis of the intestine. In
      general, the larvae induced a limited cellular response apart from the occurrence
      of focal melanin macrophage aggregates and individual eosinophilic granular cells
      in the connective tissue capsule. Melanin macrophage aggregates were also present
      among the hepatocytes adjacent to encapsulated larvae in the liver. The reaction
      to the parasites was more severe in the wall of the intestine. Encapsulated
      nematode larvae caused displacement, vacuolation, and necrosis of the circular
      muscle fibers. The stratum compactum was also disrupted with focal areas of
      degeneration. Overall, the intestinal wall had a hypercellular appearance with
      extensive cellular infiltration comprising eosinophilic granular cells,
      macrophages, lymphocytes, and fibrocytes. The post-smolts were caught in May
      during the early oceanic phase of their life cycle. In these fish, A. simplex
      sensu stricto larvae were found lying free on the serosal surface of the
      intestine and liver without any apparent histologic changes. This is the earliest
      in the marine migration of Atlantic salmon that A. simplex sensu stricto
      infection has been recorded.

PMID- 19747019
TI  - Identification of differentially expressed genes in early stages of Eimeria
      tenella by suppression subtractive hybridization and cDNA microarray.
AB  - Avian coccidiosis, a major parasitic disease of poultry, is caused by Eimeria
      spp. infection. It inflicts severe economic losses on the poultry industry
      worldwide. To further understand the molecular basis of sporulation and invasion
      of Eimeria spp., suppression subtractive hybridization and microarray approaches
      were combined to identify novel and important genes involved in the development
      and invasion of the early stages of Eimeria tenella . Three subtractive cDNA
      libraries were constructed for 3 stages of E. tenella including unsporulated
      oocysts, sporulated oocysts, and sporozoites. A subset of clones was selected
      from the 3 subtractive libraries to construct cDNA microarrays. Microarray
      analysis was used to assay expression changes of these clones. A total of 657
      valid expressed sequence tags (ESTs) was obtained, including 119 unique
      sequences, 31 from sporulated oocysts and 88 from sporozoites. Homology searches
      of the public sequence databases showed that, among the 119 ESTs, 32 genes
      encoded proteins homologous with previously reported proteins including microneme
      proteins and surface antigen proteins of E. tenella , small heat shock proteins,
      rhoptry proteins of Toxoplasma gondii , and calcium-dependent protein kinase of
      Plasmodium spp. Thus, the remaining 87 ESTs have not previously been reported.
      Further characterization of these differentially expressed genes will be useful
      in understanding those responsible for sporulation, invasion, growth, and
      development of E. tenella .

PMID- 19747020
TI  - Designing programs for populations with chronic care needs: a blanket or a quilt?

PMID- 19747021
TI  - Effect of a managed care disease management program on diabetes care.
AB  - OBJECTIVE: To determine if processes and outcomes of diabetes care improved
      between 2000 and 2006 in a managed care health plan with a comprehensive diabetes
      disease management program. STUDY DESIGN: Cross-sectional. METHODS: A total of
      1650 randomly selected members with diabetes mellitus completed surveys in 2000,
      and 1256 randomly selected members with diabetes completed surveys in 2006.
      Survey and medical record data were analyzed using multivariable regression and
      predictive probabilities adjusted for age, education, and comorbidities. RESULTS:
      In 2006, patients were more likely to have proteinuria assessed (85% vs 74% in
      2000), foot examinations performed (90% vs 86%), glycosylated hemoglobin levels
      measured (94% vs 87%), lipids measured (81% vs 70%), aspirin use recommended (67%
      vs 56%), and influenza immunizations administered (70% vs 63%). Glycosylated
      hemoglobin levels decreased by 0.60% (P <.001), systolic blood pressures by 3 mm
      Hg (P = .002), and low-density lipoprotein cholesterol levels by 18 mg/dL (P
      <.001). Those who were continuously enrolled in the health plan were
      significantly more likely to report having had dilated retinal examinations (P =
      .003), aspirin use recommendations (P = .049), influenza immunizations (P =
      .004), and lower low-density lipoprotein cholesterol levels (by 6 mg/dL, P =
      .003). CONCLUSIONS: Implementation of a disease management program was associated
      with substantial improvements in processes and outcomes of diabetes care over 6
      years. Although secular trend likely contributed somewhat, improvement in other
      measures was significantly associated with duration of enrollment in the health
      plan, making secular trend an unlikely explanation for all of our findings.

PMID- 19747022
TI  - Prior authorization to improve testing of glycosylated hemoglobin in a managed
      care setting.
AB  - OBJECTIVE: To ascertain whether revocation of a prior authorization (PA)
      requirement by the Leumit Health Fund of Israel resulted in inferior rates of
      glycosylated hemoglobin (A1C) testing among new users of expensive diabetes
      medications. STUDY DESIGN: Electronic patient record (EPR) database study.
      METHODS: Data on new users of the target drugs and on A1C testing in these
      patients were extracted from EPR databases for the 6-month period after the
      revocation. The proportion (95% confidence interval [CI]) of patients who
      obtained at least 1 A1C test during the 4 months before initiation of treatment
      was calculated. The data were stratified by month to detect possible trends in
      rates of testing during the period after the policy change. RESULTS: After the PA
      requirement was rescinded, A1C testing among incident users of the target drugs
      dropped from 100% during the PA period to rates ranging from 85.6% (95% CI, 79.7%
      91.5%) to 94.4% (95% CI, 90.8%-97.9%). Statistically significant variance in
      monthly rates of testing was not observed. CONCLUSIONS: Prior authorization has
      been successfully implemented in the managed care setting studied to obtain 100%
      performance of a laboratory test necessary to monitor drug therapy outcomes in
      patients with diabetes mellitus. When PA is implemented as a quality assurance
      strategy, its revocation should be accompanied by continuing education efforts
      designed to maintain optimal adherence to recommendations for appropriate care.

PMID- 19747023
TI  - Diabetes care quality: insurance, health plan, and physician group contributions.
AB  - OBJECTIVE: To study the relative contributions of insurance product (commercial,
      Medicaid, Medicare), health plan, and physician group to quality of diabetes
      care. STUDY DESIGN: Cross-sectional observational study using data reported by
      Minnesota Community Measurement (MNCM) on care provided in 2005. METHODS:
      Individual performance rates for glycosylated hemoglobin (A1C) level <7%,
      lowdensity lipoprotein cholesterol (LDL-C) level <100 mg/dL, blood pressure
      <30/80 mm Hg, documented tobacco-free status, and aspirin use, as well as an all
      or-none composite measure (Optimal Diabetes Care), were obtained from MNCM for 57
      physician groups. Results included 7169 patients connected with 1 of 8 health
      plans and 1 of 3 types of insurance product. RESULTS: All factors studied had a
      relationship to quality results. Of the factors, insurance product has the
      strongest relationship to A1C, LDL-C, and Optimal Diabetes Care. Health plan had
      the strongest relationship to tobacco-free status and daily aspirin, and
      physician group had the strongest relationship to blood pressure control.
      Physician group results varied more than those for health plan or insurance
      product on most measures. CONCLUSIONS: All factors studied contribute to diabetes
      quality results. Reporting both physician group performance and health plan
      performance may offer a greater opportunity to improve care than reporting only
      health plan or only physician group results.

PMID- 19747024
TI  - Type 2 diabetes mellitus in China: a preventable economic burden.
AB  - OBJECTIVES: To estimate the direct and indirect costs of type 2 diabetes mellitus
      (T2DM) in China in 2007 and project these costs for the year 2030, and to examine
      and compare the benefits of selected interventions. STUDY DESIGN: Annual direct
      costs of medical and nonmedical care and indirect costs of income losses were
      estimated through case calculation of data from a cross-sectional survey carried
      out in 4 major Chinese cities from March 2007 to September 2007. METHODS: The
      subjects were consecutively recruited T2DM outpatients and inpatients from 20
      secondary and tertiary hospitals using selection probability proportional to size
      sampling. We combined the existing data from cost-effectiveness studies into the
      case estimation to examine the benefits of the observed regime of interventions
      for preventing and treating diabetes. RESULTS: Annual direct medical and direct
      nonmedical costs per case averaged 1320.90 USD and 180.80 USD, respectively. The
      mean annual indirect costs of T2DM and its complications were estimated to be
      206.10 USD. Based on case numbers in 2007 and projected case numbers in 2030, the
      direct medical costs of T2DM and its complications were estimated to be 26.0
      billion USD in 2007 and were projected to be 47.2 billion USD in 2030.
      CONCLUSIONS: The results indicated that T2DM consumes a large portion of
      healthcare expenditures and will continue to place a heavy burden on health
      budgets in the future. Preventive intervention, screening, and treatment
      strategies may effectively decrease the incidence and complications of diabetes
      and therefore save costs.

PMID- 19747025
TI  - Cost-effectiveness of Roux-en-Y gastric bypass in type 2 diabetes patients.
AB  - OBJECTIVE: To assess the cost-effectiveness of Roux-en-Y gastric bypass for
      treating type 2 diabetes mellitus (T2DM) in the United States compared with
      standard medical management, using clinical data from a prospective observational
      study conducted at an academic medical center. STUDY DESIGN: Our study used a
      predictive health economic model (the CORE Diabetes Model) to project the long
      term costs and clinical effectiveness of Roux-en-Y gastric bypass as a treatment
      for T2DM using the prospective observational study as the basis for our clinical
      effectiveness assumptions. METHODS: The CORE Diabetes Model used Monte Carlo
      simulation with tracker variables to estimate the lifetime costs and clinical
      outcomes of Roux-en-Y gastric bypass compared with standard medical management of
      obese T2DM patients. Sensitivity analyses were performed on key clinical
      assumptions, discount rates, and shorter time horizons. RESULTS: The base-case
      scenario yielded an incremental cost-effectiveness ratio (ICER) of $21,973 per
      quality-adjusted life-year (QALY) gained. In sensitivity analyses, shortening the
      time horizon to 5 and 10 years and excluding the negative impact of increased
      body mass index on the patient's quality of life had the greatest adverse impact
      on the ICERs (ie, higher cost per QALY). CONCLUSIONS: Under base-case
      assumptions, Roux-en-Y gastric bypass is cost-effective in the treatment of T2DM
      in the United States with an ICER below $50,000 per QALY gained. Sensitivity
      analyses indicated that bariatric surgery is not cost-effective over shorter time
      horizons, or if the negative quality-of-life impact of increased body mass index
      is ignored.

PMID- 19747026
TI  - Suboptimal identification of obesity by family physicians.
AB  - OBJECTIVES: To examine how family physicians identify and document obesity. STUDY
      DESIGN: Prospective cross-sectional study of 289 patients in 7 family practice
      clinics of Clalit Health Services in Israel. METHODS: Two hundred eighty-nine
      patients from 7 family practice clinics had their body mass index (BMI
      [calculated as weight in kilograms divided by height in meters squared])
      determined by the study staff and subsequently compared with the data retrieved
      from the family practices' database regarding physicians' BMI documentation and
      obesity diagnosis. Demographic variables, comorbidities, and medication use were
      also extracted. Multivariate odds ratios (ORs) and 95% confidence intervals (CIs)
      were obtained to determine the predictors of BMI documentation. RESULTS: Seventy
      eight of 289 patients (27.0%) were obese (BMI, > or =30.0), and 126 (43.6%) were
      overweight (BMI range, 25.0 to < or =29.9). Body mass index was documented in 39
      of 78 obese patients (50.0%) and in 49 of 126 overweight patients (38.9%) (P
      <.001). Diagnosis of obesity was recorded in 19 of 78 obese patients (24.4%).
      Older patients (OR, 2.77; 95% CI, 1.39-5.49) and obese patients (OR, 2.04; 95%
      CI, 1.04-3.99) were more likely to have their weight and height measured and BMI
      calculated by their physician. Patients with comorbid conditions such as diabetes
      mellitus (OR, 4.35; 95% CI, 2.20-8.62) and hypertension (OR, 3.20; 95% CI, 1.71
      5.99) and patients taking chronic medications (OR, 3.44; 95% CI, 1.20-9.83) were
      also more likely to have their BMI documented. CONCLUSIONS: Family physicians
      failed to identify most obese and overweight patients, as seen by lack of BMI
      documentation and concordant diagnoses in the medical problem list. Determination
      of BMI by physicians in family practice is of utmost importance, and its
      incorporation into medical care should be optimized.

PMID- 19747027
TI  - Patient adherence: a blind spot in cost-effectiveness analyses?
AB  - BACKGROUND: Despite evidence that medication adherence can influence cost
      effectiveness analysis (CEA) results, the extent to which published CEAs include
      adherence has not been fully characterized. OBJECTIVES: To characterize inclusion
      of patient adherence in CEAs of self-administered medications and to examine
      whether industry sponsorship affects adherence inclusion, because adherence
      exclusion might overstate the interventions' cost-effectiveness. STUDY DESIGN:
      Systematic review of the English-language medical literature published between
      1998 and 2003 identified 177 original CEAs of self-administered medications.
      METHODS: Two trained readers independently abstracted data. Adherence inclusion
      was estimated overall and by study characteristics. Predictors of inclusion were
      assessed with chi2 tests and logistic regression. RESULTS: Among 177 CEAs, 30.5%
      explicitly modeled adherence; of these, only half modeled adherence in both base
      case and sensitivity analyses. Only 21% of studies performed sensitivity analysis
      on adherence; fewer than half of these provided sufficient information to
      determine the impact on results. Of the remaining 20 studies, 9 were sensitive to
      adherence. Adherence inclusion varied across clinical areas (P = .022). Only 30%
      of chronic anticoagulation studies, 52% of cardiovascular risk reduction studies,
      38% of neuropsychiatric studies, and 32% of HIV antiretroviral studies considered
      suboptimal adherence. Among 128 CEAs that disclosed study sponsorship, adherence
      was included in 25.4% of industry-sponsored and 35.1% of non-industrysponsored
      studies (P = .17). CONCLUSIONS: Few CEAs modeled suboptimal medication adherence.
      As CEAs are meant to model "real world" costs and effects of interventions,
      investigators would do well to explicitly consider medication adherence in the
      future.

PMID- 19747028
TI  - Toyota production system quality improvement initiative improves perioperative
      antibiotic therapy.
AB  - OBJECTIVE: To assess the role of a Toyota production system (TPS) quality
      improvement (QI) intervention on appropriateness of perioperative antibiotic
      therapy and in length of hospital stay (LOS) among surgical patients. STUDY
      DESIGN: Pre-post quasi-experimental study using local and national retrospective
      cohorts. METHODS: We used TPS methods to implement a multifaceted intervention to
      reduce nosocomial methicillin-resistant Staphylococcus aureus infections on a
      Veterans Affairs surgical unit, which led to a QI intervention targeting
      appropriate perioperative antibiotic prophylaxis. Appropriate perioperative
      antibiotic therapy was defined as selection of the recommended antibiotic agents
      for a duration not exceeding 24 hours from the time of the operation. The local
      computerized medical record system was used to identify patients undergoing the
      25 most common surgical procedures and to examine changes in appropriate
      antibiotic therapy and LOS over time. RESULTS: Overall, 2550 surgical admissions
      were identified from the local computerized medical records. The proportion of
      surgical admissions receiving appropriate perioperative antibiotics was
      significantly higher (P <.01) in 2004 after initiation of the TPS intervention
      (44.0%) compared with the previous 4 years (range, 23.4%-29.8%) primarily because
      of improvements in compliance with antibiotic therapy duration rather than
      appropriate antibiotic selection. There was no statistically significant decrease
      in LOS over time. CONCLUSION: The use of TPS methods resulted in a QI
      intervention that was associated with an increase in appropriate perioperative
      antibiotic therapy among surgical patients, without affecting LOS.

PMID- 19747029
TI  - Medicare Part D: selected issues for plan sponsors, pharmacists, and
      beneficiaries in 2009.
AB  - BACKGROUND: The Medicare Drug Benefit was designed to provide coverage for
      outpatient prescriptions to Medicare beneficiaries. Since its inception in
      January 2006, there have been numerous refinements; however, the overall purpose
      and structure of the benefit remain the same. OBJECTIVES: To (1) review changes
      to the benefit for 2009 and (2) describe the Part D provisions of the Medicare
      Improvements for Patients and Providers Act of 2008. METHODS: We reviewed policy
      statements and other communications from the Centers for Medicare & Medicaid
      Services released between January 1, 2008, and September 30, 2008, and the
      Medicare Improvements for Patients and Providers Act of 2008. RESULTS: Changes to
      Part D in 2009 include availability of Part D data, changes in the coverage
      amounts in the standard drug benefit, outreach to vulnerable populations, the
      United States Pharmacopeia 3-year cycle, revisions to the best-available-evidence
      policy, new standards for e-prescribing, and new guidance for medication therapy
      management programs. CONCLUSIONS: Various refinements and clarifications to the
      benefit have been made to date; however, opportunities for improvement remain.
      The availability of Part D data will allow researchers to determine the impact of
      drugs on overall health outcomes and costs for Medicare beneficiaries.

PMID- 19747030
TI  - Are there unintended consequences of step-therapy programs?

PMID- 19747031
TI  - Percutaneous lithotripsy in Valdivia-Galdakao decubitus position: our experience.
AB  - Percutaneous nephrolithotripsy (PNL) is actually the first therapeutic option to
      resolve complex renal stones. Our department initiated its experience in 1985 and
      treated the first 585 patients in ventral decubitus, as the original technique
      was described. Then, in 1998, the dorsal decubitus was adopted (Valdivia Uria),
      in which 695 patients were treated. Since 2006 the Valdivia Galdakao variant has
      been used. The Valdivia Galdakao position is an intermediate dorsal decubitus
      with extension of its homolateral lower limb and flexion of the contralateral. It
      is a practical way to place the patient for percutaneous renal surgery, avoiding
      hyperextensions and hyperflexions that can result in articular damage. It
      preserves cardiovascular and ventilatory dynamics and allows a better access to
      the respiratory tract. In this position, the bowel slips away from the puncture
      area lowering the risk of its damage. A single lumbar and genital sterile
      surgical field is created allowing antegrade and retrograde simultaneous
      endoscopic and even laparoscopic access, increasing efficiency and safety of the
      minimal invasive procedures. Between April 2006 and March 2008, 175 PNLs were
      performed in our department with the patient in Valdivia Galdakao position. The
      aim of this article is to describe our experience in this decubitus confirming
      that the Valdivia Galdakao is a safe, practical and versatile position that
      should be considered as first choice when a percutaneous renal surgery is
      indicated.

PMID- 19747032
TI  - Chinese minimally invasive percutaneous nephrolithotomy: the Guangzhou
      experience.
AB  - BACKGROUND AND PURPOSE: Percutaneous nephrolithotomy (PCNL) using a small tract
      is controversial, and its indication is considered limited. In our center,
      however, we have performed Chinese minimally invasive PCNL regularly for managing
      upper-tract calculi. We report our experience. PATIENTS AND METHODS: Our
      technique is not just about using smaller instruments and tracts. Our overall
      approach is different from the standard PCNL. We preferred a middle caliceal
      puncture via the 11th rib space and also relied mainly on a strong irrigant
      current for stone fragment removal. We reviewed and analyzed the prospectively
      collected database on patients who underwent minimally invasive (MPCNL) from 2001
      to 2005. RESULTS: A total of 4760 MPCNL procedures were performed in 3610
      kidneys. There were 1240 staghorn stones and 85 ureteral stones. There were 14
      transplanted kidneys and 27 cases of horseshoe kidneys. The average operative
      time was 78 minutes. The stone-free rate at postoperative day 2 was 89%. The
      major complication rate was 0.86%. CONCLUSION: Our experience with the Chinese
      MPCNL shows that it is safe and effective for managing all kinds of upper-tract
      calculi.

PMID- 19747033
TI  - Modified device-free HAL: an innovative cost-reductive approach.
AB  - Hand-assisted laparoscopy (HAL) has been in vogue since 1994. The major
      advantages are tactile sensation, quicker dissection, and easy removal of
      specimen. These advantages could not be availed in developing countries due to
      the cost of the available HAL devices. This has initiated the use of HAL without
      devices in our unit. Instead of a device, a double glove with a sponge between
      the inner and outer glove at the wrist acted as an obturating cuff. A muscle
      splitting incision in the iliac fossa helped in minimizing the air leak. In this
      article, we report our experience in nephrectomy and nephroureterectomy.

PMID- 19747034
TI  - Single-incision transumbilical laparoscopic sleeve gastrectomy.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy has been gaining popularity due to
      its simplicity and outstanding results. This procedure is no exception to
      attempts aimed at minimizing abdominal port access. In this article, the senior
      author (AAS) presents his technique for an entirely transumbilical single
      incision approach where no extraumbilical incisions are necessary. MATERIALS AND
      METHODS: Seven patients underwent laparoscopic sleeve gastrectomies using this
      single-incision, totally transumbilical technique. The same surgeon (AAS)
      performed all surgical interventions. The same perioperative protocol and
      operative techniques were implemented for all the patients. RESULTS: A total of 7
      single-incision transumbilical laparoscopic sleeve gastrectomies were
      successfully performed using this technique. Two patients required lysis of
      adhesions, and 1 patient underwent an umbilical hernia repair during the
      procedure. Mean operating time was 143 minutes. One of the patients required the
      insertion of an additional trocar. There were no mortalities or postoperative
      complications noted during the mean follow-up period of 1.5 months. CONCLUSIONS:
      Single-incision laparoscopic sleeve gastrectomy performed entirely through the
      umbilicus is safe, technically feasible, and reproducible.

PMID- 19747035
TI  - Effects of laser photobiomodulation on cutaneous wounds treated with mitomycin C:
      a histomorphometric and histological study in a rodent model.
AB  - AIM: The aim of the present study was to assess histologically the effect of
      Laser Photobiomodulation (LPBM) on skin wounds treated with Mitomycin C (MMC).
      BACKGROUND DATA: Wound healing occurs because of a competitive mechanism between
      the synthesis and lyses of collagen. Therefore, any factor that increases the
      lyses or reduces the synthesis of collagen may result in changes in the healing
      process. MMC is an antineoplastic drug that inhibits fibroblast proliferation,
      collagen synthesis, and neoangiogenesis. LPBM has been shown to stimulate wound
      healing, increasing the production of collagen, fibroblastic proliferation, and
      angiogenesis. MATERIALS AND METHODS: Forty-eight Wistar rats were randomly
      distributed into 4 main groups (n = 12): G1--control (G1a--7 d and G1b--14 d); G2
      -MMC (G2a--7 d and G2b--14 d); G3--MMC + lambda660 nm laser (G3a--7 d and G3b--14
      d); and G4--MMC + lambda790 nm laser (G4a--7 d and G4b--14 d). Under general
      anesthesia, one excisional wound was created on the dorsum of each animal. Two ml
      of MMC solution was applied to the wound 4 h after surgery for 5 min. LPBM was
      performed on groups G3 (lambda690 nm; 20 J/cm(2); 30 mW; Phi = 2 mm) and G4
      (lambda790 nm; 20 J/cm(2); 40 mW; Phi = 2 mm), starting immediately after the
      application of the MMC and repeated every other day during the experimental
      period. Laser light was applied transcutaneously at 4 equidistant points on the
      wound margin (4 x 5 J/cm(2), 20 J/cm(2)/session). The specimens were routinely
      cut and processed to wax. The slides were stained with HE and Sirius red.
      Computerized hystomorphometry was performed. RESULTS: LPBM resulted in reduced
      inflammation and an increase in both fibroblast proliferation and collagen
      deposition. CONCLUSION: The use of LPBM improves wound healing in subjects
      treated with MMC.

PMID- 19747036
TI  - Screening for constipation in palliative care patients.
AB  - INTRODUCTION: The objective of this study was to establish screening criteria for
      constipation in palliative care and, subsequently, to determine data for
      diagnostic suspicion of constipation in a palliative care population. Also we
      investigate the incidence of fecal impaction in the same sample of palliative
      care patients. MATERIALS AND METHODS: A descriptive, multicenter cross-sectional
      study was done. All patients in active care by a group of hospital and home
      palliative care teams were studied. A questionnaire on signs (frequency and
      consistency of stools) and symptoms (pain, discomfort, or a sensation of
      incomplete evacuation when having a bowel movement) of constipation in last
      weeks, and a verbal numerical scale (VNS) (0-10) on discomfort or difficulty with
      constipation was completed by the patients. The patients were asked about
      impaction in the last 3 months. RESULTS: One hundred twenty patients from 21
      palliative care teams were included; the majority of patients received opiates
      (66%) and also laxatives (60%). Bowel movement rate less than three stools per
      week was found in 13% of patients, stools harder than normal were experienced in
      24% patients, and 33% exhibited pain, discomfort, or sensation of incomplete
      evacuation. Of the patients studied 13% had some signs of habitual constipation
      but they did not complain of symptoms, others (17%) had some discomfort in spite
      of not having signs of constipation. As screening criteria for constipation in
      palliative care we elected to include indistinct presence of constipation
      symptoms or constipation signs in recent weeks. A diagnosis of suspicion of
      constipation was established in almost 1 of 2 patients (48%) of our palliative
      care population. VNS with cutoff point of 3 or more of 10, showed a sensitivity
      of 0.70 and a specificity of 0.74 and positive predictive value (PPV) of 73%
      positive and negative predictive value (NPV) of 70%. In addition to these
      findings a considerable number of our palliative care patients (20%) reported
      episodes of fecal impaction in the last 3 months. CONCLUSION: The screening for
      constipation in palliative care should be performed exploring subjective symptoms
      and other objective signs. A diagnosis of suspected constipation was found in
      almost half of the palliative care patients studied. A VNS of constipation did
      not produce good predictive values for the detection of constipation in our
      sample.

PMID- 19747037
TI  - Hurdles and sorting by inversions: combinatorial, statistical, and experimental
      results.
AB  - As data about genomic architecture accumulates, genomic rearrangements have
      attracted increasing attention. One of the main rearrangement mechanisms,
      inversions (also called reversals), was characterized by Hannenhalli and Pevzner
      and this characterization in turn extended by various authors. The
      characterization relies on the concepts of breakpoints, cycles, and obstructions
      colorfully named hurdles and fortresses. In this paper, we study the probability
      of generating a hurdle in the process of sorting a permutation if one does not
      take special precautions to avoid them (as in a randomized algorithm, for
      instance). To do this we revisit and extend the work of Caprara and of Bergeron
      by providing simple and exact characterizations of the probability of
      encountering a hurdle in a random permutation. Using similar methods we provide
      the first asymptotically tight analysis of the probability that a fortress exists
      in a random permutation. Finally, we study other aspects of hurdles, both
      analytically and through experiments: when are they created in a sequence of
      sorting inversions, how much later are they detected, and how much work may need
      to be undone to return to a sorting sequence.

PMID- 19747038
TI  - A fast and exact algorithm for the median of three problem: a graph decomposition
      approach.
AB  - Abstract In a previous article, we have shown that adequate subgraphs can be used
      to decompose multiple breakpoint graphs, achieving a dramatic speedup in solving
      the median problem. In this article, focusing on the median of three problem, we
      prove more important properties about adequate subgraphs with rank 3 and discuss
      the algorithms inventorying simple adequate subgraphs. After finding simple
      adequate subgraphs of small sizes, we incorporate them into ASMedian, an
      algorithm to solve the median of three problem. Results on simulated data show
      dramatic speedup so that many instances can be solved very quickly, even ones
      containing hundreds or thousands of genes.

PMID- 19747039
TI  - Reduced high-density lipoprotein 2b in non-obese type 2 diabetic patients
      analysed by a microfluidic chip method in a case-control study.
AB  - BACKGROUND: Alterations in high-density lipoprotein (HDL) subfractions,
      especially in the HDL2b subfraction, have been reported in type 2 diabetes
      mellitus (T2DM). However, new methods for convenient and reliable quantitation of
      HDL2b are yet to be developed. METHODS: Thirty-eight patients with T2DM were
      enrolled and age-, sex- and body mass index (BMI)-matched controls were selected
      from the same population. A microfluidic chip method was employed to analyse
      serum HDL subfractions. RESULTS: The microfluidic chip method revealed a
      significant reduction in HDL2b and its ratio to total HDL in T2DM patients. There
      was a reverse correlation for total HDL and HDL2b, and its ratio with
      triglycerides, homeostasis model assessment-insulin sensitivity index (HOMA-IS)
      and insulin resistance index (HOMA-IR). CONCLUSIONS: We have shown a reduction of
      HDL2b and its ratio to total HDL by a novel chip method in T2DM patients. The
      significant correlation between HDL2b and HOMA-IS and HOMA-IR may have further
      predictive value in clinical utility.

PMID- 19747040
TI  - Management of hemorrhagic complications associated with percutaneous
      nephrolithotomy.
AB  - Urologists have witnessed replacement of complex open surgical procedures with
      minimally invasive therapies over the past quarter century. Nothing personifies
      this more than an anatrophic nephrolithotomy in the management of kidney stones.
      The Boyce procedure, once the gold standard for staghorn calculi, is rarely
      performed. Percutaneous nephrolithotomy (PCNL) has become the gold standard
      procedure for large renal stones and staghorns. This article will review the
      hemorrhagic complications that are associated with PCNL and the necessary
      therapeutic interventions.

PMID- 19747041
TI  - Diagnosis and management of postpercutaneous nephrolithotomy residual stone
      fragments.
AB  - Residual stone fragments can occur in up to 8% of patients who are treated with
      percutaneous nephrolithotomy (PCNL). When left untreated, approximately half of
      these patients will experience a stone-related event, for which more than half
      will need a secondary surgical intervention. Predictors of adverse events are a
      residual fragment larger than 2 mm that is located in the pelvis or ureter.
      Preventive measures for the creation of residual fragments include a carefully
      selected access giving exposure to the bulk of the stone, the creation of
      multiple tracts, the use of single pulse pneumatic lithotripsy, the prevention of
      stone migration with ureteral balloons or stone cones, and careful flushing of
      the stones from the collecting system. Plain radiography of the kidneys, ureters,
      and bladder, linear tomography, and ultrasonography have all been used to judge
      the result of PCNL and to detect the presence of residual fragments. Thin-slice,
      unenhanced helical CT, however, is more sensitive and should be performed at 1
      month after surgery. While medical therapy and shockwave lithotripsy possess a
      minor role, second-look flexible nephroscopy and/or flexible ureterorenoscopy
      seem to be the treatments of choice for residual stone fragments after PCNL.

PMID- 19747042
TI  - Implication of 5-aminolevulinic acid fluorescence of the ventricular wall for
      postoperative communicating hydrocephalus associated with cerebrospinal fluid
      dissemination in patients with glioblastoma multiforme: a report of 7 cases.
AB  - OBJECT: Fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA) has been
      broadly recognized as a beneficial tool for the resection of glioblastoma
      multiforme (GBM). Fluorescence in the ventricular walls, which were apparently
      free of macroscopic tumor or MR imaging enhancement indicative of CSF
      dissemination, was detected during surgery for GBM. To evaluate the clinical
      significance of the 5-ALA fluorescence, the authors resected ventricle wall
      tissue together with the adjacent tumors for pathological examination and then
      followed up the clinical courses of the patients. METHODS: Seven consecutive GBMs
      located near the lateral ventricle were surgically treated using a fluorescence
      guided technique with 5-ALA at the authors' hospital since acquiring
      instrumentation for the detection of 5-ALA fluorescence in 2007. All of the
      procedures were performed using a ventricular entry, and 5-ALA fluorescence of
      the ventricular wall was detected despite the absence of macroscopic tumor
      invasion of the wall. RESULTS: A pathological examination of the resected
      ventricular wall tissues revealed tumor cells in 6 of the 7 cases and disruption
      of the ependymal cell layer in all 7 cases. Delayed communicating hydrocephalus
      followed surgery in all 7 patients, and ventricular wall enhancements on MR
      imaging were demonstrated after hydrocephalus in 2 of the patients. CONCLUSIONS:
      Data in this study suggest that 5-ALA fluorescence of the ventricular wall may be
      predictive of postoperative hydrocephalus associated with CSF dissemination even
      in cases without evidence of CSF dissemination on MR imaging studies before
      surgery. The authors also speculate that postoperative radiotherapy covering the
      whole ventricular system may be a better therapeutic option for these patients.

PMID- 19747043
TI  - A comprehensive analysis of hearing preservation after radiosurgery for
      vestibular schwannoma.
AB  - OBJECT: Gamma Knife surgery (GKS) has evolved into a practical alternative to
      open microsurgical resection in the treatment of patients with vestibular
      schwannoma (VS). Hearing preservation rates in GKS series suggest very favorable
      outcomes without the possible acute morbidity associated with open microsurgery.
      To mitigate institutional and practitioner bias, the authors performed an
      analytical review of the published literature on the GKS treatment of vestibular
      schwannoma patients. Their aim was to objectively characterize the prognostic
      factors that contribute to hearing preservation after GKS, as well as
      methodically summarize the reported literature describing hearing preservation
      after GKS for VS. METHODS: A comprehensive search of the English-language
      literature revealed a total of 254 published studies reporting assessable and
      quantifiable outcome data obtained in patients who underwent radiosurgery for
      VSs. Inclusion criteria for articles were 4-fold: 1) hearing preservation rates
      reported specifically for VS; 2) hearing status reported using the American
      Association of Otolaryngology-Head and Neck Surgery (AAO-HNS) or Gardner
      Robertson classification; 3) documentation of initial tumor size; and 4) GKS was
      the only radiosurgical modality in the treatment. In the analysis only patients
      with AAO-HNS Class A or B or Gardner-Robertson Grade I or II status at the last
      follow-up visit were defined as having preserved hearing. Hearing preservation
      and outcome data were then aggregated and analyzed based on the radiation dose,
      tumor volume, and patient age. RESULTS: The 45 articles that met the authors'
      inclusion criteria represented 4234 patients in whom an overall hearing
      preservation rate was 51%, irrespective of radiation dose, patient age, or tumor
      volume. Practitioners who delivered an average < or = 13-Gy dose of radiation
      reported a higher hearing preservation rate (60.5% at < or = 13 Gy vs 50.4% at >
      13 Gy; p = 0.0005). Patients with smaller tumors (average tumor volume < or = 1.5
      cm(3)) had a hearing preservation rate (62%) comparable with patients harboring
      larger tumors (61%) (p = 0.8968). Age was not a significant prognostic factor for
      hearing preservation rates as in older patients there was a trend toward improved
      hearing preservation rates (56% at < 65 years vs 71% at > or = 65 years of age; p
      < 0.1134). The average overall follow-up in the studies reviewed was 44.4 +/- 32
      months (median 35 months). CONCLUSIONS: These data provide a methodical overview
      of the literature regarding hearing preservation with GKS for VS and a less
      biased assessment of outcomes than single-institution studies. This objective
      analysis provides insight into advising patients of hearing preservation rates
      for GKS treatment of VSs that have been reported, as aggregated in the published
      literature. Analysis of the data suggests that an overall hearing preservation
      rate of approximately 51% can be expected approaching 3-4 years after
      radiosurgical treatment, and the analysis reveals that patients treated with < or
      = 13 Gy were more likely to have preserved hearing than patients receiving larger
      doses of radiation. Furthermore, larger tumors and older patients do not appear
      to be at any increased risk for hearing loss after GKS for VS than younger
      patients or patients with smaller tumors.

PMID- 19747044
TI  - True posterior communicating artery aneurysms: are they more prone to rupture? A
      biomorphometric analysis.
AB  - OBJECT: Posterior communicating artery (PCoA) aneurysms can occur at the junction
      with the internal carotid artery, posterior cerebral artery (PCA), or the
      proximal PCoA itself. Hemodynamic stressors contribute to aneurysm formation and
      may be associated with parent vessel size and aneurysm location. This study
      evaluates the correlation of various biomorphometric characteristics in 2 of the
      aforementioned types of PCoA aneurysms. METHODS: Patients with PCoA aneurysms
      were analyzed using CT angiography. Source images and reconstructions were used
      to determine which aneurysms originated purely from the PCoA and those that
      originated from the internal carotid artery/PCoA junction. Morphometric analysis
      was performed on the aneurysm, the precommunicating segment of the PCA (P(1)),
      the ambient segment of the PCA (P(2)), and both PCoA arteries and were correlated
      to clinical presentation. Parametric and nonparametric analyses were performed to
      test for significance. RESULTS: A total of 77 PCoA aneurysms were analyzed, and
      10 were found to be true PCoA aneurysms (13.0%). The ipsilateral PCoA/P(1) ratio
      (1.77 +/- 0.44 vs 0.82 +/- 0.46, p = 0.0001) and ipsilateral P(2)/P(1) ratio
      (1.73 +/- 0.40 vs 1.22 +/- 0.41, p = 0.0003) were significantly larger in true
      PCoA aneurysms. Interestingly, aneurysm size was statistically larger in the
      junctional aneurysms (0.14 +/- 0.1 vs 0.072 +/- 0.04 cm(3), p = 0.03). The
      prevalence of ruptured aneurysms was similar in both groups (approximately 80%, p
      value not significant). CONCLUSIONS: These data suggest that true PCoA aneurysms
      have a larger PCoA relative to the ipsilateral P(1) segment. To the authors'
      knowledge, this represents the first such biomorphometric comparison of these
      different types of PCoA aneurysms. Although statistically smaller in size, true
      PCoA aneurysms also have a similar prevalence of presenting as a ruptured
      aneurysm, suggesting that they might be more prone to rupture than a junctional
      aneurysms of similar size. Further analysis will be required to determine the
      biophysical factors affecting rupture rates.

PMID- 19747045
TI  - Raymond M. P. Donaghy: a pioneer in microneurosurgery.
AB  - Raymond M. P. Donaghy was one of the true pioneers of modern neurosurgery. His
      restless dedication, innovation, and desire to humbly disseminate his knowledge
      facilitated the advancement of the field of microneurosurgery. Many of his
      trainees--most notably M. Gazi Yasargil--continued to advance the field,
      developing innovative microsurgical instruments and techniques. The history of
      microneurosurgery is incomplete without a glimpse at the life of this remarkable
      man.

PMID- 19747046
TI  - Intraaneurysmal balloon assistance for navigation across a wide-necked aneurysm.
AB  - Endovascular obliteration of wide-necked aneurysms may be precluded by the
      inability to navigate across the aneurysm neck. The authors present a technique
      in which a Hyperform balloon is inflated within the aneurysm and used as a
      contact surface to "bounce" the remodeling balloon across the aneurysm neck. They
      have successfully used this technique in 3 patients to efficiently overcome
      vessel tortuosity, aneurysmal dead space, and balloon prolapse, allowing for
      obliteration of large, wide-necked aneurysms.

PMID- 19747047
TI  - The apolipoprotein E epsilon4 allele and outcome in severe traumatic brain injury
      treated by an intracranial pressure-targeted therapy.
AB  - OBJECT: In this paper, the authors' goal was to study the influence of the
      apolipoprotein E epsilon4 allele on the clinical outcome in patients treated for
      severe traumatic brain injury (TBI) with an intracranial pressure (ICP)-targeted
      therapy based on the Lund concept. METHODS: The authors conducted a prospective
      double-blinded randomized trial in which they examined patients with severe TBI.
      Inclusion criteria consisted of a Glasgow Coma Scale (GCS) score < or = 8 at the
      time of intubation and sedation, patient age between 15 and 70 years, an initial
      cerebral perfusion pressure > 10 mm Hg, and arrival to the hospital < 24 hours
      after trauma. Blood samples for the analysis of apolipoprotein E allele types
      were collected. Independent staff members evaluated outcomes by obtaining Glasgow
      Outcome Scale (GOS) scores at 3, 12, and 24 months. RESULTS: The occurrence of
      the epsilon4 allele was analyzed in 46 patients (mean age 35 +/- 2.2 years with a
      median GCS score of 6 [range 3-8]). The epsilon4 allele was present in 39.1% of
      the patients. The ICP, cerebral perfusion pressure, and injury severity score
      were not statistically significantly different between the groups. The median GOS
      score at 3 months was 3.5, and at 12 and 24 months was 4 (range 1-5). Except for
      the GOS score at 3 months, which was dichotomized as favorable (GOS Score 4 or 5)
      and unfavorable (GOS Scores 1-3), no statistically significant differences in
      outcome, irrespective of GOS dichotomization used, were found between the
      patients with the epsilon4 allele and those without. The presence of the epsilon4
      allele did not predict for clinical outcome, but GCS and ICP did. CONCLUSIONS:
      The presence of epsilon4 is not associated with long-term clinical outcome in
      patients with severe TBI treated with an ICP targeted therapy, based on the Lund
      concept.

PMID- 19747048
TI  - Biopsy versus resection in the management of malignant gliomas: a systematic
      review and meta-analysis.
AB  - OBJECT: The aim of this study was to answer the question whether quality of life
      and progression-free and overall survival are increased in adults with
      supratentorial malignant glioma who are treated with cytoreductive resection as
      compared with those who only undergo biopsy. METHODS: A literature search of the
      electronic databases MEDLINE, EMBASE, and CENTRAL was performed to identify
      relevant studies published before May 2008. Hand-searching of reference lists of
      the identified studies and relevant review articles was also performed. A study
      was considered eligible, regardless of study design (prospective or
      retrospective), if: 1) quality of life and/or progression-free and/or overall
      survival was compared among adult patients undergoing biopsy or resection, and 2)
      patient age and Karnofsky Performance Scale scores were not significantly
      different among the 2 groups compared. RESULTS: One randomized controlled trial
      and 4 retrospective studies (involving a total of 1111 patients) were found
      eligible for this systematic review. A meta-analysis of the eligible studies
      demonstrated a significant increase in overall survival in the patients treated
      with resection instead of biopsy (hazard ratio 0.61, 95% CI 0.52-0.71, p <
      0.0001, fixed-effect model). Although statistical pooling was not feasible, the
      available data suggest that quality of life was increased in patients treated
      with resection rather than biopsy, while there did not seem to be any significant
      difference in progression-free survival between the 2 groups. CONCLUSIONS: Based
      on the best available evidence, it appears that cytoreductive resection in adults
      with supratentorial malignant glioma is associated with improved overall survival
      as compared with biopsy. However, well-designed prospective studies are needed
      for more solid conclusions to be drawn.

PMID- 19747049
TI  - Trigeminal neuralgia.

PMID- 19747050
TI  - Computed tomography angiography, perfusion computed tomography, and a drug
      eluting stent for the treatment of in-stent restenosis of the middle cerebral
      artery.
AB  - The authors report a case of in-stent restenosis (ISR) of the middle cerebral
      artery (MCA) following bare-metal stent (BMS) deployment and subsequent treatment
      using a drug-eluting stent (DES). This 65-year-old woman presented with frequent
      transient ischemic attacks. Initial studies revealed occlusion of the left
      internal carotid artery and severe stenosis of the right MCA with decreased
      cerebral perfusion in the bilateral MCA territories. Stent-assisted angioplasty
      of the right MCA was performed using a BMS, and satisfactory results were
      obtained with no complications. Six months after the procedure the patient
      presented with recurrent symptoms, and workups revealed ISR with decreased
      cerebral perfusion. A DES was successfully placed without complications. Follow
      up studies at 3 and 8 months after retreatment showed sustained luminal integrity
      and cerebral perfusion. A combination of CT angiography and perfusion CT
      exhibited the anatomical results and hemodynamic status of the stenotic lesion,
      and these findings coincided with the patient's clinical symptoms and the results
      of conventional cerebral angiography. In-stent restenosis of the MCA after
      placement of a BMS can be treated using a DES. A combination of CT angiography
      and perfusion CT can be an alternative to conventional angiography. Low-profile
      devices with an amelioration of trackability are essential for the further
      incorporation of the DES into the field of endovascular neurosurgery. More
      clinical experiences and long-term follow-ups are mandatory to evaluate the
      safety, efficacy, and durability of the DES.

PMID- 19747051
TI  - Toward understanding recurrent meningioma: the potential role of lysosomal
      cysteine proteases and their inhibitors.
AB  - OBJECT: The first aim of this study was to diagnose more aggressive and
      potentially recurrent meningiomas using an in vitro embryonic chick heart
      invasiveness assay in which lysosomal enzyme cathepsin B was used as the
      invasiveness marker. The second aim was to confirm if cathepsin B and/or
      cathepsin L and their endogenous inhibitors were also prognostic parameters in
      the clinical study of 119 patients with meningioma. METHODS: Primary meningioma
      cultured spheroids were "confronted" with embryonic chick heart spheroids in
      vitro, and cathepsin B was used as molecular marker to immunolabel the invasive
      tumor cells. In vitro invasion assays of the malignant meningioma cells were used
      to assess the invasive potential related to the cysteine cathepsins. As to the
      second aim, the possible association of cathepsin B along with selected molecular
      markers, cathepsin L, and endogenous cysteine protease inhibitors (stefins A and
      B and cystatin C) with meningioma malignancy was determined using enzyme-linked
      immunosorbent assays in tumor homogenates. Univariate and multivariate analyses
      were used to compare these parameters with established biological markers of
      meningioma recurrence in 119 patients with meningiomas. RESULTS: The more
      invasive tumors, which characteristically overgrew the normal tissue, were
      identified even within a group of histologically benign meningiomas. More
      intensive staining of cathepsin B in these tumors was not only found at the tumor
      front, but also in the invading pseudopodia of a single migrating tumor cells.
      Matrigel invasion of malignant meningioma cells was significantly altered by
      modulating cathepsin B activity and by stefin B silencing. In the clinical
      samples of meningioma, the levels of cathepsins B and L, stefin B, and cystatin C
      were highest in the tumors of higher histological grades, whereas stefin A and
      progesterone receptor were the only markers that were significantly increased and
      decreased, respectively, in WHO Grade III lesions. With respect to the prognosis
      of relapse, cathepsin L (p = 0.035), stefin B (p = 0.007), cystatin C (p =
      0.008), and progesterone receptor (p = 0.049) levels were significant, whereas
      cathepsin B was not a prognosticator. As expected, WHO grade, age, and Simpson
      grade (complete tumor resection) were prognostic, with Simpson grade only
      relevant in the short term (up to 90 months) but not in longer-term follow-up. Of
      note, the impact of all these parameters was lost in multivariate analysis, due
      to overwhelming prognostic impact of stefin B (p = 0.039). CONCLUSIONS: The data
      indicate that the cysteine cathepsins and their inhibitors are involved in a
      process related to early meningioma recurrence, regardless of their histological
      classification. Of note, the known tumor invasiveness marker cathepsin B,
      measured in whole-tumor homogenates, was not prognostic, in contrast to its
      endogenous inhibitor stefin B, which was highly significant and the only
      independent prognostic factor to predict meningioma relapse in multivariate
      analysis and reported herein for the first time. Stefin B inhibition of local
      invasion was confirmed by in vitro invasion assay, although its other functions
      cannot be excluded.

PMID- 19747052
TI  - Comparison of diffusion tensor imaging tractography of language tracts and
      intraoperative subcortical stimulations.
AB  - OBJECT: Diffusion tensor (DT) imaging tractography is increasingly used to map
      fiber tracts in patients with surgical brain lesions to reduce the risk of
      postoperative functional deficit. There are few validation studies of DT imaging
      tractography in these patients. The aim of this study was to compare DT imaging
      tractography of language fiber tracts by using intraoperative subcortical
      electrical stimulations. METHODS: The authors included 10 patients with low-grade
      gliomas or dysplasia located in language areas. The MR imaging examination
      included 3D T1-weighted images for anatomical coregistration, FLAIR, and DT
      images. Diffusion tensors and fiber tracts were calculated using in-house
      software. Four tracts were reconstructed in each patient including the arcuate
      fasciculus, the inferior occipitofrontal fasciculus, and 2 premotor fasciculi
      (the subcallosal medialis fiber tract and cortical fibers originating from the
      medial and lateral premotor areas). The authors compared fiber tracts
      reconstructed using DT imaging with those evidenced using intraoperative
      subcortical language mapping. RESULTS: Seventeen (81%) of 21 positive
      stimulations were concordant with DT imaging fiber bundles (located within 6 mm
      of a fiber tract). Four positive stimulations were not located in the vicinity of
      a DT imaging fiber tract. Stimulations of the arcuate fasciculus mostly induced
      articulatory and phonemic/syntactic disorders and less frequently semantic
      paraphasias. Stimulations of the inferior occipitofrontal fasciculus induced
      semantic paraphasias. Stimulations of the premotor-related fasciculi induced
      dysarthria and articulatory planning deficit. CONCLUSIONS: There was a good
      correspondence between positive stimulation sites and fiber tracts, suggesting
      that DT imaging fiber tracking is a reliable technique but not yet optimal to map
      language tracts in patients with brain lesions. Negative tractography does not
      rule out the persistence of a fiber tract, especially when invaded by the tumor.
      Stimulations of the different tracts induced variable language disorders that
      were specific to each fiber tract.

PMID- 19747053
TI  - Personal considerations on the history of microneurosurgery.

PMID- 19747054
TI  - Relationship of aggressive monitoring and treatment to improved outcomes in
      severe traumatic brain injury.
AB  - OBJECT: Despite being common practice for decades and being recommended by
      national guidelines, aggressive monitoring and treatment of patients with severe
      traumatic brain injury (TBI) have not been supported by convincing evidence.
      METHODS: The authors reviewed trials and case series reported after 1970 in which
      patients were treated for severe closed TBI, and mortality rates and favorable
      outcomes at 6 months after injury were analyzed. The patient groups were divided
      into those with and without intracranial pressure (ICP) monitoring and intensive
      therapy, and the authors performed a meta-analysis to assess the effects of
      treatment intensity on outcome. RESULTS: Although the mortality rate fell during
      the years reviewed, it was consistently approximately 12% lower among patients in
      the intense treatment group (p < 0.001). Favorable outcomes did not change
      significantly over time, and were 6% higher among the aggressively treated
      patients (p = 0.0105). CONCLUSIONS: Aggressive ICP monitoring and treatment of
      patients with severe TBI is associated with a statistically significant
      improvement in outcome. This improvement occurs independently of temporal
      effects.

PMID- 19747055
TI  - Gamma Knife stereotactic radiosurgery for idiopathic trigeminal neuralgia.
AB  - OBJECT: Trigeminal neuralgia pain causes severe disability. Stereotactic
      radiosurgery is the least invasive surgical option for patients with trigeminal
      neuralgia. Since different medical and surgical options have different rates of
      pain relief and morbidity, it is important to evaluate longer-term outcomes.
      METHODS: The authors retrospectively reviewed outcomes in 503 medically
      refractory patients with trigeminal neuralgia who underwent Gamma Knife surgery
      (GKS). The median patient age was 72 years (range 26-95 years). Prior surgery had
      failed in 205 patients (43%). The GKS typically was performed using MR imaging
      guidance, a single 4-mm isocenter, and a maximum dose of 80 Gy. RESULTS: Patients
      were evaluated for up to 16 years after GKS; 107 patients had > 5 years of follow
      up. Eighty-nine percent of patients achieved initial pain relief that was
      adequate or better, with or without medications (Barrow Neurological Institute
      [BNI] Scores I-IIIb). Significant pain relief (BNI Scores I-IIIa) was achieved in
      73% at 1 year, 65% at 2 years, and 41% at 5 years. Including Score IIIb (pain
      adequately controlled with medication), a BNI score of I-IIIb was found in 80% at
      1 year, 71% at 3 years, 46% at 5 years, and 30% at 10 years. A faster initial
      pain response including adequate and some pain relief was seen in patients with
      trigeminal neuralgia without additional symptoms, patients without prior surgery,
      and patients with a pain duration of < or = 3 years. One hundred ninety-three
      (43%) of 450 patients who achieved initial pain relief reported some recurrent
      pain 3-144 months after initial relief (median 50 months). Factors associated
      with earlier pain recurrence that failed to maintain adequate or some pain relief
      were trigeminal neuralgia with additional symptoms and > or = 3 prior failed
      surgical procedures. Fifty-three patients (10.5%) developed new or increased
      subjective facial paresthesias or numbness and 1 developed deafferentation pain;
      these symptoms resolved in 17 patients. Those who developed sensory loss had
      better long-term pain control (78% at 5 years). CONCLUSIONS: Gamma Knife surgery
      proved to be safe and effective in the treatment of medically refractory
      trigeminal neuralgia and is of value for initial or recurrent pain management.
      Despite the goal of minimizing sensory loss with this procedure, some sensory
      loss may improve long-term outcomes. Pain relapse is amenable to additional GKS
      or another procedure.

PMID- 19747056
TI  - Percutaneous endourologic procedures in high-risk patients in the lateral
      decubitus position under regional anesthesia.
AB  - BACKGROUND AND PURPOSE: The prone position is the most commonly used position for
      percutaneous endourologic procedures. It is usually combined with a general
      anesthesia. In high-risk patients, this approach can lead to circulatory and
      respiratory compromises. Operating on such patients in a full lateral position
      will minimize the hemodynamic and respiratory risks and-if combined with spinal
      anesthesia-will allow for increased patient comfort and safety. PATIENTS AND
      METHODS: After rigorous preoperative assessment, 27 medical high-risk patients
      (12 men) with a mean age of 62 years and an American Society of Anesthesiologists
      score of 3+ were included in this study. The majority (78%) had regional
      anesthesia and were fully awake and alert during the operation. The procedures
      consisted of an initial retrograde renal study/filling with contrast medium with
      the patient in the lithotomy position to aid kidney puncture. The percutaneous
      procedure was then performed with the patient in the lateral decubitus position,
      and access was performed under fluoroscopic and/or ultrasonographic guidance.
      RESULTS: Twenty-two percutaneous nephrolithotomies (PCNL), 3 anterograde
      endopyelotomies (AEP), 1 percutaneous resection of renal pelvic transitional-cell
      carcinoma, and 1 percutaneous renal cyst sclerotization were performed. After
      PCNL, 11 patients were stone free postoperatively, and a further 8 were stone
      free after adjuvant shockwave lithotripsy. Two patients needed temporary Double-J
      stents. One renal access failed. Two procedures were aborted because of
      hemorrhage. One patient died in the recovery room from uncontrollable renal
      bleeding. A renal scan after 3 months showed relief of obstruction in the three
      patients who had undergone AEP. Ultrasonography confirmed complete resolution of
      the sclerotized renal cyst. Neither of the patients with regional anesthesia
      needed conversion to general anesthesia. In two patients who experienced moderate
      pain, a "top-up" with local anesthesia solved the problem. CONCLUSION: The full
      lateral position-while necessitating expertise and some learning for renal
      puncture from an unusual angle-is safe in medical high-risk patients. It can be
      safely performed using regional anesthesia, avoiding the risks of general
      anesthesia and allowing for patient-anesthetist communication throughout the
      procedure. Cardiac and respiratory parameters are improved, stable, and easily
      controlled. As opposed to the supine position, the awake patient is more
      comfortable, and morbid obesity is not a problem.

PMID- 19747057
TI  - Awake endotracheal intubation and prone patient self-positioning: anesthetic and
      positioning considerations during percutaneous nephrolithotomy in obese patients.
AB  - BACKGROUND AND PURPOSE: Obesity is associated with adverse outcomes with certain
      urologic procedures and may make patient positioning more difficult. We describe
      our technique of awake intubation and prone patient self-positioning before
      percutaneous nephrolithotomy (PCNL), and review the literature regarding prone
      positioning in obese patients and the impact of obesity on PCNL. METHODS: Patient
      preparation begins with detailed preoperative counseling regarding the procedure.
      Premedication with a sedative and antisialagogue is followed by airway
      topicalization to suppress gag reflex and pain. Fiberoptic bronchoscope
      intubation is then carried out. The patient then positions himself/herself
      comfortably before induction of general anesthesia. RESULTS: We have successfully
      performed awake intubation and patient prone self-positioning followed by PCNL,
      most recently in a 58-year-old (body mass index 51.3 kg/m(2)) man with a history
      of gastric bypass, diabetes mellitus, and hypertension, without added morbidity.
      Adverse effect on patient cardiopulmonary dynamics can be minimized in the prone
      position. CONCLUSIONS: The technique of awake intubation with prone patient self
      positioning can be helpful for positioning morbidly obese patients before PCNL
      and has been safe and effective in properly selected patients. Efficacy of PCNL
      should not be impacted by obesity or prone positioning and morbidity minimized
      provided that surgical and anesthesia teams understand and safeguard against
      potential complications.

PMID- 19747058
TI  - Management of injury to the bowel during percutaneous stone removal.
AB  - Percutaneous endoscopic renal surgery is usually a safe and effective treatment
      for patients with complex renal calculi, tumors of the collecting system, and
      ureteropelvic junction obstruction. A unique set of complications, however, can
      occur with this surgical approach that may involve the targeted kidney and
      surrounding structures. Bowel injuries represent a very rare complication.
      Methods of preventing colonic and small intestine injuries, diagnosing their
      occurrence, and management strategies are reviewed in this article.

PMID- 19747061
TI  - Threading the needle: getting selenocysteine into proteins.
AB  - The co-translational incorporation of selenocysteine (Sec) requires that UGA be
      recognized as a sense rather than a nonsense codon. This is accomplished by the
      concerted action of a Sec insertion sequence (SECIS) element, SECIS binding
      protein 2, and a ternary complex of the Sec specific elongation factor, Sec
      tRNA(Sec), and GTP. The mechanism by which they alter the canonical protein
      synthesis reaction has been elusive. Here we present an overview of the
      mechanistic perspective on Sec incorporation, highlighting recent advances in the
      field.

PMID- 19747062
TI  - Oxidative stress and vascular smooth muscle cell growth: a mechanistic linkage by
      cyclophilin A.
AB  - Inflammation and oxidative stress contribute to the pathology of many diseases,
      but specific therapeutic targets remain elusive. Oxidative stress, generated by
      excessive reactive oxygen species (ROS), promotes cardiovascular disease.
      However, the precise mechanism of how ROS deteriorate vascular function and
      promote vascular remodeling in vivo has not been clearly elucidated. Cyclophilin
      A (CyPA) is a 20 kD chaperone protein that is secreted from vascular smooth
      muscle cells (VSMC) in response to ROS, and stimulates VSMC proliferation and
      inflammatory cell migration in vitro and in vivo. CyPA (both intracellular and
      extracellular) contributes to inflammation and atherosclerosis by promoting
      endothelial cell (EC) apoptosis and EC expression of leukocyte adhesion
      molecules, stimulating leukocyte migration, enhancing T helper cell type 1 (Th1)
      responses, increasing proliferation of macrophages and vascular smooth muscle
      cells (VSMC), and increasing pro-inflammatory signal transduction in VSMC. We
      tested the hypothesis that CyPA contributes to cardiovascular diseases by
      analyzing several genetic interventions that include the CyPA knockout mouse and
      the CyPA overexpressing transgenic mouse (VSMC-Tg). CyPA plays a crucial role in
      VSMC proliferation/migration and inflammatory cell recruitment, resulting in
      cardiovascular diseases in vivo.

PMID- 19747063
TI  - Prolonged hypoxia increases ROS signaling and RhoA activation in pulmonary artery
      smooth muscle and endothelial cells.
AB  - Phase I of the hypoxic pulmonary vasoconstriction (HPV) response begins upon
      transition to hypoxia and involves an increase in cytosolic calcium
      ([Ca(2+)](i)). Phase II develops during prolonged hypoxia and involves increases
      in constriction without further increases in [Ca(2+)](i), suggesting an increase
      in Ca(2+) sensitivity. Prolonged hypoxia activates RhoA and RhoA kinase, which
      may increase Ca(2+) sensitivity, but the mechanism is unknown. We previously
      found that reactive oxygen species (ROS) trigger Phase I. We therefore asked
      whether ROS generation during prolonged hypoxia activates RhoA in PA smooth
      muscle cells (PASMCs) and endothelial cells (PAECs) during Phase II. By using a
      cytosolic redox sensor, RoGFP, we detected increased oxidant signaling in
      prolonged hypoxia in PASMCs (29.8 +/- 1.3% to 39.8 +/- 1.4%) and PAECs (25.9 +/-
      2.1% to 43.7.9 +/- 3.5%), which was reversed on the return to normoxia and was
      attenuated with EUK-134 in both cell types. RhoA activity increased in PASMCs and
      PAECs during prolonged hypoxia (6.4 +/- 1.2-fold and 5.8 +/- 1.6-fold) and with
      exogenous H(2)O(2) (4.1- and 2.3-fold, respectively). However, abrogation of the
      ROS signal in PASMCs or PAECs with EUK-134 or anoxia failed to attenuate the
      increased RhoA activity. Thus, the ROS signal is sustained during prolonged
      hypoxia in PASMCs and PAECs, and this is sufficient but not required for RhoA
      activation.

PMID- 19747064
TI  - Hypoxia increases ROS signaling and cytosolic Ca(2+) in pulmonary artery smooth
      muscle cells of mouse lungs slices.
AB  - Precapillary arteries constrict during alveolar hypoxia in a response known as
      hypoxic pulmonary vasoconstriction (HPV). The mechanism by which pulmonary
      arterial smooth muscle cells (PASMCs) detect a decrease in Po(2) and trigger
      contraction is not fully understood. Previous studies in cultured PASMCs show
      that hypoxia induces an increase in reactive oxygen species (ROS) production, but
      these results may not reflect responses of PASMCs in their native tissue
      environment. We therefore assessed hypoxia-induced changes in cytosolic ROS in
      PASMCs of precision-cut mouse lung slices expressing the redox-sensitive protein,
      RoGFP. Superfusion of lung slices with hypoxic media (1.5% O(2)) resulted in a
      significant oxidation of RoGFP from normoxic baseline that was attenuated by
      overexpression of cytosolic catalase. Hypoxic superfusion also increased
      [Ca(2+)](i) above normoxic baseline; this response was significantly attenuated
      by cytosolic catalase overexpression or by the administration of EUK134, a
      synthetic SOD-catalase mimetic. The hypoxia-induced increase in [Ca(2+)](i) was
      abolished in the absence of extracellular Ca(2+), indicating that ROS signals
      trigger entry of extracellular calcium. Collectively, these results indicate that
      an increase in cytosolic ROS signaling is required for the increase in
      [Ca(2+)](i) in PASMCs in precision-cut mouse lung slices during the acute HPV
      response.

PMID- 19747065
TI  - Structure-function relations, physiological roles, and evolution of mammalian ER
      resident selenoproteins.
AB  - Selenium is an essential trace element in mammals. The major biological form of
      this micronutrient is the amino acid selenocysteine, which is present in the
      active sites of selenoenzymes. Seven of 25 mammalian selenoproteins have been
      identified as residents of the endoplasmic reticulum, including the 15-kDa
      selenoprotein, type 2 iodothyronine deiodinase and selenoproteins K, M, N, S, and
      T. Most of these proteins are poorly characterized. However, recent studies
      implicate some of them in quality control of protein folding in the ER,
      retrotranslocation of misfolded proteins from the ER to the cytosol, metabolism
      of the thyroid hormone, and regulation of calcium homeostasis. In addition, some
      of these proteins are involved in regulation of glucose metabolism and
      inflammation. This review discusses evolution and structure-function relations of
      the ER-resident selenoproteins and summarizes recent findings on these proteins,
      which reveal the emerging important role of selenium and selenoproteins in ER
      function.

PMID- 19747067
TI  - Modified drug release of poloxamer matrix by including water-soluble and water
      insoluble polymer.
AB  - BACKGROUND: The ability of poloxamer 407 to control drug release was investigated
      along with the effect of incorporation of a second polymer with poloxamer on
      dissolution behavior. METHODS: Tablets made of 30% w/w/ theophylline and 15%,
      25%, 50%, or 69% poloxamer were prepared. Additionally, tablets containing
      mixture of poloxamer with carbomer or hypromellose in a 1:1 ratio and at
      different total levels (15%, 30%, and 50%) were also tested. RESULTS: Data show
      that as the level of poloxamer increased, drug release decreased. Formulations
      containing poloxamer: hypromellose 1:1 at 50% level and formulations containing
      poloxamer: carbomer 1:1 at 30% level produced controlled release matrices over 24
      hours of testing dissolution. The mechanism of drug release follows anomalous
      relaxation non-Fickian diffusion model. CONCLUSIONS: These results suggest that
      the combination of poloxamer 407 with hypromellose or carbomer is feasible and
      has potential to offer the formulator control over drug release.

PMID- 19747066
TI  - The current state of head and neck cancer gene therapy.
AB  - The incidence of head and neck cancer continues to increase worldwide, with
      tobacco exposure and human papillomavirus type 16 infections being the major
      etiological factors. Current therapeutic options are ineffective in approximately
      half of the individuals afflicted with this malignancy. Developments in the
      identification of molecules that sustain head and neck squamous cell carcinoma
      (HNSCC) growth and survival have made molecular targeting by gene therapy
      approaches a feasible therapeutic strategy. Although gene therapy was originally
      designed to correct single gene defects, it has now evolved to encompass all
      forms of therapeutic interventions involving engineered cells and nucleic acids
      that modify the overall pattern of gene expression within target tissues. Several
      preclinical studies and clinical trials have tested the efficacy of targeting
      specific molecules in patients with HNSCC, using genetic therapy approaches. This
      review discusses promising preclinical and clinical approaches and new directions
      for HNSCC gene therapy.

PMID- 19747068
TI  - Simulated food effects on drug release from  ethylcellulose: PVA-PEG graft
      copolymer-coated pellets.
AB  - BACKGROUND: Food effects might substantially alter drug release from oral
      controlled release dosage forms in vivo. METHODS: The robustness of a novel type
      of controlled release film coating was investigated using various types of
      release media and two types of release apparatii. RESULTS: Importantly, none of
      the investigated conditions had a noteworthy impact on the release of freely
      water-soluble diltiazem HCl or slightly water-soluble theophylline from pellets
      coated with ethylcellulose containing small amounts of PVA-PEG graft copolymer.
      In particular, the presence of significant amounts of fats, carbohydrates,
      surfactants, bile salts, and calcium ions in the release medium did not alter
      drug release. Furthermore, changes in the pH and differences in the mechanical
      stress the dosage forms were exposed to did not affect drug release from the
      pellets. CONCLUSION: The investigated film coatings allowing for oral controlled
      drug delivery are highly robust in vitro and likely to be poorly sensitive to
      classical food effects in vivo.

PMID- 19747069
TI  - Exploratory pilot study assessing the risk of cognitive impairment or sedation in
      the elderly following single doses of solifenacin 10 mg.
AB  - OBJECTIVES: To assess the cognitive effects of single doses of solifenacin 10 mg
      compared with placebo (primary objective) and oxybutynin immediate release (IR)
      10 mg (secondary objective) in elderly subjects. METHODS: Single-centre,
      randomised, double-blind, placebo-controlled study in 12 healthy elderly
      volunteers, with three crossover periods separated by two 14-day washout periods.
      Each sequence consisted of a single dose of solifenacin 10 mg in one period,
      oxybutynin IR 10 mg in another and placebo in another. Aspects of attention,
      information processing, working memory, episodic memory and self-rated mood and
      alertness were tested using the validated Cognitive Drug Research computerised
      assessment system. RESULTS: There was no evidence from absolute mean values or
      changes from baseline to suggest that solifenacin 10 mg impaired cognition or
      self-ratings of mood and alertness versus placebo. Post-hoc ANCOVA showed no
      statistically significant cognitive deterioration with solifenacin versus
      placebo, when measured at a time point closest to the probable C(max) of
      solifenacin. Oxybutynin was associated with statistically significant impairments
      in several measures of cognitive function at a time point corresponding with its
      probable C(max). CONCLUSION: In this pilot study, single 10 mg doses of
      solifenacin did not show any clear propensity to impair cognitive function in a
      healthy elderly population.

PMID- 19747070
TI  - Yes we can: a rallying cry!

PMID- 19747071
TI  - Up from crisis: overhauling healthcare information, payment, and delivery in
      extraordinary times. Dialogue with featured speakers from the 6th annual
      connected health symposium.

PMID- 19747072
TI  - The personal health dashboard: consumer electronics is growing in the health and
      wellness market.

PMID- 19747074
TI  - The mammalian aryl hydrocarbon (Ah) receptor: from mediator of dioxin toxicity
      toward physiological functions in skin and liver.
AB  - The mammalian Ah receptor (AhR) is a ligand-activated transcription factor with
      multiple functions in adaptive metabolism, development and dioxin toxicity in a
      variety of organs and cell systems. Phenotypes observed following sustained
      activation by dioxin or in AhR-null mice suggest organ-dependent physiological
      functions. These functions are probably deregulated following exposure to dioxin.
      We focus on skin and liver to facilitate discussion of mechanisms linking
      phenotypes and AhR-modulated genotypes. After a brief summary of currently
      discussed AhR ligand candidates, two groups of direct AhR target genes/proteins
      and associated functions are highlighted: (i) xenobiotic-metabolizing enzymes
      which are also involved in homeostasis of endogenous ligands and (ii) proteins
      controlling cell proliferation/apoptosis, differentiation and inflammation.
      Homeostatic feedback loops might not only include CYP1A1 but also Phase II
      enzymes such as UGT1A1 which controls the antioxidant AhR ligand bilirubin. The
      AhR is involved in extensive crosstalk with other transcription factors and
      multiple signaling pathways. Efforts elucidating the pathway toward
      identification of physiological functions of the AhR remain challenging and
      promising.

PMID- 19747075
TI  - Stimulation of fibroblast proliferation by the plant cysteine protease CMS2MS2 is
      independent of its proteolytic activity and requires ERK activation.
AB  - The cysteine protease CMS2MS2 from Carica candamarcensis latex has been shown to
      enhance proliferation of L929 fibroblast and to activate the extracellular signal
      regulated protein kinase (ERK). In experiments with CMS2MS2 irreversibly
      inhibited by E-64, the proliferative effect on fibroblasts remains unaffected.
      ERK phosphorylation mediated by CMS2MS2 was abolished in the presence of PD 98059
      or U0126, both MAPK cascade inhibitors. In addition, these inhibitors suppress
      the mitogenic activity of intact CMS2MS2 or CMS2MS2-E-64. Furthermore, ERK
      phosphorylation and the mitogenic effect are partially suppressed by a
      phospholipase C (PLC) inhibitor. These data suggest that the mitogenic effect of
      CMS2MS2 on fibroblasts is independent of its proteolytic activity, requires ERK
      phosphorylation, and involves activation of PLC.

PMID- 19747076
TI  - Elafin is specifically inactivated by RgpB from Porphyromonas gingivalis by
      distinct proteolytic cleavage.
AB  - Abstract Porphyromonas gingivalis, the major causative bacterium of
      periodontitis, contributes significantly to elevated proteolytic activity at
      periodontal pockets owing to the presence of both bacteria and host,
      predominantly neutrophil-derived, serine proteases. Normally the activity of the
      latter enzymes is tightly regulated by endogenous proteins, including elafin, a
      potent neutrophil elastase and proteinase 3 inhibitor released from epithelial
      cells at sites of inflammation. Here, we report that all three gingipains (HRgpA,
      RgpB, and Kgp) have the ability to degrade elafin, with RgpB being far more
      efficient than other gingipains. RgpB efficiently inactivates the inhibitory
      activity of elafin at subnanomolar concentrations through proteolysis limited to
      the Arg22-Cys23 peptide bond within the surface loop harboring the inhibitor
      active site. Notably, elafin resists inactivation by several Staphylococcus
      aureus-derived serine and cysteine proteases, confirming the high stability of
      this protein against proteolytic degradation. Therefore, we conclude that elafin
      inactivation by RgpB represents a specific pathogenic adaptation of P. gingivalis
      to disturb the protease-protease inhibitor balance in the infected gingival
      tissue. This contributes to enhanced degradation of host proteins and generation
      of a pool of peptides serving as nutrients for this asaccharolytic pathogen.

PMID- 19747077
TI  - The mechanism of ATP-dependent RNA unwinding by DEAD box proteins.
AB  - DEAD box proteins catalyze the ATP-dependent unwinding of double-stranded RNA
      (dsRNA). In addition, they facilitate protein displacement and remodeling of RNA
      or RNA/protein complexes. Their hallmark feature is local destabilization of RNA
      duplexes. Here, we summarize current data on the DEAD box protein mechanism and
      present a model for RNA unwinding that integrates recent data on the effect of
      ATP analogs and mutations on DEAD box protein activity. DEAD box proteins share a
      conserved helicase core with two flexibly linked RecA-like domains that contain
      all helicase signature motifs. Variable flanking regions contribute to substrate
      binding and modulate activity. In the presence of ATP and RNA, the helicase core
      adopts a compact, closed conformation with extensive interdomain contacts and
      high affinity for RNA. In the closed conformation, the RecA-like domains form a
      catalytic site for ATP hydrolysis and a continuous RNA binding site. A kink in
      the backbone of the bound RNA locally destabilizes the duplex. Rearrangement of
      this initial complex generates a hydrolysis- and unwinding-competent state. From
      this complex, the first RNA strand can dissociate. After ATP hydrolysis and
      phosphate release, the DEAD box protein returns to a low-affinity state for RNA.
      Dissociation of the second RNA strand and reopening of the cleft in the helicase
      core allow for further catalytic cycles.

PMID- 19747078
TI  - Memory and neural networks on the basis of color centers in solids.
AB  - Optical data recording is one of the most widely used and efficient systems of
      memory in the non-living world. The application of color centers in this context
      offers not only systems of high speed in writing and read-out due to a high
      degree of parallelism in data handling but also a possibility to set up models of
      neural networks. In this way, systems with a high potential for image processing,
      pattern recognition and logical operations can be constructed. A limitation to
      storage density is given by the diffraction limit of optical data recording. It
      is shown that this limitation can at least in principle be overcome by the
      principle of spectral hole burning, which results in systems of storage
      capacities close to the human brain system.

PMID- 19747079
TI  - Protein carboxyl methylation and the biochemistry of memory.
AB  - Bacterial chemotaxis is mediated by two reversible protein modification
      chemistries: phosphorylation and carboxyl methylation. Attractants bind to
      membrane chemoreceptors that control the activity of a protein kinase which acts
      in turn to control flagellar motor activity. Coordinate changes in receptor
      carboxyl methylation provide a negative feedback mechanism that serves a memory
      function. Protein carboxyl methylation might play an analogous role in the
      nervous system. Two protein carboxyl methyltransferases serve to regulate signal
      transduction pathways in eukaryotic cells. One is highly expressed in the
      Purkinje layer of the cerebellum where it methyl esterifies prenylated cysteine
      residues at the carboxyl-termini of Ras-related and heterotrimeric G-proteins.
      The other is abundant throughout the brain where it methylates the carboxyl
      terminus of protein phosphatase 2A. The phosphatase methyltransferase and the
      protein methylesterase that reverses phosphatase methylation are structurally
      related to the corresponding bacterial chemotaxis methylating and demethylating
      enzymes. Recent results indicate that deficiencies in phosphatase methylation
      play an important role in the etiology of Alzheimer's disease.

PMID- 19747080
TI  - Mechanistic insights in light-induced cAMP production by photoactivated adenylyl
      cyclase alpha (PACalpha).
AB  - The flagellate Euglena gracilis contains as photoreceptor complex a
      heterotetrameric light-sensitive adenylyl cyclase (AC), consisting of the
      flavoproteins PACalpha and PACbeta. Previously, we demonstrated the functional
      expression of PACalpha and PACbeta in oocytes from Xenopus laevis and of PACalpha
      in different animal cell types. Both yielded a blue light-induced increase of
      cellular [cAMP]. Here, we report that the action spectrum of PACalpha is
      flavoprotein-typical, with maxima at approximately 380 and approximately 470 nm.
      Mutational analysis of PACalpha yields a model for its structure and function.
      PACalpha shows a basal AC activity in the dark which is unaffected by mutating
      the conserved tyrosines in the two flavin-binding domains (F1, F2), Y60 in F1 and
      Y472 in F2. Y60 in F1 is, however, essential for photoactivation as light
      stimulation of cyclase activity is completely lost in the F1 mutant Y60F. This
      effect does not occur in the respective mutation in F2 (Y472F). Mutating the two
      cyclase domains (C1, C2) indicated that C1 and C2 form a heterodimeric catalytic
      center as in mammalian class III cyclases. Interaction of C1 with C2 in the same
      molecule could be excluded as coexpression of non-functional C1 and C2 mutants
      restored light-induced cyclase activity. Our results strongly suggest an
      intermolecular dimerization of C1 and C2 domains on PACalpha for a functional
      enzyme.

PMID- 19747081
TI  - The epigenetic bottleneck of neurodegenerative and psychiatric diseases.
AB  - The orchestrated expression of genes is essential for the development and
      survival of every organism. In addition to the role of transcription factors, the
      availability of genes for transcription is controlled by a series of proteins
      that regulate epigenetic chromatin remodeling. The two most studied epigenetic
      phenomena are DNA methylation and histone-tail modifications. Although a large
      body of literature implicates the deregulation of histone acetylation and DNA
      methylation with the pathogenesis of cancer, recently epigenetic mechanisms have
      also gained much attention in the neuroscientific community. In fact, a new field
      of research is rapidly emerging and there is now accumulating evidence that the
      molecular machinery that regulates histone acetylation and DNA methylation is
      intimately involved in synaptic plasticity and is essential for learning and
      memory. Importantly, dysfunction of epigenetic gene expression in the brain might
      be involved in neurodegenerative and psychiatric diseases. In particular, it was
      found that inhibition of histone deacetylases attenuates synaptic and neuronal
      loss in animal models for various neurodegenerative diseases and improves
      cognitive function. In this article, we will summarize recent data in the novel
      field of neuroepigenetics and discuss the question why epigenetic strategies are
      suitable therapeutic approaches for the treatment of brain diseases.

PMID- 19747082
TI  - Chemotaxis: how bacteria use memory.
AB  - Bacterial chemotaxis represents one of the simplest and best studied examples of
      unicellular behavior. Chemotaxis allows swimming bacterial cells to follow
      chemical gradients in the environment by performing temporal comparisons of
      ligand concentrations. The process of chemotaxis in the model bacterium
      Escherichia coli has been studied in great molecular detail over the past 40
      years, using a large range of experimental tools to investigate physiology,
      genetics and biochemistry of the system. The abundance of quantitative
      experimental data enabled detailed computational modeling of the pathway and
      theoretical analyses of such properties as robustness and signal amplification.
      Because of the temporal mode of gradient sensing in bacterial chemotaxis,
      molecular memory is an essential component of the chemotaxis pathway. Recent
      studies suggest that the memory time scale has been evolutionary optimized to
      perform optimal comparisons of stimuli while swimming in the gradient. Moreover,
      noise in the adaptation system, which results from variations of the adaptation
      rate both over time and among cells, might be beneficial for the overall
      chemotactic performance of the population.

PMID- 19747083
TI  - Balance of power--dynamic regulation of chromatin in plant development.
AB  - Chromatin states profoundly determine and maintain gene activity and gene
      repression in eukaryotic organisms. Regulation of chromatin involves chromatin
      remodeling, chromatin modifications and exchange of chromatin components and is
      linked to DNA methylation in some cases. In plants and other organisms, chromatin
      proteins control many developmental pathways, integrate changes in the
      environment and can confer a cellular memory of these cues. Here, we review the
      molecular mechanisms that provide a dynamic regulation of chromatin in a cell. In
      addition, we discuss how chromatin needs to be flexibly regulated during plant
      growth to confer stable expression states that can occasionally be reset, e.g.,
      owing to changes in the environment and progression of development.

PMID- 19747084
TI  - Investigating the role of PDGF as a potential drug therapy in bone formation and
      fracture healing.
AB  - BACKGROUND: Platelet-derived growth factor (PDGF) has been shown in vivo to
      increase bone formation and supplement fracture healing, and may have a role as a
      therapeutic agent in the treatment of bone loss and fracture healing in humans.
      OBJECTIVE: A comprehensive review of the recent literature on the effect of PDGF
      on bone mineral density and fracture healing. METHODS: In vitro and in vivo
      evidence was systematically collected using medical search engines MEDLINE/OVID
      (1950 to March 2008) and EMBASE (1980 to March 2008) databases.
      RESULTS/CONCLUSION: Evidence to date suggests that PDGF-BB, and to a lesser
      extent PDGF-AA, may have potential therapeutic use in the treatment of
      osteoporosis and bone healing in humans. Additionally, by targeting alpha
      receptors on osteoblasts, a potential anabolic effect on bone metabolism in
      humans can be anticipated; however, more research needs to be done to assess the
      role of beta-receptors in human bone.

PMID- 19747085
TI  - Construction of covalently coupled, concatameric dimers of 7TM receptors.
AB  - 7TM receptors are easily fused to proteins such as G proteins and arrestin but
      because of the fact that their terminals are found on each side of the membrane
      they cannot be joined directly in covalent dimers. Here, we use an artificial
      connector comprising a transmembrane helix composed of Leu-Ala repeats flanked by
      flexible spacers and positively charged residues to ensure correct inside-out
      orientation plus an extracellular HA-tag to construct covalently coupled dimers
      of 7TM receptors. Such 15 TM concatameric homo- and heterodimers of the beta(2)
      adrenergic and the NK(1) receptors, which normally do not dimerize with each
      other, were expressed surprisingly well at the cell surface, where they bound
      ligands and activated signal transduction in a manner rather similar to the
      corresponding wild-type receptors. The concatameric heterodimers internalized
      upon stimulation with agonists for either of the protomers, which was not
      observed upon simple coexpression of the two receptors. It is concluded that
      covalently joined 7TM receptor dimers with surprisingly normal receptor
      properties can be constructed with use of an artificial transmembrane connector,
      which perhaps can be used to fuse other membrane proteins.

PMID- 19747086
TI  - Determination of tobacco-specific N-nitrosamines in urine of smokers and non
      smokers.
AB  - Tobacco-specific N-nitrosamines (TSNA) include 4-(methylnitrosamino)-1-(3
      pyridyl)-1-butanone (NNK), N'-nitrosonornicotine (NNN), N'-nitrosoanabasine (NAB)
      and N'-nitrosoanatabine (NAT) and are found in tobacco and tobacco smoke. TSNA
      are of interest for biomonitoring of tobacco-smoke exposure as they are
      associated with carcinogenesis. Both NNK and NNN are classified by IARC as Group
      1 carcinogens. Samples of 24 h urine collections (n = 108) were analysed from
      smokers and non-smokers, using a newly developed and validated LC-MS/MS method
      for determining total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL, the
      major metabolite of NNK), and total NNN, NAB and NAT. TSNA levels in smokers'
      urine were significantly higher than in non-smokers. In smokers, urinary
      excretion of total TSNA correlated significantly (r > 0.5) with markers of
      smoking dose, such as daily cigarette consumption, salivary cotinine and urinary
      nicotine equivalents and increased with the ISO tar yield of cigarettes smoked.
      The correlation between urinary total NNN and the smoking dose was weaker (r =
      0.4-0.5). In conclusion, this new method is suitable for assessing tobacco use
      related exposure to NNK, NNN, NAB and NAT.

PMID- 19747087
TI  - Evaluation of phagocytic activity and nitric oxide generation by molluscan
      haemocytes as biomarkers of inorganic arsenic exposure.
AB  - The natural habitats of the freshwater bivalve Lamellidens marginalis face the
      risk of contamination by the toxic metalloid arsenic. Haemocyte-mediated non-self
      phagocytosis and generation of nitric oxide (NO) as reactive nitrogen
      intermediate were examined to establish the reliability of the parameters as
      biomarkers of sodium arsenite-induced stress on the animal at sublethal
      concentrations. The studies suggest imposition of a remarkable immune
      compromise/immune suppression on the animal by the natural contaminant. The
      animal expressed partial recovery in its phagocytic potential and NO generation
      over a period of 30 days. Quantitation of phagocytic efficiency and
      intrahaemocyte NO generation indicates the possibility of the parameters be
      accepted as cellular biomarkers to estimate and characterize the vulnerability of
      the freshwater organisms to sodium arsenite-induced stress.

PMID- 19747088
TI  - An investigation into the potential use of serum Hsp70  as a novel tumour
      biomarker for Hsp90 inhibitors.
AB  - Hsp90 inhibitors are under investigation in multiple human clinical trials for
      the treatment of cancers, including myeloma, breast cancer, prostate, lung,
      melanoma, gastrointestinal stromal tumour and acute myeloid leukaemia. The
      pharmacodynamic activity of Hsp90 inhibitors in the clinic is currently assessed
      by Hsp70 induction in peripheral blood mononuclear cells using Western blot
      analysis, a method that is laborious, semiquantitative and difficult to implement
      in the clinic. Since Hsp70 was reported to be secreted by tumour cells and
      elevated in sera of cancer patients, serum Hsp70 has been evaluated as a
      potentially more robust, easily and reproducibly measured biomarker of Hsp90
      inhibition as an alternative to cytosolic Hsp70. A highly sensitive and specific
      electrochemiluminescent ELISA was developed to measure serum Hsp70 and employed
      to evaluate Hsp70 levels in both ex vivo and xenograft samples. In ex vivo
      studies, maximal secretion of Hsp70 by tumour cells was observed between 48 and
      72 h after exposure to Hsp90 inhibitors. In in vivo studies a 3-4-fold increase
      in serum Hsp70 was observed following treatment with BIIB021 in tumour-bearing
      mice. Strikingly, secreted Hsp70 was detectable in mice transplanted with human
      tumours but not in naive mice indicating a direct origination from the
      transplanted tumours. Analysis of clinical samples revealed low baseline levels
      (2 - 15 ng ml(-1)) of Hsp70 in the serum of cancer patients and normal donors.
      Together these findings in laboratory studies and archived cancer patient sera
      suggest that serum Hsp70 could be a novel biomarker to assess reliably the
      pharmacological effects of Hsp90 inhibitors in clinical trials, especially under
      conditions where collection of tumour biopsies is not feasible.

PMID- 19747089
TI  - Function of SIRT1 in physiology.
AB  - Sirtuins were originally defined as a family of oxidized nicotinamide adenine
      nucleotide (NAD+)-dependent enzymes that deacetylate lysine residues on various
      proteins. The sirtuins are remarkably conserved throughout evolution from archae
      to eukaryotes. They were named after their homology to the Saccharomyces
      cerevisiae gene silent information regulator 2 (Sir2). The mammalian sirtuins,
      SIRT1-7, are implicated in a variety of cellular functions ranging from gene
      silencing, control of the cell cycle and apoptosis, and energy homeostasis. As
      SIRT1 is a nuclear protein and is the mammalian homolog most highly related to
      Sir2, it has been the focus of a large number of recent studies. Here we review
      some of the current data related to SIRT1 and discuss its mode of action and
      biological role in cellular and organismal models.

PMID- 19747090
TI  - Purification and biochemical characterization of a D-galactose binding lectin
      from Japanese sea hare (Aplysia kurodai) eggs.
AB  - A lectin was purified from Japanese sea hare Aplysia kurodai by lactosyl-agarose
      affinity chromatography. The molecular mass of the lectin was determined to be 56
      and 32 kDa by SDS-PAGE under non-reducing and reducing conditions, respectively.
      It was found to agglutinate trypsinized and glutaraldehyde-fixed rabbit and human
      erythrocytes in the absence of divalent cations. The lectin exhibited stable
      thermo-tolerance as it retained hemagglutinating activity for 1 h even at 80
      degrees C and showed stability at pH 10. By contrast, it was very sensitive at pH
      less than 5 and in the presence of the sulfhydryl-group preserving reagent, beta
      mercaptoethanol. The hemagglutinating activity by the lectin was specifically
      inhibited by D-galactose, galacturonic acid, methyl-alpha- and methyl-beta-D
      galactopyranoside, lactose, melibiose, and asialofetuin. The association rate
      constant (k(ass)) and dissociation rate constant (k(diss)) were determined for
      the lectin to be 4.3 x 10(5) M(-1) x sec(-1) and 2.2 x 10(-3) sec(-1),
      respectively, using a surface plasmon resonance biosensor. The lectin moderately
      inhibited cell proliferation in the P388 cell line dose dependently.
      Interestingly, lectin-treated cells did not show a fragmented DNA ladder as is
      caused by apoptosis, suggesting that the cell proliferation inhibition was caused
      by another unknown mechanism.

PMID- 19747091
TI  - Molecular characterization of tumor associated glyceraldehyde-3-phosphate
      dehydrogenase.
AB  - Here we describe the purification of glyceraldehyde-3-phosphate dehydrogenase
      (GAPDH) from normal leukocytes of healthy subjects and leukocytes of chronic
      myeloid leukemia (CML) patients and from normal mouse muscle and sarcoma tissue.
      The data indicate that some properties of GAPDH of leukocytes of CML patients and
      sarcoma tissues are similar and also similar to those of EAC (Ehrlich ascites
      carcinoma) cellular GAPDH but distinctly different from those of the normal
      cellular GAPDH. Polyclonal antiserum raised against the 54 kDa subunit of EAC
      cell GAPDH strongly reacted with GAPDH of leukocytes of CML patients and sarcoma
      tissue GAPDH only and weakly reacted with GAPDH of normal leukocyte and normal
      muscle and a variety of other tissues of normal rats. Both the subunits of GAPDH
      of sarcoma tissues were partially sequenced from the N-terminus and compared with
      the known sequences of GAPDH. The altered properties of GAPDH of three different
      malignant sources might be common feature of all malignant cells, which is
      discussed in relation to glycolysis and malignant aberrations.

PMID- 19747092
TI  - Identification and mapping of ten new potential insulators in the FXYD5-COX7A1
      region of human chromosome 19q13.12.
AB  - A positive-negative selection system revealed 10 potential insulators able to
      block enhancer interaction with promoter in the 10(6) bp human chromosome 19
      region between genes FXYD5 and COX7A1. Relative positions of insulators and genes
      are in accord with the hypothesis that insulators subdivide genomic DNA into
      independently regulated loop domains.

PMID- 19747093
TI  - Structural and kinetic features of family I inorganic pyrophosphatase from Vibrio
      cholerae.
AB  - In this paper, kinetic properties of a soluble inorganic pyrophosphatase of
      family I from Vibrio cholerae (V-PPase), intestinal pathogen and causative agent
      of human cholera, are characterized in detail, and the crystal structure of a
      metal-free enzyme is reported. Hydrolytic activity of V-PPase has been studied as
      a function of pH, concentration of metal cofactors (Mg2+ or Mn2+), and ionic
      strength. It has been found that, despite the high conservation of amino acid
      sequences for the known bacterial PPases of family I, V-PPase differs from the
      other enzymes of the same family in a number of parameters. Dissociation
      constants of V-PPase complexed with Mg2+ or Mn2+ were essentially the same as for
      Escherichia coli PPase (E-PPase). However, the pH optimum of MgPP(i) hydrolysis
      by V-PPase was shifted to more alkaline pH due to higher values of the pK(a) of
      ionizable groups for both the free enzyme and the enzyme-substrate complex. The
      stability of a hexameric form of V-PPase has been studied as a function of pH.
      The corresponding pK(a) of a group that controls the stability of the hexamer at
      pH below 6 (pK(a) = 4.4) was significantly lower than in the other hexameric
      PPases. The crystal structure reported here is analyzed and compared with the
      structure of E-PPase. The location of amino acid residues that differ in V-PPase
      and E-PPase is discussed. Since V-PPase has been found to retain its hydrolytic
      activity in high ionic strength media, the observed structural and kinetic
      features are analyzed in view of the possible osmoadaptation of this protein.

PMID- 19747094
TI  - Cloning and characterization of NAD-dependent protein deacetylase (Rv1151c) from
      Mycobacterium tuberculosis.
AB  - Sir2 family proteins are highly conserved and catalyze a well-characterized NAD
      dependent protein deacetylation reaction that regulates multiple cellular
      processes including aging, gene silencing, cellular differentiation, and
      metabolic pathways. Little is known about Sir2 family proteins in bacteria. The
      Sir2 homolog Rv1151c of Mycobacterium tuberculosis was cloned and over-expressed
      in Escherichia coli, and the protein then purified by Ni(2+)-affinity
      chromatography to homogeneity. The purified recombinant protein showed a typical
      NAD-dependent protein deacetylase activity that could be inhibited by
      nicotinamide and other known Sir2 inhibitors. The optimal temperature and pH for
      activity of Rv1151c are 25 degrees C and pH 9 +/- 1, respectively. Rv1151c is
      capable of deacetylating the acetyl-CoA synthetase from M. tuberculosis. However,
      unlike Sir2 family proteins identified from other bacteria, Rv1151c shows a
      substrate-independent NAD glycohydrolase activity in accordance with its auto-ADP
      ribosylation activity.

PMID- 19747095
TI  - Telomerase from yeast Saccharomyces cerevisiae is active in vitro as a monomer.
AB  - A system for isolation of yeast telomerase via RNA affinity tag in TLC1 RNA was
      developed. Streptavidin aptamer was inserted at two different positions in TLC1
      RNA. Telomerase with TLC1 RNA with one of these inserts is functional in vivo and
      can be isolated by affinity chromatography in vitro. A telomerase preparation
      isolated using this technique from a strain producing two distinguishable TLC1
      RNA molecules (with and without aptameric insertion) resulted in isolation of
      active telomerase containing only TLC1 RNA with the aptamer. Our results indicate
      that yeast telomerase is active in vitro as a monomer.

PMID- 19747096
TI  - Lipid-protein nanodiscs: possible application in high-resolution NMR
      investigations of membrane proteins and membrane-active peptides.
AB  - High-resolution NMR is shown to be applicable for investigation of membrane
      proteins and membrane-active peptides embedded into lipid-protein nanodiscs
      (LPNs). (15)N-Labeled K+-channel from Streptomyces lividans (KcsA) and the
      antibiotic antiamoebin I from Emericellopsis minima (Aam-I) were embedded in LPNs
      of different lipid composition. Formation of stable complexes undergoing
      isotropic motion in solution was confirmed by size-exclusion chromatography and
      (31)P-NMR spectroscopy. The 2D 1H-(15)N-correlation spectra were recorded for
      KcsA in the complex with LPN containing DMPC and for Aam-I in LPNs based on DOPG,
      DLPC, DMPC, and POPC. The spectra recorded were compared with those in detergent
      containing micelles and small bicelles commonly used in high-resolution NMR
      spectroscopy of membrane proteins. The spectra recorded in LPN environments
      demonstrated similar signal dispersion but significantly increased (1)H(N) line
      width. The spectra of Aam-I embedded in LPNs containing phosphatidylcholine
      showed significant selective line broadening, thus suggesting exchange
      process(es) between several membrane-bound states of the peptide. (15)N
      relaxation rates were measured to obtain the effective rotational correlation
      time of the Aam-I molecule. The obtained value (approximately 40 nsec at 45
      degrees C) is indicative of additional peptide motions within the Aam-I/LPN
      complex.

PMID- 19747097
TI  - Effect of exogenous phenols on superoxide production by extracellular peroxidase
      from wheat seedling roots.
AB  - Competitive and complimentary relationships of various peroxidase substrates were
      studied to elucidate the enzymatic mechanisms underlying production of reactive
      oxygen species in plant cell apoplast. Dianisidine peroxidase released from wheat
      seedling roots was inhibited by ferulate and coniferol, while ferulic and
      coniferyl peroxidases were activated by o-dianisidine. Both ferulate and
      coniferol, when added together with hydrogen peroxide, stimulated superoxide
      production by extracellular peroxidase. We suggest that substrate-substrate
      activation of extracellular peroxidases is important for stress-induced oxidative
      burst in plant cells.

PMID- 19747098
TI  - Interaction of pyrophosphate with catalytic and noncatalytic sites of chloroplast
      ATP synthase.
AB  - The effect of pyrophosphate (PP(i)) on labeled nucleotide incorporation into
      noncatalytic sites of chloroplast ATP synthase was studied. In illuminated
      thylakoid membranes, PP(i) competed with nucleotides for binding to noncatalytic
      sites. In the dark, PP(i) was capable of tight binding to noncatalytic sites
      previously vacated by endogenous nucleotides, thereby preventing their subsequent
      interaction with ADP and ATP. The effect of PP(i) on ATP hydrolysis kinetics was
      also elucidated. In the dark at micromolar ATP concentrations, PP(i) inhibited
      ATPase activity of ATP synthase. Addition of PP(i) to the reaction mixture at the
      step of preliminary illumination inhibited high initial activity of the enzyme,
      but stimulated its activity during prolonged incubation. These results indicate
      that the stimulating effect of PP(i) light preincubation with thylakoid membranes
      on ATPase activity is caused by its binding to ATP synthase noncatalytic sites.
      The inhibition of ATP synthase results from competition between PP(i) and ATP for
      binding to catalytic sites.

PMID- 19747099
TI  - Purification, characterization and kinetics of thiol protease inhibitor from goat
      (Capra hircus) lung.
AB  - In the present study, two molecular forms of goat lung cystatin (GLC), I and II,
      were purified to homogeneity by a two-step procedure including ammonium sulfate
      precipitation (40-60%) and ion exchange chromatography. The inhibitor forms
      migrated as single bands under native and SDS-PAGE with and without reducing
      agent giving molecular mass of 66.4 and 76.4 kDa, respectively. GLC-I possesses
      0.07% and GLC-II 2.3% carbohydrate content and no -SH groups. GLC-I showed
      greater affinity for papain than for ficin and bromelain. Immunological studies
      showed that the inhibitor was pure and there was cross reactivity between anti
      GLC-I serum and goat brain cystatin. Both inhibitor forms were stable in the pH
      range of 3-10 and up to 75 degrees C. GLC-I was found to possess 49% alpha
      helical structure by CD spectroscopy. The inhibitor-papain complexes showed
      conformational changes as invoked by UV and fluorescence spectroscopic studies.

PMID- 19747100
TI  - Cooperative binding of substrates to transketolase from Saccharomyces cerevisiae.
AB  - Catalytic activity of two active sites of transketolase and their affinity
      towards the substrates (xylulose-5-phosphate and ribose-5-phosphate) has been
      studied in the presence of Ca2+ and Mg2+. In the presence of Ca2+, the active
      sites exhibit negative cooperativity in binding both xylulose-5-phosphate (donor
      substrate) and ribose-5-phosphate (acceptor substrate) and positive cooperativity
      in the catalytic transformation of the substrates. In the presence of Mg2+,
      nonequivalence of the active sites is not observed.

PMID- 19747101
TI  - Features of structural organization and expression regulation of malate
      dehydrogenase isoforms from Rhodobacter sphaeroides strain 2R.
AB  - Two isoforms of malate dehydrogenase (MDH), dimeric and tetrameric, have been
      found in the purple non-sulfur bacterium Rhodobacter sphaeroides strain 2R,
      devoid of the glyoxylate shunt, which assimilate acetate via the citramalate
      cycle. Inhibitory analysis showed that the 74-kDa protein is involved in
      tricarboxylic acid cycle, while the 148-kDa MDH takes part in the citramalate
      pathway. A single gene encoding synthesis of the isologous subunits of the MDH
      isoforms was found during molecular-biological investigations. The appearance in
      the studied bacterium of the tetrameric MDH isoform during growth in the presence
      of acetate is probably due to the increased level of mdh gene expression,
      revealed by the real-time PCR, the product of which in cooperation with the
      citramalate cycle enzymes plays an important role in acetate assimilation.

PMID- 19747102
TI  - Purification and characterization of pectin lyase secreted by Penicillium
      citrinum.
AB  - The importance of various parameters such as sugarcane juice concentration, pH of
      the medium, and effects of different solid supports for maximum secretion of
      pectin lyase from Penicillium citrinum MTCC 8897 has been studied. The enzyme was
      purified to homogeneity by Sephadex G-100 and DEAE-cellulose chromatography. The
      molecular mass determined by SDS-PAGE was 31 kDa. The K(m) and k(cat) values were
      found to be 1 mg/ml and 76 sec(-1), respectively. The optimum pH of the purified
      pectin lyase was 9.0, though it retains activity in the pH 9.0-12.0 range when
      exposed for 24 h. The optimum temperature was 50 degrees C, and the pectin lyase
      was found to be completely stable up to 40 degrees C when exposed for 1 h. The
      purified pectin lyase was found efficient in retting of Linum usitatissimum,
      Cannabis sativa, and Crotalaria juncea.

PMID- 19747103
TI  - Characteristics of light-harvesting complex II mutant of Rhodobacter sphaeroides
      with alterations at the transmembrane helices of beta-subunit.
AB  - The peripheral light-harvesting complex II (LHII) is an important component of
      the photosynthetic apparatus of Rhodobacter sphaeroides. In this study, genetic,
      biochemical, and spectroscopic approaches were applied to investigate the
      spectral properties and functions of LHII in which two amino acid residues Phe32
      and Leu42 in the transmembrane helix domain of pucB-encoded beta-apoprotein were
      replaced by Leu and Pro. The mutated LHII complex showed blue shift of absorbance
      peaks in the near infrared region at approximately 801-845 nm in R. sphaeroides.
      It should be noted that the B800 peak was much lower than that of the native
      LHII, and transfer energy was efficient from the B800 to the B850 pigments in the
      LHII complex. The results suggest that the mutated pucB could be expressed in R.
      sphaeroides, and the functional LHII was assembled into the membrane of R.
      sphaeroides notwithstanding with the different spectral properties. These mutated
      residues were indeed critical for the modulation of characteristics and function
      of LHII complex.

PMID- 19747104
TI  - Study of the inhibitory effect of fatty acids on the interaction between DNA and
      polymerase beta.
AB  - The binding of human DNA polymerase beta (pol beta) to DNA template-primer duplex
      and single-stranded DNA in the absence or presence of pol beta inhibitors has
      been studied using a surface plasmon resonance biosensor. Two fatty acids,
      linoleic acid and nervonic acid, were used as potent pol beta inhibitors. In the
      interaction between pol beta and DNA, pol beta could bind to ssDNA in a single
      binding mode, but bound to DNA template-primer duplexes in a parallel mode. Both
      pol beta inhibitors prevented the binding of pol beta to the single strand
      overhang and changed the binding from parallel to single mode. The affinities of
      pol beta to the template-primer duplex region in the presence of nervonic acid or
      linoleic acid were decreased by 20 and 5 times, respectively. The significant
      inhibitory effect of nervonic acid on the pol beta-duplex interaction was due to
      both a 2-fold decrease in the association rate and a 9-fold increase in the
      dissociation rate. In the presence of linoleic acid, no significant change of
      association rate was observed, and the decrease in binding affinity of pol beta
      to DNA was mainly due to 7-fold increase in the dissociation rate.

PMID- 19747107
TI  - Unravelling the role of infectious agents in the pathogenesis of human
      autoimmunity: the hypothesis of the retroviral involvement revisited.
AB  - The incidence of autoimmune disorders is increasing worldwide. Several theories
      have been proposed to explain how the breakdown in the balance between
      autoregulatory immune pathways and pathogenic autoreactivity generate
      autoimmunity. On the basis of a large body of epidemiological, clinical and
      experimental evidence, it has been suggested that an unfortunate interplay of
      genetic susceptibility and environmental factors must play an important role in
      generating the abnormal autoimmune response. Although genetic factors have been
      well dissected, the environmental agents, that may be causative of disease are
      still under investigation. Their discovery is obviously relevant because they
      enable us to device preventive and therapeutic strategies in trying to halt the
      progress and ultimately treat this category of disorders. Among the environmental
      factors, infectious agents have been proposed as the best candidate triggers in
      the autoimmune pathogenesis. The observation that a long preclinical period often
      precedes the clinical onset of disease, in analogy to the clinical symptoms of
      AIDS, led to propose exogenous and endogenous retroviruses as suspected culprits
      for organ and non-organ specific autoimmune disorders. The hypothesis is
      revisited in this article in the light of our research experience over the past
      years and of relevant literature emerging in the field.

PMID- 19747110
TI  - Overview of the molecular bases of resistance to chemotherapy in liver and
      gastrointestinal tumours.
AB  - Primary malignancies of the liver and the gastrointestinal tract constitute one
      of the main health problems worldwide. Together, these types of tumour are the
      first cause of death due to cancer, followed by lung and breast cancer
      respectively. One important limitation in the treatment of these tumours is that,
      with a few exceptions, they exhibit marked resistance to currently available
      drugs. Moreover, most of them develop chemoresistance during treatment. The
      mechanisms responsible for drug refractoriness in gastrointestinal tumours
      include a reduction in drug uptake; enhanced drug export; intracellular
      inactivation of the effective agent; alteration of the molecular target; an
      increase in the activity of the target route to be inhibited or the appearance or
      stimulation of alternative routes; enhanced repair of drug-induced modifications
      in the target molecules, and the activation/inhibition of intracellular
      signalling pathways, which leads to a negative balance between the
      apoptosis/survival of tumour cells. A better understanding of these mechanisms is
      needed in order to develop accurate tests to predict the lack of response to
      chemotherapy and novel approaches aimed at overcoming resistance to anticancer
      agents. The purpose of the present review is to offer an updated overview of the
      molecular mechanisms of resistance to cytostatic drugs in the most frequent types
      of primary malignant tumour affecting the liver and gastrointestinal tract.

PMID- 19747111
TI  - Medulloblastoma: role of developmental pathways, DNA repair signaling, and other
      players.
AB  - Medulloblastoma is a cerebellar tumor affecting children and young adults, and
      accounts for approximately one fifth of all pediatric brain tumors. Despite
      multimodal therapy that includes surgery, radiotherapy and chemotherapy,
      recurrence is frequent and overall mortality rate remains relatively high.
      Moreover, radiation therapy results in severe effects on intellect, and younger
      age of treatment correlates with larger deficits. Improvements in therapy of this
      childhood tumor will focus increasingly on the clarification of the exact
      cellular origin and the genetic mechanisms contributing to tumor formation, and
      on new targeted therapeutic options. Aberrant activation of the Hedgehog (Hh) and
      Wnt developmental pathways is associated with medulloblastoma, but deregulation
      of other molecular pathways, including insulin-like growth factor (IGF)
      signaling, has also been implicated in the pathogenesis of the tumor. Recent
      observations in mouse models have demonstrated the importance of genome
      surveillance, as defects in DNA repair pathways in animals can lead to genomic
      instability in neural progenitor cells, resulting in medulloblastoma. The current
      review will focus on the most recent findings on the molecular pathology of
      medulloblastoma and discuss their potential contribution to treatments directed
      by the molecular alterations.

PMID- 19747113
TI  - Multiplexed fluorescence imaging of tumor biomarkers in gene expression and
      protein levels for personalized and predictive medicine.
AB  - Combining groundbreaking research and developments in cancer biomarkers,
      nanotechnology and molecular targeted medicine, a new realm of therapy is
      possible: personalized and predictive medicine. Developing a method to detect the
      overexpression of several tumor marker genes simultaneously, knowing that a
      single cell generally expresses more than one altered gene, should have a high
      predictive value for identifying cancer cells amidst the normal cellular
      background. Theoretically, a cancer's unique molecular profile can be used to
      predict its invasive and metastatic potential, its ability to evade immune
      surveillance, and its potential response to treatment. Fluorescent probes have
      been developed to detect the levels of expression of various biomarkers in tumor
      cells and tissues. Expression of biomarker messenger RNAs (mRNAs) or the presence
      of a specific mutation in an oncogene in cancer cells can be detected using
      molecular beacons (MBs) that only emit fluorescent signals after binding to its
      specific target mRNAs. Antibodies or ligands labeled with fluorophores or
      fluorescent quantum dots (QDs) have been successfully used to identify specific
      proteins expressed in cells. Furthermore, multiplex imaging using both MBs and
      antibodies labeled with a fluorescent probe on the same sample may provide
      important information correlating the level of mRNA expression and the subsequent
      level of protein production for a given biomarker. This technology will be useful
      in research investigating cancer biology, molecular imaging and molecular
      profiling. With the identification of biomarkers that are related to aggressive
      tumor types, we may be able to predict within certain patient populations who
      will develop invasive cancers, and what their prognosis will be given different
      treatment modalities, ultimately delivering medical care and treatment strategies
      that are specifically tailored to each individual patient, making personalized
      and predictive medicine a reality.

PMID- 19747114
TI  - Sexual dimorphism in autoimmune disease.
AB  - We briefly survey the concept of autoimmunity and nominate the range of
      autoimmune diseases that include multisystemic and organ-specific disorders, and
      cite prevalences of autoimmune diseases in males and females, in humans and in
      experimental animals. Most human autoimmune diseases such as systemic lupus
      erythematosus (SLE), multiple sclerosis (MS) and autoimmune thyroid disease, have
      an increased incidence and prevalence in females, but a few others such as
      autoimmune diabetes, the Guillain Barre syndrome (GBS) and psoriasis are
      increased in males. Animal models of autoimmunity show an equivalent sexual
      dimorphism. The possible reasons for the differing incidence and prevalence of
      autoimmune diseases in females and males engage our attention. Environmental
      exposures may differ for females and males. There are innate differences in the
      function of the female and male immune systems, and there is some evidence for
      differences between females and males in the ability of a target organ for
      autoimmunity to withstand damage. In seeking reasons for these differences, we
      review the role of sex hormones in immunity and include results of trials of
      hormone therapy in autoimmune diseases. The association of autoimmunity and
      pregnancy, a female-specific condition, is discussed, and the claimed effects of
      lymphoid cell microchimerism on provocation of autoimmunity are reviewed. Genetic
      predisposition is an important factor in autoimmune disease and we particularly
      focus on genes on the X and Y chromosomes, the role of X chromosome inactivation,
      and the interaction of the sex of the patient with other genetic factors. The
      possible role of epigenetic mechanisms, including environmental influences, is
      then surveyed. We assert that sex is a vital variable that must be considered in
      all immunological studies, as it should be at all levels of biological research.

PMID- 19747115
TI  - Ribosome inactivating proteins (RIPs) from Momordica charantia for anti viral
      therapy.
AB  - This review describes the nature and applications of ribosome inactivating
      proteins (RIPs) from Momordica charantia (bitter melon). RIPs from the plant
      kingdom have received much attention in biomedical research because they target
      conserved host protein synthesis machinery and show specificity towards human and
      animal cell targets. Recent studies aimed at unravelling the enzymatic activities
      of the M charantia RIPs provide a structural basis for their activities. It has
      been reported that RIPs are member of the single chain ribosome inactivating
      protein (SCRIP) family which act irreversibly on ribosome by removing adenine
      residue from eukaryotic ribosomal RNA. Various activities of RIPs include anti
      tumor, broad anti-viral, ribonuclease and deoxyribonuclease. MAP30 (Momordica
      Anti-HIV Protein), alpha- and beta-momorcharins inhibit HIV replication in
      acutely and chronically infected cells and thus are considered potential
      therapeutic agent in HIV infection and AIDS. Further, MAP30 improved the efficacy
      of anti-HIV therapy when used in combination with other anti-viral drugs. MAP30
      holds therapeutic promise over other RIPs because not only it is active against
      infection and replication of both HSV and HIV but is non toxic to normal cells.
      Here we review the nature, action, structure function relationship and
      applications of RIPs from Momordica charantia and evaluate their potential for
      anti-cancer and anti-viral therapy.

PMID- 19747116
TI  - Diagnostic approach to mitochondrial disorders: the need for a reliable
      biomarker.
AB  - Mitochondrial diseases (MD) are disorders caused by impairment of the
      mitochondrial electron transport chain (ETC). Phenotypes are polymorphous and may
      range from pure myopathy to multisystemic disorders. The genetic defect can be
      located on mitochondrial or nuclear DNA. The ETC is needed for oxidative
      phosphorylation (which provides the cell with the most efficient energetic
      outcome in terms of ATP production), and consists of five multimeric protein
      complexes located in the inner mitochondrial membrane. The ETC also requires
      cytochrome c and a small electron carrier, coenzyme Q10. One of the pathogenic
      mechanisms of ETC disorders is excessive accumulation of reactive oxygen species
      (ROS). Mitochondrial dysfunction and oxidative stress appear to have a strong
      impact also on the pathogenesis of neurodegenerative diseases. At present,
      diagnosis of MD requires a complex approach: measurement of serum lactate,
      exercise testing, electromyography, magnetic resonance spectroscopy, muscle
      histology and enzymology, and genetic analysis. Biomarkers are molecules
      associated with biological processes or regulatory mechanisms. A reliable
      biomarker for the screening or diagnosis of MD is still needed. In this paper we
      review the diagnostic approach to MD, from serum lactate to other blood and
      urinary markers, from muscular biopsy to imaging studies, and we highlight some
      potentially interesting perspectives in this field.

PMID- 19747118
TI  - Stem cell and gene therapeutic strategies for the treatment of multiple
      sclerosis.
AB  - Multiple sclerosis is a disease of the central nervous system that predmoninantly
      affects young adults. The pathogenic mechanisms are complex, however numerous
      studies indicate that the disease is initiated by an autoimmune attack on protein
      targets present in the central nervous system. Given that a dysfunctional immune
      system perpetuates the pathophysiological mechanisms that characterize this
      inflammatory disorder, several therapeutic approaches that target immune cells or
      their secreted mediators have been generated and are currently used clinically.
      Although these strategies have been partially beneficial to a proportion of
      patients, current therapies are not particularly effective at preventing disease
      progression. As such there is a large and unmet need for the development of more
      effective treatments. Owing to a number of promising results obtained in mouse
      models of multiple sclerosis, cell therapies implementing hematopoietic,
      mesenchymal and neural stem cells may provide practical vehicles for in situ
      immunomodulation, neuroprotection and regeneration. In concert with these
      approaches, gene therapy strategies are being investigated to restore antigen
      specific tolerance or to deliver anti-inflammatory molecules. Furthermore
      targeted delivery of glial or neurotropic factors, which counteract the activity
      of inhibitory molecules within the neurodegenerative component of the lesion, is
      also being pursued. It is conceivable that these experimental approaches alone,
      or in combination with emerging and current treatments, may establish a rational
      protocol for the treatment of multiple sclerosis and potentially other autoimmune
      disorders.

PMID- 19747120
TI  - ADME optimization and toxicity assessment in early- and late-phase drug
      discovery.
AB  - Integrating physicochemical, drug metabolism, pharmacokinetics, ADME, and
      toxicity assays into drug discovery in order to reduce the attrition rates in
      clinical development is reviewed. The review is organized around three main
      decision points used in discovery including hit generation, lead optimization and
      final candidate selection stages. The preclinical strategies used at each
      decision point are discussed from a drug discovery perspective. Typically,
      preclinical data produced at these stages use lower throughput assays, smaller
      amounts of compounds and operate within a timeframe that is consistent with the
      iterative cycle of most drug discovery research projects. Understanding the false
      positive rates of these drug discovery preclinical assays is a must in reducing
      attrition rates in development.

PMID- 19747119
TI  - Quinolones: action and resistance updated.
AB  - The quinolones trap DNA gyrase and DNA topoisomerase IV on DNA as complexes in
      which the DNA is broken but constrained by protein. Early studies suggested that
      drug binding occurs largely along helix-4 of the GyrA (gyrase) and ParC
      (topoisomerase IV) proteins. However, recent X-ray crystallography shows drug
      intercalating between the -1 and +1 nucleotides of cut DNA, with only one end of
      the drug extending to helix-4. These two models may reflect distinct structural
      steps in complex formation. A consequence of drug-enzyme-DNA complex formation is
      reversible inhibition of DNA replication; cell death arises from subsequent
      events in which bacterial chromosomes are fragmented through two poorly
      understood pathways. In one pathway, chromosome fragmentation stimulates
      excessive accumulation of highly toxic reactive oxygen species that are
      responsible for cell death. Quinolone resistance arises stepwise through
      selective amplification of mutants when drug concentrations are above the MIC and
      below the MPC, as observed with static agar plate assays, dynamic in vitro
      systems, and experimental infection of rabbits. The gap between MIC and MPC can
      be narrowed by compound design that should restrict the emergence of resistance.
      Resistance is likely to become increasingly important, since three types of
      plasmid-borne resistance have been reported.

PMID- 19747121
TI  - The p38alpha kinase plays a central role in inflammation.
AB  - The p38 kinase plays a central role in inflammation, and it has been the subject
      of extensive efforts in both basic research and drug discovery. This review
      summarizes the biology of the p38 kinase with a focus on its role in
      inflammation. The p38 kinase regulates the production of key inflammatory
      mediators by cells of the innate immune system, including TNFalpha, IL-1beta, and
      COX-2. In addition, p38 also acts downstream of cytokines such as TNFalpha,
      mediating some of their effects. Recently p38 has also been found to play a role
      in responses of T cells, including Th17 and regulatory T cells. Consistent with
      its important role in inflammation, recent evidence suggests cells may utilize a
      variety of feedback mechanisms to regulate and maintain p38 signal transduction.
      The biological processes regulated by p38 kinase suggest both a wide variety of
      potential indications for inhibitors and a level of complexity that has proven
      challenging to drug discovery efforts around this target.

PMID- 19747123
TI  - Endogenous opioids and addiction to alcohol and other drugs of abuse.
AB  - There is significant experimental evidence implicating the endogenous opioid
      system (opioid peptides and opioid receptors) with the processes of reward and
      reinforcement. Indeed, many behaviors associated with reward and reinforcement,
      for example feeding behavior, are controlled by distinct components of the
      endogenous opioid system located in relevant brain regions. It has also been
      shown that regardless of their initial site of action many drugs of abuse, such
      as morphine, nicotine, cocaine, alcohol and amphetamines, induce an increase in
      the extracellular concentration of dopamine in the nucleus accumbens. This,
      increased secretion of dopamine in the nucleus accumbens seems to be a common
      effect of many drugs of abuse, and it was proposed that may mediate their
      rewarding and reinforcing properties. Furthermore, activation of mu opioid
      receptors in the ventral tegmental area, or of mu and delta opioid receptors in
      the nucleus accumbens enhances the extracellular concentration of dopamine in the
      nucleus accumbens. Thus, stimulation of the activity of distinct components of
      the endogenous opioid system either by opioid or by other drugs of abuse, may
      mediate some of their reinforcing effects. In this review article, a brief
      description of the endogenous opioid system and its implication in the processes
      of reward and reinforcement of opioid and other drugs of abuse will be presented.
      Furthermore, the use of opioid antagonists in the treatment of drug addiction
      will be discussed. Special emphasis will be given to ethanol addiction, the drug
      mainly studied in my laboratory.

PMID- 19747122
TI  - HIV-1 IN inhibitors: 2010 update and perspectives.
AB  - Integrase (IN) is the newest validated target against AIDS and retroviral
      infections. The remarkable activity of raltegravir (Isentress((R))) led to its
      rapid approval by the FDA in 2007 as the first IN inhibitor. Several other IN
      strand transfer inhibitors (STIs) are in development with the primary goal to
      overcome resistance due to the rapid occurrence of IN mutations in raltegravir
      treated patients. Thus, many scientists and drug companies are actively pursuing
      clinically useful IN inhibitors. The objective of this review is to provide an
      update on the IN inhibitors reported in the last two years, including second
      generation STI, recently developed hydroxylated aromatics, natural products,
      peptide, antibody and oligonucleotide inhibitors. Additionally, the targeting of
      IN cofactors such as LEDGF and Vpr will be discussed as novel strategies for the
      treatment of AIDS.

PMID- 19747124
TI  - QSAR modeling for quinoxaline derivatives using genetic algorithm and simulated
      annealing based feature selection.
AB  - With a view to the rational design of selective quinoxaline derivatives, 2D and
      3D-QSAR models have been developed for the prediction of anti-tubercular
      activities. Successful implementation of a predictive QSAR model largely depends
      on the selection of a preferred set of molecular descriptors that can signify the
      chemico-biological interaction. Genetic algorithm (GA) and simulated annealing
      (SA) are applied as variable selection methods for model development. 2D-QSAR
      modeling using GA or SA based partial least squares (GA-PLS and SA-PLS) methods
      identified some important topological and electrostatic descriptors as important
      factor for tubercular activity. Kohonen network and counter propagation
      artificial neural network (CP-ANN) considering GA and SA based feature selection
      methods have been applied for such QSAR modeling of Quinoxaline compounds. Out of
      a variable pool of 380 molecular descriptors, predictive QSAR models are
      developed for the training set and validated on the test set compounds and a
      comparative study of the relative effectiveness of linear and non-linear
      approaches has been investigated. Further analysis using 3D-QSAR technique
      identifies two models obtained by GA-PLS and SA-PLS methods leading to anti
      tubercular activity prediction. The influences of steric and electrostatic field
      effects generated by the contribution plots are discussed. The results indicate
      that SA is a very effective variable selection approach for such 3D-QSAR
      modeling.

PMID- 19747125
TI  - Natriuretic peptides in septic patients.
AB  - The natriuretic peptide family is comprised of atrial natriuretic peptide (ANP),
      brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP), dendroaspis
      natriuretic peptide - DNP and urodilatin. They play a role in the diagnosis of
      several diseases, especially those involving the cardiovascular system. Sepsis is
      a complex condition that can lead to multiorgan failure, shock and death. The
      number of people developing sepsis is still increasing (approximately 750,000
      cases of sepsis occur annually in the USA). Both ANP and pro-ANP have attracted
      interest as new markers for sepsis. Reports indicate that ANP or BNP levels are
      elevated in septic patients. However, many mechanisms are still unexplained. This
      situation is complicated by the fact that contradictory results have been
      published. There are several reasons for this controversy including differences
      in the techniques used to assay natriuretic peptides. Nevertheless, natriuretic
      peptides might eventually prove useful for the diagnosis and/or the treatment of
      septic patients.

PMID- 19747126
TI  - Staphylococcus aureus: the toxic presence of a pathogen extraordinaire.
AB  - Staphylococcus aureus is a facultative, Gram-positive coccus well known for its
      disease-causing capabilities. In particular, methicillin and vancomycin resistant
      strains of S. aureus (MRSA and VRSA, respectively) isolated globally represent
      daunting medical challenges for the 21(st) Century. This bacterium causes
      numerous illnesses in humans such as food poisoning, skin infections,
      osteomyelitis, endocarditis, pneumonia, enterocolitis, toxic shock, and
      autoimmune disorders. A few of the many virulence factors attributed to S. aureus
      include antibiotic resistance, capsule, coagulase, lipase, hyaluronidase, protein
      A, fibronectin-binding protein, and multiple toxins with diverse activities. One
      family of protein toxins is the staphylococcal enterotoxins (SEs) and related
      toxic shock syndrome toxin-1 (TSST-1) that act as superantigens. There are more
      than twenty different SEs described to date with varying amino acid sequences,
      common conformations, and similar biological effects. By definition, very low
      (picomolar) concentrations of these superantigenic toxins activate specific T
      cell subsets after binding to major histocompatibility complex class II.
      Activated T-cells vigorously proliferate and release proinflammatory cytokines
      plus chemokines that can elicit fever, hypotension, and other ailments which
      include a potentially lethal shock. In vitro and in vivo models are available for
      studying the SEs and TSST-1, thus providing important tools for understanding
      modes of action and subsequently countering these toxins via experimental
      vaccines or therapeutics. This review succinctly presents the pathogenic ways of
      S. aureus, with a toxic twist. There will be a particular focus upon the
      biological and biochemical properties of, plus current neutralization strategies
      targeting, staphylcoccocal superantigens like the SEs and TSST-1.

PMID- 19747127
TI  - The antibacterial effect of a proline-rich antibacterial peptide A3-APO.
AB  - Antimicrobial resistance is an emerging worldwide concern in light of the
      widespread antimicrobial drug use in humans, livestock and companion animals. The
      treatment of life-threatening infections is especially problematic because
      clinical strains rapidly acquire multiple-drug resistance. Antimicrobial peptides
      have long been considered to be viable alternatives to small molecule
      antibiotics. However, the peptides' parenteral use is frequently hampered by
      inadequate safety margins and rapid renal clearance leaving them suitable only
      for topical applications. The proline-rich peptide A3-APO represents a family of
      a new class of synthetic dimers that kill bacteria by a dual mode of action and
      carry domains for interaction with both the bacterial membrane and an
      intracellular target. From a series of designer antibacterial peptides, A3-APO
      emerged as a viable preclinical candidate by virtue of its superior ability to
      disintegrate the bacterial membrane, inhibit the 70-kDa heat shock protein DnaK
      alone or in synergy with small molecule antibiotics, lack of eukaryotic toxicity
      and withstand proteolytic degradation in body fluids. As many other proline-rich
      peptides, A3-APO binds to the C-terminal helical lid of bacterial DnaK and
      inhibits chaperone-assisted protein folding in bacteria but not in mammalian
      Hsp70. In this review, the structure, pharmacokinetic properties, antimicrobial
      spectrum of peptide A3-APO and its in vivo metabolite are summarized and the in
      vitro and in vivo antimicrobial effects (antimicrobial susceptibilities,
      postantibiotic effects, resistance induction) are discussed in detail.

PMID- 19747128
TI  - Systemic sclerosis at the cellular level: molecular pathways of pathogenesis and
      its implication on future drug design.
AB  - Endothelial cell abnormalities and the effects on the surrounding
      microvasculature is a focal point in the pathogenesis of Systemic Sclerosis
      disease and may even be the sentinel event for the initiation of this disorder. A
      better understanding of these processes may improve our understanding of the
      pathophysiology of Systemic Sclerosis and more specifically the vasculopathy
      observed. Such knowledge will help us to further current treatments options and
      design novel therapies for Systemic Sclerosis and other fibrotic disorders.

PMID- 19747129
TI  - Medicinal chemistry of paclitaxel and its analogues.
AB  - Paclitaxel belongs to the most successful anticancer drugs developed and utilised
      during the past two decades. Nevertheless, the development of resistance of tumor
      cells and severe side effects in the patients require further improvement of the
      drug. In this review, we provide a detailed overview of the state-of-the-art in
      the medicinal chemistry of paclitaxel and its analogues. A number of strategies
      have been explored to obtain sufficient amounts of paclitaxel for clinical use
      from natural resources. Semi-synthesis from its precursor, 10-deacetylbaccatin
      III, which can be extracted from Taxus leavesturned out as the most appropriate
      method for commercial production. So far, many paclitaxel derivatives have been
      synthesized, and their effect on microtubules stabilization and cytotoxicity were
      investigated in terms of structure-activity relationships (SAR). One of them,
      docetaxel, was approved as a more potent anticancer agent than paclitaxel towards
      a variety of tumor types. This review summarizes current possibilities to harvest
      sufficient amount of drugs from natural sources, including the production of
      taxanes in bioreactors and synthetic approaches for paclitaxel and its analogues,
      their mechanism of action and structure-activity relationships. In addition,
      future developments and perspectives for this class of compounds are outlined.

PMID- 19747130
TI  - Plant polyphenols and tumors: from mechanisms to therapies, prevention, and
      protection against toxicity of anti-cancer treatments.
AB  - Polyphenolic molecules produced by higher plants in response to biotic and
      abiotic stresses exert numerous effects on tumorigenic cell transformation, and
      on tumor cells in vitro and in vivo, and may interact with conventional anti
      tumor therapies. In the present review, we collected and critically discussed
      data on: (i) redox-dependent and redox-independent mechanisms underlying
      cytotoxic/cytostatic effects of PPs and their metabolites towards tumor cells and
      cytoprotection of normal cells; (ii) mechanisms of anti-angiogenic and anti
      metastatic action of PPs; (iii) PPs-associated phototoxicity against tumor cells
      and photoprotection of non-tumor cells; (iv) PPs effects on drug-metabolizing
      enzymes as a basis for their synergism or antagonism with chemotherapy; (v)
      molecular pathways leading to tumor chemoprevention by PPs; and (vi) PPs as
      protectors against toxic effects of chemo-, radio-, and photodynamic therapies.

PMID- 19747131
TI  - The effects of insulin and insulin-like growth factors on tumor vascularization:
      new insights of insulin-like growth factor family in cancer.
AB  - It is currently believed that the development of a clinically relevant tumor
      needs new vessel formation provided by both angiogenesis (primary involving
      endothelial cells) and postnatal vasculogenesis (primary involving bone marrow
      derived cells). Clearly, it is important to identify factors that help to enhance
      the growth and "health" of tumors, as well as their further vascularization. The
      Insulin and Insulin-like Growth Factors (IGFs) systems play a key role in
      cellular metabolism, differentiation, proliferation, transformation and
      apoptosis, during normal and malignant growth. Moreover, these molecules seem
      essential in promoting tumor vascularization. Due to the complexity of these
      systems, the review has been focused on the role of insulin and IGFs signaling in
      the regulation of tumor angiogenesis and postnatal vasculogenesis. Since
      targeting on IGF for cancer therapy is rapidly becoming a clinical reality, a
      better understanding of IGFs-mediated pathways has a relevant impact, providing
      new insights to help the design of newly developed drugs.

PMID- 19747132
TI  - Angiogenesis inhibitors and vascular disrupting agents in non-small cell lung
      cancer.
AB  - Most patients diagnosed with non-small cell lung cancer (NSCLC) have advanced
      disease. Chemotherapy has apparently reached a plateau of effectiveness in
      improving survival in this subgroup of patients. Considerable efforts have been
      initiated to identify novel targets for new biological agents which may be safely
      and effectively administered to NSCLC patients. New blood vessel formation, known
      as angiogenesis, is a fundamental event in the process of tumor growth and
      metastatic dissemination. The vascular endothelial growth factor (VEGF) and its
      receptors play an essential role in tumor proliferation. Approaches to limit VEGF
      activity include monoclonal antibodies (mAbs) and small molecules inhibiting the
      corresponding receptor-tyrosine kinase activity. Bevacizumab, an anti-VEGF
      recombinant humanized mAb, is the first targeted agent which, when combined with
      chemotherapy, has shown superior efficacy versus chemotherapy alone as first-line
      treatment of advanced NSCLC. Future clinical developments of bevacizumab in NSCLC
      treatment include the combination with other targeted therapies in advanced
      disease, and the integration into the combined modality approaches for the
      treatment of early and locally advanced disease stages. Vandetanib, a small
      molecule targeting VEGF tyrosine-kinase activity, due to first indications of
      antitumor activity and the excellent toxicity profile seems to be a promising
      agent for the treatment of advanced NSCLC. Other antiangiogenic drugs, such as
      sorafenib, sunitinib, VEGF Trap and a new class named 'vascular disrupting
      agents', which includes ASA404, are being tested in ongoing clinical trials which
      will further define their role in the management of NSCLC. This paper reviews the
      state of the art and the future developments of the main antiangiogenic agents in
      the treatment of NSCLC patients.

PMID- 19747133
TI  - Design strategies of novel NNRTIs to overcome drug resistance.
AB  - Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are very potent and most
      promising anti-AIDS drugs that specifically inhibit HIV-1 reverse transcriptase
      (RT). However, to a great extent, the efficacy of NNRTI drugs is impaired by
      rapid emergence of drug-resistance mutations. Fortunately, detailed analysis of a
      wide range of crystal structures of HIV-1 RT/NNRTI complexes together with data
      on drug resistance mutations has identified factors important for design of
      inhibitors and resilience to mutations, such as, exhibiting conformational
      flexibility and positional adaptability of NNRTIs, forming extensive main chain
      hydrogen bonding, targeting highly conserved residues in HIV-1 RT and possessing
      unconventional mechanisms for NNRTI-mediated inhibition of RT. Besides, the
      plasticity of NNRTIs binding pocket (NNIBP) also provides a broad space for the
      discovery of new generations of NNRTIs. For instance, the composite binding
      pocket, integrated all available crystal structure information about the NNRTI
      binding site of HIV RT, was demonstrated to be an effective tool to better
      understand the flexible nature of the binding pocket and to identify specific
      inhibitors. The RT/solvent interface proved to be an attractive site for
      incorporating a moiety to improve water solubility and pharmacokinetics or
      introducing a second pharmacophore to construct multifunctional ligand. Totally,
      the characterization of NNRTIs and NNIBP may help in the design of more effective
      drugs that are potent toward wild type and drug-resistant strains of RT. In this
      paper we attempt to translate the general knowledge gained from a large number of
      related literature into a set of medicinal chemistry strategies to improve the
      drug resistance profile of NNRTIs.

PMID- 19747134
TI  - Role of nuclear steroid receptors in apoptosis.
AB  - Nuclear steroid receptors (NSR) are ligand-activated transcription factors that
      play a key role in a variety of vital physiological phenomena including
      developmental or endocrine signaling, reproduction, and homeostasis. In addition,
      they are implicated in other important biological processes, such as apoptosis.
      Modulation of apoptosis by NSR is mostly associated with control of pro-apoptotic
      versus anti-apoptotic gene expression, and includes both induction and prevention
      of apoptosis depending on cell type. However, it is unclear how NSR can affect
      opposing expression of the same gene in different cells. Of note, recently
      described nongenomic mechanisms of NSR, in particular glucocorticoid receptor
      translocation to mitochondria, were suggested to be crucial steps for triggering
      apoptosis. NSR often act solely as nuclear transporters of other regulatory
      molecules, thus indirectly regulating several apoptosis-related genes. Curiously,
      NSR are thought to cooperate with the anti-apoptotic endogenous bile acid,
      ursodeoxycholic acid (UDCA), to prevent programmed cell death. In fact, as
      cholesterol-derived molecules and due to their chemical and structural
      similarities to steroid hormones, bile acids also modulate NSR activation.
      Although the precise link between NSR and UDCA remains unclear, we have
      demonstrated that the bile acid requires NSR for translocation to the cell
      nucleus as part of a ligand-receptor complex, using a mechanism similar to that
      of steroid hormones. Interestingly, other studies revealed that UDCA interacts
      with the glucocorticoid receptor as a novel and selective NSR modifier. The huge
      diversity of natural ligands and xenobiotics that bind to NSR and regulate their
      function represents one of the most exciting drug targets for potential
      therapeutic intervention. The next decade will almost certainly unveil the
      remarkable role of NSR in modulating cell fate in human health and disease.

PMID- 19747135
TI  - Adenosine and adenosine receptors: their contribution to airway inflammation and
      therapeutic potential in asthma.
AB  - Growing evidence emphasizes that the purine nucleoside adenosine plays an active
      role as local regulator in airway inflammation and pulmonary diseases. The notion
      that increased adenosine concentrations are associated with lung inflammation
      indicates the importance of this signaling pathway, which involves the activation
      of a family of cell surface G-protein coupled receptor subtypes named as A(1),
      A(2A), A(2B) and A(3). Recently, important progress has been made to better
      clarify the role of these receptors in a variety of inflammatory airway disorders
      including asthma. As a consequence, new molecules with high affinity and high
      selectivity for the human adenosine receptors subtypes designed to control the
      airway inflammatory component of asthma have been launched and are currently
      tested in clinical trials as anti-asthma treatments. With the availability of
      these molecules for testing in humans, the role of adenosine receptors in asthma
      can now be validated.

PMID- 19747136
TI  - Medicinal chemistry approaches for glucokinase activation to treat type 2
      diabetes.
AB  - Type 2 Diabetes (T2D), characterized by elevated levels of blood glucose is a
      complex disease mainly caused by defects in hepatic glucose balance and the
      failure of pancreatic beta-cells to secrete enough insulin to overcome insulin
      resistance. Glucokinase (GK) is a member of hexokinase family of enzymes that are
      responsible for the phosphorylation of glucose to glucose-6-phosphate for further
      utilization in cells. It plays a key role in glucose homeostasis in cells that
      express this enzyme, such as beta-cells and hepatocytes. It promotes glycogen
      synthesis in the liver and glucose-sensitive insulin release in the beta-cell.
      While hypoglycemia due to the increased insulin secretion could be a potential
      concern it was hypothesized that a GK activator with optimized properties would
      be able to both blunt the postprandial glucose excursion and lower the fasting
      blood glucose in T2D patients. As a result of intensive medicinal chemistry
      efforts a number of small molecules have been discovered as GK activators many of
      which showed antidiabetic effects in animal models of T2D. Some of these
      activators have advanced into human clinical studies. With the promising
      preclinical data in hand, GK activators represent a promising and new treatment
      option for T2D.

PMID- 19747138
TI  - Circulating biomarkers for the diagnosis and prognosis of heart failure.
AB  - Despite substantial therapeutic advances, heart failure remains a syndrome
      associated with high morbidity and mortality. The management of heart failure
      remains challenging despite the recent different therapeutic advances. The
      emergence of cardiac biomarkers as increasingly effective clinical tools suggests
      the potential of a new approach to the management of patients with heart failure.
      A variety of circulating biomarkers of diagnostic and prognostic utility in heart
      failure is currently being studies in preclinical, observational and randomized
      prospective studies. Of the various candidate biomarkers, the greatest wealth of
      knowledge and clinical experience lies with the B-type naturetic peptides.
      However, because individual biomarkers may have limited sensitivity and
      specificity, a multi-marker approach, using combinations of different biomarkers
      that reflect different aspects of the pathophysiological milieu, would contribute
      to better risk stratification and optimization of therapy.

PMID- 19747139
TI  - Selective matrix metalloproteinase inhibitors for cancer.
AB  - The matrix metalloproteinases are a family of nearly 30 enzymes that are
      intimately involved in tissue remodeling. Disease processes associated with the
      matrix metalloproteinases are generally related to imbalance between the
      inhibition and activation of matrix metalloproteinases resulting in excessive
      degradation of the extracellullar matrix. These include osteoarthritis,
      rheumatoid arthritis, tumor metastasis and congestive heart failure. Despite
      massive research and development efforts, there are only two drugs launched on
      the market: periostat (doxycycline), a tetracycline used for periodontal disease
      and glucosemine sulfate, for osteoarthritis. Possible reasons for the low success
      rate of matrix metalloproteinase inhibitors in the clinic are mainly from
      unwanted side effects caused by their lack of selectivity, since inhibition of
      collagenase-1 may be responsible for the musculoskeletal side effects observed
      clinically with broad-spectrum inhibitors. Considering these data, many efforts
      were directed to developing a more selective second generation of inhibitors
      against the specific matrix metalloproteinases believed to be involved in the
      different pathologies. This review mainly focuses on selective matrix
      metalloproteinase inhibitors development on matrix metalloproteinases in terms of
      antitumor since the late 90s, in terms of synthetic compounds of low molecular
      mass incorporating specific zinc-binding groups, natural products and their
      derivatives. Through these methods, new hope is emerging in the form of synthetic
      and natural matrix metalloproteinase inhibitors for the prevention and treatment
      of cancer.

PMID- 19747137
TI  - Cardiovascular effects of losartan and its relevant clinical application.
AB  - The renin-angiotensin system (RAS) plays an important role in the homeostasis of
      the cardiovascular system and in the development of cardiovascular diseases. An
      abnormal expression or over activation of the local RAS in the heart and
      vasculature system is one of the most common mechanisms in pathophysiological
      processes in cardiovascular diseases. This also provides a basis for medical
      prevention and treatments using chemical approaches. Losartan is a selective
      nonpeptite antagonist against type 1 angiotensin II receptors (AT1R), and has
      been applied in medical treatments of a variety of cardiovascular diseases,
      including essential hypertension. This article reviews direct and indirect
      cardiovascular effects of losartan on the heart and blood vessels. It summarizes
      the chemical basis of AT1R for the action site of losartan,focuses on the
      mechanisms underlying the action of losartan involved in both the heart and
      vasculature, and reviews the information that may be helpful in the development
      of new chemical candidates or approaches in the war against cardiovascular
      diseases.

PMID- 19747140
TI  - Targeting epidermal growth factor receptor in solid tumors: critical evaluation
      of the biological importance of therapeutic monoclonal antibodies.
AB  - Numerous cellular pathways have a significant impact in the growth and metastatic
      potential of tumors. Essential element of such pathways is the epidermal growth
      factor receptor (EGFR), a member of the HER family of receptor tyrosine kinases.
      One of the most important issues in cancer, which attracted the attention of
      clinical oncologists, is the potential use of targeted therapies. EGFR signaling
      pathway is implicated in the control of cell survival, proliferation, metastasis
      and angiogenesis. EGFR is, therefore, an appealing target for molecular-targeted
      cancer therapy as it is expressed in a variety of solid tumors (colorectal,
      breast, head and neck, etc.). Receptor antagonists that target EGFR have already
      been of high interest for a number of years. Multiple therapeutic strategies have
      been developed to target EGFR, including monoclonal antibodies (mAbs), tyrosine
      kinase inhibitors (TKIs), ligand-toxin conjugates, and antisense
      oligonucleotides. In particular, mAbs block ligand from binding to the
      extracellular domain of the receptor. Two mAbs that block EGFR (erbB1), cetuximab
      and panitumumab, have been approved by FDA. Cetuximab is a chimeric IgG1 anti
      EGFR monoclonal antibody, whereas panitumumab is a fully human IgG2 anti-EGFR
      monoclonal antibody. This review highlights the cellular effects of EGFR blockade
      by mAbs and their relationship to therapeutic efficacy and biological
      significance.

PMID- 19747141
TI  - Caged Garcinia xanthones: development since 1937.
AB  - Caged xanthones, characterized by a unique 4-oxa-tricyclo[4.3.1.0(3,7)]dec-2-one
      scaffold, are a special class of bioactive components mainly derived from the
      Garcinia genus (Guttiferae family). Around 100 compounds from this family have
      been reported to date and most of them have potent antitumor activity, with
      gambogic acid being the best representative. During the past decades, inspired by
      the unusual caged skeleton and remarkable bioactivity, scientists from various
      fields have shown increasing interest on these promising natural products. In
      this review, the plant resources, structural characteristics, total synthesis,
      biological activity and mechanisms of action, structure activity relationship,
      and anticancer drug development of these caged xanthones are described.

PMID- 19747142
TI  - Functional variants of the interleukin-23 receptor gene in non-gastrointestinal
      autoimmune diseases.
AB  - Variants of the gene of the interleukin-23 receptor (IL23R) were first identified
      as susceptibility factors in association with inflammatory bowel diseases. Since
      then it became clear that different variants of the gene play also role in a
      number of other autoimmune diseases like psoriasis, rheumatoid arthritis,
      ankylosing spondylitis and multiple sclerosis while in others, like systemic
      sclerosis, systemic lupus erythematosus or Sjogren syndrome the same effect could
      not be seen. However, the results are very controversial both in terms of the
      various polymorphisms and also in population specificity. The aim of the current
      paper is to overview all available reports on IL23R gene polymorphisms in various
      autoimmune and inflammatory diseases and to try to give an explanation on the
      possible effect of the examined variants.

PMID- 19747143
TI  - Beta-lactamase inhibitors: the story so far.
AB  - Antimicrobial resistance constitutes one of the major threats regarding
      pathogenic microorganisms. Gram-negative pathogens, such as Enterobacteriaceae
      (specially those producing extended-spectrum beta-lactamases), Pseudomonas
      aeruginosa, and Acinetobacter baumannii have acquired an important role in
      hospital infections, which is of particular concern because of the associated
      broad spectrum of antibiotic resistance. beta-Lactam antibiotics are considered
      the most successful antimicrobial agents since the beginning of the antibiotic
      era. Soon after the introduction of penicillin, microorganisms able to destroy
      this beta-lactam antibiotic were reported, thus emphasizing the facility of
      pathogenic microorganisms to develop beta-lactam resistance. In Gram-negative
      pathogens, beta-lactamase production is the main mechanism involved in acquired
      beta-lactam resistance. Four classes of beta-lactamases have been described: A,
      B, C, and D. Classes A, C, and D are enzymes with a serine moiety in the active
      centre that catalyzes hydrolysis of the beta -lactam ring through an acyl
      intermediate of serine, whereas the class B enzymes require a metal cofactor
      (e.g. zinc in the natural form) to function, and for this reason, they are also
      referred to as metallo- beta-lactamases (MBLs). To overcome beta-lactamase
      mediated resistance, a combination of beta-lactam and a beta-lactamase inhibitor,
      which protects the beta-lactam antibiotic from the activity of the beta
      lactamase, has been widely used in the treatment of human infections. Although
      there are some very successful combinations of beta-lactams and beta-lactamase
      inhibitors, most of the inhibitors act against class A beta-lactamases and remain
      ineffective against class B, C, and D beta-lactamases. This review constitutes an
      update of the current status and knowledge regarding class A to D beta-lactamase
      inhibitors, as well as a summary of the drug discovery strategy currently used to
      identify new beta-lactamase inhibitors, mainly based on the knowledge of crystal
      structure of beta-lactamase enzymes.

PMID- 19747144
TI  - Potential targets and their relevant inhibitors in anti-influenza fields.
AB  - Influenza is a disease for deeply affecting millions of people every year.
      Recently, there has been considerable concern regarding the highly pathogenic
      H5N1 avian influenza virus, and its human pandemic potential. With developments
      in viral biology, there are more novel antiviral strategies targeting these
      viruses. In this review, we will discuss several proven and potential anti
      influenza targets, including viral factors (such as hemagglutinin (HA), M2 ion
      channel protein, RNA-dependent RNA polymerase (RdRp), nucleoprotein (NP), non
      structural protein (NS) and neuraminidase (NA)) and host factors (such as v
      ATPase, protease, inosine monophosphate dehydrogenase (IMPDH) and intracellular
      signalling cascades), and their relevant inhibitors.

PMID- 19747146
TI  - Methionine-derived metabolites in apoptosis: therapeutic opportunities for
      inhibitors of their metabolism in chemoresistant cancer cells.
AB  - Methionine, in addition to its role in protein synthesis, participates in 3
      important cellular functions: as AdoMet in transmethylation; as decarboxylated
      AdoMet in aminopropylation; as homocysteine its demethylated form, in trans
      sulphuration. Here we provide evidence from the literature and from our own work
      for a fourth role for its oxoacid: 4-methylthio-2-oxo-butanoate (MTOB) in
      apoptosis [28,29]. MTOB enters 2 pathways: (a) transamination by glutamine
      transaminase K to methionine[13,14].(b)oxidative decarboxylation by the
      mitochondrial Branched-Chain-Oxo-Acid-Dehydrogenase-Complex to methional and
      finally to methylthiopropanoyl CoA (MTPCoA) [26,27]. Some of the methional formed
      after MTOB decarboxylation leaks into the cytoplasm as free methional [29].
      Exogenous methional induces apoptosis in normal and cancer cells in culture [28,
      29] but not in those overexpressing the antiapoptotic gene bcl2 [30]. In
      physiologically-induced apoptosis e.g; trophic factor (IL3) withdrawal, methional
      leakage is decreased [29] suggesting that MTPCoA is also involved in apoptosis.
      Both methional and MTPCoA give rise to metabolites that may act as cross-linking
      agents. In the case of methional, the CH3-S moiety is lost and malondialdehyde
      (MDA) is formed when methional is subjected to ( )OH attack [29]. MDA generated
      in situ from 1,3-propanediol, induces DNA-protein cross-linking [41].With regard
      to MTPCoA, it is metabolized to malonic semialdehyde CoA (MASACoA) with loss of
      the CH3-S moiety [48,49]. The capacity of MASACoA to form cross-links has not yet
      been established experimentally, but it could be a substrate for one of the
      histone acyl transferases [50, 51] and so form amides via the CoA at one end and
      imines by its CHO group at the other, with amino groups on proteins. Chromatin
      cross-linking/condensation is one of the hall-marks of apoptosis [40]. Methional,
      MDA and other apoptogenic aldehydes like 4-hydroxy-2-nonenal are oxidized by
      ALDHs to non-apoptogenic carboxylic acids [29,44, 45,68] but retain their
      apoptotic activity when the ALDHs are inhibited [98,110]. MASACoA would also lose
      its cross-linking capacity if its CoA moiety were putatively hydrolysed by ALDHs
      and/or acylCoA thioesterases [56,58,88,89]. ALDH inhibitors that control cellular
      MDA and possibly MASACoA homeostasis are cited as examples of targeted
      therapeutic approaches in chemoresistant cancers [62,84,97,98,110].

PMID- 19747147
TI  - The role of cellular plasticity in cancer development.
AB  - It has traditionally been accepted that, in the process of cellular
      differentiation, developmental options are progressively restricted until
      commitment to a specific fate is established and then only terminal
      differentiation along this lineage is possible. Although this is usually the case
      in normal physiological development, the latest experimental evidences indicate
      that the differentiated state of mature cells is not always as stable and durable
      as it was thought to be. In fact, recently, a hidden plasticity has been revealed
      in differentiated cells which allows them to deviate to other cell types that
      might be, functionally, very far away in other developmental pathways. This
      plasticity has biological significance since it is necessary for normal
      development to occur, but it also makes possible the emergence of aberrant
      lineages when interferences with the normal transcriptional and epigenetic
      mechanisms in charge of maintaining cellular identity do appear. Cancer is one of
      the possible outcomes of this aberrant reprogramming. The plasticity of the
      initial cell suffering the first oncogenic alteration plays an essential role in
      cancer development, since only if this cell possesses enough plasticity a tumoral
      reprogramming will be possible and a full-blown tumor will develop. Also,
      plasticity makes it possible for differentiated cells to acquire cancer stem cell
      properties in the presence of the appropriate oncogenic insults. In this review
      we discuss the role of cellular plasticity in the normal development of adult
      tissues and how cellular susceptibility to reprogramming plays an essential part
      in cancer development.

PMID- 19747148
TI  - Agaves as a raw material: recent technologies and applications.
AB  - Agave plants are a valuable source of raw material due to its fibrous and complex
      sugar content of their leaves and core, and their bagasse waste can be use for
      several aims. This plant genus belongs to the Agavaceae family and until now more
      than 200 species have been described. A large number of Agave species are
      currently used as raw material in several biotechnological processes. This review
      shows the reported applications and patents on fields like alcoholic brewages
      with special reference to Tequila and Mezcal, the isolation and use of compounds
      such as saponins and agave fructans, and their potential biotechnological
      application on several human demands. The process to obtain fibers and cellulose,
      stock feeds, and several miscellaneous extractives are also reviewed. Some
      possibilities and problems of cultivation are discussed.

PMID- 19747145
TI  - Losartan chemistry and its effects via AT1 mechanisms in the kidney.
AB  - Besides the importance of the renin-angiotensin system (RAS) in the circulation
      and other organs, the local RAS in the kidney has attracted a great attention in
      research in last decades. The renal RAS plays an important role in the body fluid
      homeostasis and long-term cardiovascular regulation. All major components and key
      enzymes for the establishment of a local RAS as well as two important angiotensin
      II (Ang II) receptor subtypes, AT1 and AT2 receptors, have been confirmed in the
      kidney. In additional to renal contribution to the systemic RAS, the intrarenal
      RAS plays a critical role in the regulation of renal function as well as in the
      development of kidney disease. Notably, kidney AT1 receptors locating at
      different cells and compartments inside the kidney are important for normal renal
      physiological functions and abnormal pathophysiological processes. This mini
      review focuses on: 1) the local renal RAS and its receptors, particularly the AT1
      receptor and its mechanisms in physiological and pathophysiological processes;
      and 2) the chemistry of the selective AT1 receptor blocker, losartan, and the
      potential mechanisms for its actions in the renal RAS-mediated disease.

PMID- 19747149
TI  - Strain improvement and process development for biobutanol production.
AB  - Among various renewable and sustainable energy sources being explored, biobutanol
      has been recognized as one of the promising alternatives for biofuels due to its
      attractive physical and chemical properties. Various inventions have been
      reported for the biological production of butanol, maintaining its
      competitiveness in efficiency, economy, and production scale. This article
      reviews such patented inventions and relevant research achievements to the
      microbial strains and fermentation processes for the enhanced production of
      biobutanol. We also discuss current challenges for strain improvement based on
      recent developments.

PMID- 19747150
TI  - Glutathione transferases: emerging multidisciplinary tools in red and green
      biotechnology.
AB  - Cytosolic glutathione transferases (GSTs) are a diverse family of enzymes
      involved in a wide range of biological processes, many of which involve the
      conjugation of the tripeptide glutathione (GSH) to an electrophilic substrate.
      Detailed studies of GSTs are justified because of the considerable interest of
      these enzymes in medicine, agriculture and analytical biotechnology. For example,
      in medicine, GSTs are explored as molecular targets for the design of new
      anticancer drugs as a plausible means to sensitize drug-resistant tumors that
      overexpress GSTs. In agriculture, GSTs are exploited in the development of
      transgenic plants with increased resistance to biotic and abiotic stresses.
      Recently, selected isoenzymes of GSTs have found successful applications in the
      development of enzyme biosensors for the direct monitoring of environmental
      pollutants, such as herbicides and insecticides. This review article summarizes
      recent representative patents related to GSTs and their applications in
      biotechnology.

PMID- 19747151
TI  - Recent patents on the Pichia pastoris expression system: expanding the toolbox
      for recombinant protein production.
AB  - Pichia pastoris is a widely used host system for heterologous protein expression
      both for basic research and industrial production purposes. Recent developments
      expanding the P. pastoris protein expression toolbox reflect the increasing
      interest in the application of yeast expression systems for protein-based
      pharmaceutical products, as an alternative to Escherichia coli and mammalian cell
      factories. The commonly used expression system for P. pastoris and the recent
      patents relevant to the P. pastoris genetic toolbox for recombinant protein
      production are reviewed.

PMID- 19747152
TI  - Synthetic strategies to a backbone-side chain cyclic SHP-1 N-SH2 ligand
      containing N-functionalized alkyl phosphotyrosine.
AB  - The cyclic peptide EGLNc Psi [CON((CH(2))(3)NH)pYNleE(NHCH(2)CO)]L-NH(2) (1) was
      designed and synthesized according to a native interaction partner of tyrosine
      phosphatase SHP-1. We introduced N-aminopropyl-phosphotyrosine to enable backbone
      side chain cyclization with a glutamic acid derivative as counterpart for
      cyclization. Different approaches have been compared to find a strategy for the
      generation of backbone and backbone-side chain cyclic phosphopeptides.

PMID- 19747153
TI  - Adult neurogenesis, neural stem cells and Alzheimer's disease: developments,
      limitations, problems and promises.
AB  - Alzheimer's disease (AD) is an irreversible progressive neurodegenerative
      disease, leading to severe incapacity and death. It is the most common form of
      dementia among older people. AD is characterized in the brain by amyloid plaques,
      neurofibrillary tangles, neuronal degeneration, aneuploidy and enhanced
      neurogenesis and by cognitive, behavioral and physical impairments. Inherited
      mutations in several genes and genetic, acquired and environmental risk factors
      have been reported as causes for developing the disease, for which there is
      currently no cure. Current treatments for AD involve drugs and occupational
      therapies, and future developments involve early diagnosis and stem cell therapy.
      In this manuscript, we will review and discuss the recent developments,
      limitations, problems and promises on AD, particularly related to aneuploidy,
      adult neurogenesis, neural stem cells (NSCs) and cellular therapy. Though adult
      neurogenesis may be beneficial for regeneration of the nervous system, it may
      underly the pathogenesis of AD. Cellular therapy is a promising strategy for AD.
      Limitations in protocols to establish homogeneous populations of neural
      progenitor and stem cells and niches for neurogenesis need to be resolved and
      unlocked, for the full potential of adult NSCs to be realized for therapy.

PMID- 19747154
TI  - Impact of Alzheimer's disease on the functional connectivity of spontaneous brain
      activity.
AB  - Alzheimer's disease (AD) prominently affects the structure and function of
      cerebral networks. Reflecting the complex network structure of the brain,
      spontaneous brain activity is organized by synchronized activity across distinct
      temporal and spatial scales. Temporal correlations of the functional MRI (fMRI)
      signal during rest have been used to characterize the impact of AD on the
      functional connectivity of spontaneous brain activity. Here we review studies
      using resting-state fMRI (rs-fMRI) to explore AD-induced changes of synchronized
      intrinsic activity at three levels of brain organization: the regional, inter
      regional and large-scale level. Changes in posterior areas of the default network
      (DN) and the medial temporal lobes seem to be central to AD. These areas show
      remarkable disturbances in neuronal communication at all spatial levels and in
      very early stages of the disease. Finally, rs-fMRI seems to have the potential to
      produce connectivity-related biomarkers that distinguish AD and healthy aging.

PMID- 19747155
TI  - Prospects for early detection of Alzheimer's disease from serial MR images in
      transgenic mice.
AB  - The existing literature on the magnetic resonance imaging of murine models of
      Alzheimer's disease is reviewed. Particular attention is paid to the
      possibilities for the early detection of the disease. To this effect, not only
      are relaxometric and volumetric approaches discussed, but also mathematical
      models for plaque distribution and aggregation. Image analysis plays a prominent
      role in this line of research, as stochastic image models and texture analysis
      have shown some success in the classification of subjects affected by Alzheimer's
      disease. It is concluded that relaxometric approaches seem to be a promising
      candidate for the task at hand, especially when combined with sophisticated image
      analysis, and when data from more than one time-point is available. There have
      been few longitudinal studies of mice models so far, so this direction of
      research warrants future efforts.

PMID- 19747157
TI  - Is increased mortality from Alzheimer's disease in Sweden a reflection of better
      diagnostics?
AB  - Mortality data were retrieved from the Swedish death registry for the years 1970
      2006. This report presents updated information on mortality from Alzheimer's
      disease (AD) through the year 2006, as well as a statistical model of AD
      mortality with predictive value. This model was developed based on a mortality
      risk function acting after a specific time point, either step-wise on the whole
      population or on an increasing part of it. Data collected in recent years
      indicate that mortality is increasing continuously amongst the oldest patients,
      while younger age-groups show more stable mortality rates. After fitting the
      statistical model to age-standardized mortality data it also gave age-specific
      rates that fit well with reported data without further adjustments in model
      parameters. The data and the corresponding model for AD mortality suggest that
      the ability of the body to protect itself from AD-related neurological damage has
      in general became increasingly impaired since about 1985. This impairment has
      mainly affected people 65 years of age and older since 1985; the model predicts
      that in 2020, the age-standardized mortality in Sweden will be 13/100,000 person
      years. The author concludes that the increasing mortality is real and not only a
      result of increasing use of the death classification code for AD.

PMID- 19747158
TI  - Amyloid deposition and inflammation in APPswe/PS1dE9 mouse model of Alzheimer's
      disease.
AB  - Alzheimer's disease (AD) is characterized by amyloid plaques and neurofibrillary
      tangles associated with chronic inflammation. APPswe/PS1dE9 is an AD mouse model
      bearing mutant transgenes of amyloid precursor protein and presenilin-1. Amyloid
      deposition is present in this mouse model at early stage of life. However, the
      progression of inflammation and its relationship with amyloid deposition have not
      been characterized. Here we showed that amyloid plaques were present at 4 months
      of age and increased with age. CD11b-positive microglia clusters appeared in
      hippocampus and neocortex at 4 months of age and increased with age. Clustered
      glial fibrillary acidic protein (GFAP)-positive astrocytes were observed in
      hippocampus and cortex after 6 months of age and increased with age. Double
      staining with CD11b/GFAP antibody and thioflavin S showed clustered microglia and
      astrocytes were in close association with amyloid plaques. Expression of TNF
      alpha was detected at 8 months of age, while IL-1 beta, IL-6 and MCP-1 at 10
      months. These cytokines increased with age. Double immunostaining of cell
      specific marker and cytokine indicated TNF-alpha, IL-1 beta, IL-6 and MCP-1 were
      expressed by activated microglia and a small part of activated astrocytes. MCP-1
      was also expressed by neurons, which support recent finding that MCP-1 expression
      was increased in neurons of AD patient. These results demonstrate amyloid plaques
      and its associated inflammatory response developed at early stage of life and
      progressively increased with age, both activated glia and neurons are involved in
      chronic inflammation in AD. APPswe/PS1dE9 model provides a mean for studying the
      mechanisms and novel therapeutics for AD.

PMID- 19747159
TI  - Agents complexing copper as a therapeutic strategy for the treatment of
      Alzheimer's disease.
AB  - The notion that a copper dysfunction is implicated in Alzheimer's disease (AD) is
      based on a number of observations from in vitro and clinical studies, as well as
      animal models. However, there is still significant controversy over whether it is
      an excess or a deficiency of copper to be involved in the pathogenesis of AD.
      Numerous studies support the hypothesis that an excess of copper contributes to
      AD, but experimental evidence in transgenic mouse models seems to suggest the
      contrary, and at least one clinical study shows that cognitive decline correlates
      positively with low copper levels. We have recently reported on a deregulation of
      the ceruloplasmin-copper relationship, specific to AD patients, consisting of an
      elevation of the copper pool not bound to ceruloplasmin, i.e. 'free' copper. This
      phenomenon could provide an explanation of the contrasting results obtained in
      clinical studies. Several clinical trials have been attempted in search of an
      anti-metal effect counteracting AD progression. Some of them have delivered
      encouraging results indicating that "metal protein attenuating compounds" can
      indeed alter positively the progression of the disease. This review summarizes
      these clinical studies and provides an overview of those in progress and in
      preparation.

PMID- 19747160
TI  - Microglial activation in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a devastating chronic neurodegenerative disease with
      currently no available disease modifying treatment. In recent years, the peptide
      amyloid-beta has been proposed as the major pathogenic force in the development
      and progression of AD. Microglia, the resident immune and phagocytic cells of the
      brain, are known to constantly scan brain tissue and to respond to various
      pathological stimuli. Thus, newly formed plaque composed of A beta seem to
      activate and recruit microglia in AD transgenic mice. However, the role of
      microglia is only poorly understood in AD. Microglia may act as a double-edged
      sword being either detrimental or protective depending on the context. In this
      mini-review, we discuss the importance of microglia and its receptors in
      neuroinflammation and plaque clearance. A possible disease modifying role of
      blood-borne monocytes, which are close relatives of bone-marrow derived
      microglia, will also be addressed.

PMID- 19747161
TI  - Intracranial MR dynamics in clinically diagnosed Alzheimer's disease: the
      emerging concept of "pulse wave encephalopathy".
AB  - As increasingly shown in neuropathological and predementia clinical studies,
      cognitive decline with altered intracranial dynamics can fulfill current clinical
      criteria of dementia of the Alzheimer's type (DAT) and there is a marked
      pathogenic complexity of this epidemic syndrome. Whereas structural studies only
      suggest the unexpected frequency of cerebrovascular changes in late life DAT,
      flow quantification MR sequences now offer a great opportunity of in vivo
      accurate analysis of cerebrovascular function. Their first applications have
      allowed development of a modern concept of the intracranial dynamics; a complex
      windkessel system allows two processes that are crucial to insure brain
      oxygenation and nutrition, a periodic systolic marked expansion of the
      intracranial blood compartment within the rigid cranial cavity on the one hand, a
      marked dampening of the arterial pulse wave before it reaches capillary level on
      the other hand. This modern concept has allowed better understanding of two
      archetypes of windkessel failure or so-called pulse wave encephalopathy, normal
      pressure hydrocephalus and subcortical arteriosclerotic encephalopathy. Dynamic
      MRI may now help to detect and classify distinct patterns of cerebrovascular
      dysfunction in DAT. This dynamic approach helps to understand the major
      association between aging and DAT as well as the increasingly recognized overlap
      between Alzheimer's pathology, normal pressure hydrocephalus and arteriosclerotic
      neurodegeneration. Evidence of such a great variety of disturbances in
      intracranial dynamics behind a single clinical syndrome of DAT can greatly impact
      therapeutic research on this devastating disorder.

PMID- 19747162
TI  - A possible new diagnostic biomarker in early diagnosis of Alzheimer's disease.
AB  - Early diagnosis in patients with Alzheimer's disease (AD) is of great importance
      since only a sufficient treatment in early stages of this disease helps to keep
      patients in an autonomous state for as long as possible. Until now, there is no
      single diagnostic biomarker for AD derived from material routinely obtained. In
      this study, proton nuclear magnetic resonance (1H-NMR) spectra of the
      cerebrospinal fluid (CSF) of AD patients were compared with 1H-NMR spectra of the
      CSF of healthy control subjects using a metabonomic approach. The 1H-NMR spectra
      of CSF of AD patients showed specific multiplets at 2.15 ppm and 2.45 ppm, which
      could not be detected in the majority (59.3% and 70.4%, respectively) of healthy
      control subjects (positive likelihood ratio (+LR) 2.33, 95% CI [1.46, 3.72],
      p<0.01; +LR 3.22, 95% CI [1.78, 5.78], p<0.01). Moreover, CSF 1H-NMR spectra of
      AD patients showed specific resonances at 7.03 ppm (+LR 3.38, 95% CI [1.60,
      7.14], p<0.05), 7.19 ppm (+LR 2.89, 95% CI [1.46, 5.74], p<0.05), 7.43 ppm (+LR
      3.15, 95% CI [1.47, 6.75], p<0.05), and at 7.91 ppm (+LR 3.38, 95% CI [1.60,
      7.14], p<0.01). CSF 1H-NMR spectroscopy is obviously a capable method for
      detection and quantification of substances in the CSF of AD patients even without
      the knowledge of molecular structures. These substances can be used as a
      biomarker in the early diagnosis of AD. We assume that this biomarker will
      simplify the diagnosis of AD, especially in early stages of the disease.

PMID- 19747163
TI  - An fMRI stroop task study of prefrontal cortical function in normal aging, mild
      cognitive impairment, and Alzheimer's disease.
AB  - Severe cortex lesions in the hippocampal, parahippocampal and medial temporal
      lobe (MTL) of Alzheimer's disease subjects have been observed by functional
      magnetic resonance imaging (fMRI) during memory task performance. To date, fMRI
      technology has not been used to investigate the frontal lobe function of
      Alzheimer's subjects. This study determines if fMRI can be used to assess altered
      prefrontal cortex activity during Stroop task performance in subjects wih mild
      cognitive impairment (MCI) and Alzheimer's disease (AD). Functional magnetic
      resonance imaging (fMRI) was performed on 9 healthy elderly controls, 9 subjects
      with mild cognitive impairment and 10 patients with Alzheimer's disease, to
      examine the prefrontal changes in fMRI activation in relation to the Stroop color
      word paradigm. In comparison with controls, MCI subjects showed distinctly
      increased cortex activity including: the dorsal anterior cingulate, bilateral
      middle and inferior frontal gyri, bilateral inferior parietal lobule, and the
      bilateral insular. In contrast, AD subjects exhibited decreased fMRI responses in
      the regions of the prefrontal cortex listed above. These results imply two
      different neurophysiological characteristics of MCI and AD. In MCI, a
      compensatory activity of the prefrontal cortex is observed, whereas in AD a
      dysfunction of the prefrontal cortex is indicated.

PMID- 19747164
TI  - Thyroid-hormone-dependent activation of the phosphoinositide 3-kinase/Akt cascade
      requires Src and enhances neuronal survival.
AB  - We have reported previously a non-genomic action of T3 (3,3',5-tri
      iodothyronine), which stimulates the PI3K (phosphoinositide 3-kinase)/Akt pathway
      via p85alpha, the regulatory subunit of PI3K, in human skin fibroblasts. The aim
      of the present study was to elucidate the mechanism by which T3 activates PI3K,
      and to investigate the physiological role of this T3 action in neuronal cells. We
      found that T3 activates PI3K/Akt through Src. First, T3 rapidly induced the
      activation of Src and Akt in N2a cells expressing TRalpha1 (thyroid hormone
      receptor alpha1; N2aTRalpha), and both were attenuated by either the addition of
      a Src inhibitor or Src siRNA. In contrast, a PI3K inhibitor could only block the
      activation of Akt. Secondly, T3 enhanced TRalpha1-p85alpha-Src complex formation,
      which was also abrogated by a Src inhibitor. The activation of Src and PI3K/Akt
      contributes to the anti-apoptotic effect of T3 in N2aTRalpha cells. Moreover, it
      was also observed in primary cerebral cortical neurons that T3 induced the
      activation of PI3K/Akt and suppressed serum-deprivation-induced apoptosis.
      Together, the findings of the present study demonstrate a novel non-genomic
      action of T3 on neuronal cell survival, and provide new insights into the
      mechanism underlying this action, which involves Src activation and TRalpha1
      p85alpha-Src complex formation.

PMID- 19747165
TI  - Mesothelin inhibits paclitaxel-induced apoptosis through the PI3K pathway.
AB  - Mesothelin, a secreted protein, is overexpressed in some cancers, but its exact
      function remains unclear. The aim of the present study was to evaluate the
      possible function of mesothelin. Real-time PCR, RT (reverse transcription)-PCR,
      cytotoxicity assays, proliferative assays, apoptotic assays by Hoechst staining,
      detection of active caspases 3 and 7 by flow cytometric analysis, and
      immunoprecipitation and immunoblotting were performed. Cancer tissues in
      paclitaxel-resistant ovarian cancer patients expressed higher levels of
      mesothelin as assessed using real-time PCR than paclitaxel-sensitive ovarian
      cancer patients (the mean crossing point value change of mesothelin was 26.9+/
      0.4 in the resistant group and 34.3+/-0.7 for the sensitive group; P<0.001).
      Mesothelin also protected cells from paclitaxel-induced apoptosis. The protein
      expression of Bcl-2 family members, such as Bcl-2 and Mcl-1, was significantly
      increased regardless of whether cells were treated with exogenous mesothelin or
      were mesothelin-transfectants. Furthermore, mesothelin-treated cells revealed
      rapid tyrosine phosphorylation of the p85 subunit of PI3K (phosphoinositide 3
      kinase) and ERK (extracellular-signal-regulated kinase) 1/2 for enhancing MAPK
      (mitogen-activated protein kinase) activity. The anti-apoptotic ability was
      suppressed and the expression of Bcl-2 family in response to mesothelin was
      altered by inhibiting PI3K activity, but not by inhibiting MAPK activity. Thus
      mesothelin can inhibit paclitaxel-induced cell death mainly by involving PI3K
      signalling in the regulation of Bcl-2 family expression. Mesothelin is a
      potential target in reducing resistance to cytotoxic drugs.

PMID- 19747166
TI  - Myosin is reversibly inhibited by S-nitrosylation.
AB  - Nitric oxide (NO*) is synthesized in skeletal muscle and its production increases
      during contractile activity. Although myosin is the most abundant protein in
      muscle, it is not known whether myosin is a target of NO* or NO* derivatives. In
      the present study, we have shown that exercise increases protein S-nitrosylation
      in muscle, and, among contractile proteins, myosin is the principal target of
      exogenous SNOs (S-nitrosothiols) in both skinned skeletal muscle fibres and
      differentiated myotubes. The reaction of isolated myosin with S
      nitrosoglutathione results in S-nitrosylation at multiple cysteine thiols and
      produces two populations of protein-bound SNOs with different stabilities. The
      less-stable population inhibits the physiological ATPase activity, without
      affecting the affinity of myosin for actin. However, myosin is neither inhibited
      nor S-nitrosylated by the NO* donor diethylamine NONOate, indicating a
      requirement for transnitrosylation between low-mass SNO and myosin cysteine
      thiols rather than a direct reaction of myosin with NO* or its auto-oxidation
      products. Interestingly, alkylation of the most reactive thiols of myosin by N
      ethylmaleimide does not inhibit formation of a stable population of protein-SNOs,
      suggesting that these sites are located in less accessible regions of the protein
      than those that affect activity. The present study reveals a new link between
      exercise and S-nitrosylation of skeletal muscle contractile proteins that may be
      important under (patho)physiological conditions.

PMID- 19747167
TI  - Differential regulation of adipocyte PDE3B in distinct membrane compartments by
      insulin and the beta3-adrenergic receptor agonist CL316243: effects of caveolin-1
      knockdown on formation/maintenance of macromolecular signalling complexes.
AB  - In adipocytes, PDE3B (phosphodiesterase 3B) is an important regulatory effector
      in signalling pathways controlled by insulin and cAMP-increasing hormones.
      Stimulation of 3T3-L1 adipocytes with insulin or the beta3-adrenergic receptor
      agonist CL316243 (termed CL) indicated that insulin preferentially
      phosphorylated/activated PDE3B associated with internal membranes (endoplasmic
      reticulum/Golgi), whereas CL preferentially phosphorylated/activated PDE3B
      associated with caveolae. siRNA (small interfering RNA)-mediated KD (knockdown)
      of CAV-1 (caveolin-1) in 3T3-L1 adipocytes resulted in down-regulation of
      expression of membrane-associated PDE3B. Insulin-induced activation of PDE3B was
      reduced, whereas CL-mediated activation was almost totally abolished. Similar
      results were obtained in adipocytes from Cav-1-deficient mice. siRNA-mediated KD
      of CAV-1 in 3T3-L1 adipocytes also resulted in inhibition of CL-stimulated
      phosphorylation of HSL (hormone-sensitive lipase) and perilipin A, and of
      lipolysis. Superose 6 gel-filtration chromatography of solubilized membrane
      proteins from adipocytes stimulated with insulin or CL demonstrated the
      reversible assembly of distinct macromolecular complexes that contained 32P
      phosphorylated PDE3B and signalling molecules thought to be involved in its
      activation. Insulin- and CL-induced macromolecular complexes were enriched in
      cholesterol, and contained certain common signalling proteins [14-3-3, PP2A
      (protein phosphatase 2A) and cav-1]. The complexes present in insulin-stimulated
      cells contained tyrosine-phosphorylated IRS-1 (insulin receptor substrate 1) and
      its downstream signalling proteins, whereas CL-activated complexes contained
      beta3-adrenergic receptor, PKA-RII [PKA (cAMP-dependent protein kinase)
      regulatory subunit] and HSL. Insulin- and CL-mediated macromolecular complex
      formation was significantly inhibited by CAV-1 KD. These results suggest that cav
      1 acts as a molecular chaperone or scaffolding molecule in cholesterol-rich lipid
      rafts that may be necessary for the proper stabilization and activation of PDE3B
      in response to CL and insulin.

PMID- 19747168
TI  - Uncoupling protein 1 inhibition by purine nucleotides is under the control of the
      endogenous ubiquinone redox state.
AB  - We studied non-esterified fatty acid-induced uncoupling of heterologously
      expressed rat UCP1 (uncoupling protein 1) in yeast mitochondria, as well as UCP1
      in rat BAT (brown adipose tissue) mitochondria. The proton-conductance curves and
      the relationship between the ubiquinone reduction level and membrane potential
      were determined in non-phosphorylating BAT and yeast mitochondria. The ADP/O
      method was applied to determine the ADP phosphorylation rate and the relationship
      between the ubiquinone reduction level and respiration rate in yeast
      mitochondria. Our studies of the membranous ubiquinone reduction level in
      mitochondria demonstrate that activation of UCP1 leads to a purine nucleotide
      sensitive decrease in the ubiquinone redox state. Results obtained for non
      phosphorylating and phosphorylating mitochondria, as the endogenous ubiquinone
      redox state was gradually varied by a lowering rate of the ubiquinone-reducing or
      ubiquinol-oxidizing pathways, indicate that the endogenous ubiquinone redox state
      has no effect on non-esterified fatty acid-induced UCP1 activity in the absence
      of GTP, and can only regulate this activity through sensitivity to inhibition by
      the purine nucleotide. At a given oleic acid concentration, inhibition by GTP
      diminishes when ubiquinone is reduced sufficiently. The ubiquinone redox state
      dependent alleviation of UCP1 inhibition by the purine nucleotide was observed at
      a high ubiquinone reduction level, when it exceeded 85-88%.

PMID- 19747170
TI  - Abstracts of the XXVII Annual Scientific Meeting of the British Blood Transfusion
      Society. September 10-12, 2009. Manchester, United Kingdom.

PMID- 19747169
TI  - Mapping the ligand-binding pocket of integrin alpha5beta1 using a gain-of
      function approach.
AB  - Integrin alpha5beta1 is a key receptor for the extracellular matrix protein
      fibronectin. Antagonists of human integrin alpha5beta1 have therapeutic potential
      as anti-angiogenic agents in cancer and diseases of the eye. However, the
      structure of the integrin is unsolved and the atomic basis of fibronectin and
      antagonist binding by integrin alpha5beta1 is poorly understood. In the present
      study, we demonstrate that zebrafish alpha5beta1 integrins do not interact with
      human fibronectin or the human alpha5beta1 antagonists JSM6427 and cyclic peptide
      CRRETAWAC. Zebrafish alpha5beta1 integrins do bind zebrafish fibronectin-1, and
      mutagenesis of residues on the upper surface and side of the zebrafish alpha5
      subunit beta-propeller domain shows that these residues are important for the
      recognition of the Arg-Gly-Asp (RGD) motif and the synergy sequence [Pro-His-Ser
      Arg-Asn (PHSRN)] in fibronectin. Using a gain-of-function analysis involving
      swapping regions of the zebrafish integrin alpha5 subunit with the corresponding
      regions of human alpha5 we show that blades 1-4 of the beta-propeller are
      required for human fibronectin recognition, suggesting that fibronectin binding
      involves a broad interface on the side and upper face of the beta-propeller
      domain. We find that the loop connecting blades 2 and 3 of the beta-propeller,
      the D3-A3 loop, contains residues critical for antagonist recognition, with a
      minor role played by residues in neighbouring loops. A new homology model of
      human integrin alpha5beta1 supports an important function for D3-A3 loop residues
      Trp157 and Ala158 in the binding of antagonists. These results will aid the
      development of reagents that block integrin alpha5beta1 functions in vivo.

PMID- 19747171
TI  - Strategies for reducing polypharmacy and other medication-related problems in
      chronic kidney disease.
AB  - Medication-related problems are very common in patients with chronic kidney
      disease (CKD). These problems are often avoidable and can result in detrimental
      patient consequences and high financial costs. Despite these risks, it is often
      medically necessary to prescribe multiple medications to treat the comorbid
      conditions that accompany CKD. In addition, patients' use of nonprescription
      medications and changes in pharmacokinetic and pharmacodynamic parameters may
      further contribute to medication-related problems in CKD, including drug
      interactions and the need for dosage adjustments. A structured medication
      assessment process is one approach to reducing the risks associated with
      medication-related problems. This multifaceted process involves a comprehensive
      medication history interview, structured therapy assessment, and open
      communication between members of the medical team. A detailed description of this
      process is provided to aid healthcare providers in addressing this important
      issue.

PMID- 19747172
TI  - Depression in end-stage renal disease: current advances and research.
AB  - Depression or the presence of significant depressive symptoms remains common in
      patients with end-stage renal disease (ESRD). It is thought that 20-30% of ESRD
      patients have significant depressive symptoms, although there are issues
      surrounding the assessment of depression among patients with physical illness.
      Screening tools may be useful in this setting to identify patients with low
      affect, accompanied by formal diagnostic approaches which are important to
      consider following a positive screen. Recent evidence highlights the impact of
      depression upon mortality, and its association with non-adherence and immune
      parameters, work that supports past investigations. Further studies are required
      to better our understanding of the mechanisms behind depression in patients with
      ESRD identifying both psychological and clinical antecedents. A focus on the
      treatment of depression is now critical given the evidence that depression
      impacts upon outcome in ESRD. Antidepressants seem effective, but the prevalence
      of negative side effect profiles and drug-drug interactions suggest a role for
      psychotherapeutic approaches. Of these, cognitive behavioral therapy shows real
      promise.

PMID- 19747173
TI  - An interesting case: retrograde blood flow from a LIMA sustaining hemodialysis
      via an AVF.
AB  - A case is described in which the inflow of a left radiocephalic arteriovenous
      fistula was being maintained by retrograde flow from a patent left internal
      mammary artery bypass graft, distal to a severe left subclavian artery stenosis.
      The clinical manifestations of this phenomenon were angina, lateral chest wall
      pain during dialysis, and distal hypoperfusion of the left hand. After stenting
      of the subclavian lesion, all symptoms resolved.

PMID- 19747174
TI  - Arterial interventions in arteriovenous access and chronic kidney disease: a role
      for interventional nephrologists.
AB  - The past decade has witnessed an evolution of the specialty of Nephrology in the
      United States to an interventional discipline. Traditionally, Interventional
      Nephrologists have focused on the venous side of an arteriovenous access.
      However, these specialists are beginning to include arterial disease related to
      renal patients under the purview of this specialty. Recent data have emphasized
      that inflow stenosis of an arteriovenous access frequently results in vascular
      access dysfunction. Peripheral vascular disease, resulting in distal
      hypoperfusion ischemia syndrome of the hand bearing the access, is similarly
      being recognized and managed more frequently by these experts. Two distinct
      entities, subclavian artery and renal artery stenosis, are also being addressed
      by interventional nephrologists. This article focuses on arterial interventions
      performed by interventional nephrologists and describes the epidemiology,
      techniques, and outcomes of arterial intervention as they relate to the care of
      patients with hemodialysis access and chronic kidney disease.

PMID- 19747175
TI  - Arterial angioplasty to treat hand ischemia in a radial-cephalic fistula.
AB  - A chronic hemodialysis patient was referred to interventional nephrology for
      evaluation of left hand pain. The patient had been receiving hemodialysis through
      a left radial-cephalic arteriovenous fistula and reporting hand pain during
      dialysis. Physical examination demonstrated cold hand and reduced capillary
      refill compared with the right hand. Clinical features, differential diagnosis,
      and physical examination findings were consistent with the diagnosis of hand
      ischemia due to dialysis access. Arteriography revealed >80% stenosis of the
      distal ulnar artery. Percutaneous balloon angioplasty successfully dilated the
      lesion with resolution of symptoms. Although uncommon, patients with forearm
      fistula can also experience symptoms of hand ischemia. This case demonstrates
      that in addition to the history, clinical features, differential diagnosis, and
      physical examination, arteriography is a vital step in the management of patients
      presenting with signs and symptoms of hand ischemia. Further, employment of a
      basic procedure (percutaneous balloon angioplasty) can successfully resolve the
      condition and maintain the dialysis access.

PMID- 19747176
TI  - Change--a new chapter in interventional nephrology.

PMID- 19747177
TI  - Arterial stent placement in arteriovenous dialysis access by interventional
      nephrologists.
AB  - Arterial stenoses in patients with arteriovenous dialysis access can create a
      variety of problems including access dysfunction, thrombosis, and hand ischemia.
      While percutaneous balloon angioplasty is largely successful in the management of
      arterial stenoses, elastic recoil can present a real predicament to this
      treatment. In this report, we present two cases of arterial stenosis that
      demonstrated elastic recoil after angioplasty and required endovascular stent
      insertion. Both cases were treated successfully without any complications on an
      outpatient basis. This report describes arterial stent placement in patients with
      arteriovenous access and discusses anticoagulation considerations in such cases.

PMID- 19747178
TI  - Chylothorax and chylopericardial tamponade in a hemodialysis patient with
      catheter-induced superior vena cava stenosis.
AB  - Chylothorax and chylopericardium refer to the presence of milky, triglyceride
      rich chylous fluid in the thoracic and pericardial spaces, respectively. Both
      conditions are extremely uncommon in end-stage renal disease patients on
      dialysis. We report the first known case of combined chylothorax and chylous
      pericardial tamponade in a dialysis patient associated with catheter-induced
      superior vena cava (SVC) stenosis. A successful outcome was achieved with
      drainage of both chylous effusions in combination with angioplasty of the SVC
      stenosis.

PMID- 19747179
TI  - Long-term complication rates and survival of peritoneal dialysis catheters: the
      role of percutaneous versus surgical placement.
AB  - Considerable controversy currently exists in the literature concerning the mode
      of catheter placement and its impact on the technical success of peritoneal
      dialysis (PD). We decided to compare the impact of the surgical versus the
      percutaneous insertion technique on peritoneal dialysis catheter (PDCs)
      complications and survival. Our study population comprised 152 patients in whom
      170 PDCs were inserted between January 1990 and December 2007 at the main PD unit
      on the island of Crete. Eighty four catheters were surgically placed (S group)
      and 86 were placed percutaneously by nephrologists (N group). The total
      experience accumulated was 4997 patient-months. The overall complications did not
      differ between the two groups. Only early leakage was more frequent in N group
      than S group (10.3 versus 1.9 episodes per 1000 patient-months; p < 0.001).
      However, it was easily treated and did not constitute a cause of early catheter
      removal. Catheter survival was 91.1%, 80.7%, and 73.2%, in the S group versus
      89.5%, 83.7%, and 83.7% for the N group at 1, 2, and 3 years, respectively (p =
      0.2). Catheter survival has significantly increased over the last decade. Factors
      positively affecting PDC survival appeared to be the use of mupirocin for exit
      site care and the utilization of the coiled type of catheter, practices
      implemented mainly after 1999. Peritonitis-free survival and patient survival
      were not associated with the mode of placement, while in Cox regression analysis,
      were longer in patients treated with automated PD. The placement mode did not
      affect PD outcomes. Percutaneous implantation proved a safe, simple, low cost,
      immediately available method for PDC placement and helped to expand our PD
      program.

PMID- 19747180
TI  - Advancing the metabolic theory of biodiversity.
AB  - A component of metabolic scaling theory has worked towards understanding the
      influence of metabolism over the generation and maintenance of biodiversity.
      Specific models within this 'metabolic theory of biodiversity' (MTB) have
      addressed temperature gradients in speciation rate and species richness, but the
      scope of MTB has been questioned because of empirical departures from model
      predictions. In this study, we first show that a generalized MTB is not
      inconsistent with empirical patterns and subsequently implement an eco
      evolutionary MTB which has thus far only been discussed qualitatively. More
      specifically, we combine a functional trait (body mass) approach and an
      environmental gradient (temperature) with a dynamic eco-evolutionary model that
      builds on the current MTB. Our approach uniquely accounts for feedbacks between
      ecological interactions (size-dependent competition and predation) and
      evolutionary rates (speciation and extinction). We investigate a simple example
      in which temperature influences mutation rate, and show that this single effect
      leads to dynamic temperature gradients in macroevolutionary rates and community
      structure. Early in community evolution, temperature strongly influences
      speciation and both speciation and extinction strongly influence species
      richness. Through time, niche structure evolves, speciation and extinction rates
      fall, and species richness becomes increasingly independent of temperature.
      However, significant temperature-richness gradients may persist within emergent
      functional (trophic) groups, especially when niche breadths are wide. Thus, there
      is a strong signal of both history and ecological interactions on patterns of
      species richness across temperature gradients. More generally, the successful
      implementation of an eco-evolutionary MTB opens the perspective that a process
      based MTB can continue to emerge through further development of metabolic models
      that are explicit in terms of functional traits and environmental gradients.

PMID- 19747181
TI  - Niches versus neutrality: uncovering the drivers of diversity in a species-rich
      community.
AB  - Ecological models suggest that high diversity can be generated by purely niche
      based, purely neutral or by a mixture of niche-based and neutral ecological
      processes. Here, we compare the degree to which four contrasting hypotheses for
      coexistence, ranging from niche-based to neutral, explain species richness along
      a body mass niche axis. We derive predictions from these hypotheses and confront
      them with species body-mass patterns in a highly sampled marine phytoplankton
      community. We find that these patterns are consistent only with a mechanism that
      combines niche and neutral processes, such as the emergent neutrality mechanism.
      In this work, we provide the first empirical evidence that a niche-neutral model
      can explain niche space occupancy pattern in a natural species-rich community. We
      suggest this class of model may be a useful hypothesis for the generation and
      maintenance of species diversity in other size-structured communities.

PMID- 19747182
TI  - Changes in habitat specificity of species at their climatic range boundaries.
AB  - Species are thought to have more restricted niches towards their range
      boundaries, although this has rarely been quantified systematically. We analysed
      transect data for 41 butterfly species along climatic gradients within Britain
      and show that 71% of species have broader niches at sites with milder winters.
      Shifts in habitat associations are considerable across most species' ranges;
      averaged across all 41 species, we estimate that if 26% of individuals were
      associated with the favoured habitat on the species' warmest transect, then 70%
      of individuals would be confined to this habitat on the species' coldest
      transect. Species with more southerly distributions in Britain showed the
      greatest changes in their habitat associations. We conclude that geographic
      variation in realized niche breadth is common and relatively large, especially
      near range boundaries, and should be taken into account in conserving species
      under changing climates.

PMID- 19747183
TI  - Willingness of nurses to report medication administration errors in southern
      Taiwan: a cross-sectional survey.
AB  - BACKGROUND: Underreporting of medication administering errors (MAEs) is a threat
      to the quality of nursing care. The reasons for MAEs are complex and vary by
      health professional and institution. AIMS: The purpose of this study was to
      explore the prevalence of MAEs and the willingness of nurses to report them.
      METHODS: A cross-sectional study was conducted involving a survey of 14 medical
      surgical hospitals in southern Taiwan. Nurses voluntarily participated in this
      study. A structured questionnaire was completed by 605 participants. Data were
      collected from February 1, 2005 to March 15, 2005 using the following
      instruments: MAEs Unwillingness to Report Scale, Medication Errors Etiology
      Questionnaire, and Personal Features Questionnaire. One additional question was
      used to identify the willingness of nurses to report medication errors: "When
      medication errors occur, should they be reported to the department?" This
      question helped to identify the willingness or lack thereof, to report incident
      errors. RESULTS: The results indicated that 66.9% of the nurses reported
      experiencing MAEs and 87.7% of the nurses had a willingness to report the MAEs if
      there were no consequences for reporting. The nurses' willingness to report MAEs
      differed by job position, nursing grade, type of hospital, and hospital funding.
      The final logistic regression model demonstrated hospital funding to be the only
      statistically significant factor. The odds of a willingness to report MAEs
      increased 2.66-fold in private hospitals (p = 0.032, CI = 1.09 to 6.49), and 3.28
      in nonprofit hospitals (p = 0.00, CI = 1.73 to 6.21) when compared to public
      hospitals. CONCLUSIONS: This study demonstrates that reporting of MAEs should be
      anonymous and without negative consequences in order to monitor and guide
      improvements in hospital medication systems.

PMID- 19747184
TI  - Association of increased serum acute-phase protein concentrations with
      reproductive performance in dairy cows with postpartum metritis.
AB  - BACKGROUND: It is known that quantification of bovine acute-phase proteins could
      routinely provide early diagnostic and prognostic information for monitoring herd
      health status. OBJECTIVE: The aim of this study was to test the hypothesis that
      haptoglobin (Hp) and serum amyloid A (SAA) have the potential for indicating
      uterine infection, mainly due to subclinical endometritis, which can seriously
      influence the reproductive performance in dairy cows. METHODS: A total of 264
      serum samples were collected from 24 Holstein dairy cows at defined intervals
      from 1 week prepartum to 6 months postpartum. Clinically healthy animals (Group
      1, n=6) were compared with 24 animals having acute puerperal metritis (Group 2,
      n=18) and with concentrations obtained from healthy heifers (baseline values,
      n=10). The concentrations of serum Hp and SAA were measured using a hemoglobin
      binding assay and Western blot analysis, respectively. Reproductive performance
      was assessed as the number of days open and the conception rate at the end of the
      study. RESULTS: Upper cut-off values for Hp and SAA concentrations in heifers
      were 130.9 microg/L and 51.9 microg/mL, respectively. Hp concentrations in Group
      2 were significantly higher than those in Group 1 at all time points (P<.001).
      Additionally, among the successfully pregnant animals, the number of days open
      was significantly higher in 6 cows with Hp >130.9 microg/mL (median=316 days)
      than in 11 cows with Hp < or =130.9 microg/mL (median=120 days) (P=.0024).
      CONCLUSIONS: Serum Hp and SAA concentrations can be used to recognize uterine
      infection in postpartum cows. The association between elevated Hp values and
      number of days open suggests Hp may also be a useful indicator of poor prognosis
      for reproductive performance.

PMID- 19747185
TI  - Epidemiology and burden of disease from Japanese encephalitis in Cambodia:
      results from two years of sentinel surveillance.
AB  - OBJECTIVES: To describe the results from two years of Japanese encephalitis (JE)
      sentinel surveillance in Cambodia. METHODS: Sentinel site surveillance for JE in
      children aged 15 years and under was implemented in Cambodia in mid-2006. It was
      integrated into the routine meningoencephalitis surveillance system. Six
      hospitals were selected as sentinel sites. Epidemiological information and
      diagnostic specimens were collected from each patient presenting with
      meningoencephalitis. Cerebrospinal fluid and sera were tested for presence of
      immunoglobulin M antibodies against JE and dengue viruses by an ELISA.
      Surveillance data from 2006 to 2008 were analysed. RESULTS: Of 586 patients
      presenting with meningoencephalitis, 110 (19%) were confirmed to have JE. The
      percentage of confirmed JE cases at individual sentinel sites ranged from 13% to
      35% of all meningoencephalitis cases. Mean age was 6.2 years, with 95% of JE
      cases in children aged 12 years and under. Cases occurred year-round in both 12
      month reporting periods. CONCLUSIONS: JE is an important cause of
      meningoencephalitis in Cambodian children. As JE is a vaccine-preventable
      disease, an immunization programme could result in a considerable reduction in
      morbidity and mortality from JE among children in Cambodia.

PMID- 19747186
TI  - Imbalance of pro- and antifibrogenic genes and bile duct injury in murine
      Schistosoma mansoni infection-induced liver fibrosis.
AB  - OBJECTIVES: The murine model of Schistosoma mansoni infection is characterized by
      strong fibrosis and little hepatocellular injury. The objective of this study was
      to evaluate the potential link between hepatic schistosomiasis and bile duct
      injury in relation to the expression of profibrotic cytokines and fibrosis
      related genes. METHODS: Hepatic schistosomiasis was induced via percutaneous
      infection of mice with 50 S. mansoni cercariae. Markers of fibrosis including
      matrixmetalloproteinases (MMPs) and tissue-inhibitors of metalloproteinases
      (TIMPs), as well as markers of bile duct injury (keratin-19, VCAM-1) were studied
      during 24 weeks after infection by RT-PCR and immunohistochemistry. RESULTS:
      Liver biochemistry revealed no differences in serum transaminase and alkaline
      phosphatase levels in infected and uninfected mice. Total liver hydroxyproline
      content was increased 5-fold (P < 0.05) after infection. Gene expression analysis
      revealed MMP-2 (12-fold, P < 0.05) and TIMP-1 (48-fold, P < 0.05) up-regulation
      after infection. The balance of MMP and TIMP was shifted towards TIMP. Bile ducts
      were engulfed by adjacent granulomas resulting in ductular proliferation (keratin
      19). VCAM-1 expression and inflammatory infiltrates were reduced. CONCLUSIONS:
      This study demonstrates that schistosomiasis is associated with (i) an imbalance
      of MMP-2 and TIMP-1 as key players of fibrogenesis and (ii) with secondary bile
      duct alterations leading to ductular proliferation possibly contributing to
      fibrosis.

PMID- 19747187
TI  - The possible involvement of salsolinol and hypothalamic prolactin in the central
      regulatory processes in ewes during lactation.
AB  - Salsolinol, a dopamine-related compound and prolactin-producing cells were found
      in the ovine hypothalamus. This study was designed to test the hypothesis that
      salsolinol, acting from the CNS level, is able to stimulate pituitary prolactin
      release as well as prolactin mRNA expression in the anterior pituitary cells (AP)
      and in the mediobasal hypothalamus (MBH) in lactating ewes. The
      intracerebroventricular infusions of salsolinol in two doses, total of 50 ng or 5
      MUg, were performed in a series of five 10-min infusions at 20-min intervals. All
      infusions were made from 12:30 to 15:00 and the pre-infusion period was from
      10:00 to 12.30 h. The prolactin concentration in plasma samples, collected every
      10 min, was determined by radioimmunoassay; prolactin mRNA expression in AP and
      MBH tissues was determined by real-time PCR. The obtained results showed that
      salsolinol infused at the higher dose significantly (p < 0.001) increased plasma
      prolactin concentration in lactating ewes, when compared with the concentration
      noted before the infusion and with that in lactating controls. In lactating ewes,
      the relative levels of prolactin mRNA expression in the AP and MBH were up to
      twofold and fivefold higher respectively than in non-lactating ewes (p < 0.05).
      In our experimental design, salsolinol did not significantly affect the ongoing
      process of prolactin gene expression in these tissues. We conclude that in ewes,
      salsolinol may be involved, at least, in the process of stimulation of prolactin
      release during lactation and that hypothalamic prolactin plays an important role
      in the central mechanisms of adaptation to lactation.

PMID- 19747188
TI  - Factors predicting transferal after psychiatric emergency management in the
      elderly.
AB  - AIMS: The purpose of this study was to examine the demographic and clinical
      characteristics that differentiate between elderly and non-elderly visitors in
      the psychiatric emergency room (ER), and to identify factors predicting
      transferal after psychiatric emergency management in the elderly. METHODS: Data
      were collected over four years for patients who visited the psychiatric ER. The
      elderly were defined as patients older than 65 years old. Demographic and
      clinical characteristics were analyzed using the chi(2)-test for categorical data
      and t-tests for continuous data. Multivariate logistic regressions were carried
      out to find predictive factors associated with being transferred to a general
      hospital for elderly visitors in the psychiatric ER. RESULTS: Elderly patients
      made up 3.4% of all included visitors (n = 243) during the four-year period. The
      mean number of visits for elderly visitors was 1.63 +/- 1.18, ranging from 1 to
      7. The chi(2)-test and the t-test indicated that the elderly visitors were
      different from controls in many demographic and clinical variables. Multivariate
      logistic regression analysis showed that being transferred to a general hospital
      for elderly visitors in the psychiatric ER was associated with age (odds ratio =
      1.32) and a greater number of previous psychiatric hospitalizations (odds ratio =
      1.42). Patients without a thought-form problem also required transferal to a
      general hospital more often in our study. CONCLUSIONS: The study suggested that
      elderly visitors in the psychiatric ER were a unique group, and specific
      considerations should be included in the intervention for these patients.

PMID- 19747189
TI  - Variability of perceived fatigue in primary biliary cirrhosis: implications for
      symptom assessment.

PMID- 19747190
TI  - A star-spangled liver.

PMID- 19747191
TI  - Surgical management of liver hydatidosis: a multicentre series of 1412 patients.
AB  - BACKGROUND: The management of hydatid liver disease (HLD) includes various
      nonsurgical and surgical treatment options. METHODS: The purpose of the present
      longitudinal study was to report the changes in surgical management and the
      consequent outcome of HLD patients in 10 referral surgical centres in Argentina
      from 1975 to 2007. The study result analysis was divided into two study periods
      (1975-1990 and 1991-2007). RESULTS: A total of 1412 patients underwent radical
      (Group 1: 396 patients), conservative (Group 2: 748 patients) or combined (Group
      3: 536 interventions in 268 patients) surgical procedures. The overall mortality
      and complication rate (Clavien I-IV) was 1.8 and 39% respectively. The
      complication rate was significantly lower in Group 1 (26%) compared with Group 2
      (45%) and Group 3 (42%) There was a significant decrease in mortality (2.3 vs.
      1%), complication (42 vs. 34%) and early reoperation (12 vs. 6%) rates between
      the first study part (918 patients) and the second study part (494 patients).
      During a median follow-up of 7 years, there was a significant decrease in the
      first part of this study in the late reoperation rate (8.4-3%) and in disease
      recurrence (9-1.6%). CONCLUSION: This large national observational multicentre
      series shows a significant improvement in surgical management of HLD in
      Argentina, with a decrease in mortality, morbidity, early and late reoperation
      and recurrence rates. A recent trend was observed in favour of an earlier
      diagnosis, less complicated clinical presentation and recent use of minimally
      invasive approaches.

PMID- 19747192
TI  - Infectious agents detected in the feces of diarrheic foals: a retrospective study
      of 233 cases (2003-2008).
AB  - BACKGROUND: Diarrhea is common in foals but there are no studies investigating
      the relative prevalence of common infectious agents in a population of
      hospitalized diarrheic foals. OBJECTIVES: To determine the frequency of detection
      of infectious agents in a population of hospitalized foals with diarrhea and to
      determine if detection of specific pathogens is associated with age, outcome, or
      clinicopathologic data. ANIMALS: Two hundred and thirty-three foals < or = 10
      months of age with diarrhea examined at a referral institution. METHODS:
      Retrospective case series. Each foal was examined for Salmonella spp., viruses,
      Clostridium difficile toxins, Clostridium perfringens culture, C. perfringens
      enterotoxin, Cryptosporidium spp., and metazoan parasites in feces collected at
      admission or at the onset of diarrhea. RESULTS: At least 1 infectious agent was
      detected in 122 foals (55%). Rotavirus was most frequently detected (20%)
      followed by C. perfringens (18%), Salmonella spp. (12%), and C. difficile (5%).
      Foals < 1 month of age were significantly more likely to be positive for C.
      perfringens (odds ratio [OR] = 15, 95% confidence interval [CI] = 3.5-66) or to
      have negative fecal diagnostic results (OR = 3.0, 95% CI = 1.7-5.2) than older
      foals. Foals > 1 month of age were significantly more likely to have Salmonella
      spp. (OR = 2.6, 95% CI = 1.2-6.0), rotavirus (OR = 13.3, 95% CI = 5.3-33), and
      parasites (OR = 23, 95% CI = 3.1-185) detected compared with younger foals.
      Overall 191 of the 223 foals (87%) survived. The type of infectious agent
      identified in the feces or bacteremia was not significantly associated with
      survival. CONCLUSIONS AND CLINICAL IMPORTANCE: In the population studied, foals
      with diarrhea had a good prognosis regardless of which infectious agent was
      identified in the feces.

PMID- 19747193
TI  - Fluticasone propionate aerosol is more effective for prevention than treatment of
      recurrent airway obstruction.
AB  - BACKGROUND: Efficacy of inhaled fluticasone propionate (FP) for management of
      recurrent airway obstruction (RAO) has only been evaluated after several weeks'
      treatment. OBJECTIVES: To compare efficacy of (1) 3-day treatments with FP to
      dexamethasone (DEX) for management of RAO; and (2) FP and DEX to no treatment in
      prevention of acute RAO exacerbations. ANIMALS: Nine RAO affected horses.
      METHODS: Crossover studies in RAO-affected horses compared (a) 3-day treatment of
      RAO exacerbation with FP (3 and 6 mg q12h) and DEX (0.1 mg/kg q24h) and (b) FP (6
      mg q12h) and DEX (0.1 mg/kg q24h) to no treatment for prevention of acute
      exacerbations of RAO. Treatment efficacy and unwanted effects were judged from
      maximal change in pleural pressure (DeltaPpl(max)), serum cortisol (COR),
      bronchoalveolar lavage (BAL) cytology, and subjective scores for respiratory
      distress and lameness. RESULTS: In treatment trial, DEX and FP (6 mg)
      significantly decreased DeltaPpl(max) by 48 and 72 hours, respectively; FP (3 mg)
      had no significant effect. DEX decreased COR more than did FP. In prevention
      trial, both DEX and FP (6 mg) prevented the increase in DeltaPpl(max) that
      occurred in untreated horses. Both treatments decreased COR to the same degree.
      FP and DEX had no effects on bronchoalveolar lavage fluid (BALF) cytology and
      there was no evidence of laminitis. CONCLUSIONS AND CLINICAL IMPORTANCE: FP (6 mg
      q12h) is as effective as DEX for prevention of acute exacerbations of RAO and
      lower doses should be evaluated. High-dose FP is not as effective as DEX for
      treatment of RAO exacerbations.

PMID- 19747194
TI  - Surfactant protein C in canine pulmonary fibrosis.
AB  - BACKGROUND: Canine pulmonary fibrosis (CPF) occurs most commonly in West Highland
      White Terriers. The differing incidences of CPF among dog breeds suggest that
      genetic factors contribute to its pathophysiology. Pulmonary fibrosis in humans
      is associated with mutations in the gene coding for lung surfactant protein C (SP
      C) (SFTPC). HYPOTHESIS/OBJECTIVES: To investigate the histopathologic changes and
      SP-C composition and genetic structure in dogs with CPF. ANIMALS: Five dogs with
      PF, 2 dogs with other lung diseases, and 3 healthy dogs. METHODS: Lung tissue
      from dogs with clinically suspected CPF and 5 control cases was analyzed
      histopathologically. Bronchoalveolar lavage fluid (BALF) collected postmortem
      from 3 terriers with histopathologically confirmed pulmonary fibrosis and the 5
      controls were analyzed by Western blots, and the exons of SFTPC were sequenced
      for 2 dogs with PF and 1 dog with other lung disease. RESULTS: SP-C could not be
      detected in BALF of 1 dog with PF, although SP-B was present. A mutation was
      detected in SFTPC exon 5 of this dog. From 2 dogs with PF and in all 5 control
      dogs SP-B and SP-C were detected in BALF. CONCLUSIONS: Taken together, the
      results indicate that canine and human lung fibrosis share histopathologic
      features and that analysis of SP-C and its gene in a larger set of dogs with PF
      is warranted.

PMID- 19747195
TI  - Neuroaxonal dystrophy associated with cerebellar dysfunction in a 5-month-old
      Pony of the Americas colt.

PMID- 19747196
TI  - Self-reported severity of taste disturbances correlates with dysfunctional grade
      of TMD pain.
AB  - Altered central neural processing of sensory information may be associated with
      temporomandibular disorders (TMD) pain. The objectives of this study were to
      compare the prevalence of self-reported taste disturbances in TMD pain patients
      and in a control population, and to determine whether frequency of taste
      disturbances was correlated with dysfunctional grade of TMD pain. Subjects were
      2026 people within a German population sample and 301 consecutive TMD patients
      diagnosed using the Research Diagnostic Criteria. Taste disturbances were
      measured using two questions from the Oral Health Impact Profile. Dysfunctional
      grade of TMD pain was measured with the Graded Chronic Pain Scale. A two-sample
      test of proportions revealed that TMD patients reported a greater frequency of
      taste disturbances, 6%, than did the general population subjects, 2% (P < 0.001).
      Moreover, the frequency of taste disturbances correlated with the dysfunctional
      grade of TMD pain. For each 1 unit increase in taste disturbance, the odds of
      observing a higher grade of TMD pain increased by 29% (95% CI: 3-63%, P = 0.03).
      Analysis by individual taste question and adjustment for age and gender did not
      substantially affect the results. These findings are consistent with a central
      neural dysfunction in TMD pain and suggest that a common neural substrate may
      underlie sensory disturbances of multiple modalities in chronic pain patients.
      Further research regarding taste disturbances and trigeminally mediated pains
      such as in TMD is warranted.

PMID- 19747197
TI  - Structured review: evaluating the effectiveness of nurse case managers in
      improving health outcomes in three major chronic diseases.
AB  - AIM: This paper presents the findings of a review and appraisal of the evidence
      for the effectiveness of nurse case management in improving health outcomes for
      patients living either with Diabetes, Chronic Obstructive Pulmonary Disease or
      Coronary Heart Disease. BACKGROUND: Long term chronic health conditions provide
      some of the greatest challenges to western health care systems. In the UK, three
      of the most significant chronic conditions are Diabetes, Chronic Obstructive
      Pulmonary Disease and Coronary Heart Disease. Patients with these long term
      conditions are high users of health services who often receive unplanned, poorly
      co-ordinated, ad-hoc care in response to an exacerbation or crisis. To counter
      this, the nurse case manager is identified as a central aspect of improving care
      for these patients. However, the evidence for the effectiveness of nurse case
      management in improving health outcomes for the chronically ill is scarce.
      DESIGN: A structured review of the literature. METHOD: The review was undertaken
      focussing on studies that evaluated nurse case management with one or all of the
      three major long term chronic conditions. A total of 108 papers were initially
      reviewed and filtered to leave 75 citations that were appraised. About 18 papers
      were finally included in the review and subject to thematic analysis based on the
      health outcomes evaluated in the studies. RESULTS: Significantly positive results
      were reported for nurse case management impact on five health outcomes;
      'objective clinical measurements', 'quality of life and functionality', 'patient
      satisfaction', 'adherence to treatment' and 'self care and service use'.
      RELEVANCE TO CLINICAL PRACTICE: The evidence generated in this review suggests
      that nurse case managers have the potential to achieve improved health outcomes
      for patients with long term conditions. Further research is required to support
      role development and create a more targeted approach to the intervention.

PMID- 19747198
TI  - Stress, perceived support, resourcefulness and depressive symptoms in Taiwanese
      adolescents.
AB  - AIMS AND OBJECTIVE: This study investigated (1) the prevalence of self-reported
      depressive symptoms among first-year students at an Institute of Technology in
      southern Taiwan; (2) whether perceived support and resourcefulness were
      associated with these adolescents' depressive symptoms and (3) the moderating and
      mediating effects of learned resourcefulness on the relationship between
      stressors and the adolescents' depressive symptoms. BACKGROUND: An individual
      with adequate social support or resourcefulness may see stressors as less
      threatening or be more resilient in dealing with stressors compared with
      depressed individuals. The prevalence of depression in the global population
      increased rapidly during this past decade and consequently may have had a
      negative impact on population health outcomes. Among adolescents there has
      recently been an increased incidence of depression-related suicide reports.
      DESIGN: A cross-sectional, correlational design. METHOD: Adolescents (n = 913)
      were recruited to complete the following: the SDI in Chinese, the Inventory of
      Social Supportive Behaviours Scale - Modified and the Self-Control Schedule. Data
      analysis consisted of Pearson correlation and multiple regression analysis.
      Results. The prevalence of depression among participants was 13.4%. Participants
      who were younger, expressed lower satisfaction with their grades, perceived their
      health as worse, described peer relationship problems and exhibited smoking
      behaviour were more likely to have depressive symptoms. We observed five
      partially mediating effects of resourcefulness on stressors (age, perceived
      health, peer relationships, grades satisfaction and smoking behaviour) and
      depressive symptoms and one moderating effect of resourcefulness on the
      relationship between peer and depressive symptoms. CONCLUSIONS: Learned
      resourcefulness may play a critical role in decreasing depressive symptoms.
      RELEVANCE TO CLINICAL PRACTICE: These findings offer healthcare providers and
      educators information about the need for possible cognitive-behavioural
      interventions that could improve adolescents' relationships with their peers,
      enhance their satisfaction of grades and moderate or prevent depressive symptoms
      among this population. Moreover, it might decrease the prevalence of adolescent
      suicide.

PMID- 19747199
TI  - Stakeholder views on the impact of nurse prescribing on dermatology services.
AB  - AIM: To explore stakeholder views on the impact of nurse prescribing on
      dermatology services. BACKGROUND: Nurse led care enhances the services that
      dermatology patients receive. Research indicates that care delivered by nurse
      prescribers can improve efficiency and access to medicines. There is no evidence
      exploring the impact of nurse prescribing on the configuration of dermatology
      services. DESIGN: Case study. METHOD: A collective case study of 10 practice
      settings across England where nurses prescribed medicines for dermatology
      patients. A thematic analysis of semi-structured interview data collected during
      2006 and 2007. Participants were qualified nurse prescribers, administrative
      staff, doctors and non-nurse prescribers. FINDINGS: Nurse prescribing was
      reported to support and facilitate the modernisation of dermatology services. It
      enabled nurses to make effective use of their knowledge and skills, overcome
      delays in treatment and provide faster access to medicines. However several
      organisational issues restricted the success of the initiative. CONCLUSION: Nurse
      prescribing is successfully being used to support and deliver a range of services
      to dermatology patients. Stakeholders reported that both patients and staff had
      benefited by the adoption of this role by nurses. However issues over support and
      access to CPD and capacity of the workforce were identified as potential barriers
      which could affect the contribution of nurse prescribing to dermatology patients.
      RELEVANCE TO CLINICAL PRACTICE: Nurse prescribing contributes to the services
      provided to dermatology patients; Nurse supplementary prescribing contributes to
      the ability of dermatology nurse specialists to work in teams and prescribe
      complex medicines; Provision of adequate support and strategic planning are
      essential if the impact of nurse prescribing is to be fully realised.

PMID- 19747200
TI  - Anxiety as a factor influencing satisfaction with emergency department care:
      perspectives of accompanying persons.
AB  - AIM: To measure levels of anxiety among people accompanying consumers to the
      emergency department and to explore how anxiety influences satisfaction with
      care. BACKGROUND: When people seek treatment in an emergency department they are
      often accompanied by a next-of-kin, family member or friend. While the
      accompanying person plays a vital role in providing psycho-social support to
      consumers, little is known about how they perceive the quality of care. Learning
      more about how accompanying persons perceive care may inform the development of
      strategies to enhance communication processes between staff, consumers and
      accompanying persons. DESIGN; A prospective cross-sectional survey design.
      METHODS: Data were collected from a consecutive sample of accompanying persons at
      one Australian metropolitan teaching hospital. Of all eligible individuals
      approached, 128/153 (83.7%) returned completed questionnaires. The questionnaire
      comprised a series of open- and close-ended questions about perceptions of
      medical need, urgency and satisfaction with the overall visit. Anxiety was
      assessed using the Visual Analogue Scale for Anxiety (VAS-A). RESULTS: There was
      a significant association between the accompanying person's levels of anxiety and
      satisfaction at point of discharge. In the satisfied group, mean VAS-A scores
      were 17.4 (SD 17.5) compared to 42.9 (SD 26.6) in the not satisfied group (p =
      0.011). Moreover, those participants who were not satisfied with the visit did
      not show a significant reduction in VAS-A scores from triage to point of
      discharge. CONCLUSION: The lower the level of anxiety reported by accompanying
      persons when leaving the emergency department, the more satisfied they are likely
      to be with their emergency department visit. Ultimately, well informed and
      confident accompanying persons are beneficial for ensuring quality patient
      support. RELEVANCE TO CLINICAL PRACTICE: Asking accompanying persons about their
      anxiety level before discharge gives them the opportunity to pose clarifying
      questions and is, therefore, an effective way of improving their satisfaction
      with the emergency department visit.

PMID- 19747201
TI  - Increased prevalence of prolonged QT interval in males with primary or secondary
      hypogonadism: a pilot study.
AB  - Symptoms and signs of male hypogonadism span all organ systems, including the
      cardiovascular apparatus. The electrocardiographic QT interval reflects cardiac
      ventricular repolarization and, if prolonged, increases the risk of malignant
      arrhythmias. QT interval duration is similar in boys and girls during childhood,
      but shortens in males after puberty and experimental studies suggest that
      testosterone is a major contributor to shortening of QT interval in men. The aim
      of the present pilot study was to assess the duration of ventricular
      repolarization in adult males with primary or secondary hypogonadism. Standard
      ECG recordings were performed in 26 men (mean age 39.2 +/- 2.17 years) with
      pituitary or testicular hypogonadism and repeated in 15 patients during
      testosterone replacement. Twenty-six age-matched control men were also analysed.
      Measured QT intervals were corrected for heart rate according to Bazzett's
      formula (QTc = QT/radical RR interval). The prevalence of prolonged QTc was
      considerably higher in hypogonadal patients (four of 26 men) than in control men
      (none, p < 0.05) and in the general, healthy population (<2.5%). QTc interval
      normalized on hormone replacement therapy in the four patients presenting
      prolonged QTc in the hypogonadal state. Heart rate and left ventricular mass did
      not differ among the two groups and no known QT-prolonging factor was apparent in
      patients with abnormal QTc interval. In conclusion, a high number prolonged QT
      interval measurements was observed in hypogonadal men who may therefore be at
      increased risk for cardiac arrhythmias. This observation reveals an additional
      feature of male hypogonadism, which may benefit from testosterone replacement
      therapy.

PMID- 19747202
TI  - Papular hyperplasia of the follicular infundibulum after intense pulsed light
      treatment for photoaging.

PMID- 19747203
TI  - A novel ARX phenotype: rapid neurodegeneration with Ohtahara syndrome and a
      dyskinetic movement disorder.
AB  - ARX mutations are associated with variable clinical phenotypes. We report a new
      neurodegenerative phenotype associated with a known ARX mutation and causing
      early abnormal neurodevelopment, a complex movement disorder, and early infantile
      epileptic encephalopathy with a suppression-burst pattern (Ohtahara syndrome). A
      male infant presented at age 5 months with a dyskinetic movement disorder, which
      was initially diagnosed as infantile spasms. Clinical deterioration was
      accompanied by progressive cortical atrophy with a reduction in white matter
      volume and resulting in death in the first year of life; such a rapidly
      progressive and severe phenotype has not previously been described. ARX mutation
      testing should be undertaken in children aged less than 1 year with Ohtahara
      syndrome and a movement disorder, and in infants with unexplained
      neurodegeneration, progressive white matter loss, and cortical atrophy.

PMID- 19747204
TI  - The clinical presentation of mitochondrial diseases in children with progressive
      intellectual and neurological deterioration: a national, prospective, population
      based study.
AB  - AIM: Our aim was to study the clinical presentation, mode of diagnosis, and
      epidemiology of mitochondrial disorders in children from the UK who have
      progressive intellectual and neurological deterioration (PIND). METHOD: Since
      April 1997, we have identified patients aged 16 years or younger with suspected
      PIND through the monthly notification card sent to all UK consultant
      paediatricians by the British Paediatric Surveillance Unit. Clinical details
      obtained from reporting paediatricians are classified by an Expert Group.
      RESULTS: By July 2008, 2493 cases of PIND had been reported, among which there
      were 112 children (69 males, 43 females) with mitochondrial diseases presenting
      between birth and 14 years 7 months (median 12mo), divided into 13 subgroups. In
      some instances, clinical features were characteristic of mitochondrial disease,
      but many children presented non-specifically with combinations of developmental
      delay, hypotonia, failure to thrive, and seizures; 16 children had multisystem
      disease at presentation. Mortality was high: 40 children had died. Blood and/or
      cerebrospinal fluid lactate measurements were abnormal in 87 children, and 47 of
      78 brain magnetic resonance images showed increased basal ganglia signal.
      Definite diagnoses were usually made by muscle enzyme or genetic studies.
      INTERPRETATION: This is a unique population-based study of the mitochondrial
      disorders that cause childhood neurodegenerative disease. It provides detailed
      information about the clinical presentation and investigation of these complex
      cases.

PMID- 19747205
TI  - Leisure activities for 6 to 12-year-old children with cerebral palsy.

PMID- 19747206
TI  - Congenital perisylvian dysfunction - is it a spectrum?

PMID- 19747207
TI  - Measuring mobility limitations in children with cerebral palsy: interrater and
      intrarater reliability of a mobility questionnaire (MobQues).
AB  - AIM: The objective of this study was to assess the reliability of a mobility
      questionnaire (MobQues) that was developed to measure the mobility limitations of
      children with cerebral palsy (CP) as rated by their parents. A clinical version
      of the questionnaire, consisting of 47 items (MobQues47), is available, as well
      as a research version with 28 items for a specific population (MobQues28). Total
      scores are expressed on a scale of 0 to 100. METHOD: We assessed the interrater
      reliability between both parents of 289 children with CP (168 males, 121 females,
      age range 2-13 y, Gross Motor Function Classification System levels I-IV) and the
      intrarater reliability within a subgroup of 38 parents (of 23 children) who
      completed the MobQues twice. RESULTS: For the interrater reliability, high
      intraclass correlation coefficients (ICCs) were found for the MobQues47 (ICC
      0.92) and MobQues28 (ICC 0.87). The standard error of measurement (SEM) was 7.8
      and 8.9 respectively. As expected, the intrarater reliability was higher, as
      represented by higher ICCs (0.96-0.99) and lower SEMs (3.5-4.9) for both MobQues
      versions. INTERPRETATION: The results of this study indicate that the MobQues is
      a reliable instrument to measure the mobility limitations of children with CP.

PMID- 19747208
TI  - Reading performance correlates with white-matter properties in preterm and term
      children.
AB  - AIM: We used diffusion tensor imaging to investigate the association between
      white-matter integrity and reading ability in a cohort of 28 children. Nineteen
      preterm children (14 males, five females; mean age 11 y 11 mo [SD 1 y 10 mo],
      mean gestational age 30.5 wks (SD 3.2), mean birthweight was 1455 g [SD 625]);
      and nine term children (five males, four females; mean age 12 y 8 mo [SD 2 y 5
      mo], mean gestational age 39.6 wks (SD 1.2), and mean birthweight 3877 g [SD
      473]). METHOD: We tested whether fractional anisotropy in a left hemisphere
      temporoparietal region and in the corpus callosum correlates with birthweight and
      scores on the following three subtests of the Woodcock-Johnson III Tests of
      Achievement: word identification, word attack, and passage comprehension.
      RESULTS: Preterm children had lower reading scores than a comparison group for
      all reading subtests (p<0.05). We found significant correlations between
      birthweight and fractional anisotropy in the whole corpus callosum (p=0.001), and
      between fractional anisotropy and reading skill in the genu (p=0.001) and body
      (p=0.001) of the corpus callosum. The correlation between reading skill and
      fractional anisotropy in a left temporoparietal region previously associated with
      reading disability was not significant (p=0.095). INTERPRETATION: We conclude
      that perinatal white-matter injury of the central corpus callosum may have long
      term developmental implications for reading performance.

PMID- 19747209
TI  - Calcineurin deficiency decreases inflammatory lesions in transforming growth
      factor beta1-deficient mice.
AB  - Transforming growth factor (TGF) beta1) is an immunoregulatory cytokine involved
      in self-tolerance and lymphocyte homeostasis. Tgfb1 knock-out (KO) mice develop
      severe multi-focal autoimmune inflammatory lesions due to [Ca(2+)]i deregulation
      in T cells, and die within 3 weeks after birth. Because the calcineurin inhibitor
      FK506 inhibits the hyperresponsiveness of Tgfb1(-/-) thymocytes, and because
      calcineurin Abeta (CNAbeta)-deficient mice do not reject allogenic tumours, we
      have generated Tgfb1(-/-) Cnab(-/-) mice to address whether CNAbeta deficiency
      prevents T cell activation and inflammation in Tgfb1(-/-) mice. Here we show that
      in Tgfb1(-/-) Cnab(-/-) mice inflammation is reduced significantly relative to
      that in Tgfb1(-/-) mice. However, both CD4(+) and CD8(+) T cells in double knock
      out (DKO) mice are activated, as revealed by up-regulation of CD11a lymphocyte
      function-associated antigen-1 (LFA-1), CD44 and CD69 and down-regulation of
      CD62L. These data suggest that deficiency of CNAbeta decreases inflammatory
      lesions but does not prevent activation of autoreactive T cells. Also Tgfb1(-/-)
      T cells can undergo activation in the absence of CNAbeta, probably by using the
      other isoform of calcineurin (CNAalpha) in a compensatory manner. CNAbeta
      deficient T cells undergo spontaneous activation in vivo and are activated upon
      anti-T cell receptor stimulation in vitro. Understanding the role of calcineurin
      in T cell regulation should open up new therapeutic opportunities for
      inflammation and cancer.

PMID- 19747210
TI  - Chemokines and common variable immunodeficiency; possible contribution of CCL19,
      CCL21 and CCR7 to immune dysregulation.
AB  - Common variable immunodeficiency (CVID) is a heterogeneous syndrome characterized
      by defective immunoglobulin production and high frequency of bacterial
      infections, autoimmunity and manifestations of chronic inflammation. The
      homeostatic chemokines CCL19 and CCL21 and their receptor CCR7 are associated
      with modulation of inflammatory responses. CVID patients have decreased
      proportions of CCR7(+) T cells in peripheral blood and we hypothesized a further
      dysregulation of CCL19/CCL21/CCR7 in CVID. Serum levels of CCL19 and CCL21 were
      compared in CVID patients and controls. T cell expression of CCR7 was related to
      clinical characteristics in CVID patients. Spleens extirpated from CVID patients
      were analysed for expression of CCL19, CCL21 and CCR7. Peripheral blood
      mononuclear cells (PBMC) from CVID patients and controls were analysed for
      cytokine response on stimulation with CCL19 and CCL21. The main findings were:
      (i) CVID patients have raised serum levels of CCL19 and CCL21 independently of
      features of chronic inflammation; (ii) CCL19 and CCR7 have similar expression in
      spleens from CVID patients and controls, while CCL21 is variably down-regulated
      in spleens from patients; (iii) T cell expression of CCR7 is particularly low in
      patients characterized by chronic inflammation in vivo; and (iv) PBMC from CVID
      patients had attenuated cytokine response to stimulation with CCL19 and CCL21.
      CVID patients have raised circulatory levels of CCL19 and CCL21, and an
      attenuated cytokine response to stimulation with these chemokines. Because CCR7,
      CCL19 and CCL21 are key mediators balancing immunity and tolerance in the immune
      system, the abnormalities of these mediators might contribute to the profound
      immune dysregulation seen in CVID.

PMID- 19747211
TI  - Ultrasound measures of muscle thickness: intra-examiner reliability and influence
      of body position.
AB  - Ultrasound is an inexpensive and practical alternative to gold standard measures
      of muscle mass. Changes in body position may lead to intra-muscular fluid shifts
      that may affect the reliability of ultrasound measures. We assessed test-retest
      reliability of ultrasound measures of muscle thickness and the effect of position
      on these measures. Measures of muscle thickness were made from B-mode ultrasound
      images in 18 healthy participants. Repeated measurements were made by one
      examiner from two participant positions; standing and recumbent, from 18
      anatomical sites. Results demonstrated high test-retest reliability for measures
      taken in both participant positions [intra-class coefficient (ICC) scores 0.65 to
      0.94], except for the recumbent posterior lower leg measures (ICC 0.34).
      Recumbent measures were significantly smaller than those taken with participants
      standing. Length of time participants spent lying down did not significantly
      affect measures, indicating that any changes in intra-muscular fluid related to
      the time spent recumbent are negligible.

PMID- 19747212
TI  - Signalling through TLR2/MyD88 induces differentiation of murine bone marrow stem
      and progenitor cells to functional phagocytes in response to Candida albicans.
AB  - We have previously demonstrated that inactivated yeasts and hyphae of Candida
      albicans induce in vitro the proliferation of murine haematopoietic stem and
      progenitor cells (HSPCs, sorted as LKS cells: Lin(-) c-Kit(+) Sca-1(+)) as well
      as their differentiation to lineage-positive cells, through a MyD88-dependent
      pathway. In this work, we have found that this process is mainly mediated by
      TLR2, and that expanding cells express myeloid and not lymphoid markers.
      Incubation of long-term repopulating HSCs (Lin(-) CD105(+) and Sca-1(+)) with C.
      albicans yeasts resulted in their proliferation and up regulation of the common
      myeloid progenitors (CMPs) markers, CD34 and FcgammaRII/III, by a TLR2/MyD88
      dependent signalling pathway. In addition, this TLR2/MyD88 signalling promotes
      the differentiation of CMPs and granulocyte and macrophage progenitors (GMPs)
      into cells with the morphology of macrophages and neutrophils, characterized by
      an increase in the expression of CD11b, F4/80 and Ly6G, independently of the
      presence of growth and differentiation factors. These differentiated cells were
      able to phagocytose C. albicans yeasts and to produce proinflammatory cytokines.
      In conclusion, C. albicans may be sensed by TLRs on haematopoietic stem and
      progenitor cells to promote the host capability for rapidly replenishing myeloid
      cells that constitute the first line of defence against C. albicans.

PMID- 19747214
TI  - First isolation of Legionella species, including L. pneumophila serogroup 1, in
      Greek potting soils: possible importance for public health.
AB  - A total of 21 Legionella isolates were recovered from six out of 22 samples of
      potting soil from the Athens area, Greece. Legionella pneumophila (serogroups 1
      and 2-15) and species and serotypes included in the group of L. longbeachae
      serogroups 1 and 2, L. bozemanii serogroups 1 and 2, L. dumoffii, L. gormanii, L.
      jordanis, L. micdadei and L. anisa were isolated on BCYEalpha agar containing
      cysteine, GVPC and natamycin and on BCYEalpha agar containing cysteine, Wadowsky
      Yee supplement and natamycin. The bacterial load was 4000-120 000 CFU/g of
      potting soil. The isolation of L. pneumophila serogroup 1 from Greek potting
      soils is reported here for the first time.

PMID- 19747213
TI  - Crohn's disease-associated adherent-invasive E. coli are selectively favoured by
      impaired autophagy to replicate intracellularly.
AB  - Ileal lesions in Crohn's disease (CD) patients are colonized by pathogenic
      adherent-invasive Escherichia coli (AIEC) able to invade and to replicate within
      intestinal epithelial cells. Recent genome-wide association studies have
      highlighted the autophagy pathway as being associated with CD risk. In the
      present study we investigated whether defects in autophagy enhance replication of
      commensal and pathogenic Escherichia coli and CD-associated AIEC. We show that
      functional autophagy limits intracellular AIEC replication and that a
      subpopulation of the intracellular bacteria is located within LC3-positive
      autophagosomes. In IRGM and ATG16L1 deficient cells intracellular AIEC LF82
      bacteria have enhanced replication. Surprisingly autophagy deficiency did not
      interfere with the ability of intracellular bacteria to survive and/or replicate
      for any other E. coli strains tested, including non-pathogenic, environmental,
      commensal, or pathogenic strains involved in gastro enteritis. Together these
      findings demonstrate a central role for autophagy restraining Adherent-Invasive
      E. coli strains associated with ileal CD. AIEC infection in patients with
      polymorphisms in autophagy genes may have a significant impact on the outcome of
      intestinal inflammation.

PMID- 19747216
TI  - Examination of tunnelled haemodialysis catheters using scanning electron
      microscopy.
AB  - Tunnelled haemodialysis catheters (t-HDC) are prone to colonization by
      microorganisms, resulting in increased morbidity and mortality. A previous study
      concluded that all culture-negative catheters removed from cancer patients were
      colonized by microbial biofilms when examined by scanning electron microscopy
      (SEM). Examination of t-HDC by SEM has not been published before. A total of 44
      segments (0.5 cm each) from 11 ex-vivo t-HDC were examined by SEM prior to
      endoluminal brushing and quantitative culture to determine their colonization
      status. Endoluminal brushing yielded a positive culture from two catheters.
      Methicillin-sensitive Staphylococcus aureus was grown from one catheter and a
      Streptococcus species was cultured from the second. SEM examination revealed
      universal endoluminal coverage by adherent biological material (ABM), which was
      composed of fibrin, platelets and other host-derived products. However, bacterial
      cells were visible on the two culture-positive catheters and on two out of nine
      culture-negative catheters, and were possibly present on one culture-negative
      catheter. In conclusion, in this study the prevalence of microbial colonization
      of ex vivo t-HDC was 18% using the endoluminal brushing technique and 36% when
      examined by SEM. The previously reported universal microbial colonization of
      central venous catheters is likely to represent coverage by ABM rather than by
      microbial biofilms.

PMID- 19747215
TI  - Can C-reactive protein, procalcitonin and mid-regional pro-atrial natriuretic
      peptide measurements guide choice of in-patient or out-patient care in acute
      pyelonephritis? Biomarkers In Sepsis (BIS) multicentre study.
AB  - Whereas C-reactive protein (CRP), procalcitonin (PCT) and mid-regional pro-atrial
      natriuretic peptide (ANP) may be of use at the bedside in the management of adult
      patients with infectious disorders, their usefulness has not been established in
      the setting of acute pyelonephritis. To assess the effectiveness of CRP, PCT and
      ANP measurements in guiding emergency physicians' decisions whether to admit to
      hospital patients with acute pyelonephritis, we conducted a multicentre,
      prospective, observational study in 12 emergency departments in France; 582
      consecutive patients were included. The reference standard for admission was
      defined by experts' advice combined with necessity of admission or death during
      the 28-day follow-up. Baseline CRP, PCT and ANP were measured and their accuracy
      in identifying the necessity of admission was analysed using area under curves
      (AUC) of receiver-operating characteristic (ROC) plots. According to the
      reference standard, 126 (22%) patients required admission. ANP (AUC 0.75, 95% CI
      0.69-0.80) and PCT (AUC 0.75, 95% CI 0.71-0.80) more accurately predicted this
      than did CRP (AUC 0.69, 95% CI 0.64-0.74). The positive and negative likelihood
      ratios for each biomarker remained clinically irrelevant whatever the threshold.
      Our results did not support the use of these markers to help physicians in
      deciding about admission of patients experiencing acute pyelonephritis in daily
      practice.

PMID- 19747217
TI  - Development of bacteraemia or fungaemia after removal of colonized central venous
      catheters in patients with negative concomitant blood cultures.
AB  - There are limited data on the clinical significance of positive central venous
      catheter (CVC) tip cultures associated with concomitant negative blood cultures
      performed at the time of CVC removal. A retrospective cohort study of all
      patients who yielded isolated positive CVC tip cultures was conducted in a
      tertiary-care hospital with 2200 beds during a 10-year period. All patients with
      isolated positive CVC tip cultures were observed for the development of
      subsequent bacteraemia or fungaemia between 2 and 28 days after CVC removal. An
      isolated positive CVC tip culture was defined as a case in which (i) a CVC tip
      culture yielded > or = 15 colonies using a semiquantitative culture method and
      (ii) at least two sets of blood samples revealed no organism at, or close to, the
      time of CVC removal (48 h before to 48 h after CVC removal). During the study
      period, 312 patients with isolated positive CVC cultures were enrolled. Eight
      (2.6%; 95% CI 1.2-5.1) of the 312 patients yielding isolated bacterial or fungal
      CVC tip cultures developed subsequent bloodstream infection (BSI) caused by the
      same species as that isolated from the tip culture (Staphylococcus aureus, 1:
      Enterococcus spp.; 2: Pseudomonas aeruginosa; and 3: Candida spp.). Among 125
      patients from whose CVC tips the above four organisms were grown, seven (12.3%)
      of 57 patients who did not receive appropriate antibiotic therapy within 48 h
      after CVC removal subsequently developed BSI, but only one (1.5%) of 68 patients
      who did receive appropriate therapy developed BSI (OR 0.11, p 0.02).

PMID- 19747218
TI  - CCL13 is a promising diagnostic marker for systemic sclerosis.
AB  - BACKGROUND: Previous studies suggest that CCL13 may have some role in the
      pathogenesis of systemic sclerosis (SSc). OBJECTIVES: To determine serum levels
      of CCL13 and its clinical associations in patients with SSc. METHODS: Serum CCL13
      levels were examined by enzyme-linked immunosorbent assay in 80 patients with
      SSc, 20 patients with systemic lupus erythematosus (SLE), 20 patients with
      dermatomyositis (DM), 29 patients with atopic dermatitis (AD) and 50 healthy
      individuals. RESULTS: Mean + or - SD serum CCL13 levels were elevated in patients
      with SSc (81.3 + or - 55.8 pg mL(-1)) compared with healthy controls (15.0 + or -
      9.9 pg mL(-1); P < 0.001) and patients with SLE (22.0 + or - 6.9 pg mL(-1); P <
      0.001), DM (24.4 + or - 36.1 pg mL(-1); P < 0.001) and AD (18.0 + or - 6.4 pg mL(
      1); P < 0.001). Among patients with SSc, there were no differences in serum CCL13
      levels between limited cutaneous SSc and diffuse cutaneous SSc. In a longitudinal
      study, CCL13 levels were generally unchanged during the follow-up. CONCLUSIONS:
      Serum CCL13 was specifically increased in patients with SSc, but not in patients
      with SLE, DM or AD or in healthy controls. CCL13 could be a promising serological
      marker for SSc.

PMID- 19747223
TI  - Myofibroblasts in the normal conjunctival surface.
AB  - PURPOSE: To investigate the occurrence of myofibroblasts (MFBs) in the normal
      conjunctival surface and to evaluate any anatomical and time-related variations.
      METHODS: MFBs were screened among healthy individuals (35 eyes) by collecting
      impression cytology (IC) samples from the bulbar conjunctiva. A cohort of
      volunteers (12 eyes) was followed for 1 year by taking two to five imprints every
      month. MFBs were identified by immunohistochemical localization of the MFB marker
      alpha-smooth-muscle actin (alpha-SMA). RESULTS: Using a filter imprint technique,
      MFBs were found consistently in 94% of samples from the conjunctival surface of
      participating individuals. The overall MFB levels, expressed as percentage of all
      cells on the filter, were highest in March-May [mean 4.1%, standard deviation
      (SD) +/- 1.5] and lowest in December-February (mean 1.2%, SD +/- 0.5). The
      difference was statistically significant [p < 0.0005, Friedman test, one-way
      repeated measures analysis of variance (anova)]. Moreover, there was a clear
      divergence of MFB density between the nasal, temporal, superior and inferior
      bulbar conjunctiva (mean 1.7%, 1.9%, 22% and 9.7%, respectively). CONCLUSION:
      MFBs, known as a cellular constituent of granulation tissue in wound healing,
      occur in the normal conjunctival surface, which is a novel finding. Our results
      also show that MFB level follows a seasonal variation pattern in a temperate
      climate, increasing in April-September and decreasing in October-March. This
      variation might reflect a degree of a transient or ongoing state of tissue repair
      after conjunctival trauma or stress caused by exposure to environmental factors.

PMID- 19747224
TI  - Valsalva-related retinal venous dilation caused by defaecation.

PMID- 19747230
TI  - Dysfunction of the unfolded protein response increases neurodegeneration in aged
      rat hippocampus following proteasome inhibition.
AB  - Dysfunctions of the ubiquitin proteasome system (UPS) have been proposed to be
      involved in the aetiology and/or progression of several age-related
      neurodegenerative disorders. However, the mechanisms linking proteasome
      dysfunction to cell degeneration are poorly understood. We examined in young and
      aged rat hippocampus the activation of the unfolded protein response (UPR) under
      cellular stress induced by proteasome inhibition. Lactacystin injection blocked
      proteasome activity in young and aged animals in a similar extent and increased
      the amount of ubiquitinated proteins. Young animals activated the three UPR arms,
      IRE1alpha, ATF6alpha and PERK, whereas aged rats failed to induce the IRE1alpha
      and ATF6alpha pathways. In consequence, aged animals did not induce the
      expression of pro-survival factors (chaperones, Bcl-XL and Bcl-2), displayed a
      more sustained expression of pro-apoptotic markers (CHOP, Bax, Bak and JKN), an
      increased caspase-3 processing. At the cellular level, proteasome inhibition
      induced neuronal damage in young and aged animals as assayed using Fluorojade-B
      staining. However, degenerating neurons were evident as soon as 24 h
      postinjection in aged rats, but it was delayed up to 3 days in young animals. Our
      findings show evidence supporting age-related dysfunctions in the UPR activation
      as a potential mechanism linking protein accumulation to cell degeneration. An
      imbalance between pro-survival and pro-apoptotic proteins, because of
      noncanonical activation of the UPR in aged rats, would increase the
      susceptibility to cell degeneration. These findings add a new molecular vision
      that might be relevant in the aetiology of several age-related neurodegenerative
      disorders.

PMID- 19747231
TI  - Mortality shifts in Caenorhabditis elegans: remembrance of conditions past.
AB  - The analysis of age-specific mortality can yield insights into how anti-aging
      interventions operate that cannot be matched by simple assessment of longevity.
      Mortality, as opposed to longevity, can be used to assess the effects of an anti
      aging intervention on a daily basis, rather than only after most animals have
      died. Various gerontogene mutations in Caenorhabditis elegans have been shown to
      increase longevity as much as tenfold and to decrease mortality at some ages even
      more. Environmental alterations, such as reduced food intake (dietary
      restriction) and lower temperature also result in reduced mortality soon after
      the intervention. Here, we ask how soon anti-aging interventions, applied during
      adult life, affect age-specific mortality in nematodes. Using maximum likelihood
      analysis, we estimated the Gompertz parameters after shifts of temperature, and
      of food concentration and maintenance conditions. In separate experiments, we
      altered expression of age-1 and daf-16, using RNAi. Using about 44 000 nematodes
      in total, to examine daily mortality, we find that for both types of
      environmental shift, mortality responded immediately in the first assessment,
      while RNAi-induced changes resulted in a slower response, perhaps due to delayed
      mechanics of RNAi action. However, under all conditions there is a permanent
      'memory' of past states, such that the initial mortality component [a] of the
      Gompertz equation [mu(x) = ae(bx)] bears a permanent 'imprint' of that earlier
      state. However, 'b' (the rate of mortality increase with age) is always specified
      by the current conditions.

PMID- 19747232
TI  - Methionine sulfoxide reductase A expression is regulated by the DAF-16/FOXO
      pathway in Caenorhabditis elegans.
AB  - The methionine sulfoxide reductase system has been implicated in aging and
      protection against oxidative stress. This conserved system reverses the oxidation
      of methionine residues within proteins. We analyzed one of the components of this
      system, the methionine sulfoxide reductase A gene, in Caenorhabditis elegans. We
      found that the msra-1 gene is expressed in most tissues, particularly in the
      intestine and the nervous system. Worms carrying a deletion of the msra-1 gene
      are more sensitive to oxidative stress, show chemotaxis and locomotory defects,
      and a 30% decrease in median survival. We established that msra-1 expression
      decreases during aging and is regulated by the DAF-16/FOXO3a transcription
      factor. The absence of this enzyme decreases median survival and affects
      oxidative stress resistance of long lived daf-2 worms. A similar effect of MSRA-1
      absence in wild-type and daf-2 (where most antioxidant enzymes are activated)
      backgrounds, suggests that the lack of this member of the methionine repair
      system cannot be compensated by the general antioxidant response. Moreover,
      FOXO3a directly activates the human MsrA promoter in a cell culture system,
      implying that this could be a conserved mechanism of MsrA regulation. Our results
      suggest that repair of oxidative damage in proteins influences the rate at which
      tissues age. This repair mechanism, rather than the general decreased of radical
      oxygen species levels, could be one of the main determinants of organisms'
      lifespan.

PMID- 19747233
TI  - The growth hormone receptor gene-disrupted mouse fails to respond to an
      intermittent fasting diet.
AB  - The interaction of longevity-conferring genes with longevity-conferring diets is
      poorly understood. The growth hormone receptor gene-disrupted (GHR-KO) mouse is
      long lived; and this longevity is not responsive to 30% caloric restriction, in
      contrast to wild-type animals from the same strain. To determine whether this may
      have been limited to a particular level of dietary restriction, we subjected GHR
      KO mice to a different dietary restriction regimen, an intermittent fasting diet.
      The intermittent fasting diet increased the survivorship and improved insulin
      sensitivity of normal males, but failed to affect either parameter in GHR-KO
      mice. From the results of two paradigms of dietary restriction, we postulate that
      GHR-KO mice would be resistant to any manner of dietary restriction; potentially
      due to their inability to further enhance insulin sensitivity. Insulin
      sensitivity may be a mechanism and/or a marker of the lifespan extending
      potential of an intervention.

PMID- 19747235
TI  - Is transcranial Doppler ultrasound undervalued for detection of intracranial
      internal carotid artery stenosis?

PMID- 19747234
TI  - Hot topics in aging research: protein translation, 2009.
AB  - In the last few years, links between regulation of mRNA translation and aging
      have been firmly established in invertebrate model organisms. This year, a
      possible relationship between mRNA translation and aging in mammals has been
      established with the report that rapamycin increases lifespan in mice. Other
      significant findings have connected translation control with other known
      longevity pathways and provided fodder for mechanistic hypotheses. Here, we
      summarize advances in this emerging field and raise questions for future studies.

PMID- 19747236
TI  - Coil embolization of intracranial dissecting vertebral artery aneurysms with
      subclavian steal.
AB  - Subclavian steal phenomenon occurs when cerebral blood flow is diverted to supply
      the arm. We report 3 patients with asymptomatic subclavian steal phenomenon with
      retrograde blood flow in the vertebral artery who presented with subarachnoid
      hemorrhage due to dissecting aneurysms of the involved vertebral artery. The
      association of subclavian steal phenomenon complicated by subarachnoid hemorrhage
      due to dissecting vertebral aneurysms has not been previously described.

PMID- 19747237
TI  - Isolated and reversible lesions of the corpus callosum: a distinct entity.
AB  - The Reversible Splenial Lesion Syndrome represents a distinct clinicoradiological
      syndrome, associated with several disorders, including infection, high altitude
      cerebral edema, antiepileptic drug withdrawal, and severe metabolic disturbances
      (hypoglycemia and hypernatremia). Clinical presentation is nonspecific, most
      frequently as an encephalopathy or encephalitis. Outcome is favorable in most
      patients unless there is a severe underlying disorder. Magnetic resonance imaging
      findings are restricted to the splenium and consist of a nonenhancing oval
      lesion, hyperintense on T2-weighted images, including FLAIR. Findings on
      diffusion-weighted imaging are consistent with cytotoxic edema except for high
      altitude cerebral edema, where vasogenic edema is present. Resolution after weeks
      or months is the rule.

PMID- 19747238
TI  - How to search and harvest the medical literature: let the citations come to you,
      and how to proceed when they do.
AB  - BACKGROUND: There is a virtual avalanche of medical information available to
      clinicians and researchers. The traditional 'search' can be substantially
      augmented by proactive 'harvesting.' AIMS: To describe how to search and harvest
      the medical literature. MATERIALS & METHODS: Survey of selected resources
      available on the internet. RESULTS: PubMed remains the backbone of the
      traditional literature search. The availability of automated delivery of
      electronic tables of contents ('eTOCs'), electronic feeds of targeted search
      results, and workflow tools allows relevant articles to find the reader.
      Electronic storage and retrieval tools make it possible to manage this
      information and make day-to-day clinical and research activities more efficient.
      DISCUSSION: Searching and harvesting the medical literature is made easier with
      the advent of the internet and email. In addition, there are internet resources
      that screen and filter potential articles of interest. Managing one's electronic
      library of PDF documents requires attention to appropriately naming files and the
      use of indexing programs. CONCLUSION: In addition to readers searching for
      relevant citations, these citations themselves can be searching for readers.
      Clinicians and researchers can take advantage of this and efficiently harvest the
      medical literature with a modest investment of time.

PMID- 19747240
TI  - Sunscreens: expectation and realization.
AB  - BACKGROUND: The technical performance of sunscreens has improved dramatically
      over the past 20 years, so have we now succeeded in delivering protection that
      meets consumers' expectations? METHODS: From a public health perspective, the
      desire to prevent sunburn and protect against skin cancer are the two major
      drivers for using sunscreen. This review examines how well consumers can expect
      to realize these expectations. RESULTS: Sunscreens are used regularly by a
      minority of people, even during recreational summer exposure. The failure of
      sunscreen to prevent sunburn is almost always due to the way that sunscreens are
      applied rather than technical failure of the product. The mismatch between the
      labelled protection (sun protection factor) and that delivered in practice is a
      contributory factor to this 'failure'. Sunscreens have been shown to be effective
      in reducing the incidence of squamous cell cancer and with promising benefits for
      basal cell cancer. However, the evidence that they are effective in melanoma
      remains lacking. CONCLUSION: The formulation and extinction of sunscreens have
      undoubtedly improved over recent years. Yet the notion that sunscreens provide
      unequivocal protection against the deleterious effects of sun exposure by
      everyone who uses them remains elusive.

PMID- 19747241
TI  - Topical 8-methoxypsoralen increases the efficacy of narrowband ultraviolet B in
      psoriasis.
AB  - BACKGROUND: A combination of oral psoralen with narrowband ultraviolet B (UVB),
      defined as 'psoralen-narrowband UVB', was shown to have a superior efficacy than
      UVB alone and even a comparable efficacy to psoralen and ultraviolet A in
      psoriasis. OBJECTIVE: To find out whether topical psoralen-narrowband UVB
      provides any additional benefit to narrowband UVB alone in psoriasis. METHODS:
      Nineteen patients with plaque psoriasis were included. Phototherapy was given
      three times per week. Two symmetrical lesions were selected as target lesions. In
      the first 12 sessions of phototherapy, the target lesion on one side was treated
      with 1% 8-methoxypsoralen (MOP) gel 30 min before UVB radiation whereas the
      target lesion on the other side served as a control. Target lesion scores were
      assessed at baseline, third, sixth, ninth and 12th sessions. Side effects were
      recorded. RESULTS: Sixteen patients completed the study. Target lesion scores
      decreased significantly on both sides (P<0.0001). The mean percentage of
      decreases was greater on the 8-MOP-applied sides compared with the control sides
      for all assessments, but the difference was statistically significant only at the
      ninth session (37.7% vs. 58.6%, P=0.043). Pigmentation was frequently seen in 8
      MOP gel-applied lesions. CONCLUSION: Topical 8-MOP gel plus narrowband UVB has
      greater efficacy than narrowband UVB alone in psoriasis.

PMID- 19747242
TI  - Application of sunscreen preparations: a need to change the regulations.
AB  - BACKGROUND/PURPOSE: To achieve photoprotection indicated on the package of
      sunscreen products they should be used appropriately. As previously published
      data documented that people usually applied much less than the recommended dose,
      the current study was undertaken to assess whether a detailed instruction can
      improve the use of sunscreens. METHODS: A total of 105 volunteers were asked to
      apply sunscreen to the whole skin surface in the same way that they would do it
      before sun exposure. A subgroup of patients (n=53) were precisely instructed
      about the proper usage of sunscreens and compared with uninstructed subjects
      (n=52). Each tube containing the tested product was weighed before and after
      application to determine the quantity of the substance, that was used, and to
      compare it with the recommended dose. RESULTS: Instructed subjects used
      significantly more sunscreens (mean 8.6 +/- 4.1 g/m(2)) compared with
      uninstructed controls (mean 6.8 +/- 3.9 g/m(2), P=0.03). However, both groups
      used much less of sunscreens than was the recommended amount (i.e. 43.0% and
      34.1% of the recommended dose, respectively). CONCLUSION: Current regulations
      about the sunscreen use are inadequate when compared with clinical practice and
      better standards of photoprotection should be elaborated in the future.

PMID- 19747243
TI  - A study of the way in which dermatologists and photosensitive patients apply
      sunscreen in China.
AB  - OBJECTIVE: To study sunscreen product application by dermatologists and
      photosensitive patients in China for drawing up proper directions for most
      efficient use of sunscreen. METHODS: Thirty-nine dermatologists and 41
      photosensitive patients were enrolled in this study. They were asked to apply the
      cream in the same way they apply sunscreen products. The mimicking cream
      contained dipyridamole, which is fluorescent under Wood's light (WL). Cream
      distribution on skin and applied amount were visually assessed under WL using a
      grading scale. RESULTS: Based on results from mimicking cream use, sunscreen
      application by both dermatologists and photosensitive patients was shown to be
      inadequate, i.e. wrongly done with the palm of the hand, unevenly distributed, an
      insufficient amount applied, and/or sensitive areas left uncovered. The ears,
      neck, and dorsum of the hands were most often left unprotected. CONCLUSION:
      Inadequate sunscreen application was found to be a common failing in both
      dermatologists and photosensitive patients. Suitable application was only
      provided on central, prominent areas, with a sharply decreasing gradient of
      product and low application toward lateral regions of the body as a result.
      Continuous education and further training programs are urgently needed to ensure
      the correct application of sunscreen and to provide effective sun protection.

PMID- 19747244
TI  - Mitigation of acute ultraviolet B radiation-mediated damages by baicalin in mouse
      skin.
AB  - BACKGROUND: Solar ultraviolet (UV) irradiation, in particular UVB with a
      wavelength range between 290 and 320 nm, induces different hazardous effects on
      the skin, including sunburn, photoaging and cancer. Protection against sun
      induced damage is therefore a highly desirable goal. Chemoprevention is being
      investigated as a potential approach for the management of UV damages including
      skin cancer. AIM: In this study, to determine the relevance of our in vitro
      findings to in vivo situations, we assessed the effects of baicalin on UVB
      mediated damages in mice skin. METHODS: Balb/C hairless mice were topically
      pretreated (24 h before UVB) or post-treated (5 min after UVB) with baicalin (1
      mg/cm(2) skin area/mouse/100 microl acetone) and were exposed to UVB 24 h later
      (180 mJ/cm(2)). The animals were sacrificed 1 and 24 h after the UVB exposure.
      Skin edema, histopathology changes, hydrogen peroxide (H2O2) and cyclobutane
      pyrimidine dimers (CPDs)-positive cells were assessed to determine the UVB
      induced photodamage. RESULTS: Our data demonstrated that a topical application of
      baicalin, either as a pretreatment or as a post-treatment, resulted in a
      significant decrease in UVB mediated increases in skin edema, skin hyperplasia
      and infiltration of leukocytes. Further, baicalin treatments (pre and post) also
      resulted in a significant decrease in UVB mediated (1) generation of H2O2 and (2)
      formation of DNA photolesions: CPDs. CONCLUSION: Based on these data, we suggest
      that baicalin could be developed as an agent for the management of conditions
      elicited by UV exposure including skin cancer.

PMID- 19747245
TI  - Antitumor effect of photodynamic therapy in mice using direct application of
      Photofrin dissolved in lidocaine jelly.
AB  - BACKGROUND/PURPOSE: Photodynamic therapy (PDT) is a non-invasive cancer therapy
      that has a strong antitumor effect with intravenous administration of Photofrin.
      However, Photofrin causes light hypersensitivity that impairs the quality of life
      (QOL) of patients, and thus an improved method of administration is needed. Here,
      we report the antitumor effect of local administration of Photofrin in
      combination with a vasodilator, lidocaine hydrochloride. METHOD: The antitumor
      effect was investigated in nude mice transplanted with HeLa cells. An incision
      was made near the tumor and Photofrin dissolved in lidocaine jelly was applied
      directly to the tumor. The tumor was irradiated at 100 J/cm(2) with a yttrium
      aluminum garnet (YAG)-dye laser (630 nm) at 2 h after the direct application and
      the tumor volume was measured for 30 days after PDT to investigate the antitumor
      effect. In some mice, the tumor was excised 24 h after PDT and the depth of
      necrosis was measured in the excised specimen. RESULT: The tumor was mostly
      necrotized by PDT following direct application of 10 mg/ml Photofrin dissolved in
      lidocaine jelly and the effect was greater than with direct application of
      Photofrin alone. The increase in tumor volume observed in control mice was
      significantly inhibited in mice that received PDT after direct application of
      Photofrin in lidocaine jelly. CONCLUSION: PDT using direct application of
      Photofrin in lidocaine jelly has a strong antitumor effect in mice and this
      approach may avoid the adverse effects of systemic Photofrin administration.

PMID- 19747246
TI  - Reversal of ultraviolet B-induced immunosuppression by inhibition of the
      extracellular signal-regulated mitogen-activated protein kinase.
AB  - OBJECTIVE: Topical treatment of the specific inhibitor PD98059 (PD) for
      extracellular signal-regulated kinase (ERK)1/2 combined with ultraviolet B (UVB)
      exposure in an in vivo study was proposed to confirm the effectiveness of ERK1/2
      involved in UVB-induced immunosuppression that was reversed by PD. METHODS: Based
      on the mouse model of local UVB-induced immunosuppression [UVB exposure, followed
      by sensitization with dinitrofluorobenzene (DNFB) on the abdomen skin before
      challenge on the ear site], the PD was applied on the abdomen-irradiated area 1
      h, immediately before and 6 h after UVB exposure, respectively. The baseline of
      ear thickness was measured and remeasured 24 h after the challenge of DNFB for
      evaluation of ear-swelling response. Histopathologically, the ear biopsies were
      taken for hematoxylin and eosin staining. RESULTS: Mice that received PD post
      irradiation treatment showed a statistically significant contact hypersensitivity
      compared with the UVB-irradiated mice (P<0.05), and paralleled with the biopsy
      showing a thickened epidermis with lymphocyte infiltration. Thus, the PD had
      abrogated the UV-induced local suppression of contact hypersensitivity.
      CONCLUSION: The ERK1/2 mitogen-activated protein kinase (MAPK) pathway plays an
      important role in the local UVB-induced immunosuppression, and its specific
      inhibitor PD can arrest its function, resulting in protection against UVB-induced
      immunosuppression in the present in vivo study.

PMID- 19747247
TI  - Phototoxic reactions in healthy volunteers following photodynamic therapy with
      methylaminolevulinate cream or with cream containing 5-aminolevulinic acid: a
      phase II, randomized study.
AB  - BACKGROUND: Photodynamic therapy (PDT) is the selective destruction of abnormal
      cells through activation of a photosensitizer in the presence of oxygen. Local
      phototoxic reactions and pain are the most common limiting side effects. PURPOSE:
      The primary objective was to compare the local phototoxic response following PDT
      with methylaminolevulinate (MAL) and 5-aminolevulinic acid (ALA). The secondary
      objectives were to compare the two treatments regarding pain, detection of
      substance P, change in fluorescence intensity from before to 5 h after cream
      application and adverse events not related to local phototoxicity. METHODS:
      Thirty-four healthy volunteers were treated by PDT using MAL 160 mg/g cream and
      ALA cream 20% randomly assigned to treatment areas on the inside of each upper
      arm. A composite score of local phototoxic events (erythema, edema,
      hyperpigmentation) was calculated. RESULTS: The area under the curve (AUC)
      analysis of composite scores showed a significantly higher AUC for ALA-PDT (P <
      or =0.0001). ALA- and MAL-PDT showed equivalent local side-effect frequencies,
      except for a higher frequency of hyperpigmentation after 28 d using ALA-PDT
      (P=0.006). CONCLUSION: MAL- and ALA-PDT are nearly equivalent regarding
      individual side-effect frequencies, but MAL-PDT has a more favorable
      phototoxicity pattern as seen by AUC analysis and the lower frequency of long
      lasting hyperpigmentation.

PMID- 19747248
TI  - Successful treatment of cutaneous sarcoid by photodynamic therapy with minimal
      discomfort using a fractionated dosing regime.
AB  - We report the case of a 42-year-old lady with an 8-year history of a persistent
      tumid plaque on her forehead. Investigations and presentation were consistent
      with cutaneous sarcoid with no systemic involvement. Multiple topical and oral
      treatments had been ineffective. She received seven sessions of 5-aminolaevulinic
      acid photodynamic therapy (PDT) over the course of 16 months. Each treatment was
      delivered in discontinuous and fractionated time intervals. Improvement was seen
      after the first treatment and continued with subsequent treatments. She found the
      treatment almost painless and was pleased with the cosmetic outcome. We conclude
      that PDT is a useful therapy in the treatment of facial cutaneous sarcoid.
      Fractionated exposure may allow the treatment to be less painful and therefore
      better tolerated.

PMID- 19747249
TI  - Fractional 1320 nm Nd : YAG laser in the treatment of acne vulgaris: a pilot
      study.
AB  - Thirty-five patients with moderate to severe acne were treated with a fractional
      1320 nm neodymium : yttrium aluminum garnet (Nd : YAG) laser. These patients
      received six treatment sessions at a 2-week interval. Inflammatory and non
      inflammatory lesions were counted before and after treatment. Fractional 1320 nm
      Nd : YAG laser therapy was well tolerated, resulting in the reduction of
      inflammatory lesions by 57% (P<0.05) and the reduction of non-inflammatory
      lesions by 35% (P<0.05). A significant reduction in the skin sebum level by 30%
      (P<0.05) was also noted after treatment.

PMID- 19747250
TI  - Photodynamic therapy using direct-current pulsed iontophoresis for 5
      aminolevulinic acid application.
AB  - In photodynamic therapy (PDT) for skin cancer, 5-aminolevulinic acid (ALA) is
      applied topically to the affected area to be absorbed percutaneously through
      passive diffusion, and typically requires 4-6 h before performing PDT. In this
      study, we attempted to reduce the absorption period in PDT by ionizing ALA using
      direct-current pulsed iontophoresis to treat actinic keratosis (AK). Twenty
      percent ALA solution was applied to AK lesions of five patients using direct
      current pulsed iontophoresis. ALA-PDT was repeated three times with a total
      irradiation of 150 J/cm(2) (50 J/cm(2) per irradiation, weekly). One week after
      the last PDT, therapeutic results were assessed by skin biopsy. In all subjects,
      protoporphyrin IX (PpIX) production was confirmed after iontophoresis, and its
      production levels were comparable to the conventional occlusive dressing
      technique (ODT). Skin biopsies from the treated lesion showed the disappearance
      of tumour cells. These results indicated that direct-current pulsed iontophoresis
      for applying ALA before PDT is useful to treat AK.

PMID- 19747251
TI  - Successful treatment of large venous malformation with dual wavelength 595 and
      1064 nm system.
AB  - Venous malformations (VMs) are congenital soft, compressible, non-pulsatile blue
      purple masses. VMs present a therapeutic challenge. They can be treated with
      surgery or sclerotherapy as well as with several lasers. We report the successful
      treatment of two patients with large VMs with combined sequential application of
      595 nm pulsed dye laser and 1064 nm Nd:YAG wavelengths. At the end of the
      treatment course, total volume reduction was observed in both. All sessions were
      well tolerated without anesthesia. In our patients, using this sequential laser
      device achieved an almost complete clearance of the VM with no scarring.

PMID- 19747252
TI  - Editorial: rating research performance.

PMID- 19747253
TI  - A review of the literature on the impact of renal cancer therapy on quality of
      life.
AB  - AIM: To explore the impact of renal cancer treatment on patients' quality of
      life. BACKGROUND: Renal cancer accounts for 95,000 deaths worldwide and its
      incidence rate is rising. At present there are several therapeutic approaches to
      the treatment of renal cancer, ranging through surgery, immunological therapies
      and vaccine treatment. Each of these therapies may have a substantial effect upon
      patients' quality of life. However, a systematic appraisal of the empirical
      evidence about treatment impact is lacking. DESIGN: Literature review. METHODS: A
      structured review of the empirical literature on the impact of renal cancer
      treatment upon quality of life was undertaken. Literature was appraised and
      themed according to the treatment modalities included in the study. RESULTS: From
      873 papers initially identified 52 were retrieved for detailed scrutiny resulting
      in a final 16 papers being included in the review. CONCLUSIONS: This review
      discusses the complex effect of renal cancer upon a patient's quality of life as
      treatment modalities change. The need for nursing education and awareness of
      these issues is therefore highlighted to maximise patient care. RELEVANCE TO
      CLINICAL PRACTICE: Understanding the impact of treatment for renal cancer enables
      nurses to empathise more significantly with patients and also act as mediators in
      regard to treatment choice and treatment cessation. It also enables nurses to
      inform and educate renal cancer patients prior to making treatment choices.

PMID- 19747254
TI  - Self-care among persons using advanced medical technology at home.
AB  - AIM: This study aimed to describe lived experiences of self-care among persons
      using advanced medical technology at home. BACKGROUND: An increased number of
      people are performing self-care while using different sorts of advanced medical
      technology at home. Knowledge of different patient groups' lived experiences of
      this situation may be useful for nurses and other caregivers in educating and
      supporting these patients. DESIGN: A qualitative design was used. METHODS:
      Suitable patients in western Sweden were informed by their nurses and invited to
      participate. Ten people, who performed self-care at home, either while using long
      term oxygen therapy from a ventilator or oxygen cylinder, or while performing
      peritoneal or haemodialysis, were interviewed. The interviews were analysed using
      a descriptive phenomenological methodology. RESULTS: Prerequisites for self-care
      when using advanced medical technology at home were: support from professional
      caregivers and significant others; cognitive capacity; and a positive attitude to
      life. This type of self-care contains steps for living healthy, for planning and
      for adjusting technology. It involves a process of learning and feelings both of
      being tied up and of feeling free. Additionally, it has influences on the home
      environment. CONCLUSION: Self-care in this context can be described on a generic
      level. Self-care is more than mastering the technology; it also means dealing
      with daily life activities for healthy living, planning for the use of the
      equipment and activities, having knowledge about bodily signs of good and ill
      health, and adjusting treatment according to the circumstances. RELEVANCE TO
      CLINICAL PRACTICE: Self-care in this context involves a learning process with
      education and continuing access to support from professional caregivers. With
      knowledge and support, patients are able to assume substantial responsibility for
      self-care. Needs for design improvements of medical technology for use at home
      are raised.

PMID- 19747255
TI  - Therapeutic relationships in day surgery: a grounded theory study.
AB  - AIM: To explore patients' experiences of day surgery. BACKGROUND: Therapeutic
      relationships are considered to be a core dimension of nursing care. However, in
      modern health care with short hospital stays the formation of these relationships
      may be impeded. A major theme to emerge from this study was the development of
      therapeutic relationships in the day surgery setting. DESIGN: The Glaserian
      method of Grounded Theory was used. METHODOLOGY: Semi-structured interviews with
      145 patients took place from 2004-2006 in two-day surgery units in the UK.
      Analysis involved transcriptions of interviews and memos. Lists of key words and
      phrases were made and constantly compared until core categories emerged. RESULTS:
      Patients spoke highly of the relationships they developed with nurses during
      their stay in the day surgery unit. Analysis of the data revealed the core
      category of therapeutic relationships and four sub core categories: 'presence',
      'extra special', 'befriending' and 'comfort-giving.' CONCLUSION: This paper adds
      to the growing body of literature which demonstrates that therapeutic
      relationships can be developed within the short stay arena of health care:
      routine interactions which may not be considered to be significant by nurses may
      be of importance to patients. The patients in this study felt supported,
      comforted and befriended by day surgery nurses. However a minority of patients
      were disappointed with the nursing staffs' lack of interpersonal responses to
      their needs. RELEVANCE TO CLINICAL PRACTICE: Anecdotal evidence suggests that
      personnel working within day surgery are not always aware of their therapeutic
      potential. Therefore raising awareness of this through research generated from
      patients' experiences might encourage nurses to further realise their
      capabilities in this fundamental area of nursing.

PMID- 19747256
TI  - Instructive messages from Chinese nurses' stories of caring for SARS patients.
AB  - AIM: To identify instructive messages to guide nursing practice in future
      epidemics by examining the stories of Chinese nurses who cared for severe acute
      respiratory syndrome (SARS) patients. BACKGROUND: Mainland China had three
      outbreaks of SARS between November 2002-May 2004 and suffered the greatest impact
      on morbidity and mortality worldwide. Most of the nursing-related literature
      about SARS has been reported from other countries. Researchers expect that global
      infections, like SARS, will persist and escalate in the future. It is important
      to access the guidance from nurses who cared for SARS patients in China and to
      uncover instructive messages which can be useful when facing global infections in
      the future. DESIGN: Descriptive exploratory qualitative study of six Chinese
      nurses. METHODS: Data were collected in 2003, within the three months following
      the nurses' quarantine necessitated by caring for SARS patients. Conventional
      content analysis was done using a cyberspace method of data analysis, where the
      geographically distant researchers conducted most phases of analysis through
      email communication. RESULTS: Chinese nurses faced personal challenge, focused on
      the essence of care and experienced self-growth while caring for SARS patients.
      They cited structured support, meaningful disease-related information and
      sensitivity to the importance of a collaborative spirit as factors which enabled
      their caring nursing practice. CONCLUSIONS: These instructive messages come from
      China, where the SARS epidemic inflicted an unparalleled health impact. The
      messages give voice to the Chinese nursing experience and when synthesised with
      reports from other international nurses, they enable specific direction to
      enhance potential for a well-prepared nursing workforce and quality patient care
      in future epidemics. RELEVANCE TO CLINICAL PRACTICE: The preparation of a
      knowledgeable, cared-for nursing workforce promises optimal outcomes with the
      emergence of the next global infection.

PMID- 19747257
TI  - Commentary on Pollard K (2009) Student engagement in interprofessional working in
      practice placement settings. Journal of Clinical Nursing 18, 2846-2856.

PMID- 19747258
TI  - Commentary on Levett-Jones T & Lathlean J (2009) The ascent to competence
      conceptual framework: an outcome of a study of belongingness. Journal of Clinical
      Nursing 18, 2870-2879.

PMID- 19747260
TI  - Response to Harbison J (2009) Commentary on Taylor J, Baldwin N & Spencer N
      (2008) Predicting child abuse and neglect: ethical, theoretical and
      methodological challenges. Journal of Clinical Nursing 17, 1193-1200 in Journal
      of Clinical Nursing 18, 621-622.

PMID- 19747262
TI  - Regulatory feedback loop between NF-kappaB and MCP-1-induced protein 1 RNase.
AB  - A novel gene ZC3H12A, encoding MCP-1-induced protein 1 (MCPIP), was recently
      identified in human peripheral blood monocytes treated with monocyte chemotactic
      protein 1 (MCP-1) and in human monocyte-derived macrophages stimulated with
      interleukin (IL)-1beta. These experiments revealed that the gene undergoes rapid
      and potent transcription induction upon stimulation with proinflammatory
      molecules, such as MCP-1, IL-1beta, tumour necrosis factor alpha and
      lipopolysaccharide. Here we show that the induction of ZC3H12A by IL-1beta is
      predominantly NF-kappaB-dependent because inhibition of this signalling pathway
      results in the impairment of ZC3H12A transcription activation. Our results
      indicate the presence of an IL-1beta-responding region within the second intron
      of the ZC3H12A gene, which contains four functional NF-kappaB-binding sites.
      Therefore, we propose that this transcription enhancer transduces a ZC3H12A
      transcription-inducing signal after IL-1beta stimulation. Recent reports suggest
      that MCPIP acts as a negative regulator of inflammatory processes because it is
      engaged in the degradation of transcripts coding for certain proinflammatory
      cytokines. Our observations provide evidence for a novel negative feedback loop
      in the activation of NF-kappaB and point to potential significance of MCPIP in
      the treatment of various pathological states, such as diabetes or cancer that
      involve disturbances in the functioning of the NF-kappaB system.

PMID- 19747263
TI  - Maternity leave benefits in the United States: today's economic climate
      underlines deficiencies.

PMID- 19747264
TI  - Outcomes associated with planned home and planned hospital births in low-risk
      women attended by midwives in Ontario, Canada, 2003-2006: a retrospective cohort
      study.
AB  - BACKGROUND: Midwives in Ontario, Canada, provide care in the home and hospital
      and are required to submit data for all births to the Ontario Ministry of Health
      database. The purpose of this study was to compare maternal and
      perinatal/neonatal mortality and morbidity and intrapartum intervention rates for
      women attended by Ontario midwives who planned a home birth compared with similar
      low-risk women who planned a hospital birth between 2003 and 2006. METHODS: The
      database provided outcomes for all women planning a home birth at the onset of
      labor (n = 6,692) and for a cohort, stratified by parity, of similar low-risk
      women planning a hospital birth. RESULTS: The rate of perinatal and neonatal
      mortality was very low (1/1,000) for both groups, and no difference was shown
      between groups in perinatal and neonatal mortality or serious morbidity (2.4% vs
      2.8%; relative risk [RR], 95% confidence intervals [CI]: 0.84 [0.68-1.03]). No
      maternal deaths were reported. All measures of serious maternal morbidity were
      lower in the planned home birth group as were rates for all interventions
      including cesarean section (5.2% vs 8.1%; RR [95% CI]: 0.64 [0.56, 0.73]).
      Nulliparas were less likely to deliver at home, and had higher rates of ambulance
      transport from home to hospital than multiparas planning home birth and had rates
      of intervention and outcomes similar to, or lower than, nulliparas planning
      hospital births. CONCLUSIONS: Midwives who were integrated into the health care
      system with good access to emergency services, consultation, and transfer of care
      provided care resulting in favorable outcomes for women planning both home or
      hospital births.

PMID- 19747265
TI  - Childhood abuse and common complaints in pregnancy.
AB  - BACKGROUND: Childhood abuse affects adult health. The objective of this study was
      to examine the prevalence of emotional, physical, and sexual childhood abuse
      within a large Norwegian cohort of pregnant women and its association with common
      complaints in pregnancy. METHODS: This study is based on the Norwegian Mother and
      Child Cohort Study (MoBa) conducted by the Norwegian Institute of Public Health.
      Regression analyses were used to examine associations of childhood abuse and 16
      common complaints in pregnancy. RESULTS: Eighteen percent (10,363/55,776) of the
      women reported some type of childhood abuse. Of all women, 3,870 (6.9%) reported
      sexual abuse, 3,075 (5.5%) physical abuse, and 7,619 (13.6%) emotional abuse as a
      child. Of those reporting childhood abuse, 31 percent reported two or more types
      of abuse. All 16 common complaints in pregnancy were associated with reported
      childhood abuse. Women reporting three types of childhood abuse reported 5.4
      common complaints in pregnancy (mean) compared with 3.7 for women without
      childhood abuse (p < 0.001). Women reporting childhood abuse are more likely to
      report seven or more common complaints in pregnancy: adjusted odds ratio (AOR)
      1.7 (95% CI 1.6-1.9) for emotional abuse; AOR 2.5 (95% CI 2.0-3.1) for combined
      physical and sexual abuse; and AOR 3.5 (95% CI 3.0-4.0) for all three kinds of
      abuse. Sociodemographic characteristics and other risk factors did not explain
      this graded association. CONCLUSIONS: Abuse in childhood is associated with
      increased reporting of common complaints of pregnancy. Clinicians should consider
      the possible role of childhood abuse when treating women with many common
      complaints in pregnancy.

PMID- 19747266
TI  - Exercise during pregnancy and cesarean delivery: North Carolina PRAMS, 2004-2005.
AB  - BACKGROUND: The current rate of cesarean delivery in the United States is 31
      percent. Previous studies have suggested that exercise during pregnancy may be
      associated with a lower risk of cesarean delivery, but sample sizes were small
      and methods often inadequate. This study examined whether or not an association
      exists between prenatal exercise and delivery mode using data from the 2004 and
      2005 North Carolina Pregnancy Risk Assessment Monitoring System (PRAMS) survey.
      METHODS: PRAMS postpartum questionnaire responses about frequency of exercise
      during the last 3 months of pregnancy for 1,955 women without a prior cesarean
      delivery were linked to birth certificates. RESULTS: Among 1,342 women delivering
      at term, exercise was not associated with delivery mode in this data set:
      compared with women exercising less than once a week, neither women exercising
      one to four times per week nor those exercising five times or more per week had
      an altered risk of cesarean (risk ratio [RR] [95% confidence limit] [CL] 0.89
      [0.69-1.15], 1.04 [0.66-1.64], respectively, adjusted for parity, gestational
      age, hypertension). Among 613 women delivering preterm, the results were also not
      statistically significant, but a compelling trend toward a protective effect
      could be seen (RR [95% CL] 0.65 [0.38-1.13], 0.62 [0.29-1.33]). CONCLUSIONS:
      Maternal self-reported frequency of exercise during pregnancy was not associated
      with a reduced risk of cesarean delivery. Larger studies with better exposure
      ascertainment may provide a more definitive answer.

PMID- 19747267
TI  - Estimating the rate of cesarean section by maternal request: anonymous survey of
      obstetricians in Australia.
AB  - BACKGROUND: The rate of cesarean section in Australia now exceeds 30 percent, and
      evidence from population studies indicates that maternal requests for elective
      cesarean delivery might make an important contribution. The objective of this
      study was to explore the rate of such deliveries in Australia, in the absence of
      a formal investigation. METHODS: An anonymous survey was sent to all 1,239
      specialist obstetricians and 317 obstetric specialty trainees in Australia.
      Specialists were asked the number of elective cesarean deliveries they performed
      in 2006 that satisfied the National Institutes of Health definition of maternal
      request cesarean delivery. Trainees were asked whether they intended to agree to
      maternal requests for cesarean section in their future specialist practice.
      RESULTS: The response rate from specialists was 98.6 percent, and from trainees
      was 81 percent. To account for possibility of multiple submissions, we performed
      two analyses: one using all responses, the other after removing 297 surveys in
      the second mail-out that were identical to surveys received from the first mail
      out (n = 735). Proportions were similar in both groups. We estimated that between
      8,553 and 12,434 maternal request cesarean sections were performed in Australia
      in 2006, representing at least 17 percent of all elective cesarean sections, and
      slightly more than 3 percent of all births. CONCLUSION: Maternal request is an
      important contributor to cesarean section rates in Australia.

PMID- 19747268
TI  - Primigravid women's views of being approached to participate in a hypothetical
      term cephalic trial of planned vaginal birth versus planned cesarean birth.
AB  - BACKGROUND: Several papers have called for a trial of planned cesarean section
      versus planned vaginal birth for low-risk women-a recommendation that is fiercely
      debated. Although proponents of a trial have voiced their support, evidence
      suggests that in the United Kingdom few midwives and obstetricians believe such a
      trial to be feasible, and no studies reporting women's views on the prospect of
      such a trial have been published. The purpose of this study is to explore women's
      views of participation in a trial of planned cesarean birth versus planned
      vaginal birth. METHODS: A qualitative study was conducted using in-depth
      interviews in a large maternity hospital in the United Kingdom. Sixty-four women
      were interviewed 12 months after giving birth. Women were asked "How do you think
      you would have felt if you had been approached to take part in such a trial
      during your first pregnancy?" Data were analyzed thematically. RESULTS: Only 3 of
      the 64 women stated that they would have participated in a trial of planned
      vaginal birth versus planned cesarean section, had they been asked. However, five
      other women said that they would have consented to participate if they had been
      asked during pregnancy, but with hindsight, would have regretted that decision.
      The remainder of women would not have participated, unless a preference arm was
      offered. Three main themes were identified: "feeling cheated," "let nature take
      its course," and "just another trauma that you don't need." CONCLUSIONS: Few
      women supported a trial and most suggested that it was intuitively wrong. Given
      the strong views voiced by women, it is unlikely that a trial of planned vaginal
      delivery versus planned cesarean delivery would be feasible.

PMID- 19747269
TI  - Women's experiences of participating in the Magpie Trial: a postal survey in the
      United Kingdom.
AB  - BACKGROUND: The Magpie Trial compared magnesium sulfate with placebo for women
      with preeclampsia. The objective of this study was to explore women's views and
      experiences of participating in the Magpie Trial in the United Kingdom. METHODS:
      Postal questionnaires were sent to 771 women participants in the Magpie Trial to
      assess long-term health of UK women and children. The questionnaire included
      three questions exploring women's experience of participating in the trial: (a)
      If time suddenly went backward, and you had to do it all over again, would you
      agree to participate in the Magpie Trial? (b) Please tell us if there was
      anything about the Magpie Trial that you think could have been done better; and
      (c) Please tell us if there was anything about the Magpie Trial, or your
      experience of joining the trial, that you think was particularly good. RESULTS:
      Overall, 619 of the 771 women who were sent questionnaires returned them. In
      response to the three questions: (a) 58 percent (356) of women responded
      "definitely yes," 27 percent (169) "probably yes," 4 percent (23) "probably no,"
      5 percent (33) "definitely no," and 5 percent (34) "not sure." No clear evidence
      was shown of a relationship with allocated treatment, although women who
      responded "probably or definitely no" were more likely to have had side effects
      from trial treatment. (b) Although 44 percent of women stated that nothing could
      have been done better, free text suggestions related to content of recruitment
      information, and its timing, and wanting to know treatment allocation and trial
      results. c) Women were generally extremely positive about being followed up and
      receiving trial results. CONCLUSIONS: Women were largely positive about
      participation in the trial and its follow-up, but still reported ways they
      believed the study could have been improved, such as more information, given
      earlier, which also has implications for clinical care.

PMID- 19747270
TI  - "Universal Precautions": perinatal touch and examination after childhood sexual
      abuse.
AB  - BACKGROUND: Childhood sexual abuse is a common experience of Australian women
      with 1 woman in 3 reporting unwanted sexual activity, and 1 in 10 reporting
      attempted or penetrative sexual abuse before 16 years of age. The objective of
      this study was to explore women's responses to perinatal professional touch and
      examination of themselves and their babies. METHODS: Eighteen women were
      interviewed using an in-depth semistructured qualitative method. Interviews were
      recorded and transcribed. The interviews were coded and thematically analyzed,
      using NVivo to assist with data management. To ensure rigor, four initial
      interviews were coded by a second researcher and discrepancies resolved. RESULTS:
      Two key themes were identified by childhood sexual abuse survivors as important
      in improving service provision: safety issues for survivors and their babies in
      the clinical encounter and ways of making service provision safer. CONCLUSIONS:
      Childhood sexual abuse survivors experienced pain, dissociation, fear, blame,
      helplessness, and guilt in their encounters with health care practitioners. These
      experiences led to the development of a set of "Universal Precautions" for
      perinatal professionals responding to women and their children.

PMID- 19747271
TI  - Women's use of complementary and alternative medicine during pregnancy: a
      critical review of the literature.
AB  - BACKGROUND: The use of complementary and alternative medicine has attracted much
      attention and debate in recent years. The objective of this critical review is to
      examine the evidence base on use of complementary products and therapies during
      pregnancy. It examines an important but neglected issue in maternity care.
      METHODS: A database search was conducted in MEDLINE, CINAHL, AMED, and Maternity
      and Infant Care. A total of 24 papers published between 1999 and 2008 met the
      selection criteria and were included in the review. RESULTS: Findings of these 24
      papers were extracted and reported under four themes: "user prevalence and
      profile,""motivation and condition of use,""perception and self-reported
      evaluation," and "referral and information sources." CONCLUSIONS: This review
      highlights four research gaps in the literature, a lack of: large representative
      samples; in-depth understanding of user experiences and risk perceptions;
      research comparing consumption patterns across cultures and over time; and work
      exploring the nature of the therapeutic encounter with complementary
      practitioners in this area of women's health care.

PMID- 19747273
TI  - Putting mothers and babies at risk: promoting the elusive "cesarean delivery on
      maternal request".

PMID- 19747272
TI  - Does acupuncture have a place as an adjunct treatment during pregnancy? A review
      of randomized controlled trials and systematic reviews.
AB  - BACKGROUND: Complementary medicine has become popular throughout many Western
      countries and is widely used by women across all stages of their life cycle.
      Acupuncture is used by women during their pregnancy, and research suggests that
      acupuncture may be used as an adjunct to their existing conventional care. The
      aim of this paper was to summarize the evidence examining the effectiveness of
      acupuncture during pregnancy and birthing, and to discuss its role as an adjunct
      treatment. METHODS: We conducted a systematic literature search using several
      electronic databases. We included all placebo-controlled randomized trials of
      parallel design, and systematic reviews that evaluated the role of acupuncture
      during pregnancy and birthing. A critical appraisal of clinical trials and
      systematic reviews was undertaken. RESULTS: The summarized findings indicated a
      small but growing body of acupuncture research, with some evidence suggesting a
      benefit from acupuncture to treat nausea in pregnancy. Findings from the review
      also highlighted promising evidence for the effectiveness of acupuncture to
      manage back and pelvic pain, acupuncture-type interventions to induce change in
      breech presentation, and pain relief in labor. The methodological quality of
      recent trials has improved, and the quality of systematic reviews was high.
      CONCLUSIONS: Interest is growing in the use of acupuncture to treat some
      complaints during pregnancy and childbirth, and evidence is beginning to
      consolidate that acupuncture may assist with the management of some complaints
      during pregnancy. However, definitive conclusions about its effectiveness cannot
      be reached and further research is justified.

PMID- 19747274
TI  - Letter from Europe: water birth: just a fad?

PMID- 19747278
TI  - Pacifiers and breastfeeding.

PMID- 19747279
TI  - Preventing cerebral palsy: paths not (yet) taken.

PMID- 19747280
TI  - Impairment severity selectively affects the control of proximal and distal
      components of reaching movements in children with hemiplegic cerebral palsy.
AB  - This study explored proximal-to-distal components during goal-directed reaching
      movements in children with mild or moderate hemiplegic cerebral palsy (HCP);
      [seven females, four males; mean age 8 y 6 mo; SD 27 mo], compared with age
      matched, typically developing children (seven females, five males; mean age 8 y 3
      mo [SD 25 mo]. Severity of HCP was assessed following the approach of Claeys et
      al. Optoelectronic registrations were made during unimanual reaching-to-grasp and
      reaching-to-hit movements with both the affected/non-preferred and
      unaffected/preferred side. Regardless of task, the children with HCP,
      particularly those with moderate impairment, displayed less optimal
      spatiotemporal organization of movements performed with the affected arm.
      Compared with the goal to hit, and increasingly with more severe impairment,
      children with HCP adapted to the goal to grasp by recruiting augmented shoulder
      movements when reaching with the affected side. A resulting impact on distal
      kinematics was found in shorter, straighter, and less segmented movement paths.
      Thus, depending on severity of hemispheric lesions and task complexity,
      unilateral brain injuries in HCP may selectively affect neural pathways
      underlying both proximal and distal arm movement control. Levels of both ipsi-
      and contralateral activation in relation to side and lesion severity should be
      considered in future studies on prehension movements in HCP.

PMID- 19747281
TI  - Effectiveness of sedation using nitrous oxide compared with enteral midazolam for
      botulinum toxin A injections in children.

PMID- 19747282
TI  - Anterior to posterior limb of the internal capsule morphology in fragile X
      syndrome.

PMID- 19747284
TI  - Professor Alan Harold Waters MBBS(Hons), PhD, FRCPA, FRACP, FRCPath, FRCP (1934
      2009).

PMID- 19747285
TI  - Clinical stem cell therapies for severe autoimmune diseases.
AB  - Severe autoimmune diseases (ADs) are a major source of disability and reduced
      quality of life and may result in shortened life expectancy, particularly in
      treatment-resistant patients. For several decades, allogeneic and autologous
      haematopoietic stem cell transplantation (HSCT) has been the focus of scientific
      investigation as a potential means of delivering 'one-off' intensive treatment in
      severe ADs. Improvements in the clinical safety of HCST were followed by its
      increasing use in recent years as an experimental treatment for severe and
      resistant ADs. European and North American registries have accumulated between
      one and two thousand procedures. Retrospective analyses and prospective studies
      have demonstrated the feasibility, safety and initial efficacy data in various
      ADs. Profound cell biological changes induced by HSCT leading to stabilization or
      reversal of organ damage have been characterized. These have also shed light on
      basic disease mechanisms and support investigation of more specific cellular
      therapy in ADs. There is clear potential for harnessing a profound immunological
      effect through HSCT. However, there is a need for an ongoing balance against
      evolving non-transplant treatments for ADs. Ideally, these issues should be
      resolved in phase III studies, in which HSCT approaches are compared with the
      best comparator.

PMID- 19747286
TI  - Two novel null alleles of the KEL gene detected in two Chinese women with the
      K(null) phenotype.
AB  - In screening 87665 unrelated healthy blood donors in China, serology studies
      resulted in the detection of two K(0) probands, both female. To explore the
      molecular basis of the K(null) phenotype in the Chinese population, genomic DNA,
      total RNA, and reticulocyte RNA were subsequently prepared from the two probands,
      five family members of proband 1, four unrelated normal controls, and one
      unrelated KEL1 control. Nucleic acids were analyzed for the KEL gene by DNA and
      RNA sequencing, while antigens were analyzed by flow cytometry with BRIC18,
      BRIC68, anti-k, and anti-Kp(b). Two novel K(null) alleles were identified in both
      probands: in exon 3, 185insT (Ser62Phe and a premature stop codon in exon 4,
      GenBank accession number, EF208900), and in exon 7, 715G>T (Glu239Stop, GenBank
      accession number EF208901). Alternative splicing patterns were observed in RNA
      obtained from whole blood versus from a reticulocyte fraction. Our study
      identified these two novel K(null) alleles resulting in the K(null) phenotype,
      the frequency of the K(null) phenotype amongst Chinese mainlanders is only
      0.00228%.

PMID- 19747287
TI  - Iron deficiency and frequency of HFE C282Y gene mutation in Brazilian blood
      donors.
AB  - Limited data are available about iron deficiency (ID) in Brazilian blood donors.
      This study evaluated the frequencies of ID and iron-deficiency anaemia (IDA)
      separately and according to frequency of blood donations. The protective effect
      of the heterozygous genotype for HFE C282Y mutation against ID and IDA in female
      blood donors was also determined. Five hundred and eight blood donors were
      recruited at the Blood Bank of Santa Casa in Sao Paulo, Brazil. Haemoglobin and
      serum ferritin concentrations were measured. The genotype for HFE C282Y mutation
      was determined by polymerase chain reaction followed by restriction fragment
      length polymorphism analysis. The ID was found in 21.1% of the women and 2.6% of
      the men whereas the IDA was found in 6.8 and 0.3%, respectively. The ID was found
      in 11.9% of the women in group 1 (first-time blood donors) and the frequency
      increased to 38.9% in women of the group 3 (blood donors donating once or more
      times in the last 12 months). No ID was found in men from group 1; however the ID
      frequency increased to 0.9% in group 2 (who had donated blood before but not in
      the last 12 months) and 5.0% in group 3. In summary, the heterozygous genotype
      was not associated with reduction of ID or IDA frequencies in both genders, but
      in male blood donors it was associated with a trend to elevated ferritin levels
      (P = 0.060). ID is most frequent in Brazilian women but was also found in men of
      group 3.

PMID- 19747288
TI  - Retrospective surveillance of HIV prevalence in blood donors can help in the
      selection of the best social group for blood donation in Mali.
AB  - The National Centre for Blood Transfusion, Bamako, Mali has collected data that
      characterizes trend in HIV prevalence over 10 years by gender, age, occupation,
      marital status and donor category. These data help to describe national HIV
      prevalence and assist in formulating blood donation policies. Donations from 1993
      to 2002 were categorized by donor age (decade), occupation (student, military and
      other), marital status (single, married and other), gender and donor status
      (volunteer, occasional and family). Comparisons were made using conservative
      estimates of donation frequency/donor category. Donations increased by more than
      400%. By 1999, increased HIV prevalence in donations from women was consistently
      present. Donations from the age group of 30-39 years showed an increased
      prevalence beginning in 2000, which by 2002 was almost 10 times greater than in
      the low-prevalence (<20 years) group (5.9 vs. 0.6%). By 2000, both categories -
      students and military were less likely to be HIV positive than those from other
      occupational categories, and donations from married persons were less likely to
      be HIV positive by 1997. The highest prevalence was observed in the 'occasional'
      donor category, which increased to >14% by 2001; volunteer donation HIV positive
      peaked at 2.3% in 1999. HIV prevalence in blood donations in Bamako, Mali,
      demonstrates important trends from 1993 to 2002. The prevalence of > 14% in
      donations from occasional donors and significant trends by decade, gender,
      marital status and occupation argue for increased analysis of the blood donor
      population to improve blood safety and to understand the demographics of HIV
      infection in Mali.

PMID- 19747289
TI  - Clinical efficacy and safety of Flebogammadif, a new high-purity human
      intravenous immunoglobulin, in adult patients with chronic idiopathic
      thrombocytopenic purpura.
AB  - Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder characterized
      by a low platelet count and bleeding, whose incidence is approximately 6.2 for
      each 100,000 adults per year. Intravenous immunoglobulins (IVIG) can be useful in
      patients with ITP to prevent bleeding or prior to surgery. In this study, the
      efficacy and safety of Flebogammadif, a new high-purity IVIG, were assessed by an
      open, multicentre, non-controlled, prospective study in adult patients with
      chronic ITP. A total of 20 patients (enrolled if experiencing chronic ITP since
      at least 6 months before recruitment and if platelet count <20 x 10(9)L(-1)
      before treatment) received 0.4 g kg(-1)-bw of Flebogammadif for 5 consecutive
      days and were followed-up for 3 months. Efficacy endpoints were three: proportion
      of patients who reached a platelet count > or = 50 x 10(9)L(-1), time for the
      platelet count to reach that level and duration of response. Safety parameters
      [adverse events (AE), laboratory determinations and vital signs] and viral
      markers were regularly monitored. A total of 14 patients achieved a platelet
      count of > or = 50 x 10(9)L(-1). The median time to platelet response was </=2.5
      days, and the median number of days in which the platelet count remained > or =
      50 x 10(9)L(-1) was > or = 7 days. A regression of haemorrhages was reported for
      17 patients on day 14. Eight patients presented 21 AEs (mostly mild) potentially
      related to the study drug. Neither abnormalities in laboratory values nor in
      viral markers were registered during the follow-up period. Flebogammadif was well
      tolerated and succeeded in providing a haemostatic platelet count in patients
      with ITP.

PMID- 19747290
TI  - Platelet-specific alloantigens and antibodies in Tunisian women after three or
      more pregnancies.
AB  - Pregnancy may allow alloimmunization against human platelet antigens (HPA), which
      can lead to neonatal alloimmune thrombocytopenia (NAIT). The specificities of
      alloantibodies are closely related to the distribution of the HPA systems. A
      total of 281 Tunisian multiparous women (mean number of pregnancies: 4.5) were
      phenotyped for the HPA-1, -3 and -5 systems, by monoclonal antibody
      immobilization of platelet antigens (MAIPA). We searched for antibodies against
      HPA-1a, HPA-3a, HPA-5b and HPA-5a in HPA-1b1b, HPA-3b3b, HPA-5a5a and HPA-5b5b
      individuals, respectively. The gene frequencies were: 0.83 for HPA-1a, 0.17 for
      HPA-1b, 0.78 for HPA-3a, 0.22 for HPA-3b, 0.82 for HPA-5a and 0.18 for HPA-5b.
      Anti-HPA-5b antibodies were present in eight sera and anti-HPA-3a antibodies were
      present in one serum. The anti-HPA-5b system is the most frequently involved in
      platelet alloimmunization in Tunisian multiparous women. However, prospective
      trials are required to confirm this result and to determine the exact frequencies
      and clinical relevance of platelet alloantibodies in pregnant Tunisian women.

PMID- 19747291
TI  - Application of the basophil activation test in the analysis of allergic
      transfusion reactions.

PMID- 19747293
TI  - Dignity in the life of people with head injuries.
AB  - TITLE: Dignity in the life of people with head injuries. AIM: This paper is a
      report of a study conducted to determine how people who suffer from head injuries
      perceive respect for their dignity and to discover what patients mean by the
      concept of 'dignity'. BACKGROUND: We know something about what the phenomenon of
      dignity means. However, we still lack knowledge about how patients perceive
      dignity in their lives and how dignity may be fostered and supported. METHODS:
      Qualitative interviews were carried out during 2007 with 14 patients suffering
      from head injuries, diagnosed as having mild to moderate disability. The study
      was explorative and descriptive, with a content analysis. FINDINGS: Patients
      experienced their dignity as maintained when they were taken seriously, received
      appropriate information and were reality-oriented. They experienced their dignity
      as violated if they had been neglected or had encountered healthcare personnel
      who lacked knowledge, were sceptical about their stories, and where the patient
      experienced extra burden when they were mistrusted. The importance of adequate
      information was underscored. As interviewees said, head injuries do not show on
      the outside and people with head injuries do not have a high status in society.
      CONCLUSION: Patients living with head injuries should be informed about
      consequences and be taught strategies for how to live with head injuries as early
      as possible after the injury in order to maintain dignity.

PMID- 19747294
TI  - Anxiety, depression and perceived control in patients having coronary artery
      bypass grafts.
AB  - TITLE: Anxiety, depression and perceived control in patients having coronary
      artery bypass grafts. AIM: This paper is a report of a study to determine (1) the
      course of anxiety, depression and perceptions of control, and (2) the influence
      of perceptions of control, in patients undergoing coronary artery bypass grafts
      before surgery, after surgery in hospital and 2 weeks after discharge.
      BACKGROUND: Anxiety and depression are common in patients undergoing coronary
      artery bypass graft surgery patients and predictive of worse outcomes. Few
      researchers have examined the influence of perceived control on these emotional
      states in the acute surgical period. METHODS: A prospective, descriptive design
      was used with a convenience sample of patients having coronary grafts (n = 155).
      Anxiety and depression were measured by the Hospital Anxiety and Depression Scale
      and perceptions of control over their cardiac illness by the Control Attitudes
      Scale before surgery, after surgery during hospitalization and 2 weeks after
      hospital discharge. The data were collected in 2005. RESULTS: Patients had low
      levels of anxiety at each timepoint; however, borderline or clinically
      significant levels were common before surgery (38.7%) and after discharge.
      (38.6%). Depression levels were low, but increased over time (F = 27.03, P <
      0.001). Patients had low to moderate perceptions of control over their illness
      before surgery, which increased over time (F = 25.51, P < 0.001). Those with
      stronger perceptions of control were less anxious or depressed at all times and
      those who were more anxious or depressed before surgery continued to be so
      afterwards. CONCLUSION: Routine assessment of anxiety, depression and perceptions
      of control are justified to identify patients at risk and to intervene to promote
      control perceptions.

PMID- 19747295
TI  - Healthcare routines of university students with Type 1 diabetes.
AB  - TITLE: Healthcare routines of university students with Type 1 diabetes. AIM: This
      paper is a report of a study examining the benefits that university students with
      Type 1 diabetes associate with diabetes self-care routines, and the barriers that
      they experience in enacting self-care routines in the university environment.
      BACKGROUND: Many young adults with Type 1 diabetes attend university, and it is
      thought that these students might experience difficulties with their self-care
      routines while they are there. METHOD: A qualitative method was chosen to explore
      students' own perspectives. Seventeen students with diabetes were interviewed
      twice, and each kept a research diary for a 2-week period. Interviews and diaries
      were analyzed using standard qualitative techniques. The study was conducted in
      2004-2005. FINDINGS: Routines had a number of identity-producing benefits for
      students. However, students often experienced difficulties routinizing their self
      care practices at university. These difficulties stemmed both from the irregular
      nature of university life and from students' desires not to let their diabetes
      interfere with their student lives. Most participants learned to adjust to
      university and enact self-care routines, although they could still experience
      routine difficulties during times of transition and stress. CONCLUSION:
      Healthcare professionals need to be aware of the difficulties that university
      students with Type 1 diabetes experience with their self-care routines. This
      awareness needs to encompass older students in the second, third and fourth years
      of their undergraduate degrees and postgraduate students as well as students in
      their first year at university.

PMID- 19747296
TI  - Linear IgA bullous dermatosis of childhood: successful treatment with miocamycin
      and topical corticosteroid.

PMID- 19747297
TI  - Dermatoscopy in the diagnosis of combined desmoplastic trichoepithelioma and
      naevus.

PMID- 19747298
TI  - Infection-like acral cutaneous metastasis as the presenting sign of an occult
      breast cancer.

PMID- 19747299
TI  - A linear basal cell carcinoma undergoing spontaneous regression.

PMID- 19747300
TI  - A first case of lichen sclerosus with Turner's syndrome.

PMID- 19747301
TI  - Severe psoriasis, morbid obesity and bariatric surgery.

PMID- 19747302
TI  - Scleroedema adultorum associated with sarcoidosis.

PMID- 19747303
TI  - Churg-Strauss syndrome secondary to antileucotriene therapy in a patient not
      receiving oral corticosteroids.

PMID- 19747304
TI  - Verruca plus acrochordon: an 'over the top' skin tag.

PMID- 19747305
TI  - A dual-wavelength approach with 585-nm pulsed-dye laser and 800-nm diode laser
      for treatment-resistant port-wine stains.

PMID- 19747306
TI  - Serum zinc levels in Iranian patients with acne.

PMID- 19747307
TI  - A rare linear atrophic lesion on the face.

PMID- 19747308
TI  - Marked response of burning mouth syndrome to pregabalin treatment.

PMID- 19747309
TI  - Efficacy of high-energy copper bromide laser (511 and 578 nm) with for deep
      infantile haemangioma.

PMID- 19747310
TI  - Disseminated varicella zoster infection in a patient with rheumatoid arthritis
      treated with methotrexate.

PMID- 19747311
TI  - Cutaneous blisters as the presenting signs of recurrent thyroglossal duct cyst in
      a child.

PMID- 19747312
TI  - Proliferating trichilemmal cyst of the vulva.

PMID- 19747313
TI  - A morphological comparison of a mixed tumour of the skin on the nasal tip:
      magnetic resonance imaging and histopathological features.

PMID- 19747314
TI  - Unusual location of purpura fulminans associated with acquired protein C
      deficiency and administration of propylthiouracil.

PMID- 19747315
TI  - Explaining a hitherto nameless condition: 'SKINTED'.

PMID- 19747316
TI  - Peyronie's disease associated with methotrexate therapy.

PMID- 19747317
TI  - Cocaine-induced midline destructive lesion.

PMID- 19747318
TI  - Prurigo nodularis-like skin eruptions after bomb-blast injury.

PMID- 19747319
TI  - Granuloma annulare of childhood successfully treated with potent topical
      corticosteroids previously unresponsive to tacrolimus ointment 0.1%: report of
      three cases.

PMID- 19747320
TI  - Cyclophosphamide and amniotic membrane transplantation in the management of
      ocular disease in a case of antiepiligrin cicatricial pemphigoid.

PMID- 19747321
TI  - Subacute cutaneous lupus erythematosus associated with breast carcinoma.

PMID- 19747322
TI  - 'Western' or 'Asian' intravascular large B-cell lymphoma?

PMID- 19747323
TI  - A fatal case of toxic epidermal necrolysis with extensive intestinal involvement.

PMID- 19747324
TI  - Lightning-strike granuloma.

PMID- 19747325
TI  - Delusional parasitosis by proxy.

PMID- 19747326
TI  - Facial acne during topical pimecrolimus therapy for vitiligo.

PMID- 19747327
TI  - Morphoea (localized scleroderma): baseline body surface involvement and
      antinuclear antibody may have a prognostic value.

PMID- 19747328
TI  - Recurrent pigmented eccrine porocarcinoma presenting as carcinoma erysipeloides.

PMID- 19747329
TI  - Presence of eosinophils in the inflammatory infiltrate of nonsegmental vitiligo:
      a retrospective study.

PMID- 19747330
TI  - A novel deletion mutation in the human hairless (HR) gene in an Iranian family
      with atrichia and papular lesions.

PMID- 19747331
TI  - A rare case of porokeratosis ptychotropica and coexistent linear porokeratosis in
      a 10-year-old boy.

PMID- 19747332
TI  - A 9-year-old girl with rhabdomyolysis complicated with iatrogenic calcinosis
      cutis.

PMID- 19747333
TI  - Intramuscular human immunoglobulin therapy for multiple warts: retrospective
      review of 10 patients.

PMID- 19747334
TI  - Successful treatment of dissecting cellulitis with ciprofloxacin.

PMID- 19747335
TI  - Serum lead levels in childhood eczema.

PMID- 19747336
TI  - Human T-cell lymphotrophic virus tropical paraparesis, hyperhidrosis and
      Norwegian scabies.

PMID- 19747337
TI  - The Kobner response of lichen planus occurring in abdominal striae.

PMID- 19747338
TI  - Pterygium inversum unguis: aberrantly regulated keratinization in the nail
      isthmus.

PMID- 19747339
TI  - Consensus statement on the management of chronic hand eczema.
AB  - The management of chronic hand eczema is often inadequate. There are currently no
      evidence-based guidelines specifically for the management of chronic hand eczema,
      and evidence for established treatments for hand eczema is not of sufficient
      quality to guide clinical practice. This consensus statement, based on a review
      of published data and clinical practice in both primary and secondary care, is
      intended to guide the management of chronic hand eczema. It describes the
      epidemiology and pathogenesis of hand eczema, its diagnosis and its effect on
      patients' quality of life. Management strategies include a skin education
      programme, lifestyle changes, and the use of emollients, barriers and soap
      substitutes. Topical drug therapy includes topical steroids and calcineurin
      inhibitors. Treatment with psoralen ultraviolet A and systemic therapies may then
      be appropriate, although there is no strong evidence of efficacy. Alitretinoin
      has been shown to be effective in a randomized controlled trial, and is currently
      the only treatment specifically licensed for the treatment of hand eczema.
      Recommendations for management are summarized in a treatment algorithm.

PMID- 19747340
TI  - Monoallelic expression on autosomes may explain an unusual heritable form of
      pigmentary mosaicism: a historical case revisited.
AB  - A peculiar observation published in 1971 by Chernosky et al. is revisited in this
      paper. An African American mother and three of her four children (two girls and
      one boy) had hyperpigmented skin areas arranged along Blaschko's lines. According
      to the current knowledge of formal genetics, a mendelian mode of transmission can
      be excluded, and paradominant inheritance is likewise highly unlikely. The
      unusual family constellation of pigmentary mosaicism can be best explained as an
      example of monoallelic autosomal expression, a concept that is now well
      established in the genetics of plants and animals but so far unexplored in human
      skin disorders. Either the paternal or the maternal allele is randomly
      inactivated, therefore this mechanism can be taken as an autosomal counterpart of
      X-chromosome inactivation. Recent studies suggest that 5-10% of autosomal human
      genes are monoallelically expressed. This theory opens a new field of research in
      dermatology. Clinicians should consider this new aetiological concept when
      observing cases of hereditary cutaneous mosaicism that cannot be explained by X
      linkage.

PMID- 19747341
TI  - Iatrogenic Kaposi's sarcoma in a patient with pemphigus vulgaris.

PMID- 19747342
TI  - Multiple white facial papules.

PMID- 19747343
TI  - Progressive chronic nasal enlargement with an overlying violaceous plaque.

PMID- 19747344
TI  - A papule with bluish ring on the chest.

PMID- 19747346
TI  - Influence of climate and reproductive timing on demography of little brown myotis
      Myotis lucifugus.
AB  - 1. Estimating variation in demographic rates, such as survival and fecundity, is
      important for testing life-history theory and identifying conservation and
      management goals. 2. We used 16 years (1993-2008) of mark-recapture data to
      estimate age-specific survival and breeding probabilities of the little brown
      myotis Myotis lucifugus LeConte in southern New Hampshire, USA. Using Kendall &
      Nichols' (1995) full-likelihood approach of the robust design to account for
      temporary emigration, we tested whether survival and breeding propensity is
      influenced by regional weather patterns and timing of reproduction. 3. Our
      results demonstrate that adult female survival of M. lucifugus ranged from 0.63
      (95% CL = 0.56, 0.68) to 0.90 (95% CL = 0.77, 0.94), and was highest in wet years
      with high cumulative summer precipitation. First-year survival [range: 0.23 (95%
      CL = 0.14, 0.35) to 0.46 (95% CL = 0.34, 0.57)] was considerably lower than adult
      survival and depended on pup date of birth, such that young born earlier in the
      summer (c. late May) had a significantly higher probability of surviving their
      first year than young born later in the summer (c. mid-July). Similarly, the
      probability of young females returning to the maternity colony to breed in the
      summer following their birth year was higher for individuals born earlier in the
      summer [range: 0.23 (95% CL = 0.08, 0.50) to 0.53 (95% CL = 0.30, 0.75)]. 4. The
      positive influence of early parturition on 1st-year survival and breeding
      propensity demonstrates significant fitness benefits to reproductive timing in
      this temperate insectivorous bat. 5. Climatic factors can have important
      consequences for population dynamics of temperate bats, which may be negatively
      affected by summer drying patterns associated with global climate change. 6.
      Understanding long-term demographic trends will be important in the face of a
      novel disease phenomenon (White-Nose Syndrome) that is associated with massive
      mortalities in hibernating bat species, including M. lucifugus, in the
      northeastern United States.

PMID- 19747347
TI  - Racist appearance standards and the enhancements that love them: Norman Daniels
      and skin-lightening cosmetics.
AB  - Darker skin correlates with reduced opportunities and negative health outcomes.
      Recent discoveries related to the genes associated with skin tone, and the
      historical use of cosmetics to conform to racist appearance standards, suggest
      effective skin-lightening products may soon become available. This article
      examines whether medical interventions of this sort should be permitted,
      subsidized, or restricted, using Norman Daniels's framework for determining what
      justice requires in terms of protecting health. I argue that Daniels's expansive
      view of the requirements of justice in meeting health needs offers some support
      for recognizing a societal obligation to provide this kind of 'enhancement,' in
      light of the strong connections between skin tone and health outcomes. On
      balance, however, Daniels's framework offers compelling reasons to reject
      insurance coverage for skin-lightening medical interventions, including the
      likely ineffectiveness of such technologies in mitigating racial health
      disparities, and the danger that covering skin-lightening enhancements would
      undermine public support for cooperative schemes that protect health. In fact,
      justice may require limiting access to these technologies because of their
      potential to exacerbate the negative effects of racism.

PMID- 19747348
TI  - Cut-off values and significance of Oil Red O-positive cells in bronchoalveolar
      lavage fluid.
AB  - OBJECTIVE: To evaluate the percentage and predictive value of Oil Red O-positive
      macrophages (ORO-PM) to identify lipid-laden macrophages in bronchoalveolar
      lavage fluids (BALF) from patients with different pathologies. METHODS: The
      percentage and absolute numbers of ORO-PM were evaluated in 305 BALF. The
      patients were separated into ten groups: corticosteroid treatment (n = 18),
      amiodarone treatment (n = 8), interstitial fibrosis (n = 11), human
      immunodeficiency virus (HIV)-positive (n = 25), infectious pneumonia (n = 43),
      severe haematological disorder (n = 25), interstitial syndrome (n = 109),
      suspicion of cancer (n = 17), transplant recipients (n = 50) and controls (n =
      43). The total and differential cell counts in BALF were recorded. The presence
      of specific pathogens was also noted. Parametric and non-parametric tests were
      used to compare the values between groups. Receiver-operating characteristics
      (ROC) curves were established in order to determine a cut-off value. RESULTS: The
      percentages of ORO-PM were (mean +/- standard deviation) 21.67 +/- 29.12 in the
      corticosteroid group, 10.00 +/- 12.49 in the amiodarone group, 19.45 +/- 20.72 in
      the interstitial fibrosis group, 47.80 +/- 30.46 in the HIV group, 19.72 +/-
      26.26 in the infectious pneumonia group, 27.42 +/- 30.04 in the severe
      haematological disorder group, 25.18 +/- 30.63 in the interstitial syndrome
      group, 17.64 +/- 27.76 in the suspicion of cancer group, 22.50 +/- 27.27 in the
      transplanted recipients group and 2.63 +/- 3.48 in the control group.
      Significantly higher values were found in all groups when compared with the
      control group (P < 0.001). Only the HIV group showed higher numbers of ORO-PM
      when compared with the interstitial syndrome group (P < 0.01). According to ROC
      curves, > 6% ORO-PM was suggested as the positive cut-off value. CONCLUSION:
      Significantly increased numbers of ORO-PM were associated with various lung
      pathologies. However, the higher numbers observed in HIV patients require further
      investigations.

PMID- 19747349
TI  - Different roles of Foxo1 and Foxo3 in the control of endothelial cell morphology.
AB  - Foxo1, a member of the Foxo subfamily of forkhead box transcription factors, is
      known to be essential for progression of normal vascular development in the mouse
      embryos. In the cultures of endothelial cells derived from embryonic stem cells,
      Foxo1-deficient endothelial cells exhibit an abnormal morphological response to
      vascular endothelial growth factor-A (VEGF-A), which is characterized by a lack
      of cell elongation, yet the molecular mechanisms governing endothelial cell
      morphology under angiogenic stimulation remain unknown. Here, we report that
      transforming growth actor-beta also induces endothelial cell elongation in
      collaboration with Foxo1 and VEGF-A. Furthermore, tetracycline-regulated
      induction of Foxo3, another member of the Foxo subfamily, into Foxo1-null
      endothelial cells failed to restore abnormal morphological response to VEGF-A at
      an early differentiation stage. In contrast, Foxo1 and Foxo3 exerted the same
      function at a late differentiation stage, i.e. enhancement of VEGF responsiveness
      and promotion of cell elongation. Our results provide evidence that endothelial
      cell morphology is regulated by several mechanisms in which Foxo1 and Foxo3
      express distinct functional properties depending on differentiation stages.

PMID- 19747350
TI  - How are we going to turn the obesity prevention experience?

PMID- 19747351
TI  - Reclassification of odontogenic keratocyst as tumour. Impact on the odontogenic
      tumours prevalence.
AB  - AIM: The aim of this study was to establish the impact of the redefinition and
      reclassification of odontogenic keratocyst (OKC) as a tumour on the prevalence of
      odontogenic tumours (OT). METHODS: We revised 15 435 files of a teaching head and
      neck histopathology service in the time period from January 1981 to December 2008
      and 478 cases of OT were selected. The 342 cases from 1981 to 2004 were
      classified according 1992 to the World Health Organization (WHO)-classification
      (excluding keratocystic OT) while the 136 cases from 2005 onwards were classified
      according to the 2005 WHO-classification (including keratocystic OT). Age and
      gender were obtained from medical records. The frequency distribution and
      prevalence of OT from each periods of time were compared. A chi-square test was
      performed (P < 0.05 95% confidence interval). RESULTS: The prevalence of OT
      increases 92% in the 2005-2008 period; from 2.6% (1981-2004 period) to 5% (2005
      2008 period) (P 0.000).The most frequent OT in the 1981-2004 period was odontoma
      (45% of all OT) while in the 2005-2008 period was Keratocystic Odontogenicv
      Tumour (38.9%). CONCLUSIONS: The redefinition of OKC as a tumour produced an
      increase in the frequency and prevalence of OT.

PMID- 19747352
TI  - Clinical experience in a modified Roux-Y-shaped sigmoid neobladder: assessment of
      complications and voiding patterns in 43 patients.
AB  - OBJECTIVE: To evaluate the complications and urinary voiding patterns in patients
      with a new Roux-Y-shaped continent neobladder, using a modified sigmoid pouch.
      PATIENTS AND METHODS: Between June 2003 and July 2008, 43 patients (26 men and 17
      women, mean age 69.5 years) underwent a modified Roux-Y-shaped sigmoid continent
      neobladder reconstruction after radical cystectomy. The surgical procedures
      involved the construction of a Roux-Y-shaped sigmoid pouch, making an antifeces
      refluxing valve into the sigmoid urine reservoir and ureterosigmoidostomy using
      the Leadbetter method. This pouch method has not been described before. The
      patients' clinical, biochemical, radiological and urodynamic variables were
      assessed. RESULTS: During the mean (range) follow-up of 24 (6-65) months, there
      were no deaths related to the procedure. In 16% of the patients, early
      complications occurred, whereas 12% had late complications. There were no cases
      with local recurrence and metastasis. Routine electrolyte evaluation revealed a
      slight metabolic acidosis in six patients (14%). Hypovitaminosis B(12) did not
      occur in any patients. All patients were continent in the daytime and night-time
      continence was poor in eight patients (19%). The mean (sd, range) neobladder
      capacity and residual urine volume was 330 (110, 120-410) mL and 48 (26, 25-80)
      mL, respectively. Moreover, the maximum urinary flow rate was 9.2-25.3 mL/s.
      CONCLUSION: The modified Roux-Y-shaped sigmoid neobladder replacement provides a
      new simple surgical procedure with low complication rates. The procedure offers
      comparatively satisfactory daytime continence with low postvoid residual urine
      volumes and voiding patterns. This technique is a valid alternative to continent
      urinary diversion.

PMID- 19747353
TI  - Morbidity of open retroperitoneal lymph node dissection for testicular cancer:
      contemporary perioperative data.
AB  - OBJECTIVE: To review differences between primary retroperitoneal lymph node
      dissection (P-RPLND) and RPLND after chemotherapy (PC-RPLND) in a contemporary
      series of patients with testicular cancer, to validate the proposed low
      morbidity. PATIENTS AND METHODS: Patients who had undergone RPLND at our
      institution in 2001-2008 were identified and their clinical charts reviewed; in
      all, 190 were identified and perioperative data obtained. RESULTS: Of the 190
      patients who had RPLND, 98 (52%) and 92 (48%) had P- and PC-RPLND, respectively.
      Histology of the orchidectomy specimen consisted of embryonal carcinoma in 146
      (76%) patients, also including lymphovascular invasion in 83 (44%). The mean
      (range) operative duration was 206 (110-475) min and the mean blood loss was 294
      (50-7000) mL. The median hospital stay was 4 days. Mean blood loss, operative
      duration and hospital stay were significantly less for the P-RPLND than for PC
      RPLND groups (P < 0.05). There were 18 (9%) perioperative complications in all.
      There were no deaths in either group. CONCLUSIONS: The short-term morbidity of
      open RPLND is acceptable, and open RPLND is safe and effective at select tertiary
      centres. When compared with historical data, the present contemporary series
      shows that the operative duration, blood loss and hospital stay have improved,
      with few complications. These contemporary data should be considered when
      comparing laparoscopic with open RPLND.

PMID- 19747354
TI  - Mid-urethral synthetic slings in the treatment of urodynamic female stress
      urinary incontinence without concomitant pelvic prolapse repair: 4-year health
      related quality of life outcomes.
AB  - OBJECTIVE: To report 4-year health-related quality of life (HRQL) outcome data
      after retropubic mid-urethral synthetic sling (MUS) surgery without concomitant
      prolapse repair for treating female stress urinary incontinence (SUI) in a single
      institution. PATIENTS AND METHODS: The data were prospectively collected, which
      yielded 21 consecutive patients with a mean (range) age of 67.6 (41-81) years who
      underwent retropubic MUS with > or = 4 years follow-up. Before surgery, all
      patients underwent history, examination, pad usage, and multichannel fluoroscopic
      urodynamics according to International Continence Society standards. In all, 19
      patients had urethral hypermobility with an abdominal leak-point pressure (ALPP)
      of >90 cmH(2)O and two had intrinsic sphincter deficiency with an ALPP of <60
      cmH(2)O. The MUS were all placed under no tension. All patients were cystoscoped
      with both 30 and 70 degrees lens at the end of the procedure with a fully
      distended bladder to exclude bladder or urethral injury. The validated Kings
      Health Questionnaire (KHQ) was used both before and after surgery to assess HRQL
      measures. All patients were assessed at 3 months, and then at least three times
      thereafter. RESULTS: The paired Student's t-test was used on the mean KHQ scores
      before and after MUS surgery (4 years follow-up). There were statistically
      significant improvements in all nine domains on the KHQ between preoperative and
      3 months after MUS surgery (P < 0.01), with the most significant being in
      'General Health Perceptions', 'Incontinence Impact', 'Physical Limitations', and
      'Role Limitations'. Improvement in HRQL persisted up to 4 years in all domains.
      Bladder perforation occurred in two patients with uneventful resolution. Two
      patients required very short-term catheterization (<5 days). In the present
      series, there was no sling revision, division, infection or erosion. No patients
      developed de novo urgency or urge UI after MUS surgery. The pad-free rate in the
      present series was 85.7%. CONCLUSION: In our institution, HRQL improvement at 3
      months after retropubic MUS surgery predicts persistence of improvement at 4
      years. This is useful clinically in counselling our patients for treatment
      efficacy. Tension-free placement is associated with minimal risk of postoperative
      retention or de novo overactive bladder. Although patient numbers are modest,
      these data contribute to the scarce longer term (> or =4 years) HRQL data on the
      MUS, which is a safe and durable procedure with a minimal complication profile.

PMID- 19747355
TI  - Penile rehabilitation protocol after robot-assisted radical prostatectomy:
      assessment of compliance with phosphodiesterase type 5 inhibitor therapy and
      effect on early potency.
AB  - STUDY TYPE: Therapy (case series). LEVEL OF EVIDENCE: 4. OBJECTIVE: To evaluate
      factors that affect compliance in men who enroll in a phosphodiesterase type 5
      inhibitor (PDE5I) protocol after nerve-sparing robot-assisted prostatectomy
      (RAP), and report on short-term outcomes, as PDE5Is may help restore erectile
      function after RAP and patient adherence to the regimen is a factor that
      potentially can affect outcome. PATIENT AND METHODS: We prospectively followed 77
      men who had nerve-sparing RAP and enrolled in a postoperative penile
      rehabilitation protocol. The men received either sildenafil citrate or tadalafil
      three times weekly. The minimum follow-up was 8 weeks. Potency was defined as
      erection adequate for penetration and complete intercourse. Compliance was
      defined as men adhering to the regimen for > or =2 months. RESULTS: The mean age
      of the cohort was 57.8 years and the median follow-up was 8 months. In all, 32%
      of the men discontinued the therapy <2 months after RAP and were deemed
      noncompliant with an additional 39% discontinuing therapy by 6 months, with the
      high cost of medication being the primary reason (65%). Long-term compliance and
      preoperative erectile dysfunction were independent predictors of potency return
      after adjusting for age and nerve sparing. CONCLUSIONS: The high cost of
      medication remains a significant barrier to maintaining therapy. Noncompliance to
      PDE5I therapy in a tertiary care centre was much higher than reported in clinical
      trial settings. With longer-term follow-up, we need to further define the factors
      that improve overall recovery of sexual function after RAP.

PMID- 19747356
TI  - Renal cell carcinoma in patients with end-stage renal disease: relationship
      between histological type and duration of dialysis.
AB  - OBJECTIVE: To evaluate the clinical outcomes and histological types of renal cell
      carcinoma (RCC) arising in patients with end-stage renal disease (ESRD), and to
      analyse the relationship of histopathological features with the duration of
      dialysis. PATIENTS AND METHODS: Clinical characteristics and outcomes of 34
      patients who had a radical nephrectomy for RCC arising in ESRD between November
      1994 and June 2008 were investigated. Archive paraffin-embedded tissue specimens
      obtained from 27 patients were histochemically and immunohistochemically analysed
      to determine the histopathological type. RESULTS: There was one death from cancer
      and one patient with local progression within a median observation period of 29.5
      months. Acquired cystic disease (ACD)-associated RCC, clear cell-papillary RCC,
      mucinous tubular and spindle-cell carcinoma, and Xp11.2 translocation/TFE3 gene
      fusion were identified in eight, two, three and one patient, respectively.
      Conventional clear-cell RCC was the predominant histological type (nine of 15) in
      patients with a duration of dialysis of <10 years, while ACD-associated RCC was
      predominant (seven of 12) in those with dialysis for > or =10 years. Sarcomatoid
      foci were identified in three patients with dialysis for > or =10 years.
      Papillary adenoma was microscopically identified as a satellite tumour in 10
      patients. CONCLUSION: The spectrum of histological types of RCCs arising in ESRD
      is distinct from that of sporadic RCCs. Patients with a longer duration of
      dialysis should have particular attention for progression and metastasis.
      Immunohistochemical profiling is efficient in the histological classification of
      RCCs arising in ESRD, although knowledge about genetic changes remains to be
      accumulated.

PMID- 19747357
TI  - Prostate cancer survivors who would be eligible for active surveillance but were
      either treated with radiotherapy or managed expectantly: comparisons on long-term
      quality of life and symptom burden.
AB  - OBJECTIVE: To assess and identify factors associated with the long-term health
      related quality of life (HRQL) of prostate cancer survivors managed expectantly,
      as patients with low-risk prostate cancer can be managed with active surveillance
      (AS), but research on associated long-term HRQL is scarce. PATIENTS AND METHODS:
      From the population-based Eindhoven Cancer Registry, 71 men managed with AS were
      matched with 71 survivors who had similar demographic and clinical
      characteristics but treated with external beam radiotherapy (RT). All were
      diagnosed between 1994 and 1998. HRQL data were collected 5-10 years after
      diagnosis. Patients completed generic- (Short Form-36) and cancer-specific
      (Quality of Life - Cancer Survivors) HRQL instruments, and symptom burden
      (Expanded Prostate Cancer Index, Sexual Activity) questionnaires. RESULTS:
      Patients on AS were comparable to those treated with RT for most generic- and
      disease-specific HRQL dimensions. Patients treated with RT had poorer mean (sd)
      bowel function scores, of 87.1 (13.1) vs 92.8 (10.7) (P < 0.001), more bother
      with bowel function, at 85.0 (16.4) vs 93.7 (10.1) (P < 0.001), and more problems
      with getting an erection (68% vs 47%, P = 0.005). Multivariate regression
      analyses (corrected for comorbidity and clinical disease progression) indicated
      that the management strategy independently predicted differences in physical
      functioning, bodily pain, spiritual and total well-being, and bowel function and
      bowel bother. CONCLUSIONS: Patients managed expectantly at initial diagnosis (AS)
      have comparable HRQL and a lower symptom burden than patients treated with RT up
      to 10 years after the diagnosis.

PMID- 19747358
TI  - Testosterone levels in patients with metastatic prostate cancer treated with
      luteinizing hormone-releasing hormone therapy: prognostic significance?
AB  - OBJECTIVE: To determine if the testosterone level achieved with androgen
      deprivation therapy (ADT) is directly related to survival and risk of death in
      men with metastatic prostate cancer, as agonistic analogues of luteinizing
      hormone-releasing hormones (LHRH) are indicated for palliative treatment of these
      patients, but there is no consensus about the utility of serum testosterone
      measurements during the follow-up, and their possible prognostic value. PATIENTS
      AND METHODS: We retrospectively reviewed 129 consecutive patients with a
      histological diagnosis of metastatic bony-only prostate cancer and previously
      untreated with ADT. They were treated with 3 months of goserelin. Testosterone
      and prostate-specific antigen (PSA) levels were measured in all patients every 3
      months for the duration of the follow-up. The following variables were recorded:
      age, stage, Gleason score, basal PSA level, basal testosterone level, PSA nadir,
      time to PSA nadir, testosterone after 6 months, testosterone nadir and time to
      testosterone nadir. Data were analysed using Cox's proportional hazards models,
      with the primary endpoint being cancer-specific survival. RESULTS: The mean (SD)
      basal PSA level was 185.8 (344.1) ng/mL, and the mean nadir PSA level 2.7 (8.6)
      ng/mL. The mean testosterone levels at baseline, 6 months and the nadir were 440
      (200), 40 (40) and 21 (15) ng/dL. With a mean follow-up of 47.5 (29.7) months, 71
      patients were dead (55%) and 78 were alive (45%) at the time of analysis.
      Statistical analysis using Cox's model showed that in these patients the risk of
      death was directly correlated not only to Gleason score (P < 0.01) and to the 6
      month PSA level (P < 0.01), but also to the 6-month serum testosterone level
      (hazard ratio 1.32, P < 0.05). CONCLUSION: These results suggest a direct
      correlation between the risk of death and testosterone levels achieved during
      ADT. Based on the present results, lowering the testosterone level as much as
      possible should be the goal of ADT in patients with metastatic prostate cancer,
      as this might affect patient survival.

PMID- 19747359
TI  - Impact of dermoscopy and short-term sequential digital dermoscopy imaging for the
      management of pigmented lesions in primary care: a sequential intervention trial.
AB  - BACKGROUND: Studies have shown the benign to malignant ratio of excised pigmented
      skin lesions is suboptimal in primary care. OBJECTIVES: To assess the impact of
      dermoscopy and short-term sequential digital dermoscopy imaging (SDDI) on the
      management of suspicious pigmented skin lesions by primary care physicians.
      METHODS: A total of 63 primary care physicians were trained in the use of
      dermoscopy and SDDI (interventions) and then recruited pigmented lesions
      requiring biopsy or referral in routine care by naked eye examination. They were
      then given a dermatoscope and the option of a SDDI instrument, and change of
      diagnosis and management was assessed. RESULTS: Following the use of the
      interventions on 374 lesions a total of 163 lesions (43.6%) were excised or
      referred, representing a reduction of 56.4%. Of the 323 lesions confirmed to be
      benign, 118 (36.5%) were excised or referred, leading to a reduction of 63.5% (P
      < 0.0005) in those requiring excision or referral. The baseline naked eye
      examination benign to melanoma ratio was 9.5 : 1 which decreased to 3.5 : 1 after
      the diagnostic interventions (P < 0.0005). Of the 42 malignant lesions included
      in the study (34 melanoma, six pigmented basal cell carcinoma and two Bowen
      disease) only one in situ melanoma was incorrectly managed (patient to return if
      changes occur) resulting in the correct management of 97.6% and 97.1% of
      malignant pigmented lesions and melanoma, respectively. CONCLUSIONS: In a primary
      care setting the combination of dermoscopy and short-term SDDI reduces the
      excision or referral of benign pigmented lesions by more than half while nearly
      doubling the sensitivity for the diagnosis of melanoma.

PMID- 19747360
TI  - Clofarabine, cyclophosphamide and etoposide as single-course re-induction therapy
      for children with refractory/multiple relapsed acute lymphoblastic leukaemia.
AB  - The safety and efficacy of the combination clofarabine/cyclophosphamide/etoposide
      were evaluated in children with advanced acute lymphoblastic leukaemia (ALL). The
      study enrolled 25 paediatric patients (median age 12.5 years) with either
      refractory (n = 17; 68%) or multiple relapsed (n = 8; 32%) ALL to receive
      clofarabine 40 mg/m(2), cyclophosphamide 400 mg/m(2) and etoposide 150 mg/m(2),
      daily for 5 consecutive days. No patient died from treatment-related
      complications. The most common adverse events were febrile neutropenia, mucositis
      and reversible liver toxicity; no case of liver veno-occlusive disease was
      reported. The overall remission rate was 56%: 13 patients (52%) achieved complete
      remission (CR) and one (4%) CR without platelet recovery (CRp). In seven of the
      13 (54%) patients achieving CR, remissions were of sufficient duration to allow
      patients to receive allogeneic haematopoietic stem cell transplantation. The
      probability of CR/CRp was greater in the 17 patients with B cell precursor ALL
      than in the eight with T-ALL (76% vs. 12%, respectively, P < 0.01). The 18-month
      overall survival probability was 39% and 0% in patients who did or did not
      respond to the treatment, respectively (P < 0.01). These data suggest that the
      clofarabine/cyclophosphamide/etoposide regimen is well tolerated and can induce
      clinical response in a relevant proportion of children with refractory/multiple
      relapsed ALL.

PMID- 19747361
TI  - Plasmodium falciparum infected erythrocytes induce hepcidin (HAMP) mRNA synthesis
      by peripheral blood mononuclear cells.

PMID- 19747362
TI  - A novel splice site mutation c.2278 (-1) G>C in the TMPRSS6 gene causes deletion
      of the substrate binding site of the serine protease resulting in refractory iron
      deficiency anaemia.

PMID- 19747363
TI  - Absence of VOD in paediatric thalassaemic HSCT recipients using defibrotide
      prophylaxis and intravenous Busulphan.
AB  - Hepatic veno-occlusive disease (VOD) is a common complication of haematopoietic
      stem cell transplantation (HSCT), with reported incidences of 5-40% in children.
      Recently, defibrotide (DF) has been successfully used as prophylaxis and
      treatment of VOD. This study reports data on 63 human leucocyte antigen-matched
      HSCT performed in 57 children affected by beta thalassemia at very high risk for
      developing VOD (liver fibrosis, iron overload, hepatitis C virus infections,
      busulphan-based conditioning, methotraexate + ciclosporine). All patients
      received a busulphan-based conditioning regimen, either orally (four HSCT) or
      intravenously (59 HSCT). All patients received oral DF (40 mg/kg per day, final
      dose) as VOD prophylaxis from median day -9 to median day +29. In order to
      overcome the lack of oral paediatric formulations, a galenic formulation was
      administered. DF was well tolerated. Only one patient fulfilled Seattle Criteria
      for VOD diagnosis. This patient had discontinued DF 6 d prior to VOD onset, due
      to high risk of haemorrhage. We concluded that oral defibrotide prophylaxis and
      i.v. busulphan safely abated VOD incidence in high-risk patients who had
      undergone HSCT. A galenic preparation of oral DF also permits this treatment in
      low-weight patients. Costs of DF prophylaxis are acceptable considering the
      reduced incidence of VOD.

PMID- 19747364
TI  - Phospho-STAT5 and phospho-Akt expression in chronic myeloproliferative neoplasms.
AB  - The majority of Myeloproliferative Neoplasms (MPNs) are characterised by
      mutations in genes encoding molecules or receptors involved in cell signalling,
      the most common being the JAK2 V617F mutation. This mutation leads to ligand
      independent activation of downstream signalling pathways by constitutive
      phosphorylation. The signalling pathways affected include the Janus kinase-signal
      transducers and activators of transcription (JAK-STAT) and phosphotidylinositide
      3 kinase (PI3K) pathways, which regulate cell survival and apoptosis
      respectively. Monoclonal antibodies to phospho-STAT5 and phospho-Akt were
      generated and assessed by immunocytochemistry on bone marrow biopsies of MPN
      patients with JAK2 V617F, JAK2 exon 12, MPL exon 10 and KIT D816V mutations. JAK2
      V617F mutation was associated with significantly increased levels of
      phosphorylated STAT5 and Akt in haemopoietic cells, most marked in
      megakaryocytes. In contrast, JAK2 exon 12 and MPL exon 10 mutations did not
      affect the level of phosphorylation. In systemic mastocytosis with KIT D618V
      mutation there was significantly increased expression of phosphorylated STAT5 and
      Akt in neoplastic mast cells although there was no change in the expression in
      other haemopoietic cells. JAK2 V617F is associated with upregulated
      phosphorylation of STAT5 and Akt in megakaryocytes, and to a lesser extent in
      other haemopoietic cells. Immunocytochemistry of bone marrow trephines for these
      phospho-proteins can be used as a supplementary diagnostic test with a high
      negative predictive value.

PMID- 19747365
TI  - Phase II study of the histone deacetylase inhibitor MGCD0103 in patients with
      previously treated chronic lymphocytic leukaemia.
AB  - MGCD0103, an orally available class I histone deacetylase (HDAC) inhibitor, was
      examined for pre-clinical activity in chronic lymphocytic leukaemia (CLL). A
      phase II clinical trial was performed, starting at a dose of 85 mg/d, three times
      per week. Dose escalation to 110 mg or the addition of rituximab was permitted in
      patients without a response after two or more cycles. MGCD0103 demonstrated pre
      clinical activity against CLL cells with a LC(50) (concentration lethal to 50%)
      of 0.23 micromol/l and increased acetylation of the HDAC class I specific target
      histone H3. Twenty-one patients received a median of two cycles of MGCD0103
      (range, 0-12). All patients had previously received fludarabine, 33% were
      fludarabine refractory, and 71% had del(11q22.3) or del(17p13.1). No responses
      according to the National Cancer Institutes 1996 criteria were observed. Three
      patients received 110 mg and four patients received concomitant rituximab, with
      no improvement in response. Grade 3-4 toxicity consisted of infections,
      thrombocytopenia, anaemia, diarrhoea, and fatigue. HDAC inhibition was observed
      in six out of nine patients on day 8. Limited activity was observed with single
      agent MGCD0103 in high risk patients with CLL. Future investigations in CLL
      should focus on broad HDAC inhibition, combination strategies, and approaches to
      diminish constitutional symptoms associated with this class of drugs.

PMID- 19747366
TI  - Association studies of erythroid alpha-spectrin at the tetramerization site.
AB  - The functional roles of residues 21-43 and 55-59 in the alpha-spectrin N-terminal
      region in forming tetramers were determined by the introduction of mutations at
      each of these positions. We measured association affinities for tetramer
      formation (K(d)), which can be used to predict clinical severity, of these
      mutants. A total of nine residues critical for association with beta-spectrin
      were found. The mutations of six of these residues have already been known to
      cause hereditary elliptocytosis or hereditary pyropoikilocytosis. Clinical
      symptoms associated with three mutations of residues 23, 57 and 58 have not yet
      been reported. We suggest that these mutations may also introduce abnormalities
      to erythrocytes.

PMID- 19747367
TI  - The anti-leukaemic activity of novel synthetic naphthoquinones against acute
      myeloid leukaemia: induction of cell death via the triggering of multiple
      signalling pathways.
AB  - Naphthoquinones, such as menadione, display lower toxicity than anthracyclins
      used in cancer chemotherapy. Novel anti-leukaemic compounds comprised of chloro
      amino-phenyl naphthoquinones with substitutions on the benzoic ring were
      developed. Structure-activity relationship studies indicated that the analogue
      with both methyl and amine substitutions (named TW-92) was the most efficient in
      killing leukaemic cells. Treatment of U-937 promonocytic cells with TW-92 induced
      apoptotic or necrotic cell death, dependent on incubation and dose conditions. TW
      92 induced rapid phosphorylation of p38 mitogen-activated protein kinase
      (p38(MAPK)) and of extracellular signal-regulated protein kinases (ERK1/2). The
      generation of apoptosis was preceded by intracellular H(2)O(2) accumulation
      accompanied by glutathione depletion, the former inhibited by di-phenyl-iodonium
      (DPI), an inhibitor of NADPH oxidase. TW-92 induced swelling of isolated rat
      liver mitochondria, indicative of a direct effect on mitochondria. Apoptosis in
      intact cells was accompanied by a decrease in mitochondrial membrane potential,
      cytochrome c release and caspase activation. In addition, the level of Mcl-1, an
      anti-apoptotic regulatory protein, was down-regulated, whereas the expression of
      the pro-apoptotic BAX was elevated. Finally, TW-92 exerted strong pro-apoptotic
      and necrotic effects in primary acute myeloid leukaemia samples when given in
      submicromolar concentrations. Together, these findings demonstrate that TW-92 may
      provide an effective anti-leukaemic strategy.

PMID- 19747368
TI  - Antibody expressing pea seeds as fodder for prevention of gastrointestinal
      parasitic infections in chickens.
AB  - BACKGROUND: Coccidiosis caused by protozoans of genus Eimeria is a chicken
      parasitic disease of great economical importance. Conventional disease control
      strategies depend on vaccination and prophylactic use of anticoccidial drugs.
      Alternative solution to prevent and treat coccidiosis could be provided by
      passive immunization using orally delivered neutralizing antibodies. We
      investigated the possibility to mitigate the parasitic infection by feeding
      poultry with antibody expressing transgenic crop seeds. RESULTS: Using the phage
      display antibody library, we generated a panel of anti-Eimeria scFv antibody
      fragments with high sporozoite-neutralizing activity. These antibodies were
      expressed either transiently in agrobacteria-infiltrated tobacco leaves or stably
      in seeds of transgenic pea plants. Comparison of the scFv antibodies purified
      either from tobacco leaves or from the pea seeds demonstrated no difference in
      their antigen-binding activity and molecular form compositions. Force-feeding
      experiments demonstrated that oral delivery of flour prepared from the transgenic
      pea seeds had higher parasite neutralizing activity in vivo than the purified
      antibody fragments isolated from tobacco. The pea seed content was found to
      protect antibodies against degradation by gastrointestinal proteases (>100-fold
      gain in stability). Ad libitum feeding of chickens demonstrated that the
      transgenic seeds were well consumed and not shunned. Furthermore, feeding poultry
      with shred prepared from the antibody expressing pea seeds led to significant
      mitigation of infection caused both by high and low challenge doses of Eimeria
      oocysts. CONCLUSION: The results suggest that our strategy offers a general
      approach to control parasitic infections in production animals using cost
      effective antibody expression in crop seeds affordable for the animal health
      market.

PMID- 19747369
TI  - Childhood emotional problems and self-perceptions predict weight gain in a
      longitudinal regression model.
AB  - BACKGROUND: Obesity and weight gain are correlated with psychological ill health.
      We predicted that childhood emotional problems and self-perceptions predict
      weight gain into adulthood. METHODS: Data on around 6,500 individuals was taken
      from the 1970 Birth Cohort Study. This sample was a representative sample of
      individuals born in the UK in one week in 1970. Body mass index was measured by a
      trained nurse at the age of 10 years, and self-reported at age 30 years.
      Childhood emotional problems were indexed using the Rutter B scale and self
      report. Self-esteem was measured using the LAWSEQ questionnaire, whilst the
      CARALOC scale was used to measure locus of control. RESULTS: Controlling for
      childhood body mass index, parental body mass index, and social class, childhood
      emotional problems as measured by the Rutter scale predicted weight gain in women
      only (least squares regression N = 3,359; coefficient 0.004; P = 0.032). Using
      the same methods, childhood self-esteem predicted weight gain in both men and
      women (N = 6,526; coefficient 0.023; P < 0.001), although the effect was stronger
      in women. An external locus of control predicted weight gain in both men and
      women (N = 6,522; coefficient 0.022; P < 0.001). CONCLUSION: Emotional problems,
      low self-esteem and an external locus of control in childhood predict weight gain
      into adulthood. This has important clinical implications as it highlights a
      direction for early intervention strategies that may contribute to efforts to
      combat the current obesity epidemic.

PMID- 19747371
TI  - A global approach to the management of EMR (electronic medical records) of
      patients with HIV/AIDS in sub-Saharan Africa: the experience of DREAM software.
AB  - BACKGROUND: The DREAM Project operates within the framework of the national
      health systems of several sub-Saharan African countries and aims to introduce the
      essential components of an integrated strategy for the prevention and treatment
      of HIV/AIDS. The project is intended to serve as a model for a wide-ranging scale
      up in the response to the epidemic. This paper aims to show DREAM's challenges
      and the solutions adopted. One of the solutions is the efficient management of
      the clinical data regarding the treatment of the patients and epidemiological
      analyses. METHODS: Specific software for the management of the patients' EMR has
      been created within the DREAM programme in order to deal with the challenges
      deriving from the context in which DREAM operates. Setting up a computer
      infrastructure in health centres, providing a power supply, as well as managing
      the data and the project resources efficiently and reliably, are some of the
      questions that have been analysed in this study. RESULTS: Over the years this
      software has proved that it is able to respond to the need for efficient
      management of the clinical data and organization of the health centres. Today it
      is used in 10 countries in sub-Saharan Africa by thousands of professionals and
      by now it has reached its fourth version. The medical files of over 73,000
      assisted patients are managed by this software and the data collected with it
      have become essential for the epidemiological research that is carried out to
      improve the effectiveness of the therapy. CONCLUSION: Sub-Saharan Africa is the
      region hardest hit by HIV and AIDS in the world. However, the resources and
      responses adopted so far, to confront the epidemic, have at times been rather
      minimalist. The DREAM project has faced the battle against the epidemic by
      equipping itself with qualitative standards comparable to Western ones. The
      experience of DREAM has revealed that it is indeed possible to guarantee levels
      of excellence in developing countries, also in the sphere of ICT (Information and
      Communication Technology), thus making the intervention even more effective and
      contributing to bridging the digital divide.

PMID- 19747370
TI  - Epigenetic inheritance of an inducibly nucleosome-depleted promoter and its
      associated transcriptional state in the apparent absence of transcriptional
      activators.
AB  - BACKGROUND: Dynamic changes to the chromatin structure play a critical role in
      transcriptional regulation. This is exemplified by the Spt6-mediated histone
      deposition on to histone-depleted promoters that results in displacement of the
      general transcriptional machinery during transcriptional repression. RESULTS:
      Using the yeast PHO5 promoter as a model, we have previously shown that blocking
      Spt6-mediated histone deposition on to the promoter leads to persistent
      transcription in the apparent absence of transcriptional activators in vivo. We
      now show that the nucleosome-depleted PHO5 promoter and its associated
      transcriptionally active state can be inherited through DNA replication even in
      the absence of transcriptional activators. Transcriptional reinitiation from the
      nucleosome-depleted PHO5 promoter in the apparent absence of activators in vivo
      does not require Mediator. Notably, the epigenetic inheritance of the nucleosome
      depleted PHO5 promoter through DNA replication does not require ongoing
      transcription. CONCLUSION: Our results suggest that there may be a memory or an
      epigenetic mark on the nucleosome-depleted PHO5 promoter that is independent of
      the transcription apparatus and maintains the promoter in a nucleosome-depleted
      state through DNA replication.

PMID- 19747373
TI  - Tiny but complex - interactive 3D visualization of the interstitial acochlidian
      gastropod Pseudunela cornuta (Challis, 1970).
AB  - BACKGROUND: Mesopsammic acochlidians are small, and organ complexity may be
      strongly reduced (regressive evolution by progenesis), especially in
      microhedylacean species. The marine interstitial hedylopsacean Pseudunela cornuta
      (Challis, 1970), however, was suggested as having a complex reproductive system
      resembling that of much larger, limnic and benthic species. The present study
      aims to reconstruct the detailed anatomy and true complexity of P. cornuta from
      serial, semithin histological sections by using modern computer-based 3D
      visualization with Amira software, and to explain it in an evolutionary context.
      RESULTS: Our results demonstrate considerable discordance with the original
      species description, which was based solely on paraffin sections. Here, we show
      that the nervous system of P. cornuta has paired rhinophoral, optic and gastro
      oesophageal ganglia, three distinct ganglia on the visceral nerve cord, and a
      putative osphradial ganglion, while anterior accessory ganglia are absent. The
      presence of an anal genital cloaca is clearly rejected and the anus, nephropore
      and gonopore open separately to the exterior; the circulatory and excretory
      systems are well-differentiated, including a two-chambered heart and a complex
      kidney with a long, looped nephroduct; the special androdiaulic reproductive
      system shows two allosperm receptacles, three nidamental glands, a cavity with
      unknown function, as well as highly complex anterior copulatory organs with two
      separate glandular and impregnatory systems including a penial stylet that
      measures approximately a third of the whole length of the preserved specimen.
      CONCLUSION: In spite of its small body size, the interstitial hermaphroditic P.
      cornuta shows high complexity regarding all major organ systems; the excretory
      system is as differentiated as in species of the sister clade, the limnic and
      much larger Acochlidiidae, and the reproductive system is by far the most
      elaborated one ever observed in a mesopsammic gastropod, though functionally not
      yet fully understood. Such organ complexity as shown herein by interactive 3D
      visualization is not plesiomorphically maintained from a larger, benthic
      ancestor, but newly evolved within small marine hedylopsacean ancestors of P.
      cornuta. The common picture of general organ regression within mesopsammic
      acochlidians thus is valid for microhedylacean species only.

PMID- 19747372
TI  - Changes in the central component of the hypothalamus-pituitary-thyroid axis in a
      rabbit model of prolonged critical illness.
AB  - INTRODUCTION: Prolonged critically ill patients reveal low circulating thyroid
      hormone levels without a rise in thyroid stimulating hormone (TSH). This
      condition is labeled "low 3,5,3'-tri-iodothyronine (T3) syndrome" or
      "nonthyroidal illness syndrome (NTI)" or "euthyroid sick syndrome". Despite the
      low circulating and peripheral tissue thyroid hormone levels, thyrotropin
      releasing hormone (TRH) expression in the hypothalamus is reduced and it remains
      unclear which mechanism is responsible. We set out to study whether increased
      hypothalamic T3 availability could reflect local thyrotoxicosis and explain
      feedback inhibition-induced suppression of the TRH gene in the context of the low
      T3 syndrome in prolonged critical illness. METHODS: Healthy rabbits were compared
      with prolonged critically ill, parenterally fed animals. We visualized TRH mRNA
      in the hypothalamus by in situ-hybridization and measured mRNA levels for the
      type II iodothyronine diodinase (D2), the thyroid hormone transporters
      monocarboxylate transporter (MCT) 8, MCT10 and organic anion co-transporting
      polypeptide 1C1 (OATP1C1) and the thyroid hormone receptors alpha (TRalpha) and
      beta (TRbeta) in the hypothalamus. We also measured the activity of the D2 and
      type III iodothyronine deiodinase (D3) enzymes. RESULTS: In the hypothalamus of
      prolonged critically ill rabbits with low circulating T3 and TSH, we observed
      decreased TRH mRNA, increased D2 mRNA and increased MCT10 and OATP1C1 mRNA while
      MCT8 gene expression was unaltered as compared with healthy controls. This
      coincided with low hypothalamic thyroxine (T4) and low-normal T3 concentrations,
      without a change at the thyroid hormone receptor level. CONCLUSIONS: Although
      expression of D2 and of the thyroid hormone transporters MCT10 and OATP1C1 were
      increased in the hypothalamus of prolonged critical ill animals, hypothalamic T4
      and T3 content or thyroid hormone receptor expression were not elevated. Hence,
      decreased TRH gene expression, and hereby low TSH and T3 during prolonged
      critical illness, is not exclusively brought about by hypothalamic
      thyrotoxicosis, and infer other TRH suppressing factors to play a role.

PMID- 19747374
TI  - Identification of a region required for TSC1 stability by functional analysis of
      TSC1 missense mutations found in individuals with tuberous sclerosis complex.
AB  - BACKGROUND: Tuberous sclerosis complex (TSC) is an autosomal dominant disorder
      characterised by the development of hamartomas in a variety of organs and
      tissues. The disease is caused by mutations in either the TSC1 gene on chromosome
      9q34, or the TSC2 gene on chromosome 16p13.3. The TSC1 and TSC2 gene products,
      TSC1 and TSC2, form a protein complex that inhibits signal transduction to the
      downstream effectors of the mammalian target of rapamycin (mTOR). Recently it has
      been shown that missense mutations to the TSC1 gene can cause TSC. METHODS: We
      have used in vitro biochemical assays to investigate the effects on TSC1 function
      of TSC1 missense variants submitted to the Leiden Open Variation Database.
      RESULTS: We identified specific substitutions between amino acids 50 and 190 in
      the N-terminal region of TSC1 that result in reduced steady state levels of the
      protein and lead to increased mTOR signalling. CONCLUSION: Our results suggest
      that amino acid residues within the N-terminal region of TSC1 are important for
      TSC1 function and for maintaining the activity of the TSC1-TSC2 complex.

PMID- 19747375
TI  - Monodispersity of recombinant Cre recombinase correlates with its effectiveness
      in vivo.
AB  - BACKGROUND: Cre recombinase is a common reagent used for the in vivo on/off
      switching of the expression of target genes flanked by loxP sites. In particular,
      recombinant TAT-Cre fusion constructs purified from bacteria have been used to
      promote the cell uptake of the enzyme. However, the recovery of active TAT-Cre
      remains a demanding process and its specific activity varies significantly among
      batches, making difficult data comparison. RESULTS: We noticed a strong
      correlation between recombinase activity and enzyme monodispersity. The existence
      of such correlation enabled us to indirectly monitor the TAT-Cre recombinase
      activity during the multi-step purification process by measuring its
      monodispersity, a parameter detectable by means of a spectrofluorimetric assay
      that allows the calculation of the Aggregation Index (AI) in an easy and rapid
      way. AI values were recorded after each purification passage to identify the
      critical steps and to choose optimal alternatives for chromatographic conditions,
      desalting procedures, and protocols for bacterial endotoxin removal. Furthermore,
      the effect of metal ions and temperature on TAT-Cre aggregation and inactivation
      was characterized in vitro. Finally, we optimized the enzyme delivery protocol in
      vivo by following the accumulation tuning of the reporter protein beta-catenin.
      CONCLUSION: A rational purification protocol for TAT-Cre has been developed by
      choosing the options that minimize the enzyme aggregation. Our data suggest that
      AI measurement should support the optimization of any protocol aiming at the
      recovery of monodispersed protein.

PMID- 19747376
TI  - Planning for translational research in genomics.
AB  - Translation of research findings into clinical practice is an important aspect of
      medical progress. Even for the early stages of genomics, research aiming to
      deepen understandings of underlying mechanisms of disease, questions about the
      ways in which such research ultimately can be useful in medical treatment and
      public health are of key importance. Whilst some research data may not apparently
      lend themselves to immediate clinical benefit, being aware of the issues
      surrounding translation at an early stage can enhance the delivery of the
      research to the clinic if a medical application is later found. When simple steps
      are taken during initial project planning, the pathways towards the translation
      of genomic research findings can be managed to optimize long-term benefits to
      health. This piece discusses the key areas of collaboration agreements,
      distribution of revenues and recruitment and sample collection that are
      increasingly important to successful translational research in genomics.

PMID- 19747377
TI  - Genotyping of Streptococcus agalactiae (group B streptococci) isolated from
      vaginal and rectal swabs of women at 35-37 weeks of pregnancy.
AB  - BACKGROUND: Group B streptococci (GBS), or Streptococcus agalactiae, are the
      leading bacterial cause of meningitis and bacterial sepsis in newborns. Here we
      compared different culture media for GBS detection and we compared the occurrence
      of different genotypes and serotypes of GBS isolates from the vagina and rectum.
      METHODS: Streptococcus agalactiae was cultured separately from both rectum and
      vagina, for a total of 150 pregnant women, i) directly onto Columbia CNA agar, or
      indirectly onto ii) Granada agar resp. iii) Columbia CNA agar, after overnight
      incubation in Lim broth. RESULTS: Thirty six women (24%) were colonized by GBS.
      Of these, 19 harbored GBS in both rectum and vagina, 9 only in the vagina and 8
      exclusively in the rectum. The combination of Lim broth and subculture on Granada
      agar was the only culture method that detected all GBS positive women. Using RAPD
      analysis, a total of 66 genotypes could be established among the 118 isolates
      from 32 women for which fingerprinting was carried out. Up to 4 different
      genotypes in total (rectal + vaginal) were found for 4 women, one woman carried 3
      different genotypes vaginally and 14 women carried two 2 different genotypes
      vaginally. Only two subjects were found to carry strains with the same genotype,
      although the serotype of both of these strains was different.Eighteen of the 19
      subjects with GBS at both sites had at least one vaginal and one rectal isolate
      with the same genotype.We report the presence of two to four different genotypes
      in 22 (61%) of the 36 GBS positive women and the presence of identical genotypes
      in both sites for all women but one. CONCLUSION: The combination of Lim broth and
      subculture on Granada medium provide high sensitivity for GBS detection from
      vaginal and rectal swabs from pregnant women. We established a higher genotypic
      diversity per individual than other studies, with up to four different genotypes
      among a maximum of 6 isolates per individual picked. Still, 18 of the 19 women
      with GBS from both rectum and vagina had at least one isolate from each sampling
      site with the same genotype.

PMID- 19747378
TI  - Involvement of insulin-degrading enzyme in the clearance of beta-amyloid at the
      blood-CSF barrier: Consequences of lead exposure.
AB  - BACKGROUND: Alzheimer's disease (AD) is characterized by the deposition of beta
      amyloid (Abeta) peptides in the brain extracellular matrix, resulting in
      pathological changes and neurobehavioral deficits. Previous work from this
      laboratory demonstrated that the choroid plexus (CP) possesses the capacity to
      remove Abeta from the cerebrospinal fluid (CSF), and exposure to lead (Pb)
      compromises this function. Since metalloendopeptidase insulin-degrading enzyme
      (IDE), has been implicated in the metabolism of Abeta, we sought to investigate
      whether accumulation of Abeta following Pb exposure was due to the effect of Pb
      on IDE. METHODS: Rats were injected with a single dose of Pb acetate or an
      equivalent concentration of Na-acetate; CP tissues were processed to detect the
      location of IDE by immunohistochemistry. For in vitro studies, choroidal
      epithelial Z310 cells were treated with Pb for 24 h in the presence or absence of
      a known IDE inhibitor, N-ethylmaleimide (NEM) to assess IDE enzymatic activity
      and subsequent metabolic clearance of Abeta. Additionally, the expression of IDE
      mRNA and protein were determined using real time PCR and western blots
      respectively. RESULTS: Immunohistochemistry and confocal imaging revealed the
      presence of IDE towards the apical surface of the CP tissue with no visible
      alteration in either its intensity or location following Pb exposure. There was
      no significant difference in the expressions of either IDE mRNA or protein
      following Pb exposure compared to controls either in CP tissues or in Z310 cells.
      However, our findings revealed a significant decrease in the IDE activity
      following Pb exposure; this inhibition was similar to that seen in the cells
      treated with NEM alone. Interestingly, treatment with Pb or NEM alone
      significantly increased the levels of intracellular Abeta, and a greater
      accumulation of Abeta was seen when the cells were exposed to a combination of
      both. CONCLUSION: These data suggest that Pb exposure inhibits IDE activity but
      does not affect its expression in the CP. This, in turn, leads to a disrupted
      metabolism of Abeta resulting in its accumulation at the blood-CSF barrier.

PMID- 19747379
TI  - Genome-wide expression profiling of in vivo-derived bloodstream parasite stages
      and dynamic analysis of mRNA alterations during synchronous differentiation in
      Trypanosoma brucei.
AB  - BACKGROUND: Trypanosomes undergo extensive developmental changes during their
      complex life cycle. Crucial among these is the transition between slender and
      stumpy bloodstream forms and, thereafter, the differentiation from stumpy to
      tsetse-midgut procyclic forms. These developmental events are highly regulated,
      temporally reproducible and accompanied by expression changes mediated almost
      exclusively at the post-transcriptional level. RESULTS: In this study we have
      examined, by whole-genome microarray analysis, the mRNA abundance of genes in
      slender and stumpy forms of T.brucei AnTat1.1 cells, and also during their
      synchronous differentiation to procyclic forms. In total, five biological
      replicates representing the differentiation of matched parasite populations
      derived from five individual mouse infections were assayed, with RNAs being
      derived at key biological time points during the time course of their synchronous
      differentiation to procyclic forms. Importantly, the biological context of these
      mRNA profiles was established by assaying the coincident cellular events in each
      population (surface antigen exchange, morphological restructuring, cell cycle re
      entry), thereby linking the observed gene expression changes to the well
      established framework of trypanosome differentiation. CONCLUSION: Using stringent
      statistical analysis and validation of the derived profiles against
      experimentally-predicted gene expression and phenotypic changes, we have
      established the profile of regulated gene expression during these important life
      cycle transitions. The highly synchronous nature of differentiation between
      stumpy and procyclic forms also means that these studies of mRNA profiles are
      directly relevant to the changes in mRNA abundance within individual cells during
      this well-characterised developmental transition.

PMID- 19747380
TI  - Improving mental and neurological health research in Latin America: a qualitative
      study.
AB  - BACKGROUND: Research evidence is essential to inform policies, interventions and
      programs, and yet research activities in mental and neurological (MN) health have
      been largely neglected, particularly in low- and middle-income countries. Many
      challenges have been identified in the production and utilization of research
      evidence in Latin American countries, and more work is needed to overcome this
      disadvantageous situation. This study aims to address the situation by
      identifying initiatives that could improve MN health research activities and
      implementation of their results in the Latin American region. METHODS: Thirty
      four MN health actors from 13 Latin American countries were interviewed as part
      of an initiative by the Global Forum for Health Research and the World Health
      Organization to explore the status of MN health research in low- and middle
      income countries in Africa, Asia and Latin-America. RESULTS: A variety of
      recommendations to increase MN health research activities and implementation of
      their results emerged in the interviews. These included increasing skilled human
      resources in MN health interventions and research, fostering greater
      participation of stakeholders in the generation of research topics and projects,
      and engendering the interest of national and international institutions in
      important MN health issues and research methodologies. In the view of most
      participants, government agencies should strive to have research results inform
      the decision-making process in which they are involved. Thus these agencies would
      play a key role in facilitating and funding research. Participants also pointed
      to the importance of academic recognition and financial rewards in attracting
      professionals to primary and translational research in MN health. In addition,
      they suggested that institutions should create intramural resources to provide
      researchers with technical support in designing, carrying out and disseminating
      research, including resources to improve scientific writing skills. CONCLUSION:
      Fulfillment of these recommendations would increase research production in MN
      health in Latin American countries. This, in turn, will raise the profile of
      these health problems, and consequently will underscore the need of continued
      high-quality and relevant research, thus fostering a virtuous cycle in the
      decision-making process to improve MN health care.

PMID- 19747381
TI  - Evolutionary constraints permeate large metabolic networks.
AB  - BACKGROUND: Metabolic networks show great evolutionary plasticity, because they
      can differ substantially even among closely related prokaryotes. Any one
      metabolic network can also effectively compensate for the blockage of individual
      reactions by rerouting metabolic flux through other pathways. These observations,
      together with the continual discovery of new microbial metabolic pathways and
      enzymes, raise the possibility that metabolic networks are only weakly
      constrained in changing their complement of enzymatic reactions. RESULTS: To ask
      whether this is the case, I characterized pairwise and higher-order associations
      in the co-occurrence of genes encoding metabolic enzymes in more than 200
      completely sequenced representatives of prokaryotic genera. The majority of
      reactions show constrained evolution. Specifically, genes encoding most reactions
      tend to co-occur with genes encoding other reaction(s). Constrained reaction
      pairs occur in small sets whose number is substantially greater than expected by
      chance alone. Most such sets are associated with single biochemical pathways. The
      respective genes are not always tightly linked, which renders horizontal co
      transfer of constrained reaction sets an unlikely sole cause for these patterns
      of association. CONCLUSION: Even a limited number of available genomes suffices
      to show that metabolic network evolution is highly constrained by reaction
      combinations that are favored by natural selection. With increasing numbers of
      completely sequenced genomes, an evolutionary constraint-based approach may
      enable a detailed characterization of co-evolving metabolic modules.

PMID- 19747382
TI  - Nested-multiplex PCR detection of Orthopoxvirus and Parapoxvirus directly from
      exanthematic clinical samples.
AB  - BACKGROUND: Orthopoxvirus (OPV) and Parapoxvirus (PPV) have been associated with
      worldwide exanthematic outbreaks. Some species of these genera are able to infect
      humans and domestic animals, causing serious economic losses and public health
      impact. Rapid, useful and highly specific methods are required to detect and
      epidemiologically monitor such poxviruses. In the present paper, we describe the
      development of a nested-multiplex PCR method for the simultaneous detection of
      OPV and PPV species directly from exanthematic lesions, with no previous viral
      isolation or DNA extraction. METHODS AND RESULTS: The OPV/PPV nested-multiplex
      PCR was developed based on the evaluation and combination of published primer
      sets, and was applied to the detection of the target pathogens. The method showed
      high sensitivity, and the specificity was confirmed by amplicon sequencing.
      Exanthematic lesion samples collected during bovine vaccinia or contagious
      ecthyma outbreaks were submitted to OPV/PPV nested-multiplex PCR and confirmed
      its applicability. CONCLUSION: These results suggest that the presented multiplex
      PCR provides a highly robust and sensitive method to detect OPV and PPV directly
      from clinical samples. The method can be used for viral identification and
      monitoring, especially in areas where OPV and PPV co-circulate.

PMID- 19747383
TI  - Intensive care adult patients with severe respiratory failure caused by Influenza
      A (H1N1)v in Spain.
AB  - INTRODUCTION: Patients with influenza A (H1N1)v infection have developed rapidly
      progressive lower respiratory tract disease resulting in respiratory failure. We
      describe the clinical and epidemiologic characteristics of the first 32 persons
      reported to be admitted to the intensive care unit (ICU) due to influenza A
      (H1N1)v infection in Spain. METHODS: We used medical chart reviews to collect
      data on ICU adult patients reported in a standardized form. Influenza A (H1N1)v
      infection was confirmed in specimens using real-time reverse transcriptase
      polymerase-chain-reaction (RT PCR) assay. RESULTS: Illness onset of the 32
      patients occurred between 23 June and 31 July, 2009. The median age was 36 years
      (IQR = 31 - 52). Ten (31.2%) were obese, 2 (6.3%) pregnant and 16 (50%) had pre
      existing medical complications. Twenty-nine (90.6%) had primary viral
      pneumonitis, 2 (6.3%) exacerbation of structural respiratory disease and 1 (3.1%)
      secondary bacterial pneumonia. Twenty-four patients (75.0%) developed multiorgan
      dysfunction, 7 (21.9%) received renal replacement techniques and 24 (75.0%)
      required mechanical ventilation. Six patients died within 28 days, with two
      additional late deaths. Oseltamivir administration delay ranged from 2 to 8 days
      after illness onset, 31.2% received high-dose (300 mg/day), and treatment
      duration ranged from 5 to 10 days (mean 8.0 +/- 3.3). CONCLUSIONS: Over a 5-week
      period, influenza A (H1N1)v infection led to ICU admission in 32 adult patients,
      with frequently observed severe hypoxemia and a relatively high case-fatality
      rate. Clinicians should be aware of pulmonary complications of influenza A
      (H1N1)v infection, particularly in pregnant and young obese but previously
      healthy persons.

PMID- 19747384
TI  - Quality of life in caregivers of patients with schizophrenia: a literature
      review.
AB  - BACKGROUND: A couple of decades ago, hospitals or psychiatric institutions were
      in charge of caring for patients with schizophrenia; however, nowadays this role
      is performed by one or more patient's relatives. Evidence shows that informal
      caregivers experience negative changes in their quality of life (QOL). The aim of
      this study is to review the main factors associated with the QOL of caregivers of
      people with schizophrenia. METHODS: A search through databases from journals
      published last decade between 1998 and 2008 was performed. In accordance with the
      inclusion criteria, titles and abstracts of citations obtained from the search
      were examined independently by two authors and irrelevant articles discarded. The
      full text of those studies considered relevant by either reviewer were obtained
      and assessed independently. Where differences of opinion rose they were resolved
      by discussion. Out of the 258 references, 37 were included in the review. Studies
      which assessed factors associated with caregivers of people with schizophrenia's
      quality of life were included and the information summarized. RESULTS: Evidence
      suggest that physical, emotional and economic distress affect negatively
      caregiver's QOL as a result of a number of unfulfilled needs such as, restoration
      of patient functioning in family and social roles, economic burden, lack of spare
      time, among other factors. CONCLUSION: Decreased QOL may be associated with
      caregivers' burden, lack of social support, course of the disease and family
      relationships problems. In addition, in developing countries, QOL is affected by
      caregivers' economic burden. High quality research is needed in order to identify
      factors associated with QOL over time and testing the efficacy of interventions
      aiming to improve QOL in caregivers of patients with schizophrenia.

PMID- 19747385
TI  - Effects of alpha-linolenic acid vs. docosahexaenoic acid supply on the
      distribution of fatty acids among the rat cardiac subcellular membranes after a
      short- or long-term dietary exposure.

PMID- 19747386
TI  - A new set of ESTs and cDNA clones from full-length and normalized libraries for
      gene discovery and functional characterization in citrus.
AB  - BACKGROUND: Interpretation of ever-increasing raw sequence information generated
      by modern genome sequencing technologies faces multiple challenges, such as gene
      function analysis and genome annotation. Indeed, nearly 40% of genes in plants
      encode proteins of unknown function. Functional characterization of these genes
      is one of the main challenges in modern biology. In this regard, the availability
      of full-length cDNA clones may fill in the gap created between sequence
      information and biological knowledge. Full-length cDNA clones facilitate
      functional analysis of the corresponding genes enabling manipulation of their
      expression in heterologous systems and the generation of a variety of tagged
      versions of the native protein. In addition, the development of full-length cDNA
      sequences has the power to improve the quality of genome annotation. RESULTS: We
      developed an integrated method to generate a new normalized EST collection
      enriched in full-length and rare transcripts of different citrus species from
      multiple tissues and developmental stages. We constructed a total of 15 cDNA
      libraries, from which we isolated 10,898 high-quality ESTs representing 6142
      different genes. Percentages of redundancy and proportion of full-length clones
      range from 8 to 33, and 67 to 85, respectively, indicating good efficiency of the
      approach employed. The new EST collection adds 2113 new citrus ESTs, representing
      1831 unigenes, to the collection of citrus genes available in the public
      databases. To facilitate functional analysis, cDNAs were introduced in a Gateway
      based cloning vector for high-throughput functional analysis of genes in planta.
      Herein, we describe the technical methods used in the library construction,
      sequence analysis of clones and the overexpression of CitrSEP, a citrus homolog
      to the Arabidopsis SEP3 gene, in Arabidopsis as an example of a practical
      application of the engineered Gateway vector for functional analysis. CONCLUSION:
      The new EST collection denotes an important step towards the identification of
      all genes in the citrus genome. Furthermore, public availability of the cDNA
      clones generated in this study, and not only their sequence, enables testing of
      the biological function of the genes represented in the collection. Expression of
      the citrus SEP3 homologue, CitrSEP, in Arabidopsis results in early flowering,
      along with other phenotypes resembling the over-expression of the Arabidopsis
      SEPALLATA genes. Our findings suggest that the members of the SEP gene family
      play similar roles in these quite distant plant species.

PMID- 19747387
TI  - Daptomycin for treatment of methicillin-resistant Staphylococcus epidermidis
      saphenectomy wound infection after coronary artery bypass graft operation (CABG):
      a case report.
AB  - We report a case of successful treatment of postoperative saphenectomy wound
      infection of the upper left leg with the antibiotic drug Daptomycin.

PMID- 19747388
TI  - De novo genome sequence assembly of a filamentous fungus using Sanger, 454 and
      Illumina sequence data.
AB  - Sequencing-by-synthesis technologies can reduce the cost of generating de novo
      genome assemblies. We report a method for assembling draft genome sequences of
      eukaryotic organisms that integrates sequence information from different sources,
      and demonstrate its effectiveness by assembling an approximately 32.5 Mb draft
      genome sequence for the forest pathogen Grosmannia clavigera, an ascomycete
      fungus. We also developed a method for assessing draft assemblies using Illumina
      paired end read data and demonstrate how we are using it to guide future sequence
      finishing. Our results demonstrate that eukaryotic genome sequences can be
      accurately assembled by combining Illumina, 454 and Sanger sequence data.

PMID- 19747389
TI  - Generalist dinoflagellate endosymbionts and host genotype diversity detected from
      mesophotic (67-100 m depths) coral Leptoseris.
AB  - BACKGROUND: Mesophotic corals (light-dependent corals in the deepest half of the
      photic zone at depths of 30-150 m) provide a unique opportunity to study the
      limits of the interactions between corals and endosymbiotic dinoflagellates in
      the genus Symbiodinium. We sampled Leptoseris spp. in Hawaii via manned
      submersibles across a depth range of 67-100 m. Both the host and Symbiodinium
      communities were genotyped, using a non-coding region of the mitochondrial ND5
      intron (NAD5) and the nuclear ribosomal internal transcribed spacer region 2
      (ITS2), respectively. RESULTS: Coral colonies harbored endosymbiotic communities
      dominated by previously identified shallow water Symbiodinium ITS2 types (C1_
      AF333515, C1c_ AY239364, C27_ AY239379, and C1b_ AY239363) and exhibited genetic
      variability at mitochondrial NAD5. CONCLUSION: This is one of the first studies
      to examine genetic diversity in corals and their endosymbiotic dinoflagellates
      sampled at the limits of the depth and light gradients for hermatypic corals. The
      results reveal that these corals associate with generalist endosymbiont types
      commonly found in shallow water corals and implies that the composition of the
      Symbiodinium community (based on ITS2) alone is not responsible for the dominance
      and broad depth distribution of Leptoseris spp. The level of genetic diversity
      detected in the coral NAD5 suggests that there is undescribed taxonomic diversity
      in the genus Leptoseris from Hawaii.

PMID- 19747390
TI  - BRICHOS - a superfamily of multidomain proteins with diverse functions.
AB  - BACKGROUND: The BRICHOS domain has been found in 8 protein families with a wide
      range of functions and a variety of disease associations, such as respiratory
      distress syndrome, dementia and cancer. The domain itself is thought to have a
      chaperone function, and indeed three of the families are associated with amyloid
      formation, but its structure and many of its functional properties are still
      unknown. FINDINGS: The proteins in the BRICHOS superfamily have four regions with
      distinct properties. We have analysed the BRICHOS proteins focusing on sequence
      conservation, amino acid residue properties, native disorder and secondary
      structure predictions. Residue conservation shows large variations between the
      regions, and the spread of residue conservation between different families can
      vary greatly within the regions. The secondary structure predictions for the
      BRICHOS proteins show remarkable coherence even where sequence conservation is
      low, and there seems to be little native disorder. CONCLUSIONS: The greatly
      variant rates of conservation indicates different functional constraints among
      the regions and among the families. We present three previously unknown BRICHOS
      families; group A, which may be ancestral to the ITM2 families; group B, which is
      a close relative to the gastrokine families, and group C, which appears to be a
      truly novel, disjoint BRICHOS family. The C-terminal region of group C has nearly
      identical sequences in all species ranging from fish to man and is seemingly
      unique to this family, indicating critical functional or structural properties.

PMID- 19747391
TI  - Gene-based microsatellites for cassava (Manihot esculenta Crantz): prevalence,
      polymorphisms, and cross-taxa utility.
AB  - BACKGROUND: Cassava (Manihot esculenta Crantz), a starchy root crop grown in
      tropical and subtropical climates, is the sixth most important crop in the world
      after wheat, rice, maize, potato and barley. The repertoire of simple sequence
      repeat (SSR) markers for cassava is limited and warrants a need for a larger
      number of polymorphic SSRs for germplasm characterization and breeding
      applications. RESULTS: A total of 846 putative microsatellites were identified in
      silico from an 8,577 cassava unigene set with an average density of one SSR every
      7 kb. One hundred and ninety-two candidate SSRs were screened for polymorphism
      among a panel of cassava cultivars from Africa, Latin America and Asia, four wild
      Manihot species as well as two other important taxa in the Euphorbiaceae, leafy
      spurge (Euphorbia esula) and castor bean (Ricinus communis). Of 168 markers with
      clean amplification products, 124 (73.8%) displayed polymorphism based on high
      resolution agarose gels. Of 85 EST-SSR markers screened, 80 (94.1%) amplified
      alleles from one or more wild species (M epruinosa, M glaziovii, M brachyandra, M
      tripartita) whereas 13 (15.3%) amplified alleles from castor bean and 9 (10.6%)
      amplified alleles from leafy spurge; hence nearly all markers were transferable
      to wild relatives of M esculenta while only a fraction was transferable to the
      more distantly related taxa. In a subset of 20 EST-SSRs assessed by fluorescence
      based genotyping the number of alleles per locus ranged from 2 to 10 with an
      average of 4.55 per locus. These markers had a polymorphism information content
      (PIC) from 0.19 to 0.75 with an average value of 0.55 and showed genetic
      relationships consistent with existing information on these genotypes.
      CONCLUSION: A set of 124 new, unique polymorphic EST-SSRs was developed and
      characterized which extends the repertoire of SSR markers for cultivated cassava
      and its wild relatives. The markers show high PIC values and therefore will be
      useful for cultivar identification, taxonomic studies, and genetic mapping. The
      study further shows that mining ESTs is a highly efficient strategy for
      polymorphism detection within the cultivated cassava gene pool.

PMID- 19747392
TI  - Genetic variation at hair length candidate genes in elephants and the extinct
      woolly mammoth.
AB  - BACKGROUND: Like humans, the living elephants are unusual among mammals in being
      sparsely covered with hair. Relative to extant elephants, the extinct woolly
      mammoth, Mammuthus primigenius, had a dense hair cover and extremely long hair,
      which likely were adaptations to its subarctic habitat. The fibroblast growth
      factor 5 (FGF5) gene affects hair length in a diverse set of mammalian species.
      Mutations in FGF5 lead to recessive long hair phenotypes in mice, dogs, and cats;
      and the gene has been implicated in hair length variation in rabbits. Thus, FGF5
      represents a leading candidate gene for the phenotypic differences in hair length
      notable between extant elephants and the woolly mammoth. We therefore sequenced
      the three exons (except for the 3' UTR) and a portion of the promoter of FGF5
      from the living elephantid species (Asian, African savanna and African forest
      elephants) and, using protocols for ancient DNA, from a woolly mammoth. RESULTS:
      Between the extant elephants and the mammoth, two single base substitutions were
      observed in FGF5, neither of which alters the amino acid sequence. Modeling of
      the protein structure suggests that the elephantid proteins fold similarly to the
      human FGF5 protein. Bioinformatics analyses and DNA sequencing of another locus
      that has been implicated in hair cover in humans, type I hair keratin pseudogene
      (KRTHAP1), also yielded negative results. Interestingly, KRTHAP1 is a pseudogene
      in elephantids as in humans (although fully functional in non-human primates).
      CONCLUSION: The data suggest that the coding sequence of the FGF5 gene is not the
      critical determinant of hair length differences among elephantids. The results
      are discussed in the context of hairlessness among mammals and in terms of the
      potential impact of large body size, subarctic conditions, and an aquatic
      ancestor on hair cover in the Proboscidea.

PMID- 19747393
TI  - Improving power in genetic-association studies via wavelet transformation.
AB  - BACKGROUND: A key to increasing the power of multilocus association tests is to
      reduce the number of degrees of freedom by suppressing noise from data. One of
      the difficulties is to decide how much noise to suppress. An often overlooked
      problem is that commonly used association tests based on genotype data cannot
      utilize the genetic information contained in spatial ordering of SNPs (see proof
      in the Appendix), which may prevent them from achieving higher power. RESULTS: We
      develop a score test based on wavelet transform with empirical Bayesian
      thresholding. Extensive simulation studies are carried out under various LD
      structures as well as using HapMap data from many different chromosomes for both
      qualitative and quantitative traits. Simulation results show that the proposed
      test automatically adjusts the level of noise suppression according to LD
      structures, and it is able to consistently achieve higher or similar powers than
      many commonly used association tests including the principle component regression
      method (PCReg). CONCLUSION: The wavelet-based score test automatically suppresses
      the right amount of noise and uses the information contained in spatial ordering
      of SNPs to achieve higher power.

PMID- 19747394
TI  - Gene expression meta-analysis supports existence of molecular apocrine breast
      cancer with a role for androgen receptor and implies interactions with ErbB
      family.
AB  - BACKGROUND: Pathway discovery from gene expression data can provide important
      insight into the relationship between signaling networks and cancer biology.
      Oncogenic signaling pathways are commonly inferred by comparison with signatures
      derived from cell lines. We use the Molecular Apocrine subtype of breast cancer
      to demonstrate our ability to infer pathways directly from patients' gene
      expression data with pattern analysis algorithms. METHODS: We combine data from
      two studies that propose the existence of the Molecular Apocrine phenotype. We
      use quantile normalization and XPN to minimize institutional bias in the data. We
      use hierarchical clustering, principal components analysis, and comparison of
      gene signatures derived from Significance Analysis of Microarrays to establish
      the existence of the Molecular Apocrine subtype and the equivalence of its
      molecular phenotype across both institutions. Statistical significance was
      computed using the Fasano & Franceschini test for separation of principal
      components and the hypergeometric probability formula for significance of overlap
      in gene signatures. We perform pathway analysis using LeFEminer and Backward
      Chaining Rule Induction to identify a signaling network that differentiates the
      subset. We identify a larger cohort of samples in the public domain, and use Gene
      Shaving and Robust Bayesian Network Analysis to detect pathways that interact
      with the defining signal. RESULTS: We demonstrate that the two separately
      introduced ER- breast cancer subsets represent the same tumor type, called
      Molecular Apocrine breast cancer. LeFEminer and Backward Chaining Rule Induction
      support a role for AR signaling as a pathway that differentiates this subset from
      others. Gene Shaving and Robust Bayesian Network Analysis detect interactions
      between the AR pathway, EGFR trafficking signals, and ErbB2. CONCLUSION: We
      propose criteria for meta-analysis that are able to demonstrate statistical
      significance in establishing molecular equivalence of subsets across
      institutions. Data mining strategies used here provide an alternative method to
      comparison with cell lines for discovering seminal pathways and interactions
      between signaling networks. Analysis of Molecular Apocrine breast cancer implies
      that therapies targeting AR might be hampered if interactions with ErbB family
      members are not addressed.

PMID- 19747395
TI  - ICRPfinder: a fast pattern design algorithm for coding sequences and its
      application in finding potential restriction enzyme recognition sites.
AB  - BACKGROUND: Restriction enzymes can produce easily definable segments from DNA
      sequences by using a variety of cut patterns. There are, however, no software
      tools that can aid in gene building -- that is, modifying wild-type DNA sequences
      to express the same wild-type amino acid sequences but with enhanced codons,
      specific cut sites, unique post-translational modifications, and other engineered
      in components for recombinant applications. A fast DNA pattern design algorithm,
      ICRPfinder, is provided in this paper and applied to find or create potential
      recognition sites in target coding sequences. RESULTS: ICRPfinder is applied to
      find or create restriction enzyme recognition sites by introducing silent
      mutations. The algorithm is shown capable of mapping existing cut-sites but
      importantly it also can generate specified new unique cut-sites within a
      specified region that are guaranteed not to be present elsewhere in the DNA
      sequence. CONCLUSION: ICRPfinder is a powerful tool for finding or creating
      specific DNA patterns in a given target coding sequence. ICRPfinder finds or
      creates patterns, which can include restriction enzyme recognition sites, without
      changing the translated protein sequence. ICRPfinder is a browser-based
      JavaScript application and it can run on any platform, in on-line or off-line
      mode.

PMID- 19747396
TI  - Therapeutic implications of osteoprotegerin.
AB  - Osteoprotegerin (OPG), a member of the tumor necrosis factor (TNF) receptor
      superfamily, contributes determinatively to the bone remodeling as well as to the
      pathogenetic mechanism of bone malignancies and disorders of mineral metabolism.
      There is additional evidence that OPG can promote cell survival by inhibiting TNF
      related apoptosis-inducing ligand (TRAIL)-induced apoptosis. A number of recent
      in vitro, in vivo and clinical studies have defined the role of the
      RANK/RANKL/OPG pathway in skeletal and vascular diseases. These works were the
      milestone of the deep understanding of the mechanism of OPG. This review provides
      an overview of the potential innovative therapeutic strategies of OPG in
      metastatic breast and prostate carcinoma, multiple myeloma, postmenopausal
      osteoporosis, glucocorticoid-induced osteoporosis and rheumatoid arthritis.
      Special reference is given to the increasing evidence that RANKL and OPG may link
      the skeletal with the vascular system.

PMID- 19747397
TI  - Personal experience with whole-body, low-dosage, digital X-ray scanning (LODOX
      Statscan) in trauma.
AB  - BACKGROUND: Lodox-Statscan is a whole-body, skeletal and soft-tissue, low-dose X
      ray scanner Anterior-posterior and lateral thoraco-abdominal studies are obtained
      in 3-5 minutes with only about one-third of the radiation required for
      conventional radiography. Since its approval by the Food and Drug Administration
      (FDA) in the USA, several trauma centers have incorporated this technology into
      their Advanced Trauma Life Support protocols. This review provides a brief
      overview of the system, and describes the authors' own experience with the
      system. METHODS: We performed a PubMed search to retrieve all references with
      'Lodox' and 'Stat-scan' used as search terms. We furthermore used the google
      search engine to identify existing alternatives. To the best of our knowledge,
      this is the only FDA-approved device of its kind currently used in trauma.
      RESULTS AND CONCLUSION: The intention of our review has been to sensitize the
      readership that such alternative devices exist. The key message is that low
      dosage full body radiography may be an alternative to conventional resuscitation
      room radiography which is usually a prelude to CT scanning (ATLS algorithm). The
      combination of both is radiation intensive and therefore we consider any
      reduction of radiation a success. 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- 19747398
TI  - Characterization of membranous and cytoplasmic EGFR expression in human normal
      renal cortex and renal cell carcinoma.
AB  - Metastatic renal cell carcinoma (RCC) is highly resistant to conventional
      systemic treatments, including chemotherapy, radiotherapy and hormonal therapies.
      Previous studies have shown over-expression of EGFR is associated with high grade
      tumors and a worse prognosis. Recent studies suggest anticancer therapies
      targeting the EGFR pathway have shown promising results in clinical trials of RCC
      patients. Therefore, characterization of the level and localization of EGFR
      expression in RCC is important for target-dependent therapy. In this study, we
      investigated the clinical significance of cellular localization of EGFR in human
      normal renal cortex and RCC. RCC and adjacent normal kidney tissues of 63
      patients were obtained for characterization of EGFR expression. EGFR protein
      expression was assessed by immunohistochemistry on a scale from 0 to 300
      (percentage of positive cells x staining intensity) and Western blotting. EGFR
      membranous staining was significantly stronger in RCC tumors than in normal
      tissues (P < 0.001). In contrast, EGFR cytoplasmic staining was significantly
      higher in normal than in tumor tissues (P < 0.001). The levels of membranous or
      cytoplasmic EGFR expression in RCC tissues were not correlated with sex, tumor
      grade, TNM stage or overall survival (P > 0.05). These results showed abundant
      expression of membranous EGFR in RCC, and abundant expression of cytoplasmic EGFR
      in normal tissues. EGFR expression in RCC was mostly located in the cell
      membrane, whereas the EGFR expression in normal renal tissues was chiefly seen in
      cytoplasm. Our results suggest different locations of EGFR expression may be
      associated with human renal tumorigenesis.

PMID- 19747399
TI  - Iranian nurses' constraint for research utilization.
AB  - BACKGROUND: This paper identifies the views of Iranian clinical nurses regarding
      the utilization of nursing research in practice. There is a need to understand
      what restricts Iranian clinical nurses to use research findings. The aim of this
      study was to identify practicing nurses' view of aspects which they perceived
      constrain them from research utilization that summarizes and uses research
      findings to address a nursing practice problem. METHODS: Data were collected
      during 6 months by means of face-to face interviews follow by one focus group.
      Analysis was undertaken using a qualitative content analysis. RESULTS: Findings
      disclosed some key themes perceived by nurses to restrict them to use research
      findings: level of support require to be research active, to be research minded,
      the extent of nurses knowledge and skills about research and research
      utilization, level of educational preparation relating to using research,
      administration and executive challenges in clinical setting, and theory-practice
      gap. CONCLUSION: This study identifies constraints that require to be overcome
      for clinical nurses to actively get involved in research utilization. In this
      study nurses were generally interested to use research findings. However they
      felt restricted because of lack of time, lack of peer and manager support and
      limited knowledge and skills of the research process. This study also confirms
      that research utilization and the change to research nursing practice are complex
      issues which require both organizational and educational efforts.

PMID- 19747400
TI  - A comparison of course-related stressors in undergraduate problem-based learning
      (PBL) versus non-PBL medical programmes.
AB  - BACKGROUND: Medical students report high levels of stress related to their
      medical training as well as to other personal and financial factors. The aim of
      this study is to investigate whether there are differences in course-related
      stressors reported by medical students on undergraduate problem-based learning
      (PBL) and non-PBL programmes in the UK. METHOD: A cross-sectional study of second
      year medical students in two UK medical schools (one PBL and one non-PBL
      programme) was conducted. A 16-question self-report questionnaire, derived from
      the Perceived Medical Student Stress Scale and the Higher Education Stress
      Inventory, was used to measure course-related stressors. Following univariate
      analysis of each stressor between groups, multivariate logistic regression was
      used to determine which stressors were the best predictors of each course type,
      while controlling for socio-demographic differences between the groups. RESULTS:
      A total of 280 students responded. Compared to the non-PBL students (N = 197),
      the PBL students (N = 83) were significantly more likely to agree that: they did
      not know what the faculty expected of them (Odds Ratio (OR) = 0.38, p = 0.03);
      there were too many small group sessions facilitated only by students resulting
      in an unclear curriculum (OR = 0.04, p < 0.0001); and that there was a lack of
      opportunity to explore academic subjects of interest (OR = 0.40, p = 0.02). They
      were significantly more likely to disagree that: there was a lack of
      encouragement from teachers (OR = 3.11, p = 0.02); and that the medical course
      fostered a sense of anonymity and feelings of isolation amongst students (OR =
      3.42, p = 0.008). CONCLUSION: There are significant differences in the perceived
      course-related stressors affecting medical students on PBL and non-PBL
      programmes. Course designers and student support services should therefore tailor
      their work to minimise, or help students cope with, the specific stressors on
      each course type to ensure optimum learning and wellbeing among our future
      doctors.

PMID- 19747401
TI  - Outcome of gastroplasty and gastric bypass in a single centre in the UK.
AB  - BACKGROUND: Morbid obesity is defined as BMI>40 kg/m2. It affects 124,000 men and
      412,000 women in England and Wales (NICE, July 2002). According to NICE
      guidelines, Bariatric surgery is indicated if the treatments for obesity such as
      exercise, diet and drugs fail. Procedures include laparoscopic gastric banding
      (LGB), vertical banded gastroplasty (VBG), and Gastric Bypass (GB). AIMS: The aim
      of this audit was to determine if NICE guidelines on the use of Bariatric surgery
      in the Manor Hospital, Walsall was being adhered to. Secondary aims were also to
      establish if Bariatric surgery is achieving its goal in the long-term and if
      weight reduction is being maintained in this group of patients. METHODS: A
      retrospective cohort study was carried out on patients who underwent Bariatric
      surgery between 1990 and 2004. Retrieved records were scrutinised and the
      following parameters were collated: pre-operative morbidities, intra and post
      operative complication rates and weight reduction on follow-up. RESULTS: 129
      patients were operated on in the 14 year period. For VBG, 40 out of 105 patients
      had weight gain by the 5th follow-up visit. This compared with 5 out of 18
      patients after the same timescale for the GB group and 1 out of 6 in the LGB
      group. The most common post-operative complication was stenosis (28% of VBG
      group). CONCLUSION: Bariatric surgery is relatively safe as an intervention for
      morbid obesity. Weight loss however is not maintained in the long term. VBG and
      LGB are short term interventions. Further research is required to look into the
      merits of gastric bypass surgery.

PMID- 19747402
TI  - Cost-effectiveness of active transport for primary school children - Walking
      School Bus program.
AB  - BACKGROUND: To assess from a societal perspective the incremental cost
      effectiveness of the Walking School Bus (WSB) program for Australian primary
      school children as an obesity prevention measure. The intervention was modelled
      as part of the ACE-Obesity study, which evaluated, using consistent methods,
      thirteen interventions targeting unhealthy weight gain in Australian children and
      adolescents. METHODS: A logic pathway was used to model the effects on body mass
      index [BMI] and disability-adjusted life years [DALYs] of the Victorian WSB
      program if applied throughout Australia. Cost offsets and DALY benefits were
      modelled until the eligible cohort reached 100 years of age or death. The
      reference year was 2001. Second stage filter criteria ('equity', 'strength of
      evidence', 'acceptability', feasibility', sustainability' and 'side-effects')
      were assessed to incorporate additional factors that impact on resource
      allocation decisions. RESULTS: The modelled intervention reached 7,840 children
      aged 5 to 7 years and cost $AUD22.8M ($16.6M; $30.9M). This resulted in an
      incremental saving of 30 DALYs (7:104) and a net cost per DALY saved of $AUD0.76M
      ($0.23M; $3.32M). The evidence base was judged as 'weak' as there are no data
      available documenting the increase in the number of children walking due to the
      intervention. The high costs of the current approach may limit sustainability.
      CONCLUSION: Under current modelling assumptions, the WSB program is not an
      effective or cost-effective measure to reduce childhood obesity. The attribution
      of some costs to non-obesity objectives (reduced traffic congestion and air
      pollution etc.) is justified to emphasise the other possible benefits. The
      program's cost-effectiveness would be improved by more comprehensive
      implementation within current infrastructure arrangements. The importance of
      active transport to school suggests that improvements in WSB or its variants need
      to be developed and fully evaluated.

PMID- 19747403
TI  - The role of simple mathematical models in malaria elimination strategy design.
AB  - BACKGROUND: Malaria has recently been identified as a candidate for global
      eradication. This process will take the form of a series of national
      eliminations. Key issues must be considered specifically for elimination strategy
      when compared to the control of disease. Namely the spread of drug resistance,
      data scarcity and the adverse effects of failed elimination attempts.
      Mathematical models of various levels of complexity have been produced to
      consider the control and elimination of malaria infection. If available, detailed
      data on malaria transmission (such as the vector life cycle and behaviour, human
      population behaviour, the acquisition and decay of immunity, heterogeneities in
      transmission intensity, age profiles of clinical and subclinical infection) can
      be used to populate complex transmission models that can then be used to design
      control strategy. However, in many malaria countries reliable data are not
      available and policy must be formed based on information like an estimate of the
      average parasite prevalence. METHODS: A simple deterministic model, that requires
      data in the form of a single estimate of parasite prevalence as an input, is
      developed for the purpose of comparison with other more complex models. The model
      is designed to include key aspects of malaria transmission and integrated
      control. RESULTS: The simple model is shown to have similar short-term dynamic
      behaviour to three complex models. The model is used to demonstrate the potential
      of alternative methods of delivery of controls. The adverse effects on clinical
      infection and spread of resistance are predicted for failed elimination attempts.
      Since elimination strategies present an increased risk of the spread of drug
      resistance, the model is used to demonstrate the population level protective
      effect of multiple controls against this very serious threat. CONCLUSION: A
      simple model structure for the elimination of malaria is suitable for situations
      where data are sparse yet strategy design requirements are urgent with the caveat
      that more complex models, populated with new data, would provide more
      information, especially in the long-term.

PMID- 19747404
TI  - Restless Legs Syndrome in shift workers: A cross sectional study on male assembly
      workers.
AB  - BACKGROUND: Restless Legs Syndrome (RLS) is a common neurological movement
      disorder characterized by symptoms that follow a circadian pattern. Night and
      rotating shift work schedules exert adverse effects on functions of the human
      body by disturbing circadian rhythms, and they are known to cause sleep
      disturbances and insomnia. In this paper, we investigate the possible association
      between shift work and RLS. METHODS: This cross sectional study was conducted in
      an automobile manufacturing factory in Tehran, Iran. A total of 780 male assembly
      workers were recruited in three groups, each with 260 workers: workers on a
      permanent morning shift (A) and two different rotating shift schedules (B and C)
      with morning, afternoon and night shifts. We used the international RLS study
      group criteria for diagnosis of RLS, and the severity scale for severity
      assessment in subjects with RLS. Self administered questionnaires were used to
      gather information on age, smoking, work history, medical condition, and
      existence and severity of RLS symptoms. RESULTS: The prevalence of RLS was
      significantly higher in rotational shift workers (15%) than workers with
      permanent morning work schedule (8.5%). In workers suffering from RLS, we found
      greater mean values of age and work experience, higher percentages of drug
      consumption, smoking, and co-morbid illnesses compared with subjects who did not
      have RLS, although these differences were statistically significant only for age,
      work experience and drug consumption. CONCLUSION: Rotational shift work acts as a
      risk or exacerbating factor for Restless Legs Syndrome.

PMID- 19747405
TI  - Laser capture microdissection of gonads from juvenile zebrafish.
AB  - BACKGROUND: Investigating gonadal gene expression is important in attempting to
      elucidate the molecular mechanism of sex determination and differentiation in the
      model species zebrafish. However, the small size of juvenile zebrafish and
      correspondingly their gonads complicates this type of investigation. Furthermore,
      the lack of a genetic sex marker in juvenile zebrafish prevents pooling gonads
      from several individuals. The aim of this study was to establish a method to
      isolate the gonads from individual juvenile zebrafish allowing future
      investigations of gonadal gene expression during sex determination and
      differentiation. METHODS: The laser capture microdissection technique enables
      isolation of specific cells and tissues and thereby removes the noise of gene
      expression from other cells or tissues in the gene expression profile. A protocol
      developed for laser microdissection of human gonocytes was adjusted and optimised
      to isolate juvenile zebrafish gonads. RESULTS: The juvenile zebrafish gonad is
      not morphologically distinguishable when using dehydrated cryosections on
      membrane slides and a specific staining method is necessary to identify the
      gonads. The protocol setup in this study allows staining, identification,
      isolation and subsequent RNA purification and amplification of gonads from
      individual juvenile zebrafish thereby enabling gonadal gene expression profiling.
      CONCLUSION: The study presents a protocol for isolation of individual juvenile
      zebrafish gonads, which will enable future investigations of gonadal gene
      expression during the critical period of sex differentiation. Furthermore, the
      presented staining method is applicable to other species as it is directed
      towards alkaline phosphatase that is expressed in gonocytes and embryonic stem
      cells, which is conserved among vertebrate species.

PMID- 19747406
TI  - Perioperative indocyanine green clearance is predictive for prolonged intensive
      care unit stay after coronary artery bypass grafting--an observational study.
AB  - INTRODUCTION: During cardiac surgery with cardiopulmonary bypass (CPB)
      haemodilution occurs. Hepatic dysfunction after CPB is a rare, but serious,
      complication. Clinical data have validated the plasma-disappearance rate of
      indocyanine green (PDR ICG) as a marker of hepatic function and perfusion.
      Primary objective of this analysis was to investigate the impact of
      haemodilutional anaemia on hepatic function and perfusion by the time course of
      PDR ICG and liver enzymes in elective CABG surgery. Secondary objective was to
      define predictors of prolonged ICU treatment like decreased PDR ICG after
      surgery. METHODS: 60 Patients were subjected to normothermic CPB with predefined
      levels of haemodilution anaemia (haemotacrit (Hct) of 25% versus 20% during CPB).
      Hepatic function and perfusion was assessed by PDR ICG, plasma levels of
      aspartate aminotransferase (ASAT) and alpha-GST. Prolonged ICU treatment was
      defined as treatment >or= 48 hours. RESULTS: Logistic regression analysis showed
      that all postoperative measurements of PDR ICG (P < 0.01), and the late
      postoperative ASAT (P < 0.01) measurement were independent risk factors for
      prolonged ICU treatment. The predictive capacity for prolonged ICU treatment was
      best of the PDR ICG one hour after admission to the ICU. Furthermore, the time
      course of PDR ICG as well as ASAT and alpha-GST did not differ between groups of
      haemodilutional anaemia. CONCLUSIONS: Our study provides evidence that impaired
      PDR ICG as a marker of hepatic dysfunction and hypoperfusion may be a valid
      marker of prolonged ICU treatment. Additionally this study provides evidence that
      haemodilutional anaemia to a Hct of 20% does not impair hepatic function and
      perfusion. TRIAL REGISTRATION: [ISRCTN35655335].

PMID- 19747407
TI  - Update on comparative genome mapping between Malus and Pyrus.
AB  - BACKGROUND: Comparative genome mapping determines the linkage between homologous
      genes of related taxa. It has already been used in plants to characterize
      agronomically important genes in lesser studied species, using information from
      better studied species. In the Maloideae sub-family, which includes fruit species
      such as apple, pear, loquat and quince, genome co-linearity has been suggested
      between the genera Malus and Pyrus; however map comparisons are incomplete to
      date. FINDINGS: Genetic maps for the apple rootstocks 'Malling 9' ('M.9') (Malus
      x domestica) and 'Robusta 5' ('R5') (Malus x robusta), and pear cultivars
      'Bartlett' and 'La France' (Pyrus communis) were constructed using Simple
      Sequence Repeat (SSR) markers developed from both species, including a new set of
      73 pear Expressed Sequence Tag (EST) SSR markers. Integrated genetic maps for
      apple and pear were then constructed using 87 and 131 SSR markers in common,
      respectively.The genetic maps were aligned using 102 markers in common, including
      64 pear SSR markers and 38 apple SSR markers. Of these 102 markers, 90 anchor
      markers showed complete co-linearity between the two genomes. CONCLUSION: Our
      alignment of the genetic maps of two Malus cultivars of differing species origin
      with two Pyrus communis cultivars confirms the ready transferability of SSR
      markers from one genus to the other and supports a high level of co-linearity
      within the sub-family Maloideae between the genomes of Malus and Pyrus.

PMID- 19747408
TI  - Function of caspase-14 in trophoblast differentiation.
AB  - BACKGROUND: Within the human placenta, the cytotrophoblast consists of a
      proliferative pool of progenitor cells which differentiate to replenish the
      overlying continuous, multi-nucleated syncytiotrophoblast, which forms the
      barrier between the maternal and fetal tissues. Disruption to trophoblast
      differentiation and function may result in impaired fetal development and
      preeclampsia. Caspase-14 expression is limited to barrier forming tissues. It
      promotes keratinocyte differentiation by cleaving profilaggrin to stabilise
      keratin intermediate filaments, and indirectly providing hydration and UV
      protection. However its role in the trophoblast remains unexplored. METHODS:
      Using RNA Interference the reaction of control and differentiating trophoblastic
      BeWo cells to suppressed caspase-14 was examined for genes pertaining to
      hormonal, cell cycle and cytoskeletal pathways. RESULTS: Transcription of hCG,
      KLF4 and cytokeratin-18 were increased following caspase-14 suppression
      suggesting a role for caspase-14 in inhibiting their pathways. Furthermore, hCG,
      KLF4 and cytokeratin-18 protein levels were disrupted. CONCLUSION: Since
      expression of these molecules is normally increased with trophoblast
      differentiation, our results imply that caspase-14 inhibits trophoblast
      differentiation. This is the first functional study of this unusual member of the
      caspase family in the trophoblast, where it has a different function than in the
      epidermis. This knowledge of the molecular underpinnings of trophoblast
      differentiation may instruct future therapies of trophoblast disease.

PMID- 19747409
TI  - Asian Indian adolescents from Guadeloupe are fatter than their island
      counterparts.
AB  - The present study aimed at comparing the anthropometric profile of Asian Indian
      adolescents from Guadeloupe with that of their island counterparts. A total of
      720 voluntary 11- to 17-year-old students participated: 180 Asian Indians and 540
      age- and sex-matched students of other origin. Weight and height were measured to
      calculate the BMI. Waist and hip circumferences and bicipital, tricipital,
      subscapular and supra-iliac skinfold thicknesses were assessed. The percentage of
      body fat was estimated by bioelectrical impedance analysis. Obesity was defined
      from BMI according to the International Obesity Task Force recommendations. Asian
      Indians were smaller and lighter than their counterparts. They had a higher body
      fat percentage even after adjustment on BMI but the prevalence of obesity did not
      differ, with an overall prevalence of 5.69 (95 % CI 5.67, 5.71) %. No principal
      effects of ethnicity on waist and hip circumferences or the waist:hip ratio were
      evidenced. The sum of the four skinfold thicknesses was the strongest predictor
      of body fat percentage, and the adjustment of overall body fat on subcutaneous
      fat cancelled the effect of ethnicity on this dependent variable. The present
      study found that Asian Indian adolescents from Guadeloupe had the same tendency
      toward higher body fat and body fat-for-BMI as previously documented in Asian
      Indian adults. It raises the hypothesis of a higher cardiovascular risk in this
      ethnic group from adolescence and questions the validity of using common BMI
      references for screening obesity in multiethnic communities.

PMID- 19747410
TI  - Consumption of a fermented dairy product containing the probiotic Lactobacillus
      casei DN-114001 reduces the duration of respiratory infections in the elderly in
      a randomised controlled trial.
AB  - Common infectious diseases (CID) of the airways and the gastrointestinal tract
      are still a considerable cause of morbidity and mortality in elderly. The present
      study examined the beneficial effect of a dairy product containing the probiotic
      strain Lactobacillus casei DN-114 001 (fermented product) on the resistance of
      free-living elderly to CID. The study was multicentric, double blind and
      controlled, involving 1072 volunteers (median age = 76.0 years) randomised for
      consumption of either 200 g/d of fermented (n 537) or control (non-fermented)
      dairy product (n 535) for 3 months, followed by an additional 1 month's follow
      up. The results showed that, when considering all CID, the fermented product
      significantly reduced the average duration per episode of CID (6.5 v. 8 d in
      control group; P = 0.008) and the cumulative duration of CID (7 v. 8 d in control
      group; P = 0.009). Reduction in both episode and cumulative durations was also
      significant for all upper respiratory tract infections (URTI; P < 0.001) and for
      rhinopharyngitis (P < 0.001). This was accompanied with an increase of L. casei
      species in stools throughout the fermented product consumption (2-3.8 x 107
      equivalents of colony-forming unit/g of stools, P < 0.001). The cumulative number
      of CID (primary outcome) was not different between groups nor was the CID
      severity, fever, pathogens' occurrence, medication, immune blood parameters and
      quality of life. The fermented product was safe and well tolerated. In
      conclusion, consumption of a fermented dairy product containing the probiotic
      strain L. casei DN-114 001 in elderly was associated with a decreased duration of
      CID in comparison with the control group, especially for URTI such as
      rhinopharyngitis.

PMID- 19747411
TI  - Fish oil diets do not improve insulin sensitivity and secretion in healthy adult
      male pigs.
AB  - The effects of long-term dietary supplementation of fish oil (n-3 PUFA-rich) in
      adult male pigs on body condition as well as insulin sensitivity and secretion
      were examined. Fifteen Duroc boars aged 204.5 (sd 9.4) d (body weight 145.8 (sd
      16.8) kg) received daily 2.5 kg basal diet with a supplement of: (1) 62 g
      hydrogenated animal fat (n 5); (2) 60 g menhaden oil containing 10.8 g DHA and
      9.0 g EPA (n 6); (3) 60 g tuna oil containing 19.8 g DHA and 3.9 g EPA (n 4).
      Rations were balanced to be isoenergetic. After 7 months of treatments, oral
      glucose and meal tolerance tests were conducted after insertion of a catheter
      into the jugular vein. Dietary supplementation with n-3 PUFA altered the blood
      plasma profile: DHA and EPA increased whereas arachidonic acid decreased (P <
      0.01). Plasma glucose, insulin and C-peptide responses to oral glucose and the
      test meal were not affected by treatments (P>0.34). For all animals, total body
      fat estimated from body weight and back fat thickness was correlated with both
      beta-cell function (by homeostasis model assessment (HOMA); r+0.63) and insulin
      sensitivity (index of whole-body insulin sensitivity and by HOMA; r - 0.63 and
      r+0.66, respectively). In conclusion, long-term supplementation with dietary n-3
      PUFA did not affect insulin metabolism in healthy adult male pigs. The
      relationship between body fat and insulin sensitivity, well documented in human
      subjects, suggests that the adult male pig could be a promising animal model for
      studies on insulin metabolism.

PMID- 19747412
TI  - The longitudinal change in anthropometric measurements and the association with
      physical function decline in Japanese community-dwelling frail elderly.
AB  - Although anthropometric parameters have been extensively studied regarding their
      relationship to physical function status, the association between these
      parameters and the activity of daily living (ADL) function remains controversial.
      We investigated whether BMI or mid-upper arm circumference (AC) is an indication
      of variation in the physical functioning of the frail elderly. The present study
      was a prospective cohort analysis of 543 community-dwelling frail elderly. Data
      included the participants' demographic characteristics, basic ADL, comorbidity
      and anthropometric measurements at baseline and at 2-year follow-up. Logistic
      regression models were used to investigate the association between ADL status and
      anthropometric measurements during the study period. Among the 543 participants,
      418 maintained or improved their ADL status, while 125 showed an ADL decline
      during the study period. Multivariate logistic regression analysis showed that
      BMI and AC levels or ADL status at baseline were not independent predictors of
      the loss of ADL function or the decline in these anthropometric measurements
      during the study period, respectively. However, the decline in BMI and AC levels
      and the loss of ADL function were associated with each other during the study
      period. There is an association between the negative changes in anthropometric
      measurements during the follow-up period and the decline in ADL function during a
      2-year follow-up in community-dwelling frail elderly.

PMID- 19747413
TI  - Zinc and DHA have opposing effects on the expression levels of histones H3 and H4
      in human neuronal cells.
AB  - Zn and DHA have putative neuroprotective effects and these two essential
      nutrients are known to interact biochemically. We aimed to identify novel protein
      candidates that are differentially expressed in human neuronal cell line M17 in
      response to Zn and DHA that would explain the molecular basis of this
      interaction. Two-dimensional gel electrophoresis and MS were applied to identify
      major protein expression changes in the protein lysates of human Ml7 neuronal
      cells that had been grown in the presence and absence of Zn and DHA. Proteomic
      findings were further investigated using Western immunoblot and real-time PCR
      analyses. Four protein spots, which had significant differential expression, were
      identified and selected for in-gel trypsin digestion followed by matrix-assisted
      laser desorption ionisation MS analysis. The resultant peptide mass fingerprint
      for each spot allowed their respective identities to be deduced. Two human
      histone variants H3 and H4 were identified. Both H3 and H4 were downregulated by
      Zn in the absence of DHA (Zn effect) and upregulated by DHA (DHA effect) in the
      presence of Zn (physiological condition). These proteomic findings were further
      supported by Western immunoblot and real-time PCR analyses using H3- and H4
      specific monoclonal antibodies and oligonucleotide primers, respectively. We
      propose that dietary Zn and DHA cause a global effect on gene expression, which
      is mediated by histones. Such novel information provides possible clues to the
      molecular basis of neuroprotection by Zn and DHA that may contribute to the
      future treatment, prevention and management of neurodegenerative diseases such as
      Alzheimer's disease.

PMID- 19747414
TI  - Genotype x nutrient association of common polymorphisms in obesity-related genes
      with food preferences and time structure of energy intake.
AB  - Personal food preferences can either enhance or suppress the development of
      obesity and the selection and proportion of macronutrients in the diet seem to
      have a heritable component. In the present study, we therefore focused on dietary
      composition as a specific trait related to obesity and we determined whether
      genetic variations in leptin (LEP), LEP receptor (LEPR), adiponectin (ADIPOQ), IL
      6 and pro-opiomelanocortin (POMC) underlie specific native food preferences and
      obesity-related anthropometric parameters. The total of 409 individuals of Czech
      Caucasian origin were enrolled into the present study and 7 d food records were
      obtained from the study subjects along with selected anthropometric measurements.
      In a subset of study subjects, plasma levels of ADIPOQ, LEP and soluble LEPR were
      measured. Independently of the BMI of the individuals, common variations in LEP
      and LEPR genes were associated with specific eating patterns, mainly with respect
      to timing of eating. The LEP + 19A/G polymorphism served as an independent
      predictor for BMI, percentage of body fat and skinfold thickness and
      significantly affected the time structure of the daily energy intake. The POMC
      RsaI polymorphism was associated with percentage of body fat. The ADIPOQ 45 T/G
      polymorphism was associated with the thickness of the subscapular skinfold. The
      LEPR Gln223Arg polymorphism was associated with multiple parameters, including
      diastolic blood pressure, meal sizes during the day and plasma ADIPOQ levels. In
      a separate analysis, soluble leptin receptor (sObR) plasma levels and LEP:sObR
      ratio were significantly correlated with systolic blood pressure (beta = - 0.66,
      P = 0.002; beta = - 1.23, P = 0.02) and sObR plasma levels also served as an
      independent predictor for diastolic blood pressure (beta = - 0.50; P = 0.04). To
      conclude, we report common allelic variants associated with specific feeding
      behaviour and obesity-related anthropometric traits. Moreover, we identified
      allelic variants that significantly influence the time structure of food intake
      during the day.

PMID- 19747415
TI  - Protective effect of serotonin derivatives on glucose-induced damage in PC12 rat
      pheochromocytoma cells.
AB  - Oxidative damage is believed to be associated with ageing, cancer and several
      degenerative diseases. Previous reports have shown that safflower-seed extract
      and its major antioxidant constituents, serotonin hydroxycinnamic amides, possess
      a powerful free radical-scavenging and antioxidative activity, paying particular
      attention to atherosclerotic reactive oxygen species (ROS)-related dysfunctions.
      In the present report, we examined a still unknown cell-based mechanism of
      serotonin derivatives against ROS-related neuronal damage, phenomena that
      represent a crucial event in neurodegenerative diseases. Serotonin derivatives N
      (p-coumaroyl)serotonin and N-feruloylserotonin exerted a protective effect on
      high glucose-induced cell death, inhibited the activation of caspase-3 which
      represents the last and crucial step within the cascade of events leading to
      apoptosis, and inhibited the overproduction of the mitochondrial superoxide,
      which represents the most dangerous radical produced by hyperglycaemia, by acting
      as scavengers of the superoxide radical. In addition, serotonin derivative
      concentration inside the cells and inside the mitochondria was increased in a
      time-dependent manner. Since recent studies support the assertion that
      mitochondrial dysfunctions related to oxidative damage are the major contributors
      to neurodegenerative diseases, these preliminary cell-based results identify a
      mitochondria-targeted antioxidant property of serotonin derivatives that could
      represent a novel therapeutic approach against the neuronal disorders and
      complications related to ROS.

PMID- 19747416
TI  - Intake and home use of olive oil or mixed oils in relation to healthy lifestyles
      in a Mediterranean population. Findings from the prospective Pizarra study.
AB  - Discordances exist in epidemiological studies regarding the association between
      the intake of nutrients and death and disease. We evaluated the social and health
      profile of persons who consumed olive oil in a prospective population cohort
      investigation (Pizarra study) with a 6-year follow-up. A food frequency
      questionnaire and a 7 d quantitative questionnaire were administered to 538
      persons. The type of oil used in food preparation was determined by direct
      measurement of the fatty acids in samples obtained from the kitchens of the
      participants at baseline and after follow-up for 6 years. The fatty acid
      composition of the serum phospholipids was used as an endogenous marker of the
      type of oil consumed. Total fat intake accounted for a mean 40 % of the energy
      (at baseline and after follow-up). The concordance in intake of MUFA over the
      study period was high. The fatty acid composition of the serum phospholipids was
      significantly associated with the type of oil consumed and with fish intake. The
      concentration of polar compounds and polymers, indicative of degradation, was
      greater in oils from the kitchens where sunflower oil or refined olive oil was
      used, in oils used for deep frying and in oils that had been reused for frying
      five times or more. Consumption of olive oil was directly associated with
      educational level. Part of the discordance found in epidemiological studies
      between diet and health may be due to the handling of oils during food
      preparation. The intake of olive oil is associated with other healthy habits.

PMID- 19747417
TI  - Genistein inhibits glucose and sulphate transport in isolated rat liver
      lysosomes.
AB  - Genistein and daidzein are known to have both beneficial and adverse effects on
      human health due to their many biological actions at the cellular level. Both
      isoflavones have been shown to inhibit GLUT-mediated glucose transport across the
      plasma membrane of mammalian cells. Since lysosomal membrane transport is
      essential for maintaining cellular homeostasis, the present study examined the
      effects of genistein and daidzein on glucose and sulphate transport in isolated
      rat liver lysosomes. Both genistein and daidzein significantly inhibited
      lysosomal glucose uptake. Genistein was a more potent glucose transport inhibitor
      than daidzein, with a half-maximum inhibitory concentration (IC(50)) of 45
      micromol/l compared with 71 micromol/l for daidzein. Uptake kinetics of d-glucose
      showed a significant decrease in Vmax (control:genistein treat = 1489 (sem
      91):507 (sem 76) pmol/unit of beta-hexosaminidase per 15 s) without a change in
      K(m). The presence of 50 microm-genistein in the medium also reduced glucose
      efflux from lysosomes preloaded with 100 mm-d-glucose. Genistein also inhibited
      lysosomal sulphate transport. Similar to its effects on glucose uptake kinetics,
      genistein treatment caused a significant decrease in sulphate uptake V(max)
      (control:genistein treat = 87 (sem 4):59 (sem 5) pmol/unit of beta-hexosaminidase
      per 30 s), while the K(m) was not affected. The evidence provided by the present
      study suggests that the most likely mechanism of lysosomal glucose transport
      inhibition by genistein is via direct interaction between genistein and the
      transporter, rather than mediation by tyrosine kinase inactivation. Genistein
      likely has a similar mechanism of directly inhibiting sulphate transporter.

PMID- 19747418
TI  - The relationship between fasting plasma concentrations of selected flavonoids and
      their ordinary dietary intake.
AB  - Epidemiological studies suggest that a diet high in flavonoids protects against
      chronic diseases such as CVD and cancer. The objective of the present study was
      to evaluate the relationship between the intake of quercetin, kaempferol,
      isorhamnetin, apigenin and luteolin and their corresponding plasma
      concentrations, and further to explore whether these flavonoids can serve as
      biomarkers of their intake. Flavonoid intake and their plasma concentrations were
      analysed in ninety-two subjects consuming their habitual diet. Flavonoid intake
      was estimated with 7-d dietary records using available data on the flavonoid
      content of food. Plasma flavonoid concentrations were quantified by HPLC. In
      addition, we undertook a dietary intervention study to investigate plasma
      apigenin concentration after the consumption of celery leaf. The mean intake
      estimates of quercetin, kaempferol, isorhamnetin, apigenin and luteolin amounted
      to 13.58, 14.97, 12.31, 4.23 and 8.08 mg/d, respectively. The corresponding mean
      plasma concentrations were 80.23, 57.86, 39.94, 10.62 and 99.90 nmol/l. The mean
      7 d intake of five flavonoids was positively correlated to their corresponding
      plasma concentrations, with correlation coefficients ranging from 0.33 to 0.51 (P
      < 0.05). In the dietary intervention study, the plasma apigenin concentration
      rose after celery leaf ingestion, and fell within 28 h to below the limit of
      detection (2.32 nmol/l). The present results suggest that quercetin, kaempferol,
      isorhamnetin, apigenin and luteolin are bioavailable from the diet. The levels of
      fasting plasma flavonoids seem to be suitable biomarkers of short-term intake.
      The combination of plasma flavonoids with their intake may prove useful when the
      possible health-protective effects of flavonoids are studied.

PMID- 19747419
TI  - Classification of individuals with dyslipidaemia controlled by statins according
      to plasma biomarkers of oxidative stress using cluster analysis.
AB  - Oxidative stress is a physiological condition that is associated with
      atherosclerosis, and it can be influenced by diet. Our objective was to group
      fifty-seven individuals with dyslipidaemia controlled by statins according to
      four oxidative biomarkers, and to evaluate the diet pattern and blood
      biochemistry differences between these groups. Blood samples were collected and
      the following parameters were evaluated: diet intake; plasma fatty acids;
      lipoprotein concentration; glucose; oxidised LDL (oxLDL); malondialdehyde (MDA);
      total antioxidant activity by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric
      reducing ability power assays. Individuals were separated into five groups by
      cluster analysis. All groups showed a difference with respect to at least one of
      the four oxidative stress biomarkers. The separation of individuals in the first
      axis was based upon their total antioxidant activity. Clusters located on the
      right side showed higher total antioxidant activity, higher myristic fatty acid
      and lower arachidonic fatty acid proportions than clusters located on the left
      side. A negative correlation was observed between DPPH and the peroxidability
      index. The second axis showed differences in oxidation status as measured by MDA
      and oxLDL concentrations. Clusters located on the upper side showed higher
      oxidative status and lower HDL cholesterol concentration than clusters located on
      the lower side. There were no differences in diet among the five clusters.
      Therefore, fatty acid synthesis and HDL cholesterol concentration seem to exert a
      more significant effect on the oxidative conditions of the individuals with
      dyslipidaemia controlled by statins than does their food intake.

PMID- 19747420
TI  - The effect of the protein level in a pre-starter diet on the post-hatch
      performance and activation of ribosomal protein S6 kinase in muscle of neonatal
      broilers.
AB  - The cytoplasmic serine/threonine ribosomal protein S6 kinase (S6K1) plays a
      critical role in controlling protein translation. There is evidence that amino
      acids regulate S6K1 and protein synthesis in avian species, but the effect of
      dietary protein level on the activation of S6K1 in neonatal chicks is unknown.
      Therefore, the aim of the present experiment was to investigate the effect of
      different protein levels, supplied during the first 5 d post-hatch, on body
      growth, breast muscle development and on the activation of S6K1 and its
      downstream target, the S6, in neonatal chicks. Chicks were fed a pre-starter diet
      during the first 5 d post-hatch containing low (19.6 % crude protein (CP); LP),
      medium (23.1 % CP; MP) or high (26.7 % CP) levels (HP) of protein. Weight gain of
      chicks fed the HP diet was higher (P < 0.05) compared with those fed the LP diet
      during day (d)3-d5 and the numerical advantage of this group was maintained from
      d2 to d7. On d2 and d3, greater levels of S6K1 and S6 phosphorylation and/or
      activity were observed in chicks receiving the HP diet compared with LP and MP
      diets, without differences between results of the latter two dietary treatments.
      In conclusion, the present results suggest that early protein nutrition impacts
      the development of broiler chicks.

PMID- 19747421
TI  - Prevalence and correlates of clinically significant depressive symptoms among
      elderly people in Sri Lanka: findings from a national survey.
AB  - BACKGROUND: Elderly Sri Lankans (11.2% of the nation's population) have witnessed
      many years of ethnic conflict, a destructive tsunami and increasing emigration of
      young adults. However, very little is known about the prevalence and correlates
      of depression among them. The present study utilizes data from a national aging
      survey to document the prevalence and correlates of clinically significant
      depressive symptoms among community-dwelling elderly Sri Lankans (aged > or =60
      years). METHODS: The 15-item Geriatric Depression Scale (GDS-15) was administered
      to 1181 elderly Sri Lankans; the presence of clinically significant depressive
      symptoms was defined as a GDS-15 score of > or =6. Sociodemographic and health
      correlates of depressive symptoms were assessed using logistic regression
      analysis. Interactions between gender and other correlates were also assessed.
      RESULTS: The prevalence of depressive symptoms was observed to be 27.8% overall:
      24.0% for men, and 30.8% for women. Certain subgroups of the elderly, i.e. those
      with disabilities, functional limitations, perceived income inadequacy,
      minorities, and elderly living alone, were significantly more likely to report
      depressive symptoms. There was a significant interaction between gender and
      ethnicity. CONCLUSION: The prevalence of depressive symptoms among Sri Lankan
      elderly people is higher than that reported for most Asian countries. Clinicians
      and caregivers need to be aware of the potential presence of depressive symptoms
      among the elderly, especially among those with lower educational levels,
      functional limitations, hearing difficulty, physical disability, perceived income
      inadequacy, and among those who live alone, and ethnic minority males.

PMID- 19747422
TI  - Top cited papers in International Psychogeriatrics: 6c. Tracking cognitive
      decline in Alzheimer's disease using the Mini-mental State Examination: a meta
      analysis ("mini" is not necessarily trivial!).

PMID- 19747423
TI  - Why suicide? Elderly people who committed suicide and their experience of life in
      the period before their death.
AB  - BACKGROUND: The objective of this study is to acquire an understanding of the
      suicides among a group of elderly people by studying how they experienced their
      existence towards the end of life. METHODS: This is a psychological autopsy study
      based on qualitative interviews with 63 informants in relation to 23 suicides
      committed by persons aged over 65 in Norway. Informants who knew the deceased
      persons well describe what the elderly person communicated to them about their
      experience of life in the period before the suicide and how they as informants
      saw and understood this. The informants comprise relatives, family doctors and
      home-based care nurses. The analysis of the interviews follows the systematic
      text condensation method. RESULTS: The descriptions are divided into three main
      elements: the elderly persons' experiences of life, their perception of
      themselves, and their conceptions of death. "Experience of life" has two sub
      topics: this life has been lived and life as a burden. Everything that had given
      value to their life had been lost and life was increasingly experienced as a
      burden. Their "perception of themselves" concerned losing oneself. Functional
      decline meant that they no longer had freedom of action and self-determination.
      "Conceptions of death" involve the following sub-topics:
      acknowledgement/acceptance and death is better than life. Life had entered into
      its final phase, and they seemed to accept death. For some time, many of them had
      expressed the wish to die. CONCLUSIONS: The results lead us to argue that their
      suicides should be considered as existential choices. The sum total of the
      different forms of strain had made life a burden they could no longer bear. Age
      meant that they were in a phase of life that entailed closeness to death, which
      they could also see as a relief.

PMID- 19747424
TI  - The emergence of the novel H1N1 virus: implications for global mental health.

PMID- 19747425
TI  - Screening properties of the German IQCODE with a two-year time frame in MCI and
      early Alzheimer's disease.
AB  - BACKGROUND: The Informant Questionnaire on Cognitive Decline in the Elderly
      (IQCODE) is a widely used screening tool for dementia. We aimed to determine the
      ability of the German version of the 16-item IQCODE with a two-year time frame to
      discriminate healthy mature control participants (NC) from mild cognitive
      impairment (MCI) and probable early Alzheimer's disease (AD) patients (all with
      Mini-mental State Examination (MMSE) scores >or= 24/30) and to optimize
      diagnostic discriminability by shortening the IQCODE. METHODS: 453 NC (49.7%
      women, age = 69.5 years +/- 8.2, education = 12.2 +/- 2.9), 172 MCI patients
      (41.9% women, age = 71.5 years +/- 8.8, education = 12.3 +/- 3.1) and 208 AD
      patients (59.1% women, age = 76.0 years +/- 6.4, education = 11.4 +/- 2.9)
      participated. Stepwise binary logistic regression analyses (LR) were used to
      shorten the test. Receiver operating characteristic curves (ROC) determined
      sensitivities, specificities, and correct classification rates (CCRs) for (a) NC
      vs. all patients; (b) NC vs. MCI; and (c) NC vs. AD patients. RESULTS: The mean
      IQCODE was 3.00 for NC, 3.35 for MCI, and 3.73 for AD. CCRs were 85.5% (NC
      patient group), 79.9% (NC-MCI), and 90.7% (NC-AD), respectively. The diagnostic
      discriminability of the shortened 7-item IQCODE (i.e. items 1, 2, 3, 5, 7, 10,
      14) was comparable with the longer version (i.e. 7-item CCRs: NC-patient group:
      85.3%; NC-MCI: 80.1%, NC-AD: 90.5%). CONCLUSIONS: The German 16-item IQCODE with
      two-year time frame showed excellent screening properties for MCI and early AD
      patients. An abbreviated 7-item version demonstrated equally high diagnostic
      discriminability, thus allowing for more economical screening.

PMID- 19747426
TI  - alpha-Synuclein antibodies recognize a protein present at lower levels in the CSF
      of patients with dementia with Lewy bodies.
AB  - BACKGROUND: Dementia with Lewy bodies (DLB) accounts for 15-20% of the millions
      of people worldwide with dementia. Accurate diagnosis is essential to avoid harm
      and optimize clinical management. There is therefore an urgent need to identify
      reliable biomarkers. METHODS: Mass spectrometry was used to determine the
      specificity of antibody alpha-synuclein (211) for alpha-synuclein. Using gel
      electrophoresis we measured protein levels detected by alpha-synuclein specific
      antibodies in the cerebrospinal fluid (CSF) of DLB patients and compared them to
      age matched controls. RESULTS: A 24 kDa band was detected using alpha-synuclein
      specific antibodies which was significantly reduced in the CSF of DLB patients
      compared to age matched controls (p < 0.05). Further analysis confirmed that even
      DLB patients with mild dementia showed significant reductions in this protein in
      comparison to controls. CONCLUSIONS: The current study emphasizes the necessity
      for further studies of CSF alpha-synuclein as a biomarker of DLB and extends our
      previous knowledge by establishing a potential relationship between alpha
      synuclein and the severity of cognitive impairment. The identification of this 24
      kDa protein is the next important step in these studies.

PMID- 19747427
TI  - Vitamin A status is associated with T-cell responses in Bangladeshi men.
AB  - Recommendations for vitamin A intake are based on maintaining liver stores of >
      or = 0.070 micromol/g, which is sufficient to maintain normal vision. We propose
      that higher levels may be required to maintain normal immune function. To test
      this hypothesis, we conducted an 8-week residential study among thirty-six
      healthy Bangladeshi men with low vitamin A stores. Subjects were randomised to
      receive vitamin A (240 mg in four doses) or placebo during study weeks 2 and 3.
      Vitamin A stores were estimated by isotopic dilution at week 8. Total T-cells,
      the naive T-cells:memory T-cells ratio and mitogen-induced lymphocyte
      proliferation were positively and significantly correlated with vitamin A stores
      (P < 0.05). Mitogen-stimulated IL-2, IL-4 and TNFalpha increased significantly (P
      < 0.05) in the vitamin A but not placebo group after supplementation, while IL-10
      production was significantly and negatively correlated with vitamin A stores (P <
      0.05). Segmented linear regression analysis revealed that naive T-cell counts and
      T-cell blastogenesis were positively associated with vitamin A stores above but
      not below 0.070 mumol/g liver. These data show that increasing vitamin A stores
      above the level that maintains normal vision enhances some measures of T-cell
      mediated immunity, suggesting a difference in requirements for maintaining vision
      and immune function.

PMID- 19747428
TI  - Maternal alcohol consumption may influence cord blood ascorbic acid
      concentration: findings from a study of Brazilian mothers and their newborns.
AB  - Studies that have investigated ascorbic acid (AA) concentrations in cord blood
      have pointed to significant associations with maternal blood AA concentrations,
      smoking, age, diet, type of delivery, duration of gestation, fetal distress and
      birth weight. The aim of the present study was to determine the relationship
      between cord blood AA concentrations in newborns and maternal characteristics. A
      total of 117 Brazilian healthy parturients were included in this cross-sectional
      study. The concentrations of AA in blood were determined by the HPLC method. Data
      concerning socio-economic, demographic, obstetric, nutritional and health
      characteristics of the parturients, including alcohol consumption and smoking
      habit, were assessed by a standardised questionnaire. A FFQ was used to
      investigate the intake of foods rich in vitamin C. Cord blood AA concentration
      was significantly correlated with per capita income (r 0.26; P = 0.005), maternal
      blood AA concentration (r 0.48; P < 0.001) and maternal vitamin C-rich food
      intake score (r 0.36; P < 0.001). The linear regression model including maternal
      AA concentration, alcohol consumption, smoking, parity, vitamin C-rich food
      intake score and per capita income explained 31.13 % of the variation in cord
      blood AA concentrations in newborns. We recommend further experimental studies to
      assess the effects of ethanol on placental AA uptake, and epidemiological cohort
      studies to evaluate in detail the influence of maternal alcohol consumption on
      cord blood AA concentrations.

PMID- 19747429
TI  - Efficacy and safety of azelastine 0.15% nasal spray administered once daily in
      subjects with seasonal allergic rhinitis.
AB  - Azelastine nasal spray is commercially available as a 0.1% w/v solution and is
      recommended for twice-daily dosing. Increasing the azelastine concentration to
      0.15% may be effective with once-daily dosing without increasing the incidence of
      adverse events. This study evaluated the efficacy and safety of azelastine 0.15%
      nasal spray at a dosage of 2 sprays/nostril once daily. This randomized, double
      blind, placebo-controlled study was conducted in subjects with moderate-to-severe
      seasonal allergic rhinitis (SAR) during the 2007/2008 Texas Mountain Cedar
      season. In total, 536 subjects were randomized to 2 sprays/nostril once daily
      (A.M.) of azelastine 0.15% or placebo. The primary efficacy variable was change
      from baseline in a 12-hour reflective Total Nasal Symptom Score (TNSS),
      consisting of nasal congestion, runny nose, itchy nose, and sneezing. The key
      secondary variable was change from baseline in 24-hour instantaneous TNSS, which
      determines the duration of action and effective dosing interval. After 2 weeks,
      the mean improvement in 12-hour reflective TNSS and percentage improvement in 12
      hour reflective TNSS were significant (p < 0.001) with azelastine 0.15% (19%)
      compared with placebo (10%). The improvement in 24-hour instantaneous TNSS also
      was significant (p < 0.001) for azelastine 0.15% compared with placebo,
      supporting efficacy with once-daily dosing. All individual TNSS symptoms were
      significantly (p < 0.01) improved with azelastine 0.15% compared with placebo.
      With the exception of bitter taste (4.5%) and nasal discomfort (4.5%), adverse
      events with azelastine 0.15% were reported with an incidence similar to placebo.
      Azelastine 0.15% nasal spray was effective and well tolerated in subjects with
      SAR with once-daily dosing.

PMID- 19747430
TI  - The status of asthma control in the U.S. adult population.
AB  - Treatment guidelines recognize the importance of achieving and maintaining asthma
      control. This study was designed to assess the prevalence of asthma control in a
      representative U.S. population. A survey regarding asthma and associated symptoms
      was sent to a representative national sample of 134,401 households managed by the
      National Family Opinion WorldGroup from May to July 2007. Subjects >or=18 years
      with current asthma were identified and completed the Asthma Control Test (ACT),
      a brief validated self-administered survey that assesses asthma control. Subjects
      with an ACT score of >19 have been defined as having well-controlled asthma (WCA)
      and those with a score of <or=19 were defined as having not well-controlled
      asthma (NWCA). The prevalence of WCA was identified for the total population as
      well as subjects who currently were only using albuterol to control asthma
      symptoms. In addition, the frequency of past asthma exacerbations was studied and
      correlated with ACT. Surveys were returned by 81,505 households (61% return
      rate). A total of 10,139 adults self-reported having asthma and completed the
      ACT. Forty-one percent of these had NWCA and 39% of the subjects using albuterol
      as the only asthma medication had NWCA. Fifty-eight percent of subjects with NWCA
      in the total population had an asthma-related exacerbation (asthma-related oral
      corticosteroid use, emergency department, or hospitalization) in the previous
      year compared with 24% of subjects with WCA. This large representative national
      asthma sample using a validated asthma control instrument identified >40% of
      subjects with NWCA. In addition, subjects using albuterol monotherapy, who would
      be expected to have mild asthma and thus be well controlled, had a similar high
      prevalence of NWCA.

PMID- 19747431
TI  - Imaging the future: Does a qualitative analysis add to the picture?
AB  - Various studies report that patients with dense amnesia experience difficulties
      in simulating future events. It is argued that this resembles an inability to
      remember past episodes in that both indicate a deficit in mental scene
      construction. Such findings, however, rely upon quantitative content-based
      analyses of participants' verbal reports. Here, samples of verbal reports
      produced by participants with hippocampal lesions are subjected to a qualitative,
      discourse analysis of how participants and researchers negotiated the status of
      these reports. This shows that failure in mental scene construction can be viewed
      as an interactional achievement rather than the mere reporting of mental events.
      A multidisciplinary perspective which combines qualitative analysis with other
      forms of analytic technique may explain subtle differences between participants
      with hippocampal lesions and control participants.

PMID- 19747432
TI  - [Efficacy of arsenic trioxide for acute promyelocytic leukemia: a systematic
      review and meta-analysis].
AB  - OBJECTIVE: To systematically review the efficacy and safety of arsenic trioxide
      (ATO) in treatment of acute promyelocytic leukemia (APL). METHODS: The Cochrane
      Library (Issue 1, 2009), Cochrane Central Register of Controlled Trials (from
      1970 to January 2009), MEDLINE (from 1978 to October 2008), EMBASE (from 1950 to
      March 2009), Chinese Biological Medical Literature Database (from 1978 to
      December 2008), China National Knowledge Infrastructure (CNKI, from 1994 to
      December 2008), and China Medical Academic Conference Database (from 1994 to
      December 2008) were electronically searched. We also searched the Meta-Register
      of controlled trials, Conference Proceedings of American Society of Hematology
      (from 1946 to December 2008) and Conference Proceedings of American Society of
      Clinical Oncology (from 1946 to December 2008) on the internet for grey
      literature. The related journals in the library of Third Military Medical
      University were hand-searched. The randomized controlled trials (RCTs) of ATO in
      treatment of APL were included. We adopted complete remission, overall survival
      rate, disease free survival rate, time to complete remission, relapse rate,
      mortality and adverse reactions as outcome indicators. Data were entered and
      analyzed with the Cochrane review manager software 5.0 (RevMan 5.0). RESULTS:
      After merger of the included trials, five eligible RCTs with 328 cases were
      included. All the RCTs focused on the comparison of all-trans retinoic acid
      (ATRA) plus ATO regimen with ATRA monotherapy. Meta-analysis showed that the
      effect indexes for time to complete remission, two-year disease free survival
      rate, relapse rate, incidence of edema and incidence rate of QT interval
      prolongation were -1.20 [-1.68, -0.72], 8.64 [1.66,45.00], 0.21 [0.09,0.47], 4.16
      [1.46,11.79] and 22.10 [2.75,177.49], respectively. The influences on other
      outcome indicators such as complete remission and leukocytosis were statistically
      non-significant. CONCLUSION: ATO can prolong disease free survival and reduce the
      time to complete remission and relapse rate of newly diagnosed APL patients, and
      increase the incidence of edema and prolongation of corrected QT interval during
      the treatment. Due to limitation of the included trials, this conclusion needs to
      be validated by further studies.

PMID- 19747433
TI  - [Efficacy of Maxing Shigan Decoction combined with Western medicine for pneumonia
      in children: a systematic review and meta-analysis].
AB  - OBJECTIVE: To systematically evaluate the clinical effects of Maxing Shigan
      Decoction (MXSGD), a compound traditional Chinese herbal medicine, combined with
      Western medicine on pneumonia in children. METHODS: In this study, the relative
      trials published from 1994 to 2008 were searched in Chongqing Weipu Database,
      Chinese Journal Full-text Database, Wanfang database, Chinese Biomedical
      Literature Database and other electronic database by using the method of Cochrane
      systematic review. At the same time the information from related journals,
      professional data and network were hand-searched. The methodological quality of
      the included trials was assessed by two evaluators, and homogeneous evaluation by
      meta-analysis was performed. Statistical analysis of clinical data was performed
      by using RevMan 4.2.7 software provided by the Cochrane Collaboration. RESULTS: A
      total of 146 reports were found, while only eight randomized controlled trials
      met the inclusion criteria. The methodology quality of the reports included in
      the study was evaluated by the Jadad scale, and the specific random method,
      allocation concealment, blinding and intention-to-treat analysis were not
      described in all of the eight trial reports. As MXSGD combined with Western
      medicine group (treatment group) was compared with Western medicine group
      (control group), the meta-analysis indicated that the odds ratio for the total
      effective rate was 4.06, and the 95% confidence interval was from 2.63 to 6.27.
      MXSGD combined with Western medicine was good at increasing the total effective
      rate as compared with Western medicine, and the difference was statistically
      significant (P<0.000 01). CONCLUSION: MXSGD combined with Western medicine can
      improve clinical symptoms and increase the total effective rate of the patients
      with pneumonia in children. However, its clinical effects should be further
      identified by high quality, multicenter and randomized controlled trials with
      large-scale design.

PMID- 19747434
TI  - [Quantified diagnositic standard for large intestinal cancer of spleen qi
      deficiency syndrome.].
AB  - OBJECTIVE: To set a quantified diagnostic standard for large intestinal cancer of
      spleen qi deficiency syndrome. METHODS: The spleen qi deficiency syndrome was
      identified by experts on the basis of clinical epidemiological investigation of
      311 patients suffering from large intestinal cancer. Corresponding points were
      assigned to the correlative factors (traditional Chinese medicine symptoms) on
      the basis of symptom differences between spleen qi deficiency syndrome and non
      spleen-qi-deficiency syndrome. The best threshold was determined by receiver
      operating characteristic curve (ROC) according to syndrome differentiation from
      expert team, and the quantified diagnostic standard was established. The syndrome
      identification from the expert team which was regarded as golden standard was
      tested retrospectively. RESULTS: All the traditional Chinese medicine symptoms
      possibly related to spleen qi deficiency syndrome were analyzed based on the
      opinions of experts, and 28 symptoms were confirmed as candidate correlative
      factors. The occurrence of 11 symptoms between spleen qi deficiency syndrome and
      non-spleen-qi-deficiency syndrome showed statistical differences by means of
      crosstabs analysis (P<0.05). The 11 symptoms were filtered by logistic regression
      analysis, and tiredness, fatigue, loose stool, and poor appetite were finally
      determined as the symptoms relative to large intestinal cancer. These four
      symptoms were analyzed with conditional probability conversion and endowed with
      16, 11, 4 and 8 points respectively. The diagnostic standard of spleen qi
      deficiency syndrome of large intestinal cancer was over 13 points. The
      sensitivity, specificity and accuracy of retrospective examination were all above
      80%, and its positive likelihood ratio was 9.89. CONCLUSION: The quantified
      diagnostic standard for spleen qi deficiency syndrome of large intestinal cancer
      is in accordance with clinical characteristics of large intestine cancer and the
      characteristics of TCM syndrome diagnosis.

PMID- 19747435
TI  - [Tiaohe Ganpi Hexin Decoction in treatment of irritable bowel syndrome with
      diarrhea: a randomized controlled trial].
AB  - BACKGROUND: The quality of life has been greatly influenced and the cost of
      medical expenses is very high in patients with irritable bowel syndrome (IBS).
      The etiology and pathogenesis of IBS are still unclear, and the prevention and
      treatment of this disease still lack of effective methods. OBJECTIVE: To explore
      and analyze the effects of Tiaohe Ganpi Hexin Decoction (TGHD), a compound
      traditional Chinese herbal medicine for regulating the liver and spleen, on IBS
      patients with diarrhea. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: All 40
      IBS patients came from the First Hospital of Jinan University, Guangzhou Red
      Cross Hospital, and the First Affiliated Hospital of Guangzhou University of
      Chinese Medicine, and were randomly divided into two groups. Patients in the
      treatment group (n=20) were given TGHD, while those in the control group (n=20)
      were prescribed oral pinaverium with a four-week treatment period. MAIN OUTCOME
      MEASURES: Traditional Chinese medicine (TCM) syndrome score, total obviously
      effective rate, disappearance rate of symptoms, and clinical symptom score in the
      two groups were evaluated before and after four-week treatment. RESULTS: After
      the treatment, TCM syndrome scores in both groups were decreased (P<0.01), and
      the TCM syndrome score in the treatment group was significantly lower than that
      in the control group (P<0.01). There was a significant difference in the total
      obviously effective rate between the two groups (P<0.01), and the total obviously
      effective rates in the treatment and control groups were 85%(17/20) and 45%(9/20)
      respectively. The disappearance rates of abdominal pain, abdominal distention,
      poor stool output, stool frequency, stool character and mucous stool in the
      treatment group were higher than those in the control group (P<0.05). The symptom
      scores of abdominal pain, abdominal distention, poor stool output, stool
      frequency, stool character and mucous stool in the treatment group were lower
      than those in the control group (P<0.05). CONCLUSION: TGHD can significantly
      improve the clinical symptoms in IBS patients with diarrhea.

PMID- 19747436
TI  - [Traditional Chinese medicine diagnosis and treatment of type 2 diabetes in
      Tianjin urban population].
AB  - OBJECTIVE: To explore the traditional Chinese medicine (TCM) diagnosis and
      treatment of type 2 diabetes in Tianjin urban population. METHODS: A cross
      sectional study was conducted on hospital patients with type 2 diabetes in TCM
      hospitals of different levels in Tianjin from 2003 to 2007. The multiphasic
      stratified cluster sampling method was adopted in selecting the target hospital.
      Finally 3,496 patients were selected as the survey sample. Then the constituent
      ratios of diabetes in different syndrome types were calculated. RESULTS: In this
      study, the descending sort proportion of TCM syndrome types of type 2 diabetes in
      Tianjin urban population was deficiency of both qi and yin, stagnation of phlegm
      dampness, exuberant heat due to yin deficiency, deficiency of both yin and yang,
      and blood stasis and qi stagnation. Most of the diabetes patients with deficiency
      of both qi and yin, deficiency of both yin and yang, and stagnation of phlegm
      dampness were older than 60 years. Most of the diabetes patients with exuberant
      heat due to yin deficiency were 50 to 59 years old, while the diabetes patients
      with blood stasis and qi stagnation were 40 to 49 years old. The frequency of
      Danggui (Angelica sinensis) use was high in the diabetes patients with deficiency
      of both qi and yin; the frequency of Chenpi (Citrus reticulate Blanco) use was
      high in the diabetes patients with exuberant heat due to yin deficiency; the
      frequency of Baishao (Radix Paeoniae Alba) use was high in the diabetes patients
      with deficiency of both qi and yin; the frequency of Gancao (Radix Glycyrrhizae)
      use was high in the diabetes patients with stagnation of phlegm-dampness; and the
      frequency of Xingren (Semen Armeniacae) use was high in the diabetes patients
      with blood stasis and qi stagnation. CONCLUSION: The main syndrome types of
      diabetes patients in Tianjin urban area are deficiency of both qi and yin,
      stagnation of phlegm-dampness and exuberant heat due to yin deficiency. And the
      patients are mainly older than 50 years. The most frequently used herbs are
      Danggui (Angelica sinensis), Chenpi (Citrus reticulate Blanco), Baishao (Radix
      Paeoniae Alba), Gancao (Radix Glycyrrhizae) and Xingren (Semen Armeniacae).

PMID- 19747437
TI  - [Epidemiological investigation of perimenopausal women in Shanghai].
AB  - OBJECTIVE: To explore the cognitive level and the mental status of the patients
      suffering from perimenopausal syndrome in Shanghai, and to identify the
      traditional Chinese medicine syndrome distribution feature of perimenopausal
      syndrome. METHODS: The cognitive level of the perimenopausal women was evaluated
      by using general living problem questionnaire. The mental status of the
      perimenopausal women was evaluated by using self-rating depressive scale. The
      traditional Chinese medicine syndrome distribution feature of perimenopausal
      syndrome was identified by using traditional Chinese medical symptoms
      questionnaire. RESULTS: A total of 634 perimenopausal women finished the
      investigation. There were 74.76% (474/634) patients who knew little about the
      perimenopausal syndrome; 77.29% (490/634) patients had a depressive tendency;
      8.36% (53/634) patients had depressive disorder. There were 72.40% (459/634)
      patients who had the symptoms such as susceptibility to anger and restlessness,
      restless sleep at night, thirst with dry throat and bitter taste, and all these
      symptoms could be classified into hyperactivity of heart and liver fire syndrome.
      CONCLUSION: Patients suffering from perimenopausal syndrome know little about
      this disease and mostly have depressive tendency, and the major traditional
      Chinese medicine syndrome pattern is hyperactivity of heart and liver fire based
      on the chief clinical manifestations of the patients.

PMID- 19747438
TI  - [Effects of intratumoral injection of microspheres containing cobra venom
      cytotoxin on transplanted human hepatoma in nude mice].
AB  - OBJECTIVE: To evaluate the safety and efficacy of intratumoral injection of
      polylactic-co-glycolic acid (PLGA) microspheres containing cobra venom cytotoxin
      in nude mice with transplanted human hepatoma. METHODS: Cytotoxic activity of
      cytotoxin from cobra venom was determined by using methyl thiazolyl tetrazolium
      method in vitro. Microspheres containing cobra venom cytotoxin were prepared with
      a double emulsion-solvent evaporation method. Forty BALB/c nude mice were
      inoculated subcutaneously in right flank with hepatoma BEL-7404 cells. Thirty-two
      mice whose tumor size reached about 1.0 cm in diameter, were randomly assigned
      into normal saline group, blank microsphers group, cytotoxin group and cytotoxin
      PLGA group. Nude mice were intratumorally injected with normal saline, blank
      microspheres, cytotoxin or cytotoxin-PLGA microspheres respectively. Internal
      echo characteristics and blood flow of tumors were observed by high-frequency
      ultrasound every week after treatment. Twenty-six days after treatment, the
      tumors were removed to calculate the inhibition rate of tumor growth. The tumor,
      heart, liver and kidney tissues were obtained for histopathological examination.
      RESULTS: The cytotoxin separated and purified from crude cobra venom caused
      intense cytotoxic effects to the BEL-7404 cells in vitro. The diameter of PLGA
      microspheres containing cobra venom cytotoxin was about (34.45+/-9.85)microm.
      Encapsulation rate was up to (78.13+/-8.92)%, and cumulative amount of cobra
      venom cytotoxin released from the PLGA microspheres in vitro during 30 days was
      up to 84.3%. After intratumoral injection, tumor volumes and weights in the
      cytotoxin-PLGA group were lower than those in the normal saline group, with a
      tumor growth inhibition rate of 52.36%. Observed under a light microscope, most
      tumor tissues were necrotic. No obvious morphological change could be seen on the
      liver, kidney and heart tissues. CONCLUSION: The above findings indicate that
      intratumoral injection of cytotoxin-PLGA microspheres has strong antitumor effect
      and can obviously lessen systemic toxicity, which may provide an effective and
      feasible method for hepatocellular carcinoma treatment.

PMID- 19747439
TI  - [Effects of extracts and active components of Rhizoma Coptidis on contraction of
      circular smooth muscle isolated from guinea pig gastric antrum].
AB  - OBJECTIVE: To identify the influence of extracts and active components of Rhizoma
      Coptidis on gastric smooth muscle contractility of guinea pigs, and to explore
      the potential pharmacological mechanism of Rhizoma Coptidis in "invigorating the
      stomach" and "impairing the stomach". METHODS: Observing the effects of the water
      extract and the alkaloids from Rhizoma Coptidis (at doses ranging from 0.3 to
      1,000 microg/L) and other active components such as berberine, palmatine and
      jatrorrhizine (at doses ranging from 0.3 to 1,000 micromol/L) on the spontaneous
      and electrical field stimulation (EFS)-induced contractions of antral circular
      smooth muscle strips from guinea pig stomach via a force transducer in vitro.
      RESULTS: The water extract or the alkaloids from Rhizoma Coptidis could improve
      the spontaneous contraction at the low doses, but inhibit the spontaneous
      contraction at the high doses. Berberine, palmatine and jatrorrhizine also showed
      the similar effects. Moreover, the water extract and the alkaloids of Rhizoma
      Coptidis, as well as berberine, palmatine and jatrorrhizine could increase the
      EFS-induced contraction. Among the three monomers, jatrorrhizine exhibited the
      most potent effect on EFS-induced contraction. CONCLUSION: The effects of Rhizoma
      Coptidis in "invigorating the stomach" or "impairing the stomach" may be related
      to its effect on gastric smooth muscle contractility. Berberine, palmatine and
      jatrorrhizine are all effective components of Rhizoma Coptidis affecting the
      contraction of gastric smooth muscle, among which jatrorrhizine is the most
      potent agent in promoting the contraction while berberine is the most potent one
      for inhibiting the contraction.

PMID- 19747440
TI  - [Changes of mitochondrial apoptosis in spinal cord ischemia-reperfusion injury
      and the effects of Herba Erigerontis Breviscapi Injection preconditioning
      intervention in rabbits].
AB  - OBJECTIVE: To investigate the mechanisms of mitochondrial apoptosis in spinal
      cord ischemia-reperfusion injury and the effects of Herba Erigerontis Breviscapi
      Injection preconditioning intervention. METHODS: Sixty Japanese rabbits were
      divided into sham-operated group, ischemia group, ischemia-reperfusion group (1,
      6, 24 and 48 h), and Herba Erigerontis Breviscapi Injection group (1, 6, 24 and
      48 h). Clamping the abdominal aorta was used to construct the rabbit model of
      spinal cord ischemia-reperfusion injury. The rabbits in the ischemia-reperfusion
      group and the Herba Erigerontis Breviscapi Injection group underwent reperfusion
      for 1, 6, 24, 48 h respectively after fifty-minute ischemia. The rabbits in the
      Herba Erigerontis Breviscapi Injection group were administered with Herba
      Erigerontis Breviscapi Injection at 9 mg/kg 30 minutes before ischemia. Rate of
      apoptotic cells was measured by flow cytometry; contents of caspase-9 and
      apoptosis-inducing factor (AIF) in cytoplasm and serum were measured by enzyme
      linked immunosorbent assay. RESULTS: Compared with the sham-operated group and
      the ischemia group, the rates of apoptotic cells, the contents of caspase-9 and
      AIF in cytoplasm were increased at all time points after reperfusion, and the
      contents of caspase-9 and AIF in serum were decreased after 1 h and 6 h
      reperfusion, and increased after 24 h and 48 h reperfusion in the ischemia
      reperfusion group. Herba Erigerontis Breviscapi Injection intervention could
      decrease the rate of apoptotic cells and the contents of caspase-9 and AIF in
      cytoplasm and serum as compared with those in the ischemia-reperfusion group, and
      the effects appeared after 1 h reperfusion. CONCLUSION: The apoptosis of nerve
      cells after spinal cord ischemia-reperfusion is related to the mitochondrial
      pathways. Herba Erigerontis Breviscapi Injection can inhibit nerve cell apoptosis
      by decreasing the contents of caspase-9 and AIF in cytoplasm and serum.

PMID- 19747441
TI  - [Effects of Qichu Fujin Recipe on regeneration and repair of injured sciatic
      nerve in rats].
AB  - OBJECTIVE: To explore the effects of Qichu Fujin Recipe (QCFJR), a compound
      traditional Chinese medicine, in repairing sciatic nerve injury in rats. METHODS:
      A total of 60 male Sprague-Dawley (SD) rats were randomly divided into four
      groups: normal control group, untreated group, mecobalamin group and QCFJR group.
      Except the normal control group, sciatic nerve injury was induced by crushing of
      left sciatic nerve. Rats in the mecobalamin group were intragastrically
      administered with mecobalamin solutions 150 microg/(kg x d), and rats in the
      QCFJR group were intragastrically administered with QCFJR 35.2 g/(kg x d), while
      rats in the untreated group were intragastrically administered with normal saline
      (0.5 mL/d), once a day for 4 weeks respectively. Sciatic function index (SFI) was
      determined by walking tract analysis 1 week and 2 and 4 weeks after crushing.
      Five rats in each group were sacrificed for histological observation at the
      different time points. The remnant rate of gastrocnemius wet weight and the
      diameter of gastrocnemius cells were calculated. Expression of S-100 protein in
      the distal stump of injured nerve was observed by using immunohistochemical
      method. Distal injured sciatic nerves were determined with toluidine blue
      staining and observed under a light microscope 1 week and 2 and 4 weeks after
      operation. Diameter of axon and depth of myelin sheath were calculated by an
      image analysis system. Ultrastructure of nerve fibers was determined with uranyl
      acetate and lead citrate staining and observed under an electron microscope.
      RESULTS: Compared with the normal control group, SFI, remnant rate of
      gastrocnemius wet weight, diameter of gastrocnemius cells, expression of S-100,
      diameter of axon and depth of myelin sheath in the mecobalamin group and the
      QCFJR group were significantly decreased at different time points (P<0.05),
      superior to those of the untreated group (P<0.05, P<0.01). Except the remnant
      rate of gastrocnemius wet weight and the diameter of gastrocnemius cells, there
      were no significant differences in other indexes between the mecobalamin group
      and the QCFJR group 1 week and 2 and 4 weeks after crushing (P>0.05). CONCLUSION:
      QCFJR can stimulate the regeneration and repair of nerve fiber and delay the
      skeletal muscle atrophy after sciatic nerve injury in rats.

PMID- 19747442
TI  - [Effects of Ruanmailing Oral Liquid on spatial learning and memory ability and
      expression of APE/Ref-1 in hippocampal CA1 region in rats with experimental
      vascular dementia].
AB  - OBJECTIVE: To study the effects of Ruanmailing Oral Liquid, a compound
      traditional Chinese herbal medicine, on spatial learning and memory ability and
      expression of apurinic/apyrimidinic endonuclease/redox factor-1 (APE/Ref-1) in
      hippocampal CA1 region in rats with experimental vascular dementia (VaD).
      METHODS: VaD was induced in rats by permanent occlusion of bilateral common
      carotid arteries. Forty-five VaD rats were randomly divided into untreated group,
      nimodipine group, low-dose Ruanmailing group and high-dose Ruanmailing group.
      Another 15 rats underwent a sham operation consisting of similar skin incision
      and manipulation but without occlusion of carotid arteries. From the next day
      after occlusion, the rats were intragastrically administered with normal saline,
      nimodipine suspension or Ruanmailing Oral Liquid respectively for 30 days. Morris
      water maze experiment was adopted to test learning and memory of rats in each
      group. Expression of APE/Ref-1 protein in the hippocampal CA1 region was measured
      by immunohistochemical method. RESULTS: Escape latency was significantly
      shortened and number of entries in the target area of rats was significantly
      increased in the high-dose Ruanmailing group as compared with those in the
      untreated group (P<0.01). Compared with the untreated group, count of APE/Ref-1
      positive cells was significantly increased in the hippocampal CA1 region in the
      high- and low-dose Ruanmailing groups (P<0.01). Compared with the low-dose group
      and the nimodipine group, the count of APE/Ref-1 positive cells was remarkably
      increased in the hippocampal CA1 region in rats of the high-dose Ruanmailing
      group (P<0.01). There was no statistical difference between the low-dose
      Ruanmailing group and the nimodipine group. CONCLUSION: Ruanmailing Oral Liquid
      can improve the learning and memory ability and enhance the lowered expression
      level of APE/Ref-1 in the hippocampal CA1 region of rats with VaD.

PMID- 19747443
TI  - [Effects of Naomaitong combined with mobilization of bone marrow mesenchymal stem
      cells on neuron apoptosis and expressions of Fas, FasL and caspase-3 proteins in
      rats with cerebral ischemia].
AB  - OBJECTIVE: To observe the effects of Naomaitong, a compound traditional Chinese
      herbal medicine, combined with mobilization of bone marrow mesenchymal stem cells
      (BMSCs) on neuron apoptosis in rats with cerebral ischemia, and to explore the
      possible mechanism by detecting the expressions of Fas, FasL and caspase-3
      proteins. METHODS: Two hundred and two SD rats were divided into sham-operated
      group, untreated group, recombinant granulocyte colony-stimulating factor (rG
      CSF) group, Naomaitong group and Naomaitong plus rG-CSF group (combination
      group). Focal cerebral ischemia was induced by intraluminal middle cerebral
      artery occlusion using a nylon thread with some modification. Rats in the rG-CSF
      group and the untreated group were administered with rG-CSF 10 microg/(kg x d) by
      subcutaneous injection 3 d before and 2 d after the operation respectively, once
      a day, and rats in the Naomaitong group and the combination group were
      intragastrically administered Naomaitong before and after the operation until
      sacrificed. Two, three, seven and fourteen days after operation, count of CD34
      positive cells in peripheral blood and CD34 expression in brain tissue were
      determined. General neural function score (GNFS) was evaluated. Neuron apoptosis,
      expressions of Fas, FasL and caspase-3 in rat's brain were all measured. RESULTS:
      Count of CD34-positive cells in peripheral blood and CD34 expression in brain
      tissue were high in the untreated group, and reached the peak at 3 d and 7 d
      respectively. CD34 expression in brain tissue was increased in each treated
      group, especially in the combination group. GNFS was increased at 3 d and 7 d in
      the untreated group, 7 d and 14 d in the rG-CSF group and the combination group.
      Expressions of Fas, FasL and caspase-3 were increased 2, 3 and 7 d after
      operation, while expression of FasL at 2 d in the rG-CSF group, expressions of
      Fas, FasL and caspase-3 in the combination group were decreased. Expressions of
      Fas, FasL and caspase-3 at 7 d and 14 d in the combination group were lower than
      those in the rG-CSF group. Meanwhile, expressions of Fas, FasL and caspase-3 were
      decreased in each group at 14 d as compared with those at 3 d. CONCLUSION: There
      exists interaction between Naomaitong and BMSC mobilization in the effect of
      improving nerve function and inhibiting neuron apoptosis in rats after cerebral
      ischemia. It is implied that Naomaitong combined with BMSC mobilization down
      regulates the expressions of Fas and FasL in early phase and then inhibits the
      apoptosis cascade reaction caused by caspase-3, which causes further inhibition
      of Fas and FasL expression after cerebral ischemia.

PMID- 19747444
TI  - [Effects of ranitidine on pharmacokinetics of rhein from Dachengqi Decoction in
      rats after oral administration].
AB  - OBJECTIVE: To explore the effects of ranitidine on pharmacokinetics of rhein in
      rats after oral administration of Dachengqi Decoction (DCQD), a compound
      traditional Chinese herbal medicine. METHODS: Twelve male Sprague-Dawley rats
      were divided into DCQD group and DCQD plus ranitidine group, and were orally
      administered with DCQD at a dose of 10 g/kg or DCQD (10 g/kg) combined with
      ranitidine (150 mg/kg), respectively. Blood samples were gathered after a series
      of time intervals. Metabolism of rhein was determined with a reversed-phase high
      performance liquid chromatography with internal standard of 1, 8
      dihydroxyanthraquinone and the data were analyzed with DAS 2.1 program. The
      pharmacokinetic parameters were compared between the two groups. RESULTS: The
      pharmacokinetic parameters of rhein in the DCQD group, including peak
      concentration (C(max)), area under the plasma concentration-time curve (AUC),
      distribution phase half-life (t(1/2alpha)), elimination rate constant (K(10)) and
      central to peripheral transfer rate constant (K(12)), were significantly
      different to those in the DCQD plus ranitidine group (P<0.05, P<0.01). There were
      no significant differences in the other parameters between the two groups.
      CONCLUSION: Ranitidine can influence the pharmacokinetics of rhein in rats after
      oral administration of DCQD.

PMID- 19747445
TI  - [Current status of traditional Chinese medicine therapy in treating tumor
      cachexia].

PMID- 19747446
TI  - [Statistical analysis using SAS software package for data of RxC contingency
      table (Part two)].

PMID- 19747447
TI  - Comparative study on WHO Western Pacific Region and World Federation of Chinese
      Medicine Societies international standard terminologies on traditional medicine:
      an analysis of the Diagnostics (Part 1).

PMID- 19747448
TI  - Footnote: a compensating approach for translating and introducing Taoist medical
      jargon.

PMID- 19747450
TI  - [National research center in complementary and alternative medicine:University of
      Tromso, Norway].

PMID- 19747451
TI  - An unusual dependence of human herpesvirus-8 glycoproteins-induced cell-to-cell
      fusion on heparan sulfate.
AB  - Human herpesvirus-8 (HHV-8) is known to interact with cell surface heparan
      sulfate (HS) for entry into a target cell. Here we investigated the role of HS
      during HHV-8 glycoproteins-induced cell fusion. Interestingly, the observed
      fusion demonstrated an unusual dependence on HS as evident from following lines
      of evidence: (1) a significant reduction in cell-to-cell fusion occurred when
      target cells were treated with heparinase; (2) in a competition assay, when the
      effector cells expressing HHV-8 glycoproteins were challenged with soluble HS,
      cell-to-cell fusion was reduced; and, (3) co-expression of HHV-8 glycoproteins gH
      gL on target cells resulted in inhibition of cell surface HS expression. Taken
      together, our results indicate that cell surface HS can play an additional role
      during HHV-8 pathogenesis.

PMID- 19747452
TI  - Assembly of an intact Golgi complex requires phospholipase A2 (PLA2) activity,
      membrane tubules, and dynein-mediated microtubule transport.
AB  - Previous studies have shown that treatment of mammalian cells with phospholipase
      A(2) (PLA(2)) antagonists cause the normally interconnected Golgi ribbon to break
      up into large fragments of stacked Golgi cisternae ("mini-stacks") that remain
      located in the juxtanuclear region. Using the reversible PLA(2) antagonist, ONO
      RS-082 (ONO) and live-cell, time-lapse microscopy to image the Golgi reassembly
      process, we found that Golgi mini-stacks underwent a burst of membrane tubule
      formation following washout of ONO: before washout only 4.3+/-3.8 tubules/cell/10
      min were formed, whereas after washout 29.9+/-11.9 tubules/cell/10 min formed.
      These membranes tubules formed bridges between physically separate mini-stacks,
      thus mediating their coalescence into intact Golgi ribbons. Formation of inter
      stack tubules and an intact Golgi ribbon was also facilitated by microtubules
      because treatment with nocodazole significantly inhibited both processes. This
      microtubule-dependent process was also dependent on dynein because the dynein
      inhibitor nordihydroguaiaretic acid (NDGA) inhibited reassembly. These studies
      show that a late stage of Golgi assembly occurs via membrane tubules, whose
      formation is dependent on PLA(2) activity and microtubules. Considering these
      results together, we concluded that the maintenance and assembly of normal Golgi
      architecture is dependent on the PLA(2)-mediated, dynamic formation of inter
      Golgi membrane tubules.

PMID- 19747453
TI  - L-Serine-O-phosphate in the central nervous system.
AB  - L-serine-O-phosphate (L-SOP) is the immediate precursor to L-serine in the serine
      synthesis pathway and is also an agonist at the Group III metabotropic glutamate
      receptors (mGluRs). L-SOP is produced by the enzyme phosphoserine
      aminotransferase (PSAT) and metabolized to L-serine by phosphoserine phosphatase
      (PSP). Using a novel analytical procedure, we show that L-SOP is present in rat
      whole brain, and that in transfected cells, it is substantially more potent than
      L-glutamate at the mGluR4 receptor subtype. Immunocytochemical analyses showed
      that the distributions of PSAT and PSP in the cerebral cortex, hippocampus, and
      cerebellum were similar in the rat and macaque monkey brain. In the rat
      hippocampus, cells within the subgranular zone were co-labeled with anti-PSP and
      anti-PSA-NCAM, a marker for neurogenic cells. In the cerebellar cortex, Purkinje
      neurons expressed relatively high levels of both enzymes while robust expression
      of PSAT was also observed in the Bergmann glia. L-SOP released from Purkinje
      neurons or Bergmann glia could activate mGluR4 present on parallel fiber
      terminals. The presence of l-SOP in brain, its high potency at mGluR4, together
      with the restricted distributions of the synthetic and metabolic enzymes, suggest
      that L-SOP might act activate Group III metabotropic glutamate receptors in the
      CNS.

PMID- 19747454
TI  - Repeated preconditioning with hyperbaric oxygen induces neuroprotection against
      forebrain ischemia via suppression of p38 mitogen activated protein kinase.
AB  - We previously reported in rats that preconditioning with hyperbaric oxygen (HBO;
      100% O(2) 3.5-atomsphere absolute (ATA), 1 h/day for 5 days) provided
      neuroprotection against transient (8 min) forebrain ischemia possibly through
      protein synthesis relevant to neurotrophin receptor and inflammatory-immune
      system. A recent report suggested that HBO-induced neuroprotection is relevant to
      brain derived neurotrophic factor and its downstream event involving suppression
      of p38 mitogen activated protein kinase (p38) activation. In the present study,
      we first performed a dose comparison (1, 2, and 3.5 ATA) of HBO-induced
      neuroprotection and then investigated pharmacological modification by 10 mg/kg
      anisomycin (a protein synthesis inhibitor and potent activator for p38) and 200
      microg/kg SB203580 (a p38 inhibitor), which were given intraperitoneally 60 and
      30 min before every 3.5 ATA-HBO treatment, respectively. Most prominent
      protective effect on hippocampal CA1 neurons was observed with 3.5 ATA-HBO
      (survived neurons: 69% [62-73%] vs. untreated: 3.9% [2-8%], 1 ATA: 8.8% [0-26%],
      2 ATA-HBO: 46% [22-62%] (median [range]) (7 days after ischemia). Anisomycin
      abolished a neuroprotective effect (survived neuron: 1.2% [0-7%]). SB203580, when
      given between administration of anisomycin and HBO treatment, resumed a
      neuroprotective effect (survived neuron: 52% [37-62%]). The level of
      phosphorylated p38 at 10-min reperfusion was significantly decreased in 3.5 ATA
      HBO group (32% [12-53%] of sham). Single pretreatment with 100 and 200 microg/kg
      of SB203580 exerted a similar neuroprotective effect (39% [25-51%] and 59% [50
      72%]) to 2 and 3.5 ATA-HBO preconditioning, respectively. It is concluded that
      suppression of p38 phosphorylation plays a key role in HBO-induced
      neuroprotection and that pretreatment with a p38 inhibitor (SB203580) can provide
      similar neuroprotection.

PMID- 19747455
TI  - Visual cues release the temporal coherence of auditory objects in auditory scene
      analysis.
AB  - Auditory scene analysis can arrange alternating tones of high and low pitch in a
      single, integrated melody, or in two parallel, segregated melodies, depending on
      the presentation rate and pitch contrast of the tones. We conducted an
      electrophysiological experiment to determine whether an inherently stable sound
      organization can be altered by a synchronous presentation of visual cues. To this
      end, two tones with different frequencies were presented in alternation.
      Frequency distance was selected as narrow or wide, inducing an inherently stable
      integrated or segregated organization, respectively. To modulate the integration
      or segregation organization, visual stimuli were synchronized to either the
      within-set frequency pattern or with a superimposed intensity pattern. Occasional
      deviations of the regular frequency pattern were introduced. Elicitation of the
      mismatch negativity (MMN) component of event-related brain potentials by these
      deviants indexed the presence of a segregated organization. MMN was elicited by
      tone sequences with wide frequency distance irrespective of the presence of
      visual cues. At a narrow frequency distance, however, an MMN was elicited when
      the visual pattern promoted segregation of the sounds showing a release of the
      inherently stable integrated organization due to visual stimulation. The results
      demonstrate cross-modal effects on auditory object perceptual organization even
      on an inherently stable auditory organization.

PMID- 19747456
TI  - Descending glutamatergic pathways of PFC are involved in acute and chronic action
      of methylphenidate.
AB  - Progressive augmentation of behavioral response following repeated
      psychostimulant administrations is known as behavioral sensitization, and is an
      indicator of a drug's liability for abuse. It is known that methylphenidate (MPD)
      (also known as Ritalin), a drug used to treat attention-deficit hyperactivity
      disorder (ADHD), induces sensitization in animals following repeated injections.
      It was recently reported that bilateral electric (non-specific) lesion of
      prefrontal cortex (PFC) prevented MPD elicited behavioral sensitization. Since
      PFC sends glutamatergic afferents to both ventral tegmental area (VTA) and
      nucleus accumbens (NAc), sites that are involved in induction and expression of
      behavioral sensitization respectively and glutamate from PFC is known to modulate
      dopamine cell activity in VTA and NAc, this study investigated the role of
      descending glutamate from PFC in MPD elicited behavioral sensitization. Locomotor
      activity of three groups of rats-control, sham operated and group with specific
      chemical lesion of glutamate neurons of PFC-was recorded using an open-field
      assay. On experimental day (ED) 1, the locomotor activity was recorded post a
      saline injection. The sham and lesion groups underwent respective surgeries on ED
      2, and were allowed to recover for 5 days (from ED 3 to ED 7). The post-surgery
      baseline was recorded on ED 8 following a saline injection. On ED's 9 through 14,
      2.5 mg/kg MPD was given, followed by a 4-day washout period (ED 15 -18). All
      three groups received a rechallenge injection of 2.5 mg/kg on ED 19 and their
      locomotor activity on various days was analyzed. It was found that ibotenic acid
      lesion modulated the acute and chronic effects of MPD and hence suggests that PFC
      glutamatergic afferents are involved in the acute effect of MPD as well as in its
      chronic effects such as behavioral sensitization to MPD.

PMID- 19747457
TI  - Non-NMDA receptors in the lateral parabrachial nucleus modulate sodium appetite.
AB  - Glutamatergic mechanisms have been implicated in the control of fluid ingestion.
      In the present study, we investigated whether non-N-methyl-d-aspartate (NMDA)
      glutamatergic receptors in the lateral parabrachial nucleus (LPBN) are involved
      in the control of water and sodium intake. Male Sprague-Dawley rats had cannulas
      implanted bilaterally into the LPBN. They were acutely depleted of water and
      sodium by injections of the diuretic furosemide (Furo; 10 mg/kg, bw) and given a
      low dose of the angiotensin-converting enzyme inhibitor, captopril (Cap; 5 mg/kg,
      bw). Bilateral LPBN injections of the non-NMDA receptor antagonist DNQX (2 and 5
      nmol/0.2 microl) increased the ingestion of 0.3 M NaCl and water of Furo/Cap
      treated rats. The increased ingestion produced by DNQX was abolished by
      pretreating the LPBN with alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic
      acid (AMPA), a non-NMDA receptor agonist. AMPA injected alone into the LPBN
      reduced water and 0.3 M NaCl intake. Injections of DNQX (5 nmol/0.2 microl) into
      the LPBN also produced ingestion of 0.3 M NaCl after sc injections of the beta
      adrenoceptor agonist, isoproterenol, a hypotensive drug that typically produces
      only water intake. Food intake, arterial blood pressure and heart rate were not
      altered by DNQX LPBN injections. We conclude that agonists acting on non-NMDA
      receptors in the LPBN exert an inhibitory influence on sodium intake during acute
      fluid depletion with hypotension and after isoproterenol treatment. A possible
      interaction of serotonin with glutamate within the LPBN is discussed.

PMID- 19747458
TI  - Simplified experimental cerebral aneurysm model in rats: comprehensive evaluation
      of induced aneurysms and arterial changes in the circle of Willis.
AB  - Establishing a simple and comprehensive experimental model is one of the most
      important issues in the study of cerebral aneurysms. Previous models in the rat
      required two stage surgeries and observations were limited to a few branching
      sites. The present study aimed to introduce a simplified model in rats and to
      provide a comprehensive evaluation of induced arterial changes in the circle of
      Willis. Sprague-Dawley rats underwent ligation of the right common carotid
      artery, and posterior and inferior (group 2, n=9) or only posterior (group 3,
      n=12) branches of the bilateral renal arteries, and bilateral oophorectomy. Dahl
      salt-sensitive rats underwent only carotid ligation and bilateral oophorectomy
      (group 5, n=11). All surgical procedures were completed in one procedure instead
      of two in the original method. Salt loading was started after the surgery. Five
      rats of each strain without treatment served as controls (groups 1 and 4,
      respectively). Three months later, vascular corrosion casts of the cerebral
      arteries were examined by scanning electron microscopy. Experimental rats in
      groups 2, 3, and 5 developed 43 aneurysmal lesions at branching sites. Forty
      eight arterial changes including dilatation, tortuosity, and fusiform or lateral
      wall aneurysms were observed at non-branching sites. Group 3 appeared to be
      superior to the other groups for experimental studies. The frequency and degree
      of the induced lesions were comparable with previous studies even after the
      surgical simplification. The present model may be more practical for the study of
      experimental cerebral aneurysms.

PMID- 19747459
TI  - Dexamethasone treatment of naive organ of Corti explants alters the expression
      pattern of apoptosis-related genes.
AB  - BACKGROUND: Dexamethasone treatment of organ of Corti explants challenged with an
      ototoxic level of an inflammatory cytokine modulates NFkappaB signaling and the
      expression levels of both pro-and anti-apoptosis-related genes. It is not known
      if naive organ of Corti explants will respond in a similar manner to treatment
      with a corticosteroid. This study examines the response of naive organ of Corti
      explants to treatment with dexamethasone. METHODS: Three-day-old rat organ of
      Corti explants were cultured for 1, 2, or 4 days. Four-day in vitro cultures were
      fixed, stained with FITC-phalloidin and hair cells were counted. ELISA was
      performed on 2-day cultures to determine the levels of phosphorylated nuclear
      factor kappa B protein. One- and 2-day cultures were studied with real-time RT
      PCR for expression levels of beta-actin, Bax, Bcl-xl, Bcl-2 and TNFR1 genes with
      mean fold changes determined with the 2(-)(DeltaDeltaCt) method. All mean fold
      changes in gene and protein expression were analyzed by the Kruskal-Wallis non
      parametric test. RESULTS: There were no significant differences in hair cell
      counts between naive explants and explants treated with dexamethasone.
      Dexamethasone treatment of naive explants resulted in a significant increase
      (p<0.01) in the level of phosphorylated-nuclear factor kappa B protein. Bax
      expression was significantly decreased (p<0.01) in the dexamethasone-treated
      explants compared to untreated-naive explants at 1 and 2 days. TNFR1 expression
      was significantly reduced in dexamethasone-treated explants at 1 (p<0.01) and 2
      days (p=0.001). Both Bcl-2 and Bcl-xl expression levels were significantly
      increased in dexamethasone-treated cultures compared to naive-cultures at 2 days
      in vitro (p<0.001). Dexamethasone-treated explants showed a significant decrease
      in the Bax/Bcl-2 ratio at both 1 (p=0.004) and 2 days (p<0.001) in vitro.

PMID- 19747460
TI  - Cardiovascular responses to intravenous injection of a novel isoindolin-1-one
      derivate in conscious rats.
AB  - An isoindolin-1-one derivate, JM-1232(-), was recently developed as a sedative
      and hypnotic agent with a strong affinity for the central benzodiazepine binding
      site of gamma-aminobutyric acid(A) (GABA(A)) receptors. The purpose of this study
      was to examine the effects of JM-1232(-) on the cardiovascular and sympathetic
      functions of conscious rats. We investigated the effect of JM-1232(-) on the mean
      arterial pressure (MAP), heart rate (HR), baroreflex activity, and plasma
      catecholamine levels in conscious rats. The intravenous (i.v.) administration of
      JM-1232(-) (0.1, 0.3, and 1.0 mg/kg/min) for 20 min decreased MAP and increased
      HR in intact rats. In sinoaortic denervated (SAD) rats, JM-1232(-) decreased MAP
      and HR. A decrease in MAP induced by JM-1232(-) was prevented by pre-treatment
      with hexamethonium and enhanced by SAD. An increase in HR induced by JM-1232(-)
      was prevented by pre-treatment with atropine, propranolol, or hexamethonium. A
      decrease in MAP and an increase in HR induced by JM-1232(-) were antagonized by
      co-administration of flumazenil. A high dose of JM-1232(-) decreased the plasma
      norepinephrine concentration, and a subdepressor dose of JM-1232(-) did not
      affect the baroreceptor reflex. These results show that the i.v. administration
      of JM-1232(-) decreased MAP mediated by benzodiazepine-GABA(A) receptors.

PMID- 19747461
TI  - Gender related differences in visual and auditory processing of verbal and
      figural tasks.
AB  - The aim of the present study was to investigate gender related differences in
      brain activity for tasks of verbal and figural content presented in the visual
      and auditory modality. Thirty male and 30 female respondents solved four tasks
      while their electroencephalogram (EEG) was recorded. Also recorded was the
      percentage of oxygen saturation of hemoglobin (%StO(2)) in the respondents'
      frontal brain areas with near-infrared spectroscopy (NIRS). The main findings of
      the study can be summarized as follows. (1) Most pronounced differences between
      males and females were observed for the factor modality-visual/auditory. (2)
      Gender related differences in neuroelectric brain responses could be observed
      during the solution of auditory and visual tasks; however, on the behavioral
      level only for the visual tasks did females display shorter reaction times than
      males. The ERP amplitudes of the early evoked gamma response, P1, and P3 were
      higher in females than males, whereas the N4 amplitude was higher in males than
      females. The differences were more noticeable in the visual modality. The NIRS
      showed a more bilateral involvement of the frontal brain areas in females as
      compared with a more left hemispheric frontal activity in males. In the task
      conditions an increase in right hemispheric activity in females was observed;
      however, this increase was less pronounced in the visual than the auditory
      domain, indicating a more lateralized processing of visual stimuli in females.
      Taken all together the results suggest that the females' visual event
      categorization process is more efficient than in males.

PMID- 19747462
TI  - Inactivating the middle cerebellar peduncle abolishes the expression of short
      latency conditioned eyeblinks.
AB  - The interposed nuclei (IN) of the cerebellum play a crucial role in the
      classically conditioned eyeblink circuit. It has previously been shown in well
      trained animals that injecting the IN with GABA(A) antagonists produces short
      latency conditioned responses (SLRs). The mechanism underlying SLR generation is
      not clear. According to one concept, SLRs originate in cerebellar nuclei in
      response to direct inputs from collaterals of mossy fibers. An alternate
      explanation is that SLRs are produced by extra-cerebellar circuits that are
      excited by increased tonic activity in cerebellar nuclei or by the combined
      action of inputs to cerebellar nuclei from mossy fiber collaterals and
      incompletely blocked Purkinje cells. In the present study, we examined whether
      cerebellar afferent axons in the middle cerebellar peduncle (MCP) participate in
      SLR expression. We hypothesized that if SLRs are evoked by the sensory mossy
      fiber input to the IN and cerebellar cortex, then blocking the MCP should abolish
      these responses. Well-trained animals, which had been implanted with dual
      injection cannulae in the left IN and the left MCP, were injected with gabazine
      (GZ) into the IN to produce SLRs followed by an injection of the sodium channel
      blocker tetrodotoxin (TTX) into the MCP. TTX infusions in the MCP suppressed both
      CRs and SLRs. These findings suggest that the expression of SLRs depends on both
      direct and cerebellar cortex-mediated sensory information from the mossy fiber
      system.

PMID- 19747463
TI  - Category expectation modulates baseline and stimulus-evoked activity in human
      inferotemporal cortex.
AB  - Expectation of locations and low-level features increases activity in
      extrastriate visual areas even in the absence of a stimulus, but it is unclear
      whether or how expectation of higher-level stimulus properties affects visual
      responses. Here, we used event-related functional magnetic resonance imaging
      (fMRI) to test whether category expectation affects baseline and stimulus-evoked
      activity in higher-level, category-selective inferotemporal (IT) visual areas.
      Word cues indicating an image category (FACE or HOUSE) were followed by a delay,
      then a briefly presented image of a face or a house. On most trials, the cue
      correctly predicted the upcoming stimulus. Baseline activity in regions within
      the fusiform face area (FFA) and parahippocampal place area (PPA) was modulated
      such that activity was higher during expectation of the preferred (e.g., FACE for
      FFA) vs. non-preferred category. Stimulus-evoked responses reflected an initial
      bias (higher overall activity) followed by increased selectivity (greater
      difference between activity to a preferred vs. non-preferred stimulus) after
      expectation of the preferred vs. non-preferred category. Consistent with the
      putative role of a frontoparietal network in top-down modulation of activity in
      sensory cortex, expectation-related activity in several frontal and parietal
      areas correlated with the magnitude of baseline shifts in the FFA and PPA across
      subjects. Furthermore, expectation-related activity in lateral prefrontal cortex
      also correlated with the magnitude of expectation-based increases in stimulus
      selectivity in IT areas. These findings demonstrate that category expectation
      influences both baseline and stimulus-evoked activity in category-selective
      inferotemporal visual areas, and that these modulations may be driven by a
      frontoparietal attentional control network.

PMID- 19747464
TI  - Expression of kinase interacting with stathmin (KIS, UHMK1) in human brain and
      lymphoblasts: Effects of schizophrenia and genotype.
AB  - Single nucleotide polymorphisms (SNPs) within the gene encoding the
      serine/threonine kinase KIS (Kinase Interacting with Stathmin, also known as
      UHMK1) have recently been associated with schizophrenia. As none of the disease
      associated SNPs are coding, they may confer susceptibility by altering some facet
      of KIS expression. Here we have characterised the cellular distribution of KIS in
      human brain using in situ hybridisation and immunohistochemistry, and quantified
      KIS protein and mRNA in two large brain series to determine if KIS expression is
      altered in schizophrenia or bipolar disorder or in relation to a schizophrenia
      associated SNP (rs7513662). Post-mortem tissue from the superior temporal gyrus
      of schizophrenia and control subjects, and also dorsolateral prefrontal cortex,
      anterior cingulate cortex, and cerebellum from schizophrenia, bipolar disorder,
      and control subjects were used. KIS expression was measured by quantitative PCR
      (mRNA) and immunoautoradiography (protein), and was also quantified by immunoblot
      in lymphoblast cell lines derived from schizophrenia and control subjects. Our
      results demonstrate that KIS is expressed in neurons, and its encoded protein is
      localised to the nucleus and cytoplasm. No difference in KIS expression was found
      between diagnostic groups, or in the lymphoblast cell lines, and no effect of
      rs7513662 genotype on KIS expression was found. Hence, these data do not provide
      support for the hypothesis that altered expression is the mechanism by which
      genetic variation of KIS may increase susceptibility to schizophrenia, nor
      evidence that KIS expression is altered in the disease itself, at least in terms
      of the parameters studied here.

PMID- 19747465
TI  - The ventrolateral upper cervical cell group in cat projects to all rostrocaudal
      levels of the periaqueductal gray matter.
AB  - The lateral ventral horn of the upper cervical (C(1-3vl)) cord in rat, cat and
      monkey contains many cells that project to the periaqueductal gray matter (PAG).
      Until now it was assumed that these cells only project to the ventrolateral part
      of the caudal PAG. Because the ventrolateral caudal PAG is involved in quiescence
      and hypotension, it was hypothesized that the C(1-3vl)-PAG projecting cells play
      a role in immobility behavior, possibly activated by neck muscle afferents.
      However, in the present anterograde and retrograde study in cat we showed that
      C(1-3vl) cells do not only target the caudal PAG, but terminate even more
      abundantly in the intermediate and rostral parts of the PAG. There, projections
      target the ventrolateral column, like in the caudal PAG, but also terminate in
      the lateral and dorsomedial columns. This finding, combined with the current,
      albeit limited, physiological data on C(1-3vl)-PAG and C(1-3vl)-thalamic
      projecting cells, sheds a new light on the possible functions of C(1-3vl) cells.
      It might be that the C(1-3vl) cells with complex response properties and large
      receptive fields have a relay function similar to cells in the dorsal column
      nuclei, lateral cervical or central cervical nucleus. Other C(1-3vl) cells might
      receive somatic or visceral input that was never tested before, or perhaps other
      input, like vestibular information. It might also be that these cells project to
      the more caudal cord to modulate visceral input, with ascending collaterals to
      more rostrally located structures, including mesencephalon and thalamus.

PMID- 19747466
TI  - Neonatal administration of a vaccine preservative, thimerosal, produces lasting
      impairment of nociception and apparent activation of opioid system in rats.
AB  - Thimerosal (THIM), an organomercury preservative added to many child vaccines is
      a suspected factor in pathogenesis of neurodevelopmental disorders. We examined
      the pharmacokinetics of Hg in the brain, liver and kidneys after i.m. THIM
      injection in suckling rats and we tested THIM effect on nociception. THIM
      solutions were injected to Wistar and Lewis rats in a vaccination-like mode on PN
      days 7, 9, 11 and 15 in four equal doses. For Wistar rats these were: 12, 48,
      240, 720, 1440, 2160, 3000 microg Hg/kg and for Lewis: 54, 216, 540 and 1080
      microg Hg/kg. Pharmacokinetic analysis revealed that Hg from THIM injections
      accumulates in the rat brain in significant amounts and remains there longer than
      30 days after the injection. At the 6th week of age animals were examined for
      pain sensitivity using the hot plate test. THIM treated rats of both strains and
      sexes manifested statistically significantly elevated pain threshold (latency for
      paw licking, jumping) on a hot plate (56 degrees C). Wistar rats were more
      sensitive to this effect than Lewis rats. Protracted THIM-induced hypoalgesia was
      reversed by naloxone (5 mg/kg, i.p.) injected before the hot plate test,
      indicative of involvement of endogenous opioids. This was confirmed by augmented
      catalepsy after morphine (2.5 mg/kg, s.c.) injection. Acute THIM injection to 6
      week-old rats also produced hypoalgesia, but this effect was transient and was
      gone within 14 days. Present findings show that THIM administration to suckling
      or adult rats impairs sensitivity to pain, apparently due to activation the
      endogenous opioid system.

PMID- 19747467
TI  - Exposure to nitrous oxide stimulates a nitric oxide-dependent neuronal release of
      beta-endorphin in ventricular-cisternally-perfused rats.
AB  - We have previously shown that the antinociceptive effect of nitrous oxide (N(2)O)
      in the rat hot plate test is sensitive to antagonism by antisera against the
      endogenous opioid peptide beta-endorphin. Moreover, N(2)O-induced antinociception
      is reduced by inhibition of nitric oxide (NO) production in the brain. To test
      the hypothesis that N(2)O might stimulate an NO-dependent neuronal release of
      beta-endorphin, we conducted a ventricular-cisternal perfusion with artificial
      cerebrospinal fluid (aCSF) in urethane-anesthetized Sprague-Dawley rats. Ten
      minute fractions of aCSF perfusate were collected from separate groups of room
      air-exposed rats, N(2)O-exposed rats, and L-NAME-pretreated, N(2)O-exposed rats;
      they were then analyzed for their content of NO metabolites and beta-endorphin.
      Compared to room air control, exposure to 70% N(2)O increased perfusate levels of
      the NO metabolites nitrite and nitrate as well as beta-endorphin. Pretreatment of
      rats with L-N(G)-nitro arginine methyl ester, an inhibitor of NO synthase,
      prevented the N(2)O-induced increases in nitrite, nitrate and beta-endorphin.
      These findings demonstrate in an in vivo rat model that N(2)O may stimulate an NO
      dependent neuronal release of beta-endorphin.

PMID- 19747468
TI  - Inhibition of cerebral ischemia/reperfusion-induced injury by adenovirus
      expressed C-terminal amino acids of GluR6.
AB  - GluR6 kainate receptor subunit is largely expressed in hippocampus of brain
      regions and plays an important role in brain ischemia/reperfusion-mediated
      neuronal cell death. Our previous researches have shown that cerebral
      ischemia/reperfusion could facilitate the assembly of GluR6 and postsynaptic
      density protein 95(PSD95) as well as mixed lineage kinase 3(MLK3) and further
      induce the activation of c-Jun NH2-terminal kinase 3(JNK3), leading to neuronal
      death of hippocampal CA1. Here, we show that over-expression of C-terminal amino
      acids of GluR6 can interrupt the combination of GluR6 with PSD95, inhibit the
      assembly of GluR6.PSD-95.MLK3 signaling module, suppress the activation of JNK3
      and the downstream signaling pathway. Thus, our results imply that over
      expression of C-terminal amino acids of GluR6 induce neuroprotection against
      ischaemic brain injury in rat hippocampal CA1 region via suppressing proapoptosis
      signaling pathways, which can be an experimental foundation for gene therapy of
      stroke.

PMID- 19747469
TI  - Gabapentin treatment improves motor coordination in a mice model of progressive
      ataxia.
AB  - No causal treatment of ataxias is available at the moment, and so symptomatic and
      disease-modifying therapies are regarded as a reliable possibility for this
      complex group of movement disorders. In order to explore possible pharmacological
      strategies aimed at interfering with ataxia development or progression, we used
      HCN1-/- mice. Mice carrying the deletion of the gene encoding for the voltage
      dependent K-channel (HCN1-/-) have a normal basic motor function, but impaired
      learning of the motor skills that enable mice to balance on the rotating rod. In
      this study we showed that the motor coordination impairment observed in HCN1-/-
      mice is paralleled by a decline of GABA content in the cerebellum. Treatment with
      the GABA mimetic gabapentin at prenatal age prevents full development of the
      ataxia symptom. This result could have implications for possible therapeutic
      strategies aimed at more effective coupling with ataxia in several neurological
      diseases in which this symptom develops and is prominent over time. In view of
      its long-lasting effect, it could be also considered as a disease-modifying drug.

PMID- 19747471
TI  - Mutation scanning of exon 20 of the BRCA1 gene by high-resolution melting curve
      analysis.
AB  - OBJECTIVES: 5382insC frameshift mutation along with 5331G>A (G1738R) missense
      mutation, both found in exon 20 of the BRCA1 gene, are relatively frequent among
      the Greek breast and ovarian cancer population (46%). Our goal was to develop a
      novel, reliable and rapid genotyping/scanning method for mutation detection of
      the exon 20 of the BRCA1 gene, using high-resolution melting curve analysis.
      DESIGN AND METHODS: The developed methodology was based on real-time PCR and high
      resolution melting curve analysis in the presence of LCGreen I dye. Two amplicons
      on the exon 20 of BRCA1 gene were designed (157 bp and 100 bp), one flanking the
      exon's boundaries, and one embracing the 5382insC mutation. Our methodology was
      first optimized and validated by using genomic DNA samples with the 5382insC and
      5331G>A (G1738R) mutations and wild-type. In total, the developed methodology was
      applied on 90 peripheral blood and 127 formalin-fixed paraffin-embedded breast
      tissue samples. RESULTS: Sensitivity studies with gDNA isolated from peripheral
      blood showed that mutated DNA could be reliably detected in the presence of wild
      type DNA at 5% and 0.5% ratio with the larger and the smaller amplicon,
      respectively. By using the developed methodology we successfully identified
      5382insC, 5331G>A and 5370C>T (R1751X) mutations, in genomic DNA isolated from
      peripheral blood samples and 5382insC mutation in two breast tumors, as verified
      by DNA sequencing. CONCLUSIONS: The combination of real-time PCR and high
      resolution melting curve analysis provides a cost-efficient, simple and rapid
      approach to successfully scan exon 20 of BRCA1 gene for these clinically
      important and frequent mutations.

PMID- 19747470
TI  - Gastric afferents project to the aldosterone-sensitive HSD2 neurons of the NTS.
AB  - The HSD2 (11-beta-hydroxysteroid dehydrogenase-type 2 enzyme) containing neurons
      of the nucleus tractus solitarius (NTS) become activated during low-sodium and
      high-aldosterone states such as hypovolemia. This response may be due to hormonal
      and/or neural signals. Hormonal signals may activate neurons in the area postrema
      that innervate the HSD2 neurons. The vagus nerve projects directly to the HSD2
      neurons and this could be another route whereby these neurons receive information
      about systemic sodium/aldosterone status. The peripheral sites of origin that
      contribute to this vagal projection remain unknown, and in the present study, we
      injected the transganglionic tracer, cholera toxin beta-subunit-horseradish
      peroxidase (CTb-HRP), into wall of various gastrointestinal organs (stomach,
      small and large intestine) or liver of rats. Confocal microscopy of brainstem
      sections stained by a double immunohistochemical procedure was used to analyze
      whether the HSD2 neurons received axonal contacts from specific gastrointestinal
      structures. The major source of afferents arose from the stomach, mainly from its
      pyloric antrum, but a weaker input originated from the fundus region. A trace
      amount originated from the duodenum. The terminal part of the small intestine and
      large intestine did not to contribute to this projection. Similarly, no afferent
      inputs from the liver or portal vein were found. In conclusion, HSD2 neurons
      receive an input mainly from the stomach and these results are considered as
      potential sites affecting sodium intake.

PMID- 19747472
TI  - Is the role of circulating DNA as a biomarker of cancer being prematurely
      overrated?
AB  - BACKGROUND: Circulating DNA is utilized widely as a genetic biomarker in a
      variety of pathological conditions, mainly in cancerous conditions.
      Quantification of circulating DNA and identifying the frequencies of a variety of
      mutations, microsatellite alterations and gene promoter methylation are the main
      foci of research on circulating DNA. CONTENT: A compilation of research reports
      available to us were reviewed to highlight the rather great variety of methods
      presently used to isolate circulating DNA, the lack of uniformity in presenting
      and interpreting quantitative research data as well as the virtual absence of
      information regarding the structure and function of circulating DNA. CONCLUSIONS:
      The information compelled us to conclude that the application of circulating DNA
      as an unambiguous biomarker is currently overrated. We therefore emphasize the
      need for elucidating the prevailing questions regarding the origin, function and
      significance of these nucleic acid molecules before utilizing circulating DNA as
      a biomarker.

PMID- 19747473
TI  - Long-term stability of procalcitonin in frozen samples and comparison of Kryptor
      and VIDAS automated immunoassays.
AB  - OBJECTIVES: To assess long-term stability of PCT in deep-frozen samples and
      assess whether Kryptor procalcitonin cutoff ranges can be transferred on the
      bioMerieux VIDAS system. DESIGN AND METHODS: Samples from two intervention
      studies (ProRESP and ProCAP) were retested on both systems and compared with
      Passing-Bablok regression, Bland-Altman difference plot, and analysis of
      concordance over 4 medically relevant cutoff ranges. RESULTS: Prolonged storage
      resulted in a significant decline of median procalcitonin values of 11.4% and
      13.5% in ProRESP and ProCAP cohorts. Regression analysis showed that both methods
      correlated well (r=0.982, n=304) but with a deviation from the line of identity
      (y=1.234x-0.018). The Bland-Altman plot indicated an average relative bias of
      17.1% (2 SD limits: -56.4% to 90.5%). Concordance over all 4 categories was
      82.6%, without a significant difference in frequency distribution between
      methods. CONCLUSION: An only modest decline of measured PCT levels of around 10%
      after long-term deep-frozen storage was found. The VIDAS procalcitonin assay
      showed good correlation and concordance with the established Kryptor method. Both
      techniques can be used with the same nominal procalcitonin cutoff ranges in
      clinical routine.

PMID- 19747474
TI  - Measurement of glucose and fructose in clinical samples using gas
      chromatography/mass spectrometry.
AB  - OBJECTIVE: The impact of increased fructose consumption on carbohydrate
      metabolism is a topic of current interest, but determination of serum level has
      been hindered due to low concentration and interference from serum glucose. We
      are reporting a method for the quantification of glucose and fructose in clinical
      samples using gas chromatography/mass spectrometry (GC/MS). The accuracy and
      precision of GC/MS and an enzymatic assay were compared. DESIGN AND METHODS: Mass
      spectrometry fragmentation patterns of methyloxime peracetate derivatized aldose
      and ketose were determined. Unique fragments for glucose and fructose were used
      for quantitative analysis using isotope labeled recovery standards. RESULTS:
      Methyloxime peracetate derivatives of glucose and fructose showed characteristic
      loss of acetate (M-60) or ketene (M-42) under chemical ionization (CI). Under
      electron impact (EI) ionization, a unique C1-C2 fragment of glucose was formed,
      while a C1-C3 fragment was formed from keto-hexoses. These unique fragments were
      used in the quantitative assay of glucose and fructose in clinical samples. In
      clinical samples, the GC/MS assay has a lower limit of detection than that of the
      enzymatic assay. In plasma samples from patients evaluated for diabetes the
      average serum glucose and fructose were 6.19+/-2.72 mM and 46+/- 25.22 microM.
      Fructose concentrations in many of these samples were below the limit of
      detection of the enzymatic method. CONCLUSION: Derivatization of aldose and
      ketose monosaccharides to their respective O-methyloxime acetates for GC/MS
      analysis is a facile method for determination of serum/plasma glucose and
      fructose samples.

PMID- 19747475
TI  - Cryopreservation of marine thraustochytrids (Labyrinthulomycetes).
AB  - In this research, the viability of three marine thraustochytrid isolates (fungoid
      protists) (WSG05, W15 and WH3) were investigated after freezing in liquid
      nitrogen. Five cryopreservative combinations containing horse serum, glycerol and
      dimethylsulfide (Me(2)SO) were used. The thraustochytrids were assessed directly
      after removal from liquid nitrogen and cell concentration measured for 10 days
      post-thawing. Results indicated that a combination of horse serum and Me(2)SO
      were the most effective cryoprotectants for each of the strains tested. Glycerol
      was only successful in producing growth in one of the strains once thawed. The
      protocols developed and tested in this study may have further application for
      cryopreserving other isolates in this class.

PMID- 19747476
TI  - Grandparental stem cells in leech segmentation: differences in CDC42 expression
      are correlated with an alternating pattern of blast cell fates.
AB  - Embryonic segmentation in clitellate annelids (oligochaetes and leeches) is a
      cell lineage-driven process. Embryos of these worms generate a posterior growth
      zone consisting of 5 bilateral pairs of identified segmentation stem cells
      (teloblasts), each of which produces a column of segmental founder cells (blast
      cells). Each blast cell generates a lineage-specific clone via a stereotyped
      sequence of cell divisions, which are typically unequal both in terms of the
      relative size of the sister cells and in the progeny to which they give rise. In
      two of the five teloblast lineages, including the ventralmost, primary neurogenic
      (N) lineage, the blast cells adopt two different fates, designated nf and ns, in
      exact alternation within the blast cell column; this is termed a grandparental
      stem cell lineage. To lay groundwork for investigating unequal divisions in the
      leech Helobdella, we have surveyed the Helobdella robusta genome for genes
      encoding orthologs of the Rho family GTPases, including the rho, rac and cdc42
      sub-families, which are known to be involved in multiple processes involving cell
      polarization in other systems. We find that, in contrast to most other known
      systems the Helobdella genome contains two cdc42 orthologs, one of which is
      expressed at higher levels in the ns blast cells than in nf blast cells. We also
      demonstrate that the asymmetric divisions of the primary nf and ns blast cells
      are regulated by the polarized distribution of the activated form of the Cdc42
      protein, rather than by the overall level of expression. Our results provide the
      first molecular insights into the mechanisms of the grandparental stem cell
      lineages, a novel, yet evolutionarily ancient stem cell division pattern. Our
      results also provide an example in which asymmetries in the distribution of Cdc42
      activity, rather than in the overall levels of Cdc42 protein, are important
      regulating unequal divisions in animal cells.

PMID- 19747477
TI  - Cardiovascular effects of intravenous administered 26RFa, a novel RFamide peptide
      ligand for GPR103, in anaesthetised rats.
AB  - 26RFa, a novel RFamide-related peptide, has been identified as the endogenous
      ligand for GPR103, and the biological functions of this neuropeptide have not
      been well investigated. In the present study, the cardiovascular effects of
      intravenous administration of rat/mouse 26RFa were tested in rats. Intravenous
      administered 26RFa (100-800 nmol/kg, i.v.) caused a biphasic change in blood
      pressure, and an increase in heart rate in urethane-anaesthetised rats. The
      pressor effects induced by 26RFa were significantly inhibited by pretreatment
      with the alpha- and beta-adrenoreceptor antagonists. In contrast, the
      tachycardiac responses to 26RFa were significantly attenuated by bilateral
      cervical vagotomy and beta-adrenoreceptor antagonist propranolol. These data
      imply that the peripheral cardiovascular regulation of 26RFa might be involved in
      vagal components and catecholaminergic pathway. Furthermore, in order to evaluate
      the importance of the regions of 26RFa molecule in its cardiovascular regulation,
      the two C-terminal fragments of rat/mouse 26RFa, 26RFa(8-26) and 26RFa(19-26),
      were synthesized and investigated to address their peripheral cardiovascular
      responses in rats. Surprisingly, intravenous injections of 26RFa(8-26) and
      26RFa(19-26) (50-300 nmol/kg, i.v.) produced dose-dependent increases in blood
      pressure and heart rate, which exerted different sensitivities to bilateral
      vagotomy and beta-adrenergic receptor antagonist. The results indicate that
      intravenous administrations of 26RFa and its fragments induced their
      cardiovascular effects via different pathways, which further suggest that the N
      terminal residues of 26RFa are required for its cardiovascular activities.

PMID- 19747478
TI  - Thrombospondin-1 (TSP-1) up-regulates tissue inhibitor of metalloproteinase-1
      (TIMP-1) production in human tumor cells: exploring the functional significance
      in tumor cell invasion.
AB  - Thrombospondin-1 (TSP-1), a matrix-bound adhesive glycoprotein, has been shown to
      modulate tumor progression. We previously demonstrated that TSP-1 up-regulates
      matrix metalloproteinases MMP-2 and MMP-9. Our studies suggested that the balance
      between MMPs and tissue inhibitors of metalloproteinases (TIMPs) is a key
      determinant in tumor cell invasion. We now report that TSP-1 up-regulates TIMP-1
      expression in both human breast and prostate cancer cell lines. The effect of TSP
      1 on TIMP-1 expression was examined in human breast adenocarcinoma cell lines
      (MDA-MB-231) and human prostate cancer cell lines (PC3-NI and PC3-ML) treated
      with exogenous TSP-1. TIMP-1 expression was also examined in TSP-1 stably
      transfected breast cancer cell line (MDA-MB-435). Northern and western blot
      analysis revealed TIMP-1 mRNA and TIMP-1 protein expression increased with
      increasing concentrations of TSP-1. This effect was inhibited by antibodies
      against the type I repeat domain of TSP-1 further suggesting that TSP-1 mediates
      TIMP-1 secretion. Inhibition of TSP-1 induced TIMP-1 levels increased tumor cell
      invasion. We conclude that TSP-1 is involved in influencing the critical balance
      between MMPs and their inhibitors, maintaining the controlled degradation of the
      extracellular matrix needed to support metastasis and our results may provide an
      explanation for the divergent activities reported for TSP-1 in tumor progression.

PMID- 19747479
TI  - Heparin cofactor II in atherosclerotic lesions from the Pathobiological
      Determinants of Atherosclerosis in Youth (PDAY) study.
AB  - Heparin cofactor II (HCII) is a serine protease inhibitor (serpin) that has been
      shown to be a predictor of decreased atherosclerosis in the elderly and
      protective against atherosclerosis in mice. HCII inhibits thrombin in vitro and
      HCII-thrombin complexes have been detected in human plasma. Moreover, the
      mechanism of protection against atherosclerosis in mice was determined to be the
      inhibition of thrombin. Despite this evidence, the presence of HCII in human
      atherosclerotic tissue has not been reported. In this study, using samples of
      coronary arteries obtained from the Pathobiological Determinants of
      Atherosclerosis in Youth (PDAY) study, we explore the local relationship between
      HCII and (pro)thrombin in atherosclerosis. We found that HCII and (pro)thrombin
      are co-localized in the lipid-rich necrotic core of atheromas. A significant
      positive correlation between each protein and the severity of the atherosclerotic
      lesion was present. These results suggest that HCII is in a position to inhibit
      thrombin in atherosclerotic lesions where thrombin can exert a proatherogenic
      inflammatory response. However, these results should be tempered by the
      additional findings from this, and other studies, that indicate the presence of
      other plasma proteins (antithrombin, albumin, and alpha(1)-protease inhibitor) in
      the same localized region of the atheroma.

PMID- 19747480
TI  - Muscle-conditioned media and cAMP promote survival and neurite outgrowth of adult
      spinal cord motor neurons.
AB  - Embryonic spinal cord motor neurons (MNs) can be maintained in vitro for weeks
      with a cocktail of trophic factors and muscle-derived factors under serum
      containing conditions. Here we investigated the beneficial effects of muscle
      derived factors in the form of muscle-conditioned medium (MCM) on the survival
      and neurite outgrowth of adult rat spinal cord MNs under serum-free conditions.
      Ventral horn dissociated cell cultures from the cervical enlargement were
      maintained in the presence of one or more of the following factors: brain-derived
      neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF), a cell
      permeant cyclic adenosine-3',5'-monophosphate (cAMP) analog and MCM. The cell
      cultures were immunostained with several antibodies recognizing a general
      neuronal marker the microtubule-associated protein 2 (MAP2) and either one or
      more motor neuronal markers: the non-phosphorylated neurofilament heavy isoform
      (SMI32), the transcription factors HB9 and Islet-1 and the choline acetyl
      transferase. We found that treatment with MCM together with the cAMP analog was
      sufficient to promote selective survival and neurite outgrowth of adult spinal
      cord MNs. These conditions can be used to maintain adult spinal cord MNs in
      dissociated cultures for several weeks and may have therapeutic potential
      following spinal cord injury or motor neuropathies. More studies are necessary to
      evaluate how MCM and the cAMP analog act in synergy to promote the survival and
      neurite outgrowth of adult MNs.

PMID- 19747482
TI  - Trypanosoma cruzi: Immunological predictors of benznidazole efficacy during
      experimental infection.
AB  - C3H/HeN male mice were infected with a lethal population of Trypanosoma cruzi and
      treated with benznidazole (Bz). Parasitemia, body weight and survival rate were
      registered during the therapy with significant improvement for T. cruzi-infected
      Bz-treated animals. Besides, flow cytometry resulted a useful method to
      discriminate between cured animals from those not cured by monitoring IgG(1)
      bound to live trypomastigotes levels. At the end of Bz therapy, the LT splenocyte
      compartment was studied for activation/memory cell surface markers (CD(69)(+) and
      CD(44)(+)). Cytofluorometric analysis showed that T. cruzi-infected untreated
      mice increased their activated LT numbers and this effect was completely
      abolished only in cured mice at the end of Bz administration. The same behavior
      was observed for the memory LT subpopulation correlating to an effector memory
      (CD(62L)(-)) displayed by T. cruzi infection. Bz treatment was able to modulate
      the immunological response by reducing the deleterious effect of the acute phase
      in all T. cruzi-infected mice.

PMID- 19747483
TI  - Lack of resistance against the tick Ixodes ricinus in two related passerine bird
      species.
AB  - Although many wild bird species may act as reservoir hosts for tick-transmitted
      diseases and/or support long-distance dispersal of infected ticks, to date no
      research has been done on the extent to which songbirds may acquire resistance to
      ixodid ticks. Here we investigate whether two passerine species belonging to the
      family Paridae, the blue tit (Cyanistes caeruleus) and the great tit (Parus
      major), are able to acquire resistance after repeated infestations with Ixodes
      ricinus nymphs. As blue tits are less frequently exposed to I. ricinus in the
      wild than great tits, we expected I. ricinus to be less adapted towards the blue
      tit's resistance mechanisms. Over the three infestation sessions we observed
      consistently high tick attachment rates and yields, high engorgement weights, and
      short engorgement and moulting durations, indicating that neither of the two
      songbird species is able to mount effective immune responses against I. ricinus
      nymphs after repeated infestations. As a consequence of the lack of resistance,
      birds were unable to prevent the direct harm (acute blood depletion) caused by
      tick feeding. Birds compensated the erythrocyte loss without reduction in general
      body condition (body mass corrected for tarsus length). The lack of resistance
      suggests that I. ricinus has a long co-evolutionary history with both avian
      hosts, which enables the tick to avoid or suppress the host's resistance
      responses.

PMID- 19747481
TI  - Signaling effect of amyloid-beta(42) on the processing of AbetaPP.
AB  - The effects of amyloid-beta are extremely complex. Current work in the field of
      Alzheimer disease is focusing on discerning the impact between the physiological
      signaling effects of soluble low molecular weight amyloid-beta species and the
      more global cellular damage that could derive from highly concentrated and/or
      aggregated amyloid. Being able to dissect the specific signaling events, to
      understand how soluble amyloid-beta induces its own production by up-regulating
      BACE1 expression, could lead to new tools to interrupt the distinctive feedback
      cycle with potential therapeutic consequences. Here we describe a positive loop
      that exists between the secretases that are responsible for the generation of the
      amyloid-beta component of Alzheimer disease. According to our hypothesis, in
      familial Alzheimer disease, the primary overproduction of amyloid-beta can induce
      BACE1 transcription and drive a further increase of amyloid-beta precursor
      protein processing and resultant amyloid-beta production. In sporadic Alzheimer
      disease, many factors, among them oxidative stress and inflammation, with
      consequent induction of presenilins and BACE1, would activate a loop and proceed
      with the generation of amyloid-beta and its signaling role onto BACE1
      transcription. This concept of a signaling effect by and feedback on the amyloid
      beta precursor protein will likely shed light on how amyloid-beta generation,
      oxidative stress, and secretase functions are intimately related in sporadic
      Alzheimer disease.

PMID- 19747484
TI  - Adult zebrafish heart as a model for human heart? An electrophysiological study.
AB  - The zebrafish has recently emerged as an excellent model for studies of heart
      development and regeneration. The physiology of the zebrafish heart has been
      suggested to resemble that of the human heart in many aspects, whereas, in
      contrast to mammals, the zebrafish has a remarkable ability to regenerate after
      heart injury. Thus, zebrafish have been proposed as a cost-effective model for
      genetic and pharmacological screens of factors affecting heart function and
      repair. However, realizing the full potential of the zebrafish heart as a model
      will require a better understanding of the electrophysiology of the adult
      zebrafish myocardium. Here, we characterize action potentials (APs) from intact
      adult atria and ventricles and find that the overall shape of zebrafish APs is
      similar to that of humans. We show that zebrafish, like most mammals, display
      functional acetylcholine-activated K(+) channels in the atrium, but not in the
      ventricle. Furthermore, the zebrafish AP upstroke is dominated by Na(+) channels,
      L-type Ca(2+) channels contribute to the plateau phase and I(Kr) channels are
      involved in repolarization. However, despite these similarities between zebrafish
      and mammalian electrophysiology, we also identified important differences. In
      particular, zebrafish display a robust T-type Ca(2+) current in both atrial and
      ventricular cardiomyocytes. Interestingly, in most mammals T-type Ca(2+) channels
      are only expressed in the developing heart or under pathophysiological
      conditions, indicating that adult zebrafish cardiomyocytes display a more
      immature phenotype.

PMID- 19747485
TI  - Regulated expression of the alpha isoform of the human thromboxane A2 receptor
      during megakaryocyte differentiation: a coordinated role for WT1, Egr1, and Sp1.
AB  - Thromboxane plays an essential role in hemostasis, regulating platelet
      aggregation and vessel tone. In humans, it signals through the TPalpha and TPbeta
      isoforms that are transcriptionally regulated by distinct promoters Prm1 and
      Prm3, respectively. Herein, the consequence of megakaryocytic differentiation on
      Prm1-directed TPalpha expression was investigated. Phorbol 12-myristate 13
      acetate (PMA) treatment substantially increased TPalpha mRNA and Prm1-directed
      gene expression in human erythroleukemia and K562 cells. Deletional analyses
      localized the major responsive element(s) to the upstream -8500 to -7504 region
      while mutation of four WT1/Egr1/Sp1 cis elements therein established that each
      contributes to the induction. Moreover, PMA increased Egr1, but not WT1 or Sp1,
      expression while the NGFI-A-binding protein 1 co-repressor impaired PMA induction
      of Egr1- and Prm1-directed gene expression. Chromatin immunoprecipitations
      established that WT1 is predominantly bound in vivo to the 5' Prm1 region in non
      differentiated human erythroleukemia cells. In response to PMA, there was initial
      induction in Egr1 and associated reduction in WT1 binding to Prm1 in vivo, which
      was displaced by Sp1 following sustained treatment. Collectively, data establish
      that regulated WT1 followed by sequential Egr1 and Sp1 binding to elements within
      Prm1 mediate repression and subsequent induction of TPalpha during
      differentiation into the megakaryocytic phenotype, shedding significant insights
      into factors regulating TPalpha expression therein.

PMID- 19747486
TI  - Modeling of the genetic switch of bacteriophage TP901-1: A heteromer of CI and
      MOR ensures robust bistability.
AB  - The lytic-lysogenic switch of the temperate lactococcal phage TP901-1 is
      fundamentally different from that of phage lambda. In phage TP901-1, the lytic
      promoter P(L) is repressed by CI, whereas repression of the lysogenic promoter
      P(R) requires the presence of both of the antagonistic regulator proteins, MOR
      and CI. We model the central part of the switch and compare the two cases for
      P(R) repression: the one where the two regulators interact only on the DNA and
      the other where the two regulators form a heteromer complex in the cytoplasm
      prior to DNA binding. The models are analyzed for bistability, and the predicted
      promoter repression folds are compared to experimental data. We conclude that the
      experimental data are best reproduced the latter case, where a heteromer complex
      forms in solution. We further find that CI sequestration by the formation of
      MOR:CI complexes in cytoplasm makes the genetic switch robust.

PMID- 19747487
TI  - Coupling of calcium and substrate binding through loop alignment in the outer
      membrane transporter BtuB.
AB  - In Gram-negative bacteria, TonB-dependent outer-membrane transporters bind large,
      scarce organometallic substrates with high affinity preceding active transport.
      The cobalamin transporter BtuB requires the additional binding of two Ca(2+) ions
      before substrate binding can occur, but the underlying molecular mechanism is
      unknown. Using the crystallographic structures available for different bound
      states of BtuB, we have carried out extended molecular dynamics simulations of
      multiple functional states of BtuB to address the role of Ca(2+) in substrate
      recruitment. We find that Ca(2+) binding both stabilizes and repositions key
      extracellular loops of BtuB, optimizing interactions with the substrate.
      Interestingly, replacement by Mg(2+) abolishes this effect, in accordance with
      experiments. Using a set of new force-field parameters developed for
      cyanocobalamin, we also simulated the substrate-bound form of BtuB, where we
      observed interactions not seen in the crystal structure between the substrate and
      loops previously found to be important for binding and transport. Based on our
      results, we suggest that the large size of cobalamin compared to other TonB
      dependent transporter substrates explains the requirement of Ca(2+) binding for
      high-affinity substrate recruitment in BtuB.

PMID- 19747488
TI  - Copper activation of NF-kappaB signaling in HepG2 cells.
AB  - Copper is a persistent environmental contaminant, and exposure to elevated levels
      of this transition metal can result in a variety of pathologies. Copper affects
      the transcription of multiple defense and repair genes to protect against metal
      induced pathologies. HepG2 cells were treated with copper under multiple
      conditions and microarray analyses were previously performed to better understand
      the mechanisms by which copper affects the transcription of stress-responsive
      genes. Analysis of the microarray data indicated that copper modulates multiple
      signal transduction pathways, including those mediated by NF-kappaB. Luciferase
      assays, quantitative reverse transcription real-time PCR, and chemical inhibition
      in HepG2 cells validated the microarray results and confirmed that NF-kappaB was
      activated by stress-inducible concentrations of copper. In addition, two novel NF
      kappaB-regulated genes, SRXN1 (sulfiredoxin 1 homolog) and ZFAND2A (zinc-finger,
      AN1-type domain 2A), were identified. Our results indicate that the activation of
      NF-kappaB may be important for survival under elevated concentrations of copper.

PMID- 19747489
TI  - Mutations that alter RcdA surface residues decouple protein localization and CtrA
      proteolysis in Caulobacter crescentus.
AB  - Periodic activation and deactivation of the essential transcriptional regulator
      CtrA is necessary to drive cell cycle progression in Caulobacter crescentus. At
      the onset of DNA replication (the G1-S cell cycle transition), CtrA and the AAA+
      protease ClpXP colocalize at one cell pole along with three accessory proteins,
      RcdA, CpdR, and PopA, and CtrA is rapidly degraded. RcdA is required for polar
      sequestration and regulated proteolysis of CtrA in vivo, but it does not
      stimulate CtrA degradation by ClpXP in vitro; thus, the function of RcdA is
      unknown. We determined the 2.9-A-resolution crystal structure of RcdA and
      generated structure-guided mutations in rcdA. We assayed the ability of each RcdA
      variant to support CtrA proteolysis and polar protein localization in
      Caulobacter. Deletion of an intrinsically disordered peptide at the C-terminus of
      RcdA prevents efficient CtrA degradation and blocks the transient localization of
      RcdA and CtrA at the cell pole. Surprisingly, substitutions in two groups of
      highly conserved, charged surface residues disrupt polar RcdA or CtrA
      localization but do not affect CtrA proteolysis. This is the first report showing
      that localization of RcdA can be decoupled from its effects on CtrA degradation.
      In addition, we used epistasis experiments to show that RcdA is still required
      for regulated CtrA proteolysis when all SsrA-tagged proteins, abundant substrates
      of ClpXP, are absent from the cell. Our results argue that RcdA stimulates CtrA
      proteolysis neither by localizing CtrA at the cell pole nor by preventing
      competition from SsrA-tagged substrates.

PMID- 19747490
TI  - Molecular insights into the interaction between alpha-synuclein and
      docosahexaenoic acid.
AB  - alpha-Synuclein (alpha-syn) is a 140-residue protein of unknown function,
      involved in several neurodegenerative disorders, such as Parkinson's disease.
      Recently, the possible interaction between alpha-syn and polyunsaturated fatty
      acids has attracted a strong interest. Indeed, lipids are able to trigger the
      multimerization of the protein in vitro and in cultured cells. Docosahexaenoic
      acid (DHA) is one of the main fatty acids (FAs) in cerebral gray matter and is
      dynamically released following phospholipid hydrolysis. Moreover, it has been
      found in high levels in brain areas containing alpha-syn inclusions in patients
      affected by Parkinson's disease. Debated and unsolved questions regard the nature
      of the molecular interaction between alpha-syn and DHA and the effect exerted by
      the protein on the aggregated state of the FA. Here, we show that alpha-syn is
      able to strongly interact with DHA and that a mutual effect on the structure of
      the protein and on the physical state of the lipid derives from this interaction.
      alpha-Syn acquires an alpha-helical conformation in a simple two-state
      transition. The binding of the protein to the FA leads to a reduction of the size
      of the spontaneously formed aggregated species of DHA as well as of the critical
      aggregate concentration of the lipid. Specifically, biophysical methods and
      electron microscopy observations indicated that the FA forms oil droplets in the
      presence of alpha-syn. Limited proteolysis experiments showed that, when the
      protein is bound to the FA oil droplets, it is initially cleaved in the 89-102
      region, suggesting that this chain segment is sufficiently flexible or unfolded
      to be protease-sensitive. Subsequent proteolytic events produce fragments
      corresponding to the first 70-80 residues that remain structured and show high
      affinity for the lipid. The fact that a region of the polypeptide chain remains
      accessible to proteases, when interacting with the lipid, suggests that this
      region could be involved in other interactions, justifying the ambivalent
      propensity of alpha-syn towards folding or aggregation in the presence of FAs.

PMID- 19747491
TI  - RelB and RelE of Escherichia coli form a tight complex that represses
      transcription via the ribbon-helix-helix motif in RelB.
AB  - RelB, the ribbon-helix-helix (RHH) repressor encoded by the relBE toxin-antitoxin
      locus of Escherichia coli, interacts with RelE and thereby counteracts the mRNA
      cleavage activity of RelE. In addition, RelB dimers repress the strong relBE
      promoter and this repression by RelB is enhanced by RelE; that is, RelE functions
      as a transcriptional co-repressor. RelB is a Lon protease substrate, and Lon is
      required both for activation of relBE transcription and for activation of the
      mRNA cleavage activity of RelE. Here we characterize the molecular interactions
      important for transcriptional control of the relBE model operon. Using an in vivo
      screen for relB mutants, we identified multiple nucleotide changes that map to
      important amino acid positions within the DNA-binding domain formed by the N
      terminal RHH motif of RelB. Analysis of DNA binding of a subset of these mutant
      RHH proteins by gel-shift assays, transcriptional fusion assays and a structure
      model of RelB-DNA revealed amino acid residues making crucial DNA-backbone
      contacts within the operator (relO) DNA. Mutational and footprinting analyses of
      relO showed that RelB dimers bind on the same face of the DNA helix and that the
      RHH motif recognizes four 6-bp repeats within the bipartite binding site. The
      spacing between each half-site was found to be essential for cooperative
      interactions between adjacently bound RelB dimers stabilized by the co-repressor
      RelE. Kinetic and stoichiometric measurements of the interaction between RelB and
      RelE confirmed that the proteins form a high-affinity complex with a 2:1
      stoichiometry. Lon degraded RelB in vitro and degradation was inhibited by RelE,
      consistent with the proposal that RelE protects RelB from proteolysis by Lon in
      vivo.

PMID- 19747492
TI  - Do immunotherapy and beta cell replacement play a synergistic role in the
      treatment of type 1 diabetes?
AB  - Type 1 diabetes (T1D) is the result of the autoimmune response against pancreatic
      insulin-producing ss-cells. Its ultimate consequence is beta-cell insufficiency
      mediated dysregulation of blood glucose control. In terms of T1D treatment,
      immunotherapy addresses the cause of T1D, mainly through re-setting the balance
      between autoimmunity and regulatory mechanisms. Regulatory T cells play an
      important role in this immune intervention. An alternative T1D treatment is beta
      cell replacement, which can reverse the consequence of the disease by replacing
      destroyed beta-cells in the diabetic pancreas. The applicable insulin-producing
      cells can be directly obtained from islet transplantation or generated from other
      cell sources such as autologous adult stem cells, embryonic stem cells, and
      induced pluripotent stem cells. In this review, we summarize the recent research
      progress and analyze the possible advantages and disadvantages of these two
      therapeutic options especially focusing on the potential synergistic effect on
      T1D treatment. Exploring the optimal combination of immunotherapy and beta-cell
      replacement will pave the way to the most effective cure for this devastating
      disease.

PMID- 19747493
TI  - A reliable Taylor series-based computational method for the calculation of
      dynamic sensitivities in large-scale metabolic reaction systems: algorithm and
      software evaluation.
AB  - Dynamic sensitivity analysis has become an important tool to successfully
      characterize all sorts of biological systems. However, when the analysis is
      carried out on large scale systems, it becomes imperative to employ a highly
      accurate computational method in order to obtain reliable values. Furthermore,
      the preliminary laborious mathematical operations required by current software
      before the computation of dynamic sensitivities makes it inconvenient for a
      significant number of unacquainted users. To satisfy these needs, the present
      work investigates a newly developed algorithm consisting of a combination of
      Taylor series method that can directly execute Taylor expansions for simultaneous
      non-linear-differential equations and a simple but highly-accurate numerical
      differentiation method based on finite-difference formulas. Applications to three
      examples of biochemical systems indicate that the proposed method makes it
      possible to compute the dynamic sensitivity values with highly-reliable
      accuracies and also allows to readily compute them by setting up only the
      differential equations for metabolite concentrations in the computer program.
      Also, it is found that the Pade approximation introduced in the Taylor series
      method shortens the computation time greatly because it stabilizes the
      computation so that it allows us to use larger stepsizes in the numerical
      integration. Consequently, the calculated results suggest that the proposed
      computational method, in addition to being user-friendly, makes it possible to
      perform dynamic sensitivity analysis in large-scale metabolic reaction systems
      both efficiently and reliably.

PMID- 19747494
TI  - Swim stress enhances nociceptin/orphanin FQ-induced inhibition of rat dorsal
      raphe nucleus activity in vivo and in vitro: role of corticotropin releasing
      factor.
AB  - The effects of nociceptin/orphanin FQ on putative serotonin (5HT) neurons of the
      dorsal raphe nucleus (DRN), known to modulate the behavioral responses to stress,
      were investigated in vivo and in vitro. In DRN slices from unstressed rats,
      nociceptin/orphanin FQ concentration-dependently inhibited the firing rate of
      putative 5HT neurons (EC(50) = 21.6 +/- 1.21 nM) and the selective NOP receptor
      antagonist UFP-101 shifted the concentration-response curve to the right
      (estimated pA(2) 6.86). Nociceptin/orphanin FQ potency was enhanced in slices
      prepared from rats previously subjected to a 15 min swim stress (EC(50) = 1.98 +/
      0.11 nM). Swim stress did not change the number or affinity of NOP receptors in
      DRN. Stress-elicited potentiation involved corticotropin-releasing factor
      (CRF)(1) receptors, GABA signaling and protein synthesis, being attenuated by pre
      treatment with antalarmin (20 mg/kg, i.p.), diazepam (2.4 mg/kg, i.p.) and
      cycloheximide (2.5 mg/kg, i.p.), respectively. In anesthetized unstressed rats,
      locally applied nociceptin/orphanin FQ (0.03 and 0.1 ng/30 nl) inhibited the
      firing rate of DRN neurons (to 80 +/- 7 and 54 +/- 10% of baseline,
      respectively). Nociceptin/orphanin FQ inhibition was potentiated both 24 h after
      swim stress and 1 h after CRF (30 ng/30 nl intra-DRN). Stress-induced
      potentiation was prevented by the selective CRF(1) receptor antagonist, NBI 30755
      (20 mg/kg, i.p.). In contrast, the inhibitory response of DRN neurons to the
      5HT(1A) agonist, 8OH-DPAT (1 microg/1 microl, intra-DRN) was not potentiated by
      swim stress, ruling out a non-specific enhanced permeability of GIRK channel.
      Together, these findings suggest that CRF and the nociceptin/orphanin FQ/NOP
      system interact in the DRN during stress to control 5HT transmission; this may
      play a role in stress-related neuropsychopathologies.

PMID- 19747495
TI  - Reduced expression of glutamate transporters vGluT1, EAAT2 and EAAT4 in learned
      helpless rats, an animal model of depression.
AB  - BACKGROUND: It has been widely accepted that glial pathology and disturbed
      synaptic transmission contribute to the neurobiology of depression. Apart from
      monoaminergic alterations, an influence of glutamatergic signal transduction has
      been reported. Therefore, gene expression of glutamate transporters that strictly
      control synaptic glutamate concentrations have to be assessed in animal models of
      stress and depression. METHODS: We performed in situ-hybridizations in learned
      helplessness rats, a well established animal model of depression, to assess
      vGluT1 and EAAT1-4. Sprague-Dawley rats of two inbred lines were tested for
      helpless behavior and grouped into three cohorts according to the number of
      failures to stop foot shock currents by lever pressing. RESULTS: Helpless animals
      showed a significantly suppressed expression of the glial glutamate transporter
      EAAT2 (rodent nomenclature GLT1) in hippocampus and cerebral cortex compared to
      littermates with low failure rate and not helpless animals. This finding was
      validated on protein level using immunohistochemistry. Additionally, expression
      levels of EAAT4 and the vesicular transporter vGluT1 were reduced in helpless
      animals. In contrast, the transcript levels of EAAT1 (GLAST) and EAAT3 (EAAC1)
      were not significantly altered. CONCLUSIONS: These results strongly suggest
      reduced astroglial glutamate uptake and implicate increased glutamate levels in
      learned helplessness. The findings are in concert with antidepressant effects of
      NMDA-receptor antagonists and the hypotheses that impaired astroglial functions
      contribute to the pathogenesis of affective disorders.

PMID- 19747496
TI  - Differential anti-neuropathic pain effects of tetrodotoxin in sciatic nerve-
      versus infraorbital nerve-ligated rats--behavioral, pharmacological and
      immunohistochemical investigations.
AB  - Several voltage-gated sodium channels are expressed in primary sensory neurons
      where they control excitability and participate in the generation and propagation
      of action potentials. Peripheral nerve injury-induced alterations in both
      tetrodotoxin (TTX)-sensitive and TTX-resistant sodium channels have been proposed
      to contribute to neuropathic pain caused by such lesion. We herein investigated
      whether the blockade of TTX-sensitive channels could reduce pain-related
      behaviors and evoked c-Fos immunoreactivity in rats with neuropathic pain
      produced by chronic unilateral constriction injury to either the sciatic nerve or
      the infraorbital nerve. Acute as well as subchronic administration of TTX (1-6
      mug/kg s.c.) was found to suppress for up to 3 h allodynia and hyperalgesia in
      sciatic nerve-ligated rats. In contrast, TTX was only moderately effective in
      rats with ligated infraorbital nerve. In sciatic nerve-ligated rats, TTX
      administration prevented the increased c-Fos immunoreactivity occurring in the
      dorsal horn of the lumbar cord and some supraspinal areas in response to light
      mechanical stimulation of the nerve-injured hindpaw. The anti
      allodynia/antihyperalgesia caused by TTX in these neuropathic rats was promoted
      by combined treatment with naloxone (0.5 mg/kg s.c.) but unaffected by the 5
      HT(1B) receptor antagonist F11648 (0.5 mg/kg s.c.) and the alpha(2)-adrenergic
      receptor antagonist idazoxan (0.5 mg/kg i.v.). In contrast, the anti-allodynic
      and anti-hyperalgesic effects of TTX were significantly attenuated by co
      administration of morphine (3 mg/kg s.c.) or the cholecystokinin(2)-receptor
      antagonist CI-1015 (0.1 mg/kg i.p.). These results indicate that TTX alleviates
      pain-related behaviors in sciatic nerve-lesioned rats through mechanisms that
      involve complex interactions with opioidergic systems.

PMID- 19747497
TI  - Automaticity and attention in Huntington's disease: when two hands are not better
      than one.
AB  - People with Huntington's disease (HD) commonly report difficulty carrying out two
      everyday tasks simultaneously. This difficulty, confirmed by experimental
      studies, is typically ascribed to impaired attention. Yet, dual-task problems
      extend to relatively simple tasks, such as walking and talking, which would
      ordinarily be considered relatively undemanding of attention. The study tests the
      hypothesis that in HD there is a deficit in the ability to automatise task
      performance. Thus, simple tasks, which place minimal demands on conscious
      attention in healthy controls, make disproportionately high demands on
      attentional resources in HD. We examined the performance of HD patients and
      healthy controls on a simple, paced finger-tapping task, comparing single-task
      (tapping with one hand) and dual-task (tapping with both hands simultaneously)
      performance. For HD patients, bimanual tapping increased the task demands: there
      was greater variability in tapping rate and patients reported that the 'dual
      task' condition was more difficult. The opposite pattern was observed for
      controls. Variability in tapping performance in HD was highly correlated with
      performance on cognitive tasks that have the potential to be automatized but not
      with performance on tasks that are more demanding of executive control,
      suggesting a common substrate for cognitive and motor automaticity. The data
      support the hypothesis that HD patients are impaired in their capacity for
      automisation, and suggest that impaired automaticity may be one source of
      attentional deficits in HD. The findings have implications for the interpretation
      of 'high level' deficits in attention and executive function previously reported
      in HD.

PMID- 19747498
TI  - Size-dependent effects of tungsten carbide-cobalt particles on oxygen radical
      production and activation of cell signaling pathways in murine epidermal cells.
AB  - Hard metal or cemented carbide consists of a mixture of tungsten carbide (WC)
      (85%) and metallic cobalt (Co) (5-15%). WC-Co is considered to be potentially
      carcinogenic to humans. However, no comparison of the adverse effects of nano
      sized WC-Co particles is available to date. In the present study, we compared the
      ability of nano- and fine-sized WC-Co particles to form free radicals and
      propensity to activate the transcription factors, AP-1 and NF-kappaB, along with
      stimulation of mitogen-activated protein kinase (MAPK) signaling pathways in a
      mouse epidermal cell line (JB6 P(+)). Our results demonstrated that nano-WC-Co
      generated a higher level of hydroxyl radicals, induced greater oxidative stress,
      as evidenced by a decrease of GSH levels, and caused faster JB6 P(+) cell
      growth/proliferation than observed after exposure of cells to fine WC-Co. In
      addition, nano-WC-Co activated AP-1 and NF-kappaB more efficiently in JB6(+/+)
      cells as compared to fine WC-Co. Experiments using AP-1-luciferase reporter
      transgenic mice confirmed the activation of AP-1 by nano-WC-Co. Nano- and fine
      sized WC-Co particles also stimulated MAPKs, including ERKs, p38, and JNKs with
      significantly higher potency of nano-WC-Co. Finally, co-incubation of the
      JB6(+/+) cells with N-acetyl-cysteine decreased AP-1 activation and
      phosphorylation of ERKs, p38 kinase, and JNKs, thus suggesting that oxidative
      stress is involved in WC-Co-induced toxicity and AP-1 activation.

PMID- 19747499
TI  - Uranyl nitrate inhibits lactate gluconeogenesis in isolated human and mouse renal
      proximal tubules: a 13C-NMR study.
AB  - As part of a study on uranium nephrotoxicity, we investigated the effect of
      uranyl nitrate in isolated human and mouse kidney cortex tubules metabolizing the
      physiological substrate lactate. In the millimolar range, uranyl nitrate reduced
      lactate removal and gluconeogenesis and the cellular ATP level in a dose
      dependent fashion. After incubation in phosphate-free Krebs-Henseleit medium with
      5 mM L-[1-13C]-, or L-[2-13C]-, or L-[3-13C]lactate, substrate utilization and
      product formation were measured by enzymatic and NMR spectroscopic methods. In
      the presence of 3 mM uranyl nitrate, glucose production and the intracellular ATP
      content were significantly reduced in both human and mouse tubules. Combination
      of enzymatic and NMR measurements with a mathematical model of lactate metabolism
      revealed an inhibition of fluxes through lactate dehydrogenase and the
      gluconeogenic enzymes in the presence of 3 mM uranyl nitrate; in human and mouse
      tubules, fluxes were lowered by 20% and 14% (lactate dehydrogenase), 27% and 32%
      (pyruvate carboxylase), 35% and 36% (phosphoenolpyruvate carboxykinase), and 39%
      and 45% (glucose-6-phosphatase), respectively. These results indicate that
      natural uranium is an inhibitor of renal lactate gluconeogenesis in both humans
      and mice.

PMID- 19747500
TI  - High-fat diet exacerbates inflammation and cell survival signals in the skin of
      ultraviolet B-irradiated C57BL/6 mice.
AB  - Inflammation induced by chronic exposure to ultraviolet (UV) radiation has been
      implicated in various skin diseases. We formulated the hypothesis that a high-fat
      diet may influence the UV-induced inflammatory responses in the skin. C57BL/6
      mice were fed a high-fat diet or control diet and exposed to UVB radiation (120
      mJ/cm(2)) three times/week for 10 weeks. The mice were then sacrificed and skin
      and plasma samples collected for analysis of biomarkers of inflammatory responses
      using immunohistochemistry, western blotting, ELISA and real-time PCR. We found
      that the levels of inflammatory biomarkers were increased in the UVB-exposed skin
      of the mice fed the high-fat diet than the UVB-exposed skin of the mice fed the
      control diet. The levels of inflammatory biomarkers of early responses to UVB
      exposure (e.g., myeloperoxidase, cyclooxygenase-2, prostaglandin-E(2)),
      proinflammatory cytokines (i.e., tumor necrosis factor-alpha, interleukin-1beta,
      interleukin-6), and proliferating cell nuclear antigen and cell survival signals
      (phosphatidylinositol-3-kinase and p-Akt-Ser(473)) were higher in high-fat-diet
      fed mouse skin than control-diet-fed mouse skin. The plasma levels of insulin
      growth factor-1 were greater in the UVB-irradiated mice fed the high-fat diet
      than the UVB-irradiated mice fed the control diet, whereas the levels of plasma
      adiponectin were significantly lower. This pronounced exacerbation of the UVB
      induced inflammatory responses in the skin of mice fed a high-fat diet suggests
      that high-fat diet may increase susceptibility to inflammation-associated skin
      diseases, including the risk of skin cancer.

PMID- 19747501
TI  - Liver fibrosis in mice induced by carbon tetrachloride and its reversion by
      luteolin.
AB  - Hepatic fibrosis is effusive wound healing process in which excessive connective
      tissue builds up in the liver. Because specific treatments to stop progressive
      fibrosis of the liver are not available, we have investigated the effects of
      luteolin on carbon tetrachloride (CCl(4))-induced hepatic fibrosis. Male Balb/C
      mice were treated with CCl(4) (0.4 ml/kg) intraperitoneally (i.p.), twice a week
      for 6 weeks. Luteolin was administered i.p. once daily for next 2 weeks, in doses
      of 10, 25, and 50 mg/kg of body weight. The CCl(4) control group has been
      observed for spontaneous reversion of fibrosis. CCl(4)-intoxication increased
      serum aminotransferase and alkaline phosphatase levels and disturbed hepatic
      antioxidative status. Most of these parameters were spontaneously normalized in
      the CCl(4) control group, although the progression of liver fibrosis was observed
      histologically. Luteolin treatment has increased hepatic matrix metalloproteinase
      9 levels and metallothionein (MT) I/II expression, eliminated fibrinous deposits
      and restored architecture of the liver in a dose-dependent manner. Concomitantly,
      the expression of glial fibrillary acidic protein and alpha-smooth muscle actin
      indicated deactivation of hepatic stellate cells. Our results suggest the
      therapeutic effects of luteolin on CCl(4)-induced liver fibrosis by promoting
      extracellular matrix degradation in the fibrotic liver tissue and the strong
      enhancement of hepatic regenerative capability, with MTs as a critical mediator
      of liver regeneration.

PMID- 19747502
TI  - Colorectal cancer screening mode preferences among US veterans.
AB  - OBJECTIVE: To assess colorectal cancer (CRC) screening mode preferences and
      correlates of these preferences among US veterans at average risk for CRC.
      METHOD: A cross-sectional survey of a nationally representative sample of VA
      patients was conducted between January 2005 and December 2006. We report
      preference distributions for screening modes among 2068 average-risk veterans and
      across patient subgroups based on personal, behavioral, and environmental
      factors. Independent predictors of preferences are identified through
      hierarchical logistic regression models. RESULTS: Colonoscopy (37%) was the most
      preferred mode followed by fecal occult blood test (FOBT) (29%). The strongest
      predictors of preferences were previous screening experience, provider
      recommendation, and use of non-VA healthcare services. Participants in higher
      socioeconomic groups were more likely to choose colonoscopy and less likely to
      indicate no preference. CONCLUSION: Screening programs that offer only one mode
      fail to accommodate the preferences of a substantial proportion of patients.
      Within the VA, adding screening colonoscopy to programs currently offering only
      FOBT is likely to increase preferences for colonoscopy, as patients incorporate
      provider recommendations for and personal experience with colonoscopy into their
      preferences. This is likely to disproportionately benefit lower socioeconomic
      groups who do not currently have access to non-VA colonoscopy services.

PMID- 19747503
TI  - Analyzing the catalytic mechanism of protein tyrosine phosphatase PtpB from
      Staphylococcus aureus through site-directed mutagenesis.
AB  - Protein tyrosine phosphatase B (PtpB) from Staphylococcus aureus, MRSA 252, is a
      low molecular weight protein tyrosine phosphatase involved in its pathogenicity.
      PtpB has been modeled in silico and site-directed mutagenesis performed to
      ascertain the importance of active site residues Cys8, Arg14, Ser15 and Asp120 in
      its catalytic mechanism. Kinetic characterization of wild-type and the mutant
      PtpBs, C8S, R14A, S15T, S15A, D120A, D120E, D120N revealed the reaction mechanism
      followed by this LMWPTPase. The mutations caused major changes in the local
      environment resulting in significant decrease of its catalytic activity.
      Inhibition kinetics for the wild-type enzyme was performed with maleimide and
      maleimidobutyric acid.

PMID- 19747504
TI  - WITHDRAWN: Notification and Documentation of Blood Culture Results in
      Microbiology and Patient Records.
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- 19747505
TI  - Skin infection in children colonized with community-associated methicillin
      resistant Staphylococcus aureus.
AB  - OBJECTIVES: The relationship between community-associated methicillin-resistant
      Staphylococcus aureus (CA-MRSA) nasal colonization and subsequent infection in
      children is unknown. We sought to define risk factors for skin and soft tissue
      infection (SSTI) in community children. METHODS: A prior study measured S. aureus
      nasal colonization prevalence for 1300 community children. To detect subsequent
      SSTI in these children or a household member, surveys were administered 6 and 12
      months following enrollment. RESULTS: SSTIs were reported by 56/708 (8.1%)
      respondents during the initial 6-month interval. SSTI developed in 6/26 (23%)
      initially colonized with MRSA, 16/194 (8%) with methicillin-sensitive S. aureus
      colonization, and 34/474 (7%) not colonized with S. aureus (MRSA vs. not MRSA,
      univariate analysis, p = 0.014). In multivariable analysis, factors associated
      with SSTI included history of SSTI in the child during the year preceding
      enrollment (p < 0.01) and SSTI in household contacts during the follow-up
      interval (p<0.01); MRSA nasal colonization approached statistical significance (p
      = 0.08). CONCLUSIONS: In the current era of community MRSA transmission, SSTI is
      a disease of households, with recurrences in index cases and occurrences among
      household contacts. Children with MRSA colonization may be at risk for subsequent
      SSTI. Further study of MRSA transmission dynamics in households and preventive
      strategies should receive high priority.

PMID- 19747506
TI  - Fatal co-infection with swine origin influenza virus A/H1N1 and community
      acquired methicillin-resistant Staphylococcus aureus.
AB  - Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) co
      infection has been described previously in association with respiratory tract
      infection caused by seasonal influenza A viruses, but not with swine origin
      influenza A (H1N1) virus (S-OIV). We report the clinical and pathological
      findings of the first death with fulminant co-infection by CA-MRSA. Since early
      empirical treatment with beta-lactam plus fluoroquinolone or macrolides is often
      initiated before specimen collections, bacterial co-infection in S-OIV may have
      been under-reported.

PMID- 19747507
TI  - Time-frequency analysis methods to quantify the time-varying microstructure of
      sleep EEG spindles: possibility for dementia biomarkers?
AB  - The time-varying microstructure of sleep EEG spindles may have clinical
      significance in dementia studies and can be quantified with a number of
      techniques. In this paper, real and simulated sleep spindles were regarded as
      AM/FM signals modeled by six parameters that define the instantaneous envelope
      (IE) and instantaneous frequency (IF) waveforms for a sleep spindle. These
      parameters were estimated using four different methods, namely the Hilbert
      transform (HT), complex demodulation (CD), matching pursuit (MP) and wavelet
      transform (WT). The average error in estimating these parameters was lowest for
      HT, higher but still less than 10% for CD and MP, and highest (greater than 10%)
      for WT. The signal distortion induced by the use of a given method was greatest
      in the case of HT and MP. These two techniques would necessitate the removal of
      about 0.4s from the spindle data, which is an important limitation for the case
      of spindles with duration less than 1s. Although the CD method may lead to a
      higher error than HT and MP, it requires a removal of only about 0.23s of data.
      An application of this sleep spindle parameterization via the CD method is
      proposed, in search of efficient EEG-based biomarkers in dementia. Preliminary
      results indicate that the proposed parameterization may be promising, since it
      can quantify specific differences in IE and IF characteristics between sleep
      spindles from dementia subjects and those from aged controls.

PMID- 19747508
TI  - Effects of extinction on classical conditioning and conditioning-specific reflex
      modification of rabbit heart rate.
AB  - Understanding the mechanisms of fear extinction has become increasingly important
      for treating a number of disorders, particularly post-traumatic stress disorder.
      Conditioning of rabbit heart rate (HR) is an established model for studying fear,
      yet little is known about procedures for extinguishing it other than repeated
      presentations of cue(s) associated with the fear-inducing event. The following
      study examined the effects of conditioned stimulus (CS) alone, unconditioned
      stimulus (US) alone, unpaired CS/US presentations, continued CS-US pairings, or
      no further stimulation on rabbit HR following HR conditioning. We have previously
      shown the rabbit HR response to the US can change as a function of learning when
      measured in the absence of the CS, a phenomenon referred to as conditioning
      specific reflex modification (CRM). More specifically, the HR exhibits a
      deceleration in response to the US reminiscent of the conditioned bradycardia
      that develops to the CS. Consequently, the following study also examined the
      effects of extinction treatments on HR CRM. For HR conditioned responses (CRs),
      CS-alone and unpaired CS/US presentations were the most successful extinction
      treatments. For HR CRM, all conditions led to a reduction in CRM except for a
      subset of rabbits that maintained high levels following unpaired extinction,
      indicating a dissociation between extinction of HR CRs and CRM. The findings
      highlight the parameters of HR extinction, the transient nature of HR CRM, vagal
      involvement in both acquisition and extinction of HR CRM, and suggest that HR CRM
      cannot be fully explained as a CR that has generalized from the CS to the US.

PMID- 19747509
TI  - D1 receptors involved in the acquisition of sexual experience in male rats.
AB  - As we found previously, changes in ultrasonic vocalizations in the 50-kHz band
      emitted before a female is introduced into a copulatory chamber (precontact
      vocalizations-PVs) and shortening of ejaculation latency (EL) in subsequent
      copulatory sessions are correlated and reflected acquisition of sexual experience
      in male rats. In the present experiments, we investigate the role of the D1
      receptor in this phenomenon. First, the effects of a D1 antagonist and D1
      agonists injected subcutaneously during the first sexual contacts were analyzed.
      The antagonist (SCH-23390) inhibited changes in PVs and EL as well as rearing (R)
      and mount latency (ML). Both agonists (SKF-38393 and selective SKF-82957)
      inhibited PVs also at doses where no effects on EL and ML were observed. Repeated
      injections of five agonists, with or without socio-sexual contacts, had an effect
      on later PVs and R (long-term effect) but not on copulatory performance during
      the subsequent four sessions. In the last experiment, a D1 agonist (SKF-82957,
      0.5 microg) was injected bilaterally into nucleus accumbens (N.Acc) before each
      of the first five sessions. The D1 agonist in N.Acc facilitated initiation of
      copulation in treatment-naive rats. Repeated administration of the D1 agonist
      into the brain had long-lasting effects on PVs, R and ML, probably as a result of
      long-term changes in neuronal structures involved in acquisition of sexual
      experience, in this part of the nucleus accumbens. Repeated D1 agonist
      administration probably inhibits/reverses sensitization processes in dopamine
      structures. The results indicate a role of D1 receptors in acquisition of socio
      sexual experience and suggest independent neuronal pathways for changes in PVs
      and EL.

PMID- 19747510
TI  - Aggression--interactions of serotonin and testosterone in healthy men and women.
AB  - Serotonin (5-HT) and testosterone (T) have both been implicated in the regulation
      of aggression. Findings in humans however are very inconclusive, with respect to
      main effects of either system. Animal models implicate T to modulate 5-HT system
      activity, and furthermore have shown behaviorally relevant interactions of T and
      5-HT with respect to aggression. We tested for associations between habitual T
      level and 5-HT system activity, as well as behaviorally relevant interactions of
      T and 5-HT with respect to trait aggression in 48 healthy male and female
      subjects. 5-HT activity was measured by means of neuroendocrine challenge
      paradigm with S-citalopram. T-levels were measured in saliva samples. Trait
      aggression was assessed by self-report measures. T-levels were not associated
      with indices of central 5-HT activity. Results showed significant interaction
      effects between 5-HT and T for trait aggression in men only (p<0.05). Trait
      aggression was significantly higher in the combinations "high T+high cortisol
      responses" (indicating decreased 5-HT availability), and "low T+low cortisol
      responses" (indicating increased 5-HT availability), after S-citalopram. Results
      support the notion of behaviorally relevant interactions between T and 5-HT, with
      respect to aggression in humans, but also indicate the need for further studies.

PMID- 19747511
TI  - Altered neuronal activities in the motor cortex with impaired motor performance
      in adult rats observed after infusion of cerebrospinal fluid from amyotrophic
      lateral sclerosis patients.
AB  - Although definite evidences are available to state that, neuronal activity is a
      prime determinant of animal behavior, the specific relationship between local
      field potentials of the motor cortex after intervention with CSF from human
      patients and animal behavior have remained opaque. The present study has
      investigated whether cerebrospinal fluid from sporadic amyotrophic lateral
      sclerosis (sALS) patients could disrupt neuronal activity of the motor cortex,
      which could be associated with disturbances in the motor performance of adult
      rats. CSF from ALS patients (ALS-CSF) was infused into the lateral ventricle of
      Wistar rats. After 24h, the impact of ALS-CSF on the local field potentials
      (LFPs) of the motor cortex and on the motor behavior of animals were examined.
      The results indicate that ALS-CSF produced a bivariate distribution on the
      relative power values of the LFPs of the motor cortex 24h following infusion.
      However, the behavioral results did not show bimodality, instead showed
      consistent decrease in motor performance: on rotarod and grip strength meter. The
      neuronal activity of the motor cortex negatively correlated with the duration of
      ALS symptoms at the time of lumbar puncture. Although the effect of ALS-CSF was
      more pronounced at 24h following infusion, the changes observed in LFPs and motor
      performance appeared to revert to baseline values at later time points of
      testing. In the current study, we have shown that, ALS-CSF has the potential to
      perturb neuronal activity of the rat motor cortex which was associated with poor
      performance on motor function tests.

PMID- 19747512
TI  - Modulation of JC virus transcription by C/EBPbeta.
AB  - The polyomavirus JC (JCV) causes the demyelinating disease progressive multifocal
      leukoencephalopathy (PML). Infection by JCV is very common in childhood after
      which the virus enters a latent state, which is poorly understood. Under
      conditions of severe immunosuppression, especially AIDS, JCV may reactivate to
      cause PML. Expression of JC viral proteins is regulated by the JCV non-coding
      control region (NCCR), which contains an NF-kappaB binding site previously shown
      to activate transcription. We now report that C/EBPbeta inhibits basal and NF
      kappaB-stimulated JCV transcription via the same site. Gel shift analysis showed
      C/EBPbeta bound to this region in vitro and ChIP assays confirmed this binding in
      vivo. Further, a ternary complex of NF-kappaB/p65, C/EBPbeta-LIP and JCV DNA
      could be detected in co-immunoprecipitation experiments. Mutagenesis analysis of
      the JCV NCCR indicated p65 and C/EBPbeta-LIP bound to adjacent but distinct sites
      and that both sites regulate basal and p65-stimulated transcription. Thus
      C/EBPbeta negatively regulates JCV, which together with NF-kappaB activation, may
      control the balance between JCV latency and activation leading to PML. This
      balance may be regulated by proinflammatory cytokines in the brain.

PMID- 19747513
TI  - Relationship between parental feeding styles and eating behaviours of Dutch
      children aged 6-7.
AB  - The present study assessed the relationship between parental feeding styles and
      dietary intake behaviours of Dutch children aged 6-7. Associations between
      feeding styles and dietary behaviours of the parents were also examined. We
      translated the validated 'Parental Feeding Style Questionnaire' and evaluated its
      factor structure. A cross-sectional survey was completed by one of the parents of
      135 children. Results indicated considerable similarity of factor structure,
      internal reliability and between-subscale correlations with the original
      instrument. The parental feeding dimensions of 'instrumental feeding' (i.e. using
      food as a reward) and 'emotional feeding' (i.e. feeding in response to children's
      emotional distress) were positively related to children's snacking behaviour. The
      feeding style 'encouragement to eat' was negatively associated with children's
      snacking behaviour. Various feeding styles were found to be related to parental
      dietary behaviours. Findings indicate the importance of acknowledging parental
      feeding styles in future research efforts as well as in the development of family
      based interventions promoting healthy eating habits among children.

PMID- 19747514
TI  - Leptin receptor mRNA in rat brain astrocytes.
AB  - We recently reported that mouse astrocytes express leptin receptors (ObR), and
      that obesity induces upregulation of astrocytic ObR. To provide further evidence
      of the importance of astrocytic ObR expression, we performed double-labeling
      fluorescent in situ hybridization (FISH) and immunohistochemistry in the rat
      hypothalamus. Laser confocal microscopic image analysis showed that ObR mRNA was
      present in glial fibrillary acidic protein (+) cells that show distinctive
      astrocytic morphology as well as in neurons. In addition to the presence of ObR
      mRNA, ObR protein was shown in both astrocytes and neurons in the rat
      hypothalamus by double-labeling immunohistochemistry. In cultured rat C6
      astrocytoma cells treated with different doses of lipopolysaccharide for 6h, the
      mRNA for ObRa or ObRb did not show significant changes, as measured by
      quantitative RT-PCR. However, the protein expression of both ObRa and ObRb,
      determined by Western blotting, was increased after the C6 cells were treated
      with either lipopolysaccharide or tumor necrosis factor-alpha. The results
      indicate that astrocytic ObR expression is present in rats as well as mice, and
      that it probably plays a role in the neuroinflammatory response.

PMID- 19747515
TI  - Proteomics approach for identifying osmotic-stress-related proteins in soybean
      roots.
AB  - Osmotic stress can endanger the survival of plants. To investigate the mechanisms
      by which plants respond to osmotic stress, protein profiles from soybean plants
      treated with polyethylene glycol (PEG) were monitored by a proteomics approach.
      Treatment with 10% aqueous PEG reduced the lengths of roots and hypocotyls of
      soybean seedlings. Proteins from soybean roots were separated by two-dimensional
      polyacrylamide gel electrophoresis, and 415 proteins were detected by Coomassie
      brilliant blue staining. Thirty-seven proteins changed by PEG treatment were
      analyzed using Edman sequencing and peptide-mass fingerprinting method and this
      group included proteins involved in disease/defense. Seven proteins were selected
      for further experiments using the results of cluster analysis and statistical
      analysis of the abundance change. A comparison with the effects of other abiotic
      stresses showed that caffeoyl-CoA-O-methyltransferase and 20S proteasome alpha
      subunit A were decreased and increased by abiotic stresses, respectively.
      Expression analyses of these transcripts were also changed by PEG treatment.
      Caffeoyl-CoA-O-methyltransferase and 20S proteasome alpha subunit A may control
      the sensitivity of several regulatory genes specific to short exposure to osmotic
      stress.

PMID- 19747516
TI  - 17beta-Estradiol modulates local cardiac renin-angiotensin system to prevent
      cardiac remodeling in the DOCA-salt model of hypertension in rats.
AB  - Ventricular remodeling can play a detrimental role in the progression of
      cardiovascular diseases, leading to heart failure. The current study was designed
      to investigate the effects of 17beta-estradiol (E2) on cardiac remodeling.
      Cardiac fibrosis and hypertrophy were examined in deoxycorticosterone acetate
      (DOCA)-salt treated rats with chronic, six-week administration of two different
      doses of E2. Bilaterally ovariectomized (Ovex) female Sprague-Dawley rats were
      randomly assigned to one of the following groups: Ovex-control; Ovex-DOCA; Ovex
      DOCA+low-dose E2 (1.66 microg/day); or Ovex-DOCA+high-dose E2 (2.38 microg/day).
      All DOCA-treated rats were uninephrectomized and drinking water was replaced by
      0.15M NaCl solution for the remainder of the study period. DOCA-salt treatment
      resulted in a significant increase in blood pressure, which was not altered by
      estrogen replacement. Histological examinations revealed marked cardiac
      remodeling (both ventricular hypertrophy and interstitial fibrosis) with DOCA
      treatment, which was attenuated in animals receiving estrogen therapy. Western
      blot analysis demonstrated increased cardiac levels of angiotensin converting
      enzyme (ACE) with DOCA treatment, which was attenuated by E2 replacement.
      Furthermore, increased levels of cardiac angiotensin converting enzyme 2 (ACE2)
      protein were observed in animals receiving high-dose E2 replacement. These
      findings suggest that physiologically relevant estrogen replacement therapy has
      blood pressure-independent cardioprotective effects, which are possibly mediated
      through modulation of the cardiac renin-angiotensin system.

PMID- 19747517
TI  - Molecular characterization of neuropeptide F from the eastern subterranean
      termite Reticulitermes flavipes (Kollar) (Isoptera: Rhinotermitidae).
AB  - Neuropeptide F (NPF)-like immunoreactivity was previously found to be abundant in
      the eastern subterranean termite, Reticulitermes flavipes. Purification of the
      NPF from a whole body extract of worker termites was accomplished in the current
      study by HPLC and heterologous radioimmunoassay for an NPF-related peptide,
      Helicoverpa zea Midgut Peptide-I. A partial amino acid sequence allowed
      determination of the corresponding cDNA that encoded an open reading frame
      deduced for authentic R. flavipes NPF (Ref NPF): KPSDPEQLADTLKYLEELDRFYSQVARPRFa.
      Effects of synthetic NPFs on muscle contractions were investigated for isolated
      foreguts and hindguts of workers, with Drm NPF inhibiting spontaneous
      contractions of hindguts. Phylogenetic analysis of invertebrate NPF sequences
      reveals two separate groupings, with Ref NPF occurring within a clade composed
      exclusively of arthropods.

PMID- 19747518
TI  - Ficus carica L.: Metabolic and biological screening.
AB  - Ficus carica L. is one of the earliest cultivated fruit trees. In this work,
      metabolite profiling was performed on the leaves, pulps and peels of two
      Portuguese white varieties of F. carica (Pingo de Mel and Branca Tradicional).
      Phenolics and organic acids profiles were determined by HPLC/DAD and HPLC/UV,
      respectively. All samples presented a similar phenolic profile composed by 3-O-
      and 5-O-caffeoylquinic acids, ferulic acid, quercetin-3-O-glucoside, quercetin-3
      O-rutinoside, psoralen and bergapten. 3-O-Caffeoylquinic acid and quercetin-3-O
      glucoside are described for the first time in this species. Leaves' organic acids
      profile presented oxalic, citric, malic, quinic, shikimic and fumaric acids,
      while in pulps and peels quinic acid was absent. The antioxidant potential of the
      different plant parts was checked. All materials exhibited activity against DPPH
      and nitric oxide radicals in a concentration-dependent way. However, only the
      leaves presented capacity to scavenge superoxide radical. Leaves were always the
      most effective part, which seems to be related with phenolics compounds.
      Additionally, acetylcholinesterase inhibitory capacity was evaluated, but no
      effect was observed. Antimicrobial potential was also assessed against several
      bacterial species, although no activity was noticed. This is the first study
      comparing the chemical composition and biological potential of F. carica pulps,
      peels and leaves.

PMID- 19747519
TI  - Assessment of the exposure to ochratoxin A in the province of Lleida, Spain.
AB  - Exposure to ochratoxin A (OTA) of 279 blood donors of nine localities of the
      province of Lleida (Spain) was assessed. OTA levels were detected in the blood
      plasma of the participants by HPLC-fluorescence detection with previous clean-up
      of the samples by immunoaffinity columns. Limit of detection was 0.075 ng/mL.
      Participants answered a questionnaire on consumption frequency of foods possibly
      contaminated with OTA. Foodstuffs were grouped: cereals and derived products,
      dried fruits and derived products, cacao and derived products, grape juice, wine,
      beer and coffee. The range of positive samples was 0.11-8.68 ng/mL and the median
      was 0.54 ng/mL. No differences were found between OTA plasma levels in men and
      women, neither in the different localities, but there were significant
      differences among three age groups. Highest consumed foods were cereals and
      derived products, followed by beer and wine. No correlation was found between
      food consumption and OTA plasma levels. OTA daily intake was estimated based on
      OTA plasma concentrations and on the food consumption data combined with food
      contamination data taken from the literature. Mean values were 1.69 and 1.96
      ng/kg body weight/day, respectively. These values are below the latest proposed
      tolerable daily intake of 14 ng/kg body weight/day.

PMID- 19747520
TI  - In vivo and in vitro skin absorption of lipophilic compounds, dibutyl phthalate,
      farnesol and geraniol in the hairless guinea pig.
AB  - The relationship between in vitro and in vivo skin absorption of lipophilic
      cosmetic ingredients (dibutyl phthalate (DBP, Log K(ow): 4.45), farnesol (Log
      K(ow): 5.77) and geraniol (Log K(ow): 3.56) from an oil-in-water emulsion was
      investigated in the hairless guinea pig. In vivo absorption of DBP, farnesol and
      geraniol 24h after dermal application was 62.0+/-2.0, 39.8+/-2.5, and 15.1+/-1.8%
      of the applied dose (%AD), respectively. In vitro absorption was measured at 24
      and 72 h by using flow-through diffusion cells (0.64 cm(2)) with a receptor fluid
      consisting of HHBSS+4% BSA. In vitro studies of DBP, farnesol and geraniol
      absorption over 24h found 27.1+/-1.9, 43.5+/-3.3 and 45.9+/-3.2%AD in receptor
      fluid, respectively, and over 72 h found 59.9+/-3.2, 77.5+/-7.1 and 49.0+/
      6.3%AD, respectively. We found that the amount of DBP absorbed in vivo after 24h
      closely agreed with the amount of DBP found in the receptor fluid in vitro after
      72 h. In contrast, the amount of topically applied farnesol absorbed in vivo
      after 24h was similar to the amount of farnesol found in receptor fluid in vitro
      after 24h. A direct comparison between the in vivo absorption of geraniol and the
      in vitro absorption at 24 and 72 h was not meaningful due to the rapid
      evaporation of geraniol from the skin. Our in vitro results suggest that
      lipophilic chemicals initially form a reservoir in skin, and the material in the
      reservoir may ultimately diffuse out of the skin into the receptor fluid within
      72 h. Our results also demonstrate the utility of in vivo studies for resolving
      questions about the fate of lipophilic chemicals remaining in skin after in vitro
      absorption studies.

PMID- 19747521
TI  - Schisandrin B stimulates a cytoprotective response in rat liver exposed to
      mercuric chloride.
AB  - Mercury represents an ubiquitous environmental toxic metal. Heat shock proteins
      (HSP) and metallothioneins (MTs) help to protect cells against metal toxicity.
      Schisandrin B (Sch B), a lignoid from Schisandra chinensis, has been successfully
      used to treat hepatitis, but its effect against mercury hepatotoxicity remains
      unknown. We analyzed whether Sch B could protect rat liver against mercuric
      chloride (HgCl2) intake by analyzing stress proteins and histopathological
      changes. Wistar rats were administered Sch B (10mg/kg/day by gavage) or vehicle
      (olive oil) for 10 days. A subset of each group also received low-dose HgCl2
      (0.1mg/kg/day) for 3 days on days 8-10. Another group received Sch B for 10 days
      with a single high dose of HgCl2 (1mg/kg intraperitoneally) on day 10. In rats
      treated with Sch B and HgCl2, HSP72, HSP25 and MTs were overexpressed in liver
      zones 1 and 3 irrespective of HgCl2 dosing schedules. Furthermore Sch B alone
      induced perinuclear rough endoplasmic reticulum alignment and if associated to
      HgCl2, increased mitochondrial density and dense bodies, all signs of intense
      detoxification machinery. Taking together these data suggest that dietary Sch B
      counteracts HgCl2 hepatotoxicity in the rat by stimulating chaperones responsible
      for anabolic activity.

PMID- 19747522
TI  - Nitrochalcones: potential in vivo insulin secretagogues.
AB  - In this study, the in vivo and in vitro anti-hyperglycemic activity of chalcone
      derivatives of 3,4-methylenedioxy, with a substituent electron-acceptor nitro
      group in the A or B ring, was investigated. As expected, the second generation
      sulfonylurea glipizide stimulated insulin secretion and reduced glycemia over the
      study period. Also, it was demonstrated for the first time that chalcones are
      able to increase insulin secretion and this event was coincident with serum
      glucose-lowering in the oral glucose tolerance test. Additionally, the chalcones
      studied had a similar effect on insulin secretion and serum glucose-lowering as
      glipizide. The effect of chalcones in terms of inducing insulin secretion was
      greater than that of glipizide after 30 min. Moreover, chalcones were not able to
      stimulate glucose uptake in soleus muscle, either in the presence of insulin or
      in the absence of this hormone. In addition, the oral treatment with chalcones
      did not alter glycemia in diabetic rats. These reports indicate that the effect
      of chalcones on serum glucose-lowering in hyperglycemic-normal rats is mainly a
      consequence of insulin secretion, highlighting these chalcones as novel compounds
      with strong anti-hyperglycemic properties.

PMID- 19747523
TI  - Reevaluation of the 2-deoxyribose assay for determination of free radical
      formation.
AB  - BACKGROUND: The 2-deoxyribose (2-DR) degradation assay is a widely used test for
      determining anti/pro-oxidant properties of molecules and plant extracts. Most
      reports use reaction blanks omitting 2-DR or thiobarbituric acid (TBA). However,
      when studying Fe(II)-mediated reactions, we verified that these blanks are not
      appropriate. Fe(III)--a product of these reactions--causes a relevant artifact in
      the assay, where 2-DR is oxidized by Fe(III). METHOD: 2-DR degradation was
      determined at 532 nm as TBA-reactive substances. RESULTS AND CONCLUSION: HPLC
      determinations indicated that Fe(III) added after or before TBA generates
      considerable amounts of malondialdehyde (2-DR degradation product) in comparison
      with assays employing Fenton reagents or Fe(II) autoxidation. Addition of
      catalase and thiourea has no effect on Fe(III)-induced 2-DR degradation
      indicating lack of ROS involvement. This Fe(III)-mediated 2-DR damage is
      dependent on iron and 2-DR concentrations, but not on H2O2, buffer composition or
      iron-chelators. Depending on the assay conditions Fe(III)-interference accounts
      for 20% to 90% of 2-DR degradation mediated by Fe(II). SIGNIFICANCE: A new
      reaction blank is proposed herein-based on the use of Fe(III)-for the assay. The
      lack of such correction has caused the underestimation of antioxidant capacity of
      various compounds in many studies in the last 2 decades.

PMID- 19747524
TI  - Interaction of heparin and heparin-derived oligosaccharides with synthetic
      peptide analogues of the heparin-binding domain of heparin/heparan sulfate
      interacting protein.
AB  - BACKGROUND: Although protamine is effective as an antidote of heparin, there is a
      need to replace protamine due to its side effects. HIP peptide has been reported
      to neutralize the anticoagulant activity of heparin. The interaction of HIP
      analog peptides with heparin and heparin-derived oligosaccharides is investigated
      in this paper. METHODS: Seven analogues of the heparin-binding domain of
      heparin/heparan sulfate-interacting protein (HIP) were synthesized, and their
      interaction with heparin was characterized by heparin affinity chromatography,
      isothermal titration calorimetry, and NMR. RESULTS: NMR results indicate the
      imidazolium groups of the His side chains of histidine-containing Hip analog
      peptide interact site-specifically with heparin at pH 5.5. Heparin has identical
      affinities for HIP analog peptides of opposite chirality. Analysis by counterion
      condensation theory indicates the peptide AC-SRPKAKAKAKAKDQTK-NH2 makes on
      average approximately 3 ionic interactions with heparin that result in
      displacement of approximately 2 Na+ ions, and ionic interactions account for
      approximately 46% of the binding free energy at a Na+ concentration of 0.15 M.
      CONCLUSIONS: The affinity of heparin for the peptides is strongly dependent on
      the nature of the cationic side chains and pH. The thermodynamic parameters
      measured for the interaction of HIP peptide analogs with heparin are strongly
      dependent on the peptide sequence and pH. GENERAL SIGNIFICANCE: The information
      obtained in this research will be of use in the design of new agents for
      neutralization of the anticoagulant activity of heparin. The site-specific
      binding of protonated histidine side chains to heparin provides a molecular-level
      explanation for the pH-dependent binding of beta-amyloid peptides by heparin and
      heparan sulfate proteoglycan and may have implications for amyloid formation.

PMID- 19747525
TI  - Angiotensin III modulates the nociceptive control mediated by the periaqueductal
      gray matter.
AB  - Endogenous angiotensin (Ang) II and/or an Ang II-derived peptide, acting on Ang
      type 1 (AT(1)) and Ang type 2 (AT(2)) receptors, can carry out part of the
      nociceptive control modulated by periaqueductal gray matter (PAG). However,
      neither the identity of this putative Ang-peptide, nor its relationship to Ang II
      antinociceptive activity was clarified. Therefore, we have used tail-flick and
      incision allodynia models combined with an HPLC time course of Ang metabolism, to
      study the Ang III antinociceptive effect in the rat ventrolateral (vl) PAG using
      peptidase inhibitors and receptor antagonists. Ang III injection into the vlPAG
      increased tail-flick latency, which was fully blocked by Losartan and CGP
      42,112A, but not by divalinal-Ang IV, indicating that Ang III effect was mediated
      by AT(1) and AT(2) receptors, but not by the AT(4) receptor. Ang III injected
      into the vlPAG reduced incision allodynia. Incubation of Ang II with punches of
      vlPAG homogenate formed Ang III, Ang (1-7) and Ang IV. Amastatin (AM) inhibited
      the formation of Ang III from Ang II by homogenate, and blocked the
      antinociceptive activity of Ang II injection into vlPAG, suggesting that
      aminopeptidase A (APA) formed Ang III from Ang II. Ang III can also be formed
      from Ang I by a vlPAG alternative pathway. Therefore, the present work shows, for
      the first time, that: (i) Ang III, acting on AT(1) and AT(2) receptors, can
      elicit vlPAG-mediated antinociception, (ii) the conversion of Ang II to Ang III
      in the vlPAG is required to elicit antinociception, and (iii) the antinociceptive
      activity of endogenous Ang II in vlPAG can be ascribed preponderantly to Ang III.

PMID- 19747526
TI  - Cellular prion protein modulates age-related behavioral and neurochemical
      alterations in mice.
AB  - The cellular prion protein (PrP(C)) is a neuronal-anchored glycoprotein that has
      been associated with various functions in the CNS such as synaptic plasticity,
      cognitive processes and neuroprotection. Here we investigated age-related
      behavioral and neurochemical alterations in wild-type (Prnp(+/+)), PrP(C)
      knockout (Prnp(0/0)) and the PrP(C) overexpressing Tg-20 mice. Three- or 11 month
      old animals were submitted to a battery of behavioral tasks including open field,
      activity cages, elevated plus-maze, social recognition and inhibitory avoidance
      tasks. The 11 month-old Prnp(+/+) and Prnp(0/0) mice exhibited significant
      impairments in their locomotor activity and social recognition memory and
      increased anxiety-related responses. Remarkably, Tg-20 mice did not present these
      age-related impairments. The i.c.v. infusion of STI1 peptide 230-245, which
      includes the PrP(C) binding site, improved the age-related social recognition
      deficits in Prnp(+/+). In comparison with the two other age-matched genotypes,
      the 11 month-old Tg-20 mice also exhibited reduced activity of seric
      acetylcholinesterase, increased expression of the protein synaptophysin and
      decreased caspase-3 positive-cells in the hippocampus. The present findings
      obtained with genetic and pharmacological approaches provide convincing evidence
      that PrP(C) exerts a critical role in the age-related behavioral deficits in mice
      probably through adaptive mechanisms including apoptotic pathways and synaptic
      plasticity.

PMID- 19747527
TI  - The subcellular distribution of aquaporin 5 in the cochlea reveals a water shunt
      at the perilymph-endolymph barrier.
AB  - Aquaporins are membrane water channel proteins that have also been identified in
      the cochlea. Auditory function critically depends on the homeostasis of the
      cochlear fluids perilymph and endolymph. In particular, the ion and water
      regulation of the endolymph is essential for sensory transduction. Within the
      cochlear duct the lateral wall epithelium has been proposed to secrete endolymph
      by an aquaporin-mediated flow of water across its epithelial tight junction
      barrier. This study identifies interspecies differences in the cellular
      distribution of aquaporin 5 (AQP5) in the cochlear lateral wall of mice, rats,
      gerbils and guinea pigs. In addition the cellular expression pattern of AQP5 is
      described in the human cochlea. Developmental changes in rats demonstrate
      longitudinal and radial gradients along the cochlear duct. During early postnatal
      development a pancochlear expression is detected. However a regression to the
      apical quadrant and limitation to outer sulcus cells (OSCs) is observed in the
      adult. This developmental loss of AQP5 expression in the basal cochlear segments
      coincides with a morphological loss of contact between OSCs and the endolymph. At
      the subcellular level, AQP5 exhibits polarized expression in the apical plasma
      membrane of the OSCs. Complementary, the basolateral membrane in the root
      processes of the OSCs exhibits AQP4 expression. This differential localization of
      AQP5 and AQP4 in the apical and basolateral membranes of the same epithelial cell
      type suggests a direct aquaporin-mediated transcellular water shunt between the
      perilymph and endolymph in the OSCs of the cochlear lateral wall. In the human
      cochlea these findings may have pathophysiological implications attributed to a
      dysfunctional water regulation by AQP5 such as endolymphatic hydrops (i.e. in
      Meniere's disease) or sensorineural hearing loss (i.e. in Sjogren's syndrome).

PMID- 19747528
TI  - Long adaptation reveals mostly attractive shifts of orientation tuning in cat
      primary visual cortex.
AB  - In the adult brain, sensory cortical neurons undergo transient changes of their
      response properties following prolonged exposure to an appropriate stimulus
      (adaptation). In cat V1, orientation-selective cells shift their preferred
      orientation after being adapted to a non-preferred orientation. There are
      conflicting reports as to the direction of those shifts, towards (attractive) or
      away (repulsive) from the adapter. Moreover, the mechanisms underlying attractive
      shifts remain unexplained. In the present investigation we show that attractive
      shifts are the most frequent outcome of a 12 min adaptation. Overall, cells
      displaying selectivity for oblique orientations exhibit significantly larger
      shifts than cells tuned to cardinal orientations. In addition, cells selective to
      cardinal orientations had larger shift amplitudes when the absolute difference
      between the original preferred orientation and the adapting orientation
      increased. Conversely, cells tuned to oblique orientations exhibited larger shift
      amplitudes when this absolute orientation difference was narrower. Hence, neurons
      tuned to oblique contours appear to show more plasticity in response to small
      perturbations. Two different mechanisms appear to produce attractive and
      repulsive orientation shifts. Attractive shifts result from concurrent response
      depression on the non-adapted flank and selective response facilitation on the
      adapted flank of the orientation tuning curve. In contrast, repulsive shifts are
      caused solely by response depression on the adapted flank. We suggest that an
      early mechanism leads to repulsive shifts while attractive shifts engage a
      subsequent late facilitation. A potential role for attractive shifts may be
      improved stimulus discrimination around the adapting orientation.

PMID- 19747529
TI  - Localization of multiple neurotransmitters in surgically derived specimens of
      human atrial ganglia.
AB  - Dysfunction of the intrinsic cardiac nervous system is implicated in the genesis
      of atrial and ventricular arrhythmias. While this system has been studied
      extensively in animal models, far less is known about the intrinsic cardiac
      nervous system of humans. This study was initiated to anatomically identify
      neurotransmitters associated with the right atrial ganglionated plexus (RAGP) of
      the human heart. Biopsies of epicardial fat containing a portion of the RAGP were
      collected from eight patients during cardiothoracic surgery and processed for
      immunofluorescent detection of specific neuronal markers. Colocalization of
      markers was evaluated by confocal microscopy. Most intrinsic cardiac neuronal
      somata displayed immunoreactivity for the cholinergic marker choline
      acetyltransferase and the nitrergic marker neuronal nitric oxide synthase. A
      subpopulation of intrinsic cardiac neurons also stained for noradrenergic
      markers. While most intrinsic cardiac neurons received cholinergic innervation
      evident as punctate immunostaining for the high affinity choline transporter,
      some lacked cholinergic inputs. Moreover, peptidergic, nitrergic, and
      noradrenergic nerves provided substantial innervation of intrinsic cardiac
      ganglia. These findings demonstrate that the human RAGP has a complex
      neurochemical anatomy, which includes the presence of a dual
      cholinergic/nitrergic phenotype for most of its neurons, the presence of
      noradrenergic markers in a subpopulation of neurons, and innervation by a host of
      neurochemically distinct nerves. The putative role of multiple neurotransmitters
      in controlling intrinsic cardiac neurons and mediating efferent signaling to the
      heart indicates the possibility of novel therapeutic targets for arrhythmia
      prevention.

PMID- 19747530
TI  - Drug therapies for attentional disorders alter the signal-to-noise ratio in the
      superior colliculus.
AB  - Despite high levels of use, the mechanism of action of effective
      pharmacotherapies in attention deficit hyperactivity disorder (ADHD) is unknown.
      It has recently been hypothesized that one site of therapeutic action is the
      midbrain superior colliculus, a structure traditionally associated with visual
      processing, but also strongly implicated in distractibility, a core symptom of
      ADHD. We used male juvenile Wistar rats to examine the effects of therapeutically
      relevant doses of methylphenidate and d-amphetamine on collicular activity in
      vitro. Here we report a novel shared mechanism of the two drugs whereby they
      enhance the signal-to-noise ratio in the superior colliculus. The effects on the
      signal-to-noise ratio were mediated by serotonin (5-HT) via a pre-synaptic
      mechanism. This modulatory action would bias the system towards salient events
      and lead to an overall decrease in distractibility.

PMID- 19747531
TI  - Cellular organization of the central canal ependymal zone, a niche of latent
      neural stem cells in the adult mammalian spinal cord.
AB  - A stem cell's microenvironment, or "niche," is a critical regulator of its
      behaviour. In the adult mammalian spinal cord, central canal ependymal cells
      possess latent neural stem cell properties, but the ependymal cell niche has not
      yet been described. Here, we identify important similarities and differences
      between the central canal ependymal zone and the forebrain subventricular zone
      (SVZ), a well-characterized niche of neural stem cells. First, direct
      immunohistochemical comparison of the spinal cord ependymal zone and the
      forebrain SVZ revealed distinct patterns of neural precursor marker expression.
      In particular, ependymal cells in the spinal cord were found to be bordered by a
      previously uncharacterized sub-ependymal layer, which is relatively less
      elaborate than that of the SVZ and comprised of small numbers of astrocytes,
      oligodendrocyte progenitors and neurons. Cell proliferation surrounding the
      central canal occurs in close association with blood vessels, but unlike in the
      SVZ, involves mainly ependymal rather than sub-ependymal cells. These
      proliferating ependymal cells typically self-renew rather than produce transit
      amplifying progenitors, as they generate doublets of progeny that remain within
      the ependymal layer and show no evidence of a lineage relationship to sub
      ependymal cells. Interestingly, the dorsal pole of the central canal was found to
      possess a sub-population of tanycyte-like cells that express markers of both
      ependymal cells and neural precursors, and their presence correlates with higher
      numbers of dorsally proliferating ependymal cells. Together, these data identify
      key features of the spinal cord ependymal cell niche, and suggest that dorsal
      ependymal cells possess the potential for stem cell activity. This work provides
      a foundation for future studies aimed at understanding ependymal cell regulation
      under normal and pathological conditions.

PMID- 19747532
TI  - Unique genome of dicyemid mesozoan: highly shortened spliceosomal introns in
      conservative exon/intron structure.
AB  - Dicyemids are enigmatic endoparasites, or endosymbionts, living in the renal sac
      of benthic cephalopod molluscs. The body of dicyemids consists of only 9-41
      cells, with neither extracellular matrices nor differentiated tissues. Due to the
      unusually simple body organization, dicyemids have long been the subject of
      phylogenetic controversy. Molecular evidences suggest dicyemids are
      lophotrochozoans that have secondarily lost many morphological characters. We
      studied 40 genes of the dicyemid Dicyema japonicum and found that their
      spliceosomal introns are very short (mean length=26 bp). This size was shorter
      than that of introns of animals, such as Fugu rubripes and Oikopleura dioica
      which possess compact genome and introns. In the intron size, the dicyemid was
      nearly equal to the chlorarachniophyte Bigelowiella natans nucleomorph (18-21 bp)
      which has the shortest introns of any known eukaryote. Despite the short introns,
      the intron density (5.3 introns/gene) of the dicyemid is similar to that in model
      invertebrates. In addition, the exon/intron structure of the dicyemid is more
      similar to vertebrates than to the model invertebrates. These results suggest
      that the positions of the introns are possibly conserved under functional
      constraints.

PMID- 19747533
TI  - The role of metabotropic glutamate receptor 5 in developmental lead
      neurotoxicity.
AB  - A complete explanation of the mechanisms of lead-induced developmental
      neurotoxicity remains unknown. The glutamate receptor is one of the most
      important targets of lead. More recently, metabotropic glutamate receptor 5
      (mGluR5) has been shown to have a functional relationship with learning and
      memory. We investigated the impact of developmental lead exposure on hippocampal
      mGluR5 expression and its potential role in lead neurotoxicity. Both in vitro
      model of lead exposure with Pb(2+) concentrations of 0, 10 nM, 1 microM, and 100
      microM in cultured rat embryonic hippocampal neurons, and the in vivo model of
      rat maternal lead exposure involving both gestational and lactational exposure
      with 0, 0.05%, 0.2%, and 0.5% lead acetate were utilized. Immunoperoxidase and
      immunofluorescent analyses, quantitative PCR and western blotting were used. In
      vitro studies revealed that expression of mGluR5 mRNA and protein was decreased
      dose-dependently after lead exposure, which was further confirmed by the results
      of in vivo studies. These data suggest that mGluR5 might be involved in lead
      induced neurotoxicity by disturbing mGluR5-induced long-term depression and
      decreasing N-methyl-D-aspartic acid receptor (NMDAR)-dependent or protein
      synthesis-dependent long-term potentiation. These results might improve the
      understanding of the mechanism and potential treatments for moderate to severe
      lead poisoning in children.

PMID- 19747534
TI  - Brucella abortus induces Irgm3 and Irga6 expression via type-I IFN by a MyD88
      dependent pathway, without the requirement of TLR2, TLR4, TLR5 and TLR9.
AB  - The innate immune system senses bacterial pathogens by pattern recognition
      receptors, such as the well-characterised Toll-like Receptors (TLR). The
      activation of TLR signalling cascades depends on several adaptor proteins, among
      which MyD88 plays a key role in triggering innate immune responses. Here, we show
      in murine macrophages that Brucella abortus triggers expression of the interferon
      inducible resistance proteins (IRGs, p47 GTPases) via type-I IFN secretion at
      late time points, when Brucella has reached its replication niche. This induction
      requires the adaptor molecule MyD88 but does not involve the TLRs normally
      implicated in sensing Gram-negative bacteria, namely TLR2, TLR4, TLR5 and TLR9.
      Brucella mutants lacking the functional VirB type-IV secretion system were not
      capable of inducing Irgm3 and Irga6 expression, suggesting that the type-IV
      secretion system is part of the triggering of the activation process. Our data
      suggest that Brucella is recognized intracellularly by an unknown receptor,
      different from the conventional ones used for Gram-negative sensing, but one that
      nevertheless signals through MyD88.

PMID- 19747535
TI  - An in vitro micronucleus assay with size-classified micronucleus counting to
      discriminate aneugens from clastogens.
AB  - In the in vitro micronucleus (MN) assay, genotoxic chemicals can be characterized
      as aneugens and clastogens by the presence and absence of kinetochore protein or
      centromere regions in the micronuclei, respectively. Aneugens preferentially
      induce kinetochore- or centromere-positive micronuclei which can be detected by
      the immunofluorescence staining method or the fluorescence in situ hybridization
      (FISH) method. Both methods are robust and reliable; however, these assays
      require a definite period of time and cost to obtain a result that suggests that
      the genotoxic chemicals cause aneuploidy. This is why these methods are not
      adequate to evaluate dozens of chemicals which are mixtures of aneugens and
      clastogens. To evaluate a batch of chemicals, a quicker and more convenient assay
      is desirable. In the present study, we examined whether the size-classified
      counting of MN is as effective as the FISH method to characterize aneuploidy in
      the in vitro MN assay using Chinese hamster lung (CHL) cell lines. As aneugens, 9
      substances (colcemid, vincristine sulfate, paclitaxel, thiabendazole,
      diethylstilbestrol, griseofulvin, bisphenol A, fisetin and okadaic acid) were
      used; as clastogens 6 substances (methylmethane sulfonate, N-methyl-N'-nitro-N
      nitroso-guanidine, etoposide, mitomycin C, hydroxyurea and actinomycin D) were
      used. The size-classified counting revealed that all the 9 aneugens increased
      both the frequency and proportion of large-size MN as compared with the vehicle
      control. Although N-methyl-N'-nitro-N-nitroso-guanidine, etoposide and mitomycin
      C increased the frequency, no increase was observed in the proportion. Meanwhile,
      with the FISH method, all the aneugens induced centromere-positive micronuclei
      but the clastogens did not. Based on these results, it is considered that the
      frequency of large-size MN in the in vitro MN assay is an alerting index for
      aneugenic effects and that its proportion is a simple and reliable index which is
      as effective as the FISH analysis for discrimination of aneugens from clastogens.

PMID- 19747536
TI  - The in vitro genotoxicity of ethanol and acetaldehyde.
AB  - Ability of ethanol to produce chromosomal changes has been controversial in past
      many years; nevertheless many recent studies have shown that ethanol itself
      produces genotoxic effects like acetaldehyde. This study was carried out to
      evaluate the ability of ethanol and its metabolite acetaldehyde to induce
      chromosomal changes using in vitro CBMN assay (Cytokinesis Blocked Micronucleus
      assay) in conjunction with immunofluorescent labeling of kinetochores.
      Kinetochore staining was used with a view to differentiate, between the genotoxic
      effects of both chemicals, and ascertain the mechanisms of genotoxicity induction
      by ethanol and acetaldehyde. Both ethanol and acetaldehyde produced statistically
      significant (P<0.05) dose dependent increase in MN induction as compared with the
      controls over the dose range tested. Kinetochore analysis proved that the MN
      induced in ethanol were originated by an aneugenic mechanism, whereas in the case
      of acetaldehyde most of the MN had originated by a clastogenic mechanism. This
      not only confirms the ability of ethanol to produce DNA damage in vitro but it
      also establishes the efficacy of CBMN assay to detect and differentiate between
      the genotoxic effects of different genotoxins. Here we report that ethanol is
      itself genotoxic, at least in vitro, and produces genotoxic effects mainly
      through an aneugenic mechanism whereas its metabolite acetaldehyde is a
      clastogen.

PMID- 19747537
TI  - Comparative in vitro and ex-vivo myelotoxicity of aflatoxins B1 and M1 on
      haematopoietic progenitors (BFU-E, CFU-E, and CFU-GM): species-related
      susceptibility.
AB  - Haemato- and myelotoxicity are adverse effects caused by mycotoxins. Due to the
      relevance of aflatoxins to human health, the present study, employing CFU-GM-,
      BFU-E- and CFU-E-clonogenic assays, aimed at (i) comparing, in vitro, the
      sensitivity of human vs. murine haematopoietic progenitors to AFB1 and AFM1
      (0.001-50microg/ml), (ii) assessing whether a single AFB1 in vivo treatment (0.3
      3mg/kgb.w.) alters the ability of murine bone marrow cells to form myeloid and
      erythroid colonies, and (iii) comparing the in vitro with the in vitro ex-vivo
      data. We demonstrated (i) species-related sensitivity to AFB1, showing higher
      susceptibility of human myeloid and erythroid progenitors (IC(50) values: about 4
      times lower in human than in murine cells), (ii) higher sensitivity of CFU-GM and
      BFU-E colonies, both more markedly affected, particularly by AFB1 (IC(50): 2.45+/
      1.08 and 1.82+/-0.8microM for humans, and 11.08+/-2.92 and 1.81+/-0.20microM for
      mice, respectively), than the mature CFU-E (AFB1 IC(50): 12.58+/-5.4 and 40.27+/
      6.05microM), irrespectively of animal species, (iii) regarding AFM1, a species-
      and lineage-related susceptibility similar to that observed for AFB1 and (iv)
      lack of effects after AFB1 in vivo treatment on the proliferation of
      haematopoietic colonies.

PMID- 19747538
TI  - Differential effects of herbicides atrazine and fenoxaprop-ethyl, and
      insecticides diazinon and malathion, on viability and maturation of porcine
      oocytes in vitro.
AB  - Exposure to pesticides may be a major cause of reproductive dysfunction in humans
      and animals. Atrazine and fenoxaprop-ethyl, widely used herbicides, and malathion
      and diazinon, organophosphate insecticides, are considered only slightly toxic to
      vertebrates; however, there is evidence of greater effects on reproductive
      function. The aim of this study was to evaluate the effect of these pesticides on
      oocyte viability and in vitro maturation. Gametes were matured in increasing
      concentrations of the pesticides and then stained with MTT to evaluate viability
      and bisbenzimide to assess the maturation stage, in the same oocyte. Atrazine had
      no effect on viability but maturation was significantly reduced, while fenoxaprop
      ethyl affected both parameters. The insecticides affected viability and
      maturation but to a different degree. The four pesticides showed a more
      pronounced effect on maturation than on viability, due to a blockage at germinal
      vesicle stage.

PMID- 19747539
TI  - Naphtho[1,2-b]furan-4,5-dione induces apoptosis and S-phase arrest of MDA-MB-231
      cells through JNK and ERK signaling activation.
AB  - Naphtho[1,2-b]furan-4,5-dione (NFD), prepared from 2-hydroxy-1,4-naphthoquinone
      and chloroacetaldehyde in an efficient one-pot reaction, exhibits anti
      carcinogenic effect. The results of present study showed that NFD inhibited the
      proliferation of breast cancer MDA-MB-231 cells through the induction of S-phase
      arrest and apoptosis. NFD-induced S-phase arrest was associated with a marked
      decrease in the protein expression of cyclin A, cyclin B, and cyclin-dependent
      kinase (Cdk)2. NFD-induced apoptosis was characterized by increase of sub-G1
      population, phosphatidylserine (PS) externalization, and activation of caspases.
      Moreover, up-regulation of Bad and down-regulation of Bcl-2, Bcl-X(L), and
      survivin led to the loss of mitochondrial membrane potential (DeltaPsim), the
      release of cytochrome c and sequential activation of caspase-9 and caspase-3. NFD
      activated c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase
      (p38 MAPK) and extracellular signal-regulated kinase (ERK) in MDA-MB-231 cells.
      Inhibitors of JNK (SP600125) and ERK (PD98059), but not p38 MAPK (SB203580)
      suppressed NFD-induced S-phase arrest and apoptosis in MDA-MB-231 cells. Both
      SP600125 and PD98059 attenuated Bad up-regulation, and reversed down-regulation
      of Bcl-2, Bcl-X(L), survivin, cyclin A, cyclin B, and Cdk2 in NFD-treated cells.
      Taken together, our data show that JNK and ERK-signaling pathways play important
      roles in NFD-mediated S-phase arrest and apoptosis of MDA-MB-231 cells.

PMID- 19747540
TI  - Improved gene targeting in C. elegans using counter-selection and Flp-mediated
      marker excision.
AB  - Gene targeting is widely used for the precise manipulation of genes. However, in
      the model organism Caenorhabditis elegans non-transposon mediated gene targeting
      remains laborious, and as a result has not been widely used. One obstacle to the
      wider use of this approach is the difficulty of identifying homologous
      recombination events amongst non-specific events. To improve gene targeting in C.
      elegans, we used a counter-selection approach to reduce the number of false
      positives; this involved using unc-119 as a positive-selection marker and GFP as
      a counter-selection marker which is lost during homologous recombination. This
      method of gene targeting allows straightforward screening for homologous events
      using a dissecting microscope equipped for fluorescence. In addition, to improve
      the final engineered product, we utilised Flp recombinase to remove the unc-119
      selection marker, in somatic cells, producing clean knockouts in these cells.
      Using this strategy we have produced a knockout of the plc-4 gene, which encodes
      phospholipase C-delta in C. elegans, and demonstrated that conditional gene
      knockout is feasible in C. elegans.

PMID- 19747541
TI  - Bacterial genomic G+C composition-eliciting environmental adaptation.
AB  - Bacterial genomes reflect their adaptation strategies through nucleotide usage
      trends found in their chromosome composition. Bacteria, unlike eukaryotes contain
      a wide range of genomic G+C. This wide variability may be viewed as a response to
      environmental adaptation. Two overarching trends are observed across bacterial
      genomes, the first, correlates genomic G+C to environmental niches and lifestyle,
      while the other utilizees intra-genomic G+C incongruence to delineate
      horizontally transferred material. In this review, we focus on the influence of
      several properties including biochemical, genetic flows, selection biases, and
      the biochemical-energetic properties shaping genome composition. Outcomes
      indicate a trend toward high G+C and larger genomes in free-living organisms, as
      a result of more complex and varied environments (higher chance for horizontal
      gene transfer). Conversely, nutrient limiting and nutrient poor environments
      dictate smaller genomes of low GC in attempts to conserve replication expense.
      Varied processes including translesion repair mechanisms, phage insertion and
      cytosine degradation has been shown to introduce higher AT in genomic sequences.
      We conclude the review with an analysis of current bioinformatics tools seeking
      to elicit compositional variances and highlight the practical implications when
      using such techniques.

PMID- 19747542
TI  - Simultaneous monitoring of drug and solvent diffusion across a model membrane
      using ATR-FTIR spectroscopy.
AB  - Attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy
      has been used to simultaneously follow the diffusion of model drugs and solvent
      across polydimethylsiloxane (silicone) membrane. Three model drugs, cyanophenol
      (CNP), methyl nicotinate (MN) and butyl paraben (BP) were selected to cover a
      range of lipophilicities. Isostearyl isostearate (ISIS) was chosen as the solvent
      because its large molecular weight should facilitate observation of whether the
      drug molecules are able to diffuse through the membrane independently of the
      solvent. The diffusion of the three drugs and the solvent was successfully
      described by a Fickian model. The effects of parameters such as the absorption
      wavelength used to follow diffusion on the calculated diffusion coefficient were
      investigated. Absorption wavelength which affects the depth of penetration of the
      infrared radiation into the membrane did not significantly affect the calculated
      diffusion coefficient over the wavelength range tested. Each of the model drugs
      was observed to diffuse independently of the solvent across the membrane. The
      diffusion of a CNP-ISIS hydrogen bonded complex across the membrane was also
      monitored. The relative diffusion rates of the solute and solvent across the
      membrane can largely be accounted for by the molecular size of the permeant.

PMID- 19747544
TI  - Altered profiles of gene expression in curcumin-treated rats with experimentally
      induced myocardial infarction.
AB  - Curcumin has extensive cardioprotective effects against diabetic cardiovascular
      complications, cardiac hypertrophy and myocardial infarction (MI), but the
      molecular mechanism behind such cardioprotective effects remains still unclear.
      To explore the mechanism of MI, a rat model of coronary artery ligation was used
      to assess the cardioprotective effects of curcumin. Microarray technology was
      employed to detect the gene expression in the heart of MI rats treated with
      curcumin. Semiquantitative RT-PCR was then performed to verify the microarray
      result. Our results showed that curcumin could improve heart function, diminish
      infarct size and reverse the abnormal changes in the activities of serum lactate
      dehydrogenase and creatine kinase MB in rats after MI. A total of 179 genes were
      found to be significantly differentially expressed between sham-operated rats and
      coronary artery-ligated rats. Cytokine-cytokine receptor interaction, ECM
      receptor interaction, focal adhesions and colorectal cancer pathway may be
      involved in the cardioprotective effects of curcumin.

PMID- 19747545
TI  - Engineering BspQI nicking enzymes and application of N.BspQI in DNA labeling and
      production of single-strand DNA.
AB  - BspQI is a thermostable Type IIS restriction endonuclease (REase) with the
      recognition sequence 5'GCTCTTC N1/N4 3'. Here we report the cloning and
      expression of the bspQIR gene for the BspQI restriction enzyme in Escherichia
      coli. Alanine scanning of the BspQI charged residues identified a number of DNA
      nicking variants. After sampling combinations of different amino acid
      substitutions, an Nt.BspQI triple mutant (E172A/E248A/E255K) was constructed with
      predominantly top-strand DNA nicking activity. Furthermore, a triple mutant of
      BspQI (Nb.BspQI, N235A/K331A/R428A) was engineered to create a bottom-strand
      nicking enzyme. In addition, we demonstrated the application of Nt.BspQI in
      optical mapping of single DNA molecules. Nt or Nb.BspQI-nicked dsDNA can be
      further digested by E. coli exonuclease III to create ssDNA for downstream
      applications. BspQI contains two potential catalytic sites: a top-strand
      catalytic site (Ct) with a D-H-N-K motif found in the HNH endonuclease family and
      a bottom-strand catalytic site (Cb) with three scattered Glu residues. BlastP
      analysis of proteins in GenBank indicated a putative restriction enzyme with
      significant amino acid sequence identity to BspQI from the sequenced bacterial
      genome Croceibacter atlanticus HTCC2559. This restriction gene was amplified by
      PCR and cloned into a T7 expression vector. Restriction mapping and run-off DNA
      sequencing of digested products from the partially purified enzyme indicated that
      it is an EarI isoschizomer with 6-bp recognition, which we named CatHI (CTCTTC
      N1/N4).

PMID- 19747546
TI  - Over-producing soluble protein complex and validating protein-protein interaction
      through a new bacterial co-expression system.
AB  - Many proteins exert their functions through a protein complex and protein-protein
      interactions. However, the study of these types of interactions is complicated
      when dealing with toxic or hydrophobic proteins. It is difficult to use the
      popular Escherichia coli host for their expression, as these proteins in all
      likelihood require a critical partner protein to ensure their proper folding and
      stability. In the present study, we have developed a novel co-expression vector,
      pHEX, which is compatible with, and thus can be partnered with, many commercially
      available E. coli vectors, such as pET, pGEX and pMAL. The pHEX contains the p15A
      origin of replication and a T7 promoter, which can over-produce a His-tagged
      recombinant protein. The new co-expression system was demonstrated to efficiently
      co-produce and co-purify heterodimeric protein complexes, for example PE25/PPE41
      (Rv2430c/Rv2431c) and ESAT6/CFP10 (Rv3874/Rv3875), from the human pathogen
      Mycobacterium tuberculosis H37Rv. Furthermore, the system was also effectively
      used to characterize protein-protein interactions through convenient affinity
      tags. Using an in vivo pull-down assay, for the first time we have confirmed the
      presence of three pairs of PE/PPE-related novel protein interactions in this
      pathogen. In summary, a convenient and efficient co-expression vector system has
      been successfully developed. The new system should be applicable to any protein
      complex or any protein-protein interaction of interest in a wide range of
      biological organisms.

PMID- 19747547
TI  - Cloning and purification of recombinant proteins of Mycoplasma hyopneumoniae
      expressed in Escherichia coli.
AB  - Mycoplasma hyopneumoniae, the etiological agent of swine enzootic pneumonia, is
      an important pathogen in the swine industry worldwide. Vaccination is the most
      cost-effective strategy for controlling and prevention of this disease. However,
      investigations on pathogenicity mechanisms as well as current serological
      detection methods and the development of new recombinant subunit vaccines are
      hampered by the lack of known and well characterized species-specific M.
      hyopneumoniae antigens. In this work, 54 predicted genes encoding proteins with
      potential to be used as subunit vaccine or antigens in diagnostic tests were
      selected, amplified by PCR and cloned into Escherichia coli expression vectors.
      Recombinant protein expression, solubility and yields were analyzed. The majority
      of the recombinant proteins were expressed in inclusion bodies. After
      solubilization with urea or N-lauroyl sarcosine, recombinant proteins were
      purified by Ni(2+) affinity chromatography. This approach allowed purification of
      thirty recombinant M. hyopneumoniae proteins which will be evaluated as vaccine
      candidates and/or as antigens to be used in diagnostic tests.

PMID- 19747548
TI  - Quantification of compression wood severity in tracheids of Pinus radiata D. Don
      using confocal fluorescence imaging and spectral deconvolution.
AB  - Confocal fluorescence microscopy was used to examine the spectral characteristics
      of lignin autofluorescence in secondary cell walls of normal and compression wood
      from Pinus radiata. Using UV excitation, fluorescence spectra of normal and
      compression wood sections showed significant differences, especially in the outer
      secondary cell wall of tracheids, with a shift in maxima from violet to blue
      wavelengths between normal and compression wood. A comparison of normal wood,
      mild and severe compression wood, showed that the wavelength shift was
      intermediate in the mild compression wood compared to the severe compression
      wood, thus offering the possibility of quantifying the severity by measuring
      ratios of fluorescence at violet and blue wavelengths. Fluorescence induced by
      blue light, rather than UV, was less well differentiated amongst wood types.
      Spectral deconvolution indicated the presence of a minimum of five discrete
      lignin fluorophores in the cell walls of both normal and compression wood
      tracheids. Comparison with lignin model compounds suggest that the wavelength
      shift may correspond in part to increased levels of p-hydroxy type lignin in the
      compression wood samples. The combination of confocal fluorescence imaging and
      related spectral deconvolution therefore offers a novel technique for
      characterising cell wall lignin in situ.

PMID- 19747549
TI  - Molecular dynamics simulations investigation of neocarzinostatin chromophore
      releasing pathways from the holo-NCS protein.
AB  - The enediyne ring chromophore with strong DNA cleavage activity of
      neocarzinostatin is labile and therefore stabilization by forming the complex
      (carrying protein+chromophore: holo-NCS). Holo-NCS has gained much attention in
      clinical use as well as for drug delivery systems, but the chromophore-releasing
      mechanism to trigger binding to the target DNA with high affinity and producing
      DNA damage remain unclear. Three possible pathways were initially determined by
      conventional MD, essential dynamics and essential dynamics sampling. One of the
      paths runs along the naphthoate moiety; another runs along the amino sugar
      moiety; the third along the enediyne ring. Further, calculated forces and time by
      FPMD (force-probe molecular dynamics) suggest that the opening of the naphthoate
      moiety is most favorable pathway and Leu45, Phe76 and Phe78 all are key residues
      for chromophore release. In addition, conformational analyses indicate that the
      chromophore release is only local motions for the protein.

PMID- 19747550
TI  - Structure of the Pseudomonas aeruginosa XcpT pseudopilin, a major component of
      the type II secretion system.
AB  - The bacterial type II protein secretion (T2S) and type IV piliation (T4P) systems
      share several common features. In particular, it is well established that the T2S
      system requires the function of a pilus-like structure, called pseudopilus, which
      is built upon assembly of pilin-like subunits, called pseudopilins. Pilins and
      pseudopilins have a hydrophobic N-terminal region, which precedes an extended
      hydrophilic C-terminal region. In the case of pilins, it was shown that
      oligomerisation and formation of helical fibers, takes place through interaction
      between the hydrophobic domains. XcpT, is the most abundant protein of the
      Pseudomonas aeruginosa T2S, and was proposed to be the main component in the
      pseudopilus. In this study we present the high-resolution NMR structure of the
      hydrophilic domain of XcpT (XcpTp). XcpTp is lacking the C-terminal disulfide
      bridged "D" domain found in type IV pilins and likely involved in receptor
      binding. This is in agreement with the idea that the XcpT-containing pseudopilus
      is required for protein secretion and not for bacterial attachment.
      Interestingly, by solving the 3D structure of XcpTp we revealed that the
      previously called alphabeta-loop pilin region is in fact highly conserved among
      major type II pseudopilins and constitutes a specific consensus motif for
      identifying major pseudopilins, which belong to this family.

PMID- 19747551
TI  - A morphological analysis of growth cones of DRG neurons combining atomic force
      and confocal microscopy.
AB  - We have analyzed the morphology of growth cones of differentiating neurons from
      rat dorsal root ganglia (DRG) with conventional Laser Scanning Confocal
      Microscopy (LSCM) and Atomic Force Microscopy (AFM). Images of immunofluorescent
      DRG growth cones colabeled for actin and tubulin were superimposed to images
      obtained with AFM at different scanning forces. In order to reduce changes of the
      image surface caused by the pressure of the AFM tip, we have developed a
      procedure to obtain 0pN AFM images. Further analysis of these images revealed
      topographical structures with nanoscale dimensions, referred to as
      "invaginations" or "holes". These holes had an area varying from 0.01 to 3.5
      microm(2) with a depth varying from 2 to 178 nm. Comparative analysis with LSCM
      images showed that these holes correspond to regions where staining of both actin
      and tubulin was negligible. Filopodia height varied from 40 to 270 nm and their
      diameter from 113 to 887 nm. These results show that the combination of LSCM and
      AFM reveal structural details with a nanoscale dimension of DRG growth cones,
      difficult to resolve with conventional microscopy.

PMID- 19747552
TI  - Six problems for causal inference from fMRI.
AB  - Neuroimaging (e.g. fMRI) data are increasingly used to attempt to identify not
      only brain regions of interest (ROIs) that are especially active during
      perception, cognition, and action, but also the qualitative causal relations
      among activity in these regions (known as effective connectivity; Friston, 1994).
      Previous investigations and anatomical and physiological knowledge may somewhat
      constrain the possible hypotheses, but there often remains a vast space of
      possible causal structures. To find actual effective connectivity relations,
      search methods must accommodate indirect measurements of nonlinear time series
      dependencies, feedback, multiple subjects possibly varying in identified regions
      of interest, and unknown possible location-dependent variations in BOLD response
      delays. We describe combinations of procedures that under these conditions find
      feed-forward sub-structure characteristic of a group of subjects. The method is
      illustrated with an empirical data set and confirmed with simulations of time
      series of non-linear, randomly generated, effective connectivities, with
      feedback, subject to random differences of BOLD delays, with regions of interest
      missing at random for some subjects, measured with noise approximating the signal
      to noise ratio of the empirical data.

PMID- 19747553
TI  - Development of cerebral fiber pathways in cats revealed by diffusion spectrum
      imaging.
AB  - Examination of the three-dimensional axonal pathways in the developing brain is
      key to understanding the formation of cerebral connectivity. By tracing fiber
      pathways throughout the entire brain, diffusion tractography provides information
      that cannot be achieved by conventional anatomical MR imaging or histology.
      However, standard diffusion tractography (based on diffusion tensor imaging, or
      DTI) tends to terminate in brain areas with low water diffusivity, indexed by low
      diffusion fractional anisotropy (FA), which can be caused by crossing fibers as
      well as fibers with less myelin. For this reason, DTI tractography is not
      effective for delineating the structural changes that occur in the developing
      brain, where the process of myelination is incomplete, and where crossing fibers
      exist in greater numbers than in the adult brain. Unlike DTI, diffusion spectrum
      imaging (DSI) can define multiple directions of water diffusivity; as such,
      diffusion tractography based on DSI provides marked flexibility for delineation
      of fiber tracts in areas where the fiber architecture is complex and
      multidirectional, even in areas of low FA. In this study, we showed that FA
      values were lower in the white matter of newborn (postnatal day 0; P0) cat brains
      than in the white matter of infant (P35) and juvenile (P100) cat brains. These
      results correlated well with histological myelin stains of the white matter: the
      newborn kitten brain has much less myelin than that found in cat brains at later
      stages of development. Using DSI tractography, we successfully identified
      structural changes in thalamo-cortical and cortico-cortical association tracts in
      cat brains from one stage of development to another. In newborns, the main body
      of the thalamo-cortical tract was smooth, and fibers branching from it were
      almost straight, while the main body became more complex and branching fibers
      became curved reflecting gyrification in the older cats. Cortico-cortical tracts
      in the temporal lobe were smooth in newborns, and they formed a sharper angle in
      the later stages of development. The cingulum bundle and superior longitudinal
      fasciculus became more visible with time. Within the first month after birth,
      structural changes occurred in these tracts that coincided with the formation of
      the gyri. These results show that DSI tractography has the potential for mapping
      morphological changes in low FA areas associated with growth and development. The
      technique may also be applicable to the study of other forms of brain plasticity,
      including future studies in vivo.

PMID- 19747554
TI  - Reduced variance in monozygous twins for multiple MR parameters: implications for
      disease studies and the genetic basis of brain structure.
AB  - Twin studies offer the opportunity to determine the relative contribution of
      genes versus environment in traits of interest. Here, we investigate the extent
      to which variance in brain structure is reduced in monozygous twins with
      identical genetic make-up. We investigate whether using twins as compared to a
      control population reduces variability in a number of common magnetic resonance
      (MR) structural measures, and we investigate the location of areas under major
      genetic influences. This is fundamental to understanding the benefit of using
      twins in studies where structure is the phenotype of interest. Twenty-three pairs
      of healthy MZ twins were compared to matched control pairs. Volume, T2 and
      diffusion MR imaging were performed as well as spectroscopy (MRS). Images were
      compared using (i) global measures of standard deviation and effect size, (ii)
      voxel-based analysis of similarity and (iii) intra-pair correlation. Global
      measures indicated a consistent increase in structural similarity in twins. The
      voxel-based and correlation analyses indicated a widespread pattern of increased
      similarity in twin pairs, particularly in frontal and temporal regions. The areas
      of increased similarity were most widespread for the diffusion trace and least
      widespread for T2. MRS showed consistent reduction in metabolite variation that
      was significant in the temporal lobe N-acetylaspartate (NAA). This study has
      shown the distribution and magnitude of reduced variability in brain volume,
      diffusion, T2 and metabolites in twins. The data suggest that evaluation of twins
      discordant for disease is indeed a valid way to attribute genetic or
      environmental influences to observed abnormalities in patients since evidence is
      provided for the underlying assumption of decreased variability in twins.

PMID- 19747555
TI  - Silencing of calpain expression reduces the metastatic potential of human
      osteosarcoma cells.
AB  - Osteosarcoma, the most common primary bone tumor in young adults, is
      characterized by local invasion and distant metastasis. But detailed mechanisms
      of tumorigenicity and metastasis of osteosarcoma are not well known. We report
      the involvement of calpains, a family of calcium-activated, cysteine proteases,
      in the invasive and metastatic processes of human osteosarcoma cells. By using
      siRNA treatment, the expression of mu- and m-calpains were downregulated in human
      Saos-2 osteosarcoma cells. Both the adhesive and invasive potentials were
      significantly attenuated in calpain siRNA-transfected human Saos-2 osteosarcoma
      cells. MMPs are the main factors involved in malignant tumor invasion and
      metastasis. siRNA of calpains also significantly inhibited the secretion of MMP-2
      in Saos-2 cells. These results suggest that mu- and m-calpains are important in
      the invasion and metastasis of human osteosarcoma cells, and calpains might be
      targeted to reduce tumor progression.

PMID- 19747556
TI  - Patient-reported outcomes for acute graft-versus-host disease prevention and
      treatment trials.
AB  - Patient-reported outcomes (PROs) such as health-related quality of life,
      functional status, and symptom burden have been recognized by the U.S. Food and
      Drug Administration (FDA) as legitimate measures of clinical benefit for sponsors
      seeking drug approval. However, in practice, very few agents have been approved
      based on these endpoints. Successful use of PROs in registration trials requires
      rigorous methods to overcome numerous logistic and analytic barriers. Acute graft
      versus-host disease (aGVHD) is associated with high morbidity and mortality, and
      its prevention and treatment are the goals of many clinical trials in the
      hematopoietic cell transplantation (HCT) research community. This article
      summarizes issues to be considered in the use of PROs as endpoints in aGVHD
      prevention and treatment trials.

PMID- 19747557
TI  - Imaging cell signalling and movement in development.
AB  - Imaging is a method of choice to investigate the complex spatio-temporal cellular
      dynamics and the signalling pathways that control them during development. The
      ability to tag many proteins in vivo makes it possible to analyse the detailed
      dynamics of these interactions ranging over several orders of magnitude; from the
      study of single molecule events on the millisecond and nanometre scale up to the
      complex three-dimensional behaviour of cells in tissues on the millimetre scale
      over time periods of hours to days. Great advances are being made in the detailed
      study of molecular processes using high resolution imaging techniques in
      transparent samples close to the surface of cells or tissues, where light
      scattering is minimal. The major challenge is to translate some of these methods
      to the study of cells and tissues in their native 3D environment. These imaging
      methods require novel and innovative analysis methods to fully exploit the
      information available in these data. We will illustrate some of these points in
      the investigation of the development of the cellular slime mould Dictyostelium
      discoideum and the study of cell behaviours during gastrulation in the chick
      embryo.

PMID- 19747558
TI  - Systemic oxidative stress in patients with pulmonary sarcoidosis.
AB  - BACKGROUND: A local redox imbalance has been reported in pulmonary sarcoidosis.
      However, so far no study has described a systemic redox imbalance in this
      context. The aim of the present study was to evaluate the systemic oxidative
      stress in patients with sarcoidosis and determine its relationship to treatment
      and indices of disease severity. METHODS: 35 patients with histologically proven
      pulmonary sarcoidosis and 13 healthy volunteers were included in the study. All
      patients were studied during a stable phase of their disease. Systemic oxidative
      stress was quantified in serum with the use of a commercially available
      spectrophotometric method (D-ROM test) which determines overall oxidative stress,
      by measuring total hydroperoxides. Oxidative stress was expressed in conventional
      units, i.e. Carratelli Units (UCarr), where 1 UCarr corresponds to 0.8 mg/L
      H(2)O(2). RESULTS: Serum oxidative stress levels were significantly higher in
      patients with sarcoidosis compared to those of normal subjects (390+/-25 vs 300+/
      18 UCarr respectively, p=0.04). Patients not receiving systemic corticosteroids
      had higher levels of oxidative stress compared to steroid-treated patients
      (461.5+/-38 vs 315+/-20, p<0.01) and compared to controls (461.5+/-38 vs 300+/-18
      UCarr, p<0.01). Oxidative stress did not correlate with diffusion lung capacity
      (DLCO), partial arterial oxygen tension (PaO(2)), MRC dyspnoea scale or chest X
      ray stage. CONCLUSIONS: Systemic oxidative stress is increased in patients with
      stable pulmonary sarcoidosis who do not receive systemic corticosteroids. This
      finding suggests a sustained oxidative burden even when clinical, functional and
      radiological criteria indicate disease stability.

PMID- 19747559
TI  - Osmoregulatory traits of broad-toothed field mouse (Apodemus mystacinus)
      populations from different habitats.
AB  - One mechanism for physiological adjustment of small mammals to different habitats
      and different seasons is by seasonal acclimatization of their osmoregulatory
      system. We examined the abilities of broad-toothed field mice (Apodemus
      mystacinus) from different ecosystems ('sub-alpine' and 'Mediterranean') to cope
      with salinity stress under short day (SD) and long day (LD) photoperiod regimes.
      We compared urine volume, osmolarity, urea and electrolyte (sodium, potassium and
      chloride) concentrations. Significant differences were noted in the abilities of
      mice from the two ecosystems to deal with salinity load; in particular sub-alpine
      mice produced less concentrated urine than Mediterranean mice with SD- sub-alpine
      mice seeming to produce particularly dilute urine. Urea concentration generally
      decreased with increasing salinity, whereas sodium and potassium levels
      increased, however SD- sub-alpine mice behaved differently and appeared not to be
      able to excrete electrolytes as effectively as the other groups of mice.
      Differences observed provide an insight into the kinds of variability that are
      present within populations inhabiting different ecosystems, thus how populations
      may be able to respond to potential changes in their environment. Physiological
      data pertaining to adaptation to increased xeric conditions, as modelled by A.
      mystacinus, provides valuable information as to how other species may cope with
      potential climatic challenges.

PMID- 19747560
TI  - Stress-induced expression of protein disulfide isomerase associated 3 (PDIA3) in
      Atlantic salmon (Salmo salar L.).
AB  - In mammals, disulfide isomerase associated 3, PDIA3, is a member of the
      endoplasmic reticulum (ER) stress proteins, which can be induced by oxidative
      stress; however, its role in relation to stress regulation is still unknown in
      fish. Here, we report the cloning of a coding region of PDIA3 from the Atlantic
      salmon. PDIA3 mRNA expression was evaluated in the liver of Atlantic salmon
      exposed to environmental hyperoxia stress and toxic perfluorooctane sulfonate
      (PFOS) exposure stress. The PDIA3 sequence contained two PDI-typical thioredoxin
      active sites of WCGHC and shared approximately 70% identity with mammalian PDIA3,
      and its mRNA was primarily expressed in the liver. PDIA3 was significantly
      increased in the liver of Atlantic salmon exposed to hyperoxic water during
      smoltification. Also Mn superoxide dismutase (Mn-SOD) and CCAAT/enhancer binding
      protein (C/EBP), other markers of oxidative stress, were upregulated by
      hyperoxia. Furthermore, PFOS exposure of hepatocytes resulted in elevated mRNA
      expression of PDIA3, Mn-SOD and C/EBPdelta as well as peroxisome proliferator
      activated receptor gamma (PPARgamma). These results indicate a signaling
      connection between oxidative stress and ER stress. PDIA3 and C/EBPdelta may be
      valuable markers in fish for exposure and effect to environmental stress.

PMID- 19747561
TI  - Group I p21-activated kinases: emerging roles in immune function and viral
      pathogenesis.
AB  - Group I p21-activated kinases are a highly conserved three-member family of
      serine/threonine kinases that act as key effectors for the small GTPases Cdc42
      and Rac. In man, these enzymes have been implicated in a wide range of biological
      processes and are beginning to draw the attention of the pharmaceutical industry
      as potential therapeutic targets in cancer and in inflammatory processes. In this
      review, we summarize basic properties of group I Paks and discuss recently
      uncovered roles for these kinases in immune function and in viral infection.

PMID- 19747562
TI  - SOX-partner code for cell specification: Regulatory target selection and
      underlying molecular mechanisms.
AB  - Transcriptional regulatory functions of SOX proteins generally require the
      cooperation of partner factors that bind DNA in the vicinity of the SOX site.
      Each SOX-partner pair selects a specific group of regulatory target genes, with
      resultant gene expression patterns characterizing a particular cell
      differentiation state. Specific examples include the SOX2-OCT3/4 pairing in ES
      cells and the SOX2-PAX6 pairing in visual system primordia. When a component of a
      SOX-partner pair is exchanged with another factor, an overt transition of gene
      expression occurs in a cell, leading to the progression of developmental
      processes. When a SOX-partner protein pair activates its own genes, the global
      cell/tissue state is stabilized. Two major molecular mechanisms underlie SOX
      partner factor interactions: (1) cooperative DNA binding; and (2) protein
      interactions dependent upon DNA binding which elicit a large transactivation
      potential. In vivo evidence for and molecular mechanisms of the cell
      specification code attributed to the SOX-partner factor complexes are reviewed.

PMID- 19747563
TI  - JAK3: a two-faced player in hematological disorders.
AB  - JAK3 is a non-receptor tyrosine kinase, predominantly expressed in hematopoietic
      cells and that has been implicated in the signal transduction of the common gamma
      chain subfamily of cytokine receptors. As a result, JAK3 plays an essential role
      in hematopoieisis during T cell development. JAK3 inactivating mutations result
      in immunodeficiency syndromes (SCID) in both humans and mice. Recent data
      indicate that abnormal activation of JAK3 due to activating mutations is also
      found in human hematological malignancies, including acute megakaryoblastic
      leukemia (AMKL) and cutaneous T cell lymphoma (CTCL). After a brief summary of
      the JAK3 structure and function, we will review the evidence on the emerging role
      of JAK3 activation in hematological malignancies that warrant further studies to
      test the relevance of specific inhibition of JAK3 as a therapeutic approach to
      these challenging clinical entities.

PMID- 19747564
TI  - Individual domains of Tensin2 exhibit distinct subcellular localisations and
      migratory effects.
AB  - Tensins are large intracellular proteins believed to link the extracellular
      matrix to the cytoskeleton via integrins. Tensins are multidomain proteins
      consisting of homologous C1, PTPase, C2, SH2 and PTB domains. Full-length Tensin
      proteins can undergo cleavage inside cells, thus yielding domains in isolation
      that may have discrete subcellular localisations and downstream effects. We
      expressed different isoforms of Tensin2 and their individual domains as
      recombinant green fluorescent protein (GFP)-fusion constructs in DU145 human
      prostate cancer cells. Under fluorescence confocal microscopy, the isolated
      domains of Tensin2 all displayed discrete distributions throughout the cytoplasm
      and the nucleus. In particular, partial constructs containing the C1 domain
      localised preferentially to the nucleus, including the isolated C1 domain and the
      PTPase domain. In contrast, all three full-length isoforms of Tensin2 were
      present exclusively in discrete punctate bodies throughout the cytoplasm. This
      punctate staining showed colocalisation with the tumour suppressor protein DLC-1
      as well as with actin (phalloidin). Furthermore, DU145 cells transiently
      expressing partial Tensin2 constructs containing the PTB domain showed an
      increased haptotactic migration. In addition, stimulation of renal carcinoma
      cells stably expressing Tensin2 by the survival factor Gas6 caused
      phosphorylation of its receptor Axl, but no effect on Tensin2, which was already
      maximally phosphorylated at time 0. In conclusion, our results indicate that
      differential proteolytic cleavage of Tensin2 can liberate domains with discrete
      localisations and functions, which has implications for the role of Tensins in
      cancer cell survival and motility.

PMID- 19747565
TI  - Clara cell: progenitor for the bronchiolar epithelium.
AB  - Clara cells were first described as a morphologically distinct cell type by
      Kolliker in 1881, but they take their name from the seminal study of human and
      rabbit bronchioles by Max Clara in 1937. Since their discovery, Clara cells have
      been identified as central players in protecting the airway from environmental
      exposures. The diverse functions of Clara cells in lung homeostasis include roles
      in xenobiotic metabolism, immune system regulation, and progenitor cell activity.
      Recent identification of a sub-population of Clara cells as a bronchiolar tissue
      specific stem cell and a potential tumor initiating cell has focused the
      attention of cell and molecular biologists on the Clara cell and its behavior
      under normal and disease conditions.

PMID- 19747567
TI  - Moth olfactory trichoid sensilla exhibit nanoscale-level heterogeneity in surface
      lipid properties.
AB  - Chemical force microscopy (CFM) based on tapping mode Atomic force microscopy
      (AFM) utilized with topographic and phase-shift analyses was used to investigate
      the topography and surface chemical properties, respectively, of the long
      trichoid sensilla on the antennae of male Helicoverpa zea. AFM topographic
      imaging revealed regular series of step-ridges along nearly the entire length of
      each sensillum, except for the basal ca. 1/3 portions, which were devoid of such
      ridges. Inter-ridge regions were flat, with regularly spaced pores, ca. 30 nm in
      diameter populating these planar areas. Many pores exhibited a raised dome that
      often nearly completely spanned the depression, with only the edges of the
      depressed portion of the pore still visible. Some pores were observed also along
      the bases of the ridges. CFM probing of the surface for chemical interactions
      with the SiO(2) hydrophilic tip revealed consistently diminished hydrogen bonding
      of the ridge edge areas with the tip than along the flat planar inter-ridge
      regions. Surfaces of domes over the pores also tended to have less hydrogen
      bonding with the tip than the planar surfaces. Functionalizing the CFM tip by
      bonding octadecyl-hydrocarbon to it eliminated these surface chemical-CFM tip
      interactions and no differences in tip interaction with the sensillar surfaces
      were observed. Trichoid sensilla from the male antennae of a second species,
      Utethesia ornatrix, did not exhibit similar heterogeneity between ridge edges
      versus planar areas with regard to hydrogen bonding with the SiO(2) hydrophilic
      tip. Pores on U. ornatrix sensilla occurred only along the bases of ridges on
      their trichoid sensilla. We suggest that the surface lipids of the H. zea
      sensilla are distributed in a chemically heterogeneous fashion to aid adsorption
      and transport of aldehyde pheromone component molecules through the pores into
      the sensillum lumen, possibly through solubilization in an epicuticular lipid
      layer. The trichoid sensilla of U. ornatrix do not exhibit such surface chemical
      heterogeneity, and this species-difference may be due to the usage by U. ornatrix
      of hydrocarbon molecules rather than aldehydes for their sex pheromone
      components.

PMID- 19747566
TI  - Role of Wnt/beta-catenin signaling in liver metabolism and cancer.
AB  - Wnt/beta-catenin signaling is known for its role in embryogenesis as well as
      carcinogenesis. In the liver, it plays many critical roles during hepatic
      development and regeneration, and its dysregulation is evident in aberrant
      hepatic growth during various liver tumors. Its chief cellular roles in the liver
      include regulation of processes of cell proliferation, apoptosis, oxidative
      stress and differentiation, which in turn contributes to hepatic growth,
      zonation, xenobiotic metabolism and other metabolic processes inherent to the
      liver. Most of these functions of the Wnt/beta-catenin signaling are dictated
      through the highly temporal and tissue-specific or non-specific transcriptional
      targets of the pathway. In addition, some of the critical functions such as cell
      cell adhesion and perhaps maintenance of various junctions that are critical from
      an epithelial cell biology perspective are also a function of beta-catenin, which
      is the central component of the canonical Wnt pathway. Various animal models and
      clinical studies have demonstrated the spectra of Wnt/beta-catenin signaling in
      liver health and disease. Thus therapeutic modulation of this pathway for
      improved hepatic health is inevitable in the future. The current review discusses
      the advances in our understanding of the Wnt/beta-catenin signaling in liver
      physiology and pathology especially in hepatic metabolism and various tumors in
      adult liver and goes on to extrapolate the pre-clinical significance and possible
      translational implications of such findings.

PMID- 19747568
TI  - A thioredoxin response to the WSSV challenge on the Chinese white shrimp,
      Fenneropenaeus chinensis.
AB  - Thioredoxin (TRX) is involved in cell redox homeostasis. In addition, it is
      responsible for maintaining proteins in their reduced state. In our study, a
      Fenneropenaeus chinensis thioredoxin (FcTRX) gene was identified from the Chinese
      white shrimp. The full length of FcTRX was 777 bp, including a 60 bp 5'
      untranslated region (UTR), a 318 bp open reading frame (ORF) encoding a 105 amino
      acids protein, and a 399 bp 3' UTR. FcTRX contained a TRX domain with a conserved
      motif of Cys-Gly-Pro-Cys (CGPC). No signal peptide was predicted by SMART
      analysis. The molecular mass and pI of FcTRX were 12 kDa and 4.62, respectively.
      FcTRX is a widely distributed gene, and its mRNA is detected in hemocytes,
      hearts, hepatopancreas, gills, stomach, and intestine from an unchallenged
      shrimp. The expression level of FcTRX was the highest in hepatopancreas, where it
      was down-regulated to the lowest level at 12 h white spot syndrome virus (WSSV)
      challenge. In the gills, it went up to the highest level at 6 h. Western blot
      showed that FcTRX protein in hepatopancreas challenged with WSSV was down
      regulated from 2 h to 12 h and then restored to the level similar to that of
      unchallenged shrimp at 24 h. In the gills challenged with WSSV, the FcTRX protein
      was up-regulated from 6 h to 24 h. Our research indicated its possible role in
      the anti-WSSV innate immunity of shrimps.

PMID- 19747569
TI  - Complete amino acid sequence of three reptile lysozymes.
AB  - To study the structure and function of reptile lysozymes, we have reported their
      purification, and in this study we have established the amino acid sequence of
      three egg white lysozymes in soft-shelled turtle eggs (SSTL A and SSTL B from
      Trionyx sinensis, ASTL from Amyda cartilaginea) by using the rapid peptide
      mapping method. The established amino acid sequence of SSTL A, SSTL B, and ASTL
      showed substitutions of 43, 42, and 44 residues respectively when compared with
      the HEWL (hen egg white lysozyme) sequence. In these reptile lysozymes, SSTL A
      had one substitution compared with SSTL B (Gly126Asp) and had an N-terminal extra
      Gly and 11 substitutions compared with ASTL. SSTL B had an N-terminal extra Gly
      and 10 residues different from ASTL. The sequence of SSTL B was identical to soft
      shelled turtle lysozyme from STL (Trionyx sinensis japonicus). The Ile residue at
      position 93 of ASTL is the first report in all C-type lysozymes. Furthermore,
      amino acid substitutions (Phe34His, Arg45Tyr, Thr47Arg, and Arg114Tyr) were also
      found at subsites E and F when compared with HEWL. The time course using N
      acetylglucosamine pentamer as a substrate exhibited a reduction of the rate
      constant of glycosidic cleavage and increase of binding free energy for subsites
      E and F, which proved the contribution for amino acids mentioned above for
      substrate binding at subsites E and F. Interestingly, the variable binding free
      energy values occurred on ASTL, may be contributed from substitutions at outside
      of subsites E and F.

PMID- 19747570
TI  - Enhanced immunogenicity and cross-reactivity of HIV-1 V3-peptide and multiple
      antigen peptides conjugated to distinct carrier proteins.
AB  - To be effective, vaccines against the highly variable HIV-1 must elicit
      antibodies to a huge number of clinical isolates. For this purpose, new
      strategies to overcome this variability are needed. We previously reported a
      useful immunogenic strategy which consists of conjugating multiple antigen
      peptides (MAPs) to HBsAg. This vaccine candidate reduces the dose of immunogen
      required and increases the cross-reactivity towards other HIV strains. In the
      present study, we have expanded on those results by working with other carrier
      proteins. Thus, JY1-peptide (V3 regions of gp120 of HIV-1, subtype D) and JY1
      MAP8 were synthesized and coupled to several carrier proteins such as KLH, HBsAg
      and P64k (recombinant meningococcal protein). Mice were immunized with various
      conjugates and their antigenicity, immunogenicity, and the level of cross
      reactivity to a panel of five heterologous V3 peptides were compared. Our results
      show that conjugate JY1-MAP8 were not only more immunogenic than conjugate, they
      were also more or equally as immunogenic as 4-fold more JY1-MAP8 alone.
      Furthermore, conjugates to HBsAg and KLH were more immunogenic than those to
      P64k. Moreover, conjugates to HBsAg, KLH and P64k showed enhanced cross
      reactivity to heterologous V3 peptides compared to JY1-peptide and JY1-MAP8. The
      analysis showed that conjugate-based immunogens are more prompt to elicit
      immunogenicity and cross-reactivity. These results can find application in the
      development of HIV vaccine candidates.

PMID- 19747571
TI  - Risedronate prevents early radiation-induced osteoporosis in mice at multiple
      skeletal locations.
AB  - INTRODUCTION: Irradiation of normal, non-malignant bone during cancer therapy can
      lead to atrophy and increased risk of fracture at several skeletal sites,
      particularly the hip. This bone loss has been largely attributed to damaged
      osteoblasts. Little attention has been given to increased bone resorption as a
      contributor to radiation-induced osteoporosis. Our aims were to identify if
      radiation increases bone resorption resulting in acute bone loss and if bone loss
      could be prevented by administering risedronate. METHODS: Twenty-week-old female
      C57BL/6 mice were either: not irradiated and treated with placebo (NR+PL); whole
      body irradiated with 2 Gy x-rays and treated with placebo (IR+PL); or irradiated
      and treated with risedronate (IR+RIS; 30 microg/kg every other day). Calcein
      injections were administered 7 and 2 days before sacrifice. Bones were collected
      1, 2, and 3 weeks after exposure. MicroCT analysis was performed at 3 sites:
      proximal tibial metaphysis, distal femoral metaphysis, and the body of the 5th
      lumbar vertebra (L5). Osteoclasts were identified from TRAP-stained histological
      sections. Dynamic histomorphometry of cortical and trabecular bone was performed.
      Circulating TRAP5b and osteocalcin concentrations were quantified. RESULTS: In
      animals receiving IR+PL, significant (P<0.05) reduction in trabecular volume
      fraction relative to non-irradiated controls was observed at all three skeletal
      sites and time points. Likewise, radiation-induced loss of connectivity and
      trabecular number relative to NR+PL were observed at all skeletal sites
      throughout the study. Bone loss primarily occurred during the first week post
      exposure. Trabecular and endocortical bone formation was not reduced until week
      2. Loss of bone volume was absent in animals receiving IR+RIS. Histology
      indicated greater osteoclast numbers at week 1 within IR+PL mice. Serum TRAP5b
      concentration was increased in IR+PL mice only at week 1 compared to NR+PL
      (P=0.05). Risedronate treatment prevented the radiation-induced increase in
      osteoclast number, surface, and TRAP5b. CONCLUSIONS: This study demonstrated a
      rapid loss of trabecular bone at several skeletal sites after whole-body
      irradiation. Changes were accompanied by an increase in osteoclast number and
      serum markers of bone loss. Risedronate entirely prevented bone loss, providing
      further evidence that an increase in bone resorption likely caused this radiation
      induced bone loss.

PMID- 19747573
TI  - Non-enzymatic glycation alters microdamage formation in human cancellous bone.
AB  - INTRODUCTION: The accumulation of advanced glycation end-products (AGEs) in bone
      has been suggested to adversely affect the fracture resistance of bone with
      aging, diabetes, and pharmacological treatments. The formation of AGEs increases
      crosslinking in the organic matrix of bone but it is unknown how elevated levels
      of AGEs affect the mechanisms of fracture resistance such as microdamage
      formation. METHODS: Human tibial cancellous bone cores were subjected to non
      enzymatic glycation (NEG) by in vitro ribosylation and were mechanically loaded
      to pre- (0.6%) and post- (1.1%) yield apparent level strains. Loaded specimens
      were stained with lead-uranyl acetate and subjected to microCT-based 3D
      quantification and characterization of microdamage as either diffuse damage and
      linear microcracks. Damaged volume per bone volume (DV/BV) and damaged surface
      per damaged volume (DS/DV) ratios were used to quantify the volume and morphology
      of the detected microdamage, respectively. RESULTS: In vitro ribosylation
      increased the microdamage morphology parameter (DS/DV) under both pre- (p<0.05;
      +51%) and post-yield loading (p<0.001; +38%), indicating that the alteration of
      bone matrix by NEG caused the formation of crack-like microdamage morphologies.
      Under post-yield loading, the NEG-mediated increase in DS/DV was coupled with the
      reductions in microdamage formation (DV/BV; p<0.001) and toughness (p<0.001).
      DISCUSSION: Using a novel microCT technique to characterize and quantify
      microdamage, this study shows that the accumulation of AGEs in the bone matrix
      significantly alters the quantity and morphology of microdamage production and
      results in reduced fracture resistance.

PMID- 19747574
TI  - Collection of routine national seasonal influenza vaccine coverage data from GP
      practices in England using a web-based collection system.
AB  - This paper describes a web-based system developed to collect data on influenza
      (flu) vaccine uptake in near real time during the flu season in England. Data are
      collected from all GP practices providing the immunisation programme. Data are
      submitted either monthly or weekly on-line to a website using manual, automated
      and semi-automated methods. During the 2008/09 season, a final response rate of
      96.2% was achieved (n=7980/8293). This equates to 52,217,430 GP registered
      patients aged 6 months and over being included in the survey. The majority of
      reports (65.5%) were submitted via automated or semi-automated methods. We were
      also able to collect the data weekly from a sentinel group of GP practices
      (approximately 50%) that have fully automated data extraction facilities. This
      system successfully provides data locally and nationally to monitor the annual
      seasonal flu programme, with a large sample size, quickly and efficiently, with
      minimal burden on the NHS. At a time when the first influenza pandemic of the
      21st century is occurring, the ability to measure influenza vaccine uptake
      coverage in near real time will be invaluable.

PMID- 19747572
TI  - Hormone predictors of abnormal bone microarchitecture in women with anorexia
      nervosa.
AB  - Osteopenia is a complication of anorexia nervosa (AN) associated with a two- to
      three-fold increase in fractures. Nutritional deficits and hormonal abnormalities
      are thought to mediate AN-induced bone loss. Alterations in bone
      microarchitecture may explain fracture risk independent of bone mineral density
      (BMD). Advances in CT imaging now allow for noninvasive evaluation of trabecular
      microstructure at peripheral sites in vivo. Few data are available regarding bone
      microarchitecture in AN. We therefore performed a cross-sectional study of 23
      women (12 with AN and 11 healthy controls) to determine hormonal predictors of
      trabecular bone microarchitecture. Outcome measures included bone
      microarchitectural parameters at the ultradistal radius by flat-panel volume CT
      (fpVCT); BMD at the PA and lateral spine, total hip, femoral neck, and
      ultradistal radius by dual energy X-ray absorptiometry (DXA); and IGF-I, leptin,
      estradiol, testosterone, and free testosterone levels. Bone microarchitectural
      measures, including apparent (app.) bone volume fraction, app. trabecular
      thickness, and app. trabecular number, were reduced (p<0.03) and app. trabecular
      spacing was increased (p=0.02) in AN versus controls. Decreased structural
      integrity at the ultradistal radius was associated with decreased BMD at all
      sites (p<or=0.05) except for total hip. IGF-I, leptin, testosterone, and free
      testosterone levels predicted bone microarchitecture. All associations between
      both IGF-I and leptin levels and bone microarchitectural parameters and most
      associations between androgen levels and microarchitecture remained significant
      after controlling for body mass index. We concluded that bone microarchitecture
      is abnormal in women with AN. Endogenous IGF-I, leptin, and androgen levels
      predict bone microarchitecture independent of BMI.

PMID- 19747575
TI  - Development of duck hepatitis A virus type 3 vaccine and its use to protect
      ducklings against infections.
AB  - A variant type of duck hepatitis A virus (DHAV), DHAV-3 was recently discovered
      in South Korea and China. Sequence analyses verified that the variant is
      genetically or serologically different from the DHAV-1 and DHAV-2 types. Duck
      hepatitis had been reported in South Korea since 1985 and an attenuated DHAV-1
      vaccine had efficiently prevented epidemics of DHAV-1 until 2002. Despite the
      DHAV-1 based vaccine in use the novel DHAV-3 circulating in South Korea remains
      to be a threat to duckling farming. To develop a live attenuated vaccine against
      DHAV-3, a representative isolate, AP-04203, was therefore attenuated by repeated
      passages in SPF chicken embryos 100 times. The 100th passaged virus, AP
      04203P100, did not cause clinical sign and mortality in 1-day-old ducklings as
      well as reversion of virulence capacity. The ducklings vaccinated with AP
      04203P100 virus (10(3.0)ELD(50)/0.2ml) on 1-day-old age via the intramuscular
      injection were well protected from 2 days after challenge with pathogenic
      AP04203P1 virus via the intramuscular route. In addition, the vaccine candidate
      also exhibited complete protection against currently circulating pathogenic DHAV
      3 isolates. In conclusion, we demonstrate that the live attenuated virus, AP
      04203P100, is a promising vaccine candidate facilitating the prevention of duck
      hepatitis caused by DHAV-3 around East Asia including South Korea.

PMID- 19747576
TI  - Functional properties and epitope characteristics of T-cells recognizing natural
      HIV-1 variants.
AB  - To understand how broad recognition of HIV-1 variants may be achieved we examined
      T-cell reactivity in newly infected persons as well as vaccine recipients to a
      broad spectrum of potential T-cell epitope (PTE) variants containing
      conservative, semi-conservative and non-conservative amino acid substitutions.
      Among early infected persons T-cells recognized epitope variants with one
      substitution at a significantly higher frequency versus those with two (P=0.0098)
      and three (P=0.0125) substitutions. Furthermore T-cells recognized variants
      containing conservative substitutions at a higher frequency versus those
      containing semi-conservative (P=0.0029) and non-conservative (P<0.0001)
      substitutions. Similar effects were observed on recognition of variants by
      vaccine-induced T-cells. Moreover even when variants were recognized, the IFN
      gamma and granzyme B responses as well as T-cell proliferation were of lower
      magnitude. Finally, we show that epitope distribution is strongly influenced by
      both processing preferences and amino acid entropy. We conclude that induction of
      broad immunity is likely to require immunogen sequences that encompass multiple
      variants. However, cost-effective design of peptide and sequence based vaccine
      immunogens that provide maximal coverage of circulating sequences may be achieved
      through emphasis on virus domains likely to be T-cell targets.

PMID- 19747577
TI  - Risk of lymphoma and leukaemia after bacille Calmette-Guerin and smallpox
      vaccination: a Danish case-cohort study.
AB  - Vaccines may have non-specific effects as suggested mainly in mortality studies
      from low-income countries. The objective was to examine the effects of BCG and
      smallpox vaccinations on subsequent risk of lymphoma and leukaemia in a Danish
      population experiencing rapid out-phasing of these vaccines. In a background
      cohort (N=47,622) from the Copenhagen School Health Records Register, cases of
      leukaemia (N=20) and lymphoma (N=51) were identified through the Danish Cancer
      Registry. The vaccination status of the cases was compared with the vaccination
      status of a 5% random sample (N=2073) of the background cohort and analysed in a
      case-cohort design. BCG vaccination reduced the risk of lymphomas (HR=0.49 (95%
      CI: 0.26-0.93)), whereas smallpox vaccination did not (HR=1.32 (0.56-3.08)). With
      the small number of leukaemia cases, the analysis of leukaemia had limited power
      (BCG vaccination HR=0.81 (0.31-2.16); smallpox vaccination HR=1.32 (0.49-3.53)).
      The present study with very reliable vaccine history information indicates a
      beneficial effect of BCG vaccination on the risk of lymphomas.

PMID- 19747578
TI  - First data on Eurasian wild boar response to oral immunization with BCG and
      challenge with a Mycobacterium bovis field strain.
AB  - The Eurasian wild boar (Sus scrofa) is considered a reservoir for bovine
      tuberculosis (bTB) caused by Mycobacterium bovis and closely related members of
      the Mycobacterium tuberculosis complex in south-central Spain. The vaccination of
      wildlife with BCG offers an alternative to culling and to movement restriction
      for the control of bTB among wildlife reservoirs. In this study, we hypothesized
      that oral BCG immunization of wild boar would affect the expression of
      immunoregulatory genes and confer protection against M. bovis. Three groups were
      used to describe the infection, pathological findings and gene expression
      profiles in wild boar: BCG-vaccinated and M. bovis-challenged (vaccinated
      challenged group; N=6), non-vaccinated and M. bovis-challenged (non-vaccinated
      challenged group; N=4), and non-vaccinated and mock-infected (control group; N=2)
      animals. M. bovis was isolated from 50% (3/6) and 75% (3/4) of vaccinated
      challenged and non-vaccinated challenged animals, respectively. All four wild
      boar from the non-vaccinated challenged group developed bTB-compatible lesions
      114 days after challenge. In contrast, only 50% of vaccinated challenged wild
      boar developed lesions. The PBMC mRNA levels of IL4, RANTES, C3, IFN-gamma and
      methylmalonyl-CoA mutase (MUT) were analyzed at several days post-vaccination
      (dpi). When vaccinated challenged animals were compared to controls, all five
      genes were significantly upregulated at the time of M. bovis infection at 186dpi
      but IFN-gamma levels were also upregulated at 11 and 46dpi. The C3 and MUT mRNA
      levels were higher at 46dpi, and 11 and 186dpi, respectively, in vaccinated
      protected wild boar when compared to non-vaccinated challenged animals. At the
      end of the experiment (300dpi), the mRNA levels of selected genes were lower in
      non-vaccinated challenged animals when compared to control wild boar. Exposing
      wild boar to a dose of 10(4)cfu of M. bovis by the oropharyngeal route is an
      adequate protocol to produce an infection model in this species. Our results
      suggested that oral BCG immunization of wild boar results in the upregulation of
      immunoregulatory genes that may be associated with protective response to M.
      bovis infection in this species. More studies on vaccine efficacy, delivery, and
      safety will be needed to confirm if oral vaccination with BCG could be used in
      bTB control programs for reducing M. bovis infection and clinical disease in wild
      boar.

PMID- 19747579
TI  - Development of candidate combination vaccine for hepatitis E and hepatitis B: a
      liposome encapsulation approach.
AB  - To reduce extra injections, cost and ensure better coverage, use of combination
      vaccines is preferable. An attempt was made to evaluate the encapsulation of
      hepatitis E virus neutralizing epitope (NE) region and hepatitis B virus surface
      antigen (HBsAg) in liposomes as DNAs, proteins and DNA+protein. Mice groups were
      immunized with different liposome-encapsulated formulations and monitored for
      anti-HEV and anti-HBs titres, IgG subtypes, antigen-specific lymphocyte
      proliferation and cytokine levels. The protective levels of anti-HBs and in vitro
      virus-binding capacity of anti-HEV antibodies were assessed. Liposome
      encapsulated DNA either singly or in combination did not elicit antibody
      response. Anti-HEV and anti-HBs IgG titres of individual component of protein
      alone (Lipo-E-P/Lipo-B-P) or DNA+protein formulations (Lipo-E-DP/Lipo-B-DP) were
      comparable to respective titres in combination vaccine of protein (Lipo-BE-P) and
      DNA+protein formulations (Lipo-BE-DP). IgG1 levels were significantly higher in
      Lipo-BE-P group whereas, equivalent levels of IgG1 and IgG2a were observed in
      Lipo-BE-DP group against both components of the vaccine. Combination vaccine
      group showed mixed Th1/Th2 cytokine profile. Liposome entrapped NE and HBsAg in
      protein and DNA+protein formats induce excellent immune response to both the
      components and need to be evaluated in higher animals.

PMID- 19747580
TI  - Another step towards the understanding of the earliest stages of osteoarthritis.

PMID- 19747581
TI  - The effect of oral salmon calcitonin delivered with 5-CNAC on bone and cartilage
      degradation in osteoarthritic patients: a 14-day randomized study.
AB  - BACKGROUND: The aim of this study was to investigate the pharmacokinetic and
      pharmacodynamic parameters of oral salmon calcitonin (oSCT) administered over 14
      days to men and women presenting with osteoarthritis (OA). MATERIALS AND METHODS:
      The study was a phase-I, 2-week, placebo-controlled, double-blind, double-dummy,
      randomized, gender-stratified study including 73 subjects aged 57-75 years.
      Patients had painful OA with a Kellgren and Lawrence index score of I-III.
      Treatment allocations were; 0.6 mg, 0.8 mg of oSCT, or placebo. Treatment was
      given twice daily for 14 days. The morning dose was administered between 07:00
      and 08:00 at least 30 min before breakfast. The second dose was administered 30
      min before evening dinner. On treatment day 1 and 14, the morning dose was
      followed by 5h of fasting, and blood samples and urine were collected immediately
      prior to dosing and according to the protocol. Study parameters were: plasma sCT
      levels, bone resorption by CTX-I (serum C-terminal telopeptide of collagen type
      I), bone formation by osteocalcin (serum OC), and cartilage degradation by CTX-II
      (urine C-terminal telopeptide of collagen type II) (clinicaltrials.gov
      identifier: NCT00486369). RESULTS: Doses of 0.8 mg compared with 0.6 mg produced
      significantly higher C(max) and AUC(0-4 hrs), of calcitonin, P=0.03. This
      resulted in significant reductions in CTX-I and CTX-II, [P<0.0001; P=0.007]. No
      differences were observed between baseline and follow-up at day 14 in
      pharmacokinetic and pharmacodynamic parameters. Gender had no observable
      influence on results. CONCLUSIONS: oSCT given twice daily with a pre-dinner and
      morning fasting dosing resulted in reductions in markers of bone resorption and
      cartilage degradation.

PMID- 19747582
TI  - Radiological joint space width in the clinically normal hips of a Korean
      population.
AB  - OBJECTIVE: The purpose of this paper was to investigate the association of the
      joint space width (JSW) of the hip with radiologically observed hip deformity,
      the anthropological features and aging in a clinically asymptomatic Korean
      population. DESIGN: 428 consecutive patients who were without clinical evidence
      of hip osteoarthritis (OA) and who underwent supine anteroposterior (AP) pelvic
      radiography for hip contusion or a routine health check were analyzed for the
      relation of joint space narrowing to the center-edge (CE) angle, the acetabular
      depth, the head-neck ratio, the neck-shaft angle, the pelvic width, the height,
      the body mass index (BMI), gender and age. RESULTS: The CE angle was inversely
      associated with the superomedial JSW and the superolateral JSW. The acetabular
      depth was positively associated with superomedial JSW. A decreased head-neck
      ratio and the neck-shaft angle were not associated with the superomedial or
      superolateral JSW. The height was positively associated with an increased
      superomedial JSW, but not with the superolateral JSW. The BMI and increased age
      were positively associated with the superolateral JSW, but not with the
      superomedial JSW. CONCLUSION: Our study showed that the CE angle was the single
      constant radiological parameter that was inversely related to the JSW of hip
      joints. Further, the height was positively related to the superomedial JSW while
      the BMI was positively related to the superolateral JSW. The normal aging process
      was not associated with joint space narrowing of the hip joint.

PMID- 19747583
TI  - Elevated osteopontin level of synovial fluid and articular cartilage is
      associated with disease severity in knee osteoarthritis patients.
AB  - OBJECTIVE: To investigate osteopontin (OPN) levels in both synovial fluid and
      articular cartilage of patients with primary knee osteoarthritis (OA) and their
      relationship with severity of the disease. METHOD: Fifty patients aged 48-81
      years with knee OA and 10 healthy controls were enrolled in this study.
      Anteroposterior knee radiographs or/and Mankin score were taken to determine the
      disease severity of the affected knee. The radiographic grading of OA in the knee
      was performed by using the Kellgren-Lawrence criteria. OPN levels in synovial
      fluid were measured using enzyme-linked immunosorbent assay. OPN levels in
      articular cartilage were assessed by immunohistochemical methods. RESULTS:
      Compared to healthy controls, OA patients had higher OPN concentration in
      synovial fluid (4519.60+/-1830.37, 95%CI 3999.42-5039.79 vs 1179.70+/-303.39,
      95%CI 1035.53-1438.74 pg/ml, P<0.001)and articular cartilage(0.6+/-0.06, 95%CI
      0.59-0.62 vs 0.43+/-0.07, 95%CI 0.38-0.48, P<0.01). In addition, synovial fluid
      OPN levels showed a positive correlation with articular cartilage OPN levels
      (r=0.411, 95%CI 0.150-0.619, P=0.003). Subsequent analysis showed that synovial
      fluid OPN levels significantly correlated with severity of disease (Spearman's
      rho=0.581, 95%CI 0.335-0.726, P<0.001). Furthermore, the articular cartilage
      levels of OPN also correlated with disease severity (Spearman's rho=0.675, 95%CI
      0.500-0.808, P<0.001). CONCLUSIONS: OPN in synovial fluid and articular cartilage
      is associated with progressive joint damage and is likely to be a useful
      biomarker for determining disease severity and progression in knee OA.

PMID- 19747584
TI  - Evaluation of histological scoring systems for tissue-engineered, repaired and
      osteoarthritic cartilage.
AB  - OBJECTIVE: Regeneration of hyaline cartilage has been the focus of an increasing
      number of research groups around the world. One of the most important outcome
      measures in evaluation of its success is the histological quality of
      cartilaginous tissue. Currently, a variety of histological scoring systems is
      used to describe the quality of osteoarthritic, in vivo repaired or in vitro
      engineered tissue. This review aims to provide an overview of past and currently
      used histological scoring systems, in an effort to aid cartilage researchers in
      choosing adequate and validated cartilage histological scoring systems. METHODS:
      Histological scoring systems for analysis of osteoarthritic, tissue engineered
      and in vivo repaired cartilage were reviewed. The chronological development as
      well as the validity and practical applicability of the scoring systems is
      evaluated. RESULTS: The Histological-Histochemical Grading System (HHGS) or a
      HHGS-related score is most often used for evaluation of osteoarthritic cartilage,
      however the Osteoarthritis Research Society International (OARSI) Osteoarthritis
      Cartilage Histopathology Assessment System seems a valid alternative. The
      O'Driscoll score and the International Cartilage Repair Society (ICRS) II score
      may be used for in vivo repaired cartilage. The 'Bern score' seems most adequate
      for evaluation of in vitro engineered cartilage. CONCLUSION: A great variety of
      histological scoring systems exists for analysis of osteoarthritic or normal, in
      vivo repaired or tissue-engineered cartilage, but only few have been validated.
      Use of these validated scores may considerably improve exchange of information
      necessary for advances in the field of cartilage regeneration.

PMID- 19747585
TI  - Vibration training intervention to maintain cartilage thickness and serum
      concentrations of cartilage oligometric matrix protein (COMP) during
      immobilization.
AB  - OBJECTIVE: To test the hypotheses that 1) 14-days of immobilization of young
      healthy subjects using a 6 degrees -"head-down-tilt-bed-rest"-model (6 degrees 
      HDT) would reduce cartilage thickness in the knee and serum Cartilage oligometric
      matrix protein (COMP) concentration and 2) isolated whole body vibration training
      would counteract the bed rest effects. METHOD: The study was performed and
      designed in compliance with the Declaration of Helsinki and is registered as
      trial DRKS00000140 in the German Clinical Trial Register (register.germanctr.de).
      Eight male healthy subjects (78.0+/-9.5kg; 179+/-0.96cm, 26+/-5 years) performed
      14 days of 6 degrees -HDT. The study was designed as a cross-over-design with two
      study phases: a training and a control intervention. During the training
      intervention, subjects underwent 2x5-min whole body vibration training/day
      (Frequency: 20Hz; amplitude: 2-4mm). Magnetic resonance (MR) images (slice
      thickness: 2mm; in-plane resolution: 0.35x0.35mm; pixels: 448x512) were taken
      before and after the 6 degrees -HDT periods. Average cartilage thicknesses were
      calculated for the load bearing regions on the medial and lateral articulating
      surfaces in the femur and tibia. RESULTS: While the control intervention resulted
      in an overall loss in average cartilage thickness of -8% (pre: 3.08mm+/-0.6mm
      post: 2.82mm+/-0.6mm) in the weight-bearing regions of the tibia, average
      cartilage thickness increased by 21.9% (pre: 2.66mm+/-0.45mm post: 3.24mm+/
      0.63mm) with the vibration intervention. No significant differences were found in
      the weight-bearing regions of the femur. During both interventions, reduced serum
      COMP concentrations were observed (control intervention: -13.6+/-8.4%; vibration
      intervention: -9.9+/-3.3%). CONCLUSION: The results of this study suggest that
      articular cartilage thickness is sensitive to unloading and that vibration
      training may be a potent countermeasure against these effects. The sensitivity of
      cartilage to physical training is of high relevance for training methods in space
      flight, elite and sport and rehabilitation after illness or injury.

PMID- 19747587
TI  - Signal transduction and metabolism in chondrocytes is modulated by lactoferrin.
AB  - OBJECTIVE: Activation of granulocytes causes a considerable rise in the
      concentration of lactoferrin (Lf) in synovial fluid (SF). We here investigate
      consequences thereof on signal transduction and the balance between catabolic and
      anabolic metabolism in chondrocytes. METHODS: Signal transduction was analysed in
      cultured chondrocytes by immunodetection of mitogen activated protein kinases
      (MAPK) and analysis of Smad2 translocation to the nucleus. Expression levels of
      matrix metalloproteinases (MMPs) and of aggrecan were measured by reverse
      transcription-PCR. The proteolytic activity of MMPs was ascertained by
      zymography. Expression of the low-density-lipoprotein-receptor-related-protein-1
      (LRP-1), a Lf receptor for signalling, was assayed by immunohistochemistry in
      cartilage and in cultured chondrocytes by immunoblotting. RESULTS: We found LRP-1
      expressed in dedifferentiated chondrocytes in culture and in cartilage tissue
      preferentially on the articular surface where it can encounter Lf within SF. Lf
      stimulated proliferation of chondrocytes, comparable to transforming growth
      factor-beta1 (TGFbeta1) and activated p38 and the extracellular-signal regulated
      kinases 1/2 (ERK1/2) within minutes. Surprisingly, Lf induced nuclear Smad2
      translocation, a signal pathway ascribed to TGFbeta receptor activation. Lf
      significantly increased the levels of catabolic indicators such as MMP1, MMP2,
      MMP3 and MMP13 and inhibited aggrecan synthesis. CONCLUSION: Lf is a robust
      regulator of chondrocyte metabolism, comparable to TGFbeta1. The catabolic
      influence together with the proliferative stimulus indicates a function as an
      early phase cytokine, enhancing MMPs, necessary for degradation of damaged tissue
      and stimulating proliferation of chondrocytes, necessary for reconstruction.

PMID- 19747586
TI  - Mechanical load inhibits IL-1 induced matrix degradation in articular cartilage.
AB  - OBJECTIVE: Osteoarthritis is a disease process of cellular degradation of
      articular cartilage caused by mechanical loads and inflammatory cytokines. We
      studied the cellular response in native cartilage subjected to a mechanical load
      administered simultaneously with an inflammatory cytokine interleukin-1 (IL-1),
      hypothesizing that the combination of load and cytokine would result in
      accelerated extracellular matrix (ECM) degradation. METHODS: Mature bovine
      articular cartilage was loaded for 3 days (stimulation) with 0.2 and 0.5 MPa
      stresses, with and without IL-1 (IL-1alpha, 10 ng/ml), followed by 3 days of no
      stimulation (recovery). Aggrecan and collagen loss were measured as well as
      aggrecan cleavage using monoclonal antibodies AF-28 and BC-3 for cleavage by
      aggrecanases (ADAMTS) and matrix metalloproteinases (MMPs), respectively.
      RESULTS: Incubation with IL-1 caused aggrecan cleavage by aggrecanases and MMPs
      during the 3 days of stimulation. A load of 0.5 MPa inhibited the IL-1-induced
      aggrecan loss while no inhibition was found for the 0.2 MPa stress. There was no
      collagen loss during the treatments but upon load and IL-1 removal proteoglycan
      and collagen loss increased. Load itself under these conditions was found to have
      no effect when compared to the unloaded controls. CONCLUSIONS: A mechanical load
      of sufficient magnitude can inhibit ECM degradation by chondrocytes when
      stimulated by IL-1. The molecular mechanisms involved in this process are not
      clear but probably involve altered mechanochemical signal transduction between
      the ECM and chondrocyte.

PMID- 19747589
TI  - [Editorial].

PMID- 19747590
TI  - The silent epidemic of neurodevelopmental injuries.

PMID- 19747592
TI  - Reprint of "Dynamics of the expression of intermediate filaments vimentin and
      desmin during myofibroblast differentiation after corneal injury".
AB  - Previous studies have suggested that abnormal corneal wound healing in patients
      after photorefractive keratectomy (PRK) is associated with the appearance of
      myofibroblasts in the stroma between two and four weeks after surgery. The
      purpose of this study was to examine potential myofibroblast progenitor cells
      that might express other filament markers prior to completion of the
      differentiation pathway that yields alpha-smooth muscle actin (SMA)-expressing
      myofibroblasts associated with haze localized beneath the epithelial basement
      membrane after PRK. Twenty-four female rabbits that had -9 diopter PRK were
      sacrificed at 1 week, 2 weeks, 3 weeks or 4 weeks after surgery. Corneal rims
      were collected, frozen at -80 degrees C, and analyzed by immunocytochemistry
      using anti-vimentin, anti-desmin, and anti-SMA antibodies. Double immunostaining
      was performed for the co-localization of SMA with vimentin or desmin with SMA. An
      increase in vimentin expression in stromal cells is noted as early as 1 week
      after PRK in the rabbit cornea. As the healing response continues at two or three
      weeks after surgery, many stromal cells expressing vimentin also begin to express
      desmin and SMA. By 4 weeks after the surgery most, if not all, myofibroblasts
      express vimentin, desmin and SMA. Generalized least squares regression analysis
      showed that there was strong evidence that each of the marker groups differed in
      expression over time compared to the other two (p<0.01). Intermediate filaments-
      vimentin and desmin co-exist in myofibroblasts along with SMA and may play an
      important role in corneal remodeling after photorefractive keratectomy. The
      earliest precursors of myofibroblasts destined to express SMA and desmin are
      detectable by staining for vimentin at 1 week after surgery.

PMID- 19747593
TI  - [Repeated thrombolysis with tenecteplase as a bridge to valvular replacement in a
      case of preoclusive mitral prosthetic thrombosis].

PMID- 19747594
TI  - Top-down modulation of prepulse inhibition of the startle reflex in humans and
      rats.
AB  - Prepulse inhibition (PPI) is the attenuation of the startle reflex when the
      sudden intense startling stimulus is shortly preceded by a weaker, non-startling
      sensory stimulus (prepulse). PPI reflects a protective function of reducing
      disruptive influences to the processing of prepulse signals and is recognized as
      a model of sensorimotor gating. In humans, PPI is modulated by both attentional
      and emotional responses to prepulse, indicating that this early-stage gating is
      top-down modulated by higher-order cognitive processes. Recent studies have
      confirmed top-down modulation of PPI in animals, because PPI in rats is enhanced
      by auditory fear conditioning and perceived separation between fear-conditioned
      prepulse and masker. This review summarizes recent studies of top-down modulation
      of PPI conducted in humans and those in rats. Since both baseline PPI and
      attentional modulation of PPI in patients with schizophrenia are impaired, and
      both baseline PPI and conditional modulation of PPI in rats with isolation
      rearing are impaired, this review emphasizes that investigation of top-down
      modulation of PPI is critical for establishing new animal models for studying
      both cognitive features and neural bases of schizophrenia. Deficits in either
      baseline PPI or attentional modulation of PPI in either patients with attention
      deficit/hyperactivity disorder (ADHD) or ADHD-modeling rats are also discussed.

PMID- 19747595
TI  - Executive control in language processing.
AB  - During communication, speakers and listeners need the mechanisms of executive
      control to organize thoughts and actions along internal goals. Speakers may use
      executive functions to select the right word over competing alternatives to refer
      to the concept in mind. Listeners may use executive functions to coordinate the
      outputs of multiple linguistic processes to reach a coherent interpretation of
      what others say. Bilinguals may use executive functions to control which language
      is to use or to switch from one language to another. The control mechanisms
      recruited in language processing may be similar to those recruited in perception
      and attention, supported by a network of frontal, parietal and sub-cortical brain
      structures. Here we review existing evidences regarding the involvement of domain
      general executive control in language processing. We will explain how executive
      functions are employed to control interference in comprehension and production,
      within and across languages.

PMID- 19747596
TI  - Roles of calcitonin gene-related peptide and its receptors in pain-related
      behavioral responses in the central nervous system.
AB  - Calcitonin gene-related peptide (CGRP) is a 37 amino-acid peptide, which is
      widely distributed in peripheral and central nervous system. There are two types
      of CGRP receptors, CGRP receptor 1 and CGRP receptor 2. It is known that CGRP
      plays important roles in multiple physiological processes. Studies demonstrate
      that CGRP and CGRP receptors are involved in the transmission and modulation of
      pain information in peripheral and central nervous system. CGRP8-37, a specific
      antagonist for CGRP receptor 1, is widely used to differentiate the two typical
      CGRP receptors. There are two ambiguous points about the effects of CGRP and
      CGRP8-37 on pain-related behavioral responses. The first is the effects of
      exogenous CGRP and CGRP8-37 on the transmission and regulation of pain
      information in the spinal cord. The second is the effects of these peptides in
      pain modulation at super-spinal levels. The specific goal of this review is to
      summarize the roles of CGRP, CGRP8-37 and CGRP receptors in pain-related
      behavioral responses in the central nervous system.

PMID- 19747597
TI  - Receptor trafficking induced by mu-opioid-receptor phosphorylation.
AB  - Opiates, including morphine, are widely used drugs for antinociception in
      clinics. Prolonged treatments of opioids induce both tolerance and dependence,
      which are the major side effects of opioid therapy. One of the mechanisms for the
      development of tolerance and dependence is implicated to be opioid-receptor
      trafficking. Here we review the current understandings of opioid-receptor
      phosphorylation, endocytosis and desensitization after repeated agonist
      treatments. Also, the role of G-protein coupled receptor kinases in opioid
      receptor phosphorylation is discussed. How to associate these observations to
      physiological and behavioral changes in animal models and clinics is still under
      investigation.

PMID- 19747598
TI  - Bread is an essential part of human nutrition and culture. Editorial.

PMID- 19747599
TI  - Biodiversity, ecological determinants, and metabolic exploitation of sourdough
      microbiota.
AB  - Sourdough is a microbial ecosystem of lactic acid bacteria (LAB) and yeasts in a
      matrix of mainly cereal flour and water. Culture-dependent and culture
      independent microbiological analysis together with metabolite target analyses of
      different sourdoughs enabled to understand this complex fermentation process. It
      is difficult to link the species diversity of the sourdough microbiota with the
      (geographical) type of sourdough and the flour used, although the type and
      quality of the latter is the main source of autochthonous LAB in spontaneous
      sourdough fermentations and plays a key role in establishing stable microbial
      consortia within a short time. Carbohydrate fermentation targeted towards maltose
      catabolism, the use of external alternative electron acceptors, amino acid
      transamination reactions, and/or the arginine deiminase pathway are metabolic
      activities that favour energy production, cofactor (re)cycling, and/or tolerance
      towards acid stress, and hence contribute to the competitiveness and dominance of
      certain species of LAB found in sourdoughs. Also, microbial interactions play an
      important role. The availability of genome sequences for several LAB species that
      are of importance in sourdough as well as technological advances in the fields of
      functional genomics, transcriptomics, and proteomics enable new approaches to
      study sourdough fermentations beyond the single species level and will allow an
      integral analysis of the metabolic activities and interactions taking place in
      sourdough. Finally, the implementation of selected starter cultures in sourdough
      technology is of pivotal importance for the industrial production of sourdoughs
      to be used as flavour carrier, texture-improving, or health-promoting dough
      ingredient.

PMID- 19747600
TI  - Sourdough in gluten-free bread-making: an ancient technology to solve a novel
      issue?
AB  - The increasing demand for high quality gluten-free (GF) bread, clean labels and
      natural products is raising the need for new approaches in GF bread-making.
      Sourdough is the foremost fermentation used for baking purposes and it has been
      proven to be ideal for improving the texture, palatability, aroma, shelf life and
      nutritional value of wheat and rye breads. These characteristic features derive
      from the complex metabolic activities of the sourdough-resident lactic acid
      bacteria and yeasts, e.g. acidification, production of exopolysaccharides,
      proteolytic- amylolytic- and phytase activity, and production of antimicrobial
      substances. These effects have been extensively studied and well described for
      traditional baking, whereas little is known about the role of sourdough in GF
      baking. Yet, the microbiological and qualitative characterisation of local GF
      fermented products indicate an overlap with the microbiota of wheat/rye
      fermentation and suggest that the positive metabolic activities of the sourdough
      microbiota are still retained during fermentation of GF crops. Thus, the use of
      sourdough in GF baking may be the new frontier for improving the quality, safety
      and acceptability of GF bread.

PMID- 19747601
TI  - Rich nutrition from the poorest - cereal fermentations in Africa and Asia.
AB  - Cereal fermentations in Africa and Asia involve mainly the processing of maize,
      rice, sorghum and the millets. Lactic acid bacteria (Lactobacillus, Pediococcus),
      Enterobacter spp., yeasts (Candida, Debaryomyces, Endomycopsis, Hansenula,
      Pichia, Saccharomyces and Trichosporon spp.) and filamentous fungi (Amylomyces,
      Aspergillus, Mucor, and Rhizopus spp.) contribute to desirable modifications of
      taste, flavour, acidity, digestibility, and texture in non-alcoholic beverages
      (e.g., uji, and ben-saalga), porridges (e.g., mawe) and cooked gels (e.g.,
      kenkey, idli, and mifen). In addition, alcoholic beverages (beers such as
      tchoukoutou and jnard; and spirits e.g. jiu) are obtained using malt, or using
      amylolytic mixed microbial starter cultures as generators of fermentable
      substrates. Wet processing, marketing of multi-purpose intermediate products, co
      fermentation for texture and nutrition, and mixed culture fermentations as
      practiced in indigenous fermentation processes are of interest for industrial
      innovation and for better control of natural mixed culture fermentation systems.
      On the other hand, the nutritional properties of traditional cereal fermented
      products can be enhanced by increasing their nutrient and energy density, as well
      as by increasing their mineral status by combining mineral fortification and
      dephytinization.

PMID- 19747602
TI  - Sourdough and cereal fermentation in a nutritional perspective.
AB  - Use of sourdough is of expanding interest for improvement of flavour, structure
      and stability of baked goods. Cereal fermentations also show significant
      potential in improvement and design of the nutritional quality and health effects
      of foods and ingredients. In addition to improving the sensory quality of whole
      grain, fibre-rich or gluten-free products, sourdough can also actively retard
      starch digestibility leading to low glycemic responses, modulate levels and
      bioaccessibility of bioactive compounds, and improve mineral bioavailability.
      Cereal fermentation may produce non-digestible polysaccharides, or modify
      accessibility of the grain fibre complex to gut microbiota. It has also been
      suggested that degradation of gluten may render bread better suitable for celiac
      persons. The changes in cereal matrix potentially leading to improved nutritional
      quality are numerous. They include acid production, suggested to retard starch
      digestibility, and to adjust pH to a range which favours the action of certain
      endogenous enzymes, thus changing the bioavailability pattern of minerals and
      phytochemicals. This is especially beneficial in products rich in bran to deliver
      minerals and potentially protective compounds in the blood circulation. The
      action of enzymes during fermentation also causes hydrolysis and solubilisation
      of grain macromolecules, such as proteins and cell wall polysaccharides. This
      changes product texture, which may affect nutrient and non-nutrient absorption.
      New bioactive compounds, such as prebiotic oligosaccharides or other metabolites,
      may also be formed in cereal fermentations.

PMID- 19747603
TI  - Metabolic impact and potential exploitation of the stress reactions in
      lactobacilli.
AB  - Lactic acid bacteria (LAB) are a functionally related group of organisms known
      primarily for their bioprocessing roles in food and beverages. The largest
      variety of metabolic properties is found in the group of lactobacilli the vast
      majority of which has been isolated in cereal environments, namely sourdoughs, in
      which their role ranges from sporadic contaminants to major fermentative flora.
      Growth or survival in each of these environmental niches depends on the ability
      of the organism to sense and respond to varying conditions such as temperature,
      pH, nutrients availability and cell population density. Fermentation process
      conditions, including temperature range, dough yield, oxygen, pH as well as the
      amount and composition of starter cultures, determine the cells' metabolic
      response. In fact, the exposure of microbial cells to stressful conditions during
      fermentation involves a broad transcriptional response with many induced or
      repressed genes. The complex network of such responses, involving several
      metabolic activities will reflect upon the metabolome of the fermentative flora,
      and thus on the composition and organoleptic properties of the final products.
      This review shall provide insight into stress response mechanisms and delineate
      the vast potential residing in the exploitation of the stress dependent
      metabolome of LAB focusing on bacteria of the sourdough environment as one of the
      richest sources of lactobacilli.

PMID- 19747604
TI  - Novel metabolites from cereal-associated lactobacilli - novel functionalities for
      cereal products?
AB  - Predictions from genome sequence data of sourdough lactobacilli, novel
      applications of known metabolic traits such as glycansucrases, as well as the
      exploitation of biodiversity of lactobacilli from traditional fermentations
      remain an important resource for identification of novel metabolic traits of
      lactobacilli for use in bread production and the production of value-added food
      ingredients. Cornerstones of heterofermentative lactic metabolism in cereal
      fermentations are the rapid utilization of maltose as preferred carbon source,
      and the production of lactate, CO(2), and the alternative products ethanol and
      acetate. This review will highlight selected novel aspects of carbohydrate
      metabolism that are related to the production of maltose and the utilisation of
      lactate by lactobacilli in cereal fermentations. Several species of lactobacilli
      convert glycerol and lactate to 1,3 and 1,2 propanediol, respectively. Both
      metabolic pathways are relevant for food preservation as reuterin is an
      intermediate of 1,3 propanediol formation, and 1,2 propanediol is further
      converted to propionate. Glycansucrases, disaccharide hydrolases and disaccharide
      phosphorylases catalyse oligosaccharide formation from sucrose, maltose, or
      lactose. Lactobacilli in sourdough generally harbour several enzymes capable of
      oligosaccharide formation from disaccharides. Oligosaccharide formation by
      sourdough lactobacilli can be exploited for fermentative production of novel
      oligosaccharides in bread and a wide spectrum of other food applications.

PMID- 19747605
TI  - The arginine deiminase pathway of Lactobacillus fermentum IMDO 130101 responds to
      growth under stress conditions of both temperature and salt.
AB  - The arginine deiminase (ADI) pathway is a means by which certain sourdough lactic
      acid bacteria (LAB) convert arginine into ornithine via citrulline while
      producing ammonia and ATP, thereby coping with acid stress and gaining an
      energetic advantage. Lactobacillus fermentum IMDO 130101, an isolate from a
      spontaneous laboratory rye sourdough, possesses an ADI pathway which is modulated
      by environmental pH. In the present study, a broader view of the activity of the
      ADI pathway in response to growth under two other commonly encountered stress
      factors, temperature and added salt, was obtained. In both cases, an increase in
      ornithine production was observed as a response to growth under both temperature
      and salt stress conditions. Biokinetic parameters were obtained to describe the
      kinetics of the ADI pathway as a function of temperature and added salt. The
      arginine conversion rate increased as a function of added NaCl concentrations but
      was hardly affected by temperature. In addition, arginine-into-citrulline
      conversion rate was not affected by temperature but increased with increasing
      NaCl concentrations. Citrulline-into-ornithine conversion rate increased with
      increasing temperature, while it dropped to zero with added salt. These findings
      suggest a more pronounced adaptation of the strain through the ADI pathway to
      added salt, as compared with different constant temperatures. Furthermore, these
      results suggest that the ADI pathway in L. fermentum IMDO 130101 is active in
      adapting to non-optimal growth conditions.

PMID- 19747606
TI  - Comparative study of culture media used for sourdough lactobacilli.
AB  - Eleven culture media were analysed to compare their exhaustiveness for the
      quantification of lactobacilli type I sourdoughs. The media tested were MRS,
      maltose modified MRS, MRS5, SDB, SFM, MRS "Vogel", Rogosa as elective media, and
      FH, OH, LAMVAB, KCA as selective media. Six broth media were also tested for
      colony subculture. Quantitatively, maltose MRS and MRS media showed the highest
      counts - respectively 9.47 and 9.43 mean log(cfu)/g. SFM and Rogosa media
      presented slighlty lower levels - 9.1 and 9.24 log(cfu)/g respectively. Levels on
      the remaining media were significantly lower - lesser than 0.5 log(cfu)/g
      compared to maltose MRS and MRS media. From a qualitative standpoint, the
      bacterial diversity, based on the comparison of the whole-cell protein patterns
      of isolates, was the largest on maltose MRS medium. However, MRS5 medium allowed
      the isolation of a specific population only found on this medium. For colony
      subculture, maltose MRS and MRS5 appeared the most appropriate broth media. These
      results underline that there is no really efficient medium for the systemic study
      of sourdoughs. Therefore, the first step before working on these ecosystems
      implies a deliberate choice of the most appropriate media combination.

PMID- 19747607
TI  - In situ production and analysis of Weissella confusa dextran in wheat sourdough.
AB  - Several lactic acid bacteria belonging to the genera Leuconostoc, Lactobacillus,
      and Weissella have been introduced to wheat sourdough baking for in situ
      production of exopolysaccharides. This is considered a novel method for improving
      the shelf-life, volume and nutritional value of bread without additives. However,
      in situ production of exopolysaccharides during sourdough fermentation is
      challenged by simultaneous acidification due to metabolic activities of the
      bacteria, which may significantly diminish the positive technological impact of
      exopolysaccharides. In this study, the growth, activity and in situ production of
      dextran by Weissella confusa VTT E-90392 in wheat sourdoughs were investigated.
      Furthermore, the influence of dextran-enriched sourdoughs, at the addition level
      of 43%, on the subsequent bread quality was established. W. confusa efficiently
      produced dextran from the added sucrose in wheat sourdough without strong acid
      production. A new specific enzyme-assisted method for in situ analysis of dextran
      in sourdoughs was developed. With this method, we could for the first time proof
      significant (11-16 g/kg DW) production of polymeric dextran in sourdoughs.
      Concomitant formation of shorter isomaltooligosaccharides by W. confusa was also
      detected. The produced dextran significantly increased the viscosity of the
      sourdoughs. Application of dextran-enriched sourdoughs in bread baking provided
      mildly acidic wheat bread with improved volume (up to 10%) and crumb softness (25
      40%) during 6 days of storage. Hence, W. confusa is a promising new strain for
      efficient in situ production of dextrans and isomaltooligosaccharides in
      sourdoughs without strong acidification.

PMID- 19747608
TI  - Microbiological and technological characterization of sourdoughs destined for
      bread-making with barley flour.
AB  - The aim of the present study was the microbiological and technological
      characterization of laboratory- made sourdoughs for use in barley-flour-based
      bread-making. A defined multi-strain starter culture consisting of selected
      lactic acid bacteria (LAB) and yeasts from wheat sourdoughs was inoculated into
      three flour-water mixtures, composed of: (i) 100% wheat flour (ii) 50% wheat
      flour and 50% hull-less barley flour (composite flour); (iii) 100% hull-less
      barley flour. After two months of continuous propagation, the chemical
      characteristics of the three sourdoughs were investigated by measuring: pH, total
      titratable acidity and concentrations of various microbial metabolites by HPLC
      (i.e. lactic, acetic, phenyllactic and butyric acids and diacetyl). The microbial
      traits were studied through viable counts, isolation and typing of LAB and yeasts
      and PCR-DGGE analyses. Only Saccharomyces cerevisiae and Lactobacillus plantarum
      were detectable in the sourdoughs together with other lactobacilli species which
      were different depending on the type of flour blend used. The molecular typing of
      the isolates highlighted that only a few strains among those initially inoculated
      prevailed. The volume increases of the three types of sourdough were also
      investigated and a correlation was seen between an increase in the barley flour
      content and a reduction in the dough volume.

PMID- 19747609
TI  - Morbidity and mortality caused by cardiac adverse events after revascularization
      for critical limb ischemia.
AB  - BACKGROUND: We assessed cardiac adverse events (AEs) after primary lower
      extremity arterial revascularization (LEAR) for critical lower limb ischemia
      (CLI) in order to evaluate the impact of cardiac AEs on the clinical outcome. We
      created an optimized care protocol concerning CLI patients' preoperative work-up
      as well as intra- and postoperative surveillance according to recent important
      literature and guidelines. METHODS: We conducted a prospective analysis of
      clinical outcome after LEAR using patient-related risk factors, comorbidity,
      surgical therapy, and AEs. This cohort was divided into patients with and without
      AEs. AEs were categorized according to predefined standards: minor, surgical,
      failed revascularization, and systemic. The consequences of AEs were reoperation,
      additional medication, irreversible physical damage, and early death. RESULTS:
      There were 106 patients (Fontaine III n=49, 46%, and Fontaine IV n=57, 56%) who
      underwent primary revascularization by bypass graft procedure (n=67, 63%) or
      balloon angioplasty (n=39, 37%). No difference in comorbidity was registered
      between the two groups. Eighty-four AEs were registered in 34 patients (32%).
      Patients experiencing AEs had significantly less antiplatelet agents (without AEs
      n=63, 88%, vs. with AEs n=18, 53%; p=0.000) and/or beta-blockers (without AEs
      n=66, 92%, vs. with AEs n=16, 47%; p=0.000) compared to patients without AEs. The
      two most harmful consequences of AEs were irreversible physical damage (n=3) and
      early death (n=8). Sixty percent (n=9) of systemic AEs were heart-related. The
      postprocedural mortality rate was 7.5%, with a 75% (n=6) heart-related cause of
      death. CONCLUSION: AEs occur in >30% of CLI patients after LEAR. The most harmful
      AEs on the clinical outcome of CLI patients were heart-related, causing increased
      morbidity and death. Significant correlations between prescription of beta
      blockers and antiplatelet agents and prevention of AEs were observed. A
      persistent focus on the prevention of systemic AEs in order to ameliorate the
      outcome after LEAR for limb salvage remains of utmost importance. Therefore, we
      advise the implementation of an optimized care protocol by discussing patients in
      a strict manner according to a predetermined protocol, to optimize and
      standardize the preoperative work-up as well as intra- and postoperative patient
      surveillance.

PMID- 19747610
TI  - The anastomosis angle is a key to improved long-term patency of proximal
      femoropopliteal bypass.
AB  - BACKGROUND: Femoropopliteal bypass is a common vascular reconstructive procedure.
      A significant proportion of bypasses become ineffective within 1 year because of
      occlusion due to progression of intimal hyperplasia (IH). METHODS: The clinical
      part of the study involved an analysis of 43 patients with proximal
      femoropopliteal bypass, which became occluded no later than 1 year from the
      procedure, who were successfully treated with thrombolysis. Morphological changes
      of intima in the anastomosis (evaluated angiographically) and the angle of the
      distal end-to-side anastomosis were evaluated. In the second part of the study,
      blood flow in the distal end-to-side anastomosis was modeled experimentally (by
      particle image velocimetry) and numerically (by computational fluid dynamics).
      The results were correlated with the previously identified locations of IH.
      RESULTS: We proved that the locations of IH correlate with the locations of
      disturbed blood flow, increased wall shear stress, and stagnation points as
      documented by experimental visualization and angiographic findings. We also
      confirmed that anastomoses with more acute angles are less prone to IH and
      occlusion of the lumen. CONCLUSION: We suggest that a better understanding of the
      hemodynamics and its influence on IH should lead to an optimized graft design by
      adopting a more acute angle of the anastomosis.

PMID- 19747611
TI  - Safety of carotid endarterectomy in patients concurrently on clopidogrel.
AB  - BACKGROUND: Clopidogrel (Plavix) usage is increasing, primarily for the
      management of patients with cerebrovascular symptoms and for those receiving drug
      eluting coronary artery stents. A significant percentage of these patients will
      require carotid endarterectomy (CEA) while they are receiving clopidogrel. Recent
      data have demonstrated an increased incidence of coronary stent thrombosis when
      clopidogrel is discontinued. The objective of this study was to determine if CEA
      could be performed safely while patients are continued on clopidogrel therapy.
      METHODS: A retrospective cohort design was employed to review consecutive
      patients who underwent CEA over a 24-month period ending March 2007. Patients
      were divided into two groups based on the perioperative use of clopidogrel.
      Preoperative demographics and postoperative results were compared between the two
      groups and statistically analyzed. RESULTS: Of the 100 patients who underwent
      CEA, 19 were taking clopidogrel within 5 days of surgery. This comprised the
      study group. The control group consisted of the 81 patients who did not receive
      clopidogrel. Heparin anticoagulation was routinely utilized prior to clamping in
      both groups. Demographics were similar between the groups. There were no
      statistical differences in morbidity or mortality between the control group and
      the clopidogrel group. Combined stroke/death rates were equivalent between the
      two groups (1.2% control vs. 0% clopidogrel). One hematoma developed in the
      control group, which did not require operative intervention. CONCLUSION: In this
      series, our results suggest that patients concurrently on clopidogrel can safely
      undergo CEA without increased risk of hematoma or neurological complications. In
      view of recent data demonstrating adverse outcomes in patients discontinuing
      clopidogrel, this study is useful in optimally managing this group of patients.

PMID- 19747612
TI  - Management of carotid body tumors and familial paragangliomas: review of 30
      years' experience.
AB  - BACKGROUND: Carotid body tumors (CBTs), especially familial paragangliomas, are
      rare benign neoplasms, accounting for <0.5% of all tumors; and they are the most
      common extra-adrenal paraganglioma. METHODS: In this study, CBTs were clinically
      suspected in 31 patients but diagnosed by histopathology in 28 between 1977 and
      2007 at our department. All but one was operated upon. The ages of the 30
      surgically treated patients ranged 17-73 years. A mass in the neck was the common
      symptom in all patients. Two of the 28 patients with CBTs had a familial
      paraganglioma history of CBT. RESULTS: Twenty-eight of these 30 surgically
      treated patients had confirmed CBT by histopathology; the diagnoses of other two
      patients were neurofibroma in one and tuberculosis lymphadenitis in one. These
      two patients were excluded from the study. CBTs were resected without a shunt
      procedure. UltraCision was used in five patients for tumor resection; the
      surgical results of these patients were excellent (easy dissection, minimal
      hemorrhage and time operation). Twenty patients underwent total resection, six
      had resection and saphenous vein interposition, one had partial resection, and
      one had carotid artery ligation with no resultant neurological deficit. One case
      of hypoglossal paralysis and one benign recurrence were detected. No mortality or
      malignant course was observed. CONCLUSION: CBTs are infrequent neoplasms; their
      surgical treatment is highly dependent on the ability and experience of the
      surgeon. The diagnostic and therapeutic relevance reside in making a timely
      diagnosis to propose a surgical treatment aimed at preventing complications and
      neurological damage. Surgical resection is usually definitive therapy for these
      lesions.

PMID- 19747613
TI  - Use of the StarClose device for closure of inadvertent subclavian artery
      punctures.
AB  - PURPOSE: The placement of central catheters is a common procedure. It is also
      associated with multiple known complications. One of the potential complications
      that carry high morbidity and morality is arterial puncture and cannulation.
      Herein, we describe five case reports of a central line that was inadvertently
      placed in the subclavian artery and successfully removed using a StarClose device
      (Abbott Laboratories, Redwood CA). METHODS/RESULTS: A retrospective chart review
      of a prospectively maintained database was performed. We identified five cases of
      inadvertent subclavian artery cannulation during central venous catheter
      placement. All catheters were removed successfully either in the operating room
      under fluoroscopic guidance or at the bedside with closure of the arteriotomy
      using the StarClose device. No cases required conversion to an open procedure for
      repair. No postremoval hematomas, bleeding episodes, myocardial infarctions,
      arrhythmias, or adverse clinical sequelae were identified. DISCUSSION: Based on
      our limited experience, we feel that this method can be performed safely and
      expeditiously not only in the operating room but also at the bedside.

PMID- 19747614
TI  - Floating caval thrombus arising from the ovarian vein.
AB  - We describe the case of a 37-year-old pregnant woman, who was admitted to
      hospital for suspicion of chorioamnionitis. An emergency C-section was performed.
      Four days later, the patient suffered from abdominal pain and fever. Computed
      tomographic scanning demonstrated only a thrombosis of the right ovarian vein.
      Anticoagulation and antibiotic therapy was started immediately. Color duplex
      imaging performed 3 days later revealed a free-floating caval thrombus reaching
      the confluence of hepatic veins while the patient was fully anticoagulated.
      Emergency thrombectomy was performed by laparotomy, and the thrombus was removed
      by caval incision during suprahepatic clamping of the inferior vena cava. The
      patient recovered rapidly from surgery and was discharged on the tenth
      postoperative day.

PMID- 19747615
TI  - Two anatomic variations of the vertebral artery in four patients.
AB  - In this article, we present four cases of rare anomalous aortic arch and
      vertebral arteries and discuss the possible embryologic etiologies. These include
      two cases in which the right vertebral artery originated from the right common
      carotid artery associated with an aberrant right subclavian artery originating
      from the middle of the aortic arch and two cases in which the left vertebral
      artery had a double origin from the left subclavian artery and aortic arch.

PMID- 19747616
TI  - Aortobilateral axillary bypass to treat severe cerebral ischemia due to
      Takayasu's arteritis.
AB  - Cerebral ischemia resulting from four cervical arterial occlusions due to
      Takayasu's arteritis is a rare condition. Ascending aortounilateral/-bilateral
      internal carotid arterial bypass is a means for relieving it. However,
      postoperative reperfusion syndrome remains an unsolved severe, even fatal
      complication. The following case report reveals new findings. The patient
      presented massive cerebral infarction in the left cerebral hemisphere, four
      cervical arterial lesions, and bilateral subclavian steal syndrome. An ascending
      aorta to bilateral axillary bypass resumed the vertebral blood flow, and as a
      result the patient had a marvelous improvement. Unlike ascending aorta-carotid
      bypass, which directly increases brain perfusion, our procedure does so
      indirectly via axillary arteries. Therefore, there is strong reason to recommend
      ascending aorta to biaxillary bypass for patients with cerebral ischemia due to
      four cervical arterial lesions accompanying a bilateral subclavian steal
      phenomenon that has reversed vertebral flow.

PMID- 19747617
TI  - Renal function impairment in peripheral arterial disease: an important parameter
      that should not be neglected.
AB  - A considerable percentage of patients with peripheral arterial disease (PAD) have
      impaired renal function. We searched the literature (PubMed/Medline) to determine
      the clinical significance and assess the management of renal dysfunction in these
      patients. The results of our literature search suggest that impaired renal
      function is a frequent finding in patients with PAD. The presence of concomitant
      renal dysfunction in these patients is associated with higher morbidity and
      mortality rates, as well as the occurrence of cardiovascular events (stroke,
      myocardial infarction, and vascular death). Additionally, impaired renal function
      negatively affects survival, limb salvage, and graft patency rates when these
      patients undergo lower extremity revascularization procedures. The use of statins
      and angiotensin-converting enzyme (ACE) inhibitors is associated with improved
      renal function and reduced cardiovascular risk in patients with PAD. Based on
      current evidence, renal function should be assessed and regularly monitored in
      all patients with PAD. More importantly, initiation of appropriate treatment
      (e.g., statins and ACE inhibitors) should be implemented to preserve renal
      function and improve vascular morbidity and mortality in these patients.

PMID- 19747618
TI  - Methodology of clinical epidemiologic research and how to report and
      systematically review it. Editor's note.

PMID- 19747619
TI  - A method for low volume and low Se concentration samples and application to
      paired cerebrospinal fluid and serum samples.
AB  - The well-known beneficial health effects of Se have demanded the development of
      rapid and accurate methods for its analysis. A flow injection (FI) method with
      inductively coupled plasma mass spectrometry (ICP-MS) as a selenium-selective
      detector was optimized. Flow injection was carried out using a Knauer 1100
      smartline inert series liquid chromatograph coupled with a Perkin Elmer DRC II
      ICP-mass spectrometer. For sample injection a Perkin Elmer electronic valve
      equipped with a 25microL sample loop was employed. Before measurement, standards
      or samples were administered with 1microg/L rhodium as internal standard for
      correction of changes in detector response according to changes in sample
      electrolyte concentration. The method characterization parameters are: LOD
      (3sigma criterion): 26ng/L, LOQ (10sigma criterion): 86ng/L, linearity: 0.05
      >10microg/L, r(2)=0.9999, serial or day-to-day precision at 2microg/L: 4.48% or
      5.6%. Accuracy was determined by (a) recovery experiments (CSF spiked with
      2microg/L Se); (b) comparison of FI-ICP-MS measurement with graphite furnace
      atomic absorption (GFAAS) measurements of 1:10 diluted serum samples; (c) Se
      determination in urine and serum control materials. Recovery (a) was 101.4%,
      measurement comparison with GFAAS (b) showed 98.8% (5 serum samples, 1:10 diluted
      in the range of 0.5-1.3microg/L, compared to GFAAS determination, which was set
      to 100%), and accuracy was 96.8% or 105.6% for the serum or urine control
      material. Analysis time per sample was short and typically below 2min for the
      complete measurement, including sample introduction, sample-line purge and
      quadruplicate Se determination. This method was used to determine Se in
      cerebrospinal fluid (CSF) and plasma (here parallel to GFAAS) in 35 paired serum
      and CSF samples. Se determination gave values in the range of 42-130microg/L for
      serum and 1.63-6.66microg/L for CSF. The median for Se in 35 individual CSF
      samples was 3.28microg/L, the mean (+/-SD) was 3.67 (1.35)microg/L, whilst for
      individual serum samples the median was 81microg/L and the mean (+/-SD) was 85
      (26)microg/L. When relating the paired Se concentrations of CSF samples to
      respective serum samples it turned out that Se-CSF (behind blood brain barrier
      (BBB)) is independent on Se-serum concentration (before BBB).

PMID- 19747620
TI  - Investigation of the distribution of elements in snail shell with the use of
      synchrotron-based, micro-beam X-ray fluorescence spectrometry.
AB  - In this study, synchrotron-based micro-beam was utilized for elemental mapping of
      a small animal shell. A thin X-ray spot of the order of approximately 10microm
      was focused on the sample. With this spatial resolution and high flux throughput,
      the X-ray fluorescent intensities for Ca, Mn, Fe, Ni, Zn, Cr and Cu were measured
      using a liquid-nitrogen-cooled 13-element energy-dispersive HpGe detector. The
      sample is scanned in a 'step-and-repeat' mode for fast elemental mapping and
      generated elemental maps at 8, 10 and 12keV. All images are of 10microm
      resolution and the measurement time was 1s per point. The accumulation of trace
      elements was investigated from the soft-tissue in small areas. Analysis of the
      small areas will be better suited to establish the physiology of metals in
      specific structures like small animal shell and the distribution of other trace
      elements.

PMID- 19747621
TI  - Effects of long-term selenium yeast supplementation on selenium status studied in
      the rat.
AB  - To investigate the selenium status during long-term dietary supply of selenium
      yeast, 30-day-old male rats were fed for 379 days a methionine-adequate low
      selenium diet supplemented with 0.2mgSe/kg (selenium-adequate diet) or 1.5mgSe/kg
      (high-selenium diet) in the form of selenium yeast that contained 60% of the
      element as l-selenomethionine. Their selenium load was determined at several
      intervals by neutron activation analysis of the selenium concentrations in the
      main selenium body pools, skeletal muscle and liver. After 64 days the tissue
      selenium concentrations plateaued in both groups and then stayed at that level.
      Compared with the selenium-adequate group, elevated tissue selenium
      concentrations were found in the high-selenium group, but the increase by a
      factor of 3.5 in the muscle and by a factor of 2.3 in the liver was smaller than
      the 7.5-fold increase in the selenium intake. In the selenium-adequate group
      about 50% of the muscle selenium and 30% of the liver selenium and in the high
      selenium group about 85% of the muscle selenium and 70% of the liver selenium
      were estimated to be present in non-selenoprotein forms. During selenium
      depletion the liver glutathione peroxidase activity in the high-selenium group
      remained unaffected for 4 weeks and then decreased more slowly than that in the
      selenium-adequate group. From these results it can be concluded that selenium
      incorporated from the selenium yeast diet into non-selenoprotein forms can serve
      as an endogenous selenium source to maintain selenoprotein levels in periods of
      insufficient selenium supply.

PMID- 19747622
TI  - Serum selenium and selenoprotein P status in adult Danes - 8-year followup.
AB  - Selenium is an essential micronutrient important to human health. The main
      objective of this study is to describe serum selenium and selenoprotein P status
      in two samples of the Danish population. In addition, the influence of various
      factors potentially associated with selenium status was investigated. Blood
      samples from a total of 817 randomly selected subjects from two cities in Denmark
      were analyzed. Half of the samples were collected in 1997-1998 and the other half
      in 2004-2005. Samples from women aged 18-22, 40-45 and 60-65 years, and men aged
      60-65 years were selected for this study. All subjects had filled in a food
      frequency questionnaire (FFQ) and a questionnaire with information about smoking
      habits, alcohol consumption and exercise habits. Mean serum selenium level was
      98.7+/-19.8microg/L and median selenoprotein P level was 2.72 (2.18-3.49)mg/L.
      Serum selenium and selenoprotein P increased with age, and selenoprotein P was
      higher in men than in women. Serum selenium levels decreased by 5% on average
      from 1997-98 to 2004-05 (P<0.001), whereas selenoprotein P level increased
      (P<0.001). The intake of fish correlated weakly with serum selenium level
      (r=0.14, P<0.001) but not with selenoprotein P level. Smoking status, alcohol
      intake, exercise habits, BMI and medicine use did not influence selenium status.
      It is concluded that selenium status in this Danish population is at an
      acceptable level. No major groups with regard to age, sex or lifestyle factors
      could be identified as being in risk for selenium deficiency.

PMID- 19747623
TI  - The effect of selenium supplementation on DTH skin responses in healthy North
      American men.
AB  - The trace element selenium (Se) is essential for immune system development and
      function in animals. However, the exact functions of Se in the human immune
      system and the achievable health benefits from Se supplementation remain unclear.
      To test whether an increased intake of dietary Se affects immune function, we
      conducted a randomized, controlled trial of Se supplementation in healthy free
      living men. Forty-two men were administered 300microg of Se a day as high-Se
      Baker's yeast, or low-Se yeast for 48 weeks. Serum immunoglobulins, differential
      complete blood counts and lymphocyte sub-populations were measured every 6 weeks.
      Tests of delayed-type hypersensitivity (DTH) skin responses to mumps, candida,
      trychophyton, tuberculin-purified protein, and tetanus were performed at baseline
      and at the end of 48 weeks of treatment. Supplementation increased blood Se
      concentration by 50%. Surprisingly, consumption of the low-Se yeast induced
      anergy in DTH skin responses and increased counts of natural killer (NK) cells
      and T lymphocytes expressing both subunits of the high affinity interleukin-2
      receptor (IL2R). DTH skin responses and IL2R+ cells did not change in the high-Se
      group, suggesting Se supplementation blocked induction of DTH anergy. There were
      no differences between groups in quality of life indicators, number of days sick,
      other leukocyte phenotypes, serum immunoglobulins, or complement factors. These
      results suggest that Se plays a role in immunotolerization, a cell-mediated
      process involved in many aspects of immune function.

PMID- 19747624
TI  - Enrichment of fertilizers with zinc: An excellent investment for humanity and
      crop production in India.
AB  - Micronutrient malnutrition is a growing concern in the developing world,
      resulting in diverse health and social problems, such as mental retardations,
      impairments of the immune system and overall poor health. In recent years, the
      zinc (Zn) deficiency problem has received increasing attention and appears to be
      the most serious micronutrient deficiency together with vitamin A deficiency.
      Zinc deficiency is particularly widespread among children and represents a major
      cause of child death in the world. In countries where Zn deficiency is well
      documented as an important public health problem, cereal-based foods are the
      predominant source of daily calorie and protein intake. Because the concentration
      of Zn in cereal crops is inherently very low, growing cereals on potentially Zn
      deficient soils further decreases grain Zn concentrations. It is, therefore, not
      surprising that high Zn deficiency incidence in humans occurs predominantly on
      areas where soils are deficient in plant-available Zn, as shown in many Southeast
      Asian countries. India has some of the most Zn-deficient soils in the world.
      Nearly 50% of cultivated soils in India are low in plant-available Zn; these
      soils are under intensive cultivation of wheat and rice with no or little
      application of Zn fertilizers. Consequently, cereal crops grown on such Zn
      deficient soils contribute only marginally to daily Zn intake. In the rural areas
      of India, rice and wheat contributes nearly 75% of the daily calorie intake.
      These facts clearly point to an urgent need for improved Zn concentration of
      cereal grains in India. Recent calculations indicate that biofortification
      (enrichment) of rice and wheat grain with Zn, for example by breeding, may save
      lives of up to 48,000 children in India annually. Breeding new cereal genotypes
      for high grain Zn concentration is the most realistic and cost-effective strategy
      to address the problem. However, this strategy is a long-term one, and the size
      of plant-available Zn pools in soils may greatly affect the capacity of Zn
      efficient (biofortified) cultivars to take up Zn and accumulate it in grains.
      Therefore, application of Zn-containing fertilizers represents a quick and
      effective approach to biofortifying cereal grains with Zn, thus being an
      excellent complementary tool to the breeding strategy for successful
      biofortification of cereals with Zn. Increasing evidence is available from field
      trials showing that soil and/or foliar application of Zn fertilizers improves
      grain Zn concentration up to 2- or 3-fold. In the countries where Zn deficiency
      is both a public health issue and an important soil constraint to crop
      production, like in India, enrichment of widely applied fertilizers with Zn would
      be an excellent investment for improving grain Zn while contributing to increased
      crop production. Recent work by the scientists of the Indian Agricultural
      Research Institute indicates that the use of Zn-enriched urea in rice and wheat
      significantly improves both grain Zn concentration and grain yield. It is obvious
      that enrichment of widely applied fertilizers with Zn and/or foliar application
      of Zn fertilizers appear to be a high priority with the strongest potential to
      alleviate Zn deficiency-related problems in India. A Government action and policy
      plan for enrichment of selected major fertilizers with Zn is required urgently.

PMID- 19747625
TI  - Age-dependent expression of hephaestin in the brain of ceruloplasmin-deficient
      mice.
AB  - Aceruloplasminemia is an autosomal recessive disorder caused by mutations in the
      ceruloplasmin (CP) gene. It is characterized by iron accumulation in the brain
      and in visceral organs. However, little is known about the mechanism of iron
      transport in these regions. Adult CP null (CP(-/-)) mice show increased iron
      deposition in several regions of brain, such as the cerebellum and brainstem. In
      this study, we investigated the expression of the ceruloplasmin homolog
      hephaestin (Heph) in the brain of CP(-/-) mice as a function of age. In the
      cerebral cortex and caudate putamen of 80-week-old CP(-/-) mice, the expression
      of Heph increased significantly whilst iron levels remain normal [Patel BN, Dunn
      RJ, Jeong SY, Zhu Q, Julien JP, David S. Ceruloplasmin regulates iron levels in
      the CNS and prevents free radical injury. J Neurosci 2002;22(15):6578-6],
      indicating that Heph might compensate for the loss of CP. In contrast, the
      substantia nigra and cerebellum of 80-week-old CP(-/-) mice accumulate iron but
      do not express high levels or significant decrease of Heph, suggesting that Heph
      does not replace CP in these regions. These data suggest that Heph may compensate
      for the loss of CP in a region-specific manner.

PMID- 19747626
TI  - Induction of necrosis in cadmium-induced hepatic oxidative stress and its
      prevention by the prophylactic properties of taurine.
AB  - The present study has been carried out to investigate the protective role of
      taurine against cadmium (Cd)-induced oxidative impairment in murine liver. Oral
      administration of cadmium chloride (CdCl(2)) at a dose of 4mg/kg body weight for
      6 days increased the accumulation of the Cd in the liver and diminished the liver
      weight to body weight ratio. The CdCl(2) altered the levels of intracellular
      trace elements, cofactors of various metalloenzymes and increased the activities
      of serum marker enzymes related to liver dysfunction. In addition, Cd
      intoxication also attenuated intracellular antioxidant power, the activities of
      antioxidant enzymes as well as the levels of cellular metabolites. Moreover,
      level of hepatic metallothionein, lipid peroxidation, protein carbonylation, DNA
      fragmentation, concentration of intracellular reactive oxygen species (ROS) and
      the activities of cytochrome P450s have been increased due to Cd toxicity. In
      addition to the oxidative impairments, Cd exposure caused hepatic cell death
      mainly via the necrotic pathway. Oral administration of taurine at a dose of
      100mg/kg body weight for 5 days prior to CdCl(2) intoxication prevented the
      alterations of all the toxic-induced hepatic damages. Histological studies also
      supported the beneficial role of taurine against Cd-induced hepatic damages.
      Combining all, results suggest that taurine could protect hepatic tissues against
      Cd-induced oxidative stress probably through its antioxidant activity.

PMID- 19747627
TI  - Metallothionein expression in HaCaT and C6 cell lines exposed to cadmium.
AB  - Metallothioneins (MT) are low-molecular weight, cysteine-rich metal-binding
      proteins. MT play a role in the homeostasis of essential metals such as zinc (Zn)
      and copper (Cu), detoxification of toxic metals such as cadmium (Cd) and
      protection against oxidative stress. In this study, we examined the expression of
      MT in HaCaT and C6 cells as a strategy to enhance protection against Cd-mediated
      toxicity. At basal level, HaCaT cells showed higher MT level than C6 cells which
      could explain the resistance of HaCaT cells. Western blot showed that C6 cells
      treated with 20micromol/L Cd for 24h did not express any MT. MT were initially
      expressed in the cytoplasmic or periplasmic compartment and were then
      translocated in the nucleus after 24h treatment by Cd both in HaCaT and C6 cells.
      In addition, the cell treatment with Cd was followed by an increase in the
      cellular zinc level but the electrophoretic mobility shift assay (EMSA)
      experiment did not show any translocation of metal-responsive transcription
      factor-1 (MTF-1) to the nucleus of HaCaT cells. These absence of translocation
      could be due to the presence of MT in these cells at the basal state. The
      translocation study in HaCaT cells suggested that the MT translocation in the
      nucleus was greater than observed in C6 cells. The latter observation could
      explain HaCaT cells resistance to Cd concentrations up to 50micromol/L. Our
      results suggested that the C6 cell sensitivity was correlated with the decrease
      in MT level at 20micromol/L Cd occurring after the transcription of MT gene.

PMID- 19747628
TI  - Involvement of non-enzymatic antioxidant defenses in the protective effect of
      diphenyl diselenide on testicular damage induced by cadmium in mice.
AB  - The involvement of non-enzymatic antioxidant defenses in the protective effect of
      diphenyl diselenide (PhSe)(2) on testicular damage caused by cadmium in mice was
      investigated. Mice received a single dose of CdCl(2) (5mg/kg, intraperitoneally).
      Thirty minutes after the CdCl(2) injection, they received a single oral dose of
      (PhSe)(2) (400micromol/kg). Twenty-four hours after CdCl(2) administration, blood
      samples were collected and mice were killed and had their testes dissected.
      Parameters in plasma (aspartate (AST) and alanine (ALT) aminotransferases and
      lactato dehydrogenase (LDH) activities as well as creatinine levels) were
      determined. The activity of delta-aminolevulinate dehydratase (delta-ALA-D), the
      levels of thiobarbituric acid-reactive substances (TBARS), ascorbic acid and
      nonprotein thiols (NPSH) and histological analysis were determined in collected
      samples. Results demonstrated that (PhSe)(2) protected against toxicity induced
      by CdCl(2) on delta-ALA-D activity, ascorbic acid and NPSH levels. (PhSe)(2)
      protected against the increase in plasma AST, ALT and LDH activities caused by
      CdCl(2). Testes of mice exposed to CdCl(2) showed marked histopathological
      alterations that were ameliorated by administration of (PhSe)(2). (PhSe)(2)
      protected against toxicity induced by CdCl(2) in testes of mice. Ascorbic acid
      and NPSH, non-enzymatic antioxidant defenses, are involved in the protective
      effect of (PhSe)(2) against testicular damage caused by CdCl(2) in mice.

PMID- 19747630
TI  - Targeting Treg cells in situ: emerging expansion strategies for (CD4(+)CD25(+))
      regulatory T cells.
AB  - Recognition of the ability of CD4(+)FoxP3(+) T cells (Treg) to influence the
      generation of peripheral immune responses has engendered enthusiasm for the
      development of strategies utilizing these cells to regulate immune responses in
      clinically important settings including transplantation, autoimmunity and cancer.
      A number of studies have reported effective regulation utilizing ex-vivo
      expansion approaches and subsequent transfer of Treg populations in experimental
      models. This commentary discusses recently emerging strategies to activate and
      expand Treg cells in situ which include antibodies, antigen presenting cells and
      the use of IL2 / anti-IL2 antibody complex. The development of reagents which can
      stimulate and / or remove Treg cells in situ would represent an important advance
      towards facilitating new opportunities to harness this compartment for the
      augmentation of 'wanted' or suppression of 'unwanted' immune responses.
      Simultaneous targeting of multiple molecules on Treg cells may ultimately enable
      more effective control of this regulatory sector.

PMID- 19747631
TI  - Delaying DLA-haploidentical hematopoietic cell transplantation after total body
      irradiation.
AB  - Exposure to accidental or deliberate radiation poses a threat to public health,
      proving lethal at higher doses in large part because of deleterious effects on
      marrow. In those cases, allogeneic hematopoietic cell transplantation (HCT) might
      be required to restore marrow function. Most radiation accident victims will have
      HLA-haploidentical relatives who could serve as HCT donors. Here, we assessed in
      a canine HCT model the total body irradiation (TBI) doses after which transplants
      might be required and successful engraftment would be possible. In an attempt at
      mimicking the logistical problems likely to exist after radiation accidents, 4-,
      8- or 10-day intervals were placed between TBI and HCT. To keep the experimental
      readout simple, no graft-versus-host disease (GVHD) prevention was administered.
      All dogs transplanted after a 4-day delay following 700 or 920 cGy TBI
      successfully engrafted, whereas virtually all those given 450 or 600 cGy rejected
      their grafts. Transplant delays of 8 and 10 days following 920 cGy TBI also
      resulted in successful engraftment in most dogs, whereas a delay of 8 days after
      700 cGy resulted in virtually uniform graft failure. The time courses of acute
      GVHD (aGVHD) and rates of granulocyte recovery in engrafting dogs were comparable
      among dogs regardless of the lengths of delay. In other studies, we showed that
      most dogs not given HCT survived 700 cGy TBI with intensive supportive care,
      whereas those given 800 cGy TBI and higher died with marrow aplasia. Thus, DLA
      haploidentical HCT was successful even when carried out 4, 8, or 10 days after
      TBI at or above radiation exposures where dogs survived with intensive care
      alone.

PMID- 19747632
TI  - Chronic kidney dysfunction in patients alive without relapse 2 years after
      allogeneic hematopoietic stem cell transplantation.
AB  - Allogeneic hematopoietic stem cell transplantation (HSCT) is the treatment of
      choice for a wide range of diseases, but is associated with a significant risk of
      chronic kidney disease (CKD), affecting up to 25% of survivors with a significant
      morbidity. The causes of CKD after HSCT vary between different studies. The
      present study evaluated CKD in patients undergoing allogeneic HSCT. We analyzed
      the clinical course of 148 patients who received allogeneic HSCT at the
      University Hospital of St. Louis in Paris between 1999 and 2002 and were alive
      after 2 years without relapse. CKD was defined as a glomerular filtration rate
      (GFR) <60 mL/min/1.73 m(2), using the abbreviated modification of diet in renal
      disease (MDRD) equation for adults and the Schwartz formula for children. Of the
      148 relapse-free 2-year survivors, 11 (7%) patients had renal dysfunction. No
      chronic renal failure was noted in the younger age group (<15 years at
      transplantation). CKD was associated with total body irradiation (TBI) (odds
      ratio [OR] = 4.53; 95% confidence interval [CI] 1.15 to 17.9; P = .026) and
      chronic graft-versus-host disease (cGVHD) (OR = 4.58; 95% CI 1.16-18.1; P =
      .026). Only 1 additional patient developed CKD between 2 and 5 years of follow-up
      (cumulative incidence of 0.7% over the 3-year period). In the CKD group, renal
      function tended to stabilize over the 3-year period (estimated GFR 45 +/- 14
      mL/min/1.73 m(2) at 2 years and 46 +/- 14 mL/min/1.73 m(2) at 5 years). A 7%
      prevalence of CKD was noted in the relapse-free 2-year survivor patients. Renal
      impairement was correlated with TBI and cGVHD. Minor incidence of CKD and a
      relative stability of renal function were noted between 2 and 5 years after HSCT.

PMID- 19747633
TI  - Partially matched related hematopoietic stem cell transplantation without ex vivo
      T cell depletion compared with matched unrelated transplantation in adult
      patients with hematologic malignancies.
AB  - The optimal alternative donor for adult hematopoietic stem cell transplantation
      (HSCT) candidates who lack an ideal histocompatible sibling remains
      controversial. We studied the clinical outcomes of 88 adult patients with
      hematologic malignancies who received a partially matched related donor (PMRD)
      transplant (n=36) or a matched unrelated donor (MUD) transplant (n=52) with a
      uniform myeloablative protocol without ex vivo T cell depletion. Age and other
      characteristics were comparable in the 2 groups, except that the PMRD group had a
      higher proportion of bone marrow (BM) grafts. Primary engraftment was achieved in
      nearly 98% of the whole cohort. The incidences of acute grade III-IV and
      extensive chronic graft-versus-host disease (aGVHD, cGVHD) were 15% and 16% in
      the PMRD group and 16% and 14% in the MUD group. Although treatment-related
      mortality (TRM) was 42% in the PMRD group and 31% in the MUD group (P=.29), the
      relapse rate was<11% for the whole cohort. With a median follow-up of 30 months,
      no statistically significant difference was observed in 3-year overall survival
      (OS) and event-free survival (EFS) between the PMRD group (45% and 38%) and the
      MUD group (54% and 50%). These data demonstrate that HSCT performed with PMRD can
      be an alternative option for treating adult patients with hematologic
      malignancies.

PMID- 19747634
TI  - Outcome of allogeneic hematopoietic stem cell transplantation in patients with
      low left ventricular ejection fraction.
AB  - A high risk of regimen-related toxicity with allogeneic hematopoietic stem cell
      transplantation (allo-HSCT) limits this potentially curative treatment for
      patients with a left ventricular ejection fraction (LVEF) of > or =50%. We
      evaluated the frequency of cardiac complications and 100-day nonrelapse mortality
      (NRM) in 56 patients with a LVEF of < or =45%, who received allo HCT at our
      institution. The results were retrospectively compared with a matched control
      group with LVEF of > or =50%, which received an allogeneic stem cell
      transplantation (allo-SCT). After a median follow-up of 29 months in the study
      group, grade > or =2 cardiac complications were seen in 7 of 56 (12.5%) patients
      and cumulative incidence of 100-day NRM was 12.5% with no deaths from cardiac
      causes. In contrast, after a median follow-up of 49 months in the control group,
      grade >2 cardiac complications were seen in 19 of 161 patients (11.8%; P = 1.00)
      and cumulative incidence of 100-day NRM was 14.9% (P = .82). The presence of at
      least 1 of the 7 pretransplant cardiac risk factors (past history of smoking,
      hypertension, hyperlipidemia, coronary artery disease, arrhythmia, prior
      myocardial infarction, and congestive heart failure) was associated with a higher
      cardiac complication rate in the study group (P = .03). In conclusion, selected
      patients with a LVEF of < or =45% can safely receive allo-HCT without a
      significant increase in cardiac toxicity or NRM.

PMID- 19747635
TI  - Osteochondroma after hematopoietic stem cell transplantation in childhood. An
      Italian study on behalf of the AIEOP-HSCT group.
AB  - A retrospective study was conducted among Italian children treated with
      hematopoietic stem cell transplant (HSCT) to evaluate the incidence and risk
      factors in the development of osteochondroma (OC). OC occurred in 27 patients who
      received autologous or allogeneic HSCT. The estimated 5-, 10-, and 15-year
      cumulative risk of developing OC was 0.5%, 3.2%, and 6.1%, respectively. Analysis
      of cumulative risk stratified by the various risk factors revealed that male sex
      (P=.026), autologous HSCT (P=.001), age at HSCT (< or =3 years) (P < .0001), and
      total body irradiation (TBI) (P <.0001) significantly affected the risk of OC.
      Multivariate analysis, restricted only to tumor types with at least 1 case of OC,
      showed that earlier age at HSCT (P =.0004) and TBI (P < .0001) were the only
      factors that were significantly associated with OC.

PMID- 19747636
TI  - The effect of smoking on allogeneic transplant outcomes.
AB  - Using the Center for International Blood and Marrow Transplant Research (CIBMTR)
      data, we compared the transplant outcomes of patients with chronic myelogenous
      leukemia (CML) who were nonsmokers (NS) and past or current smokers (PCS). There
      were 2193 NS and 625 PCS who received matched sibling and unrelated donor
      allografts for CML in first chronic phase. We looked for dose effects and
      identified low and high dose smoking groups (>10 pack years, >1 pack per day).
      Outcomes were adjusted for known prognostic variables including the European
      Group for Blood and Marrow Transplant (EBMT) risk score. In multivariate analyses
      of sibling allograft recipients, relapse risk (RR) was higher (RR=1.67, P=.003)
      in smokers than NS, but the dose effects were not consistent. High-dose smokers
      experienced a 50% treatment-related mortality (TRM) versus 28% in the NS group at
      5 years on univariate analysis, and the RR was 1.57 (P=.005) on multivariate
      analysis. Overall survival (OS) at 5 years was 68% in NS versus 62% in the low
      dose smoking group versus 50% in the high-dose smoking group (P < .001). Smoking
      did not significantly affect outcomes in unrelated donor recipients, but numbers
      were smaller. High-dose smoking is associated with a reduction in OS in patients
      having sibling allografts for CML. A prospective study with detailed demographic,
      pulmonary function, and quality-of-life data would improve our understanding of
      this issue.

PMID- 19747637
TI  - Classic and overlap chronic graft-versus-host disease (cGVHD) is associated with
      superior outcome after extracorporeal photopheresis (ECP).
AB  - The National Institutes of Health (NIH) classification of graft-versus-host
      disease (GVHD) is a significant improvement over prior classifications, and has
      prognostic implications. We hypothesized that the NIH classification of GVHD
      would predict the survival of patients with GVHD treated with extracorporeal
      photopheresis (ECP). Sixty-four patients with steroid refractory/dependent GVHD
      treated with ECP were studied. The 3-year overall survival (OS) was 36% (95%
      confidence interval [CI] 13-59). Progressive GVHD was seen in 39% of patients
      with any acute GVHD (aGVHD) (classic acute, recurrent acute, overlap) compared to
      3% of patients with classic chronic GVHD (cGVHD) (P=.002). OS was superior for
      patients with classic cGVHD (median survival, not reached) compared to overlap
      GVHD (median survival, 395 days, 95% CI 101 to not reached) and aGVHD (delayed,
      recurrent or persistent) (median survival, 72 days, 95% CI 39-152). In univariate
      analyses, significant predictors of survival after ECP included GVHD subtype,
      bilirubin, platelet count, and steroid dose. In multivariate analyses overlap
      plus classic cGVHD was an independent prognostic feature predictive of superior
      survival (hazard ratio [HR] 0.34, 95% CI 0.14-0.8, p=.014). This study suggests
      that NIH classification can predict outcome after ECP for steroid
      refractory/dependent GVHD.

PMID- 19747638
TI  - Interferon gamma 13-CA-repeat homozygous genotype and a low proportion of CD4(+)
      lymphocytes are independent risk factors for cytomegalovirus reactivation with a
      high number of copies in hematopoietic stem cell transplantation recipients.
AB  - Cytomegalovirus (CMV) reactivation was analyzed in 92 recipients of allogeneic
      hematopoietic stem cell transplantation (HSCT) in relation to the proportion of
      CD4(+) lymphocytes in blood and a microsatellite polymorphism within the first
      intron of the interferon-gamma (IFNG) gene. CMV reactivation was found in 50% of
      the HSCT recipients; in 30% of these individuals, the level of CMV copies
      exceeded 100 per 10(5) peripheral blood (PB) cells on at least one occasion
      during the 100-day post-HSCT observation period. This high CMV copy level was
      most frequently found between 31 and 60 days post-HSCT (P = .021). Patients with
      > or = 100 CMV copies/10(5) cells were characterized by poorer overall survival
      (OS) compared with those lacking CMV copies or having < 100 CMV copies/10(5)
      cells (P = .04), and they suffered from severe post-HSCT complications, including
      acute graft-versus-host disease (aGVHD) and relapse. Thus, patients with > or =
      100 CMV copies/10(5) cells were designated as having clinically significant CMV
      reactivation. Patients with < 10% CD4(+) lymphocytes had a higher number of CMV
      DNA copies than those with higher proportions of CD4(+) lymphocytes (0.62 vs
      0.21, P = .001; mean +/- SEM, 4422 +/- 1667 vs 937 +/- 662 CMV copies/10(5)
      cells, P < .001, for the proportion of cases with reactivation and numbers of
      copies, respectively). Similarly, patients carrying 2 IFNG 13-CA-repeat alleles
      (homozygotes) had more frequent CMV reactivation (0.50 vs 0.26; P = .039) and a
      higher CMV load (4111 +/- 1699 vs 950+/-591 CMV copies/10(5) cells; P = .041)
      compared with those with other IFNG microsatellite allele constellations.
      Multivariate analysis demonstrated that the IFNG 13-CA-repeat homozygous genotype
      (odds ratio [OR] = 0.221; P = .044), a low proportion of CD4(+) lymphocytes (OR =
      0.276; P = .050), and a lack of optimal (10/10 alleles) donor-recipient HLA match
      (OR = 15.19; P = .006) were independent risk factors for CMV reactivation with a
      high number of copies.

PMID- 19747639
TI  - Autologous hematopoietic stem cell transplantation as an intensive consolidation
      therapy for adult patients in remission from acute myelogenous leukemia.
AB  - Autologous peripheral blood stem/progenitor cell transplantation (APBSCT) has
      been investigated as a potential therapeutic option to improve outcome in
      patients with acute myelogenous leukemia (AML). However, its optimal role in
      treatment for adults in remission has not been clearly established. We performed
      a retrospective analysis on 45 patients aged 21 to 73 years (median 51 years)
      with de novo AML who underwent APBSCT stratified by age, complete remission
      status, and cytogenetic risk. The 5-year disease-free survival (DFS) for all
      patients was 33.9% (95% confidence interval [CI], 20.1%-53.7%) and overall
      survival (OS) was 43.6% (CI, 29.2%-62.8%). For patients under the age of 60
      years, the 5-year DFS for intermediate and high cytogenetic risk was 53.3% (CI,
      23.5%-85.6%) and 50.0% (CI, 16.1%-100.0%); the 5-year OS for patients under the
      age of 60 years with low, intermediate, and high cytogenetic risk was 80.0% (CI,
      40.0%-100.0%), 60.0% (CI, 31.2%-90.7%), and 75.0% (CI, 39.0%-100.0%),
      respectively. For patients over the age of 60 years, the 5-year DFS and OS for
      intermediate cytogenetic risk was 21.4% (CI, 7.9%-58.4%) and 21.4% (CI, 7.9%
      58.4%). The DFS and OS of these patients are comparable to the historic survival
      of those who underwent allogeneic stem cell transplantation when adjusted by age.
      In addition, there was no treatment-related mortality (TRM). We conclude that
      APBSCT is a reasonable and safe intensive consolidation for patients with AML who
      do not have a suitable HLA-matched donor.

PMID- 19747629
TI  - Guidelines for preventing infectious complications among hematopoietic cell
      transplantation recipients: a global perspective.

PMID- 19747640
TI  - Salvage allogeneic hematopoietic cell transplantation with fludarabine and low
      dose total body irradiation after rejection of first allografts.
AB  - We summarized results in 38 consecutive patients (median age=56 years) with
      hematologic malignancies (n=35), aplastic anemia (n=2), or renal cell carcinoma
      (n=1), who underwent salvage hematopoietic cell transplantation (HCT) for
      allograft rejection. In 14 patients, the original donors were used for salvage
      HCT, and, in 24 cases, different donors were used. Conditioning for salvage HCT
      consisted of fludarabine (Flu) and either 3 or 4 Gy total body irradiation (TBI).
      Sustained engraftment was achieved in 33 patients (87%). Grafts were rejected in
      5 patients (13%), 4 of whom had myelofibrosis. With a median follow-up of 2 years
      (range: 0.3 to 7.8 years), the 2- and 4-year estimated survivals were 49% and
      42%, respectively. The 2-year relapse rate and nonrelapse mortality (NRM) were
      36% and 24%, respectively. The 2-year cumulative incidences of grades II-IV acute
      and moderate-severe chronic graft-versus-host disease (aGVHD, cGVHD) were 42% and
      41%, respectively. In this cohort, TBI dose, grafts from original versus
      different donors, related versus unrelated donors, and HCT comorbidity scores did
      not have an impact on outcomes. We concluded that graft rejection after
      allogeneic HCT could be overcome by salvage transplantation using conditioning
      with Flu and low-dose TBI.

PMID- 19747641
TI  - Relative survival of long-term hematopoietic cell transplant recipients
      approaches general population rates.
AB  - Whether the annual mortality rates of long-term hematopoietic cell transplant
      (HCT) survivors ever return to that of the general population is unclear. This
      study sought to determine the annual long-term mortality rates of allogeneic and
      autologous HCT recipients who had survived 5 years or more disease-free
      posttransplant and calculate their relative survival rates. Patients were
      included if they had a first allogeneic or syngeneic HCT for acute leukemia,
      chronic myelogenous leukemia (CML) or myelodysplastic syndromes (MDS), or
      autologous HCT for acute myelogenous leukemia (AML) or lymphoma in Australia or
      New Zealand between 1992 and 2001, recorded on the Australasian Bone Marrow
      Transplant Recipient Registry (ABMTRR) database, and were known to have survived,
      disease free, 5 years or more posttransplant. The annual mortality rates of 5
      year transplant survivors were compared to standard Australian and New Zealand
      populations using relative survival. A total of 1461 HCT survivors (688
      postallograft, 773 postautograft) were included in this study. The 10-year
      survival probability for 5-year allograft survivors was slightly higher than that
      of 5-year autologous survivors (93.4% versus 89.6%, P=.06). The relative survival
      of both allogeneic and autologous 5-year survivors was never <97% of that of the
      general population. However, it was statistically significantly lower than
      expected in the sixth to ninth years posttransplant, with no obvious pattern of
      either improvement or deterioration from 6 to 10 years posttransplant. This study
      indicates that annual relative survival rates of long-term survivors of
      allogeneic HCT performed in Australia and New Zealand for acute lymophoblastic
      leukemkia (ALL), AML, CML, and MDS are slightly, but significantly lower than
      population rates in the 6th to 10th years posttransplant. Annual relative
      survival rates of long-term survivors of autologous HCT performed in Australia
      and New Zealand for AML and lymphomas are also slightly lower than population
      rates up to the 10th year posttransplant. Late deaths from transplant and disease
      related causes are unusual, but continue to occur for many years post-HCT.

PMID- 19747642
TI  - Oral beclomethasone dipropionate for the treatment of gastrointestinal chronic
      graft-versus-host disease.
AB  - The most common approach for the treatment of chronic graft-versus-host disease
      (cGVHD) has been the long-term use of systemic steroids. Beclomethasone
      dipropionate (BDP) is a topically active corticosteroid with relatively low
      absorption from the gastrointestinal mucosa. It has been successfully used to
      treat acute GVHD (aGVHD), but its use in the cGVHD setting is far more limited.
      In the current study, BDP was administered to 33 patients who underwent
      allogeneic transplantation and had biopsy-proven gastrointestinal cGVHD (GI
      cGVHD). Twenty-six patients with GI cGVHD received BDP as first-line and 7 as
      either second- or third-line treatment. All patients received BDP together with a
      calcineurin inhibitor, except for 1 patient who was also receiving mycophenolate
      mofetil (MMF). BDP was administered for a minimum of 16 weeks and was tapered
      during 4 additional weeks. Of those patients receiving BDP as the first line of
      treatment, 22 (84.6%) achieved complete remission (CR) of GI cGVHD, 2 (7.7%)
      achieved a partial response (PR) and 2 (7.7%) did not respond or progressed.
      Median time to response was 28 days. Nevertheless, only 7 (27%) patients had
      maintained the response at last follow-up, whereas 19 (73%) finally relapsed or
      progressed. Median time to relapse was 147 days after the end of BDP. In the case
      of the patients who received BDP as a second- or third-line treatment, 3 (42.9%)
      achieved CR and 2 (28.6%) PR. For the whole series of patients, 13 patients
      (39.4%) were not receiving immunosuppressive treatment at final follow-up. Only 4
      patients developed cytomegalovirus (CMV) reactivation, which was successfully
      treated with antiviral drugs. No fungal infection was observed during the
      treatment period. In conclusion, the current study shows that BDP, in the absence
      of systemic steroids, is a highly effective initial therapeutic approach for GI
      cGVHD, which helps to avoid complications related to systemic steroids.

PMID- 19747643
TI  - Hematologic safety profile of linezolid in the early periengraftment period after
      allogeneic stem cell transplantation.
AB  - Vancomycin-resistant enterococci (VRE) are common pathogens of bloodstream
      infections in the peritransplantation period. Linezolid is approved by the FDA
      for treating VRE infections, but has been associated with low rates of
      hematologic toxicity in the general population; thus, there are concerns about
      its potential myelotoxicity in the allogeneic hematopoietic stem cell
      transplantation (HSCT) setting. We examined the impact of linezolid treatment on
      the times to neutrophil and platelet engraftment in 33 patients who underwent
      HSCT. In this retrospective case-controlled study conducted from 2000 through
      2007, cases received > or = 7 consecutive days of linezolid therapy, starting
      before day +8 post-HSCT. Controls received > or = 7 consecutive days of
      vancomycin therapy before day +8 and were matched to cases by age and
      conditioning regimen. The cumulative incidence function was used to estimate the
      probabilities for the times to neutrophil and platelet engraftment. A competing
      risk regression model was used to determine whether times to engraftment differed
      for cases and controls. A total of 33 cases were compared with 33 controls. The
      median duration of treatment after stem cell infusion was 14 days (range, 7 to 34
      days) for linezolid and 16 days (range, 8 to 33 days) for vancomycin. The rates
      of neutrophil and platelet engraftment were similar between the cases and
      controls. After adjusting for baseline characteristics, no difference in the
      times to neutrophil or platelet engraftment was seen between the 2 groups. Our
      findings demonstrate no adverse effect on the times to neutrophil or platelet
      engraftment with linezolid use. Larger prospective studies are needed to fully
      determine the hematologic safety of linezolid in patients undergoing HSCT.

PMID- 19747644
TI  - Chances of finding an HLA-matched sibling: The Saudi experience.
AB  - Hematopoietic cell transplantation (HCT) remains the fundamental procedure to
      treat many diseases. Its success depends greatly on the degree of HLA matching
      between donor and recipient. Although the number of successful HCT procedures
      carried out worldwide increases every year, many patients remain unable to
      receive this treatment because of the difficulty of finding an HLA-matching
      donor. In our center, we identified the HLA types for all HCT candidates and
      their siblings in an attempt to determine the chance of finding a full HLA
      matching sibling. Overall, 60% of patients had a chance of finding an HLA
      matching sibling. The chance of finding a matching sibling was 43% in patients
      aged birth to 5 years, compared with 68% in those aged 20+ years. In our Saudi
      population, patients in need of HCT have a greater chance of finding an HLA
      matching sibling than is reported in most Western countries. This is mainly
      because of the larger number of siblings in most Saudi families. Younger children
      requiring HCT have a lesser chance of finding an HLA-matching sibling. Our data
      demonstrate that even in a country with relatively large families, it is still
      essential to consider alternative donor strategies, such as adult unrelated
      donors, unrelated umbilical cord blood units, and haploidentical donors.

PMID- 19747645
TI  - Pandemic influenza: a priority for the neurological community.

PMID- 19747646
TI  - Cervicogenic headache: a pain in the neck for some neurologists?

PMID- 19747647
TI  - Can the WATCHMAN device truly PROTECT from stroke in atrial fibrillation?

PMID- 19747648
TI  - Epidural abscesses in Africa.

PMID- 19747650
TI  - Quality of life in children with CMT type 1A.

PMID- 19747652
TI  - When a patient chooses death: divided attitudes.

PMID- 19747655
TI  - Blood pressure as a prognostic factor after acute stroke.
AB  - Stroke is the second most common cause of death worldwide and is the complication
      of hypertension that is most directly linked to blood pressure. Hypertension
      affects nearly 30% of the world's population; therefore, reducing blood pressure
      is key for the prevention of stroke. Unlike the established role of hypertension
      as a risk factor for stroke, the prognostic importance of blood pressure in
      determining outcome after acute stroke is unclear. The acute hypertensive
      response occurs in more than 50% of all patients with acute stroke and is
      associated with poor prognosis. The relation between the outcome of acute stroke
      and blood pressure is U-shaped, with the best outcome at systolic blood-pressure
      levels ranging from about 140 to 180 mm Hg. The evidence that decreasing blood
      pressure in hypertensive patients with acute ischaemic or haemorrhagic stroke
      improves prognosis needs further confirmation. Whether raising blood pressure to
      improve perfusion of ischaemic brain areas is beneficial remains even more
      uncertain. Present guidelines for the management of blood pressure in patients
      with acute stroke are not evidence-based, but results from ongoing trials might
      provide more informed recommendations for the future.

PMID- 19747656
TI  - Malignant middle cerebral artery infarction: clinical characteristics, treatment
      strategies, and future perspectives.
AB  - Space-occupying, malignant middle cerebral artery (MCA) infarctions are still one
      of the most devastating forms of ischaemic stroke, with a mortality of up to 80%
      in untreated patients. An early diagnosis is essential and depends on CT and MRI
      to aid the prediction of a malignant course. Several pharmacological strategies
      have been proposed but the efficacy of these approaches has not been supported by
      adequate evidence from clinical trials and, until recently, treatment of
      malignant MCA infarctions has been a major unmet need. Over the past 3 years,
      results from randomised controlled trials and their pooled analyses have provided
      evidence that an early hemicraniectomy leads to a substantial decrease in
      mortality at 6 and 12 months and is likely to improve functional outcome.
      Hemicraniectomy is now in routine use for the clinical management of malignant
      MCA infarction in patients younger than 60 years of age. However, there are still
      important questions about the individual indication for decompressive surgery,
      particularly with regard to the ideal timing of hemicraniectomy, a potential cut
      off age for the procedure, the hemisphere affected, and ethical considerations
      about functional outcome in surviving patients.

PMID- 19747657
TI  - Cervicogenic headache: an assessment of the evidence on clinical diagnosis,
      invasive tests, and treatment.
AB  - Cervicogenic headache is characterised by pain referred to the head from the
      cervical spine. Although the International Headache Society recognises this type
      of headache as a distinct disorder, some clinicians remain sceptical. Laboratory
      and clinical studies have shown that pain from upper cervical joints and muscles
      can be referred to the head. Clinical diagnostic criteria have not proved valid,
      but a cervical source of pain can be established by use of fluoroscopically
      guided, controlled, diagnostic nerve blocks. In this Review, we outline the basic
      science and clinical evidence for cervicogenic headache and indicate how opposing
      approaches to its definition and diagnosis affect the evidence for its clinical
      management. We provide recommendations that enable a pragmatic approach to the
      diagnosis and management of probable cervicogenic headache, as well as a rigorous
      approach to the diagnosis and management of definite cervical headache.

PMID- 19747658
TI  - Geotourism and volcanoes: health hazards facing tourists at volcanic and
      geothermal destinations.
AB  - Volcano tourism and tourism to geothermal destinations is increasingly popular.
      If such endeavors are to be a sustainable sector of the tourism industry,
      tourists must be made aware of the potential health hazards facing them in
      volcanic environments. With the aim of creating awareness amongst the tourism
      industry and practitioners of travel medicine, this paper reviews the potential
      influences and effects of volcanic gases such as carbon dioxide (CO(2)), hydrogen
      sulfide (H(2)S), sulfur dioxide (SO(2)), and hydrogen chloride/hydrochloric acid
      (HCl). It also reviews the negative health impacts of tephra and ash, lava flows,
      landslides, and mudflows. Finally, future research striving to quantify the
      health risks facing volcano tourists is recommended.

PMID- 19747659
TI  - Common ailments observed among students and their parents during travel.
AB  - BACKGROUND: Vast majority of Indians travel for religious, cultural and socio
      economic purposes either alone or with families. OBJECTIVES: The present study
      attempts to elicit the travel related health issues experienced by college
      students (youth) and their parents (elderly) during travel, to identify the
      variations between youth and elderly, and to suggest remedial measures. MATERIAL
      AND METHODS: A total of 400 college students (age range 17-25; mean age 21) and
      330 of their parents (age range 39-64; mean age 49) were included in the study.
      After a brief introduction to the study, a pretested structured anonymous
      questionnaire was distributed and completed. The data was analyzed statistically.
      RESULTS: Ailments were significantly (p<0.01) more prevalent among parents
      (elderly) than college students (youth) and were attributed to co-existing or
      exacerbation of pre-existing illnesses, stress of travel and waning immunity.
      None carried medical insurance or took pre-travel advice. Less than 21% of
      students and more than 70% of parents carried medicines for common ailments
      during travel. Also, parents carried personal protective materials significantly
      more than their wards. COMMENTS: A joint effort by health care professionals,
      travel agents, government and media towards community education may decrease the
      travel related ailments/illnesses.

PMID- 19747660
TI  - Early small bowel perforation and cochleovestibular impairment as rare
      complications of typhoid fever.
AB  - Two Indian migrant workers suffering from fever and malaise were admitted to the
      hospital directly after arrival in the Netherlands. The first patient was 25-year
      old man who had fever and rigors on admission. The patient was treated for
      presumptive typhoid fever with ciprofloxacin. Cefotaxime was added the following
      day because of the possibility of a nalidixic-acid resistant strain of S. typhi.
      The clinical course was complicated by a small bowel perforation on the third day
      of the disease. Blood cultures grew a nalidixic acid resistant strain of
      Salmonella enterica serovar typhi. The patient recovered completely. The second
      patient, a 22-year-old man, suffered from fever, malaise and hearing loss. A
      sensorineural hearing loss with vestibular dysfunction was diagnosed. Cultures of
      blood and bone marrow aspirate showed a nalidixic acid resistant strain of S.
      typhi. Treatment with ciprofloxacin and ceftazidime improved the hearing loss
      significantly. The clinical features of typhoid fever are heterogeneous and rare
      complications may occur. The emergence of multidrug and nalidixic acid resistance
      may complicate further the treatment of this serious systemic infection.

PMID- 19747661
TI  - Malaria zoonoses.
AB  - The genus Plasmodium includes many species that naturally cause malaria among
      apes and monkeys. The 2004 discovery of people infected by Plasmodium knowlesi in
      Malaysian Borneo alerted to the potential for non-human species of plasmodia to
      cause human morbidity and mortality. Subsequent work revealed what appears to be
      a surprisingly high risk of infection and relatively severe disease, including
      among travelers to Southeast Asia. The biology and medicine of this zoonosis is
      reviewed here, along with an examination of the spectrum of Plasmodium species
      that may cause infection of humans.

PMID- 19747662
TI  - A travel medicine view of dengue and dengue hemorrhagic fever.
AB  - Dengue fever is the most prevalent arboviral infection worldwide, with up to 40%
      of the world population living in endemic regions. Among travelers to tropical
      countries, dengue infection is increasingly reported, and it is now a leading
      cause of post-travel fever. Outbreaks of dengue-like illness were already
      described since the 18th century, but it is only in the last half century that a
      severe form of the disease - dengue hemorrhagic fever (DHF) has been described.
      Although the cause of DHF is not established, the prevailing theory attributes
      the disease to antibody-dependent enhancement of viral replication, in the
      presence of a secondary dengue infection. Comparative studies of primary vs.
      secondary infection are difficult to perform in endemic countries because of the
      rarity of primary infection except during early infancy. Travelers on the other
      hand are usually diagnosed with primary infection and are therefore a better
      study population. Data on dengue and DHF among travelers appears to suggest that
      severe dengue and DHF occur in similar rates among cases with primary and with
      secondary infections. Epidemiological and physiological data from travelers
      suggest that the prevailing theory on the causes of DHF needs to be reconsidered.

PMID- 19747663
TI  - Health and safety aspects of deployment of Australian disaster medical assistance
      team members: results of a national survey.
AB  - BACKGROUND: Disaster medical assistance teams (DMATs) have responded to numerous
      international disasters in recent years. As part of a national survey, the
      present study was designed to evaluate Australian DMAT experience in relation to
      health and safety aspects of actual deployment. METHODS: Data were collected via
      an anonymous mailed survey distributed by State and Territory representatives on
      the Australian Health Protection Committee, who identified team members
      associated with Australian DMAT deployments from the time of the 2004 South East
      Asian tsunami disaster. RESULTS: The response rate for this survey was 50%
      (59/118). Most of the personnel had deployed to the tsunami affected areas. The
      DMAT members were quite experienced with 53% of personnel in the 45-55 years age
      group (31/59) and a mean level of clinical experience of 21 years. 76% of the
      respondents were male (44/58). Once deployed, most felt that their basic health
      needs were adequately met. Almost all stated there were adequate shelter (95%,
      56/59), adequate food (93%, 55/59) and adequate water (97%, 57/59). A clear
      majority, felt there were adequate toilet facilities (80%, 47/59), adequate
      shower facilities (64%, 37/59); adequate hand washing facilities (68%, 40/59) and
      adequate personal protective equipment (69%, 41/59). While most felt that there
      were adequate security briefings (73%, 43/59), fewer felt that security itself
      was adequate (64%, 38/59). 30% (18/59) felt that team members could not be easily
      identified. The optimum shift period was identified as 12h (66%, 39/59) or
      possibly 8h (22%, 13/59) with the optimum period of overseas deployment as 14-21
      days (46%, 27/59). Missing essential items were just as likely to be related to
      personal comfort (28%) as clinical care (36%) or logistic support (36%). The most
      frequently nominated personal items recommended were: suitable clothes (49%,
      29/59); toiletries (36%, 22/59); mobile phone (24%, 14/59); insect repellent
      (17%, 10/59) and a camera (14%, 8/59). The most common personal hardship reported
      during their deployment was being away from home/problems at home (24%, 14/59);
      however, most felt that their family was adequately informed of their whereabouts
      and health status (73%, 43/59). CONCLUSIONS: This study of Australian DMAT
      members suggests that, in the field, attention should be given to basics, such as
      adequate food, water, shelter and personal hygiene as well as appropriate
      clothing, sunscreen and vector protection. The inclusion of appropriate personal
      items can be assisted by provision of a minimum suggested personal equipment
      list, with local conditions and the nature of the deployment being taken into
      account. A personal survival kit should also be recommended. There should be
      medical and psychological support for team members themselves, including the
      provision of a dedicated team member medical cache. Concern for their own health
      and ability to communicate with family members at home are major issues for
      deployed team members and need to be addressed in mission planning. This should
      also recognise security issues, including briefings, evacuation plans and exit
      strategies. The team members concerns about adequate security and the risk
      profile of humanitarian intervention in natural disasters compared with complex
      humanitarian emergencies may help determine future deployment of civilian or
      defence based teams.

PMID- 19747664
TI  - Travel patterns and health risks for patients infected with HIV.
AB  - International travelers are at increased risk of acquiring infectious diseases.
      These risks are even greater for individuals visiting resource-poor tropical
      regions and for immunocompromised travelers, including those with HIV infection.
      We reviewed ten years of consultative charts from the International Health Clinic
      at the Ottawa Hospital General Campus to describe travel risks and preventative
      measures for international travelers infected with HIV. A total of 100 patients
      infected with HIV (63 male, 37 female; mean age 42.2 years) were referred to the
      clinic prior to international travel. More than half (57%) were born in countries
      endemic for tropical diseases. Overall the median HIV viral load (VL) was <50
      copies/ml (i.e. undetectable) and the median CD4 count was 440 cells/microL
      (IQR=285-630). The most common destination regions were sub-Saharan Africa (55
      patients) and the Caribbean (14 patients). Endemic-born patients took longer
      trips than Canadian-born travelers (mean 45.2 vs. 22.7 days, p<0.05), were more
      likely to travel to visit friends and relatives (80.7% vs. 4.7%, p<0.05), and
      frequented regions with higher risks of malaria and other infectious tropical
      diseases. Endemic-born travelers infected with HIV stay abroad longer and are
      more likely to visit malarious regions than their Canadian-born counterparts.
      More research is needed to ensure the best preventive care of these special needs
      travelers.

PMID- 19747665
TI  - Travel-related health problems in Japanese travelers.
AB  - BACKGROUND: Although the number of Japanese individuals traveling abroad has
      increased steadily, reaching approximately 17.3 million in 2007, the incidence of
      various travel-related health problems in Japan remains unknown. The travel
      related health problems of Japanese travelers returning to Japan from abroad are
      analyzed by assessing the records. METHODS: Data were collected retrospectively
      on returning travelers who visited the authors' travel clinic during the period
      from January 2005 through to December 2006 with any health problem acquired
      overseas. A total of 345 patients were included in this study (200 male, 145
      female; average age, 34+/-12.3 years). RESULTS: Reasons for travel included
      leisure (45.8%); business (39.1%); visiting friends and relatives or accompanying
      other travelers (8.7%); volunteering (3.8%); and long stays in order to study or
      live (2.6%). The most visited destination was Asia (n=260), followed by Africa
      (n=105). The most commonly reported health problems were gastro-intestinal
      infections (39.1%), followed by respiratory tract infections (16.2%), animal
      bites (8.1%), and skin problems (5.8%). Together, malaria and dengue accounted
      for 10% of diagnoses in 125 febrile patients (36.2%). CONCLUSION: Although the
      profile of travel-related health problems in Japanese travelers is similar to
      that of Western travelers, the characteristics of travel were quite different.
      Therefore Japanese travel advice should be tailored to suit the Japanese
      traveler.

PMID- 19747666
TI  - A new inactivated Japanese encephalitis vaccine for adult travelers.
AB  - Current guidelines for Japanese encephalitis (JE) vaccine relate to an older
      mouse brain derived vaccine with an uncertain history of adverse events including
      delayed anaphylaxis. JE is widely distributed, including in urban areas.
      Underreporting is likely in many endemic countries, and atypical clinical forms
      exist. A new JE vaccine produced in Vero cells has become available, which
      appears equi-efficacious to the mouse brain derived vaccine. In development
      trials the new JE vaccine was as well tolerated as placebo. A review of existing
      guidelines for JE vaccine use in travelers should be considered.

PMID- 19747667
TI  - Pre- and post-deployment health support provided to Australian disaster medical
      assistance team members: results of a national survey.
AB  - BACKGROUND: Calls for disaster medical assistance teams (DMATs) are likely to
      continue in response to international disasters. As part of a national survey,
      the present study was designed to evaluate Australian DMAT experience in relation
      to pre- and post-deployment health care. METHODS: Data was collected via an
      anonymous mailed survey distributed via State and Territory representatives on
      the Australian Health Protection Committee, who identified team members
      associated with Australian DMAT deployments from the 2004 South East Asian
      Tsunami disaster. RESULTS: The response rate for this survey was estimated to be
      around 50% (59/118). Most of the personnel had deployed to the tsunami affected
      areas. The DMAT members were quite experienced with 53% of personnel in the 45-55
      years age group (31/59). Seventy-six percent of the respondents were male
      (44/58). Only 42% (25/59) received a medical check prior to departure and only
      15% (9/59) received a psychological assessment prior to deployment. Most
      respondents indicated that both medical and psychological screening of personnel
      would be desirable. Most DMAT personnel received some vaccinations (83%, 49/59)
      before departure and most felt that they were adequately immunised. While nearly
      all DMAT members participated in formal debriefing post-deployment (93%, 55/59),
      far less received psychological debriefing (44%, 26/59), or a medical examination
      upon return (10%, 6/59). Three respondents reported experiencing physical ill
      health resulting in time off work following their return. While only one
      reportedly experienced any adjustment problems post-deployment that needed time
      off work, 32% (19/59) found it somewhat difficult to return to work. There were
      multiple agencies involved in the post-deployment debriefing (formal and
      psychological) and medical examination process including Emergency Management
      Australia (EMA), Australian Government, State/Territory Health Departments,
      District Health services and others. CONCLUSIONS: This study of Australian DMAT
      members suggests that more emphasis should be placed on health of personnel prior
      to deployment with pre-deployment medical examinations and psychological
      assessment. Following the return home, and in addition to mission and
      psychological debriefing, there should be a post-deployment medical examination
      and ongoing support and follow-up of DMAT members. More research is needed to
      examine deployment health support issues.

PMID- 19747668
TI  - Pre-travel counselling in Greece for travellers visiting friends and relatives.
AB  - Pre-travel services are underused by travellers visiting friends and relatives
      (VFRs). The objective of this study was to define the proportion and the profile
      of VFRs who seek pre-travel counselling in Greece. The study was conducted
      prospectively, from July, 2005 to December, 2007, in seven Health Departments of
      the Prefectures in Athens and Attica, where 35.6% of the Greek population
      resides; migrants account for 17% and 8% of the population in these areas,
      respectively. 2548 travellers seeking pre-travel advice were studied; 23 (0.9%)
      were identified as VFRs. Children younger than 15 years accounted for 30.4% of
      VFRs, compared to 2.3% among non-VFRs. VFRs were younger than non-VFRs (mean
      ages: 29.9 versus 40.4 years, respectively). A comparison of VFRs with non-VFRs
      revealed that VFRs travelled for longer periods of time, stayed at local people's
      home more frequently (87% versus 15.5%), and travelled on an organized trip less
      frequently (4.3% versus 54.6%). Considering the fact that 36,056 VFRs travelled
      from Greece to Africa and Asia during 2005-2007, and that only 1 out of 700 VFRs
      to these destinations pre-travel advice in Greece, communication strategies to
      access efficiently this group of travellers should be explored urgently.

PMID- 19747669
TI  - Acinetobacter lwoffii: bacteremia associated with acute gastroenteritis.
AB  - Acinetobacter lwoffii is a non-fermentative aerobic gram-negative bacillus that
      is seen as a normal flora of the oropharynx and skin in approximately 25% of the
      healthy individuals. Due to its ubiquitous nature, it is a potential
      opportunistic pathogen in patients with impaired immune systems, and it has been
      identified as a cause of nosocomial infections like septicemia, pneumonia,
      meningitis, urinary tract infections, skin and wound infections. To our
      knowledge, this is the first case reported of a community acquired A. lwoffii
      bacteremia associated with gastroenteritis.

PMID- 19747670
TI  - Fibrous subcutaneous nodule caused by Dirofilaria repens.
AB  - A case is described of subcutaneous dirofilariasis in a Greek woman who had
      visited many countries around the world, including areas of sub-Saharan Africa.
      The patient presented with a single hard subcutaneous nodule on the right cheek,
      with no cutaneous manifestations of early or long-standing onchocercal dermatitis
      or eye lesions. The nodule was removed surgically and the filarial adult worm
      Onchocerca volvulus was initially diagnosed, based on the history, the hardness
      and large size of the fibrous nodule and the absence of cuticular longitudinal
      ridges of the parasite in the initial histological sections. Bloodless skin snips
      taken from the regions of the scapula, iliac crest and lateral calf were negative
      for O. volvulus microfilariae. Serial cross-sections of the fibrous nodule and
      gross examination of a portion of the adult worm removed from the nodule revealed
      the characteristic longitudinal ridges which allowed the identification of the
      worm as Dirofilaria repens. The aim of this report on tropical and non-tropical
      filarial worms affecting the skin and eyes is to point out the key features for
      precise identification of the parasites and differential diagnosis of the
      infections caused by the filiform nematode worms of O. volvulus, and Dirofilaria
      species.

PMID- 19747671
TI  - Trends in the publication of scientific research in travel medicine from Latin
      America.

PMID- 19747672
TI  - Tattoos and paucibacillary leprosy.

PMID- 19747673
TI  - Cost concern on hepatitis B virus screening for workers pursuing work aboard.

PMID- 19747674
TI  - Distinguishing the cause and consequence of face inversion: the perceptual field
      hypothesis.
AB  - I published a critical review of the face inversion effect (Rossion, 2008) that
      triggered a few reactions and commentaries by colleagues in the field
      (Riesenhuber & Wolff, 2009; Yovel, in press). Here, I summarize my original paper
      and attempt to identify the source of both the agreements and disagreements with
      my colleagues, as well as other authors, regarding the nature of the face
      inversion effect. My view is that the major cause of the detrimental effect of
      inversion on an observer's performance at individual face recognition is the
      disruption of a perceptual process. This perceptual process is makes and observer
      see the multiple features of a whole individual upright face at once. It also
      makes the percept of a given facial feature highly dependent on the location and
      identity of the other features in the whole face. The perceptual process is
      holistic because it is driven by a holistic face representation, derived from
      visual experience. Hence, an inverted face cannot be perceived holistically: the
      perceptual field of the observer is constricted for inverted faces, each facial
      feature having to be processed sequentially, independently, i.e. over a smaller
      spatial window than the whole face. Consequently, it is particularly difficult to
      perceive diagnostic cues that involve several elements over a wide space on an
      inverted face, such as long-range relative distances between features (e.g.,
      relative distance between eyes and mouth), or diagnostic cues that are located
      far away from usual gaze fixation (e.g., mouth-nose distance or mouth shape when
      fixating between the eyes). These difficulties are mere consequences of face
      inversion--the cause being a loss of holistic perception--, and it does not
      follow that relative distances between internal features are necessarily
      particularly important to recognize faces, that they should be labeled
      "configural", or should be given a specific status at the representational level.
      I argue that distinguishing the cause and consequence(s) of face inversion this
      way can provide a parsimonious and yet complete theoretical account of the face
      inversion effect.

PMID- 19747675
TI  - Quality control in the optical industry: From a work analysis of lens inspection
      to a training programme, an experimental case study.
AB  - A cognitive work analysis of quality inspection in the optical industry has been
      carried out in order to devise a training programme. The task concerned the
      inspection of high quality human eyeglass lenses. We conducted an experimental
      investigation of defect detection and acceptability decision-making tasks in 18
      experts and novice inspectors. Detection and decision-making were investigated
      together and separately in two experimental sessions. We showed the effect of
      expertise on reaction times and errors, and we described the cognitive processes
      of novice inspectors. On the basis of the processing differences between the two
      groups, a training programme for new inspectors was devised and described.
      Finally, training effects were tested.

PMID- 19747676
TI  - Hunting with lead: association between blood lead levels and wild game
      consumption.
AB  - BACKGROUND: Wild game hunting is a popular activity in many regions of the United
      States. Recently, the presence of lead fragments in wild game meat, presumably
      from the bullets or shot used for hunting, has raised concerns about health risks
      from meat consumption. OBJECTIVE: This study examined the association between
      blood lead levels (PbB) and wild game consumption. METHODS: We recruited 742
      participants, aged 2-92 years, from six North Dakota cities. Blood lead samples
      were collected from 736 persons. Information on socio-demographic background,
      housing, lead exposure source, and types of wild game consumption (i.e., venison,
      other game such as moose, birds) was also collected. Generalized estimating
      equations (GEE) were used to determine the association between PbB and wild game
      consumption. RESULTS: Most participants reported consuming wild game (80.8%)
      obtained from hunting (98.8%). The geometric mean PbB were 1.27 and 0.84
      microg/dl among persons who did and did not consume wild game, respectively.
      After adjusting for potential confounders, persons who consumed wild game had
      0.30 microg/dl (95% confidence interval: 0.16-0.44 microg/dl) higher PbB than
      persons who did not. For all game types, recent (<1 month) wild game consumption
      was associated with higher PbB. PbB was also higher among those who consumed a
      larger serving size (> or = 2 oz vs. <2 oz); however, this association was
      significant for 'other game' consumption only. CONCLUSIONS: Participants who
      consumed wild game had higher PbB than those who did not consume wild game.
      Careful review of butchering practices and monitoring of meat-packing processes
      may decrease lead exposure from wild game consumption.

PMID- 19747677
TI  - Adaptive backstepping fault-tolerant control for flexible spacecraft with unknown
      bounded disturbances and actuator failures.
AB  - In this paper, a robust adaptive fault-tolerant control approach to attitude
      tracking of flexible spacecraft is proposed for use in situations when there are
      reaction wheel/actuator failures, persistent bounded disturbances and unknown
      inertia parameter uncertainties. The controller is designed based on an adaptive
      backstepping sliding mode control scheme, and a sufficient condition under which
      this control law can render the system semi-globally input-to-state stable is
      also provided such that the closed-loop system is robust with respect to any
      disturbance within a quantifiable restriction on the amplitude, as well as the
      set of initial conditions, if the control gains are designed appropriately.
      Moreover, in the design, the control law does not need a fault detection and
      isolation mechanism even if the failure time instants, patterns and values on
      actuator failures are also unknown for the designers, as motivated from a
      practical spacecraft control application. In addition to detailed derivations of
      the new controller design and a rigorous sketch of all the associated stability
      and attitude error convergence proofs, illustrative simulation results of an
      application to flexible spacecraft show that high precise attitude control and
      vibration suppression are successfully achieved using various scenarios of
      controlling effective failures.

PMID- 19747678
TI  - Holding power of variable pitch screws in osteoporotic, osteopenic and normal
      bone: are all screws created equal?
AB  - INTRODUCTION: Biomechanical properties of four different commercially available
      small fragment cannulated screws (Twin fix (Stryker, Freiburg, Germany), Herbert,
      (Zimmer, Warsaw, USA), Omnitech (Unimedical, Torino, Italy), Barouk (Depuy,
      Warsaw, USA)), with variable pitch, used for fracture fixation were compared.
      MATERIALS AND METHODS: Polyurethane foam blocks of three different densities with
      mechanical properties similar to osteoporotic, osteopenic and normal bones were
      used to conduct the tests. Each screw was tested for pushout and pullout holding
      power after a primary insertion and for pullout after a repeated insertion into
      the respective foam blocks. RESULTS: The mean pullout and pushout strengths of
      all screws correlated to the foam density, and were significantly (p<0.001 and
      <0.001, respectively) better in foam with higher density. The mean pullout
      strength of each screw was consistently lower after reinsertion into the
      osteoporotic, osteopenic and normal bone densities by 4-30%, when compared to the
      index insertion (Fig. 4b). Yet, this difference was not found to be statistically
      significant (p=0.23). The Barouk screw performed significantly (p<0.0001) better
      than the other screws in all three different densities of foam for both for
      pushout and pullout after index insertion as well as for pullout tests after
      reinsertion. CONCLUSION: The holding power of screws is directly correlated to
      bone density, thread design and number of threads engaging the bone. Reinsertion
      through the same hole could reduce the ultimate pullout strength. The surgeon
      should consider the advantages and disadvantages of each implant, depending on
      the clinical situation and choose accordingly.

PMID- 19747679
TI  - Comparison of four perioperative misoprostol regimens for surgical termination of
      first-trimester pregnancy.
AB  - OBJECTIVE: To compare the outcomes of 4 different perioperative misoprostol
      regimens for surgical termination of first-trimester pregnancy. METHODS:
      Retrospective analysis of the records of 4000 women (4 cohorts of 1000 each) who
      underwent surgical termination of pregnancy. The 4 cohorts received: no
      misoprostol; 200 microg of oral misoprostol 30 minutes preoperatively; 200 microg
      of sublingual misoprostol 30 minutes preoperatively; or 200 microg of oral
      misoprostol 3 hours preoperatively plus 200 microg of vaginal misoprostol
      postoperatively. Adverse effects of the last regimen were surveyed in 1000 women.
      RESULTS: In the cohorts that received misoprostol, the difficulty of cervical
      dilatation was reduced (P<0.001) compared with the cohort of women that did not
      receive misoprostol. The frequency with which women made postoperative contacts
      with the clinic was also reduced in the cohorts that received misoprostol
      (P<0.05). Adverse effects were minimal. CONCLUSIONS: This retrospective study
      showed an association between perioperative administration of misoprostol,
      reduced difficulty for operators, and reduced demand for postoperative care. The
      regimen associated with the greatest reduction in difficult cervical dilatations
      and postoperative consultations was 200 microg of oral misoprostol 3 hours
      preoperatively plus 200 microg of misoprostol vaginally at the end of the
      surgical procedure.

PMID- 19747680
TI  - Oxidized low-density lipoprotein (Ox-LDL) impacts on erythrocyte viscoelasticity
      and its molecular mechanism.
AB  - The oxidized low-density lipoprotein (Ox-LDL) plays an important role in
      atherosclerosis, yet it remains unclear if it damages circulating erythrocytes.
      In this study, erythrocyte deformability and its membrane proteins after Ox-LDL
      incubations are investigated by micropipette aspiration, thiol radical
      measurement, and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS
      PAGE). Results show that Ox-LDL incubation reduces the erythrocyte deformability,
      decreases free thiol radical contents in erythrocytes, and induces the cross
      linking among membrane proteins. SDS-PAGE analysis reveals a high molecular
      weight (HMW) complex as well as new bands between spectrins and band 3 and
      reduced ratios between band 3 and other major membrane skeletal proteins.
      Analyses indicate that Ox-LDL makes erythrocytes harder to deform through a
      molecular mechanism by which the oxidation of free thiol radicals forms disulfide
      bonds among membrane skeletal proteins.

PMID- 19747681
TI  - Application of liquid chromatography-tandem mass spectrometry for the
      characterization of galactosylated and tagatosylated beta-lactoglobulin peptides
      derived from in vitro gastrointestinal digestion.
AB  - This article describes a comprehensive characterization of bovine beta
      lactoglobulin peptides glycated with an aldohexose (galactose) or a ketohexose
      (tagatose), derived from in vitro gastrointestinal digestion, by liquid
      chromatography coupled to positive electrospray ion trap tandem mass
      spectrometry. In addition to the dissociation pathway previously described for
      aldohexoses-derived Amadori compounds, i.e. formation of the pyrylium ([M+H](+)
      54) and furylium ions ([M+H](+)-84) via the oxonium ion ([M+H](+)-18), another
      and more direct fragmentation route involving the formation of the imminium ion
      ([M+H](+)-150) is also reported following extensive glycation rates of beta
      lactoglobulin with both carbohydrates. These results indicated that the analysis
      of digested proteins by LC-ESI-MS(2) on a three-dimensional ion trap monitoring
      neutral losses is an efficient and direct method to identify peptides glycated
      not only through the Amadori rearrangement but also via the Heyns rearrangement.
      Nevertheless, as the predominating MS(2) fragmentation pattern of the glycated
      peptides is derived from the sugar moiety, the sequence-informative b- and y-ions
      resulting from peptide backbone cleavage were undetected. To overcome this
      drawback, and taking advantage of multi-stage fragmentation capabilities of ion
      traps, the indicative Amadori and Heyns-derived imminium ions were successfully
      used in MS(3) analyses to identify the peptide backbone, as well as the specific
      glycation site. In addition, further MS(4) analyses were needed to carry out the
      characterization of doubly glycated peptides.

PMID- 19747682
TI  - Selecting a suitable method for residue analysis will depend on the problem at
      hand as well as on the final goal. Foreword.

PMID- 19747683
TI  - Quantitative structure-retention relationship studies for taxanes including
      epimers and isomeric metabolites in ultra fast liquid chromatography.
AB  - Seven pairs of epimers and one pair of isomeric metabolites of taxanes, each pair
      of which have similar structures but different retention behaviors, together with
      additional 13 taxanes with different substitutions were chosen to investigate the
      quantitative structure-retention relationship (QSRR) of taxanes in ultra fast
      liquid chromatography (UFLC). Monte Carlo variable selection (MCVS) method was
      adopted to choose descriptors. The selected four descriptors were used to build
      QSRR model with multi-linear regression (MLR) and artificial neural network (ANN)
      modeling techniques. Both linear and nonlinear models show good predictive
      ability, of which ANN model was better with the determination coefficient R(2)
      for training, validation and test set being 0.9892, 0.9747 and 0.9840,
      respectively. The results of 100 times' leave-12-out cross validation showed the
      robustness of this model. All the isomers can be correctly differentiated by this
      model. According to the selected descriptors, the three dimensional structural
      information was critical for recognition of epimers. Hydrophobic interaction was
      the uppermost factor for retention in UFLC. Molecules' polarizability and
      polarity properties were also closely correlated with retention behaviors. This
      QSRR model will be useful for separation and identification of taxanes including
      epimers and metabolites from botanical or biological samples.

PMID- 19747684
TI  - Inverse gas chromatography as a technique for the characterization of the
      performance of Mn/Zr mixed oxides as combustion catalysts.
AB  - Adsorption of different volatile organic compounds (trichloroethylene, TCE; 1,2
      dichloroethane, DCE; n-hexane) over different manganese-zirconia mixed oxides
      (Mn(x)Zr(1-x)O(2)) - widely used as combustion catalysts - was studied by inverse
      gas chromatography. Adsorption isotherms (calculated in the Henry region),
      adsorption enthalpies (DeltaH(ads)), and dispersive (gamma(S)(D)) and specific
      (I(sp)) components of the surface energy have been determined at infinite
      dilution for the investigated compounds. Both the adsorption enthalpy and the
      specificity of the interaction of TCE and DCE over Mn(x)Zr(1-x)O(2) catalysts
      depend strongly on manganese content. Thus, the adsorption strength of the
      reactants over the active sites is closely related with both the surface acidity
      and the accessibility of the lattice oxygen. A great influence of the specific
      interaction on the catalytic pattern has been also noticed. Since I(sp) depends
      on the redox properties, it has been proved that the specific interaction is
      determined by the presence of bulk Mn(3)O(4), which hinders the mobility of the
      oxygen lattice, and MnO(x), with the contrary effect. Finally, the selectivity to
      oxidation products has been correlated with both the enthalpy of adsorption and
      the specific interaction parameter, decreasing the selectivity to HCl with the
      increase of the enthalpy of adsorption.

PMID- 19747685
TI  - High performance liquid chromatography coupled to an optical fiber detector
      coated with laccase for screening catecholamines in plasma and urine.
AB  - An analytical method based on separation by high performance liquid
      chromatography (HPLC) and detection by optical fiber (OF) coated with an enzyme
      (laccase), has been developed for separation and quantification of
      catecholamines, namely epinephrine, dopamine and norepinephrine. The application
      of OF as a detector in this analytical system relies on the variation of the
      reflected optical power detected when the catecholamines eluted from the HPLC
      column act as the substrate of the laccase immobilized on a tip of a single-mode
      OF. The developed method shows a high linearity in a range between 5 and 125
      pg/mL and detection limits of 3.5, 2.9 and 3.3 pg/mL for epinephrine, dopamine
      and norepinephrine, respectively. The analytical performance of the proposed
      method was compared with a classical analytical method, namely high performance
      liquid chromatography-electrochemical detector (HPLC-ED) regarding catecholamines
      detection, showing great analytical advantages such as low cost of equipment.
      Additionally, the proposed method was applied to catecholamines determination in
      actual samples of plasma and human urine.

PMID- 19747686
TI  - 23rd International Symposium on Microscale Bioseparations. Foreword.

PMID- 19747687
TI  - Improved separation of furocoumarins of essential oils by supercritical fluid
      chromatography.
AB  - Separation of furocoumarins has become of a great interest for cosmetic industry
      and human health, since the recent directive of the European Union. Furocoumarins
      are a class of compounds presenting varied substituents linked mainly in two
      positions to an identical skeleton made by a furan ring bonded to a coumarin
      nucleus (Psoralen). The substituents are mainly methoxy, or alkyl chains, which
      can contain double bonds, hydroxyl or epoxy groups. Due to the variety of
      compounds, and their subtle structure differences, their separation requires high
      performance methods. Multi-gradient high-performance liquid chromatography (HPLC)
      and two-dimensional chromatography are usually applied. This paper describes a
      new approach, by using super/subcritical fluid chromatography (SFC), with a green
      mobile phase: CO(2)-ethanol. The choice of the stationary phase from varied types
      of phases, and the effects of numerous analytical parameters (flow rate, modifier
      percentage, temperature and outlet pressure) are studied, described and
      discussed, on the basis of the separation of a complex sample: lemon residue.
      From these studies, isocratic conditions are determined to obtain a satisfactory
      separation in 10 min. A two-dimensional analysis was also investigated, by
      performing first a class fractionation of compounds on an ethylpyridine (EP)
      phase, then by separating each class on a pentafluorophenyl phase (Discovery HS
      F5) with the selected isocratic mobile phase. A gradient elution is also studied
      to improve separation of some minor compounds. Structure of the eluted compounds
      was determined by comparison with standards, HPLC-DAD, HPLC-MS analysis, and NMR
      analysis of collected fractions. All these approaches allow relating structure of
      compounds to retention behaviour, which is unusual due to the selected
      pentafluorophenyl stationary phase.

PMID- 19747688
TI  - Capillary liquid chromatography using a hydrophilic/cation-exchange monolithic
      column with a dynamically modified cationic surfactant.
AB  - A novel form of reversed-phase liquid chromatography (RPLC) by the dynamically
      modified hydrophilic interaction monolithic column has been described in this
      paper. A porous poly(SPMA-co-PETA) monolith with strong cation-exchange (SCX) was
      prepared and the resulting monolith showed a typical hydrophilic interaction
      chromatography (HILIC) mechanism at higher organic solvent content (ACN%>50%).
      The good selectivity for neutral, basic and acidic polar analytes was observed in
      the HILIC mode. In order to increase the hydrophobic interaction, the monolith
      with SCX was dynamically modified with a long-chain quaternary ammonium salt,
      cetyltrimethylammonium bromide (CTAB), which was added to the mobile phase. CTAB
      ions were adsorbed onto the surface of the SCX monolithic material, and the
      resulting hydrophobic layer was used as the stationary phase. Using the
      dynamically modified SCX monolithic column, neutral, basic and acidic hydrophobic
      analytes were well separated with the RPLC mode.

PMID- 19747689
TI  - Ultra-high-performance liquid chromatography-tandem mass spectrometry for
      determining the presence of eleven personal care products in surface and
      wastewaters.
AB  - Personal care products (PCPs) are widely used emerging contaminants which can
      cause adverse environmental effects. This paper reports the development and
      validation of a method based on solid-phase extraction (SPE) and ultra-high
      performance liquid chromatography-electrospray ionisation-tandem mass
      spectrometry (UHPLC-(ESI)MS-MS) for simultaneously determining eleven PCPs: 4
      preservatives (methylparaben; ethylparaben; benzylparaben; propylparaben); 2
      antimicrobial agents (triclocarban and triclosan) and 5 UV filters (2,4
      dihydroxybenzophenone; 2,2-dihydroxy-4-methoxybenzophenone; benzophenone-3;
      octocrylene and octyldimethyl-p-aminobenzoic acid) in environmental waters in
      only 9 run minutes of chromatographic separation. The SPE was carried out with
      two polymeric cartridges (Oasis HLB and Bond Elut Plexa). The recoveries obtained
      with Bond Elut Plexa were between 69% and 101% for 500 mL of river waters, with
      the exception of octyldimethyl-p-aminobenzoic acid (46%). Limits of detection for
      500 mL of river water were in the range of 1-5 ng/L. Oasis HLB was chosen for
      wastewater samples with recoveries between 38% and 92% (250 mL of effluents) and
      36-89% (100mL of influents). In both wastewater samples, octyldimethyl-p
      aminobenzoic acid and methylparaben showed the lowest recoveries (20% and 27%).
      The method revealed benzophenone-3 as having the highest concentration levels ( 7
      ng/L) in river waters. Most of PCPs determined were found in influent waters
      being methylparaben and propylparaben the ones found at highest concentration
      with values of 5613 and 1945 ng/L, respectively. In effluent waters, significant
      lower levels of some PCPs were found, being benzophenone-3 the one found at the
      highest concentration (100 ng/L).

PMID- 19747690
TI  - Surface dilatational rheology measurements for oil/water systems with viscous
      oils.
AB  - This work presents an application of the capillary pressure tensiometry (CPT) for
      accurate measurements of the surface dilatational elastic and loss moduli of the
      interface between water and transparent oil phases with viscosities up to
      10,000mPas. Surface rheological studies involving viscous oils are not possible
      with other available methods due to the considerable bulk viscous forces.
      Theoretical estimations show that successful measurements with such systems are
      possible by using a suitable frequency range of the oscillating spherical drop
      method by CPT. Measurements with oils having viscosities between 5 and 10,000mPas
      at a frequency smaller than 1Hz were performed using the oil as outer phase and
      the aqueous surfactant solution as inner (drop) phase. As predicted by the theory
      the measured surface elastic modulus did not depend on the viscosity (within
      experimental accuracy). Three different approaches to account for the
      contribution of the bulk shear viscosity to the measured pressure signal were
      analyzed and applied. The results showed that if exact numerical corrections are
      used the calculated loss modulus also did not depend on the viscosities of the
      bulk phases. The two other methods used lead to errors, sometimes significant.

PMID- 19747691
TI  - Lipid microspheres loaded with antigenic membrane proteins of the Leishmania
      amazonensis as a potential biotechnology application.
AB  - Lipid microspheres (LM) are excellent drug delivery or vaccines adjuvant systems
      and are relatively stable. The aim of this work is to develop and characterize a
      system that is able to encapsulate and present antigenic membrane proteins from
      Leishmania amazonensis. Membrane proteins are important for vaccine's formulation
      because these proteins come in contact with the host cell first, triggering the
      cell mediated immune response. This is a useful tool to avoid or inactivate the
      parasite invasion. The LM are constituted by soybean oil (SO),
      dipalmitoylphosphatidilcholine (DPPC), cholesterol and solubilized protein
      extract (SPE). The particles formed presented an average diameter of 200 nm, low
      polydispersion and good stability for a period of 30 days, according to dynamic
      light scattering assays. Isopycnic density gradient centrifugation of LM-protein
      showed that proteins and lipids floated in the sucrose gradient (5-50%w/v)
      suggesting that the LM-protein preparation was homogeneous and that the proteins
      are interacting with the system. The results show that 85% of SPE proteins were
      encapsulated in the LM. Studies of cellular viability of murine peritoneal
      macrophages show that our system does not present cytotoxic effect for the
      macrophages and still stimulates their NO production (which makes its application
      as a vaccine adjuvant possible). LM-protein loaded with antigenic membrane
      proteins from L. amazonensis seems to be a promising vaccine system for
      immunization against leishmaniasis.

PMID- 19747692
TI  - The development of automatic associative processes and children's false memories.
AB  - We investigated children's ability to generate associations and how automaticity
      of associative activation unfolds developmentally. Children generated associative
      responses using a single associate paradigm (Experiment 1) or a Deese/Roediger
      McDermott (DRM)-like multiple associates paradigm (Experiment 2). The results
      indicated that children's ability to generate meaningful word associates, and the
      automaticity with which they were generated, increased between 5, 7, and 11 years
      of age. These findings suggest that children's domain-specific knowledge base and
      the associative connections among related concepts are present and continue to
      develop from a very early age. Moreover, there is an increase in how these
      concepts are automatically activated with age, something that results from domain
      general developments in speed of processing. These changes are consistent with
      the neurodevelopmental literature and together may provide a more complete
      explanation of the development of memory illusions.

PMID- 19747693
TI  - The impact of treatment on HPA axis activity in unipolar major depression.
AB  - Dysregulation of hypothalamic-pituitary-adrenal axis activity in major depressive
      disorder has been found to normalize with successful treatment, though
      inconsistencies exist. To determine the magnitude of change in cortisol levels
      from pre to post-treatment in individuals with unipolar depression quantitative
      methods of meta-analysis were applied. Thirty-four studies met inclusion criteria
      and consisted of a total of 1049 depressed patients across study samples. The
      overall mean effect size of pre-post-treatment cortisol measures indicated that
      approximately 56% of depressed participants had similar cortisol levels before
      and after treatment regardless of symptom improvement. The mean effect size of
      pre-post cortisol measures for those who responded to treatment was larger than
      the mean effect size of non-responders; however, this difference did not reach
      statistical significance. As well, no significant differences in mean effect size
      of pre-post cortisol measures based on type of treatment (e.g. antidepressant vs.
      ECT) were found. Subtype of depressive illness and length of treatment may
      contribute to the magnitude of change in cortisol measure before and after
      treatment. Inconsistent findings within the reviewed literature may confound the
      overall results. The type of treatment and response to treatment do not appear to
      impact the magnitude of change in cortisol level pre to post-treatment. Our
      findings suggest that the utility of cortisol as an outcome measure may be
      limited to specific subsets of the depressed population, and that given the
      variability in HPA results between studies, it is premature to state that
      cortisol is not a good outcome measure.

PMID- 19747694
TI  - Affect in Parkinson's disease: validation of the two-factor approach.
AB  - Depression in Idiopathic Parkinson's disease (IPD) is frequent, difficult to
      recognize, under managed and has a profound impact on quality of life. Current
      categorization of diagnosis in psychiatry poorly applies to the protean
      manifestations of mood disorders presented by parkinsonian patients. In this
      study we have chosen to dissect the state of depressive mood as assessed with the
      Beck Depression Inventory (BDI) at different points in time of pharmacological
      interventions using a dimensional approach. The 21 items of the BDI were
      classified in two new categories or factors: hyperkinetic and hypokinetic. The
      hyperkinetic factor included all items related to unbalanced intrusions of
      negative feelings and ideas, as well as to behavioral hyperactivity. The
      hypokinetic factor included all items related to loss of drive for appetitive
      behaviors and loss of mental and physical energy. The objectives were to (1)
      compare different pharmacological treatments on the two-factor approach in PD
      depression, (2) determine the influence of levodopa therapy on the two-factor
      approach, and (3) explore the two-factor approach in placebo conditions. Three
      sets of analyses using the hypo/hyperkinetic dichotomy favour a neurobiological
      dissociation of these factors in response to pharmacological intervention:
      symptoms of the hyperkinetic factor are responsive to serotonergic drugs while
      those of the hypokinetic one are not and may even show deterioration under SSRIs.
      In contrast, the hypokinetic factor is responsive to dopaminergic drugs and may
      show deterioration under serotonergic drugs. Furthermore, the two factors seem to
      transiently dissociate on placebo intervention aiming at correcting either mood
      or motor status. The dimensional approach to depression symptomatology may thus
      be of heuristic value in probing aminergic modulation of mood in IPD and
      establishing new correlations between affective and motor symptoms.

PMID- 19747695
TI  - Nonmotor fluctuations in Parkinson's disease: clinical spectrum and
      classification.
AB  - The majority of patients with Parkinson's disease (PD) on levodopa (LD) treatment
      usually experience motor fluctuations (MFs) within several years of initiation of
      treatment. Besides the classic MFs, many nonmotor fluctuations (NMFs) may occur
      in PD. NMFs appear both in the "on" state and "off" state. However, the clinical
      spectrum and the frequency of these symptoms are not well recognized. NMFs are
      usually mild and less disabling than MFs but sometimes can lead to unnecessary
      tests and therapies. NMFs occurring in association with the "on" state are better
      known and therefore more frequently diagnosed than those occurring in the "off"
      state. NMFs can be classified into three groups: autonomic,
      cognitive/psychiatric, and sensory. They include gastrointestinal and urinary
      symptoms, drenching sweats, temperature and blood-pressure changes, depression,
      anxiety, hallucinations, hypomania, moaning/screaming, confusion, cognitive
      dysfunction, sexual deviations and dopamine dysregulation syndrome (DDS), pain,
      akathisia, internal tremor, numbness/parasthesia, and dyspnea. CONCLUSION:
      Recognition of NMFs may prevent unnecessary diagnostic tests and may lead to
      treatment modifications aimed to minimize their occurrence.

PMID- 19747697
TI  - Mitral annular hinge motion contribution to changes in mitral septal-lateral
      dimension and annular area.
AB  - OBJECTIVE: The mitral annulus is a dynamic, saddle-shaped structure consisting of
      fibrous and muscular regions. Normal physiologic mechanisms of annular motion are
      incompletely understood, and more complete characterization is needed to provide
      rational basis for annuloplasty ring design and to enhance clinical outcomes.
      METHODS: Seventeen sheep had radiopaque markers implanted; 16 around the annulus
      and 2 on middle anterior and posterior leaflet edges. Four-dimensional marker
      coordinates were acquired with biplanar videofluoroscopy at 60 Hz. Hinge angle
      was quantified between fibrous and muscular annular planes, with 0 degrees
      defined at end diastole, to characterize its contribution to alterations in
      mitral septal-lateral dimension and 2-dimensional total annular area throughout
      the cardiac cycle. RESULTS: During isovolumic contraction (pre-ejection), hinge
      angle abruptly increased, reaching maximum (steepest saddle shape, change 18
      degrees +/- 13 degrees ) at peak left ventricular pressure. During ejection,
      hinge angle did not change; it then decreased during early filling (change 2
      degrees +/- 2 degrees ). Septal-lateral dimension and total area paralleled hinge
      angle dynamics and leaflet distance (anterior to posterior marker). Pre-ejection
      septal-lateral reduction was 13% +/- 7% (3.3 +/- 1.5 mm) from 9% muscular
      dimension fall and 18 degrees +/- 13 degrees hinge angle increase. CONCLUSIONS:
      Pre-ejection increase in hinge angle contributes substantially to septal-lateral
      and total area reduction, facilitating leaflet coaptation. Semirigid annuloplasty
      rings or partial bands may preserve hinge motion, but possible recurrent annular
      dilatation could result in recurrent mitral regurgitation. Long-term clinical
      studies are required to determine who might benefit most from preserving
      intrinsic hinge motion without compromising repair durability.

PMID- 19747698
TI  - Mechanistic aspects of CYP74 allene oxide synthases and related cytochrome P450
      enzymes.
AB  - The existence of CYP5, CYP8A, and the CYP74 enzymes specialized for reaction with
      fatty acid peroxide substrates presents opportunities for a "different look" at
      the catalytic cycle of the cytochrome P450s. This review considers how the
      properties of the peroxide-metabolizing enzymes are distinctive, and how they tie
      in with those of the conventional monooxygenase enzymes. Some unusual reactions
      of each class have parallels in the other. As enzyme reactions and P450
      structures emerge there will be possibilities for finding their special
      properties and edging this knowledge into the big picture.

PMID- 19747699
TI  - Oxidative burst inhibitory and cytotoxic amides and lignans from the stem bark of
      Fagara heitzii (Rutaceae).
AB  - Two amides, heitziamide A and heitziamide B and two phenylethanoids,
      heitziethanoid A and heitziethanoid B together with thirteen known compounds were
      isolated from F. heitzii (Letouzey). The structures of all compounds were
      established by spectroscopic analysis. Nine compounds were evaluated for
      oxidative burst inhibitory activity in a chemoluminescence assay and for
      cytotoxicity against PC-3 prostate cancer cells. All compounds exhibited a clear
      suppressive effect on phagocytosis response upon activation with serum opsonized
      zymosan at the range of IC(50)=2.0-6.5 microM, but no cytotoxic effect was
      observed (IC(50)>100 microM).

PMID- 19747700
TI  - Differing mechanisms of simple nitrile formation on glucosinolate degradation in
      Lepidium sativum and Nasturtium officinale seeds.
AB  - Glucosinolates are sulphur-containing glycosides found in brassicaceous plants
      that can be hydrolysed enzymatically by plant myrosinase or non-enzymatically to
      form primarily isothiocyanates and/or simple nitriles. From a human health
      perspective, isothiocyanates are quite important because they are major inducers
      of carcinogen-detoxifying enzymes. Two of the most potent inducers are benzyl
      isothiocyanate (BITC) present in garden cress (Lepidium sativum), and phenylethyl
      isothiocyanate (PEITC) present in watercress (Nasturtium officinale). Previous
      studies on these salad crops have indicated that significant amounts of simple
      nitriles are produced at the expense of the isothiocyanates. These studies also
      suggested that nitrile formation may occur by different pathways: (1) under the
      control of specifier protein in garden cress and (2) by an unspecified, non
      enzymatic path in watercress. In an effort to understand more about the
      mechanisms involved in simple nitrile formation in these species, we analysed
      their seeds for specifier protein and myrosinase activities, endogenous iron
      content and glucosinolate degradation products after addition of different iron
      species, specific chelators and various heat treatments. We confirmed that simple
      nitrile formation was predominantly under specifier protein control (thiocyanate
      forming protein) in garden cress seeds. Limited thermal degradation of the major
      glucosinolate, glucotropaeolin (benzyl glucosinolate), occurred when seed
      material was heated to >120 degrees C. In the watercress seeds, however, we show
      for the first time that gluconasturtiin (phenylethyl glucosinolate) undergoes a
      non-enzymatic, iron-dependent degradation to a simple nitrile. On heating the
      seeds to 120 degrees C or greater, thermal degradation of this heat-labile
      glucosinolate increased simple nitrile levels many fold.

PMID- 19747701
TI  - Hemiterpene glucosides and other constituents from Spiraea canescens.
AB  - Five glycosides, 2-(trans-cinnamoyloxy-methyl)-1-butene-4-O-beta-D
      glucopyranoside (1), 4-(6'-O-trans-cinnamoyl)-(2-hydroxymethyl-4-hydroxy-butenyl
      beta-D-glucopyranoside (2), 6''-O-trans-p-coumaroyl-(4-hydroxybenzoyl)-beta-D
      glucopyranoside (3), 6'-O-(4-methoxy-trans-cinnamoyl) alpha/beta-D-glucopyranose
      (4) 6'-O-(4''-methoxy-trans-cinnamoyl)-kaempferol-3-beta-D-glucopyranoside (7)
      along with six known compounds, (+)-isolariciresinol 3a-O-beta-D-glucopyranoside
      (8) (+)-lyoniresinol 3a-O-beta-D-glucopyranoside (9), apigenin 7-O-beta-D
      glucopyranoside (10), quercetin 3-O-beta-D-glucopyranoside (11), 6'-O-cinnamoyl
      alpha/beta-D-glucopyranose (6) 6'-O-p-coumaroyl-alpha/beta-D-glucopyranose (5)
      were isolated from the whole plant of Spiraea canescens. Some of these compounds
      showed potent radical scavenging activity in relevant non-physiological assays.
      Their structures were determined by NMR spectroscopic and CID mass spectrometric
      techniques.

PMID- 19747702
TI  - A comparison of citrus blossom volatiles.
AB  - The objective of this study was to identify the major volatiles and their
      relative concentrations in intact grapefruit, sweet orange, sour orange,
      mandarin, lemon, lime and pummelo blossoms. Volatiles from freshly picked
      blossoms were collected and concentrated using static headspace solid-phase
      microextraction and then separated and identified using GC-MS. Seventy volatiles
      were detected, 66 identified, of which 29 were identified for the first time in
      citrus blossoms. Major volatiles consisted of linalool, beta-myrcene, alpha
      myrcene, limonene, (E)-ocimene, methyl anthranilate and indole. In terms of total
      volatiles: pummelo >> grapefruit approximately = sweet orange > sour orange
      approximately = mandarin approximately = lemon-lime > Volkamer lemon > Kaffir
      lime. Principal component analysis of blossom volatiles demonstrated that there
      were three widely separated, tightly clustered groups which consisted of
      mandarin, lemon-lime and pummelo. Other cultivars of possible mixed parentage
      produced non-overlapping values within the boundaries of these three clustered
      groups. The first two Eigenvectors explained 83% of the total variance. Linalool,
      limonene and myrcene had the highest loading values. Those cultivars requiring
      insect pollination such as pummelo produced highest levels of total volatiles as
      well as highest levels of known honeybee stimulants such as 1-hexanol and
      linalool.

PMID- 19747703
TI  - Risk communication and management in public health crises.

PMID- 19747704
TI  - Food consumption patterns among adolescent and young adult smokers.

PMID- 19747705
TI  - Direct imaging of the disruption of hepatitis C virus replication complexes by
      inhibitors of lipid metabolism.
AB  - Here we have simultaneously characterized the influence of inhibitors of
      peroxisome proliferator-activated receptor alpha (PPARalpha) and the mevalonate
      pathway on hepatocyte lipid metabolism and the subcellular localization of
      hepatitis C virus (HCV) RNA using two-photon fluorescence (TPF) and coherent anti
      Stokes Raman scattering (CARS) microscopy. Using this approach, we demonstrate
      that modulators of PPARalpha signaling rapidly cause the dispersion of HCV RNA
      from replication sites and simultaneously induce lipid storage and increases in
      lipid droplet size. We demonstrate that reductions in the levels of cholesterol
      resulting from inhibition of the mevalonate pathway upregulates triglyceride
      levels. We also show that the rate of dispersion of HCV RNA is very rapid when
      using a PPARalpha antagonist. This occurs with a faster rate to that of direct
      inhibition of 3-hydroxy-3-methyglutaryl CoA reductase (HMG-CoA reductase) using
      lovastatin in living cells, demonstrating the potential therapeutic value of
      modulating host cell pathways as part of a strategy to eliminate chronic HCV
      infection.

PMID- 19747706
TI  - An evaluation of transmission routes for low pathogenicity avian influenza virus
      among chickens sold in live bird markets.
AB  - Many theories about the modes of avian influenza virus (AIV) transmission have
      been proposed, but few have been quantified, and none within a flock or live bird
      market (LBM) setting where birds are often kept in stacked cages. We describe a
      novel experimental design and the results collected for the purpose of estimating
      transmission rates specific to the potential modes of AIV transmission within an
      LBM. Chickens of the strains and ages found in California LBMs were inoculated
      with low pathogenicity AIV H6N2. Aerosol exposure was found to be the most
      important route of transmission for this H6N2 AIV. The handling of infectious
      chickens resulted in the transmission of H6N2 AIV, though the virus was not
      detectible by rRT-PCR. Chickens with fecal exposure to infected birds (median=8.0
      DPI) had detectable virus earlier than in those with aerosol exposure only
      (median=10.0 DPI). Changes in the hemagglutinin sequence were not found to be
      associated with oropharyngeal or cloacal shedding in this study.

PMID- 19747707
TI  - N-terminally truncated C protein, CNDelta25, of human parainfluenza virus type 3
      is a potent inhibitor of viral replication.
AB  - The C protein of human parainfluenza virus type 3 (HPIV3) is a multifunctional
      accessory protein that inhibits viral transcription and interferon (IFN)
      signaling. In the present study, we found that removal of N-terminal 25 or 50
      amino acid residues from the C protein (CNDelta25 or CNDelta50) totally abolished
      viral RNA synthesis in the HPIV3 minigenome system. Further N-terminal or C
      terminal deletion impaired the inhibitory ability of CNDelta25 and CNDelta50.
      Subsequent mutagenesis analysis suggested that the N-terminal-charged amino acid
      residues (K3, K6, K12, E16, and R24) contribute to the higher inhibition caused
      by CNDelta25 than the C protein. Consistent with viral RNA synthesis inhibition,
      the growth of HPIV3 was significantly decreased by 5 logs in HeLa-derived cell
      line expressing CNDelta25. Interestingly, replication of respiratory syncytial
      virus (RSV), another important respiratory tract pathogen, was also strongly
      inhibited in the presence of CNDelta25. These findings provide a promising
      potential to use CNDelta25 as an antiviral agent against the clinically important
      respiratory tract diseases caused by HPIV3 and RSV.

PMID- 19747708
TI  - Alterations in caspase cleavage motifs of NP and M2 proteins attenuate virulence
      of a highly pathogenic avian influenza virus.
AB  - The NP and M2 proteins of influenza A viruses are cleaved by caspases. M2
      cleavage occurs with both human and avian viruses, whereas NP cleavage is
      specific for human strains. In the present study we have modified fowl plaque
      virus (A/FPV/Rostock/34 (H7 N1)) by introducing the NP cleavage site and removing
      the M2 cleavage site and have analyzed the effects of these modifications on
      virus growth and pathogenicity. The viruses generated by reversed genetics were:
      mutant NPgd which had the NP cleavage site METD downward arrowG(17), recombinant
      wild type virus and mutant NPdel with the non-cleavable motifs METGG(17) and MET
      G(17), respectively, and mutant M2nn in which the M2 cleavage site VDVD downward
      arrowDG(89) of wild type virus was replaced by the non-cleavable sequence
      VNVNDG(89). Mutant NPgd replicated in cell cultures and in chicken embryos
      equally well as wild type virus and mutant NPdel. This observation was in
      contrast to previous results obtained with the human WSN strain that required
      caspase cleavage of NP for optimal virus growth. Thus, it appears that
      acquisition of the NP cleavage site is an adaptive mutation promoting
      interspecies transmission from an avian to a mammalian host. Like mutant NPgd,
      mutant M2nn virus did not show replication defects in cell culture and in chicken
      embryos. However, there was a reduction in pathogenicity for chickens, that was
      moderate with NPgd and dramatic with M2nn. Single injections with NPgd and M2nn
      at low doses induced high antibody titers and protected chickens from lethal FPV
      infection. These results show that a highly pathogenic avian influenza virus can
      be attenuated by modulating the caspase cleavage sites of NP and M2 and that
      these sites should be considered as novel targets for the design of live
      vaccines.

PMID- 19747709
TI  - Structural and biological constraints on diversity of regions immediately
      upstream of cleavage sites in calicivirus precursor proteins.
AB  - To address the regulation and evolution of precursor protein cleavability in
      caliciviruses, we examined constraints on diversity of upstream regions of
      calicivirus precursor cleavage sites. We performed alanine scanning and
      supplementary mutagenesis of amino acids at P1, P2, P3, and P4 sites using four
      viruses representing the four major genera of the family Caliciviridae. This
      study complements previous mutagenesis studies and shows strong restrictions in
      mutations at the P1 and P4 sites for effective cleavage reactions. By contrast,
      such restrictions were less frequently observed at the P2 and P3 sites. Shannon
      entropy analysis of the reported sequences showed that the P2, P3, and P4 sites
      allow variations in amino acid size within a calicivirus genus whereas the P1
      sites do not. Notably, the human sapovirus precursor protein exceptionally
      retains a basic rather than aromatic amino acid at the P4 site of the NS4/NS5
      cleavage site in reported strains, and a substitution from basic to aromatic
      amino acid significantly enhanced cleavability at this site. Taken together,
      these data suggest the existence of (i) structural constraints on the P1 site
      that restrict size changes within each calicivirus genus, (ii) plastic substrate
      surfaces that accommodate size variation at the P2, P3, and P4 sites and modulate
      their own cleavabilities, and (iii) biological constraints on the P4 site that
      maintain the lower cleavability of the NS4/NS5 site in sapovirus.

PMID- 19747710
TI  - Recovery of acids from anaerobic acidification broth by liquid-liquid extraction.
AB  - In this study, anaerobic acidification of sugar beet processing wastes and
      subsequent liquid-liquid extraction of produced fermentation metabolites were
      investigated. The aim of extraction experiments was to asses the influence of pH
      and extractant (trioctylphosphine oxide (TOPO) in kerosene) concentrations on the
      recovery of volatile fatty acids (VFAs) from fermentation broth. The effect of
      TOPO in kerosene concentration was as crucial as the effect of pH on the recovery
      of VFAs via extraction. Consequently, pH 2.5 was determined as optimum. At this
      pH, percent recoveries of VFAs were changed from 43% to 98%, depending on the
      type of the acid extracted (acetic, butyric, propionic and valeric acids) and the
      concentration of TOPO in kerosene (5-20%). As the concentration of TOPO in
      kerosene was increased, efficiency of extraction was increased. As a result,
      highest VFA recoveries (61-98%) were observed at 20% TOPO in kerosene with
      distribution ratio values ranging between 1.54 and 40.79. At pH 2.5, the increase
      in TOPO concentration directly increased the chemical oxygen demand (COD) removal
      efficiencies, as it does for total VFA recovery. Up to 72% COD removals were
      achieved, at 20% TOPO in kerosene at pH 2.5, while the removal efficiencies
      remained between 19% and 22% at pH 5.5.

PMID- 19747711
TI  - Effect of Moringa oleifera lectin on development and mortality of Aedes aegypti
      larvae.
AB  - Aedes aegypti larvae have developed tolerance to many insecticides used for
      mosquito control. Moringa oleifera seeds contain a water-soluble lectin (WSMoL)
      and this paper reports the effect of M. oleifera seed extracts (MoE(1-15)) and
      WSMoL on development and survival of A. aegypti larvae. WSMoL peptide from in-gel
      trypsin digestion is also described. MoE(1-15) showed hemagglutinating activity
      and WSMoL had similarity with flocculating proteins from M. oleifera seeds.
      MoE(1) and MoE(3) delayed larval development which stopped in the third instar
      (L3) in MoE(6) and MoE(15). Significant (p<0.0001) larval mortality was only
      detected in MoE(15). Native WSMoL showed larvicidal activity (LC(50) 0.197 mg mL(
      1)) and heated lectin, without hemagglutinating activity, did not kill fourth
      instar (L4) larvae. Optical microscopy showed that live L4 from MoE(1) presented
      underlying epithelium, increased gut lumen and hypertrophic segments; dead L4
      from WSMoL were absent of underlying epithelium, had increased gut lumen and
      hypertrophic segments. The presence of hemagglutinating activity in the extracts
      suggests that soluble lectin promotes the delay of larval development and
      mortality; furthermore, the absence of larvicidal activity in heat-denatured
      WSMoL strengthens the involvement of lectin in this activity mechanism.

PMID- 19747712
TI  - Overexpression of heat shock protein 27 in squamous cell carcinoma of the uterine
      cervix.

PMID- 19747713
TI  - Mercury distribution and exchanges between the Amazon River and connected
      floodplain lakes.
AB  - This work presents the distribution and the partition of mercury (Hg) in the
      Curuai floodplain lakes along the Amazon River. The maximum Total Filtered Hg (T
      FHg) concentrations in the floodplain lakes (28 to 52 pmol L(-1)) coincide with
      the maximum T-FHg concentrations of the Amazon River and are measured during the
      flooding period. The lowest T-FHg values (3 to 5 pmol L(-1)) are observed during
      the flood peak of the mainstream, during the rainy season, when waters are
      diluted by the local rainfall. In this system, Hg is mainly transported in the
      particulate phase, confirmed by elevated values of the Hg partition coefficient
      (4.77<K(d) (Hg)<5.83 Lkg(-1)). The highest Total Particulate Hg (T-PHg)
      concentrations (47-478 pmol L(-1)) in the lakes are measured during the dry
      season when they are isolated from the mainstream. This enrichment is due to the
      elevated TSS content associated to the re-suspension of the bottom sediments by
      the wind action and the bioturbation in shallow water lakes. In the flooded
      system, the lakes show different geochemical characteristics that control the Hg
      distribution and partition. In the white water (WW) lakes, characterized by
      oxidative neutral waters and highest TSS contents (till 2041 mg L(-1)), the T-PHg
      is associated to the particulate organic matter mainly during the dry season,
      while the T-FHg and T-FMn concentrations are correlated. In the black water (BW)
      lakes that show reductive pH conditions and lowest TSS load (2 to 5 2 mg L(-1)),
      P-iron and T-PHg display a positive relationship whereas the redox conditions
      favor the desorption of Hg from the particulate to the filtered phase. The
      mercury mass budget estimated in this study confirms that the Curuai floodplain
      system acts as a particulate mercury trap, with a net storage of particulate Hg
      of 150 kg PHg year(-1).

PMID- 19747714
TI  - Changing blood lead levels and DNA damage (comet assay) among immigrant women in
      Taiwan.
AB  - BACKGROUND: International marriage has had a rapid growth in recent years in
      Taiwan. However, little is known about the blood lead levels and DNA damage
      levels among immigrant women from resource-limited countries. OBJECTIVE: This
      study (a) explored differences between immigrant women and native women in
      demographic characteristics, blood lead levels, and DNA damage levels, and (b)
      identified risk factors that are associated with blood lead concentrations and
      DNA damage levels after immigration. METHODS: We used a structured questionnaire
      to collect data on socio-demographic status from (a) 71 immigrant women who had
      resettled in 2006 in Taichung, Taiwan and (b) 83 native women who live in the
      same area. Each study participant provided blood samples for lead and metal
      measurements, complete blood count examination, and the comet assay to measure
      degree of DNA damage. RESULTS: Immigrant women had higher mean blood lead
      concentration (2.23+/-1.63 vs. 1.63+/-1.00 microg/dl; p=0.04) and lower mean
      blood zinc level (6.22+/-2.22 vs. 6.89+/-2.44 mg/l; p=0.07) than native women.
      Resettlement time was a determinant to decrease blood lead and DNA damage levels
      among immigrants in Taiwan. Multiple linear regression analysis confirmed a
      statistically significant association between blood lead level and DNA damage,
      while zinc had a protective effect. CONCLUSIONS: Public health agencies should
      focus on primary prevention and providing screening programs for this vulnerable
      population. An immigrant women's cohort should been established to follow-up and
      improve for elevated lead exposure families.

PMID- 19747715
TI  - Decision support system for the evaluation of urban air pollution control
      options: application for particulate pollution in Thessaloniki, Greece.
AB  - Development of strategies to control urban air pollution is a complex and multi
      disciplinary process involving a wide range of scientists with different
      expertise and interests. This paper presents an integrated assessment
      methodological scheme for the evaluation of air pollution control measures that
      are put forward in order to reduce sufficiently air pollution levels in urban
      areas. Forming long-term, efficient air pollution control strategies requires
      knowledge of the costs associated with their implementation, the emission
      inventories and emission reductions to be achieved, as well as the concentration
      variations that represent air quality levels in the area examined. In contrast to
      the majority of the currently employed assessment approaches, the presented
      scheme enables the evaluation of any proposed air pollution control option in
      terms of its combined impact on air quality and social welfare, by correlating
      economic and health impact assessment issues. The approach presented in this
      paper brings together air quality modelling and mathematical programming
      techniques and provides a decision support system for the determination of
      optimal bundles of air pollution control options according to the particular
      features and needs of the areas examined. Both cost-effectiveness and cost
      benefit approaches are taken into account in order to put the problem on the
      basis of economic efficiency from a societal perspective. The methodology is
      implemented for the case of Thessaloniki, Greece, which is selected on the
      grounds that the area is considered as one of the most polluted--if not the most
      polluted--cities within Europe, especially with respect to airborne particles.

PMID- 19747716
TI  - CA125 (MUC16) tumor antigen selectively modulates the sensitivity of ovarian
      cancer cells to genotoxic drug-induced apoptosis.
AB  - OBJECTIVE: Little is known about the biological functions of CA125/MUC16 tumor
      antigen. Here, we examined the role of CA125/MUC16 in regulating the sensitivity
      of epithelial ovarian carcinoma (EOC) cells to different drugs. METHODS: An
      endoplasmic reticulum targeted single-chain antibody (scFv) was used to down
      regulate cell surface expression of CA125/MUC16 in NIH:OVCAR3 cells and the C
      terminal domain (CTD) of MUC16 was ectopically expressed in CA125-negative SKOV3
      cells. Sensitivity to genotoxic agents and to inhibitors of microtubule
      depolymerization was examined in NIH:OVCAR3 and SKOV3 cell sublines. Cell
      viability was determined by XTT assay, apoptosis by propidium iodide staining and
      caspase activation by Western blot and fluorogenic assay. RESULTS: Down
      regulation of cell surface MUC16 decreases cisplatin IC(50) by 5-fold in
      NIH:OVCAR3 cells but does not affect paclitaxel IC(50). We found that the
      sensitivity to other genotoxic agents such as cyclophosphamide, doxorubicine and
      etoposide was also increased by down-regulation of MUC16. Caspase-9 and caspase-3
      activation also significantly augmented in cisplatin-treated NIH:OVCAR3 cells
      expressing the anti-MUC16 scFv. Ectopic expression of MUC16 CTD has the opposite
      effect. Cisplatin sensitivity and caspases activation are decreased by the
      ectopic expression of MUC16 CTD in SKOV3 cells. CONCLUSIONS: CA125/MUC16
      selectively modulates the sensitivity of EOC cells to genotoxic agents. The MUC16
      CTD appears to be sufficient to promote cisplatin resistance.

PMID- 19747717
TI  - The exosome regulates circadian gene expression in a posttranscriptional negative
      feedback loop.
AB  - The eukaryotic circadian oscillators consist of autoregulatory negative feedback
      loops. However, little is known about the role of posttranscriptional regulation
      of RNA in circadian oscillators. In the Neurospora circadian negative feedback
      loop, FRQ and FRH form the FFC complex that represses frq transcription. Here, we
      show that FFC also binds frq RNA and interacts with the exosome to regulate frq
      RNA decay. Consequently, frq RNA is robustly rhythmic as it is more stable when
      FRQ levels are low. Silencing of RRP44, the catalytic subunit of the exosome,
      elevates frq RNA levels and impairs clock function. In addition, rrp44 is a clock
      controlled gene and a direct target of the WHITE COLLAR complex, and RRP44
      controls the circadian expression of some ccgs. Taken together, these results
      suggest that FFC and the exosome are part of a posttranscriptional negative
      feedback loop that regulates frq transcript levels and the circadian output
      pathway.

PMID- 19747718
TI  - Effects of dilution and centrifugation on the survival of spermatozoa and the
      structure of motile sperm cell subpopulations in refrigerated Catalonian donkey
      semen.
AB  - The aim of this work was to study the effects of dilution and centrifugation
      (i.e., two methods of reducing the influence of the seminal plasma) on the
      survival of spermatozoa and the structure of motile sperm cell subpopulations in
      refrigerated Catalonian donkey (Equus asinus) semen. Fifty ejaculates from nine
      Catalonian jackasses were collected. Gel-free semen was diluted 1:1, 1:5 or 1:10
      with Kenney extender. Another sample of semen was diluted 1:5, centrifuged, and
      then resuspended with Kenney extender until a final dilution of 25x10(6) sperm/ml
      was achieved (C). After 24 h, 48 h or 72 h of refrigerated storage at 5 degrees
      C, aliquots of these semen samples were incubated at 37 degrees C for 5 min. The
      percentage of viable sperm was determined by staining with eosin-nigrosin. The
      motility characteristics of the spermatozoa were examined using the CASA system
      (Microptic, Barcelona, Spain). At 24h, more surviving spermatozoa were seen in
      the more diluted and in the centrifuged semen samples (1:1 48.71%; 1:5 56.58%,
      1:10 62.65%; C 72.40%). These differences were maintained at 48 h (1:1 34.31%,
      1:5 40.56%, 1:10 48.52%, C 66.30%). After 72 h, only the C samples showed a
      survival rate of above 25%. The four known donkey motile sperm subpopulations
      were maintained by refrigeration. However, the percentage of motile sperms in
      each subpopulation changed with dilution. Only the centrifuged samples, and only
      at 24h, showed exactly the same motile sperm subpopulation proportions as
      recorded for fresh sperm. However, the 1:10 dilutions at 24 and 48 h, and the
      centrifuged semen at 48 h, showed few variations compared to fresh sperm. These
      results show that the elimination of seminal plasma increases the survival of
      spermatozoa and the maintenance of motility patterns. The initial sperm
      concentration had a significant (P<0.05) influence on centrifugation efficacy,
      but did not influence the number of spermatozoa damaged by centrifugation. In
      contrast, the percentage of live spermatozoa in the fresh semen significantly
      influenced the number of spermatozoa damaged by centrifugation, but not
      centrifugation efficacy.

PMID- 19747719
TI  - Influence of curing protocol on selected properties of light-curing polymers:
      degree of conversion, volume contraction, elastic modulus, and glass transition
      temperature.
AB  - OBJECTIVES: The purpose of this study was to investigate the effect of light
      curing protocol on degree of conversion (DC), volume contraction (C), elastic
      modulus (E), and glass transition temperature (T(g)) as measured on a model
      polymer. It was a further aim to correlate the measured values with each other.
      METHODS: Different light-curing protocols were used in order to investigate the
      influence of energy density (ED), power density (PD), and mode of cure on the
      properties. The modes of cure were continuous, pulse-delay, and stepped
      irradiation. DC was measured by Raman micro-spectroscopy. C was determined by
      pycnometry and a density column. E was measured by a dynamic mechanical analyzer
      (DMA), and T(g) was measured by differential scanning calorimetry (DSC). Data
      were submitted to two- and three-way ANOVA, and linear regression analyses.
      RESULTS: ED, PD, and mode of cure influenced DC, C, E, and T(g) of the polymer. A
      significant positive correlation was found between ED and DC (r=0.58), ED and E
      (r=0.51), and ED and T(g) (r=0.44). Taken together, ED and PD were significantly
      related to DC and E. The regression coefficient was positive for ED and negative
      for PD. Significant positive correlations were detected between DC and C
      (r=0.54), DC and E (r=0.61), and DC and T(g) (r=0.53). Comparisons between
      continuous and pulse-delay modes of cure showed significant influence of mode of
      cure: pulse-delay curing resulted in decreased DC, decreased C, and decreased
      T(g). Influence of mode of cure, when comparing continuous and step modes of
      cure, was more ambiguous. SIGNIFICANCE: A complex relationship exists between
      curing protocol, microstructure of the resin and the investigated properties. The
      overall performance of a composite is thus indirectly affected by the curing
      protocol adopted, and the desired reduction of C may be in fact a consequence of
      the decrease in DC.

PMID- 19747720
TI  - Sickle-cell disease: an ounce of prevention, a pound of cure.

PMID- 19747721
TI  - Bacteraemia in Kenyan children with sickle-cell anaemia: a retrospective cohort
      and case-control study.
AB  - BACKGROUND: In sub-Saharan Africa, more than 90% of children with sickle-cell
      anaemia die before the diagnosis can be made. The causes of death are poorly
      documented, but bacterial sepsis is probably important. We examined the risk of
      invasive bacterial diseases in children with sickle-cell anaemia. METHODS: This
      study was undertaken in a rural area on the coast of Kenya, with a case-control
      approach. We undertook blood cultures on all children younger than 14 years who
      were admitted from within a defined study area to Kilifi District Hospital
      between Aug 1, 1998, and March 31, 2008; those with bacteraemia were defined as
      cases. We used two sets of controls: children recruited by random sampling in the
      same area into several studies undertaken between Sept 1, 1998, and Nov 30, 2005;
      and those born consecutively within the area between May 1, 2006, and April 30,
      2008. Cases and controls were tested for sickle-cell anaemia retrospectively.
      FINDINGS: We detected 2157 episodes of bacteraemia in 38 441 admissions (6%).
      1749 of these children with bacteraemia (81%) were typed for sickle-cell anaemia,
      of whom 108 (6%) were positive as were 89 of 13 492 controls (1%). The organisms
      most commonly isolated from children with sickle-cell anaemia were Streptococcus
      pneumoniae (44/108 isolates; 41%), non-typhi Salmonella species (19/108; 18%),
      Haemophilus influenzae type b (13/108; 12%), Acinetobacter species (seven of 108;
      7%), and Escherichia coli (seven of 108; 7%). The age-adjusted odds ratio for
      bacteraemia in children with sickle-cell anaemia was 26.3 (95% CI 14.5-47.6),
      with the strongest associations for S pneumoniae (33.0, 17.4-62.8), non-typhi
      Salmonella species (35.5, 16.4-76.8), and H influenzae type b (28.1, 12.0-65.9).
      INTERPRETATION: The organisms causing bacteraemia in African children with sickle
      cell anaemia are the same as those in developed countries. Introduction of
      conjugate vaccines against S pneumoniae and H influenzae into the childhood
      immunisation schedules of African countries could substantially affect survival
      of children with sickle-cell anaemia. FUNDING: Wellcome Trust, UK.

PMID- 19747722
TI  - Cleft lip and palate.
AB  - Clefts of the lip and palate are generally divided into two groups, isolated
      cleft palate and cleft lip with or without cleft palate, representing a
      heterogeneous group of disorders affecting the lips and oral cavity. These
      defects arise in about 1.7 per 1000 liveborn babies, with ethnic and geographic
      variation. Effects on speech, hearing, appearance, and psychology can lead to
      longlasting adverse outcomes for health and social integration. Typically,
      children with these disorders need multidisciplinary care from birth to adulthood
      and have higher morbidity and mortality throughout life than do unaffected
      individuals. This Seminar describes embryological developmental processes,
      epidemiology, known environmental and genetic risk factors, and their
      interaction. Although access to care has increased in recent years, especially in
      developing countries, quality of care still varies substantially. Prevention is
      the ultimate objective for clefts of the lip and palate, and a prerequisite of
      this aim is to elucidate causes of the disorders. Technological advances and
      international collaborations have yielded some successes.

PMID- 19747723
TI  - Mitral stenosis.
AB  - Mitral stenosis is a common disease that causes substantial morbidity worldwide.
      The disease is most prevalent in developing countries, but is increasingly being
      identified in an atypical form in developed countries. All treatments that
      increase valve area improve morbidity. Mortality improves with surgery; the
      benefit of percutaneous balloon valvuloplasty to mortality might be similar to
      that of surgery but needs further study. Percutaneous balloon valvuloplasty is
      the treatment of choice for patients in whom treatment is indicated, except for
      those with suboptimum valve morphology, and even these patients are sometimes
      treated with this procedure if surgery is not feasible or if surgical risk is
      prohibitive. We review the pathology, diagnosis, and treatment options for
      patients with mitral stenosis.

PMID- 19747724
TI  - Trace element accumulation in Cassiopea sp. (Scyphozoa) from urban marine
      environments in Australia.
AB  - Jellyfishes are robust, short-lived animals, tolerant to a wide range of
      environmental conditions and pollutants. The benthic jellyfish, Cassiopea sp. was
      collected from five locations along the north and eastern coast of Australia and
      analysed for trace elements to determine if this species has potential as a
      marine biomonitor. Both the oral arm and bell tissues readily accumulated
      aluminium, arsenic, barium, cadmium, chromium, copper, iron, manganese and zinc
      above ambient seawater levels. In contrast, lithium appeared to be actively
      regulated within the tissues while calcium, magnesium and strontium reflected the
      ambient environment. The multi-element signatures showed spatial variation,
      reflecting the geographical separations between locations, with locations closer
      together showing more similar elemental patterns. The combination of
      bioaccumulative capacity, life history traits and biophysical aspects indicate
      that this species has high potential as a biomonitor in coastal marine systems.

PMID- 19747725
TI  - Characterization of valvular interstitial cell function in three dimensional
      matrix metalloproteinase degradable PEG hydrogels.
AB  - Valvular interstitial cells (VICs) maintain functional heart valve structure and
      display transient fibroblast and myofibroblast properties. Most cell
      characterization studies have been performed on plastic dishes; while insightful,
      these systems are limited. Thus, a matrix metalloproteinase (MMP) degradable
      poly(ethylene glycol) (PEG) hydrogel system is proposed in this communication as
      a useful tool for characterizing VIC function in 3D. When encapsulated, VICs
      attained spread morphology, and proliferated and migrated as shown through real
      time cell microscopy. Additionally, fibronectin derived pendant RGD was
      incorporated into the system to promote integrin binding. As RGD concentration
      increased from 0 to 2000 microM, VIC process extension and integrin
      alpha(v)beta(3) binding increased within two days. By day 10, integrin binding
      was equalized between conditions. VIC morphology and rate of process extension
      were also increased through decreasing the hydrogel matrix density presented to
      the cells. VIC differentiation in response to exogenously delivered transforming
      growth factor-beta1 (TGF-beta1) was also examined within the hydrogel networks.
      TGF-beta1 increased expression of alpha smooth muscle actin (alphaSMA) and
      collagen-1 at both the mRNA and protein level by day 2 of culture, indicating
      myofibroblast differentiation, and was sustained over the course of the study (2
      weeks). These studies demonstrate the utility, flexibility, and biological
      activity of this MMP-degradable system for the characterization of VICs, an
      important cell population for tissue engineering viable valve replacements and
      understanding valvular pathobiology.

PMID- 19747726
TI  - Endoplasmic reticulum Ca(2+) release through ryanodine and IP(3) receptors
      contributes to neuronal excitotoxicity.
AB  - Overactivation of ionotropic glutamate receptors induces a Ca(2+) overload into
      the cytoplasm that leads neurons to excitotoxic death, a process that has been
      linked to several neurodegenerative disorders. While the role of mitochondria and
      its involvement in excitotoxicity have been widely studied, the contribution of
      endoplasmic reticulum (ER), another crucial intracellular store in maintaining
      Ca(2+) homeostasis, is not fully understood. In this study, we analyzed the
      contribution of ER-Ca(2+) release through ryanodine (RyR) and IP(3) (IP(3)R)
      receptors to a neuronal in vitro model of excitotoxicity. NMDA induced a dose
      dependent neuronal death, which was significantly decreased by ER-Ca(2+) release
      inhibitors in cortical neurons as well as in organotypic slices. Furthermore,
      ryanodine and 2APB, RyR and IP(3)R inhibitors respectively, attenuated NMDA
      triggered intracellular Ca(2+) increase and oxidative stress, whereas 2APB
      reduced mitochondrial membrane depolarization and caspase-3 cleavage. Consistent
      with ER-Ca(2+) homeostasis disruption, we observed that NMDA-induced ER stress,
      characterized here by eIF2alpha phosphorylation and over-expression of GRP
      chaperones which were regulated by ER-Ca(2+) release inhibitors. These results
      demonstrate that Ca(2+) release from ER contributes to neuronal death by both
      promoting mitochondrial dysfunction and inducing specific stress and apoptosis
      pathways during excitotoxicity.

PMID- 19747727
TI  - Stimulatory effect of growth hormone-releasing hormone (GHRH(1-29)NH2) on the
      proliferation, VEGF and chromogranin A secretion by human neuroendocrine tumor
      cell line NCI-H727 in vitro.
AB  - Growth hormone-releasing hormone (GHRH) and its receptors have been implicated in
      a variety of cellular processes like cell survival, proliferation, apoptosis,
      angiogenesis and neoplastic transformation of various non-pituitary tissues.
      Here, we investigated for the first time the in vitro effect of GHRH(1-29)NH2 on
      the proliferation and the secretion of vascular endothelial growth factor (VEGF)
      and chromogranin A by the human bronchial neuroendocrine tumor cells NCI-H727.
      GHRH(1-29)NH2 at the concentrations of 10(-8)-10(-6)M increased the proliferation
      of these cells and this effect was associated with a statistically significant
      increase in VEGF and chromogranin A secretion into the supernatants of the tested
      cells. Our findings indicate that GHRH functions as a trophic hormone for
      bronchial neuroendocrine (NET) tumors.

PMID- 19747728
TI  - Smoking and alcohol intake as risk factors for myelodysplastic syndromes (MDS).
AB  - The term myelodysplastic syndromes (MDS) include a diverse group of diseases in
      which the bone marrow production of blood cells is disrupted. In spite of the
      wealth of information on therapeutic options, little is known about the
      epidemiology of MDS, including population variations and risk factors. A
      narrative review of published literature and meta-analyses were conducted,
      identifying and summarizing key reports that describe the association between
      smoking, alcohol and MDS. There were 10 case-control studies that looked at the
      association between smoking and MDS, for a total of 1839 cases and 2831 controls.
      The meta-estimate for the association between ever smoking and MDS was 1.45 (95%
      CI: 1.21-1.74), with heterogeneity among studies (p=0.05), but no evidence of
      publication bias. The relationship between alcohol consumption and MDS has been
      examined in five studies, including 745 cases and 1642 controls. The overall
      association was 1.31 (95% CI: 0.79-2.18), with significant heterogeneity
      (p=0.003) and no evidence of publication bias. This re-analysis of published data
      strongly suggests that smoking is significantly associated with MDS, while
      alcohol does not seem to play a major role in MDS etiology. Large epidemiological
      studies incorporating biomarkers of exposure, along with pooled analysis are
      needed to better address the contribution of lifestyle factors to the development
      of MDS.

PMID- 19747729
TI  - Arsenic-induced pericardial and pleural effusion without acute promyelocytic
      leukemia differentiation syndrome.

PMID- 19747731
TI  - Multicentric Castleman disease complicated by tumor lysis syndrome after systemic
      chemotherapy.

PMID- 19747730
TI  - Anti-leukemia activity of a bacterial toxin with natural specificity for LFA-1 on
      white blood cells.
AB  - The oral bacterium, Aggregatibacter actinomycetemcomitans, produces a leukotoxin
      (LtxA) that is specific for white blood cells (WBCs) from humans and Old World
      primates by interacting with lymphocyte function antigen-1 (LFA-1) on susceptible
      cells. To determine if LtxA could be used as a therapeutic agent for the
      treatment of WBC diseases, we tested the in vitro and in vivo anti-leukemia
      activity of the toxin. LtxA kills human malignant WBC lines and primary leukemia
      cells from acute myeloid leukemia patients, but healthy peripheral blood
      mononuclear cells (PBMCs) are relatively resistant to LtxA-mediated cytotoxicity.
      Levels of LFA-1 on cell lines correlated with killing by LtxA and the toxin
      preferentially killed cells expressing the activated form of LFA-1. In a SCID
      mouse model for human leukemia, LtxA had potent therapeutic value resulting in
      long-term survival in LtxA-treated mice. Intravenous infusion of LtxA into a
      rhesus macaque resulted in a drop in WBC counts at early times post-infusion;
      however, red blood cells, platelets, hemoglobin and blood chemistry values
      remained unaffected. Thus, LtxA may be an effective and safe novel therapeutic
      agent for the treatment of hematologic malignancies.

PMID- 19747732
TI  - Diabetes insipidus as main presentation of non-Hodgkin's lymphoma with
      hypophyseal involvement: two case reports.

PMID- 19747733
TI  - Apoptosis-associated acetylation on histone H2B is an epitope for lupus
      autoantibodies.
AB  - OBJECTIVE: Nucleosomes have been identified as a key autoantigen in systemic
      lupus erythematosus (SLE). Nucleosomes are present in the circulation due to a
      disturbed apoptosis and/or an insufficient clearance in SLE. During apoptosis,
      histones can be modified, thereby making them more immunogenic. Recently, we
      showed the importance of apoptosis-induced acetylation of histone H4 in the
      pathogenesis of SLE. The lupus-derived antibody LG11-2 was previously shown to
      react with the N-terminal tail of histone H2B, which contains amino acid residues
      that can be modified including phosphorylation of serine 14, known to occur
      during apoptosis. Here, we evaluate whether apoptosis-induced histone
      modifications on H2B exist that are targeted by LG11-2 or lupus-derived plasmas.
      METHODS: Immunofluorescence staining and western immunoblot analysis of control,
      apoptotic and trichostatin A-treated cells/chromatin were performed with
      monoclonal antibody LG11-2. Reactivity of LG11-2 and plasmas from lupus mice and
      SLE patients with acetylated and/or phosphorylated H2B peptides was determined in
      competition ELISA. RESULTS: LG11-2 showed enhanced reactivity with apoptotic and
      hyperacetylated H2B compared to normal H2B. This enhanced reactivity was due to
      the acetylation of lysine 12 in H2B. This modification was also recognized by
      autoantibodies from pre-diseased lupus mice, but to a lesser extent by plasmas of
      diseased lupus mice and lupus patients. CONCLUSIONS: The apoptosis-induced
      acetylation on H2BK12 is a target for autoantibodies in SLE. Since the anti
      H2BK12ac reactivity was mainly found in pre-diseased lupus mice, this epitope
      seems important in the early phase of the anti-chromatin autoimmune response with
      subsequent epitope spreading to unmodified H2B.

PMID- 19747734
TI  - Humanized cobra venom factor decreases myocardial ischemia-reperfusion injury.
AB  - Cobra venom factor (CVF) is a complement activating protein in cobra venom, which
      functionally resembles C3b, and has been used for decades for decomplementation
      of serum to investigate the role of complement in many model systems of disease.
      The use of CVF for clinical practice is considered impractical because of
      immunogenicity issues. Humanization of CVF was recently demonstrated to yield a
      potent CVF-like molecule. In the present study, we demonstrate that mice treated
      with recombinant humanized CVF (HC3-1496) are protected from myocardial ischemia
      reperfusion (MI/R) injuries with resultant preservation of cardiac function.
      Also, C3 deposition in the myocardium following MI/R was not observed following
      treatment with HC3-1496. HC3-1496 led to complement activation and depletion of
      C3, but preserved C5 titers. These data suggest, unlike CVF, HC3-1496 does not
      form a C5 convertase in the mouse, similar to recent studies in human
      sera/plasma. These results suggest that humanized CVF (HC3-1496) protects the
      ischemic myocardium from reperfusion injuries induced by complement activation
      and represents a novel anti-complement therapy for potential clinical use.

PMID- 19747735
TI  - The location of aluminium in protoplasts and suspension cells taken from Coffea
      arabica L. with different tolerance of Al.
AB  - Biotechnological advances in coffee research (in vitro manipulation,
      multiplication, generation and development of transgenic coffee plants with
      specific traits like high yield and good quality) have contributed to description
      of the metabolic pathways involved in the response mechanisms to environmental
      factors like abiotic stress. Coffea arabica L. plants grow in acidic soils, and
      therefore aluminium (Al) toxicity is a major negative impact on crop
      productivity. To understand Al toxicity mechanisms in cells via the Al absorption
      kinetic, we isolated protoplasts from two C. arabica L. suspension cell lines: Al
      sensitive (L2) and Al-tolerant (LAMt). Protoplasts of LAMt line exhibited lower
      Al absorption levels than protoplasts of the L2 line. Use of two fluorescent
      tracers (morin and calcofluor white) indicated that Al interacts with internal
      cell structures, such as the plasma membrane and nucleus, with differences in
      both cell lines. Al-tolerance in the LAMt is probably associated with the cell
      wall as well as intracellular structures. These data will help to better
      understand Al toxicity in C. arabica, and Al toxicity mechanisms in plant cells.

PMID- 19747736
TI  - Hypokalemia is associated with lengthening of QT interval in psychiatric patients
      on admission.
AB  - Several studies have revealed a relatively high frequency of hypokalemia in the
      general psychiatric population. This may be explained by adrenergic stimulation
      observed in the acute phase of psychiatric disorders. Little is known about the
      effects of hypokalemia on cardiac repolarisation in these circumstances. The
      current study was designed to determine if the hypokalemia observed among
      patients with acute psychiatric disorders can cause significant QT interval
      prolongation, and thus increase the risk of ventricular arrhythmia.
      Electrocardiograms were obtained in 282 non-selected patients admitted to a
      psychiatric unit. Heart-rate adjusted QT intervals (QTc) were compared to serum
      potassium levels and to other risk factors for QT prolongation (bradycardia, age,
      gender, and administration of antipsychotics). Hypokalemia, diagnosed in more
      than 11% of the patients, was associated with a significantly longer QTc interval
      (means 423.5+/-40 ms vs 408.5+/-31 ms), as was female sex. Multiple linear
      regression analysis on the studied risk factors revealed that only hypokalemia
      and female sex were independently associated with lengthening of the QT interval.
      According to our results, hypokalemia seems to be one of the most important risk
      factors for QT prolongation. We therefore strongly recommend that psychiatric
      patients should be screened for hypokalemia on admission.

PMID- 19747737
TI  - Plasma levels of lipoprotein (a) in patients with major depressive disorders.
AB  - Depression and cardiovascular disease are among the most prevalent health
      problems. The evidence that depression is a risk factor for the development and
      progression of coronary heart disease has strengthened over the past several
      years, but the exact reasons are not yet clear. Elevated lipoprotein (a) (Lp(a))
      concentrations seem to be the major factor for the progression of the
      atherosclerosis and coronary heart disease. In this study, we measured the plasma
      levels of Lp(a) in 35 patients with major depressive disorder and 35 healthy
      controls. The two groups were matched by age and gender. Lp(a) measurement was
      performed using an immunoturbidimetric method. Total cholesterol was
      significantly lower in the patient group (mean +/-SD: 144.65+/-22.13 vs. 186.14+/
      34.48 mg/dl. The Lp(a) levels of the patient group differed significantly from
      control values. Patients with major depressive disorder had higher plasma levels
      of Lp(a) than healthy controls (34.94+/-18.01 vs. 20.08+/-11.27 mg/dl). The
      results of the present study suggest that the increase of Lp(a) may contribute to
      higher cardiovascular risk in patients with major depressive disorder.

PMID- 19747738
TI  - Parental satisfaction with post-adenotonsillectomy in the developing world.
AB  - AIM/BACKGROUND: Tonsillectomy with or without adenoidectomy is one of the most
      commonly performed surgical procedures by the otolaryngologists in the pediatric
      population. The aim of this study is to evaluate parental expectation and
      satisfaction following tonsillectomy with or without adenoidectomy. MATERIALS AND
      METHODS: Hospital-based prospective study of all consented parents whose children
      had tonsillectomy with or without adenoidectomy over a period of 13 months
      (February 2008 to February 2009) using a cross-sectional method. Pre- and post
      surgical questionnaire-based Interview was conducted for them and information
      retrieved included biodata, pre- and post-surgical symptoms on follow-up in the
      clinic of obstructive sleep apnoea, snoring, mouth breathing and rhinorrhea,
      parental expectation and satisfaction after surgery. All data were entered into
      statistical data using SPSS version 11 and analyzed and the results are presented
      in tables and figures. RESULTS: A total of 29 patients had adenotonsillar
      surgery, who were within the age range of 1.50-14 years with a mean age of 5.50
      (SD=4.06+/-0.75). M:F ratio was found to be 3:1 (22 males and 7 females). Parents
      were satisfied with the expected outcome in terms of symptoms post-operatively in
      96.6% while only one 3.4% were not satisfied. CONCLUSION: Majority of the parents
      (96.6%) were satisfied with the expectation of immediate resolution of symptoms;
      however, obstructive adenotonsillar hypertrophy remains an important problem to
      be solved to achieve total parental satisfaction in adenotonsillar operations.

PMID- 19747739
TI  - Disruption of zebrafish (Danio rerio) embryonic development after full life-cycle
      parental exposure to low levels of ethinylestradiol.
AB  - Exposure of fish to the synthetic estrogen ethinylestradiol (EE2) has been shown
      to induce a large set of deleterious effects. In addition to the negative impact
      of EE2 in reproductive endpoints, concern has recently increased on the potential
      effects of EE2 in fish embryonic development. Therefore, the present study aimed
      at examining the effects of EE2 on the full embryonic development of zebrafish in
      order to identify the actual phases where EE2 disrupts this process. Hence,
      zebrafish were exposed to environmentally relevant low levels of EE2, 0.5, 1 and
      2ng/L (actual concentrations of 0.19, 0.24 and 1ng/L, respectively) from egg up
      to eight months of age (F(1)), and the survival as well as the occurrence of
      abnormalities in their offsprings (F(2)), per stage of embryonic development, was
      investigated. A thorough evaluation of reproductive endpoints and transcription
      of vtg1 gene in the parental generation (F(1)) at adulthood, was performed. No
      significant differences could be observed for the two lowest EE2 treatments, in
      comparison with controls, whereas vtg1 transcripts were significantly elevated
      (40-fold) in the 2ng/L EE2 treatment. In contrast to the findings in the F(1)
      generation,a significant concentration-dependent increase in egg mortality
      between 8 and 24hours post-fertilization (hpf) was observed for all EE2
      treatments, when compared with controls. The screening of egg and embryo
      development showed a significant increase in the percentage of abnormalities at 8
      hpf for the highest EE2 concentration, a fact that might explain the increased
      embryo mortality at the 24 hpf time-point observation. Taken together, these
      findings indicate that the two lowest tested EE2 concentations impact late
      gastrulation and/or early organogenesis, whereas exposure to 2ng/L EE2 also
      disrupts development in the blastula phase. After early organogenesis has been
      completed (24 hpf), no further mortality was observed. These results show that
      increased embryo mortality occurs at EE2 levels below those inducing reproductive
      impairment and vtg1 gene induction in the male parental generation, thus
      suggesting that EE2 may impact some fish populations at levels below those
      inducing an increase in vtg1 transcripts. Hence, these findings have important
      implications for environmental risk assessment, strongly supporting the inclusion
      of embryonic development studies in the screening of endocrine disruption in wild
      fish populations.

PMID- 19747740
TI  - Land use, genetic diversity and toxicant tolerance in natural populations of
      Daphnia magna.
AB  - Provided that gene flow is not too high, selection by local environmental
      conditions in heterogeneous landscapes can lead to genetic adaptation of natural
      populations to their local habitat. Pollution with anthropogenic toxicants may
      create pronounced environmental gradients that impose strong local selection
      pressures. Toxic contaminants may also directly impact genetic structure in
      natural populations by exhibiting genotoxicity or by causing population declines
      resulting in genetic bottlenecks. Using populations of Daphnia magna established
      from the dormant egg banks of ponds located in a landscape dominated by
      anthropogenic impact, we aimed at detecting evidence for local adaptation to
      environmental contamination. We explored the relationship between land use around
      the 10 investigated ponds, population genetic diversity as measured by neutral
      genetic markers (polymorphic allozymes) and the tolerance of the populations
      originating from these ponds to acute lethal effects of two model toxicants, the
      pesticide carbaryl and the metal potassium dichromate. Genetic diversity of the
      populations as observed by neutral markers tended to be negatively impacted by
      agricultural land use intensity (Spearman rank correlation, R=-0.614, P=0.059),
      indicating that genetic bottlenecks may have resulted from anthropogenic impact.
      We experimentally observed differences in susceptibility to both carbaryl and
      potassium dichromate among the studied pond populations of D. magna (analysis of
      deviance, P<0.001). Because the experimental design excluded the possibility of
      physiological adaptation of the test animals to the toxicants, we conclude that
      the differences in susceptibility must have a genetic basis. Moreover, carbaryl
      tolerance levels of the populations tended to increase with increasing
      agricultural land use intensity as described by ranked percentage of land
      coverage with cereal and corn crop in the proximity of the ponds (Spearman rank
      correlation, R=0.602, P=0.066). Together, these two findings provide evidence for
      local adaptation of D. magna populations to pesticide contamination. Overall, the
      results demonstrate the potential selection pressure imposed by anthropogenic
      pollution and provide evidence that genetic erosion in natural Daphnia
      populations is related to anthropogenic impact.

PMID- 19747741
TI  - A simple method to predict impaired right ventricular performance and disease
      severity in chronic pulmonary hypertension using strain rate imaging.
AB  - BACKGROUND: The evaluation of right ventricular (RV) function is clinically
      important in pulmonary hypertension (PH) because of prognostic implications.
      Conventional echocardiography has been used to predict adverse outcomes in
      chronic PH, but there were certain limitations arising from the complexity of RV
      anatomy. We used strain rate imaging (SRI) to evaluate RV function in PH
      patients. METHODS: Study population consisted of 50 patients (mean age 46 +/- 13
      years; 39 females) with chronic PH who underwent echocardiography including SRI
      within 24h of right heart catheterization. Mean value of peak systolic
      longitudinal strain obtained from basal and mid RV free wall were calculated.
      Reduced RV systolic contraction (fractional area change <32%) and cardiac index
      (CI) <2.0 L/min/m(2) were defined as impaired RV performance. RESULTS: Pulmonary
      vascular resistance (PVR) averaged 1195 +/- 522 dyn . s . cm(-5). RV strain
      correlated closely with pulmonary artery systolic pressure (r = 0.53; p < 0.001)
      and PVR (r = 0.68; p < 0.001). RV strain best correlated with CI (r = -0.70; p <
      0.001) among the invasive variables. After adjusting for various parameters that
      could influence the CI, this correlation remained robust (r = -0.63, p < 0.001).
      In a multivariate model, RV strain (odds ratio 1.65; 95% confidential interval
      1.06-2.57; p = 0.028) was independently associated with impairment of RV
      performance. A cutoff value of -15.5% discriminated cases of impaired RV
      performance from those of preserved RV performance with a sensitivity of 100%,
      specificity of 84% and accuracy of 92%. CONCLUSIONS: RV strain correlates well
      with hemodynamic variables indicative of disease severity and help identify the
      cases of impaired RV performance in PH patients.

PMID- 19747742
TI  - Estimation of probability for the presence of claw and digital skin diseases by
      combining cow- and herd-level information using a Bayesian network.
AB  - Cross sectional data on the prevalence of claw and (inter) digital skin diseases
      on 4854 Holstein Friesian cows in 50 Danish dairy herds was used in a Bayesian
      network to create herd specific probability distributions for the presence of
      lameness causing diseases. Parity and lactation stage are identified as risk
      factors on cow level, for the prevalence of the three lameness causing diseases
      digital dermatitits, other infectious diseases and claw horn diseases. Four herd
      level risk factors have been identified; herd size, the use of footbaths, a
      grazing strategy and total mixed ration. Besides, the data has been used to
      estimate the random effect of herd on disease prevalence and to find conditional
      probabilities of cows being lame, given the presence of the three diseases. By
      considering the 50 herds representative for the Danish population, the estimates
      for risk factors, conditional probabilities and random herd effects are used to
      formulate cow-level probability distributions of disease presence in a specific
      Danish dairy herd. By step-wise inclusion of information on cow- and herd-level
      risk factors, lameness prevalence and clinical diagnosis of diseases on cows in
      the herd, the Bayesian network systematically adjusts the probability
      distributions for disease presence in the specific herd. Information on
      population-, herd- and cow-level is combined and the uncertainty in inference on
      disease probability is quantified.

PMID- 19747743
TI  - Summary receiver operating characteristics (SROC) and hierarchical SROC models
      for analysis of diagnostic test evaluations of antibody ELISAs for
      paratuberculosis.
AB  - Critical, systematic reviews of available diagnostic test evaluations are a
      meticulous approach to synthesize evidence about a diagnostic test. However,
      often the review finds that data quality is poor due to deficiencies in design
      and reporting of the test evaluations and formal statistical comparisons are
      discouraged. Even when only simple summary measures are appropriate, the strong
      correlation between sensitivity and specificity and their dependence on
      differences in diagnostic threshold across studies, creates the need for tools to
      summarise properties of the diagnostic test under investigation. This study
      presents summary receiver operating characteristics (SROC) analysis as a means to
      synthesize information from diagnostic test evaluation studies. Using data from a
      review of diagnostic tests for ante mortem diagnosis of paratuberculosis as an
      illustration, SROC and hierarchical SROC (HSROC) analysis were used to estimate
      overall diagnostic accuracies of antibody ELISAs for bovine paratuberculosis
      while accounting for covariates: the target condition (infectious or infected)
      used in the test evaluation (one for the evaluation of Se and one for Sp); and
      the type of test (serum vs. milk). The methods gave comparable results (regarding
      the estimated diagnostic log odds ratio), considering the small sample size and
      the quality of data. The SROC analysis found a difference in the performance of
      tests when the target condition for evaluation of Se was infected rather than
      infectious, suggesting that ELISAs are not suitable for detecting infected
      cattle. However, the SROC model does not take differences in sample size between
      study units into account, whereas the HSROC allows for both between and within
      study variation. Considering the small sample size, more credibility should be
      given to the results of the HSROC. For both methods the area under the (H)SROC
      curve was calculated and results were comparable. The conclusion is that while
      the SROC is simpler and easier to implement, analyse and interpret, the HSROC
      does have properties encourage the extra effort involved in the analysis.

PMID- 19747744
TI  - Double blind randomized phase II study with radiation+5-fluorouracil+/-celecoxib
      for resectable rectal cancer.
AB  - PURPOSE: To assess the feasibility and efficacy of the COX-2 inhibitor celecoxib
      in conjunction with preoperative chemoradiation for patients with locally
      advanced rectal cancer in a double blind randomized phase II study. MATERIALS AND
      METHODS: Thirty-five patients of the initially planned 80 patients with locally
      advanced rectal cancer were treated with preoperative radiation (45 Gy; 1.8
      Gy/fraction, 5 days/week) combined with 5-fluorouracil (continuous infusion, 225
      mg/m(2)/day) and celecoxib (2 x 400 mg/day) or placebo. Pathological response and
      toxicity of study treatment were evaluated, as well as expression of COX-2 and
      Ki67 in tumor tissue and IL-6 in plasma as possible molecular correlates and
      predictors of response to treatment. RESULTS: Patients treated with celecoxib
      tended to show a better response (61%) when compared to those treated with
      placebo (35%), although not significant (p=0.13). T-downstaging and N-downstaging
      were also slightly higher with celecoxib. Plasma IL-6 levels and intratumoral
      COX2 or Ki67 were altered by chemoradiation, but were not further altered by
      celecoxib treatment and therefore not useful for prediction of treatment benefit.
      Celecoxib therapy in conjunction with chemoradiation was not associated with
      additional toxicity and seemed to help mitigate therapy-related pain.
      CONCLUSIONS: Addition of celecoxib to preoperative chemoradiation is feasible for
      patients with locally advanced rectal cancer. To study the individual effect of
      COX-2 inhibitors on pathological response phase III studies are required.

PMID- 19747745
TI  - Reduced risk of head and neck second primary tumors after radiotherapy.
AB  - BACKGROUND AND PURPOSE: With radiotherapy of primary tumors of the head and neck,
      a significant dose reaches the surrounding mucosa. The field cancerization and
      second field tumor theories state that premalignant lesions are present in the
      mucosa even at the time of primary tumor treatment. We tested the hypothesis that
      exposure to irradiation stabilizes subclinical premalignant lesions. This would
      reduce the rate of second primary tumors in the upper aerodigestive tract (UADT).
      MATERIALS AND METHODS: The cohort consisted of 346 patients treated for small
      localized squamous cell carcinoma of the oral cavity (T1-2, N0, and M0). The rate
      of UADT second primary tumors was compared between 247 patients exposed to
      radiation (case subjects) and 99 patients unexposed to radiation (control
      subjects). RESULTS: Median time to UADT second primary tumor was 8.6 years for
      irradiated patients and 3.9 years for controls (p=0.007). Through the first 5
      years after the treatment of the primary tumor, the relative risk of developing a
      new UADT tumor for irradiated patients compared to controls was 0.12 (p<0.001).
      After 5 years the risk increased for irradiated cases. A corresponding change in
      risk was not found for controls. CONCLUSIONS: A slower rate of second primary
      tumors was seen within UADT mucosa exposed to irradiation. This could suggest a
      preventive effect by radiation on malignant transformation of subclinical
      premalignant foci.

PMID- 19747746
TI  - DCEMRI of spontaneous canine tumors during fractionated radiotherapy: a
      pharmacokinetic analysis.
AB  - PURPOSE: To estimate pharmacokinetic parameters from dynamic contrast-enhanced
      magnetic resonance (DCEMR) images of spontaneous canine tumors taken during the
      course of fractionated radiotherapy, and to quantify treatment-induced changes in
      these parameters. MATERIALS AND METHODS: Six dogs with tumors in the oral or
      nasal cavity received fractionated conformal radiotherapy with 54 Gy given in 18
      fractions. T(1)-weighted DCEMR imaging was performed prior to each treatment
      fraction. Time-intensity curves in the tumor were extracted voxel-by-voxel, and
      were fitted to the Brix pharmacokinetic model. The dependence of the
      pharmacokinetic parameters on the accumulated radiation dose was calculated.
      RESULTS: The Brix model reproduced the time-intensity curves well. A reduction in
      the k(ep) parameter with accumulated radiation dose was found for five (three
      significant) out of six cases, while the results for the A parameter were less
      consistent. Both pre-treatment k(ep) and the change in k(ep) with accumulated
      dose correlated significantly with tumor regression. CONCLUSIONS: Pharmacokinetic
      parameters derived from DCEMR images taken during fractionated radiotherapy may
      predict response to radiotherapy. This may potentially impact on patient
      stratification and monitoring of treatment response for image-guided treatment
      strategies.

PMID- 19747747
TI  - Low plasma adiponectin level, white blood cell count and Helicobacter pylori
      titre independently predict abnormal pancreatic beta-cell function.
AB  - Adiponectin is an adipocytokine with insulin sensitizing effect while chronic
      inflammation damages pancreatic beta-cells leading to reduced insulin response.
      We aimed to prove the hypothesis that adiponectin levels and inflammatory markers
      (white blood cell counts [WCC], Helicobacter pylori [HP] titers, high sensitivity
      C-reactive protein [hs-CRP]) may interact to affect risk of diabetes. We studied
      288 Chinese men (age-median: 41.0 years, IQR: 35.3-46.0 years) being recruited
      from the community in Hong Kong. The mean adiponectin level was 5.39+/-2.81
      microg/ml and 40.9% (n=107) had low adiponectin level (<4 microg/ml). On multiple
      regression analysis, adiponectin was negatively associated with diabetes, HOMA
      insulin resistance top quartile, plasma glucose (PG) and 2h insulin; and
      positively associated with HOMA insulin sensitivity index. WCC was independently
      associated with PG and 15' insulin, and negatively associated with HOMA insulin
      sensitivity top quartile. HP titre was associated with 30' PG level and diabetes.
      hs-CRP did not enter the multivariable model. In conclusion, adiponectin, WCC and
      HP titer are independent predictors for hyperglycemia and reduced insulin
      sensitivity in Chinese men. These findings may explain the high risk for diabetes
      in Chinese population despite their relatively low adiposity.

PMID- 19747748
TI  - Fasting plasma glucose variability as a marker of nocturnal hypoglycemia in
      diabetes: evidence from the PREDICTIVE study.
AB  - The relationship between fasting glucose (FG) variability and nocturnal
      hypoglycemia was assessed using longitudinal data from PREDICTIVE, the large
      scale observational study of insulin detemir. An HbA(1c)-corrected correlation
      was found between these endpoints, suggesting FG variability can serve as a
      useful marker for this risk in clinical practice.

PMID- 19747749
TI  - Risk factors for early and late recurrence in hepatitis B-related hepatocellular
      carcinoma.
AB  - BACKGROUND/AIMS: Hepatitis B virus (HBV) levels correlate with the development of
      hepatocellular carcinoma (HCC), but the role of viral load in HCC recurrence
      after tumor resection remains unclear. Herein we aimed to investigate the role of
      viral load in HCC recurrence following tumor resection. METHODS: From 1990 to
      2002, 193 HBV-related HCC patients who underwent tumor resection in Taipei
      Veterans General Hospital were enrolled. Serum HBV DNA level and mutations were
      analyzed for association with early and late recurrence, together with other
      clinical variables. RESULTS: During a follow-up of 58.2+/-44 months, 134 patients
      had HCC recurrence. Multivariate analysis showed that multinodularity (Hazard
      ratio [HR], 95% confidence interval [CI]; 2.232, 1.021-4.878), macroscopic venous
      invasion (4.693, 1.645-13.391), AFP >20 ng/ml (3.891, 1.795-8.475), and cut
      margin <or= 1cm (3.333, 1.487-7.470) were correlated with early recurrence
      (within two years of operation) of HCC. In addition, multivariate analysis
      determined that Ishak hepatic inflammatory activity >6 (4.658, 1.970-11.017),
      multinodularity (3.266, 1.417-7.526), ICG-15 >10% (2.487, 1.095-5.650) and HBV
      DNA level >10(6) copies/ml (2.548, 1.040-6.240) were significantly associated
      with late recurrence (>two years after resection). Patients with high viral loads
      tended to have higher Ishak inflammatory (7.00+/-3.07 vs. 5.33+/-2.96, p=0.001)
      and fibrosis scores (4.17+/-2.01 vs. 3.20+/-2.41, p=0.007) than those with lower
      loads. CONCLUSIONS: Tumor factors were associated with early HCC recurrence while
      high viral loads and hepatic inflammatory activity were associated with late
      recurrence. Pre- and post-operative antiviral and anti-inflammatory therapies may
      be crucial in reducing late recurrence.

PMID- 19747750
TI  - Pathological confirmation of primary lung cancer following breast cancer.
AB  - PURPOSE: Studies have shown that women who survive breast cancer have an
      increased risk of a future primary lung cancer, though many are based only on
      data recorded in tumor registries and none have conducted pathological
      confirmation. Previous studies and future use of large registries may be affected
      by misdiagnosis. METHODS: Pathological analysis was conducted on tumors from 110
      women with breast cancer followed by lung cancer using morphology, Estrogen
      Receptor-alpha (ER), and Thyroid Transcription Factor-1 (TTF1). We developed an
      algorithm to classify lung tumors as unlikely lung cancer (score=1) to likely
      lung cancer (score=5). RESULTS: Mean time to diagnosis of lung cancer after
      breast cancer was 13 years. 76% of breast tumors and 20% of lung tumors were
      positive for ER and 51% of lung tumors were positive for TTF-1. 86% of the lung
      tumors were probable primaries, 7% were probable metastases from the breast, and
      7% were of undetermined status. 70% of probable metastases had a latency of
      longer than 10 years. CONCLUSION: Prior studies identifying the association of
      breast cancer and breast cancer treatments with lung cancer are likely to reflect
      true associations not confounded by misdiagnosis, as evidenced by the low rate of
      misclassification detected in this study. Analysis of the years of diagnosis
      suggests that latency may not be an accurate criterion for assignment of primary
      status, which could be significant in a clinical setting. These data may also
      benefit future retrospective studies using large registries.

PMID- 19747752
TI  - Educating junior doctors on healthcare-associated infection: more work to be
      done.

PMID- 19747753
TI  - Synthesis and antimalarial activity of new atovaquone derivatives.
AB  - In this paper we describe the design and synthesis of 18 derivatives of the
      antimicrobial atovaquone which were substituted at the 3-hydroxy group by ester
      and ether functions. The compounds were evaluated in vitro for their activity
      against the growth of Plasmodium falciparum, the malaria causing parasite. All
      the compounds showed potent activity, with IC(50) values in the range of 1.25-50
      nM, comparable to those of atovaquone and much higher than chloroquine or
      quinine.

PMID- 19747755
TI  - Why doctors choose small towns: a developmental model of rural physician
      recruitment and retention.
AB  - Shortages of health care professionals have plagued rural areas of the USA for
      more than a century. Programs to alleviate them have met with limited success.
      These programs generally focus on factors that affect recruitment and retention,
      with the supposition that poor recruitment drives most shortages. The strongest
      known influence on rural physician recruitment is a "rural upbringing," but
      little is known about how this childhood experience promotes a return to rural
      areas, or how non-rural physicians choose rural practice without such an
      upbringing. Less is known about how rural upbringing affects retention. Through
      twenty-two in-depth, semi-structured interviews with both rural- and urban-raised
      physicians in northeastern California and northwestern Nevada, this study
      investigates practice location choice over the life course, describing a
      progression of events and experiences important to rural practice choice and
      retention in both groups. Study results suggest that rural exposure via
      education, recreation, or upbringing facilitates future rural practice through
      four major pathways. Desires for familiarity, sense of place, community
      involvement, and self-actualization were the major motivations for initial and
      continuing small-town residence choice. A history of strong community or
      geographic ties, either urban or rural, also encouraged initial rural practice.
      Finally, prior resilience under adverse circumstances was predictive of continued
      retention in the face of adversity. Physicians' decisions to stay or leave
      exhibited a cost-benefit pattern once their basic needs were met. These results
      support a focus on recruitment of both rural-raised and community-oriented
      applicants to medical school, residency, and rural practice. Local mentorship and
      "place-specific education" can support the integration of new rural physicians by
      promoting self-actualization, community integration, sense of place, and
      resilience. Health policy efforts to improve the physician workforce must address
      these complexities in order to support the variety of physicians who choose and
      remain in rural practice.

PMID- 19747756
TI  - The European perinatal health report: delivering comparable data for examining
      differences in maternal and infant health.
AB  - In December 2008, the first-ever European Perinatal Health Report was released by
      EURO-PERISTAT. Part of the EU Health Programme for health surveillance and
      reporting, this landmark report presents indicators of perinatal health and care
      derived from routine statistical data in 25 EU Member States and Norway. It also
      includes chapters from three other European projects with perinatal data: SCPE on
      cerebral palsy, EUROCAT on congenital anomalies and EURONEOSTAT on very preterm
      babies admitted to intensive care.

PMID- 19747757
TI  - Performance and cost analysis of Siriraj liquid-based cytology: a direct-to-vial
      study.
AB  - OBJECTIVE: To compare the cytological diagnoses, specimen adequacy, and cost of
      the Siriraj liquid-based cytology (LBC) with those of the conventional smear
      technique. STUDY DESIGN: An observational study with historical comparison was
      conducted in a tertiary university hospital. Cytological reports of 23,676
      Siriraj-LBC specimens obtained in 2006 were compared with those of 25,510
      conventional smears obtained in 2004. RESULTS: Overall prevalence of abnormal
      cervical cytology detected by conventional smear was 1.76% and by Siriraj-LBC was
      3.70%. Compared with the conventional method, the Siriraj-LBC yielded a
      significantly higher overall detection rate of abnormal cervical cytology, with a
      110.23% increase in the detection rate (P<0.001), mainly due to the increase in
      diagnosis of squamous intraepithelial lesions (SIL), both low and high grade,
      together with atypical squamous cells of undetermined significance, "atypical
      squamous cells cannot exclude HSIL", and malignancies, but not atypical glandular
      cells. The Siriraj-LBC had a smaller proportion of unsatisfactory slides (4.94%
      vs. 18.60%, P<0.001) and a higher negative predictive value (96.33% vs. 92.74%,
      P=0.001), but no difference in positive predictive value (83.03% vs. 86.83%,
      P=0.285). The cost of Siriraj-LBC was approximately 67% higher than that of the
      conventional cytology used in Siriraj Hospital and 50-70% lower than that of the
      commercially available LBC techniques in Thailand. CONCLUSION: The Siriraj-LBC
      increases the detection rate of abnormal cytology, improves specimen adequacy,
      and enhances the negative predictive value without compromising the positive
      predictive value. For centers where conventional Pap smear does not perform well,
      the introduction of a low cost Siriraj-LBC might help to improve performance and
      it may be an economical alternative to the commercially available liquid-based
      cytology.

PMID- 19747758
TI  - The value of serial cervical length measurements for the prediction of threatened
      preterm labour.
AB  - OBJECTIVES: To assess the predictive performance of cervical length measurement
      at presentation and 24h later in women with symptoms of preterm labour. STUDY
      DESIGN: Cervical length was measured transvaginally at presentation and 24 hours
      later in 122 women presenting with threatened preterm labour between 23 and 33+6
      gestational weeks. RESULTS: Six women delivered within 1 week of presentation.
      The sensitivity and specificity of a cervical length <15 mm at admission for
      delivery within one week was 83.3 and 95.8%, respectively. A reduction of >20% in
      cervical length 24h after admission predicted 50% of preterm deliveries within 1
      week, with a specificity of 92.7%; in combination with cervical length at
      presentation it did not improve the prediction. The same was observed for birth
      before 32 weeks (N=9) and birth before 35 weeks (N=15). CONCLUSIONS: Women with
      threatened preterm labour and a cervical length of <15 mm at presentation are at
      high risk of delivering preterm. Cervical change in the following 24 hours does
      not seem to improve the prediction.

PMID- 19747759
TI  - Editorial comment on: inflammatory protein serum amyloid A1 marks a subset of
      conventional renal cell carcinomas with fatal outcome.

PMID- 19747760
TI  - Males slings: compressive versus repositioning.

PMID- 19747761
TI  - Inflammatory protein serum amyloid A1 marks a subset of conventional renal cell
      carcinomas with fatal outcome.
AB  - BACKGROUND: Conventional renal cell carcinoma (RCC) is the most common renal
      cancer. As the metastatic conventional RCC is practically incurable, there is a
      need for markers to estimate the tumour aggressiveness. OBJECTIVE: To identify
      and characterise new marker(s) associated with the poor prognosis of conventional
      RCC. DESIGN, SETTING, AND PARTICIPANTS: RNA from 24 conventional RCCs was
      analysed for global gene expression by Affymetrix U133 Plus 2.0 arrays. Tissue
      microarrays containing 224 renal tumours including 87 conventional RCCs were used
      for immunohistochemistry. Cell lines HD2, HD48, HA344 and HA465 established in
      our laboratory were used for invasion assay and zymography. MEASUREMENTS: Serum
      amyloid A 1 (SAA1) was found to be upregulated in conventional RCCs and it has
      been analysed by quantitative RT-PCR and immunohistochemistry on TMAs to
      establish the correlation between SAA1 protein expression and patient survival by
      uni and multivariate analysis. The effect of SAA1 on tumour cell behaviour in
      vitro has also been examined by invasion assay and zymography. RESULTS AND
      LIMITATIONS: SAA1 RNA is expressed in conventional RCC samples of patients with
      poor prognosis. Immunohistochemistry of 72 conventional RCCs with a 5 yr follow
      up showed a correlation between SAA1 expression and the clinical outcome of
      disease. Stimulation of conventional RCC cell lines with recombinant SAA1
      increased the expression of metalloproteinase (MMP)-9 and the invasive potential
      of tumour cells. Limitation of the study is a relatively small number (72) of
      patients having follow up. CONCLUSION: SAA1 seems to be a useful marker to
      estimate the prognosis of conventional RCCs.

PMID- 19747762
TI  - Re: Luca Cindolo, Stefano Gidaro, Fabiola R. Tamburro, Luigi Schips. Laparo
      endoscopic single-site left transperitoneal adrenalectomy. Eur Urol 2010;57:911
      4.

PMID- 19747764
TI  - Editorial comment on: human prostate fibroblasts induce growth and confer
      castration resistance and metastatic potential in LNCaP cells.

PMID- 19747763
TI  - Human prostate fibroblasts induce growth and confer castration resistance and
      metastatic potential in LNCaP Cells.
AB  - BACKGROUND: The tumor microenvironment is important for progressive and
      metastatic disease. OBJECTIVE: To study the hypothesis that prostate fibroblasts
      have differential ability to induce castration-resistant prostate cancer (PCa)
      and metastatic progression and whether this effect might vary depending on the
      zonal origin of the fibroblast. DESIGN, SETTING, AND PARTICIPANTS: Human prostate
      fibroblasts from the peripheral (PZ), transition (TZ) and central (CZ) zones of
      radical prostatectomy specimens (n=13) were isolated and compared for their
      ability to promote androgen independence and metastatic progression in androgen
      responsive PCa lymph node carcinoma of the prostate (LNCaP) cells in vivo.
      INTERVENTIONS: By coinoculating marginally tumorigenic LNCaP cells with PZ or TZ
      and by altering host hormonal milieu, a series of tumorigenic and metastatic
      LNCaP epithelial sublines-P4, P4-2 (derivatives from interaction with PZ), T4,
      and T4-2 (derivatives from interaction with TZ)-were established and
      characterized. MEASUREMENTS: In vivo and in vitro evaluation of induction of
      tumor growth and metastatic potential. RESULTS AND LIMITATIONS: 1) LNCaP sublines
      were permanently altered in their cytogenetic and biologic profiles after
      cellular interaction with prostate stromal fibroblasts. LNCaP sublines grew
      faster under anchorage-dependent and -independent conditions, expressed 1-12-fold
      more prostate-specific antigen in vitro than LNCaP cells, and gained metastatic
      potential; 2) zonal differences of stromal fibroblasts in their ability to induce
      the growth and progression of LNCaP tumors as xenografts in mice may exist but
      need further analysis; 3) PZ-conditioned medium induced more anchorage
      independent growth of LNCaP cells in vitro. TZ had a higher growth rate and were
      more sensitive to dihydrotestosterone. CONCLUSIONS: We demonstrate that prostate
      fibroblasts have growth inductive potential on PCa cells and affect their
      subsequent progression to castration resistance and development of a metastatic
      phenotype.

PMID- 19747765
TI  - Intraoperative indocyanine green angiography in intracranial aneurysm surgery:
      Microsurgical clipping and revascularization.
AB  - BACKGROUND: The goal of this report is to illustrate the use of intraoperative
      indocyanine green (ICG) angiography in the surgical management of intracranial
      aneurysms, including microsurgical clipping and revascularization. METHODS: This
      study included a series of 45 patients who were surgically treated between June
      2007 and May 2008 for intracranial aneurysms. Fourty-three of the patients had
      anterior circulation aneurysms, and 2 had posterior circulation aneurysms. Forty
      one patients were treated with microsurgical clipping. Four patients underwent
      revascularization combined with aneurysm dissection or trapping. Intraoperative
      ICG angiography was used to visualize the aneurysm clipping, patency of parent
      artery or graft. The ICG angiography technique is described, with particular
      reference to evaluation of the aneurysm clipping and revascularization. RESULTS:
      Eighty-nine ICG angiography procedures were performed in 45 patients with
      intracranial aneurysms. The aneurysms were completely obliterated for all
      patients, and the grafts were patented for all except 1 patient. Pre-clipping ICG
      angiography showed the relationship of aneurysm and its parent artery clearly.
      After aneurysms being clipped, intraoperative ICG angiography found remnant of
      aneurysms, stenosis or occlusion of parent arteries and grafts in 8 cases, which
      were revised in the same surgical procedure. The results of ICG angiography
      correlated well with postoperative DSA in 97% patients. CONCLUSION: ICG
      angiography can provide real-time information and guide revision in the same
      surgical procedure for the management of intracranial aneurysms.

PMID- 19747766
TI  - CSF tau protein is a useful marker for effective treatment of superficial
      siderosis of the central nervous system: two case reports.
AB  - We report two cases of superficial siderosis (SS) of the central nervous system
      (CNS), which is caused by chronic haemorrhaging into the subarachnoid space with
      haemosiderin deposition in the superficial portion of the CNS. Patient 1 had
      fluid collection in the spinal canal, which was reported as the source of the
      chronic bleeding. Patient 2 was bleeding from thickened dura at the level of the
      sacral vertebrae. Both of the patients had xanthochromic cerebrospinal fluid. We
      surgically repaired the sources of bleeding. Subsequently the cerebrospinal fluid
      (CSF) cleared and their symptoms were not aggravated for about 1 year. We
      measured several CSF markers of SS before and after surgery. Total tau protein
      (CSF-t-tau), phosphorylated tau protein (CSF-p-tau), iron (CSF-iron) and ferritin
      (CSF-ferritin) in the CSF were highly elevated at diagnosis. After surgery, the
      levels of CSF-t-tau and CSF-p-tau were markedly reduced while CSF-iron and CSF
      ferritin had not decreased. It is suggested that CSF-t-tau and CSF-p-tau
      reflected the neural damage in SS and were useful to evaluate the effectiveness
      of SS therapies.

PMID- 19747767
TI  - Transient ischemic attack associated with stenosis of accessory middle cerebral
      artery.
AB  - Establishing the mechanism of ischemia in patients with cerebrovascular ischemia
      is important in determining prognosis as well as the therapeutic approach.
      Recurrent transient ischemic attacks in a patient with accessory middle cerebral
      artery described by Gao et al. pose important questions. The underlying
      mechanisms responsible for cerebral ischemia remain unclear. I propose some of
      the possible methods to elucidate the pathogenic mechanisms for optimization of
      treatment and secondary prevention.

PMID- 19747768
TI  - Expression of sulfotransferases and sulfatases in human breast cancer: impact on
      resveratrol metabolism.
AB  - Resveratrol is a naturally occurring anticancer compound present in grapes and
      wine that undergoes pronounced metabolism in human intestine and liver. In order
      to determine whether resveratrol is also bio-transformed in human breast
      carcinoma, metabolism experiments were conducted in breast tumor and adjacent non
      tumorous specimens from 13 patients. Resveratrol was metabolized in cytosolic
      tissue fractions to resveratrol-3-O-sulfate: the formation rates were up to 33.5
      fold higher in cancer samples than in peritumoral tissue. Further quantitative
      real-time RT-PCR analysis revealed similar expression of sulfotransferases
      SULT1A2, 1A3, and 1E1 in the paired control and tumor tissues. Sulfotransferase
      SULT1A1 expression was below the detection limit in all samples. Interestingly,
      mRNA expression of steroid sulfatase STS, but not of arylsulfatases ARS-A and ARS
      B, was significantly higher (p<0.0017) in non-malignant specimens than in tumor
      tissue samples, which might explain the higher resveratrol-3-O-sulfate
      concentrations in breast cancer specimens. Cellular localization of SULT1A3 and
      STS was also assessed by indirect immunofluorescence on paraffin-embedded
      sections from control and malignant breast tissue clearly showing a correlation
      of qRT-PCR data with protein expression of these two enzymes. Our data elucidate
      the metabolism of resveratrol in malignant and non-malignant breast tissue, which
      must be considered in humans after oral uptake of dietary resveratrol as a
      chemopreventive agent.

PMID- 19747769
TI  - Chemopreventive effects of 13alpha,14alpha-epoxy-3beta-methoxyserratan-21beta-ol
      (PJJ-34), a serratane-type triterpenoid, in a rat multi-organ carcinogenesis
      bioassay.
AB  - A novel serratane-type triterpenoid, 13alpha,14alpha-epoxy-3beta-methoxyserratan
      21beta-ol (PJJ-34) derived from cuticles of Picea jezoensis Carr. var. jezoensis,
      has proved to be highly effective at suppressing carcinogenesis both in vitro and
      in vivo. To investigate possible anti-carcinogenic efficacy at the whole-body
      level, male Fischer 344 rats were subjected to an established rat multi-organ
      carcinogenesis bioassay (DMBDD model). After initiation with five carcinogens,
      groups 1-3 (20 in each) were intragastrically (i.g.) administered PJJ-34
      dissolved in 1 ml of 0.5% CMC (5 times/week) at doses of 0, 5 and 10mg/kg body
      weight (b.w.), respectively, until the end of week 30. PJJ-34 did not show
      apparent toxicity. Incidences of adenomas (100-->75%) and carcinomas (63-->30%)
      in the lung were significantly decreased in the 5mg/kg b.w. group, and
      multiplicity of alveolar hyperplasias and total lung tumors (adenomas+carcinomas)
      were significantly reduced by both 5 and 10mg/kg. The incidence of colorectal
      tumors was also significantly decreased in the 10mg/kg group (63-->28%) along
      with the multiplicity. Rat liver pre-neoplastic lesions, glutathione S
      transferase placental form (GST-P) foci, and tumor development in the other
      organs were not affected. Immunohistochemical indices for proliferating cell
      nuclear antigen (PCNA) and cyclin D1 in normal alveolar epithelium of the lung
      were significantly suppressed at both doses. In conclusion, PJJ-34 is
      chemopreventive against lung and colon carcinogenesis without exerting apparent
      toxicity, and suppression of cell proliferation could play a key role in the
      underlying mechanisms.

PMID- 19747770
TI  - Sorption of polycyclic aromatic hydrocarbons on particulate organic matters.
AB  - Particulate organic matter (POM) is a key organic matter fraction which can
      influence soil fertility. Its interactions with hydrophobic organic pollutants
      (HOCs) have not been characterized and the mechanisms of retention of HOCs by POM
      remain unclear. In the present study, sorption behaviors of polycyclic aromatic
      hydrocarbons (PAHs) naphthalene (NAP), phenanthrene (PHE), and pyrene (PYR) by
      POMs separated from different soils were examined and the POMs were characterized
      by elemental analysis, solid state (13)C NMR, and Fourier transform infrared
      spectroscopy (FT-IR). The results indicated that POMs were mainly composed of
      aliphatic components with high polarity. The different original POMs showed
      similar chemical composition and configuration. Sorption behaviors of PAHs
      indicated that there was no significant difference in sorption capacity among the
      POMs. Sorption of NAP and PHE by POMs displayed a nonlinear isotherm, while
      sorption of PYR yielded a linear isotherm. No significant hysteresis and ionic
      strength effect were observed for PAH desorption from the POMs.

PMID- 19747771
TI  - Energy and electrode consumption analysis of electrocoagulation for the removal
      of arsenic from underground water.
AB  - A systematic study of the effect of design and operation conditions of an
      electrochemical reactor on the treatment time for arsenic (As) electro-removal
      from underground water (GW) was carried out to analyse the energy and electrode
      consumption. The effects of four factors--current density, interelectrode
      distance, electrode area-volume ratio, and liquid motion driving mode--were
      evaluated. The response variables were the energy and the electrode consumption
      and the treatment time to reduce the GW residual As concentration to 10 microg L(
      1), which is the maximum contaminant level (MCL) established by the World Health
      Organization (WHO) in drinking water. The results obtained in this study showed
      that the factor that had the greatest effect on most of the response variables
      was the liquid motion driving mode. The best residence time was 20s, which
      favoured low energy consumption (58.78 Wh m(-3)) and low electrode material loss
      (9.59 g m(-3)).

PMID- 19747772
TI  - Numerical prediction of steady-state detonation properties of condensed-phase
      explosives.
AB  - Within the scope of this study, a computer code named BARUT-X has been developed
      to calculate the detonation properties of C-H-N-O based condensed-phase
      explosives using the Chapman-Jouguet (C-J) theory. Determination of the
      detonation properties is performed in chemical equilibrium and steady-state
      conditions. Unlike other codes in the literature which use steepest descent
      optimization method, BARUT-X uses a nonlinear optimization code based on
      Generalized Reduced Gradient algorithm to compute the equilibrium composition of
      the detonation products. This optimization code provides a higher level of
      robustness of the solutions and global optimum determination efficiency. The
      Becker-Kistiakowsky-Wilson's (BKW) equation of state (EOS) is applied to the high
      density gaseous detonation products at high pressures. BARUT-X uses RDX, TNT,
      BKWR, and BKWN set of constants in the BKW EOS. In addition, the Cowan-Fickett's
      EOS is applied for the compressible solid carbon in the detonation products. The
      calculated detonation properties for several condensed-phase explosives by BARUT
      X have been compared with those computed by EXPLO5 and FORTRAN BKW codes as well
      as the experimental data in terms of detonation velocity and detonation pressure.
      Satisfactory agreement is obtained from these comparisons.

PMID- 19747773
TI  - Performance of phosphoric acid activated montmorillonite as buffer materials for
      radioactive waste repository.
AB  - In this study, the performance of phosphoric acid activated montmorillonite
      (PAmmt) was evaluated by cesium ions adsorption experiments. The PAmmt samples
      were obtained by activating with 1, 3 and 5 mol L(-1) of phosphoric acid,
      respectively under reflux for 3, 12, and 24h. Experimental results demonstrated
      that the treatment of raw K-10 montmorillonite with phosphoric acid increased the
      materials' affinity for Cs uptake and no significant amount of suspension solids
      were produced. A relatively insignificant variation in the CEC value was
      observed. Furthermore, PAmmt also showed high adsorption selectivity toward Cs
      ions. The improved sorptive properties were mainly related to the increased
      surface area and the relatively higher surface charge density. Increased specific
      surface area was the resulted from partial decomposition of lamellar structure of
      mmt; while the higher surface charge density was caused by the protonation of
      octahedral Al-OH sites during the acid activation. Generally speaking, stronger
      acid concentration and longer activation times would produce relatively more
      decomposed PAmmt particles. However, as the activation exceeds 3h, the
      precipitation of Si(4+) would passivate PAmmt against further acid attacks. Based
      upon our results, acid activation by phosphoric acid could produce PAmmt samples
      with high sorption capacity and selectivity, and good structural integrity, which
      are beneficial to be used at radioactive waste repository.

PMID- 19747774
TI  - Impact of cadmium on the bacterial communities in the gut of Metaphire posthuma.
AB  - The effects of cadmium (Cd) contamination in soil onto the bacterial communities
      of the guts pooled from ten Metaphire posthuma were addressed during 14 days'
      incubation. We found that about 50% of Cd (5mg/kg, dry weight soil) in the
      contaminated soil was bio-accumulated into the earthworms. DNA was extracted from
      the guts of M. posthuma and their dwelling soil irrespective of Cd treatment for
      the analysis of the bacterial communities of guts in M. posthuma and in soil by
      PCR-DGGE (polymerase chain reaction-denaturing gradient gel electrophoresis). A
      distinctive cluster of bacterial communities of the guts in the earthworm with
      and without Cd treatment using the analysis of unweighted pair-group method using
      arithmetic averages (UPGMA) was observed, indicating that the bacterial community
      of guts could be changed by Cd. However, no differences in the bacterial
      communities in soil irrespective of Cd treatment were observed, which could be
      resulted from the bioremediation of Cd by earthworms leading to insignificant
      effect of Cd on bacterial communities in soil. For the sequencing of some of the
      dominant bands in the DGGE profile, Bradyrhizobium japonicum, Stenotrophomonas
      sp. D2, and Labrys, sp. CC-BB4, whose sequences display an identity of more than
      97% using blast program against a known sequence in the GeneBank database and
      Ribosomal database, were identified. Collectively, our results showed that
      earthworm treatment can decrease the concentrations of Cd in soil, and Cd cause a
      shift in the bacterial communities in the guts of M. posthuma. The application of
      M. posthuma for Cd bioremediation would be desired.

PMID- 19747775
TI  - Removal of fluoride from aqueous media by Fe3O4@Al(OH)3 magnetic nanoparticles.
AB  - A novel magnetic nanosized adsorbent using hydrous aluminum oxide embedded with
      Fe(3)O(4) nanoparticle (Fe(3)O(4)@Al(OH)(3) NPs), was prepared and applied to
      remove excessive fluoride from aqueous solution. This adsorbent combines the
      advantages of magnetic nanoparticle and hydrous aluminum oxide floc with magnetic
      separability and high affinity toward fluoride, which provides distinctive merits
      including easy preparation, high adsorption capacity, easy isolation from sample
      solutions by the application of an external magnetic field. The adsorption
      capacity calculated by Langmuir equation was 88.48 mg g(-1) at pH 6.5. Main
      factors affecting the removal of fluoride, such as solution pH, temperature,
      adsorption time, initial fluoride concentration and co-existing anions were
      investigated. The adsorption capacity increased with temperature and the kinetics
      followed a pseudo-second-order rate equation. The enthalpy change (Delta H(0))
      and entropy change (DeltaS(0)) was 6.836 kJ mol(-1) and 41.65 J mol(-1)K(-1),
      which substantiates the endothermic and spontaneous nature of the fluoride
      adsorption process. Furthermore, the residual concentration of fluoride using
      Fe(3)O(4)@Al(OH)(3) NPs as adsorbent could reach 0.3 mg L(-1) with an initial
      concentration of 20 mg L(-1), which met the standard of World Health Organization
      (WHO) norms for drinking water quality. All of the results suggested that the
      Fe(3)O(4)@Al(OH)(3) NPs with strong and specific affinity to fluoride could be
      excellent adsorbents for fluoride contaminated water treatment.

PMID- 19747776
TI  - Copper remediation by Eichhornia spp. and sulphate-reducing bacteria.
AB  - Eichhornia spp. biomass was collected from Chandola Lake, Ahmedabad, Gujarat,
      India. Point of zero charge of the biomass was pH 7.3. Flask study showed pH 5
      and 2-3h contact time as optimum conditions for copper sorption with 67.25%
      copper removal. At the end of 24h of contact time, copper removal reached to
      85.0%, from 100 ppm copper containing solution. Copper loading capacity of the
      biomass ranged between 9.9 and 28.5 mg g(-1) of biomass. To understand the
      interaction among pH, temperature, presence of nickel and zinc in the system,
      2(4) factorial experiment was performed. Under the experimental conditions pH and
      interactions between pH-nickel, temperature-pH and temperature-pH-nickel-zinc
      were found to be significant with 60-74.7% copper removal. Langmuir isotherm was
      better fit as compared to Freundlich isotherm and pseudo-second order equation
      gave R(2) of 0.999 for biosorption kinetic of Eichhornia biomass. Reactor study
      showed 90% overall copper removal from 24 L of copper containing waste studied
      and sulphate-reducing bacteria played a significant role. SEMquant element
      analysis showed increase from 41.66% to 53.93%, 1.02-19.73% and 0.0-12.39% of
      chloride, aluminium and copper respectively in the loaded biomass as compare to
      unexposed biomass.

PMID- 19747777
TI  - Spectroscopic imaging of electron energy loss spectra using ab initio data and
      function field visualization.
AB  - We have devised a technique for spectral imaging using accurate ab initio
      electron energy loss near edge structure (ELNES) data and function field
      visualization. The technique is initially applied to a planar defect model in Si
      with different ring structures and no broken bonds where experimental probes are
      severely limited. The same model with B doping is also considered. It is shown
      that specific deviations in different energy ranges of the ELNES spectra are
      correlated with different structural components of the models.

PMID- 19747778
TI  - Eimeria and Cryptosporidium in Estonian dairy farms in regard to age, species,
      and diarrhoea.
AB  - Eimeria and Cryptosporidium are among the most common bovine parasites in the
      world, but little is known about them in Estonia. Basic field research is needed
      to gain insight into pathogen dynamics, providing knowledge for veterinarians and
      research. A survey of 45 Estonian dairy farms in 15 counties was carried out
      between 2006 and 2007. Three age groups: <3, 3-12, and >12 months old animals
      were sampled. Collected faeces were examined by quantitative flotation and Ziehl
      Neelsen contrast staining, and species examined morphologically. Selected samples
      containing Cryptosporidium were additionally examined by polymerase-chain
      reaction (PCR) and sequencing to determine genotypes. Twelve species of Eimeria
      were identified, seven previously unknown in Estonia. Main species in samples
      were E. bovis (30%), E. zuernii (23%), and E. ellipsoidalis (14%). All herds were
      infected and animals aged 3-12 months were more commonly infected with Eimeria
      oocysts (63%) than any other group. Calves <3 months shed most oocyst, but high
      counts were rare. A negative association (slope=-0.16, p<0.001) was found between
      the number of animals infected with Eimeria and the age category. Cryptosporidium
      were detected in 84% of the farms, and C. andersoni and C. parvum were
      successfully identified. Though prevalences of Cryptosporidium in the age groups
      were similar to the sample prevalence (30%) an increase in the infections was
      found with increasing age (p<0.001). Higher diarrhoea scores were negatively
      associated with Eimeria spp. infection (slope=-0.08, p<0.05), whereas
      Cryptosporidium could not be associated with the presence of diarrhoea. Frequent
      low intensity infections of animals in all age groups with both parasites apply a
      constant stress on the animals with impact on health and production. The Estonian
      results are different compared to available studies in regard of: older animals
      commonly being infected, finding of modest oocyst counts, and distribution of
      Eimeria species.

PMID- 19747779
TI  - Stress amplification effect of lung.
AB  - Under a blast or impact load, rapid movement of the thoracic wall generates
      stress in lung, a foam-like structure of high compressibility, which is different
      from general solids. Due to this unique characteristic, it is hypothesized that
      when lung is subjected to a blast or impact load, there will be an initial low
      stress progressively developed into a high stress in a short duration in a thin
      layer of parenchyma at the lung surface. Compared to the incident stress, the
      actual stress value experienced by lung is amplified, which may cause alveolar
      capillary walls to burst, subsequently results in injuries such as edema or
      hemorrhage. This hypothesis can explain one significant phenomenon observed in
      animal tests that the gross thoracic compression do not cause major lung injury
      and there is a close relationship between thoracic wall velocity and the lung
      injury degree. According to the hypothesis, under a blast or impact load, there
      should be a significant injury degree discrepancy between a thin layer of
      parenchyma at the lung surface and the rest of the lung. Serious injuries should
      be mainly found in this thin layer, which can be employed to test whether this
      amplified effect exists or not. The hypothesis may shed some light on the
      mechanism of blast lung injury.

PMID- 19747780
TI  - Enhancement of noncoronary collateral circulation: the hypothesis of an
      alternative treatment for ischemic heart disease.
AB  - The internal thoracic arteries (ITAs) are a source of "noncoronary collateral
      circulation" (NCCC), or "noncoronary collateral blood flow" (NCCBF). The
      hypothesis herein is that enhancement of NCCC may represent an alternative means
      of myocardial blood supply: (1) Ligature of the ITAs creates a local hypertensive
      status and increases the perfusion pressure within the channels leading to the
      heart; (2) Myocardial ischemic stimulus diverts most ITA-related collateral flow
      to the heart rather than to the chest wall; (3) The ITAs may develop neo
      collaterals owing to their ischemia-related plastic potential; (4) Angiogenic
      growth factor administration within the ITAs enhances neo-collateral development.
      These elements may pave the way for a new field of cardiovascular research aimed
      at enhancing NCCC as a new therapeutic option for ischemic heart disease.

PMID- 19747781
TI  - Impact of high-dose chemotherapy on the ability to deliver subsequent local
      regional radiotherapy for breast cancer: analysis of Cancer and Leukemia Group B
      Protocol 9082.
AB  - PURPOSE: To report, from Cancer and Leukemia Group B Protocol 9082, the impact of
      high-dose cyclophosphamide, cisplatin, and BCNU (HD-CPB) vs. intermediate-dose
      CPB (ID-CPB) on the ability to start and complete the planned course of local
      regional radiotherapy (RT) for women with breast cancer involving >or=10 axillary
      nodes. METHODS AND MATERIALS: From 1991 to 1998, 785 patients were randomized.
      The HD-CPB and ID-CPB arms were balanced regarding patient characteristics. The
      HD-CPB and ID-CPB arms were compared on the probability of RT initiation,
      interruption, modification, or incompleteness. The impact of clinical variables
      and interactions between variables were also assessed. RESULTS: Radiotherapy was
      initiated in 82% (325 of 394) of HD-CPB vs. 92% (360 of 391) of ID-CPB patients
      (p = 0.001). On multivariate analyses, RT was less likely given to patients who
      were randomized to HD treatment (odds ratio [OR] = 0 .38, p < 0.001), older (p =
      0.005), African American (p = 0.003), postmastectomy (p = 0.02), or estrogen
      receptor positive (p = 0.03). High-dose treatment had a higher rate of RT
      interruption (21% vs. 12%, p = 0.001, OR = 2.05), modification (29% vs. 14%, p =
      0.001, OR = 2.46), and early termination of RT (9% vs. 2%, p = 0.0001, OR =
      5.35), compared with ID. CONCLUSION: Treatment arm significantly related to
      initiation, interruption, modification, and early termination of RT. Patients
      randomized to HD-CPB were less likely to initiate RT, and of those who did, they
      were more likely to have RT interrupted, modified, and terminated earlier than
      those randomized to ID-CPB. The observed lower incidence of RT usage in African
      Americans vs. non-African Americans warrants further study.

PMID- 19747782
TI  - Intensity-modulated radiotherapy optimization in a quasi-periodically deforming
      patient model.
AB  - PURPOSE: To present the implementation of a probability-based, four-dimensional
      (4D) intensity-modulated radiotherapy (IMRT) planning approach that explicitly
      optimizes the accumulated dose to moving tissue, estimated using the patient's
      probability density function (pdf) of respiratory motion. This is termed
      "optimization in tissue's-eye-view". METHODS AND MATERIALS: The method
      incorporates 4D Monte Carlo dose calculation in multiple geometries of a
      respiratory-correlated CT dataset. The instance doses are weighted according to
      the breathing pdf and accumulated in a common reference geometry, which involves
      dose warping based on deformable registration. The algorithm produces deliverable
      multileaf collimator segments and was tested on a sample lung cancer patient
      dataset with large target excursion. Accumulated doses of the moving target and
      organs at risk of this plan were compared with those of corresponding margin
      based static IMRT plans for free-breathing and gated treatment, as well as target
      tracking. RESULTS: Target tracking provided best target coverage. Both the
      presented 4D IMRT approach for free-breathing treatment and gated treatment gave
      similar results for target coverage and lung dose, with significantly better
      target coverage than the margin-based static IMRT plan for free-breathing
      treatment. CONCLUSIONS: The presented 4D planning concept offers an alternative
      to gating by providing the optimal dose for free-breathing IMRT treatment.
      Although the focus of this study was 4D lung planning, the approach can be
      generally applied for IMRT optimization in randomly deforming patient models.

PMID- 19747783
TI  - NTCP modeling of subacute/late laryngeal edema scored by fiberoptic examination.
AB  - PURPOSE: Finding best-fit parameters of normal tissue complication probability
      (NTCP) models for laryngeal edema after radiotherapy for head and neck cancer.
      METHODS AND MATERIALS: Forty-eight patients were considered for this study who
      met the following criteria: (1) grossly uninvolved larynx, (2) no prior major
      surgery except for neck dissection and tonsillectomy, (3) at least one fiberoptic
      examination of the larynx within 2 years from radiotherapy, (4) minimum follow-up
      of 15 months. Larynx dose-volume histograms (DVHs) were corrected into a linear
      quadratic equivalent one at 2 Gy/fr with alpha/beta = 3 Gy. Subacute/late edema
      was prospectively scored at each follow-up examination according to the Radiation
      Therapy Oncology Group scale. G2-G3 edema within 15 months from RT was considered
      as our endpoint. Two NTCP models were considered: (1) the Lyman model with DVH
      reduced to the equivalent uniform dose (EUD; LEUD) and (2) the Logit model with
      DVH reduced to the EUD (LOGEUD). The parameters for the models were fit to
      patient data using a maximum likelihood analysis. RESULTS: All patients had a
      minimum of 15 months follow-up (only 8/48 received concurrent chemotherapy):
      25/48 (52.1%) experienced G2-G3 edema. Both NTCP models fit well the clinical
      data: with LOGEUD the relationship between EUD and NTCP can be described with
      TD50 = 46.7 +/- 2.1 Gy, n = 1.41 +/- 0.8 and a steepness parameter k = 7.2 +/-
      2.5 Gy. Best fit parameters for LEUD are n = 1.17 +/- 0.6, m = 0.23 +/- 0.07 and
      TD50 = 47.3 +/- 2.1 Gy. CONCLUSIONS: A clear volume effect was found for edema,
      consistent with a parallel architecture of the larynx for this endpoint. On the
      basis of our findings, an EUD <30-35 Gy should drastically reduce the risk of G2
      G3 edema.

PMID- 19747784
TI  - [Risk management...in general and in obstetrics: ambition on an ambiguous
      pathway].

PMID- 19747785
TI  - Anthrax undervalued zoonosis.
AB  - Anthrax is a non-contagious disease, known since ancient times. However, it
      became a matter of global public interest after the bioterrorist attacks in the
      U.S.A. during the autumn of 2001. The concern of politicians and civil
      authorities everywhere towards this emergency necessitated a significant research
      effort and the prevention of new bioterrorist acts. Anthrax is primarily a
      disease that affects livestock and wildlife; its distribution is worldwide; and
      it can represent a danger to humans but especially more so when it occurs in
      areas considered to be free and in atypical seasons and climatic conditions. The
      atypicality of the phenomenon may lead health workers to misdiagnose and,
      consequently, an inappropriately manage of affected carcasses with a consequent
      and inevitable increase in the risk of human infection. This article emphasises
      the importance of paying increasing attention to this zoonosis. The biggest risk
      is its underestimation.

PMID- 19747786
TI  - Selection effects and database screening in forensic science.
AB  - We argue that it is, in principle, not difficult to deal with selection effects
      in forensic science. If a suspect is selected through a process that is related
      to the forensic evidence, then the strength of the evidence will be compensated
      by very small prior odds. No further correction is necessary. The same is true
      for so-called data-dependent hypotheses. These are allowed, since if the
      hypothesis is really "tailored around" the evidence, the evidential value will be
      high but the prior odds will compensate for that. The assessment of the prior
      odds is outside the scope of the forensic scientist, but he should make
      lawmakers, judges and juries aware of the phenomenon. This discussion applies to
      many situations--we discuss four concrete examples.

PMID- 19747787
TI  - [Do we really need antiflu virus medication?].

PMID- 19747789
TI  - [Abdominal bloating: an up-to-date].
AB  - Bloating is a common symptom, especially in women. In the clinical practice, it
      remains a therapeutic challenge. Since recently, its pathophysiology is better
      understood: an impaired transit of gas (particularly in the small bowel) or a
      visceral hypersensitivity leading to the induction of an abdominal discomfort
      despite a normal volume of gas are two of the main causes, far more frequent than
      an excessive production of gas. Moreover, bloating can be related to abnormal
      viscera-somatic reflexes promoting both an abdomino-phrenic dyssynergia and the
      relaxation of the muscles of the abdominal wall. From a therapeutic point of
      view, the efficacy of the gas absorbants remains to be more documented. Besides
      the treatment of a constipation and the avoidance of nutrients either highly
      fermentable or rich in fructose, other therapeutic options include prokinetics
      and drugs acting on visceral sensitivity. Probiotics are another promising
      option. In some centers, a non pharmacological therapeutic approach, mainly based
      on hypnosis, is discussed.

PMID- 19747790
TI  - [Liver transplantation in a patient with alcoholic cirrhosis: discussion about
      nonabstinence].
AB  - Liver transplantation is the recognized treatment for serious cases of alcoholic
      cirrhosis. However, due to their poor image within society, patients with
      alcoholic cirrhosis are often less referred to transplant centres. This is even
      more surprising since in terms of patient' and graft's survival, the results of
      transplantation are comparable, if not better, than in other indications.
      Transplantation is the treatment for the liver disease, not a treatment for
      alcoholism. In the case of severe alcoholic disease, a relapse is neither
      surprising nor unacceptable or insignificant if severe. In this case, it has an
      impact on the long-term survival, notably due to mortality by cancer. All the
      medical teams carrying out transplants agree that abstinence is necessary when a
      patient is being evaluated for liver transplantation. However, it is not proven
      that a set period of 6 months' abstinence prior to the transplantation can modify
      the results. The problem of alcoholism must be treated specifically in terms of
      addiction both before and after transplantation.

PMID- 19747791
TI  - Computer-aided detection (CAD) of lung nodules and small tumours on chest
      radiographs.
AB  - Detection of focal pulmonary lesions is limited by quantum and anatomic noise and
      highly influenced by variable perception capacity of the reader. Multiple studies
      have proven that lesions - missed at time of primary interpretation - were
      visible on the chest radiographs in retrospect. Computer-aided diagnosis (CAD)
      schemes do not alter the anatomic noise but aim at decreasing the intrinsic
      limitations and variations of human perception by alerting the reader to
      suspicious areas in a chest radiograph when used as a 'second reader'. Multiple
      studies have shown that the detection performance can be improved using CAD
      especially for less experienced readers at a variable amount of decreased
      specificity. There seem to be a substantial learning process for both,
      experienced and inexperienced readers, to be able to optimally differentiate
      between false positive and true positive lesions and to build up sufficient trust
      in the capabilities of these systems to be able to use them at their full
      advantage. Studies so far focussed on stand-alone performance of the CAD schemes
      to reveal the magnitude of potential impact or on retrospective evaluation of CAD
      as a second reader for selected study groups. Further research is needed to
      assess the performance of these systems in clinical routine and to determine the
      trade-off between performance increase in terms of increased sensitivity and
      decreased inter-reader variability and loss of specificity and secondary
      indicated follow-up examinations for further diagnostic workup.

PMID- 19747792
TI  - Efficacy and safety of immediate angioplasty versus ischemia-guided management
      after thrombolysis in acute myocardial infarction in areas with very long
      transfer distances results of the NORDISTEMI (NORwegian study on DIstrict
      treatment of ST-elevation myocardial infarction).
AB  - OBJECTIVES: The goal of this study was to compare a strategy of immediate
      transfer for percutaneous coronary intervention (PCI) with an ischemia-guided
      approach after thrombolysis in patients with very long transfer distances to PCI.
      BACKGROUND: Thrombolysis remains the treatment of choice in ST-segment elevation
      myocardial infarction (STEMI) when primary PCI cannot be performed within 90 to
      120 min. The optimal treatment after thrombolysis is still unclear. METHODS: A
      total of 266 patients with acute STEMI living in rural areas with more than 90
      min transfer delays to PCI were treated with tenecteplase, aspirin, enoxaparin,
      and clopidogrel and randomized to immediate transfer for PCI or to standard
      management in the local hospitals with early transfer, only if indicated for
      rescue or clinical deterioration. The primary outcome was a composite of death,
      reinfarction, stroke, or new ischemia at 12 months, and analysis was by intention
      to treat. RESULTS: The primary end point was reached in 28 patients (21%) in the
      early invasive group compared with 36 (27%) in the conservative group (hazard
      ratio: 0.72, 95% confidence interval: 0.44 to 1.18, p = 0.19). The composite of
      death, reinfarction, or stroke at 12 months was significantly reduced in the
      early invasive compared with the conservative group (6% vs. 16%, hazard ratio:
      0.36, 95% confidence interval: 0.16 to 0.81, p = 0.01). No significant
      differences in bleeding or infarct size were observed. CONCLUSIONS: Immediate
      transfer for PCI did not improve the primary outcome significantly, but reduced
      the rate of death, reinfarction, or stroke at 12 months in patients with STEMI,
      treated with thrombolysis and clopidogrel in areas with long transfer distances.
      (Norwegian Study on District Treatment of ST-Elevation Myocardial Infarction;
      NCT00161005).

PMID- 19747793
TI  - Plasma hormone and metabolite concentrations involved in the somatotropic axis of
      Japanese Black heifers in association with growth hormone gene polymorphism.
AB  - Bovine growth hormone (bGH) gene polymorphism of leucine (Leu)-threonine (Thr)
      (allele A), valine (Val)-Thr (allele B), and Val-methionine (Met) (allele C) at
      codons 127 and 172 was shown to relate with carcass trait variations in Japanese
      Black cattle. In this study, 10-mo-old Japanese Black heifers with growth hormone
      (GH) genotypes AA, AB, BB, AC, BC, and CC (N=141) were compared for basal GH,
      insulin-like growth factor-1 (IGF-1), insulin, ghrelin, glucose, and
      nonesterified fatty acid (NEFA) concentrations. Growth hormone release was also
      measured as response to growth hormone-releasing hormone (GHRH) (0.4 microg/kg
      body weight [BW]) using 18 heifers with GH genotypes AA, BB, and CC (n=6 for each
      group). The genotype AA heifers showed the greatest BW among genotypes (P<0.05).
      Genotype AC, BC, and CC heifers showed greater GH concentrations than genotype
      AA, AB, or BB heifers, in which genotype CC heifers had the highest
      concentrations (P<0.05). However, IGF-1 concentrations did not significantly
      differ. The genotype AA and BB heifers had a greater GH release at 60 min
      following GHRH injection than did the genotype CC heifers. The area under the
      curve (AUC; P<0.07) and incremental area (IA; P<0.08) of GH responses to the GHRH
      challenge tended to be the highest in the genotype AA heifers and the lowest in
      the genotype CC heifers. In conclusion, GH gene polymorphism altered GH, which
      may have contributed to differences in BW and carcass traits among genotypes.

PMID- 19747794
TI  - Editorial: the multidisciplinary team process: the next steps.

PMID- 19747795
TI  - Surgical practices for malignant left colonic obstruction in Germany.
AB  - AIM: Data from the multicentric observation study Kolon/Rektum-Karzinome
      (Primartumor) (primary colorectal carcinoma) are adduced to assess the status of
      surgical treatment of this condition in Germany and to compare different
      operative approaches in the emergency treatment of obstructive left-sided colon
      cancer, especially diversion (Hartmann's procedure) and primary anastomosis.
      PATIENTS AND METHODS: Out of 15,911 patients with cancer of the left colon,
      recorded between 01.01.2000 and 31.12.2004, a total of 743 patients underwent
      emergency surgery for an obstructive tumour, performed as a radical resection.
      These patients were compared in respect of their risk profile and postoperative
      result. RESULTS: In 57.9% (n=430) a one-stage operation (Group I), in 11.7%
      (n=87) a primary anastomosis with protective stoma (Group II), and in 30.4%
      (n=226), Hartmann's procedure (Group III) was performed. In Group III more
      patients were male, overweight and multimorbid, and more had advanced-stage
      tumours. The morbidity and hospital mortality (overall hospital mortality, 7.7%;
      n=57) did not differ significantly between the groups. The insertion of a
      protective stoma did not affect the rate of anastomotic insufficiency (Group I,
      7%; Group II, 8.0%). CONCLUSIONS: Primary anastomosis for emergency left colon
      carcinoma obstruction should only be regarded as indicated in cases where the
      risk profile is favourable. Our results suggest that in advanced obstruction and
      in high-risk cases Hartmann's procedure should be used. A protective stoma did
      not appear to confer any advantage.

PMID- 19747796
TI  - Looking beyond fear: the extinction of other emotions implicated in anxiety
      disorders.
AB  - Previous research examining anxiety has traditionally focused on models of fear.
      More recently, attention has been directed to the role of disgust as an important
      emotion in the context of certain anxiety disorders. Further, it has been
      suggested that disgust, a form of evaluative responding, may be resistant to
      extinction and may contribute to relapse. However, previous work on this has
      largely relied on self-report ratings. In the current experiment, using a disgust
      conditioning and extinction procedure, disgust reactions were indeed shown to be
      resistant to extinction, as indexed by both self-report and an objective
      behavioral measure (visual avoidance). Furthermore, our research shows that
      individuals with greater levels of disgust sensitivity exhibit heightened
      resistance to extinction. In addition, expectancy of the disgusting US during
      extinction was dissociated from measures of disgust responding. Given that the
      treatment of choice for anxiety disorders (exposure therapy) is based on models
      of extinction, this research suggests that current treatments for anxiety
      disorders may not be adequately targeting disgust reactions, a crucial
      maintaining factor in certain anxiety disorders. As such, this inattention to
      disgust reactions may reduce the effectiveness of treatment in the short-term or
      may leave the patient vulnerable to relapse in the long-term.

PMID- 19747797
TI  - Modifying interpretations among individuals high in anxiety sensitivity.
AB  - To examine the causal relationship between cognitive biases and anxiety, a bias
      modification paradigm was used to reduce negative interpretation biases in
      participants with high anxiety sensitivity (AS). Participants (N=75) were
      assigned to a Positive training condition or to one of two Control conditions
      (Neutral or No training). During training, participants imagined themselves in
      ambiguous scenarios related to AS. Positive training required participants to
      resolve the scenarios' ambiguity positively and was hypothesized to result in
      more positive and less negative subsequent interpretations related to AS, fewer
      self-reported AS symptoms, and less emotional vulnerability on AS stressors
      (compared to the Control conditions). As expected, Positive training shifted
      interpretations of novel scenarios and self-reported AS symptoms in the
      anticipated direction. Evidence was mixed for the effect of Positive training on
      emotional vulnerability (small effect for less fear, but not for avoidance).
      Findings support the causal premise underlying cognitive models of anxiety.

PMID- 19747798
TI  - A knowledge-based technique for liver segmentation in CT data.
AB  - Liver cancer is one of the major death factors in the world. Transplantation and
      tumor removal are two main therapies in common clinical practice. Both tasks need
      image assisted planning and quantitative evaluations. Automatic liver
      segmentation is required for corresponding quantitative evaluations. Conventional
      approaches in liver segmentation consist of finding the initial liver border
      followed by tuning the border to the final mask. Finding the liver initial border
      is of great importance as the latter step largely depends on the initial step. In
      the previous works, the liver initial border was determined by applying
      thresholding and morphological filters. In order to estimate the liver initial
      boundary, we have proposed a technique based on anatomical knowledge of liver,
      its surrounding tissues as well as the approach that a clinician follows in
      screening liver in a CT dataset. Based on the above reasoning, we developed a
      multi-step heuristic technique to segment liver from other tissues in multi-slice
      CT images. The proposed technique can deal with various shapes, locations, and
      liver sizes. The method was evaluated in the presence of 50 actual liver data
      sets and the results were encouraging.

PMID- 19747799
TI  - Do alterations in inter-ictal heart rate variability predict sudden unexpected
      death in epilepsy?
AB  - Reduced heart rate variability (HRV) may predispose to sudden unexpected death in
      epilepsy (SUDEP). We ascertained whether HRV predicts SUDEP in chronic epilepsy
      using a case-control design and investigated parameters of inter-ictal HRV in 14
      patients (7 had died from SUDEP). No HRV parameter was associated with SUDEP.
      Thus, although altered HRV might be involved in SUDEP, HRV parameters are not
      clear-cut predictors for SUDEP.

PMID- 19747800
TI  - Elementary neurocognitive function, learning potential and everyday life skills
      in schizophrenia: what is their relationship?
AB  - Few studies have investigated the relationships between static, elementary
      neurocognitive functions, dynamic measures of learning potential and functional
      status in schizophrenia, despite the putative role of learning potential in
      models of the relationship between static neurocognitive function and functional
      status (e.g., Green et al., 2000). The current study sought to clarify these
      relationships. One-hundred and twenty-five outpatients with schizophrenia were
      administered the California Verbal Learning Test-II (CVLT-II), as an index of
      learning potential, along with measures of sustained attention, verbal prose
      recall, working memory, problem-solving and processing speed, and a capacity
      measure of everyday life skills (Study 1). A subset of 48 outpatients with
      schizophrenia who were impaired on the Wisconsin Card Sorting Test (WCST) were
      also administered a test-train-test version of the WCST as a second measure of
      learning potential (Study 2). As expected, several static, elementary
      neurocognitive measures were linked to measures of everyday life skills in both
      samples. There was no evidence, however, that either measure of learning
      potential contributed unique variance beyond that explained by elementary
      cognitive skill to measures of everyday life skills. Learning potential was also
      tested as a mediator and moderator of the relationship between static
      neurocognitive function and measures of everyday life skills. Neither learning
      potential measure mediated the relationship between static measures of
      neurocognition and everyday life skills. Learning potential, as measured by the
      CVLT-II, was found to moderate the relationship of processing speed and everyday
      life skills. Taken together, these findings raise questions as to the explanatory
      value of measures of learning potential as predictors of functional status in
      schizophrenia.

PMID- 19747801
TI  - Lonicera caerulea and Vaccinium myrtillus fruit polyphenols protect HaCaT
      keratinocytes against UVB-induced phototoxic stress and DNA damage.
AB  - BACKGROUND: Sunlight is a very potent environmental factor in skin pathogenesis
      and can induce skin cancer. UVB irradiation is known to cause oxidative stress,
      inflammation and especially DNA damage. Topical application of agents with UV
      absorbing, antioxidant and anti-inflammatory activities is a successful strategy
      in the protection of the skin against UV-caused damage. OBJECTIVE: To examine the
      ability of the phenolic fraction of Lonicera caerulea and Vaccinum myrtillus
      fruits to moderate UVB-induced damage. METHODS: HaCaT keratinocytes, a well
      established in vitro system for investigations on UV radiation induced cell
      damage, were used to assess the effects of pre- and post-treatment with L.
      caerulea (LCE) and V. myrtillus (VME) phenolic fractions (5-50 mg/l) on
      keratinocyte damage induced by a solar simulator (295-315 nm). RESULTS: In this
      study, a model of UVB-induced damage to HaCaT was established. LCE and VME
      efficiently reduced the extent of DNA breakage (especially at concentrations of
      25 and 10 mg/l) together with caspase-3 and -9 activity and DNA laddering induced
      by UVB (100 or 200 mJ/cm(2)). LCE and VME significantly decreased RONS generation
      and partially diminished IL-6 expression. LCE pre-treatment also prevented
      keratinocytes proliferation. CONCLUSION: The results suggest that the phenolic
      fraction of L. caerulea and V. myrtillus fruits suppress UVB-caused injury to
      keratinocytes. These results now need to be demonstrated in vivo.

PMID- 19747802
TI  - [Exceptional digestive location of crystal deposits in primary hyperoxaluria].
AB  - We report 3 cases of primary oxalosis with nephrocalcinosis and severe renal
      failure. Extrarenal involvement was noted in bones in 3 cases, the heart in 2
      cases, the central nervous system in 2 cases, the skin in 1 case and the eye in 1
      case. The 3 patients presented with acute digestive disorders. Ultrasonography
      and CT scans showed digestive wall calcifications in addition to the classic
      appearance of primary oxalosis such as nephrocalcinosis or bone involvement.
      Primary hyperoxaluria is characterized by a calcium deposit in different tissues,
      mainly in kidneys. Digestive wall involvement has never been reported in the
      literature. Primary oxaluria should be considered in the presence of such a
      deposit in the gut wall.

PMID- 19747803
TI  - An NPC1L1 gene promoter variant is associated with autosomal dominant
      hypercholesterolemia.
AB  - BACKGROUND AND AIMS: A substantial number of subjects with autosomal dominant
      hypercholesterolemia (ADH) do not have LDL receptor (LDLR) or apolipoprotein B
      (APOB) mutations. Some ADH subjects appear to hyperabsorb sterols from the
      intestine, thus we hypothesized that they could have variants of the Niemann-Pick
      C1-Like 1 gene (NPC1L1). NPC1L1 encodes a crucial protein involved in intestinal
      sterol absorption. METHODS AND RESULTS: Four NPC1L1 variants (-133A>G, -18C>A,
      1679C>G, 28650A>G) were analyzed in 271 (155 women and 116 men) ADH bearers
      without mutations in LDLR or APOB aged 30-70years and 274 (180 women and 94 men)
      control subjects aged 25-65years. The AC haplotype determined by the -133A>G and 
      18C>A variants was underrepresented in ADH subjects compared to controls
      (p=0.01). In the ADH group, cholesterol absorption/synthesis markers were
      significantly lower in AC homozygotes that in all others haplotypes.
      Electrophoretic mobility shift assay (EMSA) results revealed that the -133A
      specific oligonucleotide produced a retarded band stronger than the -133G allele.
      Luciferase activity with NPC1L1 -133G variant was 2.5-fold higher than with the 
      133A variant. CONCLUSION: The -133A>G polymorphism exerts a significant effect on
      NPC1L1 promoter activity. NPC1L1 promoter variants might explain in part the
      hypercholesterolemic phenotype of some subjects with nonLDLR/nonAPOB ADH.

PMID- 19747804
TI  - Correlates of quality of life in adults with type 1 diabetes treated with
      continuous subcutaneous insulin injection.
AB  - BACKGROUND AND AIMS: Aim of this study was to identify subgroups of adults with
      Type 1 Diabetes Mellitus (T1DM) treated with Continuous Subcutaneous Insulin
      Infusion (CSII) at higher risk of poor quality of life (QoL). A sample of
      consecutive patients completed the Diabetes Specific Quality of Life Scale
      (DSQOLS), investigating the daily burden and restrictions related to diabetes.
      Lower DSQOLS scores indicate worse QoL perception. METHODS AND RESULTS: The main
      results were obtained by using a regression-tree technique (RECursive
      Partitioning and AMalgamation - RECPAM) and multivariate logistic regression.
      Overall, 472 patients aged between 18 and 55 years were recruited by 43 Italian
      centers. RECPAM analysis led to the identification of 5 classes characterized by
      a marked difference in QoL. Male patients not reporting episodes of ketoacidosis
      and using CSII for >2 years had the lowest likelihood of scoring in the lower
      tertile of the DSQOLS summary score, and thus represented the reference category.
      Patients who reported > or =1 ketoacidosis episodes (OR = 5.4; 95% CI 2.4-12.1)
      and female patients with a duration of diabetes of <10 years (OR = 5.9; 95% CI
      2.6-13.5) had the highest likelihood of reporting poor QoL, while females with
      longer diabetes duration (OR = 2.4; 95% CI 1.3-4.7) and males treated with CSII
      for < or =2 years (OR = 2.2; 95% CI 1.1-4.6) showed a two-fold risk of poor QoL.
      Patient age, diabetic complications and civil status were globally predictive
      variables associated with poor QoL. CONCLUSION: We identified subgroups of T1DM
      individuals treated with CSII showing a major impairment in QoL. Specific
      strategies are needed to help the patient cope with this therapeutic modality,
      especially during the initial phase of treatment.

PMID- 19747805
TI  - A novel component of the metabolic syndrome: the oxidative stress.
AB  - The metabolic syndrome (MS) represents a cluster of cardiovascular (CV) risk
      factors associated to CV disease and type 2 diabetes. It is still under debate
      whether MS is a mere aggregation of risk factors or it represents a clinical
      entity with visceral obesity as underlying pathophysiological trigger. The
      publication of several diagnostic criteria of MS by scientific associations or
      experts panels reflects this uncertainty in understanding the real nature of MS.
      Besides the metabolic disturbances of MS, as visceral obesity,
      hypertriglyceridemia, low HDL cholesterol, hypertension and hyperglycemia, novel
      mechanisms of arterial damage have been identified. This paper reviews the
      evidence showing that MS and MS factors are characterized by increased oxidative
      stress, a relevant factor contributing to the development of metabolic and
      cardiovascular complications. In the next future, the measure of plasma oxidative
      stress may contribute to identify a subset of MS patients at increased CV risk,
      candidates to more intensive therapies.

PMID- 19747806
TI  - Evolution of chameleon locomotion, or how to become arboreal as a reptile.
AB  - High-speed, biplanar X-ray motion analysis, X-ray reconstruction of moving
      morphology (XROMM) and morphological studies have led to the identification of
      those traits which are considered to be crucial for the evolution of arboreal
      locomotion in chameleons. The loss of the extensive lateral undulation typical of
      reptiles needs to be compensated by high mobility in the shoulder girdle and a
      clear functional regionalization of the trunk. Large limb excursion angles
      provide a compliant gait and are made possible by a functional
      parasagittalization of fore- and hind limbs, at least temporarily. All these
      evolutionary novelties parallel very similar modifications in the evolution of
      the locomotor apparatus in therian mammals. We propose that the convergent
      "invention" of dynamic stability and a compliant gait seem to be responsible for
      the locomotor similarities between chameleons and mammals.

PMID- 19747807
TI  - Preventive effect of crocin of Crocus sativus on hemodynamic, biochemical,
      histopathological and ultrastuctural alterations in isoproterenol-induced
      cardiotoxicity in rats.
AB  - We investigated the effects of crocin, a pharmacologically active constituent of
      Crocus sativus L., in isoproterenol (ISO)-induced cardiotoxicity with reference
      to hemodynamic, antioxidant, histopathological and ultrastructural parameters.
      Rats were administered crocin (5, 10 and 20mg/kg/day) or vehicle orally for 21
      days along with ISO (85mg/kg, subcutaneously, at 24h interval) on 20th and 21st
      day. On 22nd day ISO-control rats showed cardiac dysfunction as indicated by
      lowering of systolic, diastolic and mean arterial blood pressures. In addition, a
      significant decrease in maximum positive and negative rate of developed left
      ventricular pressure (+/-LVdp/dt(max)) and an increase in left ventricular end
      diastolic pressure (LVEDP) were observed. Furthermore, a marked reduction in the
      activities of myocardial creatine kinase-MB (CK-MB) isoenzyme, lactate
      dehydrogenase (LDH), superoxide dismutase (SOD), catalase (CAT), and reduced
      glutathione (GSH) levels along with an increase in content of malondialdehyde
      (MDA) were observed. Myocardial necrosis, edema and inflammation were evident
      from the light microscopic and ultrastructural changes. Crocin at the dose of
      20mg/kg/day significantly modulated hemodynamic and antioxidant derangements. The
      preventive role of crocin on ISO-induced MI was reconfirmed by histopathological
      and ultrastructural examinations. The effect at the dose of 20mg/kg/day of crocin
      was more pronounced than that of other two doses (5 and 10mg/kg/day). The results
      suggest that crocin may have cardioprotective effect in ISO-induced cardiac
      toxicity through modulation of oxidative stress in such a way that maintains the
      redox status of the cell.

PMID- 19747808
TI  - Beta-lactamase inhibitory component from the roots of Fissistigma cavaleriei.
AB  - Therapeutic control of beta-lactamase-producing bacteria has been a major
      clinical problem. Development of drug combinations containing the beta-lactamase
      inhibitors has given clinicians a novel approach to controlling resistant
      organisms. In our search for beta-lactamase inhibitors from natural resources, we
      found that the methanol extract of the roots of Fissistigma cavaleriei showed an
      inhibitory effect on beta-lactamase. Bioassay-guided isolation of the extract
      yielded an active compound that was identified as salicylsalicylic acid by
      physical and spectroscopic methods. The compound showed inhibitory effects on
      beta-lactamase in a dose-dependent manner with IC(50) values of 71 microM.
      Salicylsalicylic acid is not as potent as the original inhibitors such as
      clavulanic acid, but it may be developed to be potent beta-lactamase inhibitor by
      chemical modification.

PMID- 19747809
TI  - Icariin isolated from Epimedium pubescens regulates osteoblasts anabolism through
      BMP-2, SMAD4, and Cbfa1 expression.
AB  - Epimedii herba is one of the most frequently used herbs in formulas prescribed
      for the treatment of osteoporosis in China. The main active flavonoid glucoside
      extracted from Epimedium pubescens is Icariin, which has been reported to enhance
      bone healing and reduce osteoporosis occurrence. However, the detailed molecular
      mechanisms remain unclear. In this present study, we examine the molecular
      mechanisms of icariin by using primary osteoblast cell cultures obtained from
      adult mice. The osteoblast cells were harvested from 8-month old female
      Imprinting Control Region (ICR) mice. The effects of icariin stimulation on the
      proliferation, differentiation and maturation of osteoblasts were examined. The
      production of nitric oxide (NO) and caspase-3 were analyzed, along with the gene
      expressions of bone morphogenetic protein-2 (BMP-2), SMAD4, Cbfa1/Runx2, OPG, and
      RANKL. The viability of the osteoblasts reached its maximum at 10(-8)M icariin.
      At this concentration, icariin increased the proliferation and matrix
      mineralization of osteoblasts and promoted NO synthesis. With icariin treatment,
      the BMP-2, SMAD4, Cbfa1/Runx2, and OPG gene expressions were up-regulated; the
      RANKL gene expression was however down-regulated. Concurrent treatment involving
      the BMP antagonist (Noggin) or the NOS inhibitor (L-NAME) diminished the icariin
      induced cell proliferation, ALP activity, NO production, as well as the BMP-2,
      SMAD4, Cbfa1/Runx2, OPG, RANKL gene expressions. In this study, we demonstrate
      that in vitro icariin is a bone anabolic agent that may exert its osteogenic
      effects through the induction of BMP-2 and NO synthesis, subsequently regulating
      Cbfa1/Runx2, OPG, and RANKL gene expressions. This effect may contribute to its
      action on the induction of osteoblasts proliferation and differentiation,
      resulting in bone formation.

PMID- 19747810
TI  - Innate receptors and microbes in induction of autoimmunity.
AB  - Cells of the adaptive immune system (T and B cells) causing autoimmunity require
      activation signals that are normally provided by the innate immune system. Innate
      signaling receptors are obvious candidates for participation in the induction of
      autoimmunity, and the nature of these receptors suggests that microbes could be
      the triggers. Recent publications describing the development of autoimmunity in
      sterile conditions and in animals deficient in innate signaling question the
      requirement of these receptors for initiation of autoimmunity. In addition, the
      role of the non-pathogenic (commensal) microbiota as a regulator of autoimmunity
      has come into the spotlight. In this review we discuss recent reports that deal
      with the link between innate signaling receptors and 'adaptive' autoimmunity.

PMID- 19747811
TI  - Social and structural determinants of HAART access and adherence among injection
      drug users.
AB  - Highly active antiretroviral therapy (HAART) has dramatically improved health
      outcomes among people living with HIV/AIDS. However, significant rates of HIV
      related morbidity and mortality have persisted among HIV-positive injection drug
      users (IDU) globally. To date, research as well as programmatic and policy
      responses have failed to adequately address barriers to HAART access and
      adherence among IDU both in developing/transitional and developed countries. A
      review of existing literature suggests that this is due to a shortage of context
      specific evidence and an overemphasis on individual-level and behavioural
      variables. We propose a conceptual shift away from understanding suboptimal HAART
      adherence as determined predominantly by individual factors modifiable through
      individually focused interventions, towards a greater acknowledgement of the
      influence of social and structural factors such as stigmatization and social
      exclusion, unstable housing environments, the organization of health care systems
      and the continued prohibitionist approach to illicit drug policy. Globally, the
      future of a successful HAART treatment approach for HIV-positive IDU relies
      largely on a more careful consideration of these social and structural barriers
      that IDU face and, importantly, on a serious commitment to effect social and
      structural changes that will foster conditions which allow IDU to enjoy the full
      benefits of HAART.

PMID- 19747812
TI  - How to find non-dependent opiate users: a comparison of sampling methods in a
      field study of opium and heroin users.
AB  - BACKGROUND/AIM: The first aim is to better understand the potentials and
      limitations of different sampling methods for reaching a specific, rarely studied
      population of drug users and for persuading them to take part in a
      multidisciplinary study. The second is to determine the extent to which these
      different methods reach similar or dissimilar segments of the non-dependent
      opiate-using population. METHOD: Using ethnographic fieldwork (EFW) and targeted
      canvassing (TARC; small newspaper advertisements and website announcements),
      supplemented by snowball referrals, we recruited and interviewed 127 non
      dependent opiate users (lifetime prevalence of use 5-100 times; 86.6% had used
      heroin and 56.7% opium). Average age was 39.0; 66.1% were male and 33.9% female.
      RESULTS: In addition to opiates, many respondents had wide experience with other
      illicit drugs. The majority had non-conventional lifestyles. Both EFW and TARC
      yielded only limited numbers of snowball referrals. EFW requires specific skills,
      is labour-intensive, thus expensive, but allows unsuitable candidates to be
      excluded faster. Respondents recruited through EFW were significantly more likely
      to have experience with opium and various drugs other than opiates. TARC resulted
      in larger percentages of women and respondents with conventional lifestyles. TARC
      is less labour-intensive but requires more time for screening candidates; its
      cost-effectiveness depends on the price of advertising for the recruitment.
      CONCLUSION: Different methods reach different segments of the population of non
      dependent opiate users. It is useful to employ a multi-method approach to reduce
      selectivity.

PMID- 19747813
TI  - Effects of temperature on the release of nutrient elements of solid organic
      materials under conditions of oversaturation.
AB  - The effects of temperature on the release of chemical components of six solid
      organic materials under conditions of oversaturation were investigated in this
      paper. The six materials were peat moss (PM), weathered coals (WC), charred rice
      husks (CRH), sawdust (Sd), turfgrass clippings (TC), and chicken manure (CM).
      Significant differences were observed in the available nitrogen and phosphorus
      content of the aqueous extracts of organic materials at different temperatures.
      The available nitrogen content in aqueous extracts of PM and WC at 25 degrees C
      was higher than that registered at 15 degrees C and 35 degrees C. Available
      nitrogen content in the aqueous extracts of CRH, Sd, TC, and WC at 35 degrees C
      was higher than at 15 degrees C and 25 degrees C. The available phosphorus
      content in the aqueous extracts of organic materials at 35 degrees C was higher
      than that available at 15 degrees C and 25 degrees C, with the exception of Sd.
      In addition, the release of available phosphorus in the aqueous solution of
      organic materials at different temperatures varied constantly for 108h. The
      release of potassium (K(+)) and sodium (Na(+)) ions in the aqueous extracts of
      organic materials was basically steady over time, with the exception of CM. High
      temperature (35 degrees C) may significantly hasten the release of K(+) from
      organic substrates (except for WC) with low temperatures significantly inhibiting
      release of K(+) in Sd and CRH. High temperatures (35 degrees C) might
      significantly facilitate the release of Na(+) in CM and TC. However, no
      significant differences were manifested in the release of Na(+) from organic
      substrates at different temperatures, with the exception of CM and TC. Moreover,
      no significant differences were observed in the release of calcium, magnesium and
      iron ions with time, nor were there any significant differences in the contents
      of iron ions in the aqueous extracts of organic materials at different
      temperatures. The results indicate that multiple mediums should be pretreated in
      water for a week before being used for planting. They should be used when all
      mineral elements of organic materials are steady and ignoring the effect of
      organic mediums.

PMID- 19747814
TI  - Concanavalin A and polyvinyl butyral use as a potential dengue electrochemical
      biosensor.
AB  - Immobilization of concanavalin A on gold electrode by means of gold nanoparticles
      and polyvinyl butyral was carried out and investigated by cyclic voltammetry and
      electrochemical impedance spectroscopy. The system was tested with sera from
      patients infected by dengue fever (DF) and dengue hemorrhagic fever (DHF).
      Electrochemical impedance spectroscopy (in the frequency range from 100mHz to
      100KHz), and cyclic voltammetry (from -0.2 to 0.7V vs. Ag/AgCl), was performed in
      phosphate buffer solution containing 10mM K(3)[Fe(CN)(6)]/K(4)[Fe(CN)(6)] (1:1)
      mixture as a redox probe. As biomolecules accumulated on the electrode surface
      the voltammetric response changed from a clear diffusional to an irreversible
      behavior. Impedance spectroscopy showed a clear increase of the electron-transfer
      resistance when the sensor is exposed to contaminated sera (DF or DHF) as
      compared to exposure to uncontaminated serum (NDF). The results were analyzed
      through an equivalent circuit and values of charge transfer resistance and
      capacitance were obtained. Variations in charge transfer resistance were used to
      distinguish the sensor response for the different sera investigated (DF, DHF and
      NDF). Alternatively, a three-dimensional graph gave the best response for
      differentiation of all three blood sera. The distinctive patterns of impedimetric
      responses observed were ascribed to different glycoprotein patterns in the sera
      investigated. Therefore, the lectin immobilization on electrode surface with gold
      nanoparticles and polyvinyl butyral, combined with the three-dimensional
      impedance analysis introduced herein are valuable tools in the development of a
      biosensor for immunological response to diseases.

PMID- 19747815
TI  - Layer-by-layer assembly of electro-active gold nanoparticle/cytochrome c
      multilayers.
AB  - In this study we have tested the use of modified gold nanoparticles (GNPs) for
      introduction into cytochrome c (CytC) multilayer assemblies, constructed by the
      layer-by-layer deposition technique. For this purpose gold nanoparticles of
      different size are synthesized and the GNPs modified with mercaptopropionic acid
      (MPA). The particles are characterized by UV-vis-spectroscopy and transmission
      electron microscopy (TEM). The modified particles have been studied with respect
      to their binding capability on a CytC layer by SPR. The negatively charged
      particles exhibit rather fast adsorption kinetics on CytC. We can also show that
      CytC binds to MPA-modified gold nanoparticles. For the construction of electro
      active CytC multilayers a negatively charged polyelectrolyte can be used. We
      demonstrated that the polyelectrolyte can be replaced by small-sized GNPs (5nm)
      in the multilayer assemblies, but assemblies consisting only of GNPs and CytC can
      be formed too. When these arrangements are prepared on gold electrodes, full
      electro-activity of the redox protein in the multiple layers can be obtained.
      CytC exhibits a formal potential of -24+/-12mV vs. Ag/AgCl. The electrochemical
      response is linearly increasing with the number of layers deposited, reaching a
      CytC surface concentration of 100pmol/cm(2) with 6 layers. The electron transfer
      mechanism through the layer system and the particle size influence are discussed.

PMID- 19747816
TI  - Sequence-specific detection of trace DNA via a junction-probe electrochemical
      sensor employed template-enhanced hybridization strategy.
AB  - A novel junction-probe electrochemical biosensor for the sequence-specific
      detection of DNA with higher sensitivity and higher discrimination ability was
      described in here. This DNA biosensor is based on "junction-probe" detection
      strategy, which operates via a concept called template-enhanced hybridization
      processes (TeHyP). TeHyP encompasses a design strategy whereby two probes that do
      not hybridize to each other at a specific temperature can be made to anneal to
      each other in the presence of a template (target) via the formation of a ternary
      complex ("Y" junction structure). The resulting structure that forms after the
      template-enhanced hybridization then was detected by electrochemical method with
      [Ru(NH(3))(6)](3+) as signal molecule. We demonstrated that the formation of "Y"
      junction structure brings more [Ru(NH(3))(6)](3+) to the electrode surface via
      electrostatic interaction and results in an increasing electrochemical signal.
      The increasing electrochemical signal sensitively reflects the concentration of
      target DNA and shows a good linear relationship with the concentration of target
      DNA. By employing above strategy, this DNA biosensor could detect as low as 7.6
      x10(-13)M target DNA and exhibited high discrimination ability even against
      single-base mismatch. In addition, this novel DNA biosensor is easy to fabricate
      and convenient to operate, and shows good stability, reproducibility and
      reusability.

PMID- 19747817
TI  - DNA aptamer-based QDs electrochemiluminescence biosensor for the detection of
      thrombin.
AB  - A novel biosensor for the detection of thrombin was developed by using QDs
      electrochemiluminescence (ECL) technique. The thiol-terminated aptamer with 15
      nucleotides (probe I) was first immobilized on Au electrode, and then thrombin
      was imported to form the aptamer-thrombin bioaffinity complexes. Another 5'
      biotin modified aptamer (29 nucleotides, probe II) was next hybridized with the
      combined thrombin to form a sandwich type structure. Streptavidin modified QDs
      (avidin-QDs) were bound to probe II via the biotin-avidin-system. The QDs ECL
      signal was responsive to the amount of probe II, which was indirect proportional
      to the combined thrombin. The ECL intensity of the biosensor increased with the
      increase of thrombin concentration in the range of 0-20 microgmL(-1). In
      addition, the biosensor exhibited the excellent selectivity responses and good
      stability toward the target analyte.

PMID- 19747818
TI  - Three-dimensionally ordered macroporous (3DOM) gold-nanoparticle-doped titanium
      dioxide (GTD) photonic crystals modified electrodes for hydrogen peroxide
      biosensor.
AB  - Gold nanoparticles have been introduced into the wall framework of titanium
      dioxide photonic crystals by the colloidal crystal template technique. The three
      dimensionally ordered macroporous gold-nanoparticle-doped titanium dioxide (3DOM
      GTD) film was modified on the indium-tin oxide (ITO) electrode surface and used
      for the hydrogen peroxide biosensor. The direct electron transfer and
      electrocatalysis of horseradish peroxidase (HRP) immobilized on this film have
      been investigated. The 3DOM GTD film could provide a good microenvironment for
      retaining the biological bioactivity, large internal area, and superior
      conductivity. The HRP/3DOM GTD/ITO electrode exhibited two couples of redox peaks
      corresponding to the HRP intercalated in the mesopores and adsorbed on the
      external surface of the film with the formal potential of -0.19 and -0.52V in
      0.1M PBS (pH 7.4), respectively. The HRP intercalated in the mesopores showed a
      surface-controlled process with a single proton transfer. The direct electron
      transfer between the adsorbed HRP and the electrode is achieved without the aid
      of an electron mediator. The H(2)O(2) biosensor displayed a rapid eletrocatalytic
      response (less than 3s), a wide linear range from 0.5 microM to 1.4mM with a
      detection limit of 0.2 microM, high sensitivity (179.9 microAmM(-1)), good
      stability and reproducibility. Compared with the free-Au doped titanium dioxide
      photonic crystals modified electrode, the GTD modified electrode could greatly
      enhance the response current signal, linear detection range and higher
      sensitivity. The 3DOM GTD provided a new matrix for protein immobilization and
      direct transfer study and opened a way for low conductivity electrode biosensor.

PMID- 19747819
TI  - Prediction and classification of the modes of genotoxic actions using bacterial
      biosensors specific for DNA damages.
AB  - We report on a novel approach to predict the mode of genotoxic action of
      chemicals using a series of DNA damage specific bioluminescent bacteria. For
      this, a group of seven different DNA damage sensing recombinant bioluminescent
      strains were employed. Each of these strains was tested against model DNA
      damaging agents, such as mitomycin C (MMC), 1-methyl-1-nitroso-N-methylguanidine
      (MNNG), nalidixic acid (Nal) and 4-nitroquinoline N-oxide (4-NQO). These
      biosensors were grouped based on their responses to a specific mode of genotoxic
      action, such as (a) DNA damage cascade response (biosensor with nrdA-, dinI- and
      sbmC-lux), (b) SOS response or DNA repair (strains carrying recA-, recN- and sulA
      lux), and (c) DNA damage potentially by alkylation (biosensor with alkA-lux). The
      differential response patterns and its strength of these strains to various model
      genotoxicants allowed classifying the chemical's potential genotoxic mode.
      Therefore, it is possible to elucidate and classify the mode of genotoxic impacts
      of an unknown sample and that together they may be utilized in the pre-screening
      steps of new drugs, newly synthesized chemicals, food and environmental
      contaminants.

PMID- 19747820
TI  - Acidolysis of a lignin model: investigation of heterogeneous catalysis using
      Montmorillonite clay.
AB  - The use of heterogeneous conditions involving Montmorillonite K10 clay was
      investigated as a mild alternative to homogeneous acidolysis of a lignin model.
      Guaiacyl Dehydrogenation Oligomers (DHOs) synthesized by horseradish peroxidase
      were selected as starting material. Hydrolysis products were analyzed by gel
      permeation chromatography and by HPLC/mass spectrometry. Several experimental
      parameters were studied such as catalyst and substrate concentration, as well as
      reaction solvent composition in order to minimize high molar mass product
      formation generated by recombination mechanisms. In both catalytic modes, the
      best hydrolysis conditions were similar in terms of solvent composition with
      dioxane/water (90/10, v/v) and catalyst H(+) concentration of about 0.01 mol/L.
      Although the homogeneous catalysis generated only 28% of low molecular weight
      (LMW) products (monomers and dimers), clay catalysis generated 35%. In light of
      the qualitative analysis, both catalytic methods gave the same products, thus
      supporting similar hydrolysis mechanisms.

PMID- 19747821
TI  - Thermophilic anaerobic co-digestion of cattle manure with agro-wastes and energy
      crops: comparison of pilot and full scale experiences.
AB  - The paper deals with the benefits coming from the application of a proper process
      temperature (55 degrees C) instead of a 'reduced' thermophilic range (47 degrees
      C), that is often applied in European anaerobic co-digestion plants. The
      experimental work has pointed out that biogas production improve from 0.45 to
      0.62 m(3)/kg VS operating at proper thermophilic conditions. Moreover, also
      methane content was higher: from 52% to 61%. A general improvement in digester
      behaviour was clear also considering the stability parameters comparison (pH,
      ammonia, VFA content). The second part of the study takes into account the
      economic aspects related to the capital cost of anaerobic digestion treatment
      with a 1 MW co-generation unit fro heat and power production (CHP). Moreover, the
      economic balance was also carried out considering the anaerobic supernatants
      treatment for nitrogen removal. The simulation showed how a pay-back-time of 2.5
      yr and between 3 and 5 yr respectively could be determined when the two options
      of anaerobic digestion only and together with the application of a nitrogen
      removal process were considered.

PMID- 19747822
TI  - Effect of cytostatic drug presence on extracellular polymeric substances
      formation in municipal wastewater treated by membrane bioreactor.
AB  - The effect of the cyclophosphamide and its mean metabolites on extracellular
      polymeric substances (EPS) formation was investigated. Two lab-scale membrane
      bioreactors were followed in parallel (one with the cytostatic drugs, the second
      without). Chromatographic and spectroscopic studies (UV-Vis spectroscopy and IR
      spectroscopy) showed that the presence of CPs induced an increase in EPS
      concentration in the biological sludge, especially of soluble substances, mainly
      polysaccharides and proteins. Size exclusion chromatography analysis revealed
      that in the presence of CPs, macromolecular EPS were formed (polysaccharides
      corresponding to about 6 KDa and proteins to about 18 KDa). The formation of EPS
      seemed to be a protection mechanism. More important membrane fouling in reactor
      with CPs seemed to be related to the retention of an increased amount of soluble
      substances.

PMID- 19747823
TI  - Synthetic substrate for application in both high and low throughput assays for
      botulinum neurotoxin B protease inhibitors.
AB  - A FRET peptide substrate was synthesized and evaluated for enzymatic cleavage by
      the BoNT/B light chain protease. The FRET substrate was found to be useful in
      both a high throughput assay to uncover initial 'hits' and a low throughput HPLC
      assay to determine kinetic parameters and modes of inhibition.

PMID- 19747824
TI  - Extension of Drosophila life span by RNAi of the mitochondrial respiratory chain.
AB  - BACKGROUND: Mitochondria have long been proposed to play an important role in the
      aging process. In the nematode Caenorhabditis elegans, genes important for
      mitochondrial electron transport chain (ETC) function stand out as a principal
      group of genes affecting life span. However, it has been suggested that this may
      be a peculiarity of nematode biology. In the present study, we have used an in
      vivo RNA interference (RNAi) strategy to inactivate ETC genes in Drosophila
      melanogaster and examine the impact on longevity. RESULTS: Here, we report that
      RNAi of five genes encoding components of mitochondrial respiratory complexes I,
      III, IV, and V leads to increased life span in flies. Long-lived flies with
      reduced expression of ETC genes do not consistently show reduced assembly of
      respiratory complexes or reduced ATP levels. In addition, extended longevity is
      not consistently correlated with reduced fertility or increased resistance to the
      free-radical generator paraquat. Targeted RNAi of two complex I genes in adult
      tissues or in neurons alone is sufficient to extend life span. CONCLUSIONS: Our
      data suggest that the role of mitochondrial ETC function in modulating animal
      aging is evolutionarily conserved and might also operate in humans. Furthermore,
      our findings suggest that the longer life span of flies with reduced ETC gene
      expression cannot simply be attributed to reduced energy production leading to
      decreased "rate of living."

PMID- 19747825
TI  - Rapidly shifting sex ratio across a species range.
AB  - Sex ratios are subject to distortion by a range of inherited parasites. Although
      it has been predicted that the presence of these elements will result in spatial
      and temporal variation in host sex ratio, testing of this hypothesis has been
      constrained by availability of historical data. We here determine spatial and
      temporal variation in sex ratio in a interaction between a butterfly and male
      killing Wolbachia bacteria by assaying infection presence in museum specimens,
      and from this inferring infection prevalence and phenotype in historical
      populations. Comparison of contemporary and museum samples revealed profound
      change in four of five populations examined. Two populations become extremely
      female biased, associated with spread of the male-killer bacterium. One evolved
      from extremely female biased to a sex ratio near parity, resulting from the
      infection losing male-killing activity. The final population fluctuated widely in
      sex ratio, associated with varying frequency of the male killer. We conclude that
      asynchronous invasion and decline of sex-ratio distorters combines with the
      evolution of host suppressors to produce a rapidly changing mosaic of sex ratio.
      As a consequence, the reproductive ecology of the host species is likely to be
      fundamentally altered over short time scales. Further, the study demonstrates the
      utility of museum specimens as "silent witnesses" of evolutionary change.

PMID- 19747826
TI  - Bacterial evolution by genomic island transfer occurs via DNA transformation in
      planta.
AB  - Our understanding of the evolution of microbial pathogens has been advanced by
      the discovery of "islands" of DNA that differ from core genomes and contain
      determinants of virulence. The acquisition of genomic islands (GIs) by horizontal
      gene transfer (HGT) is thought to have played a major role in microbial
      evolution. There are, however, few practical demonstrations of the acquisition of
      genes that control virulence, and, significantly, all have been achieved outside
      the animal or plant host. Loss of a GI from the bean pathogen Pseudomonas
      syringae pv. phaseolicola (Pph) is driven by exposure to the stress imposed by
      the plant's resistance response. Here, we show that the complete episomal island,
      which carries pathogenicity genes including the effector avrPphB, transfers
      between strains of Pph by transformation in planta and inserts at a specific att
      site in the genome of the recipient. Our results show that the evolution of
      bacterial pathogens by HGT may be achieved via transformation, the simplest
      mechanism of DNA exchange. This process is activated by exposure to plant
      defenses, when the pathogen is in greatest need of acquiring new genetic traits
      to alleviate the antimicrobial stress imposed by plant innate immunity.

PMID- 19747827
TI  - Notch signaling functions as a cell-fate switch between the endothelial and
      hematopoietic lineages.
AB  - Recent studies have begun to elucidate how the endothelial lineage is specified
      from the nascent mesoderm. However, the molecular mechanisms which regulate this
      process remain largely unknown. We hypothesized that Notch signaling might play
      an important role in specifying endothelial progenitors from the mesoderm, given
      that this pathway acts as a bipotential cell-fate switch on equipotent progenitor
      populations in other settings. We found that zebrafish embryos with decreased
      levels of Notch signaling exhibited a significant increase in the number of
      endothelial cells, whereas embryos with increased levels of Notch signaling
      displayed a reduced number of endothelial cells. Interestingly, there is a
      concomitant gain of endothelial cells and loss of erythrocytes in embryos with
      decreased Notch activity, without an effect on cell proliferation or apoptosis.
      Lineage-tracing analyses indicate that the ectopic endothelial cells in embryos
      with decreased Notch activity originate from mesodermal cells that normally
      produce erythrocyte progenitors. Taken together, our data suggest that Notch
      signaling negatively regulates the number of endothelial cells by limiting the
      number of endothelial progenitors within the mesoderm, probably functioning as a
      cell-fate switch between the endothelial and the hematopoietic lineages.

PMID- 19747828
TI  - Buildup of choice-predictive activity in human motor cortex during perceptual
      decision making.
AB  - Simple perceptual decisions are ideally suited for studying the sensorimotor
      transformations underlying flexible behavior. During perceptual detection, a
      noisy sensory signal is converted into a behavioral report of the presence or
      absence of a perceptual experience. Here, we used magnetoencephalography (MEG) to
      link the dynamics of neural population activity in human motor cortex to
      perceptual choices in a "yes/no" visual motion detection task. We found that (1)
      motor response-selective MEG activity in the "gamma" (64-100 Hz) and "beta" (12
      36 Hz) frequency ranges predicted subjects' choices several seconds before their
      overt manual response; (2) this choice-predictive activity built up gradually
      during stimulus viewing toward both "yes" and "no" choices; and (3) the choice
      predictive activity in motor cortex reflected the temporal integral of gamma-band
      activity in motion-sensitive area MT during stimulus viewing. Because gamma-band
      activity in MT reflects visual motion strength, these findings suggest that,
      during motion detection, motor plans for both "yes" and "no" choices result from
      continuously accumulating sensory evidence. We conclude that frequency-specific
      neural population activity at the cortical output stage of sensorimotor pathways
      provides a window into the mechanisms underlying perceptual decisions.

PMID- 19747829
TI  - Wnt11/5a complex formation caused by tyrosine sulfation increases canonical
      signaling activity.
AB  - Wnt signaling plays important roles in embryonic development, tissue
      differentiation, and cancer. In both normal and malignant tissue, Wnt family
      members are often expressed combinatorially, although the significance of this is
      not understood. We recently showed that Wnt11 and Wnt5a are both required for the
      initiation of embryonic axis formation and that the two proteins physically
      interact with each other. However, little is known about the mechanism or
      biological significance of Wnt-Wnt protein interaction. Here we show in three
      assays, with Xenopus oocytes, mouse L cells, and human embryonic stem cells, that
      secreted Xenopus Wnt11/5a complexes have more canonical Wnt signaling activity
      than secreted Wnt11 or Wnt5a acting alone. We demonstrate that the sulfation
      activity of tyrosylprotein sulfotransferase-1 (TPST-1) is required for Xenopus
      dorsal axis formation and that O-sulfation of specific tyrosine residues is
      necessary for the interaction of Wnt11 with Wnt5a and for enhanced canonical
      signaling activity. These findings demonstrate a novel aspect of Wnt biology-Wnt
      family member interaction that depends on tyrosyl sulfation.

PMID- 19747830
TI  - Assessment of kinematic and kinetic patterns following limb salvage procedures
      for bone sarcoma.
AB  - Bone sarcomas are the fourth most common cancer in individuals under 25 years.
      Limb salvage procedures have become increasingly popular for the treatment of
      osteosarcomas as they have functional and psychological benefits over traditional
      amputative procedures. The purpose of this paper was to evaluate kinematic and
      kinetic characteristics of patient's post-limb salvage and examine key predictive
      factors of gait dysfunction. A retrospective outcome study was undertaken on 20
      limb salvage patients (10 females, 10 males) recruited from the Queensland Bone
      Tumour Registry. Kinematic and kinetic data were collected using a 3D motional
      analysis system and three force platforms. Loading response knee flexion in the
      affected lower limb was reduced compared to the unaffected lower limb (P<0.001)
      and the control group (P<0.001), although, closer examination of results showed
      two contrasting patterns of knee flexion during loading. Multiple regression
      analysis showed that muscular integrity (i.e. strength, ROM and residual mass)
      was the most predictive factor of function following limb salvage surgery. ANOVA
      showed that patients treated with the Stanmore SIMLES prostheses exhibited
      superior torque and power production at the ankle during late stance compared to
      those treated with the Stryker HMRS. In summary, the results showed that limb
      salvage patients adopted a gait pattern that reduced the moment demand at the
      knee and hip, suggesting a compensation for pain, reduced stability and/or muscle
      weakness.

PMID- 19747831
TI  - Comparative molecular field analysis and synthetic validation of a hydroxyamide
      propofol binding and functional block of neuronal voltage-dependent sodium
      channels.
AB  - Voltage gated sodium channels represent an important therapeutic target for a
      number of neurological disorders including epilepsy. Unfortunately, medicinal
      chemistry strategies for discovering new classes of antagonist for trans-membrane
      ion channels have been limited to mostly broad screening compound arrays. We have
      developed new sodium channel antagonist based on a propofol scaffold using the
      ligand based strategy of comparative molecular field analysis (CoMFA). The
      resulting CoMFA model was correlated and validated to provide insights into the
      design of new antagonists and to prioritize synthesis of these new structural
      analogs (compounds 4 and 5) that satisfied the steric and electrostatic model.
      Compounds 4 and 5 were evaluated for [(3)H]-batrachotoxinin-A-20-alpha-benzoate
      ([(3)H]-BTX-B) displacement yielding IC(50)'s of 22 and 5.7 microM, respectively.
      We further examined the potency of these two compounds to inhibit neuronal sodium
      currents recorded from cultured hippocampal neurons. At a concentration of 50
      microM, compounds 4 and 5 tonically inhibited sodium channels currents by 59+/
      7.8% (n=5) and 70+/-7.5% (n=7), respectively. This clearly demonstrates that
      these compounds functionally antagonize native neuronal sodium channel currents.
      In summary, we have shown that CoMFA can be effectively used to discover new
      classes of sodium channel antagonists.

PMID- 19747832
TI  - Design, synthesis and biological evaluation of tripeptide boronic acid proteasome
      inhibitors.
AB  - A series of tripeptide boronate proteasome inhibitors were designed and
      synthesized on the basis of our previously built tripeptide aldehyde 3D-QSAR
      models. All the synthesized compounds were evaluated for their proteasome
      inhibitory activities in an isolated 20S rabbit proteasome, and selected
      compounds were evaluated for their antitumor activities in vitro against four
      human cancer cell lines. Biological results showed bulky and negative
      substituents at P(2) position improved the proteasome-inhibitory potency
      obviously, which completely conformed to the theoretical models, while those at
      P(3) position thoroughly deviated from the 3D-QSAR model. Most of the screened
      compounds showed less than 1 nM inhibitory potency and high selectivity against
      20S proteasome, of which 7f is the most potent (IC(50)=0.079 nM) and twofold more
      active than bortezomib (IC(50)=0.161 nM). Cell viability indicated hydrophilic 4
      hydroxyphenyl substituent at P(2) or P(3) position was not favorable to the
      cellular activities. Especially for the two hematologic cancer cell lines, HL-60
      and U266, 7f inhibited them at the level of less than 10 nM and was more potent
      than the control bortezomib. It is being considered a promising new lead to be
      developed for the treatment of various cancers.

PMID- 19747833
TI  - Novel 7H-pyrrolo[2,3-d]pyrimidine derivatives as potent and orally active STAT6
      inhibitors.
AB  - Signal transducers and activators of transcription 6 (STAT6) is an important
      transcription factor in interleukin (IL)-4 signaling pathway and a key regulator
      of the type 2 helper T (Th2) cell immune response. Therefore, STAT6 may be an
      excellent therapeutic target for allergic conditions, including asthma and atopic
      diseases. Previously, we reported 4-aminopyrimidine-5-carboxamide derivatives as
      STAT6 inhibitors. To search for novel STAT6 inhibitors, we synthesized fused
      bicyclic pyrimidine derivatives and identified a 7H-pyrrolo[2,3-d]pyrimidine
      derivative as a STAT6 inhibitor. Optimization of the pyrrolopyrimidine
      derivatives led to identification of 2-[4-(4-{[7-(3,5-difluorobenzyl)-7H
      pyrrolo[2,3-d]pyrimidin-2-yl]amino}phenyl)piperazin-1-yl]acetamide (24,
      AS1810722) which showed potent STAT6 inhibition and a good CYP3A4 inhibition
      profile. Compound 24 also inhibited in vitro Th2 differentiation without
      affecting type 1 helper T (Th1) cell differentiation and eosinophil infiltration
      in an antigen-induced mouse asthmatic model after oral administration.

PMID- 19747834
TI  - Thienylhalomethylketones: Irreversible glycogen synthase kinase 3 inhibitors as
      useful pharmacological tools.
AB  - Thienylhalomethylketones, whose chemical, biological, and pharmaceutical data are
      here reported, are the first irreversible inhibitors of GSK-3beta described to
      date. Their inhibitory activity is likely related to the cysteine residue present
      in the ATP-binding site, which is proposed as a relevant residue for modulation
      of GSK-3 activity. The good cell permeability of the compounds allows them to be
      used in different cell models. Overall, the results presented here support the
      potential use of halomethylketones as pharmacological tools for the study of GSK
      3beta functions and suggest a new mechanism for GSK-3beta inhibition that may be
      considered for further drug design.

PMID- 19747835
TI  - Mechanisms of karyotype differentiation in Cassidinae sensu lato (Coleoptera,
      Polyphaga, Chrysomelidae) based on seven species of the Brazilian fauna and an
      overview of the cytogenetic data.
AB  - Among the subfamilies of Chrysomelidae, Cassidinae sensu lato (s.l.) includes
      6000 species distributed in 43 tribes. Approximately 100 of these species were
      cytogenetically analyzed and most of them presented 2n=18=16+Xy(p), which was
      smaller than 2n=20=18+Xy(p) considered basal for Polyphaga. However, some groups
      of species presented maintenance of the basal diploid number and others showed
      increase in this number. Certain species of the latter group also exhibited
      variation in the type of sex chromosome system (SCS). Considering the recent
      taxonomic revision accomplished for the Cassidinae s.l. species, the existence of
      phylogenetic relationship for some species of this subfamily, the high diversity
      of species of this group in the Neotropical region, and the low number of
      Cassidinae s.l. species karyotyped so far, the aim of the present work was to
      establish the main mechanisms involved in the karyotype evolution of this
      subfamily through the study of seven species of the Brazilian fauna and overview
      of the cytogenetic data. The individuals were collected in southeast and south of
      Brazil. The chromosomal preparations obtained from embryo and testes of adult
      males were stained with Giemsa solution. The species Agroiconota inedita
      (2n=42=40+Xy(p)), Charidotella (s.str.) immaculata (2n=22=20+Xy(p)), Charidotella
      (s.str.) sexpunctata (2n=22=20+Xy(p)), and Stolas chalybaea (2n=24=22+Xy(p))
      revealed diploid number higher than that established as basal for Polyphaga and
      biarmed chromosomes. The karyotype of Cteisella confusa, Deloyala cruciata, and
      Metriona elatior showed the chromosomal formulae 2n=18=16+Xy(p) considered modal
      for Cassidinae s.l. and biarmed chromosomes. The seven species exhibited easily
      identified sex chromosomes due to their size and/or morphology. The analysis of
      meiotic cells of all the species showed pachytenes with a positively
      heteropycnotic block probably corresponding to the sex chromosomes; diplotenes
      with a high number of bivalents with two chiasmata and sex chromosomes in a
      parachute configuration, and metaphases II that confirmed the chromosomal
      morphology, the type of SCS, and the regular segregation of all chromosomes. The
      data regarding to the number and morphology of the chromosomes, their behaviour
      during meiosis, and type of SCS were inedit for the majority of these species. In
      relation to the all Cassidinae s.l. species that presented SCS of the Xy(p) type,
      A. inedita was that with the highest diploid number. Furthermore, this work
      reported for the first time the cytogenetic information of representatives of the
      genera Cteisella and Metriona. Taking into account the phylogenetic and
      cytogenetic data of Cassidinae s.l. species, the karyotype differentiation of
      this group seems to have occurred from the basal karyotype of Polyphaga by
      decrease in the chromosome number and subsequent increase in this number.
      Pericentric inversion, centric fusion and fission seem to have been the main
      mechanisms that promoted the evolution of the autosomes. However, in the sex
      chromosome evolution, the mechanisms involved were centric fission and/or
      chromosomal translocation.

PMID- 19747836
TI  - Proventriculus of Cephalotes ants: a structural and comparative analysis.
AB  - The use of optic microscopy and scanning electron microscopy propitiated the
      comparative examination of the structure of the proventriculus bulb of Cephalotes
      atratus, Cephalotes clypeatus and Cephalotes pusillus. This portion of the
      digestive tract possesses highly sclerotized projections which act in the
      selection of victuals. This structure is of importance to phylogeny studies and
      thus was compared with others known species of ants in a dendrogram adapted from
      Eisner (1957). We did not detect differences among the three studied species in
      the nature of histochemistry and ultra morphology.

PMID- 19747837
TI  - Does video-assisted thoracoscopic lobectomy for lung cancer provide improved
      functional outcomes compared with open lobectomy?
AB  - OBJECTIVE: We evaluated video-assisted thoracic surgery (VATS) and open (OPEN)
      lobectomy for lung cancer and impact upon 6-month postoperative (postop)
      functional health status and quality of life. METHODS: In this retrospective
      analysis of prospective, observational data, anatomic lobectomy with staging
      thoracic lymphadenectomy was performed with curative intent for lung cancer. OPEN
      consisted of either thoracotomy (TH) or median sternotomy (MS). Technique was
      selected on the basis of anatomic imperative (OPEN: larger or central; VATS
      smaller or peripheral tumours) and/or surgical skills (VATS lobectomy initiated
      in 2001). All patients completed the Short Form 36 Health Survey (SF36) and
      Ferrans and Powers quality-of-life index (QLI) preoperatively (preop) and 6
      months postop. RESULTS: A total of 241 patients underwent lobectomy (OPEN, 192;
      VATS, 49). OPEN included MS 128 and TH 64. Comparison of MS and TH patient
      demographics, co-morbidities, pulmonary variables, intra-operative variables,
      stage and cell type, postop complications and 6-month clinical outcomes found no
      differences, allowing grouping together into OPEN. The VATS group had better
      pulmonary function testing (PFT), more adenocarcinoma and lower stage. The VATS
      and OPEN groups did not differ regarding operating time, postop complications and
      operative or 6-month mortality. The VATS group had less blood loss, transfusion,
      intra-operative fluid administration and shorter length of stay. Comparing within
      each group's preop to 6-month postop data, VATS patients were either the same or
      better in all SF36 categories (physical functioning, role functioning - physical,
      role functioning - emotional, social functioning, bodily pain, mental health,
      energy and general health). The OPEN group, however, was significantly worse in
      SF36 categories physical functioning, role functioning - physical and social
      functioning. The preop and 6 months postop VATS versus OPEN QLI scores were not
      different. At 6 months postop, hospital re-admission and use of pain medication
      was less in the VATS group. In addition, the VATS group had better preservation
      of preop performance status. CONCLUSIONS: VATS lobectomy for curative lung cancer
      resection appears to provide a superior functional health recovery compared with
      OPEN techniques.

PMID- 19747838
TI  - Rotation thromboelastometry (ROTEM) stability and reproducibility over time.
AB  - BACKGROUND: Thromboelastometry is a whole blood assay performed to evaluate the
      viscoelastic properties during blood clot formation and lysis. Rotation
      thromboelastography (ROTEM), Pentapharm GmbH, Munich, Germany) has overcome some
      of the limitations of classic thromboelastography. So far, no clinical validation
      on reproducibility (inter- and intra-assay variability) and sample stability over
      time has been published. METHODS: To evaluate the pre-analytic aspects, sample
      stability over time was assessed in 48 patients in eight age groups. Citrated
      blood was stored at room temperature. Tests measured every 30 min from T 0 min up
      to T 120 min on two ROTEM devices were INTEM (ellagic acid activated intrinsic
      pathway), EXTEM (tissue factor-triggered extrinsic pathway) and FIBTEM (with
      platelet inhibitor (cytochalasin D) evaluating the contribution of fibrinogen to
      clot formation). Precision by intra- and inter-assay variability was evaluated at
      two points of time in 10 volunteers. Finally, reference intervals and effect of
      age and sex were evaluated. RESULTS: Blood was stable over 120 min and no
      significant differences in ROTEM results were found. Maximum clot firmness
      measurements had a coefficient of variation of <3% for EXTEM, <5% for INTEM and
      <6% for FIBTEM. For clot formation time, the coefficient of variation was <4% for
      EXTEM and <3% for INTEM. Coefficient of variation for angle alpha was <3% for
      EXTEM and <6% for INTEM. The coefficient of variation for clotting time was <15%
      for both EXTEM and INTEM. Small but significant differences between ROTEM devices
      were found for maximum clot firmness in FIBTEM and INTEM as well as clot
      formation time and alpha angle in INTEM. CONCLUSIONS: ROTEM yields stable results
      over 120 min with a minimal variability on the same ROTEM device. However, small
      but significant differences between ROTEM devices were observed. Analysis should
      be performed on the same ROTEM device if small differences are of importance for
      treatment.

PMID- 19747839
TI  - An ex vivo methodology to assess the lipid peroxidation in stratum corneum.
AB  - Environmental risks, particularly UV radiation, provide a challenge to the
      function of the skin barrier. Protective measures such as the use of antioxidant
      products represent a possible method of providing protection to the skin. This
      paper reports the development of a non-invasive ex vivo method using tape strips
      of the outermost layers of stratum corneum (SC) from human volunteers in order to
      determine the effectiveness of an antioxidant emulsion topically applied to
      prevent lipid peroxidation (LPO) in the horny layer after an UV irradiation
      exposure. Two different formulations were used: formulation (A), containing
      Vitamin A, E and C, and formulation (B) containing fish extract. Both
      formulations were topically applied in vivo on volunteer forearms; then, a tape
      stripping of the SC of each volunteer was carried out. The lipid peroxidation was
      measured ex vivo after an UV irradiation of the SC samples. The amount of SC
      stripped to evaluate differences in lipid peroxidation, the UV irradiation
      intensity to form lipid peroxides and the accuracy of lipid peroxide analysis
      were optimized in this methodology using formulation (A). After an exposure
      application of seven days, a group of three strips of the outermost layers of SC
      of volunteers was irradiated with an intensity of 182.7 J/cm(2) to quantify the
      LPO inhibition. The percentage of LPO inhibition obtained after topical
      application of both formulations was in the range of 40-58% demonstrating the
      effectiveness of the formulations topically applied against lipid peroxidation on
      human SC. This methodology may be used as a quality control tool to determine ex
      vivo the percentage of the LPO inhibition on human SC for a variety of
      antioxidants topically applied.

PMID- 19747840
TI  - Studies on curcumin and curcuminoids. XXXIV. Photophysical properties of a
      symmetrical, non-substituted curcumin analogue.
AB  - Curcumin is the main constituent of curry. In its ground state it shows chemo
      preventive, chemo-therapeutic, anti-inflammatory and immune stimulating effects,
      and it is considered as a drug or drug model in the treatment of AIDS and cystic
      fibrosis. Further biological activity is induced in curcumin by light exposure:
      cytotoxicity is enhanced and photosensitized antibacterial effects are achieved.
      For the curcumin cis enol conformer, the fastest deactivation mechanism of the
      first excited singlet state is an excited-state intra-molecular proton transfer,
      which brings curcumin back to the ground state. This mechanism, as well as
      reketonization, interaction with the solvent and photodegradation, compete with
      the phototherapeutic action. The native compound curcumin carries phenolic
      hydroxyl and methoxy groups that influence the molecular charge distribution and
      hence the excited-state intra-molecular proton transfer rate in an unpredictable
      way. In this work we study static and time-resolved spectroscopic properties of a
      non-substituted curcuminoid that lacks both the phenolic hydroxyl and the
      phenolic methoxy groups. The photophysical properties of this compound are
      compared to those of native curcumin, in order to provide a rationale to the
      design of curcuminoids with molecular structures optimized for a photosensitizer.

PMID- 19747841
TI  - Depression as a risk factor for osteoporosis.
AB  - Osteoporosis is a major public health threat. Multiple studies have reported an
      association between depression and low bone mineral density, but a causal link
      between these two conditions is disputed. Here we review the endocrine and immune
      alterations secondary to depression that might affect bone mass. We also discuss
      the possible role of poor lifestyle in the etiology of osteoporosis in subjects
      with depression and the potential effect of antidepressants on bone loss. We
      propose that depression induces bone loss and osteoporotic fractures, primarily
      via specific immune and endocrine mechanisms, while poor lifestyle habits and use
      of specific antidepressants are potential contributory factors.

PMID- 19747842
TI  - A mechanistic study of the H/D exchange reactions of protonated arginine and
      arginine-containing di- and tripeptides.
AB  - The gas-phase H/D exchange reactions of arginine (R) and arginine-containing di-
      and tri-peptide (gly-arg (GR), arg-gly (RG), gly-gly-arg (GGR), gly-arg-gly (GRG)
      and arg-gly-gly (RGG)) [M + H]+ ions with deuterated ammonia (ND3) were
      investigated by using Fourier-transform ion cyclotron resonance mass spectrometry
      (FT-ICR), ion mobility-mass spectrometry (IM-MS), ab initio and density
      functional theory-based molecular orbital calculations and molecular modeling.
      Three exchanges are observed for arginine and arginine-containing tri-peptide [M
      + H]+ ions, whereas the di-peptide [M + H]+ ions undergo a single H/D exchange.
      In addition, C-terminal methylation blocks H/D exchange of arginine and the
      arginine-containing peptide [M + H]+ ions, and a single H/D exchange is observed
      for N-terminal acetylated arginine [M + H]+ ions. A general mechanism for H/D
      exchange involving a collision complex that is best described as a "solvated salt
      bridge" structure is proposed.

PMID- 19747843
TI  - A corona discharge initiated electrochemical electrospray ionization technique.
AB  - We report here the development of a corona discharge (CD) initiated
      electrochemical (EC) electrospray ionization (ESI) technique using a standard
      electrospray ion source. This is a new ionization technique distinct from ESI,
      electrochemistry inherent to ESI, APCI, and techniques using hydroxyl radicals
      produced under atmospheric pressure conditions. By maximizing the observable CD
      at the tip of a stainless steel ESI capillary, efficient electrochemical
      oxidation of electrochemically active compounds is observed. For electrochemical
      oxidation to be observed, the ionization potential of the analyte must be lower
      than Fe. Ferrocene labeled compounds were chosen as the electrochemically active
      moiety. The electrochemical cell in the ESI source was robust, and generated ions
      with selectivity according to the ionization potential of the analytes and up to
      zeptomolar sensitivity. Our results indicate that CD initiated electrochemical
      ionization has the potential to become a powerful technique to increase the
      dynamic range, sensitivity, and selectivity of ESI experiments.

PMID- 19747844
TI  - A robust two-dimensional separation for top-down tandem mass spectrometry of the
      low-mass proteome.
AB  - For fractionation of intact proteins by molecular weight (MW), a sharply improved
      two-dimensional (2D) separation is presented to drive reproducible and robust
      fractionation before top-down mass spectrometry of complex mixtures. The
      "GELFrEE" (i.e., gel-eluted liquid fraction entrapment electrophoresis) approach
      is implemented by use of Tris-glycine and Tris-tricine gel systems applied to
      human cytosolic and nuclear extracts from HeLa S3 cells, to achieve a MW-based
      fractionation of proteins from 5 to >100 kDa in 1 h. For top-down tandem mass
      spectroscopy (MS/MS) of the low-mass proteome (5-25 kDa), between 5 and 8 gel
      elution (GE) fractions are sampled by nanocapillary-LC-MS/MS with 12 or 14.5
      tesla Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometers.
      Single injections give about 40 detectable proteins, about half of which yield
      automated ProSight identifications. Reproducibility metrics of the system are
      presented, along with comparative analysis of protein targets in mitotic versus
      asynchronous cells. We forward this basic 2D approach to facilitate wider
      implementation of top-down mass spectrometry and a variety of other protein
      separation and/or characterization approaches.

PMID- 19747845
TI  - Mass spectrometric determination of ILPR G-quadruplex binding sites in insulin
      and IGF-2.
AB  - The insulin-linked polymorphic region (ILPR) of the human insulin gene promoter
      region forms G-quadruplex structures in vitro. Previous studies show that insulin
      and insulin-like growth factor-2 (IGF-2) exhibit high affinity binding in vitro
      to 2-repeat sequences of ILPR variants a and h, but negligible binding to variant
      i. Two-repeat sequences of variants a and h form intramolecular G-quadruplex
      structures that are not evidenced for variant i. Here we report on the use of
      protein digestion combined with affinity capture and MALDI-MS detection to
      pinpoint ILPR binding sites in insulin and IGF-2. Peptides captured by ILPR
      variants a and h were sequenced by MALDI-MS/MS, LC-MS and in silico digestion. On
      bead digestion of insulin-ILPR variant a complexes supported the conclusions. The
      results indicate that the sequence VCG(N)RGF is generally present in the captured
      peptides and is likely involved in the affinity binding interactions of the
      proteins with the ILPR G-quadruplexes. The significance of arginine in the
      interactions was studied by comparing the affinities of synthesized peptides
      VCGERGF and VCGEAGF with ILPR variant a. Peptides from other regions of the
      proteins that are connected through disulfide linkages were also detected in some
      capture experiments. Identification of binding sites could facilitate design of
      DNA binding ligands for capture and detection of insulin and IGF-2. The
      interactions may have biological significance as well.

PMID- 19747846
TI  - Double bond migration to methylidene positions during electron ionization mass
      spectrometry of branched monounsaturated fatty acid derivatives.
AB  - Electron ionization mass spectra of several monounsaturated methyl-branched fatty
      acid methyl and trimethylsilyl esters were examined. These spectra exhibited some
      intensive fragment ions, whose formation could be explained after double-bond
      migration to methylidene position. This preferential migration (substantiated by
      deuterium labeling) acts significantly in the case of monounsaturated fatty acid
      methyl and trimethylsilyl esters possessing a methyl branch localized between the
      penultimate and the C(4) positions (relative to the ester group), whatever the
      position of the double-bond. Allylic cleavage and gamma-hydrogen rearrangement of
      the ionized methylidene group thus formed afforded very interesting fragment
      ions, which could be particularly useful to determine branching positions of
      monounsaturated methyl-branched fatty acid methyl and trimethylsilyl esters
      without additional treatment.

PMID- 19747848
TI  - Seeking patterns in dream content: a systematic approach to word searches.
AB  - This paper systematizes the word search potential of DreamBank.net (Domhoff &
      Schneider, 2008a, 2008b) by formulating and testing a set of word strings that
      can be used as default analytic categories in future investigations. The word
      strings are applied to the 981 dream reports of college students gathered by Hall
      and Van de Castle (1966) and the 136 dream reports of an 80-year old male
      gathered by Bulkeley (2008a). The results show a basic compatibility with the
      frequencies identified by Hall and Van de Castle's labor-intensive method of
      content analysis employing teams of human coders. These findings support the
      expanded use of word search technologies for the scientific study of dream
      content and its relation to forms of waking consciousness.

PMID- 19747849
TI  - Chronic type 1 diabetes in spontaneously hypertensive rats leads to exacerbated
      cardiac fibrosis.
AB  - INTRODUCTION: Diabetes in human subjects is often associated with hypertension.
      The aim of this study was to examine the development of cardiac fibrosis
      following induction of type 1 diabetes in genetically hypertensive rats. METHODS:
      Diabetes was induced by streptozotocin (STZ) injection in 8-week-old normotensive
      Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs) for a duration
      of 16 or 24 weeks. Aged-matched, nondiabetic WKY and SHRs were used as controls.
      At termination of treatment, the rats were anaesthetized, hearts arrested in
      diastole and perfusion fixed. A comprehensive examination of cardiac fibrosis
      throughout the right and left ventricles was undertaken in picrosirius red
      stained sections, using image analysis and by undertaking collagen type I and
      type III immunohistochemistry. RESULTS: Induction of diabetes in the SHRs led to
      a marked increase in the levels of interstitial fibrosis in the left ventricle
      plus septum (LV+S) at both 16 and 24 weeks duration (59% and 43% increase,
      respectively) and also in the right ventricle after 24 weeks duration of diabetes
      (35% increase compared to the nondiabetic SHR). Exacerbated perivascular fibrosis
      was also observed in the LV+S in the diabetic-hypertensive rats at the later time
      point. These effects of induction of diabetes were not observed in the
      normotensive strain. CONCLUSIONS/INTERPRETATION: Our findings clearly demonstrate
      elevations in cardiac fibrosis when type 1 diabetes is combined with
      hypertension. Our findings thus stress the importance of closely monitoring both
      blood pressure and glucose levels in type 1 diabetic patients in order to prevent
      myocardial collagen deposition.

PMID- 19747850
TI  - Inducibility of atrial fibrillation depends not on inflammation but on atrial
      structural remodeling in rat experimental autoimmune myocarditis.
AB  - INTRODUCTION: There is increasing evidence to support a link between inflammation
      and atrial fibrillation (AF). However, the role of inflammation on new-onset AF
      is still to be elucidated. METHODS: Rats underwent induction of experimental
      autoimmune myocarditis (EAM). Atrial structural change was evaluated by
      echocardiography and histological analysis. Electrophysiological data and the in
      vivo atrial response to burst atrial pacing were evaluated in the acute (2 weeks
      after EAM induction) and chronic phases (8 weeks after induction). In addition,
      atrial pacing after 2, 4, and 6 h after lipopolysaccharide (LPS) infusion, when
      the expression of gap junctions was modified, were challenged with young healthy
      rats. RESULTS: AF was induced in 11 of 15 chronic phase EAM rats but not in
      either acute phase EAM rats or LPS infusion rats (P<.01). Echocardiography showed
      dilatation of both atrium and ventricle and a decrease in the ejection fraction
      in the chronic phase. Histology revealed severe inflammatory lesions only in the
      acute phase. Interstitial atrial fibrosis as well as the area of atrial myocyte
      increased in the chronic phase but not in the acute phase. CONCLUSIONS: AF could
      be induced in the chronic phase of myocarditis rats, but not in the acute phase
      of myocarditis rats or in rats with LPS infusion. Acute inflammation per se did
      not increase the occurrence of AF induction. Atrial structural remodeling caused
      by inflammation and hemodynamic effects is necessary to induce AF.

PMID- 19747851
TI  - Apoptosis-regulated survival of primarily extravascular cells in proliferative
      active poststent neointima.
AB  - BACKGROUND: Increased proliferation, mitigated apoptosis, and recruitment of
      primarily extravascular cells to injured vessels are important processes during
      neointima formation. Therefore, the goal of this study was to assess the
      spatiotemporal balance between proliferation and apoptosis and the influence of
      apoptosis on the survival of primarily extravascular cells in in-stent neointima.
      METHODS: Minipigs underwent stent implantation to abdominal aortic segments. At
      Days 1, 7, 14, 30, 60, and 90 after injury, arterial cross sections were analyzed
      by TUNEL assay to detect apoptotic cells. For immunohistochemical detection of
      Ki67+/proliferating cell nuclear antigen (PCNA)+ proliferative, caspase3+
      apoptotic, S100+/fascin+ dendritic, GFAP+ neural crest-derived cells and CD14+
      monocytes/macrophages, the alkaline phosphatase-anti-alkaline phosphatase (APAAP)
      method was used. RESULTS: In the incipient cell-rich neointima, both frequency of
      proliferation and apoptosis was maximal (Ki67, 28.5+/-2.2%; PCNA, 25.4+/-3.8%;
      TUNEL, 8.6+/-0.4%; caspase3, 7.9+/-4.3%). With time, parallel to the decline in
      the neointima cellularity, signaling for proliferation and apoptosis decreased.
      Throughout the time course of neointima development, the apoptotic activity was
      detected in primarily extravascular cells. CONCLUSIONS: Imbalance between
      proliferation and apoptosis and recruitment of dendritic cells,
      monocytes/macrophages, and neural crest-derived cells to the injured vessels may
      partly explain the formation of the hypercellular in-stent neointima. Herein,
      apoptosis is an important factor that regulates survival of primarily
      extravascular neointimal cells.

PMID- 19747852
TI  - Pathology of late-onset anthracycline cardiomyopathy.
AB  - INTRODUCTION: Anthracyclines are known to have acute cardiotoxicity.
      Anthracycline-induced dilated cardiomyopathy may have late onset and present
      years after administration of the drug. Several studies have described the
      clinical findings in patients with late-onset cardiomyopathy, including
      electrocardiography, exercise testing, echocardiography, and histological
      findings in endomyocardial biopsies; however, there is little information on the
      pathological changes that are found in explanted or autopsy hearts. METHODS: We
      reviewed the medical records and microscopic slides of heart tissue from one
      patient who had an autopsy and from nine patients who had cardiac transplants
      between 2001 and 2008. Heart weights were compared to historic controls (heart
      weights normalized for the patient's heights). Hematoxylin and eosin (H&E)
      stained slides were semiquantitated for evidence of necrosis, myocytolysis,
      interstitial fibrosis, replacement fibrosis, and the presence of inflammation.
      RESULTS: The average heart weight ranged from 231 to 470 g (mean=317 +/- 65 g,
      median=303 g). Review of the histological sections revealed no evidence of
      significant necrosis or myocytolysis. Interstitial fibrosis was identified in all
      10 patients, with six patients showing multifocal fibrosis, three patients
      showing diffuse fibrosis, and only one patient showing focal fibrosis.
      Replacement fibrosis was identified in six patients, with two patients displaying
      multifocal and four patients displaying focal replacement fibrosis. CONCLUSION:
      Late-onset cardiomyopathy is a serious consequence of anthracycline therapy
      resulting in death or the need for cardiac transplantation in some patients.
      Unlike most other forms of dilated cardiomyopathy, the major pathological changes
      appear to be interstitial and/or replacement fibrosis without significant cardiac
      hypertrophy.

PMID- 19747853
TI  - Molecular mechanisms of congenital heart disease.
AB  - BACKGROUND: Congenital heart disease (CHD) is the most common type of birth
      defect. Despite the many advances in our understanding of cardiac development and
      many genes related to cardiac development identified, the fundamental etiology
      for the majority of cases of congenital heart disease remains unknown. METHODS:
      This review summarizes normal cardiac development, outlines the recent
      discoveries of the genetic causes of CHD, and provides possible strategies for
      exploring them. RESULTS: CHD is a multifactorial complex disease, with
      environmental and genetic factors playing important roles. A number of causative
      genes of selected congenital heart defects and genetic syndromes have been found.
      The molecular mechanisms of CHD may include mutations in components of the
      cardiac gene network, altered haemodynamics, regulatory pathway of cardiac genes,
      micro-RNA dysfunction, epigenetics, adult congenital heart diseases, and so on.
      CONCLUSIONS: The molecular basis of CHD is an exciting and rapidly evolving
      field. The continuing advances in the understanding of the molecular mechanisms
      of CHD will hopefully result in improved genetic counseling and care of affected
      individuals and their families.

PMID- 19747854
TI  - Respiratory chain deficiency precedes the disrupted calcium homeostasis in
      chronic doxorubicin cardiomyopathy.
AB  - BACKGROUND: Doxorubicin causes a chronic cardiomyopathy in which genetic and
      functional lesions of mitochondria accumulate in the long-term. A disrupted Ca2+
      homeostasis is also implicated in doxorubicin cardiotoxicity. We investigated if
      the alterations in myocellular Ca2+ are primary or secondary to the respiratory
      chain dysfunction in chronic doxorubicin cardiomyopathy. METHODS AND RESULTS: A
      "long-observation group" of rats was treated with intravenous doxorubicin (1
      mg/kg per week) for 7 weeks, starting at 11 weeks of age. Controls received
      equivalents of saline. A "short-observation group" received seven injections of
      doxorubicin, starting at 41 weeks of age. All rats were euthanized at 48 weeks of
      age. Only the long-observation rats developed a significant clinical,
      macroscopic, histological, and ultrastructural cardiomyopathy. Their
      intramyocardial cytochrome c oxidase (COX) activity was lowest; they had the
      highest loss of mitochondrial DNA (mtDNA) and its encoded respiratory chain
      subunit COX I, and the highest amount of ultrastructural and intracellular
      calcium accumulation resembling hydroxyapatite. The short-term-group hearts had
      fewer alterations of the cardiomyopathy score, COX-activity, and mtDNA-content
      than the long-observation group. Despite a measurable loss of mtDNA and its
      encoded respiratory chain activity, however, there was virtually no detectable
      calcium accumulation in the hearts of the short-term group. CONCLUSIONS: mtDNA
      depletion and secondary respiratory chain dysfunction precedes the precipitation
      of mitochondrial calcium deposits in chronic doxorubicin cardiotoxicity.

PMID- 19747855
TI  - Detection of nanobacteria-like material from calcified cardiac valves with
      rheumatic heart disease.
AB  - BACKGROUND: Nanobacterium contributes to pathological calcification in human
      renal stones and psammoma bodies in ovarian cancer. Pathological calcification is
      also present in cardiac valves with rheumatic heart disease. The aim of this
      study was to detect, isolate, culture, and characterize nanobacteria-like
      material from human calcified cardiac valves with rheumatic heart disease.
      METHODS: Normal and calcified cardiac valve groups, as well as positive
      (nanobacteria strain Se90) and negative (serum radiated with 30 kGy of gamma-ray)
      control groups, were included in this study. Part of each valve was immunostained
      with nanobacterial antibody 8D10, and the remaining parts were homogenized,
      filtered, and maintained in culture. The cultures were checked with a microscope
      weekly. Culture medium at different time points was analyzed with a
      spectrophotometer. The cultures maintained for 3 weeks were further examined with
      immunofluorescence double staining and transmission electron microscopy. RESULTS:
      While 26 of 29 calcified valves stained positive for 8D10 antibody, all normal
      valves stained negative. Mobile tiny particles were observed under a microscope
      in the calcified valve group and the Se90 group. Optical densities were
      significantly different among groups (P<.001). Immunofluorescence double staining
      displayed tiny green fluorescence particles in the calcified valve group, in the
      Se90 group, and in two samples of the normal valve group. Transmission electron
      microscopy analysis indicated that cultured particles from calcified valves
      ranging in size from 88 to 341 nm had an obvious cell membrane structure similar
      to that of Se90. CONCLUSIONS: The nanobacteria-like material has been isolated
      and cultured from calcified cardiac valves with rheumatic heart disease, and its
      characteristics are similar to those of Se90.

PMID- 19747856
TI  - Ghrelin inhibits foam cell formation via simultaneously down-regulating the
      expression of acyl-coenzyme A:cholesterol acyltransferase 1 and up-regulating
      adenosine triphosphate-binding cassette transporter A1.
AB  - BACKGROUND: Ghrelin, an endogenous ligand of the growth hormone secretagogue
      receptor (GHS-R), revealed cardioprotective effects in both experimental models
      and human. There is far less information on the mechanisms that produce
      antiatherogenic effects. We assessed the expression of acyl-coenzyme
      A:cholesterol acyltransferase 1 (ACAT-1) and adenosine triphosphate (ATP)-binding
      cassette transporter A1 (ABCA1), which have been implicated in regulating
      cellular cholesterol homeostasis and therefore play critical roles in foam cell
      formation, in THP-1-derived foam cells in the presence of various concentration
      of ghrelin. METHODS: After 48 h of culture in the presence of phorbol myristate
      acetate, THP-1 monocytes differentiated to macrophages. After another 24 h of
      culture with ox-LDL, the differentiated cells transformed to foam cells.
      Different concentrations of ghrelin and other intervention factors were added,
      respectively. The expression of ACAT-1 and ABCA1 was detected by a technique in
      molecular biology. The content of cellular cholesterol was measured by
      zymochemistry via a fluorospectrophotometer. RESULTS: Ghrelin could down-regulate
      the expression of ACAT-1 and up-regulate the expression of ABCA1 in a dose
      dependent manner simultaneously. Ghrelin also decreased cellular cholesterol
      content and increased cholesterol efflux. These effects could be abolished by the
      specific antagonist of GHS-R and a peroxisome proliferator-activated receptor
      gamma (PPARgamma)-specific inhibitor, respectively. CONCLUSIONS: The results
      suggest that ghrelin inhibited foam cell formation via simultaneously down
      regulating the expression of ACAT-1 and up-regulating ABCA1. Those effects may be
      achieved via pathways involving GHS-R and PPARgamma.

PMID- 19747857
TI  - Pathological study of primary cardiac and pericardial tumours in a specialist UK
      Centre: surgical and autopsy series.
AB  - BACKGROUND: Primary cardiac and pericardial tumours are rare with a prevalence of
      between 0.001% and 0.3%. Thus, general pathologists are not familiar with them.
      Modern advances in cardiac imaging have increased the number of patients
      identified with a primary cardiac tumour in its early stage and also improved
      prognosis. At the Royal Brompton Hospital, London, we did a retrospective study
      to investigate the pathological features of primary cardiac and pericardial
      tumours and compared our findings to other cardiac centres. METHODS: All
      pathologic records at the Royal Brompton Hospital between 1990 and 2008 were
      reviewed to identify patients with a confirmed diagnosis of primary cardiac
      tumours. A total of 94 patients with a histological diagnosis of primary cardiac
      and pericardial tumours were identified and formed the study population. RESULTS:
      The majority (n=67, 71.3%) of cases were benign cardiac tumours. Myxoma was the
      most common histologic type accounting for 27 cases. Among cases with primary
      malignant tumours (n=27, 28.7%), unclassified sarcoma (n=11), leiomyosarcoma
      (n=5), and lymphoma (n=4) were the most common histologic types. CONCLUSION: This
      study, primarily from an adult setting (n=78, 83%) demonstrates a large spectrum
      of cardiac tumours seen in recent cardiologic practice. Myxoma is still the most
      common tumour but more fibroelastomas are being diagnosed due to increased
      imaging.

PMID- 19747858
TI  - Upregulation of CD4 expression during MHC class II-specific positive selection is
      essential for error-free lineage choice.
AB  - The lineage fate of developing thymocytes is determined by the persistence or
      cessation of T cell receptor (TCR) signaling during positive selection, with
      persistent TCR signaling required for CD4 lineage choice. We show here that
      transcriptional upregulation of CD4 expression is essential for error-free
      lineage choice during major histocompatibility complex class II (MHC II)-specific
      positive selection and is critical for error-free lineage choice in TCR
      transgenic mice whose thymocytes compete for the identical selecting ligand. CD4
      upregulation occurred for endogenously encoded CD4 coreceptors, but CD4
      transgenes were downregulated during positive selection, disrupting MHC II
      specific TCR signaling and causing lineage errors regardless of the absolute
      number or signaling strength of transgenic CD4 proteins. Thus, the kinetics of
      CD4 coreceptor expression during MHC II-specific positive selection determines
      the integrity of CD4 lineage choice, revealing an elegant symmetry between
      coreceptor kinetics and lineage choice.

PMID- 19747859
TI  - Small, mobile FcepsilonRI receptor aggregates are signaling competent.
AB  - Crosslinking of IgE-bound FcepsilonRI triggers mast cell degranulation. Previous
      fluorescence recovery after photobleaching (FRAP) and phosphorescent anisotropy
      studies suggested that FcepsilonRI must immobilize to signal. Here, single
      quantum dot (QD) tracking and hyperspectral microscopy methods were used for
      defining the relationship between receptor mobility and signaling. QD-IgE
      FcepsilonRI aggregates of at least three receptors remained highly mobile over
      extended times at low concentrations of antigen that induced Syk kinase
      activation and near-maximal secretion. Multivalent antigen, presented as DNP-QD,
      also remained mobile at low doses that supported secretion. FcepsilonRI
      immobilization was marked at intermediate and high antigen concentrations,
      correlating with increases in cluster size and rates of receptor internalization.
      The kinase inhibitor PP2 blocked secretion without affecting immobilization or
      internalization. We propose that immobility is a feature of highly crosslinked
      immunoreceptor aggregates and a trigger for receptor internalization, but is not
      required for tyrosine kinase activation leading to secretion.

PMID- 19747860
TI  - On the origin of allostasis and stress-induced pathology in farm animals:
      celebrating Darwin's legacy.
AB  - Darwin's largest contribution to science is without doubt the mechanism of
      natural selection, an evolutionary game with players, strategies, and pay-offs.
      Game theory, which attempts to mathematically capture behaviour in situations
      where an organism's success in making choices depends on the choices of others,
      is not only important for economists, but also for biologists, veterinarians and
      other scientists, as it increases understanding of why individual differences
      exist. John Maynard Smith showed that the success of an individual's behaviour
      often depends on others and his Hawk-Dove model is one of the best known examples
      of game theory: the 'hawk' initiates aggressive behaviour (not stopping until
      injured or until the opponent backs down); the 'dove' retreats immediately if the
      opponent initiates aggressive behaviour and will not fight under any
      circumstances. Simultaneous hawkish behaviour has the worst pay-off for both
      players, whereas hawkish behaviour with a dove opponent has the best pay-off.
      Maynard Smith showed that natural selection will work towards an evolutionarily
      stable strategy that, when used by an entire population, is resistant to invasion
      by new mutant strategies. Thus, natural selection actually favours a particular
      ratio of aggressive hawkish and non-aggressive dovish behaviours in order to
      maintain a balance of different characteristics in the population. Natural
      selection has sculpted physiology and behaviour differently in hawks and doves,
      each in their own way so as to maintain stability of the internal environment
      through change--a process which is defined as allostasis. In the short term,
      allostasis has benefits, but in the long run it produces costs. Farm animals have
      been genetically selected by man for increased product quantity and quality, such
      as increased muscle volume, lean meat and egg shell quality, accompanied by
      altered steroid balance (such as more testosterone and less corticosteroids) and
      lower brain monoamine concentrations (serotonin and dopamine). It is hypothesised
      that such genetic selection results in the production of farm animals that prefer
      the hawk behavioural strategy. There is a growing body of evidence that hawk-like
      animals (such as laying hens and pigs) are more vulnerable to the development of
      increased impulsivity and compulsivity (stereotypies) as well as violent
      behaviour.

PMID- 19747861
TI  - Detection of hepatitis E virus in wild boar (Sus scrofa) livers.
AB  - The routes of transmission of hepatitis E virus (HEV) in industrialised countries
      are largely unknown, but several studies suggest that HEV can be a porcine
      zoonosis. The aim of the present study was to determine the prevalence of HEV in
      the wild boar (Sus scrofa) and to determine the genetic relationships between HEV
      sequences recovered from wild boars and from domestic pigs and humans. HEV RNA
      was detected by real time reverse transcriptase PCR in 7/285 (2.5%) liver samples
      from wild boars hunted in South-Eastern France. HEV sequences were recovered from
      five wild boars and belonged to genotype 3f. These sequences shared 89-100%
      nucleotide identity with each other and were genetically close to HEV sequences
      recovered from humans in Southern France. Wild boars in South-Eastern France may
      be a source of HEV transmission to humans.

PMID- 19747862
TI  - Widespread retinal degenerative disease mutation (rdAc) discovered among a large
      number of popular cat breeds.
AB  - The recent discovery of a mutational variant in the CEP290 gene (CEP290:
      IVS50+9T>G), conferring recessive retinal degeneration in Abyssinian and Somali
      (long-haired Abyssinian) cats (rdAc) prompted a survey among 41 cat breeds (846
      individuals) to assess the incidence, frequency and clinical consequence of rdAc.
      The rdAc allele displayed widespread distribution, observed in 16/43 (37%)
      breeds, exhibiting a high allele frequency (~33%) in North American and European
      Siamese populations. Clinical evaluations demonstrated high concordance between
      rdAc pathology and the CEP290 (IVS50+9T>G) homozygous genotype (P=1.1E-6), with
      clinical disease similar to affected Abyssinians/Somalis. This retinal
      degeneration has not been reported in breeds other than the Abyssinian/Somali and
      poses a significant health risk particularly in the Siamese breed group.
      Alertness of the veterinary community and the present availability of commercial
      diagnostic testing could synergistically enable breeders to reduce the incidence
      of rdAc blindness in pure-bred cat populations.

PMID- 19747863
TI  - The prevalence of bovine viral diarrhoea virus infection in beef suckler herds in
      Scotland.
AB  - Bovine viral diarrhoea (BVD) is an endemic disease of cattle that causes
      substantial losses to both beef and dairy production worldwide. The goal of this
      study was to estimate the prevalence of active BVD virus (BVDV) infection in beef
      suckler herds in Scotland. Information was collected from 301 herds using a
      stratified random sampling design based on agricultural census data. Herds were
      classified as with and without active infection based on the within-herd BVDV
      seroprevalence in young stock using Bayesian finite mixture modelling. This
      method accounted for within- and between-herd variability and allowed for
      classification error by the diagnostic tests. The observed sample data enabled
      the discrimination of three distinct seroprevalence cohorts. The results provided
      evidence of active BVDV infection in 16% of herds and no evidence of recent
      exposure in approximately two thirds of herds. The epidemiological significance
      of the further 16% of herds containing young stock with a median BVDV
      seroprevalence of 26.3-38.5% remains unclear. The fact that a large percentage of
      herds did not show evidence of recent infection is encouraging from an animal
      health and welfare perspective and the study provides a model for the further
      exploration of strategies aimed at BVD control at national level.

PMID- 19747864
TI  - Visna/maedi virus serology in sheep: survey, risk factors and implementation of a
      successful control programme in Aragon (Spain).
AB  - A serological survey of Visna/maedi virus (VMV) infection involving 274,048 sheep
      from 554 flocks was undertaken during 2002-2007 in Aragon, North-East Spain. One
      hundred and two of these flocks enrolled in a VMV control programme to reduce
      seroprevalence by selecting replacement lambs from seronegative dams and gradual
      culling of seropositive sheep. Twenty-five flocks were also visited to collect
      flock management and housing data. All study flocks had seropositive animals and
      52.8% of animals tested were seropositive. Among flocks that joined the control
      programme 66 adopted the proposed measures and reduced seroprevalence
      significantly by between 26.1% and 76.9% whereas the remaining 36 flocks did not
      apply the measures and seroprevalence significantly increased. Seroprevalence
      increased with flock size and the number of days the sheep were housed, and
      decreased with increasing weaning age and shed open area, suggesting a reduced
      risk of VMV infection in sheep associated with better ventilation. At the end of
      the period, 24 flocks were certified as VMV-controlled with a seroprevalence <5%,
      and seven as VMV-free with 0% seroprevalence. These are the first officially
      recognised VMV-free flocks in Spain and represent a nucleus of VMV-free
      replacement animals for other flocks. Moreover, they are evidence of the
      possibility of eliminating VMV infection without resorting to whole-flock
      segregation or culling of seropositive sheep.

PMID- 19747865
TI  - Reliability study in five languages of the translation of the pain behavioural
      scale Doloplus.
AB  - Non-verbal pain assessment scales are useful tools for pain evaluation in persons
      with communication disorders and moderate-severe dementia. The Doloplus was one
      of the first scales to be developed and validated as a pain assessment tool in
      older adults with dementia. This study aims at evaluating the translation of the
      Doloplus scale in five languages, as regards test-retest and inter-rater
      reliability. Results show that both tests are good or excellent for the English,
      Italian, Portuguese and Spanish versions and moderate for the Dutch version.
      These results bring a unique opportunity to include the translated Doloplus scale
      in daily assessment of elderly persons with communication disorders, and future
      studies should focus on enriching the validation of the scale in each language.

PMID- 19747866
TI  - Computational screening and design of traditional Chinese medicine (TCM) to block
      phosphodiesterase-5.
AB  - The traditional Chinese medicines (TCM), Epimedium sagittatum (ESs), Cnidium
      monnieri (CMs), and Semen cuscutae (SCs), were used for treating erectile
      dysfunction since the ancient Han dynasty (202 BC-AD 220). Phosphodiesterase-5
      (PDE-5) is deemed the target protein for inhibition to treat erectile
      dysfunction. In this study, a reliable multiple linear regression (MLR) model (r
      value=0.8484) was used to predict the activities of new candidates which were
      designed from ES, CM, and SC. From docking and pharmacophore analysis, the potent
      candidates among ES, CM, and SC were screened. SC01, SC03, and ES03b were
      predicted to have high potencies based on MLR analysis and high docking scores.
      Additionally, from our analysis, we make the follow conclusion (1) Hydrophobic
      compounds tend to be more potent PDE-5 inhibitors; (2) Because of the big binding
      site, inhibitors with molecular weights over 500 remain potent; (3) From the
      pharmacophore analysis, the features of hydrogen bond acceptors are the basis for
      designing novel inhibitors of PDE-5 and (4) According to MLR analysis, the number
      of ring groups could be up to 6, but the number of aromatic rings was limited to
      4 to be potent. This study offers an alternative way to screen PDE-5 inhibitors
      from TCM and provides a scientific basis for confirming pharmacological actions
      of TCM.

PMID- 19747867
TI  - Daily energy balance in growth hormone receptor/binding protein (GHR -/-) gene
      disrupted mice is achieved through an increase in dark-phase energy efficiency.
AB  - The goal of this study was to examine factors that contribute to energy balance
      in female GHR -/- mice. We measured energy intake, energy expenditure (EE), fuel
      utilization, body mass (M(b)) changes and physical activity in 17month-old female
      GHR -/- mice and their age-matched wild type littermates. The GHR -/- mice were
      smaller, consumed more food per unit M(b), had greater EE per unit M(b) and had
      an increase in 24-h EE/M(b) that was similar to the increase in their surface
      area-to-volume ratio. Locomotor activity (LMA) was reduced in the GHR -/- mice,
      but the energetic cost associated with their LMA was greater than in wild type
      controls. Furthermore, M(b) and LMA were independent explanatory covariates of
      most of the variance in EE, and when adjusted for M(b) and LMA, the GHR -/- mice
      had higher EE during both the light and dark phases of the daily cycle.
      Respiratory quotient was lower in GHR -/- mice during the light phase, which
      indicated a greater utilization of lipid relative to carbohydrate in these mice.
      Additionally, GHR -/- mice had higher ratios of caloric intake to EE at several
      intervals during the dark phase, and this effect was greater and more sustained
      in the final 3h of the dark phase. Therefore, we conclude that GHR -/- mice are
      able to overcome the substantial energetic challenges of dwarfism through several
      mechanisms that promote stable M(b). Relative to wild type mice, the GHR -/- mice
      consumed more calories per unit M(b), which offset the disproportionate increase
      in their daily energy expenditure. While GHR -/- mice oxidized a greater
      proportion of lipid during the light phase in order to meet their energy
      requirements, they achieved greater energy efficiency and storage during the dark
      phase through a combination of higher energy consumption and lower LMA.

PMID- 19747868
TI  - Reassessment of phenylalanine tolerance in adults with phenylketonuria is needed
      as body mass changes.
AB  - Lifelong treatment of phenylketonuria (PKU) includes a phenylalanine (phe)
      restricted diet that provides sufficient phe for growth and maintenance plus phe
      free amino acid formula to meet requirements for protein, energy and
      micronutrients. Phe tolerance (mg phe/kg body weight/day) is the amount of phe
      those with PKU can consume and maintain acceptable blood phe levels; it requires
      individual assessment because of varying phenylalanine hydroxylase activity. The
      objective was to reassess phe tolerance in eight adults with PKU considering phe
      requirements, blood phe levels, genotype and phe tolerance at 5 years of age.
      Subjects had not received a personalized assessment of phe tolerance in several
      years, and five subjects were overweight, body mass index (BMI) 25-28. With the
      guidance of a metabolic dietitian, seven subjects increased phe tolerance (by 15
      173%) without significantly increasing blood phe concentration. Increased phe
      tolerance was associated with both improved dietary compliance and inadequate phe
      intake at the onset of the protocol compared with current requirements. Improved
      dietary compliance reflected increased consumption of protein equivalents from
      amino acid formula and increased frequency of formula intake, from 2.2 to 3 times
      per day. Predictors of higher final phe tolerance following reassessment included
      being male and having a lower BMI (R(2)=0.588). This suggests that the rising
      trend of overweight and obesity may affect assessment of phe tolerance in adults.
      Therefore, interaction with the metabolic dietitian to reassess phe tolerance in
      relation to body mass is essential throughout adulthood to insure adequate intake
      of phe to support protein synthesis and prevent catabolism.

PMID- 19747869
TI  - Supervised home-based exercise may attenuate the decline of glucose tolerance in
      obese pregnant women.
AB  - AIM: The significant deterioration of insulin sensitivity and glucose tolerance
      during pregnancy can have serious health implications for both the pregnant woman
      and her baby. Although it is well established that regular exercise benefits
      insulin sensitivity in the nonpregnant population, the effect on glucose
      tolerance in obese pregnant women is not known. The purpose of this study was to
      investigate the effect of a supervised 10-week, home-based, exercise programme,
      beginning at week 18 of gestation, on glucose tolerance and aerobic fitness in
      previously sedentary obese women. METHODS: Twelve sedentary obese women were
      randomized into an exercise (EX; n=6) or control (CON; n=6) group at 18 weeks of
      gestation. Those randomized to EX engaged in 10 weeks of supervised home-based
      exercise (three sessions a week of stationary cycling), while those in the CON
      group maintained their usual daily activity. Their glucose and insulin responses
      to an oral glucose tolerance test (OGTT), as well as their aerobic fitness, were
      assessed both pre- and postintervention. RESULTS: Reduced glucose tolerance in
      the CON, but not EX, group was indicated by a tendency postintervention towards
      higher blood glucose levels at 1h of the OGTT (P=0.072). Furthermore, at 2h of
      the postintervention OGTT, blood glucose tended to remain elevated from baseline
      in the CON (P=0.077). There was also a trend towards increased fitness in the EX
      (P=0.064), but not the CON group. CONCLUSION: Regular aerobic exercise begun
      during pregnancy may have favourable effects on glucose tolerance and fitness in
      obese women, and warrants further investigation in a larger sample population.

PMID- 19747870
TI  - A new effect of ultrasonication on the formation of BaTiO(3) nanoparticles.
AB  - A new effect of ultrasonic irradiation on the formation of BaTiO(3) particles was
      identified. Ultrasonication caused the aggregation of the original 5-10nm
      BaTiO(3) particles in the same crystal axis and accelerated the formation of
      BaTiO(3) particles significantly. Furthermore, narrow size distribution was
      obtained for the aggregated particles under ultrasonic irradiation.

PMID- 19747871
TI  - Modeling upper airway collapse by a finite element model with regional tissue
      properties.
AB  - This study presents a new computational system for modeling the upper airway in
      rats that combines tagged magnetic resonance imaging (MRI) with tissue material
      properties to predict three-dimensional (3D) airway motion. The model is capable
      of predicting airway wall and tissue deformation under airway pressure loading up
      to airway collapse. The model demonstrates that oropharynx collapse pressure
      depends primarily on ventral wall (tongue muscle) elastic modulus and airway
      architecture. An iterative approach that involves substituting alternative
      possible tissue elastic moduli was used to improve model precision. The proposed
      3D model accounts for stress-strain relationships in the complex upper airway
      that should present new opportunities for understanding pathogenesis of airway
      collapse, improving diagnosis and developing treatments.

PMID- 19747872
TI  - Wrist pulse signal diagnosis using modified Gaussian models and Fuzzy C-Means
      classification.
AB  - Wrist pulse signal contains important information about the health status of a
      person and pulse signal diagnosis has been employed in oriental medicine for
      thousands of years. In this research, a systematic approach is proposed to
      analyze the computerized wrist pulse signals, with the focus placed on the
      feature extraction and pattern classification. The wrist pulse signals are first
      collected and pre-processed. Considering that a typical pulse signal is composed
      of periodically systolic and diastolic waves, a modified Gaussian model is
      adopted to fit the pulse signal and the modeling parameters are then taken as
      features. Consequently, a feature selection scheme is proposed to eliminate the
      tightly correlated features and select the disease-sensitive ones. Finally, the
      selected features are fed to a Fuzzy C-Means (FCM) classifier for pattern
      classification. The proposed approach is tested on a dataset which includes pulse
      signals from 100 healthy persons and 88 patients. The results demonstrate the
      effectiveness of the proposed approach in computerized wrist pulse diagnosis.

PMID- 19747873
TI  - South Asian migrant women and HIV/STIs: knowledge, attitudes and practices and
      the role of sexual power.
AB  - Differences in relationship power dynamics or migration factors may affect
      knowledge, attitudes, and practices (KAP) towards HIV/AIDS and sexually
      transmitted infections (STIs) in resettling Migrant women. A sample of 122 women
      and men born in India, Sri Lanka, Pakistan or Bangladesh and residing in Montreal
      completed questionnaires on HIV/STI KAP and decision-making power Within sexual
      relationships. Knowledge gaps and stigmatizing attitudes were found. STI/HIV
      information available in one's language and other educational strategies that
      consider women's Power may improve KAP among South Asian migrant women.

PMID- 19747874
TI  - Hexosamine analogs: from metabolic glycoengineering to drug discovery.
AB  - Metabolic glycoengineering, a technique pioneered almost two decades ago wherein
      monosaccharide analogs are utilized to install non-natural sugars into the
      glycocalyx of mammalian cells, has undergone a recent flurry of advances spurred
      by efforts to make the methodology more efficient. This article describes the
      versatility of metabolic glycoengineering, which is a prime example of 'chemical
      glycobiology,' and gives an overview of its capability to endow complex
      carbohydrates in living cells and animals with interesting (and useful!)
      functionalities. Then an overview is provided describing how acylated
      monosaccharides, a class of molecules originally intended to be efficiently-used,
      membrane-permeable metabolic intermediates, have led to the discovery that a
      subset of these compounds (e.g. tributanoylated hexosamines) display
      unanticipated 'scaffold-dependent' activities; this finding establishes these
      molecules as a versatile platform for drug discovery.

PMID- 19747875
TI  - UV/blue upconversion in Nd3+:TeO2 glass, effect of modifiers and heat treatment
      on the fluorescence bands.
AB  - Upconversion (UC) emissions in UV/blue region have been observed in Nd(3+) doped
      tellurite glass on 532 nm excitation. The UC bands have been observed at 360,
      387, 417 and 452 nm due to the (4)D(3/2)-->(4)I(9/2), (4)D(3/2)-->(4)I(11/2),
      (4)D(3/2)-->(4)I(13/2) and (4)D(3/2)-->(4)I(15/2) transitions, respectively and
      they show two photon character. The effect of BaCO(3), BaF(2) and BaCl(2) glass
      modifiers on the UC efficiency has been studied and Judd-Ofelt intensity
      parameters have been calculated and compared. The BaCl(2) modified glass showed
      maximum UC intensity among the three modifiers and this enhancement in UC
      intensity has been related to the reduction in average phonon frequency of the
      glass sample. Heat treatments of the BaF(2) and BaCl(2) modified samples also
      show enhancement in UC intensity while the BaCO(3) modified sample has no such
      effect. Lifetime of the (4)D(3/2) level has been measured to understand the
      mechanism responsible for UC emission. Temperature dependent fluorescence studies
      have been done on the (4)F(3/2), (4)F(5/2) and (2)S(3/2) emitting levels and
      results show that Nd(3+) doped tellurite glass can be used as a temperature
      sensor.

PMID- 19747876
TI  - Dexamethasone-based therapy for childhood acute lymphoblastic leukaemia: results
      of the prospective Dutch Childhood Oncology Group (DCOG) protocol ALL-9 (1997
      2004).
AB  - BACKGROUND: A population-based cohort of children aged 1-18 years with acute
      lymphoblastic leukaemia (ALL) was treated with a dexamethasone-based protocol
      (Dutch Childhood Oncology Group [DCOG] ALL-9). We aimed to confirm the results of
      the most effective DCOG ALL protocol for non-high-risk (NHR) patients to date
      (ALL-6), compare results with ALL-7 and ALL-8, and study prognostic factors in a
      non-randomised setting. METHODS: From Jan 1, 1997, until Nov 1, 2004, patients
      with ALL were treated according to the ALL-9 protocol in eight Dutch academic
      centres with their affiliated peripheral hospitals. Patients were stratified into
      NHR and high risk (HR) groups. HR criteria were white-blood-cell count of 50,000
      cells per microL or more, T-cell phenotype, mediastinal mass, CNS or testicular
      involvement, and Philadelphia chromosome or MLL rearrangement; patients who did
      not fulfil these criteria were deemed to be NHR. The NHR group was treated with a
      three-drug induction (dexamethasone, vincristine, and asparaginase) for 6 weeks,
      medium-dose methotrexate for 3 weeks, then maintenance therapy. HR patients
      received a four-drug induction (as for the NHR patients plus daunorubicin) for 6
      weeks, high-dose methotrexate for 8 weeks, and two intensification courses before
      receiving maintenance therapy. Triple intrathecal medication was given 13 times
      in NHR patients, 15 times in HR patients (17 times for patients with initial CNS
      involvement). No patient received cranial irradiation. Maintenance therapy was
      given until 109 weeks for all patients and consisted of mercaptopurine and
      methotrexate for 5 weeks, alternated with dexamethasone and vincristine for 2
      weeks. Kaplan-Meier analysis was done on an intention-to-treat basis with event
      free survival as the primary endpoint. This trial is registered at
      trialregister.nl, number NTR460/SNWLK-ALL-9. FINDINGS: 859 patients were
      recruited to the study. Complete remission was achieved in 592 (98.5%) of the 601
      patients in the NHR group and 250 (96.9%) of the 258 in the HR group. Five
      patients in the NHR group and four in the HR group died during induction. Median
      follow-up for patients alive was 72.2 (range 4.8-132.7) months as of August,
      2008. 5-year event-free survival was 81% (SE 1%) in all patients: 84% (2%) in NHR
      patients, and 72% (3%) in HR patients. Isolated CNS relapses occurred in 22
      (2.6%) of 842 patients. In a multivariate analysis, DNA index was the strongest
      predictor of outcome (<1.16 vs >or=1.16; relative risk 0.42, 95% CI 0.22-0.78),
      followed by age (1-9 vs >or=10 years; 2.23, 1.60-3.11) and white-blood-cell count
      (<50,000 vs >or=50,000 cells per microL; 1.60, 1.13-2.26). INTERPRETATION: The
      overall results of the dexamethasone-based DCOG ALL-9 protocol are better than
      those of our previous Berlin-Frankfurt-Munster-based protocols ALL-7 and ALL-8.
      The results for NHR patients were achieved with high cumulative doses of
      dexamethasone and vincristine, but without the use of anthracyclines, etoposide,
      cyclophosphamide, or cranial irradiation, therefore minimising the risk of side
      effects. FUNDING: Dutch Health Insurers.

PMID- 19747877
TI  - Prophylactic cranial irradiation: going, going, gone.

PMID- 19747878
TI  - Functional immunoassays using an in-vitro malaria liver-stage infection model:
      where do we go from here?
AB  - For more than 25 years, the ISI assay and ILSDA have been used to study the
      development of the malaria parasite in the liver, to discover and characterize
      sporozoite and liver-stage antigens, to support the development of malaria
      vaccine candidates, and to search for immunological correlates of protection in
      animals and in humans. Although both assays have been limited by low sporozoite
      invasion rates, significant biological variability, and the subjective nature of
      manually counting hepatocytes containing parasites as the read-out, they have
      nevertheless been useful tools for exploring parasite biology. This review
      describes the origin, application and current status of these assays, critically
      discusses the need for improvements, and explores the roles of these assays in
      supporting the development of an effective vaccine against Plasmodium falciparum
      malaria.

PMID- 19747879
TI  - Plasmodium falciparum biology: analysis of in vitro versus in vivo growth
      conditions.
AB  - Recent studies of Plasmodium falciparum isolated directly from infected patients
      indicate that alternative parasite biological states occur in the natural host
      that are not observed with in vitro cultivated parasites. Variation in host
      substrates, immune responses and other factors probably induce modifications in
      parasite biology. These biological states could have important implications for
      pathogenesis, transmission and therapy. We review the differences between P.
      falciparum in vitro culture systems and in vivo host environments, as well as
      evidence that host conditions can alter pathogen biology. For select biological
      questions, the incorporation of naturally occurring conditions into in vitro
      experimental manipulation of microbes may provide novel insight into pathogen
      biology.

PMID- 19747880
TI  - The heart of darkness: growth and form of Trypanosoma brucei in the tsetse fly.
AB  - The first description of African trypanosomes was made over a century ago. The
      importance of the tsetse in transmission and cyclic development of trypanosomes
      was discovered soon afterwards, and has been the focus of numerous studies since.
      However, investigation of trypanosomes in tsetse flies requires high resource
      investment and unusual patience; hence, many facets of trypanosome biology in the
      tsetse remain to be characterised despite the long history of research. Here,
      current knowledge and questions about some of the developmental changes in
      trypanosomes that occur in tsetse flies are summarised, along with recent
      technical advances that can now be used to provide some answers.

PMID- 19747881
TI  - Rwanda: A thousand hills, a thousand dreams, a thousand challenges for nurses and
      midwives and the Millennium Development Goals.

PMID- 19747882
TI  - Direct medical costs for patients seeking emergency care for losses of epilepsy
      control in a U.S. managed care setting.
AB  - The objective of this retrospective claims database study was to compare the
      costs of care from a U.S. payer perspective before and after epilepsy treatment
      in emergent care settings and, secondarily, to describe the frequency of toxic
      effects and physical injuries occurring on the date of the emergent care. Nine
      and four-tenths percent of patients receiving emergent care for epilepsy
      (114/1213) had an injury or adverse antiepileptic drug effect on the same date.
      The majority of incidents were superficial injuries and contusions (28%),
      fractures (21%), open wounds or injury to blood vessels (19%), intracranial
      injury (10%), and/or medication toxicity (10%). Both non-epilepsy-related
      (US$12,745.56) and epilepsy-related (US$2013.62) direct medical costs of care pre
      index were significantly different from those post-index (US$15,274.95 and
      US$7087.53, respectively). The cost of care for possible reestablishment of
      epilepsy control and treatment of co-occurring injuries is significant when
      compared with that for the period prior to seizure.

PMID- 19747883
TI  - In-session seizures during low-frequency repetitive transcranial magnetic
      stimulation in patients with epilepsy.
AB  - Low-frequency repetitive transcranial magnetic stimulation (rTMS) is emerging as
      a therapeutic tool for patients with intractable epilepsy. Although seizures
      during treatment have been reported as adverse events in some patients, the
      nature and severity of seizures that may be provoked by low-frequency rTMS in
      patients with epilepsy have not been extensively studied. Accordingly, this
      article documents seizures in patients (n=5) with intractable epilepsy and
      average seizure frequency greater than one per day who underwent 1-Hz rTMS for
      seizure suppression. We report three observations in the present case series: (1)
      in each instance the in-session seizure was typical in semiology to the patient's
      habitual seizures, (2) the duration of each documented seizure was either the
      same as or shorter than the patients' baseline seizures, and (3) the overall
      neurological outcome on follow-up was not affected by the in-session seizures.
      More data will be required for valid conclusions with respect to safety and
      tolerability of low-frequency rTMS in patients with epilepsy, but it is
      noteworthy from our perspective that seizures during rTMS in this series were
      similar to the patients' habitual seizures, occurred in patients with epilepsy
      with baseline seizure frequency exceeding one per day, and did not correlate with
      a poor neurological outcome or with absence of clinical response to rTMS.

PMID- 19747884
TI  - Cardiovascular complications of obesity surgery in patients with increased
      preoperative cardiac risk.
AB  - BACKGROUND: Obesity surgery reduces the incidence of long-term cardiovascular
      events by modifying the associated risk factors. The derived benefits of weight
      loss surgery might be counterbalanced by the increased cardiovascular risks in
      some patients. The primary objective of the present study was to determine the
      rate of cardiovascular events after obesity surgery in patients considered to
      have an increased cardiac risk profile at a tertiary referral hospital. METHODS:
      A retrospective analysis of the data from consecutive patients who underwent
      obesity surgery at the Cleveland Clinic Florida was performed. The use of beta
      blockers, noninvasive stress testing, and perioperative events were assessed.
      RESULTS: The data from 154 patients who had undergone a preoperative cardiac
      consultation at the Cleveland Clinic Florida before obesity surgery from 2003 to
      2006 were analyzed. Most patients were women (n = 108, 69%), and 25 (16%) were
      >65 years old. The number of patients who received perioperative beta-blockers
      was 72 (47%). Noninvasive stress testing was performed in 78 patients (50%). Of
      the 78 patients who underwent noninvasive stress testing, 25 (32%) had a positive
      finding. Only 1 patient with positive stress test results had an obstructive
      coronary artery lesion found on cardiac catheterization. A total of 5 nonfatal
      cardiac-related events (3.2%) occurred. The in-hospital mortality rate was 0%.
      CONCLUSION: Obesity surgery in patients with established coronary heart disease
      or risk factors is a safe and well-tolerated procedure, with an overall low rate
      of cardiac events. Noninvasive stress testing in this population resulted in a
      high rate of false-positive results and uncommonly led to intervention.

PMID- 19747885
TI  - The Hurst exponent of cardiac response to positive and negative emotional film
      stimuli using wavelet.
AB  - We examined the Hurst exponent of heart rate time series and its relation with
      the subjective measures of valence and arousal in two groups of subjects. The
      electrocardiogram (ECG) and the subjective valence and arousal were measured
      during the administration of emotional film stimuli (happiness, sadness, anger
      and fear). The results showed that there is a difference in the Hurst exponent
      for the happiness and sadness conditions but not between the negative emotion
      conditions (sadness, anger and fear). This seems to indicate that the Hurst
      exponent is an indicator of subjective valence.

PMID- 19747886
TI  - Structural basis for the lack of opposite base specificity of Clostridium
      acetobutylicum 8-oxoguanine DNA glycosylase.
AB  - 7,8-Dihydro-8-oxoguanine (8-oxoG) is the major oxidative product of guanine and
      the most prevalent base lesion observed in DNA molecules. Because 8-oxoG has the
      capability to form a Hoogsteen pair with adenine (8-oxoG:A) in addition to a
      normal Watson-Crick pair with cytosine (8-oxoG:C), this lesion can lead to a G:C-
      >T:A transversion after replication. However, 8-oxoG is recognized and excised by
      the 8-oxoguanine DNA glycosylase (Ogg) of the base excision repair pathway.
      Members of the Ogg1 family usually display a strong preference for a C opposite
      the lesion. In contrast, the atypical Ogg1 from Clostridium actetobutylicum
      (CacOgg) can excise 8-oxoG when paired with either one of the four bases, albeit
      with a preference for C and A. Here we describe the first high-resolution crystal
      structures of CacOgg in complex with duplex DNA containing the 8-oxoG lesion
      paired to cytosine and to adenine. A structural comparison with human OGG1
      provides a rationale for the lack of opposite base specificity displayed by the
      bacterial Ogg.

PMID- 19747887
TI  - Aminoglycoside therapy against Pseudomonas aeruginosa in cystic fibrosis: a
      review.
AB  - In patients with cystic fibrosis (CF), respiratory infections with the
      opportunistic bacterial pathogen Pseudomonas aeruginosa have a major impact on
      morbidity and mortality. Aminoglycosides, especially tobramycin, have been used
      successfully to combat these infections. Aminoglycoside penetration of bronchial
      secretions is poor when the antibiotic is administered intravenously.
      Nebulization allows direct delivery of the drug to the sites of infection within
      the airways, while avoiding systemic exposure. Published clinical data show that
      inhaled tobramycin reduces the bacterial load, improves lung function and reduces
      the number of hospital admissions. Inhaled tobramycin has been used successfully
      to eradicate P. aeruginosa in patients with early infection. Maintaining clinical
      benefits requires chronic tobramycin treatment, and the concept of chronic
      intermittent inhaled treatment (typically, alternating drug and drug-free periods
      of 28 days) was introduced to minimize the emergence of aminoglycoside resistant
      P. aeruginosa strains. Other therapeutic advances include the development of
      different tobramycin formulations and nebulizers that reduce delivery time
      without compromising efficacy. An optimal treatment regimen for patients with CF
      with early or intermittent P. aeruginosa infections remains a high priority to
      maintain long-term lung health.

PMID- 19747889
TI  - The 'new' bronchopulmonary dysplasia: challenges and commentary.
AB  - Lung development is orchestrated by highly integrated morphogenic programs of
      interrelated patterns of gene and protein expression. Injury to the developing
      lung in the canalicular and saccular phases of lung development alters subsequent
      alveolar and vascular development resulting in simplified alveolar structures,
      dysmorphic capillary configuration, variable interstitial cellularity and
      fibroproliferation that are characteristic of the 'new' bronchopulmonary
      dysplasia (BPD). Fetal and neonatal infection, abnormal stretch of the developing
      airways and alveoli, altered expression of surfactant proteins (or genetically
      altered proteins), polymorphisms of genes encoding for vascular endothelial
      growth factors, and reactive oxygen species result in imparied gas exchange in
      the developing lung. However, the 'new' BPD represents only one form of neonatal
      chronic lung disease and the consistent use of both the physiologic definition
      and severity scale would provide greater accuracy in determining the impact of
      the disease currently defined by its treatment. Our present labelling of the
      clinical state of oxygen supplementation and/or ventilatory support at 36 weeks'
      postmenstrual age and the histopathologic severity of alveolar arrest and
      vascular 'simplification' may not always be predictive of the degree of altered
      lung development and thus longer-term pulmonary function evaluations are needed
      to determine the impact of this disorder in specific infants. The proposed role
      of novel molecular therapies, and the combined effects of currently established
      therapies, as well as exogenous surfactant and inhaled nitric oxide or repetitive
      surfactant dosing, on the severity and incidence of new BPD hold considerable
      promise for reducing the long-term pulmonary morbidity among infants delivered
      prematurely.

PMID- 19747888
TI  - Participation in colorectal cancer screening with FOBT and colonoscopy: an
      Italian, multicentre, randomized population study.
AB  - BACKGROUND: Data on the adherence rate to screening colonoscopy (OC) in the
      average-risk general population are limited and variable. Aim of this study was
      to compare the uptake of OC screening with that of fecal occult blood (FOBT).
      METHODS: A nationwide, population-based, multicentre, randomized trial comparing
      attendance to OC with that to FOBT was performed. Sixty-four general
      practitioners (GPs), overall including in their lists 9889 average-risk subjects
      aged 55-64 years, were randomized between OC and FOBT screening programs.
      Eligible subjects were mailed a personal invitation letter co-signed by their GP
      and the coordinator of the area-reference GI centre. Attendance rate and
      detection rate for advanced neoplasia (colorectal cancer, adenoma >10mm or with
      villous histology or high-grade dysplasia) for each arm of the study were
      assessed. RESULTS: The overall attendance rate was 18.7% (1563/8378 eligible
      subjects). It was markedly lower in the OC than in the FOBT strategy (10% vs.
      27.1%; OR 0.28, 95% CI: 0.25-0.32; P<0.0001). In particular, participation in OC
      screening arm was extremely low in South Italy (2.8%), whilst it was higher in
      North-Central Italy (12.4%; P<0.0001). Compliance to colonoscopy in those with a
      positive FOBT was only 58%. Advanced neoplasia was detected in 28 (6.8%) patients
      in the OC arm and in 6 (18%) in those with a positive FOBT submitted to OC.
      CONCLUSIONS: The results of our study underline the difficulties and barriers to
      implement a OC population screening in Italy, at least through primary care.
      Although attendance to FOBT was higher, it was disappointingly less than 30%.
      Significant actions to improve awareness amongst GPs and the population are a
      high priority.

PMID- 19747890
TI  - Drug therapies in bronchopulmonary dysplasia: debunking the myths.
AB  - Bronchopulmonary dysplasia (BPD), also known as chronic lung disease (CLD), is
      one of the most challenging complications in premature infants. The incidence of
      BPD has been increasing over the past two decades in parallel with an improvement
      in the survival of this population. Furthermore, the clinical characteristics and
      the natural history of infants affected by BPD have changed considerably, and
      newer definitions to clarify the term 'BPD' have also evolved since its first
      description more than four decades ago. Several drug therapies have also evolved,
      either to manage these infants' respiratory distress syndrome with an aim to
      prevent BPD or to manage the established condition. Although there is good
      evidence to support the 'routine' use of some therapies, many other therapies
      currently used in relation to BPD remain individual- or institution-specific,
      depending on beliefs and myths that we have adopted. In this article, we discuss
      the importance of defining BPD more objectively and the support--or lack thereof-
      for the drug therapies used in relation to BPD.

PMID- 19747891
TI  - Clinical practice guidelines for the management of meniscal lesions and isolated
      lesions of the anterior cruciate ligament of the knee in adults.
AB  - CONTEXT: Meniscal lesions and isolated anterior cruciate ligament (ACL) knee
      injuries are common. In 2006, about 130,000 patients were admitted to hospital
      for meniscal surgery and 35,000 for ACL surgery in France. Surgical techniques
      and indications have evolved over recent years, and interest in meniscus
      preservation has increased due to the higher risk of femorotibial osteoarthritis
      following meniscectomy. OBJECTIVES: To encourage good practices in meniscal
      lesions surgery (particularly meniscus preservation) and to clarify indications
      and techniques in ACL reconstruction surgery. METHODS: A systematic review of the
      literature (1996-2007) was performed. It was submitted to a multidisciplinary
      working group of experts in the field (n=10) who drafted an evidence report and
      clinical practice guidelines which were subsequently amended in the light of
      comments from 50 peer reviewers. MAIN RECOMMENDATIONS: (i) Meniscal repair should
      only be used to heal peripheral meniscal lesions affecting healthy meniscal
      tissue (injury) in vascularised areas (red-red zone or red-white zone). The
      current trend is towards use of hybrid implants (fixation material combined with
      suture wire) and an exclusively arthroscopic technique. (ii) Traumatic meniscal
      lesions do not always require a meniscectomy; no surgery or meniscal repair
      should systematically be considered. (iii) The assessment and management of non
      traumatic degenerative meniscal lesions depend on the extent of cartilage damage.
      (iv) All ACL ruptures do not require reconstructive surgery. The indication for
      reconstruction is based on symptoms, in particular functional instability. As far
      as acute ACL injuries are considered, reconstruction by arthroscopy should
      preferably be delayed to reduce the thromboembolic events or joint stiffness. (v)
      Bone-tendon-bone graft and hamstring tendon reconstruction give similar results.
      (vi) Lateral tenodesis should be limited to specific cases.

PMID- 19747892
TI  - Chronic neck pain and vertigo: Is a true balance disorder present?
AB  - OBJECTIVE: We sought to establish whether chronic neck pain patients suffering
      from vertigo and instability have true balance disorders. PATIENTS AND METHODS:
      Ninety-two patients having suffered from chronic neck pain for at least 3 months
      were enrolled in the present study. Patients with a history of neck trauma or
      ear, nose and throat, ophthalmological or neurological abnormalities were
      excluded. The patients were evaluated in a clinical examination (neck mobility)
      and a test of dynamic and static balance on the Satel((R)) platform in which
      mediolateral (Long X) and anterior-posterior deviations (Long Y) were monitored.
      Our patients were divided into three groups: a group of 32 patients with neck
      pain and vertigo (G1), a group of 30 patients with chronic neck pain but no
      vertigo (G2) and a group of 30 healthy controls. RESULTS: All groups were
      comparable in terms of age, gender, weight and shoe size. Osteoarthritis was
      found in 75% and 70% of the subjects in G1 and G2, respectively. Neck-related
      headache was more frequent in G1 than in G2 (65.5% versus 40%, respectively;
      p=0.043). Restricted neck movement was more frequent in G1 and concerned flexion
      (p<0.001), extension (p<0.001), rotation (p<0.001), right inclination (p<0.001)
      and left inclination (p<0.001). Balance abnormalities were found more frequently
      in G1 than in G2 or G3. Static and dynamic posturographic assessments (under
      "eyes open" and "eyes shut" conditions) revealed abnormalities in statokinetic
      parameters (Long X and Long Y) in G1. CONCLUSION: Our study evidenced abnormal
      static and dynamic balance parameters in chronic neck pain patients with vertigo.
      These disorders can be explained by impaired cervical proprioception and neck
      movement limitations. Headache was more frequent in these patients.

PMID- 19747893
TI  - Impact of an educational video-based strategy on the behavior process associated
      with colorectal cancer screening: a randomized controlled study.
AB  - BACKGROUND: Low public awareness is an important barrier for colorectal cancer
      screening participation. AIM: To evaluate the impact of educational intervention
      on the health behavior process, patient knowledge and compliance with colorectal
      cancer screening in the average-risk population. METHODS: 158 subjects (aged 50
      79 years) were randomly assigned either to watch a non-medical video or a
      colorectal cancer educational video. Before and after watching the experimental
      or control videotape, participants completed a five-item questionnaire that
      assessed their knowledge about risk factors for colorectal cancer, age of risk,
      warning symptoms, 5-year prognosis, and incidence. Subjective risk perception for
      developing colorectal cancer, barriers or benefits of screening, and intention to
      be screened were also investigated. Finally, subjects received a faecal occult
      blood test kit and were requested to use and return it within 2 weeks. RESULTS:
      Participants in the video-based intervention group showed significant improvement
      in knowledge of colorectal cancer scores (P<0.001) and decreased barrier scores.
      The intervention group returned significantly more faecal occult blood tests than
      controls (69.6% vs. 54.4%, P=0.035). The intervention had a positive effect on
      modifying attitudes and intention to take part in screening. Additionally, the
      intervention was a predictor of compliance (OR 2.0; 95% CI=1.02-3.84, P=0.044).
      CONCLUSION: Video-based intervention significantly reduced barriers to screening
      and improved participant awareness and compliance with colorectal cancer
      screening with faecal occult blood test.

PMID- 19747894
TI  - Structure-function studies on the voltage-gated sodium channel.
AB  - Recent research on structure-function relationships aspects of voltage-gated
      sodium channels (VGSCs) are reviewed. Data issued from the literature are
      summarized and compared, including results from our own studies. The latter deal
      with the effects of drug binding, deglycosylation and the role of hydrophobic
      residues in the voltage sensors. Methods mainly consist of circular dichroism
      (CD) to asses the channel's secondary structure and conductance measurements
      after reconstitution into planar lipid bilayers. Molecular modelling was also
      used to tentatively explain experimental data. Since 30% of the channel's mass
      are glycoconjugates, the effects of removing them were first investigated. Then,
      the effects of the neurotoxin Batrachotoxin and the anticonvulsant Lamotrigine
      were studied. Both drugs induced a significant increase in the channel's helical
      content and a molecular model shows that lamotrigine interacts with residues
      previously identified as forming the binding sites in the pore. Finally, the role
      of hydrophobic residues with long sidechains in the voltage sensors (S4s) was
      investigated. Recent research on related studies on VGSCs are discussed.

PMID- 19747895
TI  - Solution structure of the E. coli ribosome hibernation promoting factor HPF:
      Implications for the relationship between structure and function.
AB  - The 70S Escherichia coli ribosome dimerizes to form an inactive 100S ribosome
      during stationary phase, which is called "ribosome hibernation". The hibernation
      promoting factor HPF plays a crucial role in 100S ribosome formation. However,
      YfiA, a known paralog of HPF inhibits 100S formation, although it shares high
      sequence similarity. Here, we report the first solution structure of HPF as
      determined by multi-dimensional NMR. HPF adopts betaalphabetabetabetaalpha-fold
      and the overall structure is similar to YfiA as expected. However, detailed
      structure comparison based on the determined structure in this study revealed
      that there are remarkable differences around the C-terminal portion of helix
      alpha2, which is not predicted by homology modeling. Furthermore, some acidic
      residues conserved only in HPF are located at the rim of the common basic patch.

PMID- 19747896
TI  - Activation of AMP-activated protein kinase (AMPK) inhibits fatty acid synthesis
      in bovine mammary epithelial cells.
AB  - Activation of AMP-activated protein kinase (AMPK), a heterotrimeric energy
      sensing protein, decreases lipid synthesis in liver tissue of various species;
      however, little is known about the role of AMPK in the regulation of fatty acid
      synthesis in bovine mammary epithelial cells. Here we report the presence of AMPK
      mRNA in MAC-T bovine mammary epithelial cells and mammary gland. Treatment of MAC
      T with an AMPK activator dramatically decreased de novo fatty acid synthesis by
      inactivating acetyl-CoA carboxylase-alpha. Activation of AMPK also modified the
      mRNA expression of several lipogenic genes including fatty acid synthase,
      glycerol-3-phosphate acyltransferase, and fatty acid binding protein-3.
      Additionally, decreases in energy availability or rises in intracellular Ca(2+)
      most likely activated AMPK in MAC-T. These data suggest the presence of LKB1 and
      Ca(2+)/calmodulin-dependent kinase kinase, two known AMPK kinases, in MAC-T.
      Identifying AMPK as a molecular target capable of modifying energy substrate
      utilization may result in the development of new technologies that increase milk
      production or modify milk composition during periods of increased energy demand.

PMID- 19747897
TI  - A role for nuclear translocation of tripeptidyl-peptidase II in reactive oxygen
      species-dependent DNA damage responses.
AB  - Responses to DNA damage are influenced by cellular metabolism through the
      continuous production of reactive oxygen species (ROS), of which most are by
      products of mitochondrial respiration. ROS have a strong influence on signaling
      pathways during responses to DNA damage, by relatively unclear mechanisms.
      Previous reports have shown conflicting data on a possible role for tripeptidyl
      peptidase II (TPPII), a large cytosolic peptidase, within the DNA damage
      response. Here we show that TPPII translocated into the nucleus in a p160-ROCK
      dependent fashion in response to gamma-irradiation, and that nuclear expression
      of TPPII was present in most gamma-irradiated transformed cell lines. We used a
      panel of nine cell lines of diverse tissue origin, including four lymphoma cell
      lines (T, B and Hodgkins lymphoma), a melanoma, a sarcoma, a colon and two breast
      carcinomas, where seven out of nine cell lines showed nuclear TPPII expression
      after gamma-irradiation. Further, this required cellular production of ROS;
      treatment with either N-acetyl-Cysteine (anti-oxidant) or Rotenone (inhibitor of
      mitochondrial respiration) inhibited nuclear accumulation of TPPII. The local
      density of cells was important for nuclear accumulation of TPPII at early time
      points following gamma-irradiation (at 1-4h), indicating a bystander effect.
      Further, we showed that the peptide-based inhibitor Z-Gly-Leu-Ala-OH, but not its
      analogue Z-Gly-(D)-Leu-Ala-OH, excluded TPPII from the nucleus. This correlated
      with reduced nuclear expression of p53 as well as caspase-3 and -9 activation in
      gamma-irradiated lymphoma cells. Our data suggest a role for TPPII in ROS
      dependent DNA damage responses, through alteration of its localization from the
      cytosol into the nucleus.

PMID- 19747898
TI  - Mechanical stretch enhances IL-8 production in pulmonary microvascular
      endothelial cells.
AB  - In patients with acute respiratory distress syndrome, mechanical over-distension
      of the lung by a large tidal volume causes further damage and inflammation,
      called ventilator-induced lung injury (VILI), however, it is unclear how
      mechanical stretch affects the cellular functions or morphology in human
      pulmonary microvascular endothelial cells (HPMVECs). IL-8 has been proposed to
      play an important role in the progression of VILI by activating neutrophils. We
      demonstrated that HPMVECs exposed to cyclic uni-axial stretch produce IL-8
      protein with p38 activation in strain- and time-dependent manners. The IL-8
      synthesis was not regulated by other signal transduction pathways such as ERK1/2,
      JNK, or stretch-activated Ca(2+) channels. Moreover, cyclic stretch enhanced IL-6
      and monocyte chemoattractant protein-1 production and reoriented cell
      perpendicularly to the stretch axis accompanied by actin polymerization. Taken
      together, IL-8 production by HPMVECs due to excessive mechanical stretch may
      activate neutrophilic inflammation, which leads to VILI.

PMID- 19747899
TI  - Long-term cognitive impairment and myelination deficiency in a rat model of
      perinatal hypoxic-ischemic brain injury.
AB  - Although periventricular white matter injury is a leading cause of major
      neurologic disability in premature infants, the relationship between myelination
      deficiency and long-term cognitive dysfunction is not well understood. The
      purpose of this study was to investigate oligodendrocytes myelination and long
      term spatial cognitive function in rats with perinatal hypoxia-ischemia (HI).
      Postnatal day 3 (P3) rats were subjected to right carotid artery ligation
      followed by 2.5 h of hypoxia (6% oxygen). Brain injury during the early and late
      phases was evaluated by immunostaining at P6 (72 h after the injury) and P47.
      Spatial cognitive function was evaluated at P42 using the Morris Water Maze test
      followed by histologic evaluation. HI caused an increase in pre-oligodendrocytes,
      astrocytes, and microglia in the ipsilateral white matter 72 h after the insult
      compared to contralateral regions and sham-operated controls (both p<0.05). There
      were significant decreases in myelin basic protein (MBP)and 2',3'-cyclic
      nucleotide 3'-phosphodiesterase (CNPase)-labeled oligodendrocytes with glial
      fibrillary acidic protein (GFAP)-labeled glial scarring in the ipsilateral
      periventricular white matter at P47 compared to contralateral regions and sham
      operated controls (all p<0.05). The rats with HI had spatial learning deficits in
      navigation trials (longer escape latency and swimming distance) and memory
      dysfunction in probe trials (fewer number of platform crossings and percentage of
      time in the target quadrant) compared with sham-operated controls (p<0.05). In
      this neonatal rat model of HI, myelination deficiency induced by activated
      astrocytes and microglia during the early phase with subsequent glial scarring
      was associated with long-term spatial learning and memory dysfunction.

PMID- 19747901
TI  - Association between myelin basic protein expression and left entorhinal cortex
      pre-alpha cell layer disorganization in schizophrenia.
AB  - There is evidence for migrational disturbances in the entorhinal cortex (ERC) in
      schizophrenia that supports a neurodevelopmental origin of the disorder. Since
      impaired myelin basic protein (MBP) gene expression during the migration phase
      could lead to abnormalities in final laminar position, we performed layer
      specific measurements of MBP expression in the ERC and hypothesised that
      migrational disturbances of pre-alpha-cell clusters relate to decreased MBP
      expression. Paraffin embedded sections of the left entorhinal cortex of 16
      schizophrenia patients and 10 control subjects were stained for MBP using routine
      immunohistochemistry. On each section representative regions of interest were
      scanned to attain optimal quality images of the gray matter. Results were
      correlated to previous published disturbed dispersion of pre-alpha-cell clusters
      in adjacent brain sections. Mean MBP stain-intensity was significantly reduced in
      schizophrenia patients. Absolute MBP stain-intensity was significantly reduced in
      layers III and IV in patients. A significant correlation of MBP stain-intensity
      with the distance of the deep pole of the pre-alpha-cell cluster from the gray
      white matter junction was observed in the ERC of schizophrenia patients. The
      present data provide evidence for reduced MBP expression in the ERC in
      schizophrenia, which implies deficits in axonal myelination and disturbed
      connectivity. MBP gene is expressed in oligodendrocytes and neuronal populations
      during embryonic development, which are important in establishing the structure
      of the cerebral cortex. Correlation between reduced MBP as a sign of down
      regulated MBP gene expression and disorganization of pre-alpha-cell clusters
      supports a neurodevelopmental origin of pathological processes in schizophrenia.

PMID- 19747900
TI  - Challenging the brain: Exploring the link between effort and cortical activation.
AB  - To better understand the contributions of effort on cortical activation
      associated with motor tasks, healthy participants with varying capacities for
      isolating the control of individual finger movements performed tasks consisting
      of a single concurrent abduction of all digits (Easy) and paired finger abduction
      with digits 2 and 3 abducted together concurrently with digits 4 and 5 (Hard).
      Brain activity was inferred from measurement using functional magnetic resonance
      imaging. Effort was measured physiologically using electrodermal responses (EDR)
      and subjectively using the Borg scale. On average, the Borg score for the Hard
      task was significantly higher (p=0.007) than for the Easy task (2.9+/-1.1 vs.
      1.4+/-0.7, respectively). Similarly, the average normalized peak-to-peak
      amplitude of the EDR was significantly higher (p=0.002) for the Hard task than
      for the Easy task (20.4+/-6.5% vs. 12.1+/-4.9%, respectively). The Hard task
      produced increases in sensorimotor network activation, including supplementary
      motor area, premotor, sensorimotor and parietal cortices, cerebellum and
      thalamus. When the imaging data were subdivided based on Borg score, there was an
      increase in activation and involvement of additional areas, including
      extrastriate and prefrontal cortices. Subdividing the data based on EDR amplitude
      produced greater effects including activation of the premotor and parietal
      cortices. These results show that the effort required for task performance
      influences the interpretation of fMRI data. This work establishes understanding
      and methodology for advancing future studies of the link between effort and motor
      control, and may be clinically relevant to sensorimotor recovery from neurologic
      injury.

PMID- 19747902
TI  - Effects of interleukin-15 on neuronal differentiation of neural stem cells.
AB  - Interleukin-15 (IL-15) signaling has pleiotropic actions in many cell types
      during development and has been best studied in cells of immune system lineage,
      where IL-15 stimulates proliferation of cytotoxic T cells and induces maturation
      of natural killer cells. A few reports have indicated that IL-15 and the IL-15
      receptor are expressed in central nervous system tissues and neuronal cell lines.
      Because this aspect of IL-15 action is poorly studied, we used cultured rat
      neural stem cells (NSCs) to study IL-15 signal transduction and activity. Primary
      cultures of rat NSCs in culture will form neurospheres and will differentiate
      into neuron, astrocyte, and oligodendrocyte progenitors under permissive
      conditions. We found by immunofluorescence that the IL-15Ralpha subunit of the IL
      15 receptor was expressed in NSCs and differentiating neurons, but not astrocyte
      or oligodendrocyte progenitors. We also showed that IL-15 treatment reduced MAP-2
      protein levels in neurons and could reduce neurite outgrowth in differentiating
      neurons but did not affect NSC proliferation, and cell proportions and viability
      of the corresponding lineage cells. In the presence of a STAT3 inhibitor,
      Stattic, IL-15 no longer reduced MAP-2 protein levels. IL-15 treatment caused
      STAT3 phosphorylation. Furthermore, using anti-IL-15Ralpha antibody to block IL
      15 signaling completely inhibited IL-15-induced phosphorylation of STAT3 and
      prevented IL-15 from decreasing neurite outgrowth. In conclusion, IL-15 may
      influence neural cell differentiation through a signal transduction pathway
      involving IL-15Ralpha and STAT3. This signal transduction modifies MAP-2 protein
      levels and, consequently, the differentiation of neurons from NSCs, as evidenced
      by reduced neurite outgrowth.

PMID- 19747903
TI  - Dystrophic dendrites in prefrontal cortical pyramidal cells of dopamine D1 and D2
      but not D4 receptor knockout mice.
AB  - Recent data indicate that cortical dopamine denervation results in dystrophic
      changes in the dendrites of pyramidal cells, including decreases in dendritic
      spine density and length. However, it is not known if the loss of signaling
      through specific dopamine receptors subserves these dendritic changes. We
      examined the dendritic structure of layer V pyramidal cells in the prefrontal
      cortex of D(1), D(2), and D(4) dopamine receptor null mutant mice and their wild
      type littermates. Decreased basal dendritic length and spine density were
      observed in the D(1) knockout mice. Similarly, a decrease in basal dendritic
      spine density was uncovered in the D(2) knockout mice relative to wild-type
      littermates. No changes in any dendritic parameter were observed in the D(4)
      knockout mice. These observations suggest that the dystrophic changes observed in
      prefrontal cortical pyramidal cell dendrites are due to loss of signaling through
      D(1) and possibly D(2) receptors. The current data also suggest that caution
      should be exercised in the interpretation of behavioral, physiological, and
      biochemical studies of the prefrontal cortex in dopamine receptor knockout mice.

PMID- 19747904
TI  - Development and validation of a sensitive liquid chromatography-tandem mass
      spectrometry assay to simultaneously measure androgens and estrogens in serum
      without derivatization.
AB  - BACKGROUND: Immunoassays are widely used to quantify steroid hormones in
      biological samples. However, they lack specificity, especially at low levels.
      This study aimed to develop a sensitive LC-MS/MS method to measure serum
      androgens and estrogens without derivatization within a single run. METHODS: A
      stable-isotope dilution LC-MS/MS method was established using atmospheric
      pressure photoionization to quantify testosterone (T), dihydrotestosterone (DHT),
      estradiol (E2) and estrone (E1) from serum. Sample preparation involved liquid
      liquid extraction (LLE) with hexane:ethyl acetate (3:2) containing deuterated
      internal standards. Accuracy was assessed by spiked recovery of serum pools, and
      imprecision by quality controls. RESULTS: Using 200 microL serum, limits of
      quantification were 0.3 pg (1.5 pg/mL) E(1), 0.5 pg (2.5 pg/mL) E(2), 2 pg (10
      pg/mL) T and 10 pg (50 pg/mL) DHT. Accuracy (93-110%) and precision (median 4%,
      all <15%) were determined to be well within acceptable limits for bioanalytical
      method validation. An analysis time of less than 10 min allowed up to 150 samples
      (600 analytes) to be processed per day. CONCLUSIONS: The method is sufficiently
      sensitive and precise to accurately quantify serum T levels in females and E(2)
      in males, and is readily adapted to tissue and non-human samples.

PMID- 19747905
TI  - A new standardized absolute quantitative RT-PCR method for detection of
      tyrosinase mRNAs in melanoma patients: technical and operative instructions.
AB  - BACKGROUND: To develop a new absolute quantitative real-time PCR method for blood
      mRNA tyrosinase assay and to compare this new method with standard RT-PCR nested.
      METHODS: Ten blood of melanoma patients (stages I-III), 5 tissue samples, 2
      surgical fresh metastatic skin and 3 lymph nodes paraffin-embedded slices were
      analysed, and 10 negative controls were used. Ten millilitres of blood was
      analysed for each individual. Three different protocols for RNA extraction and
      two reverse transcription methods were used. Specific human tyrosinase cDNA
      fragment was cloned into pcDNA3+ vector and then titrated for the standard curve
      construction (from 10(6) to 10(1)copies/microl). Recovery assays for RNA and
      cells were also performed. RESULTS: Our method was able to detect less than 5
      cells/10(8) WBC and about 100 fg of tyrosinase RNA. Very low CVs (<1.5%) were
      obtained on all samples run in triplicate. Sensitivity and specificity were of
      100%. The amount of starting volume of blood was crucial for the determination of
      copy number since large volumes are necessary for patient's monitoring.
      CONCLUSIONS: Our absolute qRT-PCR assay could be proposed as a new standardized
      molecular method for the management of melanoma patients, particularly for the
      follow up of the highest AJCC stages.

PMID- 19747906
TI  - The relationship between serum galectin-3 and serum markers of cardiac
      extracellular matrix turnover in heart failure patients.
AB  - BACKGROUND: A growing body of evidence links macrophage activation and fibrosis
      to the pathogenesis of heart failure (HF). Galectin-3 is one of the most likely
      mediators between macrophage activation and myocardial fibrosis. However, the
      exact relationship is unknown in humans. We assessed the impact of galectin-3 on
      serum markers of cardiac extracellular matrix (ECM) turnover in HF patients.
      METHODS: Patients with HF manifestations and a left ventricular ejection fraction
      (LVEF) <or=50% were enrolled in this study. Gender, age, medications, serum
      biochemical data, and outcomes of heart failure were recorded. Serum galectin-3,
      extracellular matrix including type I and III aminoterminal propeptide of
      procollagen (PINP and PIIINP), matrix metalloproteinase-2 (MMP-2), and tissue
      inhibitor of metalloproteinase-1 (TIMP-1) were analyzed. RESULTS: A total of 106
      (83 males and 23 females) patients were enrolled. The age was 61+/-16 y and LVEF
      was 35+/-9%. Their mean NYHA functional class was 2.2. Log galectin-3 was
      significantly correlated with log PIIINP (p=0.006), log TIMP-1 (p=0.025), log MMP
      2 (p=0.016), and NYHA functional class (p=0.034); but not age, sex or LVEF. After
      adjusting for age, sex, smoking status and LVEF, the relationship between
      galectin-3 and ECM turnover biomarkers (including PIIINP, TIMP, and MMP-2)
      remained significant. After adjusting for age, sex, smoking status and NYHA
      functional class, the relationship between galectin-3 and PIIINP or MMP-2
      remained significant. CONCLUSIONS: Galectin-3 is significantly correlated with
      serum markers of cardiac ECM turnover in HF patients. This implies a relationship
      between macrophage activation and ECM turnover in patients with HF.

PMID- 19747907
TI  - Chloral hydrate intoxication in a 3-month-old child: avoidance of hemodialysis by
      an immediate determination of trichloroethanol.
AB  - BACKGROUND: Chloral hydrate is used worldwide as a first-line agent for
      procedural sedation in paediatric patients undergoing painless diagnostic
      investigations. Chloral hydrate overdoses in children and adults have been
      reported to cause various toxicities, including central nervous system,
      respiratory and cardiac depression with sometimes fatal outcome. PATIENT AND
      METHODS: A 3-month-old girl was admitted after an unintentional administration of
      a 10-fold dose of chloral hydrate (667 mg/kg). She showed respiratory
      insufficiency in need of intubation and ventilation. Gastric endoscopy revealed
      esophagitis and gastric ulcerations. To assess the need for hemodialysis, serum
      trichloroethanol (TCE) was determined using a mass spectrometric quantification
      after a methyl tertiary butyl ether extraction using an external standard method.
      The serum TCE level 6 h after administration was 89 mg/L and declined to 20 mg/L
      within 24 h. The child could be extubated the next day; her further course was
      uneventful. CONCLUSION: The repeated determination of serum TCE levels prevented
      a technically difficult and risky hemodialysis in this very young patient.

PMID- 19747908
TI  - Development of novel microarray methodology for the study of mutations in the
      SERPINA1 and ADRB2 genes--their association with Obstructive Pulmonary Disease
      and Disseminated Bronchiectasis in Greek patients.
AB  - OBJECTIVES: The aim of our study was to determine the genetic risk conferred by
      SNPs in the SERPINA1 and ADRB2 for development of Chronic Obstructive Pulmonary
      Disease (COPD) and Disseminated Bronchiectasis (DB), while at the same time
      validating the NanoChip technology. This was a case-control study consisting of
      112 COPD, 62 DB patients and 2 control groups (106 smokers without COPD: healthy
      smokers control group and 205 general population subjects). DESIGN AND METHODS:
      The novel methodology of the Nanogen NanoChip(R) 400 (NC400 Nanogen
      www.nanogen.com) was employed for genotyping five mutations/SNPs in the SERPINA1
      and 2 in the ADRB2 gene. RESULTS: For the SERPINA1 gene a statistically
      significant difference in the frequency was found for heterozygotes for p.V213A
      between DB patients and healthy smokers (44.1% vs. 26.4% respectively; p=0.035)
      and for heterozygotes for c.1237G>A between DB patients and general population
      subjects (10.2% vs. 25.4% respectively; p=0.023). There was a clustering of ADRB2
      p.Gly16 homozygotes in patients with severe COPD (24/44, 54.5% with FEV(1) values
      <35% of predicted). CONCLUSIONS: The SERPINA1 p.V213A polymorphism was found
      associated with DB risk while the ADRB2 p.G16R is a risk factor for severe COPD
      in smokers.

PMID- 19747910
TI  - TGF-beta induces fibroblast activation protein expression; fibroblast activation
      protein expression increases the proliferation, adhesion, and migration of HO
      8910PM [corrected].
AB  - Several studies recognize cancer-stromal fibroblasts' role in cancer-cell
      invasion and metastasis. Through paracrine signaling molecules, TGF-beta and IL
      1beta, cancer cells activate stromal fibroblasts and induce the expression of
      fibroblast activation protein (FAP). FAP, in turn, affects the proliferation,
      invasion and migration of the cancer cells. We report that TGF-beta and IL-1beta
      are important factors in inducing differentiation of myofibroblasts and
      expression of functional markers, notably alpha-SMA. We discover that TGF-beta is
      the dominant factor in promoting FAPalpha protein expression. This study also
      examines FAP's function in vitro by assaying the proliferation, migration and
      invasion of ovarian cancer cell line HO-8910PM.

PMID- 19747909
TI  - Hemostatic properties of a venomic protein in rat organ trauma.
AB  - Previous in vitro work characterized the protease Q8009 isolated from the venom
      of the Australian brown snake Pseudonaja textilis textilis with Factor Xa-like
      activity and hemostatic properties. The purpose of the work described here
      characterizes the in vivo hemostatic properties in a rat model of parenchymatous
      organ injury. The key parameters of activity included reduction in time-to
      hemostasis and total volume of blood loss in spleen, liver and kidney wound
      models in rats. The surgical protocols involved exposure of the organs via a
      midline abdominal laparotomy. Using a clean metal template with 6, 6.5, 9 mm
      holes for spleen, liver and kidney, respectively, a predetermined volume of the
      organ was gently extruded through the template hole and excised with a razor
      blade. About 50 to 75 microL of collagen matrix with the different test solutions
      was applied to the wounds. Blood was collected and at the end of the procedure
      animals were humanely sacrificed with an anesthetic overdose. Determination of
      blood was performed using the hematin assay using a standard curve. Blood loss
      per minute and total blood loss were calculated. Results from the studies
      demonstrated that the application of Q8009 and collagen matrix to surgical wounds
      significantly reduced the total amount of blood loss and the time-to-hemostasis.
      In the spleen wound model, Q8009 at 100, 250 and 1000 microg/ml significantly
      reduced (p<0.001) the total volume of blood lost relative to thrombin and reduced
      the time-to-hemostasis by 25-50%, as compared to 7% by thrombin. In the liver
      wound model, Q8009 at 250 and 1000 microg/ml significantly reduced (p<0.001) the
      total volume of blood lost relative to thrombin and reduced the time-to
      hemostasis from 10.5 min by thrombin to 5.6 min with Q8009. In the kidney wound
      model, Q8009 at 250 microg/ml significantly reduced (p<0.05) the total volume of
      blood lost and reduced the time-to-hemostasis by 25% when compared to thrombin.
      The hemostasis levels were consistent with previous findings in skin wound rat
      models where Q8009 consistently reduced the total volume of blood lost and
      shortened time-to-hemostasis. Application of Q8009 plus collagen matrix
      significantly reduced the volume of total blood loss and time-to-hemostasis in
      rat surgical organ wound models induced bleeding, as compared to a commercially
      available hemostat device. The protein Q8009 has greater capacity to reduce blood
      loss and shorten time-to-hemostasis; highly desirable properties where rapid
      hemostasis is needed in surgical wounds in parenchymatous organs.

PMID- 19747911
TI  - Progenitor cell therapy for heart disease.
AB  - Many cell types are currently being studied as potential sources of
      cardiomyocytes for cell transplantation therapy to repair and regenerate damaged
      myocardium. The question remains as to which progenitor cell represents the best
      candidate. Bone marrow-derived cells and endothelial progenitor cells have been
      tested in clinical studies. These cells are safe, but their cardiogenic potential
      is controversial. The functional benefits observed are probably due to enhanced
      angiogenesis, reduced ventricular remodeling, or to cytokine-mediated effects
      that promote the survival of endogenous cells. Human embryonic stem cells
      represent an unlimited source of cardiomyocytes due to their great
      differentiation potential, but each step of differentiation must be tightly
      controlled due to the high risk of teratoma formation. These cells, however,
      confront ethical barriers and there is a risk of graft rejection. These last two
      problems can be avoided by using induced pluripotent stem cells (iPS), which can
      be autologously derived, but the high risk of teratoma formation remains. Cardiac
      progenitor cells have the advantage of being cardiac committed, but important
      questions remain unanswered, such as what is the best marker to identify and
      isolate these cells? To date the different markers used to identify adult cardiac
      progenitor cells also recognize progenitor cells that are outside the heart.
      Thus, it cannot be determined whether the cardiac progenitor cells identified in
      the adult heart represent resident cells present since fetal life or extracardiac
      cells that colonized the heart after cardiac injury. Developmental studies have
      identified markers of multipotent progenitors, but it is unknown whether these
      markers are specific for adult progenitors when expressed in the adult
      myocardium. Cardiac regeneration is dependent on the stability of the cells
      transplanted into the host myocardium and on the electromechanical coupling with
      the endogenous cells. Finally, the promotion of endogenous regenerative processes
      by mobilizing endogenous progenitors represents a complementary approach to cell
      transplantation therapy.

PMID- 19747912
TI  - Vav1 and PU.1 are recruited to the CD11b promoter in APL-derived promyelocytes:
      role of Vav1 in modulating PU.1-containing complexes during ATRA-induced
      differentiation.
AB  - Vav1 plays an important role in the all-trans retinoic acid (ATRA)-induced
      completion of the differentiation program of acute promyelocytic leukemia (APL)
      derived cells, in which it strengthens the drug effects and is involved in the
      regulation of maturation-related proteins, such as the CD11b surface antigen. In
      both myeloid and lymphoid cells, accumulating data attribute to the multidomain
      protein Vav1 a functional relevance in the control of gene expression, by direct
      interaction with chromatin remodeling and/or transcriptional proteins. The
      present study provides evidence that, in the APL-derived NB4 cell line, Vav1 and
      the transcription factor PU.1 cooperate in regulating the ATRA-induced CD11b
      expression. Both chromatin immunoprecipitation (ChIP) experiments and
      electrophoretic mobility shift assays (EMSA) indicate that Vav1 and PU.1 are
      recruited to CD11b promoter. Even if the two proteins may participate in diverse
      protein/DNA complexes, the amounts of complexes including PU.1 seem to be
      dependent on the interaction of this transcription factor with tyrosine
      phosphorylated Vav1. The reported data suggest that the ATRA-induced increase of
      Vav1 expression and tyrosine phosphorylation may be involved in recruiting PU.1
      to its consensus sequence on the CD11b promoter and, ultimately, in regulating
      CD11b expression during the late stages of neutrophil differentiation of APL
      derived promyelocytes.

PMID- 19747913
TI  - Neutrophil granulocytes promote the migratory activity of MDA-MB-468 human breast
      carcinoma cells via ICAM-1.
AB  - Tumor infiltrating neutrophil granulocytes do not only exhibit tumor eliminating
      functions but also promote tumor progression. We have recently shown that
      neutrophil granulocytes can serve as linking cells for the adhesion of MDA-MB-468
      breast carcinoma cells to pulmonary endothelium. Neutrophil granulocytes but not
      MDA-MB-468 cells express beta(2)-integrins, the ligands of the intercellular
      adhesion molecule (ICAM)-1, whereas ICAM-1 is strongly expressed on MDA-MB-468
      cells. Consequently, the herein presented study was performed to investigate if
      this interaction has also an influence on the migratory activity of the tumor
      cells and whether ICAM-1 signaling plays a role in this process, too. We found
      that the continuous release of interleukin-8 (IL-8) and GRO-alpha by MDA-MB-468
      cells increases the migratory activity of neutrophil granulocytes and attracts
      these cells towards the tumor cells which enables direct cell-cell interactions.
      These interactions in turn increase the migratory activity of the tumor cells in
      an ICAM-1 clustering-dependent mechanism since transfection of the tumor cells
      with specific siRNA against ICAM-1 abolished the effect. Moreover, ICAM-1 cross
      linking on tumor cells induces the phosphorylation of focal adhesion components
      such as focal adhesion kinase and paxillin via src kinase as well as the
      activation of the p38 MAPK pathway via Rho kinase in a time-dependent manner. Our
      results provide evidence that ICAM-1 is coupled to intracellular signaling
      pathways involved in tumor cell migration. Thus, neutrophil granulocytes can act
      as modulators of the metastatic capability of tumor cells by ligation of ICAM-1.

PMID- 19747914
TI  - Protein kinase C-delta mediates down-regulation of heterogeneous nuclear
      ribonucleoprotein K protein: involvement in apoptosis induction.
AB  - We reported previously that NSC606985, a camptothecin analogue, induces apoptosis
      of acute myeloid leukemia (AML) cells through proteolytic activation of protein
      kinase C delta (DeltaPKC-delta). By subcellular proteome analysis, heterogeneous
      nuclear ribonucleoprotein K (hnRNP K) was identified as being significantly down
      regulated in NSC606985-treated leukemic NB4 cells. HnRNP K, a docking protein for
      DNA, RNA, and transcriptional or translational molecules, is implicated in a host
      of processes involving the regulation of gene expression. However, the molecular
      mechanisms of hnRNP K reduction and its roles during apoptosis are still not
      understood. In the present study, we found that, following the appearance of the
      DeltaPKC-delta, hnRNP K protein was significantly down-regulated in NSC606985,
      doxorubicin, arsenic trioxide and ultraviolet-induced apoptosis. We further
      provided evidence that DeltaPKC-delta mediated the down-regulation of hnRNP K
      protein during apoptosis: PKC-delta inhibitor could rescue the reduction of hnRNP
      K; hnRNP K failed to be decreased in PKC-delta-deficient apoptotic KG1a cells;
      conditional induction of DeltaPKC-delta in U937T cells directly down-regulated
      hnRNP K protein. Moreover, the proteasome inhibitor also inhibited the down
      regulation of hnRNP K protein by apoptosis inducer and the conditional expression
      of DeltaPKC-delta. More intriguingly, the suppression of hnRNP K with siRNA
      transfection significantly induced apoptosis. To our knowledge, this is the first
      demonstration that proteolytically activated PKC-delta down-regulates hnRNP K
      protein in a proteasome-dependent manner, which plays an important role in
      apoptosis induction.

PMID- 19747915
TI  - The development of recurrent seizures after continuous intrahippocampal infusion
      of methionine sulfoximine in rats: a video-intracranial electroencephalographic
      study.
AB  - Glutamine synthetase is deficient in astrocytes in the epileptogenic hippocampus
      in human mesial temporal lobe epilepsy (MTLE). To explore the role of this
      deficiency in the pathophysiology of MTLE, rats were continuously infused with
      the glutamine synthetase inhibitor methionine sulfoximine (MSO, 0.625 microg/h)
      or 0.9% NaCl (saline control) unilaterally into the hippocampus. The seizures
      caused by MSO were assessed by video-intracranial electroencephalogram (EEG)
      monitoring. All (28 of 28) of the MSO-treated animals and none (0 of 12) of the
      saline-treated animals developed recurrent seizures. Most recurrent seizures
      appeared in clusters of 2 days' duration (median; range, 1 to 12 days). The first
      cluster was characterized by frequent, predominantly stage I seizures, which
      presented after the first 9.5 h of infusion (median; range, 5.5 to 31.7 h).
      Subsequent clusters of less-frequent, mainly partial seizures occurred after a
      clinically silent interval of 7.1 days (median; range, 1.8 to 16.2 days). The
      ictal intracranial EEGs shared several characteristics with recordings of partial
      seizures in humans, such as a distinct evolution of the amplitude and frequency
      of the EEG signal. The neuropathology caused by MSO had similarities to
      hippocampal sclerosis in 23.1% of cases, whereas 26.9% of the animals had minimal
      neuronal loss in the hippocampus. Moderate to severe diffuse neuronal loss was
      observed in 50% of the animals. In conclusion, the model of intrahippocampal MSO
      infusion replicates key features of human MTLE and may represent a useful tool
      for further studies of the cellular, molecular and electrophysiological
      mechanisms of this disorder.

PMID- 19747916
TI  - The little-known Dipteropeltis hirundo Calman, 1912 (Crustacea, Branchiura): SEM
      investigations of paratype material in light of recent phylogenetic analyses.
AB  - The Branchiura are fish ectoparasites which include the well-known and very
      commonly found genus Argulus. But the Branchiura also contains the monotypic
      genus Dipteropeltis, about which only very little is known. In this investigation
      of two female paratype specimens we describe for the first time the external
      morphology of Dipteropeltis based on Scanning Electron Microscopy. We show that
      Dipteropeltis has a pre-oral spine, unique suction disc support structures, an
      Argulus-like mouth cone and second maxillae with a combination of features seen
      in both Argulus and Chonopeltis. These data are compared with data from the three
      remaining branchiuran genera Dolops, Chonopeltis and Argulus and discussed in a
      phylogenetic context based on a recently proposed phylogeny of the group.

PMID- 19747917
TI  - Natural killer cells are polarized toward cytotoxicity in chronic hepatitis C in
      an interferon-alfa-dependent manner.
AB  - BACKGROUND & AIMS: Patients with chronic hepatitis C virus (HCV) infection
      display great variability in disease activity and progression. Although virus
      specific adaptive immune responses have been characterized extensively and found
      to be impaired in chronic hepatitis C, the role of innate immune responses in
      disease activity and progression of chronic hepatitis C is not well understood.
      METHODS: We studied 42 HCV-infected patients and 12 healthy uninfected controls.
      RESULTS: We found an increased frequency of natural killer (NK) cells expressing
      tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), NKp44, NKG2C,
      and CD122 in chronic hepatitis C as compared with healthy controls (P < .05 for
      all markers) and stronger activation of NK cells in the liver than in the blood
      (P < .05). This NK cell phenotype was associated with polarization of NK cell
      function toward CD107a expression as a marker of degranulation, but with not
      increased interferon (IFN)-gamma production of CD56(dim) NK cells. The polarized
      NK cell phenotype correlated with alanine aminotransferase levels (r(2) = 0.312,
      P = .03). To investigate whether in vivo exposure of NK cells to HCV-induced type
      I IFN was causing this NK cell phenotype, peripheral blood mononuclear cells from
      10 healthy controls and 8 HCV-infected patients were stimulated in the presence
      of IFN-alfa, which resulted in increased NK cell expression of TRAIL and CD107a
      (P < .001), but not IFN-gamma. CONCLUSIONS: Collectively, these results describe
      a polarized NK cell phenotype induced by chronic exposure to HCV-induced IFN
      alfa. This phenotype may contribute to liver injury through TRAIL expression and
      cytotoxicity, whereas the lacking increase in IFN-gamma production may facilitate
      the inability to clear HCV.

PMID- 19747918
TI  - Effect of HCV RNA suppression during peginterferon alfa-2a maintenance therapy on
      clinical outcomes in the HALT-C trial.
AB  - BACKGROUND & AIMS: The Hepatitis C Antiviral Long-term Treatment Against
      Cirrhosis (HALT-C) trial demonstrated that low-dose peginterferon maintenance
      therapy was ineffective in preventing clinical outcomes in patients with chronic
      hepatitis C, advanced fibrosis, and failure to achieve a sustained virologic
      response during lead-in phase treatment with standard dose
      peginterferon/ribavirin. This analysis was performed to determine whether
      suppressing HCV RNA during the trial was associated with a reduction in clinical
      outcomes. METHODS: Seven hundred sixty-four patients treated during the lead-in
      phase of HALT-C trial were randomized to either peginterferon alfa-2a (90
      microg/week) maintenance therapy or no treatment (control) for 3.5 years.
      Clinical outcomes included an increase in Child-Turcotte-Pugh score, ascites,
      spontaneous bacterial peritonitis, hepatic encephalopathy, variceal hemorrhage,
      hepatocellular carcinoma, and mortality. RESULTS: During the lead-in, >or=4
      log(10) decline in serum HCV RNA occurred in 178 patients; 82% of whom lost
      detectable HCV RNA and later broke through or relapsed. These patients had
      significantly (P = .003) fewer clinical outcomes whether randomized to
      maintenance therapy or control. Following randomization, serum HCV RNA increased
      significantly in all 90 control patients and in 58 of 88 receiving maintenance
      therapy. Only 30 patients had persistent suppression of HCV RNA by >or=4 log(10)
      during maintenance therapy. No significant reduction in clinical outcomes was
      observed in these patients. CONCLUSIONS: Viral suppression by >or=4 log(10) with
      full-dose peginterferon/ribavirin is associated with a significant reduction in
      clinical outcomes. Continuing low-dose peginterferon maintenance therapy, even in
      patients with persistent viral suppression, does not lead to a further decline in
      clinical outcomes.

PMID- 19747919
TI  - Retinoic acid receptor antagonists inhibit miR-10a expression and block
      metastatic behavior of pancreatic cancer.
AB  - BACKGROUND & AIMS: The infiltrating ductal adenocarcinoma of the pancreas is
      among the most lethal of all solid malignancies, largely owing to a high
      frequency of early metastasis. We identified microRNA-10a (miR-10a) as an
      important mediator of metastasis formation in pancreatic tumor cells and
      investigated the upstream and downstream regulatory mechanisms of miR-10a.
      METHODS: Northern blot analysis revealed increased expression levels of miR-10a
      in metastatic pancreatic adenocarcinoma. The role of miR-10a was analyzed by
      Morpholino and short interfering RNA transfection of pancreatic carcinoma cell
      lines and resected specimens of human pancreatic carcinoma. Metastatic behavior
      of primary pancreatic tumors and cancer cell lines was tested in
      xenotransplantation experiments in zebrafish embryos. RESULTS: We show that miR
      10a expression promotes metastatic behavior of pancreatic tumor cells and that
      repression of miR-10a is sufficient to inhibit invasion and metastasis formation.
      We further show that miR-10a is a retinoid acid target and that retinoic acid
      receptor antagonists effectively repress miR-10a expression and completely block
      metastasis. This antimetastatic activity can be prevented by specific knockdown
      of HOX genes, HOXB1 and HOXB3. Interestingly, suppression of HOXB1 and HOXB3 in
      pancreatic cancer cells is sufficient to promote metastasis formation.
      CONCLUSIONS: These findings suggest that miR-10a is a key mediator of metastatic
      behavior in pancreatic cancer, which regulates metastasis via suppression of
      HOXB1 and HOXB3. Inhibition of miR-10a expression (with retinoic acid receptor
      antagonists) or function (with specific inhibitors) is a promising starting point
      for antimetastatic therapies.

PMID- 19747921
TI  - Biochemical and pathogenic properties of the natural isolate of Shewanella algae
      from Peter the great bay, sea of Japan.
AB  - Pathogenic properties of the natural isolate of Shewanella algae from the
      coelomic fluid of the sea cucumber Apostichopus japonicus (Peter the Great Bay,
      Sea of Japan) were investigated. The isolate had oxydative metabolism, was
      positive for ornithine decarboxylase, cytochrome oxidase, catalase, DNase and
      gelatinase, hemolytically active, did not produce acid from carbohydrates, and
      did not hydrolyze urea and esculin. The strain was resistant to penicillin,
      amoxicillin, and ampicillin and susceptible to tetracycline and carbenicillin.
      Among cellular fatty acids, 13:0-i, 15:0-i, 16:0, 16:1(n-7), 17:0-i, and 17:0-ai
      dominated. These biochemical properties made it possible to attribute the
      isolated bacteria to the genus Shewanella and identified as S. algae. The cells
      of this bacterium were introduced into the coelomic cavity of another echinoderm,
      the sea urchin Strongylocentrotus nudus. As a result, in about 24h the animals
      became slow and 3-8days after the inoculation died. Dividing bacteria were being
      found during the experiment in the coelomic fluid as well as in the phagosomes of
      amoebocytes, i.e. cells acting as phagocytes in the coelomic fluid. The studies
      of the invasive properties of strain 156 showed that bacterial cells entered the
      subcuticular space of S. nudus and A. japonicus through the cuticle and stayed
      there for a long time without penetrating epithelium and exerting toxic effect
      upon the organisms of the laboratory animals. Pathogenic effect of S. algae can
      be manifested only if the cutaneous epithelium is destroyed permitting it to
      penetrate the lower tissue layers. The toxicity of S. algae is confirmed by in
      vitro experiments. The inoculation of the embryonic cells of S. nudus with
      samples of this bacterium caused the death of 10% of cells within an hour and
      100% of cells within 12h after inoculation. The results of the investigations
      demonstrate that S. algae could produce opportunistic infection in the sea
      cucumber A. japonicus and the sea urchin S. nudus, which may be natural
      reservoirs of this human pathogen.

PMID- 19747920
TI  - Enteropathogenic Escherichia coli infection inhibits intestinal serotonin
      transporter function and expression.
AB  - BACKGROUND & AIMS: Serotonin transporter (SERT) plays a critical role in
      regulating serotonin (5-hydroxytryptamine [5-HT]) availability in the gut.
      Elevated 5-HT levels are associated with diarrheal conditions such as irritable
      bowel syndrome and enteric infections. Whether alteration in SERT activity
      contributes to the pathophysiology of diarrhea induced by the food-borne pathogen
      enteropathogenic Escherichia coli (EPEC) is not known. The present studies
      examined the effects of EPEC infection on SERT activity and expression in
      intestinal epithelial cells and elucidated the underlying mechanisms. METHODS:
      Caco-2 cells as a model of human intestinal epithelia and EPEC-infected C57BL/6J
      mouse model of infection were utilized. SERT activity was measured as Na(+) and
      Cl(-) dependent (3)[H] 5-HT uptake. SERT expression was measured by real-time
      quantitative reverse-transcription polymerase chain reaction, Western blotting,
      and immunofluorescence studies. RESULTS: Infection of Caco-2 cells with EPEC for
      30-120 minutes decreased apical SERT activity (P < .001) in a type 3 secretion
      system dependent manner and via involvement of protein tyrosine phosphatases.
      EPEC infection decreased V(max) of the transporter; whereas cell surface
      biotinylation studies revealed no alteration in the cellular or plasma membrane
      content of SERT in Caco-2 cells. EPEC infection of mice (24 hours) reduced SERT
      immunostaining with a corresponding decrease in SERT messenger RNA levels, 5-HT
      uptake, and mucosal 5-HT content in the small intestine. CONCLUSIONS: Our results
      demonstrate inhibition of SERT by EPEC and define the mechanisms underlying these
      effects. These data may aid in the development of a novel pharmacotherapy to
      modulate the serotonergic system in treatment of infectious diarrheal diseases.

PMID- 19747922
TI  - Kinetic advantage of intrinsically disordered proteins in coupled folding-binding
      process: a critical assessment of the "fly-casting" mechanism.
AB  - Intrinsically disordered proteins (IDPs) are recognized to play important roles
      in many biological functions such as transcription and translation regulation,
      cellular signal transduction, protein phosphorylation, and molecular assemblies.
      The coupling of folding with binding through a "fly-casting" mechanism has been
      proposed to account for the fast binding kinetics of IDPs. In this article,
      experimental data from the literature were collated to verify the kinetic
      advantages of IDPs, while molecular simulations were performed to clarify the
      origin of the kinetic advantages. The phosphorylated KID-kinase-inducible domain
      interacting domain (KIX) complex was used as an example in the simulations. By
      modifying a coarse-grained model with a native-centric Go-like potential, we were
      able to continuously tune the degree of disorder of the phosphorylated KID domain
      and thus investigate the intrinsic role of chain flexibility in binding kinetics.
      The simulations show that the "fly-casting" effect is not only due to the greater
      capture radii of IDPs. The coupling of folding with binding of IDPs leads to a
      significant reduction in binding free-energy barrier. Such a reduction
      accelerates the binding process. Although the greater capture radius has been
      regarded as the main factor in promoting the binding rate of IDPs, we found that
      this parameter will also lead to the slower translational diffusion of IDPs when
      compared with ordered proteins. As a result, the capture rate of IDPs was found
      to be slower than that of ordered proteins. The main origin of the faster binding
      for IDPs are the fewer encounter times required before the formation of the final
      binding complex. The roles of the interchain native contacts fraction (Q(b)) and
      the mass-center distance (DeltaR) as reaction coordinates are also discussed.

PMID- 19747923
TI  - Cancer-associated mutations in BRC domains of BRCA2 affect homologous
      recombination induced by Rad51.
AB  - The tumor suppressor BRCA2 protein plays a major role in the regulation of Rad51
      catalyzed homologous recombination. BRCA2 interacts with monomeric Rad51
      primarily via conserved BRC domains and coordinates the formation of Rad51
      filaments at double-stranded DNA (dsDNA) breaks. A number of cancer-associated
      mutations in BRC4 and BRC2 domains have been reported. To elucidate their effects
      on homologous recombination, we studied Rad51 filament formation on single
      stranded DNA and dsDNA substrates and Rad51-catalyzed strand exchange, in the
      presence of wild-type and mutated peptides of either BRC4 or BRC2. While the wild
      type BRC2 and BRC4 peptides inhibited filament formation and, thus, strand
      exchange, the mutated forms decreased significantly these inhibitory effects.
      These results are consistent with a three-dimensional model for the interface
      between individual BRC repeats and Rad51. We suggest that mutations at sites
      crucial for the association between Rad51 and BRC domains impair the ability of
      BRCA2 to recruit Rad51 to dsDNA breaks, hampering recombinational repair.

PMID- 19747924
TI  - A network-based approach for resistance transmission in bacterial populations.
AB  - Horizontal transfer of mobile genetic elements (conjugation) is an important
      mechanism whereby resistance is spread through bacterial populations. The aim of
      our work is to develop a mathematical model that quantitatively describes this
      process, and to use this model to optimize antimicrobial dosage regimens to
      minimize resistance development. The bacterial population is conceptualized as a
      compartmental mathematical model to describe changes in susceptible, resistant,
      and transconjugant bacteria over time. This model is combined with a
      compartmental pharmacokinetic model to explore the effect of different plasma
      drug concentration profiles. An agent-based simulation tool is used to account
      for resistance transfer occurring when two bacteria are adjacent or in close
      proximity. In addition, a non-linear programming optimal control problem is
      introduced to minimize bacterial populations as well as the drug dose. Simulation
      and optimization results suggest that the rapid death of susceptible individuals
      in the population is pivotal in minimizing the number of transconjugants in a
      population. This supports the use of potent antimicrobials that rapidly kill
      susceptible individuals and development of dosage regimens that maintain
      effective antimicrobial drug concentrations for as long as needed to kill off the
      susceptible population. Suggestions are made for experiments to test the
      hypotheses generated by these simulations.

PMID- 19747925
TI  - Background evolution in camouflage systems: a predator-prey/pollinator-flower
      game.
AB  - A common predator or anti-predator strategy involves camouflage based on
      background matching. In some systems, the background is an organism whose fitness
      is affected by the predator-prey interaction. In these cases, the phenotype of
      the background species may evolve to affect the degree of background matching in
      the predator-prey interaction. For example, some flower species (the background)
      are inhabited by camouflaged ambush predators that attack visiting pollinators.
      These flowers have a fitness interest in the outcome of the predator-prey
      interaction because flowers depend on pollinator visitations for reproduction.
      Therefore, floral colour might evolve relative to predator colour so as to
      influence the detectability of resident predators. I have created a three-player
      game, based on Signal Detection Theory, to model the co-evolution of predator and
      prey/pollinator behavioural strategies with floral colour. This model makes two
      general predictions: (1) Constraints on predator distributions favour the
      evolution of flowers that match the predators' colour because they prevent
      predators from overexploiting these flowers; (2) factors that produce less
      discriminating pollinators also favour the evolution of flowers that match the
      predators' colour because these pollinators are willing to land on these flowers
      even if the safety of the flower is in doubt.

PMID- 19747926
TI  - PKCalpha-MAPK/ERK-phospholipase A2 signaling is required for human melanoma
      enhanced brain endothelial cell proliferation and motility.
AB  - The largely undefined signal transduction mechanisms and cross-talk between human
      melanoma cell (HMC) lines and brain endothelial cells (ECs) involved in tumor
      cell interaction and adhesion were investigated. In immortalized rat brain GP8.3
      EC cultures, conditioned media (CM) prepared from SK-MEL28 and OCM-1 melanoma
      cells significantly enhanced arachidonic acid release, cytosolic phospholipase
      A(2) (cPLA(2)) and Ca(+)-independent phospholipase A(2) (iPLA(2)) specific
      activities, and cell growth by 24 h. Inhibitors such as wortmannin and LY294002
      (vs. PI3 kinase activity), AACOCF(3), (vs. cPLA(2) and iPLA(2)), PD98059 (vs.
      ERK1/2 activity) and NS-398 (vs. cyclooxygenase-2 activity, COX-2) were all able
      to block cell proliferation and motility determined using a scratch wound healing
      assay in melanoma CMs-stimulated EC monolayers. These media also support the
      enhanced cell proliferation of primary ECs derived from rat brain (BBEC).
      Electroporation of anti-cPLA(2) antibody into ECs markedly inhibited the EC
      proliferation in response to CMs. With both CMs, phosphorylation of cPLA(2),
      PKCalpha, ERK1/2, protein and mRNA expression of cPLA(2) and iPLA(2), and COX-2
      protein expression were significantly stimulated after 24 h coincubation, and
      attenuated by specific inhibitors. By confocal microscopy, activation of cPLA(2),
      ERK1/2, PKCalpha and COX-2 in perinuclear and membrane regions of ECs grown in CM
      stimulated cultures were clearly observed. Thus MEK-PKCalpha-ERK1/2 and PI3-K/Akt
      survival pathways are activated in EC cultures during the interaction with CM
      from both melanoma cell lines, providing new insight in understanding EC
      metabolism and signaling. These pathways represent potential therapeutic targets
      to inhibit or enhance tumor angiogenesis.

PMID- 19747927
TI  - Serotonin 1A receptor gene is associated with Japanese methamphetamine-induced
      psychosis patients.
AB  - BACKGROUND: Several investigations have reported associations the serotonin 1A (5
      HT1A) receptor to schizophrenia and psychotic disorders, making 5-HT1A receptor
      gene (HTR1A) an adequate candidate gene for the pathophysiology of schizophrenia
      and methamphetamine (METH)-induced psychosis. Huang and colleagues reported that
      rs6295 in HTR1A was associated with schizophrenia. The symptoms of
      methamphetamine (METH)-induced psychosis are similar to those of paranoid type
      schizophrenia. It may indicate that METH-induced psychosis and schizophrenia have
      common susceptibility genes. In support of this hypothesis, we reported that the
      V-act murine thymoma viral oncogene homologue 1 (AKT1) gene was associated with
      METH-induced psychosis and schizophrenia in the Japanese population. Furthermore,
      we conducted an analysis of the association of HTR1A with METH-induced psychosis.
      METHOD: Using one functional SNP (rs6295) and one tagging SNP (rs878567), we
      conducted a genetic association analysis of case-control samples (197 METH
      induced psychosis patients and 337 controls) in the Japanese population. The age
      and sex of the control subjects did not differ from those of the methamphetamine
      dependence patients. RESULTS: Rs878567 was associated with METH-induced psychosis
      patients in the allele/genotype-wise analysis. Moreover, this significance
      remained after Bonferroni correction. In addition, we detected an association
      between rs6295 and rs878567 in HTR1A and METH-induced psychosis patients in the
      haplotype-wise analysis. Although we detected an association between rs6295 and
      METH-induced psychosis patients, this significance disappeared after Bonferroni
      correction. CONCLUSION: HTR1A may play an important role in the pathophysiology
      of METH-induced psychosis in the Japanese population. However, because we did not
      perform a mutation scan of HTR1A, a replication study using a larger sample may
      be required for conclusive results.

PMID- 19747928
TI  - Atrophy in two attention networks is associated with performance on a Flanker
      task in neurodegenerative disease.
AB  - This study investigated the neurobiological basis of attentional control
      dysfunction in neurodegenerative disease by determining the effect of regional
      brain atrophy on Flanker task performance of neurodegenerative patients. We
      hypothesized that atrophy in DLPFC and ACC would be significantly associated with
      decreased attentional control performance on the Flanker task. We used voxel
      based morphometry (VBM) to measure the relationship between MRI measures of
      regional grey matter atrophy and performance on a version of the Flanker task,
      measured by accuracy and response time. Sixty-five subjects participated,
      including patients with frontotemporal dementia, Alzheimer's disease, mild
      cognitive impairment, non-fluent progressive aphasia, corticobasal degeneration,
      progressive supranuclear palsy, semantic dementia, and healthy controls. Accuracy
      measures of attentional control and response time measures of attentional control
      were associated with two different patterns of regional atrophy across subjects.
      First, there was an association between left hemisphere DLPFC and ACC atrophy and
      poorer attentional control accuracy. Second, right hemisphere temporal-parietal
      junction (TPJ) and ventrolateral prefrontal cortex (VLPFC) and DLPFC atrophy were
      associated with slower response times during attentional control on accurate
      trials, which may reflect emergent involvement due to deficits in the DLPFC-ACC
      network.

PMID- 19747929
TI  - Traumatic brain injury affects the frontomedian cortex--an event-related fMRI
      study on evaluative judgments.
AB  - Traumatic brain injuries represent the leading cause of death and disability in
      young adults in industrialized countries. Recently, it has been suggested that
      dysfunctions of the frontomedian cortex, which enables social cognition, are
      responsible for clinical deficits in the long-term. To validate this hypothesis,
      we examined brain activation in seven young adults suffering from diffuse axonal
      injury during a cognitive task that specifically depends on frontomedian
      structures, namely evaluative judgments, contrasted with semantic memory
      retrieval. Brain activation in patients was compared with healthy age and gender
      matched control subjects using event-related functional magnetic resonance
      imaging. Evaluative judgments were related to a neural network discussed in the
      context of self-referential processing and theory of mind. More precisely, the
      neural network consisted of frontomedian regions, the temporal pole, and the
      posterior superior temporal gyrus and sulcus/angular gyrus. Patients showed
      higher activations in this network and the inferior frontal gyrus, whereas
      healthy control subjects activated more dopaminergic structures, namely the
      ventral tegmental area, during evaluative judgments. One possible interpretation
      of the data is that deficits in the ventral tegmental area, and consequently the
      mesocorticolimbic projection system, have to be compensated for by higher brain
      activations in the frontomedian and anterior cingulate cortex in patients with
      diffuse axonal injury. In conclusion, our study supports the hypothesis that
      traumatic brain injury is characterized by frontomedian dysfunctions, which may
      be responsible for clinical deficits in the long-term and which might be modified
      by rehabilitative strategies in the future.

PMID- 19747930
TI  - The effect of intranasal administration of oxytocin on fear recognition.
AB  - The oxytocinergic system has recently been placed amongst the most promising
      targets for various psychiatric treatments due to its role in prosocial behavior
      and anxiety reduction. Although recent studies have demonstrated a general effect
      of administration of oxytocin on emotion recognition, no study to date has
      examine the effect of oxytocin on each emotion separately. In the present study,
      a double-blind placebo-controlled crossover design was used in a dynamic facial
      expression task, in order to assess the effects of administration of oxytocin on
      emotion recognition. A single dose of oxytocin or a placebo was administered
      intranasally to 27 healthy male subjects 45 min prior to task performance. The
      results showed that a single intranasal administration of oxytocin, as opposed to
      the placebo, improved the subjects' ability to recognize fear, but not other
      emotions. These results suggest a specific role for oxytocin in fear recognition,
      which could be relevant for clinical disorders that manifest deficits in
      processing emotional facial expressions, particularly fear.

PMID- 19747931
TI  - Equilibrium mechanisms of receptor clustering.
AB  - Receptor clustering is a well-established feature of transmembrane signalling. In
      some cellular systems, clusters form dynamically in response to activation by an
      extracellular ligand; in others, extensive 2-dimensional arrays of receptors
      persist for long periods of time on the cell surface. Compelling evidence has
      accumulated that the interactions between receptors within a cluster play an
      important role in the signalling process. Here, we review statistical mechanical
      models that describe how clusters may be generated and maintained by the
      equilibrium thermodynamic interactions between receptors, the extracellular
      ligands that bind to their periplasmic domains, and cytosolic 'adaptor proteins'
      that bind to the cytoplasmic domains of the receptors. We discuss how adaptor
      proteins might permit cells to exert control over the propensity of cluster
      formation, and to target clusters to specific locations on the cell surface. We
      further outline how differential interactions between active and inactive
      receptors can enhance the sensitivity of the cellular response through the
      mechanism of 'conformational spread'.

PMID- 19747932
TI  - Quinine, a selective gap junction blocker, decreases REM sleep in rats.
AB  - Electrical synapses are formed by gap junctions that allow the direct
      communication between neurons, the intercellular transference of ions and small
      molecules as well as the electrical coupling of the cells. Electrical coupling in
      neurons is mediated by the gap junction protein connexin36. There are reports
      about the presence of electrical coupling in the sublaterodorsal nucleus and
      pedunculopontine nucleus, which have been implicated in the modulation of the
      rapid eye movement sleep. In the present study, rats were used to examine the
      possible changes on the sleep-wake states after intracerebroventricular
      administration of several doses of quinine, a selective blocker of gap junctions
      formed by connexin36. The results showed that quinine significantly increased the
      time spent in wakefulness and decreased the time spent in slow wave sleep along
      the 24h of polygraphic recording. The three doses used of quinine caused a
      significant decrease of rapid eye movement sleep along the light phase; however,
      only one dose extended such effect until the darkness phase. The changes on sleep
      wake states of the rat after the blockage of gap junctions formed by connexin36
      suggest that electrical synapses could contribute to the regulation of sleep-wake
      states in concert with the well-known chemical neurotransmission.

PMID- 19747933
TI  - Effect of kappa-opioid receptor agonists U69593, U50488H, spiradoline and
      salvinorin A on cocaine-induced drug-seeking in rats.
AB  - Our previous work indicated that pretreatment with the selective kappa-opioid
      receptor (KOPr) agonist, U69593, attenuated the ability of priming injections of
      cocaine to reinstate extinguished cocaine-seeking behavior. The present study
      expanded these initial tests to include other traditional KOPr agonists, U50488H,
      spiradoline (SPR), and salvinorin A (Sal A), an active constituent of the plant
      Salvia divinorum. Following acquisition and stabilization of cocaine self
      administration, cocaine-produced drug-seeking was measured. This test was
      conducted in a single day and comprised an initial phase of self-administration,
      followed by a phase of extinguished responding. The final phase examined
      reinstatement of extinguished cocaine self-administration followed by a priming
      injection of cocaine (20.0mg/kg, intraperitoneal (I.P.)) in combination with the
      various KOPr agonists. Cocaine-induced drug-seeking was attenuated by
      pretreatment with U69593 (0.3mg/kg, subcutaneous (S.C.)), U50488H (30.0mg/kg,
      I.P.), SPR (1.0, 3.0mg/kg, I.P.) and Sal A (0.3, 1.0mg/kg, I.P.). Sal A (0.3,
      1.0mg/kg, I.P.) had no effect on operant responding to obtain sucrose
      reinforcement or on cocaine-induced hyperactivity. These findings show that Sal
      A, like other traditional KOPr agonists attenuates cocaine-induced drug-seeking
      behavior.

PMID- 19747934
TI  - A selective ALDH-2 inhibitor reduces anxiety in rats.
AB  - CVT-10216 is a highly selective, reversible inhibitor of ALDH-2 that reduces
      excessive alcohol drinking. Anxiety plays a role in alcoholism. The present study
      asks whether CVT-10216 has anxiolytic properties, as reflected in social
      interaction behavior in four unrelated rodent models: endogenous anxiety-like
      behavior in naive Fawn-Hooded rats, repeated alcohol-withdrawal-induced anxiety,
      restraint stress-induced anxiety and drug-induced anxiety. CVT-10216 counteracted
      anxiety in all models except that produced by the 5-HT(2C) agonist, mCPP. CVT
      10216 exhibited both acute and prophylactic inhibitions of repeated alcohol
      withdrawal-induced anxiety. Importantly, anxiogenic behavior induced by the
      benzodiazepine receptor inverse agonist, DMCM, was counteracted dose-dependently
      by CVT-10216. Thus, a non-addictive selective inhibitor of ALDH-2 has both
      anxiolytic and antidipsotropic properties, which may be dependent, in part on the
      involvement of the GABA-benzodiazepine system.

PMID- 19747935
TI  - Systemic administration of doxorubicin impairs aversively motivated memory in
      rats.
AB  - There is growing clinical evidence of cognitive impairment in cancer patients
      treated with chemotherapy, especially in women treated with drug combinations for
      breast cancer. Clinical studies have a difficult task of defining which drugs
      individually are responsible for the cognitive changes and published papers
      evaluating single agents in experimental models are scanty. In the present study
      we have investigated the effect of single escalating doses of doxorubicin (DOX)
      on memory for inhibitory avoidance conditioning (IA) in rats. The doses used were
      comparable to those applied in the clinic. When given systemically before
      training, higher doses of DOX impaired IA memory retention measured 24h and
      7days, but not 3h after training. DOX did not affect IA retention when given
      either before or after training in a multiple-trial IA training protocol. Control
      experiments showed that DOX produced a decrease in exploratory behavior assessed
      by the number of rearings performed during exploration of an open field. The
      results indicate that a single systemic administration of DOX might impair long
      term aversive learning.

PMID- 19747936
TI  - Economic evaluation of skin cancer prevention in Australia.
AB  - OBJECTIVES: Australia has the highest incidence of skin cancer in the world,
      despite prevention campaigns being implemented since the early 1980s. This study
      assesses the cost-effectiveness of a skin cancer prevention program (named
      SunSmart) since it was introduced, together with its potential cost-effectiveness
      as an upgraded and ongoing national program. METHODS: The reduction in melanoma
      incidence attributable to SunSmart was modelled as the primary end-point.
      Historical expenditures on SunSmart were obtained from representative Australian
      states in three latitude zones. Melanoma incidence rates from these states were
      used to model key health outcomes. Non-melanoma skin cancer was modelled
      separately based on national survey results. RESULTS: We estimate that SunSmart
      has averted 28,000 disability-adjusted life-years (DALYs), equivalent to 22,000
      life-years saved, in the state of Victoria since its introduction in 1988, as
      well as saving money from cost offset in skin cancer management (dominant). An
      upgraded national program for the next 20 years is estimated to avert 120,000
      DALYs, with associated reductions in the use of health care resources. It remains
      a dominant intervention in which every dollar invested in SunSmart will return an
      estimated AU$2.30. CONCLUSIONS: This study demonstrates that a sustained modest
      investment in skin cancer control is likely to be an excellent value for money.

PMID- 19747937
TI  - Cost-effectiveness of a behavioral weight loss intervention for low-income women:
      the Weight-Wise Program.
AB  - OBJECTIVE: Assess the cost-effectiveness of a 16-week weight loss intervention
      (Weight-Wise) for low-income midlife women. METHOD: A randomized controlled trial
      conducted in North Carolina in 2007 tested a weight loss intervention among 143
      women (40-64 years old, mean BMI=35.1 kg/m(2)). Women were randomized to one of
      two arms-special intervention (n=72) and a wait-listed control group (n=71).
      Effectiveness measures included changes in weight, systolic and diastolic blood
      pressure, total cholesterol, and HDL cholesterol. Cost-effectiveness measures
      calculated life years gained (LYG) from changes in weight, based on excess years
      life lost (YLL) algorithm. RESULTS: Intervention participants had statistically
      significant decreases in weight (kg) (-4.4 95% CI=-5.6, -3.2) and in systolic
      blood pressure (-6.2 mm Hg, 95% CI=-10.6, -1.7) compared to controls. Total cost
      of conducting Weight-Wise was $17,403, and the cost per participant in
      intervention group was $242. The incremental cost per life year gained
      (discounted) from a decrease in obesity was $1862. CONCLUSION: Our results
      suggest the Weight-Wise intervention may be a cost-effective approach to
      improving the health of low-income women.

PMID- 19747938
TI  - Physical activity of children and youth in Nova Scotia from 2001/02 and 2005/06.
AB  - OBJECTIVES: This paper reports on physical activity of students in grades 3, 7,
      and 11 from two surveillance studies (from 2001 and 2005). METHODS: Randomly
      selected students (Study1 n=1730; Study2 n=2341) from randomly selected schools
      in Nova Scotia participated. Physical activity was measured for seven consecutive
      days using Actigraph accelerometers. Descriptive statistics were calculated for
      moderate, hard, and very hard intensity, and total minutes of physical activity.
      Between study, grade, and sex differences were determined using univariate
      Analyses of Variance. RESULTS: Students in Study2 were significantly less active
      (mean [SD]=531.0 [392.3] min/week) than Study1 (662.2 [495.1] min/week). Girls
      were significantly less active (525.4 [419.1] min/week) than boys (657.1 [460.3]
      min/week). Students in grade 11 were significantly less active (225.2 [171.1]
      min/week) than students in grade 7 (457.5 [227.2] min/week) who were
      significantly less active than students in grade 3 (1038.4 [387.6] min/week). A
      significant study-grade interaction indicated that compared to students in grades
      7 and 11, the level of physical activity in students in grade 3 was considerably
      lower in Study2 compared to Study1. CONCLUSIONS: Given the lower level of
      physical activity found in Study2, efforts at informing public policy and
      strategies that promote physical activity in children and youth should be made.

PMID- 19747939
TI  - Differences in transcriptomic profile and IgA repertoire between jejunal and
      ileal Peyer's patches.
AB  - In many species such as sheep and pig, there are two types of Peyer's patches
      (PP): several discrete patches in the jejunum and a long and continuous patch in
      the ileum. Most of the immunoglobulin A in the gut is generated by B-cells in the
      PP germinal centers. Moreover, swine like ovine ileal PP might be important for
      antigen independent B-cell repertoire diversification. We examined, by
      quantitative real-time PCR, the expression of 36 transcripts of antimicrobial
      peptides, chemokines, interleukines, Toll-like receptors and transcription
      factors from both PP and we highlighted the differences by a principal component
      analysis. Ileal PP was characterized by a higher mRNA expression of CCL28, IL5,
      IL10, TLR2 and TLR4 while jejunal PP showed higher mRNA expression of
      antimicrobial peptides, CCL25, FOXP3, IL4, T-Bet, TSLP and SOCS2. Then, we
      analyzed some VDJ rearrangements to assess immunoglobulin repertoire diversity in
      jejunal and ileal PP from weaned piglets. The IgA and IgM repertoires were more
      diverse in ileal than in jejunal piglet PP. All these results could be related to
      the rarefaction of interfollicular T-cell zone and the presence in ileal versus
      jejunal lumen of a more diversified microflora. These findings shed a light on
      the functional differences between both PP.

PMID- 19747940
TI  - Identification and characterization of the first reptilian CD9, and its
      expression analysis in response to bacterial infection.
AB  - In this study, a CD9 homologue in a reptile, Chinese soft-shelled turtle, has
      been cloned and identified for the first time. The full-length cDNA of turtle CD9
      was 1146bp and contained a 672bp open reading frame (ORF) coding for a protein of
      224 amino acids. Four transmembrane domains (TMs) divided the turtle CD9 into
      several parts: short N-, C-termini, an intracellular loop and two (small and
      large) extracellular loops (SEL and LEL). A CCG motif, a potential N-linked
      glycosylation site and 10 cysteine residues were well conserved. The deduced
      amino acid sequence analysis showed that the turtle CD9 shared 82% identity to
      duck CD9. Most of the differences were found in the LEL. Phylogenetic analysis
      showed that the turtle CD9 sequence clustered together with bird CD9 sequence. RT
      PCR analysis showed that turtle CD9 was ubiquitously expressed in liver, spleen,
      kidney, heart, blood and intestine tissues of un-infected turtles. Real-time PCR
      analysis further indicated that after Aeromonas hydrophila infection, the turtle
      CD9 mRNA was up-regulated in various tissues at 8h, and significantly up
      regulated during 8h to 7d. These results indicated that turtle CD9 may be
      involved in anti-bacterial immune response.

PMID- 19747941
TI  - Systematic telephone triage of possible 'swine' influenza leads to potentially
      serious misdiagnosis of infectious diseases.

PMID- 19747942
TI  - Insight into zinc signaling from dietary zinc deficiency.
AB  - Zinc is necessary for not only brain development but also brain function. Zinc
      homeostasis in the brain is tightly regulated by the brain barrier system and is
      not easily disrupted by dietary zinc deficiency. However, histochemically
      reactive zinc as revealed by Timm's staining is susceptible to zinc deficiency,
      suggesting that the pool of Zn(2+) can be reduced by zinc deficiency. The
      hippocampus is also susceptible to zinc deficiency in the brain. On the other
      hand, zinc deficiency causes abnormal glucocorticoid secretion from the adrenal
      cortex, which is observed prior to the decrease in extracellular zinc
      concentration in the hippocampus. The hippocampus is enriched with glucocorticoid
      receptors and hippocampal functions are changed by abnormal glucocorticoid
      secretion. Zinc deficiency elicits neuropsychological symptoms and affects
      cognitive performance. It may also aggravate glutamate excitotoxicity in
      neurological diseases. Abnormal glucocorticoid secretion is associated with these
      symptoms in zinc deficiency. Furthermore, the decrease in Zn(2+) pool may
      cooperate with glucocorticoid action in zinc deficiency. Judging from
      susceptibility of Zn(2+) pool in the brain to zinc deficiency, it is possible
      that the decrease in Zn(2+) pool in the peripheral tissues triggers abnormal
      glucocorticoid secretion. To understand the importance of zinc as a signaling
      factor, this paper analyzes the relationship among the changes in hippocampal
      functions, abnormal behavior and pathophysiological changes in zinc deficiency,
      based on the data from experimental animals.

PMID- 19747943
TI  - Relationship between grasping force and features of single-channel intramuscular
      EMG signals.
AB  - The surface electromyographic (sEMG) signal can be used for force prediction and
      control in prosthetic devices. Because of technological advances on implantable
      sensors, the use of intramuscular EMG (iEMG) is becoming a potential alternative
      to sEMG for the control of multiple degrees-of-freedom (DOF). An invasive system
      is not affected by crosstalk, typical of sEMG, and provides more stable and
      independent control sites. However, intramuscular recordings provide more local
      information because of their high selectivity, and may thus be less
      representative of the global muscle activity with respect to sEMG. This study
      investigates the capacity of selective single-channel iEMG recordings to
      represent the grasping force with respect to the use of sEMG with the aim of
      assessing if iEMG can be an effective method for proportional myoelectric
      control. sEMG and iEMG were recorded concurrently from 10 subjects who exerted
      six grasping force profiles from 0 to 25/50N. The linear correlation coefficient
      between features extracted from iEMG and force was approximately 0.9 and was not
      significantly different from the degree of correlation between sEMG and force.
      This result indicates that a selective iEMG recording is representative of the
      applied grasping force and can be used for proportional control.

PMID- 19747944
TI  - Approximate average head models for EEG source imaging.
AB  - We examine the performance of approximate models (AM) of the head in solving the
      EEG inverse problem. The AM are needed when the individual's MRI is not
      available. We simulate the electric potential distribution generated by cortical
      sources for a large sample of 305 subjects, and solve the inverse problem with
      AM. Statistical comparisons are carried out with the distribution of the
      localization errors. We propose several new AM. These are the average of many
      individual realistic MRI-based models, such as surface-based models or lead
      fields. We demonstrate that the lead fields of the AM should be calculated
      considering source moments not constrained to be normal to the cortex. We also
      show that the imperfect anatomical correspondence between all cortices is the
      most important cause of localization errors. Our average models perform better
      than a random individual model or the usual average model in the MNI space. We
      also show that a classification based on race and gender or head size before
      averaging does not significantly improve the results. Our average models are
      slightly better than an existing AM with shape guided by measured individual
      electrode positions, and have the advantage of not requiring such measurements.
      Among the studied models, the Average Lead Field seems the most convenient tool
      in large and systematical clinical and research studies demanding EEG source
      localization, when MRI are unavailable. This AM does not need a strict alignment
      between head models, and can therefore be easily achieved for any type of head
      modeling approach.

PMID- 19747945
TI  - The hypnospectrogram: an EEG power spectrum based means to concurrently overview
      the macroscopic and microscopic architecture of human sleep.
AB  - This study introduces a complementary tool for the description and evaluation of
      human sleep. The nocturnal sleep electroencephalographic (EEG) time-frequency
      analysis (TFA) plot (hypnospectrogram for short) is hereby proposed as a means to
      visualize both the macroscopic and the microscopic architecture of human sleep.
      It provides the ability to concurrently visually inspect the coarse sleep
      architecture, that is, the time-course of non-rapid eye movement (NREM) and REM
      stages, along with finer sleep elements such as slow and fast spindles, NREM
      delta distribution, REM alpha and beta, microarousals (MAs), and NREM cyclic
      alternating patterns (CAPs). Furthermore, the hypnospectrogram has the potential
      to provide visual quality of sleep (QoS) evaluation, as well as reveal the
      dominant rhythms and their transitions for every cerebral locus - as represented
      at the electrode space - during the night.

PMID- 19747946
TI  - A novel method for reliable nuclear antibody detection in tissue with high levels
      of pathology-induced autofluorescence.
AB  - Immunofluorescence is the basis for many techniques used to quantify phenomena in
      neuroscience research, in both normal and pathological tissue. Autofluorescence
      (non-specific, broad spectrum background fluorescence) is an unfortunate
      consequence of damage to brain tissue. Damage-induced autofluorescence
      potentially confounds analyses of tissue labeled with fluorescent markers in many
      experiments. This is especially problematic in protocols that utilize co
      localization methods such as BrdU/NeuN in which autofluorescence might lead to
      overestimates of the number of double-labeled cells. Techniques to reduce
      autofluorescence are variable and relatively ineffective in damaged brain tissue.
      Here we show using confocal microscopy that damage-induced autofluorescence does
      not co-localize with the nuclear specific markers DAPI or Hoechst. Further co
      localization of nuclear markers such as Ki67 or BrdU/NeuN with DAPI or Hoechst
      should serve to help discriminate between intended and spurious fluorescent
      signal.

PMID- 19747947
TI  - Evaluation of metaquant microdialysis for measurement of absolute concentrations
      of amphetamine and dopamine in brain: a viable method for assessing
      pharmacokinetic profile of drugs in the brain.
AB  - Direct measurement of absolute brain concentration of amphetamine and dopamine
      were obtained using metaquant (MQ) microdialysis, which achieves near 100%
      recovery, in the caudate nucleus. Conventional microdialysis monoprobes were also
      implanted in the caudate nucleus in the contralateral side of the same animals to
      compare the brain concentrations obtained from these two probe types. In addition
      plasma concentrations of amphetamine were obtained simultaneously from the same
      animals. The distribution of amphetamine in the plasma and of amphetamine and
      dopamine in both probe types followed same profile at each time interval. The
      basal dialysate concentration of dopamine in the caudate nucleus measured by MQ,
      was 9.40+/-0.60 nM, while measured by conventional microdialysis it was 6.35+/
      0.36 nM. This study demonstrates that MQ microdialysis is an appropriate method
      for determination of true extracellular levels of drugs and neurotransmitters in
      the brain, under dynamic conditions. Since these measurements, together with
      measurements of plasma concentrations of the drug, can be made in a single
      animal, the method can be used to study pharmacokinetic-pharmacodyamics profile
      of psychoactive agents.

PMID- 19747948
TI  - A novel HCV NS3 protease mutation selected by combination treatment of the
      protease inhibitor boceprevir and NS5B polymerase inhibitors.
AB  - Boceprevir (SCH 503034) is an orally active novel inhibitor of the hepatitis C
      virus (HCV) NS3 protease currently in clinical development for the treatment of
      hepatitis C. In this in vitro study, we demonstrate that combination of
      boceprevir with a nucleoside analog or a non-nucleoside HCV NS5B polymerase
      inhibitor was superior to treatment by single agents in inhibiting viral RNA
      replication in replicon cells. In the presence of boceprevir (at 5xEC(90)), the
      addition of 2'-C-methyl-adenosine or an indole-N-acetamide targeting the
      polymerase finger-loop site (at 1xEC(90)) significantly reduced the emergence of
      resistant replicon colonies. A higher dose (5xEC(90)) of either of the polymerase
      inhibitors in combination with boceprevir suppressed replicon resistance further
      to below detectable levels. Sequencing analysis of replicon cells selected by the
      combination treatment revealed known resistance mutations to the two polymerase
      inhibitors but no previously reported resistance mutations to boceprevir.
      Interestingly, a novel mutation (M175L) in the protease domain was identified.
      The dually resistant replicon cells were monitored for over 30 passages and
      sensitivity to polymerase inhibitors was found to decrease over time in a manner
      that correlated with the increasing prevalence of specific resistance mutations.
      Importantly, these cells remained sensitive to interferon-alpha and different
      classes of polymerase inhibitors. These findings support the rationale for
      clinical evaluation of combination treatment of HCV protease and polymerase
      inhibitors.

PMID- 19747949
TI  - Comparative structural, kinetic and inhibitor studies of Trypanosoma brucei
      trypanothione reductase with T. cruzi.
AB  - As part of a drug discovery programme to discover new treatments for human
      African trypanosomiasis, recombinant trypanothione reductase from Trypanosoma
      brucei has been expressed, purified and characterized. The crystal structure was
      solved by molecular replacement to a resolution of 2.3A and found to be nearly
      identical to the T. cruzi enzyme (root mean square deviation 0.6A over 482 Calpha
      atoms). Kinetically, the K(m) for trypanothione disulphide for the T. brucei
      enzyme was 4.4-fold lower than for T. cruzi measured by either direct (NADPH
      oxidation) or DTNB-coupled assay. The K(m) for NADPH for the T. brucei enzyme was
      found to be 0.77microM using an NADPH-regenerating system coupled to reduction of
      DTNB. Both enzymes were assayed for inhibition at their respective S=K(m) values
      for trypanothione disulphide using a range of chemotypes, including CNS-active
      drugs such as clomipramine, trifluoperazine, thioridazine and citalopram. The
      relative IC(50) values for the two enzymes were found to vary by no more than 3
      fold. Thus trypanothione reductases from these species are highly similar in all
      aspects, indicating that they may be used interchangeably for structure-based
      inhibitor design and high-throughput screening.

PMID- 19747950
TI  - Histone deacetylase inhibitors repress macrophage migration inhibitory factor
      (MIF) expression by targeting MIF gene transcription through a local chromatin
      deacetylation.
AB  - The cytokine macrophage migration inhibitory factor plays a central role in
      inflammation, cell proliferation and tumorigenesis. Moreover, macrophage
      migration inhibitory factor levels correlate with tumor aggressiveness and
      metastatic potential. Histone deacetylase inhibitors are potent antitumor agents
      recently introduced in the clinic. Therefore, we hypothesized that macrophage
      migration inhibitory factor would represent a target of histone deacetylase
      inhibitors. Confirming our hypothesis, we report that histone deacetylase
      inhibitors of various chemical classes strongly inhibited macrophage migration
      inhibitory factor expression in a broad range of cell lines, in primary cells and
      in vivo. Nuclear run on, transient transfection with macrophage migration
      inhibitory factor promoter reporter constructs and transduction with macrophage
      migration inhibitory factor expressing adenovirus demonstrated that trichostatin
      A (a prototypical histone deacetylase inhibitor) inhibited endogenous, but not
      episomal, MIF gene transcription. Interestingly, trichostatin A induced a local
      and specific deacetylation of macrophage migration inhibitory factor promoter
      associated H3 and H4 histones which did not affect chromatin accessibility but
      was associated with an impaired recruitment of RNA polymerase II and Sp1 and CREB
      transcription factors required for basal MIF gene transcription. Altogether, this
      study describes a new molecular mechanism by which histone deacetylase inhibitors
      inhibit MIF gene expression, and suggests that macrophage migration inhibitory
      factor inhibition by histone deacetylase inhibitors may contribute to the
      antitumorigenic effects of histone deacetylase inhibitors.

PMID- 19747951
TI  - Regulation and function of the cytosolic viral RNA sensor RIG-I in pancreatic
      beta cells.
AB  - Enteroviral infections are associated with type I diabetes. The mechanisms by
      which viruses or viral products such as double-stranded RNA (dsRNA) affect
      pancreatic beta cell function and survival remain unclear. We have shown that
      extracellular dsRNA induces beta cell death via Toll-like receptor-3 (TLR3)
      signaling whereas cytosolic dsRNA triggers the production of type I interferons
      and apoptosis via a TLR3-independent process. We presently examined expression of
      the intracellular viral RNA sensors, the RNA helicases RIG-I and MDA5, and
      documented the functionality of RIG-I in pancreatic beta cells. FACS-purified rat
      beta cells and islet cells from wild-type or TLR3(-/-) mice were cultured with or
      without the RIG-I-specific ligand 5'-triphosphate single-stranded RNA (5'triP
      ssRNA), the synthetic dsRNA polyI:C (PIC) or 5'OH-ssRNA (negative control); the
      RNA compounds were added in the medium or transfected in the cells using
      lipofectamine. RIG-I and MDA5 expression were determined by real-time RT-PCR. NF
      kappaB and IFN-beta promoter activation were studied in the presence or absence
      of a dominant-negative form of RIG-I (DN-RIG-I). Both extracellular (PICex) and
      intracellular (PICin) PIC increased expression of RIG-I and MDA5 in pancreatic
      beta cells. TLR3 deletion abolished PICex-induced up-regulation of the helicases
      in beta cells but not in dendritic cells. PICin-induced NF-kappaB and IFN-beta
      promoter activation were prevented by the DN-RIG-I. The RIG-I-specific ligand
      5'triP-ssRNA induced IFN-beta promoter activation and beta cell apoptosis. Our
      results suggest that the RIG-I pathway is present and active in beta cells and
      could contribute to the induction of insulitis by viral RNA intermediates.

PMID- 19747952
TI  - Inhibition of Legionella pneumophila PCR in respiratory samples: a quantitative
      approach.
AB  - Impurities in complex biological samples that persist through nucleic acid
      preparation can inhibit PCR or reduce the sensitivity and efficiency of PCR
      amplification and thus affect reliable results in PCR diagnostics. To obtain
      information on the incidence of inhibition events and on the magnitude of the
      loss of sensitivity, respectively, we devised a relative inhibition assay and
      examined 100 samples from patients with respiratory tract infections. As a
      reference, samples were spiked with Legionella (L.) pneumophila. Detection was by
      standard nucleic acid purification and subsequent real-time PCR. By comparing the
      crossing points of the fluorescent curves to those of an L. pneumophila standard
      dilution series, we were able to quantify the respective degrees of inhibition
      into several categories. We found complete inhibition in 2% of the samples. 12%
      were not reliably detected. 65% of the tested samples showed moderate to strong
      inhibition, but were still reliably detected, whereas in 21% of the samples no
      inhibition was observed. Except for a significantly higher inhibition in tracheal
      aspirates than in BAL samples, the degree of inhibition did not correlate with
      the physical properties of the respective sample. The relative inhibition assay
      established an unexpectedly broad distribution of the inhibition-degrees in
      inflammatory respiratory materials.

PMID- 19747953
TI  - Reading words and pseudowords in dyslexia: ERP and behavioural tests in English
      speaking adolescents.
AB  - The study reports neurophysiological and behavioural correlates of lexical
      decision processes in English speaking dyslexic and non-dyslexic readers. Nine
      dyslexic adolescents (ages 15.6-17.8) and 9 control (ages 15.4-19.3) adolescents
      were tested, and the event related potentials (ERPs) to words and pseudowords
      were recorded simultaneously with behavioural measures. As expected, both groups
      showed significantly lower accuracy and longer response times for the
      pseudowords. Furthermore, overall performance (in terms of lower accuracy and
      longer response times) was significantly worse for the dyslexic group. The ERP
      analysis indicated that the later positive peaks, P4 (around 400 ms from stimulus
      onset) and P5 (around 500 ms), were significantly delayed and attenuated for the
      dyslexic group. Analysis of the early ERP peaks recorded in the occipitotemporal
      region led to an interesting dissociation. The controls showed a left lateralised
      Condition effect, with the amplitude of P1 significantly smaller to words than
      pseudowords. By contrast, there was no such lexical effect for the dyslexic
      group, with equal P1 amplitudes for words and pseudowords, at the control level
      for pseudowords. The deviations in the early ERP components of dyslexics support
      the evidence of deficits in pre-lexical visual word form recognition within the
      first 110 ms of activation together with altered hemispheric asymmetry. In
      addition, the slowed and attenuated late ERP components and weaker behavioural
      performance of the dyslexic group highlight deficits in the later, cognitive,
      processing stages.

PMID- 19747954
TI  - The Bv8 gene from Bombina orientalis: molecular cloning, genomic organization and
      functional characterization of the promoter.
AB  - Bv8 is a secreted peptide from Bombina variegata skin glands with a molecular
      mass close to 8kDa that is conserved in fish, amphibians and mammals. Bv8 has
      diverse regulatory roles, including an involvement in hematopoiesis and
      immunomodulation. Here we report the genomic organization of the gene from
      Bombina orientalis coding for the Bv8 homolog (Bo8). It contains three exons
      separated by two large introns. Several putative transcription factor binding
      sites have been identified in the promoter sequence. Functional analysis of this
      region was performed using a yeast genetic system. The results indicate that the
      transcription factors AP-1, NF-kappaB and NFAT are involved in the regulation of
      the expression of Bo8. Hence, amphibians are a useful model for the study of
      transcriptional regulation of all Bv8 homologs.

PMID- 19747955
TI  - Islet neogenesis-associated protein-related pentadecapeptide enhances the
      differentiation of islet-like clusters from human pancreatic duct cells.
AB  - The differentiation of pancreatic ductal epithelial cells into beta-cells has
      been considered as an alternative method for increasing the number of islets for
      transplantation. Critical factors have been introduced into the in vitro
      differentiation protocol for pancreatic duct cells in order to enhance the
      production of beta-cells. Islet neogenesis-associated protein (INGAP) is an
      initiator of islet neogenesis and the peptide sequence 104-118 of INGAP has been
      shown to stimulate an increase in beta-cell mass in animals and also found in
      human pathological states involving islet neogenesis. To establish a novel method
      for the differentiation of beta-cells from human pancreatic duct cells with INGAP
      related pentadecapeptide (INGAP-PP), the pancreatic duct cells were isolated,
      purified and expanded in vitro and differentiated using a four-step protocol that
      included nicotinamide, exendin-4, transforming growth factor beta(1) and INGAP
      PP/Scrambled peptide (Scrambled-P). The production of islet-like clusters (ILCs)
      in the INGAP-PP group was significantly higher than that in the Scrambled-P
      control group after differentiation from an equal number of duct cells. The duct
      cells showed positive staining and expression for cytokeratin 19, pancreatic
      duodenal homeobox-1, nestin, and were negative for insulin and glucagon, as
      detected by both immunofluorescence and RT-PCR. Following differentiation the
      cells became insulin and glucagon positive. In addition, the ILCs from the INGAP
      PP group secreted higher levels of insulin and C-peptide than the Scrambled-P
      group under a high glucose challenge. We conclude that INGAP peptide enhances the
      in vitro differentiation of pancreatic duct cells into islet-like clusters.

PMID- 19747956
TI  - Ghrelin inhibits post-infarct myocardial remodeling and improves cardiac function
      through anti-inflammation effect.
AB  - Ghrelin is a novel growth hormone-releasing peptide, which has been shown to
      exert beneficial cardiac effects on chronic heart failure (CHF) recently. In this
      study, we attempted to investigate the mechanisms for the effect of ghrelin on
      ventricular remodeling following acute myocardial infarction (MI). Ligation of a
      coronary artery was used to create an MI in rats. One week after MI, ghrelin (100
      microg/kg) or saline was injected subcutaneously twice a day for 4 weeks. When
      compared to sham groups, ghrelin administration significantly decreased left
      ventricular (LV) remodeling in post-MI rats, as indicated by increased LV maximum
      rate of pressure, LV fractional shortening and scar thickness; and decreased LV
      end-diastolic pressure, LV end-systolic diameter, LV end-diastolic diameter and
      cardiocytocytes apoptosis. Moreover, ghrelin inhibited the inflammatory response,
      as shown by decreased mRNA and protein levels of interleukin (IL)-1beta and tumor
      necrosis factor-alpha (TNF-alpha). Subsequently, the expression of matrix
      metalloproteinase (MMP)-2 and MMP-9 were also inhibited by ghrelin injection.
      Ghrelin alleviates LV dysfunction and ventricular remodeling in post-MI rats.
      This suggests that the beneficial effects of ghrelin on CHF may result from an
      inhibition of the inflammatory response.

PMID- 19747957
TI  - Sensory and sympathetic nervous system control of white adipose tissue lipolysis.
AB  - Circulating factors are typically invoked to explain bidirectional communication
      between the CNS and white adipose tissue (WAT). Thus, initiation of lipolysis has
      been relegated primarily to adrenal medullary secreted catecholamines and the
      inhibition of lipolysis primarily to pancreatic insulin, whereas signals of body
      fat levels to the brain have been ascribed to adipokines such as leptin. By
      contrast, evidence is given for bidirectional communication between brain and WAT
      occurring via the sympathetic nervous system (SNS) and sensory innervation of
      this tissue. Using retrograde transneuronal viral tract tracers, the SNS outflow
      from brain to WAT has been defined. Functionally, sympathetic denervation of WAT
      blocks lipolysis to a variety of lipolytic stimuli. Using anterograde
      transneuronal viral tract tracers, the sensory input from WAT to brain has been
      defined. Functionally, these WAT sensory nerves respond electrophysiologically to
      increases in WAT SNS drive suggesting a possible neural negative feedback loop to
      regulate lipolysis.

PMID- 19747960
TI  - Upregulation of mitochondrial function and antioxidant defense in the
      differentiation of stem cells.
AB  - Stem cell research has received increasing attention due to their invaluable
      potentials in the clinical applications to cure degenerative diseases, genetic
      disorders and even cancers. A great number of studies have been conducted with an
      aim to elucidate the molecular mechanisms involved in the regulation of self
      renewal of stem cells and the mysterious circuits guiding them to differentiate
      into all kinds of progenies that can replenish the cell pools. However, little
      effort has been made in studying the metabolic aspects of stem cells.
      Mitochondria play essential roles in mammalian cells in the generation of ATP,
      Ca(2+) homeostasis, compartmentalization of biosynthetic pathways and execution
      of apoptosis. Considering the metabolic roles of mitochondria, they must be also
      critical in stem cells. This review is primarily focused on the biogenesis and
      bioenergetic function of mitochondria in the differentiation process and
      metabolic features of stem cells. In addition, the involvement of reactive oxygen
      species and hypoxic signals in the regulation of stem cell pluripotency and
      differentiation is also discussed.

PMID- 19747959
TI  - Progesterone regulation of primordial follicle assembly in bovine fetal ovaries.
AB  - Fertility in mammals is dependant on females having an adequate primordial
      follicle pool to supply oocytes for fertilization. The formation of primordial
      follicles is called ovarian follicular assembly. In rats and mice progesterone
      and estradiol have been shown to inhibit follicle assembly with assembly
      occurring after birth when the pups are removed from the high-steroid maternal
      environment. In contrast, primordial follicle assembly in other species, such as
      cattle and humans, occurs during fetal development before birth. The objective of
      the current study is to determine if progesterone levels regulate primordial
      follicle assembly in fetal bovine ovaries. Ovaries and blood were collected from
      bovine fetuses. Interestingly, ovarian progesterone and estradiol concentrations
      were found to decrease with increasing fetal age and correlated to increased
      primordial follicle assembly. Microarray analysis of fetal ovary RNA suggests
      that progesterone membrane receptor and estrogen nuclear receptor are expressed.
      Treatment of fetal bovine ovary cultures with a higher progesterone concentration
      significantly decreased primordial follicle assembly. Observations indicate that
      progesterone affects ovarian primordial follicle assembly in cattle, as it does
      in rats and mice.

PMID- 19747961
TI  - The forkhead factor FOXL2: a novel tumor suppressor?
AB  - FOXL2 is a gene encoding a forkhead transcription factor, whose germline
      mutations are responsible for the blepharophimosis ptosis epicanthus inversus
      syndrome. We have previously shown that expression levels of FOXL2 in a series of
      juvenile ovarian granulosa cell tumors (OGCTs) were markedly reduced. More
      recently, a whole-transcriptome 'next-generation' sequencing study has identified
      the somatic mutation p.Cys134Trp as recurring in adult OGCTs. This mutation may
      thus provide the tumor with either a striking proliferative potential or
      increased survival abilities. These studies of FOXL2 in OGCTs suggest that it may
      act as a tumor suppressor gene. This is in line with the fact that other forkhead
      transcription factors have already been involved in the etiology of cancer.
      Indeed, an in-depth review of existing data on FOXL2 reveals that its target
      genes and molecular partners can often be linked to cancer progression.

PMID- 19747958
TI  - Hormones in synergy: regulation of the pituitary gonadotropin genes.
AB  - The precise interplay of hormonal influences that governs gonadotropin hormone
      production by the pituitary includes endocrine, paracrine and autocrine actions
      of hypothalamic gonadotropin-releasing hormone (GnRH), activin and steroids.
      However, most studies of hormonal regulation of luteinizing hormone (LH) and
      follicle-stimulating hormone (FSH) in the pituitary gonadotrope have been limited
      to analyses of the isolated actions of individual hormones. LHbeta and FSHbeta
      subunits have distinct patterns of expression during the menstrual/estrous cycle
      as a result of the integration of activin, GnRH, and steroid hormone action. In
      this review, we focus on studies that delineate the interplay among these
      hormones in the regulation of LHbeta and FSHbeta gene expression in gonadotrope
      cells and discuss how signaling cross-talk contributes to differential
      expression. We also discuss how recent technological advances will help identify
      additional factors involved in the differential hormonal regulation of LH and
      FSH.

PMID- 19747962
TI  - MicroRNAs: Oncogenes, tumor suppressors or master regulators of cancer
      heterogeneity?
AB  - The realization that microRNAs are intimately linked to cancer pathogenesis has
      spawned an explosion of research activity in recent years. Their presence is not
      merely predictive of tumor origin and behavior, they are causally linked to the
      emergence and development of cancer by acting as oncogenes or tumor suppressors.
      The understanding of the functional consequences of altered microRNA expression
      in cancer is progressing rapidly, even though the prediction of microRNA targets
      is still a hit and miss process. MicroRNAs may not act primarily by strongly
      reducing the expression of a few prominent cancer-regulatory genes, but by
      influencing the properties of the network of which these regulators are a central
      part. By coordinately regulating many genes, microRNAs are exquisitely suited to
      act as stabilizers of networks and to prevent extreme variations in phenotype due
      to intrinsic and extrinsic disturbances. Many advanced tumors show defects in
      microRNA expression and processing, which could increase phenotypic variability
      within tumors. This allows small subsets of cells with altered characteristics to
      emerge, which can have grave consequences as typically a small fraction of tumor
      cells is responsible for metastasis and treatment resistance, and ultimately
      treatment failure. Investigating microRNAs from the perspective of master
      regulators of network stability in cancer calls for new experimental approaches
      and may help to understand causes of cancer heterogeneity and disease
      progression.

PMID- 19747963
TI  - Independent and parallel lateral transfer of DNA transposons in tetrapod genomes.
AB  - In animals, the mode of transmission of transposable elements is generally
      vertical. However, recent studies have suggested that lateral transfer has
      occurred repeatedly in several distantly related tetrapod lineages, including
      mammals. Using transposons extracted from the genome of the lizard Anolis
      carolinensis as probes, we identified four novel families of hAT transposons that
      share extremely high similarity with elements in other genomes including several
      mammalian lineages (primates, chiropters, marsupials), one amphibian and one
      flatworm, the planarian Schmidtea mediterranea. The discontinuous phylogenetic
      distribution of these hAT families, coupled with very low synonymous divergence
      between species, strongly suggests that these elements were laterally transferred
      to these different species. This indicates that the horizontal transfer of DNA
      transposons in vertebrates might be more common than previously thought. Yet, it
      appears that the transfer of DNA transposons did not occur randomly as the same
      genomes have been invaded independently by different, unrelated transposon
      families whereas others seem to be immune to lateral transfer. This suggests that
      some organisms might be intrinsically more vulnerable to DNA transposon lateral
      transfer, possibly because of a weakened defense against transposons or because
      they have developed mechanisms to tolerate their impact.

PMID- 19747964
TI  - Dosage form design and in vitro/in vivo evaluation of cevimeline extended-release
      tablet formulations.
AB  - The objective of the present work is to develop an extended-release dosage form
      of cevimeline. Two types of extended-release tablets (simple matrix tablets and
      press-coated tablets) were prepared and their potential as extended-release
      dosage forms were assessed. Simple matrix tablets have a large amount of
      hydroxypropylcellulose as a rate-controlling polymer and the matrix is
      homogeneous throughout the tablet. The press-coated tablets consisted of a matrix
      core tablet, which was completely surrounded by an outer shell containing a large
      amount of hydroxypropylcellulose. The simple matrix tablets could not sustain the
      release of cevimeline effectively. In contrast, the press-coated tablets showed a
      slower dissolution rate compared with simple matrix tablets and the release curve
      was nearly linear. The dissolution of cevimeline from the press-coated tablets
      was not markedly affected by the pH of the dissolution medium or by a paddle
      rotating speed over the range of 50-200 rpm. Furthermore, cevimeline was
      constantly released from the press-coated tablets in the gastrointestinal tract
      and the steady-state plasma drug levels were maintained in beagle dogs. These
      results suggested that the designed PC tablets have a potential for extended
      release dosage forms.

PMID- 19747965
TI  - Hydrogels of N-isopropylacrylamide copolymers with controlled release of a model
      protein.
AB  - Temperature- and pH-sensitive hydrogels, based on N-isopropylacrylamide (NiPAAm)
      and itaconic acid (IA), were synthesized by free radical crosslinking
      copolymerization in the presence of lipase from Candida rugosa. The samples were
      characterized for their sensitivity to the changes of external conditions and the
      ability to control the release of a hydrophilic model protein, lipase. These
      hydrogels were highly responsive to temperature and pH, at constant ionic
      strength. Parameters, such as the crosslinking degree and non-ionic/ionic
      (NiPAAm/IA) ratio, were found to impact the hydrogel structure, mechanical
      properties, morphology and swelling kinetics at different pH and temperatures.
      The hydrogels demonstrated protein loading efficiency as high as 95 wt%. Release
      studies of a hydrophilic model protein at a physiological temperature of 37
      degrees C were performed at different pH values. High dependence of lipase
      release kinetics on hydrogel structure and the environmental pH was found,
      showing generally low release rates, lower in acidic media (pH 2.20) and higher
      at higher pHs (6.80). Lipase activity was retained even after treatment
      conditions that would provoke denaturation of the enzyme if it was not protected
      in the gel. The obtained hydrogels were found suitable for releasing therapeutic
      proteins in a controlled manner at specific sites in gastrointestinal tract.

PMID- 19747966
TI  - Development of a binary lipid nanoparticles formulation of itraconazole for
      parenteral administration and controlled release.
AB  - The principal aim of this study was to develop an intravenous formulation of
      itraconazole (ITZ) using lipid nanoparticles based on binary mixture of liquid
      and solid lipids. Lipid nanoparticles were developed to provide the controlled
      release of ITZ as well as to improve the solubility of ITZ. Lipid nanoparticles
      were prepared with tristearin as a solid lipid, triolein as a liquid lipid, and a
      surfactant mixture of eggPC, Tween 80 and DSPE-PEG(2000). ITZ was incorporated at
      the concentration of 20mg/g. Lipid nanoparticles were manufactured by high
      pressure homogenization method. The particle size and polydispersity index (PI)
      of lipid nanoparticles were below 280 nm and 0.2, respectively. Zeta potentials
      and incorporation efficiencies of lipid nanoparticles were around -30 mV and
      above 80%, respectively. Lipid nanoparticles containing 1% of liquid lipid showed
      the smallest particles size and the highest incorporation efficiency. Results
      from SEM, DSC and PXRD revealed that ITZ in lipid nanoparticles exists in an
      amorphous state. Release rates were increased as the amount of liquid lipid in
      lipid core increased, demonstrating that the release of ITZ from lipid
      nanoparticles could be controlled by modulation of the amount of liquid lipid in
      lipid core. Pharmacokinetic studies were performed after intravenous
      administration of lipid nanoparticles in rats at the dose of 5mg/kg. The plasma
      concentration of ITZ was prolonged after intravenous administration of lipid
      nanoparticles. It is concluded that binary lipid nanoparticles could control the
      release and pharmacokinetic parameters of ITZ.

PMID- 19747967
TI  - Prediction of drug particle size and content uniformity in low-dose solid dosage
      forms.
AB  - Drug particle size distribution has a profound impact to the content uniformity
      in low-dose solid drug products. We derived theoretically the skewness of potency
      distribution as a function of particle size distribution and target dose. It was
      demonstrated that both skewness and coefficient of variation diverge
      simultaneously with inverse square root of the target dose. This scaling relation
      was observed in recent experiment and was verified by Monte Carlo (MC)
      simulation, which was employed for the first time to solve for the full potency
      distribution from a random retrieving model. When tested against the criteria
      from USP 905 uniformity of dosage units, MC simulation showed a striking
      anisotropic distribution of the data. This suggests a full-scale consideration of
      the potency distribution is necessary for evaluating the impacts from particle
      size distribution and the dose, as compared against the normality assumption used
      before. A nomograph of the median particle size and the dose that meets a 99%
      pass rate was constructed for the specification of particle size or the lowest
      dose limit. Furthermore, we showed quantitatively the lowest dose limit can be
      drastically reduced if a cut-off size is imposed by removing oversized particles.

PMID- 19747968
TI  - Development of a positively charged prednicarbate nanoemulsion.
AB  - A physically and chemically stable positively charged prednicarbate nanoemulsion
      was developed as a carrier system for the treatment of atopic dermatitis.
      Phytosphingosine was used to obtain the positive charge and also because of its
      supportive properties for the restoration of damaged skin. As production method
      high pressure homogenization was employed. The optimal concentrations of
      phytosphingosine, the oil phase, and the emulsifiers were investigated. The
      production was optimized by investigating the influence of homogenization cycles,
      homogenization pressure, production temperature and type of homogenizer with
      respect to particle size, physical stability of the emulsions and chemical
      stability of prednicarbate. From the results the best formulation and the most
      appropriate production parameters were identified. In addition it could be shown
      that during high pressure homogenization the drug is relocated from the inner oil
      phase of the emulsion towards the stabilizer layer, which could be shown by an
      increase in chemical stability of prednicarbate. The efficiency of incorporation
      is influenced by the energy input during homogenization (e.g. number of
      homogenization cycles) but also by the production temperature. It was found that
      the nanoemulsions should be produced at elevated temperatures, with low
      homogenization pressures but higher numbers of homogenization cycles (e.g. 300
      bar and 10 cycles). The results prove that the efficiency of high pressure
      homogenization should not only be judged by investigating the particle size and
      the physical stability of the emulsions alone, but also by assessing the chemical
      stability of the incorporated drug.

PMID- 19747969
TI  - Comparison of anti-tumor efficacy of paclitaxel delivered in nano- and
      microparticles.
AB  - This research compares the anti-tumor efficacy of paclitaxel delivered
      intratumorally in PLGA nanoparticles, microparticles, or the commercial
      Paclitaxel Injection((R)). The hypothesis of the research is that larger PLGA
      microparticles adhere to mucus on the cell surface, release paclitaxel locally,
      and enhance cellular association of paclitaxel. PLGA-paclitaxel particles of mean
      diameters 315 nm, 1 microm, and 10 microm were prepared and their drug content,
      in vitro release, and cellular association of paclitaxel into 4T1 cells
      quantified. These particles were injected intratumorally into tumor xenografts,
      and the tumor volumes monitored over 13 days. Mean tumor volumes of the groups
      that received placebo and the 315 nm nanoparticles increased 2 and 1.5 times,
      respectively. Tumor growth was arrested in groups that received 1 microm and 10
      microm microparticles. Additional cell culture studies were performed to test the
      hypothesis. The size-dependent increase in cellular concentration of paclitaxel
      was independent of duration of incubation of PLGA particles with 4T1 cells, and
      was enhanced 1.5 times by coating the particles or 4T1 cells with mucin. These
      particles were not internalized by clathrin-mediated endocytosis or
      macropinocytosis. In conclusion, PLGA microparticles sustained drug release,
      increased cellular concentration, and enhanced anti-tumor efficacy of paclitaxel
      compared to nanoparticles and Paclitaxel Injection.

PMID- 19747970
TI  - Chemical enhancer solubility in human stratum corneum lipids and enhancer
      mechanism of action on stratum corneum lipid domain.
AB  - Previously, chemical enhancer-induced permeation enhancement on human stratum
      corneum (SC) lipoidal pathway at enhancer thermodynamic activities approaching
      unity in the absence of cosolvents (defined as Emax) was determined and
      hypothesized to be related to the enhancer solubilities in the SC lipid domain.
      The objectives of the present study were to (a) quantify enhancer uptake into SC
      lipid domain at saturation, (b) elucidate enhancer mechanism(s) of action, and
      (c) study the SC lipid phase behavior at Emax. It was concluded that direct
      quantification of enhancer uptake into SC lipid domain using intact SC was
      complicated. Therefore a liposomal model of extracted human SC lipids was used.
      In the liposome study, enhancer uptake into extracted human SC lipid liposomes
      (EHSCLL) was shown to correlate with Emax. Attenuated total reflectance Fourier
      transform infrared spectroscopy (ATR-FTIR) and differential scanning calorimetry
      (DSC) were used to evaluate lipid phase alterations in enhancer-treated intact
      SC. IR spectra demonstrated an increase in the lipid domain fluidity and DSC
      thermograms indicated a decrease in the phase transition temperature with
      increasing Emax. These results suggest that the enhancer mechanism of action is
      through enhancer intercalation into SC intercellular lipids and subsequent lipid
      lamellae fluidization related to enhancer lipid concentration.

PMID- 19747972
TI  - Mitochondria: joining forces to thwart cell death.
AB  - Mitochondria are highly dynamic organelles that undergo constant cycles of fusion
      and fission. An additional level of regulation of mitochondrial function, which
      is particularly important in neurons, is their active transport along
      microtubules. Recent evidence suggests that the mitochondrial fusion/fission
      machinery as well as the molecular motors responsible for their movement
      constitute powerful regulatory control points that directly impact metabolism and
      regulation of cell death. This is true for not only apoptosis, but also for
      excitotoxicity where calcium overload is a major component of the cell death
      process. In this review, we will describe the molecular mechanisms regulating
      fusion and fission and how this impinges on cell survival in the context of acute
      neuronal injury.

PMID- 19747971
TI  - Proteolysis in the SOS response and metal homeostasis in Escherichia coli.
AB  - Proteolysis is used by all forms of life for shaping the proteome in response to
      adverse environmental conditions in order to ensure optimal survival. Here we
      will address the role of proteolysis in helping cells respond to environmental
      stress, with a focus on the impact of proteolysis under DNA-damaging conditions
      and in maintenance of cellular homeostasis in response to metal exposure in
      bacteria.

PMID- 19747973
TI  - Mitochondrial trafficking and morphology in neuronal injury.
AB  - Alterations in mitochondrial function may have a central role in the pathogenesis
      of many neurodegenerative diseases. The study of mitochondrial dysfunction has
      typically focused on ATP generation, calcium homeostasis and the production of
      reactive oxygen species. However, there is a growing appreciation of the dynamic
      nature of mitochondria within cells. Mitochondria are highly motile organelles,
      and also constantly undergo fission and fusion. This raises the possibility that
      impairment of mitochondrial dynamics could contribute to the pathogenesis of
      neuronal injury. In this review we describe the mechanisms that govern
      mitochondrial movement, fission and fusion. The key proteins that are involved in
      mitochondrial fission and fusion have also been linked to some inherited
      neurological diseases, including autosomal dominant optic atrophy and Charcot
      Marie-Tooth disease 2A. We will discuss the evidence that altered movement,
      fission and fusion are associated with impaired neuronal viability. There is a
      growing collection of literature that links impaired mitochondrial dynamics to a
      number of disease models. Additionally, the concept that the failure to deliver a
      functional mitochondrion to the appropriate site within a neuron could contribute
      to neuronal dysfunction provides an attractive framework for understanding the
      mechanisms underlying neurologic disease. However, it remains difficult to
      clearly establish that altered mitochondrial dynamics clearly represent a cause
      of neuronal dysfunction.

PMID- 19747974
TI  - Halotolerant and halophilic fungi.
AB  - Extreme environments have for long been considered to be populated almost
      exclusively by prokaryotic organisms and therefore monopolized by
      bacteriologists. Solar salterns are natural hypersaline environments
      characterized by extreme concentrations of NaCl, often high concentrations of
      other ions, high uv irradiation and in some cases extremes in pH. In 2000 fungi
      were first reported to be active inhabitants of solar salterns. Since then many
      new species and species previously known only as food contaminants have been
      discovered in hypersaline environments around the globe. The eukaryotic
      microorganism most studied for its salt tolerance is Saccharomyces cerevisiae.
      However, S. cerevisiae is rather salt sensitive and not able to adapt to
      hypersaline conditions. In contrast, some species like Debaryomyces hansenii,
      Hortaea werneckii, and Wallemia ichthyophaga have been isolated globally from
      natural hypersaline environments. We believe that all three are more suitable
      model organisms to study halotolerance in eukaryotes than S. cerevisiae.
      Furthermore, they belong to different and distant taxonomic groups and have
      developed different strategies to cope with the same problems of ion toxicity and
      loss of water.

PMID- 19747975
TI  - Evolutionary relationships between aquatic anamorphs and teleomorphs: Tricladium
      and Varicosporium.
AB  - Tricladium, with 21 accepted species, is the largest genus of aquatic
      hyphomycetes. It encompasses species with dematiaceous as well as mucedinaceous
      colonies. Conidiogenesis is thalloblastic; conidiogenous cells proliferate
      percurrently or sympodially. Conidia have typically two alternate primary lateral
      branches. Fontanospora and Variocladium are segregates of Tricladium, differing
      by conidial branching. Varicosporium comprises nine species, one not well known.
      Conidiogenesis is blastic or thalloblastic, conidiogenous cells proliferate
      sympodially or are determinate; conidia regularly produce primary and secondary
      branches and often fragment into part conidia. Molecular analyses on the 28S rDNA
      of 86 isolates, including 16 species of Tricladium, five species of
      Varicosporium, two species of Fontanospora and one species of Variocladium, place
      these hyphomycetes within Helotiales. Tricladium is polyphyletic and placed in
      six clades; Varicosporium is polyphyletic and placed in three clades;
      Fontanospora is polyphyletic within a single clade. Variocladium is placed with
      poor support as a sister taxon to Varicosporium giganteum, Hymenoscyphus scutula
      and Torrendiella eucalypti.

PMID- 19747976
TI  - Combined immersion and oral vaccination of Vietnamese catfish (Pangasianodon
      hypophthalmus) confers protection against mortality caused by Edwardsiella
      ictaluri.
AB  - Edwardsiella ictaluri septicemia occurs worldwide and causes high mortality and
      considerable economic damage to the catfish industry especially in Vietnam and
      the USA. To control Edwardsiella septicemia farmers extensively use antibiotics
      and various vaccination methods. Vaccination with inactivated vaccines has come
      with variable efficacy. In this trial the results of an approach of controlling
      Edwardsiella septicemia of Tra catfish (Pangasianodon hypophthalmus) in Vietnam
      through vaccination via mucosal surfaces are presented. The results show that a
      combination of primary vaccination by immersion with inactivated E. ictaluri
      followed by an oral boost with a formulated antigen preparation induces a
      statistically significant level of protection against mortality caused by
      experimental infection 4 weeks post-boost. Fish immunized by immersion only show
      significantly lower level of protection but significantly higher than the
      controls. Repeated boosts result in improved duration of immunity with a relative
      percent survival (RPS) of 47% at 90% control mortality. The immunization
      procedure provides an alternative for disease control through vaccination.

PMID- 19747977
TI  - Molecular control of facial morphology.
AB  - We present a developmental perspective on the concept of phylotypic and
      phenotypic stages of craniofacial development. Within orders of avians and
      mammals, a phylotypic period exists when the morphology of the facial prominences
      is minimally divergent. We postulate that species-specific facial variations
      arise as a result of subtle shifts in the timing and the duration of molecular
      pathway activity (e.g., heterochrony), and present evidence demonstrating a
      critical role for Wnt and FGF signaling in this process. The same molecular
      pathways that shape the vertebrate face are also implicated in craniofacial
      deformities, indicating that comparisons between and among animal species may
      represent a novel method for the identification of human craniofacial disease
      genes.

PMID- 19747979
TI  - Chikungunya: a bending reality.
AB  - Chikungunya fever is an acute illness caused by the arbovirus Chikungunya virus.
      The virus is transmitted primarily in a sylvatic cycle involving the Aedes
      mosquitoes. Since 2005, a Chikungunya fever outbreak of unprecedented magnitude
      occurred on several Indian Ocean islands. Since then, the disease has spread to
      many parts of the world due to imported cases among travellers returning from
      epidemic areas. Chikungunya virus causes a wide spectrum of illness including
      fever, a characteristic rash, disabling joint symptoms which can sometimes become
      severe that lasts months. This review summarises on this history of Chikungunya
      fever, host specificity, the characteristics of Chikungunya virus, clinical
      features of disease and current control measures. It focuses on how the re
      emergence of an old changed the outlook of managing arboviral diseases in the
      present social and public health context.

PMID- 19747978
TI  - Cryptococcus neoformans cryoultramicrotomy and vesicle fractionation reveals an
      intimate association between membrane lipids and glucuronoxylomannan.
AB  - Cryptococcus neoformans is an encapsulated pathogenic fungus. The cryptococcal
      capsule is composed of polysaccharides and is necessary for virulence. It has
      been previously reported that glucuronoxylomannan (GXM), the major capsular
      component, is synthesized in cytoplasmic compartments and transported to the
      extracellular space in vesicles, but knowledge on the organelles involved in
      polysaccharide synthesis and traffic is extremely limited. In this paper we
      report the GXM distribution in C. neoformans cells sectioned by
      cryoultramicrotomy and visualized by transmission electron microscopy (TEM) and
      polysaccharide immunogold staining. Cryosections of fungal cells showed high
      preservation of intracellular organelles and cell wall structure. Incubation of
      cryosections with an antibody to GXM revealed that cytoplasmic structures
      associated to vesicular compartments and reticular membranes are in close
      proximity to the polysaccharide. GXM was generally found in association with the
      membrane of intracellular compartments and within different layers of the cell
      wall. Analysis of extracellular fractions from cryptococcal supernatants by
      transmission electron microscopy in combination with serologic, chromatographic
      and spectroscopic methods revealed fractions containing GXM and lipids. These
      results indicate an intimate association of GXM and lipids in both intracellular
      and extracellular spaces consistent with polysaccharide synthesis and transport
      in membrane-associated structures.

PMID- 19747980
TI  - The dynamic nature of Bruch's membrane.
AB  - Bruch's membrane (BM) is a unique pentalaminar structure, which is strategically
      located between the retinal pigment epithelium (RPE) and the fenestrated
      choroidal capillaries of the eye. BM is an elastin- and collagen-rich
      extracellular matrix that acts as a molecular sieve. BM partly regulates the
      reciprocal exchange of biomolecules, nutrients, oxygen, fluids and metabolic
      waste products between the retina and the general circulation. Accumulating
      evidence suggests that the molecular, structural and functional properties of BM
      are dependent on age, genetic constitution, environmental factors, retinal
      location and disease state. As a result, part of the properties of BM are unique
      to each human individual at a given age, and therefore uniquely affect the
      development of normal vision and ocular disease. The changes occurring in BM with
      age include increased calcification of elastic fibres, increased cross-linkage of
      collagen fibres and increased turnover of glycosaminoglycans. In addition,
      advanced glycation end products (AGEs) and fat accumulate in BM. These age
      related changes may not only influence the normal age-related health of
      photoreceptor cells, but also the onset and progression of diseases like
      retinitis pigmentosa (RP) and age-related macular degeneration (AMD).
      Undoubtedly, BM is the site of drusen development. Confluent drusen and
      uncontrolled activation of the complement cascade are most likely the first signs
      of AMD. Furthermore, the nature of adhesive interactions between the RPE and BM
      are instrumental in the development of retinal detachments and proliferative
      retinal disease. Finally, BM is passively or actively involved in a range of
      other retinal disorders such as Pseudoxanthoma elasticum (PXE), Sorsby's Fundus
      Dystrophy and Malattia Leventinese. Here, we review the dynamic nature of Bruch's
      membrane, from molecule to man, during development, aging and disease. We propose
      a simple and straightforward nomenclature for BM deposits. Finally, we attempt to
      correlate recently published mRNA expression profiles of the RPE and choroid with
      molecular, structural and functional properties of BM. Our review may shed light
      on the complex involvement of BM in retinal pathology, notably age-related
      macular degeneration.

PMID- 19747981
TI  - Biological and biochemical characterization of two new PLA2 isoforms Cdc-9 and
      Cdc-10 from Crotalus durissus cumanensis snake venom.
AB  - This work reports the purification, biological characterization and amino acid
      sequence of two new basic PLA(2) isoforms, Cdc-9 and Cdc-10, purified from the
      Crotalus durissus cumanensis venom by one step analytical chromatography reverse
      phase HPLC. The molecular masses of the PLA(2) were 14,175+/-2.7 Da for Cdc-9 and
      14,228+/-3.5 Da for Cdc-10 both deduced by primary structure and confirmed by
      MALDI-TOF. The isoforms presented an amino acid sequence of 122 amino acid
      residues, being Cdc-9: SLVQFNKMIK FETRKSGLPF YAAYGCYCGW GGQRPKDATD RCCFVHDCCY
      GKVAKCNTKW DIYSYSLKSG YITCGKGTWC KEQICECDRV AAECLRRSLS TYKNEYMFYP DSRCREPPEY TC
      with pI value of 8.25 and Cdc-10: SLLQFNKMIK FETRKSGVPF YAAYGCYCGW GGRRPKDPTD
      RCCFVHDCCY GKLTKCNTKW DIYSYSLKSG YITCGKGTWC KEQICECDRV AAECLRRSLN TYKNEYMFYP
      DSRCRGPPEY TC with a pI value of 8.46, showing highly conserved Ca(2+)-binding
      and catalytic sites. The PLA(2) activity decreased when the isoforms Cdc-9 and
      Cdc-10 were incubated with 4-bromophenacyl bromide (p-BPB), anhydrous acetic acid
      and p-nitrobenzene sulfonyl fluoride (NBSF) when compared with the activity of
      both native isoforms. In mice, the PLA(2) isoforms Cdc-9 and Cdc-10 induced
      myonecrosis and edema. Myotoxic and edema activities were reduced after treatment
      of the isoforms with p-BPB; acetylation of the lysine residues and the treatment
      of PLA(2) with NBSF have also induced edema reduction. However, p-BPB strongly
      diminishes the local and systemic myotoxic effects.

PMID- 19747982
TI  - Acute acalculous cholecystitis: a review.
AB  - Although recognized for more than 150 years, acute acalculous cholecystitis (AAC)
      remains an elusive diagnosis. This is likely because of the complex clinical
      setting in which this entity develops, the lack of large prospective controlled
      trials that evaluate various diagnostic modalities, and thus dependence on a
      small data base for clinical decision making. AAC most often occurs in critically
      ill patients, especially related to trauma, surgery, shock, burns, sepsis, total
      parenteral nutrition, and/or prolonged fasting. Clinically, AAC is difficult to
      diagnose because the findings of right upper-quadrant pain, fever, leukocytosis,
      and abnormal liver tests are not specific. AAC is associated with a high
      mortality, but early diagnosis and intervention can change this. Early diagnosis
      is the crux of debate surrounding AAC, and it usually rests with imaging
      modalities. There are no specific criteria to diagnose AAC. Therefore, this
      review discusses the imaging methods most likely to arrive at an early and
      accurate diagnosis despite the complexities of the radiologic modalities. A
      pragmatic approach is vital. A timely diagnosis will depend on a high index of
      suspicion in the appropriate patient, and the combined results of clinical
      findings (admittedly nonspecific), plus properly interpreted imaging. Sonogram
      (often sequential) and hepatic iminodiacetic acid scans are the most reliable
      modalities for diagnosis. It is generally agreed that cholecystectomy is the
      definitive therapy for AAC. However, at times a diagnostic/therapeutic drainage
      via interventional radiology/surgery may be necessary and life-saving, and may be
      the only treatment needed.

PMID- 19747983
TI  - Image of the month. Intramural dissection of the esophagus in a young man
      presenting with hematemesis.

PMID- 19747984
TI  - An urgent call to the magnetic resonance scanner: potential dangers of capsule
      endoscopy.

PMID- 19747985
TI  - Acute pancreatitis during pregnancy.
AB  - BACKGROUND & AIMS: Acute pancreatitis is rare during pregnancy; limited data are
      available about maternal and fetal outcomes. We investigated the effects of acute
      pancreatitis during pregnancy on fetal outcome. METHODS: This retrospective
      cohort study, performed at a single academic center, included consecutive
      pregnant women who presented with (n = 96) or developed acute pancreatitis in the
      hospital (n = 7) in 2000-2006 (mean age, 26 y). Patient histories and clinical
      data were collected from medical records. RESULTS: Of the 96 patients with
      spontaneous pancreatitis, 4 had complications: 1 patient in the first trimester
      had acute peripancreatic fluid collection, and 3 patients in the third trimester
      developed disseminated vascular coagulation (DIC). None of these patients
      achieved term pregnancy, and 1 of the patients with DIC died. Endoscopic
      retrograde cholangiopancreatography (ERCP) was performed in 23 patients with
      acute pancreatitis; post-ERCP pancreatitis was diagnosed in 4 patients (a total
      of 11 patients developed ERCP-associated pancreatitis). Term pregnancy was
      achieved in 73 patients (80.2%). Patients who developed pancreatitis in the first
      trimester had the lowest percentage of term pregnancy (60%) and highest risks of
      fetal loss (20%) and preterm delivery (16%). Of the patients with pancreatitis in
      the second and third trimesters, only one had fetal loss. Fetal malformations
      were not observed. CONCLUSIONS: The majority of pregnant patients with acute
      pancreatitis did not have complications; most adverse fetal outcomes (fetal loss
      and preterm delivery) occurred during the first trimester. Acute pancreatitis,
      complicated by DIC, occurred most frequently in the third trimester and was
      associated with poor fetal and maternal outcomes.

PMID- 19747986
TI  - Induction pegylated interferon alfa-2b in combination with ribavirin in patients
      with genotypes 1 and 4 chronic hepatitis C: a prospective, randomized,
      multicenter, open-label study.
AB  - BACKGROUND & AIMS: Standard of care (SOC) treatment for chronic hepatitis C (CHC)
      involves weekly pegylated (PEG) interferon plus weight-based ribavirin with
      resultant sustained virologic response (SVR) rates at or near 50% for genotypes 1
      and 4 virus. Induction therapy with higher doses of PEG interferon may improve
      first-phase viral kinetics and thus improve the overall SVR in genotypes 1 and 4
      patients. METHODS: This multicenter, randomized, open-label trial enrolled
      treatment-naive genotypes 1- and 4-infected CHC patients to either initial
      induction therapy versus SOC. The induction group received PEG interferon alfa-2b
      3.0 mcg/kg/wk for 12 weeks followed by PEG interferon alfa-2b 1.5 mcg/kg/wk for
      36 weeks and 13 +/- 2 mg/kg ribavirin daily for 48 weeks. SOC patients received
      PEG interferon alfa-2b 1.5 mcg/kg weekly for 48 weeks and 13 +/- 2 mg/kg
      ribavirin daily for 48 weeks. The primary end point was SVR. RESULTS: There were
      610 patients enrolled throughout the United States. Complete early virologic
      response was 62.6% versus 57.7% in induction versus SOC (NS). Overall SVR was 32%
      in induction versus 29% in SOC group (NS). Dose reduction of either PEG
      interferon (24.1% vs 23.8%) or ribavirin (26.8% vs 25.1%) was similar between the
      2 groups. There was a trend toward a significant difference when comparing the
      SVR in induction therapy in patients weighing more than 85 kg versus those
      receiving SOC (38% vs 28%; P = .08). CONCLUSIONS: Induction therapy does not
      enhance complete early virologic response or SVR rates in a predominantly
      genotype 1 CHC population compared with SOC therapy.

PMID- 19747987
TI  - Removal of bile duct foreign body by using spyglass and spybite.

PMID- 19747988
TI  - Lack of association between hepatitis C infection and chronic kidney disease.
AB  - BACKGROUND & AIMS: Chronic kidney disease (CKD) can have a negative impact on the
      natural history of hepatitis C virus infection (HCV) infection; patients with HCV
      and CKD often have adverse outcomes. We evaluated a large and geographically
      diverse group of patients to determine whether HCV status has an independent
      effect on the risk of developing CKD. METHODS: We conducted a cohort study of
      167,569 patients included in a national health care claims database from January
      1, 2003-December 31, 2006, with a mean follow-up of 25.3 months. We used
      multivariable logistic regression analyses to measure the independent effect of
      HCV status on the baseline prevalence of and progression to CKD (estimated
      glomerular filtration rate, <60 mL/min/1.73 m(2)). RESULTS: The baseline
      prevalence of CKD was similar in patients with versus those without HCV (5.3% vs
      5.1%, P = .3). Similarly, among patients with preserved renal function at
      baseline (n = 82,629), there was no difference in the overall progression to CKD
      in patients with versus those without HCV (3.8% vs 3.5%, P = .1). HCV status was
      not associated with progression to CKD, even after adjusting for patient
      demographics, comorbidities, and use of relevant medications (odds ratio, 0.92;
      95% confidence interval, 0.79-1.08). CONCLUSIONS: We found no association between
      HCV and risk of development of CKD. These data are relevant in counseling HCV
      patients regarding the impact of HCV on renal function.

PMID- 19747989
TI  - Alterations in serum levels of inflammatory cytokines (TNF, IL-1alpha, IL-1beta
      and IL-1Ra) 20 years after sulfur mustard exposure: Sardasht-Iran cohort study.
AB  - Mustard gas, even in low doses, has the ability to inflict damage in multiple
      organs especially the skin, eyes, as well as the respiratory tract. This damage
      may cause many complications which persist during the lifespan of exposed
      subjects. Pro-inflammatory cytokines including TNF, IL-1alpha, IL-1beta and IL
      1Ra cause systemic inflammatory reactions and numerous changes including altered
      cell signaling and migration, changes in cytokine production and fever. The aim
      of this study was to determine the serum levels of these cytokines in subjects
      who were exposed to mustard gas 20 years ago in comparison with an unexposed
      control group. In this historical cohort study 368 sulfur mustard (SM) exposed
      participants from Sardasht and 126 age-matched unexposed volunteers from Rabat (a
      nearby town) as controls were chosen by a random systematic sampling. The serum
      concentrations of IL-1alpha, IL-1beta, IL-1Ra and TNF were measured by a sandwich
      ELISA technique. Median of the serum levels of cytokines TNF, IL-1alpha, IL-1beta
      and IL-1Ra in the control group was 23.79, 1.89, 1.91 and 32.9 pg/ml
      respectively, while in the SM-exposed participants these values were 11.11, 0.81,
      1.73 and 26.7 pg/ml respectively. The serum pro-inflammatory cytokine levels were
      significantly lower in the exposed group than in controls (p<0.01). There was
      also significant positive correlation between concentration of all of mentioned
      cytokines, the strongest being between IL-1beta and TNF (r=0.809 in the control
      group). The observed down-regulation of pro-inflammatory cytokines should be
      considered in interpretation of diagnosis and therapeutic measures taken to
      improve clinical complications.

PMID- 19747990
TI  - The gamma class of carbonic anhydrases.
AB  - Homologs of the gamma class of carbonic anhydrases, one of five independently
      evolved classes, are found in the genomic sequences of diverse species from all
      three domains of life. The archetype (Cam) from the Archaea domain is a
      homotrimer of which the crystal structure reveals monomers with a distinctive
      left-handed parallel beta-helix fold. Histidines from adjacent monomers ligate
      the three active site metals surrounded by residues in a hydrogen bond network
      essential for activity. Cam is most active with iron, the physiologically
      relevant metal. Although the active site residues bear little resemblance to the
      other classes, kinetic analyses indicate a two-step mechanism analogous to all
      carbonic anhydrases investigated. Phylogenetic analyses of Cam homologs derived
      from the databases show that Cam is representative of a minor subclass with the
      great majority belonging to a subclass (CamH) with significant differences in
      active site residues and apparent mechanism from Cam. A physiological function
      for any of the Cam and CamH homologs is unknown, although roles in transport of
      carbon dioxide and bicarbonate across membranes has been proposed.

PMID- 19747991
TI  - Decreased in the number and function of circulation endothelial progenitor cells
      in patients with avascular necrosis of the femoral head.
AB  - INTRODUCTION: Once non-traumatic avascular necrosis of the femoral head (ANFH)
      happened, vascular impairment and feeble collateral circulation are followed by
      poor outcomes. Circulating endothelial progenitor cells (EPCs) may substantially
      contribute to vascular homeostasis such as vascular repair and new blood vessel
      growth. We investigated whether abnormalities in EPCs levels and functions are
      present in ANFH patients. METHODS: 54 ANFH patients were enrolled, including
      steroid-induced (n=21), alcohol-induced (n=15) and idiopathic ANFH (n=18), and 30
      healthy subjects as control (HC). The numbers of circulation EPCs were determined
      by fluorescence-activated cell-sorting (FACS) analysis. EPCs cultured from
      peripheral blood mononuclear cells on fibronectin to induce the expression of
      receptors for acetylated low-density lipoprotein and ulex-lectin. EPCs colony
      forming units (CFUs) were observed from 54 patients and 30 healthy controls.
      Migratory capacity to chemo-attractants (vascular endothelial growth factor)
      cellular senescence levels and in vitro angiogenesis ability were assessed in age
      matched subjects (n=10 per groups). RESULTS: Mean numbers of circulating EPC were
      1460+/-265 cells/ml in HC, 545+/-177 in ANFH, (P<0.001). Mean numbers of CFUs
      were 26.2+/-6.2 in HC, 19.6+/-7.7 in ANFH,(P<0.001). Although there were not
      significant differences in circulating EPC and CFUs among the steroid-induced,
      alcohol-induced or idiopathic three groups, all these risk factors contributed to
      the decreased circulating EPCs numbers and CFUs. In addition, EPCs from ANFH
      patients showed reduced migratory capacity and increased cellular senescence
      compared with EPCs from normal subjects, furthermore the ability of angiogenesis
      in vitro was also impaired. CONCLUSION: Circulating endothelial progenitor cells
      (EPCs) numbers and functions are reduced in ANFH patients, suggesting that risk
      factors of ANFH may alter EPCs biology in angiogenesis and vascular repair.

PMID- 19747992
TI  - A multicentre, retrospective case-control study assessing the role of trabecular
      bone score (TBS) in menopausal Caucasian women with low areal bone mineral
      density (BMDa): Analysing the odds of vertebral fracture.
AB  - INTRODUCTION: The trabecular bone score (TBS) is a new parameter that is
      determined from grey level analysis of DXA images. It relies on the mean
      thickness and volume fraction of trabecular bone microarchitecture. This was a
      preliminary case-control study to evaluate the potential diagnostic value of TBS,
      both alone and combined with bone mineral density (BMDa), in the assessment of
      vertebral fracture. METHODS: Out of a subject pool of 441 Caucasian,
      postmenopausal women between the ages of 50 and 80 years, we identified 42 women
      with osteoporosis-related vertebral fractures, and compared them with 126 age
      matched women without any fractures (1 case: 3 controls). Primary outcomes were
      BMDa and TBS. Inter-group comparisons were undertaken using Student's t-tests and
      Wilcoxon signed ranks tests for parametric and non-parametric data, respectively.
      Odds ratios for vertebral fracture were calculated for each incremental one
      standard deviation decrease in BMDa and TBS, and areas under the receiver
      operating curve (AUC) calculated and sensitivity analysis were conducted to
      compare BMDa alone, TBS alone, and the combination of BMDa and TBS. Subgroup
      analyses were performed specifically for women with osteopenia, and for women
      with T-score-defined osteoporosis. RESULTS: Across all subjects (n=42, 126)
      weight and body mass index were greater and BMDa and TBS both less in women with
      fractures. The odds of vertebral fracture were 3.20 (95% CI, 2.01-5.08) for each
      incremental decrease in TBS, 1.95 (1.34-2.84) for BMDa, and 3.62 (2.32-5.65) for
      BMDa + TBS combined. The AUC was greater for TBS than for BMDa (0.746 vs. 0.662,
      p=0.011). At iso-specificity (61.9%) or iso-sensitivity (61.9%) for both BMDa and
      TBS, TBS + BMDa sensitivity or specificity was 19.1% or 16.7% greater than for
      either BMDa or TBS alone. Among subjects with osteoporosis (n=11, 40) both BMDa
      (p=0.0008) and TBS (p=0.0001) were lower in subjects with fractures, and both OR
      and AUC (p=0.013) for BMDa + TBS were greater than for BMDa alone (OR=4.04 [2.35
      6.92] vs. 2.43 [1.49-3.95]; AUC=0.835 [0.755-0.897] vs. 0.718 [0.627-0.797],
      p=0.013). Among subjects with osteopenia, TBS was lower in women with fractures
      (p=0.0296), but BMDa was not (p=0.75). Similarly, the OR for TBS was
      statistically greater than 1.00 (2.82, 1.27-6.26), but not for BMDa (1.12, 0.56
      2.22), as was the AUC (p=0.035), but there was no statistical difference in
      specificity (p=0.357) or sensitivity (p=0.678). CONCLUSIONS: The trabecular bone
      score warrants further study as to whether it has any clinical application in
      osteoporosis detection and the evaluation of fracture risk.

PMID- 19747993
TI  - Intranasal administration of a live non-pathogenic avian H5N1 influenza virus
      from a virus library confers protective immunity against H5N1 highly pathogenic
      avian influenza virus infection in mice: comparison of formulations and
      administration routes of vaccines.
AB  - Outbreaks of highly pathogenic avian influenza viruses (HPAIVs) would cause
      disasters worldwide. Various strategies against HPAIVs are required to control
      damage. It is thought that the use of non-pathogenic avian influenza viruses as
      live vaccines will be effective in an emergency, even though there might be some
      adverse effects, because small amounts of live vaccines will confer immunity to
      protect against HPAIV infection. Therefore, live vaccines have the advantage of
      being able to be distributed worldwide soon after an outbreak. In the present
      study, we found that intranasal administration of a live H5N1 subtype non
      pathogenic virus induced antibody and cytotoxic T lymphocyte responses and
      protected mice against H5N1 HPAIV infection. In addition, it was found that a
      small amount (100 PFU) of the live vaccine was as effective as 100 microg
      (approximately 10(10-11) PFU of virus particles) of the inactivated whole
      particle vaccine in mice. Consequently, the use of live virus vaccines might be
      one strategy for preventing pandemics of HPAIVs in an emergency.

PMID- 19747994
TI  - Vaginal delivery of the recombinant HIV-1 clade-C trimeric gp140 envelope protein
      CN54gp140 within novel rheologically structured vehicles elicits specific immune
      responses.
AB  - Rheologically structured vehicle (RSV) gels were developed as delivery systems
      for vaginal mucosal vaccination with an HIV-1 envelope glycoprotein (CN54gp140).
      RSVs comprised a mucoadhesive matrix-forming and vaginal fluid absorbing polymer.
      The mucoadhesive and rheological properties of the RSVs were evaluated in vitro,
      and the distribution, antigenicity and release of CN54gp140 were analysed by
      ELISA. CN54gp140 was uniformly distributed within the RSVs and continuously
      released in vitro in an antigenically intact form over 24h. Vaginal
      administration to rabbits induced specific serum IgG, and IgG and IgA in genital
      tract secretions. The RSVs are a viable delivery modality for vaginal
      immunization.

PMID- 19747995
TI  - Differentiation of field isolates and vaccine strains of infectious
      laryngotracheitis virus by DNA sequencing.
AB  - Two different regions of the infected cell protein 4 (ICP4) gene of infectious
      laryngotracheitis virus (ILTV) were amplified and sequenced for characterization
      of field isolates and tissue culture-origin (TCO) and chicken embryo-origin (CEO)
      vaccine strains. Phylogenetic analysis of the two regions showed differences in
      nucleotide and amino acid sequences between field isolates and attenuated
      vaccines. The PCR-RFLP results were identical to those obtained by DNA sequencing
      and validated their use to differentiate ILTV strains. The approach using the
      sequencing of the two fragments of the ICP4 gene showed to be an efficient and
      practical procedure to differentiate between field isolates and vaccine strains
      of ILTV.

PMID- 19747996
TI  - Antibiotic resistance free plasmid DNA expressing LACK protein leads towards a
      protective Th1 response against Leishmania infantum infection.
AB  - Canine visceral leishmaniasis is a serious public health concern in the
      Mediterranean basin since dogs are the main Leishmania infantum reservoir.
      However, there is not a vaccination method in veterinary use in this area, and
      therefore the development of a vaccine against this parasite is essential for the
      possible control of the disease. Previous reports have shown the efficacy of
      heterologous prime-boost vaccination with the pCIneo plasmid and the poxvirus VV
      (both Western Reserve and MVA strains) expressing L. infantum LACK antigen
      against canine leishmaniasis. As pCIneo-LACK plasmid contains antibiotic
      resistance genes, its use as a profilactic method is not recommended. Hence, the
      antibiotic resistance gene free pORT-LACK plasmid is a more suitable tool for its
      use as a vaccine. Here we report the protective and immunostimulatory effect of
      the prime-boost pORT-LACK/MVA-LACK vaccination tested in a canine experimental
      model. Vaccination induced a reduction in clinical signs and in parasite burden
      in the liver, an induction of the Leishmania-specific T cell activation, as well
      as an increase of the expression of Th1 type cytokines in PBMC and target organs.

PMID- 19747997
TI  - Factors associated with hallux valgus in a population-based study of older women
      and men: the MOBILIZE Boston Study.
AB  - OBJECTIVE: To examine potential risk factors for hallux valgus in community
      dwelling elders. METHOD: Data from 600 MOBILIZE Boston Study participants (386
      women and 214 men) were analyzed. Hallux valgus was defined as >15 degrees
      angular deviation of the hallux with respect to the first metatarsal bone toward
      the lesser toes. Associations of hallux valgus with age, body mass index (BMI),
      race, education, pes planus, foot pain, and in women, history of high heel shoe
      use, were assessed using sex-specific Poisson regression with robust variance
      estimation for risk ratios (RR) and 95% confidence intervals (CI). RESULTS:
      Hallux valgus was present in 58% of women and 25% of men. Higher BMI was
      inversely associated with presence of hallux valgus in women (P trend=0.001),
      with the strongest inverse association observed in those with BMI of 30.0 or more
      compared to those with normal BMI (RR=0.7, 95% CI: 0.5, 0.9). Women, who usually
      wore high-heeled shoes during ages 20-64 years compared to those who did not, had
      increased likelihood of hallux valgus (RR=1.2, 95% CI: 1.0, 1.5). Among men,
      those with BMI between 25.0 and 29.9 had increased likelihood of hallux valgus
      compared to those with normal BMI (RR=1.9, 95% CI: 1.0, 3.5). Men with pes planus
      were more likely to have hallux valgus (RR=2.1, 95% CI: 1.3, 3.3) compared to men
      without pes planus. CONCLUSION: In women, hallux valgus was associated with lower
      BMI and high heel use during ages 20-64, while in men, associations were observed
      with higher BMI and pes planus. Our results suggest that the etiologic mechanisms
      for hallux valgus may differ between men and women.

PMID- 19747998
TI  - Deficiency of tenascin-C delays articular cartilage repair in mice.
AB  - OBJECTIVE: In human articular cartilage, tenascin-C (TN-C) expression decreases
      during maturation of chondrocytes, and almost disappears in adults; however, it
      reappears in damaged cartilage. To examine the effects of TN-C on cartilage
      degeneration and repair, we compared articular cartilage degeneration between
      wild-type (WT) and tenascin-C knockout mouse (TNKO) mice using a spontaneous
      osteoarthritis (OA) in aged joints and surgical OA model. In addition, we made
      full-thickness cartilage defects and compared the cartilage repair process
      between the two groups. METHODS: The surgical procedure to create degenerative OA
      model was performed by transecting the anterior cruciate ligament and medial
      collateral ligament. Full-thickness defects were created in the center of the
      femoral trochlea to evaluate cartilage repair. Sections of cartilage were stained
      with hematoxylin and eosin or safranin-O, and immunostaining for TN-C. The
      degrees of degeneration and repair were graded. RESULTS: In the WT surgical OA
      model, the articular cartilage was almost normal at 2 weeks, but safranin-O
      decreased staining at 4 weeks. In TNKO mice, safranin-O decreased staining at 2
      weeks, and cartilage was injured intensely at 4 weeks. In the cartilage repair
      model, TN-C was expressed after 1 week, was strongly expressed in the upper layer
      of regenerated tissue after 3 weeks, and disappeared after 6 weeks. The defects
      were restored until 6 weeks in WT mice; however, defects in TNKO mice were filled
      with fibrous tissue with no cartilage-like tissue. CONCLUSIONS: This study
      revealed that cartilage repair in TNKO mice was significantly slower than that in
      WT mice and that the deficiency of TN-C progressed during cartilage degeneration.

PMID- 19747999
TI  - Incidental findings in "normal" volunteers.

PMID- 19748000
TI  - Hip arthroplasty. Part 1: prosthesis terminology and classification.
AB  - Hip arthroplasty is an extremely common orthopaedic procedure and there is a wide
      array of implants that are in current use in the UK. The follow-up of patients
      who have undergone insertion of a hip prosthesis is shifting from a consultant
      lead hospital service towards primary care. As this change in patient care
      continues it becomes increasingly important that an accurate description of the
      radiographic features is communicated to the primary-care practitioner so
      appropriate specialist input can be triggered. This review focuses on the
      terminology and classification of hip prostheses. This acts as a precursor for
      Part 2 of this series, which describes the normal and abnormal radiographic
      findings following hip prosthesis insertion.

PMID- 19748001
TI  - Hip arthroplasty. Part 2: normal and abnormal radiographic findings.
AB  - This review addresses the normal and abnormal radiographic findings that can be
      encountered during the follow-up of patients with total hip arthroplasty (THA).
      The relative significance of different patterns of radiolucency, bone sclerosis,
      and component position is discussed. The normal or pathological significance of
      these findings is correlated with design, surface, and fixation of the prosthetic
      components. It is essential to have a good knowledge of expected and unexpected
      radiological evolution according to the different types of prostheses. This paper
      emphasizes the importance of serial studies compared with early postoperative
      radiographs during follow-up in order to report accurately any sign of prosthetic
      failure and trigger prompt specialist referral. Basic technical guidelines and
      schedule recommendations for radiological follow-up are summarized.

PMID- 19748002
TI  - Computer-aided detection (CAD) as a second reader using perspective filet view at
      CT colonography: effect on performance of inexperienced readers.
AB  - AIM: To evaluate whether computer-aided detection (CAD) as a second reader using
      perspective filet view [three-dimensional (3D) filet] improves the performance of
      inexperienced readers at computed tomography colonography (CTC) compared with
      unassisted 3D filet and unassisted two-dimensional (2D) CTC. MATERIAL AND
      METHODS: Fifty symptomatic patients underwent CTC and same-day colonoscopy with
      segmental unblinding. Two inexperienced readers read the CTC studies on 3D filet
      and 2D several weeks apart. Four months later, readers re-read the cases only
      evaluating CAD marks using 3D filet. Suspicious CAD marks not previously
      described on 3D filet were recorded. Jackknife free-response receiver operating
      characteristic (JAFROC-1) analysis was used to compare the observers'
      performances in detecting lesions with 3D filet, 2D and 3D filet with CAD.
      RESULTS: One hundred and three lesions > or =3mm were detected at colonoscopy
      with segmental unblinding. CAD alone had a sensitivity of 73% (75/103) at a mean
      false-positive rate per patient of 12.8 in supine and 11.4 in prone. For
      inexperienced readers sensitivities with 3D filet with CAD were 58% (60/103) and
      48% (50/103) with an improvement of 14-16 percentage points (p<0.05) compared
      with 2D and of 10-11 percentage points (p<0.05) compared with 3D filet. For
      inexperienced readers, the false-positive rate was 25-41% and 71-200% higher with
      3D filet with CAD compared with 3D filet and 2D, respectively. JAFROC-1 analysis
      showed no significant differences in per-lesion overall performance among reading
      modes (p=0.8). CONCLUSION: CAD applied as a second reader using 3D filet
      increased both sensitivity and the number of false positives by inexperienced
      readers compared with 3D filet and 2D, thus not improving overall performance,
      i.e., the ability to distinguish between lesions and non-lesions.

PMID- 19748003
TI  - The impact of European research ethics legislation on UK radiology research
      activity: a bibliometric analysis.
AB  - AIM: To determine whether there is evidence of a reduction in radiology research
      activity in the UK following the implementation of the European research ethics
      legislation, which came in to force in 2001 and has been widely criticised as an
      impediment to research. MATERIALS AND METHODS: A bibliometric analysis was
      performed by searching PubMed for all first-author publications from UK
      departments of "radiology" or "medical imaging" between 1995 and 2007. Results
      were sub-categorized into those papers published in the highest cited general
      radiology journals and by publication type: original research, reviews, and case
      reports. RESULTS: From 1995 to 2007 the total number of publications rose by 6.5%
      from 137 to 146 with the increase occurring in non-general radiology journals.
      Original articles fell from 18 in 1995 to 12 in 2003, but then rose to 24 by 2007
      (33% rise). This dip was paralleled by a fall and then recovery in case report
      publications. The most dramatic change has been in the number of review articles,
      which has increased more than eightfold from seven in 1995 to 65 in 2007 to
      become the most common form of publication. CONCLUSION: The overall number of
      original scientific articles, published by first-author UK radiologists, has
      increased slightly over the last 12 years despite a temporary fall associated
      with the introduction of new research ethics legislation.

PMID- 19748004
TI  - Radiology errors: are we learning from our mistakes?
AB  - AIM: To question practising radiologists and radiology trainees at a large
      international meeting in an attempt to survey individuals about error reporting.
      MATERIALS AND METHODS: Radiologists attending the 2007 Radiological Society of
      North America (RSNA) annual meeting were approached to fill in a written
      questionnaire. Participants were questioned as to their grade, country in which
      they practised, and subspecialty interest. They were asked whether they kept a
      personal log of their errors (with an error defined as "a mistake that has
      management implications for the patient"), how many errors they had made in the
      preceding 12 months, and the types of errors that had occurred. They were also
      asked whether their local department held regular discrepancy/errors meetings,
      how many they had attended in the preceding 12 months, and the perceived
      atmosphere at these meetings (on a qualitative scale). RESULTS: A total of 301
      radiologists with a wide range of specialty interests from 32 countries agreed to
      take part. One hundred and sixty-six of 301 (55%) of responders were
      consultant/attending grade. One hundred and thirty-five of 301 (45%) were
      residents/fellows. Fifty-nine of 301 (20%) of responders kept a personal record
      of their errors. The number of errors made per person per year ranged from none
      (2%) to 16 or more (7%). The majority (91%) reported making between one and 15
      errors/year. Overcalls (40%), under-calls (25%), and interpretation error (15%)
      were the predominant error types. One hundred and seventy-eight of 301 (59%) of
      participants stated that their department held regular errors meeting. One
      hundred and twenty-seven of 301 (42%) had attended three or more meetings in the
      preceding year. The majority (55%) who had attended errors meetings described the
      atmosphere as "educational." Only a small minority (2%) described the atmosphere
      as "poor" meaning non-educational and/or blameful. CONCLUSION: Despite the
      undeniable importance of learning from errors, many radiologists and institutions
      do not engage in such practice. Radiologists and radiology departments must
      continue to improve the process of recording and addressing errors.

PMID- 19748005
TI  - Kimura's disease: imaging patterns on computed tomography.
AB  - AIM: To define the role of computed tomography (CT) in identifying and
      classifying the imaging patterns of diagnostic value in Kimura's disease of the
      head and neck. METHODS: A retrospective study was undertaken comprising 13
      patients with histopathological evidence of Kimura's disease. The patients'
      clinical and pathological records were reviewed against a detailed analysis of
      their CT images performed from the base of the skull to the arch of the aorta.
      RESULTS: Both well-defined, nodular masses, as well as ill-defined plaque-like
      infiltrative masses were seen in the subcutaneous tissue of the head and neck
      region. All patients had lesions adjacent to the major salivary glands. The
      parotid gland was affected in 10 of the 13 cases and the submandibular gland was
      affected in the rest. Contrast enhancement was variable. More than half of the
      cases had associated lymphadenopathy. Some of them showed atrophy of the skin and
      subcutaneous fat overlying the subcutaneous masses. Blood eosinophilia was a
      consistent feature in all the cases. CONCLUSION: The patterns of distribution,
      morphology, and enhancement of the lesions in Kimura's disease that can be
      demonstrated at CT, enables a confident, non-invasive diagnosis of this
      condition, in an appropriate clinical context.

PMID- 19748006
TI  - Prospective comparison of 3D FIESTA versus fat-suppressed 3D SPGR MRI in
      evaluating knee cartilage lesions.
AB  - AIM: To prospectively compare the accuracy of three-dimensional fast imaging
      employing steady-state acquisition (3D FIESTA) sequences with that of fat
      suppressed three-dimensional spoiled gradient-recalled (3D SPGR) in the diagnosis
      of knee articular cartilage lesions, using arthroscopy as the reference standard.
      MATERIALS AND METHODS: Fifty-eight knees in 54 patients (age range 21-82 years;
      mean 36 years) were prospectively evaluated by using sagittal 3D FIESTA and
      sagittal fat-suppressed 3D SPGR sequences. Articular cartilage lesions were
      graded on MRI and during arthroscopy with a modified Noyes scoring system.
      Sensitivity, specificity, and accuracy were assessed. Interobserver agreement was
      determined with kappa statistics. RESULTS: The performance of 3D FIESTA sequences
      (sensitivity, specificity, and accuracy were 80, 94, and 92%, respectively, for
      reader 1 and 76, 94, and 90%, respectively, for reader 2) was similar to that of
      fat-suppressed 3D SPGR sequences (sensitivity, specificity, and accuracy were 82,
      92, and 90%, respectively, for reader 1 and 82, 90, and 88%, respectively, for
      reader 2) in the detection of knee articular cartilage lesions. The interobserver
      agreement varied from fair to good to excellent (kappa values from 0.43-0.83).
      CONCLUSION: 3D FIESTA has good diagnostic performance, comparable with fat
      suppressed 3D SPGR in evaluating knee cartilage lesions, and it can be
      incorporated into routine knee MRI protocols due to the short acquisition time.

PMID- 19748007
TI  - Needle placement accuracy during stereotactic localization mammography.
AB  - AIM: To derive a mathematical model to describe the relationship between lesion
      position in the breast and measurements derived from the stereoradiographs to
      enable more accurate sampling of a lesion during stereotactic mammographic needle
      placement. MATERIALS AND METHODS: The affect that registration errors have on the
      accuracy of needle placement when identifying the lesion on the stereoradiographs
      was investigated using the mathematical model. RESULTS: The focus-to-film
      distance of the x-ray tube and the horizontal distance of the lesion from the
      centre of rotation have little effect on error. Registration errors for lesions
      lying at a greater perpendicular distance in the breast from the centre of
      rotation produce smaller localization errors when compared with lesions sited
      closer. Lesion registration errors during marking of the stereoradiographs are
      exacerbated by decreasing the angle of x-ray tube swing. CONCLUSIONS: When
      problems are encountered in making an accurate registration of the lesion on the
      stereoradiographs, consider the following error reducing strategies: (1) employ
      an approach that places the lesion the maximum distance away from the film
      cassette; (2) avoid reducing the angle of tube swing; and (3) consider sampling
      superficial and deep to, as well as at, the location indicated. The possibility
      of erroneous tissue sampling should be borne in mind when reviewing the pathology
      report.

PMID- 19748008
TI  - Imaging of paediatric liver tumours with pathological correlation.
AB  - Paediatric hepatic tumours are relatively rare with malignant lesions being twice
      as frequent as benign neoplasms and are mostly metastases. Imaging has a
      significant role in the evaluation of most paediatric liver tumours.
      Differentiating benign from malignant tumours is important as it significantly
      affects treatment decisions. We present the characteristic radiological and
      pathological features of the most common paediatric liver tumours.

PMID- 19748009
TI  - MR enterography in the evaluation of small bowel dilation.
AB  - Magnetic reasonance (MR) enterography enables high contrast resolution depiction
      of the location and cause of bowel obstruction through a combination of
      predictable luminal distension and multiplanar imaging capabilities. Furthermore,
      because the patient is not exposed to ionizing radiation, sequential "dynamic" MR
      imaging can be performed repeatedly over time further facilitating depiction of
      the site and/or the cause of obstruction. With increasing availability of MR
      imaging and standardization of the oral contrast medium regimens, it is likely
      that this technique will assume an ever-increasing role in the evaluation of
      small bowel dilation in the coming years. We illustrate the utility of MR
      enterography in the evaluation of small bowel dilation, whether it be mechanical,
      functional (e.g., ileus), or related to infiltrative mural disease.

PMID- 19748010
TI  - Invasive uraemic calcinosis of the hip.

PMID- 19748011
TI  - CT-guided sacroplasty for the treatment of zone II sacral insufficiency
      fractures.

PMID- 19748012
TI  - RE: Incidental breast masses detected by computed tomography: are any imaging
      features predictive of malignancy?

PMID- 19748013
TI  - RE: Magnetic resonance spectroscopy of the brain: review of metabolites and
      clinical applications.

PMID- 19748014
TI  - Data and, now, action.

PMID- 19748015
TI  - Safe practice, safe care.

PMID- 19748018
TI  - Are pediatric ED nurses delivering tobacco cessation advice to parents?
AB  - INTRODUCTION: Due to the adverse health effects of environmental tobacco smoke
      exposure in children, pediatric registered nurses (RNs) have frequent encounters
      with parents who smoke. RNs have a unique opportunity to provide tobacco
      cessation counseling to parental smokers during their child's ED or hospital
      visit. The purpose of this study was to assess pediatric RNs' levels of
      knowledge, attitudes, and behaviors regarding provision of tobacco cessation
      advice to parents who smoke. METHODS: An anonymous electronic self-administered
      survey of current tobacco cessation practices and attitudes was sent to ED RNs (N
      = 130) at a tertiary care pediatric hospital in Ohio. RESULTS: A total of 87 RNs
      (67%) completed the survey. Approximately 22% of respondents indicated that they
      assess parental smoking status, 14% encouraged parents who smoke to quit, and
      even fewer indicated that they provided specific counseling or assistance to
      their patients' parents. Perceived barriers to delivering tobacco cessation
      counseling included parent resistance, parent complaints, parent anger, and lack
      of parent materials. More than 60% of respondents agreed that they should learn
      new ways to help parents quit and advise parents who use tobacco to quit and that
      RNs can be effective in helping parents quit. DISCUSSION: Pediatric ED nurses are
      unlikely to engage in tobacco cessation activities but express interest in
      learning new ways to help patients' parents quit smoking. Future education could
      promote tobacco cessation advice and assistance, thus improving the health of
      parents and patients in the pediatric setting.

PMID- 19748019
TI  - Nurse-patient/visitor communication in the emergency department.
AB  - Patients and visitors need to be encouraged to express their needs and be
      provided with enough relevant information so that treatment and recovery from
      illness are optimized. In the emergency department, it is important for nurses to
      create an environment of trust, respect, and acceptance. Using a survey design, a
      convenience sample of nurses and patients/visitors described patient/visitor
      communication needs and determined if needs were met during the ED encounter.
      Data were analyzed using descriptive statistics. Mantel Haenszel chi(2) tests
      were used to determine associations between patient-rated importance of nurse
      communication needs and nursing communication performance. Sixty-four nurses and
      123 patients/visitors completed a communication needs survey. More than 80% of
      patients answered "excellent" or "very good" to 6 of the top 10 important
      communication needs. Patient and nurse importance differed significantly on only
      2 communication needs: calm voice and social status (nurses rated these needs of
      higher importance than patients; P = .01, P = .006). Patient-ranked importance
      was positively associated with patient opinion of how well needs were met in 6 of
      19 patient/visitor communication needs; that is, not making assumptions about
      social status (P = .0006), offering reassurance to calm fears (P = .004), and
      teaching about primary medical concerns/conditions (P = .01). Nurse and
      patient/visitor perceptions of important communication are similar. Educating
      nurses about patient/visitor communication needs is the first step in enhancing
      how well nurses meet those needs.

PMID- 19748020
TI  - Childhood asthma: ED follow-up determinants.
AB  - INTRODUCTION: This comparative correlational study investigated families who use
      the emergency department for childhood asthma to identify determinants of follow
      up care. The primary hypothesis was: families who obtain follow-up care differ in
      predisposing, enabling, and need characteristics from families who do not obtain
      follow-up care. METHOD: A convenience sample of 63 children presenting to the
      pediatric emergency department of a Central Florida hospital were enrolled.
      Logistic regression techniques were utilized to explicate the individual and
      combined effects of the variables that best predicted the outcome variable. The
      dichotomous dependent variable was follow-up care within 30 days of the ED visit.
      RESULTS: Sixty-seven percent of the children did not follow up as directed.
      Mother's level of education was significantly associated with no follow-up (P =
      .0282). Odds of no follow-up were higher for children with more severe asthma
      (odds ratio [OR] 12.44) or older mothers (OR 2.14). DISCUSSION: Follow-up is not
      occurring at desired levels. Although this study has clinical and research
      implications for health care providers, further research is needed to identify
      follow-up determinants and develop interventions to improve follow-up rates and
      asthma outcomes.

PMID- 19748021
TI  - Difficult venous access in children: taking control.

PMID- 19748022
TI  - Intraosseous vascular use at signature healthcare Brockton hospital department of
      emergency services.

PMID- 19748023
TI  - Guesting area: an alternative for boarding mental health patients seen in
      emergency departments.

PMID- 19748024
TI  - Special considerations in working with gastric bypass patients for the emergency
      nurse.

PMID- 19748025
TI  - Evaluation and management of hereditary hemophilia in the emergency department.

PMID- 19748026
TI  - A healthy 47-year-old man dies of group A Streptococcus.

PMID- 19748028
TI  - The increasing geriatric population and overcrowding in the emergency department:
      one hospital's approach.

PMID- 19748029
TI  - Enhancing the reporting of "near miss" events in a children's emergency
      department.

PMID- 19748030
TI  - Incorporating the Beers criteria may reduce ED visits in elderly persons.

PMID- 19748031
TI  - 2008 ENA National Scorecard on State Roadway Laws: A blueprint for injury
      prevention.

PMID- 19748032
TI  - Clinical practice guidelines: key resources to guide clinical decision making and
      enhance quality health care.

PMID- 19748033
TI  - Planning an evidence-based and fundable injury-prevention program.

PMID- 19748034
TI  - Mortars and rockets.

PMID- 19748037
TI  - Assessing competency with the use of human patient simulation in the emergency
      department.

PMID- 19748038
TI  - Pediatric genitourinary emergencies in the emergency department.

PMID- 19748039
TI  - Drug- and toxin-induced Rhabdomyolysis.

PMID- 19748040
TI  - Unexplained car crash: what you should consider.

PMID- 19748041
TI  - From triage to treatment of severe abdominal pain in the emergency department:
      evaluating the implementation of the emergency severity index.

PMID- 19748042
TI  - Locked-in syndrome in children: report of five cases and review of the
      literature.
AB  - The locked-in syndrome is a rare neurologic disorder defined by (1) the presence
      of sustained eye opening; (2) preserved awareness; (3) aphonia or hypophonia; (4)
      quadriplegia or quadriparesis; and (5) a primary mode of communication that uses
      vertical or lateral eye movement or blinking. Five cases are reported here, and
      previous literature is reviewed. According to the literature, the most common
      etiology of locked-in syndrome in children is ventral pontine stroke, most
      frequently caused by a vertebrobasilar artery thrombosis or occlusion. In terms
      of prognosis, 35% of pediatric locked-in syndrome patients experienced some motor
      recovery, 26% had good recovery, 23% died, and 16% remained quadriplegic and
      anarthric. These findings raise important ethical considerations in terms of
      quality of life and end-of-life decisions in such challenging cases.

PMID- 19748043
TI  - Methylenetetrahydrofolate reductase gene polymorphism and childhood stroke.
AB  - Genotyping for the methylenetetrahydrofolate reductase gene (MTHFR) has been
      recommended for part of the evaluation for underlying prothrombotic state in
      childhood stroke; however, studies are inconclusive regarding the role of this
      gene and also the role of hyperhomocysteinemia, which is the putative mechanism
      by which MTHFR polymorphism is related to stroke. The prevalence of MTHFR
      polymorphism in childhood arterial ischemic stroke and cerebral sinovenous
      thrombosis was compared with that of a reference population, and prevalence of
      hyperhomocysteinemia was reviewed. In arterial ischemic stroke, the prevalence of
      at-risk methylenetetrahydrofolate reductase genotypes was 27%, and in cerebral
      sinovenous thrombosis it was 13%; the population prevalence was 26%. The odds
      ratio for at-risk genotype in childhood arterial ischemic stroke was 1.06 (95%
      confidence interval, 0.22-4.0); in cerebral sinovenous thrombosis, it was 0.42
      (95% confidence interval, 0.01-3.6). No tested cases had hyperhomocysteinemia.
      MTHFR polymorphism and hyperhomocysteinemia were not risk factors in childhood
      arterial ischemic stroke or cerebral sinovenous thrombosis in the Intermountain
      West region.

PMID- 19748044
TI  - Neurodevelopment of children under 3 years of age with Smith-Magenis syndrome.
AB  - Systematic data regarding early neurodevelopmental functioning in Smith-Magenis
      syndrome are limited. Eleven children with Smith-Magenis syndrome less than 3
      years of age (mean, 19 months; range, 5-34 months) received prospective
      multidisciplinary assessments using standardized measures. The total sample
      scored in the moderately to severely delayed range in cognitive functioning,
      expressive language, and motor skills and exhibited generalized hypotonia, oral
      motor abnormalities, and middle ear dysfunction. Socialization skills were
      average, and significantly higher than daily living, communication, and motor
      abilities, which were below average. Mean behavior ratings were in the
      nonautistic range. According to exploratory analyses, the toddler subgroup scored
      significantly lower than the infant subgroup in cognition, expressive language,
      and adaptive behavior, suggesting that the toddlers were more delayed than the
      infants relative to their respective peers. Infants aged approximately 1 year or
      younger exhibited cognitive, language, and motor skills that ranged from average
      to delayed, but with age-appropriate social skills and minimal maladaptive
      behaviors. At ages 2 to 3 years, the toddlers consistently exhibited cognitive,
      expressive language, adaptive behavior, and motor delays and mildly to moderately
      autistic behaviors. Combining age groups in studies may mask developmental and
      behavioral differences. Increased knowledge of these early neurodevelopmental
      characteristics should facilitate diagnosis and appropriate intervention.

PMID- 19748045
TI  - Lactic dehydrogenase isoenzymes in adolescents with multiple sclerosis.
AB  - Multiple sclerosis is an immune-mediated demyelinating disease with high
      morbidity and major mortality. To determine the potential use of lactic
      dehydrogenase activity and lactic dehydrogenase isoenzyme concentrations in
      cerebrospinal fluid as biomarkers of multiple sclerosis, we reviewed the files of
      all patients with multiple sclerosis who attended our tertiary pediatric medical
      facility from 1999-2005. The study group included three adolescent patients with
      multiple sclerosis (cerebrospinal fluid analysis at diagnosis) and one patient
      with recurrent optic neuritis (cerebrospinal fluid analysis during a disease
      episode). The isoenzyme pattern was abnormal in all patients with multiple
      sclerosis, with higher-than-normal levels of lactic dehydrogenase-2, lactic
      dehydrogenase-3, and lactic dehydrogenase-5 in two patients, and lower-than
      normal levels of lactic dehydrogenase-4 in one patient. It was not necessarily,
      however, the same two patients who had the abnormally high levels of lactic
      dehydrogenase-2, -3, and -5. The patient with optic neuritis also exhibited an
      abnormal lactic dehydrogenase isoenzyme pattern that shared common features with
      the others. Multiple sclerosis appears to be characterized by an abnormal lactic
      dehydrogenase isoenzyme pattern in cerebrospinal fluid. The importance of this
      finding and its diagnostic potential use warrant further investigation.

PMID- 19748046
TI  - Meta-analysis of apparent diffusion coefficients in the newborn brain.
AB  - Diffusion-weighted imaging and its quantitative apparent diffusion coefficient
      can assess severity in newborn hypoxic-ischemic injuries. A meta-analysis
      established normative values in term newborns, in comparison to those values in
      hypoxic-ischemic newborns with good versus poor outcomes. Measurements from 14
      reports were stratified into three levels of increasing specificity: tissue type
      (gray matter, white matter, or cerebellum), tissue distribution (e.g., cortex or
      white-matter tracts), and anatomic structures (e.g., frontal white matter or
      posterior limb of the internal capsule). Normative apparent diffusion
      coefficients constituted white matter > gray matter = cerebellum, with lowest
      values in the posterior limb of the internal capsule and thalamus, and the
      highest in frontal and occipital white matter. Differences between normative and
      hypoxic-ischemic injury good-outcome groups were not evident. Values in the poor
      outcome group were significantly lower than normative data in white matter, gray
      matter, cortical gray matter, white matter tracts, posterior limb of the internal
      capsule, and cortical, frontal, and occipital white matter. Comparisons between
      injury groups found that coefficients were only significantly lower in the
      occipital cortex among poor outcomes. Coefficient values were lower in deep brain
      compared with cortical structures, reflecting tissue maturation and myelination.
      Differences between normative and hypoxic-ischemic injury poor-outcome groups
      suggest pathologies associated with neurologic sequelae. This meta-analysis
      provides the basis for normative apparent diffusion coefficient values in the
      newborn brain.

PMID- 19748047
TI  - Developmental dilatation of Virchow-Robin spaces: a genetic disorder?
AB  - In childhood, widening of Virchow-Robin spaces is rarely secondary to specific
      progressive disorders, but more often appears in poorly characterized
      developmental conditions. From data collected in a neuropediatric department, we
      examined whether clinical data associated with "constitutional widening of
      Virchow-Robin spaces" allowed delineation of recognizable entities. Signs in 10
      patients, mostly boys, suggested nonspecific cerebral dysfunctions, e.g.,
      developmental delay, nonspecific epilepsy, headaches, or benign macrocephaly.
      Spaces were sometimes round, subsequently mimicking microcystic malacic lesions.
      In two patients, abnormal magnetic resonance imaging signals were evident in
      white matter contiguous to widened perivascular spaces, suggesting a broader
      disorder of fluid exchanges. Four cases occurred in two sibships. In two
      families, other patients exhibited early developmental difficulties. Long-term
      clinical and magnetic resonance imaging surveillance will clarify which cases of
      primary Virchow-Robin space dilatation imply a benign prognosis. Performance of
      magnetic resonance imaging on any relative exhibiting minor neuropsychologic
      handicaps would permit estimations of real genetic incidence.

PMID- 19748048
TI  - Prophylactic drugs and cytokine and leptin levels in children with migraine.
AB  - The study objective was to evaluate levels of the cytokines tumor necrosis factor
      alpha, interleukin-1beta, and interleukin-6 and of leptin, and then to determine
      the relationship between these levels and clinical responses in children with
      migraine after prophylactic therapy with one of four drugs. In all, 77 children
      who needed prophylactic drugs were treated with cyproheptadine, amitriptyline,
      propranolol, or flunarizine. Serum levels of the cytokines and leptin were
      measured before and 4 months after the treatment. Results were compared by drug
      for headache frequency, severity, and duration, the PedMIDAS score, and levels of
      each cytokine and of leptin. Each of the four drugs not only decreased the
      frequency and duration but also the severity of headache, and the PedMIDAS score.
      None of the drugs was found to be superior to others in terms of reduction in
      cytokine levels (P > 0.05). Both cyproheptadine and flunarizine (but not
      amitriptyline and propranolol) caused an increase in leptin levels (P < 0.05).
      These data suggest that cytokine levels are related to clinical responses, and
      might help in objective evaluation of clinical response in migraine. To our
      knowledge, the present study is the first trial to compare the effects of
      prophylactic drugs, cytokine levels, and leptin levels in children with migraine.

PMID- 19748049
TI  - Childhood serum anti-fetal brain antibodies do not predict autism.
AB  - Autoimmune hypotheses for autism include in utero transplacental exposure to
      maternal antibodies and acquired postnatal insults. Previous work demonstrated
      that some mothers of children with autistic disorder have specific antibodies
      against human fetal brain that differentiate them from mothers with typical
      children. In the present study, Western immunoblotting was used to determine
      whether children with autistic spectrum disorders (n = 29) have serum reactivity
      against human fetal brain that differs from that of controls (n = 14). There was
      no significant difference in reactivity, corrected for serum immunoglobulin G
      content and brain actin content and with special attention to reactive bands at
      36, 39, 61, and 73 kDa, between autistic children and normal control subjects.
      Thus, in contrast to mothers, antibody reactivity against human fetal brain as
      measured in children ages 3-12 years does not appear to be a useful biomarker for
      autism.

PMID- 19748050
TI  - Fetal intracerebral hemorrhage in familial thrombophilia.
AB  - We describe a fetal intracerebral hemorrhage associated with familial
      thrombophilia. Intraventricular and intraparenchymal hemorrhage of the left
      cerebral hemisphere was diagnosed at 22 weeks of gestation. Neuropathologic
      examination demonstrated a large germinal zone hemorrhage and ischemic changes
      secondary to bleeding. The fetus manifested a heterozygous Leiden mutation of the
      factor V gene, and a heterozygous F76L mutation of the protein C gene. The
      literature indicates that the coexistence of genetic risk factors of
      thrombophilia and fetal intracerebral hemorrhage is rare, except in the context
      of pregnancy-related complications. The utility of laboratory screening is
      discussed.

PMID- 19748051
TI  - Herpes simplex virus type-1 encephalitis and occipital ischemic stroke.
AB  - Childhood ischemic stroke is a rare complication of herpes simplex virus type-1
      encephalitis. We describe a previously healthy 3-year-old girl who presented with
      bilateral occipital ischemic stroke, attributable to herpes simplex virus type-1
      encephalitis, highlighting the importance of viral diagnostics in cerebrospinal
      fluid.

PMID- 19748052
TI  - Late infantile neuronal ceroid lipofuscinosis: a new mutation in Arabs.
AB  - The neuronal ceroid lipofuscinoses are a group of dominant neurodegenerative,
      progressive, and fatal disorders characterized clinically by myoclonic epilepsy,
      in variable association with dementia, ataxia, and visual loss. Neuronal ceroid
      lipofuscinoses were classified into several phenotypes according to their age of
      onset: infantile, late infantile, juvenile, and adult. A specific phenotype was
      named "northern epilepsy," and its onset of signs occurs between ages 5-10 years.
      Deficiencies in the lysosomal activity of two specific enzymes were found in
      several types of neuronal ceroid lipofuscinosis: palmitoyl-protein thioesterase
      1, encoded by the CLN1 gene, and tripeptidyl-peptidase 1, encoded by the CLN2
      gene. Several mutations in CLN2 were described previously. We describe a novel
      mutation in two siblings of Israeli-Arab origin, with a clinical picture
      compatible with late infantile neuronal ceroid lipofuscinosis. Both siblings were
      found to be homozygous for a deletion of a C nucleotide at position 775 in exon 7
      of the CLN2 gene. These findings have implications for the worldwide epidemiology
      of neuronal ceroid lipofuscinosis.

PMID- 19748053
TI  - Hashimoto encephalopathy in a 15-year-old-girl: EEG findings and follow-up.
AB  - Hashimoto encephalopathy is characterized by severe neuropsychiatric findings,
      including psychosis, confusion, seizures, stupor, stroke-like episodes, tremor,
      and myoclonus. The combination of findings is variable. Hashimoto encephalopathy
      constitutes an important differential diagnosis in patients with encephalopathy.
      The triad of encephalopathy, corresponding electroencephalographic slowing, and
      increased protein content in cerebrospinal fluid should prompt testing of anti
      thyroid antibodies in blood and cerebrospinal fluid. Elevated antibody levels
      support the diagnosis. We describe a 15-year-old girl with a fluctuating course
      of Hashimoto encephalopathy. Electroencephalograms revealed no specific
      alterations, but widespread slowing of the background activity occurred during
      two episodes of fluctuating encephalopathy. Cortical edema was indicated by
      cranial magnetic resonance imaging during the first episode of encephalopathy, in
      the context of cerebral seizures. Laboratory findings were in accordance with
      Hashimoto encephalopathy, which was steroid-responsive.

PMID- 19748054
TI  - Effect of oral curcumin on Dejerine-Sottas disease.
AB  - Curcumin is the newest therapeutic agent for ameliorating the clinical and
      neuropathologic phenotype of a mouse model of Dejerine-Sottas disease. We
      undertook a 12-month dose-escalation safety trial of oral curcumin in a 15-year
      old Caucasian girl with Dejerine-Sottas disease (point mutation, Ser72Leu)
      complicated by severe weakness, scoliosis, and respiratory impairment. The
      patient received 50 mg/kg/day oral curcumin for the first 4 months and 75
      mg/kg/day thereafter, to complete a 12-month trial. Outcome measures included
      muscle strength, pulmonary function, upper/lower extremity disability,
      neurophysiologic studies, and health-related quality of life. After 12 months,
      the patient experienced no adverse events, and reported good compliance. There
      was little improvement in objective outcome measures. Knee flexion and foot
      strength increased slightly, but hand and elbow strength decreased. Pulmonary
      function, hand function, and measures of upper/lower extremity disability were
      stable or reduced. Her neurophysiologic findings were unchanged. Parent-reported
      quality of life improved for most domains, especially self-esteem, during the 12
      months of treatment. Child-reported quality of life, assessed at the final visit,
      mirrored these results, with overall feelings of happiness and contentment.
      Further studies are required to explore the efficacy and safety of curcumin for
      severe demyelinating neuropathies of infancy and early childhood.

PMID- 19748055
TI  - Diffusion-weighted imaging in preclinical Leigh syndrome.
AB  - We report on a preterm Japanese male baby with Leigh syndrome, i.e., intrauterine
      growth restriction, central apnea, and feeding difficulty. These signs improved
      at 41 weeks of corrected age. At that time, brain magnetic resonance imaging
      revealed increased signal in diffusion-weighted imaging in the parietal white
      matter, bilaterally and symmetrically not respecting vascular territory or
      boundaries. However, clinical improvement deterred us from further investigation.
      About 3 months later, he manifested frequent ictal apnea with myoclonic seizures
      and deterioration of consciousness to semicoma. Subsequent diffusion-weighted
      imaging revealed increased signal in the bilateral symmetric thalamus, internal
      segments of the globus pallidus, substantia nigra, and pontine tegmentum.
      Laboratory investigation indicated remarkable elevation of lactate levels in
      cerebrospinal fluid. The diagnosis was of Leigh syndrome. We think this is the
      first reported case of Leigh encephalopathy with transient abnormality of
      diffusion-weighted imaging of the white matter before apparent clinical onset.
      Leigh syndrome should be included in the differential diagnosis of abnormality of
      diffusion-weighted imaging in white matter without apparent clinical signs.

PMID- 19748056
TI  - Transverse myelitis as a rare, serious complication of Mycoplasma pneumoniae
      infection.
AB  - We report on the first published case of a Mycoplasma pneumoniae-associated
      transverse myelitis appearing in childhood and leading to persistent paraplegia
      and bowel and bladder dysfunctions. Magnetic resonance imaging of the spinal cord
      indicated extensive transverse myelitis extending from T(5)-T(12). A repeated
      scan established spinal cord atrophy in the affected area. Various therapies
      (methylprednisolone pulse therapy, plasmapheresis, and roxythromycine) produced
      no clinical effect.

PMID- 19748057
TI  - Abstracts of the 2009 World Congress on Osteoarthritis. Montreal, Quebec, Canada.
      September 10-13, 2009.

PMID- 19748058
TI  - Incretin hormones and their therapeutic potential in patients with type 2
      diabetes. Preface.

PMID- 19748059
TI  - Insulin secretion in healthy subjects and patients with Type 2 diabetes--role of
      the gastrointestinal tract.
AB  - Postprandial glycaemia is now recognised as the major determinant of average
      glycaemic control in type 2 diabetes, as assessed by glycated haemoglobin.
      Therefore, an understanding of the factors influencing both the rise in blood
      glucose and insulin secretion after a meal is fundamental to the development of
      dietary and pharmacological approaches to optimise glycaemic control. The
      gastrointestinal tract regulates the rate at which carbohydrate and other
      nutrients are absorbed and is the source of regulatory peptides that stimulate
      pancreatic insulin secretion in the setting of elevated blood glucose levels.
      This article highlights the importance of the gastrointestinal tract in insulin
      secretion and glucose homeostasis and discusses potential strategies directed at
      modification of gastrointestinal function in order to improve glycaemic control
      in the management of diabetes.

PMID- 19748060
TI  - Immunoassays for the incretin hormones GIP and GLP-1.
AB  - The measurement of the incretin hormones, glucagon-like peptide-1 (GLP-1) and
      glucose-dependent insulinotropic polypeptide (GIP), using immunologically based
      assays is made difficult by the fact that the processing of the precursor
      molecules gives rise to a number of different peptides which cross-react with
      antisera raised against the two hormones. For GLP-1, the picture is further
      complicated because of the necessity to differentiate between the intestinal and
      pancreatic proglucagon products. Finally, once secreted, both incretins are
      rapidly degraded by the enzyme dipeptidyl peptidase-4 (DPP-4) to generate
      metabolites which have lost their insulinotropic activities. These metabolites
      are the major circulating forms of the incretins, accounting for 60-80% of total
      immunoreactive GLP-1 and GIP in the peripheral plasma, while concentrations of
      the intact forms can be very low and, in some cases, barely detectable. The use
      of highly specific assays using well-characterised antisera and careful sample
      handling is therefore required for a reliable determination of incretin hormone
      concentrations.

PMID- 19748061
TI  - The contribution of incretin hormones to the pathogenesis of type 2 diabetes.
AB  - The incretin effect, that is, the postprandial augmentation of insulin secretion
      by gastrointestinal hormones, mediates approximately 50-70% of the overall
      insulin responses after a mixed meal or glucose ingestion in healthy subjects. In
      patients with type 2 diabetes, the incretin effect is markedly reduced, and this
      has been attributed to defects in the secretion and insulinotropic action of the
      two main incretin hormones, namely gastric inhibitory polypeptide (GIP) and
      glucagon-like peptide 1 (GLP-1). It has been speculated that a reduced incretin
      effect might precede the onset of hyperglycaemia in patients with type 2
      diabetes. However, the secretion and action of GIP and GLP-1 is relatively
      unaltered in normal glucose-tolerant individuals at high risk for type 2 diabetes
      (e.g., first-degree relatives) and a diminished incretin effect is also
      detectable in other types of diabetes, thereby arguing against such reasoning.
      This article will describe the defects in the incretin system in patients with
      type 2 diabetes, summarise their relevance in the development of hyperglycaemia
      and discuss the potential individual roles of GIP and GLP-1 in the pathogenesis
      of type 2 diabetes.

PMID- 19748062
TI  - Mechanisms underlying the rapid degradation and elimination of the incretin
      hormones GLP-1 and GIP.
AB  - The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent
      insulinotropic peptide (GIP, gastric inhibitory peptide) are secreted from
      intestinal L and K cells and stimulate insulin secretion from pancreatic beta
      cells. However, they are immediately inactivated mainly via N-terminal
      degradation by dipeptidyl peptidase IV (DPP IV, CD26), a specialised enzyme
      located on the cell surface enzyme of endothelial, epithelial and some other cell
      types. Cleavage by neprilysin (neutral endopeptidase) is a minor degradation
      route, and renal clearance eliminates incretin/fragments, but appears of less
      importance for regulating incretin bioactivities. Based on these observations two
      novel types of drugs for the treatment of type 2 diabetes have been developed:
      DPP IV inhibitors and DPP IV-resistant incretin analogues. Both have distinct
      advantages and disadvantages. Potential side effects of DPP IV inhibitors may
      result from affecting the bioactivity of other hormones, neuropeptides or
      chemokines and also by their cross-reactivity with DPP IV-related enzymes.

PMID- 19748063
TI  - The spectrum of antidiabetic actions of GLP-1 in patients with diabetes.
AB  - This article focusses on the antidiabetic therapeutic potential of the incretin
      hormone glucagon-like peptide-1 (GLP-1) in the treatment of patients with type 2
      diabetes mellitus (T2DM). T2DM is characterised by insulin resistance, impaired
      glucose-induced insulin secretion and inappropriately regulated glucagon
      secretion, which in combination eventually result in hyperglycaemia and, in the
      longer term, microvascular and macrovascular diabetic complications. Traditional
      treatment modalities - even multidrug approaches - for T2DM are often
      unsatisfactory in making patients reach glycaemic goals as the disease progresses
      caused by a steady, relentless decline in pancreatic beta-cell function.
      Furthermore, current treatment modalities are often limited by inconvenient
      dosing regimens and safety and tolerability issues, the latter including
      hypoglycaemia, body weight gain, oedema and gastrointestinal side effects.
      Therefore, the actions of GLP-1, which include the potentation of meal-induced
      insulin secretion and trophic effects on the beta-cell, have attracted a lot of
      interest. GLP-1 also inhibits glucagon secretion and suppresses food intake and
      appetite.

PMID- 19748064
TI  - Exenatide and liraglutide: different approaches to develop GLP-1 receptor
      agonists (incretin mimetics)--preclinical and clinical results.
AB  - The GLP-1 analogues exenatide and liraglutide stimulate insulin secretion and
      inhibit glucagon output in a glucose-dependent manner, slow gastric emptying and
      decrease appetite. The injectable glucagon-like peptide-1 (GLP-1) receptor
      agonist exenatide significantly improves glycaemic control, with average
      reductions in HbA1c of about 1.0% point, fasting plasma glucose of about 1.4 mmol
      l(-1), and causes a weight loss of approximately 2-3 kg after 30 weeks of
      treatment. The adverse effects are transient nausea and vomiting. The long-acting
      once-daily human GLP-1 receptor agonist liraglutide reduces HbA1c by about 1.0
      2.0% point, weight by 1-3 kg and seems to have fewer gastrointestinal side
      effects than exenatide. The final place of the GLP-1 receptor agonists in the
      diabetes treatment algorithm will be clarified when we have long-term trials with
      cardiovascular end-points and data illustrating the effects on the progression of
      type 2 diabetes.

PMID- 19748065
TI  - Mechanism of action of inhibitors of dipeptidyl-peptidase-4 (DPP-4).
AB  - Dipeptidyl-peptidase IV (DPP-4) inhibitors inhibit the degradation of the
      incretins, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic
      peptide (GIP). The first available DPP-4 inhibitors are sitagliptin and
      vildagliptin. These compounds are orally active and have been shown to be
      efficacious and well tolerated. Two additional DPP-4 inhibitors are under review,
      and there are several others in clinical development. This article gives an
      overview on the mechanism of action of DPP-4 inhibitors and focuses on their
      development and their important physiological actions with regard to the
      treatment of type 2 diabetes.

PMID- 19748066
TI  - Clinical results of treating type 2 diabetic patients with sitagliptin,
      vildagliptin or saxagliptin--diabetes control and potential adverse events.
AB  - Inhibition of dipeptidyl peptidase-4 (DPP-4) is a novel oral treatment for type 2
      diabetes. DPP-4 inhibition increases insulin secretion and reduces glucagon
      secretion by preventing the inactivation of glucagon-like peptide-1 (GLP-1),
      thereby lowering glucose levels. Several DPP-4 inhibitors are in clinical
      development; more studies exist for sitagliptin and vildagliptin. They improve
      metabolic control in type 2 diabetes in monotherapy and also in combination with
      metformin, sulphonylurea and thiazolidinediones. HbA(1c) is reduced by
      approximately 0.6-1.1% in studies up to 52 weeks. Similar, although more limited,
      results were obtained for saxagliptin. DPP-4 inhibitors are safe and tolerable
      with no increased risk of adverse events compared to placebo and have a low risk
      of hypoglycaemia. DPP-4 inhibitors are body weight-neutral. The DPP-4 inhibitors
      are recommended for use in the early stage of type 2 diabetes, in combination
      with metformin in subjects with inadequate glycaemic control. DPP-4 inhibition
      may also be used in combination with sulphonylurea and thiazolidinediones and
      potentially also in combination with insulin. The durability and long-term safety
      of DPP-4 inhibitors remain to be established.

PMID- 19748067
TI  - Therapeutic potential for GIP receptor agonists and antagonists.
AB  - Glucose-dependent insulinotropic polypeptide (GIP or gastric inhibitory
      polypeptide) is a 42-amino-acid hormone, secreted from the enteroendocrine K
      cells, which has insulin-releasing and extrapancreatic glucoregulatory actions.
      However, the unfavourable pharmacokinetic profile and the weak biological effects
      of native GIP limit its effectiveness for the treatment of type 2 diabetes. To
      overcome this, longer-acting GIP agonists exhibiting enzymatic stability and
      enhanced bioactivity have been generated and successfully tested in animal models
      of diabetes. Thus, GIP receptor agonists offer one of the newest classes of
      potential antidiabetic drug. GIP is also known to play a role in lipid metabolism
      and fat deposition. Accordingly, both genetic and chemical ablation of GIP
      signalling in mice with obesity-diabetes can protect against, or even reverse
      many of the obesity-associated metabolic disturbances. Strong parallels exist
      with the beneficial metabolic effects of Roux-en-Y gastric bypass in obese,
      insulin-resistant humans that surgically ablates GIP-secreting K cells. The
      purpose of this article is to highlight the therapeutic potential of GIP-based
      therapeutics in the treatment of type 2 diabetes and obesity.

PMID- 19748068
TI  - Incretin-based therapy: how do incretin mimetics and DPP-4 inhibitors fit into
      treatment algorithms for type 2 diabetic patients?
AB  - Incretin-based antidiabetic medications have been approved for clinical use for
      approximately two to three years. While their major clinical characteristics have
      been known from clinical trials, the discussion now focuses on the best clinical
      use of GLP-1 receptor agonists (incretin mimetics) and inhibitors of the protease
      dipeptidyl peptidase-4 (DPP-4). Any novel drug will not fully disclose its
      spectrum of beneficial and adverse activity before long-term trials with clinical
      endpoints are available. This, typically, will last 5-8 years. Nevertheless,
      there are convincing reasons to use incretin mimetics and DPP-4 inhibitors even
      in the absence of such results. This decision should be based on specific patient
      characteristics and (expected) treatment results, in comparison to other
      available treatment options. The present manuscript tries to describe the current
      state-of-the-art of using incretin mimetics and DPP-4 inhibitors in clinical
      practice, including an attempt to suggest their place in treatment algorithms for
      type 2-diabetic patients.

PMID- 19748069
TI  - Perinatal stroke.

PMID- 19748070
TI  - Finding the features that represent stimuli.
AB  - We develop a model for finding the features that represent a set of stimuli, and
      apply it to the Leuven Concept Database. The model combines the feature
      generation and similarity judgment task data, inferring whether each of the
      generated features is important for explaining the patterns of similarity between
      stimuli. Across four datasets, we show that features range from being very
      important to very unimportant, and that a small subset of important features is
      adequate to describe the similarities. We also show that the features inferred to
      be more important are intuitively reasonable, and present analyses showing that
      important features tend to focus on narrow sets of stimuli, providing information
      about the category structures that organize the stimuli into groups.

PMID- 19748071
TI  - Surgical treatment of nonparasitic cysts of the liver: open versus laparoscopic
      treatment.
AB  - BACKGROUND: The aim of this study was to compare the immediately postoperative
      and follow-up results of open and laparoscopic surgery of hepatic cysts in a
      tertiary hepatobiliary referral center. MATERIALS AND METHODS: From March 1999 to
      February 2007, 59 patients underwent surgical treatment for nonparasitic liver
      cysts. Patients were assigned to the laparoscopic (n = 42) or open group (n = 17)
      for analysis. RESULTS: Three conversions to open procedures had to be performed
      in the laparoscopic group. One patient had to be reoperated because of a bile
      leakage in the laparoscopic group. Follow-up examination showed 2 recurrences in
      the laparoscopic and 3 in the open group. Three out of 17 patients in the open
      group had to be operated for incisional hernias. Time to previous activities was
      significantly shorter after laparoscopy. CONCLUSIONS: Laparoscopic treatment of
      symptomatic nonparasitic liver cysts is superior concerning short- and long-term
      results in a vast majority of cases.

PMID- 19748072
TI  - Analyses of mental contamination: Part II, individual differences.
AB  - Recent research on mental contamination (internal, psychological feelings of
      dirtiness) has focused primarily on examining the experimental variables
      necessary to provoke contamination-related thoughts, feelings and behaviour; yet,
      relatively little is known regarding the individual differences among
      participants' mental contamination responses to these situational and
      experimental characteristics. The purpose of this study was to determine whether
      variables associated with symptoms, beliefs and appraisals could predict the
      experience of mental contamination after an established provocation. Female
      undergraduate students (n = 70 from Part I of this study; Elliott & Radomsky,
      2009), completed a series of questionnaires then listened to an audio recording
      and imagined that they were receiving a forced, non-consensual kiss from a man
      described as moral or immoral. Participants indicated the presence and degree of
      mental contamination and appraisals of the man and act, then completed a
      behavioural task for which spontaneous washing was recorded. Results indicated
      that, although symptoms of physical contamination were able to predict feelings
      of mental contamination, appraisal variables emerged as unique predictors of
      feelings of mental contamination. Results are discussed in terms of cognitive
      behavioural conceptualizations of and treatments for contamination fears.

PMID- 19748073
TI  - Phthalates exposure and attention-deficit/hyperactivity disorder in school-age
      children.
AB  - BACKGROUND: Very few studies have examined the association between attention
      deficit/hyperactivity disorder (ADHD) and phthalate exposure in humans. The aim
      of this study was to investigate the impact of phthalates on symptoms of ADHD in
      school-age children. METHODS: A cross-sectional examination of urine phthalate
      concentrations was performed, and scores on measures of ADHD symptoms and
      neuropsychological dysfunction with regard to attention and impulsivity were
      obtained from 261 Korean children, age 8-11 years. RESULTS: Mono-2-ethylheyl
      phthalate (MEHP) and mono-2-ethyl-5-oxohexylphthalate (MEOP) for metabolites of
      Di-2-ethylhexylphthalate (DEHP) and mono-n-butyl phthalate (MNBP) for metabolites
      of dibutyl phthalate (DBP) were measured in urine samples. The mean
      concentrations of MEHP, MEOP, and MNBP were 34.0 microg/dL (SD = 36.3; range: 2.1
      386.7), 23.4 microg/dL (SD = 23.0; range: .75-244.8), and 46.7 microg/L (SD =
      21.4; range: 13.2-159.3), respectively. After adjustment for covariates, teacher
      rated ADHD scores were significantly associated with DEHP metabolites but not
      with DBP metabolites. We also found significant relationships between the urine
      concentrations of metabolites for DBP and the number of omission and commission
      errors in continuous performance tests (CPT) after adjustment for covariates.
      CONCLUSION: The present study showed a strong positive association between
      phthalate metabolites in urine and symptoms of ADHD among school-age children.

PMID- 19748074
TI  - The role of DNA copy number variation in schizophrenia.
AB  - Schizophrenia is a major psychiatric disease with strong evidence of genetic risk
      factors. Recent studies based on genome-wide study of copy number variations
      (CNVs) have detected novel recurrent submicroscopic copy number changes,
      including recurrent deletions at 1q21.11, 15q11.3, 15q13.3, and the recurrent CNV
      at the 2p16.3 neurexin 1 locus. These schizophrenia susceptibility CNV loci
      demonstrate that schizophrenia is, at least in part, genetic in origin and
      provide the basis for further investigation of mutations associated with the
      disease. The studies combined have also established the role of rare and-in
      sporadic cases-de novo variants in schizophrenia. Furthermore, neuronal-related
      genes and genetic pathways are starting to emerge from the CNV loci associated
      with schizophrenia. Here, we review the major findings in the recent literature,
      which begin to unravel the genetic and biological architecture of this complex
      human neuropsychiatric disorder.

PMID- 19748075
TI  - Automatic mood-congruent amygdala responses to masked facial expressions in major
      depression.
AB  - BACKGROUND: Cognitive theories of depression predict mood-congruent negative
      biases already at automatic stages of processing, although several behavioral
      studies seem to contradict this notion. That is, depression should potentiate
      emotional reactivity to negative emotional cues, whereas it should reduce
      reactivity in response to positive emotional stimuli. Assessing neurobiological
      substrates of automatic emotion processing might be a more sensitive challenge
      for automatic negative bias in depression than behavioral measures. METHODS: In
      30 acutely depressed inpatients and 26 healthy control subjects, automatic
      amygdala responses to happy and sad facial expressions were assessed by means of
      functional magnetic resonance imaging (fMRI) at 3 Tesla. To examine automatic
      responses, a presentation paradigm using subliminal, backward-masked stimuli was
      employed. A detection task was administered to assess participants' awareness of
      the masked emotional faces presented in the fMRI experiment. RESULTS: Detection
      performance was at chance level for both patients and healthy control subjects,
      suggesting that the neurobiological reactions took place in absence of conscious
      awareness of the emotional stimuli. A robust emotion by group interaction was
      observed in the right amygdala. Whereas healthy control subjects demonstrated
      stronger responses to happy faces, depressed patients showed the opposite.
      Furthermore, amygdala responsiveness to happy facial expression was negatively
      correlated with current depression severity. CONCLUSIONS: Depressed patients
      exhibit potentiated amygdala reactivity to masked negative stimuli along with a
      reduced responsiveness to masked positive stimuli compared with healthy
      individuals. Thus, depression is characterized by mood-congruent processing of
      emotional stimuli in the amygdala already at an automatic level of processing.

PMID- 19748076
TI  - Neurobiological basis of failure to recall extinction memory in posttraumatic
      stress disorder.
AB  - BACKGROUND: A clinical characteristic of posttraumatic stress disorder (PTSD) is
      persistently elevated fear responses to stimuli associated with the traumatic
      event. The objective herein is to determine whether extinction of fear responses
      is impaired in PTSD and whether such impairment is related to dysfunctional
      activation of brain regions known to be involved in fear extinction, viz.,
      amygdala, hippocampus, ventromedial prefrontal cortex (vmPFC), and dorsal
      anterior cingulate cortex (dACC). METHODS: Sixteen individuals diagnosed with
      PTSD and 15 trauma-exposed non-PTSD control subjects underwent a 2-day fear
      conditioning and extinction protocol in a 3-T functional magnetic resonance
      imaging scanner. Conditioning and extinction training were conducted on day 1.
      Extinction recall (or extinction memory) test was conducted on day 2
      (extinguished conditioned stimuli presented in the absence of shock). Skin
      conductance response (SCR) was scored throughout the experiment as an index of
      the conditioned response. RESULTS: The SCR data revealed no significant
      differences between groups during acquisition and extinction of conditioned fear
      on day 1. On day 2, however, PTSD subjects showed impaired recall of extinction
      memory. Analysis of functional magnetic resonance imaging data showed greater
      amygdala activation in the PTSD group during day 1 extinction learning. During
      extinction recall, lesser activation in hippocampus and vmPFC and greater
      activation in dACC were observed in the PTSD group. The magnitude of extinction
      memory across all subjects was correlated with activation of hippocampus and
      vmPFC during extinction recall testing. CONCLUSIONS: These findings support the
      hypothesis that fear extinction is impaired in PTSD. They further suggest that
      dysfunctional activation in brain structures that mediate fear extinction
      learning, and especially its recall, underlie this impairment.

PMID- 19748077
TI  - Deficits in syntaxin 1 phosphorylation in schizophrenia prefrontal cortex.
AB  - BACKGROUND: Schizophrenia has been described as a disease of the synapse. On the
      basis of previous studies reporting reductions in the levels and activity of CK2
      (also know as casein kinase 2 or II) in the brain of subjects with schizophrenia,
      we hypothesized that CK2-mediated phosphorylation of the presynaptic protein
      syntaxin 1 (Stx 1) is deficient in schizophrenia. This in turn could affect the
      binding of Stx 1 to its protein partners and result in abnormal neurotransmitter
      release and synaptic transmission. METHODS: We analyzed post mortem prefrontal
      cortex samples from 15 schizophrenia cases and matched controls by quantitative
      immunoblotting. RESULTS: In addition to replicating previous findings of reduced
      CK2 levels, we show that as predicted, the deficit in CK2 correlates with a
      deficit in phospho-Stx 1. In contrast, we find that these deficits are not
      present in depression cases. Further, we show that the reduced levels of CK2 and
      phospho-Stx 1 are not due to treatment with antipsychotic drugs (APDs). In fact,
      APDs seem to increase both CK2 and phospho-Stx 1, suggesting that their
      therapeutic action may be associated with the reversal of these deficits.
      Finally, we show that lower phospho-Stx 1 levels are associated with reduced
      binding of Stx 1 to SNAP-25 and MUNC18 and decreased SNARE complex formation.
      CONCLUSIONS: Our findings constitute the first report of altered phosphorylation
      of a key component for neurotransmitter release in humans and suggest that
      regulation of Stx 1 by CK2-mediated phosphorylation could play a role in the
      pathophysiology of schizophrenia.

PMID- 19748078
TI  - Laboratory induced aggression: a positron emission tomography study of aggressive
      individuals with borderline personality disorder.
AB  - BACKGROUND: Borderline personality disorder (BPD) is often associated with
      symptoms of impulsive aggression, which poses a threat to patients themselves and
      to others. Preclinical studies show that orbital frontal cortex (OFC) plays a
      role in regulating impulsive aggression. Prior work has found OFC dysfunction in
      BPD. METHODS: We employed a task to provoke aggressive behavior, the Point
      Subtraction Aggression Paradigm (PSAP), which has never previously been used
      during functional brain imaging. Thirty-eight BPD patients with intermittent
      explosive disorder (BPD-IED) and 36 age-matched healthy control subjects (HCs)
      received (18)fluoro-deoxyglucose positron emission tomography ((18)FDG-PET) on
      two occasions with a provocation and nonprovocation version of the PSAP. Mean
      relative glucose metabolism was measured throughout the cortex, and difference
      scores (provoked - nonprovoked) were calculated. A whole brain exploratory
      analysis for the double difference of BPD-IED - HC for provoked - nonprovoked was
      also conducted. RESULTS: BPD-IED patients were significantly more aggressive than
      HCs on the PSAP. BPD-IED patients also increased relative glucose metabolic rate
      (rGMR) in OFC and amygdala when provoked, while HCs decreased rGMR in these
      areas. However, HCs increased rGMR in anterior, medial, and dorsolateral
      prefrontal regions during provocation more than BPD-IED patients. CONCLUSIONS:
      Patients responded aggressively and showed heightened rGMR in emotional brain
      areas, including amygdala and OFC, in response to provocation but not in more
      dorsal brain regions associated with cognitive control of aggression. In
      contrast, HCs increased rGMR in dorsal regions of PFC during aggression
      provocation, brain regions involved in top-down cognitive control of aggression,
      and, more broadly, of emotion.

PMID- 19748079
TI  - gamma-Aminobutyric acid cells with cocaine-induced DeltaFosB in the ventral
      tegmental area innervate mesolimbic neurons.
AB  - BACKGROUND: The transcription factor DeltaFosB is implicated in the plasticity
      induced by drugs of abuse. We showed that psychostimulants induce DeltaFosB in
      gamma-aminobutyric acid (GABA) cells of a caudal subregion of the ventral
      tegmental area (VTA) that was named tail of the VTA (tVTA). Although tVTA mostly
      shares VTA inputs, its outputs remain to be characterized. METHODS: The tVTA
      efferents were studied by iontophoretic injections of the anterograde tracer
      biotinylated dextran amine (BDA). To further study VTA inputs arising from tVTA,
      injections of the retrograde tracer Fluoro-Gold were combined with multiple
      labeling by immunohistochemistry in rats treated with cocaine. Indirect
      projections from the tVTA to the nucleus accumbens were assessed with a double
      tracing approach, cholera toxin B subunit (CTB) being delivered in the nucleus
      accumbens and BDA in the tVTA. RESULTS: Tract-tracing studies showed that tVTA
      heavily projects to the midbrain dopaminergic system and revealed terminal
      appositions with dopamine cells in the VTA. Double-labeling studies demonstrated
      that this tVTA output is mostly GABAergic, includes cells in which cocaine
      exposure induces DeltaFosB, and displays appositions to dopamine cells projecting
      to the nucleus accumbens. CONCLUSIONS: The GABA neurons expressing DeltaFosB in
      the tVTA after cocaine exposure project to the dopamine mesolimbic neurons.

PMID- 19748080
TI  - A meta-analysis of the corpus callosum in autism.
AB  - BACKGROUND: Previous magnetic resonance imaging (MRI) studies have reported
      reductions in corpus callosum (CC) total area and CC regions in individuals with
      autism. However, studies have differed concerning the magnitude and/or region
      contributing to CC reductions. The present study determined the significance and
      magnitude of reductions in CC total and regional area measures in autism. METHOD:
      PubMed and PsycINFO databases were searched to identify MRI studies examining
      corpus callosum area in autism. Ten studies contributed data from 253 patients
      with autism (mean age = 14.58, SD = 6.00) and 250 healthy control subjects (mean
      age = 14.47, SD = 5.31). Of these 10 studies, 8 reported area measurements for
      corpus callosum regions (anterior, mid/body, and posterior), and 6 reported area
      for Witelson subdivisions. Meta-analytic procedures were used to quantify
      differences in total and region CC area measurements. RESULTS: Total CC area was
      reduced in autism and the magnitude of the reduction was medium (weighted mean d
      = .48, 95% confidence interval [CI] = .30-.66). All regions showed reductions in
      size with the magnitude of the effect decreasing caudally (anterior d = .49,
      mid/body d = .43, posterior d = .37). Witelson subdivision 3 (rostral body)
      showed the largest effect, indicating greatest reduction in the region containing
      premotor/supplementary motor neurons. CONCLUSIONS: Corpus callosum reductions are
      present in autism and support the aberrant connectivity hypothesis. Future
      diffusion tensor imaging studies examining specific fiber tracts connecting the
      hemispheres are needed to identify the cortical regions most affected by CC
      reductions.

PMID- 19748081
TI  - The five-factor model of personality and borderline personality disorder: a
      genetic analysis of comorbidity.
AB  - BACKGROUND: Recently, the nature of personality disorders and their relationship
      with normal personality traits has received extensive attention. The five-factor
      model (FFM) of personality, consisting of the personality traits neuroticism,
      extraversion, openness to experience, agreeableness, and conscientiousness, is
      one of the proposed models to conceptualize personality disorders as maladaptive
      variants of continuously distributed personality traits. METHODS: The present
      study examined the phenotypic and genetic association between borderline
      personality and FFM personality traits. Data were available for 4403 monozygotic
      twins, 4425 dizygotic twins, and 1661 siblings from 6140 Dutch, Belgian, and
      Australian families. RESULTS: Broad-sense heritability estimates for neuroticism,
      agreeableness, conscientiousness, extraversion, openness to experience, and
      borderline personality were 43%, 36%, 43%, 47%, 54%, and 45%, respectively.
      Phenotypic correlations between borderline personality and the FFM personality
      traits ranged from .06 for openness to experience to .68 for neuroticism.
      Multiple regression analyses showed that a combination of high neuroticism and
      low agreeableness best predicted borderline personality. Multivariate genetic
      analyses showed the genetic factors that influence individual differences in
      neuroticism, agreeableness, conscientiousness, and extraversion account for all
      genetic liability to borderline personality. Unique environmental effects on
      borderline personality, however, were not completely shared with those for the
      FFM traits (33% is unique to borderline personality). CONCLUSIONS: Borderline
      personality shares all genetic variation with neuroticism, agreeableness,
      conscientiousness, and extraversion. The unique environmental influences specific
      to borderline personality may cause individuals with a specific pattern of
      personality traits to cross a threshold and develop borderline personality.

PMID- 19748082
TI  - Suppression of alcohol preference by naltrexone in the rhesus macaque: a critical
      role of genetic variation at the micro-opioid receptor gene locus.
AB  - BACKGROUND: The role of a nonsynonymous A118G polymorphism of the human micro
      opioid receptor gene (OPRM1) for alcohol reward and therapeutic efficacy of
      naltrexone remains controversial. A functionally equivalent OPRM1 C77G
      polymorphism in rhesus macaques allows this to be addressed under controlled
      experimental conditions. METHODS: Twenty-one rhesus macaques (13 female rhesus
      macaques, 8 male rhesus macaques) were genotyped for OPRM1 C77G and studied
      during 1-hour sessions for preference between an aspartame-sweetened alcohol
      solution (8.4% vol/vol) and a nonalcoholic control fluid in a baseline session
      followed by naltrexone (1 mg/kg) and vehicle treatment in a counterbalanced
      within-subject design. RESULTS: Mixed-model analysis of variance controlling for
      baseline and sex showed a highly significant (p = .003) interaction between
      genotype and treatment. Post hoc analysis showed that vehicle-treated 77G
      carriers had markedly higher alcohol preference than 77C homozygous subjects (p =
      .001). Following naltrexone administration, 77G carriers decreased their
      preference (p = .002) and no longer differed from 77C homozygous subjects. In
      contrast, the latter group was unaffected by treatment and, in fact, showed a
      trend-level increase of preference following naltrexone. CONCLUSIONS: These
      results support a critical pharmacogenetic role of OPRM1 variation for
      therapeutic efficacy of naltrexone.

PMID- 19748084
TI  - Simultaneous determination in situ of DNA fragmentation and 8-oxoguanine in human
      sperm.
AB  - Deoxyribonucleic acid fragmentation and oxidative DNA damage were simultaneously
      determined in the same sperm cell, incubating with an 8-oxoguanine DNA probe on
      human spermatozoa processed by the sperm chromatin dispersion test. The assay was
      validated by incubation with agents that induce DNA fragmentation with or without
      oxidative base damage. In all samples examined, increased levels of 8-oxoguanine
      were present only in those spermatozoa with fragmented DNA, suggesting a link
      between both DNA damage types.

PMID- 19748085
TI  - Embryonic heart rates.

PMID- 19748086
TI  - Discontinuation of hormone therapy in the French GAZEL cohort 1990-2006.
AB  - OBJECTIVE: To analyze changes in hormone therapy (HT) use after the publication
      of the Women's Health Initiative (WHI) results, in a country (France) where HT is
      different from that assessed in the WHI. DESIGN: Longitudinal study. SETTING:
      Women in the GAZEL cohort of employees of the French national power company.
      PARTICIPANT(S): One thousand six hundred five postmenopausal women ever-users of
      HT. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Discontinuation of HT.
      RESULT(S): Rates of discontinuation were higher after 2002: 65% of users who
      began HT in 1998 were still using it after 5 years. In contrast, >90% of those
      who began before 1994 were still using it after 5 years. Discontinuation was
      associated with women's social and medical characteristics and with factors
      related to side effects and expectations concerning HT. After adjustment for
      these factors, women were twice as likely to stop HT after publication of the
      WHI. CONCLUSION(S): Even in France, publication of the WHI has led to a decline
      in HT use.

PMID- 19748088
TI  - Cytogenetic analysis of early nonviable pregnancies after assisted reproduction
      treatment.
AB  - In our series, a very high prevalence of chromosomal abnormalities was observed
      in spontaneous miscarriages, irrespective of how pregnancy was achieved, by
      assisted reproductive technology (ART) or natural conception. This high
      prevalence was equally represented in both groups, with no statistical difference
      in type of chromosomal abnormalities or in total frequency; however, the
      incidence of monosomy X is increased and the polyploidies are decreased in
      abortus after intracytoplasmic sperm injection (ICSI) when it is compared with
      miscarriages after spontaneous gestations.

PMID- 19748089
TI  - Embryo transfer practices in the United States: a survey of clinics registered
      with the Society for Assisted Reproductive Technology.
AB  - OBJECTIVE: To gain a better understanding of factors influencing clinicians'
      embryo transfer practices. DESIGN: Cross-sectional survey. SETTING: Web-based
      survey conducted in December 2008 of individuals practicing IVF in centers
      registered with the Society for Assisted Reproductive Technology (SART).
      PATIENT(S): None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Prevalence of
      clinicians reporting following embryo transfer guidelines recommended by the
      American Society for Reproductive Medicine (ASRM), prevalence among these
      clinicians to deviate from ASRM guidelines in commonly encountered clinical
      scenarios, and practice patterns related to single embryo transfer. RESULT(S):
      Six percent of respondents reported following their own, independent guidelines
      for the number of embryos to transfer after IVF. Of the 94% of respondents who
      reported routinely following ASRM embryo transfer guidelines, 52% would deviate
      from these guidelines for patient request, 51% for cycles involving the transfer
      of frozen embryos, and 70% for patients with previously failed IVF cycles. All
      respondents reported routinely discussing the risks of multiple gestations
      associated with standard embryo transfer practices, whereas only 34% reported
      routinely discussing single embryo transfer with all patients. CONCLUSION(S):
      Although the majority of clinicians responding to our survey reported following
      ASRM embryo transfer guidelines, at least half would deviate from these
      guidelines in a number of different situations.

PMID- 19748090
TI  - Observations of external ear--an Indian study.
AB  - Somatoscopy of the external ear provides a general idea of the shape of an ear,
      form of the helix, presence (or absence) of Darwin's tubercle and of the
      attachment of an ear lobe to a cheek, etc. It is of great importance not only to
      physical anthropologists but also to plastic surgeons, physicians and forensic
      scientists. There is no detailed somatoscopic study of the ear morphology
      concerning the entire Indian subcontinent. Hence, in the present study an attempt
      has been made to report the frequency of various somatoscopic features of various
      parts of the auricle of adult males and females who live in the central region of
      India. In both sexes oval-shaped ears and normally rolled helix were most common.
      The preauricular region was found to be clear with very few cases of the
      occurrence of pits and sinuses. Free lobules were more frequent among females
      than males but it was vice versa for Darwin's tubercle. The position of the ear's
      upper edge was most commonly located at the eyebrow tail while its lower edge was
      located at an upper lip level in both sexes. Hypoplastic lobules were noted in
      one-fifth of males but were very rare among females. Very few cases of lop ear,
      preauricular appendage and preauricular pit were observed. Some of these
      somatoscopic features act as soft biometric traits that improve the performance
      of the primary biometric system of personal identification. Somatoscopy of
      external ear acts as an aid to surgeons while reconstructing deformed ears and
      also helps physicians in detecting anomalies, for example, Edward's, cleft
      lip/cleft palate syndromes.

PMID- 19748091
TI  - Are changes in body dimensions of adult females from Italy (Sardinia and Latium)
      related to secular trend?
AB  - This paper presents secular changes in height, weight, sitting height, relative
      sitting height, BMI and estimated lower limb length in two samples of Italian
      adult females from Sardinia (Cagliari) and Latium (Rieti). The samples consist of
      579 healthy women from the province of Cagliari and 138 from the town of Rieti,
      aged 20.0-39.9 years, measured in the period 2003-2006. The women were divided
      into four 5-year age groups. The anthropometric variables were considered
      according to different socioeconomic status (SES) in the Cagliari sample, while
      the Rieti sample was considered as a whole, as the SES was homogeneous. ANOVA
      results suggest that the secular trend was very slow or had come to a halt in the
      Rieti sample but continues in the Cagliari sample, as shown by the statistically
      significant differences for estimated lower limb length (p<or=0.02), and relative
      sitting height (p<or=0.05). However, these differences disappear after ANCOVA
      with sibship size and socioeconomic status controlled for, suggesting that they
      depend mainly on the composition of the Cagliari sample in terms of SES.
      Therefore, it can be hypothesised that the secular trend might be very slow or
      has stopped in the Cagliari subsamples homogeneous for SES.

PMID- 19748092
TI  - Diffuse cavernous hemangioma of the left leg, vulva, uterus, and placenta of a
      pregnant woman.

PMID- 19748093
TI  - Prospective study of matrix metalloproteinase-9 and risk of myocardial infarction
      and stroke in older men and women.
AB  - OBJECTIVES: The endopeptidase matrix metalloproteinase-9 (MMP-9) is implicated in
      atherosclerotic plaque rupture. We investigate prospective associations between
      MMP-9 and MI or stroke in an older general population cohort, accounting for
      established and novel cardiovascular risk factors. METHODS: Baseline serum MMP-9
      was measured in incident MI (n=368) and stroke (n=299) cases and two controls per
      case, 'nested' in prospective studies of 4252 men and 4286 women aged 60-79
      years, sampled from General Practices in Britain in 1998-2000, with 7-year follow
      up for fatal and non-fatal MI and stroke. RESULTS: Geometric mean MMP-9 was 528
      ng/mL (IQR 397, 743) in MI cases compared to 501 ng/mL (IQR 370, 743) in
      controls, p=0.10. Participants in the top compared to bottom third of MMP-9
      levels had an age-adjusted odds ratio for MI of 1.53 (95% CI 1.09, 2.13), which
      attenuated to 1.18 (95% CI 0.81, 1.70) after adjustment for established and novel
      cardiovascular risk factors. There was weak evidence that OR differed according
      to pre-existing CVD; the OR for MI in 187 participants with pre-existing CVD was
      2.20 (1.04, 4.64) and 1.24 (0.84, 1.82) in 715 participants without (LR test for
      interaction p=0.06). Geometric mean MMP-9 levels were higher in stroke cases than
      controls; 522ng/mL (IQR 363, 673) vs 487 (IQR 393, 704), p=0.045; however
      adjustments similarly attenuated the associations. CONCLUSIONS: While serum MMP-9
      is univariately associated with risk of MI and stroke, it is not a strong
      independent risk marker for either.

PMID- 19748094
TI  - Paraoxonase 2 (PON2) decreases high glucose-induced macrophage triglycerides (TG)
      accumulation, via inhibition of NADPH-oxidase and DGAT1 activity: studies in PON2
      deficient mice.
AB  - OBJECTIVE: The present study investigates the role of paraoxonase 2 (PON2) in the
      attenuation of macrophage triglycerides (TG) biosynthesis, and oxidative stress,
      under diabetic conditions. METHODS: Peritoneal macrophages (MPM) from PON2
      deficient and from C57BL/6 control mice were harvested and cultured under normal
      (5mM) or high glucose concentration (30mM), and evaluated for cellular TG
      metabolism as well as for their oxidative stress. RESULTS: In PON2-deficient MPM
      vs. control MPM, under diabetic conditions (high glucose concentration), we
      observed substantial increment in TG accumulation (3 fold), TG biosynthesis (2.6
      fold) and microsomal diacylglycerol acyltransferase1 (DGAT1) activity (+60%).
      Furthermore, in these cells we have demonstrated increased oxidative stress, as
      expressed by significant increment in cellular oxidative stress (+25%),
      macrophage-mediated LDL oxidation (+41%) and expression of the receptor for
      advanced glycation end products - RAGE (+18%). Apocynin, an NADPH-oxidase
      inhibitor, abolished the increment in MPM TG accumulation, MPM TG biosynthesis,
      and microsomal DGAT1 activity, as a result of PON2-deficiency, under diabetic
      conditions. CONCLUSION: We conclude that PON2 has a significant protective role
      against macrophage triglyceride accumulation, macrophage TG biosynthesis,
      microsomal DGAT1 activity and macrophage oxidative stress, under high glucose
      concentrations. We suggest that this protective effect may be mediated by PON2
      through the attenuation of NADPH-oxidase activity. The use of appropriate means
      to increase macrophage PON2 expression can lead to attenuation in macrophage TG
      accumulation and in cellular oxidative stress, under diabetic conditions, and
      thus may contribute to the decrement in macrophage atherogenicity and foam cell
      formation, attenuating the development of vascular complications in diabetes
      mellitus.

PMID- 19748095
TI  - Associations between COX-2 polymorphisms, blood cholesterol and risk of acute
      coronary syndrome.
AB  - BACKGROUND: The use of specific COX-2 inhibitors in cancer prevention has been
      associated with higher risk of acute coronary syndrome (ACS) and myocardial
      infarction. The aim of this study was to investigate if the polymorphisms COX2
      T8473C (rs5275), and COX2 A-1195G (rs689466), which modify the enzyme levels of
      COX-2, were associated with risk of ACS and if alcohol intake, smoking, and use
      of NSAID would modify the associations. We also wanted to investigate
      associations with blood lipid levels. METHODS: A case-cohort study including 1031
      ACS cases and a sub-cohort of 1703 persons was nested within the population-based
      prospective study Diet, Cancer and Health of 57,053 individuals aged 55-64 at
      recruitment 1993-1997. RESULTS: Male variant allele carriers of COX-2 T8473C were
      at lower risk of ACS (IRR=0.75, CI=0.61-0.93, p=0.008) than homozygous wildtype
      carriers. There were no statistically significant interactions between genotypes
      and alcohol intake, smoking and NSAID use in relation to risk of ACS. Among
      males, there was interaction between COX-2 T8473C and alcohol in relation to
      total cholesterol, non-HDL cholesterol and LDL levels (p for interaction: 0.003,
      0.007 and 0.01, respectively), such that variant allele carriers with low alcohol
      intake had the lowest lipid levels. No statistically significant associations
      were observed in females. CONCLUSION: This study suggests that genetically
      determined COX-2 levels are associated with risk of ACS and blood lipid levels
      among males. No consistent associations were found for females.

PMID- 19748096
TI  - Cox-2 polymorphisms and cardiovascular disease: elucidating the hidden side of
      the disease.

PMID- 19748097
TI  - Fast chromatographic method for the determination of dyes in beverages by using
      high performance liquid chromatography--diode array detection data and second
      order algorithms.
AB  - A fast chromatographic methodology is presented for the analysis of three
      synthetic dyes in non-alcoholic beverages: amaranth (E123), sunset yellow FCF
      (E110) and tartrazine (E102). Seven soft drinks (purchased from a local
      supermarket) were homogenized, filtered and injected into the chromatographic
      system. Second order data were obtained by a rapid LC separation and DAD
      detection. A comparative study of the performance of two second order algorithms
      (MCR-ALS and U-PLS/RBL) applied to model the data, is presented. Interestingly,
      the data present time shift between different chromatograms and cannot be
      conveniently corrected to determine the above-mentioned dyes in beverage samples.
      This fact originates the lack of trilinearity that cannot be conveniently pre
      processed and can hardly be modelled by using U-PLS/RBL algorithm. On the
      contrary, MCR-ALS has shown to be an excellent tool for modelling this kind of
      data allowing to reach acceptable figures of merit. Recovery values ranged
      between 97% and 105% when analyzing artificial and real samples were indicative
      of the good performance of the method. In contrast with the complete separation,
      which consumes 10 mL of methanol and 3 mL of 0.08 mol L(-1) ammonium acetate, the
      proposed fast chromatography method requires only 0.46 mL of methanol and 1.54 mL
      of 0.08 mol L(-1) ammonium acetate. Consequently, analysis time could be reduced
      up to 14.2% of the necessary time to perform the complete separation allowing
      saving both solvents and time, which are related to a reduction of both the costs
      per analysis and environmental impact.

PMID- 19748098
TI  - Reversed-phase high-performance liquid chromatography-electrospray mass
      spectrometry profiling of transgenic and non-transgenic maize for cultivar
      characterization.
AB  - A reversed-phase high-performance liquid chromatography-electrospray mass
      spectrometry (RP-HPLC-ESI-MS (ion trap)) method is developed, for the first time,
      for profiling transgenic and non-transgenic maize with the aim of cultivar
      characterization. To optimize chromatographic conditions the following parameters
      were studied: column, gradient, and ion-pairing reagent. Moreover, the influence
      in the MS signal of the variation of the capillary voltage and the accumulated
      ions in the trap was also studied. The developed method was applied to the
      profiling of different protein fractions (albumin, globulin, prolamin, and
      glutelin) isolated from Bt transgenic and non-transgenic maize cultivars.
      Moreover, different maize samples, namely, maize cultivars from different
      geographical origins (USA, Canada, France, and Spain), transgenic maize samples
      with certified GMO content, and three transgenic Bt maize cultivars with their
      isogenic non-transgenic counterparts (Aristis Bt vs. Aristis, PR33P67 vs.
      PR33P66, and DKC6575 vs. Tietar) were profiled by the developed method. Mass
      spectra obtained for certain peaks in the maize cultivars studied resulted, in
      some occasions, useful for cultivar characterization and differentiation. The
      comparison of UV and MS profiles and mass spectra corresponding to the protein
      fractions with those of the whole seeds enabled the assignment of some peaks.

PMID- 19748099
TI  - Pharmaceutical trace analysis in aqueous environmental matrices by liquid
      chromatography-ion trap tandem mass spectrometry.
AB  - An analytical method based on solid-phase extraction followed by liquid
      chromatography tandem mass spectrometry with an ion trap analyser was developed
      and validated for the quantification of a series of pharmaceutical compounds with
      distinct physical-chemical characteristics in estuarine water samples. Method
      detection limits were between 0.03 and 16.4 ng/L. The sensitivity and the
      accuracy obtained associated with the inherent confirmatory potential of ion trap
      tandem mass spectrometry (IT-MS/MS) validates its success as an environmental
      analysis tool. Two MS/MS transitions were used to confirm compound identity.
      Almost all pharmaceuticals were detected at ng/L level in at least one sampling
      site of the Douro River estuary, Portugal.

PMID- 19748100
TI  - Cation removal using cellulose chemically modified by a Schiff base procedure
      applying green principles.
AB  - Pentane-2,4-dione (acetylacetone) molecules were covalently incorporated under
      several different conditions to ethylene-1,2-diamine (en)-modified cellulose,
      using polar solvents or without solvents. The quantitative amount of en
      incorporated was given from 0.37+/-0.01 to 3.03+/-0.01 mmol of nitrogen per gram
      of cellulose, depending on the synthetic routes and after Schiff base formation
      this percentage was reduced by 1.38-6.12%. The synthetic routes indicated that
      lower solvent volumes produced higher amounts of en incorporation. However, the
      highest degree of pendant groups on the polymeric cellulose structure was
      obtained from a solvent-free reaction route. This procedure was applied for
      synthesizing all Schiff bases, causing a decrease in the amount of nitrogen. The
      available basic centers on the best covalently bonded biopolymer were
      investigated for adsorption of divalent copper, cobalt, nickel, and zinc from
      aqueous solution, with a capacity order of Cu2+ > Co2+ > Ni2+ > Zn2+.

PMID- 19748101
TI  - On the interfacial behavior of ionic liquids: surface tensions and contact
      angles.
AB  - In this work the liquid/vapour and the solid/liquid interfaces of a series of
      ionic liquids: 1-ethyl-3-methylpyridinium ethyl sulfate, [EMPy][EtSO4], 1-ethyl-3
      methylimidazolium ethyl sulfate, [EMIM][EtSO4], 1-ethanol-3-methylimidazolium
      tetrafluoroborate, [C2OHMIM][BF4], 1-butyl-3-methylimidazolium tetrafluoroborate,
      [BMIM][BF4], and 1-octyl-3-methylimidazolium tetrafluoroborate, [OMIM][BF4], were
      investigated. The surface tension was measured in a wide temperature range, (298
      453) K. The contact angles were determined on substrates of different polarities.
      Both on the polar (glass) and the non-polar substrates ((poly
      (tetrafluoroethylene) and poly-(ethylene)), the liquids with maximum and minimum
      surface tensions lead, respectively, to the highest and the lowest contact
      angles. The dispersive, gamma(L)(d), and non-dispersive, gamma(L)(nd), components
      of the liquid surface tension, gamma(L), were calculated from the contact angles
      on the non-polar substrates using the Fowkes approach. The polarity fraction,
      gamma(L)(nd)/gamma(L), was compared with the polarity parameter, k, obtained from
      the fitting of the surface tension vs. temperature data to the Eotvos equation.
      Good agreement was found for the extreme cases: [OMIM][BF4] exhibits the lowest
      polarity and [BMIM][BF4], the highest. When compared with the polarity fractions
      of standard liquids considered as "polar" liquids, the ionic liquids studied may
      be considered as moderately polar.

PMID- 19748102
TI  - Role of sensory information in the control of postural orientation in Parkinson's
      disease.
AB  - Clinical findings and experimental studies both in parkinsonian patients and on
      animal provide evidence that the control of the axial orientation is markedly
      impaired in Parkinson's disease (stooped posture, Camptocormia, Pisa syndrome).
      Nevertheless the postural orientation component in Parkinson's disease has been
      poorly investigated. One study reports that Parkinsonian patients present a major
      impairment of the postural orientation component in relation with a
      proprioceptive impairment. On the basis of these results, the visual dependence
      observed in Parkinsonian patients is re-defined as an adaptive strategy partly
      compensating for the impaired proprioception.

PMID- 19748103
TI  - Efficacy of a cooled bipolar epicardial radiofrequency ablation probe for
      creating transmural myocardial lesions.
AB  - OBJECTIVE: Creation of transmural myocardial lesions with epicardial surgical
      devices to treat atrial fibrillation is difficult. A new cooled bipolar
      radiofrequency ablation probe was used to create transmural myocardial lesions
      under controlled conditions. METHODS: The Coolrail (AtriCure, Inc, West Chester,
      Ohio) is a handheld probe with 2 parallel 30-mm long radiofrequency conductors.
      Conductors are cooled by water irrigation. Lesions were delivered to epicardial
      surface of isolated bovine myocardium sliced 3- to 8-mm thick, with blood flow
      beneath tissue at 0 or 0.4 m/s. Contact pressure between probe and tissue was
      either 450 g or 900 g. Tissue temperatures were measured. Tissue was sectioned
      every 5 mm along lesion long axis to determine lesion dimensions. RESULTS: For 80
      experiments with 450-g contact pressure, epicardial lesion length was 31.3 mm
      (interquartile range, 30.1-32.8 mm); endocardial lesion length was 14.1 mm
      (interquartile range, 0.0-22.6 mm). Average lesion depth was 4.2 +/- 0.74 mm.
      Temperature at probe interface was 81 degrees C +/- 21 degrees C; that at blood
      pool interface was 53 degrees C +/- 12 degrees C. Lesions were always transmural
      when tissue thickness was 4.0 mm or less. Endocardial blood flow did not
      influence lesion depth. With 900-g contact pressure, increased depth was always
      transmural at 4.8-mm tissue thickness or less. CONCLUSIONS: This irrigated
      bipolar radiofrequency probe consistently produced transmural lesions in tissue 4
      mm or thinner under controlled conditions in vitro. Lesion depth was increased by
      greater pressure on probe and not affected by blood flow. Endocardial lesions
      were smaller than epicardial dimensions.

PMID- 19748104
TI  - Effects of sudden stress due to heavy metal mercury on benthic foraminifer
      Rosalina leei: laboratory culture experiment.
AB  - Laboratory culture experiments were carried out to understand the response of
      benthic foraminifer Rosalina leei to gradual as well as sudden addition of heavy
      metal mercury into the media. When mercury was added suddenly, specimens did not
      show any change in morphology during the initial 40 days. However, later on, out
      of all the specimens subjected to mercury concentrations up to 150 ng/l, 75%
      developed deformities, whereas all the specimens subjected to 150-275 ng/l Hg
      concentrations, had deformed chambers. All specimens kept at 300 ng/l Hg
      concentration died within 20 days. In addition to this, irregularities were also
      observed in the rate of reproduction, number of juveniles produced and the
      survival rate of the juveniles. Where as in an earlier experiment where Hg
      concentration was increased gradually, irregularities in the newly added chambers
      were noticed only in case of specimens subjected to very high (180 ng/l) Hg
      concentration. However, during this experiment, growth was found to be inversely
      proportional to the mercury concentration.

PMID- 19748105
TI  - [Electrophysiological exploration of tunnel syndromes].
AB  - The compressive neuropathies often lead to segmental demyelination injury. These
      injuries can be detected using speed motor conduction and sensitivity conduction.
      The corresponding abnormalities are localized conduction abnormalities,
      presenting as deceleration or as a conductive block. Segmentary deceleration is
      perfectly well observed, such as in cases of carpal tunnel syndrome. The
      detection examination, recording motor unit potentials, can distinguish between a
      peripheral injury and a central injury as well as between a neurogenic injury and
      a myogenous injury. The precise study of the sensitivity potentials makes it
      possible to distinguish between a radicular injury, in which the sensitivity
      potentials are normal, and a plexus injury, in which the sensitivity potentials
      are altered because of a postganglionic injury.

PMID- 19748106
TI  - Conventional and ecological public health.
AB  - This paper suggests that current models of public health are no longer sufficient
      as a means for understanding the health challenges of the anthropogenic age, and
      argues for an alternative based upon an ecological model. The roots of this
      perspective originated within the Victorian era, although it found only limited
      expression at that time. Ecological thinking in public health has only been
      revived relatively recently. Derived from an analysis of obesity, this paper
      proposes the development of an approach to ecological public health based on four
      dimensions of existence: the material, the physiological, the social and the
      cultural-cognitive. The implications for public policy are considered.

PMID- 19748107
TI  - Relationship between evidence and policy: a case of evidence-based policy or
      policy-based evidence?
AB  - The use (or non-use) of evidence in health policy is an issue of growing interest
      and concern among both academic researchers and policy makers. Most public health
      research is government funded, yet the extent to which its findings are used to
      shape and inform policy is variable in the extreme. Part of the problem lies in
      the nature of the evidence itself and the extent to which it addresses the
      complexities of the issue being researched. However, part of it also lies in the
      way that evidence gets communicated and transmitted to those intended to benefit
      from, or act on, it. This paper reviews such matters and argues in favour of
      research that is more attuned to the needs of policy makers and practitioners. To
      achieve this, a paradigm shift is needed in the way in which research is produced
      and consumed. Rather than academics exclusively setting the agenda, a new
      approach to knowledge co-creation is overdue whereby researchers, and those they
      are seeking to address, work together to define the research questions, agree the
      methods, and assess the implications of the data analysis and findings for policy
      and practice.

PMID- 19748108
TI  - [Muscular botryomycosis in the rectus abdominis muscle: imaging findings].
AB  - Botryomycosis is a rare chronic suppurative granulomatous bacterial infection of
      the skin and viscera. It is classified into 2 groups: the visceral type and the
      cutaneous type, which can lead to involvement of contiguous muscle and bone, as
      appears probable in this case. We present a rare case of muscular botryomycosis
      in the rectus abdominis muscle in a patient with a history of abdominal wall
      surgery. Botryomycosis was initially mistaken for a soft-tissue tumor; after
      surgical resection it was diagnosed as muscular botryomycosis. We describe the
      clinical presentation and the imaging characteristics of this rare entity.

PMID- 19748109
TI  - [Clinical applications of computed tomography coronary angiography].
AB  - The clinical applications of computed tomography coronary angiography (CTCA) are
      constantly evolving. Initially employed to quantify coronary artery
      calcification, multidetector CT also makes it possible to evaluate the anatomy
      and anatomical variations of coronary circulation, rule out coronary disease, and
      follow up surgical and percutaneous revascularization procedures. Moreover, CTCA
      may potentially be useful to quantify ventricular function, characterize non
      calcified atherosclerotic plaques, and analyze myocardial perfusion and
      viability, providing anatomical, morphological, and functional information in
      patients with suspected ischemic heart disease.

PMID- 19748110
TI  - Assessment of the tumorigenesis and drug susceptibility of three new canine
      mammary tumor cell lines.
AB  - Three canine mammary tumor (CMT) cell lines, namely DE-E, DE-F and DE-SF, have
      been established from a surgically excised specimen of a malignant mammary tumor.
      These CMT cell lines have been cultured for over 200 passages. The cell doubling
      time was estimated to be approximately 30 h for all three cell lines. DE-E, DE-F
      and DE-SF were epithelial, fibroblast and spindle fibroblast in morphology,
      respectively. Under electron microscope, DE-F and DE-SF cells displayed a higher
      nucleus/cytoplasm ratio as compared with DE-E. Variation in chromosome number was
      also observed in the three cell lines. In addition to the morphological
      characteristics, these cell lines displayed differential patterns of several
      known mammary tumor cell markers. Following xenotransplantation of the CMT cells
      into nude mice, DE-F and DE-SF developed tumors within 2 weeks, whereas DE-E
      failed to develop any visible tumor up to 8 weeks after injection. Lastly, the
      CMT cell lines exhibited differential chemoresistance to several anti-tumor
      drugs, including melatonin, cyclosporine A, tamoxifen and indole, suggesting that
      these cell lines can be used as a comparative experimental model for the
      tumorigenesis of mammary carcinomas and a valuable tool for anti-cancer drug
      screening.

PMID- 19748111
TI  - Interactions between SIVNef, SIVGagPol and Alix correlate with viral replication
      and progression to AIDS in rhesus macaques.
AB  - Infection with Simian Immunodeficiency Virus (SIV) leads to high viral loads and
      progression to Simian AIDS (SAIDS) in rhesus macaques. The viral accessory
      protein Nef is required for this phenotype in monkeys as well as in HIV-infected
      humans. Previously, we determined that HIVNef binds HIVGagPol and Alix for
      optimal viral replication in cells. In this study, we demonstrated that these
      interactions could correlate with high viral loads leading to SAIDS in the
      infected host. By infecting rhesus macaques with a mutant SIV(mac239), where
      sequences in the nef gene that are required for these interactions were mutated,
      we observed robust viral replication and disease in two out of four monkeys,
      where they reverted to the wild type genotype and phenotype. These two rhesus
      macaques also died of SAIDS. Two other monkeys did not progress to disease and
      continued to harbor mutant nef sequences. We conclude that interactions between
      Nef, GagPol and Alix contribute to optimal viral replication and progression to
      disease in the infected host.

PMID- 19748112
TI  - Variation in half-life of penta-chlorodibenzofuran (PeCDF) blood level among
      Yusho patients.
AB  - Yusho (oil disease) is the name given to a food poisoning incident caused by rice
      bran oil that occurred in west Japan in 1968. The causative agents of Yusho are
      currently considered to be polychlorinated biphenyls (PCBs) and their by
      products, such as dioxin like compounds. The levels of 2,3,4,7,8-penta
      cholorodibenzofuran (PeCDF) are measured in the blood of Yusho patients who
      attend medical check-ups. The objectives of this study were to determine the half
      life of PeCDF in these patients. Linear regression analysis was performed with
      the binary logarithm of PeCDF blood levels in Yusho patients as the dependent
      variable and the measurement year as the independent variable. The linear
      coefficient determined in this analysis is the reciprocal of the half-life. The
      half-life of PeCDF varied among patients. Among patients with PeCDF blood levels
      of 50pgg(-1) or higher, there were two groups: one showing a half-life of
      approximately 7 years and the other showing no reduction in PeCDF levels over
      time. The results indicate that there is a group of patients whose PeCDF levels
      are maintained at a high level. Our study suggests that a more complicated model
      is required to explain PeCDF excretion in humans.

PMID- 19748113
TI  - Batch experiments versus soil pore water extraction--what makes the difference in
      isoproturon (bio-)availability?
AB  - Two approaches to determine pesticide (bio-)availability in soils (i) batch
      experiments with "extraction with an excess of water" (EEW) and (ii) the recently
      introduced "soil pore water (PW) extraction" of pesticide incubated soil samples
      have been compared with regard to the sorption behavior of the model compound
      isoproturon in soils. A significant correlation between TOC and adsorbed
      pesticide amount was found when using the EEW approach. In contrast, there was no
      correlation between TOC and adsorbed isoproturon when using the in situ PW
      extraction method. Furthermore, sorption was higher at all concentrations in the
      EEW method when comparing the distribution coefficients (K(d)) for both methods.
      Over all, sorption in incubated soil samples at an identical water tension (-15
      kPa) and soil density (1.3 g cm(-3)) appears to be controlled by a complex
      combination of sorption driving soil parameters. Isoproturon bioavailability was
      found to be governed in different soils by binding strength and availability of
      sorption sites as well as water content, whereas the dominance of either one of
      these factors seems to depend on the individual composition and characteristics
      of the respective soil sample. Using multiple linear regression analysis we
      obtained furthermore indications that the soil pore structure is affected by the
      EEW method due to disaggregation, resulting in a higher availability of pesticide
      sorption sites than in undisturbed soil samples. Therefore, it can be concluded
      that isoproturon sorption is overestimated when using the EEW method, which
      should be taken into account when using data from this approach or similar batch
      techniques for risk assessment analysis.

PMID- 19748114
TI  - Plasma PGF 2 alpha metabolite levels in cats with uterine disease.
AB  - Uterine disease induces PGF(2 alpha) increase in many animal species, which can
      be measured by the metabolite 15-keto-(13,14)-dihydro-PGF(2 alpha) (PGFM). Plasma
      PGFM levels are associated with severity of the uterine disease and presence of
      systemic inflammatory response syndrome (SIRS) in dogs. The objectives in this
      study were to investigate PGFM levels, presence of SIRS, and clinical and
      laboratory parameters in female cats as possible indicators for severity of
      uterine disease. In total, 7 female cats with pyometra, 2 with mucometra, 7 with
      cystic endometrial hyperplasia (CEH), and 14 healthy control cats were included.
      Physical examination, ovariohysterectomy, and histopathology were performed,
      laboratory parameters were analyzed, and PGFM levels were analyzed by
      radioimmunoassay. Analysis of variance, Fisher's exact test, Student's t-test and
      Pearson's product moment correlation coefficient were used for data analysis. In
      cats with pyometra, mean PGFM levels were increased (21.1 nmol L(-1)) but were
      decreased in cats with CEH (0.4 nmol L(-1)) compared with control cats (0.6 nmol
      L(-1)). In cats with mucometra, the mean PGFM level was 8.8 nmol L(-1). Systemic
      inflammatory response syndrome was present in 6 (85%) cats with pyometra, 1 cat
      with mucometra, and 1 cat with CEH. Hospitalization length was negatively
      correlated with albumin and positively correlated with total white blood cell
      count (WBC), neutrophils, band neutrophils (BN), percentage BN (PBN), and
      monocytes. Pyometra and mucometra were associated with increased plasma levels of
      PGFM. The parameters albumin, WBC, neutrophils, BN, PBN, and monocytes may be
      useful to determine morbidity as measured by hospitalization length.

PMID- 19748115
TI  - Comparison of edge chipping resistance of PFM and veneered zirconia specimens.
AB  - OBJECTIVES: To investigate the chipping resistance of veneered zirconia specimens
      and compare it to the chipping resistance of porcelain fused to metal (PFM)
      specimens. METHODS: Veneered zirconia and PFM bar specimens were prepared in
      clinically relevant thicknesses. The specimen edges were chipped with different
      magnitude forces, producing chips of various sizes. The range of sizes included
      small chips that did not penetrate all the way through the veneers to the
      substrates, and also chips that were very large and reached the zirconia or metal
      substrates. The relationship between force magnitude and chip size (edge
      distance) was graphed. The resulting curves were compared for the veneered
      zirconia and PFM specimens. Knoop hardness vs. force graphs for the veneers and
      substrates were also obtained. RESULTS: The zirconia and PFM veneer chipping data
      followed a power law (coefficient of determination, R(2)>0.93) as expected from
      the literature. The curves overlapped within the combined data scatter,
      indicating similar resistance to chipping. The chips made in both types of
      specimens detached and did not penetrate into the substrate when they reached the
      veneer/substrate intersections. The hardness-load curves for the veneers and
      substrates all exhibited an indentation size effect (ISE) at low loads. The Knoop
      hardness values with uncertainties of +/-one standard deviation at 4N loads for
      the metal, zirconia, and the metal and zirconia veneers are: (2.02+/-0.08,
      12.01+/-0.39, 4.24+/-0.16 and 4.36+/-0.02GPa), respectively, with no
      statistically significant difference between the veneers (Tukey pairwise
      comparison at 0.95 family confidence). SIGNIFICANCE: This work indicates that a
      similar resistance to chipping might be expected for veneered zirconia and PFM
      restorations, in spite of the large difference in substrate hardness. Differences
      in susceptibility to chip spalling were not detected, but the chips in both
      specimen types detached off the sides in a similar manner instead of extending
      into the substrates.

PMID- 19748116
TI  - Levels and trends in under-5 mortality, 1990-2008.

PMID- 19748117
TI  - Extracellular NAD(+) induces a rise in [Ca(2+)](i) in activated human monocytes
      via engagement of P2Y(1) and P2Y(11) receptors.
AB  - Extracellular nicotinamide adenine dinucleotide (NAD(+)) is known to increase the
      intracellular calcium concentration [Ca(2+)](i) in different cell types and by
      various mechanisms. Here we show that NAD(+) triggers a transient rise in
      [Ca(2+)](i) in human monocytes activated with lipopolysaccharide (LPS), which is
      caused by a release of Ca(2+) from IP(3)-responsive intracellular stores and an
      influx of extracellular Ca(2+). By the use of P2 receptor-selective agonists and
      antagonists we demonstrate that P2 receptors play a role in the NAD(+)-induced
      calcium response in activated monocytes. Of the two subclasses of P2 receptors
      (P2X and P2Y) the P2Y receptors were considered the most likely candidates, since
      they share calcium signaling properties with NAD(+). The identification of P2Y(1)
      and P2Y(11) as receptor subtypes responsible for the NAD(+)-triggered increase in
      [Ca(2+)](i) was supported by several lines of evidence. First, specific P2Y(1)
      and P2Y(11) receptor antagonists inhibited the NAD(+)-induced increase in
      [Ca(2+)](i). Second, NAD(+) was shown to potently induce calcium signals in cells
      transfected with either subtype, whereas untransfected cells were unresponsive.
      Third, NAD(+) caused an increase in [cAMP](i), prevented by the P2Y(11) receptor
      specific antagonist NF157.

PMID- 19748118
TI  - NPY regulation of bone remodelling.
AB  - Neuropeptide Y (NPY), a classic neuronal regulator of energy homeostasis, is now
      also known to be involved in the control of bone homeostasis. Of the five known Y
      receptors through which the NPY family of ligands signals, the Y1 and Y2
      receptors have so far been implicated in the control of osteoblast activity and
      thus bone formation. Analysis of brain specific NPY overexpressing and Y receptor
      knockout models has revealed a powerful anabolic pathway likely involving
      hypothalamic Y2 receptors and osteoblastic Y1 receptors. Furthering our
      understanding of the mechanisms underlying the involvement of the NPY system in
      the control of bone could lead to the development of therapies to improve bone
      mass in patients with diseases such as osteoporosis.

PMID- 19748119
TI  - Primary autoimmune myelofibrosis in a 36-year-old patient presenting with
      isolated extreme anemia.

PMID- 19748120
TI  - The impact of an additional ecotoxicity test on ecological quality standards.
AB  - The present study aims to support decisions on whether or not to perform an extra
      toxicity test in order to improve environmental quality standards (EQSs). The
      impact of an additional ecotoxicity test was analyzed by predicting new
      ecotoxicity values with three different estimation methods and adding them to
      existing species sensitivity distributions (SSDs) on which the EQSs are based.
      The results show that EQSs are likely to increase due to increasing sample size,
      but the change also depends on the number of toxicity values available, the
      estimation method used and the representativeness of the species tested. The
      management consequences are illustrated in a case study on contaminated
      freshwater sediment in the Netherlands. It is shown that a slight increase of the
      EQS can result in a large reduction of sediment remediation costs without
      impairing regulatory protection levels. The paper identifies indicators that can
      be used to evaluate the potential impact of an extra ecotoxicity test.

PMID- 19748121
TI  - Toxicological responses in wheat Triticum aestivum under joint stress of
      chlorimuron-ethyl and copper.
AB  - It was observed in this work that joint effects of chlorimuron-ethyl and copper
      on chlorophyll content, the peroxidases (POD) activity, superoxide dismutases
      (SOD) activity and soluble protein content in leaves and roots of wheat were
      markedly significant. The chlorophyll content and the SOD activity in wheat under
      joint stress of chlorimuron-ethyl and copper were obviously higher than that
      under single stress of chlorimuron-ethyl. However, joint effect of chlorimuron
      ethyl and copper on the decrease of soluble protein content in roots was more
      serious than that under single stress of chlorimuron-ethyl. The effect of copper
      dominated the change of POD activity and soluble content in leaves and roots of
      wheat under joint stress of chlorimuron-ethyl and copper. It was suggested that
      the change of enzyme activity was related to the change of soluble protein
      content in roots under single and joint stress of chlorimuron-ethyl and copper.

PMID- 19748122
TI  - [Phosphorus magnetic resonance spectroscopy: Brain pathologies applications].
AB  - Until recent years, brain applications of (31)P magnetic resonance spectroscopy
      were poor. Arising of clinical high field strength magnets (three Tesla) as well
      as dedicated brain coils (eg: bird cage), using specific and useful sequences
      providing appropriate spatial localisation and signal to noise ratio brought
      highlights on multinuclear spectroscopy. Better understanding of brain metabolism
      emphasizes the role of phosphoenergetic compounds and its potential issues in
      tumoral, metabolic and degenerative diseases. In the present paper, we report 1
      year of experience and preliminary results for 40 patients as well as review of
      the literature. By successive in vivo determination and quantitation of numerous
      metabolites it allows, multinuclear spectroscopy may provide additional
      information to biomathematical models of brain metabolism.

PMID- 19748123
TI  - PPARalpha ligands cause lymphocyte depletion and cell cycle block and this is
      associated with augmented TRB3 and reduced Cyclin B1 expression.
AB  - PPARalpha ligands are medications used clinically to prevent cardiovascular
      events, however studies have shown that these agents are also anti-inflammatory.
      Our previous studies have shown that PPARalpha ligands induce lymphocyte
      depletion. PPARalpha ligands also potently upregulate TRB3, a protein that has
      been associated with cell cycle arrest. Therefore the following studies were
      undertaken to determine the mechanisms associated with lymphocyte depletion. Our
      studies demonstrate that WY14,643, a PPARalpha ligand, decreases the amount of
      lymphocytes recovered after stimulation and reduces cellular divisions. Cells
      treated with WY14,643 also accumulate in the G2/S phase of the cell cycle. TRB3
      has been shown to inhibit the phosphorylation of AKT/Protein Kinase B, and
      reduced activation of AKT has been associated with decreased cellular divisions
      and survival. However in lymphocytes, TRB3 did not reduce the phosphorylation of
      AKT, and WY14,643 treatment was associated with enhanced activation of AKT.
      Drosophila tribbles (TRB3 homolog) causes G2 arrest by decreasing the expression
      of a Cdc25c homolog. Lymphocytes stimulated and treated with WY14,643 have
      reduced expression of Cdc25c, however this is not associated with enhanced
      expression of phosphorylated-Cdc2 which induces G2 arrest. Instead we observed
      that WY14,643 consistently reduces the protein and mRNA expression of Cyclin B1.
      Moreover, TRB3 inhibits activation of a Cyclin B1 promoter construct. In summary,
      we propose that PPARalpha ligands may reduce cellular number by augmenting TRB3
      expression, which in turn induces cell cycle arrest by reducing the expression of
      Cyclin B1. Reduced cellular divisions and cell cycle arrest may be responsible
      for some of the immunomodulatory effects of these agents that have been
      consistently observed in human trials.

PMID- 19748124
TI  - Calreticulin maintains the low threshold of peptide required for efficient
      antigen presentation.
AB  - Calreticulin (CRT) plays a critical role in MHC class I antigen processing and
      elicits peptide-specific CD8(+) T cell responses against tumours when
      administered with peptides. However, how CRT contributes to class I antigen
      processing and the mechanism of its adjuvant effect in anti-tumour responses,
      remain to be elucidated. Here we show that reduced class I expression in CRT
      deficient cells can be restored by the direct delivery of peptides into the ER or
      by incubation at low temperature. CRT deficient cells exhibited a TAP-deficient
      phenotype in terms of class I assembly, without loss of TAP expression or
      functionality. Furthermore, a higher concentration of antigen in the cytosol is
      required for specific T cell stimulation, suggesting that CRT has a functional
      role in the maintenance of the low peptide concentration threshold required in
      the ER for efficient antigen presentation. In the absence of CRT, ERp57 is up
      regulated, which indicates that they collaborate with each other in class I
      antigen processing.

PMID- 19748125
TI  - Crystal structure and properties of the copper(II) complex of sodium monensin A.
AB  - The preparation and structural characterization of a new copper(II) complex of
      the polyether ionophorous antibiotic sodium monensin A (MonNa) are described.
      Sodium monensin A binds Cu(II) to produce a heterometallic complex of composition
      [Cu(MonNa)(2)Cl(2)].H(2)O, 1. The crystallographic data of 1 show that the
      complex crystallizes in monoclinic space group C2 with Cu(II) ion adopting a
      distorted square-planar geometry. Copper(II) coordinates two anionic sodium
      monensin ligands and two chloride anions producing a neutral compound. The sodium
      ion remains in the inner cavity of the ligand retaining its sixfold coordination
      with oxygen atoms. Replacement of crystallization water by acetonitrile is
      observed in the crystal structure of the complex 1. Copper(I) salt of the methyl
      ester of MonNa, 2, was identified by X-ray crystallography as a side product of
      the reaction of MonNa with Cu(II). Compound 2, [Me-MonNa][H-MonNa][CuCl(2)]Cl,
      crystallizes in monoclinic space group C2 with the same coordination pattern of
      the sodium cation but contains a chlorocuprate(I) counter [CuCl(2)](-), which is
      linear and not coordinated by sodium monensin A. The antibacterial and
      antioxidant properties as two independent activities of 1 were studied. Compound
      1 is effective against aerobic Gram(+)-microorganisms Bacillus subtilis, Bacillus
      mycoides and Sarcina lutea. Complex 1 shows SOD-like activity comparable with
      that of the copper(II) ion.

PMID- 19748126
TI  - Combined chelation based on glycosyl-mono- and bis-hydroxypyridinones for
      aluminium mobilization: solution and biodistribution studies.
AB  - Taking into account the recognized interest of a poly-pharmacological strategy in
      chelation therapy, a study of aluminium combined chelation based on 3-hydroxy-4
      pyridinone (3,4-HP) compounds with complementary properties, associated to
      different denticity, size and extrafunctionality, is presented herein. In
      particular, Al-chelation has been explored, using a tetradentate IDA bis-(3,4-HP)
      ligand, L, and two N-glycosyl mono-(3,4-HP) derivatives (A or B). Combined
      complexation studies with the tetradentate and the most promising bidentate
      ligand (A) evidenced the formation of ternary complexes with high thermodynamic
      stability (Al-L-A) being the predominant species at physiological pH. In vivo
      studies on the ability for radiotracer ((67)Ga) removal from loaded mice, as a
      model of aluminium accumulation in body, have shown that the simultaneous
      administration to (67)Ga-loaded mice of a mono- and a bis-(3,4-HP) chelator (e.g.
      A and L) leads to a rapid metal elimination from main organs and whole animal
      model. This may be rationalized by coadjuvation and eventual synergistic effects,
      due to complementary accessibility of the chelators to different cellular
      compartments.

PMID- 19748127
TI  - Directly observed hydrogen bonds at calcium-binding-sites of calmodulin in
      solution relate to affinity of the calcium-binding.
AB  - Molecular tuning to calcium-binding in the EF-hand motif of holo-calmodulin was
      studied in solution by NMR (h3)J(NC') H-bond couplings. In the N-terminus lobe of
      holo-calmodulin, the glutamate crucial for Ca(2+) coordination has network of H
      bonds weaker than inferred from the X-ray crystal structure. This glutamate at
      position 12 appears shifted away from the Ca(2+) preferred coordination, which
      can explain the lower affinity of the calcium-binding to the N-terminus with
      respect to C-terminus EF hands.

PMID- 19748128
TI  - Assessment of soil aluminium pools along three mountainous elevation gradients.
AB  - Anthropogenic soil acidification in mountain forests and consequent Al release
      still present a significant problem in many regions. The effect of deposition may
      differ according to stand conditions, including altitude. This contribution is
      focused on three elevation transects, two in the Jizera Mountains strongly
      influenced by acid deposition, one in the less affected Novohradske Mountains.
      Quantification of pools of different Al forms and related soil characteristics
      (organic carbon, exchangeable hydrogen cations, sorption characteristics, etc.)
      is evaluated. In the Novohradske Mountains, the pool of both organically bound
      and water-soluble Al increases with increasing altitudes. In the Jizera
      Mountains, the distribution is more complicated; it is strongly affected by
      different forest type (beech vs. spruce), deforestation, and other local
      differences. Higher amounts of Al are bound in the mineral horizons compared to
      the surface organic horizons, even in the case of organically bound Al pools.
      Further differences between different altitudes and between soil horizons in Al
      distribution were revealed by detailed Al speciation using HPLC/IC method.

PMID- 19748129
TI  - Comparison of Al speciation and other soil characteristics between meadow, young
      forest and old forest stands.
AB  - The aim of this paper is to describe the influence of spruce (Picea abies)
      afforestation on soil chemical properties, especially on soil acidity and
      aluminium (Al) mobilization and speciation in soil. For our study we used a
      unique set of three adjacent plots, including a meadow and two spruce forest
      stands of different age, in otherwise comparable conditions. The plots were
      located in the region of Giant Mountains, north-eastern Czech Republic. In
      general, pH values decreased and Al concentrations increased significantly after
      afforestation. Speciation of KCl-extractable and water-soluble Al in soil samples
      was done by means of HPLC/IC method. The concentrations of Al(X)(1+) and
      Al(Y)(2+) forms (in both extracts) are higher in humic and organically enriched
      (Bhs) horizons. The highest concentration of Al(3+) in both extracts is in the B
      horizons of old forest. Generally, in all studied stands majority of Al in
      aqueous extract is in the Al(X)(1+) form, which indicates that a large amount of
      mobile Al is bound in organic complexes. It suggests that actual toxicity is
      rather low. On the other hand, we have proved that majority of KCl-extractable Al
      exists in Al(3+) form. Thus we can conclude that disturbance of existing
      equilibrium may cause massive release of highly toxic Al(3+) from soil sorption
      complex to the soil solution, and consequently it can endanger the whole
      ecosystem. Moreover, continuous soil acidification accelerated by anthropogenic
      factors leading to Al mobilization represents a chemical time bomb.

PMID- 19748130
TI  - Does a psychoeducational approach reach targeted patients with bipolar disorder?
AB  - OBJECTIVES: The goal of this paper was to determine factors which are related to
      motivation of bipolar patients to attend a psychoeducation program. METHODS:
      Patients with bipolar disorder which had at least four years of prospective
      follow-ups were invited to a 6-week psychoeducation program. Patients who
      accepted and those who refused the participation were compared using several
      clinical characteristics. RESULTS: Of the 173 patients who were invited, 84
      participated in the program. Participants had significantly more family history
      of bipolar disorder and suicide, good response to prophylactic treatment, full
      medication adherence, therapeutic blood levels of mood stabilizers, regular
      follow-up visits, mixed episodes, and significantly less total number of
      episodes. Presence of mixed episodes, full medication adherence and therapeutic
      blood level of mood stabilizers were found predictive for attendance in logistic
      regression analysis. CONCLUSIONS: Our results suggest motivation and
      participation rates of patients who attended a psychoeducation program were
      constrained. Factors associated with a poor response to psychopharmacologic
      treatments also seem valid for non-attendance to the psychological interventions.

PMID- 19748131
TI  - Associations between betel nut (Areca catechu) and symptoms of schizophrenia
      among patients in Nepal: A longitudinal study.
AB  - Betel nut is one of the mostly widely used substances in the world, particularly
      across Asia. Arecoline, a partial muscarinic agonist, has been hypothesized to
      have beneficial effects on both positive and negative symptoms of schizophrenia.
      This study aims to further explore associations between betel use and symptoms of
      schizophrenia in a 4-month longitudinal study in Nepal. Sixty Nepali patients
      with schizophrenia were recruited from regional outpatient clinics. The Positive
      and Negative Syndrome Scale (PANSS) and the Social Adaptation Self-Evaluation
      Scale were used to assess symptoms and social functioning in regular betel users
      and non-users. No significant group differences or dose-response relationships
      were noted on either initial or follow-up assessments. Stratifying by sex also
      failed to reveal an association between symptoms and betel use, which stands in
      contrast with previously reported data from Micronesia. There were no differences
      seen in social functioning other than a significantly higher proportion of betel
      users holding jobs. It was also noted that significantly fewer betel chewers were
      taking anti-cholinergic medication, which may tentatively indicate a potentially
      therapeutic role in the future for partial muscarinic agonists in the treatment
      of medication-induced movement disorders.

PMID- 19748132
TI  - The P300 as a possible endophenotype for schizophrenia and bipolar disorder:
      Evidence from twin and patient studies.
AB  - It has been proposed that psychophysiological abnormalities in schizophrenia,
      such as decreased amplitude of the evoked potential component P300, may be
      genetically influenced. Studies of heritability of the P300 have used different
      and typically more complex tasks than those used in clinical studies of
      schizophrenia. Here we present data on P300 parameters on the same set of
      auditory and visual tasks in samples of twins, and patients with schizophrenia or
      bipolar disorder to examine the P300 as a possible endophenotype. Evidence from
      the twin study indicated that the auditory, but not visual, P300 amplitude is
      genetically influenced at centro-parietal sites. Similarly, auditory and to a
      lesser extent visual P300 amplitude were decreased in schizophrenia and bipolar
      disorder. Results indicate that the auditory P300 may serve as an endophenotype
      for schizophrenia. However, given that schizophrenia and bipolar disorder
      patients could not be distinguished on these measures at midline sites, it
      appears that the P300 may be a marker for functional psychosis in general rather
      than being specific to schizophrenia.

PMID- 19748133
TI  - Differential expression of toll-like receptor mRNA in selected tissues of goat
      (Capra hircus).
AB  - Pattern recognition receptors (PRRs) expressed by various immune cells and
      tissues have been shown to play a pivotal role in the recognition of pathogens by
      the host. The present study was carried out to identify toll-like receptors
      (TLRs) 1-10 mRNA in goat peripheral blood mononuclear cells (PBMCs) and selected
      tissues including jejunum, lung, lymph node, skin, spleen and uterus using
      reverse transcriptase polymerase chain reaction (RT-PCR). Our results confirm
      earlier reports regarding the evolutionarily conserved nature of these receptors
      as successful amplification of the goat TLR mRNAs could be obtained with bovine
      TLR mRNA-specific primers. The partial sequences of the purified TLR PCR
      amplicons had 93.8-99.7% nucleotide identity with sheep TLR cDNA sequences
      available in the GenBank. Semi-quantification of the expression levels of the TLR
      mRNAs was done using densitometric analysis of band intensities. All the TLR
      mRNAs (1-10) were expressed in high amounts in the lymph node while spleen showed
      lower expression of TLR 6 and 10 mRNAs. PBMC and lung expressed all TLR mRNAs in
      high amounts except TLR 10 mRNA. In uterus and jejunum, lower expression of TLR
      3, 4 and 10 mRNAs was seen. Skin had the lowest repertoire of TLR mRNA expression
      with lower or no expression of TLR 2, 3, 4, 8, 9 and 10 mRNAs. Another
      interesting observation was that tissues such as uterus, lung and skin that
      exhibited lower levels of TLR 2 had higher levels of TLR 6 mRNAs.

PMID- 19748134
TI  - Inhibition of experimental autoimmune uveitis by amino acid copolymers.
AB  - Glatiramer acetate (GA), a synthetic random amino acid copolymer, poly(Y, E, A,
      K)n, is widely used for treatment of multiple sclerosis. It inhibits experimental
      autoimmune encephalomyelitis (EAE) in mice by competition with the antigen and by
      induction of regulatory T cells. A novel copolymer, poly (F, Y, A, K)n ,
      designated FYAK, was more effective than GA in its immunomodulatory activity in
      EAE. Here, FYAK and GA were compared in the amelioration of another disease model
      in mice, experimental autoimmune uveoretinitis (EAU). When tested by co
      immunization with an uveitogenic antigen, FYAK was superior to GA in its capacity
      to inhibit EAU induction, as well as immune processes related to this condition.
      Further, regulatory T-cell lines specific to FYAK were more immunosuppressive
      than GA-specific lines in the EAU model. The superiority of FYAK-specific lines
      was accompanied by higher production of Th2 cytokines. These data thus
      demonstrate that FYAK, a novel copolymer, is superior to GA in its capacity to
      inhibit immunopathogenic processes in a non-central nervous system tissue.

PMID- 19748135
TI  - Outpatient administration of radioactive iodine after total thyroidectomy for
      pediatric thyroid cancer: a report of three cases.
AB  - Radioactive iodine is used as an anti-cancer reagent for papillary and follicular
      thyroid carcinomas. Patients that are administered a large dose of radioactive
      iodine are required to stay alone in an isolated room for several days. Some
      young children with thyroid carcinoma who cannot take care of themselves are not
      able to undergo this therapy. We tried outpatient administration of (131)I for
      these patients. In Japan, administration for outpatients is restricted to 500 MBq
      (13.5 mCi). We administrated 13 mCi (131)I to three patients suffering from
      pediatric thyroid carcinomas. One patient with recurrent follicular carcinoma in
      the neck showed complete loss of the thyroid bed and an undetectable level of
      serum thyroglobulin 7 months after the first administration of (131)I, and no
      further recurrence was observed after 5 years. Another patient with multiple lung
      metastases showed weakened uptake of (131)I in the lung and an evident decrease
      in serum thyroglobulin after administration. However, the last patient with lung
      metastases with a low (131)I uptake showed no evident change in either (131)I
      uptake in the lung nor the serum thyroglobulin level. Administration of 13 mCi
      (131)I was effective in two of three patients. Thus, it is worth considering this
      therapy as a practical option for pediatric thyroid carcinoma in the countries in
      which outpatient administration of a large dose of (131)I is restricted.

PMID- 19748136
TI  - Cadmium in three marine phytoplankton: accumulation, subcellular fate and thiol
      induction.
AB  - We explored the possible mechanisms leading to differential Cd sensitivity in
      three marine phytoplankton (the diatom Thalassiosira pseudonana, the
      dinoflagellate Prorocentrum minimum and the green alga Chlorella autotrophica)
      based on their Cd accumulation, Cd subcellular distribution, and phytochelatin
      (PC) synthesis. The most sensitive species, T. pseudonana, generally exhibited
      the highest Cd body burden and organelle (org)-Cd concentration. C. autotrophica,
      the most tolerant species to Cd, had the smallest org-Cd accumulation, as well as
      a much higher percentage of cellular debris-Cd, which may play an important role
      in Cd detoxification. The dinoflagellate P. minimum, with a sensitivity between
      the diatoms and green algae, had a comparable Cd body burden but higher
      percentage of org-Cd than C. autotrophica. Although the induction of PCs was
      dependent on the species, the intracellular (intra)-Cd/PC-SH ratio showed a
      strong linear log-log relationship with [Cd(2+)], suggesting that this ratio
      could possibly be a biomarker for environmental [Cd(2+)] stress. With the
      increases of the intra-Cd/PC-SH ratio, these three species of phytoplankton
      exhibited clearly different patterns of growth inhibition, implying that the
      effectiveness of PCs as a detoxification pathway is dependent on the species. The
      lowest intra-Cd/PC-SH toxicity threshold for T. pseudonana implied its low PC-Cd
      capacity. Furthermore, the sudden slowdown of growth inhibition when the intra
      Cd/PC-SH ratio reached 33 implied the launch of other detoxification pathway in
      C. autotrophica in order to alleviate Cd toxicity. Our study demonstrated that
      accumulation and subcellular distribution of Cd and PC synthesis can account for
      the inter-species differences in Cd sensitivity in marine phytoplankton.

PMID- 19748137
TI  - Prevalence of transradial coronary angiography and intervention in China: report
      from the Transradial coronary intervention Registration Investigation in China
      (TRI-China).
AB  - OBJECTIVE: To investigate the prevalence of TRA and TRI in China in the years
      2006 and 2007. METHOD: About 400 TRI-China questionnaires were sent to hospitals
      all over China from February to May in 2007 and 2008. RESULTS: Data was collected
      from 163 and 111 hospitals all over China in the year 2006 and 2007,
      respectively. A total of 108,658 CAG and 45,176 PCI cases in 2006 and 115,124 CAG
      and 48,379 PCI cases in 2007 were enrolled in the study. There were more TRA and
      TRI in 2007 than 2006 (TRA, 60.23% vs. 47.84%, p<0.001; TRI, 56.28%vs. 44.69%,
      p<0.001). Judkin's and MP (multipurpose) were the major catheter types during TRA
      in 2006 and 2007 (Judkin's, 47.62% vs. 40.52%; MP, 41.23% vs. 40.38%). TRI could
      be completed through 6 French GC in the majority of cases (85.49% in 2006 vs.
      93.13% in 2007). Unfractionated heparin (UFH) was the major anticoagulant during
      TRA and TRI (88.76% in 2006 vs. 99.10% in 2007,). Nitroglycerine (NTG) was the
      major vasodilator to prevent radial artery spasm (75.80% in 2006 vs. 92.79% in
      2007). CONCLUSION: Transradial approach has become the primary access of CAG and
      PCI in China.

PMID- 19748138
TI  - Lack of effect of perhexiline in ischaemic heart failure.

PMID- 19748139
TI  - Traditional descriptive analysis and novel visual representation of diagnostic
      repeatability and reproducibility: application to an infectious salmon anaemia
      virus RT-PCR assay.
AB  - As a component of diagnostic test evaluation, the estimation of repeatability and
      reproducibility of an assay is necessary to assess the robustness and the
      transferability of the method among laboratories. Respectively defined as the
      agreement within and between laboratories, repeatability and reproducibility of a
      qualitative diagnostic test are traditionally reported using observed proportion
      of agreement or Kappa values. Applied to a recently designed RT-PCR assay for the
      detection of infectious salmon anaemia virus, repeatability only within a
      national reference laboratory and reproducibility with two additional independent
      regional laboratories were investigated. Homogenization of fish kidney tissue was
      conducted to potentially provide more uniform submission material, and to assess
      the effect of homogenization on laboratory comparability. Comparison of agreement
      between non-homogenized and homogenized tissue samples revealed different
      patterns of test results and unexpected alterations of agreement due to
      homogenization. This observation may be explained by cross-contamination of some
      samples during the homogenization process. One of the laboratories was in clear
      disagreement with the two others and impacted the overall reproducibility of the
      assay. Agreement levels were visually described using a novel tree-shape
      representation inspired from phylogenetic studies. The resulting phylogram
      illustrated the proximity of test findings between repeated samples within a
      laboratory and between laboratories, and facilitated the interpretation of the
      agreement levels.

PMID- 19748140
TI  - Do increased premium subsidies affect how much health insurance is purchased?
      Evidence from the self-employed.
AB  - This paper estimates the effect of recent federal and state level increases in
      the deductibility of health insurance premiums for self-employed individuals,
      which reduced the after-tax price of health insurance, on both the take-up of
      coverage and the amount of insurance purchased. Using a panel of tax returns
      filed by self-employed taxpayers from 1999 to 2004, we estimate a take-up
      elasticity of -0.316 overall, with significantly higher elasticities for single
      taxpayers. On the intensive margin, we find an elasticity of -0.733 overall.

PMID- 19748141
TI  - Twinning partnerships through International Atomic Energy Agency (IAEA) to
      improve radiotherapy in common paediatric cancers in low- and mid-income
      countries.
AB  - PURPOSE: The article summarises the current use of radiotherapy (RT) in childhood
      cancer and suggests methods to improve current practice in regions where outcomes
      of paediatric cancer patients are inferior to those of high-income countries.
      METHODS AND MATERIALS: The International Atomic Energy Agency (IAEA) is
      supporting low- and mid-income countries (LMICs) in upgrading cancer care where
      nuclear applications, particularly RT, are used. A consensus meeting of experts
      was invited to advise IAEA on the needs for RT in paediatric cancer patients. The
      current indications for RT were reviewed, together with regional differences in
      access, practice and outcome. RESULTS: Regional variations in the use of evidence
      based multidisciplinary care including RT were associated with varying outcomes
      of paediatric cancer patients. The contribution of modern and investigational
      technology to these differences is uncertain and should be determined in clinical
      trials. Adequate resources are required to support children through the acute
      phase of treatment and to permit early recognition and management of late
      effects. An IAEA sponsored project for prospective data collection to assess the
      current and future status of radiation treatment in childhood cancer in LMICs has
      commenced. CONCLUSION: RT remains an essential component of the multidisciplinary
      management of many paediatric cancers. Excessive variations in outcome are
      inappropriate and call for action on harmonising training programmes and
      compliance with evidence-based recommendations. Training projects targeting
      paediatric cancer care are being implemented and clinical studies comparing new
      technologies against evidence-based approaches are needed to achieve this goal.
      The IAEA has an important role in these activities and has commenced prospective
      data collection in 13 LMICs to monitor trends in treatment techniques and
      outcomes.

PMID- 19748142
TI  - Re: "The safety and efficacy of robotic image-guided radiosurgery system
      treatment for intra- and extracranial lesions: a systematic review of the
      literature" [Radiotherapy and Oncology 89 (2009) 245-253].

PMID- 19748143
TI  - MRI before and after external beam intensity-modulated radiotherapy of patients
      with prostate cancer: the feasibility of monitoring of radiation-induced tissue
      changes using a dynamic contrast-enhanced inversion-prepared dual-contrast
      gradient echo sequence.
AB  - PURPOSE: To identify and quantify suitable pharmacokinetic MRI parameters for
      monitoring tissue changes after external beam intensity-modulated radiotherapy of
      prostate cancer. MATERIAL AND METHODS: Six patients with biopsy-proven prostate
      cancer (initial PSA, 6.0-81.4 ng/ml) underwent MRI at 1.5 T using a combined
      endorectal/body phased-array coil and a dynamic contrast-enhanced inversion
      prepared dual-contrast gradient echo sequence (T1/T2(*)w; 1.65 s temporal
      resolution). MRI was performed before and immediately after radiotherapy, at 3
      months and at 1 year. Perfusion, blood volume, mean transit time, delay,
      dispersion, interstitial volume, and extraction coefficient were calculated in
      prostate cancer and normal prostate for all four time points using a sequential 3
      compartment model. RESULTS: Prostate cancer and normal prostate tissue showed a
      statistically significant decrease in perfusion (p=0.006, p=0.001) and increase
      in extraction coefficient (p=0.004, p<0.001). For prostate cancer, there was also
      a decrease in vascular volume (p=0.034). The other parameters investigated showed
      no statistically significant changes. Statistically significant differences
      between prostate cancer and normal prostate tissue were only observed before
      radiotherapy, when prostate cancer showed significantly higher perfusion (1.84
      vs. 0.12 ml/cm(3)min, p=0.028) and a smaller extraction coefficient (0.42 vs.
      0.64, p=0.028). CONCLUSIONS: Two pharmacokinetic parameters, perfusion and
      extraction coefficient, appear to be suitable candidates for monitoring the
      response to percutaneous intensity-modulated radiotherapy of prostate cancer.

PMID- 19748144
TI  - Reply: An international review of patient safety measures in radiotherapy
      practice.

PMID- 19748145
TI  - Re the article: "Impact of the boost dose of 10Gy versus 26Gy in patients with
      early stage breast cancer after a microscopically incomplete lumpectomy: 10-year
      results of the randomised EORTC boost trial. On behalf of the EORTC Radiation
      Oncology and Breast Cancer Groups. Radiother Oncol 2009;90:80-5".

PMID- 19748146
TI  - Is a single arc sufficient in volumetric-modulated arc therapy (VMAT) for complex
      shaped target volumes?
AB  - PURPOSE: To compare step-and-shoot intensity-modulated radiotherapy (ss-IMRT)
      with volumetric-modulated arc therapy (VMAT) for complex-shaped target volumes
      with a simultaneous integrated boost (SIB). MATERIALS AND METHODS: This
      retrospective planning study was based on 20 patients composed of prostate cancer
      (n=5), postoperative (n=5) or primary (n=5) radiotherapy for pharyngeal cancer
      and for cancer of the paranasal sinuses (n=5); a SIB with two or three dose
      levels was planned in all patients. For each patient, one ss-IMRT plan with
      direct-machine-parameter optimization (DMPO) and VMAT plans with one to three
      arcs (SmartArc technique) were generated in the Pinnacle planning system.
      RESULTS: Single arc VMAT improved target coverage and dose homogeneity in
      radiotherapy for prostate cancer. Two and three VMAT arcs were required to
      achieve equivalent results compared to ss-IMRT in postoperative and primary
      radiotherapy for pharyngeal cancer, respectively. In radiotherapy for cancer of
      the paranasal sinuses, multiarc VMAT resulted in increased spread of low doses to
      the lenses and decreased target coverage in the region between the orbits.
      CONCLUSIONS: The complexity of the target volume determined whether single arc
      VMAT was equivalent to ss-IMRT. Multiple arc VMAT improved results compared to
      single arc VMAT at cost of increased delivery times, increased monitor unites and
      increased spread of low doses.

PMID- 19748147
TI  - Relations of lysophosphatidylcholine in low-density lipoprotein with serum
      lipoprotein-associated phospholipase A2, paraoxonase and homocysteine
      thiolactonase activities in patients with type 2 diabetes mellitus.
AB  - AIMS: We studied the relations of lysophosphatidylcholine (lyso-PC) in LDL with
      serum lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), paraoxonase and
      homocysteine thiolactonase (HTLase) activities in patients with type 2 diabetes
      mellitus. METHODS: Lyso-PC was measured by electrospray ionization-liquid
      chromatography/mass spectrometry. Paraoxonase and HTLase activities were measured
      with paraoxon and gamma-thiobutyrolactone as substrates, respectively. RESULTS:
      Serum HTLase and paraoxonase activities were significantly suppressed in diabetic
      patients (n=96) compared with control (n=25), whereas serum Lp-PLA(2) did not
      differ in control and diabetic patients. Lyso-PC contents in LDL correlated with
      serum Lp-PLA(2) activity positively and with serum HTLase activity negatively.
      Stepwise regression analysis revealed that serum Lp-PLA(2) and HTLase activities
      independently contributed to lyso-PC contents in LDL. In patients with diabetic
      nephropathy, lyso-PC contents in LDL were increased with reduced serum HTLase and
      paraoxonase activities compared with control, while serum Lp-PLA(2) activity did
      not differ. On the other hand, 3-month treatment with simvastatin reduced both
      lyso-PC contents in LDL and serum Lp-PLA(2) activity in hypercholesterolemic
      diabetic patients, while serum HTLase or paraoxonase activities did not change.
      CONCLUSIONS: Increased lyso-PC contents in LDL were associated with the
      suppressed HTLase activity, and serum Lp-PLA(2) and HTLase activities may be
      related to lyso-PC in type 2 diabetic patients.

PMID- 19748148
TI  - Gender differences in the socioeconomic gradient in self-reported diabetes: does
      health service access play a role?
AB  - AIMS: To investigate the hypothesis that gender difference in the socioeconomic
      gradient of self-reported diabetes might be partially determined by a detection
      bias: among low SEP men, but not women, a less frequent use of medical care would
      result in lower diabetes detection and awareness. METHODS: We conducted a cross
      sectional analysis of 2387 (57.1% women) Brazilian university non-faculty civil
      servants. We quantified the association between educational attainment (a marker
      of socioeconomic position) and self-reported diabetes through gender-specific
      logistic regression models adjusting for age. Health insurance coverage (a marker
      of potential health care access) and never having had serum cholesterol tested (a
      marker of actual care access) were analyzed to investigate the role of detection
      bias. RESULTS: Compared to participants with college education or higher, the
      adjusted odds ratio (OR) and 95% confidence interval for diabetes for those with
      less than high school was 2.5 (1.0-6.5) in men and 5.0 (2.1-11.7) in women. Only
      among men we observed an increment in this OR after an additional adjustment for
      markers of care access [men 3.5 (1.3-9.1); women 4.9 (1.9-12.1)]. CONCLUSIONS:
      Our findings suggest that health service access may explain some of the gender
      difference in the socioeconomic gradient of self-reported diabetes.

PMID- 19748149
TI  - Welfare state regimes and population health: integrating the East Asian welfare
      states.
AB  - Epidemiological studies have consistently shown that population health varies
      significantly by welfare state regime. However, these studies have focused
      exclusively on the welfare states of Europe, North America and Australasia. This
      focus ignores the existence of welfare states in other parts of the world,
      specifically in East Asia. This study therefore investigates whether the
      association between population health (Infant Mortality Rates and Life Expectancy
      at birth) and welfare state regimes is still valid when the welfare states of
      East Asia are added into the analysis. It also examines whether population health
      is worse in the East Asian welfare states. Infant Mortality Rates and Life
      Expectancy at birth as well as GDP per capita and social and health expenditures
      as a percentage of GDP were examined in 30 welfare states, categorised into six
      different regimes (Scandinavian, Anglo-Saxon, Bismarckian, Southern, Eastern
      European and East Asian). ANOVA analysis showed significant differences by
      welfare state regime in the magnitude of IMR, LE, SE, HE and GDP per capita.
      However, when controlling for GDP per capita in the ANCOVA analyses, only Life
      Expectancy (R(2)=0.58, adjusted R(2)=0.47, p<0.05) and Social Expenditure
      (R(2)=0.70, adjusted R(2)=0.61, p<0.05) differed significantly by welfare state
      regime. 47% of the variation in Life Expectancy was explained by welfare state
      regime type. Further, the East Asian welfare states did not have the worst health
      outcomes. The study concludes by highlighting the need to expand comparative
      health analysis both in terms of the range of countries examined and also in
      terms of incorporating other societal and public health factors-towards a 'public
      health regime' analysis.

PMID- 19748150
TI  - Metabolica: a statistical research tool for analyzing metabolic networks.
AB  - Steady state flux balance analysis (FBA) for cellular metabolism is used, e.g.,
      to seek information on the activity of the different pathways under equilibrium
      conditions, or as a basis for kinetic models. In metabolic models, the
      stoichiometry of the system, commonly completed with bounds on some of the
      variables, is used as the constraint in the search of a meaningful solution. As
      model complexity and number of constraints increase, deterministic approach to
      FBA is no longer viable: a multitude of very different solutions may exist, or
      the constraints may be in conflict, implying that no precise solution can be
      found. Moreover, the solution may become overly sensitive to parameter values
      defining the constraints. Bayesian FBA treats the unknowns as random variables
      and provides estimates of their probability density functions. This stochastic
      setting naturally represents the variability which can be expected to occur over
      a population and helps to circumvent the drawbacks of the classical approach, but
      its implementation can be quite tedious for users without background in
      statistical computations. This article presents a software package called
      Metabolica for performing Bayesian FBA for complex multi-compartment models and
      visualization of the results.

PMID- 19748151
TI  - Impacts of roads and linear clearings on tropical forests.
AB  - Linear infrastructure such as roads, highways, power lines and gas lines are
      omnipresent features of human activity and are rapidly expanding in the tropics.
      Tropical species are especially vulnerable to such infrastructure because they
      include many ecological specialists that avoid even narrow (<30-m wide) clearings
      and forest edges, as well as other species that are susceptible to road kill,
      predation or hunting by humans near roads. In addition, roads have a major role
      in opening up forested tropical regions to destructive colonization and
      exploitation. Here, we synthesize existing research on the impacts of roads and
      other linear clearings on tropical rainforests, and assert that such impacts are
      often qualitatively and quantitatively different in tropical forests than in
      other ecosystems. We also highlight practical measures to reduce the negative
      impacts of roads and other linear infrastructure on tropical species.

PMID- 19748152
TI  - Acid generation upon thermal concentration of natural water: the critical water
      content and the effects of ionic composition.
AB  - Thermal evaporation of a variety of simulated pore waters from the region of
      Yucca Mountain, Nevada, produced acidic liquids and gases during the final stages
      of evaporation. Several simulated pore waters were prepared and then thermally
      distilled in order to collect and analyze fractions of the evolved vapor. In some
      cases, distillates collected towards the end of the distillation were highly
      acidic; in other cases the pH of the distillate remained comparatively unchanged
      during the course of the distillation. The results suggest that the pH values of
      the later fractions are determined by the initial composition of the water. Acid
      production stems from the hydrolysis of magnesium ions, especially at near
      dryness. Near the end of the distillation, magnesium nitrate and magnesium
      chloride begin to lose water of hydration, greatly accelerating their thermal
      decomposition to form acid. Acid formation is promoted further when precipitated
      calcium carbonate is removed. Specifically, calcium chloride-rich pore waters
      containing moderate (10-20 ppm) levels of magnesium and nitrate and low levels of
      bicarbonate produced mixtures of nitric and hydrochloric acid, resulting in a
      precipitous drop in pH to values of 1 or lower after about 95% of the original
      volume was distilled. Waters with either low or moderate magnesium content
      coupled with high levels of bicarbonate produced slightly basic fractions (pH 7
      9). If calcium was present in excess of bicarbonate, waters containing moderate
      levels of magnesium produced acid even in the presence of bicarbonate, due to the
      precipitation of calcium carbonate. Other salts such as halite and anhydrite
      promote the segregation of acidic vapors from residual basic solids. The
      concomitant release of wet acid gas has implications for the integrity of the
      alloys under consideration for containers at the Yucca Mountain nuclear waste
      repository. Condensed acid gases at very low pH, especially mixtures of nitric
      and hydrochloric acid, are capable of corroding even alloys, such as nickel-based
      Alloy 22, which are considered to be corrosion-resistant under milder conditions.

PMID- 19748153
TI  - Commentary on "my embarrassment at not knowing Heinich". Untangling tensions: a
      consideration of epidermal-growth-control and developmental-hydraulic
      interpretations of tissue tension.

PMID- 19748154
TI  - My embarrassment at not knowing Heinich.

PMID- 19748155
TI  - Deep cutaneous fungal infections in immunocompromised children.
AB  - BACKGROUND: Life-threatening infections from ubiquitous fungi are becoming more
      prevalent in adults and children because of the increased use of
      immunosuppressive agents and broad-spectrum anti-infective drugs. Extremely low
      birth weight premature neonates and patients with a disrupted epidermal barrier
      are also at increased risk. Lethality is high, particularly with delayed
      diagnosis. As cutaneous lesions are often the first manifestation of such
      infections, early recognition of suspicious lesions is crucial to decrease
      associated morbidity and mortality. The clinical features of deep cutaneous
      fungal infection (DCFI) in immunocompromised children deserve special attention.
      OBJECTIVES: This study aimed to characterize our pediatric patients with DCFI,
      the causative fungi, and the associated risk factors. METHODS: A medical record
      review was conducted of pediatric patients with DCFI treated at out institution
      using data retrieved from the hospital's pathology and microbiology database
      (1980-2008). RESULTS: In all, 26 patients with DCFI were identified (9 girls and
      17 boys) ranging in age from 1 day to 18 years (mean age: 8 years), the majority
      of whom had a hematologic disorder. All patients were immunocompromised, 90% were
      receiving broad-spectrum antibiotics, and 50% had severe neutropenia (absolute
      neutrophilic count < or = 500 x 10(6)/L). Necrotic ulcers (42%) and papules (34%)
      represented the most frequent lesion morphology. Fungal species were identified
      by culture in 20 (87%) of 23 patients tested and were observed
      histopathologically in 20 of 23 patients tested. Aspergillus was identified in 12
      (44%) patients and Candida in 9 (33%). The other species included Fusarium (one),
      Exserohilum rostratum (one), Alternaria (one), Zygomycetes (two), and
      Blatomycetes (one). All but two patients received systemic antifungal therapy;
      wide surgical excision was performed in 13. Infection resolved in 20 (77%),
      whereas 6 (23%) died of disseminated infection. LIMITATIONS: This study was
      limited by the small number of cases and the retrospective nature of the
      collected data. DISCUSSION: DCFI should rank high in the differential diagnosis
      of any suspicious skin lesions in immunocompromised children. Early biopsies
      should be performed for histopathology and microbiological analysis, as lethality
      is high if appropriate treatment is delayed.

PMID- 19748156
TI  - Concerning the survival of saliva-borne oral bacteria on patient notes.

PMID- 19748157
TI  - Stockpile of personal protective equipment in hospital settings: preparedness for
      influenza pandemics.
AB  - BACKGROUND: Personal protective equipment (PPE) is known to be a crucial means of
      preventing influenza pandemics; however, the amount of PPE that should be stored
      in hospital settings has been unclear. OBJECTIVES: The purpose of this paper is
      to propose a PPE calculation system to help hospitals to decide their PPE
      stockpile. METHODS: We searched influenza guidelines from a number of countries
      and research papers on protective devices and infectious diseases. The PPE
      calculation system included factors such as the influenza pandemic period, risk
      classification by health care workers (HCW) type, and the type and number of PPE
      for a HCW per day. RESULTS: We concluded that 4 sets of PPE (N95 respirators,
      double gloves, gowns, and goggles) per day should be prepared for HCWs in a high
      risk group. Similarly, 2 sets of appropriate PPE, depending on the risk level,
      are required for medium- and low-risk groups. In addition, 2 surgical masks are
      required for every worker and inpatient and 1 for each outpatient. The PPE
      stockpile should be prepared to cover at least an 8-week pandemic. CONCLUSION:
      Purchasing a PPE stockpile requires a sizable budget. The PPE calculation system
      in this paper will hopefully support hospitals in deciding their PPE stockpile.

PMID- 19748158
TI  - A comparison of the hand hygiene knowledge, beliefs, and practices of Greek
      nursing and medical students.

PMID- 19748159
TI  - Progression from MCI to AD: predictive value of CSF Abeta42 is modified by APOE
      genotype.
AB  - OBJECTIVE: To study CSF biomarkers amyloid-beta 1-42 (Abeta42) and total tau
      (tau) in relation to APOE genotype in their ability to predict progression from
      mild cognitive impairment (MCI) to Alzheimer's disease (AD). METHODS: In 100 MCI
      patients CSF Abeta42, tau and APOE genotype were determined. At follow-up of 18
      (13-24) months 58 patients remained non-progressive and 42 progressed to AD.
      RESULTS: Cox proportional hazards models showed an interaction between Abeta42
      and APOE genotype (p<0.05). Stratification for APOE revealed HR (95% CI) for
      abnormal Abeta42 of 8.2 (2.1-31.9) for epsilon4 non-carriers, 3.9 (0.8-18.5) for
      heterozygotes and 0.3 (0.0-1.7) for homozygotes. Inversely, stratification for
      Abeta42 revealed that in patients with normal levels of Abeta42, epsilon4
      homozygotes had a strongly increased risk of progression to AD with HR (95% CI)
      20.8 (2.4-182.8). Tau and APOE independently predicted progression to AD.
      CONCLUSIONS: Abeta42 was a stronger predictor of progression to AD in APOE
      epsilon4 non-carriers than in carriers. Furthermore, the risk of progression for
      epsilon4 homozygotes was very high, also in patients with normal levels of
      Abeta42.

PMID- 19748160
TI  - [Trends in socioeconomic inequalities in mortality over a twenty-two-year period
      in the city of Barcelona (Spain)].
AB  - OBJECTIVE: To analyze the trend in socioeconomic inequalities in all-cause
      mortality in Barcelona from 1983 to 2004. METHODS: We performed an ecological
      study of trends over 4 cross-sections (1983-1988, 1989-1994, 1995-1999 and 2000
      2004), with the basic health area (BHA) as the unit of analysis. The study
      population consisted of men and women aged 20 years or more living in Barcelona.
      The information sources were the mortality registry, the municipal census and the
      census of inhabitants and dwellings. The age- and sex-specific mortality rate
      (ASMR) for all causes was used as the dependent variable. As the independent
      variable, a composite index of socioeconomic deprivation of the BHA was
      calculated; BHAs were grouped in quartiles according to the values on the index.
      Poisson models were adjusted to estimate the relative risk of mortality from all
      causes in the 4 groups of BHA, stratified by age groups and sex. RESULTS: In all
      the study periods, inequalities in mortality were found, depending on the BHA of
      residence, both for men and for women: the ASMR of the most deprived BHAs were
      greater than those of less deprived BHA, and were greater among men than among
      women. Likewise, relative risks in the youngest age groups were higher than in
      the oldest age groups. However, from the second to fourth study periods,
      inequalities decreased in absolute and relative terms, especially among men.
      CONCLUSIONS: Inequalities in mortality persist in BHA in Barcelona but have
      decreased over the last 2 decades. Public policies should take this information
      into account when tackling inequalities among BHA.

PMID- 19748161
TI  - [Impact of the distinct diagnostic criteria used in population-based studies on
      estimation of the prevalence of knee osteoarthritis].
AB  - OBJECTIVE: To assess the impact of the distinct diagnostic criteria used in
      population-based studies on estimation of the prevalence of knee osteoarthritis.
      METHODS: We performed a search for population-based studies of the prevalence of
      knee osteoarthritis carried out in the general noninstitutionalized population in
      Europe or the USA. RESULTS: Eight articles were selected, six from Europe and two
      from the USA. Depending on the study, definition of knee osteoarthritis was based
      on symptomatic criteria (pain), radiological criteria (the Kellgren and Lawrence
      scale) or a combination of both symptomatic and radiological criteria. Prevalence
      estimates ranged from 2.0 to 42.4% with symptomatic criteria, from 16.3 to 33.0%
      with radiological criteria, and from 1.5 to 15.9% when both criteria were
      combined. The prevalence was higher for women and increased with age, with the
      exception of some prevalences estimated through symptoms, which decreased in ages
      older than 80 years. CONCLUSIONS: There is a lack of consensus on the criteria
      used to diagnose knee osteoarthritis in population-based studies of prevalence.
      Consequently, prevalence estimates vary widely, depending on the diagnostic
      criteria used, and not only by age and sex. The prevalence was higher when
      radiological evidence alone was used, followed by symptomatic criteria and by
      combinations of both.

PMID- 19748162
TI  - [Preventive intervention in venues for interaction used by men who have sex with
      men].
AB  - An intervention in venues for interaction used by men who have sex with men in
      Valencia (Spain) was performed to prevent human immunodeficiency virus (HIV)
      infection or avoid delay in diagnosis and to facilitate contact with the health
      circuit. Information was provided on prevention and a rapid test for HIV and
      syphilis was performed. We contacted 500 men and the intervention was performed
      in 171; 37% of the subjects in saunas and one in four of those in prostitution
      apartments had never been tested. The prevalence of HIV was 1.6% (n=2) in the
      saunas, and 11% (n=5) in the apartments (n=5). For syphilis, these percentages
      were 5% and 2.3% respectively. The intervention revealed the existence of highly
      exposed population groups with low compliance and facilitated access to the
      health system in these groups.

PMID- 19748163
TI  - [Extramedullary blastic transformation revealed by a prolonged fever during the
      course of a 5q- syndrome].
AB  - INTRODUCTION: Fever during a myelodysplastic syndrome can be due to infectious
      complications, systemic disease or acute transformation with clonal evolution.
      CASE REPORT: A 51-year-old woman, with a 5q- syndrome and neutropenia, presented
      with a several week fever duration. Infectious work-up was negative and therapy
      with antibiotics had no influence on the clinical course. Neither bone marrow nor
      blood blasts were detected, but liver biopsy demonstrated significant blast
      infiltration compatible with the diagnosis of acute myeloid leukaemia (AML).
      CONCLUSION: The absence of blasts in blood or bone marrow does not exclude the
      malignant transformation of a myelodysplastic syndrome to AML. Tissue biopsy may
      be necessary to confirm the leukaemic progression.

PMID- 19748164
TI  - Inhibition of JNK along with activation of ERK1/2 MAPK pathways improve
      steatohepatitis among the rats.
AB  - BACKGROUND & AIMS: Oxidative stress-induced hepatocyte apoptosis is implicated in
      the onset of non-alcoholic steatohepatitis (NASH). Regarding the pronounced roles
      of mitogen activated protein kinases (MAPKs) in oxidative stress-induced cellular
      damages and the development of NASH, we evaluated the effect of Teucrium polium
      ethyl acetate (EtoAc) extract on rats with NASH and on the modulation of MAPKs
      activities. METHODS: To induce NASH, a methionine choline deficient diet (MCD)
      was given to N-Mary rats. These animals were then compared to the control group
      receiving normal diet and/or MCD diet plus EtoAc extract (0.5g/kg/day). After 8
      weeks, liver histopathology, malondialdehyde (MDA) and immunoblot analyses of
      caspase-3 cleavage, ERK/pERK and JNK/pJNK were examined. RESULTS: Simultaneous
      treatments with MCD diet and the EtoAc extract resulted in pronounced
      improvements in liver steatosis, ballooning degeneration and inflammation.
      Elevated MDA and caspase-3 levels among MCD-fed rats were also markedly
      decreased. In addition, the EtoAc extract treatments caused significant reduction
      in the phosphorylated form of JNK along with an increase in the phosphorylated
      level of ERK1/2. CONCLUSION: These results indicate that the anti-apoptotic
      effect of T. polium extract is mediated through inhibition of ROS generation.
      Moreover, the inhibitory effect of T. polium on the development and progression
      of NASH is apparently governed by the attenuation of JNK activation and
      augmentation of ERK1/2 activity through phosphorylation.

PMID- 19748165
TI  - The relationship between the insulin-like growth factor-1 axis, weight loss, an
      inflammation-based score and survival in patients with inoperable non-small cell
      lung cancer.
AB  - BACKGROUND & AIMS: The involvement of a systemic inflammatory response, as
      evidenced by the Glasgow Prognostic Score (GPS), is associated with weight loss
      and poor outcome in patients with non-small cell lung cancer. There is good
      evidence that nutritional and functional decline in patients with advanced
      malignant disease is associated with catabolic changes in metabolism. However,
      defects in anabolism may also contribute towards nutritional decline in patients
      with cancer. The aim of the present study was to examine the relationship between
      IGF-1 and IGFBP-3, performance status, mGPS and survival in patients with
      inoperable NSCLC. METHODS: 56 patients with inoperable NSCLC were studied. The
      plasma concentrations of IGF-1, IGFBP-3 and leptin were measured using ELISA and
      RIA. RESULTS: The patients were predominantly male (61%), over 60 years old
      (80%), with advanced (stage III or IV) disease (98%), with a BMI> or =20 (84%),
      an ECOG-ps of 0 or 1 (79%), a haemoglobin (59%) and white cell count (79%) in the
      reference range. On follow-up 43 patients died of their cancer. On univariate
      analysis, BMI (p<0.05), Stage (p<0.05), ECOG-ps (p<0.05), haemoglobin (p<0.05),
      white cell count (p<0.05) and mGPS (p<0.05) were associated with cancer specific
      survival. There was no association between age, sex, treatment, IGF-1, IGFBP-3,
      IGF-1:IGFBP-3 ratio, or leptin and cancer specific survival. With an increasing
      mGPS concentrations of haemoglobin (p<0.005) and IGFBP-3 (p<0.05) decreased. mGPS
      was not associated with either IGF-1(p>0.20), or leptin (p>0.20). CONCLUSIONS: In
      summary, the results of this study suggest that anabolism (IGF-1 axis) does not
      play a significant role in the relationship between nutritional and functional
      decline, systemic inflammation and poor survival in patients with inoperable
      NSCLC.

PMID- 19748167
TI  - A critical reflection on the role of social democracy in reducing socioeconomic
      inequalities in health: a commentary on Sekine, Chandola, Martikainen, Marmot and
      Kagamimori.

PMID- 19748166
TI  - Addressing tobacco use disorder in smokers in early remission from alcohol
      dependence: the case for integrating smoking cessation services in substance use
      disorder treatment programs.
AB  - Despite the declining overall rate of cigarette smoking in the general population
      in the United States, the prevalence of smoking is estimated to be as high as 80%
      among treatment-seeking alcoholics. The serious adverse health effects of tobacco
      and heavy alcohol use are synergistic and recent evidence suggests that smoking
      slows the process of cognitive recovery following alcohol abstinence. In
      addition, substantial evidence shows that treatment for tobacco dependence does
      not jeopardize alcohol abstinence. In this paper, we focus on the impact and
      treatment implications of tobacco dependence among treatment-seeking alcoholics
      through a review of five areas of research. We begin with brief reviews of two
      areas of research: studies investigating the genetic and neurobiological
      vulnerability of comorbid tobacco and alcohol dependence and studies
      investigating the consequences of comorbid dependence on neurobiological and
      cognitive functioning. We then review literature on the effects of smoking
      cessation on drinking urges and alcohol use and the effectiveness of smoking
      cessation interventions with alcoholic smokers. Finally, we offer recommendations
      for research with an emphasis on clinical research for enhancing smoking
      cessation outcomes in this population.

PMID- 19748168
TI  - Inequality in individual mortality and economic conditions earlier in life.
AB  - We analyze the effect of being born in a recession on the mortality rate later in
      life in conjunction with social class. We use individual data records from Dutch
      registers of birth, marriage, and death certificates, covering the period 1815
      2000, and we merge these with historical data on macro-economic outcomes and
      health indicators. We estimate duration models and inequality measures. The
      results indicate that being born in a recession increases the mortality rate
      later in life for most of the population. Lower social classes suffer
      disproportionally from being born in recessions. This exacerbates mortality
      inequality. Upward mobility does not vary much with the business cycle at birth.

PMID- 19748169
TI  - Anger, PTSD, and the nuclear family: a study of Cambodian refugees.
AB  - This study profiles the family-directed anger of traumatized Cambodian refugees,
      all survivors of the Pol Pot genocide (1975-1979), who were patients at a
      psychiatric clinic in Lowell, MA, USA. We focus on the nuclear family (NF) unit,
      the NF unit defined as the patient's "significant other" (i.e. spouse or
      boyfriend/girlfriend) and children. Survey data were collected from a convenience
      sample of 143 Cambodian refugee patients from October 2006 to August 2007. The
      study revealed that 48% (68/143) of the patients had anger directed toward a NF
      member in the last month, with anger directed toward children being particularly
      common (64 of the 143 patients, or 49% [64/131] of the patients with children).
      NF-type anger was severe, for example, almost always resulting in somatic arousal
      (e.g., causing palpitations in 91% [62/68] of the anger episodes) and often in
      trauma recall and fears of bodily dysfunction. Responses to open-ended questions
      revealed the causes of anger toward a significant other and children, the content
      of anger-associated trauma recall, and what patients did to gain relief from
      anger. A type of cultural gap, namely, a linguistic gap (i.e., the parent's lack
      of English language skills and the child's lack of Khmer language skills),
      seemingly played a role in generating conflict and anger. NF-type anger was
      associated with PTSD presence. The effect of anger on PTSD severity resulted in
      part from anger-associated trauma recall and fears of bodily dysfunction, with
      54% of the variance in PTSD severity explained by that regression model. The
      study: 1) suggests that among traumatized refugees, family-related anger is a
      major clinical concern; 2) illustrates how family-related anger may be profiled
      and investigated in trauma-exposed populations; and 3) gives insights into how
      family-related anger is generated in such populations.

PMID- 19748170
TI  - Social capital, gender and self-rated health. Evidence from the Moscow Health
      Survey 2004.
AB  - The state of public health in Russia is undoubtedly poor compared with other
      European countries. The health crisis that has characterised the transition
      period has been attributed to a number of factors, with an increasing interest
      being focused on the impact of social capital - or the lack of it. However, there
      have been relatively few studies of the relation between social capital and
      health in Russia, and especially in Moscow. The aim of this study is to examine
      the relationship between social capital and self-rated health in Greater Moscow.
      The study draws on data from the Moscow Health Survey 2004, where 1190 Muscovites
      were interviewed. Our results indicate that among women, there is no relationship
      between any form of social capital and self-rated health. However, an association
      was detected between social capital outside the family and men's self-rated
      health. Men who rarely or never visit friends and acquaintances are significantly
      more likely to report less than good health than those who visit more often.
      Likewise, men who are not members of any voluntary associations have
      significantly higher odds of reporting poorer health than those who are, while
      social capital in the family does not seem to be of importance at all. We suggest
      that these findings might be due to the different gender roles in Russia, and the
      different socializing patterns and values embedded in them. In addition,
      different forms of social capital provide access to different forms of resources,
      influence, and support. They also imply different obligations. These differences
      are highly relevant for health outcomes, both in Moscow and elsewhere.

PMID- 19748172
TI  - In search of the perfect crystal ball for Ta urothelial cancer.

PMID- 19748174
TI  - The AdVance transobturator male sling for postprostatectomy incontinence:
      clinical results of a prospective evaluation after a minimum follow-up of 6
      months.
AB  - BACKGROUND: Transobturator male slings have been proposed to manage stress
      urinary incontinence (SUI) after prostatic surgery, but data are still lacking.
      OBJECTIVE: To determine the safety and prospectively evaluate the clinical
      outcome after management of SUI after prostatic surgery by placement of a
      transobturator male sling. DESIGN, SETTING, AND PARTICIPANTS: We conducted a
      prospective evaluation on 102 patients treated in a single center between 2007
      and 2009 for mild to moderate SUI following prostatic surgery. INTERVENTIONS:
      Placement of a suburethral transobturator sling and clinical follow-up.
      MEASUREMENTS: Patients were evaluated by medical history, preoperative
      urodynamics, maximum flow rate measurement, 24-h pad test, and daily pad use.
      During follow-up, data on patients' pad use, complications, and answers to the
      Patient Global Impression of Improvement (PGI-I) questionnaire were collected.
      Cure was defined as no pad usage or one pad for security reasons and improvement
      as reduction of pads>=50%. Median follow-up was 13 mo (range: 6-26). RESULTS AND
      LIMITATIONS: Most patients (95%) presented post-radical prostatectomy
      incontinence (PRPI). Hospital stay was 2 d in 97 cases, and all patients were
      catheterized for 24h except two (48 h). Of 102 patients, 64 were cured, 18 were
      improved, and 20 were not improved. According to the PGI-I questionnaire, 85%,
      11%, and 4% of patients described a respectively better, unchanged, and worse
      urinary tract condition, respectively. Previous radiation was associated with
      higher rate of failure (p=0.039). Neither severe complication nor postoperative
      urinary obstruction was noted during follow-up. CONCLUSIONS: Placement of a
      transobturator sling is a safe and effective procedure, giving durable results
      after >1 yr of follow-up. Further evaluation and high-quality controlled,
      randomized studies are needed to assess long-term efficacy and precise
      indications of this procedure for post-prostatic-surgery SUI management.

PMID- 19748175
TI  - A subpopulation of CD133(+) cancer stem-like cells characterized in human oral
      squamous cell carcinoma confer resistance to chemotherapy.
AB  - The potential role of cancer stem-like cells (CSCs) in chemoresistance of human
      oral squamous cell carcinoma (OSCC) was examined. A small subpopulation (1-2%) of
      CD133(+) CSCs was identified in OSCC cell lines and tissues. These CD133(+) CSCs
      possess higher clonogenicity, invasiveness, and increased in vivo tumorigenicity
      as compared to CD133(-) counterparts. Meanwhile, CD133(+) CSCs were substantially
      resistant to standard chemotherapy, wherein both in vitro and in vivo treatment
      with paclitaxel resulted in a marked enrichment for CD133(+) CSCs. Our data
      suggest that CD133(+) cells represent a small subpopulation of CSCs that may
      contribute to chemoresistance in human OSCC.

PMID- 19748176
TI  - An eco-friendly process: predictive modelling of copper adsorption from aqueous
      solution on Spirulina platensis.
AB  - The adsorption of copper ions on Spirulina platensis was studied as a function of
      contact time, initial metal ion concentration, and initial pH regimes.
      Characterization of this adsorbent was confirmed by FTIR spectrum. Modified
      Gompertz and Logistic models have not been previously applied for the adsorption
      of copper. Logistic was the best model to describe experimental kinetic data.
      This adsorption could be explained by the intra-particle diffusion, which was
      composed of more than one sorption processes. Langmuir, Freundlich, and Redlich
      Peterson were fitted to equilibrium data models. According to values of error
      functions and correlation coefficient, the Langmuir and Redlich-Peterson models
      were more appropriate to describe the adsorption of copper ions on S. platensis.
      The monolayer maximum adsorption capacity of copper ions was determined as 67.93
      mg g(-1). Results indicated that this adsorbent had a great potential for
      removing of copper as an eco-friendly process.

PMID- 19748177
TI  - Phosphate filtering characteristics of a hybridized porous Al alloy prepared by
      surface modification.
AB  - In this study, a porous Al alloy filter was designed for water purification
      systems. The combination of higher permeability for fluid flow and excellent
      filtering characteristics for removing pollutants is required for water
      purification. The filter's macropore structure was controlled by a powder
      metallurgical process using granulated powders for high permeability and its
      micropore structure was generated by alkali surface modification on the
      macroporous sintered body for enhanced filtration efficiency. After surface
      modification, the specific surface area was increased by 10 times over the as
      sintered specimen. Phosphate filtering characteristic was noticeably improved by
      a ligand exchange between phosphate and aluminum hydroxide formed by alkali
      surface modification.

PMID- 19748178
TI  - Removal of hexavalent chromium [Cr(VI)] from aqueous solutions by the diatomite
      supported/unsupported magnetite nanoparticles.
AB  - Diatomite-supported/unsupported magnetite nanoparticles were prepared by co
      precipitation and hydrosol methods, and characterized by X-ray diffraction,
      nitrogen adsorption, elemental analysis, differential scanning calorimetry,
      transmission electron microscopy and X-ray photoelectron spectroscopy. The
      average sizes of the unsupported and supported magnetite nanoparticles are around
      25 and 15 nm, respectively. The supported magnetite nanoparticles exist on the
      surface or inside the pores of diatom shells, with better dispersing and less
      coaggregation than the unsupported ones. The uptake of hexavalent chromium
      [Cr(VI)] on the synthesized magnetite nanoparticles was mainly governed by a
      physico-chemical process, which included an electrostatic attraction followed by
      a redox process in which Cr(VI) was reduced into trivalent chromium [Cr(III)].
      The adsorption of Cr(VI) was highly pH-dependent and the kinetics of the
      adsorption followed a pseudo-second-order model. The adsorption data of diatomite
      supported/unsupported magnetite fit well with the Langmuir isotherm equation. The
      supported magnetite showed a better adsorption capacity per unit mass of
      magnetite than unsupported magnetite, and was more thermally stable than their
      unsupported counterparts. These results indicate that the diatomite
      supported/unsupported magnetite nanoparticles are readily prepared, enabling
      promising applications for the removal of Cr(VI) from aqueous solution.

PMID- 19748179
TI  - Studies on destruction of silicon tetrachloride using microwave plasma jet.
AB  - A new method for destroying silicon tetrachloride has been proposed, which is
      based on a microwave plasma jet that operates at atmospheric pressure using
      hydrogen as work gas. The influence of input power (P) and silicon tetrachloride
      concentration (phi) on the percent destruction and removal of SiCl(4) was
      investigated. And the reclaimed solid byproducts were characterized by SEM, EDX
      and XRD. Species in the plasma, which were identified by atomic emission
      spectroscopy were found to include no halogen. Results indicate that the
      destruction efficiency of silicon tetrachloride can reach 96% when P=800 W and
      phi=1.0%, and the main solid byproduct was Si. The silicon deposited on the
      molybdenum substrate of the plasma reactor was yellow and typical nano-sized
      particles with grain size of 54 nm.

PMID- 19748180
TI  - Enhanced phytoremediation potential of polychlorinated biphenyl contaminated soil
      from e-waste recycling area in the presence of randomly methylated-beta
      cyclodextrins.
AB  - The crude recycling of electronic and electric waste (e-waste) is now creating
      soil pollution problems with organic compounds such as polychlorinated biphenyls
      (PCBs). The present study aimed to compare the phytoremediation potential of four
      plant species (rice, alfalfa, ryegrass and tall fescue) for PCBs contaminated
      soil from Taizhou city, one of the largest e-waste recycling centers in China. In
      addition, the enhanced effects of randomly methylated-beta-cyclodextrins (RAMEB)
      on PCBs phytoremediation potential were evaluated. Higher PCBs removal
      percentages of 25.6-28.5% in rhizosphere soil were observed after 120 days,
      compared with those of the non-rhizosphere (10.4-16.9%) and unplanted controls
      (7.3%). The average PCBs removal percentages of four plant species increased from
      26.9% to 37.1% in the rhizosphere soil with addition of RAMEB. Meanwhile,
      relatively high microbial counts and dehydrogenase activity were detected in
      planted soils and a stimulatory effect by RAMEB addition was found. The present
      study indicated that all the plant candidates were feasible for phytoremediation
      of PCBs contaminated soil from the e-waste recycling area, and tall fescue with
      RAMEB amendment seemed as a promising remediation strategy. High PCBs removal
      percentage was due to the increased PCBs bioavailability as well as
      biostimulation of microbial communities after plantation and RAMEB addition.

PMID- 19748181
TI  - Short-time effect of heavy metals upon microbial community activity.
AB  - Microcalorimetry was applied to assess and compare the toxic effect of heavy
      metals, such as As, Cu, Cd, Cr, Co, Pb and Zn, on the soil microbial activities
      and community. About 1.0 g soil spiked 5.0mg glucose and 5.0mg ammonium sulfate,
      the microbial activities were recorded as power-time curves, and their indices,
      microbial growth rate constant k, total heat evolution Q(T), metabolic enthalpy
      Delta H(met) and mass specific heat rate J(Q/S), were calculated. Comparing these
      thermodynamic parameters associated with growth yield, a general order of
      toxicity to the soil was found to be Cr>Pb>As>Co>Zn>Cd>Cu. When soil was exposed
      to heavy metals, the amount of bacteria and fungi decreased with the incubation
      time, and the bacterial number diminished sharply. It illustrates that fungi are
      more tolerant, and bacteria-fungi ratio would be altered under metal stress. To
      determine the status of the glucose consumed, a glucose biosensor with eggshell
      membrane was used to measure the remaining glucose in soil sample. Results showed
      that the time at which glucose was consumed completely was agreed with the
      microcalorimetric time to a large extent, and depended on the toxicity of heavy
      metals as well.

PMID- 19748182
TI  - Typical pollutants in bottom ashes from a typical medical waste incinerator.
AB  - Incineration of medical waste (MW) is an important alternative way for disposal
      of this type of hazardous waste, especially in China because of the outbreak of
      severe acute respiratory syndromes (SARs) in 2003. Thus, far, fly ash has
      received much attention but less attention has been paid to bottom ash. In this
      study, bottom ash samples were collected from a typical MW incinerator, and
      typical pollutants including heavy metals and polycyclic aromatic hydrocarbons
      (PAHs) in the ash were examined. X-ray fluorescence spectroscopy results
      indicated that CaO, SiO(2) and Al(2)O(3) were the main components of the bottom
      ash. Inductively coupled plasma-optical emission spectroscopy showed that the ash
      contained large amounts of heavy metals, including Zn, Ti, Ba, Cu, Pb, Mn, Cr, Ni
      and Sn. Most of the heavy metals (e.g., Ba, Cr, Ni, and Sn) presented in the
      residual fraction; whereas Mn, Pb and Zn presented in Fe-Mn oxides fraction, and
      Cu in organic-matter fraction. Toxicity characteristic leaching procedure tests
      indicated that the leached amounts of heavy metals were well below the limits.
      The sum of 16 US EPA priority PAHs (Sigma PAHs) varied from 10.30 to 38.14 mg kg(
      1), and the total amounts of carcinogenic PAHs ranged between 4.09 and 16.95 mg
      kg(-1), exceeding the limits regulated by several countries. This research
      provides basic information for the evaluation of the environmental risk of MW
      incinerator bottom ash.

PMID- 19748183
TI  - Treatment of rinse water from zinc phosphate coating by batch and continuous
      electrocoagulation processes.
AB  - Treatment of spent final rinse water of zinc phosphating from an automotive
      assembly plant was investigated in an electrochemical cell equipped with aluminum
      or iron plate electrodes in a batch mode by electrocoagulation (EC). Effects of
      the process variables such as pH, current density, electrode material and
      operating time were explored with respect to phosphate and zinc removal
      efficiencies, electrical energy and electrode consumptions. The optimum operating
      conditions for removal of phosphate and zinc were current density of 60.0 A/m(2),
      pH 5.0 and operating time of 25.0 min with Al electrode and current density of
      60.0 A/m(2), pH 3.0 and operating time of 15.0 min with Fe electrode,
      respectively. The highest phosphate and zinc removal efficiencies at optimum
      conditions were 97.7% and 97.8% for Fe electrode, and 99.8% and 96.7% for Al
      electrode. The electrode consumptions increased from 0.01 to 0.35 kg
      electrode/m(3) for Al electrode and from 0.20 to 0.62 kg electrode/m(3) for Fe
      electrode with increasing current density from 10.0 to 100.0 A/m(2). The energy
      consumptions were 0.18-11.29 kWh/m(3) for Al electrode and 0.24-8.47 kWh/m(3) for
      Fe electrode in the same current density range. Removal efficiencies of phosphate
      and zinc were found to decrease when flow rate was increased from 50 to 400
      mL/min in continuous mode of operation. The morphology and elements present in
      the sludge was also characterized by using SEM and EDX.

PMID- 19748184
TI  - Perisurgical amitriptyline produces a preventive effect on afferent
      hypersensitivity following spared nerve injury.
AB  - Following surgery, nerve injury can lead to persistent neuropathic pain. Pre
      emptive and preventive analgesic treatments in the perioperative period aim to
      minimize nerve injury-induced pain. Here we demonstrate that a perioperative
      regimen of amitriptyline (10 mg/kg i.p. 30 min before and immediately after
      surgery, followed by oral amitriptyline 15-18 mg/kg/day in the drinking water for
      7 days post-surgery) prevents hypersensitivity to a chemogenic stimulus
      (alphabeta-MeATP, a ligand for P2X3 receptors, together with noradrenaline or NA)
      in the spared nerve injury (SNI) model in rats. It also prevents hyposensitivity
      to capsaicin and NA. However, amitriptyline treatment had no effect on the
      development of mechanical allodynia. We investigated the role of NA mechanisms in
      the action of amitriptyline by using the neurotoxin 6-hydroxydopamine (6-OHDA)
      and by examining desipramine. Intrathecal treatment with 6-OHDA on the day of
      surgery reversed the preventive effect of amitriptyline on hypersensitivity to
      alphabeta-MeATP/NA, and desipramine exhibited a similar effect to amitriptyline.
      We also examined the effect of antibodies to the nerve growth factors glial
      derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF),
      given intrathecally three times (days 0, 3 and 7) on the action of amitriptyline
      and observed that the interruption of GDNF and BDNF signaling impaired the
      prevention of hypersensitivity to alphabeta-MeATP/NA. This study indicates that
      tricyclic antidepressants given in the perioperative period may be useful in
      preventing nerve injury-induced sensory changes that contribute to the
      development of chronic post-surgical neuropathic pain.

PMID- 19748185
TI  - Clinical effectiveness: an approach to clinical trial design more relevant to
      clinical practice, acknowledging the importance of individual differences.

PMID- 19748186
TI  - Lapatinib: a competitor or companion to trastuzumab?
AB  - Trastuzumab (Herceptin), a monoclonal antibody against HER2 has established
      itself as the treatment paradigm of HER2-overexpressing breast cancer. Its
      success, however, has been tempered by its sequelae. In particular, most tumours
      become resistant to trastuzumab through a variety of mechanisms. Furthermore,
      there is both an increased incidence of cardiac dysfunction and a worrying
      pattern of CNS metastasis associated with trastuzumab. To manage these concerns,
      many new treatments targeting HER2 have been developed. Of these emerging
      therapies, the dual tyrosine kinase receptor inhibitor against EGFR and HER2,
      lapatinib (Tyverb/Tykerb) has shown the most promise to date. Encouraging early
      results in vitro have now been reproduced in phase II/III clinical trials, both
      as lapatinib monotherapy and synergistically with other established therapeutic
      regimes, including trastuzumab itself. Trial results suggest it may be of
      considerable benefit to patients with trastuzumab-resistant tumours and may play
      a role in the reduction of CNS relapses. In addition, lapatinib is well-tolerated
      and unlike trastuzumab, minimal cardiac dysfunction has been documented. A number
      of trials are underway to assess whether lapatinib will oust trastuzumab from its
      pole position in the management of HER2-positive breast cancer or whether their
      combination will prove to be superior to either therapy alone.

PMID- 19748187
TI  - Historical evidence that electrification caused the 20th century epidemic of
      "diseases of civilization".
AB  - The slow spread of residential electrification in the US in the first half of the
      20th century from urban to rural areas resulted by 1940 in two large populations;
      urban populations, with nearly complete electrification and rural populations
      exposed to varying levels of electrification depending on the progress of
      electrification in their state. It took until 1956 for US farms to reach urban
      and rural non-farm electrification levels. Both populations were covered by the
      US vital registration system. US vital statistics tabulations and census records
      for 1920-1960, and historical US vital statistics documents were examined.
      Residential electrification data was available in the US census of population for
      1930, 1940 and 1950. Crude urban and rural death rates were calculated, and death
      rates by state were correlated with electrification rates by state for urban and
      rural areas for 1940 white resident deaths. Urban death rates were much higher
      than rural rates for cardiovascular diseases, malignant diseases, diabetes and
      suicide in 1940. Rural death rates were significantly correlated with level of
      residential electric service by state for most causes examined. I hypothesize
      that the 20th century epidemic of the so called diseases of civilization
      including cardiovascular disease, cancer and diabetes and suicide was caused by
      electrification not by lifestyle. A large proportion of these diseases may
      therefore be preventable.

PMID- 19748188
TI  - The Double Strike Hypothesis of the vitiligo pathomechanism: new approaches to
      vitiligo and melanoma.
AB  - Based on current research, we present a consolidated set of theses which explain
      the pathomechanisms of vitiligo- and melanoma-associated hypopigmentation. The
      main thesis is the Double Strike Hypothesis, i.e. vitiligo is caused by at least
      two different major pathomechanisms: an antibody-based pathomechanism and a T
      cell-based pathomechanism. The antibody-based pathomechanism is dominant in
      diffuse vitiligo, while the T-cell based pathomechanism is dominant in localised
      vitiligo. Based on this main thesis we derive new therapeutical approaches to
      vitiligo and melanoma by using the different pathomechanisms. Finally we explain
      why melanoma-associated hypopigmentation as a natural immunotherapy is still in
      statu nascendi.

PMID- 19748189
TI  - Similarities in features of autism and asthma and a possible link to
      acetaminophen use.
AB  - Autism and autism spectrum disorders are enigmatic conditions that have their
      origins in the interaction of genes and environmental factors. In this
      hypothesis, genes statistically associated with autism are emphasized to be
      important in inflammation and in innate immune pathways, including pathways for
      susceptibility to asthma. The role of acetaminophen (paracetamol) in an increased
      risk for asthma is described and a possible similar link to an increased risk for
      autism is suggested.

PMID- 19748190
TI  - Prolactin fragmentation by trophoblastic matrix metalloproteinases as a possible
      contributor to peripartum cardiomyopathy and pre-eclampsia.
AB  - Although peripartum cardiomyopathy (PPCM) is a rare disease, it has very serious
      consequences for both mother and child. No single cause has been held responsible
      for the pathogenesis. Recent studies have indicated that increased proteolytic
      cathepsin D activity in cardiomyocytes results in16kDa prolactin fragments with
      anti-angiogenic and apoptotic properties, which may contribute to the development
      of PPCM. In support of these findings, lowering full-length prolactin production
      by bromocriptine therapy has been reported to prevent impairment of cardiac
      function. PPCM is associated with an increased co-existence of pre-eclampsia,
      however, a causal relationship has been disputed. We hypothesize that the
      pathophysiology of PPCM and pre-eclampsia share the same molecular pathway:
      increased activity of trophoblastic matrix metalloproteinases at the feto
      maternal interface may aggravate proteolysis of full-length prolactin, and
      subsequently the formed 16kDa prolactin fragments may contribute to deterioration
      of PPCM and pre-eclampsia. Therefore, we argue that it may be worthwhile to
      explore wether prolactin inhibition is not only beneficial for PPCM patients, but
      also for the much more prevalent pre-eclamptic women.

PMID- 19748191
TI  - Regulation of craving by cognitive strategies in cigarette smokers.
AB  - Cigarette craving is an important contributor to cigarette smoking, and clinical
      approaches that focus on regulation of craving are effective in reducing rates of
      relapse. However, a laboratory model that targets the use of cognitive strategies
      to regulate craving is lacking. To develop such a model, twenty heavy cigarette
      smokers (>12/day), twenty-two tobacco "chippers" (<6/day), and twenty non-smoking
      controls completed this outpatient study, during which they were presented with
      photographs of cigarettes and foods that have been previously shown to induce
      craving. During each trial, participants were instructed to think of the stimulus
      in one of two ways: by focusing either on the short-term consequences associated
      with consuming the item (e.g., it will taste good) or on the long-term
      consequences associated with regular consumption (e.g., I may get lung cancer).
      Participants reported significantly reduced food cravings when focusing on the
      long-term consequences associated with eating. For cigarette-smoking
      participants, cigarette craving was significantly reduced when focusing on the
      long-term consequences associated with smoking. This latter finding confirms
      clinical data and extends it by highlighting the importance of cognition in the
      modulation of craving. Future studies using this laboratory model could test the
      efficacy of different cognitive strategies and develop targeted interventions for
      smoking cessation based on the regulation of craving.

PMID- 19748192
TI  - Specific antibodies induced by inactivated parapoxvirus ovis potently enhance
      oxidative burst in canine blood polymorphonuclear leukocytes and monocytes.
AB  - We have recently shown that inactivated parapoxvirus ovis (iPPVO) effectively
      stimulates canine blood phagocytes. However, a potential link between innate and
      adaptive immunity induced by iPPVO remained open. The objective of this study was
      to define the effects of repeated iPPVO treatment of dogs to evaluate (i) iPPVO
      specific antibody production, and (ii) modulation of iPPVO-induced oxidative
      burst by anti-iPPVO antibodies. Serum analysis of dogs treated repeatedly with
      iPPVO (Zylexis) showed transient production of non-neutralising iPPVO-specific
      IgG. There was a correlation between iPPVO-specific IgG levels and enhanced
      oxidative burst rates in vitro upon transfer of immune sera. Even four years
      after Zylexis treatment considerably stronger oxidative burst rates in response
      to iPPVO were observed in monocytes and PMN, whereas only moderate burst rates
      were detected in monocytes, but not in PMN, from dogs treated with a placebo.
      Depletion of serum IgG by protein A-sepharose or by parapoxvirus ovis coupled to
      sepharose abolished the increase of oxidative burst responses and resulted in
      burst rates similar to blood leukocytes from control dogs. However, uptake of
      viral particles was found to be independent of iPPVO-specific IgG and restricted
      to cells with dendritic and monocytic morphology. These data demonstrate that non
      neutralising iPPVO-specific IgG is produced during treatment with Zylexis.
      Moreover, for the first time the interaction of iPPVO with antibodies is shown to
      enhance oxidative burst.

PMID- 19748193
TI  - Reconsidering the impact of preterm birth on language outcome.
AB  - BACKGROUND: Since preterm birth is associated with a constellation of pre-, peri-
      and post-natal risk factors, we hypothesised that prematurity may continue to
      impact the development of linguistic abilities even up to the end of the
      preschool years and beyond, giving rise to an atypical developmental trajectory.
      The study tested this hypothesis at six years of age, investigating whether
      language is affected by preterm birth and how different linguistic abilities are
      interrelated. METHOD: Seventy monolingual Italian preterms and 34 age-matched
      controls were recruited. Linguistic abilities (vocabulary, grammar, and
      phonological awareness) as well as general cognitive developmental levels were
      measured. RESULTS: No general cognitive delay emerged, but less developed
      abilities in vocabulary, grammar, and phonological awareness were found in
      preterms compared to fullterms. Moreover, the relations among the different
      linguistic competences differed across groups. CONCLUSIONS: Our study shows that
      even without brain damage, preterm birth continues to affect linguistic
      development up to the end of the preschool years, and probably beyond,
      highlighting a continuity between pre- and peri-natal life and subsequent
      development, and pointing to an atypical developmental trajectory in this
      population compared to fullterms (different rates of development, different
      strategies employed, and differences in the relationships among linguistic
      abilities).

PMID- 19748194
TI  - "The instincts of motherhood: bringing joy back into newborn care".
AB  - Although homo sapiens is equipped with subneocortical neuro-endocrine structures
      comparable to those of all mammals, there is no scientific curiosity about basic
      behaviours such as the maternal protective aggressive instinct or basic emotional
      states such as joy. A study of the fetus ejection reflex is an opportunity to
      present the rational control of the procreative drives as a by-product of human
      brain evolution, and to clarify the concepts of neocortical inhibitions and
      cultural conditioning. After referring to recent spectacular advances, we
      anticipate that in the near future several developing scientific disciplines will
      have the power to overcome the effects of thousands of years of socialisation of
      childbirth.

PMID- 19748195
TI  - Preventing heat-related morbidity and mortality: new approaches in a changing
      climate.
AB  - Due to global climate change, the world will, on average, experience a higher
      number of heat waves, and the intensity and length of these heat waves is
      projected to increase. Knowledge about the implications of heat exposure to human
      health is growing, with excess mortality and illness occurring during hot weather
      in diverse regions. Certain groups, including the elderly, the urban poor, and
      those with chronic health conditions, are at higher risk. Preventive actions
      include: establishing heat wave warning systems; making cool environments
      available (through air conditioning or other means); public education; planting
      trees and other vegetation; and modifying the built environment to provide proper
      ventilation and use materials and colors that reduce heat build-up and optimize
      thermal comfort. However, to inspire local prevention activities, easily
      understood information about the strategies' benefits needs to be incorporated
      into decision tools. Integrating heat health information into a comprehensive
      adaptation planning process can alert local decision-makers to extreme heat risks
      and provide information necessary to choose strategies that yield the largest
      health improvements and cost savings. Tools to enable this include web-based
      programs that illustrate effective methods for including heat health in
      comprehensive local-level adaptation planning; calculate costs and benefits of
      several activities; maps showing zones of high potential heat exposure and
      vulnerable populations in a local area; and public awareness materials and
      training for implementing preventive activities. A new computer-based decision
      tool will enable local estimates of heat-related health effects and potential
      savings from implementing a range of prevention strategies.

PMID- 19748196
TI  - [Management of large villous tumors of the lower part of the rectum].
AB  - Radical surgery (i.e. rectal resection) remains the gold standard for surgical
      management of large villous tumours but such a strategy is associated with
      potential postoperative complications with high risk of functional disorders and
      genito-urinary dysfunction. Transanal local surgery is an alternative treatment
      with low morbidity. A new procedure as transanal endoscopic microsurgery can be
      proposed to achieve local complete excision of rectal tumours especially in the
      middle and upper parts of the rectum lesions unresectable by conventional local
      surgery. For malignant tumours, accurate pathological evaluation to define
      histopathological criteria must be done to propose or not additional radical
      surgery.

PMID- 19748197
TI  - Percutaneous balloon dilatation of stenotic calyceal diverticular infundibula in
      patients with recurrent urinary tract infections.
AB  - AIM: Renal calyceal diverticula are usually detected as incidental findings on
      intravenous pyelograms (IVPs) and rarely manifest any clinical signs or symptoms.
      However, they can interfere with patient's quality of life in a number of
      instances causing pain, recurrent urinary tract infections (UTIs), abscess,
      systemic sepsis and calculus formation. The purpose of this study was to review
      the clinical indications, procedure technique and clinical outcome in all
      patients referred to Interventional Radiology for the percutaneous management of
      renal calyceal diverticula. MATERIALS AND METHODS: A retrospective review of all
      patients treated with percutaneous balloon dilatation of calyceal diverticular
      infundibula in the Interventional Radiology Department over a 10-year period was
      performed. Data collected included clinical details, laboratory indices, IVP and
      CT findings, procedure details and clinical outcome. RESULTS: A total of three
      patients were treated over the course of the study period. All patients were
      young females who presented as a result of recurrent urinary tract infections.
      The calyceal diverticula were diagnosed incidentally on routine IVPs, with CT
      eloquently confirming the plain film findings in two cases. Technical procedure
      success was achieved in all cases, avoiding surgical intervention. Clinical
      follow-up revealed no further UTIs following dilatation. CONCLUSION: Fluoroscopic
      guided percutaneous balloon dilatation of renal calyceal diverticular infundibula
      following direct diverticular puncture is a safe and well tolerated method to
      reduce UTI and potentially avoid future stone formation.

PMID- 19748198
TI  - Natural bioactive compounds of Citrus limon for food and health.
AB  - Citrus genus is the most important fruit tree crop in the world and lemon is the
      third most important Citrus species. Several studies highlighted lemon as an
      important health-promoting fruit rich in phenolic compounds as well as vitamins,
      minerals, dietary fiber, essential oils and carotenoids. Lemon fruit has a strong
      commercial value for the fresh products market and food industry. Moreover, lemon
      productive networks generate high amounts of wastes and by-products that
      constitute an important source of bioactive compounds with potential for animal
      feed, manufactured foods, and health care. This review focuses on the
      phytochemistry and the analytical aspects of lemon compounds as well as on the
      importance for food industry and the relevance of Citrus limon for nutrition and
      health, bringing an overview of what is published on the bioactive compounds of
      this fruit.

PMID- 19748199
TI  - Emergence of multiresistant variants of the community-acquired methicillin
      resistant Staphylococcus aureus lineage ST1-SCCmecIV in 2 hospitals in Rio de
      Janeiro, Brazil.
AB  - Usually, community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA)
      is susceptible to a variety of non-beta-lactam drugs. These isolates commonly
      display SCCmecIV and are associated with community-acquired infections. More
      recently, CA-MRSA has been isolated from health-care-associated diseases. We
      characterized MRSA isolates from 2 hospitals in Rio de Janeiro area to assess the
      entry of new lineages. The isolates were primary genotyped using a combination of
      molecular typing methods including SCCmec, restriction modification test, and
      Panton-Valentine leukocidin (PVL) detection. Pulsed-field gel electrophoresis was
      carried out for representatives of each lineages found. Disk diffusion test was
      performed as recommended by the Clinical and Laboratory Standards Institute.
      SCCmecIV was the predominant cassette mec detected. The most frequent MRSA
      lineage, a PVL nonproducer, was allocated in the CC1-SCCmecIV. It was found that
      56% of these isolates were resistant to 3 or more non-beta-lactam drugs.
      Multilocus sequence typing of a representative of the CC1 isolates supported our
      finds that multiresistant variants of a CA-MRSA lineage (ST1-SCCmecIV) emerged in
      this city.

PMID- 19748200
TI  - Traffic law knowledge disparity between Hispanics and non-Hispanic whites in
      California.
AB  - BACKGROUND: The Hispanic population is one group that is involved in a
      disproportionately high percentage of fatal motor vehicle collisions in the
      United States. STUDY OBJECTIVES: This study investigated demographic factors
      contributing to a lack of knowledge and awareness of traffic laws among Hispanic
      drivers involved in motor vehicle collisions (MVCs) in southern California.
      METHODS: The cross-sectional study enrolled adults (n = 190) involved in MVCs
      presenting to a Level I trauma center in southern California over a 7-month
      period. Subjects completed a survey about California traffic law knowledge (TLK)
      consisting of eight multiple-choice questions. The mean number of questions
      answered correctly was compared between groups defined by demographic data.
      RESULTS: The mean number of TLK questions answered correctly by Hispanic and non
      Hispanic white groups were significantly different at 4.13 and 4.62, respectively
      (p = 0.005; 95% confidence interval -0.83 to -0.15). Scores were significantly
      lower in subjects who were not fluent in English, had less than a high school
      education, did not possess a current driver's license, and received their TLK
      from sources other than a driver's education class or Department of Motor Vehicle
      materials. Analysis of variance showed that the source of knowledge was the
      strongest predictor of accurate TLK. CONCLUSION: Source of TLK is a major
      contributing factor to poor TLK in Hispanics. An emphasis on culturally specific
      traffic law education is needed.

PMID- 19748201
TI  - Faculty and medical students' perceptions of teaching and learning about the
      doctor-patient relationship.
AB  - OBJECTIVE: To explore student and faculty perceptions of how students are
      learning doctor-patient relationship skills in their clinical medical education.
      METHODS: Exploratory qualitative study involving data from interviews and focus
      groups with students and interviews with teaching faculty. RESULTS: Respondents
      reported that pre-clinical relationship skills curricula were not well
      coordinated with clinical curricula. Within the clinical curriculum, respondents
      perceived a disparity between general practice and hospital-based attachments.
      Teaching of relationship skills on the wards was highly variable, rarely
      explicit, and primarily dependent on role-modelling. In contrast, general
      practice runs included explicit teaching with feedback that reinforced skills
      taught in the pre-clinical curriculum. Respondents recommended increased focus on
      and assessment of students' interpersonal skills within clinical settings.
      CONCLUSION: Pre-clinical and clinical relationship skills curricula were not
      coordinated. The tension between service commitments and student teaching in
      hospital-based attachments contributed to an insufficient focus on communication
      and relationship skills acquisition and did not reinforce teaching in pre
      clinical and ambulatory clinical settings. PRACTICE IMPLICATIONS: The teaching of
      doctor-patient relationship skills can be augmented by coordinating pre-clinical
      and clinical curricula and by requiring observation and structured feedback
      related to explicit criteria of student skills acquisition across all clinical
      learning experiences.

PMID- 19748202
TI  - Awareness and use of practice guidelines on medical end-of-life decisions in
      Dutch hospitals.
AB  - OBJECTIVE: To describe awareness, use and supportiveness for physicians of three
      practice guidelines on medical end-of-life decisions, and to identify factors
      associated with increased awareness of these guidelines. METHODS: Questionnaires
      were sent to 793 physicians from 12 hospitals in 2005 (response 52%). RESULTS:
      Most physicians were aware of the existence of the practice guidelines for
      euthanasia (75%) and do-not-resuscitate decisions (63%), and 35% were aware of
      the existence of the guidelines for palliative sedation. Physicians who had read
      the guidelines and had been in a situation in which they had to consider a
      euthanasia request, 88% had used the guidelines for euthanasia; corresponding
      figures are 92% for do-not-resuscitate and 100% for palliative sedation. When
      used, almost all physicians felt the guideline had been supportive. More positive
      attitudes towards guidelines and involvement in guideline development were
      associated with increased awareness of the presence of guidelines. CONCLUSION: It
      appears that practice guidelines on medical end-of-life decisions are useful for
      physicians: when they are aware of the presence of such guidelines in their
      institution, they gain support when using them. PRACTICE IMPLICATIONS: Health
      care institutions should be encouraged to disseminate guidelines among
      caregivers, and also involve them in the development of the guidelines.

PMID- 19748203
TI  - The relation between patient-centeredness and patient empowerment: a discussion
      on concepts.
AB  - OBJECTIVE: The concepts of patient-centeredness and patient empowerment offer
      opportunities for patients to increase their autonomy and involvement in their
      care and treatment. However, these concepts appear to be understood in different
      ways by professional groups involved in healthcare and research. To optimize
      understanding there is a need to create a common language. To explore and compare
      the concepts of patient-centeredness and patient empowerment, and clarify a
      possible relationship between the two from the perspective of the encounter
      between patients and their healthcare providers. METHODS: Concept analysis
      approach in which the concepts are compared based on literature review. RESULTS:
      Patient-centeredness can be the goal of an encounter between patient and
      caregiver. As a process, it is of great value in the process of patient
      empowerment. Patient empowerment appears to be broader than patient-centeredness,
      and may place greater demands on caregivers and the organisation of healthcare.
      CONCLUSION: Patient-centeredness and patient empowerment are complementary
      concepts which do not oppose one-another. Patient empowerment can be achieved by
      patient-centeredness, but patients can also empower themselves. PRACTICE
      IMPLICATIONS: Clarification of patient-centeredness and patient empowerment can
      facilitate their use by those involved in healthcare, improve the quality of
      healthcare, and aid future research.

PMID- 19748204
TI  - From information processing to behavioral intentions: exploring cancer patients'
      motivations for clinical trial enrollment.
AB  - OBJECTIVE: To investigate cancer patients' motivations for clinical trial
      enrollment, this study tests the proposition that a model of Risk Information
      Seeking and Processing (RISP) could serve as an antecedent to the Theory of
      Planned Behavior (TPB). METHODS: With data from a telephone survey, we examined
      whether components of the RISP model had significant impact on belief-based
      attitudes and behavioral intentions. RESULTS: Risk judgment and affective
      responses, especially optimistic feelings, consistently related to attitudes and
      behavioral intentions. Trust in doctors also significantly related to our
      respondents' positive attitudes toward clinical trials. CONCLUSION: The RISP
      model might have more constrained applicability as compared to the TPB in
      explaining cancer patients' motivations for clinical trial enrollment. However,
      certain components of the RISP model seemed to contribute to our respondents'
      attitude formation as interesting additions to the TPB. PRACTICE IMPLICATIONS:
      Communication about clinical trials is a balance act between providing sufficient
      information about the potential risks and benefits involved in a clinical trial
      and managing emotional responses that cancer patients associate with
      participation. Both acts contribute to the formation of positive attitudes toward
      clinical trials among cancer patients, which is the driving force behind their
      intentions for clinical trial enrollment.

PMID- 19748205
TI  - Barriers to effective self-management in cardiac patients: the patient's
      experience.
AB  - OBJECTIVE: This paper identifies common obstacles impeding effective self
      management among patients with heart disease and explores how for disadvantaged
      patients access barriers interfere with typical management challenges to
      undermine patients' efforts to care for their illnesses. METHODS: We convened 33
      focus group discussions with heart patients in 10 U.S. communities. Using content
      analysis, we identified and grouped the most common barriers that emerged in
      focus group discussions. RESULTS: We identified nine major themes reflecting
      issues related to patients' ability to care for and manage their heart
      conditions. We grouped the themes into three domains of interest: (1) barriers
      that interfere with getting necessary services, (2) barriers that impede the
      monitoring and management of a heart condition on a daily basis, and (3) supports
      that enable self-management and improve care. CONCLUSION: For disadvantaged
      populations, typical problems associated with self-management of a heart
      condition are aggravated by substantial obstacles to accessing care. PRACTICE
      IMPLICATIONS: Ensuring disadvantaged patients with chronic heart conditions are
      linked to formal systems of care, such as cardiac rehabilitation programs, could
      better develop patients' self-management skills, reduce barriers to receiving
      care and improve the overall health outcomes of these patients.

PMID- 19748206
TI  - Postresection survival outcomes of pancreatic cancer according to demographic
      factors and socio-economic status.
AB  - AIM: Aim of the study was to evaluate the impact of demographic factors (DGF) and
      socio-economic status (SES) on survival after pancreatic cancer resection in a
      German setting. METHODS: Patients with pancreatic adenocarcinoma and
      pancreaticoduodenectomy were identified from our pancreatic resection database
      (1989-2008). DGF, SES, survival and tumor-related information were obtained from
      hospital records, a registry office questionnaire, and telephone interviews with
      patients, relatives and general practitioners. RESULTS: Follow-up was completed
      in 117 patients. Median overall survival and 5-year survival rate was 22 month
      and 10%, respectively. Survival significantly improved over time with a 16% 5
      year survival and a median survival of 27 month for recent patients. The longest
      survival period with a median of 63 month was observed for patients with AJCC
      stage I. Tumor-related factors and treatment period, but not SES influenced
      survival after pancreatic cancer resection in our cohort. CONCLUSIONS: To our
      knowledge, this is the first study to explore survival from pancreatic cancer
      according to DGF and SES in a German setting. Disparities in survival among our
      patients depend solely on tumor-related factors and treatment period and could
      not be explained by SES including key factors like income or type of health
      insurance. The comparable postresection outcome of patients with low and high SES
      at our department could be in part due to the universal German multi-payer health
      system, based on compulsory enrolment for the majority, which seems not to
      support health care inequalities seen in other OECD countries.

PMID- 19748207
TI  - Effect of total knee arthroplasty on metabolic syndrome.
AB  - The purpose of this study was to evaluate the effect of changing activity after
      total knee arthroplasty (TKA) on metabolic syndrome with a follow-up period of 2
      years. Two hundred consecutive patients who were to undergo TKA were
      prospectively enrolled. The patients' blood pressure, fasting plasma glucose
      level, the lipid profile, the waist circumference, the Knee Society score, and
      the Lower Extremity Activity Scale were measured preoperatively and at the 2-year
      follow-up visit. The data from 169 patients were finally collected and reviewed.
      Two years after primary TKA, there was no change in the prevalence of metabolic
      syndrome, despite that the patients had a significant increase of their physical
      activity.

PMID- 19748208
TI  - Revision of failed total hip arthroplasty acetabular cups to porous tantalum
      components: a 5-year follow-up study.
AB  - We reviewed 263 consecutive patients with failed acetabular components after
      total hip arthroplasty that were revised using porous tantalum acetabular
      components and augments when necessary. The mean follow-up was 73.6 months
      (range, 60-84 months). The improvement of mean Harris hip score, Western Ontario
      and McMaster Osteoarthritis Index, and University of California Los Angeles
      activity scales were statistically significant (P < .001). Subjective assessments
      showed that 87.3% of patients reported "improvement" and 85.9% were "very or
      fairly pleased" with the results. At the most recent follow-up, all acetabular
      components were radiographically stable and none required rerevision for
      loosening. The acetabular revision was considered successful in 87% of cases.
      From this study, we conclude that the acetabular component used was reliable in
      creating a durable composite without failure for a minimum of 5 years.

PMID- 19748209
TI  - An empirical test of the metacognitive model of obsessive-compulsive symptoms:
      replication and extension.
AB  - The aim of the current study was to further investigate the role of metacognitive
      beliefs implicated in Wells' (1997) model of obsessive-compulsive disorder (OCD).
      The metacognitive domains of thought-fusion beliefs and beliefs about rituals
      were positively correlated with obsessive-compulsive symptoms in a community
      control sample (N=269) and in an OCD sample (N=57). The OCD sample had
      significantly more obsessive-compulsive symptoms as well as higher scores on the
      metacognitive constructs than the control sample. In order to perform a more
      stringent test of the metacognitive model of OCD and to explore the role of a
      third metacognitive construct, that of stop signals, a second study was conducted
      using a community control sample (N=304). All three metacognitive constructs were
      positively correlated with obsessive-compulsive symptoms. Thought-fusion beliefs
      and beliefs about rituals predicted obsessive-compulsive symptoms, even when
      controlling for worry, threat, and non-metacognitive beliefs such as
      perfectionism/certainty and responsibility. Results of this study provide further
      evidence for the importance of metacognitions in OCD.

PMID- 19748210
TI  - Retroperitoneal approach to abdominal aortic aneurysm repair preserves splanchnic
      perfusion as measured by gastric tonometry.
AB  - BACKGROUND: We investigated if minimizing bowel manipulation and mesenteric
      traction using the retroperitoneal approach in open abdominal aortic aneurysm
      (AAA) repair preserves splanchnic perfusion, as measured by gastric tonometry,
      and reduces the systemic inflammatory response and dysfunction of the various
      organs. METHODS: Patients undergoing elective AAA repair were randomized into
      three groups. Group I had repair via the retroperitoneal approach, while groups
      II and III were repaired via the transperitoneal approach with the bowel packed
      within the peritoneal cavity or exteriorized in a bowel bag, respectively. A
      tonometer was used to measure gastric intramucosal pH (pHi), as an indicator of
      splanchnic perfusion, just prior to aortic clamping, during clamping, and at 0.5,
      1, 2, 4, 6, and 12 hr after clamp release. Multiorgan dysfunction syndrome (MODS)
      and systemic inflammatory response syndrome (SIRS) scores were calculated and
      systemic interleukins (IL-6 and IL-10) measured at predetermined intervals.
      RESULTS: Thirty-four patients were successfully randomized. The gastric pHi was
      significantly lower in group II (n=12) and group III (n=11) compared to group I
      (n=11) during aortic clamping and immediately after clamp release (p<0.05). The
      aortic clamp time, blood loss, MODS and SIRS scores, and systemic cytokine
      response were similar in all three groups. When the three groups were combined,
      there were significant positive correlations between the operation time, aortic
      clamp time, and amount of blood lost and transfused with plasma IL-6 levels and
      MODS score on the first postoperative day. CONCLUSION: The retroperitoneal
      approach for open AAA repair is associated with gastric tonometric evidence of
      better splanchnic perfusion compared to the transperitoneal approach.

PMID- 19748211
TI  - Protective effect of etomidate on spinal cord ischemia-reperfusion injury induced
      by aortic occlusion in rabbits.
AB  - BACKGROUND: We conducted a randomized controlled study on the neuroprotective
      effect of a commonly used anesthetic, etomidate, in an ischemia-reperfusion (IR)
      injury rabbit model. METHODS: We studied 24 white adult Japanese rabbits at the
      animal facility at the Medical College of Wuhan University. Rabbits were randomly
      assigned into a sham-operation group (group I), an IR group (group II), and an
      etomidate-treated IR group (group III). Rabbits in groups II and III were
      subjected to 45 min of infrarenal aortic cross-clamping to induce spinal cord
      ischemia, while group I rabbits received the sham operation as a control.
      Following an initial single-dose intravenous injection at 0.6 mg/kg 10 min before
      aortic clamping, etomidate was infused intravenously at 3mg/(kg . hr) in group
      III rabbits until unclamping, while 0.9% saline was given as the control in group
      II. RESULTS: Changes in neurological function scores, histopathology,
      electromyography, malondialdehyde levels, superoxide dismutase activities, and
      the concentrations of Ca(2+), Mg(2+), Cu(2+), and Zn(2+) ions were measured.
      Compared with the sham-operation group, group II showed significant IR injury
      associated changes in all parameters evaluated (p<0.01), whereas these
      unfavorable changes were significantly reversed in etomidate-treated animals
      (p<0.05 or p<0.01). No significant differences were observed between group I and
      group III animals in all parameters. CONCLUSION: Etomidate displayed a potent
      neuroprotective effect against IR-induced spinal cord injuries. We propose that
      this effect may be associated with the ability of etomidate to enhance the
      activities of endogenous antioxidants and maintain the ion balance in IR-affected
      tissues.

PMID- 19748212
TI  - Use of a new endovenous laser device: results of the 1,500 nm laser.
AB  - BACKGROUND: A new endovenous laser wavelength (1,500 nm diode laser) in the
      treatment of great saphenous vein (GSV) reflux was evaluated. We studied the
      occlusion rate at 6 months and noted possible side effects. METHODS: In 129
      patients, 158 GSVs were treated using the 1,500 nm diode laser. An average linear
      endovenous energy density of 53.4 J/cm and an average endovenous fluence of 32.21
      J/cm(2) were administrated to the vein. RESULTS: The occlusion rate at 6 months
      postoperative was 93.3%. Some of the nonoccluded veins closed spontaneously. A
      postoperative foam treatment was necessary in 3.4% of the treated veins. We found
      a marked shrinkage of the treated veins. There were limited side effects:
      moderate or severe ecchymosis in 19%, moderate pain in 1%, moderate periphlebitis
      in 8.2%, with no paresthesias. CONCLUSION: Endovenous laser treatment of the GSV
      using a 1,500 nm diode laser is effective and safe. The marked shrinkage of the
      treated veins can guarantee good long-term results.

PMID- 19748213
TI  - Use of internal endoconduits as an adjunct to endovascular aneurysm repair in the
      setting of challenging aortoiliac anatomy.
AB  - The combination of Trans-Atlantic Intersociety Consensus (TASC) D aortoiliac
      occlusive disease as well as a symptomatic abdominal aortic aneurysm (AAA) is not
      a common occurrence. Extensive calcified atherosclerotic disease, occlusions, and
      small iliofemoral segmental arteries make transfemoral access difficult, if not
      impossible, for endovascular aneurysm repair (EVAR) in these patients. We present
      a case in which "controlled rupture" of the external iliac artery with a covered
      stent allowed transfemoral delivery of an aortouni-iliac stent graft with a
      completion femoral-to-femoral bypass. The patient is a 60-year-old male with a
      5.3 cm symptomatic infrarenal AAA and a history of one block right leg
      claudication. Preoperative computed tomography angiography revealed the patient
      to have occlusion of the right common iliac artery, extensive calcified stenoses
      of his aortoiliac segments, and a prohibitively small left external iliac artery,
      which measured 4.5 mm at its narrowest diameter. The patient, despite discussions
      concerning the suitability of his iliac arteries as conduits for the delivery of
      the stent graft, insisted on an endovascular approach to lessen his chances of
      postoperative sexual dysfunction as well as minimize his length of stay. Access
      was obtained through bilateral femoral artery cutdowns, and attempts at dilating
      the left external iliac artery using 16-French dilators were performed without
      success. An 8 mm x 5 cm covered self-expanding stent was deployed in the diseased
      4.5 mm left external iliac artery, followed by angioplasty performed with an 8 mm
      noncompliant balloon to disrupt the vessel. This endoconduit now allowed
      accommodation of our 18-French introducer for the aortouni-iliac stent graft. The
      operation was completed with a femoral-femoral bypass. Flow to both hypogastric
      arteries was preserved. We believe use of such techniques will ultimately expand
      the number of patients eligible for EVAR and avoid devastating access-related
      complications.

PMID- 19748214
TI  - Implications of in situ thrombosis and distal embolization during superficial
      femoral artery endoluminal intervention.
AB  - BACKGROUND: Endoluminal therapy for superficial femoral artery (SFA) occlusive
      disease is commonplace, but the incidence and outcomes of in situ thrombosis
      (IST) and distal embolization (DE) have not been well defined. The aim of this
      study was to examine the impact of IST and DE on long-term outcomes of SFA
      interventions. METHODS: A database of patients undergoing endovascular treatment
      of the SFA was queried. Patients who developed either IST treated by
      pharmacomechanical lytic therapy or DE were selected and compared to those
      without either event (control). Kaplan-Meier survival analyses were performed to
      assess time-dependent outcomes, with 2-year outcomes reported. Factor analyses
      were performed using a Cox proportional hazard model for time-dependent
      variables. RESULTS: There were 818 limbs that underwent endovascular treatment
      for symptomatic SFA disease (59% for claudication and 41% rest pain and tissue
      loss). In the control group, 69% underwent angioplasty, 16% underwent primary
      stenting, and 15% underwent laser/directional atherectomy. In the IST group,
      these numbers were 41%, 28%, and 31%, respectively, while in the DE group they
      were 35%, 32%, and 33%, respectively. Overall the rates were 7.3% with 3.5%
      suffering IST (all treated with lytic therapy) and 3.8% suffering DE (68% treated
      percutaneously and the remainder treated by embolectomy). Females were more
      likely to experience either event. Compared to the control group, only one-third
      of the patients who suffered DE had primary angioplasty, while the remainder
      underwent primary stenting or laser/directional atherectomy. There was no
      difference in primary, assisted primary, or secondary patency rates between the
      control and DE groups. DE resulted in significantly lower limb salvage (87 + or -
      2% vs. 68 + or - 8%, control vs. DE, p<0.05) and freedom from recurrent symptoms
      (73 + or - 2% vs. 69 + or - 8%, control vs. DE, p<0.05), while IST treated with
      lytic therapy was associated with lower patency (67 + or - 2% vs. 37 + or - 6%
      primary, 77 + or - 2% vs. 41 + or - 9% assisted primary, and 79 + or - 2% vs. 44
      + or - 9%, secondary, control vs. IST, p<0.01). There was no difference in
      outcomes based on whether surgical or percutaneous therapy was used to treat DE.
      While preoperative tibial runoff did not influence limb loss after DE, it was
      significantly associated with decreased patency after IST. CONCLUSION: DE during
      SFA interventions is associated with limb loss independently of preoperative
      runoff and subsequent intervention while the use pharmacomechanical lytic therapy
      for IST is associated with loss of patency but equivalent limb salvage and
      freedom from recurrent symptoms.

PMID- 19748215
TI  - Application of shape memory alloy pressure-controlled vascular clamp for
      atraumatic vessel occlusion.
AB  - BACKGROUND: To realize atraumatic vessel occlusion, a new hemostatic clamp using
      superelastic shape memory alloy (SMA) as a pressure control limiter has been
      proposed. It was designed taking advantage of a unique mechanical property of
      SMA. The ability to control pressure with the newly designed SMA clamp was
      investigated. The traumatic effect on vessel walls was evaluated in order to
      confirm the SMA clamp's biological effect of protecting vessels from damage.
      METHODS: Twenty-four pig thoracic aortas were divided into four groups: SMA group
      1 (0.3mm diameter SMA wire used), SMA group 2 (0.4mm diameter SMA wire used),
      base model group (hemostatic clamp of Mimura type), and a control group. The
      biomechanical interaction between the pressure-controlled clamp and animal aortas
      was evaluated with a micropressure analyzing system. The atraumatic effect of the
      SMA clamp was examined on pig thoracic aortas in vitro and compared with that of
      its base model. The morphological injury of each vessel was evaluated after being
      clamped for 15 min. RESULTS: Pressure saturation was shown in the displacement
      pressure curve of the SMA clamp. In both SMA group 1 and SMA group 2, except for
      a slight imprint of compression in the intima, no obvious injury was observed,
      while in the base model group the endothelial laceration was observed when the
      clamp was closed to notch I. More serious injuries in the endothelial intima and
      media were observed when the clamp was closed to notches II and III. CONCLUSION:
      The effect of pressure-controlling SMA clamps on the in vitro vessel model was
      evaluated. Histological observation and the traumatic score proved that the
      safety of the clamps was improved with the new design of pressure control. This
      technique supplies an effective and applicable way of realizing atraumatic
      clamping.

PMID- 19748216
TI  - The impact of a systemwide policy for emergent off-hours venous duplex ultrasound
      studies.
AB  - BACKGROUND: We evaluated the impact of an after-hours policy regulating venous
      duplex ultrasound (VDU) for deep vein thrombosis (DVT) diagnosis on resource
      utilization and patient care. METHODS: On July 1, 2007, we altered the approach
      to emergent VDU of patients with potential DVT during off-hours (defined as 5:00
      p.m. to 7:00 a.m. weekdays, after 3:30 p.m. Saturdays and Sundays). Instead of 24
      hr access, we permitted a venous duplex study in the noninvasive vascular
      laboratory (NIVL) only after meeting set criteria developed collaboratively
      across services. In the emergency department (ED), we based all VDU requests on a
      preset modified Wells score (MWS) as determined by the ED physician. Those
      patients with MWS 0 or 1 and those above 1 who could receive empiric single-dose
      low-molecular weight heparin (LMWH) received next-morning imaging unless
      consultation with a vascular surgeon created an emergent imaging plan. In
      parallel, inpatient emergent VDU was permitted only after contact with an
      attending vascular surgeon and where empiric short-term anticoagulation could not
      occur safely. We tracked NIVL utilization, patient morbidity, sonographer
      retention, and satisfaction. RESULTS: The number of overall off-hours emergent
      VDUs decreased from 59 to 19/month after implementation. Testing was deferred in
      52 ED patients: 15 stayed in the ED for testing in the morning and 37 were
      discharged to be tested the following day. Thirty-one of 37 patients returned for
      testing as outpatient follow-up. Twenty-eight received ED LMWH while awaiting
      testing. No adverse events were noted with the delay. The mean MWS for ED after
      hours studies was 2.9+/-1.6 and that for deferred ER studies was 2.4+/-1.3
      (p=0.005). Incidentally, overall off-hours inpatient and ED VDU requests
      decreased 64% with no clinical adverse events in the first year. The rate of
      overall positive studies done off-hours increased from 6.7% to 20% (p<0.0001).
      Sonographer satisfaction was maintained with regulation of call. CONCLUSION: Our
      collaborative approach allowed off-hour VDU utilization to decrease without any
      measurable negative care impact.

PMID- 19748217
TI  - Femoral artery complications after cardiac catheterization: a study of patient
      profile.
AB  - BACKGROUND: Femoral artery complications after cardiac catheterization range from
      simple events to severe complications requiring invasive techniques or surgery
      with significant economic costs. This study evaluated early femoral arterial
      complications from percutaneous arterial access during diagnostic and
      interventional cardiac catheterizations in an era of widespread use of closure
      devices and intense anticoagulation. METHODS: Patients undergoing percutaneous
      cardiac catheterization via the femoral artery between August 2005 and December
      2005 were identified using an ICD-9 patient database. Forty-six data points were
      extracted by retrospective chart review, including demographics, comorbidities,
      type of anticoagulation, procedural details, and postprocedural complications.
      Univariable analysis and binary logistic regression were used to determine
      factors associated with complications. RESULTS: Eighty-two of 579 patients (14%)
      suffered complications. The most common complications were hematomas (51
      patients, 10%) and active bleeding (14 patients, 2.4%). Closure devices were used
      in 470 patients. After multivariable correction, use of preprocedural (odds ratio
      [OR]=5.65, 95% confidence interval [CI] 2.58-12.3, p<0.001) and intraprocedural
      (OR=4.88, 95% CI 1.95-12.3, p<0.001) antithrombotic agents (antiplatelet and/or
      anticoagulants), intraprocedural clopidogrel (OR=2.98, 95% CI 1.21-7.30,
      p=0.017), and postprocedural heparin (OR=29.4, 95% CI 3.56-250, p=0.002) were
      associated with increased risk. Coronary artery disease was associated with
      increased risk (OR=11.1, 95% CI 4.78-25.6, p<0.001), while use of a closure
      device (OR=0.263, 95% CI 0.125-0.553, p<0.001), male gender (OR=0.421, 95% CI
      0.220-0.805, p=0.009), and prior catheterization (OR=0.033, 95% CI 0.012-0.095,
      p<0.001) were protective. CONCLUSION: With increasing numbers of complex coronary
      endovascular procedures and widespread use of high-dose multidrug antithrombotic
      therapy, femoral artery injuries will continue to be a significant risk for
      patients. Postprocedural monitoring with a high level of suspicion and use of
      vascular closure devices in high-risk patients may decrease the incidence of
      femoral artery complications. The use of vascular closure devices after low-risk
      procedures in male patients or those with previous ipsilateral catheterization
      might not be warranted but needs further study.

PMID- 19748218
TI  - Endovascular treatment of external iliac artery stenoses for claudication with
      systematic stenting.
AB  - The results of the endovascular treatment of external iliac artery lesions in
      patients with claudication are not well known. In the literature, very often, the
      studied populations are not homogenous (people with claudication and with acute
      ischemia) and the external iliac artery is not differentiated from the primary
      iliac artery. Moreover, systematic stenting is still debated. Our goal was to
      study the results of systematic stenting for atheromatous lesions of the external
      iliac artery in a consecutive and homogenous population of patients with
      claudication. From June 2000 to December 2006, 90 external iliac arteries were
      treated with systematic stenting for atheromatous lesions in 81 consecutive
      patients with claudication (74 men and 7 women, aged 62+/-12 years). Lesions were
      classified according to the Trans-Atlantic Intersociety Consensus (TASC).
      Endovascular treatment was systematically chosen for TASC A (n=40) and B (n=30)
      patients and patients at high surgical risk for TASC C (n=18) and D (n=2). One
      hundred and seven stents were placed; they were 37+/-21 mm long with a 7+/-0.6mm
      diameter. Clinical examination and duplex follow-up were carried out at a minimum
      of 3 months and at the end of the follow-up. There was a 2.2% complication rate,
      without any deaths (retroperitoneal hematoma). Mean follow-up was 23 months (with
      a 13-month median). Primary patency rate was 97% (standard error [SE] 2%) at 1
      year, 90% (SE 4.6%) at 2 years, and 84% (SE 6.6%) at 3 years. Secondary patency
      rate was 98% (SE 1.5%) at 1 year, 93% (SE 3.9%) at 2 years, and 93% (SE 4.5%) at
      3 years. Ten restenoses were detected and treated by endovascular techniques
      (n=6), bypass (n=2), or medication (n=2). At the end of the follow-up, the
      patients were asymptomatic (n=62) or presented with a moderate (n=17) or severe
      (n=8) claudication. A patient with hemodialysis was amputated at the metatarsal
      level. No significant predictive restenosis factor was discovered. However, the C
      or D TASC classification seemed to favor an earlier restenosis (p=0.06). In
      conclusion, our study demonstrates that, in a larger population than in the
      literature, systematic stenting on the external iliac artery gives satisfying
      results in patients with claudication.

PMID- 19748219
TI  - Tolerable hemodynamic changes after femoral artery ligation for the treatment of
      infected femoral artery pseudoaneurysm.
AB  - BACKGROUND: We analyzed the hemodynamic changes induced by femoral artery
      ligation with concomitant thrombectomy in intravenous drug abusers with infected
      femoral artery pseudoaneurysm (IFAP) and their clinical significance. METHODS:
      Between January 2000 and November 2007, a total of 55 patients presented to our
      clinic with IFAP. Among these patients, 54 were treated by femoral artery
      ligation with concomitant thrombectomy. Open collateral circulations were
      assessed by intraoperative angiography, including detection of mean artery
      pressure (MAP) of back-flow from the profunda femoris artery and the superficial
      femoral artery after operation. Patients were followed up for 3-72 months (mean
      35). The data were then subjected to statistical analysis. RESULTS: Preoperative
      death occurred in one patient due to acute onset of drug addiction in the ward.
      Preoperatively, massive necrosis developed in the left limb of the only patient
      with bilateral IFAPs. All 54 patients underwent femoral artery ligation with
      concomitant thrombectomy, including nine cases of ligation of the external iliac
      artery and one case of above-knee limb amputation. All wounds were completely
      healed within 3 months. Six late deaths (11.1%), resulting solely from refractory
      drug addiction, were observed during the follow-up period, of which two occurred
      2 years, one 4 years, and three 5 years postoperatively. No toe amputations were
      noted during the follow-up period. Fourteen patients (25.9%) developed
      intermittent claudication. One postoperative limb was lost. Of all 54 patients,
      38 were subjected to collateral circulation assessment by intraoperative
      angiography. Collateral circulations were found well open in a baseline path with
      four stations down to the distal lower limbs of all assessed patients. Four
      preferred types of iliac-femoral collaterals were defined. Postoperatively,
      compared to the external iliac artery, the MAP levels of back-flow from the
      profunda femoris artery and the superficial femoral artery significantly dropped
      to 43.89+/-2.75 and 18.08+/-2.76 mm Hg, respectively. CONCLUSION: As a result of
      femoral artery ligation without reconstruction, well open collateral circulations
      and acceptable distal arterial runoff blood are seen, which suggests that this
      procedure is a reliable alternative to the emergent treatment of IFAPs in drug
      addicts. However, arterial reconstruction may be used as a backup approach if
      necessary during observation.

PMID- 19748220
TI  - Renal artery stent infection and pseudoaneurysm management.
AB  - BACKGROUND: Infection of a renal artery stent and pseudoaneurysm is extremely
      uncommon, with four reports in the literature. We present a fifth case and the
      complex management resulting in kidney salvage. METHODS AND RESULTS: A 56-year
      old female underwent right renal artery stenting for hypertension.
      Postoperatively, she developed methicillin-resistant Staphylococcus infection,
      treated with antibiotics. Eight-month follow-up duplex ultrasound revealed a
      right renal artery pseudoaneurysm just distal to the stent. Computed tomography
      angiography (CTA) showed 2.8 cm proximal and 4.2 cm distal mycotic aneurysms.
      Antibiotics and planning angiogram were prescribed. A Chevron incision and
      duodenal kocherization were employed. The aorta below the superior mesenteric
      artery and below the renal vein was mobilized, as were the right renal artery and
      vein, hepatic artery, and saphenous vein. Following heparinization, the aorta was
      cross-clamped, as was the right renal artery at the hilum. The kidney was infused
      with cold saline. The renal artery stent was explanted, and aneurysmectomy was
      performed. The renal artery ostium was oversewn. A renal artery to hepatic artery
      saphenous vein bypass was fashioned, and patency was confirmed with
      intraoperative duplex ultrasound. Postoperatively, creatinine was normal, renal
      scan showed the right kidney to be functional, and duplex ultrasound showed a
      patent bypass graft. The patient was discharged on postoperative day 11 on long
      term antibiotics. Eight-month follow-up duplex and CTA showed a patent bypass and
      durable repair. CONCLUSION: Renal artery stent infection with pseudoaneurysm is
      rare and can be diagnosed with duplex ultrasound. Renal salvage can be obtained
      but requires stent removal and autologous bypass grafting.

PMID- 19748221
TI  - Endovascular treatment of a ruptured iliac aneurysm previously excluded.
AB  - We report a case of an isolated ruptured iliac artery aneurysm that had
      previously been treated, 25 months before, with iliac endovascular exclusion.
      Urgent computed tomographic (CT) scan showed the retroperitoneal hematoma and a
      type IA endoleak. On an emergency basis, at the operating room, an aortouni-iliac
      graft and femorofemoral crossover bypass were performed, successfully. This is a
      very rare but serious complication and requires careful indication and close
      follow-up with CT. In isolated common iliac artery aneurysms, the common iliac
      artery and distal aorta may tend to enlarge with failure of the endograft
      proximal attachment site and migration, thus leading to a late aneurysm rupture.
      A safe length and width, especially of the proximal sealing zone, should be
      accurately defined and closely followed up, or otherwise complete exclusion of
      the aortoiliac arteries should be considered.

PMID- 19748222
TI  - Factors associated with amputation or graft occlusion one year after lower
      extremity bypass in northern New England.
AB  - BACKGROUND: Optimal patient selection for lower extremity bypass surgery requires
      surgeons to predict which patients will have durable functional outcomes
      following revascularization. Therefore, we examined risk factors that predict
      amputation or graft occlusion within the first year following lower extremity
      bypass. METHODS: Using our regional quality-improvement initiative in 11
      hospitals in northern New England, we studied 2,306 lower extremity bypass
      procedures performed in 2,031 patients between January 2003 and December 2007.
      Sixty surgeons contributed to our database, and over 100 demographic and clinical
      variables were abstracted by trained researchers. Cox proportional hazards models
      were used to generate hazard ratios and surrounding 95% confidence intervals
      (CIs) for our combined outcome measure of major amputation (above-knee or below
      knee) or permanent graft occlusion (loss of secondary patency) occurring within
      the first year postoperatively. RESULTS: We found that within our cohort of 2,306
      bypass procedures 17% resulted in an amputation or graft occlusion within 1 year
      of surgery. Of the 143 amputations performed (8% of all limbs undergoing
      bypasses), 17% occurred in the setting of a patent graft. Similarly, of the 277
      graft occlusions (12% of all bypasses), 42% resulted in a major amputation. We
      identified eight preoperative patient characteristics associated with amputation
      or graft occlusion in multivariate analysis: age <50, nonambulatory status
      preoperatively, dialysis dependence, diabetes, critical limb ischemia, need for
      venovenostomy, tarsal target, and living preoperatively in a nursing home. While
      patients with no risk factors had 1-year amputation/occlusion rates that were
      <1%, patients with three or more risk factors had a nearly 30% chance of
      suffering amputation or graft occlusion by 1 year postoperatively. When we
      compared risk-adjusted rates of amputation/occlusion across centers, we found
      that one center in our region performed significantly better than expected
      (observed/expected ratio 0.7, 95% CI 0.6-0.9, p < 0.04). CONCLUSION: Preoperative
      risk factors allow surgeons to predict the risk of amputation or graft occlusion
      following lower extremity bypass and to more precisely inform patients about
      their operative risk and functional outcomes. Additionally, our model facilitates
      comparison of risk-adjusted outcomes across our region. We believe quality
      improvement measures such as these will allow surgeons to identify best practices
      and thereby improve outcomes across centers.

PMID- 19748223
TI  - Aortic aneurysm and orchitis due to Wegener's granulomatosis.
AB  - We present a patient with Wegener's granulomatosis (WG) with involvement of the
      abdominal aorta, testis, peripheral nerve system, and skin. A 51-year-old man
      presented at our outpatient clinic with lower back pain. He had a history of
      smoking, hypertension, and an embryonal carcinoma of the left testis, treated 13
      years ago with orchidectomy and chemotherapy. One month earlier, he underwent a
      partial orchidectomy of the right testis due to testicular swelling. Abdominal
      computed tomography showed a 3.8 cm wide aneurysm of the distal part of the aorta
      with inflammation. One week later he was admitted to the hospital with numbness
      of his hands and feet. Physical examination showed signs of peripheral
      microemboli. Serological laboratory tests revealed elevated antineutrophil
      cytoplasmic antibody titers with positive reactions against proteinase-3,
      indicating Wegener's disease. The chest X-ray was normal. Pathological
      examination of the right testis showed necrotizing vasculitis of a small artery.
      He was treated with cyclophosphamide and prednisolone. WG with extrapulmonary
      involvement occurs infrequently, and reports of manifestations of WG in aorta,
      testis, the peripheral nerve system, and skin are even more uncommon. Small- and
      medium-vessel vasculitis can precede large-vessel vasculitis or occur in the
      absence of small-vessel involvement. Therefore, WG should be included in the work
      up of large-vessel vasculitis, which can give rise to periaortic inflammation.

PMID- 19748224
TI  - In the absence of distal runoff, open thromboendarterectomy can save the limb in
      patients with prolonged lower limb ischemia due to popliteal artery occlusion.

PMID- 19748225
TI  - Memory in linear recurrent neural networks in continuous time.
AB  - Reservoir Computing is a novel technique which employs recurrent neural networks
      while circumventing difficult training algorithms. A very recent trend in
      Reservoir Computing is the use of real physical dynamical systems as
      implementation platforms, rather than the customary digital emulations. Physical
      systems operate in continuous time, creating a fundamental difference with the
      classic discrete time definitions of Reservoir Computing. The specific goal of
      this paper is to study the memory properties of such systems, where we will limit
      ourselves to linear dynamics. We develop an analytical model which allows the
      calculation of the memory function for continuous time linear dynamical systems,
      which can be considered as networks of linear leaky integrator neurons. We then
      use this model to research memory properties for different types of reservoir. We
      start with random connection matrices with a shifted eigenvalue spectrum, which
      perform very poorly. Next, we transform two specific reservoir types, which are
      known to give good performance in discrete time, to the continuous time domain.
      Reservoirs based on uniform spreading of connection matrix eigenvalues on the
      unit disk in discrete time give much better memory properties than reservoirs
      with random connection matrices, where reservoirs based on orthogonal connection
      matrices in discrete time are very robust against noise and their memory
      properties can be tuned. The overall results found in this work yield important
      insights into how to design networks for continuous time.

PMID- 19748226
TI  - Prevalence of acute repetitive seizures (ARS) in the United Kingdom.
AB  - INTRODUCTION: "Acute repetitive seizures" (ARS) is a term to describe a condition
      manifest by multiple seizures occurring over a relatively brief period of time 
      generally 24 hours- in patients with epilepsy. There is limited information
      regarding the epidemiology of ARS in the general population. METHODS: We
      performed a historical cohort study using data from the United Kingdom General
      Practice Research Database (GPRD) to identify all incident and prevalent cases of
      active epilepsy in 2005. From among this group, we identified individuals at risk
      for ARS. This included those with "catastrophic epilepsy syndromes of childhood"
      (CE), and those with a history of seizure clustering in the context of other
      epilepsy syndromes. RESULTS: We identified 21,010 people with active epilepsy in
      the GPRD in 2005; prevalence 7.2/1000; age adjusted to the European Standard
      Population, 6.7; incidence 50/100,000 per year, age-adjusted 48/100,000. We
      identified 665 people at risk for ARS. The prevalence of CE in the general
      population was 1.2/10,000 and that of cluster seizures was 1.1/10,000. We
      estimated the crude prevalence of ARS in the general population to be 2.3/10,000;
      age adjusted 2.5 (CI, 2.3-2.7. The prevalence of ARS was highest in those 0-4
      years of age (5.9/10,000) and fell with advancing age to 0.5/10,000 in those age
      70 and older). CONCLUSIONS: This is the first population-based study to provide
      information on the prevalence of ARS. ARS affects about 3% of the population with
      epilepsy and 0.02% of the general population. More studies are needed to further
      evaluate this serious epilepsy phenomenon.

PMID- 19748227
TI  - The localizing value of hypersalivation and postictal coughing in temporal lobe
      epilepsy.
AB  - Analysis of ictal semiology is essential to presurgical evaluation of epilepsy
      patients providing information on seizure origin. To assess the significance of
      hypersalivation and postictal coughing for seizure origin in temporal lobe
      epilepsy (TLE), we analyzed video/EEG monitoring documented seizures of 107 adult
      patients for these seizure elements with respect to frequency and sequence of
      occurrence in relation to epileptogenic origin, comparing mesial versus extra
      mesial and left versus right. Hypersalivation was rare, but occurred exclusively
      in seizures of mesial origin (9.4%). Comparison between left (11.4%) and right
      (6.9%) mesial origin was statistically insignificant. Postictal coughing also
      occurred exclusively in seizures of mesial onset (6.3%). Again, comparison
      between left (5.7%) and right (6.9%) mesial seizure onset was statistically
      insignificant. Thus, hypersalivation and postictal coughing are rare seizure
      phenomena in TLE, but their occurrence strongly support mesial seizure origin.

PMID- 19748228
TI  - Striatal metabolic alterations in non-psychotic adolescent offspring at risk for
      schizophrenia: a (1)H spectroscopy study.
AB  - In vivo proton ((1)H) Magnetic Resonance spectroscopy ((1)H MRS) has shown
      abnormalities in young first-episode patients with schizophrenia. It is unclear
      whether these abnormalities reflect trait related vs. state related alterations
      in schizophrenia. We compared young first-degree relatives of schizophrenia
      patients and healthy controls using (1)H MRS. We hypothesized alterations in the
      (1)H MRS metabolites N-acetyl aspartate (NAA) and glutamate in corticostriatal
      and thalamic brain regions. We obtained multi-voxel, short-TE (1)H MRS
      measurements at 1.5 Tesla in 40 consenting adolescent offspring at risk for
      schizophrenia (HR), and 48 age matched healthy controls (HC). Absolute levels of
      NAA, phosphocreatine plus creatine (PCr+Cr), choline-containing compounds
      (GPC+PC), myo-inositol and glutamate plus glutamine (Glu+Gln) were obtained from
      the seven different anatomical brain areas (nominal voxel size of 4.5cm(3) each)
      and corrected for tissue voxel composition. HR subjects showed NAA (p=.0049),
      PCr+Cr (p=0.028) and GPC+PC (p=0.0086) reductions in the caudate compared with HC
      subjects. Male HR subjects had significant Glu+Gln reductions compared to male HC
      subjects (p=.0022). HR subjects had increased NAA in prefrontal white matter. NAA
      levels in the prefrontal white matter and Glu+Gln levels in the inferior
      parietal/occipital region were both increased in HR without psychopathology
      compared with HC subjects. Lower NAA, PCr+Cr and GPC+PC levels may reflect an
      overall reduction in cellular processes in the caudate of HC subjects, perhaps
      related to decreases in cell density, or synaptic overpruning. Further studies
      are needed to examine the pathophysiologic significance of these observations,
      and their potential predictive value for schizophrenia related psychopathology
      that may emerge in these at risk relatives during adolescence and early
      adulthood.

PMID- 19748229
TI  - Novel immune response to gluten in individuals with schizophrenia.
AB  - A link between celiac disease and schizophrenia has been postulated for several
      years, based primarily on reports of elevated levels of antibody to gliadin in
      patients. We sought to examine the proposed connection between schizophrenia and
      celiac disease by characterizing the molecular specificity and mechanism of the
      anti-gliadin immune response in a subset of individuals with schizophrenia. Blood
      samples from individuals with schizophrenia and elevated anti-gliadin antibody
      titer were examined for celiac disease-associated biomarkers, including
      antibodies to transglutaminase 2 (TG2) enzyme and deamidated gliadin peptides, as
      well as the HLA-DQ2 and -DQ8 MHC genes. The anti-gliadin antibody response was
      further characterized through examination of reactivity towards
      chromatographically separated gluten proteins. Target proteins of interest were
      identified by peptide mass mapping. In contrast to celiac disease patients, an
      association between the anti-gliadin immune response and anti-TG2 antibody or HLA
      DQ2 and -DQ8 markers was not found in individuals with schizophrenia. In
      addition, the majority of individuals with schizophrenia and anti-gliadin
      antibody did not exhibit antibody reactivity to deamidated gliadin peptides.
      Further characterization of the antibody specificity revealed preferential
      reactivity towards different gluten proteins in the schizophrenia and celiac
      disease groups. These findings indicate that the anti-gliadin immune response in
      schizophrenia has a different antigenic specificity from that in celiac disease
      and is independent of the action of transglutaminase enzyme and HLA-DQ2/DQ8.
      Meanwhile, the presence of elevated levels of antibodies to specific gluten
      proteins points to shared immunologic abnormalities in a subset of schizophrenia
      patients. Further characterization and understanding of the immune response to
      gluten in schizophrenia may provide novel insights into the etiopathogenesis of
      specific disease phenotypes.

PMID- 19748230
TI  - Candida albicans isolates from APECED patients show decreased susceptibility to
      miconazole.

PMID- 19748231
TI  - Correlation between meropenem and doripenem use density and the incidence of
      carbapenem-resistant Pseudomonas aeruginosa.
AB  - Optimal use of carbapenems is an important issue in the prevention of resistance
      in Pseudomonas aeruginosa. In this study, we investigated the correlation between
      antimicrobial use density (AUD) of carbapenems and imipenem/cilastatin (IPM/CS)
      or meropenem (MEPM) susceptibility of P. aeruginosa strains. The AUD of five
      carbapenems [IPM/CS, panipenem/betamipron, biapenem, MEPM and doripenem (DRPM)]
      was examined every 6 months between 2006 and 2008. The AUD was calculated using
      the defined daily doses methodology developed by the World Health Organisation. A
      minimum inhibitory concentration of IPM/CS or MEPM of < or =4 mg/L was considered
      to be sensitive. There was a significant negative correlation between MEPM
      susceptibility and the total AUD of MEPM and DRPM [r=-0.823, 95% confidence
      interval (CI) -0.035 to -0.980; P=0.044]. Furthermore, there was a significant
      correlation between MEPM susceptibility and IPM/CS susceptibility (r=0.839, 95%
      CI 0.084 to 0.981; P=0.037). Cross-resistance was therefore investigated and only
      5.6% of MEPM-insensitive strains were susceptible to IPM/CS, although 43.3% of
      IPM/CS-insensitive strains were susceptible to MEPM. These results suggest that
      curtailing the use of MEPM and DRPM may curb the emergence not only of MEPM
      resistant strains but also IPM/CS-resistant strains.

PMID- 19748232
TI  - Prevalence and types of extended-spectrum beta-lactamases among urinary
      Escherichia coli and Klebsiella spp. in New Zealand.
AB  - The aims of this survey were (i) to determine the prevalence of extended-spectrum
      beta-lactamases (ESBLs) among urinary Escherichia coli and Klebsiella spp. in New
      Zealand (NZ), (ii) to identify the relative prevalence of ESBL types and (iii) to
      investigate clonality among ESBL-producing E. coli and Klebsiella spp. During a 4
      week period in 2006, 86% of NZ hospital and community diagnostic microbiology
      laboratories participated in the survey and referred isolates to the national
      reference laboratory. A total of 86 ESBL-producing isolates were identified,
      comprising 55 E. coli and 31 Klebsiella spp. (all Klebsiella pneumoniae),
      equating to prevalence rates of 0.7% and 4.2%, respectively. The majority of the
      ESBL-producing E. coli (80.0%) and K. pneumoniae (58.6%) were reported to be from
      community-acquired urinary tract infections. CTX-M-15 and CTX-M-14 accounted for
      75.9% and 13.3%, respectively, of the ESBL types identified. A novel ESBL,
      designated CTX-M-68, was identified. Most CTX-M-15-producing isolates were
      multiresistant to three or more antibiotic classes. Pulsed-field gel
      electrophoresis typing identified a wide diversity of strains among the ESBL
      producing E. coli, whereas the K. pneumoniae were more clonal. The results of
      this survey show that the prevalence of ESBLs has increased in recent years in
      NZ, that CTX-M ESBLs are almost wholly dominant and that ESBL-producing organisms
      are already established as community-acquired pathogens.

PMID- 19748233
TI  - A study of the antimicrobial activity of selected synthetic and naturally
      occurring quinolines.
AB  - The antimicrobial activities of 60 naturally occurring and synthetic quinolines
      were studied. The quinolines were organised into seven structural subgroups and,
      using an in-house microtitre assay, were tested against a range of gram-positive
      and gram-negative bacteria, including a hospital isolate of meticillin-resistant
      Staphylococcus aureus (MRSA). The quinolines exhibiting good bioactivity [i.e.
      low minimum inhibitory concentration (MIC)] against two S. aureus strains were
      then assessed for their antimicrobial activity against a range of eight
      clinically isolated MRSA strains. The study showed that 30 of the tested
      compounds displayed antimicrobial activity, mostly against gram-positive
      bacteria. The effects of substituent groups on the bioactivity of these
      quinolines have also been discussed. The quinoline 4-hydroxy-3-iodo-quinol-2-one
      (11) exhibited significant antimicrobial activity, being active against the MRSA
      clinical isolates with MIC values comparable with the antibiotic vancomycin used
      in the treatment of MRSA infections. In particular, 4-hydroxy-3-iodo-quinol-2-one
      (11) showed MIC values of 0.097 microg/mL against an Irish hospital MRSA-1 strain
      and 0.049 microg/mL against a distinct MRSA strain as well as a non-typeable MRSA
      strain.

PMID- 19748234
TI  - In vitro susceptibilities of aerobic and facultative anaerobic Gram-negative
      bacilli from patients with intra-abdominal infections worldwide from 2005-2007:
      results from the SMART study.
AB  - SMART (Study for Monitoring Antimicrobial Resistance Trends) is an ongoing
      multiyear surveillance study to monitor worldwide antimicrobial resistance trends
      among aerobic and facultative anaerobic Gram-negative bacilli (GNB) isolated from
      intra-abdominal infections. During 2005-2007, a total of 255 laboratories from 37
      countries in five global regions collected intra-abdominal GNB for antimicrobial
      susceptibility testing using broth microdilution according to Clinical and
      Laboratory Standards Institute guidelines. A total of 19703 GNB were isolated
      from intra-abdominal infections, comprising 5476, 6633 and 7594 GNB were isolated
      in the years 2005, 2006 and 2007 from 75, 84 and 96 medical centres,
      respectively. The most frequently isolated organisms were Escherichiacoli,
      Klebsiella pneumoniae and Enterobacter cloacae, of which 18.0% of E. coli and
      26.2% of K. pneumoniae were positive for extended-spectrum beta-lactamase (ESBL).
      Overall, resistance among GNB increased during 2005-2007 and resistance rates in
      2007 were generally higher than data from previous years. Ertapenem and imipenem
      were the only agents that maintained consistent activity against GNB, including
      most ESBL-producing isolates.

PMID- 19748235
TI  - Regulation of adult neurogenesis by stress, sleep disruption, exercise and
      inflammation: Implications for depression and antidepressant action.
AB  - Adult hippocampal neurogenesis, a once unorthodox concept, has changed into one
      of the most rapidly growing fields in neuroscience. The present report results
      from the ECNP targeted expert meeting in 2007 during which cellular plasticity
      changes were addressed in the adult brain, focusing on neurogenesis and apoptosis
      in hippocampus and frontal cortex. We discuss recent studies investigating
      factors that regulate neurogenesis with special emphasis on effects of stress,
      sleep disruption, exercise and inflammation, a group of seemingly unrelated
      factors that share at least two unifying properties, namely that they all
      regulate adult hippocampal neurogenesis and have all been implicated in the
      pathophysiology of mood disorders. We conclude that although neurogenesis has
      been implicated in cognitive function and is stimulated by antidepressant drugs,
      its functional impact and contribution to the etiology of depression remains
      unclear. A lasting reduction in neurogenesis following severe or chronic stress
      exposure, either in adult or early life, may represent impaired hippocampal
      plasticity and can contribute to the cognitive symptoms of depression, but is, by
      itself, unlikely to produce the full mood disorder. Normalization of reductions
      in neurogenesis appears at least partly, implicated in antidepressant action.

PMID- 19748236
TI  - J-aggregation of cyanine dyes by self-assembly.
AB  - The importance of highly ordered surfaces, containing adsorptive surface states,
      is discussed for J-aggregation by self-assembly. Such nucleating surfaces are
      nanometer-sized edges and corners of cubic AgBr microcrystals, or surface iodide
      clusters located along edges and corners of AgBr:I microcrystals. Of particular
      interest are dendrimers, monoatomic steps on terraced silver halide microcrystals
      and fullerene derivatives as nucleating surfaces. Molecular organisation into J
      aggregates by self-assembly was realized using aprotic, apolar solvents for
      fullerenes, and polar solvents for dendrimers and monoatomic surface steps. By
      using dendrimers as nucleating agents in mesopores of metal oxide nanoparticle
      coatings, size-controlled and stable J-aggregates with high optical densities and
      strong fluorescence were obtained reproducibly. Such films may be useful for
      sensors, opto-electronics, lighting and photovoltaics.

PMID- 19748237
TI  - Surface free energy and topography of mixed lipid layers on mica.
AB  - The Langmuir-Blodgett/Schaefer (LB/LS) method, AFM technique and contact angle
      measurements were used to investigate the formation, structure and energetic
      properties of lipid films, which were constituted of single-component or binary
      systems formed by phospholipids: saturated 1,2-dipalmitoyl-sn-glycero-3
      phosphocholine (DPPC), unsaturated 1,2-dioleoyl-sn-glycero-3-phosphocholine
      (DOPC) and triglyceride: glyceryl trioleate (GTO) or their mixture DPPC/DOPC and
      DPPC/GTO with a different DOPC or GTO molar ratio. The surface free energy and
      its components (apolar and polar interaction) for single and binary lipid mono-
      and bilayer systems were evaluated from the advancing and receding contact angles
      of water, formamide and diiodomethane, using two different models of interfacial
      interactions, namely, van Oss et al. (LWAB) and the contact angle hysteresis
      (CAH). The molecular structure of these layers was studied by means of atomic
      force microscopy (AFM). The thermodynamic analysis of the excess area and excess
      free energy of DPPC/DOPC mixture indicated that lateral phase separation took
      place for these two components. The AFM images also confirmed the phase
      separation, which was visualized as condensed DPPC-rich domains and a fluid DOPC
      matrix. Saturated DPPC mono- and bilayers exhibited much lower surface free
      energy than unsaturated DOPC ones, probably due to the differences in the packing
      of molecules. In the DPPC/DOPC mixed layers the energy increased with increasing
      mole fraction of DOPC in the layer. For DPPC/GTO layers a similar trend in the
      energy changes as a function of GTO amount was observed. These studies provided a
      fundamental framework for better understanding of the interactions occurring in
      the used lipid systems.

PMID- 19748238
TI  - Physicochemical characterization and biological activity of synthetic TLR4
      agonist formulations.
AB  - Immunostimulatory molecules such as monophosphoryl lipid A (MPL), a Toll-like
      receptor 4 (TLR4) agonist, can be formulated to enhance vaccine adjuvant effects
      and to promote a Th1-type immune response. This study compares the in vitro and
      in vivo potency of aqueous and emulsion formulations containing a synthetic MPL
      analogue. In addition, formulation structure and association of the synthetic TLR
      4 agonist and antigen with the formulation are characterized using dynamic light
      scattering, zeta potential measurement, HPLC, and SDS-PAGE. The biological and
      biophysical effects of formulating the agonist with different oil and surfactant
      components from animal, plant, and synthetic sources are examined. These findings
      have important implications for the formulation of TLR4 agonists as well as the
      influence of formulation component substitution on adjuvant activity. The results
      indicate that (1) the agonist is associated with the oil droplets in emulsion
      formulations, (2) the emulsion formulations containing synthetic TLR4 agonist
      induce higher IgG2a/IgG1 antibody ratios than aqueous formulations or an emulsion
      formulation without the agonist, and (3) appropriate plant-derived components can
      be substituted for animal-derived components in oil-in-water emulsions without
      loss of biological activity.

PMID- 19748239
TI  - Influence of aminoglycoside antibiotics on the thermal behaviour and structural
      features of DPPE-DPPG model membranes.
AB  - The effects of three aminoglycosides (AGs), tobramycin, streptomycin and
      spectinomycin on 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE)-1,2
      dipalmitoyl-sn-glycero-3-[phospho-rac-1-glycerol] (DPPG)/water systems with 0.05
      and 0.2 DPPG/DPPE+DPPG molar fractions were examined by using differential
      scanning calorimetry (DSC), simultaneous small- and wide-angle X-ray scattering
      (SWAXS), and freeze-fracture transmission electronmicroscopy (FF-TE) at 10(-1)
      AG/lipid molar ratio in the doped systems. The effects induced by the AGs
      strongly depend on DPPG/DPPE+DPPG molar fraction. In the presence of the AGs
      regular lyotropic structures form as opposed to the complex and badly correlated
      layer structures of the pure 0.2 DPPG/DPPE+DPPG molar fraction system. The
      investigated AGs possess different structural and thermotropic effects:
      tobramycin and streptomycin which are true aminoglycosides decrease the main
      transition enthalpy in both model systems and induce the formation of correlated
      layer arrangements, while the occurrence of spectinomycin, a non-aminoglycoside
      aminocyclitol still ranked as an AG, results in a hexagonal phase as it can be
      deduced from the SAXS patterns and visually observed in the electronmicrographs.

PMID- 19748241
TI  - Pathophysiology in Japan.

PMID- 19748240
TI  - Lysozyme entrapped within reverse hexagonal mesophases: physical properties and
      structural behavior.
AB  - A model protein (lysozyme) was incorporated into monoolein-based reverse
      hexagonal (H(II)) mesophase and its structure effects were characterized by small
      angle X-ray scattering, ATR-FTIR spectroscopy, and rheological measurements.
      Modifications in molecular organization of the H(II) mesophases as well as the
      conformational stability of lysozyme (LSZ) as a function of pH and denaturating
      agent (urea) were clarified. Up to 3 wt.% LSZ can be solubilized into the H(II).
      The vibration FTIR analysis revealed that LSZ interacted with OH groups of
      glycerol monooleate (GMO) in the outer interface region, resulting in strong
      hydrogen bonding between the surfactant and its environment. Simultaneously, the
      decrease in the hydrogen-bonded carbonyl population of GMO was monitored,
      indicating dehydration of the monoolein carbonyls. These molecular interactions
      yielded a minor decrease in the lattice parameter of the systems, as detected by
      small angle X-ray scattering. Furthermore, LSZ was crystallized within the medium
      of the hexagonal structures in a single crystal form. The alpha-helix
      conformation of lysozyme was stabilized at high pH conditions, demonstrating
      greater helical structure content, compared to D(2)O solution. Moreover, the
      hexagonal phase decreased the unfavorable alpha-->beta transition in lysozyme,
      thereby increasing the stability of the protein under chemical denaturation. The
      rheological behavior of the hexagonal structures varied with the incorporation of
      LSZ, reflected in stronger elastic properties and pronounced solid-like response
      of the systems. The hydrogen bonding enhancement in the interface region of the
      structures was most likely responsible for these phenomena. The results of this
      study provided valuable information on the use of hexagonal systems as a carrier
      for incorporation and stabilization of proteins for various applications.

PMID- 19748242
TI  - [Limp in a 10-year-old boy].

PMID- 19748243
TI  - [Benign sacrococcygeal teratoma in a child: a case report with a review of the
      literature].
AB  - Sacrococcygeal teratomas are rare congenital tumors, generally discovered at
      birth. These tumors are seldom observed in children. Radical resection must be
      performed to avoid potentially malignant recurrence even if the primary lesion is
      benign. We report a case in an 8-year-old girl who did not have a past medical
      history. Since the age of 2 years, she presented a progressive sacral tumefaction
      with no neurological deficit. The MRI showed a large sacrococcygeal cyst in
      hypointense-signal T1-weighted imaging with no contrast enhancement, and a
      hyperintense signal in T2-weighted imaging. At surgery, the tumor was totally
      removed. The intraoperative aspect was that of a viscous cyst. The histological
      study showed a sacrococcygeal teratoma.

PMID- 19748244
TI  - [Consequences of exclusive breast-feeding in vegan mother newborn--case report].
AB  - We report on the case of an infant who was hospitalized because of failure to
      thrive, megaloblastic anemia, and delayed psychomotor development. He was 10
      months old and had been exclusively breast-fed by his vegan mother.
      Investigations showed vitamin B(12) deficiency with hematocytopenia and pervasive
      developmental disorders as well as vitamin K and vitamin D deficiencies. The
      infant's mother presented the same deficiencies. Introduction of vitamin
      supplementation normalized the biological disorders, and the infant showed weight
      gain and neurological improvement. This case highlights that a vegan diet during
      pregnancy followed by exclusive breast-feeding can induce nutritional
      deficiencies in the newborn, with clinical consequences. Detecting mother and
      child vitamin deficiencies and preventing them is essential.

PMID- 19748245
TI  - Dietary patterns and markers for the metabolic syndrome in Australian
      adolescents.
AB  - BACKGROUND AND AIMS: Overweight and other risk factors for cardiovascular disease
      (CVD) as well as their clustering, are increasingly prevalent among adolescents.
      We examined dietary patterns, CVD risk factors, and the clustering of these risk
      factors in 1139 14-year-olds living in Western Australia. METHODS AND RESULTS:
      Usual dietary intake was assessed using a food frequency questionnaire. Two
      dietary patterns, 'Western' and 'Healthy', were identified using factor analysis.
      Associations between these dietary patterns and BMI, waist circumference,
      systolic blood pressure, fasting levels of serum glucose, insulin, total
      cholesterol, HDL-C, LDL-C, triglycerides and insulin resistance were assessed
      using ANOVA. Cluster analysis identified a high risk group (the 'high risk
      metabolic cluster') with features akin to adult metabolic syndrome. Belonging to
      the 'high risk metabolic cluster' was examined in relation to dietary patterns
      using logistic regression, adjusting for aerobic fitness and socio-demographic
      factors. Higher 'Western' dietary pattern scores were associated with greater
      odds for the 'high risk metabolic cluster' (p for trend=0.02) and greater mean
      values for total cholesterol (p for trend=0.03), waist circumference (p for
      trend=0.03) and BMI (p for trend=0.02) in girls, but not boys. Scores for the
      'Healthy' dietary pattern were not related to the 'high risk metabolic cluster'
      but were inversely associated with serum glucose in boys and girls (p for
      trend=0.01 and 0.04, respectively) and were positively associated with HDL-C in
      boys (p for trend=0.02). CONCLUSIONS: Dietary patterns are associated with CVD
      risk factors and the clustering of these risk factors in adolescence.

PMID- 19748246
TI  - Insulin resistance is a risk factor for high blood pressure regardless of body
      size and fat distribution in obese children.
AB  - BACKGROUND AND AIM: The prevalence of children with hypertension is increasing,
      especially in obese children. This study was to assess the relationship between
      blood pressure, indexes of adiposity, body fat distribution and insulin
      resistance. METHODS AND RESULTS:  SAMPLE: 1044 children (M/F: 484/560; aged 6-11
      years). Anthropometry and blood pressure were measured and fasting blood samples
      were tested for triacylglycerol, total cholesterol, HDL cholesterol, glucose,
      insulin and ALT. The prevalence of high blood pressure in overweight males and
      females was 14.3 and 6.4%, respectively (chi(2)=16.73, p<0.001) and in obese it
      was 40.4 and 32.8%, respectively (chi(2)=5.56, p<0.001). High blood pressure
      increased progressively with BMI z-score categories (chi(2)=67.99, p<0.001) as
      well as with waist/height ratio (W/Hr) categories (chi(2)=23.51, p<0.001).
      Hypertensive subject had significantly higher insulin (15.6+/-9.8 vs 11.9+/-7.2,
      p<0.001 and 20.63+/-14.7 vs 15.26+/-9.8, p<0.001 in males and females
      respectively) and HOMA(IR) (3.23+/-2.1 vs 2.42+/-1.49, p<0.001 and 4.12+/-2.87 vs
      3.07+/-1.98, p<0.001 in males and in females, respectively) than non-hypertensive
      ones. Among metabolic and cardiovascular risk factors, HOMA(IR) was the only
      variable able to predict high blood pressure in obese boys and girls, in addition
      to BMI or body fat distribution (waist, W/Hr). The highest HOMA(IR) category was
      the most important predicting factor of high blood pressure in overweight and
      obese children in addition to body size or body fat distribution. CONCLUSIONS:
      Blood pressure is associated with the degree of overweight and the indices of
      body fat distribution. Insulin resistance is an independent additional risk
      factor for hypertension.

PMID- 19748247
TI  - Plant sterols from rapeseed and tall oils: effects on lipids, fat-soluble
      vitamins and plant sterol concentrations.
AB  - BACKGROUND AND AIMS: Data comparing the impact of different sources of plant
      sterols on CVD risk factors and antioxidant levels is scarce. We evaluated the
      effects of plant sterols from rapeseed and tall oils on serum lipids,
      lipoproteins, fat-soluble vitamins and plant sterol concentrations. METHODS AND
      RESULTS: This was a double-blinded, randomized, crossover trial in which 59
      hypercholesterolemic subjects consumed 25 g/day of margarine for 4 weeks
      separated by 1 week washout periods. The two experimental margarines provided
      2g/day of plant sterols from rapeseed or tall oil. The control margarine had no
      added plant sterols. The control margarine reduced LDL cholesterol by 4.5% (95%
      CI 1.4, 7.6%). The tall and rapeseed sterol margarines additionally reduced LDL
      cholesterol by 9.0% (95% CI 5.5, 12.4%) and 8.2% (95% CI 5.2, 11.4%) and
      apolipoprotein B by 5.3% (95% CI 1.0, 9.6%) and 6.9% (95% CI 3.6, 10.2%),
      respectively. Lipid-adjusted beta-carotene concentrations were reduced by both
      sterol margarines (P<0.017). alpha-Tocopherol concentrations were reduced by the
      tall sterol compared to the rapeseed sterol margarine (P=0.001). Campesterol
      concentrations increased more markedly with the rapeseed sterol versus tall
      sterol margarine (P<0.001). The rapeseed sterol margarine increased while the
      tall sterol margarine decreased brassicasterol concentrations (P<0.001).
      CONCLUSIONS: Plant sterols from tall and rapeseed oils reduce atherogenic lipids
      and lipoproteins similarly. The rapeseed sterol margarine may have more favorable
      effects on serum alpha-tocopherol concentrations.

PMID- 19748248
TI  - Normal weight obesity: relationship with lipids, glycaemic status, liver enzymes
      and inflammation.
AB  - BACKGROUND AND AIMS: Normal weight obesity (NWO) is defined as an excessive body
      fat associated with a normal body mass index (BMI) and has been associated with
      early inflammation, but its relationship with cardiovascular risk factors await
      investigation. METHODS AND RESULTS: Cross-sectional study including 3213 women
      and 2912 men aged 35-75 years to assess the clinical characteristics of NWO in
      Lausanne, Switzerland. Body fat was assessed by bioimpedance. NWO was defined as
      a BMI<25 kg/m(2) and a % body fat >=66(th) gender-specific percentiles. The
      prevalence of NWO was 5.4% in women and less than 3% in men, so the analysis was
      restricted to women. NWO women had a higher % of body fat than overweight women.
      After adjusting for age, smoking, educational level, physical activity and
      alcohol consumption, NWO women had higher blood pressure and lipid levels and a
      higher prevalence of dyslipidaemia (odds-ratio=1.90 [1.34-2.68]) and fasting
      hyperglycaemia (odds-ratio=1.63 [1.10-2.42]) than lean women, whereas no
      differences were found between NWO and overweight women. Conversely, no
      differences were found between NWO and lean women regarding levels of CRP,
      adiponectin and liver markers (alanine aminotransferase, aspartate
      aminotransferase and gamma glutamyl transferase). Using other definitions of NWO
      led to similar conclusions, albeit some differences were no longer significant.
      CONCLUSION: NWO is almost nonexistent in men. Women with NWO present with higher
      cardiovascular risk factors than lean women, while no differences were found for
      liver or inflammatory markers. Specific screening of NWO might be necessary in
      order to implement cardiovascular prevention.

PMID- 19748249
TI  - Carbohydrate restriction favorably alters lipoprotein metabolism in Emirati
      subjects classified with the metabolic syndrome.
AB  - BACKGROUND AND AIMS: Carbohydrate restriction (CR) has been shown to improve
      dyslipidemias associated with metabolic syndrome (MetS). We evaluated the effects
      of CR on lipoprotein subfractions and apolipoproteins in Emirati adults
      classified with the MetS. METHODS AND RESULTS: 39 subjects (15 men/24 women) were
      randomly allocated to a CR diet [20-25% energy from carbohydrate (CHO)] for 12 wk
      (CRD group) or a combination treatment consisting of CRD for 6 wk followed by the
      American Heart Association diet (50-55% CHO, AHA group) for an additional 6 wk.
      All subjects reduced body weight, LDL cholesterol and triglycerides (P<0.01). At
      baseline all subjects had low concentrations of medium VLDL and total HDL
      particles associated with the very low plasma triglycerides and HDL cholesterol
      in this population. After 12 wk, the large VLDL subfraction was decreased over
      time for subjects in the CRD group (P<0.01) while these changes were not observed
      in those subjects who changed to the AHA diet. The number of medium and small LDL
      particles decreased for all subjects rendering a less atherogenic lipoprotein
      profile. In agreement with these results, a significant decrease in
      apolipoprotein (apo) B was observed (P<0.01). The medium HDL subfraction and apo
      A-II, which can be considered pro-atherogenic, were also decreased over time in
      the CRD group only. CONCLUSIONS: These results suggest that weight loss favorably
      affects lipoprotein metabolism and that the CRD had a better effect on
      atherogenic VLDL and HDL than the low fat diet recommended by AHA.

PMID- 19748250
TI  - Effects of obesity, physical activity, and cardiorespiratory fitness on blood
      pressure, inflammation, and insulin resistance in the National Health and
      Nutrition Survey 1999-2002.
AB  - BACKGROUND AND AIMS: This study was designed to elucidate the effects of obesity,
      self-reported physical activity and cardiorespiratory fitness on blood pressure,
      inflammation, and insulin resistance. METHODS AND RESULTS: Data from 950
      Caucasian subjects ranging in age from 19 to 49 years from the National Health
      and Nutrition Survey (NHANES), 1999-2002, were included to construct a population
      based observational study. Cardiorespiratory fitness (VO(2) max) was predicted
      from a submaximal exercise stress test. Self-reported physical activity was
      measured by metabolic equivalent score transformed from a questionnaire. A
      structural equation model (SEM) was developed to examine the relationship between
      obesity, cardiorespiratory fitness, self-reported physical activity, and
      hypertension, inflammation, and insulin resistance. The model showed that obesity
      was positively linked to hypertension (B=0.50, P<0.001) and C-reactive protein
      (CRP; B=0.15, p<0.05), which in turn led to insulin resistance (B=0.44, P<0.05).
      Increased cardiorespiratory fitness was negatively associated with CRP (Gamma=
      0.23, P<0.01), but not correlated to hypertension after adjustment for potential
      confounding factors. No significant association was found between self-reported
      physical activity and hypertension, insulin resistance, and CRP. CONCLUSION:
      Obesity contributes to the development of hypertension, inflammation, and insulin
      resistance. Improved cardiorespiratory fitness might lead to clinical and
      biochemical improvement in insulin resistance by reducing the inflammatory state.

PMID- 19748251
TI  - Acute effects of 5-methyltetrahydrofolate on endothelial function and asymmetric
      dimethylarginine in patients with chronic heart failure.
AB  - BACKGROUND AND AIMS: Folic acid enhances endothelial function in vascular disease
      states but its effects in chronic heart failure (CHF) are largely unknown. We
      studied the acute effects of i.v. methyltetrahydrofolate (5MTHF), the active
      metabolite of folic acid, on endothelial function and asymmetric dimethylarginine
      (ADMA) in CHF patients. METHODS AND RESULTS: Twenty two CHF patients and 22
      controls received one of the following three-step infusions (1h per each step) in
      a randomized, parallel group, placebo-control study: (1) active treatment
      (saline, 5MTHF, and 5MTHF+the endothelial nitric oxide inhibitor N(G)-monomethyl
      l-arginine, LNMMA); or (2) placebo (salinex3). Endothelium-dependent
      vasodilatation was assessed by pulse-wave analysis (salbutamol-mediated changes
      in augmentation index, AIx). 5MTHF did not exert any significant effects on
      endothelium-dependent vasodilatation both in controls [DeltaAIx post-salbutamol
      baseline -7.6% (-24.8/-4.1) vs. 5MTHF -5.5% (-16.7/-3.6), medians and
      interquartile range, and CHF patients [-1.8% (-17.3/+1.3) vs. -2.4% (-3.8/-1.2)].
      However, a significant reduction in ADMA concentrations was observed in both
      groups [controls baseline 0.68micromol/L (0.64/0.77) vs. 5MTHF 0.65 (0.57/0.74);
      CHF baseline 0.76 (0.63/0.82) vs. 5MTHF 0.69 (0.66/0.71), P=0.05 for both vs.
      baseline and placebo. These effects persisted during co-infusion with LNMMA.
      CONCLUSION: 5MTHF did not affect endothelial function but significantly reduced
      serum ADMA concentrations both in CHF patients and controls. This suggests a
      direct effect of 5MTHF on ADMA metabolism.

PMID- 19748252
TI  - Atherosclerosis regression study in rabbits upon olive pomace polar lipid extract
      administration.
AB  - BACKGROUND AND AIMS: Virgin olive oil polar lipid extract (OOPL) and olive pomace
      polar lipid extract (PPL) have similar antiatherosclerotic effects in cholesterol
      fed rabbits. Our aim was to compare the effect of PPL with that of simvastatin on
      the progression of atherogenesis. METHODS AND RESULTS: Rabbits were fed an
      atherogenic diet for 6 weeks in order to develop dyslipidemia and atheromatous
      lesions. Following documentation of these events in random animals (group A,
      n=6), the remaining were fed for 3 weeks with: standard chow alone (group B,
      n=6), chow supplemented with PPL (group C, n=6), and chow supplemented with
      simvastatin (group D, n=6). Blood was collected at 0, 6 and 9 weeks, to determine
      plasma lipid levels, plasma PAF-AH activity, platelet aggregation (PAF-EC(50)),
      resistance of plasma to oxidation (RPO) and extent of atheromatous lesions in
      aortas. The atherogenic diet induced dyslipidemia and increased PAF-AH activity.
      Dyslipidemia and PAF-activity reduced more effectively in groups C and D. RPO
      decreased in group B only. PAF-EC(50) values decreased in group C only.
      Atherogenesis progression in group C was prevented to an extent indistinguishable
      from that in group D. PAF-AH activity was positively correlated, whereas RPO was
      negatively correlated with the extent of atheromatous lesions. CONCLUSION: PPL,
      as a dietary supplement, is equipotent to simvastatin in preventing the
      progression of atherogenesis.

PMID- 19748253
TI  - Xanthohumol enhances antiviral effect of interferon alpha-2b against bovine viral
      diarrhea virus, a surrogate of hepatitis C virus.
AB  - Xanthohumol (XN) is a natural compound with multifunctional potentials, including
      antiviral activity. In this study, the antiviral activity of addition of XN to
      interferon (IFN)-alpha was examined and compared with each compound alone using
      bovine viral diarrhea virus (BVDV), a surrogate model of hepatitis C virus (HCV).
      BVDV E2 protein and the viral RNA level were determined by immunofluorescence and
      quantitative real-time RT-PCR, respectively. The addition of XN to IFN-alpha
      significantly improved CPEs induced by the virus and inhibited BVDV E2 protein
      and viral RNA levels. The interaction between XN and IFN-alpha was significant
      (P<0.001). XN at 3.13 microg/ml in combination with IFN-alpha at 50 IU/ml showed
      greater inhibitory effect on the viral RNA level than each compound used alone at
      6.25 microg/ml and 100 IU/ml, respectively, indicating synergistic effect on BVDV
      replication in this combination. The inhibitory activity in all the tested
      combinations of XN and IFN-alpha was stronger than that of each compound used
      alone at the corresponding concentration. These results suggest that XN in
      combination with IFN-alpha exhibited a greater in vitro antiviral effect compared
      with each compound used alone. Further studies are deserved to investigate the
      anti-HCV activity of XN and the potential of XN in formulating novel anti-HCV
      regimen.

PMID- 19748254
TI  - Antiprotozoal activity of betulinic acid derivatives.
AB  - Betulinic acid (1), isolated from the crude extract of the leaves of Pentalinon
      andrieuxii (Apocynaceae), together with betulinic acid acetate (2), betulonic
      acid (3), betulinic acid methyl ester (4), and betulin (5) were evaluated for
      their antiprotozoal activity. The results showed that modifying the C-3 position
      increases leishmanicidal activity while modification of the C-3 and C-28
      positions decreases trypanocidal activity.

PMID- 19748255
TI  - Ellagitannins from Tuberaria lignosa as entry inhibitors of HIV.
AB  - Screening of plants from the Iberian Peninsula for anti-human immunodeficiency
      virus (-HIV) activity revealed that aqueous extract of Tuberaria lignosa gave
      positive results. Following an activity-guided procedure, the crude extract was
      counterextracted, and the subsequent fractions obtained tested for their anti-HIV
      activity in vitro. The bioassay-guided fractionation of the extract afforded an
      ellagitannin enriched fraction (EEF) isolated for the first time from this
      species. This EEF exhibited antiviral activity against HIV in MT-2 infected
      cells, with an IC(50) value of 2.33mug/ml (selectivity index greater than 21).
      Inhibition of HIV infection by EEF appears to be mediated by CD4 down-regulation,
      the main receptor for HIV entry. CXCR4 and CCR5 receptors were not affected by
      EEF, explaining why EEF is able to inhibit R5 and X4 infections.

PMID- 19748256
TI  - Anti-inflammatory activity of a HPLC-fingerprinted aqueous infusion of aerial
      part of Bidens tripartita L.
AB  - The anti-inflammatory potential of three doses of an aqueous infusion of aerial
      parts Bidens tripartita L. against carrageenan-induced acute paw edema in rats
      was investigated. A phytochemical study and qualitative-quantitative analyses
      revealed the presence of flavonoids, tannins, polysaccharides, phenols, amino
      acids, ascorbic acid, organic acids and polyacetylenes. Infusion doses of
      20ml/kgbody wt. exhibited significant anti-inflammatory activity in rats, as
      compared with indomethacin. In addition, the infusion showed analgesic properties
      in a hot-plate test and antipyretic properties in carrageenan-induced local
      hyperthermia, both in rats. The effects were dose-dependent. Our results provide
      evidence for the potential usefulness of B. tripartita infusion in the treatment
      of inflammatory disorders.

PMID- 19748257
TI  - WITHDRAWN: Hypoglycemic and hypolipidemic effect of a novel Gymnemic triacetate
      on STZ-induced diabetic rats.
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- 19748258
TI  - Effect of total saponins of "panax notoginseng root" on aortic intimal
      hyperplasia and the expressions of cell cycle protein and extracellular matrix in
      rats.
AB  - AIM OF THE STUDY: the effect of total saponins of "panax notoginseng root" on
      aortic intimal hyperplasia and the expressions of cell cycle protein and
      extracellular matrix in rats MATERIALS AND METHODS: Sprague-Dawley rats were
      randomly divided into sham-operated, control, TSPN and atorvastatin group. Rat
      aorta intima in all groups were injured by insertion of domestic balloon catheter
      into the aortae except sham-operated rats. Drugs were administrated orally from
      the second day after vascular injury and continued for 14 days. The injured
      segments of aortae were collected on the sixteenth day after operation to observe
      the morphological changes of vascular structure and to examine the expressions of
      proliferating cell nuclear antigen(PCNA), cyclinD1, cyclinE, collagen I(Col-I),
      fibronect(FN), matrix metalloproteinase-9(MMP-9) and tissue inhibitor
      metalloproteinase-1(TIMP-1). RESULTS: TPNS significantly inhibited the vascular
      intimal hyperplasia. TPNS significantly lowered the expression of PCNA, cyclinE,
      cyclinD1, FN and MMP-9. TPNS had no significant impacts on the expression of Col
      I and TIMP-1. CONCLUSIONS: Our studies indicated that TSPN could inhibit vessel
      restenosis after vascular intimal injury, and its mechanisms may be related to
      the blockage of the excessive proliferation of VSMC, the reduction of ECM protein
      deposition in the endometrium, and the degradation of ECM protein.

PMID- 19748259
TI  - Diallyl trisulfide induces Bcl-2 and caspase-3-dependent apoptosis via
      downregulation of Akt phosphorylation in human T24 bladder cancer cells.
AB  - It is well known that the garlic-derived organosulfur compounds (OSCs) are
      effective to inhibit a variety of human cancers such as prostate, breast, colon,
      skin, lung, and bladder cancers. Herein, the pro-apoptotic effects of diallyl
      trisulfide (DATS), one of garlic-derived OSCs, on T24 bladder cancer cells were
      investigated. The results demonstrated that DATS suppressed proliferation of T24
      bladder cancer cells in a dose- and time-dependent manner which was associated
      with induced G2/M Phase cell cycle arrest and apoptosis. Mechanistically, DATS
      inhibits phosphatidylinositol 3'-kinase/Akt activation that, in turn, results in
      modulation of Bcl-2 family proteins, leading to enhanced apoptosis of T24 cells.
      These findings suggest that DATS may be an effective way for treating human
      bladder and other types of cancers.

PMID- 19748260
TI  - Impact of chronic obstructive pulmonary disease (COPD) on attention functions.
AB  - The present study investigates the influence of COPD on attention functions,
      learning, and logical thinking. Therefore, 60 COPD patients and 60 healthy
      controls were recruited into a cross-sectional study and underwent extensive
      neuropsychological testing. The Attention Network Test was used for assessment of
      tonic and phasic alertness, orienting, and executive attention. Logical thinking
      and learning were determined with the Standard Progressive Matrices and the
      Verbal and Nonverbal Learning Test, respectively. Significant group differences
      were found in phasic alertness (p=0.001) and orienting (p=0.01) but not in
      executive attention. In addition overall reaction time was significantly slower
      in the COPD group (p=0.001). Further group differences were found in verbal
      (p<0.001) and visual learning (p<0.001) and logical thinking (p<0.001).
      Regression analysis revealed significant correlations for age (p=0.024) and blood
      carbon dioxide levels (p=0.043) in reaction time, a correlation for age and
      orienting (p=0.019) and finally for age (p=0.011) as well as for blood carbon
      dioxide values (p=0.048) and performance in logical thinking. Results are
      indicating a global impairment in cognitive functions of COPD patients which is
      negatively influenced by accelerated aging and increasing with disease severity.

PMID- 19748261
TI  - Immobilization-free multiplex electrochemical DNA and SNP detection.
AB  - A novel electrochemical method for multiplex detection of sequence-specific DNA
      and single nucleotide polymorphism (SNP) that requires no probe immobilization is
      reported. The immobilization-free detection of target DNA is realized by the use
      of a neutrally charged peptide nucleic acid (PNA) probe labeled with an
      electroactive indicator and a negatively charged ITO electrode. Upon
      hybridization between the target DNA and the complementary PNA probe,
      electrostatic repulsion between the negative backbone of the DNA/PNA duplex and
      the negative surface of the ITO electrode prevents the electroactive indicator
      from approaching the electrode, resulting in a significantly suppressed
      electrochemical signal. Multiplex DNA or SNP detection is enabled by using
      multiple PNA probes with different sequences labeled with different
      distinguishable electroactive indicators. Due to the immobilization-free nature
      of this detection scheme, no interference is found between the simultaneous
      detection of multiple target DNAs or SNPs. This simple and robust immobilization
      free multiplex DNA and SNP detection strategy may find applications in a wide
      range of fields especially in point-of-care testing.

PMID- 19748262
TI  - Stage- and area-specific control of stem cells in the developing nervous system.
AB  - The spatiotemporal control of proliferation and differentiation in neural stem
      cells (NSCs) is essential to produce a functional nervous system (NS). Stem cells
      in different areas and at different time points during development have to
      produce different types of cells in a precise manner. Recent studies uncovered a
      plethora of cell extrinsic as well as intrinsic factors that play crucial roles
      in the area-specific and stage-specific control of NSCs. Moreover, recapitulation
      of the spatiotemporal specification of NSCs in vitro opens new avenues for future
      applications. In this review, we have selected some key molecules to discuss the
      mechanisms underlying the spatiotemporal regulation of NSC development.

PMID- 19748263
TI  - Partial characterization of an effluent produced by cooking of Jumbo squid
      (Dosidicus gigas) mantle muscle.
AB  - Jumbo squid (Dosidicus gigas) mantle muscle was cooked simulating industrial
      procedures (95 degrees C x 25 min, 1.2:5 muscle:water ratio). The effluent
      produced was analyzed for chemical and biochemical oxygen demands (COD and
      BOD(5), respectively), proximate analysis, flavor-related compounds (free amino
      acids, nucleotides and carbohydrates) and SDS-PAGE. The COD and BOD(5) exhibited
      variation among samplings (N=3) (27.4-118.5 g O(2)/L for COD and 11.3-26.7 g
      O(2)/L for BOD(5)). The effluent consisted of 1% total solids, 75% of which
      represented crude protein. Sixty percent of the total free amino acid content,
      which imparts flavor in squid species, corresponded to glutamic acid, serine,
      glycine, arginine, alanine, leucine and lysine. The nucleotide concentration
      followed this order, Hx>>ADP>AMP>ATP>IMP>HxR. The variation observed in the
      present work was probably due to physiological maturity differences among the
      squid specimens (i.e., juvenile versus mature). Solids present in squid cooking
      effluent could be recovered and potentially used as flavor ingredients in squid
      analog production by the food industry.

PMID- 19748264
TI  - Composition, phase behavior and thermal stability of natural edible fat from
      rambutan (Nephelium lappaceum L.) seed.
AB  - In this paper, the chemical composition, the main physicochemical properties,
      phase behavior and thermal stability of rambutan (Nephelium lappaceum L.) seed
      fat were studied. These results showed that the almond-like decorticated seed
      represents 6.1% of the wet weight fruit and is: 1.22% ash, 7.80% protein, 11.6%
      crude fiber, 46% carbohydrates, and 33.4% fat (d.b.). The main fatty acids in the
      drupe fat were 40.3% oleic, 34.5% arachidic, 6.1% palmitic, 7.1% stearic, 6.3%
      gondoic, and 2.9% behenic; the refraction, saponification and iodine values were
      1.468, 186, and 47.0, respectively. The phase behavior analysis showed relatively
      simple crystallization and melting profiles: crystallization showed three well
      differentiated groups of triglycerides around maximum peaks at +30.8, +15.6 and 
      18.1 degrees C; the fat-melting curve had a range between -14.5 and +51.8 degrees
      C with a fusion enthalpy of 124.3 J/g. The thermal stability analyzed in an inert
      atmosphere of N(2) and in a normal oxidizing atmosphere, showed that in the
      latter, fat decomposition begins at 237.3 degrees C and concludes at 529 degrees
      C, with three stages of decomposition. According to these results, rambutan seed
      fat has physicochemical and thermal characteristics that may become interesting
      for specific applications in several segments of the food industry.

PMID- 19748265
TI  - Selection of indicator bacteria based on screening of 16S rDNA metagenomic
      library from a two-stage anoxic-oxic bioreactor system degrading azo dyes.
AB  - Dye degradation has gained attention of late due to indiscriminate disposal from
      user industries. Enhancing efficiency of biological treatment provides a cheaper
      alternative vis-a-vis other advanced technologies. Dye molecules are metabolized
      biologically via anoxic and oxic treatments. In this study, bacterial community
      surviving on dye effluent working in anoxic-oxic bioreactor was analyzed using
      16S rDNA approach. Azo-dye decolorizing and degrading bacterial community was
      enriched in lab-scale two-stage anoxic-oxic bioreactor. 16S rDNA metagenomic
      libraries of enriched population were constructed, screened and phylogenetically
      analyzed separately. Removal of approximately 35% COD with complete
      decolorization was observed in anoxic bioreactor. Process was carried out by
      uncultured gamma proteobacterium constituting 48% of the total population and 12%
      clones having homology to Klebsiella. Aromatic amines generated during partial
      treatment under anoxic bioreactor were treated by aerobic population having 72%
      unculturable unidentified bacterium and rest of the population consisting of
      Thauera sp., Pseudoxanthomonas sp., Desulfomicrobium sp., Ottowia sp., Acidovorax
      sp., and Bacteriodetes bacterium sp.

PMID- 19748266
TI  - Preparation and characterization of novel composites based on chitosan and
      clinoptilolite with enhanced adsorption properties for Cu2+.
AB  - Novel ionic composites based on chitosan (CS) and clinoptilolite (CPL), a
      widespread natural zeolite, were prepared in this work as microspheres by a
      "tandem" ionic/covalent cross-linking. The mass ratio between CPL and CS was
      varied in the range 1:10-1:2. The ionic gelation of CS was performed with sodium
      tripolyphosphate and epichlorohydrin was used as covalent cross-linker. An abrupt
      increase of the adsorption capacity for Cu(2+) with the increase of the CPL
      content loaded in the composite compared with cross-linked CS was observed, up to
      20 wt.% of CPL. The external stimuli which control the adsorption of Cu(2+) were
      solution pH and temperature. The optimum adsorption pH was 5.0 and the adsorption
      process was well described by the pseudo-second-order kinetics. The maximum
      adsorption capacity of metal ions was observed after the 2nd cycle of adsorption,
      for all composites.

PMID- 19748267
TI  - Continuous electricity generation by a graphite granule baffled air-cathode
      microbial fuel cell.
AB  - A baffled air-cathode microbial fuel cell (BAFMFC) was designed and operated
      under continuous flow. With glucose fed as substrate, an average voltage of 652
      mV was obtained under the external resistance of 1000 Omega (30 degrees C). The
      maximum power density was 15.2 W/m(3) with the chemical oxygen demand (COD)
      removal rate of 88.0%. The overall resistance was 13.7 Omega while ohmic internal
      resistance was 10.8 Omega. Average COD removal rate was 69.7-88.0%, when COD
      loading varied from 4.11 kg COD/(m(3)NACd) to 16.0 kg COD/(m(3)NACd). The liquid
      from corn stover steam explosion process (COD=7160+/-50mg/L) was treated by
      BAFMFC, and the maximum power density was 10.7 W/m(3) with the average COD
      removal rate was 89.1%. The present study indicated BAFMFC can be comparable to
      the traditional anaerobic baffled reactor in COD removal rate for high
      concentration wastewater and have an advantage in energy harvest from wastewater.

PMID- 19748268
TI  - Novel upflow anaerobic solid-state (UASS) reactor.
AB  - The aim of this work was to evaluate the feasibility of a novel upflow anaerobic
      solid-state (UASS) reactor equipped with liquor recirculation. The performance
      characteristics were obtained from a thermophilic UASS reactor (26.5L) operated
      for 68 days with a mixture of maize silage and straw. In order to prevent an
      accumulation of volatile fatty acids, the process liquor was continuously
      recirculated through anaerobic filters. By raising the volatile solids (VS)
      loading rate from 7.1 to 17 g(VS)L(-1)d(-1), the overall methane yield declined
      from 384 to 312 kg(VS)(-1), while the yield contribution of the anaerobic filters
      increased from 12% to 70%. The chemical oxygen demand (COD) of biodegradable
      particulate matter was removed by 86-93% with a maximum hydrolysis rate of 16.4
      g(COD)L(-1)d(-1). Based on the results, we conclude that the UASS reactor is a
      promising solution for the digestion of various organic materials.

PMID- 19748269
TI  - Phosphoinositide-3-kinase (PI3K) inhibitors: identification of new scaffolds
      using virtual screening.
AB  - In the present work, we used virtual screening (VS) of the ZINC database of 2.5
      million compounds to seek new PI3K inhibitory scaffolds. The VS flowchart
      implemented various filters, including a 3D-database screen, and extensive
      docking studies, to derive 89 derivatives that were experimentally assayed
      against the four PI3K isoforms. Seven compounds showed inhibitory activities
      between 1 and 100 microM, with four being sufficiently potent to constitute
      potential new scaffolds. The binding conformations of these four were analyzed to
      provide a rationalization of their activity profile.

PMID- 19748270
TI  - Plasmodesmata - bridging the gap between neighboring plant cells.
AB  - Land plants have developed highly sophisticated intercellular channels called
      plasmodesmata (PD) that mediate the cell-to-cell trafficking of signaling
      molecules, including non-cell autonomous proteins (NCAPs) and RNAs. Until
      recently, the biological significance of this position-dependent intercellular
      signaling system was underestimated, as only a limited number of endogenous NCAPs
      had been discovered. However, identification of an ever-increasing population of
      NCAPs suggests that the PD communication pathway is involved in diverse
      biological processes, ranging from development to pathogen defense. The
      identification of components involved in plasmodesmal structure and associated
      signaling molecules is now yielding novel insights into the evolution and
      function of PD in mediating the trafficking of non-cell-autonomous information
      macromolecules. Important future challenges are to build a detailed model for the
      plasmodesmal supramolecular complex and to further elucidate the molecular and
      cellular aspects of this novel plant cell-to-cell communication pathway.

PMID- 19748271
TI  - Early biomechanical markers of postural instability in Parkinson's disease.
AB  - Current clinical assessments do not adequately detect the onset of postural
      instability in the early stages of Parkinson's disease (PD). The aim of this
      study was to identify biomechanical variables that are sensitive to the effects
      of early Parkinson's disease on the ability to recovery from a balance
      disturbance. Ten adults diagnosed with idiopathic PD and no clinically detectable
      postural instability, and ten healthy age-range matched controls (HC) completed
      the study. The first step in the response to a backwards waist pull was
      quantified in terms of strategy, temporal, kinematic, kinetic, and center of
      pressure (COP) variables. People with PD, compared to HC, tended to be less
      consistent in the choice of stepping limb, utilized more time for weight shift,
      used a modified ankle joint motion prior to liftoff, and the COP was further
      posterior at landing. The study results demonstrate that PD changes the response
      to a balance disturbance which can be quantified using biomechanical variables
      even before the presence of clinically detectable postural instability. Further
      studies are required to determine if these variables are sensitive and specific
      to postural instability.

PMID- 19748272
TI  - The effect of gait speed on the knee adduction moment depends on waveform summary
      measures.
AB  - The external knee adduction moment (KAM) is a useful proxy for medial knee
      loading. Though many studies examining the KAM report the peak value, recent
      studies have evaluated other measures from this waveform, including the stance
      impulse. It is important to understand the impact of varying gait speed on
      discrete values of the KAM waveform when evaluating differences between samples.
      The purpose of this study was to compare measures of the KAM waveform, including
      peak and impulse, during level walking at different speeds. Thirty-two healthy
      participants (mean age=32+/-8 years, 18 women) were recruited. The KAM peak and
      impulse were calculated over three ambulation speeds: self-selected, slow (15%
      slower than self-selected) and fast (15% faster than self-selected). To identify
      differences between these conditions, a one-way repeated measures analysis of
      variance was utilized. The peak KAM was greater in the fast compared to the slow
      condition (p<0.05). The KAM impulse was greater in the slow compared to both self
      selected and fast conditions (p<0.05). The KAM impulse appeared more sensitive to
      changes in gait speed because the impulse reflects the duration of loading. These
      findings highlight that slowed gait speed increased loading exposure on the
      medial knee tissues, though the maximum magnitude of the exposure was reduced.
      This trade-off between the increase in duration and decrease in amplitude at
      slower gait speeds should be examined, particularly where loading exposure may
      lead to pathology, such as knee osteoarthritis.

PMID- 19748273
TI  - Prevalence of dementia and associated risk factors in Middle Anatolia, Turkey.
AB  - This study aimed to investigate the prevalence of various cognitive disorders in
      the older population (age 55 years and above) of Eskisehir, Turkey, by conducting
      a cluster sampled door-to-door survey. A total of 3100 inhabitants were screened
      with the Mini-Mental State Examination (MMSE) and a questionnaire concerning
      demographic, occupational and social data. Individuals (n=320) with MMSE scores
      of 25 were assessed according to the 10th Revision of the International
      Statistical Classification of Diseases and Related Health Problems (ICD-10) and
      were investigated in the more detailed phase 2 study. The overall prevalence of
      dementia was 8.4%, although it ranged from 2.2% among those aged 55-59 years to
      5.3% among those aged 60-64 years, and to 30.4% among those aged 75 or above.
      Vascular dementia was the most common type (51.1%), followed by Alzheimer's
      dementia (48.8%). In a very small proportion of individuals (0.1%), dementia was
      due to other causes such as B12 deficiency, a tumour or hydrocephalus.
      Significant risk factors for dementia were female sex, low education, age, living
      in a rural area and a family history of dementia.

PMID- 19748274
TI  - Tetraiodobenzimidazoles are potent inhibitors of protein kinase CK2.
AB  - A series of novel iodinated benzimidazoles have been prepared by iodination of
      respective benzimidazole with iodine and periodic acid in sulfuric acid solution.
      Additionally several 2-substituted- and N-1-carboxymethyl-substituted derivatives
      of 4,5,6,7-tetraiodobenzimidazole (TIBI) were obtained. For sake of comparison,
      some new 4,5,6,7-tetrabromobenzimidazoles were also synthesized. The ability of
      the new compounds to inhibit protein kinase CK2 has been evaluated. The results
      show that 4,5,6,7-tetraiodobenzimidazoles are more powerful inhibitors of CK2
      than their tetrabrominated analogs. Molecular modeling supports the experimental
      data showing that tetraiodobenzimidazole moiety fills better the binding pocket
      than respective tetrabromo and tetrachlorocompounds. To note that 4,5,6,7
      tetraiodobenzimidazole (TIBI) is one of the most efficient CK2 inhibitors
      (K(i)=23 nM) described to date.

PMID- 19748275
TI  - Tracheal lacerations after endotracheal intubation: a proposed morphological
      classification to guide non-surgical treatment.
AB  - OBJECTIVE: Postintubation tracheobronchial lacerations (PITLs) are traditionally
      managed surgically. We sought to evaluate the rationale for non-surgical
      management of PITL. METHODS: From January 2003 to November 2008, 30 patients with
      PITL were observed in our institution. PITL were graded as follows: Level I -
      mucosal or submucosal tracheal involvement without mediastinal emphysema and
      without oesophageal injury; Level II - tracheal lesion up to the muscular wall
      with subcutaneous or mediastinal emphysema without oesophageal injury or
      mediastinitis; Level IIIA - complete laceration of the tracheal wall with
      oesophageal or mediastinal soft-tissue hernia without oesophageal injury or
      mediastinitis; Level IIIB - any laceration of the tracheal wall with oesophageal
      injury or mediastinitis. All patients with Level I, II and IIIA PITL were treated
      conservatively with endoscopic instillation of fibrin glue (Tissucol, Baxter
      Healthcare, Deerfield, MA, USA). RESULTS: All patients with Level I (n=3), II
      (n=24) and IIIA (n=2) PITL were successfully treated conservatively. The patient
      with a Level IIIB injury underwent posterolateral thoracotomy repair of the
      trachea. No mortality was reported. Mean hospital stay was 12.9 days. Flexible
      bronchoscopy at 7, 28, 90 and 180 days showed no abnormalities. Complete healing
      was attained in all patients by day 28. CONCLUSIONS: Level I or II PITL should be
      managed non-surgically. When adequate respiratory status is present, Level IIIA
      PITL can be managed conservatively in selected institutions only, because these
      injuries are high-risk injuries. Any PITL associated with injury involving the
      oesophagus or with mediastinitis (Level IIIB) must be treated as soon as possible
      by surgery.

PMID- 19748277
TI  - Pre-emptive local analgesia in video-assisted thoracic surgery sympathectomy.
AB  - OBJECTIVE: Our goal is to determine whether infiltration with a short-acting
      local anaesthetic such as lidocaine before the surgical incision has a pre
      emptive effect on postoperative pain intensity and on incidence of paraesthesia
      in patients undergoing standard thoracoscopic sympathectomy for palmar
      hyperhidrosis. MATERIAL AND METHODS: This prospective study includes a
      consecutive series of 18 patients undergoing bilateral standard thoracoscopic
      sympathectomy for palmar hyperhidrosis during January 2005-December 2007. Each
      patient enrolled in the study was randomised to receive pre-incisional lidocaine
      with epinephrine infiltration of the wounds on the one side, and normal saline
      solution on the other. The identical surgery was performed on each side to allow
      patients to act as their own controls. Then, the side which received local
      analgesia was compared with the control side with regard to pain control and
      paraesthesia after 4, 24 and 168 h postoperatively. The patients and
      investigators were both blinded concerning the side randomised to receive pre
      emptive local analgesia (PLA). RESULTS: We found that patients reported
      significantly less pain on the side treated with pre-emptive local anaesthesia in
      contrast to the control side 4 and 24h after surgery (p=0.001 and p=0.004,
      respectively). However, that difference decreased with time and was no longer
      significant 168 h following surgery (p=0.156). Regarding the paraesthesia, the
      incidence was higher in the control side than the PLA side at 4, 24 and 168 h
      postoperatively, but the difference was not statistically significant. A total of
      17 of 18 (94%) patients noted a change in palmar hyperhidrosis status after
      surgery. CONCLUSION: Our study shows that the pre-injection of local anaesthetic
      before standard thoracoscopic sympathectomy suppresses the local pain mediators,
      hence resulting in significantly less pain in the first postoperative 24 h but
      not thereafter. The clinical impact of the procedure is the possibility of early
      discharge to home and early return to work with potential economical benefits.
      However, because of the small number of patients, further studies are needed to
      corroborate our results.

PMID- 19748278
TI  - Erroneous aortic arch placement of a transvenous pacemaker.

PMID- 19748279
TI  - Extracorporeal membrane oxygenation for refractory cardiogenic shock after
      cardiac surgery: predictors of early mortality and outcome from 51 adult
      patients.
AB  - OBJECTIVE: Extracorporeal membrane oxygenation (ECMO) offers temporary
      haemodynamic support for those with refractory cardiogenic shock after cardiac
      surgery. We review our 5-year experience regarding ECMO use on those who cannot
      be weaned from cardiopulmonary bypass after cardiac surgery. We analyse our
      cases, predict the prognostic factors of survival and compare the short-term and
      medium-term results. METHODS: From January 2002 to December 2006, 1764 patients
      underwent cardiac surgery with cardiopulmonary bypass in our division. Among
      these, 51 patients (2.9%) required venoarterial-mode ECMO for haemodynamic
      support because of refractory postcardiotomy cardiogenic shock. The indication of
      ECMO was refractory cardiogenic shock despite adequate filling volumes, large
      dose inotropes and intra-aortic balloon pump support. The following cardiac
      surgical procedures were performed: coronary artery bypass grafting (CABG), n=27;
      valvular surgery, n=11; CABG plus valvular surgery, n=7; heart transplantation,
      n=4 and other procedures, n=2. RESULTS: Average age was 63.0+/-15.7 years. There
      were 36 male and 15 female patients. Average duration of ECMO was 7.5+/-6.7 days.
      Twenty-seven (53%) patients could be successfully weaned from ECMO. The 30-day
      and 3-month mortalities were 49% (25/51) and 65% (33/51). The in-hospital
      mortality was 67% (34/51 patients). Seventeen (33%) patients could be
      successfully discharged. Fifteen (29%) patients were still alive at 1-year
      outpatient department (OPD) follow-up. CONCLUSIONS: ECMO provides a good
      temporary cardiopulmonary support in patients with postcardiotomy shock. The
      preoperative risk factors of failure to withdraw ECMO are poor left-ventricular
      ejection fraction, systolic blood pressure <90 mmHg and refractory severe
      metabolic acidosis. The peri-ECMO predictors of mortality include low serum
      albumin level, low platelet count, low oxygen pressure of the venous tube of the
      ECMO and poor cardiac systolic function.

PMID- 19748280
TI  - Problem with 'A review of 24 patients with bronchial ruptures: is delay in
      diagnosis more common in children?'.

PMID- 19748281
TI  - Pegfilgrastim primary prophylaxis vs. current practice neutropenia management in
      elderly breast cancer patients receiving chemotherapy.
AB  - We investigated the incidences of febrile neutropenia (FN) and related
      complications in elderly (> or =65 years) breast cancer patients receiving
      chemotherapy supported by pegfilgrastim primary prophylaxis (PP; n=150) or
      current practice (CP) neutropenia management (n=104) in a subanalysis of NeuCuP
      (Neulasta) vs. current practice neutropenia management). Studies involving
      regimens with moderately high to high (> or =15%) FN risk were identified by
      literature review, and individual patient data were integrated for analysis. FN
      incidence was 6% (95% CI: 2, 10%) in the PP group and 24% (95% CI: 16, 32%) in
      the CP group. In cycle 1, incidences were 3 and 15%, respectively. FN-related
      hospitalisation incidence was 5% (PP group) and 15% (CP group), while dose
      reductions (>/=15%) occurred in 15 and 29% of patients. Pegfilgrastim provided
      effective PP in elderly patients, a population who may be vulnerable to
      chemotherapy-related FN and for whom current practice may not provide adequate
      protection.

PMID- 19748282
TI  - Functional implications of genetic variation in human PPARgamma.
AB  - The peroxisome proliferator-activated receptor gamma (PPARgamma) plays a key role
      in the regulation of lipid and glucose metabolism. Human genetic evidence
      supporting this view comes from the study of both common (e.g. the Pro12Ala
      polymorphism) and rare (loss-of-function mutations) variants in the gene encoding
      PPARgamma. Indeed, patients harbouring mutant PPARgamma exhibit familial partial
      lipodystrophy type 3 and an extreme monogenic form of the metabolic syndrome. The
      recent elucidation of the crystal structure of the full-length PPARgamma-RXRalpha
      heterodimer bound to DNA has shed new light on the functional consequences of
      these genetic PPARgamma alterations and provides novel insights as to why
      different perturbations of receptor function unite in a common pathway of
      metabolic dysfunction.

PMID- 19748283
TI  - Bioactive TGF-beta levels can be preserved in plasma samples collected into
      heparin but not EDTA.
AB  - Quantifying TGF-beta is important for many research areas since its effects often
      are dose-dependently bidirectional. The post-transcriptional control of TGF-beta
      bioavailability points out the need to determine TGF-beta at the protein level.
      Studies measuring TGF-beta in peripheral blood have to avoid contamination with
      platelet-derived TGF-beta. Techniques to obtain platelet-poor plasma have been
      suggested, however, the impact of different anti-coagulants on artificial TGF
      beta contamination has not been studied in detail. Here, we compare TGF-beta
      levels in blood samples collected into heparin and EDTA tubes, stored for 0.5-18
      h at various temperatures. We show that contamination with latent TGF-beta can
      only be prevented by collecting the sample on ice. Importantly, levels of
      bioactive TGF-beta in blood collected into heparin but not EDTA tubes remained
      stable up to 18 h, even when kept at RT. Further in vitro experiments indicate
      that heparin prevents the activation of latent TGF-beta into its bioactive form
      probably by virtue of accelerating the complex-formation between AT-III and
      thrombin. Where precise measurement of latent TGF-beta in blood samples is
      required, samples need to be collected on ice; bioactive TGF-beta can be detected
      reliably in samples collected into heparin tubes even when stored at RT.

PMID- 19748284
TI  - What can we learn from ambient ionization techniques?
AB  - Ambient mass spectrometry-mass spectrometric analysis with no or minimal effort
      for sample preparation-has experienced a very rapid development during the last 5
      years, with many different methods now available for ionization. Here, we review
      its range of applications, the hurdles encountered for its quantitative use, and
      the proposed mechanisms for ion formation. Clearly, more effort needs to be put
      into investigation of matrix effects, into defining representative sampling of
      heterogeneous materials, and into understanding and controlling the underlying
      ionization mechanisms. Finally, we propose a concept to reduce the number of
      different acronyms describing very similar embodiments of ambient mass
      spectrometry.

PMID- 19748285
TI  - Complementary peptide sequence coverage using alternative enzymes for on-line
      digestion with a triaxial electrospray probe.
AB  - Using alternative enzymes for on-line digestion with a triaxial electrospray
      probe extends sequence coverage. This is the first report of utilization of our
      triaxial probe for on-line analysis with enzymes other than pepsin, suggesting
      potential for broader application. The probe allows access to processes occurring
      on a timescale and/or involving substrate conformations complementary to those
      for conventional (off-line) digestion. Some of the features observed in
      application to Abeta fibrils are suggestive of unique reactive intermediates
      during dissolution. Data obtained with enzyme mixtures suggest synergistic
      effects.

PMID- 19748286
TI  - Investigation of glycemia recovery with oral administration of glycerol,
      pyruvate, and L-lactate during long-term, insulin-induced hypoglycemia.
AB  - AIM: The acute effect of oral administration of isolated or combined glycerol,
      pyruvate, and L-lactate on glycemia recovery (GR) during long-term, insulin
      induced hypoglycemia (IIH) was compared. METHODS: Glycemia of 24 h-fasted rats
      that received intraperitoneal injection (1.0 U/kg) of regular insulin (IIH group)
      or saline (COG group) and, 15, 150, or 165 min later, oral saline (control IIH),
      glycerol (100 mg/kg), pyruvate (100 mg/kg), L-lactate (100 mg/kg), or combined
      glycerol+pyruvate+L-lactate (each 33.3 or 100 mg/kg) was compared. In addition,
      for comparative purposes, a group that received glucose (100 mg/kg) was included.
      Glycemia was measured 180 min after insulin or saline injection. To investigate
      the participation of the hepatic availability of gluconeogenic substrates to GR,
      livers from IIH and COG rats that received physiological or supraphysiological
      concentrations of isolated or combined glycerol, pyruvate, and L-lactate were
      compared. Liver experiments were done 180 min after insulin or saline injection.
      RESULTS: Oral glycerol, pyruvate, and L-lactate (isolated or combined) or glucose
      promoted GR. Moreover, the best GR was obtained with combined glycerol+pyruvate+L
      lactate (100 mg/kg). In agreement, livers that received supraphysiological
      concentrations of glycerol, pyruvate, and L-lactate (isolated or combined) showed
      higher glucose release than livers that received physiological concentrations of
      these substances (isolated or combined). CONCLUSION: The best GR obtained with
      combined administration of glycerol, pyruvate, and L-lactate (100 mg/kg) during
      long-term IIH was a consequence of the higher liver availability of these
      substances associated with a maintained liver ability to produce glucose from
      gluconeogenic substrates.

PMID- 19748287
TI  - Aldose reductase inhibitors in the treatment of diabetic peripheral neuropathy: a
      review.
AB  - PURPOSE: The purpose of this article was to examine how aldose reductase (AR)
      inhibitors are used in the prevention and treatment of peripheral neuropathy in
      diabetes, specifically focusing on efficacy. METHODS: Medline searches were used
      to identify clinical trials investigating AR inhibitors and their proposed
      mechanism of action, efficacy, and adverse effects. Additionally, the references
      of the articles returned by the Medline search were examined for pertinent
      publications. RESULTS: Three AR inhibitors were selected for review. Modest
      improvements in the preservation and restoration of nerve conduction velocities
      were reported in the studies. Additionally, patients reported improvements in the
      subjective symptoms associated with diabetic peripheral neuropathy. Adverse
      effects for the studied agents were minimal or not reported. CONCLUSIONS: Given
      the mechanism by which diabetic peripheral neuropathy can result, targeting the
      polyol pathway as a method of treatment appears promising, yet the efficacy of
      newer AR inhibitors is still to be proven. Currently, these agents are not
      marketed in the United States. As newer studies emerge, diabetes educators will
      learn more about their efficacy and safety in preventing and treating diabetic
      peripheral neuropathy.

PMID- 19748288
TI  - Patients' concepts and attitudes about diabetes.
AB  - OBJECTIVE: To evaluate the concepts and attitudes of patients and their immediate
      family members towards diabetes, its complications, and treatment. RESEARCH
      DESIGN AND METHODS: A total of 654 patients with poorly controlled diabetes and
      216 of their immediate family members were interviewed regarding their concept
      about diabetes, its complications, diet, exercise, drug therapy, and
      understanding about insulin. RESULTS: There was lack of awareness about diabetes
      and its complications among the patients of diabetes. Majority of obese patients
      and their close family members failed to accept that they were obese. Child
      birth, menopause, and tubal ligation in female patients were wrongly attributed
      as a cause of obesity. There were major misconceptions about diet, exercise, and
      insulin therapy. More than 90% of study subjects had a misconception that all
      sweet fruits are prohibited and all bitter vegetables are beneficial. Temporary
      discontinuation of drug therapy was found in 189 cases. The lack of awareness and
      various misconceptions had no statistical relationship with the educational
      background of the patients. CONCLUSION: Among patients of poorly controlled
      diabetes and their close family members, there was a gross lack of knowledge of
      complications of diabetes, causes of obesity, treatment of diabetes, and use of
      insulin. Denial of obesity was commonly observed. Linking obesity with tubal
      ligation in female patients not only is appalling but may possibly be a hindrance
      to family planning program. Level of education had no bearing on these
      misconceptions.

PMID- 19748289
TI  - Anterior midline nodule of the hard palate.

PMID- 19748290
TI  - Internal morphology of ameloblastomas: a study of 24 resected specimens.
AB  - OBJECTIVES: The objectives of this study were to describe the internal
      macroscopic architecture of resected specimens of ameloblastoma and to correlate
      the findings with radiographs and microscopic features. STUDY DESIGN: Resection
      specimens of 24 ameloblastomas were retrieved from the files of the Department of
      Oral Pathology at the University of Limpopo. The neoplasms were sectioned in
      parallel slices and the macroscopic features recorded and each slice was
      radiographed and sampled for microscopic examination. The macroscopic features
      were correlated with respective microscopic and radiological appearances.
      RESULTS: Twenty-three ameloblastomas affected the mandible and 1 the maxilla and
      measured between 3.3 and 20 cm in greatest diameter. Six cases were unicystic, 2
      of which showed incomplete septae both of which presented multilocular on
      radiographs. Intracystic proliferations were present in 15 cases. These
      proliferations showed macroscopic features of either small or large nodules with
      or without the formation of confluent plaques, focal papillary lesions, or
      multinodular masses that protruded into the cystic cavities. Microscopically
      these proliferations were characterized by foci of inflammation or plexiform or
      solid epithelial proliferations, one of which showed a focus of carcinoma in
      situ, adenomatoid differentiation and another osteodentin deposits. Seven cases
      had foci of stromal desmoplastic change, one of which exhibited mineralized
      deposits resembling bone. CONCLUSIONS: The assessment of the cystic nature of
      ameloblastomas on 2-dimensional radiographs is inaccurate. Intraluminal
      proliferations, in situ carcinomatous change, adenoid differentiation, stromal
      osteodentin, and bone deposits and desmoplasia were found to be focal rather than
      generalized phenomena in resection specimen of ameloblastoma.

PMID- 19748291
TI  - Nucleolar organizer regions (AgNOR) and subepithelial vascularization as field
      cancerization markers in oral mucosa biopsies of alcoholic and smoking patients.
AB  - OBJECTIVE: The aim of this study was to show that variations in nucleolar
      organizer regions (AgNOR) and the increase in subepithelial vascularization could
      reveal changes related to markers of field cancerization in alcoholic and smoking
      patients who have not yet expressed clinical or histological malignant lesions.
      STUDY DESIGN: Quantitative variations in epithelial AgNOR and in the
      vascularization of the underlying connective tissue were assessed by image
      analysis in histologically normal biopsy specimens from alcohol drinkers and
      smoking patients (DS). AgNORs were evidenced by silver staining and vessel walls
      were labeled by immunohistochemical demonstration of the CD34 antigen. Samples of
      oral mucosa of nonalcoholic, nonsmoking patients (NDS) obtained during surgical
      procedures served as controls. Eight parameters related to number, volume, and
      shape of nuclei and AgNORs, and 4 parameters related to number and diameter of
      vascular sections were evaluated. Differences between DS and NDS groups were
      statistically evaluated by means of ANOVA test and posterior Bonferroni
      comparisons. RESULTS: The morphometric analysis revealed more irregular-shaped
      AgNORs in the superficial and suprabasal layers of the oral mucosa of DS
      patients. The suprabasal layers also exhibited a significantly larger number of
      AgNORs. The normal oral mucosa of DS patients exhibited a greater vascular
      density, with predominance of small-caliber blood vessels underlying the basement
      membrane. CONCLUSION: The variations in AgNOR and epithelial vascularization
      would be practical biomarkers to evaluate changes underlying the augmented risk
      of cancerization in oral mucosa.

PMID- 19748292
TI  - The clinical spectrum of Actinomyces-associated lesions of the oral mucosa and
      jawbones: correlations with histomorphometric analysis.
AB  - OBJECTIVES: To characterize the clinical manifestations of Actinomyces-associated
      lesions of the oral mucosa and jawbones, and to correlate the clinical course and
      treatment requirements with the findings of histomorphometric analysis. STUDY
      DESIGN: The study was a 10-year retrospective analysis of archived cases with
      microscopic identification of Actinomyces infection. Actinomyces colonies were
      identified, using hematoxylin-eosin, Gram, and periodic acid-Schiff stains,
      exhibiting filamentous morphology with color variation between center and
      periphery. Only colonies with adjacent tissue reaction (inflammation, fibrosis)
      were analyzed. Actinomyces density (AD) was calculated by dividing total number
      of colonies by tissue surface, Actinomyces relative surface (ARS) was calculated
      by dividing total bacterial surface by tissue surface. RESULTS: The study
      included 106 cases (48 male, 58 female; aged 13-84 years, mean 50.5 years). Cases
      presented a wide clinical spectrum, involving jawbone and/or oral soft tissues.
      Cases included osteomyelitis associated with bisphosphonates, osteoradionecrosis,
      osteomyelitis unrelated to radiation or bisphosphonates, periapical lesions,
      odontogenic cysts, periimplantitis, and lesion mimicking periodontal disease. The
      AD correlated with median length of antibiotic treatment (R = 0.284; P = .028).
      CONCLUSIONS: Because we were able to identify 106 such cases, the results
      indicate that Actinomyces-associated lesions may not be as rare as would be
      expected from the relatively low number of cases in the literature. Actinomyces
      associated lesions presented in a wide spectrum of clinical settings and a
      variety of contributing factors. Quantitative analysis of the number of bacterial
      colonies (representing bacterial load) could help in evaluating the aggressive
      potential of the lesion and help in treatment planning.

PMID- 19748293
TI  - Anesthetic efficacy of inferior alveolar nerve block plus buccal infiltration or
      periodontal ligament injections with articaine in patients with irreversible
      pulpitis in the mandibular first molar.
AB  - OBJECTIVE: We compared the anesthetic efficacy of inferior alveolar nerve block
      (IANB) plus buccal infiltration (BI) and IANB plus periodontal ligament (PDL)
      articaine injections in patients with irreversible pulpitis in the mandibular
      first molar. STUDY DESIGN: Fifty-seven volunteers, patients with irreversible
      pulpitis in the mandibular first molar admitted to the Department of Stomatology,
      Second Affiliated Hospital, Sun Yat-Sen University, randomly received
      conventional IANB, containing 1.7 mL 4% articaine/HCl with 1:100,000 epinephrine,
      plus either BI or PDL injections containing 0.4 mL articaine/HCl with 1:100,000
      epinephrine. The patients recorded the pain of the injections and endodontic
      access on a Heft-Parker visual analog scale (VAS). RESULTS: According to the VAS
      scores, all patients experienced no or mild pain with BI and PDL injections after
      the application of IANB. Anesthetic success occurred in 81.48% for IANB plus BI
      (IANB/BI) compared with 83.33% for IANB plus PDL injection (IANB/PDL injection).
      None of the observed differences between the 2 groups was significant (P > .05).
      CONCLUSION: Both injection combinations resulted in high anesthetic success in
      patients with irreversible pulpitis in the mandibular first molar.

PMID- 19748294
TI  - Effect of pretreatment dexamethasone on postendodontic pain.
AB  - OBJECTIVE: This study evaluates the use of a preoperative single oral dose of
      dexamethasone for the prevention and control of postendodontic pain. STUDY
      DESIGN: Forty-seven patients were randomly assigned to 2 groups: placebo and
      dexamethasone (4 mg). The medications were administered 1 hour before the start
      of endodontic treatment. Postoperative pain was assessed after 4, 12, 24, and 48
      hours. RESULTS: Dexamethasone resulted in a statistically significant reduction
      in postendodontic pain at 4 and 12 hours (P < .05). However, no statistical
      difference (P > .05) was observed at 24 and 48 hours (Mann-Whitney test). The
      placebo group exhibited higher rescue medication intake (P < .05; Student t
      test). No side effects were reported for any of the medications used. CONCLUSION:
      Preoperative single oral dose of dexamethasone substantially reduced
      postendodontic pain. Further studies are needed to evaluate the applicability of
      these findings to other clinical conditions and drug regimens.

PMID- 19748295
TI  - Oral microbial and respiratory status of persons with mental
      retardation/intellectual and developmental disability: an observational cohort
      study.
AB  - OBJECTIVE: The objective of this study was to determine the prevalence of select
      microorganisms in oral biofilms and to investigate relationships between oral and
      respiratory status in persons with mental retardation/intellectual and
      developmental disabilities (IDD). STUDY DESIGN: We conducted a 6-month-long
      observational cohort study with 63 persons with IDD. Oral examinations, oral
      sampling, and medical record reviews were performed at baseline and then monthly.
      Polymerase chain reaction (PCR) was used to analyze all baseline oral samples for
      the presence of Streptococcus pneumoniae, Methicillin-resistant Staphylococcus
      aureus (MRSA), Prevotella melaninogenica, and Candida albicans. PCR analyses were
      also performed on participants' samples collected in the month before being
      diagnosed with a respiratory infection. RESULTS: All subjects had P.
      melaninogenica detected by PCR in their oral samples. Fifty-five percent (35 of
      63) of participants had S. pneumoniae, MRSA, and C. albicans in their oral
      samples at baseline. No dental decay was detected clinically, oral hygiene was
      fair, and dysphagia was common. During the 6 months of the study, there were 22
      respiratory infections (35% of participants)-12 pneumonias, 7 sinusitis, 1
      bronchitis, and 1 upper respiratory tract infection. Participants with
      microorganisms in their baseline samples were significantly more likely to
      develop any respiratory infection and those who had poor oral status were
      significantly more likely to develop pneumonia. Almost 60% of participants who
      developed respiratory infections had the same microorganism detected in the
      sample collected in the month before infection as had been detected in their
      baseline sample. CONCLUSION: Potentially pathogenic microorganisms in the oral
      cavity and poor oral status significantly increased the risk of developing
      respiratory infections, including pneumonia, in persons with IDD. The results
      suggest that colonization with these microorganisms may persist despite routine
      tooth brushing. Meticulous comprehensive oral hygiene of the oral cavity may be
      needed to reduce oropharyngeal microbial load.

PMID- 19748296
TI  - Peripheral ameloblastoma in-situ: an evidential fact of surface epithelium
      origin.
AB  - The proposed origin from the adult gingival epithelium for peripheral
      ameloblastoma is difficult to prove and still remains unresolved. This report
      details a small fibrous polyp on the maxillary edentulous ridge of a 73-year-old
      woman, in which the basal layer of covering squamous epithelium dipped down
      toward the lamina propria over a wide area. Basal cells of the downgrowth were
      ameloblastic in type, and bulbous parts assumed an appearance of the bud-shaped
      enamel organ. Multiple sectioning failed to detect any epithelial nests in the
      submucosa. In addition to the morphologic overlap, early ameloblastoma epithelia
      shared antigenic properties with tumor cells of representative control examples
      of peripheral ameloblastoma. This is the first description of an in situ lesion
      of peripheral ameloblastoma, to our knowledge, and its multifocal ameloblastoma
      changes can be accepted as a direct proof of origin from the surface epithelium.

PMID- 19748297
TI  - Periapical surgery using ultrasonic preparation and thermoplasticized gutta
      percha with AH Plus sealer or IRM as retrograde root-end fillings in 160
      consecutive teeth: a prospective randomized clinical study.
AB  - OBJECTIVE: The aim of this study was to evaluate the healing outcome after
      periapical surgery with an ultrasonic cleaning technique in conjunction with the
      use of either of 2 different retrograde root-filling materials in teeth with
      apical periodontitis. STUDY DESIGN: One hundred sixty teeth in 139 consecutive
      patients were randomly allocated into 2 groups receiving either IRM or
      thermoplasticized gutta-percha (GP) with AH Plus sealer as a retrograde root-end
      seal. The patients were reviewed 12 months after surgery. The results were
      analyzed with Fisher exact test. RESULTS: One hundred forty-seven teeth in 131
      patients were reviewed. Radiologic evaluation and clinical examination showed an
      85% success rate for the IRM group and 90% for GP group. There was no statistical
      significance between the 2 groups. CONCLUSION: Both tested materials, IRM and GP,
      are suitable as retrograde root-end filling materials in conjunction with
      ultrasonic root-end preparation according to the results of the healing outcome
      after 12 months follow-up.

PMID- 19748298
TI  - Evaluating the paper point technique for locating the apical foramen after canal
      preparation.
AB  - OBJECTIVE: Despite not having been formally evaluated in the endodontic
      literature, claims have been made regarding the acceptability of the paper point
      technique (PPT) in estimating the location of the apical foramen (AF). Our aim
      was to investigate the repeatability and accuracy of PPT in estimating AF
      location in a cohort of dental patients. STUDY DESIGN: Root canals with </=10
      degrees of curvature (n = 71) in unsalvageable anterior and premolar teeth were
      measured using PPT as described in the literature. An endodontic file was
      cemented in each canal to the position indicated by PPT. Teeth were extracted and
      microscopic computerized tomography scanned. RESULTS: The PPT was 0.5 mm short to
      0.5 mm long of AF in 87% of the canals. Repeated measurements in a given canal
      were within 0.19 mm of each other 95% of the time. CONCLUSION: For relatively
      straight root canals, PPT appears to be similar to current clinically acceptable
      techniques in estimating AF location.

PMID- 19748299
TI  - Hyperarousal and insomnia.

PMID- 19748300
TI  - Plant conservation genetics in a changing world.
AB  - Plant conservation genetics provides tools to guide conservation and restoration
      efforts, measure and monitor success, and ultimately minimize extinction risk by
      conserving species as dynamic entities capable of evolving in the face of
      changing conditions. We consider the application of these tools to rare and
      common species alike, as ongoing threats that increasingly limit their
      resilience, evolutionary potential and survival. Whereas neutral marker studies
      have contributed much to conservation genetics, we argue for a renewed focus on
      quantitative genetic studies to determine how, or if, species will adapt to
      changing conditions. Because restoration plays an increasingly vital role in
      conservation, we discuss additional genetic considerations and research questions
      that must be actively studied now to effectively inform future actions.

PMID- 19748301
TI  - Mycorrhizas and biomass crops: opportunities for future sustainable development.
AB  - Central to soil health and plant productivity in natural ecosystems are in situ
      soil microbial communities, of which mycorrhizal fungi are an integral component,
      regulating nutrient transfer between plants and the surrounding soil via
      extensive mycelial networks. Such networks are supported by plant-derived carbon
      and are likely to be enhanced under coppiced biomass plantations, a forestry
      practice that has been highlighted recently as a viable means of providing an
      alternative source of energy to fossil fuels, with potentially favourable
      consequences for carbon mitigation. Here, we explore ways in which biomass
      forestry, in conjunction with mycorrhizal fungi, can offer a more holistic
      approach to addressing several topical environmental issues, including 'carbon
      neutral' energy, ecologically sustainable land management and CO(2)
      sequestration.

PMID- 19748302
TI  - One for all: the receptor-associated kinase BAK1.
AB  - The plant receptor kinase BAK1/SERK3 has been identified as a partner of ligand
      binding leucine-rich repeat receptor kinases, in particular the brassinosteroid
      receptor BRI1 and the immune receptor FLS2. BAK1 positively regulates BRI1
      receptor function via physical interaction and transphosphorylation. Since its
      first description in 2001, several independent groups have discovered BAK1/SERK3
      as a component of diverse processes, including brassinosteroid signaling, light
      responses, cell death, and plant innate immunity. Here, we summarize current
      knowledge of the functional repertoire of BAK1 and discuss how its multiple
      functions could be integrated, how receptor complexes are potentially formed and
      how specificity might be determined.

PMID- 19748303
TI  - From automaticity to control in bilinguals.

PMID- 19748304
TI  - A parietal-premotor network for movement intention and motor awareness.
AB  - It is commonly assumed that we are conscious of our movements mainly because we
      can sense ourselves moving as ongoing peripheral information coming from our
      muscles and retina reaches the brain. Recent evidence, however, suggests that,
      contrary to common beliefs, conscious intention to move is independent of
      movement execution per se. We propose that during movement execution it is our
      initial intentions that we are mainly aware of. Furthermore, the experience of
      moving as a conscious act is associated with increased activity in a specific
      brain region: the posterior parietal cortex. We speculate that movement intention
      and awareness are generated and monitored in this region. We put forward a
      general framework of the cognitive and neural processes involved in movement
      intention and motor awareness.

PMID- 19748305
TI  - The emergence of multisensory systems through perceptual narrowing.
AB  - According to conventional wisdom, multisensory development is a progressive
      process that results in the growth and proliferation of perceptual skills. We
      review new findings indicating that a regressive process - perceptual narrowing -
      also contributes in critical ways to perceptual development. These new data
      reveal that young infants are able to integrate non-native faces and
      vocalizations, that this broad multisensory perceptual tuning is present at
      birth, and that this tuning narrows by the end of the first year of life, leaving
      infants with the ability to integrate only socio-ecologically-relevant
      multisensory signals. This narrowing process forces us to reconsider the
      traditional progressive theories of multisensory development and opens up several
      new evolutionary questions as well.

PMID- 19748306
TI  - Recent highlights in systems chemistry.
AB  - Systems chemistry deals with complex systems which exhibit properties that emerge
      only through the collective behavior of its components. Selected examples of
      recent advances in this field include the spontaneous synchronization of
      oscillating reactions, new methodology for developing chemical systems that
      exhibit reaction-diffusion patterns, chiral symmetry breaking in dispersions of
      crystals, the emergence of self-replicators from molecular networks, and self
      assembly under kinetic control.

PMID- 19748307
TI  - Characteristic and spectroscopic properties of the Schiff-base model compounds.
AB  - Two series of conjugated aromatic imines (Schiff-base model compounds) with
      different central groups and various side-group substitutions have been
      synthesized and characterized by elemental analysis, differential scanning
      calorimetry (DSC) technique, hydrogen nuclear magnetic resonance ((1)H NMR),
      Fourier transform infrared (FTIR) and ultra-violet and visible light (UV-vis)
      spectroscopy measurements. The UV-vis absorption of solutions of these compounds
      in dimethylacetamid (DMA), chloroform and methanol was investigated in the
      optical range from 240 to 450nm, where two distinct absorption bands: at 250-280
      and 315-360nm with the different level of absorption have been observed. The
      influence of compound molecular structure and polarity of solvent on the
      absorption spectra and the possible optical transitions have been discussed.
      Structure of diamines in the azomethine models fundamentally affected their
      spectroscopic properties and conjugation of pi-electrons.

PMID- 19748308
TI  - Crystal growth and comparative studies of XRD, spectral studies on new NLO
      crystals: L-Valine and L-valinium succinate.
AB  - Nonlinear optical single crystals of L-valine and L-valinium succinate were grown
      by slow evaporation solution growth method using water as the solvent. Purity of
      crystals was increased by the method of recrystallization. The grown crystals
      were analyzed by the single crystals X-ray diffraction pattern which proved that
      LVS belongs to orthorhombic crystals system. The presence of functional groups
      and modes of vibrations were identified by FT-IR spectroscopy. The chemical
      structure of crystals was established by FT-NMR technique. The transmission range
      of grown crystals was identified by UV-vis-NIR. The transmission region of LVS
      was more effective than LV which could be used for NLO applications. The
      nonlinear optical property of the grown crystals was confirmed by second harmonic
      generation test which shows the suitability of NLO applications.

PMID- 19748309
TI  - Beyond "poke & hope": the next steps for DBS for psychiatric disorders.

PMID- 19748310
TI  - Deciphering the tremor enigma.

PMID- 19748311
TI  - Concerning the observation of an electrical potential at a distance from an
      intracranial electrode contact.

PMID- 19748312
TI  - Epidemiological and clinical relevance of insomnia diagnosis algorithms according
      to the DSM-IV and the International Classification of Sleep Disorders (ICSD).
AB  - BACKGROUND: Although the epidemiology of insomnia in the general population has
      received considerable attention in the past 20 years, few studies have
      investigated the prevalence of insomnia using operational definitions such as
      those set forth in the ICSD and DSM-IV, specifying what proportion of respondents
      satisfied the criteria to reach a diagnosis of insomnia disorder. METHODS: This
      is a cross-sectional study involving 25,579 individuals aged 15 years and over
      representative of the general population of France, the United Kingdom, Germany,
      Italy, Portugal, Spain and Finland. The participants were interviewed on sleep
      habits and disorders managed by the Sleep-EVAL expert system using DSM-IV and
      ICSD classifications. RESULTS: At the complaint level, too short sleep (20.2%),
      light sleep (16.6%), and global sleep dissatisfaction (8.2%) were reported by 37%
      of the subjects. At the symptom level (difficulty initiating or maintaining sleep
      and non-restorative sleep at least 3 nights per week), 34.5% of the sample
      reported at least one of them. At the criterion level, (symptoms+daytime
      consequences), 9.8% of the total sample reported having them. At the diagnostic
      level, 6.6% satisfied the DSM-IV requirement for positive and differential
      diagnosis. However, many respondents failed to meet diagnostic criteria for
      duration, frequency and severity in the two classifications, suggesting that
      multidimensional measures are needed. CONCLUSIONS: A significant proportion of
      the population with sleep complaints do not fit into DSM-IV and ICSD
      classifications. Further efforts are needed to identify diagnostic criteria and
      dimensional measures that will lead to insomnia diagnoses and thus provide a more
      reliable, valid and clinically relevant classification.

PMID- 19748313
TI  - Wake up to insomnia diagnosis: Asking the right questions of who, where, when,
      and what.

PMID- 19748314
TI  - Stress and nursing care needs of women with breast cancer during primary
      treatment: a qualitative study.
AB  - PURPOSE: The primary surgical therapy for breast cancer represents a special
      phase in the course of the disease. The aim of this study was to find out the
      specific strains influencing the women affected during this time, and the needs
      and expectations they had of the nurses. METHOD: In a semistructured interview,
      42 women at an early stage of breast cancer were asked about their strains and
      care needs. RESULTS: The results show that the women interviewed suffer more from
      psychological strains than physical ones, and express the wish for, above all,
      emotional support. Analysis of the interviews provides 4 categories of strains:
      immediate strains regarding the surgery, fear through uncertainty, change of self
      perception and the strains caused by the social environment. Care needs can be
      divided into 3 main areas: wishes for (a) the relationship to the nurses, (b)
      professional competence and (c) the external conditions of care. CONCLUSIONS:
      Nurses can support the women well by listening to them, accepting their emotions
      and informing them in detail. Therewith, they can convey a sense of security to
      the women and help them to maintain hope and the ability to deal with reality.

PMID- 19748315
TI  - The importance of relationships in the experience of cancer: a re-working of the
      policy ideal of the whole-systems approach.
AB  - PURPOSE OF THE RESEARCH: This paper outlines the importance of interpersonal
      familial relationships in how people experience cancer. METHODS AND SAMPLE: This
      paper draws on data from a longitudinal, qualitative study which aimed to explore
      the experiences of people with cancer within the first year following diagnosis.
      The sample included fifteen men with colorectal cancer, 3 women with colorectal
      cancer, twelve women with breast cancer, nine women with gynaecological cancer,
      six women with lung cancer, eleven men with lung cancer and ten men with prostate
      cancer. Four people died during the course of the study and ten people chose to
      withdraw. KEY RESULTS: Close interpersonal relationships were clearly core
      mediating features in how the illness was experienced; for example, presenting
      for symptom investigation was often the result of ongoing interaction and debate
      between partners. We use the idea of the 'joint ownership of cancer' to elucidate
      the role of relationships in experiencing and understanding the disease. We
      propose a re-working of the notion of a whole-systems approach to include not
      just partnership working within health and social care agencies, but centralising
      the patient's interpersonal relationships as critical in each aspect of their
      experience of cancer. CONCLUSIONS: The findings are discussed in terms of the
      need for service delivery and research to be mindful of the relational aspects
      and implications of illness. Nurses can play a key role in how this is
      operationalised in supporting people affected by cancer in the context of their
      relationships.

PMID- 19748316
TI  - Effect of acupressure on chemotherapy-induced nausea and vomiting in gynecologic
      cancer patients in Turkey.
AB  - PURPOSE: The aim of the current study was to assess the effect of acupressure
      applied to the pericardium 6 (P6 or Neiguan) acupuncture point with a wristband
      (Sea-Band) on nausea-vomiting in addition to the standard antiemetic medications
      used to prevent nausea-vomiting due to chemotherapy in gynecologic cancer
      patients. METHOD: In this prospective research we used pre- and posttests. The
      study consisted of 34 patients with gynecologic cancer. RESULTS: We found a
      significant decrease in the patients' mean scores of nausea and the use of
      antiemetic medications following acupressure applied to the patients with a
      wristband, when compared with their mean scores of nausea and the use of
      antiemetic medications prior to the application (p<0.05), and we also observed a
      decline in their mean scores of vomiting and retching episodes; however, this
      decline was not found to be statistically significant (p>0.05). CONCLUSIONS: The
      findings from this study suggest that the acupressure applied to P6 acupuncture
      point with wristbands may be effective in reducing chemotherapy-related nausea
      and may decrease the antiemetic use after chemotherapy. Further research with
      more subjects is needed.

PMID- 19748317
TI  - Surprising variety in energy metabolism within Trypanosomatidae.
AB  - The metabolism of Trypanosomatidae differs significantly between distinct species
      and can even be completely different between various life-cycle stages of the
      same species. It has been proposed that differences in energy metabolism are
      related to differences in nutrient supply in the environments of the various
      trypanosomatids. However, the literature shows that availability of substrates
      does not dictate the type of energy metabolism of trypanosomatids, as Trypanosoma
      theileri, Trypanosoma lewisi and African trypanosomes all live in the bloodstream
      of their mammalian host, but have surprisingly large differences in metabolism.
      Furthermore, in trypanosomatids no obvious relationship exists between energy
      metabolism and phylogeny or mode of transmission. We provide an overview of the
      metabolic capacities in the energy metabolism of distinct trypanosomatids, and
      suggest that these can be divided into four different metabolic categories of
      increasing complexity.

PMID- 19748318
TI  - A simple in vitro PK/PD model system to determine time-kill curves of drugs
      against Mycobacteria.
AB  - In vivo tuberculosis is exposed to continually changing drug concentrations for
      which static minimum inhibitory concentration (MIC) testing may be a poor
      surrogate. While in vitro approaches to determine time-kill curves for
      antibiotics have been widely applied in assessing antimicrobial activity against
      fast growing microorganisms, their availability and application for slow-growing
      microorganisms including Mycobacterium tuberculosis has so far been scarce. Thus,
      we developed a novel simple in vitro pharmacokinetic/pharmacodynamic (PK/PD)
      model for establishing time-kill curves and applied it for evaluating the
      antimicrobial activity of different dosing regimens of isoniazid (INH) against
      Mycobacterium bovis BCG as a surrogate for virulent M. tuberculosis. In the in
      vitro model M. bovis BCG was exposed to INH concentration-time profiles as
      usually encountered during multiple dose therapy with 25, 100 and 300mg/day in
      humans who are fast or slow INH metabolizers. Bacterial killing was followed over
      time by determining viable counts and the resulting time-kill data was analyzed
      using a semi-mechanistic PK/PD model with an adaptive IC(50) function to describe
      the emergence of insensitive populations of bacteria over the course of
      treatment. In agreement with previous studies, the time-kill data suggest that
      AUC(0-24)/MIC is the PK/PD index that is the most explanatory of the
      antimicrobial effect of INH. The presented in vitro PK/PD model and associated
      modeling approach were able to characterize the time-kill kinetics of INH in M.
      bovis BCG, and may in general serve as a potentially valuable, low cost tool for
      the assessment of antibacterial activity in slow-growing organisms in drug
      development and applied pharmacotherapy.

PMID- 19748320
TI  - Uncertain BENEFIT of early interferon beta-1b treatment.

PMID- 19748319
TI  - Long-term effect of early treatment with interferon beta-1b after a first
      clinical event suggestive of multiple sclerosis: 5-year active treatment
      extension of the phase 3 BENEFIT trial.
AB  - BACKGROUND: The Betaferon/Betaseron in newly emerging multiple sclerosis for
      initial treatment (BENEFIT) trial investigated the effect of treatment with
      interferon beta-1b after a clinically isolated syndrome. The 5-year active
      treatment extension compares the effects of early and delayed treatment with
      interferon beta-1b on time to clinically definite multiple sclerosis (CDMS) and
      other disease outcomes, including disability progression. METHODS: Patients with
      a first event suggestive of multiple sclerosis and a minimum of two clinically
      silent lesions in MRI were randomly assigned to receive interferon beta-1b 250
      microg (n=292; early treatment) or placebo (n=176; delayed treatment)
      subcutaneously every other day for 2 years, or until diagnosis of CDMS. All
      patients were then eligible to enter a prospectively planned follow-up phase with
      open-label interferon beta-1b up to a maximum of 5 years after randomisation.
      Patients and study personnel remained unaware of initial treatment allocation
      throughout the study. Primary endpoints were time to CDMS, time to confirmed
      disability progression measured with the expanded disability status scale, and
      the functional assessment of multiple sclerosis trial outcomes index (FAMS-TOI)
      at 5 years. Analysis of the primary endpoints was by intention to treat. This
      trial is registered with ClinicalTrials.gov, number NCT00185211. FINDINGS: 235
      (80%) patients from the early treatment and 123 (70%) from the delayed treatment
      group completed the 5-year study. Early treatment reduced the risk of CDMS by 37%
      (hazard ratio [HR] 0.63, 95% CI 0.48-0.83; p=0.003) compared with delayed
      treatment. The risk for confirmed disability progression was not significantly
      lower in the early treatment group (0.76, 0.52-1.11; p=0.177). At 5 years, median
      FAMS-TOI scores were 125 in both groups. No significant differences in other
      disability related outcomes were recorded. Frequency and severity of adverse
      events remained within the established safety and tolerability profile of
      interferon beta-1b. INTERPRETATION: Effects on the rate of conversion to CDMS and
      the favourable long-term safety and tolerability profile support early initiation
      of treatment with interferon beta-1b, although a delay in treatment by up to 2
      years did not affect long-term disability outcomes. FUNDING: Bayer Schering
      Pharma.

PMID- 19748321
TI  - Low level natural antibodies against phosphorylcholine: a novel risk marker and
      potential mechanism in atherosclerosis and cardiovascular disease.
AB  - Atherosclerosis is an inflammatory condition characterised by an abundance of
      activated immunocompetent cells in plaques which cause cardiovascular disease
      (CVD) when they rupture. Oxidized forms of low density lipoprotein (OxLDL) are a
      major constituent of atherosclerotic plaques and have proinflammatory effects,
      making oxLDL a candidate factor promoting atherosclerosis. In previous studies we
      and others demonstrated that platelet-activating factor (PAF)-like lipids in
      oxLDL may cause oxLDL-induced immune-stimulatory effects. A common denominator is
      phosphorylcholine (PC), a hapten-like epitope which is exposed on OxLDL and some
      microorganisms. We recently demonstrated that anti-PC has anti-inflammatory
      properties and that low levels of anti-PC predict the development of stroke and
      myocardial infarction. We hypothesize that low anti-PC represents a novel
      paradigm as a cause of chronic inflammatory diseases such as atherosclerosis
      where oxidized and/or inflammatory phospholipids play a role. It is possible that
      anti-PC can be used as a novel diagnostic tool and therapy in atherosclerotic
      disease.

PMID- 19748322
TI  - Effects of insulin-like growth factor-1 (IGF-1) receptor signaling on rates of
      apoptosis in retina of dopamine beta hydroxylase (Dbh-/-) knockout mice.
AB  - We have investigated whether insulin-like growth factor-1 (IGF-1) receptor
      signaling alters rates of apoptosis in dopamine beta-hydroxylase (Dbh(-/-))
      knockout mice. Retinal lysates from Dbh(-/-) and their heterozygote littermates
      (Dbh(+/-)) were used to examine the role of norepinephrine in the regulation of
      IGF-1 receptor signaling and apoptosis in the retina. Western blot analysis was
      done for protein levels of total and phosphorylated IGF-1 receptor, insulin
      receptor substrate-1 (IRS-1), insulin receptor substrate-2 (IRS-2), and Akt. A
      caspase 3 ELISA and dopamine ELISA were done on retinal lysates. To verify which
      regions of the retina were undergoing apoptosis, TUNEL labeling was performed. No
      changes in dopamine were noted between the KO and heterozygote mice. IGF-1
      receptor phosphorylation was significantly decreased in Dbh(-/-) mice as compared
      to their heterozygote littermates (P<0.05 vs. heterozygous mice). IRS-1 protein
      phosphorylation was significantly decreased in KO mice (P<0.05 vs. heterozygous
      mice), while no significant changes were noted in IRS-2 protein phosphorylation.
      Akt protein phosphorylation was also reduced in the KO mice, likely leading to
      increased cleaved caspase 3 levels. The increase in apoptosis in the Dbh(-/-)
      mice occurred predominantly in the inner retina. Our results suggest that IGF-1
      receptor signaling is reduced in the retina of mice with dysfunctional adrenergic
      receptor signaling. The data also indicate that IGF-1 receptor signaling occurs
      primarily through IRS-1, rather than IRS-2. The reduction in Akt phosphorylation,
      likely through reduced IGF-1 receptor signaling, could explain the increase in
      cleaved caspase 3, leading to apoptosis. These results suggest that alterations
      in adrenergic receptor signaling modulate IGF-1 receptor signaling, which can
      regulate apoptosis in the retina.

PMID- 19748323
TI  - Liquid chromatography-tandem mass spectrometry method for the quantification of
      dimebon in rat plasma and brain tissue.
AB  - A sensitive high-performance liquid chromatography-positive ion electrospray
      tandem mass spectrometry method was developed and validated for the
      quantification of dimebon in rat plasma and brain tissue. Following liquid-liquid
      extraction, the analyte was separated using a gradient mobile phase on a reversed
      phase column and analyzed by MS/MS in the multiple reaction monitoring mode using
      the respective [M+H](+) ions, m/z 320-277 for dimebon and m/z 407-100 for the
      internal standard. The assay exhibited a linear dynamic range of 0.25-250 ng/mL
      for dimebon in rat plasma and brain tissue. Acceptable precision (<11%) and
      accuracy (100+/-7%) were obtained for concentrations over the standard curve
      range. A run time of 2.5 min for each sample made it possible to analyze more
      than 250 samples per day. The method was successfully applied to quantify dimebon
      concentrations in a rodent pharmacokinetic study. Moreover, it can be believed
      that the assay method in rat plasma would facilitate the ease of adaptability of
      dimebon quantification in human plasma for clinical trials.

PMID- 19748324
TI  - Internally calibrated quantification of VEGF in human plasma by fluorescence
      immunoassays in disposable elastomeric microfluidic devices.
AB  - Herein we report on a proof of principle for the reproducible quantification of
      Vascular Endothelial Growth Factor (VEGF) in human plasma by fluorescence
      sandwich immunoassays using disposable polydimethylsiloxane (PDMS) microfluidic
      chips. The system requires 100 times less sample than typical clinical blood
      tests, while its current quantification limit is established at 4pM. The in-built
      calibration method of spiking the plasma with known concentrations of
      commercially available antigen avoids common sources of error and improves the
      reliability of the test results. The demonstrated technique is important for
      immunoassay applications in fundamental scientific research and "point-of-care"
      (POC) biomedical diagnostics. In particular, the system is immediately applicable
      to microfluidic quantification of VEGF in human plasma in cancer studies.

PMID- 19748325
TI  - Separation of diastereoisomers of Ara-C phosphotriesters using solid phase
      extraction and HPLC for the study of their decomposition kinetic in cell
      extracts.
AB  - Separations of the diastereoisomers of three nucleoside 5'-phosphotriester
      derivatives of Ara-C (tBuSATE, hydroxy tBuSATE and bishydroxy tBuSATE
      phenylphosphotriester derivatives; pronucleotides) were performed by HPLC using
      derivatized cellulose and amylose chiral stationary phases. An optimal baseline
      separation (Rs>1.5) was readily obtained with an amylose based chiral column (AD
      H) used in normal phase mode. This stereospecific HPLC method has been associated
      to a solid phase extraction step using a C18 cartridge and an internal standard
      for the quantification of one nucleoside 5'-phosphotriester derivative in cell
      extracts. After optimization, this method was validated in terms of specificity,
      recovery, linearity, precision and accuracy and detection limit. It was applied
      to the determination of the apparent rate constants of disappearance and half
      lives of each diastereoisomer. This enabled us to conclude that the enzymatic
      activity involved in the first step of the decomposition pathway of the hydroxyl
      tBuSATE phenylphosphotriester of Ara-C is stereoselective and is related to the
      nature of the pyrimidic base.

PMID- 19748326
TI  - Effect of mitiglinide on Streptozotocin-induced experimental type 2 diabetic
      rats: a urinary metabonomics study based on ultra-performance liquid
      chromatography-tandem mass spectrometry.
AB  - Mitiglinide is a new insulinotropic agent of the glinide class and its precise
      mechanism is not very clear yet. In this study, a urinary metabonomics method
      based on ultra-performance liquid chromatography-tandem mass spectrometry was
      developed to study the effect mechanism of mitiglinide on type 2 diabetes
      mellitus. With pattern recognition analysis of urinary metabolite profiles, a
      clear separation between Streptozotocin-induced type 2 diabetic rats and those
      treated with mitiglinide was achieved. Some significantly changed metabolites
      like citrate, creatinine, phenylalanine and bile acids (cholic acid,
      chenodeoxycholic acid and deoxycholic acid) have been identified and used to
      explain the mechanism. This work shows that metabonomics method is a valuable
      tool in drug mechanism study.

PMID- 19748327
TI  - A novel method to detect seven microcystins in hard clam and corbicula fluminea
      by liquid chromatography-tandem mass spectrometry.
AB  - A simple and reliable method to detect seven microcystins in hard clam and
      corbicula fluminea, based on liquid chromatography with electrospray ionization
      and tandem mass spectrometry (LC-ESI-MS/MS), was developed and validated. The
      sample preparation procedure includes extraction of tissue by methanol, followed
      by cleanup on a reversed-phase solid phase extraction (SPE) cartridge. With the
      optimized method, recoveries were between 43.7% and 92.3% for hard clam, 54.3%
      and 93.8% for corbicula fluminea, the relative standard deviations (RSD) were
      less than or equal to 16.2% and 15.7% in hard clam and corbicula fluminea at
      spiking levels of 1 microg/kg, 2 microg/kg and 5 microg/kg for MC-RR, MC-YR, MC
      LR, and MC-LY, and 2 microg/kg, 5 microg/kg and 10 microg/kg for MC-LA, MC-LW and
      MC-LF, respectively, the limits of quantitation (LOQ) of this method were ranged
      from 0.7 microg/kg to 2.0 microg/kg.

PMID- 19748328
TI  - Sensitive determination of kaempferol in rat plasma by high-performance liquid
      chromatography with chemiluminescence detection and application to a
      pharmacokinetic study.
AB  - A simple and sensitive method based on high-performance liquid chromatography
      (HPLC) coupled with chemiluminescence detection was developed for the
      quantitation of kaempferol (KA) in rat plasma. Isorhamnetin (IS) was used as an
      internal standard. Plasma samples were prepared only by acidification with 20%
      phosphoric acid and protein precipitation using methanol. Good separations of
      kaempferol and internal standard were achieved with an isocratic elution using a
      mobile phase consisting of methanol and aqueous 0.4% phosphoric acid (47:53, v/v)
      within 25 min. The detection limit for kaempferol was 1.0x10(-9) g/ml. The mean
      accuracy was within 80.0-100.2%, and the intra- and inter-day precision had RSD
      (%) < 5.0. The sample preparation method was able to produce high recovery (> or
      = 80.0%). The proposed method with wide linear range has been successfully
      applied to a pharmacokinetic study in SD rats after oral administration at a dose
      of 2500 or 1250 mg/kg bodyweight (BW) kaempferol. Kaempferol concentration was
      detectable in plasma up to 24 h post-dosing, and the pharmacokinetic parameters
      of T(max), C(max), AUC(0-infinity), MRT(0-infinity), and T(1/2) of kaempferol
      were reported.

PMID- 19748330
TI  - Distally based anterolateral-thigh (ALT) flap with the aid of multidetector
      computed tomography.
AB  - The applicability of the proximally based pedicled anterolateral thigh (ALT) flap
      has been well described with good results, but the use of a distally based ALT
      flap around the knee has not been fairly presented. The case of a male patient
      with a soft-tissue defect around the knee who underwent skin reconstruction based
      on an ipsilateral distally based ALT flap is presented. Multidetector-computed
      tomography (MDCT) was used to study the vessels of the lower extremity, which
      allowed easy interpretation as it provided anatomical images with three
      dimensional anatomy reconstructions. Because of the knowledge of the anatomical
      connections with the lateral femoral circumflex artery (LFCA) and the superior
      lateral genicular artery (SLGA), the distally based ALT flap could be safely
      transferred. Soft-tissue reconstruction around the knee using the distally based
      ALT flap could also be performed safely and reliably with the aid of MDCT.

PMID- 19748329
TI  - Practice guidelines for the treatment of hepatitis C: recommendations from an
      AISF/SIMIT/SIMAST Expert Opinion Meeting.
AB  - It is increasingly clear that a tailored therapeutic approach to patients with
      hepatitis C virus infection is needed. Success rates in difficult to treat and
      low-responsive hepatitis C virus patients are not completely satisfactory, and
      there is the need to optimise treatment duration and intensity in patients with
      the highest likelihood of response. In addition, the management of special
      patient categories originally excluded from phase III registration trials needs
      to be critically re-evaluated. This article reports the recommendations for the
      treatment of hepatitis C virus infection on an individual basis, drafted by
      experts of three scientific societies.

PMID- 19748331
TI  - Type 2 diabetes management in nurse-led primary healthcare settings in urban and
      rural Cameroon.
AB  - AIMS: To implement a protocol-driven primary nurse-led care for type 2 diabetes
      in rural and urban Cameroon. METHODS: We set-up three primary healthcare clinics
      in Yaounde (Capital city) and two in the Bafut rural health district.
      Participants were 225 (17% rural) patients with known or newly diagnosed type 2
      diabetes, not requiring insulin, referred either from a baseline survey (38
      patients, 17%), or secondarily attracted to the clinics. Protocol-driven glucose
      and blood pressure control were delivered by trained nurses. The main outcomes
      were trajectories of fasting capillary glucose and blood pressure indices, and
      differences in the mean levels between baseline and final visits. RESULTS: The
      total duration of follow-up was 1110 patient-months. During follow-up, there was
      a significant downward trend in fasting capillary glucose overall (p<0.001) and
      in most subgroups of participants. Between baseline and final visits, mean
      fasting capillary glucose dropped by 1.6 mmol/L (95% CI: 0.8-2.3; p< or =0.001).
      Among those with hypertension, blood pressure also decreased significantly for
      systolic and marginally for diastolic blood pressure. No major significant change
      was noticed for body weight. CONCLUSIONS: Nurses may be potential alternatives to
      improve access to diabetes care in settings where physicians are not available.

PMID- 19748332
TI  - Complete suprapatellar plica presenting like a tumor.
AB  - Although synovial plicae of the knee are frequently observed in adults and often
      bilateral, they remain, in most cases, asymptomatic. Pain is thus the most
      commonly encountered symptom. We report the case of an unusual complete
      suprapatellar plica of pseudotumoral aspect. Suprapatellar plicae account for 58
      to 87% of all plicae of the knee and mostly remain asymptomatic except in case of
      a complete septum. A 17-year-old male presented with complaints of his right knee
      with local discomfort for more than one-year duration. The pain mostly arose
      following a prolonged sitting position but with no significant pain in the knee
      otherwise. The presence of an anterolateral suprapatellar mass at clinical
      examination required the need for further tests (standard X-rays and MRI). On MR
      imaging, the liquid aspect of this mass associated with a complete suprapatellar
      bandlike structure separating the sub-quadricipital recess from the knee joint
      suggested the diagnosis of a complete septum type of suprapatellar plica.
      Treatment consisted in an arthroscopic resection. Anatomopathologic verification
      of the removed tissues confirmed the benignant nature of this resected material.
      Outcome was favourable with disappearance of the knee discomfort and
      suprapatellar septum.

PMID- 19748333
TI  - Does lateral versus medial exposure influence total knee tibial component final
      external rotation? A CT based study.
AB  - INTRODUCTION: A previous study demonstrated that performing a total knee
      arthroplasty through a lateral approach including anterior tibial tuberosity
      (ATT) osteotomy (refixed in its original position) presented numerous advantages:
      correcting the preoperative patella lateral tilt and improving postoperative
      patella tracking. We hypothesized that these improvements in patella centering
      were, at least in part, due to an increased external rotation of the tibial
      component. Postoperative scannographic studies were, therefore, undertaken to
      measure tibial component rotation and analyze the results according the medial
      and lateral exposure used. HYPOTHESIS: Rotational positioning of the tibial
      component is influenced by the lateral or medial approach selected at surgery.
      MATERIALS AND METHODS: Forty-five CAT scans, performed according to the protocol
      criteria of the French Hip and Knee Society (SFHG), were studied 3 months
      postoperatively: 15 knees operated through the lateral approach and 30 knees
      operated through a standard medial approach. The total knee utilized in all these
      cases was a posteriorly stabilized, fixed-bearing, design. We measured first the
      angle formed between the perpendicular to the transverse axis of the tibial
      component and the axis joining the ATT to the center of the knee; second we also
      measured the coronal distance between the center of the component and the
      anterior tibial tuberosity (ATT). RESULTS: In the group using the medial
      approach, the lateral position of the ATT was 7 + or - 3mm with a rotation angle
      of 18 degrees . In the group using the lateral approach these measurements were
      respectively 1 + or - 4mm and 2 degrees (p<0.0001). DISCUSSION: External rotation
      of the tibial component is substantially increased by the lateral approach
      compared to the medial approach. Better exposure of the lateral tibial plateau is
      probably responsible of this difference. This increased external rotation
      improves postoperative patella tracking. TYPE OF STUDY: Prospective; comparative;
      non-randomized study; level 3.

PMID- 19748334
TI  - The piston rises again.
AB  - Previous evidence has indicated that the transmembrane signal in bacterial
      chemoeceptors is carried by the piston displacement of a membrane-spanning
      signaling helix. Hendrickson and coworkers (Cheung and Hendrickson, 2009; Moore
      and Hendrickson, 2009) now provide structural evidence that suggests piston
      transmembrane signaling is widely conserved in bacterial receptors that control
      ubiquitous two-component signaling pathways.

PMID- 19748335
TI  - Polyglutamine dances the conformational cha-cha-cha.
AB  - While polyglutamine repeats appear in dozens of human proteins, high-resolution
      structural analysis of these repeats in their native context has eluded
      researchers. Kim et al. now describe multiple crystal structures and demonstrate
      that polyglutamine in huntingtin dances through multiple conformations.

PMID- 19748336
TI  - Keeping an eye on membrane transport by TR-WAXS.
AB  - In this issue of Structure, Andersson et al. apply time-resolved wide angle X-ray
      scattering (TR-WAXS) to follow light-induced conformational changes for both
      bacteriorhodopsin and proteorhodopsin and probe real-time dynamics at atomic
      resolution.

PMID- 19748337
TI  - The nuclear pore complex has entered the atomic age.
AB  - Nuclear pore complexes (NPCs) perforate the nuclear envelope and represent the
      exclusive passageway into and out of the nucleus of the eukaryotic cell. Apart
      from their essential transport function, components of the NPC have important,
      direct roles in nuclear organization and in gene regulation. Because of its
      central role in cell biology, it is of considerable interest to determine the NPC
      structure at atomic resolution. The complexity of these large, 40-60 MDa protein
      assemblies has for decades limited such structural studies. More recently,
      exploiting the intrinsic modularity of the NPC, structural biologists are making
      progress toward understanding this nanomachine in molecular detail. Structures of
      building blocks of the stable, architectural scaffold of the NPC have been
      solved, and distinct models for their assembly proposed. Here we review the
      status of the field and lay out the challenges and the next steps toward a full
      understanding of the NPC at atomic resolution.

PMID- 19748338
TI  - Quantitative determination of the conformational properties of partially folded
      and intrinsically disordered proteins using NMR dipolar couplings.
AB  - Intrinsically disordered proteins (IDPs) inhabit a conformational landscape that
      is too complex to be described by classical structural biology, posing an
      entirely new set of questions concerning the molecular understanding of
      functional biology. The characterization of the conformational properties of
      IDPs, and the elucidation of the role they play in molecular function, is
      therefore one of the major challenges remaining for modern structural biology.
      NMR is the technique of choice for studying this class of proteins, providing
      information about structure, flexibility, and interactions at atomic resolution
      even in completely disordered states. In particular, residual dipolar couplings
      (RDCs) have been shown to be uniquely sensitive and powerful tools for
      characterizing local and long-range structural behavior in disordered proteins.
      In this review we describe recent applications of RDCs to quantitatively describe
      the level of local structure and transient long-range order in IDPs involved in
      viral replication, neurodegenerative disease, and cancer.

PMID- 19748339
TI  - The orientation of a tandem POTRA domain pair, of the beta-barrel assembly
      protein BamA, determined by PELDOR spectroscopy.
AB  - The outer membrane beta-barrel trans-membrane proteins in gram-negative bacteria
      are folded into the membrane with the aid of polypeptide transport-associated
      (POTRA) domains. These domains occur, and probably function, as a tandem array
      situated on the periplasmic side of the outer membrane. Two crystal structures
      and one NMR study have attempted to define the structure and articulation of the
      POTRA domains of the Escherichia coli, prototypic Omp85 protein BamA. We have
      used pulsed electron paramagnetic resonance (EPR) to determine the distance and
      distance distribution between (1-Oxyl-2,2,5,5-tetramethylpyrroline-3-methyl)
      methanethiosulfonate spin labels (MTSSL), placed across the domain interface of
      the first two POTRA domains of BamA. Our results show tightly defined interdomain
      distance distributions that indicate a well-defined domain orientation.
      Examination of the known structures revealed that none of them fitted the EPR
      data. A combination of EPR and NMR data was used to generate converged structures
      with defined domain-domain orientation.

PMID- 19748340
TI  - Structural analysis of sensor domains from the TMAO-responsive histidine kinase
      receptor TorS.
AB  - Histidine kinase receptors respond to diverse signals and mediate signal
      transduction across the plasma membrane in all prokaryotes and certain
      eukaryotes. Each receptor is part of a two-component system that regulates a
      particular cellular process. Organisms that use trimethylamine-N-oxide (TMAO) as
      a terminal electron acceptor typically control their anaerobic respiration
      through the TMAO reductase (Tor) pathway, which the TorS histidine kinase
      activates when sensing TMAO in the environment. We have determined crystal
      structures for the periplasmic sensor domains of TorS receptors from Escherichia
      coli and Vibrio parahaemolyticus. TorS sensor domains have a novel fold
      consisting of a membrane-proximal right-handed four-helical bundle and a membrane
      distal left-handed four-helical bundle, but conformational dispositions differ
      significantly in the two structures. Isolated TorS sensor domains dimerize in
      solution; and from comparisons with dimeric NarX and Tar sensors, we postulate
      that signaling through TorS dimers involves a piston-type displacement between
      helices.

PMID- 19748341
TI  - Secondary structure of Huntingtin amino-terminal region.
AB  - Huntington's disease is a genetic neurodegenerative disorder resulting from
      polyglutamine (polyQ) expansion (>36Q) within the first exon of Huntingtin (Htt)
      protein. We applied X-ray crystallography to determine the secondary structure of
      the first exon (EX1) of Htt17Q. The structure of Htt17Q-EX1 consists of an amino
      terminal alpha helix, poly17Q region, and polyproline helix formed by the proline
      rich region. The poly17Q region adopts multiple conformations in the structure,
      including alpha helix, random coil, and extended loop. The conformation of the
      poly17Q region is influenced by the conformation of neighboring protein regions,
      demonstrating the importance of the native protein context. We propose that the
      conformational flexibility of the polyQ region observed in our structure is a
      common characteristic of many amyloidogenic proteins. We further propose that the
      pathogenic polyQ expansion in the Htt protein increases the length of the random
      coil, which promotes aggregation and facilitates abnormal interactions with other
      proteins in cells.

PMID- 19748342
TI  - Insights into how nucleotide-binding domains power ABC transport.
AB  - The mechanism by which nucleotide-binding domains (NBDs) of ABC transporters
      power the transport of substrates across cell membranes is currently unclear.
      Here we report the crystal structure of an NBD, FbpC, from the Neisseria
      gonorrhoeae ferric iron uptake transporter with an unusual and substantial domain
      swap in the C-terminal regulatory domain. This entanglement suggests that FbpC is
      unable to open to the same extent as the homologous protein MalK. Using molecular
      dynamics we demonstrate that this is not the case: both NBDs open rapidly once
      ATP is removed. We conclude from this result that the closed structures of FbpC
      and MalK have higher free energies than their respective open states. This result
      has important implications for our understanding of the mechanism of power
      generation in ABC transporters, because the unwinding of this free energy ensures
      that the opening of these two NBDs is also powered.

PMID- 19748343
TI  - Probing the accessibility of the Mn(4)Ca cluster in photosystem II: channels
      calculation, noble gas derivatization, and cocrystallization with DMSO.
AB  - Using the 2.9 A resolution structure of the membrane-intrinsic protein-cofactor
      complex photosystem II (PSII) from the cyanobacterium Thermosynechococcus
      elongatus, we calculated and characterized nine possible substrate/product
      channels leading to/away from the Mn(4)Ca cluster, where water is oxidized to
      dioxygen, protons, and electrons. Five narrow channels could function in proton
      transport, assuming that no large structural changes are associated with water
      oxidation. Four wider channels could serve to supply water to or remove oxygen
      from the Mn(4)Ca cluster. One of them might be regulated by conformational
      changes of Lys134 in subunit PsbU. Data analyses of Kr derivatized crystals and
      complexes with dimethyl sulfoxide (DMSO) confirm the accessibility of the
      proposed dioxygen channels to other molecules. Results from Xe derivatization
      suggest that the lipid clusters within PSII could serve as a drain for oxygen
      because of their predominant hydrophobic character and mediate dioxygen release
      from the lumen.

PMID- 19748344
TI  - Subunit architecture of multiprotein assemblies determined using restraints from
      gas-phase measurements.
AB  - Protein interaction networks are becoming an increasingly important area of
      research within structural genomics. Here we present an ion mobility-mass
      spectrometry approach capable of distinguishing the overall subunit architecture
      of protein complexes. The approach relies on the simultaneous measurement in the
      gas phase of the mass and size of intact assemblies and subcomplexes. These data
      are then used as restraints to generate topological models of protein complexes.
      To test and develop our method, we have chosen two well-characterized homo
      dodecameric protein complexes: ornithine carbamoyl transferase and glutamine
      synthetase. By forming subcomplexes related to the comparative strength of the
      subunit interfaces, acquiring ion mobility data, and subsequent modeling, we show
      that these "building blocks" retain their native interactions and do not undergo
      major rearrangement in either solution or gas phases. We apply this approach to
      study two subcomplexes of the human eukaryotic initiation factor 3, for which
      there is no high-resolution structure.

PMID- 19748345
TI  - Probing the "dark matter" of protein fold space.
AB  - We used a protein structure prediction method to generate a variety of folds as
      alpha-carbon models with realistic secondary structures and good hydrophobic
      packing. The prediction method used only idealized constructs that are not based
      on known protein structures or fragments of them, producing an unbiased
      distribution. Model and native fold comparison used a topology-based method as
      superposition can only be relied on in similar structures. When all the models
      were compared to a nonredundant set of all known structures, only one-in-ten were
      found to have a match. This large excess of novel folds was associated with each
      protein probe and if true in general, implies that the space of possible folds is
      larger than the space of realized folds, in much the same way that sequence-space
      is larger than fold-space. The large excess of novel folds exhibited no unusual
      properties and has been likened to cosmological dark matter.

PMID- 19748346
TI  - Structural polymorphism of the ParM filament and dynamic instability.
AB  - Segregation of the R1 plasmid in bacteria relies on ParM, an actin homolog that
      segregates plasmids by switching between cycles of polymerization and
      depolymerization. We find similar polymerization kinetics and stability in the
      presence of either ATP or GTP and a 10-fold affinity preference for ATP over GTP.
      We used electron cryo-microscopy to evaluate the heterogeneity within ParM
      filaments. In addition to variable twist, ParM has variable axial rise, and both
      parameters are coupled. Subunits in the same ParM filaments can exist in two
      different structural states, with the nucleotide-binding cleft closed or open,
      and the bound nucleotide biases the distribution of states. The interface between
      protomers is different between these states, and in neither state is it similar
      to F-actin. Our results suggest that the closed state of the cleft is required
      but not sufficient for ParM polymerization, and provide a structural basis for
      the dynamic instability of ParM filaments.

PMID- 19748347
TI  - Structural dynamics of light-driven proton pumps.
AB  - Bacteriorhodopsin and proteorhodopsin are simple heptahelical proton pumps
      containing a retinal chromophore covalently bound to helix G via a protonated
      Schiff base. Following the absorption of a photon, all-trans retinal is
      isomerized to a 13-cis conformation, initiating a sequence of conformational
      changes driving vectorial proton transport. In this study we apply time-resolved
      wide-angle X-ray scattering to visualize in real time the helical motions
      associated with proton pumping by bacteriorhodopsin and proteorhodopsin. Our
      results establish that three conformational states are required to describe their
      photocycles. Significant motions of the cytoplasmic half of helix F and the
      extracellular half of helix C are observed prior to the primary proton transfer
      event, which increase in amplitude following proton transfer. These results both
      simplify the structural description to emerge from intermediate trapping studies
      of bacteriorhodopsin and reveal shared dynamical principles for proton pumping.

PMID- 19748348
TI  - Amino acid signaling to TOR activation: Vam6 functioning as a Gtr1 GEF.
AB  - In this issue of Molecular Cell, Binda et al. identify Vam6/Vps39 as a guanine
      nucleotide exchange factor for Gtr1, a Rag family GTPase, to promote TORC1
      activation in response to amino acids.

PMID- 19748349
TI  - The alternating power stroke of a 6-cylinder AAA protease chaperone engine.
AB  - In this issue of Molecular Cell, Augustin et al. (2009) describe the regulatory
      coupling of adjacent ATP subunits in the mitochondrial AAA protease ring along
      with the responsible molecular determinants and uncover its importance for
      membrane dislocation of substrates.

PMID- 19748350
TI  - Resolving the CSN and CAND1 paradoxes.
AB  - In this issue of Molecular Cell, Schmidt et al. (2009) untangle the interplay
      between the COP9 signalosome (CSN), cullin-associated and neddylation-dissociated
      1 (CAND1) protein, and cullin-RING ubiquitin ligases (CRLs).

PMID- 19748351
TI  - XPD helicase speeds through a molecular traffic jam.
AB  - Helicases and other DNA translocases must travel along crowded substrates. In
      this issue, Honda et al. (2009) report that the archaeal XPD helicase can bypass
      a single-stranded DNA-binding protein without either molecule being ejected from
      the DNA.

PMID- 19748352
TI  - Fine-tuning of the unfolded protein response: Assembling the IRE1alpha
      interactome.
AB  - Endoplasmic reticulum (ER) stress is a hallmark feature of secretory cells and
      many diseases, including cancer, neurodegeneration, and diabetes. Adaptation to
      protein-folding stress is mediated by the activation of an integrated signal
      transduction pathway known as the unfolded protein response (UPR). The UPR
      signals through three distinct stress sensors located at the ER membrane
      IRE1alpha, ATF6, and PERK. Although PERK and IRE1alpha share functionally similar
      ER-luminal sensing domains and both are simultaneously activated in cellular
      paradigms of ER stress in vitro, they are selectively engaged in vivo by the
      physiological stress of unfolded proteins. The differences in terms of tissue
      specific regulation of the UPR may be explained by the formation of distinct
      regulatory protein complexes. This concept is supported by the recent
      identification of adaptor and modulator proteins that directly interact with
      IRE1alpha. In this Review, we discuss recent evidence supporting a model where
      IRE1alpha signaling emerges as a highly regulated process, controlled by the
      formation of a dynamic scaffold onto which many regulatory components assemble.

PMID- 19748353
TI  - The Vam6 GEF controls TORC1 by activating the EGO complex.
AB  - The target of rapamycin complex 1 (TORC1) is a central regulator of eukaryotic
      cell growth that is activated by a variety of hormones (e.g., insulin) and
      nutrients (e.g., amino acids) and is deregulated in various cancers. Here, we
      report that the yeast Rag GTPase homolog Gtr1, a component of the vacuolar
      membrane-associated EGO complex (EGOC), interacts with and activates TORC1 in an
      amino-acid-sensitive manner. Expression of a constitutively active (GTP-bound)
      Gtr1(GTP), which interacted strongly with TORC1, rendered TORC1 partially
      resistant to leucine deprivation, whereas expression of a growth inhibitory, GDP
      bound Gtr1(GDP), caused constitutively low TORC1 activity. We also show that the
      nucleotide-binding status of Gtr1 is regulated by the conserved guanine
      nucleotide exchange factor (GEF) Vam6. Thus, in addition to its regulatory role
      in homotypic vacuolar fusion and vacuole protein sorting within the HOPS complex,
      Vam6 also controls TORC1 function by activating the Gtr1 subunit of the EGO
      complex.

PMID- 19748354
TI  - An intersubunit signaling network coordinates ATP hydrolysis by m-AAA proteases.
AB  - Ring-shaped AAA+ ATPases control a variety of cellular processes by substrate
      unfolding and remodeling of macromolecular structures. However, how ATP
      hydrolysis within AAA+ rings is regulated and coupled to mechanical work is
      poorly understood. Here we demonstrate coordinated ATP hydrolysis within m-AAA
      protease ring complexes, conserved AAA+ machines in the inner membrane of
      mitochondria. ATP binding to one AAA subunit inhibits ATP hydrolysis by the
      neighboring subunit, leading to coordinated rather than stochastic ATP hydrolysis
      within the AAA ring. Unbiased genetic screens define an intersubunit signaling
      pathway involving conserved AAA motifs and reveal an intimate coupling of ATPase
      activities to central AAA pore loops. Coordinated ATP hydrolysis between adjacent
      subunits is required for membrane dislocation of substrates, but not for
      substrate processing. These findings provide insight into how AAA+ proteins
      convert energy derived from ATP hydrolysis into mechanical work.

PMID- 19748355
TI  - F-box-directed CRL complex assembly and regulation by the CSN and CAND1.
AB  - The COP9 signalosome (CSN) is thought to maintain the stability of cullin-RING
      ubiquitin ligases (CRL) by limiting the autocatalytic destruction of substrate
      adapters such as F box proteins (FBPs). CAND1, a protein associated with
      unneddylated CUL1, was proposed to assist in this role in an as yet unclear
      fashion. We found that only a subset of Schizosaccharomyces pombe FBPs, which
      feature a critical F box proline that promotes their interaction with CUL1,
      required CSN for stability. Unlike the CRL3 adaptor Btb3p, none of the CSN
      sensitive FBPs were affected by deletion of ubp12. Contrary to current models,
      CAND1 does not control adaptor stability but maintains the cellular balance of
      CRL1 complexes by preventing rare FBPs from being outcompeted for binding to CUL1
      by more ample adapters. These findings were integrated into a refined model of
      CRL control in which substrate availability toggles CRLs between independent CSN
      and CAND1 cycles.

PMID- 19748356
TI  - Structure of the Yeast DEAD box protein Mss116p reveals two wedges that crimp
      RNA.
AB  - The yeast DEAD box protein Mss116p is a general RNA chaperone that functions in
      mitochondrial group I and II intron splicing, translational activation, and RNA
      end processing. Here we determined high-resolution X-ray crystal structures of
      Mss116p complexed with an RNA oligonucleotide and ATP analogs AMP-PNP, ADP
      BeF(3)(-), or ADP-AlF(4)(-). The structures show the entire helicase core acting
      together with a functionally important C-terminal extension. In all structures,
      the helicase core is in a closed conformation with a wedge alpha helix bending
      RNA 3' of the central bound nucleotides, as in previous DEAD box protein
      structures. Notably, Mss116p's C-terminal extension also bends RNA 5' of the
      central nucleotides, resulting in RNA crimping. Despite reported functional
      differences, we observe few structural changes in ternary complexes with
      different ATP analogs. The structures constrain models of DEAD box protein
      function and reveal a strand separation mechanism in which a protein uses two
      wedges to act as a molecular crimper.

PMID- 19748357
TI  - miR-24 Inhibits cell proliferation by targeting E2F2, MYC, and other cell-cycle
      genes via binding to "seedless" 3'UTR microRNA recognition elements.
AB  - miR-24, upregulated during terminal differentiation of multiple lineages,
      inhibits cell-cycle progression. Antagonizing miR-24 restores postmitotic cell
      proliferation and enhances fibroblast proliferation, whereas overexpressing miR
      24 increases the G1 compartment. The 248 mRNAs downregulated upon miR-24
      overexpression are highly enriched for DNA repair and cell-cycle regulatory genes
      that form a direct interaction network with prominent nodes at genes that enhance
      (MYC, E2F2, CCNB1, and CDC2) or inhibit (p27Kip1 and VHL) cell-cycle progression.
      miR-24 directly regulates MYC and E2F2 and some genes that they transactivate.
      Enhanced proliferation from antagonizing miR-24 is abrogated by knocking down
      E2F2, but not MYC, and cell proliferation, inhibited by miR-24 overexpression, is
      rescued by miR-24-insensitive E2F2. Therefore, E2F2 is a critical miR-24 target.
      The E2F2 3'UTR lacks a predicted miR-24 recognition element. In fact, miR-24
      regulates expression of E2F2, MYC, AURKB, CCNA2, CDC2, CDK4, and FEN1 by
      recognizing seedless but highly complementary sequences.

PMID- 19748358
TI  - The interaction of NSBP1/HMGN5 with nucleosomes in euchromatin counteracts linker
      histone-mediated chromatin compaction and modulates transcription.
AB  - Structural changes in specific chromatin domains are essential to the orderly
      progression of numerous nuclear processes, including transcription. We report
      that the nuclear protein NSBP1 (HMGN5), a recently discovered member of the HMGN
      nucleosome-binding protein family, is specifically targeted by its C-terminal
      domain to nucleosomes in euchromatin. We find that the interaction of NSBP1 with
      nucleosomes alters the compaction of cellular chromatin and that in living cells,
      NSBP1 interacts with linker histones. We demonstrate that the negatively charged
      C-terminal domain of NSBP1 interacts with the positively charged C-terminal
      domain of H5 and that NSBP1 counteracts the linker histone-mediated compaction of
      a nucleosomal array. Dysregulation of the cellular levels of NSBP1 alters the
      transcription level of numerous genes. We suggest that mouse NSBP1 is an
      architectural protein that binds preferentially to euchromatin and modulates the
      fidelity of the cellular transcription profile by counteracting the chromatin
      condensing activity of linker histones.

PMID- 19748359
TI  - Structural and functional insights into the roles of the Mms21 subunit of the
      Smc5/6 complex.
AB  - The Smc5/6 complex is an evolutionarily conserved chromosomal ATPase required for
      cell growth and DNA repair. Its Mms21 subunit supports both functions by docking
      to the arm region of Smc5 and providing SUMO ligase activity. Here, we report the
      crystal structure of Mms21 in complex with the Smc5 arm. Our structure revealed
      two distinct structural and functional domains of the Smc5-bound Mms21: its N
      terminal half is dedicated to Smc5 binding by forming a helix bundle with a
      coiled-coil structure of Smc5; its C-terminal half includes the SUMO ligase
      domain, which adopts a new type of RING E3 structure. Mutagenesis and structural
      analyses showed that the Mms21-Smc5 interface is required for cell growth and
      resistance to DNA damage, while the unique Mms21 RING domain confers specificity
      to the SUMO E2-E3 interaction. Through structure-based dissection of Mms21
      functions, our studies establish a framework for understanding its roles in the
      Smc5/6 complex.

PMID- 19748360
TI  - Structure of the Siz/PIAS SUMO E3 ligase Siz1 and determinants required for SUMO
      modification of PCNA.
AB  - Siz1 is a founding member of the Siz/PIAS RING family of SUMO E3 ligases. The X
      ray structure of an active Siz1 ligase revealed an elongated tripartite
      architecture comprised of an N-terminal PINIT domain, a central zinc-containing
      RING-like SP-RING domain, and a C-terminal domain we term the SP-CTD. Structure
      based mutational analysis and biochemical studies show that the SP-RING and SP
      CTD are required for activation of the E2 approximately SUMO thioester, while the
      PINIT domain is essential for redirecting SUMO conjugation to the proliferating
      cell nuclear antigen (PCNA) at lysine 164, a nonconsensus lysine residue that is
      not modified by the SUMO E2 in the absence of Siz1. Mutational analysis of Siz1
      and PCNA revealed surfaces on both proteins that are required for efficient SUMO
      modification of PCNA in vitro and in vivo.

PMID- 19748361
TI  - The effect of replication initiation on gene amplification in the rDNA and its
      relationship to aging.
AB  - In eukaryotes, the ribosomal DNA (rDNA) consists of long tandem repeat arrays.
      These repeated genes are unstable because homologous recombination between them
      results in copy number loss. To maintain high copy numbers, yeast has an
      amplification system that works through a pathway involving the replication fork
      barrier site and unequal sister chromatid recombination. In this study, we show
      that an active replication origin is essential for amplification, and the
      amplification rate correlates with origin activity. Moreover, origin activity
      affects the levels of extrachromosomal rDNA circles (ERC) that are thought to
      promote aging. Surprisingly, we found that reduction in ERC level results in
      shorter life span. We instead show that life span correlates with rDNA stability,
      which is preferentially reduced in mother cells, and that episomes can induce
      rDNA instability. These data support a model in which rDNA instability itself is
      a cause of aging in yeast.

PMID- 19748362
TI  - Single-molecule analysis reveals differential effect of ssDNA-binding proteins on
      DNA translocation by XPD helicase.
AB  - An encounter between a DNA-translocating enzyme and a DNA-bound protein must
      occur frequently in the cell, but little is known about its outcome. Here we
      developed a multicolor single-molecule fluorescence approach to simultaneously
      monitor single-stranded DNA (ssDNA) translocation by a helicase and the fate of
      another protein bound to the same DNA. Distance-dependent fluorescence quenching
      by the iron-sulfur cluster of the archaeal XPD (Rad3) helicase was used as a
      calibrated proximity signal. Despite the similar equilibrium DNA-binding
      properties, the two cognate ssDNA-binding proteins RPA1 and RPA2 differentially
      affected XPD translocation. RPA1 competed with XPD for ssDNA access. In contrast,
      RPA2 did not interfere with XPD-ssDNA binding but markedly slowed down XPD
      translocation. Mechanistic models of bypassing DNA-bound proteins by the Rad3
      family helicases and their biological implications are discussed.

PMID- 19748363
TI  - Checkpoint signaling from a single DNA interstrand crosslink.
AB  - DNA interstrand crosslinks (ICLs) are the most toxic lesions induced by
      chemotherapeutic agents such as mitomycin C and cisplatin. By covalently linking
      both DNA strands, ICLs prevent DNA melting, transcription, and replication.
      Studies on ICL signaling and repair have been limited, because these drugs
      generate additional DNA lesions that trigger checkpoint signaling. Here, we
      monitor sensing, signaling from, and repairing of a single site-specific ICL in
      cell-free extract derived from Xenopus eggs and in mammalian cells. Notably, we
      demonstrate that ICLs trigger a checkpoint response independently of origin
      initiated DNA replication and uncoupling of DNA polymerase and DNA helicase. The
      Fanconi anemia pathway acts upstream of RPA-ATR-Chk1 to generate the ICL signal.
      The system also repairs ICLs in a reaction that involves extensive, error-free
      DNA synthesis. Repair occurs by both origin-dependent and origin-independent
      mechanisms. Our data suggest that cell sensitivity to crosslinking agents results
      from both checkpoint and DNA repair defects.

PMID- 19748364
TI  - Recruitment of fanconi anemia and breast cancer proteins to DNA damage sites is
      differentially governed by replication.
AB  - Fanconi anemia (FA) is characterized by cellular hypersensitivity to DNA
      crosslinking agents, but how the Fanconi pathway protects cells from DNA
      crosslinks and whether FA proteins act directly on crosslinks remain unclear. We
      developed a chromatin-IP-based strategy termed eChIP and detected association of
      multiple FA proteins with DNA crosslinks in vivo. Interdependence analyses
      revealed that crosslink-specific enrichment of various FA proteins is controlled
      by distinct mechanisms. BRCA-related FA proteins (BRCA2, FANCJ/BACH1, and
      FANCN/PALB2), but not FA core and I/D2 complexes, require replication for their
      crosslink association. FANCD2, but not FANCJ and FANCN, requires the FA core
      complex for its recruitment. FA core complex requires nucleotide excision repair
      proteins XPA and XPC for its association. Consistent with the distinct
      recruitment mechanism, recombination-independent crosslink repair was inversely
      affected in cells deficient of FANC-core versus BRCA-related FA proteins. Thus,
      FA proteins participate in distinct DNA damage response mechanisms governed by
      DNA replication status.

PMID- 19748365
TI  - [Pain and schizophrenia: myth and reality].
AB  - INTRODUCTION: The International Association for the Study of Pain (IAPS), in
      1986, defined pain as "an unpleasant sensory and emotional experience associated
      with actual or potential tissue damage, or described in terms of such damage".
      Thus, the few studies on this phenomenon conducted on schizophrenic patients did
      not result in a firm consensus; certain studies showed that such patients seemed
      to have a higher threshold against pain (hypoalgesia) than healthy subjects,
      whilst other studies showed that the threshold is the same, but the absence of
      expressing the pain would be due to the pathology itself (non-expression of the
      pain, denial). Insensitivity to pain would be the consequence of a complex
      reaction between a biological sensorial abnormality and the psychopathology of
      schizophrenia itself (including the affective processes). Hence, various
      hypotheses referring to biological, psychological and sociological mechanisms
      have been proposed. BIOLOGICAL THEORIES: Various other hypotheses based on
      biological factors have been suggested. One of the interesting biologically-based
      hypotheses postulates that the insensitivity is due to a dysregulation of N
      methyl-d-aspartate (NMDA). The biological factors are still not fully explored
      and would only explain in part the phenomenon of the apparent insensitivity to
      pain of individuals with schizophrenia. PSYCHOLOGICAL THEORIES: The thresholds of
      pain and a higher level of tolerance could be explained by an indifference to
      external stimuli and by inappropriate mental functions for these tests. The
      deficit is situated, therefore, both in the sensory discrimination of the
      stimulus (biological function) but also in the interpretation (cognitive and
      emotional functions). These different hypotheses (biological and psychological)
      might explain the insensitivity to pain of schizophrenic patients. PAIN AND
      SCHIZOPHRENIA: THE REALITY: Schizophrenic patients have a sensitivity to pain
      which is identical to that of healthy subjects. The apparent analgesia would be
      the result of a denial "attitude", a different manner of expressing pain in
      relation with the non-verbal communication difficulties, and not an alteration in
      the brain functions nor a biological anomaly. Diverse methodological biases arise
      from the studies of pain in patients with schizophrenia.

PMID- 19748366
TI  - [Homicide and major mental disorder: what are the social, clinical, and forensic
      differences between murderers with a major mental disorder and murderers without
      any mental disorder?].
AB  - OBJECTIVES: To establish the social, clinical, and forensic differences between
      murderers suffering from a major mental disorder and murderers without any
      psychiatric disorder and, in particular, to compare their respective records of
      psychiatric symptoms and their respective relationship with their victims.
      METHOD: We studied 210 forensic examinations of murderers, the offences related
      to the murders, and the social and clinical information collected from
      psychiatric court reports on persons convicted of homicide. Firstly, we
      identified the socio-demographic, clinical and criminological profiles of 210
      murderers from which were distinguished murderers with major mental disorder.
      Then, we compared the profiles of murderers suffering from a major mental
      disorder with those of murderers without any mental disease. In other words, we
      compared 37 persons affected with major mental disorder (schizophrenia, paranoiac
      delusional disorder, and affective disorder) with 73 persons without any mental
      disorder. We deliberately excluded subjects with personality disorder or abuse
      of/dependency on drugs, mental retardation or dementia. RESULTS: With the
      exception of certain variables, murderers with major mental disorder have the
      same characteristics as others murderers: young man, living alone, with
      psychiatric and offence records and substance abuse. Murderers with major mental
      disorder are older (37.8 versus 31.7 years old) than perpretators without any
      mental disorder, and the former have a psychiatric record more often than the
      latter (81 versus 32.9%). In addition, contrary to the latter, the former show
      clinical symptoms of a psychopathological process. Depression, delusional and
      suicidal ideas are frequent among murderers with a major mental disorder, whereas
      the persons without mental disorder quarrel or have a row with their victim just
      before their crime. The victim was known to the perpetrator significantly more
      often in the major mental disorder group than in the no mental disorder group
      (94,6 versus 76,7%, p=0,008). The most major mental disorders' homicide was more
      likely to be against intimates than strangers. The application of the former
      article 64 or the present article 122-1 of the French Criminal Code are envisaged
      more often in the major mental disorder group than in the no mental disorder
      group. CONCLUSION: The main difference between murderers with a major mental
      disorder and murderers without any mental disorder is the psychopathology of the
      morbid process which underlies the homicide. Impairment of judgment at the time
      of the crime should be taken into account. As a clinician, we should focus our
      attention on general risk factors of violence and homicide (male, young,
      underprivileged class, abuse of alcohol) and on more specific factors (mental
      disorder co-morbidities...). To these factors should be added the dynamic
      characteristics of the meeting of the protagonists.

PMID- 19748367
TI  - [Compliance of long-acting atypical antipsychotics: from an image problem to a
      question of indication].
AB  - This paper focuses on the questions asked to practitioners regarding compliance
      to new long-acting atypical antipsychotics (LAAA): how does the comprehensive
      approach of patients' and carers' attitudes facing treatment challenge it?
      OBJECTIVES: A review of recent literature shows that LAAA, are still suffering
      from an "image problem". We aim to describe these negative beliefs and suggest
      that LAAA indications be reconsidered. METHOD: Following a comprehensive
      approach, we interpreted our review on the basis of anthropological criteria. We
      focused on value-based health and disease models that organize the attitude of
      patients and carers regarding the depot injection. RESULTS: Multiple negative
      beliefs attached to the pain, side-effects, and stigmas are well-known to impair
      adhesion to treatment. Carers understand disease as a lack of insight. Patients
      experience it as a threat for the Self and a loss of autonomy. The nurse-patient
      relationship involving injections is an important factor of compliance. When time
      is devoted by the carer to paying attention to the patient's experience, in order
      to perceive the patient as a participant, patients are more likely to adopt the
      injectable route themselves. By doing so, the patient considers the injection as
      a "protective net" a "lesser evil" by integrating it within his(her) biography.
      DISCUSSION: A comprehensive approach links the lack of insight to the patient's
      perception of stigma. Hope for recovery is related by the person him(her)self to
      his(her) own ability for autonomy. Persons with schizophrenia usually struggle
      for norms (agonomia). This trend has to be taken into account. LAAA are better
      indicated when patients are compliant. There is no indication when patients are
      "pure agonomics" and fight to deny both stigma and medication.

PMID- 19748368
TI  - [Study on clozapine treatment at the Charles Perrens Hospital in Bordeaux, 15
      years after its marketing].
AB  - INTRODUCTION: The international consensus conferences concerning schizophrenia
      and the authorization to market (French AMM) reserve this molecule for the
      treatment of resistant schizophrenia. Resistant schizophrenia, as defined by the
      marketing authorisation, corresponds to the absence of improvement in a patient's
      state despite two successive treatments with antipsychotics, or at least an
      atypical drug at an adequate dose for a sufficient length of time. OBJECTIVES:
      Our investigation compares hospital practices to the marketing authorisation and
      guidelines regarding resistant schizophrenia. METHODS: All clozapine
      prescriptions delivered by the pharmacists at the Charles Perrens Hospital were
      recorded during the month of February 2007. General information concerning the
      patient and his or her treatment were collected, based on different support teams
      set up in the hospital. First, the hospital administrative program was used to
      manage the patients. Then, the treatment establishment form, filled out by
      psychiatrists before the beginning of the treatment, listed all previous
      treatments given to the patient and indicated any inefficacy or intolerances to
      prior treatments. Then, a program monitored the delivery of this molecule and
      finally, prescriptions were recorded to describe present treatment. RESULTS: Our
      study consisted of 61 patients, mostly male subjects averaging 40 years of age,
      single, who had been under psychiatric care for about 15 years, and were, for the
      most part, professionally inactive. Clozapine was prescribed for schizophrenic
      (90%) and for bipolar patients (10%). Clozapine was also often prescribed for
      patients whose illness had not improved with prior treatments. The average dose
      was of 489 mg/day for patients considered stable, i.e., those for whom clozapine
      was prescribed with efficacy observed for a sufficiently long time. It was
      associated in 88% of all cases with another psychotropic: anxiolytic (68% of
      cases), normothymic (26% of cases), antidepressant (16%) and antipsychotic (42%).
      DISCUSSION: In practice, clozapine seems to be efficient in bipolar disorders,
      although the marketing authorisation does not envisage this indication. It is
      never prescribed first, as some recommendations indicate, even though the follow
      up of certain treatments does not always seem adequate to appreciate their non
      effectiveness. Seldom prescribed alone, clozapine is often associated with
      another antipsychotic, a practice not favoured by many experts. Our investigation
      thus confirms the increase in co-prescriptions, particularly in hospital, for
      patients who have not improved with clozapine alone, a case that is barely taken
      into consideration in consensus conferences. With the lack of innovative
      molecules, psychiatrists are prompted to associate several antipsychotics, with
      the risk of supporting iatrogenic medication, whereas the experts reserve the
      relevance of such associations because of a lack of randomised studies.

PMID- 19748369
TI  - [Drawing up guidelines for the attendance of physical health of patients with
      severe mental illness].
AB  - INTRODUCTION: Having a mental illness has been and remains even now, a strong
      barrier to effective medical care. Most mental illness, such as schizophrenia,
      bipolar disorder, and depression are associated with undue medical morbidity and
      mortality. It represents a major health problem, with a 15 to 30 year shorter
      lifetime compared with the general population. METHODS: Based these facts, a
      workshop was convened by a panel of specialists: psychiatrists, endocrinologists,
      cardiologists, internists, and pharmacologists from some French hospitals to
      review the information relating to the comorbidity and mortality among the
      patients with severe mental illness, the risks with antipsychotic treatment for
      the development of metabolic disorders and finally cardiovascular disease. The
      French experts strongly agreed on these points: that the patients with severe
      mental illness have a higher rate of preventable risk factors such as smoking,
      addiction, poor diet, lack of exercise; the recognition and management of
      morbidity are made more difficult by barriers related to patients, the illness,
      the attitudes of medical practitioners, and the structure of healthcare delivery
      services; and improved detection and treatment of comorbidity medical illness in
      people with severe mental illness will have significant benefits for their
      psychosocial functioning and overall quality of life. GUIDELINES FOR INITIATING
      ANTIPSYCHOTIC THERAPY: Based on these elements, the French experts propose
      guidelines for practising psychiatrists when initiating and maintaining therapy
      with antipsychotic compounds. The aim of the guidelines is practical and concerns
      the detection of medical illness at the first episode of mental illness,
      management of comorbidity with other specialists, family practitioner and follow
      up with some key points. The guidelines are divided into two major parts. The
      first part provides: a review of mortality and comorbidity of patients with
      severe mental illness: the increased morbidity and mortality are primarily due to
      premature cardiovascular disease (myocardial infarction, stroke...).The
      cardiovascular events are strongly linked to non modifiable risk factors such as
      age, gender, personal and/or family history, but also to crucial modifiable risk
      factors, such as overweight and obesity, dyslipidemia, diabetes, hypertension and
      smoking. Although these classical risk factors exist in the general population,
      epidemiological studies suggest that patients with severe mental illness have an
      increased prevalence of these risk factors. The causes of increased metabolic and
      cardiovascular risk in this population are strongly related to poverty and
      limited access to medical care, but also to the use of psychotropic medication. A
      review of major published consensus guidelines for metabolic monitoring of
      patients treated with antipsychotic medication that have recommended stringent
      monitoring of metabolic status and cardiovascular risk factors in psychiatric
      patients receiving antipsychotic drugs. There have been six attempts, all
      published between 2004 and 2005: Mount Sinai, Australia, ADA-APA, Belgium, United
      Kingdom, Canada. Each guideline had specific, somewhat discordant,
      recommendations about which patients and drugs should be monitored. However,
      there was agreement on the importance of baseline monitoring and follow-up for
      the first three to four months of treatment, with subsequent ongoing
      reevaluation. There was agreement on the utility of the following tests and
      measures: weight and height, waist circumference, blood pressure, fasting plasma
      glucose, fasting lipid profile. In the second part, the French experts propose
      guidelines for practising psychiatrists when initiating and maintaining therapy
      with antipsychotic drugs: the first goal is identification of risk factors for
      development of metabolic and cardiovascular disorders: non modifiable risk
      factors: these include: increasing age, gender (increased rates of obesity,
      diabetes and metabolic syndrome are observed in female patients treated with
      antipsychotic drugs), personal and family history of obesity, diabetes, heart
      disease, ethnicity as we know that there are increased rates of diabetes,
      metabolic syndrome and coronary heart disease in patients of non European
      ethnicity, especially among South Asian, Hispanic, and Native American people.
      Modifiable risk factors: these include: obesity, visceral obesity, smoking,
      physical inactivity, and bad diet habits. Then the expert's panel focussed on all
      the components of the initial visit such as: family and medical history; baseline
      weight and BMI should be measured for all patients. Body mass index can be
      calculated by dividing weight (in kilograms) by height (in meters) squared;
      visceral obesity measured by waist circumference; blood pressure; fasting plasma
      glucose; fasting lipid profiles. These are the basic measures and laboratory
      examinations to do when initiating an antipsychotic treatment. ECG: several of
      the antipsychotic medications, typical and atypical, have been shown to prolong
      the QTc interval on the ECG. Prolongation of the QTc interval is of potential
      concern since the patient may be at risk for wave burst arrhythmia, a potentially
      serious ventricular arrhythmia. A QTc interval greater than 500 ms places the
      patient at a significantly increased risk for serious arrhythmia. QTc
      prolongation has been reported with varying incidence and degrees of severity.
      The atypical antipsychotics can also cause other cardiovascular adverse effects
      with, for example, orthostatic hypotension. Risk factors for cardiovascular
      adverse effects with antipsychotics include: known cardiovascular disease,
      electrolyte disorders, such as hypokaliemia, hypomagnesaemia, genetic
      characteristics, increasing age, female gender, autonomic dysfunction, high doses
      of antipsychotics, the use of interacting drugs, and psychiatric illness itself.
      In any patient with pre-existing cardiac disease, a pre-treatment ECG with
      routine follow-up is recommended. CONCLUDING REMARKS: Patients on antipsychotic
      drugs should undergo regular testing of blood sugar, lipid profile, as well as
      body weight, waist circumference and blood pressure, with recommended time
      intervals between measures. Clinicians should track the effects of treatment on
      physical and biological parameters, and should facilitate access to appropriate
      medical care. In order to prevent or limit possible side effects, information
      must be given to the patient and his family on the cardiovascular and metabolic
      risks. The cost-effectiveness of implementing these recommendations is
      considerable: the costs of laboratory tests and additional equipment costs (such
      as scales, tape measures, and blood pressure devices) are modest. The issue of
      responsibility for monitoring for metabolic abnormalities is much debated.
      However, with the prescription of antipsychotic drugs comes the responsibility
      for monitoring potential drug-induced metabolic abnormalities. The onset of
      metabolic disorders will imply specific treatments. A coordinated action of
      psychiatrists, general practitioners, endocrinologists, cardiologists, nurses,
      dieticians, and of the family is certainly a key determinant to ensure the
      optimal care of these patients.

PMID- 19748370
TI  - [Repetitive and restricted behaviours (RRB) in autism: clinical evaluation].
AB  - INTRODUCTION: Restricted and repetitive behaviours (RRB) represent a common
      problem throughout the autistic spectrum. They comprise a wide range of
      behavioural manifestations that persist over time and resist therapeutics.
      Furthermore, degrees of heterogeneity have been reported in the clinical
      expression of autistic syndrome, particularly in the restricted and repetitive
      aspects. Advances are needed in the understanding of this complex and
      heterogeneous clinical dimension of autism to improve efficacy of therapeutics.
      LITERATURE FINDINGS: Most clinical studies have subdivided RRB into "lower-level"
      sensory-motor behaviours and "higher-level" behaviours, which are more complex
      and characteristic features of autism. However, none of these studies have taken
      into account all the forms of RRB. To date, there is no specific and thorough
      tool to evaluate this dimension of autism. From the analysis of the literature,
      we proposed a list of 43 behaviours covering the full range of repetitive,
      restricted and stereotyped activities observed in autism. AIM OF THE STUDY: The
      aim of the present study was to test the relevance of these 43 RRB in a family
      context. CLINICAL SETTINGS: The participants were 14 children with an autism
      spectrum disorder, aged from six to 16 years. Circumscribed interests were the
      most commonly reported RRB, and motor stereotypies, aggressive and body-focused
      behaviours were the least expressed behaviours. RESULTS: Multivariate statistical
      analysis identified three groups of children with different behavioural profiles
      and three clusters of RRB, i.e. repetitive motor behaviours, repetitive sensory
      vocal behaviours and restricted ideational behaviours. DISCUSSION: Although these
      preliminary results need to be validated in a wider population, the list of 43
      RRB allowed us to describe accurately this symptomatology of autism and to
      confirm the heterogeneity of this dimension of autistic disorders. The
      identification of clinical subgroups, possibly underlain by different
      psychopathological or physiopathological factors would help research and
      contribute to the development of specific new therapeutic strategies which are
      still needed to improve quality of life of patients with autistic disorder and
      their families.

PMID- 19748371
TI  - [Schizophrenia and violence, incidence and risk factors: a Tunisian sample].
AB  - INTRODUCTION: Schizophrenia appears to be the mental pathology the most
      associated with violence. The aim of this study is to show the incidence and the
      different risk factors of violence among schizophrenics. MATERIAL AND METHOD: We
      have compared a group of 30 violent schizophrenic inpatients with another group
      of 30 nonviolent schizophrenic inpatients hospitalised during the same period.
      These two groups have been matched according to age and gender. The comparison
      concerned: sociodemographic parameters, family and personal psychiatric history,
      legal antecedents, social insertion, clinic, Clinical Global Impressions (CGI),
      Global Impairment Scale (GIS) and Positive And Negative Syndrome Scale (PANSS)
      scores for admissions, familial support and insight, compliance to treatment,
      administered treatments, and awareness degree. RESULTS: Violent schizophrenics
      represent 18.07% of all hospitalisations and 26.08% of schizophrenic patients.
      When compared to violent schizophrenic patients, nonviolent schizophrenic
      patients have a better socioeconomic level (77% versus 43%), better professional
      adaptation (67% versus 10%) and familial support (60% versus 10%), better insight
      (87% versus 23%) and therapeutic control (70% versus 17%). Differences are
      significant. We found significantly more personal antecedents of inflicted
      violence within violent schizophrenics (50% versus 13%), more addictive behavior
      (53% versus 13%), and more paranoid and indifferentiated forms (87% versus 47%)
      than in nonviolent schizophrenics. The average of CGI scores was significantly
      higher within violent schizophrenics (5.27+/-0.8 versus 3.77+/-0.5). Conversely,
      the average of EGF scores was lowest (37.6+/-6.5 versus 47.8+/-5.6). The
      comparison of PANSS scores revealed that violent schizophrenic subjects are
      characterised by the existence of more positive signs and more general symptoms
      (34.4+/-4.7 versus 20.2+/-4.5; 55.1+/-11.4 versus 46.1+/-6.9). Violent
      schizophrenics are characterised by higher neuroleptic doses (2375+/-738 mg/d
      versus 1610+/-434 mg/d). Differences here are also significant. DISCUSSION:
      Addictive behaviour seems to considerably increase the risk of turning to
      violence. Thus in our study, 53% of violent patients showed an addictive
      behaviour. These results have also been reported by other authors. It is obvious
      that alcohol and drug abuse double the risk of violence among schizophrenic
      subjects. Psychotic decompensation and rich symptomatology increase the violent
      potential among the schizophrenics. In our study, the PANSS scores were higher
      among violent subjects. Nonviolent schizophrenic subjects have a lesser
      symptomatology of psychiatric disorders and a better outcome as shown by the CGI
      and EGF scores. In our study, the group of violent subjects needed higher
      neuroleptic doses and were noncompliant. Compliance permits the acquisition, and
      then maintains, the stability of the mental status and plays an essential role in
      decreasing dangerousness. In fact, violent schizophrenics exhibit low insight,
      implying diminished awareness of the legal implications of their acts, and are
      little aware of their illness and its dangerousness. In our study, we noted
      better familial support among nonviolent subjects. According to the literature,
      violent schizophrenics are characterised by a particularly hostile and rejecting
      familial environment. CONCLUSION: Awareness of these factors will allow us to
      provide improved prevention of violence within schizophrenic subjects.

PMID- 19748372
TI  - [Learning potential and cognitive remediation in schizophrenia].
AB  - BACKGROUND: Many studies have stressed the importance of neurocognitive deficits
      in schizophrenia that represent a core feature of the pathology. Cognitive
      dysfunctions are present in 80% of schizophrenic patients, including deficits in
      attention, memory, speed processing and executive functioning, with well-known
      functional consequences on daily life, social functioning and rehabilitation
      outcome. Recent studies have stressed that cognitive deficits, rather than the
      positive or negative symptoms of schizophrenia, predict poor performance in basic
      activities of daily living. If it is possible to reduce psychotic symptoms and to
      prevent relapses with antipsychotic medication, it is not yet possible to have
      the same convincing impact on cognitive or functional impairments. Cognitive
      remediation is a new psychological treatment which has proved its efficacy in
      reducing cognitive deficits. A growing literature on cognitive rehabilitation
      suggests possibilities that in schizophrenia, specific techniques are able to
      enhance an individual's cognitive functioning. LITERATURE FINDINGS: Presently,
      two distinct and complementary cognitive remediation methods have been developed:
      the compensatory and the restorative approaches: (A) restorative approaches
      attempt to improve function by recruiting relatively intact cognitive processes
      to fill the role of those impaired, or by using prosthetic aids to compensate for
      the loss of function; (B) in contrast, in the restorative approach cognitive
      deficits are targeted directly through repeated practice training. However,
      results concerning cognitive remediation remain inconsistent. It is clear that
      not all individuals with schizophrenia display cognitive impairment, and even
      among those who do, the specific pattern of cognitive functioning varies.
      Moreover, traditional neurocognitive assessment, with a single or static
      administration of cognitive measures, provides moderately good prediction of
      skills acquisition in schizophrenia. Among other factors such as motivation,
      awareness of having a disease and acuteness of symptomatology, some studies have
      exposed that a cognitive variable, learning potential could mediate in part the
      effectiveness of cognitive remediation. DISCUSSION: The concept of learning
      potential is used to explain some of the observed variability in cognitive
      functioning. Learning potential is the ability to attain and utilize cognitive
      skills after cognitive training: it is assessed by individual variation in
      performance across three consecutive administrations of the Wisconsin Card
      Sorting Test (WCST): a pretest with standard instruction procedures, a training
      phase with expanded instruction and a post test with only standard instruction.
      Three learner subtypes can be identified: "learners" who perform poorly at the
      pretest but improve performance during the post-test, "non-retainers" who perform
      poorly at pre-test and do not improve at post-testing and "high achievers" who
      perform well in the initial pretest and maintain their good performance across
      the other two administrations. The assessment of learning potential could
      predict, with other psychological measures such as insight and motivation, the
      most effective neurocognitive rehabilitation program for an individual patient,
      and could help the clinician to optimize patient outcome through appropriate
      individual management. CONCLUSION: Indeed, learning potential could represent a
      good cognitive predictor and indicator for rehabilitation in schizophrenia for
      clinicians and should be used in cognitive assessment practice. However, the
      individuals most likely to benefit from cognitive remediation, and whether
      changes in cognitive function translate into functional improvements, are as yet
      unclear.

PMID- 19748373
TI  - [Depression and frontal dysfunction: risks for the elderly?].
AB  - BACKGROUND: Frontal lobe syndromes include reduced activity, particularly a
      diminution of spontaneous activity, lack of drive, inability to plan ahead, and
      induce a lack of concern. These last points constitute the executive dysfunction
      syndrome. That executive dysfunction could be the core defect in patients with
      geriatric or vascular depression, and might be related to frontal-subcortical
      circuit dysfunction. Sometimes frontal lobe syndromes are associated with
      restless, aimless, uncoordinated behavior or even disinhibition, increasing the
      risks of falls and of malnutrition. Some authors have distinguished between
      lesions of the lateral frontal cortex, most closely linked to the motor
      structures of the brain, which lead to disturbances of movement and action with
      perseveration and inertia, and lesions of the orbital and medial areas,
      interlinked with limbic and reticular systems, damage to which leads to
      disinhibition and changes of affect. The medial frontal syndrome is marked by
      akinesia, associated with gait disturbances, and loss of autonomy. For these
      reasons, it has been proposed that a subtype of depression, "depression-executive
      dysfunction syndrome" could occur in late life. This assertion was based on
      clinical, neuropathological, and neuroimaging findings suggesting that
      frontostriatal dysfunctions contribute to the development of both depression and
      executive dysfunction and influence the course of depression. Depressive
      symptomatology, and especially psychomotor retardation and loss of interest in
      activities, contributed to disability in depression-executive dysfunction
      syndrome patients. This study is not restricted to major depression. It examined
      the relationship of executive impairment to the course of depressive symptoms
      among a psychogeriatric population with dementia or depression in order to assess
      the consequences of these pathologies on disabilities of aged persons. METHODS:
      The study was carried out in Limoges (France) during 2006 and 2007. Three hundred
      and twenty one psychogeriatric outpatients were included after their written
      agreement. They were assessed using different scales for autonomy, cognition,
      depression, frontal impairment and these results were compared with the risk of
      fall, a possible loss of autonomy and a proteino-energical malnutrition. The
      statistical study was made using the Systat 11 software. The following tests were
      used: Student Test, Chi(2) test, and the Manova test, which was adjusted to the
      duration of the disease, the caregiver's age, his/her education level, and level
      of cognitive impairment. The regression method used was the multiple linear
      regression method as well as a descending step-by-step analysis. RESULTS: One
      hundred and thirty six males (77.3+/-7.09 years old) and 185 females (80.4+/-6.5
      years old) were recruited. Patients mainly presented with Alzheimer's disease
      (n=123) and 65 presented an associated depression, 25 presented vascular
      dementia, 30 a Lewy bodies dementia, 27 a fronto-temporal dementia. Twenty-seven
      presented psychosis and 40 a Mild Cognitive Impairment. A control group was
      composed of 33 persons presumed without psychogeriatric pathologies. Depression
      associated with an executive dysfunction syndrome increased loss of autonomy, the
      risk of fall and of malnutrition, especially in the case of cognitive impairment.
      The multivariate regression analysis step-by-step shows an increasing risk of
      fall in the presence of a depression-executive dysfunction syndrome. Motivation
      is altered when the patient is depressed. In demented patients, depression
      significantly increases behavioral disorders, social and familial relationships,
      and instrumental acts of daily life. It precipitates the risks of falls and of
      malnutrition. DISCUSSION: The principal finding of this study is that geriatric
      depression is characterized by impaired executive functioning. In the present
      study, depressed patients also had a greater tendency to fall and to suffer from
      malnutrition. Executive processes are fundamental to the daily functioning of
      depressed older adults, and dysfunction may lead to a lack of compensatory
      strategies that would improve the outcomes of late-life depression or of
      increasing dependency as well. In demented patients, depression triggers loss of
      motivation and executive dysfunction as well. CONCLUSIONS: Depression and
      executive dysfunction triggers the loss of autonomy, the risk of fall and of
      malnutrition in elderly patients. The clinical significance of this study is that
      the delineation of specific executive in depressed elderly patients may
      facilitate the development of effective treatment interventions, including
      treatment for geriatric depression.

PMID- 19748374
TI  - [Pharmaco-therapeutic evaluation of medical treatments of adult autistics and
      multi-handicapped patients in a public mental health unit].
AB  - INTRODUCTION: This paper presents a survey conducted on a population of multi
      handicapped patients and autistic adults hospitalised long term in the Paul
      Guiraud mental health Hospital in Villejuif France. OBJECTIVE: The aim of the
      survey is to deepen the knowledge of the treatments for this specific population.
      METHODS: A preliminary medical investigation was conducted on the population in
      order to target different groups of patients. Once patients had listed and
      defined their medical needs, prescriptions were analysed to assess whether
      clinical characteristics had an impact. Thus, the analysis of treatments was
      carried out for the 57 patients (14% of the hospital population) and compared to
      other investigations conducted on the population commonly hospitalised in
      Psychiatry. The evaluation of the treatments was obtained through a questionnaire
      which enabled us to target the therapeutical goals and to obtain additional
      clinical information. The drugs with a high rate of prescription were compared
      between the autistic group and the multi-handicapped group. The important
      comorbidity and the multi-symptomatology of autism often involves the
      polymedication of these patients (8+/-0.8 drugs per patient). RESULTS: Fifty per
      cent of the treatments are referred to as somatic treatments. The average length
      of stay (22.3 years) and the high average age are aggravating factors for
      polymedication. The average number of psychotropic molecules also appears higher
      than in the populations studied in the literature. The heterogeneity of clinical
      forms of autism and polyhandicap encourages prescribers to multidrug therapy. The
      prescriptions usually remain stable (17.5% of psychiatric treatment is adapted
      and only 7% of somatic treatment). Epilepsy and constipation are the main treated
      somatic disorders. In psychiatry, the oral route is the privileged route of
      administration (81% of treatments) with, more specifically, the use of drinkable
      solutions for the psychiatric treatment. Neuroleptic drugs are the basic
      treatment of these patients (82% of prescriptions). The aim of the prescription
      of neuroleptics is essentially to obtain behavioural or antipsychotic sedation.
      Cyamemazin is the most prescribed drug (46% of neuroleptic prescriptions), mainly
      for its anxiolytic effects. Co-prescription is frequent (55.3%) and corresponds
      to 53% of co-prescriptions of an association of phenothiazine and butyrophenone.
      Doses are high, which implies the prescription of treatments against the
      neuroleptics side-effects (86% of patients have such a prescription). The rate of
      prescriptions of the other psychotropic drugs (hypnotics, anxiolytics, etc.) is
      approximately equivalent between our population and the "classical" hospitalised
      psychiatric population, except for antidepressants (7% of prescriptions) because
      the differential diagnosis is difficult in these patients. Nearly 60% of patients
      have prescriptions of hypnotic drugs. However, this figure is tempered by
      prescriptions of drugs "if necessary" in two-thirds of the cases. Finally, only
      30% of patients have systematic hypnotic prescriptions. CONCLUSION: Although
      autistics are clinically different from multi-handicapped patients, no
      statistically significant difference was demonstrated in their prescriptions,
      which implies a similar pharmacological management. It is difficult to clearly
      distinguish these two populations only according to the type of drugs used and
      the doses prescribed.

PMID- 19748375
TI  - [Cannabis and psychosis: search of a causal link through a critical and
      systematic review].
AB  - INTRODUCTION: Although cannabis use may be involved in the aetiology of acute
      psychosis, there has been considerable debate about the association observed
      between cannabis use and chronic psychosis. In particular, because of the
      frequent co-occurrence between schizophrenia and cannabis use, the question has
      been raised of a causal link between exposure to cannabis as a risk factor and
      the development of psychosis or psychotic symptoms. OBJECTIVE: The aim of this
      article was to examine the evidence that cannabis use causes chronic psychotic
      disorders by using established criteria of causality. These criteria were defined
      by: biologic plausibility, strength of the interaction between the risk factor
      and the disease, reprieability of the results, temporal sequence between the
      exposure to the risk factor and the beginning of the disease and existence of a
      dose-effect relationship. METHODS: The selected studies were found in Medline
      using the keywords "cannabis" and "psychosis", "cannabis" and "schizophrenia",
      "cannabis" and "psychotic symptoms" and "prospective" or "cohort" or
      "longitudinal". The selected studies were all prospective studies assessing the
      temporal sequence between cannabis use and emergence of psychosis or psychotic
      symptoms. The search strategies resulted in 60 records that were screened by
      reading both titles and abstracts. Seventeen studies were considered eligible,
      and then, after reading the full text, seven met the inclusion criteria. RESULTS:
      Together, the seven studies were all prospective cohorts and represented 50,275
      human subjects. There were three European studies (from Sweden, Holland and
      Germany), one from New Zealand and one from Australia. Only one study of the
      seven did not show a significant association between cannabis consumption and
      increase of the risk of developing a psychosis. However, this study had some
      bias, such as low level of cannabis use and the lack of evaluation of cannabis
      use after inclusion. For the six other studies, data show the existence of a
      significant association between cannabis use and psychotic disorders (with an
      increased risk between 1.2 and 2.8 in Zammit et al.'s study), particularly among
      vulnerable individuals (that is with a prepsychotic state at the time of
      inclusion). Therefore, all the studies that assessed a dose-effect relationship
      showed this link between cannabis use and the emergence of psychosis or psychotic
      symptoms. The fact that all causal criteria were present in the studies suggests
      that cannabis use may be an independent risk factor for the development of
      psychosis. Results seem to be more consistent for vulnerable individuals with the
      hypothesis that cannabis use may precipitate psychosis, notably among vulnerable
      subjects. In particular, early onset of cannabis use during adolescence should be
      an environmental stressor that interacts with a genetic predisposition to induce
      a psychotic disorder. CONCLUSION: The objective of this article was to examine
      whether cannabis use can be an independent risk factor for chronic psychotic
      disorders, by using established criteria of causality. Data extracted from the
      selected studies showed that cannabis use may be an independent risk factor for
      the development of psychotic disorders. Early screening of the vulnerability to
      psychotic disorder should permit improved focus on prevention and information
      about the specific risks related to cannabis use among this population.

PMID- 19748376
TI  - [Is late-onset schizophrenia related to neurodegenerative processes? A review of
      literature].
AB  - INTRODUCTION: Since 1943 when, for the first time, M. Bleuler used the term late
      onset schizophrenia (LOS) to refer to diagnostic groups gathering some clinical
      features of schizophrenia, but with onset after the age of 40, opinions on this
      entity are divided. The main question is whether LOS and schizophrenia, with
      onset in early adulthood (early-onset schizophrenia EOS), have the same
      etiopathogeny. This discussion became more complex with the introduction, in
      2000, of a new entity, the "very-late-onset schizophrenia-like psychosis"
      (VLOSP), which took the place of "late paraphrenia" and grouped together
      schizophrenia, delusional disorders and paranoid psychosis with age of onset
      after 60 years. Neuropathological processes underlying these entities have not
      beed determined. In particular, neurodegenerative processes could be explored.
      METHOD: A literature review between 1 January 1995 and 30 April 2008, based on a
      research on PubMed with the terms "late-onset schizophrenia", "paraphrenia",
      "late paraphrenia", "VLOSP", and "late psychosis", takes stock of the various
      studies and hypotheses which have investigated the link between LOS/VLOSP and
      neurodegenerative processes. RESULTS: Clinical approach: there is no greater
      family history of dementia disorders in LOS/VLOSP than in the general population.
      Neuropsychological pattern between LOS and Alzheimer's disease (AD) seems
      different, with more impairment in delayed recall in AD, and in short-term memory
      in LOS. Some longitudinal studies, however, have argued that a part of patients
      with LOS would develop dementia at 10 years. These patients would have a later
      onset of disorders (> 60 years). Anatomopathological approach:
      anatomopathological studies show that LOS is not consecutive to AD, and might be
      related to a restricted limbic tauopathy. Neuroimaging approach: Magnetic
      Resonance Imaging (MRI) morphological neuroimaging studies show little
      differences between LOS and EOS. The thalamus volume was significantly smaller,
      and cortical atrophy was more important in LOS. MRI neuroimaging studies
      regarding white matter hyperintensities (WMH), which are considered as a
      macroscopic manifestation of cerebrovascular disease (CD), show inconsistent
      results. Positive results are observed with LOS subjects with later onset of
      disease. In addition, WMH were not located on cerebral tracts, which are
      implicated in EOS, but were periventricular. DISCUSSION: It is notable that the
      studies conducted do not differentiate between LOS and VLOSP, since these two
      groups of patients are generally mixed. Furthermore, an attempt to analyse the
      data has to take into account only the studies which have included subjects with
      strict criteria of schizophrenia, independently of the disorders' age of onset.
      In addition, we found no study comparing LOS and Lewy Bodies Dementia, which is
      however an important differential diagnosis. The two main hypotheses tested
      appear to be: (1): is LOS a prodrome of AD? (2): is LOS consecutive to CD? This
      review permits a partial answer to these questions. First, LOS as a prodrome of
      AD seems very unlikely, considering anatomopathological studies. However, it is
      possible that subjects with later age of onset of the disease develop dementia at
      10 years. Second, CD seems not to be altered by the cerebral tracts which are
      implicated in EOS. A hypothesis could be that the tracts implicated in LOS and
      EOS differ. This might explain the differences found in clinical (less formal
      thought disorders and negative symptoms in LOS compared with EOS) and
      electroencephalographical studies (no reduction of P300's amplitude in LOS, which
      has however been proposed as trait marker of schizophrenia in EOS) between LOS
      and EOS. These tracts could be related to a limbic tauopathy found in
      anatomopathological studies. More vulnerable subjects would develop LOS with
      ageing. Other subjects would develop LOS secondary to CD. This could explain the
      later age of onset of the disease in these subjects.

PMID- 19748377
TI  - [Schizophrenic patients' length of stay: mental health care implication and
      medicoeconomic consequences].
AB  - A striking reduction in hospital beds can be seen as the defining characteristic
      of mental health services in many western countries during the last 30 years. The
      politic of shortening hospital stays for persons with psychosis has been
      questioned by a number of authors. Studies of patients returning to the community
      compared to those remaining in institutions show not only better quality of life
      and larger friendship networks, but also reductions in dependence on
      pharmacotherapies and lower mortality rates. An interesting comparison between
      three contrasting mental care systems in Holland, Italy and Australia concluded
      not surprisingly that hospital stays are shortest where community care is more
      developed, although long term hospitalization will always be required for a small
      number of very severe patients. The general conclusion was that shorter stays
      work best if and only if there is high quality community care which comes into
      play immediately on discharge. The central issue appears to be that the
      beneficial effects of short stays are modulated by conditions of discharge. That
      is, in the absence of a planned discharge policy, patients appear to be better
      off staying longer, in order that a structured rehabilitation plan may be put in
      place. The process of deinstitutionalisation has been driven by a variety of
      forces. One is to reduce costs, since hospital inpatient costs are very high.
      Generally, between one- and two-thirds of the total health care cost of
      schizophrenia is for hospitalization, even in countries that have already
      substantially reduced their inpatient provision. Recent years have seen a trend
      toward mental health services provided from community-based settings for defined
      catchment areas. The development of these services has a heavy cost, with the
      opening of replacement accommodation and other community facilities and large
      teams. While few patients or clinicians would contest today that a return to
      normal community life is preferable to institutionalization, the adoption of
      shorter hospital stays was not an evidence-based policy and no adequate
      evaluation study was ever put in place to predict the social, clinical and
      economic consequences of this widespread practice.

PMID- 19748378
TI  - [Comment on: "Lack of insight in schizophrenia: a review. Part I: theoretical
      concept, clinical aspects and Amador's model" of S. Raffard, S. Bayard, D.,
      Capdevielle, F. Garcia, J.-P. Boulenger et M.-C. Gely-Nargeot].

PMID- 19748379
TI  - Depression in adults with a chronic physical health problem: treatment and
      management.

PMID- 19748380
TI  - Tomorrow's Doctors: an improvement if evaluated.

PMID- 19748381
TI  - Who should lead WHO EURO?

PMID- 19748382
TI  - Execution of prisoners with mental illnesses in Japan.

PMID- 19748383
TI  - Young people: not as healthy as they seem.

PMID- 19748384
TI  - The deadly toll of S pneumoniae and H influenzae type b.

PMID- 19748385
TI  - Consent for biobank tissue in somatic-cell nuclear transfer.

PMID- 19748386
TI  - Antenatal education programmes: do they work?

PMID- 19748387
TI  - Quarraisha Abdool Karim: investigating HIV/AIDS in South Africa. Interview by
      Priva Shetty.

PMID- 19748388
TI  - The SERPING1 gene and age-related macular degeneration.

PMID- 19748390
TI  - Aspirin in the primary prevention of vascular disease.

PMID- 19748391
TI  - Aspirin in the primary prevention of vascular disease.

PMID- 19748392
TI  - Aspirin in the primary prevention of vascular disease.

PMID- 19748393
TI  - Aspirin in the primary prevention of vascular disease.

PMID- 19748395
TI  - An academia-industry partnership.

PMID- 19748396
TI  - An academia-industry partnership.

PMID- 19748397
TI  - Global patterns of mortality in young people: a systematic analysis of population
      health data.
AB  - BACKGROUND: Pronounced changes in patterns of health take place in adolescence
      and young adulthood, but the effects on mortality patterns worldwide have not
      been reported. We analysed worldwide rates and patterns of mortality between
      early adolescence and young adulthood. METHODS: We obtained data from the 2004
      Global Burden of Disease Study, and used all-cause mortality estimates developed
      for the 2006 World Health Report, with adjustments for revisions in death from
      HIV/AIDS and from war and natural disasters. Data for cause of death were derived
      from national vital registration when available; for other countries we used
      sample registration data, verbal autopsy, and disease surveillance data to model
      causes of death. Worldwide rates and patterns of mortality were investigated by
      WHO region, income status, and cause in age-groups of 10-14 years, 15-19 years,
      and 20-24 years. FINDINGS: 2.6 million deaths occurred in people aged 10-24 years
      in 2004. 2.56 million (97%) of these deaths were in low-income and middle-income
      countries, and almost two thirds (1.67 million) were in sub-Saharan Africa and
      southeast Asia. Pronounced rises in mortality rates were recorded from early
      adolescence (10-14 years) to young adulthood (20-24 years), but reasons varied by
      region and sex. Maternal conditions were a leading cause of female deaths at 15%.
      HIV/AIDS and tuberculosis contributed to 11% of deaths. Traffic accidents were
      the largest cause and accounted for 14% of male and 5% of female deaths. Other
      prominent causes included violence (12% of male deaths) and suicide (6% of all
      deaths). INTERPRETATION: Present global priorities for adolescent health policy,
      which focus on HIV/AIDS and maternal mortality, are an important but insufficient
      response to prevent mortality in an age-group in which more than two in five
      deaths are due to intentional and unintentional injuries. FUNDING: WHO and
      National Health and Medical Research Council.

PMID- 19748398
TI  - Burden of disease caused by Streptococcus pneumoniae in children younger than 5
      years: global estimates.
AB  - BACKGROUND: Streptococcus pneumoniae is a leading cause of bacterial pneumonia,
      meningitis, and sepsis in children worldwide. However, many countries lack
      national estimates of disease burden. Effective interventions are available,
      including pneumococcal conjugate vaccine and case management. To support local
      and global policy decisions on pneumococcal disease prevention and treatment, we
      estimated country-specific incidence of serious cases and deaths in children
      younger than 5 years. METHODS: We measured the burden of pneumococcal pneumonia
      by applying the proportion of pneumonia cases caused by S pneumoniae derived from
      efficacy estimates from vaccine trials to WHO country-specific estimates of all
      cause pneumonia cases and deaths. We also estimated burden of meningitis and non
      pneumonia, non-meningitis invasive disease using disease incidence and case
      fatality data from a systematic literature review. When high-quality data were
      available from a country, these were used for national estimates. Otherwise,
      estimates were based on data from neighbouring countries with similar child
      mortality. Estimates were adjusted for HIV prevalence and access to care and,
      when applicable, use of vaccine against Haemophilus influenzae type b. FINDINGS:
      In 2000, about 14.5 million episodes of serious pneumococcal disease (uncertainty
      range 11.1-18.0 million) were estimated to occur. Pneumococcal disease caused
      about 826,000 deaths (582,000-926,000) in children aged 1-59 months, of which
      91,000 (63,000-102,000) were in HIV-positive and 735,000 (519,000-825,000) in HIV
      negative children. Of the deaths in HIV-negative children, over 61% (449,000
      [316,000-501,000]) occurred in ten African and Asian countries. INTERPRETATION: S
      pneumoniae causes around 11% (8-12%) of all deaths in children aged 1-59 months
      (excluding pneumococcal deaths in HIV-positive children). Achievement of the UN
      Millennium Development Goal 4 for child mortality reduction can be accelerated by
      prevention and treatment of pneumococcal disease, especially in regions of the
      world with the greatest burden. FUNDING: GAVI Alliance and the Vaccine Fund.

PMID- 19748399
TI  - Burden of disease caused by Haemophilus influenzae type b in children younger
      than 5 years: global estimates.
AB  - BACKGROUND: Haemophilus influenzae type b (Hib) is a leading cause of childhood
      bacterial meningitis, pneumonia, and other serious infections. Hib disease can be
      almost completely eliminated through routine vaccination. We assessed the global
      burden of disease to help national policy makers and international donors set
      priorities. METHODS: We did a comprehensive literature search of studies of Hib
      disease incidence, case-fatality ratios, age distribution, syndrome distribution,
      and effect of Hib vaccine. We used vaccine trial data to estimate the proportion
      of pneumonia cases and pneumonia deaths caused by Hib. We applied these
      proportions to WHO country-specific estimates of pneumonia cases and deaths to
      estimate Hib pneumonia burden. We used data from surveillance studies to develop
      estimates of incidence and mortality of Hib meningitis and serious non-pneumonia,
      non-meningitis disease. If available, high-quality data were used for national
      estimates of Hib meningitis and non-pneumonia, non-meningitis disease burden.
      Otherwise, estimates were based on data from other countries matched as closely
      as possible for geographic region and child mortality. Estimates were adjusted
      for HIV prevalence and access to care. Disease burden was estimated for the year
      2000 in children younger than 5 years. FINDINGS: We calculated that Hib caused
      about 8.13 million serious illnesses worldwide in 2000 (uncertainty range 7.33
      13.2 million). We estimated that Hib caused 371,000 deaths (247,000-527,000) in
      children aged 1-59 months, of which 8100 (5600-10,000) were in HIV-positive and
      363,000 (242,000-517,000) in HIV-negative children. INTERPRETATION: Global burden
      of Hib disease is substantial and almost entirely vaccine preventable. Expanded
      use of Hib vaccine could reduce childhood pneumonia and meningitis, and decrease
      child mortality. FUNDING: GAVI Alliance and the Vaccine Fund.

PMID- 19748400
TI  - Poor reception?

PMID- 19748401
TI  - Central sensitization induced in trigeminal and upper cervical dorsal horn
      neurons by noxious stimulation of deep cervical paraspinal tissues in rats with
      minimal surgical trauma.
AB  - OBJECTIVE: This study investigated if central sensitization is induced in the
      trigeminal subnucleus caudalis (also termed the medullary dorsal horn) and C1 and
      C2 dorsal horns by noxious stimulation of deep upper cervical paraspinal tissues
      in a preparation relatively free of surgical trauma. METHODS: Adult male Sprague
      Dawley rats (275-450 g) were anesthetized intraperitoneally. Animals were then
      placed in a stereotaxic frame; a small cutaneous incision was made 3 to 4 mm near
      the bregma in the midline, and an opening into the skull was prepared by a 1/32
      inch drill, 1 mm to the left from the midline. An epoxylite-coated tungsten
      microelectrode was introduced at an 18 degrees angle to enter this small opening
      on the skull and was then carefully advanced about 16 mm through cortex,
      cerebellum, and brainstem to reach subsequently histologically confirmed sites in
      the Vc and upper cervical (C1 and C2) dorsal horn region. Thirty-three, 27, and
      15 neurons recorded in medullary, C1, and C2 dorsal horns, respectively, of
      chloralose/urethane-anesthetized rats were activated by noxious stimulation of
      mechanoreceptive fields involving V1, V2, and/or V3 trigeminal nerve territories.
      The inflammatory irritant mustard oil was injected into the deep paraspinal
      tissues at the level of the left C1-C2 joint. Pre and postinjection receptive
      field (RF) sizes were mapped by nonnoxious mechanical stimuli and noxious
      mechanical and heat stimuli. RESULTS: A 30- to 50-minute increase (mean, 165% +/-
      38.1%) in RF size postinjection for 62% of neurons tested was demonstrated,
      suggesting central sensitization; for most (>70%) neurons, the RF expanded
      caudally into cervically innervated tissues. CONCLUSIONS: These findings provide
      the first documentation that deep cervical nociceptive inputs can induce central
      sensitization in medullary and C1/C2 dorsal horns and suggest that these effects
      may reflect mechanisms contributing to deep cervical pain and its referral.

PMID- 19748402
TI  - Immediate effect of ultrasound and ischemic compression techniques for the
      treatment of trapezius latent myofascial trigger points in healthy subjects: a
      randomized controlled study.
AB  - OBJECTIVE: The purpose of this study was to determine immediate effects of
      ischemic compression (IC) and ultrasound (US) for the treatment of myofascial
      trigger points (MTrPs) in the trapezius muscle. METHODS: Sixty-six volunteers,
      all CEU-Cardenal Herrera University, Valencia, Spain, personnel, participated in
      this study. Subjects were healthy individuals, diagnosed with latent MTrPs in the
      trapezius muscle. Subjects were randomly placed into 3 groups: G1, which received
      IC treatment for MTrPs; G2, which received US; and G3 (control), which received
      sham US. The following data were recorded before and after each treatment: active
      range of motion (AROM) of cervical rachis measured with a cervical range of
      motion instrument, basal electrical activity (BEA) of muscle trapezius measured
      with surface electromyography, and pressure tolerance of MTrP measured with
      visual analogue scale assessing local pain evoked by the application of 2.5
      kg/cm(2) of pressure using a pressure analog algometer. RESULTS: The results
      showed an immediate decrease in BEA of the trapezius muscle and a reduction of
      MTrP sensitivity after treatment with both therapeutic modalities. In the case of
      IC, an improvement of AROM of cervical rachis was also been obtained. CONCLUSION:
      In this group of participants, both treatments were shown to have an immediate
      effect on latent MTrPs. The results show a relation among AROM of cervical
      rachis, BEA of the trapezius muscle, and MTrP sensitivity of the trapezius muscle
      gaining short-term positive effects with use of IC.

PMID- 19748403
TI  - Comparison between elderly and young males' lumbopelvic extensor muscle endurance
      assessed during a clinical isometric back extension test.
AB  - OBJECTIVE: Endurance of the back extensor muscles has become important for
      clinical decisions that guide interventions, particularly for chronic low back
      pain patients. Very little information is available regarding back muscle
      endurance in the elderly. The aim of this study was to investigate back extensor
      muscle endurance in healthy elderly subjects during a modified Sorensen test.
      METHODS: Sixteen elderly and 20 young male adults participated in our cross
      sectional study. The subjects performed a modified Sorensen test (on a 45 degrees
      Roman chair) to quantify lumbopelvic extensor muscle endurance. Pre and
      postfatigue back extension maximal voluntary force was assessed according to an
      isometric lift test in a semicrouched position. Endurance time, perceived
      exertion (Borg CR10 scale), and postfatigue reduction of lifting force were
      recorded and compared among groups. RESULTS: Elderly subjects showed a trend
      toward decreased endurance time compared to young adults, but the difference was
      not significant. Similar perceived exertion and diminished maximal force after
      the fatiguing protocol were observed in both young and elderly subjects. Maximal
      isometric lift force was significantly associated with endurance time in young
      but not in elderly subjects. CONCLUSIONS: Lumbopelvic extensor muscle endurance
      and perceived exertion do not differ between young and healthy elderly
      individuals. However, back muscle endurance seems to be modulated by different
      neurophysiologic factors in the elderly. Normative data on young adults should be
      interpreted with caution in assessing back fitness in elderly subjects.

PMID- 19748404
TI  - Short-term effects of manual therapy on heart rate variability, mood state, and
      pressure pain sensitivity in patients with chronic tension-type headache: a pilot
      study.
AB  - OBJECTIVE: The purpose of this study was to investigate the immediate effects of
      head-neck massage on heart rate variability (HRV), mood states, and pressure pain
      thresholds (PPTs) in patients with chronic tension-type headache (CTTH). METHODS:
      Eleven patients (8 females), between 20 and 68 years old, with CTTH participated
      in this crossover study. Patients received either the experimental treatment
      (massage protocol) or a placebo intervention (detuned ultrasound). Holter
      electrocardiogram recordings (standard deviation of the normal-to-normal
      interval, square root of mean squared differences of successive NN intervals,
      index HRV, low-frequency component, and high-frequency component), PPT over both
      temporalis muscles, and Profile of Mood States questionnaire (tension-anxiety,
      depression-dejection, anger-hostility, vigor, fatigue, confusion) were obtained
      preintervention, immediately after intervention, and 24 hours postintervention.
      Self-reported head pain was also collected preintervention and 24 hours
      postintervention. Separate analyses of covariance (ANCOVAs) were performed with
      each dependent variable. The hypothesis of interest was group x time interaction.
      RESULTS: The ANCOVA showed a significant group x time interaction for index HRV
      (F = 4.5, P = .04), but not for standard deviation of the normal-to-normal
      interval (F = 1.1, P = .3), square root of mean squared differences of successive
      NN intervals (F = 0.9, P = .3), low-frequency component (F = 0.03, P = .8), or
      high-frequency component (F = 0.4, P = .5) domains. Pairwise comparisons found
      that after the manual therapy intervention, patients showed an increase in the
      index HRV (P = .01) domain, whereas no changes were found after the placebo
      intervention (P = .7). The ANCOVA also found a significant group x time
      interaction for tension-anxiety (F = 5.3, P = .03) and anger-hostility (F = 4.6,
      P = .04) subscales. Pairwise comparisons found that after the manual therapy
      intervention, patients showed a decrease in tension-anxiety (P = .002) and anger
      hostility (P = .04) subscales, whereas no changes were found after the placebo
      intervention (P > .5 both subscales). No significant changes were found in PPT
      levels (right F = 0.3, P = .6, left F = 0.4, P = .5). A significant group x time
      interaction for pain (F = 4.8, P = .04) was identified. No influence of sex was
      found (F = 1.5, P = .3). Pairwise comparisons showed that head pain (numerical
      pain rating scale) decreased 24 hours after manual therapy (P < .05) but not
      after the placebo intervention (P = .9). CONCLUSIONS: The application of a single
      session of manual therapy program produces an immediate increase of index HRV and
      a decrease in tension, anger status, and perceived pain in patients with CTTH.

PMID- 19748405
TI  - A feasibility study comparing two chiropractic protocols in the treatment of
      patellofemoral pain syndrome.
AB  - OBJECTIVE: The purpose of this pilot study was to determine the feasibility of
      (1) using the existing clinic, clinicians, interns, faculty, and staff from our
      college in conducting all components of a planned randomized controlled clinical
      trial; (2) successfully recruiting patients with patellofemoral pain syndrome
      (PFPS); and (3) consistently, effectively, and safely implementing the study
      protocols and therapy. METHODS: Diagnostic, treatment, and blind assessment
      procedures were carried out while recruitment and administrative techniques for
      managing long-term storage of data and files were developed. Thirty-one patients
      were randomized into a local manipulative group (group A) or to a full kinetic
      chain manipulative therapy group (group B), each combined with exercise and soft
      tissue treatment. The Anterior Knee Pain Scale, visual analog scale, and Patient
      Satisfaction Scale were used. RESULTS: All phases of the feasibility study
      including use of the clinic, staff, recruitment techniques, treatment protocols,
      data collection, input, and analysis were effectively and safely carried out.
      CONCLUSIONS: A feasibility study investigating the ability to conduct a
      randomized controlled trial of a manipulative therapy protocol for PFPS using
      available chiropractic college infrastructure was accomplished. A fully powered
      PFPS trial is feasible and merited.

PMID- 19748406
TI  - Motion palpation used as a postmanipulation assessment tool for monitoring end
      feel improvement: a randomized controlled trial of test responsiveness.
AB  - OBJECTIVE: A tenet of motion palpation theory is the ability to confirm
      postadjustive segmental end-feel improvement (EFI). Only one previous trial has
      evaluated the responsiveness of EFI; this was a study of the thoracic spine. The
      purpose of this study was to evaluate the responsiveness of postadjustive end
      feel for evaluating improvement in putative segmental spinal motion restriction
      after spinal manipulative therapy (SMT) of the cervical spine. METHODS: A
      prospective, blinded, randomized placebo-controlled pilot trial was conducted
      with 20 symptomatic and 10 asymptomatic participants recruited from a
      chiropractic teaching clinic. The treatment group received SMT, and the control
      group received placebo detuned ultrasound. Responsiveness was evaluated as the
      etiologic fraction (% of cases with EFI attributable to SMT) and as the
      sensitivity and specificity of change. RESULTS: For the entire sample, the
      etiologic fraction was 63% (P = .002), sensitivity was 93%, and specificity was
      67%. For symptomatic participants, a strong relationship appeared to exist
      between receiving SMT and EFI (etiologic fraction = 78%, P = .006; sensitivity =
      90%; specificity = 80%). A strong relationship was not found for asymptomatic
      participants (etiologic fraction = 40%, P = .444; sensitivity = 100%; specificity
      = 40%), where EFI was recorded frequently, whether participants received SMT or
      detuned ultrasound. CONCLUSION: The findings of this study showed that motion
      palpation of end-feel assessment appears to be a responsive postmanipulation
      assessment tool in the cervical spine for determining whether perceived motion
      restriction found before treatment improves after SMT. This observation may be
      limited to symptomatic participants.

PMID- 19748407
TI  - The McKenzie classification system in the extremities: a reliability study using
      Mckenzie assessment forms and experienced clinicians.
AB  - OBJECTIVE: This study investigated the reliability of experienced
      physiotherapists in classifying patients in McKenzie nonspecific mechanical
      syndromes from extremity McKenzie assessment forms. METHODS: Real patient
      vignettes (N = 25) were collected during clinical practice; all identifying
      information was removed to make the assessment form anonymous, and the mechanical
      classification chosen by the treating therapist was also deleted. The forms were
      saved in an electronic format. Forms and a sheet to be filled in for
      classification for each vignette and demographic details were sent electronically
      to McKenzie Institute International Diploma holders worldwide. Three repeat
      mailings were undertaken to maximize response rates. RESULTS: Of a sample frame
      of 126 therapists, 97 responded and provided classification for the patient
      vignettes. Overall agreement was 92% and the kappa value was 0.83. CONCLUSION:
      This reliability analysis of McKenzie extremity assessment forms showed a good
      level of reliability among the participating experienced therapists.

PMID- 19748408
TI  - Normative cross-sectional area of the brachial plexus and subclavian artery using
      ultrasonography.
AB  - OBJECTIVE: Ultrasonography has been used to measure the cross-sectional area
      (CSA) of peripheral nerves, but the CSA of the brachial plexus has not previously
      been reported. The purpose of this study was to establish a reference range of
      values for the CSA of the brachial plexus, subclavian artery, and peak systolic
      velocity (PSV) of the subclavian artery in healthy subjects using
      ultrasonography. METHODS: Thirty-two asymptomatic subjects (19 men, 13 women)
      from a chiropractic college with an average age of 29.5 +/- 9.6 participated in
      the study. The brachial plexus and subclavian artery CSA were measured at 3
      locations: interscalene, first rib, and infraclavicular. The PSV of the
      subclavian artery was measured in both supraclavicular and infraclavicular
      locations. Each subject was imaged bilaterally. Means and 95% confidence
      intervals were calculated. Interexaminer reliability was evaluated between 2
      examiners on 15 randomly selected subjects. RESULTS: The average CSA for the
      brachial plexus at the interscalene space, first rib, and infraclavicular
      location was 0.75 +/- 0.05, 0.96 +/- 0.07, and 0.98 +/- 0.07 cm(2), respectively.
      The average CSA for the subclavian artery at the same locations was 0.35 +/-
      0.03, 0.38 +/- 0.03, 0.35 +/- 0.03 cm(2), respectively. The average subclavian
      artery PSV in supraclavicular and infraclavicular locations was 98 +/- 8 and 93
      +/- 7 cm/s, respectively. The overall interexaminer reliability was poor at 0.39
      (0.20-0.55). CONCLUSIONS: This is the first study to obtain normative CSA
      measurements of the brachial plexus and subclavian artery in multiple locations
      of the thoracic outlet as well as interexaminer reliability data. These data may
      be beneficial in future studies designed to assess the brachial plexus and
      subclavian artery in patients with thoracic outlet syndrome.

PMID- 19748409
TI  - Combined multimodal therapies for chronic tennis elbow: pilot study to test
      protocols for a randomized clinical trial.
AB  - OBJECTIVE: The objective of this project was to develop and test protocols for a
      randomized clinical trial (RCT) of 2 multimodal package therapies for chronic
      lateral epicondylitis. METHODS: Six participants were enrolled after case review
      and randomized to 1 of 2 groups (4 in group A and 2 in group B). Group A had high
      velocity low-amplitude manipulation, high-voltage pulse galvanic stimulation,
      counterforce bracing, ice, and exercises, whereas group B had ultrasound,
      counterforce bracing, and exercise. Both groups had 12 weeks of active care and
      instructed to restrict usage of the affected elbow. Participants filled out a
      visual analog scale and the Patient Rated Tennis Elbow Evaluation every week. The
      pain-free grip strength test was measured at baseline, and at the end of the
      third, sixth, ninth, and twelfth visits. RESULTS: One participant in group A
      dropped out before the end of care. Both groups demonstrated changes in all of
      the outcome variables from the baseline to the end point (12 weeks) of treatment.
      Sample size for a larger future randomized clinical trial was calculated as n =
      246 participants. CONCLUSION: The pilot study demonstrated that the study design
      is feasible and that patients could be recruited for a 12-week trial of
      multimodal treatment. A larger trial is warranted in a multicenter setting to
      detect differences in the effects of these treatment strategies.

PMID- 19748410
TI  - Reduction in high blood tumor necrosis factor-alpha levels after manipulative
      therapy in 2 cervicogenic headache patients.
AB  - OBJECTIVE: This case report discusses the treatment of 2 patients with
      cervicogenic headache (CHA) attending the Outpatient Clinic of the Hungarian
      National Institute for Rheumatology and Physiotherapy (Budapest, Hungary) and
      reviews the pathophysiology, therapeutic strategy, and problems associated with
      the treatment of CHA. CLINICAL FEATURES: Patient 1 was a 27-year-old female who
      sustained a whiplash injury. A sharp, shooting headache developed, readily
      induced, and aggravated by just bending the neck backward or by turning her head.
      Magnetic resonance imaging revealed a disk protrusion at C4-C5 pressing the
      anterior cerebrospinal space. Patient 2 was a 62-year-old female who sustained a
      whiplash injury; her cervical movements became restricted, which precipitated
      headaches. Magnetic resonance imaging revealed a paramedian disk hernia between
      the C4 and C5 vertebrae that intruded into the right ventral cerebrospinal space.
      INTERVENTION AND OUTCOME: After 4 weeks of manipulative therapy for patient 1,
      both active and passive range of motion returned to normal, and the high tumor
      necrosis factor-alpha (TNF-alpha) level (63 pg/mL) was substantially reduced (28
      pg/mL). Patient 2 was started on manipulative therapy twice a week for 4 weeks;
      after 2 months, the patient became symptom-free, and high TNF-alpha level (72
      pg/mL) was reduced greatly (35 pg/mL). CONCLUSION: Two patients with whiplash
      injury and disk herniation developed CHA associated with very high TNF-alpha
      levels. After manipulative therapy, these patients became symptom-free, and their
      TNF-alpha levels decreased substantially.

PMID- 19748411
TI  - A noncontiguous 2-level spinal injury in a young female driver due to a 3-point
      seat belt restraint.
AB  - OBJECTIVES: The purpose of this case is to describe noncontiguous fracture and
      dislocations of the thoracolumbosacral spine in a 23-year-old female driver with
      a 3-point seat belt restraint. CLINICAL FEATURES: A 23-year-old woman presented
      to us after a motor vehicle accident while driving with a 3-point seat belt
      restraint. She was neurologically intact except for loss of motor function in the
      distribution of the L5 nerve root in the right lower limb. Computed tomography
      and magnetic resonance imaging showed fracture and dislocation of T3 with
      considerable retrolisthesis and complete anterolisthesis of L5 over the sacrum.
      INTERVENTION AND OUTCOME: Both fractures were reduced and fixed with bone graft
      and instrumentation. She was discharged a month later without any further
      neurologic deterioration. CONCLUSIONS: To our knowledge, this case is the first
      report in the literature of a seat belt safety restraint causing 2 noncontiguous
      fracture dislocations of the spine. Although the consensus is that seat belts can
      prevent most spine injuries, this case shows that the seat belt can be a
      contributor to spine injury. It shows that the shoulder-lap restraint can act as
      2 fulcrums at the upper and lower bands causing 2 separate fracture dislocations.
      A thorough radiologic evaluation of the spine with respect to the clinical
      findings is mandatory in seat belt-restrained road traffic accidents cases.

PMID- 19748412
TI  - Renal cell carcinoma in a 44-year-old man: an etiology for low back pain.
AB  - OBJECTIVE: The aim of this case study is to describe a patient with low back pain
      due to renal cell carcinoma (RCC). A brief review of RCC, including clinical
      presentation, diagnostic imaging, treatment, and outcomes, is discussed. CLINICAL
      FEATURES: A 44-year-old man presented to a chiropractic clinic with chronic low
      back pain. Lumbar spine radiographs and follow-up computed tomography scan
      revealed renal calcification, which was first thought to be calcified hematoma,
      but later, biopsy confirmed that it was RCC. INTERVENTION AND OUTCOME: A
      nephrectomy was performed. At 7-year follow-up, the patient is healthy.
      CONCLUSION: Renal cell carcinoma is not uncommon, and its varied clinical
      presentation may lead individuals to seek a variety of health care providers.
      Spine practitioners should be aware of the possibility of RCC in the clinical
      presentation of low back pain.

PMID- 19748413
TI  - A randomized controlled trial comparing 2 types of spinal manipulation and
      minimal conservative medical care for adults 55 years and older with subacute or
      chronic low back pain.

PMID- 19748415
TI  - Biochemical and molecular mechanisms of aging: from model systems to human
      longevity. Preface.

PMID- 19748416
TI  - Genetic profiles of Shiga toxin and intimin genes found in stool broth cultures:
      a 2-year reference laboratory study.
AB  - Shiga toxin (Stx)-producing Escherichia coli (STEC) are associated with
      potentially serious illness in humans. STEC detection is often based on the
      presence of Stxs, Stx(1) and/or Stx(2), and intimin, encoded by the eae gene. A 2
      year collection of stool broth cultures was tested for variants of stx(1),
      stx(2), and eae. Approximately 80% (138 of 174) were positive for stx(1) and/or
      stx(2), with stx(1) as the most prevalent (66%). Of the stx(1) variants, stx(1)
      was the most common (76%) followed by stx(1c) (22%). Analysis of stx(2)-positive
      isolates found 20 (53%) stx(2), 13 (34%) stx(2)/stx(2v-ha), 3 (8%) stx(2v-ha), 1
      (3%) stx(2v-hb), and 1 (3%) stx(2d-activatable). Findings of stx(2)/stx(2v-ha)
      and stx(2d-activatable) are noteworthy given associations with hemolytic uremic
      syndrome and increased cytotoxicity, respectively. Of the Stx positive, 94 (68%)
      were eae positive with 31 (33%) eae(varepsilon1), 19 (20%) eae(gamma1), and 18
      (19%) eae(beta1). A predominance of eae(varepsilon1) may suggest a new pathogenic
      significance because, reportedly, eae(beta1) is one of the most widespread
      variants.

PMID- 19748417
TI  - Determination of new cutoff values for indirect immunofluorescence antibody test
      for Q fever diagnosis in Denmark.
AB  - Q fever is a ubiquitous zoonosis caused by Coxiella burnetii. The disease is
      emerging in many parts of the world, likely because of increased awareness and
      availability of better diagnostics. The diagnosis is primarily based on serology.
      Because the prevalence of the disease varies worldwide, the establishment of
      local cutoff values is needed. A baseline for antibodies against C. burnetii in
      Denmark was defined by testing sera from healthy Danish volunteers using a
      commercially available immunofluorescence antibody test. Cross-reactivity was
      studied on sera obtained from patients experiencing clinically related diseases.
      The cutoff titers suggested by the manufacturer were found to result in very low
      specificity of the test. The specificity was, however, effectively increased by
      using cutoff titers based on the local baseline and equal to immunoglobulin M
      (IgM) phase I > or =128, IgM phase II > or =256, IgG phase I > or =512, and IgG
      phase II > or =1024.

PMID- 19748418
TI  - Performance characteristics of the Euroimmun enzyme-linked immunosorbent assay
      kits for Brucella IgG and IgM.
AB  - Brucella IgG and IgM ELISA kits manufactured by Euroimmun (Lubeck, Germany) were
      evaluated in a reference laboratory setting. Intraassay coefficient of variation
      (CV) values were < or =10% for positive sera and < or =12% for negative sera;
      interassay CVs were < or =12% for positive sera and < or =20% for negative sera.
      The tube agglutination test (TAT) was performed on 51 sera exhibiting various
      ELISA reactivity profiles. All 18 sera negative for both IgG and IgM by ELISA
      were TAT negative (titer <1:80), whereas 31 (94%) of 33 sera positive for IgG
      and/or IgM were TAT positive; the 2 discordant sera were IgG positive IgM
      negative by ELISA. None of 41 sera from healthy laboratory employees were ELISA
      IgG positive, whereas 1 (2%) of 41 was ELISA IgM positive. Similarly, 0 of 149
      potentially cross-reactive sera (containing rheumatoid factor or antibodies to
      selected Gram-negative bacteria) was ELISA IgG positive, whereas 4 (3%) of 149
      were ELISA IgM positive. These findings demonstrate the acceptable performance of
      the Euroimmun ELISAs for Brucella antibodies.

PMID- 19748419
TI  - Cutoff values for bacteria and leukocytes for urine flow cytometer Sysmex UF
      1000i in urinary tract infections.
AB  - Because urinary tract infections (UTIs) are a quite common disease, the gold
      standard for diagnosing UTIs is still bacterial culture, although a large
      percentage of samples are negative: unnecessary cultures can be reduced by means
      of an effective screening test. The analytic performance of a new urine
      cytometer, the UF-1000i, has been tested on 1463 urine samples submitted to our
      laboratory for culture. Bacteria and leukocyte counts have been compared by means
      of the UF-1000i with colony-forming unit (CFU) quantification on citrate lactose
      electrolytes deficient agar to assess the best cutoff values. By using
      quantitative cultures and considering as positive a sample with 10 x 10(5)
      CFU/mL, 546 positive samples (37%) were observed. If compared with 10 x 10(5)
      CFU/mL, the cutoff values obtained were 125 bacteria/microL and 40 leukocytes/
      microL, respectively. Analytic parameters such as sensitivity, specificity,
      positive predictive value, negative predictive value, and correctly classified
      incidence were satisfactory. Based on the results obtained in this study, when
      using the UF-1000i analyzer for a screening test for UTI, a cutoff value of 40
      white blood cells/microL should be adopted. The cutoff value for bacteria should
      be 125/microL for those clinical conditions in which 10 x 10(5) CFU/mL indicates
      a positivity.

PMID- 19748420
TI  - Evaluation of the Copan ESwab transport system for the detection of methicillin
      resistant Staphylococcus aureus: a laboratory and clinical study.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as an important
      pathogen. Successful detection starts with the selection of an appropriate
      specimen collection device. The Copan ESwab, a new swab, was compared with a
      commonly used Copan Venturi swab for the recovery of MRSA. In vitro assessment
      was performed according to the Clinical and Laboratory Standards Institute (CLSI)
      M40-A protocol. For the clinical evaluation, 24 patients with known MRSA carriage
      were included. The ESwab fulfilled the CLSI acceptance criteria for MRSA
      viability. In the clinical study, both swabs performed equally in qualitative
      terms of positive and negative. However, the in vitro and in vivo evaluation
      revealed at least 3.6-fold higher recovery of viable MRSA with the ESwab as
      compared with the Venturi swab. In conclusion, the ESwab may contribute to
      improve the quality of a MRSA screening protocol.

PMID- 19748421
TI  - The Staphylococcus aureus lineage-specific markers collagen adhesin and toxic
      shock syndrome toxin 1 distinguish multilocus sequence typing clonal complexes
      within spa clonal complexes.
AB  - Spa typing/based upon repeat pattern (BURP) sometimes cannot differentiate
      multilocus sequence typing (MLST) clonal complexes (CCs) within spa-CCs. It has
      been observed previously that virulence factors, such as collagen adhesin (CNA)
      and toxic shock syndrome toxin 1 (TSST-1), are associated with certain
      Staphylococcus aureus lineages. Analysis of methicillin-sensitive and methicillin
      resistant S. aureus by spa typing/BURP and detection of CNA and TSST-1 observed
      an association between CNA and MLST CC1, 12, 22, 30, 45, 51, and 239 and between
      TSST-1 and MLST CC30. In spa-CC 012, associated with MLST CC7, CC15, and CC30,
      MLST CC30 could be distinguished from MLST CC7 and CC15 with CNA and TSST-1 as
      lineage-specific markers. Lineage-specific markers can overcome clustering of
      nonrelated MLST CCs into 1 spa-CC.

PMID- 19748422
TI  - Exposure-response analyses of tigecycline tolerability in healthy subjects.
AB  - Tigecycline exposure (area under the concentration-time curve [AUC((0-infinity))]
      and maximum serum concentration [C(max)]) and first occurrence of nausea and
      vomiting were evaluated in 136 healthy subjects after 12.5- to 300-mg single
      doses. Nausea was more frequent in females (46%, 10/22) compared with males (31%,
      11/36) after 100-mg doses. Most nausea (vomiting) events occurred < or =4 h (<6
      h) after tigecycline. For doses < or =100 mg, the median duration of nausea and
      vomiting was approximately 5 h. Based on logistic regression, increased exposure
      (AUC((0-infinity)) >C(max)) to tigecycline results in an increased rate of nausea
      (P < or = .0001; = .0022) and vomiting (P < or = .0001; = .0006). At the median
      AUC((0-infinity)) (C(max)) for the 50-mg dose group, the probability of nausea
      and vomiting was 0.26 (0.29) and 0.07 (0.11), respectively. Model-predicted rates
      of nausea and vomiting were comparable with those observed for the tetracycline
      class of antibiotics, with tolerable rates predicted after 50-mg doses of
      tigecycline.

PMID- 19748423
TI  - Comparison of the pharmacokinetics and pharmacodynamic profile of carumonam in
      cystic fibrosis patients and healthy volunteers.
AB  - Our objectives were to compare the pharmacokinetics (PK) of carumonam, a
      monobactam, between cystic fibrosis (CF) patients and healthy volunteers and
      assess its pharmacodynamic profile. We studied 10 adult CF patients and 18
      healthy volunteers of similar body size (dose: 2.166 g of carumonam as 15-min
      intravenous infusion). High performance liquid chromatography with ultraviolet
      detection (HPLC-UV) was used for drug analysis and NONMEM (ICON, Ellicot City,
      MD) for population PK and Monte Carlo simulation with targets between > or =20%
      and 100% free time above MIC (fT > MIC). Unscaled renal clearance was 24% higher
      in CF patients. Lean body mass and creatinine clearance explained the difference
      in average clearance and volume of distribution between both subject groups. For
      a daily dose of 6 g per 70 kg of total body weight, 15-min infusions q8h achieved
      robust (>90%) probabilities of target attainment (PTAs) (target, 60% fT > MIC)
      for MICs < or =3 mg/L in CF patients and < or =6 mg/L in healthy volunteers. At
      the same dose, 4-h infusions q8h achieved robust PTAs up to markedly higher MICs
      < or =8 to 12 mg/L in CF patients and < or =16 mg/L in healthy volunteers.

PMID- 19748424
TI  - Development and evaluation of antigen capture ELISA for early clinical diagnosis
      of chikungunya.
AB  - The resurgence of chikungunya (CHIK) in the form of unprecedented explosive
      epidemic after a gap of 3 decades in India and Indian Ocean islands is a point of
      major public health concern. The laboratory diagnosis is essentially based on
      virus isolation, IgM ELISA, and reverse transcriptase polymerase chain reaction
      (RT-PCR). Although PCR-based methods are used for early and accurate diagnosis,
      the high cost of the assay and requirement of thermal cycler limit its
      application only to referral laboratories. The antibody-based IgM ELISA is found
      to be cost-effective, but it takes 5 to 6 days for the patient to develop
      antibody and, thus, has less implication for early clinical diagnosis and patient
      management. Therefore, a simple rapid, sensitive, and specific antigen detection
      system is reported for early and reliable clinical diagnosis as well as effective
      surveillance of CHIK. A double antibody sandwich system was designed for antigen
      capture ELISA, employing rabbit and mouse anti-CHIK IgG antibodies as capture and
      detector antibodies, respectively. An optimal assay condition with 0 background
      was established having no reactivity with healthy human serum and Cerebro spinal
      fluid (CSF) samples. The comparative evaluation with SYBR Green I-based real-time
      RT-PCR revealed an accordance of 96% with a sensitivity and specificity of 95%
      and 97%, respectively. The specificity of this assay was confirmed through cross
      reactivity studies with confirmed dengue and Japanese encephalitis (JE) patient
      serum and CSF samples. The antigen capture ELISA reported in this study was able
      to detect the presence of viral antigen as early as the second day of fever and,
      thus, can be very useful for early clinical diagnosis of CHIK with acute phase
      patient serum and CSF samples. This can also be used for rapid screening of large
      numbers of clinical samples in endemic areas during epidemics.

PMID- 19748425
TI  - A duplex real-time reverse transcriptase polymerase chain reaction assay for the
      detection of California serogroup and Cache Valley viruses.
AB  - A duplex TaqMan real-time reverse transcriptase polymerase chain reaction (PCR)
      assay was developed for the detection of California (CAL) serogroup viruses and
      Cache Valley virus (CVV), for use in human surveillance. The targets selected for
      the assay were the sequences encoding the nucleocapsid protein of CAL and the G1
      glycoprotein of CVV. Conserved regions were selected by aligning genetic
      sequences from various strains available in the GenBank database. Primers and
      probes were selected in conserved regions. The assay sensitivity was 75 gene
      copies (gc)/reaction for CAL serogroup viruses and 30 gc/reaction for CVV. The
      performance of the assay was linear over at least 6 log(10) gc. The assay was
      specific, given that it did not cross-react with a variety of pathogens. It did,
      however, detect 11 viruses within the CAL serogroup and 12 CVV isolates. The use
      of an internal control ensured that possible inefficiency in nucleic acid
      extraction or PCR inhibition would be detected.

PMID- 19748426
TI  - Antimicrobial susceptibility of Gram-positive bacteria isolated from US medical
      centers: results of the Daptomycin Surveillance Program (2007-2008).
AB  - Gram-positive bacterial strains (12 443) consecutively collected during 2007 to
      2008 in hospitals located in the United States were tested by reference broth
      microdilution methods against daptomycin and comparison agents. Methicillin
      (oxacillin) resistance rates were 55.9% and 74.0% for Staphylococcus aureus and
      coagulase-negative staphylococci, respectively, and the vancomycin resistance
      rate among Enterococcus faecalis and Enterococcus faecium were 5.4% and 75.4%,
      respectively. Daptomycin was very active against all Gram-positive species with
      MIC(90) values of 0.5, 0.25, 0.5, and 2 microg/mL for staphylococci, beta
      hemolytic streptococci, viridans group streptococci, and enterococci,
      respectively. Overall, 99.9% of S. aureus, 100.0% of E. faecalis, and 99.5% of E.
      faecium were susceptible to daptomycin. In addition, daptomycin MIC distributions
      for S. aureus and enterococci from 2007 to 2008 were very similar to those from
      2002 to 2003. In summary, high rates of methicillin-resistant staphylococci and
      vancomycin-resistant enterococci were observed in US hospitals, but daptomycin
      remains active against these clinically important Gram-positive organisms with no
      evidence of potency loss since its approval for clinical use in late 2003.

PMID- 19748427
TI  - Combination of IMP-4 metallo-beta-lactamase production and porin deficiency
      causes carbapenem resistance in a Klebsiella oxytoca clinical isolate.
AB  - This study shows for the first time the mechanism of carbapenem resistance of a
      Klebsiella oxytoca clinical isolate ZC101 recovered from a Zhejiang University
      Hospital in Hangzhou, China. MIC values of imipenem, meropenem, and ertapenem for
      K. oxytoca ZC101 were 16, 16, and 128 microg/mL, respectively. Conjugation
      experiments demonstrated the transferability of a resistance determinant from K.
      oxytoca ZC101 to Escherichia coli EC600. Results from isoelectric focusing,
      polymerase chain reactions, and DNA sequencing confirmed that K. oxytoca ZC101
      produced IMP-4 metallo-beta-lactamase (MBL) and CTX-M-14 extended-spectrum beta
      lactamase, whereas E. coli transconjugant only produced the IMP-4. Amplification
      of integron revealed that bla(IMP-4) gene is located within a class I integron
      that was carried in a plasmid approximately 55 kb in size. Sodium dodecyl sulfate
      polyacrylamide gel electrophoresis profiling of outer membrane proteins of K.
      oxytoca ZC101 indicated lack of expression of the OmpK36 porin. DNA sequence
      analysis of ompK36 gene of K. oxytoca ZC101 showed the gene was disrupted by an
      insertion sequence IS5. In all, the results show that plasmid-mediated IMP-4 MBL
      production combined with the loss of OmpK36 porin caused the resistance in K.
      oxytoca ZC101 to carbapenems.

PMID- 19748428
TI  - Cost analysis and antimicrobial susceptibility testing comparing the E test and
      the agar dilution method in Campylobacter jejuni and Campylobacter coli.
AB  - Although numerous reports have compared the antimicrobial susceptibility of
      Campylobacter spp., controversy still exists about the use of the E test as an
      alternative to the agar dilution method suggested by the Clinical and Laboratory
      Standards Institute. MICs of 8 antimicrobials were determined using the E test
      and agar dilution methods for 103 Campylobacter jejuni and Campylobacter coli
      isolates from fresh chicken randomly purchased from stores in 3 southern Ontario
      counties. Overall, 72.6% of E test MIC values were within 1 log(2) dilution and
      95.7% within 2 log(2) dilutions of the corresponding agar dilution MICs. For
      individual antimicrobials, agreement within 1 log(2) dilution and 2 log(2)
      dilutions was as follows: ampicillin (n = 103), 90.3% and 98.1%, respectively;
      chloramphenicol (n = 104), 85.6% and 99%; ciprofloxacin (n = 99), 51.5% and
      97.0%; clindamycin (n = 99), 26.3% and 78.8%; erythromycin (n = 99), 52.5% and
      96.0%; gentamicin (n = 99), 100% and 100%; nalidixic acid (n = 98), 91.8% and
      99.0%; and tetracycline (n = 86), 82.6% and 97.7%. Relative to agar dilution, the
      E test underestimated the MIC value by a mean of 0.74 (ampicillin), 0.82
      (chloramphenicol), 1.44 (ciprofloxacin), 1.94 (clindamycin), 1.40 (erythromycin),
      0.21 (gentamicin), 0.94 (nalidixic acid), and 0.20 (tetracycline) log(2)
      dilutions and by a median of 1 log(2) dilution for all antimicrobials except
      clindamycin (2), gentamicin (0), and tetracycline (0). Cost analysis, including
      materials and labor, showed a 39.0% higher cost per analyte for the agar dilution
      method as compared with the E test. The most relevant advantage of the E test
      over the agar dilution method is the turnaround time because testing 99 strains
      by the agar dilution method takes 3.6 times longer compared with the E test using
      the same number of strains. The E test is an acceptable alternative for
      antimicrobial susceptibility testing in Campylobacter because it corresponds well
      with the agar dilution method although being considerably less expensive, is less
      labor intensive, and is more rapid. However, the relationship between E test and
      agar dilution MICs must be considered when interpreting E test results.

PMID- 19748429
TI  - Clinical failure of vancomycin in a dialysis patient with methicillin-susceptible
      vancomycin-heteroresistant S. aureus.
AB  - We report a case of recurrent Staphylococcus aureus bacteremia in a patient who
      failed vancomycin due to a vancomycin-heteroresistant strain lacking methicillin
      resistance. Although initial isolates were susceptible, isolates obtained after
      vancomycin chemotherapy were vancomycin heteroresistant. This case thus
      illustrates the clinical emergence of vancomycin heteroresistance.

PMID- 19748430
TI  - Infective endocarditis and osteomyelitis caused by Cellulomonas: a case report
      and review of the literature.
AB  - Cellulomonas spp. are often believed to be of low virulence and have never been
      reported as a pathogen causing human disease before. We report the first case of
      endocarditis caused by Cellulomonas and complicated with osteomyelitis of the
      lumbar spine in a 78-year-old woman. General weakness and aggravated lower back
      pain followed by sudden-onset of fever and chills were the major presentation.
      The diagnosis of infective endocarditis in this case was definitely using the
      Duke criteria. The magnetic resonance imaging of the lumbar spine revealed
      infective spondylodisciitis at an early stage. After a full course of antibiotics
      treatment, the patient's fever subsided but her lower back pain persisted. A slow
      clinical response to appropriate antimicrobial agents was characteristic of Gram
      positive bacillary endocarditis.

PMID- 19748431
TI  - Selection of colistin-resistant Acinetobacter baumannii isolates in
      postneurosurgical meningitis in an intensive care unit with high presence of
      heteroresistance to colistin.
AB  - Colistin heteroresistance in Acinetobacter baumannii (Ab) has been reported, but
      the clinical impact and the antimicrobial treatment have not been established
      yet. We observed the selection intratreatment with colistin of Ab colistin
      resistant strains from a colistin-heteroresistant isolate in one patient with
      postneurosurgical meningitis. The presence and the genetic relationship of
      heteroresistant Ab isolates from intensive care units (ICUs) obtained in the same
      period of the case report were analyzed. Twenty-eight isolates from patients
      admitted to the ICUs of an Argentinian university hospital during June to
      December 2004 were evaluated. Genomoespecie was determined by amplified ribosomal
      DNA restriction analysis, and genetic similarity among the strains was determined
      by pulsed-field electrophoresis. Colistin heteroresistance was observed in 46, 4%
      of these isolates. The majority belonged to clones previously identified as I and
      III.

PMID- 19748432
TI  - Comparison between pp65 antigenemia assay and quantitative real-time polymerase
      chain reaction for detection of active cytomegalovirus infection in routine
      diagnostics.
AB  - Real-time polymerase chain reaction (PCR) and pp65 antigenemia assay for the
      detection of active cytomegalovirus infection in immunocompromised patients
      experiencing neutropenia after bone marrow or kidney transplantation have been
      compared with a special focus on evaluability and embedment in daily routine
      diagnostics. Investigating 334 specimens from 97 patients, real-time PCR was
      shown to be the superior assay with regard to the parameters focused on.

PMID- 19748433
TI  - In vitro activity of daptomycin against Staphylococcus aureus and vancomycin
      resistant Enterococcus faecium isolates associated with skin and soft tissue
      infections: first results from India.
AB  - The in vitro activity of daptomycin and selected comparator agents against
      Staphylococcus aureus and vancomycin-resistant Enterococcus faecium (VREF)
      isolates recovered from hospitalized patients with skin and soft tissue
      infection's was evaluated by Clinical and Laboratory Standards Institute broth
      microdilution method. Daptomycin was the most active agent against both S. aureus
      (MIC(90), 1 microg/mL; 100% susceptible) and VREF (MIC(90), 4 microg/mL; 100%
      susceptible), making it an excellent therapeutic option.

PMID- 19748434
TI  - Change in the molecular epidemiology of methicillin-resistant Staphylococcus
      aureus bloodstream infections in Taiwan.
AB  - A multiresistant community-associated methicillin-resistant Staphylococcus aureus
      clone (sequence type 59) established itself as a significant cause of nosocomial
      bloodstream infections soon after emergence in the communities. Multiresistance
      might be one of the characteristics that could have contributed to its quick
      adaptation to hospital environments.

PMID- 19748435
TI  - Predominance of CTX-M-type extended-spectrum beta-lactamase genes among
      enterobacterial isolates from outpatients in Brazil.
AB  - Two hundred fifty-seven nalidixic acid-resistant enterobacterial isolates were
      collected in a Brazilian community from January 2000 to May 2005 to determine the
      prevalence of plasmid-encoded extended-spectrum beta-lactamases. The bla(CTX-M)
      genetic environment was determined by polymerase chain reaction and sequencing.
      Eleven isolates (4.2%) harbored a bla(CTX-M-2) gene, 3 isolates bla(CTX-M-9), 2
      isolates bla(CTX-M-8), and 6 isolates bla(SHV-5). Two novel bla(CTX-M-2)
      variants, namely, bla(CTX-M-74) and bla(CTX-M-75), were identified.

PMID- 19748436
TI  - Impact of human serum albumin on oritavancin in vitro activity against
      Staphylococcus aureus.
AB  - Human serum albumin (HSA) did not affect oritavancin MICs against non-vancomycin
      intermediate Staphylococcus aureus (non-VISA) strains. In time-kill assays,
      oritavancin bactericidal activity in the presence of HSA was significantly more
      rapid than comparators against non-VISA strains. HSA increased oritavancin MICs
      by 4-fold for VISA strains, reflective of reduced oritavancin activity in time
      kill assays with HSA.

PMID- 19748437
TI  - Specific IgG avidity in active and inactive human neurocysticercosis.
AB  - IgG avidity determination in serum samples was investigated to distinguish active
      and inactive human neurocysticercosis (NC). High avidity index (>70%) was found
      in 23.5% of cases in active group and 67.9% in inactive group (P = 0.0058). We
      reported for the first time that IgG avidity assay may distinguish active from
      inactive NC.

PMID- 19748438
TI  - Characterization of class 1 integrons and gene cassettes in clinical isolates of
      Klebsiella pneumoniae from Taiwan.
AB  - We surveyed the prevalence and contents of class 1 integrons in clinical
      Klebsiella pneumoniae isolates collected from Kaohsiung, Taiwan, during 2 periods
      (1993 and 2004). Class 1 integrons were present in 78 isolates (34.2%) from 1993
      (n = 228) and 129 (32.9%) from 2004 (n = 392) and contained varied gene cassette
      number, type, and array. We found 2 atypical sul3-associated class 1 integrons
      and identified 26 different gene cassettes, including an aac(6')-Ib-cr cassette
      here firstly described in K. pneumoniae from Taiwan. The continuing evolution of
      class 1 integrons is threatening to undermine the effectiveness of antimicrobial
      therapy for K. pneumoniae.

PMID- 19748439
TI  - Toll-like receptors (TLRs) and Nod-like receptors (NLRs) in inflammatory
      disorders.
AB  - Toll-like receptors (TLRs) and Nod-like receptors (NLRs) are two major forms of
      innate immune sensors, which provide immediate responses against pathogenic
      invasion or tissue injury. Activation of these sensors induces the recruitment of
      innate immune cells such as macrophages and neutrophils, initiates tissue repair
      processes, and results in adaptive immune activation. Abnormalities in any of
      these innate sensor-mediated processes may cause excessive inflammation due to
      either hyper responsive innate immune signaling or sustained compensatory
      adaptive immune activation. Recent gene association studies appear to reveal
      strong associations of NLR gene mutations and development of several idiopathic
      inflammatory disorders. In contrast, TLR polymorphisms are less often associated
      with inflammatory disorders. Nevertheless, TLRs are up-regulated in the affected
      tissue of most inflammatory disorders, suggesting TLR signaling is involved in
      the pathogenesis of chronic and/or idiopathic inflammatory disorders. NLR
      signaling results in the formation of a molecular scaffold complex (termed an
      inflammasome) and orchestrates with TLRs to induce IL-1beta and IL-18, both of
      which are important mediators in the majority of inflammatory disorders.
      Therefore, understanding the roles of TLRs and NLRs in the pathogenesis of
      chronic and idiopathic inflammatory disorders may provide novel targets for the
      prevention and/or treatment of many common and uncommon diseases involving
      inflammation.

PMID- 19748441
TI  - Car versus bicycle.

PMID- 19748444
TI  - What would mom say?

PMID- 19748446
TI  - HELLP syndrome A-Z: facing an obstetric emergency.

PMID- 19748447
TI  - For emergency medical service helicopter pilots, all wind is local.

PMID- 19748448
TI  - CALSTAR--committed to another 25 years of safe and secure patient transports.

PMID- 19748449
TI  - Air medical transport conference 2009.

PMID- 19748450
TI  - Transport nurse safety practices, perceptions, and experiences: the air and
      surface transport nurses association survey.

PMID- 19748451
TI  - Towards predicting bluetongue.

PMID- 19748452
TI  - [Esca and Black Dead Arm: two major actors of grapevine trunk diseases].
AB  - Grapevine trunk diseases are very harmful to wine-growing heritage durability
      because the fungi responsible, by attacking perennial organs, cause at a more or
      less long-term the death of the vine stock. Esca and BDA are the two main
      pathogens inducing such decaying diseases. The infection can be diagnosed by the
      presence in the wood forming tissues of sectorial and/or central necrosis, which
      revealed itself by brown stripes or canker, and at the foliar level by
      discoloration and withering. This review presents an overview of both Esca and
      BDA, their symptomatology, the characteristics of the associated fungi and host
      pathogen interactions. To conclude, a progress report on the control of both
      diseases is discussed.

PMID- 19748453
TI  - Comparative effect of potassium on K and Na uptake and transport in two
      accessions of Arabidopsis thaliana during salinity stress.
AB  - Potassium-sodium interaction was compared in two natural accessions of
      Arabidopsis thaliana, Columbia-0 and NOK2. Seedlings were grown in the presence
      of 0 or 50 mM NaCl and 0.1; 0.625 or 2.5 mM K(+). At the lowest K(+)
      concentration, salt treatment inhibited both K(+) uptake and growth. Increasing
      the K(+) availability did not modified salt response in Columbia-0, but restored
      nearly normal net K(+) uptake in NaCl condition and alleviated NaCl growth
      reduction in NOK2. The effect of K(+) and NaCl on transcript level of several
      K(+) and Na(+) transporters in both shoots and roots was assessed using semi
      quantitative RT-PCR. The mRNA abundance of the NHX1 and SOS1 Na(+)/H(+)
      antiporters was significantly increased by 50 mM NaCl in the two accessions.
      NHX1, which is responsible for Na(+) sequestration into vacuoles, was more up
      regulated in NOK2 leaves than in Columbia-0's in NaCl stress condition. AKT1,
      which is the major channel involved in K(+) absorption, was down-regulated in
      salt stress condition, but was not responding to K(+) treatments. Only in NOK2,
      SKOR and AKT2, which respectively control xylem and phloem K(+) transport, were
      markedly up-regulated by 2.5 mM K(+) in both roots and shoots, independently of
      NaCl. Phenotypic and gene expression analyses suggest that the relative salt
      tolerance of NOK2 is mainly due to a high ability to sequester Na(+) in the
      vacuole and to take up and transport K(+). Up-regulation of SKOR and AKT2 by
      K(+), and of NHX1 by NaCl could participate in determining this phenotype.

PMID- 19748454
TI  - [Life history traits of the snail Helix aperta Born from Tunisia raised in a
      laboratory environment: influence of photoperiod].
AB  - The present work revealed that growth and reproduction of Helix aperta (syn.
      Cantareus apertus), sampled at the end of summer in the region of Bazina
      (Tunisia), are stimulated by short-day photoperiod (SD 8hL-16hD) and inhibited by
      long-day photoperiod (LD 18hL-6hD). Indeed, under SD at 20 degrees C, 80%
      humidity and ad libitum Helixal snail food, 2 generations (F1, F2) were obtained
      in 10 months with no refractory period. The effects of photoperiod on growth were
      found to be reversible and appeared after a time lag of 4 and 8 weeks for
      stimulation by SD and the inhibition by LD respectively.

PMID- 19748455
TI  - Dormancy and germination responses of halophyte seeds to the application of
      ethylene.
AB  - Ethylene is invariably produced during seed germination but its role in
      regulating seed dormancy and germination is poorly understood. Seeds of 22
      halophytic species having different life forms - salt secreting dicots, salt
      secreting monocots, stem succulents and leaf succulents were germinated in Petri
      dishes kept in a growth chamber set at 20/30 degrees C (night/day) temperature
      and a 12 hr light period. Sodium chloride and ethephon were added to the medium
      from the beginning of the experiment. Seed germination was recorded every other
      day for twenty days. Application of ethylene did not have any significant effect
      on releasing seeds from innate dormancy. However, it appeared to have a role in
      alleviation of salinity effects which varied from negative in certain species to
      almost complete alleviation of high salinity effects in others. Our data
      indicates that ethylene appears to have little role in breaking innate seed
      dormancy however, in most halophyte seeds studied, application of ethylene
      alleviate the salinity effect to various degrees. Halophyte seeds which could
      germinate under saline conditions approaching twice the salinity of seawater may
      offer clues to understand management of seed germination under highly saline
      conditions.

PMID- 19748456
TI  - Phenolic composition and antioxidant activities of two Phlomis species: A
      correlation study.
AB  - Two traditional Chinese medicines (Phlomis umbrosa Turcz. and Phlomis megalantha
      Diels), as well as five pure phenolic compounds (protocatechic, chlorogenic,
      benzoic, rosmarinic acid, and rutin) have been studied for antioxidant activities
      in acetone and methanol extracts from leaves. An HPLC method was developed to
      quantify the amounts of 14 phenolic compounds in the leaf extracts. The
      antioxidant capacities of the studied species are high. Almost all samples were
      capable of directly scavenging DPPH and superoxide free radicals, inhibiting
      linoleic acid oxidation, acting as reducing agents, and reducing plasmid DNA
      damage induced by hydroxyl radicals. Among different extracts, the acetone
      extract of P. megalantha exhibited the highest antioxidant activity. The major
      phenolic compounds identified were protocatechic, chlorogenic, caffeic,
      rosmarinic acid, and (-)-epicatechin. Antioxidant activities of pure compounds
      and correlation analysis indicated that protocatechic and rosmarinic acids were
      the major contributors to the observed antioxidant activities of the investigated
      Phlomis extracts.

PMID- 19748457
TI  - Exploring the antioxidant potential of lignin isolated from black liquor of oil
      palm waste.
AB  - This study was conducted to evaluate the potential antioxidant activity of lignin
      obtained from black liquor, a hazardous waste product generated during the
      extraction of palm oil. Antioxidant potential of the extracted lignin was
      evaluated by dissolving the extracted samples in 2 different solvent systems,
      namely, 2-methoxy ethanol and DMSO. Results revealed high percent inhibition of
      the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical in the lignin sample dissolved
      in 2-methoxy ethanol over DMSO (concentration range of 1-100 microg/ml). Lignin
      extracted in 2-methoxy ethanol exhibited higher inhibition percentage (at 50
      microg/ml, 84.2%), whereas a concentration of 100 microg/ml was found to be
      effective in the case of the DMSO solvent (69.8%). Fourier transform infrared
      (FTIR) spectrometry revealed that the functional groups from the extracted lignin
      and commercial lignin were highly similar, indicating the purity of the lignin
      extracted from black liquor. These results provide a strong basis for further
      applications of lignin in the food industry and also illustrate an eco-friendly
      approach to utilize oil palm black liquor.

PMID- 19748458
TI  - SuperTRI: A new approach based on branch support analyses of multiple independent
      data sets for assessing reliability of phylogenetic inferences.
AB  - Supermatrix and supertree are two methods for constructing a phylogenetic tree by
      using multiple data sets. However, these methods are not a panacea, as
      conflicting signals between data sets can lead to misinterpret the evolutionary
      history of taxa. In particular, the supermatrix approach is expected to be
      misleading if the species-tree signal is not dominant after the combination of
      the data sets. Moreover, most current supertree methods suffer from two
      limitations: (i) they ignore or misinterpret secondary (non-dominant)
      phylogenetic signals of the different data sets; and (ii) the logical basis of
      node robustness measures is unclear. To overcome these limitations, we propose a
      new approach, called SuperTRI, which is based on the branch support analyses of
      the independent data sets, and where the reliability of the nodes is assessed
      using three measures: the supertree Bootstrap percentage and two other values
      calculated from the separate analyses: the mean branch support (mean Bootstrap
      percentage or mean posterior probability) and the reproducibility index. The
      SuperTRI approach is tested on a data matrix including seven genes for 82 taxa of
      the family Bovidae (Mammalia, Ruminantia), and the results are compared to those
      found with the supermatrix approach. The phylogenetic analyses of the supermatrix
      and independent data sets were done using four methods of tree reconstruction:
      Bayesian inference, maximum likelihood, and unweighted and weighted maximum
      parsimony. The results indicate, firstly, that the SuperTRI approach shows less
      sensitivity to the four phylogenetic methods, secondly, that it is more accurate
      to interpret the relationships among taxa, and thirdly, that interesting
      conclusions on introgression and radiation can be drawn from the comparisons
      between SuperTRI and supermatrix analyses.

PMID- 19748459
TI  - Spatio-temporal variations of functional groups in a Populus nigra L.
      entomocenosis in the Mitidja plain (Algeria).
AB  - This study presents the first data describing the communities of insects and
      arachnida colonizing 4 aerial compartments of Populus nigra. In terms of temporal
      variation and total abundance, the analyses show that the communities are
      structurally and functionally different. It also appears that the taxonomic
      richness of the communities, and partly their temporal distribution, change
      according to the gradient of the energy and defense resources under the effect of
      seasonal variations. The highest species richness recorded on the leaves
      compartment is due to the amplitude of histo-physiological modifications observed
      throughout the growing season.

PMID- 19748460
TI  - Making sense of antisense in antibiotic drug discovery.
AB  - In an era of increasing antibiotic resistance, growing clinical need for new
      drugs, and few lead molecules, new research is helping to identify new targets
      and the mechanism of action of lead molecules.

PMID- 19748461
TI  - Shifting the paradigm: host gene signatures for diagnosis of infectious diseases.
AB  - Instead of focusing on the pathogen, in a paradigm shift, Zaas et al. (2009)
      identified host gene profiles as a strategy for diagnosis of respiratory
      infections. Application of host gene profiles offers tremendous possibilities for
      identification of diagnostic signatures, markers of disease severity, and
      eventually, prognostic indicators in the clinical setting.

PMID- 19748462
TI  - A vitamin for autophagy.
AB  - Recent discoveries have revealed the importance of the vitamin D-dependent
      generation of antimicrobial peptides in human host defense against Mycobacterium
      tuberculosis. Now, Yuk et al. (2009) show how vitamin D induces autophagy and
      mediates colocalization of Mycobacterium tuberculosis and antimicrobial peptides
      within an autophagolysosome, leading to killing of the bacterium.

PMID- 19748463
TI  - Host tolerance versus resistance and microbial virulence in the host-pathogen
      equation.
AB  - To deal with an infection, the organism resorts to nonmutually exclusive
      strategies: resistance, that is, neutralization or destruction of the pathogen;
      or tolerance, the ability to withstand damages inflicted by the pathogen or by
      host defense. In this issue of Cell Host & Microbe, Shinzawa et al. (2009)
      identify p38-mediated phagocytic encapsulation as a potential tolerance
      mechanism.

PMID- 19748464
TI  - Massive secretion by T cells is caused by HIV Nef in infected cells and by Nef
      transfer to bystander cells.
AB  - The HIV Nef protein mediates endocytosis of surface receptors that correlates
      with disease progression, but the link between this Nef function and HIV
      pathogenesis is not clear. Here, we report that Nef-mediated activation of
      membrane trafficking is bidirectional, connecting endocytosis with exocytosis as
      occurs in activated T cells. Nef expression induced an extensive secretory
      activity in infected and, surprisingly, also in noninfected T cells, leading to
      the massive release of microvesicle clusters, a phenotype observed in vitro and
      in 36%-87% of primary CD4 T cells from HIV-infected individuals. Consistent with
      exocytosis in noninfected cells, Nef is transferred to bystander cells upon cell
      to-cell contact and subsequently induces secretion in an Erk1/2-dependent manner.
      Thus, HIV Nef alters membrane dynamics, mimicking those of activated T cells and
      causing a transfer of infected cell signaling (TOS) to bystander cells. This
      mechanism may help explain the detrimental effect on bystander cells seen in HIV
      infection.

PMID- 19748465
TI  - Vitamin D3 induces autophagy in human monocytes/macrophages via cathelicidin.
AB  - Autophagy and vitamin D3-mediated innate immunity have been shown to confer
      protection against infection with intracellular Mycobacterium tuberculosis. Here,
      we show that these two antimycobacterial defenses are physiologically linked via
      a regulatory function of human cathelicidin (hCAP-18/LL-37), a member of the
      cathelicidin family of antimicrobial proteins. We show that 1,25-dihydroxyvitamin
      D3 (1,25D3), the active form of vitamin D, induced autophagy in human monocytes
      via cathelicidin, which activated transcription of the autophagy-related genes
      Beclin-1 and Atg5. 1,25D3 also induced the colocalization of mycobacterial
      phagosomes with autophagosomes in human macrophages in a cathelicidin-dependent
      manner. Furthermore, the antimycobacterial activity in human macrophages mediated
      by physiological levels of 1,25D3 required autophagy and cathelicidin. These
      results indicate that human cathelicidin, a protein that has direct antimicrobial
      activity, also serves as a mediator of vitamin D3-induced autophagy.

PMID- 19748466
TI  - p38 MAPK-dependent phagocytic encapsulation confers infection tolerance in
      Drosophila.
AB  - Hosts employ a combination of two distinct yet compatible strategies to defend
      themselves against parasites: resistance, the ability to limit parasite burden,
      and tolerance, the ability to limit damage caused by a given parasite burden.
      Animals typically exhibit considerable genetic variation in resistance to a
      variety of pathogens; however, little is known about whether animals can evolve
      tolerance. Using a bacterial infection model in Drosophila, we uncovered a p38
      MAP kinase-mediated mechanism of tolerance to intracellular bacterial infection
      as measured by the extent to which the host's survival rate increased or was
      maintained despite increasing bacterial burden. This increased survival was
      conferred primarily by a tolerance strategy whereby p38-dependent phagocytic
      encapsulation of bacteria resulted in enlarged phagocytes that trap bacteria.
      These results suggest that phagocytic responses are not restricted to resistance
      mechanisms but can also be applied to tolerance strategies for intracellular
      encapsulation of pathogens during the invertebrate immune response.

PMID- 19748467
TI  - The amoebal MAP kinase response to Legionella pneumophila is regulated by DupA.
AB  - The amoeba Dictyostelium discoideum can support replication of Legionella
      pneumophila. Here we identify the dupA gene, encoding a putative tyrosine
      kinase/dual-specificity phosphatase, in a screen for D. discoideum mutants
      altered in allowing L. pneumophila intracellular replication. Inactivation of
      dupA resulted in depressed L. pneumophila growth and sustained
      hyperphosphorylation of the amoebal MAP kinase ERK1, consistent with loss of a
      phosphatase activity. Bacterial challenge of wild-type amoebae induced dupA
      expression and resulted in transiently increased ERK1 phosphorylation, suggesting
      that dupA and ERK1 are part of a response to bacteria. Indeed, over 500 of the
      genes misregulated in the dupA(-) mutant were regulated in response to L.
      pneumophila infection, including some thought to have immune-like functions. MAP
      kinase phosphatases are known to be highly upregulated in macrophages challenged
      with L. pneumophila. Thus, DupA may regulate a MAP kinase response to bacteria
      that is conserved from amoebae to mammals.

PMID- 19748468
TI  - Regulatory mimicry in Listeria monocytogenes actin-based motility.
AB  - The actin-based motility of the intracellular pathogen Listeria monocytogenes
      relies on ActA, a bacterial factor with a structural domain allowing it to mimic
      the actin nucleation-promoting activity of host cell proteins of the WASP/WAVE
      family. Here, we used an RNAi-based genetic approach in combination with computer
      assisted image analysis to investigate the role of host factors in L.
      monocytogenes cell-to-cell spread. We showed that the host cell serine/threonine
      kinase CK2 is required for efficient actin tail formation by L. monocytogenes.
      Furthermore, CK2-mediated phosphorylation of ActA regulated its affinity for the
      actin-nucleating ARP2/3 complex, as is the case for CK2-mediated phosphorylation
      of WASP and WAVE. Thus, ActA not only displays structural mimicry of WASP/WAVE
      family members, but also regulatory mimicry, having precisely co-opted the host
      machinery regulating these proteins. Comparisons based on ActA amino acid
      sequence suggest that unrelated pathogens that display actin-based motility may
      have evolved a similar strategy of regulatory mimicry.

PMID- 19748469
TI  - Identifying genetic determinants needed to establish a human gut symbiont in its
      habitat.
AB  - The human gut microbiota is a metabolic organ whose cellular composition is
      determined by a dynamic process of selection and competition. To identify
      microbial genes required for establishment of human symbionts in the gut, we
      developed an approach (insertion sequencing, or INSeq) based on a mutagenic
      transposon that allows capture of adjacent chromosomal DNA to define its genomic
      location. We used massively parallel sequencing to monitor the relative abundance
      of tens of thousands of transposon mutants of a saccharolytic human gut
      bacterium, Bacteroides thetaiotaomicron, as they established themselves in wild
      type and immunodeficient gnotobiotic mice, in the presence or absence of other
      human gut commensals. In vivo selection transforms this population, revealing
      functions necessary for survival in the gut: we show how this selection is
      influenced by community composition and competition for nutrients (vitamin
      B(12)). INSeq provides a broadly applicable platform to explore microbial
      adaptation to the gut and other ecosystems.

PMID- 19748470
TI  - A liquid chromatography-tandem mass spectrometry assay for Marfey's derivatives
      of L-Ala, D-Ala, and D-Ala-D-Ala: application to the in vivo confirmation of
      alanine racemase as the target of cycloserine in Escherichia coli.
AB  - Bacterial cell wall biosynthesis is the target of several antibacterial agents
      and is also of interest as a target for future antibacterial agent development.
      Given the now widespread availability of liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) instruments, the development of LC-MS/MS assays for cell
      wall biosynthesis intermediates would fill a needed gap in the analytical
      methodology available for antibacterial agent discovery and characterization. An
      LC-MS/MS assay for several early cell wall intermediates-L-Ala, D-Ala, and D-Ala
      D-Ala-has been developed. This method relies on derivatization of bacterial
      extracts with Marfey's reagent. Marfey's reagent adducts of L-Ala and D-Ala were
      cleanly separated chromatographically, allowing Marfey's adducts of D-Ala and L
      Ala to be separated prior to mass spectrometry (MS) detection and quantitation.
      The Marfey's adduct of D-Ala-D-Ala was also readily detectable using this same
      approach. This method shows good linearity (R(2)>0.99), with a lower limit of
      quantitation of 1 pmol. This assay was demonstrated for characterization of the
      in vivo effect of cycloserine on Escherichia coli. Cycloserine resulted in a
      dramatic lowering of both D-Ala and D-Ala-D-Ala levels. Ampicillin had little
      effect on levels of these three metabolites, consistent with the actions of
      ampicillin on the later stages of cell wall biosynthesis. These observations
      indicate that cycloserine inhibits alanine racemase production of D-Ala in E.
      coli and demonstrates the utility of this assay in directly assessing D-Ala
      branch targeted antibacterial agents.

PMID- 19748471
TI  - A microtiter plate-based beta-lactam binding assay for inhibitors of high
      molecular-mass penicillin-binding proteins.
AB  - High-molecular-mass penicillin-binding proteins (HMM PBPs) are essential for
      bacterial cell wall biosynthesis and are the lethal targets of beta-lactam
      antibiotics. When purified, HMM PBPs give undetectable or weak enzyme activity.
      This has impeded efforts to develop assays for HMM PBPs and to develop new
      inhibitors for HMM PBPs as HMM PBP targeted antibacterial agents. However, even
      when purified, HMM PBPs retain their ability to bind beta-lactams. Here we
      describe a fluorescently detected microtiter plate-based assay for inhibitor
      binding to HMM PBPs based on competition with biotin-ampicillin conjugate (BIO
      AMP) binding.

PMID- 19748472
TI  - Red-emitting luciferases for bioluminescence reporter and imaging applications.
AB  - North American firefly Photinus pyralis luciferase, which emits yellow-green
      light (557nm), has been adapted for a variety of applications, including gene
      reporter assays, whole-cell biosensor measurements, and in vivo imaging.
      Luciferase variants with red-shifted bioluminescence and high specific activity
      can be paired with green-emitting counterparts for use in dual-color reporter
      assays or can be used alone for in vivo imaging. Beginning with a previously
      reported red-emitting thermostable mutant and using mutagenesis techniques, we
      engineered two luciferases with redder emission maxima while maintaining
      satisfactory specific activities and thermostability. The novel enzymes were
      expressed in HEK293 cells, where they performed similarly to Promega's codon
      optimized click beetle red luciferase in model reporter assays. When the firefly
      luciferase variants were codon-optimized and retested using optimized substrate
      concentrations, they provided 50- to 100-fold greater integrated light
      intensities than the click beetle enzyme. These results suggest that the novel
      enzymes should provide superior performance in dual-color reporter and in vivo
      imaging applications, and they illustrate the importance of codon optimization
      for assays in mammalian cells.

PMID- 19748473
TI  - A fast and efficient method for quantitative measurement of S-adenosyl-L
      methionine-dependent methyltransferase activity with protein substrates.
AB  - Modification of protein residues by S-adenosyl-L-methionine (AdoMet)-dependent
      methyltransferases impacts an array of cellular processes. Here we describe a new
      approach to quantitatively measure the rate of methyl transfer that is compatible
      with using protein substrates. The method relies on the ability of reverse-phase
      resin packed at the end of a pipette tip to quickly separate unreacted AdoMet
      from radiolabeled protein products. Bound radiolabeled protein products are
      eluted directly into scintillation vials and counted. In addition to decreasing
      analysis time, the sensitivity of this protocol allows the determination of
      initial rate data. The utility of this protocol was shown by generating a
      Michaelis-Menten curve for the methylation of heterogeneous nuclear
      ribonucleoprotein K (hnRNP K) protein by human protein arginine methyltransferase
      1, variant 1 (hPRMT1v1), in just over 1h. An additional advantage of this assay
      is the more than 3000-fold reduction in radioactive waste over existing
      protocols.

PMID- 19748474
TI  - A sensitive fluorimetric assay for pyruvate.
AB  - A sensitive and specific fluorimetric assay for the determination of pyruvate is
      reported here. This assay is based on the oxidation of pyruvate in the presence
      of pyruvate oxidase. Hydrogen peroxide generated by pyruvate oxidase reacts with
      nonfluorescent Amplex Red at a 1:1 stoichiometry to form the fluorescent product,
      resorufin. The assay is optimized with respect to pH of reaction buffer, enzyme
      concentration, dye concentration, and the time course. The usefulness of the
      assay is demonstrated by the accurate measurement of intracellular and
      extracellular pyruvate concentrations. The limit of detection of the assay is 5
      nM.

PMID- 19748475
TI  - Development of a colorimetric assay for heparanase activity suitable for kinetic
      analysis and inhibitor screening.
AB  - The role that heparanase plays during metastasis and angiogenesis in tumors makes
      it an attractive target for cancer therapeutics. Despite this enzyme's
      significance, most of the assays developed to measure its activity are complex.
      Moreover, they usually rely on labeling variable preparations of the natural
      substrate heparan sulfate, making comparisons across studies precarious. To
      overcome these problems, we have developed a convenient assay based on the
      cleavage of the synthetic heparin oligosaccharide fondaparinux. The assay
      measures the appearance of the disaccharide product of heparanase-catalyzed
      fondaparinux cleavage colorimetrically using the tetrazolium salt WST-1. Because
      this assay has a homogeneous substrate with a single point of cleavage, the
      kinetics of the enzyme can be reliably characterized, giving a K(m) of 46 microM
      and a k(cat) of 3.5 s(-1) with fondaparinux as substrate. The inhibition of
      heparanase by the published inhibitor, PI-88, was also studied, and a K(i) of 7.9
      nM was determined. The simplicity and robustness of this method, should, not only
      greatly assist routine assay of heparanase activity but also could be adapted for
      high-throughput screening of compound libraries, with the data generated being
      directly comparable across studies.

PMID- 19748476
TI  - Applications of luciferin biosynthesis: Bioluminescence assays for l-cysteine and
      luciferase.
AB  - Based on the biosynthetic pathway of firefly bioluminescence substrate D
      luciferin, the concentration of L-cysteine can be quantified using a simple
      protocol and a conventional luminescence detector. The lower limit of
      quantification (signal/noise ratio [S/N]=10) was 0.26 microM. Using our method,
      the total amount of free/reduced and disulfide/oxidized L-cysteine could be
      measured successfully in human serum. In addition, biosynthetic precursors such
      as 2-cyano-6-hydroxybenzothiazole and L-luciferin could replace d-luciferin in
      the cell-based luciferase assay. Our results suggest that the bioluminescence
      reaction associated with the biosynthesis of bioluminescence substrates can
      provide a fast and cost-effective assay method.

PMID- 19748477
TI  - Enzymatic stereospecific preparation of fluorescent S-adenosyl-L-methionine
      analogs.
AB  - S-Adenosyl-L-methionine (SAM) is the preferred cofactor for biological methyl
      group transfers to various substrates such as nucleic acids, proteins, and
      lipids. Here we present stereospecific (>95% of the desired enantiomer) and high
      yield preparation of four fluorescent and biologically active SAM analogs and
      demonstrate their usefulness in binding studies. Using a fluorescence titration
      experiment, we obtained a K(d) of 0.38 microM for the S-2,6
      diaminopurinylmethionine-SAM-III riboswitch complex.

PMID- 19748478
TI  - A nonradioactive plate-based assay for stimulators of nonspecific DNA nicking by
      HIV-1 integrase and other nucleases.
AB  - Retroviral integrase enzymes have a nonspecific endonuclease activity that is
      stimulated by certain compounds, suggesting that integrase could be manipulated
      to damage viral DNA. To identify integrase stimulator (IS) compounds as potential
      antiviral agents, we have developed a nonradioactive assay that is suitable for
      high-throughput screening. The assay uses a 49-mer oligonucleotide that is 5'
      labeled with a fluorophore, 3'-tagged with a quencher, and designed to form a
      hairpin that mimics radioactive double-stranded substrates in gel-based nicking
      assays. Reactions in 384-well plates are analyzed on a real-time PCR machine
      after a single heat denaturation and subsequent cooling to a point between the
      melting temperatures of unnicked substrate and nicked products (no cycling is
      required). Under these conditions, unnicked DNA reforms the hairpin and quenches
      fluorescence, whereas completely nicked DNA yields a large signal. The assay was
      linear with time, stimulator concentration, and amount of integrase, and 20%
      concentrations of the solvent used for many chemical libraries did not interfere
      with the assay. The assay had an excellent Z' factor, and it reliably detected
      known IS compounds. This assay, which is adaptable to other nonspecific
      nucleases, will be useful for identifying additional IS compounds to develop the
      novel antiviral strategy of stimulating integrase to destroy retroviral DNA.

PMID- 19748479
TI  - Metal-enhanced PicoGreen fluorescence: application for double-stranded DNA
      quantification.
AB  - PicoGreen (PG) is a fluorescent probe for both double-stranded DNA (dsDNA)
      detection and quantification based on its ability to form a luminescent complex
      with dsDNA as compared with the free dye in solution. To expand the sensitivity
      of PG detection, we have studied the spectral properties of PG, both free and in
      complex with DNA in solution, when the fluorophore is in proximity to silver
      nanoparticles. We show that for a broad range of PG concentrations (20 pM-3.5
      microM), it does not form dimers/oligomers and it exists in a monomeric state. On
      binding to DNA in the absence of silver, PG fluorescence increases approximately
      1100-fold. Deposition of PG/DNA complex onto silver island films (SiFs) increases
      fluorescence approximately 7-fold due to the metal-enhanced fluorescence (MEF)
      effect, yielding fluorescence enhancement of 7700-fold as compared with the free
      dye on glass. In contrast to PG in complex with DNA, the free dye on SiFs
      demonstrates a decrease in brightness approximately 5-fold. Therefore, the total
      enhancement of PG on binding to DNA on silver reaches a value of approximately
      38,000 as compared with free PG on SiFs. Consequently, the metal-enhanced
      detection of PG fluorescence is likely to find important utility for amplified
      dsDNA quantification.

PMID- 19748480
TI  - Development and validation of a cytochrome c-coupled assay for pteridine
      reductase 1 and dihydrofolate reductase.
AB  - Activity of the pterin- and folate-salvaging enzymes pteridine reductase 1 (PTR1)
      and dihydrofolate reductase-thymidylate synthetase (DHFR-TS) is commonly measured
      as a decrease in absorbance at 340 nm, corresponding to oxidation of nicotinamide
      adenine dinucleotide phosphate (NADPH). Although this assay has been adequate to
      study the biology of these enzymes, it is not amenable to support any degree of
      routine inhibitor assessment because its restricted linearity is incompatible
      with enhanced throughput microtiter plate screening. In this article, we report
      the development and validation of a nonenzymatically coupled screening assay in
      which the product of the enzymatic reaction reduces cytochrome c, causing an
      increase in absorbance at 550 nm. We demonstrate this assay to be robust and
      accurate, and we describe its utility in supporting a structure-based design,
      small-molecule inhibitor campaign against Trypanosoma brucei PTR1 and DHFR-TS.

PMID- 19748481
TI  - Regulation of the human SLC25A20 expression by peroxisome proliferator-activated
      receptor alpha in human hepatoblastoma cells.
AB  - Solute carrier family 25, member 20 (SLC25A20) is a key molecule that transfers
      acylcarnitine esters in exchange for free carnitine across the mitochondrial
      membrane in the mitochondrial beta-oxidation. The peroxisome proliferator
      activated receptor alpha (PPARalpha) is a ligand-activated transcription factor
      that plays an important role in the regulation of beta-oxidation. We previously
      established tetracycline-regulated human cell line that can be induced to express
      PPARalpha and found that PPARalpha induces the SLC25A20 expression. In this
      study, we analyzed the promoter region of the human slc25a20 gene and showed that
      PPARalpha regulates the expression of human SLC25A20 via the peroxisome
      proliferator responsive element.

PMID- 19748482
TI  - DcR3 protects THP-1 macrophages from apoptosis by increasing integrin alpha4.
AB  - In order to analyze the function of DcR3 for the regulation of cell adhesion and
      apoptosis in macrophages, we investigated the expression of decoy receptor 3
      (DcR3) in THP-1 monocytes/macrophages. DcR3 was expressed in THP-1 and increased
      by phorbol 12-myristate 13-acetate (PMA). The formation of macrophage aggregates
      was observed when THP-1 cells were differentiated by PMA or stimulated with DcR3
      Fc. Undifferentiated THP-1 cells were also induced to form aggregates by DcR3-Fc.
      The expression of integrin alpha4 was significantly increased by DcR3-Fc. CHX
      induced apoptosis in THP-1 was inhibited by DcR3-Fc, of which inhibition against
      CHX-induced apoptosis and aggregate formation were ameliorated by anti-VLA4
      antibody. DcR3 may play a significant role in macrophages not only by a decoy
      receptor but also by increasing alpha4 integrin.

PMID- 19748483
TI  - CpcF-dependent regulation of pigmentation and development in Fremyella
      diplosiphon.
AB  - Cyanobacteria harvest light for photosynthesis using photosynthetic light
      harvesting complexes called phycobilisomes (PBSs). Lyases are enzymes responsible
      for covalent attachment of light-absorbing chromophores to the phycobiliproteins
      (PBPs) contained in PBSs. We isolated a pigmentation mutant in the filamentous
      cyanobacterium Fremyella diplosiphon and determined that it possesses an
      insertional mutation in cpcF, which encodes one component of a heterodimeric
      phycocyanin lyase. Here, we discuss the implications of the mutation in cpcF on
      light-dependent pigmentation and morphology responses characteristic of
      complementary chromatic adaptation in F. diplosiphon. Although cpcF encodes a
      phycocyanin lyase, significant decreases in the levels of all classes of PBPs are
      associated with CpcF deficiency in F. diplosiphon. Notably, CpcF deficiency has a
      limited effect on the shape of F. diplosiphon cells, but significantly impacts
      filament length. Possible mechanisms for the broad impact of CpcF deficiency on
      pigmentation and filament morphology are discussed.

PMID- 19748484
TI  - Germline-like predecessors of broadly neutralizing antibodies lack measurable
      binding to HIV-1 envelope glycoproteins: implications for evasion of immune
      responses and design of vaccine immunogens.
AB  - Several human monoclonal antibodies (hmAbs) including b12, 2G12, and 2F5 exhibit
      relatively potent and broad HIV-1-neutralizing activity. However, their
      elicitation in vivo by vaccine immunogens based on the HIV-1 envelope
      glycoprotein (Env) has not been successful. We have hypothesized that HIV-1 has
      evolved a strategy to reduce or eliminate the immunogenicity of the highly
      conserved epitopes of such antibodies by using "holes" (absence or very weak
      binding to these epitopes of germline antibodies that is not sufficient to
      initiate and/or maintain an efficient immune response) in the human germline B
      cell receptor (BCR) repertoire. To begin to test this hypothesis we have designed
      germline-like antibodies corresponding most closely to b12, 2G12, and 2F5 as well
      as to X5, m44, and m46 which are cross-reactive but with relatively modest
      neutralizing activity as natively occurring antibodies due to size and/or other
      effects. The germline-like X5, m44, and m46 bound with relatively high affinity
      to all tested Envs. In contrast, germline-like b12, 2G12, and 2F5 lacked
      measurable binding to Envs in an ELISA assay although the corresponding mature
      antibodies did. These results provide initial evidence that Env structures
      containing conserved vulnerable epitopes may not initiate humoral responses by
      binding to germline antibodies. Even if such responses are initiated by very weak
      binding undetectable in our assay it is likely that they will be outcompeted by
      responses to structures containing the epitopes of X5, m44, m46, and other
      antibodies that bind germline BCRs with much higher affinity/avidity. This
      hypothesis, if further supported by data, could contribute to our understanding
      of how HIV-1 evades immune responses and offer new concepts for design of
      effective vaccine immunogens.

PMID- 19748485
TI  - Induction of JAM-A during differentiation of human THP-1 dendritic cells.
AB  - Junctional adhesion molecule (JAM)-A is not only localized at tight junctions of
      endothelial and epithelial cells but is also expressed on circulating leukocytes
      and dendritic cells (DCs). In the present study, to investigate the regulation of
      JAM-A in DCs, mature DCs were differentiated from the human monocytic cell THP-1
      by treatment with IL-4, GM-CSF, TNF-alpha, and ionomycin, and some cells were
      pretreated with the PPAR-gamma agonists. In the THP-1 monocytes, mRNAs of tight
      junction molecules, occludin, tricellulin, JAM-A, ZO-1, ZO-2 and claudin-4, -7, 
      8, and -9 were detected by RT-PCR. In mature DCs that had elongated dendrites,
      mRNA and protein of JAM-A were significantly increased compared to the monocytes.
      PPAR-gamma agonists prevented the elongation of dentrites but not upregulation of
      JAM-A in mature DCs. These findings indicated that the induction of JAM-A
      occurred during differentiation of human THP-1 DCs and was independent of PPAR
      gamma and the p38 MAPK pathway.

PMID- 19748486
TI  - Direct effects of osteoprotegerin on human bone cell metabolism.
AB  - PURPOSE: Osteoprotegerin (OPG) affects bone metabolism by intercepting the RANK
      RANKL interaction which prevents osteoclastic differentiation and consequently
      reduces bone resorption. Different bone phenotypes of mice overexpressing OPG and
      of mice with knockdown of receptor activator of NF-kappaB (RANK) or RANK-ligand
      (RANKL) suggest that the mechanism of action of the OPG-RANKL-RANK system in
      regulating bone remodeling is not completely understood. Furthermore, OPG
      increases bone mass and density independently from reduced osteoclastogenesis
      which is consistent with the possibility that OPG may directly affect bone
      metabolism beyond its known role as decoy receptor for RANKL. METHODS: We treated
      primary human osteoblastic cells with OPG and inhibitory anti-RANKL antibodies
      and measured cellular ALP activity, in vitro mineralization, vitronectin receptor
      protein expression and ERK phosphorylation. We also analyzed the mRNA co
      expression of ALP and OPG ex vivo in bone biopsies from acute and old stable
      vertebral fractures. RESULTS: OPG directly increased ALP activity and in vitro
      mineralization of HOC, enhanced expression of the vitronectin receptor thereby
      increasing adherence of HOC to vitronectin and stimulated ERK phosphorylation.
      All OPG-mediated effects could be prevented by RANKL antibodies or RANKL-siRNA
      transfection and MAPK inhibitor PD98059 reduced the stimulatory effect of OPG on
      integrin alphav expression. In acutely fractured vertebrae OPG and ALP mRNA
      expression was significantly increased compared to stable vertebral fractures. In
      conclusion, OPG exerts direct osteoanabolic effects on HOC metabolism via RANKL
      in addition to its well described role as decoy receptor for RANKL.

PMID- 19748487
TI  - The plasmodium receptor for activated C kinase protein inhibits Ca(2+) signaling
      in mammalian cells.
AB  - Plasmodium falciparum, the most lethal malarial parasite, expresses an ortholog
      for the protein kinase C (PKC) activator RACK1. However, PKC has not been
      identified in this parasite, and the mammalian RACK1 can interact with the
      inositol 1,4,5-trisphosphate receptor (InsP3R). Therefore we investigated whether
      the Plasmodium ortholog PfRACK also can affect InsP3R-mediated Ca(2+) signaling
      in mammalian cells. GFP-tagged PfRACK and endogenous RACK1 were expressed in a
      similar distribution within cells. PfRACK inhibited agonist-induced Ca(2+)
      signals in cells expressing each isoform of the InsP3R, and this effect persisted
      when expression of endogenous RACK1 was reduced by siRNA. PfRACK also inhibited
      Ca(2+) signals induced by photorelease of caged InsP3. These findings provide
      evidence that PfRACK directly inhibits InsP3-mediated Ca(2+) signaling in
      mammalian cells. Interference with host cell signaling pathways to subvert the
      host intracellular milieu may be an important mechanism for parasite survival.

PMID- 19748488
TI  - Endothelin-1 induces the expression of C-reactive protein in rat vascular smooth
      muscle cells.
AB  - Numerous studies have shown that both vasoconstrictive peptide endothelin-1 (ET
      1) and inflammatory marker C-reactive protein (CRP) are implicated in the
      inflammatory process of atherosclerosis. The purpose of the present study was to
      observe effect of ET-1 on CRP production and the molecular mechanisms in rat
      vascular smooth muscle cells (VSMCs). The results showed that ET-1 was capable of
      stimulating VSMCs to produce CRP both in protein and in mRNA levels in vitro and
      in vivo. ET(A) receptor antagonist BQ123, but not ET(B) receptor antagonist
      BQ788, inhibited CRP production in VSMCs. In addition, ET-1 was able to elicit
      reactive oxygen species (ROS) generation and mitogen-activated protein kinase
      (MAPK) activation, and antioxidant pyrrolidine dithiocarbamate and p38MAPK
      inhibitor SB203580 inhibited ET-1-induced CRP expression. The results demonstrate
      that ET-1 induces CPR production in VSMCs via ET(A) receptor followed by ROS and
      MAPK signal pathway, which may contribute to better understanding of the role of
      ET-1 in inflammatory activation of the vessel wall during atherogenesis.

PMID- 19748489
TI  - Cyclic stretch induces cyclooxygenase-2 gene expression in vascular endothelial
      cells via activation of nuclear factor kappa-beta.
AB  - Vascular endothelial cells respond to biomechanical forces, such as cyclic
      stretch and shear stress, by altering gene expression. Since endothelial-derived
      prostanoids, such as prostacyclin and thromboxane A(2), are key mediators of
      endothelial function, we investigated the effects of cyclic stretch on the
      expression of genes in human umbilical vein endothelial cells controlling
      prostanoid synthesis: cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2),
      prostacyclin synthase (PGIS) and thromboxane A(2) synthase (TXAS). COX-2 and TXAS
      mRNAs were upregulated by cyclic stretch for 24h. In contrast, PGIS mRNA was
      decreased and stretch had no effect on COX-1 mRNA expression. We further show
      that stretch-induced upregulation of COX-2 is mediated by activation of the NF
      kappabeta signaling pathway.

PMID- 19748491
TI  - Exercise effects on activities of Na(+),K(+)-ATPase, acetylcholinesterase and
      adenine nucleotides hydrolysis in ovariectomized rats.
AB  - Hormone deficiency following ovariectomy causes activation of Na(+),K(+)-ATPase
      and acetylcholinesterase (AChE) that has been related to cognitive deficits in
      experimental animals. Considering that physical exercise presents neuroprotector
      effects, we decide to investigate whether exercise training would affect enzyme
      activation in hippocampus and cerebral cortex, as well as adenosine nucleotide
      hydrolysis in synaptosomes from cerebral cortex of ovariectomized rats. Female
      adult Wistar rats were assigned to one of the following groups: sham (submitted
      to surgery without removal of the ovaries), exercise, ovariectomized (Ovx) and
      Ovx plus exercise. Thirty days after surgery, animals were submitted to one month
      of exercise training, three times per week. After, rats were euthanized, blood
      serum was collected and hippocampus and cerebral cortex were dissected. Data
      demonstrated that exercise reversed the activation of Na(+),K(+)-ATPase and AChE
      activities both in hippocampus and cerebral cortex of ovariectomized rats.
      Ovariectomy decreased AMP hydrolysis in cerebral cortex and did not alter adenine
      nucleotides hydrolysis in blood serum. Exercise per se decreased ADP and AMP
      hydrolysis in cerebral cortex. On the other hand, AMP hydrolysis in blood serum
      was increased by exercise in ovariectomized adult rats. Present data support that
      physical exercise might have beneficial effects and constitute a therapeutic
      alternative to hormone replacement therapy for estrogen deprivation.

PMID- 19748490
TI  - Hypocretin/orexin in arousal and stress.
AB  - Multiple lines of evidence indicate that hypocretin/orexin (HCRT) participates in
      the regulation of arousal and arousal-related process. For example, HCRT axons
      and receptors are found within a variety of arousal-related systems. Moreover,
      when administered centrally, HCRT exerts robust wake-promoting actions. Finally,
      a dysregulation of HCRT neurotransmission is associated with the sleep/arousal
      disorder, narcolepsy. Combined, these observations suggested that HCRT might be a
      key transmitter system in the regulation of waking. Nonetheless, subsequent
      evidence indicates that HCRT may not play a prominent role in the initiation of
      normal waking. Instead HCRT may participate in a variety of processes such as
      consolidation of waking and/or coupling metabolic state with behavioral state.
      Additionally, substantial evidence suggests a potential involvement of HCRT in
      high-arousal conditions, including stress. Thus, HCRT neurotransmission is
      closely linked to high-arousal conditions, including stress, and HCRT
      administration exerts a variety of stress-like physiological and behavioral
      effects that are superimposed on HCRT-induced increases in arousal. Combined,
      this evidence suggests the hypothesis that HCRT may participate in behavioral
      responding under high-arousal aversive conditions. Importantly, these actions of
      HCRT may not be limited to stress. Like stress, appetitive conditions are
      associated with elevated arousal levels and a stress-like activation of various
      physiological systems. These and other observations suggest that HCRT may, at
      least in part, exert affectively neutral actions that are important under high
      arousal conditions associated with elevated motivation and/or need for action.

PMID- 19748492
TI  - Clioquinol inhibits NGF-induced Trk autophosphorylation and neurite outgrowth in
      PC12 cells.
AB  - Clioquinol is considered to be a causative agent of subacute myelo-optico
      neuropathy (SMON), although the pathogenesis of SMON is yet to be elucidated. To
      investigate the mechanism of neurotoxicity of clioquinol, we used PC12 cell line
      and focused on nerve growth factor (NGF) signaling through Trk receptor, which is
      essential for survival and differentiation of neuronal cells. Clioquinol
      inhibited NGF-induced Trk autophosphorylation in a dose-dependent manner. This
      inhibitory activity was further confirmed by the data of the inhibition of NGF
      induced mitogen-activated protein kinase (MAPK) phosphorylation, which is located
      in the down stream of NGF-Trk intracellular signaling pathway. Clioquinol also
      caused neurite retraction induced by NGF and cell death. NGF-stimulated
      (differentiated) cells were more vulnerable than naive cells. These results
      strongly suggest that clioquinol may cause the perturbation of the intracellular
      survival pathway by inhibiting Trk-initiated signaling pathway.

PMID- 19748494
TI  - Mithramycin protects against dopaminergic neurotoxicity in the mouse brain after
      administration of methamphetamine.
AB  - The present study was undertaken to examine the effects of mithramycin, an
      inhibitor of transcription factor Specificity protein (Sp)-1, on the behavioral
      changes and dopaminergic neurotoxicity in the mouse striatum after administration
      of methamphetamine (METH). Pretreatment with mithramycin (75, 150 or 300
      microg/kg) did not alter acute hyperlocomotion in mice after a single
      administration of METH (3 mg/kg). However, the development of behavioral
      sensitization in mice after repeated administration of METH (3 mg/kg/day, once
      daily for 5 days) was significantly blocked by pretreatment with mithramycin (300
      microg/kg). Furthermore, pretreatment with mithramycin (300 microg/kg)
      significantly attenuated the hyperthermia in mice after repeated administration
      of METH (3 mg/kgx3, 3-h intervals). Moreover, the combination of pretreatment and
      subsequent administration of mithramycin (75, 150 or 300 microg/kg) significantly
      attenuated the reductions of dopamine (DA), its major metabolite 3,4
      dihydroxyphenylacetic acid (DOPAC) and DA transporter (DAT) in the striatum after
      repeated administration of METH (3 mg/kgx3, 3-h intervals), and these
      attenuations were dose dependent. These findings suggest that mithramycin
      attenuates the development of behavioral sensitization and dopaminergic
      neurotoxicity in mice after repeated administration of METH. Therefore,
      mithramycin could have potential for the treatment of METH abusers, particularly
      since this drug has been approved by the Food and Drug Administration in the
      United States. In the future, however, another Sp1 inhibitors with fewer side
      effects might be more appropriate.

PMID- 19748493
TI  - Estrogen partially down-regulates PTEN to prevent apoptosis in VSC4.1 motoneurons
      following exposure to IFN-gamma.
AB  - PTEN is a tumor suppressor gene that is either mutated or deleted in a number of
      human cancers. PTEN acts as a negative regulator of the PI3K/Akt survival pathway
      and thus plays an important role in cell fate, proliferation, growth, and
      migration. Recent evidence suggests that PTEN may also be involved in the
      pathophysiology of neurodegenerative disorders such as spinal cord injury (SCI).
      Overexpression of PTEN appears to cause inactivation/dephosphorylation of Akt in
      neurons, resulting in increased cell death. Given this newly discovered role for
      PTEN, it has been identified as a potential molecular target for the development
      of novel therapeutic strategies against neurodegeneration. Motoneuron
      degeneration following SCI may occur due to up-regulation of pro-inflammatory and
      cytotoxic cytokines including IFN-gamma. Exposure of VSC4.1 motoneurons to IFN
      gamma (10 ng/ml) for 24 h resulted in significant overexpression of PTEN and
      decreased levels of activated Akt. Up-regulation of PTEN following IFN-gamma
      exposure was associated with decreased overall cell viability due to increased
      apoptosis, as assessed by Wright staining and analysis of cell death markers
      including Bax, Bcl-2, calpain activity, and caspase-3 activity, indicating a
      prominent role for PTEN in suppression of the PI3K/Akt survival pathway to
      promote motoneuron death. Addition of estrogen (100 nM) to VSC4.1 cells for 1 h
      prior to IFN-gamma exposure partially decreased PTEN expression, allowing
      adequate activation or phosphorylation of Akt (p-Akt) to prevent apoptotic cell
      death. Thus, it appears that estrogen may mediate neuroprotection through
      decrease in PTEN expression. In conclusion, our studies suggest that PTEN
      inactivation may be used as an important parameter for evaluation of the efficacy
      of estrogen in prevention of neuronal loss in neurodegenerative disorders.

PMID- 19748495
TI  - Impaired blood-brain and blood-spinal cord barriers in mutant SOD1-linked ALS
      rat.
AB  - Blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB) impairment is an
      additional accident occurring during the amyotrophic lateral sclerosis (ALS)
      progression. In this work, we aimed to decipher if BBB/BSCB leakage appeared
      before critical detrimental events and could serve as a marker preceding clinical
      symptoms. Three different BBB leakage markers: Evans blue, IgG and hemosiderin,
      were used to look at the SOD1-linked ALS rat model at presymptomatic and
      symptomatic stages. Although IgG and hemosiderin could be detected at
      presymptomatic stage, Evans blue extravasation which fits best with BBB/BSCB
      impairment could only be seen at symptomatic stages. BBB/BSCB impairment was
      further substantiate by showing at symptomatic stages decreased mRNA expression
      of ZO-1 and occludin as well as agrin, a basal membrane constituent. Electron
      microscopic data substantiate a toxic environment around endothelial cell and
      peri-vascular swollen astrocyte end-feet showing oedema-linked BBB opening.

PMID- 19748496
TI  - Purpurin is a key molecule for cell differentiation during the early development
      of zebrafish retina.
AB  - Recently, we cloned purpurin cDNA as an upregulated gene in the axotomized fish
      retina. The retina-specific protein was secreted from photoreceptors to ganglion
      cell layer during an early stage of optic nerve regeneration in zebrafish retina.
      The purpurin worked as a trigger molecule for axonal regrowth in adult injured
      fish retina. During zebrafish development, purpurin mRNA first appeared in
      ventral retina at 2 days post-fertilization (dpf) and spread out to the outer
      nuclear layer at 3 dpf. Here, we investigated the role of purpurin for zebrafish
      retinal development using morpholino gene knockdown technique. Injection of
      purpurin morpholino into the 1-2 cell stage of embryos significantly inhibited
      the transcriptional and translational expression of purpurin at 3 dpf. In the
      purpurin morphant, the eyeball was significantly smaller and retinal lamination
      of nuclear and plexiform layers was not formed at 3 dpf. Retinal cells of
      purpurin morphants were still proliferative and undifferentiated at 3 dpf. The
      visual function of purpurin morphant estimated by optomotor response was also
      suppressed at 5 dpf. By contrast, the control morphants with random sequence
      morpholino showed retinal lamination with distinct layers and differentiated
      cells at 3 dpf. These results strongly suggest that purpurin is a key molecule
      for not only optic nerve regeneration in adult but also cell differentiation
      during early development in embryo.

PMID- 19748497
TI  - Effects of treatments on inflammatory and apoptotic markers in the CNS of mice
      with globoid cell leukodystrophy.
AB  - Globoid cell leukodystrophy (GLD) or Krabbe disease is a neurodegenerative
      disorder caused by the deficiency of the lysosomal enzyme galactocerebrosidase
      (GALC). GALC deficiency results in a progressive demyelination of the central and
      peripheral nervous systems. Inflammatory cells and increased levels of cytokines
      and chemokines are present in the CNS of GLD mice and may play a significant role
      in the pathogenesis of the disease. In this study we evaluate the effect of non
      steroidal anti-inflammatory drugs, such as indomethacin and ibuprofen, and
      minocycline, a tetracycline analog with neuroprotective and anti-apoptotic
      properties, on the progression of the disease using a transgenic mouse model of
      GLD. Real-time quantitative PCR was used to analyze the expression of several
      markers of the immune/inflammatory response. IL-6, TNF-alpha, MIP-1beta, MCP-1,
      iNOS/NOS2, CD11b, CD68, CD4 and CD8 mRNA levels were measured in cortex,
      cerebellum and spinal cord of untreated and treated affected mice at different
      ages. In addition, the pharmacological treatments were compared to bone marrow
      transplantation (BMT). The pharmacological treatments significantly extended the
      life-span of the treated mice and reduced the levels of several of the immuno
      related factors studied. However, BMT produced the most dramatic improvements. In
      BMT-treated mice, factors in the spinal cord were normalized faster than the
      cerebellum, with the exception of CD68. There was a decrease in the number of
      apoptotic cells in the cerebellum of mice receiving anti-inflammatory drugs and
      BMT. These studies indicate a possible role for combined therapy in the treatment
      of GLD.

PMID- 19748498
TI  - Sympathetic innervation of the spleen in male Brown Norway rats: a longitudinal
      aging study.
AB  - Aging leads to reduced cellular immunity with consequent increased rates of
      infectious disease, cancer, and autoimmunity in the elderly. The sympathetic
      nervous system (SNS) modulates innate and adaptive immunity via innervation of
      lymphoid organs. In aged Fischer 344 (F344) rats, noradrenergic (NA) nerve
      density in secondary lymphoid organs declines, which may contribute to
      immunosenescence with aging. These studies suggest there is SNS involvement in
      age-induced immune dysregulation. The purpose of this study was to longitudinally
      characterize age-related change in sympathetic innervation of the spleen and
      sympathetic activity/tone in male Brown Norway (BN) rats, which live longer and
      have a strikingly different immune profile than F344 rats, the traditional animal
      model for aging research. Splenic sympathetic neurotransmission was evaluated
      between 8 and 32 months of age by assessing (1) NA nerve fiber density, (2)
      splenic norepinephrine (NE) concentration, and (3) circulating catecholamine
      levels after decapitation. We report a decline in NA nerve density in splenic
      white pulp (45%) at 15 months of age compared with 8-month-old (M) rats, which is
      followed by a much slower rate of decline between 24 and 32 months. Lower splenic
      NE concentrations between 15 and 32 months of age compared with 8M rats were
      consistent with morphometric findings. Circulating catecholamine levels after
      decapitation stress generally dropped with increasing age. These findings suggest
      there is a sympathetic-to-immune system dysregulation beginning at middle age.
      Given the unique T-helper-2 bias in BN rats, altered sympathetic-immune
      communication may be important for understanding the age-related rise in asthma
      and autoimmunity.

PMID- 19748499
TI  - Influence of dermal exposure to the pyrethroid insecticide deltamethrin on rat
      brain microanatomy and cholinergic/dopaminergic neurochemistry.
AB  - Deltamethrin is a pesticide largely used. Acute toxicity of this compound was
      extensively investigated, whereas less information is available on the effects of
      subchronic and/or chronic exposure to deltamethrin or on the effects of its
      dermal absorption. Sparse data are also available on deltamethrin neurotoxicity.
      This study has assessed in the rat the effects of dermal application of
      deltamethrin (30 mg/kg/day in cyclohexane for 4 weeks to the skin of the back of
      the neck) on microanatomy of cerebrocortical areas (frontal cortex and
      hippocampus) and on cholinergic and dopaminergic neurotransmission markers.
      Treatment with deltamethrin caused nerve cell loss and the appearance of signs of
      neuronal sufferance primarily in layer III of frontal cortex as well as in the
      dentate gyrus and to a lesser extent in the CA1 and CA3 subfields of hippocampus.
      Deltamethrin induced also astrogliosis. Cholinergic neurotransmission markers
      investigated in frontal cortex, hippocampus and striatum were acetylcholine
      (ACh), the synthesizing and catabolic enzymes choline acetyltransferase and
      acetylcholinesterase and the high affinity ACh uptake system labeled with
      [(3)H]hemicholinium-3. These markers were unaffected by deltamethrin
      administration. Dopamine and the dopamine plasma membrane transporter labeled
      with [(3)H]GBR 12935 were unaffected by treatment with deltamethrin in frontal
      cortex and decreased significantly in hippocampus and striatum. These findings
      indicate that dermal exposure to the pyrethroid insecticide deltamethrin using an
      administration module mimicking a possible long-lasting occupational skin contact
      is accompanied by cerebrocortical injury and loss of hippocampal and striatal
      dopamine and dopamine transporter. The sensitivity of dopaminergic system in our
      experimental model suggests that dermal exposure to deltamethrin could represent
      a risk factor for Parkinson's disease.

PMID- 19748500
TI  - Impact of quality control accepted inter-laboratory variations on calculated
      Fibrotest/Actitest scores for the non-invasive biochemical assessment of liver
      fibrosis.
AB  - INTRODUCTION: Non-invasive, i.e. serum-based assessment of liver fibrosis is
      still an important diagnostic challenge although multiple single and
      multiparametric panels of biomarkers have been suggested. AIM: Two approaches
      were followed to determine the diagnostic reliability of Fibrotest and Actitest,
      two commercially distributed non-invasive multiparametric tests for staging and
      grading of liver fibrosis. METHODS: (i) Haptoglobin, ALT, gamma GT, alpha-2
      macroglobulin, apolipoprotein A1 and bilirubin, required for calculation of
      respective scores, were determined in sera of 4 patients with histologically
      defined stages of fibrosis (F1-F4) and activities of fibrogenesis (A1-A3).
      Analytes were determined by 6 quality controlled external laboratories. Inter
      laboratory variations of the calculated Fibrotest score for staging and Actitest
      score for grading (BioPredictive), and their error ratios referred to histologic
      results were calculated. (ii) The variability of respective Fibrotest/Actitest
      scores depending on 64 selected combinations of analytes within the accepted
      ranges of analyte-specific maximum/minimum limits given by the external quality
      control of the German Association of Clinical Chemistry and Laboratory Medicine
      (DGKL) was calculated. RESULTS: (i) Fibrotest and Actitest scores were largely
      reproducible among the different laboratories. However, the error ratio was 77%
      for all results calculated by both, Fibrotest and Actitest when referred to
      histologic findings. (ii) Calculated scores of stages varied between F2 (9%), F3
      (31%), F3-F4 (6%), and F4 (54%) (Fibrotest), and A1/A2 (48%), A2 (9%), A2-A3
      (5%), and A3 (38%) for grades of fibrogenic activity. CONCLUSION: Despite
      reproducibility of Fibro- and Actitest scores among the six laboratories, large
      scale investigation displayed high levels of variability depending on inter
      laboratory differences that were still in a quality controlled, analytically
      acceptable range. Calculated scores coincided with histologic findings in less
      than 25% of all cases. Thus, the diagnostic accuracy of these tests must be
      considered as low, if histology is accepted as reference standard.

PMID- 19748501
TI  - MTHFR and TYMS genotypes influence TPMT activity and its differential modulation
      in males and females.
AB  - OBJECTIVES: TPMT catalyzes the deactivation of the cytostatic drug 6
      mercaptopurine used in treatment of cancer. Patients with low levels of TPMT more
      often experience severe toxic effects when treated with standard doses of 6
      mercaptopurine than patients with high levels who, in turn, may experience
      inadequate treatment. It is therefore very important to assess factors that could
      influence TPMT activity. DESIGN AND METHODS: Red blood cell TPMT activity was
      measured by means of HPLC and genotypes of 86 healthy individuals were analyzed
      using TaqMan and PCR-RFLP methods, in order to investigate the effect of TPMT,
      MTHFR and TYMS genotypes on TPMT activity. RESULTS: TPMT activity was higher in
      TPMT wild-type males than females (p=0.028). Three-way ANOVA interaction analysis
      revealed a significant interaction effect between MTHFR genotype and gender on
      TPMT activity (p=0.023). CONCLUSION: Males have higher TPMT activity than females
      and the trend of influence of MTHFR genotype on TPMT activity is different in the
      two gender groups.

PMID- 19748502
TI  - Sox10 promotes the survival of cochlear progenitors during the establishment of
      the organ of Corti.
AB  - Transcription factors of the SoxE family are critical players that underlie
      various embryological processes. However, little is known about their function
      during inner ear development. Here, we show that Sox10 is initially expressed
      throughout the otic vesicle epithelium and becomes later restricted to supporting
      cells as cell differentiation proceeds in the organ of Corti. Morphological
      analyses of Sox10 mutant mice reveal a significant shortening of the cochlear
      duct likely resulting from the progressive depletion of cochlear progenitors.
      While Sox10 appears dispensable for the differentiation and patterning of the
      inner ear prosensory progenitors, our data support a critical role for this
      transcription factor in the promotion of their survival. We provide genetic
      evidences that Sox10, in a concentration-dependant manner, could play a role in
      the regulation of Jagged1, a gene known to be important for inner ear prosensory
      development. Together, our results demonstrate that Sox10 regulates the biology
      of early cochlear progenitors during inner ear development, but, in contrast to
      neural crest-derived cells, this transcription factor is dispensable for their
      differentiation. Evidence also suggests that this effect occurs via the
      activation of the Jagged1 gene.

PMID- 19748503
TI  - Altered expression of aquaporins 1 and 4 coincides with neurodegenerative events
      in retinas of spontaneously diabetic Torii rats.
AB  - Evidence is mounting that not only microangiopathy, but also neurodegenerative
      events occur in the retinas of humans and rodents with early diabetes. Diverse
      pathologies are known to alter the amount and/or location of glial expression of
      the water-selective channels aquaporins (AQPs) 1 and 4. However, the temporal
      relationships among glial activation, the altered expression of the AQP proteins
      and neuronal death in the retinas of diabetic animals remains to be investigated.
      Male spontaneously diabetic Torii (SDT) rats reportedly develop diabetes by 40
      weeks of age at the latest and manifest proliferative diabetic retinopathy at 50
      weeks or later. This study compared temporal changes in neuroretinal apoptosis,
      glial fibrillary acidic protein (GFAP) expression and the expression of AQPs 1
      and 4 between SDT rat retinas and age-matched Sprague-Dawley (SD) rat retinas.
      Cell death was detected by terminal deoxynucleotidyl transferase-mediated deoxy
      uridine triphosphate nick end-labeling on retinal flatmounts and activated
      caspase 3 immunofluorescence of retinal cryosections. The expression of GFAP and
      AQPs 1 and 4 was assessed by immunohistochemistry of cryosections and retinal
      flatmounts. Diabetes started to develop around 15 weeks in SDT rats. Apoptotic
      cells in the ganglion cell layer and the inner nuclear layer were significantly
      more numerous in 40-week-old SDT rat retinas than in either age-matched SD rat
      retinas or 10-week-old SDT rats. GFAP immunoreactivity was confined to the nerve
      fiber layer both in SD and SDT rats at 10 weeks, whereas it spanned the whole
      retina in SDT rats, but not in SD rats, at 40 weeks. AQP1 was expressed in the
      outer retina, whereas AQP4 was expressed in the perivascular and end feet of
      Muller cells and astrocytes in the inner retina in the control SD rats and the
      SDT rats at 10 weeks. The perivascular AQPs shifted from AQP4 to AQP1 in 40-week
      old SDT rats that exhibited marked hyperglycemia. Thus, the development of
      diabetes increases neuroretinal apoptosis, and this coincides with an altered
      expression pattern of GFAP and water-selective channels AQPs 1 and 4 in SDT rats.

PMID- 19748504
TI  - PRMT-1 and DDAHs-induced ADMA upregulation is involved in ROS- and RAS-mediated
      diabetic retinopathy.
AB  - Asymmetric dimethylarginine (ADMA), an endogenous competitive inhibitor of nitric
      oxide synthase, is generated in presence of type 1 protein arginine N
      methyltransferase (PRMT-1) and is metabolized by dimethylarginine
      dimethylaminohydrolases (DDAHs). Reportedly ADMA is associated with endothelial
      dysfunction. The aim of this study is to investigate whether PRMT-1- and DDAHs
      induced ADMA increase in diabetic rat retina and high glucose-treated bovine
      retinal capillary endothelial cells (BRCECs) is involved in reactive oxygen
      species (ROS)- and renin-angiotensin system (RAS)-mediated diabetic retinopathy.
      Rats were divided into four groups: sham-injected group, streptozotocin (STZ)
      induced diabetic model group, STZ-induced diabetic model plus 12-week ACEI
      benazepril treatment group, and STZ-induced diabetic model plus 12-week ARB
      telmisartan treatment group. BRCECs were exposed to 5mM glucose, 30mM glucose,
      and 30mM glucose plus benazepril, telmisartan, diphenyliodonium (NADPH oxidase
      inhibitor, DPI), or N-Acetyl-l-cysteine (antioxidant and free radical scavenger,
      NAC) until passage four. We found that the concentrations of ADMA were
      significantly elevated in the plasma of diabetic rat models, and were
      significantly reduced by benazepril or telmisartan. DDAHs expression was
      decreased and PRMT-1 expression was increased in diabetic rat retina, which was
      reversed by benazepril. Telmisartan decreased PRMT-1 expression and increased
      DDAH II expression, but had no effect on DDAH I expression. In vitro, BRCECs
      exposed to high glucose had elevated ROS production, decreased cGMP, increased
      PRMT-1 expression, and decreased DDAH activity and DDAH II expression.
      Coincubating BRCECs with benazepril, telmisartan, DPI or NAC reversed the effects
      of high glucose. It can be concluded that PRMT-I and DDAHs-induced upregulation
      of ADMA levels might be involved in ROS- and RAS-mediated diabetic retinopathy.

PMID- 19748505
TI  - Corneal confocal microscopy: a novel means to detect nerve fibre damage in
      idiopathic small fibre neuropathy.
AB  - Patients with idiopathic small fibre neuropathy (ISFN) have been shown to have
      significant intraepidermal nerve fibre loss and an increased prevalence of
      impaired glucose tolerance (IGT). It has been suggested that the dysglycemia of
      IGT and additional metabolic risk factors may contribute to small nerve fibre
      damage in these patients. Twenty-five patients with ISFN and 12 aged-matched
      control subjects underwent a detailed evaluation of neuropathic symptoms,
      neurological deficits (Neuropathy deficit score (NDS); Nerve Conduction Studies
      (NCS); Quantitative Sensory Testing (QST) and Corneal Confocal Microscopy (CCM))
      to quantify small nerve fibre pathology. Eight (32%) patients had IGT. Whilst all
      patients with ISFN had significant neuropathic symptoms, NDS, NCS and QST except
      for warm thresholds were normal. Corneal sensitivity was reduced and CCM
      demonstrated a significant reduction in corneal nerve fibre density (NFD)
      (P<0.0001), nerve branch density (NBD) (P<0.0001), nerve fibre length (NFL)
      (P<0.0001) and an increase in nerve fibre tortuosity (NFT) (P<0.0001). However
      these parameters did not differ between ISFN patients with and without IGT, nor
      did they correlate with BMI, lipids and blood pressure. Corneal confocal
      microscopy provides a sensitive non-invasive means to detect small nerve fibre
      damage in patients with ISFN and metabolic abnormalities do not relate to nerve
      damage.

PMID- 19748506
TI  - In search for a common denominator for the diverse functions of arthropod
      corazonin: a role in the physiology of stress?
AB  - Corazonin (Crz) is an 11 amino acid C-terminally amidated neuropeptide that has
      been identified in most arthropods examined with the notable exception of beetles
      and an aphid. The Crz-receptor shares sequence similarity to the GnRH-AKH
      receptor family thus suggesting an ancestral function related to the control of
      reproduction and metabolism. In 1989, Crz was purified and identified as a potent
      cardioaccelerating agent in cockroaches (hence the Crz name based on "corazon",
      the Spanish word for "heart"). Since the initial assignment as a
      cardioacceleratory peptide, additional functions have been discovered, ranging
      from pigment migration in the integument of crustaceans and in the eye of
      locusts, melanization of the locust cuticle, ecdysis initiation and in various
      aspects of gregarization in locusts. The high degree of structural conservation
      of Crz, its well-conserved (immuno)-localization, mainly in specific
      neurosecretory cells in the pars lateralis, and its many functions, suggest that
      Crz is vital. Yet, Crz-deficient insects develop normally. Upon reexamining all
      known effects of Crz, a hypothesis was developed that the evolutionary ancient
      function of Crz may have been "to prepare animals for coping with the
      environmental stressors of the day". This function would then complement the role
      of pigment-dispersing factor (PDF), the prime hormonal effector of the clock,
      which is thought "to set a coping mechanism for the night".

PMID- 19748507
TI  - Density and maturation of rodlet cells in brain tissue of fathead minnows
      (Pimephales promelas) exposed to trematode cercariae.
AB  - Evidence for the presumed linkage between the enigmatic rodlet cells of fish and
      exposure to helminths is anecdotal and indirect. We evaluated the proliferation
      and development of rodlet cells in the optic lobes of fathead minnows exposed to
      cercariae of Ornithodiplostomum ptychocheilus. Mean rodlet cell densities (ca.
      10/mm(2)) in the optic lobes were similar between unexposed controls and minnows
      with 1- and 2-week old infections. Rodlet cell densities increased at 4 weeks
      p.i., reaching maxima (ca. 200/mm(2)) at 6 weeks p.i., followed by a decline at 9
      weeks. This temporal pattern of proliferation and maturation paralleled the
      development of metacercariae within the optic lobes. Unencysted metacercariae
      develop rapidly within tissues of the optic lobes for approximately 4 weeks after
      penetration by cercariae, then shift to the adjacent meninges to encyst. The
      former stage is associated with tissue damage, the latter with massive
      inflammation of the meninges. Thus, peak densities and maturation of rodlet cells
      correspond to the period when inflammation of the meninges caused by the large
      metacercarial cysts is at a maximum. Our results support recent contentions that
      rodlet cells comprise part of the host inflammatory defence response.

PMID- 19748508
TI  - Validity of multiplex-based assays for cytokine measurements in serum and plasma
      from "non-diseased" subjects: comparison with ELISA.
AB  - Multiplex-based immunoassays (MIA) allow the simultaneous measurement of
      different cytokines in small sample volumes, but their applicability in samples
      from "healthy" subjects, as those participating in large-scale epidemiological
      studies is not well known. We compared measurements of interleukin-6 (IL-6),
      tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta),
      interleukin-1 receptor antagonist (IL-1Ra), C-reactive protein (CRP) and soluble
      CD40L (sCD40L) obtained by MIA with those obtained by enzyme-linked immunosorbent
      assays (ELISA) in serum and plasma samples from 36 "healthy" subjects. We
      observed good correlations between measurements obtained by MIA and ELISA for IL
      1Ra, CRP and sCD40L (r>0.80) but poor correlations for IL-6, TNF-alpha and IL
      1beta (r<0.40). When comparing MIA plasma and serum measurements, very high
      correlations were obtained for CRP (r=0.98) and fairly good correlations for IL
      1Ra (r=0.60). In conclusion, multiplex-based assays can give an accurate estimate
      of the relative risk in large-scale epidemiological studies but only for
      cytokines that are present in relatively large concentrations (ng/mL).

PMID- 19748509
TI  - The molecular organization of the fungal prion HET-s in its amyloid form.
AB  - The prion hypothesis states that it is solely the three-dimensional structure of
      the polypeptide chain that distinguishes the prion and nonprion forms of the
      protein. For HET-s, the atomic-resolution structure of the isolated prion domain
      HET-s(218-289), consisting of a highly ordered triangular cross-beta arrangement,
      is known. Here we present a solid-state NMR study of fibrils of the full-length
      HET-s prion in which we compare their spectra with spectra from isolated C
      terminal prion domain fibrils and the crystalline N-terminal globular domain HET
      s(1-227). The spectra reveal unequivocally that the highly ordered structure of
      the isolated prion domain HET-s(218-289) is conserved in the context of the full
      length fibrils investigated here. However, the globular domain loses much of its
      tertiary structure while partly retaining its secondary structure, thus
      exhibiting behavior reminiscent of a molten globule. Flexible residues that may
      constitute the linker connecting the two domains are detected using INEPT
      (insensitive nuclei enhanced by polarization transfer) spectroscopy. Based on our
      data, we propose a structural model that is in line with a general model
      developed for amyloid fibrils built from a cross-beta core decorated with
      globular domains. The loss of structure in the HET-s globular domain sharply
      contrasts with the behavior observed for fibrils of Ure2p and suggests that there
      is considerable structural diversity in the fibrils of globular-domain-containing
      prions despite their similar appearances at the microscopic level.

PMID- 19748510
TI  - Stabilization of the tertiary structure of the cholera toxin A1 subunit inhibits
      toxin dislocation and cellular intoxication.
AB  - Cholera toxin (CT) moves from the cell surface to the endoplasmic reticulum (ER)
      by retrograde vesicular transport. The catalytic subunit of CT (CTA1) then
      crosses the ER membrane and enters the cytosol in a process that involves the
      quality control mechanism of ER-associated degradation. The molecular details of
      this dislocation event have not been fully characterized. Here, we report that
      thermal instability in the CTA1 subunit-specifically, the loss of CTA1 tertiary
      structure at 37 degrees C-triggers toxin dislocation. Biophysical studies found
      that glycerol preferentially stabilized the tertiary structure of CTA1 without
      having any noticeable effect on the thermal stability of its secondary structure.
      The thermal disordering of CTA1 tertiary structure normally preceded the
      perturbation of its secondary structure, but in the presence of 10% glycerol the
      temperature-induced loss of CTA1 tertiary structure occurred at higher
      temperatures in tandem with the loss of CTA1 secondary structure. The glycerol
      induced stabilization of CTA1 tertiary structure blocked CTA1 dislocation from
      the ER and instead promoted CTA1 secretion into the extracellular medium. This,
      in turn, inhibited CT intoxication. Glycerol treatment also inhibited the in
      vitro degradation of CTA1 by the core 20S proteasome. Collectively, these
      findings indicate that toxin thermal instability plays a key role in the
      intoxication process. They also suggest the stabilization of CTA1 tertiary
      structure is a potential goal for novel antitoxin therapeutic agents.

PMID- 19748512
TI  - Prion fibrils of Ure2p assembled under physiological conditions contain highly
      ordered, natively folded modules.
AB  - The difference between the prion and the non-prion form of a protein is given
      solely by its three-dimensional structure, according to the prion hypothesis. It
      has been shown that solid-state NMR can unravel the atomic-resolution three
      dimensional structure of prion fragments but, in the case of Ure2p, no highly
      resolved spectra are obtained from the isolated prion domain. Here, we
      demonstrate that the spectra of full-length fibrils of Ure2p interestingly lead
      to highly resolved solid-state NMR spectra. Prion fibrils formed under
      physiological conditions are therefore well-ordered objects on the molecular
      level. Comparing the full-length NMR spectra with the corresponding spectra of
      the prion and globular domains in isolation reveals that the globular part in
      particular shows almost perfect structural order. The NMR linewidths in these
      spectra are as narrow as the ones observed in crystals of the isolated globular
      domain. For the prion domain, the spectra reflect partial disorder, suggesting
      structural heterogeneity, both in isolation and in full-length Ure2p fibrils,
      although to different extents. The spectral quality is surprising in the light of
      existing structural models for Ure2p and in comparison to the corresponding
      spectra of the only other full-length prion fibrils (HET-s) investigated so far.
      This opens the exciting perspective of an atomic-resolution structure
      determination of the fibrillar form of a prion whose assembly is not accompanied
      by significant conformational changes and documents the structural diversity
      underlying prion propagation.

PMID- 19748511
TI  - Novel isoform-specific interfaces revealed by PKA RIIbeta holoenzyme structures.
AB  - The cAMP-dependent protein kinase catalytic (C) subunit is inhibited by two
      classes of functionally nonredundant regulatory (R) subunits, RI and RII. Unlike
      RI subunits, RII subunits are both substrates and inhibitors. Because RIIbeta
      knockout mice have important disease phenotypes, the RIIbeta holoenzyme is a
      target for developing isoform-specific agonists and/or antagonists. We also know
      little about the linker region that connects the inhibitor site to the N-terminal
      dimerization domain, although this linker determines the unique globular
      architecture of the RIIbeta holoenzyme. To understand how RIIbeta functions as
      both an inhibitor and a substrate and to elucidate the structural role of the
      linker, we engineered different RIIbeta constructs. In the absence of nucleotide,
      RIIbeta(108-268), which contains a single cyclic nucleotide binding domain, bound
      C subunit poorly, whereas with AMP-PNP, a non-hydrolyzable ATP analog, the
      affinity was 11 nM. The RIIbeta(108-268) holoenzyme structure (1.62 A) with AMP
      PNP/Mn(2+) showed that we trapped the RIIbeta subunit in an enzyme:substrate
      complex with the C subunit in a closed conformation. The enhanced affinity
      afforded by AMP-PNP/Mn(2+) may be a useful strategy for increasing affinity and
      trapping other protein substrates with their cognate protein kinase. Because
      mutagenesis predicted that the region N-terminal to the inhibitor site might dock
      differently to RI and RII, we also engineered RIIbeta(102-265), which contained
      six additional linker residues. The additional linker residues in RIIbeta(102
      265) increased the affinity to 1.6 nM, suggesting that docking to this surface
      may also enhance catalytic efficiency. In the corresponding holoenzyme structure,
      this linker docks as an extended strand onto the surface of the large lobe. This
      hydrophobic pocket, formed by the alphaF-alphaG loop and conserved in many
      protein kinases, also provides a docking site for the amphipathic helix of PKI.
      This novel orientation of the linker peptide provides the first clues as to how
      this region contributes to the unique organization of the RIIbeta holoenzyme.

PMID- 19748513
TI  - Relationship between protein stabilization and protein rigidification induced by
      mannosylglycerate.
AB  - Understanding protein stabilization by small organic compounds is a topic of
      great practical importance. The effect of mannosylglycerate, a charged compatible
      solute typical of thermophilic microorganisms, on a variant of staphylococcal
      nuclease was investigated using several NMR spectroscopy methods. No structural
      changes were apparent from the chemical shifts of amide protons. Measurements of
      (15)N relaxation and model-free analysis, water-amide saturation transfer (phase
      modulated CLEAN chemical exchange), and hydrogen/deuterium exchange rates
      provided a detailed picture of the effects of mannosylglycerate on the backbone
      dynamics and time-averaged structure of this protein. The widest movements of the
      protein backbone were significantly constrained in the presence of
      mannosylglycerate, as indicated by the average 5-fold decrease of the
      hydrogen/deuterium exchange rates, but the effect on the millisecond timescale
      was small. At high frequencies, internal motions of staphylococcal nuclease were
      progressively restricted with increasing concentrations of mannosylglycerate or
      reduced temperature, while the opposite effect was observed with urea (a
      destabilizing solute). The order parameters showed a strong correlation with the
      changes in the T(m) values induced by different solutes, determined by
      differential scanning calorimetry. These data show that mannosylglycerate caused
      a generalised reduction of backbone motions and demonstrate a correlation between
      protein stabilization and protein rigidification.

PMID- 19748514
TI  - Activated astroglia during chronic inflammation in Alzheimer's disease--do they
      neglect their neurosupportive roles?
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder, characterized
      histopathologically by the extracellular deposition of beta-amyloid peptide in
      senile plaques, as well as intracellular neurofibrillary tangles (NFT) of
      hyperphosphorylated tau protein, extensive neuronal loss and synaptic changes in
      the hippocampus and cerebral cortex. In addition, the AD brain shows chronic
      inflammation characterized by an abundance of reactive astrocytes and activated
      microglia. In the healthy brain, astrocytes provide essential services for brain
      homeostasis and neuronal function, including metabolic support for neurons in the
      form of lactate, glutamate uptake and conversion into glutamine, and synthesis of
      glutathione and its precursors. In AD, a large body of evidence now suggests that
      by transforming from a basal to a reactive state, astrocytes neglect their
      neurosupportive functions, thus rendering neurons vulnerable to neurotoxins
      including pro-inflammatory cytokines and reactive oxygen species. This review
      will explain the normal functions of astrocytes, and how these cells might be
      activated to turn into inflammatory cells, actively contributing to
      neurodegeneration and neglecting their neurosupportive roles ("neuro-neglect
      hypothesis"). Furthermore, it is proposed that astrocytes might be promising
      target of therapeutic intervention for Alzheimer's disease, if these compromised
      functions can be normalized with pharmacological agents that are specifically
      designed to return astrocytes to a quiescent phenotype or supplement factors
      which activated astrocytes lack to produce.

PMID- 19748515
TI  - Behavioural and neurochemical abnormalities in mice lacking functional tachykinin
      1 (NK1) receptors: a model of attention deficit hyperactivity disorder.
AB  - In rodent behavioural screens, such as the forced swim or resident/intruder
      tests, the behaviour of mice that lack functional substance P-preferring,
      tachykinin-1 receptors ((NK1R) either through drug antagonism or gene ablation)
      mimics that of wildtype mice that have been treated with an antidepressant drug.
      All antidepressants modify the function of monoamine-releasing neurones in the
      brain. Our intention was to investigate whether monoaminergic transmission in
      NK1R-/- mice resembles that of wildtypes given an antidepressant. In the course
      of this work, we discovered that NK1R-/- mice express locomotor hyperactivity
      that is prevented by psychostimulants (d-amphetamine or methylphenidate).
      Moreover, hyperactivity is induced in wildtypes by treating them with an NK1R
      antagonist (at doses that have no effect on the behaviour of NK1R-/- mice): this
      hyperactivity is prevented by d-amphetamine, as in NK1R-/- mice. The mutant mice
      display several other abnormalities, which affect their behaviour and central
      monoaminergic transmission. These include: increased release of noradrenaline and
      a deficit in dopaminergic transmission in the prefrontal cortex
      ('hypofrontality'); a lack of an increase in dopamine efflux in the dorsal
      striatum following systemic administration of d-amphetamine; and a lack of
      development of d-amphetamine or morphine-induced conditioned place preference.
      Collectively, these findings strongly parallel abnormalities expressed by
      patients with Attention Deficit Hyperactivity Disorder (ADHD) and suggest that
      NK1R-/- mice offer a novel model of this disorder. We propose that mutations in
      the NK1R gene (tacr1 in humans) could contribute to this disorder, and that drugs
      that activate NK1R could offer therapeutic relief.

PMID- 19748516
TI  - Decision making under ambiguity and under risk in mesial temporal lobe epilepsy.
AB  - Decision making is essential in everyday life. Though the importance of the
      mesial temporal lobe in emotional processing and feedback learning is generally
      recognized, decision making in mesial temporal lobe epilepsy (mTLE) is almost
      unexplored so far. Twenty-eight consecutive epilepsy patients with drug resistant
      mTLE and fifty healthy controls performed decision tasks under initial ambiguity
      (participants have to learn by feedback to make advantageous decisions) and under
      risk (advantageous choices may be made by estimating risks and by rational
      strategies). A subgroup analysis compared the performance of patients affected by
      MRI-verified abnormalities of the hippocampus or amygdala. The effect of lesion
      side was also assessed. In decision under ambiguity, mTLE patients showed marked
      deficits and did not improve over the task. Patients with hippocampus abnormality
      and patients with amygdala abnormality showed comparable deficits. No difference
      was found between right and left TLE groups. In decision under risk, mTLE
      patients performed at the same level as controls. Results suggest that mTLE
      patients have difficulties in learning from feedback and in making decisions in
      uncertain, ambiguous situations. By contrast, they are able to make advantageous
      decisions when full information is given and risks, possible gains and losses are
      exactly defined.

PMID- 19748517
TI  - Characteristics of the control of human thermoregulatory behavior.
AB  - The aim of this study was to characterize several of the thermal input(s) that
      influence thermo-behavior in humans. Eight male subjects completed two trials in
      which they were free to initiate an exit from a hot chamber (45 degrees C) to a
      cold chamber (10 degrees C; H-->C) or from a cold chamber to a hot chamber (C-
      >H). Upon initiating an exit from the chamber, mean skin temperature (T(Sk)),
      rectal temperature (T(Rectal)), subjective thermal comfort, and time in the
      climate chambers prior to exit were recorded. Thermo-behavior was defined as the
      initiation of exit. All variables were similar (P> or =0.05) between the two
      trials. T(Sk) and thermal comfort at H-->C were significantly (P</=0.05) higher
      (34.0+/-1.1 degrees C, and 7.3+/-0.6, respectively) than at C-->H (29.4+/-0.9
      degrees C, and 3.0+/-0.6, respectively). No significant differences (P> or =0.05)
      were found between H-->C and C-->H for T(Rectal) (H-->C: 37.0+/-0.2 degrees C vs.
      C-->H: 37.0+/-0.2 degrees C) or time prior to exit (H-->C: 3.9+/-2.3 min vs. C-
      >H: 3.9+/-1.7 min). The frequency distributions and the probability of the
      initiation of exit curves at H-->C and C-->H for both T(Sk) and thermal comfort
      were significantly negatively skewed (P< or =0.05) and normally distributed,
      respectively (P>/=0.05). Skin temperature appears to be an important thermal
      input mediating thermo-behavioral responses. This behavioral response appears to
      be more precise when exposed to hot temperatures compared to cold temperatures.

PMID- 19748518
TI  - Synthesis of "glycospirostanes" via ring-closing metathesis.
AB  - Syntheses of "glycospirostanes" from 3beta-hydroxy-23,24-dinor-5alpha-cholano
      22,16-lactone and 3alpha-hydroxy-23,24-dinor-5beta-cholano-22,16-lactone were
      performed. The key step of these syntheses was ring-closing metathesis of the
      corresponding C,O-diallyl derivative. Further elaboration of the six-membered
      ring F consisted of allylic hydroxylation with SeO(2) followed by OsO(4)
      dihydroxylation of the C24-C25 double bond. The obtained final products proved to
      be simultaneously O- and C-l-arabinopyranosides.

PMID- 19748519
TI  - Comparative functional observational battery study of twelve commercial
      pyrethroid insecticides in male rats following acute oral exposure.
AB  - Twelve commercial pyrethroid insecticides (technical-grade active ingredients)
      were evaluated individually for acute neurobehavioral manifestations of toxicity
      under conditions suited to assist with determining whether they act by a common
      mechanism of toxicity. The pyrethroids that were tested reflect a diversity of
      structures, including six with an alpha-cyano phenoxybenzyl moiety (beta
      cyfluthrin, lambda-cyhalothrin, cypermethrin, deltamethrin, esfenvalerate and
      fenpropathrin) and six without this moiety (bifenthrin, S-bioallethrin,
      permethrin, pyrethrins, resmethrin and tefluthrin). These chemicals also present
      a variety of behavioral effects, including ones that are historically classified
      as causing a T (tremor), CS (choreoathetosis with salivation) or intermediate
      syndrome of intoxication, and others that have not previously been classified.
      Each pyrethroid that was tested consisted of the complement of isomers that occur
      in commercial products--a key factor for relevance for environmental and human
      exposure and for comparisons, since the biological activity of the individual
      isomers can vary tremendously. Young-adult male Sprague-Dawley rats (10 per dose
      group) were administered a single dose of pyrethroid by oral gavage, in corn oil,
      at a volume of 5 ml/kg. Each was tested at a range of two or three dose levels,
      including a minimally toxic dose, to establish the more sensitive manifestations
      of toxicity, and a more toxic dose, to establish a more complete spectrum of
      neurobehavioral manifestations. Animals were evaluated using a functional
      observational battery (FOB) that was designed to characterize and distinguish
      effects classically associated with T or CS syndromes of intoxication. The FOB
      was performed when manifestations of toxicity were most apparent at the time of
      peak effect (2, 4, or 8 h post-dosing) by observers who were blinded to dose
      group assignment, thus avoiding possible bias. The results from this study
      indicate that some pyrethroids clearly exhibit the historic classification
      symptoms of the T and CS syndromes while others do so less obviously. Use of the
      statistical technique of Principal Component Analysis (PCA) further helped
      interpret the study findings, as described in the accompanying paper
      (Breckenridge et al., 2009). These results establish manifestations of
      neurotoxicity in vivo that can be used as weight of evidence to determine whether
      pyrethroid insecticides act through a common mechanism of toxicity in mammals.
      Based on a review of the FOB data, analyzed by PCA, and other published data, two
      common mechanism groups are proposed. Group 1 would include pyrethrins,
      bifenthrin, resmethrin, permethrin, S-bioallethrin and tefluthrin. Group 2 would
      include cypermethrin, deltamethrin, esfenvalerate, beta-cyfluthrin and lambda
      cyhalothrin. Fenpropathrin exhibited features of both groups.

PMID- 19748520
TI  - Improving diagnosis of central venous catheter-related bloodstream infection by
      using differential time to positivity as a hospital-wide approach at a cancer
      hospital.
AB  - OBJECTIVES: Considering the difficulty of diagnosing catheter-related bloodstream
      infection (CRBSI), Koo Foundation Sun Yat-Sen Cancer Center uses differential
      time to positivity (DTP) as a hospital-wide approach to improve the diagnosis of
      CRBSI in febrile patients with indwelling central venous catheters (CVCs). This
      study describes the result of a hospital-wide use of DTP in a real practice
      setting. METHODS: During January 2003-August 2007, 142 positive paired blood
      cultures from 125 patients without infection focus other than CVC were included.
      These were evaluated by DTP and semi-quantitative catheter culture (SQCC) to
      confirm the diagnosis of CRBSI, and were further divided into two groups:
      confirmed (either by DTP or SQCC) and non-confirmed CRBSI (neither DTP nor SQCC
      positive). RESULTS: Fifty-nine point two percent (84/142) of episodes were
      confirmed as CRBSI, of which DTP was positive in 83.3% (n=70). Non-confirmed
      CRBSI was associated with hematologic malignancy, neutropenia status, previous
      antibiotics exposure and a lower CVC removal rate. CONCLUSIONS: A hospital-wide
      approach of DTP was practical and feasible in improving the diagnosis of CRBSI in
      a real practice setting.

PMID- 19748521
TI  - The virulence variability of different Acinetobacter baumannii strains in
      experimental pneumonia.
AB  - OBJECTIVES: Our objective was to compare the virulence of 5 strains of
      Acinetobacter baumannii by using a mouse model of pneumonia. METHODS: Six-week
      old female C3H/HeN mice were used. The pneumonia was inducted by intra-tracheal
      inoculation of 5.10(6) bacteria. Spontaneous outcome was evaluated by mortality,
      mice weight variations, and a clinical score. Bacterial counts in lungs, spleen
      and blood, and inflammatory response in lungs (dosages of tumor necrosis factor
      alpha and macrophage inflammatory protein-2) were also measured. Lastly, a
      histological examination of lungs was performed for 3 strains, giving a
      histological score. RESULTS: Global mortality varied from 13% to 79% (P<10(-4)).
      Bacterial counts in lungs within the 4 days following inoculation varied
      significantly according to different strains. The evolution curves of bacterial
      counts were also different. There was a significant correlation between the
      clinical score and mortality (P<0.05) but not between bacterial counts in lungs
      and mortality. The increase of pro-inflammatory mediator production in lungs and
      the histological score also varied according to strains. CONCLUSIONS: These
      results demonstrate the variability of the virulence between strains, and suggest
      that bacterial proliferation is not the only virulence factor responsible for the
      pathogenesis in A. baumannii pneumonia.

PMID- 19748522
TI  - Proteomic analysis of microdissected facial nuclei of the rat following facial
      nerve injury.
AB  - Recent studies using molecular and genetic techniques just have started to
      elucidate the complex process that drives successful peripheral nerve
      regeneration. Introducing proteomics to this field, we unilaterally performed a
      facial nerve axotomy in 13 adult Wistar rats. Seven days later, a total of 40 20
      microm coronary cryostat sections of the operated and contralateral unoperated
      nucleus facialis were microdissected. On the one hand, microdissected areas were
      pooled for each side, lysed and applied to ProteinChip Arrays. On the other hand,
      one microdissected area from the right and left facial nucleus each was directly
      placed on the affinity chromatographic array. Facial motoneurons were lysed in
      situ and released their proteins to spatially defined points. 215 laser
      addressable distinct positions across the surface of the spot enabled a high
      spatial resolution of measured protein profiles for the analysed tissue area.
      Protein profiles of the single positions were plotted over the used tissue
      section to visualize their distribution. The comparative analysis of the protein
      lysates from operated and normal nuclei facialis revealed, for both approaches
      used, differentially expressed proteins. Although by direct application of one
      cryostat section only a few hundred motoneurons were analysed, results comparable
      to these using lysates were obtained. Additionally, the applied technique
      revealed differences in the intensity distribution of several proteins of unknown
      function in the lesioned in comparison to the contralateral normal facial
      nucleus. This proteomic analysis with ultra high sensitivity paired with
      potential for a spatial resolution is a promising methodology for peripheral
      nerve regeneration studies.

PMID- 19748523
TI  - Utility of RNAi-mediated prnp gene silencing in neuroblastoma cells permanently
      infected by prions: potentials and limitations.
AB  - Prion diseases are incurable, transmissible neurodegenerative disorders in humans
      and animals. Because the disease-associated isoform of prion protein, PrP(Sc), is
      conformationally converted from cellular prion protein, PrP(C), knockdown of
      PrP(C) expression by RNA interference (RNAi) implicates therapy for prion
      diseases. In this study, introduction of small interfering (si) and small hairpin
      (sh) RNAs targeting the prion protein gene (prnp) transcripts triggered specific
      gene silencing and reduced the PrP(C) level in both prion-free and -infected
      neuroblastoma cell lines. Furthermore, this approach suppressed PrP(Sc) formation
      and ultimately eliminated PrP(Sc) from prion-infected cell lines. However,
      prolonged culture of cured cells resulted in reappearance of PrP(Sc) in the cell
      population, presumably by de novo PrP(Sc) formation from residual PrP(C)
      uncontrolled by RNAi and PrP(Sc) remained under the detection limit. Protein
      misfolding cyclic amplification assays further confirmed that lysate of cured
      cells was sufficient to support PrP(Sc) propagation. Our data not only suggest a
      potential treatment option but also implicate a caveat for using an RNAi approach
      for prion diseases. These findings provide critical information required to
      advance RNAi-based prevention and therapy for prion diseases of humans and
      animals.

PMID- 19748524
TI  - Efficient induction of cytotoxic T lymphocytes specific for severe acute
      respiratory syndrome (SARS)-associated coronavirus by immunization with surface
      linked liposomal peptides derived from a non-structural polyprotein 1a.
AB  - Spike and nucleocapsid are structural proteins of severe acute respiratory
      syndrome (SARS)-associated coronavirus (SARS-CoV) and major targets for cytotoxic
      T lymphocytes (CTLs). In contrast, non-structural proteins encoded by two-thirds
      of viral genome are poorly characterized for cell-mediated immunity. We
      previously demonstrated that nucleocapsid-derived peptides chemically coupled to
      the surface of liposomes effectively elicited SARS-CoV-specific CTLs in mice.
      Here, we attempted to identify HLA-A*0201-restricted CTL epitopes derived from a
      non-structural polyprotein 1a (pp1a) of SARS-CoV, and investigated whether
      liposomal peptides derived from pp1a were effective for CTL induction. Out of 30
      peptides predicted on computational algorithms, nine peptides could significantly
      induce interferon gamma (IFN-gamma)-producing CD8(+) T cells in mice. These
      peptides were coupled to the surface of liposomes, and inoculated into mice. Six
      liposomal peptides effectively induced IFN-gamma-producing CD8(+) T cells and
      seven liposomal peptides including the six peptides primed CTLs showing in vivo
      killing activities. Further, CTLs induced by the seven liposomal peptides lysed
      an HLA-A*0201 positive cell line expressing naturally processed, pp1a-derived
      peptides. Of note, one of the liposomal peptides induced high numbers of long
      lasting memory CTLs. These data suggest that surface-linked liposomal peptides
      derived from pp1a might offer an efficient CTL-based vaccine against SARS.

PMID- 19748525
TI  - Genetic validation of aldolase and glyceraldehyde-3-phosphate dehydrogenase as
      drug targets in Trypanosoma brucei.
AB  - Aldolase (ALD) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) of
      Trypanosoma brucei are considered to be promising targets for chemotherapeutic
      treatment of African sleeping sickness, because glycolysis is the single source
      of ATP for the parasite when living in the human bloodstream. Moreover, these
      enzymes appeared to possess distinct kinetic and structural properties that have
      already been exploited for the discovery of effective and selective inhibitors
      with trypanocidal activity. Here we present an experimental, quantitative
      assessment of the importance of these enzymes for the glycolytic pathway. This
      was achieved by decreasing the concentrations of ALD and GAPDH by RNA
      interference. The effects of these knockdowns on parasite growth, levels of
      various enzymes and transcripts, enzyme activities and glucose consumption were
      studied. A partial depletion of ALD and GAPDH was already sufficient to rapidly
      kill the trypanosomes. An effect was also observed on the activity of some other
      glycolytic enzymes.

PMID- 19748526
TI  - The role of G-proteins in the dimerisation of human somatostatin receptor types 2
      and 5.
AB  - Somatostatin (SST) is a peptide hormone that acts through a family of
      heptahelical receptors belonging to the G-protein coupled receptor (GPCR)
      superfamily. There are five known SST receptor subtypes termed SSTR1-5 and all
      couple to G alpha(i/o) G-proteins. It has been previously demonstrated that these
      receptors can form both homo- and heterodimers within their family or with other
      GPCR family members. Although agonist was demonstrated as a factor in modulating
      certain dimeric pairs, the molecular mechanism(s) underlying this regulation
      remains undetermined. Here, we demonstrate the coupling of G-protein as a
      contributing factor in the homo- and heterodimerisation of human (h) SSTR2 and
      SSTR5. When cells stably expressing hSSTR2 are pretreated with pertussis toxin
      (PTX), dissociation of hSSTR2 dimers occurs. Interestingly, although dimerisation
      of hSSTR5 was unaffected following PTX treatment, heterodimerisation between
      hSSTR2 and hSSTR5 is potentiated in the absence of receptor-stimulation. These
      results demonstrate the importance of G-protein in the maintenance and regulation
      of hSSTR dimers.

PMID- 19748527
TI  - Angiotensin II activates JAK2/STAT3 pathway and induces interleukin-6 production
      in cultured rat brainstem astrocytes.
AB  - We have shown that tyrosine kinases and mitogen-activated protein kinases mediate
      angiotensin II (Ang II) effects in cultured rat astrocytes. In this study, we
      investigated whether Ang II induces Janus kinase (JAK) 2, signal transducer and
      activators of transcription (STAT) 3 phosphorylation, and interleukin-6 (IL-6)
      secretion in cultured brainstem rat astrocytes. Ang II increased JAK2
      phosphorylation in a time- and dose-dependent manner. Maximal phosphorylation of
      1.7+/-0.4 fold above basal was observed at 15 min with 100 nM Ang II. Losartan
      (10 microM), an AT(1) receptor blocker, inhibited Ang II-mediated JAK2
      phosphorylation, while 10 microM PD123319, an AT(2) receptor blocker, was
      ineffective. The JAK2 inhibitor, AG490 (50 microM), prevented Ang II JAK2
      phosphorylation. Ang II also stimulated STAT3 in a concentration- and time
      dependent manner. Maximal phosphorylation of 0.8+/-0.11 above basal was observed
      at 15 min with 100 nM Ang II. Treatment with AG490 reduced Ang II phosphorylation
      of STAT3 and Ang II-induced astrocyte growth suggesting that JAK2 is an upstream
      signal in these Ang II effects. Ang II also stimulated IL-6 secretion from
      brainstem astrocytes in a concentration- and time-dependent manner. Maximal IL-6
      secretion of 0.7+/-0.2 above basal was observed with 100 nM Ang II after 48 h of
      treatment. Losartan decreased Ang II-induced IL-6 secretion while PD123319 was
      ineffective. Interestingly, AG490 reduced Ang II-stimulated IL-6 secretion. Our
      study showed for the first time that Ang II induced JAK2/STAT3 phosphorylation
      and IL-6 secretion through activation of the Ang II AT(1) receptor in brainstem
      astrocytes. In addition, Ang II stimulated IL-6 secretion and astrocyte growth
      through the JAK2 pathway in brainstem astrocytes. These results provide new
      insights into pro-inflammatory and mitogenic signaling mechanisms of Ang II in
      astrocytes.

PMID- 19748528
TI  - Induction of glioma apoptosis by microglia-secreted molecules: The role of nitric
      oxide and cathepsin B.
AB  - Microglia contributes significantly to brain tumor mass, particularly in
      astrocytic gliomas. Here, we examine the cytotoxic effects of soluble components
      secreted from microglia culture on glioma cells. Microglia conditioned culture
      medium (MCM) actively stimulated apoptotic death of glioma cells, and the effects
      of MCM prepared from LPS- or IFN-gamma-activated microglia were more pronounced.
      The cytotoxic effects were glioma-specific in that primary cultured rat
      astrocytes were not affected by MCM. A donor of peroxynitrite induced glioma
      specific cell death. In addition, NO synthase inhibitor suppressed glioma cell
      death induced by activated MCM, indicating that NO is one of the key molecules
      responsible for glioma cytotoxicity mediated by activated MCM. However, since
      unstimulated resting microglia produces low or very limited level of NO, MCM may
      contain other critical molecule(s) that induce glioma apoptosis. To identify the
      proteins secreted in MCM, proteomic analysis was performed on control or
      activated medium. Among over 200 protein spots detected by Coomassie blue
      staining, we identified 26 constitutive and 28 LPS- or IFN-gamma-regulated MCM
      proteins. Several cathepsin proteases were markedly expressed, which were reduced
      upon activation. In particular, suppression of cathepsin B by the chemical
      inhibitors significantly reversed MCM-induced glioma cell death, implying a
      critical role of this protease in cytotoxicity. Our findings provide evidence on
      the functional implications of specific microglial-secreted proteins in glioma
      cytotoxicity, as well as a basis to develop a proteomic databank of both basal
      and activation-related proteins in microglia.

PMID- 19748529
TI  - An auto-inducible Escherichia coli lysis system controlled by magnesium.
AB  - The Escherichia coli (E. coli) prokaryotic expression system is widely used in
      the field of biology. The currently adopted processes for inducing cell wall
      rupture, in order to release the target protein, are complex and cumbersome. We
      developed an auto-inducible E. coli lysis system that is regulated by exogenous
      magnesium ion (Mg(2+)) concentration. This system is composed of a strictly
      Mg(2+)-regulated promoter Pmgt from the mgtB gene of Salmonella typhimurium, and
      the lysis genes from lambda bacteriophage. Both the wild type and Sam7-mutant
      lysis genes were inducibly expressed in E. coli under Mg(2+)-depleted conditions.
      The former caused a rapid lysis, while the latter induced very mild lysis of the
      host strains. However, rapid lysis was observed when the latter was resuspended
      in Tris-EDTA buffer. Finally, the inducible lysis cassette containing wild type
      lysis gene was introduced into an expression plasmid expressing GFP gene and
      efficient lysis of the host E. coli strain and subsequent release of the target
      protein was achieved in Mg(2+)-depleted conditions. Collectively, the current
      study indicates that this novel inducible lysis system could have attractive
      applications in the field of protein expression and provides new insights for the
      development of bacterium-based vaccines.

PMID- 19748530
TI  - Quantitative cell wall protein profiling of invasive and non-invasive
      Saccharomyces cerevisiae strains.
AB  - A new, simple approach for the isolation and quantitative analysis of the cell
      wall (CW) proteins from invasively growing Saccharomyces cerevisiae strains is
      described in this contribution. The proposed method was proved compatible with
      agar-invasion assays and was demonstrated to be useful as a screening tool for
      rapid analysis of CW protein determinants related to yeast adhesion and invasion
      processes. CW protein isolation was performed enzymatically on viable cells by
      using mild, isosmotic reaction conditions and pure, proteinase free glucanase,
      thus avoiding destruction of cells and protein structures, which is a drawback of
      the existing methods based on hot SDS, DTT or NaOH treatment. Moreover, the
      method requires as low as 10mg of collected cell biomass for sufficient protein
      yield, which makes it suitable for the study of yeast invasion at the proteomic
      level. The extraction protocol was optimized for fast, direct analysis of
      multiple protein samples by SDS-PAGE, avoiding pre-concentration or purification
      steps, but still preserving high resolution of protein bands. The developed
      method was used to compare CW protein profile of i) invasive and non-invasive
      strains, ii) invasive and non-invasive morphological part of the colony and iii)
      cells cultivated at optimal and increased growth temperature. Results of
      quantitative SDS-PAGE analysis of S. cerevisiae CW proteins revealed the presence
      of up to 20 protein bands with molecular masses in the range 60-220 kDa. In
      addition, comparative analysis of CW protein profiles resulted in significant
      changes in the protein profile expression relevant to different cultivation
      temperature, cell morphology (invasive vs. non-invasive growth) and yeast strain.

PMID- 19748531
TI  - Utilizing RNA/DNA hybridization to directly quantify mRNA levels in microbial
      fermentation samples.
AB  - mRNA quantification has become a research hotspot. Quantitative real-time RT-PCR
      is a popular method but is known to lack precision. To rapidly monitor the
      kinetics of mRNA levels for the control of microbial fermentation processes, we
      developed an SYBR Green I-based universal method to directly quantify mRNA from
      fermentation samples. After total RNA was extracted, the mRNA was hybridized and
      protected by a longer DNA oligonucleotide. The probe length determined the
      strength of signal amplification. S1 nuclease and RNase A were used to remove
      excess probe, single-stranded RNA, and mis-matched RNA/DNA hybrids. Finally, the
      perfect-matched RNA/DNA hybrid was quantified by SYBR Green I dye. The conditions
      of liquid hybridization and enzyme digestion were systemically optimized. The
      kinetic tendency of phzC mRNA levels during phenazine-1-carboxylic acid
      fermentation was consistent with the results from MB hybridization in our
      previous report. The detection of mRNA levels of ten genes in Pseudomonas sp.
      M18G proved that this method is universal and feasible for mRNA quantification,
      and has great potential for application in mRNA quantification in various
      organisms.

PMID- 19748532
TI  - Stem-loop structure of Cocksfoot mottle virus RNA is indispensable for programmed
      -1 ribosomal frameshifting.
AB  - The -1 programmed ribosomal frameshifting (-1 PRF) mechanism utilized by many
      viruses is dependent on a heptanucleotide slippery sequence and a downstream
      secondary structure element. In the current study, the RNA structure downstream
      from the slippery site of cocksfoot mottle sobemovirus (CfMV) was proven to be a
      12bp stem-loop with a single bulge and a tetranucleotide loop. Several deletion
      and insertion mutants with altered stem-loop structures were tested in wheat germ
      extract (WGE) for frameshifting efficiency. The impact of the same mutations on
      virus infectivity was tested in oat plants. Mutations shortening or destabilizing
      the stem region reduced significantly but did not abolish -1 PRF in WGE. The same
      mutations proved to be deleterious for virus infection. However, extending the
      loop region to seven nucleotides had no significant effect on frameshifting
      efficiency in WGE and did not hamper virus replication in infected leaves. This
      is the first report about the experimentally proven RNA secondary structure
      directing -1 PRF of sobemoviruses.

PMID- 19748533
TI  - Complementation analysis of triple gene block of Potato virus S (PVS) revealed
      its capability to support systemic infection and aphid transmissibility of
      recombinant Potato virus X.
AB  - Triple gene block (TGB) sequences derived from isolates of ordinary Potato virus
      S (PVS-O) and Chenopodium-systemic (PVS-CS) were analyzed. Although the TGB
      sequences did not reveal any specific difference within the 7K protein, some
      specific differences within the 25K and 12K ORFs were found. In order to
      investigate a possible functional divergence of PVS-O and PVS-CS TGB variants,
      these genes were propagated in chimeric Potato virus X (PVX). Both PVS TGB
      variants partly complemented PVX TGB in Nicotiana benthamiana. The recombinant
      viruses multiplied to lower titer than the wild-type PVX in N. benthamiana showed
      attenuated symptoms. Whereas the recombinant PVX variants were also propagated
      systemically in Nicotiana glutinosa, Celosia argentea, Nicotiana occidentalis and
      chimeric PVX bearing TGB from PVS-O in Solanum lycopersicum, neither were
      propagated systemically in Chenopodium quinoa nor in Nicotiana tabacum cv. Samsun
      nn and the PVX-resistant Solanum tuberosum cv. Szignal. The potential for
      recombinant viruses to be transmitted by the aphid Myzus persicae was
      investigated. Aphid transmission in the recombinant virus was obtained by
      replacing PVX TGB by TGB from the PVS-CS isolate. These results show the
      potential function of Carlavirus TGB in aphid transmissibility and underlines the
      possible biological risks from certain recombinant virus variants.

PMID- 19748534
TI  - Detection of a novel porcine boca-like virus in the background of porcine
      circovirus type 2 induced postweaning multisystemic wasting syndrome.
AB  - Porcine circovirus type 2 (PCV-2) has been found to be the causative agent of
      postweaning multisystemic wasting syndrome (PMWS). However, PCV-2 is a ubiquitous
      virus in the swine population and a majority of pigs infected with PCV-2 do not
      develop the disease. Different factors such as age, maintenance, the genetics of
      PCV-2, other pathogens, etc. have been suggested to contribute to the development
      of PMWS. However, so far no proven connection between any of these factors and
      the disease development has been found. In this study we explored the possible
      presence of other so far unknown DNA containing infectious agents in lymph nodes
      collected from Swedish pigs with confirmed PMWS through random amplification and
      high-throughput sequencing. Although the vast majority of the amplified genetic
      sequences belonged to PCV-2, we also found genome sequences of Torque Teno virus
      (TTV) and of a novel parvovirus. The detection of TTV was expected since like PCV
      2, TTV has been found to have high prevalence in pigs around the world. We were
      able to amplify a longer region of the parvovirus genome, consisting of the
      entire NP1 and partial VP1/2. By comparative analysis of the nucleotide sequences
      and phylogenetic studies we propose that this is a novel porcine parvovirus, with
      genetic relationship to bocaviruses.

PMID- 19748535
TI  - Cellular signals involved in cyclooxygenase-2 expression induced by human
      cytomegalovirus.
AB  - Cyclooxygenase (COX)-2 plays an important role in inflammatory reaction and human
      cytomegalovirus (HCMV) is known to induce COX-2 gene expression. However, little
      is known for the mechanism of COX-2 gene expression by HCMV. In this study, three
      recently isolated HCMV strains including TB40/E and clinical isolates from Korean
      patients as well as highly laboratory adapted strain AD169 were used to stimulate
      COX-2 induction. Western blot analyses revealed that recently isolated HCMV
      strains induced COX-2 expression in human foreskin fibroblast (HFF) cells to
      higher levels than lab-adapted strain AD169. HCMV gene expression was not
      required for COX-2 induction since UV-inactivated virus was able to stimulate COX
      2 gene expression during immediate early infection. Moreover, when HCMV-infected
      HFF cells were transfected with small interfering RNA for major immediate early
      (MIE) genes, HCMV-induced COX-2 expression was not abrogated, suggesting that
      HCMV MIE genes are not needed for COX-2 expression. In order to understand the
      signal pathways involved in COX-2 gene expression induced by HCMV, selective
      inhibitors were used. When HCMV-infected HFF cells were treated with epidermal
      growth factor receptor (EGFR) kinase inhibitors and c-Raf/mitogen-activated
      protein kinases (MAPK, MEK) 1/2 inhibitors, HCMV-induced COX-2 expression was
      diminished. However, COX-2 expression by HCMV infection was not inhibited if HCMV
      infected HFF cells were treated with inhibitors of phosphatidylinositol-3-kinase,
      c-Jun N-terminal kinase, nuclear factor kappa B, p-38 MAPK and Rho-associated
      protein kinase. We concluded that EGFRK, Raf, MEK1/2 and extracellular signal
      regulated kinases (ERK 1/2) pathway may participate in the COX-2 mediated
      inflammatory response to HCMV infection.

PMID- 19748536
TI  - Enhanced in vivo bioluminescence imaging using liposomal luciferin delivery
      system.
AB  - To provide a continuous and prolonged delivery of the substrate D-luciferin for
      bioluminescence imaging in vivo, luciferin was encapsulated into liposomes using
      either the pH gradient or acetate gradient method. Under optimum loading
      conditions, 0.17 mg luciferin was loaded per mg of lipid with 90-95%
      encapsulation efficiency, where active loading was 6 to 18-fold higher than that
      obtained with passive loading. Liposomal luciferin in a long-circulating
      formulation had good shelf stability, with 10% release over 3-month storage at 4
      degrees C. Pharmacokinetic profiles of free and liposomal luciferin were then
      evaluated in transgenic mice expressing luciferase. In contrast to rapid in vivo
      clearance of free luciferin (t(1/2)=3.54 min), luciferin encapsulated into long
      circulating liposomes showed a prolonged release over 24h. The first-order
      release rate constant of luciferin from long-circulating liposomes, as estimated
      from the best fit of the analytical model to the experimental data, was 0.01 h(
      1). Insonation of luciferin-loaded temperature-sensitive liposomes directly
      injected into one tumor of Met1-luc tumor-bearing mice resulted in immediate
      emission of light. Systemic injection of luciferin-loaded long-circulating
      liposomes into Met1-luc tumor-bearing mice, followed by unilateral ultrasound
      induced hyperthermia, produced a gradual increase in radiance over time, reaching
      a peak at 4-7 h post-ultrasound.

PMID- 19748537
TI  - Immune response to controlled release of immunomodulating peptides in a murine
      experimental autoimmune encephalomyelitis (EAE) model.
AB  - The effects of controlled release on immune response to an immunomodulating
      peptide were evaluated in a murine experimental autoimmune encephalomyelitis
      (EAE) model of multiple sclerosis (MS). The peptide, Ac-PLP-BPI-NH(2)-2 (Ac
      HSLGKWLGHPDKF-(AcpGAcpGAcp)(2)-ITDGEATDSG-NH(2); Ac = acetyl, Acp = epsilon
      aminocaproic acid) was designed to suppress T-cell activation in response to
      PLP(139-151), an antigenic peptide in MS. Poly-lactide-co-glycolide (PLGA)
      microparticles containing Ac-PLP-BPI-NH(2)-2 (8+/-4 microm, 1.4+/-0.2% (w/w))
      were prepared by a powder-in oil-in water emulsion-solvent evaporation method,
      sterilized and administered subcutaneously (s.c.) to SJL/J (H-2(s)) mice in which
      EAE had been induced by immunization with PLP(139-151). Treatment groups received
      Ac-PLP-BPI-NH(2)-2: (i) in solution by repeated i.v. or s.c. injection, (ii) in
      solution co-administered with blank PLGA microparticles, (iii) in solution co
      administered with Ac-PLP-BPI-NH(2)-2 loaded microparticles, and (iv) as Ac-PLP
      BPI-NH(2)-2 loaded microparticles. Administration of Ac-PLP-BPI-NH(2)-2 as an
      s.c. solution produced clinical scores and maintenance of body weight comparable
      to i.v. solution, but with reduced overall survival, presumably due to
      anaphylaxis. Administration as s.c. microparticles provided a somewhat less
      effective reduction in symptoms but with no toxicity during treatment. Thus, the
      results suggest that s.c. administration of Ac-PLP-BPI-NH(2)-2 microparticles can
      provide pharmacological efficacy and reduction in dosing frequency without
      increased toxicity.

PMID- 19748538
TI  - Feeding association between the nucleus of the solitary tract and the ventral
      tegmental area.
AB  - Male Sprague-Dawley rats were fitted with two cannulae in the VTA and one cannula
      in the NTS for co-administration of the micro-opioid receptor agonist DAMGO in
      one site and the opioid antagonist naltrexone in the other. Injection of DAMGO
      into the VTA or the NTS stimulated feeding. The increase in food intake after
      DAMGO injection into the VTA was decreased following injection of naltrexone into
      the NTS. Furthermore, the increase in food intake after DAMGO injection into the
      NTS was decreased following injection of naltrexone into the VTA. These results
      suggest an opioid-mediated feeding association between the VTA and NTS.

PMID- 19748539
TI  - HLA class I molecules reflect an altered host proteome after influenza virus
      infection.
AB  - Class I HLA sample and display peptides from thousands of endogenous proteins at
      the cell surface. During infection, the influenza virus modifies the host cell
      proteome by triggering host antiviral responses, hijacking host processes, and
      inhibiting host mRNA processing. In turn, the catalog of HLA class I peptides
      that decorate the surface of an infected cell is positioned to reflect an altered
      host cell proteome. To understand the host-encoded peptides presented by class I
      molecules after influenza infection, we compared by mass spectrometry (MS) the
      peptides eluted from the HLA of naive and infected cells. We identified 20
      peptide ligands unique to infected cells and 347 peptides with increased
      presentation after infection. Infection with different influenza strains
      demonstrated that proteome changes are predominantly strain-specific, with few
      individual cellular interactions observed for multiple viral strains. Modeling by
      pathway analysis, however, revealed that strain specific host peptide changes
      represent different routes to the same destination; host changes mediated by
      influenza are found predominantly clustered around HLA-B, ACTB, HSP90AB1, CDK2,
      and ANXA2. The class I HLA proteome scanning of influenza-infected cells
      therefore indicates how divergent strains of influenza pursue alternate routes to
      access the same host cell processes.

PMID- 19748540
TI  - Neural correlates of impaired emotional discrimination in borderline personality
      disorder: an fMRI study.
AB  - A common approach to study neuronal aspects of emotional reactivity of borderline
      personality disorder (BPD) is to study the brain response to emotional faces with
      functional magnetic resonance imaging (fMRI). 10 BPD patients and 10 matched
      controls were submitted to an emotional discrimination task in which subjects had
      to identify an emotional face from a neutral face while fMRI data was acquired.
      BPD patients made more mistakes than controls in the discrimination task when
      negative faces were involved. The emotional discrimination task activated brain
      areas that are known to participate in processing of emotional faces (fusiform
      gyrus, insula and amygdala) regardless of the psychiatric condition.
      Additionally, BPD showed higher activation than controls in the middle and
      inferior temporal cortical areas, brain areas that participate in the processing
      of face features that carry emotional value. Furthermore, activity at this site
      correlated with impulsivity score in the Zuckerman-Kuhlman Personality
      Questionnaire. Our findings may be related to cognitive impairment that may be
      characteristic of the disorder.

PMID- 19748541
TI  - Anterior cingulate cortex activation as a trait of panic disorder in a patient
      with a temporal arachnoid cyst.

PMID- 19748542
TI  - TPH2 is not a susceptibility gene for suicide in Japanese population.
AB  - BACKGROUND: Serotonergic systems mediate a control of aggression and/or
      impulsivity in human and are suggested to be involved in suicidal behavior. The
      newly identified neuronal tryptophan hydroxylase isoform 2 (TPH2), the rate
      limiting enzyme in serotonin synthesis, represents a prime candidate in numerous
      genetic association analyses of suicidal behavior; however, the results are still
      inconclusive. The discrepancy may result from the heterogeneity of pathogenesis
      of suicidal behavior and/or methodological mismatches. We, therefore, attempted
      to replicate the association of TPH2 gene with suicide using a case-control study
      of 234 completed suicides and 260 control subjects in Japanese population.
      METHODS: We genotyped 15 tagging-single nucleotide polymorphisms (SNPs) including
      4 SNPs, which were previously reported to be associated with suicidal behavior,
      using the TaqMan probe assays and the polymerase chain reaction and restriction
      fragment length polymorphism (PCR-RFLP) method. RESULTS: We found no significant
      differences in genotypic distributions (uncorrected p=0.06-0.98) or allelic
      frequencies (uncorrected p=0.09-0.95) of the fifteen SNPs between the completed
      suicides and control groups. Haplotypes constructed with these SNPs were also not
      associated with suicide (uncorrected p=0.03-0.96 and corrected p=0.20-1.00). Even
      when we took sex and suicidal methods (violent or non-violent) into account for
      the analyses, no significant differences in genotypic distributions,
      allelic/haplotypic frequencies were found in the two groups. CONCLUSION: Our
      results suggest that the common SNPs and haplotypes of the TPH2 gene are unlikely
      to contribute to the genetic susceptibility to suicidal behavior in Japanese
      population.

PMID- 19748543
TI  - Antioxidant properties of raspberry seed extracts on micronucleus distribution in
      peripheral blood lymphocytes.
AB  - This study addresses in vitro effects of raspberry (Rubus idaeus) seed extracts
      (RSE) on the frequency of micronuclei. We evaluated the effects of three
      different extracts (50%, 80%, and 100% methanol) in doses of 1.4, 4.2, and 8.4
      microg/mL, per 5 mL culture using cytochalasin-B micronucleus (CBMN) assay in
      peripheral human lymphocytes. The frequency of MN was scored in binucleated (BN)
      cells. The nuclear proliferation index was also calculated. The distribution of
      polyphenolic compounds in RSEs was determined using LC/UV/ESI-TOF MS. The
      identified 37 compounds comprised flavanol monomers and oligomers, as well as
      varieties of ellagitannin components. Treatment of lymphocytes with RSEs induced
      a significant decrease in the frequency of micronuclei by 80%. These results
      demonstrate that the constituents of RSEs may be important in the prevention of
      oxidative lymphocyte damage by reactive oxygen species and may also reduce the
      level of DNA damage. These findings support the potential benefits of
      polyphenolic compounds from raspberry seeds as efficient antioxidants.

PMID- 19748544
TI  - Protective role of carnosine in mice with cadmium-induced acute hepatotoxicity.
AB  - The hepatoprotective effect of carnosine was investigated against cadmium-induced
      acute liver injury in mice. Hepatotoxicity was induced by a single i.p. injection
      of cadmium chloride (6.5mg/kg). Carnosine treatment (10mg/kg/day, i.p.) was
      applied for three consecutive days, starting one day before cadmium
      administration. Carnosine significantly decreased the cadmium-induced elevations
      in serum aminotransferases. Carnosine suppressed lipid peroxidation and restored
      the deficits in the antioxidant defense mechanisms (reduced glutathione level,
      and catalase and superoxide dismutase activities) in liver tissue resulted from
      cadmium administration. Also, the reductions in hepatic nitric oxide and zinc ion
      levels, and the increases in hepatic cadmium ion concentration, and
      myeloperoxidase and caspase-3 activities following cadmium exposure were
      significantly attenuated by carnosine treatment. In addition, carnosine markedly
      ameliorated cadmium-induced liver tissue damage as evidenced by light and
      electron microscopic examinations. It was concluded that carnosine can be
      considered a potential candidate to protect the liver against the deleterious
      effect of acute cadmium intoxication.

PMID- 19748545
TI  - Chemical composition and antioxidant activities of the essential oil and methanol
      extracts of Psammogeton canescens.
AB  - This study is outlined to probe the chemical composition of essential oil and in
      vitro antioxidant activity of the essential oil and methanol extracts of
      Psammogeton canescens. The chemical composition of the hydrodistilled essential
      oil of the aerial parts of P. canescens was analyzed by GC and GC/MS. The main
      constituents of the oil were found to be beta-bisabolene (33.35%), apiole
      (28.34%), alpha-pinene (11.86%) and dill apiole (8.17%). Antioxidant activities
      of the samples were determined by three various testing systems namely DPPH, beta
      carotene/linoleic acid, and reducing power assay. In DPPH system, the highest
      radical-scavenging activity was seen by the polar subfraction of methanol extract
      (49.5+/-1.21mug/ml). Furthermore, in the second case the inhibition capacity (%)
      of the polar subfraction (92.40%+/-0.72) found to be the stronger one. However,
      in the reducing power assay, a reverse activity pattern more than in the first
      two systems was observed, and the essential oil was stronger radical reducer than
      was the methanol extract in all of the concentration tested. Our findings
      demonstrate that the essential oil and methanol extracts of P. canescens possess
      significant antioxidant activities and may be suggested as a new potential source
      of natural antioxidant.

PMID- 19748546
TI  - Genotoxic evaluation of sodium fluoride in the Somatic Mutation and Recombination
      Test (SMART).
AB  - In this study, genotoxic effect of sodium fluoride (NaF) was investigated in
      Drosophila melanogaster Somatic Mutation and Recombination Test. Third-instar
      larvae trans-heterozygous for two genetic markers mwh and flr, were treated at
      different concentrations (2.5 microg/ml, 5 microg/ml and 10 microg/ml) of the
      test compounds. After the treatment the observed mutations were classified
      according to size and type of mutation per wing. For the evaluation of genotoxic
      effects, the frequencies of spots per wing in the treated series were compared to
      the control group, which is distilled water. NaF has genotoxic and toxic effects
      for concentrations of 5 and 10 microg/ml. The present study shows that NaF may
      have genotoxic and toxic effects.

PMID- 19748547
TI  - Correlations and co-localizations of Hsp70 with XPA, XPG in human bronchial
      epithelia cells exposed to benzo[a]pyrene.
AB  - Benzo[a]pyrene (BaP) is a ubiquitously distributed environmental pollutant known
      to cause DNA damage, which may be repaired through nucleotide excision repair
      (NER). The significantly negative correlation between Hsp70 levels and the level
      of DNA damage in workers exposed to coke oven emission had been found. However,
      little is known about how Hsp70 modulate the DNA repair process. In a series of
      experiments using the human bronchial epithelia cells (16HBE) exposed to
      different concentrations of BaP for 24h, we measured expression of NER subunit
      xeroderma pigmentosum (XP) group A, C, F, G (XPA, XPC, XPF, XPG), excision repair
      cross-complementing 1 (ERCC1) and Hsp70, and analyzed their possible
      correlations. Co-localizations of Hsp70 with NER subunit were detected by
      confocal microscope. We found that in vitro exposure to BaP reduced cell
      viability in a dose-dependent manner ranging from 2 to 64 microM. Our results
      showed that levels of XPA, XPG and Hsp70 significantly increased at cells exposed
      to 1 or 2muM BaP. In addition, curve estimation showed there was a significant
      correlation between relative ratios of Hsp70 and XPA, XPG in cells exposed to
      different concentrations of BaP. Moreover, confocal microscopy demonstrated
      increased co-localization of Hsp70 with XPA, XPG in nuclei of cells exposed to
      BaP. These results suggested that Hsp70 might play a role in nucleotide excision
      repair. However, the mechanisms underlying this observation need further
      investigation.

PMID- 19748548
TI  - Clinical and SEM assessment of ART high-viscosity glass-ionomer sealants after 8
      13 years in 4 teeth.
AB  - OBJECTIVES: Resin composite sealants are retained longer than low-viscosity glass
      ionomer sealants. Nevertheless, a systematic review showed that there is no
      evidence that resin composite sealants are superior to low-viscosity glass
      ionomers in preventing dentine carious lesion development. This case study aimed
      to investigate reasons for this. METHODS: 4 teeth were sealed with 2 brands of
      high-viscosity glass-ionomer according to the ART technique in 2 children aged 10
      and 11.5 years, having a low caries-risk status, and followed clinically for
      between 8 and 13 years. At the final year, impressions were taken for SEM images
      that were assessed by two evaluators. RESULTS: Pits and fissures that were
      clinically diagnosed as free of sealant material appeared to contain remnants of
      high-viscosity glass-ionomer sealant material in the deeper parts of pits and
      fissures, on SEM images of 3 teeth. CONCLUSION: This study confirms the
      likelihood that remnants of high-viscosity glass-ionomer sealant material are
      retained and block the deeper parts of pits and fissures even after the sealant
      appears to have disappeared clinically, exercising their carious lesion
      preventive effect.

PMID- 19748549
TI  - Accelerated cellular senescence in myelodysplastic syndrome.
AB  - OBJECTIVE: To investigate the contribution of cellular senescence to the
      progression and prognosis of myelodysplastic syndrome (MDS). MATERIALS AND
      METHODS: We have analyzed the expression of p16INK4a in bone marrow mononuclear
      cells or CD34(+) cells from 53 patients with MDS, 12 acute myeloid leukemia
      (AML), and 11 healthy controls. Additionally, We have assessed quantitatively
      senescence-associated beta-galactosidase (SA-beta-gal) staining on bone marrow
      mononuclear cells from MDS and AML patients, HL60 and SHI-1 leukemia cell lines,
      and healthy control cells. RESULTS: An upregulated expression of senescence
      associated molecular marker p16INK4a was found in MDS compared with healthy
      controls, while a lower expression of p16INK4a was observed in AML compared with
      healthy controls. International Prognostic Scoring System score was negatively
      correlated with the percentage of p16INK4a-positive cells. The SA-beta-gal
      activity measured by mean percentage of positive cells was significantly higher
      in MDS cases when compared with controls. Meanwhile, percentage of SA-beta-gal
      positive cells was also remarkably higher in dysplastic cells of MDS when
      compared to nondysplastic cells from MDS. CONCLUSIONS: These results of our
      present study suggested an accelerated cellular senescence occurred in MDS, and
      the cellular senescence may be involved in the progression and prognosis of MDS.

PMID- 19748550
TI  - Structural analyses of sex hormone-binding globulin reveal novel ligands and
      function.
AB  - Plasma sex hormone-binding globulin (SHBG) regulates the access of androgens and
      estrogens to their target tissues and cell types. An SHBG homologue, known as the
      androgen-binding protein, is expressed in Sertoli cells of many mammalians, but
      testicular expression of human SHBG is restricted to germ cells. The primary
      structure of SHBG comprises tandem laminin G-like (LG) domains. The amino
      terminal LG-domain includes the steroid-binding site and dimerization interface,
      and its tertiary structure, resolved in complex with natural and synthetic sex
      steroids, has revealed unanticipated mechanisms of steroid binding at the atomic
      level. This LG-domain interacts with fibulin-1D and fibulin-2 in a ligand
      specific manner, and this is attributed to the unique way estrogens reside within
      the steroid-binding site, and the ordering of an otherwise flexible loop
      structure covering the entrance of the steroid-binding pocket. This mechanism
      enables estradiol to enhance the sequestration of plasma SHBG by the stroma of
      some tissues through binding to these extra-cellular matrix-associated proteins.
      The human SHBG amino-terminal LG-domain also contains several cation-binding
      sites, and occupancy of a zinc-binding site influences its affinity for
      estradiol. The complete quaternary structure of SHBG remains unresolved but
      structural predictions suggest that the carboxy-terminal LG-domains extend
      laterally from the dimerized amino-terminal LG-domains. The carboxy-terminal LG
      domain contains two N-glycosylation sites, but their biological significance
      remains obscure. Knowledge of the SHBG tertiary structure has helped develop
      computational techniques based on the use of a "bench-mark data set" of steroid
      ligands, and created novel drug discovery and toxicology risk assessment
      platforms.

PMID- 19748551
TI  - Fractalkine/CX3CL1 enhances GABA synaptic activity at serotonin neurons in the
      rat dorsal raphe nucleus.
AB  - Serotonin (5-hydroxytryptamine; 5-HT) has an important role in mood regulation,
      and its dysfunction in the central nervous system (CNS) is associated with
      depression. Reports of mood and immune disorder co-morbidities indicate that
      immune-5-HT interactions may mediate depression present in immune compromised
      disease states including HIV/AIDS, multiple sclerosis, and Parkinson's disease.
      Chemokines, immune proteins that induce chemotaxis and cellular adhesion, and
      their G-protein coupled receptors distribute throughout the CNS, regulate
      neuronal patterning, and mediate neuropathology. The purpose of this study is to
      investigate the neuroanatomical and neurophysiological relationship between the
      chemokine fractalkine/CX3CL1 and its receptor CX3CR1 with 5-HT neurons in the rat
      midbrain raphe nuclei (RN). Immunohistochemistry was used to examine the
      colocalization of CX3CL1 or CX3CR1 with 5-HT in the RN, and whole-cell patch
      clamp recordings in rat brain slices were used to determine the functional impact
      of CX3CL1 on 5-HT dorsal raphe nucleus (DRN) neurons. Greater than 70% of 5-HT
      neurons colocalize with CX3CL1 and CX3CR1 in the RN. CX3CL1 localizes as discrete
      puncta throughout the cytoplasm, whereas CX3CR1 concentrates to the perinuclear
      region of 5-HT neurons and exhibits microglial expression. CX3CL1 and CX3CR1 also
      colocalize with one another on individual RN cells. Electrophysiology studies
      indicate a CX3CL1-mediated enhancement of spontaneous inhibitory postsynaptic
      current (sIPSC) amplitude and dose-dependent increase of evoked IPSC (eIPSC)
      amplitude without affecting eIPSC paired-pulse ratio, a finding observed
      selectively in 5-HT neurons. CX3CL1's effect on eIPSC amplitude is blocked by
      pretreatment with an anti-CX3CL1 neutralizing antibody. Thus, CX3CL1 enhances
      postsynaptic GABA receptor number or sensitivity on 5-HT DRN neurons under
      conditions of both spontaneous and synaptically-evoked GABA release. CX3CL1 may
      indirectly inhibit 5-HT neurotransmission by increasing the sensitivity of 5-HT
      DRN neurons to GABA inputs. Therapies targeting CX3CL1 may treat serotonin
      related mood disorders, including depression experienced by patients with
      compromised immune systems.

PMID- 19748552
TI  - Valproic acid as a promising agent to combat Alzheimer's disease.
AB  - Alzheimer's disease (AD) is one of the most threatening diseases to the elderly
      population at present. However, there is no yet efficient therapeutic method to
      AD. Recently, accumulating evidence indicates that valproic acid (VPA), a widely
      used mood stabilizer and antiepileptic drug, has neuroprotective potential
      relevant to AD. Moreover, VPA can induce neurogenesis of neural progenitor/stem
      cells both in vitro and in vivo via multiple signaling pathways. Therefore, it is
      suggested that VPA is a promising agent to combat AD.

PMID- 19748553
TI  - Effects of olanzapine, fluoxetine and olanzapine/fluoxetine on creatine kinase
      activity in rat brain.
AB  - Recently, a fixed combination of the atypical antipsychotic olanzapine and the
      serotonin selective reuptake inhibitor (SSRI) fluoxetine has been approved in the
      US for the treatment of bipolar I depression. In this work, we evaluated the
      effect of acute and chronic administration of fluoxetine, olanzapine and the
      combination of fluoxetine/olanzapine on creatine kinase (CK) activity in the
      brain of rats. For acute treatment, adult male Wistar rats received one single
      injection of olanzapine (3 or 6 mg/kg) and/or fluoxetine (12.5 or 25mg/kg). For
      chronic treatment, adult male Wistar rats received daily injections of olanzapine
      (3 or 6 mg/kg) and/or fluoxetine (12.5 or 25mg/kg) for 28 days. In the present
      study we observed that acute administration of OLZ inhibited CK activity in
      cerebellum and prefrontal cortex. The acute administration of FLX inhibited
      creatine kinase in cerebellum, prefrontal cortex, hippocampus, striatum and
      cerebral cortex. In the chronic treatment, when the animals were killed 2h after
      the last injection a decrease in creatine kinase activity after FLX
      administration, alone or in combination with OLZ, in cerebellum, prefrontal
      cortex, hippocampus, striatum and cerebral cortex of rats occurred. However, when
      the animals were killed 24h after the last injection, we found no alterations in
      the enzyme. Although it is difficult to extrapolate our findings to the human
      condition, the inhibition of creatine kinase activity by these drugs may be
      associated to the occurrence of some side effects of OLZ and FLX.

PMID- 19748554
TI  - Antioxidant flavonoid glycosides from Evolvulus alsinoides.
AB  - Oxidative damage is an established outcome of chronic stress. Thus, the present
      study was designed to investigate the modulatory role of ethanolic extract of
      Evolvulus alsinoides (EA) in terms of oxidative alterations at peripheral and
      central level in rats subjected to chronic unpredictable stress (CUS). CUS
      exposure for 7 days reduced Cu, Zn superoxide dismutase and catalase activity
      with increase in glutathione peroxidase activity and lipid peroxidation, while
      decrease in reduced glutathione level in blood plasma, frontal cortex and
      hippocampus regions of brain. Oral administration of EA extract at 200mg/kg p.o.
      normalized these stress induced oxidative alterations with an efficacy similar to
      that of melatonin. Further, EA extract was taken up for detailed chemical
      investigation. Two new flavonol-4'-glycoside, kaempferol 4'-O-beta-D
      glucopyranosyl-(1-->2)-beta-D-glucopyranoside (3) and kaempferol 4'-O-alpha-L
      rhamnopyranosyl-(1-->6)-beta-D-glucopyranoside (5) were isolated, along with
      eight known compounds (1, 2, 4 and 6-10). The structures of new compounds were
      established by detailed spectroscopic studies, while known compounds were
      characterized by direct comparison of their reported NMR data. All these
      compounds were evaluated for their in vitro antioxidant activity. Compounds 3, 5,
      9 and 10 at 100 and 200 microg/ml showed significant in vitro antioxidant
      activity. Therefore, EA may hold great potential in preventing clinical
      deterioration in stress induced oxidative load and related disorders.

PMID- 19748555
TI  - Reward type influences performance and search structure of an omnivorous bird in
      an open-field maze.
AB  - Open-field mazes are routinely used to study the spatial cognitive abilities of
      birds and are often implicitly assumed to be suitable tests of generic spatial
      memory ability. In recent years there has been extensive research motivated by
      considerations of an animals' ecology, demonstrating potential examples of
      specialisations of spatial cognition, as a result of foraging niche. The study
      reported here demonstrates differences in maze performance as a function of
      reward type (nectar and invertebrates) that can be predicted from the natural
      distributions of these rewards. As well as specific implications for the nature
      of spatial memory specialisation in this species, the results hold more general
      implications for the use of open-field mazes as tools for measuring and comparing
      spatial memory ability between species.

PMID- 19748556
TI  - Methylmercury elicits intracellular Zn2+ release in rat thymocytes: its relation
      to methylmercury-induced decrease in cellular thiol content.
AB  - We have previously revealed that thimerosal, an organomercurial preservative,
      increases intracellular Zn(2+) concentration in rat thymocytes. Because
      thimerosal contains ethylmercury that confers the toxicity, it is a possibility
      that methylmercury (MetHg), an environmental pollutant, also increases
      intracellular Zn(2+) concentration. This possibility was tested by measuring
      intracellular Zn(2+) level with FluoZin-3, a fluorescent probe for intracellular
      Zn(2+). MetHg at concentrations ranging from 100 nM to 1 microM significantly
      increased the intensity of FluoZin-3 fluorescence, an indicator for intracellular
      Zn(2+) concentration, under external Ca(2+)- and Zn(2+)-free condition in a
      concentration-dependent manner. TPEN, a chelator for intracellular Zn(2+),
      completely diminished the MetHg-induced augmentation of FluoZin-3 fluorescence.
      MetHg at 100 nM or more significantly decreased the intensity of 5
      chlormethylfluorescein fluorescence, an indicator for cellular thiol content.
      Such MetHg-induced changes in the fluorescence were correlated with a coefficient
      of -0.917. Taken together, it is suggested that submicromolar MetHg releases
      Zn(2+) from intracellular thiol, resulting in the increase in intracellular
      Zn(2+) concentration. However, it is unlikely that MetHg at critical maternal
      blood concentration (27 nM) affects intracellular Zn(2+) homeostasis.

PMID- 19748557
TI  - Effects of extrusion process parameters on the dissolution behavior of
      indomethacin in Eudragit E PO solid dispersions.
AB  - This work studied the dissolution of indomethacin (INM) into polymer excipient
      Eudragit E PO (E PO) melt at temperatures lower than the melting point of INM
      using a laboratory-size, twin-screw counter-rotating batch internal mixer. The
      effects of three process parameters--set mixer temperature, screw rotating speed
      and residence time--were systematically studied. Scanning electron microscopy
      (SEM), optical microscopy (OM), X-ray diffraction (XRD) and Fourier transform
      infrared spectroscopy (FT-IR) were employed to investigate the evolution of INM's
      dissolution into the molten excipient. Differential scanning calorimetry (DSC)
      was used to quantitatively study the melting enthalpy evolution of the drug. The
      results showed that the dissolution rate increased with increasing the mixer set
      temperature, or the screw rotating speed. It was concluded that the dissolution
      of the drug in the polymer melt is a convective diffusion process, and that
      laminar distributive mixing can significantly enhance the dissolution rate. More
      importantly, the time needed for the drug to dissolve inside the molten polymer
      and the typical residence time for an extrusion process fall in the same range.

PMID- 19748558
TI  - Drug release from PLGA-based microparticles: effects of the "microparticle:bulk
      fluid" ratio.
AB  - The aim of this study was to better understand the importance of the
      "microparticle mass:bulk fluid volume" ratio during in vitro drug release
      measurements from PLGA microparticles. Initially porous/non-porous,
      ibuprofen/lidocaine/propranolol HCl-loaded systems were exposed to phosphate
      buffer pH 7.4 in agitated test tubes, varying the microparticle concentration
      from 5:1 to 20:1mg:mL. Interestingly, drug release was virtually unaffected by
      the "microparticle mass:bulk fluid volume" ratio in the case of initially porous,
      ibuprofen-loaded microparticles, exhibiting complete drug release within about 1
      week. Optical microscopy, SEM, DSC and pH measurements of the bulk fluid revealed
      no major impact of the microparticle concentration on the systems' properties
      within the first couple of days. However, a more rapid and pronounced decrease in
      the pH of the release medium occurred after 10-14 d at elevated "microparticle
      mass:bulk fluid volume" ratios. This resulted in an accelerated: (i) decrease in
      the glass transition temperature, (ii) microparticle agglomeration, and (iii)
      increase in the internal and external microparticle porosity. Importantly, this
      phenomenon did not significantly affect drug release from initially porous,
      lidocaine-loaded microparticles, exhibiting complete release within about 18 d.
      In contrast, drug release became significantly faster at higher "microparticle
      mass:bulk fluid volume" ratios in the case of initially non-porous, lidocaine
      loaded microparticles and initially porous, propranolol HCl-loaded systems,
      exhibiting complete release after 1 and 2 months, respectively. Thus, depending
      on the type of system, the "microparticle mass:bulk fluid volume" ratio may or
      may not affect the observed release kinetics in vitro. This should be carefully
      taken into account when defining the experimental conditions for drug release
      measurements from this type of advanced drug delivery systems.

PMID- 19748559
TI  - A new bioerodible system for sustained local drug delivery based on
      hydrolytically activated in situ macromolecular association.
AB  - To prolong the duration of polymer erosion over existing approaches for sustained
      local drug delivery, we investigated a new bioerodible system based on
      hydrolytically activated in situ formation of interpolymer complexes in binary
      blends of high MW poly(vinyl methyl ether-co-maleic anhydride) (PVMMA) and
      poly(ethylene oxide) (PEO). In an aqueous environment of use, the hydrophobic
      PVMMA component of the blend undergoes hydrolysis converting the anhydride to
      free carboxylic acid groups which in turn form in situ intermolecular complexes
      with the PEO component of the blend. The formation of such hydrogen-bonded
      complexes with a condensed structure at the blend surface helps to retard the
      further progression of polymer erosion and drug release. The effects of PVMMA/PEO
      composition on blend morphology, polymer erosion and drug release were evaluated
      with the aid of fluorescence labeled PVMMA. The results show a decrease in
      miscibility in PVMMA/PEO blend with increasing PEO content. At low PEO contents
      (below 40%), the in vitro rate of release of a model drug metronidazole decreases
      with increasing PEO content, resulting in extended release duration over several
      days. On the other hand, excessive phase separation at PEO contents above 40%
      gives rise to higher rate and shorter duration of drug release.

PMID- 19748560
TI  - Optimization of PLG microspheres for tailored drug release.
AB  - Here we explore the opportunity to design and then produce tailored release of
      therapeutic drugs from microcapsules. By use of "building blocks," formed from
      well characterized microcapsule populations, an inverse design algorithm has been
      developed that provides an optimal (in a least squares sense) combination of
      building blocks to achieve a desired release history. Previously we have reported
      experiments and a well validated mathematical model for computing drug release
      histories from PLG microcapsules, and these form the backbone of the present
      optimization algorithm. To expand our available basis for finding useful optimal
      solutions, we also report work to validate the mathematical model for two
      different molecular weights. Thus, our building blocks comprise populations that
      differ by microsphere mean diameter, polydispersity, and polymer molecular
      weight, giving three separate parameters that effect drug release rate, and from
      which we build a foundation for our tailored release. Here we have taken a basis
      of six different microcapsule release systems, from which we build a tailored
      release history using constrained optimization to fit a prescribed release
      profile. Comparison of predicted release with measurements from the tailored
      microcapsule populations was found to produce excellent results, with correlation
      coefficients greater than 0.98. By way of demonstration, a triple pulse design is
      described that illustrates the power of the method.

PMID- 19748561
TI  - Magnesium stearate increases salbutamol sulphate dispersion: what is the
      mechanism?
AB  - The objective was to understand the mechanism of enhancement in salbutamol
      sulphate (SS) respiratory deposition through addition of magnesium stearate
      (MgSt). The mixing of MgSt with micronized SS occurred using a Turbula mixer (101
      rpm), whilst varying mixing time and MgSt concentration and size. Deposition of
      SS was determined by a twin-stage impinger. Particle size distributions were
      obtained using the Malvern Mastersizer 2000. Morphology was examined by scanning
      electron microscopy and surface energy determined using inverse gas
      chromatography. Mixing of SS with increasing concentrations of MgSt improved
      dispersion (FPF of 3.3% using 1% w/w MgSt, 4.5% using 5% w/w MgSt and 7.8% using
      10% w/w MgSt compared with 1.4% of pure SS for 20mg doses) when mixed for 0.5h;
      SS dispersion improved further after 3.5h of mixing. In addition to the action of
      the MgSt in coating SS particles, a greater understanding of the function of MgSt
      particles in acting as micro-carriers and in changing the mixture structure
      through incorporation into agglomerates has been achieved. The mechanistic
      understanding of improvement in drug deposition using MgSt will allow more
      directed strategies to be employed in designing powder formulations for
      inhalation.

PMID- 19748562
TI  - In vitro assessment of liposomal neridronate on MDA-MB-231 human breast cancer
      cells.
AB  - Bisphosphonates have been used for decades in the standard therapy of bone
      related diseases, including bone metastasis of various malignancies, and they
      might as well be toxic on early cancer cells themselves. In order to allow a
      better delivery of neridronate (a N-containing bisphosphonate with relatively
      poor activity), liposomes were evaluated in vitro on cancer cell lines (MDA-MB
      231, U87-MG and Caco2). After chemical synthesis, this water-soluble molecule was
      encapsulated into liposomes containing DOPC:DOPG:Chol (72:27:1 molar ratio). The
      influence of neridronate (free or liposomal) on cell viability or proliferation
      after treatment was evaluated using the MTT method, as well as cell migration and
      invasion assays; these techniques showed a drastic improvement of the action of
      neridronate on MDA-MB-231 cells with an EC(50) 50 times lower when neridronate
      was encapsulated. Internalization of liposomes was followed by flow cytometry and
      fluorescence microscopy, demonstrating internalization via the endocytic pathway.
      Furthermore, since overexpression of matrix metalloproteinases (particularly MMP
      2 and MMP-9) has been correlated to poor prognosis in many cancer types,
      detection of MMP expression is a satisfactory indication of the therapy
      efficiency and was then performed on treated cells. On MDA-MB-231 cells, MPPs
      expression was also significantly reduced by neridronate while entrapped in
      liposomes.

PMID- 19748563
TI  - Study of gel-forming properties of sucrose esters for thermosensitive drug
      delivery systems.
AB  - Sucrose esters (SEs) are non-toxic, biodegradable, non-ionic surfactants. They
      have a wide range of hydrophilic-lipophilic balance values (1-16) and are usually
      applied as surfactants, or as solubility or penetration enhancers. The aims of
      this work were to study the gelling behaviour of SEs and the effects of this
      property on drug release. The gelling characteristics of two different SEs (P1670
      and S970) were investigated by rheological measurements, and compared with each
      other. The effects of the gel-forming SEs on model drug (paracetamol) release
      were evaluated by in vitro drug release studies. The kinetics of the dissolution
      process were studied by analysing the dissolution data through the use of various
      kinetic equations. The results revealed that the gelling of the SEs is
      temperature- and concentration-dependent. The examined sucrose stearate (S970)
      has a stronger gel structure than that of sucrose palmitate (P1670) and this
      behaviour has a significant effect on the drug release. The analysis of the
      dissolution kinetic data in this study revealed that the dissolution follows the
      Korsmeyer-Peppas (paracetamol-P1670) or Higuchi (paracetamol-S970) equations.

PMID- 19748564
TI  - Fundamental frequency and speech intelligibility in background noise.
AB  - Speech reception in noise is an especially difficult problem for listeners with
      hearing impairment as well as for users of cochlear implants (CIs). One likely
      cause of this is an inability to 'glimpse' a target talker in a fluctuating
      background, which has been linked to deficits in temporal fine-structure
      processing. A fine-structure cue that has the potential to be beneficial for
      speech reception in noise is fundamental frequency (F0). A challenging problem,
      however, is delivering the cue to these individuals. The benefits to speech
      intelligibility of F0 for both listeners with hearing impairment and users of CIs
      are reviewed, as well as various methods of delivering F0 to these listeners.

PMID- 19748566
TI  - Mild neonatal hypoxia-ischemia induces long-term motor- and cognitive impairments
      in mice.
AB  - To understand and potentially treat the lifelong cognitive and motor deficits in
      humans resulting from perinatal mild cerebral hypoxic-ischemic (HI) events, valid
      animal models are of high importance. Nowadays the murine model of neonatal
      cerebral HI-injury (unilateral carotid artery occlusion followed by hypoxia) is
      applied more frequently. In the present study we investigated motor, behavioral
      and cognitive functioning in mice with mild cerebral HI-injury (45 min of
      hypoxia; HI-45) in comparison to mice exposed to severe HI (HI-75) and sham
      control mice. Lateralizing motor disturbances as measured using the cylinder
      rearing test developed in both HI-45 and HI-75 mice and was significantly more
      severe in HI-75 animals. To assess behavior and cognitive functions, we used the
      modified hole board (mHB) test in two stages. First, the ability of the animals
      to find the three food rewards in cued holes over time was determined. The
      results revealed an overall learning impairment in HI-75 mice, while HI-45 mice
      were not different from sham controls. In the second stage, a reversal test was
      performed with rewarded cylinders being non-cued and non-rewarded cylinders being
      cued. This reversal-task revealed impairments in cognitive flexibility in HI-45
      mice as compared to sham-control animals. Our data indicate that both the
      cylinder rearing task and the two stages of the mHB are suitable behavioral
      approaches to differentiate consequences of neonatal mild and severe brain damage
      on executive functioning.

PMID- 19748565
TI  - Apoptosis in Toxoplasma gondii activated T cells: the role of IFNgamma in
      enhanced alteration of Bcl-2 expression and mitochondrial membrane potential.
AB  - In the present study we addressed the question whether Toxoplasma gondii could
      promote apoptosis in T lymphocytes in the acute stage of infection. Using in vivo
      activated T cells and then culturing them for a short time, we observed
      activation-induced cell death in T. gondii infected mice. A higher level of
      activation-induced cell death (AICD) was seen in susceptible C57BL/6 mice than in
      resistant CBA/J mice following infection with the same P strain of parasite.
      Apoptosis in T cells of susceptible mice was associated with altered induction of
      Bcl-2/Bax, loss of Mitochondrial Transmembrane Potential. Both CD4+ and CD8+ T
      cells were found to be susceptible to apoptosis; CD4+ T cells were sensitive to
      Fas-mediated death whereas CD8+ T cells were insensitive to this signal. Caspase
      inhibitors had less effect on DNA fragmentation in CD4+ compared to CD8+ T cells.
      Exposure of CD4+ T cells to anti-IFNgamma mAb resulted in an increase in the
      number of T cells that were positive for anti-apoptotic molecule Bcl-2 and DiOC6,
      a cationic dye that accumulates in intact mitochondria. These changes were less
      noticeable in CD8+ T cells following treatment with anti-IFNgamma mAb. These
      findings provide further insight into the mechanisms of T cell apoptosis in T.
      gondii infection.

PMID- 19748567
TI  - Transgenic mice with astrocyte-targeted production of interleukin-6 are resistant
      to high-fat diet-induced increases in body weight and body fat.
AB  - Interleukin-6 (IL-6) is a major cytokine involved in both normal physiological
      brain functions and underlying significant neuropathology. IL-6 has been
      suggested to play a role in the control of body weight but the results are
      somewhat controversial. In this study we have challenged transgenic mice with
      astrocyte-targeted IL-6 expression (GFAP-IL6 mice) with a high-fat diet (55% kcal
      from fat) versus a control diet (10%). The results demonstrate that the GFAP-IL6
      mice are resistant to high-fat diet-induced increases in body weight and body
      fat, apparently without altering food intake and with no evidences of increased
      sympathetic tone. The high-fat diet-induced impaired responses to an insulin
      tolerance test (ITT), and to an oral glucose tolerance test (OGTT) in both
      genotypes. The GFAP-IL6 mice did not differ from littermate wild-type (WT) mice
      in ITT, but they were more glucose intolerant following the high-fat diet
      feeding. In summary, the present results demonstrate that brain-specific IL-6
      controls body weight which may be a significant factor in physiological
      conditions and/or in diseases causing neuroinflammation.

PMID- 19748568
TI  - Repeated restraint stress increases IgA concentration in rat small intestine.
AB  - The most abundant intestinal immunoglobulin and first line of specific
      immunological defense against environmental antigens is secretory immunoglobulin
      A. To better understand the effect of repeated stress on the secretion of
      intestinal IgA, the effects of restraint stress on IgA concentration and mRNA
      expression of the gene for the alpha-chain of IgA was assessed in both the
      duodenum and ileum of the rats. Restraint stress induced an increase in
      intestinal IgA, which was blocked by an adrenalectomy, suggesting a role of
      catecholamines and glucocorticoids. Whereas the blocking of glucocorticoid
      receptors by RU-486 did not affect the increased IgA concentration, it did reduce
      IgA alpha-chain mRNA expression in both segments, indicating a possible mediation
      on the part of glucocorticoids in IgA secretion by individual cells. Treatment
      with corticosterone significantly increased both the IgA concentration and IgA
      alpha-chain mRNA expression in ileum but not in duodenum, suggesting that
      glucocorticoids may act directly on IgA-antibody forming cells to increase IgA
      secretion in the former segment. A probable role by catecholamines was evidenced
      by the reduction in IgA concentration and IgA alpha-chain mRNA expression in both
      segments after a chemical sympathectomy with 6-hydroxydopamine (6-OHDA).
      Additionally, norepinephrine significantly reduced IgA alpha-chain mRNA levels
      but increased pIgR mRNA expression and IgA concentration in both intestinal
      segments. We propose that the increased intestinal IgA levels caused by repeated
      restraint stress is likely due to the effects of catecholamines on the transport
      of plgA across the epithelium.

PMID- 19748569
TI  - Expression of microRNAs is not related to increased expression of ZDHHC9 in hind
      leg muscles of splay leg piglets.
AB  - ZDHHC9 (zinc finger, DHHC-type containing 9) is a protein acyl transferase
      involved in palmitoylation of basic signaling molecules. We found ZDHHC9
      expression increased in hind leg muscles of newborn splay leg piglets. In order
      to elucidate the background of this increased expression we determined the
      structure of the porcine gene, including sequence variation, and analyzed the
      structure and expression of microRNAs potentially targeting the gene. We
      confirmed the expression results by RT Real-time PCR. The porcine ZDHHC9 gene has
      a similar structure to the human gene with two transcripts resulting in an
      identical protein. None of the 17 single nucleotide polymorphisms (SNPs)
      identified in the porcine gene affects the protein or putative microRNA binding
      sites, respectively. Two microRNAs (93 [minor] and 106b) were assayed in the
      muscles. Their expression variation proved to be independent from ZDHHC9
      expression thus eliminating them as causally related to congenital splay leg.

PMID- 19748570
TI  - Redox regulation of adaptive responses in skeletal muscle to contractile
      activity.
AB  - Skeletal muscle is a highly malleable tissue that responds to changes in its
      pattern of activity or the mechanical and environmental stresses placed upon it.
      The signaling pathways involved in these multiple adaptations are increasingly
      well described, but there is a lack of information on the factors responsible for
      initiating these processes. Reactive oxygen species (ROS) are produced at various
      sites in skeletal muscle and there is increasing evidence that these species play
      targeted roles in modulating redox-sensitive signaling pathways that are
      important to the muscle for making adaptations. This review will outline some of
      the processes involved and the types of experimental approaches that seem
      necessary to fully evaluate these redox signaling systems in muscle. To
      understand how labile, highly reactive ROS can play a role in cell signaling that
      is discrete and yet regulated to prevent oxidative damage, an increased knowledge
      of the subcellular localization and compartmentalization of both ROS generation
      and the redox-sensitive targets of ROS activity is required. It seems likely that
      application of this increased knowledge will lead to new approaches to
      manipulating muscle metabolism to maintain health and prevent loss of muscle
      function in age-related diseases.

PMID- 19748571
TI  - Evidence for a plant-associated natural habitat for Cronobacter spp.
AB  - Cronobacter (Enterobacter sakazakii) species are responsible for rare cases of
      necrotising enterocolitis and bacteraemia in infants, as well as cases of
      meningitis with high case fatality rates in neonates and immunocompromised
      infants. Some physiological features, such as the production of a yellow pigment,
      the formation of a gum-like extracellular polysaccharide and the ability to
      persist in a desiccated state, suggest an environmental niche for these
      organisms. To date, the natural habitat of Cronobacter spp. remains unknown. In
      this report, the isolation and characterisation of two Cronobacter sakazakii
      strains from plant roots is described. Also, the root colonisation behaviour of
      Cronobacter strains originating from clinical and plant sources is assessed. The
      nine strains investigated showed features often found in plant-associated and
      rhizosphere microorganisms, including solubilisation of mineral phosphate and
      production of indole acetic acid. Siderophore production was observed for all
      except one strain. In addition, the capability to endophytically colonise tomato
      and maize roots was demonstrated for several strains, either by fluorescence in
      situ hybridisation, using fluorescently labelled oligonucleotide probes, or by
      using strains tagged with green fluorescent protein and confocal laser scanning
      microscopy. The results provide evidence that plants may be the natural habitat
      of Cronobacter spp.

PMID- 19748572
TI  - Collated mutations in mitochondrial DNA (mtDNA) depletion syndrome (excluding the
      mitochondrial gamma polymerase, POLG1).
AB  - These tables list both published and a number of unpublished mutations in genes
      associated with early onset defects in mitochondrial DNA (mtDNA) maintenance
      including C10orf2, SUCLG1, SUCLA2, TYMP, RRM2B, MPV17, DGUOK and TK2. The list
      should not be taken as evidence that any particular mutation is pathogenic. We
      have included genes known to cause mtDNA depletion, excluding POLG1, because of
      the existing database (http://tools.niehs.nih.gov/polg/). We have also excluded
      mutations in C10orf2 associated with dominant adult onset disorders.

PMID- 19748573
TI  - Determination of mechanical stress distribution in Drosophila wing discs using
      photoelasticity.
AB  - Morphogenesis, the process by which all complex biological structures are formed,
      is driven by an intricate interplay between genes, growth, as well as intra- and
      intercellular forces. While the expression of different genes changes the
      mechanical properties and shapes of cells, growth exerts forces in response to
      which tissues, organs and more complex structures are shaped. This is exemplified
      by a number of recent findings for instance in meristem formation in Arabidopsis
      and tracheal tube formation in Drosophila. However, growth not only generates
      forces, mechanical forces can also have an effect on growth rates, as is seen in
      mammalian tissues or bone growth. In fact, mechanical forces can influence the
      expression levels of patterning genes, allowing control of morphogenesis via
      mechanical feedback. In order to study the connections between mechanical stress,
      growth control and morphogenesis, information about the distribution of stress in
      a tissue is invaluable. Here, we applied stress-birefringence to the wing
      imaginal disc of Drosophila melanogaster, a commonly used model system for organ
      growth and patterning, in order to assess the stress distribution present in this
      tissue. For this purpose, stress-related differences in retardance are measured
      using a custom-built optical set-up. Applying this method, we found that the
      stresses are inhomogeneously distributed in the wing disc, with maximum
      compression in the centre of the wing pouch. This compression increases with wing
      disc size, showing that mechanical forces vary with the age of the tissue. These
      results are discussed in light of recent models proposing mechanical regulation
      of wing disc growth.

PMID- 19748574
TI  - Multiple approaches to pharmaceutical polymorphism investigation--a case study.
AB  - Polymorph screening of Compound A, an investigational drug, revealed two
      anhydrous polymorphs (Forms I and II) and two monohydrates (Forms III and IV) of
      this pharmaceutical solid. The physiochemical properties of the four forms were
      characterized by thermal analysis, hot-stage microscopy, equilibrium solubility
      and intrinsic dissolution rate measurements, and X-ray powder diffraction. Inter
      conversion relationship of the four forms was fully elucidated. Thermodynamic
      stability relationship was inferred from melting data for Form I and Form II and
      evaluated by van't Hoff plot for Form III and Form IV. Form I and Form III were
      found to be the more stable anhydrous and hydrate form, respectively. Anhydrous
      Form I was selected for further pharmaceutical development.

PMID- 19748575
TI  - Inhibition of nucleoside transport and synergistic potentiation of methotrexate
      cytotoxicity by cimicifugoside, a triterpenoid from Cimicifuga simplex.
AB  - Cimicifugoside, a triterpenoid isolated from Cimicifuga simplex, which has been
      used as a traditional Chinese medicine due to its anti-inflammatory, analgesic or
      anti-pyretic action, was examined for inhibition of nucleoside transport and
      synergistic potentiation of methotrexate cytotoxicity. Cimicifugoside inhibited
      uptake of uridine, thymidine and adenosine in human leukemia U937 cells with the
      low nanomolar IC(50) values, but did not affect that of uracil, leucine or 2
      deoxyglucose at <or=100 nM. Cimicifugoside analogs differentially inhibited
      uridine uptake in the order cimicifugoside>cimicifugenin (aglycon of
      cimicifugoside)>bugbanoside B>cimicifugenin A, O-methyl cimicifugenin and
      bugbanoside A. Cimicifugoside had less affinity for the binding site of
      nitrobenzylthioinosine (typical high-affinity inhibitor of equilibrative
      nucleoside transporter-1) in U937 cells, K562 cells and human erythrocyte
      membranes compared with the prototype nucleoside transport inhibitor
      dipyridamole. Cimicifugoside markedly potentiated methotrexate cytotoxicity in a
      culture of U937 cells and human carcinoma KB cells. Potentiation of methotrexate
      cytotoxicity by cimicifugoside analogs in U937 cells was in proportion to their
      inhibitory activity against uridine uptake. The present study demonstrates that
      cimicifugoside is a novel specific nucleoside transport inhibitor that displays
      synergistic potentiation of methotrexate cytotoxicity.

PMID- 19748576
TI  - Brainstem encephalitis following influenza vaccination: favorable response to
      steroid treatment.
AB  - We report a 44-year-old man presenting with left hemiparesis following influenza
      vaccination. The neuroimaging studies showed a large, contrast-enhancing
      brainstem lesion and multiple punctate lesions suggesting microhaemorrhages in
      both cerebral hemispheres. The patient showed a remarkable response to high dose
      steroid treatment. Detailed diagnostic studies failed to yield any results
      supporting inflammatory/demyelinating diseases, suggesting that influenza
      vaccination might have been associated with the clinical findings. Our case
      implies that vaccination might be related with a wide range of clinical
      syndromes, including brainstem encephalitis.

PMID- 19748577
TI  - Mucosal immunization with recombinant adenoviral vectors expressing murine
      gammaherpesvirus-68 genes M2 and M3 can reduce latent viral load.
AB  - Gammaherpesviruses establish life-long latent infections in their hosts. If the
      host becomes immunosuppressed, these viruses may reactivate and cause severe
      disease, and even in immunocompetent individuals the gammaherpesviruses are
      presumed to have an oncogenic potential. Murine gammaherpesvirus-68 (MHV-68) is a
      member of the Gammaherpesvirinae subfamily and represents a useful murine model
      for this category of infections, in which new vaccination strategies may
      initially be evaluated. Two attenuated variants of MHV-68 have successfully been
      used as vaccines, but the oncogenic potential of the gammaherpesvirinae speaks
      against using a similar approach in humans. DNA immunization with plasmids
      encoding the MHV-68 genes M2 or M3 caused a reduction in either acute or early
      latent viral load, respectively, but neither immunization had an effect at times
      later than 14 days post-infection. Adenovirus-based vaccines are substantially
      more immunogenic than DNA vaccines and can be applied to induce mucosal immunity.
      Here we show that a significant reduction of the late viral load in the spleens,
      at 60 days post-infection, was achieved when immunizing mice both intranasally
      and subcutaneously with adenoviral vectors encoding both M2 and M3. Additionally
      we show that M3 immunization prevented the usual development of virus-induced
      splenomegaly at 2-3 weeks post-infection. This is the first time that
      immunization with a non-replicating vaccine has lead to a significantly reduced
      viral load at time points beyond 14 days post-infection, and thus demonstrates
      that a non-replicating vaccine may successfully be employed to reduce the viral
      burden during chronic gammaherpesvirus infection.

PMID- 19748578
TI  - Liposome-encapsulated HIV-1 Gag p24 containing lipid A induces effector CD4+ T
      cells, memory CD8+ T-cells, and pro-inflammatory cytokines.
AB  - Liposomal lipid A is an effective adjuvant for the delivery of antigens and for
      the induction of both cellular and humoral immunity. In this study, we
      demonstrate that following the third immunization with HIV-1 Gag p24 encapsulated
      in liposomes containing lipid A [L(p24+LA)], central memory CD8+ T-cells were
      localized in the spleen and lymph nodes of mice while effector memory CD8+ T
      cells and effector CD4+ T-cells were found in the PBMC. Effector CD4+ T-cells
      were also detected in the spleen and lymph nodes. The predominant cytokine
      secreted from splenic lymphocytes and lymph nodes was IFN-gamma. In contrast, IL
      6 and IL-10 were the major cytokines produced from PBMC. The peptide stimulation
      indicated that the cytokine responses observed were T-cell specific. The results
      demonstrate the importance of the adjuvant liposomal lipid A for the induction of
      HIV-1 Gag p24 -specific CD8+ T-cells, effector CD4+ T-cells, and cytokines with a
      Th-1 type profile after immunization with L(p24+LA).

PMID- 19748579
TI  - The polymeric antigen BLSOmp31 confers protection against Brucella ovis infection
      in rams.
AB  - We have engineered the polymeric vaccine BLSOmp31 by decorating the highly
      immunogenic and decameric Brucella lumazine synthase with an exposed loop of the
      Brucella outer membrane protein Omp31. In the present study, we have immunized
      different groups of rams with the recombinant chimera rBLSOmp31 in two different
      adjuvants (Incomplete Freund Adjuvant-IFA and QUIL A) and with the plasmid
      pCIBLSOmp31 administered either by i.m. injection alone or by using
      electroporation. In addition, we have used a heterologous prime-boost strategy
      consisting of repeated pCIBLSOmp31 electroporation priming followed by a single
      protein boost. Both, chimera rBLSOmp31 in IFA and the prime-boost strategy
      induced the highest IgG specific antibodies with bacteriolytic activity. While
      electroporation-enhanced humoral immune responses as compared to pCIBLSOmp31
      injection alone, the highest levels of specific IFN-gamma and protection against
      bacterial challenge were achieved with prime-boost (76%) and chimera rBLSOmp31 in
      IFA (63%). Taken together these results strongly support the usefulness of the
      chimera BLSOmp31 as a vaccine against Brucella ovis in ovine brucellosis.

PMID- 19748580
TI  - Regulatory oversight of clinical trials in Africa: progress over the past 5
      years.
AB  - Randomized controlled clinical trials represent the best way to establish the
      therapeutic or preventive value of medicines. This decade has seen a strong shift
      in the location of clinical trials from industrialized countries to developing
      countries, including many in Africa. However, without independent strong
      regulatory and ethical oversight of clinical trials the safety of research
      subjects, and scientific integrity of clinical data cannot be verified. This
      article draws up a portrait of clinical trials regulation in Africa in support of
      development of priority medicines, highlights challenges and presents the
      progress made by countries under WHO guidance over the past 5 years.

PMID- 19748581
TI  - Recombinant outer membrane vesicles to augment antigen-specific live vaccine
      responses.
AB  - Release of outer membrane vesicles is a common feature of Gram negative bacteria.
      There is growing interest in the use of these vesicles in the development of
      affordable vaccines. However, to exploit their full potential a convenient system
      to generate recombinant vesicles would be highly desirable. Here, we report the
      design of a versatile system for preparation of recombinant outer membrane
      vesicles based on an engineered autotransporter. Two model vaccine antigens of
      Leishmania were expressed as fusion proteins with the transporter domain of AIDA,
      the Escherichia coli adhesin involved in diffuse adhesion. Single subcutaneous
      injections of recombinant vesicles boosted vaccine antigen-specific antibody
      responses in mice primed with live recombinant salmonella vaccines by 6-40-fold.
      The results further show an expansion of only the vaccine antigen-specific
      antibody response indicating a great potential of this approach for prime boost
      vaccination strategies.

PMID- 19748582
TI  - Specific processing of tenascin-C by the metalloprotease meprinbeta neutralizes
      its inhibition of cell spreading.
AB  - The metalloprotease meprin has been implicated in tissue remodelling due to its
      capability to degrade extracellular matrix components. Here, we investigated the
      susceptibility of tenascin-C to cleavage by meprinbeta and the functional
      properties of its proteolytic fragments. A set of monoclonal antibodies against
      chicken and human tenascin-C allowed the mapping of proteolytic fragments
      generated by meprinbeta. In chicken tenascin-C, meprinbeta processed all three
      major splicing variants by removal of 10kDa N-terminal and 38kDa C-terminal
      peptides, leaving a large central part of subunits intact. A similar cleavage
      pattern was found for large human tenascin-C variant where two N-terminal
      peptides (10 or 15kDa) and two C-terminal fragments (40 and 55kDa) were removed
      from the intact subunit. N-terminal sequencing revealed the exact amino acid
      positions of cleavage sites. In both chicken and human tenascin-C N-terminal
      cleavages occurred just before and/or after the heptad repeats involved in
      subunit oligomerization. In the human protein, an additional cleavage site was
      identified in the alternative fibronectin type III repeat D. Whereas all these
      sites are known to be attacked by several other proteases, a unique cleavage by
      meprinbeta was located to the 7th constant fibronectin type III repeat in both
      chicken and human tenascin-C, thereby removing the C-terminal domain involved in
      its anti-adhesive activity. In cell adhesion assays meprinbeta-digested human
      tenascin-C was not able to interfere with fibronectin-mediated cell spreading,
      confirming cleavage in the anti-adhesive domain. Whereas the expression of
      meprinbeta and tenascin-C does not overlap in normal colon tissue, inflamed
      lesions of the mucosa from patients with Crohn's disease exhibited many
      meprinbeta-positive leukocytes in regions where tenascin-C was strongly induced.
      Our data indicate that, at least under pathological conditions, meprinbeta might
      attack specific functional sites in tenascin-C that are important for its
      oligomerization and anti-adhesive activity.

PMID- 19748583
TI  - Metabolism of stanozolol: chemical synthesis and identification of a major canine
      urinary metabolite by liquid chromatography-electrospray ionisation ion trap mass
      spectrometry.
AB  - The canine phase I and phase II metabolism of the synthetic anabolic-androgenic
      steroid stanozolol was investigated following intramuscular injection into a male
      greyhound. The major phase I biotransformation was hydroxylation to give 6alpha
      hydroxystanozolol which was excreted as a glucuronide conjugate and was
      identified by comparison with synthetically derived reference materials. An
      analytical procedure was developed for the detection of this stanozolol
      metabolite in canine urine using solid phase extraction, enzyme hydrolysis of
      glucuronide conjugates and analysis by positive ion electrospray ionisation ion
      trap LC-MS.

PMID- 19748584
TI  - Glycerol kinase activity and glycerol kinase-3 gene are up-regulated by
      acclimation to 5 degrees C in diapause eggs of the silkworm, Bombyx mori.
AB  - With initiation of diapause, glycogen is converted into sorbitol and glycerol in
      eggs of the silkworm Bombyx mori. At diapause termination promoted by incubation
      at 5 degrees C, sorbitol and glycerol are utilized. Although sorbitol utilization
      is triggered by NAD-sorbitol dehydrogenase induced by acclimation to 5 degrees C,
      the initial enzyme utilizing glycerol remains unclear. In this study, we detected
      glycerol kinase activity in diapause-terminated eggs and then characterized its
      properties; maximal activity was seen at pH 8.5-9.0, and Km values for glycerol
      and ATP were 0.32 and 0.095 mM, respectively. In diapause eggs continuously kept
      at 25 degrees C, the activity was almost negligible. However, activity was seen
      after chilling for 60 days and thereafter increased when the eggs were exposed to
      5 degrees C after 2 days post-oviposition, indicating that glycerol kinase is a
      rate-limiting enzyme in glycerol utilization. We then cloned cDNAs encoding
      glycerol kinase-1, -2 and -3 from B. mori. Only gene expression of glycerol
      kinase-3 was up-regulated in diapause eggs exposed to 5 degrees C, indicating
      that glycerol kinase activity is regulated via transcription of the glycerol
      kinase-3 gene.

PMID- 19748585
TI  - The adipokinetic hormone system in Culicinae (Diptera: Culicidae): molecular
      identification and characterization of two adipokinetic hormone (AKH) precursors
      from Aedes aegypti and Culex pipiens and two putative AKH receptor variants from
      A. aegypti.
AB  - Insect neuropeptides of the adipokinetic hormone (AKH) family induce the
      mobilization of energy stores to fuel flight, but also affect the nutritional
      balance during diapause and oogenesis. They are therefore important regulators
      for flight, hibernation, and reproduction in mosquitoes including those that
      transmit human pathogens. In this study, we identified and analyzed the genes
      encoding two AKH preprohormones in the Yellow fever mosquito, Aedes aegypti:
      Aedae-AKH-I encodes the octapeptide pELFTPSWa and Aedae-AKH-II the decapeptide
      pEVTFSRDWNAa. Identical AKHs were identified in the West Nile virus vector, Culex
      pipiens, whose genes were characterized in this study as Culpi-AKH-I and Culpi
      AKH-II. Using Northern blot, transcript expression was shown in A. aegypti, for
      Aedae-AKH-I in the head/thorax tissues of pupae and females, as well as in the
      abdomen of adult males; Aedae-AKH-II was only expressed in adults. In an
      immunocytological study using an AKH-antibody, the corpus cardiacum (CC), the
      intrinsic CC-cells (X-cells), the nervi corporis cardiaci, cells in the brain and
      thoracic ganglia were stained. In addition, two splice variants of the AKH
      receptor gene were characterized in A. aegypti, (Aedae-AKHR-I and -II). RT-PCR
      revealed that both variants of these typical G-protein-coupled receptors were
      expressed in all life stages. Aedae-AKHR-I expression was also detected in the
      ovaries, indicating once more the influence of the AKH/AKHR system during the
      insect's oogenesis. Based on phylogenetic data, we postulate two closely related
      types of AKH-receptors that could bind selectively the two AKH peptides found in
      A. aegypti.

PMID- 19748586
TI  - Steering orally induced deviation of xenogeneic immunity with exogenous cytokines
      in rats fed porcine proteins.
AB  - Immune response to xenoantigens is a barrier to xenotransplantation. The
      objective of this study was to determine if rat cell-mediated immunity (CMI) and
      antibody (Ab) to discordant porcine xenoantigens could be suppressed by oral
      administration of porcine protein with adjunct systemic cytokine therapy. Based
      on principles of oral tolerance, it was hypothesized that: a. Feeding proteins
      from porcine blood mononuclear cells (PBMC) would induce a type 2 response,
      inhibiting CMI and type 1 Ab (associated with xenograft rejection) but increasing
      the amount of type 2 Ab. b. IL-4, a type 2 cytokine would exaggerate type 2 bias,
      enhancing immune deviation. c. IFN-gamma, a type 1 cytokine was expected to down
      regulate overall Ab production, but increase CMI and type 1 Ab. DA rats fed
      porcine proteins with or without subcutaneous and intraperitoneal injections of
      IFN-gamma or IL-4 received PBMC by subcutaneous injection. Dermal delayed-type
      hypersensitivity to PBMC was the indicator of CMI. The IgG Ab to porcine proteins
      was quantified and type 2 (IgG(1)+IgG(2a)) to type 1 (IgG(2b)) Ab ratios
      indicated IR bias. Unfed, PBMC-challenged controls had a type 1 response bias but
      feeding PBMC induced a type 2 bias that suppressed CMI and type 1 Ab and
      increased type 2 Ab but not total IgG Ab. Contrary to the T(H)1/T(H)2 paradigm,
      IL-4 decreased oral-induced type 2 IR deviation and did not provide significant
      benefits relative to feeding alone. Treatment with IFN-gamma prevented a switch
      to type 2 IR but feeding-induced suppression of CMI was not significantly
      compromised. The IFN-gamma potently suppressed Ab, including, surprisingly, type
      1 IgG isotypes. Contrary to the hypothesis tested, feeding Ag in combination with
      systemic delivery of recombinant IFN-gamma apparently created an immunoregulatory
      environment most favorable to xenograft survival.

PMID- 19748588
TI  - Enhancement of non-specific immune response in sea cucumber (Apostichopus
      japonicus) by Astragalus membranaceus and its polysaccharides.
AB  - In this study, the immunostimulatory effect of oral administration of different
      preparations (conventional fine powder [CP] and superfine powder [SP]) of
      Astragalus membranaceus root or its polysaccharides (APS) in sea cucumber
      (Apostichopus japonicus) was investigated. Sea cucumbers with an average initial
      weight of 49.3 +/- 5.65 g were fed with a diet containing 3% CP or SP or 0.3% APS
      over a period of 60 days. The non-specific humoral (phenoloxidase, lysozyme and
      agglutination titer) and cellular (phagocytic capacity and reactive oxygen
      species) responses were determined and compared with controls (no supplement)
      after 20, 40 and 60 days of feeding. Variation in the levels of responses was
      evident among different supplements. SP and APS significantly enhanced most of
      the immune parameters tested. Among the humoral responses, lysozyme activity
      significantly increased after feeding with SP-supplemented diet for 20, 40 or 60
      days. Furthermore, lectin titer showed significant enhancement after 20 and 60
      days of feeding with APS-supplemented diet. Significant increase in the
      production of reactive oxygen species was evident for all three supplements after
      20 days of feeding, but no significant change in serum phenoloxidase activity was
      observed for any of the three supplements over the three different periods.
      Overall, significant modulation of the cellular responses was only noticed after
      20 days of feeding with SP- or APS-supplemented diet. After 60 days, these two
      groups also exhibited a decrease in the cumulative symptom rates compared to the
      controls when challenged with Vibrio splendidus. These results indicated that
      dietary intake containing A. membranaceus root or its polysaccharides could
      enhance the immune responses of A. japonicus and improve its resistance to
      infection by V. splendidus.

PMID- 19748589
TI  - Tiger shrimp (Penaeus monodon) penaeidin possesses cytokine features to promote
      integrin-mediated granulocyte and semi-granulocyte adhesion.
AB  - Recent studies indicated that antimicrobial peptides (AMPs) play multiple roles
      in both innate and adaptive immune functions. The penaeidin of tiger shrimp
      Penaeus monodon shows an antimicrobial activity against Gram-positive bacteria
      and filamentous fungi. To study immunomodulation functions of the penaeidin, we
      transfected shrimp hemocytes in primary culture with penaeidin-specific small
      interfering RNA (siRNA-3) and observed a concomitant 20% reduction in adhesive
      hemocytes compared with mock-transfected cells. The addition of biosynthesized or
      chemically synthesized penaeidin or penaeidin proline-rich domain (PRD) to the
      culture medium of penaeidin knock-down hemocytes led to a full recovery in the
      number of adhesive hemocytes. The effect of penaeidin knock-down on the
      expression of tiger shrimp cell adhesion-associated molecules was examined using
      real-time Q-PCR. Results demonstrated 91% and 64% decreases in the expression of
      integrin-beta and collagen, respectively, and a 396% increase in the expression
      of collagenase. The addition of chemically synthesized penaeidin after penaeidin
      knock-down hemocytes normalized the expression of these genes. The addition of
      the integrin-beta ligand competitor RGDS to mock-transfected hemocytes decreased
      the number of adhesive hemocytes similar to penaeidin knock-down. In conclusion,
      penaeidin possesses an integrin-beta-mediated cytokine feature that promotes
      shrimp granulocyte and semi-granulocyte adhesion. This is the first report about
      functional shrimp cytokine.

PMID- 19748590
TI  - Determination of enzymatic source of alanine aminotransferase activity in serum
      from dogs with liver injury.
AB  - INTRODUCTION: Increase of serum alanine aminotransferase (ALT) activity is widely
      used as a surrogate marker for tissue damage. Two ALT isoforms, ALT1 and ALT2,
      have been cloned recently in mammals. The study investigated the source of
      elevated ALT activity in serum of dogs treated with a hepatotoxic compound.
      METHODS: ALT activity was measured by enzyme assay. Immunoblot analysis was
      performed using generated specific peptide antibodies against dog ALTs. LC-MS/MS
      based proteomics analysis was conducted to independently identify dog ALT
      peptides. Serum samples immunodepleted of major serum components by Seppro IgY
      D11 microbead spin column were evaluated by the immunoblot analysis, and compared
      with those of the ALT activity. RESULTS: Involvement of ALT enzyme(s) is
      consistent with the following observations: 1) all the substrates (L-alanine and
      alpha-ketoglutarate) were required for serum ALT activity as purified porcine
      ALT1 needed for activity, 2) serum ALT activity was inhibited by L-cycloserine, a
      known ALT inhibitor, and 3) apparent Km value for the ALT reaction catalyzed by
      the serum, liver, and skeletal muscle was roughly similar. Immunoblot analysis
      showed that ALT1 was detected in liver and both ALTs were detected in the
      skeletal muscle. The relative expression level of ALTs was -: liver ALT1>skeletal
      muscle ALT1>skeletal muscle ALT2. LC-MS/MS-based proteomics analysis gave similar
      results. Immunoblot analysis of the depleted serum samples revealed the presence
      of ALT1 in compound-treated dogs. Intensity of the ALT1 band detected in the sera
      correlated well with the ALT activity measured by the enzyme assay. DISCUSSION:
      Based on these findings, we conclude that the elevation of serum ALT activity in
      dogs with liver injury is attributed to elevation of ALT1 protein level in serum.
      The methodology to directly detect ALT proteins in serum could be a tool to
      facilitate our understanding of biological and toxicological significance of the
      ALT isoenzymes.

PMID- 19748587
TI  - The construction of a cDNA library enriched for immune genes and the analysis of
      7535 ESTs from Chinese mitten crab Eriocheir sinensis.
AB  - Chinese mitten crab Eriocheir sinensis is one of the most important aquaculture
      crustacean species in China. A cDNA library was constructed from hemocytes of E.
      sinensis challenged with the mixture of Listonella anguillarum and Staphylococcus
      aureus, and randomly sequenced to collect genomic information and identify genes
      involved in immune defense response. Single-pass 5' sequencing of 10368 clones
      yielded 7535 high quality ESTs (Expressed Sequence Tags) and these ESTs were
      assembled into 2943 unigenes. BLAST analysis revealed that 1706 unigenes (58.0%
      of the total) or 4593 ESTs (61.0% of the total) were novel genes that had no
      significant matches to any protein sequences in the public databases. The rest
      1237 unigenes (42.0% of the total) were closely matched to the known genes or
      sequences deposited in public databases, which could be classed into 20 or 23
      classifications according to "molecular function" or "biological process"
      respectively based on the Gene Ontology (GO). And 221 unigenes (7.5% of all 2943
      unigenes, 17.9% of matched unigenes) or 969 ESTs (12.9% of all 7535 ESTs, 32.9%
      of matched ESTs) were identified to be immune genes. The relative higher
      proportion of immune-related genes in the present cDNA library than that in the
      normal library of E. sinensis and other crustaceans libraries, and the
      differences and changes in percentage and quantity of some key immune-related
      genes especially the immune inducible genes between two E. sinensis cDNA
      libraries may derive from the bacteria challenge to the Chinese mitten crab. The
      results provided a well-characterized EST resource for the genomics community,
      gene discovery especially for the identification of host-defense genes and
      pathways in crabs as well as other crustaceans.

PMID- 19748591
TI  - N-Nitrosopiperidine and N-Nitrosodibutylamine induce apoptosis in HepG2 cells via
      the caspase dependent pathway.
AB  - The human hepatoma cell line (HepG2) exhibited a dose and time-dependent
      apoptotic response following treatment with N-Nitrosopiperidine (NPIP) and N
      Nitrosodibutylamine (NDBA), two recognized human carcinogens. Our results showed
      a significant apoptotic cell death (95%) after 24h treatment with NDBA (3.5 mM),
      whereas it was necessary to use high doses of NPIP (45 mM) to obtain a similar
      percentage of apoptotic cells (86%). In addition, both extrinsic (caspase-8) and
      intrinsic pathway (caspase-9) could be implicated in the N-Nitrosamines-induced
      apoptosis. This study also addresses the role of reactive oxygen species (ROS) as
      intermediates for apoptosis signaling. A significant increase in ROS levels was
      observed after NPIP treatment, whereas NDBA did not induce ROS. However, N
      acetylcysteine (NAC) did not block NPIP-induced apoptosis. All these findings
      suggest that NPIP and NDBA induce apoptosis in HepG2 cells via a pathway that
      involves caspases but not ROS.

PMID- 19748592
TI  - Seventh Annual International Umbilical Cord Blood Transplantation Symposium, Los
      Angeles, California, June 5-6, 2009.

PMID- 19748593
TI  - A pharmacokinetic study of plerixafor in subjects with varying degrees of renal
      impairment.
AB  - Plerixafor is a selective antagonist of CXCR4 used for mobilization of
      hematopoietic stem cells (HSCs) for autologous stem cell transplantation (SCT) in
      patients with multiple myeloma (MM) and non-Hodgkin lymphoma (NHL). This Phase 1
      open-label study in healthy subjects was conducted to evaluate the
      pharmacokinetic characteristics of plerixafor in subjects with renal impairment.
      All subjects received a single 0.24 mg/kg subcutaneous dose of plerixafor.
      Subjects were stratified into 4 cohorts based on creatinine clearance determined
      from a 24-hour urine collection: control (>90 mL/min), mild renal impairment (51
      80 mL/min), moderate renal impairment (31-50 mL/min), and severe renal impairment
      (<31 mL/min, not requiring dialysis). Eleven female subjects (48%) and 12 male
      subjects (52%), ranging in age from 35 to 73 years, were enrolled. Plerixafor
      clearance was reduced in subjects with renal impairment and was positively
      correlated with creatinine clearance. The mean area under the concentration-
      versus-time curve from time 0 to 24 hours postdose of plerixafor in subjects with
      mild, moderate, and severe renal impairment was 7%, 32%, and 39% higher,
      respectively, than that in subjects with normal renal function. Renal impairment
      had no effect on maximal plasma concentrations. The safety profile was similar
      among subjects with renal impairment and controls. No renal impairment-related
      trends in the incidence of adverse events were apparent. A plerixaflor dose
      reduction to 160 microg/kg in patients with a creatinine clearance value <or= 50
      mL/min is expected to result in exposure similar to that in patients with normal
      to mildly impaired renal function.

PMID- 19748594
TI  - Nutritional epidemiology in the context of nitric oxide biology: a risk-benefit
      evaluation for dietary nitrite and nitrate.
AB  - The discovery of the nitric oxide (NO) pathway in the 1980s represented a
      critical advance in understanding cardiovascular disease, and today a number of
      human diseases are characterized by NO insufficiency. In the interim, recent
      biomedical research has demonstrated that NO can be modulated by the diet
      independent of its enzymatic synthesis from l-arginine, e.g., the consumption of
      nitrite- and nitrate-rich foods such as fruits, leafy vegetables, and cured meats
      along with antioxidants. Regular intake of nitrate-containing food such as green
      leafy vegetables may ensure that blood and tissue levels of nitrite and NO pools
      are maintained at a level sufficient to compensate for any disturbances in
      endogenous NO synthesis. However, some in the public perceive that dietary
      sources of nitrite and nitrate are harmful, and some epidemiological studies
      reveal a weak association between foods that contain nitrite and nitrate, namely
      cured and processed meats, and cancer. This paradigm needs revisiting in the face
      of undisputed health benefits of nitrite- and nitrate-enriched diets. This review
      will address and interpret the epidemiological data and discuss the risk-benefit
      evaluation of dietary nitrite and nitrate in the context of nitric oxide biology.
      The weak and inconclusive data on the cancer risk of nitrite, nitrate and
      processed meats are far outweighed by the health benefits of restoring NO
      homeostasis via dietary nitrite and nitrate. This risk/benefit balance should be
      a strong consideration before there are any suggestions for new regulatory or
      public health guidelines for dietary nitrite and nitrate exposures.

PMID- 19748595
TI  - Fasting suppresses T cell-mediated immunity in female Mongolian gerbils (Meriones
      unguiculatus).
AB  - Immune defense is important for organisms' survival and fitness. Small mammals in
      temperate zone often face seasonal food shortages. Generally fasting can suppress
      immune function in laboratory rodents and little information is available for
      wild rodents. The present study tested the hypothesis that Mongolian gerbils
      (Meriones unguiculatus) could inhibit T cell-mediated immunity to adapt to acute
      fasting. Forty-two females were divided into the fed and fasted groups, in which
      the latter was deprived of food for 3days. After 66h fasting, half of the gerbils
      in each group were injected with phosphate buffered saline or phytohaemagglutinin
      (PHA) solution. T cell-mediated immunity assessed by PHA response was suppressed
      in the fasted gerbils compared with the fed gerbils. The fasted gerbils had lower
      body fat mass, wet and dry thymus mass, dry spleen mass, white blood cells, serum
      leptin and blood glucose concentrations, but higher corticosterone concentrations
      than those of the controls. Moreover, PHA response was positively correlated with
      body fat mass and serum leptin levels in the immunochallenged groups. Taken
      together, acute fasting leads to immunosuppression, which might be caused by low
      body fat mass and low serum leptin concentrations in female Mongolian gerbils.

PMID- 19748596
TI  - Molecular characterization of the major yolk protein of the Japanese common sea
      cucumber (Apostichopus japonicus) and its expression profile during ovarian
      development.
AB  - The most abundant protein in the coelomic fluid of the Japanese common sea
      cucumber (Apostichopus japonicus) was purified through two steps of liquid
      chromatography. Subsequent peptide sequencing and cDNA cloning demonstrated that
      the purified fraction contained two similar but distinct proteins. Deduced amino
      acid sequences of these proteins revealed about 30% identity with those of sea
      urchin major yolk protein (MYP) and therefore they were designated AjMYP1 and
      AjMYP2. The full-length cDNAs for AjMYP1 and AjMYP2 consisted of 4600 and 4420bp,
      with predicted protein lengths of 1365 and 1345 amino acid residues,
      respectively. RT-PCR detected transcripts for both types of AjMYPs in all the
      tissues and organs examined. The transcript levels of both AjMYPs in the ovary
      were apparently elevated at late stages of ovarian development whereas the MYP
      content of the ovary examined by SDS-PAGE remained stable throughout ovarian
      development.

PMID- 19748597
TI  - The effect of ovarian steroids on oxytocin-stimulated secretion and synthesis of
      prostaglandins in bovine myometrial cells.
AB  - The aim was to study whether bovine myometrial cells have an enzymatic system
      able to produce prostaglandins (PGs) and whether PGs synthesis is regulated by
      steroids in a similar manner as endometrial cells. In Experiment 1,
      immunohistochemical studies localized proteins for cyclooxygenase 2 (COX2), PGE
      synthase (PGES) and PGF2alpha synthase (PGFS) in myometrial and endometrial (as
      positive control) slices from days 14 to 16 of the estrous cycle. Enzymatically
      isolated myometrial cells (2.5 x 10(5)/ml) were cultured for 96 h to attach them
      to the bottom of the culture well. In Experiment 2, cells were preincubated for
      30 min with progesterone (P4; 10(-5) M), and thereafter incubated for 4 or 6h
      with arachidonic acid (AA; 10(-5) M, as positive control), oxytocin (OT; 10(-7)
      M), and OT+P4. In medium, PGE and PGFM (PGF2alpha metabolite) were increased
      (P<0.05) by AA treatment after 4 and 6h, but by OT only after 6h of incubation.
      Progesterone did not affect (P>0.05) basal secretion of both PGs, but it
      diminished (P<0.05) the stimulatory effect of OT on PGF2alpha and PGE secretion
      after 6h of incubation. The amount of enzyme protein for COX2, PGES and PGFS
      analyzed by Western Blot was affected (P>0.05) by any of the factors added to the
      culture medium. In Experiment 3, myometrial cells were preincubated with P4 (10(
      5)M) and pregnenolone (P5; 10(-5)M) for 30 min, and then incubated for 6h with OT
      (10(-7) M) and OT plus each of these steroids used. Expression of mRNA for COX2,
      but not PGFS and PGES, was found in the cells stimulated with OT. Neither P4 nor
      P5 affected expression of the studied genes; however, both steroids diminished
      (P<0.05) OT-stimulated mRNA expression of COX2. The data suggest that: (a)
      myometrial cells are able to synthesize both PGF2alpha and PGE and (b) synthesis
      of these PGs may be regulated by steroids through a transcription-independent
      manner, which modulated the effect of OT on COX2 mRNA expression.

PMID- 19748598
TI  - Image of the month. Pancreaticoduodenal artery and superior mesenteric artery
      pseudoaneurysm associated with hemosuccus pancreaticus.

PMID- 19748599
TI  - Serum levels of IL-8 and IL-6 in the long term pulmonary complications induced by
      sulfur mustard: Sardasht-Iran Cohort Study.
AB  - Sulfur mustard (SM) is a blistering chemical agent which has short and long term
      toxicity against many organs. The respiratory tract is one of the main targets,
      and is the most disabling long term complication of SM. Inflammatory mediators
      especially IL-8 and IL-6 play the primary role in the various chronic pulmonary
      diseases. Sardasht-Iran Cohort Study (SICS) was designed to evaluate
      immunological and molecular parameters in SM exposed people 20 years after
      exposure. In the present study, the association of the serum levels of IL-8, IL
      6, C reactive protein (CRP) and rheumatoid factor (RF) with long term pulmonary
      involvement was evaluated. There were 348 exposed and 120 control participants.
      The clinical evaluations were done for all subjects and Spirometry was performed
      according to American Thoracic Society Criteria. Severity of pulmonary
      involvement was assessed by Global Initiative for chronic Obstructive Lung
      Disease (GOLD) classification. The serum levels of IL-8, IL-6 and RF were
      assessed by ELISA assay. CRP was assessed by photometric method. The serum levels
      of IL-8 and IL-6 significantly decreased in the SM exposed participants compared
      to the control group. There were no significant associations between the serum
      levels of IL-8 and pulmonary symptoms (chronic cough, sputum, hemoptysis, and
      dyspnea), pulmonary findings (crackles, rales, and wheezing) as well as
      spirometry parameters. IL-6 was associated with wheezing and CRP was associated
      with wheezing and rales in SM exposed group. We concluded the serum levels of
      these inflammatory mediators probably do not have any major role in pathogenesis
      and persistence of pulmonary complications and do not reflect the degree of
      severity of pulmonary involvement following SM exposure.

PMID- 19748600
TI  - Foreword to special issue: spinal cord injury-neuroplasticity and recovery of
      respiratory function.

PMID- 19748601
TI  - The UK Biobank project: trust and altruism are alive and well: a model for
      achieving public support for research using personal data.

PMID- 19748602
TI  - Determinants of wound infections for breast procedures: assessment of the risk of
      wound infection posed by an invasive procedure for subsequent operation.
AB  - OBJECTIVE: Wound infection remains a major source of postoperative morbidity
      leading to prolonged hospital stays and increased total cost, including indirect
      expenses related to the wound infection. We examined whether there is any higher
      risk of wound infection in patients undergo a reoperation after an initial
      operation or excision/incision biopsy. METHODS AND RESULTS: A retrospective
      review of medical charts of patients with breast operations between January 1990
      and July 2008 was carried out. The overall incidence of wound infection was 18.2%
      (231/1267). The rate of wound infection was (32%) when reoperation was done after
      previous modified radical mastectomy, 18.9% and 16.8% when the previous
      operations were lumpectomy/segmenectomy with axillary dissection and simple
      mastectomy without axillary dissection, respectively and (10.8%) when reoperation
      was performed after previous biopsy. Reoperation involving axillary dissection
      was associated with significantly higher rates of wound infection (p<0.01).
      Antibiotic prophylaxis continued into the postoperative period was associated
      with significantly decreased rate of wound infection (p<0.01). CONCLUSIONS:
      Initial procedure affects the risk of wound infection in subsequent operation in
      patients with breast cancer. Significantly higher risks of wound infection are
      seen in those patients who had undergone axillary dissection or modified radical
      mastectomy.

PMID- 19748603
TI  - Effect of surfactant on the production of oxygenated unsaturated fatty acids by
      Bacillus megaterium ALA2.
AB  - Bacillus megaterium ALA2 NRRL B-21660 has been well studied for the production of
      many oxygenated unsaturated fatty acids from linoleic acid. Its major product,
      12,13,17-trihydroxy-9(Z)-octadecenoic acid (12,13,17-THOA), inhibited the growth
      of many plant pathogenic fungi. However, we have been unable, until now, to
      demonstrate 12,13,17-THOA production in a fermentor. Here, we have investigated
      the effect of surfactants on 12,13,17-THOA production. Surfactant types (SO-25,
      Tween-80 and Triton X-100) at various concentrations were evaluated for their
      effects on cell growth and production of 12,13,17-THOA. Triton X-100 decreased
      cell growth and 12,13,17-THOA production while 1% Tween-80 increased 12,13,17
      THOA production more than twofold over control. In a pH and dissolved oxygen (DO)
      controlled fermentor and with 1.0% Tween-80, both 12,13,17-THOA production and
      productivity increased to 553 mg/L and 24.0mg/L/hour, respectively. We further
      conducted THOA production in a fermentor without the control of pH and DO, but
      with aeration through medium surface rather than by Spurger, and with various
      amounts of Tween-80 to compare with the results obtained in flask runs. Both
      additions with 0.1% and 0.5% Tween-80 and the control runs produced poor amounts
      of product 12,13,17-THOA. The maximum 12,13,17-THOA production was observed at
      1.0% Tween-80 at a yield of 650 mg/L. Thus fermentor production of 12,13,17-THOA
      was successfully demonstrated.

PMID- 19748604
TI  - Isolation of a Methylobacillus sp. that degrades microcystin toxins associated
      with cyanobacteria.
AB  - Sludge from cyanobacteria-salvaged yard in Meiliang Bay, Lake Taihu in Wuxi,
      China was cultured and acclimated by inoculating microcystins (MCs) extract.
      Strain J10 was isolated by degrading the MC-RR and MC-LR and was identified as
      Methylobacillus sp. Further research showed that both MC-LR and MC-RR could be
      completely degraded at 17h after inoculation of J10, and the degradation probably
      was mediated by oxygen. Different enzymes, oxygen-dependent as well as oxygen
      independent, with MC-degrading activity were found in the different fractions of
      J10 culture. However, the enzymes mainly responsible for MC degradation by J10
      were oxygen-dependent and were probably bound to cell wall or outside the
      cytoplasmic membrane.

PMID- 19748606
TI  - Nuclear factor of activated T cells mediates fluid shear stress- and tensile
      strain-induced Cox2 in human and murine bone cells.
AB  - Mechanical loading such as interstitial fluid shear stress and tensile strain
      stimulates bone cells, which respond by changing bone mass and structure to
      maintain optimal skeletal architecture. Bone cells also adapt to bone implants
      and altered mechanical loading. Osseous integration between host bone and
      implants is a prerequisite for the stability of implants. Fluctuating fluid
      pressure and interfacial strains occur between bone cells and implants due to
      mechanical loading during walking and other daily activities. In this study, we
      examined the signaling mechanism by which mechanical stimulation activates a
      novel transcription factor in human and mouse bone cells. Nuclear factor of
      activated T cells (NFAT) is one of the transcription factors that act downstream
      of the Ca(++)/calcineurin (Ca(++)/Cn) network: a well-known pathway of
      inflammation. In this study, we hypothesized that NFAT2 is activated in response
      to mechanical stimulation and mediates Cox2 expression. Fluid shear stress and
      tensile strain results in nuclear translocation of NFAT in cells of the
      osteoblastic lineage. A peptide inhibitor of the Cn/NFAT axis was found to block
      the mechanical stimulation-mediated Cox2 induction. Further, chromatin
      immunoprecipitation assay shows direct interaction between NFAT2 and the human
      Cox2 promoter region. Additionally, CnAbeta knockout calvarial bone cells were
      found to be less sensitive than control bone cells to mechanical stimulation. Our
      study provides new evidence for a novel role for NFAT in bone mechanotransduction
      in the context of cytokine gene induction in bone cells.

PMID- 19748605
TI  - Nuclear functions of the HMG proteins.
AB  - Although the three families of mammalian HMG proteins (HMGA, HMGB and HMGN)
      participate in many of the same nuclear processes, each family plays its own
      unique role in modulating chromatin structure and regulating genomic function.
      This review focuses on the similarities and differences in the mechanisms by
      which the different HMG families impact chromatin structure and influence
      cellular phenotype. The biological implications of having three architectural
      transcription factor families with complementary, but partially overlapping,
      nuclear functions are discussed.

PMID- 19748607
TI  - Mechanical loading regimes affect the anabolic and catabolic activities by
      chondrocytes encapsulated in PEG hydrogels.
AB  - OBJECTIVE: Mechanical loading of cell-laden synthetic hydrogels is one strategy
      for regenerating functional cartilage. This work tests the hypothesis that type
      of loading (continuous vs intermittent) and timing when loading is applied
      (immediate vs delayed) influence anabolic and catabolic activities of
      chondrocytes when encapsulated in poly(ethylene glycol) (PEG) hydrogels. METHODS:
      Primary bovine chondrocytes encapsulated in PEG hydrogels were subjected to
      unconfined dynamic compressive strains applied continuously or intermittently for
      1 week (i.e., immediate) or intermittently for 1 week but after a 1 week free
      swelling (FS) period (i.e., delayed). Anabolic activities were assessed by gene
      expression for collagen II and aggrecan (AGC) and extracellular matrix (ECM)
      deposition by (immuno)histochemistry. Catabolic activities were assessed by gene
      expression for matrix metalloproteinases, MMP-1, 3, and 13. RESULTS: Intermittent
      loading (IL) upregulated ECM and MMP expressions, e.g., 2-fold, 16-fold and 8
      fold for collagen II, MMP-1, MMP-3, respectively. Continuous loading upregulated
      AGC expression 1.5-fold but down-regulated MMP-1 (3-fold) and -3 (2-fold)
      expressions. For delayed loading, chondrocytes responded to FS conditions by down
      regulating MMP expressions (P<0.01), but were less sensitive to loading when
      applied during week 2. Spatially, deposition of ECM molecules was dependent on
      the timing of loading, where immediate loading favored enhanced collagen II
      deposition. CONCLUSIONS: The type and timing of dynamic loading dramatically
      influenced ECM and MMP gene expression and to a lesser degree matrix deposition.
      Our findings suggest that early applications of IL is necessary to stimulate both
      anabolic and catabolic activities, which may be important in regenerating and
      restructuring the engineered tissue long-term.

PMID- 19748608
TI  - Inhibition of cyclooxygenase-2 expression and prostaglandin E2 production in
      chondrocytes by avocado soybean unsaponifiables and epigallocatechin gallate.
AB  - OBJECTIVE: To evaluate the anti-inflammatory effect of the combination of avocado
      soybean unsaponifiables (ASU) and epigallocatechin gallate (EGCG) on
      cyclooxygenase-2 (COX-2) expression and prostaglandin E(2) (PGE(2)) production in
      cytokine-activated equine chondrocytes. METHODS: Production of type II collagen
      and aggrecan was verified by immunohistochemistry and Western blot. Chondrocytes
      were incubated with: (1) control media alone, (2) ASU (4 microg/ml; 8.3
      microg/ml), (3) EGCG (4, 40, 400 ng/ml), or (4) the combination of ASU and EGCG
      for 24h. Cells were next incubated with control medium alone or with IL-1beta (10
      ng/ml) and TNF-alpha (1 ng/ml). COX-2 gene expression by real-time PCR analysis
      and NF-kappaB nuclear translocation by immunohistochemistry were performed after
      1h of incubation. PGE(2) production was determined by immunoassay after 24h of
      incubation. RESULTS: Equine chondrocytes responded to cytokine activation by up
      regulated gene expression of COX-2 and increased PGE(2) production. Activation
      was associated with NF-kappaB translocation. Individually, ASU and EGCG
      marginally inhibited COX-2 expression and PGE(2) production in activated
      chondrocytes. In contrast, the combination of ASU and EGCG reduced COX-2
      expression close to non-activated control levels and significantly inhibited
      PGE(2) production. These reductions were statistically greater than those of ASU
      or EGCG alone. The inhibition of COX-2 expression and PGE(2) production was
      associated with inhibition of NF-kappaB translocation. CONCLUSION: The present
      study demonstrates that the anti-inflammatory activity of ASU and EGCG is
      potentiated when used in combination. This combination may offer an attractive
      supplement or alternative to non-steroidal anti-inflammatory drugs (NSAIDs) in
      the management of osteoarthritis.

PMID- 19748609
TI  - Fibroblast growth factor-2 induced chondrocyte cluster formation in
      experimentally wounded articular cartilage is blocked by soluble Jagged-1.
AB  - INTRODUCTION: Basic fibroblast growth factor (FGF2) is a mitogen for articular
      chondrocytes. Cell death frequently occurs upon cartilage wounding and is evident
      during the progression of osteoarthritis. We hypothesised that incubation of
      wounded articular cartilage with exogenously added FGF2 would enhance cartilage
      repair, replacing dead cells through increased cell proliferation. METHODS:
      Articular cartilage from the metacarapalphalangeal joint of immature bovine
      steers was wounded in situ, then incubated in vitro in the continual presence or
      absence of FGF2. Cellular proliferation was expressed as a ratio of cell density
      of a fixed area between wounded and adjacent cartilage. Immunolabelling revealed
      the incorporation of bromodeoxyuridine and localisation of collagen type VI and
      Notch1 epitopes. gamma-secretase inhibitor N-[N-(3,5-Difluorophenacetyl-L
      alanyl)]-S-phenylglycine t-butyl ester and soluble Jagged1 ligand (sJ1) were used
      to analyse the function of Notch signalling in this wound model. RESULTS: FGF2
      induced cellular proliferation at the margins of wounded articular cartilage,
      where proliferative chondrocytes adopted a cluster configuration. Collagen type
      VI protein was expressed by chondrocytes in clusters, as was Notch1. Cellular
      proliferation was not affected by inhibition of gamma-secretase dependent Notch1
      signalling. Binding of sJ1 to Notch1 receptors in FGF2 treated cartilage
      inhibited proliferation. CONCLUSION: Addition of FGF2 induces rapid chondrocyte
      proliferation in wounded cartilage, chondrocytes adopt a cluster morphology and
      also express Notch1. Binding of sJ1 to Notch1 causes apoptosis overriding a
      proliferative response. This study may shed some light on the significance of
      increased Notch1 expression and its localisation in chondrocyte clusters in
      osteoarthritic cartilage.

PMID- 19748610
TI  - Speech intelligibility measured with shortened versions of Callsign Acquisition
      Test (CAT).
AB  - The Callsign Acquisition Test (CAT) is a new speech intelligibility test
      developed by the Human Research and Engineering Directorate of the U.S. Army
      Research Laboratory (ARL-HRED). CAT uses the phonetic alphabet and digit stimuli
      combined together to form 126 test items. OBJECTIVE: The purpose of this study
      was to assess the reliability of data collected with shorter versions of CAT.
      DESIGN: A total of 5 shorter versions of the original list (CAT-120, CAT-60, CAT
      40, CAT-30, and CAT-24) were formed and evaluated using 19 participants. Each of
      the subsets of CAT was presented in pink noise at signal-to-noise ratios (SNRs)
      of -6dB and -9dB. RESULTS: Results showed that shortened CAT lists have the
      capability of providing the same predictive power as the full CAT with good test
      retest reliability. CONCLUSIONS: Under the experimental conditions of this study,
      any of the shorter versions of the CAT can be utilized in place of the full
      version to reduce testing times with no effect on predictive power.

PMID- 19748611
TI  - ERCP by laparoscopic transgastric access and cholecystectomy at the same time in
      a patient with gastric bypass who was seen with choledocholithiasis.

PMID- 19748612
TI  - Endoscopic removal of dysfunctioning bands or rings after restrictive bariatric
      procedures.
AB  - BACKGROUND: Intragastric band migrations or dysfunctions are common long-term
      complications of both vertical banded gastroplasty (VBG) and laparoscopic
      adjustable gastric banding (Lap-Band) that classically require surgical
      treatment. OBJECTIVE: In this series, we describe the endoscopic removal of
      partially eroded Lap-Bands or Silastic rings and noneroded dysfunctioning rings
      after VBG. DESIGN: Case series. SETTING: A European, tertiary-care academic
      center. PATIENTS: This study involved 13 patients--3 with eroded Lap-Bands, 4
      with eroded Silastic rings, and 6 with refractory outlet stoma stenosis after
      VBG. INTERVENTION: Endoscopic removal was performed within 1 or 2 sessions,
      according to the presence and extent of band erosion at presentation, including
      optional placement of a self-expandable plastic stent across the band, followed
      about 6 to 8 weeks later by extraction with transsection, if needed, by using a
      wire-cutting system. MAIN OUTCOME MEASUREMENTS: Technical success and safety.
      RESULTS: One failure was caused by huge adhesion formation around a Lap-Band on
      the lesser curvature of the stomach and the left liver lobe. Twelve of 13
      endoscopic removals were successful in 1 (n = 2) and 2 (n = 10) sessions.
      LIMITATIONS: Highly selected patients (tertiary-case academic center).
      CONCLUSION: Endoscopic removal of dysfunctioning bands or rings is safe and
      feasible by the use of a 1- or 2-step endoscopic procedure.

PMID- 19748613
TI  - Gauze pledgetting versus endoscopic-guided aerosolized spray for nasal anesthesia
      before transnasal EGD: a prospective, randomized study.
AB  - BACKGROUND: Methods and efficacy of nasal anesthesia before ultrathin transnasal
      EGD (UT-EGD) are crucial for patient tolerance. OBJECTIVE: To compare patient
      tolerance, safety, and adverse events between cotton-tipped applicator primed
      gauze pledgetting (CTGP) and endoscopic-guided aerosolized spray (EGAS) methods
      of nasal anesthesia. DESIGN: We performed a prospective, randomized-controlled
      trial to compare procedural discomforts, optical quality, total procedure time,
      and adverse events between the CTGP and EGAS methods. SETTING: A large, tertiary
      referral hospital in Taiwan. PATIENTS: A total of 240 consecutive patients with
      epigastric discomfort were included in the study. INTERVENTION: The author
      performed all standardized nasal anesthesia and UT-EGD using a 5.9-mm diameter
      transnasal endoscope. MAIN OUTCOME MEASUREMENTS: Technical success, patient
      tolerability profiles, optical quality, total procedure time, and adverse events.
      RESULTS: There was no statistical difference in insertion failure rates between
      the 2 methods (CTGP 0% vs EGAS 5%, P = .07). When compared with the EGAS method,
      CTGP reduced pain during insertions through the inferior nasal meatus (3.4 +/-
      0.5 vs 3.2 +/- 0.4, P = .006), middle nasal meatus (4.0 +/- 0.7 vs 3.4 +/- 0.5, P
      = .002), and upper esophageal sphincter (2.9 +/- 0.7 vs 2.6 +/- 0.8, P = .005).
      CTGP elicited less unpleasant taste, fewer gagging episodes, and less throat pain
      after examination. Both methods had similar safe hemodynamic profiles, low
      epistaxis rates (0% vs 2%, P = .46), and comparable visual capacity and procedure
      time. Although similar proportions of patients in both groups would like to
      receive the same procedure the next time, CTGP had a higher overall tolerance.
      CONCLUSION: Compared with the EGAS method, CTGP achieved a better tolerability
      profile and elicited less bad taste, fewer gagging episodes, and less throat pain
      after UT-EGD in Taiwanese patients.

PMID- 19748614
TI  - Endoscopic diagnosis of a biliary neuroendocrine tumor.

PMID- 19748615
TI  - Large refractory colonic polyps: is it time to change our practice? A prospective
      study of the clinical and economic impact of a tertiary referral colonic mucosal
      resection and polypectomy service (with videos).
AB  - BACKGROUND: Patients who have large, difficult, colorectal lesions not readily
      amenable to endoscopic resection are often referred directly to surgery. The
      application of advanced polypectomy and endoscopic mucosal resection (EMR)
      techniques undertaken by a tertiary referral colonic mucosal resection and
      polypectomy service (TRCPS) is not often considered but may be superior to
      surgery. OBJECTIVE: To evaluate the safety, efficacy, and cost savings of a TRCPS
      for colorectal lesions. DESIGN: Prospective intention-to-treat analysis. SETTING:
      Tertiary academic referral center. PATIENTS: In a 21-month period ending in April
      2008, consecutive patients with large or complex colorectal polyps referred by
      other specialist endoscopists were prospectively enrolled on an intention-to
      treat basis. INTERVENTION: For sessile lesions, a standardized EMR approach was
      used. Pedunculated lesions were removed with or without pretreatment with an
      Endoloop procedure. MAIN OUTCOME MEASUREMENTS: Complete resection, complications,
      recurrence, and potential cost savings comparing actual outcome of the cohort
      with a hypothetical analysis of surgical management. RESULTS: This study included
      174 patients (mean age 68 years) who were referred with 193 difficult polyps (186
      laterally spreading, mean size 30 mm [range 10-80 mm]). We totally excised 173
      laterally spreading lesions by EMR (115 piecemeal, 58 en bloc). Invasive
      adenocarcinoma was found in 6 lesions-5 treated successfully with EMR. Eleven
      patients were referred directly to surgery without an endoscopic attempt due to
      suspected invasive carcinoma. Seven >30-mm, pedunculated polyps were removed.
      There were no perforations. A total of 20 bed days was used because of endoscopic
      complications. Among all patients referred, 90% avoided the need for surgery.
      Excluding patients who were treated surgically for invasive cancer, the
      procedural success was 95% (157 of 168). By using Australian cost estimates
      applied to the entire group and compared with cost estimates assuming all
      patients had undergone surgery, we calculated the total medical cost savings was
      $6990 (U.S.) per patient, or a total savings of $1,216,231 (U.S.). LIMITATION:
      Not a randomized trial. CONCLUSIONS: Colonoscopic polypectomy performed by a
      TRCPS on large or difficult polyps is technically effective and safe. This
      approach results in major cost savings and avoids the potential complications of
      colonic surgery. This type of clinical pathway should be developed to enhance
      patient outcomes and reduce health care costs.

PMID- 19748616
TI  - Age- and sex-specific yield of Barrett's esophagus by endoscopy indication.
AB  - BACKGROUND: Barrett's esophagus is a precursor of esophageal adenocarcinoma, both
      of which are associated with GERD. Screening GERD patients for Barrett's
      esophagus has been suggested, but it is not known which patients should be
      screened and at what age. OBJECTIVE: To determine the age-specific yield of
      endoscopy for Barrett's esophagus stratified by sex and indication for endoscopy.
      DESIGN: Retrospective cross-sectional study. SETTING: National Endoscopic
      Database of the Clinical Outcomes Research Initiative (CORI). PATIENTS: A total
      of 155,641 patients undergoing their first endoscopy at one of the CORI sites for
      clinical indications. MAIN OUTCOME MEASUREMENTS: Age-specific yield of Barrett's
      esophagus. RESULTS: Among white men with GERD, the yield of Barrett's esophagus
      increases steeply from early adulthood (2.1% in the third decade of life) to
      middle adulthood (9.3% in the sixth decade) and then plateaus (the difference for
      the eighth decade minus the sixth decade is -1.1%; 95% CI, -3.9% to 1.7%). There
      is no difference in the yield of Barrett's esophagus between middle-aged white
      women with GERD and white men without GERD (difference is -0.46%; 95% CI, -1.23%
      to 0.31%). LIMITATIONS: Possible bias by selection for endoscopy and the
      potential for misclassification of GERD status. CONCLUSIONS: The yield of upper
      endoscopy for the diagnosis of Barrett's esophagus increases rapidly among white
      men with GERD until approximately age 50 and then reaches a plateau. White women
      with GERD are at no increased risk compared with white men without GERD.

PMID- 19748617
TI  - Evaluating the effect of the new incentive system for high-risk pressure ulcer
      patients on wound healing and cost-effectiveness: a cohort study.
AB  - OBJECTIVE: To evaluate the effectiveness and cost-effectiveness of new incentive
      system for pressure ulcer management, which focused on skilled nurse staffing in
      terms of rate of healing and medical costs. DESIGN, SETTING AND PARTICIPANTS: A
      prospective cohort study included two types of groups: 39 institutions, which
      introduced the new incentive system, and 20 non-introduced groups (control).
      Sixty-seven patients suffering from severe pressure ulcers in the introduced
      group and 38 patients in the non-introduced group were included. Wound healing
      and medical costs were monitored weekly for three weeks by their skilled nurses
      in charge. MAIN OUTCOME MEASURES: Healing status and related medical costs.
      RESULTS: The introduced group showed significantly higher rate of healing
      compared with the control group at each weekly assessment. Multiple regression
      analysis revealed that the introduction of the new incentive system was
      independently associated with the faster healing rate (beta=3.44, P<.001). The
      budget impact analysis demonstrated that introducing this system could reduce
      cost of treating severe pressure ulcers by 1.776 billion yen per year.
      CONCLUSIONS: The new incentive system for the management of pressure ulcers,
      which focused on staffing with skilled nurses can improve healing rate with
      reduced medical cost.

PMID- 19748618
TI  - Association of low glomerular filtration rate and albuminuria with peripheral
      arterial disease: the National Health and Nutrition Examination Survey, 1999
      2004.
AB  - Microalbuminuria may be an early sign of intra-renal vascular dysfunction and a
      marker of vascular risk in the general population as well as in high-risk
      individuals. However, the association between albuminuria and PAD has been
      demonstrated only in few small studies. The aim of current study is to evaluate
      the relative impact of albuminuria and glomerular filtration rate on the risk of
      peripheral artery disease (PAD) in a nationally representative sample population.
      Data (ankle brachial index [ABI], urine albumin, fasting glucose, and glomerular
      filtration rate [GFR] estimated using the Modification of Diet in Renal Disease
      [MDRD] Study equation) were collected on 7068 adults from the National Health and
      Nutrition Examination Survey (NHANES 1999-2004). PAD was defined as ABI <0.9 or
      >1.4. There was a trend towards an association between the presence of abnormal
      renal function (GFR<60mL/min/1.73m(2)) and PAD in the non-diabetic patients (OR
      of 1.43, 95% CI: 0.98-2.09; P=0.07) where as the presence of abnormal renal
      function was strongly associated PAD in the diabetic patients (OR of 2.3, 95% CI:
      1.34-3.95; P=0.046). On the contrary, albuminuria was independently associated
      with PAD in the non-diabetic (OR, 1.87; 95% CI, 1.38-2.52; P=0.0003) but not in
      the diabetic patients (OR: 1.08, 95% CI: 0.68-1.73, P=0.7411). We concluded that
      albuminuria, independent of renal function, is strongly associated with PAD in
      non-diabetic subjects. As diabetes develops and HbA1c level increases, the
      predictive value of albuminuria gradually diminishes after adjustment for renal
      function.

PMID- 19748619
TI  - Contribution of apolipoprotein E genotype and docosahexaenoic acid to the LDL
      cholesterol response to fish oil.
AB  - OBJECTIVES: To investigate the impact of apolipoprotein E (apoE) genotype on the
      response of the plasma lipoprotein profile to eicosapentaenoic acid (EPA) versus
      docosahexaenoic acid (DHA) intervention in humans. METHODS AND RESULTS: 38
      healthy normolipidaemic males, prospectively recruited on the basis of apoE
      genotype (n=20 E3/E3 and n=18 E3/E4), completed a double-blind placebo-controlled
      cross-over trial, consisting of 3 x 4 week intervention arms of either control
      oil, EPA-rich oil (ERO, 3.3g EPA/day) or DHA-rich oil (DRO, 3.7g DHA/day) in
      random order, separated by 10 week wash-out periods. A significant genotype
      independent 28% and 19% reduction in plasma triglycerides in response to ERO and
      DRO was observed. For total cholesterol (TC), no significant treatment effects
      were evident; however a significant genotype by treatment interaction emerged
      (P=0.045), with a differential response to ERO and DRO in E4 carriers. Although
      the genotype x treatment interaction for LDL-cholesterol (P=0.089) did not reach
      significance, within DRO treatment analysis indicated a 10% increase in LDL
      (P=0.029) in E4 carriers with a non-significant 4% reduction in E3/E3
      individuals. A genotype-independent increase in LDL mass was observed following
      DRO intervention (P=0.018). Competitive uptake studies in HepG2 cells using
      plasma very low density lipoproteins (VLDL) from the human trial, indicated that
      following DRO treatment, VLDL(2) fractions obtained from E3/E4 individuals
      resulted in a significant 32% (P=0.002) reduction in LDL uptake relative to the
      control. CONCLUSIONS: High dose DHA supplementation is associated with increases
      in total cholesterol in E4 carriers, which appears to be due to an increase in
      LDL-C and may in part negate the cardioprotective action of DHA in this
      population subgroup.

PMID- 19748620
TI  - Impact of implanted bone marrow progenitor cell composition on limb salvage after
      cell implantation in patients with critical limb ischemia.
AB  - OBJECTIVE: The aim of this study is to identify which factors influence limb
      salvage after bone marrow mononuclear cell implantation (BMI) in patients with
      chronic critical limb ischemia (CLI). METHODS: Thirteen no-option CLI patients
      treated with BMI were enrolled in the present study. Limb ischemia was assessed
      using the ankle-brachial index (ABI), transcutaneous oxygen tension (TcO(2)), and
      rest pain score. The cell populations among the implanted cells were determined
      by May-Giemsa staining and flow cytometry. RESULTS: Major lower extremity
      amputations after BMI were performed in seven patients. Before implantation,
      there were no significant differences between the amputation group (n=7) and the
      salvage group (n=6) in clinical characteristics, the ABI, the TcO(2) level, or
      the rest pain score. After implantation, there were no differences between the
      groups in the serum levels of angiogenic or inflammatory cytokines. The number of
      implanted BM cells was the same in the two groups, but the cells implanted in the
      limb salvage group were composed of significantly higher numbers of hematopoietic
      progenitors (erythroblasts and myeloblasts) and lymphocytes (p<0.05,
      respectively). The number of CD34-positive cells was somewhat greater in the
      salvage group than in the amputation group (p=0.09) and was positively associated
      with the number of erythroblasts (r(2)=0.29, p=0.06) and the number of
      myeloblasts (r(2)=0.59, p<0.01). CONCLUSIONS: The cellular composition of the BM
      cells injected may affect limb salvage after the implantation in patients with
      severe CLI. The favorable effects of BMI appear to reflect the impact of the
      progenitor cell doses.

PMID- 19748621
TI  - Factors predicting cardiovascular events in statin-treated diabetic and non
      diabetic patients with coronary atherosclerosis.
AB  - OBJECTIVE: We aimed at identifying which lipid factors drive vascular risk in
      statin-treated patients with coronary artery disease (CAD). METHODS: We recorded
      vascular events over 5.6 years in 491 consecutive statin-treated patients with
      angiographically proven stable CAD, covering 2750 patient-years. RESULTS: In the
      total population, low high-density lipoprotein (HDL) cholesterol (standardized
      adjusted HR 0.73 [0.60-0.89]; p=0.001), low apolipoprotein A1 (0.77 [0.65-0.92];
      p=0.003), a small low-density lipoprotein (LDL) particle diameter (0.76 [0.64
      0.91]; p=0.002), and high triglycerides (1.20 [1.05-1.38]; p=0.007) predicted
      vascular events, but not total cholesterol, LDL cholesterol, or apolipoprotein B.
      Factor analysis in the lipid profiles of our patients revealed an HDL-related
      factor and an LDL-related factor. Concordant with the results for individual
      lipid parameters, the HDL-related factor (0.69 [0.58-0.83]; p<0.001) but not the
      LDL-related factor (p=0.455) predicted vascular events. Patients with type 2
      diabetes (T2DM; n=116) were at a higher vascular risk than non-diabetic subjects
      (38.6% vs. 24.1%; p<0.001), and like in the total population the HDL-related
      factor (0.59 [0.44-0.77]; p<0.001) but not the LDL-related factor (p=0.591)
      predicted vascular risk in diabetic patients. CONCLUSIONS: The pattern of low HDL
      cholesterol, low apolipoprotein A1, small LDL particles, and high triglycerides
      drives vascular risk in statin-treated coronary patients, particularly in those
      with T2DM.

PMID- 19748622
TI  - ADRP/ADFP and Mal1 expression are increased in macrophages treated with TLR
      agonists.
AB  - Activation of macrophages by TLR agonists enhances foam cell formation, but the
      underlying mechanisms are not understood. We examined the effects of TLR agonists
      on ADRP/ADFP, a protein associated with forming lipid droplets, and Mal1 a fatty
      acid-binding protein, in two mouse macrophage cell lines and human monocytes. Low
      doses of LPS, a TLR4 agonist increased both mRNA and protein levels of ADRP/ADFP
      and Mal1 in RAW 264.7 macrophages. Following pretreatment with Intralipid, fatty
      acids, or acetyl-LDL to increase triglyceride or cholesterol ester storage, LPS
      treatment still increased ADRP/ADFP and Mal1 mRNA levels. LPS also induced
      ADRP/ADFP and Mal1 in J774 macrophages and ADRP/ADFP in human monocytes. Zymosan,
      a fungal product that activates TLR2, poly-I:C, a viral mimetic that activates
      TLR3, and imiquimod, a TLR7 agonist, also increased ADRP/ADFP. Zymosan, but not
      poly-I:C or imiquimod, induced Mal1. In contrast, neither gene was induced by
      TNFalpha, IL-1beta, IL-6, or interferon-gamma. Thus TLR agonists induce ADRP/ADFP
      and Mal1, which likely contributes to macrophage triglyceride and cholesterol
      ester storage leading to foam cell formation.

PMID- 19748623
TI  - Computer-aided non-contrast CT-based quantification of pericardial and thoracic
      fat and their associations with coronary calcium and Metabolic Syndrome.
AB  - INTRODUCTION: Pericardial fat is emerging as an important parameter for
      cardiovascular risk stratification. We extended previously developed quantitation
      of thoracic fat volume (TFV) from non-contrast coronary calcium (CC) CT scans to
      also quantify pericardial fat volume (PFV) and investigated the associations of
      PFV and TFV with CC and the Metabolic Syndrome (METS). METHODS: TFV is quantified
      automatically from user-defined range of CT slices covering the heart.
      Pericardial fat contours are generated by spline interpolation between 5-7
      control points, placed manually on the pericardium within this cardiac range.
      Contiguous fat voxels within the pericardium are identified as pericardial fat.
      PFV and TFV were measured from non-contrast CT for 201 patients. In 105 patients,
      abdominal visceral fat area (VFA) was measured from an additional single-slice
      CT. In 26 patients, images were quantified by two readers to establish inter
      observer variability. TFV and PFV were examined in relation to Body Mass Index
      (BMI), waist circumference and VFA, standard coronary risk factors (RF), CC
      (Agatston score >0) and METS. RESULTS: PFV and TFV showed excellent correlation
      with VFA (R=0.79, R=0.89, p<0.0001), and moderate correlation with BMI (R=0.49,
      R=0.48, p<0.0001). In 26 scans, the inter-observer variability was greater for
      PFV (8.0+/-5.3%) than for TFV (4.4+/-3.9%, p=0.001). PFV and TFV, but not RF,
      were associated with CC [PFV: p=0.04, Odds Ratio 3.1; TFV: p<0.001, OR 7.9]. PFV
      and TFV were also associated with METS [PFV: p<0.001, OR 6.1; TFV p<0.001, OR
      5.7], unlike CC [OR=1.0 p=NS] or RF. PFV correlated with low-HDL and high
      glucose; TFV correlated with low-HDL, low-adiponectin, and high glucose and
      triglyceride levels. CONCLUSIONS: PFV and TFV can be obtained easily and
      reproducibly from routine CC scoring scans, and may be important for risk
      stratification and monitoring.

PMID- 19748624
TI  - Novel approach to ambulatory assessment of human segmental orientation on a
      wearable sensor system.
AB  - A new method using a double-sensor difference based algorithm for analyzing human
      segment rotational angles in two directions for segmental orientation analysis in
      the three-dimensional (3D) space was presented. A wearable sensor system based
      only on triaxial accelerometers was developed to obtain the pitch and yaw angles
      of thigh segment with an accelerometer approximating translational acceleration
      of the hip joint and two accelerometers measuring the actual accelerations on the
      thigh. To evaluate the method, the system was first tested on a 2 degrees of
      freedom mechanical arm assembled out of rigid segments and encoders. Then, to
      estimate the human segmental orientation, the wearable sensor system was tested
      on the thighs of eight volunteer subjects, who walked in a straight forward line
      in the work space of an optical motion analysis system at three self-selected
      speeds: slow, normal and fast. In the experiment, the subject was assumed to walk
      in a straight forward way with very little trunk sway, skin artifacts and no
      significant internal/external rotation of the leg. The root mean square (RMS)
      errors of the thigh segment orientation measurement were between 2.4 degrees and
      4.9 degrees during normal gait that had a 45 degrees flexion/extension range of
      motion. Measurement error was observed to increase with increasing walking speed
      probably because of the result of increased trunk sway, axial rotation and skin
      artifacts. The results show that, without integration and switching between
      different sensors, using only one kind of sensor, the wearable sensor system is
      suitable for ambulatory analysis of normal gait orientation of thigh and shank in
      two directions of the segment-fixed local coordinate system in 3D space. It can
      then be applied to assess spatio-temporal gait parameters and monitoring the gait
      function of patients in clinical settings.

PMID- 19748625
TI  - The problem of measurement indeterminacy in complex neurobiological movement
      systems.
AB  - In the study of complex neurobiological movement systems, measurement
      indeterminacy has typically been overcome by imposing artificial modelling
      constraints to reduce the number of unknowns (e.g., reducing all muscle, bone and
      ligament forces crossing a joint to a single vector). However, this approach
      prevents human movement scientists from investigating more fully the role,
      functionality and ubiquity of coordinative structures or functional motor
      synergies. Advancements in measurement methods and analysis techniques are
      required if the contribution of individual component parts or degrees of freedom
      of these task-specific structural units is to be established, thereby effectively
      solving the indeterminacy problem by reducing the number of unknowns. A further
      benefit of establishing more of the unknowns is that human movement scientists
      will be able to gain greater insight into ubiquitous processes of physical self
      organising that underpin the formation of coordinative structures and the
      confluence of organismic, environmental and task constraints that determine the
      exact morphology of these special-purpose devices.

PMID- 19748626
TI  - In-vivo three-dimensional carpal bone kinematics during flexion-extension and
      radio-ulnar deviation of the wrist: Dynamic motion versus step-wise static wrist
      positions.
AB  - An in-vivo approach to the measurement of three-dimensional motion patterns of
      carpal bones in the wrist may have future diagnostic applications, particularly
      for ligament injuries of the wrist. Static methods to measure carpal kinematics
      in-vivo only provide an approximation of the true kinematics of the carpal bones.
      This study is aimed at finding the difference between dynamically and statically
      acquired carpal kinematics. For eight healthy subjects, static and a dynamic
      measurements of the carpal kinematics were performed for a flexion-extension and
      a radio-ulnar deviation movement. Dynamic scans were acquired by using a four
      dimensional X-ray imaging system during an imposed cyclic motion. To assess
      static kinematics of the wrists, three-dimensional rotational X-ray scans were
      acquired during step-wise flexion-extension and radio-ulnar deviation. The
      helical axis rotations and the rotation components. i.e. flexion-extension, radio
      ulnar deviation and pro-supination were the primary parameters. Linear mixed
      model statistical analysis was used to determine the significance of the
      difference between the dynamically and statically acquired rotations of the
      carpal bones. Small and in most cases negligible differences were observed
      between the dynamic motion and the step-wise static motion of the carpal bones.
      The conclusion is that in the case of individuals without any pathology of the
      wrist, carpal kinematics can be studied either dynamically or statically. Further
      research is required to investigate the dynamic in-vivo carpal kinematics in
      patients with dynamic wrist problems.

PMID- 19748627
TI  - Nanotribological characterization of tooth enamel rod affected by surface
      treatment.
AB  - Tooth enamel is a hybrid organic-inorganic bionanocomposite comprised
      predominantly of enamel rods. Understanding the effects of anti-caries treatment
      on the biomechanical properties of these rods is essential in developing
      effective caries prevention strategies. Calcium fluoride-like deposits play an
      important role in caries prevention and their nanotribological properties have a
      direct effect upon their long-term effectiveness. Accordingly, this study
      utilizes a variety of techniques, namely nanoindentation, nanoscratch tests,
      nanowear tests and atomic force microscopy (AFM), to characterize the mechanical
      and tribological properties of single enamel rods before and after topical
      fluoride application. The results show that the CaF(2)-like deposits formed on
      the enamel surface following fluoride application increase the coefficient of
      friction of the enamel rods, but decrease their critical load and nanohardness.
      As a result, the nanowear depth of the treated enamel surface is around six times
      higher than that of the native enamel surface under an applied load of 300
      microN. Following the removal of the surface deposits, however, the modulus of
      elasticity and wear depth of the underlying enamel surface are found to be
      similar to those of the original enamel surface. However, a notable increase in
      the surface roughness is observed.

PMID- 19748628
TI  - Evidence of 13C non-covalent isotope effects obtained by quantitative 13C nuclear
      magnetic resonance spectroscopy at natural abundance during normal phase liquid
      chromatography.
AB  - Quantitative isotopic (13)C NMR at natural abundance has been used to determine
      the site-by-site (13)C/(12)C ratios in vanillin and a number of related compounds
      eluted from silica gel chromatography columns under similar conditions. Head-to
      tail isotope fractionation is observed in all compounds at the majority of carbon
      positions. Furthermore, the site-specific isotope deviations show signatures
      characteristic of the position and functionality of the substituents present. The
      observed effects are more complex than would be obtained by simply summing the
      individual effects. Such detail is hidden when only the global (13)C content is
      measured by mass spectrometry. In particular, carbon positions within the
      aromatic ring are found to show site-specific isotope fractionation between the
      solute and the stationary phase. These interactions, defined as non-covalent
      isotope effects, can be normal or inverse and vary with the substitution pattern
      present.

PMID- 19748629
TI  - Friedreich's ataxia: oxidative stress and cytoskeletal abnormalities.
AB  - Friedreich's ataxia (FRDA) is an autosomal recessive disorder caused by mutations
      in the gene encoding frataxin, a mitochondrial protein implicated in iron
      metabolism. Current evidence suggests that loss of frataxin causes iron overload
      in tissues, and increase in free-radical production leading to oxidation and
      inactivation of mitochondrial respiratory chain enzymes, particularly Complexes
      I, II, III and aconitase. Glutathione plays an important role in the
      detoxification of ROS in the Central Nervous System (CNS), where it also provides
      regulation of protein function by glutathionylation. The cytoskeletal proteins
      are particularly susceptible to oxidation and appear constitutively
      glutathionylated in the human CNS. Previously, we showed loss of cytoskeletal
      organization in fibroblasts of patients with FRDA found to be associated with
      increased levels of glutathione bound to cytoskeletal proteins. In this study, we
      analysed the glutathionylation of proteins in the spinal cord of patients with
      FRDA and the distribution of tubulin and neurofilaments in the same area. We
      found, for the first time, a significant rise of the dynamic pool of tubulin as
      well as abnormal distribution of the phosphorylated forms of human neurofilaments
      in FRDA motor neurons. In the same cells, the cytoskeletal abnormalities co
      localized with an increase in protein glutathionylation and the mitochondrial
      proteins were normally expressed by immunocytochemistry. Our results suggest that
      in FRDA oxidative stress causes abnormally increased protein glutathionylation
      leading to prominent abnormalities of the neuronal cytoskeleton.

PMID- 19748630
TI  - Safety and durability of mitral valve repair for anterior leaflet perforation.
AB  - OBJECTIVE: We sought to evaluate mitral valve repair for anterior leaflet
      perforation. METHODS: Between October 1987 and October 2006, 26 patients with
      mitral valve anterior leaflet perforation underwent mitral valve repair (median
      age, 54 years; 18 [69%] were male). RESULTS: The indication for operation was
      severe mitral regurgitation only in 14 patients, both aortic regurgitation and
      mitral regurgitation in 11, and ventricular septal defect repair in 1. Twenty
      four (92%) patients had endocarditis and 13 (50%) had at least mild aortic
      regurgitation preoperatively. Left atriotomy was performed in 17 (65%) and
      aortotomy in 8 (31%). Six (23%) patients had visible vegetations at the time of
      repair. For anterior leaflet repair, a patch was used in 11 (42%) patients and
      primary suture closure in 15 (58%). Eighteen patients underwent concomitant
      cardiac surgical procedures. Postoperative follow-up (mean, 6 years) was
      available for 25 (96%) patients. There was 1 early death from multiorgan failure
      and 2 late deaths. Patient survival was 95% at 1 year and 90% at 5 years. Left
      ventricular end-diastolic dimension improved significantly after mitral valve
      repair at dismissal (n = 16; -9.4 mm; P < .01) and during follow-up (n = 11; 
      10.8 mm; P < .01). Only 1 (4%) patient had mitral valve reoperation after 7 years
      owing to recurrent endocarditis 6 months after repair. CONCLUSIONS: Mitral valve
      anterior leaflet perforation may be safely repaired with good midterm survival
      and durability.

PMID- 19748631
TI  - Impaired angiogenic potency of bone marrow cells from patients with advanced age,
      anemia, and renal failure.
AB  - OBJECTIVE: The implantation of autologous bone marrow-derived cells has been used
      for the treatment of ischemic diseases, but obvious interindividual differences
      were observed in the improvement of regional perfusion and cardiac function after
      treatment. We examined the angiogenic potency of bone marrow cells from patients
      with different clinical backgrounds. METHODS: Bone marrow cells were collected
      from 25 patients scheduled to undergo sternotomy for various surgical procedures.
      We examined the quality of bone marrow cells and investigated their angiogenic
      potency by using an ischemic limb model in mice with severe combined
      immunodeficiency. RESULTS: When compared with their control cohort, bone marrow
      cells from patients with advanced age, renal failure, or anemia had significantly
      less c-kit- and CD34-positive stem cells (P < .05) and showed significantly lower
      vascular endothelial growth factor production and colony-forming units in culture
      (P < .05). Furthermore, the implantation of bone marrow cells from patients with
      advanced age, renal failure, or anemia into the ischemic limbs of mice also
      resulted in significantly worse blood flow recovery and clinical score when
      compared with the implantation of bone marrow cells from their control cohorts (P
      < .05). However, the bone marrow cells from patients with diabetes and
      hypertension did not show significant impairment of angiogenic potency when
      compared with their control cohorts. CONCLUSIONS: The quality and angiogenic
      potency of bone marrow cells differs among patients. Advanced age, renal failure,
      and anemia should be the risk factors related to poor angiogenic potency of bone
      marrow cells for the treatment of ischemic diseases.

PMID- 19748632
TI  - Migration forces of transcatheter aortic valves in patients with noncalcific
      aortic insufficiency.
AB  - OBJECTIVE: Transcatheter aortic valves have been successfully implanted into the
      calcified leaflets of patients with severe aortic stenosis. However, their
      stability in patients with noncalcified aortic insufficiency is unknown. Similar
      to thoracic and abdominal aortic stent grafts, transcatheter aortic valves are
      subjected to antegrade ejection forces during systole. However, retrograde
      migration forces into the left ventricle are also generated by the diastolic
      pressure gradient across the closed valve. It has been suggested that leaflet
      calcification anchors the prosthesis, and measurements of migration forces should
      be considered before clinical trials in noncalcified aortic insufficiency. The
      objective of this study was to use computational fluid dynamics simulations to
      quantify forces that could potentially dislodge the prosthesis. METHODS: A
      computational fluid dynamics model was developed to simulate systolic flow
      through a geometric mesh of the aortic root and transcatheter aortic valves.
      Hemodynamic measurements were made at discrete moments during ejection. Unsteady
      control volume analysis was used for calculations of force on the mesh. RESULTS:
      Results of the simulation indicate that a total force of 0.602 N acts on the
      transcatheter aortic valves during systole, 99% of which is in the direction of
      axial flow. The largest contributor to force was the dynamic pressure gradient
      through the transcatheter aortic valves. This antegrade force is approximately 10
      times smaller than the retrograde force (6.01 N) on the closed valve during
      diastole. CONCLUSION: Our model simulated systolic flow through a transcatheter
      aortic valve and demonstrated migration into the left ventricle to be of greater
      concern than antegrade ejection.

PMID- 19748633
TI  - [Effectiveness of population-based interventions on the prevention of overweight
      in children and adolescents].
AB  - This study aimed to assess the available scientific evidence on the effectiveness
      or cost-effectiveness of interventions to prevent obesity, carried out in child
      and adolescent population. We conducted a systematic review, searching 10
      databases and other resource directories for the period January 1998-July 2008.
      We assessed study quality and extracted and summarized information that met the
      established criteria. Results included 40 studies that evaluated interventions
      showing mostly components of physical activity, nutrition and education. We found
      no evaluations of cost-effectiveness. Thirteen studies resulted in a significant
      reduction in favor of intervention in some of the anthropometric measurements. In
      conclusion, some interventions showed an impact in preventing weight gain.
      However, it is weak, since most studies have not had the expected result, were
      heterogeneous and of short duration.

PMID- 19748634
TI  - [Prognostic prediction in patients with hepatocellular carcinoma not amenable to
      locoregional treatment].
AB  - BACKGROUND AND OBJECTIVE: Patients with hepatocellular carcinoma (HCC) not
      amenable to locoregional therapy have some specific clinical characteristics
      (advanced cirrhosis or extrahepatic spread) that lead us to ascertain the
      prognostic efficacy of the different staging systems proposed for this entity.
      PATIENTS AND METHOD: We analyze 100 patients (69 males) with a mean age of 70.2
      (10.7) years. Tumor staging was performed at baseline according to the following
      systems: Okuda, Cancer of the Liver Italian Program (CLIP), Barcelona Clinic
      Liver Cancer (BCLC), and Japan Integrated Staging (JIS) score. We determine the
      area under the receiver operating characteristic curve (AUC) using the 6 and 12
      month mortality as endpoint. RESULTS: The BCLC system had the best predictive
      power for mortality both at 6 (AUC, 0.871) and 12 months (AUC, 0.924) from
      diagnosis. In the Cox multivariate analysis, this model showed an independent
      prognostic effect [hazard ratio: 9.14 for BCLC stage C versus A (p<0.001), and
      9.53 for stage D versus A (p=0.004)]. CONCLUSIONS: The BCLC system provided the
      best prognostic stratification for patients with HCC not amenable to locoregional
      therapy.

PMID- 19748635
TI  - [Learning from in-hospital mortality in internal medicine].

PMID- 19748636
TI  - [Significance of anemia as an independent prognostic factor in patients with
      renal cell carcinoma].
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to analyze the significance
      of anemia as well as other prognostic factors influencing survival in patients
      with renal cell carcinoma (RCC). PATIENTS AND METHODS: A retrospective review of
      data of 316 patients who underwent surgery between 1970 and 2003 was performed.
      Most important known prognostic factors of RCC were investigated. RESULTS: Most
      of patients had T1b-T2, low nuclear grade and single tumours. In 8.2% and 9% of
      cases, lymph node and metastatic dissemination were detected at the time of
      diagnosis, respectively. At the beginning, most frequent symptoms were hematuria
      and pain, with anemia (Hb >10g/dl) in 69 patients. After a median follow-up of 50
      months, 24.1% of patients had a recurrence. From these, more than 50% developed
      recurrence within one year after nephrectomy. Advanced tumours (T3-4) consisted
      of high nuclear grade (III-IV) tumours, larger size tumours, with necrosis and
      vascular infiltration in surgical specimen, as well as lymph node and metastatic
      dissemination. In multivariate analysis, anemia, time to recurrence, type of
      treatment for recurrence as well as lymph node dissemination were independent
      factors of cancer specific survival. CONCLUSION: Anemia seems to be a marker of
      recurrence and progression in patients with renal cell carcinoma undergoing
      nephrectomy. From our point of view, anemia could be considered a significantly
      high mortality rate for renal cancer in these patients.

PMID- 19748637
TI  - [C-reactive protein and carotid intima-media thickness in atherothrombotic
      ischemic stroke].
AB  - BACKGROUND AND OBJECTIVE: We aimed to investigate the relation between values of
      C-reactive protein (CRP) and carotid artery intima-media thickness (IMT) in
      patients with atherothrombotic ischemic stroke. PATIENTS AND METHOD: One hundred
      and thirty five patients within 48h after index ischemic stroke were included.
      CRP levels were obtained at this time and a carotid ultrasonography was
      performed. Neurological and functional disability were evaluated, and all
      patients underwent a cardiovascular risk stratification. Patients were divided in
      three groups according to the tertiles of they IMT distribution. We adjusted for
      the possible confounding effect using a multivariate logistic model. RESULTS:
      Forty three in-patients were classified into group 1 (IMT between 0.7 and 1.1
      millimetres), 43 into group 2 (IMT between 1.2 and 1.5 millimetres) and 49 into
      group 3 (IMT higher of 1.6 millimetres). We found a significant elevation of CRP
      levels at different groups (p<0.0008), with medians by group of 0.3, 0.4 and
      1.5mg/dl respectively. Likewise, we found significant differences by group in
      functional disability (p<0.03) and in vascular risk stratification (p<0.02).
      CONCLUSIONS: CRP is a marker of increased IMT in patients with atherothrombotic
      ischemic stroke. A cutoff point of 1.5mg/dl for CRP provided a greater IMT and a
      worse outcome in functional disability as cardiovascular risk. Therefore, this
      group requires a more intensive treatment in secondary prevention.

PMID- 19748638
TI  - [Prader Willi syndrome patients: study of 77 patients].
AB  - BACKGROUND: The Prader-Willi syndrome (PWS) is a disease of genetic origin. It is
      characterized by neonatal hypotonia, hypogonadism, hiperfagia leading to obesity,
      low stature, developmental delay, moderate mental retardation, abnormal behavior
      and characteristic facial appearance. It is caused by the loss or the
      inactivation of paternal genes of the imprinted region 15q11-13. There are
      different genetic causes: paternal 15q11-q13 deletion in 70% of patients,
      maternal uniparental disomy in the 20-25% and less than 5% have an imprinting
      defect. We present the results obtained in the transverse clinical - genetic
      study of 77 PWS patients. PATIENTS AND METHODS: There has been realized the study
      of 374 suspected PWS patients. Cytogenetics studies of bands G and hybridization
      in situ fluorescent (FISH) and molecular genetics analysis of microsatellites,
      Southern blot, MS-PCR and sequenciation were carried out. Holm's criteria use for
      the correlation phenotype - genotype in 48 patients. RESULTS: PWS was confirmed
      in 77 patients, 46 deletion, 16 uniparental disomy, two imprinting defect and 13
      only PWS methylation pattern. Significant differences do not observe in the
      correlation phenotype - genotype. CONCLUSIONS: The frequencies of the molecular
      alterations, 71.87 % deletion, 25 % UPD and 3.12 % DI, they are similar to
      described in the literature. It presents the algorithm of diagnosis used with the
      MS-PCR as rapid technology to confirm PWS.

PMID- 19748639
TI  - [Staphylococcus aureus with diminished sensitivity to vancomycin. New problems
      for the clinician].

PMID- 19748640
TI  - [Diagnostic biomarkers of malignant pleural mesothelioma].

PMID- 19748641
TI  - [An ambulatory physical exercise program improves in the short term weight and
      quality of life of obese post-menopausal women].
AB  - OBJECTIVES: To evaluate the effects of an ambulatory physical exercise program on
      the quality of life, anthropometric and biochemical parameters in obese post
      menopausal women. METHODS: One hundred and six obese post-menopausal women were
      randomized to take part in an ambulatory program of physical exercise (aerobic
      and anaerobic), or to receive conventional information about diet and exercise.
      After three months, effects on quality of life were evaluated (test Euroqol,
      Rosenberg and subjective evaluation of health), weight, BMI, waist perimeter and
      fat mass, and biochemical parameters. RESULTS: Mean age was 59.79 (8.02) years
      and BMI 37.51 (6.03) kg/m(2). Women included in the exercise group improved their
      quality of life after three months (EuroQol 0.48 (0.38) vs 0.66 (0.35);
      Rosenberg: 19.21 (5.05) vs 16.86 (4.94); subjective evaluation of health (%):
      60.68 (19.99) vs 71.14 (17.28); p<0.01) and lost weight (90.95 (15.51) vs 88.72
      (15.17); p<0.001), BMI (37.5 (5.68) vs 36.59 (5.72); p<0.001) and fat mass (46.28
      (4.92)% vs 45.47 (4.88)%; p<0.01). No changes were observed in control group. 31
      people withdrew the study before 12 weeks. CONCLUSIONS: An ambulatory physical
      exercise program improves quality of life and reduces weight and fat mass, in a
      short period of time, in obese post-menopausal women. The high rate of withdrawal
      should be considered as an inconvenient in this type of programs.

PMID- 19748642
TI  - [The pudendal nerve: clinical and therapeutic morphogenesis, anatomy, and
      physiopathology].
AB  - The pudendal is the king of the perineum. Most often originating in the S3 root,
      it is responsible for the teguments of the perineum (glans penis, clitoris,
      scrotum, and the labia majora, the skin of the central fibrous perineal body,
      anus), but also the erector muscles and the striated sphincters. The social
      nerve, it controls erection and the voluntary sphincters. It is also the nerve of
      the beginnings of sexual sensation and masturbation. Its injury is expressed in
      perineal pain, which, when positional, suggests a tunnel syndrome. The
      compression points have become well known: ligament pinching between the
      sacrotuberous and sacrospinous ligaments, the falciform process and the pudendal
      canal (Alcock canal). The data from questioning the patient, the results of the
      neurological exam, and the at least momentary response to infiltration define the
      Nantes criteria, which confirm the diagnosis. Treatment is medical, physical
      therapy, infiltration, and, as a last resort, surgery. The results have improved
      because of new technical norms, with 75% of operated patients benefiting from
      surgery. This disorder has become well known and should be remembered, thus
      sparing the patient from years of suffering and needless consultations for
      patients who do not present with organ disease, too often implicated instead of a
      true canal neuropathy, whose clinical manifestation and treatment have now been
      validated.

PMID- 19748643
TI  - Prevalence and time trends in diabetes and physical inactivity among adult West
      African populations: the epidemic has arrived.
AB  - OBJECTIVE: To determine the prevalence and distribution of, and trends in,
      physical inactivity and diabetes in adult West African populations. DESIGN:
      Systematic review and meta-analysis. METHODS: Literature searches were conducted
      using four electronic databases. Journal hand searches and examination of
      citations of relevant articles were also undertaken. To be included, studies had
      to be population based, use clearly defined criteria for measuring diabetes and
      physical inactivity, present data that allowed calculation of the prevalence of
      diabetes or physical inactivity, and sample adult participants. Studies retrieved
      were appraised critically. Meta-analysis was performed using the DerSimonian
      Laird random effect model. RESULTS: Twenty-one reports were retrieved for
      diabetes and 15 reports were retrieved for physical in/activity. Most studies (10
      for diabetes and six for physical activity) were conducted solely among urban
      populations. The prevalence of diabetes in West Africa was approximately 4.0%
      [95% confidence interval (CI) 2.0-9.0] in urban adults and 2.6% (95%CI 1.5-4.4)
      in rural adults, and was similar in men and women [prevalence ratio (PR) 1.36,
      95%CI 0.96-1.92]. Cumulative time trend analyses suggested an increase in the
      prevalence of diabetes among adults in urban West Africa, from approximately 3.0%
      (95%CI 1.0-7.0) to 4.0% (95%CI 2.0-9.0) in the past 10 years. The prevalence of
      inactivity in West Africa was 13% (95%CI 9.0-18.0). An association was found
      between physical inactivity and being older (> or = 50 years) (PR 1.82, 95%CI
      1.36-2.44), female gender (PR 1.62, 95%CI 1.41-1.87) and urban residence (PR
      2.04, 95%CI 1.58-2.63). CONCLUSIONS: Diabetes and physical inactivity are
      important public health issues in urban West Africa, with similar prevalences to
      wealthy industrialized countries. There is an urgent need for policy makers,
      politicians and health promotion experts to put measures in place to encourage
      active lifestyles and control diabetes in urban West Africa.

PMID- 19748644
TI  - Guidelines for the development of social marketing programmes for sun protection
      among adolescents and young adults.
AB  - OBJECTIVES: To formulate 'best practice' guidelines for social marketing
      programmes for adolescents' and young adults' sun protection. STUDY DESIGN: A
      Delphi consensus process. METHODS: Eleven experts in sun protection and social
      marketing participated in a Delphi consensus process, where they were asked to
      provide up to 10 key points, based on their knowledge and practical experience,
      which they felt were most important in developing social marketing interventions
      for the primary prevention of skin cancer among adolescents and young adults.
      After reaching consensus, the evidence base for each guideline was determined and
      graded via the Scottish Intercollegiate Guideline Network grading system.
      Participants were then asked to indicate how strongly they rated the finalized 15
      recommendations based on all aspects relating to their knowledge and practical
      opinion, as well as the research evidence, on a visual analogue scale. RESULTS:
      The resultant 15 guidelines offer general principles for sun protection
      interventions utilizing a social marketing approach. CONCLUSIONS: This method of
      guideline development brought the expertise of practitioners to the forefront of
      guideline development, whilst still utilizing established methods of evidence
      confirmation. It thus offers a useful method for guideline development in a
      public health context.

PMID- 19748645
TI  - Loss of p27 expression in canine mammary tumors and their metastases.
AB  - The p27 gene is a member of the cyclin-dependent kinase inhibitors, which arrest
      G1- to S-phase transition of the cell cycle. We have previously shown a
      significant reduction of p27 mRNA expression level in laser-microdissected
      mammary carcinomas and their lymph node metastases when compared to non
      neoplastic mammary gland of the same dog. Here, p27 expression was analyzed on
      the protein level in non-neoplastic mammary gland, primary mammary carcinomas,
      their lymph node metastases and intravascular tumor cells of 49 dogs, adenomas of
      49 dogs and non-neoplastic mammary gland of 98 dogs by immunohistochemistry. A
      significantly (p0.05) decreased percentage of p27 positive tissue samples was
      found when normal gland was compared with adenomas, carcinomas and lymph node
      metastases. Specifically, 91% of normal gland epithelium displayed nuclear p27
      expression. In contrast, only 22% of the adenomas, 20% of carcinomas, 12% of
      lymph node metastases and 32% of intravascular tumor cells had p27 reactivity.
      Cell cycle control by p27 is therefore lost in the majority of canine mammary
      tumors. The lack of significant differences between benign and malignant mammary
      tumors indicates that decreased p27 expression is an early step in carcinogenesis
      of canine mammary tumors and hinders the use of p27 as a marker of malignancy for
      this tumor type.

PMID- 19748646
TI  - Air-coupled ultrasonic assessment of wood veneer.
AB  - Air-coupled ultrasound (ACU) provides a tool to evaluate wood samples of small or
      moderate thickness (<30 mm) thereby avoiding direct contact or liquid coupling.
      Results of through-transmission ACU measurements on wood veneer samples and
      related products are reported with respect to a wide variety of quality aspects.
      Fluctuations in the averaged received signal levels appear to be correlated to
      the presence of natural or machine-induced thickness and density variations,
      flaws and grain damage, errors produced by the manufacturing process,
      insufficient bonding on a substrate, etc. In addition it is seen that the
      variability of the signal levels enables to distinguish between quarter and crown
      areas.

PMID- 19748647
TI  - Effective activation alleviates the replication block of CCR5-tropic HIV-1 in
      chimpanzee CD4+ lymphocytes.
AB  - Human immunodeficiency virus type 1 (HIV-1) originated in chimpanzees; yet,
      several previous studies have shown that primary HIV-1 isolates replicate poorly
      in chimpanzee CD4+ T lymphocytes in vitro and in vivo. The reasons for this
      apparent restriction are not understood. Here, we describe a new activation
      protocol that led to a reproducible expansion and activation of chimpanzee CD4+ T
      lymphocytes in vitro. Using this protocol, we uncovered species-specific
      differences in the activation profiles of human and chimpanzee CD4+ T-cells,
      including HLA-DR and CD62L. Moreover, we found that improved activation
      facilitated the replication of both CXCR4 and CCR5-tropic HIV-1 in CD4+ T-cell
      cultures from over 30 different chimpanzees. Thus, the previously reported
      "replication block" of CCR5-tropic HIV-1 in chimpanzee lymphocytes appears to be
      due, at least in large part, to suboptimal T-cell activation.

PMID- 19748648
TI  - Human monoclonal antibodies to SARS-coronavirus inhibit infection by different
      mechanisms.
AB  - SARS-CoV causes an acute infection making targeted passive immunotherapy an
      attractive treatment strategy. We previously generated human mAbs specific to the
      S1 region of SARS-CoV S protein. These mAbs bind epitopes within the receptor
      binding domain (RBD) or upstream of the RBD. We show that mAbs recognizing
      epitopes within the RBD inhibit infection by preventing viral attachment to the
      cellular receptor. One mAb binds upstream of the RBD and prevents viral entry by
      inhibiting a post-binding event. Evaluation of several mAbs demonstrated varying
      ability of the mAbs to select escape mutants when used individually. However, a
      mixture of antibodies could effectively neutralize a range of mutant viruses.
      These data strongly suggest that a mixture containing antibodies recognizing
      distinct regions and targeting more than one step in viral entry is likely to be
      more effective in neutralizing the virus and suppressing the generation of escape
      mutants, and thus potentially constitute a highly effective passive
      immunotherapy.

PMID- 19748649
TI  - A temperature sensitive mutant of heat shock protein 70 reveals an essential role
      during the early steps of tombusvirus replication.
AB  - By co-opting host proteins for their replication, plus-stranded RNA viruses can
      support robust replication and suppress host anti-viral responses. Tomato bushy
      stunt virus (TBSV) recruit the cellular heat shock protein 70 (Hsp70), an
      abundant cytosolic chaperone, into the replicase complex. By taking advantage of
      yeast model host, we demonstrate that the four-member SSA subfamily of HSP70
      genes is essential for TBSV replication. The constitutively expressed SSA1 and
      SSA2, which are resident proteins in the viral replicase, can be complemented by
      the heat-inducible SSA3 and/or SSA4 for TBSV replication. Using a yeast strain
      carrying a temperature sensitive ssa1(ts), but lacking functional SSA2/3/4, we
      show that inactivation of Ssa1p(ts) led to a defect in membrane localization of
      the viral replication proteins, resulting in cytosolic distribution of the viral
      proteins and lack of replicase activity. An in vitro replicase assembly assay
      with Ssa1p(ts) revealed that functional Ssa1p is required during the replicase
      assembly process, but not during minus- or plus-strand synthesis. Temperature
      shift experiments from nonpermissive to permissive in ssa1(ts) yeast revealed
      that the re-activated Ssa1p(ts) could promote efficient TBSV replication in the
      absence of other SSA genes. We also demonstrate that the purified recombinant
      Ssa3p can facilitate the in vitro assembly of the TBSV replicase on yeast
      membranes, demonstrating that Ssa3p can fully complement the function of Ssa1p.
      Taken together, the cytosolic SSA subfamily of Hsp70 proteins play essential and
      multiple roles in TBSV replication.

PMID- 19748650
TI  - The role of organic matter in the removal of emerging trace organic chemicals
      during managed aquifer recharge.
AB  - This study explored the effect of different bulk organic carbon matrices on the
      fate of trace organic chemicals (TOrC) during managed aquifer recharge (MAR).
      Infiltration through porous media was simulated in biologically active column
      experiments under aerobic and anoxic recharge conditions. Wastewater effluent
      derived organic carbon types, differing in hydrophobicity and biodegradability
      (i. e., hydrophobic acids, hydrophilic carbon, organic colloids), were used as
      feed substrates in the column experiments. These carbon substrates while fed at
      the same concentration differed in their ability to support soil biomass growth
      during porous media infiltration. Removal of degradable TOrC (with the exception
      of diclofenac and propyphenazone) was equal or better under aerobic versus anoxic
      porous media infiltration conditions. During the initial phase of infiltration,
      the presence of biodegradable organic carbon (BDOC) enhanced the decay of
      degradable TOrC by promoting soil biomass growth, suggesting that BDOC served as
      a co-substrate in a co-metabolic transformation of these contaminants. However,
      unexpected high removal efficiencies were observed for all degradable TOrC in the
      presence of low BDOC concentrations under well adopted oligotrophic conditions.
      It is hypothesized that removal under these conditions is caused by a specialized
      microbial community growing on refractory carbon substrates such as hydrophobic
      acids. Findings of this study reveal that the concentration and character of bulk
      organic carbon present in effluents affect the degradation efficiency for TOrC
      during recharge operation. Specifically aerobic, oligotrophic microbiological
      soil environments present favorable conditions for the transformation of TOrC,
      including rather recalcitrant compounds such as chlorinated flame retardants.

PMID- 19748651
TI  - Immobilization of mercury in sediment using stabilized iron sulfide
      nanoparticles.
AB  - Mercury (Hg) immobilization using stabilized iron sulfide (FeS) nanoparticles was
      investigated through a series of batch and column experiments. The nanoparticles
      were prepared using a low-cost, food-grade cellulose (sodium carboxymethyl
      cellulose, CMC) as the stabilizer. The hydrodynamic diameter of fresh FeS-CMC
      nanoparticles was measured to be 38.5+/-5.4nm. Batch tests showed that the
      nanoparticles can effectively immobilize Hg in a clay loam sediment. The Hg
      distribution coefficient for the nanoparticles was determined to be 8930+/
      1480L/g, which is >4 orders of magnitude greater than for the sediment. When the
      Hg-laden sediment was treated at an FeS-to-Hg molar ratio of 26.5, the Hg
      concentration leached into water was reduced by 97% and the TCLP (toxicity
      characteristic leaching procedure) leachability of Hg was reduced by 99%. Column
      tests showed that water-leachable mercury from the sediment containing 3120mg/L
      Hg was reduced by 67% and the TCLP leachability by >77% when the sediment was
      treated with 67 pore volumes (PVs) of a 0.5g/L FeS nanoparticle suspension.
      Column tests proved that the stabilized nanoparticles were highly mobile in the
      sediment and full breakthrough of the nanoparticles occurred at approximately 18
      PVs.

PMID- 19748652
TI  - Life history responses of Daphnia magna feeding on toxic Microcystis aeruginosa
      alone and mixed with a mixotrophic Poterioochromonas species.
AB  - The toxic effects of a mixotrophic golden alga (Poterioochromonas sp. strain ZX1)
      and a cyanobacterium Microcystis aeruginosa grazed by Poterioochromonas to a
      cladoceran were investigated through life history experiments using Daphnia
      magna. Poterioochromonas cultured in two ways (fed M. aeruginosa in an inorganic
      medium or grown in an organic medium) both induced starvation-like effects on D.
      magna, indicating that Poterioochromonas is neither acutely toxic nor a good food
      for D. magna. Despite a microcystin-LR content of 10(-8)microgcell(-1) in M.
      aeruginosa, no toxins were accumulated in Poterioochromonas fed the
      cyanobacterium. The toxic effect of M. aeruginosa to D. magna was significantly
      reduced in the presence of Poterioochromonas, which may be performed in two ways:
      decrease M. aeruginosa cells ingestion of D. magna by grazing on M. aeruginosa;
      and decrease the toxicity of the medium by degrading the toxins released by M.
      aeruginosa. This study provides new information on the interactions between a
      cyanobacterium and its grazer under laboratory conditions and may increase our
      understanding of the ecological significance of such interactions in the aquatic
      food webs.

PMID- 19748653
TI  - The effect of induced anoxia and reoxygenation on benthic fluxes of organic
      carbon, phosphate, iron, and manganese.
AB  - Eutrophication causes seasonally anoxic bottom waters in coastal environments,
      but we lack information on effects of onset of anoxia and subsequent
      reoxygenation on benthic fluxes of redox-sensitive minerals and associated
      organic carbon (OC). As the first study, we determined the effect of inducing
      anoxia and subsequently restoring oxic conditions in mesocosms with surface
      sediment and water from a coastal environment. These concentration changes were
      compared with those in an oxygenated control. We determined water column
      concentrations of dissolved organic carbon (DOC), particulate organic carbon
      (POC), iron, manganese, and phosphate. Benthic fluxes of DOC, POC, and iron
      increased at the onset of anoxia in oxygen-depleted treatments. DOC and iron
      concentrations increased concomitantly towards maxima, which may have indicated
      reductive dissolution of FeOOH and release of associated OC. The subsequent
      concomitant concentration decreases may have been the result of coprecipitation
      of OC with iron-containing minerals. In contrast, the phosphate-concentration
      increase occurred several days after the onset of anoxia and the manganese
      concentration was not affected by the onset of anoxia. Restoring oxic conditions
      resulted in a decrease in DOC, POC, and phosphate concentrations, which may
      indicate coprecipitation of OC with phosphate-containing minerals. The high DOC
      fluxes at the onset of anoxia indicate that redox oscillations may be important
      in OC degradation. Further, our results indicate a close coupling between OC
      cycling and dissolution/precipitation of iron-containing minerals in
      intermittently anoxic sediments.

PMID- 19748654
TI  - Adult brain nitrergic activity after concomitant prenatal exposure to ethanol and
      methyl mercury.
AB  - Pregnant rats were exposed to ethanol (EtOH) and/or methyl mercury (MeHg) during
      fetal brain development. Nitrergic activity was quantified by densitometric
      measurement of formazan deposits in the hippocampus, cerebellum and striatum of
      two-month-old offspring following histochemical assay for NADPH-diaphorase (NADPH
      d) activity. Compared to control subjects, an increase in nitrergic activity was
      found in the molecular layer of dentate gyrus and in the lacunosum molecular and
      stratum radiatum of CA1 (cornus amoni 1) in the EtOH+MeHg group, whereas a single
      administration of EtOH increased the activity in all striatal segments. The
      cerebellum seems to be less sensitive at this time-point to intoxication, and
      presented an increase only at the molecular layer of EtOH-exposed animals when
      compared to the MeHg and EtOH+MeHg groups (ANOVA, one-way followed by Tukey's
      test, p<0.05 or p<0.01). Taken together, results suggest that developmental
      exposure to EtOH and MeHg, singularly or in combination, alters nitrergic
      activity in adult rat in different ways depending on the region and layer of the
      central nervous system (CNS), and that these alterations might be related to
      different local metabolic properties.

PMID- 19748655
TI  - Human subjects are protected from mast cell tryptase deficiency despite frequent
      inheritance of loss-of-function mutations.
AB  - BACKGROUND: Mast cell tryptases have proposed roles in allergic inflammation and
      host defense against infection. Tryptase gene loci TPSAB1 and TPSB2 are known to
      be polymorphic, but the nature and extent of diversity at these loci have not
      been fully explored. OBJECTIVE: We sought to compare functional and nonfunctional
      tryptase allele frequencies and establish haplotypes in human populations.
      METHODS: Tryptase allele frequencies were determined by means of direct
      sequencing in 270 individuals from HapMap populations of European, African,
      Chinese, and Japanese ancestry. Haplotypes were predicted, validated in parent
      child trios, and compared between populations. RESULTS: We identify a new frame
      shifted tryptase allele (betaIII(FS)) carried by 23% and 19% of individuals of
      European and African ancestry but 0% of Asian subjects. Homology models predict
      that betaIII(FS) is functionless. Our genotyping assay shows that allele and
      haplotype distributions in each population are unique. Strong linkage
      disequilibrium between TPSAB1 and TPSB2 (r(2)=0.83, D'=0.85) yields 2 major and 5
      minor tryptase haplotypes. CONCLUSIONS: Tryptase deficiency alleles (alpha and
      the newly discovered betaIII(FS)) are common, causing the number of inherited
      active genes to range from a minimum of 2 to a maximum of 4, with major
      differences between populations in the proportion of individuals inheriting 2
      versus 4 active alleles. African and Asian populations are especially enriched in
      genes encoding functional and nonfunctional tryptases, respectively. Strong
      linkage of TPSAB1 and TPSB2 and pairing of deficiency alleles with functional
      alleles in observed haplotypes protect human subjects from "knockout" genomes and
      indeed from inheritance of fewer than 2 active alleles.

PMID- 19748656
TI  - Clinical studies of the DP1 antagonist laropiprant in asthma and allergic
      rhinitis.
AB  - BACKGROUND: Prostaglandin D(2) is a proinflammatory mediator believed to be
      important in asthma and allergic rhinitis (AR). Allelic variants in the
      prostaglandin D(2) receptor type 1 (DP1) gene (PTGDR) have been suggested to be
      associated with asthma susceptibility. OBJECTIVES: We sought to investigate the
      efficacy of the DP1 antagonist laropiprant (alone or with montelukast) in asthma
      and seasonal AR and explore whether sequence variations in PTGDR are associated
      with asthma severity. METHODS: For asthma, in a double-blind crossover study, 100
      patients with persistent asthma were randomized to placebo or laropiprant, 300
      mg/d for 3 weeks, followed by addition of montelukast, 10 mg/d for 2 weeks. PTGDR
      promoter haplotypes were categorized as high, medium, or low transcriptional
      efficiency. The primary efficacy end point was FEV(1). For AR, in a double-blind
      parallel-group study, 767 patients sensitized to a regionally prevalent fall
      allergen with symptomatic fall rhinitis were allocated to laropiprant, 25 mg/d or
      100 mg/d; cetirizine, 10mg/d; or placebo for 2 weeks. The primary end point was
      the Daytime Nasal Symptoms Score. RESULTS: For asthma, no significant differences
      in FEV(1) or asthma symptoms were noted for laropiprant versus placebo or
      laropiprant plus montelukast vs montelukast (differences between montelukast and
      placebo: P <or= .001). No clear association was seen between haplotype pair (ie,
      diplotype) and asthma severity. For AR, although cetirizine (vs placebo)
      demonstrated an improvement in the Daytime Nasal Symptoms Score (P < .001),
      laropiprant did not. CONCLUSION: Laropiprant did not demonstrate efficacy in
      asthmatic patients or patients with AR. Variations in PTGDR did not appear
      related to baseline asthma severity or treatment response (NCT00533208;
      NCT00783601).

PMID- 19748657
TI  - Maternal interpersonal trauma and cord blood IgE levels in an inner-city cohort:
      a life-course perspective.
AB  - BACKGROUND: Prenatal stress affects immunocompetence in offspring, although the
      underlying mechanisms are not well understood. OBJECTIVE: We sought to examine
      associations between maternal lifetime interpersonal trauma (IPT) and cord blood
      total IgE levels in a sample of urban newborns (n = 478). METHODS: Maternal IPT
      during childhood and adolescence (birth to 17 years), adulthood (18 years to
      index pregnancy), and the index pregnancy were ascertained by using the Revised
      Conflict Tactics Scale at 28.4 +/- 7.9 weeks' gestation. Cord blood IgE levels
      were derived by using a fluoroenzyme immunoassay. We examined effects of maternal
      IPT on increased cord blood IgE levels (upper quartile, 1.08 IU/mL) by using
      logistic regression, adjusting for confounders and mediating variables. RESULTS:
      Maternal trauma was categorized as unexposed (n = 285 [60%]), early (childhood
      and/or teenage years only, n = 107 [22%]), late (adulthood and/or index pregnancy
      only, n = 29 [6%]), and chronic (early and late, n = 57 [12%]) exposure. Relative
      to no IPT, early (odds ratio [OR], 1.78; 95% CI, 1.05-3.00) and chronic maternal
      IPT (OR, 2.25; 95% CI, 1.19-4.24) were independently associated with increased
      IgE levels in unadjusted analyses. When adjusting for standard controls,
      including maternal age and race, season of birth, child's sex, and childhood and
      current socioeconomic status, early effects became nonsignificant (OR, 1.48; 95%
      CI, 0.85-2.58). Chronic exposure remained significant in fully adjusted models,
      including standard controls, current negative life events, allergen exposure, and
      potential pathway variables (maternal atopy, prenatal smoking, and birth weight;
      OR, 2.18; 95% CI, 1.06-4.50). CONCLUSION: These data link chronic trauma over the
      mother's life course with increased IgE levels in infants at birth. Research
      examining associations between maternal trauma and indicators of offspring's
      atopic risk might be particularly relevant in inner-city high-risk populations.

PMID- 19748658
TI  - Peeling off the layers: skin taping and a novel proteomics approach to study
      atopic dermatitis.

PMID- 19748659
TI  - Selective control of SIRP-alpha-positive airway dendritic cell trafficking
      through CD47 is critical for the development of T(H)2-mediated allergic
      inflammation.
AB  - BACKGROUND: Dendritic cells (DCs) are essential for the initiation and
      maintenance of T(H)2 responses to inhaled antigen that lead to the establishment
      of allergic diseases. Two subpopulations of nonplasmacytoid DCs (ie,
      CD11b(low)CD103+ and CD11b(high)CD103(-)) are found in lung/airway tissues. Yet
      the identification and migratory properties of the DC subset that contributes to
      T(H)2-mediated responses remain to be clarified. CD47, a signal regulatory
      protein (SIRP)-alpha partner, reportedly governed skin DC migration. OBJECTIVE:
      We here thought to investigate the role of CD47/SIRP-alpha interactions in airway
      DC trafficking and the development of allergic airway inflammation. METHODS: We
      characterized the DC influx into lungs and mediastinal lymph nodes in CD47(-/-)
      and CD47(+/+) BALB/c mice by using experimental models of allergic asthma. Mice
      were systemically (intraperitoneal ovalbumin/alum) or locally (intratracheal
      ovalbumin-loaded bone marrow-derived DCs) immunized and challenged by ovalbumin
      aerosol. We also evaluated the consequences of SIRP-alpha-Fc fusion molecule
      administration on the induction of airway disease in BALB/c mice. RESULTS: SIRP
      alpha selectively identified the CD11b(high)CD103(-) DC subset that predominantly
      accumulated in mediastinal lymph nodes during airway inflammation. However,
      CD103(-)SIRP-alpha+ DC trafficking, T(H)2 responses, and airway disease were
      impaired in CD47(-/-) mice. Importantly, the adoptive transfer of CD103(-) SIRP
      alpha+CD47(+/+) but not CD47(-/-) DCs elicited a strong T(H)2 response in CD47(-/
      ) mice. Finally, the administration of SIRP-alpha-Fc molecule protected BALB/c
      mice from allergic airway inflammation. CONCLUSION: Lung CD11b(high)CD103(-)SIRP
      alpha+ DC migration is governed by self-CD47 expression, and manipulation of the
      CD47/SIRP-alpha pathway suppresses CD103(-)SIRP-alpha(+) DC-driven pathogenic
      T(H)2 responses and airway inflammation.

PMID- 19748660
TI  - Process quality measures and asthma exacerbations in the medicaid population.
AB  - BACKGROUND: Asthma quality assessment often focuses on controller medication use,
      yet claims-based studies find conflicting associations between this care process
      and clinical outcomes. OBJECTIVE: We sought to compare the association between 3
      controller-based quality measures and asthma exacerbations to gain better
      understanding of how processes of care are related to clinical outcomes. METHODS:
      Identifying a cohort of Medicaid beneficiaries with persistent asthma by using
      Healthcare Effectiveness Data and Information Set (HEDIS) criteria for asthma in
      2001-2002 in California and New York, we assessed 3 asthma quality metrics in
      2002: (1) the current HEDIS measure of at least 1 controller medication filling;
      (2) at least 4 controller medication prescription fillings; and (3) a controller
      to-total asthma medication ratio of at least 0.5. We calculated the odds of
      having an asthma exacerbation in 2003 as a function of performance on each
      quality metric, adjusting for race, sex, age, and prior outpatient and acute care
      use for asthma. RESULTS: Of 90,909 subjects with persistent asthma in California
      (48.1%) and New York (51.9%), those who obtained at least 1 or at least 4
      controller medications had increased likelihood of poor outcomes (adjusted odds
      ratios, 1.80 [95% CI, 1.73-1.87] and 1.44 [95% CI 1.40-1.48], respectively).
      Beneficiaries meeting the controller-to-total asthma medication ratio measure
      were 23.0% less likely to have exacerbations (adjusted odds ratio, 0.77 [95% CI,
      0.75-0.80]). CONCLUSIONS: A higher controller medication ratio indicated a lower
      likelihood of asthma exacerbations, whereas assessing the number of controller
      medication-dispensing events was associated with a higher odds of exacerbation.

PMID- 19748661
TI  - Fractional exhaled nitric oxide measurements are most closely associated with
      allergic sensitization in school-age children.
AB  - BACKGROUND: Factors affecting fractional exhaled nitric oxide (FeNO) in early
      childhood are incompletely understood. OBJECTIVE: To examine the relationships
      between FeNO and allergic sensitization, total IgE, atopic dermatitis, rhinitis,
      asthma, and lung function (spirometry) in children. METHODS: Children at high
      risk of asthma and other allergic diseases because of parental history were
      enrolled at birth and followed prospectively. FeNO was measured by an online
      technique at ages 6 and 8 years. Relationships among FeNO, various atopic
      characteristics, and asthma were evaluated. RESULTS: Reproducible FeNO
      measurements were obtained in 64% (135/210) of 6-year-old and 93% (180/194) of 8
      year-old children. There was seasonal variability in FeNO. Children with
      aeroallergen sensitization at ages 6 and 8 years had increased levels of FeNO
      compared with those not sensitized (geometric mean; 6 years, 10.9 vs 6.7 parts
      per billion [ppb], P < .0001; 8 years, 14.6 vs 7.1 ppb, P < .0001). FeNO was
      higher in children with asthma than in those without asthma at 8 years but not 6
      years of age (6 years, 9.2 vs 8.3 ppb, P = .48; 8 years, 11.5 vs 9.2 ppb, P =
      .03). At 8 years of age, this difference was no longer significant in a
      multivariate model that included aeroallergen sensitization (P = .33). There were
      no correlations between FeNO and spirometric indices at 6 or 8 years of age.
      CONCLUSION: These findings underscore the importance of evaluating allergen
      sensitization status when FeNO is used as a potential biomarker in the diagnosis
      and/or monitoring of atopic diseases, particularly asthma.

PMID- 19748662
TI  - Adjustment for baseline value in the analysis of change in FEV1 over time.

PMID- 19748663
TI  - Concentrations of 15-ketodihydro-PGF2alpha, cortisol, and progesterone in the
      plasma of healthy and pathologic newborn foals.
AB  - Information regarding the plasma hormone profiles of prostaglandins (PGs),
      cortisol (C), and progesterone (P4) during pathologic processes in newborn foals
      is scarce. The aim of this study was to determine the plasma concentrations of
      these hormones in diseased foals (n=40) and healthy at-term foals (n=24) (Equus
      caballus) during the first 2 weeks of life. Blood samples were collected daily,
      before any treatment with nonsteroidal drugs in diseased foals, and plasma was
      analyzed by radioimmunoassay. 15-Ketodihydro-PGF(2alpha) (PGM) was consistently
      higher in diseased foals than in healthy foals, probably related to roles of PGs
      in completing organ maturation and/or the presence of oxidative stress or
      inflammation. Similar trends were observed for C and P4. In diseased newborns,
      only PGM was significantly higher in nonsurviving foals, although C showed a
      similar profile. When specific diseases were considered, the levels of PGM and C
      were lower in premature foals at 12h of life, whereas the concentration of P4 was
      higher than in controls. The results of this study demonstrate the differences in
      plasma hormone levels between healthy and pathologic newborn foals, particularly
      during the first 2 d of life, probably reflecting the inability of diseased foals
      to cope with the transition between fetal and neonatal life.

PMID- 19748664
TI  - Effects of ammonium hexafluorosilicate concentration on dentin tubule occlusion
      and composition of the precipitate.
AB  - Ammonium hexafluorosilicate [SiF: (NH(4))(2)SiF(6)] was prepared in order to
      overcome the tooth discoloration caused by diamine silver fluoride [AgF:
      (NH(3))(2)AgF] application. We employed a single concentration of SiF solution in
      our previous study; therefore, it is still unclear how the concentration of SiF
      solution affects the occlusion of dentin tubules and composition of the
      precipitate. OBJECTIVE: The aim of this study was to evaluate the effects of
      changing the concentration of SiF on its clinical use as a dentin
      hypersensitivity treatment. METHODS: To simulate dentin tubules subject to dentin
      hypersensitivity, dentin disks were treated with EDTA for 2 min. Then, the disks
      were treated with several concentrations of SiF solution (from 100 to 19,400 ppm)
      for 3 min. The occlusion of dentin tubules was evaluated using scanning electron
      microscopy (SEM), and the composition of the precipitate formed in the tubules
      after SiF treatment was assessed using energy dispersive X-ray analysis (EDXA).
      RESULTS: SEM photographs demonstrated that dentin tubules after treatment with
      SiF were occluded homogeneously and fully regardless of the concentration of SiF
      solution. The Ca/P molar ratio of the precipitate formed in dentin tubules after
      SiF treatment was increased with the concentration of SiF solution. SIGNIFICANCE:
      It was concluded that the capacity to occlude dentin tubules was the same
      regardless of the concentration of SiF solution. However, the composition of the
      precipitate formed in the tubules was dependent on the concentration of SiF
      solution.

PMID- 19748665
TI  - A selective endothelin-receptor antagonist to reduce blood pressure in patients
      with treatment-resistant hypertension: a randomised, double-blind, placebo
      controlled trial.
AB  - BACKGROUND: Hypertension cannot always be adequately controlled with available
      drugs. We investigated the blood-pressure-lowering effects of the new
      vasodilatory, selective endothelin type A antagonist, darusentan, in patients
      with treatment-resistant hypertension. METHODS: This randomised, double-blind
      study was undertaken in 117 sites in North and South America, Europe, New
      Zealand, and Australia. 379 patients with systolic blood pressure of 140 mm Hg or
      more (>/=130 mm Hg if patient had diabetes or chronic kidney disease) who were
      receiving at least three blood-pressure-lowering drugs, including a diuretic, at
      full or maximum tolerated doses were randomly assigned to 14 weeks' treatment
      with placebo (n=132) or darusentan 50 mg (n=81), 100 mg (n=81), or 300 mg (n=85)
      taken once daily. Randomisation was made centrally via an automated telephone
      system, and patients and all investigators were masked to treatment assignments.
      The primary endpoints were changes in sitting systolic and diastolic blood
      pressures. Analysis was by intention to treat. The study is registered with
      ClinicalTrials.gov, number NCT00330369. FINDINGS: All randomly assigned
      participants were analysed. The mean reductions in clinic systolic and diastolic
      blood pressures were 9/5 mm Hg (SD 14/8) with placebo, 17/10 mm Hg (15/9) with
      darusentan 50 mg, 18/10 mm Hg (16/9) with darusentan 100 mg, and 18/11 mm Hg
      (18/10) with darusentan 300 mg (p<0.0001 for all effects). The main adverse
      effects were related to fluid accumulation. Oedema or fluid retention occurred in
      67 (27%) patients given darusentan compared with 19 (14%) given placebo. One
      patient in the placebo group died (sudden cardiac death), and five patients in
      the three darusentan dose groups combined had cardiac-related serious adverse
      events. INTERPRETATION: Darusentan provides additional reduction in blood
      pressure in patients who have not attained their treatment goals with three or
      more antihypertensive drugs. As with other vasodilatory drugs, fluid management
      with effective diuretic therapy might be needed. FUNDING: Gilead Sciences.

PMID- 19748666
TI  - Resistant hypertension: an unmet treatment need.

PMID- 19748667
TI  - The monozygotic twinning process, the twin-twin transfusion syndrome and acardiac
      twins.
AB  - This paper suggests that during the time of the "splitting process" that produces
      monozygotic twins the number of cells may not be evenly distributed to the future
      twins. The outcome of this 'irregular division' may be the twin-to-twin
      transfusion syndrome and acardiac twins.

PMID- 19748668
TI  - Plumbagin induces ROS-mediated apoptosis in human promyelocytic leukemia cells in
      vivo.
AB  - Plumbagin, a naphtoquinone from the roots of Plumbago zeylanica is known to
      possess anticancer and anti-bacterial activity. Based on the former finding of
      our group in vitro demonstrating its effectiveness in human promyelocytic
      leukemia cells, NB4, in this study we further revealed the mitochondrial pathway
      involved in plumbagin-induced apoptosis. We also found that the generation of ROS
      was a critical mediator in plumbagin-induced apoptosis, which would be abrogated
      completely by antioxidant, NAC. The anticancer effect of plumbagin was
      investigated in vivo using NB4 tumor xenograft in NOD/SCID mice. The incidence of
      formation, growth characteristics, body weight and volume of tumors were
      observed. The histopathologic examination of tumors and organs were made. The
      results showed that intraperitoneal injection of plumbagin (2mg/kg body weight)
      daily for 3 weeks resulted to a 64.49% reduction of tumor volume compared with
      the control. Furthermore, there was no overt manifestation of toxicity such as
      weight loss, tissue damage and behavior change which appeared in Doxorubicin
      treated mice (1mg/kg thrice a week). These results indicate that plumbagin has
      potential as a novel therapeutic agent for myeloid leukemia.

PMID- 19748669
TI  - In vitro secretion of matrix metalloprotease 9 is a prognostic marker in
      childhood acute lymphoblastic leukemia.
AB  - Matrix metalloproteases (MMPs) are endopeptidases involved in tumor cell
      invasion. Childhood acute lymphoblastic leukemia (ALL) is characterized by its
      capacity to infiltrate different organs. We analyzed the expression of MMP-2, -9,
      -14 and TIMP-1 and -2 in a prospective study on 86 children with newly diagnosed
      ALL (73 B- and 13 T-lineage) and 9 children at relapse with B-ALL. Membrane-bound
      and intracytoplasmic MMPs and TIMPs were analyzed by flow cytometry, and secreted
      MMPs were quantified by ELISA. In patients at relapse, MMP-14 was present in a
      greater proportion of the B-ALL cell population than at diagnosis. In patients
      with peripheral infiltration, intracytoplasmic MMP-9 was significantly higher
      than in patients without infiltration. ROC curve and Kaplan-Meier curve analysis
      showed that a high secretion of MMP-9 (>2450 pg/ml/10(6) cells) was associated
      with a lower overall survival rate, suggesting that the secretion of MMP-9 is an
      independent prognostic factor in childhood B-ALL.

PMID- 19748670
TI  - Expression pattern of the septin gene family in acute myeloid leukemias with and
      without MLL-SEPT fusion genes.
AB  - Septins are proteins associated with crucial steps in cell division and cellular
      integrity. In humans, 14 septin genes have been identified, of which five (SEPT2,
      SEPT5, SEPT6, SEPT9, and SEPT11) are known to participate in reciprocal
      translocations with the MLL gene in myeloid neoplasias. We have recently shown a
      significant down-regulation of both SEPT2 and MLL in myeloid neoplasias with the
      MLL-SEPT2 fusion gene. In this study, we examined the expression pattern of the
      other 13 known septin genes in altogether 67 cases of myeloid neoplasia,
      including three patients with the MLL-SEPT2 fusion gene, four with MLL-SEPT6
      fusion, and three patients with the MLL-SEPT9 fusion gene. When compared with
      normal controls, a statistically significant down-regulation was observed for the
      expression of both MLL (6.4-fold; p=0.008) and SEPT6 (1.7-fold; p=0.002) in MLL
      SEPT6 leukemia. Significant down-regulation of MLL was also found in MLL-MLLT3
      leukemias. In addition, there was a trend for SEPT9 down-regulation in MLL-SEPT9
      leukemias (4.6-fold; p=0.077). Using hierarchical clustering analysis to compare
      acute myeloid leukemia genetic subgroups based on their similarity of septin
      expression changes, we found that MLL-SEPT2 and MLL-SEPT6 neoplasias cluster
      together apart from the remaining subgroups and that PML-RARA leukemia presents
      under-expression of most septin family genes.

PMID- 19748671
TI  - Response to imatinib in a patient with chronic myeloid leukemia simultaneously
      expressing p190(BCR-ABL) oncoprotein and JAK2V617F mutation.

PMID- 19748672
TI  - Phase I trials of amonafide as monotherapy and in combination with cytarabine in
      patients with poor-risk acute myeloid leukemia.
AB  - Amonafide-l-malate (amonafide) is a unique DNA intercalator that maintains
      activity in the presence of MDR mechanisms, a frequent cause of treatment-failure
      in secondary AML. 43 patients with relapsed/refractory or secondary AML or CML
      blast crisis were enrolled into two phase I dose-escalation studies investigating
      amonafide as monotherapy or in combination with cytarabine. 3/17 patients in the
      monotherapy trial and 10/26 patients in the combination trial achieved a complete
      remission. Between both trials responses occurred in 9/20 patients with secondary
      AML. Both trials demonstrated an acceptable safety profile and significant
      antileukemic activity in patients with poor-risk AML, especially those with
      secondary AML.

PMID- 19748673
TI  - Child pornography in peer-to-peer networks.
AB  - OBJECTIVE: The presence of child pornography in peer-to-peer networks is not
      disputed, but there has been little effort done to quantify and analyze the
      distribution and nature of that content to-date. By performing an analysis of
      queries and query hits on the largest peer-to-peer network, we are able to both
      quantify and describe the nature of querying by child pornographers as well as
      the content they are sharing. METHOD: Child pornography related content was
      identified and analyzed in 235,513 user queries and 194,444 query hits. RESULTS:
      The research confirmed a large amount of peer-to-peer traffic is dedicated to
      child pornography, but supply and demand must be separated for a better
      understanding. The most prevalent query and the top two most prevalent filenames
      returned as query hits were child pornography related. However, it would be
      inaccurate to state child pornography dominates peer-to-peer as 1% of all queries
      were related to child pornography and 1.45% of all query hits (unique filenames)
      were related to child pornography, consistent with a smaller study (Hughes et
      al., 2008). In addition to the above, research indicates that the median age
      searched for was 13 years old, and the majority of queries were gender-neutral,
      but of those with gender-related terms, 79% were female-oriented. Distribution
      wise, the vast majority of content-specific searches are for movies at 99%,
      though images are still the most prevalent in availability. CONCLUSIONS: There is
      no shortage of child pornography supply and demand on peer-to-peer networks and
      by analyzing how consumers seek and distributors advertise content we can better
      understand their motivations. PRACTICE IMPLICATIONS: Understanding the behavior
      of child pornographers and how they search for content when contrasted with those
      sharing content provides a basis for finding and combating that behavior. For law
      enforcement, knowing the specific terms used allows more timely and accurate
      forensics and better identification of those seeking and distributing child
      pornography. For Internet researchers, better filtering and monitoring is
      possible. For mental health professionals, understanding the preferences and
      behaviors of those searching supports more effective treatment.

PMID- 19748674
TI  - Crystal structure of an anti-ganglioside antibody, and modelling of the
      functional mimicry of its NeuGc-GM3 antigen by an anti-idiotypic antibody.
AB  - N-Glycolylated (NeuGc) gangliosides are tumor-specific antigens and as such
      represent attractive targets for cancer immunotherapy. The chimeric antibody chP3
      selectively recognizes a broad variety of NeuGc gangliosides, showing no cross
      reactivity to the highly similar N-acetylated (NeuAc) gangliosides that are
      common cellular antigens in humans. Here, we report the crystal structure of the
      chP3 Fab and its computer-docking model with the trisaccharide
      NeuGcalpha3Galbeta4Glcbeta, which represents the carbohydrate moiety of the tumor
      antigen NeuGc-GM3. The interaction involves only the heavy chain of the chP3
      antibody. The modelled complex is consistent with all available experimental data
      and shows good surface complementarity. The negatively charged sialic acid
      residue NeuGc is buried in a pocket flanked by two arginine residues, VH Arg31
      and VH Arg100A. We have further investigated the interaction of chP3 with its
      anti-idiotypic antibody, 1E10 (also known as Racotumomab), currently in clinical
      trials as a cancer vaccine. While many of the chP3 residues predicted to interact
      with the NeuGc ganglioside also feature prominently in the modelled complex of
      chP3 and 1E10, we do not observe structural mimicry. Rather, we suspect that the
      anti-idiotype 1E10 may serve as an imprint of the structural characteristics of
      the chP3 idiotype and, consequently, give rise to antibodies with P3-like
      properties upon immunization.

PMID- 19748675
TI  - Photodynamic therapy and intravitreal triamcinolone for neovascular age-related
      macular degeneration: a randomized clinical trial.
AB  - PURPOSE: To evaluate the efficacy of intravitreal triamcinolone acetonide (ITA)
      as an adjunct to photodynamic therapy with verteprofin (VPDT) in the treatment of
      predominantly classic, subfoveal choroidal neovascularization (CNV) owing to age
      related macular degeneration (AMD). DESIGN: A multicenter, 2-year, double-blind,
      randomized, sham-controlled trial conducted at 11 sites in Canada. PARTICIPANTS
      AND CONTROLS: One hundred individuals over the age of 50 were randomized 1:1 to
      either to VPDT alone or combined VPDT and ITA. INTERVENTION: Participants all
      received full-fluence VPDT and were randomly assigned to either (1) a same-day
      injection of 4 mg ITA or (2) a sham intraocular injection. MAIN OUTCOME MEASURE:
      The primary end point was the change in numbers of letters read between baseline
      and 1 year. RESULTS: Combination therapy with VPDT and ITA when compared with
      VPDT therapy alone resulted in no significant difference in final visual acuity
      at 1 year. Eyes treated with combination therapy lost an average of 17 letters
      compared with 20 letters for the VPDT group. Subjects receiving ITA required
      significantly fewer retreatments over the course of the study (1.28 vs 1.94,
      respectively; P = 0.003). Although elevated intraocular pressures were noted in a
      larger proportion of subjects receiving ITA, all of these individuals were
      managed successfully with topical ocular antihypertensive agents. CONCLUSIONS:
      There was no visual benefit to the addition of intravitreal triamcinolone to
      VPDT. Combination therapy, however, can reduce the number of VPDT treatments
      required by subjects who have predominantly classic CNV owing to AMD. This
      reduced treatment quantity needs to be weighed against potential side effects.
      (ClinicalTrials.gov number, NCT00148551).

PMID- 19748676
TI  - Methotrexate for ocular inflammatory diseases.
AB  - PURPOSE: To evaluate the outcome of treatment with methotrexate for noninfectious
      ocular inflammation. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients
      with noninfectious ocular inflammation managed at 4 tertiary ocular inflammation
      clinics in the United States observed to add methotrexate as a single,
      noncorticosteroid immunosuppressive agent to their treatment regimen, between
      1979 and 2007, inclusive. METHODS: Participants were identified from the Systemic
      Immunosuppressive Therapy for Eye Diseases Cohort Study. Demographic and clinical
      characteristics, including dosage, route of administration of methotrexate, and
      main outcome measures, were obtained for every eye of every patient at every
      visit via medical record review by trained expert reviewers. MAIN OUTCOME
      MEASURES: Control of inflammation, corticosteroid-sparing effects, and incidence
      of and reason for discontinuation of therapy. RESULTS: Among 384 patients (639
      eyes) observed from the point of addition of methotrexate to an anti-inflammatory
      regimen, 32.8%, 9.9%, 21.4%, 14.6%, 15.1%, and 6.3%, respectively, had anterior
      uveitis, intermediate uveitis, posterior or panuveitis, scleritis, ocular mucous
      membrane pemphigoid, and other forms of ocular inflammation. In these groups,
      complete suppression of inflammation sustained for >or=28 days was achieved
      within 6 months in 55.6%, 47.4%, 38.6%, 56.4%, 39.5%, and 76.7%, respectively.
      Corticosteroid-sparing success (sustained suppression of inflammation with
      prednisone <or=10 mg/d) was achieved within 6 months among 46.1%, 41.3%, 20.7%,
      37.3%, 36.5%, and 50.9%, respectively. Overall, success within 12 months was 66%
      and 58.4% for sustained control and corticosteroid sparing (<or=10 mg),
      respectively. Methotrexate was discontinued within 1 year by 42% of patients. It
      was discontinued owing to ineffectiveness in 50 patients (13%); 60 patients (16%)
      discontinued because of side effects, which typically were reversible with dose
      reduction or discontinuation. Remission was seen in 43 patients, with 7.7%
      remitting within 1 year of treatment. CONCLUSIONS: Our data suggest that adding
      methotrexate to an anti-inflammatory regimen not involving other
      noncorticosteroid immunosuppressive drugs is moderately effective for management
      of inflammatory activity and for achieving corticosteroid-sparing objectives,
      although many months may be required for therapeutic success. Methotrexate was
      well tolerated by most patients, and seems to convey little risk of serious side
      effects during treatment.

PMID- 19748677
TI  - The effect of beverage preparation method on aluminium content in coffee
      infusions.
AB  - Seven types of coffee were prepared by four methods. Three of them - simple
      coffee infusion, preparation in ibrick and moka pot - are very often used to
      prepare coffee at home. The fourth one - a single-cup filter is typical for
      Vietnam. Cookware used for each method was made from glass, aluminium, stainless
      steel and two types of alloys. Amounts of Al leaching to coffee infusions were
      determined. On average, the highest amount of Al was in coffee infusions brewed
      in aluminium single-cup filter, and the lowest in infusions prepared by simple
      extraction. Other brewing methods in combination with different tool materials
      resulted in similar Al content. The type of brewing method significantly
      influences the Al content in final infusion. Aluminium content varies in
      infusions in relation to the method of choice, especially when using single-cup
      filter. Despite the fact that coffee is considered to be a poor source of Al for
      humans, in some cases, Al content in infusions can even reach the values reported
      for tea infusions.

PMID- 19748678
TI  - Long-term changes in aluminum fractions of drainage waters in two forest
      catchments with contrasting lithology.
AB  - Aluminum (Al) chemistry was studied in soils and waters of two catchments covered
      by spruce (Picea abies) monocultures in the Czech Republic that represent
      geochemical end-members of terrestrial and aquatic sensitivity to acidic
      deposition. The acid-sensitive Lysina catchment, underlain by granite, was
      compared to the acid-resistant Pluhuv Bor catchment on serpentine. Organically
      bound Al was the largest pool of reactive soil Al at both sites. Very high median
      total Al (Alt) concentrations (40 micromol L(-1)) and inorganic monomeric Al
      (Ali) concentrations (27 micromol L(-1)) were observed in acidic (pH 4.0) stream
      water at Lysina in the 1990s and these concentrations decreased to 32 micromol L(
      1) (Alt) and 13 micromol L(-1) (Ali) in the 2000s. The potentially toxic Ali
      fraction decreased in response to long-term decreases in acidic deposition, but
      Ali remained the largest fraction. However, the organic monomeric (Alo) and
      particulate (Alp) fractions increased in the 2000s at Lysina. In contrast to
      Lysina, marked increases of Alt concentrations in circum-neutral waters at Pluhuv
      Bor were observed in the 2000s in comparison with the 1990s. These increases were
      entirely due to the Alp fraction, which increased more than 3-fold in stream
      water and up to 8-fold in soil water in the A horizon. Increase of Alp coincided
      with dissolved organic carbon (DOC) increases. Acidification recovery may have
      increased the content of colloidal Al though the coagulation of monomeric Al.

PMID- 19748679
TI  - Long-term persistence of vaccine-derived aluminum hydroxide is associated with
      chronic cognitive dysfunction.
AB  - Macrophagic myofasciitis (MMF) is an emerging condition, characterized by
      specific muscle lesions assessing long-term persistence of aluminum hydroxide
      within macrophages at the site of previous immunization. Affected patients mainly
      complain of arthromyalgias, chronic fatigue, and cognitive difficulties. We
      designed a comprehensive battery of neuropsychological tests to prospectively
      delineate MMF-associated cognitive dysfunction (MACD). Compared to control
      patients with arthritis and chronic pain, MMF patients had pronounced and
      specific cognitive impairment. MACD mainly affected (i) both visual and verbal
      memory; (ii) executive functions, including attention, working memory, and
      planning; and (iii) left ear extinction at dichotic listening test. Cognitive
      deficits did not correlate with pain, fatigue, depression, or disease duration.
      Pathophysiological mechanisms underlying MACD remain to be determined. In
      conclusion, long-term persistence of vaccine-derived aluminum hydroxide within
      the body assessed by MMF is associated with cognitive dysfunction, not solely due
      to chronic pain, fatigue and depression.

PMID- 19748680
TI  - Theory of mind impairments in euthymic bipolar patients.
AB  - BACKGROUND: Deficits in social cognition, e.g. theory of mind (ToM) represent
      core characteristics involved in the etiology of psychopathological symptoms and
      an important predictor of social competence. In bipolar affective disorder,
      evidence for ToM deficits is scant, although brain imaging studies and
      impairments in non-social neurocognitive domains indicate deficits of prefrontal
      functions. METHODS: Twenty-nine euthymic patients with bipolar affective disorder
      and 29 matched healthy controls were examined with the 'Movie for the Assessment
      of Social Cognition' (MASC). Target parameters comprised 1) 'cognitive' and
      'emotional' ToM scores, 2) qualitative analysis of errors brought about by
      'undermentalizing' or 'overmentalizing' strategies and 3) non-social inferencing
      as a control factor. RESULTS: Patients compared to controls scored significantly
      lower for 'cognitive' (F=9.417, df=1, p=0.003) but not for 'emotional' ToM.
      Bipolar patients showed significantly higher 'undermentalizing' (F=4.830, df=1,
      p=0.032) but not 'overmentalizing' scores. A significant correlation (controlled
      for age) between the number of (hypo)manic episodes and 'undermentalizing'
      (r=0.527, p=0.030) as well as 'emotional' ToM (r=-0.546, p=0.023) was observed.
      LIMITATIONS: Sample size did not allow for the analysis of medication effects.
      DISCUSSION: This is the first study of ToM in euthymic bipolar patients with a
      realistic video-based examination. Independently from basic cognitive
      dysfunctions, patients displayed a pronounced deficit in the cognitive domain of
      ToM with preserved emotional mentalizing abilities. The correlation with the
      number of manic episodes may indicate an increase of the deficit with disease
      progression. It can be assumed that social cognition reflects an important
      dimension of the persisting cognitive deficits in bipolar disorder with possible
      impact on disease outcome.

PMID- 19748681
TI  - Internet monitoring of suicide risk in the population.
AB  - BACKGROUND: Public health statistics are often released too late to affect
      reversible societal factors affecting suicide. Increasingly, internet search
      volume is used in epidemiology, but this method has not yet been applied to
      suicide. METHODS: Google internet search engine activity for suicide-related
      terms from the years 2004-2009 was measured and correlated to available suicide
      and intentional self-injury data from the Centers of Disease Control (CDC).
      RESULTS: Google search volumes correlated to CDC statistics for both suicide and
      self-injury, but in patterns that differed by age. Whereas internet search
      activity was negatively correlated to the suicide rate in the general population,
      it was positively correlated to both intentional self-injury and completed
      suicides among youth. CONCLUSIONS: Monitoring changes in search volumes on the
      internet may provide an early indicator of suicide risk within the population.
      Furthermore, youth may utilize the internet in ways that differ from the general
      population with respect to suicide.

PMID- 19748682
TI  - Placental blood leukocytes are functional and phenotypically different than
      peripheral leukocytes during human labor.
AB  - Rupture of the fetal membranes during human labor is associated with an
      inflammatory process localized to the maternal-fetal interface. There is evidence
      that specific leukocytes subsets are attracted to the choriodecidua, and that
      after homing they condition a local inflammatory microenvironment, possibly being
      directly involved in rupture of the membranes. In this study our aim was to
      compare the phenotypes and function of leukocytes located in the placental
      intervillous blood with peripheral leukocytes obtained before or after labor,
      including expression of modulators of inflammation in these cells. Flow cytometry
      revealed that the proportion of CD14(+) cells is increased in intervillous blood,
      suggesting the participation of monocytes/macrophages during labor. Real time qRT
      PCR showed that at term gestation and particularly during labor, placental blood
      leukocytes adopt a different expression pattern of pro-inflammatory cytokines
      than leukocytes in peripheral blood, including IL-1beta and IL-1RA. During labor,
      both placental and peripheral leukocytes increase their secretion of matrix
      metalloproteinase-9. Moreover, we showed that placental leukocytes respond
      differently than peripheral leukocytes to bacterial lipopolysaccharide, secreting
      differential amounts of TNF-alpha, IL-1beta and IL-6. Finally, a preliminary
      proteomic characterization of placental leukocytes revealed a significantly
      higher number of individual proteins than in peripheral leukocytes. Our results
      support the existence of selective subsets of leukocytes recruited to the
      maternal-fetal interface that may participate in the triggering of parturition.

PMID- 19748683
TI  - Identification of canine natural CD3-positive T cells expressing an invariant T
      cell receptor alpha chain.
AB  - A representative T-cell subset exclusively using an invariant TCRalpha chain
      (iTCRalpha) is natural killer T (NKT) cells which are becoming an emerging topic
      for cancer and immune disorder in humans and mice. However, NKT cells in dogs
      have not yet been identified. In this study, CD3(+) T-lymphocyte population
      reactive to alpha-galactosylceramide-loaded mouse CD1d (alpha-GalCer/CD1d) were
      identified with flow cytometric analysis in mononuclear cells from spleen, liver,
      and peripheral blood of a dog with percentages of 0.028%, 0.045%, and 0.004%,
      respectively. Using cDNA library synthesized from mRNAs of the alpha-GalCer/CD1d
      reactive CD3(+) lymphocytes in the spleen cells, molecular analysis of canine
      iTCRalpha was carried out. Consequently, Variable (Valpha) and Joining (Jalpha)
      regions of iTCRalpha cDNA were found to be homogeneous to both mouse Valpha14
      Jalpha281 and human Valpha24-JalphaQ. Characteristic features of iTCRalpha of NKT
      cells, such as the amino acid sequence of complementarity-determining region
      (CDR) 3 and extra cysteine residue, were well conserved among dogs, mice, and
      humans. In quantitative real-time PCR analysis, relative expression of the canine
      iTCRalpha mRNA in alpha-GalCer/CD1d reactive CD3(+) lymphocytes was 271-fold
      higher than that in CD3(+) lymphocytes unbound to alpha-GalCer/CD1d, indicating
      that the iTCRalpha mRNA was preferentially expressed in alpha-GalCer/CD1d
      reactive CD3(+) lymphocytes in the dog. Together, the results strongly suggested
      that alpha-GalCer/CD1d-binding CD3(+) T lymphocytes identified in this study
      could be considered to be canine NKT cells.

PMID- 19748684
TI  - Small but powerful: short peptide hormones and their role in autoimmune
      inflammation.
AB  - In the recent years, it has become increasingly clear that the immune response is
      also influenced by mediators which were first discovered as regulators in the
      nervous or also cardiovascular system. Here, small peptide hormones may play an
      important role. Kinins like bradykinins act on the endothelium and play a role
      for trafficking of lymphocytes over the blood-brain barrier. Neuropeptides like
      vasoactive intestinal peptide or neuropeptide Y also directly act on T cells and
      favour the differentiation of Th2 cells or regulatory T cell populations.
      Recently, the renin-angiotensin system (RAS) came into the focus of interest.
      Inhibition of the RAS at different levels may influence autoimmune responses and
      involve T cells as well as antigen-presenting cells, probably via different
      signalling pathways. Inhibitors of angiotensin converting enzyme and antagonists
      of the angiotensin 1 receptors are used in the treatment of hypertension, kidney
      disease or stroke by millions of people worldwide. These inexpensive and safe
      pharmaceuticals may also represent an interesting and innovative approach for the
      (combination) treatment of autoimmune diseases like multiple sclerosis.

PMID- 19748685
TI  - Notch: a new player in MS mechanisms.
AB  - Notch is a family of four transmembrane receptors (Notch1-4) that orchestrate
      differentiation of various cell types, tissues and organs. Recent studies have
      revealed that Notch, among other processes, regulates immune responses of
      peripheral T cells, controls oligodendrocyte maturation and myelination of axons
      and under inflammatory conditions affects activation of macrophages and
      microglia. Therefore, Notch signaling has been implicated in the differentiation
      and function of all cell types considered crucial for the development and
      clinical progression of multiple sclerosis (MS). Importantly,
      inflammatory/demyelinating lesions in MS and its animal model, autoimmune
      experimental encephalomyelitis (EAE), abundantly express Notch receptors, their
      ligands and downstream activation targets. In EAE, in vivo modulation of Notch
      signaling affects immune responses of myelin-reactive T cells, enhances tissue
      repair and reduces clinical severity of the disease. In this review, we present
      recent findings on how Notch signaling may affect function of both immune and
      glial cells, analyze data implicating the Notch pathway in MS and EAE, and
      discuss the therapeutic potential of manipulating Notch signaling in MS patients.

PMID- 19748686
TI  - Squelching glioblastoma stem cells by targeting REST for proteasomal degradation.
AB  - Glioblastoma brain tumors harbor a small population of cancer stem cells that are
      resistant to conventional chemotherapeutic and radiation treatments, and are
      believed responsible for tumor recurrence and mortality. The identification of
      the epigenetic molecular mechanisms that control self-renewal of glioblastoma
      stem cells will foster development of targeted therapeutic approaches. The
      transcriptional repressor REST, best known for its role in controlling cell fate
      decisions in neural progenitor cells, may also be crucial for cancer stem cell
      self-renewal. Two novel mechanisms for regulating the stability of REST have
      recently been revealed: these involve the telomere-binding protein TRF2 and the
      ubiquitin E3 ligase SCFbeta-TrCP. Reduced TRF2 binding to REST, and increased
      SCFbeta-TrCP activity, target REST for proteasomal degradation and thereby
      inhibit cancer stem cell proliferation. Neurological side effects of treatments
      that target REST and TRF2 may be less severe than conventional brain tumor
      treatments because postmitotic neurons do not express REST and have relatively
      stable telomeres.

PMID- 19748687
TI  - Changes in reproductive biomarkers in an endangered fish species (bonytail chub,
      Gila elegans) exposed to low levels of organic wastewater compounds in a
      controlled experiment.
AB  - In arid regions of the southwestern United States, municipal wastewater treatment
      plants commonly discharge treated effluent directly into streams that would
      otherwise be dry most of the year. A better understanding is needed of how
      effluent-dependent waters (EDWs) differ from more natural aquatic ecosystems and
      the ecological effect of low levels of environmentally persistent organic
      wastewater compounds (OWCs) with distance from the pollutant source. In a
      controlled experiment, we found 26 compounds common to municipal effluent in
      treatment raceways all at concentrations <1.0 microg/L. Male bonytail chub (Gila
      elegans) in tanks containing municipal effluent had significantly lower levels of
      11-ketotestosterone (p=0.021) yet higher levels of 17beta-estradiol (p=0.002) and
      vitellogenin (p=0.036) compared to control male fish. Female bonytail chub in
      treatment tanks had significantly lower concentrations of 17beta-estradiol than
      control females (p=0.001). The normally inverse relationship between primary male
      and female sex hormones, expected in un-impaired fish, was greatly decreased in
      treatment (r=0.00) versus control (r=-0.66) female fish. We found a similar, but
      not as significant, trend between treatment (r=-0.45) and control (r=-0.82) male
      fish. Measures of fish condition showed no significant differences between male
      or female fish housed in effluent or clean water. Inter-sex condition did not
      occur and testicular and ovarian cells appeared normal for the respective
      developmental stage and we observed no morphological alteration in fish. The
      population-level impacts of these findings are uncertain. Studies examining the
      long-term, generational and behavioral effects to aquatic organisms chronically
      exposed to low levels of OWC mixtures are needed.

PMID- 19748688
TI  - Profiles of functioning as predictors of mortality in old age: the advantage of a
      configurative approach.
AB  - This study proposes the concept of functioning profile, by which one's status is
      summarized across essential functioning domains, and validates its efficiency in
      predicting mortality. The study analyzed data of two cohorts of community
      dwelling Israelis aged 75 and over, nationally sampled in 1989 (N=1200) and 1999
      (N=421), respectively. Eight groups with differential profiles reflected higher
      versus lower levels of functioning in three domains: physical (activities of
      daily living), cognitive (Orientation-Memory-Concentration test=OMC) and
      affective (depressive symptoms). The analyses predicted mortality within 4 years,
      adjusting for sociodemographic and health variables. Relative to the optimal
      profile, most functioning profiles represented groups having elevated mortality
      risks of considerable consistency across cohorts. Physical functioning was the
      most predictive component in the profiles, but its combinations with cognitive
      and affective functioning produced unique contributions to mortality prediction.
      The study suggests that the functioning profile, representing a person-centered
      configurative approach (i.e., one that considers the person's combined standing
      on key factors), is a useful concept for delineating risk groups in late life and
      evaluating risk factors in predicting mortality.

PMID- 19748689
TI  - Detection and prognostic impact of renal dysfunction in patients with chronic
      heart failure and normal serum creatinine.
AB  - BACKGROUND: Accurate identification of renal dysfunction (RD) is crucial to risk
      stratification in chronic heart failure (CHF). Patients with CHF are at special
      risk of having RD despite normal serum creatinine (SCr), owing to a decreased Cr
      generation. At low levels of SCr, the equations estimating renal function are
      less accurate. This study was aimed to assess and compare the prognostic value of
      formulas estimating renal function in CHF patients with normal SCr. METHODS: We
      studied 462 patients with systolic CHF and normal SCr. Creatinine clearance was
      estimated by the Cockcroft-Gault (eCrCl) and glomerular filtration rate by the 4
      variable MDRD equation (eGFR); eCrCl normalized for body-surface area
      (eCrCl(BSA)) was calculated. The primary outcome was all-cause mortality at 2
      years. RESULTS: Seventy five patients died. At multivariate Cox regression
      analysis, only eCrCl(BSA) was significantly associated with mortality (p =
      0.006); eGFR (p = 0.24), eCrCl (p = 0.09) and BUN (p = 0.14) were not
      statistically significant predictors. The patients in the lowest eCrCl(BSA)
      quartile had an adjusted 2.1-fold (CI: 1.06-4.1) increased risk of mortality,
      compared with those in the referent quartile. Two-year survival was 70.4% in the
      lowest eCrCl(BSA) quartile and 89.7% in the referent quartile. Other independent
      predictors of mortality were ischemic etiology (RR: 2.16 [CI: 1.3-3.5], p =
      0.0017), NYHA III/IV class (RR: 2.45 [CI: 1.51-3.97], p = 0.0003), LVEF <0.25
      (RR: 3.38 [CI: 1.69-6.75], p = 0.014), and anemia (RR: 1.86 [CI: 1.16-2.99], p =
      0.009). CONCLUSIONS: A sizeable proportion of CHF patients have prognostically
      significant RD despite normal SCr. Such patients represent a high-risk subgroup
      and can more accurately be identified by the CG formula corrected for BSA than
      the MDRD.

PMID- 19748690
TI  - Age-dependent windows for cohort culling in BSE herds.
AB  - With the discovery of a BSE case in a herd, practice in Denmark prior to 2005 has
      been to cull any herd in its entirety, to avoid the risk of further cases.
      However, a growing dissatisfaction with this practice has led to a desire to be
      able to cull a minor fraction of a BSE herd only, while still removing the
      majority of the risk. One proposed method has been cohort culling. All animals in
      a certain age window around the age of the infected animal are culled, assuming
      that the BSE case and all other potential cases were infected at roughly the same
      time. This paper presents a method to characterize the animals in a BSE infected
      herd most at risk for developing BSE from the exposure that resulted in the index
      case. The results suggest that a +/-one-and-a-half year cohort cull would work
      well in Denmark for index BSE cases with an age of 6 years or less, but for older
      BSE cases the method is completely inadequate, making age-dependent windows a
      necessity. Formulas for calculating age-dependent windows are provided, and age
      dependent windows for a herd size corresponding to a herd size equal to the 85%
      percentile of the Danish herds are provided in graphical form. A case study with
      a 9-year-old index case is presented.

PMID- 19748691
TI  - The equine influenza epidemic in Australia: spatial and temporal descriptive
      analyses of a large propagating epidemic.
AB  - Australia experienced a large outbreak of equine influenza in August 2007. Nearly
      10000 premises were infected during the epidemic. We used spatial and temporal
      analytical techniques to describe the epidemic, to quantify important descriptors
      of the epidemic, and to generate hypotheses about how the epidemic progressed and
      which control tools assisted in eradication. Spatio-temporal epidemic curves
      revealed three phases in the epidemic: dispersal, local spread and disease fade
      out. Spatial dispersal of infection rapidly declined immediately after national
      movement restrictions were introduced. The epidemic peak had passed before
      emergency vaccination could have induced substantial immunity in the equine
      population. Thirty seven clusters of epidemiologically linked premises were
      delineated using an interpolated surface of date of onset of clinical signs,
      geographic data and location of infected premises. These clusters were analysed
      individually to parameterise key epidemic measures: cumulative incidence,
      incidence rate, effective reproduction rate, nearest neighbour spread distances,
      epidemic length and the number of infected premises. These measures were
      summarised by landscape (rural versus peri-urban location) and standardised by
      disease management zone. Compared to rural areas, peri-urban areas appeared to
      have a higher density of equine premises (4.66 premises km(-2) versus 0.80
      premises km(-2)), longer epidemics (95 days versus 87 days), more infected
      premises (393 versus 339) and a shorter spread distance (1.27 km versus 2.38 km).
      However, effective reproduction rates (2.04 versus 1.99), cumulative incidence
      (27.4 versus 26.9) and incidence rates (1.36 versus 1.54) were similar. The
      relative impact of vaccination and national movement restrictions in controlling
      this epidemic needs further investigation.

PMID- 19748692
TI  - Comparison of three radiotherapy modalities on biochemical control and overall
      survival for the treatment of prostate cancer: a systematic review.
AB  - BACKGROUND AND PURPOSE: For the radiation treatment of prostate cancer high dose
      should be delivered for optimal biochemical control. Treatment can be given by
      dose-escalated external beam radiotherapy (EBRT) or external beam radiotherapy
      combined with a radioactive seed implantation (EBSeeds) or high-dose rate (HDR)
      brachytherapy (EBTI). Differences in outcome between the modalities were assessed
      by a systematic review. MATERIALS AND METHODS: A systematic search was performed
      resulting in 40 articles to be used. Data were extracted on biochemical control
      and overall survival at 3, 5, and 8 years and other time points mentioned in the
      articles. Also known prognostic parameters were noted. Comparison of the
      modalities was done by a Weibull survival analysis and estimation of Hazard
      Ratio's (HR) was done with 95% confidence intervals (95% CIs). RESULTS: The HR
      for biochemical recurrence was 1.40 (95% CI 1.31-1.51) for EBRT relative to EBTI,
      and was 1.37 (95% CI 1.26-1.49) for EBSeeds relative to EBTI. The HR for overall
      survival was 1.50 (95% CI 1.29-1.73) for EBRT relative to EBTI, and was 2.33 (95%
      CI 2.04-2.66) for EBSeeds relative to EBTI. CONCLUSION: The combination of
      external beam radiotherapy and HDR brachytherapy results in a superior
      biochemical control and overall survival found in a systematic review on
      radiotherapy for prostate cancer.

PMID- 19748693
TI  - Target volume shape variation during irradiation of rectal cancer patients in
      supine position: comparison with prone position.
AB  - PURPOSE: To quantify the inter-fraction shape variation of the mesorectum for
      rectal cancer patients treated with 5 x 5 Gy in supine position and compare it to
      variation in prone position. METHODS AND MATERIALS: For 28 patients a planning CT
      (pCT) and five daily cone-beam-CT (CBCT) scans were acquired in supine position.
      The mesorectal part of the CTV (MesoRect) was delineated on all scans. The shape
      variation was quantified by the distance between the pCT- and the CBCT
      delineations and stored in surface maps after online setup correction. Data were
      analyzed for male and female patients separately and compared to prone data.
      RESULTS: A large range of systematic, 1-8 mm (1SD), and random, 1-5 mm, shape
      variation was found, comparable to prone patients. Random-shape variation was
      comparable for male and female patients, while systematic variation was 3 mm
      larger for female patients. CONCLUSIONS: Shape variation of the MesoRect is
      substantial, heterogeneous and different between male and female patients.
      Differences between supine and prone orientation, however, are small. Clinical
      margins should be differentiated in position along the cranio-caudal axis, in
      anterior-posterior direction and for gender. Margins should also be increased,
      even when online setup correction is used. Due to the small margin differences
      between prone and supine treatments, the setup choice should be determined on
      dose to the organs at risk.

PMID- 19748694
TI  - Postoperative morbidity and mortality in relation to leukocyte counts and time to
      surgery after short-course preoperative radiotherapy for rectal cancer.
AB  - BACKGROUND: Preoperative radiotherapy for rectal cancer decreases local
      recurrence rates, but increases postoperative complications. Impaired
      postoperative leukocyte reaction after preoperative short-course radiotherapy has
      been reported. The aim was to assess postoperative morbidity and mortality in
      relation to leukocyte reaction and the time interval between radiotherapy and
      surgery. MATERIALS AND METHODS: A retrospective analysis of patients included in
      the Stockholm I and II trials, randomising patients to surgery alone or to 5 x 5
      Gy with immediate surgery, identified pre- and postoperative leukocyte values for
      274 patients. RESULTS: In the surgery alone group (n=144), all but three patients
      (2%) reacted with leukocytosis (ratio post/preoperative >1.0) on day 1 and all
      but 9 (6%) on day 5. In the radiotherapy group (n=130), 40 (31%) became
      leukopenic (<4 x 10(9) cells/L) after radiotherapy, 29 (22%) reacted abnormally
      (leukopenia or ratio < or =1.0) on day 1 and 66 (51%) on day 5 (all p<0.001).
      Preoperative leukocyte counts did not influence postoperative morbidity, but a
      poor response on day 1 increased the risk of sepsis (p<0.05) and mortality (6/29
      (21%) vs. 6/101 (6%), p<0.05). An interval of 10 days or more between the start
      of radiotherapy and surgery also had an impact on mortality; 6/17 (35%) vs. 6/113
      (5%), p=0.001. In a logistic regression analysis, the time interval and age were
      independent predictors of mortality. CONCLUSIONS: Impaired postoperative
      leukocyte reaction is frequent after short-course radiotherapy and increases the
      risk of postoperative complications and death. A longer than recommended
      radiotherapy-surgery interval also appears to be detrimental for postoperative
      death, independently of leukocyte response.

PMID- 19748695
TI  - MRI-guided treatment-planning optimisation in intracavitary or combined
      intracavitary/interstitial PDR brachytherapy using tandem ovoid applicators in
      locally advanced cervical cancer.
AB  - PURPOSE: To study the impact of MRI-guided treatment planning on dose/volume
      parameters in pulsed dose rate (PDR) brachytherapy (BT) for cervical cancer.
      Additionally, we investigated the potential benefit of an
      intracavitary/interstitial (IC/IS) modification of the classical tandem ovoid
      applicator. MATERIAL AND METHODS: For 24 patients we compared Standard PDR BT
      plans, Scaled Standard plans and MRI-guided Optimised plans. The total EBRT/BT
      prescribed dose to Manchester point A or to 90% of the HR-CTV (D90 HR-CTV)
      expressed in EQD(2) was 80 Gy(alphabeta10) in 17 patients (Period I) and 84
      Gy(alphabeta10) in 7 patients (Period II). The constraints to 2 cm(3) of the OAR
      were 90 Gy(alphabeta3) for bladder and 75 Gy(alphabeta3) for rectum, sigmoid and
      bowel. Most cases were treated with a traditional intracavitary tandem ovoid
      applicator. In 6 patients we used a newly designed combined IC/IS modification
      for the second PDR fraction and investigated the benefit of the interstitial
      part. RESULTS: The average gain of MRI-guided optimisation expressed in D90 HR
      CTV was 4+/-9 Gy(alphabeta10) (p<0.001) and 10+/-7 Gy(alphabeta10) (p=0.003) in
      the two periods. The dose to 2 cm(3) of the OAR met the constraints. In the group
      that was treated with the combined IC/IS approach, we could increase the D90 HR
      CTV for the second PDR fraction with 5.4+/-4.2 Gy(alphabeta10) (p=0.005) and the
      D100 with 4.8+/-3.1 Gy(alphabeta10) (p=0.07). CONCLUSIONS: Three-dimensional MRI
      guided treatment planning and optimisation improves the DVH parameters compared
      to conventional planning strategies. Additional improvement can be achieved by
      using a combined IC/IS approach.

PMID- 19748696
TI  - In vitro evaluation of Lactobacillus plantarum DSMZ 12028 as a probiotic:
      emphasis on innate immunity.
AB  - In this study, we analyzed the probiotic potential of L. plantarum DSMZ 12028 in
      vitro using the pathogen E. coli K4 and a certified probiotic, L. paracasei F19,
      as controls. Adhesion to intestinal epithelial cells was evaluated using two cell
      lines, CaCo-2 and HT-29, through the plate dilution method. Moreover, the
      bacteria/epithelial dynamic interaction was continuously monitored using time
      lapse microscopy. Expression of the innate immunity receptors, the TLRs, was
      evaluated by semi-quantitative PCR on an epithelial/bacteria co-culture. Real
      time PCR was used to monitor expression of TLRs and cytokines in a monocytic cell
      line (THP-1) following bacterial exposure. The adherence of the strain to
      intestinal epithelial cells was comparable to that of the probiotic. Time-lapse
      experiments showed that E. coli K4 induced cell death while L. plantarum did not
      affect proliferation at a 10:1 bacteria/cell ratio. L. plantarum down-regulated
      TLR mRNAs with the exception of TLR2, while L. paracasei F19 and E. coli K4
      caused a significant (p<0.05) up-regulation of TLR2 and 4, respectively. To
      simulate the activation of underlying immune cells in the lamina propria, we
      analyzed the immunomodulation of L. plantarum on a monocytic cell line, THP-1.
      Proinflammatory cytokines, such as TNFalpha, were increased by the presence of
      bacteria. The pathogen E. coli K4 also induced a strong up-regulation of
      proinflammatory cytokines, such as IL8, IL1beta and IL23. No differences were
      observed between experimental groups for IFNgamma, IL-10 and IL12p40. Overall, L.
      plantarum DSMZ 12028 demonstrated probiotic traits, inducing a proinflammatory
      response just above the "threshold level", which could prevent an inflammatory
      outcome, while inducing a higher state of alertness in the defense system of the
      host intestinal epithelial cells.

PMID- 19748697
TI  - AI-2 signalling is induced by acidic shock in probiotic strains of Lactobacillus
      spp.
AB  - Survival and ability to respond to various environmental stresses such as low pH
      are important factors for lactobacilli for their function as probiotics. LuxS
      mediated quorum sensing mechanism, which is based on the production of universal
      signal molecule called autoinducer-2 (AI-2), regulates important physiological
      traits and a variety of adaptive processes in different bacteria. The aim of this
      study was to investigate the effect of acidic stress on LuxS-mediated quorum
      sensing (AI-2 signalling) in four probiotic strains of different Lactobacillus
      species. Initially, the production of AI-2-like molecule was investigated in four
      strains of Lactobacillus spp. at standard growth conditions using Vibrio harveyi
      bioluminescence assay. Species variation in AI-2 activity was observed. AI-2
      activity started at early-exponential growth phase and increased during the mid
      exponential phase concomitant with the reduction of pH, reaching maximum at late
      exponential phase (L. rhamnosus GG) or at stationary phase (L. salivarius UCC118,
      L. acidophilus NCFM and L. johnsonii NCC533). Acidic shock experiments were
      conducted on L. rhamnosus GG and L. acidophilus NCFM after exposure to different
      acidic shocks (pH 5.0, 4.0 and 3.0) and to pH 6.5 as control, measuring AI-2
      activity and transcription of the luxS gene. AI-2 activity increased by lowering
      the pH in a dose dependent manner and was negatively influenced by acid
      adaptation. In both species, the luxS gene was repressed after exposure to pH 6.5
      as control. However, after acidic shock (pH 4.0) a transient response of luxS
      gene was observed and the transcription augmented over time, reaching a maximum
      level and decreased subsequently. Acid adaptation of cells attenuated the
      transcription of this gene. Based on the observations done in the present study,
      the luxS gene appears to have a clear role in acidic stress response in probiotic
      lactobacilli. This might be important in the survival of these bacteria during
      the passage through the gastrointestinal tract, and further influence the cell-to
      cell communication among bacteria in the intestinal microbiota.

PMID- 19748698
TI  - Risk of recurrence in hepatitis B-related hepatocellular carcinoma: impact of
      viral load in late recurrence.

PMID- 19748699
TI  - Estimation of Japanese international financial assistance for HIV/AIDS control
      for 2003-2007: difficulties and limitations of data collection.
AB  - The purpose of this paper is to: (1) collect relevant data and estimate Japanese
      international financial assistance for HIV/AIDS control; (2) discuss the
      difficulties in collecting relevant data and the limitations of the collected
      data; and (3) conduct a comparative analysis on the estimated data with OECD and
      Kaiser Family Foundation aggregate data. The point is that we have
      comprehensively collected and estimated the data on Japanese international
      expenditures for HIV/AIDS control while there is no reliable data that is totally
      managed and published. In addition, we discuss the difficulties and limitations
      of data collection: unpublished data; insufficient data; inseparable data;
      problems of exchange rates; gaps between disbursement and commitment; and
      difference in year period among calendar, fiscal and organization-specific years.
      Furthermore, we show the risk of underestimating the Japanese international
      contribution to HIV/AIDS control on the basis of OECD and Kaiser data. In this
      respect, it is significant to comprehensively collect and estimate the data on
      Japanese international assistance for HIV/AIDS control. Finally, we derive the
      implication that it is crucial for a relevant international organization and/or
      individual countries to comprehensively collect and administer data for
      international cooperation in the development of health policies for HIV/AIDS.

PMID- 19748700
TI  - Behavioural reaction norms: animal personality meets individual plasticity.
AB  - Recent studies in the field of behavioural ecology have revealed intriguing
      variation in behaviour within single populations. Increasing evidence suggests
      that individual animals differ in their average level of behaviour displayed
      across a range of contexts (animal 'personality'), and in their responsiveness to
      environmental variation (plasticity), and that these phenomena can be considered
      complementary aspects of the individual phenotype. How should this complex
      variation be studied? Here, we outline how central ideas in behavioural ecology
      and quantitative genetics can be combined within a single framework based on the
      concept of 'behavioural reaction norms'. This integrative approach facilitates
      analysis of phenomena usually studied separately in terms of personality and
      plasticity, thereby enhancing understanding of their adaptive nature.

PMID- 19748701
TI  - Juvenile temporal arteritis.
AB  - Juvenile temporal arteritis (JTA) is a nongranulomatous inflammation of the
      temporal artery with fragmentation of the internal elastic lamina and no
      concurrent systemic manifestations. It is a rare clinicopathologic entity with
      fewer than 20 reported cases, most of which represent localized disease with no
      recurrence or systemic symptoms at follow-up of up to 2 years. Histopathologic
      features can include lymphoeosinophilic infiltrate and endothelial proliferation.
      As the histology may resemble angiolymphoid hyperplasia with eosinophilia or
      Kimura disease, whether JTA is a discrete localized disease or a manifestation of
      these systemic conditions has been debated. We present a case of a 36-year-old
      Jamaican woman with a painful forehead nodule that showed histologic features of
      JTA, including intimal hyperplasia, lymphoeosinophilic inflammation of the vessel
      wall, and disruption of the internal elastic lamina; distinctive signet ringlike
      cytomorphologic alterations of the endothelial cells were noted as well. The
      lesion also showed extensive subcutaneous lymphoeosinophilic infiltrates and
      neovascularization with extension into the underlying muscle consistent with
      angiolymphoid hyperplasia with eosinophilia or Kimura disease. As the connection
      between JTA and angiolymphoid hyperplasia with eosinophilia and Kimura disease is
      currently debated and most reported cases of JTA have had only brief follow-up,
      the long-term sequelae of JTA are not known and careful patient monitoring may be
      necessary.

PMID- 19748702
TI  - Effect of topical treatments on irritant hand dermatitis in health care workers.
AB  - BACKGROUND: Irritant contact dermatitis (ICD) from repetitive hand hygiene is the
      primary reason for compliance failure among health care workers (HCWs). Chronic
      ICD has implications for infection control because higher bacterial counts are
      associated with increased skin compromise. Guidelines recommend lotions/creams to
      lessen irritation. We evaluated the effects of 5 to 10 daily applications of a
      test cream (A, glove and chlorhexidine gluconate compatible) and current
      lotions/creams (B) compared with a control of normal skin care. METHODS: Outcomes
      were visual skin erythema and dryness, excess erythema (quantitative image
      analysis), and hydration among 80 HCWs in an intensive care unit. RESULTS:
      Knuckle dryness was lower for both treatments than the no treatment control (P <
      .02) after 2 weeks. Skin treated with A had lower knuckle erythema (P=.03) than B
      and control. HCWs using A had lower excess erythema (right) than B and control (P
      < .04). Excess erythema was lower for A and B versus control (P=.003).
      CONCLUSION: Reduction in erythema suggests that frequent use of cream A may
      mitigate the damaging effects of repetitive hand hygiene and allow the skin to
      recover. Intensive treatment of HCW ICD may be required to counteract the skin
      compromise and minimize the negative impact on infection control.

PMID- 19748703
TI  - Health care worker perceptions of hand hygiene practices and obstacles in a
      developing region.
AB  - A structured self-assessment questionnaire was distributed to 8 southern and
      eastern Mediterranean hospitals to identify perceived obstacles to hand hygiene
      (HH). An insufficient number of sinks and alcohol handrub stations was rated by
      the vast majority of respondents as the most critical impediment, whereas
      improved availability of HH products was deemed the key intervention to increase
      compliance. The least importance and relevance were given to HH auditing and
      collegial reminders. While initiatives to improve HH compliance clearly must
      address infrastructural inadequacies, sociocultural issues also need to be
      considered when transposing initiatives found to be successful in Western
      countries to less-developed regions, to ensure that campaigns are not compromised
      by perceptual undercurrents.

PMID- 19748704
TI  - Perceptions and attitudes of the professional staff concerning infection
      surveillance and control programs in Brazilian hospitals.
AB  - BACKGROUND: Several countries have conducted studies to assess the status of
      their infection control programs (ICP) with the objective of improving quality of
      infection control practices. METHODS: To assess the perceptions and attitudes of
      the health care workers (HCW) concerning ICP in Brazilian hospitals, we conducted
      a cross-sectional survey using a self-administered online questionnaire during a
      Web-based course (WBC) on infection control (IC) and antimicrobial resistance
      (AR). RESULTS: Of 6256 Brazilian HCW registered for the WBC, 1998 were members of
      infection control committees (ICC) and answered the survey. Eight hundred six
      (40.4%) respondents said that an ICP was established for more than 10 years in
      their institutions. Most professionals reported that their hospitals perform
      microbiologic surveillance targeted at epidemiologically important multidrug
      resistant organisms, but the majority underestimated the prevalence of AR.
      CONCLUSION: Our survey highlights important information about the perceptions and
      attitudes of ICC members that may be used to tailor key interventions for
      implementing effective ICP. It suggests, additionally, that, to achieve
      countrywide standardized IC mechanisms in a developing country, authorities
      should consider the social, cultural, and economical disparities between regions
      and identify specific regional needs to make available the resources required to
      minimize such disparities.

PMID- 19748705
TI  - Maturation of BRI2 generates a specific inhibitor that reduces APP processing at
      the plasma membrane and in endocytic vesicles.
AB  - Processing of the amyloid-beta (Abeta) precursor protein (APP) has been
      extensively studied since it leads to production of Abeta peptides. Toxic forms
      of Abeta aggregates are considered the cause of Alzheimer's disease (AD). On the
      other end, BRI2 is implicated in APP processing and Abeta production. We have
      investigated the precise mechanism by which BRI2 modulates APP cleavages and have
      found that BRI2 forms a mature BRI2 polypeptide that is transported to the plasma
      membrane and endosomes where it interacts with mature APP. Notably, immature
      forms of APP and BRI2 fail to interact. Mature BRI2 inhibits APP processing by
      alpha-, beta- and gamma-secretases on the plasma membrane and in endocytic
      compartments. Thus, BRI2 is a specific inhibitor that reduces secretases' access
      to APP in the intracellular compartments where APP is normally processed.

PMID- 19748706
TI  - [Virchow's node as the form of onset of squamous cell carcinoma of the pancreas].
AB  - Squamous carcinoma of the pancreas is a highly uncommon tumor. CASE REPORT: A 63
      year-old man was referred to the gastroenterology department because of
      hyporexia, cachexia and weight loss. A left supraclavicular node was noted. The
      computed tomography scan showed a tumor in the pancreatic body involving the
      celiac axis. Histological examination of the supraclavicular node and pancreatic
      mass revealed squamous cell carcinoma. CONCLUSIONS: The incidence and
      characteristics of this highly infrequent tumor, as well as new treatment
      indications, are reviewed.

PMID- 19748707
TI  - [Infections in the elderly patient].

PMID- 19748708
TI  - ["That flesh, pink and perishable": analysis of disease-free survival analysis in
      breast cancer in Gipuzkoa (Spain) in the presence of competing risks].
AB  - OBJECTIVE: To analyze time of disease-free survival and relative survival in
      women diagnosed with breast cancer in the province of Gipuzkoa within the context
      of competing risks by assessing differences between the direct use of the Kaplan
      Meier estimator and the multiple decrement method on the one hand, and relative
      survival on the other. METHODS: All registered breast cancer cases in Gipuzkoa in
      1995 and 1996 with stages other than stage IV were included. An 8-year follow-up
      for recurrence and a 10-year follow-up for survival were performed. Time of
      disease-free survival was studied by the multiple decrement model. Observed
      survival and survival corrected by the expected mortality in the population
      (relative survival) were also studied. RESULTS: Estimation of the probability of
      recurrence at 8 years with the multiple decrement method was 8.8% lower than that
      obtained with the Kaplan-Meier method. The difference between the observed and
      relative survival rates at 10 years was 10.8%. Both results show how, in this
      case, the Kaplan-Meier estimator overestimates both the probability of recurrence
      and that of mortality from the disease. CONCLUSIONS: Two issues are often
      overlooked when performing survival analyses: firstly, because of the lack of
      independence between survival time and censoring time, the results obtained by
      the Kaplan-Meier estimator are uninterpretable; secondly, it is an
      incontrovertible fact that one way or another, everyone causes failures. In this
      approach, survival analyses must take into account the probability of failure in
      the general population of reference. The results obtained in this study show that
      superficial use of the Kaplan Meier estimator overestimates both the probability
      of recurrence and that of mortality caused by the disease.

PMID- 19748709
TI  - Oligomeric formylpeptide activity on human neutrophils.
AB  - A series of oligomeric formylpeptides were synthesized by cross-linking the
      prototype fMLP using a Lys residue. They were then investigated for their ability
      to stimulate chemotaxis, superoxide anion production, and lytic enzyme release in
      human neutrophils. Although active in stimulating the different receptor
      isoforms, leading to the different biological responses, these analogues showed a
      lesser potency and affinity than the standard peptide. On the basis of the
      results reported here, we can hypothesise that: (i) the increased bulk of these
      molecules seems to hinder their correct positioning into the receptor pocket,
      thereby hindering favourable receptor interaction; and that: (ii) fMLP space
      positions do not seem to allow the ligand to increase biological responses.

PMID- 19748710
TI  - Prospective study of self-reported usual snacking and weight gain in a
      Mediterranean cohort: the SUN project.
AB  - BACKGROUND & AIMS: It has been hypothesized that snacking could be a major factor
      in the development of obesity. However, the relationship between snacking and the
      increment in body weight remains controversial. Moreover, longitudinal studies
      about this issue are scarce. Thus, our objective was to prospectively assess the
      relationship between snacking and weight gain and obesity in a middle-aged free
      living population. METHODS: Longitudinal prospective Spanish dynamic cohort
      (10,162 university graduates; mean age: 39 years) followed-up for an average of
      4.6 years. Dietary habits were ascertained through a validated 136-item food
      frequency questionnaire. Usual snackers were defined as those participants who
      answered affirmatively when asked in the baseline assessment if they usually eat
      between meals. Validated self-reported weight and body mass index were collected
      at baseline and during follow-up. RESULTS: After adjusting for potential
      confounders, self-reported between-meal snacking was significantly associated
      with a higher risk of substantial weight gain (> or =3kg/year; p<0.001;> or
      =5kg/year, p<0.001;> or =10% baseline weight, p<0.001). Among participants with a
      baseline body mass index lower than 30kg/m(2) (n: 9709) we observed 258 new cases
      of obesity. Usual snackers presented an adjusted 69% higher risk of becoming
      obese during follow-up (Hazard Ratio: 1.69; 95% confidence interval: 1.30-2.20).
      CONCLUSION: Our results support the hypothesis that self-reported between-meal
      snacking can be a potential risk factor for obesity.

PMID- 19748711
TI  - A survey of consultant members of the British Association of Oral and
      Maxillofacial Surgeons regarding bisphosphonate-induced osteonecrosis of the
      jaws.
AB  - The aims of this survey of consultants in the British Association of Oral and
      Maxillofacial Surgeons were threefold. Firstly, to estimate the number of
      patients screened for oral health before starting intravenous bisphosphonate
      medication, secondly, to indicate the use of antibiotics in patients on
      bisphosphonates who need routine extraction of a lower first molar tooth, and
      finally to estimate the number of new and currently managed cases of
      bisphosphonate-induced osteonecrosis of the jaw (BONJ) in the last year, and
      approximately how many of those currently being managed had healed. A
      questionnaire was mailed to 322 consultants working at 154 hospitals in the
      summer of 2008. There were responses from 184 consultants (57%) and from 111
      hospitals (72%). Screening patients before starting intravenous bisphosphonates
      was uncommon (15%). Almost all consultants would prescribe antibiotics for molar
      extraction and in about two-thirds this was both before and after extraction.
      Relatively few would stop bisphosphonates. Nearly two-thirds of consultants had
      seen new cases of BONJ from intravenous treatment in the last year, and a quarter
      had seen three or more. A similar proportion had patients on intravenous
      bisphosphonates under review for BONJ, and it was estimated that in a fifth of
      patients the lesion had healed. This survey indicates current practice among oral
      and maxillofacial surgeons in the UK. A national project for the registration of
      new patients will provide a stronger evidence base with respect to incidence,
      risk factors, and management of BONJ.

PMID- 19748712
TI  - Use of cone beam computed tomography in the management of glass injuries to the
      face.

PMID- 19748713
TI  - Ganglion cyst of the temporomandibular joint.
AB  - We describe a case of a ganglion cyst of the temporomandibular joint (TMJ) and
      review the literature of this rare entity. Because of the rarity of such cysts in
      the TMJ, an accurate diagnosis is not usually made preoperatively. Treatment is
      surgical but, if a diagnosis can be made, a period of conservative management is
      justified.

PMID- 19748714
TI  - Acute bilateral renal vein thrombosis.

PMID- 19748715
TI  - Home hemodialysis, daily hemodialysis, and nocturnal hemodialysis: Core
      Curriculum 2009.

PMID- 19748716
TI  - Transplant renal vein thrombosis: role of preoperative and intraoperative Doppler
      sonography.

PMID- 19748717
TI  - Change in vascular access and mortality in maintenance hemodialysis patients.
AB  - BACKGROUND: We hypothesized that a change from central venous catheters to a
      fistula or graft would improve short-term mortality risk in maintenance
      hemodialysis patients. DESIGN: Prospective observational study. SETTING &
      PARTICIPANTS: All maintenance in-center hemodialysis patients treated in
      Fresenius Medical Care, North America legacy facilities alive on January 1, 2007
      with baseline laboratory data from December 2006. PREDICTOR: Access type
      (fistula, catheter, or graft), determined on December 31, 2006, and monthly
      thereafter. Conversion from a catheter to a fistula or graft during the 4-month
      period from January 1 to April 30, 2007. OUTCOME: Mortality was tracked from May
      1, 2007, to December 31, 2007. Standard and time-dependent Cox models were used
      to determine hazard risks (HRs) of death with and without adjustment for case-mix
      and laboratory values. RESULTS: At baseline, 79,545 patients had 43% fistulas,
      29% catheters, and 27% grafts. Mean age was 62 +/- 15 years, 54% were men, 51%
      were white, and 53% had diabetes. Compared with fistulas, unadjusted HRs of death
      were higher for grafts (1.22) and catheters (1.76; P < 0.001). In adjusted
      models, overall risk for grafts was decreased to 1.05 (95% limits, 1.003-1.100; P
      < 0.05) and approached that for fistulas consistently across multiple strata.
      Compared with patients who continued using a catheter, those who converted to
      either a graft or fistula had an HR of 0.69, whereas those who converted from a
      graft or fistula to a catheter had increased HRs to 2.12 (both P < 0.001).
      Similar trends were observed in the subset of incident patients (vintage < 90
      days at study onset). LIMITATIONS: Observational design with residual confounding
      from unmeasured patient, facility, and treatment-related factors. CONCLUSIONS:
      Catheters have the worst associated mortality risk. Changing from a catheter to a
      fistula or graft is associated with significantly improved survival. The risk for
      grafts approached that of fistulas, providing an alternative to prolonged
      catheter exposure and potentially less hazardous "bridge" toward a fistula.

PMID- 19748718
TI  - Asymmetric learning transfer between imagined viewer- and object-rotations:
      evidence of a hierarchical organization of spatial reference frames.
AB  - Neural resources subserving spatial processing in either egocentric or
      allocentric reference frames are, at least partly, dissociated. However, it is
      unclear whether these two types of representations are independent or whether
      they interact. We investigated this question using a learning transfer paradigm.
      The experiment and material were designed so that they could be used in a
      clinical setting. Here, we tested healthy subjects in an imagined viewer-rotation
      task and an imagined object-rotation task. The order of the tasks was
      counterbalanced across subjects. The results showed that subjects who did the
      viewer-rotation task first had fewer errors and shorter latencies of response in
      the object-rotation task, whereas subjects who did the object-rotation task first
      had little if any advantage in the viewer-rotation task. In other words, the
      results revealed an asymmetric learning transfer between tasks, which suggests
      that spatial representations are hierarchically organized. Specifically, the
      results indicate that the viewer-rotation task engaged allocentric
      representations and egocentric representations, whereas the object-rotation task
      engaged only egocentric representations.

PMID- 19748719
TI  - [Pelvic reconstruction with a vertical rectus abdominis flap (VRAM): Flap
      ischemia caused by a bladder globe].

PMID- 19748720
TI  - [Gluteoplasty with intramuscular silicone cohesive gel implants: a retrospective
      study of 50 cases].
AB  - For a few years, surgery of the gluteus has become more and more popular. In this
      retrospective study of 50 cases over a period of five years, the author presents
      his results, using a personal technique of gluteoplasty with intramuscular
      implants. After a review of the different current surgical techniques and of the
      different types of gluteus, the author describes his own surgical strategy.

PMID- 19748721
TI  - [Lung cancer and COPD: a common combination].
AB  - BACKGROUND AND OBJECTIVE: To analyse frequency, characteristics and patient
      survival with lung cancer (LC) and COPD, comparing them with patients without
      COPD. MATERIAL AND METHODS: A retrospective study, of patients diagnosed by means
      of cytohistology. Survival was estimated by the Kaplan-Meier method. The
      statistical analysis was carried out using SPSS 15.0. RESULTS: A total of 996
      patients were diagnosed, 39.8% COPD. Mean age 70+/-9.19 years. GOLD stages: I
      18.2%, II 53.6%, III 24%, IV 4.2%. The histological types: squamous cell
      carcinoma 48.2%, adenocarcinoma 22%, small cell carcinoma 22.5%. Survival was
      longer in the COPD group. CONCLUSIONS: LC and COPD are combined in 39.8%.
      Squamous cell type is more frequent and survival was longer in the COPD group.

PMID- 19748722
TI  - Severe dysuria attributable to a solitary leiomyoma of the greater omentum.

PMID- 19748723
TI  - Risk factors for reproductive tract infections among married women in rural areas
      of Anhui Province, China.
AB  - OBJECTIVES: The goal of this study is to identify factors that contribute to
      reproductive tract infections (RTIs) among women in rural China, including
      prevalence, influence of sociodemographic characteristics, knowledge, hygienic
      behaviors and the history of childbearing, menstruation and abortion. STUDY
      DESIGN: A stratified cluster sample of 53,652 married women in rural Anhui
      Province of China completed an interviewer-administered standardized
      questionnaire, and underwent gynecological examination and laboratory
      investigation. RESULTS: RTIs were relatively common (30,939/58.1%) among our
      sample of 53,652 married women. The three most frequent RTIs in our samples were
      endocervicitis, bacterial vaginosis (BV) and trichomoniasis, with prevalences of
      41.7%, 12.0% and 4.5%, respectively. Multiple infections were prevalent among our
      sample. 20.4% (10,854) of our sample had two RTIs and 8.8% (4713) had at least
      three RTIs. Multivariate analysis showed that women's age, education, occupation,
      dysmenorrhea, number of deliveries, personal hygiene habit, menstrual cycle,
      menstruation, abortion, the interval between abortion and sexual intercourse
      afterwards, RTI knowledge and the frequency of sexual intercourse per month were
      all related to RTIs in our sample. CONCLUSIONS: Among married women in rural
      China, the prevalence of RTIs was high, indicating the need for health education.

PMID- 19748724
TI  - Molecular mechanisms of functional rescue mediated by P53 tumor suppressor
      mutations.
AB  - We have utilized both molecular dynamics simulations and solution biophysical
      measurements to investigate the rescue mechanism of mutation N235K, which plays a
      key role in the recently identified global suppressor motif of K235/Y239/R240 in
      the human p53 DNA-binding domain (DBD). Previous genetic analysis indicates that
      N235K alone rescues five out of six destabilized cancer mutants. However, the
      solution biophysical measurement shows that N235K generates only a slight
      increase to the stability of DBD, implying a rescue mechanism that is not a
      simple additive contribution to thermodynamic stability. Our molecular
      simulations show that the N235K substitution generates two non-native salt
      bridges with residues D186 and E198. We find that the nonnative salt bridges,
      D186-K235 and E198-K235, and a native salt bridge, E171-R249, are mutually
      exclusive, thus resulting in only a marginal increase in stability as compared to
      the wild type protein. When a destabilized V157F is paired with N235K, the native
      salt bridge E171-R249 is retained. In this context, the non-native salt bridges,
      D186-K235 and E198-K235, produce a net increase in stability as compared to V157F
      alone. A similar rescue mechanism may explain how N235K stabilize other highly
      unstable beta-sandwich cancer mutants.

PMID- 19748725
TI  - Metastatic renal cell carcinoma: recent advances in the targeted therapy era.
AB  - CONTEXT: The treatment of metastatic renal cell carcinoma (mRCC) has recently
      evolved from being predominantly cytokine based to being grounded in the use of
      targeted agents. OBJECTIVE: To analyse current evidence on the medical management
      of mRCC. EVIDENCE ACQUISITION: The PubMed and Medline databases were searched for
      articles published as of 15 July 2009. Only articles published in English were
      considered. The search terms were metastatic renal cell cancer, targeted therapy,
      and immunotherapy. Proceedings from the 2000-2009 conferences of the American
      Society of Clinical Oncology, the American Urological Association, and the
      European Association of Urology were also searched for relevant abstracts.
      EVIDENCE SYNTHESIS: Sunitinib has recently emerged as a front-line standard of
      care in mRCC. Temsirolimus is considered a first-line therapy for patients with
      poor risk features. Bevacizumab/interferon is likely to be the next U.S. Food and
      Drug Administration-approved first-line treatment. The use of sorafenib has moved
      toward second-line and later therapy. Everolimus was the first agent to show
      clinical benefit post-tyrosine kinase inhibitor failure in a phase 3 study and is
      considered the standard of care in this setting. Temsirolimus provided benefit to
      patients with non-clear-cell histology. In preliminary results, a favourable risk
      benefit ratio has been shown with pazopanib and axitinib as first- and second
      line treatment. Until combination therapy is clearly shown to be superior to
      monotherapy, it should be used in the context of a clinical trial. Deciding which
      is the best sequence to use in mRCC patients remains up to the best judgement of
      the treating physician. Cytoreductive nephrectomy in the presence of metastatic
      disease is often indicated as part of an integrated management strategy.
      CONCLUSIONS: Given considerable advances in understanding the biology of mRCC,
      several new drugs have recently been developed, offering an increasing number of
      treatment options. A treatment algorithm based on the best available evidence so
      far can be therefore postulated, though it continues to evolve as data from
      ongoing trials become available.

PMID- 19748726
TI  - Right-sided neglect influences the writing of Kanji: A case study.
AB  - Neglect is the failure to report, respond, or orient to novel or meaningful
      stimuli presented to the side opposite a brain lesion. Here we describe the case
      of a 73-year-old woman who experienced a writing deficit in the right-sided
      component of Kanji letters (morphograms) of the Japanese language. Magnetic
      resonance imaging of the brain showed an infarction in the left middle temporal
      and occipital gyrus. The patient wrote recognizable, well-formed but paragraphic
      Kanji letters in both spontaneous and dictated writing. Most letters are composed
      of two elements: "hen" (left) and "tsukuri" (right). Neographism in tsukuri was
      her most frequent error. When she was instructed to answer orally hen and
      tsukuri, she made more mistakes related to tsukuri than to hen. Unilateral
      spatial neglect in memory or imagery was reported. We concluded that unilaterally
      disrupted processing of internal representations affected the writing of Kanji
      letters in this patient.

PMID- 19748727
TI  - EDG3 and SHC3 on chromosome 9q22 are co-amplified in human ependymomas.
AB  - By qPCR we found that EDG3 and SHC3 were amplified in 60% of ependymomas but none
      in choroid plexus papillomas. In ependymomas EDG3 and SHC3 amplification
      increased Shc3 protein levels while EDG3 was less affected. Both proteins were co
      immunoprecipitated from ependymoma and Shc3 was tyrosine phosphorylated thus
      presumably active. We showed by digestion with N-glycosidase-F that EDG3 was
      glycosylated indicating that EDG3 protein was not retained in the endoplasmic
      reticulum. The co-immunoprecipitation of Shc3 and EDG3 proteins from ependymomas
      with amplification of SHC3 and EDG3 genes suggests that the two proteins co
      operate and are important for ependymomas in vivo.

PMID- 19748728
TI  - Adsorption of Cr(VI) from aqueous solution by hydrous zirconium oxide.
AB  - A type of ZrO(2).nH(2)O was synthesized and its Cr(VI) removal potential was
      investigated in this study. The kinetic study, adsorption isotherm, pH effect,
      thermodynamic study and desorption were examined in batch experiments. The
      kinetic process was described by a pseudo-second-order rate model very well. The
      Cr(VI) adsorption tended to increase with a decrease of pH. The adsorption data
      fitted well to the Langmuir model. The adsorption capacity increased from 61 to
      66 mg g(-1) when the temperature was increased from 298 to 338 K. The positive
      values of both Delta H degrees and DeltaS degrees suggest an endothermic reaction
      and increase in randomness at the solid-liquid interface during the adsorption.
      Delta G degrees values obtained were negative indicating a spontaneous adsorption
      process. The effective desorption of Cr(VI) on ZrO(2).nH(2)O could be achieved
      using distilled water at pH 12.

PMID- 19748729
TI  - Response surface modeling and optimization of chromium(VI) removal from aqueous
      solution using Tamarind wood activated carbon in batch process.
AB  - The present paper discusses response surface methodology (RSM) as an efficient
      approach for predictive model building and optimization of chromium adsorption on
      developed activated carbon. In this work the application of RSM is presented for
      optimizing the removal of Cr(VI) ions from aqua solutions using activated carbon
      as adsorbent. All experiments were performed according to statistical designs in
      order to develop the predictive regression models used for optimization. The
      optimization of adsorption of chromium on activated carbon was carried out to
      ensure a high adsorption efficiency at low adsorbent dose and high initial
      concentration of Cr(VI). While the goal of adsorption of chromium optimization
      was to improve adsorption conditions in batch process, i.e., to minimize the
      adsorbent dose and to increase the initial concentration of Cr(VI). In the
      adsorption experiments a laboratory developed Tamarind wood activated carbon made
      of chemical activation (zinc chloride) was used. A 2(4) full factorial central
      composite design experimental design was employed. Analysis of variance (ANOVA)
      showed a high coefficient of determination value (R(2)=0.928) and satisfactory
      prediction second-order regression model was derived. Maximum chromium removal
      efficiency was predicted and experimentally validated. The optimum adsorbent
      dose, temperature, initial concentration of Cr(VI) and initial pH of the Cr(VI)
      solution were found to be 4.3g/l, 32 degrees C, 20.15 mg/l and 5.41 respectively.
      Under optimal value of process parameters, high removal (>89%) was obtained for
      Cr(VI).

PMID- 19748730
TI  - Characterization of sodium dodecyl sulfate modified iron pillared montmorillonite
      and its application for the removal of aqueous Cu(II) and Co(II).
AB  - Anionic surfactant modified Fe-pillared montmorillonites were prepared by Fe
      hydrate solution and sodium dodecyl sulfate (SDS) solution. These organo-inorgano
      complex montmorillonites were divided into three types (CM1, CM2 and CM3)
      depending on different intercalation processes. X-ray diffraction spectra, the
      Fourier transform infrared (FTIR) spectra were used to analyze the structure of
      the raw and modified montmorillonites. X-ray photoelectron spectra of the samples
      have been studied to determine spectral characteristics to allow the
      identification of Fe(III) hydroxide. The specific surface area of the host
      montmorillonite (M0) is 73.2m(2)/g, while for the modified montmorillonites it is
      114.0m(2)/g, 117.2m(2)/g, and 115.8m(2)/g, respectively. The mesopore volumes of
      the montmorillonites decrease after modification. Ions of copper and cobalt were
      selected as adsorbates to evaluate the adsorption performance of each
      montmorillonite. The adsorption data was analyzed by both Freundlich and Langmuir
      isotherm models and the data was well fit by the Langmuir isotherm model. The
      adsorption was efficient and significantly influenced by metal speciation, metal
      concentration, contact time, and pH. Higher adsorption capacity of the modified
      montmorillonites were obtained at pH 5-6. The results of desorption indicated
      that the metal ions were covalently bound to the modified montmorillonites.

PMID- 19748731
TI  - Microwave induced catalytic degradation of crystal violet in nano-nickel dioxide
      suspensions.
AB  - Nickel oxide catalyst was obtained by precipitation-oxidation method with the
      assistance of microwave irradiation. The samples were characterized by X-ray
      diffraction, Raman spectrophotometer, Fourier transform infrared spectroscopy, X
      ray photoelectron spectroscopy, surface area and porosity analyzer. On the basis
      of the results, the as-prepared product was nano-NiO(2) with OH group and active
      oxygen. The catalytic activity of the as-prepared product might be attributed to
      its microwave absorbing property and the role of active oxygen, OH group under
      microwave irradiation. The microwave induced catalytic degradation process (MICD)
      with as-prepared product was further applied to degrade triphenylmethane dye
      crystal violet (CV). 97% of a 100 mg L(-1) sample of CV was rapidly degraded in 5
      min with the corresponding 81% TOC removal. The main intermediates were separated
      and identified by LC-ESI-MS and GC-MS techniques. The LC-ESI-MS analytical
      results demonstrated that a series of N-de-methylation products were obtained in
      a stepwise manner, namely mono-, di-, tri-, tetra-, penta-, and hexa-de
      methylated CV species. Nine organic acids with benzene ring and four low
      molecular acids were yielded with the assistance of GC-MS. The proposed
      degradation pathways were discussed in this study. The degradation processes
      might include N-de-methylation, destruction of conjugated structure and opening
      benzene ring. MICD, as a potential technique with wide application perspective,
      can be used to purify triphenylmethane dye wastewater with nanosized nickel
      dioxide.

PMID- 19748732
TI  - Effect of soil organic matter chemistry on sorption of trinitrotoluene and 2,4
      dinitrotoluene.
AB  - The sorption of organic contaminants in soil is mainly attributed to the soil
      organic matter (SOM) content. However, recent studies have highlighted the fact
      that it is not the total carbon content of the organic matter, but its chemical
      structure which have a profound effect on the sorption of organic contaminants.
      In the present study sorption of two nitroaromatic contaminants viz.
      trinitrotoluene (TNT) and 2,4-dinitrotoluene (2,4-DNT) was studied in different
      SOM fractions viz. a commercial humic acid, commercial lignin and humic acid and
      humin extracted from a compost. (13)C-DP/MAS NMR studies indicated that the
      structural composition of the organic carbon in different SOM fractions was
      different. The order of sorption of the nitroaromatics in the different sorbents
      was: humic acid-commercial>humic acid-compost>humin approximately lignin. Among
      the aliphatic and aromatic carbon fractions (representing bulk of SOM matrix),
      adsorption parameter K(f)(1/n) for nitroaromatics sorption correlated well with
      the aliphatic carbon (r=0.791 for TNT and 0.829 for 2,4-DNT) than the aromatic
      carbon (r=0.634 for TNT and r=0.616 for 2,4-DNT). However, among carbon
      containing functional groups, carbonyl carbon showed strong positive correlation
      with sorption of TNT (r=0.991) and 2,4-DNT (r=0.967) while O-alkyl carbon showed
      negative correlation (r=0.832 for TNT and r=0.828 for 2,4-DNT). The study
      indicates that aliphatic domains in the SOM significantly affect the non-specific
      sorption of both the nitroaromatic contaminants.

PMID- 19748733
TI  - Batch and column separation characteristics of copper-imprinted porous polymer
      micro-beads synthesized by a direct imprinting method.
AB  - Copper (II) ion-imprinted porous polymethacrylate micro-particles were prepared.
      Two functional monomers, methacrylic acid and vinyl pyridine, formed a complex
      with the template copper ion through ionic interactions. The self-assembled
      copper/monomer complex was polymerized in the presence of an ethylene glycol
      dimethacrylate cross-linker by a suspension method. After the imprinting sites
      were provided through removal of the template, the micro-porous particles, of
      approximate size 200 microm, were obtained for batch and column separation
      applications. The chemical structure and morphology of the Cu(II)-imprinted micro
      porous particles were analyzed using FTIR, SEM, and BET. The adsorption capacity
      and adsorption kinetics of the imprinted beads for the template Cu(II) ion were
      significantly affected by particle size, copper ion concentration, pH, and flow
      rate of the feed solution. The imprinted particles showed high selectivity for
      the copper ion over other metal ions such as Ni and Zn. The selectivity of the
      present imprinted polymers for the copper ion was at least 10 times as high as
      those from commercial sources.

PMID- 19748734
TI  - Influence of EDTA washing on the species and mobility of heavy metals residual in
      soils.
AB  - Aiming to estimate the potential risk of ethylenediaminetetraacetic acid (EDTA)
      enhanced soil washing, the heavy metal species and their mobility in the washed
      soil under different combinations were investigated by batch leaching tests and
      the sequential extraction procedure. Results demonstrate that the metal removal
      efficiency was rather low (less than 12%), partially due to the significant Ca
      dissolution and strong bonding between metals and the soil as well as the
      insufficient EDTA dosage. The washing combination of 0.0005 M EDTA and half-an
      hour washing can enhance the instant mobility of Ni, Zn and Pb possibly owing to
      the slow detachment of EDTA-destabilized metals. Metal fractionation also
      exhibits the corresponding increase in their labile exchangeable fractions.
      Therefore, a more concentrated EDTA solution for a longer duration often
      decreased their mobility. The increase in some fractions of a curtain metal
      implies the redistribution of this metal during the EDTA soil washing. The
      pathway of such a redistribution may vary for different metals, but the
      redistribution to organic matter is often a slow process, while that to
      carbonates or Fe/Mn oxides is a faster one and even may occur in a half hour
      washing with 0.0005 M EDTA solution. These redistribution processes may also
      increase the metal chemical availability. Therefore, we should prudently control
      the chelating reagent concentration and washing duration to finally minimize the
      mobility and availability of the remaining heavy metals when designing the soil
      washing for the remediation of metal-contaminated soils.

PMID- 19748735
TI  - Synergistic effects of hollow structure and surface fluorination on the
      photocatalytic activity of titania.
AB  - To study the synergistic effects of hollow structure and surface fluorination on
      the photoactivity of TiO(2), TiO(2) hollow microspheres were synthesized by a
      hydrolysis-precipitate method using sulfonated polystyrene (PS) as templates and
      tetrabutylorthotitanate (TBOT) as precursor, and then calcined at 500 degrees C
      for 2h. The calcined samples were characterized by X-ray diffraction, scanning
      electron microscopy, transmission electron microscopy and N(2) sorption.
      Photocatalytic activity was evaluated using reactive brilliant red X3B, an
      anionic organic dye, as a model pollutant in water. The results show that the
      photocatalytic activity of TiO(2) hollow microspheres is significantly higher
      than that of TiO(2) nanoparticles prepared in the same experimental conditions.
      At pH 7 and 3, the apparent rate constants of the former exceed that of the
      latter by a factor of 3.38 and 3.15, respectively. After surface fluorination at
      pH 3, the photoactivity of hollow microspheres and nanoparticles further
      increases for another 1.61 and 2.19 times, respectively. The synergistic effect
      of surface fluorination and hollow structure can also be used to prepare other
      highly efficient photocatalyst.

PMID- 19748736
TI  - Utilization of carbon derived from mustard oil cake (CMOC) for the removal of
      bivalent metal ions: effect of anionic surfactant on the removal and recovery.
AB  - Effect of sodium dodecyl sulfate (SDS) on the adsorption of Zn(II) and Ni(II) on
      CMOC was investigated. Addition of SDS favored the adsorption process. Adsorption
      process was found to be dependent on concentration, pH, dose, contact time and
      temperature. Thermodynamic studies showed that the process is endothermic and
      spontaneous. The spontaneity increases with increase in temperature. D-R isotherm
      suggests that the adsorption is chemical in nature. Kinetics studies showed
      better applicability of pseudo second order model. Reichenberg equation showed
      that pore diffusion was not only the rate determining step but some other process
      like film diffusion was also involved in the adsorption. These metals could be
      desorbed (75-80%) with 0.1M HCl as eluent.

PMID- 19748737
TI  - Carbon spheres/activated carbon composite materials with high Cr(VI) adsorption
      capacity prepared by a hydrothermal method.
AB  - Glucose and commercial activated carbon (AC) were used as starting materials to
      hydrothermally synthesize carbon spheres on the surface of AC, producing new
      carbon sphere-AC hybrid carbon materials. It was found that micrometer-sized
      carbon spheres, rich in oxygen-containing functional groups, can be effectively
      anchored to, and well-dispersed on, the surface and at the entrance to the
      macropores of AC. As the glucose concentration increased, the size and dispersion
      of carbon spheres changed, the porosity of the AC decreased, the number of oxygen
      containing functional groups increased, and C--OH gradually became the dominant
      functional group. The carbon composites that were obtained exhibited a remarkably
      enhanced adsorption capacity for Cr(VI) per unit mass and per unit surface area.
      The highest adsorption capacity per unit mass achieved was 0.4834 mmol g(-1),
      about 4 times that of unmodified AC. The abundant surface oxygen-containing
      functional groups and relatively well-developed pore structure were the main
      causes of the high specific adsorption capacity of the carbon sphere/AC
      composites.

PMID- 19748738
TI  - Formation of haloacetamides during chlorination of dissolved organic nitrogen
      aspartic acid.
AB  - The stability of haloacetamides (HAcAms) such as dichloroacetamide (DCAcAm) and
      trichloroacetamide (TCAcAm) was studied under different experimental conditions.
      The yield of HAcAms during aspartic acid (Asp) chlorination was measured at
      different molar ratio of chlorine atom to nitrogen atom (Cl/N), pH and dissolved
      organic carbon (DOC) mainly consisted of humic acid (HA) mixture. Ascorbic acid
      showed a better capacity to prevent the decay of DCAcAm and TCAcAm than the other
      two dechlorinating agents, thiosulfate and sodium sulfite. Lower Cl/N favored the
      DCAcAm formation, implying that breakpoint chlorination might minimize its
      generation. The pH decrease could lower the concentration of DCAcAm but favored
      dichloroacetonitrile (DCAN) formation. DCAcAm yield was sensitive to the DOC due
      to higher chlorine consumption caused by HA mixture. Two possible pathways of
      DCAcAm formation during Asp chlorination were proposed. Asp was an important
      precursor of DCAN, DCAcAm and dichloroacetic acid (DCAA), and thus removal of Asp
      before disinfection may be a method to prevent the formation of DCAcAm, DCAN and
      DCAA.

PMID- 19748739
TI  - Bertsche, et al., multidisciplinary pain management based on a computerized
      clinical decision support system in cancer pain patients.

PMID- 19748741
TI  - Effects of fipronil (active ingredient of Frontline) on salivary gland cells of
      Rhipicephalus sanguineus females (Latreille, 1806) (Acari: Ixodidae).
AB  - The present study analyzed the effects of the chemical compound fipronil, active
      ingredient of Frontline (acaricide and insecticide), on the salivary glands of
      unfed and semi-engorged female Rhipicephalus sanguineus tick. Unfed females were
      only exposed to the concentration of 1 ppm of fipronil, while semi-engorged
      females were treated with fipronil in three concentrations: 1 ppm, 5 ppm, and 10
      ppm (distilled water was used as control). The histological and histochemical
      results revealed significant changes caused by this compound in the morphology
      and physiology of the gland tissue of unfed and semi-engorged females. In unfed
      females, the morphological changes in type I acini were characterized by an
      increase in size and diameter of the lumen. These changes are probably associated
      with the excretory function, indicating that type I acini might be responsible
      for eliminating this xenobiotic from the system of the parasite. In semi-engorged
      females, fipronil did not interfere in the cell death, which in these individuals
      occurred by apoptosis. However, it accelerated salivary gland degeneration, as
      the extent of damage increased along with the concentrations of the product. Our
      results clearly showed that fipronil interferes with the process of engorgement
      in females that consequently is reflected in the reproductive process, decreasing
      or even halting egg laying, and resulting in less blood losses for the hosts and
      reducing the transmission of pathogens through these glands.

PMID- 19748740
TI  - Role of SIP30 in the development and maintenance of peripheral nerve injury
      induced neuropathic pain.
AB  - Using the chronic constriction injury (CCI) model of neuropathic pain, we
      profiled gene expression in the rat spinal cord, and identified SIP30 as a gene
      whose expression was elevated after CCI. SIP30 was previously shown to interact
      with SNAP25, but whose function was otherwise unknown. We now show that in the
      spinal cord, SIP30 was present in the dorsal horn laminae where the peripheral
      nociceptive inputs first synapse, co-localizing with nociception-related
      neuropeptides CGRP and substance P. With the onset of neuropathic pain after CCI
      surgery, SIP30 mRNA and protein levels increased in the ipsilateral side of the
      spinal cord, suggesting a potential association between SIP30 and neuropathic
      pain. When CCI-upregulated SIP30 was inhibited by intrathecal antisense
      oligonucleotide administration, neuropathic pain was attenuated. This neuropathic
      pain-reducing effect was observed both during neuropathic pain onset following
      CCI, and after neuropathic pain was fully established, implicating SIP30
      involvement in the development and maintenance phases of neuropathic pain. Using
      a secretion assay in PC12 cells, anti-SIP30 siRNA decreased the total pool of
      synaptic vesicles available for exocytosis, pointing to a potential function for
      SIP30. These results suggest a role of SIP30 in the development and maintenance
      of peripheral nerve injury-induced neuropathic pain.

PMID- 19748742
TI  - The epidemiology of patients with burn injuries admitted to Norwegian hospitals
      in 2007.
AB  - OBJECTIVES: To study the incidence and outcome of burns in Norway in 2007, and to
      establish estimates for effective length of stay, mortality and economical costs.
      METHODS: Data from the Norwegian Patient Registry on all patients discharged from
      all somatic hospitals in Norway in 2007 with main or subsidiary diagnosis of burn
      injury (ICD-10: T20-31) were collected. RESULTS: Seven hundred and twenty-six
      patients (65.0% male) with acute burns were admitted to Norwegian hospitals in
      2007, requiring 8157 in-hospital days and resulting in a mean length of
      hospitalization per burn case of 11.3 days (S.D. 15.2). The mean age of the
      patients was 26.9 years (S.D. 25.5), and the mortality was 2.1%. For children
      below 5 years of age the incidence of burns admitted to hospital was
      82.5/100,000/year. The annual total cost for in-hospital burn care exceeded 10.5
      million euros (2,200,000 euros/million inhabitants) CONCLUSION: Compared to
      similar data from Norway (1992) the rate of admission for burns in 2007
      (15.5/100,000/year) appeared as high as in 1992, whereas the mean length of stay
      was reduced by 26%. Children under the age of 5 had a seven times higher
      incidence compared the rest of the population.

PMID- 19748743
TI  - Monitoring risk: post marketing surveillance and signal detection.
AB  - The primary goal of postmarketing surveillance is to provide information for risk
      assessment of a drug. Drugs affecting the central nervous system form a unique
      group of products for surveillance because they are often misused, abused, and
      diverted. These medications include opioid analgesics, stimulants, sedative
      hypnotics, muscle relaxants, anticonvulsants and other drug classes. Their
      adverse events are difficult to monitor because the perpetrator often attempts to
      conceal the misuse, abuse and diversion of the product. A postmarketing
      surveillance system for prescription drugs of abuse in the U.S. should include
      product specific information that is accurate, immediately available,
      geographically specific and includes all areas of the country. Most producers of
      branded opioid analgesic products have created systems that measure abuse from
      multiple vantage points: criminal justice, treatment professionals, susceptible
      patient populations and acute health events. In the past, the U.S. government has
      not established similar requirements for the same products produced by generic
      manufacturers. However, the Food and Drug Administration Amendments Act of 2007
      includes generic opioid analgesic products by requiring that all products
      containing potent opioid drugs perform rigorous surveillance and risk management.
      While general risk management guidance has been developed by FDA, more specific
      analyses and guidance are needed to improve surveillance methodology for drugs
      which are misused, abused, diverted.

PMID- 19748744
TI  - EEG spectral phenotypes: heritability and association with marijuana and alcohol
      dependence in an American Indian community study.
AB  - Native Americans have some of the highest rates of marijuana and alcohol use and
      abuse, yet neurobiological measures associated with dependence on these
      substances in this population remain unknown. The present investigation evaluated
      the heritability of spectral characteristics of the electroencephalogram (EEG)
      and their correlation with marijuana and alcohol dependence in an American Indian
      community. Participants (n=626) were evaluated for marijuana (MJ) and alcohol
      (ALC) dependence, as well as other psychiatric disorders. EEGs were collected
      from six cortical sites and spectral power determined in five frequency bands
      (delta 1.0-4.0 Hz, theta 4.0-7.5 Hz, alpha 7.5-12.0 Hz, low beta 12.0-20.0 Hz and
      high beta/gamma 20-50 Hz). The estimated heritability (h(2)) of the EEG
      phenotypes was calculated using SOLAR, and ranged from 0.16 to 0.67. Stepwise
      linear regression was used to detect correlations between MJ and ALC dependence
      and the spectral characteristics of the EEG using a model that took into account:
      age, gender, Native American Heritage (NAH) and a lifetime diagnosis of
      antisocial personality and/or conduct disorder (ASPD/CD). Increases in spectral
      power in the delta frequency range, were significantly correlated with gender
      (p<0.001) and marijuana dependence (p<0.003). Gender, age, NAH and ASPD/CD were
      all significantly (p<0.001) correlated with theta, alpha and beta band power,
      whereas alcohol dependence (p<0.01), gender (p<0.001), and ASPD/CD (p<0.001) were
      all correlated with high beta/gamma band power. These data suggest that the
      traits of EEG delta and high beta/gamma activity are correlated with MJ
      dependence and alcohol dependence, respectively, in this community sample of
      Native Americans.

PMID- 19748745
TI  - Environmental conditions, political economy, and rates of injection drug use in
      large US metropolitan areas 1992-2002.
AB  - City-specific studies have suggested the quality of the local environment and
      economic circumstances are associated with greater risk of injection drug use
      (IDU). No studies have assessed the relation among the quality of the local
      environment, economic circumstances, and IDU over time across US metropolitan
      areas. Annual numbers of IDUs in the 88 largest US metropolitan statistical areas
      (MSAs) were estimated by extrapolating, adjusting, and allocating existing
      estimates using various data sources. Generalized estimating equations were used
      to assess the relation among the quality of the local environment, metropolitan
      political economy, and IDU prevalence using lagged models taking into account
      potential confounders. MSAs with a worse local environment (measured as a one
      standard deviation difference) had a greater risk of IDU (relative risk
      [RR]=1.03, 95% confidence interval [CI]: 1.01, 1.06); similarly, a one-percentage
      point worsening of the political economy for an MSA was associated with greater
      risk of IDU (RR=1.04-1.10). Final models stratified by region indicated
      heterogeneity of effect by region whereby the quality of the local environment
      was associated with IDU strongest in the South (RR=1.12, CI: 1.05, 1.12) followed
      by the West (RR=1.04, CI: 1.01, 1.07) and Midwest (RR=1.03, CI: 1.00, 1.06), and
      the metropolitan political economy was associated with IDU in the West (RR=1.03
      1.09) and Northeast (RR=1.04-1.12). Our results underscore the importance of
      sociopolitical factors as determinants of IDU in MSAs. Structural solutions
      targeted at improving environmental conditions and economic circumstances should
      be considered as drug use interventions.

PMID- 19748747
TI  - Zoonotic aspects of arenavirus infections.
AB  - To date, the International Committee for Taxonomy of Viruses recognizes that the
      family Arenaviridae contains a unique genus Arenavirus that includes 22 viral
      species. There are nine additional arenaviruses that either have been discovered
      recently, or which taxonomic status remains pending. Arenaviruses have been
      classified according to their antigenic properties into two groups, the Lassa
      Lymphocytic choriomeningitis (LCM) serocomplex and the Tacaribe serocomplex which
      has been further divided into four evolutionary lineages. Each arenavirus is more
      or less tightly associated with a mammal host. The distribution of the host
      dictates the distribution of the virus. Humans may become infected by
      arenaviruses through direct contact with infected rodents, including bites, or
      through inhalation of infectious rodent excreta and secreta. Lassa, Junin,
      Machupo, Guanarito, and Sabia viruses are known to cause a severe hemorrhagic
      fever, in western Africa, Argentina, Bolivia, Venezuela, and Brazil,
      respectively. Infection by LCM virus can result in acute central nervous system
      disease, congenital malformations, and infection in organ transplantation
      recipients. Detection of arenaviruses in their animal host can be achieved by
      virus isolation, and has recently taken advantage of PCR-based techniques. The
      approach based on consensus degenerate primers has shown efficient for both
      detection of known arenaviruses, and discovery of new arenaviruses.

PMID- 19748746
TI  - Screening for atypical suicide risk with person fit statistics among people
      presenting to alcohol and other drug treatment.
AB  - Symptoms of internalizing disorders (depression, anxiety, somatic, trauma) are
      the major risk factors for suicide. Atypical suicide risk is characterized by
      people with few or no symptoms of internalizing disorders. OBJECTIVE: In persons
      screened at intake to alcohol or other drug (AOD) treatment, this research
      examined whether person fit statistics would support an atypical subtype at high
      risk for suicide that did not present with typical depression and other
      internalizing disorders. METHODS: Symptom profiles of the prototypical, typical,
      and atypical persons, as defined using fit statistics, were tested on 7408
      persons entering AOD treatment using the Global Appraisal of Individual Needs
      (GAIN; Dennis et al., 2003a,b). RESULTS: Of those with suicide symptoms, the
      findings were as expected with the atypical group being higher on suicide and
      lower on symptoms of internalizing disorders. In addition, the atypical group was
      similar or lower on substance problems, symptoms of externalizing disorders, and
      crime and violence. CONCLUSIONS: Person fit statistics were useful in identifying
      persons with atypical suicide profiles and in enlightening aspects of existing
      theory concerning atypical suicidal ideation.

PMID- 19748748
TI  - The evidence base for neonatal surgery.
AB  - The practise of evidence based medicine means integrating the clinical expertise
      with the best available external clinical evidence from systematic research.
      There is a lack of supporting scientific evidence from rigorous trials in
      neonatal surgery. The indications for surgery and the type of operation performed
      in neonates are rarely supported by randomised controlled trials. As a
      consequence, the majority of the operations performed in neonates are supported
      by retrospective studies and surgeon preference. This review article is focussed
      on operations in neonates which are performed by general paediatric surgeons.
      Only a few randomised controlled trials have been performed in neonatal diseases
      such as congenital diaphragmatic hernia, necrotizing enterocolitis, pyloric
      stenosis and inguinal hernia. All of these trials have been based on
      collaboration between paediatric surgical units highlighting the importance of
      creating a network of centres that will promote multicentre prospective studies.

PMID- 19748749
TI  - Description of semen characteristics from six-banded armadillos (Euphractus
      sexcinctus) collected by electroejaculation.
AB  - The aim of this study is to describe the characteristics of the semen from six
      banded armadillos (Euphractus sexcinctus) collected by electroejaculation. Six
      mature males were physically restrained and electroejaculated twice for the
      collection of semen. Semen collected was immediately evaluated for appearance,
      volume, pH, sperm motility, vigor, morphology, percentage of live sperm and
      functional membrane integrity by light microscopy. Semen was obtained from all
      (100%) twelve attempts conducted for electroejaculation. Armadillos' semen had a
      white-translucent appearance, and great viscosity. Mean values obtained in
      analysis of the semen were: 353+/-86 microl for volume, 9 for pH, 45+/-14 x
      10(6)sperm/ml for concentration, 61+/-7% motile sperm with 2+/-0.2 for vigor,
      55+/-7% live sperm, 86+/-2% morphologic normal sperm, and 46+/-6% functional
      membrane integrity. In conclusion, semen from six-banded armadillos can be
      efficiently obtained by electroejaculation. The characteristics of semen
      collected by electroejaculation in six-banded armadillos provide background
      information that may be useful for assisted breeding programs in the members of
      the Xenarthra family.

PMID- 19748750
TI  - Ability of Catalonian donkey sperm to penetrate zona pellucida-free bovine
      oocytes matured in vitro.
AB  - An experiment was designed to study the interaction between fresh/frozen-thawed
      donkey spermatozoa and zona pellucida (ZP)-free bovine oocytes in an attempt to
      develop a model for assessing cryopreserved Catalonian donkey sperm function.
      Semen from five donkeys was collected using an artificial vagina. Sperm motility
      and viability were immediately assessed and the semen sample cryopreserved. Sperm
      viability and motility were then reassessed immediately after thawing. The motion
      characteristics of the fresh and frozen-thawed spermatozoa were determined using
      a computer-assisted sperm analysis system. In vitro-matured cow oocytes were
      inseminated with different percent live donkey sperm (high (>60%) or low (<40%)
      viability donkey sperm). After 18h of co-incubation, the oocytes were fixed,
      stained with 4',6-diamidino-2-phenylindole (DAPI) and examined for sperm
      penetration, the number of penetrated spermatozoa per oocyte, and male pronucleus
      formation. Frozen-thawed spermatozoa from high viability semen showed
      significantly lower VCL, VAP and mean ALH values than did high viability fresh
      spermatozoa. In contrast, frozen-thawed spermatozoa of low viability had
      significantly higher velocity values than fresh spermatozoa of low viability. A
      significant positive correlation (P<0.01) was detected between percentage
      fertilization and viability (r=0.84), and between percentage fertilization and
      certain CASA parameters (VAP, r=0.56; VCL, r=0.61 and mean ALH, r=0.68). Fresh or
      frozen-thawed high viability spermatozoa penetrated 90.1% and 85.4% of bovine
      oocytes respectively. Lower rates of penetration were observed for fresh and
      frozen-thawed low viability spermatozoa (34% and 22.5% respectively). The donkey
      spermatozoa were able to fuse with the oolema and even to decondense and form the
      male pronucleus (85-94%). Larger numbers of penetrated spermatozoa per oocyte
      were recorded when high viability sperm samples were used, whether fresh (3.02
      vs. 1.12 for low viability sperm) or frozen-thawed (3.41 vs. 1.47). Consequently,
      low viability sperm samples showed higher percentages of monospermic penetration
      (91.17% and 61.97% for fresh and frozen-thawed sperm samples respectively). These
      findings suggest that bovine oocytes provide a useful model for assessing the
      penetration potential of frozen-thawed donkey sperm.

PMID- 19748751
TI  - [Right upper quadrant abdominal pain and fever. Genetic phospholipid deficiency].
AB  - A 35-year-old woman is referred for right upper quadrant abdominal pain and
      fever. She had a cholecystectomy for gallstones 4 years previously. An aunt has
      also had a cholecystectomy. Abdominal ultrasound examination shows numerous
      hyperechoic foci within the liver and some "comet tail" artifacts. Because of her
      age (less than 40), the recurrence of biliary symptoms after cholecystectomy, her
      family history and the intrahepatic hyperechoic foci, the diagnosis of low
      phospholipid-associated cholelithiasis (LPAC) syndrome is suspected and confirmed
      by the demonstration of a point mutation of the ABCB4 gene. Therapy by
      ursodeoxycholic acid (AUDC) is started. Symptoms improve and they disappear
      completely within a few weeks. The cause, pathophysiology, diagnosis and
      treatment are reviewed.

PMID- 19748752
TI  - The diagnostic value of diffusion-weighted magnetic resonance imaging in soft
      tissue abscesses.
AB  - PURPOSE: To study the diagnostic value of diffusion-weighted imaging (DWI) in
      soft tissue abscesses. MATERIALS AND METHODS: Fifty patients were included in
      this study who were thought to have soft tissue abscess or cystic lesion as a
      result of clinical and radiological examinations. Localisations of the lesions
      were: 1 periorbital, 3 breast, 14 intraabdominal, and 32 intramuscular lesions.
      After other radiological examinations, DWI was performed. The signal intensity
      values of the lesions were evaluated qualitatively according to the
      hyperintensity on b-1000 DWI, using 1.5 T MR system. All of the lesions were
      aspirated after DWI, and detection of pus in the aspiration material was accepted
      as gold standard for the diagnosis of abscess. RESULTS: In 38 of the 50 patients,
      hyperintensity was obtained on diffusion-weighted images. False-positive results
      were maintained in 2 of these patients, and true-positive results were maintained
      in 36 of them. In 11 of the 50 patients, hypointensity was visualised on
      diffusion-weighted images. False-negative results were maintained in 3 of these
      patients, and true-negative results were maintained in 8 of them. An abscess
      which was seen on post-contrast conventional MRI could not be seen on DWI, and
      this was regarded as false-negative. CONCLUSION: The sensitivity and specificity
      of diffusion-weighted images for detecting soft tissue abscesses were found to be
      92% and 80%, respectively. DWI has a high diagnostic value in soft tissue
      abscesses, and is an important imaging modality that may be used for the
      differentiation of cysts and abscesses.

PMID- 19748753
TI  - Proposal of Xanthomonas translucens pv. pistaciae pv. nov., pathogenic to
      pistachio (Pistacia vera).
AB  - Strains of Xanthomonas translucens have caused dieback in the Australian
      pistachio industry for the last 15 years. Such pathogenicity to a dicotyledonous
      woody host contrasts with that of other pathovars of X. translucens, which are
      characterized by their pathogenicity to monocotyledonous plant families. Further
      investigations, using DNA-DNA hybridization, gyrB gene sequencing and integron
      screening, were conducted to confirm the taxonomic status of the X. translucens
      pathogenic to pistachio. DNA-DNA hybridization provided a clear classification,
      at the species level, of the pistachio pathogen as a X. translucens. In the gyrB
      based phylogeny, strains of the pistachio pathogen clustered among the X.
      translucens pathovars as two distinct lineages. Integron screening revealed that
      the cassette arrays of strains of the pistachio pathogen were different from
      those of other Xanthomonas species, and again distinguished two groups. Together
      with previously reported pathogenicity data, these results confirm that the
      pistachio pathogen is a new pathovar of X. translucens and allow hypotheses about
      its origin. The proposed name is Xanthomonas translucens pv. pistaciae pv. nov.

PMID- 19748754
TI  - Rapid separation of desloratadine and related compounds in solid pharmaceutical
      formulation using gradient ion-pair chromatography.
AB  - We reported the development of an ion-pair chromatographic method to separate
      desloratadine and all known related compounds in Clarinex Tablets, which use
      desloratadine as active pharmaceutical ingredient (API). For the first time,
      baseline separation for desloratadine and all known related compounds was
      achieved by utilizing a YMC-Pack Pro C(18) column (150 mm x 4.6 mm I.D., 3 microm
      particle size, 120A pore size) and a gradient elution method. The mobile phase A
      contains 3 mM sodium dodecylsulfate (SDS), 15 mM sodium citrate buffer at pH 6.2,
      and 40 mM sodium sulfate, while the mobile phase B is acetonitrile. Chromsword,
      an artificial intelligence method development tool, was used to optimize several
      key chromatographic parameters simultaneously including buffer pH/solvent
      strength, and temperature/gradient profile. The resolution of desloratadine and
      desloratadine 3,4-dehydropiperidine derivative, one of the critical pairs was
      improved by adding 40 mM sodium sulfate. Ultraviolet detection at 267 nm was used
      to achieve the detection for desloratadine and all compounds. This method has
      been successfully validated according to ICH guidelines in terms of linearity,
      accuracy, quantitation limit/detection limit, precision, specificity and
      robustness. It could be used as a stability indicating method for desloratadine
      drug substances or drug products that use desloratadine as active pharmaceutical
      ingredient.

PMID- 19748755
TI  - Suitability of a liquid chromatography assay of neomycin sulfate to replace the
      microbiological assay for neomycin in USP Monographs.
AB  - The current USP National Formulary contains 65 Monographs for drug formulations
      containing neomycin. All 65 Monographs prescribe a bioassay for neomycin assay.
      This bioassay, based on cell culture, is labor intensive, has poor precision, and
      cannot be adapted for purity or identification. High-performance anion-exchange
      chromatography with integrated pulsed amperometric detection (HPAE-IPAD), a
      liquid chromatography technique, has been shown to be suitable for neomycin
      purity analysis and neomycin assay of an over-the-counter first aid cream (Hanko
      and Rohrer [17]). Here we propose that an HPAE-IPAD assay can replace the
      bioassay in the 65 neomycin-containing Monographs. We applied the HPAE-IPAD assay
      to four neomycin-containing drug products representing the four classes of
      formulations found in the 65 Monographs, liquid, solid, suspension, and cream.
      Each drug was analyzed with two chromatography systems, and on 3 separate days.
      For all products, HPAE-IPAD measurements were precise and accurate with respect
      to the label concentrations. There was also high accuracy for spike recovery of
      neomycin from the four drug products throughout 70-150% of the labeled
      concentration. These results suggest that an HPAE-IPAD assay would be an accurate
      assay for neomycin, and would be faster and more precise than the current
      bioassay.

PMID- 19748756
TI  - Characterization of the receptors for chicken GHRH and GHRH-related peptides:
      identification of a novel receptor for GHRH and the receptor for GHRH-LP (PRP).
AB  - Growth hormone-releasing hormone and its structurally related peptides, GHRH-like
      peptide (GHRH-LP) (also called PRP), peptide histidine-isoleucine (PHI),
      vasoactive intestinal polypeptide (VIP), and pituitary adenylate cyclase
      activating polypeptide (PACAP), have been reported to play important
      physiological roles in pituitary and extrapituitary tissues of vertebrates;
      however, little is known about the identity of these GHRH-related peptide
      receptors in birds. In this study, 6 receptors for GHRH and GHRH-related peptides
      (cGHRHR(1), cGHRHR(2), cGHRH-LPR, cPAC(1), cVPAC(1), and cVPAC(2)) were cloned
      from chicken brain or pituitary, and their functionalities were examined in
      Chinese hamster ovary (CHO) cells using a pGL3-CRE-luciferase reporter system.
      Results showed that: (1) all receptors are G protein-coupled receptors
      functionally coupled to the intracellular PKA signaling pathway; (2) 2 GHRH
      receptors (cGHRHR(1) and cGHRHR(2)) were identified, and both receptors could be
      potently activated by cGHRH; (3) cGHRH-LP could activate its specific receptor
      cGHRH-LPR (cPRP-R), and it also activated cGHRHR(1) and cGHRHR(2); and (4) PACAP
      could potently activate its receptors cPAC(1), cVPAC(1) and cVPAC(2); however,
      cVPAC(1) and cVPAC(2) could also be effectively activated by cVIP and tPHI,
      indicating that they can serve as VIP receptors and potential PHI receptors.
      Using a reverse transcription polymerase chain reaction assay, we further
      examined the mRNA expression of these receptors in adult chicken tissues. The
      expressions of cGHRHR(1), cGHRHR(2), and cGHRH-LPR are restricted mainly to the
      pituitary and/or brain, whereas cPAC(1), cVPAC(1), and cVPAC(2) are expressed in
      most of the tissues examined. Collectively, our study identified the receptors
      for chicken GHRH and GHRH-related peptides, including a novel GHRH receptor
      (cGHRHR(2)), and established a basis to elucidate the roles of these peptides in
      target tissues.

PMID- 19748757
TI  - Effects of GnRH treatment on initiation of pulses of LH, LH release, and
      subsequent concentrations of progesterone.
AB  - Progesterone is essential for establishment and maintenance of pregnancy. One
      proposed method to increase progesterone is administering GnRH at insemination.
      However, this method has resulted in conflicting results. Therefore, 2
      experiments were conducted to evaluate how administering GnRH at insemination
      affected pulses of luteinizing hormone (LH) and subsequent progesterone. In
      Experiment 1, cows were allotted to 2 treatments: (1) GnRH (100 microg) given
      approximately 12h after initiation of estrus (n=5); and (2) Control (n=5). Blood
      samples were collected at 15-min intervals for 6h at 12 (blood sampling period
      1), 26 (blood sampling period 2), 40 (blood sampling period 3), 54 (blood
      sampling period 4), and 68 (blood sampling period 5) h after onset of estrus.
      Daily blood samples were collected for 17 d. In Experiment 2, cows were allotted
      into 2 treatments: GnRH administered 10 to 11h (n=10) or 14 to 15 h (n=10) after
      onset of estrus. Daily blood samples were collected for 17 d. Cows treated with
      GnRH tended (P<or=0.075) to have greater LH release during blood sampling period
      1, tended (P=0.095) to have fewer pulses during blood sampling period 2, tended
      (P=0.067) to have greater concentrations of progesterone, and had an earlier
      (P=0.05) increase in progesterone than control cows. Cows treated with GnRH 10 to
      11h after onset of estrus had greater (P=0.01) progesterone and an earlier
      (P=0.04) increase in progesterone than cows treated 14 to 15 h. In conclusion,
      timing of GnRH treatment following onset of estrus influenced pulses of LH and
      subsequent progesterone.

PMID- 19748758
TI  - Effect of citrus pectin on malignant cell proliferation.
AB  - The effect of citrus pectin (CP) on the proliferative capacity of four malignant
      cell lines was examined. Various dose of CP inhibited the proliferation of two
      colon carcinoma and an erythroleukemia cell lines. Raji cells were not affected
      at all. The three lines affected by CP are known to express galectins which are
      pivotal for cell growth and metastasis, while Raji cells, whose proliferation was
      not affected by CP, are deficient of this betagalactoside. It is possible that
      the antiproliferative effect of CP on the malignant cells may be due at least in
      part to its ability to inhibit galectin expression.

PMID- 19748759
TI  - Tamoxifen epigenetically modulates CXCL12 expression in MCF-7 breast cancer
      cells.
AB  - The CXCL12 chemokine binds to the CXCR4 receptor and contributes to survival,
      proliferation, and migration of malignant cells. Recent reports indicate that
      breast cancer cells lacking expression of CXCL12 but exhibiting CXCR4 can
      metastasize to target organs that secrete CXCL12. We observed that Tamoxifen
      (Tam), similarly to 5-dAzaC, results in significantly increased levels of CXCL12
      transcript and protein in MCF-7 breast cancer cells. Bisulfite sequencing
      suggests that Tam, similarly to 5-dAzaC, may increase CXCL12 expression via
      reduction in methylation of cytosine in the cytosine-guanosine (CpG) dinucleotide
      island of the CXCL12 promoter of MCF-7 cells. Our results, together with findings
      of other researches, may suggest that Tam epigenetically activates CXCL12
      expression in breast cancer cells and can make these cells less susceptible to
      attraction by exogenous CXCL12 to metastasis sites.

PMID- 19748760
TI  - Assessment of symptoms reported by 10- to 18-year-old cancer patients in Taiwan.
AB  - The purposes of this study were 1) to assess and describe the occurrence,
      frequency, severity, and distress of symptoms reported by Taiwanese pediatric
      cancer patients who were between 10 and 18 years of age, and 2) to use
      statistical analysis to determine whether the multiple dimensions (i.e.,
      frequency, severity, or distress) of the Memorial Symptom Assessment Scale (MSAS)
      10-18 alone can provide sufficient useful information for the assessment of
      symptoms that patients report as distressing. A total of 144 Taiwanese pediatric
      cancer patients and their mothers participated in this cross-sectional study. The
      frequency of symptoms for all patients ranged from 52% for "lack of energy" to
      10% for "feeling nervous." The most common symptoms (occurrence >40%) were "lack
      of energy," "lack of appetite," "feeling drowsy," "sweating," "worrying,"
      "nausea," "dry mouth," "pain," and "lack of concentration." Patients in the "on
      treatment group" had more distressing symptoms than those in the "off-treatment
      group." The severity and distress subscales did provide the most information for
      symptom assessment and were the two best subscales to represent the impact of
      symptoms on quality of life, fatigue, and internalizing behaviors. The findings
      of this study suggest that revising the current format of the MSAS 10-18 into
      three separate instruments (one for each of the subscales) might provide more
      accurate data for assessments. Such a modification would change the scoring
      system and provide for more accurate data analysis.

PMID- 19748761
TI  - Randomized controlled pilot study of neuromuscular electrical stimulation of the
      quadriceps in patients with non-small cell lung cancer.
AB  - Patients with lung cancer experience muscle wasting and weakness. Therapeutic
      exercise may be beneficial but is not always practical. An alternative approach
      may be neuromuscular electrical stimulation (NMES) of the quadriceps muscles, but
      this has not been formally examined in patients with cancer. Thus, we have
      undertaken this pilot study to assess feasibility and inform the design of future
      studies. Sixteen patients were randomized to receive usual care (control group)
      or usual care plus NMES for four weeks. NMES consisted of daily stimulation to
      both thighs for up to 30minutes (frequency 50Hz, "on" cycle 11%-25%). Adherence
      was assessed by a self-report diary and a semistructured evaluation form.
      Quadriceps muscle strength, exercise endurance, and free-living physical activity
      were assessed using a Cybex NORM dynamometer, an endurance shuttle walk test, and
      an ActivPAL accelerometer (mean daily step count), respectively. Changes in
      outcome from baseline were compared between groups by mean differences and their
      95% confidence intervals using independent t-test (P=0.05). Median (range)
      adherence to the program was 80% (69%-100%). All patients found the NMES device
      easy to use. Changes in outcome favored the NMES group, with mean differences of
      9.4 Nm (21%) in quadriceps muscle strength, 768 steps (15%) in free-living
      activity, and 138 m (8%) in exercise endurance, but none of the differences were
      statistically significant. In conclusion, NMES warrants further study in patients
      with lung cancer.

PMID- 19748762
TI  - Carotid stent fracture with recurrent high-grade stenosis.
AB  - Stent fracture is a rare complication after carotid angioplasty and stenting.
      Patient anatomy, stent design, and external forces may all be contributing risk
      factors. Treatment options include continued observation or reintervention by
      both endovascular and open techniques since patients are typically asymptomatic.
      We present a case of a 66-year-old male with carotid stent fracture who developed
      recurrent, high-grade, asymptomatic carotid artery stenosis that was treated with
      repeat carotid angioplasty and stenting.

PMID- 19748763
TI  - Neoadjuvant aortic endografting.
AB  - The advent and success of endovascular repair of abdominal aneurysms led to the
      development of catheter-based techniques to treat thoracic aortic pathology. Such
      diseases, including thoracic aortic aneurysms, acute and chronic type B
      dissections, penetrating aortic ulcers, and traumatic aortic transection,
      challenge surgeons to perform complex open operative repairs in high-risk
      patients. The minimally invasive nature of thoracic endografting provides an
      attractive alternative therapy. We present two cases of covered stent grafts
      deployed in the thoracic aorta to perform resection of the aortic wall
      infiltrated by malignancy in order to avoid a major vascular intervention and a
      traditional vascular graft interposition. This may become a potential new utility
      for aortic endografts.

PMID- 19748764
TI  - Redo surgery or carotid stenting for restenosis after carotid endarterectomy:
      results of two different treatment strategies.
AB  - BACKGROUND: We evaluated retrospectively early and midterm results of
      conventional redo surgery and carotid stent-assisted angioplasty (CAS) in the
      treatment of carotis restenosis (CR) after carotid endarterectomy (CEA). METHODS:
      From January 1989 to April 2007, 79 consecutive patients (61 male, median age 65
      years, range 51-82) were treated for CR. Seven patients were treated for
      bilateral CR, accounting for 86 reconstructions, 41 CEAs, and 45 CAS procedures.
      Fifty (58.1%) CRs were asymptomatic, and 36 (41.9%) CRs were symptomatic.
      Treatment for CR was recommended for any stenosis >70% based on duplex ultrasound
      imaging with a peak systolic flow of >200 cm/sec. RESULTS: There was no
      difference in age in the two groups. The incidence of atherosclerotic risk
      factors and comorbidity was similar in the two groups. All patients received
      aspirin as basic medical treatment, and 53 patients (61.6%) were on statin
      therapy. The time period from primary CEA to reoperation or CAS was significantly
      shorter in the CAS group than in the CEA group (54.1 vs. 85.34 months, p=0.003).
      Correspondingly, the proportion of early CR was significantly higher in the CAS
      group as well (20 vs. 5, p=0.001). There was no perioperative mortality (30 days)
      in the two groups. In the CEA group, four neurological complications were seen
      versus one in the CAS group (p=0.13). Wound site and cardiac complication rates
      were significantly higher in the CEA group (p=0.029) with a median follow-up of
      35 months (range 12-190). The overall actuarial survival after 60 months was 83%
      in the CEA group and 100% in the CAS group (p=0.87). Freedom from repeat
      intervention for re-recurrence was 89% in the CEA group and 95% in the CAS group
      (p=0.52). CONCLUSION: CAS is feasible and safe in treating CR. Furthermore,
      midterm overall survival and need for treatment of re-recurrence is equal to CEA.
      However, reoperation is an established option and remains the treatment of choice
      when contraindications for CAS are evident.

PMID- 19748765
TI  - Octogenarians are not at increased risk for periprocedural stroke following
      carotid artery stenting.
AB  - BACKGROUND: We analyzed the risk of adverse events following carotid angioplasty
      and stenting (CAS) in patients <80 years (group I) compared with those > or = 80
      years of age (group II). METHODS: Prospective data from 224 patients who
      underwent 235 consecutive CAS procedures at three participating institutions were
      reviewed retrospectively. All subjects were enrolled in Food and Drug
      Administration-approved clinical trials of CAS in high-risk patients or in
      institutional protocols. Procedural details and angiographic morphology were
      reviewed in all cases. All patients underwent independent neurological evaluation
      at 24hr and 30 days following CAS. RESULTS: Mean age was 69.9 years in the
      younger cohort and 83.5 years in the older group. Embolic protection devices were
      successfully deployed in 97.5% of cases in group I compared with 98.7% in group
      II (p=nonsignificant [NS]). Procedural success, defined as <30% residual stenosis
      after CAS, was achieved in all cases. Mean hospital stay was similar in the two
      groups. Transient ischemia attacks occurred in 1.9% in group I and 1.3% in group
      II (p=NS). Within 30 days of CAS, the risk of minor or major stroke (p=NS) as
      well as the composite risk of stroke (minor or major) and death was 2.5% in group
      I and 3.8% in group II (p=NS). Multivariate logistic regression analysis showed
      that absence of hypertension (odds ratioi [OR]=0.38, p=0.0352) and chronic renal
      insufficiency (OR=2.62, p=0.0238) were significant predictors of the composite
      end point of stroke and all-cause mortality. Kaplan-Meier analysis revealed that
      survival and freedom from the combined end point of stroke and all-cause
      mortality were similar for patients in groups I and II. CONCLUSION: Octogenarians
      are not at increased risk of periprocedural adverse events following CAS compared
      to younger patients. Exclusion of high-risk patients from CAS based on age alone
      is unjustified.

PMID- 19748766
TI  - Proxy reports of physical activity were valid in older people with and without
      cognitive impairment.
AB  - OBJECTIVE: To determine the validity of proxy reports of physical activity in
      people with symptoms of cognitive impairment. STUDY DESIGN AND SETTING: In the
      Canadian Study of Health and Aging, a multicenter prospective cohort study,
      someone close to the participant (proxy) reported exercise levels for people who
      screened positive for cognitive impairment or were institutionalized (n=2421),
      some of whom were subsequently diagnosed with cognitive impairment (n=1612) and
      some of whom were diagnosed as having no cognitive impairment (n=809). The
      reliability and validity of proxy reports of physical activity were examined by
      agreement with self-reports of physical activity (intraclass correlation
      coefficient) and by association with adverse health markers (Mantel-Haenzel
      chi(2)) and survival time (Cox proportional hazards). RESULTS: Proxy reports of
      physical activity had moderate interrater reliability (0.55, 95% confidence
      interval: 0.49-0.61, P<0.001). People in higher physical activity group had fewer
      adverse health outcomes than those in lower physical activity groups. Predictive
      validity was confirmed as people who had higher proxy-reported physical activity
      survived longer that those with lower physical activity. CONCLUSION: Proxy
      reported physical activity appears to be a valid estimate of physical activity in
      people with symptoms or a diagnosis of cognitive impairment.

PMID- 19748767
TI  - Susceptibility of Pseudomonas aeruginosa clinical isolates in Japan to doripenem
      and other antipseudomonal agents.
AB  - We investigated the susceptibility of 694 Pseudomonas aeruginosa clinical
      isolates to nine antipseudomonal agents including doripenem. Test strains were
      collected from 23 Japanese medical facilities from 1992 to 2004. Doripenem showed
      a minimum inhibitory concentration for 90% of the organisms (MIC(90)) of 8
      microg/mL, which was the lowest among the tested antipseudomonal agents. The
      MIC(90) of doripenem was 2-fold lower than that of meropenem, imipenem and
      amikacin and was > or =4-fold lower than that of piperacillin/tazobactam,
      ceftazidime, cefepime, ciprofloxacin and tobramycin. Amikacin showed the lowest
      rate of resistance against all clinical isolates (5.8%) followed by doripenem
      (7.1%). No remarkable changes were observed from 1992 to 2004 in the frequency of
      P. aeruginosa strains resistant to the tested agents, except for imipenem. Of 116
      ceftazidime-resistant strains, from 44.0% to 50.8% were susceptible to the three
      carbapenems, but only 2.6% to cefepime. Of 138 imipenem-resistant strains, from
      44.2% to 51.4% were susceptible to doripenem and both cephems, but 25.4% to
      meropenem. Doripenem was more active against imipenem- or ceftazidime-resistant
      strains than meropenem, although the activity of doripenem correlated well with
      that of meropenem. In conclusion, doripenem had the most potent in vitro activity
      against P. aeruginosa clinical isolates among the tested antibiotics. Considering
      the trend of antimicrobial resistance of the clinical isolates in well-focused
      surveillance, pseudomonal infections should be treated with appropriate
      chemotherapy using antimicrobial agents with potent antipseudomonal activity and
      low resistance rates, such as doripenem, in order to prevent the outbreak of
      resistant strains.

PMID- 19748768
TI  - Acute toxicities experienced during simultaneous integrated boost intensity
      modulated radiotherapy in head and neck cancers--experience from a north Indian
      regional cancer centre.
AB  - AIM: A prospective study was conducted to assess the feasibility of simultaneous
      integrated boost intensity-modulated radiotherapy (SIB IMRT) in our setting.
      Acute toxicities encountered during and immediately after treatment are reported.
      MATERIALS AND METHODS: Acute toxicity data prospectively collected during the
      treatment of the evaluable 28 patients with two SIB IMRT schedules were analysed.
      Toxicity was graded using the Common Terminology Criteria for Adverse Events
      version 3.0 system. Twenty-one patients were treated with the SIB72 schedule,
      delivering 72, 66 and 57 Gy in 33 fractions to the gross tumour volume, the high
      risk clinical target volume and the low-risk clinical target volume,
      respectively, whereas seven patients were treated with the SIB66 schedule,
      delivering 66, 60 and 54 Gy in 30 fractions to the above volumes. No chemotherapy
      was given during the course of treatment. Descriptive analysis of the incidence
      and actuarial analysis of the duration of toxicities are presented. RESULTS:
      Grade 3 or greater acute mucosal and actinic toxicity were seen 42.9 and 14.3% of
      the patients, respectively. Mucosal toxicity appeared by the second week in most
      patients. Atypical patterns of mucositis were encountered, including one patient
      with prolonged grade 4 mucosal ulceration in the SIB72 schedule. Grade 3 weight
      loss was seen in 10.57% of patients. Grade 3 pain was seen in 70% and grade 3
      dysphagia in 10% during treatment. CONCLUSION: SIB IMRT as used in this study was
      feasible, although associated with increased rates of mucosal and dermal
      toxicity.

PMID- 19748769
TI  - Human leukocyte antigen antibodies in chronic transplant vasculopathy-mechanisms
      and pathways.
AB  - Transplant recipients exhibiting posttransplant antibodies are at a higher risk
      for acute and chronic antibody mediated rejection (AMR). The primary alloantigens
      recognized by antibodies in recipients with AMR are the highly polymorphic HLA
      class I and class II molecules expressed on the surface of the endothelial cells
      (ECs) of the graft. Traditionally, anti-HLA antibodies were thought to mediate
      graft injury through complement-dependent mechanisms. However, recent studies
      indicate that antibodies can also contribute to alterations in EC function
      through complement-independent mechanisms by transducing intracellular signals.
      Anti-HLA antibodies transduce signals that are both pro-inflammatory and pro
      proliferative suggesting mechanistic roles in acute and chronic AMR.

PMID- 19748770
TI  - Lactose nano-probe optimized using response surface methodology.
AB  - A lactose nano-probe has been developed by immobilization of PsBGAL onto gold
      nanoparticles (AuNps). It is helpful for severe lactose intolerants for quality
      check of lactose hydrolyzed milk and estimation of hidden lactose present in
      variety of food products. Optimization of PsBGAL immobilization onto AuNps using
      spacer arm (cysteamine-glutaraldehyde) was carried out by response surface
      methodology (Box-Behnken design). The process has led to immobilization of enzyme
      onto AuNps with an efficiency of 140.81%. AuNp-PsBGAL was characterized using
      transmission electron microscopy, scanning electron microscopy and Fourier
      transform infrared spectroscopy. Immobilized enzyme showed broad temperature and
      pH optima and a significant enhancement in catalytic efficiency (V(max)/K(m))
      with respect to soluble PsBGAL. AuNp-PsBGAL was stable under dried conditions
      than wet conditions for 6 months with loss of 10.2% and 87.53%, respectively. It
      has reusability of over five batchwise uses, with almost no loss in activity.
      Hill's coefficient was found to be 1.71 corresponding to lactose concentration
      ranging from 0.1% to 2.0%.

PMID- 19748771
TI  - Investigation of the spatial distribution of glutathione redox-balance in live
      cells by using Fluorescence Ratio Imaging Microscopy.
AB  - The dynamics of redox elements in biologic systems is a major challenge for redox
      signaling and oxidative stress research. Oxidative stress or signaling events can
      affect sulfur switches differently, thus creating a variation in the spatial
      distribution of these redox states, which therefore act simultaneously as
      regulators and indicators of key cellular functions in both physiological and
      pathological settings. A gluthatione specific redox-sensitive protein (i.e. a
      mutant of the Yellow Fluorescent Protein (rxYFP)) has been found to equilibrate
      in vivo with the gluthatione/gluthatione disulfide (GSH:GSSG) redox couple.
      rxYFP, employed ratiometrically, allows to generate high resolution maps of the
      fraction of the reduced protein (R) inside a cell. Here we developed an
      analytical procedure able to investigate intracellular changes in the glutathione
      redox-balance, which can occur in live mammalian cells, based on the
      deconvolution of the histogram of redox maps of 293-TPhoenix human embryonic
      kidney cells. The intracellular spatial distributions of oxidized and reduced
      elements have been discriminated. Finally, by transfecting cells with human
      Glutaredoxin V (GRX-V), an enzyme deputed to maintain reduced the thiol groups of
      their partner proteins, we can disclose that the significant shift towards more
      reduced state, with respect to that recovered from non-transfected cells,
      consists, instead, in a shift towards reduced values of the high R region
      (reduced), while leaving unaltered the glutathione redox-balance of the
      intracellular side of the plasma membrane.

PMID- 19748772
TI  - Triple-helix DNA structural studies using a Love wave acoustic biosensor.
AB  - The development of sensors for detecting the conformation of surface-attached
      molecules is an emerging field with significance in the pharmaceutical industry
      and in drug design. In this work, triplex-forming oligos (TFOs), a separate class
      of non-natural DNA bending agents that can affect the mechanical properties of
      DNA through the formation of triple-helical structures of specific conformation
      and/or flexibility, are used as a model system in combination with an acoustic
      biosensor to determine molecular geometrical features. In practice, the degree of
      bending of a specific DNA target caused by a particular TFO was evaluated by
      measuring the ratio of acoustic energy change over phase change observed during
      the binding of pre-formed triplex DNA molecules to the device surface. The DNA
      bending angle derived via acoustic measurements is in excellent agreement with
      previously reported values using molecular biology techniques. The reported
      acoustic technique appears quite appealing for the biophysical study of DNA
      molecules providing rapid qualitative and quantitative information, at the same
      time holding promise to be developed as a high-throughput method for the
      evaluation of DNA conformational changes.

PMID- 19748773
TI  - Label-free photoelectrochemical immunoassay for alpha-fetoprotein detection based
      on TiO(2)/CdS hybrid.
AB  - A novel photoelectrochemical immunosensor based on TiO(2)/CdS hybrid modified
      electrode was developed. The TiO(2)/CdS hybrid modified electrode was obtained by
      alternately dipping the TiO(2) modified indium-tin oxide (ITO) electrode into the
      [Cd(NH(3))(4)](2+) and S(2-) solution repeatedly. Compared with the routine
      method using Cd(2+) solution for CdS deposition, the as obtained TiO(2)/CdS
      electrode showed enhanced photocurrent intensity with fewer coating times. After
      the ITO/TiO(2)/CdS electrode was coated with chitosan (CS), alpha-fetoprotein
      (AFP) antibodies were covalently conjugated on the surface of the electrode.
      Thus, a label-free photoelectrochemical immunosensor for the detection of AFP was
      developed by monitoring the changes in the photocurrent signals of the electrode
      resulting from the immunoreaction. The immunosensor displayed a linear response
      to AFP in the ranges from 50pg/mL to 50ng/mL with a relatively low detection
      limit of 40pg/ml. The photoelectrochemical results for the detection of AFP in
      five human sera showed acceptable accuracy. The method is simple, sensitive and
      specific. Moreover, the studied immunosensor possessed acceptable reproducibility
      and storage stability. The proposed methodology was potentially attractive for
      clinical immunoassay.

PMID- 19748774
TI  - Microbial enzymatic activities in a pilot-scale MBR experimental plant under
      different working conditions.
AB  - Phosphatases, glucosidase, protease, esterase and dehydrogenase activities in a
      MBR (membrane bioreactor) system equipped with ultrafiltration membranes for the
      treatment of real urban wastewater were measured at different volatile suspended
      solid (VSS) concentrations, total suspended solid (TSS) concentrations, hydraulic
      retention times (HRT), temperatures and inflow rates. The results showed the
      capacity of the MBR system to remove COD and BOD(5) at TSS between 7200 and
      13,300 mg/L; HRT values of 8.05 and 15.27 h; inflow rates of 14.67 and 27.81 L/h;
      and temperatures between 4 and 27 degrees C. The enzymatic activities are
      influenced by increases in VSS and TSS concentrations. These results suggest that
      the ability to get adapted to environmental changes of the bacterial populations
      and their microbial enzymatic activities is essential to understand the
      biological processes that occur in MBR systems and crucial for proper urban
      wastewater treatment when using MBR technologies.

PMID- 19748775
TI  - Characterization of the curing process from high-solids anaerobic digestion.
AB  - A laboratory-scale study was completed to simulate aerobic curing of solid-phase
      residue (digestate) from an anaerobic reactor fed a mixture of food and landscape
      wastes. The degree of organic stabilization was determined through routine
      analysis of oxygen uptake rates, percent O(2), temperature, volatile solids, and
      Solvita Maturity Index; measurements of ammonia and volatile fatty acid (VFA)
      concentrations served as indicators of phytotoxicity. Results suggest that
      stabilization of organics and elimination of phytotoxic compounds from anaerobic
      digestate preceded significant reduction of each volatile sulfur compound (VSC)
      detected (hydrogen sulfide, methanethiol, and dimethyl sulfide). Within 10-15
      days of curing, stabilization of organics was achieved and phytotoxic compounds
      were eliminated, whereas reduction of VSCs to low levels required 15-20 days of
      curing. Based on these results, incomplete curing and anaerobic microenvironments
      within a curing facility may increase odor potential via formation of VSCs,
      whereas sufficiently cured digestate will resist VSC formation, despite the onset
      of anaerobic conditions.

PMID- 19748776
TI  - Bioenergy production for CO2-mitigation and rural development via valorisation of
      low value crop residues and their upgrade into energy carriers: a challenge for
      sunflower and soya residues.
AB  - The present study concerns the energetic valorization of sunflower and soya
      residues by air fixed-bed gasification. The main process parameters that have
      been investigated were the temperature and air equivalence ratio. Experimental
      results indicated that the high temperature and air had a positive effect in gas
      yield for both residues by ensuring mild oxidative conditions. Gasification gas
      composition showed different trends of H(2)/CO ratio for the two residues at low
      equivalence ratios. The LHV of the produced gas from both residues varied from
      6.84 to 12 MJ/Nm(3). The energy recovery achieved via gasification could reach
      0.07 and 0.02 per acre of cultivated area for the sunflower and soya residues,
      respectively, in terms of tons of oil equivalent. Sunflower shown higher oil
      production and energy recovery than soya did. The results of the present study
      indicate the viability of alternative energy production from agricultural biomass
      by gasification. Such residues could comprise an attractive renewable source of
      energy for covering additional energy demands in agricultural regions through
      exploitation in small gasification systems.

PMID- 19748777
TI  - Aquatic worms grown on biosolids: biomass composition and potential applications.
AB  - The increasing production of biological waste sludge from wastewater treatment
      plants is a problem, because stricter legislation inhibits the use of traditional
      disposal methods. The use of the aquatic worm Lumbriculus variegatus can minimise
      sludge production. Because the worms can feed and grow on this waste sludge,
      valuable compounds that are present in the sludge can be recovered by the worms.
      This paper describes a systematic approach for finding possible applications of
      the produced biomass. The worm biomass mainly consists of protein and smaller
      fractions of fat, sugar and ash. It also contains low concentrations of heavy
      metals. The potential produced amount is relatively small, compared to other
      waste streams, and is produced decentrally. Therefore, the most promising
      applications are specific components of the biomass, for example specific amino
      acids or fatty acids. However, until the process is optimized and there is a
      stable supply of worms, the focus should be on simple applications, later on
      followed by specific applications, depending on the market demand. Worm biomass
      grown on clean sludges has a broader application potential, for example as
      consumption fish feed.

PMID- 19748778
TI  - Pyrazole NNRTIs 4: selection of UK-453,061 (lersivirine) as a development
      candidate.
AB  - We prepared three discreet cohorts of potent non-nucleoside HIV reverse
      transcriptase inhibitors (NNRTIs) based on the recently reported 3
      cyanophenoxypyrazole lead 3. Several of these compounds displayed very promising
      anti-HIV activity in vitro, safety, pharmacokinetic and pharmaceutical profiles.
      We describe our analysis and conclusions leading to the selection of alcohol 5
      (UK-453,061, lersivirine) for clinical development.

PMID- 19748779
TI  - Small kinase assay panels can provide a measure of selectivity.
AB  - In this Letter, a novel strategy for assessment of ligand promiscuity is
      described. By using a carefully selected small set of kinases together with
      multivariate statistical methods, a measure of selectivity can be estimated. This
      will facilitate an appropriate selection of compounds for further development in
      lead generation and optimization.

PMID- 19748780
TI  - Discovery of disubstituted phenanthrene imidazoles as potent, selective and
      orally active mPGES-1 inhibitors.
AB  - Phenanthrene imidazoles 26 and 44 have been identified as novel potent, selective
      and orally active mPGES-1 inhibitors. These inhibitors are significantly more
      potent than the previously reported chlorophenanthrene imidazole 1 (MF63) with a
      human whole blood IC50 of 0.20 and 0.14 microM, respectively. It exhibited a
      significant analgesic effect in a guinea pig hyperalgesia model at oral doses as
      low as 14 mg/kg. Both active and selective mPGES-1 inhibitors (26 and 44) have a
      relatively distinct pharmacokinetic profile and are suitable for clinical
      development.

PMID- 19748781
TI  - Synthesis and biological evaluation of new heterocyclic quinolinones as anti
      parasite and anti-HIV drug candidates.
AB  - We have synthesized quinolinones with potential antiparasitic and anti-HIV
      activities by an original two-step method involving microwave irradiation and
      have evaluated their activities against Plasmodium falciparum, Leishmania
      donovani, Trichomonas vaginalis, and HIV. None of the tested compounds had been
      previously described using this method of synthesis. One of the compounds had
      interesting antiparasitic and anti-HIV activity, which could be improved by
      substitution with different radicals.

PMID- 19748782
TI  - Discovery of highly potent novel antifungal azoles by structure-based rational
      design.
AB  - On the basis of the active site of lanosterol 14alpha-demethylase from Candida
      albicans (CACYP51), a series of new azoles were designed and synthesized. All the
      new azoles show excellent in vitro activity against most of the tested pathogenic
      fungi, which represent a class of promising leads for the development of novel
      antifungal agents. The MIC(80) value of compounds 8c, 8i and 8n against C.
      albicans is 0.001 microg/mL, indicating that these compounds are more potent than
      fluconazole, itraconazole and voriconazole. Flexible molecular docking was used
      to analyze the structure-activity relationships (SARs) of the compounds. The
      designed compounds interact with CACYP51 through hydrophobic, van der Waals and
      hydrogen-bonding interactions.

PMID- 19748783
TI  - Thienopyrimidine-based P2Y12 platelet aggregation inhibitors.
AB  - Herein we describe the design and synthesis of a novel series of potent
      thienopyrimidine P2Y12 inhibitors and the negative impact protein binding has on
      the inhibition of platelet aggregation.

PMID- 19748784
TI  - ABC transporters: a riddle wrapped in a mystery inside an enigma.
AB  - ATP-binding cassette (ABC) transporters form one of the largest and most ancient
      of protein families. ABC transporters couple hydrolysis of ATP to vectorial
      translocation of diverse substrates across cellular membranes. Many human ABC
      transporters are medically important in causing, for example, multidrug
      resistance to cytotoxic drugs. Seven complete prokaryotic structures and one
      eukaryotic structure have been solved for transporters from 2002 to date, and a
      wealth of research is being conducted on and around these structures to resolve
      the mechanistic conundrum of how these transporters couple ATP hydrolysis in
      cytosolic domains to substrate translocation through the transmembrane pore. Many
      questions remained unanswered about this mechanism, despite a plethora of data
      and a number of interesting and controversial models.

PMID- 19748785
TI  - Design, synthesis, and X-ray crystal structures of 2,4-diaminofuro[2,3
      d]pyrimidines as multireceptor tyrosine kinase and dihydrofolate reductase
      inhibitors.
AB  - To optimize dual receptor tyrosine kinase (RTK) and dihydrofolate reductase
      (DHFR) inhibition, the E- and Z-isomers of 5-[2-(2-methoxyphenyl)prop-1-en-1
      yl]furo[2,3-d]pyrimidine-2,4-diamines (1a and 1b) were separated by HPLC and the
      X-ray crystal structures (2.0 and 1.4A, respectively) with mouse DHFR and NADPH
      as well as 1b with human DHFR (1.5A) were determined. The E- and Z-isomers adopt
      different binding modes when bound to mouse DHFR. A series of 2,4-diaminofuro[2,3
      d]pyrimidines 2-13 were designed and synthesized using the X-ray crystal
      structures of 1a and 1b with DHFR to increase their DHFR inhibitory activity.
      Wittig reactions of appropriate 2-methoxyphenyl ketones with 2,4-diamino-6
      chloromethyl furo[2,3-d]pyrimidine afforded the C8-C9 unsaturated compounds 2-7
      and catalytic reduction gave the saturated 8-13. Homologation of the C9-methyl
      analog maintains DHFR inhibitory activity. In addition, inhibition of EGFR and
      PDGFR-beta were discovered for saturated C9-homologated analogs 9 and 10 that
      were absent in the saturated C9-methyl analogs.

PMID- 19748786
TI  - Synthesis and pharmacological exploitation of clioquinol-derived copper-binding
      apoptosis inducers triggering reactive oxygen species generation and MAPK pathway
      activation.
AB  - In the present study, we carried out Mannich-type reaction to synthesize
      clioquinol-derived 7-methyl-arylsulfonylpiperazine analogs with improved growth
      inhibitory effects. 11 bearing 5-nitro group on the quinoline ring exhibited 26
      fold more potent than that of clioquinol against HeLa cells with a GI(50) value
      of 0.71 microM. In addition, 11 revealed synergistic effects on the growth
      inhibition of HeLa cells with GI(50) values of 0.65, 0.25, and 0.06 microM in the
      presence of 1, 10, and 50 microM copper, respectively. Consistent to the
      clioquinol-mediated apoptosis, mechanistic study indicates that 9- and 11-induced
      growth inhibition is attributed to caspase-dependent pathway. Detection of
      reactive oxygen species in response to clioquinol, 9 and 11 confirmed that ROS
      was dramatically stimulated in the presence of copper and partially abolished
      upon treatment of 1mM tempol. Further study indicated that 9- and 11-mediated
      induction of oxidative stress by ROS generation resulted in the activation MAPK
      pathway.

PMID- 19748787
TI  - Effect of wedge filter and field size on photoneutron dose equivalent for an 18MV
      photon beam of a medical linear accelerator.
AB  - Photoneutrons produced during radiation therapy with high energy photons is the
      main source of unwanted out-of-field received doses of patients. To analyze the
      neutron dose equivalent (NDE) for wedged beams and its variation with field size,
      Monte Carlo (MC) modeling of an 18MV photon beam was performed using MCNPX MC
      code. The results revealed that the NDE is on average 6.5 times higher for wedged
      beams. For open beams, the NDE decreased with increasing field size especially
      for field sizes >20x20cm(2). While, for wedged beams, the NDE increased with
      field size. It was suggested that the increase of NDE for wedged beams should be
      taken into account in radiation-induced secondary cancer risk estimations and
      radiation protection calculations.

PMID- 19748788
TI  - Head and neck lesions of Kimura's disease: exclusion of human herpesvirus-8 and
      Epstein-Barr virus by in situ hybridisation and polymerase chain reaction. An
      immunohistochemical study.
AB  - INTRODUCTION: Kimura's disease (KD) is a chronic inflammatory disorder,
      characterised by tumour-like lesions in the head and neck region, producing
      salivary gland nodules and lymph node enlargement. Many authors suggest that KD
      is a reactive immunological disorder; however, its aetiology remains unknown.
      AIMS: To study immunohistochemical characteristics of head and neck lesions of KD
      (H&N-KD) and to investigate the possible role of human herpesvirus-8 (HHV-8) and
      Epstein-Barr virus (EBV) in the development of H&N-KD. PATIENTS AND METHODS: This
      study enrolled five H&N-KD specimens from three patients treated between 1995 and
      2005 at Pitie-Salpetriere University Hospital, Paris, France. Immunohistochemical
      studies were performed on formalin-fixed, paraffin-embedded tissue. HHV-8 DNA was
      determined by polymerase chain reaction (PCR) analysis, whilst EBV sequences were
      identified by PCR and in situ hybridisation. RESULTS: The immunohistochemical
      studies revealed CD20+ germinal centres with prominent staining of CD23+
      dendritic reticular cells, surrounded by numerous interfollicular CD3+, and CD4+
      or CD8+ T-cells. Factor VIII-related antigen, CD31 and CD34 occurred in the thin
      walled blood vessels. The reactivity of CD1a, HHV-8 and EBV-associated latent
      membrane protein 1-EBV (LMP1-EBV) were negative, and in situ hybridisation
      confirmed the lack of EBV DNA. No patient recalled an external insult or chronic
      irritation. CONCLUSIONS: The results of this study indicate the reactive nature
      of H&N-KD (or a subset of H&N-KD), and it is unlikely that HHV-8 and EBV play a
      role in the pathogenesis of the lesion. However, the patients in this series did
      not have previous history of trauma or chronic irritation; thus, a neoplastic
      origin could not be excluded. Further multicentre studies based on more specimens
      are warranted.

PMID- 19748791
TI  - Factors influencing survival and postoperative quality of life after mitral valve
      reconstruction.
AB  - OBJECTIVE: Mitral valve reconstruction (MVR) is the preferred treatment for
      regurgitant lesions. Clinical benefit is well documented, but comparative data
      scrutinising factors influencing survival and postoperative quality of life (QOL)
      in different subsets of patients are missing. We hypothesised that mitral valve
      reconstruction for mitral regurgitation benefits the patients, regardless of the
      valve pathology. METHODS: In this study, 663 consecutive patients undergoing
      mitral valve reconstruction using Carpentier techniques were assigned to four
      different groups. Aetiology of mitral regurgitation was degenerative (DEG) in 372
      (56.1%) patients and ischaemic (ISC) in 157 (23.6%). Cardiomyopathy (CMP) was
      present in 23 (3.4%) cases and combined degenerative regurgitation plus coronary
      artery disease (DEG+CAD) in 111 (16.7%) patients. Survival was evaluated using a
      Cox proportional hazards model. Postoperative QOL was assessed using the short
      form (SF)-36 questionnaire in a multivariate analysis of covariance. RESULTS: The
      overall 30-day mortality was 1.1% (0.3%, 1.9%, 0% and 2.7% for groups DEG, ISC,
      CMP and DEG+CAD, respectively). The median preoperative NYHA class and grade MI
      was 3 and evenly distributed between groups. After a mean follow-up of 4.1+/-3.4
      years, MVR proved to be effective in all groups with 90.3% of patients in the
      NYHA classes I and II (p<0.001). At 5 years, unadjusted survival was 90.3%,
      69.7%, 50.5% and 86.2%. However, after correcting for age, ejection fraction,
      chronic obstructive pulmonary disorder (COPD), renal insufficiency and the
      preoperative NYHA class, survival in groups ISC and DEG+CAD was comparable. Group
      allocation was not a predictor for late death. Postoperative QOL was inferior in
      female patients in all SF-36 scales (p<0.01) and was impaired by co-morbidities.
      QOL scores were best for patients in group DEG and worst in group CMP. In a
      multivariate model correcting for gender, age and co-morbidities (COPD, treated
      diabetes, renal insufficiency, subjective heart rhythm, preoperative NYHA class
      and previous myocardial infarction), postoperative QOL was comparable between
      groups. For the majority of patients with degenerative MR, postoperative life
      expectancy as well as QOL is similar to a normal population. CONCLUSIONS: MVR was
      safely and effectively accomplished in all groups. Survival and postoperative QOL
      was determined by left ventricular function and co-morbidities rather than MR
      aetiology.

PMID- 19748792
TI  - Pneumomediastinum: is this really a benign entity? When it can be considered as
      spontaneous? Our experience in 47 adult patients.
AB  - OBJECTIVE: Spontaneous pneumomediastinum is uncommon and is traditionally
      considered a benign, self-limited disorder that usually occurs in young adults
      without any apparent precipitating factor or disease. The purpose of this study
      is to present 47 new cases because of their different clinical behaviours.
      METHODS: A descriptive, retrospective case series was conducted to identify adult
      patients with spontaneous pneumomediastinum who were diagnosed and treated in a
      single institution between 2000 and 2008. RESULTS: Forty-seven patients were
      identified, including 33 men and 14 women with a mean age of 27.3 years (range,
      16-42 years). Acute-onset chest pain was the predominant symptom at presentation
      (59.5%); subcutaneous emphysema was the most common sign (42.9%). The most common
      predisposing factor was consumption of illegal drug (cocaine): it was not a
      regular and long-term abuse but an occasional trend, coinciding few hours before
      presenting symptoms (55%). Notably, in one case, a bad outcome with mediastinal
      shift and important tracheal compression necessitated a right thoracotomy to open
      the mediastinal pleura. CONCLUSIONS: (1) It is known that occasional consumption
      of cocaine causes diffuse alveolar damage, haemorrhage, etc. The cause-effect
      relationship consumption-appearance in a few hours of spontaneous
      pneumomediastinum leads us to appreciate this form of consumption as a causal
      factor rather than a predisposing/precipitating factor as it appears in the
      literature on the topic. (2) Spontaneous pneumomediastinum is considered a benign
      disorder but, as shown by our series, a bad outcome may represent an immediate
      life-threatening condition, forcing an invasive manoeuvre. We always recommend
      performing a chest CT scan on admission to predict the evolution.

PMID- 19748793
TI  - Comorbidity, disability and geriatric syndromes in elderly breast cancer
      survivors. Results of a single-center experience.
AB  - Advancing age is a major risk factor for breast cancer. Long-term follow-up is
      recommended after diagnosis and treatment of early breast cancer. With older age,
      the risk of comorbid conditions and functional impairment increases. A useful
      tool in the management and follow-up of these elderly patients could be a
      comprehensive geriatric assessment (CGA). PURPOSE: A descriptive, transversal
      study was carried out of the prevalence of other comorbidities and of the
      functional impairment in elderly patients on follow-up after curative treatment
      of early breast cancer. PATIENTS: Women aged> or =70 at diagnosis; early breast
      cancer treated surgically. No disease recurrence allowed. METHODS: CGA was
      conducted in an oncology unit using screening instruments (activities of daily
      living [ADL]; instrumental activities of daily living [IADL]; body mass index
      [BMI]; geriatric depression scale [GDS]). Cognitive status was reported by the
      patient. Comorbidity was classified using the Charlson score. RESULTS: From
      January 2005 to June 2006 91 patients were seen. Mean age at surgery: 76 (70-92).
      Mean age at CGA: 80 (71-95). Aged population (almost 25% were more than 84 at the
      time of CGA). Median follow-up: 5 years (range 1-12). Good performance status
      (PS) in most (only 9% PS 2). Eighty-three percent were fully independent for ADL
      and 71% for IADL. IADL most affected was the ability to drive/use public
      transport. Twenty-eight percent had geriatric syndromes and 23% were classified
      as "frail". Increased age was associated with worsening PS (p=0.0001) and
      worsening function (ADL p<0.0001 and IADL p<0.0001). The study is remarkable for
      the high comorbidity index found in the elderly survivors. Median Charlson score
      was 2 (1-6). More than 75% of the series had a score >/=4. Cardiovascular disease
      (hypertension) was the most prevalent comorbid condition. As an effect of this,
      the majority of patients were polymedicated (75% took more than six drugs).
      Comorbidity was independent of functionality and age. CONCLUSIONS: Older patients
      with early breast cancer on follow-up have a high prevalence of comorbidity. In
      our series, function and independence were maintained. A selection bias cannot be
      excluded, as the fitter patients are those who usually continue with the follow
      up, while those frail patients who do not continue because of their functional
      impairment are usually lost.

PMID- 19748794
TI  - Beta-cell deterioration during diabetes: what's in the gun?
AB  - Clinical management of patients with type 2 diabetes (T2D) successfully prevents
      extreme hyperglycemia but does not precisely control glucose levels throughout
      the day. The pathogenesis of T2D is akin to a double-barrel shotgun. The first
      trigger causes an explosion that sets genetic expression of the disease in
      motion; the second trigger discharges a host of environmental factors that worsen
      its clinical course. Candidate shells include glucolipotoxicity, cytokines,
      oxidative and endoplasmic reticulum stress and insulin resistance. This review
      considers how each candidate adversely impacts beta-cell function to create the
      downward spiral of glycemic control. Their roles in pathogenesis raise
      possibilities for new drug therapies designed to protect against adverse effects
      of residual hyperglycemia in patients treated with conventional drugs.

PMID- 19748795
TI  - Angiotensin II type-1 receptor antagonist attenuates LPS-induced acute lung
      injury.
AB  - Angiotensin II is able to trigger inflammatory responses through an angiotensin
      II type 1 (AT1) receptor. The role of AT1 receptor in acute lung injury (ALI) is
      poorly understood. Mice were randomly divided into three groups (n=40 each
      groups): NS group; LPS group (2mg/kg LPS intratracheally); and LPS+ZD 7155 group,
      10mg/kg ZD 7155 (an AT1 receptor antagonist) intraperitoneally 30 min prior to
      LPS exposure. Samples from the lung were isolated and assayed for histopathology
      analyses or proinflammatory gene expressions, angiotensin II receptors
      expressions and nuclear factors activities. LPS exposure resulted in severe ALI,
      elevated levels of TNF-alpha and IL-1 beta mRNA expressions, and increased
      activities of NF-kappaB and activated protein (AP)-1. Upregulation of AT1
      receptor and down-regulation of AT2 receptor were also observed after LPS
      challenge. Pretreatment with ZD 7155 significantly inhibited the increase of AT1
      receptor expression and upregulated AT2 receptor expression. ZD 7155 also reduced
      the mRNA expression of TNF-alpha and IL-1 beta, inhibited the activation of NF
      kappaB and AP-1, and improved lung histopathology. These findings suggest that
      antagonism of AT1 receptor inhibits the activation of NF-kappaB and AP-1 in the
      lung, which may mediate the release of TNF-alpha and IL-1 beta and contribute to
      LPS-induced ALI.

PMID- 19748796
TI  - Hepatic monocyte chemoattractant protein-1 is upregulated by dietary cholesterol
      and contributes to liver steatosis.
AB  - To assess the role of monocyte chemoattractant protein-1 (MCP-1/CCL2) in the
      development of fatty liver, we have used LDLr(-/-) mice as an animal model of
      high-fat, high-cholesterol diet-induced liver steatosis. The rapid dietary
      induction of hepatic mRNA MCP-1 expression was paralleled by a concomitant
      increase in plasma MCP-1 that was strongly associated with the degree of liver
      steatosis. Hepatocytes showed an intense immunoreactivity for MCP-1 that was
      mainly located surrounding the hepatic lipid droplets. The intake of cholesterol
      also increased the concentration of MCP-1 in liver homogenates. This was
      accompanied by a differential expression of members of the PPAR family.
      Additionally, complete MCP-1 deficiency prevents the development of liver
      steatosis in LDLr(-/-) mice and partial deficiency is accompanied by a certain
      protective effect. Our data also suggest that MCP-1 may be important in the
      regulation of hepatic insulin resistance and may represent a link between
      inflammation and metabolic diseases. We conclude that dietary cholesterol
      upregulation of hepatic MCP-1 may help to understand the role of circulating MCP
      1 in conditions where liver derangements are clinically important and in the
      association of liver steatosis with the metabolic syndrome.

PMID- 19748797
TI  - Re: Uterine artery embolization fatality.

PMID- 19748798
TI  - Effect of over-the-counter fish-oil administration on plasma Lp(a) levels in an
      end-stage renal disease population.
AB  - OBJECTIVE: This study sought to examine the effect of n-3 supplementation on
      lipoprotein(a) (Lp(a)) levels in end-stage renal disease (ESRD) patients
      undergoing chronic hemodialysis. DESIGN: The present study was conducted using a
      double-blind, permuted-randomized, controlled experimental protocol. SETTING:
      This study took place at the Central Texas Nephrology Associates Dialysis Clinic
      (Waco, TX). PATIENTS: Patients with ESRD and associated with the Central Texas
      Nephrology Associates who were undergoing chronic hemodialysis participated in
      this study. INTERVENTION: Patients with ESRD were followed prospectively while
      receiving supplements of fish oil (treatment, eicosapentaenoic acid, 0.96g/day,
      and docosahexaenoic acid, 0.6g/day) or corn oil (control subjects) for 6 months.
      After a 12-hour fast, participants donated 12mL of blood for analysis of Lp(a) at
      baseline and at 6 months. MAIN OUTCOME MEASURE: The comparison of Lp(a)
      concentration by group at 6 months was the primary outcome measure of the study.
      RESULTS: Our study suggests that fish-oil supplementation did not decrease levels
      of Lp(a) (P=.66), compared with control subjects. CONCLUSION: We failed to show a
      significant effect of 6 months of over-the-counter fish-oil supplementation on
      Lp(a) status in an ESRD population, although results from this study support
      findings from other studies suggesting that African Americans have higher Lp(a)
      concentrations than persons of Caucasian decent.

PMID- 19748799
TI  - Dietary intakes of fiber and magnesium and incidence of metabolic syndrome in
      first year after renal transplantation.
AB  - OBJECTIVE: Considering the high prevalence of metabolic syndrome (MetS) and the
      associated cardiovascular disease mortality after renal transplant, and
      considering that the lack of prospective studies regarding the role of fiber and
      magnesium in MetS prevention after transplant precludes definitive
      recommendations, we prospectively evaluated the potential role of fiber and
      magnesium intake in the incidence of MetS at 1 year after renal transplantation.
      DESIGN: This was a prospective cohort study. SETTING, PARTICIPANTS, AND
      MEASUREMENTS: We included 160 recipients of kidney transplant (100 men and 60
      women) aged over 18 years who were free of MetS or diabetes at time of
      transplant, and followed these patients for 1 year. METHODS: The usual dietary
      intakes were assessed with a Willett-format 168-item food-frequency
      questionnaire. We defined MetS according to modified Adult Treatment Panel III
      guidelines. We categorized participants by tertiles of dietary fiber and
      magnesium. To determine associations of fiber and magnesium intake with MetS
      incidence 1 year posttransplant, we used multivariable logistic regression.
      RESULTS: After controlling for potential confounders, including baseline body
      mass index and energy intake, subjects within the highest tertile of fiber intake
      had a lower odds ratio for incident MetS (odds ratio, 0.41; 95% confidence
      interval, 0.08 to 0.99; P < .05 for trend) than those in the lowest tertile.
      There was no significant overall association between magnesium intake and MetS.
      CONCLUSIONS: These findings support current dietary recommendations to increase
      intakes of fiber-rich foods as a primary preventive approach against MetS and
      cardiovascular disease, which are very prevalent after renal transplant.

PMID- 19748800
TI  - Alternative humeral tubercle fixation in shoulder hemiarthroplasty for fractures
      of the proximal humerus.
AB  - HYPOTHESIS: We hypothesize that the sling technique provides better long term
      tuberosity fixation in hemiarthroplasty for severe fractures of the proximal
      humerus. BACKGROUND: After hemiarthroplasty for proximal humeral fractures,
      problems exist with deterioration of shoulder function by secondary displacement
      of the initially fixated humeral tuberosities. This study evaluated a new
      technique for fixation of the greater and lesser tuberosities in uncemented
      hemiarthroplasties in severely displaced 3- or 4-part proximal humeral fractures.
      MATERIALS AND METHODS: A consecutive series of 31 uncemented hemiarthroplasties
      using the new sling technique to repair the tuberosities was evaluated clinically
      and radiographically with special emphasis on the head-to-tuberosity distance
      (HTD). A historical cohort of 10 similar uncemented hemiarthroplasties was the
      control group in which the drill-hole technique was used for fixation of the
      humeral tuberosities. RESULTS: The sling technique had an overall better
      tuberosity positioning in terms of HTD compared with the drill-hole technique (8
      vs 1 mm; P = .025, U test). There were significantly more normal HTD values in
      the sling-technique group (81% vs 44%; P = .032, chi(2) test). In the anatomic
      HTD group, the Constant score (70 vs 52; P = .009), patient satisfaction (7.1 vs
      5.7; P = .038), and visual analog scale score (3.2 vs 5.2; P = .025) were
      statistically significantly superior compared with the nonanatomic HTD group.
      CONCLUSION AND DISCUSSION: The sling technique for tuberosity fixation seems to
      provide solid fixation. In this study, anatomic HTD fixation was associated with
      significantly better functional outcome, patient satisfaction, and pain scores.

PMID- 19748801
TI  - The origin of the long head of the triceps: a cadaveric study.
AB  - HYPOTHESIS: There is a paucity of literature examining the origin, size, and
      capsular contribution of the long head of the triceps brachii muscle. We
      hypothesize that there is a more extensive origin and capsular contribution than
      previously described. MATERIALS AND METHODS: Twenty fresh, frozen cadaveric
      specimens were dissected from a posterior and anterior approach exposing the long
      head of the triceps and the inferior capsule. The origin and size of the long
      head of the triceps and contribution to the capsule was documented. RESULTS: The
      average age of the specimens was 65.8. At the scapula, the tendon width averaged
      2.69cm at the insertion and the thickness averaged 0.47cm laterally and 0.29cm
      medially. The bony origin extended on the lateral border dorsal surface of the
      scapula in addition to the infraglenoid tubercle. The long head of the triceps
      gave a capsular contribution in each specimen. This contribution measured 1.43cm
      from superior to inferior and 1.01cm from anterior to posterior after dissecting
      the capsule off the glenoid. DISCUSSION: We found the origin of the long head of
      the triceps had a more extensive bony attachment on the scapula then previously
      described. In addition, the long head of the triceps has a consistent
      contribution to the inferior shoulder capsule. CONCLUSION: The anatomic origin of
      the long head of the triceps gives a capsular contribution to the inferior
      glenohumeral capsule. The triceps may be affected by open and arthroscopic
      procedures that release or shift the posterior inferior glenohumeral capsule.
      LEVEL OF EVIDENCE: Cadaveric study.

PMID- 19748802
TI  - Treatment of proximal humerus fractures with locking plates: a systematic review.
AB  - HYPOTHESIS: Locking plates with special configuration for the anatomic region of
      the proximal humerus have been introduced recently to address the difficulties of
      stabilizing proximal humeral fractures. The purpose of this study was to carry
      out a systematic review of the literature on the efficacy and early to medium
      term functional results of locking plates for stabilization of proximal humeral
      fractures. METHODS: Using the PubMed database, a systematic review of the English
      and German literature was carried out in order to assess the efficacy and
      complications related to the use of these plates and the patients' functional
      outcome, using the key words "locking plates proximal humeral fractures,"
      "angular stability plates proximal humeral fractures," "PHILOS plate," and "LPHP
      plate." Our criteria for eligibility were clinical studies with more than ten
      cases followed-up, adult patients, and adequate data provided at least in terms
      of implant related complications. Articles written in English and German language
      were included. Exclusion criteria were: studies dealing exclusively with 2-part
      fractures (since this category has a more favorable outcome); experimental
      studies; case reports; and, literature other than English or German. Each one of
      the articles was evaluated for quality of the study using the Structured
      Effectiveness Quality Evaluation Scale (SEQES). RESULTS: Twelve studies including
      791 patients met the inclusion criteria. Patients in these studies continued to
      improve up to one year, achieving a mean Constant score of 74.3. The incidence of
      the reported complications was: avascular necrosis 7.9%, screw cut-out 11.6% and
      re-operation rate 13.7%. DISCUSSION: The high incidence of cut-out may be
      secondary to the rigidity of the implant in combination with medial inadequate
      support, in cases compromised by severe underlying osteoporotic bone. Definition
      of indications for the use of locking plates and attention on technical aspects
      of applying them would help optimization of the results. LEVEL OF EVIDENCE:
      Systematic Review.

PMID- 19748803
TI  - Heat, humidity and horse welfare in the Olympic Games: learning from history.

PMID- 19748804
TI  - Stay afloat in the tsunami: a focus on clinical relevance when partitioning
      reference intervals.

PMID- 19748805
TI  - Magnetic resonance imaging of cerebral involutional changes in dogs as markers of
      aging: an innovative tool adapted from a human visual rating scale.
AB  - The dog is increasingly considered as a natural animal model for the study of
      normal and pathological human brain aging, because it exhibits anatomical,
      biochemical and cognitive changes that parallel those seen in humans. This study
      presents a novel visual semi-quantitative rating scale of canine cerebral
      magnetic resonance imaging (MRI). Ninety-eight dogs of both sexes from 27 pure
      breeds, aged 2-15 years, were used. The results suggest that (like in humans)
      both hippocampal and progressive global atrophy are characteristic features that
      correlate with aging. When classified according to head shape, cerebral atrophy
      was highest in mesaticephalic and brachycephalic dogs. This is the first MRI
      study to characterise a simple, rapid tool for studying age-related canine brain
      changes that can even be applied by non-experienced observers. The results
      confirm the possibility of transferring innovative tools developed for human
      diagnosis to the veterinary field.

PMID- 19748806
TI  - Invasion of endothelial cells by systemic and nasal strains of Haemophilus
      parasuis.
AB  - Haemophilus parasuis is a respiratory commensal in healthy piglets, but can also
      produce invasive disease and meningitis, which requires the ability to cross the
      blood-brain barrier. This study determined the capacity of well-characterised
      virulent and non-virulent strains of H. parasuis, as well as other field strains,
      to adhere to and invade PBMEC/C1-2 endothelial cells. Virulent strains were
      derived from systemic lesions, conformed to the systemic clade on multilocus
      sequence typing (MLST) and were phagocytosis- and serum-resistant. Non-virulent
      strains were derived from the nostrils of healthy piglets, belonged to the nasal
      clade on MLST and were phagocytosis- and serum-sensitive. Virulent strains mostly
      were more invasive than non-virulent strains, although one virulent strain was
      unable to invade. Invasion of endothelial cells is a virulence mechanism of H.
      parasuis that may be related to the ability of some strains to cause meningitis.

PMID- 19748807
TI  - Effect of ketamine on the limb withdrawal reflex evoked by transcutaneous
      electrical stimulation in ponies anaesthetised with isoflurane.
AB  - The purpose of this study was to evaluate the anti-nociceptive activity of
      ketamine and isoflurane in horses using a limb withdrawal reflex (WR) model.
      Single and repeated stimulations were applied to the digital nerve of the left
      forelimb in ponies anaesthetised with isoflurane before, during and after
      intravenous administration of racemic ketamine. Surface electromyographic
      activity was recorded from the deltoid muscle. Higher stimulation intensity was
      required to evoke a reflex during ketamine administration. Furthermore, the
      amplitudes of response to stimulations were significantly and dose-dependently
      depressed and a flattening of the stimulus-response curves was observed. The
      reflex activity recovered partially once the ketamine infusion finished. The
      results demonstrated that the limb WR can be used to quantify the temporal effect
      of ketamine on the sensory-motor processing in ponies anaesthetised with
      isoflurane.

PMID- 19748808
TI  - Uncommon manifestations of neuroborreliosis in children.
AB  - Lyme borreliosis is a tick-borne spirochetal infection which affects the skin,
      joints, heart and nervous system. Children with a neuroborreliosis usually
      present with a facial nerve palsy or aseptic meningitis, but the spectrum also
      includes other rare manifestations. We report four unusual cases of childhood
      neuroborreliosis and show that seizures with regional leptomeningeal enhancement,
      acute transverse myelitis, meningoradiculitis with pain and paraesthesia and
      cranial nerve palsies other than facial nerve palsy can be the leading symptoms
      of children with neuroborreliosis. All children had serological evidence of an
      acute infection with Borrelia burgdorferi, a pleocytosis in the cerebrospinal
      fluid and a complete response to antibiotic treatment. An intrathecal synthesis
      of IgG antibodies was detected in three children. Thus, diagnostic work up in
      children with unusual neurological symptoms should include cerebrospinal fluid
      studies with determination of the white blood cell count and calculation of the
      antibody index against B. burgdorferi.

PMID- 19748809
TI  - Molecular modeling study on the effect of residues distant from the nucleotide
      binding portion on RNA binding in Staphylococcus aureus Hfq.
AB  - Hfq is an abundant RNA-binding bacterial protein that was first identified in E.
      coli as a required host factor for phage Qbeta RNA replication. The pleiotrophic
      phenotype resulting from the deletion of Hfq predicates the importance of this
      protein. Two RNA-binding sites have been characterized: the proximal site which
      binds sRNA and mRNA and the distal site which binds poly(A) tails. Previous
      studies mainly focused on the key residues in the proximal site of the protein. A
      recent mutation study in E. coli Hfq showed that a distal residue Val43 is
      important for the protein function. Interestingly, when we analyzed the sequence
      and structure of Staphylococcus aureus Hfq using the CONSEQ server, the results
      elicited that more functional residues were located far from the nucleotide
      binding portion (NBP). From the analysis seven individual residues Asp9, Leu12,
      Glu13, Lys16, Gln31, Gly34 and Asp40 were selected to investigate the
      conformational changes in Hfq-RNA complex due to point mutation effect of those
      residues using molecular dynamics simulations. Results showed a significant
      effect on Asn28 which is an already known highly conserved functionally important
      residue. Mutants D9A, E13A and K16A depicted effects on base stacking along with
      increase in RNA pore diameter, which is required for the threading of RNA through
      the pore for the post-translational modification. Further, the result of protein
      stability analysis by the CUPSAT server showed destabilizing effect in the most
      mutants. From this study we characterized a series of important residues located
      far from the NBP and provide some clues that those residues may affect sRNA
      binding in Hfq.

PMID- 19748810
TI  - Treatment reduces or stabilizes brain imaging abnormalities in patients with MPS
      I and II.
AB  - BACKGROUND: The mucopolysaccharidoses (MPSs) are a family of lysosomal storage
      disorders caused by impaired glycosaminoglycan degradation. Characteristic brain
      imaging abnormalities are seen in MPS patients. This study aims to determine the
      effects of hematopoietic stem cell transplantation (HSCT) and/or intravenous
      enzyme replacement therapy (ERT) on these abnormalities. METHODS: A retrospective
      chart and brain imaging study review was conducted of MPS types I and II patients
      with brain magnetic resonance imaging (MRI) performed at, and following,
      initiation of treatment. White matter abnormalities, dilated perivascular spaces,
      corpus callosal abnormalities, and ventriculomegaly were scored by three
      independent neuroradiologists blinded to cognitive status, date of treatment
      initiation, and type(s) of treatment. RESULTS: Five patients were identified:
      three patients with MPS I and two with MPS II. Duration of follow-up ranged from
      13 to 51 months. One patient had severe MPS I (genotype W402X/35del12) and
      received ERT followed by HSCT. The remaining patients had ERT only. The other two
      MPS I patients were cognitively normal siblings (genotype P533R/P533R) with an
      intermediate phenotype. One MPS II patient had moderate cognitive impairment
      without regression (genotype 979insAGCA); the other (genotype R8X) had normal
      cognition. There was very little inter-observer variation in MRI scoring. The
      greatest abnormalities for each patient were found at initial MRI. All patients,
      including the ERT-only patients, demonstrated improved or unchanged MRI scores
      following treatment. Severity of white matter abnormalities or dilated
      perivascular spaces did not correlate with cognitive impairment; as such,
      extensive pre-treatment MRI abnormalities were noted in the older, cognitively
      normal MPS I sibling. In comparison, his younger sibling had only mild MRI
      abnormalities at the same age, after receiving 4 years of ERT. CONCLUSIONS: This
      study represents one of the first to document the CNS effects of ERT in MPS
      patients utilizing serial brain MR imaging studies, and raises several important
      observations. Brain MRI abnormalities typically become more pronounced with age;
      initiation of ERT or HSCT reversed or stabilized this trend in the MPS patients
      studied. In addition, earlier initiation of treatment resulted in decreased
      severity of imaging abnormalities. Possible mechanisms for these observations
      include improved cerebrospinal fluid dynamics, reduced central nervous system
      glycosaminoglycan storage via efflux through the blood-brain barrier (BBB),
      repair of damaged BBB, reduction in CNS inflammation, or ERT permeability through
      the BBB.

PMID- 19748811
TI  - Influence of hepatocyte nuclear factor 4alpha (HNF4alpha) gene variants on the
      risk of type 2 diabetes: a meta-analysis in 49,577 individuals.
AB  - BACKGROUND: The nuclear receptor hepatocyte nuclear factor 4alpha (HNF4alpha)
      contributes to the regulation of a large fraction of liver and pancreatic islet
      transcriptomes. AIM: To evaluate the influence of HNF4alpha polymorphisms across
      the entire locus on the occurrence of type 2 diabetes (T2D) by means of a meta
      analysis. METHODS: We evaluated haplotype block structure of HNF4alpha variants
      owing to linkage disequilibrium (LD). From 1455 reports, we evaluated 21
      observational studies. RESULTS: Six haplotype blocks of LD were constructed with
      SNPs with r(2)>0.8; there were also 14 unlinked SNPs. Overall, we included 22,920
      cases and 26.657 controls. Among 17 heterogeneous studies (21,881 cases and
      24,915 controls), including 3 SNPs of P2 promoter region in block 1, we observed
      a significant association with T2D in fixed (OR 0.94, 95%CI: 0.905-0.975,
      p=0.001) and random (OR 0.988, 95%CI: 0.880-0.948, p=0.000012) model. Three
      homogeneous studies were evaluated in block 2 (2684 cases and 2059 controls), and
      a significant association with T2D was also observed: OR: 1.121, 95%CI 1.013
      1.241, p=0.027. Three additional variants were associated with T2D: two intronic
      SNPs (rs4810424: OR: 1.080, 95%CI: 1.010-1.154, p<0.03 and rs3212183: OR: 0.843,
      95%CI: 0.774-0.918, p<0.00009) and one missense variant (rs1800961: OR: 0.770,
      95%CI: 0.595-0.995, p<0.05, 6562 cases and 6723 controls). CONCLUSIONS: In
      addition to HNF4alpha variants in the promoter region, other SNPs may be involved
      on the occurrence of T2D.

PMID- 19748812
TI  - [Knowledge and attitudes on pain management by nurses in surgery and oncology in
      level III hospitals].
AB  - OBJECTIVE: Identify the knowledge and attitudes on pain by nurses in general
      surgery and oncology units in Level III hospitals, and to find out if there are
      any differences between groups. METHOD: A multicentre, observational, analytical
      and cross-sectional study conducted in the general surgery and oncology units in
      5 Spanish level III hospitals. Study subjects were all nurses working in these
      units. We collected demographic variables, as well as employment and training on
      the level of pain. To assess the knowledge and attitudes the Nurses' Knowledge
      and Attitudes Survey Regarding Pain questionnaire was used. RESULTS: Of the 236
      questionnaires delivered, 170 were successfully completed (72%). A total of 96
      nurses (58%) indicated that they had received specific training on pain. A large
      majority, 85% (145) felt that patients should not have pain, and 14.7% (25) said
      it was normal that they should have moderate or intense pain. A total of 93.8%
      (152) were in agreement that the person to assess the intensity of pain more
      accurately is the patient, 46% (74) considered that 10% of patients exaggerated
      the intensity of pain. The majority, 61.9% (52), did not know the equivalence
      between oral and intravenous morphine. The overall median of correct answers, of
      which there was 37 in the questionnaire, was 18 (min=0, max=28), categorized as a
      score of 0 to 10, the median was 5 (min=0, max=8). CONCLUSIONS: The level of
      knowledge that the nurses studied had on pain was not very high. Specific
      training is required and its impact evaluated.

PMID- 19748813
TI  - RBC alloimmunization is an important complication of FFP transfusion: A case
      report of immune anti-D induced by apheresis fresh frozen plasma.
AB  - UK, Germany as well as the Council of Europe recommendation guide have set limits
      of RBC in clinical fresh frozen plasma (FFP), but current transfusion guidelines
      do not get the consensus opinion at recommending the D status of FFP to be
      considered before transfusion. We report a female group A, D- patient with
      cerebrovascular disease who was induced to develop IgG immune anti-D which can be
      detected on the 15th day of hospitalization after the relatively regular time
      interval of transfusion of 1800ml apheresis FFP. Therefore, in making clinical
      decisions to transfuse FFP or apheresis FFP, the best choice is considered as the
      same or compatibility with RhD group, in case Rh immunization can be induced and
      trigger some potential serious problems in future emergent transfusion or
      pregnancy, especially in high incidence of D antigen countries.

PMID- 19748814
TI  - Ecofriendly laccase-hydrogen peroxide/ultrasound-assisted bleaching of linen
      fabrics and its influence on dyeing efficiency.
AB  - This study evaluates the bleaching efficiency of enzymatically scoured linen
      fabrics using a combined laccase-hydrogen peroxide bleaching process with and
      without ultrasonic energy, with the goal of obtaining fabrics with high whiteness
      levels, well preserved tensile strength and higher dye uptake. The effect of the
      laccase enzyme and the combined laccase-hydrogen peroxide bleaching process with
      and without ultrasound has been investigated with regard to whiteness value,
      tensile strength, dyeing efficiency and dyeing kinetics using both reactive and
      cationic dyes. The bleached linen fabrics were characterized using X-ray
      diffraction and by measuring tensile strength and lightness. The dyeing
      efficiency and kinetics were characterized by measuring dye uptake and colour
      fastness. The results indicated that ultrasound was an effective technique in the
      combined laccase-hydrogen peroxide bleaching process of linen fabrics. The
      whiteness values expressed as lightness of linen fabrics is enhanced by using
      ultrasonic energy. The measured colour strength values were found to be slightly
      better for combined laccase-hydrogen peroxide/ultrasound-assisted bleached
      fabrics than for combined laccase-hydrogen peroxide for both reactive and
      cationic dyes. The fastness properties of the fabrics dyed with reactive dye were
      better than those obtained when using cationic dye. The time/dye uptake isotherms
      were also enhanced when using combined laccase-hydrogen peroxide/ultrasound
      assisted bleached fabric, which confirms the efficiency of ultrasound in the
      combined oxidative bleaching process. The dyeing rate constant, half-time of
      dyeing and dyeing efficiency have been calculated and discussed.

PMID- 19748815
TI  - Defining the construct of masters level clinical practice in manipulative
      physiotherapy.
AB  - The study is the first to have explored the behaviours indicative of the
      construct of masters level manipulative physiotherapy clinical practice. An
      exploratory case study was employed, using multiple methods of interviews and
      participant observation, informed by initial documentary analysis. One 'case' of
      a university postgraduate course in manipulative physiotherapy in the UK was
      selected. Purposive sampling identified the participants (clinical tutors and
      students). Data analysis was an iterative process developing inductive categories
      from the data through a constant comparative process. The identified analytic
      categories were subsequently linked to form theoretical propositions. Saturation
      of the data was achieved. Data collection was concurrent with a previously
      reported Delphi study and the findings of each showed convergence. A high level
      of clinical reasoning was identified as the most important behaviour associated
      with the construct for manipulative physiotherapy. This was then subdivided into
      core components of practice; prioritisation for example. This study provides a
      sound basis for future research by affording insight into the construct of
      masters level manipulative physiotherapy clinical practice. Convergence of data
      with the Delphi study supported validation of the construct. The trustworthiness
      of the findings appeared good, and therefore provides justification for use of
      the construct in informing curriculum development at masters level.

PMID- 19748816
TI  - Parental memories shape seeds.
AB  - It is ten years since imprinting was first demonstrated in Arabidopsis, following
      the realization, five years earlier, that some genetic controls of seed
      development did not conform to Mendelian inheritance. Sixteen imprinted genes
      have since been identified in maize and Arabidopsis and these are expressed
      primarily in the endosperm, which nurtures embryo development. Imprinting results
      from the regulation of transcriptional silencing by DNA methylation or by
      Polycomb Group complex-mediated histone methylation. Here we review recent
      studies suggesting that imprinting results from global epigenetic changes that
      occur during female gametogenesis. We also discuss why imprinting has evolved and
      what its biological functions might be.

PMID- 19748817
TI  - Light as a modulator of cognitive brain function.
AB  - Humans are a diurnal species usually exposed to light while engaged in cognitive
      tasks. Light not only guides performance on these tasks through vision but also
      exerts non-visual effects that are mediated in part by recently discovered
      retinal ganglion cells maximally sensitive to blue light. We review recent
      neuroimaging studies which demonstrate that the wavelength, duration and
      intensity of light exposure modulate brain responses to (non-visual) cognitive
      tasks. These responses to light are initially observed in alertness-related
      subcortical structures (hypothalamus, brainstem, thalamus) and limbic areas
      (amygdala and hippocampus), followed by modulations of activity in cortical
      areas, which can ultimately affect behaviour. Light emerges as an important
      modulator of brain function and cognition.

PMID- 19748818
TI  - Herding in humans.
AB  - Herding is a form of convergent social behaviour that can be broadly defined as
      the alignment of the thoughts or behaviours of individuals in a group (herd)
      through local interaction and without centralized coordination. We suggest that
      herding has a broad application, from intellectual fashion to mob violence; and
      that understanding herding is particularly pertinent in an increasingly
      interconnected world. An integrated approach to herding is proposed, describing
      two key issues: mechanisms of transmission of thoughts or behaviour between
      agents, and patterns of connections between agents. We show how bringing together
      the diverse, often disconnected, theoretical and methodological approaches
      illuminates the applicability of herding to many domains of cognition and suggest
      that cognitive neuroscience offers a novel approach to its study.

PMID- 19748819
TI  - Plant 14-3-3 proteins catch up with their mammalian orthologs.
AB  - Members of the eukaryotic 14-3-3 family are highly conserved proteins that have
      been implicated in the modulation of distinct biological processes by
      phosphorylation-dependent protein-protein interactions. In plants, 14-3-3
      mediated regulation of house-keeping proteins such as nitrate reductase and the
      plasma membrane localized H(+)-ATPase has been intensely studied. Recent proteome
      wide approaches have indicated that the plant 14-3-3 interactome is comparable in
      size and functional complexity to its animal counterpart and, furthermore,
      shifted the focus of attention to signal mediators. In this regard, in vivo
      analyses of certain signaling proteins, such as BRASSINAZOLE-RESISTANT 1, a
      transcription factor controlling brassinosteroid responsive gene expression,
      verified an essential role for 14-3-3s in hormonal signal transduction processes.

PMID- 19748820
TI  - Recent advances in systems microbiology.
AB  - Systems biology is a rapidly expanding field fuelled by the 'omics' era coupled
      to several new technological advances that have increased the precision of data
      obtainable, meaning that it is now feasible to obtain quantitative measurements
      from a single cell. The aim of systems biology is to understand the structure,
      dynamics and interactions of whole cells rather than the function of individual
      parts. The challenge now is to use these data in conjunction with modelling
      techniques to extend our knowledge of bacterial systems and to be able to
      experimentally verify in silico predictions.

PMID- 19748821
TI  - Synthesis, characterization and DNA-binding studies of ruthenium(II) mixed-ligand
      complexes containing dipyrido[1,2,5]oxadiazolo[3,4-b]quinoxaline.
AB  - A novel ligand dipyrido[1,2,5]oxadiazolo[3,4-b]quinoxaline (dpoq) and its
      complexes [Ru(bpy)(2)(dpoq)](2+) and [Ru(phen)(2)(dpoq)](2+) (bpy=2,2'
      bipyridine; phen=1,10-phenanthroline) have been synthesized and characterized by
      elemental analysis, electrospray mass spectra and (1)H NMR. The interaction of
      Ru(II) complexes with calf thymus DNA (CT-DNA) was investigated by absorption
      spectroscopy, fluorescence spectroscopy, thermal denaturation and viscosity
      measurements. Results suggest that two Ru(II) complexes bind to DNA via an
      intercalative mode.

PMID- 19748822
TI  - Clinical performances of two real-time PCR assays and bDNA/TMA to early monitor
      treatment outcome in patients with chronic hepatitis C.
AB  - BACKGROUND: Early viral monitoring is essential for the management of treatment
      outcome in patients with chronic hepatitis C. A variety of commercially available
      assays are now available to quantify HCV-RNA in routine clinical practice.
      OBJECTIVES: Compare the clinical results of 3 commercially available assays to
      evaluate the positive predictive value (PPV) and the negative predictive value
      (NPV) of rapid virological response (RVR) at week 4 and early virological
      response (EVR) at week 12. STUDY DESIGN: 287 patients treated with standard care
      regimen combination therapy were studied. HCV-RNA values measured at baseline,
      week 4, week 12 with VERSANT HCV 3.0 Assay (bDNA), and VERSANT HCV-RNA
      Qualitative Assay (TMA) (bDNA/TMA); COBAS Ampliprep/COBAS/TaqMan (CAP/CTM) and
      Abbott m2000sp extraction/m2000rt amplification system (ART). RVR was defined as
      undetectable serum HCV-RNA and EVR as a > OR =2 log decline in baseline viral
      load (BLV). RESULTS: Median (range) BVLs were: 5.585(2.585-6.816), 5.189(2.792
      7.747) and 4.804(2.380-6.580) log(10)IU/ml, with bDNA/TMA, CAP/CTM and ART,
      respectively (p<0.01); RVR was observed in 22%, 30% and 27% of the patients and
      PPVs were 97%, 91% and 94% with bDNA/TMA, CAP/CTM and ART, respectively
      (p=0.317). EVR was observed in 76%, 73% and 67% of the patients and NPVs were
      93%, 83% and 79% with bDNA/TMA, CAP/CTM and ART, respectively (p=0.09).
      CONCLUSIONS: Treatment monitoring should include both detection of serum HCV-RNA
      at week 4 to predict SVR and at week 12 to predict non-SVR. The value of all 3
      assays was similar for evaluating RVR or EVR. Because of viral load discrepancies
      the same assay should be used throughout patient treatment follow-up.

PMID- 19748823
TI  - Quantification of cytomegalovirus DNA levels in intestinal biopsies as a
      diagnostic tool for CMV intestinal disease.
AB  - BACKGROUND: CMV intestinal disease (CMV-ID) is a serious complication in
      immunocompromised patients and mainly diagnosed by clinical, endoscopic and
      histopathologic findings, whereas qualitative CMV-PCR in tissue samples is not
      recommended for diagnosis due to its low positive predictive value (PPV).
      OBJECTIVES: To study the interpretation and diagnostic use of CMV-quantification
      by PCR in intestinal tissue biopsies to recognize CMV-ID. To develop cut-off
      intestinal CMV-loads attributing illness to CMV. STUDY DESIGN: CMV-genome copies
      in 163 biopsies from the lower intestinal tract of immunocompromised patients
      were determined by quantitative real-time PCR, normalized to the cell number, and
      retrospectively compared to histopathological analysis, clinical findings and
      occurrence of CMV-antigenemia. Two cut-off intestinal CMV-loads, cut-off(histo)
      and cut-off(clin), were defined using histopathological or clinical criteria as
      gold standard, respectively. RESULTS: CMV was detected in 32.5% of biopsies with
      a more than six log range of CMV-concentrations (1 x 10(-4)-1.4 x
      10(2)copies/cell). Notably, biopsies with histopathologically or clinically
      confirmed CMV-ID had a significantly higher CMV-load (p<0.001). Cut-off(histo)
      and cut-off(clin) were defined at the intestinal CMV-load of 0.14 and 0.01
      copies/cell, respectively, and improved the PPV. However, cut-off(histo) showed a
      decreased sensitivity for clinically defined CMV-ID cases. Interestingly, many
      patients with CMV-ID showed no concomitant CMV-antigenemia, suggesting a
      localized intestinal CMV-replication. CONCLUSIONS: Quantification of CMV in
      intestinal biopsies is a useful diagnostic tool allowing the definition of cut
      off values that can predict CMV-ID more accurate than qualitative PCR results.
      Further prospective studies have to clarify wether these cut-offs can improve
      diagnostics and treatment of CMV-ID in day-to-day clinical practice.

PMID- 19748824
TI  - CTL escape mutations of core protein are more frequent in strains of HBeAg
      negative patients with low levels of HBV DNA.
AB  - BACKGROUND: Recent studies have suggested that Cytotoxic T lymphocytes (CTL) play
      a key role in eliminating hepatitis B virus (HBV). OBJECTIVES: We aimed to
      investigate the role of mutations in different immune epitopes of hepatitis B
      core antigen (HBcAg) among Iranians with hepatitis B e antigen negative chronic
      hepatitis B (e-CHB), and asymptomatic carriers (ASCs). STUDY DESIGN: Amino acids
      1-150 of HBcAg were characterized for HBV strains from 29 e-CHB patients and 48
      ASCs from Iran. All patients were infected with HBV genotype D and had previously
      been investigated for the presence of pre-core and basic core promoter (BCP)
      mutants. RESULTS: Amino acid mutations of core protein were observed more
      frequently in HBV strains from ASCs than e-CHB patients (p=0.014). Asn(67)
      mutation was mutually exclusive to the combination Ile(66) and Ser(69) (P<0.001).
      Substitutions for Ser(21) and Thr12Ser were associated with lower serum levels of
      HBV DNA (p<0.001). None of the patients with mutations in HLA-A2 CTL epitope, 18
      27, had serum HBV DNA more than 10(5)copies/mL (p<0.001). By multivariate
      analysis, high level (>10(5)copies/mL) of serum HBV DNA was inversely associated
      with the presence of mutations in CTL epitopes of HBc (OR: 0.11, p=0.015), while
      it was directly associated with the presence of promoter double T(1762)A(1764)
      mutations together with G(1757) (OR: 16.87, p=0.004). CONCLUSION: The inverse
      correlation between serum levels of HBV DNA and CTL escape mutations of the core
      protein in HBeAg seroconverted patients, supports the notion that selection of
      CTL escape mutations consolidates the persistence of HBV infection despite
      reducing viral fitness.

PMID- 19748825
TI  - Low resolution electromagnetic tomography analysis of ictal EEG patterns in
      mesial temporal lobe epilepsy with hippocampal sclerosis.
AB  - OBJECTIVE: To investigate the difference in the spatial distribution of scalp
      initial ictal discharge (IID) patterns in mesial temporal lobe epilepsy with
      hippocampal sclerosis (HS-MTLE). METHODS: Scalp ictal EEG data in 22 seizure-free
      patients after temporal lobectomy with amygdalo-hippocampectomy were classified
      as follows: a regular 5-9Hz rhythm with a restricted temporal/subtemporal
      distribution (type 1, 11 patients), or an irregular 2-5Hz rhythm with a
      widespread fronto-temporal distribution (type 2, 11 patients). EEG data were
      fragmented into segments of 1.28s, both at ictal onset and at baseline. The
      LORETA solution of three frequency bands was compared between ictal and baseline
      using statistical non-parametric mapping (p<0.01). RESULTS: The LORETA solution
      of 5-9Hz in type 2 had wider cortical activity in the ipsilateral fronto-temporal
      area, compared to type 1 with activation of the ipsilateral focal mesial and
      lateral temporal regions. The LORETA solution of 10-13Hz in both types showed
      increased activity in the fronto-temporal area, which was wider in type 2 than
      type 1. Increased cortical activity of <5Hz was not observed in type 1, whereas
      increased cortical activity was observed in the bilateral anterior frontal area
      in type 2. CONCLUSIONS: The cortical source distribution in HS-MTLE may depend on
      scalp IID frequency. The neural generators of 5-13Hz may be important for the
      formation of the ictal onset zone in both ictal patterns. SIGNIFICANCE: Spatial
      distributions in HS-MTLE patients differ with scalp IID frequency.

PMID- 19748826
TI  - Corticomotoneuronal dysfunction: a process specific to amyotrophic lateral
      sclerosis?

PMID- 19748827
TI  - Cortical correlates of the basic and first harmonic frequency of Parkinsonian
      tremor.
AB  - OBJECTIVE: It has been hypothesized that the basic and first harmonic frequency
      of Parkinsonian tremor are somewhat independent oscillations the biological basis
      of which remains unclear. METHODS: We recorded 64-channel EEG in parallel with
      EMG of the forearm muscles most affected by rest tremor in 21 PD patients. EMG
      power spectrum, corticomuscular coherence spectra and EEG power spectra for each
      EEG electrode were calculated. The dynamics of the coherence and relative EMG and
      EEG power at the basic (tremor) frequency were calculated by a sliding,
      overlapping window analysis. Corticomuscular delays and direction of interaction
      were analysed by the maximizing coherence method for narrow band signals.
      RESULTS: The contralateral EEG electrodes with maximal coherence were different
      for the basic and first harmonic frequency. The dynamical coherence curves showed
      non-parallel time courses for the two frequencies. The mean EEG-EMG and EMG-EEG
      delays were all around 15-20ms but significantly longer for the first harmonic
      than for the basic frequency. CONCLUSIONS: Our data indicate different cortical
      representations and corticomuscular interaction of the basic and first harmonic
      frequencies of Parkinsonian tremor. SIGNIFICANCE: Separate central generators
      seem to contribute to the tremor via different pathways. Further studies on this
      complex tremor network are warranted.

PMID- 19748828
TI  - EEG differences in children between eyes-closed and eyes-open resting conditions.
AB  - OBJECTIVE: Recent work on arousal vs. activation in adults showed that skin
      conductance levels (SCLs) increased, and global alpha levels decreased, from eyes
      closed to eyes-open resting baseline conditions. This study explored whether
      similar effects occur in children. METHODS: EEG activity was recorded from 30
      children aged 8-12 years during counterbalanced eyes-closed and eyes-open resting
      conditions; SCL was measured as an index of arousal. RESULTS: SCLs were
      negatively correlated with mean alpha levels in the eyes-closed condition, and
      increased significantly from eyes-closed to eyes-open. Reductions were found in
      across-scalp mean absolute delta, theta, alpha, and beta from eyes-closed to eyes
      open. Topographic changes were evident in all bands except alpha. CONCLUSIONS:
      Results confirm the use of mean alpha level as a measure of resting-state arousal
      under eyes-closed and eyes-open conditions. Focal changes in the other bands
      suggest that these reflect differences in activation, rather than the simple
      increase in arousal shown in alpha. SIGNIFICANCE: This child study confirms the
      generality of eyes-closed vs. eyes-open non-alpha EEG measures differing in mean
      power levels and topography, the latter indicating brain activity related to
      visual processing. Such differences should be considered when evaluating EEG
      research, and in choosing baseline conditions for different paradigms.

PMID- 19748829
TI  - Prospects for the next anti-Pseudomonas drug.
AB  - Pseudomonas aeruginosa is one of the most dreaded Gram-negative bacterial
      pathogens in hospitals. Not only it is among the most frequently isolated Gram
      negative organisms in bloodstream and wound infections, pneumonia, intra
      abdominal-sepsis and urogenital-sepsis, but also it is frequently found in
      patients with comorbid illnesses and compromised by in-dwelling catheters, tubes
      and surgery where mortality rates of more than 60% have been reported. Besides
      its intrinsic resistance to a number of widely used antibiotics, Pseudomonas also
      managed to acquire resistance via additional mechanisms, including target
      mutations, increased expression of efflux pumps and of antibiotic-degrading
      enzymes. Taken together, the increased incidence in certain types of infections,
      the increased use of invasive devices in the hospital as well as the increased
      frequency of multi-resistant Pseudomonas strains, have clearly led to a shortage
      of treatment options for nosocomial Pseudomonas infections. Even the recommended
      combination therapy of an antibiotic of the beta-lactam class together with an
      aminoglycoside or a fluoroquinolone, is no longer always successful and sometimes
      a polymyxin has to be given as last resort. Despite growing concerns of
      clinicians and medical societies about the very limited number of novel drugs in
      the pipeline to fight multi-resistant Pseudomonas strains, only a very small
      number of novel anti-Pseudomonas drugs are currently in late stage of pre
      clinical or clinical development. However, and possibly as a reflection of the
      magnitude of the problem, quite a variety of approaches are being pursued. Among
      these are next-generation analogues of successful antibiotic classes (e.g. novel
      beta-lactams and combinations of novel beta-lactamase inhibitors with known
      penicillins or cephalosporins), antibodies, phages and selective peptides. It is
      to be hoped that a number of these novel drugs will show clinical utility and
      reach the market over the next 6-10 years.

PMID- 19748830
TI  - Lack of sensitivity to readmission: a grounded theory study for explaining the
      process of readmitting patients suffering from congestive heart failure.
AB  - BACKGROUND: Readmission due to congestive heart failure is a global problem
      during the recent decades; however, little is known about the process of
      readmission in these patients. AIM: To clarify the readmission process of
      patients suffering from congestive heart failure in two large referral hospitals
      in Tehran, Iran. METHOD: A grounded theory approach was utilized. 42 experienced
      patients, families, nurses and cardiologists participated in the study. Data
      analysis was carried out over a period of 12months (November 2007 to November
      2008). RESULTS: The main concern of participants was "managing the acute
      problems" of disease. The process of readmission begins with "concentrating on
      the concern". So, all the participants neglected the patient readmission. Having
      managed the acute problems, the patients were discharged without a "comprehensive
      context oriented discharge planning" leading to their return to community without
      preparation or supporting system. This results in "traditional self-treatment"
      owing to unhealthy behaviors which brings about the readmission of patients.
      Neglecting or "lack of sensitivity to readmission" was presented as the core
      variable. CONCLUSION: In order to control readmission, we recommend those in
      charge of policy-making for public health to pay particular attention to this
      variable and taking step such as sensitizing people concerned.

PMID- 19748831
TI  - Classification for high-throughput data with an optimal subset of principal
      components.
AB  - High-throughput data have been widely used in biological and medical studies to
      discover gene and protein functions. Due to the high dimensionality, principal
      component analysis (PCA) is often involved for data dimension reduction. However,
      when a few principal components (PCs) are selected for dimension reduction or
      considered for dimension determination, they are typically ranked by their
      variances, eigenvalues. However, this approach is not always effective in
      subsequent multivariate analysis, particularly classification. To maximize
      information from data with a subset of the components, we apply a different
      ranking criterion, canonical variate criterion, which considers within- and
      between-group variance rather than total variance in the classical criterion.
      Four prevalent classification methods are considered and compared using leave-one
      out cross-validation. These methods are illustrated with three real high
      throughput data sets, two microarray data sets and a nuclear magnetic resonance
      spectra data set.

PMID- 19748832
TI  - Down-regulation of TIPE2 mRNA expression in peripheral blood mononuclear cells
      from patients with systemic lupus erythematosus.
AB  - Breakdown of immune homeostasis contributes to the pathogenesis of systemic lupus
      erythematosus (SLE). Tumor necrosis factor alpha induced protein-8 like-2 (TIPE2)
      is a very recently identified immune homeostasis maintaining gene. We wondered
      whether TIPE2 is associated with SLE. We examined the mRNA expression levels of
      TIPE2 and myxoma resistance protein (MX) 1 (one of type I interferon inducible
      genes) in peripheral blood mononuclear cells (PBMC) from 39 SLE patients and 35
      healthy controls by real-time reverse transcription-polymerase chain reaction
      analysis (RT-PCR). The TIPE2 mRNA expression was significantly down-regulated in
      SLE patients compared with healthy controls (P=0.0004), while the MX1 mRNA
      expression was increased in SLE patients compared with healthy controls
      (P=0.0031). Furthermore, the TIPE2 mRNA expression levels negatively correlate
      with the SLE disease activity index (SLEDAI) (r=-0.5016, P=0.0011) and the MX1
      mRNA expression levels (r=-0.8083, P<0.0001) in all the SLE patients. These
      results indicate that decreased expression of TIPE2 gene is closely associated
      with SLE and suggest an important role for TIPE2 gene in the pathogenesis of SLE.

PMID- 19748833
TI  - Can cost utility evaluations inform decision making about interventions for low
      back pain?
AB  - BACKGROUND CONTEXT: Low back pain (LBP) is associated with high health-care
      utilization and lost productivity. Numerous interventions are routinely used,
      although few are supported by strong evidence. Cost utility analyses (CUAs) may
      be helpful to inform decision makers. PURPOSE: To conduct a systematic review of
      CUAs of interventions for LBP. STUDY DESIGN: Systematic review. METHODS: A search
      strategy combining medical subject headings and free text related to LBP and
      health economic evaluations was executed in MEDLINE. Cost utility analyses
      combined with randomized controlled trials for LBP were included. Studies that
      were published before 1998, non-English, decision analyses, and duplicate reports
      were excluded. Search results were evaluated by two reviewers, who extracted data
      independently related to clinical study design, economic study design, direct
      cost components, utility results, cost results, and CUA results. RESULTS: The
      search produced 319 citations, and of these 15 met eligibility criteria. Most
      were from the United Kingdom (n=8), published in the past 3 years (n=12), studied
      chronic LBP or radiculopathy (n=13), and had a follow-up >12 months (n=13).
      Combined, there were 33 study groups who received a mean 2.1 interventions, most
      commonly education (n=17), exercise therapy (n=13), spinal manipulation therapy
      (n=7), surgery (n=7), and usual care from a general practitioner (n=7). Mean
      baseline utility was 0.57, improving to 0.67 at follow-up; the mean difference in
      utility improvement between study groups was 0.04. Based on available data and
      converted to US dollars, the cost per quality-adjusted life year ranged from $304
      to 579,527 dollars, with a median of 13,015 dollars. CONCLUSIONS: Few CUAs were
      identified for LBP, and there was heterogeneity in the interventions compared,
      direct cost components measured, indirect costs, other methods, and results.
      Reporting quality was mixed. Currently published CUAs do not provide sufficient
      information to assist decision makers. Future CUAs should attempt to measure all
      known direct cost components relevant to LBP, estimate indirect costs such as
      lost productivity, have a follow-up period sufficient to capture meaningful
      changes, and clearly report methods and results to facilitate interpretation and
      comparison.

PMID- 19748834
TI  - Use of serial CT imaging for the quality assurance of MammoSite therapy.
AB  - PURPOSE: As experience with the MammoSite device for accelerated partial breast
      irradiation (APBI) has increased, more centers are starting to use three
      dimensional (3D) treatment planning to generate plans with multiple nonequally
      weighted dwell positions. This report presents the use of serial computed
      tomography (CT) imaging, in addition to planar or ultrasound imaging, for the
      quality assurance of an APBI treatment using the elliptical MammoSite. METHODS
      AND MATERIALS: CT images of a patient implanted with a 4cmx6cm elliptical
      MammoSite balloon were acquired. A treatment plan using multiple, nonequally
      weighted dwells was generated and delivered on Day 1 of a 10-fraction, twice
      daily treatment. Before morning treatments on Days 2-5, the patient was reimaged
      on CT. Treatment plans on repeat CTs were generated two ways: using the decay
      corrected plan from Day 1 (unadapted) vs. modifying the plan to account for
      changes in implant geometry (adapted). Adapted and unadapted plans on repeat CTs
      were compared with one another, and to the Day 1 plan. RESULTS: The use of
      unadapted plans led to increased doses to normal tissues, particularly the skin.
      Adaptive planning on the repeat CTs was effective for maintaining acceptable
      dosimetry throughout treatment. CONCLUSIONS: Serial CT imaging was shown to
      provide a useful tool for the quality assurance of an elliptical balloon implant
      during the course of treatment. Serial CT imaging, as opposed to planar or
      ultrasound imaging, was necessary to evaluate skin dose and to facilitate
      adaptation of the treatment plan to satisfy limits for skin dose.

PMID- 19748835
TI  - Enteric co-innervation of esophageal striated muscle fibers: a phylogenetic
      study.
AB  - Enteric co-innervation of striated muscle fibers in the esophagus occurs in
      several mammalian species including humans. However, the functional significance
      is still unknown. Phylogenetic data may be instrumental in gaining further
      insight. We examined the bat Glossophaga soricina and the shrew Suncus murinus as
      representatives for phylogenetically old mammals. As ruminants the antelope
      Tragelaphus imberbis, the he-goat Capra falconeri and the sheep Ovis aries were
      selected. As non-mammals the clawed frog Xenopus laevis as representative for the
      taxon amphibian and the rainbow trout Oncorhynchus mykiss as representative for
      the taxon fish were included. Histochemistry for nicotinamide adenine
      dinucleotide phosphate-diaphorase and acetylcholinesterase as well as
      immunofluorescence for vasoactive intestinal peptide and alpha-bungarotoxin were
      used to demonstrate enteric nerve fibers and motor endplates, respectively. Motor
      endplates were associated with enteric nerve fibers in all species investigated,
      although the rates of co-innervation varied from approximately 10 to 20% in
      shrew, antelope, he-goat, frog and fish, approximately 40% in bat to nearly 90%
      in sheep. These results demonstrate that enteric co-innervation, in spite of
      varying co-innervation rates, is conserved through vertebrate evolution, and
      underline the significance of this newly discovered innervation component.

PMID- 19748837
TI  - DNA polymerase beta and PARP activities in base excision repair in living cells.
AB  - To examine base excision repair (BER) capacity in the context of living cells, we
      developed and applied a plasmid-based reporter assay. Non-replicating plasmids
      containing unique DNA base lesions were designed to express luciferase only after
      lesion repair had occurred, and luciferase expression in transfected cells was
      measured continuously during a repair period of 14 h. Two types of DNA lesions
      were examined: uracil opposite T reflecting repair primarily by the single
      nucleotide BER sub-pathway, and the abasic site analogue tetrahydrofuran (THF)
      opposite C reflecting repair by long-patch BER. We found that the repair capacity
      for uracil-DNA in wild type mouse fibroblasts was very strong, whereas the repair
      capacity for THF-DNA, although strong, was slightly weaker. Repair capacity in
      DNA polymerase beta (Pol beta) null cells for uracil-DNA and THF-DNA was reduced
      by approximately 15% and 20%, respectively, compared to that in wild type cells.
      In both cases, the repair deficiency was fully complemented in Pol beta null
      cells expressing recombinant Pol beta. The effect of inhibition of poly(ADP
      ribose) polymerase (PARP) activity on repair capacity was examined by treatment
      of cells with the inhibitor 4-amino-1,8-naphthalimide (4-AN). PARP inhibition
      decreased the repair capacity for both lesions in wild type cells, and this
      reduction was to the same level as that seen in Pol beta null cells. In contrast,
      4-AN had no effect on repair in Pol beta null cells. The results highlight that
      Pol beta and PARP function in the same repair pathway, but also suggest that
      there is repair independent of both Pol beta and PARP activities. Thus, before
      the BER capacity of a cell can be predicted or modulated, a better understanding
      of Pol beta and PARP activity-independent BER pathways is required.

PMID- 19748836
TI  - Neurotrophins and target interactions in the development and regulation of
      sympathetic neuron electrical and synaptic properties.
AB  - The electrical and synaptic properties of neurons are essential for determining
      the function of the nervous system. Thus, understanding the mechanisms that
      control the appropriate developmental acquisition and maintenance of these
      properties is a critical problem in neuroscience. A great deal of our
      understanding of these developmental mechanisms comes from studies of soluble
      growth factor signaling between cells in the peripheral nervous system. The
      sympathetic nervous system has provided a model for studying the role of these
      factors both in early development and in the establishment of mature properties.
      In particular, neurotrophins produced by the targets of sympathetic innervation
      regulate the synaptic and electrophysiological properties of postnatal
      sympathetic neurons. In this review we examine the role of neurotrophin signaling
      in the regulation of synaptic strength, neurotransmitter phenotype, voltage-gated
      currents and repetitive firing properties of sympathetic neurons. Together, these
      properties determine the level of sympathetic drive to target organs such as the
      heart. Changes in this sympathetic drive, which may be linked to dysfunctions in
      neurotrophin signaling, are associated with devastating diseases such as high
      blood pressure, arrhythmias and heart attack. Neurotrophins appear to play
      similar roles in modulating the synaptic and electrical properties of other
      peripheral and central neuronal systems, suggesting that information provided
      from studies in the sympathetic nervous system will be widely applicable for
      understanding the neurotrophic regulation of neuronal function in other systems.

PMID- 19748838
TI  - Simultaneous and sensitive measurement of nicotine, cotinine, trans-3'
      hydroxycotinine and norcotinine in human plasma by liquid chromatography-tandem
      mass spectrometry.
AB  - An LC-MS/MS method for the simultaneous quantification of nicotine, cotinine,
      trans-3'-hydroxycotinine and norcotinine in human plasma was developed and fully
      validated. Potential endogenous and exogenous interferences were extensively
      evaluated and limits of quantification were determined by decreasing analyte
      concentration. Analytical ranges were 1-500 ng/mL for nicotine and cotinine, 5
      500 ng/mL for trans-3'-hydroxycotinine and norcotinine. Mean intra- and inter
      assay analytical recoveries were between 101.9 and 116.8%, and intra- and inter
      assay imprecision were less than 11% RSD for all analytes: parameters were
      evaluated at three different concentrations across the linear range of the assay.
      Extraction efficiency was > or = 70% for all analytes. This validated method is
      useful for the determination of nicotine and metabolites in human plasma to
      support research on the role of nicotine biomarkers on neuronal systems mediating
      cognitive and affective processes and to differentiate active, passive and
      environmental exposure.

PMID- 19748839
TI  - The growth of obesity and technological change.
AB  - This paper presents a dynamic theory of body weight and develops its
      implications. We argue that technological change has induced weight growth by
      making home- and market-production more sedentary and by lowering food prices
      through agricultural innovation. In addition, we illustrate that, while exercise
      and food intake are complements, reductions in exercise will always raise optimal
      body weight, as will increases in food intake. We also characterize how body
      weight varies with income, both within a country, and across countries. Within a
      country, income may have an inverted U-shaped relationship with body weight, due
      to the offsetting effects of the demand for food, and the demand for an ideal
      body weight. This can have important implications for the body weight impacts of
      public transfer programs. Across countries, however, mean weight is likely to be
      higher in richer countries. Finally, we present descriptive empirical evidence
      that illustrates the inverted U-shaped relationship between body weight and
      income in US males, and suggests the importance of secular trends in weight gain,
      which are consistent with the impacts of broad-based technological changes.

PMID- 19748840
TI  - [Combined antifungal therapy. Treatment success in a case of mural endocarditis
      due to Candida glabrata].

PMID- 19748841
TI  - Smoking still harms those around you: a cigarette burn to a child's eye.

PMID- 19748842
TI  - Simulated central face transplantation: age consideration in matching donors and
      recipients.

PMID- 19748843
TI  - [Guidelines for vitamin D prescription in dialysis patients].
AB  - The vitamin D hormonal system is involved in the regulation of more than 800
      genes. Vitamin D deficiency, which is evaluated on the basis of the serum level
      of 25-hydroxycholecalciferol (25[OH]D), is frequently observed in the general
      population, particularly in patients with chronic kidney disease (CKD). Vitamin D
      deficiency is associated with an increased risk of falls and fracture and also
      with diabetes, malignancies, autoimmune diseases, depression and mortality.
      Furthermore, CKD is accompanied by a decrease in the renal production of 1,25
      dihydroxycholecalciferol (1,25[OH](2)D). Such deficiencies have also been
      implicated in the pathophysiology of secondary hyperparathyroidism. Currently,
      vitamin D supplementation is not recommended in stage 5 CKD. However, since there
      is also significant extra-renal production of 1,25(OH)(2)D this would appear to
      be in favour of vitamin D treatment. We describe the disturbances of vitamin D
      metabolism occurring in CKD and discuss the advantages and the potential toxicity
      risk of vitamin D supplementation as well as the optimal serum 25[OH]D level. We
      then present the pharmacological properties of the various medicinal forms of
      vitamin D derivates and suggest therapeutic guidelines for supplementation with
      25(OH)D(3) or cholecalciferol. We also examine existing guidelines for the
      administration of active 1-alpha-hydroxylated vitamin D. Despite the absence of
      strong scientific support by randomized controlled intervention studies, vitamin
      D supplementation should be considered in patients with CKD stages 4-5D having
      vitamin D insufficiency or deficiency, for the prevention of secondary
      hyperparathyroidism and for other potential benefits owing to its pleiotropic
      effects.

PMID- 19748844
TI  - Stroke in under-75-year-olds: expectations, concerns and needs.
AB  - Most studies of functional outcomes in hemiplegic stroke patients use standard
      disability rating scales (such as the Barthel Index). However, planning the
      allocation of assistance and resources requires additional information about
      these patients' expectations and needs. AIMS OF THE STUDY: To assess functional
      independence in daily living and house holding, changes in home settings, type of
      technical aid and human helps, and expectations in hemiplegic patients 1 to 2
      years after the stroke. METHODS: Sixty-one out of 94 patients admitted to the
      neurovascular unit of French university hospital for a first-ever documented
      stroke were consecutively enrolled. The study was restricted to patients under
      75, since patients over 75 do not follow the same care network. Patients were
      examined at their homes or interviewed by phone 17 months (on average) after the
      stroke. Standard functional assessment tools (such as the Barthel Index and the
      instrumental activities of daily living [IADL] score) were recorded, along with
      descriptions of home settings and instrumental and human help. Lastly, patients
      and caregivers were asked to state their expectations and needs. RESULTS:
      Although only one person was living in a nursing home after the stroke, 23 (34%)
      of the other interviewees had needed to make home adjustments or move home. Seven
      patients (11%) were dependent in terms of the activities of daily living (a
      Barthel Index below 60) and 11 (18%) had difficulty in maintaining domestic
      activities and community living (an IADL score over 10). Although the remaining
      patients had made a good functional recovery, 23 were using technical aids and 28
      needed family or caregiver assistance, including 23 patients with full functional
      independence scores. Twenty-five patients (42%) were suffering from depression as
      defined by the diagnosis and statistical manual of mental disorders (4th edition,
      text revision, DSM IV-R). The patients' prime concerns were related to recovery
      of independence, leisure activities and financial resources. Family members'
      expectations related to the complexity of administrative matters, lack of
      information and the delay in service delivery. DISCUSSION AND CONCLUSION: In
      under-75 hemiplegic stroke patients, high scores on standard disability rating
      scales do not always mean that no help is required.

PMID- 19748845
TI  - An effect from anticipation also in hereditary nonpolyposis colorectal cancer
      families without identified mutations.
AB  - Optimal prevention of hereditary cancer is central and requires initiation of
      surveillance programmes and/or prophylactic measures at a safe age. Anticipation,
      expressed as an earlier age at onset in successive generations, has been
      demonstrated in hereditary nonpolyposis colorectal cancer (HNPCC). We
      specifically addressed anticipation in phenotypic HNPCC families without disease
      predisposing mismatch repair (MMR) defects since risk estimates and age at onset
      are particularly difficult to determine in this cohort. The national Danish HNPCC
      register was used to identify families who fulfilled the Amsterdam criteria for
      HNPCC and showed normal MMR function and/or lack of disease-predisposing MMR gene
      mutation. In total, 319 cancers from 212 parent-child pairs in 99 families were
      identified. A paired t-test and a bivariate statistical model were used to assess
      anticipation. Both methods demonstrated an effect from anticipation with cancer
      diagnosed mean 11.4 years (t-test, p<0.0001) and mean 5.9 (bivariate model,
      p=0.02) years earlier in children than in parents. This observation suggests that
      anticipation may apply also to families without identified mutations and serves
      as a reminder to initiate surveillance programmes at young age also in HNPCC
      families with undefined genetic causes.

PMID- 19748846
TI  - Can older women be motivated to attend for their final Papanicolaou tests? The
      use of targeted and general personalised reminder letters.
AB  - BACKGROUND: Australian guidelines allow women to cease having Papanicolaou (Pap)
      tests at the age of 70, providing they have had two negative smears in the
      previous 5 years. In Victoria, a standard reminder letter system is in place and
      women receive one reminder letter 27 months after their last Pap test. METHODS: A
      targeted letter informed by qualitative research was developed to specifically
      encourage older women to have a final Pap test. The Victorian Cervical Cytology
      Registry (VCCR) was used to identify 15,000 women aged 65-69 who had not had a
      Pap test for at least 3 years and up to 17 years. Women were randomly allocated
      to receive either no letter (control group), the targeted letter or a personally
      addressed general reminder letter. RESULTS: At 11 weeks follow-up, 4.3% of women
      (CI 3.7-4.8%) who received the targeted letter had attended for a Pap test
      compared with 4.7% (CI 4.1-5.3%) of those receiving the general letter and 1.6%
      (CI 1.2-1.9%) of the control group. Effectiveness was limited to women whose test
      was no more than 10 years overdue, and was particularly strong for those whose
      test was 3-5 years overdue. CONCLUSIONS: This suggests that a reminder letter was
      effective, but that targeting the information in the letter did not further
      improve screening attendance. A second reminder letter sent to women before their
      Pap test is more than 5 years overdue has potential for increasing the number of
      women attending for screening.

PMID- 19748847
TI  - Glutathione S-transferase polymorphisms and survival in African-American and
      white colorectal cancer patients.
AB  - BACKGROUND: Glutathione S-transferase (GST) enzymes are involved in electrophile
      detoxification. The authors investigated the association between GST genotype and
      survival in a racially diverse, population-based cohort of colorectal cancer
      (CRC) patients followed for a median of 9.6 years. METHODS: Interviews were
      conducted with 315 African-American and White CRC patients in Connecticut, 1987
      1991. Tumor tissue (n=197) was later retrieved from hospital of diagnosis and
      assayed using multiplex PCR (GSTM1 and GSTT1) and PCR and RFLP analysis (GSTP1).
      Cox proportional hazards models provided adjusted hazard ratios (HR) and 95%
      confidence intervals (CI). RESULTS: Individuals with Ile/Val or Val/Val GSTP1
      genotypes had a decreased risk of death (multivariate adjusted HR=0.72, 95% CI:
      0.48, 1.09) relative to those with wild type (Ile/Ile). Among those who received
      chemotherapy, this benefit was more pronounced (HR=0.35, 95% CI: 0.16, 0.79); the
      interaction of reduced function GSTP1 genotype and chemotherapy was significant
      (P=0.05). GSTM1 and GSTT1 genotype were not associated with survival. GSTM1,
      GSTT1, and GSTP1 genotype did not vary by race and did not contribute
      significantly to the survival disadvantage observed in African-Americans.
      CONCLUSIONS: In summary, GSTP1 genotype may play a role in CRC survival in
      African-Americans and Whites, particularly among those who receive chemotherapy.

PMID- 19748848
TI  - Epidemiological composition, clinical and treatment characteristics of the
      patient cohort of the German Competence Network for HIV/AIDS.
AB  - OBJECTIVE: As its central basis for research, the Competence Network for HIV/AIDS
      (KompNet) established a nationwide cohort study on HIV-positive patients being in
      medical care in Germany. In this paper, we describe the epidemiological
      composition, and clinical as well as treatment characteristics of the KompNet
      cohort over time. METHODS: The KompNet cohort is an open, retrospective and
      prospective, multi-center, disease-specific and nationwide cohort study that
      started gathering data in June 2004. Semiannually, follow up visits of the
      patients are documented, covering a wide range of clinical and sociodemographic
      data. At enrollment and three years afterwards, an EDTA-sample is taken; a serum
      sample is taken at every follow up. RESULTS: As of 20.10.2008, a total of 15,541
      patients were enrolled by 44 documenting sites. In September 2007, the cohort
      size was reduced to ten outpatient clinics and fifteen private practitioners,
      covering a total of 9,410 patients. The documentation of these patients comprised
      24,117 years of follow up-time since enrollment (mean: 2.6 years), 62,862 person
      years inclusive data documented retrospectively on course of HIV-infection and
      antiretroviral therapy (ART, mean: 6.7 years). Due to the short period of
      recruitment till now, rates of death (0.3%-0.8%) and losses to follow up (1.1%
      5.5%) were low. 84.9% of patients were men. Main risk of transmission was sex
      between men (MSM: 62.9%). Mean age was 45 years. About two third of patients were
      classified as CDC-stage B or C. Therapy regimens of currently treated patients
      complied with recent guidelines. Trends of mean CD4 cell count/microl regarding
      the initial therapy and concerning the population under treatment reflected the
      developments and the changing standards of antiretroviral therapy over time.
      CONCLUSION: The KompNet cohort covers about a quarter of all patients estimated
      as being under treatment in Germany. Its composition can be accounted
      approximately representative for the situation of clinical care and treatment in
      the scope of HIV/AIDS in Germany. Therefore, it is an important instrument for
      measuring the course of HIV/AIDS, the reality of use of antiretroviral therapy
      and its clinical and psychosocial outcomes in Germany.

PMID- 19748849
TI  - Gene expression of circulating tumour cells in breast cancer patients.
AB  - BACKGROUND: The diagnostic tools to predict the prognosis in patients suffering
      from breast cancer (BC) need further improvements. New technological achievements
      like the gene profiling of circulating tumour cells (CTC) could help identify new
      prognostic markers in the clinical setting. Furthermore, gene expression patterns
      of CTC might provide important informations on the mechanisms of tumour cell
      metastasation. MATERIALS AND METHODS: We performed realtime-PCR and multiplex-PCR
      analyses following immunomagnetic separation of CTC. Peripheral blood (PB)
      samples of 63 patients with breast cancer of various stages were analyzed and
      compared to a control group of 14 healthy individuals. After reverse
      transcription, we performed multiplex PCR using primers for the genes ga733.3,
      muc-1 and c-erbB2. Mammaglobin1, spdef and c-erbB2 were analyzed applying
      realtime-PCR. RESULTS: ga733.2 overexpression was found in 12.7% of breast cancer
      cases, muc-1 in 15.9%, mgb1 in 9.1% and spdef in 12.1%. In this study, c-erbB2
      did not show any significant correlation to BC, possibly due to a highly ambient
      expression. Besides single gene analyses, gene profiles were additionally
      evaluated. Highly significant correlations to BC were found in single gene
      analyses of ga733.2 and muc-1 and in gene profile analyses of ga733.3*muc-1 and
      GA7 ga733.3*muc-1*mgb1*spdef. CONCLUSION: Our study reveals that the single genes
      ga733.3, muc-1 and the gene profiles ga733.3*muc-1 and ga733.3*3muc-1*mgb1*spdef
      can serve as markers for the detection of CTC in BC. The multigene analyses found
      highly positive levels in BC patients. Our study indicates that not single gene
      analyses but subtle patterns of multiple genes lead to rising accuracy and low
      loss of specificity in detection of breast cancer cases.

PMID- 19748850
TI  - Estrogen exposure, obesity and thyroid disease in women with severe pulmonary
      hypertension.
AB  - Severe pulmonary hypertension is a lethal group of disorders which preferentially
      afflicts women. It appears that in recent years the patient profile has shifted
      towards older, obese, and postmenopausal women, suggesting that endocrine factors
      may be important. Several studies have revealed an increased prevalence of
      thyroid disease in these patients, but no studies have evaluated for a
      coexistence of endocrine factors. In particular, no studies have attempted to
      evaluate for concurrent thyroid disease, obesity and long-term estrogen exposure
      in patients. 88 patients attending the Pulmonary Hypertension Association 8th
      International meeting completed a questionnaire and were interviewed. Information
      was collected regarding reproductive history, height, weight, and previous
      diagnosis of thyroid disease. 46% met criteria for obesity. 41% reported a
      diagnosis of thyroid disease. 81% of women reported prior use of hormone therapy.
      70% reported greater than 10 years of exogenous hormone use. 74% of female
      patients reported two or more of potentially disease modifying endocrine factors
      (obesity, thyroid disease or estrogen therapy). The coexistent high prevalence in
      our cohort of exogenous estrogen exposure, thyroid disease and obesity suggests
      that an interaction of multiple endocrine factors might contribute to the
      pathogenesis of pulmonary hypertension and may represent epigenetic modifiers in
      genetically-susceptible individuals.

PMID- 19748851
TI  - Thoracic outlet syndrome: do we have clinical tests as predictors for the outcome
      after surgery?
AB  - OBJECTIVE: Thoracic outlet syndrome (TOS) is a clinical phenomenon resulting from
      compression of the neurovascular structures at the superior aperture of the
      thorax which presents with varying symptoms. Regarding to the varying symptoms,
      the diagnosis of TOS seems to be a challenge and predictors for the outcome are
      rare. The purpose of this study was therefore to analyze the different clinical
      examinations and tests relative to their prediction of the clinical outcome
      subsequent to surgery. METHODS: During a period of five years, 56 patients were
      diagnosed with TOS. Medical history, clinical tests, operative procedure and
      complications were recorded and analysed. Mean follow-up of the patients was 55.6
      +/- 45.5 months, median age of the patients was 36.4 +/- 12.5 years. RESULTS:
      Different clinical tests for TOS showed an acceptable sensitivity overall, but a
      poor specificity. A positive test was not associated with a poor outcome.
      Analyses of the systolic blood pressure before and after exercise showed, that a
      distinct decrease in blood pressure of the affected side after exercises was
      associated with a poor outcome (p = 0.0027). CONCLUSIONS: Clinical tests for TOS
      show a good sensitivity, but a poor specificity and cannot be used as predictors
      for the outcome. A distinct decrease in blood pressure of the affected side after
      exercises was associated with poor outcome and might be useful to predict the
      patients' outcome.

PMID- 19748852
TI  - Reliability of limb alignment measurement for high tibial osteotomy with a
      navigation system.
AB  - OBJECTIVE: High tibial osteotomy (HTO) is one treatment option for young and
      active patients with unicompartmental osteoarthritis. The success of this
      procedure substantially depends on the degree of correction of the mechanical
      axis. Computer-assisted navigation systems are believed to improve the precision
      of axis correction through intraoperative real-time monitoring. This study
      investigates the accuracy of limb alignment measurements with a navigation system
      on a cadaver specimen. MATERIALS AND METHODS: The measurements were performed on
      a well-preserved cadaver specimen with a mechanical leg axis of 4 degrees varus.
      Data was collected during the HTO workflow. Repeated serial measurements were
      undertaken by four different surgeons. After these measurements, different
      landmarks were deliberately set at the wrong place to examine the influence of
      mistakes during registration. RESULTS: There was a high intra- and interobserver
      reliability with a mean mechanical leg axis of 3.9 degrees +/- 0.7 degrees and a
      mean error of 0.6 degrees. The grossly incorrect placement of landmarks for knee
      and ankle center resulted in an incorrect mechanical leg axis of 1 degrees valgus
      up to 10 degrees varus. CONCLUSION: The computer-assisted navigation system
      provided precise information about the mechanical leg axis, irrespective of the
      observer's experience.

PMID- 19748853
TI  - Banding pattern indicative of echinococcosis in a commercial cysticercosis
      Western blot.
AB  - OBJECTIVE: A commercial cysticercosis Western blot was evaluated for serological
      cross-reactivity of sera from patients with alveolar (AE) and cystic
      echinococcosis (CE). METHODS: A total of 161 sera were examined, including 31
      sera from AE-patients, 11 sera from CE- patients, 9 sera from patients with other
      parasitic diseases and 109 sera from patients with unrelated medical conditions.
      All AE- and CE-sera were also examined by the echinococcosis Western blot.
      RESULTS: More sera from patients with AE than with CE showed cross-reactivity in
      the form of ladder-like patterns ("Mikado aspect") and untypical bands at 6-8 kDa
      (71% and 77.4% versus 27.3% and 45.5%, respectively). In contrast, triplets of
      bands in the area above 50 kDa and between 24 and 39-42 kDa were more frequent in
      CE than in AE sera. The fuzzy band at 50-55 kDa typical for cysticercosis was
      absent in all AE and CE sera. CONCLUSIONS: Atypical banding patterns in the
      cysticercosis Western blot should raise the suspicion of a meta?cestode infection
      different from Taenia solium, i.e. Echinococcus multilocularis or E. granulosus,
      especially when the Mikado aspect and an altered 6-8 kDa band is visible in the
      absence of a fuzzy 50-55 kDa band.

PMID- 19748854
TI  - Detection of promoter hypermethylation of the CpG island of E-cadherin in gastric
      cardiac adenocarcinoma.
AB  - AIM: Abnormal hypermethylation of CpG islands associated with tumor suppressor
      genes can lead to transcriptional silencing in neoplasia. The aim of this study
      was to investigate the promoter methylation and expression of E-cadherin gene in
      gastric cardiac adenocarcinoma (GCA). METHODS: A nested MSP approach,
      immunohistochemistry method and RT-PCR were used respectively to examine the
      methylation status of the 5' CpG island of E-cadherin, its protein expression and
      mRNA expression in tumors and corresponding normal tissues. RESULTS: E-cadherin
      was methylated in 63 of 92 (68.5%) tumor specimens, which was significantly
      higher than that in corresponding normal tissues (P<0.001). Methylation
      frequencies of stage III and IV tumor tissues was significantly higher than that
      in stage I and II tumor tissues (P = 0.01). Methylation status of poor
      differentiation group was significantly higher than moderate and poor-moderate
      differentiation groups (P<0.01). By immunostaining 51 of 92 tumor tissues
      demonstrated heterogeneous, positive immunostaining of tumor tissues (44.6%),
      significantly different from matched normal tissues (P<0.001). Positive
      immunostaining of stage III and IV tumor tissues was significantly lower than
      stage I and II tumor tissues (P<0.01). Poor differentiation group was also
      significantly lower than moderate and poor-moderate differentiation groups
      (P<0.05). 80 percent of tumor tissues with E-cadherin gene methylated showed
      inactivated mRNA expression. CONCLUSIONS: High methylation status of the 5' CpG
      island of E-cadherin gene may be one of the mechanisms in the development of
      gastric cardiac adenocarcinoma.

PMID- 19748855
TI  - The use of chicken legs for teaching wound closure skills.
AB  - OBJECTIVE: Training models are required to impart surgical skills, like wound
      closure techniques, prior to practice in patients. In an ideal case, the tissue
      characteristics of the model are close to those of humans, easy to create and of
      low cost. METHODS: Here, we describe a model to train students in wound closure
      technique using conventional chicken legs obtained from the supermarket. RESULTS:
      The described model has good tissue characteristics, does not require any lavish
      preparation and is of minimal cost (0.62 Euro or 0.78 USD). CONCLUSIONS: Chicken
      legs appear to be an appropriate tool for teaching wound closure techniques.

PMID- 19748856
TI  - Evaluation of quantitative liver function tests in HIV-positive patients under
      anti-retroviral therapy.
AB  - BACKGROUND AND AIMS: Quantitative tests of liver function (QTLF) which are based
      on the hepatic metabolism or clearance of test substances have been successfully
      used to predict prognosis of a variety of different liver diseases. Still
      sufficient data in HIV-patients under anti-retroviral therapy (ART) are lacking.
      Therefore, the aim of this prospective study was to investigate if and to what
      extent ART influences a broad panel of quantitative tests of liver function in
      patients with HIV-infection. PATIENTS AND METHODS: Nineteen patients (14 males, 5
      females, mean age 40 years) with HIV-infection underwent QTLF including lidocaine
      half-life test (LHT), galactose elimination capacity (GEC), and indocyanine green
      clearance (IGC). These tests were performed before and 3 to 6 months after
      initiation of anti-retroviral therapy. Twenty age-matched healthy, medication-
      and virus-free adults served as controls. RESULTS: Lidocaine half-life was
      significantly lower in HIV-patients without ART. Combining anti-retroviral
      therapies shifted cytochrome p450 activity back into standard ranges. Galactose
      elimination capacity as a parameter of cytosolic liver function and indocyanine
      green clearance as a parameter of liver perfusion were not affected by ART.
      CONCLUSIONS: QTLF may be a tool to predict prognosis or hepatic complications in
      HIV-infected patients with liver disease. Early determination of lidocaine half
      life seems to be useful - this should be considered during the treatment of HIV
      positive individuals.

PMID- 19748857
TI  - Idiopathic recurrent calcium urolithiasis (IRCU): variation of fasting urinary
      protein is a window to pathophysiology or simple consequence of renal stones in
      situ? A tripartite study in male patients providing insight into oxidative
      metabolism as possible driving force towards alteration of urine composition,
      calcium salt crystallization and stone formation.
AB  - BACKGROUND: In IRCU it is uncertain whether variation of urinary protein,
      especially non-albumin protein (N-Alb-P), is due to the presence of stones or
      reflects alteration of oxidative metabolism. AIMS: To validate in a tripartite
      cross-sectional study of 187 ambulatory male patients, undergoing a standardized
      laboratory programme, whether stones impact on N-Alb-P or the state of oxidative
      metabolism interferes with IRCU pathophysiology. METHODS: In part 1 the strata
      low and high of fasting urinary excretion rate per 2 h of N-Alb-P,
      malonedialdehyde, hypoxanthine, xanthine, pH and other urine components were
      compared, and association with renal stones in situ evaluated; in part 2 the co
      variation of oxidatively modulated environment, fasting urinary pH, calcium (Ca)
      salt crystallization risk and the number of patients with stones in situ was
      examined; in part 3, the nucleation of Ca oxalate and Ca phosphate was tested in
      undiluted postprandial urine of patients and related to the state of oxidative
      metabolism. RESULTS: In part 1, N-Alb-P excretion >4.3 mg was associated with
      increase of blood pressure, excretion of total protein, hypoxanthine (a marker of
      tissue hypoxia), malonedialdehyde (a marker of lipid peroxidation), sodium,
      magnesium, citrate, uric acid, volume, pH, and increase of renal fractional
      excretion of both N-Alb-P and uric acid; when stones were present, urinary pH was
      elevated but other parameters were unaffected. Significant predictors of N-Alb-P
      excretion were malonedialdehyde, fractional N-Alb-P and hypoxanthine. In part 2,
      urine pH >6.14 was associated with unchanged blood pressure and plasma
      vasopressin, increase of blood pH, urinary volume, malonedialdehyde, fractional
      excretion of N-Alb-P, uric acid, Ca phosphate, but not Ca oxalate,
      supersaturation; this spectrum was accompanied by decrease of concentration of
      urinary total and free magnesium, total and complexed citrate, plasma uric acid
      (in humans the major circulating antioxidant) and insulin; the number of stone
      bearing patients was increased. Significant predictors of urine pH were body mass
      index, plasma insulin and uric acid (negative), and urinary xanthine (positive).
      In part 3 low plasma uric acid, not high urinary malonedialdehyde or high ratio
      malonedialdehyde/uric acid was significantly associated with diminished Ca but
      not oxalate tolerance, with the first nucleating crystal type being mostly Ca
      phosphate (hydroxyapatite), in the rest Ca oxalate dihydrate; uricemia correlated
      marginally positively (p = 0.055) with Ca tolerance of urine, stronger with blood
      pressure and insulin, and negatively with urinary xanthine, fractional N-Alb-P,
      volume, sodium. CONCLUSIONS: In IRCU 1) not renal stones in situ, but disturbed
      oxidative metabolism apparently modulates nephron functionality, ending up in
      higher renal N-Alb-P release, urinary volume, sodium and pH of fasting urine; 2)
      etiologically unknown decline of uricemia may represent antioxidant deficiency
      and cause a risk of hydroxyapatite crystallization and stone formation in a
      weakly acidic or alkaline inhibitor-deficient and N-Alb-P-rich milieu; 3) several
      observations, linking oxidative and systemic metabolism, are compatible with Ca
      stone initiation beyond tubules.

PMID- 19748858
TI  - Effects of exercise training on mobilization and functional activity of blood
      derived progenitor cells in patients with acute myocardial infarction.
AB  - BACKGROUND: The aim of the present study was to determine whether regular
      exercise training (ET) is effective at promoting the mobilization of CPCs and
      improving their functional activity in patients with recently acquired myocardial
      infarction (STEMI). Regular physical training has been shown to improve
      myocardial perfusion and cardiovascular function. This may be related in part to
      a mobilization of bone marrow-derived circulating progenitor cells (CPCs) as well
      as an enhanced vascularisation. METHODS: 37 patients with STEMI were randomly
      assigned to an ET group or a non-ET group (controls). Two weeks after STEMI,
      three weeks after regular ET and three months after ET, BNP levels, exercise
      echocardiography and exercise spiroergometry were evaluated. The number of
      CD34+/CD45+ and CD133+/CD45+ CPCs was measured by flow cytometry analysis. The
      migration capacity of the CPCs was determined with a boyden chamber and the
      clonogenic capacity by CFU-assay. RESULTS: In the ET-group the number and
      migration capacity of CPCs increased significantly after regular exercise
      training. The BNP level decreased significantly from 121 +/- 94 to 75 +/- 47
      pg/ml (p<0.001) after the ET period, the left ventricular ejection fraction
      raised in parallel at peak exercise, and the cardiorespiratory condition improved
      as demonstrated by an increase of VO2max (from 1641 +/- 522 to 1842 +/- 724
      ml/min, p<0.02). These three effects persist till three months after the ET
      period. CONCLUSIONS: Regular physical activity appears to predispose the
      mobilization and enhanced functional activity of CPCs, a phenomenon which might
      lead to an improved cardiac function in patients with recently acquired acute
      myocardial infarction.

PMID- 19748859
TI  - Echinacea/sage or chlorhexidine/lidocaine for treating acute sore throats: a
      randomized double-blind trial.
AB  - BACKGROUND: The aim of this trial was to assess the relative efficacy of a
      sage/echinacea spray and a chlorhexidine/lidocaine spray in the treatment of
      acute sore throats. METHODS: This was a multicenter, randomized, double-blind,
      double-dummy controlled trial carried out in eleven general practices in
      Switzerland. A total of 154 patients (133 analyzed in per protocol collective) at
      least 12 years old with acute sore throat present for not more than 72 hours
      prior to inclusion and with a throat score >/=6 participated in the study. They
      used either an echinacea/sage spray or a chlorhexidine/ lidocaine spray with two
      puffs every 2 hours, in a double-dummy blinded manner, up to 10 times daily until
      they were symptom-free, for a maximum of 5 days. The main outcome measures was
      the comparison of response rates during the first three days. A response was
      defined as a decrease of at least 50% of the total symptoms compared to baseline.
      RESULTS: The echinacea/sage treatment exhibited similar efficacy to the
      chlorhexidine/lidocaine treatment in reducing sore throat symptoms during the
      first 3 days (P(x<Y) = .5083). Response rates after 3 days were 63.8% in the
      echinacea/sage group and 57.8% in the chlorhexidine/lidocaine group. For all
      secondary parameters, such as time to becoming symptom free, throat pain, and
      global assessments of efficacy by the physician and patient, no difference
      between the two treatments was seen. They were both very well tolerated.
      CONCLUSION: An echinacea/sage preparation is as efficacious and well tolerated as
      a chlorhexidine/lidocaine spray in the treatment of acute sore throats.

PMID- 19748860
TI  - Gasperini syndrome as clinical manifestation of pontine demyelination.
AB  - The Gasperini syndrome is a very rare brainstem disease characterized by the
      typical combination of ipsilateral lesions of the cranial nerves V-VII and
      dissociated contralateral hemihypesthesia, whereas both contralateral and
      ipsilateral hypacusis was described. Since the first description in 1912, only a
      few cases of this crossed brainstem syndrome were published so far. Pontine
      infarction and bleedings were the reported causes of the syndrome. Here we report
      a 44-year-old man with the classical Gasperini syndrome due to pontine
      demyelination in multiple sclerosis. The clinical findings were correlated with
      changes on MRI. The present case shows that classical crossed brainstem syndromes
      are topological terms not invariably associated with brainstem ischemia in
      particular vascular areas and may contribute to the differential diagnosis of
      peripheral facial nerve palsy.

PMID- 19748861
TI  - Health literacy: a barrier to pharmacist-patient communication and medication
      adherence.
AB  - OBJECTIVE: To present a summary of the existing literature on medication
      nonadherence, health literacy, and use of written patient information in health
      care and pharmacy in particular. DATA SOURCES: Searches of Medline, PubMed, and
      International Pharmaceutical Abstracts databases were conducted using one or more
      of the following terms: adherence/nonadherence, compliance/noncompliance,
      printed/written information, literacy, patient education, communication, and
      health literacy. These terms were combined with the following search terms: drug
      information, readability, medication/drug, patient, pharmacy/pharmacist, and
      prescription. References of pertinent articles were hand searched to retrieve
      additional articles. DATA EXTRACTION: By the author. DATA SYNTHESIS: Articles
      were grouped and summarized into three broad categories (nonadherence, health
      literacy, and communicating health information to patients), with an emphasis on
      the use of written patient information in health care and pharmacy practice in
      particular. The complexities inherent in nonadherence behavior, health literacy,
      and patient education are summarized, and suggestions for enhancing medication
      adherence, especially for patients with low health literacy skills, are provided.
      CONCLUSION: The health literacy skills of American adults have not changed
      considerably during the previous decade. This makes use of written patient
      medication information in pharmacy practice problematic for some patients.
      Limited health literacy has been associated with poorer health, medication
      nonadherence, medication errors, higher medical expenses, and increased
      hospitalization. A need exists for identifying patients with limited health
      literacy and tailoring medication counseling to their needs.

PMID- 19748863
TI  - Improving medication delivery and counseling in community pharmacy.

PMID- 19748864
TI  - Pharmacist roles in combating prescription drug abuse.

PMID- 19748865
TI  - RxPATROL: a Web-based tool for combating pharmacy theft.
AB  - OBJECTIVE: To report the incidence of pharmacy-related burglaries and robberies
      and characteristics of pharmacies where such crimes have occurred using recent
      data from Rx Pattern Analysis Tracking Robberies & Other Losses (RxPATROL), a
      national Web-based information clearinghouse on pharmacy-related theft of
      prescription medications and over-the-counter products. DESIGN: Descriptive,
      nonexperimental study. SETTING: United States between 2005 and 2006.
      PARTICIPANTS: Not applicable. INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURES: Number of pharmacy theft reports received; incident type, date, and
      location; point of entry; and pharmacy security features. RESULTS: Between 2005
      and 2006, 202 pharmacy burglary and 299 pharmacy robbery reports from 45
      different states were filed with RxPATROL. More than 70% of pharmacies reporting
      such crimes lacked a security camera. Among those reporting a burglary, 60%
      lacked dead bolt locks, a solid exterior door, a motion detector device, or a
      safe or vault for storage of controlled substances. Burglars most often obtained
      access to the pharmacy via the front door. CONCLUSION: RxPATROL is a Web-based
      tool that can assist pharmacies and law enforcement in collaborating more
      effectively to combat and prevent pharmacy-related crimes.

PMID- 19748866
TI  - Survey of dispensing error practices in community pharmacies in Finland: a
      nationwide study.
AB  - OBJECTIVES: To assess the actions taken to manage dispensing errors, to
      investigate pharmacists' perceptions of ideal methods for managing dispensing
      errors, and to evaluate the reliability of in-house dispensing error reporting
      systems. DESIGN: National cross-sectional survey. SETTING: Main outlets of all
      privately owned Finnish community pharmacies (n = 599) in March 2005.
      PARTICIPANTS: Owners and operational managers of Finnish community pharmacies.
      INTERVENTION: Mail survey containing structured and open-ended questions. MAIN
      OUTCOME MEASURES: Current actions taken in the dispensing error managing process,
      pharmacist perceptions on the ideal ways of action to manage dispensing errors,
      and reported dispensing error rates. RESULTS: 340 participants responded to the
      survey (response rate 57%). Almost 90% of the responding outlets documented
      dispensing errors at least occasionally, 47% always documented, and 29% almost
      always documented. Discussion about dispensing errors was considered the most
      ideal method for managing dispensing errors in the pharmacy (76% of the
      respondents), followed by documenting them (45%). The error rate collected from
      in-house error reporting systems was 14 per 100,000 prescriptions dispensed in
      2004. CONCLUSION: Most Finnish community pharmacies have an in-house dispensing
      error reporting system, but reporting has not been fully implemented in all
      pharmacies. The actual error reporting in most Finnish community pharmacies is
      not reliable and needs further development and coordination. Discussing
      dispensing errors and documenting dispensing errors were reported as the most
      ideal methods for managing errors. Respondents indicated a hope that dispensing
      errors would be discussed more frequently with the whole staff. These findings
      demonstrate that Finnish community pharmacists are aware of some of the
      principles of managing dispensing errors based on the system approach and the
      benefits of error reporting systems in managing dispensing errors.

PMID- 19748867
TI  - Generating demand for pharmacist-provided medication therapy management:
      identifying patient-preferred marketing strategies.
AB  - OBJECTIVE: To identify effective strategies for marketing pharmacist-provided
      medication therapy management (MTM) services to patients in a self-insured
      employer setting. DESIGN: Qualitative study. SETTING: University of Pittsburgh
      during March through May 2008. PARTICIPANTS: 26 university employees taking at
      least one chronic medication. INTERVENTION: Three focus group sessions were
      conducted using a semistructured topic guide to facilitate the discussion. MAIN
      OUTCOME MEASURES: Employees' perceived medication-related needs, perceived
      benefits of pharmacist-provided MTM, potential barriers for employee
      participation in MTM, and effective strategies for marketing MTM. RESULTS:
      Participants reported concerns with timing of doses, medication costs, access,
      and ensuring adherence. Participants generally felt positively toward
      pharmacists; however, the level of reported patient contact with pharmacists
      varied among participants. Some participants questioned pharmacists' education
      and qualifications for this enhanced role in patient care. Perceived benefits of
      MTM noted by participants included the opportunity to obtain personalized
      information about their medications and the potential for improved communication
      among their health providers. Barriers to patient participation were out-of
      pocket costs and lack of time for MTM visits. Participants suggested use of
      alternative words to describe MTM and marketing approaches that involve personal
      contact. CONCLUSION: Pharmacists should emphasize parts of MTM that patients feel
      are most beneficial (i.e., provision of a personal medication record) and use
      patient-friendly language to describe MTM when marketing their practice. Patients
      will need greater exposure to the concept of MTM and the pharmacists' role in
      order to correctly describe and assign value to this type of pharmacist patient
      care practice.

PMID- 19748868
TI  - Comparison of the claim percent gross margin earned by Texas community
      independent pharmacies for dual-eligible beneficiary claims before and after
      Medicare Part D.
AB  - OBJECTIVES: To describe dual eligibles' claims before and after Medicare Part D
      and to evaluate the effect that Medicare Part D has had on the claim percent
      gross margin (CPGM) earned by Texas community independent pharmacies. DESIGN:
      Nonexperimental time series study. SETTING: Texas, October 2005 through September
      2006. PARTICIPANTS: 313 community independent pharmacies. INTERVENTION: Review of
      more than 150,000 Medicaid and 300,000 Medicare Part D claims acquired from a
      drug claims processor. MAIN OUTCOME MEASURES: CPGM per prescription claim before
      and after the implementation of Medicare Part D, controlling for generic/brand
      drug status. RESULTS: The mean CPGM for prescriptions dispensed before Part D
      (Medicaid claims) was 26.7%. The mean CPGM for claims dispensed after Part D
      (Medicare claims) was 17.0% (using ingredient costs in 2006 dollars) or 20.4%
      (using ingredient costs adjusted to 2005 dollars), a reduction of 36.3% and
      23.6%, respectively. Under both Medicaid and Part D, pharmacies earned higher
      margins for generic drugs (39.9% and 29.5%, respectively) than for brand-name
      drugs (8.7% and 8.3%, respectively). CONCLUSION: These results support community
      pharmacy assertions of lower reimbursements from Part D payers compared with
      Medicaid payers. Based on these results, pharmacies can respond to this evolving
      environment by carefully reviewing their Part D plans' impact on CPGM and taking
      available steps to increase the proportion of generic drugs dispensed to Medicare
      beneficiaries.

PMID- 19748869
TI  - Outcomes of medication therapy review in a family medicine clinic.
AB  - OBJECTIVE: To evaluate the effects of pharmacist-conducted medication therapy
      review (MTR) and intervention on the quality of care of patients in a family
      medicine clinic. DESIGN: Prospective, observational, cohort study. SETTING:
      Family medicine clinic in Minnesota during 2000-2001. PATIENTS: Patients were
      enrolled in a statewide nonprofit managed care organization; selected patients
      were seen by a clinical pharmacist. INTERVENTION: Following MTR, medication
      related problems (MRPs) were identified and resolved. MAIN OUTCOME MEASURES: MRPs
      identified and resolved, improvement in clinical status, achievement of
      therapeutic goals, important medication use, and reduction in number of
      medications. RESULTS: 92 patients were included in the study, with a total of 203
      patient encounters. MRPs were identified in 90% of patients, with a total of 250
      identified. Overall status of medical conditions improved in 45% of patients, 46%
      stayed the same, and 9% declined (P < 0.001). Significant improvement in status
      was found for hypertension (P = 0.007), dyslipidemia (P = 0.002), and asthma (P =
      0.011). Significant improvement was seen for aspirin use for myocardial
      infarction prevention (50% vs. 93%, P = 0.031) and inhaled steroids for asthma
      (36% vs. 64%, P = 0.031). The number of medications was reduced from an average
      of 3.92 to 3.04 (P < 0.001) per patient. CONCLUSION: MTR and intervention by a
      pharmacist positively affected quality of care in this family medicine clinic.

PMID- 19748870
TI  - Daily versus single-day offering of influenza vaccine in community pharmacies.
AB  - OBJECTIVE: To assess the cumulative number of influenza vaccinations delivered
      per pharmacy in relation to number of days of offering vaccination per season.
      METHODS: Automated records of pharmacies involved in a cohort study were queried
      for number of influenza vaccinations delivered in each of three influenza
      vaccination seasons between 1996 and 1998. Eleven pharmacies in Washington State
      were compared with 13 pharmacies in Oregon, contrasting years when nurses offered
      influenza vaccine 1 day per season with years when pharmacists offered influenza
      vaccine daily for several months. RESULTS: Pharmacies in which pharmacists
      offered influenza vaccination daily averaged 528 to 807 doses per pharmacy per
      season compared with 91 to 233 doses per pharmacy in seasons when nurses offered
      vaccination on a single day. CONCLUSION: Professionals dedicated to providing
      adult vaccination on any given day outperformed professionals who attended to
      both vaccination and other clinical duties, but the cumulative effect of offering
      vaccinations on multiple days can achieve a greater number of vaccinations over a
      several-month interval.

PMID- 19748871
TI  - Latino patients' preferences for medication information and pharmacy services.
AB  - OBJECTIVES: To examine (1) Latino patients' language preferences for receiving
      verbal and written medication information in community pharmacies, (2) the types
      of problems and concerns Latino patients report about using their medications,
      and (3) the factors that Latino patients believe are important when choosing a
      community pharmacy. METHODS: Individuals were eligible to participate if they
      were 18 years of age or older, if they self-identified as being Latino, and if
      they or their children were currently taking prescription medications. All 93
      participating individuals were interviewed in Spanish. RESULTS: The majority of
      patients did not always receive their prescription labels or written medication
      information in Spanish. Approximately 52% of the respondents preferred to receive
      verbal information in Spanish without an interpreter, and 21.5% preferred to
      receive it in Spanish with an interpreter. Most respondents (70%) preferred
      written information in Spanish, and 21.5% preferred written information in both
      Spanish and English. The most commonly reported problems were difficulty paying
      for medications, difficulty reading the English on the prescription labels, and
      adverse effects. Participants valued pharmacies with friendly and respectful
      employees. CONCLUSION: Study participants reported many problems or concerns in
      using their medications, and the majority preferred receiving written and verbal
      information about their medication in Spanish. Pharmacies need to find better
      ways of providing services to the rapidly growing Latino population.

PMID- 19748872
TI  - Afghanistan: an assessment of the status of health care and pharmacy mentoring
      efforts in an Afghan National Army hospital.
AB  - BACKGROUND: The United States and Coalition countries initiated mentoring in
      Afghanistan as a means of training the Afghan people for independence, to include
      democratic self-governance and national defense. Several medical Embedded
      Training Teams are executing the medical component of the mentoring mission at
      Afghan Army hospitals around the country. OBJECTIVES: To provide a brief synopsis
      of Afghanistan history, review the status of Afghanistan health care, and provide
      an overview of pharmacy mentoring efforts by an Air Force pharmacist and pharmacy
      technician at Kandahar Regional Military Hospital. SUMMARY: Afghanistan health
      care has suffered from neglect, and improving health care in the country is an
      important part of bolstering their military and the country as a whole.
      Afghanistan is rebounding from decades of civil war and occupation from a number
      of oppressive regimes, and the Afghan military faces considerable challenges.
      Challenges specific to military pharmacy include lack of established policies and
      procedures, medication shortages, medication quality issues, and lack of basic
      equipment, supplies, and training. CONCLUSION: Through ingenuity and
      determination, Afghan and Coalition pharmacists are working together to make
      progress in advancing the practice of pharmacy in Afghanistan.

PMID- 19748873
TI  - Forging a novel provider and payer partnership in Wisconsin to compensate
      pharmacists for quality-driven pharmacy and medication therapy management
      services.
AB  - OBJECTIVE: To describe the Wisconsin Pharmacy Quality Collaborative (WPQC), a
      quality-based network of pharmacies and payers with the common goals of improving
      medication use and safety, reducing health care costs for payers and patients,
      and increasing professional recognition and compensation for pharmacist-provided
      services. SETTING: Wisconsin between 2006 and 2009. PRACTICE DESCRIPTION:
      Community (independent, chain, and health-system) pharmacies and private and
      public health care payers/purchasers with support from the McKesson Corporation.
      PRACTICE INNOVATION: This initiative aligns incentives for pharmacies and payers
      through implementation of 12 quality-based pharmacy requirements as conditions of
      pharmacy participation in a practice-advancement pilot. Payers compensate network
      pharmacies that meet the quality-based requirements for two levels of pharmacy
      professional services (level 1, intervention-based services; level 2,
      comprehensive medication review and assessment services). MAIN OUTCOME MEASURES:
      The pilot project is designed to measure the following outcomes: medication-use
      quality improvements, frequency and types of services provided, drug therapy
      problems, patient safety, cost savings, identification of factors that facilitate
      pharmacist participation, and patient satisfaction. RESULTS: The Pharmacy Society
      of Wisconsin created the WPQC network, which consists of 53 pharmacies, 106
      trained pharmacists, 45 student pharmacists, 6 pharmacy technicians, and 2
      initial payers. A quality assurance process is followed approximately quarterly
      to audit the 12 network quality requirements. An evaluation of this collaboration
      is being conducted. CONCLUSION: This program demonstrates that collaboration
      among payers and pharmacists is possible and can result in the development of an
      incentive-aligned program that stresses quality patient care, standardized
      services, and professional service compensation for pharmacists. This combination
      of a quality-based credentialing process with a professional services
      reimbursement schedule is unique and has the promise to enhance the ambulatory
      pharmacy practice model.

PMID- 19748874
TI  - Telepharmacy services in an urban community health clinic system.
AB  - OBJECTIVE: To describe telepharmacy-related services and outcome. SETTING:
      Suburban western Washington State during 2007 to 2008. PRACTICE DESCRIPTION: Five
      network clinics without in-house pharmacies are remotely connected to a central
      pharmacy to provide telepharmacy services. PRACTICE INNOVATION: Automated drug
      dispensing system (ADDS) units, webcams, and electronic medical charts were used
      to provide remote medication order processing/dispensing, patient counseling,
      refill authorizations, and medication assistance referral services. MAIN OUTCOME
      MEASURES: Patient demographics; numbers of dispensed medications, patient
      consultations, refill authorizations, and service referrals; pharmacist feedback;
      and workflow changes. RESULTS: At five network sites, 12,000 patients received
      3,282 new prescriptions per month with webcam-enabled consultations, 589 monthly
      refill prescriptions, 2,800 pharmacist-provided refill authorizations, and 250
      medication assistance referrals. Antibiotics were the most frequently dispensed
      medications. Pharmacists commented that webcam-enabled interviews provided better
      privacy and longer counseling duration. Six new staff members (one pharmacist and
      five pharmacy technicians) were added. Workspace and staff responsibilities were
      reassigned to facilitate medication prepackaging and ADDS prescription
      processing. CONCLUSION: Expanded application of telepharmacy technology can
      improve patient access to pharmaceutical care beyond remote medication dispensing
      to include point-of-care refill authorization and medication assistance
      referrals. Further research to explore patient-focused services and to assess
      economic, humanistic, and clinical outcomes of telepharmacy services is needed.

PMID- 19748875
TI  - Implementation of a comprehensive pretravel health program in a supermarket chain
      pharmacy.
AB  - OBJECTIVE: To describe the procedures for implementing a comprehensive pretravel
      health program in a supermarket chain pharmacy. SETTING: Central Virginia
      (Richmond, Fredericksburg, Williamsburg, and Roanoke) between 2000 and 2008.
      PRACTICE DESCRIPTION: Ukrop's is a local supermarket chain with 29 stores, 20 of
      which have pharmacies. Ukrop's Pharmacy offers enhanced patient care services,
      including medication therapy management, wellness services, diabetes education
      and management, smoking cessation, and immunizations. PRACTICE INNOVATION:
      Comprehensive pretravel health program. MAIN OUTCOME MEASURES: Number of patients
      participating in the pretravel health program and number of vaccinations
      administered by pharmacists. RESULTS: An average of 1,000 patients per year
      participate in the pretravel health program, and approximately 1,900 vaccines are
      administered each year. CONCLUSION: A comprehensive pretravel program is a
      successful service in a supermarket chain pharmacy. It provides another option
      for travelers seeking pretravel health care.

PMID- 19748876
TI  - Unique role of consumer studies in nonprescription drug development.
AB  - OBJECTIVE: To inform the health care community about nonprescription drug
      labeling and consumer studies unique and integral to the nonprescription drug
      development process. SETTING: Data from consumer studies are essential for many
      nonprescription drug approvals. These studies are conducted to help predict
      actual consumer behavior in the marketplace if the product is approved. They test
      whether potential consumers understand a label (label comprehension study), can
      properly decide if a product is appropriate for them to use (self-selection
      study), and can use a product in accordance with the label (actual use study).
      The design and interpretation of these studies often pose unique challenges.
      CONCLUSION: Consumer studies are often part of a nonprescription drug development
      program. Continued efforts to improve consumer research should result in greater
      access to safe and effective nonprescription drug products for the American
      public.

PMID- 19748878
TI  - Patrick Henry Costello 1897-1971: architect of reciprocal standards.

PMID- 19748879
TI  - Doubled immunization efforts for pandemic and seasonal influenza.

PMID- 19748880
TI  - New drugs: tapentadol hydrochloride, tolvaptan, and benzyl alcohol.

PMID- 19748881
TI  - Pharmacy services in ICU, antidepressant treatment, and Swedish pharmacists.

PMID- 19748882
TI  - A cross-sectional study on levels of secondhand smoke in restaurants and bars in
      five cities in China.
AB  - OBJECTIVES: To assess indoor secondhand smoke (SHS) exposure in restaurants and
      bars via PM(2.5) level measurements in five cities in China. METHODS: The study
      was conducted from July to September in 2007 in Beijing, Xi'an, Wuhan, Kunming
      and Guiyang. PM(2.5) concentrations were measured in 404 restaurants and bars
      using portable aerosol monitors. The occupant density and the active smoker
      density were calculated for each venue sampled. RESULTS: Among the 404 surveyed
      venues, 23 had complete smoking bans, nine had partial smoking bans and 313
      (77.5%) had smoking observed during sampling. The geometric mean of indoor
      PM(2.5) levels in venues with smoking observed was 208 MUg/m(3) and 99 MUg/m(3)
      in venues without smoking observed. When outdoor PM(2.5) levels were adjusted,
      indoor PM(2.5) levels in venues with smoking observed were consistently
      significantly higher than those in venues without smoking observed (F=80.49,
      p<0.001). Indoor PM(2.5) levels were positively correlated with outdoor PM(2.5)
      levels (partial rho=0.37 p<0.001) and active smoker density (partial rho=0.34,
      p<0.001). CONCLUSIONS: Consistent with findings in other countries, PM(2.5)
      levels in smoking places are significantly higher than those in smoke-free places
      and are strongly related to the number and density of active smokers. These
      findings document the high levels of SHS in hospitality venues in China and point
      to the urgent need for comprehensive smoke-free laws in China to protect the
      public from SHS hazards, as called for in Article 8 of the Framework Convention
      on Tobacco Control, which was ratified by China in 2005.

PMID- 19748883
TI  - Adverse effects of a social contract smoking prevention program among children in
      Quebec, Canada.
AB  - OBJECTIVE: To evaluate the impact of a smoke-free class competition in elementary
      schools in Quebec, Canada before widespread dissemination of the program across
      the province. METHODS: In a quasiexperimental study design, 843 students in 27
      schools exposed to "Mission TNT.06" were compared to 1213 students in 57 matched
      comparison schools. Baseline data were collected in grade 6 prior to
      implementation of the program. Follow-up data were collected in grade 7 after
      students had transitioned to secondary school. RESULTS: The program improved
      knowledge about the harmful effects of second-hand smoke, but had no impact on
      knowledge about the harmful effects of smoking, attitudes about the acceptability
      of cigarettes, beliefs about the tobacco industry, or self-efficacy to resist
      peer pressure to smoke. After exposure to the program, intervention students were
      more likely to misreport their smoking status and to report unfavourable
      attitudes about classmates who smoke. CONCLUSION: Mission TNT.06 may encourage
      young smokers to misreport their smoking status and to marginalise classmates who
      smoke. These findings prompted recommendations to conduct more in-depth
      evaluation of the smoke-free class competition before widespread dissemination of
      the program across the province.

PMID- 19748884
TI  - Regulating the tobacco retail environment: beyond reducing sales to minors.
AB  - The World Health Organization Framework Convention on Tobacco Control (FCTC) has
      little to say about the regulation of tobacco retailing, with most research and
      policy debate having been restricted to confining sales to adults and removing
      advertising displays, including packs. Tobacco retailing is largely unregulated,
      reflecting the historical regulatory trivialisation of tobacco products, now
      demonstrably anachronistic with the advent of near global support for the FCTC.
      This situation contrasts markedly with the regulation of pharmaceuticals, and
      many other goods and services subject to a wide variety of restrictions. This
      review proposes that the international tobacco control community should open up
      debate on retail regulation to examine the suitability of principles long
      accepted in pharmaceutical regulation. These include: restrictions on the number
      and location of tobacco retail outlets, the banning of tobacco retail displays,
      floor (minimum) price controls, restricting the amount of tobacco smokers could
      purchase over a given time and loss of retail licensure following breaches of any
      of the conditions of license. It proposes that retail licenses should be heavily
      restricted and tradable, becoming valuable commercial assets, where the threat of
      loss or revocation would act as an incentive for strict adherence to the measures
      proposed.

PMID- 19748885
TI  - Smoke-free homes in England: prevalence, trends and validation by cotinine in
      children.
AB  - OBJECTIVE: To examine the prevalence of smoke-free homes in England between 1996
      and 2007 and their impact on children's exposure to second-hand smoke via a
      series of annual cross-sectional surveys: the Health Survey for England. These
      comprised nationally representative samples of non-smoking children aged 4-15 (n
      = 13 365) and their parents interviewed in the home. Main outcome measures were
      cotinine measured in saliva, smoke-free homes defined by "no" response to "Does
      anyone smoke inside this house/flat on most days?", self-reported smoking status
      of parents and self-reported and cotinine validated smoking status in children.
      RESULTS: The proportion of homes where one parent was a smoker that were smoke
      free increased from 21% in 1996 to 37% in 2007, and where both parents were
      smokers from 6% to 21%. The overwhelming majority of homes with non-smoking
      parents were smoke free (95% in 1996; 99% in 2007). For children with non-smoking
      parents and living in a smoke-free home the geometric mean cotinine across all
      years was 0.22 ng/ml. For children with one smoking parent geometric mean
      cotinine levels were 0.37 ng/ml when the home was smoke free and 1.67 ng/ml when
      there was smoking in the home; and for those with two smoking parents, 0.71 ng/ml
      and 2.46 ng/ml. There were strong trends across years for declines in cotinine
      concentrations in children in smoke-free homes for the children of smokers and
      non-smokers. CONCLUSIONS: There has been a marked secular trend towards smoke
      free homes, even when parents themselves are smokers. Living in a smoke-free home
      offers children a considerable, but not complete, degree of protection against
      exposure to parental smoking.

PMID- 19748886
TI  - Smoking-attributable deaths and potential years of life lost from a large,
      representative study in China.
AB  - OBJECTIVES: To provide a more accurate estimate of early smoking-attributable
      mortality and potential years of life lost using data from a representative study
      of 103 study areas in China. METHODS: Two datasets were employed as follows.
      Firstly, retrospective national mortality survey data, which included a
      population of 67 million in 103 study areas, and about 1 million adults who died
      in 1986-1988; secondly, nationally representative case-control comparative data
      was extracted from the survey data to measure the effect of smoking on age trends
      in smoking-attributable mortality. Potential years of life lost, and sex
      differences in life expectancy in smokers and non-smokers in the total population
      aged 35 and over were also estimated. RESULTS: Tobacco caused 11.2% (16.0% of men
      and 3.7% of women) of total deaths in 1987, and more than two-thirds of these
      excess deaths occurred between the ages of 50 and 74 years, but only less than 5%
      excess deaths occurred at ages under 50. Although life expectancies varied with
      region or sex differences, the years of life lost attributable to smoking was
      almost the same. Smokers at age 35 lost about 3 years of life expectancy in
      comparison with never smokers. The study also confirmed that more than 50% of the
      sex difference in life expectancy was accounted for by smoking. CONCLUSION: Fully
      understanding the consequences of smoking in relation to mortality can clarify
      its effects on the health and longevity of the entire population.

PMID- 19748887
TI  - Achieving fire-safe cigarette legislation through coalition-based legislative
      advocacy.
AB  - Advocates who work for tobacco control legislation through coalition-based policy
      advocacy have access to a broad base of support and resources that are critical
      to overcoming the tobacco industry lobby. This article provides an example of how
      a coalition-based advocacy strategy that engaged a diverse group of stakeholders
      and was supported by a national coordinating movement achieved state level fire
      safe cigarette legislation in a tobacco-producing and manufacturing state.

PMID- 19748888
TI  - Rescue of a trafficking defective human pacemaker channel via a novel mechanism:
      roles of Src, Fyn, and Yes tyrosine kinases.
AB  - Therapeutic strategies such as using channel blockers and reducing culture
      temperature have been used to rescue some long QT-associated voltage-gated
      potassium Kv trafficking defective mutant channels. A hyperpolarization-activated
      cyclic nucleotide-gated HCN4 pacemaker channel mutant (D553N) has been recently
      found in a patient associated with cardiac arrhythmias including long QT. D553N
      showed the defective trafficking to the cell surface, leading to little ionic
      current expression (loss-of-function). We show in this report that enhanced
      tyrosine phosphorylation mediated by Src, Fyn, and Yes kinases was able to
      restore the surface expression of D553N for normal current expression. Src or
      Yes, but not Fyn, significantly increased the current density and surface
      expression of D553N. Fyn accelerated the activation kinetics of the rescued
      D553N. Co-expression of D553N with Yes exhibited the slowest activation kinetics
      of D553N. Src, Fyn, and Yes significantly enhanced the tyrosine phosphorylation
      of D553N. A combination of Src, Fyn, and Yes rescued the current expression and
      the gating of D553N comparable with those of wild-type HCN4. In conclusion, we
      demonstrate a novel mechanism using three endogenous Src kinases to rescue a
      trafficking defective HCN4 mutant channel (D553N) by enhancing the tyrosine
      phosphorylation of the mutant channel protein.

PMID- 19748889
TI  - Suppression of p38 MAPK and JNK via Akt-mediated inhibition of apoptosis signal
      regulating kinase 1 constitutes a core component of the beta-cell pro-survival
      effects of glucose-dependent insulinotropic polypeptide.
AB  - Glucose-dependent insulinotropic polypeptide (GIP) potentiates glucose-stimulated
      insulin secretion, insulin biosynthesis, and beta-cell proliferation and
      survival. In previous studies GIP was shown to promote beta-cell survival by
      modulating the activity of multiple signaling modules and regulating gene
      transcription of pro- and anti-apoptotic bcl-2 family proteins. We have now
      evaluated the mechanisms by which GIP regulates the dynamic interactions between
      cytoplasmic bcl-2 family members and the mitochondria in INS-1 cells during
      apoptosis induced by treatment with staurosporine (STS), an activator of the
      mitochondria-mediated apoptotic pathway. STS induced translocation of bad and
      bimEL, activation of mitochondrial bax, release of mitochondrial cytochrome c,
      cleavage of caspase-3, and apoptosis. Each response was significantly diminished
      by GIP. Using selective enzyme inhibitors, overexpression of dominant-negative
      Akt, and Akt siRNA, it was demonstrated that GIP promoted beta-cell survival via
      Akt-dependent suppression of p38 MAPK and JNK and that combined inhibition was
      sufficient to explain the entire pro-survival responses to GIP during STS
      treatment. This signaling pathway also explained the pro-survival effects of GIP
      on INS-1 cells exposed to two other promoters of stress: thapsigargin
      (endoplasmic reticulum stress) and etoposide (genotoxic stress). Importantly, we
      discovered that GIP suppressed p38 MAPK and JNK via Akt-mediated changes in the
      phosphorylation state of the apoptosis signal-regulating kinase 1 in INS-1 cells
      and human islets, resulting in inhibition of its activity. Inhibition of
      apoptosis by GIP is therefore mediated via a key pathway involving Akt-dependent
      inhibition of apoptosis signal-regulating kinase 1, which subsequently prevents
      the pro-apoptotic actions of p38 MAPK and JNK.

PMID- 19748890
TI  - Prion-induced activation of cholesterogenic gene expression by Srebp2 in neuronal
      cells.
AB  - Prion diseases are neurodegenerative diseases associated with the accumulation of
      a pathogenic isoform of the host-encoded prion protein. The cellular responses to
      prion infection are not well defined. By performing microarray analysis on
      cultured neuronal cells infected with prion strain 22L, in the group of up
      regulated genes we observed predominantly genes of the cholesterol pathway.
      Increased transcript levels of at least nine enzymes involved in cholesterol
      synthesis, including the gene for the rate-limiting hydroxymethylglutaryl-CoA
      reductase, were detected. Up-regulation of cholesterogenic genes was attributable
      to a prion-dependent increase in the amount and activity of the sterol regulatory
      element-binding protein Srebp2, resulting in elevated levels of total and free
      cellular cholesterol. The up-regulation of cholesterol biosynthesis appeared to
      be a characteristic response of neurons to prion challenge, as cholesterogenic
      transcripts were also elevated in persistently infected GT-1 cells and prion
      exposed primary hippocampal neurons but not in microglial cells and primary
      astrocytes. These results convincingly demonstrate that prion propagation not
      only depends on the availability of cholesterol but that neuronal cells
      themselves respond to prions with specific up-regulation of cholesterol
      biosynthesis.

PMID- 19748891
TI  - Munc18/Syntaxin interaction kinetics control secretory vesicle dynamics.
AB  - In neuronal and hormonal release, regulated exocytosis requires an essential set
      of proteins: the soluble N-ethylmaleimide sensitive-factor attachment receptor
      proteins (SNAREs) syntaxin 1, SNAP-25, VAMP, and their regulator, Munc18.
      Recently, it was found that Munc18-1 can interact with syntaxin 1 through
      distinct mechanisms: an inhibitory mode enveloping syntaxin (mode 1),
      sequestering it from SNARE protein interactions, and direct binding to an
      evolutionarily conserved N-terminal peptide of syntaxin (mode 2/3). The latter
      interaction has been proposed to control "priming" of the fusion reaction,
      defined using electrophysiology, but it is unknown how this interaction is
      regulated, and any dynamic effect at the molecular or vesicular level in cells
      remains undiscovered. We now show that a phosphorylation site in syntaxin 1
      (Ser(14)) regulates the N-terminal interaction with Munc18-1. Probing syntaxin 1
      association with Munc18-1, in real-time and in living cells, we found that
      modification of Ser(14) modulated the dynamics of this interaction, specifically
      at the plasma membrane. Destabilization of this dynamic interaction enhanced
      vesicle immobilization at the plasma membrane with a resulting inhibition of
      exocytosis.

PMID- 19748892
TI  - A sporadic Parkinson disease model via silencing of the ubiquitin-proteasome/E3
      ligase component SKP1A.
AB  - The aim of this study was to develop a new model of sporadic Parkinson disease
      (PD) based on silencing of the SKP1A gene, a component of the ubiquitin
      proteasome/E3 ligase complex, Skp1, Cullin 1, F-box protein, which was found to
      be highly decreased in the substantia nigra of sporadic PD patients. Initially,
      an embryonic mouse substantia nigra-derived cell line (SN4741 cells) was infected
      with short hairpin RNA lentiviruses encoding the murine transcript of the SKP1A
      gene or with scrambled vector. SKP1A silencing resulted in increased
      susceptibility to neuronal damages induced by the parkinsonism-inducing
      neurotoxin 1-methyl-4-phenylpyridinium ion and serum starvation, in parallel with
      a decline in the expression of the dopaminergic markers, dopamine transporter and
      vesicular monoamine transporter-2. SKP1A-deficient cells presented a delay in
      completion of the cell cycle and the inability to arrest at the G(0)/G(1) phase
      when induced to differentiate. Instead, the cells progressed through S phase,
      developing rounded aggregates with characteristics of aggresomes including
      immunoreactivity for gamma-tubulin, alpha-synuclein, ubiquitin, tyrosine
      hydroxylase, Hsc-70 (70-kDa heat shock cognate protein), and proteasome subunit,
      and culminating in a lethal phenotype. Conversely, stably enforced expression of
      wild type SKP1A duplicated the survival index of naive SN4741 cells under
      proteasomal inhibition injury, suggesting a new structural role of SKP1 in
      dopaminergic neuronal function, besides its E3 ligase activity. These results
      link, for the first time, SKP1 to dopamine neuronal function and survival,
      suggesting an essential role in sporadic PD. In summary, this new model has
      reproduced to a significant extent the molecular alterations described in
      sporadic PD at the cellular level, implicating Skp1 as a potential modifier in
      sporadic PD neurodegeneration.

PMID- 19748893
TI  - Diacylglycerol enrichment of endoplasmic reticulum or lipid droplets recruits
      perilipin 3/TIP47 during lipid storage and mobilization.
AB  - Fatty acid-induced triacylglycerol synthesis produces triacylglycerol droplets
      with a protein coat that includes perilipin 3/TIP47 and perilipin 4/S3-12. This
      study addresses the following two questions. Where do lipid droplets emerge, and
      how are their coat proteins recruited? We show that perilipin 3- and perilipin 4
      coated lipid droplets emerge along the endoplasmic reticulum (ER). Blocking
      membrane trafficking with AlF(4)(-) during fatty acid-induced triacylglycerol
      synthesis drove perilipin 3 to the tubular ER. Forskolin, which like AlF(4)(-)
      activates adenylate cyclase, did not redistribute perilipin 3, but when added
      together with AlF(4)(-) perilipin 3 was recruited to lipid droplets rather than
      the ER. Thus inhibiting trafficking with AlF(4)(-) redistributed perilipin 3
      differently under conditions of triacylglycerol synthesis (fatty acid addition)
      versus hydrolysis (forskolin) suggesting a shared acylglycerol-mediated
      mechanism. We tested whether diacylglycerol (DG), the immediate precursor of
      triacylglycerol and its first hydrolytic product, affects the distribution of
      perilipin 3. Stabilizing DG with the DG lipase inhibitor RHC80267 enhanced the
      perilipin 3 recruited to lipid droplets and raised DG levels in this fraction.
      Treating cells with a membrane-permeable DG recruited perilipin 3 to the ER.
      Stabilizing DG, by blocking its hydrolysis with RHC80267 or its acylation with
      triacsin C, enhanced recruitment of perilipin 3 to the ER. Expressing the ER
      enzyme DGAT1, which removes DG by converting it to triacylglycerol, attenuated
      perilipin 3 DG-induced ER recruitment. Membrane-permeable DG also drove perilipin
      4 and 5 onto the ER. Together the data suggest that these lipid droplet proteins
      are recruited to DG-enriched membranes thereby linking lipid coat proteins to the
      metabolic state of the cell.

PMID- 19748894
TI  - MKP-1 is necessary for T cell activation and function.
AB  - MAPKs are evolutionarily conserved immune regulators. MAPK phosphatases (MKPs)
      that negatively regulate MAPK activities have recently emerged as critical
      players in both innate and adaptive immune responses. MKP-1, also known as DUSP1,
      was previously shown to negatively regulate innate immunity by inhibiting pro
      inflammatory cytokine production. Here, we found that MKP-1 is necessary in T
      cell activation and function. MKP-1 deficiency in T cells impaired the
      activation, proliferation, and function of T cells in vitro, associated with
      enhanced activation of JNK and reduced NFATc1 translocation into the nucleus.
      Consistently, MKP-1(-/-) mice were defective in anti-influenza immunity in vivo
      and resistant to experimental autoimmune encephalomyelitis. Our results thus
      demonstrate that MKP-1 is a critical positive regulator of T cell activation and
      function and may be targeted in treatment of autoimmune diseases.

PMID- 19748895
TI  - Crowded cell-like environment accelerates the nucleation step of amyloidogenic
      protein misfolding.
AB  - To understand the role of a crowded physiological environment in the pathogenesis
      of neurodegenerative diseases, we report the following. 1) The formation of
      fibrous aggregates of the human Tau fragment Tau-(244-441), when
      hyperphosphorylated by glycogen synthase kinase-3beta, is dramatically
      facilitated by the addition of crowding agents. 2) Fibril formation of
      nonphosphorylated Tau-(244-441) is only promoted moderately by macromolecular
      crowding. 3) Macromolecular crowding dramatically accelerates amyloid formation
      by human prion protein. A sigmoidal equation has been used to fit these kinetic
      data, including published data of human alpha-synuclein, yielding lag times and
      apparent rate constants for the growth of fibrils for these amyloidogenic
      proteins. These biochemical data indicate that crowded cell-like environments
      significantly accelerate the nucleation step of fibril formation of human Tau
      fragment/human prion protein/human alpha-synuclein (a significant decrease in the
      lag time). These results can in principle be predicted based on some known data
      concerning protein concentration effects on fibril formation both in vitro and in
      vivo. Furthermore, macromolecular crowding causes human prion protein to form
      short fibrils and nonfibrillar particles with lower conformational stability and
      higher protease resistance activity, compared with those formed in dilute
      solutions. Our data demonstrate that a crowded physiological environment could
      play an important role in the pathogenesis of neurodegenerative diseases by
      accelerating amyloidogenic protein misfolding and inducing human prion fibril
      fragmentation, which is considered to be an essential step in prion replication.

PMID- 19748896
TI  - Novel Bcl-2 homology-3 domain-like sequences identified from screening randomized
      peptide libraries for inhibitors of the pro-survival Bcl-2 proteins.
AB  - Interactions between Bcl-2 homology-3 (BH3)-only proteins and their pro-survival
      Bcl-2 family binding partners initiate the intrinsic apoptosis pathway. These
      interactions are mediated by a short helical motif, the BH3 domain, on the BH3
      only protein, which inserts into a hydrophobic groove on the pro-survival
      molecule. To identify novel peptidic ligands that bind Mcl-1, a pro-survival
      protein relative of Bcl-2, both human and mouse Mcl-1 were screened against large
      randomized phage-displayed peptide libraries. We identified a number of 16-mer
      peptides with sub-micromolar affinity that were highly selective for Mcl-1, as
      well as being somewhat selective for the species of Mcl-1 (human or mouse)
      against which the library was panned. Interestingly, these sequences all strongly
      resembled natural BH3 domain sequences. By switching residues within the best of
      the human Mcl-1-binding sequences, or extending beyond the core sequence
      identified, we were able to alter the pro-survival protein interaction profile of
      this peptide such that it now bound all members tightly and was a potent killer
      when introduced into cells. Introduction of an amide lock constraint within this
      sequence also increased its helicity and binding to pro-survival proteins. These
      data provide new insights into the determinants of BH3 domain:pro-survival
      protein affinity and selectivity.

PMID- 19748897
TI  - Suppression of human T-cell leukemia virus I gene expression by pokeweed
      antiviral protein.
AB  - Human T-cell leukemia virus I (HTLV-I) is a deltaretrovirus that is the causative
      agent of adult T-cell leukemia and the neurological disorder HTLV-I-associated
      myelopathy/tropical spastic paraparesis. Currently, no effective antiretroviral
      treatment options are available to restrict the development of diseases
      associated with the virus. In this work, we investigated the activity of pokeweed
      antiviral protein (PAP) on HTLV-I, when expressed from a proviral clone in 293T
      cells or in an HTLV-I immortalized cell line. PAP is a plant-derived N
      glycosidase that exhibits antiviral activity against a number of viruses;
      however, its mode of action has not been clearly defined. Here, we describe the
      mechanism by which PAP inhibited production of HTLV-I. We show that PAP
      depurinated nucleotides within the gag open reading frame and suppressed the
      synthesis of viral proteins in part by decreasing the translational efficiency of
      HTLV-I gag/pol mRNA. Observed reduction in levels of viral mRNAs were not due to
      enhanced degradation; rather, decreased amounts of viral transactivator protein,
      Tax, led to feed-back inhibition of transcription from the viral promoter.
      Therefore, PAP efficiently suppressed HTLV-I gene expression at both
      translational and transcriptional levels, resulting in substantially diminished
      virus production. Significantly, no changes in viability or rates of cellular
      transcription or translation were observed in cells expressing PAP, indicating
      that this protein was not toxic. Antiviral activity, together with the absence of
      cytotoxicity, supports further investigation of this enzyme as a novel
      therapeutic agent against the progression of HTLV-I infection.

PMID- 19748898
TI  - The mammalian Hsp40 ERdj3 requires its Hsp70 interaction and substrate-binding
      properties to complement various yeast Hsp40-dependent functions.
AB  - Heat shock proteins of 70 kDa (Hsp70s) and their J domain-containing Hsp40
      cofactors are highly conserved chaperone pairs that facilitate a large number of
      cellular processes. The observation that each Hsp70 partners with many J domain
      containing proteins (JDPs) has led to the hypothesis that Hsp70 function is
      dictated by cognate JDPs. If this is true, one might expect highly divergent
      Hsp70-JDP pairs to be unable to function in vivo. However, we discovered that,
      when a yeast cytosolic JDP, Ydj1, was targeted to the mammalian endoplasmic
      reticulum (ER), it interacted with the ER-lumenal Hsp70, BiP, and bound to BiP
      substrates. Conversely, when a mammalian ER-lumenal JDP, ERdj3, was directed to
      the yeast cytosol, it rescued the temperature-sensitive growth phenotype of yeast
      containing mutant alleles in two cytosolic JDPs, HLJ1 and YDJ1, and activated the
      ATP hydrolysis rate of Ssa1, the yeast cytosolic Hsp70 that partners with Hlj1
      and Ydj1. Surprisingly, ERdj3 mutants that were compromised for substrate binding
      were unable to rescue the hlj1ydj1 growth defect even though they stimulated the
      ATPase activity of Ssa1. Yet, J domain mutants of ERdj3 that were defective for
      interaction with Ssa1 restored the growth of hlj1ydj1 yeast. Taken together,
      these data suggest that the substrate binding properties of certain JDPs, not
      simply the formation of unique Hsp70-JDP pairs, are critical to specify in vivo
      function.

PMID- 19748899
TI  - Pseudofungi: coral shapes and bamboo sticks in lymph node sinuses.

PMID- 19748900
TI  - Treatment outcomes for severe feeding problems in children with autism spectrum
      disorder.
AB  - There is abundant research to support that children with autism spectrum disorder
      (ASD) exhibit challenging feeding behaviors. Despite increase in empirical
      evidence supporting the role of behavior analysis in treating severe feeding
      problems, evaluation of the short- and long-term effects of these treatments for
      a large group of children with ASD is warranted. The purpose of the current study
      was to evaluate treatment outcomes of an interdisciplinary feeding program for 46
      children with ASD. A retrospective chart analysis indicated these children were
      treated successfully overall and follow-up data suggest gains were maintained
      following discharge from the program.

PMID- 19748901
TI  - Successful PDGFR-{alpha}/{beta} targeting with imatinib in uterine sarcoma.

PMID- 19748902
TI  - Successful salvage high-dose chemotherapy and autologous stem-cell
      transplantation in HIV-related germ-cell tumor.

PMID- 19748903
TI  - Validity of self-reported birth weight by adult women: sociodemographic
      influences and implications for life-course studies.
AB  - Life-course epidemiologic studies frequently obtain data on perinatal and
      childhood factors through adult self-report. Data from a prospective US birth
      cohort of 262 women, born between 1959 and 1963 (average age at adult follow-up,
      41.8 years), were used to assess the validity of self-reported birth weight
      category by sociodemographic characteristics. The effect of reporting error on
      the associations of birth weight with childhood and adult body mass index was
      evaluated by comparing the estimates of associations from linear regression
      analyses. The level of agreement between the birth weight category reported by
      85% of the participants and the birth weight recorded at the time of birth was
      moderate to good (sensitivity = 73%, weighted kappa = 0.67). The validity varied
      by birth weight category (sensitivity range = 58%-81% for the lowest and highest
      birth weight category, respectively) and was highest for participants who were
      white, of lower childhood family income, and born to older mothers. Despite this
      moderate to good validity, the associations of birth weight with childhood and
      adult body mass index were attenuated and no longer statistically significant
      when self-reported birth weight was used. In conclusion, birth weight reported in
      middle adult life is measured with error, limiting its utility for detecting
      modest associations with health in later life periods.

PMID- 19748904
TI  - Function of sperm chromatin structural elements in fertilization and development.
AB  - Understanding how DNA is packaged in the mammalian sperm cell has important
      implications for human infertility as well as for the cell biology. Recent
      advances in the study of mammalian sperm chromatin structure and function have
      altered our perception of this highly condensed, inert chromatin. Sperm DNA is
      packaged very tightly to protect the DNA during the transit that occurs before
      fertilization. However, this condensation cannot sacrifice chromosomal elements
      that are essential for the embryo to access the correct sequences of the paternal
      genome for proper initiation of the embryonic developmental program. The primary
      levels of the sperm chromatin structure can be divided into three main
      categories: the large majority of DNA is packaged by protamines, a smaller amount
      (2-15%) retains histone-bound chromatin and the DNA is attached to the nuclear
      matrix at roughly 50 kb intervals. Current data suggest that the latter two
      structural elements are transferred to the paternal pronucleus after
      fertilization where they have important functional roles. The nuclear matrix
      organization is essential for DNA replication, and the histone-bound chromatin
      identifies genes that are important for embryonic development. These data support
      the emerging view of the sperm genome as providing, in addition to the paternal
      DNA sequence, a structural framework that includes molecular regulatory factors
      that are required for proper embryonic development.

PMID- 19748905
TI  - Naive CD4 T cells from aged mice show enhanced death upon primary activation.
AB  - Poor T cell immunity is one of the many defects seen in elderly humans and aged
      (Ad) mice. We report that naive CD4 T cells from aged mice (ANCD4 cells) showed
      greater apoptosis upon primary activation than those from young (Yg) mice, with
      loss of mitochondrial membrane potential, poor activation of Rel family
      transcription factors and increased DNA damage. Their ability to enhance
      glycolysis, produce lactate and induce autophagy following activation was also
      compromised. ANCD4 cells remained susceptible to death beyond first cell
      division. Activated ANCD4 cells also showed poor transition to a 'central memory'
      (CM) CD44(high), CD62L(high) phenotype in vitro. This correlated with low
      proportions of CM cells in Ad mice in vivo. Functionally, too, IFN-gamma
      responses recalled from T cells of immunized Ad mice, poor to begin with,
      worsened with time as compared with Yg mice. Thus, ANCD4 cells handle activation
      associated stress very poorly due to multiple defects, possibly contributing to
      poor formation of long-lasting memory.

PMID- 19748906
TI  - Endothelin signalling in arterial smooth muscle is tightly regulated by G protein
      coupled receptor kinase 2.
AB  - AIMS: Prolonged endothelin (ET) receptor signalling causes vasoconstriction and
      can lead to hypertension, vascular smooth muscle hypertrophy, and hyperplasia.
      Usually, G protein-coupled receptor signalling is negatively regulated by G
      protein-coupled receptor kinases (GRKs), preventing prolonged or inappropriate
      signalling. This study investigated whether GRKs regulate ET receptor contractile
      signalling in adult Wistar rat mesenteric arterial smooth muscle cells (MSMCs).
      METHODS AND RESULTS: ET-1-stimulated phospholipase C (PLC) activity and changes
      in [Ca2+]i were assessed using confocal microscopy in rat MSMCs transfected with
      the pleckstrin-homology domain of PLCdelta1 (eGFP-PH) and loaded with Fura-Red.
      ET-1 applications (30 s) stimulated transient concentration-dependent eGFP-PH
      translocations from plasma membrane to cytoplasm and graded [Ca2+]i increases. ET
      1-mediated PLC signalling was blocked by the type A endothelin receptor (ET(A)R)
      antagonist, BQ123. To characterize ET(A)R desensitization, cells were stimulated
      with a maximally effective concentration of ET-1 (50 nM, 30 s) followed by a
      variable washout period and a second identical application of ET-1. This brief
      exposure to ET-1 markedly decreased ET(A)R responsiveness to re-challenge, and
      reversal was incomplete even after increasing the time period between agonist
      challenges to 60 min. To assess GRK involvement in ET(A)R desensitization, MSMCs
      were co-transfected with eGFP-PH and catalytically inactive (D110A,K220R)GRK2,
      (D110A,K220R)GRK3, (K215R)GRK5, or (K215R)GRK6 constructs. (D110A,K220R)GRK2
      expression significantly attenuated ET(A)R desensitization, whereas other
      constructs were ineffective. Small interfering RNA-targeted GRK2 depletion
      equally attenuated ET(A)R desensitization. Finally, immunocyotchemical data
      showed that ET(A)R activation recruited endogenous GRK2 from cytoplasm to
      membrane. CONCLUSION: These studies identify GRK2 as a key regulator of ET(A)R
      responsiveness in resistance arteries, highlighting the potential importance of
      this GRK isoenzyme in regulating vasoconstrictor signalling pathways implicated
      in vascular disease.

PMID- 19748907
TI  - Nutrient and growth responses of cattail (Typha domingensis) to redox intensity
      and phosphate availability.
AB  - BACKGROUND AND AIMS: In the Florida Everglades, the expansion of cattail (Typha
      domingensis) into areas once dominated by sawgrass (Cladium jamaicense) has been
      attributed to altered hydrology and phosphorus (P) enrichment. The objective of
      this study was to quantify the interactive effects of P availability and soil
      redox potential (Eh) on the growth and nutrient responses of Typha, which may
      help to explain its expansion. METHODS: The study examined the growth and
      nutrient responses of Typha to the interactive effects of P availability (10, 80
      and 500 microg P L(-1)) and Eh level (-150, +150 and +600 mV). Plants were grown
      hydroponically in a factorial experiment using titanium (Ti(3+)) citrate as a
      redox buffer. KEY RESULTS: Relative growth rate, elongation, root-supported
      tissue/root ratio, leaf length, lateral root length and biomass, as well as
      tissue nutrient concentrations, were all adversely affected by low Eh conditions.
      P availability compensated for the negative effect of low Eh for all these
      variables except that low P stimulated root length and nutrient use efficiency.
      The most growth-promoting treatment combination was 500 microg P L(-1)/ + 600 mV.
      CONCLUSIONS: These results, plus previous data on Cladium responses to P/Eh
      combinations, document that high P availability and low Eh should benefit Typha
      more than Cladium as the growth and tissue nutrients of the former species
      responded more to excess P, even under highly reduced conditions. Therefore, the
      interactive effects of P enrichment and Eh appear to be linked to the expansion
      of Typha in the Everglades Water Conservation Area 2A, where both low Eh and
      enhanced phosphate availability have co-occurred during recent decades.

PMID- 19748908
TI  - Phenology, growth and physiological adjustments of oil palm (Elaeis guineensis)
      to sink limitation induced by fruit pruning.
AB  - BACKGROUND AND AIMS: Despite its simple architecture and small phenotypic
      plasticity, oil palm has complex phenology and source-sink interactions.
      Phytomers appear in regular succession but their development takes years,
      involving long lag periods between environmental influences and their effects on
      sinks. Plant adjustments to resulting source-sink imbalances are poorly
      understood. This study investigated oil palm adjustments to imbalances caused by
      severe fruit pruning. METHODS: An experiment with two treatments (control and
      complete fruit pruning) during 22 months in 2006-2008) and six replications per
      treatment was conducted in Indonesia. Phenology, growth of above-ground
      vegetative and reproductive organs, leaf morphology, inflorescence sex
      differentiation, dynamics of non-structural carbohydrate reserves and light
      saturated net photosynthesis (A(max)) were monitored. KEY RESULTS: Artificial
      sink limitation by complete fruit pruning accelerated development rate, resulting
      in higher phytomer, leaf and inflorescence numbers. Leaf size and morphology
      remained unchanged. Complete fruit pruning also suppressed the abortion of male
      inflorescences, estimated to be triggered at about 16 months before bunch
      maturity. The number of female inflorescences increased after an estimated lag of
      24-26 months, corresponding to time from sex differentiation to bunch maturity.
      The most important adjustment process was increased assimilate storage in the
      stem, attaining nearly 50 % of dry weight in the stem top, mainly as starch,
      whereas glucose, which in controls was the most abundant non-structural
      carbohydrate stored in oil palm, decreased. CONCLUSIONS: The development rate of
      oil palm is in part controlled by source-sink relationships. Although increased
      rate of development and proportion of female inflorescences constituted observed
      adjustments to sink limitation, the low plasticity of plant architecture
      (constant leaf size, absence of branching) limited compensatory growth. Non
      structural carbohydrate storage was thus the main adjustment process.

PMID- 19748909
TI  - Phenology and growth adjustments of oil palm (Elaeis guineensis) to photoperiod
      and climate variability.
AB  - BACKGROUND AND AIMS: Oil palm flowering and fruit production show seasonal maxima
      whose causes are unknown. Drought periods confound these rhythms, making it
      difficult to analyse or predict dynamics of production. The present work aims to
      analyse phenological and growth responses of adult oil palms to seasonal and
      inter-annual climatic variability. METHODS: Two oil palm genotypes planted in a
      replicated design at two sites in Indonesia underwent monthly observations during
      22 months in 2006-2008. Measurements included growth of vegetative and
      reproductive organs, morphology and phenology. Drought was estimated from
      climatic water balance (rainfall - potential evapotranspiration) and simulated
      fraction of transpirable soil water. Production history of the same plants for
      2001-2005 was used for inter-annual analyses. KEY RESULTS: Drought was absent at
      the equatorial Kandista site (0 degrees 55'N) but the Batu Mulia site (3 degrees
      12'S) had a dry season with variable severity. Vegetative growth and leaf
      appearance rate fluctuated with drought level. Yield of fruit, a function of the
      number of female inflorescences produced, was negatively correlated with
      photoperiod at Kandista. Dual annual maxima were observed supporting a recent
      theory of circadian control. The photoperiod-sensitive phases were estimated at 9
      (or 9 + 12 x n) months before bunch maturity for a given phytomer. The main
      sensitive phase for drought effects was estimated at 29 months before bunch
      maturity, presumably associated with inflorescence sex determination. CONCLUSION:
      It is assumed that seasonal peaks of flowering in oil palm are controlled even
      near the equator by photoperiod response within a phytomer. These patterns are
      confounded with drought effects that affect flowering (yield) with long time-lag.
      Resulting dynamics are complex, but if the present results are confirmed it will
      be possible to predict them with models.

PMID- 19748910
TI  - Assessment of sentinel lymph node in cervical cancer: review of literature.
AB  - Sentinel lymph node biopsy is a novel method for the surgical management of
      patients with cervical cancer. Sentinel nodes have a higher chance of harbouring
      metastases than non-sentinel nodes. Assessment of sentinel nodes provides an
      opportunity to stage patients intraoperatively and avoid complete pelvic lymph
      node dissection and hence its morbidities. The aim of this article is to review
      the diagnostic performance of sentinel node detection, to determine which
      technique (blue dye, Tc or both) has the highest detection rate and sensitivity,
      and also to illustrate different approaches of histological assessment of the
      sentinel lymph node biopsy.

PMID- 19748911
TI  - Antisense expression of mitochondrial ATP synthase subunits OSCP (ATP5) and gamma
      (ATP3) alters leaf morphology, metabolism and gene expression in Arabidopsis.
AB  - Determination of the role of mitochondrial (mt) ATP synthesis in plant metabolism
      is complicated by chloroplastic ATP synthesis. To differentiate ATP synthesis
      from these two organelles, we created transgenic Arabidopsis plants in which two
      different subunits of the mt ATP synthase, the oligomycin sensitivity-conferring
      protein (OSCP) (=delta) (ATP5) and the gamma (ATP3) subunit, were expressed
      individually in antisense orientation under the control of a dexamethasone
      inducible promoter. The phenotypic effects of antisense expression were identical
      for both atp5 and atp3. Seedling lethality resulted from induction during
      germination in the light, demonstrating the essentiality of both gene products.
      Reduced expression of either gene resulted in stunting of dark-grown (etiolated)
      seedlings, downward curling or wavy-edged leaf margins of light-grown plants and
      ball-shaped unexpanded flowers. Antisense induction reduced total ATP levels in
      dark-grown (etiolated) seedlings germinated on media lacking sucrose, but
      increased total ATP levels in induced light-grown plants and in induced dark
      grown seedlings germinated on media containing sucrose. Induction reduced
      transcript levels for two transcription factors (TCP3 and TCP4) whose decreased
      expression is associated with a similar wavy-edged leaf phenotype in Arabidopsis,
      and increased transcript levels for dynamin-related proteins whose increased
      expression is associated with increased mt division. Reduced expression of these
      subunits of the mt ATP synthase is proposed to disturb cellular redox states,
      which ultimately manifest downstream as diverse and seemingly unrelated
      phenotypes.

PMID- 19748912
TI  - Seasonal and long-term effects of CO2 and O3 on water loss in ponderosa pine and
      their interaction with climate and soil moisture.
AB  - Evapotranspiration (ET) is driven by evaporative demand, available solar energy
      and soil moisture (SM) as well as by plant physiological activity which may be
      substantially affected by elevated CO2 and O3. A multi-year study was conducted
      in outdoor sunlit-controlled environment mesocosm containing ponderosa pine
      seedlings growing in a reconstructed soil-litter system. The study used a 2 x 2
      factorial design with two concentrations of CO2 (ambient and elevated), two
      levels of O3 (low and high) and three replicates of each treatment. The objective
      of this study was to assess the effects of chronic exposure to elevated CO2 and
      O3, alone and in combination, on daily ET. This study evaluated three hypotheses:
      (i) because elevated CO2 stimulates stomatal closure, O3 effects on ET will be
      less under elevated CO2 than under ambient CO2; (ii) elevated CO2 will ameliorate
      the long-term effects of O3 on ET; and (iii) because conductance (g) decreases
      with decreasing SM, the impacts of elevated CO2 and O3, alone and in combination,
      on water loss via g will be greater in early summer when SM is not limiting than
      to other times of the year. A mixed-model covariance analysis was used to adjust
      the daily ET for seasonality and the effects of SM and photosynthetically active
      radiation when testing for the effects of CO2 and O3 on ET via the vapor pressure
      deficit gradient. The empirical results indicated that the interactive stresses
      of elevated CO2 and O3 resulted in a lesser reduction in ET via reduced canopy
      conductance than the sum of the individual effects of each gas. CO2-induced
      reductions in ET were more pronounced when trees were physiologically most
      active. O3-induced reductions in ET under ambient CO2 were likely transpirational
      changes via reduced conductance because needle area and root biomass were not
      affected by exposures to elevated O3 in this study.

PMID- 19748913
TI  - In vitro evaluation of five rapid antigen detection tests for group A beta
      haemolytic streptococcal sore throat infections.
AB  - BACKGROUND: Using accurate and easy to use rapid antigen detection tests (RADTs)
      to identify group A beta-haemolytic Streptococci (GABHS) sore throat infections
      could reduce unnecessary antibiotic prescribing and antimicrobial resistance.
      Although there is no international consensus on the use of RADTs, these kits have
      been widely adopted in Finland, France and the USA. Yet in the UK, the Clinical
      Knowledge Summaries, that provide the main online guidance for GPs, discourage
      RADTs use, citing their poor sensitivity and inability to impact on prescribing
      decisions in acute sore throat infections. OBJECTIVE: The purpose of this study
      was to evaluate the ease of use and in vitro accuracy (sensitivity and
      specificity) of the five most commonly used RADTs in Europe (OSOM Ultra, Quickvue
      Dipstick, Streptatest, Clearview Exact Strep A and IMI Test Pack). METHODS: To
      ensure the RADTs were evaluated objectively, a standardized in vitro method using
      known concentrations of GABHS was used to remove the inherent biases associated
      with clinical studies. RESULTS: The IMI Test Pack was the easiest RADT to use
      overall. The ability to detect all positive GABHS (sensitivity) varied
      considerably between kits from 95% [95% confidence interval (CI): 88-98%], for
      the IMI Test Pack and OSOM, to 62% (95% CI: 51-72%) for Clearview, at the highest
      GABHS concentration. None of the RADTs gave any false-positive results with
      commensal flora-they were 100% specific. CONCLUSIONS: The IMI Test Pack is most
      suitable for use in primary care, as it had high sensitivity, high specificity
      and was easy to use.

PMID- 19748914
TI  - A comparison of chronic illness care quality in US and UK family medicine
      practices prior to pay-for-performance initiatives.
AB  - BACKGROUND: The Quality and Outcomes Framework (QOF) has contributed to modest
      improvements in chronic illness care in the UK. US policymakers have proposed
      similar pay-for-performance (P4P) approaches to improve care. Since previous
      studies have not compared chronic illness care quality in US and UK primary care
      practices prior to the QOF, the relative preparedness of practices to respond to
      P4P incentives is unknown. OBJECTIVE: To compare US and UK practices on P4P
      measures prior to program implementation. METHODS: We analysed medical record
      data collected before QOF implementation from randomly selected patients with
      diabetes or coronary artery disease (CAD) in 42 UK and 55 US family medicine
      practices. We compared care processes and intermediate outcomes using
      hierarchical logistic regression. RESULTS: While we found gaps in chronic illness
      care quality across both samples, variation was lower in UK practices. UK
      patients were more likely to receive recommended care processes for diabetes
      [odds ratio (OR), 8.94; 95% confidence interval (CI), 4.26-18.74] and CAD (OR,
      9.18; 95% CI, 5.22-16.17) but less likely to achieve intermediate diabetes
      outcome targets (OR, 0.50; 95% CI, 0.39-0.64). CONCLUSIONS: Following National
      Health Service (NHS) investment in primary care preparedness, but prior to the
      QOF, UK practices provided more standardized care but did not achieve better
      intermediate outcomes than a sample of typical US practices. US policymakers
      should focus on reducing variation in care documentation to ensure the
      effectiveness of P4P efforts while the NHS should focus on moving from process
      documentation to better patient outcomes.

PMID- 19748915
TI  - The metabolic role of the legume endosperm: a noninvasive imaging study.
AB  - Although essential for normal seed development in the legumes, the metabolic role
      of the endosperm remains uncertain. We designed noninvasive nuclear magnetic
      resonance tools for the in vivo study of key metabolites in the transient liquid
      endosperm of intact pea (Pisum sativum) seeds. The steady-state levels of
      sucrose, glutamine, and alanine could be monitored and their distribution within
      the embryo sac visualized. Seed structure was digitalized as a three-dimensional
      model, providing volume information for distinct seed organs. The nuclear
      magnetic resonance method, combined with laser microdissection, isotope labeling,
      in situ hybridization, and electron microscopy, was used to contrast the wild
      type endosperm with that of a mutant in which embryo growth is retarded.
      Expression of sequences encoding amino acid and sucrose transporters was up
      regulated earlier in the endosperm than in the embryo, and this activity led to
      the accumulation of soluble metabolites in the endosperm vacuole. The endosperm
      provides a temporary source of nutrition, permits space for embryo growth, and
      acts as a buffer between the maternal organism and its offspring. The
      concentration of sucrose in the endosperm vacuole is developmentally controlled,
      while the total amount accumulated depends on the growth of the embryo. The
      endosperm concentration of glutamine is a limiting factor for protein storage.
      The properties of the endosperm ensure that the young embryo develops within a
      homeostatic environment, necessary to sustain embryogenesis. We argue for a
      degree of metabolite-mediated control exerted by the endosperm on the growth of,
      and assimilate storage by, the embryo.

PMID- 19748916
TI  - Unique features of plant cleavage and polyadenylation specificity factor revealed
      by proteomic studies.
AB  - Cleavage and polyadenylation of precursor mRNA is an essential process for mRNA
      maturation. Among the 15 to 20 protein factors required for this process, a
      subgroup of proteins is needed for both cleavage and polyadenylation in plants
      and animals. This subgroup of proteins is known as the cleavage and
      polyadenylation specificity factor (CPSF). To explore the in vivo structural
      features of plant CPSF, we used tandem affinity purification methods to isolate
      the interacting protein complexes for each component of the CPSF subunits using
      Arabidopsis (Arabidopsis thaliana ecotype Landsberg erecta) suspension culture
      cells. The proteins in these complexes were identified by mass spectrometry and
      western immunoblots. By compiling the in vivo interaction data from tandem
      affinity purification tagging as well as other available yeast two-hybrid data,
      we propose an in vivo plant CPSF model in which the Arabidopsis CPSF possesses
      AtCPSF30, AtCPSF73-I, AtCPSF73-II, AtCPSF100, AtCPSF160, AtFY, and AtFIPS5. Among
      them, AtCPSF100 serves as a core with which all other factors, except AtFIPS5,
      are associated. These results show that plant CPSF possesses distinct features,
      such as AtCPSF73-II and AtFY, while sharing other ortholog components with its
      yeast and mammalian counterparts. Interestingly, these two unique plant CPSF
      components have been associated with embryo development and flowering time
      controls, both of which involve plant-specific biological processes.

PMID- 19748917
TI  - Arabidopsis LON2 is necessary for peroxisomal function and sustained matrix
      protein import.
AB  - Relatively little is known about the small subset of peroxisomal proteins with
      predicted protease activity. Here, we report that the peroxisomal LON2
      (At5g47040) protease facilitates matrix protein import into Arabidopsis
      (Arabidopsis thaliana) peroxisomes. We identified T-DNA insertion alleles
      disrupted in five of the nine confirmed or predicted peroxisomal proteases and
      found only two-lon2 and deg15, a mutant defective in the previously described
      PTS2-processing protease (DEG15/At1g28320)-with phenotypes suggestive of
      peroxisome metabolism defects. Both lon2 and deg15 mutants were mildly resistant
      to the inhibitory effects of indole-3-butyric acid (IBA) on root elongation, but
      only lon2 mutants were resistant to the stimulatory effects of IBA on lateral
      root production or displayed Suc dependence during seedling growth. lon2 mutants
      displayed defects in removing the type 2 peroxisome targeting signal (PTS2) from
      peroxisomal malate dehydrogenase and reduced accumulation of 3-ketoacyl-CoA
      thiolase, another PTS2-containing protein; both defects were not apparent upon
      germination but appeared in 5- to 8-d-old seedlings. In lon2 cotyledon cells,
      matrix proteins were localized to peroxisomes in 4-d-old seedlings but
      mislocalized to the cytosol in 8-d-old seedlings. Moreover, a PTS2-GFP reporter
      sorted to peroxisomes in lon2 root tip cells but was largely cytosolic in more
      mature root cells. Our results indicate that LON2 is needed for sustained matrix
      protein import into peroxisomes. The delayed onset of matrix protein sorting
      defects may account for the relatively weak Suc dependence following germination,
      moderate IBA-resistant primary root elongation, and severe defects in IBA-induced
      lateral root formation observed in lon2 mutants.

PMID- 19748918
TI  - A magic bullet for gout?

PMID- 19748919
TI  - Can MRI substitute for biopsy in eosinophilic fasciitis?

PMID- 19748920
TI  - IgM-rheumatoid factor and anti-cyclic citrullinated peptide decrease by 50%
      during intensive treatment in early rheumatoid arthritis.

PMID- 19748921
TI  - Effects of a 3-month course of rosuvastatin in patients with systemic lupus
      erythematosus.

PMID- 19748922
TI  - Paraspinal and intraspinal calcinosis: frequent complications in patients with
      systemic sclerosis.

PMID- 19748923
TI  - The effect of air abrasion preparation on the shear bond strength of an
      orthodontic bracket bonded to enamel.
AB  - The purpose of this study was to determine the method of preparation of enamel
      which best retains a bonded orthodontic bracket against a shear force. Two
      hundred and twelve human lower premolars were randomly divided into four equal
      groups. Group 1 underwent no air abrasion, group 2 received treatment with 25
      microm aluminium oxide particles, group 3 with 50 microm particles, and group 4
      with 100 microm particles. All groups were treated with a self-etching primer
      before bonding of an orthodontic bracket. Each tooth was tested in a JJ Lloyd
      M30K machine to determine the maximum shear force required to dislodge the
      bracket from the tooth. A one-way analysis of variance test conducted at a 95
      percent confidence level (CL) demonstrated that there was a significant
      difference (P < 0.01) with respect to the four methods of preparation of the
      enamel surface. An unpaired t-test was then applied at a 95 percent CL. There was
      no statistically significant difference between groups 1 and 2. There was,
      however, a statistically significant difference between groups 1 and 3 (P <
      0.01), as well as between groups 1 and 4 (P < 0.01). In addition, there was
      significant difference found between groups 2 and 3 (P < 0.05), groups 2 and 4 (P
      < 0.01), and groups 3 and 4 (P < 0.05).

PMID- 19748924
TI  - Longitudinal profile changes in an Anatolian Turkish population.
AB  - The goal of this study was to assess longitudinal changes in the facial soft
      tissue profile in relation to age and gender in young Anatolian Turkish subjects.
      A total of 30 subjects (15 females and 15 males) with an Angle Class I occlusal
      relationship and normal antero-posterior (ANB, 2-4 degrees) skeletal
      relationships were selected from the archive of Dicle University. All subjects
      were of Anatolian Turkish heritage, and none had any apparent facial disharmony
      or had undergone orthodontic therapy. Lateral cephalometric radiographs taken at
      T1 (mean age 8.8 years), T2 (mean age 13.8 years), and T3 (mean age 17.8 years)
      were separately investigated. Non-gender-specific research was also carried out
      at the same time periods. In total, 24 measurements were analysed longitudinally.
      Differences between the genders were determined using independent t-tests.
      Repeated measures analysis of variance tests were used to evaluate repeated
      measurements, and paired sample t-tests to compare inside effects between the
      genders. Significant increases (P < 0.05) were found with age for both females
      and males. Generally, the increases were greater in males than in females. Nasal
      prominence increased more than chin prominence, resulting in a tendency to have
      convex profiles.

PMID- 19748926
TI  - Involvement of p29 in DNA damage responses and Fanconi anemia pathway.
AB  - Human p29 is a chromatin-associated protein and the silencing of p29 expression
      increases cell population in G(1) phase and decreases phosphorylation levels of
      Chk1 and Chk2 in response to UV treatment. To further characterize the function
      of p29, U2OS and Fanconi anemia complementation group G (FA-G) cells with
      constitutive p29 expression have been established. Analyses of these cells
      identified increased phosphorylation levels of Chk1 and Chk2, which were
      accompanied by elevated amounts of chromatin-associated Mre11-Rad50-Nbs1 complex
      and ATR-IP. Monoubiquitination of the FA ID complex was restored in p29 stably
      expressing FA-G cells. Moreover, lower tumor incidence was observed in mp29
      transgenic mice after UV irradiation. These results suggest the involvement of
      p29 in the DNA damage responses and Fanconi anemia pathway.

PMID- 19748925
TI  - Cancer-preventive activities of tocopherols and tocotrienols.
AB  - The cancer-preventive activity of vitamin E has been studied. Whereas some
      epidemiological studies have suggested a protective effect of vitamin E against
      cancer formation, many large-scale intervention studies with alpha-tocopherol
      (usually large doses) have not demonstrated a cancer-preventive effect. Studies
      on alpha-tocopherol in animal models also have not demonstrated robust cancer
      prevention effects. One possible explanation for the lack of demonstrable cancer
      preventive effects is that high doses of alpha-tocopherol decrease the blood and
      tissue levels of delta-tocopherols. It has been suggested that gamma-tocopherol,
      due to its strong anti-inflammatory and other activities, may be the more
      effective form of vitamin E in cancer prevention. Our recent results have
      demonstrated that a gamma-tocopherol-rich mixture of tocopherols inhibits colon,
      prostate, mammary and lung tumorigenesis in animal models, suggesting that this
      mixture may have a high potential for applications in the prevention of human
      cancer. In this review, we discuss biochemical properties of tocopherols, results
      of possible cancer-preventive effects in humans and animal models and possible
      mechanisms involved in the inhibition of carcinogenesis. Based on this
      information, we propose that a gamma-tocopherol-rich mixture of tocopherols is a
      very promising cancer-preventive agent and warrants extensive future research.

PMID- 19748927
TI  - Alteration of microRNA expression in vinyl carbamate-induced mouse lung tumors
      and modulation by the chemopreventive agent indole-3-carbinol.
AB  - MicroRNAs (miRNAs) are small, non-protein-coding RNAs that can function as tumor
      suppressors or oncogenes. Deregulation of miRNA expression has been reported in
      lung cancer. However, modulation of miRNA expression by chemopreventive agents
      remains to be defined. In the present study, we examined if the chemopreventive
      agent indole-3-carbinol (I3C) reversed vinyl carbamate (VC)-induced deregulation
      of miRNA levels in lung tissues of female A/J mice. Lung tissues were obtained
      from a previous chemoprevention study, in which mice were treated with VC and
      given I3C in the diet for 15 weeks. Microarray studies revealed alterations in
      the expression of a number of miRNAs in lung tumors relative to that of normal
      lungs. miR-21, mir-31, miR-130a, miR-146b and miR-377 were consistently
      upregulated, whereas miR-1 and miR-143 were downregulated in lung tumors relative
      to normal lungs. In mice treated with VC and given I3C in the diet, levels of miR
      21, mir-31, miR-130a, miR-146b and miR-377 were reduced relative to the level in
      mice treated with the carcinogen only. The results of the microarray study were
      confirmed by quantitative reverse transcription-polymerase chain reaction and gel
      analysis of polymerase chain reaction products. Further studies with miR-21
      indicated that phosphatase and tensin homolog, programmed cell death 4 and rich
      protein with Kazal motifs are potential targets for the oncogenic effect of miR
      21 and the chemopreventive activity of I3C. Taken together, we showed here that
      miRNAs are deregulated during VC-induced mouse lung tumorigenesis and their
      levels are modulated by I3C. Therefore, miRNAs and their target genes are
      promising biomarkers for the diagnosis of lung cancer and efficacy of
      chemopreventive/chemotherapeutic agents.

PMID- 19748928
TI  - Pro-survival of estrogen receptor-negative breast cancer cells is regulated by a
      BLT2-reactive oxygen species-linked signaling pathway.
AB  - Leukotriene B4 (LTB4) is an inflammatory mediator with potent biological
      activities in the pathogenesis of many inflammatory diseases. In the present
      study, we found that expression of BLT2, a low-affinity LTB4 receptor, is
      significantly upregulated in breast cancer cells. In addition, we observed that
      inhibition of BLT2 by a specific antagonist, LY255283, or by siBLT2 RNA
      interference caused dramatic apoptotic cell death in breast cancer cells,
      especially in the estrogen receptor (ER)-negative MDA-MB-468 and MDA-MB-453
      cells, suggesting a role for BLT2 in survival of these breast cancer cells. In an
      approach to understand the downstream mechanism by which BLT2 mediates the
      potential pro-survival signaling, we found that the elevated reactive oxygen
      species (ROS) generation is associated with BLT2-mediated survival. Expression of
      Nox1, a member of the NADPH oxidase family, is also highly upregulated in a BLT2
      dependent manner in these breast cancer cells, suggesting that 'Nox1-derived ROS'
      lie downstream of BLT2. Consistent with the proposed role of 'Nox1-ROS' in pro
      survival signaling, knockdown of Nox1 with siNox1 or treatment with a ROS
      scavenging agent caused dramatic apoptotic death in these breast cancer cells.
      Taken together, our results demonstrate, for the first time, that the 'BLT2-Nox1
      ROS'-linked cascade is involved in the pro-survival signaling, especially in ER
      negative breast cancer cells.

PMID- 19748929
TI  - Timing of brain damage and verbal-performance IQ tilts.

PMID- 19748930
TI  - The evolution of amastin surface glycoproteins in trypanosomatid parasites.
AB  - Amastin is a transmembrane glycoprotein found on the cell surfaces of
      trypanosomatid parasites. Encoded by a large, diverse gene family, amastin was
      initially described from the intracellular, amastigote stage of Trypanosoma cruzi
      and Leishmania donovani. Genome sequences have subsequently shown that the
      amastin repertoire is much larger in Leishmania relative to Trypanosoma. However,
      it is not known when this expansion occurred, whether it is associated with the
      origins of Leishmania and vertebrate parasitism itself, or prior to this. To
      examine the timing of amastin diversification, as well as the evolutionary
      mechanisms regulating gene repertoire and sequence diversity, this study
      sequenced the genomic regions containing amastin loci from two related insect
      parasites (Leptomonas seymouri and Crithidia sp.) and estimated a phylogeny for
      these and other amastin sequences. The phylogeny shows that amastin includes four
      subfamilies with distinct genomic positions, secondary structures, and evolution,
      which were already differentiated in the ancestral trypanosomatid.
      Diversification in Leishmania was initiated from a single ancestral locus on
      chromosome 34, with rapid derivation of novel loci through transposition and
      accelerated sequence divergence. This is absent from related organisms showing
      that diversification occurred after the origin of Leishmania. These results
      describe a substantial elaboration of amastin repertoire directly associated with
      the origin of Leishmania, suggesting that some amastin genes evolved novel
      functions crucial to cell function in leishmanial parasites after the acquisition
      of a vertebrate host.

PMID- 19748931
TI  - Adaptive evolution of digestive RNASE1 genes in leaf-eating monkeys revisited:
      new insights from ten additional colobines.
AB  - Pancreatic RNase genes implicated in the adaptation of the colobine monkeys to
      leaf eating have long intrigued evolutionary biologists since the identification
      of a duplicated RNASE1 gene with enhanced digestive efficiencies in Pygathrix
      nemaeus. The recent emergence of two contrasting hypotheses, that is, independent
      duplication and one-duplication event hypotheses, make it into focus again.
      Current understanding of Colobine RNASE1 gene evolution of colobine monkeys
      largely depends on the analyses of few colobine species. The present study with
      more intensive taxonomic and character sampling not only provides a clearer
      picture of Colobine RNASE1 gene evolution but also allows to have a more thorough
      understanding about the molecular basis underlying the adaptation of Colobinae to
      the unique leaf-feeding lifestyle. The present broader and detailed phylogenetic
      analyses yielded two important findings: 1) All trees based on the analyses of
      coding, noncoding, and both regions provided consistent evidence, indicating
      RNASE1 duplication occurred after Asian and African colobines speciation, that
      is, independent duplication hypothesis; 2) No obvious evidence of gene conversion
      in RNASE1 gene was found, favoring independent evolution of Colobine RNASE1 gene
      duplicates. The conclusion drawn from previous studies that gene conversion has
      played a significant role in the evolution of Colobine RNASE1 was not supported.
      Our selective constraint analyses also provided interesting insights, with
      significant evidence of positive selection detected on ancestor lineages leading
      to duplicated gene copies. The identification of a handful of new adaptive sites
      and amino acid changes that have not been characterized previously also provide a
      necessary foundation for further experimental investigations of RNASE1 functional
      evolution in Colobinae.

PMID- 19748932
TI  - Antibiotic resistance patterns and serotype distribution in Streptococcus
      pneumoniae from hospitalized pediatric patients with respiratory infections in
      Suzhou, China.

PMID- 19748933
TI  - Molecular and epidemiological trend of sapovirus, and astrovirus infection in
      Japan.

PMID- 19748934
TI  - A first-order simulator to control dioxin emissions: NMCRC-ATMOS.
AB  - Dioxins are highly toxic halogenated organic compounds formed as an unintentional
      by-product of many industrial processes involving chlorine and combustion. At the
      Negev Monte Carlo Research Center (NMCRC) and the Green Processes Center at the
      Shamoon College of Engineering (SCE), Israel, we have developed a code for the
      first-order estimation of dioxin emissions from waste incinerators and the
      subsequent atmospheric dispersion. The NMCRC-ATMOS (Atmospheric Evaluator)
      program will allow public planners and facility operators to estimate and predict
      the effect of current and potential waste incineration facilities on nearby
      population centres. This information can also be used by plant operators to
      decide whether to run the facilities at maximum capacity based on weather
      conditions. With the NMCRC-ATMOS tool, the user has the ability to easily
      establish location-based fallout from the average conditions (both facility and
      atmospheric) surrounding the waste incineration plant. This program currently
      focuses on dioxin emissions from waste incinerators, but can eventually be
      expanded to include other emission sources and atmospheric effects, as well as
      internet connectivity for real-time data acquisition. NMCRC-ATMOS is a Windows
      program that has been tested on Windows XP Service Pack 2 with the .NET Framework
      2.0 installed.

PMID- 19748935
TI  - Vinegar production residue as substrates for phytase production by Aspergillus
      ficuum.
AB  - Two kinds of vinegar production residues, sorghum vinegar residue (SVR) and corn
      vinegar residue (CVR), were used as a substrate for phytase production in solid
      state fermentation (SSF) by Aspergillus ficuum. Various process parameters
      influencing phytase production were evaluated by single factor design
      experiments; further study involved CVR and its goodness-of-fit levels. An
      incubation time of 48 hours, initial moisture of 55% and an inoculum of 1.2 x
      10(7) spores per millilitre were the optimum cultural conditions for the
      production of phytase in waste corn vinegar residue, without adding in vitro
      nutrient elements by orthogonal design experiment. Results showed that vinegar
      production residue as substrates for phytase production by Aspergillus ficuum
      through microbiology fermentation could be applied to treatment of an integrated
      system for waste from vinegar processing.

PMID- 19748936
TI  - Solvent extraction of organic acids from stillage for its re-use in ethanol
      production process.
AB  - Stillage re-use in the fermentation stage in ethanol production is a technique
      used for the reduction of water and fermentation nutrients consumption. However,
      the inhibitory effect on yeast growth of the by-products and feed components that
      remains in stillage increases with re-use and reduces the number of possible
      recycles. Several methods such as ultrafiltration, electrodialysis and advanced
      oxidation processes have been used in stillage treatment prior its re-use in the
      fermentation stage. Nevertheless, few studies evaluating the effect of solvent
      extraction as a stillage treatment option have been performed. In this work, the
      inhibitory effect of serial stillage recycling over ethanol and biomass
      production was determined, using acetic acid as a monitoring compound during the
      fermentation and solvent extraction process. Raw palm oil methyl ester showed the
      highest acetic acid extraction from the aqueous phase, presenting a distribution
      coefficient of 3.10 for a 1:1 aqueous phase mixture:solvent ratio. Re-using
      stillage without treatment allowed up to three recycles with an ethanol
      production of 53.7 +/- 2.0 g L(-1), which was reduced 25% in the fifth recycle.
      Alternatively, treated stillage allowed up to five recycles with an ethanol final
      concentration of 54.7 +/- 1.3 g L(- 1). These results show that reduction of
      acetic acid concentration by an extraction process with raw palm oil methyl ester
      before re-using stillage improves the number of recycles without a major effect
      on ethanol production. The proposed process generates a palm oil methyl ester
      that contains organic acids, among other by-products, that could be used for
      product recovery and as an alternative fuel.

PMID- 19748937
TI  - Effect of biosolids on refuse decomposition and phosphorus cycling.
AB  - Laboratory-scale reactors containing mixtures of municipal solid waste and
      wastewater treatment biosolids were monitored to assess the effect of biosolids
      on refuse decomposition and on phosphorus (P) cycling and speciation among
      orthophosphate, acid-hydrolysable P, and organic P. The co-disposal of 10 to 20%
      (by wet weight) aerobically-digested biosolids with residential refuse was
      compatible with refuse decomposition although the biosolids did not increase
      either the maximum methane production rate or the cumulative yield, and did not
      reduce lag times to the onset of methane production. The results of this study
      indicated that dissolved reactive phosphorus (DRP) was the dominant dissolved P
      fraction throughout refuse decomposition and that it was negatively correlated
      with the methane production rate and pH (r2 = 0.35 for both). P was not found to
      limit methane production. Biosolids increased dissolved P as well as ammonia-N in
      some reactors, but this did not have a significant impact on maximum methane
      production rates. The maximum tolerated Na+ and K+ concentrations during active
      methane production were at least 4100 mg Na+ L-1 and 800 mg K+ L-1, respectively.

PMID- 19748938
TI  - Experimental design and process analysis for acidic leaching of metal-rich glass
      wastes.
AB  - The removal of iron, titanium and aluminium from colourless and green waste
      glasses has been studied under various experimental conditions in order to
      optimize the process parameters and to decrease the metal content in the waste
      glass by acidic leaching. Statistical design of experiments and ANOVA (analysis
      of variance) were performed in order to determine the main effects and
      interactions between the investigated factors (sample ratio, acid concentration,
      temperature and leaching time). A full factorial experiment was performed by
      sulphuric acid leaching of glass for metal removal. After treating, the iron
      content was 530 ppm, corresponding to 1880 ppm initial concentration of Fe(2)O(3)
      in the original colourless sample. This result is achieved using 1M H(2)SO( 4)
      and 30% sample ratio at 90(o)C leaching temperature for 2 hours. The iron content
      in the green waste glass sample was reduced from 3350 ppm initial concentration
      to 2470 ppm after treating.

PMID- 19748939
TI  - Incineration and co-combustion of waste: accounting of greenhouse gases and
      global warming contributions.
AB  - Important greenhouse gas (GHG) emissions related to waste incineration and co
      combustion of waste were identified and considered relative to critical aspects
      such as: the contents of biogenic and fossil carbon, N(2)O emissions, fuel and
      material consumptions at the plants, energy recovery, and solid residues
      generated. GHG contributions were categorized with respect to direct emissions
      from the combustion plant as well as indirect upstream contributions (e.g.
      provision of fuels and materials) and indirect downstream contributions (e.g.
      substitution of electricity and heat produced elsewhere). GHG accounting was done
      per tonne of waste received at the plant. The content of fossil carbon in the
      input waste, for example as plastic, was found to be critical for the overall
      level of the GHG emissions, but also the energy conversion efficiencies were
      essential. The emission factors for electricity provision (also substituted
      electricity) affected the indirect downstream emissions with a factor of 3-9
      depending on the type of electricity generation assumed. Provision of auxiliary
      fuels, materials and resources corresponded to up to 40% of the direct emission
      from the plants (which were 347-371 kg CO(2)-eq. tonne( -1) of waste for
      incineration and 735-803 kg CO(2)-eq. tonne(-1) of waste for co-combustion).
      Indirect downstream savings were within the range of -480 to -1373 kg CO(2)eq.
      tonne(-1) of waste for incineration and within -181 to -2607 kg CO(2)-eq. tonne(-
      1) of waste for co-combustion. N(2)O emissions and residue management did not
      appear to play significant roles.

PMID- 19748940
TI  - Characteristics of fine processed construction and demolition waste in Japan and
      method to obtain fines having low gypsum component and wood contents.
AB  - A method to obtain processed residue from mixed construction and demolition waste
      (mixed C&D-W) - free from environmental pollutants - for deposition in landfill
      is discussed. In particular, additional sieving, the presence of gypsum board in
      mixed C&D-W at the first stage of manual presorting, and the color of processed
      residue were studied for the basic characterization of the different fractions.
      Considerable precautions should be taken to prevent leaching of hazardous
      substances, such as T-Hg, Pb, Cr(6+), As, and fluoride and its compounds, when
      processed residue, particularly in crushed fraction at an intermediate treatment
      facility, is used as construction material. A relatively high content of gypsum
      was noted in processed residue generated at demolition work compared to that
      generated at construction work in processed residue from mixed C&D-W in which the
      presence of gypsum board was observed at the first stage of manual presorting,
      and in white processed residue. Additional sieving for removal was ineffective
      because gypsum and wood have wide particle size distributions. To obtain
      processed residue having low gypsum and wood contents, white processed residue
      should be removed to eliminate gypsum (content, 59% of initial sample), and brown
      or brown and yellow processed residue should be removed to eliminate wood
      (content, 32% of initial sample) without mixing with processed residue containing
      other colors at stockyards. The removed residue should be deposited in a
      controlled-type landfill site.

PMID- 19748941
TI  - Climate impact analysis of waste treatment scenarios--thermal treatment of
      commercial and pretreated waste versus landfilling in Austria.
AB  - A major challenge for modern waste management lies in a smart integration of
      waste-to-energy installations in local energy systems in such a way that the
      energy efficiency of the waste-to-energy plant is optimized and that the energy
      contained in the waste is, therefore, optimally utilized. The extent of
      integration of thermal waste treatment processes into regular energy supply
      systems plays a major role with regard to climate control. In this research, the
      specific waste management situation looked at scenarios aiming at maximizing the
      energy recovery from waste (i.e. actual scenario and waste-to-energy process with
      75% energy efficiency [22.5% electricity, 52.5% heat]) yield greenhouse gas
      emission savings due to the fact that more greenhouse gas emissions are avoided
      in the energy sector than caused by the various waste treatment processes.
      Comparing dedicated waste-to-energy-systems based on the combined heat and power
      (CHP) process with concepts based on sole electricity production, the energy
      efficiency proves to be crucial with regard to climate control. This underlines
      the importance of choosing appropriate sites for waste-to-energy-plants. This
      research was looking at the effect with regard to the climate impact of various
      waste management scenarios that could be applied alternatively by a private waste
      management company in Austria. The research is, therefore, based on a specific
      set of data for the waste streams looked at (waste characteristics, logistics
      needed, etc.). Furthermore, the investigated scenarios have been defined based on
      the actual available alternatives with regard to the usage of treatment plants
      for this specific company. The standard scenarios for identifying climate impact
      implications due to energy recovery from waste are based on the respective
      marginal energy data for the power and heat generation facilities/industrial
      processes in Austria.

PMID- 19748942
TI  - Condominium waste management by private initiative: a report of a 10-year project
      in Brazil.
AB  - The evolution of domestic waste management practices in an urban residential
      condominium complex in Brazil is reported. A sustained effort over 10 years has
      created a benchmark for landfill diversion by private initiative. The project was
      initiated in 1998 when the prevailing practice was to tip all waste at the
      landfill. In the presently attained situation, which is available for imitation
      elsewhere, 67% of all domestic waste produced in the complex is recycled without
      cost to the municipal administration. Instead of separating the inert
      recyclables, the effort was turned to separating the biodegradable material. The
      management programme derived from waste analyses and the work with people evolved
      into a two-stage source-separation procedure combined with the participation of
      handpicked reverse logistics operators. City crews now take only 33% of all waste
      to the landfill. Although this description is strictly valid only for Brazil, the
      story in itself might be of wider interest.

PMID- 19748943
TI  - Recycling of plastic: accounting of greenhouse gases and global warming
      contributions.
AB  - Major greenhouse gas (GHG) emissions related to plastic waste recycling were
      evaluated with respect to three management alternatives: recycling of clean,
      single-type plastic, recycling of mixed/contaminated plastic, and use of plastic
      waste as fuel in industrial processes. Source-separated plastic waste was
      received at a material recovery facility (MRF) and processed for granulation and
      subsequent downstream use. In the three alternatives, plastic was assumed to be
      substituting virgin plastic in new products, wood in low-strength products
      (outdoor furniture, fences, etc.), and coal or fuel oil in the case of energy
      utilization. GHG accounting was organized in terms of indirect upstream emissions
      (e.g. provision of energy, fuels, and materials), direct emissions at the MRF
      (e.g. fuel combustion), and indirect downstream emissions (e.g. avoided emissions
      from production of virgin plastic, wood, or coal/oil). Combined, upstream and
      direct emissions were estimated to be roughly between 5 and 600 kg CO(2)-eq.
      tonne( -1) of plastic waste depending on treatment at the MRF and CO(2) emissions
      from electricity production. Potential downstream savings arising from
      substitution of virgin plastic, wood, and energy fuels were estimated to be
      around 60- 1600 kg CO(2)-eq. tonne( -1) of plastic waste depending on
      substitution ratios and CO(2) emissions from electricity production. Based on the
      reviewed data, it was concluded that substitution of virgin plastic should be
      preferred. If this is not viable due to a mixture of different plastic types
      and/or contamination, the plastic should be used for energy utilization.
      Recycling of plastic waste for substitution of other materials such as wood
      provided no savings with respect to global warming.

PMID- 19748944
TI  - Characterization of oily sludge from a Tehran oil refinery.
AB  - In this study, oily sludge samples generated from a Tehran oil refinery (Pond I)
      were evaluated for their contamination levels and to propose an adequate
      remediation technique for the wastes. A simple, random, sampling method was used
      to collect the samples. The samples were analyzed to measure Total petroleum
      hydrocarbon (TPH), polyaromatic hydrocarbon (PAH) and heavy metal concentrations
      in the sludge. Statistical analysis showed that seven samples were adequate to
      assess the sludge with respect to TPH analyses. The mean concentration of TPHs in
      the samples was 265,600 mg kg-1. A composite sample prepared from a mix of the
      seven samples was used to determine the sludge's additional characteristics.
      Composite sample analysis showed that there were no detectable amounts of PAHs in
      the sludge. In addition, mean concentrations of the selected heavy metals Ni, Pb,
      Cd and Zn were 2700, 850, 100, 6100 mg kg-1, respectively. To assess the sludge
      contamination level, the results from the analysis above were compared with soil
      clean-up levels. Due to a lack of national standards for soil clean-up levels in
      Iran, sludge pollutant concentrations were compared with standards set in
      developed countries. According to these standards, the sludge was highly polluted
      with petroleum hydrocarbons. The results indicated that incineration, biological
      treatment and solidification/stabilization treatments would be the most
      appropriate methods for treatment of the sludges. In the case of
      solidification/stabilization, due to the high organic content of the sludge, it
      is recommended to use organophilic clays prior to treatment of the wastes.

PMID- 19748945
TI  - Evaluation of primary and secondary production using wastewater as a culture
      medium.
AB  - The ability of rotifers and cladocerans to convert primary to secondary
      production in wastewaters was tested. Scenedesmus acutus was cultured on Bold's
      (defined) medium, wastewater from the tertiary phase of water treatment and a
      mixture of both. The algal growth rates (u) ranged from 0.4 to 0.7 day-1, being
      highest in defined medium. The demographic characteristics of Brachionus rubens
      and Moina macrocopa were tested using algae at a density of 1.0 x 106 cells mL-1.
      Into each test jar, we introduced 20 neonates (< 12-h-old) of either B. rubens or
      M. macrocopa. Daily (for M. macrocopa) or twice a day (for B. rubens), dead
      adults and the neonates were enumerated and removed. Average life-span and
      generation time of B. rubens were not significantly influenced by the algal
      treatment type. Gross and net reproductive rates were significantly influenced by
      the medium on which the algae was cultured; in the case of B. rubens, they ranged
      from 20-36 and 10-22 offspring female-1; the corresponding values for M.
      macrocopa were higher (38-110 and 13-31 offspring female-1, respectively). The
      rate of population increase was higher for Brachionus (0.41-0.65 day-1)) compared
      to Moina (0.28-0.57 day-1). Brachionus had significantly higher growth rates on
      algae cultured on Bold medium than on treated wastewater while Moina grew
      significantly better on Scenedesmus cultured on Bold medium or a mixture of
      treated wastewater and Bold medium than on treated wastewater alone.

PMID- 19748946
TI  - An environmentally viable waste disposal method for oil-producing countries.
AB  - The increasing amount of oil field waste is a matter of concern. This study
      proposes the Slurry Fracture Injection (SFI) technique as an alternative waste
      disposal method. The proposed waste disposal method is complete and leaves few
      future liabilities. The entire waste can be injected into an isolated deep
      geologic zone with no contamination of water-bearing formations or formations
      outside the targeted zone. The method can lead to the reclamation of oil industry
      landfills and the oil pits and dumps. We propose a two-tiered screening method
      for evaluating the feasibility of this technology and identification of a
      suitable target zone. A stringent environmental monitoring program should
      complement the SFI process to ensure environmental compatibility.

PMID- 19748947
TI  - Change of crystallinity and mineral composition of fly ash with mechanical and
      chemical activation for the improvement of phosphate uptake.
AB  - A detailed investigation of the development of the mineral composition and
      crystallinity of fly ash (FA) activated by an integrated process, as well as the
      relation between that development and phosphate uptake (PU) in solution, was
      conducted. This process, consisting of pretreatment (mechanical milling), alkali
      fusion (sodium hydroxide) at 550  degrees C and acid attack (3 mol L-1 sulfuric
      acid), exhibited a remarkable activation effect. One-hour grinding could enhance
      PU from 0.67 to 1.66 mg PO43--P g-1 FA, and then under the optimum chemical
      conditions with the ratio of NaOH to FA of 0.5 g g-1 and that of H2SO4 to FA of 3
      mL g-1, the PU was further improved to 7.14 mg g-1. Results also indicated that
      the PU performance was closely linked with the crystallinity and mineral
      composition of FA, that is, the treated material with the lowest crystallinity
      and least crystal phase could achieve the highest PU. For the purpose of
      destroying original minerals in raw FA farthest and avoiding the production of
      new crystals, therefore, control on the ratio of NaOH to FA and that of acid to
      FA was very important during the chemical treatment.

PMID- 19748948
TI  - Greenhouse gases, radiative forcing, global warming potential and waste
      management--an introduction.
AB  - Management of post-consumer solid waste contributes to emission of greenhouse
      gases (GHGs) representing about 3% of global anthropogenic GHG emissions. Most
      GHG reporting initiatives around the world utilize two metrics proposed by the
      Intergovernmental Panel on Climate Change (IPCC): radiative forcing (RF) and
      global warming potential (GWP). This paper provides a general introduction of the
      factors that define a GHG and explains the scientific background for estimating
      RF and GWP, thereby exposing the lay reader to a brief overview of the methods
      for calculating the effects of GHGs on climate change. An objective of this paper
      is to increase awareness that the GWP of GHGs has been re-adjusted as the
      concentration and relative proportion of these GHGs has changed with time (e.g.,
      the GWP of methane has changed from 21 to 25 CO(2)-eq). Improved understanding of
      the indirect effects of GHGs has also led to a modification in the methodology
      for calculating GWP. Following a presentation of theory behind GHG, RF and GWP
      concepts, the paper briefly describes the most important GHG sources and sinks in
      the context of the waste management industry. The paper serves as a primer for
      more detailed research publications presented in this special issue of Waste
      Management & Research providing a technology-based assessment of quantitative GHG
      emissions from different waste management technologies.

PMID- 19748949
TI  - Characterization of MSW and related waste-derived compost in Zanzibar
      municipality.
AB  - The spread of municipal solid waste (MSW) in Zanzibar municipality has been
      associated with environmental pollution, unpleasant city conditions,
      contamination of water sources and coastal areas together with harbouring of
      malaria vectors. The contamination has a close relationship with eruption of
      diarrhoea, cholera and typhoid which claim the lives of the residents. Most of
      the wastes are of domestic and market origin and have the potential for compost
      production. This study examined the possibility of composting MSW from Zanzibar
      municipality as an alternative way of SW management and assessed the nutrient
      contents of the compost for application in agricultural production. Two major
      classes of SW were selected for the study: municipal solid waste and rice milling
      by-products. The samples were composted aerobically and anaerobically. The
      results showed that aerobic composting reduced about 60% of the waste volume.
      This volume reduction suggests that composting can be a promising SW management
      technique by reducing the large demand of space for landfilling. Municipal solid
      waste composted under anaerobic conditions produced compost with relatively
      higher concentrations of dissolved species than that produced under aerobic
      conditions. The trace metal contents were higher in MSW than in rice milling by
      products. It was found that the unmanaged compost collected from the dumping site
      had low nutrient contents and was enriched with trace metals. Generally, physico
      chemical characteristics, nutrients and trace metal levels suggest that Zanzibar
      municipal solid waste can produce high-quality compost for application to a wide
      range of soil types to improve their fertility, under proper management.

PMID- 19748950
TI  - Composting and compost utilization: accounting of greenhouse gases and global
      warming contributions.
AB  - Greenhouse gas (GHG) emissions related to composting of organic waste and the use
      of compost were assessed from a waste management perspective. The GHG accounting
      for composting includes use of electricity and fuels, emissions of methane and
      nitrous oxide from the composting process, and savings obtained by the use of the
      compost. The GHG account depends on waste type and composition (kitchen organics,
      garden waste), technology type (open systems, closed systems, home composting),
      the efficiency of off-gas cleaning at enclosed composting systems, and the use of
      the compost. The latter is an important issue and is related to the long-term
      binding of carbon in the soil, to related effects in terms of soil improvement
      and to what the compost substitutes; this could be fertilizer and peat for soil
      improvement or for growth media production. The overall global warming factor
      (GWF) for composting therefore varies between significant savings (-900 kg CO(2)
      equivalents tonne(-1) wet waste (ww)) and a net load (300 kg CO(2)-equivalents
      tonne( -1) ww). The major savings are obtained by use of compost as a substitute
      for peat in the production of growth media. However, it may be difficult for a
      specific composting plant to document how the compost is used and what it
      actually substitutes for. Two cases representing various technologies were
      assessed showing how GHG accounting can be done when specific information and
      data are available.

PMID- 19748951
TI  - Vermicomposting of sugar industry waste (press mud) mixed with cow dung employing
      an epigeic earthworm Eisenia fetida.
AB  - In India, millions of tons of press mud (PM) are generated by sugar mills every
      year. This paper reports the potential of vermitechnology to convert sugar
      industry waste PM mixed with cow dung (CD) into vermicompost, employing an
      epigeic earthworm Eisenia fetida. A total of six different reactors were
      established having different ratios of PM and CD including one control (CD only).
      The growth and fecundity of E. fetida was monitored for 13 weeks. Maximum growth
      was recorded in 100% CD, but earthworms grew and reproduced favourably up to 1:1
      PM and CD feed composition. However, greater percentages of PM in different
      reactors significantly affected the growth and fecundity of worms.
      Vermicomposting resulted in a decrease in carbon concentration and an increase in
      nitrogen, phosphorus and calcium concentrations of the vermicompost.
      Investigations indicated that vermicomposting could be an alternative technology
      for the management of PM into useful fertilizing material, if mixed at maximum
      50% with CD.

PMID- 19748952
TI  - Characterization and recovery of copper values from discarded slag.
AB  - In any copper smelter large quantities of copper slag are discarded as waste
      material causing space and environmental problems. This discarded slag contains
      important amounts of metallic values such as copper and iron. The recovery of
      copper values from an Indian smelter slag that contains 1.53% Cu, 39.8% Fe and
      34.65% SiO(2) was the focus of the present study. A complete investigation of the
      different phases present in the slag has been carried out by means of optical
      microscopy, Raman spectroscopy, scanning electron microscopy (SEM), and X-ray
      diffraction (XRD) techniques. It is observed that iron and silica are mostly
      associated with the fayalite phase whereas copper is present in both oxide and
      sulfide phases. These oxide and sulfide phases of copper are mostly present
      within the slag phase and to some extent the slag is also embedded inside the
      oxide and sulfide phases. The recovery of copper values from the discarded slag
      has been explored by applying a flotation technique using conventional sodium
      isopropyl xanthate (SIX) as the collector. The effects of flotation parameters
      such as pH and collector concentration are investigated. Under optimum flotation
      conditions, it is possible to achieve 21% Cu with more than 80% recovery.

PMID- 19748953
TI  - Report: New reliable method for the measurement of chlorine in refuse-derived
      fuels through combustion experiments in a pilot plant.
AB  - The calorific values and the chlorine contents of refuse-derived fuels were
      measured in the pilot combustion plant (PCP) by means of combustion experiments
      followed by mass and energy balancing. This plant reaches an increased precision
      by measuring the integrated values throughout the whole experimental period of
      three hours, based on a fuel capacity of 10 kg per test, allowing a more reliable
      measurement of pollutants than for experimental analysis of only a few grams of
      the sample. The combustion experiments are shown for the verification of the
      quality of the chlorine balancing in the PCP. The test evaluation was carried out
      by balancing the inputs and outputs of chlorine in the mass streams, and the
      recovery rates for chlorine were determined. An emission pattern for the chlorine
      is described by the transfer coefficients and via the temporal fluctuation of the
      hydrogen chloride concentration in the flue gas. The results of the combustion
      experiments prove that the balancing via combustion experiments in the PCP
      provides reliable data on the chlorine concentrations in the fuels, and is a new
      and reliable method for measuring polluting chlorine in refuse-derived fuels.

PMID- 19748954
TI  - Bioassessments of anaerobically decomposing organic refuse in laboratory
      lysimeters with and without leachate recycling and pH adjustment.
AB  - In this paper, various microbial characteristics of degrading refuse in three
      lysimeters were compared to bioassess the operating conditions with and without
      leachate recycling and pH adjustment. Laboratory lysimeters with leachate
      recycling produced more gas and took less time to reach the highest methane
      percentage than a lysimeter without leachate recycling. Generally, lysimeters
      with leachate recycling showed high ATP (adenosine triphosphate) contents in the
      leachate. But there were no significant differences in dehydrogenase activities
      among the lysimeters. Leachate of all lysimeters inhibited the bioluminescence
      activities of the strain tested. Bioluminescence activity was more inhibited by
      the lysimeter with no leachate recycling (high inhibition corresponds to high
      toxicity of leachate). Generally, less inhibition was observed in the middle of
      the operation phase, which was related with the biodegradation activity.

PMID- 19748955
TI  - Monitoring of biopile composting of oily sludge.
AB  - This paper describes a bioreactor set-up used to simulate degradation of
      petroleum hydrocarbons in a static biopile. The large-scale test was performed in
      a 28 m(3) custom-designed reactor. Oily sludge (40% by weight, having 7% dry
      matter [DM], and hydrocarbons C(10)-C(40) 160,000 mg kg(-1) DM) was mixed with
      organic-rich amendments - mature oil-compost (40%) and garden waste compost
      (20%). Within the reactor, the temperature and soil gases were monitored
      continuously during 370 days via 24 measurement points. Also, moisture content
      was continuously recorded and airflow through compost mix occasionally measured.
      Three-dimensional ordinary kriging spatial models were created to describe the
      dynamic variations of temperature, air distribution, and hydrocarbon
      concentration. There were large temperature differences in horizontal and
      vertical sections during initial months of composting only. Water content of the
      mixture was uneven by layers, referring on relocation of moisture due to aeration
      and condensation. The air distribution through the whole reactor varied largely
      despite of continuous aeration, while the concentration of O(2) was never reduced
      less than 1-2% on average. The results showed that composting of sludge using
      force-aerated static biopile technology was justified during the first 3-4
      months, after which the masses could be re-mixed and heaped for further
      maturation in low-tech compost windrows. After 370 days of treatment, the content
      of hydrocarbons (C( 10)-C(40)) in the compost mixture was reduced by 68.7%.

PMID- 19748956
TI  - Dental solid and hazardous waste management and safety practices in developing
      countries: Nablus district, Palestine.
AB  - This study investigated the dental waste management practices and safety measures
      implemented by dentists in the Nablus district, Palestine. A comprehensive survey
      was conducted for 97 of the 134 dental clinics to assess the current situation.
      Focus was placed on hazardous waste produced by clinics and the handling,
      storage, treatment and disposal measures taken. Mercury, found in dental amalgam,
      is one of the most problematic hazardous waste. The findings revealed that there
      is no proper separation of dental waste by classification as demanded by the
      World Health Organization. Furthermore, medical waste is often mixed with general
      waste during production, collection and disposal. The final disposal of waste
      ends up in open dumping sites sometimes close to communities where the waste is
      burned. Correct management and safety procedures that could be effectively
      implemented in developing countries were examined. It was concluded that
      cooperation between dental associations, government-related ministries and
      authorities needs to be established, to enhance dental waste management and
      provide training and capacity building programs for all professionals in the
      medical waste management field.

PMID- 19748957
TI  - Anaerobic digestion and digestate use: accounting of greenhouse gases and global
      warming contribution.
AB  - Anaerobic digestion (AD) of source-separated municipal solid waste (MSW) and use
      of the digestate is presented from a global warming (GW) point of view by
      providing ranges of greenhouse gas (GHG) emissions that are useful for
      calculation of global warming factors (GWFs), i.e. the contribution to GW
      measured in CO(2)-equivalents per tonne of wet waste. The GHG accounting was done
      by distinguishing between direct contributions at the AD facility and indirect
      upstream or downstream contributions. GHG accounting for a generic AD facility
      with either biogas utilization at the facility or upgrading of the gas for
      vehicle fuel resulted in a GWF from -375 (a saving) to 111 (a load) kg CO(2)-eq.
      tonne(-1) wet waste. In both cases the digestate was used for fertilizer
      substitution. This large range was a result of the variation found for a number
      of key parameters: energy substitution by biogas, N(2)O-emission from digestate
      in soil, fugitive emission of CH( 4), unburned CH(4), carbon bound in soil and
      fertilizer substitution. GWF for a specific type of AD facility was in the range 
      95 to -4 kg CO(2)-eq. tonne(-1) wet waste. The ranges of uncertainty, especially
      of fugitive losses of CH(4) and carbon sequestration highly influenced the
      result. In comparison with the few published GWFs for AD, the range of our data
      was much larger demonstrating the need to use a consistent and robust approach to
      GHG accounting and simultaneously accept that some key parameters are highly
      uncertain.

PMID- 19748958
TI  - Resource recovery from end-of-life tyres in Greece: a field survey, state-of-art
      and trends.
AB  - Lack of consistent and available information for the entire tyre industry has
      often hindered adequate understanding of current and future issues that need to
      be addressed for improving the sustainable end-of-life tyre management. The aim
      of this paper is to review related best available technologies and techniques for
      Greece, ranging from simple mechanical processing, up to complex multistep,
      mechanochemical and/or thermal treatment. End-of-life tyre management guidelines
      in the form of a manual for supporting future entrepreneurs in this field are
      also discussed. Extensive data mining, classification and inventorying was
      performed, both in the field via questionnaires and in the literature, for the
      purpose of accurately determining Hellenic conditions, in order to pinpoint
      encountered problems, propose interventions and determine new entrepreneurship
      opportunities.

PMID- 19748959
TI  - Utilization potential of silica fume in fired clay bricks.
AB  - Silica fume (SF) is an inorganic waste material which is generated during the
      elemental silicon and ferro-silicon alloy production. Due to the unique
      properties, it is utilized in several industries. However, very little
      information is available on the utilization potential of SF in traditional clay
      brick industry. In this study, the effect of different quantities of SF addition
      on the properties of fired clay brick was investigated. Test samples were
      produced by uniaxial pressing and fired at 800, 900, 1000 and 1100 degrees C. The
      microstructures of the samples were investigated by Scanning Electron Microscopy
      (SEM). The strength of the fired samples at 1000 and 1100 degrees C were
      significantly improved with SF addition. It was concluded that the reactive
      amorphous nature of SF particles enhances the sintering action locally and this
      gives better strength behaviour. SF addition also improved the efflorescence
      behaviour of the bricks. It was concluded that the effect of SF addition on the
      fired clay brick mainly depends on the firing temperature. At low firing
      temperatures, SF addition has a tendency to decrease the bulk density. However at
      higher firing temperatures, SF addition allows better sintering action with a
      drastic increase in bulk density.

PMID- 19748960
TI  - An analysis of municipal solid waste discards in Taiwan based on consumption
      expenditure and policy interventions.
AB  - This paper presents a quantitative methodology and an empirical case study in
      Taiwan on modelling municipal solid waste (MSW) discards based on the consumption
      and MSW policy effects through a simultaneous equation system (SES) model. The
      results indicate that per capita consumption expenditures on 'food', 'household
      appliances' and 'amusement & education' are associated with the changes of the
      discards of most of the waste streams in Taiwan from 1992 to 2004. The developed
      model, meanwhile, identifies the effects of several important MSW policy
      measures. With regard to the model implication, consumers could try to reduce
      their unnecessary consumption, producers may rethink their responsibility on
      reducing MSW discards, and municipalities could evaluate the effectiveness of the
      existing policy measures to improve it upon based on the quantitative analysis.
      The backcasts and estimates of the discards of MSW streams could enable the
      planning, designing and executing of MSW system. The findings of this study would
      facilitate the consumer behaviour and support the policy design towards a low
      waste-discard society.

PMID- 19748961
TI  - Evaluation of recycling programmes in household waste collection systems.
AB  - A case study and a literature review have been carried out to address the two
      questions: how can waste flow data from collection systems be interpreted and
      compared? and which factors are decisive in the results of recycling programmes
      in household waste collection systems? The aim is to contribute to the
      understanding of how recycling programmes affect the quantity of waste and
      sorting activities. It is shown how the results from various waste sorting
      systems can be interpreted and made comparable. A set of waste flow indicators is
      proposed, which together with generic system descriptions can facilitate
      comparisons of different collections systems. The evaluation of collection
      systems depends on the system boundaries and will always be site-specific to some
      degree. Various factors are relevant, e.g. environmental objectives, technical
      function, operating costs, types of recyclable materials collected separately,
      property-close collection or drop-off systems, economic incentives, information
      strategies, residential structure, social codes, etc. Kerbside collection of
      recyclables and weight-based billing led to increased waste sorting activities in
      the case study. Forty-three decisive factors are listed and discussed.

PMID- 19748962
TI  - No evidence for association of the systemic lupus erythematosus-associated ITGAM
      variant, R77H, with rheumatoid arthritis in the Caucasian population.

PMID- 19748963
TI  - Identification of phenotypic discriminating markers for intervertebral disc cells
      and articular chondrocytes.
AB  - OBJECTIVE: The present study was conducted to improve our knowledge of
      intervertebral disc (IVD) cell biology by comparing the phenotype of nucleus
      pulposus (NP) and annulus fibrosus (AF) cells with that of articular chondrocytes
      (ACs). METHODS: Rabbit cells from NP and AF were isolated and their phenotype was
      compared with that of AC by real-time PCR analysis of type I (COL1A1), II
      (COL2A1) and V (COL5A1) collagens, aggrecan transcript (AGC1), matrix Gla protein
      (MGP) and Htra serine peptidase 1 (Htra1). RESULTS: Transcript analysis indicated
      that despite certain similarities, IVD cells exhibit distinct COL2A1/COL1A1 and
      COL2A1/AGC1 ratios as compared with AC. The expression pattern of COL5A1, MGP and
      Htra1 makes it possible to define a phenotypic signature for NP and AF cells.
      CONCLUSIONS: Our study shows that NP and AF cells exhibit a clearly
      distinguishable phenotype from that of AC. Type V collagen, MGP and HtrA1 could
      greatly help to discriminate among NP, AF and AC cells.

PMID- 19748964
TI  - Low prevalence of NOD2 SNPs in Behcet's disease suggests protective association
      in Caucasians.
AB  - OBJECTIVE: It has been shown previously that three nucleotide-binding
      oligomerization domain containing 2 (NOD2) variants (Arg702Trp, Gly908Arg and
      Lue1007fs) are associated with Crohn's disease (CD), a disorder clinically
      resembling Behcet's disease (BD). We studied the frequency of these variants in
      BD patients. METHODS: DNA samples of 200 BD patients [59 Caucasians, 139 Middle
      Easterns (MEs) of Arab descent and 2 Asians] and 520 healthy controls (444
      Caucasians and 76 MEs) were genotyped using a Taqman assay. RESULTS: Both the
      Arg702Trp and Leu1007fs (frameshift) variants were significantly less frequently
      present among BD patients compared with healthy controls (0.5 vs 5.8%; P < 1.10(
      5) and 0.0 vs 1.8%; P < 0.007, respectively). In the Caucasian subpopulation,
      Arg702Trp was significantly less frequent in the BD group as compared with the
      controls (P = 0.04); whereas in the ME subpopulation, a trend was observed (P <
      0.06). CONCLUSIONS: Of the three CD-associated single nucleotide polymorphisms,
      one of the variant NOD2 alleles, was found to be present significantly less in
      Caucasian BD patients.

PMID- 19748965
TI  - Adverse events and efficacy of TNF-alpha blockade with infliximab in patients
      with systemic lupus erythematosus: long-term follow-up of 13 patients.
AB  - OBJECTIVE: To follow-up on all available infliximab-treated SLE patients for
      safety and long-term efficacy in order to extract information that is useful for
      planning appropriate controlled trials with infliximab in SLE. METHODS: We
      analysed charts of six patients treated in an open-label safety trial and seven
      additional patients treated with infliximab on a compassionate care basis for
      uncontrolled SLE organ inflammation. RESULTS: Out of nine patients with lupus
      nephritis, six had a long-term response after four infusions of infliximab in
      combination with AZA, lasting for up to 5 years. All five patients with lupus
      arthritis responded, but this response did not last for >2 months after the last
      infusion. One additional patient had a long-lasting improvement in SLE
      interstitial lung disease. No symptoms suggestive of infliximab-induced SLE
      flares occurred in any patients. Short-term treatment appeared relatively safe,
      but one patient developed deep-vein thrombosis and several infections. Under long
      term therapy, two patients had life-threatening or fatal events, namely CNS
      lymphoma and Legionella pneumonia. Retreatment and treatment without concomitant
      immunosuppression led to drug reactions. CONCLUSIONS: Short-term therapy with
      four infusions of infliximab in combination with AZA was relatively safe, and had
      remarkable long-term efficacy for lupus nephritis and, potentially, also
      interstitial lung disease. Long-term therapy with infliximab, however, was
      associated with severe adverse events in two out of three SLE patients, which may
      have been provoked by infliximab and/or by their long-standing refractory SLE and
      previous therapies.

PMID- 19748966
TI  - Relative proportions of hybrid fibres are unaffected by 6 weeks of running
      exercise in mouse skeletal muscles.
AB  - Hybrid muscle fibres co-expressing two or more myosin heavy chain (MHC) isoforms
      represent a significant proportion of fibres in many muscles, but the prevalence
      and precise composition of these fibres varies significantly among muscles and
      animal species. In the present study, we used a forced running protocol for 6
      weeks to determine the effects of running exercise on the relative proportion of
      hybrid muscle fibre types in mouse muscles. In the course of this experiment, we
      also determined the relative proportions of these fibres in several different
      skeletal muscles, since data about hybrid fibres in the mouse are sparse. We
      found that the proportions of hybrid fibres in mouse muscles varied significantly
      among specific muscles (2-25%), but these proportions were unaffected by 6 weeks
      of forced running exercise. In contrast, weight-bearing muscles significantly
      increased in mass in response to running. These data suggest that hybrid muscle
      fibres are relatively refractory to the effects of moderate exercise and
      represent a stable phenotype in normal mouse muscles. The precise nature and
      physiological function of these fibres remain incompletely understood, but it is
      clear that hybrid fibres represent a common phenotype in many muscles.

PMID- 19748967
TI  - Regulation of the stress response in rats by central actions of glucocorticoids.
AB  - Chronic stress causes elevations in glucocorticoid secretion and also increases
      the incidence of hypertension and other manifestations of cardiovascular disease.
      The extent to which the elevated glucocorticoids mediate the stress-associated
      increase in cardiovascular disease risk is unknown. Chronically elevated
      glucocorticoids can cause hypertension by acting in the periphery, but their
      effects within the brain on blood pressure regulation remain largely unexplored.
      We developed a method to produce selective chronic increases in the endogenous
      glucocorticoid corticosterone or the glucocorticoid receptor antagonist
      mifepristone within the hindbrain region, which includes a key cardiovascular
      regulatory area, the nucleus of the solitary tract (NTS). Experiments were
      performed in male Sprague-Dawley, Wistar-Kyoto (WKY) and borderline hypertensive
      rats (BHR). The results indicate that elevated exogenous corticosterone can act
      within the hindbrain to enhance the arterial pressure response to novel restraint
      stress and to reduce the gain and increase the mid-point of the arterial
      baroreflex. Basal levels of endogenous corticosterone have no effect on the
      arterial pressure response to stress in normotensive rats but enhance this
      response in BHR. Chronic stress-induced increases in baseline corticosterone
      enhance the arterial pressure response to stress in BHR but attenuate the
      adaptation of the response in WKY rats. Furthermore, an elevated corticosterone
      concentration within the hindbrain is necessary but not sufficient to cause
      glucocorticoid-induced hypertension. The effects of corticosterone within the
      hindbrain on blood pressure regulation are mediated in part by the glucocortiocid
      receptor, but are also likely to involve mineralocorticoid receptor-mediated
      effects and NTS catecholaminergic neurons. These data support the hypothesis that
      elevated glucocorticoids acting within the brain probably contribute to the
      adverse effects of stress on cardiovascular health in susceptible people.

PMID- 19748968
TI  - In vivo measurements of muscle specific tension in adults and children.
AB  - To better understand the effects of pubertal maturation on the contractile
      properties of skeletal muscle in vivo, the present study investigated whether
      there are any differences in the specific tension of the quadriceps muscle in 20
      adults and 20 prepubertal children of both sexes. Specific tension was calculated
      as the ratio between the quadriceps tendon force and the sum of the physiological
      cross-sectional area (PCSA) multiplied by the cosine of the angle of pennation of
      each head within the quadriceps muscle. The maximal quadriceps tendon force was
      calculated from the knee extension maximal voluntary contraction (MVC) by
      accounting for EMG-based estimates of antagonist co-activation, incomplete
      quadriceps activation using the interpolation twitch technique and magnetic
      resonance imaging (MRI)-based measurements of the patellar tendon moment arm. The
      PCSA was calculated as the muscle volume, measured from MRI scans, divided by
      optimal fascicle length, measured from ultrasound images during MVC at the
      estimated angle of peak quadriceps muscle force. It was found that the quadriceps
      tendon force and PCSA of men (11.4 kN, 214 cm(2)) were significantly greater than
      those of the women (8.7 kN, 152 cm(2); P < 0.01). Both adult groups had greater
      values than the children (P < 0.01) but there were no differences between boys
      (5.2 kN, 99 cm(2)) and girls (6.1 kN, 102 cm(2)). Agonist activation was greater
      in men and women than in girls (P < 0.05), and antagonist activation was greater
      in men than in boys (P < 0.05). Moment arm length was greater in men than in boys
      or girls and greater in women than in boys (P < 0.05). The angle of pennation did
      not differ between the groups in any of the quadriceps heads. The specific
      tension was similar (P > 0.05) between groups: men, 55 +/- 11 N cm(-2); women,
      57.3 +/- 13 N cm(-2); boys, 54 +/- 14 N cm(-2); and girls, 59.8 +/- 15 N cm(-2).
      These findings indicate that the increased muscle strength with maturation is not
      due to an increase in the specific tension of muscle; instead, it can be
      attributed to increases in muscle size, moment arm length and voluntary
      activation level.

PMID- 19748969
TI  - Role of exercise-induced brain-derived neurotrophic factor production in the
      regulation of energy homeostasis in mammals.
AB  - Brain-derived neurotrophic factor (BDNF) has been shown to regulate neuronal
      development and plasticity and plays a role in learning and memory. Moreover, it
      is well established that BDNF plays a role in the hypothalamic pathway that
      controls body weight and energy homeostasis. Recent evidence identifies BDNF as a
      player not only in central metabolism, but also in regulating energy metabolism
      in peripheral organs. Low levels of BDNF are found in patients with
      neurodegenerative diseases, including Alzheimer's disease and major depression.
      In addition, BDNF levels are low in obesity and independently so in patients with
      type 2 diabetes. Brain-derived neurotrophic factor is expressed in non-neurogenic
      tissues, including skeletal muscle, and exercise increases BDNF levels not only
      in the brain and in plasma, but in skeletal muscle as well. Brain-derived
      neurotrophic factor mRNA and protein expression was increased in muscle cells
      that were electrically stimulated, and BDNF increased phosphorylation of AMP
      activated protein kinase (AMPK) and acetyl coenzyme A carboxylase-beta (ACCbeta)
      and enhanced fatty oxidation both in vitro and ex vivo. These data identify BDNF
      as a contraction-inducible protein in skeletal muscle that is capable of
      enhancing lipid oxidation in skeletal muscle via activation of AMPK. Thus, BDNF
      appears to play a role both in neurobiology and in central as well as peripheral
      metabolism. The finding of low BDNF levels both in neurodegenerative diseases and
      in type 2 diabetes may explain the clustering of these diseases. Brain-derived
      neurotrophic factor is likely to mediate some of the beneficial effects of
      exercise with regard to protection against dementia and type 2 diabetes.

PMID- 19748970
TI  - Capsule endoscopy.

PMID- 19748971
TI  - Does improving quality of care save money?

PMID- 19748975
TI  - Glycan gimmickry by parasitic helminths: a strategy for modulating the host
      immune response?
AB  - Parasitic helminths (worms) co-evolved with vertebrate immune systems to enable
      long-term survival of worms in infected hosts. Among their survival strategies,
      worms use their glycans within glycoproteins and glycolipids, which are abundant
      on helminth surfaces and in their excretory/ secretory products, to regulate and
      suppress host immune responses. Many helminths express unusual and antigenic
      (nonhost-like) glycans, including those containing polyfucose, tyvelose, terminal
      GalNAc, phosphorylcholine, methyl groups, and sugars in unusual linkages. In
      addition, some glycan antigens are expressed that share structural features with
      those in their intermediate and vertebrate hosts (host-like glycans), including
      Le(X) (Galbeta1-4[Fucalpha1-3]GlcNAc-), LDNF (GalNAcbeta1-4[Fucalpha1-3]GlcNAc-),
      LDN (GalNAcbeta1-4GlcNAc-), and Tn (GalNAcalpha1-O-Thr/Ser) antigens. The
      expression of host-like glycan determinants is remarkable and suggests that
      helminths may gain advantages by synthesizing such glycans. The expression of
      host-like glycans by parasites previously led to the concept of "molecular
      mimicry," in which molecules are either derived from the pathogen or acquired
      from the host to evade recognition by the host immune system. However, recent
      discoveries into the potential of host glycan-binding proteins (GBPs), such as C
      type lectin receptors and galectins, to functionally interact with various host
      like helminth glycans provide new insights. Host GBPs through their interactions
      with worm-derived glycans participate in shaping innate and adaptive immune
      responses upon infection. We thus propose an alternative concept termed "glycan
      gimmickry," which is defined as an active strategy of parasites to use their
      glycans to target GBPs within the host to promote their survival.

PMID- 19748976
TI  - Hypoxic regulation of secreted proteoglycans in macrophages.
AB  - Macrophages are prominent in hypoxic areas of atherosclerotic lesions, and their
      secreted proteoglycans (PG), such as versican, can modulate the retention of
      lipoproteins and the activity of enzymes, cytokines, and growth factors involved
      in atherogenesis. In this study, we report the effects of hypoxia on PG secreted
      by human monocyte-derived macrophages (HMDM) and the potential regulation by the
      transcription factor hypoxia-inducible factor (HIF-1alpha and HIF-2alpha). We
      found that versican co-localized with HIF-1alpha in macrophage-rich areas in
      human advanced atherosclerotic lesions. Versican and perlecan mRNA expression
      increased after exposure to 0.5% O(2) (hypoxia) compared with 21% O(2) (control
      cells). Using precursors to GAG biosynthesis combined with immunoabsorption with
      a versican antibody an increased versican synthesis was detected at hypoxia.
      Furthermore, siRNA knockdown of HIF-1alpha and HIF-2alpha in THP-1 cells showed
      that the hypoxic induction of versican and perlecan mRNA expression involved HIF
      signaling. Versican expression was co-regulated by HIF-1alpha and HIF-2alpha but
      expression of perlecan was influenced only by HIF-1alpha and not by HIF-2alpha
      knockdown. The results show that oxygen concentration is an important modulator
      of PG expression in macrophages. This may be a novel component of the complex
      role of macrophages in atherosclerosis.

PMID- 19748977
TI  - Intracellular accumulation of efavirenz and nevirapine is independent of P
      glycoprotein activity in cultured CD4 T cells and primary human lymphocytes.
AB  - BACKGROUND: Interaction of antiretrovirals with drug transporters such as P
      glycoprotein (P-gp), multidrug resistance-associated protein (MRP), breast cancer
      resistance protein (BCRP) and solute carrier organic anion transporter (SLCO) may
      influence the emergence of viral mutants by altering intracellular drug
      concentrations. Here we characterize the effect of transporter expression in a
      variety of cell types such as control CEM, CEM(VBL) (P-gp-overexpressing),
      CEM(E1000) (MRP1-overexpressing), MT4, control MDCKII, MDCKII(MDR1) (P-gp
      overexpressing) and peripheral blood mononuclear cells (PBMCs) on the uptake of
      [(14)C]efavirenz and [(3)H]nevirapine. We also investigated the lipophilicity of
      [(14)C]efavirenz and [(3)H]nevirapine. METHODS: The expression of P-gp, MRP1,
      MRP2, SLCO1A2, 1B1, 1B3, 2B1, 3A1 and 4A1 was assessed by PCR. Inhibitors of P-gp
      (XR9576, GF120918, dipyridamole) and MRP (MK571, frusemide, dipyridamole), and
      SLCO substrate or inhibitor (estrone-3-sulphate or montelukast, respectively)
      were used to study the role of drug transporters in the accumulation of
      [(14)C]efavirenz and [(3)H]nevirapine. Lipophilicity was measured by the
      octanol/saline partition coefficient. RESULTS: CEM cells, MT4 cells and PBMCs
      express various SLCO isoforms, with SLCO3A1 detected in all of the cells. XR9576,
      dipyridamole and GF120918 had no effects on the accumulation of [(14)C]efavirenz,
      while MK571 and frusemide produced variable effects in the cells. The
      accumulation of [(14)C]efavirenz was significantly decreased in all the cells by
      montelukast and estrone-3-sulphate. CONCLUSIONS: P-gp expression had no effect on
      the accumulation of [(14)C]efavirenz and [(3)H]nevirapine. MRP1/2 expression,
      lipophilicity and SLCO-like transporters (possibly SLCO3A1) may have greater
      influence on the accumulation of [(14)C]efavirenz than [(3)H]nevirapine.

PMID- 19748978
TI  - Impaired mast cell activation in gene-targeted mice lacking the serum- and
      glucocorticoid-inducible kinase SGK1.
AB  - The PI3K pathway plays a pivotal role in the stimulation of mast cells. PI3K
      dependent kinases include the serum- and glucocorticoid-inducible kinase 1
      (SGK1). The present study explored the role of SGK1 in mast cell function. Mast
      cells were isolated from bone marrow (BMMC) of SGK1 knockout mice (sgk1(-/-)) and
      their wild-type littermates (sgk1(+/+)). The BMMC number as well as CD117, CD34,
      and FcepsilonRI expression in BMCCs were similar in both genotypes. Upon Ag
      stimulation of the FcepsilonRI receptor, Ca(2+) entry but not Ca(2+) release from
      intracellular stores was markedly impaired in sgk1(-/-) BMMCs. The currents
      through Ca(2+)-activated K+ channels induced by Ag were significantly higher in
      sgk1(+/+) BMMCs than in sgk1(-/-) BMMCs. Treatment with the Ca(2+) ionophore
      ionomycin (1 microM) led to activation of the K+ channels in both genotypes,
      indicating that the Ca(2+)-activated K+ channels are similarly expressed and
      sensitive to activation by Ca(2+) in sgk1(+/+) and sgk1(-/-) BMMCs, and that
      blunted stimulation of Ca(2+)-activated K+ channels was secondary to decreased
      Ca(2+) entry. Ag-IgE-induced degranulation and early IL-6 secretion were also
      significantly blunted in sgk1(-/-) BMMCs. The decrease in body temperature
      following Ag treatment, which reflects an anaphylactic reaction, was
      substantially reduced in sgk1(-/-) mice, pointing to impaired mast cell function
      in vivo. Serum histamine levels measured 30 min after induction of an
      anaphylactic reaction were significantly lower in sgk1(-/-) than in
      sgk1(+/+)mice. The observations reveal a critical role for SGK1 in ion channel
      regulation and the function of mast cells, and thus disclose a completely novel
      player in the regulation of allergic reaction.

PMID- 19748979
TI  - Antitumor IgE adjuvanticity: key role of Fc epsilon RI.
AB  - Working with C57BL/6 mouse tumor models, we had previously demonstrated that
      vaccination with IgE-coated tumor cells can protect against tumor challenge, an
      observation that supports the involvement of IgE in antitumor immunity. The
      adjuvant effect of IgE was shown to result from eosinophil-dependent priming of
      the T cell-mediated adaptive immune response. The protective effect is likely to
      be mediated by the interaction of tumor cell-bound IgE with receptors, which then
      trigger the release of mediators, recruitment of effector cells, cell killing and
      tumor Ag cross-priming. It was therefore of utmost importance to demonstrate the
      strict dependence of the protective effect on IgE receptor activation. First, the
      protective effect of IgE was confirmed in a BALB/c tumor model, in which IgE
      loaded modified VV Ankara-infected tumor cells proved to be an effective cellular
      vaccine. However, the protective effect was lost in Fc(epsilon)RIalpha(-/-) (but
      not in CD23(-/-)) knockout mice, showing the IgE-Fc(epsilo)nRI interaction to be
      essential. Moreover, human IgE (not effective in BALB/c mice) had a protective
      effect in the humanized knockin mouse (Fc(epsilon)RIalpha(-/-)
      hFc(epsilon)RIalpha(+)). This finding suggests that the adjuvant effect of IgE
      could be exploited for human therapeutics.

PMID- 19748980
TI  - Heat shock protein-90 inhibitors increase MHC class I-related chain A and B
      ligand expression on multiple myeloma cells and their ability to trigger NK cell
      degranulation.
AB  - Modulation of the host immune system represents a promising therapeutic approach
      against cancer, including multiple myeloma. Recent findings indicate that the NK
      group 2D (NKG2D)- and DNAX accessory molecule-1 (DNAM-1)-activating receptors
      play a prominent role in tumor recognition and elimination by cytotoxic
      lymphocytes, suggesting that the levels of NKG2D and DNAM-1 ligand expression on
      tumor cells may be a critical factor to improve the immune response against
      cancer. In this study, we tested the effect of 17-allylaminogeldanamycin and
      radicicol, drugs targeting the heat shock protein-90 (HSP-90) chaperone protein
      and displaying antimyeloma activity, on the expression of NKG2D and DNAM-1
      ligands in human myeloma cell lines. We demonstrate that HSP-90 inhibitors are
      able to up-regulate both MHC class I chain-related (MIC) A and MICB protein
      surface and mRNA expression in human myeloma cell lines, without any significant
      effect on the basal expression of the DNAM-1 ligand poliovirus receptor CD155, or
      induction of nectin-2 and UL16-binding proteins. Activation of the transcription
      factor heat shock factor-1 by HSP-90 inhibitors is essential for the up
      regulation of MICA/MICB expression and knockdown of heat shock factor-1 using
      small hairpin RNA interference blocks this effect. Moreover, in vitro and in vivo
      binding of heat shock factor-1 to MICA and MICB promoters indicates that it may
      enhance NKG2D ligand expression at the transcriptional level. Finally, exposure
      to HSP-90 inhibitors renders myeloma cells more efficient to activate NK cell
      degranulation and a blocking Ab specific for NKG2D significantly reduces this
      effect. Thus, these results provide evidence that targeting NKG2D ligands
      expression may be an additional mechanism supporting the antimyeloma activity of
      HSP-90 inhibitors and suggest their possible immunotherapeutic value.

PMID- 19748981
TI  - Killer Ig-like receptor ligand mismatch directs NK cell expansion in vitro.
AB  - NK cell alloreactivity is governed largely through failure to detect self-HLA
      class I ligands by the clonally distributed inhibitory killer Ig-like receptors
      (KIR) expressed on the NK cell surface. In this study, we investigated the extent
      to which HLA class I-KIR interactions influence human NK cell proliferation in
      the allogeneic setting. NK cells were cultured with feeder cells either matched
      or mismatched for inhibitory KIR ligands, the latter lacking one or more ligands
      present in the NK cell donor. In postculture cytotoxicity assays, the ability of
      polyclonal NK cells to kill KIR ligand-mismatched targets was enhanced by
      exposure to appropriately mismatched feeder cells in prior culture. This
      corresponded with an increased frequency of postculture donor NK cells expressing
      a given inhibitory KIR if the allogeneic feeder cells used in the culture lacked
      its ligand. Similar skewing of KIR distribution was seen in clonally expanded NK
      cells. Finally, a flow cytometry-based proliferation assay was used to show KIR
      specific NK cell division in response to missing self. The findings demonstrate
      that KIR distribution among a population of alloresponding peripheral blood NK
      cells is shaped by the HLA class I environment.

PMID- 19748982
TI  - Monocytes from patients with type 1 diabetes spontaneously secrete
      proinflammatory cytokines inducing Th17 cells.
AB  - Autoimmune diseases including type 1 diabetes (T1D) are thought to have a
      Th1/Th17 bias. The underlying mechanisms driving the activation and
      differentiation of these proinflammatory T cells are unknown. We examined the
      monocytes isolated directly from the blood of T1D patients and found they
      spontaneously secreted the proinflammatory cytokines IL-1beta and IL-6, which are
      known to induce and expand Th17 cells. Moreover, these in vivo-activated
      monocytes from T1D subjects induced more IL-17-secreting cells from memory T
      cells compared with monocytes from healthy control subjects. The induction of IL
      17-secreting T cells by monocytes from T1D subjects was reduced in vitro with a
      combination of an IL-6-blocking Ab and IL-1R antagonist. In this study, we report
      a significant although modest increase in the frequency of IL-17-secreting cells
      in lymphocytes from long-term patients with T1D compared with healthy controls.
      These data suggest that the innate immune system in T1D may drive the adaptive
      immune system by expanding the Th17 population of effector T cells.

PMID- 19748983
TI  - TLR3 ligand polyinosinic:polycytidylic acid induces IL-17A and IL-21 synthesis in
      human Th cells.
AB  - TLR3 and TLR9 recognize the pathogen-associated microbial patterns dsRNA and
      unmethylated DNA, respectively. The recent discovery that these receptors also
      recognize endogenous ligands from necrotic material has drawn increased attention
      to their involvement in autoimmunity. Th cell cytokines IL-17A and IL-21 have
      been assigned with pivotal roles in the regulation of such autoimmune diseases.
      IL-17A is the hallmark cytokine of the recently discovered proinflammatory Th
      cell subset T(H)17. By contrast, the expression of IL-21 does not seem to be
      limited to a single distinct Th cell subset. We investigated the expression of IL
      17A and IL-21 in human CD4+ T cells in response to stimulation with the TLR3
      ligand polyinosinic:polycytidylic acid (poly(I:C)) and the TLR9 ligand CpG. We
      discovered that poly(I:C) induced synthesis of both IL-17A and IL-21. Moreover,
      we found that poly(I:C) was able to drive the differentiation of naive Th cells
      into an IL-21 but not into an IL-17A-producing phenotype and did this without
      affecting the levels of transcription factors T-bet, GATA-3, or retinoic acid
      receptor-related orphan receptor C. Finally, we found that the IL-21-producing
      cells that were differentiated in response to poly(I:C) expressed the chemokine
      receptor CXCR3, which is important in the recruitment of T cells into inflamed
      joints in rheumatoid arthritis. This is the first report to show that the TLR3
      ligand poly(I:C) can directly induce the synthesis of IL-17A and IL-21 and drive
      differentiation of human naive CD4+ T cells.

PMID- 19748984
TI  - Discontinued postnatal thymocyte development in sphingosine 1-phosphate-lyase
      deficient mice.
AB  - Circulation of lymphocytes through peripheral lymphoid tissues as well as
      progenitor entry into the thymus and its output of mature T cells are critical
      for normal immune function. Egress of lymphocytes from both peripheral lymphoid
      organs and thymus is dependent on sphingosine 1-phosphate (S1P) gradients. S1P
      lyase 1 (SGPL1) deficiency leads to accumulation of S1P in lymphoid tissues,
      which blocks lymphocyte egress and induces thymus atrophy. In this study, we
      investigated thymocyte development in SGPL1-deficient mice (SGPL1(-/-)), which
      exhibited postnatal discontinuation of early thymocytopoiesis starting at 2 wk
      after birth. SGPL(-/-) thymi showed a loss of developing thymocytes in the thymic
      cortex between 2 and 4 wk of age, whereas mature thymocytes accumulated in the
      medulla. Detailed analysis demonstrated a deficit in thymic early T cell
      progenitors (ETP) as the principal reason for discontinued thymocyte development.
      This developmental block was accompanied by accumulation of ceramides, resulting
      in enhanced apoptosis of developing T cells. Lack of immigration or settlement of
      ETP completely halted thymocyte development. We conclude that increased ceramide
      levels in the thymus of SGPL1(-/-) mice abrogate thymic development postnatally
      by enhanced thymocyte apoptosis and depletion of thymic ETP. Our findings
      indicate that potentially therapeutic immunosuppression by SGPL1 inhibition
      should benefit from monitoring ceramides to prevent their increase to apoptosis-
      inducing levels.

PMID- 19748985
TI  - Temporal regulation of Ig gene diversification revealed by single-cell imaging.
AB  - Rearranged Ig V regions undergo activation-induced cytidine deaminase (AID)
      initiated diversification in sequence to produce either nontemplated or templated
      mutations, in the related pathways of somatic hypermutation and gene conversion.
      In chicken DT40 B cells, gene conversion normally predominates, producing
      mutations templated by adjacent pseudo-V regions, but impairment of gene
      conversion switches mutagenesis to a nontemplated pathway. We recently showed
      that the activator, E2A, functions in cis to promote diversification, and that
      G(1) phase of cell cycle is the critical window for E2A action. By single-cell
      imaging of stable AID-yellow fluorescent protein transfectants, we now
      demonstrate that AID-yellow fluorescent protein can stably localize to the
      nucleus in G(1) phase, but undergoes ubiquitin-dependent proteolysis later in
      cell cycle. By imaging of DT40 polymerized lactose operator-lambda(R) cells, in
      which polymerized lactose operator tags the rearranged lambda(R) gene, we show
      that both the repair polymerase Poleta and the multifunctional factor
      MRE11/RAD50/NBS1 localize to lambda(R), and that lambda(R)/Poleta colocalizations
      occur predominately in G(1) phase, when they reflect repair of AID-initiated
      damage. We find no evidence of induction of gamma-H2AX, the phosphorylated
      variant histone that is a marker of double-strand breaks, and Ig gene conversion
      may therefore proceed by a pathway involving templated repair at DNA nicks rather
      than double-strand breaks. These results lead to a model in which Ig gene
      conversion initiates and is completed or nearly completed in G(1) phase. AID
      deaminates ssDNA, and restriction of mutagenesis to G(1) phase would contribute
      to protecting the genome from off-target attack by AID when DNA replication
      occurs in S phase.

PMID- 19748986
TI  - Developmental switch of the expression of ion channels in human dendritic cells.
AB  - Modulation of the expression and activity of plasma membrane ion channels is one
      of the mechanisms by which immune cells can regulate their intracellular Ca(2+)
      signaling pathways required for proliferation and/or differentiation. Voltage
      gated K+ channels, inwardly rectifying K+ channels, and Ca(2+)-activated K+
      channels have been described to play a major role in controlling the membrane
      potential in lymphocytes and professional APCs, such as monocytes, macrophages,
      and dendritic cells (DCs). Our study aimed at the characterization and
      identification of ion channels expressed in the course of human DC
      differentiation from monocytes. We report in this study for the first time that
      immature monocyte-derived DCs express voltage-gated Na+ channels in their plasma
      membrane. The analysis of the biophysical and pharmacological properties of the
      current and PCR-based cloning revealed the presence of Nav1.7 channels in
      immature DCs. Transition from the immature to a mature differentiation state,
      however, was accompanied by the down-regulation of Nav1.7 expression concomitant
      with the up-regulation of voltage-gated Kv1.3 K+ channel expression. The presence
      of Kv1.3 channels seems to be common for immune cells; hence, selective Kv1.3
      blockers may emerge as candidates for inhibiting various functions of mature DCs
      that involve their migratory, cytokine-secreting, and T cell-activating
      potential.

PMID- 19748987
TI  - Engagement of TLR2 does not reverse the suppressor function of mouse regulatory T
      cells, but promotes their survival.
AB  - TLRs are a class of conserved pattern recognition receptors that are used by
      cells of the innate immune system. Recent studies have demonstrated the
      expression of TLRs on both human and mouse T cells raising the possibility that
      TLRs play a direct role in adaptive immunity. TLR2 is activated primarily by
      bacterial wall components including peptidoglycan and lipoproteins. Several
      studies have shown that mouse regulatory T (Treg) cells express TLR2 and claimed
      that engagement of TLR2 by synthetic ligands reversed their suppressive function.
      In contrary, enhancement of Treg function was observed following engagement of
      TLR2 on human Treg. We have reexamined the expression and function of TLR2 on
      mouse Treg purified from Foxp3-GFP knock-in mice. TLR2 ligation by TLR2 agonist,
      the synthetic bacterial lipoprotein Pam3CSK4, enhanced the proliferative
      responses of both conventional T cells and Treg in response to TLR stimulation in
      the absence of APC. Treatment of Foxp3+ Treg with Pam3CSK4 did not alter their
      suppressive function in vitro or in vivo and did not reduce their level of Foxp3
      expression. An additional effect of TLR2 stimulation of Treg was induction of Bcl
      x(L) resulting in enhanced survival in vitro. Treatment of mice with the TLR2
      agonist enhanced the Ag-driven proliferation of Treg in vivo, but did not abolish
      their ability to suppress the development of experimental autoimmune
      encephalomyelitis. Development of methods to selectively stimulate TLR2 on Treg
      may lead to a novel approaches for the treatment of autoimmune diseases.

PMID- 19748988
TI  - Chicken IgY binds its receptor at the CH3/CH4 interface similarly as the human
      IgA: Fc alpha RI interaction.
AB  - Chicken IgY, the ancestral form of mammalian IgE and IgG, is recognized by the
      high-affinity FcY receptor CHIR-AB1, a member of the leukocyte receptor family.
      In this study, we have characterized the receptor ligand interaction site by
      consecutive truncations of the Fcv IgY domains and mutational analyses of
      selected residues. Using several fusion proteins that linked the human Cgamma2
      and Cgamma3 domains with the Fcv IgY domains, a binding assay revealed that both
      the Fcv3 and Fcv4 domains were essential for the IgY CHIR-AB1 interaction.
      Sequence comparisons of chicken IgY with human IgA demonstrated that 11 of the 19
      contact residues important for the IgA FcalphaRI interaction have been conserved
      in chicken IgY, although the overall amino acid identity is only 34%. Among the
      19 amino acids at respective positions in IgY, the mutation of two residues in
      the Fcv3 and two in the Fcv4 domain completely abolished the IgY to CHIR-AB1
      binding revealed by two independent assays. Three further mutations substantially
      altered the interaction. Molecular modeling on the Cv3 to Cv4 crystal structure
      revealed that all critical residues, although on two domains, are in close
      proximity. The importance of N-linked carbohydrates was demonstrated by the
      failure of the CHIR-AB1 interaction after mutation of the glycosylation site. The
      identification of the IgY Cv3/Cv4 interdomain region as critical for binding to
      CHIR-AB1 significantly enhances our understanding of the IgY receptor interaction
      and allows further conclusions regarding the FcR phylogeny.

PMID- 19748989
TI  - Extracellular ATP acting at the P2X7 receptor inhibits secretion of soluble HLA-G
      from human monocytes.
AB  - Bacterial LPS induces the release of ATP from immune cells. Accruing evidence
      suggests that extracellular ATP participates in the inflammatory response as a
      proinflammatory mediator by activating the inflammasome complex, inducing
      secretion of cytokines (IL-1, IL-18) and cell damaging agents such as oxygen
      radicals, cationic proteins, and metalloproteases. It is not known whether ATP
      can also act as a proinflammatory mediator by inhibiting production of molecules
      down-modulating the immune response. Here, we show that extracellular ATP impairs
      in an IL-10-dependent fashion the expression of the tolerogenic soluble and
      membrane-bound HLA-G Ag in human monocytes. The effect of ATP was mimicked by
      BzATP (3'-O-(4-benzoyl)benzoyl-ATP) and greatly reduced by pretreatment with oATP
      (periodate-oxidized ATP), KN-62 (1-[N,O-bis(5-isoquinoline-sulfonyl)-N-methyl-l
      tyrosyl]-4-phenylpiperazine), and an anti-P2X(7) mAb, thus pointing to a specific
      role of the P2X(7) receptor. The effect of ATP was time- and dose-dependent and
      was not due to a decrease in expression of IL-10 receptor. Inhibition by ATP was
      reverted by supplementation of culture medium with exogenous IL-10. Due to the
      well-known immunosuppressive activity of IL-10 and soluble HLA-G, this novel
      effect of ATP might be relevant for the pathophysiology and therapy of
      inflammatory disorders.

PMID- 19748990
TI  - Defucosylated anti-CCR4 monoclonal antibody exerts potent ADCC against primary
      ATLL cells mediated by autologous human immune cells in NOD/Shi-scid, IL-2R
      gamma(null) mice in vivo.
AB  - There is a lack of suitable small animal models to evaluate human Ab-dependent
      cellular cytotoxicity (ADCC) in vivo, because of the species incompatibility
      between humans and animals or due to nonspecific allogeneic immune reactions. To
      overcome these problems, we established a human tumor-bearing mouse model, using
      NOD/Shi-scid, IL-2Rgamma(null) (NOG) mice as recipients, in which autologous
      human immune cells are engrafted and mediate ADCC but in which endogenous murine
      cells are unable to mediate ADCC. In the present study, we used NOG mice bearing
      primary adult T cell leukemia/lymphoma (ATLL) cells and a therapeutic chimeric
      anti-CCR4 mAb, the Fc region of which is defucosylated to enhance ADCC. We report
      significant antitumor activity in vivo associated with robust ADCC mediated by
      autologous effector cells from the same patients. The present study is the first
      to report a mouse model in which a potent antitumor effect of the therapeutic mAb
      against primary tumor cells is mediated by autologous human immune cells. Human
      autologous ADCC in mice in vivo was confirmed by the depletion of human immune
      cells before ATLL PBMC inoculation. In addition, NOG mice bearing primary ATLL
      cells presented features identical with patients with ATLL. In conclusion, this
      approach makes it possible to model the human immune system active in Ab-based
      immunotherapy in vivo, and thus to perform more appropriate preclinical
      evaluations of novel therapeutic mAb. Furthermore, the potent ADCC mediated by
      defucosylated anti-CCR4 mAb, observed here in vivo in humanized mice, will be
      exploited in clinical trials in the near future.

PMID- 19748991
TI  - IL-27 regulates IL-10 and IL-17 from CD4+ cells in nonhealing Leishmania major
      infection.
AB  - Control of infection caused by Leishmania major requires the development of IFN
      gamma+CD4+ lymphocytes for the induction of microbicidal activity in host
      macrophages. We recently reported on the inability of conventionally resistant
      C57BL/6 mice to successfully resolve infection by an isolate of L. major, despite
      a strong IFN-gamma response by the host. Susceptibility was caused by Ag-specific
      IL-10 from CD4+ cells that were also producing IFN-gamma. In the present studies,
      we have explored the role for IL-27 in the regulation of IL-10 from Th1 cells in
      leishmaniasis. Cytokine analysis of CD4+ cells in the lesions and draining lymph
      nodes of infected IL-27R-deficient (WSX-1(-/-)) mice revealed diminished IL-10
      from IFN-gamma+ CD4+ cells, which was accompanied by a reduction in total IFN
      gamma+CD4+ cells and an increase in IL-4. Despite the inhibition of IL-10 from
      CD4+ cells, no significant change in parasite numbers was observed, due both to
      the shift in the Th1/Th2 balance and to residual levels of IL-10. Strikingly,
      infected WSX-1(-/-) mice developed more severe lesions that were associated with
      the appearance of IL-17+ CD4+ cells, demonstrating a function for IL-27 in
      blocking the development of inappropriate Th17 cells during L. major infection.
      The results demonstrate the pleiotropic effects that IL-27 has on L. major-driven
      Th1, Th2, and Th17 development, and reinforce its function as a key regulatory
      cytokine that controls the balance between immunity and pathology.

PMID- 19748992
TI  - Portion size: a qualitative study of consumers' attitudes toward point-of
      purchase interventions aimed at portion size.
AB  - This qualitative study assessed consumers' opinions of food portion sizes and
      their attitudes toward portion-size interventions located in various point-of
      purchase settings targeting overweight and obese people. Eight semi-structured
      focus group discussions were conducted with 49 participants. Constructs from the
      diffusion of innovations theory were included in the interview guide. Each focus
      group was recorded and transcribed verbatim. Data were coded and analyzed with
      Atlas.ti 5.2 using the framework approach. Results showed that many participants
      thought that portion sizes of various products have increased during the past
      decades and are larger than acceptable. The majority also indicated that value
      for money is important when purchasing and that large portion sizes offer more
      value for money than small portion sizes. Furthermore, many experienced
      difficulties with self-regulating the consumption of large portion sizes. Among
      the portion-size interventions that were discussed, participants had most
      positive attitudes toward a larger availability of portion sizes and pricing
      strategies, followed by serving-size labeling. In general, reducing package
      serving sizes as an intervention strategy to control food intake met resistance.
      The study concludes that consumers consider interventions consisting of a larger
      variety of available portion sizes, pricing strategies and serving-size labeling
      as most acceptable to implement.

PMID- 19748993
TI  - Gene and protein responses of human monocytes to extracellular cysteine redox
      potential.
AB  - The redox potential of the major thiol/disulfide couple, cysteine (Cys) and its
      disulfide cystine (CySS), in plasma (E(h)Cys) is oxidized in association with
      oxidative stress, and oxidized E(h)Cys is associated with cardiovascular disease
      risk. In vitro exposure of monocytes to oxidized E(h)Cys increases expression of
      the proinflammatory cytokine, interleukin-1beta (IL-1beta), suggesting that
      E(h)Cys could be a mechanistic link between oxidative stress and chronic
      inflammation. Because cell membranes contain multiple Cys-rich proteins, which
      could be sensitive to E(h)Cys, we sought to determine whether E(h)Cys
      specifically affects proinflammatory signaling or has other effects on monocytes.
      We used microarray analysis and mass spectrometry-based proteomics to evaluate
      global changes in protein redox state, gene expression, and protein abundance in
      monocytes in response to E(h)Cys. Pathway analysis results revealed that in
      addition to IL-1beta-related pathways, components of stress/detoxification and
      cell death pathways were increased by oxidized E(h)Cys, while components of cell
      growth and proliferation pathways were increased by a reduced potential.
      Phenotypic studies confirmed that a cell stress response occurred with oxidized
      E(h) and that cell proliferation was stimulated with reduced E(h). Therefore,
      plasma E(h)Cys provides a control over monocyte phenotype, which could contribute
      to cardiovascular disease risk and provide a novel therapeutic target for disease
      prevention.

PMID- 19748994
TI  - Investigation of peptide reactivity of pro-hapten skin sensitizers using a
      peroxidase-peroxide oxidation system.
AB  - Skin protein reactivity is a well established key step in the development of skin
      sensitization. Understanding the relationship between a chemical's ability to
      react with or modify skin protein and skin sensitization has led to the
      development of the Direct Peptide Reactivity Assay (DPRA) in our laboratory. A
      current limitation of the DPRA is that it cannot readily measure the reactivity
      of pro-hapten chemical sensitizers. Pro-haptens are chemical sensitizers that are
      not directly reactive and must be bioactivated in vivo to form an electrophilic
      intermediate(s). Results from this work demonstrate the utility of using
      horseradish peroxidase and hydrogen peroxide (HRP/P) for assessing the skin
      sensitization potential of pro-haptens. In comparison with "direct" reactivity
      assessments without HRP/P, statistically significant increases in peptide
      depletion for all pro-haptens examined were observed following coincubation with
      HRP/P. Conversely, the percent peptide depletion for all pre-haptens was equally
      high (> 40% depletion) with and without HRP/P demonstrating an auto-oxidation
      pathway. In contrast, peptide depletion for all nonsensitizing chemicals examined
      was low with and without HRP/P. The optimal HRP/P concentrations, incubation time
      and optimal peptide:chemical ratio were determined using a sensitive and
      selective high-performance liquid chromatography tandem mass spectrometry
      detection method. Dithiothreitol was incorporated to reverse the dimerization of
      the thiol-containing cysteine peptide nucleophile. This preliminary work shows
      the potential to incorporate an enzyme-mediated activation step for pro-haptens
      into an in chemico skin sensitization assay that results in the detection of all
      types of sensitizers.

PMID- 19748995
TI  - Ligand activation of peroxisome proliferator-activated receptor-beta/delta and
      inhibition of cyclooxygenase-2 enhances inhibition of skin tumorigenesis.
AB  - Ligand activation of peroxisome proliferator-activated receptor (PPAR)-beta/delta
      and inhibition of cyclooxygenase-2 (COX-2) activity by nonsteroidal anti
      inflammatory drugs can attenuate skin tumorigenesis. There is also evidence that
      attenuation of skin tumorigenesis by inhibition of COX-2 activity occurs through
      PPARbeta/delta-independent mechanisms. The present study examined the hypothesis
      that combining ligand activation of PPARbeta/delta with inhibition of COX-2
      activity will cooperatively inhibit chemically induced skin tumor progression
      using both in vivo and ex vivo models. A two-stage chemical carcinogenesis
      bioassay was performed in wild-type and Pparbeta/delta-null mice. After 22 weeks,
      cohorts of both mouse lines were divided into four experimental groups: (1)
      control, (2) topical application of the PPARbeta/delta ligand GW0742, (3) dietary
      administration of the COX-2 inhibitor nimesulide, or (4) both GW0742 and
      nimesulide. Ligand activation of PPARbeta/delta did not influence skin tumor
      progression, while a modest decrease in skin tumor multiplicity was observed with
      dietary nimesulide. Interestingly, the combined treatment of GW0742 and
      nimesulide increased the efficacy of the decrease in papilloma multiplicity for 6
      weeks in wild-type mice, but this effect was not found at later time points and
      was not found in similarly treated Pparbeta/delta-null mice. Neoplastic
      keratinocyte lines cultured with GW0742 and nimesulide also exhibited enhanced
      inhibition of cell proliferation coincident with increased expression of Keratin
      messenger RNAs. Results from these studies support the hypothesis that combining
      ligand activation of PPARbeta/delta with inhibition of COX-2 activity can inhibit
      chemically induced skin tumor progression by modulating differentiation.

PMID- 19748996
TI  - Acute morphological and toxicological effects in a human bronchial coculture
      model after sulfur mustard exposure.
AB  - Sulfur mustard (SM) is a strong alkylating agent. Inhalation of SM causes acute
      lung injury accompanied by severe disruption of the airway barrier. In our study,
      we tested the acute effects after mustard exposure in an in vitro coculture
      bronchial model of the proximal barrier. To achieve this, we seeded normal human
      bronchial epithelial explant-outgrowth cells (HBEC) together with lung
      fibroblasts as a bilayer on filter plates and exposed the bronchial model after
      31 days of differentiation to various concentrations of SM (30, 100, 300, and 500
      microM). The HBEC formed confluent layers, expressing functional tight junctions
      as measured by transepithelial electrical resistance (TER). Mucus production and
      cilia formation reappeared in the coculture model. TER was measured after 2 and
      24 h following treatment. Depending on the different concentrations, TER
      decreased in the first 2 h up to 55% of the control at the highest concentration.
      After 24 h, TER seemed to recover because at concentrations up to 300 microM
      values were equal to the control. SM induced a widening of intercellular spaces
      and a loss in cell-matrix adhesion. Mucus production increased with the result
      that cilia ceased to beat. Changes in the proinflammatory cytokines interleukin
      (IL)-6 and IL-8 were also observed. Apoptotic markers such as cytochrome c, p53,
      Fas-associated protein with death domain, and procaspase-3 were significantly
      induced at concentrations of less than 100 microM. In summary, SM induces
      morphological and biochemical changes that reflect pathological effects of SM
      injury in vivo. It is hoped to use this coculture model to understand further the
      pathogenesis of SM-induced barrier injury and to search for novel approaches in
      SM therapy.

PMID- 19748997
TI  - A single exposure to particulate or gaseous air pollution increases the risk of
      aconitine-induced cardiac arrhythmia in hypertensive rats.
AB  - Epidemiological studies demonstrate an association between arrhythmias and air
      pollution. Aconitine-induced cardiac arrhythmia is widely used experimentally to
      examine factors that alter the risk of arrhythmogenesis. In this study, Wistar
      Kyoto (WKY) and spontaneously hypertensive (SH) rats acutely exposed to synthetic
      residual oil fly ash (s-ROFA) particles (450 mug/m(3)) were "challenged" with
      aconitine to examine whether a single exposure could predispose to
      arrhythmogenesis. Separately, SH rats were exposed to varied particulate matter
      (PM) concentrations (0.45, 1.0, or 3.5 mg/m(3) s-ROFA), or the irritant gas
      acrolein (3 ppm), to better assess the generalization of this challenge response.
      Rather than directly cause arrhythmias, we hypothesized that inhaled air
      pollutants sensitize the heart to subsequent dysrhythmic stimuli. Twenty-four
      hour postexposure, urethane-anesthetized rats were monitored for heart rate (HR),
      electrocardiogram, and blood pressure (BP). SH rats had higher baseline HR and BP
      and significantly longer PR intervals, QRS duration, QTc, and JTc than WKY rats.
      PM exposure caused a significant increase in the PR interval, QRS duration, and
      QTc in WKY rats but not in SH rats. Heart rate variability was significantly
      decreased in WKY rats after PM exposure but increased in SH rats. Cumulative dose
      of aconitine that triggered arrhythmias in air-exposed SH rats was lower than WKY
      rats and even lower for each strain postexposure. SH rats exposed to varied
      concentrations of PM or acrolein developed arrhythmia at significantly lower
      doses of aconitine than controls; however, there was no PM concentration
      dependent response. In conclusion, a single exposure to air pollution may
      increase the sensitivity of cardiac electrical conduction to disruption.
      Moreover, there seem to be host factors (e.g., cardiovascular disease) that
      increase vulnerability to triggered arrhythmias regardless of the pollutant or
      its concentration.

PMID- 19748998
TI  - Animal models of pulmonary arterial hypertension: the hope for etiological
      discovery and pharmacological cure.
AB  - At present, six groups of chronic pulmonary hypertension (PH) are described.
      Among these, group 1 (and 1') comprises a group of diverse diseases termed
      pulmonary arterial hypertension (PAH) that have several pathophysiological,
      histological, and prognostic features in common. PAH is a particularly severe and
      progressive form of PH that frequently leads to right heart failure and premature
      death. The diagnosis of PAH must include a series of defined clinical parameters,
      which extend beyond mere elevations in pulmonary arterial pressures and include
      precapillary PH, pulmonary hypertensive arteriopathy (usually with plexiform
      lesions), slow clinical onset (months or years), and a chronic time course
      (years) characterized by progressive deterioration. What appears to distinguish
      PAH from other forms of PH is the severity of the arteriopathy observed, the
      defining characteristic of which is "plexogenic arteriopathy." The pathogenesis
      of this arteriopathy remains unclear despite intense investigation in a variety
      of animal model systems. The most commonly used animal models ("classic" models)
      are rodents exposed to either hypoxia or monocrotaline. Newer models, which
      involve modification of classic approaches, have been developed that exhibit more
      severe PH and vascular lesions, which include neointimal proliferation and
      occlusion of small vessels. In addition, genetically manipulated mice have been
      generated that have provided insight into the role of specific molecules in the
      pulmonary hypertensive process. Unfortunately, at present, there is no perfect
      preclinical model that completely recapitulates human PAH. All models, however,
      have provided and will continue to provide invaluable insight into the numerous
      pathways that contribute to the development and maintenance of PH. Use of both
      classic and newly developed animal models will allow continued rigorous testing
      of new hypotheses regarding pathogenesis and treatment. This review highlights
      progress that has been made in animal modeling of this important human condition.

PMID- 19748999
TI  - Elastase- and LPS-exposed mice display altered responses to rhinovirus infection.
AB  - Viral infection is associated with approximately one-half of acute exacerbations
      of chronic obstructive pulmonary disease (COPD), which in turn, accelerate
      disease progression. In this study, we infected mice exposed to a combination of
      elastase and LPS, a constituent of cigarette smoke and a risk factor for
      development of COPD, with rhinovirus serotype 1B, and examined animals for viral
      persistence, airway resistance, lung volume, and cytokine responses. Mice exposed
      to elastase and LPS once a week for 4 wk showed features of COPD such as airway
      inflammation and obstruction, goblet cell metaplasia, reduced lung elastance,
      increased total lung volume, and increased alveolar chord length. In general,
      mice exposed to elastase or LPS alone showed intermediate effects. Compared with
      rhinovirus (RV)-infected PBS-exposed mice, RV-infected elastase/LPS-exposed mice
      showed persistence of viral RNA, airway hyperresponsiveness, increased lung
      volume, and sustained increases in expression of TNFalpha, IL-5, IL-13, and
      muc5AC (up to 14 days postinfection). Furthermore, virus-induced IFNs, interferon
      response factor-7, and IL-10 were deficient in elastase/LPS-treated mice. Mice
      exposed to LPS or elastase alone cleared virus similar to PBS-treated control
      mice. We conclude that limited exposure of mice to elastase/LPS produces a COPD
      like condition including increased persistence of RV, likely due to skewing of
      the immune response towards a Th2 phenotype. Similar mechanisms may be operative
      in COPD.

PMID- 19749000
TI  - Therapeutic effects of hypercapnia on chronic lung injury and vascular remodeling
      in neonatal rats.
AB  - Permissive hypercapnia, achieved using low tidal volume ventilation, has been an
      effective protective strategy in patients with acute respiratory distress
      syndrome. To date, no such protective effect has been demonstrated for the
      chronic neonatal lung injury, bronchopulmonary dysplasia. The objective of our
      study was to determine whether evolving chronic neonatal lung injury, using a rat
      model, is resistant to the beneficial effects of hypercapnia or simply requires a
      less conservative approach to hypercapnia than that applied clinically to date.
      Neonatal rats inhaled air or 60% O2 for 14 days with or without 5.5% CO2. Lung
      parenchymal neutrophil and macrophage numbers were significantly increased by
      hyperoxia alone, which was associated with interstitial thickening and reduced
      secondary crest formation. The phagocyte influx, interstitial thickening, and
      impaired alveolar formation were significantly attenuated by concurrent
      hypercapnia. Hyperoxic pups that received 5.5% CO2 had a significant increase in
      alveolar number relative to air-exposed pups. Increased tyrosine nitration, a
      footprint for peroxynitrite-mediated reactions, arteriolar medial wall
      thickening, and both reduced small peripheral pulmonary vessel number and VEGF
      and angiopoietin-1 (Ang-1) expression, which were observed with hyperoxia, was
      attenuated by concurrent hypercapnia. We conclude that evolving chronic neonatal
      lung injury in a rat model is responsive to the beneficial effects of
      hypercapnia. Inhaled 5.5% CO2 provided a significant degree of protection against
      parenchymal and vascular injury in an animal model of chronic neonatal lung
      injury likely due, at least in part, to its inhibition of a phagocyte influx.

PMID- 19749001
TI  - The biocompatibility of sulfobetaine engineered poly (ethylene terephthalate) by
      surface entrapment technique.
AB  - Sulfobetaine-modified poly(ethylene terephthalate) (PET) systems were created by
      physically entrapping the zwitterionic species on the PET surface. The presence
      of the sulfobetiane molecules on these surfaces were verified by ATR-FTIR and SEM
      EDAX analysis, while wettability of the films was investigated by water contact
      angle measurements. The blood compatibility of the modified films was evaluated
      by platelet adhesion in human platelet-rich plasma (PRP). The adhesion and
      inflammatory response of Mouse RAW 264.7 macrophage cells were studied. The
      surface induced cellular inflammatory response was determined by quantifying the
      expression levels of proinflammatory cytokines namely TNF-alpha and IL-1beta by
      measuring their mRNA profiles in the cells using real time polymerase chain
      reaction normalized to the housekeeping gene GAPDH. L-929 fibroblast cells were
      used to assess the propensity of the materials to support the fibroblast cell
      adhesion. A lower platelet adhesion and activation were observed on the
      sulfobetaine-modified PET film incubated in PRP after 2h when compared to
      control. The modified film reduced cellular adhesion events ( p<0.05) with
      respect to the base material, which could be linked to the reduced protein
      adsorption observed on this surface. The cellular inflammatory response was
      suppressed on sulfobetaine-modified substrate. Expression levels of pro
      inflammmatory cytokines (TNF-alpha and IL-1beta) was found to be upregulated on
      bare PET, while it was significantly lower on modified PET ( p<0.001). Thus the
      sulfobetaine entrapment process can be applied on PET in order to achieve low
      biointeractions and reduced inflammatory host response for various biomedical and
      biotechnological applications.

PMID- 19749002
TI  - Biomechanical and radiographic comparison of demineralized bone matrix, and a
      coralline hydroxyapatite in a rabbit spinal fusion model.
AB  - The use of bone grafts is an essential component in spinal fusion. Autologous
      bone has been shown to result in long-term stable arthrodesis between spinal
      motion segments. However, autograft can be associated with significant morbidity
      and a limited supply. Alternatives, such as allogeneic demineralized bone matrix
      (DBM), are a potential source and supplement to autograft bone. The current study
      compares the ability of a DBM product (BioSet RT) and a coralline hydroxyapatite
      (Pro Osteon 500R), for inducing spinal fusion in a rabbit model. BioSet RT, alone
      or in combination with autograft, and Pro Osteon 500R were implanted in the
      posterior lateral inter-transverse process region of the rabbit spine. The spines
      were evaluated at 18 weeks for fusion of the L4-L5 transverse processes using a
      total of 33 skeletally mature male rabbits; 4 naive animals were also included in
      the study. Samples were evaluated radiographically, histologically, by palpation,
      and through mechanical strength testing. Radiographical, histological, and
      palpation measurements demonstrated the ability of BioSet RT to induce new bone
      formation and bridging fusion comparable to autograft. This material performed
      well alone or in combination with autograft material. Despite significantly
      higher biomechanical testing results, minimal bone formation and fusion was
      recorded for the Pro Osteon 500R-treated group. This in vivo study demonstrates
      the ability of BioSet RT to induce new bone formation, and there was a clear
      relationship between bridging bone and mechanical strength.

PMID- 19749003
TI  - Once-daily evening dosing of mometasone furoate administered via a dry powder
      inhaler does not adversely affect the hypothalamic-pituitary-adrenal axis.
AB  - BACKGROUND: Inhaled corticosteroids can suppress the hypothalamic-pituitary
      adrenal (HPA) axis with long-term exposure. This study reports the effects of
      moderate-dose (400 microg) mometasone furoate administered via dry powder inhaler
      (MF-DPI) once daily in the evening on the HPA axis in adults with mild to
      moderate asthma. METHODS: In this randomized, investigator-blind, placebo
      controlled trial, nonsmoking adults aged 18 to 50 years with mild-to-moderate
      asthma received once-daily MF-DPI 400 microg (2 x 200 microg/inhalation;
      treatment A), MF-DPI 400 microg (1 x 400 microg/inhalation; treatment B), or
      placebo (two inhalations, treatment C), delivered at approximately 8:00 pm, for
      42 days. Primary end points were area under the serum cortisol concentration-vs
      time curve over 24 h (AUC(0-24)), 24-h urinary free cortisol (creatinine
      corrected) on day 42, maximum serum cortisol concentration (C(max)), time to
      C(max) (T(max)), and 8 :00 am serum cortisol concentration. This study was
      initiated April 16, 2001 and completed June 14, 2001. RESULTS: Serum cortisol
      AUC(0-24), C(max), and 24-h urinary free cortisol levels decreased with all
      treatments by day 42 with no significant differences between groups. For
      treatment B, the change in 8:00 am serum cortisol from baseline to day 42 was
      significantly less than placebo (P = .04), attributed to a large baseline
      difference between these treatments. A significant difference in T(max) change
      from baseline by day 42 for treatment B compared with the other treatments (P =
      .019) was also attributed to significant baseline differences between groups.
      Actual values at day 42 for T(max) and 8:00 am serum cortisol were not
      significantly different between treatment groups (P > or = .275). CONCLUSIONS:
      Once-evening moderate dosing (400 microg) MF-DPI does not suppress HPA axis
      function in adults with mild to moderate asthma.

PMID- 19749004
TI  - Neutrophils are the predominant infected phagocytic cells in the airways of
      patients with active pulmonary TB.
AB  - BACKGROUND: The exact role of neutrophils in the pathogenesis of TB is poorly
      understood. Recent evidence suggests that neutrophils are not simply scavenging
      phagocytes in Mycobacterium tuberculosis (Mtb) infection. METHODS: Three
      different types of clinical specimens from patients with active pulmonary TB who
      underwent lung surgery were examined: sputum, BAL fluid, and cavity contents.
      Differential cell separation and quantification were performed for intracellular
      and extracellular bacteria, and bacterial length was measured using microscopy.
      RESULTS: Neutrophils were more abundant than macrophages in sputum (86.6% +/-
      2.2% vs 8.4% +/- 1.3%) and in BAL fluid (78.8% +/- 5.8% vs 11.8% +/- 4.1%).
      Inside the cavity, lymphocytes (41.3% +/- 11.2%) were the most abundant cell
      type, followed by neutrophils (38.8% +/- 9.4%) and macrophages (19.5% +/- 7.5%).
      More intracellular bacilli were found in neutrophils than macrophages in sputum
      (67.6% +/- 5.6% vs 25.2% +/- 6.5%), in BAL fluid (65.1% +/- 14.4% vs 28.3% +/-
      11.6%), and in cavities (61.8% +/- 13.3% vs 23.9% +/- 9.3%). The lengths of Mtb
      were shortest in cavities (1.9+/- 0.1 microm), followed by in sputum (2.9 +/- 0.1
      microm) and in BAL fluid (3.6 +/- 0.2 microm). CONCLUSIONS: Our results show that
      neutrophils are the predominant cell types infected with Mtb in patients with TB
      and that these intracellular bacteria appear to replicate rapidly. These results
      are consistent with a role for neutrophils in providing a permissive site for a
      final burst of active replication of the bacilli prior to transmission.

PMID- 19749005
TI  - Incidence, prevalence, and clinical course of idiopathic pulmonary fibrosis: a
      population-based study.
AB  - BACKGROUND: Limited data exist regarding the population-based epidemiology of
      idiopathic pulmonary fibrosis (IPF). The objective of the study was to describe
      the trends in the incidence, prevalence, and clinical course of IPF in the
      community. METHODS: We conducted a population-based study of adult patients with
      IPF in Olmsted County, Minnesota, from 1997 to 2005. Two methods were used to
      identify IPF cases, as defined by the 2002 American Thoracic Society/European
      Respiratory Society consensus statement: (1) usual interstitial pneumonia (UIP)
      on a surgical lung biopsy specimen or a definite UIP pattern on a high-resolution
      CT image (narrow criteria) and (2) UIP on a surgical lung biopsy specimen or a
      definite or possible UIP pattern on CT image (broad criteria). RESULTS: Of 596
      patients screened for the possibility of pulmonary disease or pulmonary fibrosis
      over 9 years of follow-up, 47 cases had IPF. Of these, 24 met the narrow
      criteria. The age- and sex-adjusted incidence was 8.8/100,000 and 17.4/100,000
      person-years, for narrow and broad criteria, respectively. The age-adjusted
      incidence was higher in men than in women, and among patients aged 70-79 years.
      During the study period, the incidence of IPF decreased (P < .001). On December
      31, 2005, the age- and sex-adjusted prevalence was 27.9/100,000 and 63/100,000
      persons by narrow and broad criteria, respectively. Thirty-seven patients
      experienced a total of 53 respiratory exacerbations (26 IPF related, 27 non-IPF
      related), and 34 (72%) patients died. The primary cause of death was IPF related
      in 16 (47%) patients. Median survival for narrow-criteria and broad-criteria
      incidence cases was 3.5 and 4.4 years, respectively. CONCLUSIONS: The incidence
      of IPF in Olmsted County decreased over the study period. Nonprimary IPF
      respiratory exacerbations are as frequent as primary IPF respiratory
      exacerbations and an important cause of death.

PMID- 19749006
TI  - Noninvasive ventilation reduces intubation in chest trauma-related hypoxemia: a
      randomized clinical trial.
AB  - BACKGROUND: Guidelines for noninvasive mechanical ventilation (NIMV) recommend
      continuous positive airway pressure in patients with thoracic trauma who remain
      hypoxic despite regional anesthesia. This recommendation is rated only by level C
      evidence because randomized controlled trials in this specific population are
      lacking. Our aim was to determine whether NIMV reduces intubation in severe
      trauma-related hypoxemia. METHODS: This was a single-center randomized clinical
      trial in a nine-bed ICU of a level I trauma hospital. Inclusion criteria were
      patients with Pao(2)/Fio(2)<200 for >8 h while receiving oxygen by high-flow mask
      within the first 48 h after thoracic trauma. Patients were randomized to remain
      on high-flow oxygen mask or to receive NIMV. The interface was selected based on
      the associated injuries. Thoracic anesthesia was universally supplied unless
      contraindicated. The primary end point was intubation; secondary end points
      included length of hospital stay and survival. Statistical analysis was based on
      multivariate analysis. RESULTS: After 25 patients were enrolled in each group,
      the trial was prematurely stopped for efficacy because the intubation rate was
      much higher in controls than in NIMV patients (10 [40%] vs 3 [12%], P = .02).
      Multivariate analysis adjusted for age, gender, chronic heart failure, and Acute
      Physiology and Chronic Health Evaluation II at admission revealed NIMV as the
      only variable independently related to intubation (odds ratio, 0.12; 95% CI, 0.02
      0.61; P = .01). Length of hospital stay was shorter in NIMV patients (14 vs 21
      days P = .001), but no differences were observed in survival or other secondary
      end points. CONCLUSION: NIMV reduced intubation compared with oxygen therapy in
      severe thoracic trauma-related hypoxemia.

PMID- 19749007
TI  - Survival following sublobar resection for early-stage non-small cell lung cancer
      with or without adjuvant external beam radiation therapy: a population-based
      study.
AB  - BACKGROUND: Patients undergoing sublobar resection for early-stage non-small cell
      lung cancer may receive adjuvant radiation therapy in an effort to improve
      outcomes despite limited data regarding its efficacy. METHODS: Using the
      Surveillance, Epidemiology, and End-Results (SEER) registry we identified
      patients diagnosed with stage I non-small cell lung cancer between 1988 and 2003
      who were definitively treated with sublobar surgical resection with or without
      adjuvant external beam radiation therapy. Kaplan-Meier, Cox regression, and
      propensity-score-matched survival analyses were performed to evaluate the effect
      of adjuvant external beam radiation therapy on survival. RESULTS: A total of
      5,908 eligible cases were identified: 493 received external beam radiation
      therapy and 5,415 received no additional local-regional treatment. The use of
      external beam radiation therapy was associated with significantly worse median
      overall and disease-specific survival compared with no additional local-regional
      therapy: 31 and 45 months vs 51 and 98 months, respectively (P < .001). On
      multivariate analysis, the most significant predictor of death was the use of
      adjuvant radiation therapy (hazard ratio 1.505; 95% CI, 1.318-1.717; P < .001).
      The survival detriment associated with external beam radiation therapy remained
      after propensity-score-matched analysis. CONCLUSIONS: The use of adjuvant
      external beam radiation therapy is associated with a significant decrease in
      overall and disease-specific survival for patients with T1-2N0M0 non-small cell
      lung cancer treated with sublobar resection. Although this finding may be related
      to covariables not reported in SEER, such as margin status, chemotherapy use,
      radiation dose, and portal, alternative radiation treatment strategies should be
      explored.

PMID- 19749008
TI  - Increased relative mortality in women with severe oxygen-dependent COPD.
AB  - BACKGROUND: Although the incidence of COPD is rapidly increasing in women,
      knowledge is lacking concerning differences in relative mortality and causes of
      death in women compared with men. We aimed to analyze differences in relative
      mortality and cause-specific mortality between men and women on long-term oxygen
      therapy (LTOT) for COPD. METHODS: Patients starting LTOT for COPD in Sweden
      between January 1, 1987, and December 31, 2004, were prospectively followed until
      termination of LTOT or through December 31, 2004. Causes of death according to
      the Swedish National Causes of Death Register were compared between the study
      group and the general Swedish population matched for age and sex, with the
      relative mortality expressed as standardized mortality rates (SMRs). RESULTS: A
      total of 7,646 patients, 4,033 women and 3,613 men, were followed for a median of
      1.7 years (range 0-18.0). No patient was lost to follow-up. A total of 5,448
      patients, 2,745 women and 2,703 men, died. Women had a higher SMR than men:
      overall mortality, SMR 12.0 (95%, 11.6-12.5) vs 7.4 (95% CI, 7.1-7.6); for
      respiratory disease, SMR 127.9 (95% CI, 122.4-133.6) vs 66.0 (95% CI, 63.1-69.0);
      cancer, SMR 3.5 (95% CI, 3.0-3.9) vs 2.2 (95% CI, 1.9-2.5); and cardiovascular
      disease, SMR 3.7 (95% CI, 3.3-4.1) vs 2.5 (95% CI, 2.3-2.7), respectively.
      CONCLUSIONS: In severe COPD treated with long-term oxygen, women have higher
      relative mortality than men both overall and for respiratory disease, as well as
      for cardiovascular disease and cancer.

PMID- 19749009
TI  - Multiplex molecular detection of respiratory pathogens in children with asthma
      exacerbation.
AB  - BACKGROUND: Up to 80% of asthma exacerbations in white children are associated
      with viral upper respiratory infections. The relative importance of different
      respiratory pathogens and relevant microbiological data in Asian children are
      unclear. This study elucidated the epidemiology of respiratory infections in Hong
      Kong children with asthma exacerbation. METHODS: A total of 209 children aged 3
      18 years with asthma exacerbations and 77 controls with stable asthma were
      recruited. The severity of asthma exacerbations was assessed according to Global
      Initiative for Asthma guideline, and subjects aged 6 years or older performed
      exhaled nitric oxide and spirometric measurements. Nested multiplex polymerase
      chain reaction was used to detect 20 different respiratory pathogens. RESULTS:
      Respiratory pathogens were detected in 105 (51.0%) subjects. The presence of any
      respiratory pathogen was associated with asthma exacerbation (odds ratio [OR],
      2.77; 95% CI, 1.51-5.11; P < .001). Specifically, human rhinovirus (HRV)
      infection was more common among children with asthma exacerbation (OR, 2.38; 95%
      CI, 1.09-5.32; P = .018). All other pathogens or coinfections were not associated
      with asthmatic attacks. None of these respiratory infections was associated with
      the severity of asthma exacerbation (P > .15 for all). During peak HRV season in
      the winter of 2007 to 2008, this virus was detected in 46.4% of children with
      asthma exacerbations. CONCLUSIONS: Respiratory viral infections are commonly
      found in children with asthma exacerbation, with HRV being the most important
      pathogen in our patients. Respiratory viral infection is a triggering factor for
      asthma exacerbation but does not correlate with its severity.

PMID- 19749010
TI  - Oestrogen receptor 1 mRNA is a prognostic factor in ovarian cancer patients
      treated with neo-adjuvant chemotherapy: determination by array and kinetic PCR in
      fresh tissue biopsies.
AB  - Oestrogen receptors (ESRs) regulate the growth and differentiation of normal
      ovarian epithelia. However, to date their role as biomarkers in the clinical
      setting of ovarian cancer remains unclear. In view of potential endocrine
      treatment options, we tested the role of ESR1 mRNA expression in ovarian cancer
      in the context of a neo-adjuvant chemotherapy trial. Study participants had
      epithelial ovarian or peritoneal carcinoma unsuitable for optimal upfront surgery
      and were treated with neo-adjuvant platinum-based chemotherapy before surgery.
      RNA was isolated from frozen tumour biopsies before treatment. RNA expression of
      ESR1 was determined by microarray and reverse transcriptase kinetic PCR
      technologies. The prognostic value of ESR1 was tested using univariate and
      multivariate Cox proportional hazards models, Kaplan-Meier survival statistics
      and the log-rank test. ESR1 positively correlates with proliferation markers and
      histopathological grading. ESR1 was a significant predictor of survival as a
      continuous variable in the univariate Cox regression analysis. In multivariate
      analysis, elevated baseline ESR1 mRNA levels predicted prolonged progression-free
      survival (P=0.041) and overall survival (P=0.01) after neo-adjuvant chemotherapy,
      independently of pathological grade and age. We conclude that pretreatment ESR1
      mRNA is associated with tumour growth and is a strong prognostic factor in
      ovarian cancer, independent of the strongest clinical parameters used in clinical
      routine. We suggest that ESR1 mRNA status should be considered in order to
      minimize possible confounding effects in ovarian cancer clinical trials, and that
      early treatment with anti-hormonal agents based on reliable hormone receptor
      status determination is worth investigating.

PMID- 19749011
TI  - Child immunization coverage in urban slums of Bangladesh: impact of an
      intervention package.
AB  - The study assessed the impact of an EPI (Expanded Programme on Immunization)
      intervention package, implemented within the existing service-delivery system, to
      improve the child immunization coverage in urban slums of Dhaka, Bangladesh. This
      intervention trial used a pre- and post-test design. An intervention package was
      tested from September 2006 to August 2007 in two urban slums. The intervention
      package included: (a) an extended EPI service schedule; (b) training for service
      providers on valid doses and management of side-effects; (c) a screening tool to
      identify immunization needs among clinic attendants; and (d) an EPI support group
      for social mobilization. Data were obtained from random sample surveys, service
      statistics and qualitative interviews. Analysis of quantitative data was based on
      a 'before and after' assessment of selected immunization-coverage indicators.
      Qualitative data were analysed using content analysis. Ninety-nine per cent of
      the children were fully immunized after implementation of the interventions
      compared with only 43% before implementation. Antigen-wise coverage after
      implementation was also significantly higher compared with before implementation.
      Only 1% drop-out was observed after implementation of the interventions while it
      was 33% before implementation. At baseline, a significantly higher proportion of
      children of non-working mothers (75%) were fully immunized compared with children
      of working mothers (14%). Although the proportion of fully immunized children of
      both non-working and working mothers was significantly higher at endline, fully
      immunized children of working mothers dramatically improved at endline (99%)
      compared with baseline (14%). The findings suggest the effectiveness of a
      'package of interventions' in improving child immunization coverage in urban
      slums. However, further research is needed to fully assess the effectiveness of
      the package, to assess the individual components in order to identify those that
      make the biggest contribution to coverage, and to assess the sustainability of
      this package within the existing service delivery system, particularly on a wider
      scale.

PMID- 19749012
TI  - Effect of extended withdrawal of zilpaterol hydrochloride on performance and
      carcass traits in finishing beef steers.
AB  - The objective was to evaluate the effects of an extended withdrawal period after
      feeding the beta-adrenergic agonist zilpaterol hydrochloride (ZH) for 20 d at the
      end of the feeding period. Three hundred eighty-four crossbred beef steers were
      blocked by BW and randomly allocated into 64 pens (6 steers/pen). Pens were
      assigned to treatments in a 2 x 4 factorial arrangement in a randomized complete
      block design. Main effects were the addition of 0 (control) or 8.3 mg/kg of ZH
      (DM basis) to the finishing diet for 20 d before estimated average slaughter date
      and paired withdrawal periods of 3, 10, 17, or 24 d before slaughter. Individual
      BW were measured initially, 1 d before ZH feeding, and 1 d before slaughter. The
      ZH feeding period was initiated so that control cattle in the 3-d withdrawal
      group would be expected to average 65% USDA Choice Quality grade and have 1.27 cm
      of 12th-rib fat based on visual appraisal. Carcass data were collected at
      slaughter. For the 3-d withdrawal steers, 2 steers from each pen were selected to
      determine visceral organ and total offal mass at slaughter. The ZH x withdrawal
      day interaction was not significant (P > 0.10) for the majority of variables.
      There was no difference (P > or = 0.12) due to ZH feeding for final BW, carcass
      adjusted final BW, or ADG. However, DMI was decreased (P = 0.02) and G:F
      increased (P = 0.01) in steers fed ZH vs. control steers. As day after withdrawal
      of ZH increased, there was a linear increase (P < 0.001) in final BW and carcass
      adjusted final BW, but a linear decrease (P < 0.001) in ADG over the finishing
      period and over the ZH plus withdrawal period. Overall, HCW was 380 and 369 kg (P
      < 0.001) for ZH and control steers, respectively. However, the difference between
      ZH and control was 14, 17, 5, and 6 kg with 3, 10, 17, and 24 d withdrawal,
      respectively (ZH x withdrawal day, P = 0.09). Feeding ZH increased dressing
      percentage (65.8 vs. 64.6%; P < 0.001) and LM area (94.8 vs. 89.7 cm(2); P <
      0.001), and decreased calculated yield grade (2.69 vs. 2.91; P = 0.03) and
      percentage of cattle grading USDA Choice (31.1 vs. 42.3%; P = 0.03) compared with
      controls. Small intestinal mass (g/kg of empty BW) was greater (P = 0.03) for
      steers fed ZH compared with controls. There were no other differences (P > or =
      0.11) in mass of body components, expressed in kilograms or as a fraction of
      empty BW. In this experiment, improvements in animal performance and HCW due to
      feeding ZH were generally maintained when withdrawal was extended through 10 d.

PMID- 19749013
TI  - Fine mapping of quantitative trait loci for meat color on Sus scrofa chromosome
      6: analysis of the swine NUDT7 gene.
AB  - In the livestock industry, meat color has become important because consumer
      acceptance is subject to the appearance of the product in the marketplace. Our
      previous analyses of a whole genome QTL scan for various meat qualities using 2
      F(2) families from Japanese wild boar (known as a red meat) x Large White and
      from Duroc x Chinese Jinhua suggested that a meat color (heme content) QTL is
      located on SSC6. The objective of this study was to fine-map this SSC6 meat color
      QTL and subsequently investigate positional candidate genes for polymorphisms
      that may cause changes in meat color. Therefore, we conducted interval mapping on
      SSC6 using an additional 9 gene markers through combined analyses of the 2 F(2)
      families of Japanese wild boar x Large White (353 progeny) and Duroc x Chinese
      Jinhua (204 progeny). Comparative analysis with humans, mice, and cattle
      suggested that there were 10 functional genes in the region. Among these genes,
      we suggested that a novel pig gene encoding a nudix (nucleoside diphosphate
      linked moiety X)-type motif 7 (NUDT7, a member of the nudix hydrolases) is a
      strong candidate for the QTL because the mouse Nudt7 is reported to hydrolyze
      succinyl-CoA, a substrate of the reaction limiting the rate of heme biosynthesis.
      We therefore determined the pig NUDT7 gene sequence including the 5' promoter
      region and explored genetic polymorphisms between Japanese wild boar and Large
      White. We identified 116 polymorphisms within the NUDT7 CDS or in the 5' region.
      None of the AA substitutions were associated with the meat color QTL; however, 3
      polymorphisms were found in putative transcription factor recognition sites. We
      then investigated the differential expression of NUDT7 in Japanese wild boar and
      Large White by allele-specific quantitative real-time PCR. The expression level
      of the Large White type allele was greater than that of the Japanese wild-boar
      type allele. Consequently, we speculated that the difference in meat color
      between Japanese wild boar and Large White is caused partly by differential
      expression of this candidate gene. Upregulation of NUDT7 expression in muscle may
      reduce succinyl-CoA content and thus reduce the level of heme biosynthesis.

PMID- 19749014
TI  - Fall growth, nutritive value, and estimation of total digestible nutrients for
      cereal-grain forages in the north-central United States.
AB  - Throughout the Southern Great Plains, wheat is managed frequently as a dual
      purpose crop, but this production paradigm is not necessarily applicable
      throughout other regions of the United States, and a wider array of management
      options can be considered for forage-only uses of cereal grains. Our objectives
      were to assess the fall-growth potential of wheat (Triticum aestivum L.),
      triticale (X Triticosecale Wittmack), and oat (Avena sativa L.) cultivars in
      Wisconsin, and then to further evaluate and compare the fiber composition and TDN
      of these fall-grown forages. For 2006, yields of DM for all cultivars increased
      quadratically (P < or = 0.048) over fall harvest dates, reaching a maximum of
      3,967 kg/ha for Ogle oat. All oat cultivars exhibited stem elongation and also
      displayed a collective 2 to 1 yield advantage over vegetative wheat cultivars on
      the final (October 30) harvest date. Growing conditions were more favorable
      during 2007, and yields were improved for all cultivars. Yields of DM for all
      cultivars increased quadratically (P < or = 0.021) across harvest dates, and oat
      cultivars maintained the identical 2 to 1 yield advantage over wheat cultivars
      (6,275 vs. 3,203 kg/ha) that was observed for 2006. Triticale exhibited yields
      intermediate between oat and wheat during both years. Concentrations of NDF
      increased quadratically (P < or = 0.012) across harvest dates for all cultivars
      during both years of the experiment; however, these increases occurred primarily
      between mid September and early October with limited responses thereafter. Oat
      and triticale cultivars had greater (P < 0.001) concentrations of NDF than wheat
      cultivars on 5 of 6 harvest dates throughout the experiment. Estimates of TDN
      exhibited various polynomial responses to harvest date during 2006, but the
      magnitude of these changes was relatively small. During 2007, TDN declined
      linearly (P < or = 0.038) for grain-type oat, but no relationship with harvest
      date was observed for other cultivars (P > or = 0.072), including forage-type
      oat. Although TDN estimates generally were relatively static across harvest
      dates, the concentrations of truly digestible components constituting the total
      TDN pool were quite fluid. Generally, reductions of truly digestible CP were
      offset by increases in truly digestible nonfiber carbohydrate, truly digestible
      fiber, or both. The relatively stable energy densities for cereal-grain cultivars
      observed across harvest dates suggest that a broad window of opportunity exists
      for usage, including a single harvest as silage.

PMID- 19749015
TI  - Genetic relationships among calving ease, gestation length, and calf survival to
      weaning in the Asturiana de los Valles beef cattle breed.
AB  - The aim of this paper was to estimate the genetic relationships among calving
      ease (CE), calf survival (CS), and gestation length (GL) to assess the
      possibility of including this information in beef cattle breeding programs. A
      total of 35,395 field records were available for CE, 30,684 for GL, and 36,132
      for CS from the Asturiana de los Valles beef cattle breed. The 3 traits were
      analyzed as traits of the calf fitting a multivariate linear mixed model.
      Estimates of heritability (+/-SE) for the direct genetic effects (CEd, GLd, and
      CSd) were 0.325 +/- 0.022, 0.331 +/- 0.026, and 0.226 +/- 0.018, respectively,
      whereas the estimates for maternal genetic effects (CEm, GLm, and CSm) were 0.066
      +/- 0.018, 0.066 +/- 0.017, and 0.034 +/- 0.011. The estimates for the ratio of
      permanent environmental variance to phenotypic variance were CEc 0.090 +/- 0.011,
      GLc 0.066 +/- 0.011, and CSc 0.024 +/- 0.007. Genetic correlations between
      direct, maternal genetic, or permanent environmental effects involving CE and GL
      were, in general, positive and moderate, whereas those involving CE and CS were
      high. All were significant except for the pair CEm-GLm (0.277 +/- 0.172).
      Correlations between GL and CS were nonsignificant. Genetic correlations for CEd
      CEm, GLd-GLm, and CSd-CSm were negative and high, ranging from -0.461 +/- 0.120
      for GLd-GLm to -0.821 +/- 0.145 for CSd-CSm. The genetic correlations for CEd-CSm
      and for CSd-CEm were negative, significant, and high, whereas that for GLd-CEm
      was moderate (-0.323 +/- 0.124) and that for GLd-CSm was nonsignificant. The
      genetic correlations for GLm with the direct effects of the other traits were non
      significant. Strong selection for CE will result in a significant correlated
      response in CS. Therefore, CE can be considered an early indicator of CS
      performance. The benefit of using GL as a correlated trait in a genetic
      evaluation with CE and CS seems limited.

PMID- 19749016
TI  - Association analyses of candidate single nucleotide polymorphisms on reproductive
      traits in swine.
AB  - The ability to identify young females with superior reproduction would have a
      large economic impact on commercial swine production. Previous studies have
      discovered SNP associated with economically important traits such as litter size,
      growth rate, and feed intake. The objective of this study was to test for
      association of candidate SNP with sow prolificacy reproductive traits in gilts of
      a Landrace-Duroc-Yorkshire composite population. Association analyses regressed
      additive (A), dominant (D), and imprinting (I) SNP effects on each trait with an
      animal model. A carnitine palmitoyltransferase 1A SNP and a glycogen synthase 1
      SNP were associated with age at puberty (AP; D = 10 d; P = 0. 0037 and A = 3.8 d;
      P = 0.0078, respectively). Four IGF2 SNP were associated with AP as well, having
      additive or dominant effects (3.2 to 5.8 d; P < or = 0.0052). Two mannosidase 2B2
      SNP and 2 prolactin receptor (PRLR) SNP were also associated with AP. Solute
      carrier 22, subfamily member 5 SNP was weakly associated with AP (D = 3.9 d; P <
      0.10). Polymorphisms within glycogen synthase 1 and protein kinase AMP-activated,
      gamma 3 noncatalytic subunit had associations with ovulation rate. Estrogen
      receptor (ESR) 1, ESR2, PPAR gamma coactivator 1, and IGFBP3 SNP were
      significantly associated with weaning-to-estrus interval. Two PRLR SNP were
      associated with total number of piglets born (A = 0.57 piglets; P = 0.0095 and D
      = 0.61 piglets; P = 0.0016, respectively). A SNP within PRLR was also associated
      with number of piglets born alive (D = 0.61; P = 0.0016). The PPAR gamma
      coactivator 1 SNP was associated with total number of piglets born (D = 0.38
      piglets; P = 0.0391) and number of piglets born alive (D = 0.53 piglets; P =
      0.0032). The SNP within ESR1 (A = 0.65 piglets; P = 0.0950), ESR2 (A = -0.33
      piglets; P = 0.0176), IGF2 SNP (A = -0.26 piglets; P = 0.0032), and IGFBP3 SNP (D
      = 0.35 piglets; P = 0.0683) were associated with number of piglets born dead. A
      leptin SNP was associated with mummified fetuses (D = 0.09 piglets; P = 0.0978).
      Many of the SNP analyzed in this study are from genes involved in regulation of
      metabolism, suggesting that there is an important link between physiological
      events associated with reproduction and energy utilization. Furthermore, these
      production and growth trait SNP may serve to assist in selection of young females
      for superior reproductive performance.

PMID- 19749017
TI  - Estimation of genetic and crossbreeding parameters for preweaning traits in
      German Angus and Simmental beef cattle and the reciprocal crosses.
AB  - Data from pure breeds, as well as reciprocal crosses of German Angus (GA) and
      Simmental (SIM) beef cattle, were used to estimate genetic parameters and to
      evaluate the suitability for crossbreeding in terms of increasing productivity.
      Traits of interest were calving difficulty, birth weight (BWT), weaning weight
      (WWT), and ADG from birth to weaning. Data were collected over a period of 7 yr
      from 1997 and 1998 until 2003 and 2004, whereas crossbreeding was carried out in
      2002 and 2003, and 2003 and 2004 only. Variance components and differences
      between breeds, individual heterosis, and maternal breed effects were analyzed
      based on 1,441 purebred and 329 crossbred records for BWT and 1,319 purebred and
      316 crossbred records for WWT and ADG, respectively. Mean calving difficulty
      scores were greater in SIM than in GA (P < 0.001). For BWT, WWT, and ADG both
      reciprocal crosses fell between the purebreds, and for all 3 traits SIM showed
      greater average values compared with GA. The estimated heritabilities were 0.23
      for BWT and 0.12 for WWT. Values for the maternal effect and the correlation
      between additive and maternal effect were 0.18 for BWT, 0.08 for WWT, 0.32 for
      BWT, and 0.50 for WWT, respectively. Individual heterosis was only significant
      for BWT (3.7%; P < 0.01). Superior mothering ability of SIM was implicated by
      greater WWT and ADG of SIM as dam against the reciprocal cross (P < 0.001). The
      results provide information about the extent of individual heterosis and maternal
      breed effects.

PMID- 19749018
TI  - Effects of dietary protein level and amino acid supplementation on performance of
      mixed-parity lactating sows in a tropical humid climate.
AB  - Eighty-six mixed-parity Large White sows were used to determine the effect of
      diets with reduced CP content or supplemented with essential AA on 28-d lactation
      performance under humid tropical climatic conditions. This experiment was
      conducted in Guadeloupe (West French Indies, latitude 16 degrees N, longitude 61
      degrees W) between February 2007 and January 2008. Two seasons were distinguished
      a posteriori from climatic measurement variables continuously recorded in the
      farrowing room. The average minimum and maximum ambient temperatures and average
      daily relative humidity for the warm season were 20.5 and 28.2 degrees C, and
      93.8%, respectively. The corresponding values for the hot season were 22.7 and
      29.4 degrees C, and 93.7%, respectively. The dietary experimental treatments were
      a normal protein diet (NP), a low protein diet (LP), and a NP diet (NP+)
      supplemented with essential AA. The NP and LP diets supplied the same levels of
      standardized digestible Lys (i.e., 0.80 g/MJ of NE), and the NP+ diet supplied
      0.95 g/MJ of NE. No interaction between season and diet composition was noted on
      any response variable evaluated. The ADFI was decreased (P < 0.05) in the hot
      season (i.e., 3.69 vs. 4.72 kg) and therefore decreased by 500 g per degrees C
      increase of ambient temperature under high relative humidity conditions. The ADFI
      tended to be greater with the LP and NP+ diets when compared with the NP
      treatment (i.e., +10%, P = 0.08). Litter BW gain and mean BW of piglets at
      weaning were greater (P < 0.05) during the warm season than during the hot season
      (2.3 vs. 1.8 kg/d and 7.5 vs. 7.1 kg, respectively). Milk production and
      composition were not affected by dietary treatments but were affected by season
      (8.1 vs. 6.8 kg/d, for warm and hot seasons, respectively; P < 0.01). The sows
      fed LP and NP+ diets tended to have decreased backfat thickness losses (3.3 and
      3.8 mm, respectively; P > 0.08). In conclusion, the hot season in humid tropical
      climates, which combines high levels of temperature and humidity, has a
      pronounced negative impact on performance of lactating sows. Diets with low CP
      content or supplemented with essential AA can attenuate the effects of hot and
      humid season by increasing ADFI in lactating sows.

PMID- 19749019
TI  - Performance, residual feed intake, digestibility, carcass traits, and
      profitability of Angus-Hereford steers housed in individual or group pens.
AB  - Even though the concept of residual feed intake (RFI) is well accepted, several
      questions remain regarding other traits that may be associated with selection for
      decreased RFI. These include DM digestibility, carcass composition,
      profitability, and performance. The objective of this study was to investigate
      the difference in those traits between low- and high-RFI cattle. Sixty Angus x
      Hereford crossbred steers (296 kg of initial BW) were fed a corn-based finishing
      ration (1.68 Mcal of NE(m)/kg, 13% CP on a DM basis) during 2 periods of 60 d
      each. For both phases, the regression equation fitted without the intercept (not
      statistically significant) was DMI (kg/d) = 0.0701 x BW(0.75) + 2.714 x ADG, r(2)
      = 0.42. The 15 greatest and least RFI steers were classed as high and low RFI
      groups. There were no differences between low and high RFI groups for days on
      feed (162 vs. 168 d), slaughter weight (503 vs. 511 kg), HCW (317 vs. 315 kg), LM
      area (76.5 vs. 77.1 cm(2)), backfat (1.23 vs. 1.27 cm), KPH (3.1 vs. 3.7%),
      quality grade (average Choice for both groups), or carcass fat (32.4 vs. 33.1%).
      Visceral organ masses and abdominal fat were similar for low and high RFI groups
      (32.25 vs. 31.24 kg and 37.48 vs. 36.95 kg, respectively). These results do not
      support the existence of major differences in composition and organ mass between
      low and high RFI steers at slaughter. The RFI grouping had a significant effect
      on DMI, G:F, and RFI values. Stepwise regression showed that G:F alone or DMI and
      ADG together explained 98.5% of the variance in cost of BW gain, whereas RFI
      alone explained only 18%. We conclude that RFI is less useful than G:F as an
      indicator of feedlot efficiency and profitability.

PMID- 19749020
TI  - Comparative effects of virginiamycin supplementation on characteristics of growth
      performance, dietary energetics, and digestion of calf-fed Holstein steers.
AB  - Two trials were conducted to evaluate the influence of virginiamycin
      supplementation on growth performance and digestive function. In trial 1, 144
      Holstein steer calves (119 kg of initial BW) were used in a 340-d trial.
      Treatments were (DM basis) 1) control (no antibiotic); 2) 16 mg/kg of
      virginiamycin; 3) 22.5 mg/kg of virginiamycin; and 4) 28 mg/kg of monensin.
      Calves received a steam-flaked corn-based growing diet for the first 112 d and
      thereafter were fed a finishing diet from d 112 until slaughter. Steers were
      divided into 2 BW groups (lighter-half and heavier-half), and assigned within
      groups to 24 pens (6 steers/pen). Virginiamycin did not affect (P > 0.20) ADG,
      but increased 340-d G:F (linear; P = 0.02) and dietary NE (linear; P = 0.04).
      Improvements in dietary NE were most pronounced during the final 116 d of the
      feeding period (linear; P = 0.04) that comprised the hot summer months (June
      through September). Monensin did not affect (P > 0.20) growth performance or
      dietary NE. Although average initial BW of the lighter-half and heavier-half BW
      groups differed by only 4 kg, the heavier BW group had greater HCW (13 kg, P =
      0.02), LM area (5.4%, P = 0.01), ADG (4.3%, P = 0.02), G:F (2.3%, P = 0.08), and
      dietary NE (3.2%. P = 0.01) than the lighter BW group. In trial 2, 4 Holstein
      steers (269 +/- 3.5 kg) with cannulas in the rumen and proximal duodenum were
      used in a 4 x 4 Latin square design to evaluate treatment effects on digestion.
      Virginiamycin did not affect (P > 0.20) ruminal digestion of OM, NDF, starch, and
      N, and microbial efficiency, but tended to linearly increase (P = 0.09) ruminal N
      efficiency (nonammonia N flow to the small intestine/N intake). Likewise,
      virginiamycin did not affect (P > 0.20) postruminal or total tract digestion of
      OM, starch, NDF, and N. Compared with the control diet, monensin depressed total
      tract digestion of OM (4.2%, P = 0.03) and NDF (29.5%, P = 0.02). There were no
      treatment effects (P > 0.20) on ruminal pH, or ruminal lactate and total VFA
      molar concentration. Virginiamycin increased ruminal molar proportion of acetate
      (quadratic; P = 0.04) and estimated methane production (quadratic; P = 0.07), and
      decreased propionate molar proportion (quadratic; P = 0.09). Monensin did not
      affect (P > 0.20) ruminal VFA molar proportions or estimated methane production.
      We concluded that virginiamycin supplementation can enhance feedlot growth
      performance and dietary energetic efficiency of calf-fed Holstein steers.

PMID- 19749021
TI  - A new approach to sperm preservation based on bioenergetic theory.
AB  - To date, attempts to preserve chicken sperm have been based on a trial-and-error
      experimental approach. The present work outlines the development of an
      alternative approach based on empiricism and bioenergetic theory. In previous
      work, we found fowl sperm motility to be dependent on mitochondrial calcium
      cycling, phospholipase A(2), and long-chain fatty acids as an endogenous energy
      source. It is noteworthy that fowl sperm reside within the sperm storage tubules
      (SST) of the oviduct over an interval of days to weeks after insemination. In
      this regard, a model for in vivo sperm storage was developed and tested in
      additional previous research. Sperm penetration of the SST, sperm residence
      within the SST, and sperm egress from the SST can be explained in terms
      mitochondrial function. Understanding sperm function and longevity in terms of
      bioenergetics presented the possibility that sperm could be inactivated by
      disrupting mitochondrial calcium cycling and could thereby be preserved. However,
      this possibility also posed a problem: maintenance of the inner membrane
      potential of the mitochondrion within inactivated sperm. This report describes a
      series of experiments in which fowl sperm were inactivated by treatment with the
      calcium chelator tetrasodium 1,2-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic
      acid, and then reactivated by treatment with calcium ions. The effect of
      tetrasodium 1,2-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid on
      mitochondrial calcium cycling was confirmed by flow cytometry and confocal
      microscopy. When treated sperm were cooled to 10 degrees C, inactivated sperm
      could be reactivated throughout a 5-h storage interval. When stored sperm were
      held for 3 h before reactivation and insemination, fertility was 88% of the
      control. Storage did not affect hatchability. In summary, short-term storage was
      realized by manipulating mitochondrial function. We propose that 1) complex V
      consumes ATP within inactivated sperm and, by doing so, maintains the inner
      membrane potential of the mitochondrion, 2) ATP is regenerated within inactivated
      sperm by the action of creatine kinase on phosphocreatine, and 3) necrosis
      follows depletion of intracellular phosphocreatine. Therefore, future attempts to
      preserve chicken sperm can be based on a theory that encompasses regulation of
      energy production, a biological context in which sperm cells are motile, and the
      consequences of mitochondrial failure.

PMID- 19749022
TI  - Effects of mannanase and distillers dried grain with solubles on growth
      performance, nutrient digestibility, and carcass characteristics of grower
      finisher pigs.
AB  - Four experiments were conducted to determine the effects of dietary
      supplementation of corn distillers dried grain with solubles (DDGS) diets with
      mannanase on performance, apparent total tract digestibility (ATTD) of energy and
      nutrients, blood metabolites, and carcass characteristics of grower-finisher
      pigs. In Exp. 1, 96 grower pigs (initial BW, 57.6 kg), 6 pigs per pen and 4 pens
      per treatment, were fed corn-soybean meal-based diets containing 10% DDGS and 0,
      200, 400, or 600 units (U) of mannanase/kg. The ADG and blood glucose increased
      (linear, P < 0.05) with increasing concentrations of dietary mannanase. Pigs fed
      diets containing increasing levels of mannanase had improved ATTD of DM and CP
      (quadratic, P < 0.05). In Exp. 2, 64 finisher pigs (initial BW, 92.7 kg) were
      allotted to 4 treatment groups with 4 pigs per pen and 4 pens per treatment. Pigs
      were fed corn-soybean meal-based diets containing 15% DDGS and 0, 200, 400, or
      600 U of mannanase/kg. Linear increases (P < 0.05) in ADG, blood glucose, and
      ATTD of DM, GE, and CP were observed with increasing levels of dietary mannanase
      supplementation. In Exp. 3, 208 grower pigs (initial BW, 60.5 kg) were allotted
      to 4 treatment groups with 13 pigs per pen and 4 pens per treatment. Pigs were
      fed diets containing 0 or 10% DDGS and 0 or 400 U of mannanase/kg in a 2 x 2
      factorial arrangement. An increase (P < 0.05) in ADG and blood glucose for pigs
      fed diets containing mannanase was observed. The ATTD of DM and CP (P < 0.05) was
      decreased with the inclusion of DDGS, whereas pigs fed the mannanase-supplemented
      diets had an increased (P < 0.05) ATTD of CP. In Exp. 4, 208 finisher pigs
      (initial BW, 86.5 kg), with 13 pigs per pen and 4 pens per treatment, were fed
      diets containing 0 or 15% DDGS and 0 or 400 U of mannanase/kg in a 2 x 2
      factorial arrangement. The ADG and blood glucose increased (P < 0.05) when
      mannanase was included in the diets. The ATTD of DM (P < 0.05), GE (P < 0.10),
      and CP (P < 0.05) increased by the supplementation with mannanase in the diets of
      finisher pigs. The carcass characteristics and meat quality were not affected by
      the DDGS or mannanase inclusion. These results indicated that including 10 and
      15% DDGS in conventional swine grower and finisher diets had no detrimental
      effects on growth performance or carcass characteristics. In addition,
      supplementation with 400 U of mannanase/kg to diets containing 10 and 15% DDGS
      fed to grower and finisher pigs may improve growth performance and the ATTD of
      CP.

PMID- 19749023
TI  - Genomic selection in admixed and crossbred populations.
AB  - In livestock, genomic selection (GS) has primarily been investigated by
      simulation of purebred populations. Traits of interest are, however, often
      measured in crossbred or mixed populations with uncertain breed composition. If
      such data are used as the training data for GS without accounting for breed
      composition, estimates of marker effects may be biased due to population
      stratification and admixture. To investigate this, a genome of 100 cM was
      simulated with varying marker densities (5 to 40 segregating markers per cM).
      After 1,000 generations of random mating in a population of effective size 500, 4
      lines with effective size 100 were isolated and mated for another 50 generations
      to create 4 pure breeds. These breeds were used to generate combined, F(1), F(2),
      3- and 4-way crosses, and admixed training data sets of 1,000 individuals with
      phenotypes for an additive trait controlled by 100 segregating QTL and
      heritability of 0.30. The validation data set was a sample of 1,000 genotyped
      individuals from one pure breed. Method Bayes-B was used to simultaneously
      estimate the effects of all markers for breeding value estimation. With 5 (40)
      markers per cM, the correlation of true with estimated breeding value of
      selection candidates (accuracy) was greatest, 0.79 (0.85), when data from the
      same pure breed were used for training. When the training data set consisted of
      crossbreds, the accuracy ranged from 0.66 (0.79) to 0.74 (0.83) for the 2 marker
      densities, respectively. The admixed training data set resulted in nearly the
      same accuracies as when training was in the breed to which selection candidates
      belonged. However, accuracy was greatly reduced when genes from the target pure
      breed were not included in the admixed or crossbred population. This implies
      that, with high-density markers, admixed and crossbred populations can be used to
      develop GS prediction equations for all pure breeds that contributed to the
      population, without a substantial loss of accuracy compared with training on
      purebred data, even if breed origin has not been explicitly taken into account.
      In addition, using GS based on high-density marker data, purebreds can be
      accurately selected for crossbred performance without the need for pedigree or
      breed information. Results also showed that haplotype segments with strong
      linkage disequilibrium are shorter in crossbred and admixed populations than in
      purebreds, providing opportunities for QTL fine mapping.

PMID- 19749024
TI  - Whole genome single nucleotide polymorphism associations with feed intake and
      feed efficiency in beef cattle.
AB  - Feed intake and efficiency are economically important traits because feed is the
      greatest variable cost in beef production. Feed efficiency can be measured as
      residual feed intake (RFI), which is the difference between actual DMI of an
      animal and the expected DMI based on its BW and growth rate. Feed conversion
      ratio (FCR) is the inverse of gross feed efficiency and is the ratio of DMI to
      ADG. A total of 2,633 SNP across the 29 bovine autosomes were analyzed in 464
      steers sired by Angus, Charolais, or Alberta Hybrid bulls for associations with
      RFI. A total of 150 SNP were associated with RFI at P < 0.05 of which 23 were
      significant at P < 0.01. Nine of the SNP pairs show high linkage disequilibrium
      (r(2) > 0.80), so only 1 of the SNP pairs was used in further multiple-marker
      analyses. Two methods were used to create a panel of SNP that were maximally
      informative for RFI based on the data. In the first method, 141 unique SNP were
      combined in a single multivariate model and a backward elimination model was used
      to drop SNP until all SNP left in the model were significant at P < 0.05. The SNP
      had greater effects when combined in the multivariate model than when tested
      individually. In the second method, the estimates from the 141 SNP were used to
      create a sequential molecular breeding value (MBV) according to the compound
      covariate prediction (CCP) procedure. The sequential MBV was built by adding the
      estimated effects one at a time, but only keeping SNP effects in the sequential
      MBV if the test statistic and the proportion of variance explained were improved.
      Predictabilities of the 2 methods were compared by regressing RFI on a final MBV
      created from SNP that remained in each analytical model. The MBV from the
      compound covariate prediction model produced an r(2) of 0.497, whereas the
      multivariate model MBV had a decreased r(2) of 0.416. The significant SNP were
      also tested for associations with DMI and FCR. The SNP showed different
      combinations of associations with the 4 traits, including some that were only
      associated with RFI. About 9.5% of the SNP from the 2 models were within 5 cM of
      previously identified RFI QTL and pinpoint areas to further explore for
      positional candidate genes. In conclusion, this study has identified a panel of
      SNP with significant effects on RFI that need to be validated in an independent
      population and provides continued progress toward selecting markers for use in
      marker-assisted selection for feed efficiency in beef cattle.

PMID- 19749025
TI  - Effects of water quality and dietary potassium on performance and carcass
      characteristics of yearling steers.
AB  - Four hundred thirty-two crossbred yearling steers (339 kg +/- 4.8) were used to
      investigate the effects of water quality and dietary potassium concentration and
      source on feedlot performance and carcass merit. The study was conducted using a
      2 x 3 factorial treatment arrangement. Factors evaluated included 2 water
      sources: 1) a blend of reverse osmosis and well water (RO; 608 +/- 164 mg/L of
      SO(4)) and 2) 100% well water with SO(4) concentration of 1,933 +/- 53 mg/L and 3
      dietary K treatments. Potassium treatments included 0.75% K with supplemental K
      from potassium chloride (0.75% K-KCl), 0.75% K with supplemental K from potassium
      carbonate (0.75% K-K(2)CO(3)), and 1.0% K with supplemental K from potassium
      carbonate (1.0% K-K(2)CO(3)). Interactions between water quality and dietary
      treatments were not significant. Dry matter intake tended (P = 0.10) to be
      greater for steers consuming RO water compared with well water and was not
      affected by dietary treatment. Feed efficiency (P = 0.04) and NE(g) recovery (P =
      0.04) were greater for 1.0% K-K(2)CO(3) compared with 0.75% K-KCl but were not
      affected by water quality. Final BW was heavier (P < 0.001) and ADG was greater
      (P = 0.04) for RO water compared with well water but were not affected by diet.
      Carcasses from steers that consumed RO water tended (P = 0.08) to be heavier than
      carcasses from steers consuming well water. Dietary treatment did not affect HCW
      (P = 0.52). Yield grade calculated from carcass measurements was not affected by
      dietary treatment or water quality. Carcasses from steers consuming well water
      had greater (P = 0.04) marbling scores than RO water. These data demonstrate that
      steers consuming RO water achieved improved feedlot performance. Steers fed 1.0%
      K-K(2)CO(3) were more efficient and demonstrated improved energy recovery
      compared with steers fed 0.75% K-KCl. Improved efficiency and energy recovery may
      be related to a reduction (P = 0.06) in the liver abscess rate for steers
      consuming 1.0% K-K(2)CO(3). Dietary cation-anion balance was positively related
      to ADG (P < 0.01) and NE(g) (P = 0.03) recovery but negatively related to
      marbling score (P = 0.04).

PMID- 19749026
TI  - Cohort profile: research on Osteoarthritis/Osteoporosis Against Disability study.

PMID- 19749027
TI  - Safety aspects of 36 months of administration of long-acting intramuscular
      testosterone undecanoate for treatment of female-to-male transgender individuals.
AB  - DESIGN: Testosterone treatment is essential for the induction and maintenance of
      virilization of female-to-male (FTM) transsexuals. Aim To test the safety of a
      novel testosterone preparation for this purpose. METHODS: Parenteral long-acting
      testosterone undecanoate (TU) was administered to 17 FTM transsexuals over 36
      months. Observations were made while subjects received treatment. RESULTS: Serum
      testosterone rose from 0.50+/-0.25 to 6.2+/-1.3 ng/ml at 6 months and remained
      stable thereafter. The testosterone profiles were largely identical with those in
      hypogonadal receiving TU. There were no side effects. Over the 36 months of the
      study, there was a small but significant decrease in plasma cholesterol (from
      218+/-47 to 188+/-42 mg/dl) and low-density lipoprotein-cholesterol (from 139+/
      48 to 139+/-48 mg/dl), while plasma levels of high-density lipoprotein
      cholesterol and triglycerides did not change significantly. Liver enzymes did not
      change during treatment. There was an increase of both levels in hemoglobin (from
      13.6+/-1.2 to 16.0+/-1.5 g/dl) and hematocrit (from 41+/-4 to 46+/-4) upon
      administration but they remained almost without exception within the
      physiological range. No special measures were needed. Breast and gonads/internal
      genitalia did not show pathological changes over the observation period.
      CONCLUSION: This study reports that TU is suited for induction of virilization in
      FTM transsexuals without significant side effects over a longer term.

PMID- 19749028
TI  - Pusillimonas ginsengisoli sp. nov., isolated from soil of a ginseng field.
AB  - Two novel strains of Gram-negative, non-sporulating, short rod-shaped, motile
      bacteria, designated DCY25T and DCY28, were isolated from soil of a ginseng field
      in South Korea and characterized in order to determine their taxonomic position.
      16S rRNA gene sequence analysis showed that strains DCY25T and DCY28 belonged to
      the Betaproteobacteria, the highest sequence similarities being found with
      Pusillimonas noertemannii BN9T (96.9%), Bordetella trematum DSM 11334(T) (95.9%),
      Achromobacter denitrificans DSM 30026T (95.9%), Achromobacter insolitus LMG 6003T
      (95.8%) and Pigmentiphaga kullae K24T (95.5%). Chemotaxonomic data revealed that
      both strains DCY25T and DCY28 possessed ubiquinone Q-8. Fatty acid analysis of
      strain DCY25T demonstrated the presence of 19:0 cyclo omega8c (22.8%) and 16:0
      (16.6%). The polar lipid profiles of strains DCY25T and DCY28 included
      phosphatidylethanolamine, phosphatidylglycerol, two unknown aminolipids and
      diphosphatidylglycerol. The G+C contents of strains DCY25T and DCY28 were 57.3
      and 57.2 mol%, respectively. DNA-DNA relatedness values, biochemical and
      physiological characteristics strongly supported the genotypic and phenotypic
      differentiation of strains DCY25T and DCY28 from Pusillimonas noertemannii.
      Therefore, strains DCY25T and DCY28 should be classified in a novel species, for
      which the name Pusillimonas ginsengisoli sp. nov. is proposed. The type strain is
      DCY25T (=KCTC 22046T =JCM 14767T); strain DCY28 (=KCTC 22047=JCM 14768) is a
      reference strain.

PMID- 19749029
TI  - Succinatimonas hippei gen. nov., sp. nov., isolated from human faeces.
AB  - A novel strictly anaerobic, non-spore-forming, non-motile, non-flagellated, rod
      shaped, Gram-negative bacterium (YIT 12066T) was isolated from human faeces. The
      isolate was negative for catalase, oxidase, urease, hydrolysis of aesculin and
      gelatin, nitrate reduction and indole production. The major end products of
      glucose metabolism were succinate and acetate. The major cellular fatty acids
      (>10%) were C14:0, C18:1omega7c, C18:1omega9c, C16:1omega7c and C16:0. The G+C
      content of the DNA was 40.3 mol%. 16S rRNA gene sequence analysis showed that
      strain YIT 12066T was most closely related to members of the family
      Succinivibrionaceae, with sequence similarity of 92-87%. However, some phenotypic
      characteristics such as cellular morphology and the major fatty acid profile of
      strain YIT 12066T were markedly different from those of other members of the
      family Succinivibrionaceae. On the basis of both phylogenetic and phenotypic
      evidence, it is suggested that strain YIT 12066T represents a novel species in a
      new genus, for which the name Succinatimonas hippei gen. nov., sp. nov. is
      proposed; the type strain of Succinatimonas hippei is YIT 12066T (=DSM 22608T
      =JCM 16073T).

PMID- 19749030
TI  - Marinitoga litoralis sp. nov., a thermophilic, heterotrophic bacterium isolated
      from a coastal thermal spring on Ile Saint-Paul, Southern Indian Ocean.
AB  - A novel thermophilic, anaerobic and organotrophic bacterium, designated strain
      MC3T, was isolated from a coastal thermal spring on Ile Saint-Paul in the
      Southern Indian Ocean. Cells of strain MC3T were motile rods, 0.8-1.0 microm wide
      and 1.0-2.4 microm long during exponential phase and up to 7.0 microm long during
      stationary phase. Strain MC3T was an anaerobic organotroph able to use diverse
      organic compounds. It was also able to reduce sulfur to sulfide. Growth was
      observed at temperatures ranging from 45 to 70 degrees C (optimum at 60 degrees
      C), between pH 5.5 and 7.5 (optimum at pH 6) and from 8 to 46 g NaCl l(-1)
      (optimum at 26 g l(-1)). The total G+C content of the genomic DNA was 26.2 mol%.
      Phylogenetic analysis based on 16S rRNA gene sequence comparisons indicated that
      strain MC3T was affiliated with the genus Marinitoga within the order
      Thermotogales. It shared 94.4-95.7% 16S rRNA gene sequence similarity with
      strains of other Marinitoga species; Marinitoga hydrogenitolerans was found to be
      the most closely related organism. Based on the data from the phylogenetic
      analysis and the physiological properties of the novel isolate, strain MC3T
      should be classified as a representative of a novel species, for which the name
      Marinitoga litoralis sp. nov. is proposed; the type strain is MC3T (=DSM 21709T
      =JCM 15581T).

PMID- 19749031
TI  - An SSU rDNA barcoding approach to the diversity of marine interstitial
      cercozoans, including descriptions of four novel genera and nine novel species.
AB  - Environmental DNA surveys have revealed a great deal of hidden diversity within
      the Cercozoa. An investigation into the biodiversity of heterotrophic flagellates
      in marine benthic habitats of British Columbia, Canada, demonstrated the presence
      of several undescribed taxa with morphological features that resemble the
      cercozoan genera Cryothecomonas and Protaspis. Nine novel species of marine
      interstitial cercozoans are described that are distributed into five genera, four
      of which are new. Phylogenetic analyses of small subunit rDNA sequences derived
      from two uncultured isolates of Protaspis obliqua and nine novel cercozoan
      species (within four novel genera) provided organismal anchors that helped
      establish the cellular identities of several different environmental sequence
      clades. These data, however, also showed that the rarity of distinctive
      morphological features in cryomonads, and other groups of cercozoans, makes the
      identification and systematics of the group very difficult. Therefore, a DNA
      barcoding approach was applied as a diagnostic tool for species delimitation that
      used a 618 bp region at the 5' end of the SSU rDNA sequence. Nucleotide sequence
      analysis of this region showed high intergeneric sequence divergences of about 7%
      and very low intraspecific sequence divergences of 0-0.5%; phylogenetic analyses
      inferred from this barcoding region showed very similar tree topologies to those
      inferred from the full-length sequence of the gene. Overall, this study indicated
      that the 618 bp barcoding region of SSU rDNA sequences is a useful molecular
      signature for understanding the biodiversity and interrelationships of marine
      benthic cercozoans.

PMID- 19749032
TI  - Chryseobacterium arthrosphaerae sp. nov., isolated from the faeces of the pill
      millipede Arthrosphaera magna Attems.
AB  - A bacterial strain (CC-VM-7T), isolated from the faeces of the pill millipede
      Arthrosphaera magna Attems collected in India, was studied to determine its
      taxonomic allocation. Cells stained Gram-negative and were rod-shaped.
      Comparative analyses of the 16S rRNA gene sequence of the strain with those of
      the most closely related species clearly suggested allocation to the genus
      Chryseobacterium, with the highest sequence similarities of 99.2% to
      Chryseobacterium gleum CCUG 14555T, 98.6% to Chryseobacterium indologenes CCUG
      14556T and 98.4% to Chryseobacterium aquifrigidense KCTC 12894T. 16S rRNA gene
      sequence similarities to all other species of the genus Chryseobacterium were
      below 98%. The major whole-cell fatty acids were iso-C15:0 and iso-C17:1omega9c.
      DNA-DNA hybridization resulted in relatedness values of only 29.6% (reciprocal
      31.3%) to Chryseobacterium gleum CCUG 14555T, 41.2% (reciprocal 38.8%) to C.
      indologenes CCUG 14556T and 35.4% (reciprocal 38.5%) to C. aquifrigidense KCTC
      12894T. DNA-DNA relatedness, biochemical and chemotaxonomic properties clearly
      show that strain CC-VM-7T represents a novel species, for which the name
      Chryseobacterium arthrosphaerae sp. nov. is proposed. The type strain is CC-VM-7T
      (=CCUG 57618T =CCM 7645T).

PMID- 19749033
TI  - Streptomyces osmaniensis sp. nov., isolated from soil.
AB  - A novel actinomycete, designated strain OU-63T, was isolated from garden soil
      collected on the campus of Osmania University in Hyderabad, southern India. The
      strain was found to have morphological and chemotaxonomic characteristics typical
      of the genus Streptomyces. Phylogenetic analysis based on 16S rRNA gene sequences
      indicated that the strain belonged to the genus Streptomyces, and was related
      most closely to Streptomyces chartreusis NBRC 12753T (98.6% similarity). However,
      the mean level of DNA-DNA relatedness between the two strains was only 25+/
      1.73%. Based on DNA-DNA relatedness, morphological and phenotypic data, strain OU
      63T could be distinguished from the type strains of phylogenetically related
      species. It is therefore considered to represent a novel species of the genus
      Streptomyces, for which the name Streptomyces osmaniensis sp. nov. is proposed.
      The type strain is OU-63T (=CCTCC AA209025T =PCM 2690T).

PMID- 19749034
TI  - Chitinibacter alvei sp. nov., isolated from stream water.
AB  - A Gram-negative, aerobic bacterium, designated strain TNR-14T, was isolated from
      water of a stream located in southern Taiwan. Cells were rod-shaped and motile by
      means of a polar flagellum. The isolate exhibited optimum growth at 20 degrees C,
      at pH 7.0 and in the absence of NaCl. Phylogenetic analyses based on 16S rRNA
      gene sequences showed that the strain belonged to the genus Chitinibacter and was
      related most closely to the type strain of Chitinibacter tainanensis (96.0%
      similarity). The predominant cellular fatty acids were summed feature 3
      (C16:1omega7c and/or C16:1omega6c; 54.03%) and C16:0 (27.22%). The DNA G+C
      content of strain TNR-14T was 57.5 mol%. The results of physiological and
      biochemical tests and chemotaxonomic data allowed the clear phenotypic
      differentiation of the new isolate from Chitinibacter tainanensis. Strain TNR-14T
      is therefore considered to represent a novel species of the genus Chitinibacter,
      for which the name Chitinibacter alvei sp. nov. is proposed. The type strain is
      TNR-14T (=LMG 25206T =DSM 22217T =BCRC 17968T).

PMID- 19749035
TI  - Tateyamaria pelophila sp. nov., a facultatively anaerobic alphaproteobacterium
      isolated from tidal-flat sediment, and emended descriptions of the genus
      Tateyamaria and of Tateyamaria omphalii.
AB  - A Gram-negative motile rod, strain SAM4T, was isolated from the highest positive
      dilution of a most probable number series inoculated with tidal-flat sediments
      from the German North Sea coast. The isolate grew at 4-35 degrees C and showed
      constant growth yields throughout almost the whole temperature range. Growth was
      observed between pH 6 and 9 and at salinities of 0.3-10.2%. Strain SAM4T required
      Na+ for growth, contained bacteriochlorophyll a and was catalase- and oxidase
      positive. It was nutritionally versatile growing on a variety of carbon compounds
      including carbohydrates, amino acids and organic acids like lactate or succinate.
      It grew anaerobically on complex media such as marine broth, indicating
      fermentation, and by reducing trimethylammonium oxide. The dominant phospholipids
      were phosphatidylethanolamine and phosphatidylglycerol, whereas only traces of
      phosphatidylcholine and an unidentified lipid were found. The major fatty acid
      was n-C18:1omega7c. The DNA G+C content was 56.4 mol%. The isolate was identified
      as a member of the Roseobacter clade within the class Alphaproteobacteria.
      However, based on phylogenetic, phenotypic and physiological data, it clearly
      differs from its closest relative Tateyamaria omphalii. Therefore, a novel
      species is proposed: Tateyamaria pelophila sp. nov., with strain SAM4T (=DSM
      17270T=LMG 23018T) as the type strain. Emended descriptions of the genus
      Tateyamaria and of Tateyamaria omphalii are also presented.

PMID- 19749036
TI  - Vibrio casei sp. nov., isolated from the surfaces of two French red smear soft
      cheeses.
AB  - Three Gram-negative, rod-shaped, catalase- and oxidase-positive, facultatively
      anaerobic and motile bacteria, strains WS 4538, WS 4539T and WS 4540, were
      isolated from the surfaces of two fully ripened French red smear soft cheeses.
      Based on 16S rRNA gene sequence similarity, all three strains were shown to
      belong to the genus Vibrio. They are most closely related to Vibrio rumoiensis S
      1T (96.3% similarity) and Vibrio litoralis MANO22DT (95.9%). DNA-DNA
      hybridization confirmed that all three isolates belong to the same species and
      clearly separated strain WS 4539T from V. rumoiensis DSM 19141T (38-42%
      relatedness) and V. litoralis DSM 17657(T) (28-37%). In contrast to their nearest
      relatives, the strains exhibited beta-galactosidase and aesculin hydrolase
      activities. A 14 bp insertion in the 16S rRNA gene sequence forms an elongated
      structure at helix 10 in the rRNA molecule and provides a tool for PCR-based
      identification of the novel species. Partial sequences of the housekeeping genes
      atpA, recA, rpoA and pyrH supported the conclusion that the three isolates
      constitute a separate species within the genus Vibrio. The name Vibrio casei sp.
      nov. is proposed for the novel taxon. Strain WS 4539T (=DSM 22364T =LMG 25240T;
      DNA G+C content 41.8 mol%) is the type strain and WS 4540 (=DSM 22378 =LMG 25241)
      is a reference strain.

PMID- 19749037
TI  - Amorphus orientalis sp. nov., an exopolysaccharide-producing bacterium isolated
      from salt mine sediment.
AB  - A Gram-negative, moderately halophilic, non-motile, aerobic bacterium, designated
      strain YIM D10T, was isolated from a salt mine sediment sample from Yunnan, south
      west China. The strain grew optimally in the presence of 3-8% NaCl and at 28
      degrees C and pH 7.5. The polar lipid profile of strain YIM D10T comprised
      diphosphatidylglycerol, an unknown phospholipid and two unknown aminolipids. The
      major cellular fatty acids were C18:1omega7c (30.5%), C19:0 cyclo omega8c (29.3%)
      and C18:0 (13.2%). The respiratory quinone was ubiquinone 10 (Q-10). The genomic
      DNA G+C content was 65.4 mol%. Phylogenetic analysis based on 16S rRNA gene
      sequences showed that strain YIM D10T was closely related to Amorphus coralli
      RS.Sph.026T (96.8% gene sequence similarity). Results confirmed the placement of
      isolate YIM D10T within the genus Amorphus. However, DNA-DNA hybridization
      between strain YIM D10T and the type strain of the only recognized species of the
      genus Amorphus, A. coralli RS.Sph.026T, was 16.7%, showing clearly that the
      isolate constitutes a new genospecies. Strain YIM D10T could be clearly
      differentiated from A. coralli and other phylogenetic neighbours on the basis of
      some phenotypic, genotypic and chemotaxonomic features. Therefore, strain YIM
      D10T is considered to represent a novel species of the genus Amorphus, for which
      the name Amorphus orientalis sp. nov. is proposed; the type strain is YIM D10T
      (=DSM 21202T=CCTCC AA 208035T).

PMID- 19749038
TI  - Motility and flagellar glycosylation in Clostridium difficile.
AB  - In this study, intact flagellin proteins were purified from strains of
      Clostridium difficile and analyzed using quadrupole time of flight and linear ion
      trap mass spectrometers. Top-down studies showed the flagellin proteins to have a
      mass greater than that predicted from the corresponding gene sequence. These top
      down studies revealed marker ions characteristic of glycan modifications.
      Additionally, diversity in the observed masses of glycan modifications was seen
      between strains. Electron transfer dissociation mass spectrometry was used to
      demonstrate that the glycan was attached to the flagellin protein backbone in O
      linkage via a HexNAc residue in all strains examined. Bioinformatic analysis of
      C. difficile genomes revealed diversity with respect to glycan biosynthesis gene
      content within the flagellar biosynthesis locus, likely reflected by the observed
      flagellar glycan diversity. In C. difficile strain 630, insertional inactivation
      of a glycosyltransferase gene (CD0240) present in all sequenced genomes resulted
      in an inability to produce flagellar filaments at the cell surface and only minor
      amounts of unmodified flagellin protein.

PMID- 19749039
TI  - Laboratory strains of Bacillus subtilis do not exhibit swarming motility.
AB  - We redemonstrate that SwrA is essential for swarming motility in Bacillus
      subtilis, and we reassert that laboratory strains of B. subtilis do not swarm.
      Additionally, we find that a number of other genes, previously reported to be
      required for swarming in laboratory strains, are dispensable for robust swarming
      motility in an undomesticated strain. We attribute discrepancies in the
      literature to a lack of reproducible standard experimental conditions, selection
      for spontaneous swarming suppressors, inadvertent genetic linkage to swarming
      mutations, and auxotrophy.

PMID- 19749040
TI  - Envelope proteins of the CsmB/CsmF and CsmC/CsmD motif families influence the
      size, shape, and composition of chlorosomes in Chlorobaculum tepidum.
AB  - The chlorosome envelope of Chlorobaculum tepidum contains 10 proteins that belong
      to four structural motif families. A previous mutational study (N.-U. Frigaard,
      H. Li, K. J. Milks, and D. A. Bryant, J. Bacteriol. 186:646-653, 2004) suggested
      that some of these proteins might have redundant functions. Six multilocus
      mutants were constructed to test the effects of eliminating the proteins of the
      CsmC/CsmD and CsmB/CsmF motif families, and the resulting strains were
      characterized physiologically and biochemically. Mutants lacking all proteins of
      either motif family still assembled functional chlorosomes, and as measured by
      growth rates of the mutant strains, light harvesting was affected only at the
      lowest light intensities tested (9 and 32 micromol photons m(-2) s(-1)). The
      size, composition, and biogenesis of the mutant chlorosomes differed from those
      of wild-type chlorosomes. Mutants lacking proteins of the CsmC/CsmD motif family
      produced smaller chlorosomes than did the wild type, and the Q(y) absorbance
      maximum for the bacteriochlorophyll c aggregates in these chlorosomes was
      strongly blueshifted. Conversely, the chlorosomes of mutants lacking proteins of
      the CsmB/CsmF motif family were larger than wild-type chlorosomes, and the Q(y)
      absorption for their bacteriochlorophyll c aggregates was redshifted. When CsmH
      was eliminated in addition to other proteins of either motif family, chlorosomes
      had smaller diameters. These data show that the chlorosome envelope proteins of
      the CsmB/CsmF and CsmC/CsmD families play important roles in determining
      chlorosome size as well as the assembly and supramolecular organization of the
      bacteriochlorophyll c aggregates within the chlorosome.

PMID- 19749041
TI  - Genetic and biochemical analysis of the interaction of Bacillus subtilis CodY
      with branched-chain amino acids.
AB  - Bacillus subtilis CodY protein is a DNA-binding global transcriptional regulator
      that responds to branched-chain amino acids (isoleucine, leucine, and valine) and
      GTP. Crystal structure studies have shown that the N-terminal region of the
      protein includes a GAF domain that contains a hydrophobic pocket within which
      isoleucine and valine bind. This region is well conserved in CodY homologs. Site
      directed mutagenesis was employed to understand the roles of some of the residues
      in the GAF domain and hydrophobic pocket in interaction with isoleucine and GTP.
      The F40A, F71E, and F98A forms of CodY were inactive in vivo. They were
      activatable by GTP but to a much lesser extent by branched-chain amino acids in
      vitro. The CodY mutant R61A retained partial repression of target promoters in
      vivo and was able to respond to GTP in vitro but also responded poorly to
      branched-chain amino acids in vitro unless GTP was simultaneously present. Thus,
      the GAF domain includes residues essential for full activation of CodY by
      branched-chain amino acids, but these residues are not critical for activation by
      GTP. Binding studies with branched-chain amino acids and their analogs revealed
      that an amino group at position 2 and a methyl group at position 3 of valine are
      critical components of the recognition of the amino acids by CodY.

PMID- 19749042
TI  - Repeat-associated plasticity in the Helicobacter pylori RD gene family.
AB  - The bacterium Helicobacter pylori is remarkable for its ability to persist in the
      human stomach for decades without provoking sterilizing immunity. Since
      repetitive DNA can facilitate adaptive genomic flexibility via increased
      recombination, insertion, and deletion, we searched the genomes of two H. pylori
      strains for nucleotide repeats. We discovered a family of genes with extensive
      repetitive DNA that we have termed the H. pylori RD gene family. Each gene of
      this family is composed of a conserved 3' region, a variable mid-region encoding
      7 and 11 amino acid repeats, and a 5' region containing one of two possible
      alleles. Analysis of five complete genome sequences and PCR genotyping of 42 H.
      pylori strains revealed extensive variation between strains in the number,
      location, and arrangement of RD genes. Furthermore, examination of multiple
      strains isolated from a single subject's stomach revealed intrahost variation in
      repeat number and composition. Despite prior evidence that the protein products
      of this gene family are expressed at the bacterial cell surface, enzyme-linked
      immunosorbent assay and immunoblot studies revealed no consistent seroreactivity
      to a recombinant RD protein by H. pylori-positive hosts. The pattern of repeats
      uncovered in the RD gene family appears to reflect slipped-strand mispairing or
      domain duplication, allowing for redundancy and subsequent diversity in genotype
      and phenotype. This novel family of hypervariable genes with conserved,
      repetitive, and allelic domains may represent an important locus for
      understanding H. pylori persistence in its natural host.

PMID- 19749043
TI  - YjhS (NanS) is required for Escherichia coli to grow on 9-O-acetylated N
      acetylneuraminic acid.
AB  - The nanATEK-yhcH, yjhATS, and yjhBC operons in Escherichia coli are coregulated
      by environmental N-acetylneuraminic acid, the most prevalent sialic acid in
      nature. Here we show that YjhS (NanS) is a probable 9-O-acetyl N-acetylneuraminic
      acid esterase required for E. coli to grow on this alternative sialic acid, which
      is commonly found in mammalian host mucosal sites.

PMID- 19749044
TI  - Depletion of the signal recognition particle receptor inactivates ribosomes in
      Escherichia coli.
AB  - The signal recognition particle (SRP)-dependent cotranslational targeting of
      proteins to the cytoplasmic membrane in bacteria or the endoplasmic reticulum
      membrane in eukaryotes is an essential process in most living organisms.
      Eukaryotic cells have been shown to respond to an impairment of the SRP pathway
      by (i) repressing ribosome biogenesis, resulting in decreased protein synthesis,
      and (ii) by increasing the expression of protein quality control mechanisms, such
      as chaperones and proteases. In the current study, we have analyzed how bacteria
      like Escherichia coli respond to a gradual depletion of FtsY, the bacterial SRP
      receptor. Our analyses using cell-free transcription/translation systems showed
      that FtsY depletion inhibits the translation of both SRP-dependent and SRP
      independent proteins. This synthesis defect is the result of a multifaceted
      response that includes the upregulation of the ribosome-inactivating protein
      ribosome modulation factor (RMF). Although the consequences of these responses in
      E. coli are very similar to some of the effects also observed in eukaryotic
      cells, one striking difference is that E. coli obviously does not reduce the rate
      of protein synthesis by downregulating ribosome biogenesis. Instead, the
      upregulation of RMF leads to a direct and reversible inhibition of translation.

PMID- 19749045
TI  - Evidence that human Chlamydia pneumoniae was zoonotically acquired.
AB  - Zoonotic infections are a growing threat to global health. Chlamydia pneumoniae
      is a major human pathogen that is widespread in human populations, causing acute
      respiratory disease, and has been associated with chronic disease. C. pneumoniae
      was first identified solely in human populations; however, its host range now
      includes other mammals, marsupials, amphibians, and reptiles. Australian koalas
      (Phascolarctos cinereus) are widely infected with two species of Chlamydia, C.
      pecorum and C. pneumoniae. Transmission of C. pneumoniae between animals and
      humans has not been reported; however, two other chlamydial species, C. psittaci
      and C. abortus, are known zoonotic pathogens. We have sequenced the 1,241,024-bp
      chromosome and a 7.5-kb cryptic chlamydial plasmid of the koala strain of C.
      pneumoniae (LPCoLN) using the whole-genome shotgun method. Comparative genomic
      analysis, including pseudogene and single-nucleotide polymorphism (SNP)
      distribution, and phylogenetic analysis of conserved genes and SNPs against the
      human isolates of C. pneumoniae show that the LPCoLN isolate is basal to human
      isolates. Thus, we propose based on compelling genomic and phylogenetic evidence
      that humans were originally infected zoonotically by an animal isolate(s) of C.
      pneumoniae which adapted to humans primarily through the processes of gene decay
      and plasmid loss, to the point where the animal reservoir is no longer required
      for transmission.

PMID- 19749046
TI  - The terminal A domain of the fibrillar accumulation-associated protein (Aap) of
      Staphylococcus epidermidis mediates adhesion to human corneocytes.
AB  - The opportunistic pathogen Staphylococcus epidermidis colonizes indwelling
      medical devices by biofilm formation but is primarily a skin resident. In many S.
      epidermidis strains biofilm formation is mediated by a cell wall-anchored
      protein, the accumulation-associated protein (Aap). Here, we investigate the role
      of Aap in skin adhesion. Aap is an LPXTG protein with a domain architecture
      including a terminal A domain and a B-repeat region. S. epidermidis NCTC 11047
      expresses Aap as localized, lateral tufts of fibrils on one subpopulation of
      cells (Fib(+)), whereas a second subpopulation does not express these fibrils of
      Aap (Fib(-)). Flow cytometry showed that 72% of NCTC 11047 cells expressed Aap
      and that 28% of cells did not. Aap is involved in the adhesion of Fib(+) cells to
      squamous epithelial cells from the hand (corneocytes), as the recombinant A
      domain protein partially blocked binding to corneocytes. To confirm the role of
      the Aap A domain in corneocyte attachment, Aap was expressed on the surface of
      Lactococcus lactis MG1363 as sparsely distributed, peritrichous fibrils. The
      expression of Aap increased corneocyte adhesion 20-fold compared to L. lactis
      carrying Aap without an A domain. S. epidermidis isolates from catheters,
      artificial joints, skin, and the nose also used the A domain of Aap to adhere to
      corneocytes, emphasizing the role of Aap in skin adhesion. In addition, L. lactis
      expressing Aap with different numbers of B repeats revealed a positive
      correlation between the number of B repeats and adhesion to corneocytes,
      suggesting an additional function for the B region in enhancing A-domain
      dependent attachment to skin. Therefore, in addition to its established role in
      biofilm formation, Aap can also promote adhesion to corneocytes and is likely to
      be an important adhesin in S. epidermidis skin colonization.

PMID- 19749047
TI  - Functional characterization of flagellin glycosylation in Campylobacter jejuni 81
      176.
AB  - The major flagellin of Campylobacter jejuni strain 81-176, FlaA, has been shown
      to be glycosylated at 19 serine or threonine sites, and this glycosylation is
      required for flagellar filament formation. Some enzymatic components of the
      glycosylation machinery of C. jejuni 81-176 are localized to the poles of the
      cell in an FlhF-independent manner. Flagellin glycosylation could be detected in
      flagellar mutants at multiple levels of the regulatory hierarchy, indicating that
      glycosylation occurs independently of the flagellar regulon. Mutants were
      constructed in which each of the 19 serine or threonines that are glycosylated in
      FlaA was converted to an alanine. Eleven of the 19 mutants displayed no
      observable phenotype, but the remaining 8 mutants had two distinct phenotypes.
      Five mutants (mutations S417A, S436A, S440A, S457A, and T481A) were fully motile
      but defective in autoagglutination (AAG). Three other mutants (mutations S425A,
      S454A, and S460A) were reduced in motility and synthesized truncated flagellar
      filaments. The data implicate certain glycans in mediating filament-filament
      interactions resulting in AAG and other glycans appear to be critical for
      structural subunit-subunit interactions within the filament.

PMID- 19749048
TI  - Identification of functional LsrB-like autoinducer-2 receptors.
AB  - Although a variety of bacterial species have been reported to use the
      interspecies communication signal autoinducer-2 (AI-2) to regulate multiple
      behaviors, the molecular mechanisms of AI-2 recognition and signal transduction
      remain poorly understood. To date, two types of AI-2 receptors have been
      identified: LuxP, present in Vibrio spp., and LsrB, first identified in
      Salmonella enterica serovar Typhimurium. In S. Typhimurium, LsrB is the ligand
      binding protein of a transport system that enables the internalization of AI-2.
      Here, using both sequence analysis and structure prediction, we establish a set
      of criteria for identifying functional AI-2 receptors. We test our predictions
      experimentally, assaying key species for their abilities to import AI-2 in vivo,
      and test their LsrB orthologs for AI-2 binding in vitro. Using these experimental
      approaches, we were able to identify AI-2 receptors in organisms belonging to
      phylogenetically distinct families such as the Enterobacteriaceae, Rhizobiaceae,
      and Bacillaceae. Phylogenetic analysis of LsrB orthologs indicates that this
      pattern could result from one single origin of the functional LsrB gene in a
      gammaproteobacterium, suggesting possible posterior independent events of lateral
      gene transfer to the Alphaproteobacteria and Firmicutes. Finally, we used
      mutagenesis to show that two AI-2-interacting residues are essential for the AI-2
      binding ability. These two residues are conserved in the binding sites of all the
      functional AI-2 binding proteins but not in the non-AI-2-binding orthologs.
      Together, these results strongly support our ability to identify functional LsrB
      type AI-2 receptors, an important step in investigations of this interspecies
      signal.

PMID- 19749049
TI  - Mutualistic biofilm communities develop with Porphyromonas gingivalis and
      initial, early, and late colonizers of enamel.
AB  - Porphyromonas gingivalis is present in dental plaque as early as 4 h after tooth
      cleaning, but it is also associated with periodontal disease, a late-developing
      event in the microbial successions that characterize daily plaque development. We
      report here that P. gingivalis ATCC 33277 is remarkable in its ability to
      interact with a variety of initial, early, middle, and late colonizers growing
      solely on saliva. Integration of P. gingivalis into multispecies communities was
      investigated by using two in vitro biofilm models. In flow cells, bacterial
      growth was quantified using fluorescently conjugated antibodies against each
      species, and static biofilm growth on saliva-submerged polystyrene pegs was
      analyzed by quantitative real-time PCR using species-specific primers. P.
      gingivalis could not grow as a single species or together with initial colonizer
      Streptococcus oralis but showed mutualistic growth when paired with two other
      initial colonizers, Streptococcus gordonii and Actinomyces oris, as well as with
      Veillonella sp. (early colonizer), Fusobacterium nucleatum (middle colonizer),
      and Aggregatibacter actinomycetemcomitans (late colonizer). In three-species flow
      cells, P. gingivalis grew with Veillonella sp. and A. actinomycetemcomitans but
      not with S. oralis and A. actinomycetemcomitans. Also, it grew with Veillonella
      sp. and F. nucleatum but not with S. oralis and F. nucleatum, indicating that P.
      gingivalis and S. oralis are not compatible. However, P. gingivalis grew in
      combination with S. gordonii and S. oralis, demonstrating its ability to overcome
      the incompatibility when cultured with a second initially colonizing species.
      Collectively, these data help explain the observed presence of P. gingivalis at
      all stages of dental plaque development.

PMID- 19749050
TI  - Archaeal intrinsic transcription termination in vivo.
AB  - Thermococcus kodakarensis (formerly Thermococcus kodakaraensis) strains have been
      constructed with synthetic and natural DNA sequences, predicted to function as
      archaeal transcription terminators, identically positioned between a constitutive
      promoter and a beta-glycosidase-encoding reporter gene (TK1761). Expression of
      the reporter gene was almost fully inhibited by the upstream presence of 5'
      TTTTTTTT (T(8)) and was reduced >70% by archaeal intergenic sequences that
      contained oligo(T) sequences. An archaeal intergenic sequence (t(mcrA)) that
      conforms to the bacterial intrinsic terminator motif reduced TK1761 expression
      approximately 90%, but this required only the oligo(T) trail sequence and not the
      inverted-repeat and loop region. Template DNAs were amplified from each T.
      kodakarensis strain, and transcription in vitro by T. kodakarensis RNA polymerase
      was terminated by sequences that reduced TK1761 expression in vivo. Termination
      occurred at additional sites on these linear templates, including at a 5'
      AAAAAAAA (A(8)) sequence that did not reduce TK1761 expression in vivo. When
      these sequences were transcribed on supercoiled plasmid templates, termination
      occurred almost exclusively at oligo(T) sequences. The results provide the first
      in vivo experimental evidence for intrinsic termination of archaeal transcription
      and confirm that archaeal transcription termination is stimulated by oligo(T)
      sequences and is different from the RNA hairpin-dependent mechanism established
      for intrinsic bacterial termination.

PMID- 19749051
TI  - Cyclic-di-GMP-binding CRP-like protein: a spectacular new role for a veteran
      signal transduction actor.

PMID- 19749052
TI  - A new twist on a classic paradigm: illumination of a genetic switch in Vibrio
      cholerae phage CTX Phi.

PMID- 19749053
TI  - Identification of the UDP-N-acetylglucosamine 4-epimerase involved in exosporium
      protein glycosylation in Bacillus anthracis.
AB  - Spores of Bacillus anthracis, the causative agent of anthrax, are enclosed by a
      loosely fitting exosporium composed of a basal layer and an external hair-like
      nap. The filaments of the nap are formed by trimers of the collagen-like
      glycoprotein BclA. The side chains of BclA include multiple copies of two linear
      rhamnose-containing oligosaccharides, a trisaccharide and a pentasaccharide. The
      pentasaccharide terminates with the unusual deoxyamino sugar anthrose. Both
      oligosaccharide side chains are linked to the BclA protein backbone through an N
      acetylgalactosamine (GalNAc) residue. To identify the gene encoding the epimerase
      required to produce GalNAc for BclA oligosaccharide biosynthesis, three annotated
      UDP-glucose 4-epimerase genes of B. anthracis were cloned and expressed in
      Escherichia coli. The candidate proteins were purified, and their enzymatic
      activities were assessed. Only two proteins, encoded by the BAS5114 and BAS5304
      genes (B. anthracis Sterne designations), exhibited epimerase activity. Both
      proteins were able to convert UDP-glucose (Glc) to UDP-Gal, but only the BAS5304
      encoded protein could convert UDP-GlcNAc to UDP-GalNAc, indicating that BAS5304
      was the gene sought. Surprisingly, spores produced by a mutant strain lacking the
      BAS5304-encoded enzyme still contained normal levels of BclA-attached
      oligosaccharides. However, monosaccharide analysis of the oligosaccharides
      revealed that GlcNAc had replaced GalNAc. Thus, while GalNAc appears to be the
      preferred amino sugar for the linkage of oligosaccharides to the BclA protein
      backbone, in its absence, GlcNAc can serve as a substitute linker. Finally, we
      demonstrated that the expression of the BAS5304 gene occurred in a biphasic
      manner during both the early and late stages of sporulation.

PMID- 19749054
TI  - Identification of direct transcriptional target genes of ExoS/ChvI two-component
      signaling in Sinorhizobium meliloti.
AB  - The Sinorhizobium meliloti ExoS/ChvI two-component signaling pathway is required
      for the development of a nitrogen-fixing symbiosis between S. meliloti and its
      plant hosts. ExoS/ChvI also has important roles in regulating succinoglycan
      production, biofilm formation, motility, nutrient utilization, and the viability
      of free-living bacteria. Previous microarray experiments with an exoS96::Tn5
      mutant indicated that ExoS/ChvI influences the expression of a few hundred genes,
      complicating the investigation of which downstream genes respond directly or
      indirectly to ExoS/ChvI regulation. To focus our study of ExoS/ChvI
      transcriptional target genes, we performed transcriptional profiling with chvI
      gain-of-function and reduced-function strains. The chvI gain-of-function strain
      that we used contains a dominant gain-of-function chvI allele in addition to wild
      type chvI. We identified genes that, relative to their expression level in the
      wild type, are both upregulated in the chvI gain-of-function strain and
      downregulated in the reduced-function strain or vice versa. Guided by this
      focused set of genes, we performed gel mobility shift assays and demonstrated
      that ChvI directly binds the intergenic regions upstream of ropB1, SMb21440, and
      SMc01580. Furthermore, DNase I footprint analysis of the region upstream of
      SMc01580 identified a specific DNA sequence bound by ChvI and allowed the
      discovery of a possible motif for ChvI binding. Our results provide insight into
      the mechanism of how ExoS/ChvI regulates its downstream targets and lay a
      foundation for studying this conserved pathway with critical roles in free-living
      and symbiotic bacteria.

PMID- 19749055
TI  - Global transcriptional response to spermine, a component of the intramacrophage
      environment, reveals regulation of Francisella gene expression through insertion
      sequence elements.
AB  - Tularemia is caused by the category A biodefense agent Francisella tularensis.
      This bacterium is associated with diverse environments and a plethora of
      arthropod and mammalian hosts. How F. tularensis adapts to these different
      conditions, particularly the eukaryotic intracellular environment in which it
      replicates, is poorly understood. Here, we demonstrate that the polyamines
      spermine and spermidine are environmental signals that alter bacterial
      stimulation of host cells. Genomewide analysis showed that F. tularensis LVS
      undergoes considerable changes in gene expression in response to spermine.
      Unexpectedly, analysis of gene expression showed that multiple members of two
      classes of Francisella insertion sequence (IS) elements, ISFtu1 and ISFtu2, and
      the genes adjacent to these elements were induced by spermine. Spermine was
      sufficient to activate transcription of these IS elements and of nearby genes in
      broth culture and in macrophages. Importantly, the virulent strain of F.
      tularensis, Schu S4, exhibited similar phenotypes of cytokine induction and gene
      regulation in response to spermine. Distinctions in gene expression changes
      between Schu S4 and LVS at one orthologous locus, however, correlated with
      differences in IS element location. Our results indicate that spermine and
      spermidine are novel triggers to alert F. tularensis of its eukaryotic host
      environment. The results reported here also identify an unexpected mechanism of
      gene regulation controlled by a spermine-responsive promoter contained within IS
      elements. Different arrangements of these mobile genetic elements among
      Francisella strains may contribute to virulence by conveying new expression
      patterns for genes from different strains.

PMID- 19749056
TI  - Diminished exoproteome of Frankia spp. in culture and symbiosis.
AB  - Frankia species are the most geographically widespread gram-positive plant
      symbionts, carrying out N(2) fixation in root nodules of trees and woody shrubs
      called actinorhizal plants. Taking advantage of the sequencing of three Frankia
      genomes, proteomics techniques were used to investigate the population of
      extracellular proteins (the exoproteome) from Frankia, some of which potentially
      mediate host-microbe interactions. Initial two-dimensional sodium dodecyl sulfate
      polyacrylamide gel electrophoresis analysis of culture supernatants indicated
      that cytoplasmic proteins appeared in supernatants as cells aged, likely because
      older hyphae lyse in this slow-growing filamentous actinomycete. Using liquid
      chromatography coupled to tandem mass spectrometry to identify peptides, 38
      proteins were identified in the culture supernatant of Frankia sp. strain CcI3,
      but only three had predicted export signal peptides. In symbiotic cells, 42
      signal peptide-containing proteins were detected from strain CcI3 in Casuarina
      cunninghamiana and Casuarina glauca root nodules, while 73 and 53 putative
      secreted proteins containing signal peptides were identified from Frankia strains
      in field-collected root nodules of Alnus incana and Elaeagnus angustifolia,
      respectively. Solute-binding proteins were the most commonly identified secreted
      proteins in symbiosis, particularly those predicted to bind branched-chain amino
      acids and peptides. These direct proteomics results complement a previous
      bioinformatics study that predicted few secreted hydrolytic enzymes in the
      Frankia proteome and provide direct evidence that the symbiosis succeeds partly,
      if not largely, because of a benign relationship.

PMID- 19749057
TI  - Comparison and utilization of repetitive-element PCR techniques for typing
      Lactobacillus isolates from the chicken gastrointestinal tract.
AB  - Three repetitive-element PCR techniques were evaluated for the ability to type
      strains of Lactobacillus species commonly identified in the chicken
      gastrointestinal tract. Enterobacterial repetitive intergenic consensus PCR (ERIC
      PCR) produced species- and strain-specific profiles for Lactobacillus crispatus,
      Lactobacillus gallinarum, Lactobacillus johnsonii, and Lactobacillus reuteri
      isolates. The technique typed strains within these species equally as well as
      pulsed-field gel electrophoresis. DNA concentration and quality did not affect
      the ERIC-PCR profiles, indicating that this method, unlike other high-resolution
      methods, can be adapted to high-throughput analysis of isolates. Subsequently,
      ERIC-PCR was used to type Lactobacillus species diversity of a large collection
      of isolates derived from chickens grown under commercial and necrotic enteritis
      disease induction conditions. This study has illustrated, for the first time,
      that there is great strain diversity within each Lactobacillus species present
      and has revealed that chickens raised under commercial conditions harbor greater
      species and strain diversity than chickens raised under necrotic enteritis
      disease induction conditions.

PMID- 19749058
TI  - Effect of cinnamon oil on icaA expression and biofilm formation by Staphylococcus
      epidermidis.
AB  - Staphylococcus epidermidis is notorious for its biofilm formation on medical
      devices, and novel approaches to prevent and kill S. epidermidis biofilms are
      desired. In this study, the effect of cinnamon oil on planktonic and biofilm
      cultures of clinical S. epidermidis isolates was evaluated. Initially,
      susceptibility to cinnamon oil in planktonic cultures was compared to the
      commonly used antimicrobial agents chlorhexidine, triclosan, and gentamicin. The
      MIC of cinnamon oil, defined as the lowest concentration able to inhibit visible
      microbial growth, and the minimal bactericidal concentration, the lowest
      concentration required to kill 99.9% of the bacteria, were determined using the
      broth microdilution method and plating on agar. A checkerboard assay was used to
      evaluate the possible synergy between cinnamon oil and the other antimicrobial
      agents. The effect of cinnamon oil on biofilm growth was studied in 96-well
      plates and with confocal laser-scanning microscopy (CLSM). Biofilm susceptibility
      was determined using a metabolic 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl
      tetrazolium bromide (MTT) assay. Real-time PCR analysis was performed to
      determine the effect of sub-MIC concentrations of cinnamon oil on expression of
      the biofilm-related gene, icaA. Cinnamon oil showed antimicrobial activity
      against both planktonic and biofilm cultures of clinical S. epidermidis strains.
      There was only a small difference between planktonic and biofilm MICs, ranging
      from 0.5 to 1% and 1 to 2%, respectively. CLSM images indicated that cinnamon oil
      is able to detach and kill existing biofilms. Thus, cinnamon oil is an effective
      antimicrobial agent to combat S. epidermidis biofilms.

PMID- 19749059
TI  - Engineering of Bacillus subtilis 168 for increased nisin resistance.
AB  - Nisin is a natural bacteriocin produced commercially by Lactococcus lactis and
      widely used in the food industry as a preservative because of its broad host
      spectrum. Despite the low productivity and troublesome fermentation of L. lactis,
      no alternative cost-effective host has yet been found. Bacillus subtilis had been
      suggested as a potential host for the biosynthesis of nisin but was discarded due
      to its sensitivity to the lethal action of nisin. In this study, we have
      reevaluated the potential of B. subtilis as a host organism for the heterologous
      production of nisin. We applied transcriptome and proteome analyses of B.
      subtilis and identified eight genes upregulated in the presence of nisin. We
      demonstrated that the overexpression of some of these genes boosts the natural
      defenses of B. subtilis, which allows it to sustain higher levels of nisin in the
      medium. We also attempted to overcome the nisin sensitivity of B. subtilis by
      introducing the nisin resistance genes nisFEG and nisI from L. lactis under the
      control of a synthetic promoter library.

PMID- 19749060
TI  - Diverse enterotoxin gene profiles among clonal complexes of Staphylococcus aureus
      isolates from the Bronx, New York.
AB  - Staphylococcal enterotoxins (SE) can cause toxin-mediated disease, and those that
      function as superantigens are implicated in the pathogenesis of allergic
      diseases. The prevalence of 19 enterotoxin genes was determined by PCR in
      clinical S. aureus strains derived from wounds (108) and blood (99). We performed
      spa typing and multilocus sequence typing (MLST) to determine clonal origin, and
      for selected strains staphylococcal enterotoxin B (SEB) production was measured
      by enzyme-linked immunosorbent assay. Strains carried a median of five SE genes.
      For most SE genes, the prevalence rates among methicillin-resistant and
      methicillin-sensitive S. aureus isolates, as well as wound- and blood-derived
      isolates, did not differ. At least one SE gene was detected in all except two S.
      aureus isolates (>99%). Complete egc clusters were found in only 11% of S. aureus
      isolates, whereas the combination of sed, sej, and ser was detected in 24% of
      clinical strains. S. aureus strains exhibited distinct combinations of SE genes,
      even if their pulsed-field gel electrophoresis and MLST patterns demonstrated
      clonality. USA300 strains also showed considerable variability in SE content,
      although they contained a lower number of SE genes (mean, 3). By contrast, SE
      content was unchanged in five pairs of serial isolates. SEB production by
      individual strains varied up to 200-fold, and even up to 15-fold in a pair of
      serial isolates. In conclusion, our results illustrate the genetic diversity of
      S. aureus strains with respect to enterotoxin genes and suggest that horizontal
      transfer of mobile genetic elements encoding virulence genes occurs frequently.

PMID- 19749061
TI  - Rapid identification of Vibrio parahaemolyticus by whole-cell matrix-assisted
      laser desorption ionization-time of flight mass spectrometry.
AB  - Vibrio parahaemolyticus is a pathogenic marine bacterium that is the main
      causative agent of bacterial seafood-borne gastroenteritis in the United States.
      An increase in the frequency of V. parahaemolyticus-related infections during the
      last decade has been attributed to the emergence of an O3:K6 pandemic clone in
      1995. The diversity of the O3:K6 pandemic clone and its serovariants has been
      examined using multiple molecular techniques including multilocus sequence
      analysis, pulsed-field gel electrophoresis, and group-specific PCR analysis.
      Matrix-assisted laser desorption ionization-time of flight mass spectrometry
      (MALDI-TOF MS) has become a powerful tool for rapidly distinguishing between
      related bacterial species. In the current study, we demonstrate the development
      of a whole-cell MALDI-TOF MS method for the distinction of V. parahaemolyticus
      from other Vibrio spp. We identified 30 peaks that were present only in the
      spectra of the V. parahaemolyticus strains examined in this study that may be
      developed as MALDI-TOF MS biomarkers for identification of V. parahaemolyticus.
      We detected variation in the MALDI-TOF spectra of V. parahaemolyticus strains
      isolated from different geographical locations and at different times. The MALDI
      TOF MS spectra of the V. parahaemolyticus strains examined were distinct from
      those of the other Vibrio species examined including the closely related V.
      alginolyticus, V. harveyi, and V. campbellii. The results of this study
      demonstrate the first use of whole-cell MALDI-TOF MS analysis for the rapid
      identification of V. parahaemolyticus.

PMID- 19749062
TI  - Combination of chromogenic differential medium and estA-specific PCR for
      isolation and detection of phytopathogenic Xanthomonas spp.
AB  - A xanthomonad differential medium (designated Xan-D medium) was developed, on
      which streaks and colonies of xanthomonads, including 13 species of the genus
      Xanthomonas, turned wet-shining yellow-green and were surrounded with a smaller
      milky zone and a bigger clear zone in 3 to 4 days. The characteristics could
      easily be differentiated from those of yellow nonxanthomonads and other bacteria.
      The mechanism of color change and formation of a milky zone on the medium are
      mainly due to the Tween 80 hydrolytic capacity of xanthomonads. The gene, estA,
      responsible for Tween 80 hydrolysis was cloned and expressed in Escherichia coli,
      which acquired a capacity to hydrolyze Tween 80 and could turn green and form a
      milky zone on the Xan-D medium. The nucleotide sequence of estA is highly
      conserved in the xanthomonads, and the sequence was used to design a specific PCR
      primer set. The PCR amplification using the primer set amplified a 777-bp
      specific DNA fragment for all xanthomonad strains tested. The Xan-D medium was
      used to isolate and differentiate Xanthomonas campestris pv. campestris from
      naturally infected cabbages with black rot symptoms for a rapid diagnosis. All
      isolated X. campestris pv. campestris strains developed characteristic colonies
      and were positive in the PCR with the estA primer set. The Xan-D medium was
      further amended with antibiotics and successfully used for the detection of
      viable X. campestris pv. campestris cells from plant seeds. Although some yellow
      nonxanthomonads and other saprophytic bacteria from plant seeds could still grow
      on the medium, they did not interfere with the color development of X. campestris
      pv. campestris. However, Stenotrophomonas maltophilia, which is closely related
      to xanthomonads, existing in a seed lot could also develop yellow-green color but
      had different colony morphology and was negative in the PCR with the estA primer
      set. Accordingly, the combination of the Xan-D medium with the estA-specific PCR
      is a useful and reliable method for the isolation and detection of viable
      xanthomonad cells from plant materials.

PMID- 19749063
TI  - L-ribose production from L-arabinose by using purified L-arabinose isomerase and
      mannose-6-phosphate isomerase from Geobacillus thermodenitrificans.
AB  - Two enzymes, L-arabinose isomerase and mannose-6-phosphate isomerase, from
      Geobacillus thermodenitrificans produced 118 g/liter L-ribose from 500 g/liter L
      arabinose at pH 7.0, 70 degrees C, and 1 mM Co(2+) for 3 h, with a conversion
      yield of 23.6% and a volumetric productivity of 39.3 g liter(-1) h(-1).

PMID- 19749064
TI  - Correlation of methane production and functional gene transcriptional activity in
      a peat soil.
AB  - The transcription dynamics of subunit A of the key gene in methanogenesis (methyl
      coenzyme M reductase; mcrA) was studied to evaluate the relationship between
      process rate (methanogenesis) and gene transcription dynamics in a peat soil
      ecosystem. Soil methanogen process rates were determined during incubation of
      peat slurries at temperatures from 4 to 37 degrees C, and real-time quantitative
      PCR was applied to quantify the abundances of mcrA genes and transcripts;
      corresponding transcriptional dynamics were calculated from mcrA transcript/gene
      ratios. Internal standards suggested unbiased recovery of mRNA abundances in
      comparison to DNA levels. In comparison to those in pure-culture studies, mcrA
      transcript/gene ratios indicated underestimation by 1 order of magnitude,
      possibly due to high proportions of inactive or dead methanogens. Methane
      production rates were temperature dependent, with maxima at 25 degrees C, but
      changes in abundance and transcription of the mcrA gene showed no correlation
      with temperature. However, mcrA transcript/gene ratios correlated weakly
      (regression coefficient = 0.76) with rates of methanogenesis. Methanogen process
      rates increased over 3 orders of magnitude, while the corresponding maximum
      transcript/gene ratio increase was only 18-fold. mcrA transcript dynamics
      suggested steady-state expression in peat soil after incubation for 24 and 48 h,
      similar to that in stationary-phase cultures. mcrA transcript/gene ratios are
      therefore potential in situ indicators of methanogen process rate changes in
      complex soil systems.

PMID- 19749065
TI  - Dominant bacteria and biomass in the Kuytun 51 Glacier.
AB  - Dominant bacteria in the different habitats in the Kuytun 51 Glacier were
      investigated using a 16S rRNA gene clone library sequencing technique. Results
      showed diverse bacteria on the glacial surface, with the dominant phyla being
      Proteobacteria, Cyanobacteria, and Bacteroidetes. UniFrac data showed distinct
      community patterns between the Kuytun and Himalayan Rongbuk glaciers.

PMID- 19749066
TI  - Statistical assessment of variability of terminal restriction fragment length
      polymorphism analysis applied to complex microbial communities.
AB  - The variability of terminal restriction fragment polymorphism analysis applied to
      complex microbial communities was assessed statistically. Recent technological
      improvements were implemented in the successive steps of the procedure, resulting
      in a standardized procedure which provided a high level of reproducibility.

PMID- 19749067
TI  - Cryptosporidium propidium monoazide-PCR, a molecular biology-based technique for
      genotyping of viable Cryptosporidium oocysts.
AB  - Cryptosporidium is an important waterborne protozoan parasite that can cause
      severe diarrhea and death in the immunocompromised. The current methods used to
      monitor for Cryptosporidium oocysts in water are the microscopy-based USEPA
      methods 1622 and 1623. These methods assess total levels of oocysts in source
      waters, but do not determine oocyst viability or genotype. Recently, propidium
      monoazide (PMA) has been used in conjunction with molecular diagnostic tools to
      identify species and assess the viability of bacteria. The goal of this study was
      the development of a Cryptosporidium PMA-PCR (CryptoPMA-PCR) assay that includes
      PMA treatment prior to PCR analysis in order to prevent the amplification of DNA
      from dead oocysts. The results demonstrated that PMA penetrates only dead oocysts
      and blocks amplification of their DNA. The CryptoPMA-PCR assay can also
      specifically detect live oocysts within a mixed population of live and dead
      oocysts. More importantly, live oocysts, not dead oocysts, were detected in raw
      waste or surface water samples spiked with Cryptosporidium oocysts. This proof-of
      concept study is the first to demonstrate the use of PMA for pre-PCR treatment of
      Cryptosporidium oocysts. The CryptoPMA-PCR assay is an attractive approach to
      specifically detect and genotype viable Cryptosporidium oocysts in the water,
      which is critical for human health risk assessment.

PMID- 19749068
TI  - Edwardsiella ictaluri encodes an acid-activated urease that is required for
      intracellular replication in channel catfish (Ictalurus punctatus) macrophages.
AB  - Genomic analysis indicated that Edwardsiella ictaluri encodes a putative urease
      pathogenicity island containing the products of nine open reading frames,
      including urea and ammonium transporters. In vitro studies with wild-type E.
      ictaluri and a ureG::kan urease mutant strain indicated that E. ictaluri is
      significantly tolerant of acid conditions (pH 3.0) but that urease activity is
      not required for acid tolerance. Growth studies demonstrated that E. ictaluri is
      unable to grow at pH 5 in the absence of urea but is able to elevate the
      environmental pH from pH 5 to pH 7 and grow when exogenous urea is available.
      Substantial production of ammonia was observed for wild-type E. ictaluri in vitro
      in the presence of urea at low pH, and optimal activity occurred at pH 2 to 3. No
      ammonia production was detected for the urease mutant. Proteomic analysis with
      two-dimensional gel electrophoresis indicated that urease proteins are expressed
      at both pH 5 and pH 7, although urease activity is detectable only at pH 5.
      Urease was not required for initial invasion of catfish but was required for
      subsequent proliferation and virulence. Urease was not required for initial
      uptake or survival in head kidney-derived macrophages but was required for
      intracellular replication. Intracellular replication of wild-type E. ictaluri was
      significantly enhanced when urea was present, indicating that urease plays an
      important role in intracellular survival and replication, possibly through
      neutralization of the acidic environment of the phagosome.

PMID- 19749069
TI  - Dehalogenation activities and distribution of reductive dehalogenase homologous
      genes in marine subsurface sediments.
AB  - Halogenated organic compounds serve as terminal electron acceptors for anaerobic
      respiration in a diverse range of microorganisms. Here, we report on the
      widespread distribution and diversity of reductive dehalogenase homologous (rdhA)
      genes in marine subsurface sediments. A total of 32 putative rdhA phylotypes were
      detected in sediments from the southeast Pacific off Peru, the eastern equatorial
      Pacific, the Juan de Fuca Ridge flank off Oregon, and the northwest Pacific off
      Japan, collected at a maximum depth of 358 m below the seafloor. In addition,
      significant dehalogenation activity involving 2,4,6-tribromophenol and
      trichloroethene was observed in sediment slurry from the Nankai Trough Forearc
      Basin. These results suggest that dehalorespiration is an important energy
      yielding pathway in the subseafloor microbial ecosystem.

PMID- 19749070
TI  - Pathotype and antibiotic resistance gene distributions of Escherichia coli
      isolates from broiler chickens raised on antimicrobial-supplemented diets.
AB  - The impact of feed supplementation with bambermycin, monensin, narasin,
      virginiamycin, chlortetracycline, penicillin, salinomycin, and bacitracin on the
      distribution of Escherichia coli pathotypes in broiler chickens was investigated
      using an E. coli virulence DNA microarray. Among 256 E. coli isolates examined,
      59 (23%) were classified as potentially extraintestinal pathogenic E. coli
      (ExPEC), while 197 (77%) were considered commensal. Except for chlortetracycline
      treatment, the pathotype distribution was not significantly different among
      treatments (P > 0.05). Within the 59 ExPEC isolates, 44 (75%) were determined to
      be potentially avian pathogenic E. coli (APEC), with the remaining 15 (25%)
      considered potentially "other" ExPEC isolates. The distribution within
      phylogenetic groups showed that 52 (88%) of the ExPEC isolates belonged to groups
      B2 and D, with the majority of APEC isolates classified as group D and most
      commensal isolates (170, 86%) as group A or B1. Indirect assessment of the
      presence of the virulence plasmid pAPEC-O2-ColV showed a strong association of
      the plasmid with APEC isolates. Among the 256 isolates, 224 (88%) possessed at
      least one antimicrobial resistance gene, with nearly half (107, 42%) showing
      multiple resistance genes. The majority of resistance genes were distributed
      among commensal isolates. Considering that the simultaneous detection of
      antimicrobial resistance tet(A), sulI, and bla(TEM) genes and the integron class
      I indicated a potential presence of the resistance pAPEC-O2-R plasmid, the
      results revealed that 35 (14%) of the isolates, all commensals, possessed this
      multigene resistance plasmid. The virulence plasmid was never found in
      combination with the antimicrobial resistance plasmid. The presence of the ColV
      plasmid or the combination of iss and tsh genes in the majority of APEC isolates
      supports the notion that when found together, the plasmid, iss, and tsh serve as
      good markers for APEC. These data indicate that different resistant E. coli
      pathotypes can be found in broiler chickens and that the distribution of such
      pathotypes and certain virulence determinants could be modulated by antimicrobial
      agent feed supplementation.

PMID- 19749071
TI  - Microhabitats within venomous cone snails contain diverse actinobacteria.
AB  - Actinomycetes can be symbionts in diverse organisms, including both plants and
      animals. Some actinomycetes benefit their host by producing small molecule
      secondary metabolites; the resulting symbioses are often developmentally complex.
      Actinomycetes associated with three cone snails were studied. Cone snails are
      venomous tropical marine gastropods which have been extensively examined because
      of their production of peptide-based neurological toxins, but no microbiological
      studies have been reported on these organisms. A microhabitat approach was used
      in which dissected tissue from each snail was treated as an individual sample in
      order to explore bacteria in the tissues separately. Our results revealed a
      diverse, novel, and highly culturable cone snail-associated actinomycete
      community, with some isolates showing promising bioactivity in a neurological
      assay. This suggests that cone snails may represent an underexplored reservoir of
      novel actinomycetes of potential interest for drug discovery.

PMID- 19749072
TI  - Insufficiency of copper ion homeostasis causes freeze-thaw injury of yeast cells
      as revealed by indirect gene expression analysis.
AB  - Saccharomyces cerevisiae is exposed to freeze-thaw stress in commercial
      processes, including frozen dough baking. Cell viability and fermentation
      activity after a freeze-thaw cycle were dramatically decreased due to freeze-thaw
      injury. Because this type of injury involves complex phenomena, the injury
      mechanisms are not fully understood. We examined freeze-thaw injury by indirect
      gene expression analysis during postthaw incubation after freeze-thaw treatment
      using DNA microarray profiling. The results showed that genes involved in the
      homeostasis of metal ions were frequently contained in genes that were
      upregulated, depending on the freezing period. We assessed the phenotype of
      deletion mutants of the metal ion homeostasis genes that exhibited freezing
      period-dependent upregulation and found that the strains with deletion of the
      MAC1 and CTR1 genes involved in copper ion homeostasis exhibited freeze-thaw
      sensitivity, suggesting that copper ion homeostasis is required for freeze-thaw
      tolerance. We found that supplementation with copper ions during postthaw
      incubation increased intracellular superoxide dismutase activity and
      intracellular levels of reactive oxygen species were decreased. Moreover, cell
      viability was increased by supplementation with copper ions. These results
      suggest that insufficiency of copper ion homeostasis may be one of the causes of
      freeze-thaw injury.

PMID- 19749073
TI  - Composition and activity of an autotrophic Fe(II)-oxidizing, nitrate-reducing
      enrichment culture.
AB  - 16S rRNA gene libraries from the lithoautotrophic Fe(II)-oxidizing, nitrate
      reducing enrichment culture described by Straub et al. (K. L. Straub, M. Benz, B.
      Schink, and F. Widdel, Appl. Environ. Microbiol. 62:1458-1460, 1996) were
      dominated by a phylotype related (95% 16S rRNA gene homology) to the autotrophic
      Fe(II) oxidizer Sideroxydans lithotrophicus. The libraries also contained
      phylotypes related to known heterotrophic nitrate reducers Comamonas badia,
      Parvibaculum lavamentivorans, and Rhodanobacter thiooxidans. The three
      heterotrophs were isolated and found to be capable of only partial (12 to 24%)
      Fe(II) oxidation, suggesting that the Sideroxydans species has primary
      responsibility for Fe(II) oxidation in the enrichment culture.

PMID- 19749074
TI  - Atypical meningeal involvement in Wegener granulomatosis: MR imaging survey of a
      particular case.

PMID- 19749076
TI  - Collaboration between the Journals Interventional Neuroradiology and American
      Journal of Neuroradiology.

PMID- 19749077
TI  - Vertigo and hearing loss.

PMID- 19749078
TI  - Some challenges facing Lean Thinking in healthcare.

PMID- 19749079
TI  - Pharmacological characterization of 3-[3-tert-butylsulfanyl-1-[4-(6-methoxy
      pyridin-3-yl)-benzyl]-5-(pyridin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethyl
      propionic acid (AM103), a novel selective 5-lipoxygenase-activating protein
      inhibitor that reduces acute and chronic inflammation.
AB  - Leukotrienes (LTs) are proinflammatory lipid mediators synthesized by the
      conversion of arachidonic acid (AA) to LTA(4) by the enzyme 5-lipoxygenase (5-LO)
      in the presence of 5-LO-activating protein (FLAP). 3-[3-tert-Butylsulfanyl-1-[4
      (6-methoxy-pyridin-3-yl)-benzyl]-5-(pyridin-2-ylmethoxy)-1H-indol-2-yl]-2,2
      dimethyl-propionic acid (AM103) is a novel selective FLAP inhibitor in
      development for the treatment of respiratory conditions such as asthma. In a rat
      ex vivo whole-blood calcium ionophore-induced LTB(4) assay, AM103 (administered
      orally at 1 mg/kg) displayed >50% inhibition for up to 6 h with a calculated
      EC(50) of approximately 60 nM. When rat lung was challenged in vivo with calcium
      ionophore, AM103 inhibited LTB(4) and cysteinyl leukotriene (CysLT) production
      with ED(50) values of 0.8 and 1 mg/kg, respectively. In this model, the EC(50)
      derived from plasma AM103 was approximately 330 nM for inhibition of both LTB(4)
      and CysLT. In an acute inflammation setting, AM103 displayed dose-dependent
      inhibition of LTB(4), CysLT, and plasma protein extravasation induced by
      peritoneal zymosan injection. In a model of chronic lung inflammation using
      ovalbumin-primed and challenged BALB/c mice, AM103 reduced the concentrations of
      eosinophil peroxidase, CysLTs, and interleukin-5 in the bronchoalveolar lavage
      fluid. Finally, AM103 increased survival time in mice exposed to a lethal
      intravenous injection of platelet-activating factor. In summary, AM103 is a
      novel, potent and selective FLAP inhibitor that has excellent pharmacodynamic
      properties in vivo and is effective in animal models of acute and chronic
      inflammation and in a model of lethal shock.

PMID- 19749080
TI  - Adenosine suppresses lipopolysaccharide-induced tumor necrosis factor-alpha
      production by murine macrophages through a protein kinase A- and exchange protein
      activated by cAMP-independent signaling pathway.
AB  - Adenosine is generated during tissue hypoxia and stress, which reduces
      inflammation by suppressing the activity of most immune cells. Among its various
      actions, adenosine suppresses the production of proinflammatory cytokines
      including tumor necrosis factor (TNF)-alpha, through the cAMP-elevating A(2A)
      adenosine receptor (AR) subtype. In this study, we examined the signaling
      mechanisms by which A(2A)AR activation inhibits TNF-alpha production in
      thioglycollate-elicited mouse peritoneal macrophages. Pretreating murine
      macrophages with the nonselective AR agonist adenosine-5'-N-ethylcarboxamide
      (NECA), the A(2A)AR agonist 2-[p-(2-carboxyethyl)phenethylamino]-5'-N
      ethylcarboxamidoadenosine (CGS 21680), or the cAMP-elevating agent forskolin
      reduced TNF-alpha production in response to lipopolysaccharide (LPS) by greater
      than 60%. All of these agents increased cAMP production in macrophages and
      activated protein kinase A (PKA). However, we were surprised to find that
      treating macrophages with three different PKA inhibitors or small interfering RNA
      mediated knockdown of the exchange protein activated by cAMP (Epac-1) failed to
      block the suppressive actions of NECA or forskolin on LPS-induced TNF-alpha
      release. Instead, okadaic acid was effective at low concentrations that
      selectively inhibit protein serine/threonine phosphatases. Subsequent studies
      showed that NECA and forskolin decreased LPS-induced steady-state TNF-alpha mRNA
      levels; this effect was due to a decreased rate of transcription based on assays
      examining the rate of generation of primary TNF-alpha transcripts. Treatment with
      NECA or forskolin did not interfere with LPS-induced translocation or DNA binding
      of the RelA/p65 subunit of nuclear factor-kappaB or phosphorylation of inhibitor
      of nuclear factor-kappaB-alpha, extracellular signal-regulated kinase 1/2, c-Jun
      NH(2)-terminal kinase, or p38 kinase. Our results suggest that AR activation
      inhibits LPS-induced TNF-alpha production by murine macrophages at the level of
      gene transcription through a unique cAMP-dependent, but PKA- and Epac
      independent, signaling pathway involving protein phosphatase activity.

PMID- 19749081
TI  - Involvement of cyclooxygenase-2 in carbachol-induced positive inotropic response
      in mouse isolated left atrium.
AB  - The mouse heart is expected to have characteristic contractile properties.
      However, basic information on the function of the mouse heart has not been
      accumulated sufficiently. In this study, the involvement of cyclooxygenase (COX)
      2 in carbachol (CCh)-induced inotropic response was investigated in mouse
      isolated left atrium. Influences of CCh and their mechanisms of action on
      developed tension elicited by electrical stimulation were examined
      pharmacologically. The presence of COX-2 in atrium was examined by Western
      blotting and immunohistochemical analysis. CCh (3 microM for 15 min) produced a
      biphasic inotropic response: a transient decrease in contractile force followed
      by a late increase. Atropine suppressed the biphasic inotropic response to CCh. A
      muscarinic M(3) receptor antagonist, 4-diphenyl-acetoxy-N-methlpiperidine,
      inhibited the late positive inotropic action. Blockade of prostaglandin (PG) E(2)
      or F(2alpha) receptor by 6-isopropoxy-9-oxoxanthene-2-carboxylic acid (AH6809) or
      9alpha, 15R-dihydroxy-11beta-fluoro-15-(2,3-dihydro-1H-inden-2-yl)-16,17,18,19,20
      pentanor-prosta 5Z, 13E-dien-1-oic acid (AL8810), respectively, significantly
      suppressed the positive inotropic response to CCh. A nonselective COX inhibitor,
      indomethacin, and a selective COX-2 inhibitor, N-[2-(cyclohexyloxy)-4
      nitrophenyl]-methanesulfonamide (NS-398) inhibited the positive response. A COX-1
      inhibitor, valeroyl salicylate, did not affect the positive response. The
      positive response was almost completely abolished in the endocardial endothelium
      deprived atria. Existence of COX-2 in endocardial endothelium was confirmed by
      Western blotting and immunohistochemical analysis. The present study indicated
      that the CCh-induced positive inotropic response was mediated by PGs, possibly
      PGE(2) and PGF(2alpha), released in part from endocardial endothelium.
      Furthermore, for the first time, we demonstrated that the production of PGs
      depended in part on COX-2 in endocardial endothelium through the muscarinic M(3)
      receptor stimulation.

PMID- 19749086
TI  - Promoting elementary physical education: results of a school-based evaluation
      study.
AB  - Using a quasiexperimental design, the authors examine whether fourth- and fifth
      grade students exposed to a developmental physical education (PE) curriculum,
      Michigan's Exemplary Physical Education Curriculum (EPEC), demonstrated stronger
      motor skill-specific self-efficacy and perceptions of physical activity
      competence, physical activity levels, motor skills, and physical fitness than did
      students exposed to existing PE curricula. The authors conducted a multilevel
      regression analysis with data from 1,464 students in the fourth and fifth grades.
      Data were collected using a student survey, an activity checklist, and motor and
      fitness assessments. Compared to students receiving standard PE, students exposed
      to EPEC showed significantly stronger results in motor skills but not fitness
      outcomes. The authors found significant positive intervention effects on
      indicators of motor skill self-efficacy and physical activity levels among the
      fourth-grade cohort. EPEC was more effective than standard PE curricula at
      improving motor skill performance (fourth- and fifth-grade cohorts) and at
      increasing self-reported motor skill-specific self-efficacy and physical activity
      (fourth-grade cohort).

PMID- 19749087
TI  - Disseminating chronic disease prevention "to or with" Canadian public health
      systems.
AB  - This article follows a conceptual article published in this journal by Elliott et
      al. and provides an empirical evaluation of the Canadian Heart Health Initiative
      Dissemination Phase. Between 1994 and 2005, seven provincial research teams of
      the Canadian Heart Health Initiative-Dissemination Phase undertook projects to
      disseminate and evaluate the uptake of evidence-based chronic disease prevention
      strategies in their respective health systems. In this study, the authors draw
      from document and stakeholder interview analyses to assess the influence of
      strategic decisions about dissemination objects, targets, activities, and
      relationships between knowledge producers and users on the outcomes of chronic
      disease prevention programming. The findings show that successful dissemination
      strategies are not necessarily contingent on a high level of fidelity across
      these dimensions but depend more on the extent to which they are responsive to
      contextual variables within highly dynamic health systems.

PMID- 19749088
TI  - P2X7 receptor activates multiple selective dye-permeation pathways in RAW 264.7
      and human embryonic kidney 293 cells.
AB  - P2X7 receptor has gained an increasing importance as a drug target. One important
      response to P2X7 receptor stimulation is the uptake of large molecular weight
      tracers into cells. However, mechanism for this response is not understood
      clearly, but it is generally believed that a nonselective large pore protein
      forms this P2X7 receptor-activated permeability pathway. We examined human
      embryonic kidney (HEK) 293 cells transfected with rat P2X7 receptors (HEK-rP2X7)
      and a macrophage derived cell line, RAW 264.7, that expresses an endogenous P2X7
      receptor. We used confocal microscopy to investigate uptake of different types of
      dyes into these cells after ATP application. Stimulation of P2X7 receptors in HEK
      rP2X7 cells activated two different dye uptake pathways. The first was permeable
      to the cationic fluorescent dyes YO-PRO-1 and TO-TO-1 but not to the anionic dyes
      lucifer yellow and calcein and did not require intracellular Ca2+ concentration
      ([Ca2+](i)) increase to be activated. The second pathway permeated only lucifer
      yellow and was completely dependent on [Ca2+](i) for activation. In RAW 264.7
      cells, P2X7 receptor stimulation activated uptake of ethidium, YO-PRO-1, TO-TO-1,
      lucifer yellow, and calcein. Again, two different permeation pathways were
      discerned in RAW 264.7 cells: one permeated only ethidium and the other one, only
      lucifer yellow. We did observed no clear [Ca2+](i) dependence for these
      permeation pathways. Our results demonstrate that instead of a single
      nonselective pore, P2X7 receptor seems to activate at least two permeation
      pathways, one for cationic and one for anionic dyes with different activation
      properties.

PMID- 19749089
TI  - Working memory, strategy knowledge, and strategy instruction in children with
      reading disabilities.
AB  - Two experiments investigated the effects of strategy knowledge and strategy
      training on the working memory (WM) performance in children (ages 10-11) with and
      without reading disabilities (RD). Experiment 1 examined the relationship between
      strategy knowledge (stability of strategy choices) and WM performance as a
      function of initial, gain (cued), and maintenance conditions. WM performance was
      significantly improved for both groups under cued conditions; however, the
      performances of children with RD were inferior to those of children without RD
      across all memory conditions. Measures of WM capacity rather than strategy
      stability or processing efficiency best predicted reading comprehension
      performance. Experiment 2 assessed the effects of strategy training on WM
      performance by randomly assigning children to strategy instruction or control
      conditions. Significant improvements in WM performance occurred as a function of
      training conditions, but the residual WM differences between the reading groups
      remained. Although the results showed that stable strategy choices, cued
      performance, and strategy instruction significantly bolstered WM performance in
      children with RD, their overall WM performance, however, was constrained by
      capacity limitations.

PMID- 19749090
TI  - Uptake of CCR7 and acquisition of migratory properties by human KIR+ NK cells
      interacting with monocyte-derived DC or EBV cell lines: regulation by KIR/HLA
      class I interaction.
AB  - C-C chemokine receptor type 7 (CCR7) is a chemokine receptor playing a pivotal
      role in the induction of human natural killer (NK)-cell migration to lymph nodes.
      We show that "licensed" peripheral blood killer immunoglobulin-like receptor
      positive (KIR(+)) NK-cell populations, as well as KIR(+) NK-cell clones, de novo
      express CCR7 upon coculture with mature dendritic cells (mDCs) or Epstein-Barr
      virus (EBV)-transformed lymphoblastoid cell lines. As a consequence, they become
      capable of migrating in response to the CCR7-specific chemokines C-C chemokine
      ligand (CCL)-19 and/or CCL21. The acquisition of CCR7 by NK cells requires direct
      cell-to-cell contact, is detectable within a few minutes, and is due to receptor
      uptake from CCR7(+) cells. This mechanism is tightly regulated by KIR-mediated
      recognition of human leukocyte antigen (HLA) class I as well as by adhesion
      molecules including leukocyte function-associated antigen 1 (LFA-1) and CD2.
      Analysis of NK-cell clones revealed that alloreactive (KIR-ligand mismatched) but
      not autologous NK cells acquire CCR7. These data have important implications in
      haploidentical hematopoietic stem cell transplantation (HSCT), in which
      alloreactive NK cells may acquire the ability to migrate to secondary lymphoid
      compartments (SLCs), where they can kill recipient antigen-presenting cells
      (APCs) and T cells thus preventing graft-versus-host (and host-versus-graft)
      reactions.

PMID- 19749091
TI  - Vaccine site inflammation potentiates idiotype DNA vaccine-induced therapeutic T
      cell-, and not B cell-, dependent antilymphoma immunity.
AB  - Lymphoma idiotype protein vaccines have shown therapeutic potential in previous
      clinical studies, and results from a completed pivotal, phase 3 controlled trial
      are promising. However, streamlined production of these patient-specific vaccines
      is required for eventual clinical application. Here, we show that second
      generation, chemokine-fused idiotype DNA vaccines, when combined with myotoxins
      that induced sterile inflammation with recruitment of antigen-presenting cells at
      vaccination sites, were exceptional in their ability to provoke memory antitumor
      immunity in mice, compared with several TLR agonists. The combined vaccination
      strategy elicited both antigen-specific T-cell responses and humoral immunity.
      Unexpectedly, vaccine-induced tumor protection was intact in B cell-deficient
      mice but was abrogated completely by T-cell depletion in vivo, suggesting T-cell
      dependence. Furthermore, the optimal effect of myotoxins was observed with fusion
      vaccines that specifically targeted antigen delivery to antigen-presenting cells
      and not with vaccines lacking a targeting moiety, suggesting that the rational
      vaccine design will require combination strategies with novel, proinflammatory
      agents and highly optimized molecular vaccine constructs. These studies also
      challenge the paradigm that antibody responses are the primary of idiotype
      specific antitumor effects and support the optimization of idiotype vaccines
      designed to induce primarily T-cell immunity.

PMID- 19749092
TI  - Spatial gradients of blood vessels and hematopoietic stem and progenitor cells
      within the marrow cavities of the human skeleton.
AB  - This report evaluates the spatial profile of blood vessel fragments (BVFs) and
      CD34(+) and CD117(+) hematopoietic stem and progenitor cells (HSPCs) in human
      cancellous bone. Bone specimens were sectioned, immunostained (anti-CD34 and anti
      CD117), and digitally imaged. Immunoreactive cells and vessels were then
      optically and morphometrically identified and labeled on the corresponding
      digital image. The distance of each BVF, or CD34(+) or CD117(+) HSPC to the
      nearest trabecular surface was measured and binned in 50-microm increments. The
      relative concentration of HSPCs and BVFs within cancellous marrow was observed to
      diminish with increasing distance in the marrow space. On average, 50% of the
      CD34(+) HSPC population, 60% of the CD117(+) HSPC population, and 72% of the BVFs
      were found within 100 microm of the bone surfaces. HSPCs were also found to exist
      in close proximity to BVFs, which supports the notion of a shared HSPC and vessel
      spatial niche.

PMID- 19749093
TI  - miR-128b is a potent glucocorticoid sensitizer in MLL-AF4 acute lymphocytic
      leukemia cells and exerts cooperative effects with miR-221.
AB  - MLL-AF4 acute lymphocytic leukemia (ALL) has a poor prognosis. MicroRNAs (miRNA)
      are small noncoding RNAs that posttranscriptionally regulate expression of target
      mRNAs. Our analysis of previously published data showed that expression of miR
      128b and miR-221 is down-regulated in MLL-rearranged ALL relative to other types
      of ALL. Reexpression of these miRNAs cooperatively sensitizes 2 cultured lines of
      MLL-AF4 ALL cells to glucocorticoids. Target genes down-regulated by miR-128b
      include MLL, AF4, and both MLL-AF4 and AF4-MLL fusion genes; miR-221 down
      regulates CDKN1B. These results demonstrate that down-regulation of miR-128b and
      miR-221 is implicated in glucocorticoid resistance and that restoration of their
      levels is a potentially promising therapeutic in MLL-AF4 ALL.

PMID- 19749094
TI  - The role of B cells in the pathogenesis of graft-versus-host disease.
AB  - Allogeneic hematopoietic stem cell transplantation is an established treatment
      modality for malignant and nonmalignant hematologic diseases. Acute and chronic
      graft-versus-host diseases (GVHDs) are a major cause of morbidity and mortality
      after allogeneic stem cell transplantation. T cells have been identified as key
      players in the graft-versus-host reaction and, therefore, most established drugs
      used against GVHD target T cells. Despite our knowledge on the pathogenesis of
      the GVH reaction, success of established therapies for prevention and treatment
      of GHVD is unsatisfactory. Recently, animal and human studies demonstrated that B
      cells are involved in the immunopathophysiology of acute and chronic GVHD. Early
      phase clinical trials of B-cell depletion with rituximab have shown beneficial
      effects on both acute and chronic GVHD. This review summarizes the current
      experimental and clinical evidence for the involvement of B cells in the
      pathogenesis of acute and chronic GVHD and discusses the clinical implications
      for the management of patients undergoing allogeneic stem cell transplantation.

PMID- 19749095
TI  - Functional consequences of structural differences in stingray sensory systems.
      Part I: mechanosensory lateral line canals.
AB  - Short range hydrodynamic and electrosensory signals are important during final
      stages of prey capture in elasmobranchs (sharks, skates and rays), and may be
      particularly useful for dorso-ventrally flattened batoids with mouths hidden from
      their eyes. In stingrays, both the lateral line canal and electrosensory systems
      are highly modified and complex with significant differences on ventral surfaces
      that relate to feeding ecology. This study tests functional hypotheses based on
      quantified differences in sensory system morphology of three stingray species,
      Urobatis halleri, Myliobatis californica and Pteroplatytrygon violacea. Part I
      investigates the mechanosensory lateral line canal system whereas part II focuses
      on the electrosensory system. Stingray lateral line canals include both pored and
      non-pored sections and differ in branching complexity and distribution. A greater
      proportion of pored canals and high pore numbers were predicted to correspond to
      increased response to water flow. Behavioral experiments were performed to
      compare responses of stingrays to weak water jets mimicking signals produced by
      potential prey at velocities of 10-20 cm s(-1). Bat rays, M. californica, have
      the most complex and broadly distributed pored canal network and demonstrated
      both the highest response rate and greater response intensity to water jet
      signals. Results suggest that U. halleri and P. violacea may rely on additional
      sensory input, including tactile and visual cues, respectively, to initiate
      stronger feeding responses. These results suggest that stingray lateral line
      canal morphology can indicate detection capabilities through responsiveness to
      weak water jets.

PMID- 19749096
TI  - Functional consequences of structural differences in stingray sensory systems.
      Part II: electrosensory system.
AB  - Elasmobranch fishes (sharks, skates and rays) possess highly sensitive
      electrosensory systems, which enable them to detect weak electric fields such as
      those produced by potential prey organisms. Different species have unique
      electrosensory pore numbers, densities and distributions. Functional differences
      in detection capabilities resulting from these structural differences are largely
      unknown. Stingrays and other batoid fishes have eyes positioned on the opposite
      side of the body from the mouth. Furthermore, they often feed on buried prey,
      which can be located non-visually using the electrosensory system. In the present
      study we test functional predictions based on structural differences in three
      stingray species (Urobatis halleri, Pteroplatytrygon violacea and Myliobatis
      californica) with differing electrosensory system morphology. We compare
      detection capabilities based upon behavioral responses to dipole electric signals
      (5.3-9.6 microA). Species with greater ventral pore numbers and densities were
      predicted to demonstrate enhanced electrosensory capabilities. Electric field
      intensities at orientation were similar among these species, although they
      differed in response type and orientation pathway. Minimum voltage gradients
      eliciting feeding responses were well below 1 nVcm(-1) for all species regardless
      of pore number and density.

PMID- 19749097
TI  - Effects of temperature and dietary sterol availability on growth and cholesterol
      allocation of the aquatic keystone species Daphnia.
AB  - Enhanced water temperatures promote the occurrence of cyanobacterial blooms,
      which may be detrimental to aquatic herbivores. Especially, the often-dominant
      crustaceans could be negatively affected because cyanobacteria are deficient in
      phytosterols, which are required by the crustaceans to form the membrane
      component cholesterol, which in turn plays a role in thermal adaptation. Here, we
      determined the influence of temperature on growth, reproduction and the
      allocation of dietary sterol into somatic tissues and eggs of the keystone
      species Daphnia magna raised along a dietary cholesterol gradient. Mass-specific
      growth rates of D. magna increased with the increasing availability of dietary
      cholesterol up to an incipient limiting level, which increased with increasing
      temperature. This indicates a higher demand for cholesterol for growth at higher
      temperatures and may explain the consistently smaller clutch sizes of reproducing
      females at the highest temperature. The cholesterol content of the individuals
      increased with increasing dietary cholesterol; this increase was enhanced at
      higher temperatures, indicating a higher demand for cholesterol for tissues and
      probably specifically for membranes. Surprisingly, the daphnids showed different
      allocation strategies with regard to temperature and dietary sterol availability.
      The cholesterol content of eggs was enhanced at higher temperature, which
      suggested that females allocate more cholesterol to their offspring, presumably
      to ensure sufficient egg development. When dietary cholesterol was limiting,
      however, females did not allocate more cholesterol to their eggs. Our data
      suggest that during cyanobacterial blooms, a potential dietary sterol limitation
      of Daphnia can be intensified at higher water temperatures, which can occur with
      global warming.

PMID- 19749098
TI  - Food restriction in young Japanese quails: effects on growth, metabolism, plasma
      thyroid hormones and mRNA species in the thyroid hormone signalling pathway.
AB  - Young birds, in their post-natal growth period, may reduce their growth and
      metabolism when facing a food shortage. To examine how such responses can be
      mediated by endocrine-related factors, we exposed Japanese quail chicks to food
      restriction for either 2 days (age 6-8 days) or 5 days (age 6-11 days). We then
      measured growth and resting metabolic rate (RMR), and circulating 3,3',5-triiodo
      l-thyronine (T3) and 3,5,3',5'-tetraiodothyronine (T4) levels as well as
      expression patterns of genes involved in growth (insulin-like growth factor-I:
      IGF-I) and thyroid hormone signalling (thyroid-stimulating hormone-beta: TSHbeta,
      type II iodothyronine deiodinase: D2, thyroid hormone receptors isoforms: TRalpha
      and TRbeta). The food-restricted chicks receiving a weight-maintenance diet
      showed reductions in structural growth and RMR. Plasma levels of both T3 and T4
      were reduced in the food-restricted birds, and within the 5 days food-restricted
      group there was a positive correlation between RMR and T3. IGF-I mRNA showed
      significantly higher abundance in the liver of ad libitum fed birds at day 8
      compared with food-restricted birds. In the brain, TSHbeta mRNA level tended to
      be lower in food-restricted quails on day 8 compared with controls. Furthermore,
      TRalpha expression was lower in the brain of food-restricted birds at day 8
      compared with birds fed ad libitum. Interestingly, brain D2 mRNA was negatively
      correlated with plasma T3 levels, tending to increase with the length of food
      restriction. Overall, our results show that food restriction produced significant
      effects on circulating thyroid hormones and differentially affected mRNA species
      in the thyroid hormone signalling pathway. Thus, we conclude that the effects of
      food restriction observed on growth and metabolism were partly mediated by
      changes in the endocrine-related factors investigated.

PMID- 19749099
TI  - Heterothermy in small, migrating passerine birds during stopover: use of
      hypothermia at rest accelerates fuel accumulation.
AB  - For small endothermic animals, heterothermy serves as an energy-saving mechanism
      for survival in challenging environments, but it may also accelerate fat
      accumulation in individuals preparing for fuel-demanding activities. This is the
      first study to demonstrate adaptive hypothermic responses in migrating
      passerines. While monitoring body temperature (T(b)) of eight blackcaps (Sylvia
      atricapilla) by radiotelemetry, we found that during daytime T(b)=42.5+/-0.4
      degrees C (mean +/- s.d.); at night T(b) decreased to a minimum between 33 and 40
      degrees C. We determined the lower limit for normothermy at 37.4 degrees C and
      found that on 12 out of 34 bird-nights of observations under semi-natural
      conditions blackcaps reduced their T(b) below normothermic resting levels with
      minimum values of 33 and 34.5 degrees C compared with rest-phase normothermic
      T(b) of 38.8+/-0.8 degrees C. In birds of body mass (m(b)) <16.3 g, minimum T(b)
      at night correlated with the individual's m(b) (r=0.67, P<0.01, N=17), but this
      was not the case in birds with m(b)>16.3 g. Minimum nocturnal T(b) did not
      correlate with night-time air temperature (T(a)). Measurements of metabolic rate
      in birds subjected to a T(a) of 15 degrees C showed that hypothermia of this
      magnitude can lead to a reduction of some 30% in energy expenditure compared with
      birds remaining normothermic. Our data suggest that by reducing the T(b)-T(a)
      gradient, blackcaps accelerate their rate of fuel accumulation at a stopover.
      When body energy reserves are low blackcaps may achieve this reduction by
      entering hypothermia. Since hypothermia, as seen in blackcaps, may lead to
      significant energy savings and facilitate body mass gain, we predict that it is
      common among small migrating passerines.

PMID- 19749100
TI  - Flexible clap and fling in tiny insect flight.
AB  - Of the insects that have been filmed in flight, those that are 1 mm in length or
      less often clap their wings together at the end of each upstroke and fling them
      apart at the beginning of each downstroke. This ;clap and fling' motion is
      thought to augment the lift forces generated during flight. What has not been
      highlighted in previous work is that very large forces are required to clap the
      wings together and to fling the wings apart at the low Reynolds numbers relevant
      to these tiny insects. In this paper, we use the immersed boundary method to
      simulate clap and fling in rigid and flexible wings. We find that the drag forces
      generated during fling with rigid wings can be up to 10 times larger than what
      would be produced without the effects of wing-wing interaction. As the horizontal
      components of the forces generated during the end of the upstroke and beginning
      of the downstroke cancel as a result of the motion of the two wings, these forces
      cannot be used to generate thrust. As a result, clap and fling appears to be
      rather inefficient for the smallest flying insects. We also add flexibility to
      the wings and find that the maximum drag force generated during the fling can be
      reduced by about 50%. In some instances, the net lift forces generated are also
      improved relative to the rigid wing case.

PMID- 19749101
TI  - The influence of ambient temperature and thermal acclimation on hearing in a
      eurythermal and a stenothermal otophysan fish.
AB  - Being ectothermic, fish body temperature generally depends on ambient water
      temperature. Thus, ambient temperature might affect various sensory systems,
      including hearing, as a result of metabolic and physiological processes. However,
      the maintenance of sensory functions in a changing environment may be crucial for
      an animal's survival. Many fish species rely on hearing for acoustic orientation
      and communication. In order to investigate the influence of temperature on the
      auditory system, channel catfish Ictalurus punctatus was chosen as a model for a
      eurytherm species and the tropical catfish Pimelodus pictus as a model for a
      stenotherm fish. Hearing sensitivity was measured with animals acclimated or
      unacclimated to different water temperatures. Ambient water temperature
      significantly influenced hearing thresholds and the shape of auditory evoked
      potentials, especially at higher frequencies in I. punctatus. Hearing sensitivity
      of I. punctatus was lowest at 10 degrees C and increased by up to 36 dB between
      10 degrees C and 26 degrees C. Significant differences were also revealed between
      acclimated and unacclimated animals after an increase in water temperature but
      not a decrease. By contrast, differences in hearing thresholds were smaller in P.
      pictus, even if a similar temperature difference (8 degrees C) was considered.
      However, P. pictus showed a similar trend as I. punctatus in exhibiting higher
      hearing sensitivity at the highest tested temperature, especially at the highest
      frequency tested. The results therefore suggest that the functional temperature
      dependence of sensory systems may differ depending upon whether a species is
      physiologically adapted to tolerate a wide or narrow temperature range.

PMID- 19749102
TI  - Acoustic behaviour of echolocating porpoises during prey capture.
AB  - Porpoise echolocation has been studied previously, mainly in target detection
      experiments using stationed animals and steel sphere targets, but little is known
      about the acoustic behaviour of free-swimming porpoises echolocating for prey.
      Here, we used small onboard sound and orientation recording tags to study the
      echolocation behaviour of free-swimming trained porpoises as they caught dead,
      freely drifting fish. We analysed porpoise echolocation behaviour leading up to
      and following prey capture events, including variability in echolocation in
      response to vision restriction, prey species, and individual porpoise tested. The
      porpoises produced echolocation clicks as they searched for the fish, followed by
      fast-repetition-rate clicks (echolocation buzzes) when acquiring prey. During
      buzzes, which usually began when porpoises were about 1-2 body lengths from prey,
      tag-recorded click levels decreased by about 10 dB, click rates increased to over
      300 clicks per second, and variability in body orientation (roll) increased.
      Buzzes generally continued beyond the first contact with the fish, and often
      extended until or after the end of prey handling. This unexplained continuation
      of buzzes after prey capture raises questions about the function of buzzes,
      suggesting that in addition to providing detailed information on target location
      during the capture, they may serve additional purposes such as the relocation of
      potentially escaping prey. We conclude that porpoises display the same overall
      acoustic prey capture behaviour seen in larger toothed whales in the wild, albeit
      at a faster pace, clicking slowly during search and approach phases and buzzing
      during prey capture.

PMID- 19749103
TI  - Endocrine mechanisms mediating temperature-induced reproductive behavior in red
      sided garter snakes (Thamnophis sirtalis parietalis).
AB  - We investigated the mechanisms by which temperature induces seasonal reproductive
      behavior in red-sided garter snakes (Thamnophis sirtalis parietalis).
      Specifically, we addressed whether elevated temperatures during winter dormancy
      influence (1) diel melatonin and corticosterone rhythms; (2) sex steroid hormone
      and corticosterone profiles; and (3) the expression of reproductive behavior
      following emergence. Elevated hibernation temperatures (i.e. 10 degrees C versus
      5 degrees C) significantly increased overall melatonin and decreased
      corticosterone concentrations of snakes. The temperature-induced differences in
      melatonin rhythms between the 5 degrees C and 10 degrees C treatment groups
      persisted even after both groups were again acclimated to 10 degrees C,
      indicating that cold temperature exposure has a lasting influence on melatonin
      rhythms. Elevated hibernation temperatures also significantly altered androgen
      and corticosterone profiles of snakes, providing a potential mechanism to explain
      reported annual variation in steroid hormones. Although previous studies indicate
      that male red-sided garter snakes exhibit a dissociated reproductive strategy, we
      demonstrate the presence of intersexual variation in sex steroid hormone
      profiles, as estradiol concentrations of female snakes increased significantly
      prior to spring mating activity. Importantly, the percentage change in body mass
      did not differ significantly between snakes in the hibernation treatments,
      indicating that the observed changes in hormone profiles are indeed temperature
      induced and not simply an indirect result of significant changes in the energy
      balance of snakes. Finally, in males maintained at 10 degrees C during winter
      dormancy the onset of courtship behavior following emergence was delayed. Our
      results suggest that environmental temperatures induce reproductive behavior, in
      part, via changes in diel melatonin and/or corticosterone rhythms in this
      seasonally breeding reptile.

PMID- 19749104
TI  - Navigational abilities of adult and experienced homing pigeons deprived of
      olfactory or trigeminally mediated magnetic information.
AB  - Anatomical evidence and conditioning experiments have suggested that
      magnetoreceptors innervated by the ophthalmic branch of the trigeminal nerve are
      located in the upper beak of homing pigeons. Following these findings it has been
      proposed that the trigeminally-mediated magnetorececeptors are able to detect
      magnetic field intensity, which might be useful for a position finding mechanism
      for pigeons homing from unfamiliar locations. Recent data have shown that, in
      inexperienced pigeons, section of the ophthalmic branch of the trigeminal nerve
      does not impair navigational abilities. Similarly, no impairment was observed if
      the trigeminal section was performed on young pigeons, before they have had the
      opportunity to learn a navigational map. By contrast, section of the olfactory
      nerve either in adult inexperienced pigeons or in young birds before map
      learning, disrupted their homing performance. Nevertheless, because a magnetic
      map mechanism requires training flights for learning the magnetic gradient of the
      territory around the loft, the question remains as to whether the navigational
      performance of adult experienced pigeons can be affected by lack of magnetic
      information. To answer this question we extensively group-trained adult pigeons
      and then surgically deprived them of either olfactory or trigeminally mediated
      magnetic information, prior to testing their navigational abilities. The birds
      deprived of trigeminally mediated magnetic information displayed similar
      navigational abilities as intact control pigeons, whereas the olfactory-deprived
      pigeons were dramatically impaired in homing. Our data show that even in trained
      adult pigeons, olfactory cues are needed for homing from unfamiliar locations and
      that the lack of magnetic information does not affect navigational abilities of
      experienced adult homing pigeons.

PMID- 19749105
TI  - The effects of testosterone on immune function in quail selected for divergent
      plasma corticosterone response.
AB  - The immunocompetence handicap hypothesis (ICHH) suggests that the male sex
      hormone testosterone has a dual effect; it controls the development and
      expression of male sexually selected signals, and it suppresses the immune
      system. Therefore only high quality males are able to fully express secondary
      sexual traits because only they can tolerate the immunosuppressive qualities of
      testosterone. A modified version of the ICHH suggests that testosterone causes
      immunosuppression indirectly by increasing the stress hormone corticosterone
      (CORT). Lines of Japanese quail (Coturnix japonica) selected for divergent
      responses in levels of plasma CORT were used to test these hypotheses. Within
      each CORT response line (as well as in a control stock) we manipulated levels of
      testosterone in castrated quail by treatment with zero (sham), low or high
      testosterone implants, before testing the birds' humoral immunity and
      phytohaemagglutinin (PHA)-induced immune response, as well as body condition. The
      PHA-induced response was not significantly affected by CORT selected line,
      testosterone treatment or their interaction. There was, however, a significant
      effect of CORT line on humoral immunity in that the control birds exhibited the
      greatest antibody production, but there was no significant effect of testosterone
      manipulation on humoral immunity. The males in the sham implant treatment group
      had significantly greater mass than the males in the high testosterone group,
      suggesting a negative effect of high testosterone on general body condition. We
      discuss these results in the context of current hypotheses in the field of sexual
      selection.

PMID- 19749106
TI  - Metabolic function in Drosophila melanogaster in response to hypoxia and pure
      oxygen.
AB  - This study examined the metabolic response of Drosophila melanogaster exposed to
      O(2) concentrations ranging from 0 to 21% and at 100%. The metabolic rate of
      flies exposed to graded hypoxia remained nearly constant as O(2) tensions were
      reduced from normoxia to approximately 3 kPa. There was a rapid, approximately
      linear reduction in fly metabolic rate at P(O(2))s between 3 and 0.5 kPa. The
      reduction in metabolic rate was especially pronounced at P(O(2)) levels <0.5 kPa,
      and at a P(O(2)) of 0.1 kPa fly metabolic rate was reduced approximately 10-fold
      relative to normoxic levels. The metabolic rate of flies exposed to anoxia and
      then returned to normoxia recovered to pre-anoxic levels within 30 min with no
      apparent payment of a hypoxia-induced oxygen debt. Flies tolerated exposure to
      hypoxia and/or anoxia for 40 min with nearly 100% survival. Fly mortality
      increased rapidly after 2 h of anoxia and >16 h exposure was uniformly lethal.
      Flies exposed to pure O(2) for 24 h showed no apparent alteration of metabolic
      rate, even though such O(2) tensions should damage respiratory enzymes critical
      to mitochondria function. Within a few hours the metabolic rate of flies
      recovering from exposure to repeated short bouts of anoxia was the same as flies
      exposed to a single anoxia exposure.

PMID- 19749107
TI  - Functional differences between two CRF-related diuretic hormone receptors in
      Drosophila.
AB  - In Drosophila, two related G-protein-coupled receptors are members of the
      corticotropin releasing factor (CRF) receptor subfamily. We have previously
      reported that one of these receptors, encoded by CG8422 is a functional receptor
      for a diuretic hormone, DH(44). Here, we report that the other CRF receptor
      subfamily member, encoded by CG12370, is also a receptor for the DH(44)
      neuropeptide. The lines of evidence to support this identification include
      increases in cAMP levels due to CG12370 receptor activation and the recruitment
      of beta-arrestin-GFP to the plasma membrane in response to DH(44) application. We
      compared these features of the receptors DH44-R2 (encoded by CG12370) and DH44-R1
      (encoded by CG8422) and found fundamental differences in signaling, association
      with the arrestins, and peptide sensitivity. We found that the sensitivity of
      DH44-R2 to the DH(44) peptide is lower than that of DH44-R1, specifically an
      estimated EC(50) of 7.98E-07 moll(-1) for DH(44) by DH44-R2 to an EC(50) of 5.12E
      09 moll(-1) by DH44-R1 and found that previous reports on the sensitivity of the
      tubule to DH(44) is in agreement with our measurements of DH44-R2 sensitivity. We
      employed a specific RNAi construct to selectively knock-down DH44-R2 expression
      and this led to heightened sensitivity to osmotic challenges. The functional
      characterization of this diuretic hormone receptor in Drosophila demonstrates a
      high degree of conservation of CRF-like signaling.

PMID- 19749108
TI  - Wetting properties on nanostructured surfaces of cicada wings.
AB  - This study has investigated the wettability of forewings of 15 species of
      cicadas, with distinctly different wetting properties related to their
      nanostructures. The wing surfaces exhibited hydrophilic or weak to strong
      hydrophobic properties with contact angles ranging from 76.8 deg. to 146.0 deg.
      The nanostructures (protrusions), observed using environmental scanning electron
      microscopy (ESEM), were classified into four types according to the patterning,
      diameter (82-148 nm), spacing (44-117 nm) and height (159-446 nm). Surface
      analysis by X-ray photoelectron spectroscopy (XPS) showed significant differences
      in wing membrane chemistry. Thus, wetting properties at the macroscopic scale
      were dependent on slight differences in nanoscale architecture and composition of
      the wax layer. This investigation offers insights into the diversity of
      nanostructuring and how subtle small-scale changes may facilitate large changes
      in wettability.

PMID- 19749109
TI  - Oxygen tension correlates with regional blood flow in obstructed rat kidney.
AB  - As renal tissue oxygen tension (P(O(2))) is determined by the balance between
      oxygen supply and consumption, direct tissue P(O(2)) measurements are essential
      when evaluating the presence of hypoxia. The present study aimed at evaluating
      invasively and continuously the renal medullary and cortical tissue P(O(2)) by
      novel fibre-optic probes in rats subjected to acute unilateral ureteral
      obstruction (AUUO). In parallel, regional blood flow measurements were obtained
      by MRI to investigate the relationship between regional blood flow and tissue
      oxygen tension. The abundance of transport proteins was determined by
      immunoblotting. In the obstructed kidney, AUUO caused a prompt decrease in
      medullary tissue P(O(2)) to 60% of baseline level whereas cortical tissue P(O(2))
      was unchanged. By contrast, tissue P(O(2)) slightly increased in the non
      obstructed kidney. These changes developed during the first 30 min after AUUO and
      persisted for the 3 h observation period. Medullary blood flow declined 1.5-2 h
      after induction of AUUO to 61% of baseline level in the obstructed kidney. By
      contrast, cortical blood flow increased to 108% of baseline level in the non
      obstructed kidney. Finally, the abundance of phosphorylated aquaporin 2 decreased
      significantly in the obstructed kidney medulla, but increased in the obstructed
      kidney cortex. The Na(+)/K(+)-ATPase abundance increased in the obstructed kidney
      medulla whereas the Na(+)/K(+)/2Cl(-) co-transporter abundance remained unchanged
      in the obstructed kidney. In conclusion, measurements of regional blood flow
      reflect tissue P(O(2)) changes during AUUO suggesting that reduced regional blood
      flow is a predictor of local hypoxia. Furthermore, the abundance of major
      transport protein is independent of tissue P(O(2)).

PMID- 19749110
TI  - Evidence for age-dependent mating strategies in the simultaneous hermaphrodite
      snail, Lymnaea stagnalis (L.).
AB  - In many mating systems female reproductive capacity is a limiting resource over
      which males will compete. As a consequence, males and females have usually
      different fitness optimization strategies which may give rise to sexual conflict.
      Since simultaneous hermaphrodites have, in theory, the option to mate as male or
      as female at any time, conflict will occur if partners insist in taking the same
      role. Several lines of evidence exists that body size influences gender choice.
      However, growth in many invertebrates is indeterminate and therefore age is
      generally a covariant of size. We therefore investigated the effect of age on
      mating choices in the simultaneous hermaphrodite Lymnaea stagnalis. Using fully
      sexually mature animals sampled from three different age groups we show that
      copulation frequency declines with age. Specifically, in age-matched couples the
      frequency of primary and reciprocal copulations declines with age. Furthermore,
      the younger partner tends to mate as male with greater probability in couples of
      unequal age. Size was never a factor in the sex role preference of Lymnaea. Thus,
      young Lymnaea always attempt to copulate as male independent of the age of their
      partner, whereas senior snails act primarily as female. The sex role choices of
      middle-aged snails appear to depend on their partner's age. In addition, we
      demonstrate that the likelihood that an animal will copulate as male is not
      correlated with prostate gland size but correlates with the level of afferent
      electrical activity recorded in the nerve originating in the prostate gland.
      Together, our results indicate the existence of an age- and not size-dependent
      mating system in Lymnaea.

PMID- 19749111
TI  - Effects of physical interference on life history shifts in Daphnia pulex.
AB  - Daphnia pulex were reared in 50 ml flasks, each containing 1, 20 or 40
      individuals, which were serially connected with a 20-mum mesh screens between, in
      order to examine the effect of physical interference due to crowding on shifts of
      life history traits throughout two consecutive generations. A flow-through
      system, designed to maintain a sufficient food supply and minimize the
      accumulation of metabolites, was used. To eliminate the effect of infochemicals
      from crowded animals, a single-individual treatment flask was connected to two
      crowded flasks. In the first generation, D. pulex reared under crowded conditions
      grew more slowly after day 4 when oogenesis normally starts, and produced less
      offspring after day 9, compared with an animal reared alone, even when supplied
      with sufficient food. Although second generation daphniids of each treatment
      matured faster than in the first generation, crowded females grew more slowly
      even after day 2 and produced less offspring than single females. Age to maturity
      was no different between treatments in both generations. Crowded females,
      therefore, matured to smaller sizes but produced larger neonates compared with
      single females. Weight-specific reproduction rates of the first clutch were not
      significantly different between the treatments. These results suggest that
      physical interference between neighboring individuals due to crowding negatively
      affects growth and reproduction in daphniids. Crowded daphniids may allocate more
      energy to reproduction in order to produce larger and more starvation-tolerant
      offspring in preparation for severe food shortages. Crowding also triggered
      ephippial egg production and reduced survival compared with the single-individual
      treatment.

PMID- 19749112
TI  - Hierarchical organisation of the trap in the protocarnivorous plant Roridula
      gorgonias (Roridulaceae).
AB  - The flypaper trap of the protocarnivorous plant Roridula gorgonias is known to
      capture various insects, even those having a considerable body size, by using an
      adhesive, visco-elastic resinous secretion released by glandular trichomes of
      different dimensions. However, recent experimental studies have shown that the
      adhesion of long tentacle-shaped trichome secretion is not as strong as
      previously assumed. One may then ask why this flypaper trap is so highly
      effective. In the present study, we compared geometry, flexibility and the
      adhesive properties of secretion in different sized trichomes. We have analysed
      the gross morphology of the plant and its surfaces using light and cryo-scanning
      electron microscopy. Trichomes' stiffness and the adhesive properties of their
      secretion on different surfaces were measured. A combination of structural and
      experimental results, presented in this study, let us suggest that R. gorgonias
      represents a three-dimensional trap consisting of three functional hierarchical
      levels (plant, leaves and trichomes). According to their size, we classified
      three types of trichomes having a particular arrangement on the leaf. The longest
      trichomes are more flexible and less adhesive compared with the shortest ones.
      The latter are 48 times stiffer and their secretion has a 9 times higher adhesive
      strength. Our data support the hypothesis that the shortest trichomes are adapted
      to strong, long-term adherence to prey insects, and that the longest trichomes
      are responsible for initial trapping and entanglement function.

PMID- 19749114
TI  - Magnesium: an emerging drug in anaesthesia.

PMID- 19749115
TI  - Transversus abdominis plane block: what is its role in postoperative analgesia?

PMID- 19749116
TI  - Do approved blood substitutes reduce myocardial infarction size: is this the
      critical question?

PMID- 19749117
TI  - Economic aspects of regional anaesthesia.

PMID- 19749118
TI  - Four cases of anaphylaxis to chlorhexidine impregnated central venous catheters:
      a case cluster or the tip of the iceberg?

PMID- 19749119
TI  - Ehlers-Danlos syndrome type IV in a child admitted in emergency with peritonitis.

PMID- 19749120
TI  - Bispectral index may not reflect the depth of anaesthesia in a patient with
      glycogen storage disease type I.

PMID- 19749121
TI  - Non-acidotic propofol infusion syndrome.

PMID- 19749122
TI  - Re: Addition of clonidine or dexmedetomidine to bupivacaine prolongs caudal
      analgesia in children.

PMID- 19749125
TI  - Physicians, the industry and population health.

PMID- 19749126
TI  - Influenza A (H1N1) pandemic: true or false alarm.

PMID- 19749127
TI  - Proposal of new ICD code for suicide by charcoal burning.

PMID- 19749128
TI  - Influenza A (H1N1) pandemic: true or false alarm.

PMID- 19749129
TI  - Proposed obesity body mass index correction for self-reported data may not be
      appropriate.

PMID- 19749130
TI  - The European (ECCO) Consensus on infection in IBD: what does it change for the
      clinician?

PMID- 19749131
TI  - Difficulty in swallowing.

PMID- 19749132
TI  - Differences in post-inflammatory hypersensitivity between splanchnic and pelvic
      afferents: mechanisms and implications for human disease.

PMID- 19749133
TI  - Plasma microRNAs: a potential biomarker for colorectal cancer?

PMID- 19749134
TI  - Albumin and stellate cell activation: wonders will never cease!

PMID- 19749135
TI  - Screening for familial pancreatic cancer: is doing something better than doing
      nothing?

PMID- 19749136
TI  - Epigastric pain in a man with previous subtotal gastrectomy.

PMID- 19749137
TI  - A "stitch in time".

PMID- 19749138
TI  - History reveals the cause of rectal bleeding.

PMID- 19749139
TI  - Dysphagia in a 27-year-old man.

PMID- 19749140
TI  - "A flare" in a patient with known inflammatory bowel disease.

PMID- 19749141
TI  - Inflammatory bowel disease and lymphoproliferative disorders: the dust is
      starting to settle.
AB  - The risk of lymphoproliferative disorders (LDs) has become a major concern for
      clinicians managing patients with inflammatory bowel disease (IBD). Yet it is
      difficult to distinguish the possible responsibility of immunosuppressive therapy
      from the background risk due to the inflammatory disorder itself. LDs are clonal
      B or T cell proliferation showing considerable heterogeneity and the incidence
      has increased since the 1970s. The strongest and best-established risk factors
      for LDs are primary and acquired immunodeficiency (HIV, immunosuppressant),
      notably via defective immune surveillance of Epstein-Barr virus. In many auto
      immune diseases (eg, Sjogren's syndrome), inflammatory diseases (eg, rheumatoid
      arthritis) or chronic suppuration (chronic pyothorax), the risk of LD is
      increased. In IBD patients, in general, the risk of LD seems to be similar to or
      very slightly higher than in the general population. The role of
      immunosuppressants in lymphomagenesis is difficult to individualise because other
      factors potentially involved are inter-linked. Concordant data suggest that
      thiopurine therapy is associated with a moderately increased risk of LD. Data
      regarding methotrexate are scarce and come from diseases other than IBD but the
      risk seems low. Data regarding risk of LD in IBD patients receiving anti-tumour
      necrosis factor alpha (TNFalpha) agents are insufficient at this time, mainly
      because most of the patients are co-treated with thiopurines. The recently
      individualised risks of hepatosplenic T cell lymphoma and fatal post
      mononucleosis LD, in young male patients with IBD who are co-treated with anti
      TNFalpha and thiopurines, and EBV-seronegative IBD males, respectively, are
      probably low but remain to be better quantified.

PMID- 19749142
TI  - Endovascular treatment of immature, dysfunctional and thrombosed forearm
      autogenous ulnar-basilic and radial-basilic fistulas for haemodialysis.
AB  - BACKGROUND: Forearm basilic fistulas are rarely used as vascular accesses for
      haemodialysis but they represent a valuable option when autogenous radial
      cephalic fistulas cannot be performed. There is no information in the literature
      to date about the outcome of direct ulnar-basilic or transposed radial-basilic
      forearm autogenous fistulas after endovascular treatment of stenosis or
      thrombosis. METHODS: This retrospective study included 78 consecutive patients
      from eight dialysis units who were referred to a single interventional radiology
      centre for endovascular treatment of delayed maturation (n = 30), dysfunction (n
      = 35) or thrombosis (n = 13) of their autogenous forearm ulnar-basilic (n = 62)
      or radial-basilic fistulas (n = 16). The male/female ratio was 54/24, mean age
      was 64.7 years, 26% had diabetes, 83% were treated for hypertension and the mean
      body mass index was 24 kg/m(2). Immature and dysfunctional fistulas were treated
      by dilation and thrombosed fistulas by aspiration thrombectomy. Clinical success
      was defined as the perception of a continuous palpable thrill and the ability to
      perform dialysis. Fistula patency rates were calculated with the Kaplan-Meier
      method. RESULTS: Overall primary patency rates were 51% and 44% at 1 and 2 years,
      respectively. These rates were lower for immature and thrombosed fistulas
      compared to dysfunctional mature fistulas. Secondary patency rates were 96% and
      91% at 1 and 4 years, respectively. Immediate overall clinical success was 97%.
      The two failures occurred with an immature and a thrombosed fistula. Immediate
      complications included two transient dilation-induced ruptures treated by
      prolonged balloon inflation. One case of subsequent hand ischaemia was
      successfully treated by distal artery ligation. CONCLUSIONS: Endovascular
      treatment plays a major role in the maturation process, maintenance and salvage
      of radial and ulnar-basilic fistulas. The preservation of upper arm veins for the
      future, with low risk of hand ischaemia or hyperflow, might encourage
      nephrologists and surgeons to consider forearm basilic fistulas systematically in
      their strategy of vascular access creation.

PMID- 19749143
TI  - Association of low serum 25-hydroxyvitamin D levels and high arterial blood
      pressure in the elderly.
AB  - BACKGROUND: Vitamin D and calcium metabolism are involved in vascular smooth
      muscle cell proliferation, endothelial function and blood pressure (BP)
      regulation. Their physiopathology has been a matter of intensive clinical
      investigation with variable and sometimes contradictory results. Vitamin D
      insufficiency is highly prevalent in the general population, particularly among
      the elderly. We evaluated the association between serum 25(OH)-D levels and
      arterial BP in this population. METHODS: An epidemiological cross-sectional study
      was designed to analyse the prevalence of hypovitaminosis D ('D'AVIS' study) in
      our reference area. The study was performed on a representative random sample of
      the population over 64 years of age obtained from five primary health care areas.
      A medical record, arterial BP and biological analysis: serum 25(OH)-D, iPTH,
      creatinine, urea, calcium, albumin were obtained. RESULTS: A total of 237
      subjects (53% women), aged between 64 and 93 (mean 71.7 +/- 5.3), were evaluated.
      The mean serum 25(OH)-D levels were 17.21 +/- 7.57 ng/ml (interval 5-54; 86% had
      <25 ng/ml). The mean BP was 138.8 +/- 14/80 +/- 7.4 mmHg, and 46% were on
      antihypertensive treatment. A significant negative association was observed
      between serum 25(OH)-D levels and systolic (r = -0.153, P = 0.018) and diastolic
      BP (r = -0.152, P = 0.019). This association persisted after controlling for
      possible confounders in the multivariate analyses. CONCLUSIONS: Low serum 25(OH)
      D levels were inversely and independently associated with BP. Supplemental
      measures to prevent hypovitaminosis D in this population would be important, not
      only to protect the skeletal system but also for the possible beneficial effects
      on the cardiovascular system and the BP regulation.

PMID- 19749144
TI  - What is the relevance of systematic aorto-femoral Doppler ultrasound in the
      preoperative assessment of patients awaiting first kidney transplantation: a
      monocentric prospective study.
AB  - BACKGROUND: The purpose of our study was to study the relevance of a systematic
      aorto-femoral colour Doppler ultrasound (DUS) in the evaluation of first renal
      transplant receivers. METHODS: We prospectively studied 100 consecutive first
      renal transplant (RT) receivers. All patients had a preoperative physical
      examination with a careful vascular system evaluation including assessment of
      risk factors and colour DUS of aortic, iliac and femoral arteries. Renal
      transplantation was planned in the right iliac fossa with end-to-lateral vascular
      anastomoses. Clinical parameters, DUS results, operative and post-operative
      parameters at 3 months were compared according to the vascular assessment.
      RESULTS: Among the 84 patients presenting with a normal preoperative physical
      arterial examination, 12 patients (14.3%) had an abnormal DUS, revealing
      atherosclerotic arteries, but no case of arterial stenosis. Among the 16 patients
      with abnormal physical arterial examination, 10 patients (62.5%) had abnormal
      DUS, including 4 cases of iliac stenosis. In 3 of the 16 patients (18.8%), DUS
      revealed right iliac artery stenosis requiring a modification in the surgical
      procedure. No additional vascular procedure was reported in the case of normal
      preoperative vascular examination. No technical problems during arterial
      anastomosis and no post-transplantation arterial complications were reported. In
      multivariate analysis, abnormal physical examination was the most significant
      risk factor of atherosclerotic infiltration in DUS. CONCLUSION: The abnormality
      of arterial physical examination is the best clinical predictor of abnormal DUS
      in preoperative assessment of renal transplant receivers. However, the low
      sensitivity and positive predictive value of the physical examination do not
      support the conclusion that DUS can be avoided in patients with normal arterial
      physical examination. Nevertheless, in the case of arterial physical abnormality,
      'for case' DUS is critical and helps in the surgical strategy in approximately
      20% of cases.

PMID- 19749145
TI  - Age and cystatin C in healthy adults: a collaborative study.
AB  - BACKGROUND: Kidney function declines with age, but a substantial portion of this
      decline has been attributed to the higher prevalence of risk factors for kidney
      disease at older ages. The effect of age on kidney function has not been well
      described in a healthy population across a wide age spectrum. METHODS: The
      authors pooled individual-level cross-sectional data from 18 253 persons aged 28
      100 years in four studies: the Cardiovascular Health Study; the Health, Aging and
      Body Composition Study; the Multi-Ethnic Study of Atherosclerosis and the
      Prevention of Renal and Vascular End-Stage Disease cohort. Kidney function was
      measured by cystatin C. Clinical risk factors for kidney disease included
      diabetes, hypertension, obesity, smoking, coronary heart disease, cerebrovascular
      disease, peripheral arterial disease and heart failure. RESULTS: Across the age
      range, there was a strong, non-linear association of age with cystatin C
      concentration. This association was substantial, even among participants free of
      clinical risk factors for kidney disease; mean cystatin C levels were 46% higher
      in participants 80 and older compared with those <40 years (1.06 versus 0.72
      mg/L, P < 0.001). Participants with one or more risk factors had higher cystatin
      C concentrations for a given age, and the age association was slightly stronger
      (P < 0.001 for age and risk factor interaction). CONCLUSIONS: There is a strong,
      non-linear association of age with kidney function, even in healthy individuals.
      An important area for research will be to investigate the mechanisms that lead to
      deterioration of kidney function in apparently healthy persons.

PMID- 19749146
TI  - Tempol or candesartan prevents high-fat diet-induced hypertension and renal
      damage in spontaneously hypertensive rats.
AB  - BACKGROUND: Obesity has been strongly associated with the development and
      aggravation of hypertension and chronic kidney disease. To date, the systemic
      renin-angiotensin system (RAS) has been known to involve in obesity-induced
      tissue damage and hypertension. However, the intrarenal mechanism whereby obesity
      induces and aggravates hypertension and renal disease remains poorly understood.
      Therefore, we investigated the role of intrarenal RAS and oxidative stress in
      diet-induced hypertension and renal inflammation in spontaneously hypertensive
      rats (SHR) fed a high-fat diet. METHODS: Male SHR and Wistar-Kyoto rats (WKY)
      were divided into eight groups: normal-fat diet-fed WKY (WKY-NF), high-fat diet
      fed WKY (WKY-HF), high-fat diet-fed tempol-treated WKY (WKY-HF/T), high-fat diet
      fed candesartan-treated WKY (WKY-HF/C), normal-fat diet-fed SHR (SHR-NF), high
      fat diet-fed SHR (SHR-HF), high-fat diet-fed tempol-treated SHR (SHR-HF/T) and
      high-fat diet-fed candesartan-treated SHR (SHR-HF/C). After 12 weeks of
      treatment, haemodynamic measurements and histological assessment of the kidney
      were performed. RESULTS: At the end of week 12, the high-fat fed SHR gained more
      body weight, their systolic blood pressure was further elevated and glucose
      intolerance induced. There was no significant difference in the insulin
      resistance index, serum lipid profile, plasma renin activity and serum
      aldosterone levels according to diet. However, the high-fat diet resulted in
      increases in immunohistochemical stains of renin and angiotensin II in the
      kidney. The real-time PCR also demonstrated significant increases in mRNA levels
      of renin, angiotensinogen and angiotensin-converting enzyme in the kidney,
      reflecting enhanced activation of the intrarenal RAS, which findings were also
      shown by Western blot analysis for renin and angiotensin II type 1 receptor. The
      expression of ED-1, osteopontin and TGF-beta1 in the renal cortex were
      prominently enhanced in the SHR-HF group with the increased intrarenal lipid
      concentrations and oxidative stress. Administration of tempol or candesartan in
      the high-fat diet-induced SHR inhibited the elevation of the systolic blood
      pressure, intrarenal lipid concentrations, oxidative stress and the degree of
      renal inflammation to the levels of, or more than, the SHR-NF with no differences
      in the body weight and periepididymal fat weight, compared to those in the SHR-HF
      group without such treatment. CONCLUSIONS: Our study suggests that a high-fat
      diet induces fatty kidneys, aggravation of blood pressure and renal inflammation
      in the SHR. Blockade of oxidative stress by tempol or of RAS by candesartan
      ameliorates the increase in blood pressure and renal inflammation and improves
      intrarenal lipid accumulation. Therefore, antioxidants or angiotensin receptor
      blockers can prevent diet-induced hypertension and renal inflammation in
      hypertensive rats.

PMID- 19749147
TI  - Survival of transplanted and dialysed patients in a French region with focus on
      outcomes in the elderly.
AB  - BACKGROUND: Impact of kidney transplantation on survival of French end-stage
      renal disease (ESRD) patients is unknown. METHODS: A total of 1495 adults living
      in the Lorraine region and starting renal replacement therapy from 1997 to 2003
      were included. A propensity score (PS) of registration on the renal transplant
      waiting list was estimated. Patient survival was studied using a time-dependent
      Cox multivariate regression and a Cox model stratified by PS tertiles. Survival
      of older patients (> or =60 years) was detailed. RESULTS: Survival was associated
      with age, medical factors and transplantation. The hazard ratio (HR) of death for
      patients on dialysis compared to transplant recipients was 4.6 (95% CI: 2.9-7.2).
      The survival analysis stratified by PS was similar to the multivariate Cox model.
      The survival benefit of transplantation over dialysis persisted among elderly
      patients [HR: 4.6 (95% CI: 2.2-9.7)]. CONCLUSIONS: In a French community-based
      network, after taking into account comorbidities, transplantation was associated
      with longer survival even among elderly patients. Age per se should not therefore
      be considered as a contraindication to renal transplantation. However, elderly
      patients should be evaluated carefully before registration on the list. Medical
      guidelines should put forward a standard set of criteria for access to renal
      transplantation.

PMID- 19749148
TI  - Non-diphtheria corynebacteria and CAPD infections.

PMID- 19749149
TI  - Detecting potential respiratory pathogens in the mouths of older people in
      hospital.

PMID- 19749151
TI  - Evolution of AGL6-like MADS box genes in grasses (Poaceae): ovule expression is
      ancient and palea expression is new.
AB  - AGAMOUS-like6 (AGL6) genes encode MIKC-type MADS box transcription factors and
      are closely related to SEPALLATA and AP1/FUL-like genes. Here, we focus on the
      molecular evolution and expression of the AGL6-like genes in grasses. We have
      found that AGL6-like genes are expressed in ovules, lodicules (second whorl
      floral organs), paleas (putative first whorl floral organs), and floral
      meristems. Each of these expression domains was acquired at a different time in
      evolution, indicating that each represents a distinct function of the gene
      product and that the AGL6-like genes are pleiotropic. Expression in the inner
      integument of the ovule appears to be an ancient expression pattern corresponding
      to the expression of the gene in the megasporangium and integument in
      gymnosperms. Expression in floral meristems appears to have been acquired in the
      angiosperms and expression in second whorl organs in monocots. Early in grass
      evolution, AGL6-like orthologs acquired a new expression domain in the palea.
      Stamen expression is variable. Most grasses have a single AGL6-like gene
      (orthologous to the rice [Oryza sativa] gene MADS6). However, rice and other
      species of Oryza have a second copy (orthologous to rice MADS17) that appears to
      be the result of an ancient duplication.

PMID- 19749152
TI  - bearded-ear encodes a MADS box transcription factor critical for maize floral
      development.
AB  - Although many genes that regulate floral development have been identified in
      Arabidopsis thaliana, relatively few are known in the grasses. In normal maize
      (Zea mays), each spikelet produces an upper and lower floral meristem, which
      initiate floral organs in a defined phyllotaxy before being consumed in the
      production of an ovule. The bearded-ear (bde) mutation affects floral development
      differently in the upper and lower meristem. The upper floral meristem initiates
      extra floral organs that are often mosaic or fused, while the lower floral
      meristem initiates additional floral meristems. We cloned bde by positional
      cloning and found that it encodes zea agamous3 (zag3), a MADS box transcription
      factor in the conserved AGAMOUS-LIKE6 clade. Mutants in the maize homolog of
      AGAMOUS, zag1, have a subset of bde floral defects. bde zag1 double mutants have
      a severe ear phenotype, not observed in either single mutant, in which floral
      meristems are converted to branch-like meristems, indicating that bde and zag1
      redundantly promote floral meristem identity. In addition, BDE and ZAG1
      physically interact. We propose a model in which BDE functions in at least three
      distinct complexes to regulate floral development in the maize ear.

PMID- 19749153
TI  - Specific targeting of the Arabidopsis resistance protein RPW8.2 to the
      interfacial membrane encasing the fungal Haustorium renders broad-spectrum
      resistance to powdery mildew.
AB  - Powdery mildew fungal pathogens penetrate the plant cell wall and develop a
      feeding structure called the haustorium to steal photosynthetate from the host
      cell. Here, we report that the broad-spectrum mildew resistance protein RPW8.2
      from Arabidopsis thaliana is induced and specifically targeted to the
      extrahaustorial membrane (EHM), an enigmatic interfacial membrane believed to be
      derived from the host cell plasma membrane. There, RPW8.2 activates a salicylic
      acid (SA) signaling-dependent defense strategy that concomitantly enhances the
      encasement of the haustorial complex and onsite accumulation of H(2)O(2),
      presumably for constraining the haustorium while reducing oxidative damage to the
      host cell. Targeting of RPW8.2 to the EHM, however, is SA independent and
      requires function of the actin cytoskeleton. Natural mutations that impair either
      defense activation or EHM targeting of RPW8.2 compromise the efficacy of RPW8.2
      mediated resistance. Thus, the interception of haustoria is key for RPW8-mediated
      broad-spectrum mildew resistance.

PMID- 19749154
TI  - A small GTPase of the Rab family is required for root hair formation and
      preinfection stages of the common bean-Rhizobium symbiotic association.
AB  - Legume plants are able to establish a symbiotic relationship with soil bacteria
      from the genus Rhizobium, leading to the formation of nitrogen-fixing root
      nodules. Successful nodulation requires both the formation of infection threads
      (ITs) in the root epidermis and the activation of cell division in the cortex to
      form the nodule primordium. This study describes the characterization of RabA2, a
      common bean (Phaseolus vulgaris) cDNA previously isolated as differentially
      expressed in root hairs infected with Rhizobium etli, which encodes a protein
      highly similar to small GTPases of the RabA2 subfamily. This gene is expressed in
      roots, particularly in root hairs, where the protein was found to be associated
      with vesicles that move along the cell. The role of this gene during nodulation
      has been studied in common bean transgenic roots using a reverse genetic
      approach. Examination of root morphology in RabA2 RNA interference (RNAi) plants
      revealed that the number and length of the root hairs were severely reduced in
      these plants. Upon inoculation with R. etli, nodulation was completely impaired
      and no induction of early nodulation genes (ENODs), such as ERN1, ENOD40, and
      Hap5, was detected in silenced hairy roots. Moreover, RabA2 RNAi plants failed to
      induce root hair deformation and to initiate ITs, indicating that morphological
      changes that precede bacterial infection are compromised in these plants. We
      propose that RabA2 acts in polar growth of root hairs and is required for
      reorientation of the root hair growth axis during bacterial infection.

PMID- 19749155
TI  - Decreased PPAR gamma expression compromises perigonadal-specific fat deposition
      and insulin sensitivity.
AB  - Mutations and polymorphisms in PPARG have been linked to adiposity and partial
      lipodystrophy in humans. However, how disturbances in PPARG lead to depot
      specific effects on adipose tissue, as shown by the characteristic aberrant fat
      distribution in patients, remains unclear. By manipulating the 3'-untranslated
      region of the Pparg gene, we have generated mice with peroxisome proliferator
      activated receptor gamma (PPAR gamma) gene expression ranging from 25% to 100%
      normal. Basal levels of PPAR gamma transcripts between 50% and approximately 100%
      had no significant effect on body weight, fat mass, and insulin sensitivity. In
      contrast, mice with 25% normal PPAR gamma expression exhibited reduced body
      weight and total fat mass, insulin resistance, and dyslipidemia. Interestingly,
      fat mass was selectively reduced in perigonadal depot without significant changes
      in inguinal and other depots. Expression of adipogenic factor CCAAT enhancer
      binding protein-alpha and some other metabolic genes containing peroxisome
      proliferator response element were reduced in a perigonadal depot-specific
      fashion. This was further associated with depot-specific reduction in the
      expression of adipokines, increased expression of TNFalpha, and increased ectopic
      lipid deposition in muscles. Together, these results underscore the differential
      sensitivity of the individual fat depots on PPAR gamma availability as an
      underlying mechanism of partial lipodystrophy.

PMID- 19749156
TI  - G protein-coupled receptor 30 expression is up-regulated by EGF and TGF alpha in
      estrogen receptor alpha-positive cancer cells.
AB  - In the present study, we evaluated the regulation of G protein-coupled receptor
      (GPR)30 expression in estrogen receptor (ER)-positive endometrial, ovarian, and
      estrogen-sensitive, as well as tamoxifen-resistant breast cancer cells. We
      demonstrate that epidermal growth factor (EGF) and TGF alpha transactivate the
      GPR30 promoter and accordingly up-regulate GPR30 mRNA and protein levels only in
      endometrial and tamoxifen-resistant breast cancer cells. These effects exerted by
      EGF and TGF alpha were dependent on EGF receptor (EGFR) expression and activation
      and involved phosphorylation of the Tyr(1045) and Tyr(1173) EGFR sites. Using
      gene-silencing experiments and specific pharmacological inhibitors, we have
      ascertained that EGF and TGF alpha induce GPR30 expression through the EGFR/ERK
      transduction pathway, and the recruitment of c-fos to the activator protein-1
      site located within GPR30 promoter sequence. Interestingly, we show that
      functional cross talk of GPR30 with both activated EGFR and ER alpha relies on a
      physical interaction among these receptors, further extending the potential of
      estrogen to trigger a complex stimulatory signaling network in hormone-sensitive
      tumors. Given that EGFR/HER2 overexpression is associated with tamoxifen
      resistance, our data may suggest that ligand-activated EGFR could contribute to
      the failure of tamoxifen therapy also by up-regulating GPR30, which in turn could
      facilitates the action of estrogen. In addition, important for resistance is the
      ability of tamoxifen to bind to and activate GPR30, the expression of which is up
      regulated by EGFR activation. Our results emphasize the need for new endocrine
      agents able to block widespread actions of estrogen without exerting any
      stimulatory activity on transduction pathways shared by the steroid and growth
      factor-signaling networks.

PMID- 19749157
TI  - Resveratrol attenuates mitochondrial oxidative stress in coronary arterial
      endothelial cells.
AB  - The production of hyperglycemia-induced mitochondrial reactive oxygen species
      (mtROS) is a key event in the development of diabetic complications. Because
      resveratrol, a naturally occurring polyphenol, has been reported to confer
      vasoprotection, improving endothelial function and preventing complications of
      diabetes, we investigated the effect of resveratrol on mtROS production in
      cultured human coronary arterial endothelial cells (CAECs). The measurement of
      MitoSox fluorescence showed that resveratrol attenuates both steady-state and
      high glucose (30 mM)-induced mtROS production in CAECs, an effect that was
      prevented by the knockdown of the protein deacetylase silent information
      regulator 2/sirtuin 1 (SIRT1), an intracellular target of resveratrol. An
      overexpression of SIRT1 mimicked the effects of resveratrol, attenuating mtROS
      production. Similar results were obtained in CAECs transfected with mitochondria
      targeted H(2)O(2)-sensitive HyPer-Mito fluorescent sensor. Amplex red assay
      showed that resveratrol and SIRT1 overexpression significantly reduced cellular
      H(2)O(2) levels as well. Resveratrol upregulated MnSOD expression and increased
      cellular GSH content in a concentration-dependent manner (measured by HPLC
      coulometric analysis). These effects were attenuated by SIRT1 knockdown and
      mimicked by SIRT1 overexpression. We propose that resveratrol, via a pathway that
      involves the activation of SIRT1 and the upregulation of antioxidant defense
      mechanisms, attenuates mtROS production, suggesting the potential for new
      treatment approaches targeting endothelial mitochondria in metabolic diseases.

PMID- 19749158
TI  - Angiotensin II enhances GABA(B) receptor-mediated responses and expression in
      nucleus tractus solitarii of rats.
AB  - Angiotensin II (ANG II) increases GABA(B) receptor expression in neuronal
      cultures from the nucleus tractus solitarii (NTS). In the present study, the
      chronic effects of ANG II on GABA(B) receptor expression and activity were
      examined in the NTS of Sprague-Dawley rats. Intracerebroventricular infusion of
      ANG II caused a significant elevation in blood pressure (BP) and an increase in
      GABA(B) receptor expression in the NTS. Conversely, chronic N(G)-nitro-l-arginine
      methyl ester (l-NAME) treatment also increased BP, but had no effect on GABA(B)
      receptor expression in the NTS. Next, we examined the BP response to the GABA(B)
      receptor agonist baclofen microinjected into the NTS of ANG II- or artificial
      cerebrospinal fluid (aCSF)-infused rats. NTS microinjection of baclofen increased
      BP in both groups of rats. However, the pressor response to baclofen was enhanced
      in ANG II-infused rats compared with aCSF-infused rats. In addition, bilateral
      microinjection of the GABA(B) receptor antagonist CGP-35348 into the NTS evoked a
      decrease in BP in both group of rats, and the depressor responses to CGP-35348
      were enhanced in the ANG II-infused rats. In contrast, the pressor responses to
      the GABA(A) receptor agonist muscimol and the depressor responses to the GABA(A)
      receptor antagonist bicuculline were comparable between aCSF- and ANG II-infused
      rats. These results indicate that chronic ANG II infusion stimulates GABA(B)
      receptor expression and augments GABA(B) receptor-mediated responses in the NTS.
      This effect could contribute to the central nervous system actions of ANG II that
      result in dampening of baroreflexes and elevation in arterial BP.

PMID- 19749159
TI  - A random cycle length approach for assessment of myocardial contraction in
      isolated rabbit myocardium.
AB  - It is well known that the strength of cardiac contraction is dependent on the
      cycle length, evidenced by the force-frequency relationship (FFR) and the
      existence of postrest potentiation (PRP). Because the contractile strength of the
      steady-state FFR and force-interval relationship involve instant intrinsic
      responses to cycle length as well as slower acting components such as
      posttranslational modification-based mechanisms, it remains unclear how cycle
      length intrinsically affects cardiac contraction and relaxation. To dissect the
      impact of cycle length changes from slower acting signaling components associated
      with persisting changes in cycle length, we developed a novel technique/protocol
      to study cycle length-dependent effects on cardiac function; twitch contractions
      of right ventricular rabbit trabeculae at different cycle lengths were randomized
      around a steady-state frequency. Patterns of cycle lengths that resulted in
      changes in force and/or relaxation times can now be identified and analyzed.
      Using this novel protocol, taking under 10 min to complete, we found that the
      duration of the cycle length before a twitch contraction ("primary" cycle length)
      positively correlated with force. In sharp contrast, the cycle length one
      ("secondary") or two ("tertiary") beats before the analyzed twitch correlated
      negatively with force. Using this protocol, we can quantify the intrinsic effect
      of cycle length on contractile strength while avoiding rundown and lengthiness
      that are often complications of FFR and PRP assessments. The data show that the
      history of up to three cycle lengths before a contraction influences myocardial
      contractility and that primary cycle length affects cardiac twitch dynamics in
      the opposite direction from secondary/tertiary cycle lengths.

PMID- 19749160
TI  - Lack of cardiac fibrosis in a new model of high prorenin hyperaldosteronism.
AB  - The aim of the present study was to test the hypothesis that elevation of
      prorenin in plasma is sufficient to induce cardiac fibrosis. Normotensive
      cyp1a1ren-2 transgenic rats with normal plasma prorenin and aldosterone levels
      were given 0.125% indole-3-carbinol (I3C) orally for a period of 12 wk. Plasma
      prorenin and aldosterone levels were determined in 4-wk intervals, and cardiac
      marker enzymes for hypertrophy, fibrosis, and oxidative stress as well as cardiac
      pathology were investigated. In I3C-treated cyp1a1 ren-2 transgenic rats, plasma
      prorenin concentrations were >100-fold elevated (> or = 7.1 + or - 2.6 microg ANG
      I.ml(-1).h(-1) vs. < or = 0.07 + or - 0.1; P < 0.001), whereas active renin
      levels were suppressed (0.09 + or - 0.02 vs. 0.2 + or - 0.1; P < 0.05).
      Aldosterone concentrations were elevated three- to fourfold for a period of >4 wk
      (574 + or - 51 vs. 160 + or - 68 pg/ml; P < 0.01). After 12 wk of I3C, rats
      exhibited moderate cardiac hypertrophy (heart weight/body weight 2.5 + or - 0.04
      vs. 3.1 + or - 0.1 mg/g; P < 0.01). There was a slight increase in mRNA contents
      of endothelin 1 (1.21 + or - 0.08 vs. 0.75 + or - 0.007; P < 0.001), NADP oxidase
      2 (1.03 + or - 0.006 vs. 0.76 + or - 0.04; P < 0.001), transforming growth factor
      beta (0.99 + or - 0.06 vs. 0.84 + or - 0.04; P < 0.05), collagen type I (1.32 +
      or - 0.32 vs. 0.94 + or - 0.18; P < 0.05), and intercellular adhesion molecule-1
      (1.12 + or - 0.12 vs. 0.84 + or - 0.08; P < 0.05). These genes are known to be
      stimulated by the renin-angiotensin system. There were no histological signs of
      fibrosis in the heart. We found that prorenin and aldosterone alone are not
      sufficient to induce considerable cardiac fibrosis in the absence of sodium load.

PMID- 19749161
TI  - BK channels in cardiovascular disease: a complex story of channel dysregulation.

PMID- 19749162
TI  - Calcineurin and cardiac function: is more or less better for the heart?

PMID- 19749163
TI  - Maturation and the role of PKC-mediated contractility in ovine cerebral arteries.
AB  - Ca2+-independent pathways such as protein kinase C (PKC), extracellular-regulated
      kinases 1 and 2 (ERK1/2), and Rho kinase 1 and 2 (ROCK1/2) play important roles
      in modulating cerebral vascular tone. Because the roles of these kinases vary
      with maturational age, we tested the hypothesis that PKC differentially regulates
      the Ca2+-independent pathways and their effects on cerebral arterial
      contractility with development. We simultaneously examined the responses of
      arterial tension and intracellular Ca2+ concentration and used Western immunoblot
      analysis to measure ERK1/2, RhoA, 20 kDa regulatory myosin light chain (MLC20),
      PKC-potentiated inhibitory protein of 17 kDa (CPI-17), and caldesmon. Phorbol
      12,13-dibutyrate (PDBu)-mediated PKC activation produced a robust contractile
      response, which was increased a further 20 to 30% by U-0126 (MEK inhibitor) in
      cerebral arteries of both age groups. Of interest, in the fetal cerebral
      arteries, PDBu leads to an increased phosphorylation of ERK2 compared with ERK1,
      whereas in adult arteries, we observed an increased phosphorylation of ERK1
      compared with ERK2. Also, in the present study, RhoA/ROCK played a significant
      role in the PDBu-mediated contractility of fetal cerebral arteries, whereas in
      adult cerebral arteries, CPI-17 and caldesmon had a significantly greater role
      compared with the fetus. PDBu also led to an increased MLC20 phosphorylation, a
      response blunted by the inhibition of myosin light chain kinase only in the
      fetus. Overall, the present study demonstrates an important maturational shift
      from RhoA/ROCK-mediated to CPI-17/caldesmon-mediated PKC-induced contractile
      response in ovine cerebral arteries.

PMID- 19749164
TI  - Impaired function of coronary BK(Ca) channels in metabolic syndrome.
AB  - The role of large-conductance Ca(2+)-activated K(+) (BK(Ca)) channels in
      regulation of coronary microvascular function is widely appreciated, but
      molecular and functional changes underlying the deleterious influence of
      metabolic syndrome (MetS) have not been determined. Male Ossabaw miniature swine
      consumed for 3-6 mo a normal diet (11% kcal from fat) or an excess-calorie
      atherogenic diet that induces MetS (45% kcal from fat, 2% cholesterol, 20% kcal
      from fructose). MetS significantly impaired coronary vasodilation to the BK(Ca)
      opener NS-1619 in vivo (30-100 microg) and reduced the contribution of these
      channels to adenosine-induced microvascular vasodilation in vitro (1-100 microM).
      MetS reduced whole cell penitrem A (1 microM)-sensitive K(+) current and NS-1619
      activated (10 microM) current in isolated coronary vascular smooth muscle cells.
      MetS increased the concentration of free intracellular Ca(2+) and augmented
      coronary vasoconstriction to the L-type Ca(2+) channel agonist BAY K 8644 (10 pM
      10 nM). BK(Ca) channel alpha and beta(1) protein expression was increased in
      coronary arteries from MetS swine. Coronary vascular dysfunction in MetS is
      related to impaired BK(Ca) channel function and is accompanied by significant
      increases in L-type Ca(2+) channel-mediated coronary vasoconstriction.

PMID- 19749165
TI  - Replicative senescence of vascular smooth muscle cells enhances the calcification
      through initiating the osteoblastic transition.
AB  - Medial artery calcification, which does not accompany lipid or cholesterol
      deposit, preferentially occurs in elderly population, but its underlying
      mechanisms remain unclear. In the present study, we investigated the potential
      role of senescent vascular smooth muscle cells (VSMCs) in the formation of
      senescence-associated medial calcification. Replicative senescence was induced by
      the extended passages (until passages 11-13) in human primary VSMCs, and cells in
      early passage (passage 6) were used as control young cells. VSMC calcification
      was markedly enhanced in the senescent cells compared with that in the control
      young cells. We identified that genes highly expressed in osteoblasts, such as
      alkaline phosphatase (ALP) and type I collagen, were significantly upregulated in
      the senescent VSMCs, suggesting their osteoblastic transition during the
      senescence. Knockdown of either ALP or type I collagen significantly reduced the
      calcification in the senescent VSMCs. Of note, runt-related transcription factor
      2 (RUNX-2), a core transcriptional factor that initiates the osteoblastic
      differentiation, was also upregulated in the senescent VSMCs. Knockdown of RUNX-2
      significantly reduced the ALP expression and calcification in the senescent
      VSMCs, suggesting that RUNX-2 is involved in the senescence-mediated osteoblastic
      transition. Furthermore, immunohistochemistry of aorta from the klotho(-/-) aging
      mouse model demonstrated in vivo emergence of osteoblast-like cells expressing
      RUNX-2 exclusively in the calcified media. We also found that statin and Rho
      kinase inhibitor effectively reduced the VSMC calcification by inhibiting P(i)
      induced apoptosis and potentially enhancing matrix Gla protein expression in the
      senescent VSMCs. These findings strongly suggest an important role of senescent
      VSMCs in the pathophysiology of senescence-associated medial calcification, and
      the inhibition of osteoblastic transition could be a new therapeutic approach for
      the prevention of senescence-associated medial calcification.

PMID- 19749166
TI  - Vasopressin is a major vasoconstrictor involved in hindlimb vascular responses to
      stimulation of adenosine A(1) receptors in the nucleus of the solitary tract.
AB  - Our previous study showed that stimulation of adenosine A(1) receptors located in
      the nucleus of the solitary tract (NTS) exerts counteracting effects on the iliac
      vascular bed: activation of the adrenal medulla and beta-adrenergic vasodilation
      versus vasoconstriction mediated by neural and unknown humoral factors. In the
      present study we investigated the relative contribution of three major potential
      humoral vasoconstrictors: vasopressin, angiotensin II, and norepinephrine in this
      response. In urethane-chloralose anesthetized rats we compared the integral
      changes in iliac vascular conductance evoked by microinjections into the NTS of
      the selective A(1) receptor agonist N(6)-cyclopentyladenosine (CPA; 330 pmol in
      50 nl) in intact (Int) animals and following: V(1) vasopressin receptor blockade
      (VX), angiotensin II AT(1) receptor blockade (ATX), bilateral adrenalectomy +
      ganglionic blockade (ADX + GX; which eliminated the potential increases in
      circulating norepinephrine and epinephrine), ADX + GX + VX and ADX + GX + VX +
      ATX. In Int animals, stimulation of NTS A(1) adenosine receptors evoked typical
      variable responses with prevailing pressor and vasoconstrictor effects. VX
      reversed the responses to depressor ones. ATX did not significantly alter the
      responses. ADX + GX accentuated pressor and vasoconstrictor responses, whereas
      ADX + GX + VX and ADX + GX + VX + ATX virtually abolished the responses.
      Stimulation of NTS A(1) adenosine receptors increased circulating vasopressin
      over fourfold (26.4 + or - 10.4 vs. 117.0 + or - 19 pg/ml). These data strongly
      suggest that vasopressin is a major vasoconstrictor factor opposing beta
      adrenergic vasodilation in iliac vascular responses triggered by stimulation of
      NTS A(1) adenosine receptors, whereas angiotensin II and norepinephrine do not
      contribute significantly to the vasoconstrictor responses.

PMID- 19749167
TI  - Absence of adenosine-mediated aortic relaxation in A(2A) adenosine receptor
      knockout mice.
AB  - Adenosine mediates vascular responses through four receptor subtypes: A(1),
      A(2A), A(2B), and A(3). The role of A(2A) receptors in aortic vascular tone was
      investigated using A(2A) adenosine receptor (AR) knockout (A(2A)KO) and
      corresponding wild-type (A(2A)WT) mice. Isolated aortic rings from A(2A)WT and
      A(2A)KO mice were precontracted with phenylephrine (10(-7) M), and concentration
      responses for adenosine analogs and selective agonists/antagonists were obtained.
      Nonselective adenosine analog (NECA; EC(50) = 6.78 microM) and CGS-21680 (A(2A)AR
      selective agonist; EC(50) = 0.013 microM) produced concentration-dependent
      relaxation (maximum of 25% and 28% relaxation at 10(-5) M NECA and CGS-21680,
      respectively) in A(2A)WT aorta. In A(2A)KO aorta, NECA (EC(50) = 0.075 microM)
      induced concentration-dependent contraction (maximum contraction of 47% at 10(-6)
      M; P < 0.05 compared with A(2A)WT), whereas CGS-21680 produced no response. SCH
      58261 (10(-6) M; A(2A)AR selective antagonist) abolished both NECA- and CGS-21680
      mediated vasorelaxation in A(2A)WT (P < 0.05), whereas no change was observed in
      A(2A)KO. When DPCPX (10(-5) M; A(1) selective antagonist) was used in NECA
      concentration response, greater vasorelaxation was observed in A(2A)WT (50% vs.
      25% in controls at 10(-5) M; P < 0.05), whereas lower contraction was seen in
      A(2A)KO tissues (5% vs. 47% in controls at 10(-6) M; P < 0.05). Aortic
      endothelial function, determined by response to acetylcholine, was significantly
      higher in WT compared with KO (66% vs. 51%; P < 0.05). BAY 60-6583 (A(2B)
      selective agonist) produced similar relaxation in both KO and WT tissues. In
      conclusion, A(2A)AR KO mice had significantly lower aortic relaxation and
      endothelial function, suggesting that the A(2A)AR plays an important role in
      vasorelaxation, probably through an endothelium-dependent mechanism.

PMID- 19749168
TI  - Pharmacological modifications of the stretch-induced effects on ventricular
      fibrillation in perfused rabbit hearts.
AB  - Stretch induces modifications in myocardial electrical and mechanical activity.
      Besides the effects of substances that block the stretch-activated channels,
      other substances could modulate the effects of stretch through different
      mechanisms that affect Ca(2+) handling by myocytes. Thirty-six Langendorff
      perfused rabbit hearts were used to analyze the effects of the Na(+)/Ca(2+)
      exchanger blocker KB-R7943, propranolol, and the adenosine A(2) receptor
      antagonist SCH-58261 on the acceleration of ventricular fibrillation (VF)
      produced by acute myocardial stretching. VF recordings were obtained with two
      epicardial multiple electrodes before, during, and after local stretching in four
      experimental series: control (n = 9), KB-R7943 (1 microM, n = 9), propranolol (1
      microM, n = 9), and SCH-58261 (1 microM, n = 9). Both the Na(+)/Ca(2+) exchanger
      blocker KB-R7943 and propranolol induced a significant reduction (P < 0.001 and P
      < 0.05, respectively) in the dominant frequency increments produced by stretching
      with respect to the control and SCH-58261 series (control = 49.9%, SCH-58261 =
      52.1%, KB-R7943 = 9.5%, and propranolol = 12.5%). The median of the activation
      intervals, the functional refractory period, and the wavelength of the activation
      process during VF decreased significantly under stretch in the control and SCH
      58261 series, whereas no significant variations were observed in the propranolol
      and KB-R7943 series, with the exception of a slight but significant decrease in
      the median of the fibrillation intervals in the KB-R7943 series. KB-R7943 and
      propranolol induced a significant reduction in the activation maps complexity
      increment produced by stretch with respect to the control and SCH-58261 series.
      In conclusion, the electrophysiological effects responsible for stretch-induced
      VF acceleration in the rabbit heart are reduced by the Na(+)/Ca(2+) exchanger
      blocker KB-R7943 and by propranolol but not by the adenosine A(2) receptor
      antagonist SCH-58261.

PMID- 19749169
TI  - Extraction of morphometry and branching angles of porcine coronary arterial tree
      from CT images.
AB  - The morphometry (diameters, length, and angles) of coronary arteries is related
      to their function. A simple, easy, and accurate image-based method to seamlessly
      extract the morphometry for coronary arteries is of significant value for
      understanding the structure-function relation. Here, the morphometry of large (>
      or = 1 mm in diameter) coronary arteries was extracted from computed tomography
      (CT) images using a recently validated segmentation algorithm. The coronary
      arteries of seven pigs were filled with Microfil, and the cast hearts were imaged
      with CT. The centerlines of the extracted vessels, the vessel radii, and the
      vessel lengths were identified for over 700 vessel segments. The extraction
      algorithm was based on a topological analysis of a vector field generated by
      normal vectors of the extracted vessel wall. The diameters, lengths, and angles
      of the right coronary artery, left anterior descending coronary artery, and left
      circumflex artery of all vessels > or = 1 mm in diameter were tabulated for the
      respective orders. It was found that bifurcations at orders 9-11 are planar (
      approximately 90%). The relations between volume and length and area and length
      were also examined and found to scale as power laws. Furthermore, the bifurcation
      angles follow the minimum energy hypothesis but with significant scatter. Some of
      the applications of the semiautomated extraction of morphometric data in
      applications to coronary physiology and pathophysiology are highlighted.

PMID- 19749170
TI  - Myocardial ischemia and reperfusion injury is dependent on both IgM and mannose
      binding lectin.
AB  - Complement activation has been shown to play an important role in the
      inflammation and tissue injury following myocardial ischemia and reperfusion
      (MI/R). Several recent studies from our laboratory demonstrated the importance of
      mannose-binding lectin (MBL) as the initiation pathway for complement activation
      and the resulting pathological effects following MI/R. However, other studies
      from the past suggest an important role of the classical pathway and perhaps
      natural antibodies. In the present study, we used newly generated genetically
      modified mice that lack secreted IgM (sIgM), MBL-A, and MBL-C (sIgM/MBL null) in
      a plasma reconstitution mouse model of MI/R. Following 30 min of ischemia and 4 h
      of reperfusion, left ventricular ejection fractions were significantly higher in
      sIgM/MBL null mice reconstituted with MBL null or sIgM/MBL null plasma compared
      with reconstitution with wild-type (WT) plasma or WT mice reconstituted with WT
      plasma following MI/R. Serum troponin I concentration, myocardial
      polymorphonuclear leukocyte infiltration, and C3 deposition were dependent on the
      combined presence of sIgM and MBL. These results demonstrate that MI/R-induced
      complement activation, inflammation, and subsequent tissue injury require both
      IgM and MBL. Thus MBL-dependent activation of the lectin pathway may not be
      completely antibody independent in I/R models.

PMID- 19749172
TI  - Pathomechanisms of type 2 diabetes genes.
AB  - Type 2 diabetes mellitus is a complex metabolic disease that is caused by insulin
      resistance and beta-cell dysfunction. Furthermore, type 2 diabetes has an evident
      genetic component and represents a polygenic disease. During the last decade,
      considerable progress was made in the identification of type 2 diabetes risk
      genes. This was crucially influenced by the development of affordable high
      density single nucleotide polymorphism (SNP) arrays that prompted several
      successful genome-wide association scans in large case-control cohorts.
      Subsequent to the identification of type 2 diabetes risk SNPs, cohorts thoroughly
      phenotyped for prediabetic traits with elaborate in vivo methods allowed an
      initial characterization of the pathomechanisms of these SNPs. Although the
      underlying molecular mechanisms are still incompletely understood, a surprising
      result of these pathomechanistic investigations was that most of the risk SNPs
      affect beta-cell function. This favors a beta-cell-centric view on the genetics
      of type 2 diabetes. The aim of this review is to summarize the current knowledge
      about the type 2 diabetes risk genes and their variants' pathomechanisms.

PMID- 19749173
TI  - Conservation of the sterol regulatory element-binding protein pathway and its
      pathobiological importance in Cryptococcus neoformans.
AB  - The mammalian sterol regulatory element-binding protein (SREBP) homolog, Sre1, is
      important for adaptation and growth of Cryptococcus neoformans in the mouse
      brain, where oxygen concentration and nutritional conditions are suboptimal for
      fungal growth. The extent of conservation of the SREBP pathway in C. neoformans
      or in any other fungi, however, has not been investigated. We generated mutants
      susceptible to low oxygen and identified six genes that play a role in the SREBP
      pathway. Three of these genes (SFB2, KAP123, and GSK3) are not known to be
      involved in the SREBP pathway in other fungi. Furthermore, we show that C.
      neoformans contains an additional gene, DAM1, which functions in the SREBP
      pathway but is yet to be described. Mutants associated with the steps prior to
      formation of the nuclear Sre1 form dramatically reduced accumulation of the
      nuclear form under low-oxygen conditions. Concurrently, two mutant strains,
      scp1Delta and stp1Delta, and the previously isolated sre1Delta strain showed
      reduction in ergosterol levels, hypersensitivity to several chemical agents,
      including azole antifungals, CoCl(2), and compounds producing reactive oxygen or
      nitrogen species, and most importantly, reduced virulence in mice. Mutants
      affecting genes involved in later steps of the Sre1 pathway, such as those
      required for import and phosphorylation of proteins in the nucleus, showed less
      compelling phenotypes. These findings suggest that the SREBP pathway is highly
      conserved in C. neoformans and it serves as an important link between sterol
      biosynthesis, oxygen sensing, CoCl(2) sensitivity, and virulence in C.
      neoformans.

PMID- 19749171
TI  - The transient receptor potential vanilloid-1 channel in thermoregulation: a
      thermosensor it is not.
AB  - The development of antagonists of the transient receptor potential vanilloid-1
      (TRPV1) channel as pain therapeutics has revealed that these compounds cause
      hyperthermia in humans. This undesirable on-target side effect has triggered a
      surge of interest in the role of TRPV1 in thermoregulation and revived the
      hypothesis that TRPV1 channels serve as thermosensors. We review literature data
      on the distribution of TRPV1 channels in the body and on thermoregulatory
      responses to TRPV1 agonists and antagonists. We propose that two principal
      populations of TRPV1-expressing cells have connections with efferent
      thermoeffector pathways: 1) first-order sensory (polymodal), glutamatergic dorsal
      root (and possibly nodose) ganglia neurons that innervate the abdominal viscera
      and 2) higher-order sensory, glutamatergic neurons presumably located in the
      median preoptic hypothalamic nucleus. We further hypothesize that all
      thermoregulatory responses to TRPV1 agonists and antagonists and thermoregulatory
      manifestations of TRPV1 desensitization stem from primary actions on these two
      neuronal populations. Agonists act primarily centrally on population 2;
      antagonists act primarily peripherally on population 1. We analyze what roles
      TRPV1 might play in thermoregulation and conclude that this channel does not
      serve as a thermosensor, at least not under physiological conditions. In the
      hypothalamus, TRPV1 channels are inactive at common brain temperatures. In the
      abdomen, TRPV1 channels are tonically activated, but not by temperature. However,
      tonic activation of visceral TRPV1 by nonthermal factors suppresses autonomic
      cold-defense effectors and, consequently, body temperature. Blockade of this
      activation by TRPV1 antagonists disinhibits thermoeffectors and causes
      hyperthermia. Strategies for creating hyperthermia-free TRPV1 antagonists are
      outlined. The potential physiological and pathological significance of TRPV1
      mediated thermoregulatory effects is discussed.

PMID- 19749174
TI  - A contiguous compartment functions as endoplasmic reticulum and endosome/lysosome
      in Giardia lamblia.
AB  - The dynamic evolution of organelle compartmentalization in eukaryotes and how
      strictly compartmentalization is maintained are matters of ongoing debate. While
      the endoplasmic reticulum (ER) is classically envisioned as the site of protein
      cotranslational translocation, it has recently been proposed to have pluripotent
      functions. Using transfected reporter constructs, organelle-specific markers, and
      functional enzyme assays, we now show that in an early-diverging protozoan,
      Giardia lamblia, endocytosis and subsequent degradation of exogenous proteins
      occur in the ER or in an adjacent and communicating compartment. The Giardia
      endomembrane system is simple compared to those of typical eukaryotes. It lacks
      peroxisomes, a classical Golgi apparatus, and canonical lysosomes. Giardia
      orthologues of mammalian lysosomal proteases function within an ER-like
      tubulovesicular compartment, which itself can dynamically communicate with
      clathrin-containing vacuoles at the periphery of the cell to receive endocytosed
      proteins. These primitive characteristics support Giardia's proposed early
      branching and could serve as a model to study the compartmentalization of
      endocytic and lysosomal functions into organelles distinct from the ER. This
      system also may have functional similarity to the retrograde transport of toxins
      and major histocompatibility complex class I function in the ER of mammals.

PMID- 19749175
TI  - Horizontal chromosome transfer, a mechanism for the evolution and differentiation
      of a plant-pathogenic fungus.
AB  - The tomato pathotype of Alternaria alternata produces host-specific AAL toxin and
      causes Alternaria stem canker on tomato. A polyketide synthetase (PKS) gene,
      ALT1, which is involved in AAL toxin biosynthesis, resides on a 1.0-Mb
      conditionally dispensable chromosome (CDC) found only in the pathogenic and AAL
      toxin-producing strains. Genomic sequences of ALT1 and another PKS gene, both of
      which reside on the CDC in the tomato pathotype strains, were compared to those
      of tomato pathotype strains collected worldwide. This revealed that the sequences
      of both CDC genes were identical among five A. alternata tomato pathotype strains
      having different geographical origins. On the other hand, the sequences of other
      genes located on chromosomes other than the CDC are not identical in each strain,
      indicating that the origin of the CDC might be different from that of other
      chromosomes in the tomato pathotype. Telomere fingerprinting and restriction
      fragment length polymorphism analyses of the A. alternata strains also indicated
      that the CDCs in the tomato pathotype strains were identical, although the
      genetic backgrounds of the strains differed. A hybrid strain between two
      different pathotypes was shown to harbor the CDCs derived from both parental
      strains with an expanded range of pathogenicity, indicating that CDCs can be
      transmitted from one strain to another and stably maintained in the new genome.
      We propose a hypothesis whereby the ability to produce AAL toxin and to infect a
      plant could potentially be distributed among A. alternata strains by horizontal
      transfer of an entire pathogenicity chromosome. This could provide a possible
      mechanism by which new pathogens arise in nature.

PMID- 19749176
TI  - Distinct subsets of Sit4 holophosphatases are required for inhibition of
      Saccharomyces cerevisiae growth by rapamycin and zymocin.
AB  - Protein phosphatase Sit4 is required for growth inhibition of Saccharomyces
      cerevisiae by the antifungals rapamycin and zymocin. Here, we show that the
      rapamycin effector Tap42, which interacts with Sit4, is dispensable for zymocin
      action. Although Tap42 binding-deficient sit4 mutants are resistant to zymocin,
      these mutations also block interaction between Sit4 and the Sit4-associating
      proteins Sap185 and Sap190, previously shown to mediate zymocin toxicity. Among
      the four different SAP genes, we found that SAP190 deletions specifically induce
      rapamycin resistance but that this phenotype is reversed in the additional
      absence of SAP155. Similarly, the rapamycin resistance of an rrd1Delta mutant
      lacking the Sit4 interactor Rrd1 specifically requires the Sit4/Sap190 complex.
      Thus, Sit4/Sap190 and Sit4/Sap155 holophosphatases apparently play opposing roles
      following rapamycin treatment, although rapamycin inhibition is operational in
      the absence of all Sap family members or Sit4. We further identified a Sit4
      interacting region on Sap185 in sap190Delta cells that mediates Sit4/Sap185
      complex formation and is essential for dephosphorylation of Elp1, a subunit of
      the Elongator complex. This suggests that Sit4/Sap185 and Sit4/Sap190
      holophosphatases promote Elongator functions, a notion supported by data showing
      that their inactivation eliminates Elongator-dependent processes, including tRNA
      suppression by SUP4 and tRNA cleavage by zymocin.

PMID- 19749177
TI  - Reconstruction of signaling networks regulating fungal morphogenesis by
      transcriptomics.
AB  - Coordinated control of hyphal elongation and branching is essential for
      sustaining mycelial growth of filamentous fungi. In order to study the molecular
      machinery ensuring polarity control in the industrial fungus Aspergillus niger,
      we took advantage of the temperature-sensitive (ts) apical-branching ramosa-1
      mutant. We show here that this strain serves as an excellent model system to
      study critical steps of polar growth control during mycelial development and
      report for the first time a transcriptomic fingerprint of apical branching for a
      filamentous fungus. This fingerprint indicates that several signal transduction
      pathways, including TORC2, phospholipid, calcium, and cell wall integrity
      signaling, concertedly act to control apical branching. We furthermore identified
      the genetic locus affected in the ramosa-1 mutant by complementation of the ts
      phenotype. Sequence analyses demonstrated that a single amino acid exchange in
      the RmsA protein is responsible for induced apical branching of the ramosa-1
      mutant. Deletion experiments showed that the corresponding rmsA gene is essential
      for the growth of A. niger, and complementation analyses with Saccharomyces
      cerevisiae evidenced that RmsA serves as a functional equivalent of the TORC2
      component Avo1p. TORC2 signaling is required for actin polarization and cell wall
      integrity in S. cerevisiae. Congruently, our microscopic investigations showed
      that polarized actin organization and chitin deposition are disturbed in the
      ramosa-1 mutant. The integration of the transcriptomic, genetic, and phenotypic
      data obtained in this study allowed us to reconstruct a model for cellular events
      involved in apical branching.

PMID- 19749178
TI  - Overexpression of mitochondrial Leishmania major ascorbate peroxidase enhances
      tolerance to oxidative stress-induced programmed cell death and protein damage.
AB  - Ascorbate peroxidase from Leishmania major (LmAPX) is one of the key enzymes for
      scavenging of reactive oxygen species generated from the mitochondrial
      respiratory chain. We have investigated whether mitochondrial LmAPX has any role
      in oxidative stress-induced apoptosis. The measurement of reduced glutathione
      (GSH) and protein carbonyl contents in cellular homogenates indicates that
      overexpression of LmAPX protects Leishmania cells against depletion of GSH and
      oxidative damage of proteins by H(2)O(2) or camptothecin (CPT) treatment.
      Confocal microscopy and fluorescence spectroscopy data have revealed that the
      intracellular elevation of Ca(2+) attained by the LmAPX-overexpressing cells was
      always below that attained in control cells. Flow cytometry assay data and
      confocal microscopy observation strongly suggest that LmAPX overexpression
      protects cells from H(2)O(2)-induced mitochondrial membrane depolarization as
      well as ATP decrease. Western blot data suggest that overexpression of LmAPX
      shields against H(2)O(2)- or CPT-induced cytochrome c and endonuclease G release
      from mitochondria and subsequently their accumulation in the cytoplasm. Caspase
      activity assay by flow cytometry shows a lower level of caspase-like protease
      activity in LmAPX-overexpressing cells under apoptotic stimuli. The data on
      phosphatidylserine exposed on the cell surface and DNA fragmentation results show
      that overexpression of LmAPX renders the Leishmania cells more resistant to
      apoptosis provoked by H(2)O(2) or CPT treatment. Taken together, these results
      indicate that constitutive overexpression of LmAPX in the mitochondria of L.
      major prevents cells from the deleterious effects of oxidative stress, that is,
      mitochondrial dysfunction and cellular death.

PMID- 19749179
TI  - Differential effects of sphingosine 1-phosphate receptors on airway and vascular
      barrier function in the murine lung.
AB  - The therapeutic options for ameliorating the profound vascular permeability,
      alveolar flooding, and organ dysfunction that accompanies acute inflammatory lung
      injury (ALI) remain limited. Extending our previous finding that the intravenous
      administration of the sphingolipid angiogenic factor, sphingosine 1-phosphate
      (S1P), attenuates inflammatory lung injury and vascular permeability via ligation
      of S1PR(1), we determine that a direct intratracheal or intravenous
      administration of S1P, or a selective S1P receptor (S1PR(1)) agonist (SEW-2871),
      produces highly concentration-dependent barrier-regulatory responses in the
      murine lung. The intratracheal or intravenous administration of S1P or SEW-2871
      at < 0.3 mg/kg was protective against LPS-induced murine lung inflammation and
      permeability. However, intratracheal delivery of S1P at 0.5 mg/kg (for 2 h)
      resulted in significant alveolar-capillary barrier disruption (with a 42%
      increase in bronchoalveolar lavage protein), and produced rapid lethality when
      delivered at 2 mg/kg. Despite the greater selectivity for S1PR(1),
      intratracheally delivered SEW-2871 at 0.5 mg/kg also resulted in significant
      alveolar-capillary barrier disruption, but was not lethal at 2 mg/kg. Consistent
      with the S1PR(1) regulation of alveolar/vascular barrier function, wild-type mice
      pretreated with the S1PR(1) inverse agonist, SB-649146, or S1PR(1)(+/-) mice
      exhibited reduced S1P/SEW-2871-mediated barrier protection after challenge with
      LPS. In contrast, S1PR(2)(-/-) knockout mice as well as mice with reduced S1PR(3)
      expression (via silencing S1PR3-containing nanocarriers) were protected against
      LPS-induced barrier disruption compared with control mice. These studies
      underscore the potential therapeutic effects of highly selective S1PR(1) receptor
      agonists in reducing inflammatory lung injury, and highlight the critical role of
      the S1P delivery route, S1PR(1) agonist concentration, and S1PR(1) expression in
      target tissues.

PMID- 19749180
TI  - Dynamic and differential regulation of proteins that coat lipid droplets in fatty
      liver dystrophic mice.
AB  - Lipid droplet proteins (LDPs) coat the surface of triglyceride-rich lipid
      droplets and regulate their formation and lipolysis. We profiled hepatic LDP
      expression in fatty liver dystrophic (fld) mice, a unique model of neonatal
      hepatic steatosis that predictably resolves between postnatal day 14 (P14) and
      P17. Western blotting revealed that perilipin-2/ADRP and perilipin-5/OXPAT were
      markedly increased in steatotic fld liver but returned to normal by P17. However,
      the changes in perilipin-2 and perilipin-5 protein content in fld mice were
      exaggerated compared with relatively modest increases in corresponding mRNAs
      encoding these proteins, a phenomenon likely mediated by increased protein
      stability. Conversely, cell death-inducing DFFA-like effector (Cide) family genes
      were strongly induced at the level of mRNA expression in steatotic fld mouse
      liver. Surprisingly, levels of peroxisome proliferator-activated receptor gamma,
      which is known to regulate Cide expression, were unchanged in fld mice. However,
      sterol-regulatory element binding protein 1 (SREBP-1) was activated in fld liver
      and CideA was revealed as a new direct target gene of SREBP-1. In summary, LDP
      content is markedly increased in liver of fld mice. However, whereas perilipin-2
      and perilipin-5 levels are primarily regulated posttranslationally, Cide family
      mRNA expression is induced, suggesting that these families of LDP are controlled
      at different regulatory checkpoints.

PMID- 19749181
TI  - Neurodevelopmental and epilepsy outcomes in a North American cohort of patients
      with infantile spasms.
AB  - Studies have suggested disparate variables affecting long-term outcomes in
      patients with infantile spasms. Using a retrospective chart review, the authors
      identified 109 patients who had follow-up data for at least 1 year since the
      onset of spasms. Patient and treatment variables were recorded, in addition to
      neurodevelopmental and seizure outcomes. Etiology was strongly associated with
      motor and cognitive status but not with long-term seizure control. Lag time to
      initiation of treatment was not predictive of any outcome, nor for need to use a
      second agent to resolve spasms, even when controlling for etiology. However,
      patients who responded to the first medication achieved superior seizure and
      cognitive outcomes. The delayed impact of individual medications could not be
      analyzed because many patients received multiple agents. While etiology and
      response to first medication predict better outcomes, the majority of patients
      with infantile spasms continue to have epilepsy with long-term motor and
      cognitive disabilities.

PMID- 19749182
TI  - Multimodality neuroimaging in Tourette syndrome: alpha-[11C] methyl-L-tryptophan
      positron emission tomography and diffusion tensor imaging studies.
AB  - Previous studies in Tourette syndrome have reported lateralized abnormalities of
      neurotransmitters and microstructure of the cortico-striato-thalamo-cortical
      circuit. The authors analyzed the relationship between serotonin synthesis and
      microstructural changes in the subcortical structures (caudate nucleus, lentiform
      nucleus, and thalamus) related to this circuit, using alpha-[(11)C]methyl-L
      tryptophan positron emission tomography (PET) and diffusion tensor imaging,
      respectively, in 16 children with Tourette syndrome. Correlations between
      diffusion tensor imaging and alpha-[(11)C]methyl-L-tryptophan PET asymmetry
      values were found in the caudate nucleus. The findings suggested higher serotonin
      synthesis on the side of more abnormal diffusion, characterized by lower
      fractional anisotropy and parallel diffusivity but higher perpendicular
      diffusivity. Altogether, these imaging abnormalities suggest asymmetric immature
      microstructure in the caudate nucleus associated with abnormally increased
      serotonin synthesis in Tourette syndrome. The observed diffusion tensor imaging
      changes are likely related to abnormal connectivity in the cortico-striato
      thalamo-cortical circuit, which may result in cortical disinhibition and
      increased serotonin synthesis; this could provide a new therapeutic target.

PMID- 19749191
TI  - Strand displacement by DNA polymerase III occurs through a tau-psi-chi link to
      single-stranded DNA-binding protein coating the lagging strand template.
AB  - In addition to the well characterized processive replication reaction catalyzed
      by the DNA polymerase III holoenzyme on single-stranded DNA templates, the enzyme
      possesses an intrinsic strand displacement activity on flapped templates. The
      strand displacement activity is distinguished from the single-stranded DNA
      templated reaction by a high dependence upon single-stranded DNA binding protein
      and an inability of gamma-complex to support the reaction in the absence of tau.
      However, if gamma-complex is present to load beta(2), a truncated tau protein
      containing only domains III-V will suffice. This truncated protein is sufficient
      to bind both the alpha subunit of DNA polymerase (Pol) III and chipsi. This is
      reminiscent of the minimal requirements for Pol III to replicate short single
      stranded DNA-binding protein (SSB)-coated templates where tau is only required to
      serve as a scaffold to hold Pol III and chi in the same complex (Glover, B., and
      McHenry, C. (1998) J. Biol. Chem. 273, 23476-23484). We propose a model in which
      strand displacement by DNA polymerase III holoenzyme depends upon a Pol III-tau
      psi-chi-SSB binding network, where SSB is bound to the displaced strand,
      stabilizing the Pol III-template interaction. The same interaction network is
      probably important for stabilizing the leading strand polymerase interactions
      with authentic replication forks. The specificity constant (k(cat)/K(m)) for the
      strand displacement reaction is approximately 300-fold less favorable than
      reactions on single-stranded templates and proceeds with a slower rate (150
      nucleotides/s) and only moderate processivity (approximately 300 nucleotides).
      PriA, the initiator of replication restart on collapsed or misassembled
      replication forks, blocks the strand displacement reaction, even if added to an
      ongoing reaction.

PMID- 19749192
TI  - Advanced interpretation of the Neuropsychological Assessment Battery with older
      adults: base rate analyses, discrepancy scores, and interpreting change.
AB  - The purpose of this study is to provide sophisticated psychometric information
      for advanced interpretation of the Neuropsychological Assessment Battery (NAB)
      with older adults. This information includes the base rates of low scores,
      intellectual-cognitive discrepancy scores, and a method for determining change.
      The NAB contains 24 co-normed neurocognitive tests across five domains (i.e.,
      Attention, Language, Memory, Spatial, and Executive Functions); provides 36
      primary T-scores, five domain indexes, and a total index score; and was co-normed
      with a measure of intellectual abilities (Reynolds Intellectual Assessment
      Scales; Reynolds Intellectual Screening Test [RIST]). Participants for this study
      were 742 older adults from the NAB standardization sample (mean age = 68.1, SD =
      6.9). From the standardization sample, 42 older adults (mean age = 67.3 years, SD
      = 8.3) were administered the NAB two times (mean retest interval = 6.7 months, SD
      = 0.7). The base rates of low index scores and low primary scores are presented
      for the entire sample, as well as stratified by the level of intellectual
      abilities. RIST-NAB discrepancy scores are presented for the entire sample and
      for the different levels of intellectual abilities. Finally, information needed
      to interpret change in test performance on serial assessments is provided.

PMID- 19749193
TI  - The Groningen ART cohort study: ovarian hyperstimulation and the in vitro
      procedure do not affect neurological outcome in infancy.
AB  - BACKGROUND: Due to the growing number of children born following assisted
      reproduction technology, even subtle changes in the children's health and
      development are of importance to society at large. The aim of the present study
      was to evaluate the specific effects of ovarian hyperstimulation and the in vitro
      procedure on neurological outcome in 4-18-month-old children. METHODS: In this
      prospective assessor-blinded cohort study, we included singletons born following
      controlled ovarian hyperstimulation in vitro fertilization (IVF) or
      intracytoplasmic sperm injection (ICSI) (COH-IVF; n = 68) or modified natural
      cycle-IVF/ICSI (MNC-IVF; n = 57) or naturally conceived singletons of subfertile
      couples (NC; n = 90). Children were assessed with standardized, age-specific and
      sensitive neurological assessments (TINE and Hempel assessment) at 4, 10 and 18
      months. Neurological examination resulted in a neurological optimality score
      (NOS), a fluency score and a clinical neurological classification. Fluency of
      movements is easily affected by neurological dysfunction and is therefore a
      sensitive measure for minimal changes in neuromotor development. RESULTS: The NOS
      and the fluency score were similar in COH-IVF, MNC-IVF and NC children. None of
      the children showed major neurological dysfunction and rates of minor
      neurological dysfunction at the three ages were not different between the three
      conception groups. CONCLUSIONS: We found no effects of ovarian hyperstimulation
      or the in vitro procedure itself on neurological outcome in children aged 4-18
      months. The findings of our study are reassuring, nevertheless it should be kept
      in mind that subtle neurodevelopmental disorders may emerge when children grow
      older. Continuation of follow-up in older and larger groups of children is
      therefore still needed.

PMID- 19749194
TI  - Ultra-violet sterilization of liquid nitrogen prior to vitrification.

PMID- 19749195
TI  - A new method for testing a hypothesis on a cause of polycystic ovary syndrome.

PMID- 19749196
TI  - Tissue Doppler imaging and contrast-enhanced cardiac magnetic resonance in
      primary cardiac amyloidosis.
AB  - A 64-year-old female presented with biventricular heart failure. Echocardiography
      revealed features suggestive of amyloidosis, including segmental impairment of
      longitudinal strain (rate) in the septal and anterior segments, which matched
      delayed gadolinium-enhanced cardiac magnetic resonance. Guided endomyocardial
      biopsy confirmed the presence of perivascular amyloid deposits. Tissue Doppler
      and gadolinium-enhanced magnetic resonance may be helpful in delineating cardiac
      amyloidosis.

PMID- 19749197
TI  - Huge cardiac cyst hydatid causing cardiac symptoms and electrocardiographic
      changes.
AB  - Here we present a huge cardiac cyst hydatid case with wonderful echocardiographic
      and computed tomographic images, causing cardiac symptoms and
      electrocardiographic changes.

PMID- 19749198
TI  - Coronary artery-pulmonary artery fistula in a heart-transplanted patient.
AB  - A 64-year-old-man underwent routine elective right-left heart catheterization, 1
      year after cardiac transplantation for terminal ischaemic cardiomyopathy.
      Surprisingly, selective coronary angiography disclosed coronary-pulmonary artery
      fistula with three feeding vessels originating from the proximal right coronary
      artery, the proximal portion of the left anterior descending artery, the
      circumflexus artery, and the left main coronary artery, draining into the
      pulmonary trunk. For this particular patient, without any significant cardiac
      complaints or symptoms, with normal cardiac dimensions and haemodynamic findings,
      a conservative approach was decided on.

PMID- 19749200
TI  - A specimen preparation technique for plane-view studies of surfaces using
      transmission electron microscopy.
AB  - A method for preparing plane-view transmission electron microscope (TEM) samples
      is presented. With this inclined pseudo-plane-view technique, the undisturbed
      surface of the sample can be studied in plane view. Thus, nanostructures on the
      surface of a substrate can be studied with TEM in much the same way as with
      scanning electron microscopy (SEM), but in transmission at a much higher spatial
      resolution and with the opportunity of performing nanoscale diffraction. A glued
      sandwich with two surfaces facing each other was thinned at a low angle relative
      to the surfaces. The resultant construction contained thin wedges of the surfaces
      upon which it was possible to do TEM analysis. SEM analysis before and TEM
      analysis after such sample preparation was found to be consistent.

PMID- 19749199
TI  - Guidelines for the diagnosis and treatment of pulmonary hypertension.

PMID- 19749201
TI  - Impedance cardiography: a role in vasovagal syncope diagnosis?
AB  - BACKGROUND: vasovagal syncope is the most common cause of syncope in all age
      groups, with diagnosis usually based on history, examination and basic
      investigations to exclude alternative causes of syncope. Where doubt exists, the
      head-up tilt (HUT) test is used for diagnosis but is time consuming and lacks a
      gold standard to accurately assess sensitivity and specificity. Alternative
      methods of diagnosing vasovagal syncope would thus be useful. OBJECTIVE: to
      investigate the potential for impedance cardiography (ICG)-derived haemodynamic
      measures to predict HUT test outcome in unexplained syncope. DESIGN: prospective
      controlled study. SUBJECTS: eighty-six patients with unexplained syncope and 43
      non-syncopal controls. METHODS: all subjects underwent continuous heart rate,
      blood pressure and ICG measurements during 10 min supine rest and during HUT.
      Vasovagal syncope was diagnosed when patients experienced symptom reproduction
      with concomitant haemodynamic derangements. RESULTS: during rest prior to HUT,
      the syncopal group had higher mean heart rate (P = 0.0008) and lower baroreceptor
      effectiveness index (P < 0.0001) compared to non-syncopal controls. On comparing
      patients who presented with unexplained syncope who subsequently had a positive
      HUT (therefore a diagnosis of vasovagal syncope 55 [64%]; mean age 47 years,
      range 17-85) to those having a negative tilt test (n = 31; mean age 47 years,
      range 17-88), there were no significant differences found in cardiovascular or
      autonomic parameters prior to HUT. A predictive ROC curve model at a 85%
      threshold allowed using cardiac index (CI), end-diastolic index (EDI) and left
      ventricular work index (LVWI) would identify those who would have a positive HUT
      from baseline cardiovascular measurements (CI >3.5, EDI > 77, LVWI >4.7) with 93%
      sensitivity and 17% specificity. CONCLUSION: supine haemodynamic measures derived
      from transthoracic ICG can simply, non-invasively and sensitively differentiate
      HUT-positive patients from those with negative tilt tests. Further work is
      needed, particularly in older patients, before this technique can be used in
      clinical practice.

PMID- 19749202
TI  - Warfarin can be safe and effective in the extreme elderly.

PMID- 19749203
TI  - Mammalian cell ganglioside-binding specificities of E. coli enterotoxins LT-IIb
      and variant LT-IIb(T13I).
AB  - LT-IIb, a type II heat-labile enterotoxin of Escherichia coli, is a potent
      immunologic adjuvant with high affinity binding for ganglioside GD1a. Earlier
      study suggested that LT-IIb bound preferentially to the terminal sugar sequence
      NeuAcalpha2-3Galbeta1-3GalNAc. However, studies in our laboratory suggested a
      less restrictive binding epitope. LT-IIb(T13I), an LT-IIb variant, engineered by
      a single isoleucine-threonine substitution, retains biological activity, but with
      less robust inflammatory effects. We theorized that LT-IIb has a less restrictive
      binding epitope than previously proposed and that immunologic differences between
      LT-IIb and LT-IIb (T13I) correlate with subtle ganglioside binding differences.
      Ganglioside binding epitopes, determined by affinity overlay immunoblotting and
      enzymatic degradation of ganglioside components of RAW264.7 macrophages,
      indicated that LT-IIb bound to a broader array of gangliosides than previously
      recognized. Each possessed NeuAcalpha2-3Galbeta1-3GalNAc, although not
      necessarily as a terminal sequence. Rather, each had a requisite terminal or
      penultimate single sialic acid and binding was independent of ceramide
      composition. RAW264.7 enterotoxin-binding and non-binding ganglioside epitopes
      were definitively identified as GD1a and GM1a, respectively, by enzymatic
      degradation and mass spectroscopy. Affinity overlay immunoblots, constructed to
      the diverse array of known ganglioside structures of murine peritoneal
      macrophages, established that LT-IIb bound NeuAc- and NeuGc-gangliosides with
      nearly equal affinity. However, LT-IIb(T13I) exhibited enhanced affinity for
      NeuGc-gangliosides and more restrictive binding. These studies further elucidate
      the binding epitope for LT-IIb and suggest that the diminished inflammatory
      activity of LT-IIb(T13I) is mediated by a subtle shift in ganglioside binding.
      These studies underscore the high degree of specificity required for ganglioside
      protein interactions.

PMID- 19749204
TI  - Plasmid-borne blaSHV genes in Klebsiella pneumoniae are associated with strong
      promoters.
AB  - BACKGROUND: Extended-spectrum beta-lactamases (ESBLs) belonging to the SHV family
      remain a major cause of ESBL-positive phenotypes in Klebsiella pneumoniae. The
      bla(SHV) gene is a normal constituent of the K. pneumoniae chromosome. However,
      most ESBL-encoding bla(SHV) genes found in K. pneumoniae are plasmid borne. The
      objective was to determine the contribution of promoter variants to the
      expression of plasmid-borne bla(SHV) genes. METHODS: K. pneumoniae clinical
      isolates were analysed for the presence of IS26 insertions characteristic of
      plasmid-borne bla(SHV), and differences in their bla(SHV) promoter sequences and
      expression levels. A high resolution melting (HRM)-based method for rapid
      promoter analysis was developed. RESULTS: An IS26 insertion characteristic of the
      plasmid-borne bla(SHV-1)/bla(SHV-2)/bla(SHV-5) family was 100% linked to a
      promoter mutated in the -10 region, a mutation previously only found on the
      chromosome. The mutation was shown by real-time reverse transcriptase PCR to be
      associated with increased bla(SHV) expression. CONCLUSIONS: Plasmid-borne
      bla(SHV) is associated with strong promoters. It is likely that an SHV-dependent
      ESBL-positive phenotype requires both a strong promoter and a coding sequence
      mutation. An HRM assay can indicate bla(SHV) expression.

PMID- 19749205
TI  - Membrane sterol depletion impairs miltefosine action in wild-type and miltefosine
      resistant Leishmania donovani promastigotes.
AB  - OBJECTIVES: This study focuses on the importance of sterols in the action of
      miltefosine (hexadecylphosphocholine, HePC) against Leishmania donovani. METHODS:
      Plasma membranes of L. donovani promastigotes were depleted of sterol using
      methyl-beta-cyclodextrin (MCD) and cholesterol oxidase (CH-OX). Sterols were
      quantified and HePC susceptibility was assessed using the MTT test. A biomimetic
      model of the outer leaflet of a Leishmania plasma membrane was used to decipher
      the HePC-lipid interactions. RESULTS: CH-OX, which is known to act more
      specifically on condensed membranes, therefore at the level of lipid rafts, gave
      a better extraction yield in HePC-resistant parasites, confirming the more rigid
      structure of their membranes than those of wild-type parasites. Sterol depletion
      was responsible for a 40% decrease in HePC susceptibility in both wild-type and
      HePC-resistant parasites. Sterol repletion of the sterol-depleted parasites
      restored HePC susceptibility. The biomimetic model of the outer leaflet of a
      Leishmania plasma membrane confirmed that condensed microdomains were able to
      incorporate higher quantities of HePC than fluid ones and this result was
      amplified when the sterol concentration was increased. CONCLUSIONS: Sterol and
      lipid rafts probably play a significant role as an HePC reservoir providing a
      constant supply to the previously described transporter. In addition, (1)H NMR
      experiments suggested that HePC stimulated lipid trafficking in parasites.

PMID- 19749206
TI  - Idiopathic haemorrhagic diathesis diagnosed in calves across England.

PMID- 19749207
TI  - Noise levels in lairages for cattle, sheep and pigs in abattoirs in England and
      Wales.
AB  - Levels of sound intensity were measured over periods of 24 hours in 34 abattoir
      lairages in England and Wales. The mean integrated range in 12 cattle lairages
      was 52 to 79 dB(A), in 11 sheep lairages, 45 to 76 dB(A) and in 11 pig lairages,
      46 to 87 dB(A). In general, the pig lairages were the noisiest, with spot peak
      recordings of up to 110 dB(A). Typically, the sound intensities in all the
      lairages were 10 to 20 dB(A) higher during the working day than at night. In many
      sheep lairages, high intensities of sound were recorded frequently throughout the
      night, but others were very quiet, below 40 dB(A). Vocalisations were the major
      sources of noise in the pig and cattle lairages, but there were variations
      between them. There were high intensities of sound from handling systems (80 to
      90 dB[A]), and ventilating fans (70 to 80 dB[A]).

PMID- 19749208
TI  - Innervation of canine skin: an immunohistochemical study.
AB  - The general appearance of the innervation of samples of skin from 10 young
      beagles was studied by using the pan-neuronal immunolabel PGP9.5, and
      quantitative data on the density of the nerve fibres was obtained. The data
      provide a baseline for the development of a diagnostic test for small fibre
      neuropathy in domestic dogs.

PMID- 19749209
TI  - Identification of Mycoplasma bovigenitalium and Mycoplasma canadense from
      outbreaks of granulopapular vulvovaginitis in dairy cattle in Israel.
AB  - A syndrome in which white foci and granulopustular lesions appeared on the
      vaginal mucous membranes of Holstein cows in several dairy herds in Israel is
      described. During clinical and diagnostic investigations, Mycoplasma
      bovigenitalium was isolated from 11 of 20 clinical cases. Vaginal swabs taken
      from the same cows yielded three isolates of Mycoplasma canadense, which were all
      associated with the M bovigenitalium infection. Two isolates of small, round, non
      enveloped viral particles were approximately 25 nm in diameter and characteristic
      of enteroviruses on negative-staining electron microscopy.

PMID- 19749210
TI  - Use of serological techniques for diagnosis of Mycobacterium bovis infection in a
      llama herd.

PMID- 19749211
TI  - Chronic rhinitis secondary to the intrusion of a tooth into the nasal cavity of a
      cat.

PMID- 19749212
TI  - Proposed veterinary union.

PMID- 19749213
TI  - Method for rapid detection of swine influenza virus.

PMID- 19749214
TI  - Inflammatory pseudotumor of the trigeminal nerve: a neoplastic mimic you do not
      want to miss.
AB  - Inflammatory pseudotumor is a rare non-neoplastic mass that may clinically and
      radiologically mimic a spectrum of benign and malignant neoplasms. It is uncommon
      in the head and neck and particularly rare at the skull base. We present a case
      of pseudotumor originating from the trigeminal nerve in a patient who presented
      with headache and facial numbness. A high index of suspicion is necessary to
      diagnose this benign but locally aggressive entity.

PMID- 19749215
TI  - The use of Onyx for embolization of central nervous system arteriovenous lesions
      in pediatric patients.
AB  - BACKGROUND AND PURPOSE: The safety and efficacy of Onyx for the embolization of
      central nervous system (CNS) arteriovenous (AV) lesions have been widely reported
      in adults. However, data describing the use of this agent in children are
      limited. This study presents our experience with Onyx in the treatment of CNS AV
      lesions in pediatric patients. MATERIALS AND METHODS: We retrospectively analyzed
      clinical and imaging records of 15 pediatric patients who underwent 36
      transarterial embolizations by using Onyx for CNS AV lesions, from March 2007
      through April 2009 at our institution. Underlying pathologies included brain AV
      malformations (AVMs) (n = 7), vein of Galen malformations (n = 4), dural AV
      fistulas (n = 2), and spinal AVMs (n = 2). For 7 procedures in very high-flow
      lesions, detachable coils were deployed before Onyx embolization, whereas in 29
      procedures, Onyx was the sole embolic agent. The efficacy of embolization was
      judged by the residuum of AV shunting within the target region. RESULTS:
      Embolization was complete in 2 patients, nearly complete in 9 patients, and
      partial (and ongoing) in 4 patients. Following staged embolization, 7 patients
      underwent surgical resection without significant blood loss and with good
      functional outcome in all cases. Clinically silent non-target embolization was
      encountered in 2 of 36 procedures. After 3 of the 36 embolizations, patients
      developed transient neurologic symptoms, all of which resolved to baseline within
      24 hours. There were no non-neurologic adverse events. There was no imaging
      evidence of infarct or hemorrhage. CONCLUSIONS: Onyx embolization of pediatric
      CNS AV lesions can be an efficacious treatment technique, with extremely low
      associated morbidity.

PMID- 19749216
TI  - Carotid artery stents: in vitro comparison of different stent designs and sizes
      using CT angiography and contrast-enhanced MR angiography at 1.5T and 3T.
AB  - BACKGROUND AND PURPOSE: CT angiography (CTA) and MR angiography (MRA) are
      increasingly used methods for evaluation of stented vessel segments. Our aim was
      to compare CTA, contrast-enhanced MRA (CE-MRA) at 1.5T, and CE-MRA at 3T for the
      visualization of carotid artery stents and to define the best noninvasive imaging
      technique as an alternative to conventional angiography for each stent. MATERIALS
      AND METHODS: CTA and CE-MRA appearances of 18 carotid artery stents of different
      designs and sizes (4.0 to 10.0 mm) were investigated in vitro. For each stent,
      artificial lumen narrowing (ALN) was calculated. RESULTS: With CE-MRA at 3T and
      at 1.5T, ALN in most nitinol stents was lower than that in the groups of
      stainless steel and cobalt alloy stents. In most nitinol stents and in both
      cobalt alloy stents, ALN was lower on CE-MRA at 3T than at 1.5T. In all stainless
      steel stents, ALN was lower on CTA than on CE-MRA. With CTA and CE-MRA, in most
      stents ALN decreased with increasing stent diameter. CONCLUSIONS: CTA and CE-MRA
      evaluation of vessel patency after stent placement is possible but is
      considerably impaired by ALN. Investigators should be informed about the method
      of choice for every stent. Stent manufacturers should be aware of potential
      artifacts caused by their stents during noninvasive diagnostic methods such as
      CTA and CE-MRA.

PMID- 19749217
TI  - Enhanced detection of diffusion reductions in Creutzfeldt-Jakob disease at a
      higher B factor.
AB  - BACKGROUND AND PURPOSE: Diffusion-weighted imaging (DWI) is sensitive to the
      cerebral manifestations of human prion diseases. The magnitude of diffusion
      weighting, termed "b factor," has only been evaluated at the standard b = 1000
      s/mm(2). This is the first rigorous evaluation of b = 2000 s/mm(2) in Creutzfeldt
      Jakob Disease (CJD). MATERIALS AND METHODS: We compared DWI characteristics of 13
      patients with CJD and 15 healthy controls at b = 1000 s/mm(2) and b = 2000
      s/mm(2). Apparent diffusion coefficients (ADC) were computed and analyzed for the
      whole brain by voxel-wise analysis (by SPM5) as well as in anatomically defined
      volumes of interest (by FSL FIRST). RESULTS: Measured ADC was significantly lower
      (by approximately 5%-15%) at b = 2000 s/mm(2) than at b = 1000 s/mm(2) and
      significantly lower in patients than in controls. The differences between
      patients and controls were greater and more extensive at b = 2000 s/mm(2) than at
      b = 1000 s/mm(2) in the expected regions (thalamus, putamen, and caudate
      nucleus). CONCLUSIONS: Because higher b factors change the absolute value of
      observed ADC, as well as lesion detection, care should be taken when combining
      studies using different b factors. While the clinical application of high b
      factors is currently limited by a low signal intensity-to-noise ratio, it may
      offer more information in questionable cases, and our results confirm and extend
      the central role of diffusion imaging in human prion diseases.

PMID- 19749218
TI  - Endovascular coil embolization of aneurysms with a branch incorporated into the
      sac.
AB  - BACKGROUND AND PURPOSE: Because of the concern for occlusion of the incorporated
      branch artery, an aneurysm with a branch incorporated into the sac has been
      regarded as a contraindication for coiling. The aim of this study is to evaluate
      the feasibility, techniques, and clinical and angiographic outcomes of coiling
      for aneurysms with a branch incorporated into the sac. MATERIALS AND METHODS: The
      medical records and radiologic studies of 69 patients with 79 aneurysms having a
      branch incorporated into the sac (26 ruptured, 53 unruptured) were
      retrospectively reviewed and evaluated. RESULTS: Coiling was accomplished in 78
      aneurysms in 68 patients but was suspended in 1 due to incorporated branch
      occlusion. The aneurysms were treated by using the following techniques: single
      catheter (n = 37), multicatheter (n = 22), balloon-remodeling (n = 7), stent
      assisted coiling (n = 6), and combined (n = 7). Postembolization angiography
      revealed the following: near-complete occlusion in 71 (89.8%), remnant neck in 4
      (5.1%), and incomplete occlusion in 4 (5.1%) aneurysms. Procedure-related
      permanent morbidity and mortality rates were 5.8% (4/69) and 0%, respectively.
      All patients with unruptured aneurysms had a modified Rankin Scale (mRS) score of
      0, except for 1 patient who had an mRS score of 3. Of the 26 patients with
      ruptured aneurysms, 18 had favorable outcome (mRS 0-2) but 8 had poor outcome
      (mRS 3-6). Follow-up angiography was available at least once at 6-50 months
      (mean, 15 months) in 55 aneurysms (69.6%), of which 45 showed stable or improved
      occlusion; 4, minor recurrences; and 6, major recurrences. All 6 major recurrent
      aneurysms were retreated without complication by using a single-catheter (n = 1),
      multicatheter (n = 2), or balloon-assisted technique (n = 3). CONCLUSIONS: With
      appropriate techniques, most aneurysms with a branch incorporated into the sac
      could be safely treated by coiling, with acceptable outcomes.

PMID- 19749219
TI  - Mild hypoxic-ischemic injury in the neonatal rat brain: longitudinal evaluation
      of white matter using diffusion tensor MR imaging.
AB  - BACKGROUND AND PURPOSE: Selective white matter (WM) damage is a known sequela of
      mild hypoxic-ischemic (HI) injury in the neonatal rat model. The aim of this
      study was to evaluate longitudinally mild HI-induced WM damage (represented by
      the external capsule [EC]) by diffusion tensor MR imaging (DTI) and to correlate
      the findings with histology. MATERIALS AND METHODS: Seven-day-old Sprague-Dawley
      rats (n = 19) underwent unilateral ligation of the left common carotid artery
      followed by hypoxia for 50 minutes to create mild HI injury. DTI was performed
      longitudinally at 5 time points from day 1 to day 90 postinjury (n = 19, 16, 13,
      11, 9, respectively), and fractional anisotropy (FA), trace, radial diffusivity
      (lambda( perpendicular)), and axial diffusivity (lambda(//)) of the injury and
      control contralateral ECs were quantified. Rats were randomly sacrificed (n = 15,
      in total), and the corresponding ECs were stained with hematoxylin-eosin, Luxol
      fast blue (LFB), and neurofilament (NF) to evaluate morphologic changes, amount
      of myelin, and axonal count at every time point. A paired t test was applied to
      evaluate statistical differences between both ECs, and the Pearson correlation
      test was used to evaluate the relationships between DTI indices and histologic
      evaluations. In addition, longitudinal changes in DTI indices and histologic
      evaluations were analyzed by a linear mixed model and an analysis of variance
      test, respectively. RESULTS: We demonstrated significantly decreased FA,
      increased lambda( perpendicular), and similar lambda(//) in the injury compared
      with the control EC, which was persistent through all time points. Histologic
      evaluation by LFB and NF staining showed reduced myelin stain intensity in the
      injury EC and similar axonal counts in both ECs. Longitudinally, there was an
      increase in FA, a decrease in lambda( perpendicular) and trace, and stability in
      lambda(//) in both ECs. Also, there was progressive reduction in the differences
      in FA, trace, and lambda( perpendicular) between the injury and control EC,
      especially between day 1 and day 7 postinjury and in tandem with changes in
      myelin stain. FA was significantly correlated with myelin stain (r = 0.681, P <
      .01) and axonal count (r = 0.673, P < .01), whereas lambda( perpendicular) was
      significantly correlated with myelin stain only (r = -0.528, P < .01), and
      lambda(//), with axonal count only (r = 0.372, P = .043). CONCLUSIONS: Diffusion
      indices can reflect dysmyelination in mild HI injury, continual myelination of
      both injury and control ECs with growth, and the partial recovery of myelin
      postinjury. We propose that diffusion indices may be used as biomarkers to
      monitor noninvasively the longitudinal changes of mild HI-induced WM damage.

PMID- 19749220
TI  - Balloon-related complications and technical failures in kyphoplasty for vertebral
      fractures.
AB  - BACKGROUND AND PURPOSE: Our aim was to describe the immediate or early
      complications and technical failures occurring during balloon kyphoplasty (BKP)
      procedures and attributable to balloon inflation. MATERIALS AND METHODS: We
      performed a retrospective review of all consecutive kyphoplasty procedures
      performed in our institution from May 2005 to October 2006. Fifty-one patients
      were treated by BKP at 75 spinal levels, and 137 vertebroplasties were performed
      as well. RESULTS: Several recurrent complications or procedural failures were
      observed during BKP: cortical or endplate fracture by balloon expansion (4
      vertebrae), partial vertebral re-collapse after deflation (4 vertebrae), balloon
      rupture during inflation (5 vertebrae), and transient hyperalgia after the
      procedure (11 patients, 27.5%). CONCLUSIONS: Several symptomatic or asymptomatic
      complications and technical failures can occur during BKP. Some modifications of
      the usual kyphoplasty technique may decrease the frequency of these
      complications.

PMID- 19749221
TI  - Do iodinated contrast agents impair fibrinolysis in acute stroke? A systematic
      review.
AB  - BACKGROUND AND PURPOSE: In vitro and nonhuman in vivo studies demonstrating
      impaired fibrinolysis of thrombus by thrombolytic agents in the presence of
      iodinated contrast media (ICM) have prompted concern regarding the clinical use
      of ICM. A systematic review and meta-analysis were performed to investigate the
      proportion of patients with acute stroke experiencing recanalization after
      thrombolytic therapy in whom ICM were administered compared with those in whom
      they were not. MATERIALS AND METHODS: Embase and Medline searches identified
      studies reporting recanalization rates in acute ischemic anterior circulation
      stroke. Pooled proportions of patients who recanalized were calculated with a
      random-effects model, and studies involving contrast (CS) were compared with
      those without (NCS). RESULTS: Six studies were found in which ICM were
      administered, and 12 studies, in which they were not. Studies were statistically
      heterogeneous. Combined pooled proportions and 95% confidence intervals (CI) for
      recanalization in unselected CS and NCS were 53% (36%-70%) and 61% (52%-71%),
      respectively. In a subgroup analysis in which only middle cerebral artery
      occlusions were considered, the pooled proportions in CS (n = 3 studies) and NCS
      (n = 9 studies) were 66% (95% CI, 49%-82%; I(2), 0%) and 63% (CI, 52%-74%; I(2),
      82.5%). CONCLUSIONS: Recanalization rates were not significantly different in
      patients who received iodinated contrast agents in clinical studies. A randomized
      trial to test whether ICM affect recanalization would require a prohibitively
      large number of subjects.

PMID- 19749222
TI  - Decreased left posterior insular activity during auditory language in autism.
AB  - BACKGROUND AND PURPOSE: Individuals with autism spectrum disorders often exhibit
      atypical language patterns, including delay of speech onset, literal speech
      interpretation, and poor recognition of social and emotional cues in speech. We
      acquired functional MR images during an auditory language task to evaluate
      systematic differences in language-network activation between control and high
      functioning autistic populations. MATERIALS AND METHODS: Forty-one right-handed
      male subjects (26 high-functioning autistic subjects, 15 controls) were studied
      by using an auditory phrase-recognition task, and areas of differential
      activation between groups were identified. Hand preference, verbal intelligence
      quotient (IQ), age, and language-function testing were included as covariables in
      the analysis. RESULTS: Control and autistic subjects showed similar language
      activation networks, with 2 notable differences. Control subjects showed
      significantly increased activation in the left posterior insula compared with
      autistic subjects (P < .05, false discovery rate), and autistic subjects showed
      increased bilaterality of receptive language compared with control subjects.
      Higher receptive-language scores on standardized testing were associated with
      greater activation of the posterior aspect of the left Wernicke area. A higher
      verbal IQ was associated with greater activation of the bilateral Broca area and
      involvement of the prefrontal cortex and lateral premotor cortex. CONCLUSIONS:
      Control subjects showed greater activation of the posterior insula during
      receptive language, which may correlate with impaired emotive processing of
      language in autism. Subjects with autism showed greater bilateral activation of
      receptive-language areas, which was out of proportion to the differences in hand
      preference in autism and control populations.

PMID- 19749223
TI  - Optimized preload leakage-correction methods to improve the diagnostic accuracy
      of dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging in
      posttreatment gliomas.
AB  - BACKGROUND AND PURPOSE: Relative cerebral blood volume (rCBV) accuracy can vary
      substantially depending on the dynamic susceptibility-weighted contrast-enhanced
      (DSC) acquisition and postprocessing methods, due to blood-brain barrier
      disruption and resulting T1-weighted leakage and T2- and/or T2*-weighted imaging
      (T2/T2*WI) residual effects. We set out to determine optimal DSC conditions that
      address these errors and maximize rCBV accuracy in differentiating posttreatment
      radiation effect (PTRE) and tumor. MATERIALS AND METHODS: We recruited patients
      with previously treated high-grade gliomas undergoing image-guided re-resection
      of recurrent contrast-enhancing MR imaging lesions. Thirty-six surgical tissue
      samples were collected from 11 subjects. Preoperative 3T DSC used 6 sequential
      evenly timed acquisitions, each by using a 0.05-mmol/kg gadodiamide bolus.
      Preload dosing (PLD) and baseline subtraction (BLS) techniques corrected T1
      weighted leakage and T2/T2*WI residual effects, respectively. PLD amount and
      incubation time increased with each sequential acquisition. Corresponding tissue
      specimen stereotactic locations were coregistered to DSC to measure localized
      rCBV under varying PLD amounts, incubation times, and the presence of BLS. rCBV
      thresholds were determined to maximize test accuracy (average of sensitivity and
      specificity) in distinguishing tumor (n = 21) and PTRE (n = 15) samples under the
      varying conditions. Receiver operator characteristic (ROC) areas under the curve
      (AUCs) were statistically compared. RESULTS: The protocol that combined PLD (0.1
      mmol/kg amount, 6-minute incubation time) and BLS correction methods maximized
      test AUC (0.99) and accuracy (95.2%) compared with uncorrected rCBV AUC (0.85)
      and accuracy (81.0%) measured without PLD and BLS (P = .01). CONCLUSIONS:
      Combining PLD and BLS correction methods for T1-weighted and T2/T2*WI errors,
      respectively, enables highly accurate differentiation of PTRE and tumor growth.

PMID- 19749224
TI  - Diffuse white matter damage is absent in neuromyelitis optica.
AB  - BACKGROUND AND PURPOSE: Neuromyelitis optica (NMO) is an idiopathic mostly
      relapsing inflammatory disease with attacks on the optic nerves and spinal cord.
      Whether NMO is a separate disease or a subtype of classic multiple sclerosis (MS)
      is unclear. Clinically, CSF and MR imaging parameters and histopathologic data
      suggest that the normal-appearing white matter (NAWM) may be affected in MS but
      not in patients with NMO. Therefore, we hypothesized that the NAWM in NMO is
      normal. MATERIAL AND METHODS: We studied prospectively 8 patients with clinically
      definitive NMO or remitting longitudinal extensive transverse myelitis (LETM) and
      8 healthy controls. Ratios of N-acetylaspartate to creatine (Cr) and choline to
      Cr and the absolute concentrations of the metabolites were measured by chemical
      shift imaging with a (1)H-MR spectroscopy operating at 3T. All patients with
      clinically definitive NMO and LETM were found to be positive for NMO-immunoglobin
      G with a commercially available test. RESULTS: The metabolic pattern of the NAWM
      of patients with NMO showed no difference compared with age- and sex-matched
      healthy controls. CONCLUSIONS: Diffuse white matter damage is absent in NMO.

PMID- 19749225
TI  - Neuroimaging and deep brain stimulation.
AB  - Deep brain stimulation (DBS) is a new neurosurgical method principally used for
      the treatment of Parkinson disease (PD). Many new applications of DBS are under
      development, including the treatment of intractable psychiatric diseases. Brain
      imaging is used for the selection of patients for DBS, to localize the target
      nucleus, to detect complications, and to evaluate the final electrode contact
      position. In patients with implanted DBS systems, there is a risk of electrode
      heating when MR imaging is performed. This contraindicates MR imaging unless
      specific precautions are taken. Involvement of neuroradiologists in DBS
      procedures is essential to optimize presurgical evaluation, targeting, and
      postoperative anatomic results. The precision of the neuroradiologic correlation
      with anatomic data and clinical outcomes in DBS promises to yield significant
      basic science and clinical advances in the future.

PMID- 19749226
TI  - Reconstructive endovascular treatment of intracranial fusiform aneurysms: a 1
      stage procedure with stent and balloon.
AB  - BACKGROUND AND PURPOSE: Intracranial fusiform aneurysms, which incorporate the
      branch vessel and require salvaging of the parent vessel, are difficult to
      manage. The goal of this study was to evaluate the efficacy of reconstructive
      endovascular treatment of intracranial fusiform aneurysms by using a 1-stage
      procedure with a stent and balloon. MATERIALS AND METHODS: During a 3-year
      period, 20 patients with 20 intracranial fusiform aneurysms were treated by using
      a 1-stage procedure involving a balloon and stent. Subarachnoid hemorrhage was
      present in 15 patients. Five aneurysms were located in the anterior circulation
      and 15, in the posterior circulation. Clinical outcomes and periprocedural
      complications were evaluated in all patients. The extent of coil packing was
      evaluated by control angiography after embolization and classified as either
      complete occlusion or partial occlusion. Angiography was performed 6, 12, and 24
      months after embolization to evaluate stent patency and coil packing. RESULTS:
      The 1-stage procedure by using a combination of balloon and stent was technically
      successful in all patients. There were no complications related to the procedure,
      complete occlusion was obtained in 16 patients, and partial occlusion, in 4
      patients. All patients recovered well except for 2 who died due to causes
      unrelated to the procedure. Clinical follow-up was performed in all surviving
      patients at a mean of 12.3 months (range, 7-24 months), and angiography showed
      that the patent parent arteries were free of aneurysm recanalization or in-stent
      stenosis. CONCLUSIONS: This 1-stage procedure may provide a feasible and safe
      treatment strategy for the management of intracranial fusiform aneurysms that are
      not amenable to deconstructive embolization.

PMID- 19749227
TI  - Intrinsic pathway-mediated apoptosis in elastase-induced aneurysms in rabbits.
AB  - BACKGROUND AND OBJECTIVES: The pathophysiology of saccular aneurysms is complex
      and multifactorial. The aim of the present study was to understand the mechanism
      of apoptosis in an elastase-induced aneurysm model in rabbits. MATERIALS AND
      METHODS: Elastase-induced saccular aneurysms were created at the origin of the
      right common carotid artery in 20 rabbits. Aneurysm samples were harvested at 2
      and 12 weeks after creation. Expression of apoptosis-associated proteins,
      including caspases and bcl-2 proteins, were assessed by Western blot analysis (n
      = 5 at both time points). Terminal deoxynucleotidyltransferase-mediated dUTP nick
      end-labeling (TUNEL) staining, which indicates the presence of apoptosis, was
      performed in tissue sections (n = 5 at both time points). The unoperated
      contralateral common carotid artery was used as a control. RESULTS: Expression of
      active caspase-3, the final executioner of apoptosis, and caspase-9, the mediator
      of the intrinsic mitochondrial pathway, was observed in aneurysms at 2 weeks,
      whereas the expression of activated caspase-8, the mediator of the extrinsic
      death receptor pathway, was absent at both time points. Expression of
      antiapoptotic proteins, Bcl-2 and phospho-Bad, was down-regulated in aneurysms
      compared with controls at 2 weeks. None of these proteins were differentially
      expressed at 12 weeks. These results were confirmed by the presence of TUNEL
      positive cells in some aneurysms at the early time point. CONCLUSIONS: In this
      study of elastase-induced aneurysms in a rabbit model, activation of apoptosis is
      mediated predominantly by the Bcl-2-mediated intrinsic pathway through the
      activation of caspase-9.

PMID- 19749230
TI  - Reaction of the 4'-benzenesulfonyl derivatives of thymidine with organosilicon
      and organoaluminum reagents.
AB  - With an aim to develop a new approach to synthesize 4'-substituted nucleosides,
      reactions of thymidine derivatives having a benzenesulfonyl leaving group at the
      4'-position with organosilicon and organoaluminum reagents were investigated. Two
      substrates 4alpha (alpha-L-isomer) and 4 beta (beta-D-isomer) were prepared for
      this purpose. Although reaction of 4alpha with organosilicon reagents gave
      preferentially the 4'-substituted (allyl and N(3)) beta-D-nucleoside, its
      reaction with AlMe(3) gave the 4'-methyl-alpha-L-thymidine as the major product.
      On the other hand, the substrate 4beta, upon reacting with AlMe(3), furnished the
      desired 4'-methylthymidine exclusively in high yield.

PMID- 19749231
TI  - Alternative I-D exchange reaction on pyrimidine and purine nuclei mediated by
      tributyltin hydride using THF-d8 as a deuterium source.
AB  - A novel method for the regioselective deuteration of pyrimidine and purine rings
      mediated by Bu(3)SnH using THF-d(8) as a deuterium source on the basis of a
      radical reaction was developed.

PMID- 19749232
TI  - Rational design and synthesis of ansa-adenosines as potential antitumor agents.
AB  - Synthesis of benzoquinone ansa-adenosines, which are rationally designed as Hsp90
      inhibitors by extracting and fusing a natural substrate, ATP, and a natural
      product, geldanamycin, was described. This simpler scaffold design provides
      practical synthesis of a set of analogs and demonstrates synthetic innovation.

PMID- 19749233
TI  - Development of next generation 4'-selenonucleosides.
AB  - Next generation 4'-selenonucleosides as potential antiviral and antitumor agents
      were synthesized using a Pummerer type condensation as a key step.

PMID- 19749234
TI  - Stereocontrolled synthesis of oligodeoxyribonucleoside boranophosphates via
      stereodefined H-phosphonate intermediates.
AB  - P-Stereodefined oligodeoxyribonucleoside boranophosphates (PB-ODNs) were
      successfully synthesized by the conversion of diastereopure H-phosphonate
      intermediates. Thermal denaturation studies clearly showed that the duplex
      stability of PB-ODNs with the complementary DNA and RNA depends on the
      stereochemistry of the boranophosphate linkages.

PMID- 19749235
TI  - Synthesis and properties of a novel 2',4'-BNA bearing a urea bridged structure.
AB  - Three kinds of novel bridged nucleic acid (BNA) monomers bearing carbamate or
      urea bridged structures, were designed and synthesized. One of these monomers, a
      urea-type BNA monomer was successfully incorporated into oligodeoxynucleotides
      (ODNs), and properties of the ODNs were evaluated. The ODNs containing the urea
      type BNA monomers showed RNA selective hybridizing profiles and significant
      enzymatic stability.

PMID- 19749236
TI  - Synthesis and properties of terminally modified oligonucleotides capable of short
      RNA selective hybridization.
AB  - We have developed 2'-O-methyl-RNAs having phosphorylated cyclohexane at the 5'
      and/or 3'-terminal adenine. These 2'-O-methyl-RNAs formed less stable duplex with
      the longer target RNA than that with the short target RNA. We tried to improve
      the short-RNA selective hybridization property by the synthesis of 2'-O-methyl
      RNAs having terminal guanine modifications.

PMID- 19749237
TI  - Biochemical dissection of RISC assembly and function.
AB  - Small silencing RNAs, including small interfering RNAs (siRNAs) and microRNAs
      (miRNAs), regulate expression of their target genes via RNA-induced silencing
      complex (RISC). RISC assembly follows complex, ordered pathways, and RISC
      function is as diverse as cleavage, translational repression, and deadenylation
      of the target. We have recently shown how siRNAs and miRNAs are assembled into
      distinct types of RISC, and how differently they function, using Drosophila as a
      model organism.

PMID- 19749238
TI  - Metal ion binding of modified pyrimidine-base pairs in DNA duplexes.
AB  - We report the synthesis and metal ion-binding properties of DNA duplexes
      containing 5-substituted uracil ((X)U) pairs, such as 5-bromouracil, 5
      fluorouracil and 5-cyanouracil pairs. Thermal denaturation studies of these
      modified DNA duplexes revealed that the DNA duplexes were stabilized in the
      presence of Hg(II) ions in acidic and neutral solutions. On the other hand, the
      duplexes were stabilized in the presence of Hg(II) and Ag(I) ions. These results
      indicated that (X)U-Hg(II)-(X)U complex was formed in the acidic and neutral
      solutions, then, in the basic solutions (X)U-Ag(I)-(X)U complex as well as the
      (X)U-Hg(II)-(X)U complex were formed. ESI-TOF MS analysis also indicated
      formation of the metal ion-DNA complexes.

PMID- 19749239
TI  - Interaction of silver ion with CG.C+ base triplets in DNA triplex.
AB  - When designing ligands for specific sequences in DNA duplexes, triple helix
      formation is a useful recognition motif, because base triplet formation is based
      on the simple rule of complementary Hoogsteen hydrogen bonding, CG.C(+) and TA.T.
      However the triplexes containing CG.C(+) triplets form only in a weak acidic
      solution, because cytosines in third strand need to be protonated to satisfy its
      complementarity to CG base-pairs. A simple and easy method to stabilize the DNA
      triplex using Ag(+) was reported. A silver ion displaces the N3 proton of
      cytosine in Hoogsteen base-pairing to form a base triplet, CG.CAg(+). By the
      addition of an equimolar amount of Ag(+), the third strand 15 mer sequence
      containing five cytosines was stabilized by ca. 30 degrees C in melting
      temperature at pH 7. The triplex structure was stable even under weak basic
      conditions.

PMID- 19749240
TI  - Synthesis and triplex formation of oligonucleotides containing 8
      thioxodeoxyadenosine and 5-methyl-2-thiodeoxycytosine.
AB  - For more effective DNA triplex formation under neutral conditions, we synthesized
      triplex-forming oligonucleotides (TFO) containing 8-thioxodeoxyadenine (s(8)A)
      residues in place of the protonated cytosines (Cs) required for the third base
      pairing with DNA duplexes. Consequently, it was found that s(8)A exhibited much
      stronger hybridization ability than C under neutral conditions when four s(8)A
      bases were arranged in a consecutive sequence. Moreover, we also synthesized TFOs
      containing 5-methyl-2-thiocytosines and examined their ability of triplex
      formation.

PMID- 19749241
TI  - Development of a novel device to trap heavy metal cations: application of the
      specific interaction between heavy metal cation and mismatch DNA base pair.
AB  - We have already found that Hg(II) cation specifically binds to T:T mismatch base
      pair in heteroduplex DNA, which increases the melting temperature of heteroduplex
      DNA involving T:T mismatch base pair by about 4 degrees C. We have also found
      that Ag(I) cation specifically binds to C:C mismatch base pair in heteroduplex
      DNA, which increases the melting temperature of heteroduplex DNA involving C:C
      mismatch base pair by about 4 degrees C. Using the specific interaction, we
      developed a novel device to trap each of Hg(II) and Ag(I) cation. The device is
      composed of 5'-biotinylated T-rich or C-rich DNA oligonucleotides, BIO-T20: 5'
      Bio-T(20)-3' or BIO-C20: 5'-Bio-C(20)-3' (Bio is a biotin), immobilized on
      streptavidin-coated polystylene beads. When the BIO-T20-immobilized beads were
      added to a solution containing Hg(II) cation, and the beads trapping Hg(II)
      cation were collected by centrifugation, almost all of Hg(II) cation were removed
      from the solution. Also, when the BIO-C20-immobilized beads were added to a
      solution containing Ag(I) cation, and the beads trapping Ag(I) cation were
      collected by centrifugation, almost all of Ag(I) cation were removed from the
      solution. We conclude that, using the novel device developed in this study,
      Hg(II) and Ag(I) cation can be effectively removed from the solution.

PMID- 19749243
TI  - Synthesis and properties of oligodeoxynucleotides containing biaryl units.
AB  - We describe the synthesis and properties of oligonucleotides (ONs) containing
      biaryl units, which are composed of a bis(hydroxymethyl)benzene residue and a
      naphthalene or pyrene moiety. We found that by introducing the biaryl units into
      the ONs, the aromatic chromophores are suitably arrayed in the DNAs. Further, we
      succeeded in the detection of a single-base mismatch in RNA by using the ON
      containing the biaryl unit as a molecular beacon.

PMID- 19749244
TI  - Efficient energy transfer from pyrene to perylene assembled inside DNA duplex.
AB  - Pyrene (donor) and perylene (acceptor) were assembled in a DNA duplex to increase
      the apparent Stokes' shift of perylene. Multiple donors were introduced in the
      vicinity of acceptors via D-threoninol and natural base pairs were inserted
      between donors and acceptors in order to suppress undesired interactions between
      them. When two pyrene moieties were located in proximity to one perylene with one
      base pair inserted between them, efficient FRET occurred within the duplex. Thus,
      strong emission at 495 nm was observed from perylene when excited at 345 nm where
      pyrene has its absorption. The apparent Stokes' shift became as large as 115 nm
      with a high FRET efficiency (Phi>1). However, the introduction of more than two
      pyrenes did not enhance the fluorescence intensity of perylene, due to the short
      Forster radius (R(0)) of the donor pyrene.

PMID- 19749245
TI  - Investigation of the mechanism of the fluorescent emission of the silylated
      pyrene modified DNA.
AB  - Modified DNA containing silylated pyrene derivative at the 5'-terminus showed the
      obvious discrimination ability of the duplex formation, that the modified DNA
      showed the strong fluorescence emission in the presence of the complementary DNA,
      in spite of the very weak emission in the absence of the complementary DNA. The
      intensity of the fluorescence emission of the double strand found to increase
      about 10 times compared with that of the single strand. In this paper, we tried
      to disclose the detailed mechanism of such a discrimination ability of the
      silylated pyrene-modified DNA.

PMID- 19749246
TI  - Toward a reciprocal evolution system between RNA and peptides as an artificial
      model for the early RNP world.
AB  - In the early stages of the evolution of life, RNA-polypeptide complexes (RNPs)
      have been suggested to play crucial roles. At a certain developmental stage of
      ancient RNPs, their RNA and polypeptide components could evolve in an
      interdependent manner to develop complex structures and functions. To mimic this
      possible process, we have designed an RNA molecule that can act as a template for
      chemical peptide ligation. This designed RNA possesses two peptide-binding sites
      that capture the two basic peptides. The designed RNA actually facilitated the
      peptide ligation. The resulting ligated peptide, which has two RNA binding sites,
      can in turn function as a trans-activator that enhances the intrinsic ribozymatic
      activity of the designed RNA.

PMID- 19749247
TI  - Substrate recognition of pre-tRNA by ribonuclease P---subsite model of natural
      ribozyme originated from Escherichia coli.
AB  - Combination of cleavage site analysis and kinetic analysis of a series of shape
      variant of pre-tRNA substrate, we newly found two subsites which contribute to
      recognition of shape in substrate binding and catalysis by bacterial RNase P. Our
      data showed that the ribozyme traps the substrate by 5'- and 3'-end regions to
      form Michaelis complex, and after that the shape of the substrate is examined by
      other two subsites in the transition state. In the meeting, we will show the
      possibility that the S-domain can contribute to stabilize the transition state of
      the cleavage reaction of a pre-tRNA substrate.

PMID- 19749248
TI  - The NEXT-A (N-terminal EXtension with Transferase and ARS) reaction.
AB  - L/F-transferase is known to catalyze transfer of hydrophobic amino acids from
      aminoacyl tRNA to the N-terminus of a protein possessing lysine or arginine as
      the N-terminus. Combining L/F-transferase with E. coli phenylalanyl-tRNA
      synthetase (ARS), we achieved non-ribosomal N-terminal-specific introduction of
      various kinds of nonnatural amino acids to a protein. A nonnatural amino acid is
      once charged onto an E. coli tRNA(Phe) by a mutant ARS in situ, and successively
      transferred from the tRNA to a target protein, namely the NEXT-A reaction.
      Besides alphaA294G mutation on the ARS, alphaT251A, betaG318W, or betaA356W
      double-mutation were effective to increase the introduction efficiency through
      the NEXT-A reaction. Protein specific fluorescence labelling via the NEXT-A
      reaction followed by Huisgen cycloaddition was also demonstrated.

PMID- 19749249
TI  - The exceptional properties of Plasmodium deoxyguanylate pathways as a potential
      area for metabolic and drug discovery studies.
AB  - In Plasmodium falciparum, deoxyguanylate was found to be a substrate for several
      DNA metabolizing enzymes. Guanylate kinase utilizes dGMP with very low
      specificity, which is estimated to be the lowest among well-known prokaryotic and
      eukaryotic enzymes. Furthermore, thymidylate kinase, which is a pyrimidine
      specific enzyme, was found to phosphorylate dGMP with a surprisingly high
      specificity similar to that of the natural substrate. The above mentioned
      distinctions are specific for the Plasmodium protozoa and provide an interesting
      method for tracking dGMP metabolism during development and a starting point for
      drug development.

PMID- 19749250
TI  - Structural basis for the specificity of thymidylate kinases from human pathogens:
      implications for nucleotide analogues activation.
AB  - Several human pathogens possess nucleoside or nucleotide kinases with large
      substrate specificity compared to their human counterparts. This phenomenon has
      been successfully exploited for the specific targeting of prodrugs such as
      Acyclovir against herpes virus. Combined structural and biochemical studies of
      these enzymes can thus provide essential information for the rational design of
      specific antimicrobial agents. Here we studied the structural basis for the
      specificity of a thymidylate kinase from the poxvirus family. Poxvirus
      thymidylate kinase has unusual substrate specificity and can accept bulky
      analogues such as 5-bromo-vinyl-dUMP (BVdUMP). The 2 A crystal structure of the
      thymidylate kinase bound to this compound now gives the structural basis for its
      specific molecular recognition.

PMID- 19749251
TI  - Chemical methods to study protein-nucleic acid interactions.
AB  - Accumulation of genetic changes due to the presence of unrepaired DNA lesions can
      lead to cancer development and other diseases. Nucleic acid modifications also
      play key roles in many essential life processes. We have developed a series of
      chemically modified nucleic acid analogues that can be applied to stabilize
      protein-nucleic acid interactions for structural and proteomic studies. Some of
      the probes have also been employed to study nucleic acid-nucleic acid
      interactions.

PMID- 19749252
TI  - Development of novel chemical probes to detect abasic sites in DNA.
AB  - We chemically synthesized a series of aminooxy derivatives to develop novel
      probes for sensitive detection of abasic (AP) sites in DNA. The results of the
      conjugation reactions showed that the probes could efficiently react to AP sites
      by introducing an aromatic or a guanidino group in their structures. In
      particular, the probe having both functional groups showed the most effective
      reactivity, indicating that hydrophobic and electrostatic interactions
      cooperatively acted in the reaction of the probe to AP sites. We then synthesized
      a biotinylated probe and succeeded in more sensitive detection of AP sites in
      genomic DNA than with the conventional aldehyde reactive probe (ARP).

PMID- 19749253
TI  - Assessment of the DNA damage using the fluorescence microscope.
AB  - DNA damage was monitored by fluorescent microscopy observations of DNA
      fluorescent images after hydrodynamic stretching on a microscope glass. DNA
      double-strand breaks lead to a decrease of the average length of observed
      fluorescent DNA molecules. Compared to conventional methods such as
      electrophoresis, the proposed method allows for the analysis of the DNA damage at
      very low DNA breaking frequency. In particular, this method was used to study DNA
      damage by weak UV irradiation in solutions of quantum dots.

PMID- 19749254
TI  - Exciton-controlled fluorescence: application to hybridization-sensitive
      fluorescent DNA probe.
AB  - A hybridization-sensitive fluorescent probe has been designed for nucleic acid
      detection, using the concept of fluorescence quenching caused by the
      intramolecular excitonic interaction of fluorescence dyes. We synthesized a
      doubly thiazole orange-labeled nucleotide showing high fluorescence intensity for
      a hybrid with the target nucleic acid and effective quenching for the single
      stranded state. This exciton-controlled fluorescent probe was applied to living
      HeLa cells using microinjection to visualize intracellular mRNA localization.
      Immediately after injection of the probe into the cell, fluorescence was observed
      from the probe hybridizing with the target RNA. This fluorescence rapidly
      decreased upon addition of a competitor DNA. Multicoloring of this probe resulted
      in the simple simultaneous detection of plural target nucleic acid sequences.
      This probe realized a large, rapid, reversible change in fluorescence intensity
      in sensitive response to the amount of target nucleic acid, and facilitated
      spatiotemporal monitoring of the behavior of intracellular RNA.

PMID- 19749255
TI  - Multiple activities of c-di-GMP in Pseudomonas aeruginosa.
AB  - Survival strategies of many bacterial pathogens, including Pseudomonas
      aeruginosa, are linked to their ability to form surface associated communities
      called biofilms. The biofilm life style allows these organisms to persist in
      various tissues, avoid clearance by innate host defences and significantly
      enhanced their resistance to antibiotics. Formation of various biofilm
      components, including the synthesis of the extracellular polysaccharide matrix,
      is controlled at the transcriptional and translational levels and also by a small
      molecule second messenger bis-(3',5')-cyclic-di-guanidine monophosphate (c-di
      GMP). The synthesis of c-di-GMP from GTP and its degradation is controlled by
      diguanylate cyclases (DGCs) and phosphodiesterases (PDEs), encoded by over thirty
      genes in the P. aeruginosa genome. We have shown that an increase in the
      intracellular c-di-GMP levels favors biofilm formation due to its role as a
      cofactor for the synthesis of several types of extracellular polysaccharides,
      including PEL and alginate, the two key virulence factors of P. aeruginosa during
      infection of patients with cystic fibrosis. During biosynthesis of PEL and
      alginate, c-di-GMP binds to specific receptors, PelD and Alg44, respectively. We
      have also recently demonstrated that DGCs have a relaxed specificity and can
      cyclize other nucleotides besides GTP. These atypical cyclic dinucleotides bind c
      di-GMP receptors with high affinity, suggesting that intracellular regulation of
      various biological functions by this group of second messengers may be more
      complex than previously recognized.

PMID- 19749256
TI  - Development of peptide-oligonucleotide conjugates for regulation of small RNA
      function.
AB  - Recently, various microRNAs (miRNAs) and endogenous small interfering RNAs
      (siRNAs) have been identified and play important roles in gene regulatory
      networks. However it is a little known about their biological functions. These
      small RNAs exhibit their function to form a ribonucleoprotein complex, the RISC
      (RNA-induced silencing complex), which modulates gene expression by translational
      repression. In this study, we developed a novel peptide antagonist to inhibit the
      RISC function. The peptide was conjugated to 2'-O-methyl oligoribonucleotides,
      which have a complementary sequence to the guide strand of siRNA, and regulatory
      effects of the peptide on RISC activity were examined. It was revealed that the
      peptide drastically enhanced inhibitory effects of the oligonucleotide on RISC
      activity. Here we demonstrate our peptide-oligonucleotide conjugate that can
      provide a powerful and specific way to regulate the small RNA function.

PMID- 19749257
TI  - Studies on the effects of arginine residues introduced to peptide ribonucleic
      acids (PRNA) on the complex stability with RNA.
AB  - In this study, a series of novel alpha-Peptide ribonucleic acid (alpha-PRNA)
      oligomers, possessing alternative alpha-PRNA/arginine or serine sequences, were
      newly designed, synthesized, and evaluated as the third-generation PRNA. As
      expected, these alpha-PRNAs formed highly stable sequence-specific complexes with
      the complementary RNAs, for which both the conventional hydrogen-bonding
      interactions between the complementary nucleobase pairs and the electrostatic
      interactions between the arginine's guanidinium cation and the RNA's phosphate
      anion on the backbone are jointly responsible. Moreover, in the cases of alpha
      PRNA and single point mismatched DNA mixing systems, appreciable T(m) could not
      be observed, thus alpha-PRNAs containing Arg were expected to have high
      nucleobase sequence discrimination abilities. It was demonstrated that the
      recognition behavior of alpha-PRNA with Arg/Ser backbone with complementary RNA
      can be controlled externally through the orientation change of pyrimidine
      nucleobase induced by borate ester formation of the ribose's 2',3'-cis-diol.

PMID- 19749258
TI  - Polyethylenimine derived nanoparticles for efficient gene delivery.
AB  - Introduction of therapeutic genes into the cells of an organism in a safe and
      efficient way has become a challenging task in non-viral mediated gene therapy.
      Here, branched polyethylenimine (bPEI, 25 kDa) was converted into nanoparticles
      through electrostatic interactions with anionic polysaccharides (e.g. alginic
      acid, Al and hyaluronic acid, HA). A small library of PEI-Al and PEI-HA
      nanoparticles was synthesized by varying the amounts of anionic polysaccharides
      and evaluated in terms of their size, surface charge, cytotoxicity, transfection
      efficiency, etc. Both the series of nanoparticles exhibited higher cell viability
      and transfection efficiency as compared to native PEI and the standard
      transfection reagents. In vivo targeting efficacy of PEI-HA(4.6%) nanoparticles
      was examined in tumor induced mice.

PMID- 19749259
TI  - DNA junction structure stabilized by molecular crowding conditions.
AB  - We examined the effects of molecular crowding conditions on the structures and
      thermodynamics of three-way junctions (TWJs) of DNA. To explore the crowding
      effects on the junction point, we further evaluated the number of water molecules
      associated with the whole TWJ as well as the individual arms. It was found that
      the number of water molecules taken up by the whole TWJ was significantly smaller
      than the sum of the individual arms. These results clearly show the dehydration
      from the junction point of the TWJ structure. Therefore, molecular crowding
      should be favourable for the junction point of TWJ structure and unfavourable for
      the duplex structure. From these results, it can be concluded that a cell
      mimicking molecular crowding condition in which the activity of water decreases
      and hydration becomes less favourable, might facilitate the formation of junction
      structures in comparison with duplexes.

PMID- 19749260
TI  - Cationic comb-type copolymer as a nucleic acid chaperone for DNA quadruplex.
AB  - The intermolecular DNA quadruplex is attractive materials for design of
      nanomolecular constructs and machines. This folding kinetics is, however, slow,
      hampering its application to these materials. We have reported that the cationic
      comb-type copolymer accelerated duplex and triplex formation. In this study, the
      effect of the copolymer on the intermolecular quadruplex folding was
      investigated. The copolymer was found to accelerate the association of
      intermolecular quadruplex by three-orders. Furthermore, the copolymer induced the
      strand exchange reaction between intermolecular quadruplex and its single
      stranded counterparts. We suggested that the copolymer acts as a nucleic acid
      chaperone for the intermolecular quadruplex.

PMID- 19749261
TI  - Molecular basis of human telomere DNA/RNA structure and its potential
      application.
AB  - Telomeric repeat-containing RNA is a non-coding RNA molecule newly found in
      mammalian cells. However, structure and function of the telomeric RNA in
      chromosome ends have not yet been elucidated. Using a combination of NMR, CD and
      MALDI-TOFMS experiments, we have demonstrated that human telomere RNA can form a
      parallel G-quadruplex structure. Furthermore, we successfully found for the first
      time that human telomere DNA and RNA sequence can form a DNA-RNA hybrid type G
      quadruplex structure based on click chemistry approach. Telomerase or its
      telomere DNA substrate is also known to present a specific target in discovering
      anticancer agents. Recently, we developed a structure-based approach to sequence
      specific cleaving of human telomeric DNA by G-quadruplex formation. These results
      not only provide valuable information to allow understanding of the roles of
      human telomeric RNA in telomere biology, but also serve as a start step for
      developing new anti-cancer reagent.

PMID- 19749262
TI  - Synthetic nanocircular RNA for controlling of gene expression.
AB  - We designed and synthesized dumbbell-shaped nanocircular RNAs for RNA
      interference applications, which consist of a stem and two loops(1). RNA
      dumbbells are specifically recognized and cleaved by the human Dicer enzyme, and
      are thus transformed into double-stranded RNA in cells, although this RNA is
      resistant to degradation in serum. The structure was optimized to maximize its
      RNAi activity. The most potent activity was achieved when the stem length was 23
      base pairs. The RNAi activity is prolonged by the shape of the molecule, an
      endless structure, compared with that of normal siRNA.

PMID- 19749263
TI  - Site-specific modification of RNA by functionality-transfer ODN probes.
AB  - Efficient methods for the modification of RNA molecules have been expected as
      innovative biological tools and therapeutic methods. In this study, the
      development of a general method for site-specific RNA modification by the
      functionality-transfer ODN probes has been investigated. Site-specific and
      cytosine-selective RNA modifications were achieved by the functionality-transfer
      reaction. It was shown that the base and site-selectivity were due to the close
      proximity of the reactants in the DNA-RNA duplexes.

PMID- 19749264
TI  - Molecular design of sequence specific DNA alkylating agents.
AB  - Sequence-specific DNA alkylating agents have great interest for novel approach to
      cancer chemotherapy. We designed the conjugates between pyrrole (Py)-imidazole
      (Im) polyamides and DNA alkylating chlorambucil moiety possessing at different
      positions. The sequence-specific DNA alkylation by conjugates was investigated by
      using high-resolution denaturing polyacrylamide gel electrophoresis (PAGE). The
      results showed that polyamide chlorambucil conjugates alkylate DNA at flanking
      adenines in recognition sequences of Py-Im polyamides, however, the reactivities
      and alkylation sites were influenced by the positions of conjugation. In
      addition, we synthesized conjugate between Py-Im polyamide and another alkylating
      agent, 1-(chloromethyl)-5-hydroxy-1,2-dihydro-3H-benz[e]indole (seco-CBI). DNA
      alkylation reactivies by both alkylating polyamides were almost comparable. In
      contrast, cytotoxicities against cell lines differed greatly. These comparative
      studies would promote development of appropriate sequence-specific DNA alkylating
      polyamides against specific cancer cells.

PMID- 19749266
TI  - Site-specific incorporation of functional components into RNA by transcription
      using unnatural base pair systems.
AB  - The creation of an extra, unnatural base pair that functions in replication,
      transcription, and translation, would provide a new system for the expansion of
      the genetic alphabet. In transcription, an unnatural base pair system could be
      used for making new RNA molecules containing functional components of interest at
      specific positions. We have developed several unnatural base pairs that can
      function in replication and transcription. Among them, the 7-(2-thienyl)
      imidazo[4,5-b]pyridine (Ds) and 2-nitro-4-propynylpyrrole (Px) pair and the Ds
      and pyrrole-2-carbaldehyde (Pa) pair exhibit high selectivity and efficiency in
      PCR amplification and T7 transcription, respectively. We performed PCR
      amplification involving the Ds-Px pair for DNA template preparation and T7
      transcription involving the Ds-Pa pair with several modified Pa substrates for
      the incorporation of functional components, such as biotin- and fluorescein
      linked Pa nucleotides, into RNA. This Ds-Px and Ds-Pa pair system could provide a
      powerful tool for the site-specific fluorescent labeling and immobilization of
      RNA molecules, as a detection system for RNA and RNA-protein interactions.

PMID- 19749267
TI  - Restriction enzyme treatment/ligation independent cloning using caged primers for
      PCR.
AB  - We report here a new simple scheme for constructing recombinant vectors that does
      not require any restriction enzyme, ligase, or any other special enzyme
      treatment. By using caged primers in PCR, unnatural sticky-ends of any length and
      sequence are directly prepared on the product after a brief UVA irradiation.
      Target genes and vectors amplified by this light-assisted cohesive-ending (LACE)
      PCR join together in desired arrangement, tightly enough to be repaired and
      ligated in competent cells. We have successfully constructed a recombinant vector
      based on pBR322 and coding GFP gene by applying this simple and effective system.

PMID- 19749268
TI  - Kinetic studies of long-range hole transfer through DNA.
AB  - We report the kinetic studies of hole transfer through DNA based on the transient
      absorption measurements of photosensitizer naphthalimide (NI) and hole acceptor
      phenothiazine (PTZ) modified DNA.

PMID- 19749269
TI  - Effective algorithm to encrypt information based on self-assembly of DNA tiles.
AB  - We present an error-tolerance scheme to encrypt information in DNA structures
      based on a one-time-pad (OTP) cryptosystem that provides theoretically
      unbreakable security. The problem of the DNA-based OTP encryption is the loss of
      synchronization between the message and the encryption key due to the DNA
      property of accepting mismatched base pairs. We propose a new implementation idea
      of encrypting algorithm with the fourfold fault tolerance against mismatches than
      the ordinary DNA XOR operation. Although there are several problems to be solved
      toward the practical use at this moment, it is expected that the molecular
      computation using DNA tiles will enlarge the application possibility of the OTP
      cryptosystem.

PMID- 19749270
TI  - Three-dimensional DNA nanostructures constructed by folding of multiple
      rectangles.
AB  - The novel multi-arm DNA structures were designed using 2D-DNA Origami method, and
      these structures were folded into 3D hollow prism structures by introduction of
      connection strands into the arms. The opening of the prism structures were
      examined by a high-speed AFM, which showed the dissociation events of the
      connecting arms in the 3D-structures.

PMID- 19749271
TI  - Defining the syntax for self-assembling RNA tertiary architectures.
AB  - Stable RNAs are modular and hierarchical three-dimensional (3D) architectures
      taking advantage of recurrent structural motifs to form extensive non-covalent
      tertiary interactions (1, 2). Using comparative sequence and structural analysis
      of known X-ray structures of RNAs, folding and assembly principles of RNA can
      presently be gathered to generate the syntax of a proto-language for rational
      design and prediction of RNA 3D shapes. RNA architectonics refers to the
      deciphering of this proto-language and to its use to build new functional RNA
      shapes with self-assembly properties (3-5). This approach can therefore
      contribute to the prediction and rational design of RNA tertiary structures for
      potential applications in nanotechnology, synthetic biology and medicine.

PMID- 19749272
TI  - One-electron oxidation of DNA: mechanism and consequences.
AB  - All living organisms store the information necessary to maintain life in their
      DNA. Any process that damages DNA and causes loss or corruption of that
      information threatens the viability of the organism. One-electron oxidation is
      such a process. Loss of an electron from DNA generates a radical cation that is
      located primarily on its nucleobases. The radical cation migrates reversibly
      through duplex DNA by hopping until it is eventually trapped in an irreversible
      chemical reaction. The particular sequence of nucleobases in a DNA oligomer
      determines both the efficiency of hopping and the specific location and nature of
      the damaging chemical reaction. In its normal aqueous solutions, DNA is a
      polyanion because of the negative charge carried by its phosphate groups. Counter
      ions (typically Na(+)) to the phosphate groups play an important role in
      facilitating both the migration of the radical cation and in its eventual
      reaction with H(2)O. Irreversible reaction of a radical cation with H(2)O in
      duplex DNA occurs preferentially at the most reactive site. In normal DNA that is
      comprised of the four common DNA nucleobases, reaction occurs most commonly at a
      guanine and results in its conversion primarily to 8-oxo-7,8-dihydroguanine (8
      OxoG). Both electronic and steric effects control the outcome of this process. If
      the DNA oligomer does not contain a suitable guanine, then reaction of the
      radical cation occurs at the thymine of a TT step primarily by a tandem process.
      The general outcomes revealed in the one-electron oxidation of DNA oligomers in
      solution appear to be generally valid also for more complex DNA structures and
      for the cellular DNA of living organisms.

PMID- 19749273
TI  - Structure and real-time monitoring of the enzymatic reaction of APOBEC3G which is
      involved in anti-HIV activity.
AB  - Human apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G
      (APOBEC3G) is known to play a role in intrinsic cellular immunity against human
      immunodeficiency virus type 1 (HIV-1). The antiretroviral activity of APOBEC3G is
      associated with hypermutation of viral DNA through cytidine deamination. APOBEC3G
      contains two cytidine deaminase domains that are characterized by a highly
      conserved zinc-coordinating motif. It is known that only the C-terminal domain of
      APOBEC3G (c-APOBEC3G) is involved in the catalytic activity. Here, we present the
      solution structure and the interaction with single-stranded DNA of c-APOBEC3G.
      Furthermore, we have succeeded for the first time in monitoring the deamination
      reaction of c-APOBEC3G in real-time using NMR signals. The monitoring has
      demonstrated that the deamination reaction occurs in a strict 3'-->5'

PMID- 19749274
TI  - NMR studies of DNA recognition mechanism of HMGB1 protein.
AB  - A 2'-deoxyuridylate dimer cyclized via cross-linkage by an ethylene (U(et)(p)U)
      or a propylene (U(pr)(p)U) linker at the 5-position was incorporated into DNA
      oligomers. Fluorescence resonance energy transfer (FRET) experiments showed that
      they bent at approximately 90 degrees . We investigated binding abilities of
      U(et)(p)U and U(pr)(p)U DNA oligomers to HMGB1 A-box protein, which specifically
      binds to bent DNA, using nuclear magnetic resonance (NMR) spectroscopy. Both DNA
      oligomers bind to HMGB1 A-box protein, however, the U(et)(p)U DNA oligomer has
      higher affinity than the U(pr)(p)U DNA oligomer. In order to explain this
      difference, we studied the solution structures of the U(et)(p)U and U(pr)(p)U DNA
      oligomers using NMR. Most (1)H signals except for 4', 5' and 5'' were assigned.
      Cross-peak patterns of (1)H-(1)H NOESY spectra indicate that both oligomers have
      right-handed B-form like structures and the cyclization in 2'-deoxyuridylates
      does not break Watson-Crick base pairs. Chemical shift differences between these
      two DNA oligomers suggest the presence of the local structural differences in the
      region of 2'-deoxyuridylate dimer and its 3' side between the U(et)(p)U and
      U(pr)(p)U DNA oligomers.

PMID- 19749275
TI  - Analysis of the spacial requirements for RNA-protein interactions within the N
      antitermination complex of bacteriophage lambda.
AB  - In bacteriophage lambda, formation of a transcriptional antitermination complex
      consisting of the lambda N protein, nut RNA transcript (boxA-boxB), host factors,
      and RNA polymerase is mediated by the interaction of the boxB RNA with the RNA
      binding domain of N. In order to understand the spacial requirements of this
      boxB/N interaction within the complex, the effects of changes in the length of
      the nut site linker, the boxB stem, and the peptide spacer connecting the RNA
      binding domain and activation domain of N were examined using a bacterial
      reporter system. As a result, we found that the requirements for the boxB stem
      length and N peptide linker length were optimized and strict. In contrast, when
      the boxB/N interaction was replaced by heterologous RNA/peptide interactions, the
      strict requirement for the length of the peptide linker and the RNA stem was
      relaxed, presumably due to the absence of the interaction between boxB/N and the
      host factor NusA in the wild-type complex. It was also shown that the decrease in
      activity upon stem lengthening could be partially suppressed by simultaneous
      lengthening of the RNA spacer, suggesting that a further understanding of the
      organization of the antitermination complex may provide insights into the
      engineering of functional ribonucleoprotein complexes.

PMID- 19749276
TI  - Monitoring biological interactions using perforated evanescent-field-coupled
      waveguide-mode nanobiosensors.
AB  - Evanescent-field-coupled (EFC) waveguide-mode sensors recently been shown to be
      suitable for detecting various biomolecules. In the present studies, we
      demonstrated that both nucleic acids hybridization and nucleic acids-protein
      interactions can be analyzed using perforated evanescent-field-coupled waveguide
      mode nanobio-sensors.

PMID- 19749277
TI  - 9-(2-C-Cyano-2-deoxy-beta-D-arabino-pentofuranosyl)guanine, a potential antitumor
      agent against B-lymphoma infected with Kaposi's sarcoma-associated herpesvirus.
AB  - Several 9-(2-C-cyano-2-deoxy-l-beta-D-arabino-pentofuranosyl)purine derivatives
      were tested against Kaposi's sarcoma-associated herpesvirus (KSHV)-infected
      primary effusion lymphoma (PEL) cells. The guanine derivative (2, CNDAG) as well
      as the 2-amino-6-substituted-purine derivatives 3, 4 and 5 inhibited KSHV
      positive cell growth but showed no cytotoxicity against KSHV-negative cells at
      >15 muM concentrations. Therefore, it was found that compounds 2, 3, 4 and 5
      showed selective cytotoxicity against PEL cells infected with KSHV.

PMID- 19749278
TI  - Synthesis and anti-HIV activity of 4'-C-ethynyl-2'-deoxy-4'-thio-nucleosides.
AB  - Synthesis of 4'-C-ethynyl-2'-deoxy-4'-thionucleosides was carried out based on
      electrophilic glycosidation using 4-C-ethynyl-4-thiofuranoid glycal. The glycal
      15 was prepared as follows: oxidative cleavage of 6 with Pb(OAc)(4) forming the
      aldehyde 7, aldol reaction of 7 and subsequent silylation to furnish 8,
      conversion of the formyl group of 8 into an ethynyl group, and finally beta
      elimination of the resulting 14 with t-BuLi. The glycosyl donor 16 was prepared
      by silyl-protection of 15. Electrophilic glycosidation was performed between
      silylated N(4)-acetylcytosine and 16 in the presence of N-iodosuccinimide.
      Radical-mediated removal of the introduced iodine atom followed by deprotection
      gave 4'-C-ethynyl-2'-deoxy-4'-thiocytidine (18).

PMID- 19749279
TI  - Synthesis of 4'-substituted cordycepins via benzenesulfenylation at the 4'
      position as a key step.
AB  - With an aim to synthesize 4'-substituted cordycepins, the 4'-phenylthio precursor
      4 was prepared from adenosine through an electrophilic addition to the 3',4'
      unsaturated derivative 2 by using NIS/PhSH system. Nucleophilic substitution of 4
      with a series of alcohols in the presence of NBS gave the respective 4'-alpha
      alkoxy cordycepins 6 as the major stereoisomer. Use of DAST, in stead of alcohol
      in this reaction, gave the 4'-fluoro analogue 7. The 4'-sulfone derivative 8
      obtained by m-CPBA oxidation of 4 was employed for the reaction with
      organoaluminum reagents. These reactions furnished various types of the 4'-carbon
      substituted cordycepins 9.

PMID- 19749280
TI  - Synthesis of 5'-fluoro-2'-beta-methylneplanocin analogues.
AB  - Synthesis of 5'-fluoro-2'-beta-methylneplanocin analogues (5) was carried out.
      The cyclopentenone 16 was prepared from methyl mannopyranoside by using ring
      closing metathesis, stereoselective introduction of methyl group, and seleno
      cyclization as representative steps. Introduction of a fluorine atom was
      conducted by electrophilic fluorination. Antiviral activity of 5 will also be
      presented.

PMID- 19749281
TI  - Synthesis and anti-HCV activity of 2',5'-deoxy-5'-phenacyladenosine analogs.
AB  - Several nucleoside analogs containing a methylene group instead of a 5'-O atom
      were synthesized to study the effect of the 5'-modification of nucleoside analogs
      on their anti-HCV activity. Among the analogs, a 5'-phenacyl analog exhibited
      good anti-HCV activity with an EC(50) of 15.1 muM. This compound is hypothesized
      to function via a novel type of mechanism that does not involve the conventional
      5'-O-triphosphorylation process.

PMID- 19749282
TI  - Synthesis of deuterated benzyladenine and its application as a surrogate.
AB  - Palladium on carbon-ethylenediamine complex [Pd/C(en)] catalyzed deuteration of
      N(6)-benzyladenine-d(5), which is a plant growth regulator, to introduce 5
      deuterium atoms, while use of Pd/C as a catalyst led to a complete removal of
      N(6)-benzyl group. The corresponding deuterated N(6)-benzyladenine was
      successfully used as a surrogate compound for the quantitative analysis of
      residual benzyladenine in crops using LC/MS/MS.

PMID- 19749283
TI  - Synthesis and properties of a novel artificial nucleoside that acts as a redox
      switch.
AB  - Oligonucleotide that can reversibly alter the duplex-forming ability in response
      to an external factor has potential to be applied to various genome technologies,
      e.g. antisense and gene diagnosis technology. A novel bridged nucleoside which is
      capable of sensing an oxidant and reductant was designed and synthesized. The
      nucleoside formed a disulfide bridge between C2' and C4' positions, which would
      enhance its duplex-forming ability under oxidative conditions. Contrastingly, the
      disulfide bridge was cleaved under reductive conditions; it could cause decrease
      of duplex-forming ability.

PMID- 19749284
TI  - The use of conformationally rigid nucleoside probes to study the role of sugar
      pucker and nucleobase orientation in the thrombin binding aptamer.
AB  - Thrombin binding aptamers (TBAs) incorporating North-/South-deoxyguanosines built
      on the rigid bicyclo[3.1.0]hexane template were synthesized. Individual 2'
      deoxyguanosines at positions dG14 and dG15 of the aptamer were replaced by these
      analogues where the North/anti and South/syn conformational states were confined.
      The substitution at position 14 with a locked South/syn-dG nucleoside produced an
      aptamer with the same stability and global structure as the innate, unmodified
      one. Replacing position 15 with the same South/syndG nucleoside induced a strong
      destabilization of the aptamer, while the antipodal North/anti-dG nucleoside was
      less destabilizing. Remarkably, the insertion of a North/anti-dG nucleoside at
      position 14, where both pseudosugar conformation and glycosyl torsion angle are
      opposite with respect to the native structure, led to the complete disruption of
      the G-tetraplex structure as detected by NMR and confirmed by extensive molecular
      dynamics simulations.

PMID- 19749285
TI  - Chemical synthesis of nucleoside H-boranophosphonates and their application as
      precursors of P-modified nucleotide analogues.
AB  - Nucleoside H-boranophosphonates were synthesized via the condensation reactions
      of appropriately protected nucleosides with monopyridinium H-boranophosphonate
      and subsequent deprotection under basic conditions. 3',5'-O-Protected
      dinucleoside H-boranophosphonates were also synthesized via the condensation of
      the corresponding 5'-O-protected nucleoside 3'-H-boranophosphonates with 3'-O
      protected nucleosides. A study on the chemical properties of the resultant
      dinucleoside phosphate analogues revealed that the P-H group could be further
      modified under anhydrous basic conditions.

PMID- 19749286
TI  - Stabilization of A-type nucleic acid duplexes by novel oligodiaminosaccharides.
AB  - Novel oligodiaminosaccharides, alpha-(1-->4)-linked-2,6-diamino-2,6-dideoxy-D
      glucopyranose oligomers, were designed and synthesized to bind to A-type nucleic
      acid duplexes, such as RNA duplexes. Using properly designed glycosyl donors and
      glycosyl acceptors, an alpha-selective glycosylation was achieved. A chain
      elongation cycle was established and the oligodiaminosaccharides bearing the
      alpha-glycoside bonds (1-4mer) were synthesised. Analyses of their interactions
      with oligonucleotide duplexes were performed by using CD spectrometry and UV
      melting experiments. These experiments revealed that the 3mer and 4mer were found
      to remarkably stabilize RNA-RNA and RNA-DNA duplexes with small structural
      changes.

PMID- 19749287
TI  - Synthesis and hybridization properties of oligonucleotides having 4-N-(pyrrol-2
      ylcarbonyl)deoxycytidine.
AB  - A new 4-N-acylated deoxycytidine derivative, 4-N-(1H-pyrrol-2
      ylcarbonyl)deoxycytidine, was synthesized and found to be stable under rather
      basic conditions. Oligodeoxynucleotides (ODNs) incorporating this modified
      deoxynucleoside at various positions were successfully synthesized by using a
      pivaloyloxymethyl (POM) group for protection of the pyrrole residue. The POM
      group was removed by treatment with 1.5 M NaOMe/MeOH. ODNs containing modified
      deoxycytidines exhibited hybridization properties superior to those of the
      unmodified ODNs. We found the acylation of the cytosine base with an aromatic
      acyl-type substituent led to significant increase of the thermo stability of DNA
      duplexes. This is the first noteworthy observation in this kind of modification.
      The synthesis and hybridization properties of 4-N-(1H-pyrrol-2
      ylcarbonyl)deoxycytidine derivatives will be also reported.

PMID- 19749288
TI  - Synthesis and properties of new RNA molecules incorporating 2'-O-aryluridine
      derivatives.
AB  - A variety of 2'-O-arylnucleosides with functional groups were synthesized by the
      microwave-assisted reaction of 2,2'-anhydrouridine with phenol derivatives. The
      2'-O-arylnucleosides thus obtained were incorporated into 2'-O-Me RNA or DNA
      oligomers and their hybridization properties were studied by T(m) measurements.

PMID- 19749289
TI  - Synthesis of modified double stranded RNAs containing duplex regions between
      amide-linked RNA and RNA at both ends and enhanced nuclease resistance.
AB  - Synthetic short-interfering RNA (siRNA) has been a powerful tool to control gene
      expression. Chemical modification of the 3'-overhang regions of siRNA with amide
      linked RNAs improved the exonuclease resistance and was compatible with RNAi
      function in cultured cells. To improve endonuclease resistance of the siRNA
      having amide-linked RNA modification at the 3'-terminal regions, we designed and
      synthesized new modified double stranded RNAs (dsRNAs) the 3'-terminal regions of
      which were modified with amide-linked RNA moieties and formed duplex structures
      with the complementary unmodified RNA moieties. The modified dsRNAs showed
      remarkable increase of stability in cell culture medium containing 10% serum in
      comparison with the modified siRNAs having 3'-overhang regions of amide-linked
      RNAs. The result suggests that the resistance of siRNA against endonuclease as
      well as 3'-exonuclease in serum can be enhanced by the introduction of the
      structures of amide-linked RNA:unmodified RNA duplexes at both ends of siRNA.

PMID- 19749290
TI  - 5'-Lipophilic conjugates of oligonucleotides as components of cell delivery
      systems.
AB  - The approach to the synthesis of 5'-lipophilic conjugates of functional nucleic
      acids based on a combination of H-phosphonate and phosphoramidite methods is
      presented.

PMID- 19749291
TI  - Introduction of 8-methyladenosine into 2', 5'-oligoadenylate (2-5A) 2'-terminus
      induces dramatic shift in binding site of RNase L.
AB  - The 2',5'-oligoadenylate (2-5A) system is an interferon (IFN)-regulated RNA decay
      pathway that provides innate immunity against viral infections. The biological
      action of the 2-5A system is mediated by RNase L, an endoribonuclease that
      becomes enzymatically active after binding to 2-5A. It has been reported that the
      5'-phosphoryl group of 2-5A is required for RNase L activation. However, we have
      found that 5'-O-dephosphorylated 2-5A tetramer analogs with 8-methyladenosine at
      the 2'-terminus were more effective as an activator of RNase L than the parent 2
      5A (p5'A2'p5'A2'p5'A2'p5'A2'). Introduction of 8-methyladenosine is thought to
      induce a dramatic shift in the binding site of RNase L.

PMID- 19749292
TI  - Unnatural imidazopyridopyrimidine:naphthyridine base pairs: selective
      incorporation and extension reaction by DNA polymerases.
AB  - We describe herein the results of (i) enzymatic recognition for
      imidazopyridopyrimidine (Im):naphthyridine (Na) base pairs and (ii) further
      primer extension reactions after the Im:Na base pairs by DNA polymerases. Among
      the base pairs examined, ImN(O):NaO(N) base pair was rather selectively
      recognized by Klenow fragment exo(-) [F(exo(-))]as complementary base. However,
      this DNA polymerase did not catalyze primer extension reactions after the
      ImN(O):NaO(N) base pair. Therefore, we carried out a screening of DNA polymerases
      to promote the primer extension reaction as well as to improve the selectivity of
      base pair recognition. As a result, a family B DNA polymerase, especially Deep
      Vent (exo(-)), seemed most promising for this purpose.

PMID- 19749293
TI  - Evaluation of base recognition abilities of 2'-deoxynucleoside N-oxide
      derivatives by polymerase reactions.
AB  - The main products obtained by oxidation of cytosine and adenine bases with
      hydrogen peroxide are cytosine and adenine N-oxide derivatives. There is a
      possibility that these N-oxide derivatives are mutagenic in genomic DNA like 8
      oxoguanine or thymine glycol. Although the chemical synthesis and properties of
      2'-deoxynucleoside N-oxide derivatives have been well established, little has
      been reported about the chemical and biochemical behavior of
      oligodeoxynucleotides (ODNs) containing these modified 2'-deoxynucleoside. In
      this study, we examined their base recognition ability by DNA polymerase
      reactions. It was found that these modified derivatives were incorporated into
      the 3'-terminal site of an ODN by DNA polymerase selecting accurately the
      complementary G or T base on a template ODN. In the incorporation reaction using
      template ODNs containing 2'-deoxynucleoside N-oxide bases, their N-oxide bases
      were selectively recognized by the complementary 5'-triphosphate (dGTP or dTTP).

PMID- 19749294
TI  - Preparation of eukaryotic mRNA having differently methylated adenosine at the 5'
      terminus and the effect of the methyl group in translation.
AB  - Cap analogues having differently methylated adenosine at 2' and N6 position,
      m(7)G(5')pppApG which is existed in plant mRNA (plant type), m(7)G(5')pppAmpG
      (animal type), m(7)G(5')pppm(6)AmpG (mammalian type) and m(7)G(5')pppm(6)ApG
      (unnnatural type), were synthesized. In order to clarify the function of these
      methyl groups, luciferase mRNAs having differently methylated adenosine at the 5'
      terminus, were successfully prepared by in vitro transcription using the
      synthesized cap anologues. As the preliminary results of in vitro translation
      with rabbit reticulocyte lysate and luciferase assay, luciferase mRNA having the
      mammalian type of cap structure, m(7)G(5')pppm(6)AmpG, was most efficiently
      translated. In the case of m(7)G(5')pppApG (plant type) efficiency of translation
      was lowest.

PMID- 19749295
TI  - Synthesis and characterization of deoxyuridine triphosphates labeled with pyrene.
AB  - Deoxyuridine triphosphate derivatives modified with pyrene was synthesized to
      functionalize DNA with fluorescent molecules based on the template DNA sequence.
      Incorporation of pyrene-labeled deoxyuridine triphosphates into DNA by DNA
      polymerase was investigated by using reverse-phase HPLC and polyacrylamide gel
      electrophoresis. The fluorescent properties of functionalized DNA were
      characterized by the steady-state fluorescence measurements.

PMID- 19749296
TI  - Duplex formation of multiple pyrene-modified RNAs.
AB  - We synthesized multiple pyrene-modified RNA sequences having two kinds of
      consecutive sequences, U(Py)U(Py) and A(Py)A(Py), and investigated their duplex
      formations and the pyrene associations.

PMID- 19749297
TI  - Synthesis and properties of new fluorescent nucleosides and oligodeoxynucleotides
      derived from 5-formyl-2'-deoxyuridine.
AB  - 5-Formyl-2'-deoxyuridine (fdUrd) is a product of the oxidation of thymidine and
      is known to induce mutation (A:T to G:C) in DNA. Therefore, a selective detection
      method for fdUrd is needed, but convenient methods have not been developed. We
      planned to develop a novel selective method to detect fdUrd in damaged DNA based
      on a specific fluorogenic derivatization of fdUrd using 2-aminothiophenol
      derivatives (ATs) as fluorogenic reagents. To achieve this goal, we first
      investigated the synthesis and fluorescence properties of some 5-(benzothiazol-2
      yl)-2'-deoxyuridine derivatives (btdUrds). We also report the reaction between
      oligodeoxynucleotides (ODNs) containing fdUrd and ATs.

PMID- 19749298
TI  - Fluorescent properties of acridonyl group in DNA duplex.
AB  - We designed and synthesized a nucleoside derivative in which the nucleobase is
      replaced with acridone. The nucleoside derivative was incorporated into an
      oligodeoxyribonucleotide (ODN), and its influence on the stability of ODN hybrids
      and its fluorescent properties in a DNA duplex were measured by thermodynamic
      analysis and fluorescent spectroscopy. These results showed that the acridonyl
      group could distinguish the type of nucleobase paired from fluorescent intensity,
      although the hybrid stability did not depend significantly on the types of
      nucleobases paired.

PMID- 19749299
TI  - Optimization of the sequence of twisted intercalating nucleic acids (TINA)
      forming triple helix with the polypurine tract of the proviral HIV DNA.
AB  - Twisted intercalating nucleic acids form stable triplexes with polypurine tracts
      of double-stranded DNA. Their affinity depends on their length, primary structure
      and base contents, parallel or antiparallel orientation of oligonucleotides
      respectively to DNA, number of TINA residues and their relative positions. Basing
      on parallel CT, GT and antiparallel GT triplex-forming 16-mer oligonucleotides
      targeted to polypurine tract of HIV proviral DNA, we synthesized eleven different
      oligonucleotides with 2-4 TINA insertions in different positions. Studies of
      their interaction with target duplex by gel shift, fluorescence spectroscopy,
      circular dichroism and thermal denaturation demonstrated that antiparallel GT
      oligonucleotides form more stable triplexes than parallel TC or TG ones. Two best
      candidates were selected for the further studies. The first one (5'
      AGGGxGGGTTTxTGTTTT-3', Kd = 219 nM) contains only two TINA insertions and does
      not aggregate in non-denaturing conditions, in contrast to majority of other
      oligonucleotides.

PMID- 19749300
TI  - Design of extremely facile 3'- and 5'- ends free molecular beacons using C8
      alkylamino substituted 2'-deoxyguanosine.
AB  - A novel fluorescent oligonucleotide probe containing pyrene-labeled C8 alkylamino
      substituted 2'-deoxyguanosine and a practically useful 3'- and 5'- ends-free self
      quenched molecular beacons (MB) were designed. A unique MB detectable by pyrene
      excimer fluorescence was also demonstrated.

PMID- 19749301
TI  - Multipyrene tandem probes for detection of C677T polymorphism in MTHFR gene.
AB  - We designed tandems of oligo(2'-O-methylribonucleotides) conjugates containing
      two bispyrene (5'-bisPyr and 3'-bisPyr) groups on their junction for detection of
      C677T polymorphism in the methylenetetrahydrofolate reductase gene (MHTFR). The
      potential of SNP detection with multipyrene tandems of oligo(2'-O
      methylribonucleotides) was demonstrated.

PMID- 19749302
TI  - Synthesis and hybridization of oligonucleotides attached to a redox reporter via
      ethenyl linker at 5-position of pyrimidine base.
AB  - We describe a new ferrocene-based redox-reporter that electronically couples to
      the DNA Pi-electron system.

PMID- 19749303
TI  - Immobilization of a naphthalene diimide-DNA complex on the gold through
      dithiolane moieties.
AB  - Naphthalene diimide 1 having two dithiolane moieties at its substituted termini
      was newly synthesized to immobilize double stranded DNA through dithiolane
      moieties of 1. Double stranded DNA could be immobilized on the gold surface of a
      quartz crystal microbalance (QCM) chip after binding 1. Once immobilized, the
      complex will serve as a hybridization marker based on its frequency decrease. QCM
      experiments showed that a DNA duplex with a 24-meric single stranded region also
      could be immobilized on the gold surface of a QCM chip and subsequent frequency
      decrease was observed after hybridization with a 24-meric complementary DNA, but
      not with non-complementary DNA, indicating specific hybridization. This result
      reveals that 1 provides a new immobilization method for intact DNA on gold and
      that the immobilized DNA can hybridize with target DNA.

PMID- 19749304
TI  - Strategies for preparation of oligonucleotide biochips and their applications.
AB  - In the last few years, DNA-microarray technology has emerged as a powerful tool
      for gene discovery, detection of mutations, and mapping. Here, we have developed
      a simple and efficient single-step method for immobilization of phosphoryl-,
      mercaptoalkyl-, thiophosphoryl- and aminooxyalkylated oligonucleotides onto an
      epoxylated glass surface. It resulted in higher immobilization and hybridization
      efficiency in comparison to those obtained with the standard method. The probes
      immobilized were found to be stable over a range of temperature and pH,
      suggesting that the chemistry could be used in integrated PCR/microarray devices.
      Also the immobilized spots were found to be of superior quality in terms of spot
      morphology, homogeneity and signal reproducibility. The constructed microarrays
      were successfully used for the discrimination of nucleotide mismatches and
      detection of bacterial diseases.

PMID- 19749305
TI  - Evaluation of mobility of 2-N-tert-butylaminoxyladenosine incorporated into
      oligodeoxynucleotides.
AB  - We synthesized oligodeoxynucleotide (ODN, 3) containing 2-N-tert
      butylaminoxyladenosine (1) and studied EPR spectra of 3 and its duplexes. The
      h(+)/h(0) values in the EPR spectra of duplexes between 3 and 5-8 well correlated
      with Tm values. We also synthesized ODN 4 containing 2, which has a cyclic
      aminoxyl via a linker, to compare with ODN 3. The h(+)/h(0) values in the EPR
      spectra of duplexes between 4 and 5-8 did not correlate with Tm values. These
      results indicate that 1 has a potential to monitor of motion of the nucleobase.

PMID- 19749306
TI  - Real-time monitoring of mRNAs with fluorescence-modified RNA probes in living
      cells.
AB  - In our previous study, we reported that bispyrene-modified RNA probes (OMUpy2)
      were useful for RNA detection in homogeneous physiological media(1-2). The aim of
      this study is to establish in situ monitoring system to detect mRNAs in living
      cells by OMUpy2. We chose c-fos mRNA as a target RNA which is known as one of the
      immediate-early genes. The real-time moni- toring of mRNAs was carried out in
      living C4II cells. After transfection of OMUpy2 into the cells which had been
      incubated with serum-free medium, cells were stimulated by media with serum and
      the resulting expression of mRNA was monitored by a fluorescence microscope. In
      the case of OMUpy2-CF3S, which was complementary to c-fos mRNA, fluorescence
      emission around 480 nm was observed obviously. These results suggest that mRNA
      expressed by the serum stimulation was successfully visualized in a real-time
      manner.

PMID- 19749307
TI  - Synthesis of exciton-controlled fluorescent probes for RNA imaging.
AB  - The excitonic interaction of thiazole orange dyes is known to suppress
      fluorescence emission. We have developed hybridization-sensitive fluorescent
      probes utilizing the excitonic interaction of two thiazole orange dyes connected
      to the probes. Here, we report nuclease-resistant hybridization-sensitive probes
      for long-term intracellular RNA imaging.

PMID- 19749308
TI  - Protein detection using oligonucleotide probes.
AB  - We developed a new nucleic acid-based fluorescence probe for protein detection.
      The method is based on the scission of an aptamer into two probes, which are then
      attached with a chemically reactive fluorogenic compound. The protein-dependent
      association of the two probes accelerates a chemical reaction and indicates the
      presence of the target protein, which is detected using a fluorescence readout.
      The arginine-rich motif peptide was targeted by this type of probe. In presence
      of the peptide, the fluorescence signal at 450 nm increased, and no significant
      increase in fluorescence was observed in the absence of the peptide. An
      oligonucleotide-based fluorescence probe was successfully applied to the
      detection of the ARM peptide in solution.

PMID- 19749309
TI  - Promotion of triplex formation by 3'-amino-2'-O,4'-C-methylene bridged nucleic
      acid modification.
AB  - We examined the effect of 3'-amino-2'-O,4'-C-methylene bridged nucleic acid (3'
      amino-2',4'-BNA) backbone modification of triplex-forming oligonucleotide (TFO)
      on the pyrimidine motif triplex formation at neutral pH, a condition where
      pyrimidine motif triplexes are unstable. The melting temperature of the
      pyrimidine motif triplex at pH 6.8 with 3'-amino-2',4'-BNA modified TFO was
      significantly higher than that observed with unmodified TFO. The 3'-amino-2',4'
      BNA modification of TFO increased the thermal stability of the pyrimidine motif
      triplex at neutral pH. The present results certainly support the idea that the 3'
      amino-2',4'-BNA modification of TFO could be a key chemical modification and may
      eventually lead to progress in therapeutic applications of the antigene strategy
      in vivo.

PMID- 19749310
TI  - Promotion of strand invasion by utilizing entropically-favored PNA.
AB  - Invasion of peptide nucleic acid (PNA) is important to target a specific site in
      double-stranded DNA. However, it needs improvement in many ways such as sequence
      versatility and invasion efficiency. It is here reported that one 10-mer strand
      of alpha-lysine substituted peptide nucleic acid (PNA) efficiently invades double
      stranded DNA (dsDNA) in the presence of single-strand binding protein (SSB) via
      Watson-Crick rule. According to the thermodynamic parameters in this study,
      highly efficient invasion was achieved by a favorable entropy change. The
      importance of preorganization of PNAs for efficient strand invasion is indicated.

PMID- 19749311
TI  - Development of new DNA triplex triads by using 5-substituted deoxycytidine.
AB  - We developed a new artificial DNA triplex triad which has the adenine nucleobase
      in the first strand. This triplex triad (A-psi-C*) is composed of adenine,
      pseudouridine and 5-sudstituted cytosine as the 1st, 2nd and 3rd strand
      nucleobases, respectively. The molecular design and synthesis of the nucleobases
      for the 2nd and 3rd strand of the triplex are also described.

PMID- 19749312
TI  - Synthesis and thermal denaturation studies of covalently linked DNA triplexes.
AB  - We report on the synthesis and thermal stability of small covalently linked DNA
      triplexes. These modified triplexes were found to contain covalently linked T-T
      pairs at the edges, and thermal denaturation studies revealed that the covalent
      linking efficiently stabilized triplex formation.

PMID- 19749313
TI  - Evaluation of the antisense effect of PEGylated oligodeoxynucleotides containing
      intelligent nucleoside analogues.
AB  - We have previously reported that the 2-amino-6-vinylpurine (AVP) in
      oligonucleotide (ODN) showed the highly selective and effective cross-linking
      reaction toward cytosine within target complementary sequences. Recently, we
      revealed that the PEGylated ODN containing AVP analogues exhibited the effective
      antisense effect in the cultured cell. However, subsequent studies showed that
      the cross-linking ability of AVP for cytosine was affected by the target RNA
      sequences. We therefore developed new intelligent nucleoside analogues connected
      AVP to sugar through the ethylene linker (et-AVP), that exhibited highly
      effective cross-linking ability to rC in the target RNA. In this paper, we
      described the synthesis of the PEGylated ODN containing cross-linking nucleoside
      analogues and properties of it about RNase H activity and antisense effect in
      cell lysate. As a result, the PEGylated ODN containing et-AVP showed the
      effective antisense effect in the non-cell system for targeting the luciferase
      mRNA by non-RNase-H mechanism.

PMID- 19749314
TI  - Design and synthesis of the novel cross-linking agent.
AB  - Previously, we have developed a highly efficient and selective cross-linking
      reaction to the cytosine base at the target site of DNA using the
      oligodeoxynucleotide (ODN) containing 2-amino-6-vinylpurine derivative (1). Based
      on these results, we have designed the novel cross-linking agents, which are
      pyrimidine derivatives having two hydrogen bond sites and vinyl group as a
      reactive moiety. In this paper, we wish to report the results to investigate on
      the synthesis of the pyrimidine derivatives having potential as novel cross
      linking agents.

PMID- 19749315
TI  - DNA cross-link generated by a novel modified DNA containing a formyl group.
AB  - We here report the synthesis of novel modified nucleic acid containing a formyl
      group and the evaluation of interstrand cross-linking between the modified DNA
      and the complementary strand. The synthesis of the formyl-containing
      oligodeoxynucleotide (ODN) was achieved by a post synthetic modification of
      corresponding ODN containing a 1,2-diol. The ODN containing the diol moiety was
      successfully synthesized by a standard phosphoramidite method, and was
      quantitatively converted to the desired formyl-containing ODN by sodium periodate
      oxidation. Hybridizaiton of the formyl ODN and the complementary ODN produced the
      interstrand cross-link between the formyl group and N(6)-exocyclic amino group of
      adenine.

PMID- 19749316
TI  - DNA ligation using photoremovable protecting groups.
AB  - Template-directed ligation of oligonucleotides by photochemical reaction has
      attracted much interest because of its biomedical and synthetic applications. In
      this study, we developed photoligaton of DNA by using a photoremovable protecting
      group and thiol-disulfide exchange reaction. A phosphoroamidite of o-nitrobenzyl
      derivatives were synthesized, and DNA modified with a nitrobenzyl-protected thiol
      group and disulfide group was synthesized by conventional phosphoroamidite
      chemistry using a DNA synthesizer. It was shown that photochemical reaction of a
      nitrobenzyl group with UV irradiation produced a free thiol group, leading to the
      DNA ligation through the thiol-disulfide exchange reaction.

PMID- 19749317
TI  - Handy and prompt DNA separation using PNA with internal disulfide bond.
AB  - PNA (peptide nucleic acid) is a DNA analogue which has a peptide backbone. PNA is
      very useful as a recognition probe because of its immensely high affinity to DNA.
      In this study, we used PNA as a DNA separation tool. Furthermore, we introduced a
      cleavable disulfide bond into main chain of PNA in order to facilitate the
      removal of PNA from PNA/DNA duplex. This disulfide bond was readily cleaved by
      various reducing agents and then the resultant two short PNA fragments could not
      form stable PNA/DNA duplex anymore. Accordingly, a desired DNA fragment was
      picked up from the DNA mixtures and readily recovered by the reductive treatment.

PMID- 19749318
TI  - Radiolytic one-electron reductive cyclization of oligodeoxynucleotides possessing
      a disulfide bond.
AB  - Radiolytic one-electron reduction of oligodeoxynucleotides (ODNs) possessing a
      disulfide bond induced strand exchange reaction in a hypoxia selective manner. In
      this study, we attempted to apply this radiolytic reaction to stem-and-loop
      structured ODNs. Hypoxic X-irradiation to an aqueous solution of stem-and-loop
      structured ODNs produced a cyclized DNA in good yield via an intrastrand ligation
      reaction.

PMID- 19749319
TI  - Development of a novel method to determine the concentration of heavy metal
      cations: application of the specific interaction between heavy metal cation and
      mismatch DNA base pair.
AB  - We have already found that Hg(II) cation specifically binds to T:T mismatch base
      pair in heteroduplex DNA, which increases the melting temperature of heteroduplex
      DNA involving T:T mismatch base pair by about 4 degrees C. We have also found
      that Ag(I) cation specifically binds to C:C mismatch base pair in heteroduplex
      DNA, which increases the melting temperature of heteroduplex DNA involving C:C
      mismatch base pair by about 4 degrees C. Using the specific interaction, we
      developed a novel sensor to determine the concentration of each of Hg(II) and
      Ag(I) cation. The sensor is composed of a dye-labelled T-rich or C-rich DNA
      oligonucleotide, F2T6W2D: 5'-Fam-T(2)CT(2)CT(2)C(4)T(2)GT(2)GT(2)-Dabcyl-3' or
      F2C6W2D: 5'-Fam-C(2)TC(2)TC(2)T(4)C(2)AC(2)AC(2)-Dabcyl-3', where 6
      carboxyfluorescein (Fam) is a fluorophore and Dabcyl is a quencher. The addition
      of Hg(II) cation decreased the intensity of Fam emission of F2T6W2D at 520 nm in
      a concentration-dependent manner. Also, the addition of Ag(I) cation decreased
      the intensity of Fam emission of F2C6W2D at 520 nm in a concentration-dependent
      manner. We conclude that, using the novel sensor developed in this study, the
      concentration of each of Hg(II) and Ag(I) cation can be determined from the
      intensity of Fam emission at 520 nm.

PMID- 19749320
TI  - Electronic structure and UV absorption spectra of metal-mediate DNA: an approach
      from theoretical chemistry.
AB  - We theoretically evaluated the stability, UV-Vis spectra and possibility of
      stacking of [S-M(II)-S] (M=Ni, Pd, Pt, S: hydroxypyridonethione) by means of the
      density functional theory (DFT). From the view of the free energy, we assessed
      formation energy of possible combinations of chalcogen atoms and metal cations.
      The results confirmed that [H-Ni(II)-H] and [S-Cu(II)-S] would form stable metal
      base pairing, on the other hand [H-Pt(II)-H] would not, which have been
      experimentally proven. Moreover, by use of time-dependent density functional
      theory (TDDFT), we observed d-pi* transition accompanied with pi-pi* transition
      in [S-M(II)-S]. These results reveal that metal-to-ligand charge transfer (MLCT)
      shifts the peak of pi-pi* transition in [S-2H(+)-S] (without metal cations).

PMID- 19749321
TI  - Acceleration of guanine oxidation under visible light irradiation by photon
      upconversion based on triplet-triplet annihilation.
AB  - We report the fluorescent polymer complex which can show fluorescence emission at
      380 nm with the excitation of 520 nm in aqueous media. This photon upconversion
      based on triplet-triplet annihilation can efficiently take place via inter
      molecular energy transfers between the Ru complex as a sensitizer and anthracene
      molecules as an emitter captured into the water-soluble network polymers. We
      performed the oxidation reaction of 2'-deoxyguanosine by riboflavin in the
      presence of the polymer complex with the visible light irradiation. It was
      clearly indicated that oxidative decomposition can be accelerated by UV light
      generation via upconversion based on triplet-triplet annihilation.

PMID- 19749322
TI  - Photochemical generation and reaction of 2'-substituted analogues of C4'-oxidized
      abasic lesion.
AB  - The C4'-oxidized abasic site (1) is one of the oxidatively damaged DNA lesions
      induced by antitumor bleomycins. The reactivity of 1 with amine under neutral
      conditions giving lactam 2 and its structural similarity to unmodified DNA
      suggested the possibility that ODN containing 1 could react with proteins which
      interact with DNA at lysine residue. In order to provide nucleic acid analogues
      with useful lysine modifying reactivity, we planned to study reaction of 2'
      substituted analogues of 1, such as 3-5, with amine and their corresponding caged
      precursors 6-8 were synthesized. Uncaging reaction of 16 containing 6 proceeded
      efficiently. The reaction of obtained 17 containing 3 with Z-Lys-OH did not
      afford products corresponding to lactam. However, HPLC analysis of the reaction
      mixture suggested interaction of 3 with Z-Lys-OH.

PMID- 19749323
TI  - Development of light-responsive BNA toward the spatiotemporal control of gene
      expression.
AB  - We designed and synthesized light-responsive BNA (bridged nucleic acid), which
      has a photolabile group at the bridged structure. Light-Responsive BNA can change
      its structure by a two stages process: photoirradiation followed by nucleophilic
      treatment. In oligonucleotides containing light-responsive BNA moieties, binding
      affinity with complementary single-stranded RNA was lost upon photoirradiation,
      but could be restored by nucleophilic treatment.(1)

PMID- 19749324
TI  - Line up base pairs and intercalators one by one in a stable duplex.
AB  - A stable double helix involving alternating base pairs and azobenzene moieties
      was constructed. In this supramolecule, base pairs and azobenzenes are lined up
      one by one to form an interstrand-wedged motif: each base pair is sandwiched with
      two azobenzenes, and each azobenzene intercalates between two base pairs. This
      motif was formed by the hybridization of two modified DNA tethering multiple
      azobenzene moieties at a frequency of one azobenzene for every two nucleotides.
      Furthermore, this structure could be simply dismantled by UV light irradiation
      and reformed with the irradiation of visible light. By using this new duplex
      motif, construction of a variety of photoresponsive nanostructures and
      nanodevices is highly expected.

PMID- 19749325
TI  - Regulation of duplex DNA strand displacement by visible light sensitive bis
      peptide nucleic acid.
AB  - A novel visible light sensitive azobenzene (AZO) was synthesized and introduced
      into bis-peptide nucleic acid (bis-PNA), which consists of two homopyrimidine PNA
      strands, as a linker. Visible light irradiation of the bis-PNA-AZO conjugate
      induced photoisomerization of the azobenzene moiety from trans to cis. The cis
      form of bis-PNA-AZO displaced the complementary duplex DNA more efficiently than
      the trans-form.

PMID- 19749326
TI  - Photo-switching of vinylpyrene-substituted 2'-deoxyguanosine and its application.
AB  - We synthesized C8-vinylpyrene-substituted 2'-deoxyguanosine (VPy)G and studied
      the photoinduced reversible E-Z isomerization. When E-isomer was irradiated with
      visible light (>420 nm), E- to Z-isomerization took place very rapidly, while
      upon irradiation with UV-light ( approximately 365 nm), Z-isomer was converted to
      E-isomer. When Z-isomer was illuminated with 365- 400 nm light, no fluorescence
      was observed, while E-isomer showed a very strong fluorescence emission,
      indicating that (VPy)G could be a useful fluorescence switching molecule.

PMID- 19749327
TI  - Photo-controllable aptamer.
AB  - We have successfully developed a new method for photoregulation of G-quadruplex
      formation using cis-trans photoisomerization of the photochromic nucleobase
      (8FV)G. Our photo-controllable quadruplexes can be switched between a very stable
      quadruplex state and a non-structured state in a straightforward and reversible
      fashion. We also demonstrated reversibly control binding of a G-quadruplex
      aptamer to thrombin.

PMID- 19749328
TI  - Development of a rapid and reversible photocrosslinking of RNA.
AB  - We describe a novel reversible interstrand photocrosslinking reaction of RNA. In
      this system, a modified oligodeoxynucleotide (ODN) containing 3
      cyanovinylcarbazole nucleoside ((CNV)K) reacts by photoirradiation at 366 nm for
      1 s with pyrimidine residue of a complementary template RNA to yield a
      crosslinked product in 94% yield.

PMID- 19749329
TI  - A selective and sensitive detection of SNP between rice cultivars by using DNA
      photoligation.
AB  - We describe a selective and sensitive single-nucleotide polymorphism (SNP) typing
      of genes from rice cultivars by using DNA photoligation. This SNP typing method
      facilitates qualitative determination of genes from indica and japonica rice, and
      showed a high degree of single nucleotide specificity.

PMID- 19749330
TI  - Photoinduced electron transfer reaction in diaminostilbene-tethered DNA duplexes.
AB  - DNA duplexes containing diaminostilbene (DAS) as a photoinduced electron donor
      were synthesized to investigate mechanisms of electron injection into DNA and the
      succeeding electron transfer in the duplexes. DAS-Capped hairpin DNA showed a
      high structural stability thereby attains large interaction between DAS and the
      terminal base pair. DAS-Tethered DNA by a single linker at the end of the duplex
      was also synthesized and the yields of photoinduced electron transfer through
      mismatched base pairs were quantified. Both duplexes showed similar electron
      transfer efficiencies depending on the base pairs, which suggests DAS stacks well
      on the "pi-way" of the duplex DNA.

PMID- 19749331
TI  - A photochemical detection of methylcytosine by using hydrophobic interaction.
AB  - In this paper, the nonenzymatic detection of 5-methylcytosine with high
      selectivity is described. We present a new methylation detection method by using
      template-directed photoligation through 5-cyanovinyl-2'-deoxyuridine ((C)U).
      Significantly, the photoligation yield of the 5-methylcytosine case was
      approximately 9.1-fold higher than that in the case of cytosine.

PMID- 19749332
TI  - Photoelectrochemical identification of 5-methylcytosine modification in DNA:
      combination of photosensitization and enzymatic cleavage.
AB  - We present a novel photoelectrochemical approach for discriminating between
      cytosine and 5-methylcytosine in DNA when used in combination with enzymatic
      digestion. A photosensitizer-linked DNA duplex bearing 5-methylcytosine or
      cytosine at a given restriction site of the strand was immobilized on a gold
      electrode and digested with enzyme, and the photocurrent response was measured.
      We observed high photocurrent density that was selective for the methylated
      duplex.

PMID- 19749333
TI  - Osmium complex binding to mismatched methylcytosine: effect of adjacent bases.
AB  - We investigated the efficiency of osmium complex formation at 5-methylcytosine in
      mismatched DNA duplexes. Osmium complexation was not observed in fully matched
      duplexes, whereas the complexation site and efficiency in mismatched duplexes
      depended on the 5'-neighboring base of the 5-methylcytosine. In particular, when
      the base adjacent to the 5' side of the mismatched base pair was thymine, a
      unique side reaction was observed. However, the mismatched base pairs did not
      influence the selectivity of osmium complexation with methylated DNA.

PMID- 19749334
TI  - Efficient photooxidative strand cleavage at 5-methylcytosine in DNA by
      sensitization with 9,10-anthraquinone-tethered oligonucleotides.
AB  - Photoirradiation and subsequent hot piperidine treatment of the duplex consisting
      of 5-methylcytosine ((m)C)-containing DNA and 9,10-anthraquinone (AQ)-tethered
      complementary oligodeoxynucleotide led to selective oxidative strand cleavage at
      the target (m)C site, whereas no strand cleavage was observed for the duplex
      containing normal cytosine instead of (m)C. Incorporation of an AQ sensitizer
      into the interior of a strand induced an enhanced one-electron photooxidation,
      presumably because of a much larger intersystem crossing efficiency, leading to
      an efficient strand cleavage at the target (m)C site in DNA. Optimization of the
      photosensitizer could afford more strand cleavage at (m)C in DNA, thereby
      allowing for the more sensitive detection of the target (m)C on a sequencing gel.

PMID- 19749335
TI  - Analysis of an RNA adduct formed from aminophenylnorharman.
AB  - The endogenous mutagenic/carcinogenic 9- (4'-aminophenyl) -9H- pyrido [3,4-b]
      indole (aminophenylnorharman, APNH) is formed from norharman and aniline in the
      presence of cytochrome P-450s. The major APNH-DNA adduct has been reported to be
      2'-deoxyguanosin-8-yl-aminophenylnorhaman (dG-C8-APNH). In addition, demonstrated
      formation of APNH-RNA adduct and conducted a structural analysis using various
      spectrometric approaches. The compound produced from guanosine (Guo) and N
      acetoxy-APNH, an ultimate mutagenic form of APNH, was concluded to be guanosin-8
      yl-APNH (Guo-C8-APNH) on the basis of various spectroscopic analysis. The same
      adduct was found in the livers of rats administered APNH. The total adduct levels
      of APNH-RNA were six times higher than total APNH-DNA adducts in the same rat
      liver samples.

PMID- 19749336
TI  - Fluorescence detection of the endonuclease III reaction using modified
      oligonucleotides.
AB  - We have developed a method for the detection of the endonuclease III reaction by
      fluorescence. The probes were 13-base-pair hairpin-shaped oligonucleotides
      containing one of the isomers of thymine glycol or 5,6-dihydrothymine as a
      damaged base at the center, and had a fluorophore and a quencher at the 5' and 3'
      ends, respectively. Fluorescence was detected when the probe was cleaved by the
      enzyme, because the short fragment bearing the fluorophore could not be
      hybridized to the quencher strand at the incubation temperature. The substrate
      specificity was shown using Escherichia coli and human enzymes.

PMID- 19749337
TI  - Reaction of cytosine with bisulfite and hydroxylamine.
AB  - The synthesis of DNA oligomer containing N(4)-hydroxy-5,6-dihydrocytosine-6
      sulfonate by the simultaneous addition of bisulfite and hydroxylamine under mild
      conditions is reported. To the best of our knowledge, the reaction of the oxime
      into the ketone, N(4)-hydroxy-5,6-dihydrocytosine-6-sulfonate into 5,6
      dihydrouracil-6-sulfonate or uracil has not been reported. Moreover, this issue
      contains the difficulty in specific reactivity of oxime derivative from DNA bases
      include (5m)C toward reagent; for example, T also reacts to potassium
      permanganate known as a reagent for oxime into ketone. Here we examined the
      transformation of DNA containing N(4)-hydroxy-5,6-dihydrocytosine-6-sulfonate
      into 5,6-dihydrouracil 6-sulfonate and the following elimination of sulfonate.

PMID- 19749338
TI  - Progress in the bisulfite modification of nucleic acids.
AB  - Bisulfite modification is a principal tool for analyzing DNA methylation, the
      methyl substitution at position 5 of cytosine residues. Hypermethylation is known
      to cause silencing of genes, which may result in cell function failures. DNA
      methylation analysis is therefore a focus of attention in various fields of
      biological sciences, including even clinical practices for treatment of cancer
      patients. In 2004, we reported that the bisulfite modification of DNA necessary
      in this analysis can be speeded up significantly by using a high concentration
      ammonium bisulfite solution (10 M), in place of traditional sodium bisulfite
      solution of 5 M concentration. Evaluations on this newer protocol have now come
      out from several laboratories, showing that this quick process can yield results
      with greater accuracy compared to those obtainable with widely-practiced low
      concentration methods. Another aspect reported here is a study on the
      desulfonation of uracil-bisulfite adduct to form uracil, the last step of the
      bisulfite-conversion of cytosine to uracil. Kinetic measurements for the
      desulfonation of uridine-bisulfite adduct at a near-neutral pH region are
      described.

PMID- 19749339
TI  - The oxidation of 2'-deoxy-8-oxoguanosine by iodine.
AB  - 8-Oxoguanine is the typical oxidative product, but 8-oxoguanine is further
      oxidized by several oxidizing agents. Here, we investigated the oxidation of 2'
      deoxy-8-oxoguanosine with aqueous iodine.

PMID- 19749340
TI  - Recognition and reaction mechanisms of the (6-4) photolyase as determined by
      using a (6-4) photoproduct analog.
AB  - The (6-4) photoproduct, which is one of the major UV-induced DNA lesions formed
      at bipyrimidine sites, causes carcinogenesis at high frequency. The (6-4)
      photolyases restore the (6-4) photoproducts to their intact bases in a light
      dependent manner, but its overall repair mechanism remains obscure. To
      investigate the light-dependent conversion of the (6-4) photoproduct, we prepared
      a (6-4) photoproduct analog with modification at 3' pyrimidone ring, in which the
      carbonyl group was replaced with an imine to apply to the (6-4) photolyase assay.
      The (6-4) photolyase shows affinity to an oligonucleotide carrying this imine
      analog of the (6-4) photoproduct, though the imine analog is not repaired by the
      (6-4) photolyase.

PMID- 19749341
TI  - Roles of specialized DNA polymerases in mutagenesis by oxidized guanine.
AB  - To assess the involvement of specialized DNA polymerases in the mutagenesis
      induced by an oxidized form of dGTP, 8-hydroxy-2'-deoxyguanosine 5'-triphosphate
      (8-OH-dGTP, 7,8-dihydro-8-oxo-2'-deoxyguanosine 5'-triphosphate), shuttle plasmid
      DNA containing the supF gene and 8-OH-dGTP were introduced into human 293T cells
      in which specialized DNA polymerases were knocked-down by siRNAs. The knock-downs
      of DNA polymerases eta and zeta, and REV1 reduced the A:T-->C:G substitution
      mutations, suggesting that these DNA polymerases are involved in the
      misincorporation of 8-OH-dGTP opposite A. In contrast, the knock-down of DNA
      polymerase tau did not affect the mutations induced by 8-OH-dGTP. The decrease in
      the induced mutation frequency was more evident by double knock-downs of DNA pols
      eta plus zeta and REV1 plus DNA pol zeta (but not by that of DNA pol eta plus
      REV1), suggesting that REV1-DNA pol eta and DNA pol zeta work in different steps.
      These results indicate that specialized DNA polymerases are involved in the
      mutagenesis induced by 8-OH-dGTP.

PMID- 19749342
TI  - Comparison of the activities of bacterial and mammalian nucleotide excision
      repair systems for DNA-protein crosslinks.
AB  - Endogenous and environmental genotoxic agents produce DNA damage and induce cell
      death and mutations. The repair mechanisms of base lesions and single and double
      strand breaks have been well characterized in both prokaryotic and eukaryotic
      cells. However, the molecular pathways that repair or tolerate DNA-protein
      crosslinks (DPCs) remains to be largely elucidated. In this study, we constructed
      DNA substrates containing defined DPCs and assessed the incision activities of
      prokaryotic and eukaryotic nucleotide excision repair systems for DPCs in vitro.

PMID- 19749343
TI  - Accurate curve fitting procedure for UV melting analysis of highly thermostable
      RNA hairpins.
AB  - Thermostable RNA hairpins with specific loop sequences are critically important
      structural elements for proper folding of functional RNAs. Thermodynamic
      parameters of the structural elements are indispensable for secondary structure
      prediction. However when RNA folds into highly thermostable hairpin-loop
      structures, it is difficult to determine the melting temperature and other
      thermodynamic parameters from the normal UV melting analysis. In this study, we
      demonstrate a procedure to solve the problem using our software, Jfit. UV
      absorbance in the higher temperature region above 95 degrees C and the upper
      baseline were estimated using this analytical procedure. The ideal lines of -RlnK
      vs. 1/T were generated from the predicted thermodynamic parameters and the
      solution candidates were compared with the van't Hoff plot generated from the
      measured melting curve to judge their self-consistency. As a result, our analysis
      was able to reduce the number of the possible solution and to specify the best
      set of thermodynamic parameters for the stable hairpin formation.

PMID- 19749344
TI  - Investigations of the cation binding to nucleotides by monitoring the hairpin
      duplex equilibrium of a self-complementary sequence.
AB  - Nucleotide folding accompanies cation binding that shields the electronegative
      potential of phosphate groups, and metal ions in the condensation layer
      predominantly associate diffusely with base-paired nucleotides. Although metal
      ions bound at specific sites have been well studied, information of diffusely
      bound cations, that usually have a weak binding affinity than those associating
      at specific sites, have not been thoroughly studied. We explored a convenient
      experimental system using a self-complementary nucleotide sequence for analyzing
      cationic ligands diffusely bound to DNA or RNA base pairs. To study the metal ion
      nucleotide interaction under a non-homologous aqueous condition, solutions
      containing a large amount of PEG (polyethylene glycol) were examined. We found
      that PEG (e.g., 20 wt%) substantially influenced the metal ion binding to
      nucleotides, suggesting significances of the molecular environment on nucleotide
      cation interactions.

PMID- 19749345
TI  - Synthesis of potent G-quadruplex binders of macrocyclic heptaoxazole and
      evaluation of their activities.
AB  - Guanine-rich DNA sequences form unique three-dimensional conformation known as G
      quadruplexes (G-q). G-q structures have been found in telomere and in some
      oncogene promoter. Recently, it was suggested that G-q showed some biological
      activities including telomere shortening and transcriptional regulation. In this
      paper, we synthesized selective G-q binders and evaluated of their biological
      activities.

PMID- 19749346
TI  - G-quadruplex recognition by macrocyclic hexaoxazole (6OTD) dimer.
AB  - Telomestatin (TMS: 1) is as a potent and selective telomeric G-quadruplex binder.
      Two molecules of TMS were suggested to be intercalated to one telomeric G
      quadruplex according to docking study. In this paper, we designed and synthesized
      hexaoxazole TMS derivative (6OTD) dimer, and evaluated its G-quadruplex
      stabilizing ability.

PMID- 19749347
TI  - Tetraplex structure of budding yeast telomeric DNA.
AB  - We examined the structural properties of budding yeast telomeric DNA sequences,
      SCTELG4: 5'-(TGGG TGTG)(4)-3' and SCTELGG4: 5'-(TGGGTGTGG)(4)-3', in the presence
      of Na(+) or K(+). The conformation of SCTELG4 with Na(+) was a mixture of
      parallel tetraplex DNA and unstructured single-stranded DNA. On the other hand,
      the conformation of SCTELGG4 with Na(+) was a mixture of parallel and
      antiparallel tetraplex DNA. The ratio of the amount of parallel tetraplex to that
      of unstructured single-strand was increased for SCTELG4 by the presence of K(+).
      The conformation of almost all of SCTELGG4 was changed into parallel tetraplex by
      the presence of K(+). These results indicate that structural change of SCTELG4
      and SCTELGG4 may be induced by the type of cation. We conclude that the
      conformation of budding yeast telomeric DNA sequences depends on the base
      sequence and the type of cation.

PMID- 19749348
TI  - Thermal stability and hydration state of DNA G-quadruplex regulated by loop
      regions.
AB  - We designed and synthesized DNA oligonucleotides that were able to fold into
      intramolecular DNA G-quadruplexes with different number of G-quartet planes and
      thymines in the each loop region [GmTn: m indicates the number of G-quartet
      planes (2 <or= m <or= 4), and n indicates the number of thymines in the each loop
      region (2 <or= n <or= 4)]. Effects of molecular crowding on structure of G
      quadruplexes were investigated by circular dichroism spectra in buffers
      containing 0 wt% or 40 wt% PEG200 (poly(ethylene glycol) with an average
      molecular weight of 200). The results showed that G2T2, G2T3, G2T4 and G3T4
      folded into antiparallel G-quadruplexes under the dilute and molecular crowding
      conditions. On the other hand, G3T2, G3T3, G4T2, G4T3, and G4T4 underwent
      structural transitions from antiparallel or mixture to parallel G-quadruplex by
      the addition of PEG200. These result and thermodynamic analysis of G2Tn
      demonstrated that loop regions had pivotal roles to determine structure and
      stability of G-qudruplexes.

PMID- 19749349
TI  - Human telomeric RNA r(UAGGGU) sequence forms parallel tetraplex structure with U
      quartet.
AB  - Recent studies showed that telomere DNAs are transcribed into telomeric-repeat
      containing RNAs in mammalian cells and these RNAs are associated with the
      chromosome ends. Therefore, they may be key components of telomere machinery. We
      have reported that the human telomeric RNA sequence forms parallel G-quadruplex
      structure in the presence of Na(+) ions. In the current study, using a
      combination of CD and NMR experiments, we found that the human telomeric RNA
      r(UAGGGU) sequence can form parallel tetraplex structure with U-quartet in the
      presence of K(+) or Na(+) ions. These results provide valuable information to
      allow understanding of the molecular basis of human telomeric RNA structure.

PMID- 19749350
TI  - Characterization of heme coordination structure in heme-DNA complex possessing
      gaseous molecule as an exogenous ligand.
AB  - We have previously demonstrated that heme, iron(III)-protoporphyrin IX complex,
      and a parallel-quadruplex DNA assembled from d(TTAGGG) form a stable coordination
      complex called "heme-DNA complex". The heme-DNA complex exhibits a variety of
      spectroscopic characteristics remarkably similar to those of met-form of
      myoglobin, oxygen-binding hemoprotein, reflecting that the heme environments in
      the two systems are highly alike to each other. In a course of our effort toward
      exploring functional properties of the heme-DNA complex, we have investigated
      binding of gaseous molecules such as CO and O(2) to the heme-DNA complex. The
      present study revealed that the heme-DNA complex exhibits ability to accommodate
      these molecules as exogenous ligands.

PMID- 19749351
TI  - Interaction between tetraplex structure of yeast telomeric DNA and tetraplex
      binding ligand.
AB  - Fission yeast telomeric DNA sequence, SP4G4: 5'-(GGGGTTAC)(4)-3' has been
      reported to form the antiparallel tetraplex in the presence of K(+). We examined
      the structural properties of budding yeast telomeric DNA sequences, SCTELG4: 5'
      (TGGGTGT G)(4)-3' and SCTELGG4: 5'-(TGGGTGTGG)(4)-3', in the presence of K(+).
      The major conformation of SCTELG4 and SCTELGG4 was a parallel tetraplex DNA. We
      also examined the interaction between tetraplex-binding ligand, TMPyP4, and each
      of the antiparallel tetraplex of SP4G4 and the parallel tetraplex of SCTELG4 and
      SCTELGG4. The ability of TMPyP4 to bind with all of the tetraplexes was observed.
      We conclude that TMPyP4 has the ability to bind with both the parallel and
      antiparallel tetraplex of the telomeric DNA sequences from budding and fission
      yeasts.

PMID- 19749352
TI  - Interaction between tetraplex structure of mouse telomeric DNA and telomeric DNA
      binding domains of mouse telomere binding protein Pot1.
AB  - Mouse telomeric DNA sequence, Tel3.5: 5'-AGGG(T TAGGG)(3)-3', has the ability to
      form antiparallel tetraplex structure in the presence of Na(+). We examined the
      interaction between the antiparallel tetraplex structure of Tel3.5 and each of
      two single-stranded telomeric DNA-binding domains of mouse telomere binding
      protein Pot1, mPot1OB1 and mPot1OB2. The antiparallel tetraplex of Tel3.5 became
      unfolded upon the interaction with mPot1OB1. On the other hand, no significant
      structural change of the antiparallel tetraplex of Tel3.5 was observed upon the
      interaction with mPot1OB2. Considering that the antiparallel tetraplex inhibits
      telomerase-mediated telomere elongation, we conclude that the ability of mPot1OB1
      to unfold the antiparallel tetraplex of the mouse telomeric DNA is required for
      telomerase-mediated telomere elongation.

PMID- 19749353
TI  - Identification of DNA binding specificity for TLS.
AB  - TLS (Translocated in liposarcoma) has been characterized as a rearranged gene in
      chromosomal translocations specific of human myxoid liposarcoma. The various
      cellular functions of TLS participating either in transcription or splicing
      processes are thought the involvement of an interaction of TLS with DNA and/or
      RNA. To investigate insight into DNA-TLS interaction, we performed
      Electrophoretic mobility shift assay of TLS with G-quadruplex DNA. It revealed
      that TLS especially bound to single stranded human telomeric DNA in the presence
      of potassium ion while it was not able to bind double stranded human telomeric
      DNA and single stranded human telomeric DNA in the presence of sodium ion.

PMID- 19749354
TI  - Influence of 3'-azido-2',3'-dideoxyguanosine treatment on telomere length in
      human telomerase-immortalized human fibroblast cells.
AB  - In order to study telomerase activation in normal cells, a telomerase
      immortalized fibroblast cell line, hTERT-BJ1, treated with a telomerase
      inhibitor, 3'-azido-2',3'-dideoxyguanosine (AZddG), is considered to be a good
      model. Long-term treatment with AZddG resulted in telomere shortening from 10-20
      kbp to 5-6 kbp in cultured hTERT BJ1 cells. However, the telomere length then
      stabilized. As expected, removal of AZddG from the culture medium induced
      telomere lengthening in the cells, suggesting that telomerase activity was
      recovered upon AZddG removal. The effect of recovery of telomerase activity in
      hTERT-BJ1 cells will be investigated in future studies.

PMID- 19749355
TI  - Design of cationic graft copolymers as a potential inducer of B-Z transition.
AB  - Biological roles of transition from B form to Z form of DNA (B-Z transition) have
      recently received attention. The B-Z transition was also employed as driving
      machinery of a nano-mechanical DNA device. However, there are little reports of
      effective inducer of the B-Z transition. We previously reported that poly((L)
      Lysine)-graft-dextran induces B-Z transition and grafted dextran plays an
      important role for the B-Z transition. In this report, we designed cationic graft
      copolymer as a potential inducer of B-Z transition. Series of the copolymers
      consisting of poly((L)-Lysine) backbone and abundant of dextran (Dex) or
      poly(ethylene glycol) (PEG) side chains were prepared. The B-Z transition of
      poly(dG-dC)/Poly(dG-dC) were observed in the presence of these copolymers. The
      copolymers having higher content of Dex or PEG effectively induced the B-Z
      transition compared to that having lower content. The result indicated that not
      only electrostatic interaction between DNA and the poly((L)-Lysine) backbone but
      also hydrophilic graft chains play a role for the B-Z transition. We speculated
      that Dex- or PEG-enriched environment is favorable for Z form.

PMID- 19749356
TI  - Release of DNA binary complexes from the ternary complexes by carboxymethyl
      poly(L-histidine).
AB  - The DNA ternary complexes with carboxymethyl poly(L-histidine) (CM-PLH) and
      poly(ethylenimine) (PEI) have released the DNA binary complexes with PEI by the
      protonation of CM-PLH at endosomal/lysosomal pH. The dissociation of the CM-PLH
      from the CM-PLH/PEI/DNA ternary complexes is proved by the fluorescence resonance
      energy transfer (FRET) analysis between the CM-PLH and PEI. The resulting PEI/DNA
      binary complexes easily released DNA, as compared with the CM-PLH/PEI/DNA ternary
      complexes, which was examined by competitive exchange with dextran sulfate. The
      release of the DNA binary complexes from the ternary complexes is promising
      mechanism for higher transfection activity by the CM-PLH/PEI/DNA ternary
      complexes.

PMID- 19749357
TI  - Acridone-labeled DNA aptamer for the detection of biomolecules.
AB  - An acridone-labeled DNA aptamer was synthesized to produce an aptamer probe. This
      aptamer probe could detect a specific molecule based on conformational changes
      upon binding of the specific molecules and the quenching of acridone emission.

PMID- 19749358
TI  - Covalently linked fluorescent ribonucreopeptide sensors.
AB  - Fluorescent biosensors based on the biological macromolecule are convenient tools
      for investigating the event occurring in the living cell. As for one of the
      candidates of such biosensors, we have reported a fluorescent sensor by utilizing
      a ribonucleopeptide (RNP) framework. Fluorescent RNP sensors are obtained from
      the fluorescent RNP library constructed by the combination of the RNA subunit, a
      substrate recognition unit selected by in vitro selection, and a fluorophore
      modified peptide subunit. By taking the advantage of the noncovalent nature of
      fluorescent RNP complexes, RNP sensors with desired optical sensing properties
      are selected in a high-throughput manner. However, the noncovalent nature of the
      fluorescent RNP sensor is not suitable for practical applications. We report here
      a strategy to generate stable covalently linked RNP sensors and demonstrate a
      multiple ligands sensing system by using the covalently linked RNP sensors to
      detect biologically active ligands.

PMID- 19749359
TI  - Structural aspects for the function of ATP-binding ribonucleopeptide receptors.
AB  - We describe here analyses of the secondary structure of ATP-binding
      ribonucleopeptide (RNP) receptors. Mapping of the RNA structure of ATP-binding
      RNP receptors by using hydrolytic enzymes, chemical probing with dimethyl sulfate
      (DMS), and in-line probing indicated that ATP-binding RNP receptors take the loop
      structure at the nucleotide position of the "variable region". In addition, it
      was evident that a part of the consensus region located next to the variable
      region directly participated in the binding to ATP. The completely preserved
      three U nucleotides were essential for the binding of RNP to ATP as revealed by
      the affinity evaluation and the secondary structure analyses of the U nucleotides
      mutants of the ATP-binding RNP receptor. Interestingly, two mutants with an
      adenosine introduced to either of the two U nucleotides showed similar secondary
      structures to the original ATP-binding RNP. These results imply the possibility
      that the adenine base introduced at the U position acts just like the substrate
      ATP, and suggest that the U nucleotides in these positions interact directly to
      ATP.

PMID- 19749360
TI  - Aptazyme-based biosensors using a eukaryotic cell-free translation system.
AB  - I have constructed a novel aptazyme-based biosensor system for detecting
      cofactors of the aptazymes using a cell-free luciferase synthesis in wheat germ
      extract. In this system, the activity of the aptazyme that is fused to a 5'
      untranslated region of a luciferase gene can be detected as luciferase
      expression. In translating the aptazyme-fused mRNA as-is using a wheat germ cell
      free translation system, the luciferase is almost not expressed because of the
      following triple suppression effects: (1) 5'-terminal three bases and (2) 5'
      terminal duplex prevent the ribosome from binding to own mRNA; (3) if the
      ribosome binds, translation of a mimic gene in the aptazyme inhibits that of the
      downstream luciferase gene (OFF state). In contrast, in the presence of the
      aptazyme cofactor, the aptazyme in mRNA is self-cleaved to produce an aptazyme
      free luciferase gene, which is translated efficiently (ON state). The ON/OFF
      efficiency and the detection limit of the aptazyme-based biosensor for
      theophylline are much higher and lower, respectively, compared to those of
      previously-reported one that utilizes a prokaryotic translation system.

PMID- 19749361
TI  - The highly stabilized ribosome display selection of metal binding peptide
      aptamers.
AB  - Development of methods for in vitro selection of peptide aptamers with target
      binding affinities have been expected to construct biocatalysts, biosensors, and
      molecular targeted drugs in leading-edge fields of biotechnology and medical
      therapies. Therefore, a highly stabilized ribosome display method has been
      devised for efficient selection of various peptide aptamers from an artificial
      peptide library (APL). This ribosome display selection is performed by using a
      ribosomal conjugate consisted of APL, Cv RNA-associating protein (Cvap), and mRNA
      having Cv RNA motif at 5' terminus. The conjugate generated by in vitro
      translation can automatically link a peptide as phenotype and its mRNA as
      genotype, which can be stabilized by a high affinity association between Cv motif
      and Cvap. Here, in order to demonstrate the utility of this ribosome display
      method, we performed in vitro selection of peptide aptamers against a metal
      complex, and succeeded in identification and characterization of peptide aptamers
      with specific metal binding affinity. These results validate the concept to
      design APL in DNA level and indicate the versatility of the highly stabilized
      ribosome display selection.

PMID- 19749362
TI  - Characterization of RNA aptamers against SRP19 protein having sequences different
      from SRP RNA.
AB  - SELEX is a conventional method to obtain high affinity nucleic acids to target
      molecules. In this study, high affinity RNA molecules against SRP19 protein were
      selected by using a randomized library. The primary and predicted secondary
      structures of the aptamers are different from those of S-domain RNA which is the
      natural target of SRP19 protein. Comparison of structural features between S
      domain RNA and aptamers might enhance our understanding on RNA-protein
      interaction.

PMID- 19749363
TI  - Structural analysis of ribonucleopeptide aptamer against ATP.
AB  - A ribonucleopeptide aptamer against ATP was obtained by the in vitro selection
      method. This ribonucleopeptide aptamer comprises a randomized and selected RNA
      linked to the Rev-responsive element (RRE) in complex with a peptide derived from
      an HIV Rev protein. The ribonucleopeptide aptamer selectively binds ATP in the
      presence of the Rev-derived peptide, exclusively. Here, we present the structural
      analysis of the ribonucleopeptide aptamer with NMR. The secondary structure of
      the RNA part of the aptamer, the selected RNA region linked to RRE, in the
      presence of the Rev-derived peptide was determined in an Ado-bound form. G:A and
      G:G base pairs, together with canonical base pairs, are formed in a duplex of
      RRE. The selected RNA region plays a crucial role in target binding. It has been
      found that the two U residues located in the selected RNA region trap Ado through
      the formation of the U:A:U base triple. This was directly confirmed by the HNN
      COSY experiment through the detection of spin-spin couplings across the hydrogen
      bonds for Watson-Crick and Hoogsteen A:U base pairs in the U:A:U base triple.

PMID- 19749364
TI  - NMR studies of HAC1 mRNA.
AB  - HAC1 is a transcription factor related to Unfolded Protein Response (UPR)
      signaling in yeast. Processing of HAC1 mRNA on Endoplasmic reticulum (ER) plays a
      key role in UPR signaling pathway, but the recognition mechanism of HAC1 mRNA by
      processing enzyme Ire1p is still unclear. Here, the solution structure of HAC1
      mRNA was investigated by Nuclear Magnetic Resonance (NMR) spectroscopy, focusing
      on the structure of the recognition site of Ire1p in HAC1 mRNA. From the NOESY
      spectrum, imino proton signals of 5' processing regions of HAC1 mRNA were
      assigned and it was found that this region forms the stem-loop structure.

PMID- 19749365
TI  - An isostructural G-G to A-A substitution within the HIV RRE RNA switches the
      specificity towards arginine-rich peptides.
AB  - The HIV Rev protein utilizes a short alpha-helical arginine-rich RNA-binding
      domain to bind deeply within the major groove of an internal loop region of the
      Rev-response element (RRE) RNA. A G48-G71 base-pair which covaries to an
      isostructural A48-A71 base pair has been shown to play an important structure
      role in Rev-RRE binding. On the other hand, a high affinity RRE-binding peptide
      aptamer, the K1 peptide, was shown to have low binding affinity towards the RRE
      A48-A71 mutant, suggesting that the K1 peptide was recognizing the G48-G71 base
      pair. In this study, in an attempt to understand the basis for the recognition of
      the G48-G71 base-pair by the K1 peptide, the selection of peptides that bind to
      the RRE A48A71 (RREAA) mutant was carried out. As a result, a peptide specific
      for the mutant, the LDN1 peptide, was identified. The LDN1 peptide was found to
      bind to the internal loop region of the RREAA, as in the case of the K1-RRE
      interaction. However, amino acids important for LDN1-binding to RREAA, were found
      to be distinct from those important for K1-binding to the RRE. These results
      demonstrate how subtle changes in RNA structure can dramatically alter the
      peptide-binding specificity of an RNA.

PMID- 19749366
TI  - Docking simulation of polyamines on a kissing-loop RNA dimer.
AB  - Polyamines, especially branched polyamines such as tetrakis(3
      aminopropyl)ammonium (Taa), stabilize the tertiary structure of RNA molecules. In
      this study, we examined the polyamine binding site of the HIV-1 dimerization
      initiation site (DIS) in the kissing-loop dimer by the docking simulation. It was
      found that Taa binds predominantly to the kissing loop interaction site of DIS.

PMID- 19749367
TI  - Non-enzymatic in vitro production of circular hammerhead ribozyme targeting the
      template region of human telomerase RNA.
AB  - Circular RNA is more stable than linear RNA both in vitro and in vivo because of
      its inaccessibility to exoribonucleases. Therefore, circularization of functional
      RNAs is a potentially useful methodology for designing therapeutic RNA reagents.
      We designed a circular hammerhead ribozyme that can cleave the template region of
      human telomerase RNA. This circular hammerhead ribozyme was generated by in vitro
      transcription followed by spontaneous self-circularization activity using the
      permuted intron-exon (PIE) method. Two-dimensional gel electrophoresis and
      alkaline digestion of the in vitro transcription products revealed that the
      circular hammerhead ribozyme could be produced by the PIE method. The purified
      circular hammerhead ribozyme cleaved the template region of human telomerase RNA
      in a magnesium-dependent manner. These results indicated that the circular
      hammerhead ribozyme generated by the PIE method maintained the specific feature
      of canonical hammerhead catalytic activity.

PMID- 19749368
TI  - Preparations of hammerhead ribozymes for investigations of their cleavable
      sequences.
AB  - Recently, in hammerhead ribozymes, newly identified loop-loop interaction was
      found to be important for their activation. Therefore, we chemically synthesized
      a hammerhead ribozyme with this extra loop sequences and its mutant ribozymes, as
      well as their substrate RNA strands in order to clarify their cleavable
      sequences. After purification with an anion exchange column chromatography, we
      were able to obtain 44mer and 20mer RNA.

PMID- 19749369
TI  - Multiple-turnover cleavage of double-stranded DNA by sandwiched zinc-finger
      nuclease.
AB  - To refine zinc-finger nuclease (ZFN) technology, we constructed a sandwiched ZFN,
      in which a DNA cleavage enzyme was sandwiched with two artificial zinc-finger
      proteins (AZPs). Because the sandwiched ZFN is designed to cleave the DNA between
      the two AZP-binding sites, the sandwiched ZFN is expected to bind preferentially
      to a DNA substrate rather than to cleavage products and thereby cleave it with
      multiple turnovers. To prove the concept, we sandwiched a staphylococcal nuclease
      (SNase), which cleaves DNA as a monomer, between two 3-finger AZPs. The AZP
      sandwiched SNase cleaved large amounts of dsDNA site-specifically. Such multiple
      turnover cleavage was not observed with control nucleases that possess a single
      AZP.

PMID- 19749370
TI  - Construction of plants resistant to TYLCV by using artificial zinc-finger
      proteins.
AB  - Previously, we have demonstrated that plant DNA virus replication could be
      inhibited in Arabidopsis thaliana by using an artificial zinc-finger protein
      (AZP) and created AZP-based transgenic A. thaliana resistant to DNA virus
      infection. Here we apply the AZP technology to tomato yellow leaf curl virus
      (TYLCV) causing serious damage to an important agricultural crop, tomato. An AZP
      was designed to block binding of the TYLCV replication protein (Rep) to the
      replication origin. The designed AZP had much higher affinities towards the
      replication origin than did the Rep, and efficiently blocked Rep binding in
      vitro. The AZP gene was then introduced into a plant genome with the help of
      Agrobacterium tumefaciens to generate the transgenic plants. The current status
      of the construction of the AZP-expressing transgenic plants will be reported.

PMID- 19749371
TI  - Thymidylate kinase: the lost chemotherapeutic target.
AB  - Here we highlight the unusual substrate specificity of Plasmodium falciparum
      thymidylate kinase (PfTMK) and the validity of the enzyme as a new drug target.
      Furthermore, we predict that the Anaplasma marginale enzyme has attractive domain
      constituents and may be functionally different from other TMPKs. We postulate
      that thymidylate kinases could have multiple attractive functions in pathogens
      and may be a new drug target against numerous microorganisms.

PMID- 19749372
TI  - Inhibition of influenza virus infection by targeting genome conserved region with
      non-natural nucleic acid.
AB  - Two highly conserved 15 base sequences of influenza A virus genome were
      identified by CONSERV software, which can detect contiguous conserved sequences
      of biological sequences. Antiviral effect of phosphorothioate oligonucleotide
      that target these conserved sequences was evaluated by plaque formation assay and
      cell viability assay. Pre-treatment of cells with anti-PB2 (RNA polymerase
      subunit) reduced the size of plaques in a sequence dependent manner. Post
      treatment of cells with anti-PB2 phosphorothioate oligonucleotide inhibited the
      virus-induced cytotoxicity.

PMID- 19749373
TI  - Inhibition of influenza virus by baculovirus-mediated shRNA.
AB  - Influenza viruses A and B cause widespread infections of the human respiratory
      tract; however, existing vaccines and drug therapy are of limited value for their
      treatment. Here we show that bispecific short hairpin small-interfering RNA
      constructs containing an eight-nucleotide intervening spacer, targeted against
      influenza virus A or influenza virus B, can inhibit the production of both types
      of virus in infected cell lines. This multiple vector showed remarkable ability
      to cope with both influenza virus A or B. Furthermore, the Autographa californica
      multiple nuclear polyhedrosis virus can infect a range of mammalian cells,
      facilitating its use as a baculovirus vector for gene delivery into cells. In
      this study, baculovirus-mediated bispecific short-hairpin RNA expression markedly
      inhibited both influenza virus A and B production.

PMID- 19749374
TI  - Regulation of vascular endothelial growth factor gene under hypoxia by using
      artificial transcription factors.
AB  - The vascular endothelial growth factor A (VEGF-A) gene is an attractive
      therapeutic target because both activation and repression of the gene are useful
      for treatment or cure of many diseases related to abnormal angiogenesis. To up-
      or downregulate the endogenous gene expression at will, we previously designed a
      6-finger AZP to recognize a 19-bp target DNA in the VEGF-A gene, and fused the
      AZP with a nuclear localization signal and a transcriptional regulatory domain to
      generate artificial transcription factors (ATFs) for VEGF-A. Using the ATFs, we
      previously demonstrated efficient modulation of the endogenous VEGF-A expression
      under normoxia. In the present study, we examined whether these ATFs modulate the
      endogenous VEGF-A gene expression under hypoxic conditions as well. Enzyme-linked
      immunosorbent assays revealed that the gene-delivered ATFs up- or downregulated
      the VEGF-A expression efficiently under hypoxia.

PMID- 19749375
TI  - Molecular mechanisms of apoptosis induced by 3'-ethynylcytidine.
AB  - 1-(3-C-Ethynyl-beta-D-ribo-pentofuranosyl)cytosine (3'-Ethynylcytidine; ECyd), a
      ribonucleoside analog, has a potent cytotoxic activity against cancer cells. We
      have investigated the cancer-cell death induced by ECyd, focusing on its
      molecular mechanisms. In ECyd-treated cells, RNase L is activated and involved in
      c-jun NH(2)-terminal kinase (JNK) phosphorylation, followed by induction of
      mitochondria-dependent apoptosis. The mechanism of JNK phophorylation by RNase L
      was unknown. To investigate the mechanism, we performed the identification of
      RNase L-binding partners by proteomic approach using co-immunoprecipitation and
      mass spectrometry. We found that RNase L was associated with a protein (we named
      it Protein-190). At the same time, we observed that Protein-190 was amply
      phosphorylated. Furthermore, the participation of Protein-190 in the ECyd-induced
      apoptosis was supported by a knockdown experiment using small interfering RNA
      (siRNA). Thus, the number of ECyd-induced apoptotic cells was drastically
      decreased when Protein-190 was knocked-down. These results indicated Protein-190
      as a regulator in apoptosis, and provide the possibility for a new clinical
      target in cancer chemotherapy.

PMID- 19749376
TI  - Association of nuclear-intermediate filament lamin B1 with necrotic- and
      apoptotic-morphologies in cell death induced by 5-fluoro-2'-deoxyuridine.
AB  - We report that anticancer 5-fluoro-2'-deoxyuridine (FUdR) shows cytotoxicity
      against mouse cancer cell line FM3A cells, using a progeny clone F28-7 and its
      variant F28-7-A. In this process, the cell-death morphology is different between
      F28-7 and F28-7-A cells, that is, necrosis in F28-7 but apoptosis in F28-7-A
      cells. Recently we have investigated the gene and protein expression profiles of
      necrosis and apoptosis induced by FUdR using transcriptomic and proteomic
      analyses. In the proteomic analysis of these cells before their exposure to FUdR,
      the nuclear inner-membrane protein lamin B1 is up-regulated in F28-7 but not in
      F28-7-A, suggesting that lamin B1 may possess a function to regulate the
      morphology of cell-death. A knockdown of lamin B1 expression in F28-7 cells has
      now been performed by use of the small interfering RNA technique, resulting in a
      decrease of the lamin B1-expression level down to the level in F28-7-A.
      Remarkably, the FUdR-induced death morphology of this knocked-down F28-7 was
      apoptosis, definitely different from the necrosis that occurs in the FUdR-treated
      original F28-7. Our present finding provides an interesting possibility that
      lamin-B1 may have an important role in regulating cell-death morphology.

PMID- 19749377
TI  - Preparation of an ochre suppressor tRNA recognizing exclusively UAA codon by
      using the molecular surgery technique.
AB  - In order to create an ochre suppressor tRNA which exclusively recognizes UAA
      codon, we replaced the G34 at the first position of yeast tRNA(Tyr)[GPsiA]
      anticodon with pseudouridine34 (Psi34) by using the molecular surgery technique.
      This tRNA(Tyr)[PsiPsiA] recognized only the UAA codon as expectedly, but
      tRNA(Tyr)[UPsiA] made as a control also behaved similarly. This result may
      suggest that U34 must be somehow modified to facilitate the wobble-pairing to G
      at the third position of codon.

PMID- 19749378
TI  - Screening of amber suppressor tRNAs suitable to introduce nonnatural amino acids
      into proteins by real-time monitoring of cell-free translation.
AB  - Incorporation of nonnatural amino acids into proteins is a useful technique to
      analyze protein structure and function. We have reported that amber suppressor
      tRNAs suitable for efficient and specific incorporation of nonnatural amino acids
      into proteins can be obtained by screening a wide variety of naturally occurring
      tRNAs in an E. coli. cell-free translation system. The amber suppressor activity
      of the tRNAs was evaluated by incorporation of a fluorescent nonnatural amino
      acid and fluorescent SDS-PAGE analysis of cell-free translation products, though
      the SDS-PAGE was troublesome and time-consuming. In this research, we developed
      an alternative method for the screening of amber suppressor tRNAs by real-time
      measurement of fluorescence resonance energy transfer (FRET) from GFP to
      BODIPY558-linked nonnatural amino acid, which was incorporated into the N
      terminus of GFP by amber suppressor tRNAs. Using this method, we demonstrated
      that the screening of the amber suppressor activity of various prokaryotic Trp
      tRNAs was performed in a high-throughput manner.

PMID- 19749379
TI  - Detection of enzymatic activities related to the tRNA splicing pathway in
      Methanosarcina acetivorans cell extract.
AB  - At least two separate enzymes, an endonuclease and a ligase, are thought to be
      involved in the tRNA splicing pathway. The yeast and archaeal endonucleases
      acting in the first step of tRNA splicing commonly produce 2', 3'-cyclic
      phosphate and 5' hydroxy group at the exon-intron borders. Despite this
      similarity in the first step of tRNA splicing, the subsequent mechanism of
      archaeal splicing pathway has not been elucidated yet. We have been searching for
      the archaeal ligase activity from Methanosarcina acetivorans. Here, we report the
      distinct activity of a splicing endonuclease detected in its cell extract.

PMID- 19749380
TI  - Precise analysis of modification status at various stage of tRNA maturation in
      Saccharomyces cerevisiae.
AB  - Transfer RNAs (tRNAs) are decorated with various post-transcriptional
      modifications which are enzymatically introduced at various stages of maturation.
      It is known that eukaryotic tRNAs are modified both in nucleus and cytoplasm.
      However, the order of tRNA modifications remains to be investigated. To unveil
      the precise timing of each modification associated with tRNA processing, we
      isolated precursor forms of Saccharomyces cerevisiae tRNAs at different stages of
      maturation, and analyzed their primary structures including modifications by mass
      spectrometry. The primary transcript of tRNA(Ile) was isolated from the tRNA
      fraction co-precipitated with Lhp1p, a yeast homolog of La protein. The precursor
      tRNA(Ile) without 3'-trailer sequence was isolated from the expression
      controllable strain when RNase P was transiently inactivated. Mass spectrometric
      analyses of these tRNAs revealed that many modifications were fully introduced at
      the stage of primary transcript, however, some modifications were partially
      introduced.

PMID- 19749381
TI  - Production of yeast (m2G10) methyltransferase (Trm11 and Trm112 complex) in a
      wheat germ cell-free translation system.
AB  - Transfer RNA (guanine-N(2)-)-methyltransferase [tRNA (m(2)G10) methyltransferase]
      catalyzes a methyl-transfer from S-adenosyl-L-methionine to N(2)-atom of guanine
      at position 10 (G10) in tRNA and generates N(2)-methylguanine at position 10
      (m(2)G10). Yeast enzyme contains two protein subunits (Trm11 and Trm112). Trm11
      protein is expected to be a catalytic subunit and Trm112 contains a Zinc-finger.
      In yeast cells, Trm112 binds not only to Trm11 but also to other proteins such as
      Lys9, Trm9, and Mtq2. Therefore, the Trm112 protein may regulate population of
      several protein complexes. To address these issues, we started the study on
      synthesis of Trm112 related protein complexes. In this meeting, we report
      synthesis of active Trm11-Trm112 complex in a wheat germ cell-free translation
      system.

PMID- 19749382
TI  - Trans-translation by tmRNA and SmpB.
AB  - tmRNA has a dual function both as a tRNA and an mRNA to facilitate trans
      translation, in which a ribosome can switch translation from a truncated or other
      problematic mRNA to the tmRNA's tag-encoding sequence. During trans-translation,
      tmRNA enters the ribosomal A-site without a codon-anticodon interaction, but with
      an SmpB which is a tmRNA binding protein. To further study the interaction of
      SmpB with ribosome and tmRNA, we have performed directed hydroxyl radical
      probing. It revealed that there are two SmpB binding sites at the A-site and P
      site, and their C-terminal regions reside along the mRNA path in the 30S subunit.
      From these results, we propose a new type of molecular mimicry, in which both
      tmRNA and SmpB mimic the structures and functions of tRNA and mRNA during trans
      translation, addressing how tmRNA preferentially recognizes the stalled ribosome,
      and what substitutes for a codon-anticodon interaction.

PMID- 19749383
TI  - Physiological role of RsgA in ribosome biosynthesis.
AB  - RsgA is a unique GTP hydrolytic protein, in which the GTPase activity is
      significantly enhanced by the small ribosomal subunit. Depletion of RsgA causes
      slow cell growth as well as defects in the subunit assembly of the ribosome and
      the 16S rRNA processing, suggesting its involvement in the maturation of the
      small subunit. Several antibiotics bound to the decoding center of the small
      subunit inhibited the ribosome-dependent GTPase activity of RsgA. Our recent
      study using chemical modification indicates that the binding of RsgA induces
      conformational changes around the A site, P site, and helix 44. These results
      suggest that RsgA is involved in the maturation step of the decoding center of
      the small subunit of ribosome. Here, we also show a physiological role of RsgA
      under stress condition.

PMID- 19749384
TI  - Incipient complex formation between AP endonucleases and DNA containing AP site:
      a vital role of the tryptophan residue.
AB  - To elucidate whether the tryptophan residues in the vicinity of the catalytic
      site are involved in AP site recognition and are critical for AP endonuclease
      activity, the AP endonucleases of the four subtypes in the ExoIII AP endonuclease
      family were characterized and compared the positions of the tryptophan residues.
      The positions of the catalytic amino acid residues, corresponding to Glu-34, Asp
      229, and His-259 of ExoIII, are strictly conserved. On the other hand, the
      positions of the tryptophan residues, which are critical to the incipient complex
      formation, do not exist at a fixed position. There are four patterns at the
      position of the essential tryptophan residue.

PMID- 19749385
TI  - Role of exposed aromatic residues in substrate-binding of CBM family 5 chitin
      binding domain of alkaline chitinase.
AB  - Chitinase J (ChiJ) from alkaliphilic Bacillus sp. strain J813 has a multidomain
      structure containing a catalytic domain (CatD), a fibronectin type III like
      domain (FnIIID) and a chitin-binding domain (ChBD). It has been shown that the
      ChBD binds to an insoluble chitin and enhances its degradation by the CatD.
      Further binding study of the ChBD was performed with a glutathione-S-transferase
      fusion protein. This fusion protein showed binding abilities to insoluble chitin
      and chitosan. Two surface-exposed aromatic residues (Trp541 and Trp542) were
      found in the tertiary-structure model of ChBD and targeted for mutational
      analysis. Single and double mutations of the two aromatic residues decreased the
      chitin- and chitosan-binding abilities. It was revealed that these residues would
      be important for substrate-binding of the ChBD.

PMID- 19749386
TI  - Expression behavior of high-pressure-compacted plasmid DNA in mammalian cell.
AB  - We have been developing a novel compaction method of plasmid DNA using high
      pressure technology, and previously found that the size of the plasmid DNA was
      decreased with increasing the pressurizing-strength and time. In the present
      study, we investigated the tertiary structural change and the expression behavior
      of the pressure-compacted plasmid DNA in cell in vitro. When the pressure
      compacted plasmid DNA was reacted with restriction enzyme (EcoRI), a large amount
      of the EcoRI was required to cleave the pressure-compacted plasmid DNA than the
      non-pressurized plasmid DNA, suggesting that the structural change of plasmid DNA
      was induced by the pressurization. The expression of the pressure-compacted
      plasmid DNA injected into cells using microinjection method was analyzed. It was
      clear that the pressure-compacted plasmid DNA could effectively delay gene
      expression, suggesting that the controlled compaction of plasmid DNA by high
      pressurization would be regulate the transgene expression.

PMID- 19749387
TI  - A novel convenient method for high bacteriophage titer assay.
AB  - The recent various applications of phages (bacteriophages) including phage
      therapy have brought about a revival of phage investigation. The phage titer
      assay is indispensable for phage experiments. However, the conventional standard
      method is a plaque counting method which requires a little skill with tedious
      repeating operation. Furthermore, it is not directly applicable to high phage
      titers. In this paper, we describe a novel convenient "cross streak and paper
      disk assay method" for high titer concentration without plaque counting.

PMID- 19749389
TI  - Should antiretroviral therapy for HIV infection be tailored for intracerebral
      penetration?
AB  - The continuous replication of HIV-1 in the central nervous system, in particular
      the brain, and its potential long-term deleterious effect is the focus of this
      review. Cognitive deficits are observed in a significant percentage of HIV-1
      infected patients. That may occur despite successful peripheral suppression of
      the HIV-1 replication. Compartmentalisation of HIV-1 in the brain, genetic
      mutation of HIV-1, age, HCV coinfection and poor intracerebral penetration, as
      well as possibly a direct toxic effect of antiretroviral drugs, are factors that
      may account for potential creeping damage of the brain after many years of
      treatment. Patients with neurological symptoms or cognitive deficits may require
      another approach to the treatment of their HIV infection.

PMID- 19749390
TI  - A systematic review on the influence of trial quality on the effect of garlic on
      blood pressure.
AB  - BACKGROUND: Garlic is a widely used herbal product for hypertension. Previous
      meta-analyses on the effect of garlic on blood pressure (BP) have been
      contradictory however. We hypothesised that methodological deficiencies may have
      contributed to this disagreement. We therefore evaluated whether trials reporting
      on the effect of garlic on BP had sufficient methodological qualities and a
      proper description of BP determination. METHODS: MEDLINE , EMBASE, AMED, the
      COCHRANE library, IBIDS and CINA HL were systematically searched for trials
      reporting on the effect of garlic on BP. Both the methodological quality and the
      quality of blood pressure measurement were appraised using predefined quality
      scores. RESULTS: 32 Studies were identified. Of these studies, 13 were included
      previously by other meta-analyses. The methodological quality of the studies was
      poor. Only four trials had adequate allocation concealment, no single trial
      reported an intention-to-treat analysis and blinding of the evaluators was done
      in three trials only. Moreover, half of the studies did not report any data on BP
      measurement. No trials reported on the arm level. Body position was described
      most often. All trials fulfilling a predefined cutoff point were conducted in
      normotensive subjects. CONCLUSION: The effect of garlic on blood pressure cannot
      be ascertained. Previous meta-analyses have been based on trials with inadequate
      study designs, methodological deficiencies and with too little information about
      blood pressure measurement. In our view, use of garlic cannot be recommended as
      antihypertensive advice for hypertensive patients in daily practice.

PMID- 19749391
TI  - Impact of anthracycline dose on quality of life and rehabilitation in breast
      cancer treatment.
AB  - BACKGROUND: In 2005 the Dutch national guidelines for treatment of breast cancer
      were updated. From then onwards, patients with operable breast cancer, who
      formerly received four cycles of adjuvant chemotherapy with
      doxorubicin/cyclophosphamide (AC), were treated with five cycles of 5
      fluorouracil/epirubicin/cyclophosphamide (FEC), based on data suggesting survival
      benefit. PRIMARY OBJECTIVE: evaluation of the effect on quality-of-life and
      trainability after four AC versus five FEC cycles of polychemotherapy. SECONDARY
      OBJECTIVE: evaluation of the effectiveness of an 18-week training programme for
      breast cancer survivors. METHODS: A prospective cohort study design was used,
      comparing two chemotherapy regimens historically. The first cohort (group 1)
      received 4AC (A 60 mg/m2, C 600 mg/m2) (n=25) and the second cohort (group 2)
      received 5FE C (F 500 mg/m2, E 90 mg/m2, C 500 mg/m2) (n=50) adjuvant
      polychemotherapy. Both groups completed an 18-week high-intensity strength
      training programme. Outcome measures were changes in quality-of-life (EORTC-QLQ
      C30, MFI -20), muscular strength (one-repetition maximum; leg press) and
      cardiopulmonary function (VO2max) between baseline and follow-up. RESULTS:
      Between March 2002 and February 2006, 75 female subjects with breast cancer
      participated in this study. Baseline characteristics were similar in both groups.
      After completing the training programme, both groups showed a significant
      improvement in all outcome measures. No significant differences in changes of the
      EORTC-QLQ-C30 and MFI-20, one repetition maximum of the leg press and the VO2max
      between the two groups were demonstrated. CONCLUSION: After adaptation of the
      Dutch national breast cancer treatment guidelines, patients received prolonged
      and increased doses of anthracyclines. This, however, did not result in a
      difference in the baseline situation before rehabilitation and in training
      response, nor in quality of life between the two groups.

PMID- 19749392
TI  - Hip surgery sequentially induces stress hyperglycaemia and activates coagulation.
AB  - BACKGROUND: A frequent complication of orthopaedic procedures is venous
      thromboembolism (VTE ). Hyperglycaemia has been shown to activate the coagulation
      system and is associated with postoperative morbidity and mortality. Therefore,
      we hypothesised that glucose levels increase during orthopaedic surgery and are
      associated with an activation of the coagulation system. METHODS: Nine adult
      patients undergoing elective hip replacement were included. Venous blood samples
      were taken before, during and after surgery. Plasma glucose levels, factor VIII
      clotting activity (fVIII:c), von Willebrand ristocetin cofactor activity, von
      Willebrand factor antigen and prothrombin fragment 1+2 were measured. RESULTS:
      Immediately after induction of anaesthesia, plasma glucose levels started to
      increase until the second day postoperatively (peak 8.0 mmol/l). After seven
      weeks glucose values had returned to baseline (6.1 mmol/l), p<0.001 with ANOVA.
      All coagulation parameters increased during surgery, subsequent to the rise in
      glucose. The change in mean FVIII:c and von Willebrand ristocetin cofactor
      activity was significantly correlated with mean glucose values. CONCLUSIONS:
      These observations indicate that total hip replacement surgery causes an increase
      in glucose levels that precedes the proportional rise of the measured coagulation
      parameters. This suggests a possible role of glucose in the activation of the
      coagulation system during hip surgery.

PMID- 19749393
TI  - Splenic rupture following colonoscopy, a rare complication.
AB  - Splenic rupture is an extremely rare complication of colonoscopy. So far, less
      than 80 cases have been reported worldwide since 1970. We report two patients,
      one patient presenting with haemorrhagic shock after a therapeutic colonoscopy
      and another patient presenting with abdominal pain following a diagnostic
      colonoscopy. In both cases splenic rupture was diagnosed by abdominal computed
      tomography (CT scan). One patient was treated by selective embolisation of the
      splenic artery; the other patient underwent a splenectomy. Because the numbers of
      colonoscopies performed in The Netherlands as well as in many other European
      countries are likely to double in the coming years as a result of the
      introduction of nationwide colorectal cancer screening programmes and intensive
      surveillance protocols after polypectomy, more splenic injuries as a complication
      of colonoscopy can be expected in the near future. Awareness of this complication
      is of great importance in early recognition and management of this potentially
      life-threatening injury.

PMID- 19749394
TI  - Laryngeal manifestations of haemochromatosis.
AB  - We present a case with sudden onset of throat pain, dysphagia and hoarseness. On
      endoscopic examination, supraglottic swelling and a brown covering of the mucous
      membranes were seen. The diagnosis of haemochromatosis was made on laryngeal
      biopsy. The patient admitted to long-term iron treatment for anaemia.
      Haemochromatosis can affect many different organs. If the larynx is involved, the
      airway may be endangered.

PMID- 19749395
TI  - Fatal pneumonitis after treatment with docetaxel and trastuzumab.
AB  - Pneumonitis is a rare but serious complication of docetaxel treatment. We report
      a 63-year-old woman with locally advanced breast cancer who was treated with
      docetaxel and trastuzumab. After the first course she was admitted with febrile
      neutropenia that resolved rapidly. After the second course she was admitted again
      with fever and dyspnoea. Despite intensive treatment she died of respiratory
      failure three weeks later. Autopsy showed diffuse interstitial inflammation of
      both lungs consistent with drug-induced inflammation. Docetaxel treatment was the
      most likely cause. It is important to be aware of this toxicity, because the
      subtle warning signs can easily be mistaken for an opportunistic infection, and,
      if not recognised in time, the mortality rate is high.

PMID- 19749396
TI  - Criminal prosecution for the death of patients.

PMID- 19749397
TI  - Acute abdominal pain in a patient receiving enoxaparin.

PMID- 19749398
TI  - Bilateral swollen eyelids occurring during adjuvant treatment with tamoxifen for
      early breast cancer.

PMID- 19749399
TI  - An unexpected cause of iron deficiency detected by capsule endoscopy.

PMID- 19749400
TI  - The spectrum series: grappling with the overlap between Alzheimer's and
      Parkinson's diseases. 9th International Conference on Alzheimer's and Parkinson's
      Diseases, 11-15 March 2009, Prague,Czech Republic.

PMID- 19749401
TI  - Copper abolishes the beta-sheet secondary structure of preformed amyloid fibrils
      of amyloid-beta(42).
AB  - The observation of the co-deposition of metals and amyloid-beta(42) (Abeta(42))
      in brain tissue in Alzheimer's disease prompted myriad investigations into the
      role played by metals in the precipitation of this peptide. Copper is bound by
      monomeric Abeta(12) and upon precipitation of the copper-peptide complex thereby
      prevents Abeta(42) from adopting a beta-sheet secondary structure. Copper is also
      bound by beta-sheet conformers of Abeta(42), and herein we have investigated how
      this interaction affects the conformation of the precipitated peptide. Copper
      significantly reduced the thioflavin T fluorescence of aged, fibrillar Abeta(42)
      with, for example, a 20-fold excess of the metal resulting in a ca 90% reduction
      in thioflavin T fluorescence. Transmission electron microscopy showed that copper
      significantly reduced the quantities of amyloid fibrils while Congo red staining
      and polarized light demonstrated a copper-induced abolition of apple-green
      birefringence. Microscopy under cross-polarized light also revealed the first
      observation of spherulites of Abeta(42). The size and appearance of these amyloid
      structures were found to be very similar to spherulites identified in Alzheimer's
      disease tissue. The combined results of these complementary methods strongly
      suggested that copper abolished the beta-sheet secondary structure of pre-formed,
      aged amyloid fibrils of Abeta(42). Copper may protect against the presence of
      beta-sheets of Abeta(42) in vivo, and its binding by fibrillar Abeta(42) could
      have implications for Alzheimer's disease therapy.

PMID- 19749406
TI  - The neuropathology of older persons with and without dementia from community
      versus clinic cohorts.
AB  - Community-based cohorts of older persons may differ neuropathologically from
      clinic-based cohorts. This study investigated age-related pathologies in persons
      with and without dementia and included autopsied participants from two community
      based cohorts, the Rush Religious Orders Study (n=386) and the Memory and Aging
      Project (n=195), and one clinic-based cohort, the Clinical Core of the Rush
      Alzheimer's Disease Center (n=392). Final clinical diagnoses included no
      cognitive impairment (n=202), mild cognitive impairment (MCI) (n=150), probable
      Alzheimer's disease (AD) (n=474), possible AD (n=88), and other dementias (n=59).
      Postmortem diagnoses included pathologic AD, cerebral infarcts, and Lewy body
      disease. Community-based persons with clinical AD had less severe AD pathology
      (p<0.001) and had more cerebral infarcts (p<0.001) compared to clinic-based
      persons. Additionally, community-based persons with MCI had more infarcts
      compared to clinic-based persons. Overall, there was a higher proportion of Lewy
      bodies and atypical pathologies in the clinic-based compared to the community
      based cohorts (p<0.001). Community-based persons with probable AD show less
      severe AD pathology and more often have infarcts and mixed pathologies; those
      with MCI more often have infarcts and mixed pathologies. Overall, clinic-based
      persons have more Lewy bodies and atypical pathologies. The spectrum of
      pathologies underlying cognitive impairment in clinic-based cohorts differs from
      community-based cohorts.

PMID- 19749407
TI  - A physiological role for amyloid-beta protein:enhancement of learning and memory.
AB  - Amyloid-beta protein (Abeta) is well recognized as having a significant role in
      the pathogenesis of Alzheimer's disease (AD). The reason for the presence of
      Abeta and its physiological role in non-disease states is not clear. In these
      studies, low doses of Abeta enhanced memory retention in two memory tasks and
      enhanced acetylecholine production in the hippocampus in vivo. We then tested
      whether endogenous Abeta has a role in learning and memory in young, cognitively
      intact mice by blocking endogenous Abeta in healthy 2-month-old CD-1 mice.
      Blocking Abeta with antibody to Abeta or DFFVG (which blocks Abeta binding) or
      decreasing Abeta expression with antisense directed at the Abeta precursor,
      AbetaPP, all resulted in impaired learning in T-maze foot-shock avoidance.
      Finally, Abeta 1-42 facilitated induction and maintenance of long term
      potentiation in hippocampal slices, whereas antibodies to Abeta inhibited
      hippocampal LTP. In conclusion, these results indicate that in normal healthy
      young animals the presence of Abeta is important for learning and memory.

PMID- 19749420
TI  - Increased total TAU but not amyloid-beta(42) in cerebrospinal fluid correlates
      with short-term memory impairment in Alzheimer's disease.
AB  - Given the need for tools for early and accurate diagnosis, prediction of disease
      progression, and monitoring efficacy of therapeutic agents for AD, the study of
      cerebrospinal fluid (CSF) biomarkers has become a rapidly growing field of
      research. Several studies have reported conflicting data regarding the
      relationships between CSF biomarkers and dementia severity. In this study, we
      have focused on the identification of CSF biomarkers and their correlations with
      the impairment of different cognitive domains measured using the Cognitive
      Abilities Screening Instrument (CASI). Patients with AD (n=28), non-AD dementia
      (n=16), other neurological disorders (OND, n=14), and healthy controls (HC, n=21)
      were enrolled. Our results revealed significantly higher CSF total tau (t-tau)
      and lower amyloid-beta(42) levels in AD patients compared with those in HC and
      OND groups. Moreover, our data show that CSF t-tau levels, but not Abeta(42)
      levels, have an inverse correlation with the score of short-term memory in CASI
      for patients with AD (Spearman: r=-0.444; p=0.018). This data might indicate that
      the higher CSF t-tau level is associated with more NFT pathology and more severe
      impairment of short-term memory in AD patients.

PMID- 19749430
TI  - Amyloid-beta, tau protein, and oxidative changes as a physiological compensatory
      mechanism to maintain CNS plasticity under Alzheimer's disease and other
      neurodegenerative conditions.
AB  - In this review, we propose that the neurodegenerative changes in the
      neurochemistry of amyloid-beta (Abeta) aggregation, tau phosphorylation,
      cytoskeleton rearrangement, oxidative stress, and lipid peroxidation in
      Alzheimer's disease (AD), and a number of other neurodegenerative diseases, are
      secondary pathological features. In fact, we believe that these phenomena
      represent natural compensatory mechanisms for impaired primary neurodegeneration,
      membrane dynamic deterioration, and/or associated failures of neurotransmission,
      synaptic function, and neuroplasticity. Physiologically, Abeta, lipid
      peroxidation, and tau protein may function to sense changes in activity-dependent
      membrane properties and therefore biochemically modulate membrane lipid
      homeostasis for more efficient synaptic action. As such, the previously proposed
      therapeutic tackling of amyloid, tau, oxidative stress, and other brain disease
      markers may have no ability to cure AD or other devastating central nervous
      system pathologies and peripheral nervous system diseases. This unfortunate
      realization provides a wake-up call to the neuroscience community, demanding open
      minded approach.

PMID- 19749434
TI  - Early biochemical and morphological modifications in the brain of a transgenic
      mouse model of Alzheimer's disease: a role for peroxisomes.
AB  - The central role of peroxisomes in reactive oxygen species and lipid metabolism
      and their importance in brain functioning are well established. The aim of this
      work has been to study the peroxisomal population in the Tg2576 mouse model of
      Alzheimer's disease (AD), at the age of three months when no apparent signs of
      behavioral, neuroanatomical, cytological, or biochemical alterations have been so
      far described. The expression and localization of peroxisomal (PMP70, CAT, AOX,
      and THL) and peroxisome-related proteins (PEX5p, GPX1, SOD1, and SOD2) were
      studied in the neocortex and hippocampus of transgenic and wild-type animals.
      Oxidative stress markers (TBARS, acrolein, and 8-OHG) were also evaluated. Our
      results demonstrate that significant alterations are already detectable at this
      early stage of the disease and also involve peroxisomes. Their number and protein
      composition change concomitantly with early oxidative stress. Interestingly, the
      neocortex shows a compensatory response, consisting in an increase of reactive
      oxygen species scavenging enzymes, while the hippocampus appears more prone to
      the oxidative insult. This different behavior could be related to metabolic
      differences in the two brain areas, also involving peroxisome abundance and/or
      enzymatic content.

PMID- 19749432
TI  - Diminished amyloid-beta burden in Tg2576 mice following a prophylactic oral
      immunization with a salmonella-based amyloid-beta derivative vaccine.
AB  - Immunotherapy holds great promise for Alzheimer's disease (AD) and other
      conformational disorders but certain adverse reactions need to be overcome. Prior
      to the side effects in the first Elan/Wyeth AD vaccine trial, we proposed using
      amyloid-beta (Abeta) derivatives as a safer approach. The route of administration
      may also affect vaccine safety. To assess the feasibility of oral immunization
      that promotes mucosal immunity, Tg2576 AD model mice were treated
      prophylactically three times over 6 weeks starting at 3-5 months of age with a
      Salmonella vaccine expressing K6Abeta(1-30). At 22-24 months of age, cortical
      Abeta plaque burden and total Abeta(40/42) levels were reduced by 48-75% in the
      immunized mice compared to controls, which received unmodified Salmonella. Plaque
      clearance was not associated with increased microglial activation, which may be
      explained by the long treatment period. Furthermore, cerebral microhemorrhages
      were not increased in the treated mice in contrast to several passive Abeta
      antibody studies. These results further support our findings with this immunogen
      delivered subcutaneously and demonstrate its efficacy when given orally, which
      may provide added benefits for human use.

PMID- 19749435
TI  - Pathological-like assembly of tau induced by a paired helical filament core
      expressed at the plasma membrane.
AB  - The hallmark of Alzheimer's disease is the pathological aggregation of tau
      proteins into paired helical filaments and neurofibrillary tangles. This paper
      evaluates the abnormal expression and localization of chimeric tau molecules at
      the plasma membrane of COS-7 cells and its relationship with tau polymerization.
      Overexpression of these proteins, in combination with either tau441 or tau391,
      induces tau to assemble into beta-pleated sheets that are recognized by Thiazin
      red. Immunoelectromicroscopy analysis revealed the presence of filaments close to
      the plasma membrane resembling those found in Alzheimer's disease. The capacity
      of plasma membrane-associated chimeric tau proteins to capture full length tau
      was increased in the presence of H(2)O(2) or okadaic acid treatments. This
      suggests that hyperphosphorylation or an oxidative environment could both
      influence the biochemical properties of the cell that lead to assembly of paired
      helical filaments. The altered localization of tau protein at the plasma membrane
      could play a key role in the assembly of pathological tau.

PMID- 19749436
TI  - Altered cholesterol ester cycle in skin fibroblasts from patients with
      Alzheimer's disease.
AB  - Intracellular cholesterol metabolism was reported to modulate amyloid-beta
      (Abeta) generation in Alzheimer's disease (AD). Results presented herein
      demonstrated that, like brain cells, cultured skin fibroblasts from AD patients
      contained more cholesterol esters than fibroblasts from healthy subjects.
      Particularly, Oil Red-O, Nile Red, and filipin staining highlighted higher levels
      of neutral lipids which responded to inhibitors of acyl-coenzyme A:cholesterol
      acyl-transferase (ACAT-1), associated with an increase in free cholesterol. ACAT
      1 mRNA levels increased significantly in AD fibroblasts, whereas those of sterol
      regulatory element binding protein-2, neutral cholesterol ester hydrolase, and
      ATP-binding cassette transporter member 1 were markedly down-regulated. Instead,
      mRNA levels of low-density lipoprotein receptor, hydroxy-methyl-glutaryl-coenzyme
      A reductase, caveolin-1, and amyloid-beta protein precursor (AbetaPP) were
      virtually unchanged. Notably, mRNA levels of both beta-site AbetaPP-cleaving
      enzyme 1 (BACE1) and neprilysin were significantly down-regulated. An increase in
      Abeta(40) and Abeta(42) immunostaining and a decrease in BACE1 active form were
      also found in AD versus control fibroblasts. Altogether, these findings support
      the hypothesis that the derangement of cholesterol homeostasis is a systemic
      alteration involving central but also peripheral cells of AD patients, and point
      to cholesterol ester levels in AD fibroblasts as an additional metabolic hallmark
      useful in the laboratory and clinical practice.

PMID- 19749438
TI  - Gene expression profiles in the olfactory bulb from a rat model of Alzheimer's
      disease.
AB  - Abnormalities and impaired functions of the olfactory system have been reported
      in Alzheimer's disease (AD), and these changes may appear much earlier than other
      clinical symptoms of AD. However, little is known about these abnormalities at
      the level of gene expression. In this study, we investigated alterations of
      expression of 22,012 genes in the olfactory bulbs of a rat model of AD by using a
      microarray approach. The rat model was produced by intracerebroventricular
      injection of amyloid-beta(25-35), which demonstrated pathological changes in
      olfactory bulbs and memory impairment in the Morris water maze test. We found
      that expression of 811 genes among the 22,012 genes was altered by more than 1.5
      fold in the amyloid-beta-injected rats as compared with control injected rats. We
      analyzed the distribution of the 811 altered genes according to the Affymetrix
      criteria and found that the majority of these genes were related to cellular
      processes, binding, and enzyme activities. The alterations of three of these
      genes, i.e., calcineurin, olfactory receptor, and protein kinase C, were also
      confirmed by RT-PCR and Western blots. These studies provide new insight into the
      abnormalities of the olfactory system in AD and might help to further the
      understanding of the molecular mechanisms of AD.

PMID- 19749437
TI  - Galanin fiber hyperinnervation preserves neuroprotective gene expression in
      cholinergic basal forebrain neurons in Alzheimer's disease.
AB  - Fibers containing galanin (GAL) hyperinnervate cholinergic basal forebrain (CBF)
      nucleus basalis neurons in late stage Alzheimer's disease (AD), yet the molecular
      consequences of this phenomenon are unknown. To determine whether GAL alters the
      expression of genes critical to CBF cell survival in AD, single cell microarray
      analysis was used to determine mRNA levels within nucleus basalis neurons lacking
      GAL innervation from subjects who died with a clinical diagnosis of no cognitive
      impairment (NCI) compared to nucleus basalis neurons from AD cases either lacking
      GAL hyperinnervation (AD/GAL-) or those displaying prominent GAL hyperinnervation
      (AD/GAL+). Levels of mRNAs encoding putatively neuroprotective proteins such as
      the GluR2 Ca(2)-impermeable glutamate receptor subunit, superoxide dismutase 2,
      and the GLUT2 glucose transporter were significantly decreased in AD/GAL- nucleus
      basalis neurons compared to NCI and AD/GAL+ neurons. By contrast, mRNAs encoding
      calpain catalytic and regulatory subunits, which may contribute to cell death in
      AD, were increased in AD/GAL- compared to NCI and AD/GAL+ neurons. Hence, GAL
      fiber hyperinnervation appears to preserve the expression of genes subserving
      multiple neuroprotective pathways suggesting that GAL overexpression regulates
      CBF neuron survival in AD.

PMID- 19749439
TI  - Human truncated tau is using a different mechanism from amyloid-beta to damage
      the blood-brain barrier.
AB  - Recent findings showed that vascular dysfunction is an integral part of
      Alzheimer's disease pathology. Increased microvascular permeability is mainly
      associated with cerebrovascular amyloid-beta deposits. In contrast, little is
      known about the relationship between functional impairment of the blood-brain
      barrier and misfolded tau. In the present study, we examined whether human
      truncated tau is able to impair the blood-brain barrier in an in vitro model. We
      have found that truncated tau induced a very strong polarity-dependent effect in
      the rat blood-brain barrier model. When the tau was added to the upper
      compartment of the model containing endothelial cells (apical treatment), no
      effect was observed. However, the application of tau to the lower compartment
      (basolateral treatment), consisting of astrocyte-microglia culture, triggered
      significant decrease of transendothelial electrical resistance and increase of
      endothelial permeability for mannitol. Further, we found that truncated tau
      showed cytotoxic effects on astrocyte-microglia culture manifested by increased
      extracellular adenylate kinase levels. Molecular analysis of underlying
      mechanisms of tau-induced blood-brain barrier damage revealed the contribution of
      pro-inflammatory cytokine tumor necrosis factor-alpha and chemokine MCP-1
      released from activated microglial cells. This study for the first time uncovers
      a novel toxic gain of function of misfolded tau that could contribute to the
      cerebral microvascular damage in human tauopathies.

PMID- 19749440
TI  - Protein kinase C involvement in the acetylcholine release reduction induced by
      amyloid-beta(25-35) aggregates on neuromuscular synapses.
AB  - Using intracellular recording of the diaphragm muscle of adult rats, we have
      investigated the short-term functional effects of amyloid-beta (Abeta(25-35)
      peptide aggregates on the modulation of acetylcholine (ACh) release and the
      involvement of protein kinase C (PKC). The non-aggregated form of this peptide
      does not change the evoked and spontaneous transmitter release parameters on the
      neuromuscular synapse. However, the aggregated form of Abeta(25-35) acutely
      interferes with evoked quantal ACh release (approximately 40% reduction) when
      synaptic activity in the ex vivo neuromuscular preparation is maintained by low
      frequency (1 Hz) electrical stimulation. This effect is partially dependent on
      the activity of PKC that may have a permissive action. The end result of Abeta(25
      35) is in opposition to the PKC-dependent maintenance effect on ACh release
      manifested in active synapses.

PMID- 19749441
TI  - GOLPH2 gene markers are not associated with Alzheimer's disease in a sample of
      the Spanish population.
AB  - GOLPH2 gene SNP variants Rs10868366 and Rs7019241 were reported to decrease the
      risk of Alzheimer's disease in a recent Whole Genome Association Study. We have
      investigated these genetic variants in 2470 individuals from Spain to conduct an
      independent replication study of the proposed SNP markers. We found no evidence
      of association between GOLPH2 markers and susceptibility to Alzheimer's disease
      in our series. We concluded that GOLPH2 gene does not contribute to risk of
      disease in this study sample.

PMID- 19749442
TI  - Plagiarism in scientific publications.

PMID- 19749443
TI  - The quest for a new vaccine against tuberculosis.
AB  - Tuberculosis (TB) is still one of the deadliest human diseases, killing 1,6
      million people each year, mostly in developing countries. The vaccine currently
      used, Bacille Calmette and Guerin (BCG), is effective in preventing the most
      severe disseminated forms of disease in children and newborns, but its efficacy
      against active TB in adults has been challenged by several clinical studies. It
      is a common opinion that only the development of a new and more effective vaccine
      against TB would significantly ease the pandemic. In the last few years, the
      search for a new vaccine has gained a new momentum. New live and attenuated
      strains of M. tuberculosis, improved recombinant BCG strains and subunit vaccines
      have been tested in preclinical animal models, and some of them showed promising
      results. Unfortunately, the lack of immunological correlates of protection makes
      very difficult to anticipate or foresee the efficacy of any of these new vaccines
      and only phase III clinical trials, that are expected to start in 2009 and last
      few years, will tell us the real value of these new prophylactic tools. This
      review highlights the different strategies that are being implemented for the
      development of an improved vaccine against TB, the rationale behind them and the
      potential and feasible vaccination schedules that could be implemented.

PMID- 19749444
TI  - Drug susceptibility test of Mycobacterium tuberculosis by nitrate reductase
      assay.
AB  - BACKGROUND: Drug susceptibility testing for Mycobacterium tuberculosis (M.
      tuberculosis) is especially required in difficult cases of tuberculosis (TB)
      chemotherapy and in cases of multidrug resistance (MDR-TB; combined resistance to
      isonizid and rifampicin with or without resistance to any other drug). The
      methods for in vitro cultivation and drug susceptibility testing (DST) of M.
      tuberculosis are cumbersome and not readily adaptable in most routine
      laboratories, particularly those in the developing world due to limited resources
      and lack of political will in those countries. A simple and cost effective
      method, the nitrate reductase assay (NRA), was compared with the gold standard
      proportion (egg bases Lowenstein Jensen's [LJ]) method for DST of M. tuberculosis
      in order to substantiate its suitability for routine use in Nigeria and in other
      countries of the developing world with high TB endemicity. METHOD: Drug
      susceptibility test was performed for 70 pulmonary isolates of M. tuberculosis
      (Indirect DST) and 20 sputum (10 acid fast bacilli [AFB] positive and 10 AFB
      negative) specimens (direct DST) by the NRA and the proportion method using
      0.2microg isoniazid (INH), 2microg ethambutol (EMB), 40 microg rifampicin (RIF)
      and 4 microg streptomycin STR). RESULTS: The indirect NRA showed sensitivity and
      specificity for INH: 100% and 100%, EMB: 75% and 100% RIF: 90% and 96.6%, STR:
      66.6% and 91.8%. The results of direct NRA and proportion method for INH, EMB RIF
      and STR agreed 10/10 (100%) for AFB negative specimens and 9/10 (90%) with AFB
      positive specimens. CONCLUSION: Drug susceptibility test of M. tuberculosis by
      the NRA is simple and sensitive with shorter turn around time of 10 to 1 4 days
      compared to 42 days by the LJ proportion method. The direct use of AFB positive
      sputum specimens is likewise reproducible and excludes about 3 - 8 weeks period
      required for isolation of M. tuberculosis .

PMID- 19749445
TI  - Impact of introducing integrated quality assessment for tuberculosis and malaria
      microscopy in Kano, Nigeria.
AB  - BACKGROUND: The World Health Organization (WHO) has recommended the integration
      of malaria microscopy quality assessment (QA) with that of other microscopically
      diagnosed diseases, but there is no evidence that it has been attempted. We
      assessed the feasibility of linking malaria microscopy into the existing
      tuberculosis (TB) microscopy QA system in Kano, Nigeria. METHODOLOGY: Five TB
      microscopy centres were selected for implementing the integrated TB and malaria
      microscopy QA scheme in the state. A model system was designed for selecting and
      blinded rechecking of TB and malaria slides from these laboratories. Supervision
      and evaluation was conducted at 3-month intervals for 24 months. RESULTS: TB
      microscopy QA was strengthened in four laboratories. Full integration of the QA
      for TB and malaria microscopy was achieved in two laboratories, and partial
      integration in two other laboratories. The programme resulted in an increase in
      the specificity of both TB and malaria microscopy results. At the final
      assessment, 100% specificity was achieved for TB microscopy results in four
      laboratories. There was an increased concordance rate and decreased false
      positivity and false negativity rates of TB microscopy results in all five
      laboratories. CONCLUSIONS: It is feasible to integrate the QA system and training
      for TB and malaria microscopy for assessing and improving quality of both
      services. However, the integrated system needs testing in different settings in
      order to be able to develop sound recommendations to guide the complex scaling-up
      process.

PMID- 19749446
TI  - Nontyphoid Salmonella gastroenteritis in pediatric patients from urban areas in
      the city of Merida, Venezuela.
AB  - BACKGROUND: Nontyphoid Salmonella (NTS) infections are a frequent cause of self
      limited diarrhoeal illness in healthy children that do not usually require
      antibiotic treatment. This study was conducted by analyzing the phenotypic and
      genotypic traits of NTS strains from pediatric patients with acute
      gastroenteritis living in urban areas in the city of Merida, Venezuela.
      METHODOLOGY: Thirty-seven Salmonella strains (18 S. Enteritidis; 14 S.
      Typhimurium; 2 S. Java; 2 S. Saintpaul; 1 S. Infantis) were isolated from 243
      stool specimens. These strains were biochemically identified and serotyped.
      Antimicrobial susceptibility was determined by the disc-diffusion assay. Genetic
      characterization included plasmid profiling, PCR detection of the spv region and
      inv genes, and IS200 typing. RESULTS: Thirty (81.0%) of the Salmonella isolates
      were resistant to the antimicrobial tested. Of these strains, 17 (56.7%) were
      resistant to at least one antibiotic. Five resistance patterns were observed, of
      which the most frequently found was the single type (tetracycline, streptomycin
      or ampicillin). All the S. Typhimurium harbored plasmids, but only three large
      plasmids (60, 72 and 84 kb) yielded amplicons with a spvR specific primers. All
      the Salmonella serotypes showed the presence of an inv region. Eight distinct
      IS200 profiles could be detected among the 37 Salmonella strains studied.
      CONCLUSIONS: Predominant Enteritidis and Typhimurium serotypes, as well as
      serotypes Java, Saintpaul and Infantis, are circulating in the city of Merida,
      Venezuela. Most of these strains are susceptible to first-line antibiotics but
      active monitoring of isolates for antimicrobial resistance is necessary. IS200
      typing, applied in association with conventional methods, allowed the
      characterization of all isolates and suggested the presence of different
      infection sources.

PMID- 19749447
TI  - Prevalence and antibiotic-resistance of Salmonella isolated from food in Morocco.
AB  - BACKGROUND: Salmonellosis remains one of the most frequent food-borne diseases
      worldwide, especially in developing countries. The emergence of antimicrobial
      resistance in Salmonella isolates from food can potentially compromise the
      treatment of these infections. This investigation was conducted for the first
      time in Morocco both to detect the occurrence of Salmonella in foods as well as
      to determine the antibiotic resistance profile of the Salmonella isolates.
      METHODOLOGY: In total, 11,516 food samples collected from 2002 to 2005 were
      investigated. Isolated Salmonella were characterized by serotyping and
      susceptibilities were determined for 15 antimicrobial drugs using the disc
      diffusion assay. RESULTS: The overall percentage of Salmonella prevalence (n=105)
      was 0.91% with rates of 71% for slaughterhouses and 9% for seafood. Sixteen
      different serotypes were identified among 104 Salmonella enterica isolates
      including serotypes Infantis (n=25), Bredeney (n=13), Blokley (n=11), Typhimurium
      (n=9), Mbandaka (n=8), Branderup II (n=7), and Kiambu (n=6); 1 isolate of
      Salmonella enterica belonged to subspecies II salamae. Twenty-nine percent of
      isolates (n=30/105) were resistant to at least one antimicrobial. Resistance to
      tetracycline was the most common finding (21%), followed by resistance to
      ampicillin (13%), amoxicillin+clavulanic acid (9%), streptomycin (7%),
      chloramphenicol (4%) and nalidixic acid (3,8%). None of the isolates was
      resistant to 3rd-cephalosporin and fluoroquinolones (i.e. ciprofloxacin).
      Multidrug resistance (MDR) was seen in 9.5% of the isolates, mainly in S..
      Typhimurium DT104 with R-type ACSSuT and S. Hadar. CONCLUSIONS: Despite a low
      frequency of Salmonella isolation, S. Typhimurium DT104 was identified in the
      first step of the food chain. The study points out the need control antibiotic
      resistance in Salmonella isolated from food in Morocco to avoid the spread of
      MDR.

PMID- 19749448
TI  - Isolation, drug resistance and molecular characterization of Salmonella isolates
      in northern Morocco.
AB  - OBJECTIVES: The objective of this investigation was to assess the methods for the
      characterization of Salmonella isolates and to identify relationships of
      Salmonella isolates from human and food sources in northern Morocco. METHODOLOGY:
      Several Salmonella serotypes were isolated from human and food samples and were
      characterized using conventional culture methods, biochemical, serological,
      antimicrobial testing, and phage typing. Molecular analyses such as
      enterobacterial repetitive intergenic consensus (ERIC)-PCR, macrorestriction
      profiling by pulsed-field gel electrophoresis (PFGE), and virulence gene analysis
      were also performed. RESULTS: Sixteen Salmonella strains were isolated in our
      laboratory, serotyped and identified as S. Kottbus, S. Indiana, S. London, S.
      Typhi, S. Hadar, S. Corvallis, S. Mbandaka, S. Ouakam, S. Tm var. cop., S.
      Virchow, and S. Altona. The most common resistance profiles for the isolates was
      ATCFATSCGKSSS, belonging to phage type PT20, ATASCSS associated with strains
      DT104L/ad and ATATSS for isolates that were not typeable. The PFGE patterns were
      different for each Salmonella serotype. All strains were negative for the
      virulence gene spvR. CONCLUSIONS: To our knowledge, this is the first molecular
      characterization of Salmonella in food and humans from Morocco. Comparison of
      molecular techniques for differentiating between human and food isolates of
      Salmonella in north of Morocco shows that ERIC typing and PFGE were more
      discriminating than the other techniques used in this study.

PMID- 19749449
TI  - Influenza vaccination in healthcare workers.
AB  - BACKGROUND: This study aims to determine side effects in healthcare workers
      receiving influenza vaccination, and to scrutinize the opinion of and attitude
      toward vaccination of healthcare workers. METHODS: Five hundred forty-seven
      hospital personnel employed by the Eskisehir Yunus Emre State Hospital were
      included in the study which was conducted in November 2006,. Hospital personnel
      were administered 0.5 ml inactivated influenza vaccine consisting of 2006/2007
      strains. Inoculations were given intramuscularly into the deltoid muscle. A
      specially designated area in the emergency unit was used for the procedure.
      RESULTS: An evaluation on Day 10 following influenza vaccination demonstrated at
      least one adverse effect in 197 (36%) hospital personnel. There was no
      statistical relationship between side effects and age or gender (p=0.860,
      p=0.929), while side effects were significantly more frequent among subjects
      receiving their first vaccination (p=0.008) and nurses (p=0.021). The reasons for
      the lack of prior immunization in 420 (76.8%) HCWs included not considering
      influenza a serious disease in 124 (29.5%), disbelief in the efficacy of
      vaccination in 109 (26%), the lack of reimbursement of vaccination in 105 (25%),
      fear of the side effects of vaccination in 45 (10.7%), preference for other
      methods of protection in 75 (17.9%), and fear of injection in 29 (6.9%).
      CONCLUSIONS: The increase in the rate of influenza immunization among healthcare
      personnel is possible through education, contestation of fear, amelioration of
      misconceptions, solution of financial issues, constitution of a registry system,
      and tracking of vaccination.

PMID- 19749450
TI  - A pilot study on the usefulness of information and education campaign materials
      in enhancing the knowledge, attitude and practice on rabies in rural Sri Lanka.
AB  - BACKGROUND: Rabies remains endemic in Sri Lanka despite a strong government
      patronized anti-rabies campaign. Personal, cultural or religious beliefs have
      been thought to influence health practices that could render rabies prevalent in
      the country. METHODOLOGY: The knowledge, attitudes, and beliefs of 580 household
      heads/members from Nuwara Eliya District, Sri Lanka, regarding rabies were
      explored through a structured questionnaire. An improvement/deterioration in
      their knowledge and practices after the use of information and education campaign
      (IEC) materials was assessed through a repeat exploration at an interval of four
      weeks. RESULTS: Respondents showed inclination toward animal birth control (60%)
      rather than elimination methods (24%). There was disparity between pet owners
      enthusiasm to take pets for rabies inoculation (57%) and their ability to show
      dog vaccination cards (40%). Almost twice more pet owners than non-pet owners
      believed that it is their responsibility to control the population of roaming pet
      dogs (aOR=1.78; 95% CI: 1.14 to 2.76). The rabies leaflets were very effective in
      informing the people on how to deal with rabid animals, the earliest schedule for
      anti-rabies vaccine (ARV), and repeat vaccination. CONCLUSIONS: Awareness and
      proper attitude toward rabies management and canine population control are
      adequate among the rural Sinhalese and Buddhist populations of Sri Lanka;
      however, their current health practices should be improved. The rabies KAP could
      be further enhanced through the use of IEC materials.

PMID- 19749451
TI  - Analysis of a temporal cluster of Shigella boydii isolates in Mpumalanga, South
      Africa, November to December 2007.
AB  - BACKGROUND: Shigellosis is a global human health problem. The disease is most
      prevalent in developing countries with poor access to safe potable water and
      sanitation. Shigella boydii is of particular epidemiological importance in
      developing nations such as African and Asian countries. In the present study, we
      report on the analysis of a temporal cluster of 29 S. boydii serotype 2 strains,
      isolated in the Mpumalanga Province of South Africa (SA) over the period of
      November to December 2007. METHODOLOGY: Bacteria were identified as S. boydii
      using standard microbiological identification techniques and serotyped using
      commercially available antisera. Susceptibility testing to antimicrobial agents
      was determined by the Etest. Genotypic relatedness of strains was investigated by
      pulsed-field gel electrophoresis (PFGE) analysis of digested genomic DNA.
      RESULTS: The cluster of 29 isolates revealed comparable antimicrobial
      susceptibility profiles, while dendrogram analysis of PFGE patterns showed that
      the cluster of isolates grouped together and could clearly be differentiated from
      a random selection of unrelated S. boydii serotype 2 strains. Our data has
      strongly suggested that this cluster of isolates may share a common ancestry.
      However, this cannot be substantiated by epidemiological data because a detailed
      epidemiological investigation was not conducted. CONCLUSIONS: We have documented
      the first cluster of S. boydii infection in SA. Due to the lack of adequate
      epidemiological investigation, we cannot emphatically state that an outbreak had
      occurred. However, we do hypothesis that this was an outbreak for which a
      waterborne source cannot be excluded. This study has highlighted the urgent need
      for timely and appropriate systems of epidemiological investigation of all
      suspected outbreaks of disease in developing countries.

PMID- 19749452
TI  - A case of Actinomycotic mycetoma involving the right foot.
AB  - A 45-year-old male presented with history of multiple swellings over the foot
      with sinuses discharging seropurulent pus. Actinomadura madurae was demonstrated
      and identified by microbiological culture from the pus obtained directly of the
      lesion. This case is reported to emphasize the importance of laboratory diagnosis
      in the management and assessment of the prognosis of such cases.

PMID- 19749453
TI  - Childhood cancers in India: burden, barriers, and breakthroughs.

PMID- 19749454
TI  - Empirical versus theoretical.

PMID- 19749455
TI  - Cisplatin ototoxicity.

PMID- 19749456
TI  - Epidemiology of childhood cancer in India.
AB  - There has been enormous progress in the treatment of childhood cancer in the
      developed world and the epidemiology in these countries is well described.
      Hitherto, there has been no attempt to systematically study the burden of
      childhood cancer in India or to understand how the occurrence and outcome of the
      disease varies across the country. We have reviewed the epidemiology (incidence,
      survival, and mortality) of childhood cancer across different population-based
      cancer registries in India and also compared it with data from the resource-rich
      countries. Incidence and mortality data were obtained from the National Cancer
      Registry Program Reports and the Cancer Incidence in 5 Continents publications.
      Further, a comprehensive review of medical literature was done for information on
      individual cancers as well as survival data. 1.6 to 4.8% of all cancer in India
      is seen in children below 15 years of age and the overall incidence of 38 to 124
      per million children, per year, is lower than that in the developed world. The
      considerable inter-regional variation in incidence and mortality rates across
      India suggests a possible deficiency in ascertainment of cases and death
      notification, particularly in rural areas. The marked male preponderance of
      Hodgkin's disease, lower incidence of central nervous system tumors, and higher
      incidence of retinoblastoma merit further analysis.

PMID- 19749457
TI  - Chemotherapy in adult soft tissue sarcoma.
AB  - Soft tissue sarcomas (STSs) are rare and histologically diverse neoplasms. Recent
      results of various meta-analyses and development of newer drugs have changed the
      medical management of soft tissue sarcoma. This review gives an outline of
      chemotherapy and the newer targeted therapies for the same. We have carried out
      an extensive search in PubMed, Medline for almost all relevant articles
      concerning chemotherapy of soft tissue sarcoma. The available data from the
      literature is mainly composed of the most recent reviews, meta-analyses, phase
      II, and randomized phase III trials published in various peer reviewed journals
      and various international conferences. The role of neoadjuvant and adjuvant
      chemotherapy has been found to be controversial. The recent meta-analysis for
      adjuvant therapy in STSs has shown an increase in the overall survival with
      combination of ifosfamide and adriamycin. In locally advanced and metastatic
      STSs, single agent adriamycin remains the basic standard of medication. The
      combination of ifosfamide and adriamycin may also be used for rapid symptom
      relief and in patients planned for curative resection for metastases. Newer
      combinations of docetaxel and gemcitabine appear promising in selected subgroups,
      especially in leiomyosarcoma and malignant fibrous histiocytoma. Some recent
      developments include the European Union's approval of trabectedin for advanced
      STSs patients who had progressed on adriamycin and ifosfamide therapy. The future
      of mTOR inhibitors, insulin like growth factor receptor inhibitors and anti
      angiogenic drugs appear quite promising. Newer methodologies such as, Bayesian
      adaptive randomization and inclusion of newer end points like progression-free
      rate, time of progression rate, and tumor growth rate will improve the results of
      sarcoma trials. At the end of each section we have also presented recommendations
      from FNx01European Society of Medical Oncology and FNx08National Comprehensive
      Cancer Network guidelines v.1.2009 for better correlation with the present
      literature.

PMID- 19749458
TI  - Pancreatic carcinogenesis: The impact of chronic pancreatitis and its clinical
      relevance.
AB  - Pancreatic cancer is a devastating disease with a dismal prognosis and early
      detection remains a challenge. On the background that inflammation is one of the
      key steps in the development of cancer, it is natural that chronic pancreatitis
      is considered as one of the etiological factors for the development of pancreatic
      cancer. However, the process of pancreatic carcinogenesis is a multifactorial
      phenomenon rather than a process that evolves solely via inflammation. This
      review attempts to put into perspective the association between different
      etiological forms of chronic pancreatitis and pancreatic cancer, and the diverse
      mechanisms operational in the process of pancreatic carcinogenesis. Furthermore,
      the clinical relevance of the current understanding of the relationship between
      chronic pancreatitis and pancreatic cancer, especially with regard to the
      pancreatic head mass of uncertain etiology, is discussed in this review.

PMID- 19749459
TI  - Lipid peroxidation and antioxidants in different stages of cervical cancer:
      Prognostic significance.
AB  - BACKGROUND: Free radical Injury is associated with cancer, but how the extent of
      oxidative stress correlates with the FIGO (International Federation of Gynecology
      and Obstetrics) stage in Carcinoma Cervix (Ca Cx), and its significance as a
      prognostic marker, is not clear and needs an in-depth study. AIM: To correlate
      the blood levels of Lipid Peroxidation (LPO), Reduced Glutathione (GSH),
      Superoxide Dismutase (SOD), and Vitamin A and E levels with the clinical stage in
      Ca Cx. SETTINGS AND DESIGN: This is a Prospective Case Control Study. MATERIALS
      AND METHODS: LPO, SOD, reduced GSH were estimated by Bio Chemical Assays and
      Vitamins by High Performance Liquid Chromatography (HPLC). STATISTICAL ANALYSIS:
      The cases and controls were compared using One Way ANOVA and different stages
      over different time periods were individually compared by Repeated Measure
      Analysis of Variance. RESULTS: The results indicated a statistically significant
      increase of LPO vis-a-vis the FIGO stage of Ca Cx and control, while the
      antioxidant status as depicted by GSH and SOD decreased. Vitamin A and E levels
      were significantly lower in cancer cases as compared to the control. CONCLUSION:
      Increased LPO and reduced antioxidant levels may be taken as associated
      predictive markers, thus suggesting that Ca Cx cases should get nutritive
      supplements to contain the blood LPO level and maintain a positive balance of
      antioxidants for a better outcome in terms of delayed recurrence and better
      Quality of Life (QOL).

PMID- 19749460
TI  - High frequency of loss of allelic integrity at Wilms' tumor suppressor gene-1
      locus in advanced breast tumors associated with aggressiveness of the tumor.
AB  - BACKGROUND: The product of Wilms' tumor suppressor gene (WT1), a nuclear
      transcription factor, regulates the expression of the insulin-like growth factor
      (IGF) and transforming growth factor (TGF) systems, both of which are implicated
      in breast tumorigenesis and are known to facilitate angiogenesis. In the present
      study, WT1 allelic integrity was examined by Loss of Heterozygosity (LOH) studies
      in infiltrating breast carcinoma (n=60), ductal carcinoma in situ (DCIS) (n=10)
      and benign breast disease (n=5) patients, to determine its possible association
      with tumor progression. METHODS: LOH at the WT1 locus (11p13) as determined by
      PCR-RFLP for Hinf1 restriction site and was subsequently examined for its
      association with intratumoral expression of various growth factors i.e. TGF
      beta1, IGF-II, IGF-1R and angiogenesis (VEGF and Intratumoral micro-vessel
      density) in breast carcinoma. RESULTS: Six of 22 (27.2%) genetically heterozygous
      of infiltrating breast carcinoma and 1 of 4 DCIS cases showed loss of one allele
      at WT1 locus. Histologically, the tumors with LOH at WT1 were Intraductal
      carcinoma (IDC) and were of grade II and III. There was no correlation in the
      appearance of LOH at WT1 locus with age, tumor stage, menopausal status,
      chemotherapy status and lymph node metastasis. The expression of factor IGF-II
      and its receptor, IGF-1R was significantly higher in carcinoma having LOH at WT1
      locus. A positive correlation was observed between the TGF-beta1, VEGF expression
      and IMD scores in infiltrating carcinoma. CONCLUSIONS: The current study
      indicates that the high frequency of loss of allelic integrity at Wilms' tumor
      suppressor gene-1 locus in high-graded breast tumors is associated with
      aggressiveness of the tumor.

PMID- 19749461
TI  - Cisplatin-based chemotherapy: Add high-frequency audiometry in the regimen.
AB  - BACKGROUND: Cisplatin-induced ototoxicity shows high interindividual variability
      and is often accompanied by transient or permanent tinnitus. It is not possible
      to identify the susceptible individuals before commencement of the treatment. We
      conducted a prospective, randomized and observational study in a tertiary care
      centre and evaluated the effects of different doses of cisplatin on hearing.
      MATERIALS AND METHODS: Fifty-seven patients scheduled for cisplatin-based
      chemotherapy were included in the study. All patients were divided into three
      groups depending on the dose of cisplatin infused in 3 weeks. RESULTS: The
      subjective hearing loss was found in seven patients, while six patients had
      tinnitus during the chemotherapy. The hearing loss was sensorineural, dose
      dependent, symmetrical, bilateral and irreversible. Higher frequencies were first
      to be affected in cisplatin chemotherapy. CONCLUSION: As use of high-frequency
      audiometry is still limited in research work only, we need a strict protocol of
      adding high-frequency audiometry in the cisplatin-based chemotherapy regimen.

PMID- 19749462
TI  - Comparison of in vitro activities of ceftazidime, piperacillin-tazobactam, and
      cefoperazone-sulbactam, and the implication on empirical therapy in patients with
      cancer.
AB  - BACKGROUND: Infection is a common cause of morbidity and mortality in cancer
      patients. In most of these cases empirical treatment is provided because the
      focus of infection is not identified. Empiric antibiotics provided to these
      patients are based on isolates, sensitivity, and on guidelines. Here we have
      compared three antibiotics recommended as empirical treatment by the Infectious
      Disease Society of America (IDSA). AIMS: To compare the three antibiotic
      sensitivities for gram negative isolates at our institute. OBJECTIVE: To choose
      the optimal antibiotic as the empirical treatment for cancer patients developing
      infections. MATERIALS AND METHODS: We collected the data on isolates and
      antibiotic sensitivity patterns of isolates for ceftazidime, piperacillin +
      tazobactum, and cefoperazone from the medical oncology department. We
      subsequently compared the sensitivity of these three antibiotics. STATISTICAL
      METHODS: The isolates were mapped using the WHONET 5.4 software. The analysis was
      conducted using SPSS 15.0 for Windows. McNemar Chi-square test was used to
      compare the sensitivity percentages between any two antibiotics. The agreement
      between the antibiotic and the gold standard was calculated using the Kappa
      statistic. Two tailed p values were reported. RESULTS: The results showed that
      there was a difference among sensitivities for these antibiotics. It appears that
      the sensitivity of ceftazidime was inferior to the two other antibiotics. Also
      cefoperazone has better sensitivity as compared to piperacillin + tazobactum.
      CONCLUSION: In spite of these three antibiotics being recommended by IDSA our
      data suggest that it should not be followed blindly and local sensitivity data is
      important for formulating institutional guidelines for using antibiotics.

PMID- 19749463
TI  - Distribution of malignant neoplasms reported at different pathology centers and
      hospitals in Jaipur, Rajasthan.
AB  - BACKGROUND: Cancer data from Rajasthan are limited. Only two studies, one from
      Western Rajasthan, and the other from Eastern Rajasthan have been published by
      Sharma et al. in 1992 and 1996. AIMS: To put the cancer profile from this region
      in proper perspective, we conducted the present study on the patterns of various
      malignancies in Jaipur region, i.e., Eastern Rajasthan. SETTING AND DESIGN AND
      MATERIAL AND METHODS: The study spans over one and half decade (1990-2004) and is
      based on a retrospective six-year sample analysis of approximately 200,000
      histopathological and cytological reports for the years 1990, 1991, 1996, 1999,
      2001 and 2004. RESULTS: A total of 21,868 cancers were recorded in the six sample
      years. There were 59.11% (12,926) males and 40.89% (8942) females, with the male
      to female ratio being 1.45:1. Organ wise, lung (8.45%), prostate (7.12%), brain
      (6.04%), urinary bladder (5.31%), esophagus (4.67%) and tongue (4.60%) are most
      common sites involved in males with regard to frequency, whereas breast (20.44%),
      cervix (14.99%), ovary (4.35%), brain (3.80%), esophagus (3.67%), uterus (3.01%)
      and rectum (2.80%) are common sites for malignancies in females. CONCLUSIONS:
      Significant findings were a higher frequency of cancers of the prostate, urinary
      bladder, and brain in males along with gall bladder cancers in females. Our
      figures have been compared with the national data.

PMID- 19749464
TI  - Cancer chemotherapy-induced osteoporosis: How common is it among Saudi Arabian
      cancer survivors.
AB  - OBJECTIVE: This study was done to assess the prevalence of cancer chemotherapy
      induced osteoporosis among survivors of cancer in Saudi Arabia. MATERIAL AND
      METHODS: Patients who received chemotherapy due to malignant disease attending
      oncology and orthopedic clinics between June 1, 2006 and November 30, 2006, were
      the subjects. Age, sex, type of malignancy, last chemotherapy cycle and body mass
      index (BMI) of patients were entered in the database. Complete blood picture,
      serum calcium, phosphorous, renal function and liver function tests were done.
      Bone mineral density measurement of the hip and spine was done using Dual-Energy
      X-ray Absorptiometry. RESULTS: We analyzed the data of 71 patients with an
      average age of 49.29 +/- 8.24 years. Of these, 19 (25.8%) were osteoporotic and
      33.87% were found to be osteopenic according to the BMD of the lumbar spine, 17
      (22.6%) found to be osteoporotic and 29% found to be osteopenic per the BMD of
      the hip area. Patients whose BMD was normal had received their last chemotherapy
      cycle 48.68 +/- 27.35 months earlier (P = 0.01). Osteopenia and osteoporosis were
      more common in patients in the age group of < or =50 years (65.6%) versus 56.4%
      in patients of > or =51 years (P = 0.001). Patients who received the last cycle
      of chemotherapy of less than 2 years were significantly more osteoporotic (81.5%
      18.5%, P < 0.0001). CONCLUSIONS: Our study indicates a high prevalence of
      osteopenia and osteoporosis in patients who were younger than < or =50 years and
      who had received cancer chemotherapy. Second, bone loss continued for more than 2
      years from the last cycle of chemotherapy.

PMID- 19749465
TI  - Analysis of binding energy activity of imatinib and Abl tyrosine kinase domain
      based on simple consideration for conformational change: An explanation for
      variation in imatinib effect in mutated type.
AB  - Imatinib is a clinically well-tolerated small molecule inhibitor that exerts
      selective, dual inhibition on the transforming growth factor beta and platelet
      derived growth factor pathways. The recognition of an inactive conformation of
      Abl, in which a catalytically important Asp-Phe-Gly motif is flipped by
      approximately 180 degrees with respect to the active conformation, underlies the
      specificity of the cancer drug imatinib, which is used to treat chronic
      myelogenous leukemia. However, conformational analysis shows that the effect of
      the drug depends on the potential energy, which varies due to the alpha rotatable
      angles of the Abl tyrosine kinase domain. In this study, the author determines
      the change of binding energy between the Abl tyrosine kinase domain, due to the
      variation in rotatable angles, and bond lengthening. According to this study, the
      ratio between the required binding energy between the wild and mutated types is
      equal to 1: 1.16.

PMID- 19749466
TI  - Mechanical lymphatic drainage in the treatment of arm lymphedema.
AB  - Exercising is one of the three cornerstones in the treatment of lymphedema
      together with contention mechanisms and lymphatic drainage. The aim of the
      current study was to evaluate a new method of mechanic lymphatic drainage.
      Volumetric reductions were evaluated after passive exercises in 25 patients with
      arm lymphedema resulting from breast cancer treatment. Their ages ranged between
      42 and 86 years old. All patients were submitted to one-hour sessions using the
      RAGodoy electromechanical apparatus which performs from 15 to 25 elbow bending
      and stretching exercises per minute. Volumetry, using the water displacement
      technique, was performed before and after the sessions. The paired t-test was
      employed for statistical analysis with an alpha error of less than 5% being
      considered acceptable. The reduction in volume was significant (P-value < 0.001)
      with a mean initial volume of 2026.4 and final volume of 1967.2 giving a mean
      loss of 59.2 mL. The RAGodoy apparatus was efficient to reduce the volume of
      lymphedematous arms and is an option for the treatment of lymphedema.

PMID- 19749467
TI  - Primary malignant melanoma in cystic teratoma of ovary.

PMID- 19749468
TI  - Cancer control in India- A sorry state.

PMID- 19749469
TI  - Bilateral breast metastases in a pregnant woman with disseminated cutaneous
      melanoma.

PMID- 19749470
TI  - Paget's disease of breast masquerading as chronic benign eczema.

PMID- 19749471
TI  - Primary malignant melanoma of anorectum: A rare entity.

PMID- 19749472
TI  - Role of fine needle aspiration cytology in preoperative diagnosis of
      ameloblastoma.

PMID- 19749473
TI  - Complete clinical and pathological response to preoperative short course
      radiotherapy in T 2 rectal cancer.

PMID- 19749474
TI  - Breast cancer incidence among females in the Golestan province, Iran.

PMID- 19749475
TI  - Primary neuroendocrine carcinoma of the breast, which chemotherapy?

PMID- 19749476
TI  - Subcutaneous metastasis in esophageal carcinoma detected by FDG-PET Imaging.

PMID- 19749477
TI  - Atrial function during different multisite atrial pacing modalities in patients
      with bradycardia--tachycardia syndrome.
AB  - BACKGROUND: Multisite atrial pacing (MAP) was introduced to improve atrial
      electrical synchrony and prevent recurrence of atrial fibrillation (AF). METHODS
      AND RESULTS: In the present study there were 57 patients with sinus node disease,
      AF recurrence and prolonged P-wave on ECG with 2 MAP modalities. In all patients
      1 lead was implanted in the coronary sinus (CS) ostium area. In the right atrial
      appendage (RAA)+CS group (28 patients) the other atrial lead was in the RAA, and
      in the BB+CS group (29 patients) in the Bachmann's bundle (BB) region. Tissue
      Doppler was used to register the electromechanical delay (EMD) in the atrial
      walls and estimate the atrial contraction synchrony. Cardiac output and
      myocardial performance index did not differ during the 2 MAP modalities. During
      BB+CS, in comparison with RAA+CS pacing, the peak of the mitral atrial wave
      occurred earlier (P<0.01), the usual right-left atrial contraction sequence was
      reversed more frequently (P<0.004), all atrial EMDs except for the lateral left
      atrium (LA) were shorter (P<0.05), and LA synchrony was greater (P<0.001).
      CONCLUSIONS: In patients treated with MAP, implanting 1 of the atrial leads in
      the BB area instead of the RAA has no influence on global cardiac hemodynamics,
      but does result in earlier LA contraction, and reversal of the typical right-left
      atrial contraction sequence, as well as providing greater LA contraction
      synchrony.

PMID- 19749478
TI  - Angiotensin II receptor blocker, valsartan, increases myocardial blood volume and
      regresses hypertrophy in hypertensive patients.
AB  - BACKGROUND: Although a reduction in myocardial blood volume (MBV), an in vivo
      index of the myocardial microvasculature, measured by myocardial contrast
      echocardiography in patients with hypertension (HT), can be demonstrated, it is
      still unknown whether a decreased MBV can be improved by antihypertensive
      treatment. METHODS AND RESULTS: Eleven HT patients (mean age 58 years, 7 men)
      with left ventricular hypertrophy (LVH) and 10 age- and sex-matched normal
      controls were studied. Harmonic power Doppler images were acquired at end
      diastole of every 6(th) beat and MBV was calculated as 10(X/10)x100%, where X
      (dB) is myocardial contrast intensity minus the contrast intensity of the
      adjacent intracavity blood pool. Baseline blood pressure (BP) and left
      ventricular mass index (LVMI) in the HT patients were higher and MBV was lower
      than in the controls (2.52 +/-0.37% vs 3.31 +/-0.61%, P<0.01). MBV did not
      correlate with mean BP, but was inversely correlated with LVMI (r=0.61, P<0.01).
      After treatment with valsartan for 6 months, LVMI significantly decreased and MBV
      increased (2.72 +/-0.26%, P<0.05 vs baseline) in the patients with HT. There was
      a significant inverse correlation between the changes in MBV and those of LVMI
      (r=0.62, P<0.05), but not between MBV and mean BP. CONCLUSIONS: Valsartan, an
      angiotensin II receptor blocker, corrected the decreased MBV in association with
      regression of LVH in patients with HT.

PMID- 19749479
TI  - Clinical outcomes of sirolimus-eluting stenting after rotational atherectomy.
AB  - BACKGROUND: The efficacy of drug-eluting stents after rotational atherectomy
      (ROTA) has not been clarified. METHODS AND RESULTS: The 704 consecutive patients
      who underwent percutaneous coronary intervention (PCI) with a sirolimus-eluting
      stent (SES) (79 with and 625 without ROTA) were enrolled. The 2-year clinical
      outcome of these patients was compared with that of a group of 1,123 consecutive
      patients treated with bare-metal stents (BMS) (144 with and 979 without ROTA). At
      2 years after index PCI, the use of SES after ROTA was associated with a lower
      crude incidence of major adverse cardiac events (MACE) than were BMS after ROTA
      (30.1% vs 43.1%, P=0.024). The difference was mainly derived from the reduction
      in target lesion revascularization (TLR) (25.0% vs 39.1%, P=0.022). After
      adjusting for confounders, ROTA-SES was associated with a reduction in MACE and
      TLR, with a similar hazard ratio to the non-ROTA group only with SES
      implantation. In a subgroup of dialysis patients, the incidence of TLR after ROTA
      with SES and BMS was similarly high. CONCLUSIONS: The use of SES after ROTA is an
      appropriate method for selected hard lesions, but has a limited effect in
      dialysis patients, even after lesion preparation with ROTA.

PMID- 19749480
TI  - Antioxidant, EUK-8, prevents murine dilated cardiomyopathy.
AB  - BACKGROUND: Mice lacking manganese-superoxide dismutase (Mn-SOD) activity exhibit
      the typical pathology of dilated cardiomyopathy (DCM). In the present study,
      presymptomatic and symptomatic mutant mice were treated with the SOD/catalase
      mimetic, EUK-8. METHODS AND RESULTS: Presymptomatic heart/muscle-specific Mn-SOD
      deficient mice (H/M-Sod2(-/-)) were treated with EUK-8 (30 mg x kg(-1) . day(-1))
      for 4 weeks, and then cardiac function and the reactive oxygen species (ROS)
      production in their heart mitochondria were assessed. EUK-8 treatment suppressed
      the progression of cardiac dysfunction and diminished ROS production and
      oxidative damage. Furthermore, EUK-8 treatment effectively reversed the cardiac
      dilatation and dysfunction observed in symptomatic H/M-Sod2(-/-) mice.
      Interestingly, EUK-8 treatment repaired a molecular defect in connexin43.
      CONCLUSIONS: EUK-8 treatment can prevent and cure murine DCM, so SOD/catalase
      mimetic treatment is proposed as a potential therapy for DCM.

PMID- 19749481
TI  - Chemical-mechanical synergism for cardiovascular TRPC6 channel activation via
      PLC/diacylglycerol and PLA2/omega-hydroxylase/20-HETE pathways.

PMID- 19749482
TI  - Involvement of TRPM2 channel in amplification of reactive oxygen species-induced
      signaling and chronic inflammation.

PMID- 19749483
TI  - Pathological role of TRP channels in cardiovascular and respiratory diseases.

PMID- 19749484
TI  - Regulation of cardiac hypertrophy by the formation of G protein-coupled receptor-
      TRPC channel protein complex.

PMID- 19749485
TI  - Assessment of attentional function and impulsivity using 5-choice serial reaction
      time task/3-choice serial reaction time task.

PMID- 19749486
TI  - Impact of intestinal metabolism on drug development.

PMID- 19749487
TI  - Drug metabolism catalyzed by cytochrome P-450.

PMID- 19749488
TI  - Pharmacological profile and clinical efficacy of minodronic acid hydrate as a new
      therapeutic agent for osteoporosis.

PMID- 19749489
TI  - Pharmacological properties and clinical efficacy of dasatinib hydrate (Sprycel),
      an anticancer drug for chronic myelogenous leukemia and Philadelphia chromosome
      positive acute lymphoblastic leukemia.

PMID- 19749490
TI  - Effects of exercise training on circulating high molecular weight adiponectin and
      adiponectin oligomer composition: a randomized controlled trial.
AB  - AIM: To determine the effects of exercise training on total and high molecular
      weight (HMW) adiponectin and adiponectin oligomeric distribution. METHODS: A
      randomized parallel-design study (n=53; 40 women and 13 men; age range, 32?65
      years) was conducted at a fitness club between April 2006 and July 2007.
      Participants were randomly assigned to the exercise (n=26) or control (n=27)
      group and received exercise training for 70 min 2 times per week for 12 weeks and
      exercise advice at the baseline, respectively. The primary outcomes were changes
      in total adiponectin, HMW adiponectin and percentage of HMW adiponectin. RESULTS:
      Muscle strength improved in the exercise group but remained stable in the control
      group. Body weight and BMI were not modified by exercise training. After 12
      weeks, there were no differences between groups in total adiponectin levels, HMW
      adiponectin levels, or percentage of HMW adiponectin. CONCLUSION: In the absence
      of weight loss, twice-weekly exercise training does not change HMW adiponectin
      levels or the adiponectin oligomer composition.

PMID- 19749491
TI  - High-sensitivity CRP reflects insulin resistance in smokers.
AB  - AIM: The elevation of high-sensitivity C-reactive protein (hs-CRP) is a strong
      risk factor for cardio-vascular disease (CVD) and is associated with insulin
      resistance. The hs-CRP concentration also increases in smokers known to be at a
      high risk for CVD. We examined whether hs-CRP concentra-tion reflects insulin
      resistance in smokers. METHODS: The hs-CRP levels were measured in 121 male
      subjects (54 nonsmokers and 67 smokers) with a normal glucose tolerance. The hs
      CRP concentration was compared to the homeostasis model assessment of insulin
      resistance (HOMA-IR) and other clinical variables related to insulin resistance.
      RESULTS: Smokers had a 64.5% higher hs-CRP concentration than nonsmokers
      (p<0.0001). In both nonsmokers and smokers, hs-CRP positively correlated with
      HOMA-IR (r=0.301, p<0.05 and r=0.312, p<0.01) and fasting insulin (r=0.281,
      p<0.05 and r=0.356, p<0.01). The correlation between hs-CRP and HOMA-IR or
      fasting insulin was stronger in smokers than in nonsmokers. In smokers, hs-CRP
      significantly correlated with BMI and HDL-cholesterol (r=0.386, p<0.01 and r=
      0.307, p<0.05). Stepwise regression analysis revealed that BMI and HOMA-IR were
      significant predictors of hs-CRP in smokers (r=0.423, p<0.01). CONCLUSIONS: The
      hs-CRP concentration reflects insulin resistance in smokers. It would be
      preferable to consider insulin resistance in evaluating hs-CRP concentrations,
      even in smokers.

PMID- 19749492
TI  - Intima-media thickness of lower-limb arteries associated with fasting and post
      challenge plasma glucose levels.
AB  - AIM: Atherosclerosis is a systemic disease with focal cardiovascular events.
      Although the accelerated development of peripheral arterial disease in diabetic
      patients is well known, the pathogenic mechanism of site-specific susceptibility
      to glycemia is uncertain. OBJECTIVE: To investigate the association of fasting
      and post-challenge glucose levels with intima-media thickness (IMT) at different
      arterial sites. METHODS: Forty consecutive middle-aged volunteers aged 37 to 53
      years were recruited to define the association of IMT with cardiovascular risk
      factors at 12 carotid and 6 lower-limb arterial sites. A linear mixed model was
      used to regress the primary outcome measures, which were repeated measures of IMT
      at multiple arterial sites (18 sites per participant), on fixed-effect predictors
      of various conventional cardiovascular risk factors, while accounting for the
      interdependence of repeated measures taken from the same participant with
      unstructured covariance. RESULTS: Carotid IMTs were associated independently with
      waist circumference and systolic blood pressure, whereas lower-limb IMTs were
      associated with waist circumference, low-density lipoprotein cholesterol (LDL-C),
      glycated hemoglobin A1C (HbA1C), and fasting and 2-hour post-challenge plasma
      glucose levels; these associations were stronger in overall arteries. Independent
      associations of ALT and smoking with IMT appeared only in overall arteries.
      CONCLUSION: In a middle-aged, nonclinical sample, lower-limb but not carotid IMTs
      are associated independently with HbA1C, and fasting and 2-hour post-challenge
      plasma glucose levels.

PMID- 19749493
TI  - Associations between blood lipid profiles and risk of myocardial infarction among
      Japanese male workers: 3M Study.
AB  - AIM: To examine whether fasting blood lipid profiles are associated with the risk
      of myocardial infarction among Japanese men. METHODS: We conducted a nested case
      control study in the Morbidity of Myocardial Infarction Multicenter Study in
      Japan (3M Study). For each case of myocardial infarction entered in the 3M Study
      between 1997 and 2000, we randomly selected two controls, matched for age (+/-3
      years), from among the participants in risk factor surveys with no history of
      myocardial infarction. A total of 723 male employees (241 cases and 482 controls)
      aged 35 to 65 years were enrolled in the present study. RESULTS: The subjects had
      significantly higher mean fasting LDL-cholesterol and triglyceride, and lower
      mean HDL-cholesterol than controls. The multivariable conditional odds ratio (95%
      confidence interval) for myocardial infarction after adjustment for known
      cardiovascular risk factors was 3.87 (1.27-11.7, p for trend <0.001) for total
      cholesterol [-6.71 vs <4.65 mmol/L], 3.28 (1.12-9.60, p for trend=0.001) for LDL
      cholesterol [-4.64 vs <2.59 mmol/L], 0.17 (0.07-0.43, p for trend=0.001) for HDL
      cholesterol [-1.55 vs <1.03 mmol/L] and 3.03 (1.37-6.70, p for trend= 0.01) for
      triglycerides [-2.26 vs <1.13 mmol/L]. CONCLUSION: High total and LDL
      cholesterol, low HDL-cholesterol and high triglycerides levels were independently
      associated with an increased risk of myocardial infarction among middle-aged
      Japanese male workers.

PMID- 19749494
TI  - Protective effects of efonidipine, a T- and L-type calcium channel blocker, on
      renal function and arterial stiffness in type 2 diabetic patients with
      hypertension and nephropathy.
AB  - AIM: The three types of calcium channel blocker (CCB), L-, T- and N-type, possess
      heterogeneous actions on endothelial function and renal microvascular function.
      In the present study, we evaluated the effects of two CCBs, efonidipine and
      amlodipine, on renal function and arterial stiffness. METHODS: Forty type 2
      diabetic patients with hypertension and nephropathy receiving angiotensin
      receptor II blockers were enrolled and randomly divided into two groups: the
      efonidipine group was administered efonidipine hydrochloride ethanolate 40 mg/day
      and the amlodipine group was admin-istered amlodipine besilate 5 mg/day for 12
      months. Arterial stiffness was evaluated by the cardio-ankle vascular index
      (CAVI). RESULTS: Changes in blood pressure during the study were almost the same
      in the two groups. Sig-nificant increases in serum creatinine and urinary albumin
      and a significant decrease in the esti-mated glomerular filtration rate were
      observed in the amlodipine group, but not in the efonidipine group. On the other
      hand, significant decreases in plasma aldosterone, urinary 8-hydroxy-2'-deoxy
      guanosine and CAVI were observed after 12 months in the efonidipine group, but
      not in the amlo-dipine group. CONCLUSIONS: These results suggest that
      efonidipine, which is both a T-type and L-type calcium chan-nel blocker, has more
      favorable effects on renal function, oxidative stress and arterial stiffness than
      amlodipine, an L-type calcium channel blocker.

PMID- 19749495
TI  - Roles of oxidative stress and redox regulation in atherosclerosis.
AB  - Oxidative stress is believed to be a cause of aging and cardiovascular disorders.
      In response to inflam-mation or endothelial cell injury, production of reactive
      oxygen species (ROS) is enhanced in vascular cells. These changes contribute to
      the initiation of atherosclerosis. Vascular cells possess anti-oxidant systems to
      protect against oxidative stress, in addition to the redox system. The redox
      status of pro-tein thiols is important for cellular functions. The Akt signaling
      pathway exerts effects on survival and apoptosis, and is regulated by the
      glutathione (GSH)/glutaredoxin (GRX)-dependent redox sys-tem. Sex hormones such
      as estrogens protect against oxidative stress by protecting the Akt signaling
      pathway but the physiological role of the extracellular GSH/GRX system has not
      been clarified, although found an increase in the levels of S-glutathionylated
      serum proteins in patients with athero-sclerosis obliterans. The results
      suggested that impaired serum redox potential is a marker of the development
      vascular dysfunction and estrogen has a possible role in the prevention of
      atherosclerosis.

PMID- 19749496
TI  - Effects of different statin treatments on small dense low-density lipoprotein in
      patients with metabolic syndrome.
AB  - AIM: To compare the effects of different low-density lipoprotein (LDL)
      cholesterol-lowering statin treatments on small dense LDL (sd-LDL) in
      hypercholesterolemic patients with metabolic syndrome (MetS). METHODS: Forty
      hypercholesterolemic MetS patients ?30 years of age were randomized to rosuvas
      tatin (n=17) or other statins (n=23) groups. In the other statins group, those
      taking atorvastatin (n=12) were also evaluated separately. Statin doses were 10
      mg/day rosuvastatin, 20 mg/day atorvas-tatin, 40 mg/day simvastatin, and 40
      mg/day pravastatin. Treatment duration was planned to be 8 weeks. Sd-LDL levels
      were assessed at baseline and at the completion of treatment. RESULTS: After
      treatment, sd-LDL levels were significantly reduced in all 3 groups (from 29.6+/
      24.8 mg/dL to 8.9+/-8.5 mg/dL in the rosuvastatin group, p=0.001; from 26.2+/-15
      mg/dL to 14.8+/-9.6 mg/dL in the atorvastatin group, p=0.02; and from 29.1+/-16.5
      mg/dL to 14.7+/-11.2 mg/dL in the other statins group, p=0.0001). There was no
      significant difference in the mean percent changes among groups. CONCLUSION:
      Significant reduction in sd-LDL levels was observed after 8 weeks of statin
      treatment in hypercholesterolemic patients with MetS. This effect was similar for
      all statins and can be considered a class effect.

PMID- 19749497
TI  - Development and evaluation of a questionnaire for measuring suboptimal health
      status in urban Chinese.
AB  - BACKGROUND: Suboptimal health status (SHS) is characterized by ambiguous health
      complaints, general weakness, and lack of vitality, and has become a new public
      health challenge in China. It is believed to be a subclinical, reversible stage
      of chronic disease. Studies of intervention and prognosis for SHS are expected to
      become increasingly important. Consequently, a reliable and valid instrument to
      assess SHS is essential. We developed and evaluated a questionnaire for measuring
      SHS in urban Chinese. METHODS: Focus group discussions and a literature review
      provided the basis for the development of the questionnaire. Questionnaire
      validity and reliability were evaluated in a small pilot study and in a larger
      cross-sectional study of 3000 individuals. Analyses included tests for
      reliability and internal consistency, exploratory and confirmatory factor
      analysis, and tests for discriminative ability and convergent validity. RESULTS:
      The final questionnaire included 25 items on SHS (SHSQ-25), and encompassed 5
      subscales: fatigue, the cardiovascular system, the digestive tract, the immune
      system, and mental status. Overall, 2799 of 3000 participants completed the
      questionnaire (93.3%). Test-retest reliability coefficients of individual items
      ranged from 0.89 to 0.98. Item-subscale correlations ranged from 0.51 to 0.72,
      and Cronbach's alpha was 0.70 or higher for all subscales. Factor analysis
      established 5 distinct domains, as conceptualized in our model. One-way ANOVA
      showed statistically significant differences in scale scores between 3 occupation
      groups; these included total scores and subscores (P<0.01). The correlation
      between the SHS scores and experienced stress was statistically significant
      (r=0.57, P<0.001). CONCLUSIONS: The SHSQ-25 is a reliable and valid instrument
      for measuring sub-health status in urban Chinese.

PMID- 19749498
TI  - Factors associated with psychological distress in a community-dwelling Japanese
      population: the Ohsaki Cohort 2006 Study.
AB  - BACKGROUND: In Asia, there has been no population-based epidemiological study
      using the K6, a 6-item instrument that assesses nonspecific psychological
      distress. METHODS: Using cross-sectional data from 2006, we studied 43,716
      (20,168 men and 23,548 women) community-dwelling people aged 40 years or older
      living in Japan. We examined the association between psychological distress and
      demographic, medical, lifestyle, and social factors by using the K6, with
      psychological distress defined as 13 or more points out of a total of 24 points.
      RESULTS: The following variables were significantly associated with psychological
      distress among the population: female sex, young and old age, a history of
      serious disease (hypertension, diabetes mellitus, stroke, myocardial infarction,
      or cancer), current smoking, former alcohol drinking, low body mass index,
      shorter daily walking time, lack of social support (4 of 5 components), and lack
      of participation in community activities (4 of 5 components). Among men aged 40
      to 64 years, only "lack of social support for consultation when in trouble" and a
      history of diabetes mellitus remained significant on multivariate analysis. Among
      men aged 65 years or older, age was not significantly associated with
      psychological distress, and the significant association with current smoking
      disappeared on multivariate analysis. Among women aged 40 to 64 years, a history
      of stroke was not associated with psychological distress. Among women aged 65
      years or older, the significant association with current smoking disappeared on
      multivariate analysis. CONCLUSIONS: A number of factors were significantly
      associated with psychological distress, as assessed by the K6. These factors
      differed between men and women, and also between middle-aged and elderly people.

PMID- 19749499
TI  - Diurnal temperature range is a risk factor for coronary heart disease death.
AB  - BACKGROUND: Although the relation between day-to-day temperature change and
      coronary heart disease (CHD) mortality is well established, it is unknown whether
      temperature variation within 1 day, ie, diurnal temperature range (DTR), is an
      independent risk factor for acute CHD death. METHODS: We used time-series and
      case-crossover approaches to assess the relation between DTR and daily CHD
      mortality between 2001 and 2004 in Shanghai, China. Specifically, we used
      exposures averaged over periods varying from 1 to 5 days to assess the effects of
      DTR on CHD mortality. We estimated the percent increase in the number of daily
      deaths related to CHD that were associated with DTR, after adjustment for daily
      meteorologic conditions (temperature and relative humidity) and levels of outdoor
      air pollutants. RESULTS: Both time-series and case-crossover analyses showed that
      DTR was significantly associated with the number of daily deaths related to CHD.
      A 1 degrees C increase in 2-day lagged DTR corresponded to a 2.46% (95% CI, 1.76%
      to 3.16%) increase in CHD mortality on time-series analysis, a 3.21% (95% CI,
      2.23% to 4.19%) increase on unidirectional case-crossover analysis, and a 2.13%
      (95% CI, 1.04% to 3.22%) increase on bidirectional case-crossover analysis.
      CONCLUSIONS: Our findings suggest that DTR is an independent risk factor for
      acute CHD death.

PMID- 19749506
TI  - Gastrointestinal bleeding because of hookworm infection diagnosed by capsule
      endoscopy.

PMID- 19749507
TI  - Signature genes for both hepatoblastoma and hepatocellular carcinoma.

PMID- 19749508
TI  - Anti-Helicobacter pylori antibody responses specific for VacA do not trigger
      primary biliary cirrhosis-specific antimitochondrial antibodies.

PMID- 19749509
TI  - Will skepticism stop the evolution of endoscopic GERD treatment?

PMID- 19749585
TI  - Publishing studies that involve "off-label" use of drugs: formalizing Regional
      Anesthesia and Pain Medicine's policy.

PMID- 19749586
TI  - Meningeal (postdural) puncture headache, unintentional dural puncture, and the
      epidural blood patch: a national survey of United States practice.
AB  - BACKGROUND: Meningeal (postdural) puncture headache (MPH) is a familiar
      iatrogenic complication. The optimal means of prevention, management, and
      treatment of this disorder are uncertain. The purpose of this study was to
      determine current practice among United States (USA) anesthesiologists regarding
      MPH as well as the related issues of unintentional dural puncture (UDP), the
      epidural blood patch (EBP), and proposed alternatives to the EBP. METHODS: A
      survey form was sent as a single mailing to each practicing USA member of the
      American Society of Regional Anesthesia and Pain Medicine in June 2006. RESULTS:
      Data were analyzed from 1024 returned survey forms (29.4% response rate). Major
      findings were as follows: Written institutional protocols for managing UDP and
      MPH are uncommon. The preferred method of immediately dealing with an UDP when
      providing analgesia for labor is to reattempt the epidural at another level
      (73.4%). When intrathecal catheters are used for labor analgesia, they are most
      often removed immediately after delivery (56.5%). After UDP in the obstetric
      setting, aggressive hydration and encouraging bed rest are the most frequently
      used prophylactic measures against the development of MPH. Frequently used
      treatment options for MPH include aggressive hydration, the EBP, oral caffeine,
      oral nonopioid analgesics, and bed rest. With the exception of a uniform blood
      volume (16-20 mL), procedural details of the EBP vary considerably among
      practitioners. The use of materials other than blood for epidural patch is
      uncommon. CONCLUSIONS: Various measures, many poorly supported by the literature,
      are used prophylactically after UDP and in the treatment of MPH. Despite being
      nearly universally used as treatment of MPH, the EBP procedure itself remains
      largely nonstandardized.

PMID- 19749587
TI  - Highlights of Regional Anesthesia and Pain Medicine's 2009-2010 information for
      authors.

PMID- 19749590
TI  - Does fascia iliaca block result in obturator block?

PMID- 19749591
TI  - Dextrose 5% in water as an alternative medium to gel for performing ultrasound
      guided peripheral nerve blocks.

PMID- 19749592
TI  - Interscalene brachial plexus block-anatomic considerations.

PMID- 19749593
TI  - Color Doppler as a surrogate marker of needle-tip location in ultrasound-guided
      regional anesthesia.

PMID- 19749594
TI  - Needle visualization in ultrasound-guided regional anesthesia: technological
      challenges and educational solutions.

PMID- 19749595
TI  - Multimodal analgesia after total joint arthroplasty.

PMID- 19749596
TI  - Identification of the epidural space using pressure measurement with the compuflo
      injection pump--a pilot study.

PMID- 19749597
TI  - Ultrasound-guided infraclavicular nerve block and the cephalic vein.

PMID- 19749598
TI  - Normal magnetic resonance appearance after epidural catheter insertion.

PMID- 19749599
TI  - No hard evidence on ultrasound-guided versus conventional regional anesthesia.

PMID- 19749601
TI  - Workers' compensation costs among construction workers: a robust regression
      analysis.
AB  - BACKGROUND: Workers' compensation data are an important source for evaluating
      costs associated with construction injuries. METHODS: We describe the
      characteristics of injured construction workers filing claims in Illinois between
      2000 and 2005 and the factors associated with compensation costs using a robust
      regression model. RESULTS: In the final multivariable model, the cumulative
      percent temporary and permanent disability-measures of severity of injury
      explained 38.7% of the variance of cost. Attorney costs explained only 0.3% of
      the variance of the dependent variable. DISCUSSION: The model used in this study
      clearly indicated that percent disability was the most important determinant of
      cost, although the method and uniformity of percent impairment allocation could
      be better elucidated. There is a need to integrate analytical methods that are
      suitable for skewed data when analyzing claim costs.

PMID- 19749602
TI  - Monitoring worksite clinic performance using a cost-benefit tool.
AB  - OBJECTIVE: The purpose of this study was to explore the usefulness of
      continuously assessing the return on investment (ROI) of worksite medical clinics
      as a means of evaluating clinic performance. METHODS: Visit data from January 1,
      2007, to December 31, 2008, were collected from all the on-site clinics operated
      for the Pepsi Bottling Group. An average system-wide ROI was calculated from the
      time of each clinic's opening and throughout the study period. A multivariate
      linear regression model was used to determine the association of average ROI with
      penetration/utilization rate and plant size. RESULTS: A total of 26 on-site
      clinics were actively running as of December 2008. The average ROI at the time of
      start up was 0.4, which increased to 1.2 at approximately 4 months and 1.6 at the
      end of the first year of operation. Overall, it seems that the cost of operating
      a clinic becomes equal to the cost of similar care purchased in the community
      (ROI = 1) at approximately 3 months after a clinic's opening and flattens out at
      the end of the first year. The magnitude of the ROI was closely related to the
      number of visits (a function of the penetration/utilization rate) and the size of
      the plant population served. CONCLUSION: Serial monitoring of ROIs is a useful
      metric in assessing on-site clinic performance and quantifying the effect of new
      initiatives aimed at increasing a clinic's cost effectiveness.

PMID- 19749603
TI  - Who is paying the bills? Health care costs for musculoskeletal back disorders,
      Washington State Union Carpenters, 1989-2003.
AB  - OBJECTIVE: Factors associated with private health insurance payment rates for
      musculoskeletal back disorders were examined among a 15-year cohort of union
      carpenters. Payment patterns were contrasted with work-related back injury rates
      over time. METHODS: Negative binomial regression was used to assess payment
      rates; generalized estimated equations accounted for multiple observations per
      person and cost correlation within subjects. RESULTS: Payment rates increased
      after work-related injury and with the number of injuries. Increasing private
      payments and deductibles (inflation-adjusted and discounted) were observed in
      contrast with a marked decline in reported work-related injuries. CONCLUSIONS:
      Private insurance payments do not appear to be independent of work-related back
      injury. Findings suggest cost-shifting from workers' compensation to the union
      provided health insurance and to the worker; they also provide a warning
      regarding reliance on workers' compensation statistics for surveillance of work
      related disorders or disease.

PMID- 19749604
TI  - Risk of mesothelioma and occupational exposure to asbestos and man-made vitreous
      fibers: evidence from two case-control studies in Montreal, Canada.
AB  - OBJECTIVE: To examine the effects of exposure to occupational asbestos and man
      made vitreous fibers (MMVF) across a wide range of occupations on risk of
      mesothelioma. METHODOLOGY: Two population-based case-control studies (1979-1986
      and 1996-2001) provided 35 histologically confirmed mesothelioma cases and 1965
      controls. A detailed job history was obtained to evaluate occupational exposure
      to many agents, including asbestos and MMVF. RESULTS: The mesothelioma odds ratio
      for exposure to any asbestos type was 3.7 (95% confidence interval = 1.7 to 7.8).
      The subset exposed to amphibole fibers experienced an odds ratio = 7.0 (95%
      confidence interval = 2.7 to 18.5). Effects of MMVF could not be disentangled
      from those of asbestos. DISCUSSION: In workers with exposure levels lower than in
      most historical cohort studies and across a wide range of industries, a strong
      association was found between asbestos, especially when it was amphibole, and
      mesothelioma.

PMID- 19749605
TI  - Association of age with muscle size and strength before and after short-term
      resistance training in young adults.
AB  - The purpose of this study was to assess the association of age with muscle mass
      and strength in a group of young adults before and after 12 weeks of progressive
      resistance training. Eight hundred twenty-six young males and females (age 24.34
      +/- 5.69 yr, range 18-39 yr) completed a strictly supervised 12-week unilateral
      resistance training program of the nondominant arm. Isometric (maximal voluntary
      contraction [MVC]) and dynamic strength (1 repetition maximum [1RM]) of the elbow
      flexors and cross-sectional area (CSA) of the biceps-brachii using magnetic
      resonance imaging (MRI) scans were measured before and after training. Pearson
      correlation coefficients were calculated for size and strength variables and age.
      In addition, the cohort was divided into groups according to decade of life and
      differences assessed by analysis of variance. Age correlated significantly and
      positively with all pretraining measures of muscle size and strength (CSA: r =
      0.191, p < 0.001; MVC: r = 0.109, p = 0.002; 1RM: r = 0.109, p = 0.002). Age was
      not related to the training-induced changes in CSA or MVC but was negatively
      associated with the change in 1RM (r = -0.217, p < 0.001). The study indicates
      that age does have a significant positive relationship with muscle size and
      strength in untrained young adults. Although age was negatively associated with
      improvements in 1RM, the effect of age was small relative to the improvements
      induced through resistance training, thus suggesting age does not limit response
      to training in any practical way during early adulthood.

PMID- 19749606
TI  - NO contributes to abnormal vascular calcium regulation and reactivity induced by
      peritonitis-associated septic shock in rats.
AB  - Calcium plays an important role in determining vascular smooth muscle tone.
      Norepinephrine (NE)-induced vascular contraction contains two components: 1) Ca2+
      release from the sarcoplasmic reticulum as the fast phase and 2) Ca2+ influx via
      a voltage-dependent calcium channel as the slow phase. This study used functional
      isometric tension recording to evaluate mediators contributing to abnormal NE
      induced Ca2+ handling and reactivity in isolated thoracic aortas from septic
      rats. Sepsis was induced by cecal ligation and puncture (CLP), and thoracic
      aortas were removed at 18 h after CLP. Our results showed that rats that received
      CLP for 18 h manifested severe hypotension and vascular hyporeactivity to NE in
      vivo. This vascular hyporeactivity to NE was also observed in the aorta obtained
      from CLP-induced sepsis rat. Both the fast and slow phases of NE-induced
      contraction were reduced in aortas from sepsis rats. To clarify what possible
      mediators contribute to the abnormal Ca2+ handling in aortas from sepsis animals,
      inhibitors of Ca2+ channel and release were used. Inhibition by 2-aminoethoxy
      diphenyl borane, ryanodine, and cyclopiazonic acid of the NE-induced contraction
      in Ca2+-free solution was greater in the aorta from sepsis rats and inhibitions
      of cyclopiazonic acid and ryanodine, but not of 2-aminoethoxy-diphenyl borane,
      were attenuated by NOS inhibitor N[omega]-nitro-l-arginine methyl ester. In
      addition, the attenuation of NE-induced contraction by nifedipine in the aorta
      was also greater in the CLP group. Our results suggest that abnormal NE-induced
      Ca2+ handling associated with vascular hyporeactivity in the CLP-induced sepsis
      is caused by a major decrease in sarcoplasmic reticulum function and a minor
      impairment of voltage-dependent Ca2+ channels on membrane to Ca2+ handling, at
      least, in the aorta, and this could be attributed to an overproduction of NO in
      sepsis.

PMID- 19749607
TI  - The spectrum of findings in cases of sudden death due to blunt cardiac trauma-
      'commotio cordis'.
AB  - Commotio cordis is a term used for cases of sudden cardiac death due to
      nonpenetrating chest trauma without evidence of underlying myocardial disease or
      injury. Contusio cordis has been reserved for cases of chest trauma where there
      is cardiac bruising. Three deaths due to blunt cardiac and chest trauma after
      vehicle accidents are presented where the only significant injuries were
      contusions of the heart and fractures of the sternum and ribs. One case had
      moderate coronary artery atherosclerosis and another had a blood alcohol level of
      0.218%. Given that individuals with cardiac bruising, chest trauma, coronary
      atherosclerosis, and alcohol intoxication may still die of the same mechanisms as
      in classic commotio cordis, and that these entities represent a spectrum of
      findings after chest impact, it may be more useful to separate cases into related
      subcategories: (A) those with no evidence of injury or underlying cardiovascular
      disease, (B) those with chest wall fractures, chest wall contusions and/or
      cardiac contusions, and (C) those with underlying cardiovascular disease or the
      presence of substances such as alcohol or drugs that may reduce the threshold for
      cardiac arrhythmias. As there may be cases with a number of these factors, a
      fourth category (D) includes those with a combination of injuries and
      predisposing factors (ie, categories B and C). Including cases such as these
      under the diagnostic umbrella of commotio cordis may demonstrate that a wider
      range of individuals are at risk for death from blunt cardiac trauma than sports
      playing adolescents.

PMID- 19749608
TI  - Tameshi-giri, or Japanese sword test-cutting: a historic overview.
AB  - The martial Japanese history is characterized by the development of a particular
      samurai sword known as the katana. It was believed that this sword was the
      reflection of the warrior's soul, and thus it had to be tested to estimate its
      sharpness, efficiency, and cutting ability. A variety of cutting tests was done
      on animals and bamboos, but some were also carried out on human beings. This
      technique was called tameshi-giri. Although the practice on human beings has
      since disappeared, the remaining cutting test records represent precious
      information about human body's resistance to sharp weapons.

PMID- 19749609
TI  - Combined pathological effects of cocaine abuse and HIV infection on the
      cardiovascular system: an autopsy study of 187 cases from the Fulton County
      Medical Examiner's office.
AB  - This autopsy study evaluates the possible cumulative effects of cocaine use in
      HIV-infected adult individuals on cardiovascular tissue. A total of 187 autopsy
      case reports and available H&E sections of myocardium and coronary arteries were
      reviewed. Four major study groups were defined: (A) a total of 63 cases positive
      for cocaine and negative for HIV (COC); (B) 40 cases positive for HIV/AIDS and
      negative for cocaine (HIV), (C) 23 cases both HIV/AIDS and cocaine (HIV/COC), and
      (D) a control group of 61 age-, sex- and race-matched, negative for cocaine and
      for HIV (CONT). The following morphologic and demographic data were analyzed:
      heart weight, left ventricular hypertrophy, myocardial fibrosis, thickening of
      the intramyocardial vessels, myocarditis, acute or remote myocardial infarcts
      (MI), age, sex, and race. Increased frequency of coronary wall and adventitial
      infiltrates, myocarditis, and thickened intramyocardial vessels present in
      HIV/COC group (14.5%, 17.4%, and 17.4% vs. 6.5%, 3.3%, and 0% in CONT group) may
      indicate possible combined and/or cumulative effects of HIV and cocaine on
      cardiovascular pathology.

PMID- 19749610
TI  - Asphyxia: a rare cause of death for motor vehicle crash occupants.
AB  - Motor vehicle related trauma is one of the leading causes of traumatic death.
      Although most of these deaths are because of severe blunt force trauma, there are
      people without severe injury who die of asphyxia related to the motor vehicle
      collision. There were 37 deaths because of motor vehicle related asphyxia in San
      Diego County during 1995-2004. Almost half (48.6%) of these deaths were because
      of compression asphyxia, 29.7% were positional asphyxia deaths, and 16.2% died of
      a combination of compression and positional asphyxia. We were unable to classify
      the mechanism of asphyxia for the remaining 5.4% of asphyxia deaths. Almost all
      occupants dying from asphyxia were involved in rollover crashes and may have been
      incapacitated by obesity, drug or alcohol intoxication, or blunt force trauma.
      Compression asphyxia deaths occurred both from vehicle crush with intrusion into
      the passenger compartment and from ejection of the occupant and subsequent
      crushing by the vehicle. Positional asphyxia occurred in positions interfering
      with normal respiration, including inversion. None of the occupants had injury
      severe enough to result in death at the scene if they had not first died of
      asphyxia. This study suggests classifying the mechanism of asphyxia for these
      fatalities may be a challenge to forensic pathologists who seldom see these rare
      deaths.

PMID- 19749611
TI  - Suicide and ethnicity in Malaysia.
AB  - This article highlights methods of ending life in different ethnic groups. This
      inference is drawn from analysis of data from suicidal cases from the University
      Malaya Medical Centre mortuary. This study also looked at sex, age, social, and
      employment factors. Kuala Lumpur has sizeable populations of Muslims, Chinese,
      Indians and Indonesian, etc. This study is based on 251 cases of suicide that
      were reported at the University Malaya Medical Centre from 2000 to 2004. Malaysia
      has a population of 22,662,365 people with 3 major ethnic groups: Malay (58%),
      Chinese (24%), and Indians (8%) with a minority of "others" (10%), which includes
      foreigners, Sabahan, and Sarawakian. This research found suicides of 164 male
      (65%) and 87 female (35%) victims. Their age ranged from 15 to 80 years. The age
      group from 21 to 30 had the highest total cases of suicide (83 of 251; 33.1%).
      Among ethnic groups highest rate of suicide was among Chinese with a total of 120
      cases (120 of 251; 47.8%). As far as lone method of suicide is concerned,
      hangings accounted for the highest proportion of cases (108 of 251; 43%). Among
      ethnic groups, jumping from height was the commonest method used by Chinese (49
      of 120; 41%), Malay (9 of 16; 56%), and others (15 of 28; 53.4%); whereas,
      hanging was the commonest method of committing suicide by Indians (49 of 87);
      Muslims showed the lowest cases of suicide (18 of 251; 7.2%). In poisoning group
      Indian was the highest ethnic group who used this method (20 of 37; 54.1%).

PMID- 19749612
TI  - Analysis of cervical injuries in persons with head injuries.
AB  - To determine which clinical factors are useful for predicting concomitant
      injuries of the cervical spine and cervical spinal cord in persons with head
      injuries, we examined the nature and mechanisms of cervical injuries. For 109
      forensic autopsies of persons with head injuries, the cause of injury, mechanism
      of cervical injury, survival time, and anatomic injury severity (1990 revision of
      the abbreviated injury scale [AIS] and injury severity score) were determined.
      Traffic accidents were the most common cause of injuries (41.3%), followed by
      slips and falls (24.8%), assaults (17.4%), and falls from height (9.2%). The mean
      maximum AIS scores and the AIS scores of the head or neck were similar in the 4
      groups. Cervical spine injuries and epidural or subdural hemorrhages of the
      cervical spinal cord were more common in persons dying in traffic accidents and
      falls from height than in persons dying in slips and falls or assaults. Cervical
      injuries were significantly more common in persons sustaining frontal impacts
      than lateral or rear impacts. The most common cervical hyperextension injuries
      were atlanto-occipital and atlantoaxial dislocation and injuries of the 5th
      intervertebral disc. Our results suggest that persons with injuries of the head
      due to high-energy frontal impacts should be carefully examined for concomitant
      cervical injuries. These findings should be helpful for decreasing preventable
      deaths from undiagnosed cervical injuries in head-injured persons.

PMID- 19749613
TI  - Sauna deaths in Sweden, 1992-2003.
AB  - Deaths from 1992 through 2003 related to sauna bathing in Sweden were collected
      from a national computer data base comprising all medicolegal autopsies,
      generating 77 cases included in this study. Of all deaths, 82% were men, most of
      them middle-aged. The geographic distribution seemed to be roughly related to the
      population density. Most bathers died on a weekend, and 84% were found dead in a
      sauna. In 69 cases, the blood alcohol concentration was determined; 49 (71%) of
      these tested positive, often with high concentrations. In 65 cases, a major
      disease/state that could explain death was identified; 34 (44%) of these deaths
      were related to alcohol and 18 (23%) cardiovascular. Other causes of death were
      drowning, CO poisoning, O2 deprivation, amphetamine intoxication, and burn
      injuries. In 13 cases, the cause of death remained undetermined. The results
      indicate that sauna habits in Sweden are similar to those in Finland but probably
      less common. The most important risk group is middle-aged men, especially those
      with heavy alcohol consumption. Among the cases found dead in a sauna, all but 2
      were found alone. Obviously, bathing alone is a risk factor that can easily be
      avoided and should perhaps be emphasized more.

PMID- 19749614
TI  - Russian roulette and risk-taking behavior: a medical examiner study.
AB  - Fatal Russian roulette refers to death following an act of extreme bravado in
      which the individual spins the cylinder of a revolver loaded with at least one
      cartridge, aims the muzzle at the head, and pulls the trigger. The majority of
      victims are men younger than 30 years who, in the presence of others, are under
      the influence of ethanol or other drugs. This is a 10-year (1993-2002)
      retrospective review of self-inflicted gunshot wounds of the head, among which we
      culled and paid special attention to cases of Russian roulette, at the Medical
      Examiners' Offices in Kentucky. Of the 24 incidents of Russian roulette, the
      majority of victims were white (79.2%), and all were men between 14 and 47 years
      with a mean age of 24.8 years. Compared with other cephalic firearm suicides, the
      subjects engaging in Russian roulette were significantly more likely to have
      elevated blood levels (> or = 0.1%) of ethanol along with various drugs detected
      in urine. Although the presumed intent of the risky act is to survive, Russian
      roulette is deemed to be suicide, which is based on a comprehensive understanding
      of the inherently deliberate, volitional actions of the decedent.

PMID- 19749615
TI  - Analysis of discrepancies between external body examination and forensic autopsy.
AB  - At present in France, most of the medico-legal investigations are restricted to
      death scene investigation, which means there is only an external body examination
      without subsequent autopsy. The aim of our study was to show the limits of death
      scene investigation by establishing the rate of discrepancies between the results
      of external body examination and forensic autopsy.A retrospective study was
      carried out on 200 autopsy cases which were all preceded by death scene
      investigation and performed in 2002. For each case, age, sex, body weight, body
      state, place, and time of death were reported. The number of recent trauma
      lesions detectable at external body examination and at autopsy was studied.
      Conclusions about manner and cause of death between death scene investigation and
      autopsy were also studied. Discrepancy rate about interpretation of the lesions
      seen at external body examination and at autopsy was determined. Discrepancy
      between minor external trauma lesions and severe internal trauma lesions was also
      studied.The mean age of the studied population was 42.4 years. Sex ratio was 2.2.
      External body examination was limited by body state in 32% of the cases. The mean
      number of recent external trauma lesions recorded at autopsy was significantly
      higher than those recorded during death scene investigation. Manner and causes of
      death were undetermined after death scene investigation in 54.5% and 49% of the
      cases, respectively. When the cases were determined by death scene investigation,
      discrepancy rate, respectively, was 5% and 9% of all cases (n = 200) for manner
      and causes of death.Death scene investigation even carried out by a well-trained
      forensic physician is not reliable relative to cause and manner of death. Our
      study underlines the necessity in the future to perform more forensic autopsies
      in France, relying on the European harmonization of medico-legal autopsy rules.

PMID- 19749616
TI  - Mortality by homicide in homosexuals: characterization of the cases registered in
      Mexico between 1995 and 2000.
AB  - This work shows a first approximation to the magnitude and characteristics of
      mortality by homicide in homosexuals in Mexico using the cases registered between
      the years 1995 and 2000. A statistical analysis was performed of the homicides
      against homosexuals that were registered through the review of newspaper articles
      published by the National Press. Sex, age of the victims, kind and number of
      weapons used, wounds endured, and the situation in which the corpses found were
      registered. The greater mortality by homicide due to homosexual orientation was
      recorded in men (95%); it was found that the cases accumulated in the cohort of
      the third and fourth decades of their age (43%). The homicides were characterized
      by extreme violence which included the use of various arm types (33%) and wounds
      (32%). The most frequent situations that occurred were finding the corpses naked
      and tied (13%). The features of the homicide against homosexuals are associated
      to the general attributes of the predominant masculinity model; therefore, at a
      macro social level, some reasons are found in the social construction of
      homophobia. The degree of violence in these crimes adduces the consideration that
      they are hate crimes.

PMID- 19749617
TI  - The analysis of hormones and enzymes extracted from endocrine glands of the neck
      region in deaths due to hanging.
AB  - Our study was designed to determine whether the hormone and enzyme levels that we
      have mentioned in serum specimens can be used in postmortem examinations of the
      cases of hanging or not. Our research includes the postmortem results of the
      thyroid tissue pathologic examinations, serum levels of triiodothyronine (fT3),
      thyroxine (fT4), thyrotropin (TSH), thyroglobulin, parathormone (PTH),
      calcitonin, and amylase in cases of death due to hanging. The mean of fT3 and
      thyroglobulin levels were higher in hanging cases than those of sudden death
      cases. This difference was statistically significant (P < 0.05). In our study, we
      obtained data demonstrating that high postmortem levels of free T3 and
      thyroglobulin may be indicators of vital reaction in hanging cases. In such cases
      of death, it seems that applying pressure on the neck region where the thyroid
      gland is located causes the leakage of thyroglobulin as well as fT3, the active
      form of the thyroid hormone.

PMID- 19749618
TI  - Morphologic analysis of third-molar maturity by digital orthopantomographic
      assessment.
AB  - Accurate timing of the eruption of first and permanent teeth is an important
      parameter in forensic odontology to establish the age of dead or live
      individuals. Determination of adulthood may determine, for example, whether an
      individual convicted of a crime is sentenced as an adult and incarcerated in a
      state penal institution or as a juvenile and sent to a juvenile camp. At present,
      there is a large immigrant population in Italy, and young foreign criminals
      sometimes have false passports bearing a later birth date, with the aim of
      evading punishment. In such circumstances, age determination is becoming a
      significant forensic issue.Late in adolescence, after formation of the premolars
      and canines, only the third molars continue to develop. According to several
      studies, although the third molars are the most variable teeth in the dentition,
      they remain the most reliable biologic indicator available for estimation of age
      during the middle teens and early twenties.In this study, the authors test the
      possibilities offered by orthopantomography executed by means of digital
      technology, with the aim of exploiting the advantages of the computerized digital
      technique compared with the conventional technique, to determine adult age on the
      basis of root development of the third molar.Digital radiography is simple to
      use, quick, and effective, allowing superimposition and enlargement; the images
      can be electronically stored and transported. In comparison with traditional
      orthopantomography, the digital technique features greater diagnostic accuracy of
      some anatomic structures: upper and lower front teeth, root apexes, floor of the
      nasal fossa and maxillary sinus, nasal septum, mandibular condylus. Moreover,
      digital orthopantomography suffers less from artifacts.The digital
      orthopantomographies of 83 Caucasian subjects (43 females and 40 males) aged
      between 16 and 22 years were analyzed in standard conditions, assessing the
      degree of maturation of the upper and lower third molars. A standardized computer
      procedure was used to acquire the x-ray images, recording 3 per plate: the
      overall orthopantomography and 2 enlargements of optical type of the left and
      right sides, to reveal the third molars while maintaining unaltered the image
      resolution.For the analysis, the authors adopted Demirjian's staging system that
      classifies development of the third molar in 8 stages (A, B, C, D, E, F, G, H) on
      the basis of morphologic criteria. This has been statistically proved to feature
      notable precision and high predictive ability.To assess any sex-related
      variations in mineralization speed, the series was subdivided by gender. The
      study demonstrated that such differences are more evident under the age of 18
      years.Overall, the observation of 245 third molars showed faster development of
      the upper than the lower third molars, a prevalence of stages D to G in the age
      range between 16 and 18 years, and a clear predominance of stage H in individuals
      over 18 years of age. Finally, an intermediate stage between G and H was
      demonstrated in subjects aged between 17 and 21 years.

PMID- 19749619
TI  - Fatal anaphylaxis to indoor native fire ant stings in an infant.
AB  - The red (Solenopsis invicta) and black (Solenopsis richteri) imported fire ants
      (IFA) are a common cause of venom allergy in the southeastern United States.
      Hypersensitivity to stings of native fire ants is less common, although
      anaphylaxis has been reported to various native Solenopsis species. There have
      been numerous reports of indoor stings caused by IFA, including in nursing homes
      and private residences. The following is a report of fatal anaphylaxis to a
      native fire ant sting in an infant that occurred indoors at a daycare facility. A
      3-month-old female was left unattended on a bed. The caregiver had heard the
      child crying, but attributed this to colic. A short time later, the caregiver
      found the child apneic and covered with ants. Emergency medical services were
      summoned, and resuscitation attempts were unsuccessful. Postmortem examination
      revealed approximately 40 erythematous lesions without pustules. Examination of
      the respiratory system was notable for congested parenchyma and mild laryngeal
      edema. Laboratory studies revealed an elevated tryptase of 23.9 ng/mL and
      radioallergosorbent test (RAST) of 1.4% specific IgE antibody binding to
      Solenopsis richteri venom. RAST for specific IgE antibody binding to Solenopsis
      invicta venom was negative. Ants recovered from the scene were identified by an
      entomologist as Solenopsis xyloni, a native fire ant endemic to the southwestern
      United States. Native fire ants have features that distinguish them from IFA.
      Some native species do not build mounds, and stings may not result in pustules
      characteristic of IFA. There is significant cross-reactivity among the venoms of
      Solenopsis species, although some species' specificity exists for the Sol 2
      allergen. Testing and treatment with IFA whole-body extract is likely to be to be
      effective for native fire ant allergy. A mixture of S. invicta and S. richteri
      extracts should be considered when native fire ant species are presumed to cause
      the primary sensitization to reduce the chance that species-specific reactivity
      is missed.

PMID- 19749620
TI  - Accidental death in autoerotic maneuvers.
AB  - The authors from the Florence Forensic Department present a case that
      demonstrates the paradigms attached to accidental deaths while performing
      autoerotic maneuvers. The incidents of such practices are underestimated and are
      only the tip of the iceberg since they do not represent the cases that are never
      reported due to successful practice. After analyzing the statistic data, the
      authors describe the case and discuss about the element that prove the accidental
      nature of the death and the importance of the correct application of forensic
      methodology at the scene and in the mortuary.

PMID- 19749621
TI  - The identification of submerged skeletonized remains.
AB  - Examination was undertaken of skeletonized remains contained within 2 rubber
      boots dredged by a fishing boat from a depth of 145 m, approximately 185 km off
      the southern Australian coast in the Great Australian Bight. The boots had been
      manufactured in Australia in July 1993 and were of a type commonly used by local
      fishermen. Examination of the lower legs and feet revealed well-preserved bones
      with arthritic changes in keeping with an older male. DNA analyses using
      reference samples taken from relatives of fishermen who had disappeared in the
      area resulted in the identification of the victim as a 52-year-old prawn
      fisherman who had been swept off a boat over a decade earlier. DNA stability had
      been maintained by the low light, cold temperatures, and alkaline pH of the ocean
      floor. Integration of pathologic, anthropologic, and biologic analyses with
      police investigations enabled a positive identification to be made despite the
      unusual nature of the location of the remains and the time lapse since the
      disappearance of the victim.

PMID- 19749622
TI  - A medieval murder.
AB  - On rare occasion, the body or skeleton of a murder victim may be discovered
      hundreds of years, or even millennia, after the crime. The murder of the 5000
      year-old Stone Age man, found frozen in the ice of the Italian Alps, being the
      most recent example. In most of these cases too much time has passed to allow the
      application of modern forensic technology. We describe here a homicide that
      occurred between 1310 and 1390. The victim died of a crossbow injury, with a bolt
      passing between the 2nd and 3rd vertebrae, completely transecting the brainstem.
      The crossbow was, for more than 2 and one half centuries (1200-1460), the weapon
      of choice in European armies, and its use would not have been unusual. The choice
      of weapon, and other features of the crime, makes it possible to arrive at some
      reasonable conclusions about the circumstances of the death.

PMID- 19749623
TI  - Death due to late-presenting congenital diaphragmatic hernia in a 2-year-old
      child.
AB  - Congenital diaphragmatic hernia (CDH) is classically regarded as a neonatal
      defect presenting with respiratory distress; however, not all CDH will present in
      this manner. Unlike newborn deaths related to CDH, where the mechanism of death
      is respiratory in nature, the mechanism of death in late-presenting CDH is not
      always due to respiratory compromise. In this case report, we present a death
      occurring in a 2 1/2-year-old child who presented to the emergency department
      with complaints of abdominal pain and emesis, and then rapidly decompensated and
      died. Autopsy revealed a CDH, with herniation of abdominal contents into the left
      thoracic cavity, with associated gastric volvulus, necrosis, and rupture.

PMID- 19749624
TI  - Suicide in the bath using weight and elevation of feet.
AB  - Suicide by drowning in the bath is rare. Because it implies to drown in a small
      volume of water, adult victims are often under the influence of alcohol and/or
      drugs. More rarely, the use of weights is seen to induce drowning. Here is the
      case of a 62-year-old woman found dead in the bath. Her feet were tied and
      elevated by a rope attached to the shower head and a hammer was taped to her
      forehead. This very unique suicide is reported along with review of the
      literature on suicide in the bath.

PMID- 19749625
TI  - Sudden death of a 17-year-old boy due to suspected Williams syndrome.
AB  - In this article, we present a case of sudden death of a 17-year-old boy, in which
      diagnosis of Williams syndrome was firstly suspected after medicolegal autopsy,
      on the basis of typical macroscopical changes (facial appearance, dental status,
      supravalvular aortic stenosis with mild enlargement of the heart and significant
      thickening of the left ventricular myocardium) as well as heteroanamnestic data
      (slight mental retardation and nervousness). All other causes of sudden death
      were excluded. The definite diagnosis of this syndrome could not be corroborated
      as specific genetic analysis (fluorescent in situ hybridization test) could not
      be performed because of the lack of appropriate technical facilities.

PMID- 19749626
TI  - Heart luxation and myocardium rupture in postmortem multislice computed
      tomography and magnetic resonance imaging.
AB  - Postmortem cross-sectional imaging in situ of nontraumatic human heart and of the
      heart with a penetrating trauma has already been described. In postmortem
      multislice computed tomography (MSCT) and magnetic resonance imaging (MRI) the
      diagnosis of blunt trauma to the heart was reported to be challenging. We
      examined a case of fatal vehicle accident with severe heart trauma, which
      underwent postmortem MSCT and MRI before autopsy. Both radiologic methods showed
      dislocation of the heart. Based on this finding a rupture of the pericardium was
      suspected. T2-weighted MRI sequence and MSCT images allowed for diagnosis of
      myocardium rupture. We conclude that postmortem MSCT and MRI performed in
      suspicion of blunt trauma to the heart in forensic cases are useful documentation
      and diagnostic tools.

PMID- 19749627
TI  - Chronic unreduced anterior shoulder dislocation: application of anatomy to
      forensic identification.
AB  - The uniqueness of anatomic structures and their variations provide the basis for
      forensic identification. During the identification process of 1991-1995 Croatian
      war victims, forensic pathologists and forensic anthropologists were faced with
      the problem of incomplete skeletal remains and insufficient premortem medical
      data. Here we present a case of anterior shoulder dislocation, which was a key
      confirmation in the identification of a war victim. In our case, anterior
      shoulder dislocation was not medically treated for 15 years, and the changes in
      the glenoid cavity and coracoid process indicated morphologic adaptation of
      anatomic structures to the new mechanical and physiological demands.

PMID- 19749628
TI  - Unattended fatal hemorrhage caused by spontaneous rupture of a varicose vein.

PMID- 19749629
TI  - So you want to be ... an otorhinolaryngologist.

PMID- 19749630
TI  - Types of research study: a guide for the foundation year doctor.

PMID- 19749631
TI  - Calcium and phosphate testing.

PMID- 19749632
TI  - Parathyroid surgery.

PMID- 19749633
TI  - The integrated research application system: an introduction.

PMID- 19749634
TI  - How to insert a central line.

PMID- 19749635
TI  - Depression in elderly inpatients: are we doing enough?

PMID- 19749636
TI  - Automatic generic substitution: losing the right medication for the right
      patient.

PMID- 19749638
TI  - Nasal polyps: an update.
AB  - Patients with nasal polyps suffer from a condition that, despite adequate
      treatment, runs a recurrent and remitting course, requiring long-term medication
      and often multiple operations. It is a condition in which the cause remains
      unknown.

PMID- 19749639
TI  - Practical free flap monitoring techniques in head and neck surgery.
AB  - A myriad of techniques varying in complexity and sophistication for monitoring
      flaps have been described but systematic clinical assessment is regarded as the
      most reliable monitoring tool. This article reviews the contemporary clinical
      methods in monitoring free flaps.

PMID- 19749640
TI  - Early vs late tracheostomy in critical care.
AB  - This article reviews the current literature and practice of tracheostomy with
      consideration of timing and the benefits of early tracheostomy, taking account of
      the results from the recent TracMan study.

PMID- 19749641
TI  - 'I'm sorry but you've got cancer': the role of psycho-oncology.
AB  - Patients struggling with cancer undergo significant psychological distress and
      have high rates of psychiatric morbidity. This article considers the
      psychological journey of a cancer patient. It looks at both the short-term and
      the long-term impact of cancer on the psychological health of patients.

PMID- 19749642
TI  - Achilles tendinopathy: pathology and management strategies.
AB  - As patient expectation is rising, surgery is being considered more frequently for
      Achilles tendinopathy. Traditional open interventions have a significant
      morbidity, rising interest in less invasive techniques. This review discusses
      some of the current concepts and controversies in the management and pathology of
      tendinopathy of the Achilles tendon.

PMID- 19749643
TI  - Non-invasive ventilation for acute exacerbations of COPD.
AB  - Acute exacerbations of chronic obstructive pulmonary disease (COPD) causing
      respiratory failure are associated with mortality rates of up to 26%. A new Royal
      College of Physicians guideline aims to impart standards and practical advice to
      those providing a non-invasive ventilation service for these patients. This
      article examines the guideline.

PMID- 19749644
TI  - Managing the appraisal.
AB  - Appraisal is a formal process for doctors at all levels, including doctors in
      training, which supports professional development and stimulates improvements in
      clinical practice. Appraisal skills are fundamental to the process of educational
      supervision.

PMID- 19749645
TI  - An e-mail GP advisory service: a more efficient way of dealing with clinical
      enquiries.
AB  - Good communication between primary and secondary care is vital for patient
      management. This article describes how an e-mail enquiry service for
      endocrinology and diabetes was established within one hospital and the potential
      benefits that it offers.

PMID- 19749646
TI  - Medical schools 100 years ago.

PMID- 19749647
TI  - A neonate with fetal distress and anaemia.

PMID- 19749648
TI  - Ovarian pregnancy: report of three cases and review of the literature.

PMID- 19749649
TI  - Gingival overgrowth secondary to amlodipine.

PMID- 19749650
TI  - Is the ovary a sanctuary for non-Hodgkin's lymphoma? Successful surgical
      management.

PMID- 19749651
TI  - Simple education to drive thromboprophylaxis provision.

PMID- 19749652
TI  - Anatomy dissection: a valuable surgical training tool.

PMID- 19749653
TI  - Should we admit patients with haematological malignancy to intensive care?

PMID- 19749655
TI  - Understanding the role of diet in type 2 diabetes prevention.
AB  - The number of people with type 2 diabetes is increasing at an alarming rate.
      Almost 4% of the UK population currently have diagnosed diabetes. Non-modifiable
      risk factors for diabetes include genetic predisposition, some black and ethnic
      minority groups and increasing age. Type 2 diabetes, (formally known as maturity
      onset diabetes), used to be a condition affecting adults only, although due to
      the increasing levels of obesity, it is now being diagnosed in young people and
      children. A healthy diet and lifestyle can help to prevent or delay the
      development of type 2 diabetes. In particular, strategies to reduce obesity will
      have a beneficial effect on the prevalence of type 2 diabetes, as excess
      adiposity (particularly central adiposity) is a strong risk factor for the
      condition. Dietary measures to reduce the risk of coronary heart disease will
      also help prevent diabetes. Diets low in fat (particularly saturated fat), and
      high in fibre and complex carbohydrates are effective in reducing the risk of
      developing diabetes. Good quality evidence from trials is required to determine
      the role of specific micronutrients in diabetes prevention.

PMID- 19749656
TI  - The role of skin assessment in older people.
AB  - Understanding what to look for, what is normal and what needs to be referred to a
      specialist, gives community nurses confidence in assessing older skin. Skin
      health checks should become a normal part of health surveillance in primary care.
      This article reviews some of the most common changes that occur as skin ages,
      drawing attention to features that indicate possible malignancy as well as
      briefly indicating some common changes due to dry skin and disease processes. The
      principles of sun protection, including some helpful products, and skin treatment
      to aid hydration and maintain health are discussed.

PMID- 19749657
TI  - Understanding the role of smoking in the aetiology of bladder cancer.
AB  - Bladder cancer is common in the UK. Of all the aetiological factors associated
      with the development of the disease, cigarette smoking is the most important, in
      industrialized countries. It is estimated that 60% of all bladder cancers result
      from smoking. The management of bladder cancer is governed by specific
      guidelines. Superficial cancers are managed surgically with transurethral
      resection, while more aggressive tumours are managed with cystectomy (removal of
      the bladder). Additional treatment includes cytotoxic therapy with intravesical
      chemotherapy and immunotherapy agents. However, while treatments may be effective
      in reducing tumour recurrence, the side effects of treatments on the individual's
      quality of life can be devastating. This paper seeks to provide an overview of
      bladder cancer, namely how the disease presents and is subsequently treated. The
      role of smoking is discussed in relation to the development of bladder cancer.
      Also, whether health promotion and education are effective in increasing the
      individual's awareness of the dangers of smoking are explored.

PMID- 19749658
TI  - Supported self care and care planning for patients with long-term conditions.
AB  - Christine Beasley explains the benefits of supported self care for patients with
      long-term conditions, enabling them to make decisions about their care, in
      partnership with their health-care professional. The article also includes a case
      study of the Leeds Community Healthcare team, outlining how nurses implement the
      self care ethos into daily clinical practice.

PMID- 19749659
TI  - Structured patient education: the X-PERT Programme.
AB  - The X-PERT Programme seeks to develop the knowledge, skills and confidence in
      diabetes treatment for health-care professionals and diabetes self-management.
      The programme trains health-care professionals to deliver the six-week structured
      patient education programme to people with diabetes. Over 850 health-care
      professionals have attended the X-PERT 'Train the Trainer' course and audit
      results document improved job satisfaction and competence in diabetes treatment
      and management. National audit statistics for X-PERT implementation to people
      with diabetes illustrate excellent attendance rates, improved diabetes control,
      reduced weight, blood pressure, cholesterol and waist circumference and more
      confidence in self-managing diabetes that has impacted positively on quality of
      life.

PMID- 19749660
TI  - The swine flu, advice giving and the reporting of adverse drug reactions.
AB  - The swine flu pandemic has gripped the headlines over the summer and its
      management in the UK is proving to be controversial. The government's advice to
      issue anti-virals to people of all ages with flu-like symptoms runs contrary to
      World Health Organisation advice. The benefits of anti-virals for children has
      been called into doubt because of the risk of severe side effects. Concern over
      adverse drug reactions has prompted the Medicines and Healthcare products
      regulatory agency to urge health professionals and the public to assist its
      monitoring of the drug by reporting adverse drug reactions. It is essential that
      district nurses have up-to-date knowledge of the adverse reactions of the
      commonly used anti-virals in order to exercise a duty of care to their patients
      by giving appropriate advice and ensuring adequate monitoring and early detection
      of unwanted side effects. This article makes recommendations to district nurses
      for improving patient concordance with prescribed medicines, reporting adverse
      drug reactions via the swine flu ADR portal and how to obtain up-to-date
      information on unwanted side effects.

PMID- 19749661
TI  - Are HIECs the answer?

PMID- 19749662
TI  - Wound care teams: redesigning community nursing services.
AB  - A pioneering community-based multi-disciplinary wound care team, working
      alongside a tissue viability service, developed within East Lancashire teaching
      PCT. The drive to push the nurse-led wound care agenda forward requires powerful
      champions to acknowledge the value of multi-professional care, therefore this
      article embraces a care delivery model based on a 'spend to save' framework. This
      live platform, using a multi-disciplinary specialism, uses an electronic database
      to demonstrate measurable outcomes, reporting weekly and monthly patient and non
      patient activities. The impetus for developing this service was to enable
      community nurses to refocus their time on patients with long-term conditions.

PMID- 19749663
TI  - The lived experience of community nurses treating clients with leg ulcers.
AB  - Chronic leg ulceration impacts negatively on the quality of life of the sufferer
      and has financial implications for the economy. Government health policy aims to
      tackle long-term conditions and restructure services from acute to community
      care. Community nurses play a pivotal role in managing and co-ordinating care to
      leg ulcer patients, yet their personal experience in this clinical situation is
      poorly explored. This qualitative study aims to gain an understanding of
      community nurses' personal experience of treating clients with leg ulcers; this
      is necessary to develop leg ulcer services which are effective, efficient and
      client-centred.

PMID- 19749665
TI  - The use of Silflex in burn wound management.
AB  - This article presents three case studies looking at the effective use of an
      atraumatic wound dressing: Silflex (Advancis Medical). Pain is known to be very
      debilitating in patients with burns and frequent dressing changes can pose a
      painful problem. The case studies, presented here, support the view that Silflex,
      a silicone-based conformable dressing, is a useful adjunct when treating
      superficial burns.

PMID- 19749666
TI  - An interview with Brenda King.

PMID- 19749668
TI  - ROHO Dry floatation technology: implications for clinical practice.
AB  - This article discusses the aetiology of pressure ulcers, the clinical and
      financial cost of pressure ulcer prevention and the need for pressure reducing
      equipment. The role of Dry floatation in pressure ulcer prevention and management
      is explored. How Dry floatation technology works is discussed and its use within
      clinical practice is highlighted. The evidence to support Dry floatation is
      presented.

PMID- 19749669
TI  - Topical antimicrobial agents for the treatment of chronic wounds.
AB  - Chronic wounds are commonly observed in acute and community settings. The
      management of chronic wounds represents a significant proportion of health-care
      resources and makes up a substantial amount of contact time with community-based
      nurses spending approximately 25% to 50% of their time treating wounds. Chronic
      wounds often exhibit increased bacterial burden that can negatively impact upon
      patients, reduce their quality of life and substantially increase treatment costs
      for health care providers. Antibiotic resistance has become a major medical and
      public health problem, and interest has been generated in the use of topical
      therapies to manage wound infection. This article presents an overview of the
      historical use of honey, silver and iodine for the treatment of infected wounds
      progressing through to modern day use and the current evidence base for the use
      of these antimicrobial agents in the management of infected wounds.

PMID- 19749670
TI  - Prenatal nutrition: special considerations.
AB  - Awareness of the importance of nutrition during pregnancy has increased in recent
      years.Pregnancy outcomes vary by prepregnant weight as well as gestational weight
      gain. Inappropriate gain may have both short- and long-term consequences for
      mother and infant. This review article includes the newly released US Institute
      of Medicine prenatal weight gain guidelines, as well as the Dietary Reference
      Intakes for the US and selected European societies.Food safety topics are
      discussed including Listeria, Toxoplasma, peanuts, mercury and other
      contaminants. Preconceptual nutrition is discussed, as are specific at-risk
      prenatal nutrients, including folic acid, choline, vitamin B12, omega-3 fatty
      acids, iodine, calcium, vitamin D, and iron. Current controversies are discussed
      and practical suggestions are given to safely optimize nutrient intake. As part
      of the medical team, a local Registered Dietitian or other nutrition professional
      can give much more detailed guidance and support for a pregnant woman given her
      particular risk factors, including her pre-existing medical conditions and
      cultural concerns, and will emphasize nutritional quality rather than just pounds
      gained.

PMID- 19749671
TI  - Pharmacological use of progesterone and 17-alpha-hydroxyprogesterone caproate in
      the prevention of preterm delivery.
AB  - Preterm delivery (PTD) is defined by the World Health Organization as birth
      before 37 completed weeks of gestation. In Western countries, PTD accounts for
      over 75% of all perinatal morbidity and mortality. The social importance of PTD
      derives from the consideration that it causes near three quarter of neonatal
      deaths not caused by malformations. Progesterone is a steroid hormone which plays
      a crucial role in each step of human pregnancy. Early in pregnancy progesterone
      is produced by the corpus luteum and it is fundamental for pregnancy maintenance
      until placenta takes over this function at 7-9 weeks of gestation. Late in
      pregnancy, the role of progesterone is less clear: certainly, it may be
      importance in maintaining uterine quiescence in the latter half of pregnancy by
      limiting the production of stimulatory prostaglandins and inhibiting the
      expression of contraction-associated protein genes (ion channels, oxytocin and
      prostaglandin receptors, and gap junctions) within the myometrium. In this
      review, the authors included those controlled clinical studies that have used
      either 17 hydroxy progesterone caproate (17P), or progesterone (P) or its
      synthetic derivatives (progestins) in order to avoid or reduce the incidence of
      preterm delivery, in populations of women at increased risk of preterm birth. The
      authors conclude that: 1) the treatment with 17P reduces the incidence of PTD in
      pluriparous women with a previous history of PTD or with recurrent abortion, as
      well as in nulliparous women with an actual risk; 2) the treatment with P reduces
      PTD in nulliparous women, namely in the presence of a silent cervical shortening;
      3) 17P has no efficacy in multiple pregnancy and it is proven not to have adverse
      effects on the infants.

PMID- 19749672
TI  - Intrauterine growth restriction: diagnosis and management. A review.
AB  - Intrauterine growth restriction (IUGR) is the failure to achieve the genetically
      predetermined growth potential and may be caused by maternal, fetal, placental,
      and external factors. IUGR is associated not only with a marked increased risk in
      perinatal mortality and morbidity but also with long-term outcome risks. IUGR is
      clinically suspected when ultrasonographic estimates of fetal size, simmetry or
      weight result abnormal. Exclusion of structural and/or chromosomal anomalies and
      Doppler studies of maternal and fetal circulations is the most effective method
      to differentiate IUGR fetuses secondary to placental dysfunction from those
      secondary to aneuploidy, genetic syndromes, and intrauterine infections. This
      review summarizes the current knowledge about fetal hemodynamics in IUGR
      pregnancies and its relationship with the severity of the disease. A better
      understanding of fetal hemodynamic changes occurring in IUGR will likely lead to
      targeted monitoring intervals in such fetuses leading to an appropriate timing of
      delivery only when fetal risks exceed neonatal risks.

PMID- 19749673
TI  - Defining cerebral palsy: pathogenesis, pathophysiology and new intervention.
AB  - Cerebral palsy (CP) affects 2/1 000 live-born children. There are several
      antenatal factors, including preterm delivery, low birth weight,
      infection/inflammation, multiple gestations, and other pregnancy complications,
      that have been associated with CP in both the preterm and term infant, with birth
      asphyxia playing a minor role. Due to the increasing survival of the very preterm
      and very low birth weight infant secondary to improvements in neonatal and
      obstetric care, the incidence of CP may be increasing. The topics of neonatal
      encephalopathy and CP, as well as hypoxic-ischemic encephalopathy, are of vital
      importance to anyone who ventures to deliver infants. Criteria sufficient to
      define an acute intrapartum hypoxic event as sufficient to cause CP have been
      advanced previously by both the American College of Obstetricians and
      Gynecologists and the International Cerebral Palsy Task Force. This review will
      cover the progression toward defining the pathogenesis and pathophysiology of
      cerebral palsy. Four essential criteria were advanced as prerequisites if one is
      to propose that an intrapartum hypoxic-ischemic insult has caused a moderate to
      severe neonatal encephalopathy that subsequently results in CP. Importantly, all
      four criteria must be met: 1) evidence of metabolic acidosis (pH <7.0 and base
      deficit of 12 mmol/L or more); 2) early onset of severe or moderate neonatal
      encephalopathy in infants born at 34 or more weeks' gestation; 3) CP of the
      spastic quadriplegic or dyskinetic type, and 4) exclusion of other identifiable
      etiologies, such as trauma, coagulation disorders, infectious conditions, or
      genetic disorders. Other criteria that together suggest intrapartum timing are
      also discussed. The focus of this paper is to explore antenatal antecedents as
      etiologies of CP and the impact of obstetric care on the prevention of CP.

PMID- 19749674
TI  - [Reliability of the diagnostic fluid mini-hysteroscopy in the diagnosis of
      intrauterine pathologies].
AB  - AIM: The aim of this study was to determine the diagnostic accuracy of
      minihysteroscopy with fluid distention and vaginoscopic approach for the
      diagnosis of endometrial pathologies. METHODS: This controlled clinical study was
      conducted on 930 women with endometrial abnormalities who referred to our
      Department of Obstetrics and Gynecology, University Medical School of Bari, to
      perform hysterectomy. One week before hysterectomy all the patients underwent
      minihysteroscopy with fluid distention. Histological diagnoses were compared with
      the hysteroscopic findings, and the sensitivity, specificity, positive predictive
      value, negative predictive value, and diagnostic accuracy were determined.
      RESULTS: Hysteroscopy was technically successful in all women and revealed
      sensitivity of 98%, specificity of 99%, a positive predictive value of 92%, a
      negative predictive value of 99%, and diagnostic accuracy of 99% for the
      diagnosis of endometrial carcinoma. CONCLUSIONS: Size reduction of the
      hysteroscope is of greatest importance for reducing pain and risk of vasovagal
      reaction. In conclusion, the best approach in terms of ease, reliability,
      acceptability, and safety to patients in whom intrauterine exploration is
      indicated should be simple diagnostic mini-hysteroscopy using a small-diameter,
      rod lens hysteroscope with a single-flow diagnostic sheath, vaginoscopic
      approach, and fluid distention. In this way in about 90% of patients, a correct
      diagnosis and proper choice for eventual subsequent operative strategy can be
      obtained, without discomfort and risk.

PMID- 19749675
TI  - [Oncoplastic surgery for the treatment of breast cancer].
AB  - Surgery is still the gold standard in breast cancer. Also if the elective
      treatment, thanks to the adjuvant therapy, ha became more conservative than once
      was, breast surgery remains, in the mind of the woman affected by breast cancer,
      a demolitive surgery. The collaboration bet-ween the breast surgeon and the
      plastic surgeon has to be closer than it is, in order to obtain the total
      asportation of the tumor and an esthetic result that limits the psychological
      trauma to the woman. Oncoplastic surgery is the answer to these human and medical
      necessities, giving the correct approaches about breast volume, tumor volume,
      radicality of the treatment and esthetic outcome. This review will focus on
      different oncoplastic approaches, to help improving both the esthetic outcome of
      breast cancer resection and the likelihood of surgeons obtaining wide surgical
      margins in preparation for breast-conserving radiotherapy.

PMID- 19749676
TI  - Hair loss in women.
AB  - Hair loss in women is a very common clinical complaint, and is usually associated
      with severe emotional distress. In this article, the authors review the most
      common clinical causes of hair loss in women, and emphasize the role of hormonal
      changes in the regulation of hair loss and hair growth.

PMID- 19749677
TI  - [Low dose oral contraceptives: 30 microg are still used?].
AB  - The choice between oral contraceptives (OC) containing 30 or 20 microg of
      ethinylestradiol (EE) is founded on clinical sign and medical history of the
      women. Not always a lower dose of EE cause less side effects than an higher dose.
      Often 20-microg-EE OC induces menstrual cycle alterations and sexual
      dysfunctions, inducing the women to stop the treatment. Low estrogens
      concentration have a negative effect on external genital tract, with a consequent
      vaginal dryness and dispareunia. It is known that OC with 20-microg of EE
      determine a lower increase of sex hormone binding globulin compared to 30 mg EE
      and the consequence can be a reduction in antiandrogen effect of OC. OC
      containing 30 microg of EE have a positive effect on peak in young women,
      particularly in lean subjects. Moreover, 30 microg of EE induce a better ovarian
      suppression associated with a lower steroidal production during the week of
      interruption. Besides, 30-microg-EE OC works well in blocking ovarian cysts
      formation in women with endocrine dysfunctions like polycystic ovary syndrome or
      with previous luteal cysts. In conclusion, an OC with 30 microg of EE and an
      antiandrogen progestin is better than another with 20 microg of EE with the same
      progestin, because 30 microg of EE have a more powerful antiandrogenic action and
      guarantee very good cosmetics and endocrine results.

PMID- 19749678
TI  - [Nomegestrol acetate: clinical pharmacology].
AB  - Progestogens are used in clinical practice in some conditions. Their effects
      depend on their chemical structure, pharmacokinetics, pharmacodynamics, with
      important differences among various progestogens. Generally, progestins are
      classified according to their parent molecule, of which often they keep some
      features. Derivatives of 19-nor-progesterone are characterized by high
      selectivity of action on progestin receptor. In particular, nomegestrol acetate
      (NomAc) shows an important progestational potency, neutral gluco-lipid profile,
      and antigonadotropic activity. It is used for treating menstrual cycle disorders
      and for hormone replacement therapy in menopause in association with an estrogen.
      In future, thanks to its antigonadotropic activity, NomAc will be used in
      estroprogestin combinations in fertile women, thus taking advantage of its
      tolerability profile and obtaining numerous non-contraceptive benefits as well.

PMID- 19749679
TI  - Laparoscopic lateral ovarian transposition: a fertility sparing procedure.
AB  - This article reports the case of a 30-year-old woman who, in 2003, had diffuse
      large B-cell lymphoma of the left vaginal fornix, associated with sclerosis.
      After six chemoimmunotherapy cycles the patient underwent a laparoscopic
      procedure for lateral ovarian transposition to spare ovarian function before
      radiotherapy. Six months after the transposition the evaluation of ovarian
      function was performed. The hypothalamic-pituitary-ovary axis was normal. Three
      years after radiation therapy (2006) the patient spontaneously conceived. Her
      pregnancy proceeded regularly. She had an uneventful vaginal delivery. Lateral
      ovarian transposition with tubal anatomy preservation, which is an underused
      technique, can be successfully used to spare ovarian function in women who
      undergo pelvic radiotherapy and to let them achieve spontaneous pregnancy.

PMID- 19749680
TI  - The management of syncope in older adults.
AB  - Syncope is a frequent symptom in older patients. The diagnostic and therapeutic
      management may be complex, particularly in older adults with syncope and
      comorbidities or cognitive impairment. Morbidity related to syncope is more
      common in older persons and ranges from loss of confidence, depressive illness
      and fear of falling, to fractures and consequent institutionalization. Moreover,
      advan-ced age is associated with short and long-term morbidity and mortality
      after syncope. A standardized approach may obtain a definite diagnosis in more
      than 90% of the older patients with syncope and may reduce diagnostic tools and
      hospitalizations. The initial evaluation, including anamnesis, medical
      examination, orthostatic hypotension test and electrocardiogram (ECG), may be
      more difficult in the elderly, specially for the limited value of medical
      history, particularly for the certain diagnosis of neuro-mediated syncope. For
      this reason neuroautonomic assessment is an essential step to confirm a suspect
      of neuromediated syncope. Orthostatic blood pressure measurement, head up tilt
      test, carotid sinus massage and insertable cardiac monitor are safe and useful
      investigations, particularly in older patients. The most common causes of syncope
      in the older adults are orthostatic hypotension, carotid sinus hypersensitivity,
      neuromediated syncope and cardiac arrhythmias. The diagnostic evaluation and the
      treatment of cardiac syncope are similar in older and young patients and for this
      reason will not be discussed. In older patients unexplained falls could be
      related to syncope, particularly in patients with retrograde amnesia. There are
      no consistent differences in the treatment of syncope between older and younger
      population, but a specific approach is necessary for orthostatic hypotension,
      drug therapy and pacemaker implantation.

PMID- 19749681
TI  - Management of syncope in the Emergency Department.
AB  - Syncope is a common presenting complaint to the emergency department (ED). Its
      assessment is difficult. Some serious causes of syncope are transient and
      patients with a potentially life threatening condition may appear well by the
      time they reach the ED. Accurate history taking is vital and is often diagnostic
      whilst identification of a cardiac cause is associated with an increased
      mortality. This is related to underlying cardiac disease; patients presenting
      with syncope who have significant cardiac disease should be investigated
      thoroughly to determine the nature of the underlying heart disease and the cause
      of syncope. Early work suggested that as many as 30% of patients with cardiac
      syncope died within one year of presentation. This led to physicians admitting
      many patients with unexplained syncope however presently there is little evidence
      that focussed investigation, or even admission leads to an improved prognosis.
      Studies looking at syncope clinical decision units have though shown these to be
      of some benefit. Risk stratification studies on syncope in the ED have attempted
      to help emergency physicians target high-risk patients once those with clearly
      identifiable conditions have been identified and managed. These clinical decision
      rules have suffered from poor external validation and in the USA where many of
      these tools were developed, a universal consensus approach remains lacking.
      Although no individual tool has yet been successfully implemented into standard
      practice, as a whole they have probably enabled emergency physicians to become
      more aware of the risk factors that are likely to lead to poor outcome. It is
      likely that serious outcome in syncope although significant, is not quite as
      common as previously thought. Presently the American College of Emergency
      Physician (ACEP) guidelines are the most useful guidelines written for the
      emergency physician. With biochemical markers showing some promise, further work
      may lead to incorporation of these into existing clinical decision rules and
      guidelines to improve their sensitivity and specificity.

PMID- 19749682
TI  - Neurally-mediated sincope.
AB  - Syncope is a syndrome characterized by a relatively sudden, temporary and self
      terminating loss of consciousness; the causes may vary, but they have in common a
      temporary inadequacy of cerebral nutrient flow, usually due to a fall in systemic
      arterial pressure. However, while syncope is a common problem, it is only one
      explanation for episodic transient loss of consciousness (TLOC). Consequently,
      diagnostic evaluation should start with a broad consideration of real or
      seemingly real TLOC. Among those patients in whom TLOC is deemed to be due to
      ''true syncope'', the focus may then reasonably turn to assessing the various
      possible causes; in this regard, the neurally-mediated syncope syndromes are
      among the most frequently encountered. There are three common variations:
      vasovagal syncope (often termed the ''common'' faint), carotid sinus syndrome,
      and the so-called ''situational faints''. Defining whether the cause is due to a
      neurally-mediated reflex relies heavily on careful history taking and selected
      testing (e.g., tilt-test, carotid massage). These steps are important. Despite
      the fact that neurally-mediated faints are usually relatively benign from a
      mortality perspective, they are nevertheless only infrequently an isolated event;
      neurally-mediated syncope tends to recur, and physical injury resulting from
      falls or accidents, diminished quality-of-life, and possible restriction from
      employment or avocation are real concerns. Consequently, defining the specific
      form and developing an effective treatment strategy are crucial. In every case
      the goal should be to determine the cause of syncope with sufficient confidence
      to provide patients and family members with a reliable assessment of prognosis,
      recurrence risk, and treatment options.

PMID- 19749683
TI  - Implantable loop recorder for recurrent syncopes.
AB  - Syncope is a common disorder which may recur and impair the survival and the
      quality of life of the patients. The objective of the investigation of syncope is
      to diagnose the cardiac etiology, as mortality rate is high. Implantable loop
      recorder or insertable cardiac monitor (ICM) is a useful tool to establish a
      correlation between syncope and heart rhythm. About half of implanted patients
      complain of a new syncope and about 50% of these patients had cardiac rhythm
      disturbances on ICM. The most frequent is a sinus bradycardia or sinus arrest,
      but these results depend on the age of patients, resting electrocardiography
      (ECG) abnormalities and structural cardiac disease. A classification of the
      mechanisms of recurrent syncopes has been defined with the results of the ISSUE
      study, separating the syncope due to primary cardiac arrhythmia from neurally
      mediated syncope and from unknown syncope. The analysis of the presyncopal phase
      on the ICM restored ECG allows physicians to adapt the treatment (antiarrhytmic
      agents or pacemaker) and optimize the programming of the pacemaker when
      necessary. It is early recommended to implant the ICM in patients affected with
      syncope with normal physical examination, normal ECG and without structural heart
      disease and negative tilt testing. In the presence of cardiac disease, it is
      recommended to implant ICM after performing an electrophysiological study and
      tilt testing. In syncope patients with depressed left ventricular ejection
      fraction, the implantation of an automatic implantable cardiac defibrillator is
      preferable. The indications of the ICM tend to be extended to new syncope
      populations such as pediatric patients and epileptic population. Early
      application of ICM reduces the cost of the investigation of the patients
      suffering from syncope, especially when the electrophysiological study is
      avoided. In the future the implantation of the ICM should be early discussed in
      the Syncope Unit to shorten the duration and the cost of the hospitalizations of
      the patients with recurrent syncopes.

PMID- 19749684
TI  - Brugada syndrome: the prognostic dilemma and value of sincope.
AB  - Since its first description in 1992 as a new clinical entity, the Brugada
      syndrome has stimulated great interest among physicians and basic scientists. In
      2002 and 2005, two consensus conferences have respectively defined the diagnostic
      criteria for the syndrome. Currently the diagnosis of Brugada syndrome is based
      on a combination of clinical events (syncope and/or sudden cardiac death due to
      malignant ventricular arrhythmias) and electrocardiographic features
      (pathognomonic ST-segment elevation morphology). In the last years, many advances
      have been done in the knowledge about the genetic basis, the cellular mechanisms
      responsible for the typical electrocardiography features, susceptibility to
      ventricular arrhythmias and risk stratification. The implantable cardioverter
      defibrillator remains the only therapeutic option of proven efficacy for primary
      and secondary prophylaxis of sudden cardiac death. Identification of high risk
      subjects is one of the major goals in clinical decision-making. Syncope is
      ubiquitously recognized as a bad prognostic marker in Brugada syndrome. However,
      young individuals with this disease may suffer from vaso-vagal instead of
      arrhythmic syncope. The prognostic significance of syncope in patients with
      Brugada syndrome is discussed in this review.

PMID- 19749685
TI  - Syncope and carotid artery stenosis.
AB  - The carotid sinus plays an important role in systemic blood pressure regulation.
      The baroreceptor mechanism that underlies this physiological process is affected
      by underlying disease processes and therapeutic procedures. Stenosis of the
      carotid artery is seldom implicated in causation of syncope. Syncope caused by
      pathology at the carotid sinus and iatrogenically during interventional
      procedures is more frequently seen. The consequences of carotid stenosis and
      carotid hypersensitivity leading to cerebral hypoperfusion with syncope are
      described, along with recommendations related to screening in these patients.

PMID- 19749686
TI  - Head-up Tilt Table Testing: a state-of-the-art review.
AB  - Vasovagal syncope (VVS) is the commonest cause of syncope accounting for up to
      60% of all cases. The head-up tilt-table test (HUTT) was first described as a
      diagnostic test for VVS in 1986 and is now in widespread use as a research and
      diagnostic tool. Vasovagal syncope was previously thought to be confined to
      younger patients but with the introduction of HUTT, it is now being diagnosed
      with greater frequency in the elderly. Research into the physiological changes in
      susceptible individuals during HUTT has greatly increased our understanding of
      the pathophysiological processes underlying VVS; in particular, the hypotensive
      response during VVS is associated with sympathetic withdrawal rather than
      bradycardia alone. Various provocation agents, including nitrates, isoprotenerol
      and lower body negative pressure have been described to improve the diagnostic
      yield of the HUTT. Glyceryl trinitrate is now routinely administered during
      HUTTs. Individuals with typical presentations and infrequent episodes do not
      require investigation with HUTT as history alone is often diagnostic. The head-up
      tilt-table test is, however, required with atypical features, seizure activity,
      occupational issues, and is more likely to be required in older patients. The
      practicalities of conducting the HUTT and limitations of HUTTs are also
      discussed.

PMID- 19749687
TI  - Minor thalassemia may be a protective factor against Alzheimer?

PMID- 19749688
TI  - Tissue targeted embryonic chimeras: zebrafish gastrula cell transplantation.
AB  - Certain fundamental questions in the field of developmental biology can only be
      answered when cells are placed in novel environments or when small groups of
      cells in a larger context are altered. Watching how one cell interacts with and
      behaves in a unique environment is essential to characterizing cell functions.
      Determining how the localized misexpression of a specific protein influences
      surrounding cells provides insightful information on the roles that protein plays
      in a variety of developmental processes. Our lab uses the zebrafish model system
      to uniquely combine genetic approaches with classical transplantation techniques
      to generate genotypic or phenotypic chimeras. We study neuron-glial cell
      interactions during the formation of forebrain commissures in zebrafish. This
      video describes a method that allows our lab to investigate the role of
      astroglial populations in the diencephalon and the roles of specific guidance
      cues that influence projecting axons as they cross the midline. Due to their
      transparency zebrafish embryos are ideal models for this type of ectopic cell
      placement or localized gene misexpression. Tracking transplanted cells can be
      accomplished using a vital dye or a transgenic fish line expressing a fluorescent
      protein. We demonstrate here how to prepare donor embryos with a vital dye tracer
      for transplantation, as well as how to extract and transplant cells from one
      gastrula staged embryo to another. We present data showing ectopic GFP+
      transgenic cells within the forebrain of zebrafish embryos and characterize the
      location of these cells with respect to forebrain commissures. In addition, we
      show laser scanning confocal timelapse microscopy of Alexa 594 labeled cells
      transplanted into a GFP+ transgenic host embryo. These data provide evidence that
      gastrula staged transplantation enables the targeted positioning of ectopic cells
      to address a variety of questions in Developmental Biology.

PMID- 19749689
TI  - Facial aesthetics: is botulinum toxin treatment effective and safe? A systematic
      review of randomised controlled trials.
AB  - BACKGROUND: The use of botulinum toxin type A (BTA) in facial aesthetics for the
      treatment of wrinkles has recently become more popular as an alternative to
      surgical techniques. However, its true efficacy and potential adverse effects are
      still unclear. OBJECTIVES: The primary objective of this study was to review the
      efficacy of BTA in facial aesthetics. A secondary objective was to determine
      whether there are any adverse effects associated with the procedure of using BTA
      in facial aesthetics. SEARCH STRATEGY: We conducted literature searches on
      Medline (1977 to January 2009), Cochrane Controlled Trials Register (CENTRAL),
      EMBASE (1977 to January 2009) and CINAHL (1977 to January 2009). The search
      strategy also included reference lists of located articles and hand searching for
      randomised controlled trials (RCTs). We contacted authors of studies for further
      information where required. SELECTION CRITERIA: Randomised studies comparing BTA
      with placebo in facial aesthetics in a double-blind and crossover or parallel
      group design. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed
      trial quality and extracted data. The area of face injected, assessment methods,
      outcome measures, duration of action of BTA and associated adverse effects were
      reviewed. RESULTS AND DISCUSSION: A total of eleven RCTs involving 1,603 subjects
      were found, of which 1,203 were enrolled for treatment with BTA. The 11 trials
      were not directly comparable to each other due to differences in the areas of the
      face injected with BTA, length of study period, concentration of BTA used and
      outcome measures. The studies showed similar trends. The use of BTA showed
      improvements in facial wrinkles over placebo, with a peak effect reported at
      around one month and the effects lasting between 4-6 months. No studies reported
      any severe adverse effects. The incidence of blepharoptosis in glabellar lines
      treated with BTA was reported to be between 0-5.4%, and may be related to the
      technique of injection into the muscles. The incidence of other side-effects such
      as headache, pain at injection site and mild bruising was similar in both the BTA
      and placebo groups. AUTHORS' CONCLUSIONS: The use of BTA in facial aesthetics is
      more effective than placebo. The incidence of adverse effects associated with BTA
      is similar to placebo, with the exception of blepharoptosis which is reported to
      be 0-5.4% after treatment of glabellar lines with BTA.

PMID- 19749690
TI  - In search of quality.

PMID- 19749691
TI  - Unusual gingivitis.

PMID- 19749692
TI  - Ignored report.

PMID- 19749693
TI  - Managing emergencies.

PMID- 19749694
TI  - Hookah epidemic.

PMID- 19749695
TI  - Rights regained.

PMID- 19749696
TI  - Humiliation.

PMID- 19749697
TI  - Work cohesively.

PMID- 19749698
TI  - Oil therapy.

PMID- 19749699
TI  - Slogan standards.

PMID- 19749700
TI  - Accepting responsibility.

PMID- 19749701
TI  - Dental decisions.

PMID- 19749702
TI  - X-ray burn out.

PMID- 19749703
TI  - Mouth cancer increase attributed to alcohol.

PMID- 19749711
TI  - Digital dental photography. Part 9: post-image capture processing.
AB  - Having successfully taken a digital image, the next step is deciding what to do
      with it. Should it be cropped, correctly orientated, manipulated, compressed,
      scaled, sharpened, archived (and if so, which file format is the most suitable),
      or even discarded? The premise of this part of our series is to answer these and
      other questions related to post-production of a digital image.

PMID- 19749712
TI  - An unusual soft tissue radiopacity--radiographic appearance of a dermal filler.
AB  - We present a case that describes the radiographic findings of Radiesse, a calcium
      hydroxyapatitie-based dermal filler. This dermal filler was detected during
      radiographic examination for implant treatment planning. This case illustrates
      the typical radiographic appearance of this material and the importance of
      differentiating it from pathological conditions.

PMID- 19749719
TI  - An evaluation of a pilot study of a web-based educational initiative for
      educating and training undergraduate dental students in infection prevention.
AB  - OBJECTIVE: Evaluate the views of undergraduate dental students on a pilot web
      based e-learning programme to establish its merit in providing education in
      infection prevention and control. The initiative was commissioned by NHS
      Education for Scotland as an educational resource for healthcare workers. Design,
      SAMPLE AND SETTING: This was a retrospective analysis of questionnaire data from
      the first cohort of dental students completing the programme in a UK dental
      school. METHODS: Dental students studied the course during the first three years
      of the curriculum. Data were collated via an anonymous semi-structured
      questionnaire distributed at a post-course feedback session. RESULTS: Sixty
      percent (51/85) of students returned questionnaires with 90% stating their
      knowledge of infection control had improved. Specific areas included: undertaking
      infection control audits (88%), managing sharps injuries (73%), use of personal
      protective equipment (55%) and hand hygiene (55%). On the other hand, 72%
      perceived the programme as too generic with just over half advocating a resource
      more relevant to dentistry. CONCLUSION: The programme has the potential to be a
      useful teaching aid but requires modification. A customised version for dental
      students has subsequently been commissioned.

PMID- 19749720
TI  - Orthodontic therapists--the first Bristol cohort.
AB  - This paper outlines the development of the training of orthodontic therapists in
      the UK, the experiences of the first cohort to pass through the Bristol course,
      the roles and responsibilities of the therapist and possible issues with future
      orthodontic manpower planning.

PMID- 19749736
TI  - Dentists in mountain rescue.
AB  - Dental practitioners often lead busy lives. It is amazing how diverse their
      activities can be after the surgery door has closed. This short article describes
      how our colleagues volunteer to serve the public in one difficult and hazardous
      environment - the mountainsides of Cumbria.

PMID- 19749739
TI  - Heparanase expression by Barrett's epithelium and during esophageal carcinoma
      progression.
AB  - Enzymatic activity responsible for the cleavage of heparan sulfate, commonly
      known as heparanase, is abundant in tumor-derived cells. Heparanase cleaves
      heparan sulfate side chains, presumably at sites of low sulfation, thus
      facilitating structural alterations of the extracellular matrix and basement
      membrane underlying epithelial and endothelial cells. Traditionally, heparanase
      activity was correlated with the metastatic potential of tumor-derived cells,
      attributed to enhanced cell dissemination as a consequence of heparan sulfate
      cleavage and remodeling of the extracellular matrix barrier. More recently,
      heparanase upregulation was documented in an increasing number of human
      carcinomas and hematological malignancies, correlating with increased tumor
      metastasis, vascular density, and shorter post-operative survival of cancer
      patients. Although heparanase upregulation and its pro-malignant features are
      well documented, the instance of its induction in the course of tumor development
      was less investigated. Here, we used immunohistochemical analysis to investigate
      heparanase expression in normal esophagus, Barrett's esophagus without dysplasia,
      Barrett's esophagus with low-grade dysplasia, Barrett's esophagus with high-grade
      dysplasia, and adenocarcinoma of the esophagus. We report that heparanase
      expression is already induced in Barrett's epithelium without dysplasia, and is
      further increased during progression through distinct pathological stages,
      namely, low-grade dysplasia, high-grade dysplasia, and adenocarcinoma. Notably,
      heparanase induction correlated with increased cell proliferation index revealed
      by Ki-67 staining. These findings suggest that heparanase function is not limited
      to the process of tumor metastasis, but rather is engaged at the early stages of
      esophagus carcinoma initiation and progression.

PMID- 19749740
TI  - Clinicopathological significance of the CRTC3-MAML2 fusion transcript in
      mucoepidermoid carcinoma.
AB  - Mucoepidermoid carcinoma is the most common primary malignancy of the salivary
      gland. We and others showed that CRTC1-MAML2 gene fusion was associated with
      favorable clinicopathological tumor features. Recently, a novel gene fusion,
      CRTC3-MAML2, was reported as a rare gene alteration in a case of mucoepidermoid
      carcinoma. However, its frequency and clinicopathological significance remains
      unclear. In all, 101 cases of mucoepidermoid carcinoma and 89 cases of non
      mucoepidermoid carcinoma of the salivary gland were analyzed, and RNA was
      extracted from formalin-fixed, paraffin-embedded specimens. In the CRTC family,
      there have been three genes, CRTC1, CRTC2, and CRTC3. We developed reverse
      transcription-polymerase chain reaction (RT-PCR) assays for CRTC1-MAML2, CRTC2
      MAML2, and CRTC3-MAML2 fusions. Clinicopathological data of the patients were
      obtained from their clinical records. Of 101 cases of mucoepidermoid carcinoma,
      34 (34%) and 6 (6%) were positive for CRTC1-MAML2 and CRTC3-MAML2 fusion
      transcripts. However, in the 89 cases of non-mucoepidermoid carcinoma, neither
      transcript was noted. In the former cases, CRTC1-MAML2 and CRTC3-MAML2 fusions
      were mutually exclusive. The other fusion, CRTC2-MAML2, was not detected. We
      confirmed that the clinicopathological features of CRTC1-MAML2-positive
      mucoepidermoid carcinomas indicated an indolent course. CRTC3-MAML2-positive
      mucoepidermoid carcinomas also had clinicopathologically favorable features; all
      cases showed a less advanced clinical stage, negative nodal metastasis, no high
      grade tumor histology, and no recurrence or tumor-related death after surgical
      resection of the tumor. It is interesting to note that patients with CRTC3-MAML2
      positive tumors (mean 36 years of age) were significantly younger that those with
      the CRTC1-MAML2 fusion (55 years) and those with fusion-negative tumors (58
      years). In conclusion, CRTC3-MAML2 fusion, which is mutually exclusive with CRTC1
      MAML2 fusion and specific to mucoepidermoid carcinoma, may be detected more
      frequently than previously expected. Mucoepidermoid carcinomas possessing CRTC3
      MAML2 fusion may be associated with favorable clinicopathological features and
      patients may be younger than those with CRTC1-MAML2 fusion or those with no
      detectable gene fusion.

PMID- 19749741
TI  - Atmospheric carbon dioxide through the Eocene-Oligocene climate transition.
AB  - Geological and geochemical evidence indicates that the Antarctic ice sheet formed
      during the Eocene-Oligocene transition, 33.5-34.0 million years ago. Modelling
      studies suggest that such ice-sheet formation might have been triggered when
      atmospheric carbon dioxide levels (pCO2atm) fell below a critical threshold of
      approximately 750 p.p.m.v., but the timing and magnitude of pCO2atm relative to
      the evolution of the ice sheet has remained unclear. Here we use the boron
      isotope pH proxy on exceptionally well-preserved carbonate microfossils from a
      recently discovered geological section in Tanzania to estimate pCO2atm before,
      during and after the climate transition. Our data suggest that are reduction in
      pCO2atm occurred before the main phase of ice growth,followed by a sharp recovery
      to pre-transition values and then a more gradual decline. During maximum ice
      sheet growth, pCO2atm was between approximately 450 and approximately 1,500
      p.p.m.v., with a central estimate of approximately 760 p.p.m.v. The ice cap
      survived the period of pCO2atm recovery,although possibly with some reduction in
      its volume, implying (as models predict) a nonlinear response to climate forcing
      during melting. Overall, our results confirm the central role of declining
      pCO2atm in the development of the Antarctic ice sheet (in broad agreement with
      carbon cycle modelling) and help to constrain mechanisms and feedbacks associated
      with the Earth's biggest climate switch of the past 65 Myr.

PMID- 19749742
TI  - Spatiotemporal control of cell signalling using a light-switchable protein
      interaction.
AB  - Genetically encodable optical reporters, such as green fluorescent protein, have
      revolutionized the observation and measurement of cellular states. However, the
      inverse challenge of using light to control precisely cellular behaviour has only
      recently begun to be addressed; semi-synthetic chromophore-tethered receptors and
      naturally occurring channel rhodopsins have been used to perturb directly
      neuronal networks. The difficulty of engineering light-sensitive proteins remains
      a significant impediment to the optical control of most cell-biological
      processes. Here we demonstrate the use of a new genetically encoded light-control
      system based on an optimized, reversible protein-protein interaction from the
      phytochrome signalling network of Arabidopsis thaliana. Because protein-protein
      interactions are one of the most general currencies of cellular information, this
      system can, in principle, be generically used to control diverse functions. Here
      we show that this system can be used to translocate target proteins precisely and
      reversibly to the membrane with micrometre spatial resolution and at the second
      timescale. We show that light-gated translocation of the upstream activators of
      Rho-family GTPases, which control the actin cytoskeleton, can be used to
      precisely reshape and direct the cell morphology of mammalian cells. The light
      gated protein-protein interaction that has been optimized here should be useful
      for the design of diverse light-programmable reagents, potentially enabling a new
      generation of perturbative, quantitative experiments in cell biology.

PMID- 19749743
TI  - How curved membranes recruit amphipathic helices and protein anchoring motifs.
AB  - Lipids and several specialized proteins are thought to be able to sense the
      curvature of membranes (MC). Here we used quantitative fluorescence microscopy to
      measure curvature-selective binding of amphipathic motifs on single liposomes 50
      700 nm in diameter. Our results revealed that sensing is predominantly mediated
      by a higher density of binding sites on curved membranes instead of higher
      affinity. We proposed a model based on curvature-induced defects in lipid packing
      that related these findings to lipid sorting and accurately predicted the
      existence of a new ubiquitous class of curvature sensors: membrane-anchored
      proteins. The fact that unrelated structural motifs such as alpha-helices and
      alkyl chains sense MC led us to propose that MC sensing is a generic property of
      curved membranes rather than a property of the anchoring molecules. We therefore
      anticipate that MC will promote the redistribution of proteins that are anchored
      in membranes through other types of hydrophobic moieties.

PMID- 19749744
TI  - The non-coding RNA of the multidrug resistance-linked vault particle encodes
      multiple regulatory small RNAs.
AB  - Vault particles are conserved organelles implicated in multidrug resistance and
      intracellular transport. They contain three different proteins and non-coding
      vault RNAs (vRNAs). Here we show that human vRNAs produce several small RNAs
      (svRNAs) by mechanisms different from those in the canonical microRNA (miRNA)
      pathway. At least one of these svRNAs, svRNAb, associates with Argonaute proteins
      to guide sequence-specific cleavage and regulate gene expression similarly to
      miRNAs. We demonstrate that svRNAb downregulates CYP3A4, a key enzyme in drug
      metabolism. Our findings expand the repertoire of small regulatory RNAs and
      assign, for the first time, a function to vRNAs that may help explain the
      association between vault particles and drug resistance.

PMID- 19749745
TI  - Listeria monocytogenes ActA-mediated escape from autophagic recognition.
AB  - Autophagy degrades unnecessary organelles and misfolded protein aggregates, as
      well as cytoplasm-invading bacteria. Nevertheless, the bacteria Listeria
      monocytogenes efficiently escapes autophagy. We show here that recruitment of the
      Arp2/3 complex and Ena/VASP, via the bacterial ActA protein, to the bacterial
      surface disguises the bacteria from autophagic recognition, an activity that is
      independent of the ability to mediate bacterial motility. L. monocytogenes
      expressing ActA mutants that lack the ability to recruit the host proteins
      initially underwent ubiquitylation, followed by recruitment of p62 (also known as
      SQSTM1) and LC3, before finally undergoing autophagy. The ability of ActA to
      mediate protection from ubiquitylation was further demonstrated by generating
      aggregate-prone GFP-ActA-Q79C and GFP-ActA-170(*) chimaeras, consisting of GFP
      (green fluorescent protein), the ActA protein and segments of polyQ or Golgi
      membrane protein GCP170 (ref. 6). GFP-ActA-Q79C and GFP-ActA-170(*) formed
      aggregates in the host cell cytoplasm, however, these ActA-containing aggregates
      were not targeted for association with ubiquitin and p62. Our findings indicate
      that ActA-mediated host protein recruitment is a unique bacterial disguise tactic
      to escape from autophagy.

PMID- 19749746
TI  - C/EBPalpha and beta couple interfollicular keratinocyte proliferation arrest to
      commitment and terminal differentiation.
AB  - The transcriptional regulators that couple interfollicular basal keratinocyte
      proliferation arrest to commitment and differentiation are yet to be identified.
      Here we report that the basic region leucine zipper transcription factors
      C/EBPalpha and C/EBPbeta are co-expressed in basal keratinocytes, and are
      coordinately upregulated as keratinocytes exit the basal layer and undergo
      terminal differentiation. Mice lacking both C/EBPalpha and beta in the epidermis
      showed increased proliferation of basal keratinocytes and impaired commitment to
      differentiation. This led to ectopic expression of keratin 14 (K14) and DeltaNp63
      in suprabasal cells, decreased expression of spinous and granular layer proteins,
      parakeratosis and defective epidermal water barrier function. Knock-in
      mutagenesis revealed that C/EBP-E2F interaction was required for control of
      interfollicular epidermis (IFE) keratinocyte proliferation, but not for induction
      of spinous and granular layer markers, whereas C/EBP DNA binding was required for
      DeltaNp63 downregulation and K1/K10 induction. Finally, loss of C/EBPalpha/beta
      induced stem cell gene expression signatures in the epidermis. C/EBPs, therefore,
      couple basal keratinocyte cell cycle exit to commitment to differentiation
      through E2F repression and DNA binding, respectively, and may act to restrict the
      epidermal stem cell compartment.

PMID- 19749747
TI  - AP2gamma regulates basal progenitor fate in a region- and layer-specific manner
      in the developing cortex.
AB  - An important feature of the cerebral cortex is its layered organization, which is
      modulated in an area-specific manner. We found that the transcription factor
      AP2gamma regulates laminar fate in a region-specific manner. Deletion of AP2gamma
      (also known as Tcfap2c) during development resulted in a specific reduction of
      upper layer neurons in the occipital cortex, leading to impaired function and
      enhanced plasticity of the adult visual cortex. AP2gamma functions in apical
      progenitors, and its absence resulted in mis-specification of basal progenitors
      in the occipital cortex at the time at which upper layer neurons were generated.
      AP2gamma directly regulated the basal progenitor fate determinants Math3 (also
      known as Neurod4) and Tbr2, and its overexpression promoted the generation of
      layer II/III neurons in a time- and region-specific manner. Thus, AP2gamma acts
      as a regulator of basal progenitor fate, linking regional and laminar
      specification in the mouse developing cerebral cortex.

PMID- 19749748
TI  - Coding of stimulus sequences by population responses in visual cortex.
AB  - Neuronal populations in sensory cortex represent time-changing sensory input
      through a spatiotemporal code. What are the rules that govern this code? We
      measured membrane potentials and spikes from neuronal populations in cat visual
      cortex (V1) using voltage-sensitive dyes and electrode arrays. We first
      characterized the population response to a single orientation. As response
      amplitude grew, the population tuning width remained constant for membrane
      potential responses and became progressively sharper for spike responses. We then
      asked how these single-orientation responses combine to code for successive
      orientations. We found that they combined through simple linear summation.
      Linearity, however, was violated after stimulus offset, when responses exhibited
      an unexplained persistence. As a result of linearity, the interactions between
      responses to successive stimuli were minimal. Our results indicate that higher
      cortical areas may reconstruct the stimulus sequence from V1 population responses
      through a simple instantaneous decoder. Therefore, spatial and temporal codes in
      area V1 operate largely independently.

PMID- 19749749
TI  - Fragmentation of grid cell maps in a multicompartment environment.
AB  - To determine whether entorhinal spatial representations are continuous or
      fragmented, we recorded neural activity in grid cells while rats ran through a
      stack of interconnected, zig-zagged compartments of equal shape and orientation
      (a hairpin maze). The distribution of spatial firing fields was markedly similar
      across all compartments in which running occurred in the same direction, implying
      that the grid representation was fragmented into repeating submaps. Activity at
      neighboring positions was least correlated at the transitions between different
      arms, indicating that the map split regularly at the turning points. We saw
      similar discontinuities among place cells in the hippocampus. No fragmentation
      was observed when the rats followed similar trajectories in the absence of
      internal walls, implying that stereotypic behavior alone cannot explain the
      compartmentalization. These results indicate that spatial environments are
      represented in entorhinal cortex and hippocampus as a mosaic of discrete submaps
      that correspond to the geometric structure of the space.

PMID- 19749750
TI  - Selective suppression of hippocampal ripples impairs spatial memory.
AB  - Sharp wave-ripple (SPW-R) complexes in the hippocampus-entorhinal cortex are
      believed to be important for transferring labile memories from the hippocampus to
      the neocortex for long-term storage. We found that selective elimination of SPW
      Rs during post-training consolidation periods resulted in performance impairment
      in rats trained on a hippocampus-dependent spatial memory task. Our results
      provide evidence for a prominent role of hippocampal SPW-Rs in memory
      consolidation.

PMID- 19749751
TI  - Nicotine activates the chemosensory cation channel TRPA1.
AB  - Topical application of nicotine, as used in nicotine replacement therapies,
      causes irritation of the mucosa and skin. This reaction has been attributed to
      activation of nicotinic acetylcholine receptors (nAChRs) in chemosensory neurons.
      In contrast with this view, we found that the chemosensory cation channel
      transient receptor potential A1 (TRPA1) is crucially involved in nicotine-induced
      irritation. We found that micromolar concentrations of nicotine activated
      heterologously expressed mouse and human TRPA1. Nicotine acted in a membrane
      delimited manner, stabilizing the open state(s) and destabilizing the closed
      state(s) of the channel. In the presence of the general nAChR blocker
      hexamethonium, nociceptive neurons showed nicotine-induced responses that were
      strongly reduced in TRPA1-deficient mice. Finally, TRPA1 mediated the mouse
      airway constriction reflex to nasal instillation of nicotine. The identification
      of TRPA1 as a nicotine target suggests that existing models of nicotine-induced
      irritation should be revised and may facilitate the development of smoking
      cessation therapies with less adverse effects.

PMID- 19749752
TI  - Following evolutionary paths to protein-protein interactions with high affinity
      and selectivity.
AB  - How do intricate multi-residue features such as protein-protein interfaces
      evolve? To address this question, we evolved a new colicin-immunity binding
      interaction. We started with Im9, which inhibits its cognate DNase ColE9 at 10(
      14) M affinity, and evolved it toward ColE7, which it inhibits promiscuously (Kd
      > 10(-8) M). Iterative rounds of random mutagenesis and selection toward higher
      affinity for ColE7, and selectivity (against ColE9 inhibition), led to an
      approximately 10(5)-fold increase in affinity and a 10(8)-fold increase in
      selectivity. Analysis of intermediates along the evolved variants revealed that
      changes in the binding configuration of the Im protein uncovered a latent set of
      interactions, thus providing the key to the rapid divergence of new Im7 variants.
      Overall, protein-protein interfaces seem to share the evolvability features of
      enzymes, that is, the exploitation of promiscuous interactions and alternative
      binding configurations via 'generalist' intermediates, and the key role of
      compensatory stabilizing mutations in facilitating the divergence of new
      functions.

PMID- 19749753
TI  - Structural basis for autoregulation of the zinc transporter YiiP.
AB  - Zinc transporters have crucial roles in cellular zinc homeostatic control. The
      2.9-A resolution structure of the zinc transporter YiiP from Escherichia coli
      reveals a richly charged dimer interface stabilized by zinc binding. Site
      directed fluorescence resonance energy transfer (FRET) measurements and mutation
      activity analysis suggest that zinc binding triggers hinge movements of two
      electrically repulsive cytoplasmic domains pivoting around four salt bridges
      situated at the juncture of the cytoplasmic and transmembrane domains. These
      highly conserved salt bridges interlock transmembrane helices at the dimer
      interface, where they are well positioned to transmit zinc-induced interdomain
      movements to reorient transmembrane helices, thereby modulating coordination
      geometry of the active site for zinc transport. The cytoplasmic domain of YiiP is
      a structural mimic of metal-trafficking proteins and the metal-binding domains of
      metal-transporting P-type ATPases. The use of this common structural module to
      regulate metal coordination chemistry may enable a tunable transport activity in
      response to cytoplasmic metal fluctuations.

PMID- 19749754
TI  - Splice site strength-dependent activity and genetic buffering by poly-G runs.
AB  - Pre-mRNA splicing is regulated through the combinatorial activity of RNA motifs,
      including splice sites and splicing regulatory elements. Here we show that the
      activity of the G-run (polyguanine sequence) class of splicing enhancer elements
      is approximately 4-fold higher when adjacent to intermediate strength 5' splice
      sites (ss) than when adjacent to weak 5' ss, and approximately 1.3-fold higher
      relative to strong 5' ss. We observed this dependence on 5' ss strength in both
      splicing reporters and in global microarray and mRNA-Seq analyses of splicing
      changes following RNA interference against heterogeneous nuclear
      ribonucleoprotein (hnRNP) H, which cross-linked to G-runs adjacent to many
      regulated exons. An exon's responsiveness to changes in hnRNP H levels therefore
      depends in a complex way on G-run abundance and 5' ss strength. This pattern of
      activity enables G-runs and hnRNP H to buffer the effects of 5' ss mutations,
      augmenting both the frequency of 5' ss polymorphism and the evolution of new
      splicing patterns. Certain other splicing factors may function similarly.

PMID- 19749755
TI  - Tertiary structure checkpoint at anticodon loop modification in tRNA functional
      maturation.
AB  - tRNA precursors undergo a maturation process, involving nucleotide modifications
      and folding into the L-shaped tertiary structure. The N1-methylguanosine at
      position 37 (m1G37), 3' adjacent to the anticodon, is essential for translational
      fidelity and efficiency. In archaea and eukaryotes, Trm5 introduces the m1G37
      modification into all tRNAs bearing G37. Here we report the crystal structures of
      archaeal Trm5 (aTrm5) in complex with tRNA(Leu) or tRNA(Cys). The D2-D3 domains
      of aTrm5 discover and modify G37, independently of the tRNA sequences. D1 is
      connected to D2-D3 through a flexible linker and is designed to recognize the
      shape of the tRNA outer corner, as a hallmark of the completed L shape formation.
      This interaction by D1 lowers the K(m) value for tRNA, enabling the D2-D3
      catalysis. Thus, we propose that aTrm5 provides the tertiary structure checkpoint
      in tRNA maturation.

PMID- 19749756
TI  - Interferon-alfa, interferon-lambda and hepatitis C.

PMID- 19749757
TI  - Genome-wide association of IL28B with response to pegylated interferon-alpha and
      ribavirin therapy for chronic hepatitis C.
AB  - The recommended treatment for patients with chronic hepatitis C, pegylated
      interferon-alpha (PEG-IFN-alpha) plus ribavirin (RBV), does not provide sustained
      virologic response (SVR) in all patients. We report a genome-wide association
      study (GWAS) to null virological response (NVR) in the treatment of patients with
      hepatitis C virus (HCV) genotype 1 within a Japanese population. We found two
      SNPs near the gene IL28B on chromosome 19 to be strongly associated with NVR
      (rs12980275, P = 1.93 x 10(-13), and rs8099917, 3.11 x 10(-15)). We replicated
      these associations in an independent cohort (combined P values, 2.84 x 10(-27)
      (OR = 17.7; 95% CI = 10.0-31.3) and 2.68 x 10(-32) (OR = 27.1; 95% CI = 14.6
      50.3), respectively). Compared to NVR, these SNPs were also associated with SVR
      (rs12980275, P = 3.99 x 10(-24), and rs8099917, P = 1.11 x 10(-27)). In further
      fine mapping of the region, seven SNPs (rs8105790, rs11881222, rs8103142,
      rs28416813, rs4803219, rs8099917 and rs7248668) located in the IL28B region
      showed the most significant associations (P = 5.52 x 10(-28)-2.68 x 10(-32); OR =
      22.3-27.1). Real-time quantitative PCR assays in peripheral blood mononuclear
      cells showed lower IL28B expression levels in individuals carrying the minor
      alleles (P = 0.015).

PMID- 19749758
TI  - IL28B is associated with response to chronic hepatitis C interferon-alpha and
      ribavirin therapy.
AB  - Hepatitis C virus (HCV) infects 3% of the world's population. Treatment of
      chronic HCV consists of a combination of PEGylated interferon-alpha (PEG-IFN
      alpha) and ribavirin (RBV). To identify genetic variants associated with HCV
      treatment response, we conducted a genome-wide association study of sustained
      virological response (SVR) to PEG-IFN-alpha/RBV combination therapy in 293
      Australian individuals with genotype 1 chronic hepatitis C, with validation in an
      independent replication cohort consisting of 555 individuals. We report an
      association to SVR within the gene region encoding interleukin 28B (IL28B, also
      called IFNlambda3; rs8099917 combined P = 9.25 x 10(-9), OR = 1.98, 95% CI = 1.57
      2.52). IL28B contributes to viral resistance and is known to be upregulated by
      interferons and by RNA virus infection. These data suggest that host genetics may
      be useful for the prediction of drug response, and they also support the
      investigation of the role of IL28B in the treatment of HCV and in other diseases
      treated with IFN-alpha.

PMID- 19749759
TI  - A tumor suppressor activity of Drosophila Polycomb genes mediated by JAK-STAT
      signaling.
AB  - A prevailing paradigm posits that Polycomb Group (PcG) proteins maintain stem
      cell identity by repressing differentiation genes, and abundant evidence points
      to an oncogenic role for PcG proteins in human cancer. Here we show using
      Drosophila melanogaster that a conventional PcG complex can also have a potent
      tumor suppressor activity. Mutations in any core PRC1 component cause pronounced
      hyperproliferation of eye imaginal tissue, accompanied by deregulation of
      epithelial architecture. The mitogenic JAK-STAT pathway is strongly and
      specifically activated in mutant tissue; activation is driven by transcriptional
      upregulation of Unpaired (Upd, also known as Outstretched, Os) family ligands. We
      show here that upd genes are direct targets of PcG-mediated repression in
      imaginal discs. Ectopic JAK-STAT activity is sufficient to induce
      overproliferation, whereas reduction of JAK-STAT activity suppresses the PRC1
      mutant tumor phenotype. These findings show that PcG proteins can restrict growth
      directly by silencing mitogenic signaling pathways, shedding light on an
      epigenetic mechanism underlying tumor suppression.

PMID- 19749760
TI  - Polyhomeotic has a tumor suppressor activity mediated by repression of Notch
      signaling.
AB  - Polycomb Group (PcG) proteins silence critical developmental genes and modulate
      cell proliferation. Using the Drosophila melanogaster eye as a model system, we
      show that cells with mutations in the gene locus (ph) that encodes the PcG
      protein Polyhomeotic (PH) overproliferate and lose both the ability to
      differentiate and their normal polarity. They invade the neighboring tissues and,
      when combined with an activated form of the Ras proto-oncogene, they trigger the
      formation of metastases. PcG proteins bind to multiple genes in the Notch pathway
      and control their transcription as well as Notch signaling. The massive cell
      autonomous overproliferation of ph mutant cell clones can be rescued by ectopic
      expression of a dominant negative form of Notch or by RNA interference (RNAi)
      mediated repression of Notch. Conversely, overexpression of ph induces a small
      eye phenotype that is rescued by activation of Notch signaling. These data show
      that ph is a tumor suppressor locus that controls cellular proliferation by
      silencing multiple Notch signaling components.

PMID- 19749761
TI  - Proteomics strategy for quantitative protein interaction profiling in cell
      extracts.
AB  - We report a proteomics strategy to both identify and quantify cellular target
      protein interactions with externally introduced ligands. We determined
      dissociation constants for target proteins interacting with the ligand of
      interest by combining quantitative mass spectrometry with a defined set of
      affinity purification experiments. We demonstrate the general utility of this
      methodology in interaction studies involving small-molecule kinase inhibitors, a
      tyrosine-phosphorylated peptide and an antibody as affinity ligands.

PMID- 19749762
TI  - A Flp-nick system to study repair of a single protein-bound nick in vivo.
AB  - We present the Flp-nick system, which allows introduction of a protein-bound nick
      at a single genomic site in Saccharomyces cerevisiae and thus mimics a stabilized
      topoisomerase I-DNA cleavage complex. We took advantage of a mutant Flp
      recombinase that can introduce a nick at a specific Flp recombinase recognition
      target site that has been integrated in the yeast genome. The genetic requirement
      for cells to cope with this insult is the same as for cells treated with
      camptothecin, which traps topoisomerase I-DNA cleavage complexes genome-wide.
      Hence, a single protein-bound nick is enough to kill cells if functional repair
      pathways are lacking. The Flp-nick system can be used to dissect repair,
      checkpoint and replication fork management pathways activated by a single genomic
      insult, and it allows the study of events at the damage site, which so far has
      been impossible to address.

PMID- 19749763
TI  - The basic leucine zipper transcription factor E4BP4 is essential for natural
      killer cell development.
AB  - Natural killer (NK) cells are a subset of lymphocytes crucial for innate immunity
      and modification of adaptive immune responses. In contrast to commitment to the T
      cell or B cell lineage, little is known about NK cell lineage commitment. Here we
      show that the basic leucine zipper (bZIP) transcription factor E4BP4 (also called
      NFIL3) is essential for generation of the NK cell lineage. E4BP4-deficient mice
      (Nfil3(-/-); called 'E4bp4(-/-)' here) had B cells, T cells and NKT cells but
      specifically lack NK cells and showed severely impaired NK cell-mediated
      cytotoxicity. Overexpression of E4bp4 was sufficient to increase NK cell
      production from hematopoietic progenitor cells. E4BP4 acted in a cell-intrinsic
      manner 'downstream' of the interleukin 15 receptor (IL-15R) and through the
      transcription factor Id2. E4bp4(-/-) mice may provide a model for definitive
      analysis of the contribution of NK cells to immune responses and pathologies.

PMID- 19749764
TI  - Transcription elongation factor ELL2 directs immunoglobulin secretion in plasma
      cells by stimulating altered RNA processing.
AB  - Immunoglobulin secretion is modulated by competition between the use of a weak
      promoter-proximal poly(A) site and a nonconsensus splice site in the final
      secretory-specific exon of the heavy chain pre-mRNA. The RNA polymerase II
      transcription elongation factor ELL2, which is induced in plasma cells, enhanced
      both polyadenylation and exon skipping with the gene encoding the immunoglobulin
      heavy-chain complex (Igh) and reporter constructs. Lowering ELL2 expression by
      transfection of heterogenous ribonucleoprotein F (hnRNP F) or small interfering
      RNA resulted in lower abundance of secretory-specific forms of immunoglobulin
      heavy-chain mRNA. ELL2 and the polyadenylation factor CstF-64 tracked together
      with RNA polymerase II across the Igh mu- and gamma-gene segments; the
      association of both factors was blocked by ELL2-specific small interfering RNA.
      Thus, loading of ELL2 and CstF-64 on RNA polymerase II was linked, caused
      enhanced use of the proximal poly(A) site and was necessary for processing of
      immunoglobulin heavy-chain mRNA.

PMID- 19749765
TI  - The effect of nanometre-scale structure on interfacial energy.
AB  - Natural surfaces are often structured with nanometre-scale domains, yet a
      framework providing a quantitative understanding of how nanostructure affects
      interfacial energy, gamma(SL), is lacking. Conventional continuum thermodynamics
      treats gamma(SL) solely as a function of average composition, ignoring structure.
      Here we show that, when a surface has domains commensurate in size with solvent
      molecules, gamma(SL) is determined not only by its average composition but also
      by a structural component that causes gamma(SL) to deviate from the continuum
      prediction by a substantial amount, as much as 20% in our system. By contrasting
      surfaces coated with either molecular- (<2 nm) or larger-scale domains (>5 nm),
      we find that whereas the latter surfaces have the expected linear dependence of
      gamma(SL) on surface composition, the former show a markedly different non
      monotonic trend. Molecular dynamics simulations show how the organization of the
      solvent molecules at the interface is controlled by the nanostructured surface,
      which in turn appreciably modifies gamma(SL).

PMID- 19749766
TI  - The effect of three-dimensional morphology on the efficiency of hybrid polymer
      solar cells.
AB  - The efficiency of polymer solar cells critically depends on the intimacy of
      mixing of the donor and acceptor semiconductors used in these devices to create
      charges and on the presence of unhindered percolation pathways in the individual
      components to transport holes and electrons. The visualization of these bulk
      heterojunction morphologies in three dimensions has been challenging and has
      hampered progress in this area. Here, we spatially resolve the morphology of 2%
      efficient hybrid solar cells consisting of poly(3-hexylthiophene) as the donor
      and ZnO as the acceptor in the nanometre range by electron tomography. The
      morphology is statistically analysed for spherical contact distance and
      percolation pathways. Together with solving the three-dimensional exciton
      diffusion equation, a consistent and quantitative correlation between solar-cell
      performance, photophysical data and the three-dimensional morphology has been
      obtained for devices with different layer thicknesses that enables
      differentiating between generation and transport as limiting factors to
      performance.

PMID- 19749768
TI  - Hindered rolling and friction anisotropy in supported carbon nanotubes.
AB  - Carbon nanotubes (CNTs) are well known for their exceptional thermal, mechanical
      and electrical properties. For many CNT applications it is of the foremost
      importance to know their frictional properties. However, very little is known
      about the frictional forces between an individual nanotube and a substrate or
      tip. Here, we present a combined theoretical and experimental study of the
      frictional forces encountered by a nanosize tip sliding on top of a supported
      multiwall CNT along a direction parallel or transverse to the CNT axis.
      Surprisingly, we find a higher friction coefficient in the transverse direction
      compared with the parallel direction. This behaviour is explained by a simulation
      showing that transverse friction elicits a soft 'hindered rolling' of the tube
      and a frictional dissipation that is absent, or partially absent for chiral CNTs,
      when the tip slides parallel to the CNT axis. Our findings can help in developing
      better strategies for large-scale CNT assembling and sorting on a surface.

PMID- 19749769
TI  - Giant magnetic-field-induced strains in polycrystalline Ni-Mn-Ga foams.
AB  - The magnetic shape-memory alloy Ni-Mn-Ga shows, in monocrystalline form, a
      reversible magnetic-field-induced strain (MFIS) up to 10%. This strain, which is
      produced by twin boundaries moving solely by internal stresses generated by
      magnetic anisotropy energy, can be used in actuators, sensors and energy
      harvesting devices. Compared with monocrystalline Ni-Mn-Ga, fine-grained Ni-Mn-Ga
      is much easier to process but shows near-zero MFIS because twin boundary motion
      is inhibited by constraints imposed by grain boundaries. Recently, we showed that
      partial removal of these constraints, by introducing pores with sizes similar to
      grains, resulted in MFIS values of 0.12% in polycrystalline Ni-Mn-Ga foams, close
      to those of the best commercial magnetostrictive materials. Here, we demonstrate
      that introducing pores smaller than the grain size further reduces constraints
      and markedly increases MFIS to 2.0-8.7%. These strains, which remain stable over
      >200,000 cycles, are much larger than those of any polycrystalline, active
      material.

PMID- 19749770
TI  - In vivo delivery of siRNA to immune cells by conjugation to a TLR9 agonist
      enhances antitumor immune responses.
AB  - Efficient delivery of small interfering (si)RNA to specific cell populations in
      vivo remains a formidable challenge to its successful therapeutic application. We
      show that siRNA synthetically linked to a CpG oligonucleotide agonist of toll
      like receptor (TLR)9 targets and silences genes in TLR9(+) myeloid cells and B
      cells, both of which are key components of the tumor microenvironment. When a CpG
      conjugated siRNA that targets the immune suppressor gene Stat3 is injected in
      mice either locally at the tumor site or intravenously, it enters tumor
      associated dendritic cells, macrophages and B cells. Silencing of Stat3 leads to
      activation of tumor-associated immune cells and ultimately to potent antitumor
      immune responses. Our findings demonstrate the potential of TLR agonist-siRNA
      conjugates for targeted gene silencing coupled with TLR stimulation and immune
      activation in the tumor microenvironment.

PMID- 19749771
TI  - Molecular signatures of disease brain endothelia provide new sites for CNS
      directed enzyme therapy.
AB  - The brain vasculature forms an immense network such that most neural cells are in
      contact with a microvessel. Here we tested the hypothesis that endothelia lining
      these vessels can be harnessed to create a cellular reservoir of enzyme
      replacement therapy to diseased brain. As a model system, we used mice with
      central nervous system (CNS) deficits due to lysosomal storage disease (LSD
      mice). The basic premise of this work is that recombinant enzyme expressed in,
      and secreted from, the vascular endothelia will be endocytosed by underlying
      neurons and glia, decreasing neuropathology. We screened a phage library in vivo
      by panning to identify peptides that bound the vascular endothelia in diseased
      and wild-type mice. Epitopes binding diseased brain were distinct from those
      panned from normal brain. Moreover, different epitopes were identified in two
      distinct LSD disease models, implying a unique vascular signature imparted by the
      disease state. Presentation of these epitopes on the capsid of adeno-associated
      virus (AAV) expanded the biodistribution of intravenously injected AAV from
      predominantly liver to include the CNS. Peripheral injection of the epitope
      modified AAVs expressing the enzymes lacking in LSD mice reconstituted enzyme
      activity throughout the brain and improved disease phenotypes in two distinct
      disease models.

PMID- 19749778
TI  - Vascular disease in psoriasis.

PMID- 19749772
TI  - Three-dimensional microscopy of the tumor microenvironment in vivo using optical
      frequency domain imaging.
AB  - Intravital multiphoton microscopy has provided powerful mechanistic insights into
      health and disease and has become a common instrument in the modern biological
      laboratory. The requisite high numerical aperture and exogenous contrast agents
      that enable multiphoton microscopy, however, limit the ability to investigate
      substantial tissue volumes or to probe dynamic changes repeatedly over prolonged
      periods. Here we introduce optical frequency domain imaging (OFDI) as an
      intravital microscopy that circumvents the technical limitations of multiphoton
      microscopy and, as a result, provides unprecedented access to previously
      unexplored, crucial aspects of tissue biology. Using unique OFDI-based approaches
      and entirely intrinsic mechanisms of contrast, we present rapid and repeated
      measurements of tumor angiogenesis, lymphangiogenesis, tissue viability and both
      vascular and cellular responses to therapy, thereby demonstrating the potential
      of OFDI to facilitate the exploration of physiological and pathological processes
      and the evaluation of treatment strategies.

PMID- 19749779
TI  - How to validate outcome instruments for pemphigus.
AB  - In this issue, Rosenbach et al. assess the reliability and validity of outcome
      instruments for pemphigus. Although the authors address the need for validated
      tools for use in therapeutic trials, the outcome instrument has been evaluated
      using data from only 15 selected pemphigus patients. Moreover, important steps in
      the validation process, such as sensitivity to change and construct validity, are
      not reported. Here, we discuss the methodological aspects of instrument
      assessment.

PMID- 19749780
TI  - Protein kinase Calpha puts the hand cuffs on epidermal keratinocyte
      proliferation.
AB  - As the predominant cellular receptor for phorbol esters, protein kinase C (PKC)
      is assumed to play a role in epidermal carcinogenesis. Nevertheless, determining
      its exact role in keratinocytes has been difficult because of the existence of
      multiple PKC isoforms and the inherent weaknesses in methodologies used to
      investigate their function. In this issue, Jerome-Morais et al. describe their
      use of multiple in vitro, in situ, overexpression, and knockdown approaches to
      demonstrate that PKCalpha induces keratinocyte growth arrest.

PMID- 19749781
TI  - Hydroxychloroquine induces autophagic cell death of human dermal fibroblasts:
      implications for treating fibrotic skin diseases.
AB  - Hydroxychloroquine (HCQ) is widely used to treat rheumatic and inflammatory
      diseases. It inhibits inflammation by downregulating the effects of inflammatory
      cells and their mediators. Although HCQ has been used to treat several fibrotic
      skin diseases, the mechanisms by which it exerts its effects on human dermal
      fibroblasts (HDFs) have not been studied in detail. In this issue, Ramser et al.
      show that HCQ inhibits proliferation of HDFs and induces autophagy. These
      observations are supported by the demonstration that HCQ upregulates Beclin-1, a
      key regulator of autophagy. Future studies are needed to determine whether HCQ
      induces autophagy in vivo and whether antimalarials have antifibrotic effects
      when used in clinically relevant doses.

PMID- 19749782
TI  - Nitric oxide-containing nanoparticles as an antimicrobial agent and enhancer of
      wound healing.
AB  - Nitric oxide (NO) is known to be involved in wound healing and to have
      antimicrobial actions. Developing a means of delivering a diatomic, gaseous free
      radical has been a technical challenge. Using a combination of techniques,
      Martinez and colleagues have developed an ingenious method of storing NO, and
      they demonstrate its efficacy in treating infected wounds.

PMID- 19749783
TI  - Spitting image: tick saliva assists the causative agent of Lyme disease in
      evading host skin's innate immune response.
AB  - Lyme disease is caused by the spirochete Borrelia burgdorferi and is transmitted
      through ticks. Inhibition of host skin's innate immune response might be
      instrumental to both tick feeding and B. burgdorferi transmission. The article by
      Marchal et al. describes how tick saliva suppresses B. burgdorferi-induced
      antimicrobial peptide production. This inhibition directly facilitates survival
      of the spirochete and might lead to diminished chemotaxis of leukocytes toward
      the site of the tick bite.

PMID- 19749785
TI  - Upregulation of human DNA binding protein A (dbpA) in gastric cancer cells.
AB  - AIM: To determine the effect of human DNA binding protein (dbpA) on the biology
      of gastric cancer cells. METHODS: DbpA expression was analyzed by Western blot
      analysis and immunofluorescence staining in gastric cancer tissues and cell
      lines. A dbpA-specific small interference (si) RNA was designed and synthesized.
      Suppressive effect of siRNA on dbpA expression was assessed by real-time RT-PCR.
      Transwell migration and colony formation assays were used to assess the
      inhibitory effects of dbpA siRNA on cell invasion and tumorigenesis in vitro.
      Drug-sensitivity was evaluated using a conventional 3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyl tetrazolium bromide (MTT) assay. RESULTS: The expression of dbpA was
      upregulated in gastric cancer tissues and cell lines as compared to adjacent
      normal tissues or gastric epithelial cells. siRNA treatment successfully silenced
      dbpA expression. Silencing of dbpA increased expression of E-cadherin, decreased
      expression of adenomatous polyposis coli (APC), beta-catenin and cyclin D1, but
      had no effect on expression of NF-kappaB. Silencing of dbpA also suppressed cell
      invasion and colony formation of SGC7901 cells, and enhanced their
      chemosensitivity to 5-fluorouracil. CONCLUSION: DbpA plays an important role in
      the pathogenesis and development of gastric cancer, and the process involves E
      cadherin, APC, beta-catenin and cyclin D1. Silencing of dbpA might be a novel
      therapeutic strategy for increasing chemosensitivity to 5-fluorouracil in gastric
      cancer.

PMID- 19749786
TI  - Increase in sphingolipid catabolic enzyme activity during aging.
AB  - AIM: To understand the contribution of sphingolipid metabolism and its
      metabolites to development and aging. METHODS: A systemic analysis on the changes
      in activity of sphingolipid metabolic enzymes in kidney, liver and brain tissues
      during development and aging was conducted. The study was conducted using tissues
      from 1-day-old to 720-day-old rats. RESULTS: Catabolic enzyme activities as well
      as the level of sphingomyelinase (SMase) and ceramidase (CDase) were higher than
      that of anabolic enzyme activities, sphingomyelin synthase and ceramide synthase.
      This suggested an accumulation of ceramide and sphingosine during development and
      aging. The liver showed the highest neutral-SMase activity among the tested
      enzymes while the kidney and brain exhibited higher neutral-SMase and ceramidase
      activities, indicating a high production of ceramide in liver and
      ceramide/sphingosine in the kidney and brain. The activities of sphingolipid
      metabolic enzymes were significantly elevated in all tested tissues during
      development and aging, although the onset of significant increase in activity
      varied on the tissue and enzyme type. During aging, 18 out of 21 enzyme
      activities were further increased on day 720 compared to day 180. CONCLUSION:
      Differential increases in sphingolipid metabolic enzyme activities suggest that
      sphingolipids including ceramide and sphingosine might play important and dynamic
      roles in proliferation, differentiation and apoptosis during development and
      aging.

PMID- 19749787
TI  - Hepatocyte growth factor protects endothelial cells against gamma ray irradiation
      induced damage.
AB  - AIM: To investigate the effect of HGF on proliferation, apoptosis and migratory
      ability of human vascular endothelial cells against gamma ray irradiation.
      METHODS: ECV304 cells derived from adult human umbilical vein endothelial cells
      (HUVEC) were irradiated with a single gamma ray dose of 20 Gy.
      Immunocytochemistry and Western blot analysis were used to detect c-Met protein
      expression and HGF/c-Met signal pathway. In the HGF-treated groups, ECV304 cells
      were incubated with HGF (20 or 40 ng/mL) 3 h prior to irradiation. At 48 h post
      irradiation, the proliferation of ECV304 cells was measured by MTT assay, the
      apoptosis was assessed by flow cytometry, and the migratory ability of ECV304
      cells was measured by transwell chamber assay. RESULTS: c-Met protein is
      expressed in ECV304 cells and can be activated by HGF. Gamma ray irradiation
      inhibits proliferation and migration of ECV304 cells in a dose-dependent manner.
      HGF significantly promoted the proliferation of ECV304 cells, and flow cytometry
      revealed that HGF can inhibit apoptosis of ECV304 cells. Transwell chamber assay
      also showed that HGF increases migration activity of endothelial cells.
      CONCLUSION: HGF may afford protection to vascular endothelial cells against gamma
      ray irradiation-induced damage.

PMID- 19749788
TI  - The impact of extracellular and intracellular Ca2+ on ethanol-induced smooth
      muscle contraction.
AB  - AIM: To evaluate the impact of extracellular and intracellular Ca2+ on
      contractions induced by ethanol in smooth muscle. METHODS: Longitudinal smooth
      muscle strips were prepared from the gastric fundi of mice. The contractions of
      smooth muscle strips were recorded with an isometric force displacement
      transducer. RESULTS: Ethanol (164 mmol/L) produced reproducible contractions in
      isolated gastric fundal strips of mice. Although lidocaine (50 and 100
      micromol/L), a local anesthetic agent, and hexamethonium (100 and 500
      micromol/L), a ganglionic blocking agent, failed to affect these contractions,
      verapamil (1-50 micromol/L) and nifedipine (1-50 micromol/L), selective blockers
      of L-type Ca2+ channels, significantly inhibited the contractile responses of
      ethanol. Using a Ca(2+)-free medium nearly eliminated these contractions in the
      same tissue. Ryanodine (1-50 micromol/L) and ruthenium red (10-100 micromol/L),
      selective blockers of intracellular Ca2+ channels/ryanodine receptors;
      cyclopiazonic acid (CPA; 1-10 mumol/L), a selective inhibitor of sarcoplasmic
      reticulum (SR) Ca(2+)-ATPase; and caffeine (0.5-5 mmol/L), a depleting agent of
      intracellular Ca2+ stores, significantly inhibited the contractile responses
      induced by ethanol. In addition, the combination of caffeine (5 mmol/L) plus CPA
      (10 micromol/L), and ryanodine (10 micromol/L) plus CPA (10 micromol/L), caused
      further inhibition of contractions in response to ethanol. This inhibition was
      significantly different from those associated with caffeine, ryanodine or CPA.
      Furthermore the combination of caffeine (5 mmol/L), ryanodine (10 micromol/L) and
      CPA(10 micromol/L) eliminated the contractions induced by ethanol in isolated
      gastric fundal strips of mice. CONCLUSION: Both extracellular and intracellular
      Ca2+ may have important roles in regulating contractions induced by ethanol in
      the mouse gastric fundus.

PMID- 19749789
TI  - Pannexin2 as a novel growth regulator in C6 glioma cells.
AB  - Connexins (Cxs), the gap junction proteins, have been found to be downregulated
      in many types of cancers including gliomas. By restoring gap junctional
      communication in cancer cell models, the neoplastic phenotype can be reversed,
      suggesting Cxs are tumor suppressors. Pannexin2 (Panx2) is a member of the novel
      gap junction protein family, Panxs, and it has been proposed as a brain-specific
      protein. Recently, gene array analysis showed an overall reduction of Panx2 in
      gliomas, and a direct correlation was observed between Panx2 expression and post
      diagnosis survival in patients. In this study, we explored the potential inverse
      correlation between Panx2 and glioma oncogenicity. A decrease or absence of Panx2
      expression in a panel of human glioma cell lines was found, whereas an
      appreciable amount of Panx2 was detected in both human brain and astrocytes.
      Stable Panx2 expression revealed a flattened morphology and increased cell-cell
      contacts in rat C6 glioma cells similar to Panx1. However, in contrast to Panx1
      and Panx3, Panx2 was predominately detected in the cytoplasm in vesicle-like
      patterns but not at the plasma membrane. Coexpression of Panx2 and Panx1 did not
      show colocalization of both Panxs. Strikingly, restoration of Panx2 expression
      significantly reduced in vitro oncogenicity parameters, including monolayer
      saturation density and anchorage-independent growth, as well as in vivo tumor
      growth. This study suggests a role of aberrant Panx2 expression during
      gliomagenesis, and that Panx2 independently functions as a negative growth
      regulator without Panx1.

PMID- 19749791
TI  - Repression of SHP-1 expression by p53 leads to trkA tyrosine phosphorylation and
      suppression of breast cancer cell proliferation.
AB  - The nerve growth factor (NGF) receptor, trkA, the tumour suppressor p53 and the
      phosphatase SHP-1 are critical in cell proliferation and differentiation. SHP-1
      is a trkA phosphatase that dephosphorylates trkA at tyrosines (Y) 674 and 675.
      p53 can induce trkA activation and tyrosine phosphorylation in the absence of NGF
      stimulation. In breast cancer tumours trkA expression is associated with
      increased patient survival. TrkA protein expression is higher in breast-cancer
      cell lines than in normal breast epithelia. In cell lines (but not in normal
      breast epithelia) trkA is functional and can be NGF-stimulated to promote cell
      proliferation. This study investigates the functional relationship between trkA,
      p53 and SHP-1 in breast-cancer, and reveals that in wild-type (wt) trkA
      expressing breast-cancer cells both endogenous wtp53, activated by therapeutic
      agents, and transfected wtp53 repress expression of SHP-1 through the proximal
      CCAAT sequence of the SHP-1-P1-promoter and the transcription factor NF-Y. In
      these cells trkA-Y674/Y675 phosphorylation is detected when SHP-1 protein levels
      decrease in a wtp53-dependent manner. Proliferation and cell-cycle assays, with
      cells expressing endogenous or transfected wt-trkA and a temperature-sensitive
      p53 grown at 32 degrees C (when p53 is in the wt configuration), show suppressed
      cell proliferation. Suppression is not detected when grown at 37 degrees C (when
      p53 is in the mutant configuration). A release from suppression is observed when
      these cells are transiently transfected with wt-SHP-1 and grown at 32 degrees C.
      Suppression is also detected when, as control, wt-trkA-expressing cells are
      transiently transfected with SHP-1-siRNA, but not when a dominant-negative (DN)
      mutant trkA is used to abolish wt-trkA activity. Importantly, suppression is not
      seen with control trkA-negative breast-cancer cells (expressing wtp53, wt-SHP-1
      and undetectable trkA), transfected with Y674F/Y675F mutant-trkA. BrdU
      incorporation experiments reveal lack of incorporation in cells expressing wt
      trkA and wtp53, or wt-trkA and SHP-1-siRNA. However, BrdU is incorporated in the
      presence of Y674F/Y675F mutant trkA or DN mutant trkA. These results indicate
      that p53 repression of SHP-1 expression leads to trkA-Y674/Y675 phosphorylation
      and trkA-dependent suppression of breast-cancer cell proliferation. These data
      provide an explanation as to why high trkA levels are associated with favourable
      prognosis.

PMID- 19749790
TI  - Mutant fibroblast growth factor receptor 3 induces intracellular signaling and
      cellular transformation in a cell type- and mutation-specific manner.
AB  - Although activating mutations of fibroblast growth factor receptor 3 (FGFR3) are
      frequent in bladder tumors, little information is available on their specific
      effects in urothelial cells or the basis for the observed mutation spectrum. We
      investigated the phenotypic and signaling consequences of three FGFR3 mutations
      (S249C, Y375C, and K652E) in immortalized normal human urothelial cells (TERT
      NHUC) and mouse fibroblasts (NIH-3T3). In TERT-NHUC, all mutant forms of FGFR3
      induced phosphorylation of FRS2alpha and ERK1/2, but not AKT or SRC. PLCgamma1
      phosphorylation was only observed in TERT-NHUC expressing the common S249C and
      Y375C mutations, and not the rare K652E mutation. Cells expressing S249C and
      Y375C FGFR3 displayed an increased saturation density, related to increased
      proliferation and viability. This effect was significantly dependent on PLCgamma1
      signaling and undetectable in cells expressing K652E FGFR3, which failed to
      phosphorylate PLCgamma1. In contrast to TERT-NHUC, expression of mutant FGFR3 in
      NIH-3T3 resulted in phosphorylation of Src and Akt. In addition, all forms of
      mutant FGFR3 were able to phosphorylate Plcgamma1 and induce morphological
      transformation, cell proliferation, and anchorage-independent growth. Our results
      indicate that the effects of mutant FGFR3 are both cell type specific and
      mutation specific. Mutant FGFR3 may confer a selective advantage in the
      urothelium by overcoming normal contact inhibition of proliferation.

PMID- 19749792
TI  - A Wnt kinase network alters nuclear localization of TCF-1 in colon cancer.
AB  - Constitutive activation of the Wnt/beta-catenin pathway has been implicated as
      the primary cause of colon cancer. However, the major transducers of Wnt
      signaling in the intestine, T-cell factor 1 (TCF-1) and TCF-4, have opposing
      functions. Knockout of TCF-4 suppresses growth and maintenance of crypt stem
      cells, whereas knockout of TCF-1 leads to adenomas. These phenotypes suggest that
      TCF-4 is Wnt-promoting, whereas TCF-1 acts like a tumor suppressor. Our study of
      TCF expression in human colon crypts reveals a mechanistic basis for this
      paradox. In normal colon cells, a dominant-negative isoform of TCF-1 (dnTCF-1) is
      expressed that is equally distributed between nuclear and cytoplasmic
      compartments. In colon cancer cells, TCF-1 is predominantly cytoplasmic.
      Localization is because of active nuclear export and is directed by an autocrine
      acting Wnt ligand that requires Ca2+/calmodulin-dependent kinase II (CaMKII)
      activity for secretion and a downstream step in the export pathway. TCF-4 remains
      nuclear; its unopposed activity is accompanied by downregulation of dnTCF-1 and
      increased expression of full-length isoforms. Thus, the dnTCF-1 and TCF-4 balance
      is corrupted in cancer by two mechanisms, a Wnt/CaMKII kinase signal for nuclear
      export and decreased dnTCF-1 expression. We propose that dnTCF-1 provides
      homeostatic regulation of Wnt signaling and growth in normal colon, and the
      alterations in nuclear export and promoter usage contribute to aberrant Wnt
      activity in colon cancer.

PMID- 19749793
TI  - Hsp70 molecular chaperones are required to support p53 tumor suppressor activity
      under stress conditions.
AB  - p53 as an unstable protein in vitro likely requires stabilizing factors to act as
      a tumor suppressor in vivo. Here, we show that in human cells transfected with
      wild-type (WT) p53, Hsp90 and Hsp70 molecular chaperones maintain the p53 native
      conformation under heat-shock conditions (42 degrees C) as well as assist p53
      refolding at 37 degrees C, during the recovery from heat shock. We also show that
      the interaction of WT p53 with WAF1 promoter in cells is sensitive to Hsp70 and
      Hsp90 inhibition already at 37 degrees C and further decreased on heat shock. The
      influence of chaperones on p53 binding to the WAF1 promoter sequence has been
      confirmed in vitro, using highly purified proteins. Hsp90 stabilizes the binding
      of p53 to the promoter sequence at 37 degrees C, whereas under heat-shock
      conditions the requirement for the Hsp70-Hsp40 system and its cooperation with
      Hsp90 increases. Hop co-chaperone additionally stimulates these reactions.
      Interestingly, the combined Hsp90 and Hsp70-Hsp40 allow for a limited in vitro
      restoration of the DNA-binding activity by the p53 oncogenic variant R249S and
      affect its conformation in cells. Our results indicate for the first time that,
      especially under stress conditions, not only Hsp90 but also Hsp70 is required for
      the chaperoning of WT and R249S p53.

PMID- 19749794
TI  - Pro-proliferative FoxM1 is a target of p53-mediated repression.
AB  - The p53 tumor suppressor protein acts as a transcription factor to modulate
      cellular responses to a wide variety of stresses. In this study we show that p53
      is required for the downregulation of FoxM1, an essential transcription factor
      that regulates many G2/M-specific genes and is overexpressed in a multitude of
      solid tumors. After DNA damage, p53 facilitates the repression of FoxM1 mRNA,
      which is accompanied by a decrease in FoxM1 protein levels. In cells with reduced
      p53 expression, FoxM1 is upregulated after DNA damage. Nutlin, a small-molecule
      activator of p53, suppresses FoxM1 levels in two cell lines in which DNA damage
      facilitates only mild repression. Mechanistically, p53-mediated inhibition of
      FoxM1 is partially p21 and retinoblastoma (Rb) family dependent, although in some
      cases p21-independent repression of FoxM1 was also observed. The importance of
      FoxM1 to cell fate was indicated by the observation that G2/M arrest follows
      FoxM1 ablation. Finally, our results indicate a potential contribution of p53
      mediated repression of FoxM1 for maintenance of a stable G2 arrest.

PMID- 19749795
TI  - PU.1 induces apoptosis in myeloma cells through direct transactivation of TRAIL.
AB  - We earlier reported that PU.1 was downregulated in myeloma cell lines and myeloma
      cells in a subset of myeloma patients, and that conditional PU.1 expression in
      PU.1-negative myeloma cell lines, U266 and KMS12PE, induced growth arrest and
      apoptosis. To elucidate the molecular mechanisms of the growth arrest and
      apoptosis, we performed DNA microarray analyses to compare the difference in gene
      expression before and after PU.1 induction in U266 cells. Among cell cycle
      related genes, cyclin A2, cyclin B1, CDK2 and CDK4 were downregulated and p21 was
      upregulated, although among apoptosis-related genes, tumor necrosis factor (TNF)
      related apoptosis inducing ligand (TRAIL) was found highly upregulated. When
      TRAIL was knocked down by small interference RNAs, apoptosis of PU-1-expressing
      cells was inhibited, suggesting that TRAIL has a critical role in PU.1-induced
      apoptosis in both U266 and KMS12PE myeloma cells. In both U266 and KMS12PE cells
      expressing PU.1, PU.1 directly bound to a region 30 bp downstream of the
      transcription start site of the TRAIL gene. Upregulation of PU.1-induced
      transactivation of the TRAIL promoter in reporter assays, and disruption of the
      PU.1-binding site in the TRAIL promoter eliminated this transactivation.
      Therefore, we conclude that PU.1 is capable of inducing apoptosis in certain
      myeloma cells by direct transactivation of TRAIL.

PMID- 19749796
TI  - Suppression of lung adenocarcinoma through menin and polycomb gene-mediated
      repression of growth factor pleiotrophin.
AB  - Menin upregulates transcription of cell-cycle inhibitors to suppress endocrine
      tumors, but it is poorly understood how menin suppresses non-endocrine tumors
      such as lung cancer. Here, we show that menin inhibits proliferation of human
      lung cancer cells and growth of lung cancer in mice. The menin-mediated tumor
      suppression requires repression of growth factor pleiotrophin (PTN), which binds
      to its cell surface receptor, anaplastic lymphoma kinase (ALK) that is activated
      in certain lung adenocarcinomas. Menin represses PTN transcription and PTN
      induced proliferation of human lung cancer cells, and menin expression is
      substantially reduced in primary human lung adenocarcinomas. Notably, menin binds
      the PTN locus and enhances Polycomb gene Enhancer of Zeste homolog 2 (EZH2)
      mediated histone H3 lysine 27 trimethylation (H3K27m3), a negative mark for gene
      transcription but does not affect histone H3K4 methylation that is usually
      upregulated by menin in endocrine cells. Together, our findings indicate that
      menin suppresses lung cancer partly through increasing Polycomb gene-mediated
      H3K27 methylation and repressing PTN transcription, unraveling a novel,
      epigenetically regulated PTN-ALK signaling pathway in suppressing lung cancer.

PMID- 19749797
TI  - Thyroid hormone receptor mutants implicated in human hepatocellular carcinoma
      display an altered target gene repertoire.
AB  - Thyroid hormone receptors (TRs) are hormone-regulated transcription factors that
      control multiple aspects of normal physiology and development. Mutations in TRs
      have been identified at high frequency in certain cancers, including human
      hepatocellular carcinomas (HCCs). The majority of HCC-TR mutants bear lesions
      within their DNA recognition domains, and we have hypothesized that these lesions
      change the mutant receptors' target gene repertoire in a way crucial to their
      function as oncoproteins. Using stable cell transformants and expression array
      analysis, we determined that mutant TRs isolated from two different HCCs do, as
      hypothesized, display a target gene repertoire distinct from that of their normal
      TR progenitors. Only a subset of genes regulated by wild-type TRs was regulated
      by the corresponding HCC-TR mutants. More surprisingly, the HCC-TR mutants also
      gained the ability to regulate additional target genes not recognized by the wild
      type receptors, and were not simply restricted to repression, but could also
      activate a subset of their target genes. We conclude that the TR mutants isolated
      from HCC have sustained multiple alterations from their normal progenitors that
      include not only changes in their transcriptional outputs, but also changes in
      the genes they target; both are likely to contribute to neoplasia.

PMID- 19749798
TI  - Synergistic proapoptotic effects of the two tyrosine kinase inhibitors pazopanib
      and lapatinib on multiple carcinoma cell lines.
AB  - Pazopanib and lapatinib are two tyrosine kinase inhibitors that have been
      designed to inhibit the VEGF tyrosine kinase receptors 1, 2 and 3 (pazopanib),
      and the HER1 and HER2 receptors in a dual manner (lapatinib). Pazopanib has also
      been reported to mediate inhibitory effect on a selected panel of additional
      tyrosine kinases such as PDGFR and c-kit. Here, we report that pazopanib and
      lapatinib act synergistically to induce apoptosis of A549 non-small-cell lung
      cancer cells. Systematic assessment of the kinome revealed that both pazopanib
      and lapatinib inhibited dozens of different tyrosine kinases and that their
      combination could suppress the activity of some tyrosine kinases (such as c-Met)
      that were not or only partially affected by either of the two agents alone. We
      also found that pazopanib and lapatinib induced selective changes in the
      transcriptome of A549 cells, some of which were specific for the combination of
      both agents. Analysis of a panel of unrelated human carcinoma cell lines revealed
      a signature of 52 genes whose up- or downregulation reflected the combined action
      of pazopanib and lapatinib. Indeed, pazopanib and lapatinib exerted synergistic
      cytotoxic effects on several distinct non-small-cell lung cancer cells as well as
      on unrelated carcinomas. Altogether, these results support the contention that
      combinations of tyrosine kinase inhibitors should be evaluated for synergistic
      antitumor effects. Such combinations may lead to a 'collapse' of pro-survival
      signal transduction pathways that leads to apoptotic cell death.

PMID- 19749799
TI  - PIM1 phosphorylates and negatively regulates ASK1-mediated apoptosis.
AB  - The serine/threonine kinase, PIM1, is involved in promoting cell survival in part
      by phosphorylation and inhibition of proapoptotic proteins. Apoptosis signaling
      kinase 1 (ASK1), a mitogen-activated protein kinase kinase kinase, is involved in
      the so-called stress-activated pathways that contribute to apoptotic cell death.
      Here we show that PIM1 phosphorylates ASK1 specifically on serine residue 83
      (Ser83) both in vitro and in vivo and that PIM1 binds to ASK1 in cells by co
      immunoprecipitation. Using H1299 cells, our results further demonstrate that PIM1
      phosphorylation of ASK1 decreases its kinase activity induced by oxidative
      stress. PIM1 phosphorylation of ASK1 on Ser83 inhibited ASK1-mediated c-Jun N
      terminal kinase phosphorylation as well as p38 kinase phosphorylation. Under
      H(2)O(2)-induced stress conditions that normally lead to apoptosis, these
      phosphorylation events were associated with inhibition of caspase-3 activation
      and resulted in reduced cell death. Moreover, knockdown of PIM1 in H1299 cells
      decreased phosphorylation of endogenous Ser83 of ASK1 and was associated with a
      decrease in cell viability after H(2)O(2) treatment. Taken together, these data
      reveal a novel mechanism by which PIM1 promotes cell survival that involves
      negative regulation of the stress-activated kinase, ASK1.

PMID- 19749800
TI  - A restricted signature of miRNAs distinguishes APL blasts from normal
      promyelocytes.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs involved in the regulation of
      critical cell processes such as apoptosis, cell proliferation and
      differentiation. A small set of miRNAs is differentially expressed in
      hematopoietic cells and seemingly has an important role in granulopoiesis and
      lineage differentiation. In this study, we analysed, using a quantitative real
      time PCR approach, the expression of 12 granulocytic differentiation signature
      miRNAs in a cohort of acute promyelocytic leukemia (APL) patients. We found nine
      miRNAs overexpressed and three miRNAs (miR-107, -342 and let-7c) downregulated in
      APL blasts as compared with normal promyelocytes differentiated in vitro from
      CD34+ progenitors. Patients successfully treated with all-trans-retinoic acid
      (ATRA) and chemotherapy showed downregulation of miR-181b and upregulation of miR
      15b, -16, -107, -223, -342 and let-7c. We further investigated whether the APL
      associated oncogene, promyelocytic leukemia gene (PML)/retinoic acid receptor
      alpha (RARalpha), might be involved in the transcriptional repression of miR-107,
      -342 and let-7c. We found that PML/RARalpha binds the regulatory sequences of the
      intragenic miR-342 and let-7c. In addition, we observed, in response to ATRA, the
      release of PML/RARalpha paralleled by their transcriptional activation, together
      with their host genes, EVL and C21orf34alpha. In conclusion, we show that a small
      subset of miRNAs is differentially expressed in APL and modulated by ATRA-based
      treatment.

PMID- 19749801
TI  - Functional performance status of hematopoietic SCT recipients in the sub-acute
      phase of recovery.
AB  - This study assessed the functional capacity of sub-acute SCT recipients using
      validated physical performance tests, including 6-min walk distance, repeated sit
      to-stand time and 50-ft walk time, and compared these outcomes with those
      reported for a heterogeneous oncology population. The medical records of 80
      consecutive sub-acute SCT recipients not receiving corticosteroids were
      retrospectively reviewed for demographic, medical and anthropometric information,
      and outcomes for these physical performance tests administered at the time of
      initial physiotherapy evaluation. Measures of central tendency, 95% confidence
      intervals, unpaired t-tests and correlation coefficients were calculated using a
      SPSS statistical package. SCT recipients completed the 50-ft walk in 10.66+/-4.43
      s, repeated sit-to-stand trial in 4.16+/-1.82 s and walked 400.2 m in 6 min. For
      the timed tests, SCT recipients were approximately twice as fast as a
      heterogeneous group of oncology patients and walked approximately 50% further in
      6 min. No overlap in the 95% confidence intervals for the two groups was observed
      for any of the tests. These results (1) suggest that reference values describing
      the functional capacity of a heterogeneous oncology population underestimate the
      functional capacity of SCT recipients and (2) provide clinically useful reference
      values for assessing functional capacity of sub-acute SCT recipients referred for
      physiotherapy.

PMID- 19749803
TI  - Speckle processing method for synthetic-aperture-radar phase correction.
AB  - Uncompensated phase errors present in synthetic-aperture-radar data can have a
      disastrous effect on reconstructed image quality. We present a new iterative
      algorithm that holds promise of being a robust estimator and corrector for
      arbitrary phase errors. Our algorithm is similar in many respects to speckle
      processing methods currently used in optical astronomy. We demonstrate its
      ability to focus scenes containing large amounts of phase error regardless of the
      phase-error structure or its source. The algorithm works extremely well in both
      high and low signal-to-clutter conditions without human intervention.

PMID- 19749804
TI  - Dual optimality of the phase-only filter.
AB  - A measure of the peak-to-sidelobe performance for correlation filters is defined.
      The phase-only filter is then shown to be optimum with respect to the peak-to
      sidelobe criterion. The phase-only filter has been previously shown to give
      optimum signal-to-noise performance. Thus, under the assumption of a unit modulus
      phase device, optimum peak-to-sidelobe and signal-to-noise performance can be
      obtained simultaneously.

PMID- 19749805
TI  - Procedure for recording multiple-exposure holograms with equal diffraction
      efficiency in photorefractive media.
AB  - We report experimental results that demonstrate for the first time, to our
      knowledge, more than 20 holograms stored and recalled with equal diffraction
      efficiency in photorefractive LiNbO(3). A physical explanation for this new
      recording procedure is presented, and a comparison is made with previous exposure
      methods that shows an order-of-magnitude increase in diffraction efficiency with
      the order of exposure for optically erasable holograms. The procedure holds for
      recording times much less than the saturation exposure time.

PMID- 19749806
TI  - Spatially resolved flow velocity measurements using laser-induced fluorescence
      from a pulsed laser.
AB  - We describe how spatially resolved velocity measurements can be acquired using a
      pulse-amplified single-mode cw laser with a potential of single-shot
      measurements. The laser beam was tuned to the point of maximum slope of a Doppler
      broadened absorption profile of I(2), which was seeded into the flow. The beam
      was then split into two components and sent counterpropagating through the
      measurement region. By diode-array detection of the laserinduced fluorescence
      from I(2), spatially and temporally resolved velocities can be acquired.

PMID- 19749807
TI  - Doppler-free laser-induced fluorescence of oxygen atoms in an atmospheric
      pressure flame.
AB  - Doppler-free laser-induced fluorescence of oxygen atoms has been measured in the
      burnt gases of an atmospheric-pressure flame, where the Doppler and collisional
      widths are similar. The 3p(3)P level was excited using counterpropagating beams
      at 226 nm. Upper-state fine-structure splitting could be partially resolved, and
      a collisionally broadened Lorentzian width of 0.42 cm(-1) was measured. This
      corresponds to a broadening cross section of 10(-13) cm(2), which is larger than
      that expected for collisional quenching alone.

PMID- 19749808
TI  - Saturation of three-photon ionization of atomic hydrogen and deuterium at 243 nm.
AB  - Two-photon-resonant, three-photon ionization of atomic hydrogen and deuterium is
      performed at 243 nm, and the ions are detected by time-of-flight mass
      spectrometry. The power dependence of the 1S-2S two-photon excitation and one
      photon ionization of 2S hydrogen and deuterium are determined. The ionization
      step saturates at 4 x 10(6) W/cm(2). The two-photon step-power dependence varies
      with laser linewidth, with saturation occurring between 1 x 10(7) and 3 x 10(7)
      W/cm(2). The extraction electric field in the mass spectrometer does not affect
      the 2S excitation. Strong signals are recorded at atomic concentrations of 10(5)
      atoms/cm(3). Nonresonant ionization of background gases producing H(+) and D(+)
      is minimized.

PMID- 19749809
TI  - Simple efficient travelin-wave excitation of short-wavelength lasers using a
      conical pumping geometry.
AB  - A conically shaped pumping geometry can produce an efficient burst of laser
      radiation, without the need for an optical cavity, by restricting amplified
      spontaneous emission losses to a small region near the apex of the cone.
      Requirements on the active medium and on the size and intensity of the pumping
      source to make such a burst laser are derived. We calculate that a 15-mJ pulse of
      energy at 37.2 nm at an efficiency of 0.15% can be extracted from sodium vapor
      photoionized with radiation from a 1.06-microm-laser-produced plasma using this
      pumping geometry.

PMID- 19749810
TI  - Single-longitudinal-mode, tunable, pulsed Ti:sapphire laser oscillator.
AB  - A 2.0-mJ/pulse, 2-nsec, single-longitudinal-mode Ti:sapphire laser oscillator has
      been demonstrated in a compact grazing-incidence cavity configuration similar to
      a Littman arrangement. The oscillator's output beam quality is TEM(00), making it
      attractive for doubling and mixing applications. With currently available optics
      the laser is tunable over greater than 2500 cm(-1) from 746 to 918 nm.

PMID- 19749811
TI  - Single-frequency microchip Nd lasers.
AB  - Optically pumped, single-frequency, Nd-doped, solid-state lasers have been
      constructed using flat-flat cavities, which were diced from large dielectrically
      coated wafers of various crystals. For example, a Nd:YAG laser with a cavity
      length of 730 microm has operated at room temperature in a single longitudinal
      mode from a threshold of less than 1 mW to greater than 40 times the threshold.
      Theslope efficiency was greater than 30%. Heterodyne measurements showed an
      instrument-limited linewidth of 5 kHz. The microchip lasers demonstrate ways to
      reduce greatly the cost and complexity offabricating small lasers and electro
      optic devices.

PMID- 19749812
TI  - High-power diode-array-pumped frequency-doubled cw Nd:YAG laser.
AB  - We report the demonstration of a diode-array-pumped Nd:YAG laser with a cw output
      of 3.3 W at 1.06 microm. The laser was side pumped using linear diode arrays
      focused with cylindrical optics to provide efficient spatial overlap between the
      pump and cavity modes. Intracavity doubling using KTP produced 0.76-W output
      repetitively Q switched at 532 nm. The electrical efficiency for the 1.06-microm
      output was 3.5%.

PMID- 19749813
TI  - Network model for two-dimensional coupled laser arrays.
AB  - We have developed a network model for two-dimensional phase-locked arrays of
      coupled lasers that provides a basis for modeling arrays incorporating mixed
      coupling schemes. With this network approach we show that the modes of two
      dimensional arrays that are evanescently coupled in the lateral direction and
      injection coupled in the longitudinal direction can be expressed in terms of the
      eigenvalues of matrices separately representing the lateral and longitudinal
      coupling. As an example, the modes and grating-coupled near-field patterns of a 3
      x 3 array injection coupled through surface-emitting second-order Bragg
      reflectors are determined explicitly.

PMID- 19749814
TI  - Interferometric power amplifiers.
AB  - A general method of producing multielement amplifiers having a single output beam
      is described. The basic building blocks for these are either Michelson
      interferometers or Mach-Zehnder interferometers modified by the inclusion of gain
      in at least one arm of the interferometer. Demonstration of these multielement
      interferometric power amplifiers using broad-area AlGaAs gain elements and a
      single-mode AlGaAs master oscillator is described.

PMID- 19749815
TI  - Multipass dye-cell amplifier for high-repetition-rate femtosecond optical pulses.
AB  - We describe a dye-cell amplifier pumped by a copper-vapor laser at a 8.4-kHz
      repetition rate. This system avoids possible problems and restrictions arising
      from nozzle performance in commonly used jet-stream amplifiers. We obtained a
      nearly diffraction-limited beam with pulses of 60 fsec and energies of up to 50
      microJ.

PMID- 19749816
TI  - Enhanced mode locking of color-center lasers.
AB  - A significant enhancement in the mode locking of a KCl:Tl color-center laser has
      been observed when a length of optical fiber having positive group-velocity
      dispersion was incorporated within an external control cavity. Pulse durations of
      ~260 fsec were obtained by this method, representing a compression factor ~60x
      that with the colorcenter laser alone. Similar results have also been observed
      with an InGaAsP semiconductor diode amplifier as the nonlinear element within the
      control cavity.

PMID- 19749817
TI  - Design and performance of a high-power, synchronized Nd:YAG-dye laser system.
AB  - The design and performance of a Nd:YAG-dye-laser system capable of producing
      synchronized peak powers approaching 10 GW is described. The output of the
      amplified dye-laser system is several millijoules with fully tunable pulses as
      short as 300 fsec and is optically synchronized with the 3-GW output of an
      amplified Nd:YAG laser system, permitting a new class of high-intensity pump
      probe experiments. By using short ( approximately 70-psec) pulses to pump the dye
      amplifier, the energy of amplified spontaneous emission is reduced to less than
      10(-5) of that contained in the main subpicosecond pulse.

PMID- 19749818
TI  - Group-velocity-dispersion compensation of a passively mode-locked ring
      LiF:F(2)(+) color-center laser.
AB  - By using an intracavity prism sequence to control group-velocity dispersion,
      pulses as short as 180 fsec have been generated near 850 nm from a passively mode
      locked, traveling-wave LiF:F(2)(+) color-center laser.

PMID- 19749819
TI  - Femtosecond pulse generation in a laser with a nonlinear external resonator.
AB  - A simple model is presented to describe mode locking in a laser coupled to a
      nonlinear resonator. It reveals a new mechanism for pulse shortening and shows
      that shortening does not rely on dispersion in the auxiliary cavity. Experimental
      results are given to support the basic predictions of the model.

PMID- 19749820
TI  - Methods of passive and active mode locking using intracavity optical frequency
      mixing.
AB  - The mode-locking technique based on intracavity second-harmonic generation is
      extended to sum- and difference-frequency generation. Simultaneous passive mode
      locking of two different types of laser in a combined cavity is thus possible. By
      using the same principle, a laser may be actively mode locked by injection of a
      pulse train from another mode-locked laser.

PMID- 19749821
TI  - Four-wave mixing with dynamic Stark effects in flames.
AB  - Four-wave mixing is studied in a Na-seeded flame in the regime of strong
      saturation of the Na D-line transitions. The output frequency differs from that
      of the input lasers so that spectral discrimination can distinguish the mixing
      signal. Scans of the D2 resonance with another laser set at the D1-line resonance
      reveals two resonances corresponding to the D2 resonance and the frequency
      difference of the D levels. The mixing efficiency at the D2 resonance increases
      with the detuning of the D1 resonance. The frequency difference resonance is weak
      because of interference between multiple coherent pathways.

PMID- 19749822
TI  - Dispersion in the anisotropy of optical third-harmonic generation in silicon.
AB  - We present what are to our knowledge the first theoretical and experimental
      results for dispersion in the anisotropy (sigma) of chi?((3)) associated with
      optical third-harmonic generation in Si. The theory is based on a full empirical
      tight binding band-structure calculation, and the results agree well with our
      measurements for 0.72 microm < lambda < 1.9 microm. The calculated low-frequency
      limit of sigma agrees with measurements from the literature better than earlier
      calculations do. In addition, the dispersion in the relative phase of
      chi1212((3))/chi1111((3)) also shows good agreement with experiment.

PMID- 19749823
TI  - Ultraviolet continuous-wave phase conjugation at 285 nm.
AB  - Phase conjugation by degenerate four-wave mixing has been performed with a cw UV
      source on the Mg I resonance line at 285 nm ((1)S(0)-(1)P(1)(0)). Experimental
      observations and a comparison with a simple reflectivity model are presented.

PMID- 19749824
TI  - Observation of pressure-induced nonreciprocity in a ring four-wave-mixing
      oscillator: application to optical gyros.
AB  - We have studied the four-wave-mixing oscillation obtained when a cell containing
      sodium and a buffer gas is enclosed in a ring cavity. The beat frequency Deltanu
      between the two counterrotating beams is shown to depend on the intensity
      difference (I(1) - I(2)) between the two pump beams. The curve giving Deltanu as
      a function of (I(1) - I(2)) is a gyrotype curve, which suggests some possible
      application for optical gyros.

PMID- 19749825
TI  - Monolithic MgO:LiNbO(3) doubly resonant optical parametric oscillator pumped by a
      frequency-doubled diode-laser-pumped Nd:YAG laser.
AB  - We have demonstrated a monolithic MgO:LiNbO(3) doubly resonant optical parametric
      oscillator (OPO) using an allsolid- state pump. The pump laser was a single-axial
      mode monolithic Nd:YAG nonplanar ring oscillator whose diode-laser pump was
      modulated at 325 kHz to produce relaxation oscillation spikes to higher peak
      powers at 1.06 microm that were frequency doubled in a resonant cavity to 532 nm.
      Pump depletions for the OPO of greater than 60% were observed when pumping six
      times above the calculated 40-mW threshold. The OPO output was temperature tuned
      from 1.01 to 1.13 microm, producing single-axial-mode output over much of the
      range. By changing the voltage applied across the OPO, the output wavelength was
      scanned as much as 11 nm in 310 V.

PMID- 19749826
TI  - Adaptive phase compensation in a Raman look-through configuration.
AB  - Raman look through is a technique for extending the use of low-power adaptive
      optics to the control of high-power laser beams. This is done by incorporating a
      Raman amplifier into an adaptive-optics system. We report the results of a Raman
      look-through experiment, which is to our knowledge the first demonstration of
      this technique.

PMID- 19749827
TI  - Pitchfork bifurcation and all-optical digital signal processing with a coupled
      element bistable system.
AB  - An optical bistable system composed of coupled nonlinear elements is proposed.
      This system features optical bistability without hysteresis, which appears
      through pitchfork bifurcation. It is shown theoretically that a flipflop
      operation and a complete set of logic-gate characteristics can be achieved easily
      on an all-optical basis.

PMID- 19749828
TI  - Bifurcation of scattering orders in degenerate four-wave mixing.
AB  - Novel bifurcating scattering orders are predicted for the Raman-Nath regime of
      degenerate four-wave mixing in a medium that displays optical bistability due to
      increasing absorption.

PMID- 19749829
TI  - Near-infrared four-wave mixing with gain and self-starting oscillators with
      photorefractive GaAs.
AB  - We report high-reflectivity four-wave mixing in photorefractive GaAs:Cr crystals
      at 1.06 microm using a nearly degenerate interaction with an externally applied
      dc electric field (moving-grating recording mode). The highest reflectivities (R
      approximately 5) are observed for the positive-readout configuration with cross
      polarized pump beams. The variation in reflectivity with the pump-beam ratio is
      presented for two pump-beam polarization states and compared with theory. Self
      starting optical resonators are also described.

PMID- 19749830
TI  - Energy transfer between injection-locked single-mode diode lasers by two-beam
      coupling in BaTiO(3).
AB  - Two-beam coupling in photorefractive BaTiO(3) is used to combine beams coherently
      from two injection-locked single-mode diode lasers operating at 830 nm. We are
      able to transfer more than 70% of the power in one beam to the other beam with
      this method.

PMID- 19749831
TI  - Interaction of optical solitons with a forward Raman pump wave.
AB  - The interaction between optical solitons and a forward Raman pump wave in fibers
      is investigated. It is found that when their relative velocity is small and the
      soliton pulse width is short, the soliton frequency is shifted by the
      interaction. Near zero relative velocity the pulse shape is distorted, in
      addition to having a frequency shift.

PMID- 19749832
TI  - Four-photon parametric mixing in optical fibers: effect of pump depletion.
AB  - The analytical solutions to differential equations governing nonlinear four
      photon mixing in optical fibers are presented for the general case of depleted
      pump power. The expressions reduce to those derived earlier with the assumption
      of nondepleted pump power. We find that the maximum power available for
      conversion from the pump waves to the signal waves resulting from a third-order
      nonlinearity depends on the index mismatch and that the index mismatch required
      for achieving maximum possible power transfer is a function of the frequency
      shift.

PMID- 19749833
TI  - Vector coupled-mode analysis of coupling between two identical optical fiber
      cores.
AB  - The vector coupled-mode analysis considering the exact HE(11) modes is applied to
      two single-mode coupled optical fiber cores, including the strongly guiding
      fibers. The accuracy of the conventional coupled-mode theory and the recently
      formulated new theory as applied to the two-core system is examined. Array modes
      of different polarization states are considered. It is shown that the full-wave
      coupled-mode calculations behave well in predicting the array-mode propagation
      constants beyond the weakly guiding regime and that the simpler conventional
      theory can provide satisfactory results when applied in the vectorial form.

PMID- 19749834
TI  - Cross talk in a fiber-optic Fabry-Perot sensor array with ring reflectors.
AB  - We demonstrate a fiber-optic interferometric sensor array based on the in-line
      Fabry-Perot configuration, which uses fiber ring reflectors to effect the low
      reflectivity elements required between each sensor section. The intrinsic optical
      cross talk that occurs between the sensor sections owing to multiple reflections
      is analyzed and compared with experimental results obtained with a four-sensor
      system.

PMID- 19749835
TI  - Method for propagation of total fields or beams through optical waveguides.
AB  - A new method for solving the scalar Helmholtz equation to obtain the propagation
      of total fields or beams through general optical waveguiding structures is
      presented. The method is based on converting the partial differential equation
      into a matrix total differential equation using a collocation method and then
      solving the resulting equation through standard numerical methods. A comparison
      with the propagating-beam method shows that the present method has better
      accuracy and is more efficient numerically.

PMID- 19749836
TI  - Lithium niobate guided-wave network for a coherent receiver.
AB  - We report on a packaged LiNbO(3) guided-wave network for a heterodyne receiver
      that combines a tunable 3-dB coupler with temperature- and wavelength-insensitive
      optical compensators for continuous reset-free polarization transformation. A
      fabrication yield of 90% could be achieved by employing indium-tin-oxide-metal
      electrodes. Characteristic data of the device are given.

PMID- 19749837
TI  - Programmable optical interconnections with large fan-out capability using the
      magneto-optic spatial light modulator.
AB  - We report the use of two-dimensional, binary phase-only diffraction gratings
      written on a programmable magnetooptic spatial light modulator to interconnect
      optically an input laser beam to multiple output locations. We show that we can
      achieve programmable weighted interconnects between the source and two output
      locations as well as a fan-out capability to as many as 128 separate output
      locations.

PMID- 19749838
TI  - Pinhole hologram and its applications.
AB  - We propose the use of a pinhole-camera approach to make holograms. On recording
      the object beam passes through a pinhole, forming an image plane hologram, but on
      reconstruction the pinhole can be taken away. The reconstructed image can be
      programmed and processed by using optical information-processing elements placed
      in the position of the reconstructed pinhole or pinholes. Pinhole holography can
      also suppress intermodulation effects. We present brief theoretical
      considerations and experimental results for pinhole holograms produced for
      programmable holographic optical interconnects.

PMID- 19749839
TI  - High-resolution Rayleigh-Brillouin correlation spectroscopy.
AB  - The high spectral resolution inherent in correlation spectroscopy may also be
      used for Brillouin spectroscopy. The heterodyne method described in this Letter
      is based on spontaneous scattering, in contrast to the recently developed high
      resolution gain spectroscopy. A measurement of n-butane vapor is reported as an
      example. A Brillouin linewidth of ~200 kHz was resolved with an accuracy of a few
      percent.

PMID- 19749840
TI  - Time-domain polarization coherent anti-Stokes Raman spectroscopy of Tl atoms:
      dephasing measurements of separate multipole moments.
AB  - Polarization nondegenerate nonstationary coherent anti-Stokes Raman spectroscopy
      was used in measurements of pulse responses for separate electronic multipole
      moments. The 6P(1/2)-6P(3/2) transition of Tl atoms was investigated. Doppler
      dephasing conditions, quantum beats of the hyperfine components of this
      transition are clearly seen when pure anisotropic scattering is registered, but
      they are small in the case of purely antisymmetric scattering. Under collisional
      dephasing conditions the relaxation rates of anisotropic and antisymmetric
      scattering agree with existing theory within +/-5%.

PMID- 19749841
TI  - Efficient diode-array-pumped Nd:YAG and Nd:Lu:YAG lasers.
AB  - Nd:YAG (YAG) and Nd:Lu:YAG (LYAG) are investigated as high-efficiency laser
      materials utilizing a diode-array side-pump geometry. We demonstrate higher laser
      efficiencies than previously reported for transversely pumped YAG. A YAG rod
      yielded an optical slope efficiency of 47.7%, while a LYAG rod yielded an optical
      slope efficiency of 50.3%. Increased performance of these materials is attributed
      to higher pump absorption and lower losses.

PMID- 19749842
TI  - Distortion of femtosecond laser pulses in lenses.
AB  - Large temporal front distortion of femtosecond pulses occurs in lenses having
      chromatic aberration. The effect is due to the difference between the phase and
      group velocities. Equations describing the pulse-front delay in singlet lenses,
      achromats, and compound lenses are presented. The pulse-front delay is several
      orders of magnitude larger than the broadening caused by group-velocity
      dispersion in the lens material. Delays occurring in Fresnel-type zone plates are
      also described.

PMID- 19749843
TI  - Quasi-static electric-field-enhanced degenerate four-wave mixing in a nematic
      liquid-crystal film.
AB  - Degenerate four-wave mixing can be induced or enhanced dramatically when two weak
      overlapping laser beams are incident upon a nematic liquid-crystal film that is
      biased by a quasi-static electric field. This phenomenon is shown to be the
      result of the critical behavior at the Freedericksz transition. The experimental
      results show that the diffracted intensity is proportional to the third power of
      the laser intensity, as expected for a four-wave mixing process, despite the
      strength of the electric-field bias voltage above threshold.

PMID- 19749844
TI  - Raman solitons in media with a Stark shift: soliton regeneration through self
      phase modulation.
AB  - An internal phase-shift mechanism can lead to the amplification of Raman solitons
      even in the presence of coherence decay and detuning. We study here the case of a
      Raman medium with strong ac Stark shift by using both analytical and numerical
      methods. Our results also suggest the possibility of propagating stable transient
      Raman solitons in optical fibers.

PMID- 19749845
TI  - Real-time optical Wiener-Kolmogorov and novelty filtering with phase conjugation.
AB  - Real-time all-optical Wiener-Kolmogorov filtering is demonstrated by using two
      coupled photorefractive phase-conjugate mirrors. A novelty filtering system based
      on the combination of the present operation and the operation of real-time image
      subtraction previously presented [Opt. Lett. 13, 503 (1988)] is outlined. By
      comparing an input signal pattern with a set of known stored patterns, all known
      information in the input would be eliminated from the output, while any novel
      information would appear. This latter scheme could also be used in image
      synthesis applications.

PMID- 19749846
TI  - Dynamics of solitons in coupled optical fibers.
AB  - The dynamics of soliton interaction in two tunnel-coupled optical fibers as a
      function of their phase difference Psi is analytically and numerically
      investigated. It is shown that if Psi = 0 or pi, no energy redistribution occurs
      in the fibers, and the soliton pulses either form a coupled state (Psi = pi) or
      repulse each other and separate during propagation (Psi = 0). Results of computer
      simulations under strong-coupling conditions are presented.

PMID- 19749847
TI  - Raman compensation for a two-channel soliton-based optical fiber communication
      system.
AB  - A technique of Raman compensation for a two-channel soliton-based fiber
      communication system is introduced. By fixing the wavelength spacing between two
      channels, one can calculate the pumping wavelength and intensity in such a way
      that balance between loss and gain is reached for each channel. In this
      computation the Raman conversion between two channels plays an important role in
      simultaneous compensation for both channels.

PMID- 19749848
TI  - Optical wave breaking and pulse compression due to cross-phase modulation in
      optical fibers.
AB  - When a probe pulse copropagates with a pump pulse inside an optical fiber, the
      two can interact through cross-phase modulation. It is shown that an interplay
      between the effects of group-velocity dispersion and cross-phase modulation can
      lead to optical wave breaking that manifests as rapid oscillations near the
      leading or the trailing side of the probe pulse. Qualitative features of this new
      kind of optical wave breaking are discussed, as well as the conditions under
      which it can be observed experimentally. The probe pulse can be compressed
      significantly by optimizing the initial delay between the pump and probe pulses
      even when the two pulses experience normal dispersion in the fiber.

PMID- 19749849
TI  - Linear readout of dynamic phase change in a fiber-optic homodyne interferometer.
AB  - A new technique that provides linear measurement of dynamic phase change in a no
      feedback, no-phase-bias fiber-optic interferometer is described. The phase
      measurement is unaffected by random changes in phase, source intensity, and
      fringe visibility. A minimum detectable phase shift of 0.1 rad has been measured
      for the configuration reported.

PMID- 19749850
TI  - Strong discrimination of transverse modes in high-power laser diodes using Bragg
      channel waveguiding.
AB  - Three-dimensional waveguiding along the channel between two semi-infinite grating
      structures in a dielectric slab waveguide is suggested and analyzed using coupled
      mode theory. In this type of waveguiding, a single transverse mode is possible
      even when the channel width is large, which is important for high-power laser
      diode applications.

PMID- 19749851
TI  - Optics for low-energy communication inside digital processors: quantum detectors,
      sources, and modulators as efficient impedance converters.
AB  - I argue that optics can reduce the energy for irreversible communication of logic
      level signals inside digital switching and processing machines. This is because
      quantum detectors, quantum sources, and modulators can perform an effective
      impedance transformation that matches the high impedances of small devices to the
      low impedances encountered in electromagnetic propagation. Current physics and
      device concepts are sufficient to realize this advantage over electrical
      communications given appropriate integration technology. This energy argument
      suggests that all except the shortest intrachip communications should be optical.

PMID- 19749852
TI  - Backscattering effects in the elastic scattering of p-polarized light from a
      large-amplitude random metallic grating.

PMID- 19749853
TI  - Image synthesis from nonimaged laser-speckle patterns: experimental verification.

PMID- 19749854
TI  - Real-time image processor with stacked liquid-crystal panels based on array
      logic.

PMID- 19749855
TI  - Optical neural-net analog-to-digital converter.

PMID- 19749856
TI  - Continuous-time optical neural network associative memory.
AB  - A continuous-time optical neural network capable of executing a broad class of
      energy-minimizing neural net algorithms has been built. The network is a ring
      resonator comprising a saturable, two-beam amplifier that acts as an optical
      neuron array, two volume holograms that provide global network interconnectivity,
      and a linear, twobeam amplifier that provides sufficient gain to permit network
      oscillation. The network has been used as an associative memory to store and
      recall multiple, nonorthogonal visual images.

PMID- 19749857
TI  - Backscatter-modulation velocimetry with an external-cavity laser diode.
AB  - Feedback phenomena in lasers induce modulation signals that can be used for
      ranging and velocimetry. The modulation depth of a backscatter-modulated
      semiconductor laser diode is considerably enhanced by operating the diode near
      the lasing threshold. In the present work an external cavity is used to maintain
      a spectral linewidth of less than 1 MHz in a diode running at 2.5% of its rated
      power of 30 mW, resulting in a modulation depth enhancement by a factor of 30
      over the high-power limit. Coherent velocimetry has been performed for targets at
      a distance of 50 m, or 20 times farther than the previously published operational
      range for backscatter-modulated laser diodes. Light power of less than 10 pW at
      the collection aperture produces useful modulation signals.

PMID- 19749858
TI  - Extreme-ultraviolet fluorescence from core-excited levels of neutral rubidium.
AB  - Strong extreme-ultraviolet fluorescence originating from core-excited
      autoionizing levels of neutral Rb is observed. Radiative branching ratios
      approaching unity are inferred from the radiative yields. Long autoionizing
      lifetimes and fast radiative rates make these levels promising candidates for
      extreme-ultraviolet laser systems.

PMID- 19749859
TI  - Neutral and ionic excimer molecules produced by reactive kinetics in a laser
      produced plasma.
AB  - The first observation to the authors' knowledge of excimer molecules formed by
      reactive kinetics in a laser-produced plasma is reported. Emission from XeF at
      351 nm and a new ionic excimer (XeRb)(+) at 165 nm have been observed.

PMID- 19749860
TI  - Pseudorandom light from a mode-locked laser.
AB  - We examine the statistical properties of mode-locked laser light in which each
      frequency component is subsequently given a constant, independent, and random
      phase shift. We find that, under certain conditions, this random phase encoding
      produces a pseudorandom light intensity that is statistically equivalent to that
      of a free-running multimode laser, with a negative exponential intensity
      probability distribution.

PMID- 19749861
TI  - Collapse and revival in the micromaser.
AB  - We compare the collapse and revival occurring in the steady-state characteristics
      of the micromaser with the corresponding effects in the Jaynes-Cummings model.

PMID- 19749862
TI  - Optically induced nonresonant changes in the refractive index of Ti:Al(2)O(3).
AB  - Changes in the refractive index of Ti:Al(2)O(3) induced by 10-nsec, 532-nm pump
      pulses from a frequency-doubled Nd:YAG laser have been measured
      interferometrically at 632.8 nm for signal polarizations parallel (pi) and
      perpendicular (sigma) to the c axis. The nonthermal portion of these changes
      decays on a 3-microsec time scale characteristic of the fluorescence lifetime of
      Ti(3+). For the sigma polarization, the nonthermal index change is equal to the
      concentration of excited Ti(3) ions times (4 +/- 2) x 10(-24) cm(3). The change
      for the pi polarization is lower by a factor of 3.7 +/- 0.6. The average change
      is consistent with the value estimated from a harmonic oscillator model that
      considers virtual transitions to a charge-transfer band.

PMID- 19749863
TI  - Measurement of x((3)) and phase shift of nonlinear media by means of a phase
      conjugate interferometer.
AB  - We have constructed a new interferometer that uses two phase-conjugate mirrors.
      This device allows for the measurement of the relative phase shift and the ratio
      of the nonlinear susceptibilities of materials. We have been able to measure weak
      reflectivity signals not detectable by normal degenerate four-wave mixing
      methods. It has been determined that the x((3)) value of colloid semiconductor
      glass OG530 at 532 nm is 7 x 10(-12) esu.

PMID- 19749865
TI  - Dispersion relations and power-flow expressions for nonlinear modes guided by a
      multilayer symmetric dielectric structure: erratum.

PMID- 19749864
TI  - Analysis of coupled photorefractive wave mixing junctions.
AB  - Photorefractive circuits that are based on double phase-conjugate mirror
      junctions are studied theoretically. We analyze in detail the configuration of
      two coupled junctions that is a representative of an experimentally studied class
      and find double-valued solutions for the oscillating beams. A stability analysis
      of the solutions is given.

PMID- 19749866
TI  - Direct determination of strain with diffraction-limit accuracy by moire
      deflectometry.
AB  - In-plane strain is traditionally mapped by fixing a grating onto a test object
      and monitoring its displacements under stress by either a moire method or
      interferometry. The strain (or displacement derivative) is obtained by an
      additional mathematical or moire shearing technique. We suggest an application of
      moire deflectometry that will yield the strain directly. The setup is much
      simpler than existing methods and has the additional advantages of tunable
      sensitivity and immunity to mechanical shock and vibration.

PMID- 19749867
TI  - Design of Dammann gratings for two-dimensional, nonseparable, noncentrosymmetric
      responses.
AB  - Dammann gratings are binary-phase Fourier holograms that are used to generate an
      array of point sources. Using symmetry and separability arguments, we extend
      Dammann's method for generating one-dimensional symmetric arrays to general two
      dimensional responses. Computer-generated holograms are used to verify the
      modified design method.

PMID- 19749868
TI  - Fisher information as the basis for diffraction optics.
AB  - It is shown that the Helmholtz wave equation follows from a new uncertainty
      principle: Given, as data, the position of a photon in an unknown diffraction
      pattern, the estimated position of the centroid of the pattern will suffer
      minimum precision. This implies a maximally spread out diffraction pattern,
      obeying a principle of minimum Fisher information. The minimum is constrained by
      knowledge of the refractive-index function n(x, y, z) of the medium through a
      requirement that the mean-square spatial phase gradient across the medium should
      be generally nonzero. Operationally the principle works directly with intensities
      and not complex amplitudes. As a practical matter the numerical use of the
      intensity-based principle might permit a widening of the known scope of solutions
      to diffraction problems.

PMID- 19749869
TI  - All-optical error-signal generation for backpropagation learning in optical
      multilayer neural networks.
AB  - An all-optical error signal based on the generalized delta rule for
      backpropagation learning in optical multilayer networks is experimentally
      obtained. Optically addressable microchannel spatial light modulators are used to
      perform key functional operations for the error signal such as subtraction, soft
      thresholding, and taking the derivative of the thresholding function. The error
      signals are readily available to adaptive optical multilayer networks in which
      photorefractive crystals are used to determine the connection weights between
      processing units.

PMID- 19749870
TI  - Holographic associative memory for word-break recognition.
AB  - We describe a holographic associative memory that is able to identify individual
      words and insert word breaks in a concatenated word string. The system is shift
      invariant and has error-correction capability. Experimental results obtained from
      the system are presented.

PMID- 19749871
TI  - Optical parallel logic gate using a Pockels readout optical modulator and twisted
      nematic liquid-crystal cells.
AB  - We describe an optical polarization parallel logic gate that is based on the two
      orthogonal polarization states corresponding to the two states of a binary
      system. The logic gate employs a Pockels readout optical modulator (PROM) and 90
      degrees twisted nematic liquid-crystal cells (LCC's). The PROM transforms the
      binary-coded intensities of the input images into two orthogonally polarized
      states of readout light. The LCC is employed as a linear polarization rotator
      that negates the logic state (1 or 0) of the input and output images. Two
      dimensional real-time operation of 14 Boolean logic functions for two input
      images has been demonstrated.

PMID- 19749872
TI  - Solar background rejection by a pressure-broadened atomic resonance filter
      operating at a Fraunhofer wavelength.
AB  - We have calculated the solar background rejection of the Mg atomic resonance
      filter operating at the b(1) Fraunhofer wavelength (518.4 nm) as a function of
      the pressure-broadened filter linewidth. For pressure broadening induced by the
      noble gases the solar background rejection decreases from 93% at a 0.002-nm
      bandwidth to 82-84% at a 0.02-nm bandwidth. Solar background rejection was
      insensitive to buffer gas and was optimum for the noble gas with the smallest
      shift-to-broadening ratio.

PMID- 19749874
TI  - Passively mode-locked cw Coumarin 6 ring dye laser.
AB  - The passive mode locking of a cw Coumarin 6 dye laser in a colliding-pulse ring
      configuration is reported. Pulses of less than 500-fsec duration have been
      obtained from 518 to 554 nm, with the shortest pulses obtained being of 96-fsec
      duration.

PMID- 19749873
TI  - Time-resolved spectroscopy of laser emission from dye-doped droplets.
AB  - Micrometer-sized droplets of Rhodamine 6G solution in water and ethanol are
      irradiated by high-intensity nanosecond pulses from a frequency-doubled Nd:YAG
      laser. Coupling of the spontaneous fluorescence emission with natural resonant
      modes of the spherical droplets results in stimulated emission, with each droplet
      behaving like a laser cavity. Spectral observations suggest that droplet lasing
      emission is supported by resonances of a single mode order. The emission exhibits
      faster rise times and is shorter lived than corresponding bulk-liquid
      fluorescence. Lasing in droplets is generally initiated almost simultaneously
      with elastic scattering, unlike stimulated Raman scattering, which is
      significantly delayed.

PMID- 19749875
TI  - Frequency-modulation mode locking of a Nd(3+)-doped fiber laser.
AB  - Frequency-modulation mode locking of a Nd(3+)-doped fiber laser operating at 1.09
      microm using a bulk phase modulator is reported. The resulting pulses have a 20
      psec duration (FWHM) and a peak power of 1 W. A least-squares fit to the second
      harmonic-intensity autocorrelation trace and the time-bandwidth product of 0.30
      +/- 0.04 suggest that the pulses are bandwidth limited with a sech(2)-type
      profile.

PMID- 19749876
TI  - Continuous-wave synchronously pumped femtosecond dye laser at 1.3 microm.
AB  - We report a synchronously pumped, cw mode-locked, near-IR dye laser based on the
      Kodak Q-switch dye No. 5. Benzyl alcohol is used as the solvent to form a flowing
      dye jet. Synchronously pumped by 2-psec, 950-mW, compressed pulses of a Nd:YAG
      laser, the dye laser can be tuned from 1210 to 1340 nm with a maximum output of 5
      mW and a pulse duration of 600 fsec.

PMID- 19749877
TI  - Opto-optical switching in the infrared using CdTe.
AB  - Opto-optical switching of a 1.06-microm signal beam by another 1.06-microm
      control beam has been observed in CdTe:In. The switching is caused by the
      photocharge created by the control beam and the resultant electric-field
      shielding. This effect can be switched in microseconds and takes advantage of the
      high figure of merit (n(3)r/) of CdTe.

PMID- 19749878
TI  - Asymptotic evolution of transient pulses undergoing stimulated Raman scattering.
AB  - Propagation of short, transient pulses undergoing stimulated Raman scattering
      over long length scales is considered. It is shown that under common experimental
      circumstances the evolution has two different regimes: an I regime, at short
      lengths, where the pump changes little and the Stokes rapidly grows, and a J
      regime, at long lengths, where the Stokes intensity is close to saturation and
      the pump intensity decreases slowly as the square root of distance. The distance
      at which the J regime is reached is determined numerically.

PMID- 19749879
TI  - Optically controlled reflection modulator using GaAs-AlGaAs n-i-p-i/multiple
      quantum-well structures.
AB  - An optically controlled reflection modulator has been demonstrated that consists
      of a combination of a GaAs-AlGaAs n-i-p-i doping structure with a multiple
      quantum-well structure on top of a distributed Bragg reflector, all grown by
      molecular-beam epitaxy. A modulation of approximately 60% is obtained on our test
      structure, corresponding to a differential change of absorption coefficient in
      the quantum wells of approximately 7500/cm. Changes in reflectance can be
      observed with a control beam power as low as 1.5 microW. This device structure
      has the potential of being developed as an optically addressed spatial light
      modulator for optical information processing.

PMID- 19749880
TI  - Second-harmonic radiation from an AlGaAs laser and its application for absorption
      spectroscopy.
AB  - Second-harmonic radiation of several picowatts from various commercial laser
      diodes with several milliwatts of output power has been observed at various
      temperatures from 130 to 310 K. No temperature dependence of the conversion
      efficiency was observed. The spectral width of the second-harmonic radiation was
      limited by that of the fundamental radiation. An application of the internal
      second-harmonic radiation to a spectroscopic light source allowed observation of
      some absorption lines of potassium and aluminum.

PMID- 19749881
TI  - Phase conjugation through Brillouin-enhanced four-wave mixing over an extended
      atmospheric path.
AB  - We report what is to our knowledge the first demonstration of Brillouin-enhanced
      four-wave mixing over a long atmospheric path. Weak laser light reflected from a
      remote retroreflector was input to a high-gain conjugate mirror. The resulting
      amplified output returns to the retroreflector owing to its phase-conjugate
      nature. Despite atmospheric effects the phase-conjugate return energy measured at
      the retroreflector increased by a factor of 10(4) over the initial weak beam.

PMID- 19749882
TI  - Third-order nonlinearity enhancement in an artificial Kerr medium through bulk
      intrinsic birefringence.
AB  - Laser-induced circular birefringence measurements have been performed on a liquid
      suspension of polymer microellipsoids in order to study its optical nonlinearity
      as a function of the host liquid's refractive index n(h). The results show that
      the large values obtained for the chi1221((3)) term (1.6 x 10(-8) esu for n(h) =
      1.330) can be explained with an intrinsic birefringence of the microellipsoids
      relative to their geometrical axes. The obtained values for the refractive
      indices are n || = 1.391 and n perpendicular = 1.368.

PMID- 19749883
TI  - Polarization-rotation switch using picosecond pulses in GaAs.
AB  - Photorefractive and free-carrier nonlinearities in GaAs transfer energy from a
      strong picosecond pump, which is linearly polarized at an arbitrary angle to a
      weak s-polarized probe, into a p-polarized beam propagating in the probe
      direction. By placing the GaAs between a crossed pair of high-quality polarizers
      that are set to extinguish the probe in the absence of the pump, an efficient,
      high-contrast, high-speed optical switch is realized. By varying the pumpprobe
      ratio, delay, fluence, and polarization, we can maximize the intensity of the p
      polarized component. This intensity with the pump present divided by that without
      the pump, the on-off ratio, is approximately 2 at fluences as low as 0.03
      mJ/cm(2) and approaches 10,000 at fluences of 15 mJ/cm(2) and pump polarizations
      of 45 degrees .

PMID- 19749884
TI  - Continuous-wave self-pumped optical phase conjugation in atomic sodium vapor.
AB  - Self-pumped optical phase conjugation has been demonstrated for the first time to
      our knowledge in a resonant atomic system. This process was implemented by using
      a single cw pump beam to excite a sodium-vapor oscillator. The counterpropagating
      optical fields inside this oscillator then combine with the pump beam in an
      internal fourwave-mixing interaction to yield the phase conjugate of the incident
      (pump) beam.

PMID- 19749885
TI  - Detachable 400-MHz acousto-optic phase modulator for a single-mode optical fiber.
AB  - A single-mode-fiber phase modulator was constructed by contacting the fiber with
      a lapped glass capillary tube. The capillary's inner surface provides a long,
      effectively semicircular contact region to the fiber, allowing throughput of
      acoustic waves launched from a thin-film ZnO transducer fabricated directly onto
      the capillary's other lapped face. The device operated at a center frequency of
      416 MHz with a FWHM bandwidth of 14 MHz. The maximum phase shift was 0.033 rad/
      radicalmw, with a largest measured value of 1.2 rad at 1.3-W input electrical
      power.

PMID- 19749886
TI  - High-sensitivity fiber-optic accelerometer.
AB  - We describe a novel accelerometer in which the sensing element is a weighted
      diaphragm. The displacement of the diaphragm produced by acceleration is measured
      using a miniature hemispherical air-spaced Fabry-Perot interferometer, of which
      one mirror is mounted on the diaphragm. The interferometer is illuminated by a
      diode laser and addressed through a monomode optical fiber.

PMID- 19749887
TI  - Inhibited reflection in uniaxial crystals.
AB  - When an ordinary or extraordinary ray that propagates through a birefringent
      crystal is reflected it gives rise to two reflected rays whose directions may be
      calculated with formulas similar to Snell's law for refraction. When the
      reflection angle is greater than the incidence angle there is a critical angle
      for which the reflected ray is grazing, and for values of the incidence angle
      greater than this critical value the reflected ray no longer exists. We call this
      phenomenon inhibited reflection. We show how the critical angles may be
      calculated, and an experiment that visualizes the phenomenon shows good agreement
      with theory.

PMID- 19749888
TI  - Asynchronous optical sampling: a new combustion diagnostic for potential use in
      turbulent, high-pressure flames.
AB  - Asynchronous optical sampling (ASOPS) is a pump-probe method that has strong
      potential for use in turbulent, high-pressure flames. We show that rapid
      measurement of species number density can be achieved by maintaining a constant
      beat frequency between the mode-locking frequencies of the pump and probe lasers.
      We also describe the instrumental timing parameters for ASOPS and consider the
      optimization of these parameters. Measurement of the nanosecond decay for
      electronically excited sodium in an atmospheric flame demonstrates the viability
      of the ASOPS technique in highly quenched flame environments.

PMID- 19749889
TI  - Simultaneous measurement of Raman scattering and laser-induced OH fluorescence in
      nonpremixed turbulent jet flames.
AB  - Spontaneous Raman scattering and laser-induced fluorescence are combined to
      perform simultaneous point measurements of major species concentrations,
      temperature, and hydroxyl radical concentration in turbulent nonpremixed flames.
      The Raman-scattering data for major species concentrations and temperature
      characterize the instantaneous, local, collisional quenching environment of the
      OH molecule. Collisional quenching corrections are applied for each laser shot so
      that absolute hydroxyl concentrations are obtained in turbulent flames using
      linear laser-induced fluorescence.

PMID- 19749890
TI  - Resonant isotopic depletion spectroscopy.
AB  - We have devised a simple new scheme to increase the isotopic selectivity in
      optical rare-isotope detection experiments. We can effectively remove interfering
      isotopes from an atomic beam by optically pumping them into a state that is
      invisible to the optical detection system. The selectivity of this resonant
      depletion scales exponentially with the isotope shift and yields almost unlimited
      selectivity in principle. We have demonstrated a selectivity of 2.3 x 10(5) with
      a single laser excitation in a beam of metastable krypton atoms. With better
      laser stability we may be able to improve the selectivity much further.

PMID- 19749891
TI  - Observation of the cesium clock transition in laser-cooled atoms.
AB  - We have used the light from diode lasers to produce a nearly stationary (upsilon
      ~ 15 cm/sec) sample of atomic cesium in optical molasses that is entirely in the
      F = 3 hyperfine state. In this sample we excite the 9.2-GHz 6SF = 3, m = 0 to F =
      4, m = 0 clock transition. Most of the atoms remain for ~20 msec in the 0.4-cm(3)
      observation region. We observe that transitions take place by monitoring the
      fluorescence when the atoms are illuminated with light tuned to the 6S F = 4 to
      6P(3/2)F = 5 transition. Rabi resonance linewidths of less than 50 Hz are
      obtained.

PMID- 19749892
TI  - Injection-beam parameter optimization of an injection-locked diode-laser array.
AB  - The dependence of the far-field distribution of an externally injection-locked
      array on the width and power of the injected beam was determined by numerical
      simulation. The fraction of total power contained in the diffraction-limited lobe
      portion of the far field was significantly larger for wide-beam injection (95%)
      than for single-point injection (70%). Qualitative agreement with experimental
      results using a 20-element array was observed.

PMID- 19749893
TI  - Measurement of phase shifts introduced by nonlinear optical phenomena on
      subpicosecond pulses.
AB  - A new method for the coherent characterization of subpicosecond optical pulses
      after propagation through a nonlinear medium (i.e., with frequency broadening) is
      described. The phase shift on a single pulse introduced by the nonlinearity can
      be measured with a high dynamic range. We report as one application of this
      technique a measurement of the self-phase modulation incurred by an 800-fsec
      pulse after the pulse propagates along a dispersive single-mode optical fiber.

PMID- 19749894
TI  - Generation of femtosecond pulses by traveling-wave amplified spontaneous
      emission.
AB  - Traveling-wave amplified spontaneous emission (TWASE) on the femtosecond time
      scale is reported. By pumping different dyes with 80-fsec pulses with an energy
      of 4 microJ, we obtain TWASE pulses at several wavelengths between 650 and 800
      nm. After compression by a grating pair the TWASE pulses are almost transform
      limited and shorter than the pump pulses. The temporal jitter between the pump
      and TWASE pulses is smaller than the pump-pulse duration.

PMID- 19749895
TI  - Enhanced Raman scattering in a flowing plasma.
AB  - The growth rate for the Raman scattering instability has been found for the case
      when the plasma flow has a component perpendicular to the wave vector of the
      pump. Such a configuration allows the pump and the scattered waves to be linearly
      converted into corresponding longitudinal waves. The linear conversion has a
      resonant character that results in an enhancement of the growth rate of the
      parametric process.

PMID- 19749896
TI  - Double phase-conjugate mirror using a photorefractive Bi(12)TiO(20) crystal.
AB  - Experimental results are reported for four-wave mixing at 633 nm with a
      photorefractive Bi(12)TiO(20) crystal in a double phase-conjugate mirror
      geometry. Recording in the presence of an alternating electric field with optimum
      focusing of interacting Gaussian beams yields up to 40% diffraction efficiency
      for the hologram.

PMID- 19749897
TI  - Impulse-response function of photorefractive phase conjugation.
AB  - Explicit expressions for the impulse-response function of a photorefractive phase
      conjugator are derived. The expressions are in the form of an infinite series of
      Bessel functions. The results are derived by using the undepleted pump
      approximation and are therefore valid at least for small time intervals, even
      when the conjugator is unstable.

PMID- 19749898
TI  - Fiber-optic sensing of voltages by line integration of the electric field.
AB  - A fiber-optic sensor that is sensitive to the line integral of the electric field
      is presented. The sensor detects electric-potential differences by adding the
      scalar products of the local electric fields along the integration path times the
      path-segment vectors. This is achieved by exploiting symmetry properties of the
      converse piezoelectric effect. The sensor principle is experimentally
      demonstrated. Important performance parameters including integration accuracy,
      dynamic range, linearity, and bandwidth are examined.

PMID- 19749899
TI  - Very low-loss Y-junction power divider.
AB  - The design of an efficient wide-angle dielectric optical waveguide Y-junction
      power divider is outlined. The method has several degrees of freedom that can be
      used to optimize the device's performance to achieve minimization of the
      radiation loss for a specified mode at the input and equalization of the modal
      losses in a dual-mode device.

PMID- 19749900
TI  - Interferometric tomography of continuous fields with incomplete projections.
AB  - Interferometric tomography in the presence of an opaque object has been
      investigated. In principle the developed iterative algorithm does not need to
      augment the missing information. It is based on the successive reconstruction of
      the difference field, the difference between the object field to be reconstructed
      and its estimate, in the defined region only. The application of the algorithm
      results in stable convergence.

PMID- 19749901
TI  - Variable-finesse wideband Fabry-Perot wavemeter for far-infrared and millimeter
      waves.
AB  - A high-bandwidth scanning Fabry-Perot wavemeter using polarizing reflectors is
      developed for far-infrared and millimeter waves. The strip directions of the two
      striped polarizing reflectors are made slightly different, and the reflectivity
      finesse is varied according to the relative angle of the two strip directions. By
      adjusting this angle one obtains the fringes of Fabry-Perot interference for a
      wide range of far-infrared and millimeter wavelengths. Experimental results show
      that the wavelength measurement range is approximately 100 to 3000 microm.

PMID- 19749902
TI  - Two-photon-excited stimulated emission from atomic oxygen in flames and cold
      gases.
AB  - We report detection of stimulated emission from the atomic-oxygen 3 (3)P-3 (3)S
      transition at 845 nm after two-photon excitation of the 2 (3)P-3 (3)P transition
      using 226-nm laser radiation. We study this stimulated emission process in flames
      and in room-temperature flows of O(2) and N(2)O and compare its behavior with
      that of fluorescence signals acquired simultaneously. Rapid depletion of the
      laser-excited state by the stimulated emission process may have an impact on the
      use of diagnostic techniques based on multiphoton excitation in oxygen and in
      other species. The strength of the stimulated emission signal suggests that it
      may have applications as a diagnostic technique.

PMID- 19749903
TI  - Index-guided arrays with a large index step.
AB  - The mode-selection mechanism operative in a new class of large-index-step index
      guided arrays is elucidated, and it is shown that such arrays may be designed to
      operate stably in the fundamental mode at high power levels. In contrast to
      evanescently coupled arrays, these devices operate in a new set of so-called
      leaky modes. The calculations demonstrate a significant discrimination between
      the fundamental and high-order leaky modes that is sensitive to the widths of the
      high-index coupling regions but insensitive to the drive current. This resulting
      mode discrimination combined with the inherently large index step present in
      these devices should allow them to operate stably under cw conditions and/or at
      high drive currents.

PMID- 19749904
TI  - Ultrafast switching with a single-fiber interferometer.
AB  - All-optical switching with femtosecond and picosecond pulses is demonstrated in a
      single-fiber interferometer in which the role of the two arms is played by two
      mutually delayed versions of the same pulse. This technique eliminates thermal
      and acoustic imbalances of the interferometer.

PMID- 19749905
TI  - Pump-pulse effects in hybridly mode-locked dye lasers.
AB  - The pump pulse of a hybridly mode-locked laser provides additional parameters for
      system optimization. We use a semiclassical model to explore numerically the role
      of the pump pulse in the ultrashort pulse production of a hybridly mode-locked
      dye laser. Pump pulses of lengths less than ~1 psec are found to correspond to
      Dirac delta functions and deliver the shortest output pulses. We conclude that
      existing dye-laser systems would yield a twofold to threefold shortening in
      output pulse widths and a threefold to fivefold increase in peak power if pump
      pulses of 1 psec were used. We note that a 1-psec pump pulse is attainable using
      fiber-compression techniques.

PMID- 19749906
TI  - Picosecond pump-probe interferometric measurement of optical nonlinearity in
      semiconductor-doped fibers.
AB  - Refractive and absorptive optical nonlinearity can be distinguished using a pump
      probe interferometric technique with picosecond time resolution. The method is
      applied to both resonant and nonresonant nonlinearities in optical fibers and
      reveals marked differences between the relaxation behavior of the refractive and
      absorptive nonlinearity in certain cases. A monomode fiber doped with CdS(x)Se(1
      x) semiconductor nanocrystals exhibits a large optically induced phase shift with
      ~10-psec relaxation time, which is many orders faster than the relaxation of the
      absorptive nonlinearity under identical conditions.

PMID- 19749907
TI  - Parametric soliton laser.
AB  - The parametric soliton laser is described. It operates through parametric four
      photon mixing in a synchronously pumped ring cavity. A dispersion-shifted single
      mode fiber at 1.525 microm is used, and the pump wavelength is set at the
      wavelength of zero chromatic dispersion. Clear evidence of a threshold was found,
      and a pulse width of 210 fsec was obtained. An intensity-dependent carrier
      frequency was observed and is explained by phase matching through the nonlinear
      index.

PMID- 19749908
TI  - Phase-conjugate Fizeau interferometer.
AB  - We describe a phase-conjugate interferometer that consists of a partially
      transmitting conventional mirror placed in front of and in close proximity to a
      phase-conjugate mirror. The interferometer is self-referencing, compact, and
      insensitive to environmental disturbances, provides twice the sensitivity of
      conventional (nonphase-conjugate) interferometers, and produces a direct
      representation of an incident wave front. We have constructed such a device using
      internally self-pumped phase conjugation in barium titanate and have used the
      device to characterize the wave front produced by an aberrated optical system.

PMID- 19749909
TI  - Continuous coherent erasure of dynamic holographic interconnects in
      photorefractive crystals.
AB  - The holographic double-exposure technique is applied to elementary gratings in
      photorefractive crystals. The result is an interconnection strength that is a
      continuous function of the phase shift between the two gratings. In fan-in and
      fan-out situations, where multiple phase gratings are required, it is possible to
      alter each interconnection separately without affecting the others.

PMID- 19749910
TI  - Brillouin gain variation due to a polarization-state change of the pump or Stokes
      fields in standard single-mode fibers.
AB  - The effect of pump or Stokes field polarization-state changes on Brillouin gain
      is investigated in standard (non-polarization- maintaining) single-mode fibers
      with a modal birefringence of ~10(-7). The Brillouin gain change due to
      polarization azimuth variation of the input pump or Stokes field reaches +/-31%
      of the average gain expected for a completely scrambled polarization state. This
      polarization effect on the Brillouin gain may lead to cross-talk fluctuation in
      bidirectional coherent transmission systems and to degradation of Brillouin
      amplifier performance.

PMID- 19749911
TI  - Effects of stimulated Brillouin scattering on the performance of polarization
      maintaining all-fiber ring resonators.
AB  - Low-loss, polarization-maintaining, all-fiber ring resonators can exhibit
      nonlinear propagation effects occurring at relatively low input powers.
      Observations have been made of stimulated Brillouin scattering with input powers
      of 65 microW that lead to significant nonlinear variations in the measured value
      of finesse owing to depletion of the power through the stimulated-Brillouin
      scattering process. Variations of measured finesse from 320 to 210 have been
      observed for a variation in input power of 155 microW. The nature of this
      variation in resonator finesse with input power has been studied and is shown to
      depend on the level of the input power when the resonator response is optimized.

PMID- 19749912
TI  - Surface-coupled LiNbO(3) guided-wave structure.
AB  - LiNbO(3) waveguide substrates are terminated in out-of-plane 45 degrees -angled
      knife edges for the first time to our knowledge. This termination causes the
      guided wave to be totally internally reflected with excellent efficiency into or
      out of the waveguide surface, which allows new approaches for hybrid integration.

PMID- 19749913
TI  - Accurate numerical method for the calculation of bending loss in optical
      waveguides using a matrix approach: erratum.

PMID- 19749914
TI  - Joint-transform correlator systems using deformable-mirror spatial light
      modulators.
AB  - Two joint-transform correlator systems based on deformable-mirror-device (DMD)
      spatial light modulators and charge-coupled-device (CCD) video cameras are
      described. The system designs provide for real-time correlation between video
      formatted input scenes and stored reference images. The DMD light modulators are
      used exclusively for inputting data in the optical stages of these systems, and
      the CCD cameras are used to provide the critical square-law detection required in
      joint-transform architectures. Experimental verification of the functionality of
      these DMD/CCD joint-transform systems is also presented.

PMID- 19749915
TI  - Bragg holographic structures for XUV applications: a new approach.
AB  - We report a new technique for producing high-efficiency XUV Bragg (volume)
      holographic optical elements by recording interference patterns in a
      photosensitive coating in either the visible or XUV region. Theoretical
      calculations and analysis of experimental results have successfully demonstrated
      the significance of this new fabrication methodology for XUV holographic optical
      elements, with over 25% diffraction efficiency achieved. In addition, volume
      holographic optics offer high flexibility in conventional and nonconventional
      operations, high laser-damage threshold and temperature stability, low surface
      roughness, and cost effectiveness in mass production.

PMID- 19749916
TI  - Ultrafast noncollinear second-harmonic-generation-based 4 x 4 optical switching
      array.
AB  - A noncollinear second-harmonic-generation-based 4 x 4 switchable computational
      array is experimentally demonstrated. Picosecond binary scalar and vector-matrix
      multiplication results are presented.

PMID- 19749917
TI  - Evidence for laser cooling in a magnesium atomic beam.
AB  - Laser cooling in a Mg atomic beam is reported for the first time to our
      knowledge. Previous cooling experiments were performed by using visible or
      infrared lasers. The Mg atoms were cooled by using an intracavity frequency
      doubled dye laser at 285 nm to reach the resonant (1)S(0)-(1)P(1) transition.
      Evidence of laser cooling was obtained even with the limited available laser
      power ( approximately 1-2 mW).

PMID- 19749918
TI  - Multiterawatt subpicosecond KrF laser.
AB  - A 390-fsec pulse with a peak power of 4 TW has been obtained in KrF, yielding an
      output energy of 1.5 J from an electron-beam-pumped amplifier with an active
      cross section of 320 cm(2). The amplified spontaneous emission is as low as 1.8%
      in energy. An initial pulse width of 210 fsec is increased to 390 fsec in the
      amplifier, mainly as a result of linear dispersion in the thick windows and
      lenses used throughout the system. Nonlinear absorption and self-phase modulation
      are not significant in the 2.5-cm-thick CaF(2) output window at an intensity of
      13 GW/cm(2).

PMID- 19749919
TI  - Many-body effects in gain and refractive-index spectra of bulk and quantum-well
      semiconductor lasers.
AB  - Gain and refractive-index spectra for bulk and quantum-well semiconductor lasers
      are computed using quantum-mechanical many-body theory. The results clearly show
      the influence of band-gap renormalization, broadening, and Coulomb enhancement on
      the gain, the absorption, and the refractive-index spectra.

PMID- 19749920
TI  - Mode locking by a frequency-doubling crystal: generation of transform-limited
      ultrashort light pulses.
AB  - Transform-limited ultrashort green and infrared light pulses have been generated
      from a Nd:YAG laser mode locked by an intracavity second-harmonic crystal in
      combination with a dichroic output coupler. The mode-locking process is based on
      substantial reconversion of the second-harmonic radiation back into fundamental
      radiation after reflection by the dichroic mirror. With this technique light
      pulses as short as 45 psec have been generated.

PMID- 19749921
TI  - Evolution of gain and absorption in a cw mode-locked dye laser.
AB  - We have measured the evolution of the gain (Rhodamine) and absorber (DODCI) dyes
      inside a cw mode-locked dye laser. The recovery time of each dye after the
      passage of the intracavity pulse was much longer than 1 psec. However, a probe
      pulse passing through one dye and then through the other dye experienced a net
      gain that lasted only ~1 psec, the duration of the pulse. The results are
      consistent with the mechanism of pulse formation in a dye laser mode locked by a
      slow saturable absorber proposed by New and Haus [IEEE J. Quantum Electron. QE
      10, 115 (1974); QE-11, 736 (1975)].

PMID- 19749922
TI  - Wavelength-tunable synchronous amplification of picosecond dye-laser pulses near
      1 microm.
AB  - We report use of the dye Styryl 13 for picosecond synchronous amplification in a
      noncollinear longitudinally pumped dye-amplifier arrangement. In this manner we
      obtained pulses ~5 psec in duration, tunable from 900 to 990 nm, with energy up
      to 300 microJ, and focusable to near the diffraction limit.

PMID- 19749923
TI  - Nonlinear Gaussian expansions of stochastic processes: super-Gaussian effects in
      coherent anti-Stokes Raman spectroscopy.
AB  - We propose a new approach to the analysis of stochastic processes (such as
      fluctuating laser fields) with super-Gaussian statistics: the expansion of
      stochastic processes in terms of first and higher powers of Gaussian components,
      which are used like a basis set. This approach is applied to treat the super
      Gaussian correlation effects observed in coherent anti-Stokes Raman scattering
      experiments using frequency-doubled pump laser fields. Our results give much
      better agreement with experimental data than previous theories do.

PMID- 19749924
TI  - Broad bandwidths from frequency-shifting solitons in fibers.
AB  - By pumping a fiber in the anomalous group-velocity-dispersion regime with a color
      center laser we generate pulses with tau greater, similar 100 fsec covering a
      wide spectral range of 1.55 microm < lambda < 1.85 microm. Cross-correlation
      measurements show the lack of correlation between different parts of the
      spectrum. Computer simulations show that modulation instability and the soliton
      self-frequency-shift effect initiate a multisoliton collision process that
      results in narrow, high-intensity, fundamental solitons. The observed broad
      spectra correspond to an ensemble average over these solitons, which start from
      noise and frequency shift by different amounts.

PMID- 19749925
TI  - Time dependence of quantum fluctuations in solitons.
AB  - We investigate quantum fluctuations in coherent solitons propagating in a
      dispersive nonlinear waveguide. Optimal squeezing or noise reduction occurs for a
      local oscillator width near the soliton width in time, i.e., the quantum
      fluctuations are localized.

PMID- 19749926
TI  - Analysis of absorbing and leaky planar waveguides: a novel method.
AB  - We present a simple and general approach for analysis of absorbing and leaky
      waveguides. The real and imaginary parts of the propagation constant beta of a
      planar optical waveguide are obtained by evaluating a function, defined through
      the eigenvalue equation, in real beta. The applicability of the method is
      demonstrated for simple structures. To apply the method for arbitrarily graded
      inhomogeneous or multilayered structures we use a simple matrix approach to
      obtain the eigenvalue equation. The method is straightforward, accurate, and
      requires no iteration in the complex beta plane.

PMID- 19749927
TI  - Measurement of the wave front of a pulsed dye laser using an integrated-optics
      sensor with 200-nsec temporal resolution.
AB  - We report the use of an integrated-optics wave-front measurement sensor to
      measure with 200-nsec temporal resolution the phase and intensity at the aperture
      of a high-power (3.5-MW peak power) flash-lamp-pumped pulsed dye laser. The
      measurements reveal large fluctuations of the dye-laser wave front during the 2
      microsec duration of the laser pulse. The fluctuations and the resulting poor
      beam quality are attributed to inhomogeneous heating of the dye during the pulse.
      These high-temporal-resolution measurements, which are not possible with other
      state-of-the-art wave-front analyzers, explain the previously measured poor beam
      quality of the laser.

PMID- 19749928
TI  - Space-variant operations using an optical parallel processor based on
      polarization encoding.
AB  - Space-variant logic operations are carried out using an optical parallel
      processor that is based on polarization encoding and subsequent spatial
      separation of the encoded light. In this processor a liquid-crystal spatial light
      modulator is used as an operational kernel that allows a programmable space
      variant operation to be performed on a real-time basis by spatially filtering the
      encodedlight pixel by pixel.

PMID- 19749929
TI  - Energy transfer and the photon lifetime within an aerosol particle.
AB  - The theory of enhanced energy transfer within an aerosol particle based on donor
      coupling to morphological dependent resonances is tested for the first time to
      our knowledge. The correspondence between theory and experiment is good and
      allows one to obtain the photon lifetime within the longest-lived resonances. A
      comparison between this lifetime and the lifetime as obtained by Mie theory is
      discussed.

PMID- 19749930
TI  - Ultranarrow extraresonant antiholes in pump-probe spectroscopy induced by
      inelastic collisions.
AB  - Pump-probe spectroscopy with copropagating pump and probe beams of an open two
      level system where, as a result of inelastic collisions, the lower state of an
      optical transition relaxes faster to reservoir states than the upper state does,
      may yield an antihole in the probe spectral profile whose linewidth is subnatural
      and unaffected by Doppler broadening.

PMID- 19749931
TI  - Birefringence of solid-state laser media: broadband tuning discontinuities and
      application to laser line narrowing.
AB  - Spectral consequences that result from using birefringent media with broadband
      gain inside of laser cavities containing polarizing elements are described. We
      show that the laser intensity is modulated as a function of the output frequency
      unless the cavity elements are carefully aligned so that their polarization axis
      coincides with a principal optical axis of the gain medium. Analysis of the
      tuning characteristics of a birefringent polarizationdependent gain medium is
      exploited to provide a simple method for line narrowing the laser output. By
      introduction of an intracavity birefringent compensator the narrow-band output
      can be continuously tuned. Experimental results for alexandrite lasers are
      presented.

PMID- 19749932
TI  - Focusing effects of induced phase modulation on a probe pulse propagating in a
      chi((3)) medium.
AB  - The focusing effects of induced phase modulation generated by a strong pump on
      the propagation of a probe Gaussian pulse in a chi((3)) medium are computed. The
      probe diameter, the radius of curvature, and the phase are expressed as function
      of the primary pulse (pump) characteristics. It is proved that waveguiding of the
      probe by the pump is possible.

PMID- 19749933
TI  - Increased frequency conversion of Nd:YAG laser radiation with a variable
      reflectivity mirror.
AB  - The frequency-doubling efficiency of a Nd:YAG laser was increased by using a
      variable-reflectivity-mirror unstable resonator. At 5 Hz as much as 385 mJ of
      green light was obtained with an efficiency of 61%. The divergence of the
      converted light, which was 0.26 mrad at 0.5 Hz, close to the diffraction limit,
      increased to 0.69 mrad at 5 Hz.

PMID- 19749935
TI  - Four-wave mixing in photorefractive crystals with depleted pumps: an analytical
      treatment.
AB  - We present an analytical approximative solution of four-wave mixing in
      photorefractive crystals with depleted pumps for the case of a negative coupling
      coefficient and then discuss the solution.

PMID- 19749934
TI  - Third-order optical sum-frequency generation in micrometer-sized liquid droplets.
AB  - A series of discrete emission peaks is detected from single micrometer-sized
      droplets. The series starts at the blue third harmonic of the input IR radiation
      and extends to the red as a result of four-wave mixing of the input radiation and
      the multiorder stimulated-Raman-scattering radiation. The detected third-harmonic
      intensity from a single liquid droplet is several orders of magnitude larger than
      that from an optical cell containing the same liquid.

PMID- 19749936
TI  - Optical-fiber-attenuation investigation using stimulated Brillouin scattering
      between a pulse and a continuous wave.
AB  - A new technique for measuring optical-fiber-attenuation characteristics is
      described. The technique uses stimulated Brillouin scattering in the fiber
      between a counterpropagating pulsed pump wave and a cw Stokes probe wave. Fiber
      attenuation is estimated nondestructively from amplification of the probe wave
      through stimulated Brillouin scattering. Experiments with a 5.2-km-long single
      mode fiber reveal that the output signal is approximately 100 times that of the
      Rayleigh backscattered signal observed in conventional optical time-domain
      reflectometry. The signal fluctuation due to polarization-dependent Brillouin
      gain is successfully removed by polarization averaging.

PMID- 19749937
TI  - Design of wide-core planar waveguides by an inverse scattering method.
AB  - An inverse scattering method is used to design single-mode planar optical
      waveguides. Waveguides with wider cores compared with those designed by direct
      scattering methods are obtained, and a numerical example is given.

PMID- 19749938
TI  - Molecular velocity imaging of supersonic flows using pulsed planar laser-induced
      fluorescence of NO.
AB  - A technique is described for imaging components of velocity in a gaseous flow
      field by using pulsed planar laser-induced fluorescence. The technique is based
      on the fluorescence detection of Doppler-shifted absorption that results when a
      spectrally narrow absorption line is excited with a broadband laser. Results
      obtained in a Mach 7 underexpanded supersonic jet, seeded with NO, are presented.
      The practical extension of this technique to single-shot measurements of two
      velocity components is discussed.

PMID- 19749939
TI  - Multiplexed phase-encoded lenses written on spatial light modulators.
AB  - We report the writing of Fresnel phase-encoded lenses onto programmable spatial
      light modulators (SLM's). When the product of the phase-encoded lens and the two
      dimensional Fourier transform of a desired output spatial pattern is written onto
      the SLM, the desired spatial pattern is focused at programmable distances from
      the SLM. More importantly the inverted version of the desired pattern normally
      produced is encoded onto a diverging beam and is not imaged. Theoretical analysis
      and experimental results using the magneto-optic SLM are presented.

PMID- 19749940
TI  - Multiple-bit long-term data storage by backward-stimulated echo in
      Eu(3+):YAlO(3).
AB  - We have observed faithful storage and retrieval of multiple data pulses for up to
      5 h in Eu(3+):YAlO(3) crystal by using the backward-stimulated echo. We find no
      loss of echo fidelity as the storage time is increased. Furthermore the lack of
      cross talk between the input data pulses suggests that faithful long-term storage
      and retrieval of a large number of data pulses are possible. Our measured echo
      storage lifetime of 3.8 h is to our knowledge the longest reported thus far.

PMID- 19749941
TI  - Arithmetic operations in optical computations using a modified trinary number
      system.
AB  - A modified trinary number (MTN) system is proposed in which any binary number can
      be expressed with the help of trinary digits (1, 0, 1 ). Arithmetic operations
      can be performed in parallel without the need for carry and borrow steps when
      binary digits are converted to the MTN system. An optical implementation of the
      proposed scheme that uses spatial light modulators and color-coded light signals
      is described.

PMID- 19749942
TI  - Image correlators using optical memory disks.
AB  - Image correlators are described and experimentally demonstrated that are
      implemented using optical memory disks to store a large library of reference
      images.

PMID- 19749943
TI  - Concentration-dependent energy-transfer processes in Er(3+)-and Tm(3+)-doped
      heavy-metal fluoride glass.
AB  - The energy-transfer rate from the Er(3+)(4)I(13/2) level to the Tm(3+)(3)H(4)
      level (C(11')N(T)) in BaF(2)/ThF(4) fluoride glass is measured and calculated.
      The results can be used to determine whether rate equations can be used to
      predict energy-transfer rates.

PMID- 19749944
TI  - 2.07-microm cw diode-laser-pumped Tm, Ho:YLiF(4) room-temperature laser.
AB  - Continuous-wave action is obtained at 2.07 microm from a 2-mm-long Tm-sensitized
      Ho:YLiF(4) crystal at room temperature when longitudinally pumped by a pair of
      diode-laser arrays. Laser output power at 300 K is 26 mW, with a 30% slope
      efficiency and a lasing threshold of 108 mW. A maximum output power of 187 mW is
      obtained from a 4-mm-long crystal at 77 K, with a 67% slope efficiency. A
      preliminary demonstration of cavity Q switching produced 165 microJ of pulse
      energy at a repetition rate of 100 Hz.

PMID- 19749945
TI  - High-power narrow-linewidth Er(3+)-doped fiber laser.
AB  - We describe a high-power Er(3+) laser that produces 56 +/- 2 and 96 +/- 5 mW of
      power at room and liquid-nitrogen temperatures, respectively. Slope efficiencies
      of 10 +/- 1% and 14 +/- 1% with corresponding thresholds of 44 +/- 4 and 6.8 +/-
      0.6 mW are obtained at high and low temperatures. An intracavity etalon composed
      of the output mirror and the fiber end face restricted the output linewidth to
      620 +/- 60 MHz.

PMID- 19749946
TI  - Solid-state XeF(D ? X) laser at 286 nm.
AB  - XeF-doped Ar crystals pumped at 248 nm undergo stimulated emission over the D-X
      band at 286 nm. Spectral narrowing measurements indicate a net gain in excess of
      6 cm(-1).

PMID- 19749947
TI  - Synchronously pumped subpicosecond dye oscillator-amplifier system.
AB  - A tunable subpicosecond dye oscillator-amplifier system that produces 0.20-mJ,
      190-fsec pulses at 620 nm in a nearly diffraction-limited beam is demonstrated.
      The output pulse is temporally broadened by 10% relative to the input pulse. The
      system consists of a synchronously pumped subpicosecond dye laser followed by a
      dye amplifier that is quasi-longitudinally pumped using the frequency-doubled
      output from a Nd:YAG regenerative amplifier.

PMID- 19749948
TI  - Generation and control of solitons and solitonlike pulses in a femtosecond ring
      dye laser.
AB  - We control the generation of solitons and solitonlike pulses in a passively mode
      locked dye laser by adjustment of group-velocity dispersion, self-phase
      modulation, and spectral filtering. Without spectral filtering, periodic pulse
      shaping reminiscent of higher-order solitons is observed. The pulses differ from
      the classic solitons because of additional shaping mechanisms. With spectral
      filtering, pulses are generated that can be described analytically as asymmetric
      N = 2 solitons. The results indicate an effect analogous to the soliton self
      frequency shift observed in optical fibers. The remarkable stability achieved
      allows for accurate characterization and control.

PMID- 19749949
TI  - Broadband cubic-phase compensation with resonant Gires-Tournois interferometers.
AB  - We discuss our design, construction, and characterization of thin-film Gires
      Tournois interferometers for cubic-phase correction of ultrashort (<10-fsec)
      laser pulses. We include in the theory of the group delay of Gires-Tournois
      interferometers the dispersion of the thin-film layer, an important effect in the
      broadband limit. We characterize and use specific broadband, high-efficiency, low
      dispersion substrates for this application.

PMID- 19749950
TI  - Measurement of dephasing time using incoherent light in the Kerr shutter
      configuration.
AB  - We propose a convenient signal-selective method to measure the dephasing time
      using incoherent light performed in the Kerr shutter configuration. The advantage
      of this method is easy alignment, which allows one to obtain a better signal-to
      noise ratio than with ordinary forward two-beam degenerate four-wave mixing. The
      dephasing time of Cresyl Violet doped in a polymethyl methacrylate film obtained
      by this method is compared with the result from ordinary two-beam degenerate four
      wave mixing.

PMID- 19749951
TI  - Evidence for multistability of light solitons in SF(6) absorption measurements.
AB  - We report experimental evidence of the multistability of reshaped pulses that are
      observed when a 1.5-nsec CO(2)-laser pulse interacts with a pure SF(6) absorber.
      The data demonstrate that the dependence of the reshaped pulse delay on peak
      power is not a single-valued function under various experimental conditions.

PMID- 19749952
TI  - Photorefractive dark conductivity in Cr-doped strontium barium niobate.
AB  - We present the theoretical and experimental results of photorefractive two-beam
      coupling in Cr-doped strontium barium niobate:60, using thermal excitation (i.e.,
      dark conductivity) to model the experimentally observed temperature-dependent
      behavior of the two-beam coupling constant and response time.

PMID- 19749953
TI  - Ring self-pumped phase conjugator using total internal reflection in
      photorefractive strontium barium niobate.
AB  - We report the design and operation of a photorefractive ring self-pumped phase
      conjugator using total internal reflection in strontium barium niobate. Phase
      conjugate reflectivity and fidelity are measured and compared with those of the
      conventional total-internal-reflection phase conjugator.

PMID- 19749954
TI  - Numerical and experimental comparison of spectral broadening of femtosecond
      optical asymmetric pulses in a monomode fiber.
AB  - The experimental self-phase-modulation spectra of 55-fsec optical pulses after
      propagation along 11 mm of monomode fiber are compared with the computed spectra
      obtained by a numerical solution of the nonlinear wave-propagation equation. We
      discuss the relative importance of the pertinent additional terms (third-order
      disperson, shock, and reflection terms) and the importance of an asymmetric
      profile of the input pulses. This asymmetry is found to be a dominant parameter
      in the self-phase-modulation process. No other physical effect must be used in
      order to explain the observed spectra, which agree well with the numerical data.

PMID- 19749955
TI  - Holographic detection of optical squeezed states.
AB  - A holographic technique is described that permanently records and detects the
      quadrature components of optical squeezed states.

PMID- 19749956
TI  - Velocity measurement by H2O photolysis and laser-induced fluorescence of OH.
AB  - Experimental results in a uniform, supersonic, free-jet flow containing water
      vapor show that enhancement of OH concentration by focused UV photodissociation
      of H(2)O at 248 nm is an excellent tagging mechanism for velocity measurements.
      Two-dimensional images of OH fluorescence with a vidicon show a narrow initial
      enhanced OH zone along a straight line limited by the jet diameter. Fluorescence
      induced by a time-delayed pulsed dye laser documents the convection of this
      enhanced OH by the uniform core flow and reveals sharply stretched edge regions
      due to the shear layer with ambient air. The core flow velocity measurements are
      in agreement with predicted values.

PMID- 19749957
TI  - Influence of the input state of polarization on interferometric and polarimetric
      measurements of birefringence.
AB  - Using a general model to schematize polarimetric and interferometric
      measurements, we derive the dependence of the output signal on the input state of
      polarization. We show that in any birefringent medium, in addition to the
      eigenvectors that maximize the interferometric phase signal, there exist dual
      vectors that maximize the amplitude of the polarimetric signal. The dual vectors
      lie on the maximum circle normal to the eigenvector axis.

PMID- 19749958
TI  - Iterative encoding of high-efficiency holograms for generation of spot arrays.
AB  - An iterative discrete on-axis encoding method for computer-generated holograms
      (termed IDO encoding) has been developed. The binary IDO method employs simulated
      annealing to optimize the hologram phase delay and reduce sensitivity to
      fabrication tolerances. Computer-simulation results indicate that binary phase
      IDO encoding is capable of generating two-dimensional spot arrays with
      diffraction efficiencies larger than 70%. An experimentally fabricated hologram,
      designed to account for a 6% manufacturing hologram thickness tolerance, produced
      a 3 x 3 array of spots with 59% diffraction efficiency. The binary IDO algorithm
      can be employed to encode arbitrary images with twofold rotation symmetry.

PMID- 19749959
TI  - Optoelectronic implementation of mathematical morphology.
AB  - An optoelectronic implementation based on optical neighborhood operations and
      electronic nonlinear feedback is proposed to perform morphological image
      processing such as erosion, dilation, opening, closing, and edge detection.
      Results of a numerical simulation are given and experimentally verified.

PMID- 19749960
TI  - All-optical neural network with inhibitory neurons.
AB  - A Hopfield-type neural network with only inhibitory interconnections is shown to
      perform similarly to networks with both inhibitory and excitatory interconnects.
      With the use of only inhibitory neurons the need to subtract light intensities is
      eliminated, so an all-optical neural network can be realized. This realization is
      achieved with a liquid-crystal light valve for implementing a two-dimensional
      array of 16 inhibitory neurons and an array of subholograms for the
      interconnections. Two stable states that can be retrieved from noisy optical
      inputs are demonstrated.

PMID- 19749961
TI  - Observation of the Stark effect in high-overtone band transitions of NH(3).
AB  - A sensitive dye-laser spectrometer is constructed to observe the Stark effect of
      weak-overtone transitions in NH(3). A DeltaP/P sensitivity of 10(-6) is achieved
      with the help of a laser-noise-reduction system. A relatively short (30-cm) and
      narrow-gap (0.25-mm) Stark electrode makes it possible to apply a high electric
      field on molecular gas at low pressure (~1 Torr). The Stark components of the
      upsilon = 5 overtone band transitions of NH(3) are well resolved. The rotational
      assignments are confirmed, and the dipole moment in the upsilon = 5 excited
      vibrational state is determined to be 1.40 +/- 0.02 D.

PMID- 19749962
TI  - Emission properties of surface-emitting distributed-feedback and distributed
      Bragg-reflector semiconductor lasers.
AB  - We use a single-mode transfer equation model to study the performance of vertical
      cavity surface-emitting distributed- feedback (DFB) and distributed-Bragg
      reflector (DBR) semiconductor lasers above threshold. We find that DBR lasers
      exhibit less envelope spatial hole burning than both single and double phase
      shifted DFB lasers and therefore may achieve more stable single-longitudinal-mode
      operation.

PMID- 19749963
TI  - Mode size and time duration fluctuations in a picosecond Nd:YAG laser.
AB  - A new technique is successfully used to analyze in real time the pulse-to-pulse
      fluctuations of mode size and time duration in a picosecond Nd:YAG laser. In
      particular we show that the pulse length (30 psec) of our active-passive mode
      locked Nd:YAG laser is stable to within 10% when the cavityis perfectly tuned and
      the saturable absorber is fresh. This technique is experimentally shown to be
      effective and reliable for real-time analysis of the stability of ultrashort
      laser pulses undera broad range of experimental conditions.

PMID- 19749964
TI  - 15-THz pulse generation arising from modulation instability oscillation in a
      colliding-pulse mode-locking dye laser.
AB  - 15-THz trains of a few-tens-of-femtoseconds optical pulses were generated by
      modulation instability oscillation in a colliding-pulse mode-locked dye laser. A
      repeatable and stable modulation instability regime was obtained with the laser
      operating in the anomalous-dispersion regime and with a low saturable-absorber
      concentration. Autocorrelation measurements indicate that subpulses were
      completely separated in real time. Variations of the modulation with the pump
      power and the amount of dispersion in the cavity are in good agreement with
      modulation instability theory.

PMID- 19749965
TI  - Amplification and compression of weak picosecond optical pulses by using
      semiconductor-laser amplifiers.
AB  - A novel pulse-compression scheme is proposed and demonstrated for compressing
      weak picosecond pulses having energies as small as 0.1 pJ. A semiconductor-laser
      amplifier is shown to impose a nearlylinear frequency chirp on the pulse as a
      result of self-phase modulation occurring because of gain-saturation-induced
      index changes. The amplified chirped pulse can be compressed by passing it
      through a dispersive delay line. The theory shows that, depending on the
      operating conditions, the pulse width can be reduced by a factor of ~2-4 and the
      peak power can be enhanced by a factor of ~10-100. The preliminary experimental
      results are in agreement with theory.

PMID- 19749966
TI  - Generation and detection of a monolayer grating by laser desorption and second
      harmonic generation: CO on Ni(111).
AB  - We show that a monolayer grating of CO on Ni(111) can be generated by laser
      desorption using two interfering laser pulses and detected and characterized in
      situ by surface second-harmonic generation.

PMID- 19749967
TI  - Multiphoton resonances in the modulated fluorescence from an inhomogeneously
      broadened medium.
AB  - We consider the interaction of a fully amplitude-modulated, narrow-band laser
      with a strongly inhomogeneously broadened two-level medium and show that
      harmonics of the fluorescence of susceptibility, unlike the time-averaged
      fluorescence, retain the characteristic multiphoton resonance structure that is
      found in the absence of inhomogeneous broadening. This behavior correlates with
      the existence of double branches of the corresponding Bloch-Siegert resonance
      curves. For strong fields, the depth of modulation and the phase shift of the
      lowest fluorescence harmonic may deviate significantly from the results for weak,
      broadband excitation.

PMID- 19749968
TI  - Bistable holes in nonlinear optical fibers.
AB  - Bistable dark solitary-wave solutions (bistable holes) to the generalized
      nonlinear Schrodinger equation are shown to exist in the normal dispersion regime
      for nonlinearities that are Kerr-like at low intensities, rise sufficiently
      rapidly at intermediate intensities, and become Kerr-like again or approach a
      constant value at large intensities. The bistable nature and soliton character of
      the holes are confirmed through numerical switching simulations. The concept of
      asymptotic pinning (of the x-dependent part) of the phase is used to explain the
      resultant velocities of the output solitons and the observed asymmetry in the
      emitted radiation.

PMID- 19749969
TI  - Effects of modulational instability on coherent transmission systems.
AB  - The modulational instability of light waves in fibers with anomalous dispersion
      produces growth of initial sidebands generated in coherent transmission systems.
      Since the growth rate is proportional to the carrier intensity, the repeated
      amplification of the carrier degrades the signal-to-noise ratio in proportion to
      the product of the number of amplifications and the initial carrier intensity.
      With nominal parameters in a system of a few milliwatts of power, the e folding
      distance of the signal-to-noise ratio becomes of the order of a few hundred
      kilometers.

PMID- 19749970
TI  - Suppression and manipulation of the soliton self-frequency shift.
AB  - Direct experimental evidence is presented that shows that in the presence of
      bandwidth-limited amplification, specifically, stimulated Raman scattering in a
      single-mode silica fiber, the self-frequency-shifting effect exhibited by
      solitons can be effectively suppressed.

PMID- 19749971
TI  - Nonlinear fiber couplers: switches and polarization beam splitters.
AB  - Propagation in a nonlinear coupler at a specified input power is like that in a
      linear coupler with a specified but nonsinusoidal periodic refractive index. This
      suggests novel schemes for reducing the switching power and leads to simple
      analytical expressions for ideal switches and for power-sensitive polarization
      beam splitters. Most importantly, we show that the critical power is reduced
      significantly by "freezing" a nonsinusoidal refractive index into the basic
      linear structure that mimics the nonlinear index above the critical power, thus
      biasing the nonlinear coupler.

PMID- 19749972
TI  - Polarization mode coupling in highly birefringent optical-fiber ring resonators.
AB  - The transmission characteristics of a polarization-maintaining optical-fiber ring
      resonator are examined. The resonator's response is found to be strongly
      dependent on the differential phase delay between the fiber birefringence axes.
      Large cross talk of as much as 40% between the fiber modes and splitting of the
      resonance notch can occur, even for very good (better than -35-dB) isolation
      between the fiber polarization modes.

PMID- 19749973
TI  - Measurement of polarization-mode dispersion in single-mode fibers with random
      mode coupling.
AB  - A simple frequency-domain technique for measuring polarization-mode dispersion in
      single-mode fibers with random mode coupling is used to give what is to my
      knowledge the first direct experimental demonstration of the transition of the
      dispersion from a linear length dependence to a square-root-of-length dependence.
      Sensitivity to external perturbations is demonstrated by an order-of-magnitude
      increase in dispersion when the fiber is removed from a conventional spool and
      placed on a large-diameter drum. An expression for the length-dependent
      probability density function that describes the dispersion for highly coherent
      sources is also presented and confirmed experimentally.

PMID- 19749974
TI  - Optical pulse modeling with Hermite-Gaussian functions.
AB  - An asymptotic method for synthesis and analysis of optical pulses using Hermite
      Gaussian functions is outlined. This enables distortion of arbitrary pulse
      waveforms in monomode fibers to be studied analytically, even with chirping of
      the light source. This pulse-modeling technique is proposed to be particularly
      suitable for the synthesis of analytically tractable representations of realistic
      pulse shapes, providing a flexible and effective platform for analytic system
      optimization.

PMID- 19749975
TI  - Hybrid TE-TM nonlinear guided waves.
AB  - The first integral of the complete set of Maxwell's equations coupled through
      intrinsic nonlinearities in Kerr-type media has been found. The application of
      this result to wave propagation along a nonlinear optical waveguide leads to a
      general dispersion relation for nonlinear surface and guided waves of arbitrary
      polarization, i.e., hybrid TE-TM waves.

PMID- 19749976
TI  - Picosecond pump-probe interferometric measurement of optical nonlinearities in
      channel waveguides.
AB  - An interferometric technique for measuring with picosecond resolution the time
      evolution of the real and imaginary components of optical nonlinearities in
      channel waveguides is described. Characteristics of the technique are illustrated
      with measurements of band-filling optical nonlinearities in CdS(x)Se(1-x)-doped
      glass channel waveguides.

PMID- 19749977
TI  - A Systematic Approach for Computing Zero-Point Energy, Quantum Partition
      Function, and Tunneling Effect Based on Kleinert's Variational Perturbation
      Theory.
AB  - In this paper, we describe an automated integration-free path-integral (AIF-PI)
      method, based on Kleinert's variational perturbation (KP) theory, to treat
      internuclear quantum-statistical effects in molecular systems. We have developed
      an analytical method to obtain the centroid potential as a function of the
      variational parameter in the KP theory, which avoids numerical difficulties in
      path-integral Monte Carlo or molecular dynamics simulations, especially at the
      limit of zero-temperature. Consequently, the variational calculations using the
      KP theory can be efficiently carried out beyond the first order, i.e., the
      Giachetti-Tognetti-Feynman-Kleinert variational approach, for realistic chemical
      applications. By making use of the approximation of independent instantaneous
      normal modes (INM), the AIF-PI method can readily be applied to many-body
      systems. Previously, we have shown that in the INM approximation, the AIF-PI
      method is accurate for computing the quantum partition function of a water
      molecule (3 degrees of freedom) and the quantum correction factor for the
      collinear H(3) reaction rate (2 degrees of freedom). In this work, the accuracy
      and properties of the KP theory are further investigated by using the first three
      order perturbations on an asymmetric double-well potential, the bond vibrations
      of H(2), HF, and HCl represented by the Morse potential, and a proton-transfer
      barrier modeled by the Eckart potential. The zero-point energy, quantum partition
      function, and tunneling factor for these systems have been determined and are
      found to be in excellent agreement with the exact quantum results. Using our new
      analytical results at the zero-temperature limit, we show that the minimum value
      of the computed centroid potential in the KP theory is in excellent agreement
      with the ground state energy (zero-point energy) and the position of the centroid
      potential minimum is the expectation value of particle position in wave
      mechanics. The fast convergent property of the KP theory is further examined in
      comparison with results from the traditional Rayleigh-Ritz variational approach
      and Rayleigh-Schrodinger perturbation theory in wave mechanics. The present
      method can be used for thermodynamic and quantum dynamic calculations, including
      to systematically determine the exact value of zero-point energy and to study
      kinetic isotope effects for chemical reactions in solution and in enzymes.

PMID- 19749978
TI  - Species tree inference by minimizing deep coalescences.
AB  - In a 1997 seminal paper, W. Maddison proposed minimizing deep coalescences, or
      MDC, as an optimization criterion for inferring the species tree from a set of
      incongruent gene trees, assuming the incongruence is exclusively due to lineage
      sorting. In a subsequent paper, Maddison and Knowles provided and implemented a
      search heuristic for optimizing the MDC criterion, given a set of gene trees.
      However, the heuristic is not guaranteed to compute optimal solutions, and its
      hill-climbing search makes it slow in practice. In this paper, we provide two
      exact solutions to the problem of inferring the species tree from a set of gene
      trees under the MDC criterion. In other words, our solutions are guaranteed to
      find the tree that minimizes the total number of deep coalescences from a set of
      gene trees. One solution is based on a novel integer linear programming (ILP)
      formulation, and another is based on a simple dynamic programming (DP) approach.
      Powerful ILP solvers, such as CPLEX, make the first solution appealing,
      particularly for very large-scale instances of the problem, whereas the DP-based
      solution eliminates dependence on proprietary tools, and its simplicity makes it
      easy to integrate with other genomic events that may cause gene tree
      incongruence. Using the exact solutions, we analyze a data set of 106 loci from
      eight yeast species, a data set of 268 loci from eight Apicomplexan species, and
      several simulated data sets. We show that the MDC criterion provides very
      accurate estimates of the species tree topologies, and that our solutions are
      very fast, thus allowing for the accurate analysis of genome-scale data sets.
      Further, the efficiency of the solutions allow for quick exploration of sub
      optimal solutions, which is important for a parsimony-based criterion such as
      MDC, as we show. We show that searching for the species tree in the compatibility
      graph of the clusters induced by the gene trees may be sufficient in practice, a
      finding that helps ameliorate the computational requirements of optimization
      solutions. Further, we study the statistical consistency and convergence rate of
      the MDC criterion, as well as its optimality in inferring the species tree.
      Finally, we show how our solutions can be used to identify potential horizontal
      gene transfer events that may have caused some of the incongruence in the data,
      thus augmenting Maddison's original framework. We have implemented our solutions
      in the PhyloNet software package, which is freely available at:
      http://bioinfo.cs.rice.edu/phylonet.

PMID- 19749979
TI  - A transcription elongation factor that links signals from the reproductive system
      to lifespan extension in Caenorhabditis elegans.
AB  - In Caenorhabditis elegans and Drosophila melanogaster, the aging of the soma is
      influenced by the germline. When germline-stem cells are removed, aging slows and
      lifespan is increased. The mechanism by which somatic tissues respond to loss of
      the germline is not well-understood. Surprisingly, we have found that a predicted
      transcription elongation factor, TCER-1, plays a key role in this process. TCER-1
      is required for loss of the germ cells to increase C. elegans' lifespan, and it
      acts as a regulatory switch in the pathway. When the germ cells are removed, the
      levels of TCER-1 rise in somatic tissues. This increase is sufficient to trigger
      key downstream events, as overexpression of tcer-1 extends the lifespan of normal
      animals that have an intact reproductive system. Our findings suggest that TCER-1
      extends lifespan by promoting the expression of a set of genes regulated by the
      conserved, life-extending transcription factor DAF-16/FOXO. Interestingly, TCER-1
      is not required for DAF-16/FOXO to extend lifespan in animals with reduced
      insulin/IGF-1 signaling. Thus, TCER-1 specifically links the activity of a
      broadly deployed transcription factor, DAF-16/FOXO, to longevity signals from
      reproductive tissues.

PMID- 19749980
TI  - A role for E2F activities in determining the fate of Myc-induced lymphomagenesis.
AB  - The phenotypic heterogeneity that characterizes human cancers reflects the
      enormous genetic complexity of the oncogenic process. This complexity can also be
      seen in mouse models where it is frequently observed that in addition to the
      initiating genetic alteration, the resulting tumor harbors additional,
      somatically acquired mutations that affect the tumor phenotype. To investigate
      the role of genetic interactions in the development of tumors, we have made use
      of the Emu-myc model of pre-B and B cell lymphoma. Since various studies point to
      a functional interaction between Myc and the Rb/E2F pathway, we have investigated
      the role of E2F activities in the process of Myc-induced lymphomagenesis. Whereas
      the absence of E2F1 and E2F3 function has no impact on Myc-mediated tumor
      development, the absence of E2F2 substantially accelerates the time of tumor
      onset. Conversely, tumor development is delayed by the absence of E2F4. The
      enhanced early onset of tumors seen in the absence of E2F2 coincides with an
      expansion of immature B lineage cells that are likely to be the target for Myc
      oncogenesis. In contrast, the absence of E2F4 mutes the response of the lineage
      to Myc and there is no expansion of immature B lineage cells. We also find that
      distinct types of tumors emerge from the Emu-myc mice, distinguished by different
      patterns of gene expression, and that the relative proportions of these tumor
      types are affected by the absence of either E2F2 or E2F4. From these results, we
      conclude that there are several populations of tumors that arise from the Emu-myc
      model, reflecting distinct populations of cells that are susceptible to Myc
      mediated oncogenesis and that the proportion of these cell populations is
      affected by the presence or absence of E2F activities.

PMID- 19749981
TI  - The evolutionary origin of man can be traced in the layers of defunct ancestral
      alpha satellites flanking the active centromeres of human chromosomes.
AB  - Alpha satellite domains that currently function as centromeres of human
      chromosomes are flanked by layers of older alpha satellite, thought to contain
      dead centromeres of primate progenitors, which lost their function and the
      ability to homogenize satellite repeats, upon appearance of a new centromere.
      Using cladistic analysis of alpha satellite monomers, we elucidated complete
      layer patterns on chromosomes 8, 17, and X and related them to each other and to
      primate alpha satellites. We show that discrete and chronologically ordered alpha
      satellite layers are partially symmetrical around an active centromere and their
      succession is partially shared in non-homologous chromosomes. The layer structure
      forms a visual representation of the human evolutionary lineage with layers
      corresponding to ancestors of living primates and to entirely fossil taxa.
      Surprisingly, phylogenetic comparisons suggest that alpha satellite arrays went
      through periods of unusual hypermutability after they became "dead" centromeres.
      The layer structure supports a model of centromere evolution where new variants
      of a satellite repeat expanded periodically in the genome by rounds of inter
      chromosomal transfer/amplification. Each wave of expansion covered all or many
      chromosomes and corresponded to a new primate taxon. Complete elucidation of the
      alpha satellite phylogenetic record would give a unique opportunity to number and
      locate the positions of major extinct taxa in relation to human ancestors shared
      with extant primates. If applicable to other satellites in non-primate taxa,
      analysis of centromeric layers could become an invaluable tool for phylogenetic
      studies.

PMID- 19749983
TI  - American heart association, 2007 scientific sessions.

PMID- 19749982
TI  - Eradication of chronic myeloid leukemia stem cells: a novel mathematical model
      predicts no therapeutic benefit of adding G-CSF to imatinib.
AB  - Imatinib mesylate induces complete cytogenetic responses in patients with chronic
      myeloid leukemia (CML), yet many patients have detectable BCR-ABL transcripts in
      peripheral blood even after prolonged therapy. Bone marrow studies have shown
      that this residual disease resides within the stem cell compartment. Quiescence
      of leukemic stem cells has been suggested as a mechanism conferring insensitivity
      to imatinib, and exposure to the Granulocyte-Colony Stimulating Factor (G-CSF),
      together with imatinib, has led to a significant reduction in leukemic stem cells
      in vitro. In this paper, we design a novel mathematical model of stem cell
      quiescence to investigate the treatment response to imatinib and G-CSF. We find
      that the addition of G-CSF to an imatinib treatment protocol leads to observable
      effects only if the majority of leukemic stem cells are quiescent; otherwise it
      does not modulate the leukemic cell burden. The latter scenario is in agreement
      with clinical findings in a pilot study administering imatinib continuously or
      intermittently, with or without G-CSF (GIMI trial). Furthermore, our model
      predicts that the addition of G-CSF leads to a higher risk of resistance since it
      increases the production of cycling leukemic stem cells. Although the pilot study
      did not include enough patients to draw any conclusion with statistical
      significance, there were more cases of progression in the experimental arms as
      compared to continuous imatinib. Our results suggest that the additional use of G
      CSF may be detrimental to patients in the clinic.

PMID- 19749984
TI  - New drugs drug news.

PMID- 19749985
TI  - Pharmaceutical approval update.

PMID- 19749986
TI  - Dalbavancin (zeven), a novel glycopeptide for resistant gram-positive organisms.

PMID- 19749987
TI  - FDA Considers New Avenue For Pharmacist Reimbursement: Customers Must Consult
      with Pharmacists To Buy Behind-the-Counter Drugs.

PMID- 19749989
TI  - Better.

PMID- 19749988
TI  - Aripiprazole (abilify) and tardive dyskinesia.
AB  - Second-generation (atypical) antipsychotic agents are being used within their
      indications as well as widely off-label because of their lower risk of causing
      extrapyramidal symptoms and tardive dyskinesia (TD). The risk of metabolic
      disorders has taken over much of clinical practice and the current literature on
      adverse effects. In this brief article, we discuss a case of TD that developed
      after a patient used aripiprazole as off-label augmentation for treatment
      resistant depression. We emphasize the fact that TD is an adverse effect that
      must still be monitored.

PMID- 19749990
TI  - Advances in vaccine technology and their impact on managed care.
AB  - The discovery of vaccines has led to the near eradication of several important
      diseases and has had a tremendous impact on health for a relatively low cost.
      However, most vaccines in use today were developed by techniques that were
      pioneered more than 100 years ago and do not represent the full potential of the
      field. The introduction of genetic engineering has fueled rapid advances in
      vaccine technology and is now leading to the entry of new products in the
      marketplace.In the past, options for the utilization of vaccines in the area of
      managed care had been quite limited because of the historically straightforward
      application of immunizations. The growing number and type of vaccine targets,
      coupled with novel, more effective formulations, adjuvants, and routes of
      delivery for vaccines, will undoubtedly create new challenges. Although progress
      in vaccine technology has the potential to prevent illness and reduce the
      economic burden of diseases in the long term, thereby improving outcomes, ongoing
      problems remain in the short term.Who should and will pay for these anticipated
      improvements in health?How will this period of change be managed?This article
      describes the present "vaccine revolution" and attempts to answer these
      questions, which are becoming increasingly important in managed care.

PMID- 19749991
TI  - Impact of bipolar disorder on the family: utilization and cost of health care
      resources.
AB  - OBJECTIVE: Our retrospective analysis compared costs and patterns of health care
      utilization by families that included a member with bipolar disorder ("bipolar
      families") and by families without serious psychiatric disease ("control
      families"). METHODS: We used the MarketScan Commercial Claims and Encounters
      Database covering January 1998 through December 2002. International
      Classification of Diseases (ICD-9-CM) codes were used to identify individuals
      with bipolar disorder and link them to their family members. Bipolar families
      were matched in a ratio of 1:3 to families without a serious mental illness. We
      calculated and statistically compared the mean annual use of resources and health
      care costs for each group, including the individual with bipolar disorder. We
      used a multivariate model to test the effect of demographic and health care
      variables on the impact of total health care expenditures. RESULTS: Families with
      a member with bipolar disorder (n = 43,448), compared with matched families (n =
      122,769), made significantly more outpatient physician visits (24 vs. eight; P <
      0.001), more inpatient hospital stays (1 vs. 0.3; P < 0.001), and more
      prescription medications (24 vs. 7.8; P < 0.001). Total annual health care costs
      were more than three-fold higher for bipolar families ($4,664), compared with
      matched families ($1,376) (P < 0.001). The multivariate model controlled for
      family size and comorbidities, indicating significantly higher total health care
      costs for families with one or more persons with bipolar disorder than for
      matched families without serious mental illness. CONCLUSION: These results
      indicate that bipolar disorder has a significant financial impact on families in
      addition to the individual with the diagnosis.

PMID- 19749992
TI  - Safety and patient-controlled analgesia: part 2: how to prevent errors.

PMID- 19749994
TI  - Health 3.0.

PMID- 19749993
TI  - Aliskiren (tekturna), a novel antihypertensive approach to inhibition of the
      Renin-Angiotensin-aldosterone system.

PMID- 19749996
TI  - New drugs drug news.

PMID- 19749995
TI  - Evaluation of the Management of Acute Venous Thromboembolism and Its Outcomes:
      One Institution's Experience.
AB  - BACKGROUND: There is often a divergence between standardized practice guidelines
      and actual practice. Such deviations can result in adverse outcomes. In addition,
      studies that identify independent risk factors associated with bleeding or
      recurrent venous thromboembolism (VTE) are often limited. OBJECTIVE: We sought to
      evaluate the appropriateness of VTE management at our Veterans Affairs facility
      in Fargo and to identify independent patient characteristics or treatments that
      were associated with recurrence of VTE or major bleeding. METHODS: We performed a
      retrospective chart review of patients admitted for deep vein thrombosis (DVT)
      and/or pulmonary embolism (PE). RESULTS: Of the patients who were given
      enoxaparin, 96% received an appropriate dose; however, of the patients receiving
      unfractionated heparin, only 54.7% received an appropriate initial dose. The
      International Normalized Ratio (INR) was below 1.9 in 19.3% of patients when
      heparin was stopped, unknown in 12.7%, and 1.9 or higher in 68%. Thirty-two
      patients (21.3%) continued to take warfarin for three months or less, and 13 of
      these patients (41%) were treated for an idiopathic VTE. Forty-eight patients
      (57%) being treated for VTE for the first time continued with warfarin for more
      than six months. Twenty-one patients (14%) were started on 10 mg of warfarin
      daily; 40% received heparin for less than five days. The only significant
      difference between the bleeding and non-bleeding groups was an INR above 3 at the
      time of the bleeding episode (P < 0.0001). CONCLUSION: We learned that the
      management of VTE at our institution diverged from standardized practice
      guidelines. Larger randomized, prospective studies are needed to identify
      independent risk factors for major bleeding or recurrence of VTE and their
      correlation with patient outcomes.

PMID- 19749997
TI  - Adding Lidocaine to IV Potassium Infusions Can Cause Safety Problems.

PMID- 19749998
TI  - The language of (forgive us) change, as p&t enters the digital age.

PMID- 19749999
TI  - American society of hematology 49th annual meeting.

PMID- 19750001
TI  - Pharmaceutical approval update.

PMID- 19750000
TI  - Use and outcomes of antifibrinolytic therapy in patients undergoing
      cardiothoracic surgery at 20 academic medical centers in the United States.
AB  - BACKGROUND: Several clinical trials have shown an association between the use of
      aprotinin in cardiothoracic surgery (CTS) patients and an increased risk of
      adverse renal, cardiovascular, and cerebrovascular events. Other antifibrinolytic
      agents-aminocaproic acid (AA) and tranexamic acid (TA)-have not shown elevated
      risks. Using a large administrative data set, we sought to examine these
      findings. METHODS: In our observational database study of CTS patients who were
      discharged from 20 academic medical centers from October 2002 through September
      2005, we assessed the use of antifibrinolytic therapy on select patient outcomes
      using descriptive and inferential statistics to compare the various groups.
      RESULTS: For the CTS patients, AA was used in 9,751 (15.5% of patients) and
      aprotinin was used in 6,855 (10.9% of patients). Only 17 patients from four
      hospitals received TA; therefore, TA was excluded from further analysis. A
      quarterly analysis showed a slow decline in the use of AA, with a gradual
      increase in the use of aprotinin over the study time period. Variation by
      hospital using each option was considerable (range, 0%-50%). Statistically
      significant differences in mortality rates (P < 0.001) occurred with AA (2.6%),
      aprotinin (5.2%), and control patients (n = 46,123), who did not use any
      antifibrinolytic agents (3.9%). Rates of acute renal failure were 6.2% with AA,
      10.9% with aprotinin, and 6.1% in controls; hemodialysis rates were 2.8%, 6.4%,
      and 2.6%, respectively. Postoperative acute myocardial infarction occurred in
      only two cases of patients receiving AA, in none of those using aprotinin, and in
      63 controls. CONCLUSION: Although the use of aprotinin has been increasing,
      compared with AA, the overall use of antifibrinolytic agents in patients
      undergoing CTS has remained relatively stable over a three-year period, at under
      30%. Significant differences in patient outcomes were observed between the two
      treatment groups. Given the growing body of evidence for the use of
      antifibrinolytic therapy, hospitals might be best served by examining existing
      patterns of use and by instituting restrictions of aprotinin for patients facing
      an increased risk for bleeding during CTS.

PMID- 19750002
TI  - Off-label drug promotion now on the table: house and senate voice concerns.

PMID- 19750003
TI  - Evaluation of objective uncertainty in the visual system.
AB  - The role of sensory systems is to provide an organism with information about its
      environment. Because sensory information is noisy and insufficient to uniquely
      determine the environment, natural perceptual systems have to cope with
      systematic uncertainty. The extent of that uncertainty is often crucial to the
      organism: for instance, in judging the potential threat in a stimulus. Inducing
      uncertainty by using visual noise, we had human observers perform a task where
      they could improve their performance by choosing the less uncertain among pairs
      of visual stimuli. Results show that observers had access to a reliable measure
      of visual uncertainty in their decision-making, showing that subjective
      uncertainty in this case is connected to objective uncertainty. Based on a
      Bayesian model of the task, we discuss plausible computational schemes for that
      ability.

PMID- 19750004
TI  - A systems genetics approach implicates USF1, FADS3, and other causal candidate
      genes for familial combined hyperlipidemia.
AB  - We hypothesized that a common SNP in the 3' untranslated region of the upstream
      transcription factor 1 (USF1), rs3737787, may affect lipid traits by influencing
      gene expression levels, and we investigated this possibility utilizing the
      Mexican population, which has a high predisposition to dyslipidemia. We first
      associated rs3737787 genotypes in Mexican Familial Combined Hyperlipidemia (FCHL)
      case/control fat biopsies, with global expression patterns. To identify sets of
      co-expressed genes co-regulated by similar factors such as transcription factors,
      genetic variants, or environmental effects, we utilized weighted gene co
      expression network analysis (WGCNA). Through WGCNA in the Mexican FCHL fat
      biopsies we identified two significant Triglyceride (TG)-associated co-expression
      modules. One of these modules was also associated with FCHL, the other FCHL
      component traits, and rs3737787 genotypes. This USF1-regulated FCHL-associated
      (URFA) module was enriched for genes involved in lipid metabolic processes. Using
      systems genetics procedures we identified 18 causal candidate genes in the URFA
      module. The FCHL causal candidate gene fatty acid desaturase 3 (FADS3) was
      associated with TGs in a recent Caucasian genome-wide significant association
      study and we replicated this association in Mexican FCHL families. Based on a
      USF1-regulated FCHL-associated co-expression module and SNP rs3737787, we
      identify a set of causal candidate genes for FCHL-related traits. We then provide
      evidence from two independent datasets supporting FADS3 as a causal gene for FCHL
      and elevated TGs in Mexicans.

PMID- 19750005
TI  - Transcriptional regulation of PP2A-A alpha is mediated by multiple factors
      including AP-2alpha, CREB, ETS-1, and SP-1.
AB  - Protein phosphatases-2A (PP-2A) is a major serine/threonine phosphatase and
      accounts for more than 50% serine/threonine phosphatase activity in eukaryotes.
      The holoenzyme of PP-2A consists of the scaffold A subunit, the catalytic C
      subunit and the regulatory B subunit. The scaffold subunits, PP2A-A alpha/beta,
      provide a platform for both C and B subunits to bind, thus playing a crucial role
      in providing specific PP-2A activity. Mutation of the two genes encoding PP2A-A
      alpha/beta leads to carcinogenesis and likely other human diseases. Regulation of
      these genes by various factors, both extracellular and intracellular, remains
      largely unknown. In the present study, we have conducted functional dissection of
      the promoter of the mouse PP2A-A alpha gene. Our results demonstrate that the
      proximal promoter of the mouse PP2A-A alpha gene contains numerous cis-elements
      for the binding of CREB, ETS-1, AP-2 alpha, SP-1 besides the putative TFIIB
      binding site (BRE) and the downstream promoter element (DPE). Gel mobility
      shifting assays revealed that CREB, ETS-1, AP-2 alpha, and SP-1 all bind to PP2A
      A alpha gene promoter. In vitro mutagenesis and reporter gene activity assays
      reveal that while SP-1 displays negative regulation, CREB, ETS-1 and AP-2A alpha
      all positively regulate the promoter of the PP2A-A alpha gene. ChIP assays
      further confirm that all the above transcription factors participate the
      regulation of PP2A-A alpha gene promoter. Together, our results reveal that
      multiple transcription factors regulate the PP2A-A alpha gene.

PMID- 19750006
TI  - Gene expression patterns in peripheral blood correlate with the extent of
      coronary artery disease.
AB  - Systemic and local inflammation plays a prominent role in the pathogenesis of
      atherosclerotic coronary artery disease, but the relationship of whole blood gene
      expression changes with coronary disease remains unclear. We have investigated
      whether gene expression patterns in peripheral blood correlate with the severity
      of coronary disease and whether these patterns correlate with the extent of
      atherosclerosis in the vascular wall. Patients were selected according to their
      coronary artery disease index (CADi), a validated angiographical measure of the
      extent of coronary atherosclerosis that correlates with outcome. RNA was
      extracted from blood of 120 patients with at least a stenosis greater than 50%
      (CADi > or = 23) and from 121 controls without evidence of coronary stenosis
      (CADi = 0). 160 individual genes were found to correlate with CADi (rho > 0.2,
      P<0.003). Prominent differential expression was observed especially in genes
      involved in cell growth, apoptosis and inflammation. Using these 160 genes, a
      partial least squares multivariate regression model resulted in a highly
      predictive model (r(2) = 0.776, P<0.0001). The expression pattern of these 160
      genes in aortic tissue also predicted the severity of atherosclerosis in human
      aortas, showing that peripheral blood gene expression associated with coronary
      atherosclerosis mirrors gene expression changes in atherosclerotic arteries. In
      conclusion, the simultaneous expression pattern of 160 genes in whole blood
      correlates with the severity of coronary artery disease and mirrors expression
      changes in the atherosclerotic vascular wall.

PMID- 19750007
TI  - Identification of gemin5 as a novel 7-methylguanosine cap-binding protein.
AB  - BACKGROUND: A unique attribute of RNA molecules synthesized by RNA polymerase II
      is the presence of a 7-methylguanosine (m(7)G) cap structure added co
      transcriptionally to the 5' end. Through its association with trans-acting
      effector proteins, the m(7)G cap participates in multiple aspects of RNA
      metabolism including localization, translation and decay. However, at present
      relatively few eukaryotic proteins have been identified as factors capable of
      direct association with m(7)G. METHODOLOGY/PRINCIPAL FINDINGS: Employing an
      unbiased proteomic approach, we identified gemin5, a component of the survival of
      motor neuron (SMN) complex, as a factor capable of direct and specific
      interaction with the m(7)G cap. Gemin5 was readily purified by cap-affinity
      chromatography in contrast to other SMN complex proteins. Investigating the
      underlying basis for this observation, we found that purified gemin5 associates
      with m(7)G-linked sepharose in the absence of detectable eIF4E, and specifically
      crosslinks to radiolabeled cap structure after UV irradiation. Deletion analysis
      revealed that an intact set of WD repeat domains located in the N-terminal half
      of gemin5 are required for cap-binding. Moreover, using structural modeling and
      site-directed mutagenesis, we identified two proximal aromatic residues located
      within the WD repeat region that significantly impact m(7)G association.
      CONCLUSIONS/SIGNIFICANCE: This study rigorously identifies gemin5 as a novel cap
      binding protein and describes an unprecedented role for WD repeat domains in
      m(7)G recognition. The findings presented here will facilitate understanding of
      gemin5's role in the metabolism of non-coding snRNAs and perhaps other RNA pol II
      transcripts.

PMID- 19750008
TI  - High-density microwell chip for culture and analysis of stem cells.
AB  - With recent findings on the role of reprogramming factors on stem cells, in vitro
      screening assays for studying (de)-differentiation is of great interest. We
      developed a miniaturized stem cell screening chip that is easily accessible and
      provides means of rapidly studying thousands of individual stem/progenitor cell
      samples, using low reagent volumes. For example, screening of 700,000 substances
      would take less than two days, using this platform combined with a conventional
      bio-imaging system. The microwell chip has standard slide format and consists of
      672 wells in total. Each well holds 500 nl, a volume small enough to drastically
      decrease reagent costs but large enough to allow utilization of standard
      laboratory equipment. Results presented here include weeklong culturing and
      differentiation assays of mouse embryonic stem cells, mouse adult neural stem
      cells, and human embryonic stem cells. The possibility to either maintain the
      cells as stem/progenitor cells or to study cell differentiation of
      stem/progenitor cells over time is demonstrated. Clonality is critical for stem
      cell research, and was accomplished in the microwell chips by isolation and
      clonal analysis of single mouse embryonic stem cells using flow cytometric cell
      sorting. Protocols for practical handling of the microwell chips are presented,
      describing a rapid and user-friendly method for the simultaneous study of
      thousands of stem cell cultures in small microwells. This microwell chip has high
      potential for a wide range of applications, for example directed differentiation
      assays and screening of reprogramming factors, opening up considerable
      opportunities in the stem cell field.

PMID- 19750009
TI  - Distinct gene number-genome size relationships for eukaryotes and non-eukaryotes:
      gene content estimation for dinoflagellate genomes.
AB  - The ability to predict gene content is highly desirable for characterization of
      not-yet sequenced genomes like those of dinoflagellates. Using data from
      completely sequenced and annotated genomes from phylogenetically diverse
      lineages, we investigated the relationship between gene content and genome size
      using regression analyses. Distinct relationships between log(10)-transformed
      protein-coding gene number (Y') versus log(10)-transformed genome size (X',
      genome size in kbp) were found for eukaryotes and non-eukaryotes. Eukaryotes best
      fit a logarithmic model, Y' = ln(-46.200+22.678X', whereas non-eukaryotes a
      linear model, Y' = 0.045+0.977X', both with high significance (p<0.001,
      R(2)>0.91). Total gene number shows similar trends in both groups to their
      respective protein coding regressions. The distinct correlations reflect lower
      and decreasing gene-coding percentages as genome size increases in eukaryotes
      (82%-1%) compared to higher and relatively stable percentages in prokaryotes and
      viruses (97%-47%). The eukaryotic regression models project that the smallest
      dinoflagellate genome (3x10(6) kbp) contains 38,188 protein-coding (40,086 total)
      genes and the largest (245x10(6) kbp) 87,688 protein-coding (92,013 total) genes,
      corresponding to 1.8% and 0.05% gene-coding percentages. These estimates do not
      likely represent extraordinarily high functional diversity of the encoded
      proteome but rather highly redundant genomes as evidenced by high gene copy
      numbers documented for various dinoflagellate species.

PMID- 19750010
TI  - O antigen allows B. parapertussis to evade B. pertussis vaccine-induced immunity
      by blocking binding and functions of cross-reactive antibodies.
AB  - Although the prevalence of Bordetella parapertussis varies dramatically among
      studies in different populations with different vaccination regimens, there is
      broad agreement that whooping cough vaccines, composed only of B. pertussis
      antigens, provide little if any protection against B. parapertussis. In C57BL/6
      mice, a B. pertussis whole-cell vaccine (wP) provided modest protection against
      B. parapertussis, which was dependent on IFN-gamma. The wP was much more
      protective against an isogenic B. parapertussis strain lacking O-antigen than its
      wild-type counterpart. O-antigen inhibited binding of wP-induced antibodies to B.
      parapertussis, as well as antibody-mediated opsonophagocytosis in vitro and
      clearance in vivo. aP-induced antibodies also bound better in vitro to the O
      antigen mutant than to wild-type B. parapertussis, but aP failed to confer
      protection against wild-type or O antigen-deficient B. parapertussis in mice.
      Interestingly, B. parapertussis-specific antibodies provided in addition to
      either wP or aP were sufficient to very rapidly reduce B. parapertussis numbers
      in mouse lungs. This study identifies a mechanism by which one pathogen escapes
      immunity induced by vaccination against a closely related pathogen and may
      explain why B. parapertussis prevalence varies substantially between populations
      with different vaccination strategies.

PMID- 19750011
TI  - Mortality after hospitalization for pneumonia among individuals with HIV, 1995
      2008: a Danish cohort study.
AB  - BACKGROUND: HIV-infected persons are at increased risk of pneumonia, even with
      highly active antiretroviral treatment (HAART). We examined the impact of
      pneumonia on mortality and identified prognostic factors for death among HIV
      infected. METHODOLOGY/PRINCIPAL FINDINGS: In a nationwide, population-based
      cohort of individuals with HIV, we included persons hospitalized with pneumonia
      from the Danish National Hospital Registry and obtained mortality data from the
      Danish Civil Registration System. Comparing individuals with and without
      pneumonia, we used Poisson regression to estimate relative mortality and logistic
      regression to examine prognostic factors for death following pneumonia. From
      January 1, 1995, to July 1, 2008, we observed 699 episodes of first
      hospitalization for pneumonia among 4,352 HIV patients. Ninety-day mortality
      after pneumonia decreased from 22.4% (95% confidence interval [CI]: 16.5%-28.9%)
      in 1995-1996 to 8.4% (95% CI: 6.1%-11.6%) in 2000-2008. Mortality remained
      elevated for more than a year after hospitalization for pneumonia: adjusted
      mortality rate ratio 5.38 (95% CI: 4.27-6.78), 1.80 (95% CI: 1.36-2.37), and 1.62
      (95% CI: 1.32-2.00) for days 0-90, 91-365, and 366+, respectively. The following
      variables predicted mortality within 90 days following hospitalization for
      pneumonia (adjusted Odds Ratios): male sex (3.77, 95% CI: 1.37-10.4), Charlson
      Comorbidity Index score > or = 2 (3.86, 95% CI: 2.19-6.78); no current HAART
      (3.58, 95% CI: 1.83-6.99); history of AIDS (2.46, 95% CI: 1.40-4.32); age per 10
      year increase (1.43, 95% CI: 1.11-1.85); and CD4+ cell count < or = 200 (2.52,
      95% CI: 1.37-4.65). CONCLUSIONS/SIGNIFICANCE: The first hospitalization for
      pneumonia among HIV-infected individuals was associated with elevated risk of
      death up to more than a year later. Use of HAART decreased the risk, independent
      of current CD4+ cell count. Prognosis following pneumonia improved over calendar
      time.

PMID- 19750012
TI  - Identification of antifungal compounds active against Candida albicans using an
      improved high-throughput Caenorhabditis elegans assay.
AB  - Candida albicans, the most common human pathogenic fungus, can establish a
      persistent lethal infection in the intestine of the microscopic nematode
      Caenorhabditis elegans. The C. elegans-C. albicans infection model was previously
      adapted to screen for antifungal compounds. Modifications to this screen have
      been made to facilitate a high-throughput assay including co-inoculation of
      nematodes with C. albicans and instrumentation allowing precise dispensing of
      worms into assay wells, eliminating two labor-intensive steps. This high
      throughput method was utilized to screen a library of 3,228 compounds represented
      by 1,948 bioactive compounds and 1,280 small molecules derived via diversity
      oriented synthesis. Nineteen compounds were identified that conferred an increase
      in C. elegans survival, including most known antifungal compounds within the
      chemical library. In addition to seven clinically used antifungal compounds,
      twelve compounds were identified which are not primarily used as antifungal
      agents, including three immunosuppressive drugs. This assay also allowed the
      assessment of the relative minimal inhibitory concentration, the effective
      concentration in vivo, and the toxicity of the compound in a single assay.

PMID- 19750013
TI  - Exclusion of NFAT5 from mitotic chromatin resets its nucleo-cytoplasmic
      distribution in interphase.
AB  - BACKGROUND: The transcription factor NFAT5 is a major inducer of osmoprotective
      genes and is required to maintain the proliferative capacity of cells exposed to
      hypertonic stress. In response to hypertonicity, NFAT5 translocates to the
      nucleus, binds to regulatory regions of osmoprotective genes and activates their
      transcription. Besides stimulus-specific regulatory mechanisms, the activity of
      transcription factors in cycling cells is also regulated by the passage through
      mitosis, when most transcriptional processes are downregulated. It was not known
      whether mitosis could be a point of control for NFAT5. METHODOLOGY/PRINCIPAL
      FINDINGS: Using confocal microscopy we observed that NFAT5 was excluded from
      chromatin during mitosis in both isotonic and hypertonic conditions. Analysis of
      NFAT5 deletions showed that exclusion was mediated by the carboxy-terminal domain
      (CTD). NFAT5 mutants lacking this domain showed constitutive binding to mitotic
      chromatin independent of tonicity, which caused them to localize in the nucleus
      and remain bound to chromatin in the subsequent interphase without hypertonic
      stimulation. We analyzed the contribution of the CTD, DNA binding, and nuclear
      import and export signals to the subcellular localization of this factor. Our
      results indicated that cytoplasmic localization of NFAT5 in isotonic conditions
      required both the exclusion from mitotic DNA and active nuclear export in
      interphase. Finally, we identified several regions within the CTD of NFAT5, some
      of them overlapping with transactivation domains, which were separately capable
      of causing its exclusion from mitotic chromatin. CONCLUSIONS/SIGNIFICANCE: Our
      results reveal a multipart mechanism regulating the subcellular localization of
      NFAT5. The transactivating module of NFAT5 switches its function from an stimulus
      specific activator of transcription in interphase to an stimulus-independent
      repressor of binding to DNA in mitosis. This mechanism, together with export
      signals acting in interphase, resets the cytoplasmic localization of NFAT5 and
      prevents its nuclear accumulation and association with DNA in the absence of
      hypertonic stress.

PMID- 19750014
TI  - Molecular evolution of the two-component system BvgAS involved in virulence
      regulation in Bordetella.
AB  - The whooping cough agent Bordetella pertussis is closely related to Bordetella
      bronchiseptica, which is responsible for chronic respiratory infections in
      various mammals and is occasionally found in humans, and to Bordetella
      parapertussis, one lineage of which causes mild whooping cough in humans and the
      other ovine respiratory infections. All three species produce similar sets of
      virulence factors that are co-regulated by the two-component system BvgAS. We
      characterized the molecular diversity of BvgAS in Bordetella by sequencing the
      two genes from a large number of diverse isolates. The response regulator BvgA is
      virtually invariant, indicating strong functional constraints. In contrast, the
      multi-domain sensor kinase BvgS has evolved into two different types. The
      pertussis type is found in B. pertussis and in a lineage of essentially human
      associated B. bronchiseptica, while the bronchiseptica type is associated with
      the majority of B. bronchiseptica and both ovine and human B. parapertussis. BvgS
      is monomorphic in B. pertussis, suggesting optimal adaptation or a recent
      population bottleneck. The degree of diversity of the bronchiseptica type BvgS is
      markedly different between domains, indicating distinct evolutionary pressures.
      Thus, absolute conservation of the putative solute-binding cavities of the two
      periplasmic Venus Fly Trap (VFT) domains suggests that common signals are
      perceived in all three species, while the external surfaces of these domains vary
      more extensively. Co-evolution of the surfaces of the two VFT domains in each
      type and domain swapping experiments indicate that signal transduction in the
      periplasmic region may be type-specific. The two distinct evolutionary solutions
      for BvgS confirm that B. pertussis has emerged from a specific B. bronchiseptica
      lineage. The invariant regions of BvgS point to essential parts for its molecular
      mechanism, while the variable regions may indicate adaptations to different
      lifestyles. The repertoire of BvgS sequences will pave the way for functional
      analyses of this prototypic system.

PMID- 19750015
TI  - Interaction of polysialic acid with CCL21 regulates the migratory capacity of
      human dendritic cells.
AB  - Dendritic cells (DCs) are the most potent antigen-presenting cells (APCs).
      Immature DCs (iDCs) are situated in the periphery where they capture pathogen.
      Subsequently, they migrate as mature DCs (mDCs) to draining lymph nodes to
      activate T cells. CCR7 and CCL21 contribute to the migratory capacity of the DC,
      but it is not completely understood what molecular requirements are involved.
      Here we demonstrate that monocyte-derived DCs dramatically change ST8Sia IV
      expression during maturation, leading to the generation of polysialic acid
      (polySia). PolySia expression is highly upregulated after 2 days Toll-like
      receptor-4 (TLR4) triggering. Surprisingly, only immunogenic and not tolerogenic
      mDCs upregulated polySia expression. Furthermore, we show that polySia expression
      on DCs is required for CCL21-directed migration, whereby polySia directly
      captures CCL21. Corresponding to polySia, the expression level of CCR7 is maximal
      two days after TLR4 triggering. In contrast, although TLR agonists other than LPS
      induce upregulation of CCR7, they achieve only a moderate polySia expression. In
      situ we could detect polySia-expressing APCs in the T cell zone of the lymph node
      and in the deep dermis. Together our results indicate that prolonged TLR4
      engagement is required for the generation of polySia-expressing DCs that
      facilitate CCL21 capture and subsequent CCL21-directed migration.

PMID- 19750017
TI  - Early Weight Bearing of Calcaneal Fractures Treated by Intraoperative 3D
      Fluoroscopy and Locked-Screw Plate Fixation.
AB  - Operative therapy of intraarticular fractures of the calcaneus is an established
      surgical standard. The aim is an accurate reduction of the fracture with
      reconstruction of Boehler's angle, length, axis and subtalar joint surface.
      Intraoperative 3D-fluoroscopy with the Siremobil Iso-C 3D(R) mobile C-arm system
      is a valuable assistant for accurate reconstruction of these anatomical
      structures. Remaining incongruities can be recognized and corrected
      intraoperatively. The achieved reduction can be fixed by the advantages of an
      internal fixator (locked-screw plate interface). In the period of October 2002
      until April 2007 we operated 136 patients with intraarticular fractures of the
      calcaneus by means of anatomical reduction, and internal plate fixator under
      intraoperative control of 3D-fluoroscopy. All patients were supplied with an
      orthesis after the operation which allowed weight bearing of 10 kg for 12 weeks
      for the patients operated between October 2002 and October 2004 (Group A).
      Transient local osteoporosis was observed in all X-Rays at follow-up after an
      average of 8,6 months. Therefore we changed our postoperative treatment plan for
      the patients operated between November 2004 and April 2007 (Group B). Weight
      bearing started with 20 KG after 6 weeks, was increased to 40 KG after 8 weeks
      and full weight bearing was allowed after 10 weeks for these patients. In no case
      a secondary dislocation of the fracture was seen. No bone graft was used. At
      follow up the average American Foot and Ankle Society Score (AOFAS) were 81 for
      Group_A, compared to 84 for Group B, treated with earlier weight bearing.
      Autologous bone graft was not necessary even if weight bearing was started after
      a period of six weeks postoperatively. The combination of 3D-fluoroscopy with
      locked internal fixation showed promising results. If the rate of patients
      developing subtalar arthrosis will decrease by this management will have to be
      shown in long term follow up.

PMID- 19750016
TI  - Perturbation of mouse retinal vascular morphogenesis by anthrax lethal toxin.
AB  - Lethal factor, the enzymatic moiety of anthrax lethal toxin (LeTx) is a protease
      that inactivates mitogen activated protein kinase kinases (MEK or MKK). In vitro
      and in vivo studies demonstrate LeTx targets endothelial cells. However, the
      effects of LeTx on endothelial cells are incompletely characterized. To gain
      insight into this process we used a developmental model of vascularization in the
      murine retina. We hypothesized that application of LeTx would disrupt normal
      retinal vascularization, specifically during the angiogenic phase of vascular
      development. By immunoblotting and immunofluorescence microscopy we observed that
      MAPK activation occurs in a spatially and temporally regulated manner during
      retinal vascular development. Intravitreal administration of LeTx caused an early
      delay (4 d post injection) in retinal vascular development that was marked by
      reduced penetration of vessels into distal regions of the retina as well as
      failure of sprouting vessels to form the deep and intermediate plexuses within
      the inner retina. In contrast, later stages (8 d post injection) were
      characterized by the formation of abnormal vascular tufts that co-stained with
      phosphorylated MAPK in the outer retinal region. We also observed a significant
      increase in the levels of secreted VEGF in the vitreous 4 d and 8 d after LeTx
      injection. In contrast, the levels of over 50 cytokines other cytokines,
      including bFGF, EGF, MCP-1, and MMP-9, remained unchanged. Finally, co-injection
      of VEGF-neutralizing antibodies significantly decreased LeTx-induced neovascular
      growth. Our studies not only reveal that MAPK signaling plays a key role in
      retinal angiogenesis but also that perturbation of MAPK signaling by LeTx can
      profoundly alter vascular morphogenesis.

PMID- 19750018
TI  - A new technique for precisely and accurately measuring lumbar spine bone mineral
      density in mice using clinical dual energy X-ray absorptiometry (DXA).
AB  - Dual Energy X-ray Absorptiometry (DXA) is effective in measuring bone mineral
      density (BMD) in mice for early detection of osteoporosis. However, scanners
      designed for use with small animals (i.e. PIXImus) are very expensive. Used human
      DXA machines are cheaper to obtain, but analysis of scans from these instruments
      is operator-dependent. Obtaining reliable data depends on having a single
      operator analyze the scans in a blinded fashion. Scan quality is improved by
      excising the bone prior to scanning, which does not allow serial measurements.
      This study describes a novel method of analyzing lumbar spine BMD in mice using
      whole body DXA. This non-invasive technique has a high degree of precision and
      reproducibility, with good correlation between multiple observers. Inter-observer
      variability (0.063 +/- 0.00317 g/cm(2) [mean +/- SD], 5.05 [% coefficient of
      variation (CV)], repeat scan variability (0.063 +/- 0.00364 g/cm(2) [mean +/-
      SD], 5.94 [%CV]) were very low compared to variability between different animals
      (0.063 +/- 0.00588 g/cm(2) [mean +/- SD], 9.64 [%CV]) and variability seen in
      same animal over time (0.011 +/- 0.00885 g/cm(2) [mean +/- SD], 80.68 [%CV]). The
      measurement error is thus smaller than the biological variation. Accuracy was
      determined by comparing average peak BMD from two scans per mouse in-vivo (0.066
      g/cm(2)) versus excised spine (0.065 g/cm(2)). Furthermore, correlation between
      bone ash weights and whole body lumbar spine BMD measurements (p < 0.0001) was
      highly significant. This technique thus shows a high degree of precision and
      accuracy, even with multiple observers, for measuring BMD in mice using a DXA
      machine designed for clinical use.

PMID- 19750019
TI  - 210Po Log-normal distribution in human urines: survey from central Italy people.
AB  - The death in London of the former secret service agent Alexander Livtinenko on 23
      November 2006 generally attracted the attention of the public to the rather
      unknown radionuclide (210)Po. This paper presents the results of a monitoring
      programme of (210)Po background levels in the urines of noncontaminated people
      living in Central Italy (near the Republic of S. Marino). The relationship
      between age, sex, years of smoking, number of cigarettes per day, and (210)Po
      concentration was also studied. The results indicated that the urinary (210)Po
      concentration follows a surprisingly perfect Log-normal distribution. Log (210)Po
      concentrations were positively correlated to age (p < 0.0001), number of daily
      smoked cigarettes (p = 0.006), and years of smoking (p = 0.021), and associated
      to sex (p = 0.019). Consequently, this study provides upper reference limits for
      each sub-group identified by significantly predictive variables.

PMID- 19750020
TI  - Determination of migration monomer styrene from GPPS (general purpose
      polystyrene) and HIPS (high impact polystyrene) cups to hot drinks.
AB  - In this study, 162 samples were analysed for monomer styrene content with using
      high performance liquid chromatography (HPLC) method in hot tea, milk, cocoa
      milk. The monomer styrene content, expressed in microg/l of drink and the level
      of migration of styrene monomer were varied from 0.61 to 8.15 for hot tea, from
      0.65 to 8.30 for hot milk, from 0.71 to 8.65 for hot cocoa milk in GPPS (general
      purpose polystyrene), from 0.48 to 6.85 for hot tea, from 0.61 to 7.65 for hot
      milk, from 0.72 to 7.78 for hot cocoa milk in HIPS (high performance polystyrene)
      cups in different temperatures and times. The estimated limit of detection of
      (HPLC) method for all samples was 0.001 mg/kg. There is linear regression for
      styrene monomer from 1 to 10 ng/ml. Several samples spiked with a known amount of
      styrene monomer. The results of the recovery in study for styrene monomer were
      determinate to be mean, 96.1 +/- 1.92 to 99.7 +/- 1.15%. The results of this
      study indicate that styrene monomer from polystyrene disposable into hot and fat
      drinks was migrated and this migration was highly dependent on fat content and
      temperature of drinks. The derived concentration of styrene monomer in this study
      was above the EPA (Environmental protection agency) recommended level, especially
      in MCLG (Maximum contaminant level goal) standard. More study is needed to
      further elucidate this finding.

PMID- 19750021
TI  - Developmental toxicity and brain aromatase induction by high genistein
      concentrations in zebrafish embryos.
AB  - Genistein is a phytoestrogen found at a high level in soybeans. In vitro and in
      vivo studies showed that high concentrations of genistein caused toxic effects.
      This study was designed to test the feasibility of zebrafish embryos for
      evaluating developmental toxicity and estrogenic potential of high genistein
      concentrations. The zebrafish embryos at 24 h post-fertilization were exposed to
      genistein (1 x 10(-4) M, 0.5 x 10(-4) M, 0.25 x 10(-4) M) or vehicle (ethanol,
      0.1%) for 60 h. Genistein-treated embryos showed decreased heart rates, retarded
      hatching times, decreased body length, and increased mortality in a dose
      dependent manner. After 0.25 x 10(-4) M genistein treatment, malformations of
      survived embryos such as pericardial edema, yolk sac edema, and spinal kyphosis
      were also observed. TUNEL assay results showed apoptotic DNA fragments in brain.
      This study also confirmed the estrogenic potential of genistein by EGFP
      expression in the brain of the mosaic reporter zebrafish embryos. This study
      first demonstrated that high concentrations of genistein caused a teratogenic
      effect on zebrafish embryos and confirmed the estrogenic potential of genistein
      in mosaic reporter zebrafish embryos.

PMID- 19750022
TI  - Apoptosis induced by acrylamide is suppressed in a 21.5% fat diet through caspase
      3-independent pathway in mice testis.
AB  - This study investigates the simultaneous effect of acrylamide (ACR) and high-fat
      intake on the apoptosis in testis cells, and also the expression and activity of
      caspase-3. Seventy-two male Kunming mice were divided into two blocks and fed
      with a high-fat diet (crude fat 21.5%) or basic diet (crude fat 4.4%),
      respectively; and animals in each diet block were exposed to ACR at the dose of
      20 mg/kgbw x d or 40 mg/kgbw x d as ACR treated groups or the normal saline as
      control. Germ cells prepared from testis were stained with Hoechst dye 33258 and
      paraffin wax sections from testis were suffered to a TUNEL process. Expression of
      caspase-3 on protein level was investigated using an immunohistochemical analysis
      assay. The supernatant of unilateral testes were subjected to a Caspase-3
      activity kit to determine the activity of Caspase-3 in testis. The concentration
      of ACR and glycidamide(GA), epoxide of ACR, in plasma and testis were detected by
      LC-ES/MS/MS analysis. Results based on the morphological changes, percentage of
      apoptotic cells, and integrated optical density (IOD) of positive amethyst
      staining which indicates the apoptotic DNA fragmentation, show that apoptosis was
      induced by acrylamide only; however, acrylamide-induced apoptosis was weakened by
      high-fat-intake. The protein expression and activity of Caspase-3 were not
      induced by ACR or high-fat-intake. Moreover, no significant differences of ACR
      and GA concentration were found between the high-fat and basic diet groups after
      exposure of ACR. Results indicate that high-fat-intake reverses the effects on
      apoptosis induced by ACR; and more possibly, apoptosis is induced by a caspase-3
      independent mechanism.

PMID- 19750023
TI  - Variance estimation in the analysis of microarray data.
AB  - Microarrays are one of the most widely used high throughput technologies. One of
      the main problems in the area is that conventional estimates of the variances
      that are required in the t-statistic and other statistics are unreliable owing to
      the small number of replications. Various methods have been proposed in the
      literature to overcome this lack of degrees of freedom problem. In this context,
      it is commonly observed that the variance increases proportionally with the
      intensity level, which has led many researchers to assume that the variance is a
      function of the mean. Here we concentrate on estimation of the variance as a
      function of an unknown mean in two models: the constant coefficient of variation
      model and the quadratic variance-mean model. Because the means are unknown and
      estimated with few degrees of freedom, naive methods that use the sample mean in
      place of the true mean are generally biased because of the errors-in-variables
      phenomenon. We propose three methods for overcoming this bias. The first two are
      variations on the theme of the so-called heteroscedastic simulation-extrapolation
      estimator, modified to estimate the variance function consistently. The third
      class of estimators is entirely different, being based on semiparametric
      information calculations. Simulations show the power of our methods and their
      lack of bias compared with the naive method that ignores the measurement error.
      The methodology is illustrated by using microarray data from leukaemia patients.

PMID- 19750025
TI  - Watching the Word Go by: On the Time-course of Component Processes in Visual Word
      Recognition.
AB  - We describe a functional architecture for word recognition that focuses on how
      orthographic and phonological information cooperates in initial form-based
      processing of printed word stimuli prior to accessing semantic information.
      Component processes of orthographic processing and orthography-to-phonology
      translation are described, and the behavioral evidence in favor of such
      mechanisms is briefly summarized. Our theoretical framework is then used to
      interpret the results of a large number of recent experiments that have combined
      the masked priming paradigm with electrophysiological recordings. These
      experiments revealed a series of components in the event-related potential (ERP),
      thought to reflect the cascade of underlying processes involved in the transition
      from visual feature extraction to semantic activation. We provide a tentative
      mapping of ERP components onto component processes in the model, hence specifying
      the relative time-course of these processes and their functional significance.

PMID- 19750026
TI  - Can Sir(2) regulate cancer?
AB  - Sirtuin activators, including small molecules such as polyphenols and
      resveratrol, are much desired due to their potential to ameliorate metabolic
      disorder and delay or prevent aging. In contrast, recent studies demonstrate that
      targeted silencing of sirtuin 1 (SIRT1) expression or activity by the deleted in
      breast cancer 1 (DBC1) may be beneficial by promoting p53-induced apoptosis in
      cancer cells, and by sensitizing cancerous cells to radiation therapy. Negative
      SIRT1 regulation also alleviates gene-repression associated with fragile X mental
      retardation syndrome. The targeted activation or inhibition of SIRT1 activity
      therefore emerges as a critical point of regulation in disease pathogenesis.

PMID- 19750027
TI  - Eight tech trends.

PMID- 19750028
TI  - The Truth about Hospital Formularies, Part 2: Survey Shows Many Myths Still Exist
      Years Later.

PMID- 19750029
TI  - Democrats getting their medicare ducks in a row for next year: the quacking is
      getting louder.

PMID- 19750024
TI  - Therapeutic promise and principles: metabotropic glutamate receptors.
AB  - For a number of disease entities, oxidative stress becomes a significant factor
      in the etiology and progression of cell dysfunction and injury. Therapeutic
      strategies that can identify novel signal transduction pathways to ameliorate the
      toxic effects of oxidative stress may lead to new avenues of treatment for a
      spectrum of disorders that include diabetes, Alzheimer's disease, Parkinson's
      disease and immune system dysfunction. In this respect, metabotropic glutamate
      receptors (mGluRs) may offer exciting prospects for several disorders since these
      receptors can limit or prevent apoptotic cell injury as well as impact upon
      cellular development and function. Yet the role of mGluRs is complex in nature
      and may require specific mGluR modulation for a particular disease entity to
      maximize clinical efficacy and limit potential disability. Here we discuss the
      potential clinical translation of mGluRs and highlight the role of novel signal
      transduction pathways in the metabotropic glutamate system that may be vital for
      the clinical utility of mGluRs.

PMID- 19750030
TI  - New drugs drug news.

PMID- 19750031
TI  - Ixabepilone (ixempra), a therapeutic option for locally advanced or metastatic
      breast cancer.
AB  - Ixabepilone (Ixempra) is a member of a new class of cytotoxic agents, the
      epothilones. Epothilones promote tubulin polymerization in vitro and demonstrate
      antitumor activity. This article reviews the preclinical and clinical data that
      have led to the approval of ixabepilone for patients with locally advanced or
      metastatic breast cancer for whom anthracycline and taxane treatments have
      failed.

PMID- 19750032
TI  - Effect of prescription copayments on adherence and treatment failure with oral
      antidiabetic medications.
AB  - BACKGROUND: Previous studies have shown that an increase in cost sharing by
      patients for medications results in reduced medication use. The purpose of our
      study was to determine whether the amount of members' copayments predicted oral
      antidiabetic treatment failure in a managed care population and to analyze the
      relationship between copayments, adherence to therapy, and hemoglobin A(1c)
      levels in patients with type-2 diabetes. METHODS: Health plan members 18 years of
      age or older with type-2 diabetes and who were newly initiated on an oral
      antidiabetic drug (OAD) between January 1, 2002, and January 31, 2006, were
      identified from a managed care population in the U.S. Members were required to
      have continuous eligibility for six or more months before and 12 months after the
      index prescription and were placed into four treatment groups. These patients
      were followed for one year. The time during which they took the index OAD was
      measured until treatment failure (discontinuation of therapy or a switch of the
      index OAD) or censoring of patient data. The medication possession ratio (MPR),
      which was used to calculate adherence, was defined as the number of days that a
      patient had a supply of the index OAD during the year after the index fill,
      divided by 365 days. Copays were identified for every prescription, and the
      amount for each 30 days of treatment was calculated. We used multivariate
      analyses to assess the impact of copays on treatment failure, adjusting for
      differences in member characteristics. RESULTS: Adherence was poor, with an
      overall mean MPR of 0.57, decreasing from 0.58 for the group with a copay of less
      than $10 to 0.52 for patients with a copay of $20 or more. Initial treatment
      failed for 13,091 patients (70%), with approximately 60% of all members
      discontinuing treatment. This discontinuation rate ranged from 55% in the lowest
      copayment group (below $10) to 67% in those with a copay of $30 or more. For
      every $10 increase in copay, OAD treatment was 26% more likely to fail (95%
      confidence interval, 22.3-29.8%; P < 0.0001). CONCLUSION: Higher copays for
      health plan members were a significant predictor of treatment failure. With the
      increased trend toward more cost sharing by members of health plans, ongoing
      evaluation will be necessary to determine the impact on treatment persistence in
      patients with chronic conditions.

PMID- 19750033
TI  - Vaccine declinations present new challenges for public health.

PMID- 19750034
TI  - Universal health care in america:: can the massachusetts model work nationwide?

PMID- 19750036
TI  - Pharmaceutical approval update.

PMID- 19750035
TI  - Digestive disease week and american diabetes association: digestive disease week.

PMID- 19750038
TI  - Misprogram a PCA Pump? It's Easy!

PMID- 19750037
TI  - The jefferson school of health policy and population health.

PMID- 19750039
TI  - Congress agrees on the need for comparativeness research: but funding will be a
      problem.

PMID- 19750040
TI  - New drugs drug news.

PMID- 19750041
TI  - Alvimopan (Entereg), a Peripherally Acting mu-Opioid Receptor Antagonist For
      Postoperative Ileus.

PMID- 19750042
TI  - Medical management of Parkinson's disease.

PMID- 19750043
TI  - Why is health care regulation so complex?

PMID- 19750044
TI  - The Next President's Prescription for Action on Drugs: Obama and McCain Positions
      Similar-with One Major Difference.

PMID- 19750045
TI  - Trends in managing multiple sclerosis.

PMID- 19750046
TI  - PhRMA 2008.

PMID- 19750048
TI  - New Challenges to the FDA's Drug-Labeling Policy: Democrats Are Poised to Pounce.

PMID- 19750047
TI  - A Loud Wake-up Call: Unlabeled Containers Can Lead to Fatalities.

PMID- 19750049
TI  - New drugs drug news.

PMID- 19750050
TI  - Tetrabenazine (Xenazine), An FDA-Approved Treatment Option For Huntington's
      Disease-Related Chorea.

PMID- 19750052
TI  - Chemotherapy Foundation Symposium XXVI: Innovative Cancer Therapy for Tomorrow.

PMID- 19750051
TI  - Interpreting estimates of treatment effects: implications for managed care.

PMID- 19750053
TI  - Fourth annual ophthalmic drug development and delivery summit and third annual
      onmark national payor/provider forum.

PMID- 19750054
TI  - Classification and pharmacological management of obesity.

PMID- 19750055
TI  - Moody's Musings.

PMID- 19750057
TI  - DEA Opens the Door to e-Prescribing Of Controlled Substances: But Pharmacies Balk
      at Security Rules.

PMID- 19750056
TI  - Oops, Sorry, Wrong Patient!: Applying the Joint Commission's "Two-Identifier"
      Rule Goes beyond the Patient's Room.

PMID- 19750058
TI  - New drugs drug news.

PMID- 19750059
TI  - Ceftobiprole, a Broad-Spectrum Cephalosporin With Activity against Methicillin
      Resistant Staphylococcus aureus (MRSA).

PMID- 19750060
TI  - Heparin-induced thrombocytopenia: overview and treatment.

PMID- 19750062
TI  - European society for medical oncology and association for the study of bone and
      mineral research: European society for medical oncology identifying benefited
      subgroups and promising agents.

PMID- 19750063
TI  - Pharmaceutical approval update.

PMID- 19750061
TI  - Medication Utilization Patterns and Hypertension-Related Expenditures among
      Patients Who Were Switched from Fixed-Dose To Free-Combination Antihypertensive
      Therapy.
AB  - Using a retrospective cohort study of medical and pharmacy claims data, we
      evaluated medication compliance, persistence, and hypertension-related
      expenditures among patients who were switched from fixed-dose combination (FDC)
      to free-combination (FC) antihypertensive therapy. An example of a fixed-dose
      combination product for hypertension would be a valsartan/HCT tablet, and a free
      combination product would be a valsartan tablet plus a diuretic tablet.The 7,224
      patients identified from January 2003 to December 2005 were matched, in a 1:1
      ratio, by propensity scores to controls who remained on their FC antihypertensive
      medications. Compliance, defined as a medication-possession ratio, was measured
      over 12 months. Persistence was measured as the percentage of patients who did
      not experience a lapse in therapy of more than 30 days since their last
      prescription refill.The patients continuing with FDC therapy had better
      persistence (42.5% higher; P < 0.002) and compliance (22.1% higher; P < 0.001),
      compared with patients who were switched to FC therapy. The 22.1% higher
      compliance rate for patients continuing the FDC regimen was associated with
      significantly lower expenditures for hypertension-related health care (P < 0.001)
      and an estimated 5% reduction in hypertension-related expenditures.

PMID- 19750064
TI  - The new, improved, online-only primary care companion.

PMID- 19750065
TI  - A computerized decision support system for depression in primary care.
AB  - OBJECTIVE: In 2004, results from The Texas Medication Algorithm Project (TMAP)
      showed better clinical outcomes for patients whose physicians adhered to a paper
      and-pencil algorithm compared to patients who received standard clinical
      treatment for major depressive disorder (MDD). However, implementation of and
      fidelity to the treatment algorithm among various providers was observed to be
      inadequate. A computerized decision support system (CDSS) for the implementation
      of the TMAP algorithm for depression has since been developed to improve fidelity
      and adherence to the algorithm. METHOD: This was a 2-group, parallel design,
      clinical trial (one patient group receiving MDD treatment from physicians using
      the CDSS and the other patient group receiving usual care) conducted at 2
      separate primary care clinics in Texas from March 2005 through June 2006. Fifty
      five patients with MDD (DSM-IV criteria) with no significant difference in
      disease characteristics were enrolled, 32 of whom were treated by physicians
      using CDSS and 23 were treated by physicians using usual care. The study's
      objective was to evaluate the feasibility and efficacy of implementing a CDSS to
      assist physicians acutely treating patients with MDD compared to usual care in
      primary care. Primary efficacy outcomes for depression symptom severity were
      based on the 17-item Hamilton Depression Rating Scale (HDRS(17)) evaluated by an
      independent rater. RESULTS: Patients treated by physicians employing CDSS had
      significantly greater symptom reduction, based on the HDRS(17), than patients
      treated with usual care (P < .001). CONCLUSIONS: The CDSS algorithm, utilizing
      measurement-based care, was superior to usual care for patients with MDD in
      primary care settings. Larger randomized controlled trials are needed to confirm
      these findings. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00551083.

PMID- 19750066
TI  - Partial adherence to antipsychotic medication impacts the course of illness in
      patients with schizophrenia: a review.
AB  - OBJECTIVE: Although many clinicians acknowledge the occurrence of adherence
      problems with medication regimens among patients with schizophrenia, the problem
      shows no sign of improving. This may be because, in thinking about the issue,
      clinicians have tended to focus on patients who openly refuse or repeatedly
      discontinue treatment. While this description applies to only a minority of
      patients, in our experience, full adherence is rare; most patients are only
      partially adherent at best. This article examines the issue of adherence behavior
      in schizophrenia, focusing on the impact of partial adherence on treatment
      outcomes, particularly early in the course of illness. We also review potential
      strategies for managing the problem. DATA SOURCES: Original research and review
      articles published in English from 1980 to 2008 were identified using the PubMed
      database, with the search terms schizophrenia or psychosis combined with
      compliance, noncompliance, partial compliance, adherence, nonadherence, or
      partial adherence. STUDY SELECTION: Articles were selected by the authors on the
      basis of the hypotheses and/or data described. DATA SYNTHESIS: Failure to adhere
      to medication as prescribed can have a major impact on the course of illness and
      treatment outcomes in patients with schizophrenia. Even relatively short gaps in
      medication coverage increase the risk of relapse. Problems with adherence are
      common early in the course of illness, when the consequences of relapse can be
      particularly devastating. CONCLUSION: Clinicians in primary care and psychiatric
      settings need to be vigilant for signs of adherence problems among their patients
      and to act when necessary to prevent or alleviate the consequences of inadequate
      medication cover. Relapse prevention strategies, particularly for patients with
      early psychosis, should include ensuring that medication lapses are minimized or
      eliminated.

PMID- 19750067
TI  - Tackling partial response to depression treatment.

PMID- 19750069
TI  - MD psychotherapist.

PMID- 19750068
TI  - Lies in the doctor-patient relationship.

PMID- 19750070
TI  - What time is it?

PMID- 19750071
TI  - Quetiapine-Induced Bradycardia Without QT Interval Prolongation in an Elderly
      Woman.

PMID- 19750072
TI  - Systematic review of lithium augmentation in depression resistant to at least 2
      antidepressants.

PMID- 19750073
TI  - Oxcarbazepine-induced reversible anorgasmia and ejaculatory failure: a case
      report.

PMID- 19750074
TI  - Risperidone-induced priapism: a case report.

PMID- 19750075
TI  - EHP's policy on integrity of published research.

PMID- 19750076
TI  - Notes from the editor. Commentaries in EHP.

PMID- 19750077
TI  - Do GST polymorphisms modulate the frequency of chromosomal aberrations in healthy
      subjects?

PMID- 19750079
TI  - Green chemistry: terminology and principles.

PMID- 19750081
TI  - Molybdenum exposure and semen quality: how robust is the evidence of an effect?

PMID- 19750083
TI  - Surveillance and monitoring. Toxics report improves, but data still limited.

PMID- 19750084
TI  - Infectious disease. Digging into seaside microbial exposures.

PMID- 19750086
TI  - Children's health. Sex-specific cognitive effects of lead.

PMID- 19750087
TI  - Swine CAFOs & novel H1N1 flu: separating facts from fears.

PMID- 19750088
TI  - The new USDA: cultivating change.

PMID- 19750089
TI  - New face of a well-known hazard: arsenic alters H1N1 response in mice.

PMID- 19750090
TI  - Polycarbonate plastics and human BPA exposure: urinary levels rise with use of
      drinking bottles.

PMID- 19750091
TI  - Dangerous delicacy: contaminated sea turtle eggs pose a potential health threat.

PMID- 19750092
TI  - A complex relationship: psychosocial stress, pollution, and health.

PMID- 19750093
TI  - The precautionary principle in the context of mobile phone and base station
      radiofrequency exposures.
AB  - BACKGROUND: No health hazard has been established from exposure to radiofrequency
      fields up to the levels recommended by the International Commission on Non
      Ionizing Radiation Protection. However, in response to public concern and the
      perceived level of scientific uncertainty, there are continuing calls for the
      application of the precautionary principle to radiofrequency exposures from
      mobile phones and base stations. OBJECTIVE: We examined the international
      evolution of calls for precautionary measures in relation to mobile phones and
      base stations, with particular focus on Australia and the United Kingdom.
      RESULTS: The precautionary principle is difficult to define, and there is no
      widespread agreement as to how it should be implemented. However, there is a
      strong argument that precautionary measures should not be implemented in the
      absence of reliable scientific data and logical reasoning pointing to a possible
      health hazard. There is also experimental evidence that precautionary advice may
      increase public concern. CONCLUSION: We argue that conservative exposure
      standards, technical features that minimize unnecessary exposures, ongoing
      research, regular review of standards, and availability of consumer information
      make mobile communications inherently precautionary. Commonsense measures can be
      adopted by individuals, governments, and industry to address public concern while
      ensuring that mobile networks are developed for the benefit of society.

PMID- 19750094
TI  - Ad hoc and fast forward: the science of hormesis growth and development.
AB  - BACKGROUND: Hormesis is a binary response phenomenon with low-dose stimulation
      (or inhibition) of effects by substances producing opposite high-dose responses.
      Hormesis, after decades of obscurity, has undergone a renaissance in recent
      years, with rapid growth benefiting greatly from the systematized efforts of such
      proponents as the hormesis group at the University of Massachusetts-Amherst led
      by Edward J. Calabrese. OBJECTIVE: In this commentary I analyze chemical hormesis
      methodology with reference to ad hoc scientific approaches for defining and
      characterizing hormesis. DISCUSSIONS: Proponents of hormesis have attempted a
      scientific characterization of hormesis through a battery of ad hoc methodologies
      using unvalidated criteria and other mechanisms for persistent database searches
      rather than through de novo hypothesis testing specific for hormesis. Here I
      discuss various scientific problems with this search-over-experiment approach, as
      well as other aspects of attempts at defining and characterizing the field.
      CONCLUSIONS: Wide acceptance of hormesis by the broad scientific community and
      adoption of hormesis by public agencies for inclusion in health and regulatory
      policies have not occurred. Reasons may include the singular nature of hormesis
      research and directions followed in hormesis methodologies.

PMID- 19750095
TI  - Hormesis: a conversation with a critic.
AB  - OBJECTIVE: In this commentary I respond to points raised in the commentary by
      Mushak [Ad hoc and fast forward: the science and control of hormesis growth and
      development. Environ Health Perspect 117:1333-1338 (2009)], which principally
      concerns studies by me and my colleagues concerning the frequency of hormesis in
      toxicology. DISCUSSION: In this commentary I demonstrate that Mushak's analysis
      contains critical statistical errors and misunderstandings of statistical
      concepts that invalidate its conclusions concerning the frequency of hormesis in
      the toxicologic literature. CONCLUSIONS: In his commentary Mushak offers no
      significant new conceptual insights, and his key technical criticisms of hormesis
      frequency findings are unfounded.

PMID- 19750096
TI  - Endotoxin and cancer.
AB  - OBJECTIVE: Exposure to endotoxin, a component of gram-negative bacterial cell
      walls, is widespread in many industrial settings and in the ambient environment.
      Heavy-exposure environments include livestock farms, cotton textile facilities,
      and saw mills. Concentrations are highly variable in non-occupational indoor and
      outdoor environments. Endotoxin is a potent inflammagen with recognized health
      effects, including fever, shaking chills, septic shock, toxic pneumonitis, and
      respiratory symptoms. Somewhat paradoxically, given the putative role of
      inflammation in carcinogenesis, various lines of evidence suggest that endotoxin
      may prevent cancer initiation or limit tumor growth. The hypothesis that
      components of bacteria may retard cancer progression dates back to William B.
      Coley's therapeutic experiments ("bacterial vaccine") in the 1890s. DATA SOURCES:
      In this article, we review epidemiologic, clinical trial, and experimental
      studies pertinent to the hypothesis that endotoxin prevents cancer. Since the
      1970s, epidemiologic studies of cotton textile and other endotoxin-exposed
      occupational groups have consistently demonstrated reduced lung cancer risks.
      Experimental animal toxicology research and some limited therapeutic trials in
      cancer patients offer additional support for an anticarcinogenic potential. The
      underlying biological mechanisms of anticarcinogenesis are not entirely
      understood but are thought to involve the recruitment and activation of immune
      cells and proinflammatory mediators (e.g., tumor necrosis factor alpha and
      interleukin-1 and -6). CONCLUSIONS: In view of the current state of knowledge, it
      would be premature to recommend endotoxin as a cancer-chemopreventive agent.
      Nonetheless, further epidemiologic and experimental investigations that can
      clarify further dose-effect and exposure-timing relations could have substantial
      public health and basic biomedical benefits.

PMID- 19750097
TI  - A framework for examining social stress and susceptibility to air pollution in
      respiratory health.
AB  - OBJECTIVE: There is growing interest in disentangling the health effects of
      spatially clustered social and physical environmental exposures and in exploring
      potential synergies among them, with particular attention directed to the
      combined effects of psychosocial stress and air pollution. Both exposures may be
      elevated in lower-income urban communities, and it has been hypothesized that
      stress, which can influence immune function and susceptibility, may potentiate
      the effects of air pollution in respiratory disease onset and exacerbation. In
      this paper, we attempt to synthesize the relevant research from social and
      environmental epidemiology, toxicology, immunology, and exposure assessment to
      provide a useful framework for environmental health researchers aiming to
      investigate the health effects of environmental pollution in combination with
      social or psychological factors. DATA SYNTHESIS: We review the existing
      epidemiologic and toxicologic evidence on synergistic effects of stress and
      pollution, and then describe the physiologic effects of stress and key issues
      related to measuring and evaluating stress as it relates to physical
      environmental exposures and susceptibility. Finally, we identify some of the
      major methodologic challenges ahead as we work toward disentangling the health
      effects of clustered social and physical exposures and accurately describing the
      interplay among these exposures. CONCLUSIONS: There is still tremendous work to
      be done toward understanding the combined and potentially synergistic health
      effects of stress and pollution. As this research proceeds, we recommend careful
      attention to the relative temporalities of stress and pollution exposures, to
      nonlinearities in their independent and combined effects, to physiologic pathways
      not elucidated by epidemiologic methods, and to the relative spatial
      distributions of social and physical exposures at multiple geographic scales.

PMID- 19750099
TI  - Polycarbonate bottle use and urinary bisphenol A concentrations.
AB  - BACKGROUND: Bisphenol A (BPA) is a high-production-volume chemical commonly used
      in the manufacture of polycarbonate plastic. Low-level concentrations of BPA in
      animals and possibly in humans may cause endocrine disruption. Whether ingestion
      of food or beverages from polycarbonate containers increases BPA concentrations
      in humans has not been studied. OBJECTIVES: We examined the association between
      use of polycarbonate beverage containers and urinary BPA concentrations in
      humans. METHODS: We conducted a nonrandomized intervention of 77 Harvard College
      students to compare urinary BPA concentrations collected after a washout phase of
      1 week to those taken after an intervention week during which most cold beverages
      were consumed from polycarbonate drinking bottles. Paired t-tests were used to
      assess the difference in urinary BPA concentrations before and after
      polycarbonate bottle use. RESULTS: The geometric mean urinary BPA concentration
      at the end of the washout phase was 1.2 microg/g creatinine, increasing to 2.0
      microg/g creatinine after 1 week of polycarbonate bottle use. Urinary BPA
      concentrations increased by 69% after use of polycarbonate bottles (p < 0.0001).
      The association was stronger among participants who reported > or = 90%
      compliance (77% increase; p < 0.0001) than among those reporting < 90% compliance
      (55% increase; p = 0.03), but this difference was not statistically significant
      (p = 0.54). CONCLUSIONS: One week of polycarbonate bottle use increased urinary
      BPA concentrations by two-thirds. Regular consumption of cold beverages from
      polycarbonate bottles is associated with a substantial increase in urinary BPA
      concentrations irrespective of exposure to BPA from other sources.

PMID- 19750098
TI  - The Pine River statement: human health consequences of DDT use.
AB  - OBJECTIVES: Dichlorodiphenyltrichloroethane (DDT) was used worldwide until the
      1970s, when concerns about its toxic effects, its environmental persistence, and
      its concentration in the food supply led to use restrictions and prohibitions. In
      2001, more than 100 countries signed the Stockholm Convention on Persistent
      Organic Pollutants (POPs), committing to eliminate the use of 12 POPs of greatest
      concern. However, DDT use was allowed for disease vector control. In 2006, the
      World Health Organization and the U.S. Agency for International Development
      endorsed indoor DDT spraying to control malaria. To better inform current policy,
      we reviewed epidemiologic studies published from 2003 to 2008 that investigated
      the human health consequences of DDT and/or DDE
      (dichlorodiphenyldichloroethylene) exposure. DATA SOURCES AND EXTRACTION: We
      conducted a PubMed search in October 2008 and retrieved 494 studies. DATA
      SYNTHESIS: Use restrictions have been successful in lowering human exposure to
      DDT, but blood concentrations of DDT and DDE are high in countries where DDT is
      currently being used or was more recently restricted. The recent literature shows
      a growing body of evidence that exposure to DDT and its breakdown product DDE may
      be associated with adverse health outcomes such as breast cancer, diabetes,
      decreased semen quality, spontaneous abortion, and impaired neurodevelopment in
      children. CONCLUSIONS: Although we provide evidence to suggest that DDT and DDE
      may pose a risk to human health, we also highlight the lack of knowledge about
      human exposure and health effects in communities where DDT is currently being
      sprayed for malaria control. We recommend research to address this gap and to
      develop safe and effective alternatives to DDT.

PMID- 19750100
TI  - Modification of the interleukin-6 response to air pollution by interleukin-6 and
      fibrinogen polymorphisms.
AB  - BACKGROUND: Evidence suggests that cardiovascular effects of air pollution are
      mediated by inflammation and that air pollution can induce genetic expression of
      the interleukin-6 gene (IL6). OBJECTIVES: We investigated whether IL6 and
      fibrinogen gene variants can affect plasma IL-6 responses to air pollution in
      patients with cardiovascular disease. METHODS: We repeatedly determined plasma IL
      6 in 955 myocardial infarction survivors from six European cities (n = 5,539). We
      conducted city-specific analyses using additive mixed models adjusting for
      patient characteristics, time trend, and weather to assess the impact of air
      pollutants on plasma IL-6. We pooled city-specific estimates using meta-analysis
      methodology. We selected three IL6 single-nucleotide polymorphisms (SNPs) and one
      SNP each from the fibrinogen alpha-chain gene (FGA) and beta-chain gene (FGB) for
      gene-environment analyses. RESULTS: We found the most consistent modifications
      for variants in IL6 rs2069832 and FBG rs1800790 after exposure to carbon monoxide
      (CO; 24-hr average; p-values for interaction, 0.034 and 0.019, respectively).
      Nitrogen dioxide effects were consistently modified, but p-values for interaction
      were larger (0.09 and 0.19, respectively). The strongest effects were seen 6-11
      hr after exposure, when, for example, the overall effect of a 2.2% increase in IL
      6 per 0.64 mg/m(3) CO was modified to a 10% (95% confidence interval, 4.6-16%)
      increase in IL-6 (p-value for interaction = 0.002) for minor homozygotes of FGB
      rs1800790. CONCLUSIONS: The effect of gaseous traffic-related air pollution on
      inflammation may be stronger in genetic subpopulations with ischemic heart
      disease. This information could offer an opportunity to identify postinfarction
      patients who would benefit more than others from a cleaner environment and
      antiinflammatory treatment.

PMID- 19750101
TI  - Thyroid function and plasma concentrations of polyhalogenated compounds in Inuit
      adults.
AB  - BACKGROUND: Several ubiquitous polyhalogenated compounds (PHCs) have been shown
      to alter thyroid function in animal and in vitro studies. So far, epidemiologic
      studies have focused on the potential effect of a small number of them, namely,
      polychlorinated biphenyls (PCBs) and some organochlorines (OCs), without paying
      attention to other important PHCs. OBJECTIVES: We investigated the relationship
      between exposure to several PHCs and thyroid hormone homeostasis in Inuit adults
      from Nunavik. METHODS: We measured thyroid parameters [thyroid-stimulating
      hormone (TSH), free thyroxine (fT(4)), total triiodothyronine (tT(3)), and
      thyroxine-binding globulin (TBG)] and concentrations of 41 contaminants,
      including PCBs and their metabolites, organochlorine pesticides (OCPs),
      polybrominated diphenyl ethers (PBDEs), perfluorooctanesulfonate (PFOS), and a
      measure of dioxin-like compounds, detected in plasma samples from Inuit adults (n
      = 623). RESULTS: We found negative associations between tT(3) concentrations and
      levels of 14 PCBs, 7 hydroxylated PCBs (HO-PCBs), all methylsulfonyl metabolites
      of PCBs (MeSO(2)-PCBs), and 2 OCPs. Moreover, we found negative associations
      between fT(4) levels and hexachlorobenzene concentrations. TBG concentrations
      were inversely related to 8 PCBs, 5 HO-PCBs, and 3 OCPs. Exposure to BDE-47 was
      positively related to tT (3), whereas PFOS concentrations were negatively
      associated with TSH, tT(3,) and TBG and positively with fT(4) concentrations.
      CONCLUSION: Exposure to several PHCs was associated with modifications of the
      thyroid parameters in adult Inuit, mainly by reducing tT(3) and TBG circulating
      concentrations. The effects of PFOS and BDE-47 on thyroid homeostasis require
      further investigation because other human populations display similar or higher
      concentrations of these chemicals.

PMID- 19750102
TI  - Workplace exposures and the risk of amyotrophic lateral sclerosis.
AB  - BACKGROUND: Occupation has been suggested to play a role in amyotrophic lateral
      sclerosis (ALS) etiology, but detailed information on the importance of specific
      workplace exposures is lacking. OBJECTIVES: Our aim was to assess the
      relationship between workplace exposures and the risk of ALS and to evaluate
      potential interactions between these exposures and smoking. METHODS: We conducted
      a case-control study in New England between 1993 and 1996, comprising 109 cases
      and 253 controls who completed a structured interview covering occupations and
      workplace exposures. Unconditional logistic regression models were used to
      estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for ALS.
      Analyses were conducted among the entire study population and after
      stratification by smoking. RESULTS: We observed a higher risk of ALS for
      construction workers excluding supervisors (OR = 2.9; 95% CI, 1.2-7.2) and
      precision metal workers (OR = 3.5; 95% CI, 1.2-10.5). Self-reported exposures to
      paint strippers; cutting, cooling, or lubricating oils; antifreeze or coolants;
      mineral or white spirits; and dry cleaning agents each appeared to be associated
      with a 60-90% higher risk. Specific chemicals related to a > 50% increase in risk
      of ALS included aliphatic chlorinated hydrocarbons, glycols, glycol ethers, and
      hexane. Relative risks associated with these workplace exposures and chemicals
      were greater among nonsmokers and persisted in mutually adjusted models.
      CONCLUSIONS: Our data suggest that certain occupations and workplace exposures
      may be associated with increased risk of ALS. These results need to be confirmed
      in independent populations.

PMID- 19750103
TI  - Pesticide exposure and hypertensive disorders during pregnancy.
AB  - BACKGROUND: Hypertensive disorders of pregnancy, including pregnancy-induced
      hypertension (PIH) and preeclampsia (PE), complicate 2-8% of pregnancies. Few
      studies have examined environmental risk factors in relation to these conditions.
      OBJECTIVES: Our goal was to examine whether pesticide exposure during pregnancy
      was associated with hypertensive disorders of pregnancy. METHODS: We analyzed
      self-reported data from 11,274 wives of farmers enrolled in the Agricultural
      Health Study (AHS) between 1993 and 1997. Using logistic regression models, we
      estimated the adjusted odds ratios (AORs) for PIH and PE associated with
      pesticide-related activities during the first trimester of pregnancy. RESULTS:
      First-trimester residential and agricultural activities with potential exposure
      to pesticides were associated with both PIH [residential AOR = 1.27; 95%
      confidence interval (CI), 1.02-1.60; agricultural AOR = 1.60; 95% CI, 1.05-2.45]
      and PE (residential AOR = 1.32; 95% CI, 1.02-1.70; agricultural AOR = 2.07; 95%
      CI, 1.34-3.21). CONCLUSIONS: Exposure to pesticides during pregnancy may increase
      the risk of hypertensive disorders of pregnancy. Laboratory research may provide
      insights into relationships between pesticide exposure and hypertensive diseases
      of pregnancy.

PMID- 19750104
TI  - Chemical contamination of green turtle (Chelonia mydas) eggs in peninsular
      Malaysia: implications for conservation and public health.
AB  - BACKGROUND: Persistent organic pollutants (POPs)-such as organochlorine
      pesticides (OCPs), polychlorinated biphenyls (PCBs), and polybrominated diphenyl
      ethers (PBDEs)-and heavy metals have been reported in sea turtles at various
      stages of their life cycle. These chemicals can disrupt development and function
      of wildlife. Furthermore, in areas such as Peninsular Malaysia, where the human
      consumption of sea turtle eggs is prevalent, egg contamination may also have
      public health implications. OBJECTIVE: In the present study we investigated
      conservation and human health risks associated with the chemical contamination of
      green turtle (Chelonia mydas) eggs in Peninsular Malaysia. METHODS: Fifty-five C.
      mydas eggs were collected from markets in Peninsular Malaysia and analyzed for
      POPs and heavy metals. We conducted screening risk assessments (SRAs) and
      calculated the percent of acceptable daily intake (ADI) for POPs and metals to
      assess conservation and human health risks associated with egg contamination.
      RESULTS: C. mydas eggs were available in 9 of the 33 markets visited. These eggs
      came from seven nesting areas from as far away as Borneo Malaysia. SRAs indicated
      a significant risk to embryonic development associated with the observed arsenic
      concentrations. Furthermore, the concentrations of coplanar PCBs represented 3
      300 times the ADI values set by the World Health Organization. CONCLUSIONS: The
      concentrations of POPs and heavy metals reported in C. mydas eggs from markets in
      Peninsular Malaysia pose considerable risks to sea turtle conservation and human
      health.

PMID- 19750105
TI  - Serum cholinesterase inhibition in relation to paraoxonase-1 (PON1) status among
      organophosphate-exposed agricultural pesticide handlers.
AB  - BACKGROUND: Animal studies have demonstrated that low paraoxonase-1 (PON1) status
      (i.e., low catalytic efficiency and/or low plasma PON1 activity) is associated
      with neurotoxic effects after exposure to several organophosphate (OP)
      insecticides. However, few human studies have investigated associations between
      PON1 status and intermediate end points, such as serum cholinesterase
      [butyrylcholinesterase (BuChE)] inhibition, among OP-exposed individuals.
      OBJECTIVES: We evaluated the relation between plasma PON1 status and BuChE
      inhibition among OP-exposed agricultural pesticide handlers. METHODS:
      Agricultural pesticide handlers in Washington State were recruited during the
      2006 and 2007 spray seasons when they were seen for follow-up ChE testing by
      collaborating medical providers as part of a statewide monitoring program. Blood
      samples were collected from 163 participants and tested for PON1 status based on
      plasma PON1 activity [arylesterase (AREase)] and PON1 Q192R genotype. We
      evaluated percent change in BuChE activity from baseline level in relation to
      PON1 status. RESULTS: We observed significantly greater BuChE inhibition among QQ
      homozygotes relative to RR homozygotes (p = 0.036). Lower levels of plasma PON1
      activity were significantly associated with greater BuChE inhibition (p = 0.004).
      These associations remained after adjustment for year, days since baseline test,
      age, and OP exposure in the last 30 days. CONCLUSIONS: We found that both low
      PON1 catalytic efficiency (i.e., the Q192 alloform) and low plasma PON1 activity
      were associated with BuChE inhibition among OP-exposed agricultural pesticide
      handlers. Corroborative findings from future studies with prospective collection
      of blood samples for PON1 testing, more sensitive markers of OP-related effects,
      and larger sample sizes are needed.

PMID- 19750106
TI  - Serum selenium concentrations and diabetes in U.S. adults: National Health and
      Nutrition Examination Survey (NHANES) 2003-2004.
AB  - BACKGROUND: Increasing evidence suggests that high selenium levels are associated
      with diabetes and other cardiometabolic risk factors. OBJECTIVES: We evaluated
      the association of serum selenium concentrations with fasting plasma glucose,
      glycosylated hemoglobin levels, and diabetes in the most recently available
      representative sample of the U.S. population. METHODS: We used a cross-sectional
      analysis of 917 adults > or = 40 years of age who had a fasting morning blood
      sample in the National Health and Nutrition Examination Survey 2003-2004. We
      evaluated the association of serum selenium, measured by inductively coupled
      plasma-dynamic reaction cell-mass spectrometry, and diabetes, defined as a self
      report of current use of hypoglycemic agents or insulin or as fasting plasma
      glucose > or = 126 mg/dL. RESULTS: Mean serum selenium was 137.1 microg/L. The
      multivariable adjusted odds ratio [95% confidence interval (CI)] for diabetes
      comparing the highest quartile of serum selenium (> or = 147 microg/L) with the
      lowest (< 124 microg/L) was 7.64 (3.34-17.46). The corresponding average
      differences (95% CI) in fasting plasma glucose and glycosylated hemoglobin were
      9.5 mg/dL (3.4-15.6 mg/dL) and 0.30% (0.14-0.46%), respectively. In spline
      regression models, the prevalence of diabetes as well as glucose and glycosylated
      hemoglobin levels increased with increasing selenium concentrations up to 160
      microg/L. CONCLUSIONS: In U.S. adults, high serum selenium concentrations were
      associated with higher prevalence of diabetes and higher fasting plasma glucose
      and glycosylated hemoglobin levels. Given high selenium intake in the U.S.
      population, further research is needed to determine the role of excess selenium
      levels in the development or the progression of diabetes.

PMID- 19750107
TI  - Dietary fat alters body composition, mammary development, and cytochrome p450
      induction after maternal TCDD exposure in DBA/2J mice with low-responsive aryl
      hydrocarbon receptors.
AB  - BACKGROUND: Increased fat intake is associated with obesity and may make obese
      individuals uniquely susceptible to the effects of lipophilic aryl hydrocarbon
      receptor (AHR) ligands. OBJECTIVES: We investigated the consequences of high-fat
      diet (HFD) and AHR ligands on body composition, mammary development, and hepatic
      P450 expression. METHODS: Pregnant C57BL/6J (B6) and DBA/2J (D2) dams,
      respectively expressing high- or low-responsive AHR, were dosed at mid-gestation
      with TCDD. At parturition, mice were placed on an HFD or a low-fat diet (LFD).
      Body fat of progeny was measured before dosing with 7,12
      dimethylbenz[a]anthracene (DMBA). Fasting blood glucose was measured, and liver
      and mammary glands were analyzed. RESULTS: Maternal TCDD exposure resulted in
      reduced litter size in D2 mice and, on HFD, reduced postpartum survival in B6
      mice. In D2 mice, HFD increased body mass and fat in off-spring, induced
      precocious mammary gland development, and increased AHR expression compared with
      mice given an LFD. Maternal TCDD exposure increased hepatic Cyp1a1 and Cyp1b1
      expression in offspring on both diets, but DMBA depressed Cyp1b1 expression only
      in mice fed an HFD. In D2 progeny, TCDD exposure decreased mammary terminal end
      bud size, and DMBA exposure decreased the number of terminal end buds. Only in D2
      progeny fed HFD did perinatal TCDD increase blood glucose and the size of mammary
      fat pads, while decreasing both branch elongation and the number of terminal end
      buds. CONCLUSIONS: We conclude that despite having a low-responsive AHR, D2
      progeny fed a diet similar to that consumed by most people are susceptible to
      TCDD and DMBA exposure effects blood glucose levels, mammary differentiation, and
      hepatic Cyp1 expression.

PMID- 19750108
TI  - Decreased PM10 exposure attenuates age-related lung function decline: genetic
      variants in p53, p21, and CCND1 modify this effect.
AB  - BACKGROUND: Decreasing exposure to airborne particulates was previously
      associated with reduced age-related decline in lung function. However, whether
      the benefit from improved air quality depends on genetic background is not known.
      Recent evidence points to the involvement of the genes p53 and p21 and of the
      cell cycle control gene cyclin D1 (CCND1) in the response of bronchial cells to
      air pollution. OBJECTIVE: We determined in 4,326 participants of the Swiss Cohort
      Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA) whether
      four single-nucleotide polymorphisms in three genes [CCND1 (rs9344 [P242P],
      rs667515), p53 (rs1042522 [R72P]), and p21 (rs1801270 [S31R])] modified the
      previously observed attenuation of the decline in the forced expiratory flow
      between 25% and 75% of the forced vital capacity (FEF(25-75)) associated with
      improved air quality. METHODS: Subjects of the prospective population-based
      SAPALDIA cohort were assessed in 1991 and 2002 by spirometry, questionnaires, and
      biological sample collection for genotyping. We assigned spatially resolved
      concentrations of particulate matter with aerodynamic diameter < or = 10 microm
      (PM(10)) to each participant's residential history 12 months before the baseline
      and follow-up assessments. RESULTS: The effect of diminishing PM(10) exposure on
      FEF(25-75) decline appeared to be modified by p53 R72P, CCND1 P242P, and CCND1
      rs667515. For example, a 10-microg/m(3) decline in average PM(10) exposure over
      an 11-year period attenuated the average annual decline in FEF(25-75) by 21.33
      mL/year (95% confidence interval, 10.57-32.08) among participants homozygous for
      the CCND1 (P242P) GG genotype, by 13.72 mL/year (5.38-22.06) among GA genotypes,
      and by 6.00 mL/year (-4.54 to 16.54) among AA genotypes. CONCLUSIONS: Our results
      suggest that cell cycle control genes may modify the degree to which improved air
      quality may benefit respiratory function in adults.

PMID- 19750109
TI  - Urine arsenic concentrations and species excretion patterns in American Indian
      communities over a 10-year period: the Strong Heart Study.
AB  - BACKGROUND: Arsenic exposure in drinking water disproportionately affects small
      communities in some U.S. regions, including American Indian communities. In U.S.
      adults with no seafood intake, median total urine arsenic is 3.4 microg/L.
      OBJECTIVE: We evaluated arsenic exposure and excretion patterns using urine
      samples collected over 10 years in a random sample of American Indians from
      Arizona, Oklahoma, and North and South Dakota who participated in a cohort study
      from 1989 to 1999. METHODS: We measured total urine arsenic and arsenic species
      [inorganic arsenic (arsenite and arsenate), methylarsonate (MA), dimethylarsinate
      (DMA), and arsenobetaine] concentrations in 60 participants (three urine samples
      each, for a total of 180 urine samples) using inductively coupled plasma/mass
      spectrometry (ICPMS) and high-performance liquid chromatography/ICPMS,
      respectively. RESULTS: Median (10th, 90th percentiles) urine concentration for
      the sum of inorganic arsenic, MA, and DMA at baseline was 7.2 (3.1, 16.9)
      microg/g creatinine; the median was higher in Arizona (12.5 microg/g),
      intermediate in the Dakotas (9.1 microg/g), and lower in Oklahoma (4.4 microg/g).
      The mean percentage distribution of arsenic species over the sum of inorganic and
      methylated species was 10.6% for inorganic arsenic, 18.4% for MA, and 70.9% for
      DMA. The intraclass correlation coefficient for three repeated arsenic
      measurements over a 10-year period was 0.80 for the sum of inorganic and
      methylated species and 0.64, 0.80, and 0.77 for percent inorganic arsenic,
      percent MA, and percent DMA, respectively. CONCLUSIONS: This study found low to
      moderate inorganic arsenic exposure and confirmed long-term constancy in arsenic
      exposure and urine excretion patterns in American Indians from three U.S. regions
      over a 10-year period. Our findings support the feasibility of analyzing arsenic
      species in large population-based studies with stored urine samples.

PMID- 19750110
TI  - Prenatal and early, but not late, postnatal exposure of mice to sidestream
      tobacco smoke increases airway hyperresponsiveness later in life.
AB  - BACKGROUND: Cigarette smoke exposure in utero and during early postnatal
      development increases the incidence of asthma and airway hyperresponsiveness
      (AHR) later in life, suggesting that a possible critical period of developmental
      sensitivity exists in the prenatal and early postnatal periods. OBJECTIVE: We
      investigated mechanisms of susceptibility during critical developmental periods
      to sidestream smoke (SS) exposure and evaluated the possible effects of SS on
      neural responses. METHODS: We exposed three different age groups of mice to
      either SS or filtered air (FA) for 10 consecutive days beginning on gestation day
      (GD) 7 by maternal exposure or beginning on postnatal day (PND) 2 or PND21 by
      direct inhalation. Lung function, airway substance P (SP) innervation, and nerve
      growth factor (NGF) levels in broncho alveolar lavage fluid were measured after a
      single SS exposure on PND59. RESULTS: Methacholine (MCh) dose response for lung
      resistance (R(L)) was significantly elevated, and dynamic pulmonary compliance
      (C(dyn)) was significantly decreased, in the GD7 and PND2 SS exposure groups
      compared with the FA groups after SS exposure on PND59. At the same time points,
      the percent area of SP nerve fibers in tracheal smooth muscle and the levels of
      NGF were significantly elevated. MCh dose-response curves for R(L) and C(dyn), SP
      nerve fiber density, and the level of NGF were not significantly changed in the
      PND21 exposure group after SS exposure on PND59. CONCLUSIONS: These results
      suggest that a critical period of susceptibility to SS exposure exists in the
      prenatal and early postnatal period of development in mice that results in
      increased SP innervation, increased NGF levels in the airway, and enhanced MCh
      AHR later in life.

PMID- 19750111
TI  - Low-dose arsenic compromises the immune response to influenza A infection in
      vivo.
AB  - BACKGROUND: Arsenic exposure is a significant worldwide environmental health
      concern. We recently reported that 5-week exposure to environmentally relevant
      levels (10 and 100 ppb) of As in drinking water significantly altered components
      of the innate immune response in mouse lung, which we hypothesize is an important
      contributor to the increased risk of lung disease in exposed human populations.
      OBJECTIVES: We investigated the effects of As exposure on respiratory influenza A
      (H1N1) virus infection, a common and potentially fatal disease. METHODS: In this
      study, we exposed C57BL/6J mice to 100 ppb As in drinking water for 5 weeks,
      followed by intranasal inoculation with a sub lethal dose of influenza
      A/PuertoRico/8/34 (H1N1) virus. Multiple end points were assessed postinfection.
      RESULTS: Arsenic was associated with a number of significant changes in response
      to influenza, including an increase in morbidity and higher pulmonary influenza
      virus titers on day 7 post-infection. We also found many alterations in the
      immune response relative to As-unexposed controls, including a decrease in the
      number of dendritic cells in the mediastinal lymph nodes early in the course of
      infection. CONCLUSIONS: Our data indicate that chronic As exposure significantly
      compromises the immune response to infection. Alterations in response to repeated
      lung infection may also contribute to other chronic illnesses, such as
      bronchiectasis, which is elevated by As exposure in epidemiology studies.

PMID- 19750112
TI  - Central neuroplasticity and decreased heart rate variability after particulate
      matter exposure in mice.
AB  - BACKGROUND: Epidemiologic studies show that exposure to fine particulate matter
      [aerodynamic diameter < or = 2.5 microm (PM(2.5))] increases the total daily
      cardiovascular mortality. Impaired cardiac autonomic function, which manifests as
      reduced heart rate variability (HRV), may be one of the underlying causes.
      However, the cellular mechanism(s) by which PM(2.5) exposure induces decreased
      HRV is not known. OBJECTIVES: We tested the hypothesis that exposure to PM(2.5)
      impairs HRV by decreasing the excitability of the cardiac vagal neurons in the
      nucleus ambiguus. We also determined the effect of iron on PM-exposure-induced
      decrease in HRV. METHODS: We measured 24-hr HRV in time domains from
      electrocardiogram telemetry recordings obtained in conscious, freely moving mice
      after 3 days of exposure to PM(2.5) in the form of soot only or iron-soot. In
      parallel studies, we determined the intrinsic properties of identified cardiac
      vagal neurons, retrogradely labeled with a fluorescent dye applied to the
      sinoatrial node. RESULTS: Soot-only exposure decreased short-term HRV (root mean
      square of successive difference). With the addition of iron, all HRV parameters
      were significantly reduced. In nonexposed mice, vagal blockade significantly
      reduced all HRV parameters, suggesting that HRV is, in part, under vagal
      regulation in mice. Iron-soot exposure had no significant effect on resting
      membrane potential but decreased spiking responses of the identified cardiac
      vagal neurons to depolarizations (p < 0.05). The decreased spiking response was
      accompanied with a higher minimal depolarizing current required to evoke spikes
      and a lower peak discharge frequency. CONCLUSIONS: The data suggest that PM
      induced neuroplasticity of cardiac vagal neurons may be one mechanism
      contributing to the cardiovascular consequences associated with PM(2.5) exposure
      seen in humans.

PMID- 19750113
TI  - Lower serum testosterone associated with elevated polychlorinated biphenyl
      concentrations in Native American men.
AB  - BACKGROUND: Polychlorinated biphenyls (PCBs) and chlorinated pesticides are
      endocrine disruptors, altering both thyroid and estrogen hormonal systems. Less
      is known of action on androgenic systems. OBJECTIVE: We studied the relationship
      between serum concentrations of testosterone in relation to levels of PCBs and
      three chlorinated pesticides in an adult Native American (Mohawk) population.
      METHODS: We collected fasting serum samples from 703 adult Mohawks (257 men and
      436 women) and analyzed samples for 101 PCB congeners, hexachlorobenzene (HCB),
      dichlorodiphenyldichloroethylene (DDE), and mirex, as well as testosterone,
      cholesterol, and triglycerides. The associations between testosterone and
      tertiles of serum organochlorine levels (both wet weight and lipid adjusted) were
      assessed using a logistic regression model while controlling for age, body mass
      index (BMI), and other analytes, with the lowest tertile being considered the
      referent. Males and females were considered separately. RESULTS: Testosterone
      concentrations in males were inversely correlated with total PCB concentration,
      whether using wet-weight or lipid-adjusted values. The odds ratio (OR) of having
      a testosterone concentration above the median was 0.17 [95% confidence interval
      (CI), 0.05-0.69] for total wet-weight PCBs (highest vs. lowest tertile) after
      adjustment for age, BMI, total serum lipids, and three pesticides. The OR for
      lipid-adjusted total PCB concentration was 0.23 (95% CI, 0.06-0.78) after
      adjustment for other analytes. Testosterone levels were significantly and
      inversely related to concentrations of PCBs 74, 99, 153, and 206, but not PCBs
      52, 105, 118, 138, 170, 180, 201, or 203. Testosterone concentrations in females
      are much lower than in males, and not significantly related to serum PCBs. HCB,
      DDE, and mirex were not associated with testosterone concentration in either men
      or women. CONCLUSIONS: Elevation in serum PCB levels is associated with a lower
      concentration of serum testosterone in Native American men.

PMID- 19750114
TI  - Serum polybrominated diphenyl ether (PBDE) levels are higher in children (2-5
      years of age) than in infants and adults.
AB  - BACKGROUND: Polybrominated diphenyl ethers (PBDEs) are used as flame retardants
      in many products and have been detected in human samples worldwide. Limited data
      show that concentrations are elevated in young children. OBJECTIVES: We
      investigated the association between PBDEs and age with an emphasis on young
      children from Australia in 2006-2007. METHODS: We collected human blood serum
      samples (n = 2,420), which we stratified by age and sex and pooled for analysis
      of PBDEs. RESULTS: The sum of BDE-47, -99, -100, and -153 concentrations (
      summation operator(4)PBDE) increased from 0-0.5 years (mean +/- SD, 14 +/- 3.4
      ng/g lipid) to peak at 2.6-3 years (51 +/- 36 ng/g lipid; p < 0.001) and then
      decreased until 31-45 years (9.9 +/- 1.6 ng/g lipid). We observed no further
      significant decrease among ages 31-45, 45-60 (p = 0.964), or > 60 years (p =
      0.894). The mean summation operator(4)PBDE concentration in cord blood (24 +/- 14
      ng/g lipid) did not differ significantly from that in adult serum at ages 15-30
      (p = 0.198) or 31-45 years (p = 0.140). We found no temporal trend when we
      compared the present results with Australian PBDE data from 2002-2005. PBDE
      concentrations were higher in males than in females; however, this difference
      reached statistical significance only for BDE-153 (p = 0.05). CONCLUSIONS: The
      observed peak concentration at 2.6-3 years of age is later than the period when
      breast-feeding is typically ceased. This suggests that in addition to the
      exposure via human milk, young children have higher exposure to these chemicals
      and/or a lower capacity to eliminate them.

PMID- 19750115
TI  - Influence of prenatal lead exposure on genomic methylation of cord blood DNA.
AB  - BACKGROUND: Fetal lead exposure is associated with adverse pregnancy outcomes and
      developmental and cognitive deficits; however, the mechanism(s) by which lead
      induced toxicity occurs remains unknown. Epigenetic fetal programming via DNA
      methylation may provide a pathway by which environmental lead exposure can
      influence disease susceptibility. OBJECTIVE: This study was designed to determine
      whether prenatal lead exposure is associated with alterations in genomic
      methylation of leukocyte DNA levels from umbilical cord samples. METHODS: We
      measured genomic DNA methylation, as assessed by Alu and LINE-1 (long
      interspersed nuclear element-1) methylation via pyrosequencing, on 103 umbilical
      cord blood samples from the biorepository of the Early Life Exposures in Mexico
      to Environmental Toxicants (ELEMENT) study group. Prenatal lead exposure had been
      assessed by measuring maternal bone lead levels at the mid-tibial shaft and the
      patella using a spot-source (109)Cd K-shell X-ray fluorescence instrument.
      RESULTS: We found an inverse dose-response relationship in which quartiles of
      patella lead correlated with cord LINE-1 methylation (p for trend = 0.01) and and
      tibia lead correlated with Alu methylation (p for trend = 0.05). In mixed effects
      regression models, maternal tibia lead was negatively associated with umbilical
      cord genomic DNA methylation of Alu (beta= -0.027; p = 0.01). We found no
      associations between cord blood lead and cord genomic DNA methylation.
      CONCLUSIONS: Prenatal lead exposure is inversely associated with genomic DNA
      methylation in cord blood. These data suggest that the epigenome of the
      developing fetus can be influenced by maternal cumulative lead burden, which may
      influence long-term epigenetic programming and disease susceptibility throughout
      the life course.

PMID- 19750117
TI  - FDA's Janet Woodcock Riding High: CDER Director Wins "Wows" Amid Agency Woes.
AB  - An in-depth interview with the director of the FDA's Center for Drug Evaluation
      and Research reveals a conscientious leader who is receiving high marks for her
      candor about the agency's challenges.

PMID- 19750116
TI  - Maternal pregnancy levels of polychlorinated biphenyls and risk of hypospadias
      and cryptorchidism in male offspring.
AB  - BACKGROUND: The etiologies of the male urogenital anomalies cryptorchidism and
      hypospadias are poorly understood. It has been suggested, however, that in utero
      hormone levels may be related to risk. Endocrine-disrupting chemicals, including
      polychlorinated biphenyl (PCB) compounds, may alter hormone levels and thereby
      affect the fetus. OBJECTIVES: To examine whether in utero PCB exposure is related
      to cryptorchidism and hypospadias, we examined PCB levels among pregnant women
      enrolled in the Collaborative Perinatal Project (CPP). METHODS: The CPP enrolled
      pregnant women at 12 U.S. medical centers between 1959 and 1965. For the present
      research, we analyzed third-trimester serum samples from the mothers of 230 sons
      with cryptorchidism, 201 sons with hypospadias, and 593 sons with neither
      condition. We estimated adjusted odds ratios (ORs) and 95% confidence intervals
      (CIs) using logistic regression and examined the associations of each anomaly
      with individual PCB congener levels, sum of PCBs, and several functional
      groupings of PCBs. RESULTS: In general, the ORs for cryptorchidism or hypospadias
      showed no notable associations with individual PCB congener levels or functional
      groupings of PCBs. However, the ORs and 95% CIs for the sum of PCBs associated
      with hypospadias were as follows: 0-1.9 microg/L, reference group; 2-2.9
      microg/L, OR = 1.57, 95% CI, 1.05-2.34; 3-3.9 microg/L, OR = 1.45, 95% CI, 0.90
      2.34; and > or = 4.0 microg/L, OR = 1.69, 95% CI, 1.06-2.68; p-value for trend =
      0.08. CONCLUSIONS: Given the large number of associations examined, these
      findings do not strongly support the hypothesis that PCBs are associated with
      cryptorchidism or hypospadias. Because population serum PCB levels at the time of
      sample collection were considerably higher than levels at present, it is unlikely
      that current PCB exposure is related to the development of either anomaly.

PMID- 19750118
TI  - American society of clinical oncology.
AB  - The 2008 American Society of Clinical Oncology Meeting, the 44th and the largest
      so far in its history, hosted 34,000 oncologists and industry exhibitors, with
      312 journalists on-site. Among more than 11,000 abstracts presented, key sessions
      touched on the pharmacological treatment of breast cancer, renal cell carcinoma,
      chronic myelogenous leukemia, non-small-cell lung cancer, bone resorption, and
      advanced melanoma.

PMID- 19750120
TI  - The law of unintended consequences: when pain management leads to medication
      errors.
AB  - In 2001, The Joint Commission released new pain guidelines and attempted to
      address the problem of undertreated pain; however, the resulting focus on the
      pain score number has inadvertently led to some serious adverse drug events. In
      addition, the recent dramatic increase in opioid use has resulted in greater
      abuse of these prescribed drugs, often by teenagers.

PMID- 19750119
TI  - The pharmacological management of migraine, part 1: overview and abortive
      therapy.
AB  - Migraine is the most common headache complaint in clinical practice. Part 1 of a
      two-part series presents a summary of treatments used to reduce the severity and
      duration of migraine and its associated symptoms and also discusses the
      comorbidities, clinical presentation, and risk factors associated with this
      affliction.

PMID- 19750122
TI  - Changes in visual function and thickness of macula after photodynamic therapy for
      age-related macular degeneration.
AB  - PURPOSE: To determine the correlation between the changes in the central retinal
      sensitivity and the changes in the foveal thickness (FT) after photodynamic
      therapy (PDT) for age-related macular degeneration (AMD). METHODS: Nineteen eyes
      of 19 patients with choroidal neovasularizations (CNVs) secondary to AMD were
      studied. The pretreatment values of the central retinal sensitivity determined by
      Micro Perimeter 1 (MP1; Nidek Technologies), best-corrected visual acuity (BCVA),
      and optical coherence tomography (OCT)-determined FT were compared to the
      postoperative values at three and six months after PDT. RESULTS: At six months,
      the retinal sensitivity within the central 10 degrees was significantly improved
      (P = 0.02) and the FT was significantly thinner (P = 0.016). The BCVA, however,
      did not change significantly (P = 0.80). The changes in the retinal sensitivities
      were significantly correlated with the changes in the decrease in the FT (r = -
      0.59, P = 0.012 within the central 10 degrees ) at six months after PDT.
      CONCLUSION: Significant improvements in retinal sensitivities within the central
      10 degrees and a decrease in FT were observed even though the BCVA was not
      significantly improved. The measurement of retinal sensitivity by MP1 may be a
      better method to assess central visual function than the conventional visual
      acuity after PDT.

PMID- 19750121
TI  - Canalization of gene expression in the Drosophila blastoderm by gap gene cross
      regulation.
AB  - Developing embryos exhibit a robust capability to reduce phenotypic variations
      that occur naturally or as a result of experimental manipulation. This reduction
      in variation occurs by an epigenetic mechanism called canalization, a phenomenon
      which has resisted understanding because of a lack of necessary molecular data
      and of appropriate gene regulation models. In recent years, quantitative gene
      expression data have become available for the segment determination process in
      the Drosophila blastoderm, revealing a specific instance of canalization. These
      data show that the variation of the zygotic segmentation gene expression patterns
      is markedly reduced compared to earlier levels by the time gastrulation begins,
      and this variation is significantly lower than the variation of the maternal
      protein gradient Bicoid. We used a predictive dynamical model of gene regulation
      to study the effect of Bicoid variation on the downstream gap genes. The model
      correctly predicts the reduced variation of the gap gene expression patterns and
      allows the characterization of the canalizing mechanism. We show that the
      canalization is the result of specific regulatory interactions among the zygotic
      gap genes. We demonstrate the validity of this explanation by showing that
      variation is increased in embryos mutant for two gap genes, Kruppel and knirps,
      disproving competing proposals that canalization is due to an undiscovered
      morphogen, or that it does not take place at all. In an accompanying article in
      PLoS Computational Biology (doi:10.1371/journal.pcbi.1000303), we show that cross
      regulation between the gap genes causes their expression to approach dynamical
      attractors, reducing initial variation and providing a robust output. These
      results demonstrate that the Bicoid gradient is not sufficient to produce gap
      gene borders having the low variance observed, and instead this low variance is
      generated by gap gene cross regulation. More generally, we show that the complex
      multigenic phenomenon of canalization can be understood at a quantitative and
      predictive level by the application of a precise dynamical model.

PMID- 19750123
TI  - Ocular blood flow levels and visual prognosis in a patient with nonischemic type
      central retinal vein occlusion.
AB  - We look at the case of a 39-year-old female patient suffering from a sudden
      decrease in her left visual acuity (0.08). Her macular edema was examined using
      optical coherence tomography, and her optic disc blood flow was examined with
      laser speckle flowgraphy (LSFG). Additionally, the degree of seriousness of the
      central vein occlusion was evaluated through fluorescein angiography (FA). Ocular
      fundus findings revealed central vein occlusion associated with macular edema,
      and FA determined her disease type as a nonischemic-central vein occlusion. Daily
      doses of 100 mg of aspirin were administered orally to the patient. Upon
      administration, her ocular blood flow almost immediately increased. In this
      study, we demonstrate the potential of LSFG as a means to investigate ocular
      blood flow.

PMID- 19750124
TI  - Effects of brinzolamide vs timolol as an adjunctive medication to latanoprost on
      circadian intraocular pressure control in primary open-angle glaucoma Japanese
      patients.
AB  - PURPOSE: To study the effect of the concomitant use of brinzolamide and
      latanoprost on the 24-hour variation in intraocular pressure (IOP) in primary
      open-angle glaucoma (POAG) patients first treated with timolol and latanoprost.
      METHODS: We studied 30 eyes from 30 POAG patients previously treated with
      latanoprost monotherapy. After a washout of four weeks in both eyes, all patients
      were treated with 0.5% timolol and latanoprost. Three months after the initiation
      of treatment with timolol and latanoprost, the 24-hour IOP variation was
      measured. Thereafter, all patients were treated with concomitant 1% brinzolamide
      and latanoprost. Three months after changing the therapeutic regimen, the 24-hour
      IOP variation was measured a second time. Latanoprost was administered once a
      day, and timolol and brinzolamide were twice a day. IOP was measured with a
      noncontact tomometer. RESULTS: On treatment with brinzolamide and latanoprost, a
      significant decrease in IOP compared to timolol and latanoprost was observed at
      all time points except at 3 PM and 6 PM. As a group, the patients had a
      significantly lower diurnal mean IOP and nocturnal mean IOP during treatment with
      brinzolamide and latanoprost than with timolol and latanoprost. CONCLUSIONS:
      Treatment of POAG with a combination of brinzolamide and latanoprost demonstrated
      improved hypotensive effects compared with timolol and latanoprost during a 24
      hour period.

PMID- 19750125
TI  - Human Papillomavirus (HPV) Type Distribution in Females with Abnormal Cervical
      Cytology. A Correlation with Histological Study.
AB  - The aim of this study was to determine human papillomavirus (HPV) types
      distribution in cervical preneoplasic lesions in a Southern Spanish population
      and their relationship between HPV type and grade of histopathological
      abnormality. Finally, 232 cervical samples from 135 women with previous
      cytological abnormalities were included in this study. Colposcopy studies and
      biopsies were performed. Haematoxylin-eosin stained slides were observed and
      detection of HPV DNA in cervical swabs was carried out with use of a polymerase
      chain reaction and microarrays technology. The relationship between the presence
      of HPV infection and diagnostic variables was evaluated. HPV 16 was the most
      common type followed by HPV 58, 51, 33 and 31. However, the two HPV types
      targeted in the prophylactic vaccines such as HPV type 16 and 18 were detected in
      only 37 (21.2%) and 2 (1.1%) cases respectively. Thirty-three (18.9%) of samples
      were infected with multiple types, the majority of them with two types. In
      addition, during the follow-up of patients many changes in type distribution were
      observed. Several studies will be necessary in order to evaluate the HPV type
      distribution for therapeutically and prophylactic purposes such as vaccine
      treatment. Also, because of the differences obtained depending of use of various
      DNA technologies, the performance of some comparative studies of the different
      methods from detection of HPV would be advisable in a high population of patients
      and with the most homogeneous conditions possible.

PMID- 19750126
TI  - Resident-to-Resident Aggression in Long-Term Care Facilities: An Understudied
      Problem.
AB  - Resident-to-resident aggression (RRA) between long-term care residents includes
      negative and aggressive physical, sexual, or verbal interactions that in a
      community setting would likely be construed as unwelcome and have high potential
      to cause physical or psychological distress in the recipient. Although this
      problem potentially has high incidence and prevalence and serious consequences
      for aggressors and victims, it has received little direct attention from
      researchers to date. This article reviews the limited available literature on
      this topic as well as relevant research from related areas including: resident
      violence toward nursing home staff, aggressive behaviors by elderly persons, and
      community elder abuse. We present hypothesized risk factors for aggressor,
      victim, and nursing home environment, including issues surrounding cognitive
      impairment. We discuss methodological challenges to studying RRA and offer
      suggestions for future research. Finally, we describe the importance of designing
      effective interventions, despite the lack currently available, and suggest
      potential areas of future research.

PMID- 19750127
TI  - Notice of retraction.

PMID- 19750128
TI  - Enhancement in Sport, and Enhancement outside Sport.
AB  - Sport is one of the first areas in which enhancement has become commonplace. It
      is also one of the first areas in which the use of enhancement technologies has
      been heavily regulated. Some have thus seen sport as a testing ground for
      arguments about whether to permit enhancement. However, I argue that there are
      fairness-based objections to enhancement in sport that do not apply as strongly
      in some other areas of human activity. Thus, I claim that there will often be a
      stronger case for permitting enhancement outside of sport than for permitting
      enhancement in sport. I end by considering some methodological implications of
      this conclusion.

PMID- 19750129
TI  - Field and Experience Influences on Ethical Decision-Making in the Sciences.
AB  - Differences across fields and experience levels are frequently considered in
      discussions of ethical decision-making and ethical behavior. In the present
      study, doctoral students in the health, biological, and social sciences completed
      measures of ethical decision-making. The effects of field and level of experience
      with respect to ethical decision-making, metacognitive reasoning strategies,
      social-behavioral responses, and exposure to unethical events were examined.
      Social and biological scientists performed better than health scientists with
      respect to ethical decision-making. Furthermore, the ethical decision-making of
      health science students decreased as experience increased. Moreover, these
      effects appeared to be linked to the specific strategies underlying participants'
      ethical decision-making. The implications of these findings for ethical decision
      making are discussed.

PMID- 19750130
TI  - Comparative Ultrastructural Analysis of D1 and D5 Dopamine Receptor Distribution
      in the Substantia Nigra and Globus Pallidus of Monkeys.
AB  - Dopamine acts through the D1-like (D1, D5) and D2-like (D2, D3, D4) receptor
      families. Various studies have shown a preponderance of presynaptic dopamine D1
      receptors on axons and terminals in the internal globus pallidus (GPi) and
      substantia nigra reticulata (SNr), but little is known about D5 receptors
      distribution in these brain regions. In order to further characterize the
      potential targets whereby dopamine could mediate its effects in basal ganglia
      output nuclei, we undertook a comparative electron microscopic analysis of D1 and
      D5 receptors immunoreactivity in the GPi and SNr of rhesus monkeys. At the light
      microscopic level, D1 receptor labeling was confined to small punctate elements,
      while D5 receptor immunoreactivity was predominantly expressed in cellular and
      dendritic processes throughout the SNr and GPi. At the electron microscopic
      level, 90% of D1 receptor labeling was found in unmyelinated axons or putative
      GABAergic terminals in both basal ganglia output nuclei. In contrast, D5 receptor
      labeling showed a different pattern of distribution. Although the majority (65
      75%) of D5 receptor immunoreactivity was also found in unmyelinated axons and
      terminals in GPi and SNr, significant D5 receptor immunolabeling was also located
      in dendritic and glial processes. Immunogold studies showed that about 50% of D1
      receptor immunoreactivity in axons was bound to the plasma membrane providing
      functional sites for D1 receptor-mediated effects on transmitter release in GPi
      and SNr. These findings provide evidence for the existence of extrastriatal pre-
      and post-synaptic targets through which dopamine and drugs acting at D1-like
      receptors may regulate basal ganglia outflow and possibly exert some of their
      anti-parkinsonian effects.

PMID- 19750131
TI  - Parenting practices and adolescent sexual behavior: A longitudinal study.
AB  - The effects of parental attitudes, practices, and television mediation on
      adolescent sexual behaviors were investigated in a study of adolescent sexuality
      and media (N=887). Confirmatory factor analyses supported an eight-factor
      parenting model with television mediation factors as constructs distinct from
      general parenting practices. Logistic regressions indicated that adolescents
      reporting greater parental disapproval and limits on viewing at Wave 1 were less
      likely to initiate oral sex between Waves 1 and 2. Adolescents who reported more
      sexual communication with parents were more likely to initiate oral sex. Results
      for vaginal intercourse were similar to those for oral sex. Co-viewing was a
      significant negative predictor of initiation of sexual behavior. Parental
      attitudes and television mediation can delay potentially risky adolescent sexual
      behaviors.

PMID- 19750132
TI  - Complexities in Identifying and Defining Mathematics Learning Disability in the
      Primary School-Age Years.
AB  - This paper is a descriptive report of findings from a prospective longitudinal
      study of math disability (MD). The study was designed to address the incidence of
      MD during primary school, the utility of different MD definitions, and evidence
      of MD subtypes. The results illustrate the dynamic properties of psychometrically
      derived definitions of MD. Different groups of children meet criteria for MD
      depending on which measure(s) are used for identification. Over time, a given
      individual may not continue to meet MD criteria, even when using the same
      assessments. Thus, the findings lead to cautions regarding the single-tool/ one
      time assessment for a clinical diagnosis of MD. Twenty-two of 209 participants
      demonstrated "persistent MD" (MD-p), or MD for more than one school grade.
      Reading disability was relatively more frequent in this MD-p subgroup than in the
      remaining participants (25 percent vs. 7 percent). Reading-related skills were
      correlated with math achievement, as were select visual spatial skills. There was
      minimal overlap between groups who met either a "poor achievement" criteria or an
      "IQ-achievement discrepancy," and the latter was far less stable a measure over
      time than the former. The results highlight the complexities of defining MD and
      illustrate the need for more research in this area.

PMID- 19750133
TI  - Psychoneuroimmunology: Psychology's Gateway to the Biomedical Future.
AB  - How do stressful events and negative emotions influence the immune system, and
      how big are the effects? This broad question has been intensely interesting to
      psychoneuroimmunology researchers over the last 3 decades. Many promising lines
      of work underscore the reasons why this question is still so important and
      pivotal to understanding and other advances. New multidisciplinary permutations
      provide fresh vistas and emphasize the importance of training psychologists more
      broadly so that they will be central and essential players in the advancement of
      biomedical science. 

PMID- 19750135
TI  - The cognitive phenotype of Turner syndrome: Specific learning disabilities.
AB  - Global descriptors of the cognitive phenotype of Turner syndrome are well
      established and are thus commonly referred to. For example, Turner syndrome is a
      proposed etiology of the nonverbal learning disability - because of reported
      relative strengths in verbal skills, and relatively weaker nonverbal skills -
      particularly in arithmetic, select visuospatial skills, and processing speed.
      This profile is observed throughout and beyond the school age years. Reliance on
      this gross level description of the cognitive profile (e.g., nonverbal learning
      disability) may be helpful as a starting point when determining whether an
      individual with Turner syndrome has educational needs, but it carries limited
      practical significance when determining the specific nature of these needs. The
      limitations stem from the fact that the severity of the cognitive profile is
      highly variable among individuals with Turner syndrome; that the "nonverbal"
      difficulties are specific rather than widespread; and that any individual with
      Turner syndrome may also manifest cognitive characteristics independent of Turner
      syndrome. In view of the increased risk for specific cognitive difficulties, a
      detailed assessment prior to the onset of formal schooling (or at the time of
      diagnosis, when diagnosis occurs after 5 years of age) can play an important role
      in determining school readiness and potential need for educational support among
      individual girls with Turner syndrome.

PMID- 19750134
TI  - Loop diuretics in acute decompensated heart failure: necessary? Evil? A necessary
      evil?

PMID- 19750136
TI  - SIGNS OF EMOTION: WHAT CAN PREVERBAL CHILDREN "SAY" ABOUT INTERNAL STATES?
AB  - Do infants explicitly recognize feelings and emotions in themselves and others?
      What would preverbal children say about internal states if they had the words?
      Investigation of infants' emotional understanding is limited by the challenge of
      understanding infant mental states before the onset of speech. I examined the use
      of symbolic gestures by normally hearing, preverbal children to discover whether
      infants and toddlers represent emotion concepts such as sad and scared, and
      feeling words such as sleepy. Participants were 22 children (5-28 months) in a
      childcare program where caregivers modeled symbolic gestures. Gesture use by
      children and caregivers were videotaped and coded to determine context,
      characteristics, and frequency. Twenty of 22 children used symbolic gestures; of
      these, 6 used emotion gestures, and 5 used feeling gestures. These gestures were
      not imitations of adult gestures, and qualitative data reveal their context and
      significance. Symbolic gestures reveal the sophistication of infants' internal
      worlds and their ability and desire to communicate thoughts and feelings.
      Symbolic gestures are a promising methodology for investigating early explicit
      mental processes. As a therapeutic communication tool, symbolic gestures may help
      children express emotions, participate in conversations about emotion, and
      construct their own understanding of internal states.

PMID- 19750137
TI  - Expression of bacterial genes in transgenic tobacco: methods, applications and
      future prospects.
AB  - Tobacco is the most commonly used plant for expression of transgenes from a
      variety of organisms, because it is easily grown and transformed, it provides
      abundant amounts of fresh tissue and has a well-established cell culture system.
      Many bacterial proteins involved in the synthesis of commercial products are
      currently engineered for production in tobacco. Bacterial enzymes synthesized in
      tobacco can enhance protection against abiotic stresses and diseases, and provide
      a system to test applied strategies such as phytoremediation. Examples of
      bacterial gene expression in tobacco include production of antigen proteins from
      several human bacterial pathogens as vaccines, bacterial proteins for enhancing
      resistance against insects, pathogens and herbicides, and bacterial enzymes for
      the production of polymers, sugars, and bioethanol. Further improvements in the
      expression of recombinant proteins and their recovery from tobacco will enhance
      production and commercial use of these proteins. This review highlights the
      dynamic use of tobacco in bacterial protein production by examining the most
      relevant research in this field.

PMID- 19750138
TI  - Metacognitive Judgments and Control of Study.
AB  - Recent evidence indicates that people's judgments of their own learning are
      causally related to their study behavior and not epiphenomenal. I argue here that
      people use these metacognitions in an effort to selectively study material in
      their own region of proximal learning. First they attempt to eliminate materials
      that are already well learned. Then they progress successively from studying
      easier to more difficult materials. Successful implementation of this
      metacognitively guided strategy enhances learning. The necessary components are,
      first, that the metacognitions be accurate, and second, that the appropriate
      choices are implemented for study. With these parts in place, the individual is
      in position to effectively take control of his or her own learning.

PMID- 19750139
TI  - Labor supply responses to large social transfers: Longitudinal evidence from
      South Africa.
AB  - In many parts of the developing world, rural areas exhibit high rates of
      unemployment and underemployment. Understanding what prevents people from
      migrating to find better jobs is central to the development process. In this
      paper, we examine whether binding credit constraints and childcare constraints
      limit the ability of households to send labor migrants, and whether the arrival
      of a large, stable source of income - here, the South African old-age pension -
      helps households to overcome these constraints. Specifically, we quantify the
      labor supply responses of prime-aged individuals to changes in the presence of
      pensioners, using longitudinal data collected in KwaZulu-Natal. Our ability to
      compare households and individuals before and after pension receipt, and pension
      loss, allows us to control for a host of unobservable household and individual
      characteristics that may determine labor market behavior. We find that large cash
      transfers to elderly South Africans lead to increased employment among prime-aged
      members of their households, a result that is masked in cross-sectional analysis
      by differences between pension and non-pension households. Pension receipt also
      influences where this employment takes place. We find large, significant effects
      on labor migration upon pension arrival. The pension's impact is attributable
      both to the increase in household resources it represents, which can be used to
      stake migrants until they become self-sufficient, and to the presence of
      pensioners who can care for small children, which allows prime-aged adults to
      look for work elsewhere.

PMID- 19750140
TI  - Infrared micro-spectroscopy of human cells: Causes for the spectral variance of
      oral mucosa (buccal) cells.
AB  - We discuss the causes contributing to the variance of the spectra of individual
      human epithelial cells. This aspect has largely been ignored in previous studies,
      but needs to be understood for diagnostic applications of infrared micro
      spectroscopy. We attribute the spectral variance to Mie scattering, and to
      variations of nuclear contributions to the overall spectra caused by different
      nuclear size.

PMID- 19750141
TI  - Blue-Collar Scholars?: Mediators and Moderators of University Attrition in First
      Generation College Students.
AB  - Many college entrants' parents do not have college degrees. These entrants are at
      high risk for attrition, suggesting it is critical to understand mechanisms of
      attrition relative to parental education. Moderators and mediators of the effect
      of parental education on attrition were investigated in 3,290 students over 4
      years. Low parental education was a risk for attrition; importantly, college GPAs
      both moderated and mediated this effect, and ACT scores, scholarships, loans, and
      full-time work mediated this effect. Drug use, psychological distress, and few
      reported academic challenges predicted attrition, independent of parental
      education. These findings might inform interventions to decrease attrition.

PMID- 19750142
TI  - Dysphoria and memory for emotional material: A diffusion-model analysis.
AB  - Depression-related differences in memory for emotional material are well
      established, but recognition memory and lexical decision tasks often fail to
      produce consistent results. The null results from these tasks could be due to
      inadequacies in traditional analyses rather than the absence of effects. In
      particular, analyses of accuracy or mean reaction times rely on only a fraction
      of the behavioural data and are sensitive to individual differences in response
      biases. The diffusion model addresses these limitations by incorporating all of
      the behavioural data and separating out response biases. We applied the diffusion
      model to data from lexical decision and recognition memory tasks and showed
      consistent effects, specifically a positive emotional bias in non-dysphoric
      subjects and even-handedness in dysphoric subjects. This pattern was not apparent
      with comparisons of reaction times or accuracy, consistent with previous null
      findings. These results suggest a relationship between dysphoria and the internal
      representation of emotional information.

PMID- 19750144
TI  - Adolescent Work Experience and Self-efficacy.
AB  - PURPOSE OF THIS PAPER: To assess the relationship between high school work
      experiences and self-efficacy. DESIGN/METHODOLOGY/APPROACH: OLS regressions are
      applied to longitudinal data from the Youth Development Study to examine work
      experiences and self-efficacy. FINDINGS: The analyses indicate that employment
      fosters self-efficacy in multiple realms, Occasional and sporadic workers exhibit
      less self-efficacy than steady workers. Supervisory support may be especially
      important in enhancing adolescents' confidence as they anticipate their future
      family lives, community participation, personal health, and economic
      achievements. RESEARCH LIMITATIONS/IMPLICATIONS: This research includes only a
      small set of the work dimensions that may be important for adolescents.
      Ethnography and in-depth interviews are recommended to further explore the
      subjective and emotional dimensions of youth work experiences. PRACTICAL
      IMPLICATIONS: In developing policies and guidance, educators, parents, and
      employers should be aware that steady employment and supervisory support enhance
      the development of adolescent self-efficacy. ORIGINAL VALUE OF PAPER: This paper
      finds evidence that adolescent work experiences spill over to influence youth's
      developing confidence in the realms of family life, community and personal
      health. It also suggests that sporadic and occasional work patterns can impair
      the development of self-efficacy in adolescence.

PMID- 19750145
TI  - Estimation of Parameters Subject to Order Restrictions on a Circle With
      Application to Estimation of Phase Angles of Cell Cycle Genes.
AB  - Motivated by a problem encountered in the analysis of cell cycle gene expression
      data, this article deals with the estimation of parameters subject to order
      restrictions on a unit circle. A normal eukaryotic cell cycle has four major
      phases during cell division, and a cell cycle gene has its peak expression (phase
      angle) during the phase that may correspond to its biological function. Because
      the phases are ordered along a circle, the phase angles of cell cycle genes are
      ordered unknown parameters on a unit circle. The problem of interest is to
      estimate the phase angles using the information regarding the order among them.
      We address this problem by developing a circular version of the well-known
      isotonic regression for Euclidean data. Because of the underlying geometry, the
      standard pool adjacent violator algorithm (PAVA) cannot be used for deriving the
      circular isotonic regression estimator (CIRE). However, PAVA can be modified to
      obtain a computationally efficient algorithm for deriving the CIRE. We illustrate
      the CIRE by estimating the phase angles of some of well-known cell cycle genes
      using the unrestricted estimators obtained in the literature.

PMID- 19750146
TI  - The wind chilled the spectators, but the wine just chilled: Sense, structure, and
      sentence comprehension.
AB  - Anticipation plays a role in language comprehension. In this article, we explore
      the extent to which verb sense influences expectations about upcoming structure.
      We focus on change of state verbs like shatter, which have different senses that
      are expressed in either transitive or intransitive structures, depending on the
      sense that is used. In two experiments we influence the interpretation of verb
      sense by manipulating the thematic fit of the grammatical subject as cause or
      affected entity for the verb, and test whether readers' expectations for a
      transitive or intransitive structure change as a result. This sense-biasing
      context influenced reading times in the post-verbal regions. Reading times for
      transitive sentences were faster following good-cause than good theme subjects,
      but the opposite pattern was found for intransitive sentences. We conclude that
      readers use sense-contingent subcategorization preferences during on-line
      comprehension.

PMID- 19750147
TI  - Conflict Resolution Between Mexican Origin Adolescent Siblings.
AB  - We investigated correlates of adolescents' sibling conflict resolution strategies
      in 246, two-parent Mexican origin families. Specifically, we examined links
      between siblings' conflict resolution strategies and sibling dyad
      characteristics, siblings' cultural orientations and values, and sibling
      relationship qualities. Data were gathered during home interviews with adolescent
      siblings. Older siblings were more likely to use controlling strategies whereas
      younger siblings were more likely to use nonconfrontation strategies. Cultural
      orientations and familism values were positively linked to siblings' solution
      orientation. Solution orientation strategies were associated with sibling
      intimacy, and control strategies were related to sibling negativity. Discussion
      highlights the importance of considering the cultural context in which sibling
      relationships are embedded.

PMID- 19750143
TI  - Injectable biomaterials for regenerating complex craniofacial tissues.
AB  - Engineering complex tissues requires a precisely formulated combination of cells,
      spatiotemporally released bioactive factors, and a specialized scaffold support
      system. Injectable materials, particularly those delivered in aqueous solution,
      are considered ideal delivery vehicles for cells and bioactive factors and can
      also be delivered through minimally invasive methods and fill complex 3D shapes.
      In this review, we examine injectable materials that form scaffolds or networks
      capable of both replacing tissue function early after delivery and supporting
      tissue regeneration over a time period of weeks to months. The use of these
      materials for tissue engineering within the craniofacial complex is challenging
      but ideal as many highly specialized and functional tissues reside within a small
      volume in the craniofacial structures and the need for minimally invasive
      interventions is desirable due to aesthetic considerations. Current biomaterials
      and strategies used to treat craniofacial defects are examined, followed by a
      review of craniofacial tissue engineering, and finally an examination of current
      technologies used for injectable scaffold development and drug and cell delivery
      using these materials.

PMID- 19750148
TI  - Maximizing Efficiency of Enrollment for School-Based Educational Research.
AB  - In this observational study, influences on research enrollment were examined in
      the context of an educational research study. Recruitment materials were sent to
      parents of kindergartners in one of 23 classes across 7 public schools, as an
      invitation to enroll in a longitudinal study. For the 7 classes from 2 of the
      schools, the school principal prepared a cover letter as an introduction to the
      educational study. Inclusion of this cover letter was associated with a
      significantly swifter pace of recruitment and, to a lesser degree, with an
      increase in the number of children enrolled. However, when potential confounding
      variables were controlled, no significant increase in final enrollment count was
      associated with including the cover letter. Thus, inclusion of a cover letter
      from the school principal did not appear to dramatically increase the number of
      parents who elected to enroll their child in the educational study, and it did
      significantly decrease (by 6 weeks) the number of weeks required to achieve final
      enrollment counts.

PMID- 19750149
TI  - Changing diabetes care: an opportunity for the feds.

PMID- 19750151
TI  - FDA science base badly eroded: but will congress provide urgent new funding?

PMID- 19750150
TI  - Evidence-Based Medicine Doesn't Preclude Common Sense.

PMID- 19750152
TI  - New drugs drug news.

PMID- 19750153
TI  - Doripenem (doribax), a new carbapenem antibacterial agent.

PMID- 19750154
TI  - Failures of medicare part d delivery and recommendations for improvement.

PMID- 19750156
TI  - Pharmaceutical approval update.

PMID- 19750155
TI  - San antonio breast cancer symposium.

PMID- 19750157
TI  - Self-monitoring of blood glucose: a pilot review: impact of computer software
      modifications on compliance.

PMID- 19750159
TI  - Slaves to medicine.

PMID- 19750160
TI  - Morphine and Hydromorphone: An Omnipresent Risk of Mix-ups.

PMID- 19750158
TI  - Pain associated with diabetic peripheral neuropathy: a review of available
      treatments.

PMID- 19750161
TI  - Actor's Overdose an Unfortunate Eye Opener: Prescription Drug Abuse a Bigger
      Problem Than Cocaine.

PMID- 19750162
TI  - Medicare part d: still more failures.

PMID- 19750163
TI  - Committees Should Include Informatics; P&T Should Publish More about It.

PMID- 19750164
TI  - New drugs drug news.

PMID- 19750165
TI  - The selegiline transdermal system (emsam): a therapeutic option for the treatment
      of major depressive disorder.
AB  - Although monoamine oxidase inhibitors (MAOIs) at one time represented the
      mainstay of therapy for major depressive disorder (MDD), the risk of acute
      hypertensive reactions following the ingestion of tyramine-rich foods and the
      consequent need to restrict dietary tyramine represent a barrier to their use. In
      this article, we present an overview of the efficacy and safety of a transdermal
      formulation of the MAOI selegiline for the treatment of MDD. Transdermal delivery
      of selegiline at the effective dose of 6 mg every 24 hours eliminates the need
      for a tyramine-restricted diet. Our emphasis on potential drug-drug interactions
      and contraindications should be useful to prescribers who counsel patients with
      MDD.

PMID- 19750166
TI  - The FDA's New Guidance for Off-Label Promotion Is Only a Start.

PMID- 19750167
TI  - Skin and Skin Structure Infections, And Control of Hemostasis during Surgery.

PMID- 19750168
TI  - Pharmaceutical approval update.

PMID- 19750170
TI  - The language of change at p&t.

PMID- 19750169
TI  - Pharmacological management of sickle cell disease.

PMID- 19750171
TI  - The four-way win.

PMID- 19750173
TI  - Senate may compromise on 'biosimilars': but length of market exclusivity poses a
      stumbling block.

PMID- 19750172
TI  - The Truth about Hospital Formularies, Part 1: We've Come a Long Way-or Have We?

PMID- 19750174
TI  - New drugs drug news.

PMID- 19750175
TI  - Combating Non-nucleoside Reverse Transcriptase Inhibitor Resistance with a Focus
      On Etravirine (Intelence) for HIV-1 Infection.

PMID- 19750176
TI  - Monitoring asthma control using claims data and patient-reported outcomes
      measures.

PMID- 19750177
TI  - Low-dose, off-label drotrecogin alfa (xigris) in severe sepsis.
AB  - OBJECTIVE: In this article, we describe a successful low-dose, off-label usage of
      drotrecogin alfa (Xigris), given at 18 mcg/kg per hour, in a patient with severe
      sepsis who had an Acute Physiology and Chronic Health Evaluation II (APACHE II)
      score of 26 and multiorgan failure. PATIENT: A 64-year-old man was admitted to
      the surgical intensive-care unit of Winthrop University Hospital in Mineola, New
      York. After undergoing small-bowel resection secondary to obstruction, he became
      severely septic. Because of his high risk of death (with an APACHE II score of 26
      and two organ failures), he was initially treated with drotrecogin alfa 24 mcg/kg
      per hour, the dose approved by the U.S. Food and Drug Administration (FDA).
      Within four hours, his activated partial thromboplastin time became significantly
      prolonged from a baseline of 27.8 to 92.9 seconds, and he had coffee-ground
      nasogastric tube output. In light of signs of bleeding, drotrecogin alfa was
      temporarily discontinued. After 26 hours without further evidence of bleeding,
      drotrecogin alfa was administered at a lower dose of 18 mcg/kg per hour. The
      manufacturer's recommendation of 96 hours of infusion therapy was completed with
      the lower dosing. The patient's condition improved significantly, and eventually
      he was discharged home. CONCLUSION: This case report demonstrates an alternative
      use of drotrecogin alfa at a lower dose of 18 mcg/kg per hour in a severely
      septic patient who could not tolerate the FDA-approved dose of 24 mcg/kg per hour
      because of bleeding.

PMID- 19750178
TI  - American society of hypertension: 23rd annual scientific meeting and exposition.

PMID- 19750180
TI  - Adaptive and Quality Quadrilateral/Hexahedral Meshing from Volumetric Data.
AB  - This paper describes an algorithm to extract adaptive and quality
      quadrilateral/hexahedral meshes directly from volumetric data. First, a bottom-up
      surface topology preserving octree-based algorithm is applied to select a
      starting octree level. Then the dual contouring method is used to extract a
      preliminary uniform quad/hex mesh, which is decomposed into finer quads/hexes
      adaptively without introducing any hanging nodes. The positions of all boundary
      vertices are recalculated to approximate the boundary surface more accurately.
      Mesh adaptivity can be controlled by a feature sensitive error function, the
      regions that users are interested in, or finite element calculation results.
      Finally, a relaxation based technique is deployed to improve mesh quality.
      Several demonstration examples are provided from a wide variety of application
      domains. Some extracted meshes have been extensively used in finite element
      simulations.

PMID- 19750179
TI  - The pharmacological management of migraine, part 2: preventative therapy.

PMID- 19750181
TI  - Effects of Family Functioning and Identity Confusion on Substance Use and Sexual
      Behavior in Hispanic Immigrant Early Adolescents.
AB  - The present study examined the relationships of (a) changes in adolescent
      reported family functioning and (b) changes in identity confusion to onset of
      substance use and sexual behavior in a sample of 250 Hispanic adolescents from
      immigrant families. Adolescents were followed for 3 years. Results indicated that
      adolescents whose identity confusion scores increased over time were most likely
      to initiate cigarette use, alcohol use, and sexual behavior during the course of
      the study. Adolescents whose identity confusion scores remained stable over time
      were less likely to initiate, and adolescents whose identity confusion scores
      decreased over time were least likely to initiate. The data were consistent with
      the proposition that initial levels of and changes in family functioning appeared
      to be responsible for these associations. Implications for identity research and
      intervention are discussed.

PMID- 19750182
TI  - Inquiring Informationists: A Qualitative Exploration of Our Role.
AB  - OBJECTIVE: The goal of this study is to explore the impact of an informationist
      program at the National Institutes of Health (NIH) Library and to provide a basis
      for further program assessment. In 2001 the NIH Library began its informationist
      program, where librarians with training in both biomedicine and information
      science work alongside researchers. The goal of the program is to facilitate
      researchers' access to and usage of information resources.  METHODS: The
      researchers used qualitative interviews with key informants to characterize the
      current informationist services of user groups. Subjects were selected to capture
      a variety of activities that would show patterns of how the program assists the
      researchers of various NIH groups. Following the interviews, the authors
      extracted recurring and significant themes from the subjects' comments.  RESULTS:
      Interview subjects provided their views on the informationists' skills, impact,
      and team participation. Research results documented that informationists helped
      find resources, provided instruction, and worked as part of the research team.
      The NIH groups currently using this service value their informationists'
      knowledge of library resources and their ability to access information needs
      quickly. The informationists' skills in finding information save the researchers
      time, increase the efficiency of the research team, and complement the
      contributions of other team members. Training by informationists was found
      useful. Informationist services led to increased self-reported library use,
      albeit in some cases this use was entirely via the informationist.  CONCLUSIONS:
      Informationists saved researchers time by obtaining requested information,
      finding esoteric or unfamiliar resources, and providing related training. These
      activities appeared to be facilitated by the acceptance of the informationist as
      part of the research team. This exploratory study provides background that should
      be useful in future, more extensive evaluations.

PMID- 19750183
TI  - Greeting Cards as Data on Social Processes.
AB  - The choices that individuals make when purchasing greeting cards influence what
      designs and sentiments are subsequently available. This suggests that the nature
      of the available greeting cards can be used as an archival data source to gauge
      social attitudes and interpersonal communicative processes. A study is presented
      to illustrate a method in which greeting cards are used to examine how parents
      communicate with their children on special occasions. The advantages and
      disadvantages of the approach are discussed.

PMID- 19750185
TI  - Pedagogical Utilization and Assessment of the Statistic Online Computational
      Resource in Introductory Probability and Statistics Courses.
AB  - Technology-based instruction represents a new recent pedagogical paradigm that is
      rooted in the realization that new generations are much more comfortable with,
      and excited about, new technologies. The rapid technological advancement over the
      past decade has fueled an enormous demand for the integration of modern
      networking, informational and computational tools with classical pedagogical
      instruments. Consequently, teaching with technology typically involves utilizing
      a variety of IT and multimedia resources for online learning, course management,
      electronic course materials, and novel tools of communication, engagement,
      experimental, critical thinking and assessment.The NSF-funded Statistics Online
      Computational Resource (SOCR) provides a number of interactive tools for
      enhancing instruction in various undergraduate and graduate courses in
      probability and statistics. These resources include online instructional
      materials, statistical calculators, interactive graphical user interfaces,
      computational and simulation applets, tools for data analysis and visualization.
      The tools provided as part of SOCR include conceptual simulations and statistical
      computing interfaces, which are designed to bridge between the introductory and
      the more advanced computational and applied probability and statistics courses.
      In this manuscript, we describe our designs for utilizing SOCR technology in
      instruction in a recent study. In addition, present the results of the
      effectiveness of using SOCR tools at two different course intensity levels on
      three outcome measures: exam scores, student satisfaction and choice of
      technology to complete assignments. Learning styles assessment was completed at
      baseline. We have used three very different designs for three different
      undergraduate classes. Each course included a treatment group, using the SOCR
      resources, and a control group, using classical instruction techniques. Our
      findings include marginal effects of the SOCR treatment per individual classes;
      however, pooling the results across all courses and sections, SOCR effects on the
      treatment groups were exceptionally robust and significant. Coupling these
      findings with a clear decrease in the variance of the quantitative examination
      measures in the treatment groups indicates that employing technology, like SOCR,
      in a sound pedagogical and scientific manner enhances overall the students'
      understanding and suggests better long-term knowledge retention.

PMID- 19750184
TI  - Genome-wide association studies for atherosclerotic vascular disease and its risk
      factors.

PMID- 19750186
TI  - Analysis, modeling, and simulation of the accuracy of continuous glucose sensors.
AB  - BACKGROUND: Continuous glucose monitors (CGMs) collect a detailed time series of
      consecutive observations of the underlying process of glucose fluctuations. To
      some extent, however, the high temporal resolution of the data is accompanied by
      increased probability of error in any single data point. Due to both
      physiological and technical reasons, the structure of these errors is complex and
      their analysis is not straightforward. In this article, we describe some of the
      methods needed to obtain a description of the sensor error that is detailed
      enough for simulation. METHODS: Data were provided by Abbott Diabetes Care and
      included two data sets collected by the FreeStyle Navigator(TM) CGM: The first
      set consisted of 1032 time series of glucose readings from 136 patients with type
      1 diabetes and parallel time series of reference blood glucose (BG) collected via
      self-monitoring at irregular intervals. The average duration of a time series was
      5 days; the total number of sensor-reference data pairs was approximately 20,600.
      The second data set consisted of 56 time series of glucose readings from 28
      patients with type 1 diabetes and a parallel time series of reference BG measured
      via the YSI 2300 Stat Plus(TM) analyzer every 15 minutes. The average duration of
      a time series was 2 days; the total number of sensor-reference data pairs was
      approximately 7000. RESULTS: THREE SETS OF RESULTS ARE DISCUSSED: analysis of
      sensor errors with respect to the BG rate of change, mathematical modeling of
      sensor error patterns and distribution, and computer simulation of sensor errors:
      SENSOR ERRORS DEPEND NONLINEARLY ON THE BG RATE OF CHANGE: Errors tend to be
      positive (high readings) when the BG rate of change is negative and negative (low
      readings) when the BG rate of change is positive, which is indicative of an
      underlying time delay. In addition, the sensor noise is non-white (non-Gaussian)
      and the consecutive sensor errors are highly interdependent.Thus, the modeling of
      sensor errors is based on a diffusion model of blood-to-interstitial glucose
      transport, which accounts for the time delay, and a time-series approach, which
      includes autoregressive moving average (ARMA) noise to account for the
      interdependence of consecutive sensor errors.Based on modeling, we have developed
      a computer simulator of sensor errors that includes both generic and sensor
      specific error components. A chi(2) test showed that no significant difference
      exists between the observed and the simulated distribution of sensor errors and
      the distribution of errors of the FreeStyle Navigator (p > .46). CONCLUSIONS: CGM
      accuracy was modeled via diffusion and additive ARMA noise, which allowed for
      designing a computer simulator of sensor errors. The simulator, a component of a
      larger simulation platform approved by the Food and Drug Administration in
      January 2008 for pre-clinical testing of closed-loop strategies, has been
      successfully applied to in silico testing of closed-loop control algorithms,
      resulting in an investigational device exemption for closed-loop trials at the
      University of Virginia.

PMID- 19750187
TI  - Update on Anti-EGFR Therapy.

PMID- 19750188
TI  - Malignant rhabdoid tumour of the liver in the young adult: report of first two
      cases.
AB  - Few cases of malignant rhabdoid tumour (MRT) of the liver are reported in
      literature and always in paediatric patients. We report the first two cases of
      young adults submitted to hepatic resection for MRT of the liver. A major liver
      resection was performed in both cases. The histology showed round or fusiform,
      loosely cohesive cells. The cytoplasm contained abundant eosinophilic inclusions,
      which caused the nuclei to be located in eccentric locations, giving the
      characteristic rhabdoid appearance. The immunohistochemical study was performed,
      and characteristic lack of nuclear INI1 protein expression was found. In a case
      surgery was associated to chemoradiotherapy. One patient died at 48 months
      followup for tumour recurrence. The other is still alive at 25 months followup.
      MRTs are rare tumours of pediatric age with poor prognosis. Hypothetical less
      malignant behaviour in the young adults could be supposed. Therefore an
      aggressive surgical and oncological treatment seems justified.

PMID- 19750189
TI  - Antibiotic-resistant gram negative bacilli in meals delivered at a general
      hospital, Italy.
AB  - This study aimed at detecting the presence of antibiotic-resistant Gram-negatives
      in samples of meals delivered at the University General Hospital of Palermo,
      Italy. Antibiotic resistant Gram negatives were isolated in July-September 2007
      ffrom cold dishes and food contact surfaces and utensils. Bacterial strains were
      submitted to susceptibility test and subtyped by random amplification of
      polymorphic DNA (RAPD). Forty-six of 55 (83.6%) food samples and 14 of 17 (82.3%)
      environmental swabs were culture positive for Gram negative bacilli resistant to
      at least one group of antibacterial drugs. A total of 134 antibiotic resistant
      strains, 51 fermenters and 83 non-fermenters, were recovered. Fermenters and non
      fermenters showed frequencies as high as 97.8% of resistance to two or more
      groups of antibiotics and non fermenters were 28.9% resistant to more than three
      groups. Molecular typing detected 34 different profiles among the fermenters and
      68 among the non-fermenters. Antibiotic resistance was very common among both
      fermenters and non-fermenters. However, the wide heterogeneity of RAPD patterns
      seems to support a prominent role of cross-contamination rather than a clonal
      expansion of a few resistant isolates. A contribution of commensal Gram negatives
      colonizing foods to a common bacterial resistance pool should not been
      overlooked.

PMID- 19750190
TI  - Pilot study of a cell phone-based exercise persistence intervention post
      rehabilitation for COPD.
AB  - OBJECTIVE: To determine the feasibility and efficacy of a six-month, cell phone
      based exercise persistence intervention for patients with chronic obstructive
      pulmonary disease (COPD) following pulmonary rehabilitation. METHODS:
      Participants who completed a two-week run-in were randomly assigned to either
      MOBILE-Coached (n = 9) or MOBILE-Self-Monitored (n = 8). All participants met
      with a nurse to develop an individualized exercise plan, were issued a pedometer
      and exercise booklet, and instructed to continue to log their daily exercise and
      symptoms. MOBILE-Coached also received weekly reinforcement text messages on
      their cell phones; reports of worsening symptoms were automatically flagged for
      follow-up. Usability and satisfaction were assessed. Participants completed
      incremental cycle and six minute walk (6MW) tests, wore an activity monitor for
      14 days, and reported their health-related quality of life (HRQL) at baseline,
      three, and six months. RESULTS: The sample had a mean age of 68 +/-11 and forced
      expiratory volume in one second 18% predicted. Participants reported that logging
      their exercise and symptoms (FEV(1)) of 40 +/- was easy and that keeping track of
      their exercise helped them remain active. There were no differences between
      groups over time in maximal workload, 6MW distance, or HRQL (p > 0.05); however,
      MOBILE-Self-Monitored increased total steps/day whereas MOBILE-Coached logged
      fewer steps over six months (p =0.04). CONCLUSIONS: We showed that it is feasible
      to deliver a cell phone-based exercise persistence intervention to patients with
      COPD post-rehabilitation and that the addition of coaching appeared to be no
      better than self-monitoring. The latter finding needs to be interpreted with
      caution since this was a purely exploratory study. TRIAL REGISTRATION:
      ClinicalTrials.gov (NCT00373932).

PMID- 19750191
TI  - Effects of pulmonary rehabilitation on exercise capacity in patients with COPD: a
      number needed to treat study.
AB  - BACKGROUND: Pulmonary rehabilitation (PR) is recognized as an evidence-based
      treatment in improving dyspnea and quality of life in patients with COPD. We
      evaluated the number needed to treat (NNT) to achieve an increase in physical
      capacity, as defined by a significant improvement in the six-minute walk test
      (6MWT) in patients with COPD undergoing PR. METHODS: The study enrolled 284
      patients aged 41 to 86 years (mean age 69.4 years) divided into two groups: a
      study group (222 patients) undergoing a PR program, and a control group (62
      patients) treated only with drugs. The study group included patients with COPD
      divided in four subgroups according to GOLD stages. RESULTS: In the study group,
      142 out of 222 patients (64%) had an increase of at least 54 m in the 6MWT
      following PR versus 8 out of 62 patients (13%) in the control group after the
      same time interval. The NNT in the overall study group was 2; the same NNT was
      obtained in GOLD stages 2, 3, and 4, but was 8 in stage 1. CONCLUSIONS: PR is
      highly effective in improving the exercise capacity of patients with COPD, as
      demonstrated by a valuable NNT, with better results in patients with a more
      severe disease.

PMID- 19750193
TI  - Ion channels to inactivate neurons in Drosophila.
AB  - Ion channels are the determinants of excitability; therefore, manipulation of
      their levels and properties provides an opportunity for the investigator to
      modulate neuronal and circuit function. There are a number of ways to suppress
      electrical activity in Drosophila neurons, for instance, over-expression of
      potassium channels (i.e. Shaker Kv1, Shaw Kv3, Kir2.1 and DORK) that are open at
      resting membrane potential. This will result in increased potassium efflux and
      membrane hyperpolarisation setting resting membrane potential below the threshold
      required to fire action potentials. Alternatively over-expression of other
      channels, pumps or co-transporters that result in a hyperpolarised membrane
      potential will also prevent firing. Lastly, neurons can be inactivated by,
      disrupting or reducing the level of functional voltage-gated sodium (Nav1
      paralytic) or calcium (Cav2 cacophony) channels that mediate the depolarisation
      phase of action potentials. Similarly, strategies involving the opposite channel
      manipulation should allow net depolarisation and hyperexcitation in a given
      neuron. These changes in ion channel expression can be brought about by the
      versatile transgenic (i.e. Gal4/UAS based) systems available in Drosophila
      allowing fine temporal and spatial control of (channel) transgene expression.
      These systems are making it possible to electrically inactivate (or hyperexcite)
      any neuron or neural circuit in the fly brain, and much like an exquisite lesion
      experiment, potentially elucidate whatever interesting behaviour or phenotype
      each network mediates. These techniques are now being used in Drosophila to
      reprogram electrical activity of well-defined circuits and bring about robust and
      easily quantifiable changes in behaviour, allowing different models and
      hypotheses to be rapidly tested.

PMID- 19750194
TI  - Automated recognition of brain region mentions in neuroscience literature.
AB  - The ability to computationally extract mentions of neuroanatomical regions from
      the literature would assist linking to other entities within and outside of an
      article. Examples include extracting reports of connectivity or region-specific
      gene expression. To facilitate text mining of neuroscience literature we have
      created a corpus of manually annotated brain region mentions. The corpus contains
      1,377 abstracts with 18,242 brain region annotations. Interannotator agreement
      was evaluated for a subset of the documents, and was 90.7% and 96.7% for strict
      and lenient matching respectively. We observed a large vocabulary of over 6,000
      unique brain region terms and 17,000 words. For automatic extraction of brain
      region mentions we evaluated simple dictionary methods and complex natural
      language processing techniques. The dictionary methods based on neuroanatomical
      lexicons recalled 36% of the mentions with 57% precision. The best performance
      was achieved using a conditional random field (CRF) with a rich feature set.
      Features were based on morphological, lexical, syntactic and contextual
      information. The CRF recalled 76% of mentions at 81% precision, by counting
      partial matches recall and precision increase to 86% and 92% respectively. We
      suspect a large amount of error is due to coordinating conjunctions, previously
      unseen words and brain regions of less commonly studied organisms. We found
      context windows, lemmatization and abbreviation expansion to be the most
      informative techniques. The corpus is freely available at
      http://www.chibi.ubc.ca/WhiteText/.

PMID- 19750192
TI  - Targeted treatment in COPD: a multi-system approach for a multi-system disease.
AB  - Chronic obstructive pulmonary disease is a varied condition when examined from a
      number of different perspectives including factors which influence disease
      development, pathological process and clinical features. There may be a complex
      interaction between the degree by which each of these processes influences the
      development of COPD and the subsequent clinical phenotype with which the patient
      presents. The varied host response and subsequent clinical phenotype has
      generated much interest in recent years. It is possible that failure of treatment
      to impact on mortality and reverse the disease process is because of the
      heterogeneous nature of the condition. Identification and targeted treatment of
      clinical and pathological phenotypes within the broad spectrum of COPD may
      therefore improve outcome. This article will review previous work which has
      attempted to phenotype COPD and identify if specific treatment for these
      phenotypes has been shown to be of benefit. It will examine the work on
      pathological processes and clinical manifestations, both pulmonary and systemic,
      and will focus on pharmacological therapies.

PMID- 19750195
TI  - Enduring neurobehavioral effects of early life trauma mediated through learning
      and corticosterone suppression.
AB  - Early life trauma alters later life emotions, including fear. To better
      understand mediating mechanisms, we subjected pups to either predictable or
      unpredictable trauma, in the form of paired or unpaired odor-0.5 mA shock
      conditioning which, during a sensitive period, produces an odor preference and no
      learning respectively. Fear conditioning and its neural correlates were then
      assessed after the sensitive period at postnatal day (PN)13 or in adulthood, ages
      when amygdala-dependent fear occurs. Our results revealed that paired odor-shock
      conditioning starting during the sensitive period (PN8-12) blocked fear
      conditioning in older infants (PN13) and pups continued to express olfactory bulb
      dependent odor preference learning. This PN13 fear learning inhibition was also
      associated with suppression of shock-induced corticosterone, although the age
      appropriate amygdala-dependent fear learning was reinstated with systemic
      corticosterone (3 mg/kg) during conditioning. On the other hand, sensitive period
      odor-shock conditioning did not prevent adult fear conditioning, although
      freezing, amygdala and hippocampal 2-DG uptake and corticosterone levels were
      attenuated compared to adult conditioning without infant conditioning. Normal
      levels of freezing, amygdala and hippocampal 2-DG uptake were induced with
      systemic corticosterone (5 mg/kg) during adult conditioning. These results
      suggest that the contingency of early life trauma mediates at least some effects
      of early life stress through learning and suppression of corticosterone levels.
      However, developmental differences between infants and adults are expressed with
      PN13 infants' learning consistent with the original learned preference, while
      adult conditioning overrides the original learned preference with attenuated
      amygdala-dependent fear learning.

PMID- 19750196
TI  - Platelet factor 4 is highly upregulated in dendritic cells after severe trauma.
AB  - Dendritic cells (DCs) represent an important linkage between the innate and
      adaptive immune system and express proinflammatory transcriptomic products early
      after trauma. The use of a genomic approach recently revealed that platelet
      factor 4 (PF4) is significantly upregulated in DCs in patients after multiple
      trauma. However, knowledge about subsequent PF4 alteration and its potential
      clinical relevance in the context of multiple trauma is still limited. We used
      quantitative reverse transcription-polymerase chain reaction to analyze PF4
      expression in both myeloid DCs (MDCs) and plasmocytoid DCs (PDCs) isolated from
      10 patients after multiple trauma. Intracellular PF4 as well as HLA-DR expression
      were detected by flow cytometry. Furthermore, DCs and peripheral blood
      mononuclear cells were incubated on a monolayer of human umbilical endothelial
      cells and their adhesion properties were analyzed. The ratio of the DC subtypes
      (MDC and PDC) was assessed by flow cytometry. PF4 expression significantly
      increased on d 1 and d 2 as measured by reverse transcription-polymerase chain
      reaction. Intracellular PF4 content in MDCs and PDCs was significantly elevated
      in trauma patients compared with healthy controls. In addition, the surface
      antigen HLA-DR on MDCs was significantly elevated on d 1 and d 4 after trauma in
      patients compared with controls. However, cell adhesion of DCs did not show any
      significant differences between patients and controls. PF4 concentration in MDCs
      and PDCs significantly correlated with the injury severity score. These results
      confirm an early and subsequent posttraumatic activation of PF4 in DCs. PF4 also
      participates in the posttraumatic activation of DCs in relation to injury
      severity, a role that might be preferably based on the modification of receptor
      expression, whereas adhesion properties are largely unaffected.

PMID- 19750197
TI  - Counteracting incentive sensitization in severe alcohol dependence using deep
      brain stimulation of the nucleus accumbens: clinical and basic science aspects.
AB  - The ventral striatum/nucleus accumbens (NAcc) has been implicated in the craving
      for drugs and alcohol which is a major reason for relapse of addicted people.
      Craving might be induced by drug-related cues. This suggests that disruption of
      craving-related neural activity in the NAcc may significantly reduce craving in
      alcohol-dependent patients. Here we report on preliminary clinical and
      neurophysiological evidence in three male patients who were treated with high
      frequency deep brain stimulation of the NAcc bilaterally. All three had been
      alcohol-dependent for many years, unable to abstain from drinking, and had
      experienced repeated relapses prior to the stimulation. After the operation,
      craving was greatly reduced and all three patients were able to abstain from
      drinking for extended periods of time. Immediately after the operation but prior
      to connection of the stimulation electrodes to the stimulator, local field
      potentials were obtained from the externalized cables in two patients while they
      performed cognitive tasks addressing action monitoring and incentive salience of
      drug-related cues. LFPs in the action monitoring task provided further evidence
      for a role of the NAcc in goal-directed behaviors. Importantly, alcohol-related
      cue stimuli in the incentive salience task modulated LFPs even though these cues
      were presented outside of the attentional focus. This implies that cue-related
      craving involves the NAcc and is highly automatic.

PMID- 19750198
TI  - Neural activity changes underlying the working memory deficit in alpha-CaMKII
      heterozygous knockout mice.
AB  - The alpha-isoform of calcium/calmodulin-dependent protein kinase II (alpha
      CaMKII) is expressed abundantly in the forebrain and is considered to have an
      essential role in synaptic plasticity and cognitive function. Previously, we
      reported that mice heterozygous for a null mutation of alpha-CaMKII (alpha
      CaMKII+/-) have profoundly dysregulated behaviors including a severe working
      memory deficit, which is an endophenotype of schizophrenia and other psychiatric
      disorders. In addition, we found that almost all the neurons in the dentate gyrus
      (DG) of the mutant mice failed to mature at molecular, morphological and
      electrophysiological levels. In the present study, to identify the brain
      substrates of the working memory deficit in the mutant mice, we examined the
      expression of the immediate early genes (IEGs), c-Fos and Arc, in the brain after
      a working memory version of the eight-arm radial maze test. c-Fos expression was
      abolished almost completely in the DG and was reduced significantly in neurons in
      the CA1 and CA3 areas of the hippocampus, central amygdala, and medial prefrontal
      cortex (mPFC). However, c-Fos expression was intact in the entorhinal and visual
      cortices. Immunohistochemical studies using arc promoter driven dVenus transgenic
      mice demonstrated that arc gene activation after the working memory task occurred
      in mature, but not immature neurons in the DG of wild-type mice. These results
      suggest crucial insights for the neural circuits underlying spatial mnemonic
      processing during a working memory task and suggest the involvement of alpha
      CaMKII in the proper maturation and integration of DG neurons into these
      circuits.

PMID- 19750199
TI  - A brain-machine interface instructed by direct intracortical microstimulation.
AB  - Brain-machine interfaces (BMIs) establish direct communication between the brain
      and artificial actuators. As such, they hold considerable promise for restoring
      mobility and communication in patients suffering from severe body paralysis. To
      achieve this end, future BMIs must also provide a means for delivering sensory
      signals from the actuators back to the brain. Prosthetic sensation is needed so
      that neuroprostheses can be better perceived and controlled. Here we show that a
      direct intracortical input can be added to a BMI to instruct rhesus monkeys in
      choosing the direction of reaching movements generated by the BMI. Somatosensory
      instructions were provided to two monkeys operating the BMI using either: (a)
      vibrotactile stimulation of the monkey's hands or (b) multi-channel intracortical
      microstimulation (ICMS) delivered to the primary somatosensory cortex (S1) in one
      monkey and posterior parietal cortex (PP) in the other. Stimulus delivery was
      contingent on the position of the computer cursor: the monkey placed it in the
      center of the screen to receive machine-brain recursive input. After 2 weeks of
      training, the same level of proficiency in utilizing somatosensory information
      was achieved with ICMS of S1 as with the stimulus delivered to the hand skin.
      ICMS of PP was not effective. These results indicate that direct, bi-directional
      communication between the brain and neuroprosthetic devices can be achieved
      through the combination of chronic multi-electrode recording and microstimulation
      of S1. We propose that in the future, bidirectional BMIs incorporating ICMS may
      become an effective paradigm for sensorizing neuroprosthetic devices.

PMID- 19750200
TI  - Effects of early psychosocial deprivation on the development of memory and
      executive function.
AB  - This study investigated the effects of early institutional care on memory and
      executive functioning. Subjects were participants in the Bucharest Early
      Intervention Project (BEIP) and included institutionalized children, children
      with a history of institutionalization who were assigned to a foster care
      intervention, and community children in Bucharest, Romania. Memory and executive
      functioning were assessed at the age of 8 years using the Cambridge
      Neuropsychological Test and Automated Battery (CANTAB). As expected, children
      with a history of early institutional care performed worse on measures of both
      visual memory and executive functioning compared to their peers without a history
      of institutional care. In comparing children randomly assigned to the foster care
      intervention with their peers who had continued care in the institution, initial
      comparisons did not show significant differences on any of the memory or
      executive functioning outcomes. However, for one of the measures of executive
      functioning, after controlling for birth weight, head circumference, and duration
      of time spent in early institutional care, the foster care intervention was a
      significant predictor of scores. These results support and extend previous
      findings of deficits in memory and executive functioning among school-age
      children with a history of early deprivation due to institutional care. This
      study has implications for the millions of children who continue to experience
      the psychosocial deprivation associated with early institutional care.

PMID- 19750201
TI  - Does abnormal sleep impair memory consolidation in schizophrenia?
AB  - Although disturbed sleep is a prominent feature of schizophrenia, its relation to
      the pathophysiology, signs, and symptoms of schizophrenia remains poorly
      understood. Sleep disturbances are well known to impair cognition in healthy
      individuals. Yet, in spite of its ubiquity in schizophrenia, abnormal sleep has
      generally been overlooked as a potential contributor to cognitive deficits.
      Amelioration of cognitive deficits is a current priority of the schizophrenia
      research community, but most efforts to define, characterize, and quantify
      cognitive deficits focus on cross-sectional measures. While this approach
      provides a valid snapshot of function, there is now overwhelming evidence that
      critical aspects of learning and memory consolidation happen offline, both over
      time and with sleep. Initial memory encoding is followed by a prolonged period of
      consolidation, integration, and reorganization, that continues over days or even
      years. Much of this evolution of memories is mediated by sleep. This article
      briefly reviews (i) what is known about abnormal sleep in schizophrenia, (ii)
      sleep-dependent memory consolidation in healthy individuals, (iii) recent
      findings of impaired sleep-dependent memory consolidation in schizophrenia, and
      (iv) implications of impaired sleep-dependent memory consolidation in
      schizophrenia. This literature suggests that abnormal sleep in schizophrenia
      disrupts attention and impairs sleep-dependent memory consolidation and task
      automation. We conclude that these sleep-dependent impairments may contribute
      substantially to generalized cognitive deficits in schizophrenia. Understanding
      this contribution may open new avenues to ameliorating cognitive dysfunction and
      thereby improve outcome in schizophrenia.

PMID- 19750202
TI  - Salivary Diagnostics: Amazing as it might seem, doctors can detect and monitor
      diseases using molecules found in a sample of spit.

PMID- 19750203
TI  - Optically actuated thermocapillary movement of gas bubbles on an absorbing
      substrate.
AB  - The authors demonstrate an optical manipulation mechanism of gas bubbles for
      microfluidic applications. Air bubbles in a silicone oil medium are manipulated
      via thermocapillary forces generated by the absorption of a laser in an amorphous
      silicon thin film. In contrast to previous demonstrations of optically controlled
      thermally driven bubble movement, transparent liquids can be used, as the thermal
      gradient is formed from laser absorption in the amorphous silicon substrate, and
      not in the liquid. A variety of bubbles with volumes ranging from 19 pl to 23 nl
      was transported at measured velocities of up to 1.5 mm/s.

PMID- 19750204
TI  - Functional Neuroimaging Insights Into the Development of Skilled Reading.
AB  - Typically developing children require years of overt training and practice to
      learn to read with skill. The relatively recent advent of functional neuroimaging
      methods amenable to the study of children has provided insight into the
      neurobiological underpinnings of skilled reading development. In this brief
      review, we discuss how neuroimaging during reading-related tasks has revealed
      that, when adult and child skilled readers perform identical reading-related
      tasks with comparable levels of performance, these groups show similar, but
      nonidentical patterns of regional brain activity. Children activate some neural
      regions that adults do not activate (or activate less), and vice versa. The
      activity patterns in these regions transition to mature levels with increased
      proficiency and maturity. The dynamic nature of the reading brain as the child
      matures is thought to be a demonstration of both the inherent flexibility and the
      increasing efficiency of brain processing over development.

PMID- 19750205
TI  - Serum Alkaline Phosphatase Level as a Prognostic Tool in Colorectal Cancer: A
      Study of 105 patients.
AB  - BACKGROUND: Serum alkaline phosphotase (ALP) levels are frequently elevated in
      patients with metastatic colorectal cancer (CRC). However, the significance of
      ALP in terms of detecting hepatic metastasis or prognosis is not well
      established.  MATERIALS AND METHODS: Medical records of patients with CRC seen at
      University of Alabama at Birmingham (UAB) (1998-2002) were reviewed and
      statistical analysis was done to evaluate the significance of ALP as a prognostic
      tool. The normal range for ALP was quantified at 39 U/L to 117 U/L. Change in ALP
      levels over time (defined as time interval between two cycles; such as 4 weeks
      for Mayo regimen, 8 weeks for Roswell Park regimen and 6 weeks for IFL regimen)
      was categorized as large (120+ U/L), medium (20-119 U/L), and minimal (< 20 U/L).
      RESULTS: A total of 105 patients with eligible medical records were identified
      (Mean age: 59 yrs; 53% male; Staging: II: 43 patients, III: 31 patients, IV: 32
      patients). Increasing ALP levels correlated with increasing stage (Mean: I = 116,
      II = 219, III = 302; P = 0.0003). ALP levels were elevated in 74% of patients
      with liver metastases (Mean, 290) and in 33% without liver metastases (Mean, 122)
      (P = 0.001). Patients with elevated ALP levels at the most recent time of
      progression were 5.7 (95% CI, 2.4-13.3) times more likely to have a liver
      metastases compared to patients with normal levels. Additionally, patients with
      elevated ALP levels at their most recent visit were 4.2 (95% CI, 1.7-10.7) times
      more likely to have a worse prognosis compared to patients with normal levels.
      However, after controlling for the effects of liver metastases, the association
      between elevated levels and prognosis was no longer significant. After
      controlling for the effects of age, sex, and liver metastases, large changes in
      AP levels were associated with a 4.4 (95% CI, 1.0-19.1) times greater odds of
      having a worse prognosis compared to patients with a minimal change. Patients
      with an ALP level greater than 160 were 12 (95% CI, 4.3-33.3) times more likely
      to have liver metastases than patients with an ALP level of less than 160. Mean
      CEA level was 78 for patients without liver metastases and 308 for patients with
      liver metastases. CEA levels were compared against ALP in a random sample of 18
      patients, which revealed a correlation between increasing levels of CEA (.002)
      with increasing levels of ALP.  CONCLUSION: Instead of the upper normal limit for
      ALP, our data shows that using an ALP cutoff of 160 U/L increases the sensitivity
      of liver metastases detection. Also, a change in ALP levels of greater than 120
      U/L over four-to-six weeks may be indicative of disease progression. Monitoring
      ALP is a simple, low cost, and relatively sensitive screening tool. Prospective
      studies involving evaluation of ALP in addition to CEA in patients with CRC is
      indicated.

PMID- 19750206
TI  - Cell-based Assays to Identify Inhibitors of Viral Disease.
AB  - BACKGROUND: Antagonizing the production of infectious virus inside cells requires
      drugs that can cross the cell membrane without harming host cells. OBJECTIVE: It
      is therefore advantageous to establish intracellular potency of anti-viral drug
      candidates early in the drug-discovery pipeline. METHODS: To this end, cell-based
      assays are being developed and employed in high-throughput drug screening,
      ranging from assays that monitor replication of intact viruses to those that
      monitor activity of specific viral proteins. While numerous cell-based assays
      have been developed and investigated, rapid counter screens are also needed to
      define the specific viral targets of identified inhibitors and to eliminate
      nonspecific screening hits. RESULTS/CONCLUSIONS: Here, we describe the types of
      cell-based assays being used in antiviral drug screens and evaluate the equally
      important counter screens that are being employed to reach the full potential of
      cell-based high-throughput screening.

PMID- 19750207
TI  - Monolayer Formation on Silicon and Mica Surfaces Rearranged from N-Hexadecanoyl-l
      alanine Supramolecular Structures.
AB  - The rearrangements of N-hexadecanoyl-l-alanine supramolecular structures in water
      to form monolayers on silicon and mica surfaces have been investigated using
      atomic force microscopy. It is the first time that such a monolayer with the
      polar groups on the solid surface and the alkyl chains up is obtained through a
      rational molecular design. The monolayer formation results from the strong
      interaction between the molecular headgroups and the surface, the intermolecular
      hydrogen bonding interaction via a six-membered ring structure in the case of
      silicon surfaces, and the additional attractive force in the case of mica
      surfaces. The anisotropic and dendritic growth structures, clearly observed for
      the monolayers rearranged on mica surfaces, are indicative of a homochiral
      effect. The differences in height and morphology of the monolayers on the two
      types of surfaces are considered to be relevant to the surface roughness and to
      the interactions between the molecules and the surface.

PMID- 19750208
TI  - Single cell analysis of complex thymus stromal cell populations: rapid thymic
      epithelia preparation characterizes radiation injury.
AB  - Thymic epithelial cells (TECs) and dendritic cells are essential for the
      maintenance of thymopoiesis. Because these stromal elements define the progenitor
      niche, provide critical survival signals and growth factors, and direct positive
      and negative selection, detailed study of these populations is necessary to
      understand important elements for thymic renewal after cytotoxic injury. Study of
      TEC is currently hindered by lengthy enzymatic separation techniques with
      decreased viability. We present a new rapid separation technique that yields
      consistent viable TEC numbers in a quarter of the prior preparation time. Using
      this new procedure, we identify changes in stroma populations following total
      body irradiation (TBI). By flow cytometry, we show that TBI significantly
      depletes UEA+ medullary TEC, while sparing Ly51+ CD45- cells. Further
      characterization of the Ly51+ subset reveals enrichment of fibroblasts (CD45-
      Ly51+ MHCII-), while cortical TECs (CD45- Ly51+ MHCII+) were markedly reduced.
      Dendritic cells (CD11lc+ CD45+) were also decreased following TBI. These data
      suggest that cytotoxic preparative regimens may impair thymic renewal by reducing
      critical populations of cortical and medullary TEC, and that such thymic damage
      can be assessed by this new rapid separation technique, thereby providing a means
      of assessing optimal conditioning pretransplantfor enhancing thymic-dependent
      immune reconstitution posttranspiant.

PMID- 19750209
TI  - Gaussian predictive process models for large spatial data sets.
AB  - With scientific data available at geocoded locations, investigators are
      increasingly turning to spatial process models for carrying out statistical
      inference. Over the last decade, hierarchical models implemented through Markov
      chain Monte Carlo methods have become especially popular for spatial modelling,
      given their flexibility and power to fit models that would be infeasible with
      classical methods as well as their avoidance of possibly inappropriate
      asymptotics. However, fitting hierarchical spatial models often involves
      expensive matrix decompositions whose computational complexity increases in cubic
      order with the number of spatial locations, rendering such models infeasible for
      large spatial data sets. This computational burden is exacerbated in multivariate
      settings with several spatially dependent response variables. It is also
      aggravated when data are collected at frequent time points and spatiotemporal
      process models are used. With regard to this challenge, our contribution is to
      work with what we call predictive process models for spatial and spatiotemporal
      data. Every spatial (or spatiotemporal) process induces a predictive process
      model (in fact, arbitrarily many of them). The latter models project process
      realizations of the former to a lower dimensional subspace, thereby reducing the
      computational burden. Hence, we achieve the flexibility to accommodate non
      stationary, non-Gaussian, possibly multivariate, possibly spatiotemporal
      processes in the context of large data sets. We discuss attractive theoretical
      properties of these predictive processes. We also provide a computational
      template encompassing these diverse settings. Finally, we illustrate the approach
      with simulated and real data sets.

PMID- 19750210
TI  - Windei, the Drosophila homolog of mAM/MCAF1, is an essential cofactor of the H3K9
      methyl transferase dSETDB1/Eggless in germ line development.
AB  - The epigenetic regulation of gene expression by the covalent modification of
      histones is a fundamental mechanism required for the proper differentiation of
      germ line cells during development. Trimethylation of histone 3 lysine 9
      (H3K9me3) leads to chromatin silencing and the formation of heterochromatin by
      recruitment of heterochromatin protein 1 (HP1). dSETDB1/Eggless (Egg), the
      ortholog of the human methyltransferase SETDB1, is the only essential H3K9
      methyltransferase in Drosophila and is required for H3K9 trimethylation in the
      female germ line. Here we show that Windei (Wde), the Drosophila homolog of mouse
      mAM and human MCAF1, is an essential cofactor of Egg required for its nuclear
      localization and function in female germ line cells. By deletion analysis
      combined with coimmunoprecipitation, we have identified the protein regions in
      Wde and Egg that are necessary and sufficient for the interaction between the two
      proteins. We furthermore identified a region of Egg that gets covalently modified
      by SUMOylation, which may facilitate the formation of higher order chromatin
      modifying complexes. Together with Egg, Wde localizes to euchromatin, is enriched
      on chromosome 4, and binds to the Painting of fourth (POF) protein. Our data
      provide the first genetic and phenotypic analysis of a mAM/MCAF1 homolog in a
      model organism and demonstrate its essential function in the survival of germ
      line cells.

PMID- 19750211
TI  - Parallel computational subunits in dentate granule cells generate multiple place
      fields.
AB  - A fundamental question in understanding neuronal computations is how dendritic
      events influence the output of the neuron. Different forms of integration of
      neighbouring and distributed synaptic inputs, isolated dendritic spikes and local
      regulation of synaptic efficacy suggest that individual dendritic branches may
      function as independent computational subunits. In the present paper, we study
      how these local computations influence the output of the neuron. Using a simple
      cascade model, we demonstrate that triggering somatic firing by a relatively
      small dendritic branch requires the amplification of local events by dendritic
      spiking and synaptic plasticity. The moderately branching dendritic tree of
      granule cells seems optimal for this computation since larger dendritic trees
      favor local plasticity by isolating dendritic compartments, while reliable
      detection of individual dendritic spikes in the soma requires a low branch
      number. Finally, we demonstrate that these parallel dendritic computations could
      contribute to the generation of multiple independent place fields of hippocampal
      granule cells.

PMID- 19750212
TI  - Fast mapping of short sequences with mismatches, insertions and deletions using
      index structures.
AB  - With few exceptions, current methods for short read mapping make use of simple
      seed heuristics to speed up the search. Most of the underlying matching models
      neglect the necessity to allow not only mismatches, but also insertions and
      deletions. Current evaluations indicate, however, that very different error
      models apply to the novel high-throughput sequencing methods. While the most
      frequent error-type in Illumina reads are mismatches, reads produced by 454's GS
      FLX predominantly contain insertions and deletions (indels). Even though 454
      sequencers are able to produce longer reads, the method is frequently applied to
      small RNA (miRNA and siRNA) sequencing. Fast and accurate matching in particular
      of short reads with diverse errors is therefore a pressing practical problem. We
      introduce a matching model for short reads that can, besides mismatches, also
      cope with indels. It addresses different error models. For example, it can handle
      the problem of leading and trailing contaminations caused by primers and poly-A
      tails in transcriptomics or the length-dependent increase of error rates. In
      these contexts, it thus simplifies the tedious and error-prone trimming step. For
      efficient searches, our method utilizes index structures in the form of enhanced
      suffix arrays. In a comparison with current methods for short read mapping, the
      presented approach shows significantly increased performance not only for 454
      reads, but also for Illumina reads. Our approach is implemented in the software
      segemehl available at http://www.bioinf.uni-leipzig.de/Software/segemehl/.

PMID- 19750213
TI  - Witnessing a natural, safe, and healthy birth.
AB  - In this column, the editor of The Journal of Perinatal Education discusses her
      experience witnessing a natural, safe, and healthy home birth. The editor also
      describes the contents of this issue, which offer a broad range of resources,
      research, and inspiration for childbirth educators in their efforts to promote
      normal birth.

PMID- 19750214
TI  - Safe, healthy birth: what every pregnant woman needs to know.
AB  - In spite of technology and medical science's ability to manage complex health
      problems, the current maternity care environment has increased risks for healthy
      women and their babies. It comes as a surprise to most women that standard
      maternity care does not reflect best scientific evidence. In this column,
      evidence-based maternity care practices are discussed with an emphasis on the
      practices that increase safety for mother and baby, and what pregnant women need
      to know in order to have safe, healthy births is described.

PMID- 19750215
TI  - Fine pathogen discrimination within the APL1 gene family protects Anopheles
      gambiae against human and rodent malaria species.
AB  - Genetically controlled resistance of Anopheles gambiae mosquitoes to Plasmodium
      falciparum is a common trait in the natural population, and a cluster of natural
      resistance loci were mapped to the Plasmodium-Resistance Island (PRI) of the A.
      gambiae genome. The APL1 family of leucine-rich repeat (LRR) proteins was
      highlighted by candidate gene studies in the PRI, and is comprised of paralogs
      APL1A, APL1B and APL1C that share > or =50% amino acid identity. Here, we present
      a functional analysis of the joint response of APL1 family members during
      mosquito infection with human and rodent Plasmodium species. Only paralog APL1A
      protected A. gambiae against infection with the human malaria parasite P.
      falciparum from both the field population and in vitro culture. In contrast, only
      paralog APL1C protected against the rodent malaria parasites P. berghei and P.
      yoelii. We show that anti-P. falciparum protection is mediated by the Imd/Rel2
      pathway, while protection against P. berghei infection was shown to require
      Toll/Rel1 signaling. Further, only the short Rel2-S isoform and not the long Rel2
      F isoform of Rel2 confers protection against P. falciparum. Protection correlates
      with the transcriptional regulation of APL1A by Rel2-S but not Rel2-F, suggesting
      that the Rel2-S anti-parasite phenotype results at least in part from its
      transcriptional control over APL1A. These results indicate that distinct members
      of the APL1 gene family display a mutually exclusive protective effect against
      different classes of Plasmodium parasites. It appears that a gene-for-pathogen
      class system orients the appropriate host defenses against distinct categories of
      similar pathogens. It is known that insect innate immune pathways can distinguish
      between grossly different microbes such as Gram-positive bacteria, Gram-negative
      bacteria, or fungi, but the function of the APL1 paralogs reveals that mosquito
      innate immunity possesses a more fine-grained capacity to distinguish between
      classes of closely related eukaryotic pathogens than has been previously
      recognized.

PMID- 19750216
TI  - The Aurora Kinase in Trypanosoma brucei plays distinctive roles in metaphase
      anaphase transition and cytokinetic initiation.
AB  - Aurora B kinase is an essential regulator of chromosome segregation with the
      action well characterized in eukaryotes. It is also implicated in cytokinesis,
      but the detailed mechanism remains less clear, partly due to the difficulty in
      separating the latter from the former function in a growing cell. A chemical
      genetic approach with an inhibitor of the enzyme added to a synchronized cell
      population at different stages of the cell cycle would probably solve this
      problem. In the deeply branched parasitic protozoan Trypanosoma brucei, an Aurora
      B homolog, TbAUK1, was found to control both chromosome segregation and
      cytokinetic initiation by evidence from RNAi and dominant negative mutation. To
      clearly separate these two functions, VX-680, an inhibitor of TbAUK1, was added
      to a synchronized T. brucei procyclic cell population at different cell cycle
      stages. The unique trans-localization pattern of the chromosomal passenger
      complex (CPC), consisting of TbAUK1 and two novel proteins TbCPC1 and TbCPC2, was
      monitored during mitosis and cytokinesis by following the migration of the
      proteins tagged with enhanced yellow fluorescence protein in live cells with time
      lapse video microscopy. Inhibition of TbAUK1 function in S-phase, prophase or
      metaphase invariably arrests the cells in the metaphase, suggesting an action of
      TbAUK1 in promoting metaphase-anaphase transition. TbAUK1 inhibition in anaphase
      does not affect mitotic exit, but prevents trans-localization of the CPC from the
      spindle midzone to the anterior tip of the new flagellum attachment zone for
      cytokinetic initiation. The CPC in the midzone is dispersed back to the two
      segregated nuclei, while cytokinesis is inhibited. In and beyond telophase,
      TbAUK1 inhibition has no effect on the progression of cytokinesis or the
      subsequent G1, S and G2 phases until a new metaphase is attained. There are thus
      two clearly distinct points of TbAUK1 action in T. brucei: the metaphase-anaphase
      transition and cytokinetic initiation. This is the first time to our knowledge
      that the dual functions of an Aurora B homolog is dissected and separated into
      two clearly distinct time frames in a cell cycle.

PMID- 19750217
TI  - Quantitation of human seroresponsiveness to Merkel cell polyomavirus.
AB  - Merkel cell carcinoma (MCC) is a relatively uncommon but highly lethal form of
      skin cancer. A majority of MCC tumors carry DNA sequences derived from a newly
      identified virus called Merkel cell polyomavirus (MCV or MCPyV), a candidate
      etiologic agent underlying the development of MCC. To further investigate the
      role of MCV infection in the development of MCC, we developed a reporter vector
      based neutralization assay to quantitate MCV-specific serum antibody responses in
      human subjects. Our results showed that 21 MCC patients whose tumors harbored MCV
      DNA all displayed vigorous MCV-specific antibody responses. Although 88% (42/48)
      of adult subjects without MCC were MCV seropositive, the geometric mean titer of
      the control group was 59-fold lower than the MCC patient group (p<0.0001). Only
      4% (2/48) of control subjects displayed neutralizing titers greater than the mean
      titer of the MCV-positive MCC patient population. MCC tumors were found not to
      express detectable amounts of MCV VP1 capsid protein, suggesting that the strong
      humoral responses observed in MCC patients were primed by an unusually
      immunogenic MCV infection, and not by viral antigen expressed by the MCC tumor
      itself. The occurrence of highly immunogenic MCV infection in MCC patients is
      unlikely to reflect a failure to control polyomavirus infections in general, as
      seroreactivity to BK polyomavirus was similar among MCC patients and control
      subjects. The results support the concept that MCV infection is a causative
      factor in the development of most cases of MCC. Although MCC tumorigenesis can
      evidently proceed in the face of effective MCV-specific antibody responses, a
      small pilot animal immunization study revealed that a candidate vaccine based on
      MCV virus-like particles (VLPs) elicits antibody responses that robustly
      neutralize MCV reporter vectors in vitro. This suggests that a VLP-based vaccine
      could be effective for preventing the initial establishment of MCV infection.

PMID- 19750218
TI  - The Chlamydia type III secretion system C-ring engages a chaperone-effector
      protein complex.
AB  - In Gram-negative bacterial pathogens, specialized chaperones bind to secreted
      effector proteins and maintain them in a partially unfolded form competent for
      translocation by type III secretion systems/injectisomes. How diverse sets of
      effector-chaperone complexes are recognized by injectisomes is unclear. Here we
      describe a new mechanism of effector-chaperone recognition by the Chlamydia
      injectisome, a unique and ancestral line of these evolutionarily conserved
      secretion systems. By yeast two-hybrid analysis we identified networks of
      Chlamydia-specific proteins that interacted with the basal structure of the
      injectisome, including two hubs of protein-protein interactions that linked known
      secreted effector proteins to CdsQ, the putative cytoplasmic C-ring component of
      the secretion apparatus. One of these protein-interaction hubs is defined by
      Ct260/Mcsc (Multiple cargo secretion chaperone). Mcsc binds to and stabilizes at
      least two secreted hydrophobic proteins, Cap1 and Ct618, that localize to the
      membrane of the pathogenic vacuole ("inclusion"). The resulting complexes bind to
      CdsQ, suggesting that in Chlamydia, the C-ring of the injectisome mediates the
      recognition of a subset of inclusion membrane proteins in complex with their
      chaperone. The selective recognition of inclusion membrane proteins by chaperones
      may provide a mechanism to co-ordinate the translocation of subsets of inclusion
      membrane proteins at different stages in infection.

PMID- 19750219
TI  - The role of specific checkpoint-induced S-phase transcripts in resistance to
      replicative stress.
AB  - Checkpoint activation during S phase modulates transcription. In response to
      replication arrest, the fission yeast Cds1 checkpoint kinase maintains the normal
      S-phase transcriptional program by regulating MBF, the S-phase transcription
      factor. We show that similar regulation occurs in response to DNA damage during S
      phase. We test the relative contributions to replication-stress resistance of
      transcriptional regulation and the two other major checkpoint functions: cell
      cycle arrest and fork stabilization. We show that, although transcriptional
      regulation provides only modest resistance relative to fork stabilization, it
      contributes significantly to cell survival. Finally, we investigate the roles of
      two specific transcripts: mik1 and mrc1. These results demonstrate the general
      importance of checkpoint regulation of G1/S transcription in response to
      replicative stress and elucidate the specific roles of Mik1 and Mrc1 in the
      checkpoint.

PMID- 19750220
TI  - Modeling and analysis of the molecular basis of pain in sensory neurons.
AB  - Intracellular calcium dynamics are critical to cellular functions like pain
      transmission. Extracellular ATP plays an important role in modulating
      intracellular calcium levels by interacting with the P2 family of surface
      receptors. In this study, we developed a mechanistic mathematical model of ATP
      induced P2 mediated calcium signaling in archetype sensory neurons. The model
      architecture, which described 90 species connected by 162 interactions, was
      formulated by aggregating disparate molecular modules from literature. Unlike
      previous models, only mass action kinetics were used to describe the rate of
      molecular interactions. Thus, the majority of the 252 unknown model parameters
      were either association, dissociation or catalytic rate constants. Model
      parameters were estimated from nine independent data sets taken from multiple
      laboratories. The training data consisted of both dynamic and steady-state
      measurements. However, because of the complexity of the calcium network, we were
      unable to estimate unique model parameters. Instead, we estimated a family or
      ensemble of probable parameter sets using a multi-objective thermal ensemble
      method. Each member of the ensemble met an error criterion and was located along
      or near the optimal trade-off surface between the individual training data sets.
      The model quantitatively reproduced experimental measurements from dorsal root
      ganglion neurons as a function of extracellular ATP forcing. Hypothesized
      architecture linking phosphoinositide regulation with P2X receptor activity
      explained the inhibition of P2X-mediated current flow by activated metabotropic
      P2Y receptors. Sensitivity analysis using individual and the whole system outputs
      suggested which molecular subsystems were most important following P2 activation.
      Taken together, modeling and analysis of ATP-induced P2 mediated calcium
      signaling generated qualitative insight into the critical interactions
      controlling ATP induced calcium dynamics. Understanding these critical
      interactions may prove useful for the design of the next generation of molecular
      pain management strategies.

PMID- 19750221
TI  - Epitope mapping of HIV-specific CD8+ T cells in a cohort dominated by clade A1
      infection.
AB  - BACKGROUND: CD8+ T cell responses are often detected at large magnitudes in HIV
      infected subjects, and eliciting these responses is the central aim of many HIV-1
      vaccine strategies. Population differences in CD8+ T cell epitope specificity
      will need to be understood if vaccines are to be effective in multiple geographic
      regions. METHODOLOGY/PRINCIPAL FINDINGS: In a large Kenyan cohort, we compared
      responsive CD8+ T cell HIV-1 Env overlapping peptides (OLPs) to Best Defined
      Epitopes (BDEs), many of which have been defined in clade B infection. While the
      majority of BDEs (69%) were recognized in this population, nearly half of
      responsive OLPs (47%) did not contain described epitopes. Recognition frequencies
      of BDEs were inversely correlated to epitopic sequence differences between clade
      A1 and BDE (P = 0.019), and positively selected residues were more frequent in
      "new" OLPs (without BDEs). We assessed the impact of HLA and TAP binding on
      epitope recognition frequencies, focusing on predicted and actual epitopes in the
      HLA B7 supertype. CONCLUSIONS/SIGNIFICANCE: Although many previously described
      CD8 epitopes were recognized, several novel CD8 epitopes were defined in this
      population, implying that epitope mapping efforts have not been completely
      exhausted. Expansion of these studies will be critical to understand population
      differences in CD8 epitope recognition.

PMID- 19750222
TI  - Adult type 3 adenylyl cyclase-deficient mice are obese.
AB  - BACKGROUND: A recent study of obesity in Swedish men found that polymorphisms in
      the type 3 adenylyl cyclase (AC3) are associated with obesity, suggesting the
      interesting possibility that AC3 may play a role in weight control. Therefore, we
      examined the weight of AC3 mice over an extended period of time.
      METHODOLOGY/PRINCIPAL FINDINGS: We discovered that AC3(-/-) mice become obese as
      they age. Adult male AC3(-/-) mice are about 40% heavier than wild type male mice
      while female AC3(-/-) are 70% heavier. The additional weight of AC3(-/-) mice is
      due to increased fat mass and larger adipocytes. Before the onset of obesity,
      young AC3(-/-) mice exhibit reduced physical activity, increased food
      consumption, and leptin insensitivity. Surprisingly, the obesity of AC3(-/-) mice
      is not due to a loss of AC3 from white adipose and a decrease in lipolysis.
      CONCLUSIONS/SIGNIFICANCE: We conclude that mice lacking AC3 exhibit obesity that
      is apparently caused by low locomotor activity, hyperphagia, and leptin
      insensitivity. The presence of AC3 in primary cilia of neurons of the
      hypothalamus suggests that cAMP signals generated by AC3 in the hypothalamus may
      play a critical role in regulation of body weight.

PMID- 19750223
TI  - Shiga toxin and lipopolysaccharide induce platelet-leukocyte aggregates and
      tissue factor release, a thrombotic mechanism in hemolytic uremic syndrome.
AB  - BACKGROUND: Aggregates formed between leukocytes and platelets in the circulation
      lead to release of tissue factor (TF)-bearing microparticles contributing to a
      prothrombotic state. As enterohemorrhagic Escherichia coli (EHEC) may cause
      hemolytic uremic syndrome (HUS), in which microthrombi cause tissue damage, this
      study investigated whether the interaction between blood cells and EHEC virulence
      factors Shiga toxin (Stx) and lipopolysaccharide (LPS) led to release of TF.
      METHODOLOGY/PRINCIPAL FINDINGS: The interaction between Stx or LPS and blood
      cells induced platelet-leukocyte aggregate formation and tissue factor (TF)
      release, as detected by flow cytometry in whole blood. O157LPS was more potent
      than other LPS serotypes. Aggregates formed mainly between monocytes and
      platelets and less so between neutrophils and platelets. Stimulated blood cells
      in complex expressed activation markers, and microparticles were released.
      Microparticles originated mainly from platelets and monocytes and expressed TF.
      TF-expressing microparticles, and functional TF in plasma, increased when blood
      cells were simultaneously exposed to the EHEC virulence factors and high shear
      stress. Stx and LPS in combination had a more pronounced effect on platelet
      monocyte aggregate formation, and TF expression on these aggregates, than each
      virulence factor alone. Whole blood and plasma from HUS patients (n = 4) were
      analyzed. All patients had an increase in leukocyte-platelet aggregates, mainly
      between monocytes and platelets, on which TF was expressed during the acute phase
      of disease. Patients also exhibited an increase in microparticles, mainly
      originating from platelets and monocytes, bearing surface-bound TF, and
      functional TF was detected in their plasma. Blood cell aggregates,
      microparticles, and TF decreased upon recovery. CONCLUSIONS/SIGNIFICANCE: By
      triggering TF release in the circulation, Stx and LPS can induce a prothrombotic
      state contributing to the pathogenesis of HUS.

PMID- 19750224
TI  - Autophagy gene variant IRGM -261T contributes to protection from tuberculosis
      caused by Mycobacterium tuberculosis but not by M. africanum strains.
AB  - The human immunity-related GTPase M (IRGM) has been shown to be critically
      involved in regulating autophagy as a means of disposing cytosolic cellular
      structures and of reducing the growth of intracellular pathogens in vitro. This
      includes Mycobacterium tuberculosis, which is in agreement with findings
      indicating that M. tuberculosis translocates from the phagolysosome into the
      cytosol of infected cells, where it becomes exposed to autophagy. To test whether
      IRGM plays a role in human infection, we studied IRGM gene variants in 2010
      patients with pulmonary tuberculosis (TB) and 2346 unaffected controls.
      Mycobacterial clades were classified by spoligotyping, IS6110 fingerprinting and
      genotyping of the pks1/15 deletion. The IRGM genotype -261TT was negatively
      associated with TB caused by M. tuberculosis (OR 0.66, CI 0.52-0.84, P(nominal)
      0.0009, P(corrected) 0.0045) and not with TB caused by M. africanum or M. bovis
      (OR 0.95, CI 0.70-1.30. P 0.8). Further stratification for mycobacterial clades
      revealed that the protective effect applied only to M. tuberculosis strains with
      a damaged pks1/15 gene which is characteristic for the Euro-American (EUAM)
      subgroup of M. tuberculosis (OR 0.63, CI 0.49-0.81, P(nominal) 0.0004,
      P(corrected) 0.0019). Our results, including those of luciferase reporter gene
      assays with the IRGM variants -261C and -261T, suggest a role for IRGM and
      autophagy in protection of humans against natural infection with M. tuberculosis
      EUAM clades. Moreover, they support in vitro findings indicating that TB lineages
      capable of producing a distinct mycobacterial phenolic glycolipid that occurs
      exclusively in strains with an intact pks1/15 gene inhibit innate immune
      responses in which IRGM contributes to the control of autophagy. Finally, they
      raise the possibility that the increased frequency of the IRGM -261TT genotype
      may have contributed to the establishment of M. africanum as a pathogen in the
      West African population.

PMID- 19750225
TI  - Financing of U.S. biomedical research and new drug approvals across therapeutic
      areas.
AB  - BACKGROUND: We estimated U.S. biomedical research funding across therapeutic
      areas, determined the association with disease burden, and evaluated new drug
      approvals that resulted from this investment. METHODOLOGY/PRINCIPAL FINDINGS: We
      calculated funding from 1995 to 2005 and totaled Food and Drug Administration
      approvals in eight therapeutic areas (cardiovascular, endocrine,
      gastrointestinal, genitourinary, HIV/AIDS, infectious disease excluding HIV,
      oncology, and respiratory) primarily using public data. We then calculated
      correlations between funding, published estimates of disease burden, and drug
      approvals. Financial support for biomedical research from 1995 to 2005 increased
      across all therapeutic areas between 43% and 369%. Industry was the principal
      funder of all areas except HIV/AIDS, infectious disease, and oncology, which were
      chiefly sponsored by the National Institutes of Health (NIH). Total (rho = 0.70;
      P = .03) and industry funding (rho = 0.69; P = .04) were correlated with
      projected disease burden in high income countries while NIH support (rho = 0.80;
      P = .01) was correlated with projected disease burden globally. From 1995 to 2005
      the number of new approvals was flat or declined across therapeutic areas, and
      over an 8-year lag period, neither total nor industry funding was correlated with
      future approvals. CONCLUSIONS/SIGNIFICANCE: Across therapeutic areas, biomedical
      research funding increased substantially, appears aligned with disease burden in
      high income countries, but is not linked to new drug approvals. The translational
      gap between funding and new therapies is affecting all of medicine, and remedies
      must include changes beyond additional financial investment.

PMID- 19750226
TI  - Selective deletion of PTEN in dopamine neurons leads to trophic effects and
      adaptation of striatal medium spiny projecting neurons.
AB  - The widespread distribution of the tumor suppressor PTEN in the nervous system
      suggests a role in a broad range of brain functions. PTEN negatively regulates
      the signaling pathways initiated by protein kinase B (Akt) thereby regulating
      signals for growth, proliferation and cell survival. Pten deletion in the mouse
      brain has revealed its role in controlling cell size and number. In this study,
      we used Cre-loxP technology to specifically inactivate Pten in dopamine (DA)
      neurons (Pten KO mice). The resulting mutant mice showed neuronal hypertrophy,
      and an increased number of dopaminergic neurons and fibers in the ventral
      mesencephalon. Interestingly, quantitative microdialysis studies in Pten KO mice
      revealed no alterations in basal DA extracellular levels or evoked DA release in
      the dorsal striatum, despite a significant increase in total DA tissue levels.
      Striatal dopamine receptor D1 (DRD1) and prodynorphin (PDyn) mRNA levels were
      significantly elevated in KO animals, suggesting an enhancement in neuronal
      activity associated with the striatonigral projection pathway, while dopamine
      receptor D2 (DRD2) and preproenkephalin (PPE) mRNA levels remained unchanged. In
      addition, PTEN inactivation protected DA neurons and significantly enhanced DA
      dependent behavioral functions in KO mice after a progressive 6OHDA lesion. These
      results provide further evidence about the role of PTEN in the brain and suggest
      that manipulation of the PTEN/Akt signaling pathway during development may alter
      the basal state of dopaminergic neurotransmission and could provide a therapeutic
      strategy for the treatment of Parkinson's disease, and other neurodegenerative
      disorders.

PMID- 19750227
TI  - Spatio-temporal dynamics of human intention understanding in temporo-parietal
      cortex: a combined EEG/fMRI repetition suppression paradigm.
AB  - Inferring the intentions of other people from their actions recruits an inferior
      fronto-parietal action observation network as well as a putative social network
      that includes the posterior superior temporal sulcus (STS). However, the
      functional dynamics within and among these networks remains unclear. Here we used
      functional magnetic resonance imaging (fMRI) and high-density
      electroencephalogram (EEG), with a repetition suppression design, to assess the
      spatio-temporal dynamics of decoding intentions. Suppression of fMRI activity to
      the repetition of the same intention was observed in inferior frontal lobe,
      anterior intraparietal sulcus (aIPS), and right STS. EEG global field power was
      reduced with repeated intentions at an early (starting at 60 ms) and a later
      (approximately 330 ms) period after the onset of a hand-on-object encounter.
      Source localization during these two intervals involved right STS and aIPS
      regions highly consistent with RS effects observed with fMRI. These results
      reveal the dynamic involvement of temporal and parietal networks at multiple
      stages during the intention decoding and without a strict segregation of
      intention decoding between these networks.

PMID- 19750228
TI  - Chronic cyclodextrin treatment of murine Niemann-Pick C disease ameliorates
      neuronal cholesterol and glycosphingolipid storage and disease progression.
AB  - BACKGROUND: Niemann-Pick type C (NPC) disease is a fatal neurodegenerative
      disorder caused most commonly by a defect in the NPC1 protein and characterized
      by widespread intracellular accumulation of unesterified cholesterol and
      glycosphingolipids (GSLs). While current treatment therapies are limited, a few
      drugs tested in Npc1(-/-) mice have shown partial benefit. During a combination
      treatment trial using two such compounds, N-butyldeoxynojirimycin (NB-DNJ) and
      allopregnanolone, we noted increased lifespan for Npc1(-/-) mice receiving only 2
      hydroxypropyl-beta-cyclodextrin (CD), the vehicle for allopregnanolone. This
      finding suggested that administration of CD alone, but with greater frequency,
      might provide additional benefit. METHODOLOGY/PRINCIPAL FINDINGS: Administration
      of CD to Npc1(-/-) mice beginning at either P7 or P21 and continuing every other
      day delayed clinical onset, reduced intraneuronal cholesterol and GSL storage as
      well as free sphingosine accumulation, reduced markers of neurodegeneration, and
      led to longer survival than any previous treatment regime. We reasoned that other
      lysosomal diseases characterized by cholesterol and GSL accumulation, including
      NPC disease due to NPC2 deficiency, GM1 gangliosidosis and mucopolysaccharidosis
      (MPS) type IIIA, might likewise benefit from CD treatment. Treated Npc2(-/-) mice
      showed benefits similar to NPC1 disease, however, mice with GM1 gangliosidosis or
      MPS IIIA failed to show reduction in storage. CONCLUSIONS/SIGNIFICANCE: Treatment
      with CD delayed clinical disease onset, reduced intraneuronal storage and
      secondary markers of neurodegeneration, and significantly increased lifespan of
      both Npc1(-/-) and Npc2(-/-) mice. In contrast, CD failed to ameliorate
      cholesterol or glycosphingolipid storage in GM1 gangliosidosis and MPS IIIA
      disease. Understanding the mechanism(s) by which CD leads to reduced neuronal
      storage may provide important new opportunities for treatment of NPC and related
      neurodegenerative diseases characterized by cholesterol dyshomeostasis.

PMID- 19750229
TI  - A comprehensive microarray-based DNA methylation study of 367 hematological
      neoplasms.
AB  - BACKGROUND: Alterations in the DNA methylation pattern are a hallmark of
      leukemias and lymphomas. However, most epigenetic studies in hematologic
      neoplasms (HNs) have focused either on the analysis of few candidate genes or
      many genes and few HN entities, and comprehensive studies are required.
      METHODOLOGY/PRINCIPAL FINDINGS: Here, we report for the first time a microarray
      based DNA methylation study of 767 genes in 367 HNs diagnosed with 16 of the most
      representative B-cell (n = 203), T-cell (n = 30), and myeloid (n = 134)
      neoplasias, as well as 37 samples from different cell types of the hematopoietic
      system. Using appropriate controls of B-, T-, or myeloid cellular origin, we
      identified a total of 220 genes hypermethylated in at least one HN entity. In
      general, promoter hypermethylation was more frequent in lymphoid malignancies
      than in myeloid malignancies, being germinal center mature B-cell lymphomas as
      well as B and T precursor lymphoid neoplasias those entities with highest
      frequency of gene-associated DNA hypermethylation. We also observed a significant
      correlation between the number of hypermethylated and hypomethylated genes in
      several mature B-cell neoplasias, but not in precursor B- and T-cell leukemias.
      Most of the genes becoming hypermethylated contained promoters with high CpG
      content, and a significant fraction of them are targets of the polycomb repressor
      complex. Interestingly, T-cell prolymphocytic leukemias show low levels of DNA
      hypermethylation and a comparatively large number of hypomethylated genes, many
      of them showing an increased gene expression. CONCLUSIONS/SIGNIFICANCE: We have
      characterized the DNA methylation profile of a wide range of different HNs
      entities. As well as identifying genes showing aberrant DNA methylation in
      certain HN subtypes, we also detected six genes--DBC1, DIO3, FZD9, HS3ST2, MOS,
      and MYOD1--that were significantly hypermethylated in B-cell, T-cell, and myeloid
      malignancies. These might therefore play an important role in the development of
      different HNs.

PMID- 19750230
TI  - Distinct high-profile methylated genes in colorectal cancer.
AB  - BACKGROUND: Mutations and promoters' methylation of a set of candidate cancer
      genes (CAN genes) are associated with progression of colorectal cancer (CRC). We
      hypothesized that these genes' promoters are inactivated through epigenetic
      silencing and may show a different profile in high-risk populations. We
      investigated the status of CAN gene methylation and CHD5 protein expression in
      African American CRC tissue microarrays (TMA) using immunohistochemical staining.
      METHODOLOGY/PRINCIPAL FINDINGS: The promoter methylation status of the CAN genes
      was studied by methylation-specific PCR (MSP) in 51 Iranians (a white population)
      and 51 African Americans (AA). Microsatellite instability (MSI) was analyzed as
      well. The differential frequency of methylation for each gene was tested by chi
      square analysis between the two groups based on matched age and sex. CHD5 protein
      expression was evaluated in moderate to well differentiated and poorly
      differentiated carcinomas compared to matched normal tissue using TMA. In
      addition, the correlation between these epigenetic biomarkers and various
      clinicopathological factors, including, age, location, and stage of the disease
      were analyzed. Seventy-seven and 34% of tumors were distal in Iranian and African
      American patients, respectively. In both populations, the percentage of
      methylation was >65% for SYNE1, MMP2, APC2, GPNMB, EVL, PTPRD, and STARD8,
      whereas methylation was <50% for LGR6, RET, CD109, and RNF. The difference in
      methylation between the two populations was statistically significant for CHD5,
      ICAM5 and GPNMB. Thirty-one percent AA tumors showed MSI-H, compared to 28% in
      Iranians. CONCLUSIONS/SIGNIFICANCE: A significantly higher methylation rate was
      found for GPNMB, ICAM5, and CHD5 genes in AA patients compared to Iranians. These
      genes might play a role in the high incidence and aggressiveness of CRC in the AA
      population. The hypermethylation of the CAN genes can be considered as a marker
      of colon carcinogenesis.

PMID- 19750231
TI  - Management of osteoporosis in the aging male: focus on zoledronic acid.
AB  - Osteoporosis in the aging male remains an important yet under-recognized and
      undertreated disease. Current US estimates indicate that over 14 million men have
      osteoporosis or low bone mass, and men suffer approximately 500,000 osteoporotic
      fractures each year. Men experience fewer osteoporotic fractures than women but
      have higher mortality after fracture. Bisphosphonates are potent antiresorptive
      agents that inhibit osteoclast activity, suppress in vivo markers of bone
      turnover, increase bone mineral density, decrease fractures, and improve survival
      in men with osteoporosis. Intravenous zoledronic acid may be a preferable
      alternative to oral bisphosphonate therapy in patients with cognitive
      dysfunction, the inability to sit upright, or significant gastrointestinal
      pathology. Zoledronic acid (Reclast) is approved in the US as an annual 5 mg
      intravenous infusion to treat osteoporosis in men. The zoledronic acid (Zometa) 4
      mg intravenous dose has been studied in the prevention of bone loss associated
      with androgen deprivation therapy.

PMID- 19750232
TI  - Restless legs syndrome: differential diagnosis and management with pramipexole.
AB  - Restless legs syndrome (RLS) is a condition characterized by discomfort at rest
      and urge to move focused on the legs. RLS may occur as an idiopathic, often
      hereditary condition (primary RLS), or in association with medical conditions
      (secondary RLS) including iron deficiency, uremia, and polyneuropathy. Current
      understanding of the pathophysiology of RLS points to the involvement of three
      interrelated components: dopaminergic dysfunction, impaired iron homeostasis, and
      genetic mechanisms. The diagnosis of RLS is made according to the consensus
      criteria by a National Institutes of Health panel: 1) an urge to move the legs,
      usually accompanied by uncomfortable sensations; 2) beginning or worsening during
      rest; 3) relieved by movement; and 4) worse, or only occurring, in the evening or
      at night. The differential diagnosis of RLS aims to: 1) distinguish RLS from
      other disorders with RLS-like symptoms and 2) identify secondary forms, with
      investigation of underlying diseases. The treatment of RLS demands a clinical
      evaluation to rule out and cure causes of secondary RLS, including iron
      supplementation when deficient, and to eliminate the triggering factors. The
      presence of neuropathy should be especially investigated in nonhereditary, late
      onset RLS, in view of a possible treatment of the underlying disease. The first
      line treatment for idiopathic RLS is represented by dopamine agonists, in
      particular nonergot-derived ropinirole and pramipexole, whereas ergot dopamine
      agonists (cabergoline and pergolide) are no longer in first-line use given the
      risks of cardiac valvulopathy. Although no comparative trials have been
      published, a meta-analysis of pramipexole versus ropinirole suggests differences
      in efficacy and tolerability favoring pramipexole.

PMID- 19750233
TI  - A case of polypoidal choroidal vasculopathy. Periphery is equally important for
      such patients.
AB  - BACKGROUND: To report a case of peripheral polypoidal choroidal vasculopathy
      (PCV) which was treated successfully. METHODS: Interventional case report. Best
      corrected visual acuity measurements (BCVA), slit-lamp examination, fundus
      biomicroscopy, fluorescein angiography (FFA), and indocyanine green angiography
      (ICGA) were performed at baseline examination and during the follow-up period.
      The patient underwent ICGA-guided argon laser to treat the active polyps.
      RESULTS: An 82-year-old Caucasian man presented complaining of sudden
      deterioration of peripheral vision in his left eye (LE). His previous ocular
      history was associated with advanced age-related macular degeneration (AMD)
      involving both eyes (BE). Fundus examination revealed macular scars in BE and a
      large hemorrhagic pigment epithelial detachment (PED) temporal to the macula in
      the LE. ICGA revealed active polyps at the margins of the PED. The patient
      underwent ICGA-guided argon laser to treat the active polyps. Six months post
      laser, the patient regained his peripheral vision with resolution of the
      hemorrhagic PED and remains stable until now, one year after treatment.
      CONCLUSIONS: Appropriate treatment and regular follow-up is important in patients
      with PCV and peripheral lesions even if central vision is lost.

PMID- 19750234
TI  - Potential prescription patterns and errors in elderly adult patients attending
      public primary health care centers in Mexico City.
AB  - INTRODUCTION: Six out of every 10 elderly persons live in developing countries.
      OBJECTIVE: To analyze and assess the drug prescription patterns and errors in
      elderly outpatients attending public health care centers in Mexico City, Mexico.
      MATERIALS AND METHODS: A descriptive and retrospective study was conducted in
      2007. Fourteen hundred prescriptions were analyzed. Prescriptions of ambulatory
      adults aged >70 years who were residents of Mexico City for at least two years
      were included. Prescription errors were divided into two groups: (1)
      administrative and legal, and (2) pharmacotherapeutic. In group 2, we analyzed
      drug dose strength, administration route, frequency of drug administration,
      treatment length, potential drug-drug interactions, and contraindications.
      Variables were classified as correct or incorrect based on clinical literature.
      Variables for each drug were dichotomized as correct (0) or incorrect (1). A
      Prescription Index (PI) was calculated by considering each drug on the
      prescription. SPSS statistical software was used to process the collected data
      (95% confidence interval; p <0.05). RESULTS: The drug prescription pattern in
      elderly outpatients shows that 12 drugs account for 70.72% (2880) of prescribed
      drugs. The most prescribed drugs presented potential pharmacotherapeutic errors
      (as defined in the present study). Acetylsalicylic acid-captopril was the most
      common potential interaction (not clinically assessed). Potential prescription
      error was high (53% of total prescriptions). Most of the prescription errors were
      due to omissions of dosage, administration route, and length of treatment and may
      potentially cause harm to the elderly outpatients. CONCLUSIONS: A high number of
      potential prescription errors were found, mainly due to omissions. The drug
      prescription pattern of the study population is mainly constituted by 12 drugs.
      The results indicate that prescription quality depends on the number of
      prescribed drugs per prescription (p < 0.000).

PMID- 19750235
TI  - Efficacy and safety of risperidone long-acting injection in elderly people with
      schizophrenia.
AB  - Antipsychotic medication is the mainstay of treatment in elderly patients with
      psychosis. In recent years, second generation antipsychotics have come to be
      preferred. Long-acting risperidone is the first such antipsychotic available for
      use in this vulnerable group of patients and offers an attractive alternative to
      traditional medications. The available literature revealed that long-acting
      risperidone is generally well tolerated and is effective in treating both the
      positive and negative symptoms of schizophrenia. Despite a lack of randomized
      trials and head-to-head studies, it appears to be a useful addition to the
      treatment armory for patients with chronic psychosis who require a depot
      preparation. Further research into its endocrine and metabolic side effects is
      needed.

PMID- 19750236
TI  - Molecular cloning, characterization, and expression analysis of the CXCR4 gene
      from Turbot: Scophthalmus maximus.
AB  - Chemokine receptor 4 (CXCR4) belongs to the large superfamily of G protein
      coupled receptors. The EST sequence of CXCR4 from turbot (Scophthalmus maximus
      L.) was obtained from a subtractive cDNA library. In the present study, the full
      length cDNA sequence of turbot CXCR4 was obtained, and sequence analysis
      indicated that its primary structure was highly similar to CXCR4 from other
      vertebrates. Quantitative real-time PCR demonstrated that the highest expression
      level of turbot CXCR4 was in the spleen following injection with physiological
      saline (PS). After turbot were challenged with Vibrio harveyi, the lowest
      expression level of CXCR4 was detected at 8 hours in the spleen and 12 hours in
      the head kidney, and then increased gradually to 36 hours. These findings
      suggested that CXCR4 may play a significant role in the immune response of
      turbot.

PMID- 19750237
TI  - The prognostic significance of the preoperative full blood count after resection
      of colorectal liver metastases.
AB  - INTRODUCTION: Increased preoperative platelet and neutrophil counts are risk
      factors for decreased survival in several different malignancies. Our aim was to
      investigate the relationship between overall or disease-free survival after
      resection of CRLM and the preoperative haematological parameters. METHODS: We
      reviewed a cohort of 140 patients who underwent resection of CRLM with curative
      intent, utilising prospectively maintained databases. Patient demographics,
      operative details, FBC, CRP, INR, histopathology results, and survival data were
      examined. Kaplan-Meier survival and Cox regression analyses were used to
      determine the impact of all variables on survival. RESULTS: 140 patients (96
      males) with a median age of 67 years (range 33-82 years) underwent resection of
      CRLM. A significant correlation was exhibited between preoperative platelet count
      and neutrophil count (rho = 0.186, P = .028). When modelled as continuous
      covariates in a Cox regression hazards, an increased preoperative platelet (P =
      .02) and neutrophil counts (P <or= .001) were significantly associated with
      overall survival. Of the haematological parameters assessed only preoperative
      platelet count showed a strong trend of association with disease free survival;
      however this failed to reach statistical significance (P = .076). CONCLUSIONS:
      Increased preoperative platelet and neutrophil counts are independent risk
      factors for decreased survival in patients undergoing resection of CRLM in our
      series of patients. These findings require validation in larger studies to
      determine their relationship with survival. Further research into the role of
      these cell types in tumour progression, particularly in the development and
      inhibition of angiogenesis, is warranted.

PMID- 19750238
TI  - Herpes simplex esophagitis in immunocompetent host: a case report.
AB  - Introduction. Herpes simplex esophagitis is well recognized in immunosuppressed
      subjects, but it is infrequent in immunocompetent patients. We present a case of
      HSE in a 53-year-old healthy man. Materials and Methods. The patient was admitted
      with dysphagia, odynophagia, and retrosternal chest pain. An
      esophagogastroduodenoscopy revealed minute erosive area in distal esophagus and
      biopsies confirmed esophagitis and findings characteristic of Herpes Simplex
      Virus infection. Results. The patients was treated with high dose of protonpump
      inhibitor, sucralfate, and acyclovir, orally, with rapid resolution of symptoms.
      Discussion. HSV type I is the second most common cause of infectious esophagitis.
      The majority of symptomatic immunocompetent patients with HSE will present with
      an acute onset of esophagitis. Endoscopic biopsies from the ulcer edges should be
      obtained for both histopathology and viral culture. In immunocompetent host, HSE
      is generally a self-limited condition. Conclusions. HSE should be suspected in
      case of esophagitis without evident cause, even if the patient is
      immunocompetent. When the diagnosis of HSE is confirmed, careful history and
      assessment for an immune disorder such as HIV infection is crucial, to look for
      underlying immune deficiency.

PMID- 19750239
TI  - Cognitive Plasticity and Cortical Modules.
AB  - Some organisms learn to calculate, accumulate knowledge, and communicate in ways
      that others do not. What factors determine which intellectual abilities a
      particular species or individual can easily acquire? I propose that cognitive
      skill learning capacity reflects (a) the availability of specialized cortical
      circuits, (b) the flexibility with which cortical activity is coordinated, and
      (c) the customizability of cortical networks. This framework can potentially
      account for differences in learning capacity across species, individuals, and
      developmental stages. Understanding the mechanisms that constrain cognitive
      plasticity is fundamental to developing new technologies and educational
      practices that maximize intellectual advancements.

PMID- 19750240
TI  - Cryo-banking of Prunus mume pollen and its application in cross-breeding.
AB  - The Mei (Prunus mume Sieb. et Zucc.) is one of the most widely used landscape
      plants and important germplasm resources in China. The study of pollen
      cryopreservation and the construction of a pollen cryo-bank have great importance
      in Mei research. From 2003 to 2007 we cryopreserved pollen from 51 Mei cultivars.
      In vitro germination of cryopreserved pollen was not significantly different from
      that of fresh pollen, even after four years of storage in liquid nitrogen.
      Cryopreserved pollen of 19 cultivars was used successfully for intraspecific
      hybridizations at Wuhan and Beijing in 2005 and 2006.

PMID- 19750241
TI  - Improved recovery of cryotherapy-treated shoot tips following thermotherapy of in
      vitro-grown stock shoots of raspberry (Rubus idaeus L.).
AB  - Raspberry bushy dwarf virus (RBDV) can be efficiently eradicated from raspberry
      plants (Rubus idaeus) by a procedure combining thermotherapy and cryotherapy.
      However, the bottleneck of this procedure is that, following thermotherapy,
      cryopreserved shoot tips become chlorotic during regrowth and eventually die
      after several subcultures. In addition, survival of heat-treated stock shoots and
      recovery of cryopreserved shoot tips following thermotherapy are low. The present
      study focused towards improving regrowth of cryopreserved raspberry shoot tips
      following thermotherapy. Results showed that preconditioning stock shoots with
      salicylic acid (SA; 0.01-0.1 mM) markedly increased survival of stock shoots
      after 4 weeks of thermotherapy. Regrowth of cryopreserved shoot tips following
      thermotherapy was also significantly enhanced when SA (0.05-0.1 mM) was used for
      preconditioning stock shoots. Addition of either Fe-ethylenediaminetetracetic
      acid (Fe-EDTA, 50 mg per L) or Fe-ethylenediaminedi(o)hydroxyphenylacetic acid
      (Fe-EDDHA, 50 mg per L) to post-culture medium strongly promoted regrowth and
      totally prevented chlorosis of shoots regenerated from cryopreserved shoot tips
      following thermotherapy. Using the parameters optimized in the present study,
      about 80 percent survival of heat-treated stock shoots and about 33 percent
      regrowth of cryopreserved shoot tips following thermotherapy were obtained.
      Morphology of plants regenerated from cryopreserved shoot tips following
      thermotherapy was identical to that of control plants, based on observations of
      leaf shape and size, internode length and plant height. Optimization of the
      thermotherapy procedure followed by cryotherapy will facilitate the wider
      application of this technique to eliminate viruses which can invade meristems.

PMID- 19750242
TI  - Limbal explants from cryopreserved cadaver human corneas. Immunofluorescence and
      light microscopy of epithelial cells growing in culture.
AB  - The aim of the present study was to determine whether human cadaver corneas, that
      were subject to cryopreservation, would be a source of migrating epithelial cells
      in vitro and what kind of morphological features these cells possess. Limbal
      explant culture was used for expanding the epithelial cells. Non-quantitative
      light microscopical examinations of the cultures within a period of 28 days were
      carried out. The phenotype of cultured cells, particularly of the presumed adult
      stem cell population, was examined by indirect fluorescent immunostaining using
      antibodies against corneal stem cell associated markers p63 and vimentin. The
      effectiveness of the freezing-thawing protocol was confirmed by cultivation of
      limbal explants taken from non-cryopreserved cadaver corneoscleral rims. The
      result clearly showed that limbal tissue, subjected to cryopreservation and long
      lasting (up to 12 months) storage in liquid nitrogen, retains the capacity to be
      source of migrating and proliferating epithelial cells in vitro including the
      presumed adult stem cells and transient amplifying cells.

PMID- 19750243
TI  - Cryopreservation of canine ovarian and testicular fibroblasts.
AB  - To derive a practical procedure to store canine somatic cells, fibroblasts
      isolated from testicular or ovarian tissues were cryopreserved in 1.2 M ethylene
      glycol or in 1.2 M dimethylsulfoxide prepared in Dulbecco's Modified Eagle Medium
      as cryoprotectants, and were frozen either in plastic straws or vials. Thawed
      cells were cultured for 24 hr at 38.5 degree C in a humidified atmosphere of 5
      percent CO2 95 percent air, and then their membrane integrity was assayed with a
      double fluorescent stain, Fertilight. In addition, frozen-thawed fibroblasts were
      cultured for 4 days, and then their functional survival was measured after
      staining small colonies with trypan blue. After freezing and thawing, membrane
      integrity of testicular fibroblasts was 55-70 percent and functional survival
      ranged from 20-40 percent. With frozen-thawed ovarian cells, the average membrane
      integrity was 55-75 percent and the average functional survival was 35-40
      percent. When frozen in ethylene glycol, functional survival of ovarian
      fibroblasts was significantly higher than that of testicular cells (P less than
      0.05). These methods should prove useful to preserve cells collected from canids
      in the wild.

PMID- 19750244
TI  - Effects of sucrose preculture on cryopreservation by droplet-vitrification of
      strawberry cultivars and morphological stability of cryopreserved plants.
AB  - The droplet-vitrification method was applied to shoot tips of micropropagated
      strawberry plants (Fragaria x ananassa DUCH. cvs. 'Senga Sengana', 'Korona' and
      'Aroma'). Shoot tips of 2 - 3 mm in length were precultured in sucrose (0.1,
      0.25, 0.5, 0.75, 1.0 M) enriched media for 24 and 48 h. Subsequently, they were
      transferred into 6 microl droplets of PVS2 vitrification solution for 20 min and
      plunged into liquid nitrogen. Rapid rewarming was done in liquid medium at room
      temperature. The highest recovery rate in all cultivars (60 percent) was achieved
      after a preculture with 0.25 M sucrose for 24 h. From the recovered shoot tips
      not all continued with shoot development and multiplication. The number of off
      types observed in the field was affected by the sucrose concentration. After
      preculture in 0.1 M sucrose no off-types were observed, while after preculture in
      high sucrose concentrations the number of off-types was much higher reaching 20
      percent at the highest sucrose concentration.

PMID- 19750245
TI  - Sucrose treatment and explant water content: critical factors to consider in
      development of successful cryopreservation protocols for shoot tip explants of
      the tropical species Dioscorea rotundata (YAM).
AB  - A study was conducted to determine the optimum methods for conditioning explants
      to be used in the development of a simple protocol for long-term conservation of
      the germplasm of Dioscorea rotundata via cryopreservation. Shoot tips from
      cultures maintained in vitro were exposed to high concentrations of sucrose prior
      to silica gel-based dehydration and vitrification solution-based cryopreservation
      protocols. Explant water contents were determined, and ultrastructural studies
      were also carried out. Initially, culturing explants on medium supplemented with
      0.3 M sucrose for 3-5 d considerably reduced tissue water content from about 12.2
      g/g dry mass to between 4.8 and 5.5 g/g dry mass before cryoprotection with
      modified PVS2 (MPVS2) or silica gel dehydration. Ultrastructural studies
      indicated that cells had deposits of starch in plastids following sucrose
      treatments. Survival for D. rotundata shoot tips treated with MPVS2 vitrification
      solution, unloaded with 1.0 M sucrose medium and cooled to -7 degree C, was 16
      percent for 15 min treatment and 44 percent for 40 min. After the 40 min MPVS2
      treatment the TTZ test indicated 88 percent viability retention of explants
      cooled to -70 degree C, and 44 percent at -196 degree C. Plantlet development was
      obtained for -70 degree C-cooled shoot tips, whereas only callus development
      occurred from tissues exposed to liquid nitrogen. Explant regeneration was not
      obtained with air-dehydration techniques. It was concluded that vitrification
      solution based cryopreservation presently offers the best option for conservation
      of this Dioscorea species.

PMID- 19750246
TI  - Cryopreservation of marine diatom algae by encapsulation-vitrification.
AB  - In this paper, the cryopreservation of marine diatom algae (Nitzschia closterium
      f. minutissima Allen and Nelson and Chaetoceros muelleri Lemmermann) using the
      encapsulation-vitrification technique was studied. The effect of the composition
      the vitrification solution, of the concentration of the loading solution, of the
      duration of loading and dehydration treatments and of the washing method on
      viability of algae was investigated. The results showed that PVS2 was suitable
      for cryopreservation of these diatoms. In the case of N. closterium, the highest
      viability (73.8 percent) was obtained when alginate beads containing the algal
      cells were loaded with 50 percent PVS2 for 60 min, dehydrated with 100 percent
      PVS2 for 60 min at 0 degree C, frozen and rewarmed rapidly and washed with a 1.2
      M sucrose solution for 30 min at 20 degree C. In the case of C. muelleri, the
      highest viability (48.2 percent) was obtained when alginate beads containing the
      algal cells were loaded with 50 percent PVS2 for 40 min, dehydrated with 100
      percent PVS2 for 60 min at 0 degree C, frozen and rewarmed rapidly and washed
      with a 1.2 M sucrose solution for 30 min at 20 degree C.

PMID- 19750248
TI  - A southern alliance for research and innovation in mental health.

PMID- 19750247
TI  - Cryopreservation of Ginkgo biloba cell culture: effect of pretreatment with
      sucrose and ABA.
AB  - The report describes the impact of preculture with sucrose and sucrose + ABA on
      desiccation and cryopreservation tolerance of cell cultures of Ginkgo biloba L.,
      an important landscape and medicinal tree. Callus clumps were incubated on MS
      medium supplemented with high sucrose concentrations (up to 24 percent, w/v),
      employed alone or with ABA (2-10 mg per L) for various durations followed by
      desiccation for 0-240 min and cryopreservation. The beneficial effect of
      preculture on regrowth after desiccation without cryopreservation was only
      observed for the cells with water content of 20 percent FW and was not influenced
      by presence of ABA. However, preculture of calli in presence of ABA resulted in a
      lower desiccation rate as compared with untreated controls and calli pretreated
      with sucrose alone. In calli precultured with sucrose alone, post-thaw regrowth
      was occasional regardless of the sugar concentration in the medium, while
      pretreatment of calli with ABA and sucrose ensured stable regrowth after
      cryopreservation. The highest post-thaw regrowth of 54 percent was achieved for
      calli precultured on medium supplemented with 10 percent (w/v) sucrose and 2 mg
      per L ABA for 21 days followed by desiccation for 150 min. The different effects
      of preculture treatments on post-thaw regrowth were associated with significant
      changes in content and in composition of endogenous soluble sugars in calli.
      Sucrose and glucose accumulated preferentially in ABA-precultured calli, while
      the fructose content was higher in calli precultured in absence of ABA. The
      possible role of preculture on desiccation and cryopreservation tolerance of G.
      biloba cell cultures is discussed.

PMID- 19750249
TI  - Psychiatric symptoms and disorders in HIV infected mine workers in South Africa.
      A retrospective descriptive study of acute first admissions.
AB  - OBJECTIVE: The social and living conditions of mine workers in South Africa
      contribute to a rapid transmission of human immunodeficiency virus (HIV) and
      other sexually transmitted infections. HIV-associated dementia is a serious
      condition during HIV disease. Several other psychiatric symptoms and disorders,
      such as psychosis, secondary mania and depression, have also been associated with
      clinical HIV infection. We describe the onset of psychiatric symptoms and signs
      in a group of untreated, HIV infected male mine workers first admitted for
      psychiatric treatment at the Rand Mutual Hospital in Johannesburg. METHOD:
      Between 1987 and 1997, 38 consecutive cases were admitted, and their files were
      retrieved for study in 2006. The subjects were 38 black male mine workers
      admitted acutely for psychiatric care due to psychiatric symptoms, and
      subsequently diagnosed with HIV infection. The presenting psychiatric symptoms on
      admission and diagnoses at discharge were compiled for all patients, not to infer
      causality but to establish the range of symptoms that the clinician has to deal
      with. RESULTS: The 38 patients presented with a wide range of psychiatric
      symptoms. The dominating symptoms were those of cognitive deficits, and different
      psychotic manifestations. 12 of the patients, almost one third of the
      individuals, were diagnosed with dementia. The patients with dementia exhibited
      cognitive deficits, and in addition often abnormal behaviour and psychotic
      symptoms, and several also had symptoms of secondary mania. 5 of the patients
      presented with delirium. Psychosis, without concurrent dementia, was diagnosed in
      5 patients. Bipolar disorder with mania, without concurrent dementia, and major
      depression was present in 2 patients, respectively. Screening for substance abuse
      showed that 9 of the patients had ongoing cannabis abuse and 10 had alcohol
      abuse. Cannabis-induced psychotic disorder was present in 5 patients. CONCLUSION:
      The findings confirm that patients with a new diagnosis of HIV may present with
      disorders of thought and/or cognition as well as gross behavioural disturbance,
      and that psychotic symptoms and secondary mania could be manifestations of the
      clinical onset of HIV/acquired immune deficiency syndrome (AIDS) infection.

PMID- 19750250
TI  - Occurrence of comorbid substance use disorders among acute psychiatric inpatients
      at Stikland Hospital in the Western Cape, South Africa.
AB  - OBJECTIVE: Little is known about the epidemiology of substance use disorders
      (SUD) among psychiatric inpatients in the Western Cape, South Africa. Therefore,
      this study was conducted to examine the prevalence of SUD among acute adult
      psychiatric inpatients at Stikland Hospital, one of three state acute psychiatric
      hospitals in the Western Cape. METHOD: A prospective descriptive prevalence
      survey was undertaken over a three-month period. During this period, data was
      collected on psychiatric patients (N=298) who were hospitalized in the acute
      psychiatric wards at Stikland. This included patient demography, psychiatric and
      substance use history. Urine was also collected and analyzed for substances
      commonly abused in the Western Cape. RESULTS: A co-morbid SUD (abuse or
      dependence) was diagnosed in 51% of patients. In addition, a diagnosis of a
      substance-induced psychiatric disorder was made in 8% of these patients, 1% of
      who was diagnosed with a substance-induced mood disorder, while 7% was diagnosed
      with a substance induced psychotic disorder. Patients diagnosed with a co-morbid
      SUD were younger than those without a SUD and more likely to have been
      involuntary admissions. These patients also displayed more violence prior to
      admission that contributed to their admission and were more likely to have used
      cannabis or methamphetamine as their preferred drug of abuse. Only a small group
      of patients had documented evidence of any prior interventions for their SUD.
      CONCLUSION: SUD are prevalent among psychiatric inpatients and contribute to
      their morbidity. This has implications for staff training and service
      development.

PMID- 19750251
TI  - Stigma, treatment beliefs, and substance abuse treatment use in historically
      disadvantaged communities.
AB  - OBJECTIVE: Access to substance abuse treatment among historically disadvantaged
      communities (HDCs) in Cape Town, South Africa is limited, despite a growing
      demand for services. Although research has reported on structural barriers to
      treatment access, nonstructural factors remain largely unexplored. The aim of
      this paper is to describe two nonstructural influences on the use of substance
      abuse treatment services for people from HDCs: stigma and negative beliefs about
      treatment. METHOD: Findings from the qualitative component of a multi-method
      study are reported. In-depth interviews were conducted with 20 key informants,
      all of whom worked or lived in HDCs in the greater Cape Town area. Content and
      thematic techniques were used to analyse data. RESULTS: According to key
      informants (i) stigma towards individuals with substance use disorders was
      prevalent in HDCs and negatively impacted on attempts to access services; (ii)
      negative beliefs about the quality and effectiveness of treatment were
      commonplace and acted as barriers to the use of existing services; and (iii)
      several factors contributed to these non-structural barriers including media
      representations of both individuals with substance use disorders and treatment
      facilities for these disorders. CONCLUSION: This paper moves beyond the
      description of structural barriers to treatment to describe how two nonstructural
      factors, stigma and negative beliefs about treatment, hinder treatment seeking
      for substance use disorders. Recommendations for addressing these barriers
      include efforts to (i) shift discourses about substance abuse treatment, (ii)
      improve service quality, and (iii) address myths and misconceptions about
      treatment.

PMID- 19750252
TI  - Occupational disability on psychiatric grounds in South African school-teachers.
AB  - OBJECTIVE: School-teachers are exposed to high levels of stress and have high
      rates of premature retirement on psychiatric grounds. This study investigated
      factors associated with occupational disability due to psychiatric disorders in
      teachers in South Africa. METHOD: This retrospective study investigated 81 school
      teachers in the Cape Town area who had been declared permanently medically
      disabled as a consequence of psychiatric disorders. RESULTS: Patients were
      relatively young (44+/-6.1 yrs), had experienced symptoms for 5.2+/-3.8 yrs, and
      had been treated for 4+/-3.5 yrs. Almost half had a family history of psychiatric
      disorder, and the majority (N = 66. 81%) cited work-related stress as a
      significant contributing factor. Major depressive disorder was the commonest
      diagnosis (83%), and 56% had co-morbid Axis-I diagnoses. Thirty percent had
      prominent underlying obsessive-compulsive personality traits, and 46% displayed
      classroom phobia. CONCLUSION: Work-related stress is a major factor in South
      African teachers with occupational disability on psychiatric grounds.

PMID- 19750253
TI  - Neuropsychiatric complications associated with interferon - alpha -2b treatment
      of malignant melanoma.
AB  - Several adverse effects have been associated with interferon alpha 2b treatment
      and neuropsychiatric effects have also been commonly reported. Psychosis and mood
      disorders have been described in the literature. This case report is of a 30 year
      old man with malignant melanoma stage 3a who was receiving adjuvant alpha 2b
      interferon and developed a manic episode two weeks post switching after one month
      of treatment on a high dose to a low dose. There was no previous psychiatric
      illness and no known family history of mental illness. This is in keeping with
      previous reports that mania has been observed in patients undergoing interferon
      treatment especially after significant dose-reduction or treatment breaks. Mania
      induced by interferon responds well to antimanic drugs .Since interferon alpha 2b
      is now commonly used in the treatment of malignant melanoma and other conditions,
      the need to be aware of its neuropsychiatric complications is essential.

PMID- 19750254
TI  - The profile of mentally ill offenders in Katsina, Northern-Nigeria.

PMID- 19750255
TI  - Adipokines and etiopathology of metabolic disorders.
AB  - White adipose tissue is an endocrine organ producing numerous proteins known as
      adipokines, which include leptin, adiponectin, resistin, visfatin, and other
      factors, which are involved in most metabolic disorders. In obesity, plasma
      leptin concentrations are high due to leptin resistance that may result from the
      attenuation of leptin signaling in the hypothalamus. Leptin acts to inhibit
      appetite, stimulate thermogenesis, enhance fatty acid oxidation, decrease
      glucose, and reduce body weight, and fat. A reduced adiponectin level has been
      associated with insulin resistance, dyslipidemia, and atherosclerosis, and its
      low level is a predictor of later development of type 2 diabetes. Resistin
      expression is low in adipose tissue and high in bone marrow and lungs, its role
      in glucose homeostasis remains controversial, it has been associated with insulin
      resistance and obesity. Visfatin is a secretory protein highly enriched in
      visceral adipocytes, liver, muscle, and lymphocytes. An increase of visfatin
      levels in obesity was related to preservation of insulin sensitivity, it enhances
      glucose uptake by adipocytes and inhibits hepatocyte glucose release, it induces
      tyrosine phosphorylation, and interacts with insulin receptors. Many studies are
      still being conducted to highlight the role of adipokines in metabolic disorders.

PMID- 19750256
TI  - Airway management for cervical spine injury.
AB  - In this review, important factors related to initial management, diagnosis,
      airway, and anesthetic management of patients with cervical spine injury (CSI)
      are discussed. Early diagnostic and clinical evaluation is important in excluding
      CSI. In-line stabilization reduces movement of the cervical spine. Tracheal
      intubation under fiberscopic control, offers safety, and comfort to the patient.
      However, in cases of severe deterioration of vital functions, intubation must be
      performed without any delay at the site of the accident or in the emergency room.
      Early airway management and maintenance of spinal immobilization are more
      important factors in limiting the risk of secondary neurological injury than any
      particular technique. The current opinion is that oral intubation after
      intravenous induction of anesthesia and muscle relaxation along with in-line
      stabilization is the safest and quickest way to achieve intubation in a patient
      with suspected CSI.

PMID- 19750257
TI  - Development of a new high performance liquid chromatography method for
      measurement of coenzyme Q10 in healthy blood plasma.
AB  - OBJECTIVE: To improve a new high performance liquid chromatography (HPLC) method
      for coenzyme Q10 (CoQ10) measurement in human plasma. METHODS: We conducted this
      study in the Chemistry and Biochemistry Department, College of Medicine, Al
      Nahrain University, Baghdad, Iraq from September 2004 to July 2005. Sixty healthy
      volunteers aged 28.51+/-7.30 years were participated in this study. All
      participants were non-smokers and under no any treatment for the last 3 days and
      fast for 12 hours before analysis. Coenzyme Q10 levels were measured by improved
      isocratic reversed phase HPLC technique after one-step ice-cold 1-propanol
      extraction step. RESULTS: The ultra violet (UV) detection, developed HPLC method
      gives a good linearity range between 0.1-4.0 mg/L. The coefficients of variations
      (CVs%) of within-day precision for CoQ10 in human plasma were 0.2-3.90%.
      Analytical recoveries were 95.5-101.30%, whereas the average CV% of CoQ10
      reproducibility was 0.959%. CONCLUSION: A new improved rapid, precise, and
      sensitive HPLC method for the quantitation of CoQ10 is suitable for analysis of
      blood plasma samples.

PMID- 19750258
TI  - Safety of umbilical cord blood-derived mesenchymal stem cells (MSCs) following 5
      azaserine induction and inhibition of human cardiac myocyte apoptosis by MSCs.
AB  - OBJECTIVE: To further study the safety and effect of the umbilical cord blood
      (UCB)-derived mesenchymal stem cells (MSCs) on apoptosis of human cardiac myocyte
      (HCM). METHODS: The UCB was collected at the time of delivery with informed
      consent obtained from 10 donors. The UCB-derived MSCs was treated with 5
      azaserine (5-AZA), and further introduced differentiation into cardiomyocytes.
      The telomerase activity, G-banding patterns of chromosomal karyotypes, tumor
      formation in nude mice, reverse transcription polymerase chain reaction (RT-PCR),
      and the inhibited apoptosis of UCB-derived MSCs were further investigated. This
      study was carried out in the laboratory of Beijing Shijitan Hospital, Beijing,
      China and Inheritance Research Section of Chinese Medical Institute, Beijing,
      China from July 2005 to December 2007. RESULTS: The MSCs-derived from UCB were
      differentiated into cardiomyocytes in vitro, possessed telomerase activity after
      5-AZA induction, and no abnormal chromosomal karyotypes were observed. Expression
      of p53, cyclinA, cdk2, -actin, C-fos, h-TERT and c-myc were similar in MSCs
      before and after 5-AZA treatment. There was no tumor formation injected into nude
      mice. The UCB-derived MSCs significantly inhibited apoptosis of human
      cardiomyocytes. CONCLUSION: Umbilical cord blood-derived MSCs are safe and
      effective source of cell-transplantation treatment, and can inhibit the apoptosis
      of human cardiomyocytes in co-cultured.

PMID- 19750259
TI  - Oxidative stress and nitric oxide deficiency in inflammation of chronic renal
      failure. Possible preventive role of L-arginine and multiple antioxidants.
AB  - OBJECTIVE: To evaluate the effect of L-arginine and multiple antioxidants on the
      inflammatory cytokines level, renal functions, blood pressure and dyslipidemia in
      chronic renal failure (CRF) rats. METHODS: This study was carried out between
      December 2007 and November 2008 in the Department of Physiology, Faculty of
      Medicine, King Saud University, Kingdom of Saudi Arabia. Chronic renal failure
      was induced in 40 rats by renal mass reduction (RMR) and 10 rats were sham
      operated. Renal mass reduction rats were treated for 12 weeks by L-arginine
      and/or a mixture of antioxidants (L-carnitine, Catechin, Vitamins E and C) and
      the effect of the treatments on plasma cytokines, soluble intercellular adhesion
      molecule-1 (sICAM-1), nitrate (NO2) and nitrites (NO3), lipid profile, blood
      pressure, and renal function was examined. RESULTS: Chronic renal failure
      increased plasma Interleukin (IL)-1alpha, IL-1beta, IL-6, tumor necrosis factor
      alpha, soluble intercellular adhesion molecule-1 (sICAM-1) levels and decreased
      anti-inflammatory cytokines IL-4 and 10 levels. In addition, hypertension, and
      dyslipidemia were found. L-arginine treatment improved kidney functions,
      decreased systolic blood pressure and decreased inflammatory cytokines levels.
      Antioxidants administration decreased inflammatory cytokines and sICAM-1 levels
      and increased IL-4 levels. Combined use of L-arginine and the antioxidants
      mixture were very effective in their tendency to recover normal values of kidney
      functions, plasma cytokines, sICAM-1, blood pressure, NO2/NO3, cholesterol and
      triglycerides concentrations. CONCLUSION: Restoration of the pro-oxidant/
      antioxidants balance with increased NO bio-availability counteracts inflammation,
      renal impairment and dyslipidemia in CRF. This may open new perspectives for the
      role of antioxidants and NO precursors in the treatment of uremia and its
      complications.

PMID- 19750260
TI  - The accurate prediction of rare hemoglobin variants using a combination of high
      performance liquid chromatography, retention time and isoelectric focusing
      electrophoresis position.
AB  - OBJECTIVE: To investigate the predictive accuracy of using a combination of the
      high pressure liquid chromatography (HPLC) retention time and the relative
      isoelectric focusing (IEF) position to diagnose rare hemoglobin variants.
      METHODS: A selected group of 40 patients with a rare beta-chain variant were
      assigned a presumed diagnosis following HPLC and IEF screening and then the
      variant identified in each case by DNA analysis. The study was conducted at the
      National Hemoglobinopathy Reference Laboratory, Oxford, United Kingdom, from
      August 2008 to October 2008. RESULTS: Thirteen out of 14 different variants were
      predicted accurately in 39 (97.5%) cases, compared to only one each for HPLC and
      IEF when used individually. A novel amplification refractory mutation system
      polymerase chain reaction test was developed for Hb J-Baltimore and used
      successfully, to provide a simple, rapid, and inexpensive diagnosis. CONCLUSION:
      The use of both HPLC retention time and isoelectric focusing position provides an
      accurate presumed diagnosis of a rare hemoglobin variant in the majority of
      cases. Amplification refractory mutation system-polymerase chain reaction test
      can provide a simple, rapid and inexpensive molecular diagnostic method for rare
      beta-chain variants.

PMID- 19750261
TI  - Can aspirin protect or at least attenuate gentamicin ototoxicity in humans?
AB  - OBJECTIVE: To investigate and prove that Aspirin as an antioxidant protects, or
      at least attenuates Gentamicin ototoxicity in humans. METHODS: A prospective,
      randomized, double-blind trial was conducted in 60 patients that completed all
      requirements. This study was conducted in the Department of Otolaryngology and
      Orthopedics, Besat Hospital, Hamadan University of Medical Sciences, Hamadan,
      Iran, between December 2007 and November 2008. The patients were divided into 2
      groups, the experimental and the control groups that were similar with respect to
      gender, age, and weight. The treatment group received 1.5 g/day (500 mg every 8
      hours) Aspirin, and the control group received placebo similar to the other
      group. RESULTS: Comparison of the pure tone audiometry (PTA) at 1000 Hertz (Hz)
      (p=0.03), 2000 Hz (p=0.003), 4000 Hz (p=0.001), and 8000 Hz (p=0.0010) showed
      significant differences between mean of PTA at the beginning, 8th, and 15th day.
      The threshold of PTA at 250 Hz was significantly different only at the 8th and
      15th day (p=0.004), also at the frequency of 500 Hz, the difference between the
      beginning within 15th day and 8th day with 15th day was significant (p=0.001).
      CONCLUSION: In the present study, we had shown that Aspirin can protect the
      ototoxic effect of gentamicin in patients.

PMID- 19750262
TI  - Work-related respiratory symptoms and pulmonary function tests in Iranian
      printers.
AB  - OBJECTIVE: To assess lung function tests and self-reported frequency of work
      related respiratory and allergic symptoms among subjects working as printers.
      METHODS: This study was carried out from June to October 2007 in Mashhad city,
      Iran. The frequency of work-related respiratory and allergy symptoms was studied
      in a sample of 73 printers (group I), and 73 matched controls (group II) using a
      questionnaire in the past year. Pulmonary function tests (PFT) were also measured
      in group I and group II. RESULTS: A total of 30 (41%) subjects from group I
      reported work-related respiratory symptoms. Breathlessness (30%) and cough (27%)
      was the most common symptoms, and 16.5% in group I reported wheezing during work.
      All respiratory symptoms in group I were significantly greater than those in
      group II (p=0.04 to p=0.002). Allergic symptoms (except urticaria) were also
      significantly greater in group I than those in group II (p=0.048 to p=0.009). In
      addition, respiratory and allergic symptoms were greater during work compared
      with the rest period, which was significant for cough, breathlessness, and runny
      nose (p<0.21 to p<0.049 for all cases). All PFT values were also significantly
      lower in group I compared to group II (p=0.006 to p<0.0001). CONCLUSION: Printing
      work is associated with a high frequency of work related respiratory and allergic
      symptoms particularly during work period. The PFT values were also significantly
      reduced among subjects in group I.

PMID- 19750263
TI  - Role of intravenous extra fluid therapy in icteric neonates receiving
      phototherapy.
AB  - OBJECTIVE: To evaluate the role of intravenous extra fluid therapy in
      accelerating the reduction of jaundice in newborns who received phototherapy.
      METHODS: This study was performed on 100 terms, jaundiced neonates who had a
      total bilirubin of 18 mg/dl or more in the Pediatrics Ward of Ghaem Hospital,
      Mashhad, Iran from October 2007 to April 2008. The patients were randomly divided
      into 2 equal groups; group I (case group) were given extra parenteral fluid
      besides breast feeding, and group II (control group) received only breast milk.
      The rate of bilirubin decrement, length of hospital stay, and rate of blood
      exchange were compared. RESULTS: The rate of serum bilirubin decrease per hour in
      the first 12 hours after admission in group I (0.41 mg/dl [95%CI 0.1] versus 0.38
      mg/dl in group II [95% CI 0.3], [p=0.22]). It was 0.41 mg/dl for group I (95% CI
      0.0001), and 0.21 mg/dl (95%CI 0.06) for group II in the second 12 hours
      (p=0.02). After 24 hours, it was 0.38 mg/dl in group I (95% CI 0.0001), and 0.29
      mg/dl in group II (95% CI=0.09) (p=0.037). The mean hospital stay was 68.5 hours
      in group I, and 67.4 hours in group II (p=0.95). CONCLUSION: Additional
      parenteral fluid therapy in icteric newborns can accelerate reduction in serum
      bilirubin levels in the first 24 hours.

PMID- 19750264
TI  - The evaluation of relationship between group A streptococcal infection with tic
      disorders in children.
AB  - OBJECTIVE: To evaluate the relationship between group A beta hemolytic
      streptococcus infection (GABHS) and tic disorders in children. METHODS: This is a
      case-control study that was conducted in Child and Adolescent Psychiatric Clinic,
      Isfahan, Iran, between May 2008 and February 2009. Thirty-six children (aged 5
      15) with tic and 36 children without tic and obsessive-compulsive disorder (OCD)
      were investigated for clinical and laboratory signs of GABHS. The tools utilized
      in this research were clinical interview according to the DSM IV-TR and
      laboratory tests (throat culture, rapid antigen detection test [RADT], anti
      streptolysin O [ASO] and yale global tics severity scale [YGTSS]). The control
      group was of the same gender and age as the tic group who had come to the clinic
      for other illnesses and was in need of blood test. None of the subjects in the
      case and control groups had a clinical history of GABHS infection. RESULTS: The
      relationship between tic disorder and GABHS infection (if any of these laboratory
      tests takes place: throat culture, RADT, ASO > or = 250) in the tic group was 16
      (44.4%) and in the control group was 9 (25%), there were significant differences
      (p<0.05). No significant correlation was found between ASO titer and YGTSS
      scores. The specificity of RADT was 100%. CONCLUSION: The result showed
      correlation between GABHS infection and tic disorder, but it does not mean that
      GABHS infection caused tic disorder.

PMID- 19750265
TI  - Pediatric heart diseases in Madina, Saudi Arabia. Current status and future
      expectations.
AB  - OBJECTIVE: To demonstrate the magnitude of pediatric heart disease problem in
      Madina, current situation of heart service, obstacles and future expectations.
      METHODS: We conducted this cross sectional study in Madina Maternity and Children
      Hospital, Madina, Kingdom of Saudi Arabia from January 2007 to June 2008. The
      study was approved by the Ethical Committee. A computer based program was
      established to register the data of all children attended the pediatric
      cardiology unit. RESULTS: A total of 4348 children were seen in the study period;
      2301 were follow up cases while 2047 were new cases. Of the new cases, 794
      (38.8%) were found to have heart diseases. Of this, 705 have CHD
      (cardiomyopathies 34, rheumatic heart disease 26, mitral valve prolapse 15,
      Kawasaki disease 9, and arrhythmia 5). Ventricular septal defect was the most
      common CHD (34.5%), and followed by atrial septal defect (8.9%). Other CHDs were
      as follows pulmonary stenosis (7.9%), patent ductus arteriosus (6%),
      atrioventricular septal defect (3.8%), aortic stenosis (3.5%), dextro
      transposition of great arteries (3.5%), tetralogy of fallot (3%), coarctation of
      aorta (2.8%), and others (26%). Three hundred and ten patients required referral
      to the cardiac centers in Riyadh for catheterization or surgical intervention.
      Urgent referral was required in 128 patients. All patients were transferred via
      medical evacuation service. CONCLUSION: Pediatric heart disease constitutes a
      major health problem in Madina. The majority of patients have CHD. The need for
      cardiac centre in Madina was emphasized to avoid problems of transportations.

PMID- 19750266
TI  - Childhood lymphomas in Yemen. Clinicopathological study.
AB  - OBJECTIVE: To find out the frequency of childhood lymphomas in all ages, and to
      describe patterns of lymphomas in relation to gender and site in Yemen. METHODS:
      This is a descriptive record-based study of 1167 cases of lymphomas diagnosed by
      3 pathologists in the Department of Pathology, Sana'a University, Sana'a, Yemen
      from 1st January 2004 to 30th December 2007. The diagnoses were made on
      hematoxylin and eosin stained, and categorized non-Hodgkin's lymphoma (NHL)
      according to the National Cancer Institute Working Formulation classification,
      and Hodgkin's disease (HD) according to Rye classification. RESULTS: Out of 1167
      lymphomas, 801 (68.6%) were NHL, and 366 (31.4%) were HD, amongst these 347
      (29.7%) were patients aged < or = 18 years, and 221 (63.7%) had NHL, and 126
      (36.3%) had HD. The NHL found was Burkitt (64.8%), diffuse large cell lymphoma
      (23%), lymphoblastic lymphoma (6.3%), and other miscellaneous types account for
      5.9%. The histological types of HD were mixed cellularity (72.3%), lymphocyte
      predominance (16.6%), nodular sclerosis (7.9%), lymphocyte depletion (0.8%), and
      nonclassified cases (2.4%). The female to male ratio was 1:1.7. The nodal site
      accounts for 205 (59%) cases, and 142 (41%) were extranodal. The HD was totally
      nodal, whereas NHL showed 37.4% nodal, and 62.6% extranodal. CONCLUSION:
      Childhood lymphomas in this study is of high grade NHL, and of less favorable
      prognostic type in HD. This indicates that childhood lymphomas in Yemen have
      similar patterns as that found in other international studies.

PMID- 19750267
TI  - Importance of ophthalmological examination in children with congenital
      sensorineural hearing loss.
AB  - OBJECTIVE: To evaluate the importance of ophthalmological examination in children
      with congenital sensorineural hearing loss (SNHL). METHODS: This study was
      conducted at the Ear, Nose, and Throat Department of Al-Ramadi Teaching Hospital
      in Al-Ramadi city, Iraq from 20 December 2007 to 30 October 2008. Fifty children
      with congenital SNHL were included in this prospective study. Ophthalmological
      examination was carried out for all patients. RESULTS: Out of 50 patients with
      SNHL, 16 (32%) had ocular abnormalities. Ocular abnormalities were more common in
      postlingual age group (81.3%) than other age groups, which is statistically
      significant (p=0.007). Myopia was the most common abnormality that was present in
      5 patients (31.3%). The results showed that hyperopia was found in 2 patients
      (12.5%), squint in 2 patients (12.5%), retinitis pigmentosa 2 patients (12.5%),
      and blepharitis in 1 (6.3%) patient. Four other patients had multiple
      abnormalities: one with myopia and astigmatism, one with hyperopia and
      conjunctivitis, one with bilateral blepharitis, and allergic conjunctivitis, and
      the last one with myopia and blepharitis. Two children on examination of the eyes
      was diagnosed with Usher syndrome. CONCLUSION: Ocular abnormalities are a common
      problem in children with congenital SNHL necessitating ophthalmological
      examination to detect any abnormal visual acuity, and aid in the diagnosis of
      congenital deafness syndromes.

PMID- 19750268
TI  - Early outcomes of isolated coronary artery bypass grafting in Chinese aged
      patients with diabetes mellitus.
AB  - OBJECTIVE: To compare the early outcomes of coronary artery bypass grafting
      (CABG) in aged diabetic patients, and evaluate the affection of diabetes on the
      early outcomes of CABG in aged patients. METHODS: The study took place in the
      Department of Cardiovascular Surgery, Shanghai Jiao Tong University Affiliated
      First People's Hospital, Shanghai, China, between January 2000 and July 2008.
      Five hundred and ninety-three elderly patients (age > or = 70-years-old),
      undergoing isolated CABG were retrospectively divided into diabetic group and non
      diabetic group. We analyzed the pre-operative, intra-operative, and post
      operative variables of the 2 groups. The t-test, Chi-square test, and
      multivariate logistic regression were used to determine the differences between
      the 2 groups of patients. RESULTS: There was no statistical difference of pre
      operative and intraoperative variables between the 2 groups, except that there
      were more left main coronary artery diseases in the diabetic group. Values in the
      post-operative period such as morbidity, complications, and blood infusion had no
      differences between the 2 groups. Diabetes mellitus and age are not the risk
      factors for in-hospital mortality. CONCLUSION: Coronary artery bypass grafting in
      elderly patients is plausible. Furthermore, diabetic patients could get the same
      surgical results as those non-diabetic patients.

PMID- 19750269
TI  - Attitudes, knowledge, and practices in relation to cervical cancer and its
      screening among women in Saudi Arabia.
AB  - OBJECTIVE: To assess the knowledge, attitude, and practices related to cervical
      cancer screening, and its underlying etiology and preventive measures among women
      living in the Kingdom of Saudi Arabia. METHODS: Six hundred self-administered
      questionnaires were distributed to randomly selected women from different groups
      in the general population of Jeddah, Kingdom of Saudi Arabia. These
      questionnaires were sent out to school teachers, relative, friends, as well as,
      through direct interview of patients visiting the outpatient clinic while
      awaiting for their appointments at the King Abdul-Aziz University Hospital from
      January to March 2008. There were 500 respondents (83.3%). RESULTS: The knowledge
      of the human papilloma virus (HPV) as an etiological agent for cervical cancer
      was expressed by 72 (14.4%), and the HPV vaccine by 49 (9.8%) of the respondents.
      Whereas, 338 (67.6%) of the respondents were aware of the Pap smear, however,
      only 84 (16.8%) had undergone the test. The main reason for not having a Pap
      smear was the lack of awareness. CONCLUSION: The awareness on cervical cancer
      among women in Saudi Arabia is far behind that in the developed countries. There
      is a need to educate and promote awareness of cervical cancer in this population.

PMID- 19750270
TI  - Prevalence and antimicrobial resistance of health care associated bloodstream
      infections at a general hospital in Saudi Arabia.
AB  - OBJECTIVE: To determine the trend of health care associated blood stream
      infection (HA-BSI) at Saudi Aramco Medical Services Organization. METHODS: This
      prospective survey was conducted during the year 2002-2006. Definitions of HA-BSI
      infections were based on the Centers for Disease Control and Prevention
      categories. RESULTS: There were a total of 1103 distinct episodes of HA-BSI with
      annual average rates of 8.5 per 1000 discharges and 18 per 10,000 patient-days.
      Of all episodes, 38% were primary, 47% were central line-associated bloodstream
      infection (CLABSI), and the remaining 15% were secondary bacteremias. The
      hospital wide BSI rate per 1000 discharges increased from 7.8 to 11.9 (p<0.001).
      Secondary bacteremia remained relatively stable over the study period at 3/10,000
      patient-days (p=0.41). Primary BSI increased from 6.9 to 10.6 per 10,000 patient
      days (p<0.001). Hospital wide CLABSI increased from 3.2 to 6 per 1000 discharges
      (p<0.001) and from 7 to 11.8 per 10,000 patient-days (p=0.039). Coagulase
      negative staphylococcus was the leading pathogen (23.7%) followed by
      Staphylococcus aureus (11.1%) and Escherichia coli (11.1%). Of all episodes,
      candida caused 5%, Klebsiella pneumoniae (9%) and Pseudomonas aeruginosa (7.3%).
      CONCLUSION: The rate of secondary BSI remained relatively stable over the study
      period. However, primary BSI and CLABSI increased over time. Coagulase negative
      staphylococcus, Staphylococcus aureus, and Escherichia coli were the most
      frequent microorganisms.

PMID- 19750271
TI  - Graduate-entry medical students' self-directed learning capabilities in a problem
      based curriculum.
AB  - OBJECTIVE: To explore junior and senior students' perceptions of their self
      directed learning (SDL) capabilities in an innovative graduate-entry medical
      program and to determine the construct reliability of the survey instrument
      utilized. METHODS: A cross-sectional survey design in which a self-report
      questionnaire was administered to undergraduate medical students (n=43) of King
      Saud bin Abdul Aziz University for Health Sciences, Riyadh in October 2008 and
      March 2009; soon after entry and in their year 3 of an integrated problem-based
      learning (PBL) program. The questionnaire sought self-assessment on 14 SDL
      capabilities. RESULTS: Questionnaire construct reliability was high (Cronbach's
      alpha=0.945). Respondents had medium to high perceptions of their self-directed
      learning capabilities in areas that are among the main building-blocks of self
      directed learning. In comparison to junior students, senior students had
      statistically significantly higher mean scores on 11 of 14 self-assessed SDL
      competencies (p<0.05). CONCLUSION: Consistent with other studies of SDL in a
      graduate-entry PBL curriculum, most students perceived themselves as having
      moderate to high SDL capabilities. Knowledge of learners' perceived levels of
      self-directedness is helpful for both students and medical educators. By
      understanding learners' conceptions of their self-directed learning capabilities
      we can design evidence-based program modifications that are likely to promote
      intended curriculum objectives. Longitudinal studies are needed observing the
      application and stability of perceived capabilities.

PMID- 19750272
TI  - Hypokalemia-associated catastrophic rhabdomyolysis in ulcerative colitis.
AB  - A case of catastrophic hypokalemia-associated rhabdomyolysis in patient with
      ulcerative colitis (UC) is reported. A 60-year-old man presented with an
      exacerbation of UC and hypokalemia due to long-term diarrhea. While in the
      hospital, rhabdomyolysis developed in association with worsening hypokalemia. The
      hypokalemia was refractory to treatment and progressive course. Patient developed
      painful cramps of the masticatory and facial musculature associated with a
      moderated weakness in distal muscle groups. The weakness extended to intercostals
      and diaphragm muscles and led to respiratory deficiency. Serum concentration of
      creatine kinase was highly increased. Patient died from advancing and
      insurmountable cardiovascular deficiency. The causative role of hypokalemia for
      muscle involvement and rhabdomyolysis in patients with inflammatory bowel
      diseases was discussed.

PMID- 19750273
TI  - Infliximab treatment for resistant Achilles tendonitis.
AB  - Undifferentiated spondyloarthropathies USPA can sometimes be refractory to usual
      disease modifying agents. Anti-tumor necrosis factor TNF-alpha agents have been
      shown to be effective in spondyloarthropathies. Few articles described the
      efficacy of TNF-alpha antagonists in USPA. Our patient had refractory Achilles
      tendonitis as an early manifestation of USPA which responded dramatically to
      infliximab treatment.

PMID- 19750274
TI  - Perforated acute appendicitis complicated by multiple intraabdominal abscesses
      caused by Enterococcus Avium in a non-compromised child.

PMID- 19750275
TI  - Effect of nigella (Nigella sativa L.) seeds on hematological parameters in rats.

PMID- 19750276
TI  - Retinoic acid induced chordomas as a model of differential therapy.

PMID- 19750277
TI  - Our traumatic cataract experience in patients with hospitalizing ocular trauma.

PMID- 19750278
TI  - Juvenile systemic lupus erythematosus in Bahrain. A tertiary referral center
      experience.

PMID- 19750279
TI  - Resistance patterns of bacterial isolates to antimicrobials in the United Arab
      Emirates.

PMID- 19750280
TI  - Nutritional knowledge of primary health care physicians in Jeddah, Saudi Arabia.

PMID- 19750281
TI  - The stepped hybrid plate for carpal panarthrodesis - Part I: relationship between
      plate and bone surfaces.
AB  - In the 1990s, the AO (Arbeitsgemeinschaft fur Osteosynthesefragen) Hand Study
      Group developed several anatomically bent plates (standard and short) for wrist
      panarthrodesis in humans. However, only straight plates have been used for carpal
      panarthrodesis (CP) in animals to date. The primary purpose of this study was to
      determine if precontoured plates are more anatomical for CP in dogs. Measurement
      of several of the bones that are implicated in CP, as well as the relationship
      between their surfaces and the surface of a straight plate, were performed in a
      radiographic and computed tomographic cadaveric study. Axial and transverse
      measurements taken at different levels of the metacarpal bones 2, 3 and 4 were
      also included. The second objective of this study was to develop a more
      anatomical CP plate according to the results obtained. The measurements and
      images obtained in this study show that, as in human orthopaedics, bent or
      stepped plates are more anatomically correct than straight plates for CP in dogs.

PMID- 19750282
TI  - Repair of thirty-six fractures in dogs using the Mennen clamp-on plate:
      preliminary results.
AB  - OBJECTIVE: To report the use of a human fixation device, the Mennen clamp-on
      plate (MCOP), for fracture repair in dogs as the sole method of fixation, or in
      combination with another fixation method such as an intramedullary pin. METHODS:
      The study, which was performed to evaluate the use of the MCOP in fracture repair
      in dogs, included 36 cases that were selected between 2004 and 2008. The selected
      cases were all closed diaphyseal fractures, in which sufficient plate prongs
      could engage the bone on either side of the fracture. RESULTS: Of the 36 cases,
      32 had excellent outcomes, and four had complications; these were two cases of
      fixation failure, one case of osteomyelitis, and one with mild sciatic nerve
      deficits. DISCUSSION: The MCOP is a promising method for fracture repair on its
      own for young puppies (six months or less), and in conjunction with other
      fixation methods in older dogs. It is quick to apply, as no screw holes are
      created and it achieved a successful outcome in 95% of the cases, provided the
      cases were appropriately selected for this method. CONCLUSIONS: Using the MCOP
      has produced promising preliminary results in this study and warrants further
      evaluation.

PMID- 19750283
TI  - The stepped hybrid plate for carpal panarthrodesis - Part II: a multicentre study
      of 52 arthrodeses.
AB  - Fifty-two carpal panarthrodeses (CP) were carried out in 44 dogs (eight
      bilateral), in a multicentre study using a single (n = 47) or double (n = 5)
      stepped hybrid CP plate. Of these 44 cases, 39 were between 20-55 kg in
      bodyweight , 26 were males , and the carpometacarpal was the most common joint
      involved. Falling and other impact trauma were the most common aetiology. Pain of
      unknown origin, carpal luxation, chronic accessory carpal bone fracture, distal
      comminuted intra-articular radial fracture, bone tumour, degenerative joint
      disease, canine erosive idiopathic polyarthritis, avascular necrosis of the
      radial carpal bone and fractures of several metacarpal bones were some of the
      pathologies reported. Fracture of the third metacarpal bone during screw
      insertion was the only intrasurgical complication. Malpositioning of the plate or
      screws and over-tightened screws were technical errors observed in seven of the
      procedures. The radial carpal bone was not fixed with a screw in two cases due to
      bone deformity. Concurrent plate breakage and bending in the same patient
      operated on bilaterally was observed during the follow-up period, which
      represented a major complication rate of 3.8% for all procedures. Minor
      complications were: low grade infection, lick granuloma, digit hyperextension,
      screw loosening or failure, incomplete fusion of some joints and a fracture of
      the third metacarpal bone at the distal screw hole of the plate; which
      represented a rate of 44.2% on all procedures. Complete carpal healing was
      observed radiographically in 94.2% of all procedures. Limb function was excellent
      to good, and all of the owners, except for one, were satisfied with the
      procedure.

PMID- 19750284
TI  - Spontaneous recovery of experimental valgus deformity in lambs.
AB  - INTRODUCTION: Angular deformity in the growing skeleton of animals, especially in
      the radius and ulna, is occasionally seen in clinical practice. The mechanism of
      spontaneous correction of these angular deformities however remains to be
      elucidated. The purpose of our experiment was to explore the ability of a growth
      plate to correct an induced valgus deformity, and to study the mechanism of
      correction. METHODS: Before beginning the study, valgus deformity of the distal
      radius had been induced in lambs by the application of a device that causes
      asymmetrical compression of the growth plate. The study began after removal of
      the device and spontaneous correction of the induced deformity was observed
      weekly for 20 weeks. The angles of the deformity and longitudinal growth on the
      medial and lateral portions of the growth plate were respectively measured on
      craniocaudal and mediolateral radiographs. RESULTS AND CONCLUSIONS: Spontaneous
      correction of the valgus deformity occurred during the first 16 weeks. It
      resulted from asymmetrical growth characterised by restricted activity of the
      medial portion of the growth plate (14.8%) in comparison to the lateral portion
      of the experimental radius, and also in comparison to the medial portion of the
      control radius.

PMID- 19750285
TI  - A review of osteoarthritis and obesity: current understanding of the relationship
      and benefit of obesity treatment and prevention in the dog.
AB  - Obesity is an increasingly important health problem for both man and dog.
      Osteoarthritis (OA) is a significant cause of pain and disability in both
      species. A link between obesity and OA has been established in man, though the
      exact mechanism of the relationship remains to be fully elucidated - current
      research supports both biomechanical and biochemical theories. There is good
      evidence (class I*) to support weight loss as an effective treatment for human
      knee OA. In the dog, the relationship is just beginning to be investigated. The
      results of one study in dogs (class IV evidence*) suggest that preventing the
      development of overweightness and obesity reduces the prevalence of hip dysplasia
      and OA of the hip and other joints. Three other studies (class III and IV
      evidence*) support weight loss as an effective treatment for OA in affected
      overweight and obese dogs. Further research could yield greater understanding of
      the pathophysiology of this relationship, perhaps identifying novel therapeutic
      targets. Confirmation and better understanding of the positive effect of treating
      and preventing obesity on symptoms and prevalence of OA is likely to be valuable
      in the campaign against canine obesity.

PMID- 19750286
TI  - Use of a single-ring transarticular fixator construct for immobilisation of the
      talocrural joint following common calcaneal tenorrhaphy.
AB  - OBJECTIVE: To describe the use of a single-ring transarticular fixator construct
      for use in immobilisation of the talocrural joint in order to protect the healing
      of surgical repair of ruptures of the common calcaneal tendon. METHODS: Ten
      repairs were performed in nine dogs. The age, breed, sex, details about the
      duration of pre-existing lameness, and the location and severity of tendon
      rupture at presentation were recorded for each dog. Recheck examinations were
      performed at one, two, four, six, eight, and 12 weeks postoperatively. At each
      visit up to and including six weeks, radiographs of the affected limb were taken.
      Fixators were removed after a mean of 5.9 weeks. Complications were documented
      and classified as major or minor. Major complications were those that required an
      additional surgical intervention. RESULTS: All repairs progressed to a
      satisfactory outcome. While eight of the 10 repairs developed some type of
      complication, only two required surgical intervention. In one repair, seroma
      formation necessitated drain placement and the other developed severe
      periarticular tarsal swelling necessitating early removal of the fixator.
      Lameness scores overall increased during the initial six weeks, however lameness
      quickly resolved following fixator removal. At 12 weeks postoperatively, all
      tendons had healed. The lameness had fully resolved in eight of 10 repairs and
      had drastically decreased in the remaining two. CLINICAL SIGNIFICANCE: A single
      ring transarticular fixator construct is a reliable means of immobilising the
      talocrural joint following surgical repair of the common calcaneal tendon.
      Periarticular tissue swelling is common but typically mild.

PMID- 19750287
TI  - Crescentic osteotomy for resection of oral tumours in four dogs.
AB  - Rim resection of mandibular tumours and a simplified technique using a biradial
      osteotomy blade for maxillary tumours in dogs has not previously been described.
      The medical records and radiographs of dogs with mandibular (n = 3) or maxillary
      (n = 1) tumours resected using crescentic osteotomies were reviewed. The owners
      of two of the dogs reported excellent outcomes without any long-term
      complications or tumour recurrence. The goal of this study was to describe the
      surgical technique for performing a crescentic osteotomy for resection of
      maxillary and mandibular tumours. This technique for resection of mandibular and
      maxillary tumours is clinically applicable in carefully selected cases.

PMID- 19750288
TI  - Repair of long-bone fractures in cats and small dogs with the Unilock mandible
      locking plate system.
AB  - OBJECTIVES: To retrospectively evaluate stabilisation of long-bone fractures in
      cats and small dogs using the Unilock system. METHODS: Medical histories and
      radiographs of consecutive patients with long-bone fractures stabilised with the
      Unilock system were reviewed. Cases with follow-up radiographs taken at least
      four weeks postoperatively were included. Signalment of the patient, fracture
      localisation and type, primary fracture repair or revision surgery, single or
      double plating, and complications for each patient were noted. Additionally,
      implant size, number of screws, number of cortices engaged with screws, and
      number of empty holes across the fracture were evaluated in fractures where a
      single plate had been applied. RESULTS: Eighteen humeral, 18 radial, 20 femoral,
      and 10 tibial fractures were treated. The Unilock system was used for primary
      repair in 44 fractures and for revision surgery in 22 fractures. Two plates were
      applied in 17 fractures, and a single plate was applied in 49 fractures. Follow
      up radiographs were taken four to 109 weeks postoperatively. Complications were
      seen in 12 animals and 13 fractures (19.7%). Fixation failure occurred in seven
      fractures (10.6%). Cases with a single plate that suffered fixation failure had
      thinner screws in relation to bone diameter than cases with double plates, and
      more screws in a main fragment than those without fixation failure. CLINICAL
      SIGNIFICANCE: The Unilock system is a suitable implant for fracture fixation of
      long bones in cats and small dogs.

PMID- 19750289
TI  - Spinal instability resulting from bilateral mini-hemilaminectomy and
      pediculectomy.
AB  - A four-year-old male Dachshund was presented with pelvic limb paresis due to
      intervertebral disc extrusion. The spine was surgically explored and decompressed
      by a bilateral mini-hemilaminectomy and intervertebral disc fenestration at T12
      13, and a bilateral pediculectomy of T13. Five days post-operatively, the dog
      deteriorated because of T13 dorsal laminar subluxation and secondary spinal cord
      compression. This was surgically investigated and stabilised using bilateral
      articular facet positional screws and a dorsal spinal plate; the dog subsequently
      recovered well. Clinically significant spinal instability associated with mini
      hemilaminectomy and pediculectomy surgery has not been reported previously.

PMID- 19750290
TI  - Chondrogenic potential of mesenchymal stromal cells derived from equine bone
      marrow and umbilical cord blood.
AB  - OBJECTIVE: Orthopaedic injury is the most common cause of lost training days or
      premature retirement in the equine athlete. Cell-based therapies are a potential
      new treatment option in musculo-skeletal diseases. Mesenchymal stromal cells
      (MSC) have been derived from multiple sources in the horse including bone marrow
      and umbilical cord blood. The objective of this study was to provide an in vitro
      comparison of the chondrogenic potential in MSC derived from adult bone marrow
      (BM-MSC) and umbilical cord blood (CB-MSC). RESULTS: MSC from both sources
      produced tissue with cartilage-like morphology that stained positive for
      proteoglycans and expressed cartilage markers. The CB-MSC pellets were larger and
      showed hyaline-like cartilage morphology as early as day six. Gene expression of
      collagen type 21, aggrecan and CD-RAP was higher in CB- than BM-MSC pellets.
      Expression of Sox9 mRNA was similar between CB- and BM-MSC pellets. Protein
      concentration of cartilage-derived retinoic acid sensitive protein was higher in
      culture medium from CB- than BM-MSC pellets. CONCLUSION: CB-MSC and BM-MSC were
      both capable of producing hyaline-like cartilage in vitro . However, in this
      study the MSC from umbilical cord blood appeared to have more chondrogenic
      potential than the BM-MSC based on the cells tested and parameters measured.

PMID- 19750291
TI  - Foreign body induced neuritis masquerading as a canine brachial plexus nerve
      sheath tumour.
AB  - A variety of clinical disorders caused by the foreign body reaction to migrating
      plant material have been reported in the dog. In this report, we describe a novel
      presentation in an adult dog in which this condition produced signs of
      progressive thoracic limb lameness and cervical spinal pain, mimicking a tumour
      of the brachial plexus.

PMID- 19750292
TI  - Evidence-based orthopaedics or 'superstition in the pigeon'.
AB  - Pigeon behavioural conditioning methods are similar to the processes that
      orthopaedic surgeons use to evaluate new surgical procedures. Alternatively,
      evidence-based orthopaedics is a tool for surgeons to evaluate procedures in a
      systematic, patient-centred way that is less instinctive than pigeon behaviour.
      The objective of this article is to describe evidence-based orthopaedics, and
      then propose changes to surgical culture with the aim of refining the
      interpretation of the current literature and improving the quality of future
      research. The proposals are 'institutional' changes rather than calls for
      increased funding and more randomised controlled trials.

PMID- 19750293
TI  - Vacuum-assisted wound closure following urine-induced skin and thigh muscle
      necrosis in a cat.
AB  - Vacuum-assisted closure (VAC) is a relatively new technique for wound management
      in dogs and cats. It was successfully used in this cat to treat severe urine
      induced skin and thigh muscle necrosis, resulting from a traumatic urethral
      rupture. No complications were encountered with application of the VAC technique
      and production of a healthy granulation bed, suitable for wound reconstruction,
      was achieved after only five days of VAC treatment. The marked wound contraction
      (40.3%) obtained after eight days of treatment, was sufficient to allow closure
      of the defect using a simple, rotational subdermal plexus flap. This was a safe,
      effective and efficient treatment for a challenging wound in a difficult
      anatomical location.

PMID- 19750294
TI  - Anatomical investigation of the canine cranial tibial artery.
AB  - OBJECTIVE: To investigate arterial vascularity at the level of the proximal tibia
      as a potential source of the severe intra-operative haemorrhage, which has been
      previously reported as a complication during tibial plateau levelling osteotomy
      (TPLO) and triple tibial osteotomy (TTO) surgeries in dogs. To devise a surgical
      approach for the management of this complication. METHOD: Eight pelvic limbs from
      five canine cadavers were dissected and the vascular structures at the level of
      the proximal tibia were identified and photographed. An arterial phase angiogram
      was performed on a sixth cadaver to further describe the vasculature in situ .
      Additional dissection was performed on four pelvic limbs to devise a medial
      surgical approach to the popliteal artery and the cranial tibial artery proximal
      to the stifle. RESULTS: The cranial tibial artery was identified as the most
      likely source of profuse haemorrhaging if damaged during proximal tibial
      osteotomy. Its course and branching are described. A simple medial approach to
      the popliteal artery at the level of its bifurcation into the cranial and caudal
      tibial arteries was developed. CLINICAL RELEVANCE: Understanding of the vascular
      anatomy at the level of the proximal tibia may prevent iatrogenic damage and
      resulting haemorrhage during TPLO and TTO surgeries. Temporary occlusion of the
      cranial tibial artery can be achieved through a simple medial approach, proximal
      to the stifle, in the event of severe haemorrhage associated with TPLO or TTO.

PMID- 19750295
TI  - [The elderly and the drug regimens complexity].

PMID- 19750296
TI  - [Why review answer criteria in solid tumors ?].

PMID- 19750297
TI  - [Botulinum toxin or lateral sphincterotomy for the treatment of chronic anal
      fissure?].

PMID- 19750298
TI  - [Venous thromboembolism:prophylaxis in clinical patients. Part III. ].

PMID- 19750299
TI  - [Does the use of hormone therapy in postmenopausal women promote benefits? ].

PMID- 19750301
TI  - Leukoplakia of the anal verge with bleeding hemorrhoids: a case report.

PMID- 19750302
TI  - Neonatally-induced diabetes: lipid profile outcomes and oxidative stress status
      in adult rats.
AB  - BACKGROUND: Experimental models are developed for the purpose of enhancing the
      understanding of the pathophysiological mechanisms involved in diabetes.
      Experimental findings lead to the development of treatment strategies to maintain
      metabolic conditions as close to normal as possible. There are several reports
      about streptozotocin induced mild diabetes to reproduce type 2 diabetes. However,
      studies about the interaction among glucose levels, lipid profile, and oxidative
      stress in these animals remain insufficient. Therefore, this study evaluated
      these parameters in blood samples from adult Wistar rats treated neonatally with
      streptozotocin. METHODS: Female newborn Wistar rats received streptozotocin (70
      mg/kg, i.p.) on the 5th day of life (n5-STZ). Glycemia was measured in the 3rd
      and 4th month of life. At the end of the 4th month, blood samples were collected
      and processed for lipid profile and oxidative stress measurements. RESULTS:
      Glycemia of n5-STZ rats were significantly higher compared to those of control
      rats (p<0.05). There was no alteration in levels of total cholesterol,
      triglycerides, lipid peroxidation (TBARS), SOD activity and GSH-t determination
      (p>0.05) in the n5-STZ animals when compared to control group. However n5-STZ
      animals showed a significant decreased HDL-cholesterol rate (p<0.05). CONCLUSION:
      This streptozotocin-induced diabetes model in rats caused hyperglycemia (120-360
      mg/dL), characterizing mild diabetes. This glycemic level led to HDL-lipoprotein
      alteration, which was not sufficient to impair antioxidant enzyme activities or
      determination of lipid peroxidation in adult life of rats. Further this
      experimental investigation contributed to the understanding of different results
      found in other models for mild/moderate diabetes induction in laboratory animals
      as well as to a better comprehension of the pathophysiological mechanisms of mild
      diabetes or hyperglycemia in humans.

PMID- 19750303
TI  - [Malnutrition and inadequate food intake of patients in the waiting list for
      liver transplant].
AB  - OBJECTIVE: Nutritional status of patients in the waiting list for liver
      transplant must be assessed due to the many risk factors associated with
      nutritional deficiencies. This was the aim of the study. METHODS: Throughout a
      period of 13 months, patients on the waiting list for liver transplantation were
      nutritionally assessed by the Subjective Global Assessment (SGA) and food intake
      was assessed by using the 24 hour recall instrument. RESULTS: 159 patients were
      included, mean age 50.5 +10.6 years and 71.1% were men. Overall malnutrition
      according to SGA was 74.7%, with 28% of patients considered severely
      malnourished. Malnutrition was associated with Child-Pugh score, presence of
      ascites and/or edema, previous episodes of encephalopathy and use of three or
      more medications and lower levels of physical activity. Socio-economic aspects,
      etiology of the disease and MELD score did not affect the nutritional status (p =
      NS). Calorie needs were not reached by 90.7% of patients and 75.7% of them did
      not reach protein requirements. CONCLUSIONS: In conclusion, malnutrition is
      highly prevalent amongst patients on the waiting list for liver transplantation
      and most do not meet nutritional requirements which certainly contribute to the
      vicious cycle leading to a deranged nutritional status.

PMID- 19750304
TI  - [Neurofibromatosis type 1: more frequent and severe then usually thought].
AB  - OBJECTIVE: To study prevalence of clinical features among Brazilian patients
      diagnosed with neurofibromatosis type 1(NF1), comparing these features with
      international data to evaluate the severity and visibility of the disease and
      quantify less frequent manifestations such as short stature, macrocephaly, muscle
      strength, voice abnormalities and oral motor disorders. METHODS: 183 patients
      diagnosed with NF1, attended at the Neurofibromatosis Outpatient Reference
      Center, were evaluated for clinical manifestations and complications of NF1.
      Severity and visibility were verified using the Riccardi and Ablon scales
      respectively. Voice abnormalities and oral motor disorders were quantified using
      the Vox-Metria software and maximal voluntary muscle strength (MVMS) was
      quantified using a handgrip dynamometer. RESULTS: Clinical manifestations of NF1
      observed were comparable to those described in literature. However, more then 50%
      of patients presented severity and visibility classified as moderate and severe.
      The incidence of macrocephaly and short stature was higher among the Brazilian
      patients. Voice abnormalities and oral motor disorders were quantified for the
      first time, with hoarseness and oral motor disorders observed in more then 60%
      the patients. Maximal voluntary muscle strength was found to be reduced in 67% of
      patients. CONCLUSION: The main clinical features of these patients are similar to
      those reported in previous studies. More then one-half of the patients presented
      moderate and severe levels of NF1 (severity and visibility), including short
      stature, macrocephaly, voice abnormalities and oral motor disorders and decreased
      muscle strength. These results are in disagreement with the traditional concept
      that NF1 is a benign disease and also disclosed some clinical aspects not
      previously reported.

PMID- 19750305
TI  - [Ethics relevance in Brazilian medical journals].
AB  - OBJECTIVE: To evaluate the Brazilian journals cited by the four CAPES medical
      areas, qualified as 'A' national or 'I' international, regarding the relevance
      given to ethics in the instructions for authors. METHODS: The instructions for
      authors of twenty Brazilian journals were studied and 36 types of ethical
      concerns were identified allowing the following categorization: I - Ethics in
      human research; II - Scientific integrity; III - Editorial policy. RESULTS: The
      results on Category I show that the most frequent instructions (50%) requires
      previous approval of the research by a institutional Ethics Committee (CEP),
      followed by indication on how to cite this approval in the body of the article
      (35%), plus presentation of a copy of the CEP approval (30%). However, none
      advert on the importance of the CEP being recognized by the CONEP. On Category
      II, 55% of the journal require declarations of conflict of interest, and 40% of
      them inquire about the type of interest; however, all (100%) journal do not
      mention prevention conflict of interests between authors and peer reviewers,
      neither on frauds, plagiarisms or data fabrication. Finally, in Category III, 65%
      of the journals require the authors to transfer publications rights to them,
      while the remaining 35% do not mention copyright CONCLUSION: These results are
      discussed in relations to the Brazilian present situation regarding ethics in the
      scientific production of researches using human subjects for the prevention of
      scientific dishonesty.

PMID- 19750306
TI  - Effects on mother and fetus of epidural and combined spinal-epidural techniques
      for labor analgesia.
AB  - OBJECTIVE: Epidural (EA) and combined spinal-epidural (CSE) techniques have both
      been utilized for labor analgesia. This study compared the effects on the mother
      and newborn of these techniques in labor analgesia and anesthesia. METHODS: Forty
      pregnant women received epidural analgesia with 15 mL of 0.125% ropivacaine (EA
      group) and 5 microg of sufentanil plus 2.5mg bupivacaine in the subarachnoid
      space (CSE group). Pain intensity, sensory blockade level, latency time, motor
      block intensity, labor analgesia duration, epidural analgesia duration, maternal
      hypotension, and pruritus were evaluated. The newborns were evaluated by Apgar
      and the neurological and adaptive capacity score (NACS) developed by Amiel-Tison.
      RESULTS: There were no significant statistical differences between groups for
      pain scores, latency time, sensory blockade level, and Apgar score. Motor block,
      labor analgesia duration, and epidural analgesia duration were greater in the CSE
      group, whose seven mothers had mild pruritus. The NACS were greater in the EA
      group after half, two, and 24 hours. Ninety five percent of EA group newborns and
      60% of CSE group newborns were found to be neurologically healthy at the 24 hour
      examination. CONCLUSION: EA and CSE analgesia relieved maternal pain during
      obstetric analgesia, but CSE mothers had pruritus and a longer labor. Newborns of
      mothers who received epidural analgesia showed the best NACS.

PMID- 19750307
TI  - Cost-effectiveness of anastrozole, in comparison with tamoxifen, in the adjuvant
      treatment of early breast cancer in Brazil.
AB  - OBJECTIVE: Breast cancer, a leading type of cancer in many developing countries,
      is the most frequent non-cutaneous tumor in Brazil. Hormone therapy is the
      standard of care in the adjuvant treatment of early-stage, hormone-receptor
      positive disease, and both tamoxifen and third-generation aromatase inhibitors
      are options in postmenopausal women. The comparative cost-effectiveness of
      different treatment strategies is of considerable interest in societies facing
      limited resources. METHODS: In an attempt to compare cost-effectiveness of
      upfront treatment with tamoxifen or anastrozole, the medical and economic results
      in a hypothetical cohort of 64-year-old postmenopausal women, was analyzed
      considering the Brazilian healthcare system in 2005, the primary perspective of
      the private sector, and a lifetime horizon. Data from the ATAC Trial, Markov
      modeling, a modified Delphi panel, and microcosting (in Brazilian R$) were used
      to estimate costs and effectiveness of the two upfront strategies. RESULTS: The
      model estimated a gain of 0.55 discounted life-years for patients receiving
      anastrozole, relative to those treated with tamoxifen. With an incremental cost
      of R$ 15,141.15, the model estimated that the cost-effectiveness of anastrozole,
      in relation to tamoxifen, was R$ 27,326.80. Monte Carlo simulations showed that
      approximately 50% of the cases fell below the threshold of R$ 29,229.00 per life
      year gained, which is recommended by the World Health Organization for Brazil.
      CONCLUSION: It was concluded that upfront anastrozole is a cost-effective option
      compared with tamoxifen in the adjuvant treatment of postmenopausal women with
      hormone-receptor-positive early breast cancer.

PMID- 19750308
TI  - [Irritative bladder symptoms after vaginal delivery or c-section].
AB  - OBJECTIVE: This study intended to investigate the frequency of irritative bladder
      symptoms three years after delivery in women previously interviewed in the third
      trimester of pregnancy and its correlation to mode of delivery, parity, maternal
      age, birth weight, episiotomy and forceps. METHODS: From 340 women previously
      evaluated at the third trimester of pregnancy, 120 were interviewed three years
      after delivery, between June and October 2006. Correlation of postpartum
      irritative bladder symptoms and mode of delivery (exclusively vaginal or c
      section), parity, maternal age, birth weight, episiotomy and forceps was
      analyzed. Associations between irritative bladder symptoms and obstetric
      parameters were assessed by the Fisher's exact test and Chi-square (p< 0.05).
      RESULTS: The study group consisted of 37.5% primiparous and 62.5% multiparous
      women. Mode of delivery was exclusively vaginal in 53 women and exclusively c
      section in 42. No statistical difference was found between irritative bladder
      symptoms and mode of delivery and parity. No statistical difference was found
      between irritative symptoms and maternal age (> 35), birth weight (>or= 4000 g),
      episiotomy and forceps. CONCLUSION: After childbirth, dysfunction of the lower
      urinary tract, characterized by irritative bladder symptoms, was not associated
      with mode of delivery, parity, maternal age, birth weight, episiotomy and
      forceps.

PMID- 19750309
TI  - [Use of forced-air to prevent intraoperative hypothermia].
AB  - OBJECTIVE: Hypothermia is a life-threatening event during the perioperative
      period. No consensus has been reached about the best active warming approach for
      such cases. Furthermore there is no consensus on the most appropriate time to
      warm a hypothermic patient. This study aimed to assess the efficacy of a forced
      air blanket to warm patients at 38 degrees C before and during surgery. Following
      utilization of the forced-air blanket, adverse effects were evaluated. METHODS:
      Patients submitted to orthopedic surgeries were divided into four groups of 15
      patients. In the control group (Gcont), patients were not warmed with a forced
      air blanket. In the preoperative group (Gpre), intraoperative group (Gintra), and
      total group (Gtotal), patients were warmed at 38 degrees C, during 30 minutes
      before anesthetic induction, after anesthetic induction up to 120 minutes and
      before and after the induction, respectively. Parameters evaluated were central
      (tympanic) temperature, peripheral (skin) temperature, operating room
      temperature, variations in the hemodynamic conditions and warming-induced adverse
      effects. RESULTS: Only Gtotal did not show significant variation in central
      temperature. Central temperatures of Gtotal patients were significantly higher (p
      <0.05) than those of other groups at 60 and 120 min after induction. In Gcont,
      Gpre and Gintra, patients were hypothermic at 60 min. CONCLUSION: The forced-air
      blanket is effective to prevent intraoperative hypothermia when applied for a
      period ranging from 30 min before anesthetic induction to 120 min after
      anesthetic induction. In the conditions of this study, adverse effects were not
      observed.

PMID- 19750310
TI  - [Body contour surgery in the massive weight loss patient: three year-experience
      in a secondary public hospital].
AB  - OBJECTIVE: To present the clinical-surgical three year-experience related to body
      contour surgery in the massive weight loss patient, performed by the Plastic
      Surgery team of the Sapopemba State Hospital. METHODS: Retrospective study
      performed at the Sapopemba State Hospital, linked to the 'Hospital das Clinicas'
      of the University of Sao Paulo School of Medicine, from July 2005 to July 2008. A
      total of 98 patients was operated, whose morbid obesity had been treated by
      bariatric surgery, after success of the technique, or weight loss by non-surgical
      method. Exclusion criteria were smoking, gestational intent and weight
      instability. Stable weight for at least 6 months after satisfactory weight loss
      was required from patients. RESULTS: Of the 98 operated patients, 97% were
      female, with mean age of 40.5 years and the weight loss method was the surgery in
      88% of cases. From 177 plastic surgeries performed, 46% were abdominoplasty,
      followed by mammaplasty (15%), thigh suspension (13%) and brachioplasty (12%).
      Mean hospital stay was of two days and the main diagnosed complications were:
      seroma (28%), minor necrosis/dehiscences (18%), major necrosis/dehiscences (4%),
      hematomas (4%), superficial thrombophlebitis from the saphena vein (2%) and deep
      venous thrombosis (1%). CONCLUSION: An increasing demand for surgeries to improve
      body contour after massive weight loss has been detected. Plastic surgeons must
      know the clinical peculiarities and higher risk of complications of these
      patients, control their expectations, analyze results and engage in a continued
      investigation to improve surgical techniques.

PMID- 19750311
TI  - [APACHE II and ATN-ISS in acute renal failure (ARF) in intensive care unit (ICU)
      and non-ICU].
AB  - INTRODUCTION: Acute renal failure (ARF) remains highly prevalent with a high rate
      of morbidity and mortality. OBJECTIVE: of this study was to compare use of the
      APACHE II scoring prognosis with that of the ATN-ISS to determine whether the
      APACHE II could be used for patients with ARF outside the ICU. METHODS: For this
      purpose, 205 patients with ARF were accompanied in a prospective cohort.
      Demographic data, preexisting conditions, organ failure and characteristics of
      ARF were analyzed. The prognostic scores were performed with the assessment of a
      nephrologist. RESULTS: The mean age was 52 +/- 18 years, 50% were male, 69% were
      white, 45% were treated in ICU and 55% in other units. Mortality in the ICU group
      was 85% and in the non-ICU group 18%. Factors that correlated with higher
      mortality were more prevalent in the ICU group: age, male, hospitalization with
      ARF, organ failure, sepsis, septic IRA, oliguria and need of dialysis. Overall,
      the prognostic markers were the same for both the ICU and non-ICU groups. The
      discrimination with the APACHE II was similar in both, ICU and non-ICU groups and
      calibration was better in the non-ICU group. The ATN-ISS achieved good
      discrimination in both the ICU and non-ICU groups, but, regarding calibration,
      there was a discreet over estimating of mortality in the non-ICU group. The ATN
      ISS showed a greater capacity for discrimination than the APACHE II in both the
      ICU and non-ICU groups. CONCLUSION: It was concluded that the APACHE II and ATN
      ISS scores could be used for stratification of risk in patients with ARF treated
      outside of the ICU in Brazil.

PMID- 19750312
TI  - [22q11.2 deletion syndrome: importance of clinical evaluation and FISH analysis].
AB  - OBJECTIVE: The 22q11.2 deletion syndrome nowadays is considered one of the most
      often observed genetic diseases in humans. It is clinically characterized by a
      rather wide phenotypic spectrum, with more than 180 clinical features physical as
      well as behavioral, already described. However, none is pathognomonic or
      obligatory which makes diagnosis even more difficult. Thus, this study intended
      to determine the prevalence and clinical characteristics of patients with 22q11.2
      microdeletion in a selected sample of subjects with clinical suspicion of 22q11.2
      deletion syndrome and normal karyotype. METHODS: A selected sample of 30 patients
      with clinical suspicion of 22q11.2 deletion syndrome and normal karyotype was
      evaluated by application of a standard clinical protocol and cytogenetic analysis
      with fluorescent in situ hybridization. RESULTS: 22q11.2 microdeletion was
      identified in 3 patients (10%), a prevalence similar to the majority of published
      studies, which ranged from 4 to 21%. The 22q11.2 deletion syndrome patients in
      this study were characterized by a variable phenotype and shared few clinical
      features, in agreement with the literature description. CONCLUSIONS: These
      findings strengthen the idea that clinical diagnosis of 22q11.2 deletion syndrome
      is difficult due to the large phenotypic variability. Therefore a detailed
      clinical evaluation associated to a sensitive test such as fluorescent in situ
      hybridization analysis is crucial for the identification of these patients.

PMID- 19750313
TI  - [Socio demographic characterization and perinatal outcome of pregnancies with
      ultrasonographic diagnosis of major fetal malformation in a referral centre].
AB  - OBJECTIVE: The purpose of this study is to describe the socio demographic profile
      and perinatal outcome of pregnant women with prenatal ultrasound diagnosis of
      major fetal malformation at the Hospital das Clinicas, Medical School, Sao Paulo
      University. The study was performed from December 15th 2005 to December 15th
      2006. METHODS: This is an observational descriptive study where 335 pregnant
      women were interviewed after agreement. Postnatal information was obtained until
      a month after due date of birth. Cases that were not confirmed and did not
      consent to participate in the study were excluded. RESULTS: Mean maternal age was
      27.1 years and skin color was brown in 48.1% of cases. According to the education
      level and salary, 57.8% did not finish college and the mean monthly income was
      3.1 minimal wages. A previous history of fetal malformation was reported by 10.4%
      of women. The central nervous system was the most frequent site of malformation
      (28.1%), followed by renal (9.3%) and cardiac (9%) defects. Fetal karyotype
      results were abnormal in 23.6% of fetuses. Pregnancy outcome was ascertained in
      311 cases (92.8%): 76.8% were alive, 25.7% were neonatal deaths, 16.4% were
      stillborn and 6.3% miscarried. CONCLUSION: This study describes social
      demographic features and perinatal outcome in pregnancies with major fetal
      malformation diagnosed antenatally. This information is useful for parent
      counseling in cases with an abnormal fetal diagnosis.

PMID- 19750314
TI  - [The effect of vitamin A supplementation upon retinol concentration in the
      colostrum of women in a public maternity hospital].
AB  - OBJECTIVE: The aim was to evaluate the effect of supplementary vitamin A upon the
      colostrum retinol levels in puerperal women cared for at a public maternity
      hospital in Natal, RN, Brazil. Analysis was conducted on the influence of the
      colostrum retinol and the maternal nutritional condition as response to
      supplementation. METHODS: For analysis of serum retinol 5 ml of fasting blood and
      two samples of milk were collected before and 24 hours after supplementation. A
      questionnaire was used to define the frequency of previous vitamin A intake. High
      Efficiency Liquid Chromatography was used to analyze the retinol. RESULTS:
      Vitamin A intake was 1492.4 +/- 1264 microg RAE/day and 23% probably had an
      inadequate intake. At the beginning of supplementation, 0 hour, and at 24 hours,
      the control and supplemented groups presented serum retinol concentrations of 1.3
      +/- 0.4 and 1.4 +/- 0.4 micromol/L (7% deficiency) and 3.5 +/- 1.7 micromol/L and
      3.3 +/- 1.8 micromol/L (p>0.05) at 0 hour colostrum, respectively. Retinol in the
      24 hours milk of the supplemented group increased from of 3.6 +/- 1.9 and 6.8 +/-
      2.6 micromol/L (p<0.0001), respectively. Women with deficient levels of retinol
      in the colostrum at 0 hour(<2.04 mol/L) transferred more retinol to the colostrum
      at 24 hours milk than those with adequate levels (an increase of 326.1% and
      86.5%, respectively). CONCLUSION: The megadose of vitamin A was efficient in the
      first 24 hours after supplementation. The supplementation response was influenced
      by the basal levels of retinol in the colostrum. Parturient women with low
      initial levels of retinol transferred more retinol to the milk, after the
      megadose, than nursing women with sufficient levels. This possibly confirms the
      action of the Vitamin A transfer mechanisms proposed by the mammary gland.

PMID- 19750315
TI  - [The different perspectives in the assessment of learners during supervised
      clinical clerkship].
AB  - OBJECTIVE: To compare medical students' global itemized ratings (GIR) and real
      case structured clinical assessment (RC-SCA), generated by faculty members from
      three different specialties (Gynecology-O&G, Internal Medicine-IM, Pediatrics
      Ped). METHOD: 106 Y4 learners were assessed by one faculty member from each
      specialty, who filled in GIR, consisting of 6 technical domains (mean score GIRt)
      and 7 humanistic domains (mean score GIRh), on a 0-10 scale, and resultant RC
      SCA, from direct attendance observation. Statistical analyses used Cronbach
      coefficient, Friedman and Wilcoxon paired tests, Pearson and Spearman correlation
      coefficients, Euclidean distances. Significance level=5%. RESULTS: High internal
      consistency was observed in the three GIR (> 0.92). Ratings were negatively
      skewed. Ped scores were significantly lower than O&G and IM (median differences
      between 0.50 and 0.67), with low correlations between them (-0.02<R<0.48). the
      domains that had greater impact on the reliability of GIR were: clinical judgment
      (O&G and Ped), problem-solving (IM), and self-reflective skills (Ped). O&G and
      Ped scores showed the smallest agreement; GIRt Ped scores showed the greatest
      disagreement with all the other scores. CONCLUSION: The specialties have
      different views on how to evaluate students' skills, inspite of using similar
      instruments, which can be a reflection of their 'culture'. the challenge remains
      to minimize these differences through faculty development activities.

PMID- 19750316
TI  - [Fasting leptinemia in eutrophic children and adolescents].
AB  - OBJECTIVE: To determine, in a group of eutrophic children and adolescents, the
      values of fasting leptinemia and its correlation with age and body mass index.
      METHODS: A cross-sectional study conducted in two public schools in Ribeirao
      Preto, Brazil. Anthropometric measurements and venous blood samples were obtained
      for determination of fasting leptinemia of 448 eutrophic and medium mature
      children and adolescents, of both genders, aged between 7 and 17.9 years. Using
      the Mann-Whitney test, comparisons were made between the concentrations obtained
      for boys and girls in each age group. Subsequently, using the Kruskal-Wallis
      test, values were compared in each age group and, using the Spearman correlation
      test, the correlations between fasting leptinemia and age and between fasting
      leptinemia and the z-scores of body mass index were assessed. RESULTS: Fasting
      leptinemia values differed between boys and girls in all age groups and it was
      higher for girls. Among boys, the values of leptinemia did not show statistically
      significant variation; among girls, there was variability, with gradual increase
      according to age group. The correlation study showed positive correlation between
      leptinemia and z-scores of body mass index in both genders and between leptinemia
      and age only for girls. CONCLUSION: The data show the necessity of establishing
      reference curves for fasting leptinemia taking into account gender age and body
      mass index.

PMID- 19750317
TI  - [Complexity of therapeutic regimens prescribed for elderly retirees, Belo
      Horizonte/MG, Brazil].
AB  - OBJECTIVE: To examine factors associated with therapeutic regimen complexity of
      drug prescriptions for elderly people in Belo Horizonte, Minas Gerais, Brazil.
      METHODS: A household survey of elderly people selected by simple random sampling
      from Brazil's social security register. The medication complexity index (MCI), a
      direct measurement of actions required to administer medication, was derived from
      information in the latest prescription. Univariate and bivariate analyses were
      performed to identify factors associated with the MCI. RESULTS: Of the 667
      interviewees, 56.5% had prescriptions meeting the inclusion criteria; most
      (69.2%) were females aged 72.4 years (mean); 35.5% self-rated their health good
      or very good; and 37.4% reported five or more diseases. In the 15 days prior to
      interview, 1873 drugs were used (mean=5.1), of which 942 appeared on the
      prescriptions examined (mean=2.5). Over the same period, 22.3% of interviewees
      failed to use some prescribed drug. The MCI ranged from 1 to 24 (mean=6.1).
      Number of drugs prescribed (>2), less schooling, worse perception of health and a
      lower benefit payment associated positively with greater complexity (p<0.05). An
      association was observed between regimen complexity and failure to use some drug
      in the preceding 15 days (p=0.034). CONCLUSION: Elderly people in worse socio
      economic and health conditions seem more likely to receive more complex
      therapeutic regimens, which are associated with non-compliance to the proposed
      treatment. This is an important consideration in the healthcare of elderly.
      Simplification of therapy could aid self-care among the elderly.

PMID- 19750318
TI  - [Hyperglycemia, morbidity and mortality in critically ill children: critical
      analysis based on a systematic review].
AB  - OBJECTIVE: This article focused on verifying if hyperglycemia in critically ill
      pediatric patients is a risk factor for increased morbidity and mortality and
      carried out a critical analysis of the articles in pediatrics and neonatology.
      METHODS: A systematic review of literature was performed using Medline, Cochrane,
      Lilacs and Embase databases and references of articles. Articles written in
      Portuguese, English and Spanish were selected and the terms used in the search
      were hyperglycemia, intensive care units (pediatrics), hospitals, pediatrics and
      pediatric intensive care. Cohort studies, retrospective and prospective, were
      selected for analysis. The outcomes evaluated were mortality during pediatric
      intensive care unit (PICU) stay, mortality during hospital stay, length-of-stay
      in the PICU, mortality due to specific diseases, and risk of infection and time
      of mechanical ventilation. RESULTS: During the study period 79 articles related
      to hyperglycemia in critically ill pediatric patients were selected; 15 (19%)
      were cohort studies (2 prospective and 13 retrospective) that were analyzed
      separately. CONCLUSION: Analysis of these cohort studies supported the conclusion
      that hyperglycemia, isolated or persistent during stay in PICU, increases
      morbidity, mortality and length-of-stay in PICU of critically ill children.
      However, these studies disclosed methodological issues such as lack of protocols
      for glucose measurement, design (most of them retrospective cohorts) and many
      articles did not confirm hyperglycemia as a single predictor of morbidity and
      mortality in pediatrics; therefore further prospective studies are necessary.

PMID- 19750319
TI  - Neuropsychological tests and driving in dementia: a review of the recent
      literature.
AB  - INTRODUCTION: Neuropsychological tests measure several aspects of cognition and
      are useful to evaluate elderly drivers with cognitive impairment. However, there
      is no consensus on a standard battery of tests that could accurately predict safe
      driving. OBJECTIVE: The aim of this study is to review specific
      neuropsychological measures that may be useful to predict driving competence of
      demented individuals. METHOD: To address neuropsychological tests used for
      dementia and the ability to drive, the authors searched for the keywords
      dementia, Alzheimer's, drive, driver, drivers, driving, tests,
      neuropsychological, and assessment, in Medline, PubMed, ISI and SciELO databases
      seeking articles from 2000 to 2008. RESULTS: From 131 articles, 27 met the
      inclusion criteria. Porteus Maze, Clock drawing, Trail B, UFOV and NAB Tests were
      found to be the most relevant neuropsychological measures for the evaluation of
      fitness to drive. CONCLUSION: Porteus Maze, Clock Drawing, Trail B, UFOV and NAB
      tests highlight visuospatial attention demands and/ or executive function. Those
      and other visuospatial and executive measures may be useful to predict driving
      competence of demented individuals.

PMID- 19750320
TI  - [Ascite--state of the art based on evidences].
AB  - The accumulation of free fluid of pathological origin in the peritoneal cavity is
      named ascites, and, in clinical practice this phenomenon is present in several
      diseases. The most common cause of ascites is liver cirrhosis. In the
      pathophysiology of ascites three theories are noteworthy: vasodilation, overflow
      and underfill. The modern concept suggest that these three theories are present
      in the same patient with cirrhosis depending on the disease evolution time. The
      vasodilation theory would be important in the pre-ascitic phase as well as during
      all the ascites evolution time. The overflow theory would be important in the
      first months of development of ascites in cirrhosis, and the underfill theory
      would explain most of the findings in patients with ascites for a long time. This
      article comments in detailed, several diseases that produce ascites, the
      diagnostic methods employed in clinical investigation of ascites' complication
      and therapeutics options available. In each item the evidence grade (A to C)
      found in medical literature is shown.

PMID- 19750322
TI  - The importance of genetic studies of lung cancer.

PMID- 19750323
TI  - Hospitalizations for asthma: impact of a program for the control of asthma and
      allergic rhinitis in Feira de Santana, Brazil.
AB  - OBJECTIVE: To evaluate the impact of the Programa de Controle da Asma e Rinite
      Alergica em Feira de Santana (ProAR-FS, Program for the Control of Asthma and
      Allergic Rhinitis in Feira de Santana) on the frequency of hospitalizations for
      asthma in patients monitored at a referral center for one year. METHODS: This was
      a historical control study involving 253 consecutive patients with asthma, ages
      ranging from 4 to 76 years. We compared the frequency of hospital admissions and
      visits to the emergency room (ER) in the 12 months prior to and after their
      admission to the ProAR-FS. During the program, patients received free treatment,
      including inhaled medications and education on asthma. Demographic and
      socioeconomic aspects were also assessed. RESULTS: There was a significant
      reduction in the number of hospitalizations (465 vs. 21) and of visits to the ER
      (2,473 vs. 184) after their admission to ProAR-FS (p < 0.001 for both). Of the
      253 patients who had been hospitalized and had had ER visits within the year
      prior to the admission to ProAR-FS, only 16 were hospitalized and 92 visited the
      ER during the follow-up year, representing a reduction of 94% and 64%,
      respectively. CONCLUSIONS: Implementing a referral center for the treatment of
      asthma and rhinitis in the Unified Health Care System, with the free distribution
      of inhaled corticosteroids and the support of an education program, is a highly
      effective strategy for the control of asthma.

PMID- 19750324
TI  - Influence of respiratory function parameters on the quality of life of COPD
      patients.
AB  - OBJECTIVE: To determine the quality of life of COPD patients by using the Medical
      Outcomes 36-item Short-Form Survey (SF-36) and the Saint George's Respiratory
      Questionnaire (SGRQ), correlating the scores with respiratory function
      parameters. METHODS: This was a cross-sectional study involving 42 COPD patients.
      We used the SGRQ (a specific questionnaire) and the SF-36 (a general
      questionnaire), together with their component summaries, in order to determine
      the quality of life of these patients. The functional profile was assessed by
      means of spirometry, arterial blood gas analysis and the six-minute walk test.
      RESULTS: Of the 42 patients, 30 (71.4%) were male and 12 (28.6%) were female. The
      mean age of the patients was 65.4 +/- 8.0 years. The mean physical component
      summary and mean mental component summary scores were 37.05 +/- 11.19 and 45.61
      +/- 15.65, respectively. The physical component summary correlated significantly
      with FEV(1) in L/s (r = 0.38; p = 0.012). There was a correlation between the
      SGRQ total score and FEV(1) (r = -0.50; p < 0.01). The SGRQ activity domain
      showed negative correlations with all respiratory function parameters. The
      multiple regression analysis showed that only FEV(1) correlated significantly
      with the SGRQ total score, as well as with the activity domain score (r= -0.32; p
      = 0.04 and r = -0.34; p = 0.03, respectively). CONCLUSIONS: In COPD patients, a
      decline in FEV(1) is associated with poorer quality of life, as evaluated using
      the SGRQ.

PMID- 19750325
TI  - Portuguese-language version of the Chronic Respiratory Questionnaire: a validity
      and reproducibility study.
AB  - OBJECTIVE: To determine the validity and reproducibility of a Portuguese-language
      version of the Chronic Respiratory Questionnaire (CRQ) in patients with COPD.
      METHODS: A Portuguese-language version of the CRQ (provided by McMaster
      University, the holder of the questionnaire copyright) was applied to 50 patients
      with COPD (70 +/- 8 years of age; 32 males; FEV1 = 47 +/- 18% of predicted) on
      two occasions, one week apart. The CRQ has four domains (dyspnea, fatigue,
      emotional function, and mastery) and was applied as an interviewer-administered
      instrument. The Saint George's Respiratory Questionnaire (SGRQ), already
      validated for use in Brazil, was used as the criterion for validation. Spirometry
      and the six-minute walk test (6MWT) were performed to analyze the correlations
      with the CRQ scores. RESULTS: There were no significant CRQ test-retest
      differences (p > 0.05 for all domains). The test-retest intraclass correlation
      coefficient was 0.98, 0.97, 0.98 and 0.95 for the dyspnea, fatigue, emotional
      function and mastery domains, respectively. The Cronbach's alpha coefficient was
      0.91. The CRQ domains correlated significantly with the SGRQ domains (-0.30 < r <
      -0.67; p < 0.05). There were no significant correlations between spirometric
      variables and the CRQ domains or between the CRQ domains and the 6MWT, with the
      exception of the fatigue domain (r = 0.30; p = 0.04). CONCLUSIONS: The Portuguese
      language version of the CRQ proved to be reproducible and valid for use in
      Brazilian patients with COPD.

PMID- 19750326
TI  - Respiratory diseases morbidity and mortality among adults attending a tertiary
      hospital in Nigeria.
AB  - OBJECTIVE: To determine the morbidity and mortality related to respiratory
      diseases among adults attending a tertiary-care hospital in Nigeria. METHODS: We
      carried out a retrospective study of 183 adult patients (> 15 years of age),
      diagnosed with respiratory diseases between November of 2006 and October of 2008
      at the Federal Medical Centre in Ido-Ekiti, Nigeria. RESULTS: Of the 183 patients
      enrolled in the study, 78 (42.6%) were male and 105 (57.4%) were female, the
      male: female ratio being 1:1.4. Respiratory diseases were predominant in the 25
      44 year age bracket (37.2%) and lower socioeconomic class (81.4%). Pulmonary TB
      was the leading cause of morbidity (in 42.1%), followed by asthma (in 17.5%) and
      pneumonia (in 15.3%). Lung cancer was uncommon (in only 0.6%). Pulmonary TB was
      the leading cause of hospitalization for respiratory disease (in 32%). Pulmonary
      TB, asthma, pneumonia and pleural pathologies were more common in women, whereas
      COPD was more common in men. The most common comorbidity was HIV infection (in
      11.5%). The overall mean length of hospital stay was 14 days. Overall mortality
      was 8.7%; 50% of the deaths were attributed to pulmonary TB, 25% were attributed
      to pleural disease, 12.5% were attributed to pneumonia, and 6.25% were attributed
      to acute exacerbation of COPD. Mortality was higher in women and in the 25-44
      year age bracket. CONCLUSIONS: Pulmonary TB, asthma and pneumonia were the
      leading causes of respiratory disease-related morbidity. Pulmonary TB was the
      leading cause of respiratory disease-related mortality among the adult Nigerians
      evaluated. Therefore, these conditions should be given higher priority in patient
      care. In addition, antiretroviral therapy should be readily accessible and
      affordable to HIV-infected individuals.

PMID- 19750327
TI  - Spatial analysis of hospitalizations for pneumonia in the Vale do Paraiba region
      of Brazil.
AB  - OBJECTIVE: To identify spatial patterns in hospitalizations for pneumonia in
      infants under one year of age in the Vale do Paraiba region of Brazil. METHODS:
      This was an ecological exploratory study using a georeferencing technique based
      on data from the Information Technology Department of the Brazilian Unified
      Health Care System on the number of hospitalizations for pneumonia among infants
      under one year of age in the Vale do Paraiba region between 2004 and 2005. Based
      on the distribution of the rates of hospitalizations for pneumonia per 1,000 live
      births, thematic maps were created. Moran's spatial autocorrelation coefficient
      was estimated, and the cities with the highest rates were identified using box
      maps. RESULTS: During the study period, 2,227 infants under one year of age were
      hospitalized for pneumonia. Moran's coefficient was 0.37 (p = 0.02),
      demonstrating a spatial autocorrelation for these hospitalizations. Eight cities
      deserving special attention for future interventions were identified.
      CONCLUSIONS: The spatial analysis was successful in determining the spatial
      autocorrelation, as well as in identifying the cities in which an intervention is
      necessary regarding the number of hospitalizations for pneumonia in infants under
      one year of age.

PMID- 19750328
TI  - Stability of the animal model of oleic acid-induced acute lung injury.
AB  - OBJECTIVE: To evaluate the stability of hemodynamic, respiratory and gas exchange
      variables in an animal model of oleic acid-induced acute lung injury. METHODS:
      This was an experimental study involving 10 mongrel dogs. The variables were
      measured at baseline, as well as at 30, 60, 90 and 120 min after the
      administration of oleic acid. In order to analyze repeated measurements, linear
      and quadratic effects were tested. Mixed linear models with diversified variance
      and covariance structures were used, depending on the variable studied. RESULTS:
      We found that mean arterial blood pressure stabilized at 30 min, as did heart
      rate, pulmonary arterial pressure and pulmonary capillary pressure at 60 min.
      Respiratory rate, tidal volume, minute volume and respiratory work stabilized at
      30 min. Regarding gas exchange variables, PaO2, PaO2/FiO2 ratio and pulmonary
      shunt fraction stabilized at 30 min. The remaining variables maintained a
      continuous rise or fall. CONCLUSIONS: This oleic acid-induced acute lung injury
      model is stable for some of the variables tested, although stabilization occurs
      at different times. The respiratory and gas exchange variables stabilized at 30
      min, whereas the hemodynamic variables stabilized at 60 min.

PMID- 19750329
TI  - Polymorphism of the CYP1A1*2A gene and susceptibility to lung cancer in a
      Brazilian population.
AB  - OBJECTIVE: To estimate and compare the frequency of CYP1A1*2A gene polymorphisms
      in a Brazilian population and determine the possible contribution of these
      genetic variations to lung cancer risk. METHODS: The study population included
      200 patients with lung cancer, and the control group consisted of 264 blood
      donors. Genomic DNA was obtained from peripheral blood samples. The PCR-RFLP
      method was used for analysis of the CYP1A1*2A gene. RESULTS: There was no
      statistically significant difference between the lung cancer patients and the
      controls in terms of the distribution of CYP1A1*2A polymorphisms (p = 0.49). A
      multivariate logistic regression model analysis by ethnic group revealed that,
      within the lung cancer group, the CYP1A1*2A genotype CC plus TC was more common
      among the African-Brazilian patients than among the White patients (adjusted OR =
      3.19; 95% CI: 1.53-6.65). CONCLUSIONS: The CYP1A1*2A gene cannot be linked with
      lung cancer risk in Brazilian patients at this time. Larger epidemiologic studies
      are needed in order to establish whether the CC plus TC polymorphism increases
      the risk of lung cancer in African-Brazilians.

PMID- 19750330
TI  - Isoniazid-resistant Mycobacterium tuberculosis strains arising from mutations in
      two different regions of the katG gene.
AB  - OBJECTIVE: To analyze and compare the mutations in two different regions of the
      katG gene, which is responsible for isoniazid (INH) resistance. METHODS: We
      analyzed 97 multidrug-resistant Mycobacterium tuberculosis strains isolated in
      cultures of sputum samples obtained from the Professor Helio Fraga Referral
      Center, in Brasilia, Brazil. Another 6 INH-sensitive strains did not present
      mutations and were included as controls. We used PCR to amplify two regions of
      the katG gene (GenBank accession no. U06258)-region 1, (from codon 1 to codon
      119) and region 2 (from codon 267 to codon 504)-which were then sequenced in
      order to identify mutations. RESULTS: Seven strains were resistant to INH and did
      not contain mutations in either region. Thirty strains carried mutations in
      region 1, which was characterized by a high number of deletions, especially at
      codon 4 (24 strains). Region 2 carried 83 point mutations, especially at codon
      315, and there was a serine-to-threonine (AGC-to-ACC) substitution in 73 of those
      cases. The analysis of region 2 allowed INH resistance to be diagnosed in 81.4%
      of the strains. Nine strains had mutations exclusively in region 1, which allowed
      the proportion of INH-resistant strains identified to be increased to 90.6%.
      CONCLUSIONS: The number of mutations at codon 315 was high, which is consistent
      with cases described in Brazil and in other countries, and the analysis of region
      1 resulted in a 9.2% increase in the rate at which mutations were identified.

PMID- 19750331
TI  - Epidemiological profile of hospitalized patients with TB at a referral hospital
      in the city of Rio de Janeiro, Brazil.
AB  - OBJECTIVE: To determine the epidemiological profile of inpatients at a TB
      referral hospital. METHODS: This was a descriptive, retrospective study of the
      medical charts of patients with TB hospitalized at the Hospital Estadual Santa
      Maria (HESM), in the city of Rio de Janeiro, Brazil, between January of 2002 and
      December of 2003. Data were collected using a standardized form. RESULTS: Of the
      451 patients included in the study, 313 (69.4%) had been referred to the HESM
      from health care clinics, and 302 (67.0%) were male. Most of the patients were in
      the 30-59 year age bracket, 443 (98.2%) lived in the greater metropolitan region
      of Rio de Janeiro, and 298 (66.1%) lived in the city of Rio de Janeiro itself.
      The most common reason for hospitalization was poor health status (in 237,
      52.5%). The most common comorbidity was AIDS (in 137, 30.4%). The most common
      signs and symptoms at admission were weight loss, fever and productive cough.
      Sputum smear microscopy was positive in 122 (71.0%) of the patients presenting
      with productive cough at admission. Of the 212 patients being retreated, 156
      (73.6%) reported noncompliance with previous treatment. Regarding the outcome,
      273 (65.8%) of the patients were referred to municipal health care centers, 83
      (18.4%) died, 44 (9.8%) were cured, and 27 (6%) were discharged against medical
      advice. CONCLUSIONS: Providing hospitals specializing in TB is relevant for TB
      control, especially in metropolitan regions. In addition to taking biosafety
      measures, these hospitals must be prepared to treat patients with TB-related
      comorbidities and social problems. This study has resulted in improvements at the
      HESM.

PMID- 19750332
TI  - Experimental diabetes mellitus: oxidative stress and changes in lung structure.
AB  - Diabetes mellitus is an endocrine/metabolic disorder characterized by
      hyperglycemia. Its impact on the respiratory system is characterized by
      functional changes and alterations in gas exchange. The objective of this study
      was to evaluate the increase in oxidative stress and the potential damages to the
      lung structure in an experimental model of streptozotocin-induced diabetes. We
      conducted histological, biochemical and blood gas analyses in the lungs of
      diabetic rats. We concluded that the effects of experimental diabetes mellitus
      include oxidative stress, structural changes in the lung tissue and altered gas
      exchange.

PMID- 19750333
TI  - Chronic interstitial lung diseases in children.
AB  - Interstitial lung diseases (ILDs) in children constitute a heterogeneous group of
      rare diseases that have been described and classified according to experiences
      and research in adults. However, pediatric pulmonologists have observed that the
      clinical spectrum is broader in children than in adults, and that many of these
      disorders have different courses and treatment responses. In addition, probably
      due to the various stages of lung development and maturation, new clinical forms
      have been described, particularly in infants. This has broadened the
      classification of ILDs in this age bracket. The understanding that neither the
      usual definition nor the standard classification of these disorders entirely
      apply to children has prompted multicenter studies designed to increase knowledge
      of these disorders, as well as to standardize diagnostic and therapeutic
      strategies. We have reviewed the conceptualization of ILDs in children, taking
      into consideration the particularities of this group of patients when using the
      criteria for the classification of these diseases in adults. We have also made a
      historical review of several multicenter studies in order to further
      understanding of the problem. We have emphasized the differences in the clinical
      presentation, in an attempt to highlight knowledge of newly described entities in
      young children. We underscore the need to standardize management of laboratory
      and radiological routines, as well as of lung biopsy processing, taking such
      knowledge into account. It is important to bear in mind that, among the recently
      described disorders, genetic surfactant dysfunction, which is often classified as
      an idiopathic disease in adults, should be included in the differential diagnosis
      of ILDs.

PMID- 19750334
TI  - Systemic corticosteroids as first-line treatment in pulmonary hypertension
      associated with POEMS syndrome.
AB  - The POEMS syndrome is a rare plasma cell disease. Pulmonary hypertension is an
      infrequent respiratory complication of this syndrome and might be associated with
      increased levels of various cytokines, chemokines and growth factors as part of
      the inflammatory phenomena that involve the physiopathology of POEMS syndrome. We
      present the case of a 54-year-old woman diagnosed with POEMS syndrome and
      pulmonary hypertension, which were treated with corticosteroids as the first-line
      therapy. The patient presented with the classic symptoms of this syndrome:
      polyneuropathy (confirmed by electromyography), organomegaly, subclinical
      hypothyroidism and monoclonal gammopathy detected in urine, together with skin
      changes. Right heart catheterization revealed a mean pulmonary artery pressure of
      48 mmHg, a cardiac output of 4.1 L/min and pulmonary vascular resistance of 8.05
      Woods. The serum level of brain natriuretic peptide (BNP) was 150 pg/mL. No other
      underlying disease was found during the investigation. Prednisone (1 mg/kg for
      three months) was then initiated, with a dramatic improvement in the clinical and
      functional condition. Levels of thyroid hormones and urinary protein levels (as
      determined using electrophoresis) normalized. Mean pulmonary artery pressure
      decreased to 26 mmHg, cardiac output decreased to 3.8 L/min, and pulmonary
      vascular resistance decreased to 2.89 Woods. Serum levels of BNP dropped to 8
      pg/mL. Our findings suggest that corticosteroids could play a role as a first
      line treatment in pulmonary hypertension accompanied by POEMS syndrome. Due to
      the rarity of this presentation, a multicenter registry should be developed to
      allow the compilation of additional data to support this practice.

PMID- 19750335
TI  - Post-intubation tracheal injury: report of three cases and literature review.
AB  - Post-intubation tracheal injury is a rare and potentially fatal complication.
      Among the most common causes, cuff overinflation and repetitive attempts of
      orotracheal intubation in emergency situations are paramount. Diagnosis is based
      on clinical and radiological suspicion, confirmed by fiberoptic bronchoscopy.
      Both conservative and surgical management apply, and the decision-making process
      depends on the patient profile (comorbidities, respiratory stability),
      characteristics of the lesion (size and location) and the time elapsed between
      the occurrence of the injury and the diagnosis. We report the cases of three
      patients presenting tracheal laceration due to traumatic orotracheal intubation,
      two submitted to surgical treatment and one submitted to conservative treatment.

PMID- 19750336
TI  - Intimal sarcoma of the pulmonary artery: a differential diagnosis of chronic
      pulmonary thromboembolism.
AB  - Intimal sarcoma of the pulmonary artery is a rare and potentially lethal tumor,
      the diagnosis of which is difficult and therefore frequently delayed. The
      clinical signs and symptoms are nonspecific, often mimicking chronic pulmonary
      thromboembolism (CPTE). We report the case of a 45-year-old male under treatment
      for CPTE associated with pulmonary arterial hypertension and chronic cor
      pulmonale. There was no response to treatment with anticoagulants and sildenafil.
      We emphasize the difficulties in diagnosing intimal sarcoma of the pulmonary
      artery, the need to investigate this neoplasm in the differential diagnosis of
      CPTE and the systematic use of criteria for the appropriate prescription of new
      medications for pulmonary artery hypertension.

PMID- 19750337
TI  - Narghile smoking keeps researchers in Wonderland.

PMID- 19750338
TI  - [Family Health Program in Brazil: an incomplete agenda?].
AB  - The present article is a longitudinal analysis of the Brazilian experience with
      the Family Health Program (PSF) throughout its 12 years of implementation. The
      article starts with the fundamental purpose of such strategy which is the
      reorganization of Basic Health Care, contextualizing in the light of this unique
      and peculiar experience to the Brazilian Unified Health System (SUS). It
      highlights the progresses and challenges of the PSF, indicating urgent needs
      regarding technological incorporation, formation of labor force, establishment of
      new mechanisms as well as agreements on basic care funds and the direction of new
      strategies and technologies in the process of monitoring and evaluation. To
      conclude, the article shows the elements to foster a debate about such questions,
      which must be permanent and lucid in the perspective of building the Brazilian
      Unified Health System and the right to health.

PMID- 19750339
TI  - [Decision making process and evaluation in health: expanding the debate on the
      Family Health Program (PSF)].

PMID- 19750340
TI  - [Comments on the Family Health Strategy and the Brazilian Unified Health System
      (SUS), promoted by Sousa and Hamann's text].

PMID- 19750341
TI  - [Primary care at health construction].

PMID- 19750343
TI  - [Evaluation of the care to the pregnant woman's health in the context of the
      Family Health Program].
AB  - The importance of health systems and services evaluation has been evidenced in
      several discussions on policies for health and practices in services. Thus, this
      study was carried out to analyze the primary care to the pregnant women by the
      Family Health Program (PSF) in the municipality of Teixeiras, Minas Gerais State.
      According to the propositions by Donabedian (1990) who relates the dimensions of
      structure, process and result, a specific score system was used to analyze these
      dimensions and their respective attributes, classifying the program into the
      incipient, intermediate and advanced sceneries, if the following were obtained:
      from 0.0 to 33.3%, 33.4% to 66.6, 66.7, and 100.00%, respectively. In summary,
      such dimensions resulted into a intermediate scenery (52.2%) for PSF
      characterized by an attention to the fragmented pregnant woman's health, although
      presenting some progresses concerning the organization of attention toward this
      group. Although progresses in implantation of PSF, the scenario reveals the
      program still presents strong characteristic marks of the hegemonic model
      centered on procedures and biomedical attention.

PMID- 19750344
TI  - [The degree of implementation of the Family Health Program and social
      indicators].
AB  - This research analyzes the relationship between social indexes and the
      implementation level of the Family Health Program (PSF) in cities of Santa
      Catarina State, Brazil. The social indexes applied were: total population, human
      development index (HDI), per capita expenses with health and political party at
      local administration. Findings have shown a strong relationship between the
      population number and the implementation of the PSF in the cities, with a higher
      number of smaller cities (up to 50,000 inhabitants) presenting a satisfactory or
      intermediate implementation level (p=0.0006). On the other hand, populous cities
      have presented a condition which is considered unsatisfactory for the PSF
      implementation. The HDI helped to detect a reverse correlation among the
      investigated factors (p=0.0264). This may be explained by the fact that the
      implementation has been put into practice mainly in small cities with scant aid
      resources. No correlation has been observed among the PSF implementation, the per
      capita expenses with health and the political group at local administration,
      suggesting that the isolated assessment of these indexes is not enough to
      understand the development of the public policies of the cities. Lastly, one may
      infer that local characteristics of the cities in which the program is
      implemented can interfere with the results, suggesting that changes and
      adaptations at city level are necessary to reach an adequate program
      implementation.

PMID- 19750345
TI  - [The insertion of oral health services in the Family Health Program at Minas
      Gerais State, Brazil].
AB  - The objective of this study was to analyze the administrative and operational
      aspects of Oral Health Teams (OHT) at the Family Health Program (FHP) in Minas
      Gerais State, Brazil. Two types of questionnaire were sent to 310 cities, and
      53.5% were answered until June/2004. From the total of the respondents, 66.9%
      reported unstable forms of hiring and 82.5% of the dental surgeons receive wage 9
      times lower than minimum wage for full-time job (8 hours); 75.9% of the cities
      presented an average of 4000 inhabitants for OHT. In average, 79.6% of all OHTs
      attended all ages group; 48.9% of dental surgeons reported not having
      participated in any of the courses offered. The integration between OH and FHP
      teams could be seen in 76.2 %, however only 54% organize regular meetings. The
      positive points observed were that FHP teams follow the principle of
      universality, the eight-hour shift and the quantitative extension allowing a
      higher access to oral health services. As negative points, it was observed the
      lack of qualification of the OHT, the excessive demand, the precarious work
      relations and the lack of involvement between OH and FH teams.

PMID- 19750346
TI  - [Characteristics of Family Health Program users sample in Campo Bom (RS), Brazil
      during the year of 2006].
AB  - This study aims to describe the characteristics of Family Health Program (FHP)
      users sample in a Basic Health Unit (BHU) in Campo Bom, southern of Brazil. Based
      on data collected from the handbook of the first 200 patients attended in a
      specific BHU in January 2006, we analyzed sex, age, average number of medical and
      nursing consultations in the last twelve months and the reasons for requiring a
      BHU attendance. In this sample, 68% were female. Children represented 30.5% of
      the sample and 35.5% of the patients self-declared as married. In addition to
      that, 59% had not finished basic school. Almost half (42%) of the citizens
      presented some chronic disease as a complaint to go to a BUH and 17% were looking
      for preventive health care. In 2005, 17% of the sample had, at least, one nursing
      consulting and 46.5% of these had from one to four medical consultations.
      Chronicle diseases and its symptoms or complications represented a significant
      percentage of the sample and might be associated to the demands for BHU health
      assistance. Data collected shows the necessity of more investments to prevent
      complications and/or incapability. Based on a deep understanding of BHU patients'
      profile, family health teams can improve effectiveness of their health promotion
      actions focusing on community demands.

PMID- 19750347
TI  - [New meanings for the psychologist practice in the Family Health Program].
AB  - This paper aims to analyze some of the definitions associated with the
      psychologist's practice at the Family Health Program (FHP). To do so, it was
      developed a qualitative research using the content analysis method to work with
      the data collected from a semi-structured interview with 07 volunteer
      psychologists, from July to August of 2006, who work in specifics FHP in Santa
      Maria, central region of Rio Grande do Sul state, Brazil. Some themes were
      selected and classified into two major categories: (1) identification/practice
      and education model of the psychologist; (2) new directions for the psychology
      practice in the FHP. According to the interviews, there is still the predominance
      of the clinical model in the psychology practice, with the support of the
      academic model of education, which results in some difficulties and adaptations.
      It is proposed, therefore, to discuss new directions for the psychology practice
      in primary health care as well as to indicate some suggestions for a possible
      change in the predominant model of health attention and in psychology practice.

PMID- 19750348
TI  - [Knowledge about tuberculosis by doctors and nurses, who work in the Family
      Health Strategy in the city of Vitoria, Espirito Santo State: a cross-sectional
      study].
AB  - Brazil is in 14th among the 23 countries responsible for 80% of the tuberculosis
      (TB) cases in the world. Aiming to understand the maintenance of these indexes,
      this study was developed to identify if the knowledge about tuberculosis by
      doctors and nurses, who work in the Family Health Strategy in the city of Vitoria
      (ES), would be a factor in the mediation of the prevention processes, diagnosis
      and treatment of the Tuberculosis. This is a cross-sectional study, with a sample
      size of 50 professionals. The collected data had been analyzed using the Chi
      square and Fisher Exact tests with significance level of 0.05. Regarding the
      transmission and diagnosis of the Tuberculosis, there was no statistically
      significant difference between doctors and nurses. Only one variable presented a
      statistical difference: 41% of doctors and 15% of the nurses (p<0.05) mentioned
      that the patient must be attended in a place of choice of the doctor or nurse,
      and still, 4% of the total of the sample had answered that the supervision cannot
      be made by a member of the family. The research proves that doctors and nurses
      has knowledge to reduce the indexes of Tuberculosis, even so is indispensable the
      continuous study and qualification of these professionals.

PMID- 19750349
TI  - ['Family health' multiprofessional teams: a reflection on the physiotherapist's
      role].
AB  - This article is intended to contribute for the debate instituted about the
      composition of 'Family Health' teams. It must be understood as a reflection about
      the possibility of integrating the physiotherapist to those teams, aiming to
      present some aspects of the profession that might potentially improve the
      outcomes of primary health care. On this study, we analyze the legal documents
      that approve the rules for qualifying professional physiotherapists. In the 1970s
      and 1980s, following Brazilian sanitary reform, those documents made official the
      process that led physiotherapy, which was historically recognized for its clinic
      acting, into a shift on its work object. This change approximated
      physiotherapists to preventive and health promotion practices, typical of the
      first level of care. We conclude that such changes opened an important space for
      integration still little explored. We propose to strengthen these new fields, by
      focusing the reflection on integration forms and on the necessity to impose to
      managers to plan their actions in association with the community, taking into
      account the local health situation and assuring intervention on problems
      according to priority population groups.

PMID- 19750350
TI  - [Nurse's daily reception in Family Health Units in Londrina, Parana State].
AB  - This paper analyses the auxiliary nurses' perception on the work of the Family
      Health team regarding users' receptiveness as a technology in the relationship
      with patients and community in Londrina, Parana State, Brazil. It is a
      qualitative research, which data was collected during a focal group. Thematic
      analysis of the content was performed for data analysis. Results show that
      auxiliary nurses have sensibility, are committed, and feel responsible for users'
      receptiveness, and recognize the importance of an integral and effective
      attention. They report knowing better the reality of the families' lives since
      the implementation of the Family Health Program, but highlight the fact that not
      all of them perform activities outside the unit. Contradictions have also been
      noted regarding the patients' rights provided by the Unified Health System,
      mainly about the universality of access. One of the reported difficulties was the
      increase of demand after the implementation of the Family Health Program. This
      situation presents itself as a challenge to change the attention model, and it is
      necessary to reorganize the process of work as well as to incorporate other
      fields of knowledge in order to promote the practice of receptiveness, and the
      integration of intra and extra activities at the unit.

PMID- 19750351
TI  - [Working in multiprofessional teams: the perspectives of family health
      residents].
AB  - Brazilian medical residency is increasingly specializing physicians in his
      practices undervaluing the multiprofessional practices that guide the integrality
      in health. Aiming at changing this practice, the multiprofessional residency in
      family health was proposed to prepare professionals searching for a comprehensive
      health care to the general public. In this context, in 2003, Faculdade de
      Medicina de Marilia started this residency program having as the main idea the
      multiprofessional work in family health teams. The study shows the perception of
      family health residents at Faculdade de Medicina de Marilia regarding the
      multiprofessional work developed in the Family Health Program. The method used in
      this research was the qualitative approach. The collected data had been
      interpreted through a thematic content analysis, building three empirical
      categories: Anchors and markers of an interdisciplinary view on team work that
      permeate the Family Health residency perspective; Conflicts and paradoxes of team
      work and the maintenance of an assembly line; Dilemmas of the team work facing an
      hierarchical structure. The data analysis points to an advancement that
      multiprofessional team work brings to the medical formation, once it allows
      perspectives that would not be possible without a team.

PMID- 19750352
TI  - [Psychology and basic attention: experiences of trainees in Family Health
      Strategy].
AB  - This study shows a qualitative research based on a humanist theory in relation to
      the experiences of trainees from the psychology course of PUC-Campinas, that are
      participating in family health teams in the areas of Health/Clinic and basic
      attention in public health. The participants were six trainees in the last year
      of the course and located in two Health-School Centers in the Northwest region of
      Campinas. The methodology used was an ethnographic view. The processes of data
      composition were produced in two different moments: a) by weekly register on the
      trainee's personal diary during five months; b) semi-directed individual
      interviews at the end of the term. These data were analyzed according to a
      phenomenological reading. It was found evolutive stages in the process of the
      trainee formation. Initially, the experience was lived with surprise and
      strangeness, resulting in contradictory feelings of innapropriation to their
      inexperience to work in teams. On the other hand, because they were well received
      by the group, there was a personal transformation considered to be very
      enriching, symbolized as a single felling of belonging, motivating efforts to a
      creative and integrating clinic practice.

PMID- 19750353
TI  - [Family health: changing practices? A case study in the city of Natal (RN),
      Brazil].
AB  - This article presents a qualitative case study where the unit of analysis was the
      Family Health Program team of Natal city, Rio Grande do Norte State, Brazil. The
      objectives were to analyze the conceptualizations of the professionals regarding
      teamwork as well as to identify in these practices the elements that contribute
      to an effective change in the hegemonic health model. The study was based on the
      Peduzzi (1998) typology and definition of health team and was conducted in six
      family health units in the North and East health districts selected by a pre
      established criteria. Data were collected using a semi-structured interview
      applied in family health teams, which were analyzed using the Collective Subject
      Discourse proposed by Lefevre and Lefevre (2003). The results indicate a
      predominance of an integrated team type, and also that teamwork is an essential
      element for the development of the Family Health Strategy.

PMID- 19750354
TI  - [Health educational praxis of the male nurses of the Family Health Strategy].
AB  - This study has a qualitative character and aims to analyze the educational praxis
      of male nurses of the Family Health Strategy in the city of Sobral, Ceara,
      Brazil. The data was collected using semi-structured interviews applied to 16
      male nurses, besides the observation of this group. All data was organized using
      the collective subject discourse technique. The dialectic hermeneutic was adopted
      as a theoretical-methodological referential. We conclude that, in a hegemonic
      way, the educational processes in health are graded in a behaviorist approach,
      eminently preventive, in which strategies and resources favor the
      unidirectionality and non-dialogical of the process. In spite of that, we
      identified a critical-reflexive movement among male nurses, in the sense of
      questioning the way of how the educational processes are developed. Anti
      hegemonic actions were also evidenced, like the use of educational methods graded
      in the community's needs and real problems, in which the subjects of approach are
      built in a horizontal way and in partnership with the community. Thus, the
      findings of this study show a tension between two educational models: the
      traditional and the dialogical.

PMID- 19750355
TI  - [Challenges to an interdisciplinary action in basic care: implications related to
      composition of family health teams].
AB  - The Family Health Program emerges as a new strategy of health care as well as a
      reorientation of the assistance model. Based on these presuppositions, this
      article reflects on the relationship between integrality in basic care and the
      composition of family health teams, in the view of the Family Health Program
      minimum team members, characterizing the possible fields of action and the
      contributions of other health professionals in the Family Health Program.
      Undergraduates and members of a Family Health Program team from a certain city in
      the south of Brazil participated in this research. The quality of personal or
      professional expertise of these professionals contributed to a better
      understanding of their intervention possibilities. The investigation also allowed
      the analysis of how the family health strategy has been reaching the members who
      constitute the minimum teams at local context. In addition to that, the research
      highlighted how the integrality and interdisciplinarity have been understood by
      the teams members, and the relationships between team arrangement and the
      (im)possibilities of action.

PMID- 19750356
TI  - [Evaluation of the impact of the Family Health Program in the epidemiology
      profile of the rural population of Airoes, city of Paula Candido (MG), 1992
      2003].
AB  - The Family Health Program (PSF) as a redirection strategy of the healthcare model
      of the country has promoted the substitution of assistential and cure model for
      the disease prevention and health promotion of individuals as well as the
      families and communities, placing the primary health care as the entrance to the
      healthcare system. This work aims to evaluate the PSF impacting in the rural
      community of Airoes, in the city of Paula Candido, Minas Gerais State, analyzing
      its contribution to the evolution of health indicators, since the comparison of
      sanitary data before and after implementation of the program, in the period
      ranging from 1992 to 2003. The information were obtained through a household
      survey applied to 127 families randomly selected within the community,
      representing 55.2% and 41.6% of the families in 1992 e 2003 respectively. After
      the PSF implementation there were a increase of 40.4% in diseases diagnosis and a
      reduction in the number of internment from 42.7% to 27.2%. Pre-natal assistance
      coverage was enlarged from 30.6% to 90% and the birth in homes reduced from 48.9%
      to 1%. Therefore, the evolution of the sanitary data in the community shows the
      characterization of the PSF as an effective strategy of implementation of the
      Unified Health System.

PMID- 19750357
TI  - [Partnership between Psychosocial Care Center and Family Health Program: the
      challenge of a new knowledge construction].
AB  - The objective of the article is to report an experience of partnership between a
      Psychosocial Care Center and three teams of the Family Health Program in the
      central region of Sao Paulo city. theoretical concepts like territory, subject,
      subjectivity/collective, receptiveness, bond, co-responsibility as well as the
      psychiatric and sanitary reform principles are the base and guide of this work.
      The partnership aims the promotion of mental health care based on articulated
      actions from different services. This way, the PSF's and mental health's workers
      are responsible for the demands of a territory. The strategies used in this
      partnership were meetings with both teams with training, case discussion about
      the families assisted, support to workers' difficulties and elaboration of
      therapeutical projects, and joint domiciliary visits. Some difficulties had been
      found during the research: great demand for health services and lack of
      institutional guidelines to guarantee the effectiveness of the partnership. The
      look directed to the family and the social context presents positive results
      compared to the look directed only to the illness. The partnership enriches the
      practice and a larger network of care in the territory becomes possible. It is
      necessary to bring up new proposals and innovative enterprises.

PMID- 19750358
TI  - [Family Health, more than never!].
AB  - The implementation of Primary Health Care as a strategy for organizing health
      care is undoubtedly important. There are already sufficient evidences that
      countries whose health systems are organized from the principles of Primary Care
      achieve better results on health with lower costs, higher level of user
      satisfaction and greater equity even in situations of great social inequity such
      as in Brazil. Strengthening Primary Care in Brazil has been a gradual process,
      showed with the expansion of the coverage of Family Health teams in all states of
      the federation, nowadays we have 29,148 of family health teams, 228,412 community
      health workers and 17,588 oral health teams working throughout the country. There
      are multiple studies on Family Health Strategy showing positive results that let
      no doubt about the success of this strategy. Despite all the advances, challenges
      were placed ahead, the most important are: the challenge of training and
      permanent education, the challenge of consolidating the PHC as system's
      coordinator and the challenge of communicating with society. We are on track,
      meet the challenges mentioned is an obligation of Brazilian society in the
      maintenance of greater social inclusion's policy, which is the Unified Health
      System driven by the primary care/Family Health Strategy.

PMID- 19750359
TI  - [Assisting users of a health care unit to stop smoking: an experience report].
AB  - Smoking is responsible for 4.9 millions of deaths every year, nationwide and
      worldwide. It is becoming a serious public health problem because of the damages
      caused to human health as regards its limitations to life quality, the incapacity
      to work, followed by illness and death. Most deaths occur in developing
      countries. Tobaccoism control strategies need to be intensified and improved,
      especially in low income areas. Herein is presented a experience report of
      tobaccoism control with cognitive behavior groups, at a health care unit in the
      suburbs of Porto Alegre, Rio Grande do Sul State. The inexpressive yearly number
      of people who quit smoking shows the great challenge to be faced. Therefore it is
      necessary the involvement of more professionals in such issue, mainly in the
      public health network.

PMID- 19750360
TI  - [Reflections around the performance of community health agents in oral health
      strategies].
AB  - The Community Health Agent (CHA) has traditionally been linked to doctors and
      nurses, being considered exclusive 'property' of these professionals.
      Historically, oral health tended to operate isolated, disconnecting the mouth
      from the rest of the body and the individual from his environment. The Family
      Health Program (FHP) points to important changes in the organization of services
      as well as in the work process. One of the differences is the teamwork joining
      different professionals, including oral health which was previously excluded. The
      objective of the study is to show the experience of the CHA qualifying course,
      which allowed the entrance of different professional categories into teaching.
      The course included three odontologists as lecturers, and CHA recognized other
      individuals as health team members, as well as expand the view of its role within
      oral health. The professors also had their practices modified, given that they
      could understand the often ignored suffering and limitations of the CHAs.

PMID- 19750361
TI  - [Health economic evaluation in a local level government health care system].
AB  - This work aims to contribute to the discussion about the possibility of applying
      health economic evaluations at local level government healthcare system, and
      consequently use the results of this study into decision making. In order to
      subside this reflexion, it was analyzed the SAMU/192 Program costs evaluation in
      the city of Belo Horizonte, as well as data concerning effectiveness of the
      program and a review on electronic databases (SciELO and Medline) about the
      application of studies in decision making. The analysis showed that even for a
      simple evaluation on expenditure, there are still unsolved problems of data
      availability as well as of data effectiveness on information systems definition
      and association. It showed that decision makers do not use the result of studies
      for decision making either. So, we conclude that there is no possibility to apply
      a health economic evaluation research and have the results used in a local level
      government health care system.

PMID- 19750362
TI  - [Technology of relations as device of humanized attendance in basic attention to
      health in the perspective of access, sheltering and attachment].
AB  - To health workers and users the technology of relations as a device of humanized
      attendance in basic attention, highlighting the categories access, sheltering and
      attachment can present diverse meanings and have a subjective nature to treat
      with each one of different interests of subjects involved in construction of
      health. Thus, the objective of this research is to discuss how users and workers
      notice the access, sheltering and attachment as soft technology in basic
      attention in city of Fortaleza, Ceara State. The research has a descriptive
      nature, focusing on qualitative analysis, having as theoretical basis the soft
      technology in attention to health. The data were collected in the context of
      twelve focal groups with 70 workers of Basic Units of Family Health and clinical
      interview with 30 users. To analyze the data, it was followed the technique of
      thematic categorical content. The results suggested that technologies of
      relations in actions of health indicate the need of respect, effective relations
      in work, resolutivity in attendance, access to information among staff members
      and among these and users.

PMID- 19750363
TI  - [Ethical relationship in Primary Health Care: the experience of medical
      students].
AB  - The ethical formation of doctors involves professional relationships that are
      part of their daily routine, and in this context, Faculdade de Medicina de
      Marilia (Famema) provides the medical students to live deeply since the beginning
      of the course at the Education Unit of Professional Practice, the ethical
      reflection of the actions in health when developing abilities in the Primary
      Health Care (PHC) together with the community. This scientific research analyzed
      the perception of academics of medicine on the first and second years concerning
      ethical actions in health developed together with the community. The qualitative
      approach was the option of analysis of this study that allowed the construction
      of three empirical categories common to the two years: The ethical and
      professional training in PHC's reality; Confidentiality of information on the
      development of medical professional secrecy; interpersonal relationships on
      ethical formation of medicine students, with more predominance of the second
      category among the first years students. Therefore, the ethical relations are
      more significant to the students when lived deeply, since the beginning in
      practices like these.

PMID- 19750364
TI  - [Management of health services: developed competencies and difficulties found in
      basic attention].
AB  - The objective of this article is to know the profile and check the competencies,
      management attributions and abilities in the level of structure of Basic
      Attention; to identify the difficulties and easiness in relation to their
      attributions and management of people. The research is a subject of study. A semi
      structured and a scale of Likert were used as the guide of research that was
      applied to the management of the basic units of health of Caxias do Sul, Rio
      Grande do Sul State, in November of 2006. It was evidenced that all managers have
      management skills that include communication, organization of tasks, planning of
      actions and negotiation. However, some described that the difficulty for the
      accomplishment of their attributions would be not having specific graduation in
      management. The problems in higher evidence were related to the bureaucracy
      excess, the overload of activities, the small physical area, the difficulties in
      manipulating and working with equipment as well as managing people. It has been
      noticed that there is a great need of computerizing the public system and enable
      professionals to work in programs, in order to accomplish the new assistance
      model and to recognize situations of social vulnerability and in health.

PMID- 19750365
TI  - [The users' view on the delivery of speech therapy in the Brazilian Unified
      Health System in Salvador (Bahia, Brazil)].
AB  - This article intends to analyze the supply of speech therapy services by the
      Brazilian Unified Health System in the city of Salvador. We have made thirty
      interviews with users at eight healthcare facilities, in differentiated shifts
      and we verified that the offer of speech therapy, in this city, is directed to
      medium and high complexity patients. There is a random and unequal distribution
      of services at sanitary districts. We have also noticed the multiple difficulties
      faced by users in accessing this treatment, which can be explained by the
      specialization of the offer, the network fragmentation and the deficit in speech
      therapy procedures, estimated in 131,315 per year. Therefore, regarding the
      concept of fair or bearable inequalities, and in order to reverse the inequities
      in the access to speech therapy, we suggest an urgent planning for this treatment
      in the three levels of attention.

PMID- 19750366
TI  - [Advances and challenges of the Unified Health System planning].
AB  - Since the Unified Health System creation, managers have been expending efforts to
      discuss the planning and, made attempts to institutionalize it, considering that
      it's a basic management component. However, despite advances obtained, there are
      aspects that are priorities and that constitute challenges for the
      institutionalization of the planning at the Unified Health System. In this
      direction, this study describes the planning evolution in the system, by legal
      and technician material analysis of published documents by Ministry of Health.
      From the planning conception in these publications, it leads a reflection on the
      used approach, considering the established management instruments, and its
      entailing to the more currently accepted theory and methodology of health
      planning. Aspects that need to be observed are pointed for the effectiveness to
      ascendant planning at the Unified Health System.

PMID- 19750367
TI  - [Education in health as a life quality promoter for elderly people].
AB  - This article presents considerations on the education in health as a life quality
      promoter in order to reach actions and behavior conditions for the Brazilian
      elderly community health. From a literature review, it could be noticed that the
      educational work has as challenge the integration of the huge knowledge in human
      and biological areas to the common knowledge, improving new policies in the model
      of the health care system. The education in health reveals to be the link between
      the desires and expectations of this population for a better life and the
      projections and policies of the government to offer more efficient health care
      programs.

PMID- 19750368
TI  - [Strategic health planning based on determinants: case of the municipality of
      Campo Bom, Rio Grande do Sul State. A methodological proposal for the
      decentralized management].
AB  - With the purpose to analyze the health strategic planning model based on
      determinants experienced in the municipality of Campo Bom, Rio Grande do Sul
      State, it was conducted an observational, qualitative study, of documental
      analysis as well as an evaluation of new process technologies in local health
      administration. This study contains an analysis of the methodological coherency
      and applicability of this model, based on the revision of the elaborated plans.
      The plans presented at Campo Bom case shows the possibility of integration and
      applicability at local level, of a health strategic planning model oriented to
      the new health concepts considering elements of different theoretical
      developments that enables the response to the most common local needs and
      situations. It was identified evolutional stages of health planning and analyzed
      integrative elements of the model and limitations of its application, pointing to
      the need of support the deepening on the study and the development of the field.

PMID- 19750369
TI  - [Senses and meanings of health socialized by cultural devices: readings of the
      warning images on cigarettes packs].
AB  - This article analyzes the images publicized on cigarettes packs that are part of
      the strategies from the Ministry of Health to combat the tabagism and available
      from the Cancer National Institute. These images bring the official speech of
      specialists and build narratives, understood such as truths, based on scientific
      knowledge. We have supported our thesis on theoretical referential of Cultural
      Studies, since its reflections help to understand that the subjectiveness is
      social and culturally built by different speeches and devices. We do not deny
      what is represented, but we establish dialogues with other possibilities of
      readings that can be present at these devices.We understand the propagated images
      as cultural pedagogies that behave as texts to be read, building up
      representations that can be assumed as true effect, and attributes to the citizen
      the necessity of constant control of its action. Reassuring the biomedicine and
      the health institutions, an onedimensional vision is propagated disregarding the
      complexity of this problem. We understand that the cultural pedagogies are part
      of competition territories, where the directions and meanings can be re-prepared
      producing hybrid identities that build up its own identity origins over this
      tangle of power relations.

PMID- 19750370
TI  - [Participation and integration: the self-organization theories point of view].
AB  - This article presents theoretical bases to facilitate participation and
      integration within an interdisciplinary research team. In order to achieve this,
      we will sketch fundamental notions related to the new conceptual field of self
      organization of living beings. Subsequently, we will expose some ideas by Henri
      Atlan, Jean-Pierre Dupuy and Cornelius Castoriadis that are important to reach
      our objectives. Finally, we will suggest how to turn these principles into
      practice.

PMID- 19750371
TI  - [Anencephaly: the magnitude of the judicial authorization among medical doctors
      in Brazil].
AB  - This paper describes the magnitude of the medical care for pregnant women with an
      anencephalic fetus. Anencephaly is an abnormality incompatible with life. The
      right to abort in this case is under litigation at the Brazilian Supreme Court.
      This survey was conducted among 1,814 medical doctors, all of them affiliated to
      the Brazilian Federation of Gynecology and Obstetrics (Febrasgo), corresponding
      to 12% of the doctors within this federation. The results show that, in a group
      of 9,730 women cared by the physicians over the last 20 years, 85% preferred to
      interrupt pregnancy in case of anencephaly. This fact reveals how common the
      experience of assist women pregnant with an anencephalic fetus is in health care
      services, as well as the ethical challenge imposed by the restrictive Brazilian
      legislation on abortion.

PMID- 19750374
TI  - Dietary transition and cultural diversity: challenges for indigenous health
      politics in Brazil.

PMID- 19750375
TI  - [Bioethics and nutrition in adult patients with cancer in palliative care].
AB  - Cancer constitutes a major group of chronic diseases and is the second leading
      cause of death in the developed countries. Palliative care proposes to offer
      comprehensive support to control symptoms and improve quality of life for
      patients and their families. Nutrition is an important tool in palliative care,
      helping patients with their physical, psychological, and social issues and
      promoting comfort and quality of life. However, in the context of palliative
      care, nutritional support rarely achieves its role of fully recovering and
      assuring nutritional status. At this point, the nutritionist must consider the
      individual patient's needs, preferences, and eating habits, which are essential
      both for controlling symptoms and assuring satisfaction and comfort. The
      impossibility of conventionally applying established management and the
      development of a new perception of the patient often raise dilemmas for
      professional nutritionists.

PMID- 19750376
TI  - [Cognitive function in menopausal women evaluated with the Mini-Mental State
      Examination and Word-List Memory Test].
AB  - There is little research in Brazil on cognition and menopause, despite the high
      frequency of neuropsychiatric complaints in this phase of women's life. The
      authors present a cross-sectional study aimed at describing the scores by 156
      menopausal women on the Mini-Mental State Examination (MMSE) and the Word-List
      Memory Test (WLMT). The mean score on the MMSE was 25.86 points (SD = 2.67),
      similar to other studies, except for better performance by illiterate women;
      scores on the sub-items 'attention and calculation' and 'immediate recall' showed
      lower values. In the WLMT, the mean was also consistent with the literature (M =
      18.83 words; SD = 3.82). The only significant associations with score were for
      schooling in both tests and arterial hypertension in the WLMT. The authors
      conclude that cognitive performance in these menopausal women is similar to that
      of other Brazilian samples, corroborating the wider range of scores among
      individuals with lower schooling. Complaints pertaining to memory in middle-aged
      women may be related to decreased attention.

PMID- 19750377
TI  - [Regular use of dental care services by adults: patterns of utilization and types
      of services].
AB  - The aim of this study was to estimate the prevalence of regular use of dental
      services by adults and identify groups where this behavior is more frequent. A
      cross-sectional population-based study was carried out in Pelotas, southern
      Brazil, including 2,961 individuals who answered a standardized questionnaire.
      Overall prevalence of regular use of dental services was 32.8%. The following
      variables were positively associated with regular use: female gender, age >or= 60
      years, no partner, high educational level, high economic status, private service
      user, good/excellent self-rated oral health, and no perceived need for dental
      treatment. Those who had received orientation on prevention and expressed a
      favorable view towards the dentist had higher odds of being regular users.
      Especially among lower-income individuals, regular use was infrequent (15%). When
      restricting the analysis to users of public dental services, schooling was still
      positively associated with the outcome. Dental services, especially in the public
      sector, should develop strategies to increase regular and preventive use.

PMID- 19750378
TI  - [Prevalence of respiratory symptoms and associated factors: a population-based
      study in adults from Lages, Santa Catarina State, Brazil].
AB  - A cross-sectional population-based study was conducted in Lages, Santa Catarina
      State, Brazil, in order to estimate the prevalence of symptoms of chronic
      bronchitis, breathlessness, and wheezing and associated factors in a sample of
      adults 20 to 59 years of age (n = 2,051). The study employed a cluster sample
      design and Poisson regression analyses. Prevalence rates for chronic bronchitis,
      breathlessness, and wheezing were 5%, 35.7%, and 20.2%, respectively. The
      adjusted analysis showed chronic bronchitis associated with low schooling,
      smoking, and hospital admissions due to respiratory illness during childhood.
      Breathlessness was associated with female gender, low schooling and family
      income, non-white race, hospital admissions due to respiratory illness during
      childhood, smoking, and occupational exposure to dust. Wheezing was associated
      with female gender, low schooling and family income, non-white race, hospital
      admissions due to respiratory illness during childhood, smoking, and occupational
      exposure to dust. Public health planners should consider climatic factors and
      work activities when developing activities to prevent respiratory diseases.

PMID- 19750379
TI  - [Physical activity among health professionals from south and northeast Brazil].
AB  - This cross-sectional study analyzed 240 primary healthcare units, linked either
      to the traditional primary care model or the Family Health Program (FHP),
      involving a total of 3,347 health professionals who answered the International
      Physical Activity Questionnaire. Prevalence of sedentary lifestyle (< 150 minutes
      of physical activity per week) was 27.5% (95%CI: 25.9-29.0). Sedentary lifestyle
      was more frequent among health professionals in the traditional model, with the
      difference explained by the presence of community health agents, whose work only
      involves extensive physical activity in the FHP model. Sedentary health
      professionals were proportionally more common in large cities with better
      socioeconomic conditions. The study highlights the importance of education for
      health professionals aimed at orientation and practice in physical activities and
      collaboration between primary healthcare workers and physical education teachers.

PMID- 19750380
TI  - [Stroke prevalence among the elderly in Vassouras, Rio de Janeiro State, Brazil,
      according to data from the Family Health Program].
AB  - This study estimated the prevalence of stroke among the elderly in Vassouras, Rio
      de Janeiro State, Brazil, based on data from the Family Health Program (FHP). The
      elderly population was chosen since it is growing as a proportion of the general
      population, and since stroke risk increases with age. Data were screened for all
      the elderly registered in the FHP in Vassouras, identifying those with a history
      of stroke and analyzing their socio-demographic profile. The study used data from
      the Information System on Primary Care, the population census conducted by the
      Brazilian Institute of Geography and Statistics (IBGE), and the Ministry of
      Health's standardized FHP patient form. Quality of stroke diagnoses in the FHP
      was analyzed. Data screening detected 122 elderly with a history of stroke
      diagnosis (prevalence = 2.9%; 3.2% in men, 2.7% in women) and a progressive
      increase with age. The prevalence rate was the same in the rural and urban area
      of the municipality (2.9%). Knowledge of stroke prevalence in the elderly
      population is essential to improve health planning.

PMID- 19750381
TI  - [Specific dengue transmission conditions at the local level: a study in Itaipu,
      Niteroi, Rio de Janeiro State, Brazil].
AB  - This study analyzes the specific conditions involved in dengue transmission in
      various areas in Itaipu, a coastal neighborhood in the city of Niteroi, Rio de
      Janeiro State, Brazil, with a focus on socio-environmental determinants and
      conditioning factors. Four areas were selected with similar dengue incidence
      rates but different urban planning and socioeconomic patterns. The socio-spatial
      characteristics of each area were obtained through interviews with key informants
      and systematic observation. Two distinct factors were identified that may
      potentially condition the risk of dengue transmission. The first related to the
      limited water supply and scarce financial resources in a lower-income population.
      The second was associated with a group having better socioeconomic status, which
      allowed them to store water in larger tanks. The implementation of a housing
      infrastructure generated by real estate speculation was a determining factor for
      the creation of socio-spatial segregation, resulting in different forms of
      receptiveness and vulnerability to dengue. In this sense, the incomplete and
      unequal installation of housing infrastructure is a determining factor for the
      differentiated generation of vector breeding sites and thus for dengue
      transmission.

PMID- 19750382
TI  - [How health activities view man and how man rethinks them: an anthropological
      analysis of Chagas disease control].
AB  - This anthropological study addresses the cultural perceptions of a group of
      residents in the city of Bambui, Minas Gerais State, Brazil, in relation to
      experience with Chagas disease and the impact of health measures on social life.
      The ethnographic study was based on open interviews, seeking to identify
      individual perceptions among 35 inhabitants of Bambui (with and without Chagas
      disease) living in the region since the 1940s, when Chagas disease control
      activities were launched. Within a broad analysis of social perceptions
      concerning the effect of these health measures, the study sought to observe the
      cultural representations of the illness process. The study is intended to
      contribute to comprehensive work in health interventions, including the target
      population's socio-cultural characteristics. The cultural perspective plays an
      important role in preventing social distress.

PMID- 19750383
TI  - [Predictors of subjective burden for families of psychiatric patients treated in
      the public health care system in Belo Horizonte, Minas Gerais State, Brazil].
AB  - This study investigated the predictors of subjective burden for families of
      psychiatric patients. We interviewed 150 relatives of patients randomly selected
      in four mental health care services in Belo Horizonte, Minas Gerais State,
      Brazil. Subjects were interviewed with the Family Burden Interview Schedule (FBIS
      BR) and a standardized socio-demographic questionnaire. Variables were grouped
      into thematic categories and separately analyzed to determine the relative
      importance of predictive factors. The results showed that subjective burden is
      influenced by objective burden and by factors related to the patient's clinical
      condition, the caregiver's and patient's living and health conditions and
      financial status, and increased demand for information on mental illness.
      Subjective burden was less when the caregiver practiced leisure and religious
      activities, publicly admitted to being the caregiver of a psychiatric patient,
      and had positive feelings toward the patient. The findings highlight the need to
      include family follow-up in the community model for psychiatric care.

PMID- 19750384
TI  - Factors associated with sexual initiation and condom use among adolescents on
      Santiago Island, Cape Verde, West Africa.
AB  - The current study focuses on factors associated with sexual initiation and condom
      use among teenagers on Santiago Island, Cape Verde, according to gender. This was
      a representative, probabilistic sample of 13-to-17-year-olds (n = 768) attending
      public secondary schools on Santiago Island in 2007. Associations were tested by
      test of proportion, Pearson's chi-square, or Fisher's exact test and logistic
      regression. Factors related to sexual initiation among boys were: age over 14
      years, Catholic religion, and alcohol consumption. For girls, the factors
      included: > 9 years of schooling and involvement in an affective-sexual
      relationship. Unlike other Sub-Saharan countries, this study showed a high
      prevalence of condom use during initial sexual activity. Adolescents are able to
      safely begin sexually active life if they have access to information, sex
      education, and other STD prevention and contraceptive methods. This study
      provides insights on the development of policies to reduce the vulnerability of
      the young population to STD/AIDS and the limits and challenges related to the
      promotion of condom use and sex education, focusing on unequal gender relations.

PMID- 19750385
TI  - [Maternal and neonatal characteristics and early neonatal mortality in greater
      metropolitan Sao Paulo, Brazil].
AB  - The objective was to describe maternal and neonatal characteristics and early
      neonatal mortality rate according to place of delivery in Greater Metropolitan
      Sao Paulo, Brazil. The study linked the databases on live births and early
      neonatal deaths with the national hospital registry. Place of delivery was
      identified through certificates of live birth. There were a total of 154,676 live
      births: 98.7% in-hospital; 0.3% home deliveries, and 1% in other health services.
      Deliveries in birthing centers and small hospital units were associated with low
      obstetric risk and a low proportion of preterm and low birth weight infants, and
      as a result these services showed the lowest early neonatal mortality rate.
      Compared to hospital maternity ward deliveries, the early neonatal mortality rate
      was 4.7 times higher for home deliveries and 9.6 higher for emergency room
      deliveries. There is a high rate of hospital delivery care in Sao Paulo, but
      there is still a small portion of accidental home births and deliveries occurring
      in inappropriate health services, probably as a result of obstetric emergencies
      and difficulties in accessing hospital services.

PMID- 19750386
TI  - [Self-rated health and social inequalities, Buenos Aires, Argentina, 2005].
AB  - Self-rated health is a quality-of-life indicator. This study investigates the
      impact of individual-level and neighborhood-level socioeconomic characteristics,
      considered simultaneously, on the state of self-rated health at the individual
      level in Buenos Aires, Argentina. The study employs a two-level (individual and
      neighborhood) multilevel analysis, and the data sources were the 2005 Argentina
      National Risk Factor Survey (multistage probabilistic sample) and the 2001
      Population Census. Linear regression shows that higher schooling and income, as
      well as occupational category, are related to better self-rated health, and
      increasing age with worse health. In the multilevel analysis, an increase in the
      proportion (per census tract) of individuals with less schooling was associated
      with an increase in the proportion of individuals with worse self-rated health.
      Improving the general health of the population requires strategies and action
      that reduce the levels of social inequalities in their multiple dimensions,
      including the individual and neighborhood levels.

PMID- 19750387
TI  - [Use of clinical guidelines and the results in primary healthcare for
      hypertension].
AB  - This study aimed to identify strategies to implement clinical guidelines for
      hypertension in a primary healthcare unit, focusing on the effects of the Family
      Health Program (FHP) and government Pharmaceutical Home Delivery Program (PHDP)
      on adherence to guidelines by health professionals and the results of care. The
      data were obtained from a registry of 5,499 hypertensive patients, stratified
      according to registration in the FHP and PHDP. The random selection procedure
      resulted in samples of 150 patient charts in three strata and one stratum
      (without the FHP or PHDP) with only 22 patient charts. Descriptive statistics and
      linear regression models were obtained, incorporating the structural information
      from the sample design (sample strata and weight). Based on information recorded
      on the patient charts, adherence to clinical guidelines was extremely low. A
      positive effect had been expected from the FHP and PHDP in terms of adherence to
      clinical guidelines and results of care. A trend towards a positive effect was
      observed for the PHDP and a slightly favorable performance for the FHP for
      adherence to clinical guidelines.

PMID- 19750388
TI  - [Quaternary prevention in primary care: a necessity for the Brazilian Unified
      National Health System].
AB  - In 2003, the World Organization of National Colleges, Academies, and Academic
      Associations of General Practitioners/Family Physicians (WONCA) proposed a
      concept (that had previously received relatively little discussion) aiming to
      protect patients from unnecessary medical interventions and to prevent
      iatrogenicity: quaternary prevention. In times of intense social medicalization,
      particularly in Brazil due to the expansion of health care through the Family
      Health Strategy, iatrogenicity has become a highly relevant issue for both public
      health and the Unified National Health System (SUS). This article presents the
      concept of quaternary prevention and discusses and frames its relevance in light
      of three common situations in medical care with potentially iatrogenic results:
      excessive screening, complementary tests, and medicalization of risk factors. We
      propose the inclusion and discussion of this concept in the SUS, especially in
      primary care.

PMID- 19750389
TI  - Contraceptive discontinuation and non-use in Santarem, Brazilian Amazon.
AB  - In this paper we discuss the causes of non-adherence to reversible
      contraceptives, especially hormonal methods, among women in rural Santarem in the
      Brazilian Amazon. The analysis is based on questionnaires with 398 women and
      visits to health centers. We consider the motives reported by women who: never
      used contraception; used some method in the past; and who at the time of the
      survey were using a different method from the ones they used in the past. The
      results indicate a rejection of hormonal contraception and a preference for
      female sterilization, an option possibly influenced by the characteristics of
      health services in the region. The side effects of hormonal contraceptive use
      reported by part of the interviewees contribute to a generalized fear of the side
      effects even among women who have never used such methods. To improve women's
      health services in the Amazon, we recommend further studies of the relationship
      between reported side effects and available services and prescriptions, as well
      as an analysis of women's discourse and perceptions.

PMID- 19750390
TI  - [Mental health and the Family Health Program: pathways and obstacles in a
      necessary approach].
AB  - The focus of this study is mental health care in the Brazilian Family Health
      Program (FHP), with the complexity of such care as the main premise. The
      objectives were to analyze the actual conditions of mental health care in FHP
      services in Cuiaba, Mato Grosso State, describing the dynamics of such care and
      identifying situations and instruments used by different health professionals in
      dealing with problems of mental distress in the community. By means of a
      descriptive exploratory methodology, the discourses of eight health teams were
      studied, using content analysis. The study concluded that the demand for care for
      individuals with mental distress was not recorded on the patient charts, nor was
      it part of a proposal for individual or family interventions; some measures were
      taken according to a lay concept of 'mental illness' and treatment, while
      referral to the specialized mental health care network was frequently used,
      despite its precariousness, thus reflecting the need for continuing training in
      mental health.

PMID- 19750391
TI  - Establishing the risk of neonatal mortality using a fuzzy predictive model.
AB  - The objective of this study was to develop a fuzzy model to estimate the
      possibility of neonatal mortality. A computing model was built, based on the
      fuzziness of the following variables: newborn birth weight, gestational age at
      delivery, Apgar score, and previous report of stillbirth. The inference used was
      Mamdani's method and the output was the risk of neonatal death given as a
      percentage. 24 rules were created according to the inputs. The validation model
      used a real data file with records from a Brazilian city. The receiver operating
      characteristic (ROC) curve was used to estimate the accuracy of the model, while
      average risks were compared using the Student t test. MATLAB 6.5 software was
      used to build the model. The average risks were smaller in survivor newborn (p <
      0.001). The accuracy of the model was 0.90. The higher accuracy occurred with
      risk below 25%, corresponding to 0.70 in respect to sensitivity, 0.98
      specificity, 0.99 negative predictive value and 0.22 positive predictive value.
      The model showed a good accuracy, as well as a good negative predictive value and
      could be used in general hospitals.

PMID- 19750392
TI  - Voluntary counseling and testing (VCT) services and their contribution to access
      to HIV diagnosis in Brazil.
AB  - The Voluntary Counseling and Testing (VCT) Network was implemented in Brazil in
      the 1980s to promote anonymous and confidential access to HIV diagnosis. As a
      function of the population and dimensions of the local epidemic, the study
      assessed the network's coverage, using data from a self-applied questionnaire and
      data from the Information Technology Department of the Unified National Health
      System (SUS), UNDP, and National STD/AIDS Program. The Student t test was used
      for comparison of means and the chi-square test for proportions. Brazil has 383
      VCT centers, covering 48.9% of the population and 69.2% of the AIDS cases. The
      network has been implemented predominantly in regions where the epidemic shows a
      relevant presence, but 85.3% of the cities with high HIV incidence lack VCT
      centers; absence of VCT was associated with more limited health infrastructure
      and worse social indicators. A slowdown in expansion of the network was observed,
      with VCT Centers implemented on average 16 years after the first AIDS case in the
      given municipality. The number of HIV tests performed under the SUS is 2.3 times
      higher in cities with VCT centers. The network's scope is limited, thus
      minimizing the contribution by these services to the supply of HIV diagnosis in
      Brazil.

PMID- 19750393
TI  - [Prevalence of mental disorders associated with suicide attempts treated at an
      emergency hospital in Rio de Janeiro, Brazil].
AB  - There are few Brazilian studies on prevalence of mental disorders in suicide
      attempters. The available studies have mainly used secondary data and screening
      instruments. The principal objective of this study was to estimate the prevalence
      of mental disorders in 96 suicide attempters seen in an emergency ward in Rio de
      Janeiro, Brasil (2006-2007) using the Composite International Development
      Interview. Most were female, young, and illiterate, and the main method was
      ingestion of psychoactive drugs. Other factors included history of prior attempts
      and use of alcohol at the time of attempt. The most frequent mental disorders
      were: depression (38.9%), use of psychoactive substances (21.9%), posttraumatic
      stress disorder (20.8%), alcohol abuse (17.7%), and schizophrenia (15.6%). Total
      prevalence of mental disorders was 71.9%. These findings are largely consistent
      with studies conducted in other developing countries. Besides access to treatment
      for mental disorders, public policies with an emphasis on the control of suicide
      methods and social responses for the reduction of suicidal behavior are needed.

PMID- 19750394
TI  - A proposal for an evaluation model of pharmaceutical services for malaria.
AB  - Malaria is a serious public health problem in over 90 countries worldwide. In
      Brazil the disease is prevalent in the Amazon and the control rationale is based
      on early diagnosis and treatment. Quality pharmaceutical services are considered
      a key element for control. A proposal for evaluating pharmaceutical services for
      malaria is presented here. A theoretical outline composed of a logical model and
      an indicator framework is discussed and strives to establish a basis for
      assessment and judgment of the way in which these services are actually
      delivered. The aim is to contribute to the understanding of pharmaceutical
      services for malaria and other endemic diseases, complying with the directives of
      the Brazilian National Medicines Policy.

PMID- 19750395
TI  - [Declaration of Istanbul on Global Health].

PMID- 19750398
TI  - Beauty and belief: William James and the aesthetics of delusions in
      schizophrenia.
AB  - INTRODUCTION: This paper proposes the hypothesis that aesthetics plays an
      important role in the construction and maintenance of delusional ideas in
      schizophrenia. METHOD: A selective review of the literature on the cognitive
      science of aesthetics, beginning with the work of William James on the stream of
      thought, was undertaken together with a review of some of the cognitive
      neuroscience literature on delusion formation in schizophrenia. RESULTS: It is
      suggested that delusion formation has some similarities to to the creative
      process, but commences with a proto-psychotic anomalous experience in which an
      aberrant Jamesian fringe experience is generated. The consequence of such
      deviation from standard or expected conscious experience is to direct processing
      resources in a search for meaning, but under conditions of reduced prefrontal
      cortex monitoring and control mechanisms. Lowering of the usual constraints
      exercised by prefrontal cortex regulatory mechanisms causes the search for
      explanation or interpretation to be characterised by low self-reflection,
      temporal distortion and low volitional control, permitting relatively unfiltered
      ideas that do not conform to convention to emerge in consciousness. The
      combination of aberrant Jamesian fringe experience and reduced prefrontal
      regulatory mechanisms evoke idiosyncratic contextual associations and drive a
      hypersensitive salience assignment system in the search for meaning, out of which
      process nascent delusional beliefs emerge. These are accompanied by a 'sense of
      rightness' in the Jamesian fringe which signals the presence of a 'good fit'
      between the proto-psychotic anomalous experience in the centre of consciousness
      and the contextual associations evoked. CONCLUSION: The 'sense of rightness' or
      'good fit' is responsible for the aesthetic qualities of the delusion and, it is
      proposed, accounts for the incorrigibility of the delusions.

PMID- 19750399
TI  - Temporal consciousness and confabulation: is the medial temporal lobe "temporal"?
AB  - Since the early descriptions of this phenomenon, there is a large consensus on
      the distinction between two forms of confabulation. Provoked confabulations are
      plausible minor memory distortions in response to direct questioning, whereas
      spontaneous confabulations are unprovoked, often implausible, memories. However,
      as we show with the analysis of 284 provoked and 52 spontaneous confabulations
      produced by eight patients with confabulatory syndromes of different aetiologies,
      the provoked/spontaneous distinction fails to capture the quality of the great
      majority of confabulations that clearly do not fall in either of the two poles of
      the distinction. In this study, the majority of provoked (52%) and spontaneous
      (73%) confabulations consisted of what we refer to as "general memories, habits,
      and misplacements", i.e., either true episodes misplaced in time and place, or
      personal habits and routines which are considered by the patient as specific
      personal episodes. These observations are discussed within the framework of the
      Memory, Consciousness, and Temporality Theory. According to this theory,
      confabulation reflects an abnormal functioning of temporal consciousness (TC).
      The integrity of the medial temporal lobe (MTL) and related structures is crucial
      for the normal functioning of TC. Data from the literature show that what
      confabulators have in common is not a specific lesion site but rather the
      integrity of the MTL, which is consistent with the idea that the MTL is essential
      for the function of normal and confabulatory TC. In this sense the MTL is
      "temporal", because its integrity allows individuals to be consciously aware of a
      personal past, present and future. A better understanding of TC, including its
      neurobiological correlates, will help to better understand confabulation avoiding
      theoretically untenable and experimentally undemonstrated explanatory idols like
      memory traces and unconscious monitoring.

PMID- 19750400
TI  - Effect of the inclusion of adsorbents on aflatoxin B1 quantification in animal
      feedstuffs.
AB  - The extraction efficiency of aflatoxin B1 (AFB1) in cattle feed containing nine
      adsorbents (ADSs) was investigated using two organic/aqueous solvents composed of
      methanol/water (80/20 v/v; MeOH) and acetone/water (85/15 v/v; AC). Samples were
      obtained including a highly AFB1-contaminated (HC) and a low-level AFB(1)
      contaminated (LC) feedstuff (15.33 and 7.57 microg kg(-1), respectively), nine
      ADSs (four clay minerals; one yeast cell wall-based product; one activated carbon
      and three commercial ADS products) at two different levels of inclusion (10 and
      20 g kg(-1)). After solvent extraction and immunoaffinity column clean-up, all
      samples were analysed for AFB1 by high-performance liquid chromatography (HPLC)
      with fluorescence detection. For each contamination level (HC and LC), the data
      obtained were analysed using a factorial arrangement in a completely randomized
      design. Means were compared with the correspondent controls using the Dunnett's
      test. No statistical difference was found in AFB1 levels of feedstuffs not
      containing ADSs when extracted with AC or MeOH, even if numerically higher values
      were obtained with AC. A dose-dependent effect (p < 0.01) of ADSs inclusion was
      observed on AFB1 recoveries that were lower when the higher ADS level (20 g kg(
      1)) was included in the HC and LC feedstuffs. Higher AFB(1) recoveries were
      obtained using AC compared with MeOH, both in HC (75.0% versus 12.0%,
      respectively) and in LC (84.0% versus 22.8%, respectively) ADSs containing
      feedstuffs. However, when the activated carbon and the sodium bentonite were
      included in feeds, lower AFB1 concentrations with respect to control values (p <
      0.001 and <0.05, respectively) were obtained also using AC. The data obtained in
      this study indicate that routine use of the MeOH solvent for AFB1 analysis of
      unknown feedstuffs, can produce misleading results if they contain an ADS.

PMID- 19750401
TI  - Non-essential and essential trace element concentrations in meat from cattle
      reared under organic, intensive or conventional production systems.
AB  - We evaluated if differences in non-essential and essential trace element
      accumulation in beef-cattle reared under different systems (including organic,
      conventional and intensive management) were reflected in the meat derived from
      these animals. Diaphragm muscle from 166 calves from nine farms were analysed.
      Muscle cadmium concentrations were low (<10 microg/kg wet weight) and muscle
      arsenic, mercury and lead levels were below the limits of detection (<12, 2 and 3
      microg/kg, respectively) in most (77-97%) samples; there were no significant
      differences between farms. Essential trace element concentrations in muscle were
      generally within adequate physiological ranges and, although they varied
      significantly between farms, this was not apparently related to management
      practices. There were no significant correlations in element concentrations
      between muscle and liver or kidney (organ concentrations that better reflect
      exposure), except for cobalt (positive association) and zinc (negative
      association). Non-essential and essential trace element concentrations in muscle
      in the studied animals did not generally reflect differences in exposure. This is
      particularly relevant for animals reared in systems (such as organic farms) where
      cattle are exposed to higher levels of non-essential elements (probably due to
      soil ingestion when grazing) but also can suffer from mineral deficiencies.

PMID- 19750403
TI  - Meeting Report: 4(th) Biennial meeting of the Society for Free Radical Research -
      Asia, held during July 9-12, 2009 at Langkawi, Malaysia.

PMID- 19750402
TI  - Validation of a liquid chromatography-mass spectrometry method for determining
      the migration of primary aromatic amines from cooking utensils and its
      application to actual samples.
AB  - Many cooking utensils are made of nylon, a material that may incorporate azodyes
      and where primary aromatic amines (PAAs) are the starting substances. Moreover,
      aromatic amines may also be present as technical impurities. Another source of
      PAAs could be aromatic isocyanates used as monomers in the production of
      polyurethanes. The aim of this work was to validate a simple LC-MS/MS method for
      the determination of eight primary aromatic amines (m-phenylenediamine, 2,6- and
      2,4-toluenediamine, 1,5-diaminonaphthalene, aniline, 4,4'-diaminonaphenylether,
      4,4'-methylenedianiline and 3,3'-dimethylbenzidine) in the aqueous food simulant
      3% acetic acid (w/v). The detection limits calculated were adequate with respect
      to present legislation. The method was validated at four concentration levels (2,
      5 10 and 20 microg kg(-1)). Global internal reproducibility was in the range 5.6
      21.4% (RSD(R)) depending on the compound and concentration. Mean recoveries for
      all levels varied between 89 and 100%, depending on the amine. A total of 39
      samples of cooking utensils were analyzed using the described method and the
      results obtained after the third migration test were not compliant in
      approximately half of the samples.

PMID- 19750404
TI  - The increase in human plasma antioxidant capacity after acute coffee intake is
      not associated with endogenous non-enzymatic antioxidant components.
AB  - This study evaluated the association between the main plasma endogenous non
      enzymatic antioxidant components and the increase in human antioxidant capacity
      (AC) after acute coffee intake. Ten adults were tested before and 90 min after
      consumption of coffee or water, in a crossover design, with a 7-day interval
      between tests. AC (FRAP and TRAP), ascorbic acid, alpha-tocopherol and gamma
      tocopherol, albumin, bilirubin and uric acid were analyzed in plasma/serum. After
      coffee consumption FRAP and TRAP increased 2.6% and 7.6% (P<0.05), whereas after
      water consumption FRAP and TRAP decreased 2.5% and 1.0% (P <0.05), respectively.
      In general, AC assays correlated with uric acid and alpha-tocopherol (r >0.75; P
      <0.04), independently of treatment and time point. Changes in AC assays after
      coffee intake did not correlate with endogenous components, which remained
      unchanged. These results suggest that coffee components spare endogenous
      antioxidants or are themselves the main contributors to plasma AC increase after
      coffee intake.

PMID- 19750405
TI  - Ergonomics case study: revised NIOSH lifting equation instruction issues for
      students.
AB  - This case study investigated the effectiveness of formal instruction of the
      Revised NIOSH Lifting Equation for university students who may use the equation
      in their future work. Their successes and challenges were examined through a
      class exercise and two exams, all of which followed the classroom instruction in
      applying the Lifting Equation. Results showed students (1) had difficulty
      determining relevant values for task variables from reading a job description,
      and (2) generally were able to calculate the Recommended Weight Limit (RWL) and
      Lifting Index (LI) when task variables were such that the associated multipliers
      were less than or equal to 1. However, when the multiplier was calculated to be
      greater than 1, students had difficulty interpreting the result. The task
      variable and multiplier (consistently the greatest challenge) were the asymmetry
      task variable, A, and the asymmetric multiplier, AM. Results indicate that the
      layout of the Job Analysis Worksheet for Step 1 may make it easy to make
      arithmetic errors when calculating multipliers. It is recommended that the
      worksheet be redesigned to help individuals decrease the probability of making an
      arithmetic error when calculating the task variables, multipliers, RWL, and LI.
      It is also recommended that the redesigned worksheet be tested to determine
      whether fewer arithmetic errors are made and if the worksheet is less confusing
      for an inexperienced user to use.

PMID- 19750406
TI  - Modeling of oil mist and oil vapor concentration in the shale shaker area on
      offshore drilling installations.
AB  - The objective of this study was to develop regression models to predict
      concentrations of oil mist and oil vapor in the workplace atmosphere in the shale
      shaker area of offshore drilling installations. Collection of monitoring reports
      of oil mist and oil vapor in the mud handling areas of offshore drilling
      installations was done during visits to eight oil companies and five drilling
      contractors. A questionnaire was sent to the rig owners requesting information
      about technical design of the shaker area. Linear mixed-effects models were
      developed using concentration of oil mist or oil vapor measured by stationary
      sampling as dependent variables, drilling installation as random effect, and
      potential determinants related to process technical parameters and technical
      design of the shale shaker area as fixed effects. The dataset comprised
      stationary measurements of oil mist (n = 464) and oil vapor (n = 462) from the
      period 1998 to 2004. The arithmetic mean concentrations of oil mist and oil vapor
      were 3.89 mg/m(3) and 39.7 mg/m(3), respectively. The air concentration models
      including significant determinants such as viscosity of base oil, mud
      temperature, well section, type of rig, localization of shaker, mechanical air
      supply, air grids in outer wall, air curtain in front of shakers, and season
      explained 35% and 17% of the total variance in oil vapor and oil mist,
      respectively. The developed models could be used to indicate what impact
      differences in technical design and changes in process parameters have on air
      concentrations of oil mist and oil vapor. Thus, the models will be helpful in
      planning control measures to reduce the potential for occupational exposure.

PMID- 19750407
TI  - Evaluation of the WMS-III Rarely Missed Index in a naive clinical sample.
AB  - We examined the WMS-III Rarely Missed Index as a reliable predictor of
      fabrication of memory difficulties. A total of 31 outpatients referred for
      neuropsychological evaluation completed the WMS-III Logical Memory Delayed
      Recognition Test (LMDR) before having heard the stories and again after hearing
      the stories. Of the 30 items from the LMDR completed by participants who had not
      heard the stories, 5 were found to significantly differ from chance; only 1 of
      those items was found to do so in the original RMI studies. Conversely, of the
      six items in the original RMI study, only one was found to differ from chance in
      the present study. A Monte Carlo randomization of the original six RMI items
      found that 69% of random responders fell below cutoffs for incomplete effort,
      suggesting that those with memory impairment severe enough to result in random
      responding are likely to be classified as demonstrating less than optimal effort.
      An examination of response bias found no differences among negative, positive, or
      no-bias responders in terms of overall memory performance. However, RMI was
      indicative of incomplete effort more often with individuals presenting with a
      negative response bias. The present study provides evidence of the limitations of
      using the RMI to detect incomplete effort using the LMDR. The relative values of
      specificity versus sensitivity are particularly important in clinical
      evaluations, with the prevention of false accusations of malingering an important
      goal. The use of multiple indicators of effort is reinforced by this study, and
      the conservative interpretation of the RMI in particular is recommended.

PMID- 19750408
TI  - Effort indicators within the California Verbal Learning Test-II (CVLT-II).
AB  - This study determined whether performance patterns on the California Verbal
      Learning Test-II (CVLT-II) could differentiate participants with traumatic brain
      injury (TBI) showing adequate effort from those with mild TBI exhibiting poor
      effort using a case-control design. The TBI group consisted of 124 persons with
      moderate to severe traumatic brain injury (TBI). The poor effort group consisted
      of 77 persons with mild head injury who were involved in litigation (LG) and
      failed at least one stand-alone symptom validity measure (SVT) and also either a
      second SVT or an effort indicator embedded within a standard clinical test. A
      total of 18 CVLT-II variables were investigated using Bayesian model averaging
      (BMA) for logistic regression to determine which variables best differentiated
      the groups. The CVLT-II variables having the most support were Long-Delay Free
      Recall, Total Recognition Discriminability (d'), and Total Recall
      Discriminability.

PMID- 19750410
TI  - [DGP Newsletter September 2009].

PMID- 19750411
TI  - [Prognostic factors for COPD patients with chronic hypercapnic respiratory
      failure and home ventilation].
AB  - The prevalence of patients with severe COPD and chronic hypercapnic respiratory
      failure (CHRF) receiving non-invasive home ventilation has greatly increased.
      With regard to disease severity, a multidimensional assessment seems indicated.
      Base excess (BE), in particular, reflects the long-term metabolic response to
      chronic hypercapnia and thus constitutes a promising, easily accessible,
      integrative marker of CHRF. Infact, BE as well as nutritional status and lung
      hyperinflation have been identified as independent predictors of long-term
      survival. In addition and in a review with the literature, a broad panel of
      indices including frequent comorbidities are helpful for assessment and
      monitoring purposes of patients with CHRF. Accordingly, in view of the patients'
      individual risk profile, the decision about the initiation of NIV should probably
      not rely solely on symptoms and chronic persistent hypercapnia but include a
      spectrum of factors that specifically reflect disease severity. Owing to the
      physiologically positive effects of NIV and according to retrospective data,
      patients with COPD and recurrent hypercapnic respiratory decompensation and
      patients with prolonged mechanical ventilation and/or difficult weaning could
      also be considered for long-term non-invasive ventilation. This, however, has to
      be corroborated in future prospective trials.

PMID- 19750412
TI  - [Tuberculosis and travelling].
AB  - Tuberculosis (TB) in Germany in the year 2007 with 5020 reported cases
      (incidence: 6.1 newly diagnosed cases per 100 000 inhabitants) was continuously
      in decline. 43.1 % of these persons were from countries with a higher TB
      incidence as compared to Germany. However, not only migration but also personal
      journeys from low- to high-incidence countries carries an increased risk of
      infection with M. tuberculosis (MTB). An early active TB follows only rarely,
      more common, however, is a latent TB infection (LTBI). Not only the active form
      of TB but also LTBI, with a potential for reactivation years or decades later,
      can be of enormous relevance for the individual and the social environment. The
      early detection of an MTB infection and its possible sequelae are decisive for a
      continued successful battle against tuberculous diseases, especially in view of
      increasing travel activities.

PMID- 19750413
TI  - [COPD and concomitant diseases].

PMID- 19750414
TI  - [Update: diagnosis and therapy of tropical diseases - part 1].

PMID- 19750415
TI  - [New and well-tried].

PMID- 19750416
TI  - ["Introduction to heavy vitreous tamponades"].

PMID- 19750417
TI  - [Heavy tamponades--background and future perspectives].
AB  - Proliferative vitreoretinopathy in the inferior retina remains clinically
      challenging. Heavier-than-water intraocular tamponades have been developed to
      improve inferior tamponading properties. The parameters of an optimal intraocular
      tamponade are defined and the influences of the specific gravity, buoyancy,
      interfacial tension, and viscosity are discussed. Perfluorocarbon liquids and
      partially fluorinated alkanes were associated with tamponade emulsification,
      intraocular inflammation, and rises in intraocular pressure that were less
      prominent in admixtures of these substances with silicone oil (heavy silicone
      oils). Two recently developed heavy silicone oil tamponades, Oxane HD and
      Densiron 68, are well tolerated and have entered clinical practice. The side
      effects are associated with the chemical properties of the tamponading agent and
      seem comparable to those seen with conventional silicone oil. Heavy silicone oil
      tamponade improves inferior tamponade and may be considered as a new generation
      of intraocular tamponades.

PMID- 19750418
TI  - [Heavy silicone oil endotamponade--a useful alternative to conventional
      endotamponade].
AB  - Retinal surgery of retinal detachment in the inferior part of the eye is often
      complicated by the development of proliferative vitreoretinopathy. Therefore the
      heavier-than-water concept using heavy silicone oils is a logical consequence for
      treatment of otherwise unsuccessful retinal surgery in such cases. While some
      surgeons already use heavy silicone oils in the clinical routine, others are
      carefully following complication rates. Even good anatomical and functional
      results are published as critical case reports. In this report we describe the
      advantages of the heavy silicone oil endotamponade and our own clinical
      experiences with Densiron(R) 68. The use of heavy silicone oils turned out to be
      quite convenient, leading for example to shorter tamponade times, easy handling
      of the oil, no need for uncomfortable prone-position of the patients. On the
      other hand one has to consider that Densiron(R) 68 is a mixture which contains 70
      % PDMS and 30 % F 6 H8, a heavy fluid that was associated with multiple
      complications if used as sole long-term endotamponade. Based on these experiences
      we recommend all users bear in mind possible complications. However, such
      complications can be prevented.

PMID- 19750419
TI  - [Are heavy silicone oils unnecessary in vitreoretinal surgery?].

PMID- 19750420
TI  - Long-term evaluation of anatomic and functional results after complicated retinal
      detachment treated with pars plana vitrectomy and heavy silicone oil tamponade.
AB  - BACKGROUND: Heavier than water tamponades offer the possibility to support the
      inferior part of the fundus after retinal detachment. The aim of this study was
      to evaluate the anatomic and functional outcome of complicated retinal detachment
      treated with vitreous surgery and heavy silicone oil (HSO) tamponade. Surgery was
      performed in eyes with rhegmatogenous retinal detachment (RD) predominantly in
      the lower hemisphere or with penetrating injury (either as primary intervention
      or after development of proliferative vitreoretinopathy [PVR]). MATERIALS AND
      METHODS: Sixty-one eyes of 61 patients with RD - mostly complicated by PVR - and
      a minimum follow-up of 12 months were included in this study. Vitreoretinal
      surgery with HSO (Oxane HD) tamponade was performed in all patients. In 52
      patients, heavy silicone oil was used in the management of complicated RD. 9
      patients had surgery for complicated RD after penetrating eye injury.The mean
      follow-up period was 30.3 +/- 10.2 months. RESULTS: The overall final anatomic
      success rate was 79 %. In 39 % of the cases the retina remained attached during
      the entire follow-up period. CONCLUSIONS: The anatomic success rate after surgery
      with HSO (Oxane HD) was relatively low; however, only complex cases bearing a
      higher risk of retinal re-detachment received HSO in this study. Oxane HD does
      not appear to have major advantages compared to conventional silicone oil or
      other new-generation heavy silicone oils in these cases.

PMID- 19750421
TI  - [Alternative indications for the use of heavy silicone oil tamponades].
AB  - BACKGROUND: The heavy silicone oil tamponades Densiron and Oxane HD are gaining
      in popularity amongst vitreoretinal surgeons over recent years. In addition to
      the classical indications of complicated retinal detachment and PVR, the spectrum
      is continuously expanding and includes diseases that up to now have been treated
      with conventional tamponades. MATERIAL AND METHODS: Review of recent studies on
      vitreoretinal surgery with heavy tamponades outside of surgery for PVR and
      retinal detachment. RESULTS: In macular hole surgery, good to excellent anatomic
      and functional results have been reported using heavy tamponades with primary
      closure rates of up to 100 % of the cases. In reoperations of reopened macular
      holes, the reported success rates were between 60 % and 100 %. In the group of
      patients with foveoschisis or central retinal detachment in high myopia with or
      without macular hole, relatively high reattachment rates of up to 83 % of the
      cases have been reported. Other reported indications for the use of heavy
      tamponades are retinoschisis, retinal necrosis, endophthalmitis, proliferative
      diabetic retinopathy, branch retinal vein occlusion, retinopathy of prematurity,
      hypotony and choroidal detachment. The published complication rates are low and
      do not exceed those of conventional tamponades. CONCLUSION: The spectrum of
      indications for heavy tamponades is constantly expanding. In addition to retinal
      detachment and PVR surgery, macular holes, reopened macular holes and central
      retinal detachments or foveoschisis associated with high myopia seem to be the
      most important diseases that are currently treated with heavy tamponades with
      good to excellent results published so far. However, a comprehensive comparison
      with conventional tamponades cannot be made at present because of the limited
      number of patients and studies published on this subject.

PMID- 19750422
TI  - [Vitreous substitutes as drug release systems].
AB  - Despite major improvements of vitreo-retinal surgical techniques proliferative
      vitreoretinopathy (PVR) remains a major challenge. Surgical therapy alone may not
      be sufficient in complicated cases of PVR. A combination of standard techniques
      such as pars plana vitrectomy with a vitreous substitute and a simultaneous
      adjuvant pharmacological treatment for the suppression of undesired proliferation
      of retinal cells and retinal scarring may be a promising therapeutic approach.
      However, due to the narrow therapeutic range and the short biological half-life
      of most anti-proliferative or anti-inflammatory drugs in the vitreous cavity,
      intravitreal slow-release systems for extended drug delivery are desirable.
      Vitrectomy for PVR normally requires a vitreous substitute. Consequently, a
      vitreous substitute that could also serve as a slow-release system for anti
      proliferative or anti-inflammatory drugs would provide several advantages. This
      review gives an overview of recent developments of slow-release systems that may
      also be suitable as vitreous substitutes. Even standard internal tamponades such
      as silicone oils or gases may serve as extended drug-release systems under
      certain conditions. In the mean time polymerised hydrogels have been developed,
      which apart from providing an adequate tamponade effect, may facilitate an
      extended intravitreal release of various anti-proliferative and anti-inflammatory
      drugs for several weeks.

PMID- 19750423
TI  - [The situation of ophthalmic pathology in Germany: the current status].
AB  - BACKGROUND: Ophthalmic pathology with its 150 year-old tradition is a
      subspecialty which since its beginning has contributed substantially to progress
      in ophthalmology. Nevertheless, deactivation or even termination of
      ophthalmopathological laboratories has occurred in the past years mainly due to
      economic pressure. In order to evaluate the situation and future perspectives of
      the existing, active laboratories in Germany and to ask for the kind of support
      desired from the Section for Ophthalmic Pathology of the German Ophthalmological
      Society (DOG) a survey was carried out using a questionnaire. RESULTS: The main
      results were as follows. 1. Specialised ophthalmic pathology is performed in
      Germany almost exclusively in laboratories integrated in university eye clinics.
      2. There is close cooperation with institutes for pathology and dermatopathology.
      3. The main focus is placed on the cornea, tumours of the eye and its adnexae,
      and the conjunctiva. 4. The number of ophthalmopathological specimens
      investigated per year is generally below 1000 and often below 500. 5. The
      diagnostic spectrum and equipment of the laboratories is generally good. 6. There
      are some deficits concerning ophthalmopathological education and the status of
      ophthalmic pathology within the clinics. 7. A considerable number of scientific
      publications is generated by the members of the laboratories. 8. At present there
      is only minimal fear that the own laboratory will be eliminated in the near
      future. 9. Ophthalmic pathology is established as an integral component of
      ophthalmology in patient care and, even more, in ophthalmic research. 10. The DOG
      Section "Ophthalmic pathology" is requested to initiate stays in foreign
      laboratories, to initiate scientific multicentre studies, and to support
      activities dedicated to preserve the ophthalmopathological laboratories.
      DISCUSSION: For the first time valid data concerning the situation of
      ophthalmopathological laboratories in Germany have been collected. The
      information gathered can and should be used as an argument for the preservation
      and, if possible, even expansion of the occupation with normal and pathologic eye
      morphology at eye hospitals in and beyond Germany.

PMID- 19750424
TI  - [Changes in corneal first-surface wavefront aberration after corneal collagen
      cross-linking in keratoconus].
AB  - BACKGROUND: Collagen cross-linking with administration of riboflavin and UV
      radiation may delay or halt the progression of keratoconus. This study examines
      the effects of the treatment on the corneal wavefront error. MATERIALS AND
      METHODS: Twenty eyes of 20 patients with keratoconus received collagen cross
      linking with riboflavin administration and 30 min of UV radiation at a wavelength
      of 365 nm. Preoperatively as well as 1 and 6 months postoperatively, the corneal
      wavefront error was computed from axial keratometric topography data by Zernike
      decomposition over a pupil diameter of 6 mm. RESULTS: Preoperative mean
      keratometric astigmatism was 5.37 +/- 2.36 D. Six months postoperatively it was
      5.29 +/- 2.73 D (p = 0.35). Total higher order aberrations were preoperatively
      3.35 +/- 1.65 microm and after 6 months 3.31 +/- 1.79 microm (p = 0.116). Coma's
      root mean square was 2.94 +/- 1.47 microm preoperatively and 2.75 +/- 1.38 microm
      after 6 months (p = 0.047). CONCLUSION: Within the first 6 postoperative months,
      collagen cross-linking with riboflavin administration and UVA irradiation does
      not significantly increase or decrease corneal wavefront aberrations.

PMID- 19750425
TI  - [DSAEK for the treatment of endothelial disease: results in the initial 100
      cases].
AB  - PURPOSE: To evaluate the learning curve and the outcome of Descemet Automated
      Endothelial Keratoplasty (DSAEK) in patients with primary or secondary
      endothelial decompensation. METHODS: DSAEK was performed in 100 eyes with
      endothelial decompensation (Fuchs' Dystrophy n = 59; pseudophakic bullous
      keratopathy n = 33; failed corneal graft n = 8). All patients underwent a
      standard procedure including the following steps: Descemet membrane and
      endothelium removal from the recipient cornea under air; inferior peripheral
      iridectomy; microkeratome-assisted preparation of a donor lamella consisting of
      deep stroma and endothelium (between 100 and 200 micron in thickness), which is
      punched to desired size (8.5 to 9 mm) from the endothelial side; graft delivery
      with a specially designed glide; complete anterior chamber air fill to obtain
      firm attachment of the donor lamella and air-tight closure of all surgical
      wounds. In 46 cases phacoemulsification with implantation of an intraocular lens
      into the capsular bag was combined with DSAEK surgery. Visual acuity, refraction
      and endothelial cell count were evaluated prospectively at 1, 3, 6, and 12 months
      after DSAEK. RESULTS: As early as 1 month after surgery 76 of 100 patients had a
      best spectacle-corrected visual acuity (BSCVA) better than or equal to 0.5, with
      a refractive astigmatism within 1.5 Diopters (D). One year after surgery, 79 of
      100 patients had a BSCVA better than or equal to 0.5, with a refractive
      astigmatism within 1.5 D. At this examination time 11 of 100 patients could see
      1.0 or better and the average endothelial cell loss amounted to 22.5 +/- 4.2 %.
      CONCLUSIONS: DSAEK surgery allows fast visual rehabilitation of patients with
      decompensated endothelium. Visual outcome is superior to that of conventional
      penetrating keratoplasty (PK) in terms of BSCVA and early stabilization.
      Endothelial cell loss also compares favourably to that recorded after PK.

PMID- 19750426
TI  - [Re-enclavation of an iris-fixated phakic intraocular lens (artisan) with
      concomitant iritis].

PMID- 19750427
TI  - Acute liver failure in a metropolitan area in Germany: a retrospective study
      (2002 - 2008).
AB  - OBJECTIVES: To determine current etiologies of acute liver failure (ALF) and
      clinical and laboratory parameters associated with the outcome upon ALF, so as to
      identify the frequency of present causes of ALF in Germany as well as potential
      new prognostic parameters. PATIENTS: 134 adult patients (63 % females / 37 %
      males) aged 41 +/- 16 years (median: 38 years) with established ALF criteria.
      DESIGN AND SETTING: A retrospective study (1 / 2002 - 4 / 2008) on ALF patients
      from the Ruhr Area, the largest urban region located in northwestern Germany.
      Clinical and laboratory data were collected for a period of four weeks after
      study admission. RESULTS: Etiologies of ALF were identified as drug toxicity
      (39.6 % of the cases); combined viral hepatitides (23.1 %); or miscellaneous
      (16.4 %). In 20.9 % of the cases, the etiology remained indeterminate. Overall
      patient survival at four weeks was 81.3 %. While 89 patients (66.4 %) recovered
      under best supportive therapy, 26 patients (19.4 %) had to undergo liver
      transplantation. Increased body mass indices were significantly (p < 0.003)
      associated with a poor outcome. Intriguingly, high levels of cholestatic enzymes
      significantly (p < 0.01) correlated with a positive outcome. CONCLUSIONS: In
      providing first data on current ALF etiologies Germany, this study reveals that
      drug toxicity - in particular due to acetaminophen - has replaced viral hepatitis
      as the most single frequent cause of ALF in a densely populated urban area; this
      correlates with similar findings in the USA, the UK and Scandinavia. Lower body
      mass indices and elevated cholestatic enzyme levels had statistically significant
      prognostic power.

PMID- 19750428
TI  - An observational real-time study to analyze junior physicians' working hours in
      the field of gastroenterology.
AB  - BACKGROUND: In recent years, data from questionnaires have demonstrated
      increasing criticism from junior physicians regarding their work conditions.
      Ideally, such subjective statements should be compared to accurate objective data
      regarding workload. However, such data is not available in the research
      literature. Therefore the aim of the current study is to deliver exact data about
      physicians' work in different gastroenterology departments to analyze and to
      optimize work routines. METHOD: An observational real-time study was conducted by
      shadowing 21 gastroenterologists individually during weekday shifts at three
      hospitals in urban German settings. A total of 585 hours of observations were
      recorded by using an ultra mobile computer. RESULTS: The observation results have
      shown that a gastroenterologist's working day lasted on an average 9 hours 16 min
      (SD = 1:11:18 h). The following amount of time was given to varying tasks within
      this time period: 30.21 % for meetings (SD = 8.54 %), 13.42 % for documentation
      duties (SD = 7.74 %), 15.53 % for indirect patient care (SD = 6.32 %), 7.98 % for
      hospital admissions and ward rounds (SD = 5.49 %). Doctor patient communication
      was restricted to 4.05 % of the working day (SD = 2.71 %). CONCLUSION: This is
      the first real time analysis on how hospital gastroenterologists spend their
      working hours. Some of the problems with work routine reported by the doctors
      themselves were partly confirmed. With regard to the study results a
      rearrangement of job tasks coupled with technological solutions may prove helpful
      in reducing the burden on gastroenterologists and thereby improving the quality
      of medical care.

PMID- 19750429
TI  - Unusual right upper quadrant Stump Appendicitis.
AB  - Stump appendicitis is often not considered in patients with a surgical history of
      appendectomy. We report an unusual case of right upper quadrant stump
      appendicitis after previous operation for intussusception with incidental
      appendectomy. Abdominal computed tomographic scan is more efficient to make an
      early diagnosis of stump appendicitis to prevent further complications and
      prolonged hospitalization.

PMID- 19750430
TI  - Penile and scrotal swelling in Crohn's disease: a case report.
AB  - Penile and scrotal swelling considered as metastatic Crohn's disease is described
      in a 23 years-old-man. Clinical features and therapeutic options of this rare
      manifeatation are reviewed.

PMID- 19750431
TI  - [Palliative care in gastroenterology: why do we need it and how do we qualify?].
AB  - The rapid scientific progress in the past years has evoked debates about ethical
      limitations of technical innovations. Especially, high-end medicine for patients
      at the end of life gets in the focus of criticism whereas the idea of palliative
      care gains more importance. Gastroenterologists are an important partner in the
      setting of palliative care since many malignant tumors are found in the GI-tract;
      furthermore, about 80 % of all patients with advanced progressive illnesses being
      in a palliative care situation suffer from gastrointestinal symptoms. Vice versa
      the importance of palliative care in gastroenterology is indisputable - in case
      of an unfavourable prognosis the patients may be accompanied until death. A
      return to the core values of medical competence is essential. In this paper, the
      curriculum of "palliative care" in Germany shall be introduced. The aim of this
      work is to explain why it is worthwhile for physicians and especially for
      gastroenterologists to be trained in palliative care.

PMID- 19750432
TI  - [Performance and interpretation of esophageal manometry: recommendations of the
      German Societies for Neurogastroenterology and Motility (DGNM), for Digestive and
      Metabolic Diseases (DGVS) and for General and Visceral Surgery (DGAV)].
AB  - Esophageal manometry examines the pressure profiles of the tubular esophagus and
      of the esophageal sphincters during resting conditions and in response to
      swallowing. It is regarded as the reference method for detection of esophageal
      motility disturbances but, up to date, performance of the procedure is not
      standardized among centers. This review depicts the recommendations of the German
      Societies for Neurogastroenterology and Motility, for Digestive and Metabolic
      Disturbances and for General and Visceral Surgery on indications, performance and
      analysis of conventional esophageal manometry. In addition to concise
      recommendations we give detailed background information so that the article can
      serve as a practical guideline for inexperienced investigators as well as an
      exensive review for the experienced one. Moreover, recommendations on the use of
      newer and/or supplementary diagnostic techniques, that is long-term and high
      resolution manometry as well as esophageal impedance measurements are also given.

PMID- 19750433
TI  - [Summary of the annual meeting of the German Society for Neurogastroenterology
      and Motility].
AB  - The annual meeting of the German Society for Neurogastroenterology and Motility
      was held at Castle Hohenkammer from 27 (th) to 29 (th) of March 2009. A "Young
      Investigator Meeting" took place on Friday communicating basics about scientific
      work. During the two-day main symposium, basic researchers and clinical
      scientists from Germany, but also from Europe, USA, Australia and Egypt presented
      their results on studies of the function of the enteric nerve system,
      gastrointestinal motility, and functional disturbances of the GI tract. Basic
      researchers as well as clinical scientists discussed the study results. Both days
      included a review lecture: E. Muth (USA) talked about "The effects of stress on
      the GI system and its relevance for functional gastrointestinal disorders" and B.
      Niesler (Heidelberg) about "Serotonin receptors and irritable bowel syndrome -
      what are the causal relations?"

PMID- 19750434
TI  - [Hyperglycemia: a risk factor for gastric cancer development?].

PMID- 19750435
TI  - [Osteoporosis pain management].
AB  - Osteoporosis is a chronic disease with an enormous impact on health care costs.
      Approximately 8 Mio. people are affected in Germany. A reasonable part of them is
      suffering from acute and/or chronic pain due to osteoporotic bone fractures and
      musculoskeletal malfunctioning. Therefore, pain therapy is based on the
      principles of acute pain treatment and chronic pain therapy.Drug effects and side
      effects have to be considered with respect to fracture healing, bone mineral
      density and fracture risk.

PMID- 19750436
TI  - [Hyperbaric Oxygenation - utility in intensive therapy - part 1].
AB  - Hyperbaric Oxygenation (HBO) is a medical treatment, in which a patient breathes
      100 % oxygen inside a treatment chamber at a pressure higher than at sea level.
      The indication for HBO has to be considered whenever gas bubbles present in
      tissue or blood circulation (decompression sickness, gas embolism) or when a high
      oxygen delivery is of crucial importance (CO-intoxication, selected anaerobic
      soft tissue infections). HBO must never be considered as a substitute for
      conventional surgical or intensive care therapy, but as an adjuvant of
      (potentially) crucial importance.

PMID- 19750437
TI  - [Legal basis for the hygienic processing of medicinal products].
AB  - The major objectives of the German Medicinal Products Act (Medizinproduktegesetz,
      MPG) and the Medicinal Products Marketing Act (Medizinprodukte
      etreiberverordnung, MPBetreibV) are to avoid the dangers (to health) arising from
      medicinal products (MP). This necessitates procedures for the professional
      maintenance of the, according to regulations low in germs or sterile, MP to be
      used. These procedures are associated with qualified personnel, appropriate
      resources, a reproducibly successful processing procedure and control of the
      technical-unctional safety of the MP.

PMID- 19750438
TI  - [Obesity in pediatric anesthesia].
AB  - The incidence of overweight and obesity in children and adolescents who need an
      anesthesia is increasing. These children have a higher risk for perioperative
      complications. The review discusses definition and causes of obesity in children,
      gives information about relevant pathophysiological changes, and focuses
      anesthesiological management and complications.

PMID- 19750439
TI  - [Anaesthesia management of the obese patient].
AB  - Obesity is a global epidemic, and approximately 20 % of the German population are
      obese. Therefore anaesthesiologists will be increasingly involved in the care of
      obese and morbidly obese patients in the near future. As a prerequisite, the
      hospital must focus on this patient population with respect to facilities and the
      availability of tailored medical equipment and supplies. Comorbidities such as
      diabetes, hypertension, coronary heart disease and sleep apnea considerably
      increase the risk of obese patients. A thorough preoperative evaluation of
      comorbidities, an anaesthesia induction and intraoperative ventilation tailored
      to the pathophysiological sequelae of obesity and a sound knowledge of
      pharmokocinetics are necessary to ensure optimal care for obese patients.

PMID- 19750440
TI  - [Special anaesthesiological requirements in bariatric surgery].
AB  - Obesity is a growing healthcare problem in all industrial countries, which occurs
      with increasing frequency in young people and indicates bariatric surgery.
      Obesity increases the risk for pulmonary and cardiovasculary side effects and
      also the anaesthesiologist is confronted with significantly more problems when
      the patient is overweight and obese. The present review focuses on the surgical
      techniques and the anaesthetic implications of bariatric surgery.

PMID- 19750441
TI  - [The German interdisciplinary taskforce for clinical hemotherapy IAKH and its
      national critical incident reporting system specifically for blood transfusion].
AB  - The German interdisciplinary task force for clinical hemotherapy (IAKH) is an
      independent association of clinicians. It aims for the improvement of blood
      transfusion application processes, procedures and safety in the absence of a
      German hemovigilance system. Whereas the producers of blood products concentrate
      on product safety, the IAKH focuses on administrative needs such as forms and
      regulations associated with the administration of blood products. It provides
      information about coagulation disorders, autologous blood donation and cell
      saving as well as techniques that reduce the amount of allogeneic transfusion
      needs. Benefits of a membership in IAKH are electronic and individual
      recommendations to clinical hemotherapy issues, an exchange forum, as well as low
      cost participation at conventions and meetings. Just recently, a critical
      incident reporting system for errors in blood transfusion and hemotherapy was
      launched (www.iakh.de/ BeinaheFehlerErfassung/). The entries reported are
      analyzed, feedback and recommendations are given. Everybody in contact with the
      administration of blood products is asked to report errors and critical
      incidents.

PMID- 19750442
TI  - [Incidence and mechanism of injuries in cable-wakeboarding: a prospective study].
AB  - Cable-wakeboarding has become more and more popular in the last years in Germany
      and worldwide as well. The mechanism, frequency and severity of injuries is still
      unclear and not described in the literature yet. Thus to compare the injuries of
      cable-wakeboarding with similar sports we decided to perform this prospective
      study during a six months summer season. The study included 122 actives with a
      mean age of 25 years (15 - 42, +/- 5.876), 81,1 % male, sending an online
      questionnaire to us every month. 98 % of the participants suffered 277 injuries
      during 8647 hours of activity, 108 (39 % 12 / 1000 h) had to be treated
      medically. We found out most frequently mild injuries (61 % 19.5 / 1000 h), 15 %
      very severe injuries (4.8 / 1000 h), 14 % severe injuries (4.5 / 1000 h) and 10 %
      medium-severe injuries (3.2 / 1000 h). Injuries of the knee and the shoulder
      dominated in more than 20 % each with more than 70 % distorsions and contusions.
      CONCLUSION: Cable-wakeboarding is not more dangerous in regard to injuries than
      similar trendy sports even though the rate of mild injuries not treated medically
      is quite higher.

PMID- 19750443
TI  - [The impact of different sports on posture regulation].
AB  - BACKGROUND: Previous work has suggested that both the level of activity and the
      type of sport may have a major impact on postural control. However, no systematic
      investigation has been performed regarding the various types of professional
      sports. Particularly, the impact of competitional sports on the postural
      subsystems has not been elucidated so far. OBJECTIVE: The aim of this study was
      to investigate the influence of the major professional sport types, such as
      handball, gymnastics, swimming, and shooting, on the subsystems of postural
      control. We also tested the hypothesis that specific types of sport have specific
      effects on postural regulation. METHODS: 155 competitive male and female athletes
      (handball: n = 30; gymnastics: n = 44; swimming: n = 50; shooting: n = 31), and
      34 age- and gender-matched controls were investigated using the Interactive
      Balance System (IBS; Tetrax Inc., Ramat Gan, Israel). The following spectral and
      time-domain indices were determined: power in the following frequency bands:
      P(F1) (0.03 - 0.1 Hz), P(F)(2 - 4) (0.1 - 0.5 Hz), P(F)(5 - 6) (0.5 - 1.0 Hz),
      P(F)(7 - 8) (> 1.0 Hz), stability index (STABI), and synchronisation index (SYN).
      RESULTS: Shooting athletes exhibited significantly smaller values of P(F1) (p =
      0.003), P(F)(2 - 4) (p < 0.001), and P(F)(7 - 8) (p = 0.002), respectively, than
      the other athletes investigated. Also, the shooting athletes exhibited the
      smallest STABI values (p = 0.002). In contrast, the gymnasts showed the largest
      SYN values (p = 0.002). CONCLUSIONS: Different types of competitive sports exert
      different effects on the various subsystems of posture control, where especially
      shooting competitors demonstrate a significantly better posture regulation. Those
      effects can be parameterised and quantified with the IBS which thus enables an
      efficient and purposeful training. Furthermore, the IBS is highly suitable for
      aptitude screening in sports with high posture regulatory demands (shooting
      competitions, gymnastics, diving etc.).

PMID- 19750444
TI  - [Osteoathritis after SLAP Lesion? Clinical and arthro-MRI evaluation after
      arthroscopic SLAP refixation].
AB  - INTRODUCTION: The development of glenohumeral osteoarthritis is sufficiently
      described after instability and rotator cuff pathologies. The purpose of this
      work was to evaluate a coherency between glenohumeral osteoarthritis and SLAP
      lesions by means of MR arthrography which has not been described up to now in the
      literature. MATERIAL AND METHODS: 20 patients with a SLAP lesion type II were
      treated with arthroscopic SLAP repair. MR arthrography was performed after intra
      articular administration of diluted gadolinium (after positive vote of the ethics
      committee) after a mean FU of 36 months (26 to 54 months). The MR arthrography
      data were analysed by 3 investigators (two radiologists, one orthopaedic surgeon)
      in consensus. Osteoarthritis was graded according to the modified Outerbridge
      classification for MRI. Besides image quality and artifacts, adhesions from the
      tendon to the bone and the rotator cuff were evaluated. Intraoperative documented
      findings were used for comparison. The clinical investigation encompassed Roweand
      Constant score, clinical investigation of instability and SLAP lesion (O'Brian
      test, SLAP apprehension test) as well as the subjective contentment. The
      statistical evaluation was performed with SAS reverse. RESULTS: In 12 of 20 cases
      an increase of glenohumeral osteoarthritis was seen, in 4 cases a circumscribed
      entire cartilage defect appeared in the MRI. Osteoarthritis did not correlate
      with the subjective and objectively collected clinical results or the aetiology
      of the SLAP lesion at the time of the re-examination. Results of the MR
      arthrography revealed that, in six cases, the biceps anchor did not show proper
      bony ingrowth. Nonetheless, these cases do not correlate with a poorer clinical
      result. CONCLUSION: Due to the small case number a correlation between SLAP
      lesion and osteoarthritis cannot be postulated statistically, however, the
      results still indicate a trend which should be pursued in the long-term course.

PMID- 19750445
TI  - [The operative treatment of rhizarthrosis for patients with extreme exposure of
      the hand by athletic activities--is the trapeziectomy with interposition of an
      pyrocarbon spacer a option for treatment?].
AB  - PURPOSE: The rhizarthrosis is the most common degenerative joint disease of the
      hand. Incidence is detected around 10 %. For the treatment of rhizarthrosis
      different conservative and surgical methods are available. As many publications
      deal with the outcome of different surgical procedures. However there are no
      experiences in possibility of resuming an extreme exposure of the hand by
      athletic activities and the relevant timeframe between surgical treatment and the
      resumption as well as which of the competing surgical procedures you should
      suggest the patient. CASE REPORT: A female 46-year-old tennis player went to
      hospital in January 2005 with rhizarthrosis in stage 3 according to Eaton of the
      dominant right hand with pain during rest and exertion in the right basal joint.
      She was treated with trapeziectomy and interposition of a pyrocarbon spacer.
      Since the last clinical and radiological check in spring 2009, the patient is
      completely free of complaints and has resumed to play tennis 1 - 2 hours per day
      at tournament level. The correct position of the pyrocarbon spacer is
      radiologically verified while the joint space in the carpo-metacarpal joint is
      constant. CONCLUSION: The trapeziectomy with interposition of an pyrocarbonspacer
      is a worthfull alternative compared to other established operative techniques.
      The demonstrated casuistic proves that this treatment matches both the high and
      multiaxial stress on the first ray of athletes. Four dislocations in the examined
      collective and the price of the implant of 930 Euro has to be discussed
      critically.

PMID- 19750446
TI  - [Exertional compartment syndrome of the lower leg and common peroneal nerve palsy
      as combined injury after weight lifting].
AB  - While the compartment syndrome after traumatic injury is a well-known entity and
      well recognised, an exercise-induced acute compartment syndrome is seldom and
      often missed. Delayed diagnosis and treatment can result in a poor outcome such
      as loss of function or limb. Early recognition and prompt fasciotomy are
      necessary. We would like to present the case of an exertional compartment
      syndrome of the tibialis anterior space after weight-lifting which was
      complicated by an acute pressure-induced palsy of the common peroneal nerve due
      to a self applied knee-support-bandage. A thorough case history provided the clue
      to understand the resulting pathology. This case shows again the necessity of
      good medical assistance for athletes in leisure-time sport activities.

PMID- 19750447
TI  - Effective "short" double-balloon enteroscope for diagnostic and therapeutic ERCP
      in patients with altered gastrointestinal anatomy: a large case series.
AB  - BACKGROUND AND STUDY AIMS: Although endoscopic retrograde
      cholangiopancreatography (ERCP) is technically challenging in patients with
      altered gastrointestinal anatomy, a double-balloon enteroscope (DBE) permits
      examinations of a much longer segment of the small bowel than does a standard
      endoscope, and may be used to perform ERCP in such patients. Since only limited
      accessories are available for a conventional DBE, we performed ERCP with a
      "short" DBE, which has a 2.8-mm working channel and a 152-cm working length and
      for which conventional accessories are available, in patients with altered
      gastrointestinal anatomy, and evaluated this alternative technique. PATIENTS AND
      METHODS: In 68 patients with a Roux-en-Y total gastrectomy (n = 36), Billroth II
      gastrectomy (n = 17), or pancreatoduodenectomy (n = 15), ERCP (103 procedures)
      was performed with a "short" DBE. RESULTS: Deep insertion was successful in
      100/103 procedures (97 %). Cholangiogram was successfully obtained in 98/100
      procedures (98 %). Treatment was accomplished in all 98 procedures in which a
      cholangiogram was obtained (100 %). Therapeutic interventions including stone
      extraction (n = 47), nasobiliary drainage (n = 38), stent placement (n = 36),
      sphincterotomy (n = 31), choledochojejunostomy dilation (n = 29), tumor biopsy (n
      = 10), and naso-pancreatic duct drainage (n = 1) were performed successfully.
      Complications occurred in 5/103 procedures (5 %), all in patients with Roux-en-Y
      reconstruction. CONCLUSIONS: Despite the relatively high rate of complications
      seen in patients with Roux-en-Y reconstruction, ERCP with a "short" DBE is
      effective in patients who have undergone bowel reconstruction.

PMID- 19750448
TI  - Endoscopic mucosal resection for large and giant sessile and flat colorectal
      polyps: a single-center experience with long-term follow-up.
AB  - BACKGROUND AND STUDY AIMS: This study examines efficacy, outcome, and
      complications of endoscopic mucosal resection (EMR) for large (> or = 20 mm) and
      giant (> or = 40 mm) sessile and flat colorectal polyps. PATIENTS AND METHODS:
      All EMRs carried out at our institution over a 9-year period, for large and giant
      sessile and flat colorectal polyps with an intensive and regular follow-up were
      evaluated. The rate of en bloc and piecemeal resection, complications, and
      recurrence were analyzed. RESULTS: A total of 148 polyps were resected in 148
      patients. There were 113 large polyps (76.3 %) with a mean size of 25 +/- 4.7 mm
      (range 20 - 39 mm) and 35 giant polyps (23.7 %) with a mean size of 48.8 +/- 12.5
      mm (range 40 - 100 mm). The most frequent location was the rectum, occurring in
      43.2 %. All lesions were removed in a single session. En bloc resection was
      performed in 65 cases (43.9 %) and piecemeal in 83 (56.1 %). Procedural bleeding
      occurred in 13 EMRs (8.8 %), and one case of early and one case of delayed
      bleeding also occurred. There were two cases of postpolypectomy syndrome and one
      case of perforation. Malignancy (intramucosal and invasive cancer) was mostly
      present in polyps with sessile shape ( P = 0.0013). Follow-up colonoscopy was
      performed in 142 patients for a mean of 29.8 months. Recurrence was observed in
      6/142 (4.2 %) patients and was found more in patients with giant polyps ( P =
      0.014). CONCLUSIONS: In our experience EMR is a simple and safe procedure for
      removing large and giant sessile and flat colorectal polyps, and is associated
      with a very low risk of complication and local recurrence.

PMID- 19750449
TI  - Reflux disease and Barrett's esophagus.

PMID- 19750450
TI  - Endoscopic retrograde cholangiopancreatography (ERCP).

PMID- 19750451
TI  - Fulminant metastatic spread in a patient with an early gastric cancer.
AB  - A patient with an early gastric cancer was treated initially by endoscopic
      submucosal dissection (ESD) at our hospital. The resected specimen showed a depth
      of submucosal infiltration of more than 500 microm. Therefore, in accordance with
      the extended criteria with regard to EMR, the patient underwent gastrectomy. The
      TNM stage was pT1 (sm3), pN0 (0 / 58), cM0, L0, V0, G2 after surgery (UICC stage
      Ia). At 3 months later ultrasound revealed a new mass in the liver, and biopsy
      showed a rapidly growing metastasis of the gastric adenocarcinoma. Finally,
      immunohistochemical analysis of all the lymph nodes of the resected stomach
      revealed a micrometastasis (3mm) directly under the ESD site. The patient died 6
      months later. This clinical case highlights the risk of affected lymph nodes in
      early gastric cancer and the consequent risk of metastasis which increases with
      greater depth of infiltration to the submucosa.

PMID- 19750452
TI  - Techniques to facilitate ERCP with a conventional endoscope in patients with
      previous pancreatoduodenectomy.
AB  - There is little guidance on the performance of endoscopic retrograde
      cholangiopancreatography (ERCP) in patients with previous pancreatoduodenectomy.
      We reviewed techniques for ERCP with a conventional endoscope and assessed its
      value in 10 patients with previous pancreatoduodenectomy (15 ERCPs). After
      exploration of the surgical reconstruction, we used a front-viewing endoscope,
      and we used a small firm pillow under the abdomen and hand compression for
      preventing loop formation. Successful insertion to the ductal anastomoses and
      biliary cannulation were achieved in 13 / 15 procedures (87 %). In 6 procedures
      where we attempted pancreatic cannulation, we could not identify the
      pancreatojejunostomy, but after spraying contrast around the suspected location
      of the ductal anastomosis we obtained a pancreatogram in 4 / 6 procedures (67 %).
      Endoscopic biliary interventions were successful in 6 / 7 procedures (86 %). No
      complications were encountered. Use of appropriate techniques makes ERCP with a
      conventional endoscope feasible, effective, and safe in patients with previous
      pancreatoduodenectomy. Endoscopic therapy can be performed successfully in the
      bile duct, but has limited value regarding the pancreatic duct.

PMID- 19750453
TI  - Is bacteriologic surveillance in endoscope reprocessing stringent enough?
AB  - Endoscopes, including duodenoscopes, are medical devices that are frequently
      associated with outbreaks of nosocomial infections. We investigated an outbreak
      of multidrug-resistant PSEUDOMONAS AERUGINOSA sepsis affecting three patients
      after endoscopic retrograde cholangiopancreaticography (ERCP). Epidemiologic
      investigation supplemented by molecular typing revealed that one ERCP scope was
      the source of infection with P. AERUGINOSA. No contamination with this
      microorganism was found after screening of washer-disinfectors, connecting tubes,
      and environmental surfaces in the endoscopy center. PSEUDOMONAS isolates from
      blood and endoscope channels before gas sterilization with ethylene oxide (ETO)
      were characterized by molecular typing as "linked isolates". Though the current
      surveillance system did not prevent the infections in three patients, our
      microbiological surveillance protocol with routine culturing of endoscopes was
      helpful in detecting the source of contamination and probably avoided numerous
      cross-contaminations in other patients who underwent ERCP procedures with
      endoscopes.

PMID- 19750454
TI  - Therapeutic pancreatic endoscopy after Whipple resection requires rendezvous
      access.

PMID- 19750455
TI  - Possible importance of increased intra-abdominal pressure for the development of
      necrotizing enterocolitis.
AB  - BACKGROUND/PURPOSE: Despite extensive clinical and laboratory investigations,
      many aspects of the pathogenesis of necrotizing enterocolitis (NEC) remain
      unclear. In the present work we describe 5 neonates with NEC in whom intra
      abdominal pressure (IAP) was measured to investigate the potential role of
      abdominal compartment syndrome (ACS) in the development of NEC and to correlate
      the severity of NEC with the value of IAP. METHODS: IAP pressure was determined
      in two groups - Group A consisting of five patients without NEC (Control) and
      Group B consisting of five patients who developed NEC - by measuring the urinary
      bladder pressure (UBP). The correlation between increased IAP and severity of
      NEC, complications of NEC and indications for surgery was investigated. RESULTS:
      In four patients from Group B, the general condition deteriorated despite
      aggressive supportive treatment, and a laparotomy was performed. These neonates
      demonstrated a significant increase (compared to Control patients) in UBP (9.0+/
      2.5 vs. 4.8+/-1.4 mmHg, p=0.001), which increased progressively with exacerbation
      of NEC and reached a peak value of 13.3+/-2.4 mmHg before operation. The elevated
      IAP was accompanied by hemodynamic instability in all patients, respiratory
      instability in 3 patients and decreased urinary output in one patient. One
      patient remained unstable and died 6 h after operation. In the fifth patient from
      Group B, intestinal obstruction developed two weeks after NEC and did not result
      in increased IAP. CONCLUSIONS: Our results suggest that IAP is associated with an
      exacerbation of NEC. Thus, this study provides further information which may
      improve our understanding of the pathogenic process of NEC.

PMID- 19750456
TI  - Endoloop closure of the urinary bladder is safe and efficient in female piglets
      undergoing transurethral NOTES nephrectomy.
AB  - INTRODUCTION: Recently, we showed that various procedures for rigid Natural
      Orifice Transluminal Endoscopic Surgery (NOTES) can be successfully performed in
      piglets. However, the safety and effectiveness of endoscopic closure of the
      urinary bladder remains to be determined before introducing transurethral NOTES
      in children. Our study was designed to investigate the safety and impermeability
      of the urinary bladder after endoscopic closure in transurethrally assisted
      nephrouretectomy in piglets. MATERIAL AND METHODS: Five female piglets (mean
      weight 14.5 kg; range: 14-15) underwent right-sided transurethral
      nephroureterectomy using a hybrid technique with one 15 mm trocar placed
      umbilically and one 3 mm trocar placed transvesically. Hilar dissection was
      performed with a 5 mm Endoligasure vessel sealing device. After umbilical
      retrieval of the resected kidney, the urinary bladder was closed by an Endoloop
      via an umbilical "two in one system" with the assistance of a 2 mm
      transurethrally placed endoscopic clamp. Endpoints of the study were total
      operation time, duration of cystoscopy and transurethral trocar positioning,
      duration of nephrectomy, duration of bladder closure and determination of bladder
      impermeability. Intraoperatively, bladder filling was performed with normal
      saline (ml), while bursting pressure (mmHg) was measured by filling the harvested
      bladder with air. RESULTS: All nephroureterectomies were successfully performed
      with negligible blood loss. Mean total operation time was 46 min (range: 35-69).
      Cystoscopy and transurethral trocar positioning took 14 min (range: 9-23), and
      nephrectomy took 28 min (range: 18-48). Mean duration of bladder closure was 4
      min (range: 2-6). Mean volume of intraoperative bladder filling was 94 ml (range:
      80-100), indicating adequate capacity after closure with Endoloops. Post-mortem
      bladder impermeability was confirmed by a mean air filling bursting pressure of
      88 mmHg (range: 70-140) indicating sufficient bladder closure. CONCLUSION: A safe
      urinary bladder closure is mandatory for transurethral rigid NOTES procedures and
      can be adequately achieved with Endoloops.

PMID- 19750457
TI  - Nipple pain at presentation predicts success of tongue-tie division for
      breastfeeding problems.
AB  - INTRODUCTION: In mother-infant pairs experiencing breastfeeding difficulties,
      frenulotomy for tongue-tie may improve breastfeeding. We tested the hypothesis
      that those experiencing nipple pain are most likely to benefit from the procedure
      in a prospective cohort study. MATERIALS AND METHODS: Mother-infant pairs
      attending a dedicated clinic for the assessment and treatment of tongue-tie
      completed a standardised, structured symptom questionnaire. Three months later
      outcome was assessed by questionnaire. Multivariate logistic regression analysis
      was used to determine preoperative predictors of successful outcome. RESULTS:
      Sixty-two infants <90 days old underwent frenulotomy and completed follow-up. At
      presentation, 52 mothers (84%) reported nipple pain, and 32 mothers (52%) nipple
      trauma. Three months after frenulotomy, 78% of respondents were still
      breastfeeding. Feed lengths (mean reduction: 17 mins; p<0.001) and time between
      feeds (mean increase: 38 mins; p<0.001) had significantly improved, as had
      difficulty of feeding (mean improvement in self-rated difficulty score: 42%;
      p<0.001). Those having difficulty breastfeeding due to nipple pain showed a
      significant long-term benefit from frenulotomy; pre-frenulotomy nipple pain was
      associated with an increased likelihood of breastfeeding at 3 months in adjusted
      multivariate analysis (OR 5.8 [95% CI 1.1-31.6]). CONCLUSION: Mother-infant pairs
      with tongue-tie and breastfeeding difficulties due to nipple pain are most likely
      to benefit from frenulotomy.

PMID- 19750458
TI  - Endoscopic ultrasound with fine-needle aspiration facilitates diagnosis of
      metastatic iliac lymph node invasion in prostate cancer.

PMID- 19750459
TI  - [Early health promotion and prevention at the beginning of the 20th and 21st
      centuries. Data and thoughts on the 100th anniversary of the opening of the
      Empress Auguste Victoria House in Berlin].
AB  - In June 1909, The Empress Auguste Victoria House in Berlin was opened. This first
      institute for preventive paediatrics had the objective to overcome infant
      mortality in Germany. This objective was attained. Since then, an unprecedented
      decrease of mortality in all age groups occurred as well as a doubling of life
      expectancy. With this "retreat of death", our concepts of health changed
      fundamentally, and a new spectrum of diseases emerged. This article discusses
      some mile stones of this change, and explains why we find more illness despite
      the great improvement in the field of health. The "new diseases" amenable to
      early prevention are presented in a table. To make disease prevention successful
      requires the participation of the individual. Therefore, it is important to know
      the demand to make a good programme effective in the population. Empirical
      results of a nationwide representative study on the demand by expecting and young
      parents for preventive consultation are presented. Anticipatory guidance of young
      parents is a modern approach to health promotion and disease prevention. A
      controlled trial shows that this approach improved knowledge, behaviour, health
      risk indicators, health, and development during the first two years after
      delivery. Future studies should focus on long term effects of early health
      promotion.

PMID- 19750460
TI  - [Transfer of the AGnES concept to the regular German health-care system: legal
      evaluation, reimbursement, qualification].
AB  - INTRODUCTION: According to an amendment of German social security legislation,
      the AGnES concept of delegation of certain tasks of medical care, especially
      house calls, by general practitioners (GPs) to qualified practice employees
      (AGnES employees), will be transferred into the regular German health care system
      from January 2009 onward. The concept was developed to support GPs in regions
      with imminent gaps in primary care. METHODS: Patient data, the specifically
      delegated and all other activities carried out by the AGnES employees in the
      AGnES projects were digitally documented. Additionally, the participating GPs,
      AGnES employees and patients underwent a set of standardised interviews. A
      curriculum to qualify the AGnES employees and to define the requirements needed
      was developed. A legal assessment of all delegated activities was carried out,
      and an economical model to calculate the necessary allowance was calculated.
      RESULTS: In seven model projects in four federal states in Germany, 11,228 house
      calls were carried out involving 1,424, mostly multimorbid, patients (mean age:
      78.6 years). A modular structured curriculum, considering the basic education and
      acquired competences, was developed. It allows for an individual qualification of
      the AGnES employees. The result of the legal assessment was the central relevance
      of the qualification of the practice employees according to the AGnES curriculum
      as the essential condition for carrying out the entire range of activities of the
      AGnES concept. The economic model revealed euro 21.58 for a house call by an
      AGnES employee. The underlying model referred to underserved regions. CONCLUSION:
      A successful transfer of the AGnES concept with a high standard of quality into
      regular health-care depends on several factors. Of particular importance is the
      specific qualification of the practice employees, which is a central legal
      condition for the delegation of medical tasks from GPs to AGnEs employees. A
      second determining factor is also an adequate reimbursement within the catalogus
      of the statutory health insurances.

PMID- 19750461
TI  - Primary sinonasal tuberculosis in a Nigerian woman presenting with epistaxis and
      proptosis: a case report.
AB  - Tuberculosis is the second leading cause of death worldwide after human
      immunodeficiency virus/AIDS and is especially prevalent in developing countries.
      We report a case of primary sinonasal tuberculosis without pulmonary involvement,
      which is rare, in a 27-year old female Nigerian fish farmer. She had a 3-year
      history of right-eye proptosis, bilateral nasal masses, and epistaxis. Cranial
      computed tomography suggested an extensive sinonaso-orbital neoplastic lesion. We
      performed a right external frontoethmoidectomy. Histologically, the excised nasal
      polyps revealed tuberculosis. Six months of antituberculosis therapy provided
      satisfactory improvement. Sinonasal tuberculosis, despite its rarity, should be
      added to the differential diagnosis of nasal and paranasal sinus disorders, and
      histologic evaluation remains the hallmark of diagnosis. Therapy with a short
      duration, multidrug combination, rather than the longer-duration treatment
      regimen hitherto used, could be quite valuable, especially in the setting of a
      developing country with poor patient compliance.

PMID- 19750462
TI  - Parathyroid carcinoma: a rare cause of primary hyperparathyroidism.
AB  - Most cases of primary hyperparathyroidism (80 to 90%) are caused by a parathyroid
      adenoma; most of the rest are caused by either parathyroid gland hyperplasia or
      multiple adenomas. Parathyroid carcinoma can be the cause of primary
      hyperparathyroidism in 1 to 5% of patients. When the appropriate clinical
      scenario is presented, it must be considered in the differential diagnosis. We
      describe the case of a 72-year-old woman with a long history of hypercalcemia and
      arthritic shoulder and neck pain who was admitted with an elevated calcium level
      and acute renal failure secondary to bilateral obstructing ureteral calculi. A
      sestamibi scan and magnetic resonance imaging detected the presence of what
      appeared to be a right inferior parathyroid adenoma. Her intact parathyroid
      hormone (PTH) level was 2,257 pg/ml. Following placement of bilateral ureteral
      stents and adequate hydration, the patient was taken to the operating room for a
      neck exploration and removal of a parathyroid adenoma with rapid intraoperative
      PTH monitoring. A 4 x 2.5-cm, 10-g mass was removed from the right inferior pole
      of the thyroid gland. Following excision, her intraoperative PTH level dropped
      from 1,103 to 110 pg/ml. Her ionized calcium levels fell from a high of 8.4 mg/dl
      preoperatively to 4.7 mg/dl. On final pathologic examination, the mass was
      confirmed to be a parathyroid carcinoma.

PMID- 19750463
TI  - Bean sprout impaction in the pharynx: two cases of this unusual foreign body.
AB  - We report 2 cases of bean sprout impaction in the pharynx. To the best of our
      knowledge, pharyngeal impaction of a bean sprout has not been previously
      described in the literature. We also comment on the theoretical infective risks
      associated with the long-term impaction of organic foreign bodies and the
      validity of a thorough ENT examination, even when the foreign body appears to be
      insignificant.

PMID- 19750464
TI  - A case of nasogastric tube perforation of the nasopharynx causing a fatal
      mediastinal complication.
AB  - Iatrogenic nasopharyngeal perforations secondary to improper nasogastric tube
      insertion probably occur more frequently than has been reported. Our review of
      the literature found very few cases. We report the case of a 79-year-old woman
      who died of mediastinal complications following the improper insertion of a
      nasogastric tube that resulted in a nasopharyngeal perforation. We also review
      the proper technique for inserting these tubes.

PMID- 19750465
TI  - Expect the unexpected: two cases of penetrating head and neck trauma from
      Operation Iraqi Freedom.
AB  - The protocol for treating penetrating head and neck trauma in a war zone differs
      from the standard protocol. Rather than first securing an airway, as is standard
      in civilian trauma cases, the primary emphasis is on assessing and controlling
      hemorrhage because it is the leading cause of morbidity and mortality in a
      battlefield setting. Once that has been addressed, we shift to standard advanced
      trauma life-support protocols. We describe two cases we encountered at our
      combined medical clinic in Western Baghdad--one involving a 4-year old Iraqi
      child with an ammunition round lodged in her neck and one involving a 38-year-old
      female U.S. soldier with a round lodged in her right superolateral orbit. Both
      cases were transferred to combat support hospitals for further treatment after
      our initial assessment and treatment, and both had successful outcomes.

PMID- 19750466
TI  - Tympanum-canal angles anteriorly, anteroinferiorly, and inferiorly: a postmortem
      study of 41 adult crania.
AB  - The angles formed by the tympanic membrane and the external ear canal anteriorly,
      anteroinferiorly, and inferiorly can pose surgical challenges, and the spaces
      they form can harbor iatrogenic cholesteatoma. The range of values previously
      reported for these angles--27 degrees to 60 degrees--seems not to have been
      determined in a clinically applicable manner. To clinically describe the tympanum
      canal angles, assess bilateral symmetry, assess the angles relative to mastoid
      pneumatization, and assess the relationship of the angles to manubrium
      orientation in the skull, the author conducted a postmortem anatomic study of 41
      bequeathed adult crania without clinical otitis media. As viewed through the
      external ear canal, the tympanum-canal angles were measured in 10 degrees
      increments anteriorly, anteroinferiorly, and inferiorly relative to the line of
      the manubrium. Mastoid sizes were determined radiographically. In the right ear,
      the tympanum-canal angles ranged from 40 degrees to 60 degrees anteriorly
      (median: 55 degrees), from 50 degrees to 70 degrees anteroinferiorly (median: 60
      degrees), and from 70 degrees to 80 degrees inferiorly (median: 75 degrees).
      Bilateral symmetry was found (each rs > or = 0.69, p < 0.001). Although the
      angles did not correlate with either mastoid pneumatization or manubrium
      orientation relative to the Frankfort plane, nonvisualization of the annulus
      anteriorly was significantly more common in specimens with well-pneumatized
      mastoids (p < 0.05). The author concludes that the tympanum-canal angles
      anteriorly, anteroinferiorly, and inferiorly have comparatively narrow ranges,
      exhibit bilateral symmetry, and are unrelated to both mastoid size and manubrium
      orientation in the skull.

PMID- 19750467
TI  - Pyogenic granuloma of the hard palate: a case report and review of the
      literature.
AB  - We describe the case of a 35-year-old man who presented with a 4 x 4-cm ulcerated
      swelling over the hard palate that had progressed over 6 months. The lesion was
      associated with recurrent bleeding and occasional pain. Based on the lesion's
      clinical appearance and other characteristics (i.e., the slow progression,
      ulceration, and lack of regional lymphadenopathy), a provisional diagnosis of
      pyogenic granuloma was made, even though pyogenic granulomas of such size are
      rare. The mass was excised via a transoral route with a 0.5-cm margin of healthy
      mucosa, and the base was curetted. Histopathologic examination of the excised
      specimen confirmed the diagnosis. We discuss the etiopathogenesis of this entity
      and the various treatment options, and we review the relevant literature.

PMID- 19750468
TI  - Chondrocalcinosis of the temporomandibular joint: a rare but important diagnosis.
AB  - Patients with preauricular masses present with a wide range of pathologies, the
      most common of which are neoplasms of the parotid gland, metastatic or
      inflammatory disease, and enlarged periparotid lymph nodes. Other possibilities
      include lesions that arise from the skull base or the temporomandibular joint
      (TMJ). Chondrocalcinosis is a common age-related phenomenon that has a
      predilection for fibrocartilage. Although it can involve any joint, the knee is
      by far the most common site; involvement of the TMJ is very rare. We describe a
      case of chondrocalcinosis of the TMJ that manifested as a preauricular swelling
      and mimicked a parotid tumor, and we discuss the pathophysiology and radiographic
      characteristics of this disease.

PMID- 19750469
TI  - Fellowship training in otolaryngology.

PMID- 19750470
TI  - Fistulography: a useful imaging modality for identifying the exact location and
      extent of complete branchial fistulas.

PMID- 19750471
TI  - Applebaum incudostapedial prosthesis.

PMID- 19750472
TI  - Ophthalmology microscalpel for super-sharp skin edges.

PMID- 19750473
TI  - Pathology Clinic. Kikuchi-Fujimoto disease.

PMID- 19750474
TI  - Partial esophageal obstruction from anterior cervical spine hardware.

PMID- 19750475
TI  - Osseous metaplasia of the maxillary sinus with formation of a well-developed
      haversian system and bone marrow.
AB  - Osteogenesis in the maxillary sinus is a lesser known entity in otolaryngology,
      although it is put to good therapeutic use by maxillofacial surgeons. We present
      a case of postoperative osseous metaplasia in the maxillary sinus that led to the
      formation of mature bone with a well-developed haversian system and bone marrow.
      Such a finding has not been previously reported as a complication of endoscopic
      sinus surgery. This case highlights the importance of keeping in mind the
      possibility of osteogenesis within the maxillary sinus in patients who experience
      a recurrence of symptoms following sinus surgery.

PMID- 19750476
TI  - Intraoperative bupivacaine for reduction of post-tonsillectomy pain: a
      randomized, placebo-controlled, double-blind study of 26 patients.
AB  - We conducted a randomized, controlled, double-blind, prospective study to
      evaluate the effect of intraoperative bupivacaine injection on postoperative pain
      control following Bovie cautery-assisted tonsillectomy in 26 adults. Sixteen
      patients were injected with 10 ml of 0.5% bupivacaine with 1:200,000 epinephrine,
      and 10 were injected with 10 ml of normal saline solution. For 10 days after
      surgery, patients completed a questionnaire to rate their overall pain and to
      record their narcotic consumption and oral intake. At study's end, there was no
      statistically significant difference in pain scores, narcotic use, and oral
      intake between the bupivacaine group and the controls (p = 0.13, 0.37, and 0.35,
      respectively). We conclude that the effects of perioperative bupivacaine on
      postoperative pain control in tonsillectomy patients are similar to those of
      placebo.

PMID- 19750477
TI  - Yeast Ste23p shares functional similarities with mammalian insulin-degrading
      enzymes.
AB  - The S. cerevisiae genome encodes two M16A enzymes: Axl1p and Ste23p. Of the two,
      Ste23p shares significantly higher sequence identity with M16A enzymes from other
      species, including mammalian insulin-degrading enzymes (IDEs). In this study,
      recombinant Ste23p and R. norvegicus IDE (RnIDE) were isolated from E. coli, and
      their enzymatic properties compared. Ste23p was found to cleave established RnIDE
      substrates, including the amyloid-beta peptide (Abeta1-40) and insulin B-chain. A
      novel internally quenched fluorogenic substrate (Abz-SEKKDNYIIKGV-nitroY-OH)
      based on the polypeptide sequence of the yeast P2 a-factor mating propheromone
      was determined to be a suitable substrate for both Ste23p and RnIDE, and was used
      to conduct comparative enzymological studies. Both enzymes were most active at 37
      degrees C, in alkaline buffers and in high salt environments. In addition, the
      proteolytic activities of both enzymes towards the fluorogenic substrate were
      inhibited by metal chelators, thiol modifiers, inhibitors of cysteine protease
      activity and insulin. Characteristics of STE23 expression were also evaluated.
      Our analysis indicates that the 5' terminus of the STE23 gene has been
      mischaracterized, with the physiologically relevant initiator corresponding to
      residue M53 of the publicly annotated protein sequence. Finally, we demonstrate
      that, unlike haploid-specific Axl1p, Ste23p is expressed in both haploid and
      diploid cell types. Our study presents the first comprehensive biochemical
      analysis of a yeast M16A enzyme, and provides evidence that S. cerevisiae Ste23p
      has enzymatic properties that are highly consistent with mammalian IDEs and other
      M16A enzymes.

PMID- 19750478
TI  - Alloantigen-specific de novo-induced Foxp3+ Treg revert in vivo and do not
      protect from experimental GVHD.
AB  - Induced antigen-specific Foxp3(+) T cells (iTreg) are being discussed as a
      promising alternative to polyclonal natural Foxp3(+) T cells (nTreg) for cell
      based therapies, particularly to achieve transplantation tolerance. Using
      Foxp3eGFP-reporter mice, we here establish an efficient protocol to induce and
      expand alloantigen-specific iTreg from Foxp3(-)CD4(+) T cells with cluster
      disrupted DC. These iTreg were mainly CD62L(+) and showed efficient suppressive
      activity in vitro. However, in contrast to nTreg, adoptively transferred iTreg
      entirely failed to prevent lethal graft versus host disease (GVHD). Within
      irradiated recipients, the majority of adoptively transferred Foxp3(+) iTreg, but
      not Foxp3(+) nTreg quickly reverted to Foxp3(-)CD4(+) T cells. We therefore
      suggest that therapeutic approaches to treat GVHD should rely on nTreg, whereas
      the use of de novo alloantigen-induced iTreg should be handled with caution since
      the stability of the regulatory phenotype of the iTreg could be of major concern.

PMID- 19750479
TI  - IL-33 promotes DC development in BM culture by triggering GM-CSF production.
AB  - Short-term DC cultures generated with GM-CSF and other cytokines have markedly
      improved our ability to study the immunobiology of DC. Here, we tested 65
      cytokines individually for their potential to promote the generation of CD11c+
      cells in a murine BM culture system. In addition to several cytokines known to
      promote DC survival and/or growth, IL-33 was found to augment DC development time
      and dose-dependently. Although the resulting CD11c+ cells generated in the
      presence of IL-33 exhibited a typical dendritic morphology, they expressed MHC
      class II molecules only at modest levels, showed negligible responses to TLR
      ligands, produced no detectable IL-12 p70, displayed PD-L1 and PD-L2 on the
      surface, and failed to activate immunologically naive T cells efficiently. IL-33
      induced expansion of CD11c+ cells was completely blocked by anti-GM-CSF mAb, and
      GM-CSF mRNA and protein expression in BM culture was markedly elevated by added
      IL-33, indicating that IL-33 promotes in vitro DC generation indirectly by a GM
      CSF-dependent manner. With regard to the cellular source, IL-33-dependent GM-CSF
      production was observed exclusively within the CD45+/FcepsilonRI+ BM population.
      Not only do our results reinforce the notion that GM-CSF serves as a primary DC
      growth factor, but they also reveal a previously unrecognized mechanism
      supporting DC development.

PMID- 19750481
TI  - Cathepsin X cleaves the beta2 cytoplasmic tail of LFA-1 inducing the intermediate
      affinity form of LFA-1 and alpha-actinin-1 binding.
AB  - The motility of T cells depends on the dynamic spatial regulation of integrin
      mediated adhesion and de-adhesion. Cathepsin X, a cysteine protease, has been
      shown to regulate T-cell migration by interaction with lymphocyte function
      associated antigen-1 (LFA-1). LFA-1 adhesion to the ICAM-1 is controlled by the
      association of actin-binding proteins with the cytoplasmic tail of the beta(2)
      chain of LFA-1. Cleavage by cathepsin X of the amino acid residues S(769), E(768)
      and A(767) from the C-terminal of the beta(2) cytoplasmic tail of LFA-1 is shown
      to promote binding of the actin-binding protein alpha-actinin-1. Furthermore,
      cathepsin X overexpression reduced LFA-1 clustering and induced an intermediate
      affinity LFA-1 conformation that is known to associate with alpha-actinin-1.
      Increased levels of intermediate affinity LFA-1 resulted in augmented cell
      spreading due to reduced attachment of T cells to the ICAM-1-coated surface.
      Gradual cleavage of LFA-1 by cathepsin X enables the transition between
      intermediate and high affinity LFA-1, an event that is crucial for effective T
      cell migration.

PMID- 19750480
TI  - Evidence that cathelicidin peptide LL-37 may act as a functional ligand for CXCR2
      on human neutrophils.
AB  - LL-37, derived from human cathelicidin, stimulates immune responses in
      neutrophils. Although FPR2 and P2X7 were proposed as LL-37 receptors, we have
      shown that among 21 neutrophil receptors only CXCR2 was down-regulated by LL-37.
      LL-37 functions similarly to CXCR2-specific chemokines CXCL1 and CXCL7 in terms
      of receptor down-regulation and intracellular calcium mobilization on freshly
      isolated neutrophils. Neutrophils pretreated with CXCL8, a chemokine that binds
      both CXCR1/2, completely blocked the calcium mobilization in response to LL-37,
      while LL-37 also partially inhibited (125)I-CXCL8 binding to neutrophils.
      SB225002, a selective CXCR2 antagonist, blocked LL-37-induced calcium
      mobilization and migration of neutrophils. LL-37 stimulates calcium mobilization
      in CXCR2-transfected HEK293 cells, CXCR2(+) THP-1 cells and monocytes, but not in
      CXCR1-transfected HEK293 cells. WKYMVm peptide (ligand for FPR2) does not block
      LL-37-stimulated calcium flux in either THP-1 (FPR2(-)) or monocytes
      (FPR2(high)), further confirming the specificity of LL-37 for CXCR2 and not FPR2.
      Among all ligands tested (ATP, BzATP, WKYMVm, CXCL1, and LL-37), only LL-37
      stimulated migration of monocytes (CXCR2(+) and FPR2(+)) and migration was
      inhibited by the CXCR2 inhibitor SB225002. Moreover, CXCR2 but not CXCR1 was
      internalized in LL-37-treated neutrophils. Thus, our data provide evidence that
      LL-37 may act as a functional ligand for CXCR2 on human neutrophils.

PMID- 19750482
TI  - Critical role of microglial CD40 in the maintenance of mechanical
      hypersensitivity in a murine model of neuropathic pain.
AB  - We recently demonstrated a contributing role of spinal cord infiltrating CD4+ T
      lymphocytes in the maintenance of mechanical hypersensitivity in a rodent model
      of neuropathic pain, spinal nerve L5 transection (L5Tx). It has been demonstrated
      that microglia play a role in the etiology of pain states. We hypothesized that
      infiltrating CD4+ T lymphocytes communicate with microglia via a CD40-CD154
      interaction. Here, we investigated the role of CD40 in the development of
      mechanical hypersensitivity post-L5Tx. CD40 KO mice displayed significantly
      decreased mechanical sensitivity compared with WT mice starting from day 5 post
      L5Tx. Using bone marrow chimeric mice, we further identified a pro-nociceptive
      role of CNS microglial CD40 rather than the peripheral leukocytic CD40. Flow
      cytometric analysis determined a significant increase of CD40+ microglia in the
      ipsilateral side of lumbar spinal cord post-L5Tx. Further, spinal cord
      proinflammatory cytokine (IL-1beta, IL-6, IL-12, and TNF-alpha) profiling
      demonstrated an induction of IL-6 in both WT and CD40 KO mice post-L5Tx prior to
      the increase of microglial CD40 expression, indicating a CD40-independent
      induction of IL-6 following L5Tx. These data establish a novel role of microglial
      CD40 in the maintenance of nerve injury-induced behavioral hypersensitivity, a
      behavioral sign of neuropathic pain.

PMID- 19750483
TI  - Establishment of nematode infection despite increased Th2 responses and
      immunopathology after selective depletion of Foxp3+ cells.
AB  - Here, we show that Treg limit intestinal pathology during nematode infection and
      that they control the onset and magnitude of the anti-parasitic Th Th2 response.
      Using mice expressing the diphtheria toxin receptor under the control of the
      foxp3 locus, we removed Foxp3(+) Treg during the early phase of infection with
      Heligmosomoides polygyrus bakeri. Depletion of Treg in infected animals did not
      affect adult worm burden, but led to increased pathology at the site of
      infection. Infected, depleted mice displayed higher frequencies of activated
      CD4(+) T cells and increased levels of the Th2 cytokines IL-4 and IL-13. The
      stronger parasite-specific Th2 response was accompanied by higher levels of IL
      10. Only a moderate change in Th1 (IFN-gamma) reactivity was detected in worm
      infected, Treg-depleted mice. Furthermore, we detected an accelerated onset of
      parasite-specific Th2 and IL-10 responses in the transient absence of Foxp3(+)
      Treg. However, adult worm burdens were not affected by the increased Th2
      reactivity in Treg-depleted mice. Hence, our data show that Treg restrict the
      onset and strength of Th2 responses during intestinal worm infection, while
      increasing primary Th2 responses does not necessarily lead to killing of larvae
      or accelerated expulsion of adult worms.

PMID- 19750484
TI  - Membrane protein GARP is a receptor for latent TGF-beta on the surface of
      activated human Treg.
AB  - Human Treg and Th clones secrete the latent form of TGF-beta, in which the mature
      TGF-beta protein is bound to the latency-associated peptide (LAP), and is thereby
      prevented from binding to the TGF-beta receptor. We previously showed that upon
      TCR stimulation, human Treg clones but not Th clones produce active TGF-beta and
      bear LAP on their surface. Here, we show that latent TGF-beta, i.e. both LAP and
      mature TGF-beta, binds to glycoprotein A repetitions predominant (GARP), a
      transmembrane protein containing leucine rich repeats, which is present on the
      surface of stimulated Treg clones but not on Th clones. Membrane localization of
      latent TGF-beta mediated by binding to GARP may be necessary for the ability of
      Treg to activate TGF-beta upon TCR stimulation. However, it is not sufficient as
      lentiviral-mediated expression of GARP in human Th cells induces binding of
      latent TGF-beta to the cell surface, but does not result in the production of
      active TGF-beta upon stimulation of these Th cells.

PMID- 19750485
TI  - Zinc-finger intron 7: a new locus for sex identification of giant panda
      (Ailuropoda melanoleuca).
AB  - We developed a single-reaction test for identifying the sex of giant panda
      (Ailuropoda melanoleuca) targeted to co-amplify homologous fragments with size
      polymorphism that located at zinc-finger (ZF) intron 7 by using one pair of
      primers. This assay produced one sex-specific fragment in females (XX genotypes)
      whereas two fragments were produced in males (XY genotypes). Indels
      (insertion/deletion) in intron 7 of Y-linked allele provide a significant
      discrimination between ZFX and ZFY, thus the amplification products can be simply
      distinguished by agarose gel electrophoresis, exhibiting sex-specific banding
      patterns (female, 354 bp; male, 354 bp, 135 bp). The new primer set was
      successfully tested on known-sex giant pandas by using template DNA extracted
      from both blood and fecal samples. Cross-species test was also performed,
      revealing that this assay could be applied to other Ursidae species.

PMID- 19750486
TI  - Expression pattern of two collagen type 2 alpha1 genes in the Japanese inshore
      hagfish (Eptatretus burgeri) with special reference to the evolution of
      cartilaginous tissue.
AB  - Collagen type 2 alpha1 (Col2A1) protein is a major component of the cartilaginous
      extracellular matrix (ECM) in vertebrates. Over the past two decades, the
      evolutionary origin of Col2A1 has been studied at the biochemical and molecular
      levels in extant jawless vertebrates (hagfishes and lampreys). Although these
      studies have contributed to our understanding of ECM protein evolution, the
      expression profile of the Col2A1 gene in hagfishes has not been fully described.
      We have performed molecular cloning and analyzed the gene expression pattern of
      the Col2A1 gene in the Japanese inshore hagfish (Eptatretus burgeri). We
      succeeded in isolating two Col2A1 genes, EbCol2A1A and EbCol2A1B, in which
      EbCol2A1A was expressed in the noncartilaginous connective tissues whereas
      EbCol2A1B was detected in some cartilaginous elements. Based on these results, we
      discuss the evolutionary history of Col2A1 genes in early vertebrates.

PMID- 19750487
TI  - Gestational high saturated fat diet alters C57BL/6 mouse perinatal skeletal
      formation.
AB  - BACKGROUND: Our present work joins growing evidence that gestational environment
      (maternal nutrition, health, and chemical exposures) strongly influences prenatal
      development (www.thebarkertheory.org). The present study suggests that maternal
      consumption of a diet high in saturated fats (HFD), which approximates the
      macronutrient content of fast food, impairs perinatal skeletal development.
      METHODS: In this study, administration of HFD (32% saturated fat) for one month
      prior to conception and throughout gestation in C57BL/6J mice was associated with
      a marked reduction in late-gestation fetal skeletal developmental delay that
      included shorter long bone lengths, decreased average bone mineral density (ABMD;
      20%), lower total bone volume (TBV; 45%), and shorter crown-to-rump length (C-R;
      12%), as compared to controls. RESULTS: A putative mechanism linking prenatal HFD
      to dysregulated fetal osteogenesis is HFD-induced oxidative stress (OS), which
      has been shown in our laboratory to cause placental labyrinthine vascular damage
      and impaired fetal signaling pathways associated with osteogenesis (Liang et al.,
      unpublished data). CONCLUSIONS: The theory of HFD-associated, OS-mediated
      placental damage and skeletal pathogenesis was supported by demonstrating a
      protective effect of the dietary antioxidant quercetin (Q) against HFD-associated
      fetal skeletal developmental delay. Improved understanding of the role of HFD and
      elevated OS in fetal skeletal development will help to more completely elucidate
      the importance of the prenatal environment to fetal formation, and will be
      applied to better understand the contribution of the fetal environment to long
      term risk of adult-onset disease.

PMID- 19750488
TI  - Intrauterine exposure to high saturated fat diet elevates risk of adult-onset
      chronic diseases in C57BL/6 mice.
AB  - BACKGROUND: The developmental environment is thought to determine, in part,
      lifelong metabolic parameters and risk of adult disease. Effects of maternal
      malnutrition on fetal growth have been studied extensively, and the role of poor
      prenatal diet in elevating lifelong risk of cardiovascular and metabolic disease
      has been well characterized (www.thebarkertheory.com). However, the contribution
      of gestational high saturated fat diet (HFD) to adult-onset metabolic disease and
      skeletal dysfunction has only recently been recognized, and as such is
      incompletely understood. METHODS: The present study evaluates the
      pathophysiologic mechanisms linking gestational HFD (approximating the
      macronutrient content of fast food) and elevated oxidative stress (OS) to adult
      onset skeletal, cardiovascular, and metabolic dysfunction. RESULTS: Results of
      this study demonstrate that adult offspring of dams fed HFD during pregnancy
      exhibited adult hyperglycemia, insulin resistance, obesity, and hypertension,
      despite being fed healthy standard rodent chow throughout postnatal life. These
      offspring also showed significantly lower femoral epiphyseal average bone mineral
      density (ABMD) at 6 months of age, and dysregulation of distal femoral trabecular
      architecture at 12 months of age, characteristic of osteoporosis. Incidence of
      these adult-onset adverse skeletal and metabolic effects was reduced by
      supplementing the pregnant dam with the antioxidant (quercetin, Q) during
      pregnancy. CONCLUSIONS: Collectively, these data suggest that offspring of dams
      who consume a diet rich in saturated fats during pregnancy are at increased risk
      of adult-onset chronic disease. Additionally, these chronic diseases were
      determined to be in-part OS-mediated, and preventable by increasing a prenatal
      dietary antioxidant; this knowledge offers both a putative mechanism of disease
      pathogenesis and suggests a potential preventive strategy.

PMID- 19750489
TI  - Quality specifications for peptide drugs: a regulatory-pharmaceutical approach.
AB  - Peptide drugs, as all types of pharmaceuticals, require adequate specifications
      (i.e. quality attributes, procedures and acceptance criteria) as part of their
      quality assurance to ensure the safety and efficacy of drug substances (i.e.
      active pharmaceutical ingredients) and drug products (i.e. finished
      pharmaceutical dosage forms). Compendial monographs are updated regularly to keep
      up with the most recent advances in peptide synthesis (e.g. reduced by-products)
      and analytical technology. Nevertheless, currently applied pharmacopoeial peptide
      specifications are barely harmonized yet (e.g. large differences between the
      European Pharmacopoeia and the United States Pharmacopeia), increasing the
      manufacturers' burden of performing analytical procedures in different ways,
      using different acceptance criteria. Additionally, the peptide monographs are not
      always consistent within a single pharmacopoeia. In this review, we highlight the
      main differences and similarities in compendial peptide specifications (including
      identification, purity and assay). Based on comparison, and together with
      additional information from peptide drug substance manufacturers and public
      evaluation reports on registration files of non-pharmacopoeial peptide drugs, a
      consistent monograph structure is proposed.

PMID- 19750490
TI  - VISIONS: the art of science: attachment between muscles and tendons.

PMID- 19750493
TI  - Essential tremor--neurodegenerative or nondegenerative disease towards a working
      definition of ET.
AB  - Essential tremor (ET) is a syndrome of tremor in posture and movement, but recent
      studies have revealed additional cerebellar motor disturbances, cognitive
      disturbances, personality changes, hearing loss, and olfactory deficits. Even
      dementia and shortened life expectancy were found in one cohort. Recent
      postmortem studies have found limited Lewy body pathology in some patients and
      Purkinje cell loss with torpedoes and Bergmann gliosis in others. These findings
      have led to the hypothesis that ET is a syndrome produced by at least two
      neurodegenerative diseases with more widespread clinical consequences than
      previously appreciated. We review the evidence for and against this hypothesis
      and conclude that studies purporting to support this hypothesis have failed to
      control for age-associated comorbidities, depression, medications, and other
      confounding factors. We propose the alternative hypothesis that abnormal neuronal
      oscillation is the fundamental abnormality in ET, and the well-documented
      cerebellar signs and symptoms, the controversial non-motor signs, and even the
      cerebellar pathology of ET could be caused by this oscillation. A major problem
      for many studies is the lack of a diagnostic gold standard. Lacking such a
      standard, we propose a subclassification of ET into three categories: hereditary
      ET, sporadic ET, and senile ET, which we believe will help researchers resolve
      many of the controversies in this field.

PMID- 19750494
TI  - Deep brain stimulation in acute management of status dystonicus.

PMID- 19750495
TI  - Circular dichroism spectra, optical rotations and absolute configurations of cis
      dihydrodiol metabolites of quinoline and derivatives: the role of the nitrogen
      atom.
AB  - The absolute configurations of cis-dihydrodiol bacterial metabolites derived from
      quinoline substrates and their quinolinium salts have been determined by
      comparison of experimental and calculated chiroptical data (circular dichroism
      spectra and optical rotations). The role of intramolecular H-bonding and other
      interactions in the preferred conformations has been investigated, including the
      effect of protonation of several cis-dihydrodiols. The presence of a strong
      intramolecular OH...N bond in several cis-dihydrodiol metabolites suggests that
      such species have a residually chiral oxygen atom.

PMID- 19750496
TI  - Fipronil resistance in the whitebacked planthopper (Sogatella furcifera):
      possible resistance mechanisms and cross-resistance.
AB  - BACKGROUND: The whitebacked planthopper (WBPH), Sogatella furcifera (Horvath), is
      a major rice pest in many parts of Asia. Fipronil has been widely used to control
      rice pests, and resistance to fipronil has been reported in some important
      species. RESULTS: A field population (F) of WBPH was collected, with 50.5-fold
      resistance to fipronil, which increased to 137.5-fold (F-se) after continuous
      selection for 11 generations. The F-se population did not show significant cross
      resistance to the insecticides examined by comparison with the F population. TPP
      (synergism ratio 1.9), DEM (1.5) and PBO (1.1) showed only slight synergism on
      fipronil in the F-se population. A large increase was found in esterase and P450
      monooxygenase activity in the F-se population. In vitro, PBO inhibited both
      esterase and P450 monooxygenase activity, and TPP inhibited esterase activity in
      the F-se population. CONCLUSION: Synergistic study in vivo and biochemical study
      in vitro indicated that esterase and P450 monooxygenases might be important
      factors for fipronil resistance in the selected population F-se. However, these
      biochemical factors could not lead to such high resistance (137.5-fold) in the F
      se population, and target-site insensitivity would be another or more important
      factor.

PMID- 19750497
TI  - Characterization of folded conformations in a tetrapeptide containing two
      tryptophan residues by vibrational circular dichroism.
AB  - The intramolecularly hydrogen bonded conformations of the tetrapeptide Boc-Trp
      Aib-Gly-Trp-OMe (WUGW) are investigated using experimental and quantum chemical
      predictions of vibrational circular dichroism (VCD) in the 1800-1550 cm(-1)
      region. The predicted VCD spectrum, for a conformation (conformer A) obtained
      from optimization of crystal structure, reproduced the dominant negative VCD band
      observed experimentally in CH(3)OH and CHCl(3) solvents. However, the predicted
      VCD spectrum of Conformation A also has an extra positive band which is not seen
      in the experimental spectra. This mismatch appears to be due to the lack of
      solvent influence in the quantum chemical geometry optimizations. However,
      Conformations I and II, obtained, respectively, from constrained optimization of
      crystal and NMR structures, mimic the solvent stabilized structures and are
      predicted to have dominant negative VCD band as found in the experimental
      spectra. It is noted that, for the peptide investigated here, unconstrained
      quantum chemical geometry optimizations in vacuum converged to structures that
      are not the realistic models of conformations found in solution. It is also noted
      that undertaking quantum chemical vibrational property calculations directly
      using geometries obtained from crystal data or NMR data resulted in unrealistic
      vibrational frequencies and descriptions. However, constraining the backbone
      dihedral angles to those found in condensed medium, and optimizing the remaining
      geometrical parameters resulted in a better reproduction of the observed VCD in
      condensed medium. The vibrational origins of bands in all of the predicted VCD
      spectra for the WUGW-tetrapeptide have also been presented.

PMID- 19750498
TI  - Theoretical approaches to the calculation of Raman optical activity spectra.
AB  - In this article, we will give a brief account of the different approaches that
      have been presented in the literature for calculating Raman optical activity
      (ROA) spectra by ab initio methods. We will also outline the general structure of
      a self-consistent-field-based approach for analytic calculations of ROA spectra,
      including also contributions from London orbitals. The use of London orbitals
      ensures that the relevant ROA parameters are gauge origin independent. We will
      also give an outlook on the future of ab initio calculations of Raman optical
      activity spectra.

PMID- 19750499
TI  - Effect of temperature on the enantioselectivity of basic analytes using CE with
      sulfated beta-cyclodextrins.
AB  - Twelve basic analytes, including ephedrine and its structurally related
      compounds, were used to study the influence of capillary temperature on
      enantioselectivity in CE enantioseparations under reversed polarity mode using
      sulfated beta-CD (S-beta-CD) as chiral selectors. All of the effective mobility
      changes of (+)-enantiomers between 35 and 20 degrees C were higher than those of
      (-)-enantiomers whosoever enantioselectivity increased or decreased with an
      increase in temperature. However, the unusual temperature effect that
      enantioselectivity was increased with an increase of temperature was observed for
      the compounds with hydroxyl substitution on phenyl ring and had relationship with
      the molecular structures. With performing NMR studies on the selected selector
      analyte complexes, the results led to a deeper understanding of the chiral
      discrimination process. Inspection of the complexation-induced chemical shifts
      (CICS) of the enantiomers showed that the phenyl ring sits deeply and slantways
      in the cavity of S-beta-CD and alkyl chain pointed out of the wider rim of S-beta
      CD with ion-ion and hydrogen bond interactions between analytes and S-beta-CD.

PMID- 19750500
TI  - Comparative analysis of volatile constituents in Citrus reticulata Blanco using
      GC-MS and alternative moving window factor analysis.
AB  - The similarities and differences of essential oil components in Album Citri
      reticulatae (ACR), Cylindricae Citri reticulatae (CCR), folium Citri reticulatae
      (FCR), exocarpium Citri Grandis (ECG), pericarpium Citri reticulatae Viride
      (PCRV) and pericarpium Citri reticulatae (PCR) were investigated by GC-MS
      combined with a chemometric method named alternative moving window factor
      analysis (AMWFA). And temperature-programmed retention indices (PTRIs) were used
      together with mass spectra for identification of the essential oil components. In
      essential oils of ACR, CCR, FCR, ECG, PCRV and PCR, 28, 26, 61, 62, 52 and 48
      components were determined representing 93.13, 94.44, 93.53, 87.67, 99.03 and
      98.03% of the total relative content, respectively. Also, the essential oils
      significantly differed both qualitatively and quantitatively. There were 14
      common components among ACR, CCR, FCR, ECG, PCRV and PCR, their abundance varied
      in the ranges from 32.39% in FCR to 94.66% in PCRV. The results obtained may be
      helpful to the further study of pharmacological activity for their potential
      utilization as therapeutical agents.

PMID- 19750501
TI  - Rapid determination of losartan and losartan acid in human plasma by multiplexed
      LC-MS/MS.
AB  - A rapid LC-MS/MS method has been developed and validated for the determination of
      losartan (LOS) and its metabolite losartan acid (LA) (EXP-3174) in human plasma
      using multiplexing technique (two HPLC units connected to one MS/MS). LOS and LA
      were extracted from human plasma by SPE technique using Oasis HLB cartridge
      without evaporation and reconstitution steps. Hydroflumethiazide (HFTZ) was used
      as an internal standard (IS). The analytes were separated on Zorbax SB C-18
      column. The mass transition [M-H] ions used for detection were m/z 421.0 -->
      127.0 for LOS, m/z 435.0 --> 157.0 for LA, and m/z 330.0 --> 239.0 for HFTZ. The
      proposed method was validated over the concentration range of 2.5-2000 ng/mL for
      LOS and 5.0-3000 ng/mL for LA with correlation coefficient > or = 0.9993. The
      overall recoveries for LOS, LA, and IS were 96.53, 99.86, and 94.16%,
      respectively. Total MS run time was 2.0 min/sample. The validated method has been
      successfully used to analyze human plasma samples for applications in 100 mg
      fasted and fed pharmacokinetic studies.

PMID- 19750502
TI  - Simultaneous enrichment and separation of neutral and anionic analytes through
      combining large volume sample stacking with sweeping in CE.
AB  - In this work, we overcame the deficiencies of large volume sample stacking (LVSS)
      in separating low-mobility and neutral analytes through combining LVSS with
      sweeping in CE, and employed this new approach to enrich and separate neutral and
      anionic analytes simultaneously. This technique was carried out with pressure
      injection of large-volume sample followed by EOF as a pump pushing the bulk of
      low-conductivity sample matrix out of the outlet of the capillary while analytes
      were swept by micelles and separated via MEKC without the electrode polarity
      switching. Careful optimization of the enrichment and separation conditions
      allowed the enrichment factors (EFs) of peak height and peak area of the analytes
      to be in the range of 9-33 and 21-35 comparing with the conventional injection
      mode, respectively. The five analytes were baseline separated in 15 min and the
      detection limits ranged from 26.5 to 55.8 ng/mL (S/N = 3). The developed method
      was successfully applied to determine adenine, caffeine, theophylline, reduced L
      glutathione (GSH) and oxidized L-glutathione (GSSG) in two different teas with
      recoveries that ranged from 84.4 to 105.2%.

PMID- 19750503
TI  - Direct characterization of aqueous extract of Hibiscus sabdariffa using HPLC with
      diode array detection coupled to ESI and ion trap MS.
AB  - The phenolic fraction and other polar compounds of the Hibiscus sabdariffa were
      separated and identified by HPLC with diode array detection coupled to
      electrospray TOF and IT tandem MS (DAD-HPLC-ESI-TOF-MS and IT-MS). The H.
      sabdariffa aqueous extract was filtered and directly injected into the LC system.
      The analysis of the compounds was carried out by RP HPLC coupled to DAD and TOF
      MS in order to obtain molecular formula and exact mass. Posterior analyses with
      IT-MS were performed and the fragmentation pattern and confirmation of the
      structures were achieved. The H. sabdariffa samples were successfully analyzed in
      positive and negative ionization modes with two optimized linear gradients. In
      positive mode, the two most representative anthocyanins and other compounds were
      identified whereas the phenolic fraction, hydroxycitric acid and its lactone were
      identified using the negative ionization mode.

PMID- 19750504
TI  - Capillary electrophoresis using core-based hyperbranched polyethyleneimine
      (CHPEI) static-coated capillaries.
AB  - With unique 3-D architecture, the application of core-based hyperbranched
      polyethyleneimine (CHPEI), as a capillary coating in capillary electrophoresis,
      is demonstrated by manipulation of the electroosmotic mobility (EOF). CHPEI
      coatings (CHPEI5, M(w) approximately 5000 and CHPEI25, M(w) approximately 25,000)
      were physically adsorbed onto the inner surface of bare fused-silica capillary
      (BFS) via electrostatic interaction of the oppositely charged molecules by
      rinsing the capillaries with different CHPEI aqueous solutions. The EOF values of
      the coated capillaries were measured over the pH range of 4.0-9.0. At higher pH
      (pH >6) the coated capillary surface possesses excess negative charges, which
      causes the reversal of the EOF. The magnitudes of the EOF obtained from the
      coated capillaries were three-fold lower than that of BFS capillary. Desirable
      reproducibility of the EOF with % RSD (n = 5) < or = 2 was obtained. Effect of
      ionic strength, stability of the coating (% RSD = 0.3) and the dependence of the
      EOF on pH (% RSD = 0.5) were also investigated. The CHPEI-coated capillaries were
      successfully utilized to separate phenolic compounds, B vitamins, as well as
      basic drugs and related compounds with reasonable analysis time (< 20 min) and
      acceptable migration-time repeatability (< 0.7% RSD for intra-capillary and < 2%
      RSD for inter-capillary).

PMID- 19750505
TI  - Ultrafast UPLC-ESI-MS and HPLC with monolithic column for determination of
      principal flavor compounds in vanilla pods.
AB  - In this study, two novel chromatographic methods based on monolithic column high
      performance liquid chromatography (HPLC) and ultra-performance liquid
      chromatography (UPLC) were developed for the ultrafast determination of principal
      flavor compounds namely vanillin, vanillic acid, p-hydroxybenzoic acid, and p
      hydroxybenzaldehyde in ethanolic extracts of Vanilla planifolia pods. Good
      separation was achieved within 2.5 min using Chromolith RP18e column (100 mm x
      4.6 mm) for HPLC and Acquity BEH C-18 (100 mm x 2.1 mm, 1.7 microm) column for
      UPLC. Both methods were compared in terms of total analysis time, mobile phase
      consumption, sensitivity, and validation parameters like precision, accuracy,
      LOD, and LOQ. Further, system suitability test data including resolution,
      capacity factor, theoretical plates, and tailing factor was determined for both
      the methods by ten replicate injections. Monolithic column based HPLC gave better
      results for most of the selected parameters while UPLC was found to be more eco
      friendly with low mobile phase consumption and better sensitivity. Both methods
      may be used conveniently for the high throughput analysis of large number of
      samples in comparison to traditional particulate column.

PMID- 19750506
TI  - Prediction of immobilized artificial membrane-liquid chromatography retention of
      some drugs from their molecular structure descriptors and LFER parameters.
AB  - In this work multiple linear regression (MLR) was carried out for the prediction
      of immobilized artificial membrane (IAM) retention factors of 40 basic and
      neutral drugs in two mobile phase compositions. We developed some MLR models by
      using linear free energy relationships (LFER) parameters and also theoretically
      derived molecular descriptor. Root mean square error of MLR model in prediction
      of log k(wPBS)(IAM) and k(wMOPS)(IAM) are 0.332 and 0.351, respectively, while
      these values are 0.371 and 0.500 for LFER models. Inspections to these values
      indicate that the statistical parameters of MLR models are better than LFER
      models. The credibility of MLR models was evaluated by using leave-many-out cross
      validation and y-scrambling procedures. The results of these tests indicate the
      applicability of theoretically derived molecular descriptors and LFER parameters
      prediction of IAM retention of drugs.

PMID- 19750507
TI  - Comparison of the volatile constituents of different parts of Cortex magnolia
      officinalis by GC-MS combined with chemometric resolution method.
AB  - Volatile compositions of different parts (stem, branch and root barks) of cortex
      Magnolia officinalis, cultivated in China, were investigated for the first time
      by GC-MS with the help of heuristic evolving latent projection (HELP).
      Identification of components was conducted by similarity matching to NIST mass
      library but also assisted by comparison of temperature-programmed retention
      indices (PTRIs) with the data web available. A total of 90, 82 and 76 volatile
      compounds in the essential oils of the three samples taken from the same batch
      aforementioned were qualitatively and quantitatively determined, representing
      84.03, 83.68 and 83.10% of the total content, respectively. Among the
      constituents determined, there were 50 components coexisting. Eudesmol and its
      isomers were shown to be the principal compounds in the studied samples,
      accounting for 47.66, 36.74 and 36.31%, respectively. The three kinds of isomers
      (alpha-, beta- and gamma-eudesmol) in houpo volatile oils have been tentatively
      qualified and quantified simultaneously for the first time. By comparative
      analysis, significant qualitative and semi-quantitative differences and
      similarities were observed among the three samples. The results achieved provide
      a scientific evidence for further exploitation of Magnolia bark and clinical
      medication.

PMID- 19750508
TI  - Fast and simple method for the determination of urinary 1-hydroxypyrene.
AB  - A fast method for the measurement of metabolites of pyrene in urine was improved
      by HPLC with fluorescence detector using "heart-cut" technique. This method can
      quantify the total amount of pyrene metabolites corresponding to glucuronic acid
      and sulfate conjugates as well as free 1-OH-Py. The hydrolyzed biological fluid
      was directly injected into the chromatographic system, via a column-switching
      system. Pre-treatment and analysis were performed within 0.5 and 9 min,
      respectively. Enzymatic hydrolysis has been optimized to not exceed 2 h. The best
      response function, in the 0.2-10 ng/mL range, is the linear regression, bringing
      simplicity, good accuracy, and low LOQ. The intra- and interday precision values
      were inferior to 1 and 2%, respectively. The proposed method provided a simple,
      convenient, and practical procedure to determine the level of the main urinary
      pyrene metabolites in biological samples.

PMID- 19750509
TI  - Analysis of polycyclic aromatic hydrocarbons in fish: evaluation of a quick,
      easy, cheap, effective, rugged, and safe extraction method.
AB  - QuEChERS method was evaluated for extraction of 16 PAHs from fish samples. For a
      selective measurement of the compounds, extracts were analysed by LC with
      fluorescence detection. The overall analytical procedure was validated by
      systematic recovery experiments at three levels and by using the standard
      reference material SRM 2977 (mussel tissue). The targeted contaminants, except
      naphthalene and acenaphthene, were successfully extracted from SRM 2977 with
      recoveries ranging from 63.5-110.0% with variation coefficients not exceeding 8%.
      The optimum QuEChERS conditions were the following: 5 g of homogenised fish
      sample, 10 mL of ACN, agitation performed by vortex during 3 min. Quantification
      limits ranging from 0.12-1.90 ng/g wet weight (0.30-4.70 microg/L) were obtained.
      The optimized methodology was applied to assess the safety concerning PAHs
      contents of horse mackerel (Trachurus trachurus), chub mackerel (Scomber
      japonicus), sardine (Sardina pilchardus) and farmed seabass (Dicentrarchus
      labrax). Although benzo(a)pyrene, the marker used for evaluating the carcinogenic
      risk of PAHs in food, was not detected in the analysed samples (89 individuals
      corresponding to 27 homogenized samples), the overall mean concentration ranged
      from 2.52 +/- 1.20 ng/g in horse mackerel to 14.6 +/- 2.8 ng/g in farmed seabass.
      Significant differences were found between the mean PAHs concentrations of the
      four groups.

PMID- 19750510
TI  - Reinforcement learning design for cancer clinical trials.
AB  - We develop reinforcement learning trials for discovering individualized treatment
      regimens for life-threatening diseases such as cancer. A temporal-difference
      learning method called Q-learning is utilized that involves learning an optimal
      policy from a single training set of finite longitudinal patient trajectories.
      Approximating the Q-function with time-indexed parameters can be achieved by
      using support vector regression or extremely randomized trees. Within this
      framework, we demonstrate that the procedure can extract optimal strategies
      directly from clinical data without relying on the identification of any accurate
      mathematical models, unlike approaches based on adaptive design. We show that
      reinforcement learning has tremendous potential in clinical research because it
      can select actions that improve outcomes by taking into account delayed effects
      even when the relationship between actions and outcomes is not fully known. To
      support our claims, the methodology's practical utility is illustrated in a
      simulation analysis. In the immediate future, we will apply this general strategy
      to studying and identifying new treatments for advanced metastatic stage IIIB/IV
      non-small cell lung cancer, which usually includes multiple lines of chemotherapy
      treatment. Moreover, there is significant potential of the proposed methodology
      for developing personalized treatment strategies in other cancers, in cystic
      fibrosis, and in other life-threatening diseases.

PMID- 19750511
TI  - An improved strategy for tandem affinity purification-tagging of
      Schizosaccharomyces pombe genes.
AB  - Tandem affinity purification (TAP) is a method that allows rapid purification of
      native protein complexes. We developed an improved technique to fuse the fission
      yeast genes with a TAP tag. Our technique is based on tagging constructs that
      contain regions homologous to the target gene cloned into vectors carrying a TAP
      tag. We used this technique to design strategies for TAP-tagging of predicted
      Schizosaccharomyces pombe genes (http://mendel.imp.ac.at/Pombe_tagging/). To
      validate the approach, we purified the proteins, which associated with two
      evolutionarily conserved proteins Swi5 and Sfr1 as well as three protein kinases
      Ksg1, Orb6 and Sid1.

PMID- 19750512
TI  - A three-way proteomics strategy allows differential analysis of yeast
      mitochondrial membrane protein complexes under anaerobic and aerobic conditions.
AB  - To investigate the effect of anaerobiosis on the Saccharomyces cerevisiae
      mitochondrial proteome and the formation of respiratory chain and other protein
      complexes, we analyzed mitochondrial protein extracts that were enriched from
      lysates of aerobic and anaerobic steady-state chemostat cultures. We chose an
      innovative approach in which native mitochondrial membrane protein complexes were
      separated by 1-D blue native PAGE, which was combined with quantitative analysis
      of each complex subunit using stable isotope labeling. LC-FT(ICR)-MS/MS analysis
      was applied to identify and quantify the mitochondrial proteins. In addition, to
      establish if changes in mitochondrial complex composition occurred under
      anaerobiosis, we investigated the 1-D blue native PAGE protein migration patterns
      by Pearson correlation analysis. Surprisingly, we discovered that under anaerobic
      conditions, where the yeast respiratory chain is not active, the respiratory
      chain supercomplexes, such as complex V dimer, complex (III)(2)(IV)(2) and
      complex (III)(2)(IV) were still present, although at reduced levels. Pearson
      correlation analysis showed that the composition of the mitochondrial complexes
      was unchanged under aerobic or anaerobic conditions, with the exception of
      complex II. In addition, this latter approach allowed screening for possible
      novel complex interaction partners, since for example protein Aim38p, with a yet
      unknown function, was identified as a possible component of respiratory chain
      complex IV.

PMID- 19750513
TI  - Development of a new method for absolute protein quantification on 2-D gels.
AB  - With the development of systems biology projects aimed at modeling the cell,
      accurate and absolute measurements of cellular protein concentrations are
      increasingly important. However, methods for absolute quantification at the
      proteomic level remain rare. Using the yeast Saccharomyces cerevisiae, we propose
      a new method based on the radioactive labeling with an (35)S compound and 2-D
      PAGE. The principle is simple: cells are grown for more than four generations in
      the presence of a unique sulfur source labeled at a defined specific
      radioactivity, ensuring that more than 90% of the proteins are labeled at the
      same specific radioactivity as the sulfur source. After separation of (35)S
      labeled proteins on 2-D gels, each protein is counted. The amount of each protein
      present in the gel is then calculated, from which is deduced the amount of each
      protein per cell. The method, limited to soluble and abundant proteins visible on
      2-D gels, is simple, precise and reproducible and does not require an internal
      standard. We use it to compare the amounts of proteins in two growth conditions:
      100 microM sulfate or 500 microM methionine. Up to now, we only had
      transcriptional data on the expression of these proteins in both conditions.

PMID- 19750514
TI  - MALDI-TOF MS-based drug susceptibility testing of pathogens: the example of
      Candida albicans and fluconazole.
AB  - MALDI-TOF MS can be used for the identification of microorganism species. We have
      extended its application to a novel assay of Candida albicans susceptibility to
      fluconazole, based on monitoring modifications of the proteome of yeast cells
      grown in the presence of varying drug concentrations. The method was accurate,
      and reliable, and showed full agreement with the Clinical Laboratory Standards
      Institute's reference method. This proof-of-concept demonstration highlights the
      potential for this approach to test other pathogens.

PMID- 19750515
TI  - Upc2p-associated differential protein expression in Candida albicans.
AB  - The gain-of-function mutation G648D in UPC2 causes ERG11 up-regulation and
      increased fluconazole resistance in Candida albicans. In this study, we performed
      2-DE and PMF to identify proteomic alterations in an ERG11-overexpressing
      fluconazole-resistant C. albicans clinical isolate compared with its fluconazole
      susceptible parent strain. We identified 23 differentially expressed proteins,
      and among them, seven became differentially expressed in a C. albicans wild-type
      strain after the introduction of a UPC2 allele carrying this mutation. These
      Upc2p-regulated proteins may contribute to fluconazole resistance in C. albicans.

PMID- 19750516
TI  - Lymphatic development.
AB  - The lymphatic system is essential for fluid homeostasis, immune responses, and
      fat absorption, and is involved in many pathological processes, including tumor
      metastasis and lymphedema. Despite its importance, progress in understanding the
      origins and early development of this system has been hampered by lack of
      defining molecular markers and difficulties in observing lymphatic cells in vivo
      and performing genetic and experimental manipulation of the lymphatic system.
      Recent identification of new molecular markers, new genes with important
      functional roles in lymphatic development, and new experimental models for
      studying lymphangiogenesis has begun to yield important insights into the
      emergence and assembly of this important tissue. This review focuses on the
      mechanisms regulating development of the lymphatic vasculature during
      embryogenesis.

PMID- 19750518
TI  - Epidermal patterning and induction of different hair types during mouse embryonic
      development.
AB  - An intriguing question in developmental biology is how epidermal pattern
      formation processes are established and what are the molecular mechanisms
      involved in these events. The establishment of the pattern is concomitant with
      the formation of ectodermal appendages, which involves complex interactions
      between the epithelium and the underlying mesenchyme. Among ectodermal
      appendages, hair follicles are the "mini organs" that produce hair shafts.
      Several developmental and structural features are common to all hair follicles
      and to the hair shaft they produce. However, many different hair types are
      produced in a single organism. Also, different characteristics can be observed
      depending on the part of the body where the hair follicle is formed. Here, we
      review the mechanisms involved in the patterning of different hair types during
      mouse embryonic development as well as the influence of the body axes on hair
      patterning.

PMID- 19750519
TI  - Saving hearts through basic research.
AB  - Despite the recent advances in molecular medicine and health care, cardiovascular
      diseases are still the leading cause of morbidity and mortality throughout the
      world. In 2006, nearly every other death in Germany resulted from disease of the
      circulatory system, and congenital heart diseases are thought to account for a
      high number of stillbirths and spontaneous abortions. Remarkable progress in
      basic research over the past decades has improved our understanding of the
      molecular mechanisms that govern a cardiac fate and has helped to establish cell
      based therapeutic approaches to improve the course of cardiovascular diseases.

PMID- 19750517
TI  - Pancreas cell fate.
AB  - Diabetes is characterized by decreased function of insulin-producing beta cells
      and insufficient insulin output resulting from an absolute (Type 1) or relative
      (Type 2) inadequate functional beta cell mass. Both forms of the disease would
      greatly benefit from treatment strategies that could enhance beta cell
      regeneration and/or function. Successful and reliable methods of generating beta
      cells or whole islets from progenitor cells in vivo or in vitro could lead to
      restoration of beta cell mass in individuals with Type 1 diabetes and enhanced
      beta cell compensation in Type 2 patients. A thorough understanding of the normal
      developmental processes that occur during pancreatic organogenesis, for example,
      transcription factors, cell signaling molecules, and cell-cell interactions that
      regulate endocrine differentiation from the embryonic pancreatic epithelium, is
      required in order to successfully reach these goals. This review summarizes our
      current understanding of pancreas development, with particular emphasis on
      factors intrinsic or extrinsic to the pancreatic epithelium that are involved in
      regulating the development and differentiation of the various pancreatic cell
      types. We also discuss the recent progress in generating insulin-producing cells
      from progenitor sources.

PMID- 19750520
TI  - Specification of cell fate in the mammalian cochlea.
AB  - Mammalian auditory sensation is mediated by the organ of Corti, a specialized
      sensory epithelium found in the cochlea of the inner ear. Proper auditory
      function requires that the many different cell types found in the sensory
      epithelium be precisely ordered within an exquisitely patterned cellular mosaic.
      The development of this mosaic depends on a series of cell fate decisions that
      transform the initially nearly uniform cochlear epithelium into the complex
      structure of the mature organ of Corti. The prosensory domain, which contains the
      progenitors of both the mechanosensory hair cells and their associated supporting
      cells, first becomes distinct from both the neural and the nonsensory domains.
      Further cell fate decisions subdivide prosensory cells into populations of inner
      and outer hair cells, and several different types of supporting cells. A number
      of different signaling pathways and transcription factors are known to be
      necessary for these developmental processes; in this review, we will summarize
      these results with an emphasis on recent findings.

PMID- 19750521
TI  - Molecular regulation of vertebrate retina cell fate.
AB  - The specification of retinal cell fate is a multistep process that begins during
      early development and results from the spatio-temporal coordination of cell
      cycle, cell differentiation, and morphogenesis. This review focuses on recent
      advances in understanding the molecular mechanisms underlying the distinct steps
      of retinal specification. Emphasis is placed on key regulatory events that
      control the multipotency of retinal progenitors, the generation of cell
      diversity, and the establishment of the clock that determines the ordered
      generation of retinal cell types. These basic studies have paved the way to the
      latest progress on the isolation and in vitro generation of retinal stem cells,
      which is presented in the light of possible therapeutic applications.

PMID- 19750524
TI  - Cell fate determination during tooth development and regeneration.
AB  - Teeth arise from sequential and reciprocal interactions between the oral
      epithelium and the underlying cranial neural crest-derived mesenchyme. Their
      formation involves a precisely orchestrated series of molecular and morphogenetic
      events, and gives us the opportunity to discover and understand the nature of the
      signals that direct cell fates and patterning. For that reason, it is important
      to elucidate how signaling factors work together in a defined number of cells to
      generate the diverse and precise patterned structures of the mature functional
      teeth. Over the last decade, substantial research efforts have been directed
      toward elucidating the molecular mechanisms that control cell fate decisions
      during tooth development. These efforts have contributed toward the increased
      knowledge on dental stem cells, and observation of the molecular similarities
      that exist between tooth development and regeneration.

PMID- 19750525
TI  - From structure-activity to structure-selectivity relationships: quantitative
      assessment, selectivity cliffs, and key compounds.
AB  - The exploration of structure-activity relationships (SARs) in chemical lead
      optimization is mostly focused on activity against single targets. Because many
      active compounds have the potential to act against multiple targets, achieving a
      sufficient degree of target selectivity often becomes a major issue during
      optimization. Herein we report a data analysis approach to explore compound
      selectivity in a systematic and quantitative manner. Sets of compounds that are
      active against multiple targets provide a basis for exploring structure
      selectivity relationships (SSRs). Compound similarity and selectivity data are
      analyzed with the aid of network-like similarity graphs (NSGs), which organize
      molecular networks on the basis of similarity relationships and SAR index (SARI)
      values. For this purpose, the SARI framework has been adapted to quantify SSRs.
      Using sets of compounds with differential activity against four cathepsin thiol
      proteases, we show that SSRs can be quantitatively described and categorized.
      Furthermore, local SSR environments are identified, the analysis of which
      provides insight into compound selectivity determinants at the molecular level.
      These environments often contain "selectivity cliffs" formed by pairs or groups
      of similar compounds with significantly different selectivity. Moreover, key
      compounds are identified that determine characteristic features of single-target
      SARs and dual-target SSRs. The comparison of compounds involved in the formation
      of selectivity cliffs often reveals chemical modifications that render compounds
      target selective.

PMID- 19750523
TI  - Neural induction and factors that stabilize a neural fate.
AB  - The neural ectoderm of vertebrates forms when the bone morphogenetic protein
      (BMP) signaling pathway is suppressed. Herein, we review the molecules that
      directly antagonize extracellular BMP and the signaling pathways that further
      contribute to reduce BMP activity in the neural ectoderm. Downstream of neural
      induction, a large number of "neural fate stabilizing" (NFS) transcription
      factors are expressed in the presumptive neural ectoderm, developing neural tube
      and ultimately in neural stem cells. Herein, we review what is known about their
      activities during normal development to maintain a neural fate and regulate
      neural differentiation. Further elucidation of how the NFS genes interact to
      regulate neural specification and differentiation should ultimately prove useful
      for regulating the expansion and differentiation of neural stem and progenitor
      cells.

PMID- 19750526
TI  - Asymmetric transfer hydrogenation of ketones catalyzed by amino acid derived
      rhodium complexes: on the origin of enantioselectivity and enantioswitchability.
AB  - Amino acid based thioamides, hydroxamic acids, and hydrazides have been evaluated
      as ligands in the rhodium-catalyzed asymmetric transfer hydrogenation of ketones
      in 2-propanol. Catalysts containing thioamide ligands derived from L-valine were
      found to selectively generate the product with an R configuration (95 % ee),
      whereas the corresponding L-valine-based hydroxamic acids or hydrazides
      facilitated the formation of the (S)-alcohols (97 and 91 % ee, respectively). The
      catalytic reduction was examined by performing a structure-activity correlation
      investigation with differently functionalized or substituted ligands and the
      results obtained indicate that the major difference between the thioamide and
      hydroxamic acid based catalysts is the coordination mode of the ligands. Kinetic
      experiments were performed and the rate constants for the reduction reactions
      were determined by using rhodium-arene catalysts derived from amino acid
      thioamide and hydroxamic acid ligands. The data obtained show that the thioamide
      based catalyst systems demonstrate a pseudo-first-order dependence on the
      substrate, whereas pseudo-zero-order dependence was observed for the hydroxamic
      acid containing catalysts. Furthermore, the kinetic experiments revealed that the
      rate-limiting steps of the two catalytic systems differ. From the data obtained
      in the structure-activity correlation investigation and along with the kinetic
      investigation it was concluded that the enantioswitchable nature of the catalysts
      studied originates from different ligand coordination, which affects the rate
      limiting step of the catalytic reduction reaction.

PMID- 19750527
TI  - Templated synthesis of copper(II) azacyclam complexes using urea as a locking
      fragment and their metal-enhanced binding tendencies towards anions.
AB  - Copper(II) azacyclam complexes 3(2+) and 4(2+) were obtained through a metal
      templated procedure involving the pertinent open-chain tetramine, formaldehyde
      and a phenylurea derivative as a locking fragment. Both metal complexes can
      establish interactions with anions through the metal centre and the amide NH
      group. Equilibrium studies in DMSO by a spectrophotometric titration technique
      were carried out to assess the affinity of 3(2+) and 4(2+) towards anions. While
      the NH group of an amide model compound and the metal centre of the plain
      Cu(II)(azacyclam)(2+) complex do not interact at all with anions, 3(2+) and 4(2+)
      establish strong interactions with oxo anions, profiting from a pronounced
      cooperative effect. In particular, 1) they form stable 1:1 and 1:2 complexes with
      H(2)PO(4) (-) ions in a stepwise mode with both hydrogen-bonding and metal-ligand
      interactions, and 2) in the presence of CH(3)COO(-), they undergo deprotonation
      of the amido NH group and thus profit from axial coordination of the partially
      negatively charged carbonyl oxygen atom in a scorpionate binding mode.

PMID- 19750528
TI  - Atom-transfer radical addition reactions catalyzed by RuCp* complexes: a
      mechanistic study.
AB  - Kinetic and spectroscopic analyses were performed to gain information about the
      mechanism of atom-transfer radical reactions catalyzed by the complexes
      [RuCl2Cp*(PPh3)] and [RuClCp*(PPh3)2] (Cp*=pentamethylcyclopentadienyl), in the
      presence and in the absence of the reducing agent magnesium. The reactions of
      styrene with ethyl trichloroacetate, ethyl dichloroacetate, or
      dichloroacetonitrile were used as test reactions. The results show that for
      substrates with high intrinsic reactivity, such as ethyl trichloroacetate, the
      oxidation state of the catalyst in the resting state is +3, and that the reaction
      is zero-order with respect to the halogenated compound. Furthermore, the kinetic
      data suggest that the metal catalyst is not directly involved in the rate
      limiting step of the reaction.

PMID- 19750529
TI  - Anticancer agents from the Australian tropical rainforest: Spiroacetals EBC-23,
      24, 25, 72, 73, 75 and 76.
AB  - EBC-23, 24, 25, 72, 73, 75 and 76 were isolated from the fruit of Cinnamomum
      laubatii (family Lauraceae) in the Australian tropical rainforests. EBC-23 (1)
      was synthesized stereoselectively, in nine linear steps in 8 % overall yield, to
      confirm the reported relative stereochemistry and determine the absolute
      stereochemistry. Key to the total synthesis was a series of Tietze-Smith linchpin
      reactions. The novel spiroacetal structural motif, exemplified by EBC-23 (1), was
      found to inhibit the growth of the androgen-independent prostate tumor cell line
      DU145 in the mouse model, indicating potential for the treatment of refractory
      solid tumors in adults.

PMID- 19750530
TI  - Ir-Catalyzed asymmetric allylic substitutions with (phosphoramidite)Ir complexes
      resting states, synthesis, and characterization of catalytically active (pi
      allyl)Ir complexes.

PMID- 19750531
TI  - Potent fluoro-oligosaccharide probes of adhesion in Toxoplasmosis.
AB  - Unnatural, NMR- and MRI-active fluorinated sugar probes, designed and synthesised
      to bind to the pathogenic protein TgMIC1 from Toxoplasma gondii, were found to
      display binding potency equal to and above that of the natural ligand. Dissection
      of the binding mechanism and modes, including the first X-ray crystal structures
      of a fluoro-oligosaccharide bound to a lectin, demonstrate that it is possible to
      create effective fluorinated probe ligands for the study of, and perhaps
      intervention in, sugar-protein binding events.

PMID- 19750532
TI  - Biofunction-assisted sensors based on a new method for converting aptazyme
      activity into reporter protein expression with high efficiency in wheat germ
      extract.

PMID- 19750533
TI  - SERS in salt wells.
AB  - We report herein a simple, inexpensive fabrication methodology of salt
      microwells, and define the utility of the latter as nanoparticle containers for
      highly sensitive surface-enhanced Raman scattering (SERS) studies. AFM
      characterization of Ag and Au loaded salt microwells reveal the ability to
      contain favorable nanostructures such as nanoparticle dimers, which can
      significantly enhance the Raman intensity of molecules. By performing diffraction
      limited confocal Raman microscopy on salt microwells, we show high sensitivity
      and fidelity in the detection of dyes, peptides, and proteins, as a proof of our
      concept. The SERS limit of detection (accumulation time of 1 s) for rhodamine B
      and TAT contained in salt mircowells is 10 pM and 1 nM, respectively. The Raman
      characterization measurements of salt microwells with three different laser lines
      (532 nm, 632.81 nm, 785 nm) reveal low background intensity and high signal-to
      noise ratio upon nanoparticle loading, which makes them suitable for enhanced
      Raman detection. SERS mapping of these sub-femtoliter containers show spatial
      confinement of the relevant analyte to a few microns, which make them potential
      candidates for microscale bioreactors.

PMID- 19750534
TI  - Ensemble measurement of diffusion: novel beauty and evidence.
AB  - Recording the evolution of concentration profiles in nanoporous materials opens a
      new field of diffusion research with particle ensembles. The technique is based
      on the complementary application of interference microscopy and IR micro-imaging.
      Combining the virtues of diffusion measurements with solids and fluids, it
      provides information of unprecedented wealth and visual power on transport
      phenomena in molecular ensembles. These phenomena include the diverging uptake
      and release patterns for concentration-dependent diffusivities, the mechanisms of
      mass transfer at the fluid-solid interface and opposing tendencies in local and
      global concentration evolution.

PMID- 19750535
TI  - Nonviral in situ green fluorescent protein labeling and culture of primary, adult
      human hair follicle epithelial progenitor cells.
AB  - In this article we show that cloning of the human K15 promoter before a green
      fluorescence protein (GFP)/geneticin-resistance cassette and transfection of
      microdissected, organ-cultured adult human scalp hair follicles generates
      specific K15 promoter-driven GFP expression in their stem cell-rich bulge region.
      K15-GFP+ cells can be visualized in situ by GFP fluorescence and 2-photon laser
      scanning microscopy. Vital K15-GFP+ progenitor cells can then be selected by
      using the criteria of their green fluorescence, adhesion to collagen type IV and
      fibronectin, and geneticin resistance. Propagated K15-GFP+ cells express
      epithelial progenitor markers, show the expected differential gene expression
      profile of human bulge epithelium, and form holoclones. This application of
      nonretroviral, K15 promoter-driven, GFP labeling to adult human hair follicles
      facilitates the characterization and manipulation of human epithelial stem cells,
      both in situ and in vitro, and should be transferable to other complex human
      tissues.

PMID- 19750536
TI  - Mesenchymal stem cells attenuate renal fibrosis through immune modulation and
      remodeling properties in a rat remnant kidney model.
AB  - Mesenchymal stem cells (MSCs) have regenerative properties in acute kidney
      injury, but their role in chronic kidney diseases is still unknown. More
      specifically, it is not known whether MSCs halt fibrosis. The purpose of this
      work was to investigate the role of MSCs in fibrogenesis using a model of chronic
      renal failure. MSCs were obtained from the tibias and femurs of male Wistar-EPM
      rats. Female Wistar rats were subjected to the remnant model, and 2|x|10(5) MSCs
      were intravenously administrated to each rat every other week for 8 weeks or only
      once and followed for 12 weeks. SRY gene expression was observed in female rats
      treated with male MSCs, and immune localization of CD73(+)CD90(+) cells at 8
      weeks was also assessed. Serum and urine analyses showed an amelioration of
      functional parameters in MSC-treated animals at 8 weeks, but not at 12 weeks.
      Masson's trichrome and Sirius red staining demonstrated reduced levels of
      fibrosis in MSC-treated animals. These results were corroborated by reduced
      vimentin, type I collagen, transforming growth factor beta, fibroblast specific
      protein 1 (FSP-1), monocyte chemoattractant protein 1, and Smad3 mRNA expression
      and alpha smooth muscle actin and FSP-1 protein expression. Renal interleukin
      (IL)-6 and tumor necrosis factor alpha mRNA expression levels were significantly
      decreased after MSC treatment, whereas IL-4 and IL-10 expression levels were
      increased. All serum cytokine expression levels were decreased in MSC-treated
      animals. Taken together, these results suggested that MSC therapy can indeed
      modulate the inflammatory response that follows the initial phase of a chronic
      renal injury. The immunosuppressive and remodeling properties of MSCs may be
      involved in the decreased fibrosis in the kidney.

PMID- 19750538
TI  - Embryonic stem cells with GFP knocked into the dopamine transporter yield
      purified dopamine neurons in vitro and from knock-in mice.
AB  - Parkinson's disease (PD) is characterized by the selective loss of midbrain
      dopamine neurons. Neural transplantation with fetal dopamine neurons can be an
      effective therapy for patients with PD, but recovery of human fetal cells is
      difficult. Scarcity of tissue has limited clinical application to a small number
      of research subjects worldwide. Selective differentiation of embryonic stem cells
      (ESCs) to dopamine neurons could lead to an unlimited supply of cells for
      expanded clinical transplantation. To facilitate the differentiation and
      purification of dopamine neurons, the green fluorescent protein (GFP) gene was
      inserted into the dopamine transporter (DAT) locus in mouse ESCs using homologous
      recombination. From these DAT-GFP ESCs, dopamine neurons expressing GFP were
      successfully produced by in vitro differentiation. The DAT-GFP ESCs were used to
      generate DAT-GFP knock-in mice. We have found that GFP was colocalized with DAT,
      Pitx3, Engrailed-1, and tyrosine hydroxylase-positive cells in midbrain,
      hypothalamus, and olfactory bulb but not in noradrenergic cell regions or other
      ectopic sites. The GFP-positive dopamine neurons could be isolated from embryonic
      day-15 ventral midbrain by fluorescence activated cell sorting. These purified
      dopamine neurons survived reculture and expressed tyrosine hydroxylase and DAT
      when cocultured with mouse astrocytes or striatal cells. Animals homozygous for
      DAT-GFP were hyperactive because they had no functional DAT protein. These DAT
      GFP knock-in ESCs and mice provide unique tools for purifying dopamine neurons to
      study their physiology, pharmacology, and genetic profiles.

PMID- 19750537
TI  - Multipathway kinase signatures of multipotent stromal cells are predictive for
      osteogenic differentiation: tissue-specific stem cells.
AB  - Bone marrow-derived multipotent stromal cells (MSCs) offer great promise for
      regenerating tissue. Although certain transcription factors have been identified
      in association with tendency toward particular MSC differentiation phenotypes,
      the regulatory network of key receptor-mediated signaling pathways activated by
      extracellular ligands that induce various differentiation responses remains
      poorly understood. Attempts to predict differentiation fate tendencies from
      individual pathways in isolation are problematic due to the complex pathway
      interactions inherent in signaling networks. Accordingly, we have undertaken a
      multivariate systems approach integrating experimental measurement of multiple
      kinase pathway activities and osteogenic differentiation in MSCs, together with
      computational analysis to elucidate quantitative combinations of kinase signals
      predictive of cell behavior across diverse contexts. In particular, for culture
      on polymeric biomaterial surfaces presenting tethered epidermal growth factor,
      type I collagen, neither, or both, we have found that a partial least-squares
      regression model yields successful prediction of phenotypic behavior on the basis
      of two principal components comprising the weighted sums of eight intracellular
      phosphoproteins: phospho-epidermal growth factor receptor, phospho-Akt, phospho
      extracellular signal-related kinase 1/2, phospho-heat shock protein 27, phospho-c
      Jun, phospho-glycogen synthase kinase 3alpha/beta, phospho-p38, and phospho
      signal transducer and activator of transcription 3. This combination provides the
      strongest predictive capability for 21-day differentiated phenotype status when
      calculated from day-7 signal measurements; day-4 and day-14 signal measurements
      are also significantly predictive, indicating a broad time frame during MSC
      osteogenesis wherein multiple pathways and states of the kinase signaling network
      are quantitatively integrated to regulate gene expression, cell processes, and
      ultimately, cell fate.

PMID- 19750539
TI  - Direct imaging of immune rejection and memory induction by allogeneic mesenchymal
      stromal cells.
AB  - Although mesenchymal stromal cells (MSCs) exhibit marked immunoregulatory
      activity through multiple mechanisms, their potential to completely evade
      rejection upon transplantation into allogeneic recipients is controversial. To
      directly address this controversy, the survival of luciferase-labeled MSCs
      (Luc(+) MSCs) was evaluated by imaging in allogeneic recipients. This analysis
      showed that although MSCs exhibited longer survival compared to fibroblasts
      (Fib), their survival was significantly shorter compared to that exhibited in
      syngeneic or in immune-deficient Balb-Nude or non-obese diabetic severe combined
      immunodeficiency (NOD-SCID) recipients. Graft rejection in re-challenge
      experiments infusing Luc(+) Fib into mice, which had previously rejected Luc(+)
      MSCs, indicated potential induction of immune memory by the MSCs. This was
      further analyzed in T-cell antigen receptor (TCR) transgeneic mice in which
      either CD4 TEA mice or CD8 T cells (2C mice) bear a TCR transgene against a
      specific MHC I or MHC II, respectively. Thus, following a re-challenge with MSCs
      expressing the cognate MHC haplotype, an enhanced percentage of 2C CD8(+) or TEA
      CD4(+) T cells exhibited a memory phenotype (CD122(+), CD44(+), and CD62L(low)).
      Collectively, these results demonstrate that MSCs are not intrinsically immune
      privileged, and under allogeneic settings, these cells induce rejection, which is
      followed by an immune memory. Considering that the use of allogeneic or even a
      third party ("off the shelf") MSCs is commonly advocated for a variety of
      clinical applications, our results strongly suggest that long-term survival of
      allogeneic MSCs likely represents a major challenge.

PMID- 19750540
TI  - A novel role for gamma-secretase in the formation of primitive streak-like
      intermediates from ES cells in culture.
AB  - gamma-Secretase is a membrane-associated protease with multiple intracellular
      targets, a number of which have been shown to influence embryonic development and
      embryonic stem (ES) cell differentiation. This paper describes the use of the
      gamma-secretase inhibitor N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine
      t-butyl ester (DAPT) to evaluate the role of gamma-secretase in the
      differentiation of pluripotent stem cells to the germ lineages. The addition of
      DAPT did not prevent the formation of primitive ectoderm-like cells from ES cells
      in culture. In contrast, the addition of DAPT during primitive ectoderm-like cell
      differentiation interfered with the ability of both serum and BMP4 to induce a
      primitive streak-like intermediate and resulted in the preferential formation of
      neurectoderm. Similarly, DAPT reduced the formation of primitive streak-like
      intermediates from differentiating human ES cells; the culture conditions used
      resulted in a population enriched in human surface ectoderm. These data suggest
      that gamma-secretase may form part of the general pathway by which mesoderm is
      specified within the primitive streak. The addition of an E-cadherin neutralizing
      antibody was able to partially reverse the effect of DAPT, suggesting that DAPT
      may be preventing the formation of primitive streak-like intermediates and
      promoting neurectoderm differentiation by stabilizing E-cadherin and preventing
      its proteolysis.

PMID- 19750541
TI  - Camptocormia as a presentation of generalized inflammatory myopathy.
AB  - Camptocormia is an abnormal truncal flexion posture that occurs while walking or
      standing. It is usually caused by various hypokinetic movement disorders such as
      Parkinson disease and multiple system atrophy. Myopathy or motor neuron disease
      can also be infrequent causes of camptocormia. Paraspinous muscle biopsy usually
      reveals focal myositis, regardless of the etiology of camptocormia. We describe
      the first case of generalized inflammatory myopathy with prominent camptocormia
      and proximal muscle weakness. Muscle biopsy of the quadriceps confirmed the
      diagnosis of polymyositis, and the posture showed modest improvement in response
      to steroid treatment.

PMID- 19750542
TI  - Effect of superficial peroneal nerve fascial penetration site on nerve conduction
      studies.
AB  - Using nerve conduction studies (NCS) and ultrasonography, we sought to determine
      the stimulation site that corresponds to the site at which the superficial
      peroneal nerve (SPN) penetrates the fascia and yields the most accurate NCS
      results. NCS parameters of the SPN sensory nerve action potential (SNAP) were
      recorded from 37 legs at 14, 12, 9, 7, and 5 cm (S1, S2, S3, S4, and S5,
      respectively) proximal to the recording electrode, and analyzed by one-way
      analysis of variance. SPN penetration sites were visualized by ultrasonography.
      The mean SNAP amplitude/area (17.2 +/- 6.7 microV/9.6 +/- 4.6 microV/ms) at S3-S5
      differed significantly from that at S1-S2 (11.6 +/- 4.7 microV/9.2 +/- 4.4
      microV/ms) (F = 10.2, P < 0.001; F = 5.09, P = 0.0007). Ultrasonography showed
      that the SPN became subcutaneous between S3 and S4. Clinical application of these
      results should help in obtaining more accurate data during electrodiagnostic
      studies of conditions that involve the SPN.

PMID- 19750543
TI  - Evoked myotonia can be "dialed-up" by increasing stimulus train length in
      myotonic dystrophy type 1.
AB  - It is unknown how evoked myotonia varies with stimulus frequency or train length,
      or how it compares to voluntary myotonia in myotonic dystrophy type 1 (DM1).
      First dorsal interosseous (FDI) tetanic contractions evoked by trains of 10-20
      ulnar nerve stimuli at 10-50 HZ were recorded in 10 DM1 patients and 10 normals.
      For comparison, maximum voluntary handgrip contractions were also recorded. An
      automated computer program placed cursors along the declining (relaxation) phase
      of the force recordings at 90% and 5% of peak force (PF) and calculated
      relaxation times (RTs) between these points. For all stimulus frequencies and
      train lengths, evoked RTs were much shorter, and evoked PFs were much greater in
      normals than in DM1. In normals, evoked RT was independent of stimulus frequency
      and train length, while in DM1 RT was longer for train lengths of 20 stimuli
      (mean: 9 s in DM1; 0.20 in normals) than for 10 stimuli (mean: 3 s in DM1, 0.19
      in normals), but it did not change with stimulus frequency. In both groups PF
      increased greatly as stimulus frequency rose from 10-50 HZ but only slightly as
      train length rose from 10-20 stimuli. Voluntary handgrip RT (mean: 1.9 s) was
      less than evoked FDI RT (mean: 9 s). In DM1, evoked RT can be "dialed up" by
      increasing stimulus train length. Evoked myotonia testing utilizing a stimulus
      paradigm of at least 20 stimuli at 30-50 HZ may be useful in antimyotonic drug
      trials, particularly when grip RT is normal or equivocal.

PMID- 19750544
TI  - Limitations of the algorithm for the SAFE biopsy: a noninvasive fibrosis measure
      in chronic hepatitis C.

PMID- 19750545
TI  - Sensitive J-coupled metabolite mapping using Sel-MQC with selective multi-spin
      echo readout.
AB  - The selective multiple quantum coherence technique is combined with a read
      gradient to accelerate the measurement of a specific scalar-coupled metabolite.
      The sensitivities of the localization using pure phase encoding and localization
      with the read gradient are compared in experiments at high magnetic field
      strength (17.6 T). Multiple spin-echoes of the selective multiple quantum
      coherence edited metabolite are acquired using frequency-selective refocusing of
      the specified molecule group. The frequency-selective refocusing does not affect
      the J-modulation of a coupled spin system, and the echo time is not limited to a
      multiple of 1/J to acquire pure in-phase or antiphase signal. The multiple echoes
      can be used to accelerate the metabolite imaging experiment or to measure the
      apparent transverse relaxation T(2). A simple phase-shifting scheme is presented,
      which enables the suppression of editing artifacts resulting from the multiple
      spin-echoes of the water resonance. The experiments are carried out on phantoms,
      in which lactate and polyunsaturated fatty acids are edited, and in vivo on
      tumors, in which lactate content and T(2) are imaged. The method is of particular
      interest when a fast and sensitive selective multiple quantum coherence editing
      is necessary, e.g., for spatial three dimensional experiments.

PMID- 19750546
TI  - Sonography and fine-needle aspiration biopsy in the diagnosis of benign versus
      malignant nodules in patients with autoimmune thyroiditis.
AB  - PURPOSE: To correlate sonographic (US) characteristics and results of fine-needle
      aspiration biopsy (FNAB) of thyroid nodules in autoimmune thyroiditis (AT) with
      surgical pathological findings. METHOD: Forty AT patients with 40 nodular lesions
      were analyzed retrospectively. Five sonographic characteristics were recorded for
      each nodule: diameter, echogenicity, microcalcification, halo sign, and margin.
      Preoperative sonograms and FNAB results were compared with postoperative
      histopathological findings. RESULT: Twenty-four of the 40 nodules were malignant,
      including 20 papillary carcinomas, 3 follicular carcinomas, and 1 medullary
      carcinoma. Of the 16 benign nodules, 8 were nodular hyperplasia, 6 lymphocytic
      thyroiditis, and 1 each follicular adenoma and Hurthle cell adenoma. The only US
      parameter that was significant in malignant vs. benign nodules was the presence
      of poorly defined margins. Based on preoperative cytology, 22 of the 23 malignant
      nodules were correctly diagnosed, and 10 of the 14 benign nodules were correctly
      identified. The positive predictive value was 78.6%, and the negative predictive
      value was 93.7%. CONCLUSION: No single US parameter can predict thyroid
      malignancy in patients with AT. A combination of US and FNAB provides the most
      sensitive and specific approach available preoperatively.

PMID- 19750547
TI  - Use of (S)-BINOL as NMR chiral solvating agent for the enantiodiscrimination of
      omeprazole and its analogs.
AB  - The application of (S)-1,1'-binaphthyl-2,2'-diol as NMR chiral solvating agent
      (CSA) for omeprazole, and three of its analogs (lanso-, panto-, and rabe-prazole)
      was investigated. The formation of diastereomeric host-guest complexes in
      solution between the CSA and the racemic substrates produced sufficient NMR
      signal splitting for the determination of enantiomeric excesses by (1)H- or (19)F
      NMR spectroscopy. Using of hydrophobic deuterated solvents was mandatory for
      obtaining good enantiodiscrimination, thus suggesting the importance of
      intermolecular hydrogen bonds in the stabilization of the complexes. The method
      was applied to the fast quantification of the enantiomeric purity of in-process
      samples of S-omeprazole.

PMID- 19750548
TI  - The phytoecdysteroid profiles of 7 species of Silene (Caryophyllaceae).
AB  - The phytoecdysteroid profiles of extracts of aerial parts of flowering plants of
      7 ecdysteroid-containing species in the genus Silene (Caryophyllaceae; S.
      fridvaldszkyana Hampe, S. gigantea L., S. graminifolia Otth, S. mellifera Boiss.
      & Reuter, S. repens Patr., S. schmuckeri Wettst., and S. sendtneri Boiss.) have
      been examined and identified by HPLC and, in the case of two new compounds, by
      mass spectrometry and NMR. S. frivaldszkyana was found to contain predominantly
      20-hydroxyecdysone (20E), with smaller amounts of 2-deoxyecdysone (2dE), 2-deoxy
      20-hydroxyecdysone (2d20E), polypodine B (polB), integristerone A (IntA), 26
      hydroxypolypodine B (26polB), and 20,26-dihydroxyecdysone (20,26E). Additionally,
      a new minor ecdysteroid, 26-hydroxyintegristerone A, has been identified from
      this species. S. gigantea contains 3 major ecdysteroids (2dE, 2d20E, and 20E) and
      much smaller amounts of intA and 2-deoxy-20-hydroxyecdysone 25-beta-D-glucoside,
      which is a new ecdysteroid. Ecdysteroids in the other 5 species have been
      identified by co-chromatography with reference compounds on RP- and NP-HPLC
      systems. There is considerable variability with regard to ecdysteroid profiles
      within the genus Silene. The chemotaxonomic value of ecdysteroid profiles within
      the genus Silene is discussed.

PMID- 19750549
TI  - DNA-binding properties of Drosophila ecdysone receptor isoforms and their
      modification by the heterodimerization partner ultraspiracle.
AB  - Transcriptional activity of ecdysone receptor (EcR) isoforms varies considerably
      and is modified further by the heterodimerization partner and hormone treatment.
      To investigate whether differences in DNA binding of receptor complexes are
      responsible for these variations in transcriptional activity, interaction of
      Drosophila EcR isoforms, and variants of Ultraspiracle (Usp), the orthologue of
      RXR, with the ecdysone response elements (EcRE) hsp 27, PAL-1, and DR-1, were
      determined by electrophoretic mobility shift assays. Receptor proteins were
      expressed in vertebrate cells (CHO-K1) in order to rule out an influence of
      endogenous receptor proteins. In the absence of a heterodimerization partner,
      weak DNA binding of EcR was detected even without hormone with EcR-A and -B1, but
      not EcR-B2. In the presence of hormone, all three isoforms show increased binding
      to the hsp 27 EcRE. The heterodimerization partner Usp increased DNA binding
      considerably. The hormone effect of heterodimers is more pronounced with both EcR
      B isoforms compared to EcR-A. Two specific bands were obtained for EcR-A and B1
      but only one band is visible with EcR-B2. Deletion of the C-domain of Usp still
      allows basal DNA binding of the heterodimer, but in contrast to full-length Usp,
      addition of hormone decreases the intensity of the retarded receptor band of all
      EcR isoforms and the EcREs hsp27 and DR-1 considerably, whereas interaction with
      the EcRE PAL-1 is only slightly affected. Synergistic effects on transcriptional
      activity are associated with the formation of different receptor DNA-complexes
      observed with 1xhsp27 and 3xhsp27. Comparison of DNA-binding properties of EcR
      isoforms and EcR/Usp heterodimers revealed that binding of receptor complexes to
      hsp 27 EcRE is dependent on the AB domain of EcR and the AB-, C-, and D-domains
      of the heterodimerization partner. Interaction with the hsp 27 EcRE correlates
      neither with ligand binding nor with transcriptional activity of the various
      receptor complexes. We, therefore, conclude that the different receptor functions
      are regulated separately, for example, by interaction with co-modulators or post
      transcriptional modifications.

PMID- 19750550
TI  - Characterization of alternatively spliced transcripts encoding heat shock
      transcription factor in cultured cells of the cabbage armyworm, Mamestra
      brassicae.
AB  - A gene encoding heat shock transcription factor (HSF) was cloned and sequenced
      from cultured cells of the cabbage armyworm, Mamestra brassicae. The cDNA
      potentially encoded a 699-aa protein, with a calculated molecular weight of 77.8
      kDa. Deduced amino acid identities to HSFs from Aedes aegypti and Drosophila
      melanogaster were 36 and 34%, respectively. Analysis of the genomic DNA revealed
      eight exons and three optional exons: a, b, and c. Exon a contained a premature
      in-frame stop codon that would generate a truncated protein. When the cells were
      exposed to high temperature or cadmium, no particular alternative transcripts
      showed significant up- or down-regulated expression relative to the total amount
      of the transcripts. These results suggest that alternative splicing may not be a
      principal mechanism for regulation of M. brassicae HSF gene expression in
      response to heat shock and cadmium.

PMID- 19750551
TI  - Phytoecdysteroid C2-hydroxylase is microsomal in spinach, Spinacia oleracea L.
AB  - An enzyme involved in the biosynthesis of phytoecdysteroids, the C2-hydroxylase,
      has been investigated in spinach, Spinacia oleracea. This enzyme is microsomal
      and its K(m) has been determined using 2-deoxy-20-hydroxyecdysone as substrate
      (K(m)=3.72 microM). It is much more efficient with 2-deoxy-20-hydroxyecdysone
      than with 2-deoxyecdysone and, conversely, the C20-hydroxylase is more active on
      2-deoxyecdysone than on ecdysone. These data support the conclusion that C20
      hydroxylation precedes C2-hydroxylation. The C2-hydroxylase is inhibited by high
      concentrations of 20E. Substrate specificity and subcellular localization of C2
      hydroxylase differ between plants and insects, and these data, as well as those
      previously reported on other biosynthetic steps, show the great difference
      between plant and insect ecdysteroid biosynthetic pathways and suggest an
      independent origin for the pathways in both kingdoms.

PMID- 19750553
TI  - Subtypes of panic attacks: a critical review of the empirical literature.
AB  - BACKGROUND: Panic disorder is a heterogeneous disorder, comprising a variety of
      somatic, physiological, and cognitive symptoms during repeated panic attacks. As
      a result, considerable data have examined whether panic attacks may be classified
      into distinct diagnostic or functional subtypes. The aim of this study is to
      evaluate the existing literature regarding the validity of panic attack subtypes.
      METHODS: This review focuses on data published since 2000, with the publication
      of DSM-IV-TR, augmented by replicated data published since 1980, with the
      publication of DSM-III and subsequently DSM-IV. Published reports evaluating
      empirical evidence for the validity of panic attack subtypes are reviewed.
      RESULTS: Five sets of panic symptoms (respiratory, nocturnal, nonfearful,
      cognitive, and vestibular) have been shown to cluster together at varying degrees
      of consistency. However, none of these potential subtypes have been associated
      with sufficient and reliable external validation criteria indicative of
      functional differences. This apparent lack of findings may be related to
      methodological inconsistencies or limitations across the reviewed studies.
      CONCLUSIONS: Although at present the data do not warrant the utility of
      subtyping, further research aimed at patent gaps in the literature, including
      clearer operationalization of symptom subtypes, greater use of biological
      challenge paradigms and physiological and other more objective measures of fear
      and anxiety, and exploration of subtyping based on biological factors such as
      genetics, may support the future designation of panic attack subtypes and their
      ultimate clinical utility.

PMID- 19750552
TI  - Risk and resilience: genetic and environmental influences on development of the
      stress response.
AB  - Exposure to stressful events during development has consistently been shown to
      produce long-lasting alterations in the hypothalamic-pituitary-adrenal (HPA)
      axis, which may increase vulnerability to disease, including posttraumatic stress
      disorder and other mood and anxiety disorders. Recently reported genetic
      association studies indicate that these effects may be mediated, in part, by
      genexenvironment interactions involving polymorphisms within two key genes, CRHR1
      and FKBP5. Data suggest that these genes regulate HPA axis function in
      conjunction with exposure to child maltreatment or abuse. In addition, a large
      and growing body of preclinical research suggests that increased activity of the
      amygdala-HPA axis induced by experimental manipulation of the amygdala mimics
      several of the physiological and behavioral symptoms of stress-related
      psychiatric illness in humans. Notably, interactions between the developing
      amygdala and HPA axis underlie critical periods for emotional learning, which are
      modulated by developmental support and maternal care. These translational
      findings lead to an integrated hypothesis: high levels of early life trauma lead
      to disease through the developmental interaction of genetic variants with neural
      circuits that regulate emotion, together mediating risk and resilience in adults.

PMID- 19750554
TI  - Childhood maltreatment linked to greater symptom severity and poorer quality of
      life and function in social anxiety disorder.
AB  - BACKGROUND: There is a paucity of data examining the prevalence and impact of
      childhood maltreatment in patients presenting with a primary diagnosis of social
      anxiety disorder (SAD). We thus examined the presence of a broad spectrum of
      childhood maltreatment, including physical, sexual, and emotional abuse and
      neglect, in treatment-seeking individuals with the generalized subtype of SAD
      (GSAD). We hypothesized that a history of childhood maltreatment would be
      associated with greater SAD symptom severity and poorer associated function.
      METHODS: One hundred and three participants with a primary diagnosis of GSAD
      (mean age 37+/-14; 70% male) completed the well-validated, self-rated Childhood
      Trauma Questionnaire (CTQ), as well as measures of SAD symptom severity and
      quality of life. RESULTS: Fully 70% (n=72) of the GSAD sample met severity
      criteria for at least one type of childhood abuse or neglect as measured by the
      CTQ subscales using previously established thresholds. CTQ total score adjusted
      for age and gender was associated with greater SAD severity, and poorer quality
      of life, function, and resilience. Further, the number of types of maltreatment
      present had an additive effect, with specific associations for emotional abuse
      and neglect with SAD severity. CONCLUSIONS: Despite the use of validated
      assessments, our findings are limited by the retrospective and subjective nature
      of self-report measures used to assess childhood maltreatment. Nonetheless, these
      data suggest a high rate of childhood maltreatment in individuals seeking
      treatment for GSAD, and the association of maltreatment with greater disorder
      severity suggests that screening is clinically prudent.

PMID- 19750555
TI  - Genetic and environmental influences on the co-morbidity between depression,
      panic disorder, agoraphobia, and social phobia: a twin study.
AB  - BACKGROUND: Major depression (MD) and anxiety disorders such as panic disorder
      (PD), agoraphobia (AG), and social phobia (SP) are heritable and highly co
      morbid. However, the relative importance of genetic and environmental etiology of
      the covariation between these disorders, particularly the relationship between PD
      and AG, is less clear. METHODS: This study measured MD, PD, and AG in a
      population sample of 5,440 twin pairs and 1,245 single twins, about 45% of whom
      were also scored for SP. Prevalences, within individual co-morbidity and twin
      odds ratios for co-morbidity, are reported. A behavioral genetic analysis of the
      four disorders using the classical twin design was conducted. RESULTS: Odds
      ratios for MD, PD, AG, and SP in twins of individuals diagnosed with one of the
      four disorders were increased. Heritability estimates under a threshold-liability
      model for MD, PD, AG, and SP respectively were .33 (CI: 0.30-0.42), .38 (CI: 0.24
      0.55), .48 (CI: 0.37-0.65), and .39 (CI: 0.16-0.65), with no evidence for any
      variance explained by the common environment shared by twins. We find that a
      common genetic factor explains a moderate proportion of variance in these four
      disorders. The genetic correlation between PD and AG was .83. CONCLUSION: MD, PD,
      AG, and SP strongly co-aggregate within families and common genetic factors
      explain a moderate proportion of variance in these four disorders. The high
      genetic correlation between PD and AG and the increased odds ratio for PD and AG
      in siblings of those with AG without PD suggests a common genetic etiology for PD
      and AG.

PMID- 19750556
TI  - Carotid- intima media thickness is independently associated with cognitive
      decline. The INVADE study.
AB  - OBJECTIVES: Increased carotid intima-media thickness (C-IMT) is a non-invasive
      marker of atherosclerosis and predicts vascular events. Moreover, increasing
      evidence suggests an association between carotid atherosclerosis and cognitive
      decline. The purpose of this study is to investigate the relationship between C
      IMT and the development of cognitive impairment in a large population-based
      sample. METHODS: This study was based on the data of the participants of the
      INVADE (Intervention project on cerebrovascular diseases and dementia in the
      district of Ebersberg, Bavaria) project. Vascular risk factors, Geriatric
      depression scale (GDS) and "6 Item Cognitive Impairment Test" (6CIT) were
      evaluated at baseline and after 2 years. The relationship between C-IMT and
      cognitive impairment was analysed using multivariate logistic regression.
      RESULTS: Complete baseline data were available in 3386 subjects (mean age 67.7
      [95% confidence interval (CI): 67.5, 68.0] years, 41% male). During follow-up,
      174 subjects developed a new cognitive impairment. In the subgroup without
      cognitive impairment at baseline a significant association between cognitive
      decline after 2 years and elevated C-IMT at baseline could be detected with a
      significantly higher baseline C-IMT in those with cognitive decline (0.87 mm vs.
      0.78 mm; p < 0.0001). After adjustment for various risk factors only age, GDS
      baseline 6CIT and C-IMT were independently associated with the development of a
      new cognitive impairment. CONCLUSIONS: Our data indicate that an increased
      carotid intima-media thickness predicts a cognitive decline in an elderly
      population without prevalent cognitive impairment.

PMID- 19750557
TI  - Duloxetine and care management treatment of older adults with comorbid major
      depressive disorder and chronic low back pain: results of an open-label pilot
      study.
AB  - OBJECTIVE: In older adults, major depressive disorder (MDD) and chronic low back
      pain (CLBP) are common and mutually exacerbating. We predicted that duloxetine
      pharmacotherapy and Depression and Pain Care Management (DPCM) would result in
      (1) significant improvement in MDD and CLBP and (2) significant improvements in
      health-related quality of life, anxiety, disability, self-efficacy, and sleep
      quality. DESIGN AND INTERVENTION: Twelve week open-label study using duloxetine
      up to 120 mg/day + DPCM. SETTING: Outpatient late-life depression research
      clinic. PATIENTS: Thirty community-dwelling adults >60 years old. OUTCOME
      MEASURES: Montgomery Asberg Depression Rating Scale (MADRS) and McGill Pain
      Questionnaire-Short Form (MPQ-SF). RESULTS: 46.7% (n = 14) of the sample had a
      depression remission. All subjects who met criteria for the depression remission
      also had a pain response. 93.3% (n = 28) had a significant pain response. Of the
      subjects who met criteria for a low back pain response, 50% (n = 14) also met
      criteria for the depression remission. The mean time to depression remission was
      7.6 (SE = 0.6) weeks. The mean time to pain response was 2.8 (SE = 0.5) weeks.
      There were significant improvements in mental health-related quality of life,
      anxiety, sleep quality, somatic complaints, and both self-efficacy for pain
      management and for coping with symptoms. Physical health-related quality of life,
      back pain-related disability, and self-efficacy for physical functioning did not
      improve. CONCLUSIONS: Serotonin and norepinephrine reuptake inhibitors like
      duloxetine delivered with DPCM may be a good choice to treat these linked
      conditions in older adults. Treatments that target low self-efficacy for physical
      function and improving disability may further increase response rates.

PMID- 19750558
TI  - Willingness-to-pay for reductions in care need: estimating the value of informal
      care in Alzheimer's disease.
AB  - OBJECTIVE: To estimate the value of informal care in Alzheimer's disease using
      contingent valuation. METHODS: A questionnaire was administered to 517 primary
      carers in four countries (UK, Spain, Sweden, and US). Dichotomous choice and
      bidding game methods were used to elicit their willingness to pay for a reduction
      in care burden by 1 h per day, or a total elimination of care needs. Further, the
      relationship between carer willingness to pay and carer and patient
      characteristics including disease severity and income was examined. RESULTS:
      Carers spend on average about 7-9 h per day on giving care to their patient, of
      which 4-5 h constituted basic and instrumental ADL tasks. For a 1 h reduction in
      need for care per day, carers in the UK, Spain, Sweden, and US said that they
      were willing to pay pound105, pound121, pound59, and pound144 per month
      respectively. The willingness to pay was higher for carers with higher disposable
      income while the influence of other determinants varied across countries. About
      one-third of carers were not willing to pay anything for a reduction in care.
      CONCLUSIONS: Carers' stated willingness to pay for reductions in care giving time
      is substantial and comparable to the prices currently paid for treatments that
      achieve this benefit. Its determinants seem more directly related to carer status
      than directly to patient status and may vary by region and by cultural and
      sociologic factors.

PMID- 19750560
TI  - The effect of alcohol and tobacco consumption, and apolipoprotein E genotype, on
      the age of onset in Alzheimer's disease.
AB  - OBJECTIVE: This study examined the association between a history of heavy alcohol
      use and smoking, presence of the apolipoprotein-E epsilon 4 allele (APOE
      epsilon4), and age of disease onset in a community dwelling sample of 685
      Alzheimer's disease (AD) patients spanning three ethnic groups. DESIGN: Cross
      sectional study of AD patients evaluated at a University-affiliated outpatient
      memory disorders clinic. SUBJECTS: A clinic-based cohort of white non-Hispanic
      (WNH; n = 397), white Hispanic (WH; n = 264), and African-American (AA; n = 24)
      patients diagnosed with possible or probable AD according to NINCDS-ADRDA
      diagnostic criteria. MEASUREMENTS: The age of onset of AD was obtained from a
      knowledgeable family member. All patients were assessed for APOE genotype.
      History of alcohol and tobacco consumption prior to the onset of dementia was
      obtained via an interview with the patient and the primary caregiver. A history
      of heavy drinking was defined as >2 drinks per day and a history of heavy smoking
      was defined as > or =1 pack per day. RESULTS: Presence of an APOE epsilon4
      allele, a history of heavy drinking, or a history of heavy smoking were each
      associated with an earlier onset of AD by 2-3 years. Patients with all three risk
      factors were likely to be diagnosed with AD nearly 10 years earlier than those
      with none of the risk factors. CONCLUSION: The results suggest that APOE epsilon4
      and heavy drinking and heavy smoking lower the age of onset for AD in an additive
      fashion.

PMID- 19750559
TI  - Viruses and autophagy.
AB  - Autophagy is an evolutionarily conserved intracellular process by which bulk
      cytoplasm is enveloped inside a double-membraned vesicle and shuttled to
      lysosomes for degradation. Within the last 15 years, the genes necessary for the
      execution of autophagy have been identified and the number of tools for studying
      this process has grown. Autophagy is essential for tissue homeostasis and
      development and defective autophagy is associated with a number of diseases. As
      intracellular parasites, during the course of an infection, viruses encounter
      autophagy and interact with the proteins that execute this process. Autophagy
      and/or autophagy genes likely play both anti-viral and pro-viral roles in the
      life cycles and pathogenesis of many different virus families. With respect to
      anti-viral roles, the autophagy proteins function in targeting viral components
      or virions for lysosomal degradation in a process termed xenophagy, and they also
      play a role in the initiation of innate and adaptive immune system responses to
      viral infections. Consistent with this anti-viral role of host autophagy, some
      viruses encode virulence factors that interact with the host autophagy machinery
      and block the execution of autophagy. In contrast, other viruses appear to
      utilise components of the autophagic machinery to foster their own intracellular
      growth or non-lytic cellular egress. As the details of the role (s) of autophagy
      in viral pathogenesis become clearer, new anti-viral therapies could be developed
      to inhibit the beneficial and enhance the destructive aspects of autophagy on the
      viral life cycle.

PMID- 19750561
TI  - Maturation of the HIV reverse transcription complex: putting the jigsaw together.
AB  - Upon HIV attachment, fusion and entry into the host cell cytoplasm, the viral
      core undergoes rearrangement to become the mature reverse transcription complex
      (RTC). Reduced infectivity of viral deletion mutants of the core proteins, capsid
      and negative factor (Nef), can be complemented by vesicular stomatitis virus
      (VSV) pseudotyping suggesting a role for these viral proteins in a common event
      immediately post-entry. This event may be necessary for correct trafficking of
      the early complex. Enzymatic activation of the complex occurs either before or
      during RTC maturation, and may be dependent on the presence of deoxynucleotides
      in the host cell. The RTC initially becomes enlarged immediately after entry,
      which is followed by a decrease in its sedimentation rate consistent with core
      uncoating. Several HIV proteins associated with the RTC and recently identified
      host-cell proteins are important for reverse transcription while genome-wide
      siRNA knockdown studies have identified additional host cell factors that may be
      required for reverse transcription. Determining precisely how these proteins
      assist the RTC function needs to be addressed.

PMID- 19750562
TI  - Relationships between early maladaptive schemas and psychosocial developmental
      task resolution.
AB  - In schema therapy, early maladaptive schemas (EMS) are hypothesized to be the
      result of adverse relational experiences in childhood that hinder the resolution
      of important psychological developmental tasks. The purpose of the present study
      was to examine the relationships between EMS and the resolution of the
      developmental tasks that are described in Erikson's scheme of personality
      development. One hundred and forty-five adult psychiatric outpatients completed
      measures of EMS and resolution of psychosocial development tasks at two
      occasions. Results from correlational and regression analyses showed that EMS are
      generally associated with unsuccessful psychosocial task resolution. Furthermore,
      schema change predicted changes in the resolution of developmental tasks. These
      findings give support to Young's theory of schema development.

PMID- 19750563
TI  - The role of dendritic cells in alphaherpesvirus infections: archetypes and
      paradigms.
AB  - Dendritic cells (DCs) play a critical role in orchestrating both innate and
      adaptive components of the immune system and are therefore of pivotal importance
      in the initiation of immune responses to control and eliminate viral infections.
      A major focus of this review is to give an overview on the recent findings that
      point out the importance of DCs in controlling alphaherpesvirus infections, but
      also indicate that these viruses have evolved several strategies to inhibit
      and/or exploit DC functions to delay or escape elimination by the immune system.
      In addition, we point out the common features and interspecies differences
      between DCs from man and animal, and discuss the potential use of animal
      alphaherpesvirus homologues to gain further insights into the interaction between
      alphaherpesviruses and DCs in their natural virus-host environment. Finally,
      recent knowledge on the potential of alphaherpesviruses as vectors for DC
      stimulation and their use for immunotherapy is presented.

PMID- 19750564
TI  - MPR1 as a novel selection marker in Saccharomyces cerevisiae.
AB  - L-Azetidine-2-carboxylic acid (AZC) is a toxic four-membered ring analogue of L
      proline that is transported into cells by proline transporters. AZC and L-proline
      in the cells are competitively incorporated into nascent proteins. When AZC is
      present in a minimum medium, misfolded proteins are synthesized in the cells,
      thereby inhibiting cell growth. The MPR1 gene has been isolated from the budding
      yeast Saccharomyces cerevisiae Sigma1278b as a multicopy suppressor of AZC
      induced growth inhibition. MPR1 encodes a novel acetyltransferase that detoxifies
      AZC via N-acetylation. Since MPR1 is absent in the laboratory strain of S.
      cerevisiae S288C, it could be a positive selection marker that confers AZC
      resistance in the S288C background strains. To examine the usefulness of MPR1, we
      constructed some plasmid vectors that harboured MPR1 under the control of various
      promoters and introduced them into the S288C-derived strains. The expression of
      MPR1 conferred AZC resistance that was largely dependent on the expression level
      of MPR1. In an additional experiment, the galactose-inducible MPR1 and ppr1(+),
      the fission yeast Schizosaccharomyces pombe homologue of MPR1, were used for gene
      disruption by homologous recombination, and here AZC-resistant colonies were also
      successfully selected. We concluded that our MPR1-AZC system provides a powerful
      tool for yeast transformation.

PMID- 19750565
TI  - Overview of immunosuppression in liver transplantation.
AB  - Continued advances in surgical techniques and immunosuppressive therapy have
      allowed liver transplantation to become an extremely successful treatment option
      for patients with end-stage liver disease. Beginning with the revolutionary
      discovery of cyclosporine in the 1970s, immunosuppressive regimens have evolved
      greatly and current statistics confirm one-year graft survival rates in excess of
      80%. Immunosuppressive regimens include calcineurin inhibitors, anti-metabolites,
      mTOR inhibitors, steroids and antibody-based therapies. These agents target
      different sites in the T cell activation cascade, usually by inhibiting T cell
      activation or via T cell depletion. They are used as induction therapy in the
      immediate peri- and post-operative period, as long-term maintenance medications
      to preserve graft function and as salvage therapy for acute rejection in liver
      transplant recipients. This review will focus on existing immunosuppressive
      agents for liver transplantation and consider newer medications on the horizon.

PMID- 19750566
TI  - Prevalence, predictors, and clinical consequences of medical adherence in IBD:
      how to improve it?
AB  - Inflammatory bowel diseases (IBD) are chronic diseases with a relapsing-remitting
      disease course necessitating lifelong treatment. However, non-adherence has been
      reported in over 40% of patients, especially those in remission taking
      maintenance therapies for IBD. The economical impact of non-adherence to medical
      therapy including absenteeism, hospitalization risk, and the health care costs in
      chronic conditions, is enormous. The causes of medication non-adherence are
      complex, where the patient-doctor relationship, treatment regimen, and other
      disease-related factors play key roles. Moreover, subjective assessment might
      underestimate adherence. Poor adherence may result in more frequent relapses, a
      disabling disease course, in ulcerative colitis, and an increased risk for
      colorectal cancer. Improving medication adherence in patients is an important
      challenge for physicians. Understanding the different patient types, the reasons
      given by patients for non-adherence, simpler and more convenient dosage regimens,
      dynamic communication within the health care team, a self-management package
      incorporating enhanced patient education and physician-patient interaction, and
      identifying the predictors of non-adherence will help devise suitable plans to
      optimize patient adherence. This editorial summarizes the available literature on
      frequency, predictors, clinical consequences, and strategies for improving
      medical adherence in patients with IBD.

PMID- 19750568
TI  - Emerging treatments for complex perianal fistula in Crohn's disease.
AB  - Complex perianal fistulas have a negative impact on the quality of life of
      sufferers and should be treated. Correct diagnosis, characterization and
      classification of the fistulas are essential to optimize treatment. Nevertheless,
      in the case of patients whose fistulas are associated with Crohn's disease,
      complete closure is particularly difficult to achieve. Systemic medical
      treatments (antibiotics, thiopurines and other immunomodulatory agents, and, more
      recently, anti-tumor necrosis factor-alpha agents such as infliximab) have been
      tried with varying degrees of success. Combined medical (including infliximab)
      and less aggressive surgical therapy (drainage and seton placement) offer the
      best outcomes in complex Crohn's fistulas while more aggressive surgical
      procedures such as fistulotomy or fistulectomy may increase the risk of
      incontinence. This review will focus on emerging novel treatments for perianal
      disease in Crohn's patients. These include locally applied infliximab or
      tacrolimus, fistula plugs, instillation of fibrin glue and the use of adult
      expanded adipose-derived stem cell injection. More well-designed controlled
      studies are required to confirm the effectiveness of these emerging treatments.

PMID- 19750569
TI  - Meta-analysis and systematic review of colorectal endoscopic mucosal resection.
AB  - AIM: To evaluate the proportion of successful complete cure en-bloc resections of
      large colorectal polyps achieved by endoscopic mucosal resection (EMR). METHODS:
      Studies using the EMR technique to resect large colorectal polyps were selected.
      Successful complete cure en-bloc resection was defined as one piece margin-free
      polyp resection. Articles were searched for in Medline, Pubmed, and the Cochrane
      Control Trial Registry, among other sources. RESULTS: An initial search
      identified 2620 reference articles, from which 429 relevant articles were
      selected and reviewed. Data was extracted from 25 studies (n = 5221) which met
      the inclusion criteria. All the studies used snares to perform EMR. Pooled
      proportion of en-bloc resections using a random effect model was 62.85% (95% CI:
      51.50-73.52). The pooled proportion for complete cure en-bloc resections using a
      random effect model was 58.66% (95% CI: 47.14-69.71). With higher patient load (>
      200 patients), this complete cure en-bloc resection rate improves from 44.19%
      (95% CI: 24.31-65.09) to 69.17% (95% CI: 51.11-84.61). CONCLUSION: EMR is an
      effective technique for the resection of large colorectal polyps and offers an
      alternative to surgery.

PMID- 19750570
TI  - Sirolimus, bevacizumab, 5-Fluorouracil and irinotecan for advanced colorectal
      cancer: a pilot study.
AB  - AIM: To evaluate the efficacy and the safety of combined 5-Fluorouracil,
      irinotecan, bevacizumab and sirolimus in refractory advanced colorectal
      carcinoma. METHODS: We initiated a regimen with at day 1 an injection (iv) of
      bevacizumab at 5 mg/kg, followed by 180 mg/m(2) irinotecan, followed by
      Leucovorin 400 mg/m(2), followed by a 5-Fluorouracil bolus 400 mg/m(2); and a 46
      h infusion 2400 mg/m(2). Sirolimus was given orally as continuous administration
      of 2 mg twice a day every days. This treatment was repeated every 14 d. RESULTS:
      A total of 12 patients were enrolled. All patients presented with metastatic
      disease that had failed at least three lines of chemotherapy that contained
      oxaliplatin, irinotecan and bevacizumab. Cetuximab failure was also observed in
      all K-Ras wild-type patients. The median number of cycles was 8.5 (range 2-20)
      and clinical benefit was observed in eight patients. The median time to
      progression was 5 mo and the median survival was 8 mo. Grade 3 neutropenia
      developed in four patients, and grade 3 diarrhea and stomatitis in two.
      CONCLUSION: The combination regimen of 5-Fluorouracil, irinotecan, bevacizumab
      and sirolimus in advanced colorectal carcinoma after failure of classical
      treatment is feasible and promising. Further evaluation of this combination is
      required.

PMID- 19750567
TI  - Advances in diagnosis, treatment and palliation of cholangiocarcinoma: 1990-2009.
AB  - Several advances in diagnosis, treatment and palliation of cholangiocarcinoma
      (CC) have occurred in the last decades. A multidisciplinary approach to this
      disease is therefore recommended. CC is a relatively rare tumor and the main risk
      factors are: chronic inflammation, genetic predisposition and congenital
      abnormalities of the biliary tree. While the incidence of intra-hepatic CC is
      increasing, the incidence of extra-hepatic CC is trending down. The only curative
      treatment for CC is surgical resection with negative margins. Liver
      transplantation has been proposed only for selected patients with hilar CC that
      cannot be resected who have no metastatic disease after a period of neoadjuvant
      chemo-radiation therapy. Magnetic resonance imaging/magnetic resonance
      cholangiopancreatography, positron emission tomography scan, endoscopic
      ultrasound and computed tomography scans are the most frequently used modalities
      for diagnosis and tumor staging. Adjuvant therapy, palliative chemotherapy and
      radiotherapy have been relatively ineffective for inoperable CC. For most of
      these patients biliary stenting provides effective palliation. Photodynamic
      therapy is an emerging palliative treatment that seems to provide pain relief,
      improve biliary patency and increase survival. The clinical utility of other
      emerging therapies such as transarterial chemoembolization, hepatic arterial
      chemoinfusion and high intensity intraductal ultrasound needs further study.

PMID- 19750571
TI  - Effect of early propranolol administration on portal hypertensive gastropathy in
      cirrhotic rats.
AB  - AIM: To investigate any protective effect of early propranolol administration in
      the development of portal hypertensive gastropathy in cirrhotic rats. METHODS:
      For the development of liver cirrhosis and portal hypertensive gastropathy, 60
      rats underwent ligation of the left adrenal vein and complete devascularization
      of the left renal vein, followed by phenobarbital and carbon tetrachloride
      (CCl(4)) administration. After two weeks of CCl(4) administration, the rats were
      randomly separated into two groups. In group A, propranolol was continuously
      administered intragastrically throughout the study, whereas in group B normal
      saline (placebo) was administered instead. Hemodynamic studies and vascular
      morphometric analysis of gastric sections were performed after complete induction
      of cirrhosis. RESULTS: Vascular morphometric studies showed higher numbers of
      vessels in all mucosal layers in the control group. Statistical analysis revealed
      a significantly higher total vascular surface in the control group compared to
      the propranolol group, but with no statistically significant difference between
      the mean vascular surfaces between the groups. Our study clearly shows that the
      increased mucosal blood flow is manifested by a marked increase of vessel count.
      CONCLUSION: Early propranolol's administration in portal hypertensive cirrhotic
      rats seems to prevent intense gastric vascular congestion that characterizes
      portal hypertensive gastropathy.

PMID- 19750572
TI  - Does Helicobacter pylori eradication therapy for peptic ulcer prevent gastric
      cancer?
AB  - AIM: To investigate the effects of Helicobacter pylori (H pylori) eradication
      therapy for treatment of peptic ulcer on the incidence of gastric cancer.
      METHODS: A multicenter prospective cohort study was conducted between November
      2000 and December 2007 in Yamagata Prefecture, Japan. The study included patients
      with H pylori-positive peptic ulcer who decided themselves whether to receive H
      pylori eradication (eradication group) or conventional antacid therapy (non
      eradication group). Incidence of gastric cancer in the two groups was determined
      based on the results of annual endoscopy and questionnaire surveys, as well as
      Yamagata Prefectural Cancer Registry data, and was compared between the two
      groups and by results of H pylori therapy. RESULTS: A total of 4133 patients aged
      between 13 and 91 years (mean 52.9 years) were registered, and 56 cases of
      gastric cancer were identified over a mean follow-up of 5.6 years. The sex- and
      age-adjusted incidence ratio of gastric cancer in the eradication group, as
      compared with the non-eradication group, was 0.58 (95% CI: 0.28-1.19) and ratios
      by follow-up period (< 1 year, 1-3 years, > 3 years) were 1.16 (0.27-5.00), 0.50
      (0.17-1.49), and 0.34 (0.09-1.28), respectively. Longer follow-up tended to be
      associated with better prevention of gastric cancer, although not to a
      significant extent. No significant difference in incidence of gastric cancer was
      observed between patients with successful eradication therapy (32/2451 patients,
      1.31%) and those with treatment failure (11/639 patients, 1.72%). Among patients
      with duodenal ulcer, which is known to be more prevalent in younger individuals,
      the incidence of gastric cancer was significantly less in those with successful
      eradication therapy (2/845 patients, 0.24%) than in those with treatment failure
      (3/216 patients, 1.39%). CONCLUSION: H pylori eradication therapy for peptic
      ulcer patients with a mean age of 52.9 years at registration did not
      significantly decrease the incidence of gastric cancer.

PMID- 19750573
TI  - Small sphincterotomy combined with endoscopic papillary large balloon dilation
      versus sphincterotomy.
AB  - AIM: To compare small sphincterotomy combined with endoscopic papillary large
      balloon dilation (SES + ELBD) and endoscopic sphincterotomy (EST) for large bile
      duct stones. METHODS: We compared prospectively SES + ELBD (group A, n = 27) with
      conventional EST (group B, n = 28) for the treatment of large bile duct stones (>
      or = 15 mm). When the stone could not be removed with a normal basket, mechanical
      lithotripsy was performed. We compared the rates of complete stone removal with
      one session and application of mechanical lithotripsy. RESULTS: No significant
      differences were observed in the mean largest stone size (A: 20.8 mm, B: 21.3
      mm), bile duct diameter (A: 21.4 mm, B: 20.5 mm), number of stones (A: 2.2, B:
      2.3), or procedure time (A: 18 min, B: 19 min) between the two groups. The rates
      of complete stone removal with one session was 85% in group A and 86% in group B
      (P = 0.473). Mechanical lithotripsy was required for stone removal in nine of 27
      patients (33%) in group A and nine of 28 patients (32%, P = 0.527) in group B.
      CONCLUSION: SES + ELBD did not show significant benefits compared to conventional
      EST, especially for the removal of large (> or = 15 mm) bile duct stones.

PMID- 19750574
TI  - Prognostic analysis of patients with pancreatic head adenocarcinoma less than 2
      cm undergoing resection.
AB  - AIM: To investigate the differences in clinicopathological features between
      patients with pancreatic cancer greater or less than 2 cm situated over the
      pancreatic head and the prognostic factors for survival of patients with
      pancreatic cancer < 2 cm over the pancreatic head. METHODS: From 1983 to 2006,
      159 patients with histologically proven pancreatic adenocarcinoma (PAC) at the
      pancreatic head undergoing curative resection at the Department of Surgery, Chang
      Gung Memorial Hospital, Taipei, Taiwan were reviewed, comprising 123 cases of
      large (L)-PAC (tumor > 2 cm) and 36 cases of small (S)-PAC (tumor </= 2 cm). We
      compared the clinicopathological characteristics and prognosis of L-PAC and S-PAC
      patients. The clinicopathological characteristics of S-PAC were investigated to
      clarify the prognosis predictive factors of S-PAC. RESULTS: One hundred and fifty
      nine PAC patients, aged 16-93 years (median, 59.0 years) with a tumor at the
      pancreatic head undergoing intentional curative resection were investigated. The
      S-PAC and L-PAC patients had similar demographic data, clinical features, and
      tumor markers (a similar positive rate of carcinoembryonic antigen and
      carbohydrate antigen 19-9). There were also similar rates of lymph node
      metastasis, portal vein invasion, stage distribution, tumor differentiation,
      positive resection margin, surgical morbidity and mortality observed between the
      two groups. During a follow-up period ranging from 1.0 to 122.7 mo (median, 10.9
      mo), S-PAC and L-PAC patients had a similar prognosis after resection (P =
      0.4805). Among the S-PAC patients group, patients with higher albumin level (>
      3.5 g/dL) had more favorable survival than those with lower albumin levels, which
      was the only favorable predictive prognostic factor. Meanwhile, early-staged
      (stage I, II) S-PAC patients tended to have a more favorable outcome than late
      stage (stage III, IV) S-PAC patients, but this was not statistically significant.
      CONCLUSION: S-PAC patients should not be regarded as early PAC. Only higher
      albumin level (> 3.5 g/dL) and early stage disease (stage I, II) were the
      favorable prognosis factors for S-PAC patients.

PMID- 19750575
TI  - Baseline predictors of virological response for chronic hepatitis B patients.
AB  - AIM: To determine which baseline factors of chronic hepatitis B patients are
      predictive of virological response to Peginterferon alpha-2b therapy. METHODS: A
      total of 21 HBeAg-positive chronic hepatitis B (CHB) patients treated with
      Peginterferon alpha-2b were recruited. They were treated with Peginterferon alpha
      2b (0.5-1.0 microg/kg per week) for 24 wk and followed up for 24 wk. Clinical and
      laboratory data of the patients were determined at pretreatment and at week 12,
      at 24 during treatment, and at week 48 during follow up. RESULTS: Ten patients
      achieved a virological response at the end of treatment. Their baseline serum
      alanine aminotransferase (ALT), thyroid-stimulating hormone (TSH), and total
      thyroxin (TT4) levels were significantly different from those who failed
      treatment. The positive predictive values (PPV) and negative predictive values
      (NPV) of ALT, TSH, and TT4 were 75% and 89 %, 75% and 89 %, and 75% and 75%,
      respectively. Moreover, combinations of the baseline ALT and TT4, ALT and TSH,
      TT4 and TSH levels had much higher PPV and NPV (86% and 88%, 89% and 100%, 83%
      and 100%, respectively). CONCLUSION: Baseline serum ALT, TSH, and TT4 levels,
      especially in combination, have high predictive values of virological response to
      Peginterferon alpha-2b in HBeAg-positive CHB patients.

PMID- 19750576
TI  - Expression of thymidylate synthase and glutathione-s-transferase pi in patients
      with esophageal squamous cell carcinoma.
AB  - AIM: To investigate the expression of thymidylate synthase (TS) and glutathione-s
      transferase pi (GST-pi) in esophageal squamous cell carcinoma and their
      association with the clinicopathologic characteristics. METHODS:
      Immunohistochemical methods were used to detect the expression of TS and GST-pi
      in surgically resected formalin-fixed, paraffin-embedded esophageal squamous cell
      carcinoma (ESCC) tissue sections from 102 patients (median age, 58 years) and in
      28 normal esophageal mucosa (NEM) samples. The relationship between TS and GST-pi
      expression and clinicopathologic factors was examined. RESULTS: The expression of
      TS and GST-pi was not statistically significantly associated with age of the
      patients, tumor size, lymph node metastasis, depth of invasion or tumor stage. TS
      staining was positive in 17.86% of normal esophageal mucosa and in 42.16% of ESCC
      samples (P < 0.05). The expression level of TS was not only significantly lower
      in well-differentiated (21.88%) than in poorly-differentiated carcinomas (51.43%,
      P < 0.05), but was also significantly higher in samples from male patients
      (46.51%) than from female patients (18.75%, P < 0.05). GST-pi was positively
      stained in 78.57% of normal esophageal mucosa and in 53.92% of ESCC samples (P <
      0.05). The expression level of GST-pi was also significantly higher in well
      differentiated carcinomas (65.63%) than in poorly-differentiated carcinomas
      (35.00%, P < 0.05). CONCLUSION: The expression of TS and of GST-pi may be used as
      molecular markers for the characterization of ESCC. Poorly-differentiated cells
      showed increased expression of TS and reduced expression of GST-pi.

PMID- 19750577
TI  - Application of endoscopic hemoclips for nonvariceal bleeding in the upper
      gastrointestinal tract.
AB  - AIM: To investigate acute nonvariceal bleeding in the upper gastrointestinal (GI)
      tract and evaluate the effects of endoscopic hemoclipping. METHODS: Sixty-eight
      cases of acute nonvariceal bleeding in the upper GI tract were given endoscopic
      treatment with hemoclip application. Clinical data, endoscopic findings, and the
      effects of the therapy were evaluated. RESULTS: The 68 cases (male:female =
      42:26, age from 9 to 70 years, average 54.4) presented with hematemesis in 26
      cases (38.2%), melena in nine cases (13.3%), and both in 33 cases (48.5%). The
      causes of the bleeding included gastric ulcer (29 cases), duodenal ulcer (11
      cases), Dieulafoy's lesion (11 cases), Mallory-Weiss syndrome (six cases), post
      operative (three cases), post-polypectomy bleeding (five cases), and post
      sphincterotomy bleeding (three cases); 42 cases had active bleeding. The mean
      number of hemoclips applied was four. Permanent hemostasis was obtained by
      hemoclip application in 59 cases; 6 cases required emergent surgery (three cases
      had peptic ulcers, one had Dieulafoy's lesion, and two were caused by
      sphincterotomy); three patients died (two had Dieulafoy's lesion and one was
      caused by sphincterotomy); and one had recurrent bleeding with Dieulafoy's lesion
      10 mo later, but in a different location. CONCLUSION: Endoscopic hemoclip
      application was an effective and safe method for acute nonvariceal bleeding in
      the upper GI tract with satisfactory outcomes.

PMID- 19750578
TI  - Cytomegalovirus enteritis mimicking Crohn's disease in a lupus nephritis patient:
      a case report.
AB  - Cytomegalovirus (CMV) infection of the gastrointestinal (GI) tract has been
      reported in both immunocompetent and, more frequently, in immunocompromised
      patients. We describe a case of a 19-year-old male who developed CMV infection of
      the terminal ileum while receiving immunosuppression for lupus nephritis. This
      was a distinctly unusual site of infection which clinically mimicked Crohn's
      ileitis. We note that reports of terminal ileal CMV infection have been
      infrequent. Despite a complicated hospital course, ganciclovir therapy was
      effective in resolving his symptoms and normalizing his ileal mucosa. This report
      highlights the importance of accurate histological diagnosis and clinical follow
      up of lupus patients with GI symptoms undergoing intense immunosuppression.

PMID- 19750579
TI  - Rejection of Permacol mesh used in abdominal wall repair: a case report.
AB  - Permacol mesh has shown promise when used in abdominal wall repair, especially in
      the presence of a contaminated surgical field. This biomaterial, derived from
      porcine dermis collagen, has proposed advantages over synthetic materials due to
      increased biocompatibility and reduced foreign body reaction within human
      tissues. However, we present a case report describing a patient who displayed
      rejection to a Permacol mesh when used in the repair of abdominal wound
      dehiscence following an emergency laparotomy. Review of the English language
      literature using PubMed and Medline, showed only two previously published cases
      of explantation of Permacol due to sepsis or wound breakdown. The authors believe
      this is the first case of severe foreign body reaction leading to rejection of
      Permacol. Both animal and human studies show conflicting evidence of
      biocompatibility. There are several reports of successful use of Permacol to
      repair complex incisional herniae or abdominal walls in the presence of
      significant contamination. It appears from the literature that Permacol is a
      promising material, but as we have demonstrated, it has the potential to evoke a
      foreign body reaction and rejection in certain subjects.

PMID- 19750580
TI  - Resection of the uncinate process of the pancreas due to a ganglioneuroma.
AB  - A 33-year-old woman who presented with epigastric discomfort and diarrhea
      underwent an abdominal ultrasound (US). This investigation and subsequent
      contrast-enhanced computed tomography, magnetic resonance imaging and endoscopic
      US with fine needle aspiration (FNA) revealed a 40 mm well-circumscribed mass in
      the uncinate process of the pancreas. Findings were suggestive of a mucinous or
      solid-cystic pseudopapillary tumor of the pancreas, although other lesions such
      as a non-functioning neuroendocrine tumor could not be ruled out. FNA samples
      were negative for malignant cells, but of limited value due to poor cellularity.
      It was decided to surgically remove the tumor because malignancy could not be
      discounted. Multiple intraoperative biopsies were suggestive of mesenchymal tumor
      and consequently a conservative resection (uncinatectomy) was performed. The
      postoperative course was uneventful. The definitive diagnosis was ganglioneuroma.
      Immunocytochemistry showed positive staining with vimentin, S-100 protein,
      neurofilament and neuron-specific enolase. Ganglioneuroma is a rare benign tumor
      that can also present as a pancreatic tumor. Uncinatectomy is feasible, safe and
      a good surgical technique for the treatment of non-malignant tumors located in
      the uncinate process of the pancreas.

PMID- 19750581
TI  - Novel ABCB11 mutations in a Thai infant with progressive familial intrahepatic
      cholestasis.
AB  - Progressive familial intrahepatic cholestasis (PFIC) type 2 is caused by
      mutations in ABCB11, which encodes bile salt export pump (BSEP). We report a Thai
      female infant who presented with progressive cholestatic jaundice since 1 mo of
      age, with normal serum gamma-glutamyltransferase. Immunohistochemical staining of
      the liver did not demonstrate BSEP along the canaliculi, while multidrug
      resistance protein 3 was expressed adequately. Novel mutations in ABCB11, a four
      nucleotide deletion in exon 3, c.90_93delGAAA, and a single-nucleotide insertion
      in exon 5, c.249_250insT, were identified, with confirmation in her parents.
      These mutations were predicted to lead to synthesis of truncated forms of BSEP.
      Immunostaining and mutation analysis thus established the diagnosis of PFIC type
      2.

PMID- 19750582
TI  - Primary squamous cell carcinoma of pancreas diagnosed by EUS-FNA: a case report.
AB  - Squamous cell carcinoma of the pancreas has been sparsely described since the
      1940s, and generally has a poor prognosis. Herein, we present a case of primary
      squamous cell carcinoma of the pancreas with liver metastasis, both confirmed by
      endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). To the best of our
      knowledge, this is the first case report in literature utilizing EUS-FNA for a
      cell-type specific diagnosis of primary pancreatic squamous cell carcinoma with a
      liver metastasis.

PMID- 19750583
TI  - Biomarkers for noninvasive biochemical diagnosis of nonalcoholic steatohepatitis:
      tools or decorations?
AB  - In light of the growing epidemics of nonalcoholic fatty liver disease (NAFLD),
      identification and validation of the novel biochemical surrogate markers for
      nonalcoholic steatohepatitis (NASH) are paramount to reduce the necessity for
      liver biopsy. The availability of such markers has tremendous potential to
      radically alter the management strategies of NAFLD patients and to monitor the
      disease activity. Although current biomarkers do not entirely fulfill the many
      requirements for the identification of patients with NASH, they should not
      discourage our quest, but remind us that we need to cognize the challenges ahead.

PMID- 19750584
TI  - [Limbal relaxing incisions to correct preexisting astigmatism during  cataract
      surgery].
AB  - PURPOSE: To evaluate the effectiveness of limbal relaxing incisions for
      correcting significant preoperative astigmatism during cataract surgery. METHODS:
      In 32 patients (50 eyes) with preoperative keratometric astigmatism between 1.25
      and 2.5 D, cataract surgery was combined with limbal relaxing incisions according
      to a modified Gills nomogram. RESULTS: The mean preoperative keratometric
      astigmatism was 1.6 (+/- 0.39) D. The mean preoperative manifest refraction was
      1.26 ((+/- 0.39) D. The mean 1-month, 6-month and 3-year or more postoperative
      keratometric astigmatisms were 0.77 ((+/- 0.29), 0.84 ((+/- 0.5) and 0.86 ((+/-
      0.32) D, respectively. The mean postoperative manifest refractions were 0.48 ((+/
      0.32), 0.55 ((+/- 0.29) and 0.54 ((+/- 0.29) D, respectively. Postoperative
      refractive astigmatisms were 0 or 0.25 D in 22% of the cases, 0.5 or 0.75 D in
      64% and greater than 0.75 D in 14%. Conclusion.- Limbal relaxing incisions are an
      effective and simple approach to the correction of significant preoperative
      astigmatism during cataract surgery.

PMID- 19750585
TI  - [Current trends in the treatment of tinnitus].

PMID- 19750586
TI  - Antibiotic therapy for trachoma.
AB  - Trachoma, a major cause of blindness in some of the world's poorest countries,
      results from repeated or chronic eye infections with Chlamydia trachomatis.

PMID- 19750587
TI  - Interactive medical case. The writing on the wall.

PMID- 19750588
TI  - Editor's introduction. Violence against women with disabilities and deaf women.

PMID- 19750590
TI  - [2nd Hyperlipoproteinemia congress in Serbia with international participation.
      Novi Sad, 17-19 September 2008].

PMID- 19750589
TI  - Immunotherapy with dendritic cells pulsed by autologous dactinomycin-induced
      melanoma apoptotic bodies for patients with malignant melanoma.
AB  - The primary goal of this study was to evaluate the efficacy of immunotherapy for
      patients with metastatic melanoma with autologous melanoma apoptotic bodies (MAB)
      pulsed dendritic cells (DCs). Accessible tumors from eligible patients with
      refractory metastatic melanoma were surgically removed and processed for primary
      culture. The autologous tumor cells were treated with dactinomycin to obtain MAB.
      To generate DCs, adherent peripheral blood mononuclear cells were cultured in
      complete medium containing granulocyte macrophage-colony stimulating factor and
      interleukin-4. MAB-pulsed DCs were given either intradermally (i.d.) or
      intravenously. Patients were immunized at monthly intervals and boosted with
      keyhole limpet hemocyanin (KLH) and MAB 2 weeks post-vaccination, with a maximum
      of four cycles. Of the 10 patients enrolled in this trial, nine were treated with
      MAB-pulsed DCs; two were given intravenous vaccinations and the other seven were
      i.d. injected. Mild tenderness in the draining lymph nodes lasting for less than
      48 h and enlargement of the draining lymph nodes were noted in all seven i.d.
      cases. Treatment-related grade 3-4 toxicity, neutropenia, skin ulceration, tumor
      growth at the injection site, and sepsis were not observed in any of the
      patients. Delayed-type hypersensitivity to KLH was observed in all patients,
      whereas no delayed-type hypersensitivity to autologous tumor antigens was
      observed. One patient achieved partial response with reduction in lung metastatic
      tumor mass, and a presence of vesicles in the post-vaccination KLH response. Two
      patients had stable disease for more than 24 months; one was still alive at the
      time of submission of this report, the other eventually developed multiple
      metastases. MAB-pulsed DC immunotherapy is well tolerated in patients with
      malignant melanoma; however, its efficacy is only modest. Combination with other
      modalities is required to enhance DC-based immunotherapy.

PMID- 19750591
TI  - Preface. Effects of Climate Change on Plants: Implications for Agriculture.

PMID- 19750592
TI  - [Orbital metastasis from cutaneous melanoma].
AB  - PURPOSE: We report the case of a patient presenting with a one-sided orbital
      metastasis from a cutaneous melanoma, and analyze clinical features, diagnostic
      difficulties and prognosis of such metastasis. CASE REPORT: We report the case of
      a woman aged 70 years, who presented with a right one-sided proptosis associated
      to a decrease of the vision. The clinical features were: visual acuity at 2/10,
      an axile proptosis and a papillary sectorial temporal atrophy. The computed
      tomography (CT) disclosed an intraorbital mass with double tonality, rounded and
      well limited driving back the optic nerve and erasing the limits of the lateral
      rectus muscle. The orbital magnetic resonance imaging (MRI) showed an intra-conal
      fusiform mass with an heterogeneous signal in T1 and T2, heightening intensely
      and heterogeneously after the injection of Gadolinium. Otherwise, the patient
      presented with an associated respiratory failure, and thoracic CT has disclosed
      diffuse metastases. It was then noted that a cutaneous melanoma of the left foot
      had been operated ten years before. The patient died during the following month.
      DISCUSSION: The cutaneous melanoma is a rare cause of orbital metastasis. The
      diagnosis is often easy, when a primitive tumor is known, but it remains
      uncertain for a long time. CONCLUSION: Orbital metastases from cutaneous melanoma
      are rare, generally occurring at the late stage of the disease with a life
      expectancy not passing one year.

PMID- 19750593
TI  - Eyeing the underdog.
AB  - Can Philadelphia's biotechnology industry absorb the jobs lost from
      pharmaceutical companies? Kerry Grens investigates.

PMID- 19750594
TI  - The best way.

PMID- 19750595
TI  - Modeling and numerical study of the  electroacoustic behavior in integrated 
      piezoelectric structures under external  mechanical stress.
AB  - The purpose of this study is to model and understand the role of an applied
      mechanical stress in piezoelectric materials as far as electroacoustic parameters
      are concerned.In the field of thick or thin film technology, understanding and
      predicting the behavior of integrated structures when submitted to external or
      internal mechanical stress is of primary importance. Thus, we propose a modified
      KLM electroacoustic model of transducer that enables to take into account the
      effect of a mechanical pre-stress. Then, a numerical study of the electroacoustic
      parameters for lithium niobate piezoelectric material(coupling coefficient,
      velocities, associated polarizations,and electrical input impedance) is conducted
      with regard to the azimuthal and elevation angles, as well as initial pre-stress
      values. Finally, we study the pulse-echo response of a complete piezoelectric
      transducer consisting of a piezoelectric film laid down upon a backing material
      and matching layers, with and without an initial stress, to highlight some
      benefits of a prestress load.

PMID- 19750596
TI  - Quantitative ultrasound backscatter for  pulsed cavitational ultrasound therapy- 
      histotripsy.
AB  - Histotripsy is a well-controlled ultrasonic tissue ablation technology that
      mechanically and progressively fractionates tissue structures using cavitation.
      The fractionated tissue volume can be monitored with ultrasound imaging because a
      significant ultrasound backscatter reduction occurs.This paper correlates the
      ultrasound backscatter reduction with the degree of tissue fractionation
      characterized by the percentage of remaining normal-appearing cell nuclei on
      histology.Different degrees of tissue fractionation were generated in vitro in
      freshly excised porcine kidneys by varying the number of therapeutic ultrasound
      pulses from 100 to 2000 pulses per treatment location. All ultrasound pulses were
      15 cycles at 1 MHz delivered at 100 Hz pulse repetition frequency and 19 MPa peak
      negative pressure. The results showed that the normalized backscatter intensity
      decreased exponentially with increasing number of pulses. Correspondingly, the
      percentage of normal appearing nuclei in the treated area decreased exponentially
      as well. A linear correlation existed between the normalized backscatter
      intensity and the percentage of normal appearing cell nuclei in the treated
      region. This suggests that the normalized backscatter intensity may be a
      potential quantitative real-time feedback parameter for histotripsy-induced
      tissue fractionation. This quantitative feedback may allow the prediction of
      local clinical outcomes, i.e., when a tissue volume has been sufficiently
      treated.

PMID- 19750597
TI  - Science on the move: recent trends in the history of Early Modern science.

PMID- 19750598
TI  - "A pattern, precedent, and lively warrant": emulation, rhetoric, and cruel
      propriety in "Titus Andronicus.".
AB  - Shakespeare's "Titus Andronicus" critically engages and enacts teachings and
      patterns of emulation, including those of Quintilian, Roger Ascham, and other
      contemporary humanists and playwrights, pressing emulation's uses to extremes
      that suggest that imitative self-fashioning potentially results in monstrous or
      fragmented characters, decisions, and texts. The professed aim of the grammer
      school education, the ability to judge well, is conflicted by "Titus's" exposure
      of judgment as itself a contested concept, locked within a circularity of
      intertextual precedents. "Titus's" excessive, even parodic, repetition of
      emulative strategies acts as a rebuttal of seemingly straightforward humanist
      models of character, judgment, self, and decorum.

PMID- 19750599
TI  - "Perplex't paths": youth and authority in Milton's Mask.
AB  - This essay argues that John Milton's "A Mask Presented at Ludlow Castle" (1634)
      is influenced by early modern concepts of childhood in a way that critics have
      not recognized. Childhood was a problematic concept in contemporary religious,
      pedagogical, and legal discourses. Children were depicted as models of
      submission, but prone to impetuous indiscretion, and their path to adult agency
      was strewn with pitfalls, especially in the liminal period of youth. "A Mask"
      engages with and transforms these discourses. It rejects the political quietism
      routinely associated with childhood and shows that the child's unique sensitivity
      may offer a route to a particularly powerful kind of voice.

PMID- 19750600
TI  - Time to declare E&M codes dead.

PMID- 19750601
TI  - For reasons of state: political executions, republicanism, and the Medici in
      Florence, 1480-1560.

PMID- 19750602
TI  - "Do not eat those apples; they've been on the ground!": polio epidemics and
      preventive measures, Sweden 1880s-1940s.
AB  - This article will address how Swedish scientists, physicians and public health
      officers tried to combat the polio epidemics in the pre-vaccine era. It shows
      that once polio was considered as an epidemic disease the preventive measures
      used were based on the hindrance of other infectious diseases. It also
      illustrates how epidemiological and laboratory studies to some degree affected
      the thoughts of how polio should be prevented, and that Swedish ideas and
      experiences differed from those put forward in the USA.

PMID- 19750603
TI  - [Description of a trichinosis outbreak in the province of Salamanca].

PMID- 19750604
TI  - [Do bone marrow cells introduce arrhythmia?].

PMID- 19750605
TI  - [Desmin as predictor of survival in patients with chronic heart failure].

PMID- 19750606
TI  - [Do need registry - diagnosis and therapy of acute pulmonary embolism].

PMID- 19750607
TI  - The 'Whats' and the 'hows' of general practitioner learning.

PMID- 19750608
TI  - [Electrocardiography for risk assessment of patients with pulmonary embolism].

PMID- 19750609
TI  - [Postoperative complications during percutaneous coronary interventions- one more
      risk factor?].

PMID- 19750610
TI  - [Epidemiological and virological studies into the poliomyelitis in Valencia (1959
      1969)].
AB  - Studies into the polio virus began in Valencia in 1959 with the work undertaken
      by the microbiologist Vicente Sanchis-Bayarri Vaillant. After his education at
      the Rochester University and at the Pasteur Institute, Sanchis-Bayarri Vaillant
      established a laboratory of cell cultures at the Faculty of Medicine in Valencia,
      where he developed a new diagnostic technique for the poliomyelitis virus. In
      addition, epidemiological studies were carried out both prior to and post the
      1963 vaccination campaign, which proved that Sabin's oral vaccine was both
      effective and safe for use.

PMID- 19750611
TI  - Canadian recommendations for the prevention and treatment of malaria among
      international travellers--2009.

PMID- 19750612
TI  - [The historical meaning of serological surveys as a laboratory technology applied
      to the immunization campaigns. The case of poliomyelitis in Spain].
AB  - The aim of the paper is to analyse the introduction, use and diffusion of the
      serological surveys, a public health technology on the borderline between
      epidemiology and laboratory, in connection with poliomyelitis in Spain during the
      Francoism period. Within the framework of the "new history" of medical
      technologies and innovations, the serological surveys played an important role
      both in the improvement of knowledge on socio-demographic distribution and the
      health politics arena.

PMID- 19750613
TI  - Rigid lipid membranes and nanometer clefts: motifs for the creation of molecular
      landscapes.
AB  - Amphiphilic lipids associate in water spontaneously to form micelles, vesicles,
      monolayers, or biological membranes. These aggregates are soft and their shape
      can be changed easily. They behave like complex fluids because they are merely
      held together by weak, nondirected forces. The most important characteristic of
      these monolayers is their ability to dissolve hydrophobic molecules in the form
      of freely movable monomers. The fluid molecular layers are not suitable to anchor
      the components of chain reactions. However, if the alkyl chains are replaced by
      rigid skeletons or if the head groups are connected through intermolecular
      interactions, the aggregates become rigid and their fluid solvent character is
      lost. The construction of chiral surfaces by synkinesis (synthesis of noncovalent
      compounds) and of enzyme-type surface clefts of defined size can now be carried
      out by using rigid lipid membranes. Monolayers and nanometer pores on solid
      substrates attain sharp edges, and upright nanometer columns on smooth surfaces
      no longer dissipate. Five examples illustrate the advantages of using rigid
      molecular assemblies: 1) Cationic domains of rigid edge amphiphiles in fluid
      membranes act as manipulable ion channels. 2) Spherical micelles, micellar
      helical fibers, and vesicular tubes can be dried and stored as stable material.
      Molecular landscapes form on smooth surfaces. 3) alpha,omega-Diamide
      bolaamphiphiles form rigid nanometer-thick walls on smooth surfaces and these
      barriers cannot be penetrated by amines. Around steroids and porphyrins, they
      form rigid nanometer clefts whose walls and water-filled centers can be
      functionalized. 4) The structure of rigid oligophenylene- and quinone monolayers
      on electrodes can be changed drastically and reversibly by changing the
      potential. 5) 10(10) Porphyrin cones on a 1-cm2 gold electrode can be controlled
      individually by AFM- and STM-tips and investigated by electrochemical,
      photochemical, and mechanical means. In summary, rigid monolayers and bilayers
      allow the formation of a great variety of membrane structures that cannot be
      obtained from classical fluid alkyl amphiphiles.

PMID- 19750614
TI  - Functionalization of single-walled carbon nanotubes.
AB  - Through chemical functionalization of single-walled carbon nanotubes, the
      prerequisites for possible applications of such nanostructures are established.
      The derivatized tubes differ from the crude materials in their good solubility,
      which enables both a more extensive characterization and subsequent chemical
      reactivity. Current derivatization methods include defect and covalent sidewall
      functionalization, as well as noncovalent exo- and endohedral functionalization.
      In this way, for example, a range of nanotubes can be prepared: with sidewall
      substituents, wrapped with polymers, or with guest molecules included. The
      current state of the literature is presented in this Minireview.

PMID- 19750615
TI  - A spiropentasiladiene and other strained silicon-containing rings.

PMID- 19750616
TI  - Microwave-assisted reactions in organic synthesis--are there any nonthermal
      microwave effects?

PMID- 19750617
TI  - Biosynthesis of polyunsaturated fatty acids by polyketide synthases.

PMID- 19750618
TI  - Sp carbon chains surrounded by sp3 carbon double helices: a class of molecules
      that are accessible by self-assembly and models for "insulated" molecular-scale
      devices.

PMID- 19750619
TI  - Cis-trans selectivity of enzyme-catalyzed additions to 4-substituted
      cyclohexanones--correlation with the Prelog/Ringold model of enzymatic
      hydrogenation.

PMID- 19750620
TI  - Selective alpha-carbon hydroxylation of glycine in nickel(II)-cyclotetrapeptide
      complexes by oxygen.

PMID- 19750621
TI  - [Ga22{N(SiMe3)2}10]2-: a metalloid cluster compound with a variation of the Ga22
      framework.

PMID- 19750622
TI  - The catalytic use of onion-like carbon materials for styrene synthesis by
      oxidative dehydrogenation of ethylbenzene.

PMID- 19750623
TI  - Tin analogues of "Arduengo carbenes": synthesis of 1,3,2lambda2-diazastannoles
      and transfer of Sn atoms between a 1,3,2lambda2-diazastannole and a diazadiene.

PMID- 19750624
TI  - Stable helical secondary structure in short-chain N,N'-linked oligoureas bearing
      proteinogenic side chains.

PMID- 19750625
TI  - Self-assembling organic nanotubes from enantiopure cyclo-N,N'-linked oligoureas:
      design, synthesis, and crystal structure.

PMID- 19750626
TI  - Drastic luminescence response to carbon monoxide from a RuII complex containing a
      hemilabile phosphane pyrene ether.

PMID- 19750627
TI  - Shape-persistent, fluorescent polyphenylene dyads and a triad for efficient
      vectorial transduction of excitation energy.

PMID- 19750628
TI  - Enantiomeric self-recognition of a facial amphiphile triggered by
      [{Pd(ONO2)(en)}2].

PMID- 19750629
TI  - Crystal engineering of mixed-metal Ru-Ag coordination networks by using the trans
      [RuCl2(pyz)4] (pyz = pyrazine) building block.

PMID- 19750630
TI  - Synthesis of metal nanoparticles by using polyoxometalates as photocatalysts and
      stabilizers.

PMID- 19750631
TI  - Light-controlled nitric oxide generation from a novel self-assembled monolayer on
      a gold surface.

PMID- 19750632
TI  - Complete stereospecific cyclopropanation of alpha,beta-unsaturated amides
      promoted by Sm/CH2I2.

PMID- 19750633
TI  - The amide protons of an ytterbium(III) dota tetraamide complex act as efficient
      antennae for transfer of magnetization to bulk water.

PMID- 19750634
TI  - Crystal structure of K2[C2O6]--first proof of existence and constitution of a
      peroxodicarbonate ion.

PMID- 19750635
TI  - Self-assembled receptors for enantioselective recognition of chiral carboxylic
      acids in a highly cooperative manner.

PMID- 19750636
TI  - Designed ligands as probes for the catalytic binding mode in Mo-catalyzed
      asymmetric allylic alkylation.

PMID- 19750637
TI  - Creation of a unique self-supported pattern of radially aligned semiconductor
      Ag2S nanorods.

PMID- 19750638
TI  - Total synthesis of (-)-strychnine.

PMID- 19750639
TI  - Stereocontrolled synthesis of the quinaldic acid macrocyclic system of
      thiostrepton.

PMID- 19750640
TI  - A biomimetically inspired synthesis of the dehydropiperidine domain of
      thiostrepton.

PMID- 19750641
TI  - Method for palladium-catalyzed cross-couplings of simple alkyl chlorides: Suzuki
      reactions catalyzed by [Pd2(dba)3]/PCy3.

PMID- 19750642
TI  - Hydrogen bonding modulates the selectivity of enzymatic oxidation by P450:
      chameleon oxidant behavior by compound I.

PMID- 19750643
TI  - A dynamic rearrangement of a metal cluster in a process that closely resembles
      the hopping mechanism of adatom diffusion on metal surfaces.

PMID- 19750644
TI  - Electronic structure and bonding in hexacoordinate silyl-palladium complexes.

PMID- 19750645
TI  - Hexakis(silyl)palladium(VI) or palladium(II with eta2-disilane ligands?.

PMID- 19750646
TI  - A 3D open-framework indium telluride and its selenide and sulfide analogues.

PMID- 19750647
TI  - Structural transitions in clusters.
AB  - If one adds more particles to a cluster, the energetically optimal structure is
      neither preserved nor does it change in a continuous fashion. Instead, one finds
      several cluster size regions where one structural principle dominates almost
      without exception, and rather narrow boundary regions in-between. The structure
      of the solid is usually reached only at relatively large sizes, after more than
      one structural transition. The occurrence of this general phenomenon of size
      dependent structural transitions does not seem to depend on the nature of the
      particles, it is found for atomic, molecular, homogeneous, and heterogeneous
      clusters alike. Clearly, it is a collective many-body phenomenon which can in
      principle be calculated but not understood in a fully reductionistic manner.
      Actual calculations with sufficient accuracy are not feasible today, because of
      the enormous computational expense, even when unconventional evolutionary
      algorithms are employed for global geometry optimization. Therefore, simple rules
      for cluster structures are highly desirable. In fact, we are dealing here not
      just with the academic quest for linkages between cluster structure and features
      of the potential energy surface, but structural transitions in clusters are also
      of immediate relevance for many natural and industrial processes, ranging from
      crystal growth all the way to nanotechnology. This article provides an exemplary
      overview of research on this topic, from simple model systems where first
      qualitative explanations start to be successful, up to more realistic complex
      systems which are still beyond our understanding.

PMID- 19750648
TI  - Molecular encapsulation.
AB  - Louis Kahn, architect of the Salk Institute in LaJolla, said "even a common,
      ordinary brick wants to be something more than it is". Suppose that were also
      true of molecules. We know that they can and do aggregate; they give complex
      structures, and by doing so they acquire new properties--functions that may not
      be apparent from a study of the individual components. This review is about
      molecular aggregates of a certain sort, namely, those that assemble and more or
      less completely surround other molecules. Taking part in this intimacy imparts
      unique properties to the participants, and new functions emerge from the
      aggregate as a whole. For the most part, we emphasize self-complementary
      structures. Their ability to assemble-an expression of the molecule's desire to
      be something more than it is--results from instructions engineered into the
      molecules during their creation.

PMID- 19750649
TI  - Protein-inspired materials: synthetic concepts and potential applications.

PMID- 19750650
TI  - Of molecular gyroscopes, matroshka dolls, and other "nano"-toys.

PMID- 19750651
TI  - Direct observation of radicals in the activation of Ziegler-Natta catalysts.

PMID- 19750652
TI  - Combinatorial libraries with P-functionalized aminopyridines: ligands for the
      preparation of efficient C(aryl)-Cl activation catalysts.

PMID- 19750653
TI  - Facile construction of the colchicine skeleton by a rhodium-catalyzed
      cyclization/cycloaddition cascade.

PMID- 19750654
TI  - Aromatic boranes with planar-tetracoordinate boron atoms and very short B--B
      distances.

PMID- 19750655
TI  - A planar, aromatic bicyclo-tetraborane(4).

PMID- 19750656
TI  - Synthesis of enantioenriched 5-alkylidene-2-cyclopentenones from chiral allenyl
      carbamates: generation of a chiral lithium allenolate and allylic activation for
      a conrotatory 4pi-electrocyclization.

PMID- 19750657
TI  - Near-UV photoionization of [Ru(bpy)3]2+: a catalytic cycle with an excited
      species as catalyst.

PMID- 19750658
TI  - Characterization and photochemistry of the silane-aluminum complex Al.SiH4 and
      its photoproducts HAlSiH3 and AlSiH3 in a solid argon matrix.

PMID- 19750659
TI  - Mesophases of (bio)polymer-silica particles inspire a model for silica
      biomineralization in diatoms.

PMID- 19750660
TI  - The mechanical properties of human angiostatin can be modulated by means of its
      disulfide bonds: a single-molecule force-spectroscopy study.

PMID- 19750661
TI  - Colorimetric and fluorometric detection of nucleic acids using cationic
      polythiophene derivatives.

PMID- 19750662
TI  - Conformationally flexible, chiral quaternary ammonium bromides for asymmetric
      phase-transfer catalysis.

PMID- 19750663
TI  - A model system mimicking glycosphingolipid clusters to quantify carbohydrate self
      interactions by surface plasmon resonance.

PMID- 19750664
TI  - Paratropic delocalized ring currents in flattened cyclooctatetraene systems with
      bond alternation.

PMID- 19750665
TI  - A three-dimensional homometallic molecular ferrimagnet.

PMID- 19750666
TI  - Arene-perfluoroarene interactions as physical cross-links for hydrogel formation.

PMID- 19750667
TI  - Hybrid molecular dumbbells: bridging polyoxometalate clusters with an organic pi
      conjugated rod.

PMID- 19750668
TI  - Concise total synthesis of (-)-frondosin B using a novel palladium-catalyzed
      cyclization.

PMID- 19750669
TI  - Mechanism and origin of stereoselectivity in Lewis acid catalyzed [2 + 2]
      cycloadditions of ketenes with aldehydes.

PMID- 19750670
TI  - Cyclotetrasilenide ion: a reversible redox system of cyclotetrasilenyl cation,
      radical, and anion.

PMID- 19750671
TI  - Ortho substituents direct regioselective addition of tributyltin hydride to
      unsymmetrical diaryl (or heteroaryl) alkynes: an efficient route to stannylated
      stilbene derivatives.

PMID- 19750672
TI  - Evaluation of Diene hierarchies for Diels--Alder reactions en route to
      xestocyclamine A: elaboration of an Ansa bridge by B-alkyl Suzuki
      macrocyclization.

PMID- 19750673
TI  - Synthesis of alpha-methylene-gamma-butyrolactones: Ru-catalyzed
      cyclocarbonylation of allenyl aldehydes and allenyl ketones.

PMID- 19750674
TI  - Novel ene-like cycloisomerization reaction of nitrile oxides with a tethered
      allyltrimethylsilyl group.

PMID- 19750675
TI  - A triple-decker complex with a central metallabenzene.

PMID- 19750676
TI  - Synthesis, structure, and molecular orbital calculations of chromium(III) and
      iron(III) complexes containing eta2-pyrazolato ligands.

PMID- 19750677
TI  - Hexagonal and cubic thermally stable mesoporous tin(IV) phosphates with acidic
      and catalytic properties.

PMID- 19750678
TI  - The first isolable 1,1-dilithiogermane and its unusual dimeric structure--an
      effective reagent for the preparation of double-bonded derivatives of group 14
      elements.

PMID- 19750679
TI  - Stereoselective synthesis of Boc-protected cis and trans-4
      trifluoromethylprolines by asymmetric hydrogenation reactions.

PMID- 19750680
TI  - In situ enzymatic screening (ISES): a tool for catalyst discovery and reaction
      development.

PMID- 19750681
TI  - A novel rhodium-catalyzed reduction-oxidation process: reaction of 4-alkynals
      with phenol to provide cis-4-alkenoates.

PMID- 19750682
TI  - General preparation of functionalized o-nitroarylmagnesium halides through an
      iodine-magnesium exchange.

PMID- 19750683
TI  - A chiral 1,2-bisphospholane ligand with a novel structural motif: applications in
      highly enantioselective Rh-catalyzed hydrogenations.

PMID- 19750684
TI  - Helical chiral polymers without additional stereogenic units: a new class of
      ligands in asymmetric catalysis.

PMID- 19750685
TI  - Catalytic enantioselective Diels--Alder reactions: methods, mechanistic
      fundamentals, pathways, and applications.
AB  - One hundred years after the birth of Kurt Alder and seventy-five years after the
      discovery of his famous reaction, one of the most important and fascinating
      transformations in chemistry, research on that process continues to surprise,
      excite, delight, and inform the chemical community. This article is based on
      presentations given first at the University of Cologne, Germany (Kurt Alder
      lecture, 1992), then at the Roger Adams Award Symposium (1993), and later at the
      Burgenstock Conference of 2001, and describes research by our group on the
      development and understanding of enantioselective versions of the Diels-Alder
      reactions. The elements of this review include (1) development of new chiral
      Lewis acid catalysts for highly enantioselective (>25:1) [4+2] cycloadditions;
      (2) the fine mechanistic details and pre-transition-state assemblies of these
      reactions; (3) the fundamental understanding of catalytic activity and
      enantioselectivity for highly enantioselective Diels-Alder processes; and (4)
      applications to the synthesis of complex molecules. The range and power of the
      Diels-Alder reaction have steadily increased over seven decades. The end of this
      remarkable development is not in sight, a high compliment to this field of
      Science and to its great inventor.

PMID- 19750686
TI  - The Diels--Alder reaction in total synthesis.
AB  - The Diels-Alder reaction has both enabled and shaped the art and science of total
      synthesis over the last few decades to an extent which, arguably, has yet to be
      eclipsed by any other transformation in the current synthetic repertoire. With
      myriad applications of this magnificent pericyclic reaction, often as a crucial
      element in elegant and programmed cascade sequences facilitating complex molecule
      construction, the Diels-Alder cycloaddition has afforded numerous and
      unparalleled solutions to a diverse range of synthetic puzzles provided by nature
      in the form of natural products. In celebration of the 100th anniversary of
      Alder's birth, selected examples of the awesome power of the reaction he helped
      to discover are discussed in this review in the context of total synthesis to
      illustrate its overall versatility and underscore its vast potential which has
      yet to be fully realized.

PMID- 19750687
TI  - How attractive is bromine as a protecting group in aromatic chemistry?

PMID- 19750688
TI  - Na3N--an original synthetic route for a long sought after binary nitride.

PMID- 19750689
TI  - Oligomerization of p53 upon cooperative DNA binding: towards a structural
      understanding of p53 function.

PMID- 19750690
TI  - Semiconductor nanohelices templated by supramolecular ribbons.

PMID- 19750691
TI  - Assignment of stereochemistry of facially protected bis-porphyrins by use of a
      "Molecular ruler".

PMID- 19750692
TI  - A four-step alternating reductive dimerization/bond cleavage of
      indenocorannulene.

PMID- 19750693
TI  - Per(6-amino-2-O-carboxymethyl-6-deoxy-3-O-methyl)-alpha-cyclodextrin: helical
      self-assembly of a polyionic amino acid into nanotubes.

PMID- 19750694
TI  - cis-2-aminocyclopentanecarboxylic acid oligomers adopt a sheetlike structure:
      switch from helix to nonpolar strand.

PMID- 19750695
TI  - Chiral transmission between amino acids: chirally selective amino acid
      substitution in the serine octamer as a possible step in homochirogenesis.

PMID- 19750696
TI  - Hydrogen-bonded helices in crystals with prescribed organization.

PMID- 19750697
TI  - A one-pot synthesis of chromophoric silicate-based xerogels.

PMID- 19750698
TI  - Silicon--enamine complexes: pentacoordinate silicon compounds.

PMID- 19750699
TI  - The adsorption of cyclopropane and cyclohexane on Cu(111): an experimental and
      theoretical investigation on the nature of the CH-metal interaction.

PMID- 19750700
TI  - Pentaphosphaferrocene as a linking unit for the formation of one- and two
      dimensional polymers.

PMID- 19750701
TI  - Structure and synthesis of the natural heptachloro-1'-methyl-1,2'-bipyrrole (Q1).

PMID- 19750702
TI  - An efficient nucleophilic carbene catalyst for the asymmetric benzoin
      condensation.

PMID- 19750703
TI  - New catalyst systems for the catalytic conversion of methane into methanol.

PMID- 19750704
TI  - Synthesis of the protein phosphatase 2A inhibitor (4S,5S,6S,10S,11S,12S)
      cytostatin.

PMID- 19750705
TI  - Modular building blocks for amino acid recognition in peptides.

PMID- 19750706
TI  - Synthesis and structure of Na3N.

PMID- 19750707
TI  - Synthesis of a strapped calix[4]pyrrole: structure and anion binding properties.

PMID- 19750708
TI  - Profound steric control of reactivity in aryl halide addition to bisphosphane
      palladium(0) complexes.

PMID- 19750709
TI  - Weak distance dependence of excess electron transfer in DNA.

PMID- 19750710
TI  - A highly specific Ca2+ -ion sensor: signaling by exciton interaction in a rigid
      flexible-rigid bichromophoric "H" foldamer.

PMID- 19750711
TI  - Unidirectional photoinduced shuttling in a rotaxane with a symmetric stilbene
      dumbbell.

PMID- 19750712
TI  - Samarium diiodide-induced reductive cross-coupling of nitrones with aldehydes and
      ketones.

PMID- 19750713
TI  - Oxidative cyclization-dimerization reaction of 2,3-allenoic acids and 1,2-allenyl
      ketones: an efficient synthesis of 4-(3'-furanyl)butenolide derivatives.

PMID- 19750714
TI  - Enantiospecific synthesis of the bridged pyrrolizidine core of asparagamine A:
      dipolar cycloadditions of azomethine ylides derived from the sulfonylation of
      vinylogous amides.

PMID- 19750715
TI  - Cyanamide synthesis by the palladium-catalyzed cleavage of a Si-N bond.

PMID- 19750716
TI  - A short synthesis of (+/-)-13-deoxyserratine.

PMID- 19750717
TI  - Synthesis and characterization of a digermanium analogue of an alkyne.

PMID- 19750718
TI  - A cascade cycloaddition strategy leading to the total synthesis of (-)-FR182877.

PMID- 19750719
TI  - Direct organo-catalytic asymmetric alpha-amination of aldehydes--a simple
      approach to optically active alpha-amino aldehydes, alpha-amino alcohols, and
      alpha-amino acids.

PMID- 19750720
TI  - A new trend in phenalenyl chemistry: A persistent neutral radical, 2,5,8-tri-tert
      butyl-1,3-diazaphenalenyl, and the excited triplet state of the gable syn-dimer
      in the crystal of column motif.

PMID- 19750721
TI  - Expanding the reaction scope of DNA-templated synthesis.

PMID- 19750722
TI  - Response to managed care.

PMID- 19750723
TI  - Response to managed care.

PMID- 19750724
TI  - Facing the standard of care of a new millennium.

PMID- 19750725
TI  - The use of a self-aligning, low-maintenance overdenture attachment.

PMID- 19750726
TI  - Cavities may soon be a thing of the past.

PMID- 19750727
TI  - Cultural understanding fostered through company program.

PMID- 19750728
TI  - A comparison of at-home and in-office bleaching.

PMID- 19750729
TI  - Combining bonded and cemented restorations: a multitechnique case study.

PMID- 19750730
TI  - The 3-hour cosmetic rehabilitation.

PMID- 19750731
TI  - Maxillary ridge augmentation using mandibular symphysis graft.

PMID- 19750732
TI  - Update on anterior restorative materials: an interview with Dr. Dan Nathanson.
      Interview by Phillip Bonner.

PMID- 19750733
TI  - An evidence-based review of posterior single-tooth replacement: implants vs fixed
      partial dentures.

PMID- 19750734
TI  - Oral sedation for the apprehensive dental patient.

PMID- 19750735
TI  - Dental software: what's hot, what's not, what's next.

PMID- 19750736
TI  - Closing the gap: educating patients on aesthetic restorative treatments.

PMID- 19750737
TI  - NIDCR looks to the future. Interview by Phillip Bonner.

PMID- 19750738
TI  - Viewing hygiene as a business within the business, part 3.

PMID- 19750739
TI  - The super practice: a marketing and professionalism hybrid.
AB  - The old standard dental practice of yesterday, with a stubborn dentist who thinks
      marketing and advertising (concepts key to retail establishment success) are
      "unethical" doesn't cut it anymore. The practical retail concepts discussed about
      in this article allow dentists to create a marketing and professionalism hybrid.
      Providing first-class, customer-service treatment is the underlying principle.
      Patients who feel their dentist and staff know them will always feel at ease and
      a great sense of loyalty. The reward for treating patients like customers,
      consumers, and friends is that patients patronize businesses, including dental
      practices that meet or exceed their expectations. There's a man driving down your
      street right now with a toothache. Will it be your practice or the one down the
      block.

PMID- 19750740
TI  - Buyers' guide to intraoral cameras and imaging. Technology for the new
      millennium: intraoral cameras and cosmetic imaging systems.

PMID- 19750741
TI  - Dietary trial using a commercial hypoallergenic diet containing hydrolyzed
      protein for dogs with inflammatory bowel disease.
AB  - Six dogs with inflammatory bowel disease (IBD) received a commercially available
      hypoallergenic diet containing an enzymatically hydrolyzed defatted soy globulin
      as the only protein source. Five of the six dogs had been refractory to a variety
      of controlled diets, and four dogs had failed to respond to previous medical
      therapy. All dogs were fed the test diet twice daily for 10 weeks. Dogs not
      showing adequate improvement in clinical signs after 2 to 4 weeks on diet alone
      had appropriate medical therapy added to the dietary regimen. Gastroduodenoscopy
      and biopsy were performed on Day 0 and repeated at the conclusion of the study.
      Intestinal biopsies were evaluated by a pathologist using a numeric grading
      scheme to describe histologic alterations and mucosal architecture. Dietary
      therapy alone provided adequate clinical improvement in four dogs, and concurrent
      medical therapy was required in two dogs, one of which had exocrine pancreatic
      insufficiency. Mean fecal scores improved after therapy. Five dogs showed mild to
      moderate histologic improvement in duodenal biopsies after therapy. The clinical
      improvement observed cannot be solely attributed to the hydrolyzed nature of the
      protein source because the diet tested was highly digestible, contained
      cornstarch (rather than intact grains) and a source of medium-chain triglycerides
      (23% of fat), and had an altered ratio of omega-6 to omega-3 polyunsaturated
      fatty acids. Nevertheless, the resolution of clinical signs and improved biopsy
      scores demonstrate the importance of conducting further studies to critically
      assess the role of diets containing a hydrolyzed protein source for the
      management of dogs with previously refractory IBD.

PMID- 19750742
TI  - Neutralizing antibody responses in preconditioned calves following vaccination
      for respiratory viruses.
AB  - Calf preconditioning programs that include vaccinations against common
      respiratory pathogens are beneficial; however, optimal vaccination protocols have
      not been determined. In the study described here, calves were placed in a
      preconditioning program and assigned to one of nine vaccine regimens, each
      consisting of some combinations of killed or modified-live virus vaccines against
      bovine herpesvirus-1 (BHV-1), bovine viral diarrhea virus (BVDV), parainfluenza-3
      (PI-3) virus, and bovine respiratory syncytial virus (BRSV). Serum virus
      neutralization antibody titers were measured at four time points. At the end of
      the study, all vaccinated calves had higher antibody titers to BVDV, BHV-1, and
      PI-3 but not BRSV. Calves on a vaccine program that included at least one dose of
      modified-live virus vaccine had higher virus-neutralizing antibody titers against
      BVDV than did calves receiving only killed vaccines. Calves on a program with a
      combination of modified-live and killed virus vaccines had higher virus
      neutralizing antibody titers to BHV-1 than did calves receiving only killed or
      only modified-live virus vaccine. Preconditioning programs that include
      vaccinations should incorporate modified-live vaccines to maximize virus
      neutralizing antibodies in serum.

PMID- 19750743
TI  - Protective effect of the chondroprotective agent Cosequin DS on bovine articular
      cartilage exposed in vitro to nonsteroidal antiinflammatory agents.
AB  - Studies were conducted to test the hypothesis that exposure of articular
      cartilage to a combination of the "chondroprotective" agents glucosamine
      hydrochloride, low-molecular-weight chondroitin sulfate, and manganese ascorbate
      (Cosequin DS [CDS], Nutramax Laboratories, Inc.) prevents the potentially adverse
      effects of NSAIDs on cartilage. Articular cartilage proteoglycan synthesis and
      degradation were used to monitor in vitro cartilage activity following timed
      exposure to levels of NSAIDs routinely applied in veterinary medicine. Etodolac
      exposure for 144 hours induced significant inhibition of cartilage matrix
      synthesis and increased the rate of matrix breakdown. Addition of CDS reversed
      both activities. Cartilage metabolism was not affected by exposure to
      indomethacin and remained responsive to CDS with an increase in synthetic
      activity. Aspirin significantly stimulated chondrocyte synthetic activity in the
      presence and absence of CDS. Carprofen at therapeutic levels had a mild (15%)
      stimulatory effect on cartilage metabolism and reduced matrix breakdown. Addition
      of CDS significantly accelerated (30%) matrix synthesis. At higher levels
      carprofen was toxic, reducing cell activity by 80%. The data suggest that CDS may
      be a useful adjunct therapy for preservation of articular cartilage by reversing
      the adverse metabolic effects of etodolac and providing accelerated cartilage
      synthetic activity in the presence of therapeutic levels of carprofen.

PMID- 19750744
TI  - Comparison of microbial growth inhibition screening assays with high-pressure
      liquid chromatography for detection of experimentally incurred penicillin G
      residues in calves.
AB  - Twelve calves were fed milk replacer containing 3.33 ppm penicillin G for one
      feeding, and 12 calves were fed the medicated milk replacer once daily at a rate
      of 12% of their body weight for 14 days. Two calves served as controls. Calves
      were slaughtered 4 to 13 hours after being fed. Kidney, liver, muscle, and urine
      samples were assayed for penicillin by high-pressure liquid chromatography
      (HPLC). Penicillin G was not detected in any muscle samples and concentrations of
      penicillin exceeded the tolerance level (0.05 microg/g) in kidney or liver tissue
      from 13 of 24 treated-calf carcasses examined by HPLC. The Live Animal Swab Test
      identified all 13 carcasses with violative drug residues. Using kidney as the
      test matrix, the Swab Test on Premises identified 10 of 13 carcasses with
      violative drug residues, while the Calf Antibiotic Sulfa Test identified seven of
      13 carcasses with violative residues.

PMID- 19750745
TI  - Effects of imidocarb dipropionate in cats with chronic haemobartonellosis.
AB  - The objective of this study was to evaluate the safety and efficacy of imidocarb
      dipropionate administered to cats for clearing chronic Haemobartonella felis
      infections. Imidocarb dipropionate was administered twice at 5.0 mg/kg by
      intramuscular injection 14 days apart to eight cats with chronic, subclinical
      haemobartonellosis. Clinical signs and laboratory parameters were monitored
      throughout the study. Polymerase chain reaction (PCR) for the detection of
      Mycoplasma haemofelis (large form of H. felis) and Mycoplasma haemominutum (small
      form of H. felis) was performed to assess for parasitologic cure. Four of the
      eight cats treated with imidocarb dipropionate became transiently PCR-negative
      after treatment; untreated control cats (n = 2) were persistently PCR-positive.
      Two persistently PCR-negative cats were given one dose of methylprednisolone
      acetate; one was PCR-positive 10 days later. There was no evidence of significant
      toxicity associated with this imidocarb treatment protocol.

PMID- 19750746
TI  - In vitro evaluation of the antimicrobial effect of commercially available
      mastitis medications combined with EDTA-Tris on bacteria that cause mastitis in
      cattle.
AB  - A study was conducted to evaluate the antimicrobial activity of selected
      commercial mastitis medications with and without EDTA-Tris by comparing minimum
      inhibitory concentrations and minimum bactericidal concentrations in vitro.
      Solutions containing 5 mM EDTA/50 mM Tris potentiated the antimicrobial action of
      seven commercially available mastitis medications when reacted in vitro with
      Staphylococcus aureus, Streptococcus uberis, and Pseudomonas aeruginosa. Lesser
      potentiation was observed for Escherichia coli, whereas no potentiation was
      observed for Klebsiella pneumoniae. The incorporation of EDTA-Tris solutions into
      mastitis medications may reduce the amount of antibiotics necessary for therapy
      and may prevent formation of antibiotic-resistant forms.

PMID- 19750747
TI  - Effects of angiotensin-converting enzyme inhibition on plasma aldosterone
      concentration, plasma renin activity, and blood pressure in spontaneously
      hypertensive cats with chronic renal disease.
AB  - Hypertension is commonly associated with chronic renal disease in cats, and
      inappropriate activation of the renin-angiotensin-aldosterone system (RAAS) may
      contribute to the hypertensive state. Angiotensin-converting enzyme (ACE)
      inhibitors are commonly administered when hypertension is present to decrease
      plasma concentrations of angiotensin II and aldosterone, which cause
      vasoconstriction and sodium and water retention, respectively. The study reported
      here was conducted over a 6-month period to assess the effects of two commonly
      prescribed ACE inhibitors, enalapril and benazepril, on the activity of the RAAS
      and blood pressure in 16 spontaneously hypertensive cats with chronic renal
      disease. Plasma aldosterone and plasma renin activity were not significantly
      affected by ACE inhibitors in hypertensive cats, and systolic blood pressure did
      not decrease below 170 mm Hg with ACE inhibitor monotherapy in 14 of 16 cats.
      These results suggest that continued activation of the RAAS is present in
      hypertensive cats despite treatment with an ACE inhibitor, and ACE inhibitors
      should not be used as first-line antihypertensive treatment in hypertensive cats.

PMID- 19750748
TI  - Safety of long-term feeding of dl-alpha-lipoic acid and its effect on reduced
      glutathione:oxidized glutathione ratios in beagles.
AB  - Alpha-lipoic acid is touted as a powerful antioxidant and possibly a
      conditionally essential nutrient in older mammals. The safety and efficacy of dl
      alpha-lipoic acid was evaluated in 30 adult beagles that were evenly randomized
      into five groups, each of which was fed one of five different foods with varying
      inclusion rates of dl-alpha-lipoic acid (0, 150, 1500, 3000, and 4500 ppm). All
      dogs were fed their respective portion of food daily as their sole source of
      nutrition for 6 months. Evaluations included general health, body weight, food
      intake, hematologic and serum biochemical parameters, and glutathione:oxidized
      glutathione (GSH:GSSG) ratios in lymphocytes. No signs of toxicity were observed
      at any except the highest level of dl-alpha-lipoic acid inclusion, and no
      consistent abnormalities were noted in hematologic or biochemical measures at any
      level. There was a significant overall effect (P< .05) of food on the difference
      of GSH:GSSG ratio between Day 84 and Day 0. All inclusions of dl-alpha-lipoic
      acid increased the ratio of GSH:GSSG with the largest numeric improvement
      occurring at the lowest inclusion rate (150 ppm).

PMID- 19750749
TI  - Effect of clindamycin hydrochloride on gingival crevicular fluid and immune
      mediators in beagles.
AB  - Gingivitis and periodontitis, two frequently observed conditions in dogs, are
      primarily caused by bacterial plaque. Gingival crevicular fluid (GCF) and some of
      the biochemical substances contained in it are used diagnostically and to
      evaluate the success of treatment. A double-blind study using a crossover design
      was conducted to evaluate treatment with clindamycin hydrochloride on the amount
      of GCF and concentrations of its immune mediators (leukotriene B4 [LTB4],
      prostaglandin E2 [PGE2], and polymorphonuclear [PMN] elastase) in dogs. Ten dogs
      received clindamycin orally at 11 mg/kg/day for 14 days, and 10 dogs remained
      untreated as controls. After a 5-month rest period, the treatments were reversed.
      At the beginning and end of each series, the volume of GCF was measured and
      plaque and gingival indices were assessed on six reference teeth of each patient.
      Concentrations of LTB4, PGE2, and PMN elastase were determined by ELISA. In both
      series, plaque and gingival indices dropped significantly (P < or = .0001) in
      dogs treated with clindamycin. The volume of GCF also declined significantly (P<
      or = .0001) following treatment and levels of PGE2, PMN elastase, and LTB4 were
      significantly (P < or = .05) reduced in both series. The antimicrobial effect of
      clindamycin is not only due to high levels in the blood and saliva, but also to
      its presence in the gingival crevice.

PMID- 19750750
TI  - Pharmacokinetics of erythromycin ethylsuccinate after intragastric administration
      to healthy foals.
AB  - Plasma concentrations and pharmacokinetics of erythromycin and related compounds
      were determined after administration of erythromycin ethylsuccinate to six
      healthy male foals 3 to 5 months of age. Hay was withheld from the foals
      overnight and erythromycin ethylsuccinate (25 mg/kg of body weight) was
      administered intragastrically. Plasma erythromycin concentrations were determined
      at specific times after drug administration by high-performance liquid
      chromatography assay. Maximum peak plasma concentrations, time to maximum
      concentrations, area under plasma concentration versus time curves, elimination
      half-life, and mean residence time were determined from concentration versus time
      curves. Maximum peak concentration of erythromycin A (0.45 +/- 0.27 microg/ml)
      after administration of erythromycin ethylsuccinate was observed at 2.38 +/- 1.54
      hours after treatment. Concentrations of anhydroerythromycin A were maximal at
      2.2 +/- 2.0 hours and reached a maximum of 2.6 +/- 1.9 microg/ml. Plasma
      concentrations of the ester parent drug (erythromycin ethylsuccinate) were below
      the limit of quantitation (0.1 microg/ml) at all times except 2.5, 2.75, and 5.5
      hours. Levels at those times ranged from 0.1 to 0.144 microg/ml. Erythromycin
      ethylsuccinate appears to be poorly absorbed after oral administration to fasted
      foals. Plasma concentrations of erythromycin A remained below 0.25 microg/ml
      (reported minimum inhibitory concentration for Rhodococcus equi) for less than 4
      hours after intragastric administration of erythromycin ethylsuccinate,
      suggesting that the recommended dosage (25 mg/kg every 6 hours) would be
      suboptimal for treatment of R. equi infections.

PMID- 19750751
TI  - Efficacy of different dosage levels and administration routes of tilmicosin in a
      natural outbreak of infectious bovine keratoconjunctivitis (pinkeye).
AB  - A total of 120 purebred Hereford cattle were selected from a herd on a ranch in
      Argentina that had a severe outbreak of infectious bovine keratoconjunctivitis
      (IBK, pinkeye) caused by Moraxella bovis. The animals were separated into six
      treatment groups: a nonmedicated control group, a group that received
      oxytetracycline at 300 mg injected intrapalpebrally, and four groups that
      received tilmicosin (Micotil, Elanco Animal Health, Indianapolis, IN; one group
      injected intrapalpebrally at 300 mg and three groups injected subcutaneously at
      2.5, 5, and 10 mg/kg body weight, respectively). Animals were individually
      observed for resolution of lesions associated with IBK (ocular discharge,
      blepharospasin, and corneal lesions) every 7 days for 3 weeks. Corneal
      improvement was significantly better (P< or = .05) for all doses and for either
      route of injection for tilmicosin compared with no treatment or treatment with
      oxytetracycline. Tilmicosin given subcutaneously demonstrated a significant (P <
      or = .05) dose response for overall improvement (one or more score improved, none
      worsened). Tilmicosin given subcutaneously at 10 mg/kg was significantly more
      effective than tilmicosin at 2.5 mg/kg, oxytetracycline, and no treatment.
      Results for tilmicosin at 5 mg/kg were numerically better than no treatment, and
      tilmicosin at 10 mg/kg was numerically better than the drug given by
      intrapalpebral injection. Tilmicosin given by subcutaneous injection at 5 or 10
      mg/kg was effective against IBK under the conditions of this study.

PMID- 19750752
TI  - How to make a DNA chip.
AB  - Microarrays are one of the hottest areas in biological research today.
      Microarrays have been mostly applied to nucleic acid analysis, specifically to
      the assessment of which genes are being expressed and at what level. Early
      microarrays were prepared by using photolithographic methods, which were more
      commonly used for integrated circuit ("computer chip") production. Hence the
      colloquial term "DNA chip" came into being. The completion of the sequencing of
      the human genome and that of many other organisms makes the determination of gene
      function an important next step in understanding the role of DNA in the processes
      of life. DNA microarrays are an excellent tool to address this question because
      their numerous probe sites enable the analysis of many genes simultaneously. With
      good experience in this initial use, many further applications of microarrays are
      being developed, including genotyping in research and genetic diagnosis in
      medicine. DNA microarrays have made abundantly clear the power of vast
      parallelism in biological analysis, which is raising interest in other types of
      microarrays (small-molecule, protein). Many applications for DNA microarrays have
      been developed and clearly many more will emerge through the creativity of the
      scientists who use them. In early studies, users produced their own microarrays.
      The apparent power of microarrays has demanded improvements in production
      methods, and technologies from physical sciences and engineering are now being
      applied to DNA chips. Many branches of chemistry can contribute to improved
      methods: from synthetic chemistry (to attach or prepare DNA), to the physical
      chemistry of surfaces, to analytical chemistry (to assess surface reactions).

PMID- 19750753
TI  - N-heterocyclic carbenes: a new concept in organometallic catalysis.
AB  - N-Heterocyclic carbenes have become universal ligands in organometallic and
      inorganic coordination chemistry. They not only bind to any transition metal, be
      it in low or high oxidation states, but also to main group elements such as
      beryllium, sulfur, and iodine. Because of their specific coordination chemistry,
      N-heterocyclic carbenes both stabilize and activate metal centers in quite
      different key catalytic steps of organic syntheses, for example, C-H activation,
      C-C, C-H, C-O, and C-N bond formation. There is now ample evidence that in the
      new generation of organometallic catalysts the established ligand class of
      organophosphanes will be supplemented and, in part, replaced by N-heterocyclic
      carbenes. Over the past few years, this chemistry has been the field of vivid
      scientific competition, and yielded previously unexpected successes in key areas
      of homogeneous catalysis. From the work in numerous academic laboratories and in
      industry, a revolutionary turning point in oraganometallic catalysis is emerging.

PMID- 19750754
TI  - Chemists and biochemists during the National Socialist era.
AB  - Chemistry and biochemistry in Germany was notably affected by the dismissal and
      emigration of Jewish scientists. The expulsion of Jewish scientists aided to
      significantly reduce the international regard for German science, particularly in
      biochemistry, physical chemistry, and quantum chemistry, after 1945. In most
      cases remaining scientists adjusted quickly after 1933 to the new political
      circumstances, with a few exceptions. A number of them even actively supported
      the politics of National Socialism. This fact as well as the common stance to
      forget the 12 years of National Socialist rule complicated the exchange of
      international scientific knowledge after 1945 and delayed affiliation of the
      weakened fields of research to the level of international research.

PMID- 19750755
TI  - Dendritic polymers in biomedical applications: from potential to clinical use in
      diagnostics and therapy.
AB  - Dendrimers are characterized by a combination of high end-group functionality and
      a compact, precisely defined molecular structure. These characteristics can be
      used in biomedical applications, for example, for the amplification or
      multiplication of effects on a molecular level, or to create extremely high local
      concentrations of drugs, molecular labels, or probe moieties. A brief summary of
      the current state of the art in the field is given, and focuses on the
      application of dendrimers both in diagnostics as well as in therapy. In
      diagnostics, dendrimers that bear GdIII complexes are used as contrast agents in
      magnetic resonance imaging. DNA dendrimers have potential for routine use in high
      throughput functional genomic analysis, as well as for DNA biosensors. Dendrimers
      are also being investigated for therapeutics, for example, as carriers for
      controlled drug delivery, in gene transfection, as well as in boron neutron
      capture therapy. Furthermore, the antimicrobial activity of dendrimers has been
      studied.

PMID- 19750756
TI  - New methods for the high-throughput screening of enantioselective catalysts and
      biocatalysts.

PMID- 19750757
TI  - Water-soluble stimuli-responsive vesicles from peptide-based diblock copolymers.

PMID- 19750758
TI  - Dual biosensing by magneto-controlled bioelectrocatalysis.

PMID- 19750759
TI  - Cavity-directed, highly stereoselective [2+2] photodimerization of olefins within
      self-assembled coordination cages.

PMID- 19750760
TI  - Adhesive and anti-adhesive agents in giant vesicles.

PMID- 19750761
TI  - Electrochemical modification of single carbon nanotubes.

PMID- 19750762
TI  - Selective complexation of N-alkylpyridinium salts: recognition of NAD+ in water.

PMID- 19750764
TI  - Enantioselective C-C bond formation with titanium(IV) alkoxides--an unusual
      alkylation.

PMID- 19750763
TI  - From classical to nonclassical metal-boron bonds: synthesis of a novel
      metallaborane.

PMID- 19750765
TI  - A defined N-heterocyclic carbene complex for the palladium-catalyzed Suzuki cross
      coupling of aryl chlorides at ambient temperatures.

PMID- 19750766
TI  - X-ray structural characterization of a monoorganotin acid.

PMID- 19750767
TI  - Additivity and quantification of dispersive interactions--from cyclopropyl to
      nitro groups: measurements on porphyrin derivatives.

PMID- 19750768
TI  - An azulene analogue of the tripyrranes and carbaporphyrinoids therefrom.

PMID- 19750770
TI  - Phase-sensitive supramolecular chirogenesis in bisporphyrin systems.

PMID- 19750769
TI  - A practical oligomeric [(salen)Co] catalyst for asymmetric epoxide ring-opening
      reactions.

PMID- 19750771
TI  - Stereoselective total synthesis of epothilones by the metathesis approach
      involving C9-C10 bond formation.

PMID- 19750772
TI  - [Co5(im)10 x 2MB]infinity: a metal-organic open-framework with zeolite-like
      topology.

PMID- 19750773
TI  - HIO3 and I2O5: mild and selective alternative reagents to IBX for the
      dehydrogenation of aldehydes and ketones.

PMID- 19750774
TI  - Generation of organotantalum reagents and conjugate addition to enones.

PMID- 19750775
TI  - Total synthesis of (+)-pamamycin-607.

PMID- 19750776
TI  - Proton-coupled electron transfer from phosphorus: a P-H/P-D kinetic isotope
      effect of 178.

PMID- 19750777
TI  - A new crystal modification of chromium tetrafluoride: beta-CrF4.

PMID- 19750778
TI  - Sequential base-promoted annulation/ palladium-catalyzed domino 1,5-enyne
      arylation and vinylation of alpha-propargylaminohydrazones.

PMID- 19750779
TI  - The first isolable 4-silatriafulvene.

PMID- 19750780
TI  - Aldolase-catalyzed asymmetric synthesis of novel pyranose synthons as a new entry
      to heterocycles and epothilones.

PMID- 19750782
TI  - From vinyl sulfides, sulfoxides, and sulfones to vinyl transition metal
      complexes.

PMID- 19750781
TI  - Convergent synthesis of silylated allylic alcohols by a stereoselective domino,
      sequential radical-coupling reaction.

PMID- 19750783
TI  - Polymeric surfactants for the new millennium: a pH-responsive, zwitterionic,
      schizophrenic diblock copolymer.

PMID- 19750784
TI  - A selective chromogenic reagent for nitrate.

PMID- 19750785
TI  - Selective recognition of fluoride anion using a Li(+)--metallacrown complex.

PMID- 19750786
TI  - Cyclo[8]pyrrole: a simple-to-make expanded porphyrin with no meso bridges.

PMID- 19750787
TI  - C-C coupling between an eta3-allyl ligand and carbon nucleophiles in molybdenum
      and tungsten complexes: structural characterization of the key intermediate.

PMID- 19750788
TI  - The stable pentamethylcyclopentadienyl cation.

PMID- 19750789
TI  - On the interaction between N-heterocyclic carbenes and organic acids: structural
      authentication of the first N-H...C hydrogen bond and remarkably short C-H...O
      interactions.

PMID- 19750790
TI  - An efficient stereoselective total synthesis of DL-sesquicillin, a glucocorticoid
      antagonist.

PMID- 19750791
TI  - The interaction of cognitive load and attention-directing cues in driving.
AB  - OBJECTIVE: This study investigated the effect of a nondriving cognitively loading
      task on the relationship between drivers' endogenous and exogenous control of
      attention. BACKGROUND: Previous studies have shown that cognitive load leads to a
      withdrawal of attention from the forward scene and a narrowed field of view,
      which impairs hazard detection. METHOD: Posner's cue-target paradigm was modified
      to study how endogenous and exogenous cues interact with cognitive load to
      influence drivers' attention in a complex dynamic situation. In a driving
      simulator, pedestrian crossing signs that predicted the spatial location of
      pedestrians acted as endogenous cues. To impose cognitive load on drivers, we had
      them perform an auditory task that simulated the demands of emerging in-vehicle
      technology. Irrelevant exogenous cues were added to half of the experimental
      drives by including scene clutter. RESULTS: The validity of endogenous cues
      influenced how drivers scanned for pedestrian targets. Cognitive load delayed
      drivers' responses, and scene clutter reduced drivers' fixation durations to
      pedestrians. Cognitive load diminished the influence of exogenous cues to attract
      attention to irrelevant areas, and drivers were more affected by scene clutter
      when the endogenous cues were invalid. CONCLUSION: Cognitive load suppresses
      interference from irrelevant exogenous cues and delays endogenous orienting of
      attention in driving. APPLICATION: The complexity of everyday tasks, such as
      driving, is better captured experimentally in paradigms that represent the
      interactive nature of attention and processing load.

PMID- 19750792
TI  - Trust and reliance on an automated combat identification system.
AB  - OBJECTIVE: We examined the effects of aid reliability and reliability disclosure
      on human trust in and reliance on a combat identification (CID) aid. We tested
      whether trust acts as a mediating factor between belief in and reliance on a CID
      aid. BACKGROUND: Individual CID systems have been developed to reduce friendly
      fire incidents. However, these systems cannot positively identify a target that
      does not have a working transponder. Therefore, when the feedback is "unknown",
      the target could be hostile, neutral, or friendly. Soldiers have difficulty
      relying on this type of imperfect automation appropriately. METHOD: In manual and
      aided conditions, 24 participants completed a simulated CID task. The reliability
      of the aid varied within participants, half of whom were told the aid reliability
      level. We used the difference in response bias values across conditions to
      measure automation reliance. RESULTS: Response bias varied more appropriately
      with the aid reliability level when it was disclosed than when not. Trust in aid
      feedback correlated with belief in aid reliability and reliance on aid feedback;
      however, belief was not correlated with reliance. CONCLUSION: To engender
      appropriate reliance on CID systems, users should be made aware of system
      reliability. APPLICATION: The findings can be applied to the design of
      information displays for individual CID systems and soldier training.

PMID- 19750793
TI  - Interrater reliability of posture observations.
AB  - OBJECTIVE: The aims of this research were (a) to study the interrater reliability
      of a posture observation method, (b) to test the impact of different posture
      categorization systems on interrater reliability, and (c) to provide guidelines
      for improving interrater reliability. BACKGROUND: Estimation of posture through
      observation is challenging. Previous studies have shown varying degrees of
      validity and reliability, providing little information about conditions necessary
      to achieve acceptable reliability. METHOD: Seven raters estimated posture angles
      from video recordings. Different measures of interrater reliability, including
      percentage agreement, precision, expression as interrater standard deviation, and
      intraclass correlation coefficients (ICC), were computed. RESULTS: Some posture
      parameters, such as the upper arm flexion and extension, had ICCs > or = 0.50.
      Most posture parameters had a precision around the 10 degrees range. The
      predefined categorization and 300 posture categorization strategies showed
      substantially better agreement among the raters than did the 10 degrees strategy.
      CONCLUSIONS: Different interrater reliability measures described different
      aspects of agreement for the posture observation tool. The level of agreement
      differed substantially between the agreement measures used. Observation of large
      body parts generally resulted in better reliability. Wider width angle intervals
      resulted in better percentage agreement compared with narrower intervals. For
      most postures, 30 degrees-angle intervals are appropriate. Training aimed at
      using a properly designed data entry system, and clear posture definitions with
      relevant examples, including definitions of the neutral positions of the various
      body parts, will help improve interrater reliability. APPLICATION: The results
      provide ergonomics practitioners with information about the interrater
      reliability ofa postural observation method and guidelines for improving
      interrater reliability for video-recorded field data.

PMID- 19750794
TI  - Comparisons of musculoskeletal complaints and data entry between a sitting and a
      sit-stand workstation paradigm.
AB  - BACKGROUND: Seated working positions are often regarded as a cause for discomfort
      in the musculoskeletal system. Performing work in different working positions-
      that is, alternating between sitting and standing (sit-stand workstation
      paradigm)--could help reduce physical complaints. OBJECTIVE: The questions were
      whether performing office work partly in a standing position leads to reduced
      complaints and whether standing would change the efficiency of data entry office
      work. METHOD: We investigated the effect of a sit-stand workstation paradigmd
      during experimental data entry office work on physical and psychological
      complaints and data entry efficiency by conducting a randomized controlled trial
      with 60 male participants ages 18 to 35 years. RESULTS: In this experiment,
      musculoskeletal complaints were reduced by a sit-stand workstation paradigm. A
      trend could be identified indicating a small but nonsignificant loss of
      efficiency in data entry while standing. CONCLUSION: A sit-stand workstation
      paradigm reduces musculoskeletal complaints without considerably affecting data
      entry efficiency under the presented study conditions (young male participants,
      short duration, fixed and controlled sit-stand workstation paradigm, simulated
      experimental working condition). APPLICATION: According to the present data,
      implementing a sit-stand workstation paradigm can be an effective workplace
      health intervention to reduce musculoskeletal complaints. This experiment
      encourages further studies on the effectiveness of a sit-stand workstation
      paradigm. Experimental research and field studies that prove the reduction of
      complaints when introducing a sit-stand workstation paradigm in the workplace
      could be the basis for evidence-based recommendations regarding such
      interventions.

PMID- 19750795
TI  - Cognitive models of the influence of color scale on data visualization tasks.
AB  - OBJECTIVE: Computational models of identification and relative comparison tasks
      performed on color-coded data visualizations were presented and evaluated against
      two experiments. In this context, the possibility of a dual-use color scale,
      useful for both tasks, was explored, and the use of the legend was a major focus.
      BACKGROUND: Multicolored scales are superior to ordered brightness scales for
      identification tasks, such as determining the absolute numeric value of a
      represented item, whereas ordered brightness scales are superior for relative
      comparison tasks, such as determining which of two represented items has a
      greater value. METHOD: Computational models were constructed for these tasks, and
      their predictions were compared with the results of two experiments. RESULTS: The
      models fit the experimental results well. A multicolored, brightness-ordered dual
      use scale supported high accuracy on both tasks and fast responses on a
      comparison task but relatively slower responses on the identification task.
      CONCLUSION: Identification tasks are solved by a serial visual search of the
      legend, whose speed and accuracy are a function of the discriminability of the
      color scales. Comparison tasks with multicolored scales are performed by a
      parallel search of the legend; with brightness scales, comparison tasks are
      generally solved by a direct comparison between colors on the visualization,
      without reference to the legend. Finally, it is possible to provide users a dual
      use color scale effective on both tasks. APPLICATION: Trade-offs that must
      typically be made in the design of color-coded visualizations between speed and
      accuracy or between identification and comparison tasks may be mitigated.

PMID- 19750796
TI  - Uni- and interdisciplinary effects on round and handover content in intensive
      care units.
AB  - OBJECTIVE: The aim of this study was to explore differences in the verbal content
      of handovers and rounds conducted in uni- and interdisciplinary social contexts.
      We expected higher proportions of goals to be articulated during
      interdisciplinary rounds. BACKGROUND: Lack of explanatory connections between
      round improvement initiatives and outcomes suggest insufficient understanding
      about health care communications, especially the role of social interaction.
      METHODS: The recognition-primed abstract decomposition space (RP-ADS) was used to
      analyze the information content of nurse handovers and morning rounds in a
      unidisciplinary- (physicians only) and an interdisciplinary-round intensive care
      unit (ICU). Data were collected using audio recordings of rounds and handovers
      for five patients for 5 days each in both ICUs. RESULTS: Hierarchical log-linear
      analyses show strong associations between events (medical rounds vs. nurses'
      shift handovers), type (uni- vs. interdisciplinary), and focus (levels of the RP
      ADS) with highly significant combined two-way and higher-order interactions,
      LRchi2(df=4) = 30.91, p < .0001. All tests of partial association were also
      highly significant. Differences among levels of the variables were evaluated
      using standardized residuals. CONCLUSION: Nurses focused on RP-ADS data and
      intervention levels, whereas physicians focused on diagnoses and expectations.
      Clinical goals that integrate these orientations emerged to a greater extent in
      interdisciplinary rounds. In addition, social context of rounds appears to
      influence nurse handovers. Unidisciplinary ICU nurse handovers consisted of a
      series of data- and intervention-related observations, whereas ICU nurse
      handovers in interdisciplinary ICUs tended to integrate data, interventions and
      clinical goals. APPLICATION: These results are relevant to the design and
      implementation of clinical communication improvement initiatives and support
      tools.

PMID- 19750797
TI  - Coordination and continuity of intensive care unit patient care.
AB  - OBJECTIVE: Using Klein's model of team coordination, we explored the null
      hypothesis that intensive care unit (ICU) care coordination unfolds as a linear
      sequence. Our intent was to generate hypotheses for further research and to
      provide interim recommendations for improving care coordination. We also explored
      factors contributing to care coordination (e.g., role responsibilities, support
      tools). BACKGROUND: Although the body of clinical communications research is
      considerable, few studies address broader team processes in real-world
      environments; hence, these processes are not well understood. METHODS: All
      bedside communications for 5 ICU patients were recorded for 5 days per patient
      and were coded using Klein's model. Markov analysis was used to describe the care
      coordination process. Multivariate contingency table analysis and standardized
      parameter estimates described important contributing factors, and support tools
      were described using descriptive statistics. RESULTS: First-, second-, and third
      order Markov analyses show that care coordination does not unfold as a linear
      sequence; however, Markov diagrams suggest some process structure. Standardized
      parameter estimates of factors contributing to care coordination were calculated
      from a statistically significant three-way model (chi2[df= 18] = 36.95, p <
      .005). Role-based differences depend on context, with important differences in
      contributions to care coordination occurring within rounds. Tools supported only
      48% of conversations. CONCLUSION: Three alternative research hypotheses were
      defined with at least a minimal level of support. Testing these hypotheses
      present substantial theoretical, methodological, and data analysis challenges.
      APPLICATION: Within a research framework, recommendations for change could
      achieve significant gains for understanding and for reducing breakdowns in care
      coordination.

PMID- 19750798
TI  - Individual differences in route-learning strategy and associated working memory
      resources.
AB  - OBJECTIVE: The current investigation examined individual differences in route
      learning strategies and their relative demands on visuospatial versus verbal
      working memory (WM) resources in virtual environments. BACKGROUND: Learning new
      routes is a resource-demanding activity that must often be carried out in
      conjunction with other concurrent tasks. Virtual environments (VEs) are
      increasingly being used for training and research, pointing to the importance of
      determining the strategies people use to learn routes in these environments.
      METHODS: Participants classified as having good or poor sense of direction (SOD)
      attempted to learn novel routes while concurrently performing either a verbal
      (articulatory suppression) or a visuospatial (tapping) WM interference task.
      RESULTS: Different navigational strategies were observed in each SOD group.
      Individuals with poor SOD relied more heavily on verbal rather than visuospatial
      WM resources, as evidenced by greater disruption to route-learning performance
      from the articulatory suppression task relative to the tapping task. Conversely,
      individuals with good SOD exhibited more route-learning disruption from the
      tapping task, suggesting a greater reliance on visuospatial WM resources.
      CONCLUSION: Individuals differ from one another in the strategies they use and
      the WM resources they tap--verbal or visuospatial--to learn routes in VEs. Self
      report measures can be used as indices of such individual differences in
      navigational strategy use in VE tasks. APPLICATION: Assessing SOD and associated
      WM resources have implications for targeted training for navigation in VEs and
      for the design of in-vehicle navigation systems.

PMID- 19750799
TI  - Can headway reduction in fog be explained by impaired perception of relative
      motion?
AB  - OBJECTIVE: The goal of this study was to provide a better understanding of driver
      behavior in fog. BACKGROUND: Impaired perception of changes in headway is
      hypothesized to be one of the reasons for shorter following distances in foggy
      conditions as compared with clear weather. METHOD: In the experiments described
      here, we measured response time for discriminating between whether the vehicle
      ahead is getting closer or farther away. Several visibility conditions were
      studied, ranging from a no-fog condition to a condition in which the vehicle
      could be seen only by its rear fog lights. RESULTS: Fog conditions increased
      response times when the outline of the vehicle was barely visible or not visible
      at all. The longer response times in fog were attributable to the low contrast of
      the vehicle outline when still visible and to the smaller spacing between the two
      lights when the outline could not be properly perceived. Moreover, response times
      were found to be shorter for shorter following distances and for faster
      accelerations. CONCLUSION: Reducing headway could be a way for drivers to achieve
      faster discrimination of relative motion in foggy weather. More specifically,
      shortening one's following distance until visibility of the lead vehicle changes
      from bad to good may have a perceptual control benefit, insofar as the response
      time gain compensates for the reduction in headway under these conditions.
      APPLICATIONS: Potential applications include improving traffic safety. The
      results provide a possible explanation for close following in fog and point out
      the importance of rear-light design under these conditions.

PMID- 19750800
TI  - Viewpoint animation with a dynamic tether for supporting navigation in a virtual
      environment.
AB  - OBJECTIVE: This study examined the concept of dynamic viewpoint tethering for
      enhancing performance in 3-D avatar control tasks. BACKGROUND: Dynamic viewpoint
      tethering refers to a viewpoint animation technique that couples a display
      viewpoint to a controlled avatar through a virtual tether. A dynamic tether,
      modeled as a mass spring damper system, can potentially generate desirable
      viewpoint behavior because of its ability to produce frequency-separated
      viewpoint responses. This study investigated the impact of a tether's rigidity
      and damping properties on users' navigational performance. METHODS: Twelve
      participants took part in a simulated 3-D aerial navigational task. Performance
      was evaluated with respect to local guidance and global awareness. RESULTS: Root
      mean square error scores revealed a decrease in local guidance performance when
      (a) the tether was either severely underdamped or overdamped and (b) the tether's
      rigidity approached either zero or infinity. In addition, (c) global performance
      was better for higher-frequency forcing functions. CONCLUSION: Critical damping
      and medium rigidity can be optimized during design for enhancing users'
      navigational efficiency. APPLICATION: Guidelines generated from this study
      support future viewpoint design in interactive virtual reality applications.

PMID- 19750801
TI  - Cardiac autonomic control during simulated driving with a concurrent verbal
      working memory task.
AB  - OBJECTIVE: The objective of the study was to illustrate sensitivity and
      diagnosticity differences between cardiac measures and lane-keeping measures of
      driving performance. BACKGROUND: Previous research suggests that physiological
      measures can be sensitive to the effects of driving and side task performance and
      diagnostic of the source of the attentional demands. We hypothesized that
      increases in side task difficulty would elicit physiological change without
      reduction of driving task performance and that the side task demands would elicit
      patterns ofautonomic activity that map to specific attentional processing
      resources. METHOD: Separately and concurrently, thirty-two participants performed
      a simulated driving task and verbal working memory task (with two levels of
      difficulty, 0 back and 3 back) separately and concurrently. Attentional demands
      were assessed through physiological and performance measures. RESULTS: Cardiac
      measures reflected changes in attentional demand from single- to dual-task
      driving with an n-back task, whereas lane-keeping measures did not. Furthermore,
      patterns of autonomic activity elicited by driving, n-back task, and dual-task
      driving with a 3-back task were consistent with our predictions about autonomic
      activity. CONCLUSION: Changes in cardiac measures without changes in lane-keeping
      measures provide evidence that cardiac measures can be sensitive to hidden costs
      in attention that do not manifest in coarse measures of driving performance.
      Furthermore, correct predictions regarding the patterns of autonomic activity
      elicited suggests that cardiac measures can serve as diagnostic tools for
      attention assessment. APPLICATION: Because of the demonstrated differences in
      sensitivity and diagnosticity, researchers should consider the use of cardiac
      measures in addition to driving performance measures when studying attention in a
      driving simulator environment.

PMID- 19750802
TI  - Can metric feedback training hinder actions involving distance?
AB  - OBJECTIVE: The present studies tested whether distance estimation training with
      metric feedback can degrade the performance of untrained primarily perceptual
      motor tasks. BACKGROUND: Training with metric feedback can improve distance
      estimations. However, previous research led to the conclusion that those
      improvements stemmed from changes in cognitive processing rather than in
      perception. If trainees applied their new cognitive strategies to primarily
      perceptual-motor tasks, then the performance of those tasks should degrade. The
      present studies tested that possibility. METHOD: Experiment 1 sought to replicate
      that training with metric feedback would improve metric distance estimations.
      Experiments 2 and 3 investigated whether such training would degrade the
      performance of a primarily perceptual-motor task. Experiment 4 investigated
      whether such training would affect a perceptual-motor task that required
      cognition. RESULTS: Metric feedback improved metric distance estimation
      (Experiments 1-4) and throwing to a specified distance (Experiment 4). Metric
      feedback degraded throwing to a target (Experiments 2 and 3), although that
      effect was not evident when pretesting was omitted (Experiment 3). CONCLUSION: If
      distance estimation trainees apply what they learned from metric feedback to
      untrained primarily perceptual-motor tasks, then the performance of those tasks
      will suffer. However, if trainees apply what they learned to untrained tasks that
      require metric estimation, then the performance of those tasks will improve.
      APPLICATION: Distance estimation training with metric feedback may not generalize
      to other tasks and may even degrade performance on certain tasks. Future research
      must specify the conditions under which distance estimation training with metric
      feedback leads to performance improvements and decrements.

PMID- 19750803
TI  - Parvo-like virus in the hepatopancreas of freshwater prawns Macrobrachium
      rosenbergii cultivated in Thailand.
AB  - A survey of cultivated giant freshwater prawns Macrobrachium rosenbergii from
      Thailand revealed the presence of unusual spherical to ovoid inclusions in nuclei
      of hepatopancreas tubule epithelial cells. These began as small eosinophilic
      inclusions that became more basophilic as they increased in size. They were
      present in both R-cells and E-cells but were largest and deeply basophilic only
      in the E-cells. Confocal laser microscopy revealed that stained nucleic acid
      fluorescence from the inclusions was lost by treatment with DNase I specific for
      double- and single-stranded DNA and also lost or reduced by treatment with
      mungbean nuclease specific for single-stranded nucleic acids. Transmission
      electron microscopy (TEM) revealed that the inclusions contained tightly packed,
      unenveloped, viral-like particles of approximately 25 to 30 nm diameter,
      resembling those produced by shrimp parvoviruses. However, PCR, in situ
      hybridization and immunohistochemical tests for shrimp parvoviruses previously
      reported from Thailand were all negative. These results suggested that the
      inclusions contained a parvo-like virus, not previously reported from M.
      rosenbergii in Thailand.

PMID- 19750804
TI  - Macrobrachium rosenbergii nodavirus disease (white tail disease) in Australia.
AB  - The index case of white tail disease (WTD) is presented in adult broodstock
      prawns Macrobrachium rosenbergii from the Flinders River in western Queensland,
      Australia, in mid-2007. Histological examination revealed extensive myonecrosis
      with massive infiltration of myonuclei and some haemocytes. Juveniles from the
      same broodstock but not from 3 other families displayed white muscle lesions. Low
      grade chronic mortalities approaching 100% over 1 yr occurred. Reverse
      transcriptase polymerase chain reactions (RT-PCR) were attempted for both M.
      rosenbergii nodavirus (MrNV) with 2 sets of primers and for the satellite virus,
      extrasmall virus (XSV). All 3 PCRs generated amplicons of the expected sizes.
      Basic local alignment search tool (BLAST) analyses of the 3 consensus sequences
      identified a 91% match with MrNV viral capsid protein gene, 96% match with MrNV
      RNA-directed RNA polymerase gene, and a 99% match with M. rosenbergii XSV capsid
      protein gene. The clinical signs, histopathological lesions and RT-PCR amplicons
      could be reproduced in M. rosenbergii inoculated with cell-free extracts
      fulfilling River's postulates. We conclude that this is an endemic strain of MrNV
      as the sequences are dissimilar to strains of MrNV circulating around Asia and
      the Americas. This case only poorly meets the Office International des Epizooties
      (OIE) case definition for WTD due to the age of the prawns involved and the
      nature of the inclusion bodies. Perhaps the OIE case definition needs broadening.

PMID- 19750805
TI  - Historical presence (1975-1985) of mycobacteriosis in Chesapeake Bay striped bass
      Morone saxatilis.
AB  - A retrospective analysis of archived tissue blocks has revealed that
      mycobacteriosis was apparent in Chesapeake Bay striped bass as early as 1984. Of
      37 cases available from the years 1975 to 1985, 2 fish were found positive based
      on histopathology and genus-specific PCR. Multi-gene sequencing places the
      bacteria from the 2 positive cases (1984 and 1985) within the Mycobacterium
      tuberculosis clade with closest resemblance to the recently described fish
      pathogen M. pseudoshottsii. Our data confirms that mycobacteriosis is not a new
      disease of Chesapeake Bay striped bass and underscores the value of archived
      tissues in epidemiological examinations.

PMID- 19750806
TI  - Enhanced mortality in Nile tilapia Oreochromis niloticus following coinfections
      with ichthyophthiriasis and streptococcosis.
AB  - Ichthyophthirius multifiliis Fouquet (Ich) and Streptococcus iniae are 2 major
      pathogens of cultured Nile tilapia Oreochromis niloticus (L). Currently there is
      no information available for the effect of coinfection by Ich and S. iniae on
      fish. The objective of this study was to determine the effects of parasite load
      and Ich development size on fish mortality following S. iniae infection. Low
      mortality (< or =20%) was observed in tilapia exposed to Ich or S. iniae alone.
      Mortalities increased from 38% in tilapia exposed to Ich at 10,000 theronts fish(
      1) to 88% in fish at 20,000 theronts fish(-1) following S. iniae exposure. The
      median days to death were significantly fewer (7 d) in fish exposed to Ich at
      20,000 theronts fish(-1) than fish exposed to 10,000 theronts fish(-1) (10 d). A
      positive correlation (correlation coefficient = 0.83) was noted between tilapia
      mortality and size of Ich trophonts at the time of S. iniae challenge. Fish
      parasitized with well-developed trophonts (Day 4, 2 x 10(7) microm3 in volume)
      suffered higher mortality (47.5%) than fish (10.0%) infested by young trophonts
      (Hour 4, 1.3 x 10(4) microm3 in volume) after S. iniae challenge. The results of
      this study demonstrated that both parasite load and trophont size increased
      susceptibility and mortality of tilapia to S. iniae infection.

PMID- 19750807
TI  - Transmission of the parasitic dinoflagellate Hematodinium sp. infection in blue
      crabs Callinectes sapidus by cannibalism.
AB  - Infection with the parasitic dinoflagellate Hematodinium sp. can be devastating
      to blue crab Callinectes sapidus populations. Morbidity and mortality appear to
      depend on the burden of parasitic organisms. Heavily infected crabs become
      lethargic and, if not preyed upon, succumb to overwhelming infection. We report
      on the transmission of Hematodinium sp. into blue crabs that were fed pieces of
      infected tissues and examined for evidence of infection at time periods from 1 to
      48 h and for the general state of their health after 4 d. During the first 16 h
      after feeding, Hematodinium sp. was found in the gut, followed by large increases
      in hemolymph hemocytes and the appearance of hemocytic nodules in tissues. By 16
      h, the hemocytic nodules appeared poorly circumscribed and disorganized. No
      nodules were seen in a heavily infected crab after 24 h. By the end of the 48 h
      after feeding, 73% (11 of 15) of the crabs had shown evidence of infection with
      Hematodinium sp. Those crabs with infection intensities (Hematodinium sp. as
      percent of cells in hemolymph) higher than 20% were dead within 4 d.

PMID- 19750808
TI  - Ultrastructure of Bonamia sp. in Ostrea chilensis in Chile.
AB  - Oyster Ostrea chilensis samples were collected from Quihua Island, Chile, in
      December 2003 and February 2005, and examined in May 2004, and March, April and
      July 2005, for an ultrastructural comparison of the Chilean Bonamia sp. with
      other Bonamia spp. Only uni-nucleate stages were encountered, except in the July
      sample. The Chilean parasite differs from B. perspora in the apparent lack of a
      plasmodial stage and of sporulation. It resembles B. ostreae in size, the low
      number of mitochondrial profiles, and the prevalence and mean number of lipid
      droplets. It differs from B. ostreae in the greater prevalence of nuclear
      membrane-bound Golgi (NM-BG), associated haplosporogenesis, and smaller size of
      haplosporosomes. The Chilean Bonamia sp. resembles B. exitiosa in the number of
      haplosporosomes, prevalence of lipid droplets, anastomosing endoplasmic reticulum
      and NM-BG, presence of circles of smooth endoplasmic reticulum (sER), confronting
      cisternae (CC), and cylindrical CC (CCC). It also appears to have a similar
      developmental cycle to B. exitiosa with larger forms occurring in winter
      (August). The circles of sER, CC, and CCC have only been reported from B.
      exitiosa, and it appears that Chilean Bonamia sp. and B. exitiosa are more
      closely related than they are to B. perspora or B. ostreae. Similarities in
      ultrastructure and developmental stages between New Zealand and Chilean parasites
      suggest that the 2 species are related, and that the Chilean Bonamia sp. is
      either B. exitiosa, a sub-species of B. exitiosa, or a separate species closely
      related to B. exitiosa.

PMID- 19750809
TI  - Long-term parasitic association between the boring polychaete Polydora
      bioccipitalis and Mesodesma donacium.
AB  - Polydora and related genera are common pests for molluscs. Establishing
      differences between native species and recent invaders provides the basis for
      understanding the effect of parasites and has implications for resource
      management. P. biocipitalis has been reported as a recently introduced species to
      the Chilean-Peruvian coast, raising concerns about its threat to native bivalve
      species. In contrast, studies on the infestation of P. bioccipitalis on the surf
      clam Mesodesma donacium, one of the most important species for shellfisheries,
      suggest a long-term parasitic relationship. The present study analyses infested
      (i.e. blistered) fossil shells of M. donacium deposited during the Holocene and
      Middle Pleistocene epochs and critically reviews evidence supporting the
      hypothesis of the recent introduction of P. bioccipitalis to the Chilean-Peruvian
      coast. The blistering pattern seen on fossil and recent shells can be considered
      species-specific for the infestation of M. donacium by P. bioccipitalis. No
      evidence was actually found on vectors, introduction pathways or distribution
      range to support the status of P. bioccipitalis as an introduced species. On the
      contrary, our findings point to a long-term association, at least for several
      hundred thousand years, between M. donacium and P. bioccipitalis.

PMID- 19750810
TI  - CO2-fixing enzymes and phosphoenolpyruvate metabolism in the fish parasite
      Hysterothylacium aduncum (Ascaridoidea, Anisakidae).
AB  - CO2 stimulates the development of many of the intestinal helminths that are able
      to fix CO2 by means of phosphoenolpyruvate carboxykinase (PEPCK), such as
      Hysterothylacium aduncum. We determined the activity of CO2-fixing enzymes such
      as PEPCK and phosphoenolpyruvate carboxylase (PEPC), although no significant
      activity was detected for pyruvate carboxylase or carboxylating-malic enzyme. The
      former act on phosphoenolpyruvate (PEP) to yield oxalacetate. In the helminths
      studied, PEP has a vital role in glucidic metabolism. Consequently, we determined
      the activity of other enzymes involved in the crossroad of PEP, such as pyruvate
      kinase (PK), lactate dehydrogenase and malate dehydrogenase. All enzymes detected
      showed significant variations in activity during the in vitro development of the
      parasite from the third larval stage to mature adult. Fixing of CO2 by PEPCK
      decreased during development (from 228 to 115 nmol min(-1) mg(-1) protein), while
      that by PEPC increased (from 19 to 46 nmol min(-1) mg(-1) protein). This enzyme,
      which is rare in animals, could play a part in detecting levels of free
      phosphate, releasing it from PEP when required for processes such as
      glycogenolysis, glycolysis and adenosine 5'-triphosphate (ATP) synthesis. PK,
      which showed increasing activity during development up to immature adult (from 56
      to 82 nmol min(-1) mg(-1) protein), could act in combination with PEPC to obtain
      energy in the cytosol (in the form of ATP) and in the mitochondria (possible
      destination of the pyruvate formed), compensating for the decrease in activity of
      PEPCK.

PMID- 19750811
TI  - Epidemiological pattern of tattoo skin disease: a potential general health
      indicator for cetaceans.
AB  - The presence of tattoo skin disease (TSD) was examined in 1392 free-ranging and
      dead odontocetes comprising 17 species from the Americas, Europe, South Africa,
      New Zealand and Greenland. We investigated whether TSD prevalence varied with
      sex, age and health status. TSD was encountered in cetaceans from the Pacific and
      Atlantic Oceans as well as in those from the North, Mediterranean and Tasman
      Seas. No clear patterns related to geography and host phylogeny were detected,
      except that prevalence of TSD in juveniles and, in 2 species (dusky dolphin
      Lagenorhynchus obscurus and Burmeister's porpoise Phocoena spinipinnis), in
      adults was remarkably high in samples from Peru. Environmental factors and virus
      properties may be responsible for this finding. Sex did not significantly
      influence TSD prevalence except in the case of Peruvian P. spinipinnis.
      Generally, there was a pattern of TSD increase in juveniles compared to calves,
      attributed to the loss of maternal immunity. Also, in most samples, juveniles
      seemed to have a higher probability of suffering TSD than adults, presumably
      because more adults had acquired active immunity following infection. This holo
      endemic pattern was inverted in poor health short-beaked common dolphins
      Delphinus delphis and harbour porpoises Phocoena phocoena from the British Isles,
      and in Chilean dolphins Cephalorhynchus eutropia from Patagonia, where adults
      showed a higher TSD prevalence than juveniles. Very large tattoos were seen in
      some adult odontocetes from the SE Pacific, NE Atlantic and Portugal's Sado
      Estuary, which suggest impaired immune response. The epidemiological pattern of
      TSD may be an indicator of cetacean population health.

PMID- 19750812
TI  - Influence of Cu2+-loaded silicate on the growth performance and microflora of
      crucian carp Carassius auratus.
AB  - We investigated the effects of Cu2+-loaded silicate (CLS) on the growth
      performance, microflora of skin, gill and intestine, and intestinal morphology of
      crucian carp Carassius auratus. A total of 225 native wild crucian carp, with an
      average initial body weight of 20 g, were randomly divided into 5 treatment
      groups using 3 replicate tanks of 15 fish per group. The dietary treatments were
      (1) basal diet, (2) basal diet + CuSO4, (3) basal diet + silicate, (4) basal diet
      + 0.5% CLS and (5) basal diet + 50 mg kg(-1) chlortetracycline (CTC, purity
      98.8%). The trial lasted for 60 d. We found that body weight increased slightly
      while feed conversion ratio decreased in the CLS-treated group compared with the
      control groups. The total number of aerobic bacteria counted in the intestine of
      carp fed the diet supplemented with the CLS (i.e. Vibrio sp. and E. coli), was
      significantly lower (p = 0.05) compared with the control groups and the CTC
      treated fish, while lactobacillus counts were significantly higher (p = 0.05).
      Lactobacilli counts of the intestine increased significantly (p = 0.05). However,
      the microflora of the skin and gill was not affected by the addition of CuSO4,
      silicate, CLS or CTC. The height of the villi in the proximal, mid and distal
      intestine mucosa of the silicate- and CLS-treated groups was found to be longer
      (p = 0.05) compared with the villi of the control or the CTC-treated fish.
      Supplementation with CuSO4 had no effect on the microflora and the intestinal
      morphology (p = 0.05). These results indicate that CLS had an antibacterial
      activity in vivo, which may help protect the intestinal mucosa from invasion of
      pathogenic bacteria and their toxins.

PMID- 19750813
TI  - Turbellarian black spot disease in bluespine unicornfish Naso unicornis in New
      Caledonia, caused by the parasitic turbellarian Piscinquilinus sp.
AB  - Turbellarian black spot disease is described in a bluespine unicornfish Naso
      unicornis (Perciformes, Acanthuridae) collected from the wild off Noumea, New
      Caledonia, South Pacific. Each cyst contained a whitish worm, 2 to 4 mm in
      length, which was able to swim freely in seawater. Cyst walls consisted of
      fibrous tissue with a scattering of melanocytes. Worms had 2 eyespots at the
      anterior end, a pharynx at the posterior end and a largely undeveloped
      reproductive system. They were identified as Piscinquilinus sp. (= Ichthyophaga
      sp.), a genostomatid turbellarian. The disease spread within 2 wk from a single
      infected fish to 3 other unicornfish in the same tank, in spite of copper
      sulphate and diluted seawater treatment; however, other fish from several
      families kept in the same tank were not infected, suggesting specificity of these
      parasites. Praziquantel injections into the infected fish eliminated the
      infection. Other cases of turbellarian infections are reported from 7 fish
      species off New Caledonia; prevalence is very low (0.3%).

PMID- 19750814
TI  - Finding my way home...

PMID- 19750815
TI  - Change? Who can believe in?

PMID- 19750816
TI  - Unintentional motor vehicle-train collisions--Oklahoma, 1995-2003.
AB  - BACKGROUND: Rates of persons injured in motor vehicle (MV)-train collisions in
      the state of Oklahoma (1.13/100,000 population) are more than 2 times the United
      States rate (0.51/100,000 population). METHODS: To better understand and describe
      unintentional MV-train collisions in Oklahoma, we collected information on MV
      train collisions during 1995-2003 from the United States Federal Railroad
      Administration and from statewide medical examiner reports. Intersections were
      classified into train-activated gates, train-activated flashing lights, and
      passive signage (crossbucks or stop signs). For each type of intersection, MV
      train collisions were calculated as the average annual number of
      collisions/1,000,000 vehicles/100,000 trains. RESULTS: A total of 444
      unintentional MV-train collisions occurred; 48% had at least one injury. The
      average annual intersection collision rate with passive signage (5.15) was eight
      and 37 times, respectively, the rate of train-activated lights (0.63) and train
      activated gates (0.14). Of drivers involved in collisions at intersections with
      gates, 83% ignored the gate warning. Twenty-five percent of drivers were aged <
      25 years, compared with 16% of registered drivers in Oklahoma (p = 0.0001); 74%
      of drivers were male, compared with 49% of registered drivers in Oklahoma (p <
      0.0001). Of fatalities tested for the presence of alcohol, 22% were legally
      intoxicated. CONCLUSIONS: Increasing the number of intersections with active
      warnings and instituting structural changes (i.e., gates that close across both
      lanes of traffic) would likely reduce the number of MV-train collisions in
      Oklahoma and throughout the U.S.

PMID- 19750817
TI  - A sixty-five-year-old female with pneumonia, endocarditis and meningitis.

PMID- 19750818
TI  - Part five: The role of narrative in the everyday practice of medicine medical
      ethics and narrative.

PMID- 19750819
TI  - Here's a second opinion.

PMID- 19750820
TI  - Pharmacy lock-in program promotes appropriate use of resources.

PMID- 19750821
TI  - [Serological characteristics of hantaviruses from clinical specimens analyzed in
      1998-2008 in the Department of Virology, Public Health Institute, Ostrava].
AB  - In 1998 - 2008, serum samples from 464 patients, predominantly residents of the
      Moravia-Silesian Region, were examined in the Department of Virology, Public
      Health Institute in Ostrava, using Enzyme-Linked ImmunoSorbent Assay (ELISA) for
      the detection of specific anti-hantavirus antibodies. Seropositivity was
      ascertained in 41 persons (8.8%). More patients tested seropositive against
      Hantaan virus (24, i.e. 58.5%) than against Puumala virus (13, i.e. 31.7%). Four
      persons were reactive against both antigens. Clinical symptoms corresponding to
      hantavirus infection were observed in 19 seropositive patients. Fifteen of them
      had antibodies reactive with Hantaan virus antigen (cross-reactive with anti
      Dobrava virus), 3 patients had antibodies against Puumala virus and 1 patient had
      both types of antibodies. Clinical data on the other seropositive persons were
      lacking. The higher rate of Dobrava virus infections in the Moravian-Silesian
      Region seems to be associated, among others, with the geographic distribution of
      striped field mouse (Apodemus agrarius) which is the main reservoir of Dobrava
      virus in Central Europe.

PMID- 19750822
TI  - Norwegian scabies in immunosuppressed patient misdiagnosed as an adverse drug
      reaction.
AB  - BACKGROUND: Norwegian or crusted scabies is considered a rare affection and
      presumably represents an abnormal host immune response to Sarcoptes scabiei. As
      the condition mimics a range of dermatoses, it can be easily misdiagnosed and
      mismanaged. CASE REPORT: A 85-year-old woman suffering from bullous pemphigoid
      was referred for evaluation with presumptive diagnosis of an adverse drug
      reaction to hydrochlorothiazide or lacipil. Systemic corticosteroid therapy as
      the mainstay in the control of the bullous skin disorder was increased, but the
      skin condition worsened. ELISA for the detection of antibodies against the drugs
      suspected of causing hypersensitivity was negative. Histological examination
      disclosed inflammatory cells in the upper dermis and parasites. Direct microscopy
      of the scraped material revealed numerous parasites of the Sarcoptes scabiei
      type. The patient was treated with topical keratolytics following traditional
      scabicides for twice as long in comparison with the standard protocol.
      CONCLUSION: Norwegian scabies may be misdiagnosed and mismanaged in
      immunosuppressed patients. The diagnosis of scabies should always be considered
      in immunosuppressed patients with pruritus.

PMID- 19750823
TI  - [Waterborne diseases outbreaks in the Czech Republic, 1995-2005].
AB  - Despite considerable advances in drinking water safety assurance and adherence to
      the public health standards, waterborne diaseases outbreaks have still been
      observed even in industrialized countries. The study objective was to map such
      outbreaks in the Czech Republic in 1995-2005. In this study, an outbreak is the
      occurrence of more cases of disease than normally expected within a specific
      place over a given period of time and a waterborne disease is a disease where
      water is the vehicle or source of infection. The data on waterborne outbreaks was
      obtained from the EPIDAT database (national infectious diseases reporting system)
      information provided by epidemiologists of all regional public health authorities
      and the National Reference Laboratory for Legionella. In 1995 - 2005, 33
      outbreaks with water indicated as the route of transmission were recorded in the
      Czech Republic. The leading cause was unsafe drinking water (27 outbreaks),
      mainly from wells (19 outbreaks); nevertheless, the most serious consequences
      were observed in two outbreaks caused by microbiologically contaminated hot
      water. Other sources of waterborne infection were mineral water springs, a
      swimming pool and a brook. The total of reported cases of waterborne diseases was
      1655, 356 hospitalisations and ten deaths due to legionellosis were recorded. The
      highest number of outbreaks (7) as well as the highest number of cases (841) were
      reported in 1997. Comparison of two five-year periods, i.e. 1996-2000 and 2001
      2005, showed a nearly one third decrease in the total of outbreaks and a half
      reduction in the total of cases in the latter. In view of the limited length of
      monitoring, it is not possible to say with certainty whether it is a random
      distribution or an actual trend. Almost two thirds of cases were diagnosed as
      acute gastroenteritis of probable infectious origin and other frequent waterborne
      diseases were viral hepatitis A and bacillary dysentery. When analyzing the
      described outbreaks, it should be taken into account that only the diagnosed and
      reported outbreak cases are covered, while the actual number of cases is likely
      to be underreported. Although no evidence is available that any vast and serious
      waterborne diseases outbreaks escaped reporting, some small and less serious
      outbreaks may have occurred unnoticed. In the future, the diagnosis,
      investigation and evaluation of waterborne diseases outbreaks should be improved,
      among others by implementing an evidence-based classification system and issuing
      regular surveys of outbreaks and their causes which would be helpful in
      preventing failures in other similar water sources.

PMID- 19750824
TI  - [Use of PCR in diagnosis of enteroviral infections].
AB  - Enteroviruses belonging to the family Picornaviridae are important human
      pathogens. Although most cases of infection caused by these viruses are
      asymptomatic, a wide range of clinical syndromes is observed in manifest cases.
      Conventional laboratory diagnostic methods based on virus isolation and
      identification, or on the detection of specific antiviral antibodies, are costly
      and time consuming. Therefore, they are of little benefit to treatment. We have
      implemented a commercially available PCR-based test for the detection of
      enteroviral infections. In 2008, we analyzed biological specimens from 125
      patients with suspected enteroviral disease, most often involving the nervous
      system. The presence of enterovirus was detected in 39 patients. The results were
      compared with those obtained by the conventional methods. PCR appeared to be a
      valuable method for rapid, accurate and reliable diagnosis of enteroviral
      infections which is of major benefit to patient management.

PMID- 19750825
TI  - [Apitherapy--the role of honey in the chronic wound healing process].
AB  - With increasing frequency, modern medicine directs attention to natural products
      and biological therapy methods and their use in clinical practice. Bee honey as
      well as other bee products (propolis, royal jelly and venom) have already found
      use in medicine not only as immune system stimulants but also as chronic wound
      healing promoters. The major arguments for implementing apitherapy are the low
      cost in comparison with conventional therapies and the fact that honey has proved
      effective against resistant hospital pathogens. Besides antimicrobial
      characteristics associated with no antimicrobial resistance risk, honey has anti
      inflammatory effects. Controlled clinical trials have shown honey to be effective
      in chronic wound healing and gave rise to medihoney. Nevertheless, further study
      is needed to confirm the efficacy and safety of honey in clinical practice.

PMID- 19750827
TI  - [Endophtalmitis after injury with intraocular foreign body in posterior segment
      of the eye].
AB  - OBJECTIVE: To evaluate morphological and functional results of therapy in
      patients with endophthalmitis associated with intraocular foreign bodies in
      posterior segment in retrospective study. MATERIAL AND METHODS: In the Department
      of Ophthalmology, School of Medicine, Comenius University Bratislava we treated
      216 patients (216 eyes) with intraocular foreign bodies in posterior segment of
      the eye in the years 1989-2007. Endophthalmitis developed in 34 eyes (15.7%).
      Patients were in age between 7-59 years, average 35.6 years. Patients were
      examined in outpatient department, follow up ranged from 1 month to 5.6 years,
      average 1.6 years. We evaluated epidemiological factors, morphological and
      functional results in this study. RESULTS: Good morphological results were
      achieved in 18 patients (52.9%) and bad morphological results in 16 patients
      (47.1%). Enucleation, evisceration of the globe, phthisis and retinal detachment
      were defined as bad morphological results. Initial visual acuity 5/50 and better
      had 4 patients (11.8%), less than 5/50 and better than hand movement had 4
      patients (11.8%) and hand movement and less had 26 patients (76.5%). Final visual
      acuity 5/50 and better had 8 patients (23.5%), less 5/50 and better than hand
      movement had 4 patients (11.8%) and hand movement and less had 22 patients
      (64.7%). CONCLUSION: Early recognition and correct treatment of posttraumatic
      endophthalmitis is necessary for maintaining of the eye and its functions.
      Initial visual acuity better than hand movement is a good prognostic factor.

PMID- 19750828
TI  - [Retinal and macular changes after surgical treatment of retinal detachment].
AB  - Retinal detachment represents threat not for visual acuity only, but also for
      visual functions at all. Successful surgery with reattachment of the detached
      retina is the base for the morphological revitalization with possible recovery of
      the retinal function. Specific changes developing during the retinal detachment
      are in detail analyzed using the latest technology and used as the base for
      selection of the most suitable surgical technique. Care should be also given to
      the retinal and macular changes in postoperative management of retinal detachment
      surgery.

PMID- 19750829
TI  - [Functional integrity of neural retina in 2. type diabetics].
AB  - The purpose of this prospective longitudinal study was to investigate early
      defects in functional integrity of neural retina in 2. type diabetic patients
      without or with mild diabetic retinopathy (DR) since there is an evidence of
      early functional changes in neural retina before occurrence of clinical
      manifestation of DR. Psychophysical test of contrast sensitivity (CS) was used
      for the detection of these changes. Relation between CS and systemic risk factors
      (HbAlc, blood pressure (BP), serum lipids and BMI) were also evaluated during a
      follow-up time. There were 48 recent diabetics without DR included in this study
      that were examined 3 times and compared to 23 diabetics with mild DR. The CS
      tests were performed using both Sine Wave Contrast Test (SWCT) and Pelli-Robson
      (PR) test. The reference values for CS threshold were derived from a CS of a
      control group of 52 healthy individuals. Abnormal CS ascertained by both methods,
      SWCT and PR, was observed in diabetics with mild NPDR. In comparison to the
      control group, there was a statistically significant difference of CS in spatial
      frequencies (SF) of 1.5, 6, 12, 18 cycles per degree (cy/deg). In comparison to
      diabetics without DR there was a significant difference of CS in SF of 6, 12 and
      18 cy/deg in diabetics with mild NPDR. Abnormal CS was noticed in 47.8% (SWCT) or
      21.7% (PR) of diabetics with DR. Statistically significant influence of high
      systolic BP on CS values and visual acuity was noticed. There were no
      abnormalities in CS in patients without DR comparing to control group during the
      whole follow-up. However, there was an improvement of CS in SF of 18 cy/deg
      observed between 1. and 3. evaluation of CS. Interaction of change in values of
      HbAlc and total cholesterol to HDL ratio had significant influence on CS
      improvement. Diabetics without DR had significantly better diabetes and blood
      pressure control in comparison to the diabetics with DR. In conclusion, it was
      not proved in this study that CS test is suitable for the screening for DR or
      early functional defects in neural retina before clinical manifestation of DR.
      Early diagnosis of DM and good compensation of diabetes, blood pressure and serum
      lipids level can postpone the onset of DR as well as the visual functions
      impairments.

PMID- 19750830
TI  - [Malignant masquerade syndromes].
AB  - PURPOSE: To evaluate our experience with the diagnosis and treatment of malignant
      masquerade syndromes. METHODS: A retrospective study of 46 patients treated for
      malignant masquerade syndromes at our Department for Diagnosis and Treatment of
      Uveitis, 1st Faculty of Medicine in Prague, between 1995 and 2008, was performed.
      RESULTS: Eighty-nine patients with masquerade syndromes (7.2%) from all 1233
      patients with uveitis were included. Malignant masquerade syndromes were
      recognized in 46 patients (22 females and 24 males, mean age 55 years). The most
      frequent cause of malignant masquerade syndromes was intraocular non-Hodgkin
      lymphoma (26 patients). The primary diagnosis was idiopathic uveitis in many
      cases. The most valuable diagnostic procedure was analysis of intraocular fluids.
      CONCLUSION: Diagnosis of masquerade syndromes should be considered in all
      patients with idiopathic corticosteroid-resistant chronic uveitis. Timely
      diagnosis and treatment may in case of malignant masquerade syndromes improve
      prognosis and sometimes gain control over this potentially lethal disease.

PMID- 19750831
TI  - [Influence AquaLase at corneal endothelial cells].
AB  - PURPOSE: To assess the effect of the cleaning of the posterior capsule using
      pulses of balanced salt solution (BSS) on the corneal endothelial cells. METHODS:
      This pilot study involves 43 patients with bilateral cataracts having lens
      removal using torsional phacoemulsification (Ozil, Infiniti, Alcon) and bimanul
      irrigation/aspiration (I/A). Posterior capsule of the right eye of each patient
      was cleaned using pulses of BSS (AquaLase, Infiniti, Alcon). Surgery was
      performed by one of 2 surgeons (NJ, PR), both eyes of each patient was operated
      on by the same surgeon. Best corrected visual acuity (BCVA), endotelial cell
      count and pachymetry were evaluated pre- and postoperatively as well as occurence
      af peri- and postoperative complications. RESULTS: Preoperative mean pachymetry
      (P) was 566 +/- 45 microm in the right eye (RE) and 562 +/- 42 microm in the left
      eye (LE), mean endotelial cell count (ECC) 2541 +/- 317 cells/mm2 (RE) and 2567
      +/- 311 cells/mm2 (LE). Three months after surgery P was 557 +/- 43 microm (RE)
      and 558 +/- 45 microm (LE) and ECC 2368 +/- 416 cells/mm2 (RE) and 2396 +/- 417
      cells/mm2 (LE). There was no statistical difference in postoperative changes of
      both corneal parameters between right and left eyes. Best corrected visual acuity
      improved in all eyes and no peri-or postoperative complications occured.
      CONCLUSIONS: Cleaning of the posterior capsule using AquaLase is safe for corneal
      endothelial cells.

PMID- 19750832
TI  - [Comparison of contact and immersion techniques of ultrasound biometry in terms
      of target postoperative refraction].
AB  - The success of cataract surgery in terms of the postoperative refractive result
      depends on the calculation of optimal intraocular lens (IOL) power. The accuracy
      of preoperative measurements (keratometry, biometry) is of a great importance due
      to the increasing patients' demands on final refractive results. The purpose of
      this study was to compare the accuracy of contact and immersion techniques of A -
      scan ultrasound biometry in terms of target postoperative refraction while using
      the SRK/T formula. The accuracy of the applied biometric techniques was compared
      by means of the postoperative spherical equivalent (SE). The prospective
      longitudinal study included 111 non-paired eyes, and the preoperative biometry
      was performed by means of an OcuScan ultrasound machine (Alcon).The contact
      technique was used in 48 eyes whereas the immersion technique was employed in 63
      eyes.The mean SE in the group measured by the contact technique was -0.13 D,
      compared to 0.25 D in the group with the applied immersion technique. No
      statistically significant difference was found in postoperative spherical
      equivalents while using both biometric techniques (p > 0.1). In this study the
      choice of a biometric technique had therefore no influence on the predicted
      postoperative refraction. The results have indicated that the biometric
      techniques (contact and immersion) are interchangeable in terms of postoperative
      refractive results.

PMID- 19750834
TI  - [What are the current tasks in the surgical intensive care?].

PMID- 19750833
TI  - [Oclusion of upper ophthalmic vein--a case report].
AB  - Thrombosis of upper ophthalmic vein is both rare and serious pathologic event.
      Authors present a case of isolated unilateral upper ophthalmic vein thrombosis in
      76-year-old woman, who despite treatment ended with amaurosis and secondary
      neovascular glaucoma. In differential diagnosis authors focused on searching for
      inflammatory process of orbit with adjacent structures as well as local and
      general causes leading to venous thrombosis. None of these were proven; it was a
      rare case of a patient with isolated upper ophthalmic vein thrombosis.

PMID- 19750835
TI  - [Infrarenal aortic graft infection].
AB  - INTRODUCTION: The incidence of vascular replacement infection is reported between
      0.5-6.0%. The infection of aortal valve replacement is usually managed by its
      removal and axilofemoral reconstruction. Replacement removal and reconstruction
      in situ is another alternative. The aim of our work is to give the comparison of
      the results obtained with the extra-anatomic reconstruction and alternative
      techniques. MATERIALS AND METHODS: Between January 1987 and August 2008 1324
      abdominal aortal replacements were performed in our department. In 14 patients
      (1.05%) the infection of the replacement occurred; one of the patients was
      operated on in another hospital. In eight patients axilobifemoral/axilopoplietal
      by-pass was applied (Group A). In two patients the whole replacement was removed
      together with in situ reconstruction (ISR) using a new bifurcation replacement.
      In two patients a partial resection of the replacement and the resected part
      substitution or femoro-femoral cross-over by-pass was performed. Three patients
      were treated with a total or partial replacement removal without the following
      reconstruction. RESULTS: In Group A no haemorrhage from the aortal stub occurred.
      The mean value of surgical management due to the replacement infection was 3.5 (1
      6). For Group B the number was 5 (1-16). In Group B there were three
      reinfections, in Group A none. In both Group A and B one patient died; one thigh
      amputation was necessary in Group A, two in Group B. CONCLUSIONS: The partial or
      total removal of the replacement followed with in situ reconstruction is
      considered a safe and good method solving the infection of the aortal replacement
      in some patients. The results are comparable to those obtained with extra
      anatomic reconstruction that remains the method of choice in patients with
      virulent infections.

PMID- 19750836
TI  - [Perioperative metabolic care in a patient with diabetes--recommendations].
AB  - Diabetes mellitus has become the main metabolic disorder. Correct treatment of a
      diabetic patient during the perioperative period is essential, in order to
      improve the treatment outcomes. A diabetic patient must be throroughly assessed
      prior to his procedure and must be postoperatively observed for any signs of
      cardiovascular complications and wound healing disorders. The author present
      diagnostic criteria, recommendations for perioperative management, as well as
      therapeutic measures in hyperglycemia in non-diabetic patients in critical
      conditions following serious surgical procedures or trauma.

PMID- 19750837
TI  - [Antibiotic prophylaxis in urology].
AB  - Antibiotic prophylaxis is an important measure aimed at reduction of infectious
      complications after urologic procedures. The goal of this prospective study is
      assessment of the efficacy, safety and cost of short-time antibiotic prophylaxis
      before planned urologic surgery. Uncomplicated cystoscopy, urodynamic examination
      and ESWL were performed without antibiotic prophylaxis. Oral quinolones were
      effective in prostate biopsy. In open, laparoscopic or endoscopic surgery
      intravenous prophylaxis by cephalosporins had excellent efficacy. All types of
      prophylaxes were very safe and without adverse effects, and could be applied at
      low economic cost.

PMID- 19750838
TI  - [Distal pancreatic resections: indications, surgical technique, and
      complications].
AB  - INTRODUCTION: Distal pancreatic resections are relatively less frequent surgical
      procedures than duodenopancreatectomies. This is due to lower incidence and later
      onset of lesion symptoms in this part of the pancreas. The aim of our work was to
      evaluate retrospectively the results of distal pancreatic resections performed at
      the Department of Surgery, University Hospital in Hradec Kralove from 1996 to
      2008. METHODS: We retrospectively evaluated the indications, surgical procedure
      (including complications) and the postoperative course. All procedures were done
      through transverse laparotomy. The pancreas was transected sharply with a scalpel
      and the resection line was oversewn. Staplers were not used. All the patients
      were given Sandostatin postoperatively. RESULTS: We performed 51 distal
      pancreatic resections at our department from 1996 to 2008, 40 of which were
      distal pancreatic resections with splenectomy (78%). We performed 149
      duodenopancreatectomies in the same time period. Benign lesions or borderline
      lesions (chronic pancreatitis, benign tumours, borderline tumours) were found in
      67% of the surgical specimens. Malignant tumours were found in 33%, most of which
      were adenocarcinoma. Severe pancreatic fistula developed in two patients (3.9%).
      Two reoperations (3.9%) were necessary due to postoperative complications.
      Postoperative mortality was nil. CONCLUSION: We assume that our technique
      resulted in a relatively low morbidity and zero mortality. However, we used this
      technique in all cases, and therefore cannot compare it to other techniques.

PMID- 19750839
TI  - [Experimental tumor therapy using intratumoral injection of dendritic cells].
AB  - AIM OF STUDY: After the treatment of tumors, we often encounter a minimal
      residual sickness. However, the elimination of these leftover tumor cells is
      crucial for the patient. In the past years one of the most discussed options for
      this treatment is Imunotherapy, mainly by Dendritic cells. Dendritic cells are
      the most efficient cells out of the antigen presenting cell group. METHODS AND
      RESULTS: In the first part of the project, we perfected a technique of inducting
      a tumor on an experimental model. We inducted the tumor by the use of
      Carcinogenic substances or with the help of the Sarkom line imortalized
      fibroblasts. Another important part of the project was perfecting the method for
      the preparation of undeveloped dendritic cells from periphery blood monocytes.
      After these significant procedures were developed and perfected we moved onto the
      main part of the study. The Induction of a tumor by the carcenogenic substances
      Ethylennitrosamin and Phenobarbital was successful only in 20 % of the cases and
      therefore, was unusable for our experiment. We inducted the tumors with the
      Sarkom line method. After the application of dendritic cells into the tumor, a
      decrease in the development of the growth of the tumor was achieved. CONCLUSION:
      Imunotherapy using dendritic cells as a basis for treatment is a perspective
      method for treatment of tumors.

PMID- 19750840
TI  - [Blood loss minimization in liver surgery].
AB  - INTRODUCTION: Liver procedures may be associated with severe blood loss,
      requiring administration of blood products. Severe bleeding prolongs resection
      time and has negative effects on morbidity and mortality rates. Any technique,
      which would reduce blood loss during resection procedures is beneficial for a
      patient, as well as for a surgeon. MATERIAL AND METHODOLOGY: Literature overview
      of the commonest resection techniques and intraoperative care aimed at blood loss
      minimization. Assessment of the author's study group of 183 patients, operated
      during 2004-2008. RESULTS AND CONCLUSION: During the study period, 217 liver
      resections were performed in 183 subjects. The mortality rate was 2.7%, the
      morbidity rate 24.6%. In none of the subjects, surgical revision was required for
      postoperative bleeding. The mean blood loss was 820 ml. When saving surgical
      techniques and modern devices are used, and high quality intraoperative and
      postoperative care is provided, the liver resections can be performed with
      minimum blood loss, resulting in fast reconvalescence and minimal complications.

PMID- 19750841
TI  - [The role of classical surgery in treatment of acute abdomen in oncological
      patients].
AB  - Acute abdomen in patients with malignity may present itself as a first sign, or
      might manifest itself during therapy of diagnosed disease. Clinical picture might
      be modified by age of patients, comorbidity, and side effects of multimodal
      therapy. Authors analyze their group of patients, admitted to their department
      with malignant disease. They found out, that almost half of the patients was
      admitted urgently and had serious comorbidities. In operative therapy classical
      surgery dominated. Authors present in discussion causes of this unsatisfactory
      status, as well as literature references concerning urgent cases in different
      types of malignant diseases.

PMID- 19750842
TI  - [Necrotizing infectious complications in diabetic foot syndrome and their
      solutions].
AB  - BACKGROUND: Diabetic foot syndrome affects an increasing percentage of the
      population as the incidence and prevalence of diabetes increases. In some cases
      of the disease, acute necrotizing infectious complications can be observed to the
      extent that they require acute and extensive surgery debridement, often across
      anatomical structures. Local treatment is always preceded by vascular
      examination, possibly limb revascularization. METHODS: After open necrectomy,
      which frees the patient from infectious focus and necrotic tissue, and which, in
      some cases, is the last resort to preserve the limb's length, there is, in the
      second period (after the acquisition of granulation tissue in the defect), a need
      to close the defect. It is possible to let small areas heal spontaneously through
      epithelialisation from the edges of the wound, however, major defects have to be
      close either operationally with secondary suture or with dermoepidermal skin
      grafting. Secondary suture requires a local shift or additional resection of the
      bone to obtain sufficient material for wound closure. Skin graft respects the
      requirement to preserve the maximum of healthy tissue while not slowing down the
      closure of the wound in large defects. RESULTS: Autotransplantation of secondary
      wound with dermoepidermal skin-graft after the debridement of necrotic tissue was
      performed in 16 patients. The average age was 58 years, the average surface of
      skin-grafting was 100 cm2, the interval between transplantation and debridement
      was on average 21 days and from skin-grafting to the healing, of 62 days. 14
      patients were completely healed; one patient suffers chronic osteomyelitis, and
      another one a smack chronic defect in the periphery of the graft. Transplants
      affecting the plant were localized outside the zone of the foot that bears the
      most of the body's weight. CONCLUSION: Local treatment of infectious
      complications in necrotizing diabetic foot syndrome is important for managing the
      acute condition and preservation of limb function. It is appropriate to
      centralize the treatment to podiatric centers cooperating closely with the
      surgeon specializing on wound healing and diabetic foot.

PMID- 19750843
TI  - [Modern radiotherapy in the complex management of soft tissue and bone sarcomas
      in adults--current overview and the author's experience].
AB  - Soft tissue sarcomas and primary bone tumours constitute very heterogenic group.
      Gold treatment standard is surgery in most of them. Nowadays the combination
      surgery with radiotherapy is preferred, because thanks new radiotherapeutic
      technology is possible to apply very high dose of radiation which necessary for
      local control of these tumours. The goal of our article is to describe new
      possibilities of radiotherapy, including neoadjuvant and adjuvant setting,
      intraoperative radiotherapy, interstitial brachytherapy and the combination with
      surgery. But very important is multidisciplinary cooperation to until recently in
      prognostic bad group of patients, concentration these patients to centers with
      modern technique and clinical experience with treatment of soft tissue sarcomas
      and bone tumours.

PMID- 19750844
TI  - [Complications of IPOM plasty--our experience].
AB  - Laparoscopic IPOM (Intraperitoneal Onlay mesh, method of intraperitoneal
      placement of mesh) hernioplasty, using the artificial mesh and when the method is
      managed sufficiently, has been used mainly for larger ventral hernias either in
      linea alba or more for incisional and Spiegel hernias. IPOM hernioplasty were
      supposed to be the gold standard for these hernioplasties, mainly for their
      rapidity, total view during operation and good recovery after it. There have been
      performed these operations also for inguinal hernias at several Surgical
      departments. There is a lot of studies proving safety of this method. On the
      other hand there exist studies pointing out severe postoperative complications of
      this method. These are both inflammatory and adhesive and they make threat for
      their long-term manifestation after primary operation and also for every next
      abdominal operation. We have had patients with both of these complications in our
      set. Considering this method for hernioplasty, we stopped performing IPOM.

PMID- 19750845
TI  - [Septic shock in a patient with the Fournier gangrene with fatal outcome].
AB  - AIM: The authors present a case of a patient with developed Fournier gangrene and
      septic shock. Fournier gangrene belongs to the group of local non-specific
      infection of soft tissues (NSTI). Its incidence is relatively low, but the
      infection is extraordinary aggressive with a possible lethal end. MATERIAL AND
      METHOD: 39 years old patient with 4 days history of Fournier gangrene's
      development was admitted in irreversible septic shock. The initial APACHE II
      score was 36. The delay in treatment was an important factor in the further
      course of illness with lethal end. RESULTS: Above the mentioned 39 years old
      patient died because of septic shock. The hemorrhagic cystitis was the original
      source of infection with further development of Fournier gangrene according to
      the pathological record. CONCLUSION: We often come across all different kinds of
      stages of sepsis from the MODS to the septic shock for patients with Fournier
      gangrene. Causal treatment should be started early. The local surgical excision
      and wide broad antibiotic administrations are basic treatments in the context of
      other treatment modalities according to the current patient's needs. The adjuvant
      hyperbaric oxygen treatment takes place in patients with Fournier gangrene as
      well and is beneficial. The following factor even worsens the illness prognosis:
      delay in diagnostic, higher age, anorectal origin of infection, the amount of
      organ with dysfunction or failure, diabetes mellitus and significant
      immunodeficiency.

PMID- 19750846
TI  - [The complication of a periproctal abscess--Fournier's gangrene or necrotizing
      fasciitis? A case report].
AB  - INTRODUCTION: Periproctal abscess is a routine diagnosis of everyday surgical
      practice. Fournier's gangrene with progress to the sepsis is one of the most
      serious complication of this disease. CASE REPORT: The authors present a case
      review of fulminant surgical infection run as a Fournier's gangrene and a
      necrotizig fasciitis of a right lower limb and body with the progress of severe
      septic status, which started on the strength of a contusion with formation of a
      periproctal absceding haematoma. A patienthood led to the long-term intensive
      care with a necessity of multiple surgeries and with subsequent rehabilitative
      care. This case is rare by the origin of thus extensive infection of soft tissue
      and its illustration of the heftiness of the patient's treatment with such a
      disease. CONCLUSION: Fournier's gangrene and necrotizing fasciitis are loaded by
      a high-grade of mortality. It is one of the most serious surgical infection,
      which ends by death frequently. The therapy is primarily surgical, but it cannot
      be sufficient without aggressive intensive care of a patient.

PMID- 19750847
TI  - [Nutritional intervention in surgery].
AB  - Perioperative nutritional intervention is an integral component of preoperative
      preperation and postoperative therapeutic strategy in surgical patients with
      undernutrition or in patients at severe nutritional risk. The guidelines based on
      clinical trials highlight the risk groups with benefit of artificial nutrition.
      The guidelines get over a lot of dogma from past decades. The introduction of
      these recommendations into practice reduces postoperative complications mainly in
      patients after major surgery, in patients with polytrauma, or in critically ill
      patients. The emphasis is put on shortening of preoperative starvation and on
      early postoperative enteral or peroral feeding.

PMID- 19750848
TI  - For the sake of your patients, talk to each other!

PMID- 19750849
TI  - Coronary artery bypass surgery in old age group: is age itself a barrier?
AB  - OBJECTIVE: To analyse the data retrospectively and identify risk factors that may
      adversely affect mortality in patients aged seventy years and older with coronary
      artery bypass graft (CABG). METHODS: From Jan 2003 to Oct 2007, 63 consecutive
      patients of 70 years or older underwent primary isolated CABG on cardiopulmonary
      bypass (CPB) in Department of Surgery, Liaquat National Hospital. Forty one (65%)
      were male. The mean age was 72.7 +/- 3 years (range 70 to 81 years).
      Preoperatively 83% were in New York Heart Association (NYHA) class III or IV.
      Left main stem (LMS) lesion (> 70%) was present in 20 (32%). Renal impairment
      (RI) with creatinine more then 2 mg/dl was present in 9 (14%) patients. History
      of prior stroke was present in 7 (11%). Emergency surgery (within 48 hours after
      Myocardial Infarct (MI)) was performed in 33 (52%) patients. RESULTS: The overall
      hospital mortality (30 days) was 9.5%. The mean Parsonet score was 23 +/- 3, and
      10 +/- 3 in those who died or survived respectively. Mean intensive care unit
      stay was 2.3 +/- 0.7 days, mean ward stay was 6 +/- 3 days. Preoperative LMS
      lesion or MI less then 48 hours, poor left ventriculal function, prolonged CPB
      time and post operative stroke were the significant independent predictors of
      operative morality. CONCLUSION: CABG can be performed in a selected elderly
      population. Careful attention to risk factors associated with high mortality can
      be helpful in improving post-operative morality. Age in itself may not be
      responsible for high morality.

PMID- 19750850
TI  - Association of common carotid intimal medial thickness (CCA-IMT) with risk
      factors of atherosclerosis in patients with type 2 diabetes mellitus.
AB  - OBJECTIVE: To determine the association of Common Carotid Intimal Medial
      Thickness (CCA-IMT) with risk factors of atherosclerosis in patients with type 2
      diabetes mellitus. METHODS: This is an observational study carried out in 200
      type 2 diabetic patients. Age, gender, duration of diabetes, history of ischaemic
      heart disease, hypertension and smoking was recorded. Body mass index,
      glycosylated haemoglobin (HbA1c), total cholesterol, triglyceride and high
      density (HDL) cholesterol were determined in all the patients. CCA-IMT
      determination was done by Carotid Doppler Ultrasonography. RESULTS: There were
      120 (60%) males and 80 females (40%). Ages ranged from 28 to 79, mean 59.5 +/-
      9.07 years. IMT on right side ranged from 0.4 mm to 2.4 mm, mean 0.88 mm and on
      left side mean IMT was 0.93 mm, range 0.5 mm to 2.5 mm. Duration of DM and BMI
      were correlated with IMT on both the sides (p < .05), statistically inverse
      correlation was seen with HDL cholesterol (p < .05). No significant correlation
      was seen with other variables. CONCLUSION: Duration of DM, BMI and HDL
      cholesterol were associated with CCA-IMT in patients with type 2 DM. No
      significant association was seen with other risk factors.

PMID- 19750851
TI  - Comparison of nerve conduction studies with diabetic neuropathy symptom score and
      diabetic neuropathy examination score in type-2 diabetics for detection of
      sensorimotor polyneuropathy.
AB  - OBJECTIVE: To compare the nerve conduction studies in clinically undetectable and
      detectable sensorimotor polyneuropathy in type 2 diabetics. METHODS: Diagnosed
      diabetics (n = 60) were divided in two groups. Group 1 (n1 = 30) with clinically
      undetectable and group 2 (n2 = 30) with clinically detectable Diabetic
      Polyneuropathy. Detection of the sensorimotor neuropathy was done according to
      Diabetic Neuropathy Symptom Score and Diabetic Neuropathy Examination scores. The
      simplified nerve conduction studies protocol was followed in recording
      amplitudes, velocities and latencies of minimum two (Sural, Peroneal) and maximum
      six i.e. three sensory (Sural, Ulnar, Median) and three motor (Peroneal, Ulnar,
      Tibial) nerves. RESULTS: The comparisons were done between different parameters
      of nerve conduction studies with the neurological scores in undetectable and
      detectable groups using Pearson's chi square test. The amplitudes, velocities,
      latencies, outcome and grading of neuropathy in nerve conduction studies when
      compared with neurological detection scores showed a significant relation in each
      group regarding evaluation (p = 0.005, p = 0.004, p = 0.05, p = 0.00001, p =
      0.003 respectively). CONCLUSIONS: Diabetic Neuropathy Symptom Score and Diabetic
      Neuropathy Examination Score together can help in prompt evaluation of the
      diabetic sensorimotor polyneuropathy though nerve conduction study is more
      powerful test and can help in diagnosing subclinical cases.

PMID- 19750852
TI  - Negative predictive value of mammography and sonography in mastalgia with
      negative physical findings.
AB  - OBJECTIVE: To determine the negative predictive value of mammography and
      sonography in patients with focal/ diffuse breast pain with negative physical
      examination of the breasts. METHODS: A descriptive study, conducted at Radiology
      Department ofAga Khan University Hospital from 2006-2007 for a period of 2 years.
      A total of 207 women were referred for mammography and sonography because of
      focal or diffuse breast pain. Complete follow-up was available only in 55
      patients. The outcome or gold standard was mammograms or ultrasound after an
      average follow-up period of 18 months with negative/benign findings or
      histopathology of the suspicious lesion or imaging which was the gold standard to
      determine the negative predictive value. RESULTS: Out of 55 patients, 17 (31%)
      had negative findings, benign findings were reported in 34 patients (62%), and 4
      (7%) patients were subjected to mammographically guided breast biopsy. All the
      biopsies were done on the basis of abnormal findings on mammograms. All of the 4
      patients had no evidence of cancer on subsequent histopathology. The negative
      predictive value of mammography and ultrasound in women with focal or diffuse
      breast pain was 100%. CONCLUSION: Breast imaging using mammography and/or
      sonography in women who present with local or diffuse breast pain is of
      significant value, to reassure the patient as well as the clinician. However if
      imaging findings are suggestive of pathology a biopsy should not be delayed.

PMID- 19750853
TI  - Bacterial vaginosis.
AB  - OBJECTIVE: To estimate the frequency of bacterial vaginosis in women with preterm
      labour. METHODS: Descriptive cross sectional study carried out in department of
      Obstetrics and Gynaecology, Military Hospital and Army Medical College
      Laboratory, Rawalpindi. Non-probability convenience sampling was used and the
      study was completed in 12 months (from 1st January 2007 - 1st January 2008).
      Hundred patients in preterm labour were included in the study. An objective
      diagnosis of the type of discharge was made. The vaginal pH of the discharge was
      measured. Samples for bacterial culture were obtained. A wet smear of the vaginal
      secretions was made and examined under the microscope for clue cells followed by
      Whiff test. All information was recorded on a specially designed proforma and the
      frequency of patients with bacterial vaginosis was estimated. RESULTS: A
      diagnosis of bacterial vaginosis was made in 21% of the patients by the Amsels
      criteria. However, culture report suggested bacterial vaginosis in 18% of cases
      with most of the cases (56%) having normal flora. Overall, incidence of infection
      was 44% in patients with preterm labour. CONCLUSION: The frequency of bacterial
      vaginosis in our study was found to be 21% in preterm labour

PMID- 19750854
TI  - Evaluation of laparoscopic appendectomy vs. open appendectomy: a retrospective
      study at Aga Khan University Hospital, Karachi, Pakistan.
AB  - OBJECTIVE: To compare open and laparoscopic appendectomies and to evaluate the
      level of efficacy of both types of appendectomy performed at Aga Khan University
      Hospital (AKUH). METHODS: Based on this strong study rationale, a clinical audit
      of patient's records was performed to evaluate the significance of this technique
      as a treatment modality. The study population comprised of patients with
      appendicitis admitted in the Department of Surgery from January 2004 to December
      2004. The patients' charts were reviewed to ascertain whether the procedure was
      done as an acute case or as an elective procedure. The predictor variables
      explored in this study were: age, gender, ultrasound and CT focused procedure,
      operative time, post-operative stay, number of hours required for the return of
      bowel function, use of narcotic analgesia and the total hospital bill of the
      respective patients. RESULTS: A total of 49 patients' clinical charts were
      reviewed. Of these, 29 patients had had laparoscopic appendectomies and the
      remaining 20 had open appendectomies. The mean post-operative stay in days was
      relatively shorter for laparoscopic appendectomy (1.97 +/- 2.3) compared to open
      appendectomy (3.1 +/- 1.8). The average time for the return of bowel movement was
      remarkably lesser for laparoscopic appendectomy (10.6 +/- 8.2) hours than open
      appendectomy (21 +/- 13) hours. Two of the independent variables: CT focused (P
      value: 0.01) and operative times in minutes (P-value: 0.06) were found to be
      significantly associated with the types of appendectomy. Hence our study found
      that laparoscopic appendectomy, although relatively expensive, is a safe and
      effective procedure for the removal of appendix over open appendectomy.

PMID- 19750855
TI  - Profile of colonic biopsies in King Abdul Aziz University Hospital, Jeddah.
AB  - OBJECTIVE: To scrutinize all colonic biopsies and document the prevalence and
      pattern of various colonic diseases amongst the patients presenting at a tertiary
      care hospital of Western Saudi Arabia. METHODS: We examined the record of all
      colonic biopsies, processed at Histopathology Department of King Abdul Aziz
      University Hospital; Jeddah from January 2002 to July 2007. RESULTS: The colonic
      biopsies received during the study period were 711. Biopsies showing
      inflammatory, nonspecific/infective and other miscellaneous colonic lesions were
      477. Out of these, 181 patients showed nonspecific colitis, 122 showed ulcerative
      colitis and 15 cases were of Crohn's disease. Of the 107 benign polyps seen, the
      most dominant was adenomatous polyp. Out of 99 malignant cases, 94 showed
      adenocarcinoma. CONCLUSIONS: Among Inflammatory bowel diseases, ulcerative
      colitis is an important disease in our society. Tubular adenomas are the most
      common type of polyps and adenocarcinoma is the most common malignancy of the
      colon.

PMID- 19750856
TI  - Clinico-pathologic study of 70 enucleations.
AB  - OBJECTIVE: To assess patients' history, demographic charactertics, cause for
      enucleation and orbital implant trends. METHODS: A cross-sectional descriptive
      case study of 70 patients who underwent enucleation for various reasons between
      January 2004 to June 2007 at Khyber Institute of Ophthalmic Medical Sciences,
      Hayatabad Medical Complex, Peshawar were reviewed. The patients' history,
      demographic characteristics, cause for enucleation after histopathology and the
      type of orbital implant were analyzed. RESULTS: Seventy eyes of patients who
      underwent enucleation were reviewed. The male patients were 62.85% and female
      37.14%. The most common age group involved was paediatric in 51.42%.
      Retinoblastoma was the most common indication for enucleation in 42.85% of
      children followed by choroidal melanoma in 17.14%, painful blind eye in 11.42%
      and phthisis bulbi in 8.57% in adults. Enucleation with orbital implant was done
      in 45.71%, with dermofat graft in 34.28% and no implant in 20%. The most common
      complication being erosion in 21.87% and excessive discharge in 15.62%.
      CONCLUSIONS: Males were the usual victims. Majority of patients were of
      paediatric age group. The most common indications for enucleation was
      retinoblastoma in children and choroidal melanoma and painful blind eye in
      adults.

PMID- 19750857
TI  - Choice of operative method for management of isolated zygomatic bone fractures;
      evidence based study.
AB  - OBJECTIVE: To evaluate the treatment outcome of different methods for reduction
      and fixation of isolated zygomatic bone fractures using degree of displacement as
      a guide to classify patients into closed and open reduction groups. METHODS: This
      Clinical Trial was conducted at de' Montmorency College of Dentistry/Punjab
      Dental Hospital, Lahore between 21st July 2000 and 30th June 2003. Sixty patients
      with isolated zygomatic bone fractures were assigned to open and closed reduction
      groups of treatment depending on the degree of fracture displacement. Adequacy of
      reduction was evaluated by comparing pre and post operative radiographs.
      Aesthetic outcome was assessed by biometric evaluation. RESULTS: Reduction was
      adequate in all patients except four. In two of four no facial deformity was
      apparent. No patient showed post surgical change in position of reduced zygomatic
      bone. Biometric evaluation revealed acceptable aesthetics and adequate mouth
      opening in all except two patients. CONCLUSION: Our study indicates that
      displacement of 2 mm at any of the fractured site on occipitomental radiographs
      can be successfully used as a criterion to assign patients into open and closed
      reduction groups, for treatment of isolated zygomatic bone fractures.

PMID- 19750858
TI  - Haematological reference values for full-term, healthy, newborns of Karachi,
      Pakistan.
AB  - OBJECTIVE: To establish reference haematological values (complete blood count) in
      healthy full-term newborns of Karachi. METHODS: This is a cross sectional study
      design based on cord blood sample of 404 newborns and their mothers recruited
      from Sindh Government Qatar Hospital, Ziauddin University Hospital gole market
      campus, Sindh Government hospital, Liaquatabad and Chinniot maternity and child
      hospital. Karachi from July 2006 to April 2008. Both mother's and the new born
      baby's blood was collected in EDTA containing tubes and analyzed for different
      haematological parameters. The data entry and analysis was done on computer
      package SPSS (Statistical Packages of Social Sciences) version 12.0. The results
      were given in the text as mean, standard deviation and 95% confidence intervals
      of haematological values (complete blood count). RESULTS: The mean haemoglobin
      was found to be (14.99 +/- 1.47 gm), which is lower than the standard value
      described in literature. However the total WBCs count and platelet count were
      found to be (13.61 +/- 4.23) and (256. 25 +/- 76.54) respectively, which were
      similar to the other studies. CONCLUSION: Our values provide reference range for
      haematological values in healthy newborns of Karachi, for clinical use by our
      physicians.

PMID- 19750859
TI  - Staging of endometrial carcinoma by magnetic resonance imaging: correlation with
      surgery and histopathology.
AB  - OBJECTIVE: To evaluate the accuracy of MRI in staging of endometrial carcinoma,
      and comparison with surgery and histopathological findings. METHODS: A one year
      prospective cross-sectional study was conducted from 10/3/2005 to 31/5/2006, at
      the Radiology department, Aga Khan University Hospital (AKUH) Karachi. Fifty two
      patients with diagnosis of endometrial carcinoma, referred to radiology
      department for preoperative staging by MRI and had undergone surgery were
      included. RESULTS: MRI was found to be 79% sensitive, 85% specific and 80%
      accurate for staging endometrial carcinoma while PPV and NPV were 97% and 66%
      respectively. CONCLUSION: Magnetic resonance imaging is a good, safe, accurate
      and non invasive imaging modality in staging of endometrial carcinoma. It can be
      used as a first line radiological investigation in patients with endometrial
      carcinoma for treatment planning.

PMID- 19750860
TI  - The BCG scar size in asthmatic and non-asthmatic children.
AB  - OBJECTIVE: To compare the BCG size in asthmatic and nonasthmatic children.
      METHODS: The size of BCG scar of two groups of children (the asthmatic group with
      a family history of some allergic disorder like asthma, atopic dermatitis,
      allergic rhinitis or allergic conjunctivitis in the first degree blood relatives
      and the control non asthmatic group with no history of any allergic disorder in
      the child or in the first degree blood relatives) of age 18 to 60 months having
      weight at or above 5th centile and BCG scar on right arm with a history of BCG
      vaccination in the first month of life, coming to a paediatric Clinic at
      Liaqatpur on every Friday and Sunday from October 2007 to July 2008, was measured
      and compared. RESULTS: Total 284 children were included for the study, 142
      children in each group. The diameter of BCG scar was measured. 45.77% asthmatics
      compared to 31.69% nonasthmatics had BCG scar mark < or = 5 mm. The asthmatic
      patients demonstrated a 1.82 times greater risk of presenting a BCG scar diameter
      of < or = 5 mm when compared to the nonasthmatic group (odd ratio: 1.82; P =
      0.0204). The mean (95% CI) diameter of BCG scar was 6.4mm (CI: 6.026082 to
      6.775918 ) in the nonasthmatic group and 5.8mm ( 95% CI: 5.459303 to 6.146297) in
      asthmatic group. The difference was significant ( t test, P = 0.0204).
      CONCLUSION: Asthmatic children have smaller BCG scar as compared to nonasthmatic
      children.

PMID- 19750861
TI  - Care seeking for STI symptoms in Pakistan.
AB  - OBJECTIVE: To estimate the frequency of Sexually Transmitted Infections (STIs)
      among sex workers and drug users in Pakistan. METHODS: Interviews were conducted
      on 3640 sex workers, injection drug users and truckers about STI symptoms within
      the past year and currently and the care they sought for them. RESULTS: Nearly
      half (46%) reported STI symptoms in the past 12 months and 55% went for
      treatment. Most of the care sought was from the private sector and more by IDUs
      and female sex workers. Increasing age or having a genital ulcer predicted care
      seeking. CONCLUSIONS: The results suggest the need to understand the factors
      determining care seeking among members of high risk groups; and emphasizing the
      role of the private health care providers in treatment and control of STIs.

PMID- 19750862
TI  - Self-reported practices of hand hygiene among the trainees of a teaching hospital
      in a resource limited country.
AB  - OBJECTIVE: To determine the compliance of hand hygiene among the trainee
      physicians of a tertiary care teaching hospital; and to identify physicians'
      opinion regarding various obstacles in adhering to the hand hygiene principles.
      METHODS: Cross-sectional survey was conducted among the Interns (House Officers)
      and Post Graduate trainee physicians of a tertiary care teaching hospital in a
      resource limited country. Subjects were consented and selected through non
      probability convenient sampling. A self-administered questionnaire, based on the
      hand hygiene guidelines laid down by the World Health Organization (WHO) was
      used. RESULTS: A total of 211 questionnaires were completed. Only 4.7% of the
      physicians reported to decontaminate their hands before having direct contact
      with their patients. Only 17% claimed to be aware of the WHO recommendations on
      hand hygiene. Majority of subjects considered "lack of sinks, soap, water and
      disposable towel" as a major barrier towards hand hygiene adherence. Overall
      compliance of hand hygiene was found to be 38.8% but it widely varied as a
      function of patient care activity. CONCLUSION: Hand hygiene practices among
      trainee physicians were not in line with WHO recommendations. To make a
      difference, interventions taken to improve awareness alone, won't be sufficient;
      they have to be supported with improving facilities for hand hygiene.

PMID- 19750863
TI  - Acne vulgaris--an update on pathophysiology and treatment.

PMID- 19750864
TI  - Hereditary prothrombin deficiency.
AB  - Hereditary prothrombin deficiency is one of the rare congenital coagulation
      defects. We report a case of 4 months old child who initially presented at 11/2
      month of age with high-grade fever, generalized convulsions and brownish aspirate
      through nasogastric tube, diagnosed and managed as meningitis and sepsis. He was
      readmitted at 4 months of age with bruises over legs. Coagulation profile was
      suggestive of common pathway defect. Further evaluation revealed absent
      prothrombin level while other factors were within normal limits.

PMID- 19750865
TI  - Esophageal polypoidal mass: presentation of an uncommon pleomorphic carcinoma.
AB  - Pleomorphic carcinomas are primary malignant tumours that are known to arise in
      the lungs, pancreas, gall bladder and intestine. A patient with polypoid tumour
      of the esophagus is described in this report. The patient presented with
      dysphagia. Diagnostic and therapeutic intervention required endoscopic evaluation
      and treatment. Benign esophageal tumours are rarely seen and originate from the
      upper third of esophagus. We observed an esophageal tumour which was interpreted
      as spindle cell carcinoma of the esophagus that caused obstruction. We present
      the clinical picture and histopathological findings of the tumour. To our
      knowledge this is the first local report of spindle cell carcinoma occurring in
      the esophagus and describes its endoscopic and histopathological features with
      distinctive biphasic morphology.

PMID- 19750866
TI  - Foreign body or foreign from body--congenital unilateral lobar hypoplasia of
      lung.
AB  - We report a rare case of congenital unilateral hypoplasia of the lung without any
      other anomaly at Aga Khan University Hospital. A 7-month-old male infant
      presented in emergency room with respiratory distress. There was no history of
      cough and wheeze. X-ray revealed left sided non homogenous opacity along with
      right sided hyperinflation. A suspicion of foreign body was made on chest X-ray
      but bronchoscopy was deferred in view of bilateral equal air entry and absence of
      wheeze. CT scan showed left upper lobe hypoplasia. Child recovered with
      supportive therapy and was discharged home. To the best of our knowledge
      unilateral lobar malformation of the lung is an extremely rare entity and few
      cases have been reported so far.

PMID- 19750867
TI  - Classic virilizing congenital adrenal hyperplasia presenting late: case series
      from Pakistan.
AB  - Deficiency of 21 hydroxylase enzyme deficiency (21OH) activity accounts for 90%
      cases of congenital adrenal hyperplasia (CAH). This results in deficient
      cortisol, increased ACTH, adrenal hyperplasia and increased adrenal androgen
      secretion. There is marked virilization in genetic females which is the hallmark
      of this disorder. Genetic heterogeneity in 21 OHD is well recognized, and both
      severe and mild forms occur. We present three cases of adult females with the
      disease from a larger study to establish genotype, phenotype correlation of
      Pakistani patients with congenital adrenal hyperplasia (CAH) and to highlight
      issues such as diagnostic delay, inappropriate gender assignment at birth, and
      high degree of consanguinity among parents, psychosexual outcome of 21 OHD
      females and the need to develop expertise for early case detection. The analysis
      was done using Amplification Refractory Mutation System (ARMS) PCR. These cases
      show that CAH frequently remains undiagnosed during the newborn period in our
      population due to lack of awareness in the society and lack of proper diagnosis
      by the primary physician. There is a need to develop expertise for early case
      detection.

PMID- 19750868
TI  - The status of serum procalcitonin in pulmonary tuberculosis and nontuberculosis
      pulmonary disease.
AB  - Procalcitonin (PCT) is a marker of the inflammatory response to infection. In the
      present study the serum PCT of 46 pulmonary tuberculosis patients, 46 non
      tuberculosis pulmonary disease and 46 healthy subjects were analyzed using
      semiquantitative PCT-Q kit. All healthy individuals (100%) were negative
      regarding PCT. Using cut-off value of 0.5 ng/ml, The sensitivity, specificity
      positive predictive value and negative predictive value for serum PCT in
      distinguishing tuberculous from nontuberculous pulmonary disease were 36.9%,
      63.1%, 50% and 50%, respectively. According to our results the serum PCT is not a
      reliable marker for diagnosis of pulmonary tuberculosis due to low sensitivity
      and specificity.

PMID- 19750869
TI  - Chinese coal mines--the industrial death trap.

PMID- 19750870
TI  - Knowledge and practice of healthy lifestyle and dietary habits in medical and non
      medical students of Karachi, Pakistan.
AB  - OBJECTIVE: To objectively compare the differences in knowledge and practices
      regarding healthy lifestyle among medical and non-medical students of Karachi
      along with assessment of any perceived barriers. METHODS: This cross-sectional
      study included 350 students between ages 17-24 years from 6 private universities
      of Karachi--three medical and three non-medical Institutions. A self-reported
      questionnaire was employed to assess attitude and barriers to healthy practices
      among the simple random selection of students. RESULTS: On a 10-point scale, the
      average knowledge score of students on general and clinical nutritional knowledge
      was 5.7 +/- 1.51 and 4.4 +/- 1.77, respectively and the difference was
      statistically significant (p < 0.01). Conversely the diet and lifestyle score (85
      point scale) among medical (41.3) and non medical students (40.8) was not
      significant (p = 0.646). There was no difference between the perception of
      medical and non-medical students regarding 'work-related stress' in their life.
      'Lack of time' was cited as the most important reason for skipping meals and as a
      barrier to exercising regularly among both groups. CONCLUSION: The knowledge,
      attitudes and practices of medical students in Karachi suggest that superior
      knowledge about healthy lifestyle does not necessarily result into better
      practices.

PMID- 19750871
TI  - On the move: restless legs syndrome.

PMID- 19750872
TI  - Health practices of health professionals: do doctors practice what they preach?

PMID- 19750873
TI  - Cognitive performance during prismatic displacement as a partial analogue of
      "space fog".
AB  - BACKGROUND: The fact that microgravity adaptation and recovery from the cognitive
      deficit of "space fog" follow approximately the same time course raises the
      possibility that they are related to one another. Two experiments tested this
      hypothesis. METHODS: Because microgravity adaptation is unique to outer space, we
      investigated the Earth-based analogue of adapting to prismatic displacement.
      Participants' goal was to overcome the disruptive effects of this optical
      distortion on the speed and accuracy with which they negotiated an outdoor
      "slalom course." The experimental group had the additional assignment of
      performing a cognitive task. In Experiment 1, the task was making serial
      subtractions of 7 from an initial starting number, while in Experiment 2 it was
      to repeat back a sequence of high- and low-pitched tones. RESULTS: In neither
      experiment did adaptation influence cognitive performance or vice versa. That is,
      the improvement of slalom-walking performance attributable to prism adaptation
      was the same with or without a concurrent cognitive task and cognitive task
      performance was unaffected by exposure to prismatic displacement. Instead, the
      experiments revealed that both prism exposure and cognitive task performance
      reduced participants' walking speed. CONCLUSIONS: These results suggest that the
      pace of astronauts' visual-motor behavior in space will be slowed by both
      microgravity and the cognitive tasks they must perform. They also bolster the use
      of prism adaptation as an inexpensive, ground-based means of studying
      microgravity adaptation.

PMID- 19750874
TI  - Visual field motion effects on the production of manual forces and displacements.
AB  - BACKGROUND: We have previously shown that subjects produce exaggerated arm forces
      when exposed to three times the normal gravitational acceleration (+3 Gz), and
      that this deficit is not related to direct mechanical effects, faulty
      proprioception, or increased cognitive load. Here we investigate whether it is
      related to vestibular activity. METHODS: Novice subjects observed a stationary,
      upward or downward moving visual field while producing pretrained arm forces
      (Exp. A, N = 12) or displacements (Exp. B, N = 12); a control group produced no
      motor responses and their arm EMG was registered (Exp. C, N = 12). RESULTS:
      Produced forces and EMG were higher with the moving than with the stationary
      field, irrespective of field direction (initial force +42%; peak force +20%,
      biceps brachii EMG +21%). Produced displacements were comparable with the moving
      and stationary field. DISCUSSION: The present pattern of findings is similar to
      that yielded previously in +3 Gz, which supports the existence of a common
      underlying mechanism. Specifically, we suggest that +3 Gz and vertical field
      motion stimulate the vestibular system, and that the observed exaggeration of
      produced force is due to vestibular modulation of descending volitional motor
      commands. The fact that displacements were not affected by +3 Gz and moving
      visual fields would then indicate that forces and displacements are controlled
      through distinct pathways which interact differently with the vestibular system.

PMID- 19750875
TI  - Mathematical modeling of the push-pull effect for various acceleration profiles
      and countermeasures.
AB  - BACKGROUND: The push-pull maneuver (PPM) can lead to loss of consciousness in
      pilots of high-performance aircraft. Modeling of the physical and physiological
      aspects of this phenomenon should allow improved countermeasures. METHODS: A
      structurally based mechanistic computer model was developed to incorporate
      dynamic carotid baroreflex responses and detailed modeling of vessel segments for
      different anatomic regions. The model was used to predict the effect of the PPM
      on cardiovascular responses and the protection afforded by extended coverage anti
      G suits (ECGS) and neck pressure. RESULTS: The model was validated by comparing
      the simulation results with previously published experimental data obtained
      during centrifuge and tilt-table studies. Simulations of various PPM acceleration
      profiles indicated that +Gz tolerance was reduced in the presence of higher +Gz
      levels prior to the push phase, more -Gz levels during the push phase, and
      prolongation of the push phase. On the other hand, the onset rate for the two
      phases had only minor effects on +Gz tolerance. Model output suggested that
      improved protection could be provided by an ECGS with minimal inflation delay and
      a multilevel pressure schedule in which the leg bladders inflated to a higher
      pressure than the abdominal bladder. Modeling application of a 100-mmHg neck
      pressure during the push phase partly inactivated the carotid baroreflex, but
      induced only a small increase in tolerance. CONCLUSIONS: Mathematical modeling
      and simulation showed that +Gz tolerance for the PPM might be increased by
      improving the design and inflation schedule of the ECGS.

PMID- 19750876
TI  - Heart rate and autonomic balance during stand tests before and after fighter
      combat missions.
AB  - BACKGROUND: High workload during combat missions is a critical factor in the use
      of modern aircraft. Our objective was to evaluate the impact of piloting in war
      zones on the kinetics of the sympathovagal balance during recovery. METHODS:
      There were 40 military pilots who were monitored during operational flights in
      Afghanistan. Electrocardiographic activity was recorded during stand tests
      performed 1 h before takeoff (T-1), immediately after landing (L+0), 2 h after
      (L+2), and 4 h after (L+4) the flight. Missions were divided in two groups
      according to flight duration. RESULTS: The mean length of long flights was 4:31
      +/- 0:53 h and of short flights 1:27 +/- 0:09 h. For long flights, at L+0, all
      indices related to parasympathetic modulation rose significantly in comparison to
      T-1, L+2, and L+4 (total power L+0: 2083 +/- 414 ms2 x Hz(-1),T-1: 1269 +/- 158
      ms2 x Hz(-1), L+2: 1095 +/- 148 ms2 x Hz(-1), and L+4: 1238 +/- 124 ms2 x Hz(-1);
      high-frequency normalized units (HFnu) L+0: 16 +/- 2%, T-1: 11 +/- 1%, L+2: 10 +/
      1%, and L+4: 11 +/- 1%). At the same time the sympathetic frequency components
      significantly decreased (low-frequency normalized units (LFnu) L+0: 83 +/- 2%, T
      1: 88 +/- 1%, L+2: 90 +/- 1%, and L+4: 89 +/- 1%; LF/HF L+0: 7 +/- 1, T-1: 11 +/-
      1, L+2: 13 +/- 2, and L+4: 16 +/- 3). For short flights, the sympathetic
      components were higher at L+0 (LFnu: 77 +/- 2%; LF/HF: 14 +/- 3) than at T-1
      (LFnu: 66 +/- 5%; LF/HF: 6 +/- 1). A concomitant reduction of vagal components
      was observed. CONCLUSIONS: Modulations of autonomic balance differed with the
      type of mission. A postflight sympathetic increase represents an autonomic
      adaptation due to stress and flight. A raise of parasympathetic modulation after
      flight may be related to the decrease of alertness.

PMID- 19750877
TI  - Aircraft accidents with student pilots flying solo: analysis of 390 cases.
AB  - INTRODUCTION: This study involves an investigation of accidents of student pilots
      flying solo. METHODS: We analyzed NTSB probable cause reports of 390 crashes that
      occurred in the period 2001-2005. RESULTS: The results indicate that despite the
      apparent dangers of unsupervised flights, this type of accident manifests lower
      rates of injuries and fatalities than those found with other types of
      instructional flights. A relatively high number of accidents occurred in the
      landing phase, particularly during the flare maneuver, which confirms earlier
      research on accidents with instructional flights. Compared to all solo pilots,
      student pilots on their first solo flight had a relatively low risk of injury,
      while students with more than 100 h of flight experience had a relatively high
      risk of injury. CONCLUSION: More research is needed into methods for teaching the
      flare maneuver to student pilots. Furthermore, there is an important role for the
      flight instructor in continuing to check on solo flying student pilots, in
      particular when they have accumulated a considerable number of flight hours
      without obtaining a private pilot license and in remedying planning and decision
      making errors by assisting in flight preparations.

PMID- 19750878
TI  - Pain and discomfort in deployed helicopter aviators wearing body armor.
AB  - BACKGROUND: In early 2007, U.S. Army helicopter aviators deployed to Afghanistan
      complained of increased pain frequency during flight. The aviators attributed
      this pain to body armor, which had not been worn prior to deployment. This study
      was conducted to investigate these complaints. METHODS: A retrospective study of
      pain frequency among 68 deployed helicopter aviators was performed using self
      reported categorical pain ratings and flight times abstracted from a safety
      questionnaire. To assess the association of substantial increases in flight time
      on reported pain frequency, study subjects were divided into a group reporting a
      decrease or increase of 1 h or less in average daily flight hours during
      deployment as compared to predeployment (level flight hours, LFH) and a group
      reporting an increase of greater than 1 h in average daily flight hours
      (increased flight hours, IFH). RESULTS: A significantly higher proportion of
      aviators in the IFH group reported an increase in pain frequency as compared to
      LFH (81.5% vs. 61.1%, respectively). The relative risk (RR) of increased pain
      frequency associated with IFH was greatest in the lower back (RR = 1.80), legs
      (RR = 2.60), arms (RR = 9.11), and the groin (RR = 12.1). DISCUSSION: This study
      provides preliminary evidence that complaints of increased pain frequency during
      deployment were associated with substantial increases in flight times. Further
      study is warranted to investigate and confirm the underlying causes of this pain.

PMID- 19750879
TI  - Cataracts in airline pilots: prevalence and aeromedical considerations in Japan.
AB  - INTRODUCTION: Despite modern aviation being increasingly less dependent on human
      factors, the pilot is still part of the aircraft systems and vision is critical
      for flight safety. The incidence of cataract increases with age, but as most
      epidemiological studies focus on senior age groups, there is no data relevant to
      working age groups. PURPOSE: The aim of our study was to elucidate the prevalence
      of lens opacity in Japanese airline pilots. METHODS: A retrospective cohort study
      was conducted at the Japan Aeromedical Research Center. Medical records for all
      ophthalmological assessments performed in the 12-mo period prior to March 2008
      were reviewed. Data collected included whether there was documented lens opacity
      or a history of previous cataract surgery. RESULTS: Over 12 mo, 3780 pilots
      underwent slit-lamp examination with an ophthalmologist as part of their
      scheduled medical and 105 pilots were identified with cataract. Out of these,
      59/105 were bilateral, 29/105 were congenital types (of which 19 were bilateral),
      and 12/105 pilots gave a history of previous cataract surgery. In all 105 pilots,
      the visual acuity was sufficient to continue the privileges of their licenses.
      CONCLUSIONS: This study offers insight into the clinical iceberg of early
      cataracts in persons of working age. Mild and early lens opacities can cause
      significant glare and haze, and changes in color vision, which might compromise
      pilot performance even in the absence of decreased visual acuity. Cataracts in
      otherwise fit pilots have important aeromedical significance which requires
      further consideration.

PMID- 19750880
TI  - Supplemental oxygen effect on hypoxemia at moderate altitude in patients with
      COPD.
AB  - INTRODUCTION: Altitude exposure will cause moderate to severe hypoxemia in
      patients with chronic obstructive pulmonary disease (COPD). Supplemental oxygen
      can be used to attenuate this hypoxemia; however, individual response is variable
      and difficult to predict. The aim of this study was to assess the efficacy of
      oxygen supplementation in patients with COPD at a barometric pressure similar to
      that of a commercial aircraft cabin. METHODS: Following sea-level (40 m) arterial
      blood gases measurements, 18 patients with COPD were driven to altitude (2086 m),
      where blood gases were repeated at rest and while on 2 L x min(-1) of
      supplementary oxygen (altitude O2). RESULTS: Ascent from sea level to altitude
      caused significant hypoxemia (75 +/- 9 vs. 51 +/- 6 mmHg), which was partially
      reversed by supplemental oxygen (64 +/- 9 mmHg). Oxygen supplementation did not
      significantly alter PaCO2 levels (vs. altitude PaCO2). There was a significant
      relationship between the sea-level CaO2 versus the altitude O2 CaO2 (r = 0.89, P
      < 0.001). There was a significant relationship (r = 0.81, P < 0.001) between
      altitude-induced desaturation and resaturation with the administration of oxygen.
      There was a significant negative correlation (r = -0.74, P < 0.001) between
      baseline K(CO) and the improvement in CaO2 with the administration of oxygen.
      CONCLUSION: Low-flow supplemental oxygen during acute altitude exposure will
      partially reverse altitude-induced hypoxemia in patients with COPD. Patients with
      diffusion impairments are likely to experience the greatest altitude
      desaturation, but will gain the most benefit from supplemental oxygen.
      Supplemental oxygen, delivered at 2 L x min(-1), should maintain clinically
      acceptable oxygenation during commercial air travel in patients with COPD.

PMID- 19750881
TI  - Airway intubation in a helicopter cabin: video vs. direct laryngoscopy in
      manikins.
AB  - INTRODUCTION: Airway management may be required during medical evacuation in a
      helicopter when patients deteriorate en route. Laryngoscopist positioning at the
      head of the patient may not be possible, making it difficult to perform direct
      laryngoscopy (DIR). An alternative method is video laryngoscopy (VID) that
      displays magnified images of the glottic opening on a video monitor and allows
      intubation despite nonstandard positioning. METHODS: There were 21 experienced
      aeromedical emergency medical personnel who intubated a recumbent manikin with
      the operator seated at the head of a secured helicopter stretcher in a power-off
      helicopter. Each subject performed intubations using DIR and VID in standard- and
      difficult-airway manikins (STD and DIF, respectively). Data were collected for
      subjective glottic visualization grades, intubation times, and intubation success
      rates. RESULTS: Visualization grades were 2.43 +/- 0.81 for STD-DIR and 1.10 +/-
      0.30 for STD-VID, compared to 1.76 +/- 0.54 for DIF-DIR and 3.72 +/- 0.57 for DIF
      VID. Success rates were 95% for both STD-DIR and STD-VID, 5% for DIF-DIR and 95%
      DIF-VID. Mean intubation time for DIF-VID was 0.90 min +/- 0.80 min, not
      different from STD-DIR. DISCUSSION: The success rate for difficult airway
      intubation by aeromedical personnel in a power-off evacuation helicopter was
      significantly improved by enhancing glottic visualization using VID vs. DIR in a
      manikin.

PMID- 19750882
TI  - Medical certification for pilots of commercial suborbital spaceflights.
AB  - The Aerospace Medical Association convened a Working Group on October 31, 2008,
      with the objective of preparing a position statement on medical certification for
      pilots of commercial suborbital flights. The discussion concerned two areas:
      medical standards and the content of the medical examination. The Working Group
      found that the current medical standards for the Federal Aviation Administration
      Class I certificate were reasonable for crews flying suborbital profiles. It
      further recommended that the medical examination include a history and physical
      examination as well as urinalysis, hemoglobin/hematocrit, hemoglobin A1c, and
      ECG.

PMID- 19750883
TI  - Development of the Facial and Ocular Countermeasures Safety (FOCUS) headform.

PMID- 19750884
TI  - Criteria for design of the mercury environmental control system, method of
      operation and results of manned system operation. Aerosp Med 1961; 32:839-43.

PMID- 19750885
TI  - Changing demography and variable expressivity in autosomal trisomy syndromes.

PMID- 19750886
TI  - Health consequences of nutrition in childhood and early infancy.
AB  - Medical and scientific studies have proven that the body's metabolic programming
      can be influenced by diet and nutrition from early infancy. As a result, the
      incidence and outcome of several metabolic diseases such as obesity, hypertension
      and cardiovascular disorders have been found to be associated with birth weight,
      growth and feeding patterns, and the body composition in early childhood.
      Exclusive or partial breast feeding for at least 6 months is recommended by the
      World Health Organization, while the European Society of Pediatric
      Gastroenterology Hepatology and Nutrition Committee on Nutrition recommends the
      introduction of complementary foods at 4-6 months of age. The fat content of the
      diet should not be below 25% of the energy intake in order to maintain ideal
      growth while dietary proteins above 15% of the energy intake is related to future
      obesity. Long term benefits of breast feeding include a more ideal serum lipid
      profile and blood pressure, improved neuro-cognitive scores, and a decreased
      incidence for atopic dermatitis in children who have family members with atopic
      diseases. Several studies have also acknowledged the long term benefits for neuro
      cognitive development from certain nutrients including long-chain
      polyunstaturated fatty acids and docosahexaenoic acid. Meat intake has proved to
      be beneficial to psychomotor development. It is suggested that early introduction
      for complementary foods before 4 months of age is a risk factor for atopic
      dermatitis; while no strong evidence showed delaying weaning foods can decrease
      the risk for allergic diseases.

PMID- 19750887
TI  - Neonatal and pregnancy outcome in primary antiphospholipid syndrome: a 10-year
      experience in one medical center.
AB  - BACKGROUND: Antiphospholipid syndrome (APS) in pregnancy is characterized by the
      presence of maternal autoantibodies in association with recurrent fetal loss and
      severe obstetric complications such as prematurity, intrauterine growth
      retardation, or placental insufficiency. This study aimed to assess the perinatal
      outcomes in neonates born to mothers with APS. METHODS: The medical records of
      pregnant women with APS and their offspring were retrospectively collected
      between January 1997 and July 2007. Maternal and perinatal histories including
      demographic data, medications, obstetric histories, and neonatal clinical
      manifestations and laboratory data were analyzed. RESULTS: Eleven women with a
      diagnosis of primary APS were included. Eight of these patients had experienced
      frequent spontaneous abortions (72.7%), and four had unexplained fetal deaths
      (36.3%). None of them had vascular thrombosis. Specific autoimmune antibodies
      were detected, including anticardiolipin antibody (n=6), anti-beta2 glycoprotein
      I (n=3), and antiphospholipid antibody (n=7). Among the pregnancies, five had
      preterm births (45.4%), two had intrauterine growth retardation (18.1%), and one
      had intrauterine fetal demise (9.1%). Thrombocytopenia was noted in three babies,
      all of whose mothers had lower platelet counts. One patient with neonatal
      thrombocytopenia developed intracranial hemorrhage, seen on brain images.
      CONCLUSIONS: This limited study suggests that neonates born to mothers with
      primary APS are at risk of prematurity, being small for gestational age, and
      having thrombocytopenia. Further large, prospective studies are required to
      better define the perinatal outcomes.

PMID- 19750888
TI  - Changing clinical presentations and survival pattern in trisomy 18.
AB  - BACKGROUND: The clinical presentations and survival patterns of infants with
      trisomy 18 have changed with increasing utilization of prenatal ultrasound and
      amniocentesis, and improvements in neonatal intensive care. METHODS: We obtained
      data on duration of survival, male to female ratio, and clinical details for
      patients with trisomy 18, and calculated the prevalence rate. RESULTS: We studied
      31 consecutive trisomy 18 infants. The estimated prevalence was 1/4, 144. Eleven
      (35%) were premature infants, and 20 (65%) were full term. Mean birth weight was
      1896 g. Median life expectancy was 12 days; 11 days for males and 14 days for
      females (p = 0.87). The short-term survival rates of 1 week, 4 weeks, and 6
      months were 58%, 32%, and 10%, respectively. The long-term survival rates of 1
      year, 2 years, and 3 years were 6%, 6%, and 3%, respectively. Families signed do
      not-resuscitate consent forms for five male (50%) and 19 female infants (90%) (p
      = 0.043). CONCLUSION: All trisomy 18 infants in this study were preterm or full
      term deliveries. Mean birth weight was lower than previously reported, and a high
      percentage of families signed do-not-resuscitate consent forms. Females did not
      survive longer than males, due to more females not being resuscitated. Most
      infants died in the first few weeks of life, but 3-6% of infants lived for 21
      year. The possibility of long-term survival should be considered when counseling
      parents regarding trisomy 18.

PMID- 19750889
TI  - Balloon angioplasty for native coarctation of the aorta in neonates and infants
      with congestive heart failure.
AB  - BACKGROUND: Balloon angioplasty (BA) is an alternative to surgical repair for
      coarctation of the aorta (CoA) in children. However, its role in the treatment of
      native CoA in neonates and infants remains controversial. The purpose of this
      study was to report the midterm outcomes of BA for native CoA in neonates and
      infants with congestive heart failure (CHF). METHODS: Between July 2000 and March
      2007, 18 neonates and infants with native CoA and CHF who underwent BA were
      enrolled. Patients without recoarctation were designated as group A, while those
      with recoarctation or CHF were designated as group B. The clinical presentations,
      laboratory data, and outcomes were compared between groups. RESULTS: There were
      10 patients in group A and eight in group B. The mean age was 2.8 +/- 3.1 months
      (range, 0.7-11 months). Mean body weight was 4.0 +/- 1.9 kg (range, 2.1-8.0kg).
      CHF improved markedly in all patients immediately after BA, with a reduction in
      systolic pressure gradient from 36.4 +/- 12.0 to 5.6 +/- 6.0 mmHg (p < 0.001).
      The recoarctation rate was 44% (8/18). The risk factors for restenosis were post
      BA systolic pressure gradient >10 mmHg (p = 0.007) and CoA diameter <3 mm (p =
      0.013). CONCLUSIONS: The outcomes of BA for native CoA in neonates and infants
      with CHF remain poor. The incidence of recoarctation is high in neonates and
      patients whose post-BA systolic pressure gradient is >10 mmHg or whose CoA
      diameter is <3 mm.

PMID- 19750890
TI  - Determination of the normal position of the anus in Taiwanese infants.
AB  - BACKGROUND: Anterior displacement of the anus has been reported to be a cause of
      chronic constipation amongst young children. However, the normal position of the
      anus has not been studied in Taiwan. PATIENTS AND METHODS: Normal anal
      positioning was studied in 200 neonates (100 males and 100 females). All of these
      individuals were non-constipated. The position of the anus was numerically
      defined by the anal position index (API), which is the distance from the center
      of the anus to the vagina or scrotum divided by the distance between the vagina
      or scrotum and the coccyx. Thirty non-constipated infants aged between 5 and 19
      months (15 males and 15 females) were included in the study to compare the index
      between neonates and older infants. RESULTS: The API values were 0.54 +/- 0.03
      (95% CI, 0.48-0.60) for newborn males and 0.40 +/- 0.04 (95% CI, 0.32-0.47) for
      newborn females, 0.53 +/- 0.02 (95% CI, 0.49-0.57) for young boys and 0.39 +/-
      0.06 (95% CI, 0.28-0.51) for young girls. The difference in indices between males
      and females was significant, but there was no significant difference in the
      indices between newborns and older infants. CONCLUSIONS: The API is independent
      of age, and provides a constant and reliable parameter for determining the
      position of the anus.

PMID- 19750891
TI  - Clinical manifestations and outcomes of Henoch-Schonlein purpura: comparison
      between adults and children.
AB  - BACKGROUND: Henoch-Schonlein purpura (HSP) primarily affects children, but age at
      onset is thought to be important in determining disease severity and outcome.
      This study compared the clinical and laboratory data from children and adults
      with HSP. METHODS: This retrospective 5-year study enrolled 65 children and 22
      adult HSP patients attending a medical center. RESULTS: Gross hematuria and lower
      extremity edema were significantly more frequent in adults (p < 0.05). All the
      children developed renal involvement within 2 weeks, while 67% of the adult
      patients developed hematuria by the fifth week of disease onset. Elevated white
      blood cell count and increased erythrocyte sedimentation rate were significantly
      more common in children (p < 0.05). Adults had a higher frequency of renal
      involvement (p < 0.05), though this was also present in 14 children (21.54%), 12
      with isolated hematuria and proteinuria and two with nephrotic syndrome. All the
      children maintained normal renal function. Twelve adults had renal involvement
      (52.6%), six with progression to renal insufficiency. Patients with abdominal
      pain at disease onset had a significantly higher probability of developing
      nephrotic syndrome (p < 0.05). Logistic regression revealed that age >20 years,
      male, bloody stools, clinical course with relapse of purpuric rash, and
      persistent rash for >1 month were poor prognostic indicators for HSP nephritis (p
      < 0.05). CONCLUSIONS: HSP nephritis in adults had a higher risk of progression to
      renal insufficiency. More aggressive treatment and extended follow-up with
      repeated urinalysis for at least 6 weeks were often necessary, especially in
      older patients.

PMID- 19750892
TI  - Treatment of duodenal duplication by trans-umbilical exploratory minimal
      laparotomy.
AB  - Duodenal duplication cysts are rare congenital lesions usually diagnosed in
      infancy, although they may present in adulthood. Prenatal diagnosis is difficult,
      and postnatal diagnosis relies on ultrasonography, barium swallow, contrast
      enhanced computerized tomography, magneticresonance imaging (MRI), and magnetic
      resonance cholangiopancreatography. A female newborn was diagnosed with an
      abdominal cyst (size around 6 x 5 x 4 cm) at gestational age (GA) 24 weeks, by
      regular prenatal examination. After her birth at GA 37 weeks, we performed
      abdominal ultrasonography and RI, but there was no definite diagnosis. The usual
      management of an abdominal cyst involves resection by laparotomy (requiring a
      large incision) or laparoscopy (requiring several small incisions). We performed
      an exploratory trans-umbilical minimal laparotomy excision for surgery, and the
      pathology revealed duodenal duplication. In our case, there was no recurrence of
      the cyst after 18 months follow-up, and the operation scar was almost
      undetectable. Trans-umbilical minimal laparotomy excision may be considered as an
      alternative choice for the management of abdominal and duodenal duplication
      cysts.

PMID- 19750893
TI  - Retroperitoneal ganglioneuroma in childhood--a presentation of two cases.
AB  - Ganglioneuromas are considered to be part of the neuroblastoma series of tumors,
      which evolve from the sympathogonia of neural crest origin. As imaging techniques
      have become more widely practiced, the number of ganglioneuromas detected
      incidentally has increased. Preoperative diagnosis of retroperitoneal
      ganglioneuromas is often difficult and the diagnosis is usually based on
      histopathological findings after surgical excision of the tumor. We present two
      cases of this unique disease entity and discuss its clinical presentation,
      therapeutic approach, and clinical outcome.

PMID- 19750894
TI  - Acute torsion of wandering spleen: report of one case.
AB  - Wandering spleen is a rare condition that can lead to splenic infarction or
      rupture if torsion persists. Early diagnosis and intervention are necessary, and
      abdominal ultrasonography and abdominal computed tomography are well accepted as
      the diagnostic imaging modalities. In this study, we present a boy with nic
      infarction due to acute torsion of a wandering spleen, after initial failure to
      demonstrate an ectopic spleen. Instead, acute torsion of the wandering spleen
      with spontaneous partial detorsion was incidentally found by multi-detector row
      CT with angiography. The patient was managed by splenectomy instead of
      splenopexy, because poor reperfusion after Laparoscopic detorsion.

PMID- 19750895
TI  - Economics, altruism and Maslow.

PMID- 19750896
TI  - Pulaski Skyway.

PMID- 19750897
TI  - Oral pathology quiz #63. Case number 1. Central giant cell lesion.

PMID- 19750898
TI  - Oral pathology quiz #63. Case number 2. Squamous cell carcinoma.

PMID- 19750899
TI  - A dental adventure in Southeast Asia.

PMID- 19750900
TI  - An opinion on access.

PMID- 19750902
TI  - The devil and Dr. Brewster.

PMID- 19750901
TI  - Reflections on a few formative patients.

PMID- 19750903
TI  - Clinical documentation improvement. Gauging the need, starting off right.
AB  - There's no down side to better documentation, but many organizations have found
      MS-DRGs and RACs offer the motivation necessary to get their programs started.

PMID- 19750904
TI  - Coding training in England. Greater access to education should aid us coders with
      transition.
AB  - A lack of comprehensive training on ICD-10 and other code sets has contributed to
      data quality issues in England. US coders, looking ahead to their own transition
      to the code set, should be encouraged by their access to a strong coding
      infrastructure.

PMID- 19750905
TI  - Help wanted. Schools struggle placing students in PPEs.
AB  - Well-trained students make well-trained new hires, which is why professional
      practice experiences are an important part of HIM education. However, PPE
      coordinators say it is getting harder to place students in today's hectic
      workplace. Yet the benefits, they say, are there for everyone.

PMID- 19750906
TI  - Managing audit trails.

PMID- 19750907
TI  - CMS's 2009 security assessment process.

PMID- 19750908
TI  - Value-based purchasing. What it means for HIM professionals.

PMID- 19750909
TI  - ARRA FAQs.

PMID- 19750910
TI  - Understanding HACs and SREs for quality reporting and reimbursement.

PMID- 19750911
TI  - New ICD-9-CM diagnosis codes for FY 2010.

PMID- 19750912
TI  - Assigning E codes.

PMID- 19750913
TI  - Channeling HIM skills into a passion.

PMID- 19750914
TI  - Regulation of neuronal activities within REM sleep-sign generators.

PMID- 19750915
TI  - Losing sleep over work? Does it matter?

PMID- 19750916
TI  - Evidence of subthalamic PGO-like waves during REM sleep in humans: a deep brain
      polysomnographic study.
AB  - STUDY OBJECTIVES: The aim of this study was to examine whether the subthalamic
      nucleus (STN) plays a role in the transmission of PGO-like waves during REM sleep
      in humans. DESIGN: Simultaneous recordings from deep brain electrodes to record
      local field potentials (LFPs), and standard polysomnography to ascertain
      sleep/wake states. SETTING: Main Hospital, department of clinical neurophysiology
      sleep laboratory. PARTICIPANTS: 12 individuals with Parkinson's disease, with
      electrodes implanted in the STN; and, as a control for localization purposes, 4
      cluster headache patients with electrodes implanted in the posterior
      hypothalamus. INTERVENTIONS: All subjects underwent functional neurosurgery for
      implantation of deep brain stimulation electrodes. RESULTS: Sharp, polarity
      reversed LFPs were recorded within the STN during REM sleep in humans. These
      subthalamic PGO-like waves (2-3 Hz, 80-200 pV, and 300-500 msec) appeared during
      REM epochs as singlets or in clusters of 3-13 waves. During the pre-REM period,
      subthalamic PGO-like waves were temporally related to drops in the submental
      electromyogram and/or onset of muscular atonia. Clusters of PGO-like waves
      occurred typically before and during the bursts of rapid eye movements and were
      associated with an enhancement in fast (15-35 Hz) subthalamic oscillatory
      activity. CONCLUSION: Subthalamic PGO-like waves can be recorded during pre-REM
      and REM sleep in humans. Our data suggest that the STN may play an active role in
      an ascending activating network implicated in the transmission of PGO waves
      during REM sleep in humans.

PMID- 19750917
TI  - Orexin neurons are necessary for the circadian control of REM sleep.
AB  - STUDY OBJECTIVES: The orexin-producing neurons are hypothesized to be essential
      for the circadian control of sleep/wake behavior, but it remains unknown whether
      these rhythms are mediated by the orexin peptides or by other signaling molecules
      released by these neurons such as glutamate or dynorphin. To determine the roles
      of these neurotransmitters, we examined the circadian rhythms of sleep/wake
      behavior in mice lacking the orexin neurons (ataxin-3 [Atx] mice) and mice
      lacking just the orexin neuropeptides (orexin knockout [KO] mice). DESIGN: We
      instrumented mice for recordings of sleep-wake behavior, locomotor activity
      (LMA), and body temperature (Tb) and recorded behavior after 6 days in constant
      darkness. RESULTS: The amplitude of the rapid eye movement (REM) sleep rhythm was
      substantially reduced in Atx mice but preserved in orexin KO mice. This blunted
      rhythm in Atx mice was caused by an increase in the amount of REM sleep during
      the subjective night (active period) due to more transitions into REM sleep and
      longer REM sleep episodes. In contrast, the circadian variations of Tb, LMA,
      Wake, non-REM sleep, and cataplexy were normal, suggesting that the circadian
      timekeeping system and other output pathways are intact in both Atx and KO mice.
      CONCLUSIONS: These results indicate that the orexin neurons are necessary for the
      circadian suppression of REM sleep. Blunting of the REM sleep rhythm in Atx mice
      but not in orexin KO mice suggests that other signaling molecules such as
      dynorphin or glutamate may act in concert with orexins to suppress REM sleep
      during the active period.

PMID- 19750918
TI  - Cholinergic modulation of GABAergic and glutamatergic transmission in the dorsal
      subcoeruleus: mechanisms for REM sleep control.
AB  - STUDY OBJECTIVES: Dorsal subcoeruleus (SubCD) neurons are thought to promote PGO
      waves and to be modulated by cholinergic afferents during REM sleep. We examined
      the differential effect of the cholinergic agonist carbachol (CAR) on excitatory
      and inhibitory postsynaptic currents (PSCs), and investigated the effects of CAR
      on SubCD neurons during the developmental decrease in REM sleep. DESIGN: Whole
      cell patch clamp recordings were conducted on brainstem slices of 7- to 20-day
      old rats. MEASUREMENTS AND RESULTS: CAR acted directly on 50% of SubCD neurons by
      inducing an inward current, via both nicotinic and muscarinic M1 receptors. CAR
      induced a potassium mediated outward current via activation of M2 muscarinic
      receptors in 43% of SubCD cells. Evoked stimulation established the presence of
      NMDA, AMPA, GABA, and glycinergic PSCs in the SubCD. CAR was found to decrease
      the amplitude of evoked EPSCs in 31 of 34 SubCD cells, but decreased the
      amplitude of evoked IPSCs in only 1 of 13 SubCD cells tested. Spontaneous EPSCs
      were decreased by CAR in 55% of cells recorded, while spontaneous IPSCs were
      increased in 27% of SubCD cells. These findings indicate that CAR exerts a
      predominantly inhibitory role on fast synaptic glutamatergic activity and a
      predominantly excitatory role on fast synaptic GABAergic/glycinergic activity in
      the SubCD. CONCLUSION: We hypothesize that during REM sleep, cholinergic "REM-on"
      neurons that project to the SubCD induce an excitation of inhibitory interneurons
      and inhibition of excitatory events leading to the production of coordinated
      activity in SubCD projection neurons. The coordination of these projection
      neurons may be essential for the production of REM sleep signs such as PGO waves.

PMID- 19750919
TI  - Excessive muscle activity increases over time in idiopathic REM sleep behavior
      disorder.
AB  - STUDY OBJECTIVES: Rapid eye movement (REM) sleep behavior disorder (RBD) is
      characterized by excessive electromyographic (EMG) activity due to dysfunction of
      the brainstem structures modulating REM sleep atonia. Patients with idiopathic
      RBD often develop a neurodegenerative disease, such as Parkinson disease, over
      the years, suggesting progression of an underlying pathologic process in the
      brainstem. It is unknown if the excessive EMG activity in REM sleep changes over
      time in patients with idiopathic RBD. SETTING: University hospital sleep
      disorders center. PARTICIPANTS: Eleven patients with idiopathic RBD who were
      studied at baseline and after a mean follow-up of 5 years. INTERVENTIONS: NA.
      MEASUREMENTS AND RESULTS: Eleven patients with idiopathic RBD underwent
      polysomnography (PSG) at the moment of the diagnosis of RBD (PSG1) and after a
      mean follow-up of 5 years (PSG2). Tonic EMG activity in PSG1 and PSG2 was blindly
      quantified and compared in the mentalis muscle during REM sleep. Phasic EMG
      activity in PSG1 and PSG2 was blindly quantified and compared in the mentalis
      muscle, both biceps brachii, and both anterior tibialis during REM sleep.
      Patients were 9 men and 2 women with a mean age of 73.2 +/- 5.4 years and a mean
      RBD duration of 10.7 +/- 5.3 years at PSG2. In each of the 5 muscles and
      combination of muscles evaluated, phasic EMG activity was significantly greater
      in PSG2 than in PSG1 (P < 0.022 in all muscles studied). Mentalis tonic EMG
      activity increased from 30% to 54% (P = 0.013). No correlation was found between
      age of the patients and quantity of EMG activity at PSG1 (tonic; P = 0.69, phasic
      P = 0.89) and at PSG2 (tonic; P = 0.16, phasic; P = 0.42). CONCLUSION: Excessive
      tonic and phasic EMG activity during REM sleep increases over time in subjects
      with idiopathic RBD. This finding suggests that, in subjects with idiopathic RBD,
      there is an underlying progressive pathologic process damaging the brainstem
      structures that modulate REM sleep.

PMID- 19750920
TI  - Breast cancer patients have progressively impaired sleep-wake activity rhythms
      during chemotherapy.
AB  - PURPOSE: Prior cross-sectional studies have shown that cancer patients have sleep
      wake activity cycles that show little distinction between daytime and nighttime,
      a pattern indicative of circadian disruption. This pattern is seen both before
      and during cancer treatment. Long-term data are needed, however, to assess to
      what extent circadian rhythm impairments evolve over the course of chemotherapy.
      The goal of this study was to assess the longitudinal course of sleep-wake
      activity rhythms before and during chemotherapy for breast cancer. PATIENTS AND
      METHODS: Ninety-five women scheduled to receive neoadjuvant or adjuvant
      anthracycline based chemotherapy for a stage I-III breast cancer participated.
      The participants wore a wrist actigraph for 72 consecutive hours at baseline (pre
      chemotherapy), as well as during the weeks 1, 2 and 3 (W1, W2, W3) of cycle 1 and
      cycle 4 of chemotherapy. Sleep-wake circadian activity variables were computed
      based on actigraphic data. RESULTS: Compared to baseline, with the exception of
      acrophase, all circadian rhythm variables examined, including amplitude, mesor,
      up-mesor, down-mesor, and rhythmicity were significantly impaired during the
      first week of both chemotherapy cycles. Although the circadian variables
      approached baseline values during W2 and W3 of cycle 1, most remained
      significantly more impaired during W2 and W3 of cycle 4. CONCLUSION: These data
      suggest that the first administration of chemotherapy is associated with
      transient disruption of sleep-wake rhythm, while repeated administration of
      chemotherapy results in progressively worse and more enduring impairments in
      sleep-wake activity rhythms.

PMID- 19750921
TI  - Brain activation changes before and after PAP treatment in obstructive sleep
      apnea.
AB  - STUDY OBJECTIVES: Obstructive sleep apnea syndrome (OSAS) is associated with
      cognitive and functional deficits, most of which are corrected after positive
      airway pressure (PAP) treatment. Previous studies investigating the neural
      underpinnings of OSAS failed to provide consistent results both on the cerebral
      substrates underlying cognitive deficits and on the effect of treatment on these
      anomalies. The aims of the study were a) to investigate whether never-treated OSA
      patients demonstrated differences in brain activation compared to healthy
      controls during a cognitive task; and b) to investigate whether any improvements
      in cognitive functioning found in OSA patients after treatment reflected a change
      in the underlying cerebral activity. DESIGN: OSA patients and healthy controls
      underwent functional magnetic resonance imaging (fMRI) scanning. They were
      compared on performance and brain activation during a 2-back working-memory task.
      Patients were also re-evaluated after 3 months treatment with PAP. Cognitive
      functions were evaluated using neurocognitive tests. Sleepiness (ESS), mood (Beck
      Depression Inventory) and, quality-of-life (SF-36) were also assessed. SETTING:
      The Sleep Disorders Center and CERMAC at the Vita-Salute San Raffaele University.
      PATIENTS OR PARTICIPANTS: 17 OSA patients and 15 age- and education-matched
      healthy controls. INTERVENTIONS: PAP treatment for 3 months. MEASUREMENTS AND
      RESULTS: Compared to controls, never-treated OSA patients showed increased
      activations in the left frontal cortex, medial precuneus, and hippocampus, and
      decreased activations in the caudal pons. OSA patients showed decreases in
      activation with treatment in the left inferior frontal gyrus and anterior
      cingulate cortex, and bilaterally in the hippocampus. Most neurocognitive
      domains, impaired at baseline, showed significant improvement after treatment.
      CONCLUSIONS: OSA patients showed an overrecruitment of brain regions compared to
      controls, in the presence of the same level of performance on a working-memory
      task. Decreases of activation in prefrontal and hippocampal structures were
      observed after treatment in comparison to baseline. These findings may reflect a
      neural compensation mechanism in never-treated patients, which is reduced by
      effective treatment.

PMID- 19750922
TI  - Upper airway collapsibility during REM sleep in children with the obstructive
      sleep apnea syndrome.
AB  - STUDY OBJECTIVES: In children, most obstructive events occur during rapid eye
      movement (REM) sleep. We hypothesized that children with the obstructive sleep
      apnea syndrome (OSAS), in contrast to age-matched control subjects, would not
      maintain airflow in the face of an upper airway inspiratory pressure drop during
      REM sleep. DESIGN: During slow wave sleep (SWS) and REM sleep, we measured
      airflow, inspiratory time, inspiratory time/total respiratory cycle time,
      respiratory rate, tidal volume, and minute ventilation at a holding pressure at
      which flow limitation occurred and at 5 cm H2O below the holding pressure in
      children with OSAS and in control subjects. SETTING: Sleep laboratory.
      PARTICIPANTS: Fourteen children with OSAS and 23 normal control subjects.
      RESULTS: In both sleep states, control subjects were able to maintain airflow,
      whereas subjects with OSAS preserved airflow in SWS but had a significant
      decrease in airflow during REM sleep (change in airflow of 18.58 +/- 12.41 mL/s
      for control subjects vs -44.33 +/- 14.09 mL/s for children with OSAS, P = 0.002).
      Although tidal volume decreased, patients with OSAS were able to maintain minute
      ventilation by increasing the respiratory rate and also had an increase in
      inspiratory time and inspiratory time per total respiratory cycle time
      CONCLUSION: Children with OSAS do not maintain airflow in the face of upper
      airway inspiratory-pressure drops during REM sleep, indicating a more collapsible
      upper airway, compared with that of control subjects during REM sleep. However,
      compensatory mechanisms exist to maintain minute ventilation. Local reflexes,
      central control mechanisms, or both reflexes and control mechanisms need to be
      further explored to better understand the pathophysiology of this abnormality and
      the compensation mechanism.

PMID- 19750923
TI  - Sleep duration and obesity in children: is the association dependent on age and
      choice of the outcome parameter?
AB  - STUDY OBJECTIVES: To assess the association between sleep duration in children
      and different markers of body fat by age and weight status. DESIGN: Nation-wide
      health survey. Measurement of BMI and body fat percentage (KFA) calculated from
      weight, height, skin fold thickness, age, and sex. Sleep duration and potential
      confounding variables were assessed in a parent questionnaire. SETTING: N/A.
      PARTICIPANTS: 7767 German resident children from 3 to 10 years of age.
      INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Prolongation of sleep duration from
      the lowest to the highest percentile accounted for a similar mean decrease
      founding variables and did not show a systematic age dependency. The greatest
      effects of sleep duration were seen for the upper tails of the BMI and KFA
      distributions, which were about four as high as the lower tails. CONCLUSIONS: The
      association between sleep duration and weight status is of similar size through
      ages 3 to 10 years. The sleep-associated changes in BMI are likely to be a
      consequence of higher body fat and primarily affect children whose BMI or KFA is
      already elevated. These findings favor hormonal pathways nurturing adipose tissue
      playing a key role in the underlying physiological mechanisms.

PMID- 19750924
TI  - Lucid dreaming: a state of consciousness with features of both waking and non
      lucid dreaming.
AB  - STUDY OBJECTIVES: The goal of the study was to seek physiological correlates of
      lucid dreaming. Lucid dreaming is a dissociated state with aspects of waking and
      dreaming combined in a way so as to suggest a specific alteration in brain
      physiology for which we now present preliminary but intriguing evidence. We show
      that the unusual combination of hallucinatory dream activity and wake-like
      reflective awareness and agentive control experienced in lucid dreams is
      paralleled by significant changes in electrophysiology. DESIGN: 19-channel EEG
      was recorded on up to 5 nights for each participant. Lucid episodes occurred as a
      result of pre-sleep autosuggestion. SETTING: Sleep laboratory of the Neurological
      Clinic, Frankfurt University. PARTICIPANTS: Six student volunteers who had been
      trained to become lucid and to signal lucidity through a pattern of horizontal
      eye movements. MEASUREMENTS AND RESULTS: Results show lucid dreaming to have REM
      like power in frequency bands delta and theta, and higher-than-REM activity in
      the gamma band, the between-states-difference peaking around 40 Hz. Power in the
      40 Hz band is strongest in the frontal and frontolateral region. Overall
      coherence levels are similar in waking and lucid dreaming and significantly
      higher than in REM sleep, throughout the entire frequency spectrum analyzed.
      Regarding specific frequency bands, waking is characterized by high coherence in
      alpha, and lucid dreaming by increased delta and theta band coherence. In lucid
      dreaming, coherence is largest in frontolateral and frontal areas. CONCLUSIONS:
      Our data show that lucid dreaming constitutes a hybrid state of consciousness
      with definable and measurable differences from waking and from REM sleep,
      particularly in frontal areas.

PMID- 19750925
TI  - Does the circadian modulation of dream recall modify with age?
AB  - STUDY OBJECTIVES: The ultradian NREM-REM sleep cycle and the circadian modulation
      of REM sleep sum to generate dreaming. Here we investigated age-related changes
      in dream recall, number of dreams, and emotional domain characteristics of
      dreaming during both NREM and REM sleep. DESIGN: Analysis of dream recall and
      sleep EEG (NREM/REM sleep) during a 40-h multiple nap protocol (150 min of
      wakefulness and 75 min of sleep) under constant routine conditions. SETTING:
      Centre for Chronobiology, Psychiatric Hospital of the University of Basel, Basel,
      Switzerland. PARTICIPANTS: Seventeen young (20-31 years) and 15 older (57-74
      years) healthy volunteers INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Dream
      recall and number of dreams varied significantly across the circadian cycle and
      between age groups, with older subjects exhibiting fewer dreams (P < 0.05),
      particularly after naps scheduled during the biological day, closely associated
      with the circadian rhythm of REM sleep. No significant age differences were
      observed for the emotional domain of dream content. CONCLUSIONS: Since aging was
      associated with attenuated amplitude in the circadian modulation of REM sleep,
      our data suggest that the age-related decrease in dream recall can result from an
      attenuated circadian modulation of REM sleep.

PMID- 19750927
TI  - Insomnia, depression, and physical disorders in late life: a 2-year longitudinal
      community study in Koreans.
AB  - STUDY OBJECTIVES: To investigate prevalence, incidence, and persistence of
      insomnia, and their bidirectional longitudinal associations with depression and
      physical disorders. DESIGN: A community based longitudinal study. SETTING: Elders
      living in private households in South Korea. PARTICIPANTS: 1204 people > or = 65
      years of age were evaluated at baseline; 909 of them (75%) were re-interviewed
      after 2 years. MEASUREMENTS AND RESULTS: Insomnia was defined as difficulty in
      initiation or maintenance of sleep > or = 3 nights per week over the last month.
      Diagnosis of depression (Geriatric Mental State) and number of physical disorders
      were ascertained. Sociodemographic and clinical covariates included age, gender,
      education, housing, past occupation, current employment, living area, life
      events, social deficit, physical activity, cognitive impairment, anxiety, and
      daily drinking. Of those (27%) with insomnia at baseline, 40% had insomnia at
      follow-up. Of those without insomnia at baseline, 23% had insomnia at follow-up.
      Baseline depression was significantly associated with prevalence and incidence of
      insomnia. Baseline number of physical disorders was significantly associated with
      prevalence, incidence, and persistence of insomnia. Baseline insomnia was
      independently associated with incident depression and an increase in reported
      physical disorders. CONCLUSIONS: Insomnia was common and often persistent in this
      population. Insomnia was closely and reciprocally related to depression and
      physical disorders.

PMID- 19750928
TI  - Narcolepsy with long sleep time: a specific entity?
AB  - BACKGROUND: The classical narcolepsy patient reports intense feelings of
      sleepiness (with/out cataplexy), normal or disrupted nighttime sleep, and takes
      short and restorative naps. However, with long-term monitoring, we identified
      some narcoleptics resembling patients with idiopathic hypersomnia. OBJECTIVE: To
      isolate and describe a new subtype of narcolepsy with long sleep time). SETTING:
      University Hospital DESIGN: Controlled, prospective cohort PARTICIPANTS: Out of
      160 narcoleptics newly diagnosed within the past 3 years, 29 (18%) had a long
      sleep time (more than 11 h/24 h). We compared narcoleptics with (n = 23) and
      without (n = 29) long sleep time to 25 hypersomniacs with long sleep time and 20
      healthy subjects. INTERVENTION: Patients and controls underwent face-to face
      interviews, questionnaires, human leukocyte antigen (HLA) genotype, an overnight
      polysomnography, multiple sleep latency tests, and 24-h ad libitum sleep
      monitoring. RESULTS: Narcoleptics with long sleep time had a similar disease
      course and similar frequencies of cataplexy, sleep paralysis, hallucinations,
      multiple sleep onset in REM periods, short mean sleep latencies, and HLA
      DQB1*0602 positivity as narcoleptics with normal sleep time did. However, they
      had longer sleep time during 24 h, and higher sleep efficiency, lower Epworth
      Sleepiness Scale scores, and reported their naps were more often unrefreshing.
      Only 3/23 had core narcolepsy (HLA and cataplexy positive). CONCLUSIONS: The
      subgroup of narcoleptics with a long sleep time comprises 18% of narcoleptics.
      Their symptoms combine the disabilities of both narcolepsy (severe sleepiness)
      and idiopathic hypersomnia (long sleep time and unrefreshing naps). Thus, they
      may constitute a group with multiple arousal system dysfunctions.

PMID- 19750926
TI  - Workplace bullying and sleep disturbances: findings from a large scale cross
      sectional survey in the French working population.
AB  - STUDY OBJECTIVES: The purpose of this study was to explore the associations
      between workplace bullying, the characteristics of workplace bullying, and sleep
      disturbances in a large sample of employees of the French working population.
      DESIGN: Workplace bullying, evaluated using the validated instrument developed by
      Leymann, and sleep disturbances, 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, physical
      and 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. SETTING: General working population.
      PARTICIPANTS: The study population consisted of a random sample of 3132 men and
      4562 women of the working population in the southeast of France. RESULTS:
      Workplace bullying was strongly associated with sleep disturbances. Past exposure
      to bullying also increased the risk for this outcome. The more frequent the
      exposure to bullying, the higher the risk of experiencing sleep disturbances.
      Observing someone else being bullied in the workplace was also associated with
      the outcome. Adjustment for covariates did not modify the results. Additional
      adjustment for self-reported health and depressive symptoms diminished the
      magnitude of the associations that remained significant. CONCLUSIONS: The
      prevalence of workplace bullying (around 10%) was found to be high in this study
      as well was the impact of this major job-related stressor on sleep disturbances.
      Although no conclusion about causality could be drawn from this cross-sectional
      study, the findings suggest that the contribution of workplace bullying to the
      burden of sleep disturbances may be substantial.

PMID- 19750929
TI  - Identification and function of agrin expressed in rat brain microvessels.
AB  - Agrin isoforms in the brain microvessels were investigated. Brain microvessels
      prepared from rat cerebral cortex expressed the short amino terminal (SN)
      isoform, which contains a transmembrane sequence of SN agrin, and the long amino
      terminal (LN) isoform, which contains a signal sequence for secretion of LN
      agrin, were detected in the microvessels. The expression of LN form mRNA in
      comparison with that of SN form was higher in the brain microvessels than in the
      cerebral cortex, indicating preferential expression of LN form agrin in the
      microvessels. In addition, the amino-terminal sequence of agrin expressed in the
      rat brain microvessels was determined by rapid amplification of 5' cDNA end (5'
      RACE). The sequence contained a cluster of hydrophobic amino acids, which may
      form a signal sequence for secretion. Transfection of expression vector coding
      amino-terminal sequence of LN agrin fused with green fluorescence protein (GFP)
      into human embryonic kidney (HEK293) cells caused expression of the protein in
      the cell as well as in the medium, whereas SN agrin fused with GFP expressed at
      the cell surface. These results show that the major form of agrin expressed in
      the brain microvessels is of basal lamina-associated LN agrin and suggest that LN
      agrin may play a role in molecular organization at the interface between the
      parenchyma cells and microvessels.

PMID- 19750930
TI  - Immunomodulating activities in bran extracts of Japanese red, black and brown
      rices.
AB  - To determine the potent immunomodulating activities of different types of
      Japanese rice bran, we analyzed the effects of extracts of red, brown and black
      rice brans on the cell proliferation and cytokine production of mouse
      immunocompetent cells by cell culture experiments. Methanol extracts of these
      rice brans showed suppressive activities against the proliferative response (3H
      thymidine incorporation) of mouse spleen cells induced by concanavalin A (Con A)
      or lipopolysaccharide (LPS) in the cell culture experiments. Although the black
      and brown rice bran extracts showed suppressive effects on the production of
      interferon gamma (IFN gamma) or interleukin 6 (IL-6) in mouse spleen cells
      induced by Con A or LPS, the red rice bran extract exhibited stimulatory effects
      on the same cytokine-producing systems. Furthermore, when the effects of these
      extracts on the production of macropahage-derived inflammatory cytokines such as
      interleukin-1alpha (IL-1alpha) and tumor necrosis factor alpha (TNF-alpha) were
      assayed, the red rice bran extract caused a stimulatory effect on the IL-1alpha
      production from mouse macrophages induced by LPS, but did not show a significant
      effect on TNF-alpha production. However, the brown and black rice bran extracts
      exhibited significant inhibitory effects on the production of IL-1alpha and TNF
      alpha in the same macrophage culture experiment. A possible mechanism of the
      immunomodulating activities of the rice bran extracts and the
      immunopharmacological significance of these findings are discussed.

PMID- 19750931
TI  - Cobalt concentration in urine as an indicator of occupational exposure to low
      level cobalt oxide.
AB  - The aim of this study was to verify the relationship between the cobalt oxide
      concentration in air and the cobalt concentration in urine. In the first study,
      we measured the cobalt concentration in the urine of 16 workers exposed to cobalt
      oxide in a Digital Video Cassette manufacturing plant at the beginning and end of
      their workshift during 2 working cycles. In the second study, we measured the
      exposure level to cobalt oxide and the cobalt concentration in urine at the end
      of the workshift of other 16 workers on 3 out of 5 consecutive work days (Monday,
      Wednesday and Friday). Four workers among the 16 participated twice. In the first
      study, the cobalt concentration in the urine increased about 1.5-3 fold during
      each workshift and then tended to decrease rapidly to the control value before
      the next workshift. In the second study, we examined the relationship between air
      and urine concentration using 22 samples after excluding data from workers with
      dust respirators. Comparing the air and urine concentrations for samples under 30
      microg/m3 (n = 20), a significant correlation was found (r = 0.76). These results
      indicate that most of the inhaled cobalt oxide was excreted rapidly, and a good
      relationship was found between air and urine concentrations at the end of the
      workshift when the exposure level was under 30 microg/m3. Therefore, the cobalt
      concentration in urine at the end of a workshift can be used as an indicator of
      one-day exposure to cobalt oxide when the exposure is low level.

PMID- 19750932
TI  - A walker with a device of partial suspension for patients with gait disturbance:
      body weight supported walker.
AB  - We developed a walker, the Body Weight Supported (BWS) Walker, with a device of
      partial suspension for patients with gait disturbance. It consists of a light
      frame with casters, a harness, and a winch system. One therapist alone can
      perform gait training safely with the BWS Walker without any additional physical
      load, even if a patient has severe gait disturbance, and the therapist can
      concentrate on evaluating and improving the patient' s standing balance and gait
      pattern. Because the BWS Walker is less expensive, simpler, and easier to operate
      than other BWS systems, we believe the BWS Walker can be widely applicable in
      training for patients with severe and moderate gait disturbance.

PMID- 19750933
TI  - [A method to extract signals related to fatigue during visual display terminal
      (VDT) operation using independent component analysis].
AB  - With the recent, rapid developments of computers, adaptation between the human
      being and computer is being improved. On the other hand, mental fatigue is
      increased by continuous, long-time use. The problem of mental fatigue is now a
      new focus of research. This study proposes a method of evaluating mental fatigue.
      In this study, we used a method to extract signals related to fatigue using
      Independent Component Analysis (ICA). The subjects were 10 male students. After
      assuming a workload of simulated visual display terminal (VDT) operation for 30
      min, the subjects sat in a relaxed position for 30 min. In this process, we
      measured work performance, subjective symptoms of feelings of fatigue and
      physiological measures. As a result, there was a high value of the correlation
      coefficient between these signals and the subjective symptoms of feeling of
      fatigue. We suggest that by using ICA we can determine the relationship between
      Independent Components and subjective feelings of fatigue for those under work
      stress, work strain and in a state of fatigue and stress. However, further
      experiments are needed to obtain conclusive findings of our research.

PMID- 19750934
TI  - [Changes of working responsibilities and intentions of industrial physicians who
      are graduates of University of Occupational and Environmental Health, Japan, in
      2001 and 2008 questionnaire analyses].
AB  - To investigate the working responsibilities and intentions of industrial
      physicians who are graduates of University of Occupational and Environmental
      Health, Japan (UOEH), we performed a questionnaire survey in 2008 and compared
      the results with those of 2001. To industrial physicians belonging to a company
      or occupational health organization, we dispatched a questionnaire and asked them
      to return it with an answer. The items to investigate included their careers and
      working activities and their intentions to their responsibilities. We obtained
      the following results. 1. The dissatisfaction with salary and official position
      was mostly reduced to 24.7% from 29.2% and 19.7% from 29.9%. 2. The practical
      duty of medical examination of workers and the subsequent management was
      decreased to 51.5% from 74.7%, while mental health support and the advice on
      severe health issues such as excess work death were increased to 85.6% from 54.5%
      and 32.4% from 22.1%. 3. Concerning the working status of industrial physicians,
      the ratio of the answer of "The industrial physician duties are not positively
      evaluated by his or her company" was decreased to 23.1% from 32.5%. The
      investigation of 2008 revealed that the situation of UOEH graduated industrial
      physicians was substantially improved concerning the dissatisfaction with salary
      and official position, as compared with the study of 7 years before.

PMID- 19750935
TI  - [Stressor among nurses in a psychiatric department--comparison between acute and
      recuperation wards].
AB  - The aim of the present study is to identify stressors (causes of stress) for
      psychiatric department nurses, and to compare the differing stress variables and
      levels of stress encountered in the acute ward and the recuperation ward. The
      study uses a brief work stress questionnaire and then asks 24 questions relating
      to the particular stresses that nurses in a psychiatric department may encounter
      and the length of time they are exposed to them. Answers were obtained from 36
      nurses and associate nurses in two psychiatric departments (breakdown: Hospital A
      psychiatric department acute ward, 11 nurses; Hospital B psychiatric department
      recuperation ward, 25 nurses). Each subscale was analyzed using factor analysis,
      and the factor scores and item score were analyzed using Two-way ANOVA. The
      results of this analysis show that the factor scores for recuperation ward nurses
      were significantly higher than those for nurses from acute ward in the
      "atmosphere" factor from the brief work stress questionnaire, and in all factors
      ("knowledge and technology in nursing", "actual caring", "fear of violence" and
      "directionality of work") in the subscale "Stressors among Nurses in Psychiatric
      Department", indicating that nurses in recuperation ward had high levels of
      stress.

PMID- 19750937
TI  - Volatile C8 compounds and pseudomonads influence primordium formation of Agaricus
      bisporus.
AB  - Primordium formation of Agaricus bisporus depends on the presence of a casing
      layer containing stimulatory bacteria and on sufficient air exchange. The
      influence of specific pseudomonad populations and volatile organic compounds
      (VOC) on primordium formation of A. bisporus was studied in microcosm cultures.
      VOC produced by A. bisporus mycelium were predominantly C8 compounds, some of
      which could inhibit primordium formation, with 1-octen-3-ol being most
      inhibitory. A VOC produced by the rye grain substrate, 2-ethyl-1-hexanol, on
      which A. bisporus was grown also inhibited primordium formation. 2-Ethyl-1
      hexanol and 1-octen-3-ol were metabolized by pseudomonad populations and adsorbed
      by activated charcoal, with both modes of removal enabling primordium formation
      in the casing. Removal of VOC by ventilation also enabled primordium formation to
      occur under axenic conditions. The presence of 2-ethyl-1-hexanol and 1-octen-3-ol
      in the microcosms resulted in higher total bacterial and pseudomonad populations
      in the casing. The stimulatory effects of the casing and its microbiota and air
      exchange on primordium formation of A. bisporus at least partly are due to the
      removal of inhibitory C8 compounds produced by the mycelium and its substrate.
      Monitoring and controlling the levels of these inhibitory VOC in mushroom culture
      should enable primordium formation of A. bisporus to be more efficiently and
      precisely controlled.

PMID- 19750938
TI  - Molecular diversity of myxomycetes associated with decaying wood and forest floor
      leaf litter.
AB  - Denaturing gradient gel electrophoresis (DGGE) fingerprinting was used to assess
      the molecular diversity of myxomycetes from environmental samples (decaying wood
      and forest floor litter) collected at the Mushroom Research Centre in northern
      Thailand. Total genomic DNA was extracted directly from environmental samples on
      which myxomycetes were not apparent. Part of the small subunit ribosomal RNA gene
      (SSU rDNA) was amplified and DNA sequences analyzed. DGGE gels revealed up to 17
      operational taxonomic units (OTU) from decaying wood and 10 OTU from forest floor
      litter samples, but only seven (wood) and six (litter) OTU could be re-amplified
      and/or sequenced. Based on results obtained with the BLAST analysis program, the
      species involved appeared to correspond most closely to Diderma saundersii,
      Didymium iridis, Stemonitis flavogenita and Hyperamoeba sp. strain W2i on
      decaying wood and to Diderma saundersii and Physarum didermoides on forest floor
      litter. Our results suggest that then PCR-DGGE can be used to obtain data on the
      presence of myxomycetes in their primary microhabitats without the need to
      observe the sporocarps of these organisms. As such the technique would seem to
      have considerable potential for contributing to a more complete understanding of
      myxomycete diversity and ecology in terrestrial ecosystems.

PMID- 19750939
TI  - The diversity of arbuscular mycorrhizal fungi amplified from grapevine roots
      (Vitis vinifera L.) in Oregon vineyards is seasonally stable and influenced by
      soil and vine age.
AB  - The diversity of arbuscular mycorrhizal fungi (AMF) in 10 Oregon vineyards was
      assessed by examining spores in soil and amplifying mycorrhizal DNA from roots.
      Seventeen spore morphotypes were found in soil, including seven species in the
      Acaulosporaceae. Eighteen phylotypes were amplified from grape roots with AM1 and
      NS31 primers, and clones were dominated by Glomus spp. (> 99%). A few clones (<
      1%) representing a single phylotype within Gigasporaceae, and a single clone
      within Archaeosporaceae were amplified from roots with AM1-NS31 primers. A
      separate experiment employing known proportions of grape roots colonized by
      Glomus intraradices or by Gigaspora rosea showed that fungi within Gigasporaceae
      might be underrepresented in clone abundance when Glomus spp. co-occur in roots.
      No clones representing fungi within the Acaulosporaceae were amplified from
      vineyards, although specific fungi within Acaulosporaceae were shown to colonize
      Pinot noir roots in sterilized soil and were amplified from these roots. Four
      Glomus phylotypes, including G. intraradices, were found in roots from all 10
      vineyards, and these fungi accounted for 81% of clones. AMF phylotypes amplified
      from roots did not change during the growing season, although six phylotypes
      varied with soil type. The presence of three phylotypes was affected by vineyard
      age, and phylotype richness appeared to decline as vineyard age increased beyond
      20 y. PCA analysis supported the hypothesis that the AMF community is different
      in red-hill soils than in valley soils and indicated certain phylotypes might be
      associated with lower soil and vine nutrient status. However, the changes in the
      AMF community in grape roots across vineyards were subtle because most root
      samples were dominated by the same three or four phylotypes. A separate analysis
      using primers to amplify AMF from the Archeasporaceae/Paraglomeraceae showed most
      root samples also were colonized by at least one Paraglomus or Archaeospora
      phylotype.

PMID- 19750940
TI  - Arbuscular mycorrhizae of dominant plant species in Yungas forests, Argentina.
AB  - In Argentina the Yungas forests are among the ecosystems most affected by human
      activity, with loss of biodiversity. To assess the arbuscular mycorrhizal (AM)
      colonization and the arbuscular mycorrhizal fungi (AMF) spore numbers in these
      ecosystems, the roots of the most dominant native plants (one tree, Alnus
      acuminata; three herbaceous, Duchesnea indica, Oxalis conorrhiza, Trifolium aff.
      repens; and one shrub, Sambucus peruviana) were studied throughout the year from
      two sites of Yungas forests. Assessments of mycorrhizal colonization (percent
      root length, intraradical structures) were made by washing and staining the
      roots. Soil samples of each plant species were pooled and subsamples were
      obtained to determine AM spore numbers. The herbaceous species formed both Arum-
      and Paris-type morphologies, whereas the tree and the shrub species formed
      respectively single structural types of Arum- and Paris-type. AM colonization,
      intraradical fungi structures and AMF spore numbers displayed variation in
      species, seasons and sites. D. indica showed the highest AM colonization, whereas
      the highest spore numbers was observed in the rhizosphere of A. acuminata. No
      correlation was observed between spore numbers and root length percentage
      colonized by AM fungi. Results of this study showed that Alnus acuminata is
      facultatively AM. The AM colonization, intraradical fungi structures and AMF
      spore numbers varied in species depending on phenological, climatic and edaphic
      conditions.

PMID- 19750941
TI  - Morphological measurements and ITS sequences show that the new alder rust in
      Europe is conspecific with Melampsoridium hiratsukanum in eastern Asia.
AB  - Three species of Melampsoridium have been reported to infect hosts in genus
      Alnus. An epidemic of foliar rust affecting A. glutinosa and A. incana began in
      Europe in the mid-1990s, and the associated pathogen was identified as
      Melampsoridium hiratsukanum based on morphology. In this investigation we
      analyzed the morphology and genetic variation of alder rusts from Europe and
      Japan and the host specificity of the European epidemic rust. Our results showed
      that two rusts occur on the leaves of alders native to northern Europe; in
      Scotland an endemic rust indistinguishable from M. betulinum occurs, whereas
      alders in areas of Europe affected by the current epidemic were infected by M.
      hiratsukanum. M. hiratsukanum from naturally infected alder in Finland produced
      aecia on all Larix species tested but did not infect Betula leaves.

PMID- 19750942
TI  - Liquid culture and growth quantification of the seagrass pathogen, Labyrinthula
      spp.
AB  - Symptoms characteristic of wasting disease, thought to result from infection by
      protozoan pathogens (i.e. Labyrinthula spp.), are a common phenomenon affecting
      seagrass species worldwide. However relatively little is known about factors that
      control the survival and success of Labyrinthula in part due to the difficulty
      associated with quantifying the growth of this organism. Here we describe a
      simple and inexpensive method for measuring growth of Labyrinthula in liquid
      culture that takes into consideration both cell density and areal spread. The
      technique allows for examination of the effects of both abiotic and biotic
      factors on the growth of Labyrinthula apart from its seagrass host, separating
      the effects of environmental condition on the host from their effects on the
      pathogen.

PMID- 19750943
TI  - Molecular and phenotypic characterization of three phylogenetic species
      discovered within the Neofisicoccum parvum/N. ribis complex.
AB  - Neofusicoccum parvum and N. ribis are closely related species whose identities
      often have been confused. These fungal plant pathogens were identified recently
      as the most abundant species of Botryosphaeriaceae (Ascomycetes) isolated from
      native Syzygium cordatum trees in South Africa. In another study using multiple
      gene genealogies from five nuclear loci three undescribed cryptic phylogenetic
      species as well as N. parvum were identified among 30 of these isolates. The aim
      of this study was to clarify the identity of the remaining isolates in the N.
      parvum/N. ribis complex from S. cordatum in South Africa, to describe newly
      identified cryptic species and to test their pathogenicity. Based on the RNA
      polymerase II subunit (RPB2) sequence comparisons, the isolates were identified
      as N. parvum or one of three previously recognized phylogenetic species that are
      described here as N. cordaticola, N. kwambonambiense and N. umdonicola. These
      species cannot be separated a priori based on morphological characteristics,
      although a posteriori analysis of variance showed that the differences in
      conidial length and width between the species were statistically significant. The
      isolates of the newly described species as well as N. parvum and N. ribis were
      tested for pathogenicity on S. cordatum under greenhouse conditions. Isolates
      representing the three new species were significantly more aggressive than N.
      parvum and N. ribis with N. kwambonambiense being the most aggressive. This study
      resolved long-standing questions of identity of species within N. parvum/N. ribis
      complex and lays a foundation for further studies on this group of pathogens.

PMID- 19750944
TI  - What is the value of ITS sequence data in Colletotrichum systematics and species
      diagnosis? A case study using the falcate-spored graminicolous Colletotrichum
      group.
AB  - Because the genus Colletotrichum is among the most important groups of plant
      pathogenic fungi worldwide, the ability to accurately diagnose species is vital
      for the implementation of effective disease control and quarantine measures.
      Although the long-standing, unresolved taxonomic issues in the genus have
      recently begun to be addressed through multi-locus phylogenetic research, the
      tools most commonly used for Colletotrichum species identification are either
      insufficiently variable (e.g. morphology), or homoplasic (e.g. morphology and
      host range criteria). In this study, using the systematically well-defined
      falcate-spored, grass-associated group (FG) of Colletotrichum as a model, we test
      the utility of ITS sequence data to diagnose species affiliations through
      similarity-based searches of the NCBI GenBank database or by means of gene trees
      constructed using phylogenetic methods. 43% of all Colletotrichum sequences
      accessioned by GenBank are from the ITS region, making it the single most common
      sequence curated by the community; however, 34% of the ITS accessions existed
      only as sequence data in the database, with no associated publication. Using
      Colletotrichum ITS sequence data from 53 FG defined isolates and 16 falcate
      spored, non-graminicolous isolates to perform GenBank BLASTN searches, we found
      that erroneous identifications occurred for 86% of the 14 species tested. In
      contrast, the phylogenetic tree generated by the ITS sequence data, although
      poorly supported by bootstrap values, correctly grouped most of the species, but
      10% of the individual isolates were incorrectly placed. From this study, we
      conclude that the currently available infrastructure of Colletotrichum ITS
      sequence data may yield unreliable species diagnoses, particularly if sequence
      similarity alone is the only criterion applied.

PMID- 19750945
TI  - Perenniporiella chaquenia sp. nov. and further notes on Perenniporiella and its
      relationships with Perenniporia (poriales, basidiomycota).
AB  - Perenniporiella chaquenia sp. nov. is described from Argentina. New records of P.
      pendula and P. micropora are discussed. A key to Perenniporiella species is
      presented. Preliminary phylogenetic relationships of Perenniporiella are inferred
      from parsimony and Bayesian analysis of a combined set of DNA sequence data
      (nuclear ribosomal partial LSU and ITS). It demonstrated that Perenniporiella
      forms a well resolved monophyletic clade distantly related to Perenniporia s.s.
      It also clearly showed that within Perenniporia as usually conceived other
      morphologically homogeneous group of taxa, such as the P. ochroleuca or P. vicina
      alliances, form well resolved clades, which could be recognized as distinct
      genera. The differentiation of the hyphal system and the basidiospores morphology
      are outlined as critical features for the definition of genera in the
      Perenniporia complex.

PMID- 19750946
TI  - New species of Rhachomyces from Ecuador, one of which is dimorphic.
AB  - Six new species of Rhachomyces from Ecuador are described and illustrated. These
      are R. dimorphus, parasitic on Diploharpus rossii (Carabidae, Perigoninae); R.
      elsae, parasitic on Adelopsis carolinae (Cholevidae, Ptomaphaginae); R. falcatus,
      parasitic on Palaminus sp. (Staphylinidae, Paederinae); R. moreti, parasitic on
      Trechisibus calathiformis (Carabidae, Trechinae); R. otongaensis, parasitic on
      Perigona sp. (Carabidae, Perigoninae); and R. venustus, parasitic on Megalopinus
      robustus (Staphylinidae, Megalopsidiinae). Rhachomyces dimorphus is peculiar,
      displaying two different growth forms, one of which is found on the left foreleg
      of male host insects, the other on the inferior, posterior margin of the
      prothorax of females. Each of the other new species also displays one or more
      unusual features.

PMID- 19750947
TI  - A new Neotyphodium species from Festuca parvigluma Steud. grown in China.
AB  - Neotyphodium species evolved from Epichloe species and are asexual, seedborne
      endophytes in many cool-season grasses. Here we propose a new species inhabiting
      Festuca parvigluma native to China. Morphology, host specificity and molecular
      phylogenetic evidence supported recognition of this new species. Sequences of
      beta-tubulin gene (tubB) introns and translation elongation factor 1-alpha gene
      (tefA) introns were present as two copies in all five isolates examined. In
      phylogenetic analyses copy 1 was closely related to E. yangzii in the EBY clade
      and copy 2 with E. typhina in the ETC clade, indicating this new species might
      have originated as a result of hybridization between members of these two clades.
      Referring to the distribution area of host plants, Neotyphodium sinofestucae is
      proposed for this new species.

PMID- 19750948
TI  - Molecular diversity and host specificity of termite-associated Xylaria.
AB  - Studies have revealed that some Xylaria species were closely associated with
      fungus-growing termite nests. However this relationship rarely had been
      investigated and the host specificity of termite-associated Xylaria was not yet
      clearly established. Eighteen Xylaria rDNA-ITS sequences were obtained from
      fungus combs belonging to 11 Macrotermitinae species from eight regions. Low
      diversity was found between isolates, and nine sequences were retrieved. Termite
      associated Xylaria were shown to be monophyletic, with three main clades, all
      including strains from various termite hosts and geographical localities. This
      new molecular study shows no species specificity with respect to fungus-growing
      termites, which suggests that there might be substrate specialization.

PMID- 19750949
TI  - Tetracladium nainitalense sp. nov., a root endophyte from Kumaun Himalaya, India.
AB  - An aquatic hyphomycete, Tetracladium nainitalense sp. nov., isolated as a root
      endophyte from riparian plants from Nainital, Kumaun Himalaya, India, is
      illustrated and described. The new species is characterized by laterally
      applanate conidia appearing lobate, with typically four rounded apices and
      lacking filiform, acicular or subulate elements. An updated key to the species of
      Tetracladium is provided.

PMID- 19750950
TI  - Rhizidium phycophilum, a new species in Chytridiales.
AB  - Molecular and ultrastructural investigations are revealing unrealized diversity
      among chytrids as the taxonomic revision of order Chytridiales (Chytridiomycota)
      progresses. During a biodiversity survey of soil-inhabiting chytrids in Australia
      an undescribed chytrid was isolated from a soil sample collected in a cool
      temperate rainforest of New South Wales, Australia. Combined zoospore
      ultrastructure analysis and molecular phylogenetic analyses of partial LSU rRNA
      and ITS1-5.8S-ITS2 sequences demonstrated this chytrid was a new species within
      Chytridiales and possessed distinctive zoospore architecture previously unknown.
      Herein we delineate a new Rhizidium species in Chytridiales based on molecular
      monophyly and unique subcellular organization of the zoospore.

PMID- 19750951
TI  - Description and life cycle of a new Didymium (Myxomycetes) from arid areas of
      Argentina and Chile.
AB  - A new species of Didymium (Myxomycetes), D. infundibuliforme, is described
      herein, and details are provided on its life cycle as observed in spore to spore
      culture on agar. The new species was recorded during intensive studies of areas
      of the Monte Desert in Argentina and the Atacama Desert in Chile. It has been
      collected directly in the field in both countries on several occasions over 4 y
      and isolated in moist chamber cultures prepared with material from native plant
      species. The characters that make this species unique in the genus are its funnel
      shape sporocarps with white stalks, the apical circumscissile dehiscence of the
      sporotheca that causes the base to resemble a calyculus and the ornamentation on
      the spores. The morphology of specimens of this new myxomycete was examined with
      scanning electron microscopy and light microscopy, and micrographs of relevant
      details are included in this paper.

PMID- 19750952
TI  - Systematic analysis of the falcate-spored graminicolous Colletotrichum and a
      description of six new species from warm-season grasses.
AB  - Species limits in the fungal genus Colletotrichum are traditionally distinguished
      by appressorial and/or conidial morphology or through host plant association, but
      both criteria are criticized for their inability to resolve distinct taxa. In
      previous research eight novel falcate-spored Colletotrichum species were
      identified from graminicolous hosts using multilocus molecular phylogenetic
      analysis. In the present work formal descriptions and illustrations are provided
      for six of the new taxa: C. hanaui sp. nov., C. nicholsonii sp. nov., C. paspali
      sp. nov., C. jacksonii sp. nov., C. miscanthi sp. nov. and C. axonopodi sp. nov.;
      and an emended description with epitypification is provided for C. eleusines.
      Comparison of hyphopodial appressoria and host association against phylogenetic
      species boundaries and evolutionary relationships in the graminicolous
      Colletotrichum group demonstrate that, while these characters can be useful in
      combination for the purpose of species diagnosis, erroneous identification is
      possible and species boundaries might be underestimated if these characters are
      used independently, as exemplified by the polyphyletic taxa C. falcatum.
      Appressoria have been subject to convergent evolution and were not predictive of
      phylogenetic relationships. Despite these limitations, the results of this work
      establish that in combination appressorial and host range characters could be
      used to generate informative dichotomous identification keys for Colletotrichum
      species groups when an underlying framework of evolutionary relationships,
      taxonomic criteria and nomenclature have been satisfactorily derived from
      molecular systematic treatments.

PMID- 19750953
TI  - Taxonomic and nomenclatural aspects of Hypoxylon taxa from southern South America
      proposed by Spegazzini.
AB  - The holotypes and isotypes of 20 Hypoxylon taxa described by Spegazzini have been
      examined and their taxonomic positions and nomenclatural problems are discussed.
      Two new combinations, Annulohypoxylon apiahynum comb. nov. and A. subeffusum
      comb. nov., are proposed. H. goliath is considered a synonym of Rosellinia
      bunodes. H. albostigmatosum and H. guarapiense are synonyms of H. anthochroum, H.
      anthracoderma of H. monticulosum, H. mbaiense of H. notatum, H. paulistanum of H.
      diatrypeoides, H. plumbeum and H. rubiginosum var. microcarpum of H. perforatum.
      H. porteri and H. intermedium belong in Biscogniauxia capnodes, H. puiggarii in
      Annulophypoxylon subeffusum, H. subvinosum. in H. lenormandii, H. turbinatum var.
      guaraniticum in Phylacia turbinata and H. valsarioides in Creosphaeria sassafras.
      H. leptascum is transferred to A. leptascum, H. circostomum to Nemania circostoma
      and H. latissimum to N. latissima. The holotype of H. albostigmatosum has been
      recovered, thus the lectotypification by Shear no longer is needed. H.
      subnigricans and H. umbilicatum are confirmed as good taxa. H. anthochroum and H.
      lenormandii are reported as first records from Argentina (Tucuman).

PMID- 19750954
TI  - George Baker Cummins 1904-2007.

PMID- 19750955
TI  - Definition of health promotion 2.0: embracing passion, enhancing motivation,
      recognizing dynamic balance, and creating opportunities.

PMID- 19750956
TI  - Do alcohol consumers exercise more? Findings from a national survey.
AB  - PURPOSE: Investigate the relationship between alcohol consumption and physical
      activity because understanding whether there are common determinants of health
      behaviors is critical in designing programs to change risky activities. DESIGN:
      Cross-sectional analysis. SETTING: United States. SUBJECTS: A sample of adults
      representative of the U.S. population (N = 230,856) from the 2005 Behavioral Risk
      Factor Surveillance System. MEASURES: Several measures of drinking and exercise
      were analyzed. Specifications included numerous health, health behavior,
      socioeconomic, and demographic control variables. RESULTS: For women, current
      drinkers exercise 7.2 more minutes per week than abstainers. Ten extra drinks per
      month are associated with 2.2 extra minutes per week of physical activity. When
      compared with current abstainers, light, moderate, and heavy drinkers exercise
      5.7, 10.1, and 19.9 more minutes per week. Drinking is associated with a 10.1
      percentage point increase in the probability of exercising vigorously. Ten extra
      drinks per month are associated with a 2.0 percentage point increase in the
      probability of engaging in vigorous physical activity. Light, moderate, and heavy
      drinking are associated with 9.0, 14.3, and 13.7 percentage point increases in
      the probability of exercising vigorously. The estimation results for men are
      similar to those for women. CONCLUSIONS: Our results strongly suggest that
      alcohol consumption and physical activity are positively correlated. The
      association persists at heavy drinking levels.

PMID- 19750957
TI  - U.S. consumer demand for restaurant calorie information: targeting demographic
      and behavioral segments in labeling initiatives.
AB  - PURPOSE: To identify different segments of U.S. consumers based on food choices,
      exercise patterns, and desire for restaurant calorie labeling. DESIGN: Using a
      stratified (by region) random sample of the U.S. population, trained interviewers
      collected data for this cross-sectional study through telephone surveys. SETTING:
      Center for Rural Studies U.S. national health survey. SUBJECTS: The final sample
      included 580 responses (22% response rate); data were weighted to be
      representative of age and gender characteristics of the U.S. population.
      MEASURES: Self-reported behaviors related to food choices, exercise patterns,
      desire for calorie information in restaurants, and sample demographics. ANALYSIS:
      Clusters were identified using Schwartz Bayesian criteria. Impacts of demographic
      characteristics on cluster membership were analyzed using bivariate tests of
      association and multinomial logit regression. RESULTS: Cluster analysis revealed
      three clusters based on respondents' food choices, activity levels, and desire
      for restaurant labeling. Two clusters, comprising three quarters of the sample,
      desired calorie labeling in restaurants. The remaining cluster opposed restaurant
      labeling. Demographic variables significantly predicting cluster membership
      included region of residence (p < .10), income (p < .05), gender (p < .01), and
      age (p < .10). CONCLUSIONS: Though limited by a low response and potential self
      reporting bias in the phone survey, this study suggests that several groups are
      likely to benefit from restaurant calorie labeling. Specific demographic clusters
      could be targeted through labeling initiatives.

PMID- 19750958
TI  - Effects of a multilevel dietary intervention in religious organizations.
AB  - PURPOSE: This study examined how to improve dietary habits of individuals from
      the general public. DESIGN: The Eating for a Healthy Life project was a
      randomized trial. SETTING: The study was conducted among members of religious
      organizations (ROs). SUBJECTS: Participants were a sample of RO members.
      INTERVENTION: The intervention was a multilevel package, based on our previous
      experience, designed to lower fat and increase fruit and vegetable consumption.
      MEASURES: The Eating Behaviors Questionnaire was administered preintervention and
      postintervention, together with 24-hour food recalls in a randomly selected
      subset. Analysis. Linear mixed models were used to evaluate the study's
      intervention, incorporating the design effects of blocking, intraclass
      correlation within RO, and correlation between the preintervention and
      postintervention points. RESULTS: Participants (n = 2175) reported significantly
      healthier dietary behaviors in intervention ROs at the 12-month follow-up period,
      compared to participants in the comparison ROs, for a fat scale change of .08
      summary scale points and an adjusted intervention effect of .06 overall.
      CONCLUSION: Dietary intervention through ROs is a positive and successful method
      of changing dietary habits.

PMID- 19750959
TI  - Comparing individualized rehabilitation to a group wellness intervention for
      persons with multiple sclerosis.
AB  - PURPOSE: Compare the efficacy of two interventions designed to promote health and
      physical activity (PA). DESIGN: This study was a randomized clinical trial using
      a time series design. Subjects were randomized into individualized physical
      rehabilitation (IPR) and group wellness intervention (GWI). Primary
      questionnaires were administered twice preintervention and twice
      postintervention. Physical fitness and PA frequency were assessed preintervention
      and postintervention. SETTING: Clinic based in a metropolitan area. SUBJECTS:
      Fifty volunteers with multiple sclerosis. INTERVENTIONS: IPR consisted of four
      physical therapy sessions plus three telephone calls. GWI consisted of seven
      educational sessions. MEASURES: Primary: SF-36 Health Survey, Modified Fatigue
      Impact Scale, Mental Health Inventory. Secondary: physical assessment, PA
      frequency. ANALYSIS: Stability of primary questionnaires between the two pretests
      was examined. Efficacy of interventions was evaluated by multivariate analysis of
      variance (MANOVA) and effect sizes. RESULTS: Primary measures were stable between
      pretests. MANOVA showed nonsignificant differences between interventions. Eight
      weeks postintervention, both groups had improved PA, fatigue, resting heart rate,
      and strength. Effect sizes suggested that IPR had a greater effect on preventing
      decline of physical health, whereas GWI had a greater effect on improving mental
      health. CONCLUSION: Preliminary evidence indicated that health and PA improved in
      both groups. Effect sizes suggested that participants benefited more physically
      from IPR and more mentally from GWI. Future research should determine whether
      combining therapeutic exercise with group education improves both mental and
      physical health.

PMID- 19750960
TI  - Associations of cycling with urban sprawl and the gasoline price.
AB  - PURPOSE: Determine the relationships between cycling and urban sprawl and between
      cycling and the gasoline price. ANALYSIS: Cross-sectional multivariate regression
      analyses using pooled data from two individual-level national surveys to analyze
      the effects of variations in levels of urban sprawl and the gasoline price on
      cycling as a form of physical activity. SETTING: Metropolitan areas
      representative of the U.S. population, 1990 to 2001. SUBJECTS: Behavioral Risk
      Factor Surveillance System: 146,730 individuals at least 18-years-old in the
      United States; Nationwide Personal Transportation Survey: 73,903 individuals at
      least 18-years-old in the United States. MEASURES: Self-reported information on
      bicycling served as the dependent variable. Urban sprawl and the gasoline price
      served as key independent variables. RESULTS: Living in a metropolitan area with
      a lower degree of urban sprawl increased the probability of cycling in the past
      month by 3.4 to 4.4 percentage points and 1.6 to 2.1 percentage points from the
      means for men and women, respectively. Increasing the gasoline price by one
      dollar increased the probability of cycling by 4.3 to 4.7 percentage points and
      2.9 to 3.5 percentage points for men and women, respectively. CONCLUSION: Results
      indicate that the prevalence of cycling is higher in less sprawling areas and
      areas with higher gasoline prices. More research is needed to refine results on
      how individuals respond to incentives and the roles that monetary and time costs
      play in improving public health.

PMID- 19750961
TI  - Factors associated with incidental sickness absence among employees in one health
      care system.
AB  - PURPOSE: Assess the association of taking incidental sickness absence with health
      risks and health status. DESIGN: Observational. SETTING: One Midwest health care
      system. SUBJECTS: Individuals who were employed for 2 years (2006-2007) and had
      completed at least one health risk appraisal (HRA) in 2007 (N = 3790). MEASURES:
      Outcomes were any incidental sickness absence and absence duration in 2007
      measured by an absence tracking system. Health risks and health status were
      estimated by HRAs. Program participation was captured using 7-year HRA data and 5
      year wellness data. ANALYSIS: Multivariate, binary logistic regression for the
      probability of taking any absence day among the overall population as well as
      four demographic subgroups; proportional odds model for the probability of taking
      more absence days. RESULTS: Different patterns were observed in association with
      taking incidental sickness absence among age and gender subgroups. Among the
      overall population, three health risks (smoking overweight, and use of medication
      for relaxation) were positively associated with taking absence (at least p < .05
      for all three health risks). Participation in a wellness program for more years
      was also associated with a less likelihood of taking absence (odds ratio, .72; p
      = .002). Results from the proportional odds model were consistent with results
      from the binary logistic regression. CONCLUSION: Sickness absence is an important
      productivity concern of employers. Employers may implement early interventions to
      focus on preventable causes. Special interventions may target absence-causing
      risks such as smoking behavior and excess body weight. Study limitation includes
      a lack of measures for psychosocial work environment.

PMID- 19750962
TI  - Potential societal savings from reduced sodium consumption in the U.S. adult
      population.
AB  - PURPOSE: Policies that address the food environment at the population level may
      help prevent chronic disease, but their value to society is still uncertain.
      Dietary sodium is linked to increased prevalence of hypertension, a primary risk
      factor for cardiovascular and renal diseases. This study calculates the potential
      societal savings of reducing hypertension and related cardiovascular disease via
      a reduction in population-level sodium intake. On average, U.S. adults consume
      almost twice the recommended maximum of dietary sodium, most of it from processed
      foods. DESIGN: This study modeled sodium-reduction scenarios by using a cross
      sectional simulation approach. The model used population-level data on blood
      pressure, antihypertensive medication use, and sodium intake from the National
      Health and Nutrition Examination Survey (1999-2004). This data was then combined
      with parameters from the literature on sodium effects, disease outcomes, costs,
      and quality of life to yield model outcomes. MEASURES: This study calculated the
      following outcome measures: hypertension prevalence, direct health care costs,
      and quality-adjusted life years for noninstitutionalized U.S. adults. ANALYSIS:
      The simulation was conducted with STATA 9.2 and Microsoft Excel. Survey weights
      were used to calculate population averages. RESULTS: Reducing average population
      sodium intake to 2300 mg per day, the recommended maximum for adults, may reduce
      cases of hypertension by 11 million, save $18 billion health care dollars, and
      gain 312,000 QALYs that are worth $32 billion annually. Greater reductions in
      population sodium consumption bring even greater savings to society. CONCLUSIONS:
      Large benefits to society may result from efforts to lower sodium consumption on
      a population level by modest amounts over time. Although savings in direct health
      care costs are likely to be quite high, they could easily be matched or exceeded
      by the value of quality-of-life improvements.

PMID- 19750963
TI  - Best practices for smoking cessation: implications for employer-based programs.
AB  - Tobacco use and smoking continue to be one of the most important potentially
      preventable health problems of the 21st century. A large number of studies
      published in the peer-reviewed literature now inform much of our employer-based
      programming efforts. Worksite settings and health plan member populations are
      served primarily through worksite-based interventions, which are examined in this
      literature review. As a consequence, a number of important resulting "best
      practices" for smoking cessation efforts with employed populations are presented
      for consideration in this edition of The Art of Health Promotion.

PMID- 19750964
TI  - ["Successful career"? What constitutes success in nursing?].

PMID- 19750965
TI  - [The limits of expansion in the inpatient geriatric nursing area: estimates for
      the nursing market].

PMID- 19750966
TI  - [Application of the Verena Tschudin decision model: ethical--moral decisions].

PMID- 19750967
TI  - [Problems in further professional development in geriatric nursing: "success
      through career?"].

PMID- 19750968
TI  - [Academic emphasis in health and nursing care: a necessary development].

PMID- 19750969
TI  - [Interdisciplinary counseling of women with intestinal cancer: counseling brings
      courage].

PMID- 19750970
TI  - [Aspects of introduction of kinesthetics in organizations: "maintaining
      movement"].

PMID- 19750971
TI  - [Added qualifications for the future: study nurse: research, what really helps].

PMID- 19750972
TI  - [Frequent problems of skin protection at work: personal hand care]].

PMID- 19750973
TI  - [A German nationwide unique nursing and social coach education: coaching provides
      knowledge for individual support].

PMID- 19750974
TI  - [Planning a procedure in nursing care--1: Preparing for endotracheal intubation].

PMID- 19750975
TI  - [The oral exam in nursing education--3: Topics 8 and 12: managing complex nursing
      tasks].

PMID- 19750976
TI  - [Collaboration between science and practice: experiences of conducting a nursing
      intervention study].
AB  - In a five-year intervention study about the impact of pre-operative mobilisation
      training session of patients receiving an elective medial laparotomy experiences
      about the collaboration between practice (University Hospital Ulm) and science
      (Hessian Institute of Nursing Research) were made. During the project
      possibilities and borders of clinical nursing research became clear. A research
      question based on practice experiences of nurses helps to develop and maintain
      motivation to conduct a study at a nursing unit. There was a lack of nursing
      knowledge to develop the best possible design, e.g. outcome criteria for
      mobilisation and standardized assessment instruments. The cooperation with other
      health care professionals (human movement science, statistics) was important and
      without difficulties. In Germany, without doctors' agreement and common
      application it is impossible to conduct nursing intervention studies in
      hospitals. It is necessary to train nursing specialists with both scientific and
      clinical competence to explore systematically clinical research questions.

PMID- 19750977
TI  - [Treatment error in administering an enema: a fully manageable risk].

PMID- 19750978
TI  - [From case to case: preventing spinal injuries].

PMID- 19750979
TI  - Cytokines and liver regeneration after partial portal vein ligation in porcine
      experimental model.
AB  - THE AIM OF STUDY: The limits of liver surgery are restricted today by the
      functional reserves of remnant parenchyma. The aim of this article was to
      acquaint the general surgical and medical public with the results of experimental
      liver regeneration stimulated by cytokines and thus to enhance their effort to
      carry on with implementing the research results in clinical practice. METHODS:
      Authors present their experimental model of liver regeneration after ligation of
      portal branches for caudate and right lateral, and right medial liver lobes. The
      regeneration was induced by application of TNF-alpha and IL-6 into the non
      occluded portal branches, and compared with the results of other experimental
      teams. RESULTS AND CONCLUSION: The absolute volume of hypertrophic lobes
      increases after application of TNF-alpha more rapidly, whereas in the control
      group, practically no changes were recorded in hypertrophic liver lobes volumes
      in first three days. The achieved acceleration of growth of hypertrophic liver
      lobes after application of TNF-alpha and IL-6 confirmed the key role of studied
      pleiotropic cytokines in the priming of liver parenchyma regeneration after
      portal vein ligation (Fig. 3, Ref. 26).

PMID- 19750980
TI  - A beneficial influence of provinol on the reduction of allergen induced
      hyperreactivity in guinea pigs.
AB  - BACKGROUND: The anti-inflammatory, anti-allergic, antioxidant properties of
      flavonoids are known in the respiratory tract. We are interested in the role of
      Provinol during an allergic inflammation of the airway. OBJECTIVES: The aim of
      this study was to examine the influence of an acute administration of Provinol on
      tracheal smooth muscle reactivity in guinea pigs and to assess the involvement of
      nitric oxide in the mechanism of Provinol action. METHODS: This experiment was
      performed 14 days after the sensitization of animals by ovalbumin. In vivo, the
      specific airway conductance, as a tracheal smooth muscle reactivity parameter in
      response to bronchoconstrictor histamine, was evaluated after peroral
      administration of Provinol alone or together with L-NAME (N(omega)-nitro-L
      arginine methyl ester). In vitro, Provinol alone or in combination with L-NAME
      were added into an organ baths before the supplement of direct bronchoconstrictor
      histamine, acetylcholine and the allergen ovalbumin in rising concentrations. The
      amplitude of the tracheal smooth muscle contraction, as a tracheal smooth muscle
      reactivity parameter in response to histamine, acetylcholine and ovalbumin was
      evaluated. RESULTS: Our results showed that a Provinol has significant
      bronchodilatory activities both in vivo and in vitro. CONCLUSION: Provinol
      alleviated the contraction of tracheal smooth muscle in guinea pigs sumin. Nitric
      oxide plays an important role in the mechanism of Provinol action (Fig. 2, Ref.
      28n.(Fig. 2, Ref. 28).

PMID- 19750981
TI  - A response to infection in patients with severe sepsis--do we need a "stage
      directed therapy concept"?
AB  - Excessive forms of the response of organism to infection play an important role
      in the pathogenesis of severe sepsis. They may consist of either local pro
      inflammatory response with a massive release of cytokines into the systemic
      circulation, or may be presented as an excessive systemic anti-inflammatory
      response. In the first case, the result is a systemic pro-inflammatory state,
      characterised by natural stages of the inflammatory response, in which
      dysfunction of macrocirculation is followed by microcirculation derangement and
      mitochondrial alteration at the end. These mechanisms are responsible for the
      development of remote organs failure. The result in the second case is a
      deactivation of local immunocompetent cells, which results in the risk of
      uncontrollable growth of microorganisms, especially in organs with an impaired
      antimicrobial barrier. This may explain the clinically observed recurrence of
      septic episodes, when a resolution of infection at one site is later replaced
      with an outbreak of sepsis from another site. A number of therapeutic
      interventions aimed on the management of causes and consequences of systemic pro
      inflammatory state was clinically tested (e.g. antibiotics, goal directed
      hemodynamic support and inhibitors of coagulation) with surprisingly different
      effectiveness. The cause of this difference may lie, apart from the frequently
      discussed inhomogeneity of the studied patient population, also in an incorrect
      timing of the therapeutic interventions, which does not respect natural stages of
      the inflammatory response (Fig. 1, Ref. 40).

PMID- 19750982
TI  - Different head morphology of full-term gypsy and non-gypsy newborns from Slovak
      Republic.
AB  - BACKGROUND: Early detection of cranial growth defects in childhood is extremely
      important for subsequent growth, development of head and could be a screening aid
      for early detection of growth deviations. METHODS: Seven head dimensions and two
      indexes of 90 Gypsy and 99 non-Gypsy newborns from Slovakia were examined to
      asses the potential differences between the groups. RESULTS: Gypsy newborns had
      significantly lower head circumference, lower head length, lower width of head
      basis and facial width compared to non-Gypsy newborns. Gypsy newborns have shown
      significantly higher value of the index cephalicus while in non-Gypsy newborns
      mesocephalic values have been detected. Moreover, Gypsy newborns had
      significantly higher cranium as compared to non-Gypsy. CONCLUSIONS: Gypsy
      subpopulation has a different head morphology compared to the majority of the
      population. Knowledge about the different head morphology between these ethnic
      groups could give us clues about the genetic influences determining head
      morphology in the prenatal development and therefore might be a helpful
      diagnostic tool in neonatology (Tab. 1, Ref. 14).

PMID- 19750983
TI  - Psychoactive substance-related deaths in road traffic accidents in Slovakia
      between 2000 and 2007.
AB  - THE AIM OF THE STUDY: Our study was aimed at fatal road traffic accidents caused
      under the influence of psychoactive substances different from alcohol. METHODS:
      Retrospective analyses of fatalities in 2000-2005 road traffic accidents under
      the influence of psychoactive substances different from alcohol on the behalf of
      National Monitoring Centre for Drugs were carried out in all of 10 Slovak medical
      forensic workplaces supervised by Healthcare Surveillance Authority. The detected
      set of cases was extended by cases reported in 2006 and 2007. RESULTS: A total of
      75 fatalities in road traffic accidents were reported to be incurred under the
      influence of psychoactive substances. Of the latter amount, 42 cases occurred in
      the period 2000-2005 and 33 cases in 2006 and 2007. The set involved 32 drivers,
      12 pedestrians, 4 motorcyclists, 2 cyclists and 25 passengers. The most
      frequently detected substances in the period 2000-2005 were cannabis and
      benzodiazepines. In 2006 and 2007 the increase in substances classified as
      central nervous system stimulants was detected. CONCLUSION: The listed number of
      reported deaths incurred in the whole territory of Slovakia during the 8-year
      period is relatively low in comparison with the total number of fatal road
      traffic accidents. The proved reality represents only the tip of the iceberg and
      suggests that the monitoring of prevalence of psychoactive substances in
      population had some drawbacks (Tab. 4, Ref. 8).

PMID- 19750984
TI  - Cosmetic perfumes vs. human pheromones (natural chemical scents) of the human
      female and male in signalling and performing context of their sexual behaviour.
AB  - Scent communication in man is undoubtedly of importance, although it is
      unconscious, rather than active, as compared to subhuman primates. Besides human
      sexual life it also affects a number of further characteristics of human life and
      its infrastructure including the mother-child relationship, creation of the odour
      basis of the family with the possibility to identify the family members solely by
      their odour as well as other parameters investigated thus far. Pheromones have
      effect upon the selection of a suitable partner of the opposite sex (or of the
      same sex in homosexual partners). The formation of specifically significant
      responses during communication between the two sexes, first of all in sexual life
      and its manifestations, may also be influenced by pheromone-based perfumes or
      classical cosmetic perfumes, as far as they are selected and used appropriately.
      The situation is much easier if the partners are of the olfactory type where for
      both partners the mutual olfactory parameters are the most attractive for their
      sexual life and its parameters, which significantly contributes to the quality of
      their overall coexistence (Ref. 29).

PMID- 19750985
TI  - The genotoxicity and cytotoxicity among patients diagnosed with organophosphate
      poisoning.
AB  - The genotoxicity and cytotoxicity were investigated in 40 patients (20 females
      aged 21.57 +/- 1.42 and 20 males aged 29.35 +/- 3.59) diagnosed at the Emergency
      Department with organophosphate poisoning. Chromosome aberrations (CAs), sister
      chromatid exchanges (SCEs), micronucleus (MN), mitotic index (MI), replication
      index (RI) and nuclear division index (NDI) were evaluated in peripheral bloods
      of patients. The blood samples were collected from the patients on admission to
      the emergency department before treatment and after treatment before being
      discharged from the intensive care unit. The CA, MI and NDI values were increased
      before the discharge when compared to the levels measured on admission. However,
      there are no differences in mean SCE, frequency of MN and RI (Tab. 2, Ref. 42).

PMID- 19750986
TI  - HLA-b27 subtypes in patients with spondylarthropathies, IgE levels against some
      allergens and their relationship to the disease parameters.
AB  - In suitable genetic backgrounds, some exogenous and/or endogenous antigens may
      cause SpA. In this study, we investigated HLA B27 subtypes and its relationship
      to some allergens and clinical findings in a group of SpA patients. Forty-eight
      patients (19F, 29M) with SpA (27 with ankylosing spondylitis, 5 with reactive
      arthritis, 15 undifferentiated and 1 with psoriatic arthritis) were included to
      the study. HLA-B alleles have been assessed using the LiPA (Line Probe Assay)
      reverse hybridization principle method. The allergens studied were following: egg
      white, yolk, wheat flour, hot pepper, tomatoes, olive, onion, chicken, black tea,
      sheep cheese, penicillin panel (m1, m25, m28, m30), fungus panel (m1, m2, m3,
      m6), and housemix panel (e1, e2, d1, d2, m2, m3). 59.3% of the patients were
      positive for HLA-B27. Of these patients, 53.6% had B*2702 allele which was the
      most common, followed by B*2708 (21.1%) and B*2701 (10.5%). HLA-B27 was positive
      in 70% of the ankylosing spondylitis patients and 52% had B*2702 subgroup and B35
      was the most common subgroup among the patients who were HLA-B27 negative.
      Allergic reactions against these 13 allergens were more severe in patients HLA
      B27 positive. The most frequent allergic reactions were against the onion and
      housemix panel, followed by red pepper, tomatoes, sheep cheese and olive. HLA
      B*2702 and HLA-B*2701 subgroups had more severe allergic reactions that
      correlated with a disease severity (p < 0.001). These results indicate that
      B*2702 and B*2708 is more frequent in our region in contrast to B*2705 which is
      more commonly found all around the world and that our region represents a
      heterogeneous distribution. IgE levels against some allergen were found higher in
      patients with SpA (Fig. 2, Tab. 5, Ref. 37).

PMID- 19750987
TI  - Evaluation of upper airway in obstructive sleep apnea-hypopnea syndrome and
      habitual snorers.
AB  - OBJECTIVES: The purpose of this study was to evaluate upper airway in obstructive
      sleep apnea-hypopnea syndrome patients and habitual snorers, and to determine the
      correlation with apnea-hypopnea index. METHODS: 193 patients who applied to our
      Ear Nose Throat Clinic between years 2000 and 2002 with the complaint of
      witnessed snoring and/or apnea were included in the study. Each patient was
      evaluated by a complete head and neck examination and polysomnography. Physical
      examination included anterior rhinoscopy, nasal endoscopy, examination of
      oropharynx and hypopharynx and Muller maneuver. The correlation between the Ear
      Nose Throat examination parameters and the apnea/hypopnea index was investigated.
      RESULTS: Patients were distributed into two groups according to the apnea
      hypopnea index: habitual snorers (34.3%) and obstructive sleep apnea-hypopnea
      (65.7%). There was a statistically significant correlation between apnea-hypopnea
      index and Muller maneuver, tongue base, lateral pharyngeal fold. There was a
      statistically significant correlation between body mass index, Muller maneuver
      and uvula. CONCLUSIONS: Obstructive sleep apnea-hypopnea patients results from
      changes in the upper airway. Anatomic and functional findings correlated with the
      apnea-hypopnea index. In the majority of patients with OSAHS, pharyngeal
      abnormalities and nasal obstruction were found to be statistically significant
      (Tab. 2, Fig. 1, Ref. 14).

PMID- 19750988
TI  - Meningeal carcinomatosis as the first manifestation of malignant carcinomatosis.
AB  - Meningeal carcinomatosis (MC) is a malignant infiltration of the leptomeninges
      and subarachnoid space and can be a devastating complication of a systemic
      malignancy. Although often found in patients with known metastatic malignancies,
      MC can also be the initial manifestation of an underlying malignancy. We report
      four case studies where back pain, dizziness, cognitive decline, headache and
      headache with the cranial nerve VI palsy were the first signs of MC. In two
      cases, adenocarcinoma ventriculi was found, in other one, the markers of the
      gastrointestinal tract malignancy were highly positive but malignity was not
      found, and in the last one, there was a known breast carcinoma. The diagnosis of
      MC requires the finding of malignant cells in the cerebrospinal fluid, but
      sometimes several lumbar punctures are required to establish the diagnosis, and
      also MRI with gadolinium. Finally, we would like to highlight the fact that
      markedly decreased glycorrhachia in cerebrospinal fluid (CSF) can also be the
      first sign of MC (Fig. 6, Tab. 2, Ref. 23).

PMID- 19750989
TI  - Sibutramine--its impact on health-related quality of life and depression among
      adult obese non-diabetic patients.
AB  - BACKGROUND: Obesity is a multifactorial, chronic disorder that has reached
      epidemic proportions in most industrialised countries and is threatening to
      become a global epidemic. AIMS: The pilot study evaluates the effect of
      sibutramine therapy on health-related quality of life and occurence of depression
      symptoms among adult obese non-diabetic patients. PATIENTS AND METHODS: This
      study was prospective and longitudinal. It was conducted at the Department of
      Hygiene of Faculty of Military Health Sciences in Hradec Kralove, Czech Republic.
      Dates were obtained during year 2007. Twenty two adult obese non-diabetic
      patients (6 males and 16 females) were treated with sibutramine in dose of 10 mg
      daily. All of these 22 patients were over 18 years old. The European Quality of
      Life Questionnaire--EQ-5D Version was used for evaluation of health-related
      quality of life. The self-assessement Zung-SDS was applied for evaluation of
      occurrence of depression. RESULTS: The statistical evaluation demonstrated that
      health-related quality of life (EQ-5D score and EQ-5D visual analogue scale)
      presents highly significant statistical dependence on sibutramine therapy (p <
      0.05). The statistical evaluation demonstrated that index of depression (SDS
      index) presents highly significant statistical dependence on sibutramine therapy
      (p < 0.05). CONCLUSION: The results show that sibutramine therapy has a highly
      positive effect on health-related quality of life among adult obese non-diabetic
      patients. Also, the results show that sibutramine therapy has a highly positive
      effect on occurence of depresion symptoms among adult obese non-diabetic patients
      (Fig. 2, Ref. 10).

PMID- 19750990
TI  - Pemphigus vulgaris: a 11-year review.
AB  - BACKGROUND: Pemphigus vulgaris (PV) is a rare, chronic life-threatening
      autoimmune blistering disease of the skin and mucous membranes. METHODS: A
      retrospective analysis of 31 patients with the diagnosis of pemphigus vulgaris,
      admitted for hospitalization from January 1996 to December 2006. Descriptive
      statistics has been used for data evaluation. RESULTS: The average age at onset
      was 49.0 +/- 16.2 years, with female to male ratio 1.4/1. Diagnosis was confirmed
      histologically and by a direct immunofluorescence. Mucocutaneous form of PV was
      observed in 25 patients (80.%), mucous form in 3 patients (9.7%), cutaneuos form
      in 3 patients (9.7%). Factors preceding the onset of PV were most often viral
      (38.7%) and bacterial (35.5%) infections, dental focuses (25.8%), stress (16.1%),
      and contact with chemical substances (16.1%). 6 patients (19.4%) did not indicate
      any triggering factor. Corticosteroids alone were given to 18 patients, combined
      with azatioprin or cyclosporin to 13 patients, and 1 patient was treated with
      intravenous immunoglobulin. Adverse events were mostly osteopenia/osteoporosis
      (41.9%), hyperlipoproteinemia (41.9%), cataract (32.3%) and Cushing's syndrome
      (32.3%). Cutaneous and mucous infections were most often caused by Staphylococcus
      aureus and Candida albicans, respectively. 3 patients died (9.7%), and in 3
      patients (9.7%) in a long term remission, the immunosuppressive treatment was
      discontinued. CONCLUSION: Pemphigus vulgaris is still a life-threatening disease.
      Although corticosteroids dramatically improved the mortality, and are still
      considered the first-choice therapy, significant morbidity of the disease and the
      corticosteroid treatment still exists. The combination of corticosteroids with
      corticosteroid-sparing agents delays the onset of adverse events (Fig. 2, Ref.
      33).

PMID- 19750991
TI  - Gastric adenocarcinoma and GIST (collision tumors) of the stomach presenting with
      perforation; first report.
AB  - Gastrointestinal stromal tumors are very rare tumors of stomach. To our knowledge
      there are a few reported cases of synchronous occurrence of epithelial and
      gastrointestinal stromal tumors of stomach. Also, tumor perforation is very rare.
      This is the first case of gastrointestinal stromal tumor synchronous with primary
      gastric adenocarcinoma presented with perforation (Fig. 1, Ref. 6).

PMID- 19750992
TI  - An appraisal of anatomy teaching and learning by undergraduate nursing students
      in a multiprofessional context: a study done at a medical school in South India.
AB  - AIM: This study was done to assess undergraduate nursing students' perception of
      the way anatomy is taught in a multiprofessional context. METHODS AND RESULTS:
      The study was done at Kasturba Medical College, Manipal University in India. The
      first year undergraduate nursing students were quantitatively and qualitatively
      appraised for their perception of the merits and demerits of the present anatomy
      curriculum. Questionnaires with close-ended and open-ended questions were
      distributed to the students. It was then statistically analyzed using the
      software package SPSS. A summative assessment of university examination results
      of the undergraduate students of the nursing course of the years 2005-2006 and
      2006-2007 were empirically compared. The students have rated the time allocated
      for anatomy teaching as insufficient. CONCLUSION: Nursing curriculum worldwide
      has undergone innovative changes bringing in newer methods of teaching and
      learning. It is high time that, the developing countries also follow in their
      wake and take up the issue of undergraduate nursing curricular reform. After
      recognizing the drawbacks of the present anatomy curriculum it's high time it is
      revised for undergraduate nursing student level (Tab. 5, Ref. 17).

PMID- 19750993
TI  - Sleep disordered breathing and arterial hypertension.

PMID- 19750994
TI  - Arthroscopic repair of delaminated acetabular articular cartilage in
      femoroacetabular impingement.
AB  - Lesions to articular cartilage can be difficult to treat and directly impact
      surgical outcome in hip arthroscopy. This article describes a direct cartilage
      suture repair technique for a young, active individual with full-thickness
      acetabular cartilage delamination. Lesions of this type are commonly seen with
      femoroacetabular impingement. A 17-year-old boy presented with bilateral hip pain
      greater in the right than left. Arthroscopic intervention for the right hip
      included direct cartilage repair for the cartilage lesion, osteoplasty for
      femoroacetabular impingement, repair for an anterior labral tear, capsular
      plication for iliofemoral ligament laxity, and psoas lengthening. Twelve weeks
      postoperatively, a standard capsular plication, osteoplasty, and chondroplasty
      were performed on the left hip. At follow-up, the patient reported feeling 95%
      normal. He noted that the right and left hips were essentially the same. Symptoms
      consisted of stiffness after prolonged sitting and mild pain following sports.
      The patient reported being pain free 90% of the time, with pain 2/10 at worst. He
      scored a 96 on the modified Harris Hip Score, 93 on the Hip Outcome Score
      Activities of Daily Living subscale, and 81 on the Hip Outcome Score Sports
      subscale. Overall, the patient was satisfied with the outcome. The direct
      cartilage repair, in addition to osteoplasty, anterior superior labral repair,
      iliofemoral capsular plication, and psoas lengthening, produced an excellent
      outcome in this young, active patient.

PMID- 19750995
TI  - Reconstruction of humeral head defect for locked posterior shoulder dislocation.
AB  - Locked posterior shoulder dislocation is a rare injury and is often missed on
      examination, usually due to inadequate imaging and potentially resulting in
      significant loss of shoulder function. An important feature of the physical
      examination is identification of the patient's inability to externally rotate
      their arm. These injuries are associated with defects in the humeral head
      articular surface, also known as reverse Hill-Sachs lesions. Medium-sized defects
      involving 25% to 50% of the articular surface can be reconstructed using several
      methods, including subscapularis or lesser tuberosity transfer, rotational
      osteotomy of the humerus, osteochondral autografting, and allograft
      reconstruction. We describe reconstruction of a 40% anteromedial humeral head
      articular surface defect associated with a missed locked posterior shoulder
      dislocation. Our technique used a deltopectoral approach with soft tissue
      dissection through the rotator interval to enable direct access to the defect
      with preservation of the rotator cuff muscles. The impacted articular surface was
      elevated, and the void was filled with moldable putty consisting of tricalcium
      phosphate with carboxymethylcellulose (Calstrux; Stryker Biotech, Hopkinton,
      Massachusetts). The articular fragment was then secured in position with size 5
      Ethibond (Ethicon, Inc, Somerville, New Jersey) bone sutures. The patient
      regained excellent function and range of motion, with computed tomography
      scanning at 9 months demonstrating a smooth humeral articular surface with
      excellent graft incorporation. This technique avoids donor site morbidity and
      potential risks with allograft use while maintaining normal shoulder joint
      anatomy with preservation of the rotator cuff muscles for less complicated
      prosthetic reconstruction if required in the future.

PMID- 19750996
TI  - Salmonella osteomyelitis in new-onset diabetes mellitus.
AB  - Salmonella species are rare bacterial isolates in osteomyelitis. This article
      describes a case of an otherwise healthy, active duty male military member with
      an insidious onset of right knee pain during a deployment to Kuwait. His work-up
      revealed an infectious process in the distal femur. Operative treatment and
      intravenous antibiotics resolved the infection. Intraoperative cultures revealed
      the rare isolate Salmonella enterica serotype C2 (Newport). Postoperative medical
      management revealed new-onset diabetes mellitus, possibly making this otherwise
      healthy host susceptible to this rare infection. Salmonella are gram-negative
      bacteria. Infection with nontyphoidal Salmonella species most commonly manifests
      as intestinal illness. Although it may be difficult for clinicians to accurately
      predict this rare entity as the causative organism in osteomyelitis, they may be
      aided by a history of travel to endemic regions or exposure to animal carriers.
      Comorbidities that seem to increase susceptibility include diabetes mellitus,
      human immunodeficiency virus, hemoglobinopathies, and immunosuppression. Blood
      cultures are reported to be frequently positive in cases of Salmonella
      osteomyelitis. Identification of Salmonella species from intraoperative cultures
      should prompt consultation with the infectious disease department for culture
      specific antibiotic tailoring. Many common antibiotic agents active against gram
      negative organisms seem efficacious. As in this case, following the basic tenets
      of osteomyelitis management should lead to an acceptable outcome.

PMID- 19750997
TI  - MRI measurement of the 2 bundles of the normal anterior cruciate ligament.
AB  - Anatomical studies have shown that the normal anterior cruciate ligament (ACL)
      consists of 2 distinct functional bundles: the anteromedial and posterolateral
      bundles. To date, no study has assessed the magnetic resonance imaging (MRI)
      appearance of the anteromedial and posterolateral bundles. The purpose of this
      study was to measure the anteromedial and posterolateral bundles using high-field
      digital MRI. Fifty MRIs of the knees of 50 patients were prospectively collected
      using a 1.5-T magnet. The length and width of each ACL bundle was measured on
      sagittal and coronal digital MRIs, independently performed by 2 observers blinded
      to each other's measurements. The average length and width of the anteromedial
      and posterolateral bundles were determined for all patients. Intraclass
      correlation coefficients were calculated to determine intertester test-retest
      reliability. In the sagittal plane, the anteromedial bundle averaged 36.9+/-2.8
      mm in length and 5.1+/-0.7 mm in width. The posterolateral bundle, by contrast,
      averaged 20.5+/-2.4 mm in length and 4.4+/-0.8 mm in width. In the coronal plane,
      the width of the anteromedial bundle averaged 4.2+/-0.8 mm and of the
      posterolateral bundle averaged 3.7+/-0.8 mm. Interobserver reliability for length
      of the ACL in the sagittal plane was 0.85, with a 95% CI of 0.75 to 0.91 for the
      anteromedial bundle and 0.75 with a 95% CI of 0.60 to 0.85 for the posterolateral
      bundle. Providing precise measurement of the ACL anteromedial and posterolateral
      bundles on MRI may improve the ability to detect damage to 1 or both of the
      bundles following injury.

PMID- 19750998
TI  - Intermediate outcomes after primary traumatic anterior shoulder dislocation in
      skeletally immature patients aged 10 to 13 years.
AB  - A paucity of literature exists regarding the outcome of skeletally immature
      patients who sustain a primary traumatic anterior shoulder dislocation. Most
      published results focus on adolescents and young adults, using recurrent
      dislocation/instability as a determinant of outcome, rather than a validated
      quality of life measurement tool. The purpose of this study is to assess the
      intermediate term functional outcome after anterior traumatic shoulder
      dislocation in the skeletally immature patient population. Fourteen patients (age
      range, 10.9-13.1 years; 14 shoulders) who sustained a primary anterior traumatic
      unidirectional shoulder dislocation were included. Each patient underwent
      successful documented closed reduction of the dislocated shoulder and was
      subsequently treated with initial nonsurgical intervention. All patients were
      monitored in the clinic routinely, until skeletal maturity was reached. The
      Western Ontario Shoulder Instability index (WOSI), range of motion,
      complications, and recurrent dislocations were recorded. The average WOSI score
      for all patients at the time of injury was 1635 (range, 1550-1690). At final
      follow-up (mean, 5.6 years), the average WOSI score for all patients was 39.6
      (range, 0-195). Subgroup analysis revealed that those treated nonoperatively
      fared better than their operative counterparts (average final follow-up WOSI
      score, 9.1 vs 151.7, respectively). Three patients (21.4%) ultimately sustained a
      recurrent shoulder dislocation that necessitated surgical intervention. Based on
      the above data, in the pediatric skeletally immature patient who sustained a
      primary, traumatic, anterior shoulder dislocation, nonoperative treatment results
      in low shoulder instability recurrence risk and sound functional outcomes.

PMID- 19750999
TI  - Radiation therapy for preventing recurrence of neurogenic heterotopic
      ossification.
AB  - Radiation therapy is commonly used to prevent heterotopic ossification, and the
      dose-dependent effects of this treatment have been well documented in patients
      after total hip arthroplasty (THA). However, the efficacy and dose requirement of
      radiation therapy to prevent heterotopic ossification of nonsurgical origin have
      not been studied. The purpose of this retrospective case-control study was to
      determine the effects of prophylactic radiation therapy on severe heterotopic
      ossification recurrence, postoperative range of motion (ROM), and wound healing
      in patients with heterotopic ossification secondary to neurologic deficits.
      Selection was not blinded, and higher risk patients were generally assigned to
      the treatment group. Standard doses of radiation therapy did not adequately lower
      recurrence rates; in fact, there was a higher incidence of heterotopic
      ossification formation necessitating revision in the treatment group (15.0%)
      compared to the control group (5.1%). Moreover, patients who received radiation
      therapy were not more successful at maintaining intraoperative ROM over time.
      There was a similar incidence of delayed wound healing between groups (12.8% in
      the control group and 12.5% in the treatment group), and no other negative side
      effects or complications were observed. These results suggest that the 700 cGy
      dose of radiation therapy typically used for the prophylaxis of heterotopic
      ossification associated with THA does not effectively prevent the recurrence of
      neurogenic heterotopic ossification in high-risk patients. Further studies are
      needed to determine whether higher doses of radiation therapy will provide more
      effective prophylaxis for heterotopic ossification.

PMID- 19751000
TI  - Unicompartmental knee arthroplasty to total knee arthroplasty conversion:
      assuring a primary outcome.
AB  - Converting unicompartmental knee arthroplasty (UKA) to total knee arthroplasty
      can be difficult, and specialized techniques are needed. Issues include bone
      loss, joint-line, sizing, and rotation. Determining the complexity of conversion
      preoperatively helps predict the need for augmentation, grafting, stems, or
      constraint. We examined insert thickness, augmentation, stem use, and effect of
      failure mode on complexity of UKA conversion. Fifty cases (1997-2007) were
      reviewed: 9 implants (18%) were modular fixed-bearing, 4 (8%) were metal-backed
      nonmodular fixed-bearing, 8 (16%) were resurfacing onlay, 10 (20%) were all
      polyethylene step-cut, and 19 (38%) were mobile bearing designs; 5 knees (10%)
      failed due to infection, 5 (10%) due to wear and/or instability, 10 (20%) for
      pain or progression of arthritis, 8 (16%) for tibial fracture or severe
      subsidence, and 22 (44%) due to loosening of either one or both components.
      Complexity was evaluated using analysis of variance and chi-squared 2-by-k test
      (80% power; 95% confidence interval). Insert thickness was no different between
      implants (P=.23) or failure modes (P=.27). Stemmed component use was most
      frequent with nonmodular components (50%), all-polyethylene step-cut implants
      (44%), and modular fixed-bearing implants (33%; P=.40). Stem use was highest in
      tibial fracture (86%; P=.002). Augment use was highest among all-polyethylene
      step-cut implants (all-polyethylene, 56%; metal-backed, 50%; modular fixed
      bearing, 33%; P=.01). Augmentation use was highest in fracture (86%) and
      infection (67%), with a significant difference noted between failure modes
      (P=.003). Failure of nonmodular all-polyethylene step-cut devices was more
      complex than resurfacing or mobile bearing. Failure mode was predictive of
      complexity. Reestablishing the joint-line, ligamentous balance, and durable
      fixation are critical to assuring a primary outcome.

PMID- 19751001
TI  - Extensor mechanism ruptures.
AB  - The extensor mechanism of the knee consists of the quadriceps muscle and tendon,
      the patella, the patellar tendon, and the tibial tubercle. Disruption of any of
      these can lead to an extensor mechanism rupture and render an otherwise perfectly
      good total knee replacement (TKR) useless. Quadriceps tears associated with TKR
      are difficult to treat and associated with a poorer prognosis than in the native
      knee. Transosseous sutures tied over the distal pole of the patella are
      recommended. Patella fractures may heal in continuity or may involve a disruption
      of the extensor mechanism. The blood supply may have been compromised during TKR,
      so healing may be delayed. The patella component may be loose and need to be
      removed or revised. Patellar tendon ruptures are the most common and serious form
      of extensor mechanism rupture. Prevention is more effective than treatment.
      Careful exposure during revision surgery includes anticipating the need for a
      quadriceps snip, pinning the tubercle to avoid avulsion, and preserving the fat
      pad during primary surgery. Treatment of patellar tendon ruptures is challenging.
      Primary repair may succeed in early intervention, but in established rupture,
      allograft reconstruction is often necessary. Achilles tendon allograft is
      preferred. The calcaneus fragment is embedded into the proximal tibia as a new
      tubercle, and the tendon is sutured into the remaining extensor mechanism. The
      repair is then protected using a cable loop from the superior pole of the patella
      to a drill hole in the upper tibia.

PMID- 19751002
TI  - Stiffness associated with total knee arthroplasty.
AB  - Multiple factors may lead to stiffness after total knee arthroplasty (TKA),
      including patient diagnosis, preoperative range of motion (ROM), prosthetic
      geometry used, surgical technique, intraoperative ROM after capsular closure,
      postoperative rehabilitation, and wound healing factors. An ipsilateral arthritic
      hip can also inhibit postoperative recovery and lead to knee stiffness. Exposure
      of the ankylosed knee can be difficult. One must take care to avoid excessive
      stress on the patellar tendon insertion leading to patellar tendon avulsion. The
      2 most common methods to facilitate exposure are a proximal release or a tibial
      tubercle osteotomy. When patients fail to achieve satisfactory ROM after TKA,
      manipulation under anesthesia is considered. It is usually performed
      approximately 6 weeks postoperatively. The best indicator of each patient's
      potential is his or her intraoperative flexion against gravity with the capsule
      closed at the end of the procedure.

PMID- 19751003
TI  - Malalignment: forewarned is forearmed.
AB  - Malalignment in total knee arthroplasty (TKA) is a major source of failure.
      Concern exists as to the acceptable window for overall coronal alignment in TKA.
      We evaluated the anatomical coronal alignment of 6070 primary TKAs using standard
      length knee radiographs. The mean postoperative alignment was 4.8 degrees of
      valgus, with 1 standard deviation within the mean defining a range of 2.4 degrees
      to 7.2 degrees of valgus. The revision rate not related to infection for this
      well-aligned group was 0.5% (3 degrees =0.47%; 4 degrees =0.54%; 5 degrees
      =0.47%; 6 degrees =0.39%; 7 degrees =0.62%). In comparison, the failure rate for
      TKAs aligned in relative varus (<2.4 degrees of valgus) was 1.8% (P=.0004) and
      for those in valgus (>7.2 degrees of valgus) was 1.5% (P=.0027). Kaplan-Meier
      survival analysis confirmed these findings. The failure rates were statistically
      higher for the valgus and varus groups, compared to the well-aligned group within
      1 standard deviation of the mean. Moreover, varus-aligned knees failed primarily
      by medial tibial collapse, whereas valgus-aligned knees failed because of
      ligamentous laxity. Restoring coronal alignment to between 2.4 degrees and 7.2
      degrees of anatomical valgus is the most important surgeon-controlled factor in
      TKA.

PMID- 19751004
TI  - Seven cuts to the perfect total knee.
AB  - There are a total of 7 bone cuts in a typical total knee replacement (TKR):
      distal femur, anterior femur, posterior femur, anterior chamfer, posterior
      chamfer, tibia, and patella. Each of these cuts has its own special science, and
      each cut can affect the other cuts and potentially the outcome of the TKR. The
      distal femoral cut starts the overall alignment of the leg. Five degrees of
      valgus is cosmetically appealing, avoids excessive valgus, and prevents thighs
      from rubbing together. The anterior femoral cut sets femoral component rotation,
      which has effects on patellar tracking and gap balancing. In most knees, correct
      rotation is approximately 3 degrees of external rotation compared to the
      posterior condylar axis. An important exception is in valgus knees, where this
      could lead to accidental internal rotation. The posterior condyle cuts, with the
      tibial cut, determine the flexion gap. Injury to the medial collateral and
      posterior cruciate ligaments should be avoided. Anterior and posterior chamfer
      cuts must avoid these ligaments as well. The tibial cut is challenging. A 3
      degrees posterior slope is most typical, and rotation is crucial. Internal
      rotation is a common error, affecting patellar tracking. Changing rotation on a
      sloped cut also adds varus or valgus. The patella cut should not be too deep.
      Component placement should tend medial and superior. If a lateral release is
      necessary, it should be done from inside-out, with preservation of the blood
      supply.

PMID- 19751005
TI  - Computer-assisted TKA: greater precision, doubtful clinical efficacy: opposes.
AB  - Despite improved precision of component placement and consistent and accurate
      restoration of neutral limb alignment, controversy persists regarding the
      clinical benefits of computer-assisted total knee arthroplasty (TKA). Computer
      assisted TKA provides excellent information regarding gap equality and symmetry
      throughout the knee range of motion and allows precise, quantitative soft tissue
      release for deformities, especially in knees with severe flexion contractures and
      severe rigid valgus deformities. Hence accurate restoration of gap balance, joint
      line, and posterior femoral offset consequently improves functional results. Knee
      arthritis with complex extra-articular deformities and in situ hardware can be
      tackled appropriately using computer navigation where conventional techniques may
      be inadequate. It also allows intra-articular correction for extra-articular
      deformities due to malunions and facilitates extra-articular correction in cases
      with severe extra-articular tibial deformities. In obese patients, where the
      alignment of the limb is difficult to assess, computer navigation improves
      accuracy and reduces the number of outliers. The ability to quantify the precise
      amount of bone cuts and soft tissue releases needed to equalize gaps and restore
      alignment, reduced blood loss, and incidence of systemic emboli improves the
      safety of the procedure and hastens functional recovery of the patient. Hence,
      computer-assisted TKA not only provides greater precision, but also greater
      clinical benefit.

PMID- 19751006
TI  - Computer-assisted TKA: greater precision, doubtful clinical efficacy: affirms.
AB  - Component and limb alignment are essential surgical variables that influence the
      long-term performance of a total knee arthroplasty (TKA). Total knee arthroplasty
      failure remains multifactorial, and computer-assisted surgical techniques may
      address only part of the failure pathophysiology. Despite attempting to use
      computer-assisted surgical techniques to improve TKA alignment, recent evidence
      has reported that the entire nature of the computer-assisted experience is not
      particularly forgiving, as significant increases in time and complications remain
      problematic. It appears computer-assisted surgical techniques are not yet "ready
      for primetime" with reproducible and proven long-term benefits for patients.
      Further studies are needed to better determine the precise target toward which to
      aim computer-assisted surgery efforts.

PMID- 19751007
TI  - Extra-articular deformity is always correctable intra-articularly: to the
      contrary.
AB  - The operative word in this debate is "always." In my opinion, there are some
      cases better served by extra-articular correction. The question then becomes
      which ones, and how does the surgeon determine? There are 4 considerations: the
      magnitude of the deformity, the relationship of the deformity to the knee, the
      side of the deformity (varus or valgus), and whether the femur or the tibia is
      affected by the deformity. A larger deformity is more important, but just as
      important is its relationship to the knee. Large deformities distant to the knee
      have little impact on the knee. Varus deformities require lateral intra-articular
      overresection, which produces lateral instability. Valgus deformities require
      medial overresection, which produces medial instability. Lateral instability is
      stabilized by the dynamic lateral stabilizers (popliteus, lateral head of the
      gastrocnemius, biceps femoris, and iliotibial tract) and is better tolerated than
      medial instability. The best way to determine the consequence of the malalignment
      in question is to template the knee by drawing the mechanical axis from the
      femoral head or ankle to the center of the knee, and then the resection level
      that will be required. This will demonstrate the amount of overresection required
      to correct the extra-articular deformity, and in some cases will indicate the
      advantage of an extra-articular correction.

PMID- 19751008
TI  - Extra-articular deformity is always correctable intra-articularly: in the
      affirmative.
AB  - Patients with arthritis of the knee and an extra-articular deformity present a
      unique technical challenge, as it becomes more difficult to restore the
      mechanical axis during total knee replacement (TKR). Current treatment options
      include a 2-stage procedure in which an extra-articular correctional osteotomy is
      performed several months before the primary TKR, a 1-stage procedure in which an
      extra-articular correctional osteotomy is performed at the time of the index TKR,
      or a 1-stage procedure in which TKR is performed with correction of the extra
      articular deformity. One-stage TKR with intra-articular correction of the extra
      articular deformity is our treatment of choice. With proper planning, appropriate
      bone cuts to restore alignment, and the necessary soft tissue releases to balance
      the knee in flexion and extension, a satisfactory TKR can be achieved. Two
      patients with arthritis and a severe extra-articular deformity (varus/valgus
      deformity >20 degrees , recurvatum and malunion of a tibial or femoral fracture)
      were treated with 1-stage TKR with intra-articular correction of the extra
      articular deformity. The technique followed had been successfully performed in 15
      previous cases. The procedure was clinically successful in both patients without
      complications. At 2-year follow-up, Knee Society Scores improved from 40 to 95
      and there was no evidence of instability in either case.

PMID- 19751009
TI  - The role of impaction grafting: the when and how.
AB  - The challenges of acetabular revision include bone loss and poor bone biology.
      Favorable 10-year reports exist of uncemented acetabular revision using
      hemispherical uncemented sockets. In the presence of bone stock deficiency,
      adjunctive morsellized impaction bone grafting is a recognized means of restoring
      bone stock. We attempt to restore bone stock with impaction grafting beneath a
      cementless cup for contained defects, defects that can be rendered contained, and
      whenever there is capacity for rim fixation. The technique of bone graft
      preparation is important. We use a mixture of bone milling and bone chips of
      various sizes. Morsellized allograft is inserted, packed, and/or reverse reamed
      into any defects. The reconstruction relies on the ability to gain biological
      fixation of the component to the underlying host bone. This requires intimate
      host bone contact and rigid implant stability. The fixation is therefore
      augmented with screws in all cases. It is important to achieve host bone contact
      in a least part of the dome and posterior column. When this is possible, and
      particularly when there is a good rim fit, we have not found it absolutely
      necessary to have contact with host bone over >50% of the surface. Stability of
      primary fixation is a better predictor of outcome than volume of graft or
      percentage of host bone contact. The advantages of bone grafting in acetabular
      reconstruction include the ability to restore bone stock, rebuild a normal hip
      center and hip biomechanics, and increase bone stock for future revisions.

PMID- 19751010
TI  - Algorithmic approach for reconstruction of proximal femoral bone loss in revision
      total hip arthroplasty.
AB  - Reconstruction of the femur depends on the quantity of bone loss and the quality
      of the remaining bone stock. Multiple classifications and reporting systems can
      be used to characterize the bone defect. We present a simple algorithmic approach
      for proximal femoral bone loss reconstruction during revision total hip
      arthroplasty. Quantity of bone loss is assessed using radiographs based on
      different classification systems, whereas quality of the remaining bone stock is
      assessed intraoperatively. Based on the type of proximal bone loss and the
      quality of the available bone, we describe our preferred reconstruction
      technique. For minor bone loss, the metaphysis is expanded but intact with
      partially absent calcar. There is minimal bone loss anteriorly and posteriorly,
      and the diaphysis is intact. For significant bone loss, the metaphysis is
      compromised, and there is no calcar. There is minimal bone loss anteriorly and
      posteriorly. The available proximal bone may be thin, sclerotic, and incapable of
      support. However, the diaphysis is intact. For massive bone loss, there is
      complete circumferential bone loss in the metaphysis, extending to the diaphysis.
      The anterolateral bone and supporting subtrochanteric metaphyseal bone are
      absent. The metaphysis is not stable and will not offer rotational stability.
      There is massive bone loss anteriorly and posteriorly. The stability of the
      implant is dependent on distal diaphyseal fixation. For complete proximal bone
      loss, there is extensive circumferential segmental bone loss proximally and
      extensive cavitary loss involving the entire diaphysis. Additionally, there is
      extensive ectasia of the diaphysis.

PMID- 19751011
TI  - Shell retention with a cemented acetabular liner.
AB  - The authors reviewed the indications, technique, and results of cementing an
      acetabular liner into a well-fixed cementless acetabular shell. Indications for
      this procedure include a worn acetabular liner in a well-fixed cementless
      acetabular shell as well as an unstable total hip construct where the shell is
      secured. To perform such a procedure, an adequate shell diameter is necessary to
      accept an acetabular liner that will enable 2 mm of cement mantle around it. If
      the shell has screw holes, there is no need to score the acetabular shell, but
      otherwise the acetabular shell must be scored to a 1-mm depth in a spiderweb
      configuration. As for the acetabular liner, it too must be scored to a 1-mm depth
      in a spiderweb configuration (which enhances torsional stability) as well as a
      circular configuration to provide optimal lever-out strength. We have evaluated
      31 constrained liners and 30 nonconstrained liners with this preparation. The
      failure rate in the constrained liner series was 6%, and no failures occurred in
      the nonconstrained series. One dislocation occurred in the nonconstrained series
      where patients were typically placed in a brace or cast for 6 weeks. This option
      should be considered in cases with worn-through acetabular liners for unstable
      configurations when the acetabular shell is well fixed and is of adequate
      diameter to accept such a construct.

PMID- 19751012
TI  - Cement mantle retention: filling the hole.
AB  - Revision total hip surgery requires a number of techniques that optimizes
      outcomes while minimizing bone loss. One such technique that has proven useful in
      revision of the femoral components in revision total hip surgery is leaving an
      intact cement mantle in place and cementing a new prosthesis within the intact
      cement mantle. Careful patient selection and preoperative planning are essential
      for the successful implementation of this technique. The appropriate indications
      are: (1) if the original stem is broken, but the cement mantle is intact, (2)
      when removing a well-fixed, cemented stem to improve exposure for an acetabular
      revision, increase femoral offset, or femoral head diameter, and (3) when
      removing a debonded femoral component. Although the cement-within-cement revision
      technique is rarely used, it is an important technique to have in your portfolio.
      However, it is also important to keep in mind some of the drawbacks of cement
      within-revisions and to consider these factors when deciding whether this
      technique is appropriate for a specific patient.

PMID- 19751013
TI  - Long-term outcome of shelf grafts in total hip arthroplasty for developmental hip
      dysplasia.
AB  - Primary total hip arthroplasty (THA) in patients with osteoarthrosis secondary to
      developmental hip dysplasia is often complex due to anterolateral acetabular bone
      deficiency. The use of femoral head (shelf) autograft during the index
      arthroplasty provides nonimmunogenic, osteoconductive support with the potential
      for enhanced bone stock should revision surgery be required. Few long-term
      studies document the outcome of the use of shelf grafts in primary THA or
      quantify the need for further bone graft at revision surgery. A retrospective
      analysis was conducted of a single surgeon's series of 31 THAs performed in 25
      patients with developmental hip dysplasia. Postoperative biplanar radiographic
      analysis was performed at 3 and 6 months and annually thereafter for a mean of 14
      years (range, 8-18 years). Grafts were assessed for union, resorption, and
      displacement. The need for acetabular bone graft at revision surgery was
      recorded. Bony union was observed in 93% of cases; fibrous union developed in the
      remaining 7%. There was no graft displacement. In 71% of cases, less than one
      third of the graft had resorbed; one-third to one-half had resorbed in the
      remaining 29% of cases. Of 10 patients revised (all for loosening of the
      acetabular component), 2 required structural allograft for inadequate bone stock.
      Femoral head autograft allows effective acetabular coverage with excellent rates
      of union, exhibits minimal graft resorption in the long-term, and rarely requires
      further acetabular allograft in revision surgery.

PMID- 19751014
TI  - The dislocator, early and late: the role of large heads.
AB  - Dislocation after total hip arthroplasty (THA) is a potentially devastating
      complication that can be difficult to manage. Many patient and mechanical factors
      have been associated with an increased risk of dislocation. Conservative
      treatments such as abduction bracing have not proven effective at treating this
      difficult problem. Surgical options include the use of larger femoral heads,
      unconstrained tripolar femoral heads, and constrained devices. While each device
      has its merits, there is no one-size-fits-all solution to this problem. With the
      development of highly cross-linked polyethylene and its superior wear
      characteristics and mechanical properties, the use of larger femoral heads is now
      available. Twenty-six hips in 25 patients who underwent revision surgery for
      recurrent dislocation were treated with a femoral head =/>36 mm in diameter. The
      direct lateral surgical approach was used in 24 hips, and the posterior and
      anterior supine intermuscular approaches were used in 1 hip each. One patient
      died 5 years after revision surgery, and 3 patients have not returned for
      clinical follow-up over the past 2 years. Four hips subsequently suffered a
      repeat dislocation, for a dislocation rate of 17%. Two patients underwent a
      subsequent surgery: 1 irrigation and debridement and 1 hardware removal. There
      have been no other revisions to date. Mean time to follow-up is 17.2 months.
      While the use of large femoral heads for the treatment of dislocation is
      warranted, continued follow-up is necessary.

PMID- 19751015
TI  - Total hip arthroplasty in acetabular protrusio.
AB  - Protrusio is a central acetabular defect resulting from migration of the femoral
      head medial to Kohler's line. Protrusio can develop in association with a number
      of conditions that affect the metabolism or mechanical behavior of the
      periacetabular bone. Total hip arthroplasty (THA) for acetabular protrusio
      requires reconstruction of the contained cavitary defect. The acetabular rim is
      generally intact. The defect can be effectively treated with a lateralized
      cementless porous-coated component supported on the peripheral acetabular bony
      rim. Morsellized autograft is used to fill the medial defect. However, if the rim
      is inadequate to provide mechanical support for a cementless cup due to bone loss
      or osteoporosis, cementless cup reconstruction can result in medial migration. If
      rim support is inadequate, a reconstruction cage is a more appropriate option to
      gain fixation to the pelvis above and below the acetabulum. Total hip
      arthroplasty for protrusio can also affect both offset and leg length, so careful
      preoperative templating is important to help determine implant position. Results
      of THA with medial acetabular bone grafting for protrusio acetabuli have been
      favorable, with success rates similar to conventional THA.

PMID- 19751016
TI  - Periprosthetic fractures of the femur.
AB  - Treatment of periprosthetic femur fracture is based on fracture timing, implant
      stability, fracture pattern, and bone quality. Intraoperative fractures are
      usually stable; to prevent intraoperative fracture, careful preoperative planning
      and gentle operative techniques are essential. In managing unstable
      intraoperative and late postoperative periprosthetic fractures, the surgeon
      should be know the exact pattern of fracture, prosthesis stability, and bone
      quality. Loose prostheses should be revised and displaced fractures should be
      reduced and adequately fixed. These fractures typically occur in the
      peritrochanteric area, and their treatment is cerclage wiring or cables.
      Postoperative periprosthetic fractures are usually the result of trauma in the
      setting of loosening of the prosthesis and/or osteolysis. Periprosthetic femoral
      fractures are classified using the Vancouver classification, which is based on
      the location of the fracture, the amount of available proximal bone stock, and
      the stability of the stem. Correct classification of these fractures is
      important, as it helps to guide treatment.

PMID- 19751017
TI  - Acetabular options: notes from the other side.
AB  - The socket remains the weakest link of primary total hip arthroplasty (THA). The
      revision rates of the socket are higher than those of the stem, with aseptic
      loosening and polyethylene wear being the most frequent indications for revision
      THA. Both cemented all-polyethylene cups and cementless sockets have benefited
      from stepwise improvements in surgical techniques and designs. In many countries,
      cementless sockets have replaced cemented cups during primary THA, with >90% of
      the acetabular components using a cementless fixation mode. The long-term
      prospective data of cementless sockets from high-volume centers show excellent
      and equivalent survivorship to cemented implants, but the insertion technique is
      easier and quicker. In addition, cementless sockets are more versatile than
      cemented all-polyethylene cups. With cementless sockets there is a move to
      increased porosity of the ingrowth surface, tri-bearing options, and enhanced
      locking mechanisms. There is a role for well-conducted randomized controlled
      trials to assess these new designs because data from various national registries
      show that the socket remains the weakest link of primary THA. Factors like sex,
      age, diagnosis, and bearing couples have a different and significant influence on
      the intermediate to long-term survivorship of contemporary cemented and
      cementless THA.

PMID- 19751018
TI  - A short stem solution: through small portals.
AB  - While short stem design in total hip arthroplasty (THA) is not a new concept,
      interest has surged with the increasing popularity of less invasive techniques.
      Given the success of traditional stems, why consider short stems? Several reasons
      exist. If the goal of the tapered stem is to load preferentially proximally,
      achieve tight fit, and deliver stresses into proximal bone, do we need a stem at
      all? While long stems may prevent varus malalignment, varus malalignment of
      tapers does not impair results. Short stems are easier to insert, especially when
      using an anterior approach. Femoral preparation is accomplished with
      straightforward broaching without reamers. Short stems are bone conserving,
      violating less bone stock and providing more favorable conditions should revision
      be required. As with any novel device, longer follow-up is needed to fully assess
      shortened tapered stems. However, our early results in 640 primary THAs at up to
      38 months are promising. Usually 1 or 2 diameter sizes larger are required with
      the short vs standard length version of the same tapered design. Be aggressive
      with sizing, pushing to the largest possible. Use the broach like a rasp. Drive
      the component in valgus during insertion. Upon seating, do a trial reduction
      using the shortest available neck length. The component generally sits slightly
      prouder than the broach and may require additional effort to seat completely.

PMID- 19751019
TI  - Cemented femoral fixation: the North Atlantic divide.
AB  - European nations, especially Scandinavian countries, have used cemented fixation
      since the introduction of total hip arthroplasty. In Sweden, with arguably the
      best national-level data on prostheses survivorship, >90% of all stems are
      fixated with cement. In sharp contrast, it is estimated that in the United
      States, >88% of all femoral stems use cementless technology. This represents a
      diametrically opposed difference in philosophical approach: the so-called North
      Atlantic Divide. The departure in North America from cemented femoral stems can
      be traced to the coinage of the phrase "cement disease," which implicated cement
      as a leading cause of osteolysis. This led to prolific innovation of uncemented
      technologies in North America, while European countries favored standardization
      enabled by the national arthroplasty registries. The term "cement disease" has
      been proven to be a misnomer, as supported by excellent outcomes from the
      Scandinavian registries, as well as excellent long-term outcomes for cemented
      stems in United States series, even in patients younger than 50 years. Like
      uncemented stems, there is variability in survivorship between femoral stems, and
      this appears to be related to specific design features. Despite the excellent
      long-term results, the use of cemented femoral components in Europe and Canada is
      decreasing in favor of uncemented stems. The reasons for this are not immediately
      obvious.

PMID- 19751020
TI  - Metal-metal bearing surfaces in hip arthroplasty.
AB  - There is no mystery regarding the allure of metal-metal bearings: high stability
      and low wear potential. The special risks associated with these bearings are
      coming into focus and include a macrophage response to excessive metal particles
      (metal reactivity) and a lymphocyte-dominated reaction (metal sensitivity). The
      most common presentation of an adverse local tissue reaction (ALTR) is persistent
      pain. The incidence of ALTR has not been completely defined, but the risk appears
      to be increased in resurfacing, in women, and in bilateral cases. The
      differential diagnosis includes septic and aseptic loosening, and the evaluation
      should include aspiration. The diagnosis is confirmed by histological
      examination.

PMID- 19751021
TI  - Antibiotic bone cements: their use in routine primary total joint arthroplasty is
      justified.
AB  - The use of antibiotic bone cement in total hip arthroplasty (THA) is the standard
      of care in countries with long-standing national registries, as data from the
      registries demonstrates an improvement in survivorship by reducing the incidence
      of both septic and aseptic failures. There is reluctance in North America to
      embrace antibiotic bone cement, although the percentage of use is increasing.
      Reasons cited for not using antibiotic cement include lack of efficacy, adverse
      effects on mechanical properties, increased costs, bacterial resistance, and
      systemic toxicity. Little to no compelling data in the literature support these
      claims, and significant evidence refutes them, specifically: registry data and
      randomized controlled trials demonstrate a clear reduction in deep joint
      infections with the use of antibiotic bone cement; antibiotic bone cement has
      lower incidence of both septic and aseptic loosening, indicating no negative
      effect on mechanical properties; antibiotic bone cement is cost-effective, given
      its proven ability to reduce revision rates and prevent poor patient outcomes;
      there is no evidence to support bacterial resistance, and antibiotic bone cement
      may reduce the incidence of resistance; and there are no reported cases of
      systemic toxicity from manufacturer-prepared antibiotic cement in primary THA or
      total knee arthroplasty. Based on the strong evidence supporting the benefits of
      antibiotic bone cement and the lack of evidence against its use, it is difficult
      to justify why antibiotic cement is not the standard of care for primary cemented
      THA in North America.

PMID- 19751022
TI  - Precision surgery.
AB  - Accurate component placement in joint replacement cannot be overemphasized;
      despite many re-engineering efforts over the past 3 decades, failure rates at 10
      years for total hip arthroplasty (THA) and total knee arthroplasty (TKA) remain
      constant. Intraoperative decisions with joint replacement have been facilitated
      with manual instrumentation and are affected by the surgeon's intuition,
      instinct, and experience. Current technology allows the development and use of
      high-tech instrumentation, which, irrespective of surgeon-dependent variables,
      gives intraoperative quantitative information on which precise placement of hip
      and knee components can be done. Component placement is the single most important
      technical maneuver the surgeon accomplishes to prevent mechanical complications,
      which will nearly eliminate outliers from very good and excellent results and
      revision as a consequence of technical errors; computer navigation has almost
      made it possible. In knees it gives precise component placement in the coronal
      and sagittal planes, and in hips it particularly improves acetabular component
      position by numerical control of inclination, anteversion, and most importantly
      center of rotation. Precision is enhanced even more when computer navigation is
      elevated to the next level, which is robotic guidance. The preoperative plan set
      by the surgeon is executed by the robotic tool while the surgeon manually
      controls the robotic arm. Bone preparation cannot exceed the boundaries the
      surgeon has set, as the surgeon's manual force will stop the robot and the error
      cannot be made. Robotic surgery has progressed in the unicompartmental knee, and
      this innovation is in the final stages of development in THA.

PMID- 19751023
TI  - Internet access produces misinformed patients: managing the confusion.
AB  - The Internet has produced a truly phenomenal increase in access to information.
      This is really only helpful to patients if the information is filtered and
      appropriate to their specific needs. Too often patients access information about
      conditions they have self-diagnosed and bring it to the consultation with their
      physician, who then has to spend time disabusing the patients of the
      misinformation they have accumulated. Patients also return home from their
      initial consultation, access the Internet, and come up with all manner of
      promotional information from companies and even orthopedic practices that they
      want explained to them by their physician. It is the overwhelming conclusion of
      orthopedic specialists that this kind of Internet use is actually a burden for
      them in caring for patients and is not contributing to patient enlightenment. It
      does not have to be this way, if physicians will do just 2 things: first, create
      white papers for patients that address common current questions, such as surgical
      approach or bearing surfaces for implants and why we do what we do. This is a
      huge time saver and will preempt many questions. Second, develop their own
      website or select excellent nonprejudicial sites to which they can refer
      patients. To do less will invite a neverending parade of questions irrelevant to
      patient welfare.

PMID- 19751024
TI  - Current controversies in critical illness-related corticosteroid insufficiency
      and glucocorticoid supplementation.
AB  - The stress response, which is triggered by a number of factors, including
      surgery, results in activation of the hypothalamic pituitary adrenal axis and
      subsequent release of cortisol from the adrenal glands. Critical illness-related
      corticosteroid insufficiency is an inadequate corticosteroid response relative to
      a patient's illness; patients with critical illness-related corticosteroid
      insufficiency have both insufficient circulating cortisol and impaired cellular
      use of glucocorticoids. Corticosteroids, such as hydrocortisone, have been cited
      to improve survival, oxygenation, duration of mechanical ventilation, and
      intensive care unit-free days in critically ill patients. Perioperative
      glucocorticoid supplementation is also recommended in patients with secondary
      adrenal insufficiency due to chronic corticosteroid use.

PMID- 19751025
TI  - Performance-enhancing drug use.
AB  - According to Gary Green, MD, everyone who deals with athletes is a "stakeholder"
      in the issue of performance-enhancing drugs and can influence athletes in a
      positive or negative role. In this issue of ORTHOPEDICS, Dr Green shares his
      thoughts on testing, prevention, and education of performance-enhancing drug use.

PMID- 19751026
TI  - Arthroscopic visualization of subscapularis tendon lesions.
AB  - Certain lesions of the subscapularis tendon are difficult to identify during
      routine shoulder arthroscopy due to the fact that complete visualization of the
      tendon's insertion on the lesser tuberosity can be challenging. This article
      describes a maneuver used during shoulder arthroscopy that provides excellent
      visualization of the subscapularis tendon insertion on the proximal humerus. This
      technique is advantageous because (1) it allows for complete visualization of the
      intra-articular tendinous insertion of the subscapularis using a standard 30
      degrees arthroscope inserted through the standard posterior portal and (2) it
      facilitates the use of standard transrotator interval portals for tendon
      debridement, suture passage, or implant insertion without the need for accessory
      portals.

PMID- 19751027
TI  - Current concepts in joint replacement.

PMID- 19751028
TI  - Your diagnosis? Failed total knee arthroplasty with dislocated rotating platform
      polyethylene component.

PMID- 19751030
TI  - Working with the "right people" and the "wrong people".

PMID- 19751031
TI  - Cell phone communication with patients: love it or hate it?

PMID- 19751032
TI  - Cell phone communication with patients: love it or hate it?

PMID- 19751033
TI  - The feds and EHRs.

PMID- 19751034
TI  - Dr. Starfield brings it home.

PMID- 19751035
TI  - Dr. Starfield brings it home.

PMID- 19751036
TI  - ICD-9 2010: new and noteworthy codes.

PMID- 19751037
TI  - Five communication strategies to promote self-management of chronic illness.

PMID- 19751038
TI  - Immediate action protocol: a tool to help your practice assess suicidal patients.

PMID- 19751039
TI  - What you can do to help your uninsured patients.

PMID- 19751040
TI  - Offering financial assistance to newly uninsured patients.

PMID- 19751049
TI  - Are you thinking right?

PMID- 19751050
TI  - Analyte concentration at the tip of a nanopipette.
AB  - Concentration of molecules within the tips of nanopipettes when applying a DC
      voltage is herein investigated using finite-element simulations. The ion
      concentrations and fluxes due to diffusion, electro-migration, and electro
      osmotic flow, and the electric potential are determined by the simultaneous
      solution of the Nernst-Planck, Poisson, and Navier-Stokes equations within the
      water solution containing sodium and chloride ions and negatively charged
      molecules. The electric potential within the pipette glass wall is at the same
      time determined by the Poisson equation together with appropriate boundary
      conditions and accounts for a field effect through the wall. Fixed negative
      surface charge on both the internal and external glass surfaces of the
      nanopipette is included together with the field effect through the glass wall to
      account for the electric double layer and the electro-osmosis. The inclusion of
      the field effect through the pipette wall is new compared to previous modeling of
      similar structures and is shown to be crucial for the behavior at the tip. It is
      demonstrated that the concentration of molecules is a consequence of ionic charge
      accumulation at the tip screening the electric field, thereby slowing down the
      electrophoretic motion of the molecules, which is further slowed down or stopped
      by the oppositely directed electro-osmosis. It is also shown that the trapping is
      very sensitive to the properties of the molecule, that is, its electrophoretic
      mobility and diffusion coefficient, the properties of the pipette, the ionic
      strength of the solution, and the applied electric field.

PMID- 19751051
TI  - Imaging of lipids in spinal cord using intermediate pressure matrix-assisted
      laser desorption-linear ion trap/Orbitrap MS.
AB  - A hybrid linear ion trap/Orbitrap mass spectrometer was used to perform tandem
      mass spectrometry (MS/MS) experiments and high-resolution mass analysis of lipids
      desorbed from nerve tissue. A dramatic improvement in mass spectral resolution
      and a decrease in background are observed in the spectra collected from the
      Orbitrap mass analyzer, which allows generation of more accurate mass
      spectrometric images of the distribution of lipids within nerve tissue.
      Employment of both mass analyzers provides a rapid and reliable means of compound
      identification based on MS/MS fragmentation and high-resolution mass spectrometry
      (HRMS) accurate mass.

PMID- 19751052
TI  - Facile and controllable loading of single-stranded DNA on gold nanoparticles.
AB  - A facile strategy of loading thiolated single-stranded DNA (ss-DNA) on gold
      nanoparticles (NPs) has been developed. The gold NPs stabilized by nonionic
      fluorosurfactant (i.e., Zonyl FSN) are simply mixed with the thiolated ssDNA in
      the presence of NaCl (up to 1.0 M), and the ssDNA-NP conjugates are attained
      after an incubation of 2 h. The loading density of the ssDNA is controlled by the
      salt concentration in the immobilization solution. The FSN capping layer inhibits
      effectively the nonspecific adsorption of nucleobases on the NPs but allows for
      rapid attachment of the thiolated ssDNA through the sulfur-gold linkage, which
      may lead to an upright orientation of the immobilized ssDNA. The maximum loading
      density of the ssDNA obtained in 1.0 M NaCl is sensitive to several factors, such
      as the type of the spacer, the length of the ssDNA strands, and the NP size. The
      hybridization behavior of the ssDNA-NP conjugates with complementary ssDNA in
      solution was examined. For the conjugates of 13 nm-diameter NPs, the
      hybridization efficiency can reach approximately 60% when the surface density of
      the ssDNA on the gold NP is lower than approximately 15 pmol/cm(2). As the ssDNA
      probes are more densely packed on the NPs, the hybridization efficiency drops
      consequently.

PMID- 19751053
TI  - Inter- and intramolecular addition reactions of electron-deficient alkenes with
      alkyl radicals, generated by SET-photochemical decarboxylation of carboxylic
      acids, serve as a mild and efficient method for the preparation of gamma-amino
      acids and macrocyclic lactones.
AB  - Inter- and intramolecular additions of alkyl radicals, generated by SET
      photochemical decarboxylation reactions of free carboxylic acids, to electron
      deficient alkenes take place under mild conditions as part of efficient routes
      for the formation of N-Boc gamma-amino acids and macrocyclic lactones.

PMID- 19751054
TI  - Solvation structures of cis- and trans-1,2-dichloroethylene in supercritical CO2
      investigated by Raman spectroscopy and attractive energy calculations.
AB  - Vibrational Raman spectra of the C horizontal lineC stretching modes of cis- and
      trans-1,2-dichloroethylene (C(2)H(2)Cl(2)) were measured in supercritical carbon
      dioxide (CO(2)). The spectra were collected at a fixed solute mole fraction by
      varying the fluid density by a factor of 20. As the density increased, the peak
      frequencies of the C horizontal lineC stretching modes shifted toward the low
      energy side at isotherms of reduced temperature, T(r) = T/T(c) = 1.02, 1.06, and
      1.20. By analyzing these density dependences using the perturbed hard-sphere
      theory, we decomposed the shifts into attractive and repulsive components. The
      repulsive shifts of cis-C(2)H(2)Cl(2) were almost equivalent to those of trans
      C(2)H(2)Cl(2). However, the attractive shifts of nonpolar trans-C(2)H(2)Cl(2)
      were significantly greater than those of polar cis-C(2)H(2)Cl(2) at all densities
      and temperatures. To evaluate the difference in the isomers, we calculated the
      attractive shifts of the C horizontal lineC stretching modes of each isomer,
      composing of dispersion, dipole-induced-dipole, and dipole-quadrupole
      interactions between solute C(2)H(2)Cl(2) and solvent CO(2) molecules. These
      three interactions were quantified by considering molecular configurations and
      orientations, and solvation structures around the isomers were elucidated by 3D
      schematic diagrams. As a result, it was shown that the anisotropic solvation
      structure around trans-C(2)H(2)Cl(2) was responsible for the larger attractive
      shifts in the supercritical CO(2). The difference of solvation structures between
      the isomers was significant at T(r) = 1.02 but became minor as the temperature
      increased to T(r) = 1.20.

PMID- 19751055
TI  - Strategies for increasing the efficiency of heterojunction organic solar cells:
      material selection and device architecture.
AB  - Thin-film blends or bilayers of donor- and acceptor-type organic semiconductors
      form the core of heterojunction organic photovoltaic cells. Researchers measure
      the quality of photovoltaic cells based on their power conversion efficiency, the
      ratio of the electrical power that can be generated versus the power of incident
      solar radiation. The efficiency of organic solar cells has increased steadily in
      the last decade, currently reaching up to 6%. Understanding and combating the
      various loss mechanisms that occur in processes from optical excitation to charge
      collection should lead to efficiencies on the order of 10% in the near future. In
      organic heterojunction solar cells, the generation of photocurrent is a cascade
      of four steps: generation of excitons (electrically neutral bound electron-hole
      pairs) by photon absorption, diffusion of excitons to the heterojunction,
      dissociation of the excitons into free charge carriers, and transport of these
      carriers to the contacts. In this Account, we review our recent contributions to
      the understanding of the mechanisms that govern these steps. Starting from
      archetype donor-acceptor systems of planar small-molecule heterojunctions and
      solution-processed bulk heterojunctions, we outline our search for alternative
      materials and device architectures. We show that non-planar phthalocynanines have
      appealing absorption characteristics but also have reduced charge carrier
      transport. As a result, the donor layer needs to be ultrathin, and all layers of
      the device have to be tuned to account for optical interference effects. Using
      these optimization techniques, we illustrate cells with 3.1% efficiency for the
      non-planar chloroboron subphthalocyanine donor. Molecules offering a better
      compromise between absorption and carrier mobility should allow for further
      improvements. We also propose a method for increasing the exciton diffusion
      length by converting singlet excitons into long-lived triplets. By doping a
      polymer with a phosphorescent molecule, we demonstrate an increase in the exciton
      diffusion length of a polymer from 4 to 9 nm. If researchers can identify
      suitable phosphorescent dopants, this method could be employed with other
      materials. The carrier transport from the junction to the contacts is markedly
      different for a bulk heterojunction cell than for planar junction cells. Unlike
      for bulk heterojunction cells, the open-circuit voltage of planar-junction cells
      is independent of the contact work functions, as a consequence of the balance of
      drift and diffusion currents in these systems. This understanding helps to guide
      the development of new materials (particularly donor materials) that can further
      boost the efficiency of single-junction cells to 10%. With multijunction
      architectures, we expect that efficiencies of 12-16% could be attained, at which
      point organic photovoltaic cells could become an important renewable energy
      source.

PMID- 19751056
TI  - State-to-state quantum reactive scattering calculations and rate constant for
      nitrogen atoms in collision with NO radicals at low temperatures.
AB  - Total and state-to-state probabilities have been determined for the N + NO -->
      N(2) + O reaction for collision energies up to 0.6 eV using a time-independent
      quantum mechanical method. The probabilities as a function of collision energy
      show broad oscillations, in strong contrast with previous theoretical results
      obtained by means of a time-dependent wave packet method that show a dense
      resonance structure. The rate constant has been calculated in the J-shifting
      approach for temperatures between 10 and 400 K. It is in good agreement with
      previous theoretical results obtained only at 100 K and above 200 K and
      experiments in a wide temperature range.

PMID- 19751058
TI  - Correlation between the atomic alignment and the alignment of XeX* (B, C)
      rotation in the reactions of oriented Xe ((3)P(2), M(J) = 2) + halogen (X)
      containing molecules.
AB  - The polarization of the XeX* (B) and XeX* (C) emissions in the reactions of
      oriented Xe* ((3)P(2), M(J) = 2) + halogen (X)-containing molecules (CCl(4),
      CF(3)Br, CF(3)I, CH(3)I, NF(3)) has been measured as a function of each magnetic
      M(J)' substate in the collision frame. The parallel polarization of the XeX* (B,
      C) emissions to the relative velocity vector is commonly observed for all
      magnetic M(J)' substates. The correlation between the atomic alignment (M(J)')
      and the M(J)'-dependent alignment (A(M(J)')) of the XeX* (B, C) rotation is found
      to be extremely different between the XeX* (B) and XeX* (C) channels: For XeX*
      (B), A(M(J)') is highest for the M(J)' = 0 state, except CCl(4), whereas the
      |M(J)'| = 2 states give the highest A(M(J)') for XeX* (C). Alternatively, the
      correlation between the configuration (L(Z)') of the inner 5p orbital and the
      L(Z)'-dependent alignment (A(L(Z)')) of the XeX* (B, C) rotations is revealed.
      The collision with |L(Z)'| = 1 causes a similar positive alignment A(L(Z)') for
      the XeX* (B) and XeX* (C) channels. The alignment A(L(Z)') at the collision with
      |L(Z)'| = 0 is extremely different between the XeX* (B) and XeX* (C) channels.
      The collision with L(Z)' = 0 induces no alignment of XeX* (C) except CF(3)I, that
      is, A(L(Z)'=0) approximately 0, whereas it induces the higher positive A(L(Z)')
      of XeX* (B). The different M(J)' dependence on the alignment of the XeX* (B, C)
      rotation between the XeX* (B) and XeX* (C) channels can be recognized as the
      change of reaction mechanism due to the difference in the favorable impact
      parameter for each M(J)' state between the XeX* (B) and XeX* (C) channels, which
      reflects the Omega' conservation in the course of ion-pair (Xe(+)-RX(-))
      formation.

PMID- 19751057
TI  - Aptamers generated from cell-SELEX for molecular medicine: a chemical biology
      approach.
AB  - Molecular medicine is an emerging field focused on understanding the molecular
      basis of diseases and translating this information into strategies for diagnosis
      and therapy. This approach could lead to personalized medical treatments.
      Currently, our ability to understand human diseases at the molecular level is
      limited by the lack of molecular tools to identify and characterize the distinct
      molecular features of the disease state, especially for diseases such as cancer.
      Among the new tools being developed by researchers including chemists, engineers,
      and other scientists is a new class of nucleic acid probes called aptamers, which
      are ssDNA/RNA molecules selected to target a wide range of molecules and even
      cells. In this Account, we will focus on the use of aptamers, generated from cell
      based selections, as a novel molecular tool for cancer research. Cancers
      originate from mutations of human genes. These genetic alterations result in
      molecular changes to diseased cells, which, in turn, lead to changes in cell
      morphology and physiology. For decades, clinicians have diagnosed cancers
      primarily based on the morphology of tumor cells or tissues. However, this method
      does not always give an accurate diagnosis and does not allow clinicians to
      effectively assess the complex molecular alterations that are predictive of
      cancer progression. As genomics and proteomics do not yet allow a full access to
      this molecular knowledge, aptamer probes represent one effective and practical
      avenue toward this goal. One special feature of aptamers is that we can isolate
      them by selection against cancer cells without prior knowledge of the number and
      arrangement of proteins on the cellular surface. These probes can identify
      molecular differences between normal and tumor cells and can discriminate among
      tumor cells of different classifications, at different disease stages, or from
      different patients. This Account summarizes our recent efforts to develop
      aptamers through cell-SELEX for the study of cancer and apply those aptamers in
      cancer diagnosis and therapy. We first discuss how we select aptamers against
      live cancer cells. We then describe uses of these aptamers. Aptamers can serve as
      agents for molecular profiling of specific cancer types. They can also be used to
      modify therapeutic reagents to develop targeted cancer therapies. Aptamers are
      also aiding the discovery of new cancer biomarkers through the recognition of
      membrane protein targets. Importantly, we demonstrate how molecular assemblies
      can integrate the properties of aptamers and, for example, nanoparticles or
      microfluidic devices, to improve cancer cell enrichment, detection and therapy.

PMID- 19751059
TI  - Interactions of dimethylsulfoxide with a dipalmitoylphosphatidylcholine monolayer
      studied by vibrational sum frequency generation.
AB  - The interactions between phospholipid monolayers and dimethylsulfoxide (DMSO)
      molecules were investigated by vibrational sum frequency generation (VSFG)
      spectroscopy in a Langmuir trough system. Both the head and the tail groups of
      dipalmitoylphosphatidylcholine (DPPC) as well as DMSO were probed to provide a
      comprehensive understanding of the interactions between DPPC and DMSO molecules.
      A condensing effect is observed for the DPPC monolayer on a concentrated DMSO
      subphase (>20 mol %). This effect results in a well-ordered conformation for the
      DPPC alkyl chains at very large mean molecular areas. Interactions between DMSO
      and DPPC headgroups were also studied. DMSO-induced dehydration of the DPPC
      phosphate group is revealed at DMSO concentration above 10 mol %. The average
      orientation of DMSO with DPPC versus dipalmitoylphosphate sodium salt (DPPA)
      monolayers was compared. The comparison revealed that DMSO molecules are
      perturbed and reorient because of the interfacial electric field created by the
      charged lipid headgroups. The orientation of the DPPC alkyl chains remains nearly
      unchanged in the liquid condensed phase with the addition of DMSO. This suggests
      that DMSO molecules are expelled from the condensed monolayer. In addition,
      implications for the DMSO-induced permeability enhancement of biological
      membranes from this work are discussed.

PMID- 19751060
TI  - Influence of fluorine atoms and aromatic rings on the acidity of ethanol.
AB  - Absolute gas-phase acidities Delta(acid)G(0)(OH) and Delta(acid)G(0)(CH) were
      calculated at the B3LYP and MP2 levels using six different standard basis sets
      for the OH and CH heterolytic bond cleavage of ethanol and twelve derivatives of
      the type CH(3-n)F(n)CHX(r)OH, where n ranges from zero to three and represents
      the number of fluorine atoms and r represents hydrogen and the type of aromatic
      ring, namely: X(0) = hydrogen, X(1) = phenyl, X(2) = 1-naphthyl, and X(3) = 9
      anthryl. The similarity between calculated and experimental Delta(acid)G(0)(OH)
      values for ethanol (1a), 2-fluoroethanol (1b), 2,2-difluoroethanol (1c), 2,2,2
      trifluoroethanol (1d), and 1-phenylethanol (2a) was used to validate the right
      theoretical method for this study. Substituent partial contributions to hydroxyl
      , methylene-, and methine-hydrogen acidities were evaluated by linear
      combination. Good parameter fittings of the primary and secondary alcohols were
      obtained and interpreted as additive contribution of the substituent effects. The
      nonlinear contributions were identified. Calculations prove that fluoroalcohols
      exhibit C-H acidity, which is usually lower than O-H acidity. In principle, the
      inversion of this acidity order is possible by the introduction of a large
      aromatic ring instead to increase the number of fluorine atoms.

PMID- 19751061
TI  - Toward understanding metal-binding specificity of porphyrin: a conceptual density
      functional theory study.
AB  - Porphyrin is a key cofactor of hemoproteins. The complexes it forms with divalent
      metal cations such as Fe, Mg, and Mn compose an important category of compounds
      in biological systems, serving as a reaction center for a number of essential
      life processes. Employing density functional theory (DFT) and conceptual DFT
      approaches, the structural properties and reactivity of (pyridine)(n)-M-porphyrin
      complexes were systematically studied for the following selection of divalent
      metal cations: Mg, Ca, Cr, Mn, Co, Ni, Cu, Zn, Ru, and Cd with n varying from 0,
      1, to 2. Metal selectivity and porphyrin specificity were investigated from the
      perspective of both structural and reactivity properties. Quantitative structural
      and reactivity relationships have been discovered between bonding interactions,
      charge distributions, and DFT chemical reactivity descriptors. These results are
      beneficial to our understanding of the chemical reactivity and metal cation
      specificity for heme-containing enzymes and other metalloproteins alike.

PMID- 19751062
TI  - Solvent dependence of n-pi* absorption in acetone.
AB  - A barely resolved structure can cause considerable loss of precision when
      locating the maxima of broad spectra. The centers of band envelopes were
      determined for the acetone n-pi* absorption in vapor, pure liquid, and solutions
      at 293 K. A complementary method of "band-halving" is proposed for accurate
      measurement of solvent-induced displacements. Solvent shifts span from -280 cm(
      1) in CCl(4) to 465 cm(-1) in acetonitrile, and further to 1785 cm(-1) in
      hydrogen-bonding water, being negligible in n-alkanes. In the latter case the
      dispersive and induction shift components almost cancel mutually. Unbiased values
      of absolute frequency shifts will provide a reference to quantum chemical
      calculations, in particular, in nonpolar and weakly polar solvents where much
      controversy exists. The dipole moment in the excited state (mu(e) = 1.81 +/- 0.2
      D, Deltamu = -1.81 D) and polarizability change (Deltaalpha = 0.6 +/- 0.2 A(3))
      were estimated. A solvent set where the Onsager model is apparently applicable
      was used for the determination of mu(e). Remarkably, the bandwidth at half
      maximum (fwhm) decreases in liquids, including water (6270 cm(-1)), as compared
      to vapor (6680 cm(-1)).

PMID- 19751063
TI  - Single-domain antibody-nanoparticles: promising architectures for increased
      staphylococcus aureus detection specificity and sensitivity.
AB  - Because antibodies are highly target-specific and nanoparticles possess diverse,
      material-dependent properties that can be exploited in order to label and
      potentially identify biomolecules, the development of antibody-nanoparticle
      conjugates (nanoconjugates) has huge potential in biodiagnostics. Here, we
      describe a novel superparamagnetic nanoconjugate, one whose recognition component
      is a single-domain antibody. It is highly active toward its target Staphylococcus
      aureus, displays long shelf life, lacks cross-reactivity inherent to traditional
      homologue whole antibodies, and captures a few dozen S. aureus cells in a mixed
      cell population with ~100% efficiency and specificity. We ascribe the excellent
      performance of our nanoconjugate to its single-domain antibody component and
      recommend it as a general purpose recognition element.

PMID- 19751064
TI  - Single-molecule bonds characterized by solid-state nanopore force spectroscopy.
AB  - Weak molecular interactions drive processes at the core of living systems, such
      as enzyme-substrate interactions, receptor-ligand binding, and nucleic acid
      replication. Single-molecule force spectroscopy is a remarkable tool for
      revealing molecular scale energy landscapes of noncovalent bonds, by exerting a
      mechanical force directly on an individual molecular complex and tracking its
      survival as a function of time and applied force. In principle, force
      spectroscopy methods can also be used for highly specific molecular recognition
      assays, by directly characterizing the strength of bonds between probe and target
      molecules. However, complexity and low throughput of conventional force
      spectroscopy techniques render such biosensing applications impractical. Here we
      demonstrate a straightforward single-molecule approach, suitable for both
      biophysical studies and molecular recognition assays, in which a approximately 3
      nm silicon nitride nanopore is used to determine the bond lifetime spectrum of
      the biotin-neutravidin complex. Thousands of individual molecular complexes are
      captured and dissociated in the solid-state nanopore under constant applied
      forces, ranging from 400 to 900 mV, allowing us to extract the location of the
      energy barrier that governs the interaction, mapped at Deltax approximately 0.5
      nm. These results highlight the capacity of a solid-state nanopore to detect and
      characterize intermolecular interactions and demonstrate how this could be
      applied to rapid, highly specific molecular detection assays.

PMID- 19751065
TI  - Atomic force microscope nanomanipulation with simultaneous visual guidance.
AB  - Atomic force microscopy (AFM) has been used to assemble prototype nanostructures
      consisting of colloidal nanoparticles. In the standard manipulation protocol, the
      AFM is used either as a manipulation tool or an imaging tool, but not both at the
      same time. We developed a new nanomanipulation protocol in which simultaneous
      visual guidance is obtained during manipulation. As an example, Au nanoparticles
      were manipulated on a substrate in two steps. First, a nanoparticle is kicked
      with the z feedback off. This kicking event reduces the static friction. Second,
      the nanoparticle is dribbled to a target position in tapping mode, and visual
      guidance is provided by a ghost trace of the nanoparticle. The new manipulation
      protocol greatly improves efficiency of manipulating small nanoparticles (15 nm
      in diameter or smaller). Our work highlights the importance and challenges of
      understanding friction at the nanoscale.

PMID- 19751066
TI  - Ge(1-x) Mn(x) clusters: central structural and magnetic building blocks of
      nanoscale wire-like self-assembly in a magnetic semiconductor.
AB  - Controlled nanoscale self-assembly of magnetic entities in semiconductors opens
      novel perspectives for the tailoring of magnetic semiconductor films and
      nanostructures with room temperature functionality. We report that a strongly
      directional self-assembly in growth direction in Mn-alloyed Ge is due to a
      stacking of individual Ge(1-x)Mn(x) clusters. The clusters represent the relevant
      entities for the magnetization of the material. They are formed of a core-shell
      structure displaying a Mn concentration gradient. While the magnetic moments seem
      to be carried by the shells of the clusters, their core is magnetically inactive.

PMID- 19751067
TI  - Length dependence of conductance in aromatic single-molecule junctions.
AB  - Using a scattering-state approach incorporating self-energy corrections to the
      junction level alignment, the conductance G of oligophenyldiamine-Au junctions is
      calculated and elucidated. In agreement with experiment, we find G decays
      exponentially with the number of phenyls with decay constant beta = 1.7. A
      straightforward, parameter-free self-energy correction, including electronic
      exchange and correlations beyond density functional theory (DFT), is found to be
      essential for understanding the measured values of both G and beta. Importantly,
      our results confirm quantitatively the picture of off-resonant tunneling in these
      systems and show that exchange and correlation effects absent from standard DFT
      calculations contribute significantly to beta.

PMID- 19751068
TI  - Nanoscale imaging of exciton transport in organic photovoltaic semiconductors by
      tip-enhanced tunneling luminescence.
AB  - In organic solar cells, the efficiency of the exciton transport and dissociation
      across donor-acceptor (D/A) interfaces is controlled by the nanoscale
      distribution of the donor and acceptor phases. The observation of
      photoluminescence quenching is often used as confirmation for efficient exciton
      dissociation but provides no information on the nanoscopic nature of the exciton
      transport. Here we demonstrate nanoscale imaging of the exciton transport in
      films consisting of the conjugated polymer poly(3-hexylthiophene) (P3HT, electron
      donor) blended with the C60 derivative 1-(3-methoxycarbonyl)-propyl-1-phenyl
      (6,6)C61 (PCBM, electron acceptor) by a tunneling luminescence spectroscopy based
      on atomic force microscopy. The excitonic luminescence is significantly enhanced
      when the conjugated polymer is coupled to the plasmon excitation at the tip (tip
      enhanced luminescence). This effect allows one to dramatically improve the
      detection efficiency of the excitonic luminescence and, consequently, resolve
      individual domains of the conjugated polymer in which the exciton will recombine
      before dissociation at the D/A interface. Under thermal annealing conditions
      promoting the segregation of the donor and acceptor phases, a clear increase of
      the luminescence is seen from polymer-rich regions, consistent with domains of
      dimensions much larger than the exciton diffusion length. The described scanning
      luminescence microscopy can thus be applied to the optimization of the blends
      used in solar cells.

PMID- 19751069
TI  - Very large scale integration of nanopatterned YBa2Cu3O7-delta Josephson junctions
      in a two-dimensional array.
AB  - Very large scale integration of Josephson junctions in a two-dimensional series
      parallel array has been achieved by ion irradiating a YBa(2)Cu(3)O(7-delta) film
      through slits in a nanofabricated mask created with electron beam lithography and
      reactive ion etching. The mask consisted of 15820 high aspect ratio (20:1), 35 nm
      wide slits that restricted the irradiation in the film below to form Josephson
      junctions. Characterizing each parallel segment k, containing 28 junctions, with
      a single critical current I(ck) we found a standard deviation in I(ck) of about
      16%.

PMID- 19751070
TI  - Sonification design for complex work domains: dimensions and distractors.
AB  - Sonification--representing data in sound--is a potential method for supporting
      human operators who have to monitor dynamic processes. Previous research has
      investigated a limited number of sound dimensions and has not systematically
      investigated the impact of dimensional interactions on sonification
      effectiveness. In three experiments the authors investigated accuracy for
      identifying changes in six target auditory dimensions of a continuous pulse
      stream under three conditions: no distractor, one distractor, and five
      distractors. In Experiment 1 amplitude, frequency, harmonics, speed, tremolo
      (cycles per pulse), and width were tested. Accuracy and patterns of interaction
      between the dimensions were mapped. In Experiment 2 the same dimensions were
      tested but tremolo was operationalized as cycles per second (Hz). The patterns of
      interaction between the temporal dimensions differed from Experiment 1. In
      Experiment 3 the amplitude contour of the pulse stream was changed. The
      dimensions tested were amplitude, frequency, formants, speed, tremolo (cycles per
      period), and width. Results showed low accuracy for formants and many
      interactions, both positive and negative between the dimensions. The authors
      interpret the results in terms of theories of perceptual interference in auditory
      dimensions.

PMID- 19751071
TI  - Evaluating science arguments: evidence, uncertainty, and argument strength.
AB  - Public debates about socioscientific issues are increasingly prevalent, but the
      public response to messages about, for example, climate change, does not always
      seem to match the seriousness of the problem identified by scientists. Is there
      anything unique about appeals based on scientific evidence-do people evaluate
      science and nonscience arguments differently? In an attempt to apply a systematic
      framework to people's evaluation of science arguments, the authors draw on the
      Bayesian approach to informal argumentation. The Bayesian approach permits
      questions about how people evaluate science arguments to be posed and comparisons
      to be made between the evaluation of science and nonscience arguments. In an
      experiment involving three separate argument evaluation tasks, the authors
      investigated whether people's evaluations of science and nonscience arguments
      differed in any meaningful way. Although some differences were observed in the
      relative strength of science and nonscience arguments, the evaluation of science
      arguments was determined by the same factors as nonscience arguments. Our results
      suggest that science communicators wishing to construct a successful appeal can
      make use of the Bayesian framework to distinguish strong and weak arguments.

PMID- 19751072
TI  - Bringing meaning to numbers: the impact of evaluative categories on decisions.
AB  - Decision makers are often quite poor at using numeric information in decisions.
      The results of 4 experiments demonstrate that a manipulation of evaluative
      meaning (i.e., the extent to which an attribute can be mapped onto a good/bad
      scale; this manipulation is accomplished through the addition of visual boundary
      lines and evaluative labels to a graphical format) has a robust influence in
      health judgments and choices and across diverse adult populations. The
      manipulation resulted in greater use of numeric quality-of-care information in
      judgments and less reliance on an irrelevant affective state among the less
      numerate. Recall results for provided quality-of-care numbers suggested that the
      manipulation did not influence depth of number processing with the exception of
      cost information that was not remembered as well. Results of a reaction-time
      paradigm revealed that feelings were more accessible than thoughts in the
      presence of the manipulation, suggesting that the effect may be due, at least in
      part, to an affective mechanism. Numeric information is often provided in
      decisions, but may not be usable by consumers without assistance from information
      providers. Implications for consumer decision making and the functions of affect
      are discussed.

PMID- 19751073
TI  - Text skimming: the process and effectiveness of foraging through text under time
      pressure.
AB  - Is Skim reading effective? How do readers allocate their attention selectively?
      The authors report 3 experiments that use expository texts and allow readers only
      enough time to read half of each document. Experiment 1 found that, relative to
      reading half the text, skimming improved memory for important ideas from a text
      but did not improve memory of less important details or of inferences made from
      information within the text. Experiment 2 found no advantage of skimming over
      reading the first or second half of every paragraph. Two final experiments using
      a hierarchical, Website-like layout of documents showed that the advantage of
      skimming found in Experiment 1 was dependent on the linkages between pages and,
      thus, the ease with which participants could navigate through the text. Data on
      page-by-page reading times and eye-tracking analyses from Experiment 2 indicated
      that Skim readers spent more time reading text that was earlier in the paragraph,
      toward the top of the page and in an earlier page of the document. These findings
      were interpreted as evidence in support of a "satisficing" account of skimming
      process.

PMID- 19751074
TI  - The pretesting effect: do unsuccessful retrieval attempts enhance learning?
AB  - Testing previously studied information enhances long-term memory, particularly
      when the information is successfully retrieved from memory. The authors examined
      the effect of unsuccessful retrieval attempts on learning. Participants in 5
      experiments read an essay about vision. In the test condition, they were asked
      about embedded concepts before reading the passage; in the extended study
      condition, they were given a longer time to read the passage. To distinguish the
      effects of testing from attention direction, the authors emphasized the tested
      concepts in both conditions, using italics or bolded keywords or, in Experiment
      5, by presenting the questions but not asking participants to answer them before
      reading the passage. Posttest performance was better in the test condition than
      in the extended study condition in all experiments--a pretesting effect--even
      though only items that were not successfully retrieved on the pretest were
      analyzed. The testing effect appears to be attributable, in part, to the role
      unsuccessful tests play in enhancing future learning.

PMID- 19751075
TI  - Coping with fear through suppression and avoidance of threatening information.
AB  - Fear appeal communications are widely used by social marketers in their efforts
      to persuade individuals to refrain from engaging in risky behaviors. The present
      research shows that exposure to a fear appeal can lead to the suppression of
      concepts semantically related to the threat and bias attentional resources away
      from threat-relevant information. Participants in the experimental condition
      viewed a fear appeal advertisement depicting the negative consequences of
      drinking and driving. The results of a reaction time task showed inhibited
      responses to words semantically related to drinking (e.g., beer, party) relative
      to a baseline group that controlled for priming effects (Experiment 1a) and level
      of fear (Experiment 1b). Furthermore, those in the experimental condition were
      shown to adopt an attention avoidance processing style, decreasing attention to
      alcohol-related advertisements appearing in a mock magazine (Experiments 2a and
      2b). Because processing of alcohol-related advertising has been linked previously
      to an increase in drinking and driving, inhibited processing of such
      advertisements suggests a positive outcome of suppression effects. This contrasts
      with prior claims suggesting that suppression is counter to prevention-based
      efforts.

PMID- 19751076
TI  - How many cigarettes did you smoke? Assessing cigarette consumption by global
      report, Time-Line Follow-Back, and ecological momentary assessment.
AB  - OBJECTIVE: This study evaluated and compared several methods of assessing daily
      cigarette consumption. DESIGN: Comparison of measures of daily cigarette
      consumption from several sources, from 232 smokers entering a smoking cessation
      program. MAIN OUTCOME MEASURES: Global reports of average smoking, Time-Line
      Follow-Back (TLFB) recall for the week preceding the study (premonitoring TLFB),
      2 weeks' cigarette recordings using electronic diaries and ecological momentary
      assessment (EMA), and TLFB recall of smoking during EMA (monitored TLFB).
      RESULTS: Global reports and premonitoring TLFB showed severe digit bias: six
      times as many values as expected were rounded at 10. Monitored TLFB also showed
      substantial digit bias (four times). EMA data showed none. EMA averaged 2.6
      cigarettes lower than monitored TLFB, but exceeded TLFB on 32% of days. Across
      days, EMA and TLFB only correlated 0.29. Daily variations in TLFB did not
      correlate with variations in carbon monoxide (CO) measures taken on 3 days, but
      EMA measures did; among participants whose CO varied, r = .69. CO correlated with
      EMA cigarettes recorded in the preceding 2 hours, suggesting timely recording of
      cigarettes. CONCLUSION: TLFB measures are limited for precise assessment of
      cigarette consumption. EMA measures appear to be useful for tracking smoking, and
      likely other health-relevant events.

PMID- 19751077
TI  - Electronic recording, self-report, and bias in measuring cigarette consumption.

PMID- 19751078
TI  - The role of time perspective in smoking cessation amongst older English adults.
AB  - OBJECTIVE: To study the longitudinal relationship between time perspective and
      smoking cessation over 4 years of follow-up among a cohort of older English
      adults and to determine whether the predictive utility of time perspective in
      smoking cessation. DESIGN: Analysis of data from core members of the English
      Longitudinal Survey of Ageing who took part in face-to-face interviews in 2002,
      2004, and 2006 (n = 7,174). MAIN OUTCOME MEASURES: Time perspective was measured
      using a question on time period for financial planning. Smoking at baseline and
      quitting over follow-up was determined through self-report. RESULTS: At baseline,
      planning for longer periods was associated with lower odds of being a smoker,
      after controlling for age, gender, and education. Among those who were smokers at
      baseline, planning for longer periods at baseline was associated with increased
      odds of quitting over 4 years, after controlling for age, gender, and education.
      CONCLUSION: Including help to become more future orientated in smoking cessation
      interventions may increase their effectiveness.

PMID- 19751079
TI  - The effects of smoking self-identity and quitting self-identity on attempts to
      quit smoking.
AB  - OBJECTIVE: To examine the effect of two types of self-identity on attempts to
      quit smoking: self-identity in terms of smoking and self-identity in terms of
      quitting. DESIGN: A prospective survey among an initial sample of 3,411 smokers.
      Smoking history variables and psychosocial variables from the theory of planned
      behavior are also measured. MAIN OUTCOME MEASURES: Intention to quit smoking and
      smoking cessation attempts 4 months later. RESULTS: Both smoking identity and
      quitting identity matter, but they appear to play different roles in explaining
      intention to quit and in predicting actual attempts to quit. Quitting identity is
      particularly important for intention to quit, whereas both quitting identity and
      smoking identity are important for actually trying to quit. Recent attempts to
      quit slightly attenuate the negative effect of smoking identity on attempts to
      quit. CONCLUSION: A broader interpretation of self-identity in terms of both
      current and aspired behavior offers a better understanding of when people might
      change health-relevant behavior.

PMID- 19751080
TI  - Effectiveness of experimenter-provided and self-generated implementation
      intentions to reduce alcohol consumption in a sample of the general population: a
      randomized exploratory trial.
AB  - OBJECTIVE: To test the effectiveness of implementation intentions to decrease
      alcohol consumption and control for possible demand characteristics by employing
      an active control condition and contrasting experimenter-provided with self
      generated implementation intentions. DESIGN: Two hundred forty-eight participants
      were randomly allocated to 1 of 4 conditions: questionnaire-only; questionnaire
      plus planning instruction; questionnaire, planning instruction plus experimenter
      provided implementation intention; or questionnaire, planning instruction plus
      self-generated implementation intention. MAIN OUTCOME MEASURE: Alcohol intake.
      RESULTS: There were clinically and statistically significant decreases in alcohol
      consumption in the 2 experimental conditions, but not in the 2 control
      conditions, F(3, 237) = 3.34, p < .05, etap(2) = .04. There were no significant
      differences between experimenter-provided and self-generated implementation
      intentions (p = .62). Compliance moderated the effects of self-generated
      implementation intentions only, such that alcohol intake only significantly
      decreased in participants who complied with the instructions, F(1, 52) = 4.20, p
      < .05, etap(2) = .07. However, simply choosing an experimenter-provided
      implementation intention was just as effective as writing it out in full,
      implying that implementation intentions work even with minimal information
      processing. CONCLUSION: The findings further support use of implementation
      intentions to protect against health risk behaviors and are congruent with
      laboratory research showing that implementation intentions are a case of
      strategic automaticity.

PMID- 19751081
TI  - Psychological vulnerability and stress: the effects of self-affirmation on
      sympathetic nervous system responses to naturalistic stressors.
AB  - OBJECTIVE: Everyday stressors can threaten valued aspects of the self. Self
      affirmation theory posits that this threat could be attenuated if individuals
      affirm alternative self-resources. The present study examined whether self
      affirmation would buffer cumulative stress responses to an ongoing academic
      stressor. DESIGN: Undergraduate participants provided 15-hr urine samples on the
      morning of their most stressful examination and baseline samples 14 days prior to
      the examination. Participants were randomly assigned to the self-affirmation
      condition where they wrote two essays on important values over the 2-week period
      prior to exam, or a control condition. MAIN OUTCOME MEASURES: Samples were
      analyzed for urinary catecholamine excretion (epinephrine, norepinephrine), an
      indicator of sympathetic nervous system activation. Participants also indicated
      their appraisals of the examination experience. RESULTS: Participants in the
      control condition increased in cumulative epinephrine levels from baseline to
      examination, whereas participants in the self-affirmation condition did not
      differ from baseline to examination. The buffering effect of self-affirmation was
      strongest among individuals most concerned about negative college evaluation,
      those most psychologically vulnerable. CONCLUSION: The findings demonstrate that
      sympathetic nervous system responses to naturalistic stressors can be attenuated
      by self-affirmation. Discussion centers on psychological pathways by which
      affirmation can reduce stress and the implications of the findings for health
      outcomes among chronically stressed participants.

PMID- 19751082
TI  - How self-affirmation reduces defensive processing of threatening health
      information: evidence at the implicit level.
AB  - OBJECTIVE: Self-affirmation reduces defensive responses to threatening health
      information, but little is known about the cognitive processes instigated by self
      affirmation. This study tested whether self-affirmation increases responsiveness
      to threatening health information at the implicit level. DESIGN: In an
      experimental study (N = 84), the authors presented high- (coffee drinkers) and
      low-relevance (noncoffee drinkers) participants with threatening health
      information linking caffeine consumption to health problems. Prior to reading
      this information, the authors manipulated self-affirmation. MAIN OUTCOME
      MEASURES: Participants completed an unobtrusive lexical decision task to measure
      the accessibility of threat-related cognitions and reported their perceptions of
      message quality and intentions to take precautions. RESULTS: Among high-relevance
      participants, self-affirmation increased the accessibility of threat-related
      cognitions, increased perceptions of message quality, and promoted adaptive
      behavioral intentions. CONCLUSION: The findings suggest that self-affirmation can
      increase implicit responsiveness to threatening health information among a target
      audience, that is, people for whom the health information is highly relevant.

PMID- 19751083
TI  - Cognitive and emotional factors predicting decisional conflict among high-risk
      breast cancer survivors who receive uninformative BRCA1/2 results.
AB  - OBJECTIVE: To investigate high-risk breast cancer survivors' risk reduction
      decision making and decisional conflict after an uninformative BRCA1/2 test.
      DESIGN: Prospective, longitudinal study of 182 probands undergoing BRCA1/2
      testing, with assessments 1-, 6-, and 12-months postdisclosure. MEASURES: Primary
      predictors were health beliefs and emotional responses to testing assessed 1
      month postdisclosure. Main outcomes included women's perception of whether they
      had made a final risk management decision (decision status) and decisional
      conflict related to this issue. RESULTS: There were four patterns of decision
      making, depending on how long it took women to make a final decision and the
      stability of their decision status across assessments. Late decision makers and
      nondecision makers reported the highest decisional conflict; however, substantial
      numbers of women--even early and intermediate decision makers--reported elevated
      decisional conflict. Analyses predicting decisional conflict 1- and 12-months
      postdisclosure found that, after accounting for control variables and decision
      status, health beliefs and emotional factors predicted decisional conflict at
      different timepoints, with health beliefs more important 1 month after test
      disclosure and emotional factors more important 1 year later. CONCLUSION: Many of
      these women may benefit from decision making assistance.

PMID- 19751084
TI  - Effects of supportive-expressive group therapy on pain in women with metastatic
      breast cancer.
AB  - OBJECTIVE: To examine whether a group intervention including hypnosis can reduce
      cancer pain and trait hypnotizability would moderate these effects. DESIGN: This
      randomized clinical trial examined the effects of group therapy with hypnosis
      (supportive-expressive group therapy) plus education compared to an education
      only control condition on pain over 12 months among 124 women with metastatic
      breast cancer. MAIN OUTCOME MEASURES: Pain and suffering, frequency of pain, and
      degree of constant pain were assessed at baseline and 4-month intervals. Those in
      the treatment group also reported on their experiences using the hypnosis
      exercises. RESULTS: Intention-to-treat analyses indicated that the intervention
      resulted in significantly less increase in the intensity of pain and suffering
      over time, compared to the education-only group, but had no significant effects
      on the frequency of pain episodes or amount of constant pain, and there was no
      interaction of the intervention with hypnotizability. Within the intervention
      group, highly hypnotizable participants, compared to those less hypnotizable,
      reported greater benefits from hypnosis, employed self-hypnosis more often
      outside of group, and used it to manage other symptoms in addition to pain.
      CONCLUSION: These results augment the growing literature supporting the use of
      hypnosis as an adjunctive treatment for medical patients experiencing pain.

PMID- 19751085
TI  - A randomized trial of a representational intervention for cancer pain: does
      targeting the dyad make a difference?
AB  - OBJECTIVE: To determine the efficacy in overcoming attitudinal barriers to
      reporting cancer pain and using analgesics of an educational intervention
      presented to patients accompanied by a significant other (SO) as compared with
      patients alone. DESIGN: Patient-SO pairs (N = 161) were randomized to the dyad
      condition (patient and SO received the intervention), solo condition (patient
      received the intervention), or care as usual. Dyad and solo conditions received
      the intervention at baseline (T1) and 2 and 4 weeks later. MAIN OUTCOME MEASURES:
      Patients' and SOs' attitudes about analgesic use and patients' pain outcomes
      (pain severity, pain relief, interference with life, negative mood, and global
      quality of life [QOL]) at T1, 5 weeks later (T2), and 9 weeks later (T3).
      RESULTS: Completers' analyses revealed no significant differences between groups
      at T2. At T3, patients in the dyad and the solo groups showed greater decreases
      in attitudinal barriers as compared with controls. T1-T3 changes in patients'
      barriers mediated between the dyad and solo interventions and pain severity, pain
      relief, pain interference, negative mood, and global QOL. CONCLUSION: The
      intervention was no more efficacious when it was presented to dyads than to
      patients alone. Conditions under which SOs should be included in interventions
      need to be determined.

PMID- 19751086
TI  - The role of sexuality in cervical cancer screening among Chinese women.
AB  - OBJECTIVE: Chinese women have significantly lower rates of Papanicolaou (Pap)
      testing than Euro-Canadian women despite efforts to promote testing. Evidence
      suggests that Chinese women's reluctance to undergo Pap testing may be related to
      culture-linked discomfort with sexuality. The purpose of this study was to
      explore the role of sexuality in the interaction between acculturation and Pap
      testing. DESIGN: Euro-Canadian (n = 213) and Chinese (n = 260) female university
      students completed a battery of questionnaires. MAIN OUTCOME MEASURES:
      Questionnaires assessing sexual knowledge, sexual function, acculturation, and
      Pap testing frequency. RESULTS: Euro-Canadian women had significantly more
      accurate sexual knowledge, higher levels of sexual functioning, a broader
      repertoire of sexual activities, and higher Pap testing rates. Chinese women were
      more likely to cite embarrassment as a barrier to Pap testing. Heritage
      acculturation, but not mainstream acculturation, predicted Chinese women's Pap
      testing behavior. Mainstream acculturation was associated with more accurate
      sexual knowledge and greater sexual desire and satisfaction. CONCLUSION: The
      findings provide support for the hypothesis that low Pap testing rates in Chinese
      women may be associated with heritage acculturation, although the hypothesis that
      sexual function would predict Pap testing behavior was not supported.

PMID- 19751087
TI  - The association of parent behaviors, chronic pain, and psychological problems
      with venipuncture distress in infants: the Generation R study.
AB  - OBJECTIVE: To examine the association of parent behavior with infant distress
      during a potentially painful medical procedure. A second aim was to investigate
      the association of parent chronic pain and psychological problems with parent
      behavior and infant distress during the procedure. DESIGN: Population-based
      cohort study with both cross-sectional and prospective measurements. MAIN OUTCOME
      MEASURES: Video recordings of 275 parents and their 14-month-old infant
      undergoing venipuncture were coded with an observational instrument to yield
      measures of infant distress behaviors and parent behaviors, such as reassuring,
      showing empathy, praising, and distracting. Parent chronic pain and psychological
      problems were assessed through questionnaires. RESULTS: Infants cried 58% of
      procedure duration. Parent reassuring occurred 34% of procedure duration, and
      parent distracting occurred 37% of procedure duration. Infant distress was
      positively related to parent reassuring and negatively related to parent
      praising. Parent chronic pain was related to increased parent distracting but not
      to parent reassuring. Parent psychological problems were not associated with
      parent behavior and infant distress. CONCLUSION: Parent behavior rather than
      psychological traits is related to increased venipuncture distress in young
      infants. This finding suggests that the focus should be on interventions based on
      behavior modification.

PMID- 19751088
TI  - Blood lead (Pb) levels: further evidence for an environmental mechanism
      explaining the association between socioeconomic status and psychophysiological
      dysregulation in children.
AB  - OBJECTIVE: The authors recently reported that blood lead (Pb) was a significant
      mediator for the positive association between socioeconomic status (SES) and
      peripheral vascular responses to acute stress in children (B. B. Gump et al.,
      2007). The present study considers the possibility that Pb may also mediate an
      association between SES and cortisol responses to acute stress. DESIGN: Early
      childhood Pb exposure was tested as a mediator for cross-sectional associations
      between SES and cortisol responses. MAIN OUTCOME MEASURES: The primary outcome
      was cortisol responses to acute stress in 9.5-year-old children (N = 108).
      RESULTS: Lower family income was associated with significantly greater cortisol
      levels following an acute stress task. A mediational analysis confirmed that Pb
      was a significant mediator for this association. CONCLUSION: These results
      reaffirm the importance of considering the chemical environment as well as social
      and psychological environment when evaluating psychophysiological effects of low
      SES.

PMID- 19751089
TI  - Cognitive word use during marital conflict and increases in proinflammatory
      cytokines.
AB  - OBJECTIVE: To examine whether greater cognitive engagement during a marital
      conflict discussion, as evidenced by use of words that suggest thinking and
      meaning-making, results in attenuated proinflammatory cytokine increases to
      stress and wounding. DESIGN: Husbands and wives (N = 84 individuals) were
      observed during two separate 24-hr visits: each visit included a wounding
      procedure, which was followed by a nonconflictive marital discussion (first
      visit) and a conflictive marital discussion (second visit). MAIN OUTCOME
      MEASURES: Serum proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis
      factor-alpha (TNF-alpha). RESULTS: Individuals who used more cognitive processing
      words during the conflict discussion (but not the nonconflictive discussion)
      showed smaller increases in serum IL-6 and TNF-alpha over 24 hours; they also had
      lower levels of both cytokines 24 hours after baseline controlling for
      demographics, hostility, depressed mood, positive and negative interactions, and
      marital quality. Effects of word use were not mediated by ruminative thoughts
      after conflict. Although both men and women benefited from their own cognitive
      engagement, only husbands' IL-6 patterns were affected by spouses' engagement.
      CONCLUSION: In accord with research demonstrating the value of cognitive
      processing in emotional disclosure, this research suggests that productive
      communication patterns may help mitigate the adverse effects of relationship
      conflict on inflammatory dysregulation.

PMID- 19751090
TI  - Material and social incentives to participation in behavioral interventions: a
      meta-analysis of gender disparities in enrollment and retention in experimental
      human immunodeficiency virus prevention interventions.
AB  - OBJECTIVE: A meta-analysis was conducted to test theoretical hypotheses about the
      predictors of enrollment and completion of condom-use-promotion interventions
      among men and women. DESIGN: A meta-analysis summarized research reports of the
      efficacy of experimental interventions on human immunodeficiency virus (HIV)
      prevention. MAIN OUTCOME MEASURES: The outcome measure consisted of (a) a measure
      of participation, obtained by subtracting the actual number of participants from
      the number of the invited people, and (b) a measure of retention was obtained by
      subtracting the number of participants who completed the intervention from the
      number of commencers. RESULTS: Experimental interventions providing instrumental
      and financial resources (e.g., payments) increased initiation and retention more
      among predominantly male samples, whereas experimental interventions using group
      formats increased initiation and retention more among predominantly female
      samples. These patterns remained while controlling for past condom use, other HIV
      risk behaviors, and demographics associated with gender composition. CONCLUSION:
      People seek out HIV-prevention interventions to fulfill gender-specific needs,
      and these differences must be taken into account in the design of HIV-prevention
      interventions.

PMID- 19751091
TI  - Blood pressure reactivity and cognitive function in the Baltimore Longitudinal
      Study of Aging.
AB  - OBJECTIVE: Several blood pressure indexes of autonomic dysregulation, including
      stress-induced blood pressure responses (i.e., reactivity), have been associated
      previously with stroke, silent cerebrovascular disease, and decreased cognitive
      function. DESIGN: The authors examined the cross-sectional relations among
      systolic blood pressure (SBP) and diastolic blood pressure (DBP) reactivity and
      cognitive function in a sample of stroke- and dementia-free older adults (n = 73,
      53% male, 72% Caucasian, mean age = 70.14 years) from the Baltimore Longitudinal
      Study of Aging. MAIN OUTCOME MEASURES: Age, education, baseline, and reactive
      blood pressure levels were regressed on cognitive test scores measuring the
      domains of attention, learning and memory, verbal functions/language skills, and
      perceptuo-motor speed. A Bonferroni correction was employed and results
      significant at the standard p < .05 level are discussed as marginally
      significant. RESULTS: After adjustment for age, education, and resting blood
      pressure, greater SBP reactivity was associated with poorer performance on Digits
      Forward (R2 = .110, p = .007) and greater DBP reactivity was associated with
      poorer performance on Digits Forward (R(2) = .124, p = .003) and the Boston
      Naming Test (R(2) = .118, p = .008); associations with DBP reactivity and Alpha
      Span (R(2) = .104; p = .019) and CVLT free recall short delay (R(2) = .066, p =
      .032) were marginally significant. CONCLUSIONS: Greater BP reactivity was
      associated with poorer performance on tests of attention, verbal memory, and
      confrontation naming. BP reactivity may be a biobehavioral risk factor for
      lowered levels of cognitive performance.

PMID- 19751093
TI  - (Mis-) Direction of effect sizes.

PMID- 19751094
TI  - An investigation of medication information transfer and application in aged care
      facilities in an Australian rural setting.
AB  - INTRODUCTION: As patients move within Australia's increasingly complex healthcare
      system, it is desirable that they receive uninterrupted, timely and accurate
      administration of medication. For this to occur, effective communication of
      medication information is required, and mechanisms must be in place to ensure
      timely administration. This study focused on these issues as they apply to
      patients being admitted to aged care facilities in an Australian rural setting,
      including investigation of the transfer and early application of information
      about their current medications (or 'medication information'). Electronic
      prescribing and associated information transfer may improve the transfer of
      medication information in the future; however, this study focused on the current
      situation in rural Australia. METHOD: In this observational study, patient
      outcomes and participating nurses' experience of medication issues related to
      admissions to rural residential aged care facilities from an acute hospital, a
      rehabilitation facility, another aged care facility or the community were
      investigated. Data were collected using a customised questionnaire completed by
      nursing staff at participating aged care facilities. RESULTS: Data relating to 59
      individual patient transfers were obtained from 14 aged care facilities. A number
      of pathways for the communication of medication information were identified, with
      timely and effective information transfer occurring for most patients. However,
      one in five patients experienced a delay of up to 4 hours, and a limited number
      of incidents of inadequate information transfer were identified. While most
      patient transfers occurred with 12 or more hours notice, one in ten transfers
      occurred with no more than one hour of notice. Transfers were not evenly
      distributed among week days; however, very few transfers occurred after 5 pm on
      Friday. A number of staff reported that they had felt it necessary to act beyond
      their normal employee duties to ensure timely medication delivery to their aged
      care residents. CONCLUSIONS: This study identified pathways used to transfer
      medication information about patients being admitted to aged care facilities, and
      also immediate responses to that information. The study indicates that these
      processes, while generally satisfactory, are at times less than ideal. Health
      professionals in rural Australia may be in an ideal position to develop and
      implement effective local responses to identified problems, by activating
      interprofessional links. The study also highlights the issue of aged care staff
      acting outside their designated role in an attempt to ensure timely medication
      administration to their patients, a potentially inefficient use of limited staff
      time.

PMID- 19751095
TI  - From the bush to the big smoke--development of a hybrid urban community based
      medical education program in the Northern Territory, Australia.
AB  - CONTEXT: The Northern Territory (NT) of Australia is a unique setting for
      training medical students. This learning environment is characterised by
      Aboriginal health and an emphasis on rural and remote primary care practice. For
      over a decade the NT Clinical School (NTCS) of Flinders University has been
      teaching undergraduate medical students in the NT. Community based medical
      education (CBME) has been demonstrated to be an effective method of learning
      medicine, particularly in rural settings. As a result, it is rapidly gaining
      popularity in Australia and other countries. The NTCS adopted this model some
      years ago with the implementation of its Rural Clinical School; however, urban
      models of CBME are much less well developed than those in rural areas. There is
      considerable pressure to better incorporate CBME into medical student teaching
      environment, particularly because of the projected massive increase in student
      numbers over the next few years. To date, the community setting of urban Darwin,
      the NT capital city, has not been well utilised for medical student training.
      ISSUE: In 2008, the NTCS enrolled its first cohort of students in a new hybrid
      CBME program based in urban Darwin. This report describes the process and
      challenges involved in development of the program, including justification for a
      hybrid model and the adaptation of a rural model to an urban setting.
      Relationships were established and formalised with key partners and stakeholders,
      including GPs and general practices, Aboriginal medical services, community based
      healthcare providers and other general practice and community organisations.
      Other significant issues included curriculum development and review, development
      of learning materials and the establishment of robust evaluation methods. LESSONS
      LEARNT: Development of the CBME model in Darwin posed a number of key challenges.
      Although the experience of past rural programs was useful, a number of distinct
      differences were evident in the urban setting. Change leadership and inter
      professional collaboration were key strengths in the implementation and ongoing
      evaluation of the program. The program will provide important information about
      medical student training in urban community settings, and help inform other
      clinical schools considering the adoption of similar models.

PMID- 19751096
TI  - Novel beta-lactamase-random peptide fusion libraries for phage display selection
      of cancer cell-targeting agents suitable for enzyme prodrug therapy.
AB  - Novel phage-displayed random linear dodecapeptide (X(12)) and cysteine
      constrained decapeptide (CX(10)C) libraries constructed in fusion to the amino
      terminus of P99 beta-lactamase molecules were used for identifying beta-lactamase
      linked cancer cell-specific ligands. The size and quality of both libraries were
      comparable to the standards of other reported phage display systems. Using the
      single-round panning method based on phage DNA recovery, we identified several
      beta-lactamase fusion peptides that specifically bind to live human breast cancer
      MDA-MB-361 cells. The beta-lactamase fusion to the peptides helped in conducting
      the enzyme activity-based clone normalization and cell-binding screening in a
      very time- and cost-efficient manner. The methods were suitable for 96-well
      readout as well as microscopic imaging. The success of the biopanning was
      indicated by the presence of approximately 40% cancer cell-specific clones among
      recovered phages. One of the binding clones appeared multiple times. The cancer
      cell-binding fusion peptides also shared several significant motifs. This opens a
      new way of preparing and selecting phage display libraries. The cancer cell
      specific beta-lactamase-linked affinity reagents selected from these libraries
      can be used for any application that requires a reporter for tracking the ligand
      molecules. Furthermore, these affinity reagents have also a potential for their
      direct use in the targeted enzyme prodrug therapy of cancer.

PMID- 19751097
TI  - Expression of protein phosphatase 2B (calcineurin) subunit A isoforms in rat
      hippocampus after traumatic brain injury.
AB  - Calcineurin (CaN) is a calcium/calmodulin-dependent phosphatase directly
      activated by calcium as a result of neuronal activation that is important for
      neuronal function. CaN subunit isoforms are implicated in long-term potentiation
      (LTP), long-term depression (LTD), and structural plasticity. CaN inhibitors are
      also beneficial to cognitive outcomes in animal models of traumatic brain injury
      (TBI). There are known changes in the CaN A (CnA) subunit following fluid
      percussion injury (FPI). The CnA subunit has two isoforms: CnAalpha and CnAbeta.
      The effect of moderate controlled cortical impact (CCI) on distribution of CnA
      isoforms was examined at 2 h and 2 weeks post-injury. CnA distribution was
      assayed by immunohistochemistry and graded for non-parametric analysis. Acutely
      CnA isoforms showed reduced immunoreactivity in stratum radiatum processes of the
      ipsilateral CA1 and CA1-2. There was also a significant alteration in the
      immunoreactivity of both CnA isoforms in the ipsilateral dentate gyrus,
      predominantly within the hidden blade. Alterations in CnA isoform regional
      distribution within the CA1, CA1-2, and dentate gyrus may have significant
      implications for persistent hippocampal dysfunction following TBI, including
      dysfunction in hippocampal plasticity. Understanding alterations in CnA isoform
      distribution may help improve the targeting of current therapeutic interventions
      and/or the development of new treatments for TBI.

PMID- 19751098
TI  - Translational research in spinal cord injury: a survey of opinion from the SCI
      community.
AB  - Much like our colleagues studying neuroprotection for acute stroke, we in the
      spinal cord injury (SCI) community have witnessed the preclinical emergence of
      numerous promising neuroprotective and neuro-regenerative treatments that have
      then disappointingly failed to demonstrate convincing efficacy in clinical
      trials. In contrast to the stroke field, the SCI community lacks guidelines to
      steer the preclinical development of therapies and maximize their chance of
      success prior to translation into expensive and laborious clinical trials. We
      conducted a survey of the SCI research community to garner perspectives on the
      question of what preclinical evidence was required before translating an
      experimental treatment into clinical trials. The opinions of the 324 respondents
      about what constitutes necessary preclinical evidence before moving to human SCI
      trials revealed strong support for the demonstration of efficacy in large-animal
      models, cervical injury models, and for independent replication of promising
      results. Marked differences exist between the sentiments of the respondents and
      the translational experience of our field. A framework for guiding the
      preclinical development of novel therapies prior to human translation would be
      helpful for ensuring clinical success. Greater dialogue on this issue is
      necessary to improve our chances of successfully bringing effective treatments to
      patients with this devastating injury.

PMID- 19751099
TI  - Temporal and regional changes in IGF-1/IGF-1R signaling in the mouse brain after
      traumatic brain injury.
AB  - Although neurotrophic factors such as nerve growth factor, basic fibroblast
      growth factor, brain-derived neurotrophic factor, and neurotrophin 4/5 are
      elevated after traumatic brain injury (TBI), little is known about the endogenous
      response of insulin-like growth factor-1 (IGF-1). We evaluated IGF-1, IGF-1
      receptor (IGF-1R), and total and phosphorylated Akt (p-Akt), a known downstream
      mediator of IGF-1 signaling, using ELISA, Western blotting, and
      immunohistochemistry at 1, 6, 24, 48, and 72 h following 0.5-mm controlled
      cortical impact brain injury in adult mice. IGF-1 was transiently upregulated in
      homogenates of injured cortex at 1 h, and cells with increased IGF-1
      immunoreactivity were observed in and around the cortical contusion site up to 48
      h. IGF-1R and total Akt levels in cortical homogenates were unchanged, although
      immunohistochemistry revealed regional changes. In contrast, serine p-Akt levels
      increased significantly in homogenates at 6 h post-injury. Interestingly, delayed
      increases in vascular IGF-1R, total Akt, and p-Akt immunostaining were observed
      in and around the cortical contusion. IGF-1 and its downstream mediators were
      also upregulated in the subcortical white matter. Our findings indicate that
      moderate TBI results in a brief induction of IGF-1 and its signaling components
      in the acute post-traumatic period. This may reflect an attempt at endogenous
      neuroprotection or repair.

PMID- 19751100
TI  - Enhanced pancreatic cancer gene therapy by combination of adenoviral vector
      expressing c-erb-B2 (Her-2/neu)-targeted immunotoxin with a replication-competent
      adenovirus or etoposide.
AB  - Pancreatic cancer is the fourth leading cause of cancer-related death in the
      United States, and even under optimal therapy these patients face a poor
      prognosis. Here we report a novel gene therapy-based strategy to battle this
      disease. We show that the majority of pancreatic tumors overexpress c-erb-B2,
      which therefore might serve as a target for novel therapies. On the basis of
      these findings, we developed an adenoviral vector [Ad-e23(scFv)-PE40] encoding a
      c-erb-B2 (Her-2/neu)-targeted immunotoxin. To improve viral gene delivery we
      coinfected the therapeutic adenovirus with a replication-competent adenovirus
      (RCAd) at low doses that enhanced the transduction efficiency of the former
      virus. In addition, we show that target gene expression can be enhanced by adding
      etoposide (VP16) at nontherapeutic doses. To investigate the therapeutic efficacy
      of our approach we established a mouse model for advanced pancreatic cancer
      disease by intraperitoneal injection of pancreatic cancer cell lines, resulting
      in multifocal peritoneal xenograft tumors. Administration of Ad-e23(scFv)-PE40 in
      combination with RCAd and VP16 significantly inhibited tumor growth in mice, with
      no apparent systemic toxicity. In this study we show that c-erb-B2 might be an
      effective molecular target in the treatment of pancreatic tumors and that
      coadministration of a therapeutic c-erb-B2-targeted, non-replication-competent
      adenovirus with an RCAd and VP16 could be a powerful approach to effectively
      deliver therapeutic genes to tumors. As demonstrated, this strategy can be
      employed to effectively treat pancreatic cancer in particular, but may be
      modified to treat other types of cancer as well.

PMID- 19751101
TI  - Engineering embryonic stem-cell aggregation allows an enhanced osteogenic
      differentiation in vitro.
AB  - Pluripotent embryonic stem (ES) cells hold great promise for the field of tissue
      engineering, with numerous studies investigating differentiation into various
      cell types including cardiomyocytes, chondrocytes, and osteoblasts. Previous
      studies have detailed osteogenic differentiation via dissociated embryoid body
      (EB) culture in osteoinductive media comprising of ascorbic acid, beta
      glycerophosphate, and dexamethasone. It is hoped that these osteogenic cultures
      will have clinical application in bone tissue repair and regeneration and
      pharmacological testing. However, differentiation remains highly inefficient and
      generates heterogeneous populations. We have previously reported an engineered
      three-dimensional culture system for controlled ES cell-ES cell interaction via
      the avidin-biotin binding complex. Here we investigate the effect of such
      engineering on ES cell differentiation. Engineered EBs exhibit enhanced
      osteogenic differentiation assessed by cadherin-11, Runx2, and osteopontin
      expression, alkaline phosphatase activity, and bone nodule formation. Results
      show that cultures produced from intact EBs aggregated for 3 days generated the
      greatest levels of osteogenic differentiation when cultured in osteoinductive
      media. However, when cultured in control media, only engineered samples appeared
      to exhibit bone nodule formation. In addition, polymerase chain reaction analysis
      revealed a decrease in endoderm and ectoderm expression within engineered
      samples. This suggests that engineered ES cell aggregation has increased mesoderm
      homogeneity, contributing to enhanced osteogenic differentiation.

PMID- 19751103
TI  - Intravital molecular imaging of small-diameter tissue-engineered vascular grafts
      in mice: a feasibility study.
AB  - OBJECTIVES: Creating functional small-diameter tissue-engineered blood vessels
      has not been successful to date. Moreover, the processes underlying the in vivo
      remodeling of these grafts and the fate of cells seeded onto scaffolds remain
      unclear. Here we addressed these unmet scientific needs by using intravital
      molecular imaging to monitor the development of tissue-engineered vascular grafts
      (TEVG) implanted in mouse carotid artery. METHODS AND RESULTS: Green fluorescent
      protein-labeled human bone marrow-derived mesenchymal stem cells and cord blood
      derived endothelial progenitor cells were seeded on polyglycolic acid-poly-L
      lactic acid scaffolds to construct small-caliber TEVG that were subsequently
      implanted in the carotid artery position of nude mice (n = 9). Mice were injected
      with near-infrared agents and imaged using intravital fluorescence microscope at
      0, 7, and 35 days to validate in vivo the TEVG remodeling capability
      (Prosense680; VisEn, Woburn, MA) and patency (Angiosense750; VisEn). Imaging
      coregistered strong proteolytic activity and blood flow through anastomoses at
      both 7 and 35 days postimplantation. In addition, image analyses showed green
      fluorescent protein signal produced from mesenchymal stem cell up to 35 days
      postimplantation. Comprehensive correlative histopathological analyses
      corroborated intravital imaging findings. CONCLUSIONS: Multispectral imaging
      offers simultaneous characterization of in vivo remodeling enzyme activity,
      functionality, and cell fate of viable small-caliber TEVG.

PMID- 19751104
TI  - Treatment strategies for central venous catheter infections.
AB  - Intravascular catheters are essential in most hospital units. These devices are
      the most common source of nosocomial bloodstream infections. Catheter-related
      bloodstream infections (CR-BSI) are associated with increased morbidity and
      mortality, prolonged hospitalization, and increased costs. CR-BSI can be
      diagnosed by different bacteriologic techniques, some of which can be performed
      in situ without withdrawing the device. Prevention strategies should aim to avoid
      extra- and endoluminal contamination. The management of CR-BSI includes catheter
      withdrawal and an appropriate antibiotic, which depends on the patient's clinical
      situation and on etiologic factors. Glycopeptide antibiotics are widely used for
      empirical treatment because of the high prevalence of staphylococcal infections.
      Antibiotic therapy should be reassessed when culture and sensitivity results are
      known.

PMID- 19751105
TI  - Is zoledronic acid an anticancer drug?

PMID- 19751109
TI  - Developmental potential of bovine hand-made clone embryos reconstructed by
      aggregation or fusion with distinct cytoplasmic volumes.
AB  - Animal cloning has been associated with developmental abnormalities, with the
      level of heteroplasmy caused by the procedure being one of its potential limiting
      factors. The aim of this study was to determine the effect of the fusion of
      hemicytoplasts or aggregation of hemiembryos, varying the final cytoplasmic
      volume, on development and cell density of embryos produced by hand-made cloning
      (HMC), parthenogenesis or by in vitro fertilization (IVF). One or two enucleated
      hemicytoplasts were paired and fused with one skin somatic cell. Activated clone
      and zona-free parthenote embryos and hemiembryos were in vitro cultured in the
      well-of-the-well (WOW) system, being allocated to one of six experimental groups,
      on a per WOW basis: single clone or parthenote hemiembryos (1 x 50%); aggregation
      of two (2 x 50%), three (3 x 50%), or four (4 x 50%) clone or parthenote
      hemiembryos; single clone or parthenote embryos (1 x 100%); or aggregation of two
      clone or parthenote embryos (2 x 100%). Control zona-intact parthenote or IVF
      embryos were in vitro cultured in four-well dishes. Results indicated that the
      increase in the number of aggregated structures within each WOW was followed by a
      linear increase in cleavage, blastocyst rate, and cell density. The increase in
      cytoplasmic volume, either by fusion or by aggregation, had a positive effect on
      embryo development, supporting the establishment of pregnancies and the birth of
      a viable clone calf after transfer to recipients. However, embryo aggregation did
      not improve development on a hemicytoplast basis, except for the aggregation of
      two clone embryos.

PMID- 19751110
TI  - Transcript levels of several epigenome regulatory genes in bovine somatic donor
      cells are not correlated with their cloning efficiency.
AB  - Among many factors that potentially affect somatic cell nuclear transfer (SCNT)
      embryo development is the donor cell itself. Cloning potentials of somatic donor
      cells vary greatly, possibly because the cells have different capacities to be
      reprogrammed by ooplasma. It is therefore intriguing to identify factors that
      regulate the reprogrammability of somatic donor cells. Gene expression analysis
      is a widely used tool to investigate underlying mechanisms of various phenotypes.
      In this study, we conducted a retrospective analysis investigating whether donor
      cell lines with distinct cloning efficiencies express different levels of genes
      involved in epigenetic reprogramming including histone deacetylase-1 (HDAC1), -2
      (HDAC2); DNA methyltransferase-1 (DNMT1), -3a (DNMT3a),-3b (DNMT3b), and the
      bovine homolog of yeast sucrose nonfermenting-2 (SNF2L), a SWI/SNF family of
      ATPases. Cell samples from 12 bovine donor cell lines were collected at the time
      of nuclear transfer experiments and expression levels of the genes were measured
      using quantitative polymerase chain reaction (PCR). Our results show that there
      are no significant differences in expression levels of these genes between donor
      cell lines of high and low cloning efficiency defined as live calving rates,
      although inverse correlations are observed between in vitro embryo developmental
      rates and expression levels of HDAC2 and SNF2L. We also show that selection of
      stable reference genes is important for relative quantification, and different
      batches of cells can have different gene expression patterns. In summary, we
      demonstrate that expression levels of these epigenome regulatory genes in bovine
      donor cells are not correlated with cloning potential. The experimental design
      and data analysis method reported here can be applied to study any genes
      expressed in donor cells.

PMID- 19751111
TI  - Transcriptomic analysis identifies Foxo3A as a novel transcription factor
      regulating mesenchymal stem cell chrondrogenic differentiation.
AB  - Multipotent mesenchymal stromal cells (MSC) are progenitor cells able to
      differentiate into several lineages including chondrocytes, and thus represent a
      suitable source of cells for cartilage engineering. However, the control of MSC
      differentiation to hypertrophy is a crucial step for the clinical application of
      MSC in cartilage repair where a stable chondrogenic phenotype without transition
      to terminal differentiation is the goal to achieve. This study aims at
      identifying new factors that may regulate this process. Using microarrays, we
      compared the transcriptional profiles of human MSC and MSC-derived chondrocytes
      obtained after culture in micropellets. After chondrogenesis induction, 676 genes
      were upregulated, among which five transcription factors not yet associated with
      chondrocyte differentiation of adult stem cells. These factors, in particular
      Foxo3A, are strongly expressed at day 21 and in mature chondrocytes. We
      investigated the role of Foxo3A using RNA interference. Our results revealed an
      important role of Foxo3A in the differentiation process of MSC toward
      chondrogenic fate, both in early and late stages. Indeed, stable Foxo3A knockdown
      tends to increase cell survival and decrease apoptosis, mainly in early stages of
      chondrogenesis. Importantly, we show that the loss of Foxo3A in MSC results in an
      increased expression level of markers specific for mature (aggrecan, collagen II)
      and hypertrophic (collagen X) chondrocytes. Therefore, our findings suggest that
      upregulation of Foxo3A over the course of chondrogenic differentiation plays a
      dual role, mainly inhibiting the differentiation process toward hypertrophy and
      promoting cell apoptosis.

PMID- 19751112
TI  - BMP-11 and myostatin support undifferentiated growth of human embryonic stem
      cells in feeder-free cultures.
AB  - BMP-11/GDF-11 and Myostatin/GDF-8 are both members of the TGF-beta superfamily
      that can activate SMAD2/3 phosphorylation via the type I receptors ALK4, ALK5, or
      ALK7. We tested the ability of BMP-11 and Myostatin to promote self-renewal of
      human embryonic stem cells (hESC) under feeder-free and serum-free culture
      conditions in short term (1 week) and medium term cultures (10 weeks). We show
      that hESC cultured in serum-free medium supplemented with either 20 ng/mL
      Myostatin or 20 ng/mL BMP-11 maintain the colony and cellular morphology of
      undifferentiated hESC, maintain POU5f1, NANOG, TRA-1-60, and SSEA4 expression,
      and display increased SMAD2/3 phosphorylation, similar to hESC cultured in mouse
      embryonic fibroblast feeder-CM or 20 ng/mL Activin-A. The type I TGF-beta
      receptor inhibitor SB431542 totally inhibited the maintenance activity of both
      Myostatin or BMP-11 supplemented medium. Our data show that members of the TGF
      beta superfamily, other than Activin-A and GDF3, are able to maintain hES cells
      in an undifferentiated state under feeder free conditions.

PMID- 19751113
TI  - Establishment of an exogenous LIF-free culture system for mouse embryonic stem
      cells.
AB  - Mouse embryonic stem cells (mESCs) have played a key role in the newly emerging
      fields of stem cell research. The traditional derivation and culture of mESCs
      have been based on the use of mouse embryonic fibroblasts (MEFs) treated with
      exogenous leukemia inhibitory factor (LIF). However, the rapid senescence of
      MEFs, coupled with the high cost of LIF, has significantly hampered the
      widespread use of mESCs in stem cell research. Thus, we present a novel exogenous
      LIF-free culture system for general mESCs applications, comprising fibroblast
      like cells derived from the rabbit spleen (RSFs). We demonstrated that mESCs
      cultured on RSFs (mESCs-RSFs) maintained all mESC features after prolonged LIF
      free culture, including alkaline phosphatase, cell surface markers (SSEA-1),
      molecular markers (OCT-4, NANOG, TERT, REX-1), karyotype, and pluripotency. The
      high expression level of both LIF and WNT3A in the RSFs may account for their
      ability to maintain mESCs without exogenous LIF. Moreover, this exogenous LIF
      free culture system was verified to be of microbiological quality through
      analysis with electron transmission microscopy.

PMID- 19751114
TI  - Evaluation of in vitro cultured rat oocytes, from different strains, by spindle
      morphology and maturation-promoting-factor activity combined with nuclear
      transfer experiments.
AB  - Although successful nuclear transfer (NT) has been reported in the rat 6 years
      ago, somatic cell nuclear transfer (SCNT) in the rat could not be repeated. Our
      experiments with rat SCNT reveal the difficulties related to rat cloning. We
      first focussed on the most appropriate rat strain that could be used as an oocyte
      donor. Then we describe how rat oocytes can be kept in a nonactivated state
      during in vitro culture, because the latter undergo spontaneous partial
      activation through rapid extrusion of the second polar body after isolation from
      the oviduct. In the SCNT experiments performed with the one-step manipulation
      technique it was possible to produce rat embryos, which developed in vivo up to
      the blastocyst stage. In addition, we identified the implantation sites of SCNT
      rat embryos reconstructed with Sprague-Dawley (SD) oocytes. Furthermore,
      different rat strains were used as oocyte donors and their oocytes were cultured
      under different conditions to establish a stable nonactivating oocyte culture
      system. The ratio of activated to nonactivated oocytes was measured by spindle
      stability and maturation promoting factor (MPF) activity. These measurements
      indicated that a substrain of the SD rat strain, the so-called OFA-SD strain, is
      the one providing the most stable oocytes, when their oocytes are cultured in the
      presence of the proteasome inhibitor MG132. However, it was not possible to
      obtain any implantation sites with reconstructed oocytes derived from the OFA-SD
      strain transferred to foster mothers. This goal was not achieved, even when the
      trichostatin A (TSA) treatment was used, which is known to enhance the cloning
      efficiency of reconstructed mouse, porcine, bovine, and rabbit oocytes both in
      vitro and in vivo by enhancing the reprogramming efficiency of the recipient
      nucleus.

PMID- 19751115
TI  - Efficacy and tolerability of amlodipine/valsartan combination therapy in
      hypertensive patients not adequately controlled on amlodipine monotherapy.
AB  - ABSTRACT (ARB), in essential hypertensive patients not adequately controlled by
      amlodipine monotherapy. METHODS: This was a multi-centre, randomised, double
      blind, active-controlled study in patients with essential hypertension. After a
      washout period followed by a single-blind amlodipine 10 mg run-in period,
      patients with mean sitting diastolic blood pressure (msDBP) > or =90 mmHg and
      <110 mmHg were randomised to receive amlodipine/valsartan (10/160 mg o.d.) or
      amlodipine (10 mg o.d.) for 8 weeks. TRIAL REGISTRATION NUMBER: NCT00171002. MAIN
      OUTCOME MEASURES: The primary efficacy variable was change from baseline in msDBP
      at study endpoint. Secondary efficacy variables were change from baseline in mean
      sitting systolic blood pressure (msSBP), responder rate (msDBP <90 mmHg or > or
      =10 mmHg reduction from baseline) and DBP control rate (msDBP <90 mmHg). RESULTS:
      Of the 1283 patients enrolled in single-blind period, 944 were randomised to
      receive amlodipine/valsartan 10/160 mg (n = 473) and amlodipine 10 mg (n = 471).
      Statistically significant greater reductions (p < 0.0001) from baseline in
      msSBP/msDBP were observed with combination therapy (12.9/11.4 mmHg) compared to
      monotherapy (10.0/9.3 mmHg). Responder rate was significantly greater (p =
      0.0011) with combination therapy (79.0%) compared to monotherapy (70.1%). The
      percentage of patients with controlled DBP was also significantly (p < 0.0001)
      higher with combination therapy (77.8%) compared to monotherapy (66.5%).
      Incidence of peripheral oedema was slightly higher with amlodipine monotherapy
      (9.4%) compared to combination therapy (7.6%). CONCLUSION: The combination of
      amlodipine/valsartan in this 8-week double-blind study provided additional BP
      control and was well tolerated in patients inadequately controlled with
      amlodipine monotherapy. Results should be interpreted with the knowledge that
      study entry criteria may limit application to a wider population.

PMID- 19751116
TI  - Improved glycaemic control with BIAsp 30 in insulin-naive type 2 diabetes
      patients inadequately controlled on oral antidiabetics: subgroup analysis from
      the IMPROVE study.
AB  - OBJECTIVE: The aim of this subanalysis of the IMPROVE study was to evaluate the
      safety and effectiveness of initiating biphasic insulin aspart 30/70 (BIAsp 30)
      in type 2 diabetes patients uncontrolled on oral antidiabetic drugs (OADs).
      METHODS: IMPROVE is a 26-week, open-label, non-randomised, international
      observational study in type 2 diabetes patients prescribed BIAsp 30 in routine
      clinical practice. The total cohort comprised 52 419 patients from various pre
      study therapies. Here results from the subgroup of previously insulin-naive
      patients are reported. Changes in glycated haemoglobin (HbA(1c)), fasting blood
      glucose (FBG), postprandial blood glucose (PPBG), weight, dose, proportion of
      patients achieving HbA(1c) < 7.0%, and rates of major and minor hypoglycaemic
      events were recorded. Treatment satisfaction was assessed using a validated
      questionnaire. RESULTS: A total of 29 160 insulin-naive patients were included;
      mean age 55.6 years, diabetes duration 7.3 years, baseline HbA(1c) 9.24%.
      Significant reductions were seen for HbA(1c) (-2.12%; p < 0.0001), FBG (-4.07
      mmol/L; p < 0.0001) and PPBG after all meals (mean: -5.27 mmol/L; p < 0.0001);
      39.2% of patients achieved HbA(1c) < 7.0% without hypoglycaemia. Better glycaemic
      control was seen in patients treated with BIAsp 30 twice-daily (BID) both at
      baseline and final visit, or BID at baseline and three-times daily at final
      visit, compared with other regimens. The rate of major hypoglycaemic events
      decreased significantly, while the rate of minor hypoglycaemic events increased.
      Better glycaemic control and a lower rate of minor hypoglycaemia were observed in
      patients using BIAsp 30 without OADs than with OADs. There was no clinically
      relevant change in weight (-0.07 kg; p < 0.0001). At final visit, 59.7% of
      patients were extremely/very satisfied with treatment, compared with 10.2% at
      baseline. CONCLUSIONS: This open-label, non-randomised, observational study
      demonstrated that initiating insulin therapy with BIAsp 30 significantly improved
      glycaemic control in insulin-naive patients previously poorly controlled on OADs.
      The rate of major hypoglycaemia was reduced and treatment satisfaction increased
      after initiation of BIAsp 30. Furthermore, better glycaemic control was achieved
      with BIAsp 30 without OAD compared to with OAD.

PMID- 19751117
TI  - Simplicity of use: a critical feature for widespread adoption of diagnostic
      technologies in low-resource settings.

PMID- 19751119
TI  - Cardioblate surgical ablation system.
AB  - Atrial fibrillation is the most common sustained arrhythmia and represents a
      considerable health burden. In recent years there has been an increased interest
      in ablation treatment of atrial fibrillation. The Cardioblate surgical ablation
      system offers a complete system for surgical ablation as a concomitant or lone
      atrial fibrillation procedure. Saline-irrigated radiofrequency energy is used to
      produce electrically isolating lines in the atrial tissue. A range of disposable
      devices can be connected to the generator. A comprehensive review of the devices
      and the results achieved with the system is given. The system is compared with
      other alternative energy sources and to the Cox-Maze procedure.

PMID- 19751120
TI  - Crux vena cava filter.
AB  - Inferior vena cava filters are widely accepted for pulmonary embolic prophylaxis
      in high-risk patients with contraindications to anticoagulation. While long-term
      complications have been associated with permanent filters, retrievable filters
      are now available and have resulted in the rapid expansion of this technology.
      Nonetheless, complications are still reported with optional filters. Furthermore,
      device tilting and thrombus load may prevent retrieval in up to 30% of patients,
      thereby eliminating the benefits of this technology. The Crux vena cava filter is
      a novel, self-centering, low-profile filter that is designed for ease of
      delivery, retrievability and improved efficacy while limiting fatigue-related
      device complications. This device has been proven safe and user-friendly in an
      ovine model and has recently been implanted in human subjects.

PMID- 19751121
TI  - Stereotaxis Niobe magnetic navigation system for endocardial catheter ablation
      and gastrointestinal capsule endoscopy.
AB  - The use of robotic instruments capable of assisting medical staff during
      interventional or diagnostic procedures is growing rapidly today. Recently, a
      robotic system (Niobe, Stereotaxis Inc., USA) has been developed for navigating
      magnetically enabled tools inside the human body by controlling a magnetic field.
      This paper reports the fundamentals of this technology and reviews its
      application in two specific medical fields, cardiology and gastroenterology, in
      which its uses are different and are at dissimilar stages of development. In the
      first case, the system is already approved and employed for clinical treatments,
      such as magnetic steering of endocardial catheters for atrial fibrillation
      ablation, which is specifically considered in this article. In the second case,
      initial investigations are being performed today to study the potential magnetic
      maneuverability of ingestible video capsules adopted for endoscopic explorations
      of the digestive tract. This paper reviews current achievements and highlights
      future challenges related to each of these applications.

PMID- 19751122
TI  - Carbon nanotubes in scaffolds for tissue engineering.
AB  - Carbon nanotubes are hollow graphitic cylinders of nanoscale dimensions. They are
      electrically conductive, chemically and thermally stable, and exceptionally
      strong. Given this unique combination of properties there has been much interest
      in carbon nanotubes, and finding applications for them. One application where
      this combination of properties may prove useful is in the area of tissue
      regeneration, incorporating carbon nanotubes into scaffolds for tissue
      engineering. It is believed that carbon nanotubes may improve scaffold properties
      and enhance tissue regeneration. This report aims to discuss the suitability of
      carbon nanotubes as a biomaterial for scaffold production, and the fabrication,
      properties and performance of carbon nanotube-based scaffolds.

PMID- 19751123
TI  - Computer-assisted total hip arthroplasty: coding the next generation of
      navigation systems for orthopedic surgery.
AB  - This article outlines the scientific basis and a state-of-the-art application of
      computer-assisted orthopedic surgery in total hip arthroplasty (THA) and provides
      a future perspective on this technology. Computer-assisted orthopedic surgery in
      primary THA has the potential to couple 3D simulations with real-time evaluations
      of surgical performance, which has brought these developments from the research
      laboratory all the way to clinical use. Nonimage- or imageless-based navigation
      systems without the need for additional pre- or intra-operative image acquisition
      have stood the test to significantly reduce the variability in positioning the
      acetabular component and have shown precise measurement of leg length and offset
      changes during THA. More recently, computer-assisted orthopedic surgery systems
      have opened a new frontier for accurate surgical practice in minimally invasive,
      tissue-preserving THA. The future generation of imageless navigation systems will
      switch from simple measurement tasks to real navigation tools. These software
      algorithms will consider the cup and stem as components of a coupled
      biomechanical system, navigating the orthopedic surgeon to find an optimized
      complementary component orientation rather than target values intraoperatively,
      and are expected to have a high impact on clinical practice and postoperative
      functionality in modern THA.

PMID- 19751125
TI  - Adipose tissue engineering: state of the art, recent advances and innovative
      approaches.
AB  - Adipose tissue is a highly specialized connective tissue found either in white or
      brown forms, the white form being the most abundant in adult humans. Loss or
      damage of white adipose tissue due to aging or pathological conditions needs
      reconstructive approaches. To date, two main strategies are being investigated
      for generating functional adipose tissue: autologous tissue/cell transplantation
      and adipose tissue engineering. Free-fat transplantation rarely achieves
      sufficient tissue augmentation owing to delayed neovascularization, with
      subsequent cell necrosis and graft volume shrinkage. Tissue engineering
      approaches represent, instead, a more suitable alternative for adipose tissue
      regeneration; they can be performed either with in situ or de novo adipogenesis.
      In situ adipogenesis or transplantation of encapsulated cells can be useful in
      healing small-volume defects, whereas restoration of large defects, where
      vascularization and a rapid volumetric gain are strict requirements, needs de
      novo strategies with 3D scaffold/filling matrix combinations. For adipose tissue
      engineering, the use of adult mesenchymal stem cells (both adipose- and bone
      marrow-derived stem cells) or of preadipocytes is preferred to the use of mature
      adipocytes, which have low expandability and poor ability for volume retention.
      This review intends to assemble and describe recent work on this topic,
      critically presenting successes obtained and drawbacks faced to date.

PMID- 19751124
TI  - New directions in nanofibrous scaffolds for soft tissue engineering and
      regeneration.
AB  - This review focuses on the role of nanostructure and nanoscale materials for
      tissue engineering applications. We detail a scaffold production method
      (electrospinning) for the production of nanofiber-based scaffolds that can
      approximate many critical features of the normal cellular microenvironment, and
      so foster and direct tissue formation. Further, we describe new and emerging
      methods to increase the applicability of these scaffolds for in vitro and in vivo
      application. This discussion includes a focus on methods to further functionalize
      scaffolds to promote cell infiltration, methods to tune scaffold mechanics to
      meet in vivo demands and methods to control the release of pharmaceuticals and
      other biologic agents to modulate the wound environment and foster tissue
      regeneration. This review provides a perspective on the state-of-the-art
      production, application and functionalization of these unique nanofibrous
      structures, and outlines future directions in this growing field.

PMID- 19751126
TI  - Antibacterial surfaces for biomedical devices.
AB  - Despite considerable research and development efforts, the problem of infections
      related to biomedical devices and implants persists. Bacteria evidently can
      readily colonize surfaces of synthetic materials, such as those used for the
      fabrication of catheters, hip and knee implants, and many other devices. As the
      growing colony encapsulates itself with a protective exocellular bacterial
      polysaccharide layer, the biofilm becomes much harder to combat than circulating
      bacteria. Thus, there is a strong need to mitigate bacterial colonization by
      equipping the surfaces of biomedical devices and implants with features such as
      surface chemistry and surface roughness that are unfavorable for bacterial
      attachment. Here we review a number of strategies used for the design of
      antibacterial coatings. We also discuss specific issues that arise from using
      various types of coatings.

PMID- 19751127
TI  - Quantitative evaluation of Alzheimer's disease.
AB  - Alzheimer's disease (AD) can be definitively diagnosed only by histopathologic
      examination of brain tissue; the identification and differential diagnosis of AD
      is especially challenging in its early stages. Neuroimaging is playing an
      increasingly relevant role in the identification and quantification of AD in
      vivo, especially in the preclinical stages, when therapeutic intervention could
      be more effective. Neuroimaging enables quantification of brain volume loss
      (structural imaging), detection of early cerebral dysfunction (functional
      imaging), probing into the finest cerebral structures (microstructural imaging),
      and investigation of amyloid plaque and neurofibrillary tangle build-up (amyloid
      imaging). Throughout the years, several imaging tools have been developed,
      ranging from simple visual rating scales to sophisticated computerized
      algorithms. As recently revised criteria for AD require quantitative evaluation
      of biomarkers mostly based on imaging, this paper provides an overview of the
      main neuroimaging tools which might be used presently or in the future in routine
      clinical practice for AD diagnosis.

PMID- 19751139
TI  - Clinical value of a competitive NT-proBNP enzyme immunoassay compared to the
      Roche NT-proBNP platform.

PMID- 19751140
TI  - Impact of calibration fitting models on the clinical value of chromogranin A.
AB  - BACKGROUND: The clinical relevance of chromogranin A (CgA) concentrations depends
      on the analytical performance of the assay. The goal of the present study was to
      define the clinical involvements in CgA calibration models by evaluating the
      confidence intervals (CIs) for values from patients who were undergoing
      monitoring for disease. METHODS: Thirty calibration curves for the CgA assay
      [immunoradiometric assay (IRMA), (CIS-BIO)] were built using linear regression
      (LR), and four-parameter logistic models were used to estimate CIs for patient
      concentrations. RESULTS: We reported the inadequacy of the LR curve estimation
      procedure. We showed: 1) no evidence that the straight calibration line could fit
      the average responses, 2) non-constant and non-uniform variance of the replicated
      calibration responses. All tests performed in the analysis of variance and CI
      calculation for the calibration curve should be invalidated. The four-parameter
      logistic function yielded results for 16 curves only; this result could be due to
      the low number and inappropriate concentration of calibrators. This suggests that
      some aspects of the assay design should be reviewed. However, using the variance
      function estimated in this model, we could assess the CI for calibration curves
      and patient samples. CONCLUSIONS: We showed that the four-parameter logistic
      calibration model with estimated variance function should better support clinical
      interpretation of marker concentration changes in patients serially tested.

PMID- 19751141
TI  - HbA1c measurements from dried blood spots: validation and patient satisfaction.
AB  - BACKGROUND: This study evaluates HbA1c measurements from dried blood spots
      collected on filter paper and compares HbA1c from filter paper (capillary blood)
      with HbA1c measured in venous blood. METHODS: Patient satisfaction was evaluated
      using a questionnaire. The performance with the filter paper method was assessed
      by comparing HbA1c results from EDTA-blood samples obtained via dried blood spots
      with HbA1c results obtained with freshly hemolyzed blood (routine HbA1c). Adult
      patients visiting the outpatient clinic for HbA1c analyses were recruited for the
      evaluation of dried blood spot sampling at home. Laboratory personnel collected a
      capillary blood sample on filter paper as well as a venous EDTA-blood sample. The
      participants collected another capillary blood sample at home and sent the dried
      filter paper back to the laboratory. Samples were analyzed with an
      immunoturbidimetric assay. RESULTS: Between-filter coefficient of variation was
      1.8%. Filter paper HbA1c increased slightly during storage, particularly during
      the first 5 days. Filter paper HbA1c highly correlated with routine HbA1c
      (r=0.987). The evaluation of samples collected at home showed comparable HbA1c
      values by filter paper and routine sampling methods (n=93). Eighty-three percent
      of participants said they would like the filter method to be brought into
      practice. CONCLUSIONS: Home HbA1c sampling on filter paper is an acceptable
      sampling alternative for analysis of HbA1c.

PMID- 19751142
TI  - Pre-transplant serum concentrations of anti-endothelial cell antibody in panel
      reactive antibody negative renal recipients and its impact on acute rejection.
AB  - BACKGROUND: Endothelial cell antigens are important targets in acute rejection
      (AR). Our goal was to measure the serum concentrations of pre-transplant anti
      endothelial cell antibody (AECA) in panel reactive antibody (PRA) negative
      recipients and its impact on AR within 6 months following renal transplantation.
      METHODS: We retrospectively examined pre-transplant sera from 392 patients using
      cellular enzyme linked immunosorbent assay (ELISA) with substrate from a
      permanent endothelial cell line EAhy926. Equal volumes of serum from 40 healthy
      volunteers were mixed and used as the negative control. RESULTS: The positive
      rate of AECA was 15.8%. There were no significant differences with respect to
      age, gender, original disease, dialysis history, immune suppressive regimen,
      cytomegalovirus (CMV) antigen positive rate, complement dependent cytotoxicity
      (CDC) level and soluble CD30 (sCD30) levels between the AECA positive group and
      AECA negative group. AR rate in the AECA positive group was higher than that in
      the AECA negative group (35.5% vs. 22.4%, p=0.023). The AECA positive patients
      had significantly higher rates of acute grade II T-cell mediated rejection (TMR)
      and acute antibody mediated rejection (AMR) compared with AECA negative patients.
      The concentrations of sCD30, and AECA were independent risk factors for AR within
      6 months; the odds ratios were 7.005 and 2.469, respectively. CONCLUSIONS:
      Positive AECA was an independent risk factor for AR and appeared to correlate
      with relatively severe rejection subtypes.

PMID- 19751143
TI  - Should gender-related reference values be used for total bilirubin?

PMID- 19751144
TI  - Editorial.

PMID- 19751145
TI  - Genetic diversity of HIV type 1 along the coastal strip of Kenya.
AB  - A study on the genetic diversity of HIV-1 subtypes present along the coastal
      strip of Kenya, i.e., Kilifi, Mombasa, Msambweni, and Malindi districts, was
      carried out. DNA sequences for regions encoding a portion of the env-gp41 region
      of the virus were generated by PCR and sequenced directly. Eighty six samples
      that were successfully sequenced were analyzed. From the analysis, 86% (74) were
      subtype A1, 5% (4) were subtype C, 8% (7) were subtype D, and 1% (1) was subtype
      G. This study shows that HIV-1 subtype A1 is the most dominant subtype in
      circulation in this region.

PMID- 19751146
TI  - Use of massive parallel pyrosequencing for near full-length characterization of a
      unique HIV Type 1 BF recombinant associated with a fatal primary infection.
AB  - Near full length genome characterization of a BF recombinant from a patient who
      died from multiorgan failure during HIV-1 seroconversion is reported. Massive
      parallel pyrosequencing was used with the shotgun approach. Intrahost genetic
      variability along the whole genome was calculated and coreceptor usage of viral
      quasispecies was predicted. A consensus sequence was established to perform
      subtype assignment, phylogenetic analysis, and recombination tests. The sequence
      clustered with two recently described BF unique recombinant forms from Brazil,
      consistent with the recombination pattern, yielding breakpoints located at the
      same positions, with the exception of the second env breakpoint. The actual
      prevalence of recombinant forms is probably underestimated if partial genomic
      regions are considered. Here the first full length BF recombinant from Italy is
      described, together with an evaluation of quasispecies heterogeneity. Our data
      provide evidence that next generation sequencing may provide a major contribution
      to HIV-1 molecular epidemiology and to the comprehension of intrapatient
      heterogeneity.

PMID- 19751147
TI  - Preconditioning promotes survival and angiomyogenic potential of mesenchymal stem
      cells in the infarcted heart via NF-kappaB signaling.
AB  - We proposed that pharmacological manipulation of mesenchymal stem cells (MSCs)
      with diazoxide enhanced their survival and regenerative potential via NFkappaB
      regulation. MSCs preconditioned ((PC)MSCs) with diazoxide and later subjected to
      oxidant stress with 100 micromol/L H(2)O(2) either immediately or after 24 h
      exhibited higher survival (p < 0.01 vs nonpreconditioned MSCs; (Non-PC)MSCs) with
      concomitantly increased phosphorylation of PI3K, Akt, GSK3beta (cytoplasmic), and
      NF-kappaB (p65) (nuclear). Akt kinase activity was determined as a function of
      GSK3beta activity. Pretreatment of (PC)MSCs with Wortmannin (Wt), NEMO-binding
      domain (NBD), or NF-kappaB (p50) siRNA abolished NF-kappaB (p65) activity.
      Preconditioning increased NF-kappaB-dependent elevation of secretable growth
      factors associated with their paracrine effects. Inhibition of PI3K activity with
      Wt reduced (PC)MSCs viability at both early and 24 h time-points. However,
      inhibition of NF-kappaB reduced viability of (PC)MSCs only at 24 h time-point.
      For in vivo studies, DMEM without cells (group-1) or containing 1 x 10(6) male
      (Non-PC)MSCs (group-2), (PC)MSCs (group-3), (PC)MSCs pretreated with Wortmannin
      (group-4) or NF-kappaB decoy (group-5) were transplanted in a female rat model of
      acute myocardial infarction. Group-3 showed highest cell survival and growth
      factor expression, increased angiomyogenesis, and functional improvement. We
      conclude that activation of NF-kappaB by preconditioning promoted (PC)MSCs
      survival and angiomyogenic potential in the infarcted heart.

PMID- 19751148
TI  - Long-term luciferase expression monitored by bioluminescence imaging after adeno
      associated virus-mediated fetal gene delivery in rhesus monkeys (Macaca mulatta).
AB  - The safety and efficiency of fetal adeno-associated virus (AAV) gene delivery in
      rhesus monkeys and long-term monitoring of transgene expression by
      bioluminescence imaging (BLI) were evaluated. Early second-trimester fetal
      monkeys were administered AAV2/5, AAV2/9, or AAV2/10 vector supernatant
      preparations expressing firefly luciferase under the control of the
      cytomegalovirus promoter, using an intrathoracic (n = 6) or intramyocardial (n =
      6) approach and established ultrasound-guided techniques. Postnatal BLI was
      performed monthly up to 6 months postnatal age (n = 12) and then every 3 months
      thereafter to monitor transgene expression up to 24 months postnatal age (27
      months after gene transfer; n = 6). All AAV serotypes showed greater than 1.0 x
      10(9) photons/sec at all time points evaluated with limited biodistribution to
      nontargeted anatomical sites. The highest levels of bioluminescence (photons per
      second) observed were noted with AAV2/9 and AAV2/10 when the three vector
      constructs were compared. To correlate in vivo findings at the tissue level,
      specimens were collected from selected animals and analyzed. Three-dimensional
      reconstruction showed that firefly luciferase expression was consistent with
      imaging and morphometric measures. These findings suggest that (1) high levels of
      AAV-mediated firefly luciferase expression can be found after fetal AAV gene
      transfer and without any evidence of adverse effects; (2) the intercostal
      muscles, myocardium, and muscular component of the diaphragm of developing
      fetuses are readily transduced with AAV2/5, AAV2/9, or AAV2/10; and (3) postnatal
      outcomes and long-term luciferase expression can be effectively monitored by BLI
      in young rhesus monkeys.

PMID- 19751149
TI  - Risk factors, clinical features, and outcomes of listeriosis in solid-organ
      transplant recipients: a matched case-control study.
AB  - BACKGROUND: Solid-organ transplant (SOT) recipients are classically considered to
      be at increased risk for listeriosis. However, risk factors for this infection
      have not been assessed. METHODS: We carried out a multicenter, matched case
      control study (1:2 ratio) from January 1995 through December 2007. Control
      subjects were matched for center, transplant type, and timing. Conditional
      logistic regression was performed to identify independent risk factors. Clinical
      features and outcomes for all case patients were reviewed. RESULTS: Thirty
      patients (0.12%) with cases of listeriosis were identified among 25,997 SOT
      recipients at 15 Spanish transplant centers. In a comparison of case patients
      with 60 matched control subjects, the following independent risk factors for
      listeriosis were identified: diabetes mellitus (odds ratio [OR], 5.6; 95%
      confidence interval [CI], 1.6-19.6; ), P = .007 history of cytomegalovirus
      infection or disease within the preceding 6 months (OR, 35.9; 95% CI, 2.1-620; P
      = .014), receipt of high-dose prednisone within the preceding 6 months (OR, 6.2;
      95% CI, 1.8-21.1; P = .003), and trimethoprim-sulfamethoxazole (TMP-SMZ)
      prophylaxis (OR, 0.07; 95% CI, 0.006-0.76; P = .029). Twenty-six patients (86.7%)
      had bacteremia, and 7 had shock at presentation. Other manifestations included
      meningoencephalitis (10 cases), spontaneous peritonitis (2), pleural empyema (1),
      brain abscesses (1), and liver abscesses (1). The 30-day mortality rate was 26.7%
      (8 of 30 patients died). CONCLUSIONS: Listeriosis in SOT recipients is uncommon
      but causes high mortality. Diabetes mellitus, cytomegalovirus infection or
      disease, and receipt of high-dose steroids are independent risk factors for this
      infection, whereas TMP-SMZ prophylaxis is a protective factor.

PMID- 19751150
TI  - Toward the individualization of cytomegalovirus control after solid-organ
      transplantation: the importance of the "individual pathogenic balance".

PMID- 19751151
TI  - Impact of genetic polymorphisms in cytomegalovirus glycoprotein B on outcomes in
      solid-organ transplant recipients with cytomegalovirus disease.
AB  - BACKGROUND: It is unknown whether specific viral polymorphisms affect in vivo
      therapeutic response in patients with cytomegalovirus (CMV) disease.
      Polymorphisms in the CMV glycoprotein B (gB) gene allow discrimination of 4
      distinct genotypes (gB1-gB4). We assessed the influence of gB genotypes on the
      clinical and virologic outcome of CMV disease. METHODS: Solid-organ transplant
      recipients enrolled in a multicenter trial of CMV disease treatment (VICTOR
      study) were included in this study. CMV gB genotyping was performed using
      quantitative real-time polymerase chain reaction at day 0 (start of antiviral
      therapy). RESULTS: Among 239 patients with CMV disease, the prevalence of gB
      strain types was 26% for gB1, 10% for gB2, 10% for gB3, and 5% for gB4, whereas
      mixed infections were present in 49%. Donor-seropositive/recipient-seropositive
      patients were more likely to have mixed gB infection than donor
      seropositive/recipient-seronegative patients (40% vs. 12%; P = .001). Median
      baseline viral loads were higher and time to viral eradication was longer ( P =
      .006 and P = .026 , respectively) for mixed infection versus infection with a
      single genotype. In a multivariate model, mixed gB infection was a significant
      predictor of failure to eradicate virus by day 21 (mixed vs single genotype; odds
      ratio, 2.66; 95% confidence interval, 1.31-5.38; P = .007 ) after controlling for
      baseline viral load, CMV serostatus at baseline, ganciclovir resistance, and
      antiviral treatment. No effect of gB genotype was seen on virologic or clinical
      CMV recurrence. CONCLUSIONS: No specific gB genotype appears to confer a specific
      CMV virulence advantage. However, mixed gB genotype infections are associated
      with higher viral loads and delayed viral clearance.

PMID- 19751152
TI  - Vertical transmission of hepatitis B virus (HBV) from mothers negative for HBV
      surface antigen and positive for antibody to HBV core antigen.
AB  - BACKGROUND: Hepatitis B virus (HBV) can be transmitted by blood donors and organ
      donors who are positive for antibody to HBV core antigen (anti-HBc) but negative
      for all other HBV markers. Therefore, we evaluated the risk of infection for
      babies of mothers with this serostatus. METHODS: A total of 2365 HBV surface
      antigen (HBsAg)-negative pregnant women were included in the study and screened
      for anti-HBc. Blood samples for screening were collected 1 day before or after
      delivery. Infants of mothers with positive anti-HBc test results were tested 3-4
      months after birth. RESULTS: Of 2365 mothers, 147 (6.2%) were anti-HBc positive.
      Follow-up tests were performed using samples from 105 children. Samples were
      tested for all HBV markers, including HBV DNA, which was evaluated using a highly
      sensitive polymerase chain reaction assay (Taq PCR). Seven children (6.6%) had
      markers of HBV infection; the Taq PCR detected HBV DNA in 5, and HBsAg was
      detected in the other 2. CONCLUSIONS: This study shows that HBV can be
      transmitted perinatally even in the absence of HBsAg. None of the children
      developed chronic HBV infection. Further studies must determine whether routine
      immunization of infants at the age of 3 months gives enough protection against
      HBV infection or whether screening of pregnant women for HBV should be extended,
      with immunization of their newborns beginning immediately after birth.

PMID- 19751153
TI  - Cost-effectiveness of a potential prophylactic Helicobacter pylori vaccine in the
      United States.
AB  - BACKGROUND: Helicobacter pylori vaccines are under development to prevent
      infection. We quantified the cost-effectiveness of such a vaccine in the United
      States, using a dynamic transmission model. METHODS: We compartmentalized the
      population by age, infection status, and clinical disease state and measured
      effectiveness in quality-adjusted life years (QALYs). We simulated no
      intervention, vaccination of infants, and vaccination of school-age children.
      Variables included costs of vaccine, vaccine administration, and gastric cancer
      treatment (in 2007 US dollars), vaccine efficacy, quality adjustment due to
      gastric cancer, and discount rate. We evaluated possible outcomes for periods of
      10-75 years. RESULTS: H. pylori vaccination of infants would cost $2.9 billion
      over 10 years; savings from cancer prevention would be realized decades later.
      Over a long time horizon (75 years), incremental costs of H. pylori vaccination
      would be $1.8 billion, and incremental QALYs would be 0.5 million, yielding a
      cost-effectiveness ratio of $3871/QALY. With school-age vaccination, the cost
      effectiveness ratio would be $22,137/QALY. With time limited to <40 years, the
      cost-effectiveness ratio exceeded $50,000/QALY. CONCLUSION: When evaluated with a
      time horizon beyond 40 years, the use of a prophylactic H. pylori vaccine was
      cost-effective in the United States, especially with infant vaccination.

PMID- 19751154
TI  - Hyponatremia-induced osteoporosis.
AB  - There is a high prevalence of chronic hyponatremia in the elderly, frequently
      owing to the syndrome of inappropriate antidiuretic hormone secretion (SIADH).
      Recent reports have shown that even mild hyponatremia is associated with impaired
      gait stability and increased falls. An increased risk of falls among elderly
      hyponatremic patients represents a risk factor for fractures, which would be
      further amplified if hyponatremia also contributed metabolically to bone loss. To
      evaluate this possibility, we studied a rat model of SIADH and analyzed data from
      the Third National Health and Nutrition Examination Survey (NHANES III). In rats,
      dual-energy X-ray absorptiometry (DXA) analysis of excised femurs established
      that hyponatremia for 3 months significantly reduced bone mineral density by
      approximately 30% compared with normonatremic control rats. Moreover, micro
      computed tomography (microCT) and histomorphometric analyses indicated that
      hyponatremia markedly reduced both trabecular and cortical bone via increased
      bone resorption and decreased bone formation. Analysis of data from adults in
      NHANES III by linear regression models showed that mild hyponatremia is
      associated with increased odds of osteoporosis (T-score -2.5 or less) at the hip
      [odds ratio (OR) = 2.85; 95% confidence interval (CI) 1.03-7.86; p < .01]; all
      models were adjusted for age, sex, race, body mass index (BMI), physical
      activity, history of diuretic use, history of smoking, and serum 25
      hydroxyvitamin D [25(OH)D] levels. Our results represent the first demonstration
      that chronic hyponatremia causes a substantial reduction of bone mass. Cross
      sectional human data showing that hyponatremia is associated with significantly
      increased odds of osteoporosis are consistent with the experimental data in
      rodents. Our combined results suggest that bone quality should be assessed in all
      patients with chronic hyponatremia.

PMID- 19751155
TI  - Prevention of bloodstream infections by use of daily chlorhexidine baths for
      patients at a long-term acute care hospital.
AB  - OBJECTIVE: To evaluate the effect of bathing patients with 2% chlorhexidine on
      the rates of central vascular catheter (CVC)-associated bloodstream infection
      (BSI) at a long-term acute care hospital (LTACH). DESIGN: Quasi-experimental
      study. SETTING: A 70-bed LTACH in the greater Chicago area. PATIENTS: All
      consecutive patients admitted to the LTACH during the period from February 2006
      to February 2008. METHODS: For patients at the LTACH, daily 2% chlorhexidine
      baths were instituted during the period from September 2006 until May 2007 (ie,
      the intervention period). A preintervention period (in which patients were given
      daily soap-and-water baths) and a postintervention period (in which patients were
      given daily nonmedicated baths and weekly 2% chlorhexidine baths) were also
      observed. The rates of CVC-associated BSI and ventilator-associated pneumonia
      were analyzed for the intervention period and for the pre- and postintervention
      periods. RESULTS: The rates of CVC-associated BSI were 9.5, 3.8, and 6.4 cases
      per 1,000 CVC-days during the preintervention, intervention, and postintervention
      periods, respectively. By the end of the intervention period, there was a net
      reduction of 99% in the CVC-associated BSI rate. No changes were seen in the
      rates of ventilator-associated pneumonia during the preintervention and
      intervention periods. CONCLUSION: Daily chlorhexidine baths appeared to be an
      effective intervention to reduce rates of CVC-associated BSI in an LTACH.

PMID- 19751156
TI  - Proposed checklist of hospital interventions to decrease the incidence of
      healthcare-associated Clostridium difficile infection.
AB  - BACKGROUND: The incidence and severity of Clostridium difficile infection (CDI)
      are increasing, and previously described interventions for controlling the spread
      of CDI are not easily generalized to multiple healthcare institutions. OBJECTIVE:
      We tested prevention and treatment bundles to decrease the incidence of CDI and
      the mortality associated with CDI at our hospital. DESIGN: Observational before
      after study of adult patients admitted to a tertiary care, university-affiliated
      hospital during the period from January 2004 through December 2008. METHODS: In
      January 2006, we launched an educational campaign and introduced a prevention
      bundle-a series of specific processes aimed at preventing the transmission of C.
      difficile among hospitalized patients, including enhanced isolation practices,
      laboratory notification procedures, and steps coordinating infection control and
      environmental services activities. In April 2006, we implemented a treatment
      bundle-a set of hospital-wide treatment practices aimed at minimizing the risk of
      serious CDI complications. We tracked quarterly incidence rates and case-fatality
      rates for healthcare-associated CDI cases at our hospital. Our main outcome was
      the healthcare-associated CDI incidence rate, measured as the number of
      healthcare-associated cases of CDI per 1,000 patient-days. RESULTS: We followed
      patients for a total of 1,047,849 patient-days. The healthcare-associated CDI
      incidence rates fell from an average of 1.10 cases per 1,000 patient-days before
      intervention to 0.66 cases per 1,000 patient-days after intervention. This
      statistically significant decrease amounts to a 40% reduction in incidence after
      the intervention. CONCLUSIONS: Our intervention was successful in reducing the
      incidence of CDI at our hospital. On the basis of our experience, we propose the
      use of a checklist of hospital interventions to decrease the incidence of
      healthcare-associated CDI.

PMID- 19751157
TI  - Comments on study of paw pad lesions in dogs.

PMID- 19751158
TI  - Authorities examining "enhancements" for milk screening.

PMID- 19751159
TI  - Comments on study of paw pad lesions in dogs.

PMID- 19751160
TI  - What is your diagnosis?

PMID- 19751161
TI  - Pathology in practice.

PMID- 19751162
TI  - Revenue, expenses, and returns on resources for US veterinary private practices,
      2005 and 2007.

PMID- 19751163
TI  - Rabies surveillance in the United States during 2008.
AB  - During 2008, 49 states and Puerto Rico reported 6,841 cases of rabies in animals
      and 2 cases in humans to the CDC, representing a 3.1% decrease from the 7,060
      cases in animals and 1 case in a human reported in 2007. Approximately 93% of the
      cases were in wildlife, and 7% were in domestic animals. Relative contributions
      by the major animal groups were as follows: 2,389 (34.9%) raccoons, 1,806 (26.4%)
      bats, 1,589 (23.2%) skunks, 454 (6.6%) foxes, 294 (4.3%) cats, 75 (1.1%) dogs,
      and 59 (0.9%) cattle. Compared with numbers of cases reported in 2007, numbers of
      cases reported in 2008 increased among cats, cattle, and skunks and decreased
      among dogs, raccoons, bats, and foxes. Numbers of rabid raccoons reported during
      2008 decreased in 11 of the 20 eastern states where raccoon rabies was enzootic;
      overall number of rabid raccoons reported decreased by 8.6% during 2008, compared
      with 2007. On a national level, the number of rabies cases involving skunks
      increased by 7.7% during 2008, compared with the number reported in 2007; this
      was the first increase in the number of reported rabid skunks since 2006. The
      total number of cases of rabies reported nationally in foxes decreased 1.7% in
      2008, compared with 2007. The 1,806 cases of rabies reported in bats represented
      a 6.7% decrease, compared with the number reported in 2007. One case of rabies in
      a dog imported from Iraq was reported at a quarantine station in New Jersey
      during 2008. Follow-up of potentially exposed animals in the same shipment did
      not reveal any secondary transmission. The United States remained free from dog
      to-dog transmission of canine rabies virus variants. Total number of rabid dogs
      reported decreased 19.4% in 2008, compared with 2007. Two human rabies cases were
      reported from California and Missouri during 2008. The California case involved a
      recent immigrant from Mexico and was attributed to a newly identified rabies
      virus variant most likely associated with Mexican free-tailed bats. The case in
      Missouri was attributed to a rabies virus variant associated with eastern
      pipistrelle and silver-haired bats.

PMID- 19751164
TI  - Rabies in vaccinated dogs and cats in the United States, 1997-2001.
AB  - OBJECTIVE: To identify cases of rabies involving vaccinated dogs and cats in the
      United States. DESIGN: Retrospective data review. SAMPLE POPULATION: 41 states
      that reported >or= 1 rabid dog or cat between 1997 and 2001. PROCEDURES: States
      were contacted to request information on numbers of dogs and cats tested for
      rabies between 1997 and 2001. For animals with a history of rabies vaccination,
      respondents were asked to provide details of the vaccination history, age,
      history of exposure to rabid animals, time between exposure and onset of clinical
      signs, clinical signs, duration of clinical signs, and whether the animal had
      died or was euthanatized. RESULTS: 21 of the 41 (51%) states agreed to
      participate in the study. A total of 264 rabid dogs and 840 rabid cats were
      identified during the study period. Thirteen (4.9%) rabid dogs and 22 (2.6%)
      rabid cats had a history of rabies vaccination. Of these, 2 dogs and 3 cats were
      classified as currently vaccinated. Overall, 6 animals (1 dog and 5 cats) had a
      history of receiving 2 doses of rabies vaccine in their lifetime, including 2
      cats that were classified as currently vaccinated. CONCLUSIONS AND CLINICAL
      RELEVANCE: Results suggested that rabies is uncommon in vaccinated dogs and cats
      but can occur. Veterinarians should include rabies in the differential diagnosis
      for any dog or cat with clinical signs compatible with rabies regardless of
      vaccination history. Continued surveillance is imperative to document vaccination
      failure and identify trends related to vaccination failure.

PMID- 19751165
TI  - Appreciation for study on bromide administration in dogs.

PMID- 19751166
TI  - Thoughts on studies linking occupational exposures to anesthetic waste gases.

PMID- 19751167
TI  - Randomized, controlled clinical trial of the efficacy of fluoxetine for treatment
      of compulsive disorders in dogs.
AB  - OBJECTIVE: To evaluate efficacy of fluoxetine hydrochloride for treatment of
      compulsive disorders in dogs. DESIGN: Randomized, controlled clinical trial.
      ANIMALS: 63 dogs with compulsive disorders. PROCEDURES: The diagnosis was
      confirmed on the basis of analysis of videotapes of the dogs' behavior by 3
      veterinary behaviorists, results of physical examination and clinicopathologic
      testing, and, when necessary, telephone interviews with owners. Dogs were
      randomly assigned to treatment with fluoxetine (1 to 2 mg/kg [0.45 to 0.9 mg/lb],
      PO, q 24 h) or a placebo. Owners did not receive any advice regarding behavioral
      or environmental modifications. Severity of episodes was measured through
      telephone interviews every 2 weeks and on the basis of a daily diary kept by each
      owner. RESULTS: 42 days after the initiation of treatment, the proportion of dogs
      with a decrease in severity of the compulsive disorder, as reported by the
      owners, was significantly higher for dogs treated with fluoxetine than for
      control dogs, and dogs treated with fluoxetine were significantly more likely
      (odds ratio, 8.7) to have a decrease in severity of the compulsive disorder.
      However, mean number and duration of compulsive episodes, as determined from
      daily diary entries, did not differ significantly between groups. The most common
      adverse effects were decreased appetite and mild lethargy. CONCLUSIONS AND
      CLINICAL RELEVANCE: Results suggested that fluoxetine may be efficacious in the
      treatment of compulsive disorders in dogs, although results were equivocal. The
      present study did not examine whether fluoxetine was more efficacious than or
      synergistic with behavioral and environment modifications.

PMID- 19751168
TI  - Computed tomography-assisted management of a mandibular dentigerous cyst in a dog
      with a nasal carcinoma.
AB  - CASE DESCRIPTION: A 6-year-old neutered male Boston Terrier was examined to
      determine the cause of sneezing, bilateral nasal discharge, nasal congestion,
      lethargy, and coughing of 2 months' duration. CLINICAL FINDINGS: An
      undifferentiated nasal carcinoma was diagnosed. During computed tomography (CT)
      evaluation of response to tomotherapy radiation treatment, a mandibular
      dentigerous cyst, associated with an unerupted left mandibular first premolar,
      was monitored for expansion. TREATMENT AND OUTCOME: The dog had a profound
      response to radiation treatment, and the nasal carcinoma totally resolved. It was
      determined on the basis of CT that the rate of expansion of the dentigerous cyst
      was placing the dog at risk for mandibular fracture and loss of vitality to the
      surrounding teeth. The unerupted left mandibular first premolar and associated
      dentigerous cyst were surgically removed and submitted for histologic evaluation.
      CLINICAL RELEVANCE: Images obtained during sequential CT evaluations performed
      after radiation treatment of nasal carcinoma should be examined for evidence of
      the primary neoplasm as well as to detect unrelated lesions of the orofacial
      region that can compromise the quality of life. Findings of CT evaluations can be
      used to determine when and how to initiate treatment for dentigerous cysts in
      regard to the patient's response to radiation treatment.

PMID- 19751169
TI  - Evaluation of plasma ACTH, alpha-melanocyte-stimulating hormone, and insulin
      concentrations during various photoperiods in clinically normal horses and ponies
      and those with pituitary pars intermedia dysfunction.
AB  - OBJECTIVE: To measure plasma ACTH, alpha-melanocyte-stimulating hormone (aloha
      MSH), and insulin concentrations during various photoperiods between February and
      October in horses and ponies with and without pituitary pars intermedia
      dysfunction (PPID). DESIGN: Cohort study. ANIMALS: 13 clinically normal (control)
      ponies, 14 clinically normal (control) horses, 7 ponies with PPID, and 8 horses
      with PPID. PROCEDURES: Blood samples were collected from February through October
      during 8 photoperiods: 1, February 13 through March 2; 2, April 4 through 6; 3,
      June 19 through 22; 4, August 6 through 7; 5, August 14 through 17; 6, September
      4 through 6; 7, September 26 through 28; and 8, October 16 through 18. Plasma
      ACTH, alpha-MSH, and insulin concentrations at each photoperiod were compared
      among groups. RESULTS: Log ACTH concentration was increased during photoperiod 4
      through 8, compared with photoperiod 1 through 3, in all groups. In photoperiod 3
      through 7, log ACTH concentrations were higher in horses and ponies with PPID,
      compared with values for control horses and ponies. alpha-Melanocyte-stimulating
      hormone (log and raw value) concentration was higher in photoperiod 2 through 8,
      compared with photoperiod 1, in control horses and ponies. In horses and ponies
      with PPID, log alpha-MSH concentration was higher in photoperiod 3 through 8, and
      alpha-MSH concentration was higher in photoperiod 4 through 8, compared with
      photoperiod 1. In control horses and ponies, plasma insulin concentration was
      lower in photoperiod 3 than in photoperiod 1. CONCLUSIONS AND CLINICAL RELEVANCE:
      Plasma alpha-MSH and ACTH concentrations increased as daylight decreased from
      summer solstice (maximum daylight hours) to 12 hours of daylight.

PMID- 19751170
TI  - Multimodal treatment of recurrent sinonasal cryptococcal granulomas in a horse.
AB  - CASE DESCRIPTION: A 7-year-old 509-kg (1,120-lb) Tennessee Walking Horse mare was
      evaluated because of bilateral mucosanguinous nasal discharge, intermittent right
      sided epistaxis, and worsening dyspnea of 9 months' duration. CLINICAL FINDINGS:
      Multiple masses in the nasopharynx were detected via endoscopic and radiographic
      examinations. Cytologic and histologic examinations of biopsy specimens of 1 mass
      revealed round yeasts with thick nonstaining capsules and occasional narrow-based
      budding that resembled cryptococcal organisms. TREATMENT AND OUTCOME: Oral
      administration of fluconazole and organic ethylenediamine dihydriodide and
      intermittent intralesional injections with fluconazole, amphotericin B, and
      formalin resulted in resolution of lesions for a period of 2.5 years. The horse
      then developed exophthalmos, recurring clinical signs, and extensive
      nasopharyngeal masses. The masses were surgically debulked via a large
      frontonasal bone flap, and the horse was treated with IV injections of
      amphotericin B and long-term oral administration of fluconazole. Clinical signs
      did not recur in the following 2-year period. A presumptive diagnosis of
      cryptococcosis was made following cytologic and histologic evaluations of the
      masses; results of serologic analysis and fungal culture confirmed infection with
      Cryptococcus neoformans. CLINICAL RELEVANCE: Cryptococcal infection of the upper
      respiratory tract in horses has previously been described as a uniformly fatal
      disease. As this case report illustrates, medical and surgical treatment of
      sinonasal cryptococcal granulomas in horses may be successful, but the importance
      of long-term follow-up and the potential for disease recrudescence should be
      considered. As efficacious antifungal agents become less expensive, their
      increased use will likely decrease mortality rates in horses with fungal
      infections.

PMID- 19751171
TI  - Partial resection of the plica salpingopharyngeus for the treatment of three
      foals with bilateral tympany of the auditory tube diverticulum (guttural pouch).
AB  - CASE DESCRIPTION: 3 foals were referred for treatment of tympany of the auditory
      tube diverticulum (guttural pouch). CLINICAL FINDINGS: Bilateral guttural pouch
      tympany was diagnosed in all 3 foals on the basis of clinical signs and results
      of radiographic and endoscopic evaluations and gutturocentesis. In each foal,
      previous medical or surgical interventions or both had failed to correct the
      problem. TREATMENT AND OUTCOME: Bilateral surgical resection of the plica
      salpingopharyngeus was performed. Follow-up telephone interviews with owners 8
      months to 3 years after surgery revealed that long-term resolution of the tympany
      had been achieved in each foal, with few to no postsurgical complications.
      CLINICAL RELEVANCE: Surgical correction of refractory bilateral guttural pouch
      tympany can be accomplished by resection of the plica salpingopharyngeus within
      the pharyngeal opening of the Eustachian tube. In the foals of this report,
      permanent resolution of tympany was apparently achieved without interfering with
      upper airway function, providing support for the use of surgical resection of the
      plica salpingopharyngeus in the treatment of bilateral guttural pouch tympany.

PMID- 19751172
TI  - Effect of lameness on sow longevity.
AB  - OBJECTIVE: To analyze the association of lameness and performance variables on
      sow longevity by use of time-to-event analysis. DESIGN: Cohort study. ANIMALS:
      674 sows from a commercial breeding herd. PROCEDURES: A lameness assessment was
      performed on each sow. Data on farrowing performance and longevity were collected
      for the sows during 3 or fewer parities from the database of the herd during 2005
      and 2006. The association of risk factors with sow longevity within 350 days
      after lameness assessment was analyzed via Cox regression analysis. Pigs per day,
      total production days, and survival at 350 days after lameness evaluation were
      compared between lame and nonlame sows. RESULTS: Numbers of preweaning baby pig
      deaths, stillborn pigs, and mummified pigs were negatively associated with sow
      longevity within 350 days after lameness assessment. A higher number of pigs born
      alive and younger parity of sows were protective. Lame sows had a higher risk
      (1.710 times as high) of removal from the herd within 350 days after lameness
      assessment. The number of pigs born alive per day, survival of sows at 350 days,
      and total number of days in the herd were lower in lame sows. CONCLUSIONS AND
      CLINICAL RELEVANCE: Results of this study indicated significant differences in
      the survivability of lame and nonlame sows in a commercial herd. Parity and
      farrowing performance variables were factors influencing sow longevity in this
      herd. Producers need to minimize sow lameness and remove lame sows from a herd
      early (when treatment is not an option) to minimize economic loss.

PMID- 19751173
TI  - Fecal shedding of, antimicrobial resistance in, and serologic response to
      Salmonella Typhimurium in dairy calves.
AB  - OBJECTIVE: To determine the duration of fecal shedding of and serologic response
      to Salmonella spp after natural infection in dairy calves and characterize
      Salmonella organisms recovered from these herds. DESIGN: Longitudinal study.
      ANIMALS: Calves from 2 dairy herds (A and B) in the northeast United States that
      were identified at the beginning of a Salmonella outbreak. PROCEDURES: Fecal
      samples were collected twice per week (herd A) or once per week (herd B); blood
      samples were collected for serologic testing once per week in both herds.
      Bacteriologic culture of fecal samples was performed, and Salmonella isolates
      were characterized by serotype, pulsed-field gel electrophoresis (PFGE) pattern,
      and antimicrobial resistance profile. RESULTS: All Salmonella isolates from herd
      A were serovar Typhimurium var Copenhagen, had the same PFGE pattern, and were
      resistant to at least 9 antimicrobials. All isolates from herd B were Salmonella
      Typhimurium, represented 2 PFGE patterns, and were susceptible to all
      antimicrobials evaluated. The estimated duration of fecal shedding was 14 days in
      herd A and 9 days in herd B. Few calves were seropositive for antibody against
      Salmonella lipopolysaccharide within the first week after birth (0 of 20 in herd
      A and 13 of 79 in herd B) or seroconverted (6 in herd A and 4 in herd B). Fecal
      shedding was more common in calves that seroconverted, but overall, there was not
      a strong association between seropositivity and fecal shedding of Salmonella
      organisms. CONCLUSIONS AND CLINICAL RELEVANCE: Although the herds differed in
      serologic response and Salmonella subtype, the duration of fecal shedding among
      calves was similar between herds.

PMID- 19751174
TI  - Herd-level prevalence of Mycoplasma spp mastitis and characteristics of infected
      dairy herds in Utah as determined by a statewide survey.
AB  - OBJECTIVE: To determine herd-level prevalence of Mycoplasma spp mastitis in Utah
      dairy herds and characterize farms and management practices for positive herds.
      DESIGN: Epidemiologic study. SAMPLE POPULATION: Bulk tank milk samples from 222
      of 285 (78%) dairy farms in Utah. PROCEDURES: Milk haulers or dairy producers
      collected 5 milk samples from all bulk tanks at 3- to 4-day intervals for
      mycoplasmal culture. Owners of all positive herds were offered follow-up visits.
      RESULTS: Milk samples from 16 of 222 (7%) herds had positive mycoplasmal culture
      results. Follow-up information was obtained from 14 of 16 herds; 12 provided
      complete data. Some characteristics of mycoplasma-positive herds included the
      following: 8 of 14 herds had > 750 lactating cows, 9 of 11 had bulk tank milk
      somatic cell count of 140,000 to 240,000 cells/mL, 7 of 11 had actual milk
      production of 9,535 to 11,622 kg (21,000 to 25,600 lb)/305 d, 11 of 12 had cows
      with clinical mastitis that was nonresponsive to treatment and involved >or= 2
      mammary gland quarters, 9 of 12 had cows with clinical mastitis that spread from
      1 mammary gland quarter to another, 8 of 12 had cows with droopy ears, 7 of 12
      had cows with a head tilt, 7 of 12 used common milking towels, 2 of 12 were
      closed to replacement cattle for > 1 year, and 2 of 12 purchased bulls only.
      CONCLUSIONS AND CLINICAL RELEVANCE: Herd-level prevalence of mycoplasma mastitis
      in Utah was relatively high, compared with other areas of the United States.

PMID- 19751175
TI  - More on the prevalence of cardiomyopathy in cats.

PMID- 19751176
TI  - Evaluation of ISCOMs for immunization against hepatitis B.
AB  - Immune stimulating complexes (ISCOMs) incorporating recombinant hepatitis B
      surface antigen (rHBsAg) were prepared for induction of humoral and cellular
      immunity by subcutaneous administration. Prepared ISCOMs were characterized for
      their size, shape, incorporation efficiency, zeta potential, antigen integrity,
      antigen conformation and immunogenicity by biophysical and immunological
      techniques including transmission electron microscopy (TEM), Dynamic light
      scattering (DLS), SDS-PAGE, fluorescence spectroscopy, in vitro potency test and
      in vivo humoral and cellular immune stimulatory efficacy in Balb/c mice. Prepared
      ISCOM particles show characteristic cage like morphology with average size of 44
      approximately nm, polydispersity index 0.1, negative zeta potential (-21.7 mV)
      and antigen association efficiency approximately 39%. Tryptophan emission
      fluorescence and in vitro potency assay data suggest that association of rHBsAg
      with ISCOMs results in local electrostatic interactions, motional restriction of
      tryptophan residues of the protein resulting in reduction of anti-rHBsAg
      monoclonal antibodies binding affinity. Immunization with rHBsAg ISCOMs resulted
      in upregulation of specific cellular (IFN-gamma and IL-2) as well as IgG response
      (IgG2a isotype biased) humoral response in Balb/c mice. Immune responses were
      significantly higher than those produced by of alum-adsorbed antigen (alum
      rHBsAg) after (one booster) (p < 0.001). These data demonstrate that although the
      conformation of rHBsAg after incorporation into ISCOMs was moderately altered but
      due to strong adjuvant ability, rHBsAg ISCOMs were highly immunogenic as compared
      to marketed rHBsAg formulations by subcutaneous route of administration.

PMID- 19751177
TI  - Comparative binding analysis of monoclonal antibodies against native and mutant
      type in ErbB2 receptor: a theoretical modeling approach.
AB  - Trastuzumab and pertuzumab are monoclonal antibodies, used for inhibiting the
      ErbB2 receptor which is over expressed in breast and ovarian cancer. In this
      study, we identified that the most detrimental single point mutation is from
      tryptophan to cysteine at the residue position of 452 on ErbB2 receptor by using
      I-Mutant 2.0, SIFT and PolyPhen programs. The modeled mutant showed less
      stability than native ErbB2 protein based on both total energy of the mutant and
      stabilizing residues in the mutant protein. This is due to deviation between the
      mutant and native ErbB2 having the RMSD of about 2.83A. Further, we found,
      pertuzumab showed a marginal higher binding affinity with ErbB2 receptor of
      native and mutant type with a binding free energy of -16.01 kcal/mole each as
      compared to trastuzumab, showing a binding free energy of -15.26 kcal/mole in
      ErbB2 of native type. On the contrary, trastuzumab showed a remarkably high
      binding affinity with ErbB2 receptor of mutant type having the binding free
      energy -24.40 kcal/mol. Moreover, the reason for high binding efficiency of
      trastuzumab with mutant ErbB2 is due to additional hydrogen bonding of amino acid
      Asn30 of trastuzumab with Asp596 and Glu598 of ErbB2 receptor of mutant type.
      Based on this work, we propose that pertuzumab could be the potential monoclonal
      antibody against ErbB2 for native type and trastuzumab could be the potential
      monoclonal antibody against ErbB2 of mutant type. Therefore combined
      administration of trastuzumab and pertuzumab could be a novel strategy for breast
      cancer treatment.

PMID- 19751178
TI  - Efficient production of gossypol from hairy root cultures of cotton (Gossypium
      hirsutum L.).
AB  - A protocol for induction and establishment of Agrobacterium rhizogenes mediated
      hairy root culture of Gossypium hirsutum was developed through infection with the
      A4 strain and co-cultivation on hormone-free semi-solid MS medium with B5
      vitamins. It resulted in the emergence of hairy roots from the leaf explants, 21
      days after infection. The transformation of hairy roots was established by PCR
      amplification of rol B and rol C genes of the Ri plasmid. All root lines
      expressed gossypol, although distinct inter-clonal quantitative variations were
      noticed. Five independent hairy root lines were studied for their growth kinetics
      as well as gossypol production. The yield potentials of one of them superseded
      others, as well as the non-transformed, in-vitro grown control roots. The content
      of gossypol in hairy roots reached a level of 2.43 mg/g DW. It was 4.5 times
      higher than in vitro and 1.47 times higher than in vivo grown roots of G.
      hirsutum. Selection of high gossypol producing hairy root lines of G. hirsutum
      can provide an alternative source for large-scale production of gossypol.

PMID- 19751179
TI  - Clinical applications of creatine supplementation on paediatrics.
AB  - Creatine plays a central role in energy metabolism and is synthesized in the
      liver, kidney and pancreas. In healthy patients, it is transported via the blood
      stream to the muscles, heart and brain with high and fluctuating energy demands
      by the molecule creatine transporter. Creatine, although naturally synthesized in
      the human body, can be ingested in the form of supplements and is commonly used
      by athletes. The purpose of this review was to assess the clinical applications
      of creatine supplementation on paediatrics. Creatine metabolism disorders have so
      far been described at the level of two synthetic steps, guanidinoacetate N
      methyltransferase (GAMT) and arginine: glycine amidinotransferase (AGAT), and at
      the level of the creatine transporter 1(CrT1). GAMT and AGAT deficiency respond
      positively to substitutive treatment with creatine monohydrate whereas in CrT1
      defect, it is not able to replenish creatine in the brain with oral creatine
      supplementation. There are also data concerning the short and long-term
      therapeutic benefit of creatine supplementation in children and adults with
      gyrate atrophy (a result of the inborn error of metabolism with ornithine delta-
      aminotransferase activity), muscular dystrophy (facioscapulohumeral dystrophy,
      Becker dystrophy, Duchenne dystrophy and sarcoglycan deficient limb girdle
      muscular dystrophy), McArdle's disease, Huntington's disease and mitochondria
      related diseases. Hypoxia and energy related brain pathologies (brain trauma,
      cerebral ischemia, prematurity) might benefit from Cr supplementation. This
      review covers also the basics of creatine metabolism and proposed mechanisms of
      action.

PMID- 19751180
TI  - Momordica balsamina: a medicinal and neutraceutical plant for health care
      management.
AB  - Momordica balsamina, African pumpkin (Cucurbitaceae), is a tendril-bearing, wild
      climber containing wide spectrum of medicinal and nutritional values and has been
      used as a traditional folk medicine in many countries. The leaves, fruits, seeds,
      and bark of the plant contains resins, alkaloids, flavonoids, glycosides,
      steroids, terpenes, cardiac glycoside, saponins having various medicinal
      importance viz. anti-HIV, anti-plasmodial, shigellocidal, anti-diarrheal, anti
      septic, anti-bacterial, anti-viral, anti-inflammatory, anti-microbial,
      hypoglycemic, antioxidant, analgesic and hepatoprotective properties. The
      therapeutic agent 'Momordin' is capable of inhibiting the growth of HIV and other
      viruses. The leaves are also important source of nutrients having 17 amino acids
      with adequate mineral composition like potassium, magnesium, phosphorus, calcium,
      sodium, zinc, manganese and iron. It also helps to combat the problem of
      micronutrient deficiencies in soil and high value of protein and fat with low
      fibre content. High potassium content is a good source for the management of
      hypertension and other cardiovascular conditions. This plant is being promoted as
      a protein supplement for cereal-based diets in poor rural communities. The
      commercial exploitation of this plant for biopharmaceuticals and neutraceuticals
      are some of the prospective future potential of this wild herb. This review
      discusses the potential of medicinal and nutritional importance of this wild herb
      for health care management.

PMID- 19751181
TI  - Chlorophytum borivilianum: a white gold for biopharmaceuticals and
      neutraceuticals.
AB  - Chlorophytum borivilianum Santapau & Fernandes (Liliaceae) also known as 'Safed
      Musli' is a traditional rare Indian medicinal herb which has many therapeutic
      applications in Ayurvedic, Unani, Homeopathic and Allopathic system of medicine.
      Its roots (tubers) are widely used for various therapeutic applications. It is
      used to cure physical illness and weakness, as an aphrodisiac agent and
      revitalizer, as general sex tonic, remedy for diabetes, arthritis and increasing
      body immunity, curative for natal and postnatal problems, for rheumatism and
      joint pains, increase lactation in feeding mothers, as antimicrobial, anti
      inflammatory, antitumor agent, also used in diarrhea, dysentery, gonorrhea,
      leucorrhea etc. It has spermatogenic property and is found useful in curing
      impotency, now it is considered as an alternative 'Viagra'. Its root contains
      steroidal and triterpenoidal saponins, sapogenins and fructans which act as
      therapeutic agents and play vital role in many therapeutic applications. It is a
      rich source of over 25 alkaloids, vitamins, proteins, carbohydrates, steroids,
      saponins, potassium, calcium, magnesium, phenol, resins, mucilage, and
      polysaccharides and also contains high quantity of simple sugars, mainly sucrose,
      glucose, fructose, galactose, mannose and xylose. The commercial exploitation of
      this plant and their secondary metabolites, germplasm conservation and in vitro
      production of secondary metabolites for quality control are some of the major
      prospects of this rare medicinal herb. The focus of the present review is to
      galvanize the potential of therapeutic and nutritive values of this herb and
      production of their secondary metabolites. The in vitro tuber induction,
      extraction, purification and characterization of saponins are also discussed in
      the present review.

PMID- 19751182
TI  - Complications of infective endocarditis.
AB  - Infective endocarditis (IE) is a lethal disease if not promptly treated with
      antibiotics, either in association with surgery or not. The incidence of disease
      has not decreased over the last decades due to the change of risk conditions.
      Complications of IE may involve cardiac structures when the infection spreads
      within the heart, or extra cardiac ones when the cause is usually from embolic
      origin; they may also be due to medical treatment or to the septic condition
      itself. A variety of complications may occur in most of patients. The literature
      reports one complication of IE in 57%, two in 26% and three or more in about 14%
      of patients examined. The frequency of specific complications depends on
      variables as the infecting pathogen, duration of disease before therapy and type
      of treatment. However it is often difficult to assess the true incidence of
      complications because the published reviews in literature are frequently based on
      retrospective chart reviews and different diagnostic criteria are used. The
      decision over either indication or timing of surgery should be individualized and
      based on a multidisciplinary approach involving at least cardiologists and
      cardiac surgeons. Congestive heart failure (CHF) is the most important
      complication of IE, which has the greatest impact on prognosis. Periannular
      abscesses are a relatively common complication of IE (42% to 85% of cases during
      surgery or at autopsy respectively), associated with a higher morbidity and
      mortality. Systemic embolization occurs in 22% to 50% of cases; emboli may
      involve major arteries, mostly affecting the central nervous system, but also
      other organs. Splenic abscess is a rare complication of IE, due to direct seeding
      of spleen by an embolus or bacterial seeding of a bland infarction. Neurological
      complications develop in 20% to 40% of patients with IE and represent a dangerous
      subset of complications. Mycotic aneurysms are rare, resulting from diffusion of
      infection to the vessel wall. Actually the clinical profile, the best treatment
      (medical or surgical approach) and outcome of complicated IE are not well
      defined. Changing trends in aetiology of IE with emerging infections from
      Staphylococci, bacteria of the HACEK group and Fungi have resulted in an
      increased frequency of culture negative IE. Sepsis or persistent fever despite
      appropriate antimicrobial therapy, recurrent emboli, heart failure or new
      pathologic murmurs suggest haemodynamic impairment and/or infection extending
      beyond the valve leaflet or prosthetic valvular annulus. The course of the
      disease will consequently get worse with an increasing need of surgery. Patients
      who develop abscesses are more likely to undergo surgery than those who do not
      (84-91% vs 36%), and also their in-hospital mortality rate is higher (19% vs
      11%). A prompt detection of complications often allows an earlier surgical
      treatment which represents the best way to improve the outcome. The introduction
      of molecular methods techniques has increased the ability to identify the causal
      agents of IE, mostly in cases of culture negative endocarditis. Echocardiography,
      mainly from transesophageal (TEE) approach, has significantly improved the
      evaluation of IE allowing to detect the specific signs of the disease as
      vegetations, abscesses, valve insufficiency, prosthetic valve dehiscence,
      fistulas. In our 3rd referral Hospital (Lancisi Heart Hospital, Ancona, Italy) we
      performed a follow-up (mean 8.26 years) of 15 patients with periannular
      complications associated with IE. The long term follow-up showed low mortality
      rate, high incidence of reintervention, improved New York Heart Association
      (NYHA) class in survivors and no changes of the lesions at the echocardiographic
      examination, suggesting that periannular complications have not significantly
      influenced the overall survival in our patients at the follow-up.

PMID- 19751183
TI  - Prevention of bacterial endocarditis.
AB  - Infective endocarditis (IE) is a rare but severe disease with high mortality, and
      results most often from the combination of bacteraemia and a predisposing cardiac
      condition. American Heart Association (AHA) and other national and international
      organizations have made recommendations for the prevention of IE, although no
      randomised clinical trial has confirmed its efficacy. The current tendencies of
      IE prophylaxis, based on 2007 AHA guidelines and recent medical bibliography are
      presented in our review.

PMID- 19751184
TI  - Odontogenic infections in the etiology of infective endocarditis.
AB  - Revised guidelines for the prevention of infective endocarditis published by the
      American Heart Association in 2007 do not support the indiscriminate use of
      antibiotic prophylaxis for dental procedures. However, they still recommend the
      use of prophylaxis for high-risk patients before dental treatments likely to
      cause bleeding. Given the high prevalence of bacteremia of dental origin due to
      tooth-brushing, mastication or other daily activities, it appears unlikely that
      infective endocarditis from oral microorganisms can be completely prevented. A
      good oral health status and satisfactory level of oral hygiene are sufficient to
      control the consequences of the systemic spread of oral microorganisms in healthy
      individuals. However, caution is still needed and prophylactic antibiotics must
      be administered to susceptible or medically compromised patients. This review
      briefly outlines the current concepts of odontogenic bacteraemia and antibiotic
      prophylaxis for patients undergoing dental treatment.

PMID- 19751185
TI  - Prosthetic valve endocarditis: diagnostic approach and treatment options.
AB  - Prosthetic valve endocarditis (PVE) is a grave medical entity with potentially
      fatal end results. The disease encompasses a rather small but, in the same time,
      vital part of IE incidents that is probable to be augmented in future years. PVE
      occurs in 1-4% of valve recipients during the first year following valve
      replacement, and in approximately 1 % per year afterwards. The type of prosthetic
      valve (mechanical versus bioprosthetic) seems not having an impact on the rate of
      development of IE and it is comparable in both groups (0.8 cases per year of
      follow-up). The pathogenetic mechanisms, pathogens implicated, clinical features
      and diagnostic approach of PVE will be reviewed here, along with the
      antibacterial and potential surgical treatment and prevention of the disease.

PMID- 19751186
TI  - Update on the treatments of non-alcoholic fatty liver disease (NAFLD).
AB  - Non-alcoholic fatty liver disease (NAFLD) is the most frequent cause of liver
      damage and alteration of hepatic enzymes. NAFLD is strongly associated with
      metabolic syndrome and obesity. It is characterized by fat accumulation in the
      liver that may progress throughout hepatic steatosis and inflammation (non
      alcoholic steatohepatitis [NASH]) toward cirrhosis and liver failure. In the last
      decade several studies suggested that NAFLD is an independent cardiovascular risk
      factor that increases cardiovascular mortality. At present, several studies
      investigating possible therapeutic approaches are ongoing. The present review is
      focused on the current and promising treatments of NAFLD.

PMID- 19751187
TI  - A systems biology consideration of the vasculopathy of sickle cell anemia: the
      need for multi-modality chemo-prophylaxsis.
AB  - Much of the morbidity and mortality of sickle cell anemia is accounted for by a
      chronic vasculopathy syndrome. There is currently no identified therapy,
      interventional or prophylactic, for this problem. For two reasons, development of
      an effective therapeutic approach will require a systems biology level
      perspective on the vascular pathobiology of sickle disease. In the first place,
      multiple biological processes contribute to the pathogenesis of vasculopathy: red
      cell sickling, inflammation and adhesion biology, coagulation activation, stasis,
      deficient bioavailability and excessive consumption of NO, excessive oxidation,
      and reperfusion injury physiology. The probable hierarchy of involvement of these
      disparate sub-biologies places inflammation caused by reperfusion injury
      physiology as the likely, proximate, linking pathophysiological factor. In the
      second place, most of these sub-biologies overlap with each other and, in any
      case, have multiple points of potential interaction and transactivation.
      Consequently, an approach modeled upon chemotherapy for cancer is needed. This
      would be a truly multi-modality approach that hopefully could be achieved via
      employment of relatively few drugs. It is proposed here that the specific
      combination of a statin with suberoylanilide hydroxamic acid would provide a
      suitable, broad, multi-modality approach to chemo-prophylaxis for sickle
      vasculopathy.

PMID- 19751190
TI  - Transcriptional mechanisms by the coregulator MAML1.
AB  - The Mastermind-like (MAML) proteins are transcriptional coactivators for Notch
      signaling, an evolutionarily conserved pathway that plays several key roles in
      development and in human disease. The MAML family contains MAML1, MAML2, and
      MAML3. More recently, MAML1 has been shown to function as a coactivator for the
      tumor suppressor p53, the MADS box transcription enhancer factor (MEF) 2C, and
      beta-catenin. In addition, MAML1 has been reported to interact with the histone
      acetyltransferase p300, and this interaction increases p300 activity.
      Furthermore, MAML1 binds to CDK8, which is a subunit of the Mediator complex. The
      function of MAML1 as a coactivator for diverse activators, and MAML1 interaction
      with broadly used coactivators, suggests that MAML1 might be a key molecule that
      connects various signaling pathways to regulate cellular processes in normal
      cells and in human disease.

PMID- 19751189
TI  - Theoretical considerations on the topological organization of receptor mosaics.
AB  - The concept of Receptor Mosaic (RM) is discussed; hence the integrative functions
      of the assemblage of G-protein coupled receptors physically interacting in the
      plane of the plasma membrane. The main focus is on a hetero-trimer of G-protein
      coupled receptors, namely the A2A-D2-CB1 receptor trimer. A bioinformatics
      analysis was carried out on the amino acid sequence of these receptors to
      indicate domains possibly involved in the receptor-receptor interactions. Such a
      bioinformatic analysis was also carried out on the RM formed by mGLU R5, D2 and
      A2A. The importance of topology, i.e., of the reciprocal localisation of the
      three interacting receptors in the plan of the membrane for the RM integrative
      functions is underlined. However, it is also pointed out that this fundamental
      aspect still waits techniques capable of an appropriate investigation. Finally,
      it is discussed how RM topology can give hints for a structural definition of the
      concept of hub receptor. Thus, just as in any network, the receptor operating as
      a hub is the one that in the molecular network formed by the receptors has the
      highest number of inputs.

PMID- 19751191
TI  - Genetic variants of alpha1-antitrypsin.
AB  - Alpha1-antitrypsin (alpha1-AT) is a 52 kDa sialoglycoprotein. The function of
      alpha1-antitrypsin is to protect the lower respiratory tract of lungs from
      proteolytic degradation by neutrophil elastase. Severe genetic deficiency of
      alpha1-AT is associated with early onset emphysema and liver diseases. alpha1-AT
      also exhibits anti-inflammatory activities independent of its protease inhibitor
      function. There are over 90 genetic variants of human alpha1-antitrypsin. These
      variants occur due to amino acid substitution / deletion which results in charge
      differences. Based on charge differences these variants have been identified by
      isoelectric focusing. The two most common deficiency variants are S and Z. The S
      variant migrates anodal to Z variant. The Z variant migrates most cathodal in
      isoelectric focusing, hence named Z. In Z variant, the beta-sheet A undergoes
      expansion, therefore it can easily accept the reactive site loop of a second
      alpha1-AT molecule and consequently form polymers of alpha1-AT. These polymers of
      alpha1-AT aggregate in the hepatocytes and show liver and lungs diseases.
      Contrary to this, the S variant of alpha1-AT is not associated with any
      significant clinical disease because the conformation of the inhibitor is not
      altered significantly. The Z related pathologies could be treated by liver
      transplantation, augmentation therapy, gene therapy, peptide therapy and chemical
      chaperone therapy. In addition to common deficiency variants, there are several
      rare deficiency variants of alpha1-AT like Siiyama, Mmalton, Mprocida, Mheerlen,
      Mmineral springs, Mnichinan, Pduarte, Wbethesda Zaugsberg, and Zbristol. In
      Siiyama, Mmalton, Mnichinan and Zaugsberg, the beta-sheet A is present in an open
      state therefore these variants readily undergo polymerization and consequently
      show aggregation in the hepatocytes. In Mprocida, Mheerlen, Mmineral springs,
      Pduarte and Wbethesda the conformation is altered significantly therefore these
      variants become conformationally less stable and thereby undergo intracellular
      proteolysis. These rare genetic variants show lungs and / or liver disease. There
      are several null variants of alpha1-AT that are not detected either at the stage
      of transcription or translation. The examples of some of the null variants are
      QOcardiff, QOhong kong, QOgranite falls, QObellingham, QOmattawa, QObolton, and
      QOludwigshafen. The molecular basis of deficiency of these variants also forms
      the theme of this review.

PMID- 19751192
TI  - Anionic antimicrobial peptides from eukaryotic organisms.
AB  - Anionic antimicrobial peptides / proteins (AAMPs) were first reported in the
      early 1980s and since then, have been established as an important part of the
      innate immune systems of vertebrates, invertebrates and plants. These peptides
      are active against bacteria, fungi, viruses and pests such as insects. AAMPs may
      be induced or expressed constitutively and in some cases, antimicrobial activity
      appears to be a secondary role for these peptides with other biological
      activities constituting their primary role. Structural characterization shows
      AAMPs to generally range in net charge from -1 to -7 and in length from 5
      residues to circa 70 residues and for a number of these peptides, post
      translational modifications are essential for antimicrobial activity. Membrane
      interaction appears key to the antimicrobial function of AAMPs and to facilitate
      these interactions, these peptides generally adopt amphiphilic structures. These
      architectures vary from the alpha-helical peptides of some amphibians to the
      cyclic cystine knot structures observed in some plant proteins. Some AAMPs appear
      to use metal ions to form cationic salt bridges with negatively charged
      components of microbial membranes, thereby facilitating interaction with their
      target organisms, but in many cases, the mechanisms underlying the antimicrobial
      action of these peptides are unclear or have not been elucidated. Here, we
      present an overview on current research into AAMPs, which suggests that these
      peptides are an untapped source of putative antimicrobial agents with novel
      mechanisms of action and possess potential for application in the medical and
      biotechnological arenas.

PMID- 19751193
TI  - Leptin, ciliary neurotrophic factor, leukemia inhibitory factor and interleukin
      6: class-I cytokines involved in the neuroendocrine regulation of the
      reproductive function.
AB  - Class-I cytokines represent a large group of molecules involved in different
      physiological processes including host defence, immune regulation, food intake,
      energy metabolism and, relevant for this review, reproduction. In this latter
      respect, here, we focus the attention on four of these molecules, specifically
      leptin, ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF) and
      interleukin-6 (IL-6). These cytokines present similar three-dimensional fold
      structure, interact with related class-I receptors, which are expressed in the
      same regions (i.e., hypothalamus), and activate similar intracellular pathways.
      Leptin and CNTF share functional similarities, by acting at hypothalamic and
      pituitary levels, and their receptors are colocalized in the arcuate and
      paraventricular nuclei of the hypothalamus. For both these molecules, no effect
      on GnRH migration has been described. LIF has also been shown to affect
      gonadotropin secretion and here we present the novel observation that it is also
      able to stimulate GnRH secretion in vitro. Moreover, in the mouse, LIF is
      prenatally expressed in nasal regions where GnRH neurons originate and start
      their migration, and in vitro it stimulates intrinsic cell motility and
      directional migration. The role of the prototypical cytokine, IL-6, on the GnRH
      LH axis is not fully clear and additional information seem necessary to better
      clarify this aspect. In conclusion, the data here discussed suggest that this
      family of cytokines appears to participate to the complex control of the
      reproductive function by affecting the development and function of the
      hypothalamus-pituitary system at different ontogenic times and anatomical sites.

PMID- 19751194
TI  - The many faces of platelet glycoprotein Ibalpha--thrombin interaction.
AB  - The platelet glycoprotein receptor regulates the adhesion of blood platelets to
      damaged blood vessel walls and the subsequent platelet aggregation. One of the
      subunits, platelet glycoprotein Ibalpha (GpIbalpha), binds thrombin, a serine
      protease with both procoagulant and anticoagulant activities. Two groups reported
      the crystal structures of the complex between thrombin and the N-terminal
      extracellular domain (leucine-rich repeat [LRR] domain) of GpIbalpha. In both
      these structures, GpIbalpha was reported to bind two thrombin molecules, but both
      the primary and secondary thrombin binding sites differed between them. We
      performed a detailed comparison of the two structures to look for insights that
      may explain the differences. Our results show that the 1:1 GpIbalpha-thrombin
      complex detected in solution between the crystallized proteins is likely the only
      strong interaction. The anionic sequence (residues 268-284) of GpIbalpha is
      likely responsible for the initial interaction with thrombin and the interaction
      with the rest of LRR domain of GpIbalpha occurs subsequently and may alternate
      between two or more different binding modes. Our modelling suggests the
      interaction between GpIbalpha and thrombin is highly pH-dependent and a small
      change in pH is likely to contribute to the formation of alternate binding modes.
      The differences in the crystal structures reported for the GpIbalpha-thrombin
      complex suggest a fascinating plasticity in this protein-protein interaction that
      may be biologically significant.

PMID- 19751195
TI  - Focus on phosphoarginine and phospholysine.
AB  - Protein phosphorylation is a common signaling mechanism in both prokaryotic and
      eukaryotic organisms. Whilst serine, threonine and tyrosine phosphorylation
      dominate much of the literature there are several other amino acids that are
      phosphorylated in a variety of organisms. Two of these phosphoamino acids are
      phosphoarginine and phospholysine. This review will focus on the chemistry and
      biochemistry of both phosphoarginine and phospholysine. In particular we focus on
      the biological aspects of phosphoarginine as a means of storing and using
      metabolic energy (in place of phosphocreatine in invertebrates), the chemistry
      behind its synthesis and we examine the chemistry behind its highenergy
      phosphoramidate bond. In addition we will be reporting on the incidence of
      phosphoarginine in mammalian cells. Similarly we will be reviewing the current
      findings on the biology and the chemistry of phospholysine and its involvement in
      a variety of biological systems.

PMID- 19751196
TI  - Interleukin-24: a molecule with potential anti-cancer activity and a cytokine in
      search of a function.
AB  - The gene encoding Melanoma-differentiation antigen-7 (MDA-7) was discovered more
      than 10 years ago. Its potential anti-cancer activity was surmised because its
      expression is inversely correlated with the cell proliferation status. Indeed
      adenoviral delivery of this gene proved to be efficient in killing several cancer
      cell lines and great strides have been made concerning its molecular ways of
      action. Later it was shown that mda7 encoded a secreted cytokine which belongs to
      the IL-10, class-II family of cytokines. We recently found that this molecule
      exerted apoptotic activity on stimulating but not on resting lymphocytes from a B
      cell leukaemia. This activity is distinct from that of intracellular MDA-7, and
      may pave the way for using the cytokine in cancers provided that they express the
      IL-24 Receptors; in this respect, melanomas are insensitive to the recombinant
      cytokine due to the lack of IL-24 receptors at their surface. In contrast to its
      anti-cancer activity, the immunological role of IL-24 is still unclear, with
      differences between mice and human. If however it is demonstrated that IL-24 can
      inhibit the function of STAT3 in normal lymphocytes as it is the case in leukemic
      cells, and given that STAT3 is needed for the differentiation of several
      lymphocyte subsets, this will give us hints as to the potential role of this
      cytokine in the immune system.

PMID- 19751197
TI  - A review on mouth dissolving films.
AB  - The ultimate goal of any drug delivery system is the successful delivery of the
      drug to the body; however, patient compliance must not be overlooked. Fast
      dissolving drug delivery systems, such as, Mouth Dissolving Films (MDF), offer a
      convenient way of dosing medications, not only to special population groups with
      swallowing difficulties such as children and the elderly, but also to the general
      population. MDF are the novel dosage forms that disintegrate and dissolve within
      the oral cavity. Intra-oral absorption permits rapid onset of action and helps by
      pass first-pass effects, thereby reducing the unit dose required to produce
      desired therapeutic effect. The present review provides an overview of various
      polymers that can be employed in the manufacture of MDF and highlights the effect
      of polymers and plasticizers on various physico-mechanical properties of MDF. It
      further gives a brief account of formulation of MDF and problems faced during its
      manufacture.

PMID- 19751198
TI  - Gastroretentive drug delivery systems: current developments in novel system
      design and evaluation.
AB  - The task of achieving efficient delivery of drugs that have poor bioavailability
      or narrow absorption windows have plagued the pharmaceutically industry for
      decades. Thus, much research has been dedicated to the development of novel
      polymeric-based gastroretentive drug delivery technologies that may optimize the
      bioavailability and subsequent therapeutic efficacy of such drugs. An effective
      approach of achieving this is through the prolongation of the gastric residence
      time employing several gastroretentive drug delivery mechanisms such as the use
      of buoyant systems, high density systems, magnetic systems, mucoadhesive systems,
      swelling/expanding systems, superporous hydrogels and the inclusion of gastric
      motility retarding agents with biocompatible polymeric materials. It is known
      that variations in the gastric physiology such as, gastric pH, and motility
      exhibit both intra-as well as inter-subject variability demonstrating a
      significant impact on the gastric retention time and drug delivery behavior.
      Nevertheless, gastroretentive drug delivery systems have shown promising results.
      Therefore, in this mini-review, current research and development in this field
      (i.e. over the last 3-5 years), the polymeric material used for the design of
      gastroretentive drug delivery systems and techniques employed for the
      pharmaceutical evaluation of gastroretentive technologies are comprehensively
      revealed and discussed in an assimilatory manner.

PMID- 19751199
TI  - Passive and iontophoretic permeation of glipizide gel: an in vitro and in vivo
      study.
AB  - The purpose of the present work was to formulate and evaluate skin permeability
      of a glipizide gel to assess its suitability for transdermal delivery. A polymer
      gel was prepared by soaking hydroxypropyl methyl cellulose (5 g) overnight in
      phosphate buffer: ethanol (50:50, v/v) and mixing it with separately prepared
      glipizide solution in the same vehicle to bring the concentration to 2 mg /ml. In
      vitro skin permeability was assessed in full thickness skin of rabbits and pigs.
      For in vivo studies New Zealand rabbits were used. In vitro passive permeation
      was carried out in Franz diffusion cell but for iontophoresis, diffusion cell was
      modified according to Glikfield design. Iontophoresis was performed at a current
      density of 0.5 mA/cm2 via silver/silver chloride electrodes with the passive
      controls but for in vivo study current density was reduced to 0.125 mA/cm2. Blood
      samples were analyzed for drug content by HPLC and blood sugar levels were also
      recorded periodically during in vivo permeation. Results of the in vitro study
      indicated that iontophoresis considerably increased the permeation rate of
      glipizide compared to passive controls in both the skin types (P<0.05). For in
      vivo studies current densities and drug concentration had to be lowered to 0.125
      mA/cm2 as excessive permeation resulting in hypoglycemic shocks were noted when
      study was carried out at a current density of 0.5 mA/cm2. The low intensity
      current was well tolerated. The plasma concentration of glipizide was
      significantly higher (P<0.05) than that obtained in the passive controls. The
      study indicated even at very low current density, iontophoresis could enhance the
      permeation of glipizide significantly.

PMID- 19751200
TI  - Preparation and evaluation of gastroretentive floating tablets of acyclovir.
AB  - The present study performed by preparation and evaluation of floating tablets of
      Acyclovir as model drug for prolongation of gastric residence time. Floating
      effervescent tablets were formulated by various materials like hydroxypropyl
      methylcellulose K 4M, K 15M, psyllium husk, swelling agent as crospovidone and
      microcrystalline cellulose and gas generating agent like sodium bicarbonate and
      citric acid and evaluated for floating properties, swelling characteristics and
      in vitro drug release studies. Floating noneffervescent tablets were prepared by
      polypropylene foam powder and different matrix forming polymers like HPMC K 4M,
      Carbopol 934P, xanthan gum and sodium alginate. In vitro drug release studies
      were performed and drug release kinetics evaluated using the linear regression
      method was found to follow both the Higuchi and the Korsmeyer and Peppas
      equation. The drug release mechanism was found fickian type in most of the
      formulations.

PMID- 19751201
TI  - Effectiveness of various drug carriers in controlled release formulations of
      raloxifene HCl prepared by melt mixing.
AB  - In the present study solid dispersions of Raloxifene HCl were prepared by melt
      mixing. As drug carriers, biodegradable/biocompatible aliphatic polyesters were
      used. These formulations were compared to those based on extensively used drug
      carriers such as PEG and Gelucire 50/13. The used aliphatic polyesters namely
      poly(propylene succinate) (PPSu) and poly(propylene adipate) (PPAd) were prepared
      by melt polycondensation. The polyesters have melting points close to human body
      temperature and were used for first time as drug carries. Polymer
      cytocompatibility based on HUVEC cells viability in the presence of increasing
      concentrations of polymer was investigated and it was found that PPSu and PPAd
      exhibit comparable cytocompatibility with poly(dl-lactide). The physical state of
      solid dispersions was evaluated by FTIR, SEM and XRD techniques. In all cases the
      interactions between drug and carriers are limited and thus the dispersed drug
      was mainly in the crystalline state. SEM revealed that the particles size of the
      dispersed drug increases with increasing the drug amount. The release behavior of
      the drug is affected from both the drug amount and the kind of the used carrier.
      The drug is released almost immediately from PEG formulations while Gelucire
      results in sustained release. In formulations that polyesters were used as drug
      carriers the release is slower.

PMID- 19751202
TI  - In-situ formation of liposome of rifampicin: better availability for better
      treatment.
AB  - This study aimed at the preparation and characterization of preformed and in-situ
      formed liposomes for controlled delivery to the lungs. Two different liposome
      formulations were prepared and subjected to characterization of physical
      parameters (vesicle size, appearance, discharge rate, spray pattern and internal
      pressure) and drug release profile (% cumulative drug release and % drug
      retained). Formulations were then subjected to accelerated stability studies as
      per ICH guidelines. It was observed that vesicle size ranged between 2.35 +/-
      0.23 - 2.41+/- 0.3 microm and 1.22 +/- 0.22- 1.34 +/- 0.15 microm respectively
      for preformed and in-situ formed liposomes. The discharge rate and spray area
      were in ranges of 110 +/- 2.4 -123 +/- 2.6 & 115+/- 2.4 -127+/-2.3 mg/ actuation
      & 12.5 +/-1.7 -14.1+/- 2.2 and 13.9 +/- 2.1- 14.7+/- 2.0 cm(2) respectively. In
      situ liposomes showed better controlled release profile then preformed liposomes
      as it released 76.5+/- 2.4 - 58.5 +/- 1.8 % drug in 12 hour while retaining 23.5
      +/- 1.9- 41.5 +/- 1.6 % drug whereas preformed liposomes showed cumulative
      release of 66.5 +/- 2.2- 84.5 +/- 2.3 % and 15.5 +/- 2.4- 33.5+/- 2.1 % fraction
      retained. Upon subjection to accelerated conditions for a period of 60 days,
      preformed liposome completely lost the objective of being controlled release
      formulation as they showed 92+/- 2.4 % cumulative release and only 08 +/- 1.6 %
      fraction retained whereas in-situ formulation showed 62 +/- 2.3 % cumulative
      release and 38 +/- 2.1 % fraction retained.

PMID- 19751203
TI  - Current and future therapeutic strategies for Parkinson's disease.
AB  - The heterogeneity of symptoms and disease progression observed in
      synucleinopathies, of which Parkinson's disease (PD) is the most common
      representative, poses large problems for its treatment and for the discovery of
      novel therapeutics. The molecular basis for pathology is currently unclear, both
      in familial and in sporadic cases. While the therapeutic effects of L-DOPA and
      dopamine receptor agonists are still the gold standards for symptomatic treatment
      in PD, the development of neuroprotective and/or neurorestorative treatments for
      these disorders faces significant challenges due to the poor knowledge of the
      putative targets involved. Recent experimental evidence strongly suggests a
      central role for neurotoxic alpha-synuclein oligomeric species in
      neurodegeneration. The events leading to protein oligomerization, as well as the
      oligomeric species themselves, are likely amenable to modulation by small
      molecules, which are beginning to emerge in high throughput compound screens in a
      variety of model organisms. The therapeutic potential of small molecule
      modulators of oligomer formation demands further exploration and validation in
      cellular and animal disease models in order to accelerate human drug development.

PMID- 19751204
TI  - Kinase inhibitors as potential therapeutics for acute and chronic
      neurodegenerative conditions.
AB  - Kinases, which number > 500 in humans, are a class of enzymes that participate in
      an array of important functions within normal cellular physiology and during
      various pathological conditions. Due to the key role of kinases in the regulation
      of all aspects of cellular signaling and the well established contribution of
      kinase dysregulation to the etiology of many human pathologies, the development
      of kinase inhibitors has emerged as a therapeutic strategy for the treatment of
      human disease, including most notably oncology. Difficulties generating selective
      inhibitors have hampered their use in other therapeutic areas with less tolerance
      for off-target effects. However, with an increasing understanding of kinase
      structures and with the advent of newer inhibitor design strategies more highly
      selective inhibitors are beginning to emerge. This has prompted interest in
      utilizing kinase inhibitors in therapeutic areas beyond oncology, including acute
      and chronic neurodegenerative conditions for which disease modify therapies are
      lacking. This review provides a background in acute (i.e. brain ischemia and
      traumatic brain injury) and chronic (i.e. Alzheimer's, Parkinson's, Huntington's
      disease, amyotrophic lateral sclerosis and multiple sclerosis) neurodegenerative
      conditions. Then, the role of several kinase (i.e. JNK3, p38 MAPK, ERK, PKC,
      ROCKII, GSK3, Cdk5, MLK, EphB3 kinase, RIP1 kinase, LRRK2, TTBK1, ASK1, CK, DAPK,
      and PKN1) that could serve as potential therapeutic targets for these maladies
      are reviewed.

PMID- 19751205
TI  - RNAi applications in therapy development for neurodegenerative disease.
AB  - RNA-mediated interference (RNAi) is a powerful tool for experimental manipulation
      of gene expression and is widely used to investigate gene function both in vitro
      and in vivo. RNAi refers to an evolutionarily conserved cellular mechanism for
      sequence-specific post-transcriptional gene silencing, in which double-stranded
      RNAs promote selective degradation of homologous cellular mRNAs. Because RNAi
      based techniques can be employed to reduce expression of specific genes, this
      approach holds great promise as a therapy for diverse diseases, including
      devastating neurodegenerative disorders such as Alzheimer's, Parkinson's, and
      Huntington's diseases and amyotrophic lateral sclerosis (ALS). Importantly, in
      recent years RNAi has also emerged as a key tool in target identification and
      validation studies designed to complement traditional (i.e., small molecule
      based) drug development strategies. These studies harness the power of RNAi
      mediated reverse genetics to probe disease-associated pathways in both cell-based
      and animal models, and thus may provide critical data needed to focus drug
      development efforts around disease-relevant targets. This review highlights
      recent progress in the preclinical development of RNAi-based therapeutics for
      neurodegenerative disease and discusses the particular challenges that disorders
      of the central nervous system (CNS) pose for this approach. It further describes
      current applications of RNAi techniques for target identification and validation
      studies and underscores the importance of this methodology to developing
      treatments for neurological diseases.

PMID- 19751206
TI  - Turning REST/NRSF dysfunction in Huntington's disease into a pharmaceutical
      target.
AB  - REST/NRSF is a transcription factor that represses transcription of several
      neuronal genes by binding to a DNA regulatory motif known as Repressor Element
      1/Neuron-restrictive silencer element (RE1/NRSE). In Huntington's Disease, an
      inherited degenerative disease affecting the brain, REST/NRSF enters
      pathologically into the nucleus of affected cells, leading to the activation of
      the RE1/NRSE sites and causing decreased transcription of several important
      neuronal genes. Following this discovery, an effort has begun by some of the
      authors aimed at identifying compounds capable of antagonizing REST/NRSF
      silencing activity. Here we will review the underlying basis for focusing
      pharmaceutical efforts on REST/NRSF-RE1/NRSE system as well as some of the
      strategies for a rational drug design approach. We will highlight approaches
      aimed at identifying or designing small molecules able to impact REST/NRSF
      nuclear translocation, its DNA binding or, more generally, the formation of the
      REST/NRSF transcriptional complex, in the attempt to restore neuronal gene
      transcription in pathological conditions of the brain.

PMID- 19751207
TI  - Histone deacetylase inhibitors and neurodegenerative disorders: holding the
      promise.
AB  - Neurodegenerative disorders (NDs) such as Huntington's disease, Alzheimer's
      disease, Parkinson disease, amyotrophic lateral sclerosis, spinal muscular
      atrophy, Friedreich's ataxia, and others are multi-factorial illnesses, in which
      many pathways (still poorly understood) act serially and in parallel to give a
      determined pathologic phenotype. Thus, presently there are no effective cures for
      these diseases. Some phenotypic as well as mechanistic features, common to the
      most of NDs, can be linked to epigenetic defects, that can lead to alteration of
      acetylation homeostasis and impairment of the histone acetyltransferase (HAT):
      histone deacetylase (HDAC) balance. Here we survey most of the recent
      applications of HDAC inhibitors in the cited NDs, and we make the point of our
      (up to now) knowledge about the involvement of singular HDAC/SIRT isoform in NDs
      and other CNS pathologies.

PMID- 19751208
TI  - An update on peptide drugs for voltage-gated calcium channels.
AB  - Voltage-gated calcium channels are one of the major ion channels distributed in
      the human central nervous system, and mediate an influx of extracellular Ca(2+)
      in response to membrane depolarization. Calcium channels are of particular
      interest in a broad range of cellular functions including cell proliferation and
      differentiation, gene expression, neurite outgrowth, transmitter and hormone
      release, and brain plasticity. The dysfunction of calcium channels is related to
      a variety of clinical disorders such as migraine, hemiplegia, and epilepsy.
      Therefore, calcium channels have gained great pharmaceutical interest as a
      privileged target class for the treatment of a wide range of human diseases. This
      review will examine the known marketed peptide drugs for calcium channels and
      address the development of some important patented peptide molecules targeting
      calcium channels.

PMID- 19751209
TI  - Toward the management of inflammation: recent developments of mPGES-1 inhibitors.
AB  - For decades, the struggle against inflammation and related disorders has
      constituted an important field in medical practice, with strategies mainly aimed
      at inhibiting compounds produced through the arachidonic acid pathway. Thus,
      specific COX-2 inhibitors or "coxibs", were recently designed, that play an
      increasing but controversial role in reducing inflammatory phenomenon. Lately,
      several patents have been generated which target the specific inhibition of the
      microsomal Prostanglandin E synthase-1 (mPGES-1). This enzyme, which was cloned
      and characterized at the end of the nineties, catalyzes under inflammatory
      stimuli the last step of PGE2 synthesis. A corpus of data is now available
      illustrating the pivotal role played by this enzyme in numerous symptoms linked
      to inflammation such as fever, anorexia or pain. The present review highlights
      the current state of knowledge of the involvement of mPGES-1 in sickness
      behaviour and in other inflammation-related disorders and summarizes the recent
      patents related to mPGES-1 and its specific inhibition.

PMID- 19751210
TI  - New frontiers in alcoholism and addiction treatment.
AB  - Drug addiction and alcoholism are behavioural disorders characterized by a
      profound alteration of several brain circuits induced by chronic drug use. Their
      treatment is yet based on empiricism and today only few pharmacological
      strategies are fully effective to control both drug use and relapse. The present
      paper reviews the most updated pharmacotherapies able to contrast both alcoholism
      and drug addiction including the new patented drugs and the future therapeutic
      trends.

PMID- 19751211
TI  - Inhibitors of the PI3K/Akt/mTOR pathway: new hope for breast cancer patients.
AB  - Aberrant activation of the PI3K/Akt/mTOR pathway is found in many types of cancer
      and thus plays a major role in breast cancer cell proliferation and anti-cancer
      drug resistance. The mechanisms involved in the activation of this pathway
      include: constitutively activated receptor tyrosine kinases (IGF/IGFR, ErbB,
      FGF/FGFR systems) leading to constitutive activation of PI3K; loss of PTEN
      function; PI3K mutations; aberrant activation of Akt, eIF4E, 4E-BP1 and p70S6K.
      These alterations trigger a cascade of biological events, from cell growth and
      proliferation to survival and migration, which contribute to tumor progression.
      Therefore, the PI3K/AKT/mTOR pathway is considered an attractive target for the
      development of novel anti-cancer molecules, and several specific tyrosine kinase
      inhibitors and signal transduction inhibitors specifically targeting the kinases
      involved in this pathway have been developed. Many of these inhibitors currently
      under clinical evaluation represent a promising approach for the treatment of
      breast cancer patients. This review provides an overview of the most recent
      patents, of pre-clinical and clinical studies of inhibitors targeting the
      different members and/or activators of the PI3K/Akt/mTOR pathway, used alone or
      in combination with other targeted agents for the treatment of breast cancer.

PMID- 19751212
TI  - Nucleic-acid-binding properties of the C2-L1Tc nucleic acid chaperone encoded by
      L1Tc retrotransposon.
AB  - It has been reported previously that the C2-L1Tc protein located in the
      Trypanosoma cruzi LINE (long interspersed nuclear element) L1Tc 3' terminal end
      has NAC (nucleic acid chaperone) activity, an essential activity for
      retrotransposition of LINE-1. The C2-L1Tc protein contains two cysteine motifs of
      a C2H2 type, similar to those present in TFIIIA (transcription factor IIIA). The
      cysteine motifs are flanked by positively charged amino acid regions. The results
      of the present study show that the C2-L1Tc recombinant protein has at least a 16
      fold higher affinity for single-stranded than for double-stranded nucleic acids,
      and that it exhibits a clear preference for RNA binding over DNA. The C2-L1Tc
      binding profile (to RNA and DNA) corresponds to a non-co-operative-binding model.
      The zinc fingers present in C2-L1Tc have a different binding affinity to nucleic
      acid molecules and also different NAC activity. The RRR and RRRKEK [NLS (nuclear
      localization sequence)] sequences, as well as the C2H2 zinc finger located
      immediately downstream of these basic stretches are the main motifs responsible
      for the strong affinity of C2-L1Tc to RNA. These domains also contribute to bind
      single- and double-stranded DNA and have a duplex-stabilizing effect. However,
      the peptide containing the zinc finger situated towards the C-terminal end of C2
      L1Tc protein has a slight destabilization effect on a mismatched DNA duplex and
      shows a strong preference for single-stranded nucleic acids, such as C2-L1Tc.
      These results provide further insight into the essential properties of the C2
      L1Tc protein as a NAC.

PMID- 19751213
TI  - Mechanistic insights into Cu(I) cluster transfer between the chaperone CopZ and
      its cognate Cu(I)-transporting P-type ATPase, CopA.
AB  - Multinuclear Cu(I) clusters are common in nature, but little is known about their
      formation or transfer between proteins. CopZ and CopA from Bacillus subtilis,
      which are involved in a copper-efflux pathway, both readily accommodate
      multinuclear Cu(I) clusters. Using the luminescence properties of a multinuclear
      Cu(I)-bound form of the two N-terminal soluble domains of CopA (CopAab) we have
      investigated the thermodynamic and kinetic properties of cluster formation and
      loss. We demonstrate that Cu(I)-bound forms of dimeric CopZ containing more than
      one Cu(I) per CopZ monomer can transfer Cu(I) to apo-CopAab, leading to the
      formation of luminescent dimeric CopAab. Kinetic studies demonstrated that
      transfer is a first-order process and that the rate-determining steps for
      transfer from CopZ to CopAab and vice versa are different processes. The rate of
      formation of luminescent CopAab via transfer of Cu(I) from CopZ was more rapid
      than that observed when Cu(I) was added 'directly' from solution or in complex
      with a cysteine variant of CopZ, indicating that transfer occurs via a transient
      protein-protein complex. Such a complex would probably require the interaction of
      at least one domain of CopAab with the CopZ dimer. Insight into how such a
      complex might form is provided by the high resolution crystal structure of
      Cu3(CopZ)3, a thus far unique trimeric form of CopZ containing a trinuclear Cu(I)
      cluster. Modelling studies showed that one of the CopZ monomers can be
      substituted for either domain of CopAab, resulting in a heterotrimer, thus
      providing a model for a 'trapped' copper exchange complex.

PMID- 19751214
TI  - Activity-dependent translocation of neurogranin to neuronal nuclei.
AB  - Long-term changes of synaptic plasticity depend on protein synthesis and
      transcription. Ng (neurogranin) is a small protein concentrated at dendrites and
      spines of forebrain neurons, involved in synaptic plasticity through the
      regulation of CaM (calmodulin)-mediated signalling. Ng presents a central IQ
      motif that mediates its binding to CaM and PA (phosphatidic acid) and that can be
      phosphorylated by PKC (protein kinase C). In the present manuscript, we report
      that Ng displays a strong nuclear localization when expressed in cell lines and
      hippocampal neurons, either alone or fused to GFP (green fluorescent protein; GFP
      Ng). Furthermore, using subcellular fractionation and immunocytochemical
      techniques, we were able to localize endogenous Ng in the nuclei of rat forebrain
      neurons. Nuclear localization of Ng depends on its IQ motif and is reduced by
      binding to cytoplasmic CaM. Also, PKC stimulation induces a transient nuclear
      translocation of Ng in acute hippocampal slices. A similar translocation is
      observed in the neurons of the cerebral cortex and hippocampus after the
      induction of generalized seizures in adult rats. In summary, the results of the
      present study show that a fraction of rat brain Ng is localized in the neuronal
      nuclei and that synaptic activity regulates its translocation from the cytoplasm.
      The possible involvement of Ng in the regulation of intranuclear Ca2+/CaM
      dependent signalling and gene expression is discussed.

PMID- 19751215
TI  - Molecular cloning and characterization of two tropinone reductases in Anisodus
      acutangulus and enhancement of tropane alkaloid production in AaTRI-transformed
      hairy roots.
AB  - Tropane alkaloids are used medicinally as anticholinergic agents with increasing
      market demand, so the improvement and production of active components from
      medicinal plants using molecular biotechnology show great potential for
      applications that should benefit human healthcare. Two tropinone reductases
      constitute a branching point in the biosynthesis of tropane alkaloids. In the
      present paper, we report for the first time the cloning and characterization of
      two fulllength cDNAs encoding TRI (tropinone reductase I) (GenBank accession
      number EU424321) and TRII (tropinone reductase II) (GenBank(R) accession number
      EU424322) from the solanaceous plant Anisodus acutangulus by rapid amplification
      of cDNA ends. Sequence comparison indicated that AaTRI (A. acutangulus TRI) and
      AaTRII (A. acutangulus TRII) had high homology with other tropinone reductases
      from Hyoscyamus niger, Datura stramonium etc., but AaTRI and AaTRII showed
      identity of only 60.8%. Phylogenetic-tree analysis showed that AaTRI and AaTRII
      belong to different clusters and have the closest relationship with H. niger TRI
      and TRII respectively. Expression-pattern analysis showed that AaTRI and AaTRII
      were expressed in all tissues tested, including root, stem and leaf, but the
      transcript level of AaTRI was much lower than AaTRII. Expression of AaTRI and
      AaTRII could be enhanced by methyl jasmonate, with a weak effect for AaTRI and a
      strong effect for AaTRII. AaTRI-transformed hairy-root lines were accompanied by
      a mean 1.87-fold higher level of hyoscyamine and a mean 8-fold higher level of
      scopolamine compared with control roots, indicating that AaTRI is a promising
      target for genetic engineering to increase tropane alkaloid in A. acutangulus.

PMID- 19751216
TI  - Protein metabolism in leg muscle following an endotoxin injection in healthy
      volunteers.
AB  - The human endotoxin model has been used to study the early phase of sepsis. The
      aim of the present study was to assess leg muscle protein kinetics after an
      endotoxin challenge given to healthy human volunteers. Six healthy male subjects
      were studied in the post-absorptive state before and during 4 h following an
      intravenous endotoxin bolus (4 ng/kg of body weight). Primed continuous infusion
      of [(2)H(5)]phenylalanine and [(2)H(3)]3-methylhistidine in combination with
      sampling from the radial artery, femoral vein and muscle tissue were used to
      assess leg muscle protein kinetics. Both two- and three-compartment models were
      used to calculate protein kinetics. In addition 26S proteasome activity and
      protein ubiquitination were assessed. An increase in the net release of
      phenylalanine from the leg following the endotoxin challenge was observed;
      however, this phenylalanine originates from the free intracellular pool and not
      from protein. Net protein balance was unchanged, whereas both protein synthesis
      and breakdown were decreased. Degradation rates of contractile proteins were not
      affected by endotoxin, as indicated by an unchanged rate of appearance of 3
      methylhistidine from leg muscle. In addition, proteasome activity and protein
      ubiquitination were unaffected by endotoxaemia. In conclusion, intravenous
      endotoxin administration to healthy volunteers resulted in an increased release
      of free phenylalanine from skeletal muscle, whereas protein balance was
      unaffected. Both protein synthesis and breakdown were decreased to a similar
      extent.

PMID- 19751217
TI  - Torulaspora quercuum sp. nov. and Candida pseudohumilis sp. nov., novel yeasts
      from human and forest habitats.
AB  - Strains XZ-46A, XZ-105, XZ-129 and XZ-281(T) isolated from the oral cavities of
      healthy Tibetan volunteers were revealed to represent two novel ascomycetous
      yeast species by molecular taxonomic characterizations. Strain XZ-281(T) was most
      closely related to Candida humilis, but differed from the type strain of the
      species by eight (1.2%) substitutions in the 26S rRNA gene D1/D2 domain and by
      >100 (>20%) mismatches in the internal transcribed spacer (ITS) region. Strains
      XZ-46A, XZ-105 and XZ-129 had identical or similar D1/D2 and ITS sequences with
      each other and with strain 17YF(T) isolated from a leaf of an oak tree (Quercus
      sp.). The closest relative of this group was Torulaspora microellipsoides. They
      differed from the type strain of the species by five (0.9%) substitutions in the
      D1/D2 domain and >70 (>15%) mismatches in the ITS region. A sexual state was
      observed in strain 17YF(T), but not in the other four oral strains. An anamorphic
      name Candida pseudohumilis sp. nov. is proposed for strain XZ-281(T) (=AS
      2.3956(T)=CBS 11404(T)) and a teleomorphic name Torulaspora quercuum sp. nov. is
      proposed for strain 17YF(T) (=AS 2.3768(T)=CBS 11403(T)) and the other three oral
      strains.

PMID- 19751218
TI  - Feedback effects of host-derived adenosine on enteropathogenic Escherichia coli.
AB  - Enteropathogenic E. coli (EPEC) is a common cause of diarrhea in children in
      developing countries. After adhering to intestinal cells, EPEC secretes effector
      proteins into host cells, causing cell damage and eventually death. We previously
      showed that EPEC infection triggers the release of ATP from host cells and that
      ATP is broken down to ADP, AMP, and adenosine. Adenosine produced from the
      breakdown of extracellular ATP triggers fluid secretion in intestinal monolayers
      and may be an important mediator of EPEC-induced diarrhea. Here we examined
      whether adenosine has any effects on EPEC bacteria. Adenosine stimulated EPEC
      growth in several types of media in vitro. Adenosine also altered the pattern of
      EPEC adherence to cultured cells from a localized adherence pattern to a more
      diffuse pattern. Adenosine changed the expression of virulence factors in EPEC,
      inhibiting the expression of the bundle-forming pilus (BFP) and enhancing
      expression of the EPEC secreted proteins (Esps). In vivo, experimental
      manipulations of adenosine levels had strong effects on the outcome of EPEC
      infection in rabbit intestinal loops. In addition to its previously reported
      effects on host tissues, adenosine has strong effects on EPEC bacteria,
      stimulating EPEC growth, altering its adherence pattern, and changing the
      expression of several important virulence genes. Adenosine, like noradrenaline,
      is a small, host-derived molecule that is utilized as a signal by EPEC.

PMID- 19751219
TI  - Family 6 carbohydrate-binding modules display multiple beta1,3-linked glucan
      specific binding interfaces.
AB  - Noncatalytic carbohydrate-binding modules (CBMs), which are found in a variety of
      carbohydrate-degrading enzymes, have been grouped into sequence-based families.
      CBMs, by recruiting their appended enzymes onto the surface of the target
      substrate, potentiate catalysis particularly against insoluble substrates. Family
      6 CBMs (CBM6s) display unusual properties in that they present two potential
      ligand-binding sites termed clefts A and B, respectively. Cleft B is located on
      the concave surface of the beta-sandwich fold while cleft A, the more common
      binding site, is formed by the loops that connect the inner and the outer beta
      sheets. Here, we report the biochemical properties of CBM6-1 from Cellvibrio
      mixtus CmCel5A. The data reveal that CBM6-1 specifically recognizes beta1,3
      glucans through residues located both in cleft A and in cleft B. In contrast, a
      previous report showed that a CBM6 derived from a Bacillus halodurans
      laminarinase binds to beta1,3-glucans only in cleft A. These studies reveal a
      different mechanism by which a highly conserved protein platform can recognize
      beta1,3-glucans.

PMID- 19751220
TI  - The role and duties of scientific medical societies: The German Society of
      Dermatology from the member's perspective.
AB  - BACKGROUND: The German Society of Dermatology is a scientific medical society
      that represents the interests of German-speaking dermatology. One recommendation
      of a strategic planning mission was to increase the involvement of society
      members. METHODS: Based on an empirical approach (questionnaire survey) a
      systematic member inquiry was performed which focused on the motives for
      membership, the image of the society,the use of provided services,and
      expectations and needs. Items regarding profession and health politics,
      continuous education and specialist training, and scientific representation and
      research promotion were considered in equal measure. RESULTS: In total, 931
      usable questionnaires were available with a response rate of 28.4%. Various
      single results could be integrated in a subsequent strategic dialogue.The German
      Society of Dermatology is regarded as active and powerful in scientific issues
      and promotion of research. However, numerous expectations have been expressed to
      strengthen future activities in professional and health care related issues.
      Needs and demands differ if members are scientifically active or rather not.
      CONCLUSIONS: A scientific society in general acts in a permanent area of conflict
      and has to deal with multiple positions and interests.Thereby members' needs and
      demands may vary dependent on individual and professional backgrounds. Members
      who are not scientifically active should be more integrated in the society while
      at the same time the society's aims should be coordinated with that of the
      Berufsverband (organization of practicing dermatologists). Better networking is
      required both within the society and with outside groups. In addition, the
      primary aims and objectives of the society should be made even clearer to all
      interested parties.

PMID- 19751221
TI  - Periorbital dermatitis: causes, differential diagnoses and therapy.
AB  - Periorbital dermatitis is common and frequently difficult to treat. Patients with
      periorbital dermatitis often suffer severely because their disease is in such a
      visible location. Because of the variety of clinical appearance, the differential
      diagnostic considerations are often difficult. We examined the causes of
      periorbital dermatitis and compared the data of 88 patients from the Department
      of Dermatology, University Hospital Erlangen to those of the German IVDK
      (Information Network of the Departments of Dermatology). Between 1999 and 2004,
      predominant causes of periorbital dermatitis were allergic contact dermatitis
      (Erlangen 44%, IVDK 32%), atopic eczema (Erlangen 25%, IVDK 14%), airborne
      contact dermatitis (Erlangen 10%, IVDK 2%) and irritant contact dermatitis
      (Erlangen 9%, IVDK 8%). Less frequent causes for secondary eczematous periocular
      skin lesions were periorbital rosacea, allergic conjunctivitis or psoriasis
      vulgaris. Female gender, atopic skin diathesis and age of 40 years and older were
      identified as risk factors for periocular dermatitis. Common elicitors of
      periorbital allergic contact dermatitis were leave-on cosmetic products (face
      cream, eye shadow) and eye drops with the usual allergens being fragrances,
      preservatives and drugs. Exact identification of relevant contact allergens and
      allergen elimination are essential for successful treatment. Calcineurin
      inhibitors are the first-line therapy for facial atopic eczema. They may be also
      effective in periocular eczematous lesions of other origins although they are not
      approved for such use.

PMID- 19751222
TI  - Hymenoptera venom allergy.
AB  - Allergic reactions to Hymenoptera stings usually present as large local reactions
      or systemic reactions with symptoms of immediate type allergy (anaphylaxis). In
      Central Europe they are predominantly elicited by stings of the honeybee or
      Vespula spp. Acute reactions are managed by symptomatic treatment. Long-term care
      includes patient education (allergen avoidance, course of action at re-sting) and
      prescription of an emergency kit for self-treatment. Venom immunotherapy is
      established as specific treatment for Hymenoptera venom allergic patients.
      Diagnosis of Hymenoptera venom anaphylaxis is based on history, skin tests and
      measurement of venom-specific serum IgE antibodies. "False negative" or "false
      positive" results are possible with all test methods. If standard tests are
      negative, additional tests using the patient's peripheral blood leucocytes can be
      useful. Venom immunotherapy is usually well tolerated. After reaching the
      maintenance dose, therapeutic efficacy should be assessed by a sting challenge
      test. If the patient again develops a systemic reaction, an increase of the
      maintenance dose (usually 200 microg are sufficient) nearly always induces
      protection. In most patients venom immunotherapy can be stopped after (3 to) 5
      years. However, if there is an increased risk of sting anaphylaxis due to intense
      allergen exposure (e.g. in beekeepers) or if there are individual risk factors
      for particularly severe reactions (especially mastocytosis and/or elevated
      baseline serum tryptase concentration, severe cardiovascular disease),
      modifications of the standard venom immunotherapy are necessary.

PMID- 19751223
TI  - Research in practice: the second barrier of the human skin.
AB  - A major function of human skin is to form an effective barrier between the
      environment and the inside of the organism. Especially important for this
      function is the activity of the physical barrier of the skin, which is mainly
      located in the stratum corneum. To improve this barrier function of the skin,
      skin protection agents are used. Recent studies have revealed that application of
      skin protection agents before exposition to xenobiotics does not generally reduce
      the percutaneous uptake of these compounds. These findings indicate that besides
      new study designs and improved test systems, there seems to be a need for new
      therapeutic approaches for more effective skin protection. In this light, new
      findings regarding a second barrier function of the human skin, the
      biochemical/toxicological barrier, could be of interest. A crucial part of this
      barrier function are members of the cytochrome P450 (CYP) family and efflux
      transport proteins of the multidrug resistance-related protein family (MRPs),
      which are mainly expressed by basal layer keratinocytes. Recent studies have
      revealed that besides the physiological and protective function of these
      transport proteins and CYP enzymes in skin cells, the same proteins also play a
      role in the transport of contact allergens and activation of prohaptens to
      haptens causing contact dermatitis. Inhibition of this metabolism mediated
      activation of prohaptens and stimulation of the active elimination of contact
      allergens from skin cells could represent novel mechanisms improving the
      established tools for skin protection.

PMID- 19751224
TI  - Photopheresis in pediatric patients with low-body weight using the UVAR XTS
      system.
AB  - BACKGROUND: Photopheresis (ECP) with the UVAR XTS system has been limited to
      patients with a body weight > 40 kg, because extracorporeal blood volumes (ECV)
      may exceed 15% of the total blood volumes in low-body-weight patients. Because of
      these instrument characteristics, the use of ECP is limited in pediatric
      patients. PATIENTS AND METHODS: In 5 patients (age 4 to 15 years) with graft
      versus-host disease and with a body weight between 13 and 34 kilograms,
      photopheresis was performed using the UVAR XTS system. In 3 patients ECP could be
      performed by balancing the ECV with saline infusions. In 2 patients the system
      was modified in that the instrument was primed with packed red cells. During the
      treatment, fluid balance was guaranteed by a reservoir from a transfusion bag
      connected in parallel. RESULTS: Together 223 procedures were performed, among
      them 28 with the modification of the system. The treatments were well tolerated,
      and no episodes of hypotension were observed. CONCLUSIONS: It is possible to run
      ECP in low-body weight patients with the UVAR XTS system.

PMID- 19751225
TI  - Deletion of the inducible nitric oxide synthase gene reduces peripheral morphine
      tolerance in a mouse model of chronic inflammation.
AB  - The implication of inducible nitric-oxide synthase (iNOS) on peripheral tolerance
      to morphine was evaluated in wild-type (WT) and iNOS knockout mice. Chronic
      inflammation was induced by subplantar (s.p.) injection of Complete Freund's
      Adjuvant (CFA), and morphine tolerance by subcutaneous implantation of a 75 mg
      morphine-pellet. Withdrawal was assessed after the intraperitoneal injection of 2
      mg/kg naloxone. Antinociception was assessed (Randall-Selitto test) 5 min after a
      fixed dose of s.p. morphine (16 microg). In the absence of inflammation, s.p.
      morphine did not induce antinociception, while during CFA-inflammation produced
      47.4 +/- 0.8 and 38.8 +/- 2.7% inhibitions respectively, in each genotype (P <
      0.05). In morphine-tolerant mice with CFA-inflammation, no antinociception could
      be elicited in WT mice (2.4 +/- 0.3% inhibition); however, iNOS knockout mice
      showed significant antinociception (33.1 +/- 0.9%) (P < 0.001). Thus, iNOS gene
      deletion partially prevented tolerance to the peripheral effects of morphine, and
      significantly attenuated withdrawal-induced hyperactivity.

PMID- 19751226
TI  - Aberrant expression of synaptophysin in two metastatic alveolar
      rhabdomyosarcomas. Pitfalls in fine needle aspiration cytology diagnosis.

PMID- 19751227
TI  - Oral lesions in lupus erythematosus-cytokines profiles of inflammatory
      infiltrate.
AB  - BACKGROUND: Lupus erythematosus (LE) is a chronic inflammatory disease. Presence
      of type 1 cytokines in cutaneous discoid lesions suggests that they may be
      critical for induction, development and maintenance of these manifestations. Type
      2 cytokines in combination with local interferon gamma (INF-gamma) are thought to
      be related to the physiopathology of cutaneous LE. Cytokines profiles are still
      unknown in oral LE lesions. MATERIALS AND METHODS: Expression of Th1 and Th2
      cytokines (including IL-4, IL-5, IL-6, IL-10, IL-12, tumor necrosis factor alpha
      (TNF-alpha) and INF- gamma was investigated and compared in 29 biopsies of intra
      oral (sun-protected) and labial lesions (sun-exposed) of LE using
      immunohistochemistry. RESULTS: Inflammatory infiltrate of LE lesions was strongly
      positive for IFN- gamma (97%) and TNF-alpha (90%), both Th1 type cytokines.
      Interleukin-10, a Th2 cytokine was also strongly expressed. Other cytokines were
      only mildly positive. Cytokines patterns were similar in intra-oral (sun-covered)
      and labial (sun-exposed) LE lesions. CONCLUSIONS: Oral LE lesions are associated
      with both type 1 and type 2 cytokines, characterized by stronger expression of
      INF- gamma, TNF- alpha and IL-10. These findings suggest that although
      ultraviolet (UV) light is involved in the induction of LE lesions, mechanisms of
      lesions formation may be similar in sun-exposed as well as sun-covered areas.

PMID- 19751228
TI  - Histopathology of a granulomatous lobular panniculitis in acute Q fever: a case
      report.
AB  - Q fever is a zoonotic infection caused by Coxiella burnetii. Two forms of the
      disease have been described: an acute form with pneumonia, hepatitis or a flu
      like syndrome; and a chronic form in which endocarditis is the most frequent
      clinical expression. We report a 77 year old male with fever and an erythematous
      nodule on the right leg. Biopsy revealed a granulomatous lobular panniculitis
      with some granulomas rimmed by an eosinophilic material, giving a "doughnut" or
      "fibrin-ring" appearance. Q fever serological studies were positive. Cutaneous
      signs, among them panniculitis, are probably underestimated during the acute
      phase of the disease, and recognizing different granulomatous patterns may
      contribute to the diagnosis.

PMID- 19751229
TI  - Signet ring squamous cell carcinoma--the forgotten variant: case report and
      review of the literature.
AB  - Squamous cell carcinoma is one of the commonest skin cancers. In most instances,
      histological diagnosis is straightforward and does not pose any diagnostic
      challenge to the handling pathologist. We report a rare case of signet ring
      squamous cell carcinoma (SRSCC) occurring in an 84-year-old woman who presented
      with a sore on the upper lip. Excision of the lesion showed signet ring carcinoma
      within a scar and surface ulceration. Deeper sections showed focal area of
      squamous differentiation. Although rare, consideration of squamous cell carcinoma
      as a diagnosis of primary skin tumors with signet ring morphology, especially in
      the absence of history of adenocarcinoma, may prevent missing rare cases of
      SRSCCs.

PMID- 19751230
TI  - A new locus for hereditary hypotrichosis simplex maps to chromosome 13q12.12
      approximately 12.3 in a Chinese family.
AB  - BACKGROUND: Hereditary hypotrichosis simplex (MIM 146520, HHS) is a rare form of
      nonsyndromic alopecia. The locus for autosomal dominant HHS was mapped to
      18p11.32-p11.23 and 6p21.3, respectively, suggestive of genetic heterogeneity.
      AIM: To identify the disease-causing gene for a four-generation Chinese family
      with dominant transmission of a form of HHS. The work was carried out at State
      Key Laboratory of Medical Genomics. METHODS: Genome-wide screening was carried
      out in a Chinese family with HHS using microsatellite markers, and linkage
      analysis was performed using the MLINK program. RESULTS: The highest two-point
      logarithm of the odds (LOD) score was obtained with the microsatellite marker
      D13S217 (LOD score of 4.041 at theta = 0.00). After fine mapping and haplotype
      analysis, we defined a critical region of about 9.57 cM flanked by markers
      D13S1243 and D13S1299. The disease-causing gene was mapped to 13q12.12
      approximately 12.3 in this family. CONCLUSIONS: A novel locus for HHS maps to
      chromosome 13q12.12 approximately 12.3 in a Chinese family.

PMID- 19751231
TI  - Complete resolution of intractable pouchitis in an obese patient following
      laparoscopic gastric banding.

PMID- 19751232
TI  - Perception and practice of child labour among parents of school-aged children in
      Ibadan, southwest Nigeria.
AB  - BACKGROUND: The problem of child labour has lingered on in many countries because
      of the complex combination of social, cultural and economic factors involved.
      Parents play a critical role in child labour as it provides much needed extra
      income for the family. This study was carried out among parents of school-aged
      children in an urban, low-income community to determine the factors associated
      with child labour and attitudes to child labour in the community. METHODS: A
      cross-sectional study was carried out in an urban community in Ibadan, southwest
      Nigeria. Questionnaires were administered to parents of school-aged children.
      RESULTS: A total of 473 parents were interviewed. They were aged between 23 and
      56 years, mean 37.9 years. Thirty-nine per cent of parents indicated that they
      thought their school-aged children should work. More women than men, those from
      polygamous homes and those with lower educational status held this view. Reasons
      given for wanting their children to work were to supplement family income, 45%,
      to gain experience, 35% and to help in family business, 10%. In all, 236 (50%)
      respondents reported that their school-aged children were working. Parental
      factors associated with practice of child labour were polygamous marriage, low
      educational status, unskilled or partly skilled occupation and large family size.
      Seventeen per cent of parents with working children were not satisfied with their
      children's work conditions and complained of low earnings, long working hours,
      work on school days and unsafe work environment. Measures suggested to control
      child labour include addressing the issue of household poverty, public
      enlightenment about the ills of child labour and free education up to junior
      secondary level. Enforcement of child labour laws was the least mentioned.
      CONCLUSION: We conclude that control of child labour should be a multifaceted
      approach involving poverty alleviation, family planning to reduce family size and
      free, compulsory education up to junior secondary level. Public enlightenment
      especially for mothers will be of additional benefit.

PMID- 19751233
TI  - Are paediatricians aware of the Driver and Vehicle Licensing Agency guidance for
      common medical conditions?

PMID- 19751234
TI  - Efficiency of the home parental programme in visual-motor home activity among
      first-grade children.
AB  - BACKGROUND: The objectives of this study were to assess the efficacy of the home
      parental programme (HPP) in improving children's visual-motor skills, and to
      assess parent satisfaction with the programme. METHODS: Forty-five children and
      their parents participated in the study: 23 children and their parents in the
      study group (children receiving consultation in the classroom and whose parents
      participated in the HPP) and 22 children and their parents in the control group
      (children receiving consultation in the classroom only). All children were
      recruited based on their scores on the Visual Motor Integration test or upon
      teacher referral. The Developmental Test of Visual Perception-2 administered
      before and after intervention served as an outcome measure. HPP lasted
      approximately 12 weeks and included relevant visual-motor activities carried out
      at home by the parents with their children. RESULTS: The study failed to prove
      that HPP improved children's visual-motor skills beyond the other service
      delivery methods used in the present study. CONCLUSIONS: Parent satisfaction was
      significantly higher among those who participated in the HPP. Parents showed high
      compliance with the friendly programme despite their low socio-economic status.

PMID- 19751235
TI  - Human leukocyte antigen class I down-regulation in muscle-invasive bladder
      cancer: its association with clinical characteristics and survival after
      cystectomy.
AB  - Using a novel monoclonal anti-pan human leukocyte antigen (HLA) class I heavy
      chain antibody (EMR 8-5) reacting with paraffin-embedded sections, we examined
      the prognostic significance of HLA class I molecules in muscle-invasive bladder
      cancer patients who underwent radical cystectomy. Immunohistochemical staining
      for HLA class I molecules with monoclonal antibody EMR 8-5 was performed on
      specimens from 65 clinically muscle-invasive bladder cancer patients who
      underwent radical cystectomy and pelvic lymph node dissection without neoadjuvant
      chemotherapy. We analyzed the clinicopathological and prognostic significance of
      HLA class I expression. Immunohistochemical analysis revealed HLA class I down
      regulation in 22 (33.8%) invasive bladder cancers. This down-regulation had no
      correlation with clinicopathological parameters such as pathologic stage, nodal
      status, and grade. The recurrence-free survival of patients with HLA class I
      positive tumors was significantly better than that of those with down-regulation
      (log rank, P = 0.0337). Multivariate analysis revealed that HLA class I
      expression was a significant factor influencing the recurrence-free survival of
      bladder cancer patients after cystectomy (P = 0.0155). Our data demonstrate that
      HLA class I down-regulation in tumor cells was clearly observed in about one
      third of the patients. HLA class I expression could be a prognostic marker for
      muscle-invasive bladder cancer patients after cystectomy.

PMID- 19751236
TI  - Antitumor effect of photodynamic therapy with chlorin-based photosensitizer DH-II
      24 in colorectal carcinoma.
AB  - While photodynamic therapy (PDT) has been recognized as a promising therapeutic
      modality for the treatment of various cancers and diseases, developments of
      effective photosensitizers are highly desired to improve the prospect for the use
      of PDT. In this study, we evaluated DH-II-24, a new photosensitizer, for
      antitumor PDT in vitro and in vivo. Loaded into human colorectal carcinoma cells
      (HCT116), DH-II-24 was primarily accumulated in mitochondria, lysosomes, and
      endoplasmic reticula. Administration of DH-II-24 followed by light exposure
      induced necrotic cell death in a dose-dependent manner, whereas DH-II-24 in the
      absence of light induced minimal cell death. In order to investigate the
      distribution and phamacokinetics of the photosensitizer in vivo, DH-II-24 was
      intravenously injected to female BALB/c nude mice. Fluorescence imaging in vivo
      showed that DH-II-24 was rapidly distributed across the entire body and then
      mostly eliminated at 24 h. Next, effectiveness of DH-II-24-mediated PDT was
      examined on colorectal carcinoma xenografts established subcutaneously in BALB/c
      nude mice. DH-II-24 (1 mg/kg, i.v. administration) followed by light exposure
      significantly suppressed growth of xenograft tumors, compared to light exposure
      or DH-II-24 alone. Histological examination revealed necrotic damage in PDT
      treated tumors, concomitantly with severe damage of tumor vasculature. These
      results suggest that DH-II-24 is a potential photosensitizer of photodynamic
      therapy for cancer.

PMID- 19751237
TI  - Clinical value of minor responses after 4 doses of rituximab in Waldenstrom
      macroglobulinaemia: a follow-up of the Eastern Cooperative Oncology Group E3A98
      trial.
AB  - Waldenstrom macroglobulinaemia is a low-grade, lymphoplasmacytic lymphoma that is
      responsive to rituximab. We report the role of a minor response in predicting
      overall outcomes. We extended follow-up of a previously described cohort (n = 69)
      treated with 4 weekly doses of rituximab and observed durable responses (median
      time to progression, 30 months; 5-year survival rate, 66%). Patients achieving a
      minor response [25-50% immunoglobulin M (IgM) reduction] appeared to do as well
      as those achieving an objective response (>50% IgM reduction), which suggests
      that more aggressive or intensive therapy for minor responders is not required.
      Future studies of Waldenstrom macroglobulinaemia should report minor responses
      because they are associated with clinically meaningful benefits. This trial was
      registered at http://www.clinicaltrials.gov as #NCT00005609.

PMID- 19751238
TI  - In vitro anti-myeloma activity of the Aurora kinase inhibitor VE-465.
AB  - This study characterized the preclinical anti-myeloma activity of VE465, a low
      molecular weight pan-Aurora kinase inhibitor. After 96-h drug exposure, several
      multiple myeloma (MM) cell lines were more sensitive to VE465 compared to non
      malignant cells. The anti-MM activity of VE465 was maintained in the presence of
      interleukin-6 and, interestingly, enhanced by co-culture with stromal cells.
      However, primary MM cells were less responsive than cell lines. Combinations with
      dexamethasone (Dex), doxorubicin (Doxo) and bortezomib showed no antagonism. Our
      study highlights the potential role of the tumour microenvironment in modulating
      the activity of this drug class.

PMID- 19751239
TI  - Suppression of the hepcidin-encoding gene Hamp permits iron overload in mice
      lacking both hemojuvelin and matriptase-2/TMPRSS6.
AB  - Hepcidin, the master regulator of enteric iron absorption, is controlled by the
      opposing effects of pathways activated in response to iron excess or iron
      attenuation. Iron excess is regulated through a pathway involving the cell
      surface receptor hemojuvelin (HFE2) that stimulates expression of the hepcidin
      encoding gene (HAMP). Iron attenuation is countered through a pathway involving
      the hepatocyte-specific plasma membrane protease matriptase-2 encoded by TMPRSS6,
      leading to suppression of HAMP expression. The non-redundant function of
      hemojuvelin and matriptase-2 has been deduced from the phenotype imparted by
      mutations of HFE2 and TMPRSS6, which cause iron excess and iron deficiency
      respectively. Hemojuvelin is positioned to be the ideal substrate for matriptase
      2. To examine the relationship between hemojuvelin and matriptase-2 in vivo, we
      crossed mice lacking the protease domain of matriptase-2 with mice lacking
      hemojuvelin. Mice lacking functional matriptase-2 and hemojuvelin exhibited low
      Hamp (Hamp1) expression, high serum and liver iron, and high transferrin
      saturation. Surprisingly, the double mutant mice also exhibited lower levels of
      iron in the heart compared to hemojuvelin-deficient mice, demonstrating a
      possible cardioprotective effect resulting from the loss of matriptase-2. This
      phenotype is consistent with hemojuvelin being a major substrate for matriptase
      2/TMPRSS6 protease activity.

PMID- 19751241
TI  - Acceleration of permeability barrier recovery by exposure of skin to 10-30 kHz
      sound.
AB  - BACKGROUND: Previous reports show that ultrasound can influence human brain
      electrical activity and systemic hormone levels in various parts of the body,
      other than the ear, so there may be an unknown ultrasound-responsive system in
      humans. OBJECTIVES: In the present study, we examined the effects of sound on
      skin permeability barrier homeostasis. METHODS: We broke the skin barrier of
      hairless mice by tape stripping, and then exposed the skin to sound for 1 h to
      evaluate the effect on barrier recovery rate. RESULTS: Exposure of skin to sound
      at frequencies of 10, 20 and 30 kHz for 1 h accelerated barrier recovery, and 20
      kHz sound induced the fastest recovery. Application of 5 kHz sound had no effect
      on barrier recovery rate. Significant acceleration was observed even when the
      sound source was located 3 cm away from the skin surface. The recovery rate
      depended on the sound pressure. An electron-microscopic study indicated that
      lamellar body secretion between stratum corneum and stratum granulosum was
      increased by exposure to sound at 20 kHz. CONCLUSIONS: These results suggest that
      epidermal keratinocytes might be influenced by ultrasound in a manner that
      results in modulation of epidermal permeability barrier homeostasis.

PMID- 19751240
TI  - Bi-directional activation between mesenchymal stem cells and CLL B-cells:
      implication for CLL disease progression.
AB  - It was hypothesized that contact between chronic lymphocytic leukaemia (CLL) B
      cells and marrow stromal cells impact both cell types. To test this hypothesis,
      we utilized a long-term primary culture system from bone biopsies that reliably
      generates a mesenchymal stem cell (MSC). Co-culture of MSC with CLL B-cells
      protected the latter from both spontaneous apoptosis and drug-induced apoptosis.
      The CD38 expression in previously CD38 positive CLL B-cells was up-regulated with
      MSC co-culture. Upregulation of CD71, CD25, CD69 and CD70 in CLL B-cells was
      found in the co-culture. CD71 upregulation was more significantly associated with
      high-risk CLL, implicating CD71 regulation in the microenvironment predicting
      disease progression. In MSC, rapid ERK and AKT phosphorylation (within 30 min)
      were detected when CLL B-cells and MSC were separated by transwell; indicating
      that activation of MSC was mediated by soluble factors. These findings support a
      bi-directional activation between bone marrow stromal cells and CLL B-cells.

PMID- 19751242
TI  - Circulating IgA and IgE autoantibodies in antilaminin-332 mucous membrane
      pemphigoid.
AB  - BACKGROUND: Antilaminin-332 mucous membrane pemphigoid (MMP) is a chronic
      autoimmune bullous disease that is often associated with internal malignancy. IgG
      autoantibodies against laminin-332 in patients with MMP are well documented;
      however, IgA and IgE autoantibodies against laminin-332 have not yet been
      described. OBJECTIVES: To characterize IgA and IgE autoantibodies binding to
      laminin-332 in sera from patients with antilaminin-332 MMP. METHODS: Sera and
      skin samples from four patients who met the following criteria were used: (i)
      subepidermal blistering lesions present on the mucous membranes; (ii) in vivo
      deposition of IgG along the epidermal basement membrane zone of sampled skin;
      (iii) circulating IgG antibasement membrane zone antibodies that react with the
      dermal side of salt-split normal human skin; and (iv) circulating IgG
      autoantibodies that do not show positivity against type VII collagen or 200-kDa
      protein (p200 antigen) in immunoblot analysis using dermal extracts. Circulating
      IgG/IgA/IgE class autoantibodies against laminin-332 were determined by
      immunoblotting. RESULTS: Circulating IgG autoantibodies against the gamma2,
      alpha3/gamma2, alpha3 and alpha3/beta3/gamma2 subunits of laminin-332 were
      demonstrated in sera from four patients, respectively. Serum from one of the four
      patients showed IgA reactivity with the alpha3/beta3/gamma2 subunits of laminin
      332. Serum from one of the four patients showed IgE reactivity with the gamma2
      subunit of laminin-332. The control sera failed to display IgG/IgA/IgE reactivity
      to laminin-332. CONCLUSIONS: In addition to IgG autoantibodies, circulating IgA
      and IgE autoantibodies against laminin-332 are detectable in a subset of patients
      with antilaminin-332 MMP.

PMID- 19751243
TI  - The tumor of the third ventricle.

PMID- 19751244
TI  - Intramedullary solitary fibrous tumor of dorsal spinal cord.
AB  - Solitary fibrous tumors (SFT) are rare neoplasms of mesenchymal origin involving
      soft tissues, mainly serosal sites; the spinal cord location is uncommon. We
      report a case of SFT occurring in the thoracic spinal cord, discussing
      histological, ultrastructural and molecular aspects. A 75-year-old woman with an
      MRI suggesting a dorsal intracanalar lesion was admitted to our institution. T5
      T7 laminectomies were performed and an intramedullary tumor was discovered. The
      tumor arose within the spinal cord and was completely removed. Tumor samples were
      processed for histological, ultrastructural and molecular analysis (comparative
      genomic hybridization [CGH], methylation status of O6-methylguanine-DNA
      methyltransferase [MGMT], p16, deleted in colorectal cancer [DCC] and death
      associated protein kinase 1 [DAPK1]). The histological examination demonstrated a
      proliferation of spindle-shaped cells with a collagen-matrix background.
      Immunohistochemical staining was positive for vimentin and CD34 and negative for
      S-100 and epithelial membrane antigen. A histological diagnosis of SFT was made.
      The ultrastructural examination showed undifferentiated cells within a
      collagenous matrix and sparse extravascular basement membrane. CGH analysis
      revealed deletion of 9p21 and losses on 2q, 3p, 16q and 19q and gains on 7q;
      furthermore, no aberrant methylation pattern was found in the promoter region of
      MGMT, p16, DCC and DAPK1 genes. On the second-year follow-up, the patient was
      neurologically intact. The occurrence of SFT within the spinal cord parenchyma
      and its histological characteristics demonstrate that SFTs are not restricted to
      serosal surfaces. The course of spinal cord SFT is unknown and long-term follow
      up is necessary. The histological, ultrastructural and molecular findings are
      important for the diagnosis and the authors provide a literature review of these
      aspects.

PMID- 19751245
TI  - Primary angiitis of the CNS (PACNS) with predominant cranial neuropathy and
      spinal cord involvement.
AB  - We describe a 70-year old man with a history of repeated epidural injections for
      chronic low back pain, presenting with headache, cranial nerve palsies and
      progressive myelopathy. Meningeal enhancement was initially seen in the posterior
      epidural space of the T(10)-T(12) spine on MRI. Extensive laboratory
      investigation showed normal or negative results except for persistent
      pleocytosis, elevated protein and absence of demonstrable microorganisms on CSF
      studies. Despite conventional and empirical treatments, the patient developed
      progressive neurological deterioration leading to death. Autopsy showed Primary
      angiitis of the CNS (PACNS) with predominant cranial neuropathy, spinal cord
      involvement and extensive myelomalacia.

PMID- 19751246
TI  - Synchronous meningioma and anaplastic large cell lymphoma.
AB  - Synchronous primary brain tumors are exceedingly rare. When they occur, most
      cases are associated with metastatic disease. To the best of our knowledge, we
      report the first case of an atypical meningioma infiltrated by a T-cell-primary
      central nervous system lymphoma (PCNSL), specifically anaplastic large cell
      lymphoma (ALCL). We present a novel, unifying, plausible mechanism for its origin
      based on theories in the current literature. A 65-year-old man with a history of
      near-total resection of atypical meningioma presented with a complaint of
      progressive headaches. Imaging revealed recurrent tumor. Left frontal-temporal
      craniotomy with near-total tumor resection followed by radiation was performed.
      Recurrent symptomatic tumor led to repeat left frontotemporal craniotomy with
      tumor resection and partial anterior temporal lobectomy. Part of the specimen
      showed predominantly fibrotic neoplasm composed of nests and whorls of
      meningothelial cells, highlighted by epithelial membrane antigen (EMA) staining.
      The remainder of the specimen consisted of densely cellular neoplasm centered in
      connective tissue, including areas involved by meningioma. This tumor was
      composed of moderately large lymphoid cells with large nuclei, prominent
      nucleoli, and amphophilic cytoplasm. These cells were strongly immunoreactive for
      CD3 and CD30 but remained unstained with EMA, anaplastic lymphoma kinase-1 (ALK
      1), CD15 or cytotoxic associated antigen TIA-1. Smaller mature lymphocytes,
      chiefly T-cells, were intermixed. The morphologic and immunohistochemical
      features were considered typical of anaplastic large T-cell lymphoma. The
      pathogenesis of this association may have been due to radiation-mediated
      breakdown of the blood-brain barrier with subsequent T-cell infiltration and
      proliferation. We advocate aggressive resection and long-term surveillance for
      individuals with metastasis, especially higher-grade neoplasms that receive
      radiotherapy.

PMID- 19751247
TI  - Safety assessment of prucalopride in elderly patients with constipation: a double
      blind, placebo-controlled study.
AB  - Chronic constipation is common among nursing home residents. The aim of this
      study was to evaluate safety, tolerability and pharmacokinetics of the selective
      5HT(4) receptor agonist prucalopride in elderly, chronically constipated patients
      in nursing homes. A multicentre, phase II, randomized, double-blind dose
      escalation study in 89 elderly constipated nursing home residents treated with
      placebo, 0.5, 1 or 2 mg prucalopride once daily for 28 days was analysed. Adverse
      events, vital signs, ECG, Holter monitor and pharmacokinetics were assessed
      (Clinicaltrials.gov identifier: NCT00627692). Patients' mean age was 83 years;
      88% had a history of cardiovascular diseases. Most frequent adverse events, at
      least possibly related to prucalopride, were diarrhoea and abdominal pain.
      Relative to placebo, there were no differences in vital signs, ECG corrected QT
      interval, ECG morphology parameters, or incidence of supraventricular or
      ventricular arrhythmias on Holter monitoring. Plasma prucalopride concentrations
      increased proportionally with administered dose. Prucalopride up to 2 mg once
      daily for 4 weeks was safe and well-tolerated by constipated elderly patients,
      with no differences vs placebo in ECG or a range of Holter-monitoring parameters.

PMID- 19751248
TI  - Dynamic model for multivariate markers of fecundability.
AB  - Dynamic latent class models provide a flexible framework for studying biologic
      processes that evolve over time. Motivated by studies of markers of the fertile
      days of the menstrual cycle, we propose a discrete-time dynamic latent class
      framework, allowing change points to depend on time, fixed predictors, and random
      effects. Observed data consist of multivariate categorical indicators, which
      change dynamically in a flexible manner according to latent class status. Given
      the flexibility of the framework, which incorporates semi-parametric components
      using mixtures of betas, identifiability constraints are needed to define the
      latent classes. Such constraints are most appropriately based on the known
      biology of the process. The Bayesian method is developed particularly for
      analyzing mucus symptom data from a study of women using natural family planning.

PMID- 19751250
TI  - Spatial cluster detection for weighted outcomes using cumulative geographic
      residuals.
AB  - Spatial cluster detection is an important methodology for identifying regions
      with excessive numbers of adverse health events without making strong model
      assumptions on the underlying spatial dependence structure. Previous work has
      focused on point or individual-level outcome data and few advances have been made
      when the outcome data are reported at an aggregated level, for example, at the
      county- or census-tract level. This article proposes a new class of spatial
      cluster detection methods for point or aggregate data, comprising of continuous,
      binary, and count data. Compared with the existing spatial cluster detection
      methods it has the following advantages. First, it readily incorporates region
      specific weights, for example, based on a region's population or a region's
      outcome variance, which is the key for aggregate data. Second, the established
      general framework allows for area-level and individual-level covariate
      adjustment. A simulation study is conducted to evaluate the performance of the
      method. The proposed method is then applied to assess spatial clustering of high
      Body Mass Index in a health maintenance organization population in the Seattle,
      Washington, USA area.

PMID- 19751251
TI  - A semiparametric missing-data-induced intensity method for missing covariate data
      in individually matched case-control studies.
AB  - In individually matched case-control studies, when some covariates are
      incomplete, an analysis based on the complete data may result in a large loss of
      information both in the missing and completely observed variables. This usually
      results in a bias and loss of efficiency. In this article, we propose a new
      method for handling the problem of missing covariate data based on a missing-data
      induced intensity approach when the missingness mechanism does not depend on case
      control status and show that this leads to a generalization of the missing
      indicator method. We derive the asymptotic properties of the estimates from the
      proposed method and, using an extensive simulation study, assess the finite
      sample performance in terms of bias, efficiency, and 95% confidence coverage
      under several missing data scenarios. We also make comparisons with complete-case
      analysis (CCA) and some missing data methods that have been proposed previously.
      Our results indicate that, under the assumption of predictable missingness, the
      suggested method provides valid estimation of parameters, is more efficient than
      CCA, and is competitive with other, more complex methods of analysis. A case
      control study of multiple myeloma risk and a polymorphism in the receptor Inter
      Leukin-6 (IL-6-alpha) is used to illustrate our findings.

PMID- 19751252
TI  - Hypospadias: risk factor patterns and different phenotypes.
AB  - OBJECTIVE: To obtain more insight into the origin of hypospadias by exploring a
      wide range of potential risk factors in a case-referent study in which a
      distinction was made between different phenotypes. PATIENTS AND METHODS: Cases
      and referents were 305 boys with hypospadias and 629 boys with middle ear
      effusion whose parents completed postal questionnaires. Hypospadias phenotype was
      classified as distal (195 boys), middle (67), and proximal (43). Adjusted odds
      ratios (OR) with 95% confidence intervals (CI) were estimated using logistic
      regression. RESULTS: Low birth weight, being a twin or triplet, mother being a
      diethylstilbestrol-daughter, fertility treatments, paternal subfertility,
      obesity, prescriptive drug use, and familial occurrence of hypospadias or
      testicular cancer were associated with hypospadias in general. For familial
      occurrence of hypospadias, there were high risk estimates for the distal and
      middle phenotypes with an OR (95%CI) of 10.4 (4.5-24.1) and 9.0 (3.1-26.0), but
      not for the proximal type at 1.8 (0.2-14.9). By contrast, the association with
      low birth weight (a proxy for placental dysfunction) seemed much stronger for
      proximal hypospadias with an OR (95%CI) of 9.1 (3.4-24.2) compared with distal
      and middle hypospadias at 2.6 (1.4-5.0) and 2.3 (0.8-6.5). There were similar
      estimates for pre-eclampsia. CONCLUSION: These findings indicate aetiological
      heterogeneity of hypospadias and provide indications for the possible mechanisms
      through which specific risk factors may interfere with penile development.

PMID- 19751253
TI  - Renal cell carcinoma with retro-aortic renal vein thrombus: a case series.
AB  - OBJECTIVE: To present three cases of tumour thrombus in the retro-aortic renal
      vein (RARV) arising from left renal cell carcinomas (RCCs), a very rare event
      (<1:1000-2000 per case) and to discuss the embryological, radiological and
      surgical aspects of this anomaly. PATIENTS AND METHODS: Three cases of RCC with
      RARV thrombus presented in a 1-month period at one institution. RESULTS: All
      three cases were identified before surgery by computed tomography (CT) urograms
      and had a successful nephrectomy. CONCLUSION: RCC in the presence of RARVs is
      rare but can be identified on CT urogram. At nephrectomy, a midline laparotomy or
      full 'rooftop incision' is recommended, and any attempt to mobilize the kidney
      before dealing with the renal pedicle should be avoided.

PMID- 19751254
TI  - Retroperitoneoscopic partial adrenalectomy for small adrenal tumours (< or =1
      cm): the Ruijin clinical experience in 88 patients.
AB  - STUDY TYPE: Therapy (case series). LEVEL OF EVIDENCE: 4. OBJECTIVE: To present
      our experience of retroperitoneoscopic partial adrenalectomy (RPA) for small
      adrenal tumours, as with modern imaging methods small adrenal lesions are being
      diagnosed more commonly, and retroperitoneoscopic adrenal surgery for small
      adrenal tumours (< or =1 cm) can be challenging. PATIENTS AND METHODS: We
      retrospectively reviewed the records of 389 consecutive retroperitoneoscopic
      adrenalectomies from September 2005 to December 2008, 88 of which were small
      adrenal tumours and treated by RPA. Ultrasonography and computed tomography (CT)
      were used in all patients before RPA, and magnetic resonance imaging or positron
      emission tomography/CT in some patients. We used RPA for adrenal tumours and
      total adrenalectomy for adrenal cancer. During the surgery, the internal part of
      the adrenal gland close to the retroperitoneum was freed first, and the whole
      adrenal tissue was dissected completely. The preoperative imaging was important
      in these procedures. RESULTS: There were no deaths; conversions to open surgery
      were necessary in four patients (4.5%), the reasons being a missing target in
      two, massive haemorrhage caused by central adrenal vein injury in one, and severe
      adhesion in one. The mean (range) size of the adrenal tumours was 0.7 (0.5-1.0)
      cm, including 69 aldosterone-producing adenomas, 11 nonfunctional adrenal
      adenomas, three Cushing syndrome, two phaeochromocytomas, two myelolipomas and
      one melanoma. The operative duration in the initial 38 cases was significantly
      longer than that in the subsequent 50 (P < 0.01). However, there was no
      significant correlation between estimated blood loss and the number of
      procedures. Tumour size did not correlate with estimated blood loss and operative
      duration. There was no significant correlation between body mass index and
      operative duration. CONCLUSION: RPA is a safe, effective and minimally invasive
      therapeutic option for patients with small adrenal tumours. With improved
      operative technique the RPA has been completed in more quickly. Freeing the
      internal part of the adrenal gland close to the retroperitoneum first, and
      exploring the whole adrenal tissue during surgery are the key points of RPA. The
      location of the small adrenal tumour can be different from that shown on imaging
      before surgery, and the abnormality of the adrenal gland should be considered.

PMID- 19751255
TI  - Structural analysis of the corpora cavernosa in patients with ischaemic priapism.
AB  - STUDY TYPE: Therapy (case series). LEVEL OF EVIDENCE: 4. OBJECTIVE: To evaluate,
      using quantitative and qualitative methods, the changes in the corpora cavernosa
      of patients with ischaemic priapism. PATIENTS AND METHODS: We obtained samples of
      corpora cavernosa from seven patients with ischaemic priapism (mean age 38 years,
      range 28-44) who had a cavernous-glandular shunt. The control tissues were
      fragments of corpora cavernosa obtained from autopsies of seven age-matched men
      who died from causes unrelated to the urogenital tract. Histochemical and
      immunohistochemical techniques were used to assess and quantify the extracellular
      matrix and smooth muscle fibres. The volumetric density of smooth muscle, elastic
      fibres and collagen were determined in corpora cavernosa. RESULTS: From the
      stereological analysis the mean (sd) values of volumetric density were: for
      collagen, control 34.76 (4.64), priapism 39.64 (2.91) (P = 0.002); elastic system
      fibres, controls 28.10 (2.85), priapism 36.10 (3.06) (P = 0.001); smooth muscle
      fibres, controls 43.37 (4.96), priapism 26.48 (5.00) (P < 0.001). There were
      significantly more fibrous elements of the connective tissue and significantly
      fewer smooth muscle fibres in the corpora cavernosa of patients with ischaemic
      priapism than in controls. CONCLUSION: Ischaemic priapism is associated with
      early and significant changes in the components of the extracellular matrix and
      smooth muscle fibres of the corpora cavernosa. This could explain the frequent
      occurrence of erectile dysfunction found in patients with ischaemic priapism.

PMID- 19751256
TI  - Serum testosterone is associated with aggressive prostate cancer in older men:
      results from the Baltimore Longitudinal Study of Aging.
AB  - STUDY TYPE: Prognosis (inception cohort). LEVEL OF EVIDENCE: 1b. OBJECTIVE: To
      evaluate the relationship between testosterone levels and the development of high
      risk prostate cancer, by prospectively examining serum androgen concentrations in
      a well-studied cohort, as the role of testosterone in prostate cancer progression
      is debated. PATIENTS AND METHODS: The study comprised 781 men in the Baltimore
      Longitudinal Study of Aging who had sex steroid measurements before a diagnosis
      of prostate cancer, or at their last visit for those without cancer (no cancer,
      636; cancer, not high risk, 109; cancer, high risk, 36). High-risk cancer was
      defined as death from prostate cancer, a prostate specific antigen (PSA) level of
      > or =20 ng/mL at diagnosis, or a Gleason score of > or =8. The hazard ratio (HR)
      of high-risk disease was determined using a Cox proportional hazards regression
      model with simple updating, and risk rates were stratified by age and tercile for
      androgens of interest based on the proportional hazards analyses. RESULTS: The
      likelihood of high-risk prostate cancer doubled per unit (0.1) increase in the
      free testosterone index (FTI) for patients aged >65 years (HR 2.07, 95%
      confidence interval, CI, 1.01-4.23; P = 0.047); the likelihood for men aged < or
      =65 years was inversely related to the FTI (HR 0.96, 95% CI 0.35-2.6; P = 0.9).
      The risk rate per person-years increased from lowest to highest tercile of FTI
      for the oldest men (age >70 years) but this trend was not apparent among younger
      men. CONCLUSION: Higher levels of serum free testosterone are associated with an
      increased risk of aggressive prostate cancer among older men. These data
      highlight the importance of prospective trials to insure the safety of
      testosterone-replacement therapy.

PMID- 19751257
TI  - Abnormal protein expression in the corpus cavernosum impairs erectile function in
      type 2 diabetes.
AB  - OBJECTIVE: To investigate the changes in corporal relaxation, intracavernous
      pressure (ICP) and associated protein expression that control normal erectile
      function in rats with type 2 diabetes (T2D), as this disease is part of the
      'metabolic syndrome' associated with a high rate of erectile dysfunction (ED) in
      men, resulting from failure of corpus cavernosum-mediated processes. MATERIALS
      AND METHODS: T2D was induced in rats by feeding them with a high-fat diet (HFD)
      followed by an injection with low-dose streptozotocin (STZ); they were then
      compared with rats that received a normal diet (ND). RESULTS: Hyperglycaemia and
      dyslipidaemia were induced in HFD + STZ rats, suggesting that T2D was
      established. The rats with T2D had associated ED, as both nonadrenergic
      noncholinergic-mediated corporal relaxation and increased ICP by cavernous nerve
      stimulation were significantly attenuated compared to the ND group. Western blot
      analysis revealed diabetes-associated lower expression of endothelial and
      neuronal nitric oxide synthase (e and nNOS), and cGMP-dependent protein kinase
      (PKG)-1alpha/beta expression in penile tissue than in the ND group. Contrary to
      the proteins that regulate corporal relaxation, there were relatively high levels
      of RhoA/Rho kinase receptor 1 (ROCK1) and ET-A receptor (ETAR) in T2D rats.
      However, the expressed level of phosphodiesterase-5 and insulin-like growth
      factor binding protein 3 was not altered significantly in response to T2D.
      CONCLUSION: Decreased expression of certain proteins that mediate the relaxant
      mechanism, associated with increased expression of certain proteins that mediate
      contractile mechanisms, might be important in the development of T2D-associated
      ED. In particular, down-regulated eNOS/nNOS/PKG1 as well as up-regulated
      ETAR/RhoA/ROCK1 might participate in the aetiology of ED in T2D.

PMID- 19751258
TI  - Urinary nerve growth factor but not prostaglandin E2 increases in patients with
      interstitial cystitis/bladder pain syndrome and detrusor overactivity.
AB  - OBJECTIVE: To compare urinary nerve growth factor (NGF) and prostaglandin E2
      (PGE2) levels among patients with detrusor overactivity (DO), increased bladder
      sensation (ISB), interstitial cystitis/bladder pain syndrome(IC/BPS) and
      controls. PATIENTS, SUBJECTS AND METHODS: Urine samples were collected from 40
      women with IC/BPS, 54 with overactive bladder (OAB) and 27 normal women as
      controls, all with a full bladder. Patients with OAB were further classified into
      subgroups of DO or IBS by urodynamic results. Urinary NGF and PGE2 levels were
      measured using an enzyme-linked immunosorbent assay. Urinary NGF and PGE2 levels
      were normalized by urinary creatinine (Cr) levels and compared among all
      subgroups. RESULTS: Urinary NGF levels were increased in the 40 women with IC/BPS
      and 23 with DO but not in 31 with IBS and the 27 controls. Mean (sd) urinary
      NGF/Cr levels were not significantly different between patients with IC/BPS, at
      1.35 (0.36), and DO, at 1.93 (0.77). Urinary NGF/Cr levels were significantly
      higher in women with IC/BPS than in women with IBS, at 0.25 (0.10) (P=0.01).
      Using receiver operating characteristic curves for assessing urinary NGF/Cr
      levels in patients with IC/BPS and IBS, IC/BPS was diagnosed with a sensitivity
      and specificity of 75% and 65.5%, respectively, based on a urinary NGF/Cr
      threshold of 0.015. However, urinary PGE2/Cr levels were not significantly
      different among all subgroups. CONCLUSIONS: Urinary NGF/Cr levels are elevated in
      women with IC/BPS or DO, but not in those with IBS. The differential diagnosis of
      women with IC/BPS from those with frequency-urgency syndrome is possible based on
      urinary NGF/Cr levels but not urinary PGE2/Cr level.

PMID- 19751259
TI  - Chronic prostatitis presenting with dysfunctional voiding and effects of pelvic
      floor biofeedback treatment.
AB  - OBJECTIVE: To investigate the features of chronic prostatitis presenting with
      dysfunctional voiding (DV) and the effects of pelvic floor biofeedback (PFB).
      PATIENTS AND METHODS: The study included 21 patients, diagnosed by having
      symptoms for > or =3 months, including urinary frequency and urgency, voiding
      difficulty, upper abdominal or perineal discomfort, and with a score of > or =1
      on the first and second part of the National Institutes of Health Chronic
      Prostatitis Symptom Index (NIH-CPSI). Patients with bacterial prostatitis,
      urethritis, interstitial cystitis, urethral stricture and neurogenic bladder were
      excluded. All patients had a urodynamic examination, to assess the uroflow curve,
      maximum urinary flow rate (Q(max)), maximum detrusor pressure during the storage
      phase (P(det.max)), maximum urethral pressure (MUP) and the maximum urethral
      closure pressure (MUCP) were recorded. PFB was carried out in patients with non
      neurogenic detrusor sphincter dyssynergia, and the effects evaluated after 10
      weeks. RESULTS: Before and after PFB treatment the mean (sd) Q(max), P(det.max),
      MUP, MUCP were 8.2 (4.1) vs 15.1 (7.3) mL/s, 125.1 (75.3) vs 86.3 (54.2) cmH(2)O,
      124.3 (23.3) vs 65.4 (23.0) cmH(2)O and 101.5 (43.6) vs 43.5 (16.7) cmH(2)O, all
      significantly different (P < 0.05). The respective differences in the pain,
      urination and life impact subdomain scores, and total scores, of the NIH-CPSI
      were 4.0 (2.0) vs 2.2 (1.7), 7.9 (2.1) vs 2.2 (1.9), 9.6 (2.7) vs 2.9 (2.6) and
      21.7 (4.8) vs 8.4 (4.6), and all differences were significant (P < 0.05).
      CONCLUSIONS: There might be DV in patients with chronic prostatitis and lower
      urinary tract symptoms. Urodynamics showed a low Q(max) and increasing
      intravesical pressure and, in some patients, increasing urethral pressure.
      Urodynamics could be used to help in the diagnosis, and to select the most
      appropriate treatment. PFB had satisfactory short-term effects on these patients.

PMID- 19751260
TI  - The West Midlands Bladder Cancer Prognosis Programme: rationale and design.
AB  - OBJECTIVE To describe the rationale and design of the Bladder Cancer Prognosis
      Programme (BCPP), and to demonstrate the capability of this design. METHODS There
      is a need to understand the determinants of bladder cancer to help reduce
      recurrence, progression, morbidity, mortality and related costs. We previously
      showed that lifestyle factors are important for determining the risk of bladder
      cancer, but little is known about their importance in determining the risk of
      recurrence or progression after diagnosis. Also, histopathological factors alone
      provide only crude prognostication; the analysis of molecular markers represents
      a method for refinement but research in this area has not been useful in
      informing therapeutic decisions or prognostication. The BCPP is a prospective
      longitudinal cohort study of all patients with newly diagnosed bladder cancer
      within the West Midlands (UK), investigating the influence of lifestyle factors
      on recurrence and progression, health-related quality of life, the predictive
      effect of a panel of molecular markers on recurrence or progression, and the
      establishment of Europe's largest comprehensive bladder cancer bio-repository. It
      also incorporates the first randomized clinical trial on the efficacy of selenium
      and vitamin E on bladder cancer. The numbers and proportions of eligible patients
      recruited, questionnaires completed and specimens obtained were all recorded.
      RESULTS Since December 2005, 771 patients have been recruited (68% of eligible
      patients) and of these, 331 are currently being followed up by questionnaires. We
      have obtained blood, urine and tumour tissues from 92%, 80% and 80% of patients,
      respectively. CONCLUSIONS The design of the BCPP has allowed this study to be
      incorporated into routine clinical work throughout the West Midlands, achieving
      high levels of recruitment, and data and specimen collection. This might
      represent a model for the future investigation of urological and other
      malignancies.

PMID- 19751261
TI  - Bladder pain syndrome/interstitial cystitis in a Danish population: a study using
      the 2008 criteria of the European Society for the Study of Interstitial Cystitis.
AB  - OBJECTIVE: To characterize and evaluate a Danish patient population with bladder
      pain syndrome/interstitial cystitis (BPS/IC), using a working definition for
      BPS/IC incorporating six variables, and a set of criteria defined by the European
      Society for the Study of Interstitial Cystitis (ESSIC); to describe the clinical
      course and treatment intensity in relation to these variables. PATIENTS AND
      METHODS: Clinical data were obtained retrospectively from medical records for 349
      consecutive patients with IC referred to the Department of Urology, Copenhagen
      University Hospital Herlev, Denmark between 1966 and 2008. The median (range) age
      at diagnosis was 53 (16-88) years; 64% were followed for at least 2 years. The
      outcome was expressed in terms of treatment intensity and was correlated with
      clinical data (pain, nocturnal frequency, bladder capacity, mucosal
      glomerulations, detrusor mastocytosis, detrusor intrafascicular fibrosis, IFF).
      RESULTS: All patients had pain and 75% had nocturia at least twice. The bladder
      capacity estimated under general anaesthesia was <500 mL in 42%; 53% presented
      with detrusor mastocytosis (> or =28 mast cells/mm(2)) and 50% with IFF. The
      detrusor mast cell count (P < 0.001), IFF (P = 0.004) and nocturnal frequency (P
      = 0.043) had statistically significant prognostic value for treatment intensity,
      whereas bladder capacity and glomerulations were not significant. CONCLUSION:
      Nocturia, detrusor mastocytosis and IFF are associated with multiple treatments
      and presumed failure of standard urological therapy in patients with BPS/IC,
      while bladder capacity and glomerulations are not. Valid conclusions cannot be
      drawn because of numerous limitations to the study.

PMID- 19751262
TI  - Developments in the surgical management of sporadic synchronous bilateral renal
      tumours.
AB  - OBJECTIVE: To examine our experience with managing sporadic bilateral renal
      masses, focusing on trends in surgical management over time, because as loss of
      renal function is associated with adverse cardiovascular outcomes, nephron
      sparing approaches are increasingly emphasized in the treatment of kidney
      tumours, creating new challenges for the treatment of bilateral tumours. PATIENTS
      AND METHODS: We identified all patients who underwent partial or radical
      nephrectomy (PN or RN) at Memorial Sloan-Kettering Cancer Center (MSKCC) during
      1989-2008. We compared patients presenting with synchronous bilateral renal
      masses with those with unilateral tumour and evaluated trends in management using
      logistic regression. RESULTS: Of the 2777 patients studied, 73 (3%) presented
      with synchronous bilateral disease. The overall survival and
      clinical/pathological features between groups were similar. Of those patients
      receiving bilateral operations for synchronous tumours, three had bilateral RN
      (all before 2003), 28 (38%) had an RN followed by a PN, 10 (14%) had a PN then an
      RN, and 32 (44%) had bilateral PN. Over time, the proportion of patients
      receiving bilateral PN increased (P < 0.001); 13 of 14 patients after 2005 had
      bilateral PN, compared with only 34% (16 of 45) between 1995 and 2004. Forty-five
      patients (62%) had the larger tumour removed during the first operation. The
      concordance rate between tumours in a specific histological subtype was 70%
      (51/73), and concordance for benign vs malignant disease was 90% (66/73).
      CONCLUSION: The use of PN in the management of synchronous bilateral renal masses
      has increased over time. The contemporary treatment of synchronous bilateral
      renal masses at MSKCC involves staged PN when feasible, with the more involved
      kidney (often larger tumour) operated on first.

PMID- 19751263
TI  - Stage migration in localized prostate cancer has no effect on the post-radical
      prostatectomy Kattan nomogram.
AB  - OBJECTIVE: To investigate the effect of prostate-specific antigen (PSA) testing
      on stage migration in an Australian population, and its consequences on the
      prognostic accuracy of the post-radical prostatectomy (RP) Kattan nomogram, as in
      North America widespread PSA testing has resulted in prostate cancer stage
      migration, questioning the utility of prognostic nomograms in this setting.
      PATIENTS AND METHODS: The study comprised 1008 men who had consecutive RP for
      localized prostate cancer between 1991 and 2001 at one institution. Two groups
      were assessed, i.e. those treated in 1991-96 (group 1, the early PSA era), and
      1997-2001 (group 2, the contemporary PSA era). Differences in clinicopathological
      features between the groups were analysed by chi-squared testing and survival
      modelling. Individual patient data were entered into the post-RP Kattan nomogram
      and the efficacy assessed by receiver- operating characteristic curve analysis.
      RESULTS: Patients in group 2 had lower pathological stage disease (P = 0.01) and
      fewer cancers with Gleason score > or =8 (P < 0.001) than group 1. Multivariate
      analysis identified preoperative serum PSA level (P < 0.01) and Gleason score (P
      < 0.01) as strong predictors of biochemical relapse in both groups. In group 2
      pathological stage was not significant, but margin involvement became highly
      significant (P = 0.004). There was no difference in the predictive accuracy of
      the Kattan nomogram between the groups (P = 0.253). CONCLUSIONS: These findings
      show a downward stage migration towards organ-confined disease after the
      introduction of widespread PSA testing in an Australian cohort. Despite this, the
      Kattan nomogram remains a robust prognostic tool in clinical practice.

PMID- 19751264
TI  - Differences in histopathological and biochemical outcomes in patients with low
      Gleason score prostate cancer.
AB  - STUDY TYPE: Diagnosis (case series). LEVEL OF EVIDENCE: 4. OBJECTIVE: To test
      whether the number or percentage of positive biopsy cores can be used to
      discriminate between patients with prostate cancer of a favourable and less
      favourable Gleason score (GS) < or =3 + 3, as prognostically, not all GS 3 + 3
      prostate cancers are the same. PATIENTS AND METHODS: In all, 1106 consecutive
      patients with a prostate-specific antigen (PSA) level of < or =10 ng/mL and a
      biopsy GS of < or =3 + 3 or 3 + 4 had an open radical prostatectomy. The number
      of positive biopsy cores (< or =2 vs > or =3) were stratified into low- vs high
      risk groups. Subsequently, we stratified patients according to the GS and the
      percentage of positive biopsy cores (<50% vs > or =50%). The pathological stage
      and the 5-year biochemical recurrence (BCR)-free survival rates were examined in
      univariable and multivariable models. RESULTS: Based on the number of positive
      cores, the rate of extraprostatic disease was 11.7% and 23.3%, respectively, in
      the low-and high-risk GS < or =3 + 3 groups (P < 0.001). The 5-year BCR-free
      survival rates were 95.0%, 77.8%, 81.2% and 66.5% for, respectively, low- and
      high-risk GS < or =3 + 3 and for low- and high-risk GS 3 + 4 patients.
      Univariable and multivariable intergroup BCR rate differences were statistically
      significant between low- vs high-risk GS 3 + 3 patients (P < 0.001), but not
      significant between high-risk GS < or =3 + 3 vs low-risk GS 3 + 4 patients (P =
      0.6). Comparable results were obtained when comparisons were made according to
      the percentage of positive biopsy cores. CONCLUSIONS: Our results corroborate the
      finding that not all patients with a biopsy GS of < or =3 + 3 prostate cancer
      have low-risk disease. High-risk GS < or =3 + 3 patients have a similar risk
      profile as more favourable GS 3 + 4 patients. This finding warrants consideration
      when deciding on treatment.

PMID- 19751265
TI  - The growth rate of large renal masses opposes active surveillance.
AB  - OBJECTIVE: To retrospectively determine the growth rate of renal masses with a
      diameter of > or =4 cm at the time of surgery, as the average growth rate of
      untreated small (<4 cm) renal masses is assumed to be 0.1-0.7 cm/year, but little
      is known about the progression of large masses. PATIENTS AND METHODS: Of 256
      patients who had their renal tumour surgically removed between January and
      December 2008, we identified nine (five men and four women; median age 65.2
      years, range 29.2-74.2) with solitary large renal masses (>4 cm) who had
      abdominal imaging with identification of renal masses >6 months before admission.
      In none of the patients had the initial imaging led to admission, either by
      accident or because the masses were overlooked. The tumour growth rate was
      calculated based on images taken > or =6 months before admission and actual
      imaging, as well as histological results. RESULTS: All patients had surgical
      resection of their renal masses in 2008. The median (range) follow-up from
      initial diagnosis to surgery was 14.6 (6.5-58.4) months. The median observed
      tumour growth rate was 6.41 (2.47-8.66) cm/year. The histological diagnosis was
      clear cell renal cell carcinoma (RCC) in seven patients, papillary in one and
      clear cell RCC with portions of sarcomatoid de-differentiation in one; two
      patients had lymph node metastases and one had pulmonary metastases, and five had
      tumours of > or =T3. CONCLUSIONS: The growth rate of large tumours is much higher
      than of small renal masses and most patients present with advanced disease. Thus,
      tumours of > or =4 cm seem not to be candidates for active surveillance but
      require immediate therapy. Further studies are warranted to determine the
      clinical relevance of progressive tumour growth and the underlying mechanisms.

PMID- 19751266
TI  - On the sorting of the repertoire: an analysis of Cohn's challenge to integrity
      (Dembic), Round 2.
AB  - In analyzing the integrity model and other context-based models, Melvin Cohn
      excluded the possibility that regulatory T cells or germline selected mechanisms
      can contribute to defining the specificity of immune responses. Here I discuss in
      greater detail how both the experimental data and a quantitative view of the
      evolution of immune control mechanisms challenge Cohn's arguments.

PMID- 19751268
TI  - A systematic review and meta-analysis of the efficacy and safety of etanercept
      for treating rheumatoid arthritis.
AB  - The aim of this study was to evaluate the efficacy and safety of etanercept (ETA)
      for treating rheumatoid arthritis. A systematic review was performed to search
      for randomized clinical trials comparing subcutaneous doses of ETA at 25 mg twice
      a week or 50 mg weekly to a placebo group, with or without methotrexate. Studies
      of low quality (less than 3 points on Jadad's scale) were excluded. The efficacy
      was assessed by using the criteria of the American College of Rheumatology (ACR).
      Safety data were evaluated based on serious adverse events, serious infections,
      malignancy and deaths. Withdrawals as a result of adverse events or lack of
      efficacy were also evaluated. Eight studies met the inclusion criteria,
      comprising 2385 patients. In the efficacy meta-analysis, a greater number of ETA
      treated patients achieved the efficacy criteria within 6 months of treatment,
      where the relative risk (RR) was 2.94 [2.27, 3.81] for achieving ACR20, 5.28
      [3.12, 8.92] for ACR50 and 4.83 [1.74, 13.47] for ACR70. After 1 year, the RR for
      achieving ACR20, ACR50 and ACR70 were 1.14 [1.07, 1.23], 1.36 [1.21, 1.53] and
      1.56 [1.30, 1.88], respectively. This response rates were higher for ETA-treated
      patients in comparison with control group patients. For safety, there were no
      statistically significant differences between treated patients and controls. This
      was also confirmed by withdrawals as a result of adverse events, which were not
      statistically different between the two groups. However, more patients withdrew
      from control groups because of a lack of efficacy as compared with ETA groups (RR
      = 0.48 [0.30, 0.78]).

PMID- 19751269
TI  - Regions of differences encoded antigens as targets for immunodiagnosis of
      tuberculosis in humans.
AB  - Tuberculosis is one of the major global health problems causing nearly 2 million
      deaths every year. It continues to be a leading cause of morbidity and mortality
      in developing countries. Accurate early diagnosis and proper treatment can
      control the spread of tuberculosis in the community. Currently used diagnostic
      tests have certain limitations such as low sensitivity and suboptimal turn-around
      times. Hence, introduction of diagnostic methods that are comparatively more
      sensitive and specific can increase the efficiency of strategies to control
      tuberculosis. In recent years, there has been a remarkable progress in
      identifying new and potentially useful antigens for diagnosis of both latent and
      active tuberculosis. Regions of differences (RD) encoded proteins are among such
      promising candidate antigens (RD antigens). Some of these antigens are encoded by
      regions of differences located in the genome of Mycobacterium tuberculosis, M.
      africanum, M. bovis but are absent in all the Bacillus Calmette Guerin substrains
      and many of the environmental mycobacteria. Over the past few years, RD antigens,
      particularly RD-based diagnostic methods such as improved tuberculin skin
      testing, interferon-gamma release assays, and RD1-based serological assays are
      being tested and have shown promising results. This article provides an overview
      of the use of RD antigens in the immunodiagnosis of tuberculosis infection and
      disease.

PMID- 19751267
TI  - How do regulatory T cells work?
AB  - CD4(+) T cells are commonly divided into regulatory T (Treg) cells and
      conventional T helper (Th) cells. Th cells control adaptive immunity against
      pathogens and cancer by activating other effector immune cells. Treg cells are
      defined as CD4(+) T cells in charge of suppressing potentially deleterious
      activities of Th cells. This review briefly summarizes the current knowledge in
      the Treg field and defines some key questions that remain to be answered.
      Suggested functions for Treg cells include: prevention of autoimmune diseases by
      maintaining self-tolerance; suppression of allergy, asthma and pathogen-induced
      immunopathology; feto-maternal tolerance; and oral tolerance. Identification of
      Treg cells remains problematic, because accumulating evidence suggests that all
      the presently-used Treg markers (CD25, CTLA-4, GITR, LAG-3, CD127 and Foxp3)
      represent general T-cell activation markers, rather than being truly Treg
      specific. Treg-cell activation is antigen-specific, which implies that
      suppressive activities of Treg cells are antigen-dependent. It has been proposed
      that Treg cells would be self-reactive, but extensive TCR repertoire analysis
      suggests that self-reactivity may be the exception rather than the rule. The
      classification of Treg cells as a separate lineage remains controversial because
      the ability to suppress is not an exclusive Treg property. Suppressive activities
      attributed to Treg cells may in reality, at least in some experimental settings,
      be exerted by conventional Th cell subsets, such as Th1, Th2, Th17 and T
      follicular (Tfh) cells. Recent reports have also demonstrated that Foxp3(+) Treg
      cells may differentiate in vivo into conventional effector Th cells, with or
      without concomitant downregulation of Foxp3.

PMID- 19751270
TI  - Reduced apoptosis of mouse macrophages induced by yscW mutant of Yersinia pestis
      results from the reduced secretion of YopJ and relates to caspase-3 signal
      pathway.
AB  - The virulence of the pathogenic Yersinia species depends on a plasmid-encoded
      type III secretion system (T3SS) that injects six Yersinia outer protein (Yop)
      effector proteins into the cytosol of macrophages, leading to disruption of host
      defence mechanisms. Here, we report that a T3SS structural protein YscW of
      Yersinia pestis contributed to the induction of apoptosis of murine macrophages.
      The apoptotic percentage of macrophages, from both mouse peritoneal cavity and
      spleen, and of RAW264.7 cell line, caused by the yscW mutant strain was
      significantly lower than that by wild type (WT) Y. pestis and yscW complemented
      strain. Meanwhile, detection of caspase-3 activity in macrophages, a key
      apoptosis-inducing protein, showed coincident results with the changes of
      macrophage apoptosis induced by WT, yscW mutant and complemented strains,
      indicating that macrophage apoptosis was related to caspase-3 signal pathways.
      However, ectopic expression of YscW in RAW264.7 cells cannot increase the
      macrophage apoptosis and death, suggesting that YscW itself could not induce
      macrophage apoptosis directly. To get insight into the mechanism of this
      phenomenon, we investigated the secretion of YopJ, which has been thought to be
      the only Yop effector related to apoptosis, in WT, mutant and complemented
      strains, respectively. Results showed that in yscW mutant strain, secretion of
      YopJ was decreased significantly in the supernatant than that in WT or
      complemented strain. This means although YscW does not induce apoptosis directly,
      it can indirectly affect apoptosis through reducing the secretion of YopJ.

PMID- 19751271
TI  - In vivo extravasated human monocytes have an altered expression of CD16, HLA-DR,
      CD86, CD36 and CX(3)CR1.
AB  - The phenotypic alterations in monocytes induced by extravasation in vivo are
      still largely unknown. We addressed the question whether a general phenotype of
      extravasated monocytes exists and whether this phenotype differs between healthy
      individuals and statin treated patients with coronary artery disease (CAD). In
      vivo extravasated monocytes from CAD patients and healthy controls were collected
      by use of the skin blister method and compared with peripheral circulating
      monocytes by flow cytometry. The number of CD14(+)CD16(+) monocytes were
      significantly higher in the skin blister compared with peripheral circulation in
      both patients (P < 0.001) and controls (P = 0.005). In vivo extravasated
      monocytes had in comparison with peripheral monocytes a lower expression of
      CX(3)CR1, a higher expression of HLA-DR, CD86 and CD36 and a higher binding of
      acetylated low density lipoprotein (acLDL) (significant for all markers). Skin
      blister fluid from CAD patients, compared with healthy controls, induced a 20%
      increase in monocyte CD36 expression (P = 0.008) following 18 h of in vitro
      incubation. The results indicate that the integrated response to the in vivo
      extravasation process is similar in statin treated stable CAD patients and
      healthy controls, with respect to phenotypic alterations. Such differences in CAD
      patients may, however, occur as a response to the inflammatory milieu.

PMID- 19751272
TI  - The CD4(+)CD8(+) and CD4(+) subsets of FOXP3(+) thymocytes differ in their
      response to growth factor deprivation or stimulation.
AB  - The timing of thymic regulatory T (Treg) cell commitment remains unclear.
      Specifically, there is disagreement as to whether the CD4(+)CD8(+) FOXP3(+)
      thymocytes are precursors of mature CD4(+) FOXP3(+) Treg cells, or an independent
      Treg cell lineage. We reasoned that precursors should be more susceptible to
      apoptosis than mature Treg cells, and tested this by growth factor removal and
      anti-CD3 stimulation. Both treatments resulted in an increase of CD4(+) FOXP3(+)
      thymocytes, whereas the frequency of CD4(+)CD8(+) FOXP3(+) thymocytes decreased
      significantly. These changes were accompanied by an increase of annexin(+)
      apoptotic cells. Both of these FOXP3(+) subsets expressed higher levels of Bcl-2
      and BIM than other thymocytes, and while in our setting expression of BIM seemed
      to predispose the cells to apoptosis, Bcl-2 had no apparent protective effect.
      These results indicate that CD4(+)CD8(+) FOXP3(+) thymocytes are more susceptible
      to apoptosis than mature CD4(+) FOXP3(+) Treg cells. This is consistent with the
      view that they are still immature and thus likely to represent a precursor
      population.

PMID- 19751273
TI  - Anomalous immunogenic properties of serine proteases.
AB  - It has previously been shown that a approximately 27 kDa serine protease of
      Schistosoma mansoni larvae, the cercarial elastase (CE), was a poor immunogen in
      as much as it failed to induce an antibody response. The CE has a critical role
      in enabling schistosome larvae to penetrate the skin of their definitive hosts,
      so the apparently poor immunogenicity of this enzyme is clearly of interest. To
      understand its lack of immunogenicity better and in particular to determine
      whether it is related to its proteolytic activity, we have measured antibody
      responses of mice to three different serine proteases. Groups of mice were
      immunized with porcine pancreatic trypsin (TRY), chymotrypsin (CHY) or elastase
      (ELA) and the resulting antibody response compared with antibody responses to two
      non-protease antigens, chicken egg albumin (OVA) and Schistosoma japonicum
      glutathione S-transferase (GST), all being administered with alum as an adjuvant.
      Of 12 mice that were injected five times at 14 day intervals with TRY, only one
      produced antibody reactive with this enzyme in ELISA. Immunizations with CHY or
      ELA induced somewhat better antibody responses than TRY, but the responses to the
      first and second injections of these two proteases nevertheless seemed
      comparatively lower than the responses to GST. Induction of antibody responses by
      OVA and GST was not affected when TRY was injected concomitantly. Thus, the
      antibody response to one of the serine proteases used in this study, mammalian
      trypsin, was anomalous.

PMID- 19751274
TI  - Effects of salivary gland homogenate from wild-caught and laboratory-reared
      Lutzomyia longipalpis on the evolution and immunomodulation of Leishmania
      (Leishmania) amazonensis infection.
AB  - We investigated the effects of Lutzomyia longipalpis salivary glands homogenate
      of wild-caught and laboratory-reared vectors on the lesion evolution and
      immunomodulation of the infection caused by Leishmania (Leishmania) amazonensis.
      To compare the effect of both salivary glands homogenate (SGH), C57BL/6 mice were
      inoculated subcutaneously into the hind footpads or into the ear dermis with
      10(6) promastigotes in the presence or not of SGH from wild-caught and laboratory
      colonized sand flies. Comparing SGH groups, the lesion size was lower in mice co
      inoculated with wild-caught SGH, as the parasitism and the infiltration of
      macrophages at the inoculation site. Wild-caught SGH also determined lower
      production of IL-4 and IL-10 but higher IL-12 levels compared with laboratory
      reared SGH. Our findings address a probable bias by using SGH from laboratory
      colonized sand flies instead of wild-caught vector SGH in studies concerning
      saliva effects. A possible mild influence of sand fly saliva in natural
      infections caused by Leishmania is also speculated, as infection is transmitted
      by wild and not by laboratory-reared vectors.

PMID- 19751275
TI  - Lipoxin A(4) metabolites/analogues from two commercial sources have no effects on
      TNF-alpha-mediated priming or activation through the neutrophil formyl peptide
      receptors.
AB  - The eicosanoid lipoxin A(4) (LXA(4)) is a potent anti-inflammatory mediator in
      many in vivo experimental models, and it has been proposed that the effects of
      this molecule are mediated through binding to FPR2 (also termed FPRL1 or ALXR), a
      member of the formyl peptide receptor family. Research has shown that LXA(4)
      inhibits neutrophil function, which has been suggested to be an important
      mechanism in the anti-inflammatory activity of this lipoxin. However, experiments
      demonstrating such an impact of LXA(4) have not always been convincing. In this
      study, we examined the influence of metabolically stable LXA(4) analogues on the
      biological activities induced by a previously characterized FPR2 agonist (WKYMWM)
      and a commonly used FPR1 agonist (fMLF). We also investigated the analogues
      regarding their direct effect on TNFalpha-mediated neutrophil mobilization of the
      complement receptor 3 (CR3) and their indirect effect on cytokine-dependent
      priming of the cells. The LXA(4) analogues we used came from two commercial
      sources. In our experiments, they did not induce any direct neutrophil response,
      nor did they affect the increase in the number of CR3 molecules on the neutrophil
      surface or the primed response. Therefore, we conclude that these LXA(4)
      analogues do not have an impact on TNF-alpha induced signalling in neutrophils.
      We also applied a recently described technique that has proven to be a valuable
      tool for identifying selective FPR1 and FPR2 agonists and antagonists. We found
      that the lipoxin analogues did not induce any changes in the neutrophil response,
      which implies that LXA(4) does not act through FPR2 in these cells.

PMID- 19751276
TI  - The elevated interferon gamma production is an important immunological marker in
      HAM/TSP pathogenesis.
AB  - Human T-lymphotropic virus type 1 (HTLV-1) is the agent of the HTLV-1-associated
      myelopathy/tropical spastic paraparesis (HAM/TSP), which may occur in >5% of
      patients during their lifetime. HTLV-1-infection causes disturbances in the
      immune system, and the viral load may also play an important role in the
      pathogenesis of HAM/TSP. Some cytokines are involved in the pathogenesis of this
      disorder. We have determined IL-2, IL-4, IL-10, IL-12 p70, IFN-gamma and TNF
      alpha production among HTLV-1-infected subjects from our HTLV-out Clinic in
      Institute of Infectious 'Emilio Ribas' in Sao Paulo city, Brazil. PBMC obtained
      from healthy controls (n = 32), asymptomatic HTLV-1 carriers (n = 68) and HAM/TSP
      patients (n = 44) were grown in the absence and in the presence of
      phytohaemagglutinin (PHA), and the supernatants' fluids were measured for
      cytokines production. IL-2 levels were increased in the asymptomatic HTLV-1
      carriers, and IFN-gamma was increased in both groups of patients (asymptomatic
      HTLV-1 carriers and more significantly among HAM/TSP patients). IL-4, IL-10, TNF
      alpha and IL-12 p70 levels were not significantly increased on both groups of
      patients, as compared with controls. The major finding of this study is that IFN
      gamma was an important cytokine for the HAM/TSP pathogenesis. Therefore, immune
      modulation of IFN-gamma may be critical to treat of HAM/TSP patients.

PMID- 19751277
TI  - Folate-metabolizing genes in lymphoma patients from Sweden.

PMID- 19751279
TI  - Tracking diabetes: New York City's A1C Registry.
AB  - CONTEXT: In December 2005, in characterizing diabetes as an epidemic, the New
      York City Board of Health mandated the laboratory reporting of hemoglobin A1C
      laboratory test results. This mandate established the United States' first
      population-based registry to track the level of blood sugar control in people
      with diabetes. But mandatory A1C reporting has provoked debate regarding the role
      of public health agencies in the control of noncommunicable diseases and, more
      specifically, both privacy and the doctor-patient relationship. METHODS: This
      article reviews the rationale for adopting the rule requiring the reporting of
      A1C test results, experience with its implementation, and criticisms raised in
      the context of the history of public health practice. FINDINGS: For many decades,
      public health agencies have used identifiable information collected through
      mandatory laboratory reporting to monitor the population's health and develop
      programs for the control of communicable and noncommunicable diseases. The
      registry program sends quarterly patient rosters stratified by A1C level to more
      than one thousand medical providers, and it also sends letters, on the provider's
      letterhead whenever possible, to patients at risk of diabetes complications (A1C
      level >9 percent), advising medical follow-up. The activities of the registry
      program are similar to those of programs for other reportable conditions and
      constitute a joint effort between a governmental public health agency and medical
      providers to improve patients' health outcomes. CONCLUSIONS: Mandatory reporting
      has proven successful in helping combat other major epidemics. New York City's
      A1C Registry activities combine both traditional and novel public health
      approaches to reduce the burden of an epidemic chronic disease, diabetes. Despite
      criticism that mandatory reporting compromises individuals' right to privacy
      without clear benefit, the early feedback has been positive and suggests that the
      benefits will outweigh the potential harms. Further evaluation will provide
      additional information that other local health jurisdictions may use in designing
      their strategies to address chronic disease.

PMID- 19751280
TI  - Commentary: Beyond historical precedent.

PMID- 19751281
TI  - Commentary: A legal perspective on diabetes surveillance--privacy and the police
      power.

PMID- 19751282
TI  - Commentary: Public health and health care quality assurance--strange bedfellows?

PMID- 19751283
TI  - Comparative effectiveness research in Ontario, Canada: producing relevant and
      timely information for health care decision makers.
AB  - CONTEXT: Comparative effectiveness research is increasingly being recognized as a
      method to link research with the information needs of decision makers. As the
      United States begins to invest in comparative effectiveness, it would be wise to
      look at other functioning research networks to understand the infrastructure and
      funding required to support them. METHODS: This case study looks at the
      comparative effectiveness research network in Ontario, Canada, for which a
      neutral coordinating committee is responsible for prioritizing topics, assessing
      evidence, providing recommendations on coverage decisions, and determining
      pertinent research questions for further evaluation. This committee is supported
      by the Medical Advisory Secretariat and several large research institutions. This
      article analyzes the infrastructure and cost needed to support this network and
      offers recommendations for developing policies and methodologies to support
      comparative effectiveness research in the United States. FINDINGS: The research
      network in place in Ontario explicitly links decision making with evidence
      generation, in a transparent, timely, and efficient way. Funding is provided by
      the Ontario government through a reliable and stable funding mechanism that helps
      ensure that the studies it supports are relevant to decision makers. CONCLUSIONS:
      With the recent allocation of funds to support comparative effectiveness research
      from the American Recovery and Reinvestment Act, the United States should begin
      to construct an infrastructure that applies these features to make sure that
      evidence generated from this effort positively affects the quality of health care
      delivered to patients.

PMID- 19751284
TI  - The revolution in health care antitrust: new methods and provocative
      implications.
AB  - CONTEXT: In recent years, federal courts have permitted hospital consolidations
      and other potentially anticompetitive actions by accepting hospitals' claims that
      they compete in expansive geographic markets. Recent events, including two
      actions by the U.S. Federal Trade Commission, suggest that antitrust is
      undergoing a sea change, thanks in part to new methods for defining geographic
      markets. This article reviews the recent history of hospital antitrust, describes
      the methods used to define markets, and illustrates the new methods by
      considering two consolidations recently proposed by a New York regulatory agency.
      METHODS: The new methods for defining geographic markets rely on estimates from
      conditional choice models using patient-level hospitalization data. These
      estimates are the raw material for computations of price effects derived from a
      theoretical model of hospital pricing in a managed care environment. FINDINGS:
      Applying these methods to two proposed consolidations in New York shows that one
      of the mergers would likely raise prices by a substantial amount without the
      promise of offsetting efficiencies but that the other would not have this effect.
      CONCLUSIONS: New methods for geographic market definition may fundamentally alter
      how courts will evaluate antitrust challenges. Although additional research is
      necessary to refine the predictions of these new methods, consolidating
      hospitals, as well as any other hospitals engaging in potentially anticompetitive
      conduct, can no longer anticipate a friendly reception in the courtroom.

PMID- 19751285
TI  - Responsive consumerism: empowerment in markets for health plans.
AB  - CONTEXT: American health policy is increasingly relying on consumerism to improve
      its performance. This article examines a neglected aspect of medical consumerism:
      the extent to which consumers respond to problems with their health plans.
      METHODS: Using a telephone survey of five thousand consumers conducted in 2002,
      this article assesses how frequently consumers voice formal grievances or exit
      from their health plan in response to problems of differing severity. This
      article also examines the potential impact of this responsiveness on both
      individuals and the market. In addition, using cross-group comparisons of means
      and regressions, it looks at how the responses of "empowered" consumers compared
      with those who are "less empowered." FINDINGS: The vast majority of consumers do
      not formally voice their complaints or exit health plans, even in response to
      problems with significant consequences. "Empowered" consumers are only minimally
      more likely to formally voice and no more likely to leave their plan. Moreover,
      given the greater prevalence of trivial problems, consumers are much more likely
      to complain or leave their plans because of problems that are not severe. Greater
      empowerment does not alleviate this. CONCLUSIONS: While much of the attention on
      consumerism has focused on prospective choice, understanding how consumers
      respond to problems is equally, if not more, important. Relying on consumers'
      responses as a means to protect individual consumers or influence the market for
      health plans is unlikely to be successful in its current form.

PMID- 19751286
TI  - Columbia University's Axel patents: technology transfer and implications for the
      Bayh-Dole Act.
AB  - CONTEXT: The Bayh-Dole Act of 1980, which gave federal grantees and contractors
      the right to patent and license inventions stemming from federally funded
      research, was intended to encourage commercial dissemination of research that
      would otherwise languish for want of a patent incentive. The case of Columbia
      University's Axel patents, which claimed a scientific method to introduce foreign
      proteins into nucleated cells, illustrates a secondary outcome of the Bayh-Dole
      Act: the incentive for federal grantees and contractors to pursue royalty
      revenues from patented research, even for inventions for which commercial use did
      not require patents. METHODS: This article describes oral interviews with two of
      the three inventors and a former high-ranking administrator at Columbia;
      correspondence with several faculty members at Columbia to obtain key royalty
      figures and information about Columbia's licensing strategy; patent searches;
      examinations of legal records of court proceedings; and analysis of citation
      trends for the seminal papers disclosing the invention of cotransformation.
      FINDINGS: Columbia University and the inventors profited handsomely from the Axel
      patents, earning $790 million in revenues through licensing arrangements that
      tapped profits from end products made by biotechnology and pharmaceutical
      companies. Columbia's aggressive effort to extend the patent duration also led to
      considerable legal expenditures and fierce controversy. In particular, obtaining
      and enforcing a 2002 patent proved costly, politically difficult, and financially
      fruitless and attracted intense criticism for behavior unbecoming a nonprofit
      academic institution. CONCLUSIONS: This case study raises several important
      questions about the logic and future revisions of the Bayh-Dole Act: Are revenue
      generation and financial rewards for inventing valuable technologies legitimate
      goals for this act? If so, does the federal government need credible mechanisms
      for oversight of, or checks and balances on, the rights conferred?

PMID- 19751288
TI  - Polymerization stress, flow and dentine bond strength of two resin-based root
      canal sealers.
AB  - AIM: To compare two resin-based root canal sealers (AH Plus and dual cure
      Epiphany) in terms of flow, polymerization stress and bond strength to dentine.
      METHODOLOGY: Flow was evaluated by measuring the diameter of uncured discs of
      sealer (0.5 mL) after 7 min compression (20N) between two glass plates (n = 5).
      Polymerization stress was monitored for 60 min in 1-mm thick discs bonded to two
      glass rods (O = 5 mm) attached to a universal testing machine (n = 3). Bond
      strength was analyzed through micropush-out test (n = 10) and failure mode was
      examined with scanning electron microscope (100x and 2500x). Data were
      statistically analyzed using the Student's t-test (alpha = 0.05). RESULTS:
      Polymerization stress was 0.32 +/- 0.07 MPa for Epiphany self-cure, 0.65 +/- 0.08
      MPa for Epiphany light-cure and zero for AH Plus (P < 0.05). Flow data and bond
      strength values were 30.9 +/- 1.1, 28.6 +/- 0.7 mm and 6.3 +/- 5.3, 17.8 +/- 7.5
      MPa for Epiphany and AH Plus, respectively (P < 0.001). Failure mode was
      predominantly cohesive in the sealer for both materials. CONCLUSIONS: Epiphany
      had higher flow and polymerization stress and lower bond strength values to
      dentine than AH Plus. In view of these findings it can be implied that AH Plus
      would provide a better seal.

PMID- 19751289
TI  - Evaluation of the cost-effectiveness of root canal treatment using conventional
      approaches versus replacement with an implant.
AB  - AIM: To evaluate the cost-effectiveness of root canal treatment for a maxillary
      incisor tooth with a pulp infection, in comparison with extraction and
      replacement with a bridge, denture or implant supported restoration. METHODOLOGY:
      A Markov model was built to simulate the lifetime path of restorations placed on
      the maxillary incisor following the initial treatment decision. It was assumed
      that the goal of treatment was the preservation of a fixed platform support for a
      crown without involving the adjacent teeth. Consequently, the model estimates the
      lifetime costs and the total longevity of tooth and implant supported crowns at
      the maxillary incisor site. The model considers the initial treatment decisions,
      and the various subsequent treatment decisions that might be taken if initial
      restorations fail. RESULTS: Root canal treatment extended the life of the tooth
      at an additional cost of pound5-8 per year of tooth life. Provision of orthograde
      re-treatment, if the root canal treatment fails returns further extension of the
      expected life of the tooth at a cost of pound12-15 per year. Surgical re
      treatment is not cost-effective; it is cheaper, per year, to extend the life of
      the crown by replacement with a single implant restoration if orthograde
      endodontic treatment fails. CONCLUSION: Modelling the available clinical and cost
      data indicates that, root canal treatment is highly cost-effective as a first
      line intervention. Orthograde re-treatment is also cost-effective, if a root
      treatment subsequently fails, but surgical re-treatment is not. Implants may have
      a role as a third line intervention if re-treatment fails.

PMID- 19751290
TI  - Long-term sealing ability of Resilon apical root-end fillings.
AB  - AIM: To evaluate ex vivo the long-term sealing ability of the SE Resilon Epiphany
      system as an apical root-end filling material. METHODOLOGY: A total of 60
      standardized horizontal bovine root sections were divided into three groups
      filled with either gutta-percha with AH 26, tooth-coloured mineral trioxide
      aggregate (MTA) or Resilon pellets with Epiphany SE, and submitted to capillary
      flow porometry at 48 h, 1 and 6 months to assess the minimum, mean flow and
      maximum pore diameters. Results of the different materials and results by
      material and time were analysed statistically using nonparametric tests; the
      level of significance was set at 0.05. RESULTS: Resilon had smaller pore
      diameters than gutta-percha and MTA at 48 h and smaller mean flow and maximum
      pore diameters than gutta-percha and MTA at 1 month. At 6 months Resilon had
      larger minimum pore diameters than gutta-percha. Although not always
      statistically significant, the minimum, mean flow and maximum pore diameters of
      gutta-percha and MTA diminished with time. This was not the case for Resilon,
      where the same parameters increased. CONCLUSIONS: All materials leaked at all
      times. Resilon performed better than gutta-percha and MTA in the short-term, but
      the seal of MTA and gutta-percha improved over time whereas the seal of Resilon
      deteriorated. It is critical to evaluate the performance of materials in the long
      term contrary to most studies which are short-term.

PMID- 19751291
TI  - An in vivo experimental model to assess furcal lesions as a result of
      perforation.
AB  - AIM: To design and validate a rat molar model of furcal perforation to allow
      investigation of the biological phenomena that follow and to explore its
      potential for evaluating repair materials under standardized conditions.
      METHODOLOGY: Eighteen male Wistar rats were used. Surgical aseptic procedures
      were carried out in order to open the pulp chamber of a first molar tooth. A
      cavity was prepared on the floor of the pulp chamber using a (1/4) round bur that
      created a communication between the furcation and the periodontal tissues. Six
      animals for each time point were sacrificed on days 14, 21 and 28 to assay
      morphological changes at the furcation region of molars. Maxillary bone was
      processed, removed and sectioned. Cellular infiltration, collagen deposition and
      bone resorption were assessed by histological analysis. Cellularity in the lesion
      area was determined by morphometric analysis. Data were analysed using parametric
      Student's t-test. RESULTS: A furcal perforation model was standardized in which
      both radiological outcome and periodontal tissue reactions could be assessed
      through evaluation of cellularity, osteoclast activity and collagen deposition.
      The morphometric analysis revealed a greater number of cells 21 day post-surgery
      when compared with 14 days. CONCLUSION: This animal model was suitable for
      radiological and histological evaluation of the processes that accompany surgical
      furcal perforation.

PMID- 19751292
TI  - The morphology of the apical foramen in posterior teeth in a North Indian
      population.
AB  - AIM: To determine the position and shape of the apical foramina in posterior
      teeth derived from an Indian population. METHODOLOGY: A total of 800 freshly
      extracted maxillary and mandibular premolar and molar teeth from a native Haryana
      population were collected. Apices of teeth were stained with methylene blue and
      then examined stereomicroscopically (40x). The following observations were made:
      number of apical foramina; size and shape of the minor apical foramen; accessory
      foramina frequency, and deviation of the minor apical foramina (frequency and
      distance) from the apex. RESULTS: The mean maximum and minimum diameter of the
      minor apical foramina ranged from 0.158 to 0.323 mm. The most common minor apical
      foramen shape was oval (81%). Frequency of accessory foramina was between 2% and
      41% for the various tooth types. The frequency of deviation of the minor apical
      foramina from the anatomic apex varied from 43% to 83% and the distance of
      deviation in all the teeth was between 0.052 and 2.921 mm. CONCLUSIONS: The
      incidence of oval canals was higher in this Indian population compared to other
      populations. In 92% and 96% of teeth the difference between the maximum and the
      minimum diameter of all foramina was less than or equal to 0.20 and 0.25 mm,
      respectively. Therefore, four to five instrument sizes larger than the first
      binding file would have been necessary to shape the minor apical foramen of more
      than 95% of the teeth included in this study to make them round.

PMID- 19751293
TI  - Carbon dioxide laser irradiation stimulates mineralization in rat dental pulp
      cells.
AB  - AIM: To examine the effect of carbon dioxide laser irradiation on mineralization
      in dental pulp cells. METHODOLOGY: Rat dental pulp cells were irradiated with a
      carbon dioxide laser at 2 W output power for 20, 40 and 60 s, and were cultured
      in ascorbic acid and beta-glycerophosphate containing media. Cell viability was
      examined 24 h after laser irradiation by a modified MTT assay. Alizarin Red S
      staining was performed 10 days after laser irradiation. The amounts of secreted
      collagen from the cells after irradiation were quantified following Sirius Red
      staining. The expression levels of collagen type I and HSP47, collagen-binding
      stress protein, were analysed by real-time PCR. HSP47 protein expression was
      examined by Western blotting. Statistical analysis was performed using one-way
      analysis of variance (anova) followed by the Tukey's multiple comparison test.
      RESULTS: The cell viability was not affected by laser irradiation at 2 W for up
      to 40 s. However, it was significantly decreased by 20% at 60 s (P < 0.05). The
      amount of mineralization after 10 days of irradiation at 2 W for 40 s was
      significantly increased in comparison to the other conditions (P < 0.05). The
      extracellular collagen production was significantly increased by 73% on day 2 and
      38% on day 4 after laser irradiation (P < 0.05). Although collagen type I gene
      expression was not changed by laser irradiation, HSP47 gene and protein
      expression was induced within 12 and 24 h, respectively. CONCLUSIONS: These
      results suggested that carbon dioxide laser irradiation stimulated mineralization
      in dental pulp cells. The laser irradiation also increased HSP47 expression but
      not collagen gene expression.

PMID- 19751294
TI  - Torsional behaviour of rotary NiTi ProTaper Universal instruments after multiple
      clinical use.
AB  - AIM: To assess the influence of multiple clinical uses on the torsional behaviour
      of ProTaper Universal rotary NiTi instruments. METHODOLOGY: Root canal treatments
      were performed on patients using the ProTaper Universal rotary system to prepare
      canals. Ten sets of instruments were used by an experienced endodontist, each set
      being used in five molar teeth. After clinical use, S1, S2, F1 and F2 instruments
      were analysed for damage by optical and scanning electron microscopy. The used
      sets, along with a control group of 10 sets of new instruments, were then torsion
      tested based on the ISO 3630-1 specification. Data obtained were subjected to a
      one-way analysis of variance (anova) with alpha = 0.05. RESULTS: The use of the
      ProTaper Universal rotary instruments by an experienced endodontist allowed for
      the cleaning and shaping of the root canal system of five molar teeth without
      fracture. The maximum torque for instruments S2, F1 and F2, and the angular
      deflection at fracture for instruments S2 and F1 were significantly lower
      following clinical use. The largest decrease in maximum torque was 18.6% (P =
      0.014) for S2 instruments. The same maximum percent decrease was found for
      angular deflection at fracture for F1 instruments (P = 0.009). CONCLUSIONS:
      Torsional resistance and angular deflection of used instruments, as compared to
      that of new instruments, were reduced following clinical use.

PMID- 19751296
TI  - Epidemiology of primary hyperparathyroidism in Tayside, Scotland, UK.
AB  - OBJECTIVE: To evaluate prevalence and incidence of diagnosed primary
      hyperparathyroidism (PHPT) in adults between 1997 and 2006 in Tayside, Scotland,
      UK. DESIGN: Population-based incidence and prevalence study. PATIENTS: All
      Tayside residents aged 20 years and over with an increased serum calcium level (>
      2.55 mmol/l) between 1997 and 2006 were included as potential participants. Using
      a unique patient identifier, data-linkage enabled a data set of PHPT patients to
      be created from an algorithm of biochemistry records, nuclear scan records,
      histology records, hospital clinic letters and community based prescription
      records. Persons having tertiary hyperparathyroidism (14.0%) were also identified
      and were excluded. OUTCOME MEASURES: Age and sex adjusted incidence density and
      period prevalence were calculated for each year. RESULTS: We identified 2709
      patients (70.8% female) diagnosed with PHPT by the end of 2006. The mean age of
      women (68 years SD = 14) was older than that of men (64 years SD = 15) at
      baseline. The prevalence of diagnosed PHPT in Tayside increased from 1.82 per
      1000 population in 1997 to 6.72 per 1000 population in 2006 (P < 0.001).
      Prevalence of PHPT is higher in females, and the female preponderance increases
      with age; the annual prevalence ratio between women and men is stable at around
      2.5 each year. There was a 3-4-year cyclical incidence rate varying from 4.13 to
      11.30 per 10 000 person-years. CONCLUSION: We observed a general increase in the
      prevalence of diagnosed PHPT in Tayside, Scotland. The incidence of diagnosis is
      greater in females than in males and increases with age. The annual incidence
      followed an apparent cyclic curve during the study period.

PMID- 19751297
TI  - Acute hyperinsulinaemia and hyperlipidaemia modify circulating adiponectin and
      its oligomers.
AB  - OBJECTIVE: Obesity and insulin resistance are associated with low adiponectin
      levels, although adiponectin is exclusively expressed in white adipose tissue.
      The mechanism beyond that paradox is not entirely clear, although insulin itself
      may reduce circulating adiponectin levels. However, obesity is also associated
      with hyperlipidaemia and the effects of free fatty acids (FFAs) and triglycerides
      (TG) on circulating adiponectin levels have not yet been investigated. MATERIALS
      AND METHODS: We analysed the effect of an acute and euglycaemic elevation of
      insulin on adiponectin oligomers in 23 healthy individuals. In a subgroup
      including 11 healthy men, FFAs and TG were acutely elevated by infusion of
      heparin/lipids over 120 min. Again the effect on circulating adiponectin and its
      oligomers was investigated. Adiponectin was determined by ELISA, oligomers were
      detected by nondenaturating Western blot. RESULTS: Acute hyperinsulinaemia
      resulted in a significant reduction of total adiponectin to 7.74 +/- 0.98
      microg/ml (P = 0.004). High molecular weight (HMW) adiponectin did not change
      (0.80 +/- 0.12 to 0.81 +/- 0.14 microg/ml; P = 0.887), whereas MMW adiponectin
      decreased from 4.30 +/- 0.51 to 3.78 +/- 0.48 microg/ml (P = 0.005) and LMW
      adiponectin from 3.63 +/- 0.42 to 3.15 +/- 0.46 microg/ml (P = 0.048).
      Interestingly, heparin/lipid infusion also reduced circulating adiponectin levels
      (P = 0.001), which was primarily the result of reduced MMW adiponectin (P =
      0.004), whereas LMW and HMW were not significantly affected. CONCLUSIONS: The
      presented data suggest that both, hyperinsulinaemia and hyperlipidaemia, may
      contribute to low adiponectin levels in states of obesity.

PMID- 19751298
TI  - A paradoxical difference in relationship between anxiety, depression and thyroid
      function in subjects on and not on T4: findings from the HUNT study.
AB  - OBJECTIVE: There have been conflicting reports on the relationship between
      thyroid function and mood between studies in subjects on T4 and the general
      population not on T4. We investigated this relationship in a large catchment area
      based study. DESIGN: We analysed data on serum TSH levels and Hospital Anxiety
      and Depression Scale (HADS) scores from the HUNT 2 study (age > or = 40 years).
      Following a test for interaction, analyses were performed separately in females
      on T4 (n = 1265) and in people not on T4 (males n = 9319 and females n = 17 694).
      RESULTS: More females on T4 had high depression and anxiety scores than females
      not on T4 (depression 18.4%vs. 13.0%, P < 0.001, anxiety 23.4%vs. 18.7%, P <
      0.001). In those not on T4, there was an inverse association between serum TSH
      and depression score in males (B coefficient = -0.61, 95% CI -0.91 to -0.24, P =
      0.001) though not in females (B coefficient = -0.07, -0.33 to 0.19), and an
      inverse association between TSH and anxiety score in both genders (B coefficient
      for males = 0.68, 95% CI -1.04 to -0.32, P < 0.001; females -0.37, 95% CI -0.67
      to -0.08, P = 0.01). In contrast, in females on T4, TSH was positively associated
      with both depression (B coefficient = +0.27, 95% CI 0.02 to 0.51, P < 0.05) and
      anxiety (B coefficient = +0.29, 95% CI 0.01 to 0.56, P < 0.05). CONCLUSIONS:
      There is a different relationship between thyroid function and depression and
      anxiety in females on T4 compared with individuals with no thyroid disease. This
      group also has a higher prevalence of depression and anxiety.

PMID- 19751306
TI  - Does a unified accreditation system benefit school health education programs?

PMID- 19751307
TI  - Improving the school environment to reduce school violence: a review of the
      literature.
AB  - BACKGROUND: School violence can impact the social, psychological, and physical
      well-being of both students and teachers and disrupt the learning process. This
      review focuses on a new area of research, the mechanisms by which the school
      environment determines the likelihood of school violence. METHODS: A search for
      peer-reviewed articles was made in six databases and the Centers for Disease
      Control and Prevention's report on school-violence interventions. Twenty-five
      articles that attempted to understand the influence of either the school social
      or physical environment in determining teacher and student perceptions of safety
      and experiences of violence were included. RESULTS: Most of the included articles
      were cross-sectional surveys of junior high or high school students and staff. As
      articles used different measures of the school physical and social environment, a
      classification system was created. Using this system, studies show that schools
      with less violence tend to have students who are aware of school rules and
      believe they are fair, have positive relationships with their teachers, feel that
      they have ownership in their school, feel that they are in a classroom and school
      environment that is positive and focused on learning, and in an environment that
      is orderly. CONCLUSION: The school social and physical environment appears to
      offer intervention opportunities to reduce school violence. However, the lack of
      consistency in school environment variables as well as the lack of longitudinal
      and experimental research designs limits the applicability of these findings.

PMID- 19751308
TI  - A comparison of weight-related behaviors among high school students who are
      homeless and non-homeless.
AB  - BACKGROUND: Previous research has shown that youth who are homeless engage in
      high-risk behaviors. However, there has been little information published on
      nutritional and physical activity behaviors in this population, and studies
      comparing homeless youth in school with their non-homeless peers are scarce. This
      study compares weight-related risk behaviors of public high school students in
      Massachusetts based on homeless status. METHODS: We obtained data from 3264 9th
      through 12th grade students who participated in the 2005 Massachusetts Youth Risk
      Behavior Survey. Multivariable logistic regression, controlling for gender,
      grade, race/ethnicity, and sexual orientation, was performed to assess the
      relationship between homeless status as defined by the McKinney-Vento Homeless
      Assistance Act and weight-related indicators. Analyses were weighted and adjusted
      for the multistage complex sampling design. RESULTS: Of this sample, 4.2%
      reported being homeless (n = 152). Higher prevalence of homelessness was found
      among males, racial/ethnic minorities, sexual minorities, and students who were
      not in a traditional grade level. The distribution of body mass index was similar
      among students who were homeless and non-homeless (underweight 4.0 and 3.0%, and
      overweight 27.1 and 27.1%, respectively). Homeless students were more likely than
      non-homeless students to report disordered weight-control behaviors including
      fasting (aOR 2.5, 95% CI 1.4-4.5) and diet pill use (aOR 3.3, 95% CI 1.6-6.9).
      CONCLUSIONS: More than 4% of public high school students in Massachusetts meet
      the federal definition of homelessness. These students are at high risk for
      disordered weight-control behaviors. Policy decisions at the school, state, and
      federal levels should make a concerted effort to target these students with
      social services and nutritional interventions.

PMID- 19751309
TI  - Changes in psychosocial factors and physical activity frequency among third- to
      eighth-grade girls who participated in a developmentally focused youth sport
      program: a preliminary study.
AB  - BACKGROUND: Despite the numerous physiological, psychological, and academic
      benefits of physical activity (PA), declines in PA levels among girls have been
      observed over the last decade. The purpose of this preliminary study was to
      assess the short-term changes pertaining to Girls on the Run and Girls on Track
      developmentally focused youth sport programs (DYS) on global self-esteem, body
      image, commitment to PA, and PA frequency. METHODS: This preliminary study
      employed a nonexperimental, one-group, pre- and postintervention study design
      using a 29-item paper-and-pencil assessment tool (n = 1034). RESULTS: Paired
      sample t-tests from pre- to postintervention revealed statistically significant
      differences in self-esteem (p < .001), body size satisfaction (p < .001), and
      vigorous PA frequency (p < .001). Stratification by the number of times
      participating in the intervention revealed the greatest changes at first
      participation followed with continued improvements in self-esteem (p = .013) and
      body size satisfaction (p < .001) for those participating in a second time. Age
      differences were also observed between participants </=10 years old and 11-15
      years; in that significant improvements in commitment to PA (p = .003) were
      observed for the older girls. CONCLUSIONS: Findings suggest DYS programs Girls on
      the Run and Girls on Track may produce beneficial changes in self-esteem, body
      size satisfaction, PA commitment, and PA frequency. Although the findings from
      the current report are preliminary, they suggest that DYS programs designed
      exclusively for girls may provide the necessary framework to promote PA to
      achieve the numerous associated benefits.

PMID- 19751310
TI  - Participation in the national school lunch program: importance of school-level
      and neighborhood contextual factors.
AB  - BACKGROUND: This study examined the effect of stigma (proxied by school-level
      peer participation), neighborhood food environment, and demographic
      characteristics on participation in the U.S. Department of Agriculture National
      School Lunch Program (NSLP). METHODS: The 1997 and 2003 waves of the Child
      Development Supplement to the Panel Study of Income Dynamics were linked to
      external data on school-level free lunch eligibility rate, fast food restaurant
      availability in the school zip code, and food store availability and neighborhood
      socioeconomic status in the home zip code. Probit models examined the effects of
      contextual and demographic factors on NSLP participation and free/reduced-price
      NSLP participation, conditional on eligibility. Differences were analyzed by
      grade. RESULTS: A 10% higher free lunch eligibility rate in a child's school was
      associated with a 1.8 percentage point increase in the probability of NSLP
      participation and 2.6 and 6.7 percentage points increase in free/reduced-price
      NSLP participation among all and high school eligible student, respectively.
      Fewer grocery stores and more convenience stores increased NSLP participation.
      Fast food restaurant availability in the school neighborhood decreased
      free/reduced-price NSLP participation for high school students only. The addition
      of the contextual factors reduced the estimated association with several of the
      demographic covariates, especially race. CONCLUSIONS: The significant positive
      association between NLSP participation and school-level free lunch eligibility,
      especially for the free/reduced-price NSLP participation, suggested that stigma,
      or possibly peers, affected participation. Neighborhood and school contextual
      variables had significant effects on school lunch take-up and the results
      differed between high school and elementary/middle school students.

PMID- 19751311
TI  - Evaluating the strength of school tobacco policies: the development of a
      practical rating system.
AB  - BACKGROUND: School tobacco control policies vary widely in their strength,
      extensiveness, and enforcement. Currently, no standardized method exists to
      assess the comprehensiveness of school tobacco policies. The purpose of this
      study was to develop a new practical rating system for school tobacco policies,
      assess its reliability, and present preliminary validation data. METHODS: This
      study presents the systematic development of a rating system to assess the
      strength of school tobacco policies. Based on the empirical literature and the
      expertise of an advisory panel consisting of educational leaders and tobacco
      control advocates and practitioners, a "gold standard" school tobacco policy was
      developed and guided the content of the 40-point rating system. The 4 domains of
      the School Tobacco Policy Index were: Tobacco-free environment (14 points),
      Enforcement (12 points), Prevention and treatment services (6 points), and Policy
      organization (8 points). RESULTS: The Index was pilot-tested using 95 Missouri
      public school district tobacco policies and proved to be highly reliable among
      coders. The evaluated policies varied greatly between school districts, with the
      lowest total policy score of phi and the highest score of 21. School district
      policy scores were significantly related to a number of county-level tobacco
      policy characteristics, including support for a tobacco excise tax increase.
      CONCLUSIONS: The Index is a user-friendly, practical tool for tobacco control
      professionals and educators, providing them with the ability to easily evaluate
      their own school policies. Their evaluation efforts will be useful in
      strengthening existing policies and developing new comprehensive policies to
      protect the health of students, staff, administrators, and visitors.

PMID- 19751312
TI  - Relationship building blocks.

PMID- 19751313
TI  - New tricks for old dogs: KCNQ expression and role in smooth muscle.
AB  - Ion channels encoded by the KCNQ gene family (K(v)7.1-7.5) are major determinants
      of neuronal membrane potential and the cardiac action potential. This key
      physiological role is highlighted by the existence of a number of hereditary
      disorders caused by mutations to KCNQ genes. Recently, KCNQ gene expression has
      been identified in vascular and non-vascular smooth muscles. In addition,
      experiments with an array of pharmacological modulators of KCNQ channels have
      supported a crucial role for these channels in regulating smooth muscle
      contractility. This article will provide an overview of present understanding in
      this nascent area of KCNQ research and will offer guidance as to future
      directions.

PMID- 19751314
TI  - Statins and fibrate target ClC-1 - from side effects to CLC pharmacology.
AB  - Lipid-lowering drugs have been associated with severe adverse effects on skeletal
      muscle, including rhabdomyolysis. More common symptoms include cramps and
      myalgia. In this issue of the BJP, Pierno et al. find that two statins and
      fenofibrate, often used in combination, decrease function of the chloride channel
      member 1 of the mammalian CLC protein family of chloride channels and
      transporters in skeletal muscle by three distinct mechanisms. Other compounds
      have recently been shown to potently modulate the pharmacologically less well
      explored CLC protein family, which comprises chloride channels and
      chloride/proton antiporters. These findings may well lead to a new era of CLC
      protein pharmacology.

PMID- 19751315
TI  - Ezetimibe - new anti-atherogenic properties?
AB  - Ezetimibe, a Niemann Pick C1-like1 inhibitor, inhibits cholesterol absorption.
      The drug has been shown to affect lipid raft function in monocytes and therefore
      may inhibit lipid accumulation in the atheromatous plaque with a mechanism that
      is unrelated to its effect in reducing cholesterol absorption. In this issue of
      the British journal of pharmacology, Gomez-Garre et al. demonstrate that
      ezetimibe and simvastatin both have a beneficial effect on the atheromatous
      plaque, which may be due to their effect on both monocyte/macrophage function and
      reduction in nuclear factor-kappaB activity. Whether these results in a rabbit
      model of atherosclerosis can be translated into human atherosclerosis awaits
      further studies.

PMID- 19751317
TI  - Abstracts of the 14th Congress of the International Headache Society. September
      10-13, 2009. Philadelphia, Pennsylvania, USA.

PMID- 19751316
TI  - Biochemical and behavioural characterization of EMPA, a novel high-affinity,
      selective antagonist for the OX(2) receptor.
AB  - BACKGROUND AND PURPOSE: The OX(2) receptor is a G-protein-coupled receptor that
      is abundantly found in the tuberomammillary nucleus, an important site for the
      regulation of the sleep-wake state. Herein, we describe the in vitro and in vivo
      properties of a selective OX(2) receptor antagonist, N-ethyl-2-[(6-methoxy
      pyridin-3-yl)-(toluene-2-sulphonyl)-amino]-N-pyridin-3-ylmethyl-acetamide (EMPA).
      EXPERIMENTAL APPROACH: The affinity of [(3)H]EMPA was assessed in membranes from
      HEK293-hOX(2)-cells using saturation and binding kinetics. The antagonist
      properties of EMPA were determined by Schild analysis using the orexin-A- or
      orexin-B-induced accumulation of [(3)H]inositol phosphates (IP). Quantitative
      autoradiography was used to determine the distribution and abundance of OX(2)
      receptors in rat brain. The in vivo activity of EMPA was assessed by reversal of
      [Ala(11),D-Leu(15)]orexin-B-induced hyperlocomotion during the resting phase in
      mice and the reduction of spontaneous locomotor activity (LMA) during the active
      phase in rats. KEY RESULTS: [(3)H]EMPA bound to human and rat OX(2)-HEK293
      membranes with K(D) values of 1.1 and 1.4 nmol x L(-1) respectively. EMPA
      competitively antagonized orexin-A- and orexin-B-evoked accumulation of [(3)H]IP
      at hOX(2) receptors with pA(2) values of 8.6 and 8.8 respectively.
      Autoradiography of rat brain confirmed the selectivity of [(3)H]EMPA for OX(2)
      receptors. EMPA significantly reversed [Ala(11),D-Leu(15)]orexin-B-induced
      hyperlocomotion dose-dependently during the resting phase in mice. EMPA, injected
      i.p. in rats during the active phase, reduced LMA dose-dependently. EMPA did not
      impair performance of rats in the rotarod procedure. CONCLUSIONS AND
      IMPLICATIONS: EMPA is a high-affinity, reversible and selective OX(2) receptor
      antagonist, active in vivo, which should prove useful for analysis of OX(2)
      receptor function.

PMID- 19751318
TI  - Recurrent pregnancy loss: a disease of inflammation and coagulation.
AB  - Recurrent pregnancy loss (RPL) is one of the most common obstetrical
      complications. Multiple etiologies, such as endocrine, anatomic, genetic,
      hematological and immunological causes have been reported for this devastating
      disease. However, over half of the cases remain unexplained.
      Thrombotic/inflammatory processes are often observed at the maternal-fetal
      interface as the final pathological assault in many cases of RPL, including those
      of unexplained etiologies. In the present paper, cellular immune responses (T,
      natural killer [NK], natural killer-T [NKT], regulatory T [Treg] cells and their
      cytokines) and autoimmune abnormalities of women with RPL are reviewed. In
      addition, metabolic diseases and hematological conditions which often lead to
      thrombotic/inflammatory conditions are discussed in association with RPL.
      Finally, current therapeutic options for RPL are reviewed.

PMID- 19751319
TI  - Fetal arrhythmia: prenatal diagnosis and perinatal management.
AB  - The importance of managing fetal arrhythmia has increased over the past three
      decades. Although most fetal arrhythmias are benign, some types cause fetal
      hydrops and can lead to fetal death. With the aim of improving the outcome in
      such cases, various studies for prenatal diagnosis and perinatal management have
      been published. Detailed analysis of the type of arrhythmia in utero is possible
      using M-mode and Doppler echocardiography. In particular, a simultaneous record
      of Doppler waveform at the superior venous cava and the ascending aorta has
      become an important and useful method of assessing the interval between atrial
      and ventricular contractions. Common causes of fetal tachycardia (ventricular
      heart rate faster than 180 bpm), are paroxysmal supraventricular tachycardia
      (SVT) with 1:1 atrioventricular (AV) relation and atrial flutter with 2:1 AV
      relation. Of fetal SVT, short ventriculo-atrial (VA) interval tachycardia due to
      atrioventricular reentrant tachycardia is more common than long VA interval. Most
      fetuses with tachycardia are successfully treated in utero by transplacental
      administration of antiarrhythmic drugs. Digoxin is widely accepted as a first
      line antiarrhythmic drug. Sotalol, flecainide and amiodarone are used as second
      line drugs when digoxin fails to achieve conversion to sinus rhythm. Fetal
      bradycardia is diagnosed when the fetal ventricular heart rate is slower than 100
      bpm, mainly due to AV block. Approximately half of all cases are caused by
      associated congenital heart disease, and the remaining cases that have normal
      cardiac structure are often caused by maternal SS-A antibody. The efficacy of
      prenatal treatment for fetal AV block is limited compared with treatment for
      fetal tachycardia. Beta stimulants and steroids have been reported as effective
      transplacental treatments for fetal AV block. Perinatal management based on
      prospective clinical study protocol rather than individual experience is crucial
      for further improvement of outcome in fetuses with tachycardia and bradycardia.

PMID- 19751320
TI  - Vaccinium macrocarpon: an interesting option for women with recurrent urinary
      tract infections and other health benefits.
AB  - AIM: To review the scientific publications concerning the clinical use and
      mechanism of action of the North American cranberry (Vaccinium macrocarpon) for
      women with recurrent urinary tract infections (UTI) and other health conditions.
      METHODS: This is a retrospective study of published information concerning
      Vaccinium macrocarpon retrieved from a PubMed and individual searches. RESULTS:
      Urinary tract infections are very common in women, cause discomfort, and may
      aggravate other genitourinary conditions. The available scientific information
      supports a clinical benefit of Vaccinium macrocarpon in the prevention of
      recurrent UTI in women. There is a non-significant reduction of UTI associated
      with Vaccinium macrocarpon treatment during pregnancy. A group of
      proanthocyanidins (PAC) with A-type linkages have been isolated from Vaccinium
      macrocarpon which inhibit P-fimbriae synthesis and induce a bacterial
      deformation, on both antibiotic-susceptible and antibiotic-resistant
      uropathogenic Escherichia coli. It is plausible that cranberry PAC prevent
      bacteria from adhering to the uroepithelium of the bladder, thereby blocking the
      ability of E. coli to infect the urinary mucosa. CONCLUSION: Cranberry treatment
      is a safe, well-tolerated supplement that does not have significant drug
      interactions. Although investigations are in the early stages, experimental and
      preclinical studies suggest that cranberry components may have other potential
      benefits, including anti-infective, anticancer and antioxidant effects, which may
      be considered as positive for different age-related conditions. In addition,
      cranberry components may induce positive cardiovascular and metabolic changes,
      and may improve neuropsychological activity. These effects warrant further
      clinical research to better place the role of cranberry products for women.

PMID- 19751321
TI  - Modified sequential laser photocoagulation of placental communicating vessels for
      twin-twin transfusion syndrome to prevent fetal demise of the donor twin.
AB  - AIMS: Twin-twin transfusion syndrome (TTTS) complicated with absent or reversed
      end-diastolic flow in the umbilical artery (UA-AREDF) of the donor has a high
      perinatal mortality rate. To improve the prenatal outcome, we introduced and
      modified the technique of sequential selective laser photocoagulation of
      communicating vessels (SQLPCV), and assessed the clinical efficacy. METHODS: The
      modified SQLPCV was designed with the following order of coagulation: (i) artery
      to-artery (AA) anastomoses; (ii) venous-to-venous anastomoses; (iii) artery-to
      venous anastomoses from donor to recipient; and (iv) artery-to-venous anastomoses
      from recipient to donor. TTTS patients with UA-AREDF of donors were recruited,
      and the perinatal outcome and its association with the types of anastomoses were
      compared in patients who underwent the standard selective laser method (SLPCV).
      RESULTS: Twenty-three patients underwent modified SQLPCV and 29 underwent SLPCV.
      Total intrauterine fetal death (IUFD) was significantly lower in modified SQLPCV
      than in SLPCV (9% vs 38%; P < 0.001). Donor IUFD was significantly lower in
      modified SQLPCV than in SLPCV (13% vs 52%; P = 0.007); however, no significant
      effect was noted in the recipient IUFD cases. When AA anastomoses were present,
      donor IUFD was significantly lower in modified SQLPCV than it was in SLPCV (18%
      vs 71%; P = 0.018); however, the difference was not significant when AA
      anastomoses were not present (8% vs 25%; P = 0.59). Logistic regression analysis
      revealed that modified SQLPCV served as the protective factor against the donor's
      IUFD (odds ratio = 0.015; 95% confidence interval [0.0001-0.775]; P = 0.037).
      CONCLUSION: The modified SQLPCV was useful for the prevention of the donor's IUFD
      in cases of TTTS with UA-AREDF.

PMID- 19751322
TI  - Analysis of placenta vascularization in patients with uterine altered artery
      Doppler flow velocity exams.
AB  - BACKGROUND: One of the frequent questions in obstetric practice is to determine
      placental vascular changes that may account for abnormal Doppler flow velocity
      alterations in maternal uterine vessels from women and fetuses without pregnancy
      pathology. METHODS: A retrospective morphometric study was realized using 27
      placentas from patients submitted for Doppler flow velocity exam during
      pregnancy. The placentas were morphologically examined using hematoxylin-eosin
      staining. Measurements of villi were made with the use of a video camera coupled
      to a common light microscope and a computer with automatic image analyzing
      software. RESULTS: Of the 27 placentas, 13 (48%) were of patients showing
      unaltered Doppler and 14 (52%) showing altered Doppler. The number of stem villi
      vessels was significantly larger in the placentas of patients with Doppler exam
      alterations (P = 0.003). This group also presented greater stem villi vessel
      thickness, although without significant difference. The number of intermediary
      and terminal villi vessels was greater in the placentas of patients with altered
      Doppler exams (P < 0.001), and a greater terminal villi area was observed in
      these cases (P < 0.001). CONCLUSION: The morphological proof that uterine artery
      Doppler flow velocity exam alterations are associated with placental vascular
      alterations demonstrates the importance of this exam during prenatal care, even
      in the absence of maternal-fetal alterations.

PMID- 19751323
TI  - Relations between fetal head descent and cervical dilatation during individual
      uterine contractions in the active stage of labor.
AB  - The relationship between instantaneous changes in fetal head station and cervical
      dilatation within the individual contraction during the active stage of labor
      were studied and an index of labor progress was suggested. Cervix dilatation and
      fetal head station were measured continuously in 30 nullipara women (mean age
      27.5, standard deviation 4.8). The continuous measurements enabled the analysis
      of each variable and the analysis of the relations between these two variables.
      The relationship between the head station and the cervical dilatation were
      demonstrated by plotting one against the other during a contraction. This led to
      the definition of a contraction vector that integrates the interaction between
      the two variables. The angle of this vector, that indicates this relation, was
      plotted against mean head station to demonstrate change along the delivery
      process regardless of time to normalize the progress and allow comparison between
      different women with different labor durations. This plot showed a sharp change
      from almost zero into a steep curve at about zero head station. A zero angle
      indicates that the cervix dilates during a contraction with little effect on head
      station while a steep angle indicates a significant effect of cervical dilatation
      on head station during the contraction. The contraction-vector angle reflects the
      changing intra-contraction relationship between head station and cervical
      dilatation. The angle of this vector may serve as an indicator of labor progress.

PMID- 19751324
TI  - Pseudocyesis in a rural southeast Nigerian community.
AB  - CONTEXT: Pseudocyesis is uncommon and probably under reported among the African
      population. AIMS AND OBJECTIVES: To document the incidence and presentation of
      false pregnancies in a Nigerian rural population. METHODS: This involved a review
      of prospectively collected data on all patients who were diagnosed with
      pseudocyesis over a four-year period in a Mission hospital. RESULTS: Pseudocyesis
      occurred at a frequency of 1 in 344 pregnancies. The mean age was 33.6 years and
      the condition was found more commonly among poorly educated women. Amenorrhea was
      common among the subjects and 54% claimed they felt fetal movement. Ultrasound
      studies confirmed the absence of pregnancies in all cases. Management included
      counseling and referral to specialist clinical psychologists. CONCLUSION:
      Pseudocyesis is more common among the African population than in developed
      countries. Gynaecologists in these regions should have a high index of suspicion
      to diagnose this and assess the mental status of the subject and the
      precipitating factors.

PMID- 19751325
TI  - Effectiveness of double cervical cerclage in women with at least one previous
      pregnancy loss in the second trimester: a randomized controlled trial.
AB  - AIM: To evaluate the effect of double cervical cerclage on the prevention of
      preterm delivery, and perinatal and maternal outcomes in women with previous
      fetal loss in the second trimester. METHODS: Between January 2001 and December
      2006 we conducted a prospective study in which patients with a previous preterm
      delivery at the second trimester who met clinical criteria for the diagnosis of
      cervical incompetence were randomly allocated to receive double cervical cerclage
      or traditional single cervical cerclage at a ratio of 1:2. RESULTS: The perinatal
      and maternal outcomes of the two groups were compared. A total of 17 women were
      allocated to the double cervical cerclage group, and 34 to the traditional single
      cervical cerclage group. The single cervical cerclage group had a higher
      incidence of preterm delivery at <28 weeks than the double cerclage group (29.4
      vs 5.9%, respectively, P = 0.0528). The mean gestational age and birth weight in
      the double cervical cerclage group were significantly higher than in the
      traditional single cervical cerclage group (35.9 +/- 5.4 vs 32.9 +/- 7.5 weeks,
      respectively for gestational age, P = 0.045; 2696 +/- 911 vs 2242 +/- 1119 g,
      respectively for birth weight, P = 0.048). No significant differences in rates of
      neonatal survival (P = 0.241) and neonatal admission to the intensive care unit
      were found between the two groups. CONCLUSION: Our results demonstrated that
      double cervical cerclage may significantly improve perinatal outcome in women
      with at least one previous pregnancy loss in the second trimester.

PMID- 19751326
TI  - Duration of the second stage of labor while wearing a dental support device: a
      pilot study.
AB  - AIM: Developing a method of maximizing maternal expulsive effort should be of
      great value in reducing the number of cesarean sections or instrumental
      deliveries. Various investigations have shown that use of a dental support device
      (DSD) increases the isometric strength of different muscle groups. The aim of our
      study was to investigate the role of a DSD in second stage of pushing. METHODS:
      Nulliparous women with an uncomplicated singleton pregnancy course were randomly
      assigned either to a DSD group or to a non-device group. Duration of the second
      stage of labor was evaluated. Rates of cesarean section or instrumental delivery
      indicated for failure to descend in the second stage of labor were also
      evaluated. Satisfaction scores for the DSD group were evaluated (range 1-5).
      RESULTS: Sixty-four subjects were enrolled in the study. Cesarean section and
      instrumental delivery were performed for 12 (18.8%) and 5 (7.8%) patients,
      respectively. There was no difference in obstetrical and neonatal demographics
      between the two groups. Among 64 enrolled patients, 38 (59.3%) were evaluated for
      the second stage of labor (n = 19 for each group). Duration of the second stage
      of labor in the DSD group was significantly shorter than in the non-device group:
      (median 19 min (interquartile interval, IQI, 9) vs 31 min (IQI, 23)), P < 0.001.
      One patient in the non-device group required a vacuum extraction for failure to
      descend. The mode of satisfaction score for the DSD group was 5 (59.3%).
      CONCLUSION: Wearing a dental support device may shorten the second stage of
      labor, and may decrease the number of failures to descend requiring operative
      intervention. CLINICAL TRIAL REGISTRATION: NCT00629369.

PMID- 19751327
TI  - Outcome of cesarean section in asymptomatic HIV-1 infection in Kampala, Uganda.
AB  - AIM: Sepsis remains a major cause of morbidity and mortality in Mulago Hospital,
      Kampala, Uganda, following cesarean section (CS). The present study was designed
      to assess whether asymptomatic HIV infection could be contributing to the
      increased morbidity following emergency CS in the form of wound and genital tract
      infection (GTI) with consequent prolonged stay in the hospital. METHODS: Five
      hundred patients who had undergone emergency lower segment CS had their blood
      taken to check for HIV-1 serostatus on the first postoperative day. The patients
      were followed up for evidence of wound sepsis, defined as occult pus discharge on
      compression of the wound or removal of the closing stitches, GTI and duration of
      stay in the hospital after the operation. RESULTS: There were 98 (20.5%) HIV-1
      seropositive patients. The incidence of postoperative wound sepsis (P = 0.948,
      95% confidence interval [CI] 0.56-1.86), GTI (P = 0.339, 95% CI = 0.74-2.39) as
      well as hospital stay >8 days (P = 0.327, 0.78-2.09) was not statistically
      significantly different between the infected and non-infected groups. Significant
      predisposing factors to postoperative morbidity were poor general condition on
      admission, dehydration, preoperative clinical anemia, and ruptured membranes
      prior to the operation. CONCLUSION: Asymptomatic HIV-1 was not associated with
      increased postoperative morbidity following emergency lower segment cesarean
      section.

PMID- 19751328
TI  - Evaluation of D-dimer during pregnancy.
AB  - AIM: The purpose of the present study was to elucidate the change of D-dimer and
      the possibility of deep vein thrombosis screening by D-dimer during pregnancy.
      METHODS: One thousand, one hundred and thirty-one pregnant women were enrolled in
      the study from April 2006 to March 2007. D-dimer was measured by latex
      immunoassay at 6 to 14 and 30 to 36 weeks of gestation, respectively, and the
      veins of the lower extremities were examined by ultrasound at 30 to 36 weeks of
      gestation. RESULTS: The mean and standard error of D-dimer was 1.1 +/- 1.0
      microg/mL in the first trimester and 2.2 +/- 1.1 microg/mL in the third
      trimester, and both values were significantly higher than adult values. In
      addition, D-dimer significantly increased during pregnancy. D-dimer was not
      significantly different between singleton and twin pregnancies in the first
      trimester, but in the third trimester, the values of twin pregnancies were higher
      than singleton pregnancies (2.2 +/- 1.6 vs 3.7 +/- 2.5 microg/mL). The mean value
      of D-dimer of ultrasonographically positive women was 2.6 +/- 2.0 microg/mL,
      which was significantly higher than the value for negative woman during the third
      trimester (2.2 +/- 1.6 microg/mL). The positive predictive value was 7.4% and
      negative predictive value was 95.5% for ultrasonographically positive women when
      D-dimer was set at 3.2 microg/mL. CONCLUSION: We clearly found a change of D
      dimer during pregnancy. When D-dimer was higher than 3.2 microg/mL, the
      percentage of ultrasonographically positive women was high. We propose that women
      with D-dimer higher than 3.2 microg/mL are closely monitored for prevention of
      pulmonary thromboembolism.

PMID- 19751329
TI  - Neonatal C-reactive protein value in prediction of outcome of preterm premature
      rupture of membranes: comparison of singleton and twin pregnancies.
AB  - AIM: The clinical importance of preterm premature rupture of the membranes
      (PPROM) is its relationship to maternal and neonatal mortality and morbidity,
      especially in twin pregnancies. The aim of this study was to determine and
      compare the role of inflammatory factors as predictors of the PPROM outcome
      between singleton and twin pregnancies. METHODS: The medical records of 22 twins
      delivered between 28 and 34 weeks and complicated by PPROM were reviewed at the
      Al-Zahra Hospital in Tabriz, Iran. Also among singletons, 55 cases of matched
      gestational age were randomly selected as a control group. Three laboratory
      indices of neonatal white blood cell (WBC) count and C-reactive protein (CRP) in
      the two groups were measured immediately after delivery and the effects of two
      factors on neonatal outcome were assessed. RESULTS: In singletons, there was
      adverse relationship between the mean of WBC count and duration of latency (P =
      0.007). Also, a positive relationship between the means of ventilation time and
      WBC count in second twins was found (P = 0.034). Positive CRP was the main
      predictor of neonatal intensive care unit admission in both singletons (odds
      ratio: 4.929, P = 0.042) and first twins (odds ratio: 9.000, P = 0.005). However,
      positive CRP did not influence the existence of metabolic acidosis or duration of
      latency in either of the two groups. CONCLUSION: Neonatal WBC count was a
      predictor for the duration of latency in singletons and for ventilation time in
      twins. Positive neonatal CRP was an important factor for the prediction of
      neonatal intensive care unit admission in both types of pregnancy; its role in
      twins is clearer than in singletons.

PMID- 19751330
TI  - Impact of surgeon and hospital volumes on short-term postoperative complications
      after radical hysterectomy for cervical cancer.
AB  - AIM: The association between provider caseload volumes and patient outcomes
      remains unclear in gynecologic cancer surgery, especially with regard to radical
      hysterectomies. The present study aims to clarify the effect of provider volumes
      on short-term postoperative complications after radical hysterectomy for cervical
      cancer. METHODS: We conducted a multicenter study of cervical cancer patients
      undergoing radical hysterectomy in Japan from October 1, 2006 to February 28,
      2007, by collecting medical record-based data on each patient's background,
      operating time and postoperative complications, as well as hospital/surgeon
      volumes. Multivariate analyses were performed to examine the effect of
      hospital/surgeon volumes on operating time and postoperative complications, with
      adjustments for possible confounders. RESULTS: We collected 407 cases from 84
      hospitals around Japan. Higher surgeon volume (> or =200 procedures) was
      associated with shorter operating times (odds ratio [OR], 0.37; 95% confidence
      interval [CI], 0.16-0.86; P = 0.02) and reduced incidence of postoperative
      urinary disorders (OR, 0.45; 95% CI, 0.21-0.96; P = 0.04). Hospital volume was
      not an independent predictor of any of the outcomes. CONCLUSION: Our results
      indicate that the rate of postoperative urinary disorders may be a possible
      benchmark that reflects a surgeon's skill in radical hysterectomy. Thus, high
      surgeon volume may be a proxy for high quality of care; practice could indeed
      make perfect in this clinical setting.

PMID- 19751331
TI  - High-risk human papillomavirus testing for monitoring patients treated for high
      grade cervical intraepithelial neoplasia.
AB  - AIM: The aim of the present study was to examine the accuracy of high-risk human
      papillomavirus (HR-HPV) DNA detection as a predictor of residual or recurrent
      cervical intraepithelial neoplasia (CIN) after treatment of high-grade CIN.
      METHODS: Ninety-five women treated by conization and loop electrosurgical
      excision procedure (LEEP) for high-grade CIN were followed-up with HR-HPV DNA
      testing (Hybrid Capture II test, Digene Diagnostics, Gaithersburg, MD, USA) and
      cytology at 3, 6, 12, 18 and 24 months after treatment. The outcome of our study
      was to detect the presence of CIN using colposcopy-directed biopsy within 24
      months after treatment. RESULTS: Women with recurrent or residual disease did not
      differ from women who were cured within clinicopathologic parameters at
      treatment. Pre-treatment HR-HPV testing was positive in all cases. In the
      recurrent pre-treatment group HR-HPV loads were significantly higher than in the
      group with no recurrence (1065.5 +/- 852.3 vs 527.7 +/- 669.6, P = 0.003).
      Residual or recurrent disease was identified in 17 patients (17.9%) during a 24
      month period. A Pap smear significantly predicted disease recurrence at the first
      follow-up visit only. At the 6-month visit, HR-HPV testing showed 100%
      sensitivity and negative predictive value (NPV). When both a Pap smear and a HR
      HPV test were used together, 82% sensitivity, 76% specificity and 95% NPV was
      noted. Performance of resection margins (odds ratio (OR) 9.8; 95% confidence
      interval (CI), 3.0-32.7) and post-treatment HR-HPV load >100 RLU (OR 9.3; 95% CI,
      2.2-38.2) were also significant. CONCLUSION: HR-HPV testing in conjunction with
      Pap smear offers clear advantages over single cytology when monitoring women
      treated for high-grade CIN.

PMID- 19751332
TI  - HPV vaccination in women over 25 years of age: Asian Cervical Cancer Prevention
      Advisory Board recommendations.
AB  - Cervical cancer is the second most common cancer among women worldwide and is
      responsible for more than 270 000 deaths every year, the majority of which occur
      in Asia. The Asian Cervical Cancer Prevention Advisory Board (ACCPAB) was
      established in 2005 with a mission to raise awareness of the significant disease
      burden of cervical cancer in Asia and the strategies for its prevention.
      Persistent infection with oncogenic subtypes of human papillomavirus (HPV) is the
      necessary cause of cervical cancer. Vaccines against the two most carcinogenic
      subtypes of HPV (HPV 16 and 18) are available and have the potential to prevent
      cervical cancer in 70-80% of HPV- naive women. HPV vaccines have been first
      licensed for use in girls and women aged 9-26 years. However, women over 25 years
      of age are also vulnerable to HPV infection and are likely to benefit from
      vaccination. Current evidence shows that even women previously infected with HPV
      who have subsequently cleared the infection can obtain complete protection
      against the HPV types contained in the vaccines. Therefore, vaccinating sexually
      active women aged over 25 years offers significant benefits and may be expected
      to decrease the incidence of cervical cancer. The ACCPAB advocates the adoption
      of preventive measures against HPV infection, including vaccination, with a view
      to protecting women of all ages from developing cervical cancer.

PMID- 19751333
TI  - Ratio of directly necrotized volume to total volume of a submucosal myoma
      predicts shrinkage after microwave endometrial ablation.
AB  - AIM: To explore parameters relating to shrinkage of submucosal myomas after
      microwave endometrial ablation. METHODS: Fourteen patients underwent microwave
      endometrial ablation at 2.45 GHz using a curved microwave applicator to treat
      menorrhagia caused by a submucosal myoma. The size of myomas was measured on
      magnetic resonance images before, one month after, and six months after the
      operation. The average radius r was defined as half of the size of the myoma
      measured in three dimensions. The protrusion ratio alpha was defined as the ratio
      of the thickness of the protruding part of a myoma in the uterine cavity to the
      size of the myoma before the operation. The ratio of the directly necrotized
      volume by microwave irradiation to the total volume (RODNeV) of preoperative
      myomas was calculated using the following formula: (1) where d is the depth of
      myoma tissue directly necrotized by microwave irradiation. The relationships of
      preoperative alpha, r and RODNeV to postoperative shrinkage were then examined.
      RESULTS: Two-dimensional plots showing shrinkage of submucosal myomas versus the
      RODNeV indicated that shrinkage at six months after microwave endometrial
      ablation depends on the RODNeV. Myomas with a RODNeV greater than 0.17 had shrunk
      more than 50% at six months after the operation. CONCLUSIONS: RODNeV is closely
      related to postoperative necrosis and shrinkage of the submucosal myoma after
      microwave endometrial ablation. Prediction of the shrinkage rate of submucous
      myomas appears to be possible by calculating the RODNeV preoperatively.

PMID- 19751334
TI  - Port wound closure assisted by Foley catheter: an easier way to provide fascia
      security.
AB  - AIM: Specific laparoscopy-related complications, such as incisional hernia
      (trocar hernia) or hemorrhage, are worthy of our special attention. Preventing
      and managing these complications safely and efficiently are important, suggesting
      that a definite closure of the 10-12 mm port wound after laparoscopy is needed;
      for this, a newer, simpler method was used. METHODS: Ninety-six patients with
      benign ovarian tumor warranting laparoscopic surgery were enrolled into the
      study. Forty-eight patients (50%) underwent a Foley catheter-assisted port wound
      closure (Foley group) and the remaining patients (50%) underwent a conventional
      port would closure (control group). The outcome was measured by comparing
      operative time, the amount of suture material used (difficulty of wound closure),
      therapeutic efficacy (hernia), postoperative complications (bleeding, hematoma,
      and wound pain by a self-reported six-point verbal numeric rating scale (VNRS-6))
      and anesthesia use as measured by an analgesic usage score (AUS), and
      dissatisfaction with the cosmetic results, in both groups. RESULTS: The general
      characteristics of the patients were similar in both groups. There were no
      statistical differences in mean operative time, therapeutic efficacy, and
      postoperative complications between the two groups. However, the amount of extra
      suture material needed was significantly less in the Foley group compared to the
      control group (1.04 +/- 0.08 vs 1.29 +/- 0.44, P = 0.015, and 4.2 vs 25%, P =
      0.02, respectively). CONCLUSION: Wound closure with the assistance of a Foley
      catheter offers an easy and secure way to close a 10-12 mm port wound.

PMID- 19751335
TI  - Prospective assessment of overactive bladder symptoms in women who have undergone
      transvaginal surgery for advanced vaginal wall prolapse: a preliminary report.
AB  - AIM: To evaluate the changes in symptoms of overactive bladder (OAB) on the
      advanced cystocele after restoration of prolapse using the Perigee system.
      METHODS: This prospective clinical study recorded 16 women for the Perigee
      procedure due to advanced cystocele with OAB symptoms. Prolapse assessment was
      measured according to the pelvic organ prolapse quantization system. Complete
      urodynamic examination was performed before and six months after the operation.
      Subjects were also asked to fill in a questionnaire before and after the
      operation for a quantitative assay of OAB symptoms. Additional pelvic
      reconstructive surgeries including the Apogee procedure, retropubic tension-free
      vaginal tape and posterior colporrhaphy with tension-free vaginal tape were
      performed concurrently on 10 patients. RESULTS: Eleven cases were available for
      data analysis. Results showed significant improvement at points Aa and Ba after
      the operation. The Perigee procedure could restore the advanced cystocele
      adequately, with points Aa and Ba almost back to their normal physiological and
      anatomical positions. However, urodynamics showed two subjects with motor urgency
      and one with sensory urgency having objective improvement in urge sensation.
      Questionnaire results of postoperative subjective symptoms revealed a significant
      improvement with respect to coping, concern and sleep as compared to preoperative
      symptoms. CONCLUSION: This preliminary report reveals that the Perigee procedure
      is an efficient and effective surgical approach for the treatment of anterior
      vaginal wall prolapse. It can also improve the subjective symptoms of OAB.

PMID- 19751336
TI  - Urine leakage related to physical fatigue in women with urinary stress
      incontinence.
AB  - OBJECTIVE: To evaluate the frequency of urine leakage related to physical fatigue
      in women presenting with urinary stress incontinence using a specific
      questionnaire, and to assess its association with the Bristol Female Lower
      Urinary Tract Symptoms questionnaire and urodynamic findings. DESIGN: Prospective
      observational descriptive study. SETTING: University hospital (urodynamics
      laboratory). PARTICIPANTS: Sixty-one women presenting with urinary stress
      incontinence and 10 continent women. INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURES: The participants underwent urethral pressure profile measurement and
      completed a Bristol Female Lower Urinary Tract Symptoms questionnaire and a
      specific questionnaire focused on urine leakage related to physical fatigue.
      RESULTS: Twenty-three (37%) women with urinary stress incontinence claimed to
      exhibit urine leakage related to physical fatigue more often than one third of
      the time and 47% claimed to exhibit urinary leakage only after more than one
      cough. There was a positive correlation between the findings of the specific
      questionnaire and the presence of a sharp decrease in urethral pressure following
      repeated cough efforts: question #1 (P = 0.02); question #2 (P = 0.00002);
      question #3 (P = 0.04). CONCLUSION: There is a strong association between this
      questionnaire focused on urine leakage related to fatigue and the presence of a
      decrease in urethral pressure following repeated coughs.

PMID- 19751337
TI  - Efficacy and safety of ormeloxifene in management of menorrhagia: a pilot study.
AB  - OBJECTIVE: To assess the efficacy and safety of ormeloxifene (centchroman) in the
      medical management of menorrhagia. METHODS: Forty-two women with menorrhagia were
      recruited for the study. Ormeloxifene was given to each patient 60 mg twice a
      week for 3 months and then once a week for 1 month. Patients were followed up at
      2 and 4 months of therapy, then at 3 and 6 months after treatment was stopped.
      Menstrual blood loss (MBL) was measured objectively by a pictorial blood loss
      assessment chart (PBAC) score and subjectively by a visual analog scale (VAS).
      RESULTS: The pretreatment median PBAC score was 388 (range 169-835). Eighteen
      patients (42.9%) had amenorrhea with the therapy. Median PBAC reduced to 80
      (range 0-730) and 5 (range 0-310) at 2 and 4 months, respectively (P-value
      <0.001); thus, the percentage reduction was 97.7% at 4 months. Seven patients
      (16.7%) had no response and three (7.1%) discontinued treatment before 4 months.
      During the 10-month study period, 21% of the patients underwent hysterectomy.
      Adverse effects included ovarian cyst (7.1%), cervical erosion and discharge
      (7.1%), gastric dyspepsia (4.8%), vague abdominal pain (4.8%) and headache
      (4.8%). CONCLUSION: Ormeloxifene is an effective and safe therapeutic option for
      the medical management of menorrhagia.

PMID- 19751338
TI  - McGill Pain Questionnaire: a multi-dimensional verbal scale assessing
      postoperative changes in pain symptoms associated with severe endometriosis.
AB  - BACKGROUND: Objective evaluation of pelvic pain symptoms using a standard pain
      questionnaire is essential to assessing the treatment of endometriosis and
      related pain. AIM: To evaluate the McGill Pain Questionnaire (MPQ) as a multi
      dimensional verbal scale in providing information about chronic pelvic pain
      associated with endometriosis, before and after laparoscopic surgery. METHODS:
      Fifty-five women undergoing laparoscopy for severe endometriosis were asked to
      complete the MPQ before surgery and at the 6-month follow up. All patients
      presented with preoperative pain symptoms of variable severity. We obtained the
      pain indexes and studied their relation with: patients' characteristics (age,
      body mass index, parity, qualification, occupation); operative findings (number,
      site and size of endometriotic lesions and presence of pelvic adhesions); and
      postoperative evolution of variable MPQ pain indexes at the 6-month follow up.
      RESULTS: Median present pain index (PPI) (index of pain intensity), before
      surgical treatment was 3 (2-4): preoperative PPI was <2 in 25% of patients while
      25% of patients had PPI > 4. Overall median PPI after surgical treatment was 1 (0
      2): postoperative index of pain intensity was <1 in 50% of patients, >2 in 25% of
      patients while 25% of patients did not experience postoperative pain. Overall
      pain intensity significantly decreased after laparoscopic treatment of
      endometriosis (Wilcoxon test P < 0.0005). None of the patients' characteristics
      were found to be significantly correlated with the severity or improvement of
      preoperative pain at postoperative follow up (P > 0.05), and the intensity of
      preoperative pain was not correlated to any of the operative variables. There was
      a significant reduction in all individual MPQ pain indexes; however 18.2% of
      women did not show improvement of pain symptoms after laparoscopic surgery. An
      increasing endometrioma diameter was associated with a significant decrease in
      the difference in evaluative rank score of pain rating index between pain indexes
      at the 6-month follow up and preoperatively (P = 0.04, Spearman's rank
      correlation Rho = -0.277). CONCLUSIONS: MPQ appears to be useful as a multi
      dimensional scale in describing patients' pain semiology and evaluating pain
      evolution after surgical treatment. However, due to the extreme variability of
      pain experience, MPQ results don't clarify the relationship between pain
      intensity and the severity of endometriosis.

PMID- 19751339
TI  - The dynamics of obstetricians and gynecologists in Japan: a retrospective cohort
      model using the nationwide survey of physicians data.
AB  - AIM: A shortage of obstetricians and gynecologists (OB/GYNs) in Japan has been
      highlighted. We conducted a descriptive and retrospective cohort study using data
      from the Survey of Physicians in Japan, and analyzed the dynamics of OB/GYNs.
      METHODS: We calculated the total numbers of OB/GYNs, their average age, the
      percentage of female OB/GYNs, hospital OB/GYNs, and the number of OB/GYNs in
      rural areas in 1974, 1984, 1994 and 2004. We determined the number of physicians
      who participated in and left the specialty of obstetrics and gynecology. The
      withdrawal rates of OB/GYNs who graduated in 1972, 1982 and 1992 were
      retrospectively followed using survival analysis. RESULTS: The overall number of
      physicians has increased, while the number of OB/GYNs has remained almost
      unchanged over the past 30 years. The percentage of female OB/GYNs has increased.
      Fewer new graduates chose obstetrics and gynecology, the withdrawal rate of
      current OB/GYNs decreased, and their average age (50.8 years) increased. The
      trend in withdrawal rates did not differ significantly among the generations.
      CONCLUSIONS: The gravest problem in the OB/GYNs workforce is the continued
      decline in newly graduated OB/GYNs. Improvements in working conditions and job
      satisfaction are considered vital.

PMID- 19751340
TI  - Emergency contraception: knowledge, attitude and prescription practice among
      doctors in different specialties in Hong Kong.
AB  - AIM: Few studies have evaluated doctors' knowledge, attitudes and practices as
      regards emergency contraception (EC). Some studies have reported inadequate
      knowledge, bias and wrong prescriptions by doctors. This article compares the
      prescription pattern, attitude and knowledge of EC in Hong Kong doctors in
      different specialties. METHODS: Questionnaires were mailed to family physicians,
      obstetrician-gynecologists and doctors working in family planning clinics to
      ascertain their attitudes to EC. Those who provided EC described the types of EC
      used, whether drugs were given in advance and answered a 12-question knowledge
      test. Those who did not provide EC stated why. RESULTS: A total of 443 completed
      questionnaires were analyzed: 70.9% of doctors agreed that the benefits of EC
      outweigh its risks and 61.2% agreed that doctors should discuss it with clients.
      Advanced provision was supported by 54.2% of doctors but reduced to 32.5% if the
      target client was a girl aged 16 or below. Even fewer doctors (40.2%) supported
      the over-the-counter sales of EC pills. In the knowledge test, family planning
      doctors scored 10.45 out of 12 and obstetrician-gynecologists in private practice
      had the lowest score of 6.08. Family planning doctors used levonorgestrel pills
      while private family physicians and obstetrician-gynecologists used Yuzpe. Among
      352 doctors who provided EC, only 21.7% of private family physicians and 15.9% of
      private obstetrician-gynecologists prescribed it in advance. CONCLUSIONS: Only
      doctors working in family planning clinics were competent in their knowledge of
      emergency contraception and up to date with current practice. Although half of
      the doctors supported advanced provision, few implemented it. Most doctors did
      not support advanced provision to young girls nor the over-the-counter sales of
      EC pills.

PMID- 19751341
TI  - Chlamydia trachomatis infections and the risk of ectopic pregnancy in Khon Kaen
      women.
AB  - AIM: To determine the prevalence of Chlamydia trachomatis infection and to
      evaluate the relation of previous and persistent chlamydial infection to ectopic
      pregnancy (EP) among women in Khon Kaen, Thailand. METHODS: We enrolled 32 EP
      patients in the case group. Control subjects were 57 women undergoing tubal
      ligation after normal labor. Serum immunoglobulin (Ig)G and IgA antibodies to C.
      trachomatis were determined using ELISA. Chlamydial DNA was investigated using
      polymerase chain reaction. RESULTS: The prevalence of chlamydial DNA in fallopian
      tube tissue was 34.38% of EP patients whereas none was detected in controls. In
      cervical cells, however, no significant difference in chlamydial DNA between
      cases (3.13%) and controls (3.51%) was detected. Serum-specific IgG was found
      more in the EP group than in the control group (21.88% and 5.26%, respectively; P
      < 0.05). Serum-specific IgA was detected in 5.26% of the control women but not in
      the EP group. Analysis by multivariate conditional logistic regression revealed a
      significant association between EP and the various risk factors. Among these,
      abortion, previous EP and age at first intercourse <15 years were strong
      predictors of EP. However, the association between specific IgG and EP became non
      significant in this analysis. CONCLUSIONS: No strong independent association was
      shown between chlamydial antibodies and the EP risk in Thai women despite DNA
      detection in fallopian tube tissue. In contrast, factors including abortion,
      previous EP, and age at first intercourse <15 years were the significant
      predictors of EP. Efforts to address these other variables will help more in
      reducing the EP burden in Thai women compared to eliminating C. trachomatis.

PMID- 19751342
TI  - The efficacy of preoperative hormonal therapy before laparoscopic cystectomy of
      ovarian endometriomas.
AB  - AIM: The aim of this study was to investigate the influence of preoperative
      hormonal therapy before laparoscopic cystectomy of ovarian endometriomas. We
      identified differences in follicle loss and surgical difficulties with or without
      preoperative hormonal therapy. METHODS: Ninety-six patients with ovarian
      endometrioma underwent a laparoscopic cystectomy. Patients were divided into
      three groups: control group A (53 patients, 57 cysts) with no preoperative
      hormonal therapy; group B (34 patients, 40 cysts) who received gonadotropin
      releasing hormone agonist therapy; and group C (9 patients, 11 cysts) who
      received danazol therapy before surgery. The medical and videotape records of all
      patients were retrospectively reviewed. The specimens of endometriomas were
      histologically evaluated. RESULTS: Mean diameters of endometriomas before
      hormonal therapy in groups B and C were significantly greater than those in the
      control group. There were no significant differences in the following: the mean
      diameter of removed cysts, the revised-American Society of Reproductive Medicine
      scores, the number of capsules containing follicle(s), and the mean number of
      follicles attached to a cyst. However, the number of capsules showing fibrosis
      significantly increased in the preoperative hormonal therapy groups (P < 0.001).
      Furthermore, the mean operation time of the preoperative hormonal groups was
      significantly longer than that of the control group (P < 0.01, P < 0.001).
      CONCLUSION: Our data suggested that preoperative hormonal therapy reduced the
      size of endometriomas. However, with similar revised-American Society of
      Reproductive Medicine scores, preoperative hormonal therapy did not contribute to
      the reduction of the loss of ovarian follicles. Fibrosis resulting from hormonal
      therapy appears to be responsible for these observations.

PMID- 19751343
TI  - Postpartum subarachnoid hemorrhage due to Moyamoya disease associated with renal
      artery stenosis.
AB  - Moyamoya disease is a cerebrovascular stenotic or occlusive disease predominantly
      seen in Asian countries. Sometimes there are coexisting renal artery lesions in
      Moyamoya disease patients. A 32-year-old multipara had a cesarean section at 33
      gestational weeks due to preeclampsia. One month later, she developed
      subarachnoid hemorrhage and angiography demonstrated Moyamoya vessels with renal
      artery stenosis. After conservative therapy, the patient was discharged without
      any deficits. Our conclusion is that patients with Moyamoya disease carry a risk
      of cerebrovascular accident during pregnancy and postpartum. In this case, we did
      not diagnose Moyamoya disease with renal artery stenosis until the patient
      developed subarachnoid hemorrhage. It is very important to make a careful
      differential diagnosis of hypertension during pregnancy and the postpartum
      period.

PMID- 19751344
TI  - Serious adverse drug reaction in a woman with hyperemesis gravidarum after first
      exposure to vitamin B complex containing vitamins B1, B6 and B12.
AB  - We report the case of a pregnant woman who suffered from hypotension after first
      exposure to intravenous administration of a combination drug containing vitamins
      B1, B6 and B12 (Vitamedin; Daiichi-Sankyo, Tokyo, Japan). A 27-year-old Japanese
      woman received an intravenous infusion of fluid containing a vitamin B complex
      due to hyperemesis gravidarum. Thirty minutes after the start of infusion she was
      found to be in hypotension. The patient had stupor, general sweating, blood
      pressure of 82/50 mmHg, and low percutaneous oxygen saturation (SpO(2)) of 88%.
      We immediately stopped the infusion, lifted her legs and administered oxygen.
      Three minutes after these treatments, she quickly recovered to a good general
      condition. A skin prick test for vitamin B12 was positive, but tests for B1, B6,
      mannitol and saline were negative, indicating this adverse reaction was one of
      drug hypersensitivity due to the vitamin B12 in Vitamedin. Patients should be
      observed carefully immediately after the administration of Vitamedin.

PMID- 19751345
TI  - Hypovolemic shock due to massive edema of a pedunculated uterine myoma after
      delivery.
AB  - Although most patients with uterine myomas are asymptomatic during pregnancy,
      profound enlargement of a pedunculated myoma has serious consequences. In the
      present case, gradual enlargement of a pedunculated myoma was observed throughout
      a woman's pregnancy, worsening after delivery and causing hypovolemic shock,
      without evidence of external or intra-abdominal hemorrhage. Laparotomy revealed a
      severely edematous myoma containing a large amount of blood. It is speculated
      that partial occlusion had obstructed venous return, but not arterial blood flow,
      which caused rapid enlargement of the myoma.

PMID- 19751346
TI  - Ehlers-Danlos type IV in pregnancy with a history of myocardial infarction.
AB  - Ehlers-Danlos syndrome (EDS) type IV is an autosomal dominantly inherited
      connective tissue disorder caused by abnormal type III collagen resulting from
      heterogenous mutations of the type III procollagen gene (COL3A1). The maternal
      mortality rate per pregnancy in EDS type IV has been reported as 11.5% to 25%. A
      30-year-old Japanese primiparous woman, with a brother who had suffered a bowel
      rupture due to EDS type IV, became pregnant. She also suffered from myocardial
      infarction due to coronary artery dissections at 24 years old, and underwent
      coronary artery bypass grafting. Due to uncontrollable uterine contractions, beta
      2-stimulants were administered during 18 to 29 weeks of gestation. Therefore, we
      performed a cesarean section at 29 weeks of gestation to prevent uterine rupture.
      She and her baby were discharged without any complications. It was revealed that
      she had the same mutation as her brother, Gly220Trp, in the (Gly-X-Y)n repeat of
      the triple-helical domain of COL3A1.

PMID- 19751347
TI  - Use of Chinese herbal medicine 'meizitanc' in pregnancy: report of three cases.
AB  - The Chinese herbal medicine 'meizitanc', known as 'LiDa Dai Dai Hua Jiao Nang'
      (Kunming Dali Industry and Trade, Kunming, Yunnan, China) has been used by many
      women to support weight loss, even though life-threatening side-effects and
      deaths have been reported. We report the outcomes of three cases of exposure to
      'meizitanc' during early pregnancy. In the first case, the pregnancy continued
      after the patient stopped taking the drug and at 38 weeks of gestation, the
      patient delivered a healthy infant. However, in the second and third cases fetal
      cardiac activities were not detected on obstetric follow-up and both pregnancies
      were terminated due to missed abortion. To our knowledge, this is the first
      report of exposure to meizitanc during pregnancy. Although herbal medicines are
      presumed to be safe because of their natural origin, consumption of such products
      may be dangerous due to the content of undeclared drugs, adulteration with
      multiple substances and contamination with toxic metals.

PMID- 19751348
TI  - Acute mesenteric venous thrombosis due to protein S deficiency in a pregnant
      woman.
AB  - Acute mesenteric venous thrombosis is a rare and potentially fatal disease, which
      often occurs in medically compromised elderly patients. Isolated mesenteric
      venous thrombosis may be encountered in young women who have underlying
      hypercoagulable disease. We report a case of mesenteric venous thrombosis in a
      young pregnant woman in whom protein S deficiency was diagnosed at a later stage.
      The patient underwent extensive bowel resection. On follow-up she had developed
      an obstruction on the intestinal anastomosis. The anastomosis was revised, but
      the patient died of intervening complications 3 months after the operation. Early
      management of acute mesenteric venous thrombosis relies on early diagnosis, which
      requires a high index of suspicion. The condition must be considered during
      evaluation of persistent abdominal pain in pregnant women with hypercoagulable
      disorder.

PMID- 19751349
TI  - Postoperative abdominal aspergilloma mimicking cervical cancer recurrence and
      diagnostic imaging, including F-fluorodeoxyglucose positron emission tomography,
      with false-positive findings.
AB  - We present the case of a 39-year-old woman with a subfascial abscess. The patient
      had undergone radical hysterectomy for stage Ib1 cervical cancer. Six months
      after the surgery, she was found to have an elevated concentration of the serum
      squamous cell carcinoma antigen. Thereafter, she underwent magnetic resonance
      imaging and positron emission tomography-computed tomography. Magnetic resonance
      imaging revealed an irregular mass (diameter: 2 cm) in the abdominal wall.
      Increased (18)F-fluorodeoxyglucose uptake into the mass was observed on positron
      emission tomography. Therefore, we could not rule out the possibility of the
      peritoneal dissemination of cervical cancer, and we resected the mass. The mass
      was pathologically and microbiologically diagnosed as a subfascial aspergilloma.
      The lesion was located in the subfascial area where a drain was inserted at the
      time of the primary laparotomy.

PMID- 19751350
TI  - Lymphangioma of the ovary accompanied by chylous ascites.
AB  - Lymphangioma of the ovary is very rare, with only 17 cases reported to date. In
      this report, a 43-year-old woman with lymphangioma of the ovary accompanied by
      chylous ascites is described. Vaginal ultrasound showed a solid cystic tumor at
      the right ovary accompanied by ascites. The volume of ascites was changeable.
      Milky fluid obtained by Douglas pouch aspiration contained numerous mature
      lymphocytes. She underwent right salpingo-oophorectomy. Histological examination
      revealed that the excised tumor from the right ovary was consistent with benign
      lymphangioma. This is the first case report of lymphangioma of the ovary
      accompanied by chylous ascites. We should discriminate such cases from other
      malignant tumors in order to avoid overtreatment.

PMID- 19751351
TI  - Pseudoangiomatous stromal hyperplasia (PASH) of the breast: intraductal
      appearance.
AB  - Pseudoangiomatous stromal hyperplasia (PASH) is a benign proliferative lesion of
      breast stroma. The diagnosis of PASH can be made using imaging techniques such as
      ultrasound, magnetic resonance or mammography. Ductoscopy is a relatively new
      technique which is used for imaging the intraductal surface. We report a patient
      with PASH in whom ductoscopy was performed successfully.

PMID- 19751352
TI  - Uterine compression suture against impending recurrence of uterine inversion
      immediately after laparotomy repositioning.
AB  - Uterine compression suture to prevent impending recurrence of uterine inversion
      after laparotomy repositioning has not been reported previously. A 28-year-old
      primigravid woman demonstrated uterine inversion. Although Huntington's procedure
      had successfully repositioned the uterus, acute recurrence of inversion with
      uterine atony appeared to be impending during the surgery. We applied modified
      uterine compression sutures, which prevented the recurrence of inversion and
      achieved complete hemostasis. Three years later, the patient became pregnant and
      vaginally delivered a term infant. Thereafter, uterine inversion recurred, and
      was repositioned manually. Uterine compression suture may be of use not only for
      hemostasis for postpartum hemorrhage, but also for prophylaxis against acute
      recurrence of uterine inversion.

PMID- 19751353
TI  - Unilateral ovarian metastasis in a case of squamous cervical carcinoma IA1.
AB  - Ovarian metastasis from early-stage squamous cervical cancer is rare. We report a
      case of unilateral ovarian metastasis from squamous cervical cancer IA1. Although
      ovarian metastasis from early-stage squamous cervical cancer is rare,
      gynecological oncologists should not overlook its possibility.

PMID- 19751354
TI  - Surgery-assisted reproductive technology hybrid therapy: a reproductive procedure
      for an infertile woman of late reproductive age with multiple myomas.
AB  - AIM: To produce a successful pregnancy in a 38-year-old infertile patient with
      relapsed myoma using a technique we refer to as 'surgery-assisted reproductive
      technology (ART) hybrid therapy' because it combines ART for cryopreservation of
      in vitro fertilized eggs with reproductive surgery. METHODS: A 38-year-old
      nulliparous woman who had undergone abdominal myomectomy and in whom magnetic
      resonance imaging showed multiple myomas was treated at our University-affiliated
      hospital and outpatient clinic. Blastocysts were cryopreserved during the
      preoperative period. Laparoscopic myomectomy was performed after preoperative
      treatment with a GnRH agonist. Ten months after the operation, the youngest
      cryopreserved blastocyst was transferred into the uterus and implanted
      successfully. RESULTS: Treatment resulted in successful implantation and
      pregnancy. In January 2008, the course of pregnancy had been uneventful and the
      patient gave birth to a male infant weighing 2998 grams by cesarean section at 37
      weeks of gestation. CONCLUSION: We have treated eight patients using hybrid
      therapy with encouraging results, and we describe these cases herein briefly.

PMID- 19751355
TI  - Laparoscopy-aided medical or surgical treatment for tubal pregnancy.

PMID- 19751357
TI  - Comparison of two resorbable membrane systems in bone regeneration after removal
      of wisdom teeth: a randomized-controlled clinical pilot study.
AB  - OBJECTIVES: To compare the performance and safety of Inion GTR(TM) Biodegradable
      Membrane System and Geistlich resorbable bilayer Bio-Gide((R)) membrane in human
      bone regeneration. MATERIAL AND METHODS: In a multicenter, split blind,
      comparative, randomized, prospective, pilot study 15 patients have been
      randomized at surgery whether to be treated either with Inion GTR(TM)
      Biodegradable Membrane System on one and Geistlich resorbable bilayer Bio
      Gide((R)) membrane on the other side or vice versa after surgical removal of both
      fully impacted wisdom teeth. During the follow-up visits at week 1, 2 and 6 and
      at months 3 and 6 the general state, the wound, eventual adverse events and the
      medication of the patients were assessed. Computed Tomography (CT) scans were
      performed immediately and 3 months after the surgery, before biopsy collection.
      Semi-quantitative histological evaluation and histomorphometric analyses were
      performed according to the ISO 10993-6 standard. New bone formation and membrane
      integration were evaluated by CT scan measurements. Tissue healing was evaluated
      clinically and by photographs between the time on teeth extraction and during
      follow ups. RESULTS: Five patients were smokers, none drank alcohol. Mild adverse
      events like wound infection, haematoma or late swelling of the gums occurred in
      three patients. The trephine bur harvest of bone biopsies under local anaesthesia
      was uneventful. Whereas specimens from the sites treated with the Inion membrane
      yielded 17.0% (SD 24%), the Bio-Gide membrane sites yielded 13.5% (SD 15%) of
      bone tissue density. In sites treated with the Inion membrane, 9.5% of old bone
      density and 7.5% of newly formed bone could be found, whereas the Bio-Gide((R))
      membrane sites showed 3.8% of old bone density and 9.8% of newly formed bone.
      There were no statistically significant differences between the two groups with
      respect to the two variables. The osteoid rim was more extended with the Bio
      Gide((R)) (6.6 mm) than with the Inion membrane (5.1 mm) but the difference
      between the two treatments did not reach statistical significance. Highly
      significant reductions in the area of the defect with both membranes were
      detected with significant increases in CT density at the immediate inferio-buccal
      adjacent bone and in the surgical defect area with both membranes. However, there
      was neither significant change in CT density in the immediate inferior-lingual
      adjacent bone of the two membranes, nor significant difference between the
      membranes on any of the four measurements (area of defect: P=0.1354; CT density
      immediate inferio-buccal adjacent bone: P=0.7615; CT density surgical defect
      area: P=0.1876; CT density immediate inferio-lingual adjacent bone: P=0.4212).
      CONCLUSION: The overall clinical outcome was satisfying and the majority of the
      patients showed an uneventful healing phase. Both membranes presented similar
      capacities regarding their barrier function and were associated with analogous
      bone regeneration. No statistically valid evidence about the superiority of one
      particular membrane was obtained. For the patient the only difference is that one
      product is animal derived and the other synthetic.

PMID- 19751359
TI  - Antigenic variation in the African trypanosome: molecular mechanisms and
      phenotypic complexity.
AB  - Antigenic variation is an immune evasion strategy that has evolved in viral,
      bacterial and protistan pathogens. In the African trypanosome this involves
      stochastic switches in the composition of a variant surface glycoprotein (VSG)
      coat, using a massive archive of silent VSG genes to change the identity of the
      single VSG expressed at a time. VSG switching is driven primarily by
      recombination reactions that move silent VSGs into specialized expression sites,
      though transcription-based switching can also occur. Here we discuss what is
      being revealed about the machinery that underlies these switching mechanisms,
      including what parallels can be drawn with other pathogens. In addition, we
      discuss how such switching reactions act in a hierarchy and contribute to
      pathogen survival in the face of immune attack, including the establishment and
      maintenance of chronic infections, leading to host-host transmission.

PMID- 19751360
TI  - Measuring irritable bowel syndrome patient-reported outcomes with an abdominal
      pain numeric rating scale.
AB  - BACKGROUND: Controversy exists on how to measure patient-reported outcomes in
      irritable bowel syndrome (IBS) clinical trials effectively. Pain numeric rating
      scales (NRS) are widely used in the non-IBS pain literature. The Food and Drug
      Administration has proposed using the NRS in IBS. AIM: To test the psychometrics
      of an abdominal pain NRS in IBS. Methods We analysed data from a longitudinal
      cohort of Rome III IBS subjects. At entry, subjects completed a 10-point NRS,
      bowel symptoms, IBS severity measurements (IBS-SSS, FBDSI), health-related
      quality of life indices (IBS-QOL, EQ5D), and the Worker Productivity Activity
      Index (WPAI). We repeated assessments at 3 months along with a response scale to
      calculate the minimal clinically important difference. RESULTS: There were 277
      subjects (82% women; age = 42 +/- 15) at baseline and 90 at 3 months. The NRS
      correlated cross-sectionally with IBS-SSS (r = 0.60; P < 0.0011), FBDSI (r =
      0.49; P < 0.0001), IBS-QOL (r = 0.43; P < 0.0001), EQ5D (r = 0.48; P < 0.0001),
      presenteeism (r = 0.39; P < 0.0001), absenteeism (r = 0.17; P = 0.04) and
      distension (r = 0.46; P < 0.0001), but not stool frequency or form. The minimal
      clinically important difference was 2.2 points, correlating with a 29.5%
      reduction over time. CONCLUSIONS: An abdominal pain NRS exhibits excellent
      validity and can be readily interpreted with a minimal clinically important
      difference in patients with IBS. These data support the use of the NRS in IBS
      clinical trials.

PMID- 19751361
TI  - Different neural circuits underlie different cross-modal spatial judgments
      (commentary on Passamonti et al.).

PMID- 19751362
TI  - Fertile bull sperm aneuploidy and chromatin integrity in relationship to
      fertility.
AB  - Aneuploidy is associated with spontaneous abortions, perinatal mortality, mental
      retardation and with embryonic and foetal mortality. Most of these abnormalities
      originate as a result of meiosis errors during gametogenesis. The main purpose of
      the study was to analyse frequency of aneuploidies of sex chromosomes and
      chromosome 6 by three-colour fluorescence in situ hybridization (FISH) in 47
      young bulls, candidates for artificial insemination programme with cryopreserved
      semen and to investigate the influence of aneuploidies and disturbed sperm
      chromatin integrity on non-return rates, the frequencies of abortions, perinatal
      mortality and stillbirths. The average frequencies of spermatozoa with disomy for
      chromosomes X, Y, XY and 6 were 0.032, 0.005, 0.003 and 0.039% respectively. The
      incidence of XX66, YY66 and XY66 diploidy was 0.017, 0.006 and 0.015%
      respectively. Frequencies of meiotic II errors were significantly higher than
      meiotic I errors (p < 0.01). More X bearing spermatozoa than Y bearing
      spermatozoa were detected (5151 vs. 5022; p < 0.01). Sperm chromatin damage
      expressed by DNA fragmentation index (DFI) was 5.3 +/- 3.7 and percentage of
      cells with defective chromatin condensation (HDS) was 1.4 +/- 0.8. No correlation
      was found between sperm aneuploidy and basic sperm analysis. The relationship was
      found between non-return rate and total aneuploidy (r = -0.310; p = 0.036).
      Significant correlation was found between sex disomy, total aneuploidy (disomy of
      chromosomes 6, X, Y and XY spermatozoa and diploidy) and stillbirths (r = 0.390;
      p = 0.013; and r = 0.331; p = 0.037). Chromosome 6 disomy correlated with
      perinatal mortality (r = 0.317; p = 0.047). HDS correlated significantly with
      total aneuploidy (r = 0.449; p = 0.002). Our study indicated that aneuploidy
      frequencies in young fertile bull spermatozoa are relatively low. Nevertheless,
      there exists a variability in aneuploidy frequencies amongst bulls, which appears
      to be able to have an influence on the fertility of these animals.

PMID- 19751363
TI  - Assessment of mitochondrial potential: implications for the correct monitoring of
      human sperm function.
AB  - Mitochondrial membrane potential (MMP) is an indicator of sperm functionality
      that can be assessed using specific fluorescent markers. However, the ability of
      distinct probes to dynamically evaluate sperm MMP has not been determined. In the
      present study, human sperm samples were independently labelled with MitoTracker
      Green, MitoTracker Red and JC-1. The ability of each probe to correctly monitor
      MMP was determined by incubating sperm with MMP disruptors (KCN, FCCP and
      valinomycin). Similarly, the effect of distinct fixatives (formaldehyde and
      methanol) was also tested. The three mitochondrial probes provided similar
      results, and were able to monitor changes in MMP when sperm had been previously
      incubated with MMP-disrupting agents. However, only JC-1 could, to a small
      extent, mirror MMP alterations after sperm labelling. Unexpectedly, the three
      probes were able to stain some pre-fixed sperm, even though this behaviour was
      very variable, especially for MitoTrackers. On the other hand, none of the probes
      was shown to be reliably fixable. Of the three probes tested JC-1 seems to be the
      most adequate, nevertheless, the choice of an MMP-specific probe may depend on
      the aim of each experimental setting and appropriate controls must always be
      performed.

PMID- 19751364
TI  - Towards a combined prognostic index for survival in HIV infection: the role of
      'non-HIV' biomarkers.
AB  - BACKGROUND: As those with HIV infection live longer, 'non-AIDS' condition
      associated with immunodeficiency and chronic inflammation are more common. We ask
      whether 'non-HIV' biomarkers improve differentiation of mortality risk among
      individuals initiating combination antiretroviral therapy (cART). METHODS: Using
      Poisson models, we analysed data from the Veterans Aging Cohort Study (VACS) on
      HIV-infected veterans initiating cART between 1 January 1997 and 1 August 2002.
      Measurements included: HIV biomarkers (CD4 cell count, HIV RNA and AIDS-defining
      conditions); 'non-HIV' biomarkers (haemoglobin, transaminases, platelets,
      creatinine, and hepatitis B and C serology); substance abuse or dependence
      (alcohol or drug); and age. Outcome was all cause mortality. We tested the
      discrimination (C statistics) of each biomarker group alone and in combination in
      development and validation data sets, over a range of survival intervals, and
      adjusting for missing data. RESULTS: Of veterans initiating cART, 9784 (72%) had
      complete data. Of these, 2566 died. Subjects were middle-aged (median age 45
      years), mainly male (98%) and predominantly black (51%). HIV and 'non-HIV'
      markers were associated with each other (P < 0.0001) and discriminated mortality
      (C statistics 0.68-0.73); when combined, discrimination improved (P < 0.0001).
      Discrimination for the VACS Index was greater for shorter survival intervals [30
      day C statistic 0.86, 95% confidence interval (CI) 0.80-0.91], but good for
      intervals of up to 8 years (C statistic 0.73, 95% CI 0.72-0.74). Results were
      robust to adjustment for missing data. CONCLUSIONS: When added to HIV biomarkers,
      'non-HIV' biomarkers improve differentiation of mortality. When evaluated over
      similar intervals, the VACS Index discriminates as well as other established
      indices. After further validation, the VACS Index may provide a useful,
      integrated risk assessment for management and research.

PMID- 19751365
TI  - Generic topiramate for migraine prevention: is bioequivalence the same as
      therapeutic equivalence?

PMID- 19751366
TI  - Topiramate-induced intractable cough during migraine prophylaxis.
AB  - Topiramate is a highly effective drug in migraine prophylaxis and is considered a
      first-line treatment. The evidence for the efficacy of topiramate is based upon
      the results of several large, randomized, double-blind, placebo-controlled
      trials. Adverse events (AEs) are common and require discontinuation of the
      treatment in about 20-25% of patients, but they are rarely severe. There are
      reviews regarding topiramate-related AEs representing a large number of patients
      treated in controlled trials. The most common AEs are weight loss, dizziness,
      somnolence, abnormal thinking, fatigue, ataxia, confusion, paresthesias, impaired
      concentration, nervousness, amnesia, and language difficulties. The development
      of cough has never been reported as an AE during topiramate prophylaxis for
      migraine. We present 3 cases in which the prophylactic treatment for migraine
      with topiramate was discontinued due to the onset of primary intractable
      coughing.

PMID- 19751367
TI  - A case of MS presenting with SUNCT status.

PMID- 19751368
TI  - Nitric oxide-induced changes in endothelial expression of phosphodiesterases 2,
      3, and 5.
AB  - OBJECTIVE: To investigate nitric oxide (NO)-mediated changes in expression of
      cyclic nucleotide degrading phosphodiesterases 2A (PDE2A), PDE3B, and PDE5A in
      human endothelial cells. BACKGROUND: Nitric oxide induces production of cyclic
      guanosine monophosphate (cGMP), which along with cyclic adenosine monophosphate
      (cAMP) is degraded by PDEs. NO donors and selective inhibitors of PDE3 and PDE5
      induce migraine-like headache and play a role in endothelial dysfunction during
      stroke. The current study investigates possible NO modulation of cGMP-related
      PDEs relevant to headache induction in a cell line containing such PDEs. METHODS:
      Real time polymerase chain reaction and Western blots were used to show
      expression of PDE2A, PDE3B, and PDE5A in a stable cell line of human brain
      microvascular endothelial cells. Effects of NO on PDE expression were analyzed at
      specific time intervals after continued DETA NONOate administration. RESULTS:
      This study shows the expression of PDE2A, PDE3B, and PDE5A mRNA and PDE3B and
      PDE5A protein in human cerebral endothelial cells. Long-term DETA NONOate
      administration induced an immediate mRNA up-regulation of PDE5A (1.9-fold, 0.5
      hour), an early peak of PDE2A (1.4-fold, 1 and 2 hours) and later up-regulation
      of both PDE3B (1.6-fold, 4 hours) and PDE2A (1.7-fold, 8 hours and 1.2-fold after
      24 hours). Such changes were, however, not translated into significant changes in
      protein expression indicating few, if any, functional effects. CONCLUSIONS: Long
      term NO stimulation modulated PDE3 and PDE5 mRNA expression in endothelial cells.
      However, PDE3 and PDE5 protein levels were unaffected by NO. The presence of PDE3
      or PDE5 in endothelial cells indicates that selective inhibitors may have
      functional effects in such cells. A complex interaction of cGMP and cAMP in
      response to NO administration may take place if the mRNA translates into active
      protein. Whether or not this plays a role in the headache mechanisms remains to
      be investigated.

PMID- 19751369
TI  - Headache and symptoms of temporomandibular disorder: an epidemiological study.
AB  - OBJECTIVES: A population-based cross-sectional study was conducted to estimate
      the prevalence of migraine, episodic tension-type headaches (ETTH), and chronic
      daily headaches (CDH), as well as the presence of symptoms of temporomandibular
      disorders (TMD) in the adult population. BACKGROUND: The potential comorbidity of
      headache syndromes and TMD has been established mostly based on clinic-based
      studies. METHODS: A representative sample of 1230 inhabitants (51.5% women) was
      interviewed by a validated phone survey. TMD symptoms were assessed through 5
      questions, as recommended by the American Academy of Orofacial Pain, in an
      attempt to classify possible TMD. Primary headaches were diagnosed based on the
      International Classification of Headache Disorders. RESULTS: When at least 1 TMD
      symptom was reported, any headache happened in 56.5% vs 31.9% (P < .0001) in
      those with no symptoms. For 2 symptoms, figures were 65.1% vs 36.3% (P < .0001);
      for 3 or more symptoms, the difference was even more pronounced: 72.8% vs 37.9%.
      (P < .0001). Taking individuals without headache as the reference, the prevalence
      of at least 1 TMD symptom was increased in ETTH (prevalence ratio = 1.48, 95%
      confidence interval = 1.20-1.79), migraine (2.10, 1.80-2.47) and CDH (2.41, 1.84
      3.17). At least 2 TMD symptoms also happened more frequently in migraine (4.4,
      3.0-6.3), CDH (3.4; 1.5-7.6), and ETTH (2.1; 1.3-3.2), relative to individuals
      with no headaches. Finally, 3 or more TMD symptoms were also more common in
      migraine (6.2; 3.8-10.2) than in no headaches. Differences were significant for
      ETTH (2.7 1.5-4.8), and were numerically but not significant for CDH (2.3; 0.66
      8.04). CONCLUSION: Temporomandibular disorder symptoms are more common in
      migraine, ETTH, and CDH relative to individuals without headache. Magnitude of
      association is higher for migraine. Future studies should clarify the nature of
      the relationship.

PMID- 19751370
TI  - Reduced adverse event profile of orally inhaled DHE (MAP0004) vs IV DHE:
      potential mechanism.
AB  - BACKGROUND: MAP0004 is a novel orally inhaled formulation of dihydroergotamine
      mesylate (DHE) currently in development that has been clinically observed to
      provide rapid ( approximately 10 minutes) therapeutic levels of DHE but with
      lower rates of adverse effects (dizziness, nausea, and paresthesia) compared with
      intravenous (IV) dosing. Receptor-based mechanistic studies were conducted to
      determine if differences between IV DHE and inhaled DHE (MAP0004) binding and
      functional activity were responsible for the improved adverse event profile.
      METHODS: Radioligand competitive binding assays were performed at adrenergic
      (alpha1 [non-specific], alpha2A, alpha2B, alpha2C, beta), dopaminergic (D; D(1),
      D(2), D(3)), and at serotonergic (5-HT; 5-HT(1A), 5-HT(1B), 5-HT(1D), 5-HT(2A), 5
      HT(2C), 5-HT(3), 5-HT(4), 5-HT(5A), 5-HT(6), 5-HT(7)) receptors. Binding assays
      were also conducted for the major metabolite of DHE, 8'-hydroxy-DHE (8'-OH-DHE).
      Subsequent functional receptor assays were also performed at 5-HT(1B), 5-HT(1D),
      5-HT(2A), 5-HT(2C), 5-HT(3), D(2), alpha1A, alpha2A, alpha2B, beta1, and beta2
      and muscarinic receptors to ensure that observed receptor binding translated into
      potential functional response. RESULTS: For competitive binding studies, DHE
      demonstrated extensive activity at IV C(max) for all 5-HT receptors tested,
      except 5-HT(3) and 5-HT(4), and alpha1, alpha2A, alpha2B, alpha2C, and D(3)
      receptors. DHE concentrations used in the studies were equal to the peak plasma
      concentrations (C(max)) observed in human subjects following IV DHE 1.0 mg (the
      standard approved dose), and 2 and 4 inhalations MAP0004 which, respectively,
      produced systemic circulation levels of DHE equivalent to 0.44 mg and 0.88 mg
      administered IV. MAP0004 binding activity at the C(max) concentrations was lower
      than IV DHE and no binding was observed for the 8'-OH-DHE metabolite. However,
      MAP0004 preserved potent agonist action at key anti-migraine 5-HT(1B) and 5
      HT(1D) receptors, even at the lower C(max )concentrations. Functional binding
      studies displayed similar results whereby IV DHE C(max) concentrations invoked
      strong agonist/antagonist responses, for instance at adrenergic and 5-HT(2C)
      receptors, which could have been responsible for dizziness. Conversely, at C(max)
      concentrations of MAP0004, inhaled DHE achieved a significantly lower response or
      no response at the adrenergic and 5-HT(2C) receptors. CONCLUSIONS: The mechanism
      by which nausea was experienced with IV DHE--yet not with MAP0004--was not
      associated with classic nausea pathways/targets (dopamine, 5-HT(3), or muscarinic
      receptors) or with peripheral action in the intestine via enterochromaffin cells.
      Importantly, the maximum DHE concentrations following MAP0004 administration were
      insufficient to interact with receptors implicated in cardiovascular (5-HT(2B)
      and beta(1)) and pulmonary effects (beta(2), adenosine, muscarinic, and
      leukotriene).

PMID- 19751371
TI  - Scheduled short-term prevention with frovatriptan for migraine occurring
      exclusively in association with menstruation.
AB  - OBJECTIVE: This post hoc subgroup analysis evaluated scheduled short-term
      preventive frovatriptan therapy for women with migraine occurring exclusively in
      association with menstruation (occurring day -2 to +3; day 1 = menses start, no
      migraines outside this window). BACKGROUND: A previously published randomized,
      double-blind, placebo-controlled 3-way crossover trial assessed the efficacy and
      safety of a scheduled 6-day preventive regimen with frovatriptan for the
      treatment of menstrual migraine; the study population included women experiencing
      both menstrual and non-menstrual migraine and women experiencing only menstrual
      migraine. METHODS: Women received each treatment (placebo, frovatriptan 2.5 mg
      once daily, and frovatriptan 2.5 mg twice daily) once over 3 perimenstrual
      periods in randomized sequence. For this subset analysis, screening questions
      were used to identify women with migraine occurring exclusively in association
      with menstruation. Efficacy was evaluated by occurrence and severity of migraine,
      functional impairment, and rescue medication use. Adverse events and tolerability
      were also assessed. RESULTS: Among 179 patients, the mean age (SD) was 37.3 (7.7)
      years and mean menstrual migraine history was 10.6 (8.7) years. Significantly
      fewer women experienced menstrual migraine during treatment with frovatriptan
      twice daily (37.7%, P < .001) or once daily (51.3%, P = .002) than during
      treatment with placebo (67.1%); a significant dose response was noted (P = .01,
      twice daily vs once daily). Significant treatment differences were also found for
      several secondary endpoints, but the data from this post hoc analysis must be
      interpreted with caution. Frovatriptan was well tolerated and most adverse events
      were mild or moderate and similar to those reported with the acute treatment of
      migraine with frovatriptan; the most common adverse events were nausea,
      dizziness, and headache. CONCLUSIONS: Scheduled short-term preventive
      frovatriptan therapy effectively reduced the occurrence of menstrual migraine in
      women with attacks occurring exclusively in association with menstruation.

PMID- 19751372
TI  - Bezold's abscess: a serious complication of otitis media.
AB  - This report describes a case of Bezold's abscess, a rare complication of
      mastoiditis, following otitis media. Included is a discussion of mastoiditis and
      its management.

PMID- 19751373
TI  - Lower genital tract lesions requiring surgical intervention in girls: perspective
      from a developing country.
AB  - AIM: To determine the spectrum, outcome of treatment and the challenges of
      managing surgical lesions of lower genital tract in girls in a low-resource
      setting. METHOD: Retrospective study of 87 girls aged 13-years and younger, with
      lower genital tract lesions managed between February 2002 and January 2007 at the
      University of Nigeria Teaching Hospital, Enugu, southeastern Nigeria. Clinical
      charts were reviewed to determine the types, management, outcome of treatment and
      management difficulties. RESULTS: The median age at presentation was 1 year
      (range 2 days-13 years). Congenital lesions comprised 67.8% and acquired lesions
      32.2%. The lesions included: masculinized external genitalia (24), vestibular
      fistula from anorectal malformation (23), post-circumcision labial fusion (12),
      post-circumcision vulval cyst (6), low vaginal malformations (6), labial adhesion
      (5), cloacal malformation (3), bifid clitoris (3) urethral prolapse (3), and
      acquired rectovaginal fistula (2). Seventy-eight (89.7%) had operative treatment.
      Procedure related complications occurred in 19 cases (24.4%) and consisted of
      surgical wound infection (13 cases), labial adhesion (4 cases) and urinary
      retention (2 cases). There was no mortality. Overall, 14 (16.1%) abandoned
      treatment at one stage or another. Challenges encountered in management were
      inadequate diagnostic facilities, poor multidisciplinary collaboration and poor
      patient follow up. CONCLUSION: There is a wide spectrum of lower genital lesion
      among girls in our setting. Treatment of these lesions may be challenging, but
      the outcome in most cases is good. High incidence of post-circumcision
      complications and poor treatment compliance may require more efforts at public
      enlightenment.

PMID- 19751374
TI  - Immunisation practices in infants born prematurely: neonatologists' survey and
      clinical audit.
AB  - AIM: To determine Australian neonatologists' recommendations for the immunisation
      of ex-preterm infants and compare their actual immunisation status with
      recommended Australian guidelines. METHODS: A self-administered nine-part
      questionnaire of current immunisation practices was sent to all Neonatologists in
      Australia (2006). A complementary retrospective immunisation audit was conducted
      in two tertiary neonatal units in Melbourne. Hospital records and the Australian
      Childhood Immunisation Register (ACIR) were reviewed; consenting parents were
      interviewed and primary care physicians' vaccination records were requested. A
      random sample of preterm infants born between July 2003 and June 2005 at <32
      weeks' gestation were selected. RESULTS: (i) Neonatologists Survey: The response
      rate was 68% and the majority of neonatologists (89%) were aware of the current
      guidelines, but adherence to them varied from 43% to 79%. One-fifth of
      neonatologists personally do not receive annual influenza vaccination; and (ii)
      Immunisation Audit: Conducted between October 2006-May 2007 it included: 100
      hospital records; 97 ACIR records; 47 parent interviews and 43 primary care
      vaccination records. Overall vaccination coverage was 90% at 12 months of age.
      Only 20% (10/50) of infants with chronic lung disease received an influenza
      vaccination. Vaccines were delayed by greater than one month in 15% of
      participants for the 2 month DTPa vaccine and 43% at 6 months. CONCLUSIONS: The
      neonatologists survey highlighted variable adherence with immunisation
      guidelines. The audit confirmed preterm infants are frequently experiencing
      delayed vaccination and recommended additional vaccinations are often not being
      received. Formulation of strategies to ensure complete and timely immunisation
      are required, including better utilisation of the ACIR.

PMID- 19751375
TI  - Risks of severity and readmission of Indigenous and non-Indigenous children
      hospitalised for bronchiolitis.
AB  - OBJECTIVE: To describe the characteristics of children admitted to Royal Darwin
      Hospital with bronchiolitis, and to compare the severity of illness and incidence
      of subsequent readmission in Indigenous and non-Indigenous children. DESIGN,
      SETTING AND PARTICIPANTS: Retrospective study of 101 children (aged <or=2 years)
      hospitalised with bronchiolitis to Royal Darwin Hospital between April 2005 and
      December 2006. MAIN OUTCOME MEASURES: Admission characteristics and indices of
      severity, treatment required (antibiotics etc.), reasons and incidence of
      readmissions (within 6 months). RESULTS: Indigenous children had significantly
      more severe illness then non-Indigenous children (n= 80 and 21, respectively),
      longer hospital stay (median = 6 and 3 days; P= 0.001) and oxygen requirement
      (median = 3 and 0; P= 0.004), pneumonia (n= 14 and 0; P= 0.04) and antibiotics
      treatment (48 and 4; P= 0.001). The readmission rate for bronchiolitis was high
      (23%) with no significant difference between Indigenous and non-Indigenous
      children. CONCLUSION: Indigenous Australian children hospitalised with
      bronchiolitis have significantly more severe illness than non-Indigenous
      children. Points of intervention that can address this and the identified high
      readmission rate (within 6 months) are required.

PMID- 19751376
TI  - Caffeine versus theophylline for apnea of prematurity: a randomised controlled
      trial.
AB  - AIM: To compare standard doses of theophylline and caffeine for apnea of
      prematurity in terms of apnea frequency and assess the need for therapeutic drug
      monitoring. METHODS: Seventy neonates less than 33 weeks gestation, breathing
      spontaneously, were randomly assigned (open-label) to receive either theophylline
      or caffeine for treatment or prevention of apnea. The primary outcome measure was
      the difference in apnea frequency between theophylline and caffeine patient
      groups. Methylxanthine serum levels were measured on the 1st, 3rd and 7th days of
      therapy and every 7 days thereafter. RESULTS: Thirty-seven neonates received
      theophylline (T) and 33 caffeine (C) for treatment (8 T/10 C) or prevention of
      apnea (29 T/23 C). Treatment with either methylxanthine significantly decreased
      apnea events (T, P= 0.012; C, P= 0.005) while only C prophylaxis appeared to
      control apnea in infants at risk. Analysis of combined (treatment plus
      prophylaxis) data showed a significant decrease in apnea frequency only in those
      infants receiving caffeine (P= 0.001). However, there was no sustained benefit of
      C over T beyond the first week of therapy. T and C concentrations (2.2-13.9 mg/L;
      5.5-23.7 mg/L, respectively) in the majority of cases fell within the recommended
      therapeutic ranges and were not significantly associated with apnea events.
      CONCLUSIONS: This study shows an advantage of C over T for premature infants <33
      weeks gestation during the first week of therapy. Standard regimens of both
      methylxanthines do not seem to require routine concentration monitoring in the
      first 3 weeks of treatment unless indicated by clinical effect.

PMID- 19751377
TI  - The influence of skin temperature and skin perfusion on the cephalocaudal
      progression of jaundice in newborns.
AB  - AIM: Despite being widely recognized, the cephalocaudal progression of jaundice
      in newborns (Kramer's Rule) has never been satisfactorily explained. The aim of
      this study was to test the hypothesis that the cephalocaudal progression of
      jaundice in newborns is related to regional differences in skin temperature and
      skin perfusion. METHODS: A convenience sample of 50 infants was included in the
      study. On each infant, a transcutaneous bilirubin, skin temperature and capillary
      refill time measurement was made at five sites; the forehead, sternum, lower
      abdomen, mid thigh and sole. The relationship between the three variables was
      studied by analysis of variance. RESULTS: The transcutaneous bilirubin
      measurements upheld Kramer's observation, being significantly higher at the head
      and chest than at the thigh and sole (P < 0.001). A similar pattern was found for
      both skin temperature and capillary refill, both significantly different at the
      head compared to the sole (P < 0.001). CONCLUSION: The results of the study
      support the hypothesis that the cephalocaudal progression of jaundice in newborns
      is a consequence of diminished capillary blood flow in distal parts of the body.
      It is hypothesized that newborn infants preferentially perfuse their head and
      proximal parts of their body in the first few days of life, leading to higher
      temperatures and increased bilirubin deposition at these sites.

PMID- 19751378
TI  - Evaluation of a feasibility study addressing risk factors for childhood obesity
      through home visits.
AB  - AIM: This pilot study aimed to explore the feasibility of addressing risk factors
      for childhood obesity through a home-based early intervention program. METHOD: A
      pilot study was conducted with 56 first-time mothers, recruited through the
      antenatal and delivery units of an inner western Sydney hospital. The study
      offered five home visits by a community early childhood health nurse during the
      child's first year of life. At each visit, the intervention was tailored to the
      appropriate developmental stage of the child. One-to-one consultation was
      provided with a focus on sustained breastfeeding, appropriate introduction of
      solids, avoiding food rewards and promoting the drinking of water and the use of
      a cup. Both quantitative and qualitative methods were applied to assess the
      feasibility and acceptability of the program. RESULTS: The results indicate that
      the program was very well received by the participating mothers, with a retention
      rate of 95%. Compared with the state population average, the rate of
      breastfeeding at 12 months was significantly higher (36% vs. 18%, chi(2)= 8.21, P
      < 0.01), there was a lower rate of the introduction of solids before 4 months (2%
      vs. 13%, chi(2)= 8.73, P < 0.01), and there was a high rate of cup usage at 12
      months (98%). CONCLUSIONS: The early onset of childhood overweight and obesity
      requires health promotion intervention programs to commence as early as possible.
      A home-based intervention through multiple home visits is feasible in addressing
      the risk factors for childhood obesity.

PMID- 19751379
TI  - Consulting parents on childhood obesity and implications for medical student
      learning.
AB  - AIM: It is important that medical schools take some account of community
      expectations for health care when planning curricula. This is particularly
      important for emerging public health problems such as childhood obesity. The aim
      of this study was to explore parent attitudes to the role of the doctor in
      childhood obesity and implications for medical student learning. METHODS: The
      views of eight mothers and one father were explored through interview.
      Transcripts were analysed using an iterative process of theme identification and
      testing against transcript data. A range of recruitment strategies were used in
      an attempt to increase participant numbers. RESULTS: Participants believed
      doctors should support parent decisions about children's diet and life-style and
      be prepared to 'step-in' with a more active role when, in the parent's view, this
      was needed. Participants wanted doctors to provide advice on healthy nutrition,
      be proficient in child physical assessment and be able to communicate sensitively
      with both children and parents. CONCLUSION: Although the parents who agreed to be
      interviewed expressed views demonstrating their commitment to preventing and
      reducing childhood obesity, many other parents declined the invitation to
      contribute. It may be that parent concern within the broader community that
      childhood obesity is a real and significant health risk does not reflect the
      level of concern of the medical profession. The most likely implications for the
      teaching of medical students are a need for more comprehensive teaching around
      healthy diet and activity for all children, improved recognition of overweight
      and obesity and ongoing communication skills development.

PMID- 19751380
TI  - Lactic acid bacteria population in children diagnosed with human immunodeficiency
      virus.
AB  - AIM: To determine the effect of trimethoprim/sulphamethoxazole treatment on the
      natural population of lactic acid bacteria in the intestinal tract and to
      determine if any of the strains developed resistance to antibiotics. METHODS:
      Lactic acid bacteria were isolated from stool samples of 100 children. The
      isolates were identified based on biochemical characteristics and DNA profiles
      obtained from polymerase chain reaction with genus- and species-specific primers.
      Resistance to sulphamethoxazole, streptomycin, compound sulphonamides,
      chloramphenicol and vancomycin was tested using the paper-disk method. RESULTS:
      The lactic acid bacteria were identified as Lactobacillus acidophilus,
      Lactobacillus brevis, Lactobacillus paracasei, Lactobacillus pentosus,
      Lactobacillus rhamnosus, Leuconostoc mesenteroides subsp. mesenteroides,
      Enterococcus spp. and Weissella spp. Lactobacillus plantarum and Bifidobacterium
      spp. were not isolated. All strains, except two, were sensitive to
      chloramphenicol and streptomycin. Thirty-five percent of the isolates were
      resistant to vancomycin, 50% to compound sulphonamides and 66% to
      sulphamethoxazole. CONCLUSION: Treatment with trimethoprim/sulphamethoxazole
      repressed a large number of lactic acid bacteria normally present in the
      intestinal tract of children. A number of strains were resistant to
      sulphamethoxazole and may be used as probiotics to correct the imbalance in
      lactic acid bacteria.

PMID- 19751381
TI  - Catheter balloon-related urethral trauma in children.
AB  - AIM: To review urethral injuries arising from incorrect balloon inflation in
      children undergoing urinary catheterisation. METHOD: Retrospective review from
      1995-2006. Children who sustained catheter-related injury at The Children's
      Hospital at Westmead were identified through medical records database and
      reviewed. RESULTS: Six patients were identified over the 11-year period. All six
      were boys. Age ranged from <1 month to 16 years. All but one occurred in
      hospital. All injuries were confirmed by urethrogram. Bulbar and prostatic
      urethra was involved in an equal number of children studied. Three patients
      required suprapubic catheters. Follow-up imaging revealed healing without
      stricture in all patients. CONCLUSION: Balloon-related urethral trauma can be
      avoided by educating health-care professionals on proper placement and
      confirmation of position of catheter. Though there were no long-term
      complications noted, a temporary suprapubic diversion may be needed.

PMID- 19751382
TI  - Management of children with otitis media: a summary of evidence from recent
      systematic reviews.
AB  - Health-care professionals who manage children are regularly confronted with
      clinical questions regarding the management of the full spectrum of otitis media:
      acute otitis media; otitis media with effusion; and chronic suppurative otitis
      media. Given the variety of potential therapies available, the wide spectrum of
      middle ear disorders, and the lack of consensus about management strategies,
      clinicians are in a difficult position when managing these children. In this
      review, we seek to summarise the current best evidence for answering otitis media
      management questions by collating existing systematic reviews.

PMID- 19751383
TI  - Musculoskeletal pain and sexual function in women.
AB  - INTRODUCTION: Sexual pain disorders refer to conditions of genital pain that
      interfere with intercourse. They often have a musculoskeletal component related
      to the pelvic floor and are included in the DSM-IV as sexual dysfunctions.
      Musculoskeletal pain (MP) that is not essentially genitally based often
      interferes with sex as well yet is not considered a distinct sexual dysfunction.
      MP is generally addressed by physiatrists, orthopedists, and rheumatologists who
      are not traditionally trained in sexual medicine, and therefore, the sexual
      concerns of women with MP often go unaddressed. AIM: The purposes of this review
      article were to describe how MP is perceived in the literature as affecting
      sexual function, illustrate how specific MP conditions prevalent in women may
      affect sexual function, and offer recommendations for clinical practice. METHODS:
      PubMed and Medline searches were performed using the keywords "musculoskeletal
      pain and sex,""lower back pain and sex,""arthritis and sex," and "fibromyalgia
      and sex". Main Outcome Measure. Review of the peer-reviewed literature. RESULTS:
      Most studies cite fatigue, medication, and relationship adjustment as affecting
      sexuality much as chronic illness does. While musculoskeletal contributors to
      genital sexual response and pain are considered relevant to sexual function,
      little is understood about how MP syndromes specifically affect sexual activity.
      CONCLUSION: Lack of mobility and MP can restrict intercourse and limit sexual
      activity, and gender differences are noted in response to pain. Sexual and
      relationship counseling should be offered as a component of rehabilitative
      treatment. Physical therapists are uniquely qualified to provide treatment to
      address functional activities of daily living, including sexual intercourse, and
      offer advice for modifications in positioning.

PMID- 19751384
TI  - Sexual motivation in women as a function of age.
AB  - INTRODUCTION: Women's motivations to engage in sex are likely influenced by their
      past sexual experiences, the type of relationship in which they are involved in,
      and numerous lifestyle factors such as career and family demands. The influences
      of these factors undoubtedly change as women age. AIM: This study aimed to
      examine potential differences in sexual motivation between three distinct age
      groups of premenopausal women. METHODS: Women aged 18-22 years (N = 137), 23-30
      years (N = 103), and 31-45 years (N = 87) completed an online survey that
      assessed the proportion with which they had engaged in sexual intercourse for
      each of 140 distinct reasons. MAIN OUTCOME MEASURES: The YSEX? Questionnaire by
      Meston and Buss [1] was used to measure sexual motivation. The items of this
      questionnaire were composed of four primary sexual motivation factors (physical,
      goal attainment, emotional, insecurity), and 13 subfactors. RESULTS: Women aged
      31-45 years reported a higher proportion of engaging in sex compared with one or
      both of the younger age groups of women for nine of the 13 YSEX? subfactors:
      stress reduction, physical desirability, experience seeking, resources, social
      status, revenge, expression, self-esteem boost, and mate guarding. At an item
      level, the top 25 reasons for having sex were virtually identical across age
      groups. CONCLUSION: Women aged 31-45 have more motives for engaging in sex than
      do women aged 18-30, but the primary reasons for engaging in sex do not differ
      within this age range. Women aged 18-45 have sex primarily for pleasure, and love
      and commitment. The implications for diagnosis and treatment of women with sexual
      dysfunctions were discussed.

PMID- 19751385
TI  - Correlates of sexuality in men and women aged 52-90 years attending a university
      medical health service in Colombia.
AB  - INTRODUCTION: Limited information is available regarding sexuality among
      Colombian adults aged 50 years and older. AIM: To assess demographic or health
      characteristics associated with sexuality measures among middle- and older-aged
      men and women. METHODS: Cross-sectional face-to-face interviews were conducted
      with retired persons from a university ambulatory medical care setting. Data on
      sexuality were obtained along with data on their demographic, emotional intimacy,
      practice of religion, medical conditions, and functional health measures. There
      were 136 participants. MAIN OUTCOME MEASURES: Appropriateness of sex, sexual
      desire, importance of sex, masturbation, and sexual intercourse. RESULTS: Fifty
      seven percent of the participants were over 65 years of age, 52% were female, and
      66% reported being married; 67% indicated sex is appropriate, 58% reported having
      sexual desire, 45% considered sex very important in their lives, 54% reported one
      or more instances of sexual intercourse, and 16% reported masturbating within the
      last year. In multivariate analyses, importance of sex and sexual intercourse
      decreased by age. Women had decreased odds ratios (0.20 to 0.33) for sexuality
      measures compared with men with the exception of appropriateness of sex. Married
      persons had increased odds ratios (3.06 to 9.45) for importance of sex,
      appropriateness of sex, and sexual intercourse compared with those of the same
      age who reported being unmarried. Other factors associated with some particular
      sexuality measures were emotional intimacy, religious practice, medical
      conditions, and functional health measures. There were significant mediation
      effects for appropriateness of sex on the relationship between sexual desire and
      sexual intercourse, and for importance of sex on the relationship between
      appropriateness of sex and sexual intercourse. CONCLUSIONS: Men and married
      persons had higher rates of most sexuality measures compared with women or their
      unmarried counterparts. These differences were greater at older ages (> or =65)
      for all sexuality measures except sexual intercourse.

PMID- 19751386
TI  - Clinical parameters that predict successful outcome in men with premature
      ejaculation and inflammatory prostatitis.
AB  - INTRODUCTION: Premature ejaculation (PE) is the most common sexual problem, and
      chronic prostatitis is an important cause of PE. AIM: The aim of this study was
      to determine which clinical parameters predict successful outcomes following
      treatment of men with PE and chronic prostatitis (category II and IIIa). MAIN
      OUTCOME MEASURE: Change in intravaginal ejaculatory latency time (IELT) and its
      relation to different clinical parameters. METHODS: This study included 210
      heterosexual men with PE and inflammatory prostatitis. PE was found to be
      acquired in 155 men (A-PE) and lifelong in 55 (LL-PE). All participants were
      asked to complete the National Institutes of Health-Chronic Prostatitis Symptom
      Index (NIH-CPSI). Sequential microbiologic specimens were obtained. Antibiotics
      were given to 184 men for 4 weeks, guided by sensitivity tests. Twenty-six men
      refused or did not comply with the antimicrobial therapy and were used as the
      untreated group. Clinical reevaluation was conducted after 28 days. RESULTS: Two
      of the 26 men (7.7%) from the untreated group experienced an increase in their
      ejaculatory latency compared with 109 of the 184 men (59.0%) who received
      antimicrobial therapy (P = 0.0001). After treatment, 90 of 155 men (58.0%) with A
      PE reported ILET > 2 minutes compared with 21 of 55 men (38.2%) with LL-PE (P =
      0.012). Based on a receiver operating characteristic curve, antimicrobial therapy
      is most effective if there are > or =19 pus cells per high-power field (HPF) in
      the expressed prostatic secretion (EPS) analysis, with a sensitivity of 85.6% and
      a specificity of 70.7% (area under the curve 0.783, 95% CI 0.716-0.850). Other
      clinical parameters were not useful in predicting outcomes. CONCLUSIONS:
      Antimicrobial therapy is useful in the treatment of PE associated with
      inflammatory prostatitis. The treatment is most effective in men with A-PE and
      when there are > or =19 pus cells per HPF in an EPS analysis.

PMID- 19751387
TI  - Factors affecting self-reported sexuality in men with obstructive sleep apnea
      syndrome.
AB  - INTRODUCTION: Obstructive sleep apnea syndrome (OSAS) is known to induce erectile
      dysfunction and to reduce overall sexual satisfaction in affected men. Data on
      the effects of disease severity and other contributing factors such as the age of
      the patient are missing. AIM: To compare self-reported sexuality in men with
      newly diagnosed sleep apnea with a group of disease-free men, and to evaluate the
      impact of disease severity and age on the response pattern. MAIN OUTCOME
      MEASURES: Self-reported erectile function, desire, and frequencies for petting,
      tenderness, masturbation, sexual intercourse, and overall satisfaction with
      sexuality over a recall period of 3 months. METHODS: A prospective survey in men
      admitted to a multidisciplinary sleep center using a standardized validated
      German questionnaire. RESULTS: One hundred-sixteen men 51.1 +/- 11.4 years (mean
      +/- standard deviation) with OSAS (OSAS+) and 42 men age 46.6 +/- 13.7 years
      without OSAS (OSAS-) completed the survey. OSAS+ men were older (P = 0.01) and
      more often divorced (P = 0.048). OSAS was significantly associated with erection
      problems (P = 0.024) and decreased overall sexual satisfaction (P = 0.04). In
      contrast disease severity did affect masturbation frequency only (P = 0.02),
      whereas patient age affected erection (P = 0.001), and the desire for tenderness
      (P = 0.02) and intercourse (P = 0.0003). CONCLUSION: Patient age might be a more
      important factor affecting sexuality in men with sleep apnea than the disease
      severity. Future studies assessing sexuality in men with OSAS should include age
      as an additional variable.

PMID- 19751388
TI  - Are sadomasochism and hypersexuality in autism linked to amygdalohippocampal
      lesion?
AB  - INTRODUCTION: Pathologies of the amygdala and the hippocampus have been argued to
      be critically involved in autism as well as in sadomasochism. In line with Kluver
      and Bucy syndrome, clinical observations, animal models and a few case reports
      emphasize that temporal brain changes are important for the etiopathogenesis of
      sexual deviant behaviour. In particular, the amygdalohippocampal region has been
      linked to hypersexuality, transvestitism and fetishism. While cases and studies
      are rare, the impact of amygdalohippocampal changes in criminal behaviour remains
      unclear so far. AIM: To demonstrate the impact of subcortical neurobiological
      changes in the etiopathogenesis of autism and sadomasochism. METHODS: We report
      on a forensic psychiatric inpatient due to murderer with autism and sadomasochism
      who had amgdalohippocampal abnormalities bilaterally. Studies on the
      neurobiological underpinnings of autism and of sadomasochism are reviewed in
      particular regarding amygdalohippocampal region. RESULTS: In this patient, MRI
      scan showed hypointensities in amygdala-hippocampal complex bilaterally medial to
      both cornua inferiores corresponding to an amygdalo-hippocampal atrophy.
      CONCLUSIONS: In line with the literature, this case report links autism and
      sadomasochism to amygdalohippocampal pathology emphasising its impact in the
      etiopathogenesis of both disorders. Further research is needed to elucidate the
      interaction of amygdalohippocampal changes, disturbed emotion precessing and sex
      offenses.

PMID- 19751389
TI  - Neuroimaging differences in spatial cognition between men and male-to-female
      transsexuals before and during hormone therapy.
AB  - INTRODUCTION: Neuropsychological abnormalities in transsexual patients have been
      reported in comparison with subjects without gender identity disorder (GID),
      suggesting differences in underlying neurobiological processes. However, these
      results have not consistently been confirmed. Furthermore, studies on cognitive
      effects of cross-sex hormone therapy also yield heterogeneous results. AIM: We
      hypothesized that untreated transsexual patients differ from men without GID in
      activation pattern associated with a mental rotation task and that these
      differences may further increase after commencing of hormonal treatment. METHOD:
      The present study investigated 11 male-to-female transsexual (MFTS) patients
      prior to cross-sex hormone therapy and 11 MFTS patients during hormone therapy in
      comparison with healthy men without GID. Using functional magnetic resonance
      imaging at 3-Tesla, a mental rotation paradigm with proven sexual dimorphism was
      applied to all subjects. Data were analyzed with SPM5. MAIN OUTCOME MEASURES:
      Patterns of brain activation associated with a mental rotation task. RESULTS: The
      classical mental rotation network was activated in all three groups, but
      significant differences within this network were observed. Men without GID
      exhibited significantly greater activation of the left parietal cortex (BA 40), a
      key region for mental rotation processes. Both transsexual groups revealed
      stronger activation of temporo-occipital regions in comparison with men without
      GID. CONCLUSIONS: Our results confirmed previously reported deviances of brain
      activation patterns in transsexual men from men without GID and also corroborated
      these findings in a group of transsexual patients receiving cross-sex hormone
      therapy. The present study indicates that there are a priori differences between
      men and transsexual patients caused by different neurobiological processes or
      task-solving strategies and that these differences remain stable over the course
      of hormonal treatment.

PMID- 19751390
TI  - Unsuccessful investigation of preoperative sexual health issues in the prostate
      cancer "couple": results of a real-life psychometric survey at a major tertiary
      academic center.
AB  - INTRODUCTION: Investigating preoperative sexual function of patients with
      prostate cancer (PCa) and their partners is needed for realistic functional
      outcome analyses after radical prostatectomy (RP). AIM: To assess pre-RP sexual
      health issues of PCa patients and their partners in a stable heterosexual
      relationship. METHODS: Data were analyzed from 3,282 consecutive patients who
      underwent RP over a three-period survey. During Period 1, on admission to the
      hospital the day prior to surgery, 1,360 patients were asked to complete the
      International Index of Erectile Function (IIEF). During Period 2, 1,171 patients
      were asked to complete the preoperative IIEF; similarly, patients' partners were
      invited to complete the Female Sexual Function Index (FSFI). Lastly, during
      Period 3, only candidates for RP were asked to fill in the IIEF. MAIN OUTCOME
      MEASURES: To assess the rate of patients who completed the questionnaire during
      the three-period survey. To detail the proportion of patients' partners who
      filled in the questionnaire, along with the partners' reasons for non-adherence
      to the proposed investigation during Period 2. RESULTS: A small rate of men
      completed the IIEF during Period 1 (583 in 1,360 [42.9%]), Period 2 (290 in 1,171
      [24.8%]), and Period 3 (261 in 751 [34.8%]) (chi(2) trend: 13.06; P = 0.0003). In
      this context, a significantly lower proportion of patients completed the
      questionnaire during Period 2, as compared with both Period 1 (chi(2): 95.13; P =
      0.0001) and Period 3 (chi(2): 21.87; P < 0.0001). Only 82 in 1,171 (7.0%)
      partners completed the FSFI over Period 2. Moreover, only 6 in 82 (7.3%) of women
      provided complete data. CONCLUSIONS: The investigation of sexual health issues of
      both partners prior to RP is largely unsuccessful. In this context, the
      prevalence of incomplete data collection is high, and these results demonstrate
      that contemporaneously investigating the sexual health issues of both partners
      significantly increases the prevalence of incomplete data collection.

PMID- 19751391
TI  - Ginsenoside Rg1 improves male copulatory behavior via nitric oxide/cyclic
      guanosine monophosphate pathway.
AB  - INTRODUCTION: Ginsenoside Rg1 is the purified ingredient from ginseng, there has
      been little research on the effect of Rg1 on male copulatory behavior and its
      mechanism of action. AIM: The purpose of this study was to investigate the effect
      of ginsenoside Rg1 on copulatory behavior of male mice and the mechanism of its
      action. METHODS: Male mice were treated with Rg1 intraperitoneally; three
      elements of copulatory behavior (mounting, intromission, pelvic thrusting) were
      assessed. After final treatment and behavior determination, nitric oxide (NO)
      concentration were determined by spectrophotometry method. Plasma testosterone,
      cyclic guanosine monophosphate (cGMP) in corpus cavernosum both in vivo and in
      vitro were measured by radioimmunoassay. Rabbit corpus cavernosum segments were
      incubated with Rg1 (0.05, 0.5 and 5 microM) in the presence of exogenous NO donor
      sodium nitroprusside (SNP) (10 microM), and the cGMP level was measured. The half
      maximal inhibitory concentration (IC50) of Rg1 for phosphodiesterase type 5
      (PDE5) inhibitors was determined by measuring the conversion of cGMP to 5'
      mononucleotides. Sildenafil was set as a positive control. MAIN COME OUT
      MEASURES: Mounting and intromission frequency, pelvic thrusts, serum
      testosterone, NO level, cGMP accumulation, IC50 for PDE5. RESULTS: Rg1 (10 mg/kg)
      significantly increased mounting and pelvic thrusting frequency and numbers of
      intromission of male mice from d16 to d20. Rg1 increased serum testosterone
      concentration, enhanced NO release, and cGMP accumulation in corpus cavernosum
      both in vivo and in vitro. The IC50 of sildenafil and Rg1 for PDE5 were 4.24 +/-
      0.78 and 12.47 +/- 2.31 nmol/L. CONCLUSIONS: Ginsenoside Rg1 improved copulatory
      behavior of male mice and this may attribute to its actions at both testosterone
      level and signal transduction pathway in corpus cavernosum. NO/cGMP pathway
      appeared to play a key role in mediating the effect of Rg1 on male sexual
      function. These experimental data provide evidence that Rg1 could be a promising
      new drug for erectile dysfunction and low libido.

PMID- 19751392
TI  - Fusarium solani onychomycosis of the thumbnail coinfected with Pseudomonas
      aeruginosa: report of two cases.
AB  - Fusarium species are non-dermatophytic moulds, which are commonly known soil
      saprophytes and important plant pathogens, and have been frequently reported to
      be aetiological agents of opportunistic infections in humans. The prevalence of
      onychomycosis caused by Fusarium species varies in the literature because of
      geographical differences in mould distribution and diagnostic methods.
      Onychomycosis caused by Fusarium species is considered rare in Korea, and only
      four cases have been described to date. Pseudomonas aeruginosa also can infect
      nails and cause green nail syndrome, and recent research has shown that fungal
      infection may potentiate the colonisation or growth of P. aeruginosa within a
      nail. Furthermore, such coinfection with P. aeruginosa can prevent the isolation
      of the fungus because of bacterial overgrowth in culture. The authors report the
      cases of two immunocompetent patients with F. solani onychomycosis coinfected
      with P. aeruginosa. Both presented with a greenish/yellowish discolouration and
      thickening of a thumbnail, and were treated with systemic ciprofloxacin in
      combination with itraconazole or terbinafine.

PMID- 19751393
TI  - Transactivation activity of LBP-1 proteins and their dimerization in living
      cells.
AB  - LBP-1 proteins form dimers and act as transcription factors that activate a
      number of genes related to cell growth and differentiation. LBP-1a and LBP-1c are
      localized in the cytoplasm when transiently expressed in cultured cells, but
      translocated into the nucleus after forming heterodimers with LBP-1b, which is a
      splicing variant of LBP-1a with an intrinsic nuclear localization signal (NLS).
      Here, we report that LBP-1b showed potent transactivation activity, and that
      forcibly expressed LBP-1a and LBP-1c in the nucleus essentially exhibited very
      little or no transactivation activity. Mutations in the NLS that abolished the
      NLS activity of LBP-1b also abrogated the transactivation activity. We have found
      that LBP-1 proteins contain a putative sterile alpha motif domain indispensable
      for their dimerization capability in the C-terminal region. To demonstrate
      whether homo- and heterodimers composed of LBP-1a and/or LBP-1c are generated in
      the nucleus, we applied the FLIM-based fluorescence resonance energy transfer
      imaging technique to living cells. It revealed that dimers composed of LBP-1a and
      LBP-1c were re-formed probably by a partner-exchange of LBP-1b-containing
      heterodimers.

PMID- 19751395
TI  - Identifying emotional adaptation: behavioural habituation to novelty and
      immediate early gene expression in two inbred mouse strains.
AB  - Normal anxiety is an adaptive emotional response. However, when anxiety appears
      to lack adaptive value, it might be defined as pathological. Adaptation in
      animals can be assessed for example by changes in behavioural responses over
      time, i.e. habituation. We hypothesize that non-adaptive anxiety might be
      reflected by impaired habituation. To test our hypothesis, we repeatedly exposed
      male mice from two inbred strains to a novel environment, the modified hole
      board. BALB/cJ mice were found to be initially highly anxious, but subsequently
      habituated to the test environment. In contrast, 129P3/J mice initially showed
      less anxiety-related behaviour compared with the BALB/cJ mice but no habituation
      in anxiety-related behaviour was observed. Notably, anxiety-related behaviour
      even increased during the experimental period. Complementary, 129P3/J mice did
      not show habituation in other parameters such as locomotor and exploratory
      activity, whereas significant changes appeared in these behaviours in BALB/c
      mice. Finally, the expression of the immediate early gene c-fos differed between
      the two strains in distinct brain areas, known to regulate the integration of
      emotional and cognitive processes. These results suggest that 129P3/J mice might
      be a promising (neuro)-behavioural animal model for non-adaptive, i.e.
      pathological anxiety.

PMID- 19751394
TI  - Genetic loss of D-amino acid oxidase activity reverses schizophrenia-like
      phenotypes in mice.
AB  - Reduced function of the N-methyl-d-aspartate receptor (NMDAR) has been implicated
      in the pathophysiology of schizophrenia. The NMDAR contains a glycine binding
      site in its NR1 subunit that may be a useful target for the treatment of
      schizophrenia. In this study, we assessed the therapeutic potential of long-term
      increases in the brain levels of the endogenous NMDAR glycine site agonist D
      serine, through the genetic inactivation of its catabolic enzyme D-amino acid
      oxidase (DAO) in mice. The effects of eliminating DAO function were investigated
      in mice that display schizophrenia-related behavioral deficits due to a mutation
      (Grin 1(D481N)) in the NR1 subunit that results in a reduction in NMDAR glycine
      affinity. Grin 1(D481N) mice show deficits in sociability, prolonged latent
      inhibition, enhanced startle reactivity and impaired spatial memory. The
      hypofunctional Dao 1(G181R) mutation elevated brain levels of D-serine, but alone
      it did not affect performance in the behavioral measures. Compared to animals
      with only the Grin 1(D481N) mutation, mice with both the Dao1(G181R) and Grin
      1(D481N) mutations displayed an improvement in social approach and spatial memory
      retention, as well as a reversal of abnormally persistent latent inhibition and a
      partial normalization of startle responses. Thus, an increased level of D-serine
      resulting from decreased catalysis corrected the performance of mice with
      deficient NMDAR glycine site activation in behavioral tasks relevant to the
      negative and cognitive symptoms of schizophrenia. Diminished DAO activity and
      elevations in D-serine may serve as an effective therapeutic intervention for the
      treatment of psychiatric symptoms.

PMID- 19751396
TI  - Activity and impulsive action are controlled by different genetic and
      environmental factors.
AB  - Both impulsivity in operant tasks and locomotor activity in a novel open field
      are known to predict the development of addiction-related behavior in rodents. In
      this study, we investigated to what extent impulsivity in the five-choice serial
      reaction time task and various measures of novelty exploration are controlled by
      shared genetic and environmental factors in 12 different inbred mouse strains. No
      genetic correlation was observed between the level of impulsivity and levels of
      activity, a low correlation was observed with traditional measures of anxiety
      like behavior (impulsive strains tend to be less anxious) and a highly
      significant correlation was found between impulsivity and specific aspects of
      movement. Furthermore, we found that impulsivity and all measures of novelty
      exploration were under control of different environmental factors. Interestingly,
      in the dorsal medial prefrontal cortex, a brain region involved in impulsivity
      and activity in novelty exploration tests; these behavioral measures correlated
      with the expression of different genes (respectively, Frzb, Snx5, BC056474 and
      the previously identified Glo1). Taken together, our study shows that impulsivity
      and activity in novelty exploration tests are genetically and environmentally
      distinct, suggesting that mouse models of these behaviors provide complementary
      insights into the development of substance abuse disorder.

PMID- 19751397
TI  - Viral hemorrhagic fevers are often cited by the emerging infections and
      bioterrorism scientific communities. Introduction.

PMID- 19751398
TI  - A mouse model for studying dengue virus pathogenesis and immune response.
AB  - A small animal model for studying dengue disease is of critical importance to
      furthering many areas of dengue research, including host immunity, disease
      pathogenesis, and drug and vaccine development. Recent characterization of the
      AG129 mouse model has demonstrated it to be one of the only models at this time
      that permits infection by all four serotypes of dengue virus (DENV), supports
      replication in relevant cell and tissue types comparable to human infection, and
      allows antibody-mediated protection and enhancement of DENV infection. Thus, this
      model enables testing hypotheses arising from epidemiological observations and in
      vitro experiments in an in vivo system with a functional adaptive immune
      response. This review provides a brief overview of the development of a mouse
      model of DENV infection, describes the work completed to date characterizing the
      AG129 model, and examines several of the unanswered questions remaining in the
      field.

PMID- 19751399
TI  - A re-evaluation of the mechanisms leading to dengue hemorrhagic fever.
AB  - Viremia is one of the features of dengue virus infection among the flaviviruses.
      Dengue virus infection results in a spectrum of clinical symptoms, ranging from
      undifferentiated flu-like illness, mild dengue fever, to dengue hemorrhagic fever
      (DHF)/dengue shock syndrome (DSS), a life-threatening illness. Several mechanisms
      have been hypothesized based primarily on data collected from post-acute clinical
      phase to account for DHF/DSS. Lack of a suitable animal model for DHF/DSS has
      hindered progress in defining the etiology of DHF/DSS. Levels of circulating
      dengue virus have been well-correlated to severe dengue disease. However, the
      cell lineage(s) serving as a primary target for the source of viremia are largely
      unknown. Results from in vivo and in vitro pilot studies using molecular and more
      advanced technologies reveal that dengue virus appears to be associated with
      platelets and the megakaryocytic lineage. The observation may partially explain
      the dysfunction of platelets observed in dengue affected patients.

PMID- 19751400
TI  - T lymphocyte responses to heterologous secondary dengue virus infections.
AB  - The available evidence suggests that plasma leakage in dengue hemorrhagic fever
      is caused by the action of circulating mediators on the vascular endothelium, and
      that the host immune response is a critical determinant of this response. We have
      been exploring the role of dengue virus-specific T lymphocytes in the
      immunopathogenesis of plasma leakage. Memory dengue virus-specific T cells
      induced during a primary dengue virus infection are reactivated by the
      heterologous viral serotype during a secondary infection to expand to high levels
      and produce a skewed cytokine profile. Investigations are underway to identify
      the immunologic profiles associated with increased or decreased risk for severe
      disease.

PMID- 19751401
TI  - Dengue hemorrhage in a mouse model.
AB  - Here we summarized our findings in the mouse model of the events that lead to
      dengue hemorrhage. Immunocompetent mice inoculated intradermally with DENV-2
      strain 16681 develop hemorrhage locally or systemically. The incidence and the
      severity of hemorrhage development are dependent on the size of viral inoculum.
      The hemorrhage mice exhibit severe thrombocytopenia, prolonged bleeding time, and
      increased numbers of circulating endothelial cells. In the hemorrhage tissues,
      there is endothelial damage accompanied by infiltrating macrophages that secret
      TNF-alpha. The endothelial cells express iNOS and peroxynitrite and undergo
      apoptosis, indicating RNS and ROS production may lead to cell death. By using
      mice deficient in iNOS and phox47 and apocynin, we demonstrated that RNS and ROS
      are important to hemorrhage development after infection by DENV. Our mouse model
      offers the opportunity to test potential dengue vaccines and therapeutics to
      treat dengue hemorrhage and to test hemorrhage induction potentials of dengue
      viral strains.

PMID- 19751402
TI  - Antibodies determine virulence in dengue.
AB  - Four dengue viruses (DENV) cause syndromes that are self-limited or severe. The
      severe syndrome, dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS),
      characterized by sudden vascular permeability, is not caused by inherently
      virulent DENV. This syndrome has consistently been observed to accompany dengue
      infections in individuals circulating heterotypic dengue antibodies at enhancing
      concentrations. In humans, dengue infections target monocytes/macrophages where,
      absent neutralization, heterotypic antibodies, perhaps directed at domain I-II of
      the envelope protein form immune complexes, attach to Fc receptors, suppress
      innate immunity, and increase productive infection. Diverse clinical responses to
      primary infections with different DENV strains do occur and occasionally result
      in subclinical vascular permeability observed as hypovolemia. The fact that
      American (AM) genotype DENV 2 produce only mild disease during secondary dengue
      infections is best explained by the downregulation of disease by DENV 1
      antibodies directed at a unique antigenic structure expressed on AM DENV 2.

PMID- 19751403
TI  - Molecular and cell biology of the prototypic arenavirus LCMV: implications for
      understanding and combating hemorrhagic fever arenaviruses.
AB  - Arenaviruses merit interest as experimental model systems to study virus-host
      interactions and as clinically important human pathogens. Several arenaviruses,
      chiefly Lassa virus (LASV), cause hemorrhagic fever (HF) in humans. In addition,
      evidence indicates that the worldwide-distributed prototypic arenavirus
      lymphocytic choriomeningitis virus (LCMV) is a neglected human pathogen.
      Moreover, arenaviruses pose a biodefense threat. No licensed arenavirus vaccines
      are available, and current therapy is limited to the use of ribavirin, which is
      only partially effective and associated with significant side effects. The
      development of arenavirus reverse genetics systems has made it possible to
      manipulate the arenavirus genome, which is contributing to significant progress
      in understanding arenavirus molecular and cell biology, as well as arenavirus
      host interactions underlying arenavirus-induced HF disease in humans. This, in
      turn, should facilitate the development of novel both vaccines and antiviral
      drugs to combat the dual threats of naturally occurring and intentionally
      introduced arenavirus infections.

PMID- 19751404
TI  - Diagnostics and discovery in viral hemorrhagic fevers.
AB  - The rate of discovery of new microbes and of new associations of microbes with
      health and disease is accelerating. Many factors contribute to this phenomenon
      including those that favor the true emergence of new pathogens as well as new
      technologies and paradigms that enable their detection and characterization. This
      chapter reviews recent progress in the field of pathogen surveillance and
      discovery with a focus on viral hemorrhagic fevers.

PMID- 19751405
TI  - Molecular determinants of Pichinde virus infection of guinea pigs--a small animal
      model system for arenaviral hemorrhagic fevers.
AB  - Arenaviruses are enveloped single-strand RNA viruses that mostly have natural
      hosts in rodents. Upon infection of humans, several arenaviruses can cause severe
      hemorrhagic fever diseases, including Lassa fever that is endemic in West Africa.
      The virulence mechanism of these deadly arenaviruses can be studied in a safe and
      economical small animal model-guinea pigs infected by a nonpathogenic arenavirus
      Pichinde virus (PICV), a virulent strain of which can cause similar disease
      syndromes in guinea pigs as arenaviral hemorrhagic fevers in humans. We have
      recently developed molecular clones for both the virulent and avirulent strains
      of PICV. Using the available reverse genetics tools, we are characterizing the
      molecular determinants of virulent arenavirus infections in vivo.

PMID- 19751406
TI  - Dual functions of Rift Valley fever virus NSs protein: inhibition of host mRNA
      transcription and post-transcriptional downregulation of protein kinase PKR.
AB  - Rift Valley fever virus (RVFV), which belongs to the genus Phlebovirus, family
      Bunyaviridae, is a negative-stranded RNA virus carrying a single-stranded,
      tripartite RNA genome. RVFV is an important zoonotic pathogen transmitted by
      mosquitoes and causes large outbreaks among ruminants and humans in Africa and
      the Arabian Peninsula. Human patients develop an acute febrile illness, followed
      by a fatal hemorrhagic fever, encephalitis, or ocular diseases. A viral
      nonstructural protein, NSs, is a major viral virulence factor. Past studies
      showed that NSs suppresses the transcription of host mRNAs, including interferon
      beta mRNAs. Here we demonstrated that the NSs protein induced post
      transcriptional downregulation of dsRNA-dependent protein kinase (PKR), to
      prevent phosphorylation of eIF2alpha and promoted viral translation in infected
      cells. These two biological activities of the NSs most probably have a
      synergistic effect in suppressing host innate immune functions and facilitate
      efficient viral replication in infected mammalian hosts.

PMID- 19751407
TI  - Inhibition of TNF-alpha-induced activation of NF-kappaB by hantavirus
      nucleocapsid proteins.
AB  - Hantaviruses cause two human diseases thought to be immune-mediated: hemorrhagic
      fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). We
      recently reported that the nucleocapsid (N) protein of HFRS-causing Hantaan virus
      (HTNV) inhibits tumor necrosis factor-alpha (TNF-alpha) activation of nuclear
      factor-kappaB (NF-kappaB). Here we measured the ability of other hantaviral N
      proteins to similarly interfere with the inflammatory process of TNF-alpha. We
      found that like HTNV N, the N proteins of HFRS-causing Seoul and Dobrava viruses
      inhibited TNF-alpha activation of NF-kappaB and translocation of the NF-kappaB
      p65 subunit, but did not interfere with degradation of inhibitor of NF-kappaB
      (IkappaB). In contrast, the HFRS-causing Puumala virus and the HPS-causing Andes
      and Sin Nombre viruses did not prevent TNF-alpha activation of NF-kappaB or
      nuclear translocation of p65. These studies provide evidence that hantaviruses
      differ in their abilities to interfere with host innate immune responses.

PMID- 19751408
TI  - Integrative physiology. Preface.

PMID- 19751409
TI  - The role of sirtuins in the control of metabolic homeostasis.
AB  - Recently the function of the sirtuin family, named after their homology to the
      Saccharomyces cerevisiae gene silent information regulator 2 (Sir2), has received
      a lot of attention, as their beneficial impact on longevity was linked to their
      effects on metabolic control. All sirtuins require nicotinamide adenine
      dinucleotide (NAD(+)) for their deacetylase or ADP-ribosyl transferase activity,
      linking their function tightly to cellular energy levels. SIRT1, the founding
      member of the sirtuin family, modulates many aspects of glucose and lipid
      homeostasis in almost all key metabolic tissues. Other members including SIRT2,
      SIRT3, and SIRT4 are also implicated in various metabolic processes. Here, we
      review the recent data related to the role of sirtuins in the control of
      metabolic homeostasis and possible underlying molecular mechanisms.

PMID- 19751410
TI  - From sugar to fat: How the transcription factor XBP1 regulates hepatic
      lipogenesis.
AB  - Lipogenesis occurs primarily in the liver, where dietary carbohydrates control
      the expression of key enzymes in glycolytic and lipogenic pathways. We have
      recently discovered that the transcription factor XBP1, best known as a key
      regulator of the unfolded protein response (UPR), is required for de novo fatty
      acid synthesis in the liver, a function unrelated to its role in the UPR.(1) XBP1
      protein expression is induced in the liver by a high carbohydrate diet and
      directly controls the induction of critical genes involved in fatty acid
      synthesis. Specific deletion of XBP1 in adult liver using an inducible approach
      results in profound hypocholesterolemia and hypotriglyceridemia, which could be
      attributed to diminished production of lipids in the liver. Notably, this
      phenotype is not associated with fatty liver (hepatic steatosis) or significant
      compromise in protein secretion. XBP1 joins an already rich field of
      transcriptional regulatory proteins in the control of hepatic lipogenesis. Its
      function in lipogenesis appears to be highly significant as evidenced by the
      phenotype of the genetic mutant strain. A more complete understanding of the
      mechanisms by which XBP1 accelerates de novo fatty acid synthesis in the liver
      while preserving normal hepatic lipid composition is highly relevant to the
      treatment of diseases such as atherosclerosis and metabolic syndrome that are
      associated with dyslipidemia. Since excess fat accumulation in the liver could
      result from increased hepatic fatty acid synthesis, compounds that inhibit XBP1
      activation may also be useful therapeutics for the treatment of human alcoholic
      liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD), increasingly
      common causes of morbidity and mortality in the United States.

PMID- 19751411
TI  - An Osteoblast-dependent mechanism contributes to the leptin regulation of insulin
      secretion.
AB  - Our work focuses on genetic and molecular mechanisms for the reciprocal
      regulation of bone and energy metabolism orchestrated by leptin and osteocalcin.
      In the context of this reciprocal regulation, the finding that leptin inhibits
      insulin secretion by beta cells while osteocalcin favors it is surprising. In
      exploring the molecular bases of this paradox we found that leptin, as is the
      case for most of its functions, uses a neuronal relay to inhibit insulin
      secretion. Cell-specific gene-deletion experiments revealed that a component of
      this neuronal regulation is the sympathetic innervation to osteoblasts. Under the
      control of leptin the sympathetic tone favors expression in osteoblasts of Esp,
      which inhibits the metabolic activity of osteocalcin. We further identify ATF4 as
      a transcription factor that regulates Esp expression and thereby insulin
      secretion and sensitivity. Taken together these data illustrate the tight
      connections between bone remodeling and energy metabolism and add further
      credence to the notion that the osteoblast is a bona fide endocrine cell type.

PMID- 19751412
TI  - Estrogens maintain bone mass by regulating expression of genes controlling
      function and life span in mature osteoclasts.
AB  - Estrogens play a key role in regulation of bone mass and strength by controlling
      activity of bone-forming osteoblasts and bone-resorbing osteoclasts. Cellular
      effects of estrogens are mediated predominantly by the action of estrogen
      receptor alpha (ERalpha). In earlier studies, ablation of the ERalpha gene in
      mice did not result in osteoporotic phenotypes due to systemic endocrine
      disturbance and compensatory effects of elevated levels of testosterone. Despite
      the relatively well-established effects in osteoblasts, little is known about the
      direct action of estrogen in osteoclasts. Development in the last decade of more
      sophisticated genetic manipulation approaches opened new possibilities to explore
      cell-specific roles of nuclear receptors in bone tissue. Recently, we have
      generated osteoclast-specific ERalpha gene knockout mice and shown that in vivo
      estrogens directly regulate the life span of mature osteoclasts by inducing the
      expression of pro-apoptotic Fas ligand (FasL). Inhibitory effects of estrogens on
      osteoclast function were further studied in vitro. We observed sufficiently
      detectable ERalpha expression in osteoclasts differentiating from primary bone
      marrow cells or RAW264 cells, although levels of ERalpha were decreasing during
      progression of the differentiation into mature osteoclasts. Treatment with
      estrogens led to reduction in expression of osteoclast-specific genes controlling
      bone resorption activity. However, estrogens did not affect the size of
      multinucleated osteoclasts or number of nuclei in a mature osteoclast. In
      conclusion, in osteoclasts, estrogens function to inhibit bone resorption
      activity and vitality rather than differentiation.

PMID- 19751413
TI  - Macrophage apoptosis in advanced atherosclerosis.
AB  - Plaque necrosis in advanced atheromata, which triggers acute atherothrombotic
      vascular events, is caused by the apoptosis of lesional macrophages coupled with
      defective phagocytic clearance of the dead cells. The central enabling event in
      macrophage apoptosis relevant to advanced atherosclerosis is the unfolded protein
      response (UPR), an endoplasmic reticulum (ER) stress pathway. The UPR effector
      CHOP (GADD153) amplifies release of ER Ca(2+) stores, which activates a central
      integrator of apoptosis signaling, calcium/calmodulin-dependent protein kinase II
      (CaMKII). CaMKII, in turn, leads to activation of pro-apoptotic STAT1, induction
      of the death receptor Fas, and stimulation of the mitochondria-cytochrome c
      pathway of apoptosis. While these pathways are necessary for apoptosis, apoptosis
      occurs only when the cells are also exposed to one or more additional "hits."
      These hits amplify pro-apoptotic pathways and/or suppress compensatory cell
      survival pathways. A second hit relevant to atherosclerosis is activation of
      pattern recognition receptors (PRRs), such as scavenger and toll-like receptors.
      In vivo relevance is suggested by the fact that advanced human lesions express
      markers of UPR activation that correlate closely with the degree of plaque
      vulnerability and macrophage apoptosis. Moreover, studies with genetically
      altered mice have shown that ER stress and PRR activation are causative for
      advanced lesional macrophage apoptosis and plaque necrosis. In summary, a key
      cellular event in the conversion of benign to vulnerable atherosclerotic plaques
      is ER stress-induced macrophage apoptosis. Further understanding of the
      mechanisms and consequences of this event may lead to novel therapies directed at
      preventing the clinical progression of atheromata.

PMID- 19751414
TI  - Antigenic phenotype and phagocytic capacity of MG-63 osteosarcoma line.
AB  - Human osteoblasts isolated from bone tissue samples have their own specific
      antigen profile but also share expression of antigens that are characteristic of
      other immunocompetent cells. Given that these findings come from studies
      performed in primary cultures of human osteoblasts, it was decided to test
      whether these antigen profiles and functional characteristics are retained in a
      characterized osteoblast cell line (MG-63). We show that some of these
      characteristics are also found in the MG-63 osteosarcoma cell line. We have
      demonstrated, using monoclonal antibodies and cytometry, that these cells
      expressed CD10, CD13, CD44, and CD54 antigens but were negative for CD69 and HLA
      DR antigens. Functionally, 100% of MG-63 cells showed phagocytic capacity with a
      high phagocytic index. This study corroborates that osteoblastic cells have an
      immunological profile.

PMID- 19751415
TI  - Role of neutrophils in arginine-asymmetric dimethylarginine pathway subsequent to
      endotoxemia.
AB  - There is a striking correlation between nitric oxide (NO) production and
      myeloperoxidase (MPO) enzyme activity accession in various tissues after
      endotoxemia. Both arginine-NO and arginine-asymmetric dimethylarginine (ADMA)
      pathways have been recognized to play critical roles during infection and
      inflammation. We investigated whether there is a link between MPO-mediated
      nitrating pathway and arginine-ADMA pathway after endotoxemia in liver. All
      experiments were performed in two groups (control and endotoxemia) of 10 guinea
      pigs. In this study, 6 h after the administration of endotoxin at a dose of 4
      mg/kg, MPO activity and ADMA, L-arginine, and 3-nitrotyrosine (3-NT, a stable
      product of peroxynitrite formation) levels were measured. Measurement of ADMA and
      L-arginine were accomplished by HPLC with fluorescent detector. 3-NT was
      quantified by HPLC with electrochemical detector. MPO activity was determined by
      spectrophotometric method. After administration of endotoxin, ADMA and L-arginine
      levels decreased, but 3-NT levels and MPO activity increased significantly. In
      conclusion, there is an inverse relationship between MPO-mediated tyrosine
      nitration and arginine-ADMA pathway in liver after endotoxemia.

PMID- 19751416
TI  - Changes of bone formation markers osteocalcin and bone-specific alkaline
      phosphatase in postmenopausal women with osteoporosis.
AB  - The relationship between bone formation markers osteocalcin (OC) and bone
      specific alkaline phosphatase (bALP) and age in postmenopausal women was
      investigated. Forty-eight osteoporotic women (median age 62, range 49-76 years)
      were enrolled in the study. There were 17 (35%) patients aged 49-59 years (Group
      A), and 31 (65%) patients aged over 59 years (Group B). Parathyroid hormone,
      calcium, and creatinine serum levels did not differ significantly between groups.
      Compared with Group A, patients in Group B had higher levels of both OC (28.5 +/-
      17.8 versus 46.2 +/- 19.3 ng/mL; P= 0.003) and bALP (57.3 +/- 12.4 versus 66.4 +/
      8.7 U/L; P= 0.005). A significant relationship between age and both OC (R= 0.49,
      P= 0.002) and bALP (R= 0.41, P= 0.009) was found only in Group B, but there was
      no relationship with bone mineral density. In conclusion, in postmenopausal women
      the increase of bone formation markers later in life may be an expression of
      increased bone turnover, which is partially the cause of osteoporosis.

PMID- 19751417
TI  - Bone mineral density, osteocalcin, and bone-specific alkaline phosphatase in
      patients with insulin-dependent diabetes mellitus.
AB  - The aims of this study were to evaluate the prevalence of osteopenia and the
      relationships between osteocalcin (OC), bone alkaline phosphatase (bALP), and
      bone mineral density (BMD) in patients with insulin-dependent diabetes mellitus
      (IDDM). A group of 18 patients (median age 47, range 36-51) with uncomplicated
      IDDM (Group A) were matched by sex, age, and body mass index with 21 healthy
      control volunteers (Group B). All subjects underwent osteodensitometry with
      measurement of BMD at the lumbar spine and femoral neck. Osteopenia was present
      in 11 (61.1%) and 2 (9.5%) of Group A and B patients (P= 0.01), respectively.
      Both OC (28.4 +/- 16.4 versus 41.2 +/- 14.6 ng/mL; P= 0.005) and bALP (51.3 +/-
      11.8 versus 61.7 +/- 10.6 U/L; P= 0.006) serum levels were significantly lower in
      patients with IDDM. BMD did not correlate with either OC or bALP. In conclusion,
      osteopenia is common among patients with IDDM, but the relationship between bone
      formation markers and BMD is still unclear.

PMID- 19751418
TI  - Aortic stiffness and distensibility among hypertensives.
AB  - Hypertension is one among many factors that contribute to aortic stiffness, which
      has repercussions mainly on the heart. To assess aortic stiffness among essential
      hypertensives of South India and its relationship with gender. An analytical
      study was designed to assess aortic stiffness among 60 nonobese, nonalcoholic,
      nonsmoking, and non-caffeine consuming essential hypertensives without any overt
      illness or infection, and compared with 30 healthy age- and sex-matched
      nonhypertensives. They were assessed clinically and also by laboratory means.
      Their left ventricular mass (LV) and left ventricular ejection fraction (LVEF)
      were measured using Transthoracic echocardiogram. Aortic systolic and diastolic
      diameters were measured by using M-mode echocardiography during consecutive beats
      and averaged for each case. Finally, aortic stiffness was calculated. The data
      were analyzed statistically. Hypertensives were divided into Group I, consisting
      of patients with hypertension at least for 5 years, who were not adherent to
      medication, and Group II, consisting of patients with hypertension of duration
      between 6 months and 1 year. There were 20 males and 10 females in each group.
      There was no significant difference between the hypertensive groups and a
      control, normotensive, group with regard to BMI or total cholesterol. The means
      of LV mass (in grams), systolic BP (in mmHg), diastolic BP (in mmHg), aortic
      systolic diameter (in mm), aortic diastolic diameter (in mm), aortic
      distensibility (in mm), and aortic stiffness found in Group I, Group II, and
      controls were 105.8 +/- 23.8, 101.5 +/- 21, and 84 +/- 9.8; 138 +/- 14.2, 153 +/-
      17.1, and 120 +/- 8.3; 90.5 +/- 11.6, 101.7 +/- 17.1, and 76.5 +/- 5; 30.85 +/-
      2.6, 28.7 +/- 2.6, and 27.7 +/- 2.4; 28.7 +/- 2.2, 25.8 +/- 2.5, and 24.2 +/-
      2.5; 2.14 +/- 0.3, 2.84 +/- 0.5, and 3.5 +/- 0.6; and 1.31 +/- 0.09, 1.14 +/-
      0.1, and 1.04 +/- 0.08, respectively. The differences between the hypertensive
      groups and the control group were significant. Aortic stiffness was greater in
      hypertensives and it was independent of gender, but increased with duration of
      hypertension. Hypertension has effects on the aorta (decreased aortic
      distensibility and increased aortic stiffness) and left ventricle (increased left
      ventricular mass and left ventricular hypertrophy). These changes can be
      identified and monitored while the patient is on antihypertensive therapy along
      with life-style modifications, as these are reversible. Nevertheless, these
      aspects do not receive due attention in medical education and training on
      hypertension.

PMID- 19751419
TI  - Antibiotic resistance in bacteria: novel metalloenzyme inhibitors.
AB  - Beta-lactam antibiotics are among the most important drugs used to fight
      bacterial infection. Overuse and misuse of beta-lactam antibiotics has caused the
      evolution of resistance mechanisms, allowing pathogenic bacteria to survive
      antibiotic treatment. The major source of resistance to beta-lactam antibiotics
      occurs through production of enzymes called beta-lactamases capable of catalyzing
      hydrolysis of the beta-lactam rings in these drug compounds. The metallo-beta
      lactamases have become a major threat due to their broad substrate specificities;
      there are no clinically useful inhibitors for these metalloenzymes. We have
      obtained single-stranded DNA's that are potent inhibitors of the Bacillus cereus
      5/B/6 metallo-beta-lactamase. These are rapid, reversible, non-competitive
      inhibitors of the metalloenzyme, with K(i) and K(i)' values in the nanomolar
      range. The inhibition patterns and metal ion dependence of their inhibition
      suggest that the oligonucleotides alter the coordination of the active site metal
      ion(s); inhibition is efficient and highly specific. Microbiological growth
      experiments, using combinations of ssDNA with the beta-lactam antibiotic
      cephalexin, reveal that the inhibitor is capable of causing cell death in liquid
      cultures of both Gram-positive and Gram-negative metallo-beta-lactamase producing
      bacteria in the micromolar concentration range.

PMID- 19751420
TI  - Quantitative structure-activity relationship models for predicting biological
      properties, developed by combining structure- and ligand-based approaches: an
      application to the human ether-a-go-go-related gene potassium channel inhibition.
AB  - A strategy for developing accurate quantitative structure-activity relationship
      models enabling predictions of biological properties, when suitable knowledge
      concerning both ligands and biological target is available, was tested on a data
      set where molecules are characterized by high structural diversity. Such a
      strategy was applied to human ether-a-go-go-related gene K(+) channel inhibition
      and consists of a combination of ligand- and structure-based approaches, which
      can be carried out whenever the three-dimensional structure of the target
      macromolecule is known or may be modeled with good accuracy. Molecular
      conformations of ligands were obtained by means of molecular docking, performed
      in a previously built theoretical model of the channel pore, so that descriptors
      depending upon the three-dimensional molecular structure were properly computed.
      A modification of the directed sphere-exclusion algorithm was developed and
      exploited to properly splitting the whole dataset into Training/Test set pairs.
      Molecular descriptors, computed by means of the codessa program, were used for
      the search of reliable quantitative structure-activity relationship models that
      were subsequently identified through a rigorous validation analysis. Finally,
      pIC(50) values of a prediction set, external to the initial dataset, were
      predicted and the results confirmed the high predictive power of the model within
      a quite wide chemical space.

PMID- 19751421
TI  - Survival among patients with left ventricular systolic dysfunction treated with
      atenolol.
AB  - Metoprolol succinate, carvedilol, and bisoprolol are approved for use in heart
      failure. Other beta-blockers have been found to be inferior (metoprolol tartrate)
      or have not been studied (atenolol). The authors compared all-cause mortality
      following treatment with either atenolol, carvedilol, or metoprolol tartrate for
      974 patients with left ventricular function < or =40%. The unadjusted mortality
      at 6 months was lower with atenolol (3.2%) and carvedilol (4.2%) when compared
      with metoprolol tartrate (7.5%, P< or =.039). However, patients with atenolol
      were older but had less prior heart failure. After adjustment for the propensity
      to be treated with atenolol, patients actually treated with atenolol had a
      significantly lower risk of death compared with treatment with metoprolol
      tartrate and comparable outcome to those treated with carvedilol. These results
      suggest that atenolol may be useful for patients with heart failure treatment and
      highlight the need for a randomized trial comparing atenolol with established
      beta-blockers.

PMID- 19751422
TI  - Identifying left ventricular dysfunction in pulmonary hypertension.
AB  - The significance of left ventricular (LV) dysfunction in patients with pulmonary
      hypertension (PH) is unknown. Our purpose was to quantify LV function in PH
      patients by measuring LV myocardial performance index (MPI) and correlating it
      with invasively determined hemodynamic variables. The authors prospectively
      measured LV MPI via transthoracic echocardiography in 50 patients with PH (53+/
      11 years; 35 women) who also underwent right heart catheterization within 1 day
      of echocardiography. For comparative purposes, LV MPI was also measured in 15
      healthy volunteers who served as controls. LV MPI was significantly increased in
      the PH group compared with controls (0.62+/-0.27 vs 0.36+/-0.08; P<.001),
      indicating worse LV dysfunction despite that LV ejection fraction was not
      significantly different between the groups (58%+/-4% vs 60%+/-3%). LV MPI
      demonstrated significant correlations with invasively determined mean pulmonary
      artery pressure (r=.50; P<.001), pulmonary vascular resistance (r=.57; P<.001),
      and cardiac index (r=-.64; P<.001). By receiver operating characteristic
      analysis, LV MPI >0.75 predicted cardiac index <2 L/min/m(2) with 89% sensitivity
      and 78% specificity (area under the curve, 0.89). In a multivariate model, LV MPI
      was independently associated with cardiac index (P<.01). Patients with PH
      demonstrate abnormal LV function as quantified by elevated LV MPI, which
      correlates significantly with pulmonary vascular resistance and cardiac index.

PMID- 19751423
TI  - Pulse pressure and QRS width evaluation as an inexpensive tool for heart failure
      assessment.
AB  - Decreased pulse pressure (PP) is associated with low cardiac output and increased
      mortality in heart failure (HF) inpatients. QRS width is a well-known prognostic
      factor in HF. The study purpose was to explore the mortality effect of combining
      PP and QRS width in HF outpatients. Initial sphygmomanometrically determined PP
      and QRS width on the first electrocardiograph in 327 consecutive patients at an
      HF clinic were recorded. According to PP > or = or <40 mm Hg and QRS width > or =
      or <120 ms, patients were classified into 4 groups. Study groups were analyzed
      for their effect on mortality using Cox proportional hazards regression analysis.
      Patients with PP <40 mm Hg had higher mortality (59% vs 45%; P=.015). QRS width >
      or =120 ms indicated a trend toward higher mortality (57% vs 48%; P=.067).
      Actuarial survival curves showed that group 4 (QRS width > or =120 ms and PP <40
      mm Hg) had significant increased mortality risk in 3.5 years' mean follow-up.
      Group 4 had a mean survival time of 1124 days (SD=124) vs 2233 days (SD=285) in
      group 1 (QRS width <120 ms and PP > or =40 mm Hg) (P=.022). There was a linear
      association between left ventricular ejection fraction (LVEF) and study groups.
      PP and QRS width are readily available, inexpensive, and relevant clinical
      measures to help identify HF outpatients with significantly worse prognosis and
      decreased LVEF.

PMID- 19751424
TI  - Sleep and health-related quality of life in heart failure.
AB  - This study characterized sleep in heart failure (HF) and determined associations
      with quality of life. Forty stable HF patients and 34 healthy volunteers were
      studied in a clinical research unit. HF patients had more central apneas per hour
      (17.6 vs 5.4; P< or =.01) and obstructive apneas per hour (21.7 vs 8.5; P< or
      =.05), spent more time in stage 1 sleep (54 vs 35 min; P< or =.05), and had more
      respiratory awakenings following apneic events (27.2 vs 4.2; P< or =.01). More HF
      patients were depressed (55% vs 27.2%; P< or =.01) and had worse fatigue (P< or
      =.05). In multiple regression analysis, physical functioning quality of life was
      predicted by reduced left ventricular ejection fraction (P< or =.05), shorter
      distance on a 6-minute walk test (P< or =.05), greater fatigue (P< or =.01), and
      more apneas ( P< or =.05) (model R(2)=.672; P< or =.001). Emotional functioning
      quality of life was predicted by greater fatigue (P< or =.01) (model adjusted
      R(2)=.732; P<.001). Findings provide evidence that in addition to functional
      status and ongoing fatigue, poorer quality of life in HF is independently related
      to the severity of sleep-disordered breathing.

PMID- 19751425
TI  - Prognostic utility of right ventricular systolic functions assessed by tissue
      doppler imaging in dilated cardiomyopathy and its correlation with plasma NT-pro
      BNP levels.
AB  - The authors invesitgated the impact of right ventricular systolic function
      measured by tissue Doppler imaging on clinical end points and its correlation
      with plasma NT-pro-BNP levels in 75 patients with nonischemic dilated
      cardiomyopathy. Echocardiographic peak systolic velocities of tricuspid lateral
      annulus by tissue Doppler imaging and plasma pro-B-type natriuretic peptide (NT
      pro-BNP) levels were measured. Forty patients had clinical end points in 29+/-16
      months. They were found to have higher plasma NT-pro-BNP levels and lower
      tricuspid lateral annulus and interventricular septum tissue Doppler peak
      systolic velocities than patients without clinical end points. Cut-off level of
      plasma NT-pro-BNP levels for predicting clinical end points was 1700 pg/mL
      (sensitivity and specificity, 82% and 75%, respectively). Cut-off level of
      tricuspid lateral annulus tissue Doppler peak systolic velocities for predicting
      clinical end points was 6.25 cm/sec (sensitivity and specificity, 80% and 57%,
      respectively). In conclusion, plasma NT-pro-BNP levels and tissue Doppler-derived
      right ventricular systolic functional parameters are helpful in determining
      prognosis in dilated cardiomyopathy.

PMID- 19751426
TI  - How does volume status affect BNP and troponin levels as markers of
      cardiovascular status in peritoneal dialysis?
AB  - Cardiac biomarkers such as brain natriuretic peptide, amino-terminal pro-B-type
      natriuretic peptide (NT-proBNP), and cardiac troponin provide information on
      cardiovascular morbidity and mortality in patients with normal renal function. In
      a considerable number of chronic hemodialysis patients, both biomarkers-NT-proBNP
      and troponin-are elevated despite the absence of cardiac ischemia. The elevation
      of cardiac biomarkers in chronic hemodialysis patients is of prognostic value
      with respect to cardiovascular morbidity and mortality. Furthermore, they can
      serve as tools for volume assessment for optimization of the fluid management
      aspect of dialysis. However, the association of both these markers in peritoneal
      dialysis is not clear. Therefore, the authors reviewed the literature to examine
      the role of these markers in peritoneal dialysis patients both as prognostic
      indicators as well as tools for volume assessment.

PMID- 19751427
TI  - Regression of normalized left ventricular systolic function after discontinuation
      of treatment in patients with dilated cardiomyopathy.

PMID- 19751428
TI  - Coronary artery embolus complicating dilated cardiomyopathy.

PMID- 19751429
TI  - Electrical instability heralding worsening heart failure in a patient with
      nonischemic dilated cardiomyopathy.

PMID- 19751430
TI  - Cardiogenic unilateral pulmonary edema: an unreported complication of a digestive
      endoscopic procedure.
AB  - Unilateral pulmonary edema is an uncommon clinical situation that may be
      difficult to distinguish from other conditions that cause lung infiltrates. Most
      cases occur in the right lung, and there are no reports about cardiogenic
      unilateral pulmonary edema as a complication of an endoscopic procedure of
      gastrointestinal tract. The authors describe a case of a 79-year-old woman with
      acute cardiac heart failure that developed soon after a diagnostic upper and
      lower digestive endoscopy. Continuous positive airway pressure, intravenous
      nitroglycerin, and furosemide treatment resulted in rapid improvement of symptoms
      and the progressive resolution of left-sided infiltrates on chest radiography.
      This case is of particular importance because of the rarity of cardiogenic
      unilateral edema in the left lung. This clinical finding was associated with the
      prolonged rest on the left side during the gastrointestinal endoscopic procedure.

PMID- 19751431
TI  - Moxifloxacin-containing triple therapy as second-line treatment for Helicobacter
      pylori infection: effect of treatment duration and antibiotic resistance on the
      eradication rate.
AB  - BACKGROUND AND AIM: The aim of this study was to evaluate the efficacy of a
      moxifloxacin-containing triple therapy as second-line treatment for Helicobacter
      pylori infection. We also investigated the effect of treatment duration and
      antibiotic resistance on the eradication rate of this therapy. METHODS: We
      prospectively enrolled patients found to have persistent H. pylori infections
      after failure of first-line proton-pump inhibitor-based triple therapy. Patients
      took moxifloxacin (400 mg q.d.), amoxicillin (1000 mg b.i.d.), and esomeprazole
      (20 mg b.i.d.). The eradication rate, drug compliance, and adverse event rates
      were evaluated. Minimal inhibitory tests were performed for moxifloxacin and
      amoxicillin by the agar dilution method. RESULTS: In 2004, 41 patients were
      treated for 7 days. The intention-to-treat and per-protocol eradication rates
      (ITT/PP) were 75.6/83.8%. Moxifloxacin resistance was 5.6%. Therapy was extended
      to 10 days during 2005-2006 and 139 patients were treated. The ITT/PP eradication
      rates were 71.9/82.6%; moxifloxacin resistance had increased to 12%. The final
      group of 181 patients in 2007-2008 who were treated for 14 days also had low
      eradication rates (68/79.9%), but there was no statistical significance in the
      efficacy among the treatment periods. Moxifloxacin resistance in 2007-2008 was
      28.2%. Side-effect increased with treatment duration (i.e., 9.8, 12.2, and 25.4%
      at 7, 10, and 14 days, respectively, p = .001). CONCLUSION: The 7-day
      moxifloxacin-containing triple therapy produced an unacceptably low eradication
      rate. Increasing the duration of therapy was expected to increase the eradication
      rate, but the expected increased did not materialize, most likely because of
      coincident marked increase in the prevalence of resistance to moxifloxacin.
      Tailored treatment based on antibiotic susceptibility testing might be more
      effective in the achievement of high eradication rate when rapid antibiotic
      resistance such as moxifloxacin is occurring.

PMID- 19751432
TI  - Annual change of primary resistance to clarithromycin among Helicobacter pylori
      isolates from 1996 through 2008 in Japan.
AB  - BACKGROUND: Recent studies have shown that the combination of proton pump
      inhibitor, amoxicillin and clarithromycin is one of the best choices for
      Helicobacter pylori eradication therapy. However, increasing number of cases of
      H. pylori infection showing resistance to clarithromycin therapy has been
      reported and this is currently the main cause of eradication failure. We
      investigated the annual changes of the antimicrobial susceptibility to
      clarithromycin, amoxicillin and minocycline during a period of 12 years in Japan.
      METHODS: This study comprised 3521 patients (mean age (SD), 55.4 (13.7) years
      old, 2467 males and 1054 females) positive for H. pylori as assessed by
      microaerobic bacterial culture from 1996 through 2008. All patients were
      previously untreated for H. pylori and were enrolled in the study to assess
      primary resistance to the three antibiotics. RESULTS: The overall primary
      resistance to clarithromycin, amoxicillin and minocycline were 16.4%, (577/3521),
      0.03% (1/3521) and 0.06% (2/3521), respectively. From 1996 through 2004, the
      resistance rate to clarithromycin increased gradually to approximately 30% and
      then it remained without marked fluctuation since 2004. Analysis by gender showed
      a significant increase (p < .0001) in resistance rate to clarithromycin among
      females (217/1057, 20.6%) compared to males (360/2467, 14.6%). Analysis by age,
      disclosed significantly (p < .0001) higher resistance rate to clarithromycin in
      patients of more than 65-years-old compared to the younger population.
      CONCLUSIONS: The resistance rate of H. pylori infection to clarithromycin in
      Japan has increased gradually to approximately 30% from 1996 through 2004, and
      remained unchanged since 2004. Elderly and females were at high risk of having
      resistance to clarithromycin. Our results suggested that the level of
      clarithromycin resistance in Japan has now risen to the point where it should no
      longer be used as empiric therapy.

PMID- 19751433
TI  - Variables influencing outcome of Helicobacter pylori eradication therapy in South
      China.
AB  - BACKGROUND: Therapy combining a proton pump inhibitor (PPI), clarithromycin and
      either amoxicillin or metronidazole is widely recommended for first-line
      treatment for Helicobacter pylori infection. The purpose of this study was to
      examine the outcomes of PPI-containing triple therapy and identify factors
      influencing the cure rate of H. pylori infection in South China. MATERIALS AND
      METHODS: H. pylori positive patients with different occupations from 25 hospitals
      in five provinces of South China were enrolled. They received a PPI,
      metronidazole and amoxicillin triple therapy for a week. H. pylori eradication
      was evaluated by (13)C-urea breath test 4 weeks after therapy. Association
      between H. pylori eradication with occupation, gender, age, educational level,
      and protocol compliance was evaluated by Logistic regression. RESULTS: Six
      hundred and seventy-five were enrolled. The intention-to-treat and per-protocol
      analyses showed overall cure rates of 60% (95% CI = 56.3-63.7%) and 64.5% (95% CI
      = 60.7-68.3%), respectively. Multivariate logistic regression showed that
      occupation, gender and protocol compliance were positively associated with the
      eradication rate (p < .01). The cure rate for those who took 80% or more of the
      prescribed drugs was 64.5% (95% CI = 60.7-68.3%) versus 14.6% (95% CI = 6-29%, p
      < .001) for those who took less. Lower eradication rates were also observed in
      farmers and women. CONCLUSIONS: The eradication rate with a PPI, metronidazole
      and amoxicillin triple therapy was unacceptably low in South China. These results
      suggest that studies of the eradication of H. pylori infection in China must take
      into account antibiotic resistance as well as patient occupation, gender, and
      protocol compliance. Gastric cancer and peptic ulcer disease are both important
      in China making methods to effectively and efficiently eradicate H. pylori a
      priority.

PMID- 19751434
TI  - Meta-analysis: Lactobacillus containing quadruple therapy versus standard triple
      first-line therapy for Helicobacter pylori eradication.
AB  - BACKGROUND: Recent evidence showed that Lactobacilli could exert an inhibitory
      effect on Helicobacter pylori both in vitro and in vivo models. To systematically
      evaluate whether adding Lactobacilli to H. pylori eradication regimens could
      improve eradication rates and reduce side effects during anti-H. pylori
      treatment. MATERIALS AND METHODS: Eligible articles were identified by searches
      of electronic databases. We included all randomized trials comparing Lactobacilli
      supplementation to placebo or no treatment during anti-H. pylori regimens.
      Statistical analysis was performed with Review Manager 5.0.10. Subanalysis
      analysis was also performed. RESULTS: We identified eight randomized trials (n =
      1372). Pooled H. pylori eradication rates were 82.26% (95% CI = 78.01-86.51%) and
      76.97% (95% CI = 73.11-80.83%) for patients with or without Lactobacilli by
      intention-to-treat analysis, respectively, the odds ratio (OR) was 1.78 (95% CI =
      1.21-2.62). The occurrence of total side effects had no significant difference
      and were 30.84% (95% CI = 24.82-36.86%) and 42.24% (95% CI = 35.89%-48.59%) for
      two groups, the summary OR was 0.49 (95% CI = 0.24-1.02); However, Lactobacilli
      supplementation group had lower occurrence of diarrhoea, bloating and taste
      disturbance. CONCLUSIONS: Our review suggests that supplementation with
      Lactobacilli could be effective in increasing eradication rates of anti-H. pylori
      therapy for first-treated patients. Furthermore, Lactobacilli showed a positive
      impact on some H. pylori therapy-related side effects.

PMID- 19751435
TI  - A population-based epidemiologic study of Helicobacter pylori infection and its
      association with systemic inflammation.
AB  - BACKGROUND: Infection with Helicobacter pylori is associated with a variety of
      non-gastrointestinal sequelae. These may be mediated by an increase in systemic
      inflammation. We assessed if serologic evidence of infection with H. pylori is
      associated with increased serum C-reactive protein (CRP) levels. METHODS: The
      study design consisted of a randomly selected, cross-sectional population-based
      study of 2633 individuals phenotyped in 1991, of whom 2361 participants provided
      serum samples to permit measurement of H. pylori's serologic status and CRP
      levels. RESULTS: Male gender (odds ratio (OR): 1.65; 95% confidence interval
      (CI): 1.23-2.21), age (OR per year: 1.05; 95% CI: 1.04-1.06), height (OR per
      meter: 0.05; 95% CI: 0.01-0.24), current smoking habit (compared with never
      smokers, OR: 1.46; 95% CI: 1.13-1.88), and less affluent socioeconomic status
      were associated with increased odds of being seropositive for H. pylori.
      Helicobacter pylori infection was associated with increased risk of having an
      elevated serum CRP (above 3 mg/L) after adjustment for gender, age, height,
      smoking status, and socioeconomic status (OR: 1.32; 95% CI: 1.05-1.67). Similar
      associations were seen using a threshold for elevated serum CRP of greater than 1
      mg/L. CONCLUSIONS: Our data suggest that infection with H. pylori is associated
      with increased systemic inflammation. This suggests one potential mechanism to
      explain the extra-gastrointestinal conditions associated with H. pylori
      infection.

PMID- 19751436
TI  - Interaction of Helicobacter pylori with genetic variants in the MDM2 promoter, is
      associated with gastric cancer susceptibility in Chinese patients.
AB  - BACKGROUND AND AIMS: MDM2 is a major negative regulator of p53, and a single
      nucleotide polymorphism (SNP) in the MDM2 promoter region SNP309 (rs2279744) has
      been shown to increase the affinity of the transcriptional activator Sp1,
      resulting in elevated MDM2 transcription and expression in some cancers. The aim
      of this study was to determine whether SNP309 is associated with susceptibility
      to gastric cancer in Chinese patients. METHODS: Two hundred and sixty patients
      with gastric cancer and 260 healthy controls were genotyped for MDM2 SNP309 using
      the PCR-RFLP method. Helicobacter pylori's infection status was determined using
      a validated serology test. RESULTS: The healthy control group was found to be in
      Hard-Weinberg equilibrium at the polymorphic loci studied (chi(2) = 3.63, p =
      0.06). Multiple logistic regression analyses revealed that the risk of gastric
      cancer for SNP309 (G/G) was significantly increased when compared with T carriers
      (adjusted odds ratio (OR): 2.05, 95% confidence interval (CI): 1.31-3.20).
      Further stratification analyses based on the recessive models reveal that a
      significantly increased risk of gastric cancer associated with the GG genotype
      was evident among subjects with H. pylori infection (adjusted OR: 2.52, 95% CI:
      1.45-4.37), and noncardia gastric cancer patients (adjusted OR: 2.29, 95% CI:
      1.41-3.71), compared with the T carriers. When stratified by histologic subtype
      of gastric cancer, the risk was also statistically significant. There was no
      significant difference in age at diagnosis among genotypes. CONCLUSIONS: The MDM2
      promoter SNP309 is associated with the presence of gastric cancer in Chinese
      patients especially those with H. pylori infection.

PMID- 19751437
TI  - Genetic variation in a4GnT in relation to Helicobacter pylori serology and
      gastric cancer risk.
AB  - BACKGROUND: Helicobacter pylori, a known risk factor of gastric cancer, rarely
      colonize the deeper portion of normal gastric glands, where the mucus is rich in
      alpha-1,4-linked N-acetylglucosamine capped O-glycans, that strongly inhibit H.
      pylori growth in vitro. MATERIALS AND METHODS: We investigated the association
      between genetic variation in the O-glycan transferase encoding gene (a4GnT) and
      H. pylori infection and gastric cancer risk using a Polish population-based case
      control study (273 gastric cancer patients and 377 controls). RESULTS: A
      haplotype at the rs2622694-rs397266 locus was associated with H. pylori
      infection, with the A-A haplotype associated with a higher risk compared with the
      most frequent G-G haplotype (odds ratio 2.30; 95% confidence interval 1.35-3.92).
      The association remained significant after correction for multiple tests (global
      p value: nominal 0.002, empirical 0.045). Neither this haplotype nor the tagSNPs
      were associated with overall gastric cancer risk. CONCLUSION: a4GnT genetic
      variation may be relevant to H. pylori infection, but not to gastric cancer risk.

PMID- 19751438
TI  - Helicobacter pylori infection and family history of gastric cancer decrease
      expression of FHIT tumor suppressor gene in gastric mucosa of dyspeptic patients.
AB  - BACKGROUND: The expression of a fragile histidine triad (FHIT) protein is lost in
      stomach tumors. The study aimed at determining whether FHIT expression is
      affected by Helicobacter pylori infection, strain virulence (vacA and cagA genes)
      and histopathological changes in the gastric mucosa of patients with functional
      dyspepsia having first-degree relatives with gastric cancer. MATERIALS AND
      METHODS: Eighty-eight never-smoking patients with functional dyspepsia were
      selected for the study, and 48 of them had first-degree relatives with gastric
      cancer. Bacterial DNA amplification was used to identify H. pylori colonization.
      The level of FHIT gene expression was determined by qRT-PCR (mRNA) and Western
      blot (FHIT protein) analyses. RESULTS: For patients having first-degree relatives
      with gastric cancer FHIT expression was lower (mRNA by ca. 40-45% and protein by
      30%) compared with the control patients (p < .05). H. pylori infection decreased
      the FHIT mRNA level by 10-35% and the protein level by 10-20%. Bacterial strain
      vacA(+)cagA(+) lowered FHIT mRNA by ca. 30-35% in the antrum samples of both
      groups and in corpus samples of patients with first-degree relatives with gastric
      cancer (p < .05). The FHIT mRNA level was twice as high in control H. pylori
      negative patients with intestinal metaplasia, compared with those with non
      atrophic gastritis. CONCLUSIONS: The decreased FHIT gene expression associated
      with hereditary factors and with H. pylori infection, especially with
      vacA(+)cagA(+)-positive strains, may be related to gastric carcinoma development.

PMID- 19751439
TI  - Evaluation of a new tumor necrosis factor-alpha-inducing membrane protein of
      Helicobacter pylori as a prophylactic vaccine antigen.
AB  - BACKGROUND: Tumor necrosis factor (TNF)-alpha-inducing protein (Tip alpha) is a
      newly identified carcinogenic factor present in Helicobacter pylori. Tip alpha
      has the unique function of inducing TNF-alpha production by gastric cells in
      vitro and is assumed to be related with the development of gastritis and gastric
      cancer. We investigated the effects of vaccination with Tip alpha against H.
      pylori infection and analyzed the immune responses. METHODS: C57BL/6 mice were
      immunized via the intranasal route with CpG, recombinant Tip alpha + CpG, and
      recombinant del-Tip alpha (a mutant of Tip alpha) + CpG. Eight weeks after the
      mice were infected with H. pylori (5 x 10(7) CFU), the number of colonizing
      bacteria in the stomach was calculated, and the histological severity of
      gastritis was evaluated. Levels of Tip alpha-specific IgG and IgA antibodies in
      mouse serum were measured by an enzyme-linked immunosorbent assay (ELISA). Local
      production of cytokines including Interleukin (IL)-10, TNF-alpha and Interferon
      (IFN)-gamma in gastric mucosa was also measured by real time-PCR. RESULTS: Levels
      of Tip alpha-specific antibodies were significantly higher in Tip alpha-immunized
      and del-Tip alpha-immunized mice than in the infection control group. The numbers
      of colonizing bacteria were significantly reduced in Tip alpha-immunized mice
      (4.29 x 10(5) CFU/g) and del-Tip alpha immunized mice (2.5 x 10(5 )CFU/g)
      compared with infection control mice (5.7 x 10(6) CFU/g). The levels of IFN-gamma
      and IL-10 were significantly higher in del-Tip alpha-immunized mice than the
      infection control group. CONCLUSION: Vaccinations with Tip alpha and del-Tip
      alpha were effective against H. pylori infection. The inhibition of H. pylori
      colonization is associated mainly with Th1 cell-mediated immunity.

PMID- 19751440
TI  - Helicobacter pylori infection significantly increases insulin resistance in the
      asymptomatic Japanese population.
AB  - BACKGROUND: Helicobacter pylori infection has been shown to contribute to
      atherosclerosis and cardiovascular diseases. Insulin resistance is the
      pathophysiologic background of the clinical features of atherosclerosis and
      cardiovascular diseases. We examined the association between H. pylori infection
      and insulin resistance in a large Japanese population. MATERIALS AND METHODS:
      Fifteen hundred ninety-eight consecutive asymptomatic subjects that underwent a
      complete medical survey in our institute between May 2007 and July 2008 were
      recruited. Cases under medication for hypertension, hyperlipidemia, diabetes
      mellitus, hyperuricemia, or cardiovascular diseases were excluded from the study.
      Cases suffering from chronic renal or liver failure were also excluded. The
      homeostasis model assessment of insulin resistance (HOMA-IR) score was used to
      quantitatively estimate insulin resistance. Visceral and subcutaneous adipose
      tissues (SAT) were measured by computed tomography. The association between H.
      pylori serostatus and HOMA-IR score was investigated by multivariate regression
      analysis. RESULTS: A total of 988 men and 119 women were eventually eligible for
      this cross-sectional survey. Helicobacter pylori seropositivity was significantly
      higher in 99 cases with insulin resistance (HOMA-IR >or=2.5) compared with 1008
      cases without insulin resistance (HOMA-IR <2.5) (39.4 vs 28.7%, p = .027). There
      was a significant association between H. pylori serostatus and HOMA-IR score by
      multiple linear regression analysis (coefficients = 0.152, 95% CI = 0.058-0.246,
      p = .001), after adjusting for sex, age, body mass index, waist girth, visceral
      and subcutaneous adipose tissues, smoking status, alcohol consumption, dietary
      habits, and physical activity. CONCLUSIONS: Helicobacter pylori infection
      significantly and independently contributed to promoting insulin resistance in a
      large asymptomatic population.

PMID- 19751442
TI  - Better understanding of cholesterol from the egg.

PMID- 19751443
TI  - Dietary cholesterol and the risk of cardiovascular disease in patients: a review
      of the Harvard Egg Study and other data.
AB  - For many years, both the medical community and the general public have
      incorrectly associated eggs with high serum cholesterol and being deleterious to
      health, even though cholesterol is an essential component of cells and organisms.
      It is now acknowledged that the original studies purporting to show a linear
      relation between cholesterol intake and coronary heart disease (CHD) may have
      contained fundamental study design flaws, including conflated cholesterol and
      saturated fat consumption rates and inaccurately assessed actual dietary intake
      of fats by study subjects. Newer and more accurate trials, such as that conducted
      by Frank B. Hu of the Harvard School of Public Health (1999), have shown that
      consumption of up to seven eggs per week is harmonious with a healthful diet,
      except in male patients with diabetes for whom an association in higher egg
      intake and CHD was shown. The degree to which serum cholesterol is increased by
      dietary cholesterol depends upon whether the individual's cholesterol synthesis
      is stimulated or down-regulated by such increased intake, and the extent to which
      each of these phenomena occurs varies from person to person. Several recent
      studies have shed additional light on the specific interplay between dietary
      cholesterol and cardiovascular health risk. It is evident that the dynamics of
      cholesterol homeostasis, and of development of CHD, are extremely complex and
      multifactorial. In summary, the earlier purported adverse relationship between
      dietary cholesterol and heart disease risk was likely largely over-exaggerated.

PMID- 19751444
TI  - The good and the bad: what researchers have learned about dietary cholesterol,
      lipid management and cardiovascular disease risk since the Harvard Egg Study.
AB  - BACKGROUND: The prevalence of cardiovascular diseases, while lower than it once
      was, remains a significant health consideration. AIMS AND METHODS: To review the
      evolving evidence with respect to what role various factors play in the aetiology
      of coronary heart disease (CHD). RESULTS: While total cholesterol and low-density
      lipoprotein cholesterol (LDL-C) were previously believed to play central roles,
      it has now become clear that neither in isolation is highly significant. For
      example, some people with very high LDL-C levels do not develop CHD, while others
      with very low LDL-C levels do. Furthermore, there is a difference between dietary
      cholesterol and serum cholesterol. Dietary cholesterol, which is found in animal
      based foods, raises blood cholesterol in only approximately one-third of people.
      Conversely, intake of saturated fatty acids and trans fatty acids can result in
      dyslipidaemia. Furthermore, obesity--particularly abdominal obesity--and
      metabolic syndrome both are strong independent risk factors for development of
      cardiovascular disease. CONCLUSIONS: Statin therapy and a diet comprising a
      portfolio of plant sterols and viscous fibres can both significantly reduce LDL-C
      levels and C-reactive protein. The latter is a key marker of inflammation and of
      elevated risk for cardiovascular disease.

PMID- 19751445
TI  - Dietary cholesterol and other nutritional considerations in people with diabetes.
AB  - BACKGROUND: Nutrition therapy is an integral component of lifestyle intervention
      and self-management of people with diabetes. The goals of nutrition therapy are
      to optimise or maintain quality of life, physiological and mental health, and to
      prevent and treat acute and long-term complications of diabetes, the associated
      comorbid conditions and concomitant disorders. Monitoring dietary cholesterol
      consumption and salt intake are important nutritional aspects to lower the risk
      for and treatment of cardiovascular disease and hypertension. AIMS: To evaluate
      the role of nutritional therapy and notably the effect of egg consumption on
      cardiovascular disease (CVD) risk in people with diabetes. METHODOLOGY:
      Literature review of nutritional therapy and clinical studies on egg consumption
      and CVD risk for people with diabetes were conducted and appraised. RESULTS: The
      Harvard Egg Study on two large prospective US cohorts found that eating one or
      more eggs a day had no adverse effects on lipid profile or cardiovascular disease
      risk in men or women. Similar findings were observed in the NHANES-I and
      Physicians' Health Study. The only exception was people with diabetes, where CVD
      was increased with eating more than one egg per day. CONCLUSIONS: Consumption of
      one or more eggs per day is associated with an elevated risk of coronary heart
      disease in people with diabetes. The mechanism for this association remains
      unknown but should be explored in randomised clinical trials.

PMID- 19751446
TI  - Talking with your patients about dietary cholesterol, diet and nutrition: best
      practices for family physicians.
AB  - BACKGROUND: Family physicians, as gatekeepers for the healthcare system, are at
      the forefront of detecting, diagnosing, and managing diseases. When it comes to
      coronary heart disease (CHD), patients expect them to be knowledgeable about ways
      to reduce CHD risk, such as through diet. Unfortunately, most family physicians
      have not received formal training about nutritional counselling for patients.
      There is also little time or incentive to educate patients about diet. RESULTS:
      This has led to the preference for referring patients for dietary counselling.
      However, when properly informed, family physicians can be effective conduits for
      dietary counselling. A Danish study showed that patients at risk for CHD who were
      given nutritional counselling by family physicians experienced significant weight
      loss, reduction of waist circumference and body mass index, a significant
      increase in high-density lipoprotein cholesterol, and a significant reduction in
      the risk of developing cardiovascular disease. CONCLUSIONS: By providing
      nutritional counselling, physicians can serve as a source for current information
      and help to correct long-held misperceptions that patients may have regarding
      diet.

PMID- 19751452
TI  - Insulin intensification--the rationale and the target.
AB  - AIMS: To review the key evidence supporting targets for glycaemic control in
      people with type 2 diabetes and the implications for management in primary care.
      METHOD: Literature review. RESULTS: Achieving early glycaemic control may reduce
      long-term risk by minimising the 'metabolic memory' effect of hyperglycaemia.
      Several large studies have failed to confirm expectations that intensive
      treatment would offer greater reductions in risk. This may reflect the failure to
      achieve control blood glucose early in the course of diabetes. Management
      guidelines emphasise the importance of targets for glycaemic control, but differ
      in the strategies they recommend for dose intensification. All, however,
      acknowledge the importance of individualising treatment. CONCLUSION: Early
      achievement of targets for glycaemic control may be important to reduce long-term
      risk in people with diabetes, but treatment should be tailored to individual
      need.

PMID- 19751453
TI  - Barriers to insulin initiation and intensification and how to overcome them.
AB  - AIMS: To review published evidence and clinical experience of the perceived
      barriers to insulin initiation and intensification and to develop solutions for
      patient management. METHOD: Literature review and workshop discussions. RESULTS:
      Many patients with diabetes fail to achieve targets for glycaemic control because
      of inappropriate use of insulin. Patients and health care professionals face many
      potential barriers to insulin initiation and intensification in primary care.
      These can be categorised as low motivation, lack of familiarity or experience and
      time constraints. CONCLUSION: Solutions should be tailored to different health
      care settings. Strategies include improving education and training, providing
      prescribing aids and increasing the efficiency of collaborative working and
      communications.

PMID- 19751454
TI  - Intensification with prandial insulin.
AB  - AIMS: Many patients with type 2 diabetes will ultimately need insulin therapy to
      maintain their target for glycaemic control. This review considers how best to
      achieve the target for glycaemic control in primary care. METHODS: Literature
      review and workshop discussions among participants at the Insulin Intensification
      Summit. RESULTS: Treatment aimed at reducing postprandial glucose is more
      effective in improving glycaemic control near target levels. Adding prandial
      doses of a short-acting insulin is superior to switching to a twice-daily
      premixed insulin. Short-acting analogue insulins offer advantages over animal
      insulins for intensification of basal insulin therapy, which can be achieved
      either by sequentially adding prandial doses or immediate introduction of three
      times daily prandial dose. Each approach has benefits depending on the health
      care system and can be supported in primary care by a simple algorithm.
      CONCLUSION: Intensification of basal insulin therapy is most effectively achieved
      by adding a prandial short-acting insulin analogue, using a simple clinical
      algorithm. The regimen should be selected according to local needs.

PMID- 19751455
TI  - A dramatic addition to the Journal of Clinical Hypertension.

PMID- 19751456
TI  - The role of chlorthalidone in patients with high-risk hypertension.

PMID- 19751457
TI  - Prevention of heart failure with chlorthalidone in ALLHAT: placing the results
      into perspective.

PMID- 19751458
TI  - Heart failure in ALLHAT: did blood pressure medication at study entry influence
      outcome?
AB  - J Clin Hypertens (Greenwich). 2009;11:466-474. (c)2009 Wiley Periodicals,
      Inc.Lower heart failure (HF) rates in individuals taking chlorthalidone vs
      amlodipine, lisinopril, or doxazosin were unanticipated in the Antihypertensive
      and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). HF
      differences appeared early, leading to questions about the possible influence of
      pre-enrollment antihypertensive drugs. A post hoc study evaluated hospitalized HF
      events. During year 1479 individuals had HF, with pre-entry antihypertensive
      medication data obtained on 301 patients (63%). Case-only analysis examined
      interactive effects (interaction odds ratio [OR, ratio of ORs]) of previous
      medication and ALLHAT treatment on HF outcomes, eg, did treatment effect differ
      by pre-entry antihypertensive class? Among cases, 39%, 37%, 17%, and 47% were
      taking pre-entry diuretics, angiotensin-converting enzyme inhibitors, beta
      blockers, and calcium channel blockers, respectively. Interaction OR for year 1
      HF for amlodipine vs chlorthalidone for patients taking vs not taking diuretics
      pre-entry was 1.08 (95% confidence interval [CI], 0.53-2.21; P=.83); for
      lisinopril vs chlorthalidone, 1.33 (95% CI, 0.65-2.74; P=.44); and for doxazosin
      vs chlorthalidone, 1.13 (95% CI, 0.57-2.25; P=.73). Controlling for other pre
      entry antihypertensives yielded similar results. There was no significant
      evidence that pre-entry drug type explained observed hospitalized HF differences
      by ALLHAT treatment.

PMID- 19751459
TI  - Efficacy and safety of long-term treatment with the combination of amlodipine
      besylate and olmesartan medoxomil in patients with hypertension.
AB  - J Clin Hypertens (Greenwich). 2009;11:475-482. (c) 2009 Wiley Periodicals,
      Inc.The authors report on the 44-week open-label extension of the 8-week, double
      blind Combination of Olmesartan Medoxomil and Amlodipine Besylate in Controlling
      High Blood Pressure (COACH) trial in 1684 patients. Initial therapy was
      amlodipine (AML) plus olmesartan medoxomil (OM) 5+40 mg/d, up-titrated to AML+OM
      10+40 mg/d plus hydrochlorothiazide (HCTZ) 12.5 mg then 25 mg if patients did not
      achieve blood pressure (BP) goal (<140/90 mm Hg or <130/80 mm Hg in patients with
      diabetes). Baseline mean BP decreased from 164/102 mm Hg to 131/82 mm Hg at end
      of study, with an overall 66.7% of patients, including those with diabetes,
      achieving BP goal. The BP goal achievement was 80% for AML+OM 5+40 mg/d, 70.6%
      for AML+OM 10+40 mg/d, 66.6% for AML+OM+HCTZ 10+40+12.5 mg/d, and 46.3% for
      AML+OM+HCTZ 10+40+25 mg/d. Study medication was safe and well tolerated.
      Combination antihypertensive therapy with AML+OM+/-HTCZ, up-titrated as
      necessary, allowed a majority of patients to achieve BP goal.

PMID- 19751460
TI  - Insulin resistance and risk of incident hypertension among men.
AB  - J Clin Hypertens (Greenwich). 2009;11:483-490. (c) 2009 Wiley Periodicals,
      Inc.The independent association between insulin resistance and the development of
      hypertension remains in doubt because insulin resistance correlates with other
      metabolic factors also proposed to be associated with hypertension. The authors
      examined the association between the insulin sensitivity index and incident
      hypertension in a prospective nested case-control study among 1453 men (mean age,
      61 years) who participated in the Health Professionals' Follow-up Study. The
      authors computed the insulin sensitivity index for each man in the study based on
      fasting insulin and triglyceride levels. Logistic regression was performed
      conditioned on age and adjusted for standard hypertension risk factors as well as
      renal function, cholesterol, and uric acid. The insulin sensitivity index was 6%
      lower in the cases compared with the controls (P<.001). The multivariable odds
      ratio for hypertension comparing the lowest with highest quartile of insulin
      sensitivity index was 1.09 (0.71-1.65) among the entire sample. However, the
      association between the insulin sensitivity index and incident hypertension
      differed significantly by age (P interaction <.001). Among men younger than 60
      years, the multivariable odds ratio for the lowest compared with highest quartile
      was 1.93 (1.01-3.71) but was 0.67 (0.37-1.24) among older men. Insulin resistance
      is independently associated with incident hypertension among younger men.

PMID- 19751461
TI  - The clinical spectrum of labile hypertension: a management dilemma.
AB  - J Clin Hypertens (Greenwich). 2009;11:491-497. (c)2009 Wiley Periodicals,
      Inc.Although the management of the labile component of blood pressure elevation
      is a problem often encountered by clinicians, there is a paucity of information
      available to guide therapeutic decisions. This review discusses the clinical
      relevance of blood pressure lability, the limitations of current knowledge, and
      possible directions for future research and clinical management.

PMID- 19751462
TI  - A case report: can altitude change blood pressure that much?

PMID- 19751465
TI  - Joint publication of journal of the CardioMetabolic Syndrome and the Journal of
      Clinical Hypertension.

PMID- 19751466
TI  - The relationship between the cardiometabolic syndrome and coronary artery calcium
      progression.
AB  - J Clin Hypertens (Greenwich). 2009;11:505-511. (c)2009 Wiley Periodicals,
      Inc.Cardiometabolic syndrome has been associated with increased likelihood and
      extent of coronary artery calcium (CAC). The authors examined the relationship of
      cardiometabolic syndrome to CAC progression in 200 healthy men who volunteered to
      undergo repeated electron beam tomography separated by 4.2+/-1.3 years.
      Prediction of clinically significant CAC progression (>/=15% per year) was
      evaluated using multivariable logistic regression models and principal component
      analysis. Clinically significant CAC progression was observed in 52.5% of the
      cohort, with the mean and median rate of annual progression 41.3% and 18.3%,
      respectively. The cardiometabolic syndrome in clinically significant CAC
      progression participants was significantly higher compared with those without CAC
      progression (24.8% vs 11.6%; P=.016). Cardiometabolic syndrome was a significant
      independent predictor of clinically significant CAC progression (odds ratio,
      2.65; P=.022). Cardiometabolic syndrome is associated with the baseline CAC
      score, and independently associated with the progression of CAC over 4 years.

PMID- 19751467
TI  - Prevention of type 2 diabetes mellitus to reduce cardiovascular morbidity and
      mortality: a review of the evidence.
AB  - J Clin Hypertens (Greenwich). 2009;11:512-519. (c)2009 Wiley Periodicals,
      Inc.Cardiovascular disease accounts for the majority of deaths in patients with
      type 2 diabetes mellitus. Lifestyle interventions aimed at weight loss and
      increased physical activity and therapy with antidiabetic drugs have proven
      effective in reducing the risk of new-onset diabetes in high-risk individuals.
      Substantial evidence also suggests that drugs that inhibit the renin-angiotensin
      system, namely angiotensin-converting enzyme inhibitors and angiotensin II
      receptor blockers, also prolong the time to onset of clinical diabetes. An open
      question is whether delay of new-onset diabetes with antidiabetic or
      antihypertensive agents reduces cardiovascular morbidity and mortality. A large
      ongoing study is investigating whether therapy with an oral antidiabetic drug or
      an angiotensin II receptor blocker reduces the incidence of new-onset diabetes
      and cardiovascular events in high-risk patients.

PMID- 19751468
TI  - The obesity, metabolic syndrome, and type 2 diabetes mellitus pandemic: II.
      Therapeutic management of atherogenic dyslipidemia.
AB  - J Clin Hypertens (Greenwich). 2009;11:520-527. (c)2009 Wiley Periodicals,
      Inc.Strategies for the effective management of cardiovascular risk factors in
      patients with the metabolic syndrome (MS) or type 2 diabetes mellitus (T2DM) are
      essential to help reduce cardiovascular morbidity and mortality. Treatment
      strategies should be multifactorial and include the promotion of therapeutic
      lifestyle changes, as well as pharmacologic therapies to treat individual risk
      factors according to current guidelines. In an accompanying article, the
      importance of atherogenic dyslipidemia as a risk factor for the development of
      cardiovascular disease in patients with MS or T2DM was highlighted. Current
      treatment options for managing this characteristic form of atherogenic
      dyslipidemia are limited and tend to be only moderately effective. The focus of
      this review is the current pharmacotherapies available for the management of
      atherogenic dyslipidemia in patients with the MS or T2DM, highlighting the
      rationale for combining available treatments. Novel strategies currently in
      clinical development are also discussed.

PMID- 19751469
TI  - 1H-magnetic resonance spectroscopy for quantifying myocardial lipid content in
      humans with the cardiometabolic syndrome.

PMID- 19751470
TI  - Protein-energy malnutrition as a risk factor for visceral leishmaniasis: a
      review.
AB  - The protein-energy malnutrition (PEM) and visceral leishmaniasis (VL) are
      important problems of public health, which affect millions of people worldwide.
      Currently, it has been accepted that the immunity or susceptibility to infect
      parasitic diseases are directly related to the nutritional status of the host.
      However, the mechanisms that govern the relationship between the PEM and the
      course of the VL are multiple and little explained. In this study the current
      most important aspects and the synergism between these two illnesses were
      presented. Bibliographic search includes empirical reports, reviews,
      commentaries, reports from professional associations, books, editorials and
      annals of congress published in diverse languages between 1960 and January 2009.
      As much the PEM as the infections caused by parasites of the Leishmania genus are
      frequent problems in the current days. As new studies are developed on the
      subject, it becomes essential that the society knows them.

PMID- 19751471
TI  - Regulatory T Cells in children with intestinal parasite infection.
AB  - Chronic intestinal parasite infection can induce both persistent immune
      activation and defective responsiveness of T cells. This study aimed to assess
      the number and function of T regulatory (Treg) cells in children with intestinal
      parasite infection. We have studied the peripheral blood from 93 children, 53 of
      them parasitized with protozoa, helminths, or both; the remainder were non
      parasitized, healthy controls. The number and function of CD4(+) CD25(high) and
      CD4(+) Foxp3(+) cells were similar in parasitized and control children. In
      contrast, there was a significant increase in the levels of CD3(+) CD69(+),
      CD4(+) CTLA-4(+), and CD8(+) CD28(-) T cells in helminth infected children.
      Moreover, some of these patients showed a diminished response to CD3/CD28
      stimulation in comparison with the control children. Our data strongly suggest
      that whilst Treg cells are not affected by intestinal parasite infection, CD3(+)
      CD69(+), CD4(+) CTLA-4(+) and CD8(+) CD28(-) lymphocytes may play an important,
      but as yet undetermined role in the diminished immune competence observed in
      parasitized children.

PMID- 19751472
TI  - Adjuvant effect of LPS and killed Propionibacterium acnes on the development of
      experimental gastrointestinal nematode infestation in sheep.
AB  - Gastrointestinal helminthic infection is an important worldwide sheep disease.
      The emergence of anthelminthic resistance has led to drives to seek new means of
      therapeutic control of helminthiasis in sheep. Several data demonstrated the
      adjuvant effect of Propionibacterium acnes on resistance to infection. Herein, we
      evaluate the adjuvant effect of the commercial suspension containing LPS and P.
      acnes on experimental helminthiasis. Sheep received three doses of LPS and P.
      acnes commercial suspension or saline 0.9% (control group). Both groups received
      orally Haemonchus contortus infective larvae on day 0. Parasitological,
      haematological, lymphoproliferation analysis, IL-5 and IgE determination were
      made once a week until 35th day after infection. Our results revealed increase on
      packed cell volumes on day 14, in LPS + P. acnes treated group. On 21st and 35th
      days after infection in the same group occurred increase on circulating
      eosinophils and lymphocytes, and also in the lymphoproliferative response to
      mitogen. On 35th day, the faecal eggs peak in LPS + P. acnes treated group was
      significantly lower than control. A negative correlation between faecal eggs
      counts and circulating eosinophils in the immunostimulant treated group was also
      observed. Our findings suggest that LPS + P. acnes suspension can be used as a
      strategy to control helminthiasis in sheep.

PMID- 19751473
TI  - IL-10 and TGF-beta1 are associated with variations in fluke burdens following
      experimental fasciolosis in sheep.
AB  - Infection with Fasciola hepatica causes an economically important disease in
      ruminants. Variability in parasite load may indicate innate differences in the
      host immune system. This study aimed to investigate the immunological mechanisms
      that are associated with variability in parasite burden following experimental F.
      hepatica infection in cross-bred sheep. Of a total of 16 animals, four were
      randomly chosen as uninfected controls, and the remainder infected with 100
      viable metacercariae. Uninfected animals were used as the control group for
      evaluation of cytokine gene expression levels. For comparative analysis, specific
      animals were selected on the basis of extremes of fluke burdens, and were
      categorised into light (n = 4) and heavy burdened (n = 3) cohorts. Serum antibody
      levels, haematological parameters, and expression of IL-4 and IFN-gamma genes in
      hepatic lymph nodes were equivalent in both groups. However, significant
      differences in mitogen-specific lymphocyte proliferation in vitro and in
      expression of TGF-beta1 and IL-10 genes in hepatic lymph nodes were observed at
      acute and chronic phases of infection, respectively. These results provide useful
      information in developing further understanding of natural resistance to
      fasciolosis in sheep.

PMID- 19751474
TI  - Antileishmanial and immunomodulatory activity of Xylopia discreta.
AB  - This study aimed at determining the in vitro antileishmanial activity of the
      essential oil and eight extracts obtained from Xylopia discreta. J774 and U937
      macrophages were exposed to the different substances to establish the median
      lethal concentration (LC(50)). The median effective concentration (EC(50)) was
      obtained by determining the reduction of Leishmania panamensis-infected cells. A
      selectivity index (SI) (LC(50)/EC(50)) >or= 20 defined a specific activity for
      one Xylopia discreta leaf extracts and for the essential oil, being these the two
      that showed the highest activity (SI = 64.8 and 110, respectively in J774 cells).
      To assess the substances' immunomodulatory activity, pro- and anti-inflammatory
      soluble mediators produced after treating infected macrophages were quantified by
      flow cytometry. The leaf methanol extract and the essential oil induced a
      differential production of monocyte chemoattractant protein-1, a chemokine
      associated with a Leishmania-resistant phenotype (Th1).

PMID- 19751475
TI  - Major role for CD8 T cells in the protection against Toxoplasma gondii following
      dendritic cell vaccination.
AB  - Toxoplasma gondii is the causative agent of toxoplasmosis, a worldwide zoonosis
      for which an effective vaccine is needed. Vaccination with pulsed dendritic cells
      is very efficient but their use in a vaccination protocol is unconceivable.
      Nevertheless, unravelling the induced effector mechanisms is crucial to design
      new vaccine strategies. We vaccinated CBA/J mice with parasite extract-pulsed
      dendritic cells, challenged them with T. gondii cysts and carried out in vivo
      depletion of CD4(+) or CD8(+) T lymphocytes to study the subsequent cellular
      immune response and protective mechanisms. CD4(+) lymphocytes were poorly
      implicated either in spleen and mesenteric lymph node (MLN) cytokine secretion or
      in mice protection. By contrast, the increasing number of intracerebral cysts and
      depletion of CD8(+) cells were strongly correlated, revealing a prominent role
      for CD8(+) lymphocytes in the protection of mice. Splenic CD8(+) lymphocytes
      induce a strong Th1 response controlled by a Th2 response whereas CD8(+) cells
      from MLNs inhibit both Th1 and Th2 responses. CD8(+) cells are the main effectors
      following dendritic cell vaccination and Toxoplasma infection while CD4(+) T
      cells only play a minor role. This contrasts with T. gondii infection which
      elicits the generation of CD4(+) and CD8(+) T cells that provide protective
      immunity.

PMID- 19751476
TI  - Suppression of dendritic cell maturation by Trichinella spiralis
      excretory/secretory products.
AB  - Evidence from experimental studies indicates that during chronic infections with
      certain helminth species a regulatory network is induced that can down-modulate
      not only parasite-induced inflammation but also reduce other immunopathologies
      such as allergies and autoimmune diseases. The mechanisms however, and the
      molecules involved in this immunomodulation are unknown. Here, we focus on the
      effect of Trichinella spiralis excretory/secretory antigens (TspES) on the innate
      immune response by studying the effect of TspES on DC maturation in vitro. Bone
      marrow-derived DC from BALB/c mice were incubated with TspES either alone or in
      combination with LPS derived from two different bacteria. As indicators of DC
      maturation, the cytokine production (IL-1alpha, IL-6, IL-10, IL-12p70 and TNF
      alpha) and the expression of various surface molecules (MHC-II, CD40, CD80 and
      CD86) were measured. Results indicate that while TspES alone did not change the
      expression of the different surface molecules or the cytokine production, it
      completely inhibited DC maturation induced by Escherichia coli LPS (E. coli LPS).
      In contrast, DC maturation induced by LPS from another bacterium, Neisseria
      meningitidis, was not affected by TspES. These results were confirmed using
      TLR4/MD2/CD14 transfected HEK 293 cells. In conclusion, T. spiralis ES antigens
      lead to suppression of DC maturation but this effect depends on the type of LPS
      used to activate these cells.

PMID- 19751477
TI  - Foxp3 expression in lesions of the different clinical forms of American
      tegumentary leishmaniasis.
AB  - As the diversity in clinical presentation of American tegumentary leishmaniasis
      (ATL) is determined mainly by the immune response of host, our aim was to
      evaluate the in situ expression of Foxp3 [marker of regulatory T (Treg) cell] in
      lesions of the different clinical forms of ATL. Foxp3(+) cells were observed in
      39.5% (32/81) of the samples and the number of positive cells was low in all the
      clinical forms. Even presenting a significantly lower number of CD4(+) T cells,
      diffuse cutaneous leishmaniasis (DCL) showed a higher expression of Foxp3 when
      compared with localized cutaneous leishmaniasis (LCL) and mucocutaneous
      leishmaniasis (MCL). In LCL and MCL, the number of Foxp3(+) cells correlated
      positively with the number of apoptotic cells (active caspase-3(+) cells). A
      positive correlation was also observed between the expression of active caspase-3
      and FasL in these clinical forms. Our data suggest that increased number of Treg
      cells may be associated to the hyporesponsiveness observed in DCL and also
      indicate that the apoptosis may be a possible mechanism of action of Foxp3(+)
      Treg cell in LCL and MCL. However, further studies are required to better
      understand the mechanism of action of Treg cell.

PMID- 19751478
TI  - Point: a prescription to decrease left ventricular function.
AB  - The Courage Trial, published in 2007, has significantly reduced the incidence of
      treating stable angina with angioplasty. The investigators randomized 2297
      patients with documented cardiac ischemia to conservative or invasive therapy and
      concluded that there was no difference in major events during a follow-up of 2.5
      to 7 years and that the urge to open the narrowed artery was unjustified. Over
      the years it has been well documented by myocardial biopsy that repeated ischemic
      episodes result in replacement of myocardial cells by fibrous tissue, loss of
      mitochondria, and deterioration of left ventricular function. Ischemic episodes
      often occur in the absence of angina so that it is impossible to determine
      whether the therapy is reducing the magnitude or duration of the process. Also,
      in their study, 32% of the conservatively treated patients crossed over to
      invasive. The evidence indicated that conservative treatment may result in a
      progressive decrease in left ventricular function.

PMID- 19751479
TI  - Counterpoint: Mechanical treatment of atherosclerosis is not a cure.

PMID- 19751480
TI  - Diagnosis, treatment, and referral of hypertension in an emergency department.
AB  - The authors prospectively audited 500 randomly selected charts of patients seen
      during a 6-month period ending in October 2008, in the emergency department of a
      university medical center for the prevalence of hypertension and how it was
      managed. Of the 187 patients with hypertension, 14 (8%) were treated for
      hypertension in the emergency department and 99 (53%) were hospitalized or
      referred to a physician or clinic for follow-up of their hypertension. Much
      improvement is needed, especially since many of the patients seen in the
      emergency department do not have a primary care physician.

PMID- 19751481
TI  - An investigation of pre-activity cardiovascular screening procedures in
      health/fitness facilities--part II: rationale for low adherence with national
      standards.
AB  - The purpose of this study was to explore the rationale provided by program
      directors and general managers of health/fitness facilities for low adherence to
      nationally accepted standards related to pre-activity cardiovascular screening
      procedures (PACSPs) for members and clients of personal trainers. Qualitative
      interviews were conducted with the directors/managers in a Midwest region
      representing 76 facilities who indicated they did not conduct PACSPs for members
      and clients of personal trainers. Analysis of the rationale provided revealed 6
      major clusters: (1) Purpose or need for screening; (2) time and staffing; (3)
      barrier to participation; (4) personal responsibility for health and actions; (5)
      legal issues; and (6) company or franchise policy that categorized the reasons
      for low adherence to PACSPs. These findings highlight the need to increase
      awareness of the relevance of PACSPs among health/fitness managers, staff
      members, and current exercise science students as well as engage those in risk
      management for informed dialogue for consistent application of the standard of
      care.

PMID- 19751482
TI  - Left ventricular geometric patterns in normotensive type 2 diabetic patients in
      Nigeria: an echocardiographic study.
AB  - Left ventricular hypertrophy has been linked with diabetes mellitus and abnormal
      glucose tolerance in several studies. Most previous studies have been carried out
      in the western world with dearth of data in native Africans. A total of 122 type
      2 diabetic patients with a mean age of 55.0+/-8.5 years and another 90 normal
      patients with a mean age of 55.4+/-8.7 years were recruited for the study. Two
      dimensional guided M-mode echocardiography was performed on each patient. In the
      diabetic patients, 49.2% had normal geometry, 23.0% had concentric hypertrophy,
      13.0% had concentric remodeling, and 14.8% had eccentric hypertrophy. In the
      control group, 72.2% had normal geometry, 4.4% had concentric hypertrophy, 11.2%
      had concentric remodeling, and 12.2% had eccentric hypertrophy. In a multiple
      regression analysis, there was significant difference in the geometric pattern of
      the diabetics and controls (chi(2)=11.09, P<.001). Diabetes mellitus is
      independently associated with left ventricular structural changes in Nigerian
      diabetics.

PMID- 19751483
TI  - Cardiovascular risk in special populations II: hypertension.

PMID- 19751484
TI  - Fifth Pivotal Research in Cardiology in the Elderly (PRICE-V) symposium:
      preventive cardiology in the elderly-executive summary. Part I: morning session.

PMID- 19751485
TI  - ACTIVE A and AURORA.

PMID- 19751486
TI  - Evaluation of the Perkins handheld applanation tonometer in the measurement of
      intraocular pressure in dogs and cats.
AB  - OBJECTIVE: To evaluate and to validate the accuracy of the Perkins handheld
      applanation tonometer in the measurement of IOP in dogs and cats. ANIMALS: Twenty
      eyes from 10 dogs and 10 cats immediately after sacrifice were used for the
      postmortem study and 20 eyes from 10 clinically normal and anesthetized dogs and
      cats were used for the in vivo study. Both eyes of 20 conscious dogs and cats
      were also evaluated. PROCEDURE: Readings of IOP postmortem and in vivo were taken
      using manometry (measured with a mercury column manometer) and tonometry
      (measured with a Perkins handheld applanation tonometer). The IOP measurement
      with Perkins tonometer in anesthetized and conscious dogs and cats was
      accomplished by instillation of proxymetacaine 0.5% and of 1% fluorescein eye
      drops. RESULTS: The correlation coefficient (r(2)) between the manometry and the
      Perkins tonometer were 0.982 (dogs) and 0.988 (cats), and the corresponding
      linear regression equation were y = 0.0893x + 0.1105 (dogs) and y = 0.0899x +
      0.1145 (cats) in the postmortem study. The mean IOP readings with the Perkins
      tonometer after calibration curve correction were 14.9 +/- 1.6 mmHg (range 12.2
      17.2 mmHg) in conscious dogs, and were 15.1 +/- 1.7 mmHg (range 12.1-18.7 mmHg)
      in conscious cats. CONCLUSION: There was an excellent correlation between the IOP
      values obtained from direct ocular manometry and the Perkinstonometer in dogs and
      cats. The Perkins handheld tonometer could be in the future a new alternative for
      the diagnosis of glaucoma in veterinary ophthalmology.

PMID- 19751487
TI  - Retinal degeneration in the Abyssinian and Somali cat (rdAc): correlation between
      genotype and phenotype and rdAc allele frequency in two continents.
AB  - OBJECTIVE: To characterize hereditary retinal degeneration in the Abyssinian cat
      (rdAc) in a recently established closed colony segregating for the rdAc mutation,
      and evaluate possible differences in the age of onset and progression of disease
      phenotype since the initial description of rdAc 25 years ago. The sample size of
      an earlier study was increased in order to determine the allele frequency in
      Abyssinian and Somali cats on a worldwide basis. ANIMALS STUDIED: Twenty rdAc
      affected cats from the closed animal facility, 87 Abyssinian and Somali cats for
      study of genotype-phenotype concordance, and DNA from 131 Abyssinian and Somali
      cats from Scandinavia, the UK and Australia for evaluation of the rdAc allele
      frequency. PROCEDURES: DNA was extracted from blood and buccal swabs using
      commercially available kits, followed by genotyping. Ophthalmic examinations were
      performed in the USA and Sweden by two board-certified veterinary
      ophthalmologists. RESULTS: A greater variation in the age of onset and
      progression of the disease was observed compared to that previously described. An
      excellent correlation between genotype and phenotype was observed. A population
      genetic survey revealed that the rdAc allele is in moderate abundance in the
      Abyssinian breed in Europe and Australia. Surprisingly, homozygosity for the
      mutant allele was observed in a Siamese cat with ophthalmoscopic findings similar
      to those originally described for affected rdAc individuals. CONCLUSIONS:
      Alertness to the potential of rdAc is needed on the part of the veterinary
      ophthalmology community, not only in Abyssinian and Somali cats but possibly also
      in other related cat breeds.

PMID- 19751488
TI  - The Dominant white mutation in the PMEL17 gene does not cause visual impairment
      in chickens.
AB  - OBJECTIVE: To examine whether the Dominant white mutation (causing a
      hypopigmented phenotype in chicken) affects the visual ability and gives rise to
      ocular abnormalities in chickens (Gallus gallus). PROCEDURE: Chickens homozygous
      for either the Dominant white mutation or the wild-type alleles were tested in a
      visual contrast behavioral test and subjected to histological and ophthalmologic
      examination. RESULTS: There were no differences between the genotypes in the
      visual contrast behavioral test, and there were no abnormal structures among the
      Dominant white chickens in the ophthalmic examination. The histological sections
      from the Dominant white chickens did not differ from the wild-type chicken in
      structure, photoreceptor density, or RPE pigmentation. CONCLUSIONS: The results
      indicate that the Dominant white mutation in PMEL17 does not seem to affect the
      visual ability or eye structures in chickens.

PMID- 19751489
TI  - Three hundred and three dogs with cataracts seen in Rio de Janeiro, Brazil.
AB  - OBJECTIVE: To describe the most common canine breeds affected with cataracts in
      Rio de Janeiro. ANIMALS: Three hundred and three dogs were included in this
      retrospective study. Animal ages ranged from 6 months to 14.8 years. MATERIAL AND
      METHODS: All records of dogs seen by the Ophthalmology Service of Policlinica
      Veterinaria Botafogo between January 2005 and June 2008 were reviewed. Animals
      with cataracts were separated, and breed and age were evaluated. RESULTS: Most of
      the dogs presented with cataracts were Toy Poodles with a mean age of 8.2 years,
      followed by Cocker Spaniels and Bichon Frises. The percentage of Toy Poodles
      affected with cataracts was 13.8% while 33.3% of Bichon Frise was diagnosed with
      cataracts. CONCLUSIONS: Toy Poodles are a popular breed in Rio de Janeiro.
      Without regulations on breeding, the prevalence of cataracts may increase
      rapidly. Furthermore, due to the relatively late onset of cataract formation in
      the Toy Poodle (mean 8.2 years of age), affected animals may have produced
      several litters of puppies. This study emphasizes the importance of screening for
      the presence of inherited ocular abnormalities such as cataracts prior to
      breeding.

PMID- 19751490
TI  - Daytime profile of the intraocular pressure and tear production in normal dog.
AB  - OBJECTIVE: To evaluate the circadian rhythms of intraocular pressure (IOP) and
      tear production in dog exposed to a natural photoperiod. ANIMALS STUDIED: We used
      12 clinically healthy Beagles dog housed under natural photoperiod at indoor
      temperature and humidity. PROCEDURE: Intraocular pressure and Schirmer tear test
      (STT) I were measured every 4 h over a 48-h period in both eyes in each animal.
      Statistical analysis of the data was performed by one-way repeated-measures
      anova, Student's t-test, and single cosinor method. RESULTS: On each day, there
      was a highly significant effect of time on both parameters. A statistically
      significant difference of STT I values was observed comparing left and right eyes
      (P < 0.0001). Robust daily rhythms were observed for both parameters, IOP values
      showed diurnal acrophase (left eye: 09:33 +/- 00:50 h; right eye: 09:25 +/- 00:22
      h), while STT I values showed nocturnal acrophase (left eye: 20:27 +/- 00:46 h;
      right eye: 20:00 +/- 00:05 h). CONCLUSION: This study has demonstrated circadian
      rhythms in both IOP and STT I.

PMID- 19751491
TI  - Iris abscesses with and without intralenticular fungal invasion in the horse.
AB  - OBJECTIVE: To describe clinical and histologic findings in horses with iris
      abscesses. Design Retrospective medical records study. ANIMALS STUDIED: Medical
      records of horses that had iris abscesses at the University of Florida Veterinary
      Medical Center, Peterson & Smith Equine Hospital, and Veterinary Eye Specialists
      of London, Ontario, from 2005 to 2008 were reviewed. PROCEDURE: Data collected
      from the medical records included signalment, clinical and histologic
      descriptions of ocular lesions, therapy, complications, and visual outcomes.
      RESULTS: The medical records of two Quarterhorses, one pony, one warmblood, one
      Westphalian, and one Arab horse with unilateral iris abscesses were identified.
      Mild-to-severe clinical signs of iridocyclitis were present in all six eyes with
      iris abscesses. The eyes of two horses with iris abscesses were also associated
      with deep stromal abscesses and responded to medical therapy alone in one case,
      and medical therapy and corneal transplantation in the other. Iris abscesses in
      two horses were also associated with intralenticular invasion due to a
      Cladosporium and a Fusarium-type fungus respectively, and resulted in
      enucleations. Two horses with iris abscesses and no apparent lens involvement
      resolved with medical therapy in one case and surgical removal of the iris
      abscess and medical therapy in the other. CONCLUSIONS: This is the first clinical
      report of iris abscesses in the horse, and the first histologic report of fungal
      invasion of the horse lens.

PMID- 19751492
TI  - Ultrasonographic and echobiometric findings in the eyes of Saanen goats of
      different ages.
AB  - OBJECTIVE: To determine ultrasonographic and echobiometric findings in the eyes
      of goats of different ages. B and A mode ultrasonography was performed in 55
      healthy Saanen goats (110 eyes) of ages 45 (n = 15), 180 (n = 20), and 549 days
      (n = 20). PROCEDURES: Transcorneal ultrasonography was performed after
      instillation of a topical anesthetic and application of acoustic transmission gel
      on the 20-MHz linear transducer tip. The transducer was placed in a longitudinal
      position until optimal B scan images, according to echoes of A mode images, were
      obtained. Statistical analysis was carried out to compare the echobiometric
      readings among subjects (P < 0.05). RESULTS: The aqueous and vitreous humors of
      the goats, as well as the lens cortices and nuclei, appeared anechoic. The
      cornea, anterior and posterior lens capsule, sclera, and iris appeared
      hyperechoic and generated peaks on the A mode. Ocular measurements between the
      right and left eyes, as well as between male and female goats were not
      significantly different among subjects of the same age (P = 1.00). All dimensions
      evaluated increased significantly with age (P < 0.01). CONCLUSIONS: The
      ultrasonographic appearances of goat eyes were very similar to those of other
      animal species. The cornea, anterior chamber, lens, vitreous chamber, and axial
      globe length increased with age in the Saanen breed of goats. Knowledge of the
      normal appearance and ocular dimensions of goat eyes facilitates the use of
      ultrasonography in the evaluation of ocular disease in Saanen goats.

PMID- 19751493
TI  - In vitro susceptibility patterns of Aspergillus and Fusarium species isolated
      from equine ulcerative keratomycosis cases in the midwestern and southern United
      States with inclusion of the new antifungal agent voriconazole.
AB  - OBJECTIVE: To evaluate and compare the in vitro susceptibility of Aspergillus and
      Fusarium spp. isolated from horses with ulcerative keratomycosis, address
      regional differences in equine keratomycosis isolates, and provide susceptibility
      data to update prior studies. ANIMAL STUDIED: Fourteen horses with ulcerative
      keratomycosis. PROCEDURES: Banked fungal isolates from equine corneal ulcers
      (eight Aspergillus spp. and six Fusarium spp.) were identified at The University
      of Texas Health Science Center at San Antonio. In vitro minimum inhibitory
      concentration and susceptibility to natamycin, fluconazole, itraconazole,
      voriconazole, ketoconazole, and miconazole were determined for each isolate.
      RESULTS: Fungi were significantly more susceptible to voriconazole than to
      natamycin, itraconazole, fluconazole, and ketoconazole, but miconazole
      susceptibility did not differ significantly from voriconazole. Aspergillus spp.
      were most susceptible to voriconazole, miconazole, and itraconazole, which were
      significantly better to fluconazole and ketoconazole. Fusarium spp.
      susceptibility was greatest to natamycin and voriconazole and lowest to
      itraconazole and ketoconazole. Fusarium spp. were significantly less susceptible
      to itraconazole and ketoconazole compared to natamycin. No significant
      differences in susceptibility were found when isolates from Florida were compared
      with isolates from other states. CONCLUSIONS AND CLINICAL RELEVANCE: Based on in
      vitro evidence, voriconazole appears to be the most effective antifungal for
      initial treatment of equine keratomycosis in the midwestern and southern United
      States. Results are comparable with previous studies in that isolated fungi from
      equine keratomycosis cases showed consistently poor susceptibility to
      fluconazole. Organisms isolated in different geographic locations of the
      midwestern and southern United States appeared to have similar patterns of
      antifungal susceptibility.

PMID- 19751494
TI  - alpha-Luminol prevents decreases in glutamate, glutathione, and glutamine
      synthetase in the retinas of glaucomatous DBA/2J mice.
AB  - OBJECTIVE: To test the hypothesis that in DBA/2J mice, oxidative stress decreases
      glutamine synthetase (GS) levels resulting in a loss of neuronal glutamate and
      that the antioxidant alpha-luminol (GVT) decreases this stress and glutamate loss
      in some types of glaucoma. ANIMALS: DBA/2J mice were separated into two groups,
      of which one was not treated, and the other treated with GVT in the drinking
      water. At 7 months of age, retinas were examined from five untreated DBA/2J mice,
      seven GVT-treated mice, and five C57BL/6 mice (negative controls). METHODS:
      Serial 0.5 microm plastic sections were immunogold stained for glutamate, GS, and
      total glutathione, followed by image analysis for staining patterns and density.
      RESULTS: Focal decreases in glutamate immunostaining were common in the inner
      nuclear layer (INL) of DBA/2J retinas, but not in C57BL/6 or GVT-treated DBA/2J
      retinas. Decreases in glutathione and GS immunostaining were found in DBA/2J
      retinal regions where neuronal glutamate immunostaining was reduced. Retinas from
      GVT-treated DBA/2J had no significant decreases in INL levels of glutamate,
      glutathione, or GS. CONCLUSIONS: Retinas of dogs with primary glaucoma are
      reported to have focal depletion of neuronal glutamate. In DBA/2J mice, similar
      changes occur prior to the development of clinical disease. In these focal
      glutamate-depleted regions, levels of glutathione and GS are also reduced,
      consistent with the hypothesis that oxidative stress contributes to retinal
      changes in glaucoma. The ability of GVT, an antioxidant, to inhibit retinal
      abnormalities in DBA/2J mice provides further support for this hypothesis.

PMID- 19751495
TI  - Central nervous system infection with Staphylococcus intermedius secondary to
      retrobulbar abscessation in a dog.
AB  - In this report, we describe a case of retrobulbar abscessation in a dog that was
      initially diagnosed as masticatory myositis and treated with immunosuppressive
      doses of corticosteroids. Secondary bacterial infection of the central nervous
      system (CNS) occurred and was definitively diagnosed by the analysis and culture
      of the cerebrospinal fluid. This is the first time that retrobulbar infection has
      been definitively shown to result in secondary bacterial infection of the CNS in
      the dog and highlights the importance of ruling out infectious causes of
      retrobulbar disease before assuming and treating for an immune-mediated etiology.

PMID- 19751496
TI  - Bilateral typical complete colobomas in a donkey: retinographic and
      fluorangiographic description.
AB  - An 18-year-old male donkey was referred with a history of blindness. On ocular
      examination a complete bilateral typical colobomatous defect involving iris,
      ciliary body, lens, choroid, retina and optic nerve was observed. An optic pit
      was presented at the temporal side of the right optic head. Ophthalmoscopic and
      fluorangiographic characteristics are described.

PMID- 19751497
TI  - Resveratrol inhibits prostaglandin formation in IL-1beta-stimulated SK-N-SH
      neuronal cells.
AB  - Resveratrol, a polyphenol present in grapes and red wine, has been studied due to
      its vast pharmacological activity. It has been demonstrated that resveratrol
      inhibits production of inflammatory mediators in different in vitro and in vivo
      models. Our group recently demonstrated that resveratrol reduced the production
      of prostaglandin (PG) E2 and 8-isoprostane in rat activated microglia. In a
      microglial-neuronal coculture, resveratrol reduced neuronal death induced by
      activated microglia. However, less is known about its direct roles in neurons. In
      the present study, we investigated the effects of resveratrol on interleukin (IL)
      1beta stimulated SK-N-SH cells. Resveratrol (0.1-5 microM) did not reduce the
      expression of cyclooxygenase (COX)-2 and microsomal PGE2 synthase-1 (mPGES-1),
      although it drastically reduced PGE2 and PGD2 content in IL-1beta-stimulated SK-N
      SH cells. This effect was due, in part, to a reduction in COX enzymatic activity,
      mainly COX-2, at lower doses of resveratrol. The production of 8-iso-PGF2alpha, a
      marker of cellular free radical generation, was significantly reduced by
      resveratrol. The present work provides evidence that resveratrol reduces the
      formation of prostaglandins in neuroblastoma cells by reducing the enzymatic
      activity of inducible enzymes, such as COX-2, and not the transcription of the PG
      synthases, as demonstrated elsewhere.

PMID- 19751499
TI  - The sero-epidemiology of human papillomavirus among Caucasian transplant
      recipients in the UK.
AB  - BACKGROUND: Despite intensive study of high-risk mucosal human papillomaviruses
      (HPV), little is known of the epidemiology of cutaneous HPV. As part of a study
      of cutaneous squamous cell carcinoma and HPV among organ transplant recipients
      (OTR) from London and Oxford, we investigated the seroprevalence and risk factors
      for 34 HPV types (detected using Luminex technology) among 425 Caucasian OTR
      without skin cancer. RESULTS: Overall, 86% of participants were seropositive to
      at least one HPV: 41% to mucosal alpha types, 33% to cutaneous alpha types, 57%
      to alpha types, 56% to beta, 47% to gamma types and 45% to other types (nu, mu,
      HPV101 and 103). In both centres, the most common types were HPV6 (33% and 26%
      for London and Oxford respectively), HPV8 (24% and 18%), HPV15 (26% and 29%),
      HPV17 (25% and 21%), HPV38 (23% and 21%), HPV49 (19% and 21%), HPV4 (27% and
      23%), HPV65 (30% and 25%), HPV95 (22% and 20%), HPV1 (33% and 24%) and HPV63 (28%
      and 17%). The seroprevalence of 8 HPV types differed significantly (P < 0.05)
      between London and Oxford. Those individuals seropositive to multiple types of
      one genus were more likely to be seroreactive to multiple types of another genus.
      As expected, antibodies against mucosal alphaHPV types were more frequent in
      younger patients and among women. Sunbed use and sunbathing was associated with
      seropositivity to multiple gammaHPV (P-trend = 0.007) and self-history of
      abnormal smear was related to seroactivity to multiple betaHPV (P = 0.01). Skin
      type and other self reported markers of exposure to ultraviolet radiation were
      not consistently associated with any HPV types. No other distinguishing
      epidemiological features of transplant recipients with antibodies against single
      or multiple HPV types were identified. CONCLUSION: Findings for mucosal HPV types
      were in line with results from previous studies. We observed differences in HPV
      seroprevalence between organ transplant recipients from two geographically close
      centres but no clear risk factor was found associated with cutaneous HPV
      seropositivity among organ transplant recipients. These findings have
      implications for interpretation of future seroepidemiology studies addressing the
      association between HPV and cutaneous SCC in OTR populations.

PMID- 19751498
TI  - Transcriptome analysis of the responses of Staphylococcus aureus to antimicrobial
      peptides and characterization of the roles of vraDE and vraSR in antimicrobial
      resistance.
AB  - BACKGROUND: Understanding how pathogens respond to antimicrobial peptides, and
      how this compares to currently available antibiotics, is crucial for optimizing
      antimicrobial therapy. Staphylococcus aureus has several known resistance
      mechanisms against human cationic antimicrobial peptides (CAMPs). Gene expression
      changes in S. aureus strain Newman exposed to linear CAMPs were analyzed by DNA
      microarray. Three antimicrobial peptides were used in the analysis, two are
      derived from frog, temporin L and dermaseptin K4-S4(1-16), and the ovispirin-1 is
      obtained from sheep. RESULTS: The peptides induced the VraSR cell-wall regulon
      and several other genes that are also up-regulated in cells treated with
      vancomycin and other cell wall-active antibiotics. In addition to this
      similarity, three genes/operons were particularly strongly induced by the
      peptides: vraDE, SA0205 and SAS016, encoding an ABC transporter, a putative
      membrane-bound lysostaphin-like peptidase and a small functionally unknown
      protein, respectively. Ovispirin-1 and dermaseptin K4-S4(1-16), which disrupt
      lipid bilayers by the carpet mechanism, appeared to be strong inducers of the
      vraDE operon. We show that high level induction by ovispirin-1 is dependent on
      the amide modification of the peptide C-terminus. This suggests that the amide
      group has a crucial role in the activation of the Aps (GraRS) sensory system, the
      regulator of vraDE. In contrast, temporin L, which disrupts lipid bilayers by
      forming pores, revealed a weaker inducer of vraDE despite the C-terminal amide
      modification. Sensitivity testing with CAMPs and other antimicrobials suggested
      that VraDE is a transporter dedicated to resist bacitracin. We also showed that
      SA0205 belongs to the VraSR regulon. Furthermore, VraSR was shown to be important
      for resistance against a wide range of cell wall-active antibiotics and other
      antimicrobial agents including the amide-modified ovispirin-1, bacitracin,
      teicoplanin, cefotaxime and 10 other beta-lactam antibiotics, chlorpromazine,
      thioridazine and EGTA. CONCLUSION: Defense against different CAMPs involves not
      only general signaling pathways but also CAMP-specific ones. These results
      suggest that CAMPs or a mixture of CAMPs could constitute a potential additive to
      standard antibiotic treatment.

PMID- 19751500
TI  - Structured information during the ICU stay to reduce anxiety: study protocol of a
      multicenter randomized controlled trial.
AB  - BACKGROUND: ICU stay is often associated with negative experiences for the
      individual patient. Many patients are disabled and their communication is
      restricted during the ICU stay. Specific information on procedures, sensations
      and coping behavior are thought to reduce anxiety on the ICU. Until now
      information programs to reduce anxiety were mainly delivered preoperatively,
      completely neglecting informational needs of non-elective ICU patients. METHODS:
      The trial is designed as a prospective multicenter randomized controlled trial in
      the cities of Marburg, Halle and Stuttgart. Elective and non-elective ICU
      patients will be included. The trial includes an intervention and a control group
      on the ICU. The control group receives a trivial conversation without any ICU
      specific information. The intervention group receives an information program with
      specific procedural, sensory and coping information about their ICU stay. Both
      conversations take place in the ICU and are planned to take about 10 minutes.
      DISCUSSION: In contrast to former trials on information programs on the ICU-stay
      our intervention will take place in the ICU itself. This approach will ensure to
      compensate for memory effects due to anesthesia or preoperative stress. Further
      the results will be applicable to non-elective ICU-patients. TRIAL REGISTRATION:
      ClinicalTrials NCT00764933.

PMID- 19751501
TI  - The seroprevalence of human papillomavirus by immune status and by ethnicity in
      London.
AB  - BACKGROUND: The natural history of cutaneous HPV is unclear and in particular,
      seroprevalence among individuals with different levels of immune function and
      ethnicity is unknown. As part of a study of cutaneous squamous cell carcinoma
      (SCC) and HPV among organ transplant recipients (OTR) from London, we
      investigated the seroprevalence and risk factors for 34 HPV types (detected using
      Luminex technology) among 409 OTR patients without skin cancer (243 Caucasians
      and 166 non-Caucasians), 367 individuals with end stage renal failure on dialysis
      (222 Caucasians and 145 non-Caucasians) and 152 immunocompetent (IC) individuals
      without skin cancer (102 Caucasians and 50 non-Caucasians) to compare the HPV
      seroprevalence in patients with differing immune status and ethnicity. In total,
      seroprevalence data from 928 individuals, all from London, was available.
      RESULTS: Overall, no difference between HPV seroprevalence by immune status was
      observed (P = 0.3) among Caucasian or among non-Caucasian individuals, with
      seroprevalence varying from 87% to 94% across different immune status and ethnic
      groups. Those individuals seropositive to multiple types of one genus were more
      likely to be seroreactive to multiple types of another genus, independent of
      immune status or ethnicity. Lower seroprevalence for gammaHPV 4, and to a lesser
      extent gammaHPV 48, were observed among OTR compared to IC and dialysis patients.
      Higher seroprevalence against antibodies to betaHPV 93 were detected more
      frequently in non-Caucasians than Caucasians whereas muHPV 1 and, to a lesser
      extent, gammaHPV 4 were found more frequently among Caucasians - these findings
      were independent of immune status. Within non-Caucasian subgroups, the
      seroprevalence of 8 HPV (alpha-mucosal HPV16 and 13, alpha-cutaneous HPV7 and 2,
      betaHPV8, 17, 23 and 38) was significantly (P < 0.02) higher in Black compared to
      Asian patients. HPV16 being sexually transmitted, this might suggest a potential
      sexual route of transmission for some beta HPV types. CONCLUSION: We did not
      observe major disturbance in antibody response between immunocompetent, dialysis
      and OTR individuals, but significant differences in HPV seroprevalence were
      identified according to ethnicity. Further research is needed to clarify the
      natural history of cutaneous HPV, particularly given the growing research
      interest in its possible role in the pathogenesis of cutaneous SCC.

PMID- 19751502
TI  - Impact of first-line protease inhibitors on predicted resistance to tipranavir in
      HIV-1-infected patients with virological failure.
AB  - BACKGROUND: Tipranavir (TPV) is a recently approved nonpeptidic protease
      inhibitor (PI) of HIV-1 and has been indicated for those infected with PIs
      resistant HIV-1. However, in clinical practice, whether the HIV-1 from the
      patients with virological failure to the regimens containing first-line PIs
      remains susceptible to TPV/r may be questionable. METHODS: To assess the
      resistance levels to TPV of HIV-1 from patients with treatment failure to first
      line PIs, patients who experienced virological failure were tested for genotypic
      resistance of HIV-1 since August 2006 in National Taiwan University Hospital.
      Patients were enrolled for this analysis if their failed regimens contained > 12
      weeks of atazanavir or lopinavir/ritonavir (defined as ATV group and LPV/r group,
      respectively), but were excluded if they experienced both or other PIs. The
      levels of genotypic resistance to TPV/r were determined by TPV mutation score.
      RESULTS: Till May 2008, 21 subjects in ATV group and 20 subjects in LPV/r group
      were enrolled. The TPV mutation scores in subjects in LPV/r group were
      significantly higher than these in ATV group (median, 3 vs 1, P = 0.007). 95.2%
      subjects in ATV group and only 45% subjects in LPV/r group had an estimated
      maximal virological response to TPV/r (P < 0.001). The resistance levels to TPV/r
      correlated with the duration of exposure to first-line PIs, whether in ATV or
      LPV/r group. CONCLUSION: Cross-resistance from first-line PIs may impede the
      effectiveness of TPV/r-containing salvage therapy. TPV/r should be used
      cautiously for patients with virological failure to LPV/r especially long
      duration of exposure.

PMID- 19751504
TI  - Response rates in postal surveys of healthcare professionals between 1996 and
      2005: an observational study.
AB  - BACKGROUND: Postal surveys are a frequently used method of data collection in
      health services research. Low response rates increase the potential for bias and
      threaten study validity. The objectives of this study were to estimate current
      response rates, to assess whether response rates are falling, to explore factors
      that might enhance response rates and to examine the potential for non-response
      bias in surveys mailed to healthcare professionals. METHODS: A random sample of
      postal or electronic surveys of healthcare workers (1996-2005) was identified
      from Medline, Embase or Psycinfo databases or Biomed Central. Outcome measures
      were survey response rate and non response analysis. Multilevel, multivariable
      logistic regression examined the relationship between response rate and
      publication type, healthcare profession, country and number of survey
      participants, questionnaire length and use of reminders. RESULTS: The analysis
      included 350 studies. Average response rate in doctors was 57.5% (95%CI: 55.2% to
      59.8%) and significantly lower than the estimate for the prior 10 year period.
      Response rates were higher when reminders were sent (adjusted OR 1.3; 95%CI 1.1
      1.6) but only half the studies did this. Response rates were also higher in
      studies with fewer than 1000 participants and in countries other than US, Canada,
      Australia and New Zealand. They were not significantly affected by publication
      type or healthcare profession (p > 0.05). Only 17% of studies attempted
      assessment of possible non-response bias. CONCLUSION: Response rates to postal
      surveys of healthcare professionals are low and probably declining, almost
      certainly leading to unknown levels of bias. To improve the informativeness of
      postal survey findings, researchers should routinely consider the use of
      reminders and assess potential for non-response bias.

PMID- 19751503
TI  - A review of co-morbidity between infectious and chronic disease in Sub Saharan
      Africa: TB and diabetes mellitus, HIV and metabolic syndrome, and the impact of
      globalization.
AB  - BACKGROUND: Africa is facing a rapidly growing chronic non-communicable disease
      burden whilst at the same time experiencing continual high rates of infectious
      disease. It is well known that some infections increase the risk of certain
      chronic diseases and the converse. With an increasing dual burden of disease in
      Sub Saharan Africa the associations between diseases and our understanding of
      them will become of increased public health importance. AIMS: In this review we
      explore the relationships reported between tuberculosis and diabetes mellitus,
      human immunodeficiency virus, its treatment and metabolic risk. We aimed to
      address the important issues surrounding these associations within a Sub Saharan
      African setting and to describe the impact of globalization upon them. FINDINGS:
      Diabetes has been associated with a 3-fold incident risk of tuberculosis and it
      is hypothesised that tuberculosis may also increase the risk of developing
      diabetes. During co-morbid presentation of tuberculosis and diabetes both
      tuberculosis and diabetes outcomes are reported to worsen. Antiretroviral therapy
      for HIV has been associated with an increased risk of developing metabolic
      syndrome and HIV has been linked with an increased risk of developing both
      diabetes and cardiovascular disease. Globalization is clearly related to an
      increased risk of diabetes and cardiovascular disease. It may be exerting other
      negative and positive impacts upon infectious and chronic non-communicable
      disease associations but at present reporting upon these is sparse. CONCLUSION:
      The impact of these co-morbidities in Sub Saharan Africa is likely to be large.
      An increasing prevalence of diabetes may hinder efforts at tuberculosis control,
      increasing the number of susceptible individuals in populations where
      tuberculosis is endemic, and making successful treatment harder. Roll out of anti
      retroviral treatment coverage within Sub Saharan Africa is an essential response
      to the HIV epidemic however it is likely to lead to a growing number of
      individuals suffering adverse metabolic consequences. One of the impacts of
      globalization is to create environments that increase both diabetes and
      cardiovascular risk but further work is needed to elucidate other potential
      impacts. Research is also needed to develop effective approaches to reducing the
      frequency and health impact of the co-morbidities described here.

PMID- 19751505
TI  - Assessment of global phase uncertainty in case-control studies.
AB  - BACKGROUND: In haplotype-based candidate gene studies a problem is that the
      genotype data are unphased, which results in haplotype ambiguity. The R(h)(2)
      measure 1 quantifies haplotype predictability from genotype data. It is computed
      for each individual haplotype, and for a measure of global relative efficiency a
      minimum R(h)(2) value is suggested. Alternatively, we developed methods directly
      based on the information content of haplotype frequency estimates to obtain
      global relative efficiency measures: R(A)(2) and R(D)(2) based on A- and D
      optimality, respectively. All three methods are designed for single populations;
      they can be applied in cases only, controls only or the whole data. Therefore
      they are not necessarily optimal for haplotype testing in case-control studies.
      RESULTS: A new global relative efficiency measure R(T)(2) was derived to maximize
      power of a simple test statistic that compares haplotype frequencies in cases and
      controls. Application to real data showed that our proposed method R(T)(2) gave a
      clear and summarizing measure for the case-control study conducted. Additionally
      this measure might be used for selection of individuals, who have the highest
      potential for improving power by resolving phase ambiguity. CONCLUSION: Instead
      of using relative efficiency measure for cases only, controls only or their
      combined data, we link uncertainty measure to case-control studies directly.
      Hence, our global efficiency measure might be useful to assess whether data are
      informative or have enough power for estimation of a specific haplotype risk.

PMID- 19751506
TI  - Determining relative importance of variables in developing and validating
      predictive models.
AB  - BACKGROUND: Multiple regression models are used in a wide range of scientific
      disciplines and automated model selection procedures are frequently used to
      identify independent predictors. However, determination of relative importance of
      potential predictors and validating the fitted models for their stability,
      predictive accuracy and generalizability are often overlooked or not done
      thoroughly. METHODS: Using a case study aimed at predicting children with acute
      lymphoblastic leukemia (ALL) who are at low risk of Tumor Lysis Syndrome (TLS),
      we propose and compare two strategies, bootstrapping and random split of data,
      for ordering potential predictors according to their relative importance with
      respect to model stability and generalizability. We also propose an approach
      based on relative increase in percentage of explained variation and area under
      the Receiver Operating Characteristic (ROC) curve for developing models where
      variables from our ordered list enter the model according to their importance. An
      additional data set aimed at identifying predictors of prostate cancer
      penetration is also used for illustrative purposes. RESULTS: Age is chosen to be
      the most important predictor of TLS. It is selected 100% of the time using the
      bootstrapping approach. Using the random split method, it is selected 99% of the
      time in the training data and is significant (at 5% level) 98% of the time in the
      validation data set. This indicates that age is a stable predictor of TLS with
      good generalizability. The second most important variable is white blood cell
      count (WBC). Our methods also identified an important predictor of TLS that was
      otherwise omitted if relying on any of the automated model selection procedures
      alone. A group at low risk of TLS consists of children younger than 10 years of
      age, without T-cell immunophenotype, whose baseline WBC is < 20 x 10(9)/L and
      palpable spleen is < 2 cm. For the prostate cancer data set, the Gleason score
      and digital rectal exam are identified to be the most important indicators of
      whether tumor has penetrated the prostate capsule. CONCLUSION: Our model
      selection procedures based on bootstrap re-sampling and repeated random split
      techniques can be used to assess the strength of evidence that a variable is
      truly an independent and reproducible predictor. Our methods, therefore, can be
      used for developing stable and reproducible models with good performances.
      Moreover, our methods can serve as a good tool for validating a predictive model.
      Previous biological and clinical studies support the findings based on our
      selection and validation strategies. However, extensive simulations may be
      required to assess the performance of our methods under different scenarios as
      well as check their sensitivity to a random fluctuation in the data.

PMID- 19751507
TI  - Transcriptional profiling differences for articular cartilage and repair tissue
      in equine joint surface lesions.
AB  - BACKGROUND: Full-thickness articular cartilage lesions that reach to the
      subchondral bone yet are restricted to the chondral compartment usually fill with
      a fibrocartilage-like repair tissue which is structurally and biomechanically
      compromised relative to normal articular cartilage. The objective of this study
      was to evaluate transcriptional differences between chondrocytes of normal
      articular cartilage and repair tissue cells four months post-microfracture.
      METHODS: Bilateral one-cm2 full-thickness defects were made in the articular
      surface of both distal femurs of four adult horses followed by subchondral
      microfracture. Four months postoperatively, repair tissue from the lesion site
      and grossly normal articular cartilage from within the same femorotibial joint
      were collected. Total RNA was isolated from the tissue samples, linearly
      amplified, and applied to a 9,413-probe set equine-specific cDNA microarray.
      Eight paired comparisons matched by limb and horse were made with a dye-swap
      experimental design with validation by histological analyses and quantitative
      real-time polymerase chain reaction (RT-qPCR). RESULTS: Statistical analyses
      revealed 3,327 (35.3%) differentially expressed probe sets. Expression of
      biomarkers typically associated with normal articular cartilage and
      fibrocartilage repair tissue corroborate earlier studies. Other changes in gene
      expression previously unassociated with cartilage repair were also revealed and
      validated by RT-qPCR. CONCLUSION: The magnitude of divergence in transcriptional
      profiles between normal chondrocytes and the cells that populate repair tissue
      reveal substantial functional differences between these two cell populations. At
      the four-month postoperative time point, the relative deficiency within repair
      tissue of gene transcripts which typically define articular cartilage indicate
      that while cells occupying the lesion might be of mesenchymal origin, they have
      not recapitulated differentiation to the chondrogenic phenotype of normal
      articular chondrocytes.

PMID- 19751508
TI  - Expression analysis of E-cadherin, Slug and GSK3beta in invasive ductal carcinoma
      of breast.
AB  - BACKGROUND: Cancer progression is linked to a partially dedifferentiated
      epithelial cell phenotype. The signaling pathways Wnt, Hedgehog, TGF-beta and
      Notch have been implicated in experimental and developmental epithelial
      mesenchymal transition (EMT). Recent findings from our laboratory confirm that
      active Wnt/beta-catenin signaling is critically involved in invasive ductal
      carcinomas (IDCs) of breast. METHODS: In the current study, we analyzed the
      expression patterns and relationships between the key Wnt/beta-catenin signaling
      components- E-cadherin, Slug and GSK3beta in IDCs of breast. RESULTS: Of the 98
      IDCs analyzed, 53 (54%) showed loss/or reduced membranous staining of E-cadherin
      in tumor cells. Nuclear accumulation of Slug was observed in 33 (34%) IDCs
      examined. Loss or reduced level of cytoplasmic GSK3beta expression was observed
      in 52/98 (53%) cases; while 34/98 (35%) tumors showed nuclear accumulation of
      GSK3beta. Statistical analysis revealed associations of nuclear Slug expression
      with loss of membranous E-cadherin (p = 0.001); nuclear beta-catenin (p = 0.001),
      and cytoplasmic beta-catenin (p = 0.005), suggesting Slug mediated E-cadherin
      suppression via the activation of Wnt/beta-catenin signaling pathway in IDCs. Our
      study also demonstrated significant correlation between GSK3beta nuclear
      localization and tumor grade (p = 0.02), suggesting its association with tumor
      progression. CONCLUSION: The present study for the first time provided the
      clinical evidence in support of Wnt/beta-catenin signaling upregulation in IDCs
      and key components of this pathway - E-cadherin, Slug and GSK3beta with beta
      catenin in implementing EMT in these cells.

PMID- 19751509
TI  - Gene array analysis of adrenal glands in broiler chickens following ACTH
      treatment.
AB  - BACKGROUND: Difference in adaptability responses to stress has been observed
      amongst bird species, strains, and individuals. Components of the HPA axis, one
      of the internal systems involved in homeostasis re-establishment following
      stress, could play a role in this variability of responses. The aim of the
      present study was 1) to identify genes involved in the regulation of adrenal
      activity following ACTH stimulation and 2) to examine adrenal genes
      differentially expressed in individuals with high and low plasma corticosterone
      response following ACTH treatment. RESULTS: Analysis with 21 K poultry oligo
      microarrays indicated that ACTH treatment affected the expression of 134 genes.
      Several transcripts assigned to genes involved in the adrenal ACTH signaling
      pathway and steroidogenic enzymes were identified as differentially expressed by
      ACTH treatment. Real-time PCR on 18 selected genes confirmed changes in
      transcript levels of 11 genes, including MC2R, CREM, Cry, Bmal1, Sqle, Prax1, and
      StAR. Only 4 genes revealed to be differentially expressed between higher and
      lower adrenal responders to ACTH treatment. CONCLUSION: The results from the
      present study reveal putative candidate genes; their role in regulation of
      adrenal functions and adaptability to stress should be further investigated.

PMID- 19751510
TI  - MMP-1 serum levels predict coronary atherosclerosis in humans.
AB  - BACKGROUND: Myocardial infarction results as a consequence of atherosclerotic
      plaque rupture, with plaque stability largely depending on the lesion forming
      extracellular matrix components. Lipid enriched non-calcified lesions are
      considered more instable and rupture prone than calcified lesions. Matrix
      metalloproteinases (MMPs) are extracellular matrix degrading enzymes with plaque
      destabilisating characteristics which have been implicated in atherogenesis. We
      therefore hypothesised MMP-1 and MMP-9 serum levels to be associated with non
      calcified lesions as determined by CT-angiography in patients with coronary
      artery disease. METHODS: 260 patients with typical or atypical chest pain
      underwent dual-source multi-slice CT-angiography (0.6-mm collimation, 330-ms
      gantry rotation time) to exclude coronary artery stenosis. Atherosclerotic
      plaques were classified as calcified, mixed or non-calcified. RESULTS: In
      multivariable regession analysis, MMP-1 serum levels were associated with total
      plaque burden (OR: 1.37 (CI: 1.02-1.85); p < 0.05) in a model adjusted for age,
      sex, BMI, classical cardiovascular risk factors, hsCRP, adiponectin, pericardial
      fat volume and medication. Specification of plaque morphology revealed
      significant association of MMP-1 serum levels with non-calcified plaques (OR:
      1.16 (CI: 1.0-1.34); p = 0.05) and calcified plaques (OR: 1.22 (CI: 1,03-1.45); p
      < 0.05) while association with mixed plaques was lost in the fully adjusted
      model. No associations were found between MMP9 serum levels and total plaque
      burden or plaque morphology. CONCLUSION: MMP-1 serum levels are associated with
      total plaque burden but do not allow a specification of plaque morphology.

PMID- 19751511
TI  - Vascular injuries after blunt chest trauma: diagnosis and management.
AB  - BACKGROUND: Although relatively rare, blunt injury to thoracic great vessels is
      the second most common cause of trauma related death after head injury. Over the
      last twenty years, the paradigm for management of these devastating injuries has
      changed drastically. The goal of this review is to update the reader on current
      concepts of diagnosis and management of blunt thoracic vascular trauma. METHODS:
      A review of the medical literature was performed to obtain articles pertaining to
      both blunt injuries of the thoracic aorta and of the non-aortic great vessels in
      the chest. Articles were chosen based on authors' preference and clinical
      expertise. DISCUSSION: Blunt thoracic vascular injury remains highly lethal, with
      most victims dying prior to reaching a hospital. Those arriving in extremis
      require immediate intervention, which may include treatment of other associated
      life threatening injuries. More stable injuries can often be medically temporized
      in order to optimize definitive management. Endovascular techniques are being
      employed with increasing frequency and can often significantly simplify
      management in otherwise very complex patient scenarios.

PMID- 19751512
TI  - Characterization of human breast cancer epithelial cells (HBCEC) derived from
      long term cultured biopsies.
AB  - INTRODUCTION: For a more individualized therapeutic approach we explored a
      protease-free method to culture primary cells from breast cancer biopsies.
      METHODS AND RESULTS: Tumor tissue from breast cancer patients after surgery was
      cultured ex vivo without enzymatic digestion for more than one year and revealed
      the continuous outgrowth of adherent and proliferating primary cell populations.
      Immunofluorescence staining of these human breast cancer-derived epithelial cells
      (HBCEC) and quantification by flow cytometry revealed nearly exclusively
      cytokeratin-expressing cells. Analysis of surface markers during long term tumor
      culture of primary HBCEC (more than 476d) demonstrated a prominent expression of
      CD24, CD44 and MUC1 (CD227). According to aging markers, expression of senescence
      associated beta-galactosidase revealed little if any positive staining in a
      primary tumor-derived HBCEC population after 722d in culture, whereas the
      majority of normal human mammary epithelial cells (HMEC) demonstrated senescent
      cells already after a culture period of 32d. In this context, HBCEC populations
      derived from a tumor culture after 152d and 308d, respectively, exhibited a
      significant telomerase activity, suggesting continuous proliferative capacity.
      Treatment with several chemotherapeutic compounds and their combinations revealed
      distinct cytotoxic effects among HBCEC from different breast cancer patients,
      indicating an individualized response of these tumor-derived primary cells.
      CONCLUSION: The protease-free outgrowth of primary HBCEC offers a patient
      specific approach to optimize an individually-designed cancer therapy. Moreover,
      HBCEC from long term breast tumor tissue cultures resemble tumor cell-like
      properties by an intact ECM formation and a stable cell surface protein
      expression providing a reproducible screening platform to identify new biomarkers
      and to test new therapeutics in individual tumor samples.

PMID- 19751513
TI  - Epitopia: a web-server for predicting B-cell epitopes.
AB  - BACKGROUND: Detecting candidate B-cell epitopes in a protein is a basic and
      fundamental step in many immunological applications. Due to the impracticality of
      experimental approaches to systematically scan the entire protein, a
      computational tool that predicts the most probable epitope regions is desirable.
      RESULTS: The Epitopia server is a web-based tool that aims to predict immunogenic
      regions in either a protein three-dimensional structure or a linear sequence.
      Epitopia implements a machine-learning algorithm that was trained to discern
      antigenic features within a given protein. The Epitopia algorithm has been
      compared to other available epitope prediction tools and was found to have higher
      predictive power. A special emphasis was put on the development of a user
      friendly graphical interface for displaying the results. CONCLUSION: Epitopia is
      a user-friendly web-server that predicts immunogenic regions for both a protein
      structure and a protein sequence. Its accuracy and functionality make it a highly
      useful tool. Epitopia is available at http://epitopia.tau.ac.il and includes
      extensive explanations and example predictions.

PMID- 19751514
TI  - Comparison of hospital charge prediction models for gastric cancer patients:
      neural network vs. decision tree models.
AB  - BACKGROUND: In recent years, artificial neural network is advocated in modeling
      complex multivariable relationships due to its ability of fault tolerance; while
      decision tree of data mining technique was recommended because of its richness of
      classification arithmetic rules and appeal of visibility. The aim of our research
      was to compare the performance of ANN and decision tree models in predicting
      hospital charges on gastric cancer patients. METHODS: Data about hospital charges
      on 1008 gastric cancer patients and related demographic information were
      collected from the First Affiliated Hospital of Anhui Medical University from
      2005 to 2007 and preprocessed firstly to select pertinent input variables. Then
      artificial neural network (ANN) and decision tree models, using same hospital
      charge output variable and same input variables, were applied to compare the
      predictive abilities in terms of mean absolute errors and linear correlation
      coefficients for the training and test datasets. The transfer function in ANN
      model was sigmoid with 1 hidden layer and three hidden nodes. RESULTS: After
      preprocess of the data, 12 variables were selected and used as input variables in
      two types of models. For both the training dataset and the test dataset, mean
      absolute errors of ANN model were lower than those of decision tree model
      (1819.197 vs. 2782.423, 1162.279 vs. 3424.608) and linear correlation
      coefficients of the former model were higher than those of the latter (0.955 vs.
      0.866, 0.987 vs. 0.806). The predictive ability and adaptive capacity of ANN
      model were better than those of decision tree model. CONCLUSION: ANN model
      performed better in predicting hospital charges of gastric cancer patients of
      China than did decision tree model.

PMID- 19751515
TI  - Array comparative genomic hybridization and flow cytometry analysis of
      spontaneous abortions and mors in utero samples.
AB  - BACKGROUND: It is estimated that 10-15% of all clinically recognised pregnancies
      result in a spontaneous abortion or miscarriage. Previous studies have indicated
      that in up to 50% of first trimester miscarriages, chromosomal abnormalities can
      be identified. For several decades chromosome analysis has been the golden
      standard to detect these genomic imbalances. A major drawback of this method is
      the requirement of short term cultures of fetal cells. In this study we evaluated
      the combined use of array CGH and flow cytometry (FCM), for detection of
      chromosomal abnormalities, as an alternative for karyotyping. METHODS: In total
      100 spontaneous abortions and mors in utero samples were investigated by
      karyotyping and array CGH in combination with FCM in order to compare the results
      for both methods. RESULTS: Chromosome analysis revealed 17 abnormal karyotypes
      whereas array CGH in combination with FCM identified 26 aberrations due to the
      increased test success rate. Karyotyping was unsuccessful in 28% of cases as
      compared to only two out of hundred samples with inconclusive results for
      combined array CGH and FCM analysis. CONCLUSION: This study convincingly shows
      that array CGH analysis for detection of numerical and segmental imbalances in
      combination with flow cytometry for detection of ploidy status has a significant
      higher detection rate for chromosomal abnormalities as compared to karyotyping of
      miscarriages samples.

PMID- 19751516
TI  - Sequelae due to bacterial meningitis among African children: a systematic
      literature review.
AB  - BACKGROUND: African children have some of the highest rates of bacterial
      meningitis in the world. Bacterial meningitis in Africa is associated with high
      case fatality and frequent neuropsychological sequelae. The objective of this
      study is to present a comprehensive review of data on bacterial meningitis
      sequelae in children from the African continent. METHODS: We conducted a
      systematic literature search to identify studies from Africa focusing on children
      aged between 1 month to 15 years with laboratory-confirmed bacterial meningitis.
      We extracted data on neuropsychological sequelae (hearing loss, vision loss,
      cognitive delay, speech/language disorder, behavioural problems, motor
      delay/impairment, and seizures) and mortality, by pathogen. RESULTS: A total of
      37 articles were included in the final analysis representing 21 African countries
      and 6,029 children with confirmed meningitis. In these studies, nearly one fifth
      of bacterial meningitis survivors experienced in-hospital sequelae (median = 18%,
      interquartile range (IQR) = 13% to 27%). About a quarter of children surviving
      pneumococcal meningitis and Haemophilus influenzae type b (Hib) meningitis had
      neuropsychological sequelae by the time of hospital discharge, a risk higher than
      in meningococcal meningitis cases (median = 7%). The highest in-hospital case
      fatality ratios observed were for pneumococcal meningitis (median = 35%) and Hib
      meningitis (median = 25%) compared to meningococcal meningitis (median = 4%). The
      10 post-discharge studies of children surviving bacterial meningitis were of
      varying quality. In these studies, 10% of children followed-up post discharge
      died (range = 0% to 18%) and a quarter of survivors had neuropsychological
      sequelae (range = 3% to 47%) during an average follow-up period of 3 to 60
      months. CONCLUSION: Bacterial meningitis in Africa is associated with high
      mortality and risk of neuropsychological sequelae. Pneumococcal and Hib
      meningitis kill approximately one third of affected children and cause clinically
      evident sequelae in a quarter of survivors prior to hospital discharge. The three
      leading causes of bacterial meningitis are vaccine preventable, and routine use
      of conjugate vaccines could provide substantial health and economic benefits
      through the prevention of childhood meningitis cases, deaths and disability.

PMID- 19751517
TI  - Group treatments for sensitive health care problems: a randomised controlled
      trial of group versus individual physiotherapy sessions for female urinary
      incontinence.
AB  - BACKGROUND: The aim was to compare effectiveness of group versus individual
      sessions of physiotherapy in terms of symptoms, quality of life, and costs, and
      to investigate the effect of patient preference on uptake and outcome of
      treatment. METHODS: A pragmatic, multi-centre randomised controlled trial in five
      British National Health Service physiotherapy departments. 174 women with stress
      and/or urge incontinence were randomised to receive treatment from a
      physiotherapist delivered in a group or individual setting over three weekly
      sessions. Outcome were measured as Symptom Severity Index; Incontinence-related
      Quality of Life questionnaire; National Health Service costs, and out of pocket
      expenses. RESULTS: The majority of women expressed no preference (55%) or
      preference for individual treatment (36%). Treatment attendance was good, with
      similar attendance with both service delivery models. Overall, there were no
      statistically significant differences in symptom severity or quality of life
      outcomes between the models. Over 85% of women reported a subjective benefit of
      treatment, with a slightly higher rating in the individual compared with the
      group setting. When all health care costs were considered, average cost per
      patient was lower for group sessions (Mean cost difference 52.91 pounds 95%,
      confidence interval ( 25.82 pounds- 80.00 pounds)). CONCLUSION: Indications are
      that whilst some women may have an initial preference for individual treatment,
      there are no substantial differences in the symptom, quality of life outcomes or
      non-attendance. Because of the significant difference in mean cost, group
      treatment is recommended. TRIAL REGISTRATION:  TRIAL REGISTRATION NUMBER: ISRCTN
      16772662.

PMID- 19751518
TI  - Genome-wide deletion mutant analysis reveals genes required for respiratory
      growth, mitochondrial genome maintenance and mitochondrial protein synthesis in
      Saccharomyces cerevisiae.
AB  - BACKGROUND: The mitochondrial respiratory chain produces metabolic energy by
      oxidative phosphorylation. Biogenesis of the respiratory chain requires the
      coordinated expression of two genomes: the nuclear genome encoding the vast
      majority of mitochondrial proteins, and the mitochondrial genome encoding a
      handful of mitochondrial proteins. The understanding of the molecular processes
      contributing to respiratory chain assembly and maintenance requires the
      systematic identification and functional analysis of the genes involved. RESULTS:
      We pursued a systematic, genome-wide approach to define the sets of genes
      required for respiratory activity and maintenance and expression of the
      mitochondrial genome in yeast. By comparative gene deletion analysis we found an
      unexpected phenotypic plasticity among respiratory-deficient mutants, and we
      identified ten previously uncharacterized genes essential for respiratory growth
      (RRG1 through RRG10). Systematic functional analysis of 319 respiratory-deficient
      mutants revealed 16 genes essential for maintenance of the mitochondrial genome,
      88 genes required for mitochondrial protein translation, and 10 genes required
      for expression of specific mitochondrial gene products. A group of mutants
      acquiring irreversible damage compromising respiratory capacity includes strains
      defective in assembly of the cytochrome c oxidase that were found to be
      particularly sensitive to aging. CONCLUSIONS: These data advance the
      understanding of the molecular processes contributing to maintenance of the
      mitochondrial genome, mitochondrial protein translation, and assembly of the
      respiratory chain. They revealed a number of previously uncharacterized
      components, and provide a comprehensive picture of the molecular processes
      required for respiratory activity in a simple eukaryotic cell.

PMID- 19751519
TI  - Oral health related behaviors among adult Tanzanians: a national pathfinder
      survey.
AB  - BACKGROUND: The oral health education programs which have been organised and
      delivered in Tanzania were not based on a thorough understanding of behaviours
      which influence oral health. Therefore, evaluation of these programs became
      difficult. This study aimed at investigating the oral health related behaviours
      and their determinants among Tanzanian adults. METHODS: A national pathfinder
      cross sectional survey was conducted in 2006 involving 1759 respondents from the
      six geographic zones of mainland Tanzania. Frequency distributions, Chi square
      and multiple logistic regression analyses were performed using SPSS version 13.0.
      RESULTS: The rates of abstinence from alcohol for the past 30 days and life time
      smoking were 61.6% and 16.7% respectively, with males being more likely to smoke
      (OR 9.2, CI 6.3 -12.9, p < 0.001) and drink alcohol (OR 1.5, CI 1.2 -1.8, p <
      0.001). Multiple regression analysis revealed that; having dental pain (OR 0.7,
      CI 0.5-0.8; p < 0.001) and being minimally educated (OR 0.48, CI 0.4-0.6; p <
      0.001) reduced the likelihood of having a high sugar score. Whereas being male
      (OR 1.5, CI 1.2- 1.8; p < 0.001), urban (OR 1.9, CI 1.5 -2.3; p < 0.001), and
      young (OR 1.5, CI 1.2 -1.8; p < 0.001) increased the likelihood of having a high
      sugar score. Urban residents were less likely to take alcohol (OR 0.7, CI 0.6
      0.9; p < 0.01), or smoke cigarette (OR = 0.7, CI = 0.6-0.9); less likely to be
      those who do not use fruits (OR 0.3, CI 0.2-0.4; p < 0.001); dental clinic (OR
      0.5, CI 0.4-0.7; p < 0.001); factory made tooth brushes (OR 0.1, CI 0.08-0.17; p
      < 0.001) and toothpaste (OR 0.1, CI 0.1-0.2; p < 0.001) than their rural
      counterparts. More rural (13.2%) than urban (4.6%) residents used charcoal.
      CONCLUSION: The findings of this study demonstrated social demographic
      disparities in relation to oral health related behaviors, while dental pain was
      associated with low consumption of sugar and high likelihood to take alcohol.

PMID- 19751520
TI  - Amino acid residues 201-205 in C-terminal acidic tail region plays a crucial role
      in antibacterial activity of HMGB1.
AB  - BACKGROUND: Antibacterial activity is a novel function of high-mobility group box
      1 (HMGB1). However, the functional site for this new effect is presently unknown.
      METHODS AND RESULTS: In this study, recombinant human HMGB1 A box and B box
      (rHMGB1 A box, rHMGB1 B box), recombinant human HMGB1 (rHMGB1) and the truncated
      C-terminal acidic tail mutant (tHMGB1) were prepared by the prokaryotic
      expression system. The C-terminal acidic tail (C peptide) was synthesized, which
      was composed of 30 amino acid residues. Antibacterial assays showed that both the
      full length rHMGB1 and the synthetic C peptide alone could efficiently inhibit
      bacteria proliferation, but rHMGB1 A box and B box, and tHMGB1 lacking the C
      terminal acidic tail had no antibacterial function. These results suggest that C
      terminal acidic tail is the key region for the antibacterial activity of HMGB1.
      Furthermore, we prepared eleven different deleted mutants lacking several amino
      acid residues in C-terminal acidic tail of HMGB1. Antibacterial assays of these
      mutants demonstrate that the amino acid residues 201-205 in C-terminal acidic
      tail region is the core functional site for the antibacterial activity of the
      molecule. CONCLUSION: In sum, these results define the key region and the crucial
      site in HMGB1 for its antibacterial function, which is helpful to illustrating
      the antibacterial mechanisms of HMGB1.

PMID- 19751521
TI  - Inequities in maternal postnatal visits among public and private patients: 2004
      Pelotas cohort study.
AB  - BACKGROUND: The postnatal period is the ideal time to deliver interventions to
      improve the health of both the newborn and the mother. However, postnatal care
      shows low-level coverage in a large number of countries. The objectives of this
      study were to: 1) investigate inequities in maternal postnatal visits, 2) examine
      differences in postnatal care coverage between public and private providers and
      3) explore the relationship between the absence of maternal postnatal visits and
      exclusive breastfeeding, use of contraceptive methods and maternal smoking three
      months after birth. METHODS: In the calendar year of 2004 a birth cohort study
      was started in the city of Pelotas, Brazil. Mothers were interviewed soon after
      delivery and at three months after birth. The absence of postnatal visits was
      defined as having no consultations between the time of hospital discharge and the
      third month post-partum. Logistic regression analysis was used to estimate the
      association between absence of postnatal visits and type of insurance scheme
      adjusting for potential confounding factors. RESULTS: Poorer women, black/mixed,
      those with lower level of education, single mothers, adolescents, multiparae,
      smokers, women who delivered vaginally and those who were not assisted by a
      physician were less likely to attend postnatal care. Postnatal visits were also
      less frequent among women who relied in the public sector than among private
      patients (72.4% vs 96% among public and private patients, respectively, x2 p <
      0.001) and this difference was not explained either by maternal characteristics
      or by health care utilization patterns. Women who attended postnatal visits were
      more likely to exclusively breastfeed their infants, to use contraceptive methods
      and to be non-smokers three months after birth. CONCLUSION: Postpartum care is
      available for every woman free of charge in the Brazilian Publicly-funded health
      care system. However, low levels of postpartum care were seen in the study (77%).
      Efforts should be made to increase the percentage of women receiving postpartum
      care, particularly those in socially disadvantaged groups. This could include
      locally-adapted health education interventions that address women's beliefs and
      attitudes towards postpartum care. There is a need to monitor postpartum care and
      collected data should be used to guide policies for health care systems.

PMID- 19751522
TI  - malT knockout mutation invokes a stringent type gene-expression profile in
      Actinobacillus pleuropneumoniae in bronchoalveolar fluid.
AB  - BACKGROUND: Actinobacillus pleuropneumoniae causes contagious pleuropneumonia, an
      economically important disease of commercially reared pigs throughout the world.
      To cause this disease, A. pleuropneumoniae must rapidly overcome porcine
      pulmonary innate immune defenses. Since bronchoalveolar fluid (BALF) contains
      many of the innate immune and other components found in the lungs, we examined
      the gene expression of a virulent serovar 1 strain of A. pleuropneumoniae after
      exposure to concentrated BALF for 30 min. RESULTS: In reverse transcription PCR
      differential display (RT-PCR DD) experiments, A. pleuropneumoniae CM5 exposed to
      BALF up-regulated, among other genes, a gene predicted to encode LamB, an outer
      membrane transport protein of the maltose regulon. To determine the role of the
      lamB and other genes of the maltose regulon in the pathogenesis of A.
      pleuropneumoniae, knockout mutations were created in the lamB and malT genes, the
      latter being the positive transcriptional regulator of the maltose regulon.
      Relative to the lamB mutant and the wild type, the malT mutant had a significant
      (P < 0.05) decrease in growth rate and an increased sensitivity to fresh porcine
      serum and high concentrations (more than 0.5 M) of sodium chloride. In DNA
      microarray experiments, the BALF-exposed malT mutant exhibited a gene-expression
      profile resembling that of a stringent type gene-expression profile seen in
      bacteria facing amino acid or carbon starvation. Genes encoding proteins for
      protein synthesis, energy metabolism, and DNA replication were down-regulated,
      while genes involved in stringent response (e.g., relA), amino acid and
      nucleotide biosynthesis, biofilm formation, DNA transformation, and stress
      response were up-regulated. CONCLUSION: These results suggest that MalT may be
      involved in protection against some stressors and in the transport of one or more
      essential nutrients in BALF. Moreover, if MalT is directly or indirectly linked
      to the stringent response, an important global mechanism of bacterial persistence
      and virulence in many bacterial pathogens, it might play a role in A.
      pleuropneumoniae pathogenesis.

PMID- 19751523
TI  - Exploratory and inferential analysis of gene cluster neighborhood graphs.
AB  - BACKGROUND: Many different cluster methods are frequently used in gene expression
      data analysis to find groups of co-expressed genes. However, cluster algorithms
      with the ability to visualize the resulting clusters are usually preferred. The
      visualization of gene clusters gives practitioners an understanding of the
      cluster structure of their data and makes it easier to interpret the cluster
      results. RESULTS: In this paper recent extensions of R package gcExplorer are
      presented. gcExplorer is an interactive visualization toolbox for the
      investigation of the overall cluster structure as well as single clusters. The
      different visualization options including arbitrary node and panel functions are
      described in detail. Finally the toolbox can be used to investigate the quality
      of a given clustering graphically as well as theoretically by testing the
      association between a partition and a functional group under study. CONCLUSION:
      It is shown that gcExplorer is a very helpful tool for a general exploration of
      microarray experiments. The identification of potentially interesting gene
      candidates or functional groups is substantially accelerated and eased.
      Inferential analysis on a cluster solution is used to judge its ability to
      provide insight into the underlying mechanistic biology of the experiment.

PMID- 19751524
TI  - The relationship between the evolution of microRNA targets and the length of
      their UTRs.
AB  - BACKGROUND: MicroRNAs (miRNAs) are endogenous small RNA molecules that modulate
      the gene expression at the post-transcription levels in many eukaryotic cells.
      Their widespread and important role in animals is gauged by estimates that
      approximately 25% of all genes are miRNA targets. RESULTS: We perform a
      systematic investigation of the relationship between miRNA regulation and their
      targets' evolution in two mammals: human and mouse. We find genes with longer 3'
      UTRs are regulated by more distinct types of miRNAs. These genes correspondingly
      tend to have slower evolutionary rates at the protein level. Housekeeping genes
      are another class of genes that evolve slowly. However, they have a distinctly
      different type of regulation, with shorter 3'UTRs to avoid miRNA targeting.
      CONCLUSION: Our analysis suggests a two-way evolutionary mechanism for miRNA
      targets on the basis of their cellular roles and the length of their 3' UTRs.
      Functionally critical genes that are spatially or temporally expressed are
      stringently regulated by miRNAs. While housekeeping genes, however conserved, are
      selected to have shorter 3'UTRs to avoid miRNA regulation.

PMID- 19751525
TI  - First multi-locus sequence typing scheme for Arcobacter spp.
AB  - BACKGROUND: Arcobacter spp. are a common contaminant of food and water, and some
      species, primarily A. butzleri and A. cryaerophilus, have been isolated
      increasingly from human diarrheal stool samples. Here, we describe the first
      Arcobacter multilocus sequence typing (MLST) method for A. butzleri, A.
      cryaerophilus, A. skirrowii, A. cibarius and A. thereius. RESULTS: A sample set
      of 374 arcobacters, including 275 A. butzleri, 72 A. cryaerophilus, 15 A.
      skirrowii and 8 A. cibarius isolates from a wide variety of geographic locations
      and sources, was typed in this study. Additionally, this sample set contained
      four strains representing a new Arcobacter species, A. thereius. The seven loci
      used in the four-species Arcobacter MLST method are the same as those employed
      previously in C. jejuni, C. coli, C. helveticus and C. fetus (i.e. aspA,
      atpA(uncA), glnA, gltA, glyA, pgm and tkt). A large number of alleles were
      identified at each locus with the majority of isolates containing a unique
      sequence type. All Arcobacter isolates typed in this study contain two glyA
      genes, one linked to lysS (glyA1) and the other linked to ada (glyA2). glyA1 was
      incorporated into the Arcobacter MLST method while glyA2 was not because it did
      not increase substantially the level of discrimination. CONCLUSION: No
      association of MLST alleles or sequence types with host or geographical source
      was observed with this sample set. Nevertheless, the large number of identified
      alleles and sequence types indicate that this MLST method will prove useful in
      both Arcobacter strain discrimination and in epidemiological studies of sporadic
      Arcobacter-related gastroenteritis. A new Arcobacter MLST database was created
      http://pubmlst.org/arcobacter/; allele and ST data generated in this study were
      deposited in this database and are available online.

PMID- 19751526
TI  - Agreement between questionnaire and medical records on some health and
      socioeconomic problems among poisoning cases.
AB  - BACKGROUND: The main objective of the present study was to evaluate the agreement
      between questionnaire and medical records on some health and socioeconomic
      problems among poisoning cases. METHODS: Cross-sectional sample of 100 poisoning
      cases consecutively admitted to the Hospital Pulau Pinang, Malaysia during the
      period from September 2003 to February 2004 were studied. Data on health and
      socioeconomic problems were collected both by self-administered questionnaire and
      from medical records. Agreement between the two sets of data was assessed by
      calculating the concordance rate, Kappa (k) and PABAK. McNemar statistic was used
      to test differences between categories. RESULTS: Data collected by questionnaire
      and medical records showed excellent agreement on the "marital status"; good
      agreements on "chronic illness", "psychiatric illness", and "previous history of
      poisoning"; and fair agreements on "at least one health problem", and "boy-girl
      friends problem". PABAK values suggest better agreements' measures. CONCLUSION:
      There were excellent to good agreements between questionnaire and medical records
      on the marital status and most of the health problems and fair to poor agreements
      on the majority of socioeconomic problems. The implications of those findings
      were discussed.

PMID- 19751527
TI  - GP and nurses' perceptions of how after hours care for people receiving
      palliative care at home could be improved: a mixed methods study.
AB  - BACKGROUND: Primary health care providers play a dominant role in the provision
      of palliative care (PC) in Australia but many gaps in after hours service remain.
      In some rural areas only 19% of people receiving palliative care achieve their
      goal of dying at home. This study, which builds on an earlier qualitative phase
      of the project, investigates the gaps in care from the perspective of general
      practitioners (GPs) and PC nurses. METHODS: Questionnaires, developed from the
      outcomes of the earlier phase, and containing both structured and open ended
      questions, were distributed through Divisions of General Practice (1 urban, 1
      rural, 1 mixed) to GPs (n = 524) and through a special interest group to
      palliative care nurses (n = 122) in both rural and urban areas. RESULTS:
      Questionnaires were returned by 114 GPs (22%) and 52 nurses (43%). The majority
      of GPs were associated with a practice which provided some after hours services
      but PC was not a strong focus for most. This was reflected in low levels of PC
      training, limited awareness of the existence of after hours triage services in
      their area, and of the availability of Enhanced Primary Care (EPC) Medicare items
      for care planning for palliative patients. However, more than half of both nurses
      and GPs were aware of accessible PC resources.Factors such as poor communication
      and limited availability of after hours services were identified the as most
      likely to impact negatively on service provision. Strategies considered most
      likely to improve after hours services were individual patient protocols,
      palliative care trained respite carers and regular multidisciplinary meetings
      that included the GP. CONCLUSION: While some of the identified gaps can only be
      met by long term funding and policy change, educational tools for use in training
      programs in PC for health professionals, which focus on the utilisation of EPC
      Medicare items in palliative care planning, the development of advance care plans
      and good communication between members of multidisciplinary teams, which include
      the GP, may enhance after hours service provision for patients receiving
      palliative care at home. The role of locums in after PC is an area for further
      research.

PMID- 19751528
TI  - Information in small neuronal ensemble activity in the hippocampal CA1 during
      delayed non-matching to sample performance in rats.
AB  - BACKGROUND: The matrix-like organization of the hippocampus, with its several
      inputs and outputs, has given rise to several theories related to hippocampal
      information processing. Single-cell electrophysiological studies and studies of
      lesions or genetically altered animals using recognition memory tasks such as
      delayed non-matching-to-sample (DNMS) tasks support the theories. However, a
      complete understanding of hippocampal function necessitates knowledge of the
      encoding of information by multiple neurons in a single trial. The role of
      neuronal ensembles in the hippocampal CA1 for a DNMS task was assessed
      quantitatively in this study using multi-neuronal recordings and an artificial
      neural network classifier as a decoder. RESULTS: The activity of small neuronal
      ensembles (6-18 cells) over brief time intervals (2-50 ms) contains accurate
      information specifically related to the matching/non-matching of continuously
      presented stimuli (stimulus comparison). The accuracy of the combination of
      neurons pooled over all the ensembles was markedly lower than those of the
      ensembles over all examined time intervals. CONCLUSION: The results show that the
      spatiotemporal patterns of spiking activity among cells in the small neuronal
      ensemble contain much information that is specifically useful for the stimulus
      comparison. Small neuronal networks in the hippocampal CA1 might therefore act as
      a comparator during recognition memory tasks.

PMID- 19751529
TI  - A pre-S gene chip to detect pre-S deletions in hepatitis B virus large surface
      antigen as a predictive marker for hepatoma risk in chronic hepatitis B virus
      carriers.
AB  - BACKGROUND: Chronic hepatitis B virus (HBV) infection is an important cause of
      hepatocellular carcinoma (HCC) worldwide. The pre-S1 and -S2 mutant large HBV
      surface antigen (LHBS), in which the pre-S1 and -S2 regions of the LHBS gene are
      partially deleted, are highly associated with HBV-related HCC. METHODS: The pre-S
      region of the LHBS gene in two hundred and one HBV-positive serum samples was PCR
      amplified and sequenced. A pre-S oligonucleotide gene chip was developed to
      efficiently detect pre-S deletions in chronic HBV carriers. Twenty serum samples
      from chronic HBV carriers were analyzed using the chip. RESULTS: The pre-S
      deletion rates were relatively low (7%) in the sera of patients with acute HBV
      infection. They gradually increased in periods of persistent HBV infection: pre-S
      mutation rates were 37% in chronic HBV carriers, and as high as 60% in HCC
      patients. The Pre-S Gene Chip offers a highly sensitive and specific method for
      pre-S deletion detection and is less expensive and more efficient (turnaround
      time 3 days) than DNA sequencing analysis. CONCLUSION: The pre-S1/2 mutants may
      emerge during the long-term persistence of the HBV genome in carriers and
      facilitate HCC development. Combined detection of pre-S mutations, other markers
      of HBV replication, and viral titers, offers a reliable predictive method for HCC
      risks in chronic HBV carriers.

PMID- 19751530
TI  - Outer membrane vesicles of Helicobacter pylori TK1402 are involved in biofilm
      formation.
AB  - BACKGROUND: Helicobacter pylori forms biofilms on glass surfaces at the air
      liquid interface in in vitro batch cultures; however, biofilms of H. pylori have
      not been well characterized. In the present study, we analyzed the ability of H.
      pylori strains to form biofilms and characterized the underlying mechanisms of H.
      pylori biofilm formation. RESULTS: Strain TK1402 showed strong biofilm forming
      ability relative to the other strains in Brucella broth supplemented with 7% FCS.
      The strong biofilm forming ability of TK1402 is reflected the relative thickness
      of the biofilms. In addition, outer membrane vesicles (OMV) were detected within
      the matrix of only the TK1402 biofilms. Biofilm formation was strongly correlated
      with the production of OMV in this strain. We further observed that strain TK1402
      did not form thick biofilms in Brucella broth supplemented with 0.2% beta
      cyclodextrin. However, the addition of the OMV-fraction collected from TK1402
      could enhance biofilm formation. CONCLUSION: The results suggested that OMV
      produced from TK1402 play an important role in biofilm formation in strain
      TK1402.

PMID- 19751531
TI  - Sequenced BAC anchored reference genetic map that reconciles the ten individual
      chromosomes of Brassica rapa.
AB  - BACKGROUND: In view of the immense value of Brassica rapa in the fields of
      agriculture and molecular biology, the multinational Brassica rapa Genome
      Sequencing Project (BrGSP) was launched in 2003 by five countries. The developing
      BrGSP has valuable resources for the community, including a reference genetic map
      and seed BAC sequences. Although the initial B. rapa linkage map served as a
      reference for the BrGSP, there was ambiguity in reconciling the linkage groups
      with the ten chromosomes of B. rapa. Consequently, the BrGSP assigned each of the
      linkage groups to the project members as chromosome substitutes for sequencing.
      RESULTS: We identified simple sequence repeat (SSR) motifs in the B. rapa genome
      with the sequences of seed BACs used for the BrGSP. By testing 749 amplicons
      containing SSR motifs, we identified polymorphisms that enabled the anchoring of
      188 BACs onto the B. rapa reference linkage map consisting of 719 loci in the 10
      linkage groups with an average distance of 1.6 cM between adjacent loci. The
      anchored BAC sequences enabled the identification of 30 blocks of conserved
      synteny, totaling 534.9 cM in length, between the genomes of B. rapa and
      Arabidopsis thaliana. Most of these were consistent with previously reported
      duplication and rearrangement events that differentiate these genomes. However,
      we were able to identify the collinear regions for seven additional previously
      uncharacterized sections of the A genome. Integration of the linkage map with the
      B. rapa cytogenetic map was accomplished by FISH with probes representing 20 BAC
      clones, along with probes for rDNA and centromeric repeat sequences. This
      integration enabled unambiguous alignment and orientation of the maps
      representing the 10 B. rapa chromosomes. CONCLUSION: We developed a second
      generation reference linkage map for B. rapa, which was aligned unambiguously to
      the B. rapa cytogenetic map. Furthermore, using our data, we confirmed and
      extended the comparative genome analysis between B. rapa and A. thaliana. This
      work will serve as a basis for integrating the genetic, physical, and chromosome
      maps of the BrGSP, as well as for studies on polyploidization, speciation, and
      genome duplication in the genus Brassica.

PMID- 19751532
TI  - Sialylated glycans as receptor and inhibitor of enterovirus 71 infection to DLD-1
      intestinal cells.
AB  - BACKGROUND: Many viruses recognize specific sugar residues, particularly sulfated
      or sialylated glycans, as the infection receptors. A change of sialic acid (2-6)
      linked galactose (SA-alpha2,6Gal) to SA-alpha2,3Gal determines the receptor for
      avian flu infection. The receptor for enterovirus 71 (EV71) infection that
      frequently causes fatal encephalitis in Asian children remains unclear.
      Currently, there is no effective vaccine or anti-virus agent for EV71 infection.
      Using DLD-1 intestinal cells, this study investigated whether SA-linked glycan on
      DLD-1 intestinal cells was a receptor for EV71, and whether natural SA-linked
      sugars from human milk could block EV71 infection. RESULTS: EV71 specifically
      infected DLD-1 intestinal cells but not K562 myeloid cells. Depletion of O-linked
      glycans or glycolipids, but not N-linked glycans, significantly decreased EV71
      infection of DLD-1 cells. Pretreatment of DLD-1 cells with sialidase (10 mU, 2
      hours) significantly reduced 20-fold EV71 replication (p < 0.01). Taken together,
      these results suggest that SA-linked O-glycans and glycolipids, but not N
      glycans, on DLD-1 cells were responsible for EV71 infection. Purified SA
      alpha2,3Gal and SA-alpha2,6Gal from human milk significantly inhibited EV71
      infection of DLD-1 cells, indicating terminal SA-linked glycans could be
      receptors and inhibitors of EV71 infection. CONCLUSION: This is the first in the
      literature to demonstrate that EV71 uses SA-linked glycans as receptors for
      infection, and natural SA-linked glycans from human milk can protect intestinal
      cells from EV71 infection. Further studies will test how a SA-containing glycan
      can prevent EV71 in the future.

PMID- 19751533
TI  - Conserved repertoire of orthologous vomeronasal type 1 receptor genes in ruminant
      species.
AB  - BACKGROUND: In mammals, pheromones play an important role in social and innate
      reproductive behavior within species. In rodents, vomeronasal receptor type 1
      (V1R), which is specifically expressed in the vomeronasal organ, is thought to
      detect pheromones. The V1R gene repertoire differs dramatically between mammalian
      species, and the presence of species-specific V1R subfamilies in mouse and rat
      suggests that V1R plays a profound role in species-specific recognition of
      pheromones. In ruminants, however, the molecular mechanism(s) for pheromone
      perception is not well understood. Interestingly, goat male pheromone, which can
      induce out-of-season ovulation in anestrous females, causes the same pheromone
      response in sheep, and vice versa, suggesting that there may be mechanisms for
      detecting "inter-species" pheromones among ruminant species. RESULTS: We isolated
      23 goat and 21 sheep intact V1R genes based on sequence similarity with 32 cow
      V1R genes in the cow genome database. We found that all of the goat and sheep V1R
      genes have orthologs in their cross-species counterparts among these three
      ruminant species and that the sequence identity of V1R orthologous pairs among
      these ruminants is much higher than that of mouse-rat V1R orthologous pairs.
      Furthermore, all goat V1Rs examined thus far are expressed not only in the
      vomeronasal organ but also in the main olfactory epithelium. CONCLUSION: Our
      results suggest that, compared with rodents, the repertoire of orthologous V1R
      genes is remarkably conserved among the ruminants cow, sheep and goat. We predict
      that these orthologous V1Rs can detect the same or closely related chemical
      compound(s) within each orthologous set/pair. Furthermore, all identified goat
      V1Rs are expressed in the vomeronasal organ and the main olfactory epithelium,
      suggesting that V1R-mediated ligand information can be detected and processed by
      both the main and accessory olfactory systems. The fact that ruminant and rodent
      V1Rs have distinct features suggests that ruminant and rodent V1Rs have evolved
      distinct functions.

PMID- 19751534
TI  - Green tea (Camellia sinensis) catechins and vascular function.
AB  - The health benefits of green tea (Camellia sinensis) catechins are becoming
      increasingly recognised. Amongst the proposed benefits are the maintenance of
      endothelial function and vascular homeostasis and an associated reduction in
      atherogenesis and CVD risk. The mounting evidence for the influential effect of
      green tea catechins on vascular function from epidemiological, human intervention
      and animal studies is subject to review together with exploration of the
      potential mechanistic pathways involved. Epigallocatechin-3-gallate, one of the
      most abundant and widely studied catechin found in green tea, will be prominent
      in the present review. Since there is a substantial inconsistency in the
      published data with regards to the impact of green tea catechins on vascular
      function, evaluation and interpretation of the inter- and intra-study variability
      is included. In conclusion, a positive effect of green tea catechins on vascular
      function is becoming apparent. Further studies in animal and cell models using
      physiological concentrations of catechins and their metabolites are warranted in
      order to gain some insight into the physiology and molecular basis of the
      observed beneficial effects.

PMID- 19751535
TI  - Set up of a new in vitro model to study dietary fructans fermentation in formula
      fed babies.
AB  - A new in vitro fermentation model with immobilised infant faecal microbiota
      simulating the proximal colon of a formula-fed baby was developed and used to
      test the effects of known prebiotic fructans. Intestinal fermentation, based on a
      previously developed colonic fermentation model, using a new feeding medium
      simulating a formula-fed infant ileal chyme, was carried out for seventy-one
      consecutive days divided into four stabilisation periods intercalated with four
      prebiotic treatment periods. At the end of the first stabilisation period, total
      bacterial concentration in colonised beads and in faecal sample was similar,
      metabolite concentrations returned to stabilisation values after each treatment
      period. As expected, the four prebiotic treatments significantly increased the
      bifidobacterial populations, whereas they decreased bacteroides and clostridia.
      No difference was observed in the prebiotic effect of these substrates selected.
      The treatments significantly increased total production of SCFA and decreased
      ammonia compared to stabilisation periods. Long-term stability of the system
      together with the reproducibility of the known prebiotic effects highlights the
      potential of the present model to quantify and compare the effects of different
      substrates in a formula-fed infant microbiota within the same fermentation
      experiment.

PMID- 19751536
TI  - Antioxidant activity, bioactive polyphenols in Mexican goats' milk cheeses on
      summer grazing.
AB  - Two feeding systems trials were carried out to determine the antioxidant activity
      of soft goats' milk cheeses, and also to evaluate the presence of bioactive
      polyphenolic compounds. Two groups (A and B), each one with 20 (BW 50+/-5 kg)
      French Alpine goats were employed. All animals had between 70 to 80 milking days
      and were milked once a day. Group A included daily grazing on shruby rangeland
      vegetation, and group B was kept in full indoor confinement. Thirty kg of goats'
      milk from each group were collected; 15 kg from each were pasteurized and the
      remaining 15 kg were not pasteurized (raw), resulting in four treatments (two
      feeding system x two milk treatments). Soft goat's cheese antioxidant activity
      can be modified by the animals feeding system; grazing management represents a
      better option than indoor feeding to produce a healthy profile of bioactive
      compounds; providing an increase of total polyphenol, hydroxycinnamic acids and
      flavonoid concentrations. Pasteurization did have a significant effect on these
      metabolites, and diminished total polyphenol concentration. More research is
      needed to elucidate the potential of soft goat's cheese as a functional food.

PMID- 19751537
TI  - Identification of colonization factors of enterotoxigenic Escherichia coli with
      PCR-based technique.
AB  - Colonization factors (CFs) mediate attachment of enterotoxigenic Escherichia coli
      (ETEC) to the intestinal mucosa and induce protective immunity against ETEC
      diarrhoea. We designed CF-specific polymerase chain reaction (PCR) primers, and
      developed a simple PCR-based genotypic CF identification method. ETEC strains
      (n=17) isolated from patients with diarrhoea in Thailand were examined for
      genotypical identification of CFs of ETEC strains. Coli surface antigen 6 (CS6)
      was the most common CF (29%), followed by CS13 (12%), colonization factor antigen
      I (CFA/I), CS2 and CS3, and CS17/CS19 (6% each), while 41% of the strains were
      negative. This simple PCR method for the detection of CF genes is useful for
      surveillance of ETEC infections in diagnostic laboratories.

PMID- 19751538
TI  - Outbreak of giardiasis associated with a community drinking-water source.
AB  - Giardiasis is a common waterborne gastrointestinal illness. In 2007, a community
      giardiasis outbreak occurred in New Hampshire, USA. We conducted a cohort study
      to identify risk factors for giardiasis, and stool and environmental samples were
      analysed. Consuming tap water was significantly associated with illness (risk
      ratio 4.7, 95% confidence interval 1.5-14.4). Drinking-water samples were
      coliform-contaminated and a suspect Giardia cyst was identified in a home water
      filter. One well was coliform-contaminated, and testing indicated that it was
      potentially under the influence of surface water. The well was located 12.5 m
      from a Giardia-contaminated brook, although the genotype differed from clinical
      specimens. Local water regulations require well placement at least 15 m from
      surface water. This outbreak, which caused illness in 31 persons, represents the
      largest community drinking-water-associated giardiasis outbreak in the USA in 10
      years. Adherence to well placement regulations might have prevented this
      outbreak.

PMID- 19751539
TI  - A pilot study measuring the impact of yoga on the trait of mindfulness.
AB  - BACKGROUND: The current study examined whether yoga would increase levels of
      mindfulness in a healthy population. METHOD: Forty-six participants were randomly
      assigned to an 8-week yoga intervention group or a wait-list control group.
      Mindfulness was assessed pre and post yoga, using the Freiburg Mindfulness
      Inventory (FMI). RESULTS: Results indicate that the yoga group experienced a
      significant increase in Overall mindfulness, and in three mindfulness subscales;
      Attention to the present moment, Accepting and open attitudes toward experience,
      and Insightful understanding (p < .01). The control group experienced a
      significant increase in overall mindfulness (p < .02) and insightful
      understanding (p < .01). Findings suggest that a yoga intervention may be a
      viable method for increasing levels of trait mindfulness in a healthy population,
      potentially implicating yoga as a preventive method for the later development of
      negative emotional mood states (i.e. anxiety and depression). The control group
      also experienced moderate elevations of mindfulness at the second assessment.

PMID- 19751540
TI  - Separation of genetic influences on attention deficit hyperactivity disorder
      symptoms and reaction time performance from those on IQ.
AB  - BACKGROUND: Attention deficit hyperactivity disorder (ADHD) shows a strong
      phenotypic and genetic association with reaction time (RT) variability,
      considered to reflect lapses in attention. Yet we know little about whether this
      aetiological pathway is shared with other affected cognitive processes in ADHD,
      such as lower IQs or the generally slower responses (mean RTs). We aimed to
      address the question of whether a shared set of genes exist that influence RT
      variability, mean RT, IQ and ADHD symptom scores, or whether there is evidence of
      separate aetiological pathways. METHOD: Multivariate structural equation
      modelling on cognitive tasks data (providing RT data), IQ and ADHD ratings by
      parents and teachers collected on general population sample of 1314 twins, at
      ages 7-10 years. RESULTS: Multivariate structural equation models indicated that
      the shared genetic influences underlying both ADHD symptom scores and RT
      variability are also shared with those underlying mean RT, with both types of RT
      data largely indexing the same underlying liability. By contrast, the shared
      genetic influences on ADHD symptom scores and RT variability (or mean RT) are
      largely independent of the genetic influences that ADHD symptom scores share with
      IQ. CONCLUSIONS: The finding of unique aetiological pathways between IQ and RT
      data, but shared components between mean RT, RT variability and ADHD symptom
      scores, illustrates key influences in the genetic architecture of the cognitive
      and energetic processes that underlie the behavioural symptoms of ADHD. In
      addition, the multivariate genetic model fitting findings provide valuable
      information for future molecular genetic analyses.

PMID- 19751541
TI  - Sense of hyper-positive self, goal-attainment beliefs and coping strategies in
      bipolar I disorder.
AB  - BACKGROUND: There is some evidence that cognitive therapy (CT) is beneficial in
      reducing relapses in bipolar disorder. However, not all bipolar patients benefit
      from it. A previous study found that a group of non-responders to CT shared
      common characteristics: they value some of the high goal-attainment beliefs and
      characteristics associated with being in a state of mild hypomania - a high
      'sense of hyper-positive self' (SHPS). To promote of our understanding of this
      group of patients, the present study investigated the relationship between SHPS,
      preferred internal state, dysfunctional attitudes and coping with hypothetical
      manic prodromal scenarios. METHOD: Fifty-four bipolar I patients filled in self
      report questionnaires that assess preferred mood state, coping with scenarios,
      dysfunctional attitudes and SHPS. RESULTS: The Sense of Hyper-positive Self Scale
      Ideal score (SHPSS-Ideal) predicted patients' preferred internal state of mania.
      Coping with hypothetical scenarios was predicted by Dysfunctional Attitude Scale
      (DAS) goal-attainment scores: the higher the goal-attainment score, the higher
      the participant's tendency to identify with self-descriptors linked to hypomania
      and to engage in stimulating behaviours that may escalate the prodromal stage to
      mania. CONCLUSIONS: Clinicians should check and modify goal-attainment beliefs,
      particularly of those who exhibit features of SHPS. These patients' tendency to
      identify with hypomanic traits as self-descriptors should be dealt with by
      psychological techniques such as cognitive restructuring.

PMID- 19751542
TI  - Prognostic value of cognitive functioning for global functional recovery in first
      episode schizophrenia.
AB  - BACKGROUND: It has become widely accepted that cognitive deficits in
      schizophrenia are related to functional outcome. However, it remains to be seen
      whether these associations are relevant for predicting which cases will have a
      global functional recovery. In this study, we attempt to determine whether global
      functional recovery (integrating social and occupational outcomes) after first
      episode schizophrenia (FES) can be predicted by cognitive variables. METHOD: A
      total of 131 FES patients with functional deficits (n=97) and functional recovery
      (n=34) as determined at 1-year follow-up were examined. Neuropsychological,
      sociodemographic, pre-morbid and clinical data at baseline were analysed using
      independent groups comparisons and a logistic regression method. RESULTS:
      Sustained attention and negative symptoms emerged as significant predictors of
      good global functional outcome. Although the model revealed a high accuracy (91%)
      in the classification of patients with functional deficits, it was unacceptably
      low (26%) in the classification of patients with global functional recovery.
      CONCLUSIONS: The limitations found in the prediction of a favourable global
      functional outcome may well be an indication for a need to address the role of
      other factors not commonly included in longitudinal studies of long-term outcomes
      in schizophrenia.

PMID- 19751543
TI  - CRF receptor blockade prevents initiation and consolidation of stress effects on
      affect in the predator stress model of PTSD.
AB  - Post traumatic stress disorder (PTSD) is a chronic anxiety disorder initiated by
      an intensely threatening, traumatic event. There is a great need for more
      efficacious pharmacotherapy and preventive treatments for PTSD. In animals,
      corticotropin-releasing factor (CRF) and the CRF1 receptor play a critical role
      in behavioural and neuroendocrine responses to stress. We tested the hypothesis
      that CRF1 activation is required for initiation and consolidation of long-term
      effects of trauma on anxiety-like behaviour in the predator exposure (predator
      stress) model of PTSD. Male C57BL6 mice were treated with the selective CRF1
      antagonist CRA0450 (2, 20 mg/kg) 30 min before or just after predator stress.
      Long-term effects of stress on rodent anxiety were measured 7 d later using
      acoustic startle, elevated plus maze (EPM), light/dark box, and hole-board tests.
      Predator stress increased startle amplitude and delayed startle habituation,
      increased time in and decreased exits from the dark chamber in the light/dark box
      test, and decreased risk assessment in the EPM. CRF1 antagonism had limited
      effects on these behaviours in non-stressed controls, with the high dose
      decreasing risk assessment in the EPM. However, in stressed animals CRF1
      antagonism blocked initiation and consolidation of stressor effects on startle,
      and returned risk assessment to baseline levels in predator-stressed mice. These
      findings implicate CRF1 activation in initiation and post-trauma consolidation of
      predator stress effects on anxiety-like behaviour, specifically on increased
      arousal as measured by exaggerated startle behaviours. These data support further
      research of CRF1 antagonists as potential prophylactic treatments for PTSD.

PMID- 19751544
TI  - Antipsychotic drug-induced increases in ventral tegmental area dopamine neuron
      population activity via activation of the nucleus accumbens-ventral pallidum
      pathway.
AB  - Acute administration of antipsychotic drugs increases dopamine (DA) neuron
      activity and DA release via D2 receptor blockade. However, it is unclear whether
      the DA neuron activation produced by antipsychotic drugs is due to feedback from
      post-synaptic blockade or is due to an action on DA neuron autoreceptors. This
      was evaluated using two drugs: the first-generation antipsychotic drug
      haloperidol that has potent D2 blocking properties, and the second-generation
      drug sertindole, which is unique in that it is reported to fail to reverse the
      apomorphine-induced decrease in firing rate typically associated with DA neuron
      autoreceptor stimulation. Using single-unit extracellular recordings from ventral
      tegmental area (VTA) DA neurons in anaesthetized rats, both drugs were found to
      significantly increase the number of spontaneously active DA neurons (population
      activity). Apomorphine administered within 10 min either before or after
      sertindole reversed the sertindole-induced increase in population activity, but
      had no effect when administered 1 h after sertindole. Moreover, both sertindole-
      and haloperidol-induced increase in population activity was prevented when
      nucleus accumbens feedback was interrupted by local infusion of the GABAA
      antagonist bicuculline into the ventral pallidum. Taken together, these data
      suggest that antipsychotics increase DA neuron population activity via a common
      action on the nucleus accumbens-ventral pallidum-VTA feedback pathway and thus
      provide further elucidation on the mechanism by which antipsychotic drugs affect
      DA neuron activity. This provides an important insight into the relationship
      between altered DA neuron activity and potential antipsychotic efficacy.

PMID- 19751545
TI  - Blockade of [11C](+)-PHNO binding in human subjects by the dopamine D3 receptor
      antagonist ABT-925.
AB  - Dopamine D3 receptors are preferentially localized in the limbic system and
      midbrain, and thus may be involved in the pathophysiology of neuropsychiatry
      disorders. [11C](+)-PHNO is the first preferential D3 receptor radioligand in
      humans, yet there are no blockade studies with a D3 receptor antagonist in
      humans. This study characterized the blockade of [11C](+)-PHNO binding by ABT
      925, a D3 receptor antagonist, in healthy male subjects. Sixteen subjects
      underwent 2-3 positron emission tomography (PET) scans, at baseline and following
      one or two doses of ABT-925 ranging from 50 mg to 600 mg. Receptor occupancies
      were estimated for globus pallidus, substantia nigra, caudate, putamen, and
      ventral striatum. At the 600-mg dose (n=9), ABT-925 receptor occupancy (mean+/
      s.d.) was higher in substantia nigra (75+/-10%) and globus pallidus (64+/-22%)
      than in ventral striatum (44+/-17%), caudate (40+/-18%) and putamen (38+/-17%)
      (ANOVA: F4,140=15.02, p<0.001). The fractions of [11C](+)-PHNO binding
      attributable to D3 receptors in D3 receptor-rich regions were 100% (substantia
      nigra) and 90% (globus pallidus), and in D2 receptor-rich regions were 55%
      (caudate) and 53% (putamen). The ED50 of ABT-925 was 4.37 microg/ml across
      regions. Our results demonstrate that [11C](+)-PHNO binding can be blocked by a
      D3 receptor antagonist and confirm preclinical findings that [11C](+)-PHNO signal
      in the substantia nigra and globus pallidus is mainly reflective of its binding
      to D3 receptors. Thus, [11C](+)-PHNO seems a suitable PET radiotracer to estimate
      D3 receptor occupancy in humans.

PMID- 19751546
TI  - Neural substrates of self-regulatory control in children and adults with Tourette
      syndrome.
AB  - OBJECTIVE: To identify the neural substrate of self-regulatory control in
      children and adults with Tourette syndrome (TS). METHOD: We used event-related
      functional magnetic resonance imaging (fMRI) to study the neural correlates of
      cognitive self-regulation during the Simon task. Forty-two people from The Tic
      Disorder Specialty Clinic who met the Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition criteria for diagnosis with TS (24 children; 18 adults)
      were compared with 37 control subjects (19 children; 18 adults). Patients with TS
      were excluded from participation if they had any Axis I psychiatric disorder
      other than obsessive-compulsive disorder (OCD) or attention-deficit hyperactivity
      disorder (ADHD) prior to the onset of TS. Control participants were excluded if
      they reported a history of tic disorder, OCD, ADHD, or if they met diagnostic
      criteria for any Axis I disorder at the time of interview. RESULTS: We detected
      greater overall fMRI activation in adults than in children across both diagnostic
      groups, primarily in frontal and striatal regions. In both groups we also
      detected an age-related shift away from more general cortical activation toward a
      more specific reliance on frontostriatal activity, a developmental correlate that
      was exaggerated in the TS group despite behavioural performances similar to those
      of control subjects. Moreover, the severity of tics correlated positively with
      frontal activations across age groups. CONCLUSION: Frontostriatal circuits
      support cognitive and behavioural control. These circuits likely contribute both
      to optimal performance in this self-regulatory task and to the regulation of the
      severity of tics. Adults with persistent TS likely possess deficient activity in
      these circuits, attributable to either a failure of prefrontal plasticity or to
      disturbances in striatal functioning.

PMID- 19751547
TI  - Suicidal ideation: the role of economic and aboriginal cultural status after
      multivariate adjustment.
AB  - OBJECTIVE: To determine if Aboriginal (in this paper, First Nations and Metis
      people) cultural status is independently associated with lifetime suicidal
      ideation in the Saskatoon Health Region after controlling for other covariates,
      particularly income status. METHODS: Data collected by Statistics Canada in all 3
      cycles of the Canadian Community Health Survey (CCHS) were merged with identical
      questions asked in February 2007 by the Saskatoon Health Region. The health
      outcome was lifetime suicidal ideation. The risk indicators included
      demographics, socioeconomic status, cultural status, behaviours, life stress,
      health care use, and other health problems. RESULTS: Participants (n = 5948)
      completed the survey with a response rate of 81.1%. The prevalence of lifetime
      suicidal ideation was 11.9%. After stratification, it was found that high-income
      Aboriginal people have similar low levels of suicidal ideation, compared with
      high-income Caucasian people. The risk-hazard model demonstrated a larger
      independent effect of income status in explaining the association between
      Aboriginal cultural status and lifetime suicidal ideation, compared with the
      independent effect of age. After full multivariate adjustment, Aboriginal
      cultural status had a substantially reduced association with lifetime suicidal
      ideation. The odds of lifetime suicidal ideation for Aboriginal people reduced
      from 3.28 to 1.99 after multivariate adjustment for household income alone.
      CONCLUSION: The results of this study suggest reductions in lifetime suicidal
      ideation can be observed in Aboriginal people in Canada by adjusting levels of
      household income.

PMID- 19751548
TI  - Teen suicide information on the internet: a systematic analysis of quality.
AB  - OBJECTIVE: To synthesize the literature on youth suicide risk factors (RFs) and
      prevention strategies (PSs); evaluate quality of information regarding youth
      suicide RFs and PSs found on selected Canadian websites; determine if website
      source was related to evidence-based rating (EBR); and determine the association
      of website quality indicators with EBR. METHODS: Five systematic reviews of youth
      suicide research were analyzed to assemble the evidence base for RFs and PSs. The
      top 20 most commonly accessed youth suicide information websites were analyzed
      for quality indicators and EBR. Univariate logistic regression was conducted to
      determine if quality indicators predicted statements supported by evidence
      (SSEs). Multivariate analysis was used to calculate adjusted odds ratios for SSEs
      and quality indicators. RESULTS: Only 44.2% of statements were SSEs. The 10 most
      highly ranked websites contained almost 80% of the total statements analyzed, and
      one-half had a negative EBR. Compared with government websites, nonprofit
      organization websites were more likely (OR 1.45, 95% CI 0.66 to 3.18), and
      personal and media websites were less likely (OR 0.62, 95% CI 0.26 to 1.47), to
      have a positive EBR. Crediting of an author (AOR 2.65, 95% CI 1.34 to 5.28), and
      recommendation to consult a health professional (AOR 2.08, 95% CI 1.18 to 3.68),
      increased the odds of SSEs. CONCLUSIONS: Fundamental to addressing youth suicide
      is the availability of high-quality, evidence-based information accessible to the
      public, health providers, and policy-makers. Many websites, including those
      sponsored by the federal government and national organizations, need to improve
      the evidence-based quality of the information provided.

PMID- 19751549
TI  - [Nature and severity of oppositional defiant disorder and conduct disorder as
      they occur together or separately in children].
AB  - OBJECTIVE: Co-occurring oppositional defiant disorder and conduct disorder
      symptoms are particularly common, which could be related to the greater severity
      (number and nature of symptoms) of each disorder. Our study aims to determine if
      oppositional defiant disorder and conduct disorder symptoms vary when they occur
      together or separately in children. METHOD: Our study was conducted with 406
      children (aged 6 to 13 years) divided in 4 groups (oppositional disorder only,
      conduct disorder only, oppositional disorder and conduct disorder, control) with
      no age or sex difference. Structured diagnostic interviews conducted with one
      parent and each child separately led to assessing the average number of symptoms
      for each disorder as well as the onset frequency of each symptom. RESULTS: When
      occurring together, oppositional disorder and conduct disorder appear more severe
      than when they occur separately, considering the number and nature of symptoms
      shown. Further, children with an oppositional disorder only or a conduct disorder
      only also have more frequent symptoms of the other disorder, compared with
      children in the control group. CONCLUSION: These results suggest taking into
      account, at the time of assessment and potential intervention, the presence of
      both disorders.

PMID- 19751550
TI  - Managing depression during hepatitis C treatment.
AB  - OBJECTIVE: The prevalence of hepatitis C virus (HCV) infection in Canada is
      estimated to be 1% and expected to increase during the next decade. Mental
      illness, particularly depression, is common among HCV-infected patients and
      remains an obstacle to interferon-alpha (IFN-alpha) treatment. We summarize the
      risk factors for interferon-alpha-induced major depressive disorder (IFN-alpha
      MDD) in HCV patients and the evidence for antidepressant prophylaxis and
      symptomatic antidepressant treatment of depression. METHODS: We searched MEDLINE,
      EMBASE, and CINAHL for randomized controlled or quasi-experimental trials
      evaluating antidepressant prophylactic and symptomatic treatment approaches for
      depression emerging during IFN-alpha treatment. Manual searches of references
      listed in review articles, case series, and anecdotal reports supplemented our
      literature search. RESULTS: A total of 9 trials involving prophylactic and
      symptomatic treatment approaches for IFN-alpha-MDD are summarized in our review.
      Antidepressant pretreatment is beneficial for patients with elevated baseline
      depressive symptoms and a preexisting history of IFN-alpha-MDD. Although limited
      evidence exists for several antidepressant agents, much of the evidence suggests
      that selective serotonin reuptake inhibitors (SSRIs) are safe and efficacious in
      treating depressive symptoms secondary to IFN-alpha therapy. CONCLUSION: Both
      antidepressant pretreatment and symptomatic treatment are viable strategies for
      treating IFN-alpha-MDD. Improved treatment outcomes and early identification of
      depression during HCV treatment can be achieved using an integrated medical and
      mental health treatment approach.

PMID- 19751551
TI  - Three-year outcome of treatment in an early psychosis program.
AB  - OBJECTIVE: Studies defining the course and outcome of people experiencing their
      first episode psychosis (FEP) generally report an improvement in symptoms and
      functioning. Little is known about the follow-up arrangements offered to patients
      when their time in a FEP comes to an end. METHOD: Our study focuses on a sample
      of FEP patients (n = 292) who were followed for up to 3 years in a multi-element
      specialized FEP service. RESULTS: Improvement in positive symptoms and social
      functioning, but not negative symptoms, was observed in this sample both for
      people who completed 3 years in the program and for those who left early. About
      40% were referred to specialized mental health services, whereas 24% were
      followed by their family physician. Patients who were followed by family
      physicians had decreased symptoms and improved functioning. CONCLUSION: Most
      patients treated in an early psychosis program will need follow-up, the largest
      group will require specialized mental health services in the community, but a
      significant group can be followed by family physicians.

PMID- 19751552
TI  - Prevalence of childhood sexual abuse and timing of disclosure in a representative
      sample of adults from Quebec.
AB  - OBJECTIVE: Our study sought to explore patterns of disclosure of child sexual
      abuse (CSA) in a sample of adult men and women. METHOD: A telephone survey
      conducted with a representative sample of adults (n = 804) from Quebec assessed
      the prevalence of CSA and disclosure patterns. Analyses were carried out to
      determine whether disclosure groups differed in terms of psychological distress
      and symptoms of posttraumatic stress, and a logistic regression was used to
      examine factors associated with prompt disclosure. RESULTS: Prevalence of CSA was
      22.1% for women and 9.7% for men. About 1 survivor out of 5 had never disclosed
      the abuse, with men more likely not to have told anyone, than women. Only 21.2%
      of adults reported prompt disclosure (within a month of the first abusive event),
      while 57.5% delayed disclosure (more than 5 years after the first episode). CSA
      victims who never disclosed the abuse and those who delayed disclosure were more
      likely to obtain scores of psychological distress and posttraumatic stress
      achieving clinical levels, compared with adults without a history of CSA. In the
      multivariate analysis, experiencing CSA involving a perpetrator outside the
      immediate family and being female were factors independently associated with
      prompt disclosure. CONCLUSION: A significant number of adult women and men
      reported experiencing CSA, and most victims attested to either not disclosing or
      significantly delaying abuse disclosure.

PMID- 19751553
TI  - Are randomized controlled trials relevant to clinical practice?

PMID- 19751556
TI  - [Guidelines for prevention of deep venous thrombosis in intensive care unit
      patients].

PMID- 19751555
TI  - [More attentions should be paid to deep venous thrombosis of intensive care unit
      patients].

PMID- 19751557
TI  - [Influences of the phosphorylation of p38 mitogen activated protein kinase on
      gene expression of tumor necrosis factor-alpha in multiple organ dysfunction
      syndrome in pigs].
AB  - OBJECTIVE: To investigate that the phosphorylation of the p38 mitogen activated
      protein kinase (p38MAPK) influences gene expression of tumor necrosis factor
      alpha (TNF-alpha) in multiple organ dysfunction syndrome (MODS) in pigs. METHODS:
      Thirty pigs were divided into MODS group and control group, and an animal model
      of MODS of "two-hit" injury, including hemorrhagic shock and endotoxemia, was
      reproduced. The content of p38MAPK's phosphorylation was assessed with Western
      blotting. TNF-alpha mRNA in peripheral blood monocytes was assayed with real time
      polymerase chain reaction (RT-PCR). TNF-alpha was monitored in the peripheral
      blood plasma with enzyme linked immunosorbent assay (ELISA). RESULTS:
      Phosphorylation of p38MAPK was obviously increased in extent, which enhanced gene
      expression of TNF-alpha and then secretion of TNF-alpha by the peripheral blood
      mononuclear cell in MODS, and the differences were statistically significant
      compared with that of control group (P<0.05 or P<0.01). CONCLUSION: p38MAPK's
      phosphorylation is important in pathogenesis of MODS, and phosphorylation of
      p38MAPK can enhance TNF-alpha mRNA transcription and secretion of TNF-alpha from
      peripheral blood mononuclear cells, which is the mechanism of increased TNF-alpha
      in MODS.

PMID- 19751558
TI  - [The design of stretcher integrated first-aid system].
AB  - OBJECTIVE: To satisfy the requirements of pre-hospital and first aid at scene for
      critical patient, rapid transportation, and nonstop treatment in hospital, this
      paper describes a design of a stretcher integrated first-aid system (SIFAS),
      which can provide seamless link between pre-hospital and in-hospital first aid.
      METHODS: With the requirements of integration and informationization, related
      functional modules of the former invented SIFAS were redesigned with principle of
      miniaturization. Adhering to the principle of best man-machine performance,
      systemic structural characteristic was studied. Aiming at achieving the best
      maneuverability but with lightest weight, the materials and processing technology
      of the framework were modified and improved. RESULTS: The SIFAS designed
      possessed good flexibility, it could be carried on pushed, and it could be
      attached to many carriers, with shortened time, and continuous first aid could be
      realized, and waiting time for first aid was greatly reduced. CONCLUSION: The
      SIFAS provides a possibility for establishing a emergency green path for pre
      hospital and in-hospital first aid, and it improves emergency of the patient and
      quick response of relevant medical institutions.

PMID- 19751559
TI  - [The preemptive treatment of invasive Candida infection with reference of
      corrected colonization index in critically ill patients: a multicenter,
      prospective, randomized controlled clinical study].
AB  - OBJECTIVE: To evaluate preemptive treatment for invasive Candida infection (ICI)
      with reference of corrected colonization index (CCI) in critically ill patients
      with high risk factors of Candida infection, and to collect the epidemiology data
      of Candida infection. METHODS: One hundred and ten critically ill patients with
      acute physiology and chronic health evaluation II (APACHE II) score>10 were
      selected from intensive care units (ICUs) of 5 grade III class A hospitals in
      Tianjin from October 1st 2008 to April 30th 2009, and they were randomly divided
      into two groups: CCI group and control group (55 cases in each group). CCI was
      monitored in all patients. In control group the responsible intensivists ordered
      the treatment according to their own experience, and in CCI group, when the
      patient's CCI> or =0.4 and with evidence of sepsis, the patients were given anti
      Candida immediately. When CCI<0.4, anti-Candida treatment was not given. But when
      the patients' condition became worse or unstable, complementary anti-Candida
      treatment was given. RESULTS: There were no significant differences in general
      data, treatment of diseases of the patients, APACHE II scores, incidence of
      sepsis and length of ICU stay (LOS) between two groups ( all P>0.05 ). There were
      50 patients and 48 patients developing sepsis in control group and CCI group,
      respectively. In CCI group, the time between the onset of sepsis to beginning of
      anti-Candida treatment was significantly shorter than the control group [(0.94+/
      0.67) days vs. (3.75+/-3.62) days, P<0.05]. In the group of CCI> or =0.4 (57
      patients) the LOS [(15.34+/-6.63) days] and the incidence of failure in
      establishing enteral nutrition (64.9%) were significantly higher than that of the
      group of CCI<0.4 [53 patients, (7.24+/-3.75) days, 43.4%, both P<0.05]. There was
      no significant difference in APACHE II scores, incidence of mechanical
      ventilation and blood purification between two groups ( all P>0.05 ). Analysis of
      575 strains of Candida colonized in 110 patients, revealed that C. albicans
      ranked first (59.3%), C. tropicalis ranked second (10.8%), followed by C.
      glabrata, Cryptococcus and C. krusei. CONCLUSION: Application of CCI may enhance
      the accuracy of timely preemptive treatment for ICI, and facilitate the
      collection of epidemiological data of Candida in critically ill patients.

PMID- 19751560
TI  - [The effect of low-dose hydrocortisone on requirement of norepinephrine and
      lactate clearance in patients with refractory septic shock].
AB  - OBJECTIVE: To observe the effect of low-dose hydrocortisone on the requirement of
      norepinephrine and lactate clearance in patients with refractory septic shock,
      and to investigate the effect of stress dose corticosteroids in reversing septic
      shock and improving tissue oxygen supply. METHODS: Seventy-seven septic shock
      patients with hypotension refractory to fluids and administration of
      norepinephrine were randomly divided into control and treatment groups. In
      treatment group intravenous injection of low-dose hydrocortisone was given on top
      of the treatment given in control group for 14 days. The mean arterial pressure
      (MAP), lactate clearance and the data of norepinephrine use were compared between
      two groups during the course of treatment. RESULTS: The number of patients
      requiring norepinephrine was significantly lower and the MAP was significantly
      higher in 24 hours, 7 days, 14 days than those at the beginning of treatment in
      both groups (all P<0.01). Compare to the control group, the course of using
      norepinephrine was shorter and the number of using norepinephrine was smaller in
      7 days in treatment group (both P<0.05 ); the MAP and lactate clearance were
      higher in 24 hours and 7 days in treatment group (P<0.05 or P<0.01). But there
      were no differences in mortality and the length of stay in intensive care unit
      (ICU). CONCLUSION: For the patients with septic shock with refractory
      hypotension, low-dose hydrocortisone can decrease the time course and dosage of
      vasopressors, improve tissue oxygen supply, thus can reverse septic shock more
      rapidly.

PMID- 19751561
TI  - [Combined effect of high mobile group box-1 protein and lipopolysaccharide on
      release of cytokines from human HepG2 cells].
AB  - OBJECTIVE: To study the effects of high mobile group box-1 protein (HMGB1) and
      lipopolysaccharide (LPS) singly or in combination on release of cytokines from
      human liver carcinoma cell line (HepG2). METHODS: HepG2 cells were cultured, and
      purified HMGB1 protein was prepared by chromatography on Ni(2+)-NTA Sepharose
      column under natural conditions with recombinant expression plasmid pET14b-HMGB1.
      Different concentrations of HMGB1 (0, 0.01, 0.1, 1, 10 mg/L) and LPS (0, 0.1, 1,
      10, 100 mg/L) were added into the cultured cells for 24 hours, respectively. Then
      the supernatant were collected to detect the levels of granulocyte/macrophage
      colony stimulating factor (GM-CSF), interferon-gamma (IFN-gamma), tumor necrosis
      factor-alpha (TNF-alpha), and interleukin-1 beta (IL-1 beta), IL-2, IL-4, IL-6,
      IL-8, IL-10, and IL-12 by using LiquiChip system. Lastly, HepG2 cells were co
      stimulated with 10 mg/L LPS and 1 mg/L HMGB1 for 24 hours. The supernatant were
      collected to determine the levels of above ten of cytokines . RESULTS: The
      expression and release of IL-6 and IL-8 increased from HepG2 cells after being
      stimulated by LPS in a dose-dependent manner, but there were no changes in other
      eight kinds of cytokines (P<0.05 or P<0.01). Low concentration of HMGB1 could up
      regulate the expression of IL-6 and IL-8 in HepG2 cells (both P<0.01). But the
      extent of induction decreased with higher concentration of HMGB1. Similar to LPS,
      there was no effect of HMGB1 on the expression of other eight kinds of cytokines
      from cultured HepG2 cells. Furthermore, high concentration of HMGB1 could
      obviously inhibit the upregulation of IL-6 and IL-8 by high concentration of LPS
      when the HepG2 cells were co-stimulated with LPS and HMGB1 (both P<0.01).
      CONCLUSION: HepG2 cells could only express and release a few kinds of cytokines
      when the cells were stimulated with pro-inflammatory agents, such as LPS or
      HMGB1. Two kinds of cytokines, IL-6 and IL-8 could be up-regulated by LPS and low
      concentration of HMGB1, and HMGB1 acted as an inhibitor of LPS to down-regulate
      the expression and release of IL-6 and IL-8 from HepG2 cells.

PMID- 19751562
TI  - [Logistic regression analysis of the risk factors of patients with sepsis in
      intensive care unit].
AB  - OBJECTIVE: To investigate the correlation of the data of patients with sepsis in
      intensive care unit (ICU) and their prognosis. METHODS: Clinical data of 450
      cases with sepsis in ICU from January 2004 to December 2008 were retrospectively
      studied. Twenty-four possible prognostic factors including clinical, chemical
      examinations and scores contributing to the survival of these patients were
      analyzed with univariate and multivariate logistic regression analysis. RESULTS:
      Univariate logistic regression analysis: eight factors were non-risk factors for
      sepsis, including days of hospitalization [odds ratio (OR)=0.951, P<0.001],
      Glasgow coma score (GCS, OR=0.858 , P<0.001), mean arterial pressure (OR=0.991,
      P=0.041), platelet count (OR=0.997, P<0.001), total protein (OR=0.975,P=0.003),
      albumin (OR=0.955, P<0.001), arterial pH (OR=0.077,P=0.001), arterial oxygen
      pressure (OR=0.996, P=0.014). The risk factors for sepsis included acute
      physiology and chronic health evaluation II (APACHE II) score (OR=1.115,
      P<0.001), body temperature (OR=1.215, P=0.041), prothrombin time (OR=1.057,
      P=0.007), aspartate aminotransferase (OR=1.001, P=0.011), serum creatinine
      (OR=1.002, P=0.002), blood potassium level (OR=1.391, P=0.003), blood glucose
      (OR=1.051, P=0.002), and C-reactive protein (OR=1.245, P=0.001). Multivariate
      logistic regression analysis showed that risk factors of sepsis included APACHE
      II score (OR=1.094, P<0.001), days of hospitalization (OR=0.946, P<0.001),
      platelet count (OR=0.976, P=0.004), and albumin level (OR=0.957, P=0.017).
      CONCLUSION: APACHE II score, days of hospitalization, platelet count and albumin
      could predict the prognosis of sepsis.

PMID- 19751563
TI  - [The role of interferon-gamma in prevention of hydrogen peroxide-induced
      oxidative injury to vascular endothelium].
AB  - OBJECTIVE: To observe the protective effects of interferon-gamma (IFN-gamma) on
      hydrogen peroxide (H(2)O(2))-induced oxidative injury to vascular endothelial
      cell (VEC), and to explore the role of 26S proteasome protection against IFN
      gamma-induced endothelial oxidative injury. METHODS: A H(2)O(2)-induced VEC
      oxidative injury to cell and isolated organ models were reproduced in the current
      study. The VEC oxidative damage in cellular level was evaluated by the contents
      of lactate dehydrogenase (LDH) and malondialdehyde (MDA) in culture medium, and
      the degree of oxidative injury of VEC in isolated organ level was evaluated by
      acetylcholine (Ach)-induced endothelium- dependent vascular relaxation. RESULTS:
      H(2)O(2) triggered the oxidative injury in cultured VEC in a dose- and time
      dependent manner, characterized by an increased contents of LDH and MDA in
      culture medium (P<0.05 or P<0.01). The Ach-induced endothelium- dependent
      vascular relaxation was decreased, and as shown by a decrease in 10(-5) mol/L Ach
      induced maximum reaction of relaxation of vasculature from (95.82+/-9.25)% to
      (12.61+/-2.96)% (P<0.01). The damage to VEC induced by H(2)O(2) was diminished
      significantly after incubation with IFN-gamma (20 microg/L) for 48 hours,
      characterized by a decreased production of LDH and MDA (both P<0.05) and
      restoration of endothelium- dependent vasodilation, and Ach-induced maximum
      reaction of vascular relaxation was increased to (72.68+/-18.82)% (P<0.01). 26S
      proteasome inhibitor lactacystin could partly antagonize the protective effects
      of IFN-gamma on H(2)O(2)-induced oxidative injury. CONCLUSION: IFN-gamma
      possesses protective effects on H(2)O(2)-induced oxidative injury to vascular
      endothelium, and its mechanism is at least partly related with 26S proteasome.

PMID- 19751564
TI  - [The effects of dopamine on pulmonary artery pressure in dogs with endotoxic
      shock].
AB  - OBJECTIVE: To evaluate the values of dopamine in treating endotoxic shock by
      observing the changes in the pulmonary artery pressure (PAP) during the
      treatment. METHODS: Twenty healthy dogs were randomly divided into four groups
      with 5 in each group. Endotoxic model was reproduced by injecting
      lipopolysaccharides (LPS) 1 mg/kg intravenously. Two hours later, normal saline
      (NS) 5 ml/h was intravenously given in model group, or dopamine 5, 10, 20
      microg*kg(-1)*min(-1) was given in D5 group, D10 group, D20 group intravenously.
      Femoral artery pressure, femoral vein pressure and PAP were measured, and mean
      arterial pressure (MAP) and mean pulmonary artery pressure (MPAP) were recorded
      at 0, 5, 10, 30, 60, 120 minutes after infusion of NS or dopamine. RESULTS:
      Compared with the model group, all different concentrations of dopamine could
      elevate MAP, MPAP (P<0.05 or P<0.01). Compared with D5 group, the percentage of
      elevation of MAP of D10 group and D20 group was greater, and the percentage of
      elevation of MPAP of D20 group was greater than that in D5 group and D10 group
      (P<0.05 or P<0.01). The ratio of MAP/MPAP in each dopamine group was higher than
      that of model group, and the increase was more marked in the groups of higher
      concentrations (all P<0.05). CONCLUSION: MAP of endotoxic dog lowered obviously,
      while there was little change in PAP. After infusion of dopamine intravenously,
      both MAP and PAP are elevated. The increase in resistance of pulmonary
      microcirculation is the main reason for the elevation of PAP.

PMID- 19751565
TI  - [The expression of cholecystokinin-octapeptide receptor in vascular endothelial
      cells induced by lipopolysaccharide].
AB  - OBJECTIVE: To investigate the expression of cholecystokinin-octapeptide receptor
      (CCK-R) mRNA, and observe the effect of lipopolysaccharide (LPS) on CCK-AR mRNA
      and CCK-BR mRNA expression in ECV-304. METHODS: The human umbilical vein
      endothelial cell line ECV-304 was cultured and treated with LPS in dosage of
      0.01, 0.1, 1, 10 mg/L for 2 hours, or treated with LPS in dosage of 1 mg/L for
      0.5, 2, 6, 12 hours. Reverse transcription-polymerase chain reaction (RT-PCR) was
      employed to examine the expression of CCK-AR mRNA and CCK-BR mRNA in ECV-304, and
      to analyse the sequences of the amplification products. RESULTS: Compared with
      control group, the expression of CCK-AR mRNA and CCK-BR mRNA was significantly
      upregulated in a dose-dependence manner after incubated with 0.01, 0.1 and 1 mg/L
      LPS for 2 hours (all P<0.05). However, the expression of CCK-AR mRNA showed no
      significant increase,while that of CCK-BR mRNA was increased, after being
      incubated with 0.01 mg/L LPS. The expressions of CCK-AR mRNA and CCK-BR mRNA in
      the 10 mg/L LPS group showed no significant difference compared with 1 mg/L LPS
      group (both P>0.05). The expression of CCK-AR mRNA and CCK-BR mRNA was
      significantly upregulated in a time-dependence manner after incubated with 1 mg/L
      LPS from 0.5 hour to 2 hours compared with control group (all P<0.05). After
      incubated with 1 mg/L LPS for 6 hours, the expression of CCK-AR mRNA and CCK-BR
      mRNA was significantly decreased compared with 2-hour group, but was still higher
      than that of control group (both P<0.05). Its expression was decreased further
      after being incubated with 1 mg/L LPS for 12 hours compared with the 6 hours
      group (both P<0.05), but showed no significant difference compared with the
      control group (both P>0.05). CONCLUSION: Both CCK-AR mRNA and CCK-BR mRNA are
      expressed in ECV-304. LPS can up-regulate the expression of CCK-AR mRNA and CCK
      BR mRNA.

PMID- 19751566
TI  - [The protective effects of carbachol on visceral ischemia-induced lipid
      peroxidation injury in rats with sepsis].
AB  - OBJECTIVE: To investigate the effect of carbachol (CAR) on visceral perfusion and
      lipid oxidation injury in rats with sepsis. METHODS: Sixty-four Sprague-Dawley
      (SD) rats received cecal ligation and puncture (CLP) surgery, and they were
      divided randomly into two groups: septic model group (CLP group, n=32) and septic
      model with CAR-treatment group (CAR group, n=32). CAR (10 microg/kg, CAR group)
      or normal saline (CLP group) was immediately injected into penial vein. Sixteen
      animals in each group were used to observe the mortality rates 12 hours and 24
      hours after CLP, and the remaining rats for measurement of variables of blood and
      tissue. At the 18 hours after CLP, the mean arterial pressure (MAP), the blood
      flow (BF) of liver, kidney and jejunum, the plasma levels of alanine
      aminotransferase (ALT) and creatinine (Cr) were measured. Animals were sacrificed
      after the aforementioned determinations, and specimens of liver, kidney and
      jejunum were harvested for evaluation of malondialdehyde (MDA), xanthine oxidase
      (XOD), and assessment of tissue water content (ratio of dry to wet weight) of
      those organs . The activity of diamine oxidase (DAO) in jejunal tissue was
      detected. RESULTS: The mortality rates of 12 hours and 24 hours of CAR group were
      25.0% (4/16)and 50.0% (8/16) respectively, all significantly lower than those of
      CLP group [37.5% (6/16) and 75%(12/16), both P<0.05]. CAR treatment did not
      result in significant statistical difference in the levels of MAP compared with
      CLP group at 18 hours after CLP (P>0.05), but led to significant increases in BF
      of CAR group in liver, kidney and jejunum compared with those of CLP group (all
      P<0.05). The levels of XOD and MDA, as well as the tissue water content were
      significantly lower in CAR group than CLP group in kidney and jejunum (all
      P<0.05). The parameters of organ function were significantly different in CAR
      group compared with CLP group [ALT: (64.3+/- 8.3) U/L vs. (81.5+/-7.9) U/L, Cr:
      (96.4+/-7.0) micromol/L vs. (117.1+/-6.7) micromol/L, DAO: (0.20+/- 0.04) U/L vs.
      (0.12+/-0.03) U/L, all P<0.05]. CONCLUSION: The results indicate that CAR
      promotes visceral perfusion, inhibits lipid peroxidation production and
      alleviates visceral edema and dysfunction in rats with sepsis.

PMID- 19751567
TI  - [The questionnaire survey of present status of intensive care units in Shandong
      Province].

PMID- 19751568
TI  - [The value of immature granulocyte count in the diagnosis of systemic
      inflammatory response syndrome].

PMID- 19751569
TI  - [Influence of ulinastatin on expression of Toll-like receptor 4 on peripheral
      blood mononuclear cells in patients with sepsis].

PMID- 19751570
TI  - [Effect of Ulinastatin on circulatory function restoration in patients with acute
      myocardial infarction in cardiogenic shock].

PMID- 19751571
TI  - [Effects of Xuebijing injection on levels of tissue factor-bearing microparticles
      in peripheral blood in septic rats].

PMID- 19751572
TI  - [The relationship between damage associated molecular patterns, pathogen
      associated molecular patterns, alarmins and inflammatory response].

PMID- 19751573
TI  - [The mechanism of counter-modulatory effect of migration inhibitory factor on
      anti-inflammatory action of glucocorticoids].

PMID- 19751574
TI  - [Inflammation, endothelium, coagulation in sepsis].

PMID- 19751575
TI  - Reemerging rabies and lack of systemic surveillance in People's Republic of
      China.
AB  - Rabies is a reemerging disease in China. The high incidence of rabies leads to
      numerous concerns: a potential carrier-dog phenomenon, undocumented transmission
      of rabies virus from wildlife to dogs, counterfeit vaccines, vaccine mismatching,
      and seroconversion testing in patients after their completion of postexposure
      prophylaxis (PEP). These concerns are all scientifically arguable given a modern
      understanding of rabies. Rabies reemerges periodically in China because of high
      dog population density and low vaccination coverage in dogs. Mass vaccination
      campaigns rather than depopulation of dogs should be a long-term goal for rabies
      control. Seroconversion testing after vaccination is not necessary in either
      humans or animals. Human PEP should be initiated on the basis of diagnosis of
      biting animals. Reliable national systemic surveillance of rabies-related human
      deaths and of animal rabies prevalence is urgently needed. A laboratory diagnosis
      based epidemiologic surveillance system can provide substantial information about
      disease transmission and effective prevention strategies.

PMID- 19751576
TI  - Use of revised International Health Regulations during influenza A (H1N1)
      epidemic, 2009.
AB  - Strong international health agreements and good planning created a structure and
      common procedure for nations involved in detection and evaluation of the
      emergence of influenza A (H1N1). This report describes a timeline of events that
      led to the determination of the epidemic as a public health emergency of
      international concern, following the agreed-upon procedures of the International
      Health Regulations. These events illustrate the need for sound international
      health agreements and should be a call to action for all nations to implement
      these agreements to the best of their abilities.

PMID- 19751577
TI  - Response to imported case of Marburg hemorrhagic fever, the Netherland.
AB  - On July 10, 2008, Marburg hemorrhagic fever was confirmed in a Dutch patient who
      had vacationed recently in Uganda. Exposure most likely occurred in the Python
      Cave (Maramagambo Forest), which harbors bat species that elsewhere in Africa
      have been found positive for Marburg virus. A multidisciplinary response team was
      convened to perform a structured risk assessment, perform risk classification of
      contacts, issue guidelines for follow-up, provide information, and monitor the
      crisis response. In total, 130 contacts were identified (66 classified as high
      risk and 64 as low risk) and monitored for 21 days after their last possible
      exposure. The case raised questions specific to international travel,
      postexposure prophylaxis for Marburg virus, and laboratory testing of contacts
      with fever. We present lessons learned and results of the follow-up serosurvey of
      contacts and focus on factors that prevented overreaction during an event with a
      high public health impact.

PMID- 19751579
TI  - Molecular epidemiology of rabies in Southern People's Republic of China.
AB  - In recent years, the number of human rabies cases in the People's Republic of
      China has increased during severe epidemics in 3 southern provinces (Guizhou,
      Guangxi, and Hunan). To analyze the causes of the high incidence of human rabies
      in this region, during 2005-2007, we collected 2,887 brain specimens from
      apparently healthy domestic dogs used for meat consumption in restaurants, 4
      specimens from suspected rabid dogs, and 3 from humans with rabies in the 3
      provinces. Partial nucleoprotein gene sequences were obtained from rabies
      positive specimens. Phylogenetic relationships and distribution of viruses were
      determined. We infer that the spread of rabies viruses from high-incidence
      regions, particularly by long-distance movement or transprovincial translocation
      of dogs caused by human-related activities, may be 1 cause of the recent massive
      human rabies epidemics in southern China.

PMID- 19751580
TI  - Serologic evidence of frequent human infection with WU and KI polyomaviruses.
AB  - WU polyomavirus (WUPyV) and KI polyomavirus (KIPyV) are novel human
      polyomaviruses. They were originally identified in human respiratory secretions,
      but the extent of human infection caused by these viruses has not been described
      to date. To determine the seroepidemiology of WUPyV and KIpyIV, we used an ELISA
      to screen serum samples from 419 patients at the St. Louis Children's Hospital
      and Barnes-Jewish Hospital during 2007-2008. The age-stratified deidentified
      samples were examined for antibodies to the major capsid proteins of WUPyV and
      KIPyV. Seropositivity for each virus was similar; antibody levels were high in
      the youngest age group (<6 months), decreased to a nadir in the next age group (6
      to <12 months), and then steadily increased with subsequent age groups,
      eventually reaching a plateau of approximate, equals 80% for WUPyV and
      approximate, equals 70% for KIPyV. These results demonstrate that both KIPyV and
      WUPyV cause widespread infection in the human population.

PMID- 19751581
TI  - Bordetella pertussis strains with increased toxin production associated with
      pertussis resurgence.
AB  - Before childhood vaccination was introduced in the 1940s, pertussis was a major
      cause of infant death worldwide. Widespread vaccination of children succeeded in
      reducing illness and death. In the 1990s, a resurgence of pertussis was observed
      in a number of countries with highly vaccinated populations, and pertussis has
      become the most prevalent vaccine-preventable disease in industrialized
      countries. We present evidence that in the Netherlands the dramatic increase in
      pertussis is temporally associated with the emergence of Bordetella pertussis
      strains carrying a novel allele for the pertussis toxin promoter, which confers
      increased pertussis toxin (Ptx) production. Epidemiologic data suggest that these
      strains are more virulent in humans. We discuss changes in the ecology of B.
      pertussis that may have driven this adaptation. Our results underline the
      importance of Ptx in transmission, suggest that vaccination may select for
      increased virulence, and indicate ways to control pertussis more effectively.

PMID- 19751582
TI  - Transgenic mice expressing porcine prion protein resistant to classical scrapie
      but susceptible to sheep bovine spongiform encephalopathy and atypical scrapie.
AB  - How susceptible pigs are to infection with sheep prions is unknown. We show,
      through transmission experiments in transgenic mice expressing porcine prion
      protein (PrP), that the susceptibility of this mouse model to bovine spongiform
      encephalopathy (BSE) can be enhanced after its passage in ARQ sheep, indicating
      that the pathogenicity of the BSE agent is modified after passage in sheep.
      Transgenic mice expressing porcine PrP were, nevertheless, completely resistant
      to infection with a broad panel of classical scrapie isolates from different
      sheep PrP genotypes and with different biochemical characteristics. The atypical
      (Nor98 like) isolate (SC-PS152) was the only scrapie isolate capable of
      transmission in these mice, although with a marked transmission barrier.
      Unexpectedly, the atypical scrapie agent appeared to undergo a strain phenotype
      shift upon transmission to porcine-PrP transgenic mice and acquired new strain
      properties, suggesting that atypical scrapie agent may exhibit different
      phenotypes depending on the host cellular PrP or other genetic factors.

PMID- 19751583
TI  - Slave trade and hepatitis B virus genotypes and subgenotypes in Haiti and Africa.
AB  - In Haiti, >90% of the population descended from African slaves. Of 7,147 Haitian
      pregnant women sampled, 44% of hepatitis B virus (HBV) infections were caused by
      genotype A1, which today is found mainly in eastern Africa. Twenty percent belong
      to a rare subgenotype, A5, which has been found only in the former Bight of
      Benin, a former primary slave trading post. Haitian A subgenotypes appear to have
      separated early from the African subgenotypes; the most prevalent genotype and
      subgenotype in West Africa today (E and A3, respectively) are rare in Haiti. This
      difference indicates that the dominant subgenotypes in Africa emerged in the
      general population only after the slave trade and explains the low genetic
      diversity of genotype E. The high prevalence of HBV genotype E in much of Africa
      further suggests that HBV hyperendemicity is a recent phenomenon, probably
      resulting from extensive use of unsafe needles.

PMID- 19751584
TI  - Recurrent zoonotic transmission of Nipah virus into humans, Bangladesh, 2001
      2007.
AB  - Human Nipah outbreaks recur in a specific region and time of year in Bangladesh.
      Fruit bats are the reservoir host for Nipah virus. We identified 23 introductions
      of Nipah virus into human populations in central and northwestern Bangladesh from
      2001 through 2007. Ten introductions affected multiple persons (median 10).
      Illness onset occurred from December through May but not every year. We
      identified 122 cases of human Nipah infection. The mean age of case-patients was
      27 years; 87 (71%) died. In 62 (51%) Nipah virus-infected patients, illness
      developed 5-15 days after close contact with another Nipah case-patient. Nine
      (7%) Nipah case-patients transmitted virus to others. Nipah case-patients who had
      difficulty breathing were more likely than those without respiratory difficulty
      to transmit Nipah (12% vs. 0%, p = 0.03). Although a small minority of infected
      patients transmit Nipah virus, more than half of identified cases result from
      person-to-person transmission. Interventions to prevent virus transmission from
      bats to humans and from person to person are needed.

PMID- 19751585
TI  - National outbreak of Acanthamoeba keratitis associated with use of a contact lens
      solution, United States.
AB  - An outbreak of Acanthamoeba keratitis, a rare, potentially blinding, corneal
      infection, was detected in the United States in 2007; cases had been increasing
      since 2004. A case-control study was conducted to investigate the outbreak. We
      interviewed 105 case-patients from 30 states and 184 controls matched
      geographically and by contact lens use. Available contact lenses, cases,
      solutions, and corneal specimens from case-patients were cultured and tested by
      molecular methods. In multivariate analyses, case-patients had significantly
      greater odds of having used Advanced Medical Optics Complete Moisture Plus
      (AMOCMP) solution (odds ratio 16.9, 95% confidence interval 4.8-59.5). AMOCMP
      manufacturing lot information was available for 22 case-patients, but none of the
      lots were identical. Three unopened bottles of AMOCMP tested negative for
      Acanthamoeba spp. Our findings suggest that the solution was not intrinsically
      contaminated and that its anti-Acanthamoeba efficacy was likely insufficient.
      Premarket standardized testing of contact lens solutions for activity against
      Acanthamoeba spp. is warranted.

PMID- 19751586
TI  - Entomologic and virologic investigation of Chikungunya, Singapore.
AB  - Local transmission of chikungunya, a debilitating mosquito-borne viral disease,
      was first reported in Singapore in January 2008. After 3 months of absence,
      locally acquired Chikungunya cases resurfaced in May 2008, causing an outbreak
      that resulted in a total of 231 cases by September 2008. The circulating viruses
      were related to East, Central, and South African genotypes that emerged in the
      Indian Ocean region in 2005. The first local outbreak was due to a wild-type
      virus (alanine at codon 226 of the envelope 1 gene) and occurred in an area where
      Aedes aegypti mosquitoes were the primary vector. Strains isolated during
      subsequent outbreaks showed alanine to valine substitution (A226V) and largely
      spread in areas predominated by Ae. albopictus mosquitoes. These findings led to
      a revision of the current vector control strategy in Singapore. This report
      highlights the use of entomologic and virologic data to assist in the control of
      chikungunya in disease-endemic areas.

PMID- 19751587
TI  - Reproducibility of serologic assays for influenza virus A (H5N1).
AB  - Hemagglutination-inhibition (HI) and neutralization are used to evaluate vaccines
      against influenza virus A (H5N1); however, poor standardization leads to
      interlaboratory variation of results. A candidate antibody standard (07/150) was
      prepared from pooled plasma of persons given clade 1 A/Vietnam/1194/2004 vaccine.
      To test human and sheep antiserum, 15 laboratories used HI and neutralization and
      reassortant A/Vietnam/1194/2004, A/turkey/Turkey/1/2005 (clade 2.2), and
      A/Anhui/1/2005 (clade 2.3.4) viruses. Interlaboratory variation was observed for
      both assays, but when titers were expressed relative to 07/150, overall
      percentage geometric coefficient of variation for A/Vietnam/1194/2004 was reduced
      from 125% to 61% for HI and from 183% to 81% for neutralization. Lack of reduced
      variability to clade 2 antigens suggested the need for clade-specific standards.
      Sheep antiserum as a standard did not reliably reduce variability. The World
      Health Organization has established 07/150 as an international standard for
      antibody to clade 1 subtype H5 and has an assigned potency of 1,000 IU/ampoule.

PMID- 19751588
TI  - Increase in pneumococcus macrolide resistance, United States.
AB  - During year 6 (2005-2006) of the Prospective Resistant Organism Tracking and
      Epidemiology for the Ketolide Telithromycin surveillance study, 6,747
      Streptococcus pneumoniae isolates were collected at 119 centers. The
      susceptibility of these isolates to macrolides was compared with data from
      previous years. Macrolide resistance increased significantly in year 6 (35.3%)
      from the stable rate of approximately 30% for the previous 3 years (p<0.0001).
      Macrolide resistance increased in all regions of the United States and for all
      patient age groups. Rates were highest in the south and for children 0-2 years of
      age. Lower-level efflux [mef(A)]-mediated macrolide resistance decreased in
      prevalence to approximately 50%, and highly resistant [erm(B) + mef(A)] strains
      increased to 25%. Telithromycin and levofloxacin susceptibility rates were >99%
      and >98%, respectively, irrespective of genotype. Pneumococcal macrolide
      resistance in the United States showed its first significant increase since 2000.
      High-level macrolide resistance is also increasing.

PMID- 19751589
TI  - Dengue 1 virus and dengue hemorrhagic fever, French Polynesia, 2001.
AB  - An epidemic of dengue 1 virus (DENV-1) occurred in French Polynesia in 2001, 4
      years after a DENV-2 epidemic that ended in 1997. Surveillance data from
      hospitalized case-patients showed that case-patients with dengue hemorrhagic
      fever (DHF) exhibited a bimodal age distribution with 1 peak among infants 6-10
      months of age and a second peak at 4-11 years of age. The relative risk of DHF
      developing in children born before rather than after the DENV-2 epidemic was 186
      (95% confidence interval 26-1,324). Among children born toward the end of the
      DENV-2 epidemic, a strong temporal association was found between the month of
      birth and the risk of being hospitalized for DHF. This study documents epidemic
      pathogenicity associated with the sequence of DENV-2 infection followed by DENV-1
      infection.

PMID- 19751590
TI  - Strategy to enhance influenza surveillance worldwide.
AB  - The emergence of a novel strain of influenza virus A (H1N1) in April 2009 focused
      attention on influenza surveillance capabilities worldwide. In consultations
      before the 2009 outbreak of influenza subtype H1N1, the World Health Organization
      had concluded that the world was unprepared to respond to an influenza pandemic,
      due in part to inadequate global surveillance and response capacity. We describe
      a sentinel surveillance system that could enhance the quality of influenza
      epidemiologic and laboratory data and strengthen a country's capacity for
      seasonal, novel, and pandemic influenza detection and prevention. Such a system
      would 1) provide data for a better understanding of the epidemiology and extent
      of seasonal influenza, 2) provide a platform for the study of other acute febrile
      respiratory illnesses, 3) provide virus isolates for the development of vaccines,
      4) inform local pandemic planning and vaccine policy, 5) monitor influenza
      epidemics and pandemics, and 6) provide infrastructure for an early warning
      system for outbreaks of new virus subtypes.

PMID- 19751591
TI  - Invasive group B streptococcal disease in the elderly, Minnesota, USA, 2003-2007.
AB  - In Minnesota, incidence of invasive group B streptococcal disease was 3 times
      greater in older adults in long-term care facilities than in older adults in
      community settings (67.7/100,000 vs. 21.4/100,000) during 2003-2007. The overall
      case-fatality rate was 6.8%, and concurrent conditions were common among both
      groups.

PMID- 19751592
TI  - Epidemiologic study of Vibrio vulnificus infections by using variable number
      tandem repeats.
AB  - A 3-year environmental and clinical Vibrio vulnificus survey using simple
      sequence repeats typing shows that V. vulnificus biotype 3 constitutes
      approximately 21% of the bacterium population in tested aquaculture ponds as
      opposed to approximately 86% of clinical cases. Simple-sequence repeats proved to
      be a useful epidemiologic tool, providing information on the environmental source
      of the pathogen.

PMID- 19751593
TI  - Challenges of investigating community outbreaks of cyclosporiasis, British
      Columbia, Canada.
AB  - Investigations of community outbreaks of cyclosporiasis are challenged by case
      patients' poor recall of exposure resulting from lags in detection and the
      stealthy nature of food vehicles. We combined multiple techniques, including
      early consultation with food regulators, traceback of suspected items, and
      grocery store loyalty card records, to identify a single vehicle for a
      cyclosporiasis outbreak in British Columbia, Canada, in 2007.

PMID- 19751594
TI  - Shiga toxin-producing Escherichia coli, New Mexico, USA, 2004-2007.
AB  - Sporadic infection with Shiga toxin-producing Escherichia coli (STEC) in New
      Mexico increased from 0.9 cases per 100,000 population (95% confidence interval
      [CI] 0.5-1.36) in 2004 to 1.7 (95% CI 1.14-2.26) in 2007. Non-O157 STEC was more
      common in nonwhite residents, children <5 years of age, and urban residents.

PMID- 19751595
TI  - Chronic invasive aspergillosis caused by Aspergillus viridinutans.
AB  - Aspergillus viridinutans, a mold phenotypically resembling A. fumigatus, was
      identified by gene sequence analyses from 2 patients. Disease was distinct from
      typical aspergillosis, being chronic and spreading in a contiguous manner across
      anatomical planes. We emphasize the recognition of fumigati-mimetic molds as
      agents of chronic or refractory aspergillosis.

PMID- 19751596
TI  - Legionella pneumophila in rainwater on roads.
AB  - During rain, transient puddles form on roads, and this water is splashed into the
      air by moving vehicles. To determine whether this water contains Legionella
      pneumophila, we collected samples from roads. We found that L. pneumophila are
      abundant in these puddles, especially during warm weather.

PMID- 19751597
TI  - West Nile virus from blood donors, vertebrates, and mosquitoes, Puerto Rico,
      2007.
AB  - West Nile virus (WNV) was isolated from a human blood donor, a dead falcon, and
      mosquitoes in Puerto Rico in 2007. Phylogenetic analysis of the 4 isolates
      suggests a recent introduction of lineage I WNV that is closely related to WNV
      currently circulating in North America.

PMID- 19751598
TI  - Lobomycosis in man and lobomycosis-like disease in bottlenose dolphin, Venezuela.
AB  - We report 1 case of lobomycosis caused by Lacazia loboi in a fisherman and 1 case
      of lobomycosis-like disease in a bottlenose dolphin (Tursiops truncatus) along
      the coast of Venezuela. These findings suggest that the marine environment is a
      likely habitat for L. loboi and a reservoir for infection.

PMID- 19751599
TI  - Predictors of death after severe Streptococcus pyogenes infection.
AB  - An evaluation of the relative importance of host and pathogen factors on the
      survival rate of patients with invasive Streptococcus pyogenes infection found a
      number of clinical and demographic factors to be associated with risk for death.
      Some evidence suggested a seasonal pattern to patient survival rate.

PMID- 19751600
TI  - Human rabies and rabies in vampire and nonvampire bat species, Southeastern Peru,
      2007.
AB  - After a human rabies outbreak in southeastern Peru, we collected bats to estimate
      the prevalence of rabies in various species. Among 165 bats from 6 genera and 10
      species, 10.3% were antibody positive; antibody prevalence was similar in vampire
      and nonvampire bats. Thus, nonvampire bats may also be a source for human rabies
      in Peru.

PMID- 19751601
TI  - Avian influenza virus A (H5N1), detected through routine surveillance, in child,
      Bangladesh.
AB  - We identified avian influenza virus A (H5N1) infection in a child in Bangladesh
      in 2008 by routine influenza surveillance. The virus was of the same clade and
      phylogenetic subgroup as that circulating among poultry during the period. This
      case illustrates the value of routine surveillance for detection of novel
      influenza virus.

PMID- 19751602
TI  - Pigs as source for toxigenic Corynebacterium ulcerans.

PMID- 19751603
TI  - Campylobacter jejuni HS:23 and Guillain-Barre syndrome, Bangladesh.

PMID- 19751604
TI  - Enzootic Sparganosis in Guangdong, People's Republic of China.

PMID- 19751605
TI  - Human rhinovirus group C in hospitalized children, Singapore.

PMID- 19751606
TI  - Nondominant hemisphere encephalitis in patient with signs of viral meningitis,
      New York, USA.

PMID- 19751607
TI  - Tick-borne rickettsiosis in traveler returning from Honduras.

PMID- 19751608
TI  - KI and WU polyomaviruses in patients infected with HIV-1, Italy.

PMID- 19751609
TI  - Extreme drug resistance in Acinetobacter baumannii infections in intensive care
      units, South Korea.

PMID- 19751610
TI  - More diseases tracked by using Google Trends.

PMID- 19751611
TI  - Human-to-dog transmission of methicillin-resistant Staphylococcus aureus.

PMID- 19751612
TI  - Potential malaria reemergence, northeastern Thailand.

PMID- 19751613
TI  - Fatal borreliosis in bat caused by relapsing fever spirochete, United Kingdom.

PMID- 19751614
TI  - Past, present, and future of Japanese encephalitis.

PMID- 19751617
TI  - For the world does not yet censure those who tread the paths of dreams.

PMID- 19751618
TI  - Asymmetric localisation of planar polarity proteins: Mechanisms and consequences.
AB  - Planar polarisation of tissues is essential for many aspects of developmental
      patterning. It is regulated by a conserved group of core planar polarity
      proteins, which localise asymmetrically within cells prior to morphological signs
      of polarisation. A subset of these core proteins also interact across cell
      boundaries, mediating intercellular communication that co-ordinates polarity
      between neighbouring cells. Core protein localisation subsequently mediates
      changes in the actin cytoskeleton which lead to overt polarisation. In this
      review we discuss the mechanisms by which the core planar polarity proteins
      become asymmetrically localised, and the significance of this subcellular
      localisation for both intercellular communication and downstream effects on the
      cytoskeleton.

PMID- 19751619
TI  - Ischemia-modified albumin in the diagnosis of pulmonary embolism: an experimental
      study.
AB  - STUDY OBJECTIVE: We designed this experimental study to determine the value of
      ischemia-modified albumin in the diagnosis of pulmonary embolism. METHODS: Twenty
      four mature female New Zealand rabbits were divided into 4 groups, each
      consisting of 6 animals. These were classified into group 1 ,the control group;
      group 2, the deep venous thrombosis group; group 3, the deep venous thrombosis
      with pulmonary embolism group; and group 4, the pulmonary embolism-alone group.
      Deep venous thrombosis was produced by ligation of the iliac vein. To establish
      pulmonary embolism, 2 clots were administered from the iliac vein. Blood samples
      were taken from all the groups at hours 0, 1, 3, and 6 for ischemia-modified
      albumin measurement. RESULTS: Pulmonary embolism was established in all the
      rabbits in groups 3 and 4, and this was confirmed by tomographic and histologic
      findings. Measurement of mean ischemia-modified albumin levels for all rabbits at
      hours 0, 1, 3, and 6 revealed that mean ischemia-modified albumin levels in
      groups 3 and 4 were statistically significantly higher than those in groups 1 and
      2. There was no difference between the mean ischemia-modified albumin levels in
      groups 1 and 2 nor between groups 3 and 4. The alteration in ischemia-modified
      albumin levels over time was statistically significant. CONCLUSIONS: The results
      of our experimental study demonstrate that ischemia-modified albumin levels may
      be useful in the diagnosis of pulmonary embolism.

PMID- 19751620
TI  - Adult intimate partner violence perpetrators are significantly more likely to
      have witnessed intimate partner violence as a child than nonperpetrators.
AB  - BACKGROUND: In a previous study, no association was found between intimate
      partner violence (IPV) victims and being an adult who witnessed IPV as a child
      (ACW). OBJECTIVE: The objective of the present study was to determine whether
      perpetrators of IPV (Perps) could be identified in a busy emergency department
      (ED) and whether Perps were more likely than non-Perps to be ACWs. The hypothesis
      was that Perps differed significantly from non-Perps in being ACWs, in being
      victims of IPV, and in demographics. METHODS: The design was a cross-sectional
      cohort of patients presenting to an academic ED during randomized 4-hour shifts.
      A choice of computer touch screen data vs paper format was offered. Data
      collected included demographics as well as scales to determine whether subjects
      were a Perp, victim, and/or ACW of IPV. Six validated scales were used to screen
      and confirm victims, Perps, and ACWs. Predictor variables were ACW, ongoing IPV,
      and demographics. RESULTS: Two hundred thirty-six subjects were entered, 207 had
      complete data sets. Forty-four (19%) were Perps. By univariate analysis, there
      was a significant correlation of Perps and ACW (P = .001 by single question) and
      between Perp and being victims (P = .001). No other univariate variables were
      significantly correlated. By regression analysis, significant predictors of Perp
      included ACW and spouse drug abuse. CONCLUSIONS: The Perps were identified in a
      busy ED setting. Perps were significantly more likely than non-Perps to be ACWs,
      but not more likely to be victims. Spouse drug abuse and ACW were the 2
      significant predictors of Perp.

PMID- 19751621
TI  - Combination pharmacotherapy in the treatment of experimental cardiac arrest.
AB  - STUDY OBJECTIVES: Full recovery after cardiopulmonary resuscitation (CPR) is
      poor. We hypothesized that the coadministration of epinephrine, a beta-blocker
      such as atenolol, and a calcium sensitizer such as levosimendan during CPR would
      improve survival and postresuscitation myocardial function. METHODS: Ventricular
      fibrillation was induced in 60 piglets, which were left untreated for 8 minutes
      before attempted resuscitation. Animals were randomized into 4 groups (n = 15),
      to receive epinephrine (group E), epinephrine + atenolol (group E + A),
      epinephrine + levosimendan (group E + L) and epinephrine + atenolol +
      levosimendan (group E + A + L) during CPR. Electrical defibrillation was
      attempted 2 minutes after drug administration. RESULTS: Five animals in group E
      survived for 48 hours in comparison to 8 animals in groups E + A and E + L and 12
      animals in group E + A + L. Postresuscitation cardiac output was significantly
      better in the animals of group E + A + L. Troponin I remained significantly lower
      in groups E + A and E + A + L. Serum astroglial protein (S-100) and neuron
      specific enolase values in group E + L and E + A + L were statistically lower
      than those measured in groups E and E + A during the entire observation period.
      The neurologic alertness score was higher in group E + A + L compared to groups E
      and E + A. CONCLUSIONS: The administration of a drug combination of epinephrine +
      atenolol + levosimendan, when given during CPR, in a pig model of cardiac arrest,
      results in improved 48-hour survival and improves postresuscitation cardiac
      function.

PMID- 19751622
TI  - Predictors and outcomes of frequent chest pain unit users.
AB  - AIM: To determine predictors of frequent chest pain unit (CPU) users and to
      identify characteristics and outcomes of their CPU visits. PATIENTS AND METHODS:
      Observational prospective case-control study. Frequent CPU user was defined by 3
      or more CPU visits within the study year. A control patient and a control visit
      were randomly selected for each case patient and case visit. Demographic,
      clinical, and outcome variables were collected from medical record and phone
      interview performed in a 30-day interval. A multivariate logistic regression
      analysis was used to identify frequent CPU users' predictors. RESULTS: Of 1934
      patients presenting during the year, 80 (4.1%) met the definition for case
      patient. They accounted for 352 (13%) of 2709 CPU visits. Sixty-seven (83.7%)
      case patients and 71 (88.7%) control patients were contacted. The final
      predictors were the following: Karnofsky Performance Scale of 70 or lesser (odds
      ratio [OR], 5.24 [95% confidence interval {CI}, 1.71-16.06]), previous
      hospitalization (OR, 3.76 [95% CI, 1.49-9.49]), previously known coronary artery
      disease (OR, 3.72 [95% CI, 1.32-10.52]), and symptoms of depression (OR, 2.98
      [95% CI, 1.14-7.78]). Case visits were more likely at night (OR, 2.41 [95% CI,
      1.64- 3.52]), generated more diagnostic uncertainty (OR, 2.39 [95% CI, 1.71
      3.35]), but did not increase the need of hospital admission. CONCLUSIONS:
      Frequent CPU user is associated with previously known coronary artery disease,
      previous hospitalization, impaired performance status, and presence of symptoms
      of depression. They are more likely to arrive on CPU at night and generate more
      diagnostic uncertainty.

PMID- 19751623
TI  - Implementation of a bundle of actions to improve adherence to the Surviving
      Sepsis Campaign guidelines at the ED.
AB  - PURPOSES: We had previously demonstrated surviving sepsis campaign guidelines had
      not had enough impact at our Emergency Department. BASIC PROCEDURES: Actions
      directed to increase the qualification of our staff and residents, to facilitate
      guidelines divulgation and to improve spatial conditions by creating a High
      Dependency Unit were implemented as a bundle. The impact of these actions on the
      achievement of early objectives of the campaign and on mortality was analyzed.
      MAIN FINDINGS: Following campaign guidelines was more frequent after the
      implementation of these actions, as shown by less restrictive fluids
      administration for more severe cases (P = .001), earlier administration of
      antibiotics (P = .001) and lactate determination rate (46% vs. 12%). In-hospital
      mortality difference did not reach statistical difference. Physicians were able
      to identify high-risk patients on clinical grounds. PRINCIPAL CONCLUSIONS: The
      bundle of actions has had a moderate beneficial effect on our Emergency
      Department. High Dependency Units are useful for managing patients not fulfilling
      criteria for Intensive Care Unit admission.

PMID- 19751624
TI  - Prediction of myocardial infarction risk in older patients with acute coronary
      syndrome.
AB  - PURPOSES: To identify bedside variables that aid in diagnosis of acute coronary
      syndrome (ACS) and might facilitate rapid triage of patients aged > or = 65
      years. BASIC PROCEDURES: Prospective, observational study of consecutive patients
      aged > or = 65 years with suspicion of ACS presenting to our emergency department
      (ED). Patients' medical characteristics were collected at baseline and during a 1
      month follow-up period. We identified variables independently associated with ACS
      by multivariate analyses and bootstrapping techniques. MAIN FINDINGS: Among 399
      patients, 124 (31.1%) received a diagnosis of ACS (61 acute myocardial
      infarction, 63 unstable angina). We surveyed multiple clinical and ECG variables
      to develop a predictive model which included the following variables: male sex,
      history of coronary artery disease, typical chest pain, dyspnea, epigastric pain,
      pathological Q-wave, ST-segment elevation (area under the receiver operating
      characteristic curve (AUC) 0.79, 95% confidence interval 0.71 to 0.82). With the
      addition of cardiac troponin I to the model the AUC increased to 0.83 (0.79 to
      0.88). We used these findings to create the Heart Attack Risk for aged Patient
      (HARP) scale. Our data suggest that patients with a low HARP score might be
      safely managed without further testing. PRINCIPAL CONCLUSIONS: A model based on
      variables easily available at ED presentation from history, physical examination,
      and electrocardiography, can help ED physicians to identify seniors at very low
      risk of ACS.

PMID- 19751625
TI  - Facilitated angioplasty with combo therapy among patients with ST-segment
      elevation myocardial infarction: a meta-analysis of randomized trials.
AB  - INTRODUCTION: Time to treatment has been shown to be a major determinant of
      mortality in primary angioplasty. The aim of the current study was to perform a
      meta-analysis of randomized trials evaluating the benefits from pharmacologic
      facilitation with adjunctive glycoprotein (Gp) IIb-IIIa inhibitors + reduced
      lytic therapy vs adjunctive Gp IIb-IIIa inhibitors among patients with ST-segment
      elevation myocardial infarction (MI). METHODS: We obtained results from all
      randomized trials comparing facilitated PCI with adjunctive Gp IIb-IIIa
      inhibitors and reduced lytic therapy vs adjunctive Gp IIb-IIIa inhibitors among
      patients with ST-segment elevation MI (STEMI). The literature was scanned by
      formal searches of electronic databases (MEDLINE and CENTRAL) from January 1990
      to December 2007. The following key words were used: randomized trial, MI,
      reperfusion, primary angioplasty, pharmacologic facilitation, facilitated
      angioplasty, combo therapy, fibrinolysis, thrombolysis, half-dose lytic therapy,
      duteplase, reteplase, tenecteplase, alteplase, abciximab, tirofiban,
      eptifibatide, and Gp IIb-IIIa inhibitors. Angiographic end points were the rate
      of preprocedural and postprocedural thrombolysis in MI (TIMI) 3 flow. Clinical
      end points assessed were mortality and reinfarction at 30-day follow-up, whereas
      major bleeding complications were assessed as safety end point. No language
      restriction was applied. RESULTS: We identified 6 randomized trials, including
      2684 patients with STEMI. Even though combo therapy was associated with a
      significant improvement in preprocedural TIMI 3 flow (44.3% vs 15.2%, P < .0001,
      P(het) < .0001), it did not improve the rate of postprocedural TIMI 3 flow (91.5%
      vs 91.2%, P = .12). No benefits were observed in terms of 30-day mortality (4.2%
      vs 4.6%, P = .66, P(het) = .22) and/or 30-day reinfarction (1.3% vs 1.3%, P =
      .84). However, combo therapy was associated with higher risk of major bleeding
      complications (5.8% vs 3.9%, P = .03). CONCLUSIONS: This meta-analysis shows that
      among patients with STEMI undergoing primary angioplasty, pharmacologic
      facilitation with combined reduced-dose thrombolytic therapy and Gp IIbIIIa
      inhibitors is not superior to Gp IIb-IIIa inhibitors alone and, thus, may not be
      routinely recommended. However, future randomized trials should investigate
      whether this strategy may further improve outcome when applied within the first
      hours from symptoms onset, especially in patients undergoing transferring for
      primary angioplasty.

PMID- 19751626
TI  - A study of the workforce in emergency medicine: 2007.
AB  - INTRODUCTION: This study was undertaken to describe the current status of the
      emergency medicine workforce in the United States. METHODS: Surveys were
      distributed in 2008 to 2619 emergency department (ED) medical directors and nurse
      managers in hospitals in the 2006 American Hospital Association database.
      RESULTS: Among ED medical directors, 713 responded, for a 27.2% response rate.
      Currently, 65% of practicing emergency physicians are board certified by the
      American Board of Emergency Medicine or the American Osteopathic Board of
      Emergency Medicine. Among those leaving the practice, the most common reasons
      cited for departure include geographic relocation (46%) and better pay (29%).
      Approximately 12% of the ED physician workforce is expected to retire in the next
      5 years. Among nurse managers, 548 responded, for a 21% response rate. Many
      nurses (46%) have an associate degree as their highest level of education, 28%
      have a BSN, and 3% have a graduate degree (MSN or higher). Geographic relocation
      (44%) is the leading reason for changing employment. Emergency department annual
      volumes have increased by 49% since 1997, with a mean ED volume of 32 281 in
      2007. The average reported ED length of stay is 158 minutes from registration to
      discharge and 208 minutes from registration to admission. Emergency department
      spent an average of 49 hours per month in ambulance diversion in 2007. Boarding
      is common practice, with an average of 318 hours of patient boarding per month.
      CONCLUSIONS: In the past 10 years, the number of practicing emergency physicians
      has grown to more than 42 000. The number of board-certified emergency physicians
      has increased. The number of annual ED visits has risen significantly.

PMID- 19751627
TI  - Prognostic significance of brain natriuretic peptide obtained in the ED in
      patients with SIRS or sepsis.
AB  - PURPOSE: The study was conducted to know the significance of brain natriuretic
      peptide (BNP) for prognosis of septic patients. METHODS: The subjects were 1000
      patients selected in emergency department of Beijing Chaoyang Hospital of the
      Capital Medical University (Beijing, China) and were classified into 3 groups as
      follows: systemic inflammatory response syndrome (SIRS), non-SIRS, and sepsis
      groups. Plasma serum brain natriuretic peptide (BNP) levels and the positive
      detection rates of BNP were examined. The BNP level of 100 pg/mL or more was
      regarded as positive, and then the positive detection rates of BNP of these
      groups were compared. The prognostic values of BNP and APACHE (Acute physiology
      and chronic health evaluation) II score for the 28-day mortality were
      investigated, and their cutoff values for death were determined. RESULTS: There
      were significant differences in the positive detection rates of BNP between any 2
      groups and in 28-day mortality between the patients with SIRS and non-SIRS
      groups. The BNP level had positive correlation to APACHE II score in 3 groups.
      Brain natriuretic peptide level of more than 113 pg/mL was independent predictor
      of death in septic patients. CONCLUSION: The positive rates of BNP in SIRS and
      septic patients were significantly higher than that of non-SIRS patients, and
      this is an index for unfavorable prognosis in septic patients.

PMID- 19751628
TI  - BNP this, BNP that... Now in sepsis?

PMID- 19751629
TI  - ED patient estimation of blood loss.
AB  - PURPOSE: Emergency department (ED) patients frequently estimate blood loss. How
      such information should guide evaluation and management, however, is unclear. The
      objective of this study was to examine ED patient accuracy in estimating blood
      loss on different surfaces. METHODS: A convenience sample of 100 ED patients were
      asked to estimate the amount of moulage blood present in 4 scenarios: 178 mL
      spilled in a baking sheet on the floor; 5 mL in 2.5 mL of mucous in a tissue; 119
      mL on a t-shirt; and 119 mL in a commode filled with water. RESULTS: The mean
      percent error for all estimates was 412% with a range of 0% to 1080%. Estimates
      were within 100% of the actual amount 44% of the time. Eleven percent of
      assessments were correct and 70% were overestimates. CONCLUSION: Emergency
      department patients do not estimate blood loss well in a variety of scenarios,
      erring on the side of overestimation.

PMID- 19751630
TI  - Percutaneous coronary intervention-related time delay, patient's risk profile,
      and survival benefits of primary angioplasty vs lytic therapy in ST-segment
      elevation myocardial infarction.
AB  - BACKGROUND: Previous reports have suggested an impact of patient's risk profile
      and percutaneous coronary intervention (PCI)-related time delay on the benefits
      of primary angioplasty as compared with fibrinolysis. However, several factors,
      such as inappropriate interpretation and definition of delays, missing currently
      available trials, and arguable risk-benefit analysis, limit the value of these
      reports. Thus, the aim of the current review is to assess whether the prognostic
      impact of PCI-related time delay may vary according to patient's risk profile,
      presentation delay, and type of lytic therapy. METHODS: We obtained results from
      all randomized trials comparing fibrinolysis and primary angioplasty in ST
      segment elevation myocardial infarction. The literature was scanned by formal
      searches of electronic databases (MEDLINE and CENTRAL) for papers published from
      January 1990 to April 2007. The following key words were used: randomized trial,
      myocardial infarction, reperfusion, primary angioplasty, rescue angioplasty,
      fibrinolysis, thrombolysis, duteplase, reteplase, tenecteplase, and alteplase.
      Major clinical end point assessed was mortality at 30-day follow-up. The
      relationship between mortality benefits from primary angioplasty, patient's risk
      profile, and PCI-related time delay was evaluated by using a weighted least
      square regression in which results from each trial were weighted by the square
      root of the number of patients of each trial. RESULTS: A total of 27 trials were
      finally included, with 4399 patients randomized to primary angioplasty and 4474
      patients randomized to fibrinolysis. The relationship between the benefits from
      primary angioplasty and PCI-related time changed according to risk profile. The
      higher the risk profile, the larger the reduction in mortality benefits from
      primary angioplasty as compared with fibrinolysis per each 10 minutes of PCI
      related time delay (0.75%, 0.45%, and 0%, in high-, medium-, and low-risk
      patients, respectively). Furthermore, the impact was observed only in trials
      enrolling patients within the first 6 hours from symptom onset. CONCLUSIONS: When
      primary angioplasty is selected as reperfusion strategy, all efforts should be
      attempted to shorten time-to-treatment, particularly in medium- or high-risk
      patients and in early presenters, because in these patients, a larger loss of
      mortality benefits as compared with fibrinolysis is observed per each 10 minutes
      of PCI-related time delay.

PMID- 19751631
TI  - The current management of skin tears.
AB  - Each year, there are more than 1 million skin tears among the elderly and
      disabled. Because of their fragile nature, management of skin tears can be very
      challenging. Methods of wound closure should minimize additional trauma to the
      skin and promote an optimal wound healing environment while minimizing the risk
      of infection. The current article reviews the etiology, risk factors,
      classification, and therapeutic options for treating skin tears. We also review
      preventive measures to help reduce the incidence of skin tears.

PMID- 19751632
TI  - The evolution of electrocardiographic changes in ST-segment elevation myocardial
      infarction.
AB  - Acute myocardial infarction (AMI) is a not uncommon diagnosis in the emergency
      department. During ST-segment elevation AMI (STEMI), the electrocardiogram (ECG)
      typically follows a progression of abnormality, beginning with hyperacute T waves
      and culminating with ST-segment elevation; pathologic Q waves can appear early
      and/or late in the process. Other findings include T-wave inversion and ST
      segment depression which can occur before, during, or after the STEMI event. The
      evolution of ECG through these changes can occur rapidly after coronary artery
      occlusion. The emergency physician should be aware of the ECG findings that
      characterize the evolution of an STEMI with a sound understanding of the
      associated pathophysiology and clinical implication. This review discusses the
      changing ECG during an AMI. The pathogenesis of these findings is discussed.
      Finally, the clinical implications at each stage are reviewed.

PMID- 19751633
TI  - TASER study results do not reflect real-life restraint situations.

PMID- 19751635
TI  - Electrocardiogram manifestation of spontaneous pneumothorax.

PMID- 19751636
TI  - A potential pitfall in the diagnosis of renal colic: renal infarction.

PMID- 19751637
TI  - Fatal exertional heat stroke successfully treated with cold hemofiltration: a
      case report.

PMID- 19751638
TI  - Fatal pneumococcal Waterhouse-Friderichsen syndrome in a vaccinated adult with
      congenital asplenia.

PMID- 19751639
TI  - Ataxia associated with spurious hyperchloremia: the one behind the scene.

PMID- 19751640
TI  - Spontaneous self-ignition in a case of acute aluminium phosphide poisoning.

PMID- 19751641
TI  - Colonic necrosis due to sodium polystyrene sulfate (Kayexalate).

PMID- 19751642
TI  - Simultaneous bilateral femoral arterial emboli presenting with acute paraplegia:
      an uncommon case.

PMID- 19751643
TI  - Spontaneous bilateral carotid artery dissection in a woman presenting with
      isolated headache.

PMID- 19751644
TI  - Muscle-specific tyrosine kinase-antibody-positive myasthenic crisis with detailed
      electrophysiologic studies.

PMID- 19751645
TI  - Successful treatment of monkshood (aconite napel) poisoning with magnesium
      sulfate.

PMID- 19751646
TI  - A patient with recurrent episodes of abdominal pain and hypovolemic shock.

PMID- 19751647
TI  - Systemic bleeding in a patient with enoxaparin-induced thrombocytopenia.

PMID- 19751648
TI  - Successful treatment of repaglinide-induced hypoglycemia with octreotide.

PMID- 19751649
TI  - Acute colonic pseudo-obstruction (Ogilvie's syndrome): radiologic diagnosis and
      medical treatment with neostigmine. Report of 4 cases.

PMID- 19751650
TI  - Damage of cerebellar white matter due to carbon monoxide poisoning: a case
      report.

PMID- 19751651
TI  - Importance of cerebrospinal fluid analysis in stat laboratory.

PMID- 19751652
TI  - Cerebral vein thrombosis and Guillain-Barre syndrome: a challenging association.

PMID- 19751653
TI  - Priapism associated with Latrodectus mactans envenomation.

PMID- 19751654
TI  - Value of Liu's stain in rapid diagnosis of Plasmodium ovale infection.

PMID- 19751655
TI  - Light-dark cycle memory in the mammalian suprachiasmatic nucleus.
AB  - The mammalian circadian oscillator, or suprachiasmatic nucleus (SCN), contains
      several thousand clock neurons in its ventrolateral division, many of which are
      spontaneous oscillators with period lengths that range from 22 to 28 h. In
      complete darkness, this network synchronizes through the exchange of action
      potentials that release vasoactive intestinal polypeptide, striking a compromise,
      free-running period close to 24 h long. We entrained Siberian hamsters to various
      light-dark cycles and then tracked their activity into constant darkness to show
      that they retain a memory of the previous light-dark cycle before returning to
      their own free-running period. Employing Leloup-Goldbeter mammalian clock neurons
      we model the ventrolateral SCN network and show that light acting weakly upon a
      strongly rhythmic vasoactive intestinal polypeptide oscillation can explain the
      observed light-dark cycle memory. In addition, light is known to initiate a
      mitogen-activated protein kinase signaling cascade that induces transcription of
      both per and mkp1 phosphatase. We show that the ensuing phosphatase-kinase
      interaction can account for the dead zone in the mammalian phase response curve
      and hypothesize that the SCN behaves like a lock-in amplifier to entrain to the
      light edges of the circadian day.

PMID- 19751656
TI  - Influence of internal capsid pressure on viral infection by phage lambda.
AB  - Ejection of the genome from the virus, phage lambda, is the initial step in the
      infection of its host bacterium. In vitro, the ejection depends sensitively on
      internal pressure within the virus capsid; however, the in vivo effect of
      internal pressure on infection of bacteria is unknown. Here, we use microfluidics
      to monitor individual cells and determine the temporal distribution of lysis due
      to infection as the capsid pressure is varied. The lysis probability decreases
      markedly with decreased capsid pressure. Of interest, the average lysis times
      remain the same but the distribution is broadened as the pressure is lowered.

PMID- 19751657
TI  - Frequency spectrum of transepithelial potential difference reveals transport
      related oscillations.
AB  - How epithelia transport fluid is a fundamental issue that is unresolved.
      Explanations offered include molecular engines, local transcellular osmosis,
      local paracellular osmosis, and paracellular fluid transport. On the basis of
      experimental and theoretical work done on corneal endothelium, a fluid
      transporting epithelium, we suggest electroosmotic coupling at the level of the
      intercellular junctions driven by the transendothelial electrical potential
      difference as an explanation of paracellular fluid transport. We collect
      frequency spectra of that potential difference in real-time. For what we believe
      is the first time for any epithelium, we report that, unexpectedly, the potential
      difference displays oscillations at many characteristic frequencies. We also show
      that on both stimulating cell activity and inhibiting ion transport mechanisms,
      there are corresponding changes in the oscillations amplitudes that mirror
      changes known previously in rates of fluid transport. We believe these findings
      provide a novel tool to study the kinetics of electrogenic elements such as
      channels and transporters, which from this evidence would give rise to current
      oscillations with characteristic periods going from 150 ms to 8 s.

PMID- 19751658
TI  - RGS9 concentration matters in rod phototransduction.
AB  - The transduction of light by retinal rods and cones is effected by homologous G
      protein cascades whose rates of activation and deactivation determine the
      sensitivity and temporal resolution of photoreceptor signaling. In mouse rods,
      the rate-limiting step of deactivation is hydrolysis of GTP by the G-protein
      effector complex, catalyzed by the RGS9 complex. Here, we incorporate a
      "Michaelis module" describing the RGS9 reaction into the conventional scheme for
      phototransduction and show that this augmented scheme can account precisely for
      the dominant recovery rate of intact rods in which RGS9 expression varies over a
      20-fold range. Furthermore, by screening the parameter space of the scheme with
      maximum-likelihood methodology, we tested specific hypotheses about the rate
      constant for rhodopsin deactivation, and about the forward, reverse, and
      catalytic constants for RGS9-mediated G-protein deactivation. These tests
      reliably exclude lifetimes > approximately 50 ms for rhodopsin, and reveal that
      the dominant time constant of rod photoresponse recovery is 1/(V(max)/K(m)) for
      the RGS9 reaction, with k(cat)/K(m) approximately = 0.04 microm(2) s(-1) and
      k(cat) > 35 s(-1) (or K(m) > 840 microm(-2)). All together, the new kinetic
      scheme and analysis explain how and why RGS9 concentration matters in rod
      phototransduction, and they provide a framework for understanding the molecular
      mechanisms that rate-limit deactivation in other G-protein systems.

PMID- 19751659
TI  - Anomalous dynamics of melanosomes driven by myosin-V in Xenopus laevis
      melanophores.
AB  - The organization of the cytoplasm is regulated by molecular motors, which
      transport organelles and other cargoes along cytoskeleton tracks. In this work,
      we use single particle tracking to study the in vivo regulation of the transport
      driven by myosin-V along actin filaments in Xenopus laevis melanophores.
      Melanophores have pigment organelles or melanosomes, which, in response to
      hormones, disperse in the cytoplasm or aggregate in the perinuclear region. We
      followed the motion of melanosomes in cells treated to depolymerize microtubules
      during aggregation and dispersion, focusing the analysis on the dynamics of these
      organelles in a time window not explored before to our knowledge. These data
      could not be explained by previous models that only consider active transport. We
      proposed a transport-diffusion model in which melanosomes may detach from actin
      tracks and reattach to nearby filaments to resume the active motion after a given
      time of diffusion. This model predicts that organelles spend approximately 70%
      and 10% of the total time in active transport during dispersion and aggregation,
      respectively. Our results suggest that the transport along actin filaments and
      the switching from actin to microtubule networks are regulated by changes in the
      diffusion time between periods of active motion driven by myosin-V.

PMID- 19751660
TI  - Calcium-actin waves and oscillations of cellular membranes.
AB  - We propose a mechanism for the formation of membrane oscillations and traveling
      waves, which arise due to the coupling between the actin cytoskeleton and the
      calcium flux through the membrane. In our model, the fluid cell membrane has a
      mobile but constant population of proteins with a convex spontaneous curvature,
      which act as nucleators of actin polymerization and adhesion. Such a continuum
      model couples the forces of cell-substrate adhesion, actin polymerization,
      membrane curvature, and the flux of calcium through the membrane. Linear
      stability analysis shows that sufficiently strong coupling among the calcium,
      membrane, and protein dynamics may induce robust traveling waves on the membrane.
      This result was checked for a reduced feedback scheme and is compared to the
      results without the effects of calcium, where permanent phase separation without
      waves or oscillations is obtained. The model results are compared to the
      published observations of calcium waves in cell membranes, and a number of
      testable predictions are proposed.

PMID- 19751661
TI  - Selective filtering of particles by the extracellular matrix: an electrostatic
      bandpass.
AB  - The transport of microscopic particles such as growth factors, proteins, or drugs
      through the extracellular matrix (ECM) is based on diffusion, a ubiquitous
      mechanism in nature. The ECM shapes the local distribution of the transported
      macromolecules and at the same time constitutes an important barrier toward
      infectious agents. To fulfill these competing tasks, the hydrogels have to employ
      highly selective filtering mechanisms. Yet, the underlying microscopic principles
      are still an enigma in cell biology and drug delivery. Here, we show that the
      extracellular matrix presents an effective electrostatic bandpass, suppressing
      the diffusive motion of both positively and negatively charged objects. This
      mechanism allows uncharged particles to easily diffuse through the matrix, while
      charged particles are effectively trapped. However, by tuning the strength of
      this physical interaction of the particles with the biopolymer matrix, the
      microscopic mobility of formerly trapped particles can be rescued on demand.
      Moreover, we identify heparan sulfate chains to be one important key factor for
      the barrier function of the extracellular matrix. We propose that localized
      charge patches in the ECM are responsible for its highly unspecific but strongly
      selective filtering effect. Such localized interactions could also account for
      the observed tunability and selectivity of many other important permeability
      barriers that are established by biopolymer-based hydrogels, e.g., the mucus
      layer of endothelial cells or the hydrogel in the nuclear core complex.

PMID- 19751662
TI  - Sarcomere mechanics in capillary endothelial cells.
AB  - Tension generation in endothelial cells of the aorta, spleen, and eye occurs in
      actin stress fibers, and is necessary for normal cell function. Sarcomeres are
      the tension-generating units of actin stress fibers in endothelial cells. How
      sarcomeres generate and maintain tension in stress fibers is not well understood.
      Using femtosecond laser ablation, we severed living stress fibers and measured
      sarcomere contraction under zero tension. The length of the sarcomere decreased
      in two phases: an instantaneous initial response, followed by a slower change in
      length attributed to myosin activity. The latter phase ceased abruptly after a
      minimum sarcomere length was reached, suggesting a rigid resistance that prevents
      further contraction. Furthermore, severed, contracted stress fibers did not relax
      when treated with myosin inhibitors, indicating that contracted stress fibers do
      not store elastic potential energy. These novel measurements combined with
      modeling suggest that myosin-generated forces in adjacent sarcomeres are directly
      in balance, and argue against sarcomere models with springlike elements in
      parallel with myosin contractile elements. We propose a new model for tension
      generation in the sarcomere, which provides a mechanistic interpretation for our
      observations and previous observations of inhomogeneous sarcomere contraction and
      apparent stress fiber viscoelastic behavior.

PMID- 19751663
TI  - Modeling neuronal nicotinic and GABA receptors: important interface salt-links
      and protein dynamics.
AB  - Protein motions in the Cys-loop ligand-gated ion receptors that govern the gating
      mechanism are still not well understood. The details as to how motions in the
      ligand-binding domain are translated to the transmembrane domain and how subunit
      rotations are linked to bring about the cooperative movements involved in gating
      are under investigation. Homology models of the alpha4beta2 nicotinic
      acetylcholine (nACh) and beta2alpha1gamma2 GABA receptors were constructed based
      on the torpedo neuromuscular-like nicotinic receptor structure. The template
      constructed for the full electron microscopy structure must be considered more
      reliable for structure-function studies due to the preservation of the E45-R209
      salt-link. Many other salt-links are seen to transiently form, including
      switching off of the E45-R209 link, within a network of potential salt-links at
      the binding domain to the transmembrane domain interface region. Several
      potentially important intersubunit salt-links form in both the nAChR and GABAR
      structures during the simulation and appear conserved across many subunit
      combinations, such as the salt-link between alpha4.E262 and beta2.K255 in nAChR
      (beta2.E262 and alpha1.K263 in GABAR), at the top of the pore-lining M2 helices,
      and the intersubunit link of R210 on the M1-linker to E168 on the beta8-sheet of
      the adjacent subunit in the GABA receptor (E175-K46 being the structurally
      equivalent link in the nAChR, with reversed polarity). A network of other salt
      links may be vital for transmitting the cooperative gating motions between
      subunits that become biased upon ligand binding. The changes seen in the
      simulations suggest that this network of salt-links helps to set limits and
      specific states for the conformational changes involved in gating of the
      receptor. We hope that these hypotheses will be tested experimentally in the near
      future.

PMID- 19751664
TI  - Effects of charge on osmotic reflection coefficients of macromolecules in fibrous
      membranes.
AB  - A model based on continuum hydrodynamics and electrostatics was developed to
      predict the combined effects of molecular charge and size on the osmotic
      reflection coefficient (sigma(o)) of a macromolecule in a fibrous membrane, such
      as a biological hydrogel. The macromolecule was represented as a sphere with a
      constant surface charge density, and the membrane was assumed to consist of an
      array of parallel fibers of like charge, also with a constant surface charge
      density. The flow was assumed to be parallel to the fiber axes. The effects of
      charge were included by computing the electrostatic free energy for a sphere
      interacting with an array of fibers. It was shown that this energy could be
      approximated using a pairwise additivity assumption. Results for sigma(o) were
      obtained for two types of negatively charged fibers, one with properties like
      those of glycosaminoglycan chains, and the other for thicker fibers having a
      range of charge densities. Using physiologically reasonable fiber spacings and
      charge densities, sigma(o) for bovine serum albumin in either type of fiber array
      was shown to be much larger than that for an uncharged system. Given the close
      correspondence between sigma(o) and the reflection coefficient for filtration,
      the results suggest that the negative charge of structures such as the
      endothelial surface glycocalyx is important in minimizing albumin loss from the
      circulation.

PMID- 19751665
TI  - Flickering analysis of erythrocyte mechanical properties: dependence on
      oxygenation level, cell shape, and hydration level.
AB  - Erythrocytes (red blood cells) play an essential role in the respiratory
      functions of vertebrates, carrying oxygen from lungs to tissues and CO(2) from
      tissues to lungs. They are mechanically very soft, enabling circulation through
      small capillaries. The small thermally induced displacements of the membrane
      provide an important tool in the investigation of the mechanics of the cell
      membrane. However, despite numerous studies, uncertainties in the interpretation
      of the data, and in the values derived for the main parameters of cell mechanics,
      have rendered past conclusions from the fluctuation approach somewhat
      controversial. Here we revisit the experimental method and theoretical analysis
      of fluctuations, to adapt them to the case of cell contour fluctuations, which
      are readily observable experimentally. This enables direct measurements of
      membrane tension, of bending modulus, and of the viscosity of the cell cytoplasm.
      Of the various factors that influence the mechanical properties of the cell, we
      focus here on: 1), the level of oxygenation, as monitored by Raman spectrometry;
      2), cell shape; and 3), the concentration of hemoglobin. The results show that,
      contrary to previous reports, there is no significant difference in cell tension
      and bending modulus between oxygenated and deoxygenated states, in line with the
      softness requirement for optimal circulatory flow in both states. On the other
      hand, tension and bending moduli of discocyte- and spherocyte-shaped cells differ
      markedly, in both the oxygenated and deoxygenated states. The tension in
      spherocytes is much higher, consistent with recent theoretical models that
      describe the transitions between red blood cell shapes as a function of membrane
      tension. Cell cytoplasmic viscosity is strongly influenced by the hydration
      state. The implications of these results to circulatory flow dynamics in
      physiological and pathological conditions are discussed.

PMID- 19751666
TI  - New insights into BAR domain-induced membrane remodeling.
AB  - Mesoscopic simulations and electron microscopy of N-BAR domain-induced liposome
      remodeling are used to characterize the process of liposome tubulation and
      vesiculation. The overall process of membrane remodeling is found to involve
      complex couplings among the N-BAR protein density, the degree of N-BAR
      oligomerization, and the membrane density. A comparison of complex remodeled
      liposome structures from mesoscopic simulations with those measured by electron
      microscopy experiments suggests that the process of membrane remodeling can be
      described via an appropriate mesoscopic free energy framework. Liposome
      remodeling more representative of F-BAR domains is also presented within the
      mesoscopic simulation framework.

PMID- 19751667
TI  - Modeling membrane deformations and lipid demixing upon protein-membrane
      interaction: the BAR dimer adsorption.
AB  - We use a self-consistent mean-field theory, designed to investigate membrane
      reshaping and lipid demixing upon interaction with proteins, to explore BAR
      domains interacting with large patches of lipid membranes of heterogeneous
      compositions. The computational model includes contributions to the system free
      energy from electrostatic interactions and elastic energies of the membrane, as
      well as salt and lipid mixing entropies. The results from our simulation of a
      single adsorbing Amphiphysin BAR dimer indicate that it is capable of stabilizing
      a significantly curved membrane. However, we predict that such deformations will
      occur only for membrane patches that have the inherent propensity for high
      curvature, reflected in the tendency to create local distortions that closely
      match the curvature of the BAR dimer itself. Such favorable preconditioning for
      BAR-membrane interaction may be the result of perturbations such as local lipid
      demixing induced by the interaction, or of a prior insertion of the BAR domain's
      amphiphatic N-helix. From our simulations it appears that local segregation of
      charged lipids under the influence of the BAR dimer cannot produce high enough
      asymmetry between bilayer leaflets to induce significant bending. In the absence
      of additional energy contributions that favor membrane asymmetry, the membrane
      will remain nearly flat upon single BAR dimer adsorption, relative to the
      undulation expected from thermal fluctuations. Thus, we conclude that the N-helix
      insertions have a critical mechanistic role in the local perturbation and curving
      of the membrane, which is then stabilized by the electrostatic interaction with
      the BAR dimer. We discuss how these results can be used to estimate the tendency
      of BARs to bend membranes in terms of a spatially nonisotropic spontaneous
      curvature.

PMID- 19751668
TI  - Bending stiffness depends on curvature of ternary lipid mixture tubular
      membranes.
AB  - Lipid and protein sorting and trafficking in intracellular pathways maintain
      cellular function and contribute to organelle homeostasis. Biophysical aspects of
      membrane shape coupled to sorting have recently received increasing attention.
      Here we determine membrane tube bending stiffness through measurements of tube
      radii, and demonstrate that the stiffness of ternary lipid mixtures depends on
      membrane curvature for a large range of lipid compositions. This observation
      indicates amplification by curvature of cooperative lipid demixing. We show that
      curvature-induced demixing increases upon approaching the critical region of a
      ternary lipid mixture, with qualitative differences along two roughly orthogonal
      compositional trajectories. Adapting a thermodynamic theory earlier developed by
      M. Kozlov, we derive an expression that shows the renormalized bending stiffness
      of an amphiphile mixture membrane tube in contact with a flat reservoir to be a
      quadratic function of curvature. In this analytical model, the degree of sorting
      is determined by the ratio of two thermodynamic derivatives. These derivatives
      are individually interpreted as a driving force and a resistance to curvature
      sorting. We experimentally show this ratio to vary with composition, and compare
      the model to sorting by spontaneous curvature. Our results are likely to be
      relevant to the molecular sorting of membrane components in vivo.

PMID- 19751669
TI  - Rapid actin-dependent viral motility in live cells.
AB  - During the course of an infection, viruses take advantage of a variety of
      mechanisms to travel in cells, ranging from diffusion within the cytosol to
      active transport along cytoskeletal filaments. To study viral motility within the
      intrinsically heterogeneous environment of the cell, we have developed a motility
      assay that allows for the global and unbiased analysis of tens of thousands of
      virus trajectories in live cells. Using this assay, we discovered that poliovirus
      exhibits anomalously rapid intracellular movement that was independent of
      microtubules, a common track for fast and directed cargo transport. Such rapid
      motion, with speeds of up to 5 microm/s, allows the virus particles to quickly
      explore all regions of the cell with the exception of the nucleus. The rapid,
      microtubule-independent movement of poliovirus was observed in multiple human
      derived cell lines, but appeared to be cargo-specific. Other cargo, including a
      closely related picornavirus, did not exhibit similar motility. Furthermore, the
      motility is energy-dependent and requires an intact actin cytoskeleton,
      suggesting an active transport mechanism. The speed of this microtubule
      independent but actin-dependent movement is nearly an order of magnitude faster
      than the fastest speeds reported for actin-dependent transport in animal cells,
      either by actin polymerization or by myosin motor proteins.

PMID- 19751670
TI  - Ratchetlike properties of in vitro microtubule translocation by a Chlamydomonas
      inner-arm dynein species c in the presence of flow.
AB  - To investigate the force generation properties of Chlamydomonas axonemal inner
      arm dyneins in response to external force, we analyzed microtubule gliding on
      dynein-coated surfaces under shear flow. When inner-arm dynein c was used,
      microtubule translocation in the downstream direction accelerated with increasing
      flow speed in a manner that depended on the dynein density and ATP concentration.
      In contrast, the microtubule translocation velocity in the upstream direction was
      unaffected by the flow speed. The number of microtubules on the glass surface was
      almost constant with and without flow, suggesting that gliding acceleration was
      not simply caused by weakened dynein-microtubule binding. With other inner-arm
      dynein species, the microtubule gliding velocity was unaffected by the flow
      regardless of the flow direction or nucleotide concentration. The flow-generated
      force acting on a single dynein was estimated to be as small as approximately
      0.03 pN/dynein. These results indicate that dynein c possesses a ratchetlike
      property that allows acceleration only in one direction by a very small external
      force. This property should be important for slow- and fast-moving dyneins to
      function simultaneously within the axoneme.

PMID- 19751671
TI  - On the origin of kinesin limping.
AB  - Kinesin is a dimeric motor with twin catalytic heads joined to a common stalk.
      Kinesin molecules move processively along microtubules in a hand-over-hand walk,
      with the two heads advancing alternately. Recombinant kinesin constructs with
      short stalks have been found to "limp", i.e., exhibit alternation in the dwell
      times of successive steps. Limping behavior implies that the molecular
      rearrangements underlying even- and odd-numbered steps must differ, but the
      mechanism by which such rearrangements lead to limping remains unsolved. Here, we
      used an optical force clamp to measure individual, recombinant dimers and test
      candidate explanations for limping. Introducing a covalent cross-link into the
      stalk region near the heads had no effect on limping, ruling out possible stalk
      misregistration during coiled-coil formation as a cause. Limping was equally
      unaffected by mutations that produced 50-fold changes in stalk stiffness, ruling
      out models where limping arises from an asymmetry in torsional strain. However,
      limping was enhanced by perturbations that increased the vertical component of
      load on the motor, including increases in bead size or net load, and decreases in
      the stalk length. These results suggest that kinesin heads take different
      vertical trajectories during alternate steps, and that the rates for these
      motions are differentially sensitive to load.

PMID- 19751672
TI  - Force and premature binding of ADP can regulate the processivity of individual
      Eg5 dimers.
AB  - Using a high-resolution optical trapping instrument, we directly observed the
      processive motions of individual Eg5 dimers over a range of external loads and
      ATP, ADP, and phosphate concentrations. To constrain possible models for
      dissociation from the microtubule, we measured Eg5 run lengths and also compared
      the duration of the last step of a processive run to all previous step durations.
      We found that the application of large longitudinal forces in either hindering or
      assisting directions could induce Eg5-microtubule dissociation. At a constant
      moderate force, maintained with a force clamp, the premature binding of ADP
      strongly promoted microtubule release by Eg5, whereas the addition of ATP or
      phosphate had little effect on dissociation. These results imply that run length
      is determined not only by the load, but also by the concentration and type of
      nucleotides present, and therefore that the biochemical cycles of the two motor
      domains of the Eg5 dimer are coordinated to promote processive stepping.

PMID- 19751673
TI  - Conformational transition of giant DNA in a confined space surrounded by a
      phospholipid membrane.
AB  - It has been established that a long DNA molecule exhibits a large discrete
      conformational change from a coiled state to a highly folded state in aqueous
      solution, depending on the presence of various condensing agents such as
      polyamines. In this study, T4 DNA labeled with fluorescent dyes was encapsulated
      in a cell-sized microdroplet covered with a phospholipid membrane to investigate
      the conformational behavior of a DNA molecule in such a confined space.
      Fluorescence microscopy showed that the presence of Mg(2+) induced the adsorption
      of DNA onto the membrane inner-surface of a droplet composed of
      phosphatidylethanolamine, while no adsorption was observed onto a
      phosphatidylcholine membrane. Under the presence of spermine (tetravalent amine),
      DNA had a folded conformation in the bulk solution. However, when these molecules
      were encapsulated in the microdroplet, DNA adsorbed onto the membrane surface
      accompanied by unfolding of its structure into an extended coil conformation
      under high concentrations of Mg(2+). In addition, DNA molecules trapped in large
      droplets tended not to be adsorbed on the membrane, i.e., no conformational
      transition occurred. A thermodynamic analysis suggests that the translational
      entropy loss of a DNA molecule that is accompanied by adsorption is a key factor
      in these phenomena under micrometer-scale confinement.

PMID- 19751674
TI  - The effect of different force applications on the protein-protein complex Barnase
      Barstar.
AB  - Steered molecular dynamics simulations are a tool to examine the energy landscape
      of protein-protein complexes by applying external forces. Here, we analyze the
      influence of the velocity and geometry of the probing forces on a protein complex
      using this tool. With steered molecular dynamics, we probe the stability of the
      protein-protein complex Barnase-Barstar. The individual proteins are mechanically
      labile. The Barnase-Barstar binding site is more stable than the folds of the
      individual proteins. By using different force protocols, we observe a variety of
      responses of the system to the applied tension.

PMID- 19751675
TI  - The structure of neuroglobin at high Xe and Kr pressure reveals partial
      conservation of globin internal cavities.
AB  - Neuroglobin (Ngb) is a hexacoordinate globin expressed in the brain of
      vertebrates. Ferrous Ngb binds dioxygen with high affinity and the O(2) adduct is
      able to scavenge NO. Convincing in vitro and in vivo data indicate that Ngb is
      involved in neuroprotection during hypoxia and ischemia. The 3D structure of Ngb
      reveals the presence of a wide internal cavity connecting its heme active site
      with the bulk. To explore the role of this "tunnel" in the control of ligand
      binding, we determined the structure of metNgb and NgbCO equilibrated with Xe or
      Kr. We show four docking sites for Xe (only two for Kr); two of the four Xe sites
      are within the large cavity. They are only partially conserved in globins, since
      the two proximal Xe sites identified in myoglobin (Xe1 and Xe2) are absent in
      Ngb, as well as in cytoglobin. The Xe docking sites in Ngb map a pathway within
      the protein matrix, leading to the heme, which becomes more accessible in the
      ligand-bound species. This may be of significance in connection with the redox
      chemistry that may be the primary function of this hexacoordinate globin.

PMID- 19751676
TI  - Structural changes to monomeric CuZn superoxide dismutase caused by the familial
      amyotrophic lateral sclerosis-associated mutation A4V.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron degenerative
      disease, and the inherited form, familial ALS (fALS), has been linked to over 100
      different point mutations scattered throughout the Cu-Zn superoxide dismutase
      protein (SOD1). The disease is likely due to a toxic gain of function caused by
      the misfolding, oligomerization, and eventual aggregation of mutant SOD1, but it
      is not yet understood how the structurally diverse mutations result in a common
      disease phenotype. The behavior of the apo-monomer fALS-associated mutant protein
      A4V was explored using molecular-dynamics simulations to elucidate characteristic
      structural changes to the protein that may allow the mutant form to improperly
      associate with other monomer subunits. Simulations showed that the mutant protein
      is less stable than the WT protein overall, with shifts in residue-residue
      contacts that lead to destabilization of the dimer and metal-binding sites, and
      stabilization of nonnative contacts that leads to a misfolded state. These
      findings provide a unifying explanation for disparate experimental observations,
      allow a better understanding of alterations of residue contacts that accompany
      loss of SOD1 structural integrity, and suggest sites where compensatory changes
      may stabilize the mutant structure.

PMID- 19751677
TI  - Coupling of pressure-induced structural shifts to spectral changes in a yellow
      fluorescent protein.
AB  - X-ray diffraction analysis of pressure-induced structural changes in the Aequorea
      yellow fluorescent protein Citrine reveals the structural basis for the
      continuous fluorescence peak shift from yellow to green that is observed on
      pressurization. This fluorescence peak shift is caused by a reorientation of the
      two elements of the Citrine chromophore. This study describes the structural
      linkages in Citrine that are responsible for the local reorientation of the
      chromophore. The deformation of the Citrine chromophore is actuated by the
      differential motion of two clusters of atoms that compose the beta-barrel
      scaffold of the molecule, resulting in a slight bending of the beta-barrel. The
      high-pressure structures also show a perturbation of the hydrogen bonding network
      that stabilizes the excited state of the Citrine chromophore. The perturbation of
      this network is implicated in the reduction of fluorescence intensity of Citrine.
      The blue-shift of the Citrine fluorescence spectrum resulting from the bending of
      the beta-barrel provides structural insight into the transient blue-shifting of
      isolated yellow fluorescent protein molecules under ambient conditions and
      suggests mechanisms to alter the time-dependent behavior of Citrine under ambient
      conditions.

PMID- 19751678
TI  - Selecting high quality protein structures from diverse conformational ensembles.
AB  - Protein structure prediction encompasses two major challenges: 1), the generation
      of a large ensemble of high resolution structures for a given amino-acid
      sequence; and 2), the identification of the structure closest to the native
      structure for a blind prediction. In this article, we address the second
      challenge, by proposing what is, to our knowledge, a novel iterative traveling
      salesman problem-based clustering method to identify the structures of a protein,
      in a given ensemble, which are closest to the native structure. The method
      consists of an iterative procedure, which aims at eliminating clusters of
      structures at each iteration, which are unlikely to be of similar fold to the
      native, based on a statistical analysis of cluster density and average spherical
      radius. The method, denoted as ICON, has been tested on four data sets: 1), 1400
      proteins with high resolution decoys; 2), medium-to-low resolution decoys from
      Decoys 'R' Us; 3), medium-to-low resolution decoys from the first-principles
      approach, ASTRO-FOLD; and 4), selected targets from CASP8. The extensive tests
      demonstrate that ICON can identify high-quality structures in each ensemble,
      regardless of the resolution of conformers. In a total of 1454 proteins, with an
      average of 1051 conformers per protein, the conformers selected by ICON are, on
      an average, in the top 3.5% of the conformers in the ensemble.

PMID- 19751679
TI  - How does a simplified-sequence protein fold?
AB  - To investigate a putatively primordial protein we have simplified the sequence of
      a 56-residue alpha/beta fold (the immunoglobulin-binding domain of protein G) by
      replacing it with polyalanine, polythreonine, and diglycine segments at regions
      of the sequence that in the folded structure are alpha-helical, beta-strand, and
      turns, respectively. Remarkably, multiple folding and unfolding events are
      observed in a 15-micros molecular dynamics simulation at 330 K. The most stable
      state (populated at approximately 20%) of the simplified-sequence variant of
      protein G has the same alpha/beta topology as the wild-type but shows the
      characteristics of a molten globule, i.e., loose contacts among side chains and
      lack of a specific hydrophobic core. The unfolded state is heterogeneous and
      includes a variety of alpha/beta topologies but also fully alpha-helical and
      fully beta-sheet structures. Transitions within the denatured state are very
      fast, and the molten-globule state is reached in <1 micros by a framework
      mechanism of folding with multiple pathways. The native structure of the wild
      type is more rigid than the molten-globule conformation of the simplified
      sequence variant. The difference in structural stability and the very fast
      folding of the simplified protein suggest that evolution has enriched the
      primordial alphabet of amino acids mainly to optimize protein function by
      stabilization of a unique structure with specific tertiary interactions.

PMID- 19751680
TI  - Extracting the causality of correlated motions from molecular dynamics
      simulations.
AB  - The information theory measure of transfer entropy is used to extract the
      causality of correlated motions from molecular dynamics simulations. For each
      pair of correlated residues, the method quantifies which residue drives the
      correlated motions, and which residue responds. The measure reveals how
      correlated motions are used to transmit information through the system, and helps
      to clarify the link between correlated motions and biological function in
      biomolecular systems. The method is illustrated by its application to the Ets-1
      transcription factor, which partially unfolds upon binding DNA. The calculations
      show dramatic changes in the direction of information flow upon DNA binding, and
      elucidate how the presence of DNA is communicated from the DNA binding H1 and H3
      helices to inhibitory helix HI-1. Helix H4 is shown to act as a relay, which is
      attenuated in the apo state.

PMID- 19751681
TI  - Changes in electrostatic surface potential of Na+/K+-ATPase cytoplasmic headpiece
      induced by cytoplasmic ligand(s) binding.
AB  - A set of single-tryptophan mutants of the Na(+)/K(+)-ATPase isolated, large
      cytoplasmic loop connecting transmembrane helices M4 and M5 (C45) was prepared to
      monitor effects of the natural cytoplasmic ligands (i.e., Mg(2+) and/or ATP)
      binding. We introduced a novel method for the monitoring of the changes in the
      electrostatic surface potential (ESP) induced by ligand binding, using the
      quenching of the intrinsic tryptophan fluorescence by acrylamide or iodide. This
      approach opens a new way to understanding the interactions within the proteins.
      Our experiments revealed that the C45 conformation in the presence of the ATP
      (without magnesium) substantially differed from the conformation in the presence
      of Mg(2+) or MgATP or in the absence of any ligand not only in the sense of
      geometry but also in the sense of the ESP. Notably, the set of ESP-sensitive
      residues was different from the set of geometry-sensitive residues. Moreover, our
      data indicate that the effect of the ligand binding is not restricted only to the
      close environment of the binding site and that the information is in fact
      transmitted also to the distal parts of the molecule. This property could be
      important for the communication between the cytoplasmic headpiece and the cation
      binding sites located within the transmembrane domain.

PMID- 19751682
TI  - Global and local mobility of apocalmodulin monitored through fast-field cycling
      relaxometry.
AB  - Calmodulin (CaM) is a ubiquitous eukaryotic protein with two conformationally
      independent domains that can bind up to two calcium ions each. In the calcium
      bound state, CaM is able to regulate a vast number of cellular activities by
      binding to a multiplicity of target proteins in different modes. Its versatility
      has been ascribed to its anomalously high flexibility. The calcium-free form
      (apoCaM), which is the resting state of CaM in cells, is also able to
      functionally bind a number of protein targets, but its dynamics has received less
      attention. At variance with the calcium-bound form, the crystal structure of
      apoCaM shows a compact organization of the two domains, but NMR measurements
      could not detect any contact between them, thus indicating the presence of
      mobility in solution. The mobility of apoCaM is here investigated through protein
      proton relaxation rate measurements performed with a high-sensitivity fast-field
      cycling relaxometer. Such measurements provide direct access to the spectral
      density function and show that 1), the reorientation time is in agreement with a
      closed form of the protein; but 2), the collective order parameter is much
      smaller than for other well folded compact proteins, indicating that a remarkably
      large side-chain mobility must be present.

PMID- 19751683
TI  - Direct observation of downhill folding of lambda-repressor in a microfluidic
      mixer.
AB  - The protein lambda(6-85) has been implicated in barrierless folding by
      observations of kinetic relaxation after nanosecond T-jump. In this work we
      observed folding of this protein after dilution of a high denaturant in an
      ultrarapid microfluidic mixer at temperatures far below the thermal midpoint. The
      observations of total intensity and spectral shift of tryptophan fluorescence
      yielded distinctly different kinetics and activation energies. These results may
      be explained as diffusion on a low-barrier, one-dimensional, free-energy surface,
      with different probes having different sensitivities along the reaction
      coordinate. Additionally, we observed an extremely fast phase within the mixing
      time that was not observed by T-jump, suggesting that the ensemble of unfolded
      states populated at high denaturant is distinct from those accessible at high
      temperature.

PMID- 19751684
TI  - Tryptophan conformations associated with partial unfolding in ribonuclease T1.
AB  - The origin of the biexponential fluorescence decay of Trp in ribonuclease T1
      under mildly destabilizing conditions, such as increased pH or temperature, or
      the presence of detergent, is still not understood. We have performed two
      extended replica-exchange molecular dynamics simulations to obtain a detailed
      representation of the native state at two protonation states corresponding to a
      high and low pH. At high pH, the appearance of partially unfolded states is
      evident. We found that this pH-induced destabilization originates from increased
      global repulsion as well as reduced local favorable electrostatic interactions
      and reduced H-bonding strength of His(27), His(40), and His(92). At high pH,
      alternative tryptophan rotamers appear and are linked to a distorted environment
      of the tryptophan, which also acts as a separate source of ground-state
      heterogeneity. The total population of these alternative conformations agrees
      well with the amplitude of the experimentally observed secondary fluorescence
      lifetime.

PMID- 19751685
TI  - Understanding protein structure from a percolation perspective.
AB  - Underlying the unique structures and diverse functions of proteins are a vast
      range of amino-acid sequences and a highly limited number of folds taken up by
      the polypeptide backbone. By investigating the role of noncovalent connections at
      the backbone level and at the detailed side-chain level, we show that these
      unique structures emerge from interplay between random and selected features.
      Primarily, the protein structure network formed by these connections shows simple
      (bond) and higher order (clique) percolation behavior distinctly reminiscent of
      random network models. However, the clique percolation specific to the side-chain
      interaction network bears signatures unique to proteins characterized by a larger
      degree of connectivity than in random networks. These studies reflect some
      salient features of the manner in which amino acid sequences select the unique
      structure of proteins from the pool of a limited number of available folds.

PMID- 19751686
TI  - Induced beta-barrel formation of the Alzheimer's Abeta25-35 oligomers on carbon
      nanotube surfaces: implication for amyloid fibril inhibition.
AB  - Recent experimental studies show that carbon nanotubes impact the aggregation
      process of proteins associated with neurodegenerative diseases. However, the
      details of molecular interactions between proteins and carbon nanotubes are still
      not well understood. In this study, we investigate the initial adsorption
      features and dynamics of the Alzheimer's amyloid-beta peptide spanning residues
      25-35 (Abeta25-35) on a single-walled carbon nanotube (SWNT) surface using fully
      atomic molecular dynamics simulations (MD) in explicit solvent. The initial
      configurations of the Abeta25-35 peptides consist of two preformed bilayer beta
      sheets, each with four or five beta-strands in parallel or mixed antiparallel
      parallel orientations. Our simulations show, for what we believe is the first
      time, that two disjointed Abeta25-35 beta-sheets with mixed antiparallel-parallel
      strands can assemble into beta-barrels wrapping the SWNT. In contrast, both
      simulations of Abeta25-35 without SWNT, and simulations of SWNT-Abeta25-35 with
      purely parallel beta-strands, lead to disordered aggregates. We find that Abeta25
      35 beta-barrel formation involves at least two steps: i), curving of the Abeta25
      35 beta-sheets as a result of strong hydrophobic interactions with carbon
      nanotube concomitantly with dehydration of the SWNT-peptide interface; and ii),
      intersheet backbone hydrogen bond formation with fluctuating intrasheet hydrogen
      bonds. Detailed analysis of the conversion shows that beta-barrel formation on
      SWNT surface results from the interplay of dehydration and peptide-SWNT/peptide
      peptide interactions. Implications of our results on amyloid fibril inhibition
      are discussed.

PMID- 19751687
TI  - Recognition imaging of acetylated chromatin using a DNA aptamer.
AB  - Histone acetylation plays an important role in the regulation of gene expression.
      A DNA aptamer generated by in vitro selection to be highly specific for histone
      H4 protein acetylated at lysine 16 was used as a recognition element for atomic
      force microscopy-based recognition imaging of synthetic nucleosomal arrays with
      precisely controlled acetylation. The aptamer proved to be reasonably specific at
      recognizing acetylated histones, with recognition efficiencies of 60% on-target
      and 12% off-target. Though this selectivity is much poorer than the >2000:1
      equilibrium specificity of the aptamer, it is a large improvement on the
      performance of a ChIP-quality antibody, which is not selective at all in this
      application, and it should permit high-fidelity recognition with repeated
      imaging. The ability to image the precise location of posttranslational
      modifications may permit nanometer-scale investigation of their effect on
      chromatin structure.

PMID- 19751688
TI  - Assessment of vaccine potential of the Neisseria-specific protein NMB0938.
AB  - The availability of complete genome sequence of Neisseria meningitidis serogroup
      B strain MC58 and reverse vaccinology has allowed the discovery of several novel
      antigens. Here, we have explored the potential of N. meningitidis lipoprotein
      NMB0938 as a vaccine candidate, based on investigation of gene sequence
      conservation and the antibody response elicited after immunization in mice. This
      antigen was previously identified by a genome-based approach as an outer membrane
      lipoprotein unique to the Neisseria genus. The nmb0938 gene was present in all 37
      Neisseria isolates analyzed in this study. Based on amino acid sequence identity,
      16 unique sequences were identified which clustered into three variants with
      identities ranging from 92 to 99%, with one cluster represented by the Neisseria
      lactamica strains. Recombinant protein NMB0938 (rNMB0938) was expressed in
      Escherichia coli and purified after solubilization of the insoluble fraction.
      Antisera produced in mice against purified rNMB0938 reacted with a range of
      meningococcal strains in whole-cell ELISA and western blotting. Using flow
      cytometry, it was also shown that anti-rNMB0938 antibodies bound to the surface
      of the homologous meningococcal strain and activated complement deposition.
      Moreover, antibodies against rNMB0938 elicited complement-mediated killing of
      meningococcal strains from both sequence variants and conferred passive
      protection against meningococcal bacteremia in infant rats. According to our
      results, NMB0938 represents a promising candidate to be included in a vaccine to
      prevent meningococcal disease.

PMID- 19751689
TI  - MF59-adjuvanted versus non-adjuvanted influenza vaccines: integrated analysis
      from a large safety database.
AB  - BACKGROUND: Adding adjuvants such as MF59((R)) to influenza vaccines can enhance
      the immune response. This analysis evaluated the safety profile of MF59
      adjuvanted [(+)MF59] compared with non-adjuvanted [(-)MF59] vaccines in a large
      clinical database. METHODS: Safety data were pooled from 64 clinical trials
      involving (+)MF59 seasonal and pandemic influenza vaccines. Safety outcomes were
      analysed in the overall population and in subjects aged > or =65 years, in all
      clinical trials and in controlled trials only. FINDINGS: Data from 20,447 (+)MF59
      and 7526 (-)MF59 subjects were analysed. Overall, (+)MF59 subjects had lower
      risks than (-)MF59 subjects of experiencing any unsolicited adverse event (AE)
      (26.8% vs 39.2%; adjusted risk ratio [ARR] 0.65; 95% CI 0.60-0.70),
      cardiovascular AEs (1.9% vs 5.6%; ARR 0.44; 95% CI 0.35-0.55), new onset chronic
      diseases (1.3% vs 1.9%; ARR 0.71; 95% CI 0.57-0.87) and death (0.8% vs 1.2%; ARR
      0.67; 95% CI 0.51-0.87). Few AEs of potential autoimmune origin were reported:
      0.71 and 0.67 per 1000 with (+)MF59 and (-)MF59, respectively. As expected,
      (+)MF59 subjects had a higher risk of solicited local or systemic reactions
      within 3 days of vaccination (58.5% vs 46.9%, weighted RR 1.34; 95% CI 1.28
      1.40). Safety outcomes were consistent between total and elderly populations, and
      between all trials and controlled trials, although statistical significance was
      lost for some of the outcomes in the subgroups. INTERPRETATION: This large-scale
      analysis supports the good safety profile of (+)MF59 seasonal and pandemic
      influenza vaccines and suggests a clinical benefit over (-)MF59 influenza
      vaccines.

PMID- 19751690
TI  - Phenotypic and functional characterization of T-cells and in vitro replication of
      FMDV serotypes in bovine lymphocytes.
AB  - Peripheral blood mononuclear cells (PBMCs) from unvaccinated and vaccinated
      bovine calves were employed to study the alteration of different T-cell
      subpopulations, functional competence and detection of foot-and-mouth disease
      virus (FMDV) at different hours post in vitro infection (hpi) with FMDV serotype
      either O or A or Asia1. The alteration in T-lymphocyte subpopulations was
      analyzed by flow cytometry analysis using T-cell subpopulation specific
      monoclonal antibodies at various hpi. All the three FMDV serotypes down-regulate
      boCD4(+) and boCD8(+) T-cells up to 48hpi whereas down-regulation of boWC1(+) T
      cells was observed up to 48hpi with FMDV serotype O only from unvaccinated
      calves. In contrast, lymphocytes from vaccinated animals demonstrated significant
      up-regulation of boCD4(+), boCD8(+) and boWC1(+) T-cells following exposure to
      FMDV serotype either O or A or Asia1. The lymphoproliferative test for functional
      competence of PBMCs using PHA or inactivated FMDV serotype either O or A or Asia1
      antigens, revealed that PHA driven lymphoproliferative response (LPR) was
      significantly suppressed at 24, 48 and 72hpi in unvaccinated animals. Homotypic
      as well as heterotypic FMDV antigen specific LPRs were suppressed in PBMCs of
      unvaccinated animals infected with FMDV serotype either O or A or Asia1 and
      stimulated with FMDV antigens. FMDV was demonstrated by reverse transcription
      polymerase chain reaction (RT-PCR) and 3A-non-structural protein (NSP) expression
      in PBMCs infected in vitro with FMDV serotype either O or A or Asia1 at different
      hpi. Using RT-PCR, the amplified product revealed 1D gene specific product of
      FMDV serotype O (1301bp) or A (866bp) or Asia1 (914bp) in lymphocytes of both
      unvaccinated and vaccinated calves at different hpi with FMDV serotype either O
      or A or Asia1, respectively. Likewise, the 3A-NSP mAb based flow cytometry
      revealed significant increase in 3A-NSP expression in lymphocytes of unvaccinated
      and vaccinated calves at different hpi with FMDV serotype either O or A or Asia1.
      In conclusion, the present study provides significant evidence that FMDV infects
      PBMCs in vitro and leads to transient immuno-suppression of boCD4(+) and boCD8(+)
      T-cells.

PMID- 19751691
TI  - Risk factors for onset of osteoarthritis of the knee in older adults: a
      systematic review and meta-analysis.
AB  - OBJECTIVE: Knee osteoarthritis (OA) is common in older adults. Determination of
      risk factors for onset of knee OA may help in its prevention. The objective of
      this systematic review, and meta-analysis, was to determine the current evidence
      on risk factors for knee OA. DESIGN: A systematic literature search was carried
      out for cohort and case-control studies evaluating the association of
      demographic, comorbid, and other patient-determined factors with onset of knee
      OA. A scoring tool was developed to assess the quality of studies. Heterogeneity
      of studies was examined. Where possible studies were pooled to give an overall
      estimate of the association of factors with onset of knee OA. RESULTS: Of the
      2233 studies screened, 85 were eventually included in the review. Study quality
      tended to be moderate. The main factors consistently associated with knee OA were
      obesity (pooled OR 2.63, 95% CI 2.28-3.05), previous knee trauma (pooled OR 3.86,
      95% CI 2.61-5.70), hand OA (pooled OR 1.49, 95% CI 1.05-2.10), female gender
      (pooled OR 1.84 95% CI 1.32-2.55) and older age. Smoking appeared to have a
      moderate protective effect, however this was not evident once the analysis was
      restricted to cohort studies only. CONCLUSIONS: Whilst certain factors have been
      extensively reviewed (for example, body mass index), more longitudinal studies
      are needed to investigate the association of physical occupational and other
      patient-determined factors with future knee OA. The quality of such studies also
      needs to be improved. However, there are identifiable factors which can be
      targeted for prevention of disabling knee pain.

PMID- 19751692
TI  - Assessment of strategies to increase chondrocyte viability in cryopreserved human
      osteochondral allografts: evaluation of the glycosylated hydroquinone, arbutin.
AB  - OBJECTIVE: Allogeneic cartilage is used to repair damaged areas of articular
      cartilage, requiring the presence of living chondrocytes. So far, no preservation
      method can effectively meet that purpose. Identification of more effective
      cryoprotective agents (CPAs) can contribute to this goal. The aim of this study
      was to determine whether the glycosylated hydroquinone, arbutin, alone or in
      combination with low concentrations of other CPAs, has cryoprotective properties
      towards human articular cartilage. MATERIAL AND METHODS: Human tibial plateaus
      were procured from multi-organ donors, with the approval of the Ethics Committee
      of the University Hospital of Coimbra. The tibial plateaus were treated with or
      without arbutin (50 or 100mM), alone or in combination with various
      concentrations of dimethyl sulfoxide (DMSO) and glycerol, for 0.5-1.5h/37 degrees
      C, then frozen at -20 degrees C and 24h later transferred to a biofreezer at -80
      degrees C. Two to 3 months later, thawing was achieved by immersion in cell
      culture medium at 37 degrees C/1h. Chondrocyte viability was assessed before and
      after freeze-thawing using a colorimetric assay based on the cell's metabolic
      activity and fluorescent dyes to evaluate cell membrane integrity. RESULTS:
      Before freezing, chondrocyte metabolic activity was identical in all the
      conditions tested. After freeze-thawing, the highest activity, corresponding to
      34.2+/-2.1% of that in the Fresh Control, was achieved in tibial plateaus
      incubated in 50mM arbutin for 1h whereas in those left untreated it was 11.1+/
      4.7. Addition of DMSO and glycerol to arbutin did not increase chondrocyte
      viability any further. Fluorescence microscopy confirmed these results and showed
      that living chondrocytes were mainly restricted to the superficial cartilage
      layers. CONCLUSION: Arbutin seems to be an effective cryoprotective agent for
      osteochondral allografts with potential benefits over DMSO and glycerol.

PMID- 19751693
TI  - Editorial.

PMID- 19751694
TI  - Microfluidic formation of single cell array for parallel analysis of Ca2+ release
      activated Ca2+ (CRAC) channel activation and inhibition.
AB  - High-throughput single cell analysis is required for understanding and predicting
      the complex stochastic responses of individual cells in changing environments. We
      have designed a microfluidic device consisting of parallel, independent channels
      with cell-docking structures for the formation of an array of individual cells.
      The microfluidic cell array was used to quantify single cell responses and the
      distribution of response patterns of calcium channels among a population of
      individual cells. In this device, 15 cell-docking units in each channel were
      fabricated with each unit containing 5 sandbag structures, such that an array of
      individual cells was formed in 8 independent channels. Single cell responses to
      different treatments in different channels were monitored in parallel to study
      the effects of the specific activator and inhibitor of the Ca(2+) release
      activated Ca(2+) (CRAC) channels. Multichannel detection was performed to obtain
      the response patterns of the population of cells within this single cell array.
      The results demonstrate that it is possible to acquire single cell features in
      multichannels simultaneously with passive structural control, which provides an
      opportunity for high-throughput single cell response analysis in a microfluidic
      chip.

PMID- 19751695
TI  - Selection of reference genes for real-time polymerase chain reaction analysis in
      tissues from Bombus terrestris and Bombus lucorum of different ages.
AB  - Quantitative real-time polymerase chain reaction (PCR) is an accurate and
      sensitive technique for gene expression analysis. However, it requires data
      normalization using reference genes. Here we assessed the stability of eight
      reference genes in the labial gland and fat body of the bumblebees Bombus
      terrestris and Bombus lucorum of different ages. To date, no reference genes have
      been identified for these species. Our data show that arginine kinase (AK) and
      phospholipase A2 (PLA2) are the most stable genes in both tissues of B.
      terrestris. The most stable genes for the labial gland and fat body of B. lucorum
      were found to be elongation factor 1alpha (EEF1A) and PLA2.

PMID- 19751696
TI  - Analysis of the effectiveness of reused primary and secondary antibodies in
      Western blotting analysis.
AB  - Western blot analysis is a common technique for detecting a target protein on a
      nitrocellulose membrane. The target protein is detected using specific
      antibodies. The positive signal can be visualized either by chemiluminescence or
      by a colorimetric reaction. Some specific antibodies can be produced in-house in
      high amounts and can be used without considering costs. However many antibodies
      (especially antibodies for detection tag fused proteins) must be purchased from a
      company. Unfortunately most of them are very expensive. Here we report the
      effectiveness of different antibodies after reusing them several times and also
      compare the influence of different storage conditions.

PMID- 19751697
TI  - Plate assay for fungal enzymes using cellophane membranes.
AB  - Fungal mycelia mass and pigments are major obstacles to investigating the
      secretion of bioactive substances such as enzyme activities using a plate assay.
      In this study, we applied a cellophane membrane and demonstrated that it can
      block mycelia mass and conidia (especially pigmented spores that would likely
      interfere with any subsequent color development-based activity detection) while
      allowing secreting enzymes to pass through. Visual observation after lifting the
      cellophane membrane and the collected mycelia and conidia indicated that the
      bioactivities on specific plates were improved significantly, although some
      fungal growth hurdle was noted. This proved to be true whether the assays were
      color development based or not.

PMID- 19751698
TI  - Determination of dansylated monoamine and amino acid neurotransmitters and their
      metabolites in human plasma by liquid chromatography-electrospray ionization
      tandem mass spectrometry.
AB  - The determination of neurotransmitters (NTs) and their metabolites facilitates
      better understanding of complex neurobiology in the central nervous system
      disorders and has expanding uses in many other fields. We present a liquid
      chromatography-electrospray ionization tandem mass spectrometry (LC-ESI/MS/MS)
      method for the quantification of dopamine (DA), 3,4-dihydroxyphenylacetic acid
      (DOPAC), homovanillic acid (HVA), norepinephrine (NE), vanillymandelic acid
      (VMA), 3-methoxy-4-hydroxy phenylglycol (MHPG), 5-hydroxytryptamine (5-HT), 5
      hydroxyindole-3-acetic acid (5-HIAA), glutamate (Glu), and gamma-aminobutyric
      acid (GABA). The NTs and their metabolites were dansylated and analyzed by an LC
      gradient on a C18 column on-line with a tandem mass spectrometer. This method
      exhibited excellent linearity for all of the analytes with regression
      coefficients higher than 0.99. The lower limit of quantification (LLOQ) values
      for DA, DOPAC, HVA, NE, VMA, MHPG, 5-HT, 5-HIAA, Glu, and GABA were 0.57, 0.37,
      0.35, 0.40, 0.35, 0.91, 0.27, 0.43, 0.65, and 1.62 pmol/ml, respectively. The
      precision results were expressed as coefficients of variation (CVs), ranging from
      1.5% to 13.6% for intraassay and from 2.9% to 13.7% for the interassay. This
      novel LC-ESI/MS/MS approach is precise, highly sensitive, specific, and
      sufficiently simple. It can provide an alternative method for the quantification
      of the NTs and their metabolites in human plasma.

PMID- 19751699
TI  - Assessment of synthetic chimeric multiple antigenic peptides for diagnosis of GB
      virus C infection.
AB  - The use of synthetic peptides of both structural and nonstructural proteins of GB
      virus C (GBV-C) has been studied for the development of new systems to diagnose
      infection caused by this virus. In an attempt to increase the antigenicity of
      linear peptide sequences, chimeric multiple antigenic peptides (MAPs) containing
      epitopes from E2, NS4, and NS5 GBV-C proteins have been synthesized. The
      synthetic constructs were evaluated by ELISA to establish whether the epitopes in
      chimeric branched peptides are more efficiently recognized by the specific
      antibodies compared to the monomeric linear sequences. Moreover, we have
      investigated the application of a commercial biosensor instrument for the
      detection of antibodies against the GBV-C in human serum samples. The results of
      the immunoassays reported in this work highlight the usefulness of synthetic
      tetrameric branched peptides containing sequences from envelope and nonstructural
      GBV-C proteins for the diagnosis of GBV-C infection. The potential clinical value
      of the MAP(4)(E2-NS5a) for the serodiagnosis of GBV-C infection was demonstrated,
      thus providing the basis for performing prevalence studies of the infection among
      the hemodialyzed and hepatitis C virus (HCV)-infected population.

PMID- 19751700
TI  - Purification and characterization of photosystem I complex from Synechocystis sp.
      PCC 6803 by expressing histidine-tagged subunits.
AB  - We generated Synechocystis sp. PCC 6803 strains, designated F-His and J-His,
      which express histidine-tagged PsaF and PsaJ subunits, respectively, for simple
      purification of the photosystem I (PSI) complex. Six histidine residues were
      genetically added to the C-terminus of the PsaF subunit in F-His cells and the N
      terminus of the PsaJ subunit in J-His cells. The histidine residues introduced
      had no apparent effect on photoautotrophic growth of the cells or the activity of
      PSI and PSII in thylakoid membranes. PSI complexes could be simply purified from
      the F-His and J-His cells by Ni2+-affinity column chromatography. When thylakoid
      membranes corresponding to 20 mg chlorophyll were used, PSI complexes
      corresponding to about 7 mg chlorophyll could be purified in both strains. The
      purified PSI complexes could be separated into monomers and trimers by
      ultracentrifugation in glycerol density gradient and high activity was recorded
      for trimers isolated from the F-His and J-His strains. Blue-Native PAGE and SDS
      PAGE analysis of monomers and trimers indicated the existence of two distinct
      monomers with different subunit compositions and no contamination of PSI with
      other complexes, such as PSII and Cyt b(6)f. Further analysis of proteins and
      lipids in the purified PSI indicated the presence of novel proteins in the
      monomers and about six lipid molecules per monomer unit in the trimers. These
      results demonstrate that active PSI complexes can be simply purified from the
      constructed strains and the strains are very useful tools for analysis of PSI.

PMID- 19751701
TI  - Alteration of mitochondrial oxidative phosphorylation in aged skeletal muscle
      involves modification of adenine nucleotide translocator.
AB  - The process of skeletal muscle aging is characterized by a progressive loss of
      muscle mass and functionality. The underlying mechanisms are highly complex and
      remain unclear. This study was designed to further investigate the consequences
      of aging on mitochondrial oxidative phosphorylation in rat gastrocnemius muscle,
      by comparing young (6 months) and aged (21 months) rats. Maximal oxidative
      phosphorylation capacity was clearly reduced in older rats, while mitochondrial
      efficiency was unaffected. Inner membrane properties were unaffected in aged rats
      since proton leak kinetics were identical to young rats. Application of top-down
      control analysis revealed a dysfunction of the phosphorylation module in older
      rats, responsible for a dysregulation of oxidative phosphorylation under low
      activities close to in vivo ATP turnover. This dysregulation is responsible for
      an impaired mitochondrial response toward changes in cellular ATP demand, leading
      to a decreased membrane potential which may in turn affect ROS production and ion
      homeostasis. Based on our data, we propose that modification of ANT properties
      with aging could partly explain these mitochondrial dysfunctions.

PMID- 19751702
TI  - The impact of window functions on NMR-based paramagnetic relaxation enhancement
      measurements in membrane proteins.
AB  - Though challenging, solution NMR spectroscopy allows fundamental interrogation of
      the structure and dynamics of membrane proteins. One major technical hurdle in
      studies of helical membrane proteins by NMR is the difficulty of obtaining
      sufficient long range NOEs to determine tertiary structure. For this reason, long
      range distance information is sometimes sought through measurement of
      paramagnetic relaxation enhancements (PRE) of NMR nuclei as a function of
      distance from an introduced paramagnetic probe. Current PRE interpretation is
      based on the assumption of Lorentzian resonance lineshapes. However, in order to
      optimize spectral resolution, modern multidimensional NMR spectra are almost
      always subjected to resolution-enhancement, leading to distortions in the
      Lorentizian peak shape. Here it is shown that when PREs are derived using peak
      intensities (i.e., peak height) and linewidths from both real and simulated
      spectra that were produced using a wide range of apodization/window functions,
      that there is little variation in the distances determined (<1 A at the
      extremes). This indicates that the high degree of resolution enhancement required
      to obtain well-resolved spectra from helical membrane proteins is compatible with
      the use of PRE data as a source of distance restraints. While these conclusions
      are particularly important for helical membrane proteins, they are generally
      applicable to all PRE measurements made using resolution-enhanced data.

PMID- 19751703
TI  - Preferential increase in the hippocampal synaptic vesicle protein 2A (SV2A) by
      pentylenetetrazole kindling.
AB  - The present study evaluated the expressional levels of synaptic vesicle protein
      2A (SV2A) and other secretary machinery proteins (i.e., soluble N-ethylmaleimide
      sensitive factor attachment protein receptor (SNARE) complexes, Munc18-1, N
      ethylmaleimide-sensitive factor (NSF) and soluble N-ethylmaleimide-sensitive
      factor attachment protein (SNAP)) in a pentylenetetrazole (PTZ) kindling model.
      Repeated administration of sub-convulsive PTZ (40 mg/kg, i.p.) progressively
      increased seizure susceptibility in mice and consistently induced clonic seizures
      in most animals tested at 15 days after the treatment. Western blot analysis
      revealed that, among the secretary machinery proteins examined, hippocampal SV2A
      was selectively elevated by PTZ kindling. PTZ kindling-induced SV2A expression
      appeared region-specific and the SV2A levels in the cerebral cortex or cerebellum
      were unaltered. In addition, SV2A expression by PTZ kindling was prominent in the
      hilar region of the dentate gyrus (DG) where GABAergic interneurons are located,
      but not in other hippocampal regions (e.g., the stratum lucidum of the CA3 and
      synaptic layers surrounding CA1 or CA3 pyramidal neurons). These findings suggest
      that PTZ kindling preferentially elevates SV2A expression in the hippocampus
      probably as a compensatory mechanism to activate the inhibitory
      neurotransmission.

PMID- 19751704
TI  - Primary cortical brain cells influence osteoblast activity.
AB  - The presence of neuropeptides and neuroreceptors in the bone have been reported
      in several studies. Bone turn-over seems to be controlled by the nervous system.
      The actual pathway or the control mechanism is still under investigation. In this
      study we investigate the changes in osteoblast cells if they are in co-culture
      with primary cortical brain cells. After seven days in co-culture with the
      primary fetal brain cells the osteoblast cells exhibited hypertrophic
      morphological changes and showed stronger ALP activity.

PMID- 19751705
TI  - Interaction of Hsp70 with p49/STRAP, a serum response factor binding protein.
AB  - Members of the Hsp70 protein family must work with other co-chaperones to exert
      their function. Herein, we identified a new Hsp70 co-chaperone, p49/STRAP,
      previously shown to interact with serum response factor. We demonstrated that a
      fraction of p49/STRAP was cytosolic, and that it interacted with the beta
      sandwich domain of Hsp70. Although p49/STRAP had little effect on the intrinsic
      ATPase activity of Hsp70, it reduced the ATP-hydrolytic activity of Hsp70
      stimulated by Hsp40, and inhibited the refolding activity of the Hsp70/Hsp40
      system. Thus, p49/STRAP can be considered a bona fide co-chaperone of Hsp70.

PMID- 19751706
TI  - Increased tolerance of rice to cold, drought and oxidative stresses mediated by
      the overexpression of a gene that encodes the zinc finger protein ZFP245.
AB  - ZFP245 is a cold- and drought-responsive gene that encodes a zinc finger protein
      in rice. The ZFP245 protein localizes in the nucleus and exhibits trans
      activation activity. Transgenic rice plants overexpressing ZFP245 were generated
      and found to display high tolerance to cold and drought stresses. The transgenic
      plants did not exhibit growth retardation, but showed growth sensitivity against
      exogenous abscisic acid, increased free proline levels and elevated expression of
      rice pyrroline-5-carboxylatesynthetase and proline transporter genes under stress
      conditions. Overproduction of ZFP245 enhanced the activities of reactive oxygen
      species-scavenging enzymes under stress conditions and increased the tolerance of
      rice seedlings to oxidative stress. Our data suggest that ZFP245 may contribute
      to the tolerance of rice plants to cold and drought stresses by regulating
      proline levels and reactive oxygen species-scavenging activities, and therefore
      may be useful for developing transgenic crops with enhanced tolerance to abiotic
      stress.

PMID- 19751707
TI  - Apoptotic effects of mahanine on human leukemic cells are mediated through
      crosstalk between Apo-1/Fas signaling and the Bid protein and via mitochondrial
      pathways.
AB  - Apo-1 (Fas/CD95), a cell surface receptor, triggers apoptosis after binding to
      its physiological ligand, Apo-1L (FasL/CD95L). This study reports that mahanine,
      purified from the leaves of Murraya koenigii, has a dose- and time-dependent anti
      proliferative activity in acute lymphoid (MOLT-3) and chronic myeloid (K562)
      leukemic cell lines and in the primary cells of leukemic and myeloid patients,
      with minimal effect on normal immune cells including CD34(+) cells. Leukemic
      cells underwent phosphatidylserine externalization and DNA fragmentation,
      indicating mahanine-induced apoptosis. An increase in reactive oxygen species
      suggests that the mahanine-induced apoptosis was mediated by oxidative stress. A
      significant drop in the Bcl2/Bax ratio, the loss of mitochondrial transmembrane
      potential as well as cytochrome c release from the mitochondria to the cytosol
      suggested involvement of the mitochondrial pathway of apoptosis. Cytochrome c
      release was followed by the activation of caspase-9, caspase-3 and caspase-7, and
      cleavage of PARP in both MOLT-3 and K562 cells. In MOLT-3 cells, formation of the
      Fas-FasL-FADD-caspase-8 heterotetramer occurred, leading to the cleavage of Bid
      to its truncated form, which consequently resulted in formation of the
      mitochondrial transmembrane pore. The incubation of MOLT-3 cells with mahanine in
      the presence of caspase-8 inhibitor or FasL-neutralizing NOK-2 antibody resulted
      in the decrease of mahanine-induced cell death. Mahanine was also a potent
      inhibitor of K562 xenograft growth, which was evident in an athymic nude mice
      model. In summary, these results provide evidence for involvement of the death
      receptor-mediated extrinsic pathway of apoptosis in the mahanine-induced
      anticancer activity in MOLT-3 cells, but not in K562 cells, which are deficient
      in Fas/FasL.

PMID- 19751708
TI  - Formic acid is essential for immunohistochemical detection of aggregated
      intraneuronal Abeta peptides in mouse models of Alzheimer's disease.
AB  - The staining protocols so far applied to study intracellular Abeta accumulation
      in human tissue have been inconsistent with varying use of heat and formic acid
      (FA) for antigen retrieval. Microwave heat treatment has been reported to enhance
      the staining of intraneuronal Abeta as compared to no or enzymatic pretreatment.
      FA is widely used to increase the staining of plaque pathology in AD, yet the
      effect of FA on intraneuronal Abeta staining has been reported to be low and
      similar to the effect of heat or even to counteract the enhancing effect of heat
      pretreatment on intraneuronal Abeta immunohistochemical detection. To overcome
      these inconsistencies, there is a need for optimization of the staining protocol
      for intraneuronal Abeta detection and more knowledge is required concerning the
      effects of the different antigen retrieval methods. In the present work, we
      optimized the staining protocol for intraneuronal Abeta in paraffin-embedded
      sections in relation to heat and FA using four different mouse models known to
      accumulate intraneuronal Abeta peptides. It was found that FA is essential for
      the staining of highly aggregated intraneuronal Abeta peptides in AD transgenic
      mouse tissue.

PMID- 19751709
TI  - Non-dioxin-like-PCBs phosphorylate Mdm2 at Ser166 and attenuate the p53 response
      in HepG2 cells.
AB  - Polychlorinated biphenyls (PCBs) are ubiquitous and persistent environmental
      pollutants that accumulated in the food chain. Traditionally they are divided
      into dioxin-like (DL)- and non-dioxin-like (NDL)-PCBs. NDL-PCBs have been shown
      to have tumor promotive activity in mice and co-carcinogenic effects in rats.
      However the mechanisms are poorly understood, hampering the risk assessment of
      NDL-PCBs. We have previously shown that TCDD attenuates p53 response by
      phosphorylating its regulator Mdm2 at Ser166, and that Erk can mediate this
      effect in hepatocytes. In this study we investigated the effects of 20 NDL-PCBs
      (concentration range 0.01-10microM) on pMdm2 Ser166, pErk Tyr204 and p53 on HepG2
      cells. Six of the NDL-PCBs induced pErk Tyr204 and pMdm3 Ser166. This effect
      correlated with lowered basal levels of p53, as well as with an attenuated p53
      response induced by etoposide and leptomycin B. Similar effects were induced by
      TCDD and the DL-PCB 126. We conclude that both DL-PCBs and NDL-PCBs in low
      concentrations can induce alterations in p53 signaling and that these effects can
      be correlated to rat liver carcinogenesis.

PMID- 19751710
TI  - Differential reactivities of four homogeneous assays for LDL-cholesterol in serum
      to intermediate-density lipoproteins and small dense LDL: comparisons with the
      Friedewald equation.
AB  - BACKGROUND: In routine clinical laboratory testing and numerous epidemiological
      studies, LDL-cholesterol (LDL-C) has been estimated commonly using the Friedewald
      equation. We investigated the relationship between the Friedewald equation and 4
      homogeneous assays for LDL-C. METHODS: LDL-C was determined by 4 homogeneous
      assays [liquid selective detergent method: LDL-C (L), selective solubilization
      method: LDL-C (S), elimination method: LDL-C (E), and enzyme selective protecting
      method: LDL-C (P)]. Samples with discrepancies between the Friedewald equation
      and the 4 homogeneous assays for LDL-C were subjected to polyacrylamide gel
      electrophoresis and the beta-quantification method. RESULTS: The correlations
      between the Friedewald equation and the 4 homogeneous LDL-C assays were as
      follows: LDL-C (L) (r=0.962), LDL-C (S) (r=0.986), LDL-C (E) (r=0.946) and LDL-C
      (P) (r=0.963). Discrepancies were observed in sera from type III
      hyperlipoproteinemia patients and in sera containing large amounts of midband and
      small dense LDL on polyacrylamide gel electrophoresis. LDL-C (S) was most
      strongly correlated with the beta-quantification method even in sera from
      patients with type III hyperlipoproteinemia. CONCLUSIONS: Of the 4 homogeneous
      assays for LDL-C, LDL-C (S) exhibited the closest correlation with the Friedewald
      equation and the beta-quantification method, thus reflecting the current clinical
      databases for coronary heart disease.

PMID- 19751711
TI  - Autoantibodies against phosphatidylserine, prothrombin and phosphatidylserine
      prothrombin complex: identical or distinct diagnostic tools for antiphospholipid
      syndrome?
AB  - BACKGROUND: To clarify the association and diagnostic utility of measuring
      antiphosphatidyl serine (aPS), antiprothrombin (aPT) and the antiphosphatidyl
      serine/prothrombin complex (aPS/PT) antibodies in patients with antiphospholipid
      syndrome (APS) and recurrent pregnancy loss (RPL). METHOD: We measured IgG and
      IgM anti-aPS/PT (2 different kits) as well as the aPS and aPT autoantibodies by
      ELISA. All subjects were also tested for the presence of Lupus anticoagulant
      (LA), IgG and IgM anti-cardiolipin (aCL) and anti-beta-2 glycoprotein I
      (ass(2)GPI), and these served as the gold standard unless otherwise indicated.
      Two groups of patients were studied: (i) APS with RPL and/or thrombosis (n=62);
      (ii) RPL only (n=66) and a group of healthy women with successful pregnancies
      (WSP; n=30). RESULTS: The area under curve (AUC) analyses demonstrated
      significant differences between the aPS/PT (0.980) and aPT (0.850) assays
      (p=0.002) with no significant differences between the 2 aPS/PT kits or the aPS/PT
      and aPS assays. The overall agreement between the tested aPL antibodies and lupus
      anticoagulant (LA) for the APS cohort was very poor but associations between aPL
      assays were substantial (kappa>0.5) as determined by Cohen kappa analysis.
      CONCLUSIONS: Our data show a lack of association between aPS/PT antibodies and LA
      in APS patients with recurrent pregnancy loss. In the evaluation of these
      patients, there may be redundancy in testing all three markers as the aPT and aPS
      assays formed part of the aPS/PT antibody repertoire.

PMID- 19751712
TI  - Phenotypic and genotypic characterization of Factor VII deficiency patients from
      Western India.
AB  - BACKGROUND: Congenital factor VII (FVII) deficiency is a rare coagulation
      deficiency caused due to defects in the FVII gene. METHODS: We analyzed 14
      unrelated Indian patients with congenital FVII deficiency for mutations in FVII
      gene by conformation sensitive gel electrophoresis (CSGE) followed by DNA
      sequencing. RESULTS: A total of 11 different missense mutations were identified,
      of which 5 were novel (Ala191Pro, Asp338Glu, Ile138Thr, Leu263Arg and Trp284Arg)
      and 6 had been previously reported (Cys22Arg, Arg152Gln, Cys310Phe, Thr324Met,
      Gly117Arg and His348Arg). Six of the 11 mutations were located in the catalytic
      serine protease domain, 3 in the activation domain and 1 each in the Gla and the
      second epidermal growth factor domain respectively. Multiple sequence alignment
      using ClustalW2 analysis showed that all the mutations were found in residues
      that are highly conserved across species. Implications of mutations on the
      structural stability and function of human factor VIII (hFVII) using Swiss-Pdb
      Viewer and the intra-molecular interactions of the mutant residues using PIC
      showed that there is a structural instability in all the mutants either by steric
      hindrance or instability in the protein molecule folding. CONCLUSION: A wide
      spectrum of mutations was detected in the FVII gene; the presence of 6 out of 11
      mutations in the serine protease domain suggests the crucial role of catalytic
      domain in FVII functional activity.

PMID- 19751713
TI  - Circulating cell-free DNA levels in plasma increase with severity in experimental
      acute pulmonary thromboembolism.
AB  - BACKGROUND: The diagnosis of acute pulmonary thromboembolism (APT) and its
      severity is challenging. No previous study has examined whether there is a linear
      relation between plasma DNA concentrations and the severity of APT. We examined
      this hypothesis in anesthetized dogs. We also examined the changes in plasma DNA
      concentrations in microspheres lung embolization and whether the therapy of APT
      with nitrite could modify APT-induced changes in plasma DNA concentrations. In
      vitro DNA release from blood clots was also studied. METHODS: APT was induced
      with autologous blood clots (saline, 1, 3, or 5 ml/kg) injected into the right
      atrium. A group of dogs received 300 microm microspheres into the inferior vena
      cava to produce similar pulmonary hypertension. Another group of dogs received
      6.75 micromol/kg nitrite after APT with blood clots of 5 ml/kg. Hemodynamic
      evaluations were carried out for 120 min. DNA was extracted from plasma samples
      using QIAamp DNA Blood Mini Kit and quantified using Quant-iT PicoGreen dsDNA
      detection kit at baseline and 120 min after APT. RESULTS: APT produced dose
      dependent increases in plasma DNA concentrations, which correlated positively
      with pulmonary vascular resistance (P=0.002, r=0.897) and with mean pulmonary
      arterial pressure (P=0.006, r=0.856). Conversely, lung embolization with
      microspheres produced no significant changes in plasma DNA concentrations. While
      nitrite attenuated APT-induced pulmonary hypertension, it produced no changes in
      plasma DNA concentrations. Blood clots released dose-dependent amounts of DNA in
      vitro. CONCLUSIONS: Cell-free DNA concentrations increase in proportion to the
      severity of APT, probably as a result of increasing amounts of thrombi
      obstructing the pulmonary vessels.

PMID- 19751714
TI  - Analytical performance characteristics of the Abbott Architect i2000 Tacrolimus
      assay; comparisons with liquid chromatography-tandem mass spectrometry (LC-MS/MS)
      and Abbott IMx methods.
AB  - BACKGROUND: Tacrolimus, an immunosuppressive drug discovered in 1984, is used to
      decrease the risk of organ rejection. The 2007 European Consensus Conference on
      Tacrolimus Optimization recommended the use of methods with a limit of
      quantitation at < or =1ng/ml for monitoring low dose tacrolimus therapy. METHODS:
      The performance characteristics of the Abbott i2000 Tacrolimus assay were
      evaluated and compared to LC-MS/MS and Abbott IMx methods. RESULTS: The limit of
      detection of the Abbott i2000 method was 0.21ng/ml. Total imprecision was 6.9,
      5.8 and 4.2% at three target concentrations of tacrolimus (3.2, 8.5 and
      15.9ng/ml) respectively. The method was linear up to 30ng/ml. The limit of
      quantitation (LOQ) was 0.5ng/ml. Correlation of patient specimen results between
      the Abbott i2000 method and LC-MS/MS yielded a Deming slope of 1.072ng/ml (CI
      1.005 to 1.140), r=0.952 and an intercept of -0.491ng/ml (CI -1.387 to 0.405).
      The mean bias, as determined by Bland-Altman analysis, was 0.36ng/ml. Comparing
      results generated by the widely used Abbott IMx assay with LC-MS/MS and Architect
      i2000 methods yielded Deming slopes of 1.062 and 0.973, with intercepts of 
      0.214ng/ml and -0.01ng/ml respectively. For both comparisons, r=0.97. The
      corresponding mean bias of results generated by the Abbott IMx assay (Bland
      Altman plots) was 0.53ng/ml vs LC-MS/MS and -0.38ng/ml vs the Architect i2000.
      CONCLUSIONS: The Architect i2000 method is a sensitive and highly precise method
      that achieves a LOQ of <1.0 ng/ml and demonstrated overall accuracy of tacrolimus
      measurements within 0.4ng/ml.

PMID- 19751715
TI  - A G560S mutation in alpha1 (I) collagen causes familial osteogenesis imperfecta
      type IV.

PMID- 19751716
TI  - Circulating matrix metalloproteinase-8 (MMP-8) and MMP-9 are increased in chronic
      periodontal disease and decrease after non-surgical periodontal therapy.
AB  - BACKGROUND: Periodontal disease shares risk factors with cardiovascular diseases
      and other systemic inflammatory diseases. The present study was designed to
      assess the circulating matrix metalloproteinases (MMPs) from chronic periodontal
      disease patients and, subsequently, after periodontal therapy. METHODS: We
      compared the plasma concentrations of MMP-2, MMP-3, MMP-8, MMP-9, tissue
      inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2, and total gelatinolytic
      activity in patients with periodontal disease (n=28) with those of control
      subjects (n=22) before and 3 months after non-surgical periodontal therapy.
      RESULTS: Higher plasma MMP-3, MMP-8, and MMP-9 concentrations were found in
      periodontal disease patients compared with healthy controls (all P<0.05), whereas
      MMP-2, TIMP-1, and TIMP-2 levels were not different. Treatment decreased plasma
      MMP-8 and MMP-9 concentrations by 35% and 39%, respectively (both P<0.02), while
      no changes were found in controls. MMP-2, MMP-3, TIMP-1, and TIMP-2 remained
      unaltered in both groups. Plasma gelatinolytic activity was higher in periodontal
      disease patients compared with controls (P<0.001) and decreased after periodontal
      therapy (P<0.05). CONCLUSIONS: This study showed increased circulating MMP-8 and
      MMP-9 levels and proteolytic activity in periodontal disease patients that
      decrease after periodontal therapy. The effects of periodontal therapy suggest
      that it may attenuate inflammatory chronic diseases.

PMID- 19751717
TI  - Enzyme-linked immunoabsorbent assay for detection of human serine protease corin
      in blood.
AB  - BACKGROUND: Corin is a tissue type II transmembrane protein that converts pro
      atrial natriuretic peptides and pro-brain natriuretic peptide to their active
      forms. Despite their protecting effect, high levels of these peptides indicate a
      bad prognosis. One of the possible explanations to this paradox is reduced
      cleavage due to low corin levels. The purpose of this study was to develop an
      assay to detect blood levels of corin. METHODS: ELISA was developed using rat
      monoclonal antibody to recombinant human corin as capture antibody, and
      biotinylated goat anti-human corin as detection antibody. RESULTS: Based on known
      corin concentration as standards, the ideal capture antibody concentration was
      500 ng/ml, and 200 ng/ml for detection antibody. The coefficient of variation was
      5.7% for inter-assay and 3.9% for intra-assay precision. Corin levels were stable
      when stored at room temperature for 1 day, for 3 days at 4 degrees C or up to 1
      year in -35 degrees C. Human serum corin levels were reproducibly measured in
      individuals and found to range from 296 to 2590 pg/ml. CONCLUSIONS: The
      immunoabsorbent assay developed in this study can accurately and reliably
      determine human serum corin levels, and is suitable for simple screening of corin
      in clinical practice.

PMID- 19751718
TI  - Characterization of the Caenorhabditis elegans UDP-galactopyranose mutase homolog
      glf-1 reveals an essential role for galactofuranose metabolism in nematode
      surface coat synthesis.
AB  - Galactofuranose (Gal(f)), the furanoic form of d-galactose produced by UDP
      galactopyranose mutases (UGMs), is present in surface glycans of some prokaryotes
      and lower eukaryotes. Absence of the Gal(f) biosynthetic pathway in vertebrates
      and its importance in several pathogens make UGMs attractive drug targets. Since
      the existence of Gal(f) in nematodes has not been established, we investigated
      the role of the Caenorhabditis elegans UGM homolog glf-1 in worm development. glf
      1 mutants display significant late embryonic and larval lethality, and other
      phenotypes indicative of defective surface coat synthesis, the glycan-rich
      outermost layer of the nematode cuticle. The glf homolog from the protozoan
      Leishmania major partially complements C. elegans glf-1. glf-1 mutants rescued by
      L. major glf, which behave as glf-1 hypomorphs, display resistance to infection
      by Microbacterium nematophilum, a pathogen of rhabditid nematodes thought to bind
      to surface coat glycans. To confirm the presence of Gal(f) in C. elegans, we
      analyzed C. elegans nucleotide sugar pools using online electrospray ionization
      mass spectrometry (ESI-MS). UDP-Gal(f) was detected in wild-type animals while
      absent in glf-1 deletion mutants. Our data indicate that Gal(f) likely has a
      pivotal role in maintenance of surface integrity in nematodes, supporting
      investigation of UGM as a drug target in parasitic species.

PMID- 19751719
TI  - Regulation of Drosophila matrix metalloprotease Mmp2 is essential for wing
      imaginal disc:trachea association and air sac tubulogenesis.
AB  - The Drosophila Dorsal Air Sac Primordium (ASP) is a tracheal tube that grows
      toward Branchless FGF-expressing cells in the wing imaginal disc. We show that
      the ASP arises from a tracheal branch that invades the basal lamina of the disc
      to juxtapose directly with disc cells. We examined the role of matrix
      metalloproteases (Mmps), and found that reducing Mmp2 activity perturbed disc
      trachea association, altered peritracheal distributions of collagen IV and
      Perlecan, misregulated ASP growth, and abrogated development of the dorsal air
      sacs. Whereas the function of the membrane-tethered Mmp2 in the ASP is non-cell
      autonomous we find that it may have distinct tissue-specific roles in the ASP and
      disc. These findings demonstrate a critical role for Mmp2 in tubulogenesis post
      induction, and implicate Mmp2 in regulating dynamic and essential changes to the
      extracellular matrix.

PMID- 19751720
TI  - Apical constriction: a cell shape change that can drive morphogenesis.
AB  - Biologists have long recognized that dramatic bending of a cell sheet may be
      driven by even modest shrinking of the apical sides of cells. Cell shape changes
      and tissue movements like these are at the core of many of the morphogenetic
      movements that shape animal form during development, driving processes such as
      gastrulation, tube formation, and neurulation. The mechanisms of such cell shape
      changes must integrate developmental patterning information in order to spatially
      and temporally control force production-issues that touch on fundamental aspects
      of both cell and developmental biology and on birth defects research. How does
      developmental patterning regulate force-producing mechanisms, and what roles do
      such mechanisms play in development? Work on apical constriction from multiple
      systems including Drosophila, Caenorhabditis elegans, sea urchin, Xenopus, chick,
      and mouse has begun to illuminate these issues. Here, we review this effort to
      explore the diversity of mechanisms of apical constriction, the diversity of
      roles that apical constriction plays in development, and the common themes that
      emerge from comparing systems.

PMID- 19751721
TI  - Isoform specificity of cardiac glycosides binding to human Na+,K+-ATPase
      alpha1beta1, alpha2beta1 and alpha3beta1.
AB  - Cardiac glycosides inhibit the Na(+),K(+)-ATPase and are used for the treatment
      of symptomatic heart failure and atrial fibrillation. In human heart three
      isoforms of Na(+),K(+)-ATPase are expressed: alpha(1)beta(1), alpha(2)beta(1) and
      alpha(3)beta(1). It is unknown, if clinically used cardiac glycosides differ in
      isoform specific affinities, and if the isoforms have specific subcellular
      localization in human cardiac myocytes. Human Na(+),K(+)-ATPase isoforms
      alpha(1)beta(1), alpha(2)beta(1) and alpha(3)beta(1) were expressed in yeast
      which has no endogenous Na(+),K(+)-ATPase. Isoform specific affinities of
      digoxin, digitoxin, beta-acetyldigoxin, methyldigoxin and ouabain were assessed
      in [(3)H]-ouabain binding assays in the absence or presence of K(+) (each n=5).
      The subcellular localizations of the Na(+),K(+)-ATPase isoforms were investigated
      in isolated human atrial cardiomyocytes by immunohistochemistry. In the absence
      of K(+), methyldigoxin (alpha(1)>alpha(3)>alpha(2)) and ouabain
      (alpha(1)=alpha(3)>alpha(2)) showed distinct isoform specific affinities, while
      for digoxin, digitoxin and beta-acetyldigoxin no differences were found. In the
      presence of K(+), also digoxin (alpha(2)=alpha(3)>alpha(1)) and beta
      acetyldigoxin (alpha(1)>alpha(3)) had isoform specificities. A comparison between
      the cardiac glycosides demonstrated highly different affinity profiles for the
      isoforms. Immunohistochemistry showed that all three isoforms are located in the
      plasma membrane and in intracellular membranes, but only alpha(1)beta(1) and
      alpha(2)beta(1) are located in the T-tubuli. Cardiac glycosides show distinct
      isoform specific affinities and different affinity profiles to Na(+),K(+)-ATPase
      isoforms which have different subcellular localizations in human cardiomyocytes.
      Thus, in contrast to current notion, different cardiac glycoside agents may
      significantly differ in their pharmacological profile which could be of hitherto
      unknown clinical relevance.

PMID- 19751722
TI  - The effects of NMDA receptor antagonists over intestinal ischemia/reperfusion
      injury in rats.
AB  - Intestinal ischemia/reperfusion causes severe injury and alters motility. N
      methyl-D-aspartate (NMDA) receptor antagonists have been shown to reduce
      ischemia/reperfusion injury in the nervous system, and in other organs. In this
      study, we set out to investigate the effects of NMDA receptor antagonists over
      intestinal ischemia/reperfusion injury. Male Wistar rats were randomly divided
      into four groups: (1) a control, sham-operated group; (2) an intestinal
      ischemia/reperfusion group subjected to 45 min ischemia and 1h reperfusion; (3) a
      group treated with 10 mg/kg ketamine before ischemia/reperfusion; and (4) a group
      treated with 10 mg/kg memantine before ischemia/reperfusion. Intestinal samples
      were taken for histological evaluation. Serum levels of aspartate
      aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase
      (LDH), malondialdehyde (MDA), total antioxidant capacity, tumor necrosis factor
      alpha (TNF-alpha), P-selectin and antithrombin III (ATIII) were measured.
      Intestinal transit time was determined to evaluate intestinal motility. Fecal
      pellet output and animal weight were also registered daily for 7 days post
      ischemia. After reperfusion, AST, LDH, TNF-alpha and P-selectin levels were
      elevated, ATIII levels were depleted, and ALT levels were unchanged in serum.
      Additionally, levels of MDA were increased and total antioxidant capacity was
      reduced in serum, indicating oxidative stress. Intestinal mucosa showed severe
      injury. Ketamine, but not memantine, diminished these alterations. Intestinal
      motility and fecal pellet output were also altered after ischemia/reperfusion.
      Both drugs abolished the alterations in motility. In conclusion, ketamine's
      protective effects over ischemia/reperfusion do not appear to be NMDA mediated,
      but they could be playing a role in protecting the intestine against ischemia
      induced functional changes.

PMID- 19751723
TI  - Identification, characterisation and regulation by CD40 activation of novel CD95
      splice variants in CD95-apoptosis-resistant, human, B-cell non-Hodgkin's
      lymphoma.
AB  - CD95 gene and splicing aberrations have been detected in B-cell non-Hodgkin
      lymphoma (B-NHL) where they are thought to contribute to CD95 apoptosis
      resistance. To further investigate this, we have performed extensive CD95
      transcript sequencing and functional analysis in B-NHL with demonstrated
      resistance to CD95-induced apoptosis (B-NHLr). Strikingly, instead of showing
      CD95 mutations per se, B cells from B-NHLr co-expressed wild-type and multiple,
      normal (CD95nv) and novel alternatively spliced variant CD95 transcripts
      (CD95av). CD95av were predicted, by sequencing, to encode soluble, potentially
      apoptosis inhibitory proteins. However, their overexpression, by transfection, in
      Jurkat cells did not interfere with endogenous CD95 death signalling.
      Furthermore, CD95av-expressing B-NHLr did not show mutations in CD95 splice
      regulatory elements and CD95av expression was 'reversible' by CD40 activation.
      This, in conjunction with treatment by the protein synthesis inhibitor,
      cycloheximide, could sensitise a subset of B-NHLr to CD95 apoptosis. In normal
      and lymphoma B cells, this correlated to increased CD95 membrane expression,
      enhanced DISC activity and engagement of the mitochondrial death pathway via Bid
      cleavage, although the latter occurred less efficiently in B-NHLr. Thus, immune
      modulation of CD95 transcription and alternative splicing combined with enhanced
      engagement of mitochondrial death signalling offer potential for restoration of
      CD95 apoptosis sensitivity in B-NHLr.

PMID- 19751724
TI  - Calpain 1 and Calpastatin expression is developmentally regulated in rat brain.
AB  - Calpains and caspases are cysteine endopeptidases which share many similar
      substrates. Caspases are essential for caspase-dependent apoptotic death where
      calpains may play an augmentive role, while calpains are strongly implicated in
      necrotic cell death morphologies. Previous studies have demonstrated a down
      regulation in the expression of many components of the caspase-dependent cell
      death pathway during CNS development. We therefore sought to determine if there
      is a corresponding upregulation of calpains. The major CNS calpains are the mu
      and m-isoforms, composed of the unique 80 kDa calpain 1 and 2 subunits,
      respectively, and the shared 28 kDa small subunit. In rat brain, relative protein
      and mRNA levels of calpain 1, calpain 2, caspase 3, and the endogenous calpain
      inhibitor-calpastatin, were evaluated using western blot and real-time RT-PCR.
      The developmental time points examined ranged from embryonic day 18 until
      postnatal day 90. Calpain 1 and calpastatin protein and mRNA levels were low at
      early developmental time points and increased dramatically by P30. Conversely,
      caspase-3 expression was greatest at E18, and was rapidly downregulated by P30.
      Calpain 2 protein and mRNA levels were relatively constant throughout the E18-P90
      age range examined. The inverse relationship of calpain 1 and caspase 3 levels
      during CNS development is consistent with the shift from caspase-dependent to
      caspase-independent cell death mechanisms following CNS injury in neonatal vs.
      adult rat brain.

PMID- 19751725
TI  - Subcellular and metabolic examination of amyloid-beta peptides in Alzheimer
      disease pathogenesis: evidence for Abeta(25-35).
AB  - Amyloid-beta peptide (Abeta) is a central player in the pathogenesis and
      diagnosis of Alzheimer disease. It aggregates to form the core of Alzheimer
      disease-associated plaques found in coordination with tau deposits in diseased
      individuals. Despite this clinical relevance, no single hypothesis satisfies and
      explicates the role of Abeta in toxicity and progression of the disease. To
      explore this area, investigators have focused on mechanisms of cellular
      dysfunction, aggregation, and maladaptive responses. Extensive research has been
      conducted using various methodologies to investigate Abeta peptides and
      oligomers, and these multiple facets have provided a wealth of data from specific
      models. Notably, the utility of each experiment must be considered in regards to
      the brain environment. The use of Abeta(25-35) in studies of cellular dysfunction
      has provided data indicating that the peptide is indeed responsible for multiple
      disturbances to cellular integrity. We will review how Abeta peptide induces
      oxidative stress and calcium homeostasis, and how multiple enzymes are
      deleteriously impacted by Abeta(25-35). Understanding and discussing the origin
      and properties of Abeta peptides is essential to evaluating their effects on
      various intracellular metabolic processes. Attention will also be specifically
      directed to metabolic compartmentation in affected brain cells, including
      mitochondrial, cytosolic, nuclear, and lysosomal enzymes.

PMID- 19751726
TI  - Multiple primer PCR for the identification of anisakid nematodes from Taiwan
      Strait.
AB  - There were six major larval anisakid species found in commercial marine fishes
      caught in the Minnan fishing ground in the Taiwan Strait: Anisakis physeteris,
      Anisakis pegreffii, Raphidascaris trichiuri, Contracaecum aduncum, Contracaecum
      muraenesoxi, Contracaecum sp. For rapid identification of the parasite species
      above, a single and a multiple primer PCR (multiplex PCR) method, using specific
      primers based on aligned sequences of the internal transcribed spacer ITS-1,
      5.8S, and ITS-2 of nuclear ribosomal DNA, were jointly used for the rapid
      identification of these anisakid larvae. The primers yielded distinct PCR
      products for each of the anisakid nematodes, providing rapid and accurate tools
      for identifying anisakid nematodes with distinct geographical distribution.

PMID- 19751727
TI  - Diacylglycerol kinase alpha enhances protein kinase Czeta-dependent
      phosphorylation at Ser311 of p65/RelA subunit of nuclear factor-kappaB.
AB  - We recently reported that diacylglycerol kinase (DGK) alpha enhanced tumor
      necrosis factor-alpha (TNF-alpha)-induced activation of nuclear factor-kappaB (NF
      kappaB). However, the signaling pathway between DGKalpha and NF-kappaB remains
      unclear. Here, we found that small interfering RNA-mediated knockdown of DGKalpha
      strongly attenuated protein kinase C (PKC) zeta-dependent phosphorylation of a
      large subunit of NF-kappaB, p65/RelA, at Ser311 but not PKCzeta-independent
      phosphorylation at Ser468 or Ser536. Moreover, knockdown and overexpression of
      PKCzeta suppressed and synergistically enhanced DGKalpha-mediated NF-kappaB
      activation, respectively. These results strongly suggest that DGKalpha positively
      regulates TNF-alpha-dependent NF-kappaB activation via the PKCzeta-mediated
      Ser311 phosphorylation of p65/RelA.

PMID- 19751728
TI  - The cytosolic subunit p67phox of the NADPH-oxidase complex does not bind NADPH.
AB  - The NADPH-oxidase of phagocytic cells is a multicomponent enzyme that generates
      superoxide. It comprises a membrane flavocytochrome b558 and four cytosolic
      proteins; p67phox, p47phox, p40phox and Rac. The NADPH-binding site of this
      complex was shown to be located on the flavocytochrome b558. However, a number of
      studies have suggested the presence of another site on the p67phox subunit which
      is the key activating component. Using several approaches like tryptophan
      quenching fluorescence measurement, inhibition by 2',3'-dialdehyde NADPH, and
      free/bound NADPH concentration measurements, we demonstrate that no NADPH binds
      on p67phox, thus definitively solving the controversy on the number and location
      of the NADPH-binding sites on this complex.

PMID- 19751729
TI  - Enhancement of angiogenic and vasculogenic potential of endothelial progenitor
      cells by haptoglobin.
AB  - Endothelial progenitor cells (EPCs) were transfected with the haptoglobin (Hp)
      gene to investigate the effect of Hp on cell function. Hp potentiated the gene
      expression of various pro-angiogenic factors in the EPCs. The Hp-modified EPCs
      also increased in vitro tube formation on Matrigel compared with control cells.
      In hindlimb ischaemia models, Hp-EPCs showed a greater ability for improving
      blood perfusion and recovery from ischaemic injury. These results indicate that
      Hp improves EPC function in neovasculogenesis, which suggests that ex vivo
      modification of EPCs with the Hp gene can be applied to the treatment of vascular
      damage.

PMID- 19751730
TI  - Time-dependent regulation of muscle caveolin activation and insulin signalling in
      response to high-fat diet.
AB  - We studied the effect of high-fat diet on the expression and activation of the
      three caveolins in rat skeletal muscle and their association with the insulin
      signalling cascade. Initial response was characterized by increased signalling
      through Cav-1 and Cav-3 phosphorylation, suggesting that both participate in an
      initial acute response to the calorie surplus. Afterwards, Cav-1 signalling was
      slightly reduced, whereas Cav-3 remained active. Late chronic phase signalling
      through both proteins was impaired inducing a prediabetic state. Summarizing,
      caveolins seem to mediate a time-dependent regulation of insulin cascade in
      response to high-fat diet in muscle.

PMID- 19751731
TI  - C-terminal binding proteins (CtBPs) attenuate KLF4-mediated transcriptional
      activation.
AB  - We aimed to examine the physical interaction between CtBPs and KLF4 and the
      potential importance of this interaction. Co-immunoprecipitation indicated that
      CtBP1 indeed interacted with KLF4. This was supported by the co-localization of
      both KLF4 and CtBP1 in the promoter regions of KLF4 downstream target genes. In
      addition, overexpression of CtBP1 significantly decreased KLF4-mediated
      transcriptional activation in both an artificial (pGL5) and genuine (IAP and
      Keratin-4) reporter system. Mutations in the potential CtBP binding motif in KLF4
      were accompanied by loss of the inhibitory effect of CtBP1 in the reporter assay
      and of the physical interaction with CtBP1. Overall, our results suggest that
      CtBPs attenuate KLF4-mediated transcriptional activation through the physical
      interaction with KLF4.

PMID- 19751732
TI  - Human cytosolic tRNase ZL can downregulate gene expression through miRNA.
AB  - A long form of tRNase Z (tRNase ZL) can cleave any target RNA at any desired site
      under the direction of artificial small guide RNA including approximately 25
      nucleotide hook-shaped RNA. Here we show that human miR-103 can form a hook
      structure to guide target RNA cleavage by human cytosolic tRNase ZL in vitro. In
      vivo analyses using luciferase mRNAs modified to contain miR-103 target sequences
      in their 3' untranslated regions indicated that miR-103 downregulates gene
      expression through directing mRNA cleavage by tRNase ZL. The present data suggest
      the possibility that human cytosolic tRNase ZL modulates gene expression through
      a subset of microRNAs in the cells.

PMID- 19751733
TI  - Inhibition of lipolysis may contribute to the acute regulation of plasma FFA and
      glucose by FGF21 in ob/ob mice.
AB  - FGF21 is a unique member of the fibroblast growth factors (FGFs) and a novel
      hormone that regulates glucose, lipid, and energy homeostasis. The beneficial
      effects of FGF21 reported thus far have mostly been from chronic treatments. In
      order to better understand the mechanism for FGF21 action, we evaluated the acute
      effects of FGF21 in vivo and in vitro. Here we report that a single injection of
      FGF21 acutely reduced plasma free fatty acid levels similar to its acute effects
      on plasma glucose in ob/ob mice. In vitro, FGF21 inhibited lipolysis in
      adipocytes during a short treatment and reduced total lipase activity. These
      results demonstrate the potential importance of adipocyte lipolysis to the
      observed acute improvements in plasma parameters.

PMID- 19751734
TI  - Endogenous IGF-I and alphaVbeta3 integrin ligands regulate increased smooth
      muscle hyperplasia in stricturing Crohn's disease.
AB  - BACKGROUND & AIMS: Insulin-like growth factor-I (IGF-I) regulates human
      intestinal smooth muscle growth by stimulating proliferation and inhibiting
      apoptosis. IGF-I-stimulated growth is augmented when alphaVbeta3 integrin is
      occupied by its ligands, fibronectin and vitronectin. Increased IGF-I expression
      and muscle cell hyperplasia are features of stricturing Crohn's disease (CD);
      however, the role of IGF-I in stricture formation is unknown. The aim was to
      identify the functional role of endogenous IGF-I and alphaVbeta3 integrin ligands
      in regulating muscle cell hyperplasia in stricturing CD. METHODS: Smooth muscle
      cells were isolated from muscularis propria of stricturing CD or normal margins.
      Quantitative polymerase chain reaction, immunoblot analysis, and enzyme-linked
      immunosorbent assay were used to measure fibronectin, vitronectin, alphaVbeta3
      integrin, and IGF-I levels. Activation of the IGF-I receptor, Erk1/2, p70S6
      kinase, and GSK-3beta was measured by immunoblot. Proliferation was quantified by
      Ki67 immunostaining and [(3)H]thymidine incorporation. Apoptosis was measured
      from caspase-3 cleavage and nucleosome accumulation. RESULTS: IGF-I, vitronectin,
      and fibronectin RNA and protein levels were increased 1.8- to 3.4-fold in muscle
      cells from strictures over normal margins. Basal IGF-I receptor phosphorylation
      was increased 320% in strictured over normal muscle, and basal Erk1/2, p70S6
      kinase, and GSK-3beta phosphorylation were increased 205%-292% in strictures. In
      muscle cells from strictures, Ki67 immunoreactivity and [(3)H]thymidine
      incorporation were increased and apoptosis was decreased compared with normal
      margins. Antagonists of the IGF-I receptor or alphaVbeta3 integrin reversed these
      changes. CONCLUSIONS: Smooth muscle cell hyperplasia in stricturing CD is
      regulated by increased endogenous IGF-I and alphaVbeta3 integrin ligands that
      regulate augmented proliferation and diminished apoptosis.

PMID- 19751735
TI  - Role of placental growth factor in mesenteric neoangiogenesis in a mouse model of
      portal hypertension.
AB  - BACKGROUND & AIMS: Portal hypertension is responsible for the major complications
      associated with cirrhosis. Angiogenesis has been associated with the
      pathophysiology of portal hypertension. We investigated the role of placental
      growth factor (PlGF) and tested the effects of monoclonal antibodies against PlGF
      (alphaPlGF) in a mouse model of portal hypertension. METHODS: Using a mouse model
      of prehepatic portal hypertension, we measured PlGF levels in the mesenteric
      tissue at different time points. We used knockout mice and alphaPlGF to determine
      the role of PlGF in the splanchnic hyperdynamic system and portosystemic
      collateral formation, examining its effects before and after portal hypertension
      was induced. RESULTS: PlGF was significantly up-regulated in the mesenteric
      tissue of mice with portal hypertension. Compared with wild-type animals, the
      vascular density in the mesentery was reduced in PlGF knockout hypertensive mice,
      preventing collateral formation and attenuation of mesenteric artery flow without
      affecting portal pressure. In the prevention study, alphaPlGF showed similar
      findings as in the knockout study. In mice with portal hypertension,
      administration of alphaPlGF resulted in a 32% decrease in portal pressure,
      compared with mice given immunoglobulin G(1) (control). CONCLUSIONS: Pathologic
      angiogenesis in the mesenteric tissues of mice with portal hypertension is
      mediated by PlGF. Blocking PlGF could be an effective strategy for reducing
      collateral formation and lowering portal pressure; further research into the
      effects in cirrhosis is warranted.

PMID- 19751736
TI  - Endocrine mediated phenotypic plasticity: condition-dependent effects of juvenile
      hormone on dominance and fertility of wasp queens.
AB  - There has been increasing interest in the mechanisms that mediate behavioral and
      physiological plasticity across individuals with similar genotypes. Some of the
      most dramatic plasticity is found within and between social insect castes. For
      example, Polistes wasp queens can nest alone, dominate a group of cooperative
      queens, or act as worker-like subordinates who rarely reproduce. Previous work
      suggests that condition-dependent endocrine responses may play a role in
      plasticity between castes in the hymenoptera. Here, we test whether condition
      dependent endocrine responses influence plasticity within castes in the wasp
      Polistes dominulus. We experimentally manipulate juvenile hormone (JH) titers in
      nest-founding queens and assess whether JH mediates variation in behavior and
      physiology. JH generally increased dominance and fertility of queens, but JH's
      effects were not uniform across individuals. JH had a stronger effect on the
      dominance and fertility of large individuals and individuals with facial patterns
      advertising high quality than on the dominance and fertility of small individuals
      and those advertising low quality. These results demonstrate that JH has
      condition-dependent effects. As such, they clarify how JH can mediate different
      behaviors in well nourished queens and poorly nourished workers. Many Polistes
      queens nest cooperatively with other queens, so condition-dependent hormonal
      responses provide a mechanism for queens to adaptively allocate energy based on
      their probability of successfully becoming the dominant queen. Research on the
      endocrine basis of plasticity often focuses on variation in endocrine titers
      alone. However, differential endocrine responses are likely to be a widespread
      mechanism mediating behavioral and physiological plasticity.

PMID- 19751737
TI  - Rapid steroid influences on visually guided sexual behavior in male goldfish.
AB  - The ability of steroid hormones to rapidly influence cell physiology through
      nongenomic mechanisms raises the possibility that these molecules may play a role
      in the dynamic regulation of social behavior, particularly in species in which
      social stimuli can rapidly influence circulating steroid levels. We therefore
      tested if testosterone (T), which increases in male goldfish in response to
      sexual stimuli, can rapidly influence approach responses towards females.
      Injections of T stimulated approach responses towards the visual cues of females
      30-45 min after the injection but did not stimulate approach responses towards
      stimulus males or affect general activity, indicating that the effect is stimulus
      specific and not a secondary consequence of increased arousal. Estradiol produced
      the same effect 30-45 min and even 10-25 min after administration, and treatment
      with the aromatase inhibitor fadrozole blocked exogenous T's behavioral effect,
      indicating that T's rapid stimulation of visual approach responses depends on
      aromatization. We suggest that T surges induced by sexual stimuli, including
      preovulatory pheromones, rapidly prime males to mate by increasing sensitivity
      within visual pathways that guide approach responses towards females and/or by
      increasing the motivation to approach potential mates through actions within
      traditional limbic circuits.

PMID- 19751738
TI  - Corticosterone manipulations alter morph-specific nestling provisioning behavior
      in male white-throated sparrows, Zonotrichia albicollis.
AB  - In the polymorphic white-throated sparrow (Zonotrichia albicollis), tan-striped
      males provision nestlings at higher rates than do white-striped males. In a
      previous study, we found that tan-striped males had lower baseline corticosterone
      levels than white-striped males during the nestling stage. To determine if this
      variation in corticosterone influences morph-specific differences in nestling
      provisioning behavior, we used intraperitoneal osmotic pumps to increase baseline
      corticosterone levels in tan-striped males (TS CORT) and administer RU486, a
      glucocorticoid receptor antagonist, in white-striped males (WS RU486). These
      manipulations essentially reversed morph-specific nestling provisioning behavior
      in males. TS CORT males fed nestlings at lower rates than TS controls (vehicle
      only implant), and at similar rates to WS controls (vehicle-only implant), while
      WS RU486 males fed nestlings at higher rates than WS controls, and at similar
      rates to TS controls. These results demonstrate that (1) increases in baseline
      corticosterone (i.e., below concentrations associated with the adrenocortical
      response to stress) can directly or indirectly inhibit nestling provisioning
      behavior, and (2) corticosterone influences morph-specific variation in parental
      behavior in male white-throated sparrows. This study contributes to the growing
      evidence that modulating baseline CORT mediates parental care and self
      maintenance activities in birds, and thus may serve as a mechanism for balancing
      current reproductive success with survival.

PMID- 19751739
TI  - Preservation of mitochondrial function with cardiopulmonary resuscitation in
      prolonged cardiac arrest in rats.
AB  - During cardiac arrest (CA), myocardial perfusion is solely dependent on
      cardiopulmonary resuscitation (CPR) although closed-chest compressions only
      provide about 10-20% of normal myocardial perfusion. The study was conducted in a
      whole animal CPR model to determine whether CPR-generated oxygen delivery
      preserves or worsens mitochondrial function. Male Sprague-Dawley rats (400-450 g)
      were randomly divided into four groups: (1) BL (instrumentation only, no cardiac
      arrest), (2) CA(15) (15 min cardiac arrest without CPR), (3) CA(25) (25 min
      cardiac arrest without CPR) and (4) CPR (15 min cardiac arrest, followed by 10
      min CPR). The differences between groups were evaluated by measuring
      mitochondrial respiration, electron transport chain (ETC) complex activities and
      mitochondrial ultrastructure by transmission electron microscopy (TEM). The
      CA(25) group had the greatest impairment of mitochondrial respiration and ETC
      complex activities (I-III). In contrast, the CPR group was not different from the
      CA(15) group regarding all measures of mitochondrial function. Complex I was more
      susceptible to ischemic injury than the other complexes and was the major
      determinant of mitochondrial dysfunction. Observations of mitochondrial
      ultrastructure by TEM were compatible with the biochemical results. The findings
      suggest that, despite low blood flow and oxygen delivery, CPR is able to preserve
      heart mitochondrial function and viability during ongoing global ischemia.
      Preservation of complex I activity and mitochondrial function during cardiac
      arrest may be an important mechanism underlying the beneficial effects of CPR
      which have been shown in clinical studies.

PMID- 19751740
TI  - Extracellular matrix remodeling in atrial fibrosis: mechanisms and implications
      in atrial fibrillation.
AB  - Atrial fibrosis has been strongly associated with the presence of heart
      diseases/arrhythmias, including congestive heart failure (CHF) and atrial
      fibrillation (AF). Inducibility of AF as a result of atrial fibrosis has been the
      subject of intense recent investigation since it is the most commonly encountered
      arrhythmia in adults and can substantially increase the risk of premature death.
      Rhythm and rate control drugs as well as surgical interventions are used as
      therapies for AF; however, increased attention has been diverted to
      mineralocorticoid receptor (MR) antagonists including spironolactone as potential
      therapies for human AF because of their positive effects on reducing atrial
      fibrosis and associated AF in animal models. Spironolactone has been shown to
      exert positive effects in human patients with heart failure; however, the
      mechanisms and effects in human atrial fibrosis and AF remain undetermined. This
      review will discuss and highlight developments on (i) the relationship between
      atrial fibrosis and AF, (ii) spironolactone, as a drug targeted to atrial
      fibrosis and AF, as well as (iii) the distinct and common mechanisms important
      for regulating atrial and ventricular fibrosis, inclusive of the key
      extracellular matrix regulatory proteins involved.

PMID- 19751741
TI  - Matricryptic sites control tissue injury responses in the cardiovascular system:
      relationships to pattern recognition receptor regulated events.
AB  - This review addresses new concepts related to the importance of how cells within
      the cardiovascular system respond to matricryptic sites generated from the
      extracellular matrix (ECM) following tissue injury. A model is presented whereby
      matricryptic sites exposed from the ECM result in activation of multiple cell
      surface receptors including integrins, scavenger receptors, and toll-like
      receptors which together are hypothesized to coactivate downstream signaling
      pathways which alter cell behaviors following tissue injury. Of great interest
      are the relationships between matricryptic fragments of ECM called matricryptins
      and other stimuli that activate cells during injury states such as released
      components from cells (DNA, RNA, cytoskeletal components such as actin) or
      products from infectious agents in innate immunity responses. These types of cell
      activating molecules, which are composed of repeating molecular elements, are
      known to interact with pattern recognition receptors that (i) are expressed from
      cell surfaces, (ii) are released from cells following tissue injury, or (iii)
      circulate as components of plasma. Thus, cell recognition of matricryptic sites
      from the ECM appears to be an important component of a broad cell and tissue
      sensory system to detect and respond to environmental cues generated following
      varied types of tissue injury.

PMID- 19751742
TI  - Zipping and unzipping of adenylate kinase: atomistic insights into the ensemble
      of open<-->closed transitions.
AB  - Adenylate kinase (AdK), a phosphotransferase enzyme, plays an important role in
      cellular energy homeostasis. It undergoes a large conformational change between
      an open and a closed state, even in the absence of substrate. We investigate the
      apo-AdK transition at the atomic level both with free-energy calculations and
      with our new dynamic importance sampling (DIMS) molecular dynamics method. DIMS
      is shown to sample biologically relevant conformations as verified by comparing
      an ensemble of hundreds of DIMS transitions to AdK crystal structure
      intermediates. The simulations reveal in atomic detail how hinge regions
      partially and intermittently unfold during the transition. Conserved salt bridges
      are seen to have important structural and dynamic roles; in particular, four
      ionic bonds that open in a sequential, zipper-like fashion and, thus, dominate
      the free-energy landscape of the transition are identified. Transitions between
      the closed and open conformations only have to overcome moderate free-energy
      barriers. Unexpectedly, the closed state and the open state encompass broad free
      energy basins that contain conformations differing in domain hinge motions by up
      to 40 degrees . The significance of these extended states is discussed in
      relation to recent experimental Forster resonance energy transfer measurements.
      Taken together, these results demonstrate how a small number of cooperative key
      interactions can shape the overall dynamics of an enzyme and suggest an "all-or
      nothing" mechanism for the opening and closing of AdK. Our efficient DIMS
      molecular dynamics computer simulation approach can provide a detailed picture of
      a functionally important macromolecular transition and thus help to interpret and
      suggest experiments to probe the conformational landscape of dynamic proteins
      such as AdK.

PMID- 19751743
TI  - Non-sequence-specific interactions can account for the compaction of proteins
      unfolded under "native" conditions.
AB  - Proteins unfolded by high concentrations of chemical denaturants adopt expanded,
      largely structure-free ensembles of conformations that are well approximated as
      random coils. In contrast, globular proteins unfolded under less denaturing
      conditions (via mutations, or transiently unfolded after a rapid jump to native
      conditions) and molten globules (arising due to mutations or cosolvents) are
      often compact. Here we explore the origins of this compaction using a truncated
      equilibrium-unfolded variant of the 57-residue FynSH3 domain. As monitored by far
      UV circular dichroism, NMR spectroscopy, and hydrogen-exchange kinetics, CDelta4
      (a 4-residue carboxy-terminal deletion variant of FynSH3) appears to be largely
      unfolded even in the absence of denaturant. Nevertheless, CDelta4 is quite
      compact under these conditions, with a hydrodynamic radius only slightly larger
      than that of the native protein. In order to understand the origins of this
      molten-globule-like compaction, we have characterized a random sequence
      polypeptide of identical amino acid composition to CDelta4. Notably, we find that
      the hydrodynamic radius of this random sequence polypeptide also approaches that
      of the native protein. Thus, while native-like interactions may contribute to the
      formation of compact "unfolded" states, it appears that non-sequence-specific
      monomer-monomer interactions can also account for the dramatic compaction
      observed for molten globules and the "physiological" unfolded state.

PMID- 19751744
TI  - eIF1 controls multiple steps in start codon recognition during eukaryotic
      translation initiation.
AB  - Eukaryotic translation initiation factor (eIF) 1 is a central mediator of start
      codon recognition. Dissociation of eIF1 from the preinitiation complex (PIC)
      allows release of phosphate from the G-protein factor eIF2, triggering downstream
      events in initiation. Mutations that weaken binding of eIF1 to the PIC decrease
      the fidelity of start codon recognition (Sui(-) phenotype) by allowing increased
      eIF1 release at non-AUG codons. Consistent with this, overexpression of these
      mutant proteins suppresses their Sui(-) phenotypes. Here, we have examined
      mutations at the penultimate residue of eIF1, G107, that produce Sui(-)
      phenotypes without increasing the rate of eIF1 release. We provide evidence that,
      in addition to its role in gating phosphate release, dissociation of eIF1
      triggers conversion from an open, scanning-competent state of the PIC to a
      stable, closed one. We also show that eIF5 antagonizes binding of eIF1 to the
      complex and that key interactions of eIF1 with its partners are modulated by the
      charge at and around G107. Our data indicate that eIF1 plays multiple roles in
      start codon recognition and suggest that prior to AUG recognition it prevents
      eIF5 from binding to a key site in the PIC required for triggering downstream
      events.

PMID- 19751745
TI  - Chronic aortic denervation decreases anxiety and impairs social memory in rats.
AB  - AIMS: The present study investigates anxiety-like behaviour and social cognitive
      performance in rats with chronic aortic denervation. MAIN METHODS: The aortic
      depressor nerve was bilaterally transected in Wistar rats, causing an almost
      complete disruption of baroreceptors. Bilateral aortic denervated (bAD), sham
      operated (SHAM), and intact (CTRL) rats performed an elevated plus-maze test and
      an olfactory social memory test, one and three months after operation. Blood
      pressure and heart rate were monitored in all animals. KEY FINDINGS: Systolic
      blood pressure, blood pressure lability and heart rate were elevated in bAD rats
      compared to SHAM and CTRL rats. In the elevated plus-maze test, bAD rats spent
      clearly more time in investigating open arms and performed more open arm entries
      than SHAM and CTRL rats during both testing sessions. The olfactory social memory
      test revealed that acquisition time during first contact with a juvenile rat did
      not differ between the groups of rats. The recognition time spent by SHAM and
      CTRL group of rats was distinctly decreased in comparison to the acquisition
      time, an indication of social memory. bAD rats investigated the juvenile rat
      during the second contact to a similar extent than during the first contact, both
      one and three months after denervation. SIGNIFICANCE: These results suggest that
      bilateral aortic denervation induces chronic neurogenic hypertension and elevated
      blood pressure lability, decreases anxiety-like behaviour and deteriorates social
      memory in rats while acquiring of social information is not affected.

PMID- 19751746
TI  - Environmental factors in the development of chronic inflammation: a case-control
      study on risk factors for Crohn's disease within New Zealand.
AB  - The role of environmental factors in the risk for Crohn's disease (CD), an
      inflammatory bowel disease (IBD), was investigated in a North Island-based New
      Zealand case-control cohort. A total of 315 CD patients and 536 controls were
      recruited through various sources to the Auckland CD Risk Factor Study. As well
      as demographic characteristics, the self-reported questionnaire included (1)
      smoking and drinking alcohol, (2) breastfeeding in infancy, (3) early life
      exposures to allergens and microbes, (4) health conditions lasting 6 months or
      longer and (5) taking antibiotics and any medications. There was strong evidence
      for familial associations of the disease, and minor effects of birth order and
      number of siblings. Being a smoker, especially over a long time period, and
      exposure to smoking during childhood and adolescence periods increased risk,
      whereas drinking alcohol at least once per week showed a slight protective
      effect. Long term use of the oral contraceptive pill increased the risk of
      developing CD, but breastfeeding and immunisation during infancy showed no
      significant association. Long term and debilitating illness (lasting 6 months or
      more), taking antibiotics prior to developing CD, or taking four or more
      antibiotics or any regular medication in a year during adolescence substantially
      increased the CD risk. Having a pet during childhood was a protective factor, but
      regularly feeding an animal was not sufficient to protect. Many of these
      significant factors are likely to impact on the colonic microflora and/or immune
      system. We conclude that, in addition to strong evidence for genetic
      associations, factors likely to impact on immune response or reduce early
      exposure to microbes provide a main risk factor for CD in this New Zealand
      population.

PMID- 19751747
TI  - Coupling of the nucleotide incision and 3'-->5' exonuclease activities in
      Escherichia coli endonuclease IV: Structural and genetic evidences.
AB  - Aerobic respiration generates reactive oxygen species (ROS) as a by-product of
      cellular metabolism which can damage DNA. The complex nature of oxidative DNA
      damage requires actions of several repair pathways. Oxidized DNA bases are
      substrates for two overlapping pathways: base excision repair (BER) and
      nucleotide incision repair (NIR). In the BER pathway a DNA glycosylase cleaves
      the N-glycosylic bond between the abnormal base and deoxyribose, leaving either
      an abasic site or single-stranded DNA break. Alternatively, in the NIR pathway,
      an apurinic/apyrimidinic (AP) endonuclease incises duplex DNA 5' next to
      oxidatively damaged nucleotide. The multifunctional Escherichia coli endonuclease
      IV (Nfo) is involved in both BER and NIR pathways. Nfo incises duplex DNA 5' of a
      damaged residue but also possesses an intrinsic 3'-->5' exonuclease activity.
      Herein, we demonstrate that Nfo-catalyzed NIR and exonuclease activities can
      generate a single-strand gap at the 5' side of 5,6-dihydrouracil residue.
      Furthermore, we show that Nfo mutants carrying amino acid substitutions H69A and
      G149D are deficient in both NIR and exonuclease activities, suggesting that these
      two functions are genetically linked and governed by the same amino acid
      residues. The crystal structure of Nfo-H69A mutant reveals the loss of one of the
      active site zinc atoms (Zn1) and rearrangements of the catalytic site, but no
      gross changes in the overall enzyme conformation. We hypothesize that these minor
      changes strongly affect the DNA binding of Nfo. Decreased affinity may lead to a
      different kinking angle of the DNA helix and this in turn thwart nucleotide
      incision and exonuclease activities of Nfo mutants but to lesser extent of their
      AP endonuclease function. Based on the biochemical and genetic data we propose a
      model where nucleotide incision coupled to 3'-->5' exonuclease activity prevents
      formation of lethal double-strand breaks when repairing bi-stranded clustered DNA
      damage.

PMID- 19751748
TI  - Real-time studies of conformational dynamics of the repair enzyme E. coli
      formamidopyrimidine-DNA glycosylase and its DNA complexes during catalytic cycle.
AB  - Fpg protein from Escherichia coli belongs to the class of DNA glycosylases/abasic
      site lyases excising several oxidatively damaged purines in the base excision
      repair pathway. In this review, we summarize the results of our studies of Fpg
      protein from E. coli, elucidating the intrinsic mechanism of recognition and
      excision of damaged bases in DNA.

PMID- 19751749
TI  - Risk of malignant pleural mesothelioma and polymorphisms in genes involved in the
      genome stability and xenobiotics metabolism.
AB  - Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer mostly
      attributable to asbestos exposure. Many polymorphic genes encoding for xenobiotic
      and oxidative metabolism enzymes (XME) or involved in genome stability (GS) can
      modulate individual MPM risk in exposed populations. An association study was
      carried out in a case-control setting including 119 MPM patients and two groups
      of referent subjects (104 with and 695 without documented asbestos exposure).
      Forty-eight polymorphisms in XME genes and 75 in GS-genes were evaluated.
      Statistical analysis revealed some significant associations of studied
      polymorphisms with MPM risk, but most of them disappeared after applying
      Bonferroni correction (new threshold for statistical significance: p=4.07 x 10(
      4)). On the other hand, the nucleotidic change 282C>T within NAT2 held the
      statistical significance (OR=3.54; 95% CI 1.75-7.16; p=0.0002), reinforcing
      existing evidences that describe genetic polymorphisms of NAT2 possibly involved
      in the etiology of the MPM.

PMID- 19751750
TI  - Effects of symbol type and numerical distance on the human event-related
      potential.
AB  - This study investigated the influence of the symbol type and numerical distance
      of numbers on the amplitudes and peak latencies of event-related potentials
      (ERPs). Our aim was to (1) determine the point in time of magnitude information
      access in visual number processing; and (2) identify at what stage the advantage
      of Arabic digits over Chinese verbal numbers occur. ERPs were recorded from 64
      scalp sites while subjects (n=26) performed a classification task. Results showed
      that larger ERP amplitudes were elicited by numbers with distance-close condition
      in comparison to distance-far condition in the VPP component over centro-frontal
      sites. Furthermore, the VPP latency varied as a function of the symbol type, but
      the N170 did not. Such results demonstrate that magnitude information access
      takes place as early as 150 ms after onset of visual number stimuli and the
      advantage of Arabic digits over verbal numbers should be localized to the VPP
      component. We establish the VPP component as a critical ERP component to report
      in studies of numerical cognition and our results call into question the N170/VPP
      association hypothesis and the serial-stage model of visual number comparison
      processing.

PMID- 19751751
TI  - Diet-induced obesity alters behavior as well as serum levels of corticosterone in
      F344 rats.
AB  - Obesity is an increasing socio-economic health problem. Diet-induced obese (DIO)
      rodents are widely used as a model of obesity in humans. However, there is no
      comprehensive data about the behavioral phenotype of DIO rodents. Therefore, the
      aim of the present study was to determine whether a high-fat-diet changes
      behavioral patterns of DIO Fischer 344 (F344) rats in comparison with lean
      littermates. The behavioral tests (homecage, holeboard, social interaction, and
      hotplate) were performed in 28 normal-weight and 28 male DIO F344 rats (mean age:
      16 weeks) and revealed a significantly higher level of anxiety- and aggression
      related parameters in obese rats, whereas their pain threshold was significantly
      lower. Fitting to a different behavioral response, basal corticosterone levels
      (measured by RIA) of obese animals were significantly elevated (16.0ng/ml vs.
      12.5ng/ml; p<0.01). We conclude that obese rats differ in various aspects from
      their lean littermates. The altered behavioral characteristics displayed by DIO
      F344 rats have to be considered in further experiments involving DIO rodents.

PMID- 19751752
TI  - Gastric emptying and intestinal absorption of ingested water and saline by
      hypovolemic rats.
AB  - Recent experiments showed that in a one-bottle test conducted 16h after sc
      injection of polyethylene glycol (PEG) solution, hypovolemic rats consumed water
      or 0.30 M NaCl in an initial drinking episode but did not empty the ingested
      fluid from the stomach or absorb it from the small intestine very rapidly,
      certainly not as rapidly as when 0.15M NaCl was consumed (Smith et al., Am J
      Physiol 292: R2089-R2099, 2007). The present experiments examined the patterns of
      water and 0.30 M NaCl ingestion and the movement of consumed fluid through the
      gastrointestinal tract when PEG-treated rats were given a two-bottle delayed
      access test. We found that both fluids always were consumed in the first drinking
      episode, that the fluid mixture ingested was equivalent to 0.10-0.15M NaCl, and
      that gastric emptying rate and net fluid absorption from the small intestine
      usually were much faster than when PEG-treated rats drank either water or
      hypertonic saline alone. Thus, ingestion of water and 0.30 M NaCl by hypovolemic
      rats in the same episode adaptively facilitated the movement into the circulation
      of a near-isotonic fluid that is ideal for restoring plasma volume deficits.

PMID- 19751753
TI  - A predator-prey refuge system: Evolutionary stability in ecological systems.
AB  - A refuge model is developed for a single predator species and either one or two
      prey species where no predators are present in the prey refuge. An individual's
      fitness depends on its strategy choice or ecotype (predators decide which prey
      species to pursue and prey decide what proportion of their time to spend in the
      refuge) as well as on the population sizes of all three species. It is shown
      that, when there is a single prey species with a refuge or two prey species with
      no refuge compete only indirectly (i.e. there is only apparent competition
      between prey species), that stable resident systems where all individuals in each
      species have the same ecotype cannot be destabilized by the introduction of
      mutant ecotypes that are initially selectively neutral. In game-theoretic terms,
      this means that stable monomorphic resident systems, with ecotypes given by a
      Nash equilibrium, are both ecologically and evolutionarily stable. However, we
      show that this is no longer the case when the two indirectly-competing prey
      species have a refuge. This illustrates theoretically that two ecological
      factors, that are separately stabilizing (apparent competition and refuge use),
      may have a combined destabilizing effect from the evolutionary perspective. These
      results generalize the concept of an evolutionarily stable strategy (ESS) to
      models in evolutionary ecology. Several biological examples of predator-prey
      systems are discussed from this perspective.

PMID- 19751754
TI  - Autophagy upregulation and loss of NF-kappaB in oxidative stress-related
      immunodeficient SAMP8 mice.
AB  - Aged spleens from senescence-accelerated prone mice 8 (SAMP8) and senescence
      accelerated resistant mice 1 (SAMR1) were examined to determine whether sex or
      melatonin had an effect on oxidative stress-related immune impairments. We
      observed that the immunosenescence of SAMP8 mice was associated with a redox
      imbalance, leading to an age-related increase in oxidative damage, resulting from
      a decrease in antioxidant defense and protease activity. Moreover, increased
      apoptotic cell death, a decrease in proliferative activity and the loss of NF
      kappaB activation were also related to the immunodeficiency seen in SAMP8
      compared to SAMR1 mice. Females demonstrated higher oxidative stress-related
      alterations in the immune response, and subsequent, melatonin treatment provided
      the best protective effects. Pathways involved in autophagy were upregulated in
      SAMP8 as an adaptive response to oxidative stress, in an attempt to rescue the
      cell from increased apoptosis and age-related immunodeficiency. However, the NF
      kappaB signaling and autophagic processes were unaffected by treatment with
      melatonin. Therefore, we propose a key role for NF-kappaB signaling and autophagy
      in the oxidative stress-related immunosenescent spleens of SAMP8 mice.

PMID- 19751755
TI  - Acute sleep deprivation increases the rate and efficiency of cocaine self
      administration, but not the perceived value of cocaine reward in rats.
AB  - Relapse to drug seeking and drug taking is elicited by exposure to stress, drug
      associated cues, or drugs of abuse themselves. According to the clinical
      literature, relapse also can be elicited in humans by sleep deprivation. Even so,
      the effect of sleep deprivation on drug-seeking and drug-taking behaviors has
      received relatively little attention in the laboratory (i.e., currently, no
      animal model exists) and the underlying circuitry remains unexplored. In the
      present study, 42 naive male Sprague-Dawley rats were trained to self-administer
      cocaine and were then divided, on the basis of their behavior, into low (n=20)
      and high (n=22) drug-taking groups. Self-administration behavior was
      extinguished, and the effect of acute sleep deprivation (0, 4, or 8h) on drug
      induced reinstatement and on progressive ratio responding (i.e., on the
      motivation to work for drug) was investigated. The results showed that, relative
      to low drug-takers, high drug-takers took more drug in acquisition, made more
      infusion attempts during drug-induced reinstatement, worked harder for drug, and
      exhibited greater goal-directed behavior. Acute sleep deprivation had little
      impact on high drug-takers beyond increasing the rate of infusions self
      administered during progressive ratio (PR) testing. Conversely, in low drug
      takers, acute sleep deprivation completely abolished cocaine-induced
      reinstatement during extinction testing. During PR testing, however, sleep
      deprivation increased the speed with which low drug-taking rats initiated
      responding for drug, increased the rate of infusions, and increased goal-directed
      behavior. It did not, however, increase the perceived value of the cocaine reward
      (i.e., neither sleep-deprived low drug-takers nor high drug-takers exhibited a
      higher break point for cocaine than their non-deprived counterparts). These data
      are the first to demonstrate a direct link between sleep deprivation and
      responding for cocaine, particularly in subjects that would otherwise respond
      little for drug.

PMID- 19751756
TI  - Learning deficits in C57BL/6J mice following perinatal arsenic exposure:
      consequence of lower corticosterone receptor levels?
AB  - Most studies on arsenic as a drinking water contaminant have focused on its
      carcinogenic potential but a few suggest that arsenic can adversely affect
      cognitive development. One parameter of the hypothalamic-pituitary-adrenal axis,
      the corticosterone receptor (CR) has been shown to be altered by arsenic. These
      receptors are found throughout the central nervous system, particularly in the
      hippocampus, an area of the brain of central importance for learning and memory.
      We examined the impact of perinatal exposure to 50 parts per billion (ppb) sodium
      arsenate on CRs and learning and memory behavior in the C57BL/6J mouse.
      Measurements of CRs revealed that arsenic-exposed offspring have significantly
      lower levels of these receptors in the nucleus than controls. Exposed offspring
      showed longer latency to approach a novel object than controls in an object
      recognition task. In the 8-way radial arm maze, arsenic offspring had a
      significant increase in the number of entry errors compared to controls. Results
      suggest that moderate exposures to perinatal arsenic can significantly reduce CR
      levels in the hippocampus and can have adverse effects on learning and memory
      behavior.

PMID- 19751757
TI  - Neighborhood SES and walkability are related to physical activity behavior in
      Belgian adults.
AB  - OBJECTIVE: To investigate whether neighborhood walkability (higher residential
      density, land use mix, street connectivity) is positively associated with
      physical activity in Belgian adults and whether this association is moderated by
      neighborhood SES. METHODS: The Belgian Environmental Physical Activity Study
      (BEPAS) was conducted in Ghent, Belgium. Data were collected between May 2007 and
      September 2008. Twenty-four neighborhoods were selected, stratified on GIS-based
      walkability and neighborhood SES. In total, 1200 adults (aged 20-65 years; 50 per
      neighborhood) completed the International Physical Activity Questionnaire and
      wore an accelerometer for seven days. After omitting participants with missing
      accelerometer data, the final sample consisted of 1166 adults. RESULTS: Living in
      a high-walkable neighborhood was associated with more accelerometer-based minutes
      of moderate-to-vigorous physical activity (38.6 vs. 31.8 min/day, p<0.001),
      transportational walking and cycling, recreational walking, and less motorized
      transport (all p<0.05). Low neighborhood SES was related to more cycling for
      transport and less motorized transport (all p<0.05). No interactions between
      walkability and neighborhood SES were found. CONCLUSIONS: The BEPAS results
      generally confirmed the findings from Australia and the US showing that, in
      Europe, walkability is also positively related to physical activity. As
      neighborhood SES was not a significant moderator, walkability appears beneficial
      for all economic strata.

PMID- 19751758
TI  - A comparison study on microwave-assisted extraction of Artemisia sphaerocephala
      polysaccharides with conventional method: Molecule structure and antioxidant
      activities evaluation.
AB  - The conventional extraction methods for polysaccharides were time-consuming,
      laborious and energy-consuming. Microwave-assisted extraction (MAE) technique was
      employed for the extraction of Artemisia sphaerocephala polysaccharides (ASP),
      which is a traditional Chinese food. The extracting parameters were optimized by
      Box-Behnken design. In microwave heating process, a decrease in molecular weight
      (M(w)) was detected in SEC-LLS measurement. A d(f) value of 2.85 indicated ASP
      using MAE exhibited as a sphere conformation of branched clusters in aqueous
      solution. Furthermore, it showed stronger antioxidant activities compared with
      hot water extraction. The data obtained showed that the molecular weights played
      a more important role in antioxidant activities.

PMID- 19751759
TI  - In vitro antiherpetic and antirotaviral activities of a sulfate prepared from
      Mimosa scabrella galactomannan.
AB  - A chemically sulfated galactomannan (BRS) from seeds of Mimosa scabrella had in
      vitro antiviral activity against Herpes simplex virus 1 (HSV-1), but not against
      Simian rotavirus A/SA11 (SiRV-A/SA11). It was examined by (13)C NMR spectroscopy,
      which showed the sulfate groups to be mainly at C-6 of galactose residues. BRS
      had a selective inhibition against HSV-1 during its attachment step, having an
      IC(50) lower than 2.5microg/ml, determined by plaque reduction, and a selectivity
      index of greater than 181, suggesting that the antiviral effect is likely due to
      interactions between the virus and BRS, being influenced its overall surface
      charge.

PMID- 19751760
TI  - A clip domain serine proteinase plays a role in antibacterial defense but is not
      required for prophenoloxidase activation in shrimp.
AB  - The clip domain serine proteinases (clip-SPs) play critical roles in the
      signaling processes during embryonic development and in the innate immunity of
      invertebrates. In the present study, we identified a homolog of the clip-SP,
      designated as PmClipSP1, by searching the Penaeus monodon EST database
      (http://pmonodon.biotec.or.th), and using RACE-PCR to obtain the complete gene
      which contained a 1101bp open reading frame encoding 366 amino acids with a 25
      amino acid signal peptide. The deduced PmClipSP1 protein sequence, which shares a
      predicted structural similarity to the clip-SPs of other arthropod species,
      appears to possess a clip domain at the N-terminus and an enzymatically active
      serine proteinase domain at the C-terminus. Tissue distribution analyses revealed
      that, at the transcript level, PmClipSP1 is mainly expressed in shrimp hemocytes,
      whilst temporal gene expression analyses showed that the hemocyte PmClipSP1
      transcript levels were upregulated at 3h and downregulated at 6-48h following
      systemic Vibrio harveyi infection. RNAi-mediated silencing of the PmClipSP1 gene,
      by injection of double-stranded RNA (dsRNA) corresponding to the PmClipSP1 gene
      into shrimp, significantly reduced PmClipSP1 transcript levels, but neither
      significantly altered the other clip-SP and clip-SPH transcript levels nor
      reduced the total phenoloxidase (PO) enzyme activity in shrimp hemocytes,
      compared to the levels seen in the GFP dsRNA control, suggesting that PmClipSP1
      is not involved in the proPO system. However, suppression of the PmClipSP1 gene
      led to a significant increase in the number of viable bacteria in the hemolymph
      (approximately 2.4-fold) and in the mortality rate (59%) of shrimp systemically
      infected with V. harveyi. These findings suggest that PmClipSP1 plays a role in
      the antibacterial defense mechanism of P. monodon shrimp.

PMID- 19751761
TI  - Close relationships, inflammation, and health.
AB  - Different aspects of personal relationships including social integration, social
      support, and social conflict have been related to inflammation. This article
      summarizes evidence linking the quality and quantity of relationships with gene
      expression, intracellular signaling mechanisms, and inflammatory biomarkers, and
      highlights the biological and psychological pathways through which close
      relationships impact inflammatory responses. Relationship conflict and lower
      social support can effectively modulate proinflammatory cytokine secretion both
      directly (via CNS/neural/endocrine/immune biobehavioral pathways), and
      indirectly, by promoting depression, emotional stress responses, and detrimental
      health behaviors. Accordingly, thorough assessments of health behaviors and
      attention to key methodological issues are necessary to identify the
      contributions of relationships to inflammation, and thus we highlight procedural
      issues to be considered in the design of studies. Despite some notable
      methodological challenges, the evidence suggests that learning more about how
      close relationships influence inflammation will provide important new insights
      into the ways that relationships impact health.

PMID- 19751762
TI  - Disruptions of the mother-infant relationship and stress-related behaviours:
      altered corticosterone secretion does not explain everything.
AB  - The hypothalamic-pituitary-adrenal (HPA) axis is the main neuroendocrine system
      of response to stress, and an imbalance of this system's activity is believed to
      be at the core of numerous psychiatric pathologies. During the neonatal period,
      the glucocorticoid response to stress is maintained at low levels by specific
      maternal behaviours, which is essential for proper brain development. Effective
      evaluation of the impact of increased secretion of corticosterone during an
      essentially anabolic developmental period on adulthood behaviour involved
      separation of the neonate from its mother for periods ranging from 3 to 24h. It
      has been shown that disinhibition of the stress response is achieved by such
      procedures. The pioneering studies by Seymour Levine set the stage for a prolific
      and promising field of study that may help neuroscientists unveil the
      neurobiological underpinnings of stress-related disorders. Based on a series of
      studies, we propose that maternal separation and maternal deprivation change
      stress-related behaviours, but that corticosterone seem to be only partially
      involved in these changes in adulthood. It appears that extra-hypothalamic
      corticotrophin-releasing factor and neurotransmitter systems may be the primary
      mediators of these behavioural outcomes.

PMID- 19751763
TI  - Neurobehavioural effects of pesticides with special focus on organophosphorus
      compounds: which is the real size of the problem?
AB  - The risk of neurobehavioural impairment as a consequence of a prolonged, low dose
      exposure to neurotoxic pesticides is not clearly demonstrated despite numerous
      publications addressing the topic. We reviewed the 24 papers published on human
      neurobehavioural effects of organophosphorus and/or carbamates pesticides up to
      May 1st 2008. Variables evaluated were compound/s addressed, number of subjects,
      approach to measure or estimate exposure, characteristics of control groups and
      presence of confounders, methodological approach, and type of alteration, taking
      into account cognitive, sensory-motor, psychological, and psychomotor measures. A
      total of 6 papers considered the whole spectrum of functions, the studies
      yielding positive or uncertain results were 13 (68%) for cognitive function, 11
      (69%) for psychomotor function, 11 (65%) for sensory-motor function, and 11 (65%)
      for psychological function impairment. In 46% of the positive studies a previous
      severe acute poisoning was reported. Exposure levels were measured only in 5
      studies, and very often there were problems in the selection of controls, and
      firm conclusions on the risk of neurobehavioural effects cannot be reached yet.
      The main limits of the available data are: limited number of studies and
      compounds addressed, significant differences in the approach among studies, poor
      concordance of the results of different studies, and difficulties in controlling
      confounding factors. Nevertheless, there are sufficient data to conclude that
      neurobehavioural impairment might be the consequence of an acute poisoning, and
      possibly the consequence of relatively high and prolonged exposures.

PMID- 19751764
TI  - Granulocyte-colony stimulating factor in experimental stroke and its effects on
      infarct size and functional outcome: A systematic review.
AB  - BACKGROUND: Granulocyte-colony stimulating factor (G-CSF) shows promise as a
      treatment for stroke. This systematic review assesses G-CSF in experimental
      ischaemic stroke. METHODS: Relevant studies were identified with searches of
      Medline, Embase and PubMed. Data were extracted on stroke lesion size,
      neurological outcome and quality, and analysed using Cochrane Review Manager
      using random effects models; results are expressed as standardised mean
      difference (SMD) and odds ratio (OR). RESULTS: Data were included from 19
      publications incorporating 666 animals. G-CSF reduced lesion size significantly
      in transient (SMD -1.63, p<0.00001) but not permanent (SMD -1.56, p=0.11) focal
      models of ischaemia. Lesion size was reduced at all doses and with treatment
      commenced within 4 h of transient ischaemia. Neurological deficit (SMD -1.37,
      p=0.0004) and limb placement (SMD -1.88, p=0.003) improved with G-CSF; however,
      locomotor activity (> or =4 weeks post-ischaemia) was not (SMD 0.76, p=0.35).
      Death (OR 0.27, p<0.0001) was reduced with G-CSF. Median study quality was 4
      (range 0-7/8); Egger's test suggested significant publication bias (p<0.001).
      CONCLUSIONS: G-CSF significantly reduced lesion size in transient but not
      permanent models of ischaemic stroke. Motor impairment and death were also
      reduced. Further studies assessing dose response, administration time, length of
      ischaemia and long-term functional recovery are needed.

PMID- 19751765
TI  - TLR-9 signaling and TCR stimulation co-regulate CD8(+) T cell-associated PD-1
      expression.
AB  - Elevated Programmed Death-1 (PD-1) expression can inhibit T cell activity and is
      a potential barrier to achieving persisting and optimal immunity via therapeutic
      vaccination. Using a direct lymph node-targeted vaccination procedure that
      enabled uncoupling of synthetic peptide (signal 1, TCR-mediated) and adjuvant
      (signal 2, non-TCR-mediated), we evaluated the impact of varied doses of Toll
      like receptor (TLR)-9 ligand CpG oligodeoxynucleotide (ODN) adjuvant on epitope
      specific CD8(+) T cell-associated PD-1 expression. Peptide vaccination without
      adjuvant yielded CD8(+) T cells with significantly elevated PD-1 expression. This
      conferred impaired function ex vivo, but was reversible by antibody-mediated PD-1
      blockade. By comparison, peptide vaccination with escalating doses of CpG ODN
      adjuvant yielded higher magnitudes of CD8(+) T cells with progressively lower PD
      1 expression and greater ex vivo function. CpG ODN adjuvant in context of
      titrated peptide doses for vaccination yielded the lowest overall PD-1 expression
      levels, demonstrating that fine-tuning both TCR-independent (adjuvant dose) and 
      dependent (antigen dose) stimuli can synergize to co-regulate PD-1 expression on
      epitope-specific CD8(+) T cells. These data hint at strategies to elicit PD
      1(low) CD8(+) T cells using TLR-9 ligand adjuvants, and also shed light on the PD
      1-regulated homeostasis of CD8(+) T cells.

PMID- 19751766
TI  - A real-time PCR assay for quantification of canine adenoviral vectors.
AB  - The pre-existing humoral and cellular immunity found in the great majority of the
      population raises concerns about the clinical efficacy and safety of vectors
      derived from ubiquitous human adenovirus serotypes. To alleviate these concerns,
      canine adenovirus type 2 vectors (CAV-2) were developed. Owing to their
      extraordinary neuronal tropism and efficient axonal retrograde transport, CAV-2
      vectors hold great promise for the treatment of neurodegenerative diseases. The
      development and validation of a SYBR Green qPCR assay for determination of CAV-2
      titers is reported in the present study. This method uses specific primers
      designed to amplify a small genomic fragment of CAV-2 structural genes (pVI
      hexon). The method was accurate and reproducible as determined by the low intra-
      and inter-assay variability (<15% R.S.E.). It is sensitive and useful over a 5
      log range (1 x 10(3) to 1 x 10(7)genome copies/reaction). The assay can be used
      to quantify purified vector samples as well as crude viral lysates. The titers
      obtained by qPCR correlated well with both, those obtained by OD(260) and
      TCID(50) as indicated by the high coefficients of determination obtained by
      regression analysis (r(2)>0.83). The development of this simple and rapid CAV-2
      quantitation method should be helpful for process development and monitoring.

PMID- 19751767
TI  - Application of proteomics methods for pathogen discovery.
AB  - Proteomics have been used widely to study proteins in complex materials such as
      cells, body fluids, tissues, and organisms. Application of advance proteomic
      techniques for the characterization of disease-specific proteins may provide
      information for the detection of potential infectious agents. In this report, two
      proteomics techniques, a two-dimensional differential gel electrophoresis (2D
      DIGE) and a one-dimensional gel electrophoresis and one-dimensional liquid
      chromatography coupled with mass spectrometry (GeLC-MS/MS), were applied for
      investigating viral proteins from cultured cells inoculated with a clinical
      sample. The 2D-DIGE method identified five viral proteins of vaccinia virus that
      are only present in infected cells, these results are in agreement with findings
      determined by genome based methods. The GeLC-MS/MS method identified eight
      vaccinia virus proteins out of 428 proteins detected in the sample. These results
      demonstrate that proteomic techniques can be used effectively for the detection
      of infectious agents. Given that the methods are capable of applying to proteins
      without a prior knowledge of the pathogen present, proteomics has a potential of
      being developed as a molecular tool for pathogen discovery, and disease diagnosis
      of emerging infectious diseases and for bioterrorism defense.

PMID- 19751768
TI  - Novel means of viral antigen identification: improved detection of avian
      influenza viruses by proximity ligation.
AB  - Recent outbreaks of avian influenza in different parts of the world have caused
      major economic losses for the poultry industry, affected wildlife seriously and
      present a significant threat even to human public health, due to the risk for
      zoonotic transmission. The ability to recognize avian influenza viruses (AIVs)
      early is of paramount importance to ensure that appropriate measures can be taken
      quickly to contain the outbreak. In this study, the performance of a proximity
      ligation assay (PLA) for the detection of AIV antigens in biological specimens
      was evaluated. It is shown that PLA: (i) as a novel principle of highly sensitive
      antigen detection is extending the arsenal of tools for the diagnosis of AIV;
      (ii) is very specific, nearly as sensitive as a commonly used reference real-time
      PCR assay, and four orders of magnitude more sensitive than a sandwich ELISA,
      utilizing the same antibody; (iii) avoids the necessity of nucleic acids
      extraction, which greatly facilitates high-throughput implementations; (iv)
      allows the use of inactivated samples, which safely can be transported from the
      field to diagnostic laboratories for further analysis. In summary, the results
      demonstrate that PLA is suited for rapid, accurate and early detection of AIV.

PMID- 19751769
TI  - Reversal of learning deficits in hAPP transgenic mice carrying a mutation at
      Asp664: a role for early experience.
AB  - In addition to the cleavages that generate amyloid-beta (Abeta), the Abeta
      precursor protein (APP) is processed at Asp664, releasing a second toxic peptide
      (APP-C31). Transgenic mice otherwise identical to a well-characterized model of
      AD, PDAPP mice, but carrying a mutation that obliterates Asp664 show a reversal
      of AD-like deficits in memory and in non-cognitive components of behaviour in
      spite of accumulating high levels of Abeta. These results suggest that cleavage
      of APP at Asp664 plays a role in the generation of AD-like deficits, and that a
      major pathway of Abeta toxicity in vivo, or a pathway that crucially impinges on
      it, may depend on cleavage of APP at Asp664. Since young PDAPP(D664A) mice showed
      an akinetic phenotype when first required to swim, we trained a 3-month-old (mo)
      cohort to criterion (normal swimming), and briefly exposed it to the Morris water
      maze (MWM) environment prior to training at 7 mo, to avoid potentially
      confounding effects of the akinetic phenotype in MWM studies. Prior experience
      decreased floating in PDAPP(D664A) mice but not in PDAPP nor in non-Tg groups.
      While learning was restored in experienced PDAPP(D664A) mice, it was
      indistinguishable from both non-Tg as well as from PDAPP mice in naive
      PDAPP(D664A) animals. Floating did not correlate with worse performance in naive
      PDAPP(D664A) mice, suggesting that the contribution of prior experience to
      improved performance is related to its cognitive effects but not to non-cognitive
      components of behaviour. Our results suggest that early experience reduces the
      contribution of non-cognitive components of behaviour to performance, and may
      contribute to the restoration of learning at later ages in PDAPP(D664A) mice.

PMID- 19751770
TI  - Mentally represented motor actions in normal aging: III. Electromyographic
      features of imagined arm movements.
AB  - Motor imagery is a cognitive process during which subjects mentally simulate
      movements without actually performing them. Here, we investigated the temporal
      and electromyographic (EMG) features of imagined arm movements in healthy elderly
      adults. Twelve young (mean age: 24.0+/-1.3 years) and 12 elderly (mean age:
      67.0+/-4.5 years) participants executed and mentally simulated, with their right
      and left arms and as fast and as accurately as possible, arm pointing movements
      between three targets located in the frontal plane. We used the mental
      chronometry paradigm as an indicator of the accuracy of the motor imagery process
      (i.e. isochrony between executed and imagined movements) and the EMG activity of
      four arm muscles (anterior deltoid, posterior deltoid, biceps brachii, triceps
      brachii) during imagined actions as an indicator of the ability to generate
      purely mental actions. Our findings indicated that young and elderly participants
      mentally simulated arm movements without activating (i.e. above the baseline
      level) the muscles of the right or the left arm which are involved in the
      execution of the same movements. This finding suggests that young and, notably,
      elderly adults are able to generate covert actions without any overt component.
      However, we found that motor imagery accuracy (i.e. the temporal correspondence
      between executed and imagined movements) was significantly deteriorated in
      elderly adults. We suggest that elderly adults use efferent copies of motor
      commands to generate motor representations; however, this ability is
      progressively deteriorated in the aging brain. Therefore, we propose using motor
      imagery cautiously for motor rehabilitation in the elderly.

PMID- 19751771
TI  - Sensory and motor aspects of addiction.
AB  - Research on the psychological and neuronal underpinnings of addiction has
      concentrated mostly on affective, motivational, learning, and executive processes
      and the brain regions subserving these functions. In contrast, sensory and motor
      aspects of addiction have largely been neglected even though they may be highly
      relevant for the development and preservation of addiction. The aim of the
      present review is to emphasize the significance of sensory and motor processes
      for the better understanding and treatment of addiction. We focus on research
      investigating substance-related addictions and on brain imaging studies in humans
      that have assessed the contribution of cortical and cerebellar systems to sensory
      and motor mechanisms of addiction. Activations of sensory and motor brain regions
      in response to drug-associated cues can predict relapse and correlate with
      craving, severity of dependence and automatized behavioral reactions towards drug
      related stimuli. We propose a model of how sensory and motor processes might be
      involved in the different stages of addiction.

PMID- 19751772
TI  - SPFH1 and SPFH2 mediate the ubiquitination and degradation of inositol 1,4,5
      trisphosphate receptors in muscarinic receptor-expressing HeLa cells.
AB  - Inositol 1,4,5-trisphosphate (IP(3)) receptors are endoplasmic reticulum (ER)
      membrane calcium channels that, upon activation, become substrates for the ER
      associated degradation (ERAD) pathway. While it is clear that IP(3) receptors are
      polyubiquitinated and are transferred to the proteasome by a p97-based complex,
      currently very little is known about the proteins that initially select activated
      IP(3) receptors for ERAD. Here, we have transfected HeLa cells to stably express
      m3 muscarinic receptors to allow for the study of IP(3) receptor ERAD in this
      cell type, and show that IP(3) receptors are polyubiquitinated and then degraded
      by the proteasome in response to carbachol, a muscarinic agonist. In seeking to
      identify proteins that mediate IP(3) receptor ERAD we found that both SPFH1 and
      SPFH2 (also known as erlin 1 and erlin 2), which exist as a hetero-oligomeric
      complex, rapidly associate with IP(3) receptors in a manner that precedes
      polyubiquitination and the association of p97. Suppression of SPFH1 and SPFH2
      expression by RNA interference markedly inhibited carbachol-induced IP(3)
      receptor polyubiquitination and degradation, but did not affect carbachol-induced
      calcium mobilization or IkappaBalpha processing, indicating that the SPFH1/2
      complex is a key player in IP(3) receptor ERAD, acting at a step after IP(3)
      receptor activation, but prior to IP(3) receptor polyubiquitination. Suppression
      of SPFH1 and SPFH2 expression had only slight effects on the turnover of some
      exogenous model ERAD substrates, and had no effect on sterol-induced ERAD of
      endogenous 3-hydroxy-3-methylglutaryl-CoA reductase. Overall, these studies show
      that m3 receptor-expressing HeLa cells are a valuable system for studying IP(3)
      receptor ERAD, and suggest that the SPFH1/2 complex is a factor that selectively
      mediates the ERAD of activated IP(3) receptors.

PMID- 19751773
TI  - Decreased cofilin1 expression is important for compaction during early mouse
      embryo development.
AB  - Compaction, occurring at the eight-cell stage of mouse development, is the
      process of cell flattening and polarization by which cellular asymmetry is first
      established. During this process many molecules and organelles undergo polarized
      distribution, but the cytoskeletal basis for these distribution specifications
      remains to be explored. The present study focused on cofilin1, an actin-binding
      protein that depolymerizes actin filaments. We showed that cofilin1 expression
      decreased at the compaction stage, and that down-regulation of cofilin1
      expression by siRNA microinjection accelerated compaction. Continuous observation
      using time-lapse video miscroscopy confirmed these findings. That is, the
      embryonic cells microinjected with anti-cofilin1 antibody exhibit earlier
      adherence properties compared to uninjected cells. Pronuclear microinjection of a
      site-directed mutated cofilin1 plasmid, in which cofilin1 is sustained in its
      active form produced embryos with blastomeres that did not adhere, suggesting
      that inactivation of cofilin1 is critical for cell flattening and adherence.
      Fluorescein-phalloidin staining indicated that decreased cofilin1 expression
      promoted the formation of the apical pole, which is a marker for polarity.
      Scanning electron microscopy results demonstrated the appearance of microvilli on
      the outer face of blastomeres in cofilin1 knockdown embryos. Our results suggest
      that cofilin1 plays an important role in cortical cytoplasmic organization during
      embryo compaction.

PMID- 19751774
TI  - Visfatin through STAT3 activation enhances IL-6 expression that promotes
      endothelial angiogenesis.
AB  - Signal transducer and activator of transcription 3 (STAT3) acts as a mediator and
      biomarker in endothelial activation. We have recently shown that a novel
      adipokine visfatin promotes endothelial angiogenesis. The present study was to
      determine whether visfatin affects STAT3 activity and to explore the potential
      target gene(s). Here, we found that visfatin induced the activation of STAT3, as
      characterized by increased tyrosine phosphorylation, nuclear translocation, and
      DNA-binding activity in human endothelial cells. In addition, visfatin
      significantly upregulated mRNA and protein levels of endothelial interleukin-6
      (IL-6), which was blocked by a specific inhibitor of STAT3 signaling and by the
      transfection of siRNA specific for STAT3. Furthermore, visfatin-induced
      angiogenesis was reduced by the inhibition of STAT3 signaling or neutralization
      of IL-6 function, as measured by tube formation, rat aortic ring assay, and mouse
      Matrigel plug assay. Taken together, our results provide the first example of
      STAT3-dependent endothelial IL-6 induction by visfatin and of the role of IL-6 in
      mediating visfatin-induced angiogenesis.

PMID- 19751775
TI  - Flow cytometric analysis of benthic prokaryotes attached to sediment particles.
AB  - Appropriate detachment treatments are required to analyze prokaryotes associated
      with streambed sediments by flow cytometry. Using our previously optimized
      protocol, two groups of cells exhibiting different nucleic acid contents were
      easily detectable. However, the Nucleic Acid Double Staining assay proved that
      detachment procedures negatively affect the cell membrane integrity.

PMID- 19751776
TI  - Sequence effects in the Go/NoGo task: inhibition and facilitation.
AB  - Facilitation and inhibition are asymmetric aspects of attention that
      differentially affect response times (RTs), accuracy and neuroelectric activity
      in many experimental tasks. Both vary as a function of stimulus context, with
      stimulus repetitions, for example, often resulting in facilitation in terms of
      speed, accuracy or reduced neural activity. Although inhibition has been
      extensively studied in the Go/NoGo task, facilitation has been overlooked. Twenty
      healthy adults performed an adapted Go/NoGo task which manipulated levels of
      facilitation and inhibition. Event-related potential (ERP) and behavioural
      measures were averaged according to preceding stimulus sequences. Established
      Go/NoGo effects for N2 and P3 components were replicated. Behavioural and ERP
      measures, however, showed strong sequence effects. Correlates of facilitation
      included reduced P1 and N1 latencies, and topographic effects in P1, to Go
      stimulus repetitions. Manipulations of inhibitory load through increasing Go
      before NoGo stimuli resulted in incremental increases in N1, P2 and N2 latencies.
      Several additional ERP and RT measures showed quadratic effects, with indications
      of facilitation or inhibition which reversed towards the end of longer stimulus
      trains. The results suggest that both facilitatory and inhibitory processes
      underlie performance in the Go/NoGo task. As Go stimuli are typically more
      frequently repeated than NoGo stimuli, the two processes may be confounded when
      sequence effects are not considered. Additionally, analysing stimuli by context
      indicates that the timing of the Go-P3 latency is closely related to responses,
      and the prolongation of N1, P2 and N2 with increasing difficulty of inhibition
      supports a possible relation of these components to inhibition.

PMID- 19751777
TI  - Nanoparticle-mediated combination chemotherapy and photodynamic therapy overcomes
      tumor drug resistance.
AB  - Tumor drug resistance significantly limits the success of chemotherapy in the
      clinic. Tumor cells utilize multiple mechanisms to prevent the accumulation of
      anticancer drugs at their intracellular site of action. In this study, we
      investigated the anticancer efficacy of doxorubicin in combination with
      photodynamic therapy using methylene blue in a drug-resistant mouse tumor model.
      Surfactant-polymer hybrid nanoparticles formulated using an anionic surfactant,
      Aerosol-OT (AOT), and a naturally occurring polysaccharide polymer, sodium
      alginate, were used for synchronized delivery of the two drugs. Balb/c mice
      bearing syngeneic JC tumors (mammary adenocarcinoma) were used as a drug
      resistant tumor model. Nanoparticle-mediated combination therapy significantly
      inhibited tumor growth and improved animal survival. Nanoparticle-mediated
      combination treatment resulted in enhanced tumor accumulation of both doxorubicin
      and methylene blue, significant inhibition of tumor cell proliferation, and
      increased induction of apoptosis. These data suggest that nanoparticle-mediated
      combination chemotherapy and photodynamic therapy using doxorubicin and methylene
      blue has significant therapeutic potential against drug-resistant tumors.

PMID- 19751778
TI  - Shielding the cationic charge of nanoparticle-formulated dermal DNA vaccines is
      essential for antigen expression and immunogenicity.
AB  - Nanoparticle-formulated DNA vaccines hold promise for the design of in vivo
      vaccination platforms that target defined cell types in human skin. A variety of
      DNA formulations, mainly based on cationic liposomes or polymers, has been
      investigated to improve transfection efficiency in in vitro assays. Here we
      demonstrate that formulation of DNA into both liposomal and polymeric cationic
      nanoparticles completely blocks vaccination-induced antigen expression in mice
      and ex vivo human skin. Furthermore, this detrimental effect of cationic
      nanoparticle formulation is associated with an essentially complete block in
      vaccine immunogenicity. The blocking of DNA vaccine activity may be explained by
      immobilization of the nanoparticles in the extracellular matrix, caused by
      electrostatic interactions of the cationic nanoparticles with negatively charged
      extracellular matrix components. Shielding the surface charge of the
      nanoparticles by PEGylation improves in vivo antigen expression more than 55
      fold. Furthermore, this shielding of cationic surface charge results in antigen
      specific T cell responses that are similar as those induced by naked DNA for the
      two lipo- and polyplex DNA carrier systems. These observations suggest that
      charge shielding forms a generally applicable strategy for the development of
      dermally applied vaccine formulations. Furthermore, the nanoparticle formulations
      developed here form an attractive platform for the design of targeted
      nanoparticle formulations that can be utilized for in vivo transfection of
      defined cell types.

PMID- 19751779
TI  - The 14th International Symposium on Recent Advances in Drug Delivery Systems,
      February 15-18, 2009, Salt Lake City, UT, USA.

PMID- 19751780
TI  - Protein bioactivity and polymer orientation is affected by stabilizer
      incorporation for double-walled microspheres.
AB  - Double-walled microspheres present an improved drug delivery technique for
      sustained release of encapsulated substrates. In this study, the release kinetics
      and biological activity of lysozyme was analyzed from microspheres comprised of
      poly(lactic-co-glycolic acid) (PLGA) and poly(L-lactide) (PLLA). In addition,
      coencapsulation of the anionic surfactant, docusate sodium salt (AOT), was
      investigated as a method of decreasing protein denaturation during microsphere
      fabrication. Herein, we show that through the inclusion of AOT, the capacity for
      two chemically similar polymers to phase separate and form double-walled (DW)
      microspheres is impaired leading to unique protein release kinetics.
      Additionally, we present the time period over which our released enzyme,
      lysozyme, remains biologically active. The consequences of AOT on protein
      bioactivity are also assessed and provide strong implications for the importance
      of appropriate stabilizer analysis in future studies involving drug co
      encapsulates in polymer based microsphere systems.

PMID- 19751781
TI  - When weight management lasts. Lower perceived rule complexity increases
      adherence.
AB  - Maintaining behavior change is one of the major challenges in weight management
      and long-term weight loss. We investigated the impact of the cognitive complexity
      of eating rules on adherence to weight management programs. We studied whether
      popular weight management programs can fail if participants find the rules too
      complicated from a cognitive perspective, meaning that individuals are not able
      to recall or process all required information for deciding what to eat. The
      impact on program adherence of participants' perceptions of eating rule
      complexity and other behavioral factors known to influence adherence (including
      previous weight management, self-efficacy, and planning) was assessed via a
      longitudinal online questionnaire given to 390 participants on two different
      popular weight management regimens. As we show, the regimens, Weight Watchers and
      a popular German recipe diet (Brigitte), strongly differ in objective rule
      complexity and thus their cognitive demands on the dieter. Perceived rule
      complexity was the strongest factor associated with increased risk of quitting
      the cognitively demanding weight management program (Weight Watchers); it was not
      related to adherence length for the low cognitive demand program (Brigitte).
      Higher self-efficacy generally helped in maintaining a program. The results
      emphasize the importance of considering rule complexity to promote long-term
      weight management.

PMID- 19751782
TI  - Young children's dietary habits and associations with the mothers' nutritional
      knowledge and attitudes.
AB  - The study investigates the dietary habits of Flemish preschoolers and
      associations of these habits with both sociodemographic characteristics and the
      mother's nutritional knowledge and attitudes. A sample of 862 parents of
      preschoolers from 56 schools completed a questionnaire including sociodemographic
      characteristics, a food-frequency questionnaire to assess children's dietary
      intake, and a nutritional knowledge-and-attitude questionnaire. Regression
      analysis showed a lower dietary adequacy in children of mothers with low and
      medium level of education, medium-ranked occupation, and lower levels of both
      nutritional knowledge and food-related health attitude. The highest excess score
      (representing items that should be avoided or moderated) was found in children of
      mothers with low education level, without a job, with three or more children, of
      age less than 30 years, and possessing lower levels of nutritional knowledge and
      attitude scores for health and taste. The associations of the dietary adequacy
      and excess scores with sociodemographic background can help practitioners to
      develop better-tailored nutrition interventions. The associations with the
      mothers' nutritional knowledge and attitudes support the inclusion of knowledge
      and attitudes in dietary interventions.

PMID- 19751783
TI  - Ghrelin vaccination decreases plasma MCP-1 level in LDLR(-/-)-mice.
AB  - Ghrelin is a novel peptide hormone having growth hormone releasing activity and
      many endocrine and metabolic functions. In rats and pigs, ghrelin immunizations
      have recently been shown to induce an antibody response against ghrelin
      simultaneously with a decrease in body weight gain. Our aim was to test the role
      of ghrelin immunization on atherosclerosis and weight gain in mice. LDLR(-/-)
      mice (n=36) were immunized with ghrelin-PADRE, PADRE alone and PBS and then
      placed on a high fat diet for 22 weeks. Weight gain and food intake were followed
      throughout the study. Acylated and total ghrelin, cytokines and MCP-1 were
      analyzed from plasma using commercial kits. Stomach ghrelin was assessed using
      qRT-PCR and immunohistochemistry. Atherosclerosis was determined from aorta and
      cross-sections at the end of study. Mice immunized with ghrelin-PADRE developed
      high plasma IgG titers to ghrelin simultaneously with a significant increase in
      plasma acylated and total ghrelin levels. Plasma MCP-1 levels decreased in mice
      immunized with ghrelin-PADRE compared to mice immunized with PADRE and PBS. There
      were no differences in atherosclerosis determined from aorta and cross-sections
      as well as in body weights and food intake in LDLR(-/-)-mice between the
      different immunization groups. Our data indicates that ghrelin-PADRE vaccination
      induces a strong exclusive IgG response to ghrelin and increases plasma acylated
      and total ghrelin levels in mice. Ghrelin vaccination decreases plasma MCP-1
      levels even though no effects on developing signs of atherosclerosis or weight
      gain in mice were observed.

PMID- 19751784
TI  - CD147, a gamma-secretase associated protein is upregulated in Alzheimer's disease
      brain and its cellular trafficking is affected by presenilin-2.
AB  - Gamma-secretase activity has been extensively investigated due to its role in
      Alzheimer's disease. Here, we studied the association of CD147, a transmembrane
      glycoprotein belonging to the immunoglobulin family, with gamma-secretase and its
      expression in Alzheimer's disease and control tissues. Subcellular fractionation
      of postmitochondrial supernatant from rat brain on step iodixanol gradient in
      combination with co-immunoprecipitation using an anti-nicastrin antibody showed
      association of limited amount of CD147 to gamma-secretase. By immunoblotting of
      postnuclear pellets from Alzheimer's disease and control human brain tissues we
      showed that CD147 with molecular weight 75 kDa is upregulated in frontal cortex
      and thalamus of the Alzheimer's disease brains. Immunohistochemistry of brain
      tissues from Alzheimer's disease and control revealed specific upregulation of
      CD147 in neurons, axons and capillaries of Alzheimer's disease frontal cortex and
      thalamus. The effect of presenilin-1 and -2, which are the catalytic subunits of
      gamma-secretase, on CD147 expression and subcellular localization was analyzed by
      confocal microscopy in combination with flow cytometry and showed that PS2
      affected the subcellular localization of CD147 in mouse embryonic fibroblast
      cells. We suggest that a small fraction of CD147 present in the brain is
      associated with the gamma-secretase, and can be involved in mechanisms
      dysregulated in Alzheimer's disease brain.

PMID- 19751785
TI  - Pharmacological characterization of glutamate Na+-independent transport in
      retinal cell cultures: implications in the glutathione metabolism.
AB  - L-glutamate is the primary excitatory neurotransmitter in the mammalian central
      nervous system (CNS). Mechanisms for the removal of glutamate are vital for
      maintaining normal function of retina. In the present study, using retinal cell
      cultures obtained from chick embryos, we characterize, pharmacologically, the
      presence of two glutamate transporter mechanisms, Na(+)-dependent and Na(+)
      independent uptake systems. Na(+)-independent uptake system seems to present
      characteristics related to system x(CG)(-) (cystine-glutamate exchanger) that in
      the current work demonstrated highlighted contribution to the glutamate transport
      in retina, which is not observed in other tissues. Our results showed that
      glutamate shares x(CG)(-) system with another amino acid, L-cysteine, suggesting
      the possible involvement of this component in processes related to the release of
      the glutathione antioxidant molecule. Furthermore, cysteine uptake by Na(+)
      independent transport appears to be more evident in glial cell cultures than in
      neuronal cell cultures. So, Na(+)-independent transport system seems to have
      other functions besides amino acid transport, demonstrating a physiological role
      in modulating cell redox status.

PMID- 19751786
TI  - Adverse events associated with the use of insect repellents containing N,N
      diethyl-m-toluamide (DEET).
AB  - DEET is the major component of most topically applied insect repellents used in
      the US. The DEET Registry is a post-marketing surveillance system to provide
      systematic and detailed information about medical events temporally associated
      with DEET use. From 1995 to 2001, 296 moderate and major severity cases were
      included in the DEET Registry. Of these, 36 (14.5%) cases were deemed to be
      probably and 157 (65%) cases possibly related to DEET exposure. Insufficient data
      prevented determination of causality in the remaining 49 (20.2%) cases. Forty-one
      percent of the cases were in children 19 or younger. Forty-two percent of
      children experienced a seizure of moderate or major severity. The widely variable
      spectrum of other neurological symptoms reported in the Registry makes it
      unlikely they were due to one agent. People with an underlying neurological
      disorder were not disproportionately represented in the DEET Registry. Data
      showed no clear relationship between case severity and DEET concentration or
      concurrent use of common medicines. Recognizing the extensive use of DEET in the
      US and considering the information about the more serious adverse events
      described in the Registry, the risk of serious neurological events following the
      use of DEET repellents is quite low.

PMID- 19751787
TI  - Derivation of Biomonitoring Equivalents for di-n-butyl phthalate (DBP),
      benzylbutyl phthalate (BzBP), and diethyl phthalate (DEP).
AB  - Recent efforts worldwide have resulted in a growing database of measured
      concentrations of chemicals in blood and urine samples taken from the general
      population. However, few tools exist to assist in the interpretation of the
      measured values in a health risk context. Biomonitoring Equivalents (BEs) are
      defined as the concentration or range of concentrations of a chemical or its
      metabolite in a biological medium (blood, urine, or other medium) that is
      consistent with an existing health-based exposure guideline, and are derived by
      integrating available data on pharmacokinetics with existing chemical risk
      assessments. This study reviews available health-based exposure guidance values
      for di-n-butyl phthalate (DBP), benzylbutyl phthalate (BzBP), and diethyl
      phthalate (DEP) from Health Canada, the United States Environmental Protection
      Agency (U.S. EPA), the Agency for Toxic Substances and Disease Registry (ATSDR),
      and the European Food Safety Authority (EFSA). BE values corresponding to the
      oral reference dose (RfD), minimal risk level (MRL) or tolerable daily intake
      (TDI) estimates from these agencies were derived for each compound based on data
      on excretion fractions of key urinary metabolites. These values may be used as
      screening tools for evaluation of biomonitoring data for metabolites of these
      three phthalate compounds in the context of existing risk assessments and for
      prioritization of the potential need for additional risk assessment efforts for
      each of these compounds relative to other chemicals.

PMID- 19751788
TI  - Derivation of Biomonitoring Equivalents for cyfluthrin.
AB  - Recent efforts worldwide have resulted in a growing database of measured
      concentrations of chemicals in blood and urine samples taken from the general
      population. However, few tools exist to assist in the interpretation of the
      measured values in a health risk context. Biomonitoring Equivalents (BEs) are
      defined as the concentration or range of concentrations of a chemical or its
      metabolite in a biological medium (blood, urine, or other medium) that is
      consistent with an existing health-based exposure guideline, and are derived by
      integrating available data on pharmacokinetics with existing chemical risk
      assessments. This study reviews available health-based exposure guidance values
      for cyfluthrin from Health Canada, the United States Environmental Protection
      Agency (USEPA), and the World Health Organization/Food and Agriculture
      Organization. BE values corresponding to the oral reference dose (RfD), or
      acceptable daily intake (ADI) estimates from these agencies were derived based on
      data on excretion fractions of the urinary metabolite 4-fluoro-3-phenoxybenzoic
      acid (FPBA), which is a metabolite specific to cyfluthrin. These values may be
      used as screening tools for evaluation of biomonitoring data for cyfluthrin as
      the metabolite FPBA in the context of existing risk assessments and for
      prioritization of the potential need for additional risk assessment efforts for
      cyfluthrin relative to other chemicals.

PMID- 19751789
TI  - Derivation of Biomonitoring Equivalents for di(2-ethylhexyl)phthalate (CAS No.
      117-81-7).
AB  - Recent efforts worldwide have resulted in a growing database of measured
      concentrations of chemicals in blood and urine samples taken from the general
      population. However, few tools exist to assist in the interpretation of the
      measured values in a health risk context. Biomonitoring Equivalents (BEs) are
      defined as the concentration or range of concentrations of an environmental
      chemical or its metabolite in a biological medium (blood, urine, or other medium)
      that is consistent with an existing health-based exposure guideline, and are
      derived by integrating available data on pharmacokinetics with existing chemical
      risk assessments. This study reviews available health-based exposure guidance
      values for di(2-ethylhexyl)phthalate (DEHP) from Health Canada, the United States
      Environmental Protection Agency (U.S. EPA), the Agency for Toxic Substances and
      Disease Registry (ATSDR), the European Chemicals Bureau (ECB), and the European
      Food Safety Authority (EFSA). BE values corresponding to the oral reference dose
      (RfD), minimal risk level (MRL) or tolerable daily intake (TDI) estimates from
      these agencies were derived based on data on excretion fractions of key urinary
      metabolites. BE values based on the sum of three, four, and five of the most
      predominant and commonly-measured metabolites of DEHP are presented. These values
      may be used as screening tools for evaluation of biomonitoring data for DEHP
      metabolites in the context of existing risk assessments and for prioritization of
      the potential need for additional risk assessment efforts for DEHP relative to
      other chemicals.

PMID- 19751790
TI  - Differentiation of first-episode schizophrenia patients from healthy controls
      using ROI-based multiple structural brain variables.
AB  - BACKGROUND: Brain morphometric measures from magnetic resonance imaging (MRI)
      have not been used to discriminate between first-episode patients with
      schizophrenia and healthy subjects. METHODS: Magnetic resonance images were
      acquired from 34 (17 males, 17 females) first-episode schizophrenia patients and
      48 (24 males, 24 females) age- and parental socio-economic status-matched healthy
      subjects. Twenty-nine regions of interest (ROI) were measured on 1-mm-thick
      coronal slices from the prefrontal and central parts of the brain. Linear
      discriminant function analysis was conducted using standardized z scores of the
      volumes of each ROI. RESULTS: Discriminant function analysis with cross
      validation procedures revealed that brain anatomical variables correctly
      classified 75.6% of male subjects and 82.9% of female subjects, respectively. The
      results of the volumetric comparisons of each ROI between patients and controls
      were generally consistent with those of the previous literature. CONCLUSIONS: To
      our knowledge, this study provides the first evidence of MRI-based successful
      classification between first-episode patients with schizophrenia and healthy
      controls. The potential of these methods for early detection of schizophrenia
      should be further explored.

PMID- 19751791
TI  - Consciously-perceived generalized epileptiform discharges in a man with
      schizoaffective disorder.

PMID- 19751792
TI  - Hyperglycaemia in an 11-year-old girl after quetiapine treatment.

PMID- 19751793
TI  - Effect of arachidonyl-2'-chloroethylamide, a selective cannabinoid CB1 receptor
      agonist, on the protective action of the various antiepileptic drugs in the mouse
      maximal electroshock-induced seizure model.
AB  - The aim of this study was to determine the influence of arachidonyl-2'
      chloroethylamide (ACEA - a highly selective cannabinoid type 1 [CB1] receptor
      agonist) on the protective action and acute adverse effects of carbamazepine,
      lamotrigine, oxcarbazepine, phenobarbital, phenytoin, and topiramate in the
      maximal electroshock seizure model and chimney test in mice. Tonic hind limb
      extension (seizure activity) was evoked in adult male albino Swiss mice by a
      current (sine-wave, 25 mA, 500 V, 50 Hz, 0.2s stimulus duration) delivered via
      auricular electrodes. Acute adverse-effect profiles of the studied antiepileptic
      drugs with respect to motor coordination was assessed in the chimney test.
      Additionally, long-term memory and skeletal muscular strength were measured along
      with free plasma (non-protein bound) and total brain antiepileptic drug
      concentrations. To inhibit the rapid metabolic degradation of ACEA by the fatty
      acid amide hydrolase, phenylmethylsulfonyl fluoride (PMSF) was used at a constant
      ineffective dose of 30 mg/kg. Results indicate that ACEA (2.5 mg/kg, i.p.) co
      administered with PMSF (30 mg/kg, i.p.), significantly enhanced the
      anticonvulsant activity of phenobarbital, but not that of carbamazepine,
      lamotrigine, oxcarbazepine, phenytoin, or topiramate in the maximal electroshock
      seizure test in mice. Moreover, ACEA (2.5 mg/kg) with PMSF (30 mg/kg) had no
      significant impact on the acute adverse effects of all examined antiepileptic
      drugs in the chimney test in mice. The protective index values (as quotients of
      the respective TD(50) and ED(50) values denoted from the chimney and maximal
      electroshock seizure tests, respectively) for the combinations of ACEA (2.5
      mg/kg) and PMSF (30 mg/kg) with carbamazepine, oxcarbazepine, phenobarbital, and
      topiramate were greater than those denoted for the antiepileptic drugs
      administered alone. Only, the protective index values for the combination of ACEA
      (2.5 mg/kg) and PMSF (30 mg/kg) with lamotrigine and phenytoin were lower than
      those determined for the antiepileptic drugs administered alone. Pharmacokinetic
      experiments revealed that ACEA (2.5 mg/kg) and PMSF (30 mg/kg) affected neither
      free plasma (non-protein bound) nor total brain concentrations of phenobarbital
      in mice. Moreover, ACEA and PMSF in combination with carbamazepine, lamotrigine,
      oxcarbazepine, phenobarbital, phenytoin, and topiramate did not alter long-term
      memory or skeletal muscular strength in experimental animals. In conclusion, the
      enhanced anticonvulsant action of phenobarbital by ACEA and PMSF, lack of
      pharmacokinetic interaction and no acute adverse effects between the examined
      compounds, make the combination of ACEA and PMSF with phenobarbital of pivotal
      importance for further experimental and clinical studies. The combinations of
      ACEA and PMSF with carbamazepine, lamotrigine, oxcarbazepine, phenytoin, and
      topiramate are neutral from a preclinical viewpoint.

PMID- 19751794
TI  - Depression during pregnancy and postpartum: contribution of stress and ovarian
      hormones.
AB  - Depression is the most common psychiatric disease among women, exhibiting a
      prevalence which is 2-3x higher than in men. The postpartum period is considered
      the time of greatest risk for women to develop major depression and postpartum
      depression affects approximately 15% of women. A dysregulation of the
      hypothalamus-pituitary-adrenal (HPA) axis is the most prominent endocrine change
      seen in depression and normalization of the HPA axis is a major target of recent
      therapies. Females exhibit different stress sensitivities than males which might
      contribute to their increased vulnerability for depression. Maternal stress or
      depression during pregnancy and/or postpartum is particularly concerning as early
      developmental influences can affect the maturation of the offspring as well as
      the mental health of the mother. Despite the urgent need for more information on
      depression in females, especially during pregnancy and postpartum, most animal
      models of depression have utilized only males. Given the sex differences in
      incidence of depression and treatment, it is vitally important to create or
      validate animal models of depression in females. This review will focus on the
      association between stress, glucocorticoids and depression in humans, with a
      special focus on depression in women during pregnancy and postpartum and on
      animal models of postpartum depression and the consequences for the offspring.

PMID- 19751795
TI  - Microgram-order ammonium perfluorooctanoate may activate mouse peroxisome
      proliferator-activated receptor alpha, but not human PPARalpha.
AB  - Perfluorooctanoic acid (PFOA) is a ligand for peroxisome proliferator-activated
      receptor (PPAR) alpha, which exhibits marked species differences in expression
      and function, especially between rodents and humans. We investigated the
      functional difference in PFOA response between mice and humans, using a humanized
      PPARalpha transgenic mouse line. Three genotyped mice, 129/Sv wild-type
      (mPPARalpha), Pparalpha-null mice and humanized PPARalpha (hPPARalpha) mice (8
      week-old males) were divided into three groups: the first was treated with water
      daily for 2 weeks by gavage (control group), and the remaining two groups were
      treated with 0.1 and 0.3mg/kg ammonium perflurooctanate (APFO), respectively, for
      2 weeks by gavage. The APFO dosages used did not influence the plasma
      triglyceride or total cholesterol levels in any mouse line, but the high dose
      increased both hepatic lipid levels only in mPPARalpha mice. APFO increased mRNA
      and/or protein levels of PPARalpha target genes cytochrome P450 Cyp4a10,
      peroxisomal thiolase and bifunctional protein only in the liver of mPPARalpha
      mice, but not in Pparalpha-null or hPPARalpha mice. This chemical also increased
      expression of mitochondrial very long chain acyl-CoA dehydrogenase only in the
      liver of mPPARalpha mice. Taken together, human PPARalpha may be less responsive
      to PFOA than that of mice when a relatively low dose is applied. This information
      may be very valuable in considering whether PFOA influences the lipid metabolism
      in humans.

PMID- 19751796
TI  - FAD binding in glycine oxidase from Bacillus subtilis.
AB  - The apoprotein of the FAD-containing flavoenzyme glycine oxidase from Bacillus
      subtilis was obtained at pH 8.5 by dialyzing the holoenzyme against 2 M KBr in
      0.25 M Tris-HCl and 20% glycerol. The apoprotein of glycine oxidase shows high
      protein fluorescence, high exposure of hydrophobic surfaces, and low temperature
      stability as compared to the holoenzyme. The isolated apoprotein species is
      present in solution as a monomer which rapidly recovers its tertiary structure
      and converts into the tetrameric holoenzyme following incubation with free FAD.
      The reconstitution process follows a particular two-stage process; the spectral
      properties of the reconstituted holoenzyme were virtually indistinguishable from
      those observed with native glycine oxidase, while the activity was only partially
      (50%) recovered. The urea-induced unfolding process of glycine oxidase can be
      considered as a two-step (three-state) process: the presence of intermediate(s)
      in the unfolding process of the holoenzyme at approximately 2 M urea is evident
      in the changes of the flavin fluorescence intensity and can be also inferred from
      the different urea sensitivities of the spectral probes used. On the other hand,
      only a single transition at approximately 4.5 M urea concentration is observed
      for the apoprotein form. The chemical denaturation of glycine oxidase holoenzyme
      is partially reversible (e.g., no activity is recovered when starting the
      refolding from 4 M urea-denatured holoprotein). Finally, the introduction by site
      directed mutagenesis of residues corresponding to those involved in the covalent
      link with FAD in the related flavoenzyme monomeric sarcosine oxidase failed to
      convert glycine oxidase into a covalent flavoprotein. These investigations show
      that the consequences of FAD binding for the stability and folding process
      distinguish glycine oxidase from enzymes active on similar compounds.

PMID- 19751797
TI  - An event-related potential study on exposure therapy for patients suffering from
      spider phobia.
AB  - The present event-related potential (ERP) study investigated electrocortical
      changes related to cognitive behavior therapy (CBT) in spider phobic females.
      Forty-five patients and twenty non-phobic women were presented with phobia
      relevant, generally fear-inducing, disgust-inducing and affectively neutral
      pictures in a first EEG session. Phobic patients were randomly assigned to either
      a therapy (TG) or a waiting-list (WG) group. EEG measurement was repeated after
      CBT or a waiting period. ERPs were extracted in the time windows 340-500ms
      (P300), 550-770ms (late positive potential (LPP), early LPP) and 800-1500ms (late
      LPP). Relative to controls, untreated phobics showed enhanced amplitudes of P300
      and early LPP in response to spider pictures. This most likely reflects the
      emotional significance of the phobic stimulus, which automatically draws
      attention. The therapy effect consisted of a significant enhancement of late LPP
      amplitudes in response to spider pictures. Results are discussed in terms of
      reduced attentional avoidance.

PMID- 19751798
TI  - Auditory stream segregation in children with Asperger syndrome.
AB  - Individuals with Asperger syndrome (AS) often have difficulties in perceiving
      speech in noisy environments. The present study investigated whether this might
      be explained by deficient auditory stream segregation ability, that is, by a more
      basic difficulty in separating simultaneous sound sources from each other. To
      this end, auditory event-related brain potentials were recorded from a group of
      school-aged children with AS and a group of age-matched controls using a paradigm
      specifically developed for studying stream segregation. Differences in the
      amplitudes of ERP components were found between groups only in the stream
      segregation conditions and not for simple feature discrimination. The results
      indicated that children with AS have difficulties in segregating concurrent sound
      streams, which ultimately may contribute to the difficulties in speech-in-noise
      perception.

PMID- 19751799
TI  - Reproducibility and usability of chronic virus infection model using agent-based
      simulation; comparing with a mathematical model.
AB  - We created agent-based models that visually simulate conditions of chronic viral
      infections using two software. The results from two models were consistent, when
      they have same parameters during the actual simulation. The simulation results
      comprise a transient phase and an equilibrium phase, and unlike the mathematical
      model, virus count transit smoothly to the equilibrium phase without overshooting
      which correlates with actual biology in vivo of certain viruses. We investigated
      the effects caused by varying all the parameters included in concept; increasing
      virus lifespan, uninfected cell lifespan, uninfected cell regeneration rate,
      virus production count from infected cells, and infection rate had positive
      effects to the virus count during the equilibrium period, whereas increasing the
      latent period, the lifespan-shortening ratio for infected cells, and the cell
      cycle speed had negative effects. Virus count at the start did not influence the
      equilibrium conditions, but it influenced the infection development rate. The
      space size had no intrinsic effect on the equilibrium period, but virus count
      maximized when the virus moving speed was twice the space size. These agent-based
      simulation models reproducibly provide a visual representation of the disease,
      and enable a simulation that encompasses parameters those are difficult to
      account for in a mathematical model.

PMID- 19751800
TI  - Enhancing non-coding RNA information content with ADAR editing.
AB  - The depth and complexity of the non-coding transcriptome in nervous system
      tissues provides a rich substrate for adenosine de-amination acting on RNA
      (ADAR). Non-coding RNAs (ncRNAs) serve diverse regulatory and computational
      functions, coupling signal flow from the environment to evolutionarily coded
      analog and digital information elements within the transcriptome. We present a
      perspective of ADARs interaction with the non-coding transcriptome as a
      computational matrix, enhancing the information processing power of the cell,
      adding flexibility, rapid response, and fine tuning to critical pathways.
      Dramatic increases in ADAR activity during stress response and inflammation
      result in powerful information processing events that change the functional state
      of the cell. This review examines the pathways and mechanisms of ADAR interaction
      with the non-coding transcriptome, and their functional consequences for
      information processing in nervous system tissues.

PMID- 19751801
TI  - Telomerase in cancer immunotherapy.
AB  - Telomerase is a common hallmark of cancer. Recent studies have shown promising
      developments in anti-telomerase cancer immunotherapy, using human telomerase
      reverse transcriptase (hTERT) as a tumor antigen. Vaccination, using hTERT
      peptides or adoptive transfer of hTERT-specific cytotoxic T lymphocytes, induces
      augmented tumor regression. CD8+ cytotoxic T lymphocytes, against various hTERT
      peptides, lyse hTERT-expressing tumor cells from multiple tissue origins. CD4+
      helper T lymphocytes are also activated by peptides derived from hTERT. This
      article reviews the current and potential future applications of various hTERT
      peptide antigens as candidates for cancer vaccines, and explores the experimental
      challenges that needed to be faced to develop telomerase-based tumor vaccines to
      treat human cancer.

PMID- 19751802
TI  - Regulation of glutamatergic and GABAergic neurotransmission in the chick nucleus
      laminaris: role of N-type calcium channels.
AB  - Neurons in the chicken nucleus laminaris (NL), the third order auditory nucleus
      involved in azimuth sound localization, receive bilaterally segregated
      (ipsilateral vs contralateral) glutamatergic excitation from the cochlear nucleus
      magnocellularis and GABAergic inhibition from the ipsilateral superior olivary
      nucleus (SON). Here, I investigate the voltage-gated calcium channels (VGCCs)
      that trigger the excitatory and the inhibitory transmission in the NL. Whole-cell
      recordings were performed in acute brainstem slices. The excitatory transmission
      was predominantly mediated by N-type VGCCs, as the specific N-type blocker omega
      Conotoxin-GVIA (omega-CTx-GVIA, 1-2.5 microM) inhibited excitatory postsynaptic
      currents (EPSCs) by approximately 90%. Blockers for P/Q- and L-type VGCCs
      produced no inhibition, and blockade of R-type VGCCs produced a small inhibition.
      In individual cells, the effect of each VGCC blocker on the EPSC elicited by
      activation of the ipsilateral input was the same as that on the EPSC elicited by
      activation of the contralateral input, and the two EPSCs had similar kinetics,
      suggesting physiological symmetry between the two glutamatergic inputs to single
      NL neurons. The inhibitory transmission in NL neurons was almost exclusively
      mediated by N-type VGCCs, as omega-CTx-GVIA (1 microM) produced a approximately
      90% reduction of inhibitory postsynaptic currents, whereas blockers for other
      VGCCs produced no inhibition. In conclusion, N-type VGCCs play a dominant role in
      triggering both the excitatory and the inhibitory transmission in the NL, and the
      presynaptic VGCCs that mediate the two bilaterally segregated glutamatergic
      inputs to individual NL neurons are identical. These features may play a role in
      optimizing coincidence detection in NL neurons.

PMID- 19751803
TI  - Functional expression of two system A glutamine transporter isoforms in rat
      auditory brainstem neurons.
AB  - Glutamine plays multiple roles in the CNS, including metabolic functions and
      production of the neurotransmitters glutamate and GABA. It has been proposed to
      be taken up into neurons via a variety of membrane transport systems, including
      system A, which is a sodium-dependent electrogenic amino acid transporter system.
      In this study, we investigate glutamine transport by application of amino acids
      to individual principal neurons of the medial nucleus of the trapezoid body
      (MNTB) in acutely isolated rat brain slices. A glutamine transport current was
      studied in patch-clamped neurons, which had the electrical and pharmacological
      properties of system A: it was sodium-dependent, had a non-reversing current
      voltage relationship, was activated by proline, occluded by N
      (methylamino)isobutyric acid (MeAIB), and was unaffected by 2-aminobicyclo
      [2.2.1]-heptane-2-carboxylic acid (BCH). Additionally, we examined the expression
      of different system A transporter isoforms using immunocytochemical staining with
      antibodies raised against system A transporter 1 and 2 (SAT1 and SAT2). Our
      results indicate that both isoforms are expressed in MNTB principal neurons, and
      demonstrate that functional system A transporters are present in the plasma
      membrane of neurons. Since system A transport is highly regulated by a number of
      cellular signaling mechanisms and glutamine then goes on to activate other
      pathways, the study of these transporters in situ gives an indication of the
      mechanisms of neuronal glutamine supply as well as points of regulation of
      neurotransmitter production, cellular signaling and metabolism in the native
      neuronal environment.

PMID- 19751804
TI  - Functional difference of receptor-type protein tyrosine phosphatase zeta/beta
      isoforms in neurogenesis of hippocampal neurons.
AB  - Receptor-type protein tyrosine phosphatase zeta/beta (RPTPzeta) is a
      transmembrane chondroitin sulfate proteoglycan (CSPG) and has been shown to play
      crucial roles in controlling axonal growth and neuronal migration. The RPTPzeta
      has two transmembranous isoforms, shorter receptor form of RPTPzeta (sRPTPzeta)
      and full-length receptor form of RPTPzeta (fRPTPzeta), but no studies have been
      reported about functional difference of these two isoforms. In the present study,
      therefore, we examined whether or not two RPTPzeta isoforms have different role
      in controlling dendritic morphology and synaptic number in cultured hippocampal
      neurons using the quantitative morphometrical analysis. Confocal microscopic
      observation showed that the immunoreactivity of RPTPzeta was observed throughout
      cells such as axons, growth cones, and dendrites at the early stages of neuronal
      culture, while it was seen predominantly on dendrites at the late stages. Western
      blotting analysis revealed that fRPTPzeta was mainly expressed at the early
      stages of culture and both RPTPzeta isoforms were expressed at late stages of
      culture. The overexpression of sRPTPzeta in hippocampal neurons increased the
      dendritic arborization without altering the average length of dendritic branches,
      whereas that of fRPTPzeta decreased the dendritic arborization and increased the
      average length of dendritic branches. The RNA interference of fRPTPzeta
      expression increased the dendritic arborization without altering the average
      length of dendritic branches. The overexpression of fRPTPzeta decreased the
      density of hippocampal dendritic synapses, but that of sRPTPzeta had no effects.
      Pleiotrophin, a ligand for RPTPzeta to interfere the phosphatase activity,
      increased the density of hippocampal dendritic synapses. Thus, the present study
      demonstrates that two transmembranous RPTPzeta isoforms have different functions
      for regulating dendritogenesis and synaptogenesis.

PMID- 19751805
TI  - From the genome to the phenome and back: linking genes with human brain function
      and structure using genetically informed neuroimaging.
AB  - In recent years, an array of brain mapping techniques has been successfully
      employed to link individual differences in circuit function or structure in the
      living human brain with individual variations in the human genome. Several proof
      of-principle studies provided converging evidence that brain imaging can
      establish important links between genes and behaviour. The overarching goal is to
      use genetically informed brain imaging to pinpoint neurobiological mechanisms
      that contribute to behavioural intermediate phenotypes or disease states. This
      special issue on "Linking Genes to Brain Function in Health and Disease" provides
      an overview over how the "imaging genetics" approach is currently applied in the
      various fields of systems neuroscience to reveal the genetic underpinnings of
      complex behaviours and brain diseases. While the rapidly emerging field of
      imaging genetics holds great promise, the integration of genetic and neuroimaging
      data also poses major methodological and conceptual challenges. Therefore, this
      special issue also focuses on how these challenges can be met to fully exploit
      the synergism of genetically informed brain imaging.

PMID- 19751806
TI  - Synaptogenesis in the developing mouse visual cortex.
AB  - We used transmission electron microscopy to study ultrastructural changes
      accompanying synaptogenesis in the fetal and postnatal mouse visual cortex
      (primary visual cortex). Immunostaining and DiI diolistic assay were also
      employed in order to evaluate synaptophysin expression and dendritic spine
      development. Nascent synapses were seen as early as E15, although these were
      immature and were composed of a presumed presynaptic terminal with pleiomorphic
      vesicles in the vicinity of a partner cell body or projection. The postsynaptic
      plasmalemma remained unspecialized and the gap between pre- and post-synaptic
      plasmalemmas was only 5-10nm, significantly narrower than the mature synaptic
      cleft. With increasing age there was gradual thickening of both the pre- and post
      synaptic membranes, with widening of the synaptic cleft to 15-20 nm.
      Ultrastructurally mature synapses were not seen until P7; at this time both
      Gray's type I and II could be observed. Synaptogenesis correlated with the
      development of synaptic spines and synaptophysin expression. Because synapse
      maturation was synchronous with dendritic spine differentiation, synaptic
      specialization may be dependent on dendritic spine maturation and the expression
      of presynaptic vesicle components. In the meantime, the study also indicated that
      the synaptogenesis was connected with the development and maturation of
      neocortex.

PMID- 19751807
TI  - Evaluation of the protective effects of PACAP with cell-specific markers in
      ischemia-induced retinal degeneration.
AB  - Pituitary adenylate cyclase activating polypeptide (PACAP) is a neurotrophic and
      neuroprotective peptide that has been shown to exert protective effects in
      different neuronal injuries, such as traumatic brain injury, models of
      neurodegenerative diseases and cerebral ischemia. We have provided evidence that
      PACAP is neuroprotective in several models of retinal degeneration in vivo. In
      our previous studies we showed that PACAP treatment significantly ameliorated the
      damaging effects of permanent bilateral common carotid artery occlusion (BCCAO).
      In the present study cell-type-specific markers were used in the same models in
      order to further specify the protective effects of PACAP. In rats BCCAO led to
      severe degeneration of all retinal layers that was attenuated by PACAP (100 pmol)
      administered unilaterally immediately following BCCAO into the vitreous body of
      one eye. Retinas were processed for immunohistochemistry after 3 weeks.
      Immunolabeling was executed for vesicular glutamate transporter 1 (VGLUT 1),
      vesicular gamma-aminobutyric acid transporter (VGAT), protein kinase Calpha
      (PKCalpha), glial fibrillary acidic protein (GFAP) and calcium-binding proteins,
      such as calbindin, calretinin, parvalbumin. In BCCAO retinas, intensity of
      immunopositivity for all antisera was dramatically decreased, except in the case
      of GFAP. In PACAP-treated retinas, immunostaining was similar to that of the
      control animals. In summary, our study presented immunohistochemical
      identification of cell types sensitive to chronic retinal hypoperfusion and the
      protective effects of PACAP. This analysis revealed that the retinoprotective
      effects of PACAP are not phenotype-specific, but it rather influences general
      cytoprotective pathways irrespective of the neuronal subtypes in the retina
      subjected to chronic hypoperfusion.

PMID- 19751808
TI  - Reactive oxygen species scavenging activities and inhibition on DNA oxidative
      damage of dimeric compounds from the oxidation of (-)-epigallocatechin-3-O
      gallate.
AB  - The dimeric catechins dehydrotheasinensin A (2) and theacitrin C (3) were
      prepared from the oxidation of (-)-epigallocatechin-3-O-gallate (EGCG, 1), and
      their antioxidant activity was investigated using a chemiluminescence (CL) method
      in vitro. Both compounds showed significant inhibitory effects on reactive oxygen
      species (O(2)(-), H(2)O(2) and *OH) and DNA oxidative damage, with 2 being more
      potent than 3 and EGCG itself.

PMID- 19751809
TI  - A new steroidal saponin from the dried stems of Asparagus officinalis L.
AB  - Yamogenin II (1), a new steroidal saponin with a unique aglycone moiety, and
      (25S)-spirostan-5-ene-3beta-ol-3-O-alpha-L-rhamnopyranosyl-(1,2)-[alpha-L
      rhamnopyranosyl-(1,4)]-beta-D-glucopyranoside (2), were isolated from the dried
      stems of Asparagus officinalis L. The structure of 1 was assessed by
      spectroscopial analysis as (25S)-spirostan-5-ene-3beta,21-diol-3-O-alpha-L
      rhamnopyranosyl-(1,2)-[alpha-L-rhamnopyranosyl-(1,4)]-beta-D-glucopyranoside.

PMID- 19751810
TI  - Identification of Wnt4 as the ovary pathway gene and temporal disparity of its
      expression vis-a-vis testis genes in the garden lizard, Calotes versicolor.
AB  - Sex determination in the Indian garden lizard, Calotes versicolor, which lacks
      sex chromosomes and temperature-dependent sex determination, appears to be
      genically controlled, and previous studies have identified orthologues of Sox9,
      Dmrt1 and Androgen receptor (AR) as genes involved in testis differentiation in
      genetic males. In the pursuit of female pathway genes in this species, the
      present paper deals with the identification of Wnt4 and Dax1 genes in C.
      versicolor and their expression in embryonic gonad. CvDax1 is expressed
      throughout the development in certain embryos from day 5 onwards but shows no
      clear association with either testis or ovary. However, its preferred association
      with CvSox9 in early development and with CvWnt4 during later development
      suggests a role in the structuring of the gonads. CvWnt4 shows little expression
      in early development. It expresses prominently from day 20 onwards, and almost
      exclusively in those embryos that do not express CvSox9, demonstrating that
      CvWnt4 is the ovary differentiation gene in this species. This evidence leads us
      to suggest that temporal distinction of expression of ovary-specific (day 20
      onwards) and testis-specific (day 5 onwards) genes could be an important part of
      the process of sex determination in C. versicolor. Taken together, the mechanism
      of sex determination in C. versicolor appears closer to the CSD in mammals than
      that in the ESD reptiles and birds.

PMID- 19751811
TI  - Clan CD of cysteine peptidases as an example of evolutionary divergences in
      related protein families across plant clades.
AB  - Comparative genomic analyses are powerful tools that can be used to analyze the
      presence, conservation, and evolution of protein families and to elucidate issues
      concerning their function. To deal with these questions, we have chosen the clan
      CD of cysteine peptidases, which is formed by different protein families that
      play key roles in plants. An evolutionary comparative analysis of clan CD
      cysteine peptidases in representative species of different taxonomic groups that
      appeared during the evolution of the Viridiplantae was performed. The results
      obtained indicates: i) C13 GPI:protein transamidases, C14 metacaspases I, and C50
      separases are present in all taxonomic groups; ii) C13 legumains and C14
      metacaspases II are absent in some basal algae groups; iii) C11 clostripains have
      only been found in the two Chlorophyceae species; iv) C25 gingipains and C80 RTX
      toxins have not been found in plants. Moreover, gene duplication events could
      have been associated in some families to the increasing complexities acquired in
      land plants. These findings have demonstrated that comparative genomics is useful
      to provide valuable insights on the differential evolution of the related
      peptidase families belonging to clan CD in plant clades. The low number of
      protein members suggests a restricted physiological role for these peptidase
      families, mainly in algae species.

PMID- 19751812
TI  - Propranolol-magnesium aluminum silicate complex dispersions and particles:
      characterization and factors influencing drug release.
AB  - In this study, complexation of magnesium aluminum silicate (MAS) and propranolol
      HCl (PPN) in the form of dispersions and solid particles was investigated. PPN
      MAS dispersions at different pHs were prepared and characterized. The
      physicochemical properties and in vitro drug release of the complexes were also
      examined. Incorporation of PPN into MAS dispersions at various pHs caused the
      formation of PPN-MAS flocculates with a different particle size, zeta potential
      and amount of PPN adsorbed. The PPN-MAS complexes prepared at various pHs were
      formed via cation exchange, hydrogen bonding and water bridging mechanisms, which
      were revealed by FTIR and solid-state (29)Si NMR spectroscopy. This led to the
      intercalation of PPN molecules into the silicate layers of MAS. In vitro drug
      release studies demonstrated that the kinetic release of PPN can be described
      using the particle diffusion controlled mechanism, suggesting that drug release
      was controlled by diffusion of the drug in aqueous channels in the particle
      matrix of the complexes. The PPN-MAS complexes provided a sustained-release of
      PPN after an initial burst release in acidic medium and pH 6.8 phosphate buffer
      when compared with the physical mixture and pure PPN powder. This was due to a
      slow diffusion of drug that was intercalated in the inside of the particle
      matrix. The preparation pH of the complexes did not influence the release of PPN;
      the important factors affecting drug release were particle size, percentage of
      drug loaded in the complexes and the type of release medium. This finding
      suggests that the PPN-MAS complexes obtained in this study are strong candidates
      for use as drug carriers in oral modified-release dosage forms.

PMID- 19751813
TI  - The effect of total extract of Securigera securidaca L. seeds on serum lipid
      profiles, antioxidant status, and vascular function in hypercholesterolemic rats.
AB  - AIM OF THE STUDY: Seeds of Securigera securidaca are used for the treatment of
      disorders such as hyperlipidemia, diabetes, and epilepsy in Iranian folk
      medicine. The possible hypolipidemic and antioxidative effects of hydroalcoholic
      extract of S. securidaca seeds as well as the effect of the extract on vascular
      reactivity were investigated in hypercholesterolemic rats. MATERIALS AND METHODS:
      High-fat fed wistar rats received orally different doses of the extract for 20
      days. At the end of the experiment vein blood and liver were collected to measure
      the lipid profile, lipid peroxidation, and antioxidative enzyme activities. The
      thoracic aorta was excised and used for isolated vessel preparation and
      histological study. RESULTS: The extract produced significant reductions (p<0.05)
      in the level of low-density lipoprotein (LDL) and triglyceride with concomitant
      reduction in lipid deposition in the liver. The extract also suppressed markedly
      (p<0.001) the hypercholesterolemia-induced elevation of malondialdehyde levels
      both in serum and liver. In hypercholesterolemic rats the endothelium-dependent
      vasodilatation was improved significantly (p<0.05) by 100mg/kg/day of the
      extract. However, in histological study no atherosclerotic lesion was observed.
      CONCLUSION: These results suggest that S. securidaca seed in addition to decrease
      lipid levels and peroxidation, is able to improve vascular endothelium-dependent
      relaxation in hypercholesterolemia.

PMID- 19751814
TI  - Antispasmodic and bronchodilator activities of Artemisia vulgaris are mediated
      through dual blockade of muscarinic receptors and calcium influx.
AB  - AIM OF THE STUDY: The present study describes antispasmodic, antidiarrheal,
      bronchodilatory and tracheo-relaxant activities of Artemisia vulgaris to
      rationalize some of its traditional uses. MATERIALS AND METHODS: Crude extract of
      Artemisia vulgaris (Av.Cr) was studied in the isolated tissue preparations of
      rabbit jejunum and guinea-pig trachea, as well as in the in vivo castor oil
      induced diarrhea and bronchodilatory techniques. RESULTS: Av.Cr which tested
      positive for alkaloids, coumarins, flavonoids, saponins, sterols, tannins and
      terpenes caused concentration-dependent (0.03-10mg/mL) relaxation of jejunum
      spontaneous contractions. Av.Cr inhibited the carbachol (CCh, 1 microM) and K(+)
      (80 mM)-induced contractions in a pattern, similar to that of dicyclomine. Av.Cr
      shifted the Ca(2+) concentration-response curves to right, like that caused by
      verapamil and dicyclomine. Av.Cr produced rightward parallel shift in CCh-curves,
      followed by non-parallel shift at higher concentration with the suppression of
      the maximum response, similar to that caused by dicyclomine. It exhibited
      protective effect against castor oil-induced diarrhea and CCh-mediated
      bronchoconstriction in rodents. In trachea, Av.Cr relaxed the CCh (1 microM) and
      K(+) (80 mM)-induced contractions and shifted the CCh-curves to right.
      CONCLUSION: These results indicate that Artemisia vulgaris exhibits combination
      of anticholinergic and Ca(2+) antagonist mechanisms, which provides
      pharmacological basis for its folkloric use in the hyperactive gut and airways
      disorders, such as abdominal colic, diarrhea and asthma.

PMID- 19751815
TI  - NF-kappaB signaling as a putative target for omega-3 metabolites in the
      prevention of age-related macular degeneration (AMD).
AB  - Age-related macular degeneration (AMD) is the major reason of blindness of the
      elderly all over the world. AMD is characterized by a progressive loss of central
      vision attributable to degenerative and neovascular changes in the macula, the
      highly specialized region of the retina responsible for sharp and color visual
      acuity. Degeneration and cell death of retinal pigment epithelial cells (RPE)
      cause secondarily adverse effects on neural retina leading to visual loss. Most
      AMD patients cannot benefit from any treatment modalities. The prevalence of AMD
      is rising as a consequence of the aging of the population. As the RPE cells age,
      they are subject to continued oxidative stress and this believed to induce
      inflammation and progression of AMD. Interestingly, many clinical trials have
      revealed that dietary intakes of omega-3 fatty acids can reduce the risk of both
      early and late AMD, although their molecular targets in cellular signaling in AMD
      pathology are not understood. Recently, it has been proposed that the omega-3
      fatty acid metabolites, resolvins and protectins, function as endogenous anti
      inflammatory compounds. In this review, we propose that resolvins and protectins
      mediate their beneficial effects by preventing NF-kappaB signaling and this that
      may represent a new target for regulating the inflammatory responses in AMD.

PMID- 19751816
TI  - Fetal malformations and early embryonic gene expression response in cynomolgus
      monkeys maternally exposed to thalidomide.
AB  - The present study was performed to determine experimental conditions for
      thalidomide induction of fetal malformations and to understand the molecular
      mechanisms underlying thalidomide teratogenicity in cynomolgus monkeys.
      Cynomolgus monkeys were orally administered thalidomide at 15 or 20mg/kg-d on
      days 26-28 of gestation, and fetuses were examined on day 100-102 of gestation.
      Limb defects such as micromelia/amelia, paw/foot hyperflexion, polydactyly,
      syndactyly, and brachydactyly were observed in seven of eight fetuses. Cynomolgus
      monkeys were orally administered thalidomide at 20mg/kg on day 26 of gestation,
      and whole embryos were removed from the dams 6h after administration. Three
      embryos each were obtained from the thalidomide-treated and control groups. Total
      RNA was isolated from individual embryos, amplified to biotinylated cRNA and
      hybridized to a custom Non-Human Primate (NHP) GeneChip((R)) Array. Altered genes
      were clustered into genes that were up-regulated (1281 genes) and down-regulated
      (1081 genes) in thalidomide-exposed embryos. Functional annotation by Gene
      Ontology (GO) categories revealed up-regulation of actin cytoskeletal remodeling
      and insulin signaling, and down-regulation of pathways for vasculature
      development and the inflammatory response. These findings show that thalidomide
      exposure perturbs a general program of morphoregulatory processes in the monkey
      embryo. Bioinformatics analysis of the embryonic transcriptome following maternal
      thalidomide exposure has now identified many key pathways implicated in
      thalidomide embryopathy, and has also revealed some novel processes that can help
      unravel the mechanism of this important developmental phenotype.

PMID- 19751817
TI  - Microarray analysis of Leflunomide-induced limb malformations in CD-1 mice.
AB  - The immuno-suppressant Leflunomide, a potent inhibitor of dihydroorotate
      dehydrogenase (DHODH) and tyrosine kinases, is teratogenic in laboratory animals.
      To better understand its teratogenic mechanism, pregnant mice (CD-1) received a
      single dose of 70mg/kg Leflunomide, or vehicle control, by gastric intubation on
      gestation day 10. Gene expression was evaluated in the pooled fore- and hindlimb
      buds of embryos 4 and 24h post-treatment. The down-regulation of cholesterol
      biosynthesis-related genes was observed but could not be correlated with
      teratogenicity, since Leflunomide did not alter cholesterol concentration in limb
      bud. Leflunomide inhibited the mitosis of limb mesenchymal cells, which may be
      linked to DHODH inhibition as well as a potential effect on tyrosine kinases that
      mediate cytokine and growth factor signaling and that may be responsible for the
      Leflunomide's teratogenicity.

PMID- 19751818
TI  - Distribution of the cellular prion protein in the central nervous system of the
      chicken.
AB  - The cellular prion protein (PrP), a cell membrane-bound glycoprotein mainly
      located in the dendrites and axons of the central nervous system (CNS), is
      responsible for transmissible spongiform encephalopathies in mammals. PrP genes
      are widely conserved in vertebrates. In birds, the presence of PrP mRNA has been
      confirmed in neurons of the chicken brain, but localization of the protein
      remains to be determined. In the present study, we demonstrated the regional
      distribution of PrP in the CNS of adult chickens by immunohistochemical staining
      with a monoclonal antibody that recognizes chicken PrP 161-164. Immunoreactivity
      was observed in the neuropil, but not in neuronal somata or glial cells. It was
      preferentially intense in the olfactory bulb, the dorsal thalamus, the
      hypothalamus, and most regions of the telencephalon. Immunostaining became less
      intense toward the brainstem, but many nuclei were immunoreactive. Among
      brainstem nuclei, moderate immunostaining was observed in the nucleus of the
      solitary tract, dorsal motor nucleus of the vagus nerve, and substantia
      gelatinosa Rolandi. The cerebellar cortex was devoid of PrP immunoreactivity. The
      dorsal horn in the spinal cord was strongly immunoreactive. In situ hybridization
      with two probes of the C-terminal portion demonstrated localization of PrP mRNA
      in neurons of the brain and spinal cord. These findings suggest that PrP in the
      chicken CNS is localized in the dendrites and axons of neurons and that it is
      associated with certain sensory systems.

PMID- 19751819
TI  - Direct chemiluminescence detection of nitric oxide in aqueous solutions using the
      natural nitric oxide target soluble guanylyl cyclase.
AB  - Nitric oxide (NO) is a free radical involved in many physiological processes
      including regulation of blood pressure, immune response, and neurotransmission.
      However, the measurement of extremely low, in some cases subnanomolar,
      physiological concentrations of nitric oxide presents an analytical challenge.
      The purpose of this methods article is to introduce a new highly sensitive
      chemiluminescence approach to direct NO detection in aqueous solutions using a
      natural nitric oxide target, soluble guanylyl cyclase (sGC), which catalyzes the
      conversion of guanosine triphosphate to guanosine 3',5'-cyclic monophosphate and
      inorganic pyrophosphate. The suggested enzymatic assay uses the fact that the
      rate of the reaction increases by about 200 times when NO binds with sGC and, in
      so doing, provides a sensor for nitric oxide. Luminescence detection of the above
      reaction is accomplished by converting inorganic pyrophosphate into ATP with the
      help of ATP sulfurylase followed by light emission from the ATP-dependent
      luciferin-luciferase reaction. Detailed protocols for NO quantification in
      aqueous samples are provided. The examples of applications include measurement of
      NO generated by a nitric oxide donor (PAPA-NONOate), nitric oxide synthase, and
      NO gas dissolved in buffer. The method allows for the measurement of NO
      concentrations in the nanomolar range and NO generation rates as low as 100
      pM/min.

PMID- 19751820
TI  - Acquisition of doxorubicin resistance in ovarian carcinoma cells accompanies
      activation of the NRF2 pathway.
AB  - It has been firmly established that the transcription factor NRF2 is a critical
      element in the survival of healthy cells in response to oxidative stress because
      it up-regulates a wide array of antioxidant genes by binding to the antioxidant
      response element (ARE). However, adaptive activation of the NRF2 system after an
      exposure of cancer cells to chemotherapy can be hypothesized, implying the
      acquisition of chemoresistance by tumors. In this study we have investigated the
      potential role of NRF2 signaling in the development of acquired resistance to
      doxorubicin. The human ovarian carcinoma cell line A2780, which is highly
      sensitive to doxorubicin, showed low levels of ARE binding and ARE-driven
      luciferase activity, as well as repressed expression of its target genes compared
      with resistant ovarian carcinoma SKOV3 and OV90 cells. Doxorubicin-resistant
      A2780DR cells, established after exposure to stepwise increasing concentrations
      of doxorubicin, displayed a refractoriness to doxorubicin-induced cell death.
      Acquisition of doxorubicin resistance in A2780 cells was accompanied by an
      elevation in NRF2 activity and consequent increase in the expression of the
      catalytic subunit of gamma-glutamylcysteine ligase and total GSH content. A
      critical role for NRF2 in the acquired chemoresistance of A2780DR cells could be
      confirmed by the restoration of doxorubicin sensitivity after stable expression
      of NRF2-specific shRNA in A2780DR cells, whereas inhibition of NRF2 could not
      further enhance doxorubicin sensitivity in the parental A2780 cells. These
      results suggest that the level of NRF2 activity might be a determining factor for
      doxorubicin sensitivity in ovarian carcinoma cell lines and adaptive activation
      of the NRF2 system can participate in the development of acquired resistance to
      anthracycline therapy.

PMID- 19751822
TI  - Vitamin E and C supplementation does not ameliorate muscle dysfunction after
      anterior cruciate ligament surgery.
AB  - Muscle atrophy and weakness are predominant impairments after anterior cruciate
      ligament (ACL) surgical repair. We tested the hypothesis that vitamin E and C
      supplementation will improve recovery from ACL injury. Men undergoing elective
      ACL surgery were randomly assigned to twice-daily supplements of either
      antioxidants (AO; vitamins E and C, n=10) or matching placebos (n=10) from 2
      weeks before until 3 months after surgery. Each subject provided several fasting
      blood draws, two muscle biopsies from the thigh muscle of the injured limb, and
      strength and thigh circumference measurements of the lower limbs. Muscle atrophy
      was apparent in both groups before and several days after surgery. Compared with
      baseline measurements, peak isometric force of the injured limb increased
      significantly (P<0.05) by 3 months postsurgery in both treatment groups; however,
      AO supplementation did not augment these strength gains. By contrast, baseline
      plasma ascorbic acid concentrations correlated (r=0.59, P=0.006) with subsequent
      improvement in the strength of the injured limb. In summary, vitamin E and C
      supplementation was ineffective in potentiating the improvement in force
      production by the injured limb; however, baseline vitamin C status was associated
      with beneficial outcomes in strength, suggesting that long-term dietary habits
      are more effective than short-term supplements.

PMID- 19751823
TI  - Isolevuglandins covalently modify phosphatidylethanolamines in vivo: detection
      and quantitative analysis of hydroxylactam adducts.
AB  - Levuglandins (LGs) and isolevuglandins (isoLGs, also called "isoketals" or
      "isoKs") are extraordinarily reactive products of cyclooxygenase- and free
      radical-induced oxidation of arachidonates. We now report the detection in vivo
      and quantitative analysis of LG/isoLG adducts that incorporate the amino group of
      phosphatidylethanolamines (PEs) into LG/isoLG-hydroxylactams. Notably, LC-MS/MS
      detection of these hydroxylactams is achieved with samples that are an order of
      magnitude smaller and sample processing is much simpler and less time consuming
      than required for measuring protein-derived LG/isoLG-lysyl lactams. A key feature
      of our protocol is treatment of biological phospholipid extracts with
      phospholipase A(2) to generate mainly 1-palmitoyl-2-lysoPE-hydroxylactams from
      heterogeneous mixtures of phospholipids with a variety of acyl groups on the 2
      position. Over 160% higher mean levels of LG/isoLG-PE-hydroxylactam (P<0.001)
      were detected in liver from chronic ethanol-fed mice (32.4+/-6.3 ng/g, n=6)
      compared to controls (12.1+/-1.5 ng/g, n=4), and mean levels in plasma from
      patients with age-related macular degeneration (5.2+/-0.4 ng/ml, n=15) were
      elevated approximately 53% (P<0.0001) compared to those of healthy volunteers
      (3.4+/-0.1 ng/ml, n=15). Just as LG/isoLG-protein adducts provide a dosimeter of
      oxidative injury, this study suggests that LG/isoLG-PE-hydroxylactams are
      potential biomarkers for assessing risk for oxidative stress-stimulated diseases.

PMID- 19751824
TI  - ROS inhibit the expression of testicular steroidogenic enzyme genes via the
      suppression of Nur77 transactivation.
AB  - Steroidogenesis decreases with aging in the testis, whereas the levels of
      reactive oxygen species (ROS) increase. In addition, ROS have been reported to
      inhibit testicular steroidogenesis. Here, we investigated the effects of ROS on
      the transcriptional activity of Nur77, one of the major transcription factors
      that regulate the expression of steroidogenic enzyme genes. ROS signaling
      inhibited Nur77 transactivation, which was diminished by either treatment with c
      Jun N-terminal kinase (JNK) inhibitor or the expression of a dominant negative
      form of JNK. This suggests the involvement of JNK signaling, which elevates the
      expression of c-Jun as well as its phosphorylation in Leydig cells. In transient
      transfection assays, c-Jun suppressed Nur77 transactivation in a dose-dependent
      manner. Further studies using c-Jun mutants revealed that the protein level of c
      Jun, but not phosphorylation itself, was important for the suppression of Nur77
      transactivation. Nur77 directly interacted with c-Jun in vivo, which blocked the
      DNA binding activity of Nur77. Together, these results suggest that ROS signaling
      mediated c-Jun upregulation suppresses the expression of steroidogenic enzyme
      genes by inhibiting Nur77 transactivation, resulting in the reduction of
      testicular steroidogenesis. These findings may provide a mechanistic explanation
      for the age-related decline in testicular steroid hormone production.

PMID- 19751825
TI  - The effects of prenatal exposure to buprenorphine or methadone on infant visual
      evoked potentials.
AB  - This study compared the neurological development of 4 month old infants exposed
      to buprenorphine or methadone during pregnancy to that of a control group of non
      exposed infants. Participants were 30 buprenorphine-maintained women, 22
      methadone-maintained women and 33 non opioid-dependent controls, and their
      infants. Women were enrolled during pregnancy as part of an open-label non
      randomised flexible-dosing longitudinal study. Groups were matched for maternal
      age, parity, gravida, and tobacco and alcohol use. Infant neurological
      development was assessed by measuring latency of pattern reversal visual evoked
      potentials (VEP). One-way between groups analyses of variance (ANOVA) were
      conducted to test the statistical significance of differences between the mean
      latencies of the peak response to two different sized checkerboard patterns (48'
      and 69' of retinal arc). Infants prenatally exposed to methadone had
      significantly prolonged latencies, compared with infants in the control group and
      infants prenatally exposed to buprenorphine, in response to checks of 48' and
      69'. VEP latencies of infants prenatally exposed to buprenorphine did not differ
      significantly from controls for either check size. After adjustment for
      covariates, prenatal exposure to methadone remained a significant predictor of
      VEP response to checks of 48', but not 69'. Maternal self-reported used of
      marijuana during pregnancy made a significant unique contribution to the variance
      in P1 latencies for both check sizes. Data from this controlled, non-randomised
      study suggest that buprenorphine may confer an advantage over methadone as a
      maintenance drug during pregnancy in terms of infant neural development at 4
      months of age.

PMID- 19751826
TI  - From the primordial soup to the latest universal common ancestor.
AB  - This special issue of Research in Microbiology is dedicated to the origin of Life
      and of microbiology. One hundred and fifty years after Darwin's 'Origin of the
      Species', which is basically about the principles of natural selection, the
      origin of Life, which largely coincides with the origin of natural selection,
      remains the most enigmatic and fascinating problem in biology.

PMID- 19751827
TI  - Mitochondria, oxidative metabolism and cell death in stroke.
AB  - Stroke most commonly results from occlusion of a major artery in the brain and
      typically leads to the death of all cells within the affected tissue.
      Mitochondria are centrally involved in the development of this tissue injury due
      to modifications of their major role in supplying ATP and to changes in their
      properties that can contribute to the development of apoptotic and necrotic cell
      death. In animal models of stroke, the limited availability of glucose and oxygen
      directly impairs oxidative metabolism in severely ischemic regions of the
      affected tissue and leads to rapid changes in ATP and other energy-related
      metabolites. In the less-severely ischemic "penumbral" tissue, more moderate
      alterations develop in these metabolites, associated with near normal glucose use
      but impaired oxidative metabolism. This tissue remains potentially salvageable
      for at least the first few hours following stroke onset. Early restoration of
      blood flow can result in substantial recovery of energy-related metabolites
      throughout the affected tissue. However, glucose oxidation is markedly decreased
      due both to lower energy requirements in the post-ischemic tissue and limitations
      on the mitochondrial oxidation of pyruvate. A secondary deterioration of
      mitochondrial function subsequently develops that may contribute to progression
      to cell loss. Mitochondrial release of multiple apoptogenic proteins has been
      identified in ischemic and post-ischemic brain, mostly in neurons.
      Pharmacological interventions and genetic modifications in rodent models strongly
      implicate caspase-dependent and caspase-independent apoptosis and the
      mitochondrial permeability transition as important contributors to tissue damage,
      particularly when induced by short periods of temporary focal ischemia.

PMID- 19751829
TI  - Direct antioxidant and protective effect of estradiol on isolated mitochondria.
AB  - Estrogens have antioxidant properties which are due to their ability to bind to
      estrogen receptors and to up-regulate the expression of antioxidant enzymes via
      intracellular signalling pathways. Mitochondria are key organelles in the
      development of age-associated cellular damage. Recently, estrogen receptors were
      identified in mitochondria. The aim of this paper was to test whether estradiol
      directly affects mitochondria by preventing oxidative stress and protecting frail
      mitochondria. Incubation with estradiol at normal intracellular concentrations
      prevents the formation of reactive oxygen species by mitochondria in a saturable
      manner. Moreover, estradiol protects mitochondrial integrity as indicated by an
      increase in mitochondrial membrane potential. It also prevents the apoptogenic
      leakage of cytochrome c from mitochondria and as a result the mitochondrial
      content of this cytochrome c is maintained high. Thus, estradiol prevents the
      onset of the mitochondrial pathway of apoptosis by a direct effect on the
      organelle. Genistein, a phytoestrogen present at high concentration in soy,
      mimics the protective effect of estradiol by both decreasing the rate of
      formation of reactive oxygen species and preventing the release of cytochrome c
      from mitochondria.

PMID- 19751828
TI  - Mitochondrial and apoptotic neuronal death signaling pathways in cerebral
      ischemia.
AB  - Mitochondria play important roles as the powerhouse of the cell. After cerebral
      ischemia, mitochondria overproduce reactive oxygen species (ROS), which have been
      thoroughly studied with the use of superoxide dismutase transgenic or knockout
      animals. ROS directly damage lipids, proteins, and nucleic acids in the cell.
      Moreover, ROS activate various molecular signaling pathways. Apoptosis-related
      signals return to mitochondria, then mitochondria induce cell death through the
      release of pro-apoptotic proteins such as cytochrome c or apoptosis-inducing
      factor. Although the mechanisms of cell death after cerebral ischemia remain
      unclear, mitochondria obviously play a role by activating signaling pathways
      through ROS production and by regulating mitochondria-dependent apoptosis
      pathways.

PMID- 19751830
TI  - Multifaceted deaths orchestrated by mitochondria in neurones.
AB  - Neurones undergo diverse forms of cell death depending on the nature and severity
      of the stress. These death outcomes are now classified into various types of
      programmed cell death, including apoptosis, autophagy and necrosis. Each of these
      pathways can run in parallel and all have mitochondria as a central feature.
      Recruitment of mitochondria into cell death signalling involves either (or both)
      induction of specific death responses through release of apoptogenic proteins
      into the cytosol, or perturbation in function leading to loss of mitochondrial
      energization and ATP synthesis. Cross-talk between these signalling pathways,
      particularly downstream of mitochondria, determines the resultant pattern of cell
      death. The differential recruitment of specific death pathways depends on the
      timing of engagement of mitochondrial signalling. Other influences on programmed
      cell death pathways occur through stress of the endoplasmic reticulum and the
      associated ubiquitin-proteasome system normally handling potentially neurotoxic
      protein aggregates. Based upon contemporary evidence apoptosis is a relatively
      rare in the mature brain whereas the contribution of programmed necrosis to
      various neuropathologies has been underestimated. The death outcomes that
      neurones exhibit during acute or chronic injury or pathological conditions
      considered here (oxidative stress, hypoxic-ischaemic injury, amyotrophic lateral
      sclerosis, Parkinson's and Huntington's diseases) fall within a spectrum of the
      diverse death types across the apoptosis-necrosis continuum. Indeed, dying or
      dead neurones may simultaneously manifest characteristics of more than one type
      of death pathway. Understanding neuronal death pathways and their cross-talk not
      only informs the detailed pathobiology but also suggests novel therapeutic
      strategies.

PMID- 19751821
TI  - Oxidative risk for atherothrombotic cardiovascular disease.
AB  - In the vasculature, reactive oxidant species, including reactive oxygen,
      nitrogen, or halogenating species, and thiyl, tyrosyl, or protein radicals may
      oxidatively modify lipids and proteins with deleterious consequences for vascular
      function. These biologically active free radical and nonradical species may be
      produced by increased activation of oxidant-generating sources and/or decreased
      cellular antioxidant capacity. Once formed, these species may engage in reactions
      to yield more potent oxidants that promote transition of the homeostatic vascular
      phenotype to a pathobiological state that is permissive for atherothrombogenesis.
      This dysfunctional vasculature is characterized by lipid peroxidation and
      aberrant lipid deposition, inflammation, immune cell activation, platelet
      activation, thrombus formation, and disturbed hemodynamic flow. Each of these
      pathobiological states is associated with an increase in the vascular burden of
      free radical species-derived oxidation products and, thereby, implicates
      increased oxidant stress in the pathogenesis of atherothrombotic vascular
      disease.

PMID- 19751831
TI  - Animal models reveal role for tau phosphorylation in human disease.
AB  - Many proteins that are implicated in human disease are posttranslationally
      modified. This includes the microtubule-associated protein tau that is deposited
      in a hyperphosphorylated form in brains of Alzheimer's disease patients. The
      focus of this review article is on the physiological and pathological
      phosphorylation of tau; the relevance of aberrant phosphorylation for disease;
      the role of kinases and phosphatases in this process; its modeling in transgenic
      mice, flies, and worms; and implications of phosphorylation for therapeutic
      intervention.

PMID- 19751832
TI  - Heat shock proteins protect platyfish (Xiphophorus maculatus) from Yersinia
      ruckeri induced mortality.
AB  - The significant disadvantages accompanied with the use of antibiotics in
      aquaculture, emphasize the need for developing alternative disease control
      strategies, like novel vaccine approaches and immunostimulating measures. Several
      studies have already pointed out the ability of heat shock proteins (HSPs) to
      modulate innate and adaptive immune responses, what makes them potent candidates
      for the development of a new disease prevention method. In this study, the use of
      self and non-self heat shock proteins as a new prophylactic treatment against
      bacterial diseases in freshwater aquaculture was investigated. Therefore, an
      infection model was developed with platyfish as a host for Yersinia ruckeri
      infections. In this infection model, the effect of different treatments with HSPs
      on the survival of the fish after bacterial infection was tested: non-lethal heat
      shock, intracoelomal injection with two recombinant bacterial HSPs, GroEL and
      DnaK, and a combination of a non-lethal heat shock and an injection with
      bacterial HSPs. The results show that a non-lethal heat shock could not protect
      fish against a subsequent infection with Y. ruckeri. However, when the fish
      received an injection with bacterial HSPs, Y. ruckeri induced mortality was
      reduced. This effect became significant when the administration of bacterial HSPs
      was combined with a non-lethal heat shock. These data suggest a possible role for
      heat shock proteins as an immunostimulating treatment in fish against bacterial
      infections.

PMID- 19751834
TI  - Molecular cloning of mud crab Scylla serrata peroxinectin and its expression
      following Vibrio alginolyticus and peptidoglycan injections.

PMID- 19751835
TI  - Mutations in the Aeromonas salmonicida subsp. salmonicida type III secretion
      system affect Atlantic salmon leucocyte activation and downstream immune
      responses.
AB  - Deletion mutants of Aeromonas salmonicida subsp. salmonicida were used to
      determine the effect of the type three secretion system (TTSS) on Atlantic salmon
      anterior head kidney leucocytes (AHKL). One strain had a deletion in the outer
      membrane pore gene, ascC; and the other in three effector genes: aopO, aopH and
      aexT (we call this strain Deltaaop3). Host cell invasion success and 24h survival
      were depressed in DeltaascC, as was 24h survival of Deltaaop3, when compared to
      the wild type strain. Challenge of AHKLs with A449 or TTSS mutants stimulated
      expression of the inflammatory mediators IL-8, IL-1 and TNFalpha at two bacterial
      concentrations (A(600) 0.1, 0.01). Expression of IL-12 was not stimulated in
      DeltaascC challenged cells, whereas A449 and Deltaaop3 challenge resulted in an
      up-regulation of IL-12 in AHKLs, 2- and 4-fold higher than PBS, respectively.
      Only the wild type strain elicited a significant increase in IL-10 expression
      (5.5x at A(600) 0.1). Inducible nitric oxide synthetase (iNOS) and arginase
      (I+II) genes were also significantly up-regulated upon exposure to all strains.
      However, iNOS:arginase ratio was elevated in the effector mutant challenge. These
      results suggest that A. salmonicida subsp. salmonicida may enhance survival
      within the host cell through polarization of macrophages/leucocytes to an
      alternative, rather than classical, activation state. Furthermore, the short-term
      survival and lack of T-cell signalling cytokine stimulation in DeltaascC, may
      help explain its inefficiency at providing protection to subsequent wild type
      challenge.

PMID- 19751833
TI  - Identification of immune related genes in Atlantic halibut (Hippoglossus
      hippoglossus L.) following in vivo antigenic and in vitro mitogenic stimulation.
AB  - To identify and characterize genes and proteins of the Atlantic halibut
      (Hippoglossus hippoglossus) immune system, six cDNA libraries were constructed
      from liver, kidney, spleen, peripheral blood, and thymus. Halibut were injected
      with nodavirus, infectious pancreatic necrosis virus (IPNV), or vibriosis vaccine
      and tissue samples were collected at various time points. Leukocytes from
      peripheral blood and spleen from stimulated and mock-injected fish were isolated
      and further in vitro activated with the mitogens, concanavalin A (Con A) and
      phorbol myristate acetate (PMA) to facilitate activation and proliferation. A
      total of 5117 high quality expressed sequence tags (ESTs) were identified and
      assembled into 781 contigs and 2796 singletons. Amongst these ESTs, 147 different
      putative immune related genes were identified. Several genes involved in innate
      and adaptive immune responses such as complement proteins, immunoglobulins, cell
      surface receptors, and cytokines and chemokines were identified. Of the immune
      related genes identified in this study, 44% had no match against any of the
      publicly available sequence data for halibut and thus can be considered as novel
      identification in halibut species. The approach of combining in vivo antigenic
      with in vitro mitogen stimulation, in addition to preparation of cDNA libraries
      from thymus enabled identification of many of the interesting genes including
      those involved in T-cell receptor complex.

PMID- 19751836
TI  - Transthyretin gene (TTR) intron 1 elucidates crocodylian phylogenetic
      relationships.
AB  - Transthyretin (TTR) is an attractive candidate for use in phylogenetic analysis
      because it is a short, single-copy nuclear gene with regions that are highly
      conserved across evolutionarily-divergent organisms from Xenopus laevis to Homo
      sapiens. To explore its utility as a phylogenetic marker, the complete intron one
      region (789-805 bp) was sequenced in 22 crocodylian species. Detailed analyses of
      intron 1 resolved the three expected lineages, Alligatorids, Crocodylids, and
      Gavialids, and offered additional evidence for the utility of synapomorphic
      indels in elucidating higher-level phylogenetic relationships. When used in
      conjunction with other genetic and morphological data sets, intron 1 should be a
      valuable tool in the investigation of other closely related taxa.

PMID- 19751837
TI  - Patterns of diversification and ancestral range reconstruction in the southeast
      Asian-Pacific angiosperm lineage Cyrtandra (Gesneriaceae).
AB  - The genus Cyrtandra is the largest in the Gesneriaceae family and is one of the
      most widely dispersed plant genera in southeast Asia and the Pacific. Species of
      Cyrtandra are morphologically diverse but characters are often homoplastic
      causing considerable difficulty in defining monophyletic classification units. In
      this study, we used molecular phylogenetic analysis of 88 taxa representing
      approximately 70 species to construct a well-resolved evolutionary hypothesis for
      Cyrtandra. Diversification rates analysis and ancestral range analysis were also
      conducted to infer timing of major lineage divergences and geographic origin of
      these lineages, principally among Pacific species. Using these data, we compared
      existing classification schemes to better understand the applicability of current
      taxonomy. Divergence time estimates support a diversification of the Pacific
      clade at approximately 20 MYBP. Although the origin of the Pacific lineage
      remains unresolved, ancestral range reconstruction analysis supports Fiji as the
      most likely "first-step" into the Pacific with subsequent dispersals to Hawai'i,
      and other archipelagos. A greater Fiji-Samoa region, corresponding with
      Takhtajan's Fijian Region, is implicated as a major Pacific region interface and
      possibly a center of origin for expansion of Cyrtandra throughout the Pacific.
      Among South Pacific taxa sampled, several supported clades in our evolutionary
      hypothesis are characterized by distinct morphological traits possibly warranting
      sectional rankings. Relationships among Hawaiian taxa are less resolved and the
      distributions of species within this clade do not consistently correspond to
      existing sectional rankings. More detailed, population-level research is needed
      to clarify these relationships. We argue that future sectional classifications
      should correspond with monophyletic lineages and that species-level relationships
      should be more closely studied within these lineages.

PMID- 19751838
TI  - Molecular phylogeny, divergence time estimates, and historical biogeography of
      Circaea (Onagraceae) in the Northern Hemisphere.
AB  - Circaea (Onagraceae) consists of eight species and six subspecies distributed in
      Eurasia and North America. The sister group of Circaea was recently shown to be
      Fuchsia, which comprises 107 species primarily distributed in montane Central and
      South America, including four species occurring in the South Pacific islands.
      Three plastid markers (petB-petD, rpl16, and trnL-F) and nrITS sequences from 13
      of the 14 taxa of Circaea were sequenced and used to reconstruct the phylogenetic
      and biogeographic history of the genus. Parsimony and Bayesian analyses support
      that (1) Circaea is monophyletic; (2) the bilocular group is a weakly supported
      clade nested within the unilocular grade; (3) neither the C. alpina complex nor
      the C. canadensis complex is monophyletic; and (4) the western North American C.
      alpina subsp. pacifica diverged first in the genus. Divergence time estimates
      based on the Bayesian "relaxed" clock methods suggest that the earliest Circaea
      divergence occurred minimally at 16.17 mya (95% HPD: 7.69-24.53 mya).
      Biogeographic analyses using divergence-vicariance analysis (DIVA) and a
      likelihood method support the New World origin of Circaea. Three independent
      dispersal events between Eurasia and North America via the Bering land bridge
      were inferred within Circaea. Higher taxon diversity of Circaea in eastern Asia
      was probably caused by geologic and ecological changes during the late Tertiary
      in the Northern Hemisphere.

PMID- 19751839
TI  - Phylogenetic relationships of phrynosomatid lizards based on nuclear and
      mitochondrial data, and a revised phylogeny for Sceloporus.
AB  - Phrynosomatid lizards are among the most common and diverse groups of reptiles in
      western North America, Mexico, and Central America. Phrynosomatidae includes 136
      species in 10 genera. Phrynosomatids are used as model systems in many research
      programs in evolution and ecology, and much of this research has been undertaken
      in a comparative phylogenetic framework. However, relationships among many
      phrynosomatid genera are poorly supported and in conflict between recent studies.
      Further, previous studies based on mitochondrial DNA sequences suggested that the
      most species-rich genus (Sceloporus) is possibly paraphyletic with respect to as
      many as four other genera (Petrosaurus, Sator, Urosaurus, and Uta). Here, we
      collect new sequence data from five nuclear genes and combine them with published
      data from one additional nuclear gene and five mitochondrial gene regions. We
      compare trees from nuclear and mitochondrial data from 37 phrynosomatid taxa,
      including a "species tree" (from BEST) for the nuclear data. We also present a
      phylogeny for 122 phrynosomatid species based on maximum likelihood analysis of
      the combined data, which provides a strongly-supported hypothesis for
      relationships among most phrynosomatid genera and includes most phrynosomatid
      species. Our results strongly support the monophyly of Sceloporus (including
      Sator) and many of the relationships within it. We present a new classification
      for phrynosomatid lizards and the genus Sceloporus, and offer a new tree with
      branch lengths for use in comparative studies.

PMID- 19751840
TI  - Species trees for spiny lizards (genus Sceloporus): identifying points of
      concordance and conflict between nuclear and mitochondrial data.
AB  - Spiny lizards (genus Sceloporus) represent one of the most diverse and species
      rich clades of squamate reptiles in continental North America. Sceloporus
      contains 90+ species, which are partitioned into 21 species groups containing
      anywhere from one to 15 species. Despite substantial progress towards elucidating
      the phylogeographic patterns for many species of Sceloporus, efforts to resolve
      the phylogenetic relationships among the major species groups remain limited. In
      this study, the phylogenetic relationships of 53 species of Sceloporus,
      representing all 21 species groups, are estimated based on four nuclear genes
      (BDNF, PNN, R35, RAG-1; >3.3 kb) and contrasted with a new mitochondrial DNA
      genealogy based on six genes (12S, ND1, ND4, and the histidine, serine, and
      leucine tRNA genes; >2.5 kb). Species trees estimated from the nuclear loci using
      data concatenation or a coalescent-based inference method result in concordant
      topologies, but the coalescent approach provides lower resolution and support.
      When comparing nuclear versus mtDNA-based topologies for Sceloporus species
      groups, conflicting relationships outnumber concordant relationships.
      Incongruence is not restricted to weak or unresolved nodes as might be expected
      under a scenario of rapid diversification, but extends to conflicts involving
      strongly support clades. The points of concordance and conflict between the
      nuclear and mtDNA data are discussed, and arguments for preferring the species
      trees estimated from the multilocus nuclear data are presented.

PMID- 19751841
TI  - Evidence of three parallel evolutions of leaf dwarfism and phytogeography in
      Lysimachia sect. Nummularia in Japan and Taiwan.
AB  - Phylogenetic analyses were performed using nrITS variations of eight species
      including one variety of the genus Lysimachia sect. Nummularia in Japan and
      Taiwan, with another 34 Lysimachia species and Glaux maritime obtained from a DNA
      database. Among the four dwarf-leaf taxa in Japan and Taiwan, L. japonica var.
      minutissima of Japan and two Taiwanese species were placed into two different
      clades; and L. liukiuensis of Japan, was positioned outside of these two clades.
      These results suggest that three independent dwarfism events generated the four
      dwarf-leaf taxa; and that there were likely multiple migration events from China
      to Japan and Taiwan.

PMID- 19751842
TI  - Bioimaging has been a cornerstone of cell biology and developmental biology
      research.

PMID- 19751843
TI  - Blockade of neutrophil responses in aspiration pneumonia via ELR-CXC chemokine
      antagonism does not predispose to airway bacterial outgrowth.
AB  - Pneumonia associated with aspiration of bacterial-laden gastric contents is
      characterized by Glu-Leu-Arg (ELR)-CXC chemokine (e.g., CXC2L1, CXCL8) expression
      leading to local neutrophil sequestration. This neutrophil response is designed
      to be protective, but overly aggressive responses can be pathogenic in
      themselves. Herein we assessed whether blocking neutrophil responses in a guinea
      pig model of aspiration pneumonia would foster airway bacterial growth. Guinea
      pigs (n=5) were challenged intranasally with saline, acidified saline or
      acidified gastric contents (35mg/kg body weight, pH 2.0) and treated
      subcutaneously with 250mug/kg of the human ELR-CXC chemokine antagonist CXCL8((3
      72))K11R/G31P (G31P) or saline. After 20h the animals' airway inflammatory
      responses and bacterial burdens were assessed. A loss of vascular integrity was
      apparent in the lungs of the saline-treated aspiration pneumonia animals (12.07+/
      1.3% of the pleural surfaces exhibited hemorrhagic consolidation, 4.6x10(6)
      RBC/ml bronchoalveolar lavage fluid [BALF]), as was a pulmonary neutrophilia. The
      BAL fluids contained gram-negative and -positive bacteria (total load, 6.3+/
      3.2x10(7) CFU/ml BALF) that are associated with nosocomial infections in humans.
      The G31P-treatments attenuated the pulmonary vascular complications (2.27+/-0.5%
      pleural surface hemorrhagic consolidation, 0.46x10(6) RBC/ml BALF), and reduced
      the pulmonary neutrophilia by >/=86%. The G31P-treatments did not lead to
      significant changes in the airway bacterial loads (total load, 3.46+/-1.8x10(7)
      CFU/ml BALF). This data indicates that attenuation of the pulmonary neutrophil
      response in aspiration pneumonia reduces pathology very significantly but does
      not reduce the efficiency of pulmonary bacterial clearance.

PMID- 19751844
TI  - Immunolocalization of Na+/K+-ATPase and Na+/K+/2Cl- cotransporter in the tubular
      epithelia of sea snake salt glands.
AB  - The sublingual salt gland is the primary site of salt excretion in sea snakes;
      however, little is known about the mechanisms mediating ion excretion. Na(+)/K(+)
      ATPase (NKA) and Na(+)/K(+)/2Cl(-) cotransporter (NKCC) are two proteins known to
      regulate membrane potential and drive salt secretion in most vertebrate secretory
      cells. We hypothesized that NKA and NKCC would localize to the basolateral
      membranes of the principal cells comprising the tubular epithelia of sea snake
      salt glands. Although there is evidence of NKA activity in salt glands from
      several species of sea snake, the localization of NKA and NKCC and other
      potential ion transporters remains unstudied. Using histology and
      immunohistochemistry, we localized NKA and NKCC in salt glands from three species
      of laticaudine sea snake: Laticauda semifasciata, L. laticaudata, and L.
      colubrina. Antibody specificity was confirmed using Western blots. The compound
      tubular glands of all three species were found to be composed of serous secretory
      epithelia, and NKA and NKCC were abundant in the basolateral membranes. These
      results are consistent with the morphology of secretory epithelia found in the
      rectal salt glands of marine elasmobranchs, the nasal glands of marine birds and
      the gills of teleost fishes, suggesting a similar function in regulating ion
      secretion.

PMID- 19751845
TI  - Impact of the circadian clock on in vitro genotoxic risk assessment assays.
AB  - Our society expects safety assessment for drugs, chemicals, cosmetics, and foods,
      which to date cannot be achieved without the use of laboratory animals. At the
      same time, society aims at refining, reducing, and (ultimately) replacing animal
      testing. As a consequence, much effort is taken to establish alternatives, such
      as toxicogenomics-based risk assessment assays on cultured cells and tissues.
      Evidently, the properties of cells in vitro will considerably differ from the in
      vivo situation. This review will discuss the impact of the circadian clock, an
      internal time keeping system that drives 24-h rhythms in metabolism, physiology
      and behavior, on in vitro genotoxic risk assessment. Our recent observation that
      DNA damaging agents can synchronize the circadian clock of individual cells in
      culture (and as a consequence the cyclic expression of clock-controlled genes,
      comprising up to 10% of the transcriptome) implies that the circadian clock
      should not be neglected when developing cell or tissue-based alternatives for
      chronic rodent toxicity assays.

PMID- 19751846
TI  - Isolation and functional characterization of eIF4F components and poly(A)-binding
      protein from Plasmodium falciparum.
AB  - The multisubunit translation initiation complex eIF4F contains eIF4E, eIF4A and
      eIF4G. eIF4A is an ATP-dependent RNA helicase. eIF4G provides the platform for
      binding initiation factors and it contains the binding sites for eIF4A and eIF4E
      and interacts with poly(A)-binding protein (PABP). Although the genome of
      Plasmodium falciparum is fully sequenced but the gene annotation is still
      incomplete. In this manuscript we present the isolation and characterization of
      components of the eIF4F complex i.e. eIF4E, eIF4G and PABP from P. falciparum.
      Our studies indicate that PfeIF4E is involved in translation and PfPABP binds
      poly(A) specifically. We demonstrate the interaction of PfeIF4G with PfeIF4E,
      PfeIF4A (PfH45) and PfPABP. These studies demonstrate that these factors are
      structurally and functionally conserved. These studies will contribute to
      understand the important process and components of translation complex in the
      malaria parasite.

PMID- 19751847
TI  - C-type lectins from the nematode parasites Heligmosomoides polygyrus and
      Nippostrongylus brasiliensis.
AB  - The C-type lectin superfamily is highly represented in all metazoan phyla so far
      studied. Many members of this superfamily are important in innate immune defences
      against infection, while others serve key developmental and structural roles.
      Within the superfamily, many proteins contain multiple canonical carbohydrate
      recognition domains (CRDs), together with additional non-lectin domains. In this
      report, we have studied two gastrointestinal nematode parasites which are widely
      used in experimental rodent systems, Heligmosomoides polygyrus and
      Nippostrongylus brasiliensis. From cDNA libraries, we have isolated 3 new C-type
      lectins from these species; all are single-CRD proteins with short additional N
      terminal domains. The predicted Hp-CTL-1 protein contains 156 aa, Nb-CTL-1 191 aa
      and Nb-CTL-2 183 aa; all encode predicted signal peptides, as well as key
      conserved sequence motifs characteristic of the CTL superfamily. These lectins
      are most similar to C. elegans CLEC-48, 49 and 50, as well as to the lectin
      domains of mammalian immune system proteins CD23 and CD206. RT-PCR showed that
      these H. polygyrus and N. brasiliensis genes are primarily expressed in the gut
      dwelling adult stages, although Nb-CTL-2 transcripts are also prominent in the
      free-living infective larval (L3) stage. Polyclonal antibodies raised to Hp-CTL-1
      and Nb-CTL-1 reacted to both proteins by ELISA, and in Western blot analysis
      recognised a 15-kDa band in secreted proteins of adult N. brasiliensis (NES) and
      a 19-kDa band in H. polygyrus ES (HES). Anti-CTL-1 antibody also bound strongly
      to the cuticle of adult H. polygyrus. Hence, live parasites release C-type
      lectins homologous to some key receptors of the mammalian host immune system,
      raising the possibility that these products interfere in some manner with
      immunological recognition or effector function.

PMID- 19751848
TI  - Membrane-disruptive properties of the bioinsecticide Jaburetox-2Ec: implications
      to the mechanism of the action of insecticidal peptides derived from ureases.
AB  - Jaburetox-2Ec, a recombinant peptide derived from an urease isoform (JBURE-II),
      displays high insecticidal activity against important pests such as Spodoptera
      frugiperda and Dysdercus peruvianus. Although the molecular mechanism of action
      of ureases-derived peptides remains unclear, previous ab initio data suggest the
      presence of structural motifs in Jaburetox-2Ec with characteristics similar to
      those found in a class of pore-forming peptides. Here, we investigated the
      molecular aspects of the interaction between Jaburetox-2Ec and large unilamellar
      vesicles. Jaburetox-2Ec displays membrane-disruptive ability on acidic lipid
      bilayers and this effect is greatly influenced by peptide aggregation.
      Corroborating with this finding, molecular modeling studies revealed that
      Jaburetox-2Ec might adopt a well-defined beta-hairpin conformation similar to
      those found in antimicrobial peptides with membrane disruption properties. In
      addition, molecular dynamics simulations suggest that the protein is able to
      anchor at a polar/non-polar interface. In the light of these findings, for the
      first time it was possible to point out some evidence that the peptide Jaburetox
      2Ec interacting with lipid vesicles promotes membrane permeabilization.

PMID- 19751849
TI  - Sodium citrate as an effective dispersant for the synthesis of inorganic-organic
      composites with a nanodispersed mineral phase.
AB  - Although extensive efforts have been devoted to the development of polymer
      ceramic composites for bone repair, those developed thus far were not able to
      mimic the nanostructure of bone, partly because of the aggregated, microscale
      organization of the mineral component. As a consequence, homogenization and
      intermixing of organic and inorganic components remain a major engineering
      challenge for the development of functional, biomimetic bone-substituting
      composites. In the current study, various dispersants were evaluated for their
      potential to be used as biocompatible dispersants in the synthesis of biomimetic
      composites with a nanodispersed mineral phase. Based on sedimentation
      experiments, tribasic sodium citrate was selected as the most effective
      dispersant for the stabilization of calcium phosphate (CaP) suspensions. Specific
      adsorption of citrate anions onto CaP nanocrystals was shown to result in a
      strong increase in the negative surface charge of the CaP particles and
      consequently increased repulsive interparticle forces that were able to overcome
      attractive van der Waals forces. Using sodium citrate as dispersant at a
      CaP/citrate ratio of 4.0, CaP-gelatin nanocomposites were fabricated which
      displayed a nanostructured mineral phase without occurrence of microscale CaP
      particles. Consequently, aggregation and sedimentation of CaP mineral phase was
      reduced considerably.

PMID- 19751850
TI  - Biotinylation of silicon-doped hydroxyapatite: a new approach to protein fixation
      for bone tissue regeneration.
AB  - Silicon-doped hydroxyapatite has been functionalized with biotin molecules as a
      new methodology for the attachment of proteins, peptides or growth factors
      through the formation of avidin-biotin complex in this material. Bioceramic
      biotinylation has been performed by esterification reaction between the OH groups
      of hydroxyapatite and COOH groups of biotin molecules. Several parameters of the
      biotinylation, such as the addition of N,N'-dicyclohexylcarbodiimide (DCC), the
      biotin/bioceramic molar ratio and the activation time, have been studied in order
      to improve both the amount of anchored biotin on the bioceramic surface and its
      bond strength. The grafting of biotin on a silicon-doped hydroxyapatite surface
      was determined using (13)C nuclear magnetic resonance, Fourier transform infrared
      spectroscopy and elemental analyses. The results show that the addition of DCC
      significantly increases both the amount of biotin grafted and the bond strength,
      because the major part is through covalent bonding. Lixiviation studies in
      simulated body fluid (SBF) at 37 degrees C have confirmed such results, showing
      that the retention grade after 7 days in SBF was of ca. 63%. Fluorescein
      isothiocyanate-avidin complexation has been performed on three-dimensional (3-D)
      scaffolds prepared by a rapid-prototyping technique. Confocal microscopy studies
      show a homogeneous distribution with a higher incorporation rate of the protein
      over the entire external surface of the biotinylated 3-D scaffold.

PMID- 19751851
TI  - In vivo investigation of the inflammatory response against allylamine plasma
      polymer coated titanium implants in a rat model.
AB  - Titanium (Ti) is an established biomaterial for bone replacement. However,
      facilitation of osteoblast attachment by surface modification with chemical
      groups could improve the implant performance. Therefore, this study aimed to
      evaluate the effect of a plasma polymerized allylamine (PPAAm) layer on the local
      inflammation in a rat model. Three series (RM76AB, RM78AB, RM77AB) of PPAAm
      treated Ti plates were prepared using different plasma conditions. Twelve male
      LEW.1A rats received one plate of each series and one uncoated control plate
      implanted into the back musculature. After 7, 14 and 56 days, four rats were
      euthanized to remove the implants with surrounding tissue. Total
      monocytes/macrophages, tissue macrophages, T-cells and MHC-class-II-positive
      cells were morphometrically counted. On day 14, the macrophage/monocyte number
      was significantly higher for the controls than for the PPAAm samples. On day 56,
      the RM76AB and RM78AB samples had significantly lower numbers than RM77AB and the
      controls. The same was found for the tissue macrophages. No change over time and
      no differences between the implants were found for the T-cells. For the number of
      MHC-class-II-positive cells, a significant decrease was found only for the RM78AB
      implants between day 14 and day 56. Physico-chemical analysis of the PPAAm
      implants revealed that the RM77AB implants had the lowest water absorption, the
      highest nitrogen loss and the lowest oxygen uptake after sonication. These
      results demonstrate that the PPAAm samples and the controls were comparable
      regarding local inflammation, and that different plasma conditions lead to
      variations in the material properties which influence the tissue reaction.

PMID- 19751852
TI  - Ultrasound-guided catheterization of the internal jugular vein in oncologic
      patients; comparison with the classical anatomic landmark technique: a
      prospective study.
AB  - AIM: To compare the traditional anatomic landmark technique with the ultrasound
      guided method for central venous catheterization. MATERIAL AND METHODS: During
      three years, 551 patients underwent internal jugular vein catheterization; in 347
      patients, the ultrasound-guided technique was used, while in the other 204
      patients the catheter was introduced by using the classical anatomic landmark
      method. Operating time, complications (pneumothorax, puncture of carotid artery
      with or without hematoma formation), and number of attempts to achieve central
      venous catheterization were recorded. RESULTS: The ultrasound-guided technique
      was associated with significantly shorter operating time (9.83+/-3.1 vs. 20+/-4.4
      min, p<0.001) and less morbidity (pneumothorax, 0 vs. 2 patients [p<0.05],
      carotid artery puncture with or without hematoma formation, 1 vs. 16 patients
      [p<0.05]). Moreover, the ultrasound-guided technique was highly successful in
      achieving central venous catheterization (failure, 0 vs. 18 patients [p<0.05]),
      with significantly fewer attempts (1-3 attempts in 204 vs. 283 [p<0.01]),
      compared to the classical anatomic landmark technique. CONCLUSION: The ultrasound
      guided method is faster, more efficient, and less morbid procedure compared with
      the classical anatomic landmark technique. Therefore, it should be preferred over
      the classical landmark method, especially in high-risk patients for the
      development of complications.

PMID- 19751853
TI  - Keeping evidence-based recommendations up to date: the World Health
      Organization's global guidance for family planning.

PMID- 19751854
TI  - WHO provider brief on hormonal contraception and liver disease.

PMID- 19751855
TI  - Intrauterine device insertion during the postpartum period: a systematic review.
AB  - BACKGROUND: Insertion of an intrauterine device (IUD) at different times or by
      different routes during the postpartum period may increase the risk of
      complications. METHODS: We searched Medline, Lilacs and Cochrane Collaboration
      databases for articles in any language, between database inception until December
      2008, which compared outcomes of postpartum IUD insertion time intervals. Search
      terms included postpartum, puerperium, postcesarean delivery, cesarean section,
      IUD(s), IUCD(s), intrauterine device(s) and insertion. RESULTS: From 297
      articles, we identified 15 for inclusion in this review: all studies examined the
      outcomes from copper IUD insertions within the postpartum time period compared to
      other time intervals or compared routes (vaginal or via hysterotomy) of
      postpartum insertion. No studies of levonorgestrel IUDs were identified.
      Immediate IUD insertion (within 10 min of placental delivery) was safe when
      compared with later postpartum time periods and interval insertion. Immediate
      postpartum IUD insertion demonstrated lower expulsion rates when compared with
      delayed postpartum insertion but with higher rates than interval insertion.
      Immediate insertion following cesarean delivery demonstrated lower expulsion
      rates than immediate insertion following vaginal delivery. CONCLUSION: Poor to
      fair quality evidence from 15 articles demonstrated no increase in risk of
      complications among women who had an IUD inserted during the postpartum period;
      however, some increase in expulsion rates occurred with delayed postpartum
      insertion when compared to immediate insertion and with immediate insertion when
      compared to interval insertion. Postplacental placements during cesarean delivery
      are associated with lower expulsion rates than postplacental vaginal insertions,
      without increasing rates of postoperative complications.

PMID- 19751856
TI  - Use of contraceptive methods by women with current venous thrombosis on
      anticoagulant therapy: a systematic review.
AB  - BACKGROUND: As nearly all women with venous thromboembolism (VTE) will be treated
      with anticoagulant therapy, it is important to consider how anticoagulation
      affects the safety of contraceptive use. STUDY DESIGN: We conducted a systematic
      review of the literature regarding use of contraceptive methods in women with
      current VTE on anticoagulant therapy. Due to the limited direct evidence that was
      identified, we expanded our search to include women on anticoagulant therapy for
      indications other than VTE and women with bleeding disorders. RESULTS: Six
      articles met our inclusion criteria. Three observational studies found the
      levonorgestrel-releasing IUD (LNG-IUD) was an effective treatment for menorrhagia
      for women on anticoagulation therapy or with bleeding disorders. Prevention of
      recurrent hemorrhagic ovarian cysts was seen in women on chronic anticoagulation
      treated with depot-medroxyprogesterone acetate (DMPA) in one small observational
      study. Among women with bleeding disorders, no complications were seen in 16
      women with placement of the LNG-IUD. One pharmacokinetic study found no
      statistically significant interaction between combined oral contraceptives and
      warfarin. Other than one case report, no evidence was found regarding the risk of
      recurrent thrombosis in women on anticoagulation therapy using a contraceptive
      method. CONCLUSION: The majority of studies in this review examined treatment
      effects of the LNG-IUD or DMPA on complications of anticoagulation and found
      overall beneficial effects of their use in these circumstances. Minimal evidence
      in women with inherited bleeding disorders suggests that insertion of the LNG-IUD
      does not pose major bleeding risks in these women with appropriate management.

PMID- 19751857
TI  - Progestogen-only contraceptive use in obese women.
AB  - BACKGROUND: The objective of this systematic review is to determine whether obese
      women who use progestogen-only contraceptives are more likely to experience
      weight gain or serious adverse events as compared to nonobese users. STUDY
      DESIGN: We searched PubMed for all articles (in all languages) published in peer
      reviewed journals from database inception through October 2008, for evidence
      relevant to obesity and progestogen-only contraceptives. We used standard
      abstract forms and grading systems to summarize and assess the quality of the
      evidence. RESULTS: From 579 articles, we identified nine studies fitting our
      selection criteria. Evidence from five studies suggests that among adult women,
      baseline weight or body mass index is not associated with weight gain among depot
      medroxyprogesterone acetate (DMPA) users (Level II-2, Fair). Evidence from three
      studies suggests that among adolescent women, overweight or obese DMPA users may
      gain more weight than normal weight DMPA users or overweight/obese nonusers
      (Level II-2, Fair). Evidence from one small study of Norplant users showed no
      differences in weight gain by baseline weight (Level II-3, Poor). We did not
      identify studies of other progestogen-only contraceptive methods that examined
      weight change by baseline weight, nor did we identify studies that reported on
      any serious adverse events by baseline weight. CONCLUSIONS: Adolescent DMPA users
      who are obese may gain more weight than normal weight users. This observation was
      not seen in adult DMPA users or adolescent Norplant users.

PMID- 19751858
TI  - Use of combined oral contraceptives post abortion.
AB  - BACKGROUND: Providing combined oral contraceptives (COCs) following surgical or
      medical induced abortion offers women an opportune moment to initiate a reliable
      contraceptive method. STUDY DESIGN: We conducted a systematic review, searching
      MEDLINE and The Cochrane Library for articles in any language concerning COC use
      following spontaneous, induced (medical or surgical) or septic abortion, from
      1966 through June 2008. Seven articles were identified and evaluated using the
      United States Preventive Services Task Force system. RESULTS: Immediate COC
      initiation after first-trimester medical or surgical induced abortion did not
      increase side effects or prolong vaginal bleeding compared with use of a placebo,
      copper-bearing intrauterine device (IUD), nonhormonal contraceptive method or COC
      initiation at a later time. Initiating COCs after first-trimester surgical
      abortion produced small increases in coagulation parameters compared with IUD
      use; although they are statistically significant, their clinical relevance is
      unlikely. No study examined second-trimester induced or spontaneous abortion, or
      septic abortion. CONCLUSIONS: Evidence shows that COCs can be safely initiated
      immediately following surgical and medical abortion in the first-trimester of
      pregnancy.

PMID- 19751859
TI  - Combined oral contraceptive and intrauterine device use among women with
      gestational trophoblastic disease.
AB  - BACKGROUND: Women diagnosed with gestational trophoblastic disease (GTD) need
      safe and effective contraception because they are advised to delay a subsequent
      pregnancy. STUDY DESIGN: We searched MEDLINE and The Cochrane Library for
      articles in any language on use of combined oral contraceptives (COC), copper
      bearing or levonorgestrel-releasing IUDs among women with benign or malignant
      GTD, from database inception through November 2008. One review and nine articles
      were identified and evaluated. RESULTS: Incidence of postmolar trophoblastic
      disease was lower among COC users compared with nonusers in six studies, but
      higher among COC users in three studies. Five studies reported shorter human
      chorionic gonadotropin (hCG) regression duration among COC users compared with
      other methods. Development of postmolar trophoblastic disease did not differ
      significantly among IUD users compared with COC users or nonusers in three
      studies. CONCLUSIONS: Evidence shows that postmolar trophoblastic disease risk
      does not increase among women using COCs or an IUD following molar pregnancy
      evacuation compared with use of other contraceptive methods or no method.

PMID- 19751860
TI  - Oral contraceptives and family history of breast cancer.
AB  - BACKGROUND: Questions remain regarding whether oral contraceptive (OC) use among
      women with a family history of breast cancer increases disease risk. STUDY
      DESIGN: We conducted a systematic review by searching MEDLINE and CENTRAL
      databases for evidence (in all languages) published in peer-reviewed journals
      from 1966 to July 2008 that provided estimates of breast cancer risk according to
      family history. Twelve articles were identified and the quality of each study was
      assessed using the United States Preventive Services Task Force grading system.
      RESULTS: Results from 10 studies and one pooled analysis of 54 studies suggest
      that the use of OCs does not significantly modify the risk of breast cancer among
      women with a familial history of breast cancer; however, evidence from four
      studies shows that some women may be at a greater risk, particularly women who
      took OCs prior to 1975. CONCLUSIONS: Current evidence shows that women with a
      family history of breast cancer do not increase their disease risk by using OCs.

PMID- 19751861
TI  - The effects of hormonal contraceptive use among women with viral hepatitis or
      cirrhosis of the liver: a systematic review.
AB  - BACKGROUND: This report evaluates the effects of hormonal contraceptive use among
      women with viral hepatitis or cirrhosis of the liver. METHODS: PubMed and
      Cochrane databases were searched from inception to June 2008 for publications
      that examined the use of hormonal contraceptives among women with viral hepatitis
      or cirrhosis of the liver. RESULTS: Six studies met the inclusion criteria. In
      one study of acute hepatitis, combined oral contraceptive (COC) use did not
      affect duration of hospitalization or successful disease resolution. The
      remainder of the studies examined chronic hepatitis or its sequelae. Women
      recovered from hepatitis experienced transaminase elevation with COC use which
      resolved after 4 weeks in one study or increased slightly over 6 months in
      another study. Hepatitis B virus carriers using COCs had similar transaminase
      levels as nonusing carriers over 6 months. Studies of chronic hepatitis C
      infection demonstrated no influence of COC use on progression or severity of
      liver fibrosis or development of hepatocellular carcinoma. CONCLUSION: Data from
      one study suggest that COCs do not affect the course of acute hepatitis. Limited
      data from studies on chronic hepatitis or its sequelae suggest that COC use does
      not affect the rate of progression or severity of cirrhotic fibrosis, the risk of
      hepatocellular carcinoma in women with chronic hepatitis, or the risk of liver
      dysfunction in hepatitis B virus carriers.

PMID- 19751862
TI  - Hormonal contraceptive use among women with liver tumors: a systematic review.
AB  - BACKGROUND: The review was conducted to evaluate from the literature the safety
      of hormonal methods of contraception in women with liver tumors, specifically in
      benign and malignant disease. STUDY DESIGN: We searched PubMed and Cochrane
      databases to find all articles published from database inception through July
      2008 that were relevant to hormonal contraception use and liver tumors. RESULTS:
      Of 148 articles, three publications of two studies met the criteria for inclusion
      in this review; both investigated the use of hormonal contraception in women with
      the benign liver tumor focal nodular hyperplasia (FNH). In one small,
      retrospective case series, use of combined oral contraceptives (COCs) over a 4
      year average follow-up was not associated with a change in either the number or
      size of hepatic lesions. In another case series, use of either COCs or
      progestogen-only contraceptives (POCs) after FNH diagnosis had no influence on
      disease progression or resolution. CONCLUSIONS: The studies identified examined
      oral contraceptive use among women with FNH. We did not identify any studies of
      hormonal contraceptive use among women with hepatocellular adenoma or with
      malignant liver tumors. Limited, poor-quality evidence suggests that for women
      with FNH, use of low-dose COCs or POCs does not appear to influence either liver
      lesion resolution or progression.

PMID- 19751863
TI  - When can a woman have repeat progestogen-only injectables--depot
      medroxyprogesterone acetate or norethisterone enantate?
AB  - BACKGROUND: Currently, there is a generally accepted 2-week grace period for
      women returning early/late for reinjection of either depot medroxyprogesterone
      acetate (DMPA) or norethisterone enantate (NET-EN). This systematic review
      evaluates the evidence regarding return to fertility and ovulation after
      injection of a progestogen-only contraceptive. STUDY DESIGN: We searched the
      PubMed database to identify all relevant evidence published in peer-reviewed
      journals from database inception through November 2008 regarding timing of
      fertility and return to ovulation after the last injection of DMPA or NET-EN.
      RESULTS: We identified 20 articles, 10 on DMPA use, eight on NET-EN use and two
      examining both types of injectables. Six studies examining time to pregnancy
      after discontinuing DMPA or NET-EN reported that pregnancy rates during the
      currently recommended 2-week grace period were zero or very low. Studies of
      return to ovulation indicated a wide variation in time to ovulation post
      injection with the majority ranging from 15-49 weeks from the last injection (for
      DMPA) and 4.9-24.3 weeks from the last injection (for NET-EN). Limitations of
      this body of evidence include small sample sizes, lack of data on the main
      outcome of interest (time to pregnancy) and inconsistency in measurement of
      ovulation, a surrogate measurement for pregnancy risk. CONCLUSION: Studies
      evaluating time to pregnancy after last injection of DMPA or NET-EN reported
      extremely low pregnancy rates during the 2-week interval following the
      reinjection date; extremely low pregnancy rates for DMPA were also reported for 4
      weeks following the reinjection date. Studies of return to ovulation after last
      injection of DMPA generally found that the earliest ovulation did not occur until
      several months after the last injection while studies of NET-EN reported
      ovulations around (or even before) the time for reinjection.

PMID- 19751865
TI  - Preface: radiosurgery and radiotherapy for benign skull base tumors.

PMID- 19751866
TI  - The history of stereotactic radiosurgery and radiotherapy.
AB  - Stereotactic neurosurgery originated from the pioneering work of Horsley and
      Clarke, who developed a stereotactic apparatus to study the monkey brain in 1908.
      Spiegel and Wycis applied this technology to the human brain in 1947, which
      ultimately lead to the development of multiple stereotactic neurosurgical devices
      during the 1950s. It was Lars Leksell of Sweden, however, who envisioned
      stereotactic radiosurgery. Leksell developed the gamma knife to treat
      intracranial lesions in a noninvasive fashion. His work stimulated worldwide
      interest and created the field of stereotactic radiosurgery.

PMID- 19751867
TI  - Basic principles of radiobiology applied to radiosurgery and radiotherapy of
      benign skull base tumors.
AB  - Various types of ionizing radiation may be used therapeutically for benign skull
      base tumors. Treatment may involve single-dose radiosurgery, or may be
      fractionated into multiple doses. Designing and implementing a radiotherapy plan
      that maximizes the therapeutic ratio requires knowledge of the biophysical and
      radiobiological principles involved in these treatments. These basic
      radiobiological tenets are discussed in this chapter, with the focus on
      radiotherapy of benign skull base tumors. Animal and clinical data, however,
      acquired from the radiation of malignant tumors are necessarily included, as they
      comprise much of our knowledge of fractionation schedules, central nervous system
      (CNS) toxicity, and CNS volume effects.

PMID- 19751868
TI  - Radiation effects on the auditory and vestibular systems.
AB  - Definitive or postoperative radiation therapy (RT) is commonly used for the
      management of intracranial and extracranial head and neck tumors. Because of the
      variability of tumor location and dimensions, sparing of nontarget normal tissue
      and organs may not be possible. Treatment modalities that deliver the highest
      doses of radiation to the auditory system include stereotactic radiosurgery (SRS)
      and fractionated stereotactic radiotherapy (FSRT) for the treatment of vestibular
      schwannomas (VS), and fractionated radiotherapy (FRT) or intensity-modulated
      radiation therapy (IMRT) for the treatment of head and neck malignancies.
      Radiation therapy for VS is unique because of its involvement of the inner ear
      and preexisting auditory and vestibular dysfunction. Auditory and vestibular
      dysfunction following RT for VS may be limited by limiting the total dose of
      cranial nerve VIII irradiation and by fractionation.

PMID- 19751869
TI  - Gamma knife radiosurgery for vestibular schwannoma.
AB  - In 1951, Dr. Lars Leksell from Sweden conceived of what is now known as gamma
      knife radiosurgery (GKRS). Since Leksell first treated a patient who had a
      vestibular schwannoma in 1967, there has been a year-to-year increase in the
      number of patients treated with the gamma knife for vestibular schwannoma. This
      article outlines the technique of GKRS and discusses the current results of its
      use to treat vestibular schwannomas. Other topics discussed include tumor
      control, treatment of recurrent/residual and cystic vestibular schwannomas, and
      the results of treatment of neurofibromatosis type 2.

PMID- 19751870
TI  - Stereotactic radiotherapy for vestibular schwannoma.
AB  - Vestibular schwannomas are benign tumors of the Schwann cells of the eighth
      (VIII) cranial nerve. Precision radiotherapy techniques used to manage these
      tumors include stereotactic radiotherapy (SRT), which can be delivered with
      either a conventional or hypofractionated regimen. The radio-biologic rationale
      and reported clinical outcomes of patients treated with SRT are reviewed.

PMID- 19751871
TI  - Cyberknife radiotherapy for vestibular schwannoma.
AB  - Stereotactic radiosurgery is a well-established treatment modality for vestibular
      schwannoma. Initial reports using single-stage radiosurgery have demonstrated
      excellent tumor control rates. Many patients now elect to undergo radiosurgery
      given the potential for tumor control while avoiding the morbidity associated
      with microsurgical resection. In attempt to improve hearing preservation rates of
      single-state radiosurgery, staged frame-based radiotherapy using a 12-hour
      interfraction interval was used at the authors' institution and has shown a
      hearing preservation rate of 77% at 2 years of follow-up. With the arrival of the
      Cyberknife, a frameless, image-guided radiotherapy system, staged stereotactic
      radiotherapy for vestibular schwannoma became more practical. This article
      outlines the rationale and treatment protocols developed at Stanford University
      (California) and reports the authors' initial experience using the Cyberknife to
      treat vestibular schwannoma.

PMID- 19751872
TI  - Stereotactic radiosurgery and stereotactic radiotherapy in the treatment of skull
      base meningiomas.
AB  - Meningiomas are the most common nonglial brain tumors. They tend to be slow
      growing and benign and can reach substantial sizes before becoming symptomatic.
      Complete surgical resection of intracranial meningiomas remains the treatment of
      choice. Location of a meningioma within the cranial vault may make complete
      surgical resection unlikely; tumors arising from the dura of the skull base are
      particularly challenging. Advances in radiation therapy, including stereotactic
      techniques, can expand the options for treatment available in these situations.
      They may be used as adjuncts to surgery or as alternative modalities in the
      treatment of these complex tumors.

PMID- 19751873
TI  - Radiosurgery for glomus jugulare tumors.
AB  - Glomus jugulare tumors arise from adventitial chemoreceptor tissue in the jugular
      bulb. Although histologically benign, these tumors can be locally aggressive
      because of their proximity to the lower cranial nerves and major vascular
      structures. Traditional treatment involves microsurgical removal with or without
      endovascular embolization, but morbidity following total resection can result in
      injury to the facial and lower cranial nerves. Radiosurgery has recently emerged
      as a promising alternative to older therapeutic strategies for treatment of
      glomus jugulare tumors. This article reviews the latest benefits of radiosurgery
      and demonstrates how this modality represents an effective treatment option for
      glomus jugulare tumors with excellent tumor control and low risk for morbidity.
      In addition, this article will detail the role of minimally invasive sub-total
      resection of glomus jugulare tumors as a surgical complement to gamma knife
      therapy.

PMID- 19751874
TI  - Microsurgery after radiosurgery or radiotherapy for vestibular schwannomas.
AB  - Radiosurgery or radiotherapy for vestibular schwannomas has become a common
      practice with a high chance for tumor control. Despite the high rate of tumor
      control, there are some tumors that cannot be controlled with radiation therapy.
      Surgical treatment after radiosurgery or radiotherapy may be necessary for tumors
      that continue to grow, or for patients who develop brainstem compressive
      symptoms, disabling hemifacial spasm, or hydrocephalus. The House Ear Clinic (Los
      Angeles, California) experience with microsurgery after irradiation has
      demonstrated that the facial nerve is different once it has been radiated. An
      irradiated facial nerve's regeneration potential is diminished, and the recovery
      from microsurgical trauma is not as robust. It is recommended that patients who
      require microsurgical excision following radiosurgery or radiotherapy have a more
      conservative approach compared to non-irradiated cases.

PMID- 19751875
TI  - Neoplastic transformation after radiosurgery or radiotherapy: risk and realities.
AB  - In recent years, the use of radiosurgery or radiotherapy for benign brain tumors
      has increased significantly. Although long-term follow-up from several centers
      suggests that radiosurgery or radiotherapy is effective and safe, there are
      particular concerns regarding development of radiation-induced tumors. This
      article reviews the use of radiosurgery and fractionated radiation therapy with
      particular regard to new tumor induction and malignant transformation. The
      authors have found that the risk of radiation associated tumors after
      radiosurgery or radiotherapy for benign brain tumors is very low. All patients
      should be informed about the risks and consequences of radiation and
      microsurgery. The current practice standards for radiosurgery should not be
      modified because of this very low risk.

PMID- 19751876
TI  - Tubular invasion and the morphogenesis of tumor budding in colorectal carcinoma.

PMID- 19751877
TI  - Hep G2 is a hepatoblastoma-derived cell line.

PMID- 19751878
TI  - E-cadherin in solid pseudopapillary tumors of the pancreas--reply.

PMID- 19751879
TI  - Sebaceous lesions and their associated syndromes: part I.
AB  - Sebaceous neoplasms have long been a source of confusion to dermatologists and
      pathologists alike. Disagreements regarding nomenclature, classification, and
      management have been longstanding. Sebaceous lesions represent a broad spectrum
      of interesting entities that range from hamartomas, hyperplasias, and benign
      tumors to highly malignant neoplasms. This article discusses the clinical and
      pathologic features of sebaceous hyperplasia, nevus sebaceous of Jadassohn,
      sebaceous adenoma, seboacanthoma, sebaceous epithelioma, sebaceoma, mantleoma,
      basal cell carcinoma with sebaceous differentiation, sebomatricoma
      (sebomatrixoma), and sebaceous carcinoma. Controversies regarding these lesions
      will be explored, and any relationship with Muir-Torre syndrome will be
      discussed.

PMID- 19751880
TI  - Sebaceous lesions and their associated syndromes: part II.
AB  - Sebaceous lesions are associated with two syndromes with widespread multisystem
      disorders and tumors. Linear sebaceous nevus syndrome has been traditionally
      known as the triad of sebaceous nevus of Jadassohn, seizures, and mental
      retardation. This syndrome encompasses a much broader spectrum of multisystem
      disorders, which is explored below. Muir-Torre syndrome is described as the
      presence of sebaceous tumors or keratoacanthomas with an underlying visceral
      malignancy. It is caused by mutations in DNA mismatch repair genes. We discuss
      its relationship with Lynch syndrome and suggest a comprehensive algorithm on how
      to screen patients with sebaceous neoplasms for Muire-Torre syndrome. We also
      provide suggested intensive cancer screening guidelines based on recommendations
      for patients with Lynch syndrome that may also be of value for patients with Muir
      Torre syndrome.

PMID- 19751881
TI  - Local anesthesia using buffered 0.5% lidocaine with 1:200,000 epinephrine for
      tumors of the digits treated with Mohs micrographic surgery.
AB  - BACKGROUND: Several specialties and textbooks continue to advocate that local
      anesthesia using epinephrine should not be used during surgery involving the
      digits. OBJECTIVE: We sought to assess the association between local anesthesia
      (buffered 0.5% lidocaine and 1:200,000 epinephrine) injected into digits,
      comorbid patient conditions, and postoperative complications including ischemia
      or necrosis. METHODS: A retrospective review of all patients presenting for Mohs
      micrographic surgery in a private practice ambulatory surgery center was
      performed between October 2002 and January 2009. Patient factors including amount
      of anesthesia injected; preoperative vitals; history of hypertension, stroke, or
      circulatory disorders; and presence of anticoagulation were assessed. RESULTS:
      Three Mohs surgeons' patients were included in the study. No digital blocks were
      performed; local anesthesia was infiltrated directly into the tumor site.
      Patients received buffered 0.5% lidocaine plus epinephrine 1:200,000. Of 63
      patients presenting for surgery (59 fingers and 4 toes), there were no cases of
      digital ischemia or necrosis. Approximately one-third had a circulatory disorder
      or diabetes, and more than half had a diagnosis of hypertension or were taking
      anticoagulation. The average amount of anesthesia injected was 6.92 mL, with the
      greatest amount being 25 mL. LIMITATIONS: This was a retrospective review with
      possible overestimation of adverse effects as a result of referral bias of
      complicated patients to an ambulatory surgery center for treatment. CONCLUSION:
      There is no evidence that buffered 0.5% lidocaine with epinephrine 1:200,000
      causes ischemia or necrosis when injected into digits. This is true despite a
      history of circulatory disorders, thrombosis, diabetes, smoking, anticoagulation,
      or significant preoperative hypertension.

PMID- 19751882
TI  - Primary cutaneous cribriform apocrine carcinoma: a clinicopathologic and
      immunohistochemical study of 26 cases of an under-recognized cutaneous adnexal
      neoplasm.
AB  - BACKGROUND: Cribriform carcinoma is the histopathologic variant of cutaneous
      apocrine carcinoma characterized by interconnected solid aggregations of
      neoplastic cells that are punctuated by small round spaces. OBJECTIVE: To
      describe the histopathologic and immunohistochemical characteristics of this
      under-recognized cutaneous adnexal neoplasm. METHODS: Twenty-six cases of primary
      cutaneous cribriform apocrine carcinoma were clinically, histopathologically, and
      immunohistochemically studied. RESULTS: Seven neoplasms arose in males and 19 in
      females. The median age of the patients was 47.8 years. The lower and upper limbs
      were the most frequent sites. Histopathologically, the neoplasms consisted of
      well-circumscribed dermal nodules composed of multiple, interconnected, solid
      aggregations of basophilic epithelial cells that were punctuated by small round
      spaces. Immunohistochemically, the neoplastic cells expressed immunoreactivity
      for MNF116, AE1/AE3, Cam 5.2, cytokeratin 7, carcinoembryonic antigen, and
      epithelial membrane antigen. LIMITATIONS: All specimens came from
      dermatopathology laboratories, and some inherent selection bias may exist.
      CONCLUSIONS: Primary cutaneous cribriform apocrine carcinoma is a distinctive but
      little-known variant of cutaneous apocrine carcinoma.

PMID- 19751884
TI  - Histiocytoid Sweet syndrome.

PMID- 19751883
TI  - Selection criteria for genetic assessment of patients with familial melanoma.
AB  - Approximately 5% to 10% of melanoma may be hereditary in nature, and about 2% of
      melanoma can be specifically attributed to pathogenic germline mutations in
      cyclin-dependent kinase inhibitor 2A (CDKN2A). To appropriately identify the
      small proportion of patients who benefit most from referral to a genetics
      specialist for consideration of genetic testing for CDKN2A, we have reviewed
      available published studies of CDKN2A mutation analysis in cohorts with invasive,
      cutaneous melanoma and found variability in the rate of CDKN2A mutations based on
      geography, ethnicity, and the type of study and eligibility criteria used. Except
      in regions of high melanoma incidence, such as Australia, we found higher rates
      of CDKN2A positivity in individuals with 3 or more primary invasive melanomas
      and/or families with at least one invasive melanoma and two or more other
      diagnoses of invasive melanoma and/or pancreatic cancer among first- or second
      degree relatives on the same side of the family. The work summarized in this
      review should help identify individuals who are appropriate candidates for
      referral for genetic consultation and possible testing.

PMID- 19751885
TI  - Skin cancer meets vitamin D: the way forward for dermatology and public health.

PMID- 19751886
TI  - Blue (or purple) toes: chilblains or chilblain lupus-like lesions are a
      manifestation of Aicardi-Goutieres syndrome and familial chilblain lupus.

PMID- 19751887
TI  - A simple algorithm for evaluating dermatologic disease in critically ill
      patients: a study based on retrospective review of medical intensive care unit
      consults.

PMID- 19751888
TI  - Disseminated pyoderma gangrenosum: role for vascular endothelial growth factor
      and hypoxia inducible factor-2.

PMID- 19751889
TI  - Human resources, training, and the growing worldwide epidemic of kidney disease:
      introduction.

PMID- 19751890
TI  - Creating research infrastructure and functionality to address chronic kidney
      disease: the Kidney Research Institute.
AB  - An expanding proportion of people in the United States and worldwide are affected
      by kidney disease, leading to a growing concern over the public health
      implications. Despite the high prevalence and the considerable associated health
      risks of kidney disease, major gaps in our knowledge base hinder the delivery of
      optimal medical care to affected individuals. Moreover, research progress that
      translates into clinical benefit has been slow. For example, over the past 20
      years, there has been no successful implementation of a new therapeutic agent
      specifically designed for the treatment of glomerular diseases, which in part
      explains why glomerular diseases remain the leading cause of kidney disease in
      the United States and worldwide. Similarly, the limitations of current approaches
      to dialysis as treatment of end-stage kidney disease are becoming more apparent,
      with marginal improvements in risks for hospitalization or mortality over time.
      Along with recognition of changes in the public health burden of kidney disease,
      and perception of limited progress in the clinical treatment of kidney disease, a
      change in kidney disease research is now underway. We are entering a new era in
      biomedicine emphasizing interdisciplinary and translational research. We here
      delineate the purpose, mission, and goals, and describe the evolving vision,
      infrastructure, and research platform of a new Kidney Research Institute,
      designed to overcome barriers to researching improvements in effective clinical
      care.

PMID- 19751891
TI  - Analysis of multidisciplinary care models and interface with primary care in
      management of chronic kidney disease.
AB  - Public policy efforts and education have led to an increased appreciation of the
      prevalence of chronic kidney disease (CKD) in general outpatient populations. The
      complexity of the care of individuals with established CKD has led to the
      development of multidisciplinary care models, which have been shown to improve
      the clinical outcomes of those with CKD. The interface between specialty and
      primary care in various systems remains necessary and desired, albeit a
      continuing challenge. This overview reviews various models of specialty care for
      CKD patients, including those that emphasize multidisciplinary team approaches,
      and highlight the essential role(s) of primary care physicians. Importantly,
      there is a need for improved definition of CKD populations and individuals,
      review and refinement of proposed care pathways, and the need to define essential
      elements of care for the patient. Models of care often are not subject to the
      same rigor that other interventions applied to this population are; nonetheless,
      we offer here a framework for establishing and evaluating care models for the CKD
      populations at various stages of disease and with various comorbidities.

PMID- 19751892
TI  - The UK model for system redesign and chronic kidney disease services.
AB  - The British National Health Service is a closed managed care system. This single
      health care system for the United Kingdom is funded by the government and paid
      for by general taxation. All UK citizens are registered with primary care
      physicians who control access to secondary care services. As a managed care
      system it should be able to offer integrated care across the whole patient
      pathway. In reality there are professional, organizational, and institutional
      barriers to coordination and delivery of care in the NHS. Historically, the
      United Kingdom has been among the lowest health care spenders of organizations
      for economic cooperation in developed countries, in absolute terms as well as
      proportion of the gross domestic product. However, since a Government pledge to
      place quality at the heart of the NHS and a commitment in 2000 to increase
      spending on the NHS, the NHS budget has more than doubled-an unprecedented rate
      of growth, roughly by 7.5% annually in real terms. A quality and outcomes
      framework has been introduced into primary care to systematically incentivize
      process measures such as computerization and chronic disease management by
      establishing practice-based disease registers. The strategic planning for kidney
      services in England has been developed in this national environment complemented
      by local research findings and the wider international consensus that has emerged
      since the publication of the classification of chronic kidney disease in 2002.
      This program of work has resulted in a paradigm shift from kidney disease being
      viewed as a secondary care condition to being a primary care priority as part of
      vascular disease control and management. In the first 2 years of the initiative
      more than 40% of the expected chronic kidney disease stage 3 to 5 population have
      been registered in primary care. Kidney disease now is recognized as a public
      health problem in the United Kingdom, preventative strategies are being
      integrated into comprehensive vascular risk assessment and management programs,
      and kidney disease has become an NHS priority area.

PMID- 19751893
TI  - Chronic kidney disease epidemic: cost and health care implications in China.
AB  - Chronic kidney disease is growing as a global public health problem. With more
      than 1.3 billion people, China is the world's largest and most populous country.
      Understanding the epidemiology of chronic kidney disease in China could be
      helpful to predict its impact on the health care system and to establish
      comprehensive strategies to reduce its burden.

PMID- 19751894
TI  - Current status of chronic kidney disease care in southeast Asia.
AB  - Chronic kidney disease (CKD) is a major health problem for the underdeveloped
      countries of southeast Asia, home to more than 2 billion people. The true
      incidence and prevalence in the region is not known, but estimates suggest that
      the prevalence may be more than that reported in Western societies. The majority
      of affected individuals are young and in the most productive years of their
      lives. The looming epidemic of diabetes and hypertension is likely to further add
      to the disease burden. A high prevalence has been reported from some regions,
      suggesting the presence of unique etiologic factors. A large proportion of
      patients present late, with advanced kidney failure and multiple complications.
      Management is hampered by the lack of health care services, especially in the
      rural areas. The health care expenditure by the governments in these countries is
      very low, and there are no regional or national policies for chronic disease
      management including CKD. There is a major shortage of trained nephrologists. In
      absence of any government or private reimbursement, most patients cannot afford
      the high treatment cost. Renal replacement therapy is available only to a
      minority. The practice of dialysis in the region is not standardized and a large
      number of patients develop complications. There is an urgent need to develop CKD
      detection and prevention programs. Investigations are required to characterize
      the unique etiologic factors in different geographic regions so that prevention
      programs can be targeted appropriately. Cost-cutting strategies would make renal
      replacement therapy accessible to the general population. According sufficient
      prominence to CKD in education programs would help increase awareness.

PMID- 19751896
TI  - Obesity and chronic kidney disease.
AB  - This article summarizes the current hypotheses that link visceral obesity and
      kidney malfunction and provides information on the epidemiology and renal
      pathology resulting from visceral obesity.

PMID- 19751895
TI  - Interaction of aging and chronic kidney disease.
AB  - Our goals in this review are to describe what is known about the prevalence and
      clinical implications of non-dialysis-dependent chronic kidney disease in the
      elderly and to discuss some of the most common challenges to managing older
      patients with chronic kidney disease.

PMID- 19751897
TI  - Can comprehensive lifestyle change alter the course of chronic kidney disease?
AB  - Comprehensive lifestyle change can impact health favorably in many domains, from
      prevention and treatment of various diseases to improved functional status and
      quality of life. Although habitual behaviors clearly influence chronic kidney
      disease (CKD), lifestyle change often is not stressed in the clinical setting.
      The purpose of this review is to provide a critical appraisal of the scientific
      basis for effects of lifestyle on CKD and practical strategies that promote
      healthy behaviors. This review begins with a clinical case presentation to
      provide context for the scientific discussion. Dietary composition of
      macronutrients, particularly protein intake, is highlighted. Clinical evidence is
      presented for avoiding protein excess, a contemporary problem in the typical
      overeating environment of the developed world. Concomitant approaches to
      balancing intake of carbohydrates and fats also are presented. Integration of
      sodium reduction with macronutrient adjustment is reviewed within the framework
      of managing blood pressure in the setting of CKD. Considering the emerging body
      of evidence for obesity-related CKD and associated complications, weight control
      is addressed from the standpoint of decreasing calories and increasing exercise.
      Finally, effects of smoking and alcohol use on CKD are discussed. In the spirit
      of active participation, which is essential to lifestyle change, the discussion
      returns full circle to a concluding statement from the clinical case patient who
      provides his point of view on lifestyle change while living with CKD.

PMID- 19751898
TI  - Economic evaluation of dialysis therapies.
AB  - The prevalence of end-stage renal disease continues to increase globally, and
      most patients are treated with dialysis. Despite technological advances in
      dialysis care, the relatively high costs of providing dialysis have not decreased
      substantially over the past 4 decades. These 2 factors are a significant concern
      in this era of fiscal restraint and finite health care budgets. Economic
      evaluation of dialysis treatment consistently has shown that home-based
      hemodialysis and peritoneal dialysis are less costly than in-center hemodialysis.
      Although only a portion of patients may be eligible for this therapy, current use
      in Canada and the United States suggests that significantly more patients could
      be treated with these therapies, which would result in significant cost savings
      without compromising patient outcomes. There is some evidence to suggest that the
      modality of home nocturnal dialysis may offer improvements in clinical outcomes
      including quality of life, but further study of the cost effectiveness of this
      modality is required.

PMID- 19751899
TI  - Is living kidney donation the answer to the economic problem of end-stage renal
      disease?
AB  - The escalating number and cost of treating patients with end-stage renal disease
      is a considerable economic concern for health care systems and societies
      globally. Compared with dialysis, kidney transplantation leads to improved
      patient survival and quality of life, as well as cost savings to the health
      payer. Despite efforts to increase kidney transplantation, the gap between supply
      and demand continues to grow. In this article we explore the economic
      consideration of both living and deceased transplantation. Although living kidney
      donation has several advantages from an economic perspective, efforts to increase
      both deceased and living donation are required. Strategies to increase kidney
      donation are underfunded, and even costly strategies are likely to lead to net
      health care savings. However, demonstration of efficacy of these strategies is
      required to ensure efficient use of resources.

PMID- 19751900
TI  - The chronic kidney disease epidemic: a challenge for nephrology training
      programs.
AB  - A major challenge facing the nephrology community in the United States is the
      training of adequate numbers of nephrologists to meet patient care and research
      needs. There is particular cause for concern because of the increasing incidence
      and prevalence of patients with chronic kidney disease. Data on the clinical and
      research nephrology workforce are incomplete or absent. However, the number of
      such individuals likely is inadequate to meet current and projected needs. To
      solve these workforce shortages, significant issues with regard to clinical and
      research training need to be addressed. These include funding of fellowship
      training, increasing the pipeline of medical students and internal medicine
      residents, and enhancing interest in nephrology among international and
      particularly US medical graduates. This review discusses these challenges facing
      the renal community, with emphasis on the care, prevention, and treatment of
      chronic kidney disease, and identifies potential pathways to developing
      solutions.

PMID- 19751901
TI  - Differentiation: a stem cell journal and more.

PMID- 19751903
TI  - Collagens in the Alzheimer's disease news--again.

PMID- 19751902
TI  - A home away from home: challenges and opportunities in engineering in vitro
      muscle satellite cell niches.
AB  - Satellite cells are skeletal muscle stem cells with a principal role in postnatal
      skeletal muscle regeneration. Satellite cells, like many tissue-specific adult
      stem cells, reside in a quiescent state in an instructive, anatomically defined
      niche. The satellite cell niche constitutes a distinct membrane-enclosed
      compartment within the muscle fiber, containing a diversity of biochemical and
      biophysical signals that influence satellite cell function. A major limitation to
      the study and clinical utility of satellite cells is that upon removal from the
      muscle fiber and plating in traditional plastic tissue culture platforms, their
      muscle stem cell properties are rapidly lost. Clearly, the maintenance of stem
      cell function is critically dependent on in vivo niche signals, highlighting the
      need to create novel in vitro microenvironments that allow for the maintenance
      and propagation of satellite cells while retaining their potential to function as
      muscle stem cells. Here, we discuss how emerging biomaterials technologies offer
      great promise for engineering in vitro microenvironments to meet these
      challenges. In engineered biomaterials, signaling molecules can be presented in a
      manner that more closely mimics cell-cell and cell-matrix interactions, and
      matrices can be fabricated with diverse rigidities that approximate in vivo
      tissues. The development of in vitro microenvironments in which niche features
      can be systematically modulated will be instrumental not only to future insights
      into muscle stem cell biology and therapeutic approaches to muscle diseases and
      muscle wasting with aging, but also will provide a paradigm for the analysis of
      numerous adult tissue-specific stem cells.

PMID- 19751904
TI  - Microscopic thrombi in glioblastoma multiforme do not predict the development of
      deep venous thrombosis.
AB  - Patients with glioblastoma multiforme (GBM) are known to be at risk for
      hypercoagulable events. Tumoral intravascular thrombi likely contribute to the
      development of hypoxia and necrosis. The purpose of this study was to assess
      whether there is a relationship between the number of thrombi identified
      microscopically at the time of tumor resection and the subsequent development of
      extremity deep venous thrombosis (DVT). A retrospective review of 96 patients (53
      men and 43 women; age range, 21-92 years; mean age, 60.2 years) with GBM (World
      Health Organization grade IV) was carried out. Thrombi were counted (number of
      thrombi/blood vessels evaluated/10 high-power fields) in nonnecrotic areas of the
      resected tumor and correlated with a variety of clinical and pathological
      parameters, including the development of postoperative DVT, as detected by
      extremity ultrasound. Thrombi were identified in the resected GBM in 66 (69%)
      patients. Of the tumors with thrombi, the percentage of blood vessels with
      thrombi ranged from 1.1% to 42.9% (mean, 10.7%). Deep venous thrombosis was
      discovered in 30 (31.3%) patients. There was no correlation between the number of
      microscopic thrombi and the development of DVT. Eighty-one patients died of tumor
      (survival, 1-66 months; mean, 11.0 months), 12 patients were alive at last known
      follow-up (mean, 23 months), and 3 patients were lost to follow-up. Of patients
      with DVT, 27 patients died of tumor (survival, 1-47 months; mean, 11.0 months), 3
      patients were alive (18, 20, and 21 months), and 1 patient was lost to follow-up.
      There was no correlation between the number of microscopic thrombi and the
      percentage of resected tumor that was necrotic (range, <5%-90%), presence of
      palisaded necrosis (36.8% of tumors), presurgical (mean, 78.3) or postsurgical
      (mean, 75.5) Karnofsky performance scores, or survival (mean, 8.9 months in
      patients with no microscopic thrombi vs 11.5 months in patients with thrombi).
      Microscopic thrombi were identified in about two thirds (69%) of patients with
      GBM, and DVT developed in about one third (31.3%) of patients with GBM. There was
      no correlation between the number of microscopic thrombi and the subsequent
      development of DVT in patients with GBM. Patients who developed DVT did not
      appear to have a worse survival.

PMID- 19751905
TI  - Asbestosis: demonstration of distinctive interstitial fibroelastosis: a pilot
      study.
AB  - Asbestosis has long been defined as a diffuse interstitial "fibrotic" process, in
      similarity to other chronic interstitial pulmonary diseases. To address the
      hypothesis (which was based on morphological nuances) that the interstitial
      connective tissue response in asbestosis may be fibroelastotic rather than
      fibrotic, a comparative characterization of the connective response in cases of
      asbestosis and other forms of interstitial lung disease was performed. Archival
      open lung biopsies or autopsy specimens of pulmonary diseases featuring
      interstitial connective tissue abnormalities (15 of asbestosis, 21 of organizing
      pneumonia, 15 usual interstitial pneumonitis/idiopathic pulmonary fibrosis [IPF],
      9 organizing diffuse alveolar damage, 9 "nonspecific" interstitial pneumonitis, 4
      sarcoidosis, 3 each of desquamative interstitial pneumonia and chronic amiodarone
      toxicity, 2 cryptogenic organizing pneumonias, and 1 each of chronic
      hypersensitivity pneumonitis and chronic eosinophilic pneumonitis [85 total])
      were stained histochemically with hematoxylin and eosin, Perl's method, Gomori's
      trichrome procedure, and the Verhoeff-van Gieson technique. Representative
      subsets of the cases (n = 20) were also studied immunohistologically using an
      antibody to elastin. Fibroelastosis in each of the samples was assessed for the
      degree of response and its location using a 3-tiered scale. The degree of
      fibroelastosis in the 15 cases of asbestosis was variable, with the pattern being
      peribronchial and perivascular in all instances; at least 2 asbestos bodies were
      identified in fibroelastotic foci in each of the 15 cases as highlighted with
      Perl's stain. Forty-seven cases of nonasbestotic lung disease (71%) showed
      interstitial fibrosis with a variable (usually modest) amount of admixed elastic
      tissue; when present, elastic fibers were distributed in a diffuse interstitial
      pattern, with or without perivascular accentuation. All cases of IPF also showed
      areas of fibroelastosis, but those foci were confined to regions of overt
      "honeycomb" change. No asbestos bodies were seen in any disease except
      asbestosis, and a predominantly peribronchial pattern of fibroelastosis was not
      identified in any nonasbestotic interstitial lung disease in this study. The
      authors conclude that the types and patterns of pulmonary connective tissue
      response in interstitial lung diseases may provide additional diagnostic clues to
      the presence of asbestosis.

PMID- 19751906
TI  - Nucleoporin 88 expression in normal and neoplastic squamous epithelia of the
      uterine cervix.
AB  - This study investigated the expression of nucleoporin 88 (Nup88) in formalin
      fixed, paraffin-embedded archival tissues of cervical specimens consisting of
      normal ectocervical squamous epithelia (n = 34), low-grade squamous
      intraepithelial lesions corresponding to cervical intraepithelial neoplasia (CIN)
      1 (n = 9), high-grade squamous intraepithelial lesions corresponding to CIN2 and
      CIN3 (n = 28), and invasive squamous cell carcinoma (ISCC; n = 30) to determine
      whether expression of this factor is involved in the progression of the
      morphological spectrum from normal cervical epithelia to CIN and cervical ISCC. A
      standard immunohistochemical technique was performed using a Ventana BenchMark XT
      immunostainer with a mouse antihuman monoclonal antibody to Nup88. Immunostaining
      was scored with regard to quantity and intensity of positively stained cells,
      with final immunoscores from 0 to 12 in each case. Nucleoporin 88 immunoscores
      increased significantly from normal ectocervical squamous epithelia to CIN1,
      CIN2/3, and ISCC (P < .0001, analysis of variance). Cervical intraepithelial
      neoplasia 2/3 as isolated lesions and adjacent to ISCC did not differ
      significantly. A significant correlation was noticed for immunoscores of CIN2/3
      adjacent to ISCC and the corresponding ISCC (P = .0007). This study indicates
      that Nup88 is significantly overexpressed in high-grade CIN lesions and ISCC
      compared with normal ectocervical squamous epithelia and CIN1. However, Nup88
      evaluation is of limited value as a diagnostic marker in individual cases.

PMID- 19751907
TI  - Comparative analysis of the expression of proliferating cell nuclear antigen,
      p53, bax, and bcl-2 in oral lichen planus and oral squamous cell carcinoma.
AB  - Several epidemiologic studies have shown the malignant transformation potential
      of oral lichen planus; however, this potential is subject of much controversy. To
      evaluate the expression of proteins related to the cell proliferation and
      apoptosis processes in oral lichen planus, we compared oral lichen planus with
      oral squamous cell carcinoma. Twenty-four cases of each lesion were submitted
      according to streptavidin-biotin technique to evaluate the immunohistochemical
      expression of proliferating cell nuclear antigen, p53, bax, and bcl-2 proteins.
      chi(2) test showed no statistically significant differences between the
      expression of p53, bax, and bcl-2 in oral lichen planus and oral squamous cell
      carcinoma (P > .05). However, the expression of proliferating cell nuclear
      antigen was significantly lower in oral lichen planus than in oral squamous cell
      carcinoma (P < .05). No statistically significant differences between the
      expression of p53, bax, and bcl-2 in oral lichen planus and oral squamous cell
      carcinoma were observed, which may be an evidence of the potential of malignant
      transformation of oral lichen planus.

PMID- 19751908
TI  - Predictive value of cyclooxygenase 2 and Bcl-2 for cervical lymph node metastasis
      in mucoepidermoid carcinoma.
AB  - The expression of cyclooxygenase 2 (COX-2) is induced by growth factors, tumor
      promoters, and cytokines. It is correlated with carcinogenesis and apoptosis
      inhibition. This study was designed to investigate the expression of COX-2 and
      BCl-2 and to correlate their expressions with the clinicopathologic features in
      the mucoepidermoid carcinoma (MEC). The expression of COX-2 and BCl-2 proteins
      was investigated in 16 archival tumor tissues of MEC using the streptavidin
      biotin complex technique. Clinical information was obtained through the
      computerized retrospective database from the tumor registry between 2001 and
      2007. It revealed that grading system of MEC did not correlate with the presence
      or absence of node metastasis. The expression of COX-2 and BCl-2 was variably
      expressed in all the examined specimens. COX-2 and BCl-2 immunoreactivity was
      observed mainly in the cytoplasm of neoplastic cells. As regard the
      clinicopathologic parameters, there was no significant difference in expression
      rates of COX-2 in patients among age, sex, and MEC grades (P > .05). However, the
      expression of COX-2 in node-positive tumors was significantly higher than that of
      node-negative tumors (P = .001). For BCL-2 expression, there was no significant
      difference in expression rates of BCl-2 in patients among age, sex, site,
      clinical stage, and lymph node metastasis (P > .05), whereas a high significant
      difference was observed between BCl-2 staining index and MEC grades (P = .027).
      Moreover, there is a positive correlation between COX-2 expression and BCL-2
      staining index (P = .000). COX-2 is a good predictor for lymph node metastasis as
      well as ideal therapeutic target for the prevention or treatment of MEC. BCl-2
      and COX-2 are potentially useful prognostic markers for MEC.

PMID- 19751909
TI  - Adapting lean to histology laboratories.
AB  - Histology laboratories (histolabs) can increase productivity and reduce
      turnaround time and errors by using any one of several available management
      tools. After a few years of operation, all histolabs develop workflow problems.
      Histology laboratories handling more than 20,000 cases per year benefit the most
      from implementing management tools, as occurred in the 25 facilities summarized
      in this article. Discontinuous workflow, lack of "pulling" between steps,
      accepting unavoidable waiting times while working with small batches within work
      cells, and a workflow with an uneven rate of completion, are some of the
      adaptations required by the Lean system when it is used in histology because 70%
      of the tasks are manual and the flow has to be interrupted to add value to the
      pieces of tissue during tissue processing, no matter how short that step is.
      After all these adaptations are incorporated, the histolab becomes as "Lean" as
      it can be, and the qualifier is also a recognition of the effort and personnel
      involvement in the implementation. Given its service nature, productivity
      increments do not expand the histolab customer base and could lead to staffing
      reductions. This is one of the causes of reluctance by some employees for
      implementing these techniques which are mostly driven by cost reductions sought
      by insurance companies and administrators, and not necessarily because of a real
      medical need to reduce the turnaround time. Finally, any histolab wanting to
      improve its workflow can follow some easy steps presented here as a guide to
      accomplish that objective. These steps stress the need for the supervisors to
      insure that the personnel in the histology laboratory are being paid at a
      comparable rate as other histolabs in the area.

PMID- 19751910
TI  - Sclerosing rhabdomyosarcoma of the parotid gland in an adult.
AB  - Primary rhabdomyosarcoma of salivary glands is an extremely rare neoplasm, mostly
      seen in children. A newly described subtype of rhabdomyosarcoma, sclerosing
      rhabdomyosarcoma, has not yet been reported in this location. We report on a
      parotid gland tumor characterized by infiltrative growth of primitive type of
      neoplastic cells showing strong and diffuse nuclear positivity for MyoD1 and
      myogenin and by prominent hyalinized/chondroid matrix with some myxoid foci. The
      tumor recurred several times, and in recurrent tumors, differentiation into strap
      myoid cells appeared. There were no distant metastases during the 5-year follow
      up. Sclerosing rhabdomyosarcoma may cause differential diagnostic problems
      because it could be confounded for osteosarcoma, chondrosarcoma, and some other
      types of sarcoma, and as in our case, for myxofibrosarcoma and myoepithelial
      carcinoma. Its location in the head and neck is of special interest because 6 of
      14 previously described adult cases of sclerosing rhabdomyosarcoma and 7 of 18
      pediatric cases also occurred in this region. To our knowledge, this is the first
      reported case of primary sclerosing rhabdomyosarcoma of the parotid gland.

PMID- 19751911
TI  - Solitary fibrous tumor of the pancreas.
AB  - A 67-year-old woman was found to have an incidental pancreatic mass on computed
      tomographic examination of her abdomen in the course of investigation of
      hematuria. The radiologic features were of a hypervascular mass in the uncinate
      process of the head of the pancreas, and a preoperative diagnosis of a
      neuroendocrine tumor was favored. A Whipple procedure was performed. The uncinate
      process contained a 2.6-cm well-circumscribed mass. Histologic evaluation showed
      a lesion composed of alternating hypercellular areas made up of spindle-shaped
      cells and hypocellular areas with hyalinized, keloidal-like fibrous tissue.
      Occasional dilated vascular channels and entrapped pancreatic tissue were present
      within the lesion. Immunohistochemistry showed the lesion to be CD34, CD99, and
      bcl-2 positive. No evidence of atypia was noted, and the overall impression was
      of a benign solitary fibrous tumor of the pancreas. This is an unusual primary
      spindle cell neoplasm of the pancreas and should be considered in the
      differential diagnosis of all spindle cell lesions that occur in the pancreas.

PMID- 19751912
TI  - Verrucous carcinoma of the cervix in a case with uterine prolapse.
AB  - Verrucous carcinoma of the female tract is rare. We present a case involving
      association of verrucous carcinoma of the cervix with uterine prolapse. A 86-year
      old woman was admitted with postmenopausal vaginal bleeding. The gynecologic
      examination revealed the uterine prolapse with a exophytic tumorous mass (3 x 6 x
      8 cm) on the cervix. A punch biopsy was taken from the tumor, which revealed
      coilocytotic and mild dysplastic changes in the squamous epithelium; invasion of
      the underlying stroma could not be evaluated. A cervical swab was tested for
      human papillomavirus (HPV) DNA using the polymerase chain reaction, and HPV type
      31 was detected. The tumorous mass was totally excised. The histopathologic
      diagnosis was consistent with verrucous carcinoma of the cervix: exophytic lesion
      was composed of thickened, acanthotic papillary squamous epithelium with mild
      dysplasia and diffuse parakeratosis, and no obvious invasion was observed. The
      patient was periodically controlled by pelvic examination and was free of
      progressive disease at 6 months. The diagnosis and treatment of verrucous
      carcinoma of the cervix may be difficult in some cases. The presence of HPV type
      31 in our case might indicate the possibility that HPV is the etiology of this
      neoplasm.

PMID- 19751913
TI  - Monotypic epithelioid angiomyolipoma of the adrenal gland: an unusual site for a
      rare extrarenal tumor.
AB  - Epithelioid angiomyolipoma (AML) is an uncommon renal mesenchymal tumor with
      malignant potential and is frequently associated with tuberous sclerosis.
      Extrarenal AMLs are rare, and to the best of our knowledge, this is the first
      reported case of a primary monotypic epithelioid AML of adrenal gland in a
      patient without evidence of tuberous sclerosis. The patient is a 42-year old man
      who presented with retroperitoneal hemorrhage resulting from spontaneous rupture
      of adrenal mass. Histologically, the tumor showed a prominent component of
      epithelioid smooth muscle cells with slightly pleomorphic nuclei, sometimes with
      prominent nucleoli and eosinophilic cytoplasm resembling oncocytic tumors.
      Epithelioid cells were positive for melanoma (HMB45 and positive MelanA) and
      smooth muscle markers (alpha-smooth muscle-specific actin), but not for
      epithelial markers (cytokeratin, EMA). Differential diagnosis from renal cell
      carcinoma, adrenal gland carcinoma, and metastatic carcinoma is often challenging
      because of its epithelioid morphology. Because primary and secondary malignant
      tumors are much more common and aggressive neoplasms, establishing the correct
      diagnosis has important therapeutic and prognostic implications.

PMID- 19751914
TI  - Wegener's granulomatosis of the breast: a rare entity with daily clinical
      relevance.
AB  - Wegener's granulomatosis (WG) is frequently diagnosed based on respiratory and
      renal manifestations. Breast involvement is rare. To date, approximately 27 cases
      of breast involvement by WG have been published. Most cases present in women
      between the third and seventh decades are unilateral and are accompanied by
      systemic manifestations of the disease. Although breast tissue is rarely affected
      by WG, the clinical presentation of these lesions requires that breast carcinoma
      be excluded from the clinical differential diagnosis. This publication is the
      most extensive review of the entity in the English literature in the last 3
      decades.

PMID- 19751915
TI  - Treatment effects of Memantine on language in moderate to severe Alzheimer's
      disease patients.
AB  - BACKGROUND: Language impairment is one of the most troublesome manifestations of
      Alzheimer's disease (AD). The objective of this post hoc analysis was to assess
      the treatment effects of Memantine on language in patients with moderate to
      severe AD, using the recently developed Severe Impairment Battery-Language (SIB
      L) scale. METHODS: From a combined database including four Memantine clinical
      trials in moderate-to-severe AD, we analyzed 801 patients with SIB-L scores of
      <38 and Mini-Mental State Examination scores of <15. Patients were treated with
      either 20 mg Memantine per day or placebo. Mean changes in SIB-L scores from
      baseline were calculated. For responder analyses, a change in SIB-L score greater
      than or equal to the SIB-L measurement error of 3.7 points was considered a
      clinically relevant response. RESULTS: The mean change from baseline in SIB-L
      score at week 12 and weeks 24/28 (study end) significantly favored Memantine over
      placebo treatment (P < .0001 and P = .0182, respectively). Overall, more
      Memantine-treated patients than placebo-treated patients benefited from
      treatment. The effect was especially pronounced in patients with substantial
      language impairment on the SIB-L (baseline score, <or=20). At weeks 24/28,
      significantly more Memantine-treated patients experienced a clinically relevant
      improvement (25.4% vs. 10.8%, P = .0414), and significantly fewer patients
      experienced clinically relevant worsening (32.8% vs. 60.0%, P = .0029).
      CONCLUSIONS: Memantine treatment of AD patients results in significant benefits
      for language function. Our results suggest that it is worth considering this
      therapeutic option, even for AD patients with marked language impairment.

PMID- 19751916
TI  - Severe Impairment Battery Language scale: a language-assessment tool for
      Alzheimer's disease patients.
AB  - BACKGROUND: Communication problems are common in Alzheimer's disease (AD)
      patients, but instruments to assess these symptoms are limited. Our objective was
      to create a new scale, based on the language subscale of the Severe Impairment
      Battery (SIB), as a sensitive and reliable measurement of treatment effects on
      language performance. METHODS: All 24 items of the SIB language subscale were
      chosen for analysis. Baseline scores of 1320 moderate-to-severe patients (Mini
      Mental State Examination [MMSE] score, <15), from a combined AD database of four
      Memantine clinical trials (Study Codes: IE-2101, MEM-MD-01, MEM-MD-02, and MRZ
      9605), were used for item reduction according to a standard principal components
      factor analysis. All items with loadings >0.5 on the identified factors were
      selected for inclusion in the new language scale. Correlations with existing AD
      scales were examined. RESULTS: The analysis indicated six factors, with 21 of 24
      items showing loadings >0.5. The resulting 21-item SIB Language (SIB-L) scale
      exhibited high internal consistency (Cronbach's alpha = 0.809). The maximal SIB-L
      score was 41 points, with a measurement error of 3.7 points. The stratification
      of baseline SIB-L scores (mean, 31.7; SD, 8.4) by MMSE scores (mean, 9.7; SD,
      3.3) showed a high variance in SIB-L scores. This confirms that patients with a
      low MMSE score can possess preserved language abilities. The SIB-L scale did not
      exhibit substantial floor-and-ceiling effects. CONCLUSIONS: The new SIB-L is a
      fast (<15 minutes) and easily administered scale with favorable psychometric
      characteristics for assessing language impairment and treatment effects on the
      language performance of patients with moderate to severe AD.

PMID- 19751917
TI  - "Below average" self-assessed school performance and Alzheimer's disease in the
      Aging, Demographics, and Memory Study.
AB  - BACKGROUND: A low level of formal education is becoming accepted as a risk factor
      for Alzheimer's disease (AD). Although increasing attention has been paid to
      differences in educational quality, no previous studies addressed participants'
      own characterizations of their overall performance in school. We examined whether
      self-assessed school performance is associated with AD beyond the effects of
      educational level alone. METHODS: Participants were drawn from the population
      representative Aging, Demographics, and Memory Study (ADAMS, 2000-2002). The
      ADAMS participants were asked about their performance in school. Possible
      response options included "above average," "average," or "below average." The
      ADAMS participants also underwent a full neuropsychological battery, and received
      a research diagnosis of possible or probable AD. RESULTS: The 725 participants
      (mean age, 81.8 years; 59% female; 16% African-American) varied in self-assessed
      educational performance: 29% reported "above average," 64% reported "average,"
      and 7% reported "below average" school performance. Participants with a lower
      self-assessed school performance had higher proportions of AD: 11% of
      participants with "above average" self-assessed performance had AD, as opposed to
      12% of participants with "average" performance and 26% of participants with
      "below average" performance (P < 0.001). After controlling for subjects' years in
      school, a literacy test score (Wide-Range Achievement Test), age, sex,
      race/ethnicity, apolipoprotein E-epsilon4 status, socioeconomic status, and self
      reported comorbidities, respondents with "below average" self-assessed school
      performance were four times more likely to have AD compared with those of
      "average" performance (odds ratio, 4.0; 95% confidence interval, 1.2-14). "Above
      average" and "average" self-assessed school performance did not increase or
      decrease the odds of having AD (odds ratio, 0.9; 95% confidence interval, 0.5
      1.7). CONCLUSIONS: We suggest an association between "below average" self
      assessed school performance and AD beyond the known association with formal
      education. Efforts to increase cognitive reserve through better school
      performance, in addition to increasing the number of years of formal education in
      early life, may be important in reducing vulnerability throughout the life
      course.

PMID- 19751918
TI  - Current Alzheimer's disease clinical trials: methods and placebo outcomes.
AB  - BACKGROUND: Eighteen-month-long randomized, placebo-controlled clinical trials
      are common for phase II and phase III drug development for Alzheimer's disease
      (AD). Yet, no 18-month trial has shown statistically significant outcomes
      favoring the test drug. We examined characteristics and underlying assumptions of
      these trials by assessing the placebo groups. METHODS: We searched the
      clinicaltrials.gov registry for randomized, placebo-controlled clinical trials
      for AD of at least 18-month duration and extracted demographic, clinical, and
      trials characteristics, and change in main outcomes from the placebo groups. We
      obtained additional information from presentations, abstracts, publications, and
      sponsors. RESULTS: Of 23 trials identified, 11 were completed and had baseline
      data available; nine had follow-up data available; 17 were phase III. General
      inclusion criteria were very similar except that minimum Mini-Mental State
      Examination (MMSE) scores varied from 12 to 20. Sample sizes ranged from 402 to
      1,684 for phase III trials and 80 to 400 for phase II. Cholinesterase inhibitor
      use was from 53% to 100%, and memantine use was from 13.5% to 78%. The AD
      Assessment Scale-cognitive (ADAS-cog) was the co-primary outcome in all trials;
      and activities of daily living, global severity, or global change ratings were
      the other co-primaries. APOE epsilon4 genotype carriers ranged from 58% to 67%;
      mean baseline ADAS-cog was 17.8 to 24.2. ADAS-cog worsening in the placebo groups
      during 18 months ranged from 4.34 to 9.10, with standard deviations from 8.17 to
      9.39, increasing during 18 months. CONCLUSIONS: Inclusion criteria are
      essentially similar to earlier 6-month and 12-month trials in which
      cholinesterase inhibitors were not allowed, as were mean ADAS-cog rates of
      change. Yet increasing variability and relatively little change overall in the
      ADAS-cog placebo groups, eg, about 25% of patients do not worsen by more than 1
      point, might make it more unlikely than previously assumed that a modestly
      effective drug can be reliably recognized, especially when the drug might work
      only to attenuate decline in function and not to improve function. These
      observations would be strengthened by pooling individual trials data, and
      pharmaceutical sponsors should participate in such efforts.

PMID- 19751919
TI  - Association of C-reactive protein with mild cognitive impairment.
AB  - BACKGROUND: Inflammation is proposed to play a role in the development of
      Alzheimer's disease, and may also be involved in the pathogenesis of mild
      cognitive impairment (MCI). This study examined the association of inflammatory
      markers in serum or plasma with prevalent MCI and MCI subtypes in a population
      based sample. METHODS: Olmsted County, MN, residents aged 70-89 years on October
      1, 2004, were evaluated using the Clinical Dementia Rating Scale, a neurological
      evaluation, and neuropsychological testing. Information ascertained for each
      participant was reviewed by an expert panel of neuropsychologists, physicians,
      and nurses, and a diagnosis of normal cognition, MCI, or dementia was made by
      consensus. C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis alpha
      (TNFalpha), and adiponectin were measured at baseline. RESULTS: Among 313
      subjects with MCI and 1570 cognitively normal subjects, a CRP level in the upper
      quartile (>3.3 mg/L) was significantly associated with MCI (odds ratio [OR],
      1.42; 95% confidence interval [CI], 1.00-2.01) and with nonamnestic MCI (OR,
      2.05; 95% CI, 1.12-3.78) after adjusting for age, sex, and years of education.
      However, there was no association with amnestic MCI (OR, 1.21; 95% CI, 0.81
      1.82). No association was observed with the other inflammatory markers.
      CONCLUSIONS: Plasma CRP is associated with prevalent MCI and with nonamnestic MCI
      in elderly, nondemented persons in a population-based setting. These findings
      suggest the involvement of inflammation in the pathogenesis of MCI.

PMID- 19751920
TI  - Defining and labeling disease-modifying treatments for Alzheimer's disease.
AB  - Alzheimer's disease (AD) might be treated with symptomatic, neuroprotective, or
      neurorestorative therapies. Neuroprotective and neurorestorative interventions
      are disease-modifying therapies. Disease modification can be defined as
      treatments or interventions that affect the underlying pathophysiology of the
      disease and have a beneficial outcome on the course of AD. In a clinical trial
      the criteria for affecting the underlying cause of the disease can be supported
      by demonstrating an effect on a biomarker such as medial temporal atrophy on
      magnetic resonance imaging (MRI) or diminished tau or phospho-tau levels in
      cerebrospinal fluid. The claim for a beneficial effect on the clinical course of
      AD is supported by a drug-placebo difference on the primary clinical outcomes of
      the clinical trial. A statistically significant correlation between the biomarker
      outcome and the clinical trial outcome would support the claim that these are
      based on the same underlying mechanism. Delayed start or staggered withdrawal
      designs might in themselves support a disease-modifying claim but are difficult
      to implement. A combination of clinical outcomes and biomarker measures is a more
      likely pathway to a disease-modifying claim. Labeling of disease-modifying agents
      might refer to slowing of disease progression, delay in reaching predefined
      disease milestones, or reduction in progression of a biomarker such as cerebral
      atrophy or ventricular enlargement on MRI. Prevention claims will depend heavily
      on biomarker outcomes.

PMID- 19751921
TI  - Reducing dangerous nighttime events in persons with dementia by using a nighttime
      monitoring system.
AB  - BACKGROUND: Nighttime activity, a common occurrence in persons with dementia,
      increases the risk for injury and unattended home exits and impairs the sleep
      patterns of caregivers. Technology is needed that will alert caregivers of
      nighttime activity in persons with dementia to help prevent injuries and
      unattended exits. METHODS: As part of a product development grant, a controlled
      pilot study was conducted to test the effectiveness of a new night monitoring
      system designed for informal caregivers to use in the home. Data from 53 subjects
      were collected at nine points in time during a 12-month period regarding injuries
      and unattended home exits that occurred while the caregiver slept. Nighttime
      activity frequently resulted in nursing home placement. RESULTS: The night
      monitoring system proved a reliable adjunct to assist caregivers in managing
      nighttime activity. A total of nine events (injuries or unattended home exits)
      occurred during the study, with 6 events occurring in the control group. With
      intent-to-treat analysis, there was no difference between the groups. However, in
      a secondary analysis that was based on use of the intervention, experimental
      subjects were 85% less likely to sustain an event than control subjects.
      CONCLUSIONS: When nighttime activity occurred, it resulted in severe injuries
      sometimes associated with subsequent nursing home placement. The night monitoring
      system represents a new technology that caregivers can use to assist them in
      preventing nighttime injuries and unattended home exits in care recipients with
      dementia.

PMID- 19751922
TI  - Alzheimer's disease drug development and the problem of the blood-brain barrier.
AB  - Alzheimer's disease (AD) drug development is limited by the presence of the blood
      brain barrier (BBB). More than 98% of all small-molecule drugs, and approximately
      100% of all large-molecule drugs, do not cross the BBB. Although the vast
      majority of AD drug candidates do not cross the BBB, the present-day AD drug
      development effort is characterized by an imbalance wherein >99% of the drug
      development effort is devoted to central nervous system (CNS) drug discovery, and
      <1% of drug development is devoted to CNS drug delivery. Future AD drug
      development needs a concerted effort to incorporate BBB sciences early in the CNS
      drug discovery process. This goal can be achieved by a reallocation of resources,
      and an expansion of research efforts in the pure science of BBB biology and the
      applied science of brain drug-targeting technology.

PMID- 19751923
TI  - Commentary on "Alzheimer's Disease Drug Development and the Problem of the Blood
      Brain Barrier".
AB  - The perspective by Dr. William Pardridge entitled "Alzheimer's Disease Drug
      Discovery and the Problem of the Blood-Brain Barrier" makes a strong case for the
      imbalance in resource distribution to the drug-discovery and brain drug delivery
      processes, where the latter received less than 1% of the investment of the
      former. My own calculations are consistent with this striking imbalance. Dr.
      Pardridge predicts that current trials of passive immunity against beta-amyloid
      peptide will likely fail, whereas past trials of active immunization exhibited
      trial-ending side effects, in part because of disruption of the integrity of the
      blood-brain barrier. To bring an assessment of the physiology of the blood-brain
      barrier and the brain delivery of drugs to the fore, several changes are needed
      in the way we perceive the problem, train our young scientists, organize research
      efforts, and incentivize reaching our common goals of effective drug therapy for
      Alzheimer's disease.

PMID- 19751924
TI  - Commentary on "Alzheimer's disease drug development and the problem of the blood
      brain barrier." The blood-brain barrier: a physical and conceptual challenge.

PMID- 19751925
TI  - Commentary on "Alzheimer's disease drug development and the problem of the blood
      brain barrier." Alzheimer's disease drugs: more than one barrier to breach.

PMID- 19751926
TI  - Computerized cognitive testing in aging.

PMID- 19751928
TI  - Maintaining focus in a world of distractions.

PMID- 19751929
TI  - Teaching excellence in nursing education: a caring framework.
AB  - Nursing education plays a central role in the ability to practice effectively. It
      follows that an optimally educated nursing workforce begets optimal patient care.
      A framework for excellence in nursing education could guide the development of
      novice educators, establish the basis for evaluating teaching excellence, and
      provide the impetus for research in this area. However, a review of the social
      sciences and nursing literature as well as a search for existing models for
      teaching excellence revealed an apparent dearth of evidence specific to
      excellence in nursing education. Therefore, we developed the Caring Framework for
      Excellence in Nursing Education. This framework evolved from a review of the
      generic constructs that exemplify teaching excellence: excellence in teaching
      practice, teaching scholarship, and teaching leadership. Nursing is grounded in
      the ethic of caring. Hence, caring establishes the foundation for this uniquely
      nursing framework. Because a teaching philosophy is intimately intertwined with
      one's nursing philosophy and the ethic of caring, it is also fundamental to the
      caring framework. Ideally, this framework will contribute to excellence in
      nursing education and as a consequence excellence in nursing practice and optimal
      patient care.

PMID- 19751930
TI  - Teaching excellence: what great teachers teach us.
AB  - Given the shortage of nurse educators, we sought to better understand teaching
      excellence because it is crucial for developing the next generation of nurses. A
      grounded theory approach was used. The sample included 17 respondents, thought to
      be excellent teachers, from universities across the United States. Consenting
      respondents were asked, "What do you do to bring nursing to life with your
      students?" Using line-by-line coding and the constant comparative method, five
      major themes emerged: (a) engagement, (b) relevance, (c) student centeredness,
      (d) facilitation of learning, and (e) dynamic process of becoming an excellent
      nursing educator. We found that the core category, engagement, included the
      faculty being (a) current and knowledgeable, (b) being clear in communication of
      objectives/outcomes, (c) being student centered, (d) being able to draw all
      students into active questioning and learning so that the process of discovery is
      enjoyable, and (e) using multiple strategies in teaching the content. The process
      of becoming an excellent teacher involved "change from 'instiller' to
      'facilitator' and laid the foundation for continued development of my teaching
      self." Those beginning to teach or seeking to improve their teaching may find the
      results enlightening.

PMID- 19751931
TI  - Use of aptitude to understand bachelor of science in nursing student attrition
      and readiness for the National Council Licensure Examination-Registered Nurse.
AB  - Attrition is a serious issue among Bachelor of Science in Nursing (BSN) students
      with attrition rates around 50% nationwide. To help minimize BSN student
      attrition, many nursing programs use commercially available standardized nursing
      aptitude tests as adjuncts to scholastic aptitude data, usually operationalized
      as pre-nursing grade point average, to select students for admission. Little is
      known regarding the usefulness of scholastic and nursing aptitude data for
      predicting long-term retention in a BSN program and readiness for the National
      Council Licensure Examination-Registered Nurse (NCLEX-RN). Therefore, the purpose
      of this study was to describe the relationships among scholastic aptitude,
      nursing aptitude, BSN student attrition prior to the final semester of the
      curriculum, and BSN student readiness for the NCLEX-RN. This study's findings,
      along with other findings in the literature, suggest the need for a parsimonious
      explanatory model of BSN student attrition that can be used to guide admission
      and progression policies, and ensure that students ready for the NCLEX-RN are the
      ones graduating from BSN programs.

PMID- 19751932
TI  - School for health sciences university students' opinions about male nurses.
AB  - This study was conducted after the new nursing law was passed in Turkey in May
      2007. According to the old nursing law in Turkey, only women could legally work
      as nurses. However, the new law made it possible for men to work as nurses as
      well. The researchers who conducted this study developed a survey for determining
      university nursing and midwifery students' opinions about the concept of a male
      nurse. No sampling method was used in this research, and the survey was
      administered to all students who came to school on the dates it was administered
      and agreed to participate voluntarily. A total of 331 students (88.7%) were
      administered the survey personally by the researchers. Of the participants in the
      study, 53.5% were in nursing and 46.5% were in midwifery schools. The majority
      (82.2%) of the students thought that nursing should be done by both genders,
      74.0% thought that having male members of the profession would have a part in the
      advancement of the profession, 72.8% thought that male nurses should be admitted
      to schools, 61.3% thought that male nurses could give care to male and female
      patients, and 80.7% thought that they could work in harmony with male and female
      nurses. In general, the students at our university have a positive attitude
      toward male nurses.

PMID- 19751933
TI  - Professional ethics: beyond the clinical competency.
AB  - Assessment of clinical competency in professional roles especially in crucial
      situations can improve the nursing profession. This qualitative research was
      conducted to determine the process of acquiring clinical competency by nurses in
      its cultural context and within the health care delivery system in Iran. This
      study, using grounded theory methodology, took place in universities and
      hospitals in Tehran. Nurses (36) included nurse managers, tutors, practitioners,
      and members of the Iranian Nursing Organization. Simultaneous data collection and
      analysis took place using participant semistructured interviews. Three categories
      emerged: (a) personal characteristics such as philanthropy, strong conscience,
      being attentive, accepting responsibility, being committed to and respecting self
      and others; (b) care environment including appropriate management systems, in
      service training provision, employment laws, and control mechanisms, suitable and
      adequate equipment; and (c) provision of productive work practices including love
      of the profession, critical thinking, nursing knowledge, and professional
      expertise. Professional ethics has emerged as the core variable that embodies
      concepts such as commitment, responsibility, and accountability. Professional
      ethics guarantees clinical competency and leads to the application of specialized
      knowledge and skill by nurses. The results can be used to form the basis of
      guiding the process of acquiring clinical competency by nurses using a systematic
      process.

PMID- 19751934
TI  - Ready for the World: preparing nursing students for tomorrow.
AB  - In 2004, a 5-year plan of international and intercultural education was developed
      by the University of Tennessee, Knoxville (UTK) to help students become ready for
      the changing world in which they will live. This program is called "Ready for the
      World." The University of Tennessee College of Nursing in Knoxville has
      integrated many of the suggestions from this program into the undergraduate
      nursing curriculum to prepare students for the world by making the world their
      classroom. Intercultural learning includes both a solid base of knowledge
      obtained in the classroom and multiple experiences that involve cultural
      interaction. Experiences begin on UTK's diverse campus and expand to the
      surrounding city of Knoxville, including interactions with vulnerable populations
      such as the homeless or elderly persons, then to nearby Appalachian communities,
      and on to Central America. Many of these experiences are offered for credit in
      the Community Health Nursing or the Transcultural Nursing courses. The knowledge
      nursing students acquire and their varied experiences will help them gain
      cultural competence for their future nursing practice.

PMID- 19751935
TI  - Bullying of staff registered nurses in the workplace: a preliminary study for
      developing personal and organizational strategies for the transformation of
      hostile to healthy workplace environments.
AB  - The primary purpose of this study was to validate the perceptions of frequency
      and patterns of bullying behavior experienced by registered nurses (RNs) across
      the United States. This study was completed to develop relevant and sensitive
      tailored interventions for the future. A 30-item anonymous electronic survey was
      used to identify the frequency, type, perpetrators, and personal and professional
      consequences of bullying. Findings from the overall population of 303 RN
      respondents (mean age of 49 years) indicated that 70% of the bullying was
      reported by a predominant group of staff RNs (n = 212), and it is this group that
      is the focus of this report. Of this group, bullying occurred (a) most frequently
      in medical-surgical (23%), critical care (18%), emergency (12%), operating
      room/Post Anesthesia Care Unit (9%), and obstetrical (7%) areas of care and (b)
      within the 5 years or less of employment on a unit (57%). Perpetrators included
      senior nurses (24%), charge nurses (17%), nurse managers (14%), and physicians
      (8%) who publicly humiliated, isolated, excluded, or excessively criticized the
      staff nurses. Subsequent stress levels were reported as moderate or severe, with
      support found primarily with family, colleagues, and friends and not with an
      available workplace infrastructure of solution. Many left the workplace
      completely with or without jobs awaiting them. Bullying among U.S. nurses is a
      hidden problem with significant patient-directed quality performance and
      workforce implications. It is critical that innovative strategies be developed
      and implemented to address the root cause of this problem.

PMID- 19751936
TI  - Hong Kong baccalaureate nursing students' stress and their coping strategies in
      clinical practice.
AB  - This study examined Hong Kong baccalaureate nursing students' stress and their
      coping strategies in clinical practice. Two hundred five nursing students
      completed a self-administrative survey including demographics, Perceived Stress
      Scale, and Coping Behavior Inventory. Results showed that students perceived a
      moderate level of stress (M = 2.10, SD =0.44). The most common stressor was lack
      of professional knowledge and skills. Among the four types of coping strategies
      (transference, stay optimistic, problem solving, and avoidance), transference was
      the most frequently used. Furthermore, senior students who perceived a higher
      level of stress from taking care of patients were more likely to choose problem
      solving strategies. Senior students who had no religious belief and perceived a
      higher level of stress from teachers and nursing staff were more likely to use
      avoidance strategies. The results provided valuable information for clinical
      educators in identifying students' needs, facilitating their learning in the
      clinical setting, and developing effective interventions to reduce stress.

PMID- 19751937
TI  - Perception in action: the impact of sensory information on sensorimotor
      synchronization in musicians and non-musicians.
AB  - The present study aimed at investigating to what extent sensorimotor
      synchronization is related to (i) musical specialization, (ii) perceptual
      discrimination, and (iii) the movement's trajectory. To this end, musicians with
      different musical expertise (drummers, professional pianists, amateur pianists,
      singers, and non-musicians) performed an auditory and visual synchronization and
      a cross-modal temporal discrimination task. During auditory synchronization
      drummers performed less variably than amateur pianists, singers and non
      musicians. In the cross-modal discrimination task drummers showed superior
      discrimination abilities which were correlated with synchronization variability
      as well as with the trajectory. These data suggest that (i) the type of
      specialized musical instrument affects synchronization abilities and (ii)
      synchronization accuracy is related to perceptual discrimination abilities as
      well as to (iii) the movement's trajectory. Since particularly synchronization
      variability was affected by musical expertise, the present data imply that the
      type of instrument improves accuracy of timekeeping mechanisms.

PMID- 19751938
TI  - The use of dielectric spectroscopy for the characterisation of the precipitation
      of hydrophobically modified poly(acrylic-acid) with divalent barium ions.
AB  - The use of dielectric spectroscopy as a monitor for coagulation processes was
      investigated. Hydrophobically modified poly(acrylic-acid) polymers were used as
      model macromolecules and coagulated with barium ions. The coagulation process was
      quantified using a photometric dispersion analyser, thereby serving as a point of
      reference for the dielectric spectroscopy. It was found that the hydrophobic
      modification increased the dosage of barium needed to obtain complete
      coagulation, whereas the dosage required to initiate coagulation was lowered. The
      coagulation of the polymer samples caused the relaxation time of the measured
      dielectric dispersion to increase, and this parameter was found to be a good
      indicator of the formation of polymer aggregates. The magnitude of the dielectric
      dispersion decreased as a function of barium dosage, but when coagulation was
      initiated an increase was observed. The observed agreement between the onset of
      coagulation and the changes in the dielectric dispersion shows the potential use
      of dielectric spectroscopy for the characterisation of coagulation processes.

PMID- 19751939
TI  - Increased DHEA and DHEA-S plasma levels in patients with post-traumatic stress
      disorder and a history of childhood abuse.
AB  - Current findings about dehydroepiandrosterone (DHEA) and dehydroepiandrosterone
      sulphate (DHEA-S) in patients with post-traumatic stress disorder (PTSD) have
      been inconsistent. We investigated whether a history of severe childhood
      traumatisation affects these steroids in PTSD patients. Patients of 33 with
      chronic PTSD (15 with and 18 without sexual and/or severe physical abuse before
      age 12) were studied in a combined low dose dexamethasone/corticotropin-releasing
      hormone (CRH) test. Mean pre-CRH levels of both plasma DHEA and DHEA-S were
      significantly increased in the subgroup with childhood abuse, the respective
      ratios with plasma cortisol were significantly lower. In the entire population of
      PTSD patients significant amounts of the variation of these parameters could be
      explained by childhood trauma history. Further studies are needed to clarify the
      potential role of DHEA and DHEA-S as biomarkers for severe early adverse events
      in patients suffering from PTSD and in other stress-related disorders.

PMID- 19751940
TI  - Room tilt illusion in Parkinson's disease: loss of spatial reference frames?
AB  - Room tilt illusion, a misperception that the entire room is tilted, is a rare but
      nonspecific neurological symptom. We report a patient with Parkinson's disease
      who developed typical room tilt illusion. Single photon emission computed
      tomography demonstrated hypoperfusion of the posterior area of the right
      intraparietal sulcus, which is related to discriminating the surface orientation
      of three-dimensional objects. Therefore, it is possible that dysfunction of this
      region of the intraparietal sulcus may have disrupted the integration of spatial
      reference frames for internal representation of the surrounding space in our
      patient, and thus may have caused room tilt illusion.

PMID- 19751941
TI  - Primary leptomeningeal anaplastic oligodendroglioma with a 1p36-19q13 deletion:
      report of a unique case successfully treated with Temozolomide.
AB  - Primary leptomeningeal oligodendroglioma occurs very rarely and in only one
      patient a deletion of chromosome 1p has been reported. We describe a 60-year-old
      man with a prior history of an epileptic seizure three years earlier, who was
      referred because of depression and a rapid evolving cognitive impairment. Brain
      MRI showed a diffuse right parieto-occipital subarachnoid enhancing lesion
      without intra-axial extension. The diagnosis of an anaplastic oligodendroglioma
      (WHO grade 3) was made on pathological examination. Molecular analysis using the
      FISH technique revealed a combined deletion of chromosomes 1p36 and 19q13. A
      rapid progression of the lesion was shown on MRI with leptomeningeal spinal
      metastases. The patient was treated with Temozolomide (TMZ) 150 mg/m(2) for 5
      days every 4 weeks and showed a marked clinical recovery. Serial MRI disclosed a
      near complete regression of the lesions with no residual enhancement left after 6
      cycles of chemotherapy. At progression following 8 cycles of TMZ the patient
      underwent craniospinal radiotherapy with complete response of his disease. To our
      knowledge this is the first report of a patient with a primary leptomeningeal
      anaplastic oligodendroglioma with diffuse spinal seeding bearing a 1p36/19q13
      deletion. Our patient achieved a durable clinical and radiological remission
      following TMZ treatment. Molecular analysis with determination of chromosome
      1p/19q deletions should be performed in all cases of leptomeningeal gliomas to
      select those patients who might benefit from TMZ chemotherapy.

PMID- 19751942
TI  - Assessing marine debris in deep seafloor habitats off California.
AB  - Marine debris is a global concern that pollutes the world's oceans, including
      deep benthic habitats where little is known about the extent of the problem. We
      provide the first quantitative assessment of debris on the seafloor (20-365 m
      depth) in submarine canyons and the continental shelf off California, using the
      Delta submersible. Fishing activities were the most common contributors of
      debris. Highest densities occurred close to ports off central California and
      increased significantly over the 15-year study period. Recreational monofilament
      fishing line dominated this debris. Debris was less dense and more diverse off
      southern than central California. Plastic was the most abundant material and will
      likely persist for centuries. Disturbance to habitat and organisms was low, and
      debris was used as habitat by some fishes and macroinvertebrates. Future trends
      in human activities on land and at sea will determine the type and magnitude of
      debris that accumulates in deep water.

PMID- 19751943
TI  - Apolipoprotein E on hepatitis C virion facilitates infection through interaction
      with low-density lipoprotein receptor.
AB  - Hepatitis C virus (HCV) infection is a major cause of liver disease. HCV
      associates with host apolipoproteins and enters hepatocytes through complex
      processes involving some combination of CD81, claudin-1, occludin, and scavenger
      receptor BI. Here we show that infectious HCV resembles very low density
      lipoprotein (VLDL) and that entry involves co-receptor function of the low
      density lipoprotein receptor (LDL-R). Blocking experiments demonstrate that beta
      VLDL itself or anti-apolipoprotein E (apoE) antibody can block HCV entry.
      Knockdown of the LDL-R by treatment with 25-hydroxycholesterol or siRNA ablated
      ligand uptake and reduced HCV infection of cells, whereas infection was rescued
      upon cell ectopic LDL-R expression. Analyses of gradient-fractionated HCV
      demonstrate that apoE is associated with HCV virions exhibiting peak infectivity
      and dependence upon the LDL-R for cell entry. Our results define the LDL-R as a
      cooperative HCV co-receptor that supports viral entry and infectivity through
      interaction with apoE ligand present in an infectious HCV/lipoprotein complex
      comprising the virion. Disruption of HCV/LDL-R interactions by altering
      lipoprotein metabolism may therefore represent a focus for future therapy.

PMID- 19751944
TI  - Effects of super-powdered activated carbon pretreatment on coagulation and trans
      membrane pressure buildup during microfiltration.
AB  - As a pretreatment for membrane microfiltration (MF), the use of powdered
      activated carbon (PAC) with a particle size much smaller than that of
      conventional PAC (super-powdered PAC, or S-PAC) has been proposed to enhance the
      removal of dissolved substances. In this paper, another advantage of S-PAC as a
      pretreatment for MF is described: the use of S-PAC attenuates trans-membrane
      pressure increases during the filtration operation. The floc particles that
      formed during coagulation preceded by S-PAC pretreatment were larger and more
      porous than the floc particles formed during coagulation preceded by PAC
      pretreatment and those formed during coagulation without pretreatment. This
      result was due to increased particle-particle collision frequency and better
      removal of natural organic matter, which inhibits coagulation by consuming
      coagulant, before the coagulation reaction. The caked fouling layer that built up
      on the membrane surface was thus more permeable with S-PAC than with normal PAC.
      Both physically reversible and irreversible membrane foulings were reduced, and
      more stable filtration was accomplished with S-PAC pretreatment.

PMID- 19751945
TI  - A novel in vitro system for the determination of bioconcentration factors and the
      internal dose in zebrafish (Danio rerio) eggs.
AB  - In this study a novel in vitro approach for the determination of bioconcentration
      factors (BCF) and rate constants of lipophilic substances utilizing zebrafish
      (Danio rerio) eggs is presented. Zebrafish eggs were exposed in a static exposure
      regime towards a phenanthrene solution and concentration-time profiles of the
      exposure solutions were analyzed over time. The rate constants and the BCF were
      obtained from the concentration-time profile with the use of a least-square fit
      to a non-linear model. The determined BCF at steady-state (after 72h of exposure)
      for phenanthrene was estimated to be only about 1.5 times lower, than the
      respective BCF value reported in the literature. For uptake of solutes in
      zebrafish embryos, different transport processes are assumed as substances have
      to pass the chorion first and subsequently the membranes of the embryo. To
      investigate this, the period to steady-state concentration between zebrafish eggs
      and the ambient medium for phenanthrene under an agitated and non-agitated static
      exposure regime were compared. It was found, that this equilibrium was reached
      within a shorter time frame under agitation, resulting in higher rate constants.
      In addition to the determination of bioconcentration parameters, the internal
      phenanthrene dose in zebrafish eggs was determined by utilizing a biomimetic
      extraction method with water as transfer medium. Approximately 55% of the
      expected accumulated phenanthrene amount in zebrafish eggs could be re-extracted
      with a silicone rod extraction method. These results agree very well to what has
      been observed in abiotic systems. The scope of the proposed in vitro protocol to
      serve as an alternative for BCF determinations using established in vivo animal
      testing protocols with adult fish is discussed.

PMID- 19751946
TI  - Photolysis of difloxacin and sarafloxacin in aqueous systems.
AB  - The photodegradation of two fluoroquinolone veterinary antibiotics, difloxacin
      (DIF) and sarafloxacin (SARA) has been explored for the first time in aqueous
      systems. The study was performed to evaluate the influence of pH, inorganics,
      humic substances, and other additives. The drugs followed first-order degradation
      kinetics in matrix free aqueous medium with a rate constant 'k' value of 0.82 and
      0.26 h(-1) for DIF and SARA, respectively. Studies performed at various pH
      revealed that the photolysis rates dropped sharply at pH >7 for DIF, while SARA
      dissipated faster with increasing pH. Humic substances acted as light barriers by
      attenuating the light intensity, to retard the drug degradation process. However,
      rapid drug dissipation was observed in the presence of additives like acetone,
      hydrogen peroxide, and phosphates, while inorganics such as fluoride, nitrate,
      and sulfate did not influence the drug photodegradation. Studies on the
      photolysis of DIF and SARA in river water revealed that both the drugs degraded
      rapidly under conditions that were relevant to natural systems, following direct
      photolysis mechanism. It was observed that SARA was the primary photoproduct of
      DIF and showed relatively a higher persistence than DIF. The findings were also
      substantiated by the quantum yield (Phi(c)) calculations. The analytical
      measurements were carried out with LC-MS/MS.

PMID- 19751947
TI  - Enzyme activities during degradation of polycyclic aromatic hydrocarbons by white
      rot fungus Phanerochaete chrysosporium in soils.
AB  - The degradation of three polycyclic aromatic hydrocarbons (PAHs), phenanthrene,
      pyrene and benzo[a]pyrene in soils by Phanerochaete chrysosporium, and the enzyme
      activities of lignin peroxidase (LiP) and manganese peroxidase (MnP) produced
      during degradation, were analyzed. The results showed that the 19-d percentage
      degradation ranged from 72.77+/-1.39% to 25.50+/-3.41% for the three compounds,
      and the maximum LiP and MnP activities ranged from 0.16+/-0.005 to 0.05+/-0.002 U
      g(-1) and from 1.92+/-0.03 to 0.54+/-0.03 U g(-1), respectively. Degradation
      percentage and enzyme activities both exhibited inverse relationships with the
      octanol/water partition coefficient (K(ow)) of the compounds, indicating that LiP
      and MnP from P. chrysosporium may be the primary enzymes responsible for PAH
      degradation in soil. As the soil organic matter (SOM) content increased from 0.3%
      for Soil 1 to 19% for Soil 4, the 19-d degradation percentage of pyrene decreased
      from 66.20+/-2.72% to 32.42+/-1.05%, and correspondingly, the maximum of LiP and
      MnP activities increased from 0.05+/-0.002 to 1.78+/-0.15 U g(-1) and from 0.34+/
      0.03 to 1.78+/-0.15 U g(-1), respectively. Hence, it is plausible to conclude
      that the P. chrysosporium appeared to degrade not only the PAHs with small
      molecular size but also the macromolecular SOM. When SOM differences are large,
      as in this study, SOM has greater influence on enzyme activity than low-level
      exotic pollutants.

PMID- 19751948
TI  - Adverse health effects of lead exposure on children and exploration to internal
      lead indicator.
AB  - Our research on adverse effects of lead exposures on physical and neurobehavioral
      health of children aged 6-12years in 4 villages, labeled as K, M, L, and X, in
      rural China, was reported in this article. Lead in blood (PbB), urine (PbU),
      hairs (PbH), and nails (PbN) were measured by graphite furnace atomic absorption
      spectrometry. Abbreviated Symptom Questionnaire of Conner's instruments and
      Revised Raven's Standard Progressive Matrices were applied to evaluate childhood
      attention deficit/hyperactivity disorders (ADHD) and intelligences. Geometric
      means (SD) of PbB, PbU, PbH and PbN concentrations were 71.2 microg/L (1.56),
      11.7 microg/g (1.75), 12.5 microg/g (2.82), and 25.3 microg/g (2.79),
      respectively. 54 (17.0%) children had PbB levels of > or =100 microg/L. Boys, 6
      10 years old, and living in village K were 2.11, 2.48, and 9.16 times,
      respectively, more likely to be poisoned by lead than girls, aged 11-12 years,
      and residing in X. 18 (5.7%) and 37 (11.7%) subjects had ADHD and mental
      retardations, respectively. Inverse relationships between intelligences and
      natural log transformed PbU and PbH levels were observed with respective odds
      ratios (95%CI) of 1.79 (1.00-3.22) and 1.46 (1.06-2.03) or 1.28 (1.04-1.58) and
      1.73 (1.18-2.52) by binary or ordinal logistic regression modeling. ADHD
      prevalence was different by gender and age of subjects. PbU, PbH, and PbN related
      to PbB positively with respective correlation coefficients of 0.530, 0.477, and
      0.181. Receiver operating characteristic (ROC) curves of the three measurements
      revealed areas under curves (AUCs) being 0.829, 0.758, and 0.687, respectively.
      In conclusion, children had moderate levels of lead exposures in this rural area.
      Intelligence declines were associated with internal lead levels among children.
      ROC analysis suggests PbU an internal lead indicator close to PbB.

PMID- 19751949
TI  - Nanocrystalline hydroxyapatite with simultaneous enhancements in hardness and
      toughness.
AB  - Using a series of dense hydroxyapatite (HA) bodies with well controlled grain
      sizes ranging from sub-micrometers to nanometers, we show that simultaneous
      improvements in hardness and toughness can be attained for nanocrystalline (nc)
      HA. It is demonstrated that the hardness of HA follows the Hall-Petch
      relationship as the grain size decreases from sub-micrometers to nanometers. In
      the same grain size range, the toughness of HA increases by as much as 74%
      because of the enhanced crack deflection associated with a transition from
      transgranular to intergranular cracking, promoted by the reduced grain size in
      the nanoscale. The mechanisms for simultaneous enhancements in the hardness and
      toughness of nc HA are discussed. It is anticipated that the principle of
      simultaneous improvements in hardness and toughness discovered in this study is
      also applicable to other nc ceramics, particularly non-cubic ceramics, with
      anisotropic elastic and thermal expansion properties.

PMID- 19751950
TI  - Volumetric interpretation of protein adsorption: kinetics of protein-adsorption
      competition from binary solution.
AB  - The standard solution-depletion method is implemented with SDS-gel
      electrophoresis as a multiplexing, separation-and-quantification tool to measure
      competition between two proteins (i and j) for adsorption to the same hydrophobic
      adsorbent particles (either octyl sepharose or silanized glass) immersed in
      binary-protein solutions. Adsorption kinetics reveals an unanticipated slow
      protein-size-dependent competition that controls steady-state adsorption
      selectivity. Two sequential pseudo-steady-state adsorption regimes (State 1 and
      State 2) are frequently observed depending on i, j solution concentrations. State
      1 and State 2 are connected by a smooth transition, giving rise to sigmoidally
      shaped adsorption-kinetic profiles with a downward inflection near 60 min of
      solution/adsorbent contact. Mass ratio of adsorbed i, j proteins (m(i)/m(j))
      remains nearly constant between States 1 and 2, even though both m(i) and m(j)
      decrease in the transition between states. State 2 is shown to be stable for 24 h
      of continuous-adsorbent contact with stagnant solution whereas State 2 is
      eliminated by continuous mixing of adsorbent with solution. In sharp contrast to
      binary-competition results, adsorption to hydrophobic adsorbent particles from
      single-protein solutions (pure i or j) exhibits no detectable kinetics within the
      timeframe of experiment from either stagnant or continuously mixed solution,
      quickly achieving a single steady-state value in proportion to solution
      concentration. Comparison of binary competition between dissimilarly-sized
      protein pairs chosen to span a broad molecular-weight (MW) range demonstrates
      that selectivity between i and j scales with MW ratio that is proportional to
      protein-volume ratio (ubiquitin, Ub, MW=10.7 kDa; human serum albumin, HSA,
      MW=66.3 kDa; prothrombin, FII, 72 kDa; immunoglobulin G, IgG, MW=160 kDa;
      fibrinogen, Fib, MW=341 kDa). Results are interpreted in terms of a kinetic model
      of adsorption that has protein molecules rapidly diffusing into an inflating
      interphase that is spontaneously formed by bringing a protein solution into
      contact with a physical surface (State 1). State 2 follows by rearrangement of
      proteins within this interphase to achieve the maximum interphase concentration
      (dictated by energetics of interphase dehydration) within the thinnest (lowest
      volume) interphase possible by ejection of interphase water and initially
      adsorbed proteins. Implications for understanding biocompatibility are discussed
      using a computational example relevant to the problem of blood-plasma
      coagulation.

PMID- 19751951
TI  - Long-term outcome of peripartum cardiomyopathy in a population with high
      seropositivity for human immunodeficiency virus.
AB  - BACKGROUND: Peripartum cardiomyopathy (PPCM) is a rare cardiomyopathy with a high
      risk of mortality. The present study assessed clinical outcome and mortality over
      a 2-year period in an African cohort of 80 PPCM patients. METHODS: A prospective
      study over a 2-year period at a tertiary center, where 80 consecutive women
      presenting with PPCM were enrolled on first diagnosis. Patients obtained standard
      heart failure therapy. Detailed assessments included echocardiography, NYHA
      functional class, left ventricular ejection fraction (LVEF), mortality and serum
      levels for hemoglobin, CRP, IL-6, TNF-alpha, Fas/Apo-1, and T-cell count at each
      6-month intervals for 24 months. RESULTS: Baseline mean age was 30 +/- 7 years;
      38% were primigravidas and 34% were co-infected with HIV. NYHA functional class
      III-IV was present in 89% patients with a mean LVEF of 30 +/- 9%. Four patients
      were lost to follow-up, 9 moved to remote areas, 7 were excluded due to
      subsequent pregnancy. The 2-year mortality rate was 28%. Eight of 80 (10%) died
      by 6 months. Mean LVEF of surviving patients was: 44 +/- 11% at 6-months, 46 +/-
      13% at 12-months and 50 +/- 14% at 24-months follow-up. Of the 69 patients still
      enrolled at 6 months 14 (20%) died over the remaining 18-month period, despite
      functional recovery. No statistically significant difference in LVEF and
      mortality was observed between PPCM patients with or without HIV co-infection.
      CONCLUSION: The novel finding of this study is the continuous high mortality of
      PPCM patients occurring beyond 6 months independent of HIV infection and
      subsequent pregnancy. This finding strongly encourages the need for long-term
      clinical follow-up and management of women with PPCM.

PMID- 19751952
TI  - Crossing of a calcified "balloon uncrossable" coronary chronic total occlusion
      facilitated by a laser catheter: a case report and review recent four years'
      experience at the Thoraxcenter.
AB  - Failure to cross with a balloon is a well recognised cause of failure to
      recanalise a chronic total occlusion (CTO) despite successfully positioning a
      guidewire into the distal true lumen. One technique that is infrequently used
      currently is excimer laser assisted coronary intervention. We report a patient
      with CTO in whom in the fourth attempt, the operators succeeded by using a laser
      catheter. Also, we review the cases treated with laser catheter in our
      institution during these recent 4 years. The laser catheter can be useful in
      selected patients including those with CTO where a balloon would not pass despite
      a guidewire in the distal true lumen.

PMID- 19751953
TI  - Intra-coronary administration of cyclosporine limits infarct size, attenuates
      remodeling and preserves left ventricular function in porcine acute anterior
      infarction.
AB  - BACKGROUND: We tested whether intra-coronary administration of cyclosporine
      effectively preserves left ventricular (LV) function in porcine acute anterior
      wall infarction (AMI). METHODS AND RESULTS: Eighteen male mini-pigs were
      randomized into groups 1 (control), 2 (AMI alone), and 3 (AMI with cyclosporine
      treatment). AMI was induced by ligating middle left anterior descending artery
      (LAD). Fifteen minutes after ligation, saline and cyclosporine (2.5 mg)
      combination was injected into LAD beyond ligation in groups 2 and 3,
      respectively. Echocardiography was performed after 14 days, followed by animal
      sacrifice. Larger infarcted area (IA) was noted in group 2 than in group 3 (p <
      0.001). In both IA and peri-IA, mRNA expressions of IL-8, MMP-9, caspase 3 and
      Bax were higher, whereas PGC-1alpha, eNOS and Bcl-2 were lower in group 2 than in
      groups 1 and 3 (p < 0.01). The mRNA expression of IL-10 was upregulated in both
      IA and peri-IA in group 3 compared with groups 1 and 2. Apoptotic nuclei and CD40
      positive cells were higher in both peri-IA and non-IA in group 2 than in groups 1
      and 3 (p < 0.001). Oxidative stress and cytosolic cytochrome C in IA were
      increased in group 2 than in groups 1 and 3 (p < 0.001). Mid-LV end-systolic
      areas were higher, whereas mid-LV wall fractional area change was lower in group
      2 than in groups 1 and 3 (p < 0.001). CONCLUSIONS: Intra-coronary administration
      of cyclosporine effectively limits infarct size, attenuates LV remodeling and
      preserves LV function.

PMID- 19751954
TI  - Growth of Lactobacillus paracasei A13 in Argentinian probiotic cheese and its
      impact on the characteristics of the product.
AB  - The growth capacity of probiotic Lactobacillus paracasei A13, Bifidobacterium
      bifidum A1 and L. acidophilus A3 in a probiotic fresh cheese commercialized in
      Argentina since 1999 was studied during its manufacture and refrigerated storage
      at 5 degrees C and 12 degrees C for 60 days. Additionally, viable cell counts for
      probiotic bacteria in the commercial product are reported for batch productions
      over the last 9 years. L. paracasei A13 grew a half log order at 43 degrees C
      during the manufacturing process of probiotic cheese and another half log order
      during the first 15 days of storage at 5 degrees C, without negative effects on
      sensorial properties of the product. However, a negative impact on sensorial
      characteristics was observed when cheeses were stored at 12 degrees C for 60
      days. Colony counts in the commercial product showed variations from batch to
      batch over the last 9 years. However, colony counts for each probiotic bacterium
      were always above the minimum suggested. Growth capacity of L. paracasei A13 in
      cheese during manufacturing and storage, mainly at temperatures commonly found in
      retail display cabinets in supermarkets (12 degrees C or more), would make it
      necessary to re-evaluate its role as possible probiotic starter and the
      consequences on food sensorial characteristics if storage temperature during
      commercial shelf life is not tightly controlled.

PMID- 19751955
TI  - Wristwatch use and hospital-acquired infection.
AB  - The wrists and hands of hospital-based healthcare workers (HCWs) were sampled for
      bacterial contamination in two consecutive cross-sectional cohort studies of
      wristwatch wearers and non-wristwatch wearers. In the first study (N=100), wrists
      were sampled by skin swabs and hands by direct plate inoculation. In the second
      study (N=155) wrists were sampled after each HCW removed the watch immediately
      prior to sampling. Staphylococcus aureus was found on the hands of 25% of
      wristwatch wearers and 22.9% of non-wristwatch wearers in the first study. Watch
      wearers had higher counts of bacteria on their wrist (P<0.001) but not on their
      hands. In the second study, removal of the watch prior to sampling resulted in
      increased counts of bacteria on both hands as well as on the watch wrist compared
      with non-watch wearers (P<0.001). In conclusion, wearing a wristwatch results in
      an increase in bacterial contamination of the wrist but excess hand contamination
      does not occur unless the watch is manipulated.

PMID- 19751956
TI  - ISB Clinical Biomechanics Award 2009: toe weakness and deformity increase the
      risk of falls in older people.
AB  - BACKGROUND: Hallux valgus and lesser toe deformities are highly prevalent foot
      problems in older people. One factor contributing to the development of these toe
      deformities is reduced toe flexor strength. As adequate toe flexor strength is
      also crucial in maintaining balance, it was hypothesised that poor toe flexor
      strength and toe deformities would increase the risk of falls in community
      dwelling older people. METHOD: The feet of 312 men and women aged 60-90 years
      were assessed for the presence of lesser toe deformities and hallux valgus.
      Hallux and lesser toe flexor strength were assessed using an emed AT-4 pressure
      platform and novel test protocol. Participants were then followed prospectively
      to determine their falls incidence over 12 months. FINDINGS: During the 12 month
      follow-up, 107 (35%) participants experienced a fall. Compared to non-fallers,
      fallers displayed significantly less strength of the hallux (11.6 (SD 6.9) versus
      14.8 (SD 7.8)% BW, P<0.01) and lesser toes (8.7 (SD 4.7) versus 10.8 (SD 4.5)%
      BW, P<0.01), and were more likely to have hallux valgus (relative risk [RR]=2.36;
      95% CI=1.03-5.45; P<0.01) and lesser toe deformity (RR=1.32; 95% CI=1.04-1.69;
      P<0.01). INTERPRETATION: Reduced toe flexor strength and the presence of toe
      deformities increase the risk of falling in older people. To reduce this risk,
      interventions designed to increase strength of the toe flexor muscles combined
      with treatment of those older individuals with toe deformities may be beneficial.

PMID- 19751957
TI  - Development of models for predicting toxicity from sediment chemistry by partial
      least squares-discriminant analysis and counter-propagation artificial neural
      networks.
AB  - There is strong interest in developing tools to link chemical concentrations of
      contaminants to the potential for observing sediment toxicity that can be used in
      initial screening-level sediment quality assessments. This paper presents new
      approaches for predicting toxicity in sediments, based on 10-day survival tests
      with marine amphipods, from sediment chemistry, by means of the application of
      Partial Least Squares-Discriminant Analysis (PLS-DA) and Counter-propagation
      Artificial Neural Networks (CP-ANNs) to large historical databases of chemical
      and toxicity data. The exploration of the internal structure of the developed
      models revealed inherent limitations of predicting toxicity from common chemical
      analyses of bulk contaminant concentrations. However, the results obtained in the
      validation of these models combined relevant values of non-error classification
      rate, sensitivity and specificity of, respectively, 76, 87 and 73% with PLS-DA
      and 92, 75 and 97% with CP-ANNs, outperforming the results reported for previous
      approaches.

PMID- 19751958
TI  - Interoceptive sensitivity in anxiety and anxiety disorders: an overview and
      integration of neurobiological findings.
AB  - Interoceptive sensitivity, particularly regarding heartbeat, has been suggested
      to play a pivotal role in the pathogenesis of anxiety and anxiety disorders. This
      review provides an overview of methods which are frequently used to assess
      heartbeat perception in clinical studies and summarizes presently available
      results referring to interoceptive sensitivity with respect to heartbeat in
      anxiety-related traits (anxiety sensitivity, state/trait anxiety), panic disorder
      and other anxiety disorders. In addition, recent neurobiological studies of
      neuronal activation correlates of heartbeat perception using positron emission
      tomography (PET), functional magnetic resonance imaging (fMRI) or
      electroencephalographic (EEG) techniques are presented. Finally, possible
      clinical and therapeutic implications (e.g., beta-blockers, biofeedback therapy,
      cognitive interventions and interoceptive exposure) of the effects of heartbeat
      perception on anxiety and the anxiety disorders and the potential use of
      interoceptive sensitivity as an intermediate phenotype of anxiety disorders in
      future neurobiological and genetic studies are discussed.

PMID- 19751959
TI  - City structure, obesity, and environmental justice: an integrated analysis of
      physical and social barriers to walkable streets and park access.
AB  - Local parks and walkable neighborhoods are commonly cited as elements of the
      urban environment that promote physical activity and reduce obesity risk. When
      those vulnerable to obesity-related diseases live in neighborhoods without these
      qualities, it works against environmental justice goals that aim for a fair
      distribution of amenities. We use geographic information systems (GIS) to
      evaluate the relationship between the distribution of populations vulnerable to
      obesity and proximity to parks and walkable street networks in Phoenix, Arizona,
      USA. Though previous studies have used GIS to assess the distribution of access
      to opportunities for physical activity, none have analyzed access to both parks
      and walkable resources at once. Neither have they included data that reflects
      findings on a smaller scale indicating that perceptions of resource quality,
      safety, and cultural relevance also affect physical activity levels. We include
      these safety and quality factors in our study through statistical data on traffic
      fatalities, crime rates and park size. We find that, counter to predictions,
      subpopulations generally considered vulnerable to obesity (and environmental
      injustices more generally) are more likely to live in walkable neighborhoods and
      have better walking access to neighborhood parks than other groups in Phoenix.
      However, crime is highest in walkable neighborhoods with large Latino/a and
      African-American populations and parks are smaller in areas populated by
      Latino/as. Given the higher prevalence of obesity and related diseases in lower
      income and minority populations in Phoenix, the results suggest that benefits of
      built environments may be offset by social characteristics. Our most consistent
      finding indicates a strong negative relationship between the percentage of the
      population under 18 years of age living in an area and the likelihood that the
      structure of the built environment supports physical activity. Children under 18
      are significantly underrepresented in regions deemed highly walkable and those
      with access to parks.

PMID- 19751960
TI  - Linguistic correlates of asymmetric motor symptom severity in Parkinson's
      Disease.
AB  - Asymmetric motor severity is common in Parkinson's Disease (PD) and provides a
      method for examining the neurobiologic mechanisms underlying cognitive and
      linguistic deficits associated with the disorder. In the present research, PD
      participants (N=31) were assessed in terms of the asymmetry of their motor
      symptoms. Interviews with the participants were analyzed with the Linguistic
      Inquiry and Word Count (LIWC) program. Three measures of linguistic complexity -
      the proportion of verbs, proportion of function words, and sentence length - were
      found to be affected by symptom asymmetry. Greater left-side motor severity (and
      hence greater right-hemisphere dysfunction) was associated with the production of
      significantly fewer verbs, function words, and shorter sentences. Hence, the
      production of linguistic complexity in a natural language context was associated
      with relatively greater right hemisphere involvement. The potential
      neurobiological mechanisms underlying this effect are discussed.

PMID- 19751961
TI  - Autonomic impairment in borderline personality disorder: a laboratory
      investigation.
AB  - Recent research suggests that emotional dysfunction in psychiatric disorders can
      be reflected in autonomic abnormalities. The present study examines sympathetic
      and parasympathetic autonomic nervous system activity in individuals with
      Borderline Personality Disorder (BPD) before, during, and following a social
      stressor task. Data were obtained from an analogue sample of participants
      screening positive for BPD (n=12) and healthy controls (n=28). In general, BPD
      participants exhibited increased sympathetic activity (indexed by Cardiac
      Sympathetic Index, CSI; Toichi et al., 1997) and decreased parasympathetic
      activity (indexed by Respiratory Sinus Arrhythmia, RSA) compared to controls.
      During the stressful task, BPD and control participants exhibited different
      trajectories of sympathetic activation: estimates of sympathetic activity
      increased for BPD participants and decreased for controls. Furthermore, BPD
      participants reported the task (but not baseline or recovery phases) to be more
      frustrating than controls. Findings are interpreted in the context of Polyvagal
      theory.

PMID- 19751962
TI  - Mechanisms of deficit of visuospatial attention shift in children with
      developmental coordination disorder: a neurophysiological measure of the
      endogenous Posner paradigm.
AB  - The purpose of this study was to investigate and compare the mechanisms of brain
      activity, as revealed by a combination of the visuospatial attention shifting
      paradigm and event-related potentials (ERP) in children with developmental
      coordination disorder (DCD) and typically developing children. Twenty-eight DCD
      children and 26 typically developing children were recorded with regard to their
      behavioral performance and ERP measures during a variant of the endogenous Posner
      paradigm, in which they should react to visual targets preceded by spatial cues
      or presented uncued. Children with DCD showed longer reaction time and a deficit
      in inhibitory response capacity when compared to typically developing children.
      The electrophysiological characteristics also showed distinct modulatory effects
      upon attentional orienting, anticipatory mechanisms, and cognitive-to-motor
      transfer in children with DCD: longer cue-P3 and target-N1 latency, smaller
      target-P3 amplitude, an elongated interval between N2 and the motor response (N2
      RT), and small areas on contingent negative variation (CNV). The combined
      analysis of behavioral performance and ERP data suggested that children with DCD
      had deficits of slower target identification (N1), less ability in
      interhemispheric (P3) and cognitive-to-motor transfer speed (N2-RT), as well as a
      less mature anticipatory and executive process (CNV).

PMID- 19751963
TI  - Curcumin inhibits nuclear localization of telomerase by dissociating the Hsp90 co
      chaperone p23 from hTERT.
AB  - The molecular chaperone complex Hsp90-p23 interacts with the rate-limiting
      catalytic subunit of telomerase, hTERT. Although their interactions are required
      for proper folding of nascent hTERT as well as the assembly of active telomerase,
      the precise role of the chaperone proteins in regulation of nuclear localization
      of hTERT remains unclear. Here we demonstrate that curcumin inhibits telomerase
      activity in a time- and dose-dependent manner by decreasing the level of hTERT
      expression. Following curcumin treatment, we observed a clear accumulation of
      hTERT in the cytoplasmic compartment of the cell. The curcumin-induced
      cytoplasmic retention of hTERT could be due to failure of nuclear import, and the
      resulting cytoplasmic hTERT protein was rapidly ubiquitinated and degraded by the
      proteasome. We also report that curcumin treatment results in a substantial
      decrease in association of p23 and hTERT but does not affect the Hsp90 binding to
      hTERT. In contrast, the treatment of the Hsp90 inhibitor geldanamycin promotes
      dissociation of both Hsp90 and p23 proteins from hTERT. Taken together, these
      results demonstrate that the interaction of the Hsp90-p23 complex with hTERT is
      critical for regulation of the nuclear localization of telomerase, and that down
      regulation of hTERT by curcumin involves dissociating the binding of hTERT with
      p23. Thus, inhibition of nuclear translocation of hTERT by curcumin may provide
      new perspectives for regulation of telomerase activity during tumorigenic
      progression.

PMID- 19751964
TI  - Transforming growth factorbeta(1) transactivates EGFR via an H(2)O(2)-dependent
      mechanism in squamous carcinoma cell line.
AB  - TGFbeta is known to transactivate EGFR. However, the signaling component involved
      in this crosstalk has yet to be revealed. Here, we found that TGFbeta(1)
      phosphorylated EGFR in a dose-dependent manner in SCC13 and A431 cells, and it
      was not blocked by EGF-neutralizing antibody. H(2)O(2) was increased by
      TGFbeta(1) treatment in the same time-kinetics as EGFR activation. Pretreatment
      of N-acetyl cysteine abolished TGFbeta(1)-induced H(2)O(2) induction and EGFR
      activation. Direct treatment of H(2)O(2) phosphorylated EGFR and catalase
      inhibitor prolonged TGFbeta(1)-induced EGFR activation. These results show that
      TGFbeta(1) activates EGFR via an H(2)O(2)-dependent mechanism, which subsequently
      leads to the activation of Erk(1/2).

PMID- 19751965
TI  - Increase in tissue inhibitor of metalloproteinase-2 (TIMP-2) levels and
      inhibition of MMP-2 activity in a metastatic breast cancer cell line by an anti
      invasive small molecule SR13179.
AB  - Tissue inhibitor of metalloproteinase-2 (TIMP-2), the endogenous inhibitor of
      matrix metalloproteinase-2 (MMP-2), regulates tumor invasion by modulating the
      activity of MMP-2. In addition, TIMP-2 is involved in the direct regulation of
      cell growth and angiogenesis, independent of MMP inhibition. Therefore, the
      development of therapeutic agents that increase TIMP-2 levels may offer a novel
      and broad approach to anti-neoplastic therapy. We report that a novel small
      molecule synthetic flavanoid SR13179, which inhibits the invasion of a highly
      metastatic human breast cancer cell line MCF-10CA1a through Matrigel,
      significantly increases protein and mRNA levels of TIMP-2 in a time- and dose
      dependent manner. SR13179 inhibits the gelatinolytic activity of MMP-2 by >50%
      but has no effect on MMP-2 protein expression. SR13179 also possesses potent anti
      tumor activity in several tumor cell lines regardless of their hormone receptor,
      p53 or multi-drug resistance status. Given the multifunctional inhibitory
      activity of TIMP-2 on tumor growth and invasion, the observed increase in TIMP-2
      expression by SR13179 may play a central role in the anti-tumor and anti-invasive
      activity of this novel small molecule. Modulation of TIMP-2 protein expression
      may be a new molecular target for anti-metastatic adjuvant therapy for breast and
      other cancers.

PMID- 19751966
TI  - Dysphagia in head and neck cancer.
AB  - Dysphagia is an important symptom of head and neck cancer (HNC), as well as
      representing a significant complication of its treatment. The treatment of HNC
      can result in neuromuscular and sensory damage affecting any stage of the
      swallow. The protective mechanisms during swallowing afforded by the structures
      in the pharynx are also affected in HNC. This article reviews the effect of the
      various treatment modalities in HNC on the swallowing mechanism. Various
      interventions which may play in role in relieving this dysphagia are also
      discussed. Due stress has been laid on the need for a multi-disciplinary approach
      for an optimal outcome in rehabilitating a patient's swallow after treatment for
      HNC.

PMID- 19751967
TI  - The syndrome of perisylvian polymicrogyria with congenital arthrogryposis.
AB  - BACKGROUND: Bilateral perisylvian polymicrogyria (BPP) is a well-recognized
      malformation of cortical development commonly associated with epilepsy, cognitive
      impairment, and oromotor apraxia. Reports have suggested the association of BPP
      with arthrogryposis multiplex congenita. We sought to investigate the clinical,
      electrophysiological, and neuroradiological features of this combined syndrome to
      determine if there are unique features that distinguish BPP with arthrogryposis
      from BPP alone. METHODS: Cases of BPP with congenital arthrogryposis were
      identified from a large research database of individuals with polymicrogyria.
      Clinical features (including oromotor function, seizures, and joint
      contractures), MR brain imaging, and results of neuromuscular testing were
      reviewed. RESULTS: Ten cases of BPP with congenital arthrogryposis were
      identified. Most cases had some degree of oromotor apraxia. Only a few had
      seizures, but a majority of cases were still young children. Electrophysiological
      studies provided evidence for lower motor neuron or peripheral nervous system
      involvement. On brain imaging, bilateral polymicrogyria (PMG) centered along the
      Sylvian fissures was seen, with variable extension frontally or parietally; no
      other cortical malformations were present. We did not identify obvious
      neuroimaging features that distinguish this syndrome from that of BPP without
      arthrogryposis. CONCLUSIONS: The clinical and neuroimaging features of the
      syndrome of BPP with congenital arthrogryposis appear similar to those seen in
      cases of isolated BPP without joint contractures, but electrophysiological
      studies often demonstrate coexistent lower motor neuron or peripheral nervous
      system pathology. These findings suggest that BPP with arthrogryposis may have a
      genetic etiology with effects at two levels of the neuraxis.

PMID- 19751968
TI  - Abnormal cortisol levels during the day and cortisol awakening response in first
      episode psychosis: the role of stress and of antipsychotic treatment.
AB  - First-episode psychosis (FEP) patients show hyperactivity of the hypothalamic
      pituitary-adrenal (HPA) axis, but the mechanisms leading to this are still
      unclear. The aim of this study was to investigate the role of stress and
      antipsychotic treatment on diurnal cortisol levels, and on cortisol awakening
      response, in FEP. Recent stressful events, perceived stress and childhood trauma
      were collected in 50 FEP patients and 36 healthy controls using structured
      instruments. Salivary cortisol was obtained at awakening, at 15, 30, and 60min
      after awakening, and at 12 and 8pm. Patients experienced more recent stressful
      events, perceived stress and childhood trauma than controls (p<0.001). Patients
      had a trend for higher diurnal cortisol levels (p=0.055), with those with less
      than two weeks of antipsychotics showing significantly higher cortisol levels
      than both patients with more than two weeks of antipsychotics (p=0.005) and
      controls (p=0.002). Moreover, patients showed a blunted cortisol awakening
      response compared with controls, irrespectively of antipsychotic treatment
      (p=0.049). These abnormalities in patients were not driven by the excess of
      stressors: diurnal cortisol levels were negatively correlated with the number of
      recent stressful events (r=-0.36, p=0.014), and cortisol awakening response was
      positively correlated with a history of sexual childhood abuse (r=0.33, p=0.033).
      No significant correlations were found between perceived stress or severity of
      symptoms and cortisol levels, either diurnal or in the awakening response. Our
      study shows that antipsychotics normalize diurnal cortisol hyper-secretion but
      not the blunted cortisol awakening response in FEP; factors other than the excess
      of psychosocial stress explain HPA axis abnormalities in FEP.

PMID- 19751969
TI  - Triple-negative breast cancer and brain metastases.

PMID- 19751970
TI  - A continuous-flow biodiesel production process using a rotating packed bed.
AB  - The continuous-flow transesterification of soybean oil with methanol using a
      rotating packed bed (RPB) for the production of fatty acid methyl esters
      (biodiesel) is presented herein. The RPB, which provides high centrifugal force
      and has an adjustable rotational speed, is employed as a novel
      transesterification reactor. In this study, biodiesel is synthesized via the
      methanolysis of soybean oil using potassium hydroxide as the catalyst. The
      following variables were investigated for their effects on transesterification
      efficiency: the methanol-oil molar ratio, the estimated hydraulic retention time,
      the rotational speed of the packed-bed rotator, the reaction temperature, and the
      catalyst dosage. The yield of the fatty acid methyl esters (Y(FAME)) in the RPB
      system depends significantly on the experimental conditions, which influence the
      residence time distribution, the transesterification reaction rate, and the
      micromixing intensity. Due to its excellent micromixing characteristics, the RPB
      system shows satisfactory transesterification efficiency. The values of Y(FAME),
      productivity of FAMEs (P(FAME)), and P(FAME) per unit reactor volume
      (P(FAME)/V(R)) in the RPB are used to evaluate the performance for biodiesel
      production and allow for further comparison with other continuous
      transesterification reactors. Consequently, a RPB is considered a practical
      transesterification reactor with high transesterification efficiency.

PMID- 19751971
TI  - Treatment of linear alkylbenzene sulfonate in a horizontal anaerobic immobilized
      biomass reactor.
AB  - Linear alkylbenzene sulfonate (LAS) is an anionic surfactant widely used to
      manufacture detergents and found in domestic and industrial wastewater. LAS
      removal was evaluated in a horizontal anaerobic immobilized biomass reactor. The
      system was filled with polyurethane foam and inoculated with sludge that was
      withdrawn from an up flow anaerobic sludge blanket reactor that is used to treat
      swine wastewater. The reactor was fed with easily degradable substrates and a
      solution of commercial LAS for 313 days. The hydraulic retention time applied was
      12h. The system was initially operated without detergent and resulted to 94%
      reduction of demand. The mass balance in the system indicated that the LAS
      removal efficiency was 45% after 18 0days. From the 109 th day to the 254 th day,
      a removal efficiency of 32% was observed. The removal of LAS was approximately
      40% when 1500 mg of LAS were applied in the absence of co-substrates suggesting
      that the LAS molecules were used selectively. Microscopic analyses of the biofilm
      revealed diverse microbial morphologies and denaturing gradient gel
      electrophoresis profiling showed variations in the total bacteria and sulfate
      reducing bacteria populations. 16S rRNA sequencing and phylogenetic analyses
      demonstrated that members of the order Clostridiales were the major components of
      the bacterial community in the last step of the reactor operation.

PMID- 19751972
TI  - Biological treatment processes for fish processing wastewater--a review.
AB  - Water consumption in a fish-processing industry and high-strength wastewater from
      such an industry are of great concern world-wide. Liquid effluent regulations are
      becoming more stringent day by day. Biological treatment is the best option for
      such a wastewater. Anaerobic processes such as upflow anaerobic sludge blanket
      (UASB) reactor, anaerobic filter (AF) and anaerobic fluidized bed (AFB) reactor
      can achieve high (80-90%) organics removal and produce biogas. Aerobic processes
      such as activated sludge, rotating biological contactor, trickling filter and
      lagoons are also suitable for organics removal. Anaerobic digestion followed by
      an aerobic process is an optimal process option for fish processing wastewater
      treatment.

PMID- 19751973
TI  - Decolorization of Brilliant Scarlet GR enhanced by bioaugmentation and redox
      mediators under high-salt conditions.
AB  - The synergistic effects of bioaugmentation and redox mediator catalysis on
      Brilliant Scarlet GR decolorization under high-salt conditions were investigated.
      Two start-up models were tested in simulated anaerobic sequencing batch reactors
      (AnSBRs). The results showed that the start-up was shortened by bioaugmentation
      with salt-tolerant strain TL, and the biodecolorization was promoted by adding
      anthraquinone after acclimatization. The start-up time of non-bioaugmented and
      bioaugmented activated sludge systems were about 9 d and 5d, respectively. It was
      proved that anthraquinone could not enhance the process in the start-up stage
      because it would inhibit some potential azo-reducing microorganisms in the non
      acclimatized activated sludge. When anthraquinone was added to the acclimatized
      bioaugmented system, the maximal decolorization rate was 700-800 mg L(-1)d(-1).
      PCR-DGGE fingerprints demonstrated that both the diversity and pattern of
      microbial community were affected by the addition of bioaugmentation strain and
      anthraquinone. All the dominant bands were confirmed as anaerobic bacteria.

PMID- 19751974
TI  - Discovery of N-substituted pyridinones as potent and selective inhibitors of p38
      kinase.
AB  - The identification and evolution of a series of potent and selective p38
      inhibitors is described. p38 inhibitors based on a N-benzyl pyridinone high
      throughput screening hit were prepared and their SAR explored. Their design was
      guided by ligand bound co-crystals of p38alpha. These efforts resulted in the
      identification of 12r and 19 as orally active inhibitors of p38 with significant
      efficacy in both acute and chronic models of inflammation.

PMID- 19751975
TI  - The proteoglycan region of the tumor-associated carbonic anhydrase isoform IX
      acts as anintrinsic buffer optimizing CO2 hydration at acidic pH values
      characteristic of solid tumors.
AB  - The enzymatic activities of carbonic anhydrase (CA, EC 4.2.1.1) isozymes CA I,
      II, IX (catalytic domain (cdCA IX) and catalytic domain plus proteoglycan, flCA
      IX), XII and XIV were investigated as a function of pH for the CO2 hydration to
      bicarbonate and a proton. The cytosolic isoforms CA I and II as well as the
      catalytic domain of CA IX, together with the transmembrane isoforms CA XII and
      XIV showed sigmoid pH dependencies of k(cat)/KM, with a pKa of 6.90-7.10, showing
      thus optimal catalytic efficiency around pH 7. The full length CA IX had a
      similar shape of the pH dependency curve but with a pKa of 6.49, having thus
      maximal catalytic activity at pH values around 6.5, typical of hypoxic solid
      tumors in which CA IX is overexpressed. The proteoglycan domain of CA IX (present
      only in this transmembrane isoform) may thus act as an intrinsic buffer promoting
      efficient CO2 hydration at acidic pH values found in hypoxic tumors.

PMID- 19751976
TI  - Congenital monomelic muscular hypertrophy of the upper extremity.
AB  - Pathological muscular hypertrophy results from either muscular or neurogenic
      damage. Rarely, it is caused by a congenital malformation consisting of a
      unilateral muscular hyperplasia of the upper extremity. We report on a young
      woman with an enlargement of the right upper extremity. Electromyography showed
      polyphasic, large motor unit potentials in the affected muscles. MRI and
      ultrasound assessment demonstrated diffuse enlargement of muscle mass without
      signs of edema. Muscle biopsy revealed sections with marked variations in fiber
      size with no signs of inflammation or marked loss of muscle fibers. Factors
      assumed to be important in the pathophysiology of this phenomenon are discussed.

PMID- 19751977
TI  - Myasthenia gravis precipitated by trauma: latent myasthenia and the concept of
      'threshold'.
AB  - Myasthenia gravis is caused by antibodies to post-synaptic neuromuscular junction
      proteins, most commonly nicotinic acetylcholine receptors. Evidence indicates
      that acetylcholine receptor antibodies must be present in the circulation prior
      to the development of clinical or neurophysiological manifestations of
      myasthenia. We describe the onset of seropositive myasthenia within minutes of
      minor trauma to the chest and neck in a previously asymptomatic 68-year-old man,
      followed by protracted disease with persistent antibodies. Such rapid evolution
      of myasthenia following an identifiable stimulus has not been reported previously
      and suggests a humoral mechanism. We speculate that the remote effects of
      autoinflammation secondary to tissue microtrauma led to a sudden increase in
      muscle permeability and greater exposure of receptors to antibody, with resulting
      acute impairment of neuromuscular transmission. We also suggest that the trauma
      might have resulted in increased antibody production by remnant thymic tissue,
      leading to chronic isease.

PMID- 19751978
TI  - Total knee arthroplasty and Crigler-Najjar syndrome: a case report.
AB  - Crigler-Najjar (CN) syndrome is a rare genetic disease characterized by
      hyperbilirubinemia due to a deficiency in the hepatic enzyme UDP-glucuronosyl
      transferase. We describe the first case of total knee arthroplasty in a patient
      with CN syndrome (type II). This procedure was complicated by kernicterus 1 week
      after hospital discharge. He also developed Klebsiella bacteremia and sepsis,
      requiring a brief ICU stay. He was discharged in good condition 2 months later.
      It is evident that physicians involved in the care of patients with CN syndrome
      in the peri-operative period need to have a high index of suspicion for the
      development of severe hyperbilirubinemia and kernicterus in order to
      appropriately manage and, possibly, prevent this complication. A literature
      review and intra-operative observations provide insight into the possible
      relationship between hyperbilirubinemia and osteoarthritis as well as the peri
      operative considerations to be made for this group of patients.

PMID- 19751979
TI  - Validation of the Thessaly test for detecting meniscal tears in anterior cruciate
      deficient knees.
AB  - Meniscal injuries are frequently associated with anterior cruciate ligament (ACL)
      tears. Clinical tests that are useful for detecting meniscal tears may not be
      valid in this setting. The Thessaly test, a newly described dynamic clinical
      examination, has been shown to have a very high diagnostic accuracy for detecting
      meniscal tears. This study evaluates the accuracy of the Thessaly test in
      patients with combined ACL and meniscus injuries. We examined eighty patients
      with ACL deficiency for meniscal injuries using the Thessaly test (at 20 degrees
      of knee flexion), the lateral and medial joint line tenderness tests, and the
      McMurray test. Examiners were blinded to the MRI report on the conditions of the
      menisci. All patients underwent arthroscopic ACL reconstruction during which the
      menisci were evaluated by direct vision and probing. During the Thessaly test,
      six patients developed severe pain and could not complete the test. Sensitivity,
      specificity, likelihood ratios and predictive values were calculated for all
      tests. The Thessaly test had a sensitivity of 79%, specificity of 40%, positive
      predictive value of 56%, negative predictive value of 66%, positive likelihood
      ratio of 1.33, negative likelihood ratio of 0.51%, and overall accuracy of 60%.
      We concluded that the Thesally test has a low specificity in patients with
      combined ACL and meniscal injuries and can not be recommended as a diagnostic
      test in this setting.

PMID- 19751980
TI  - 3- and 6-Substituted 2-amino-4,5,6,7-tetrahydrothieno[2,3-c]pyridines as A1
      adenosine receptor allosteric modulators and antagonists.
AB  - A series of 2-amino-4,5,6,7-tetrahydrothieno[2,3-c]pyridines were prepared and
      evaluated as potential allosteric modulators at the A(1) adenosine receptor. The
      structure-activity relationships of the 3- and 6-positions of a series of 2-amino
      4,5,6,7-tetrahydrothieno[2,3-c]pyridines were explored. Despite finding that 3-
      and 6-substituted 2-amino-4,5,6,7-tetrahydrothieno[2,3-c]pyridines possess the
      ability to recognize an allosteric site on the agonist-occupied A(1)AR at
      relatively high concentrations, the structural modifications we have performed on
      this scaffold favor the expression of orthosteric antagonist properties over
      allosteric properties. This research has identified 2-amino-4,5,6,7
      tetrahydrothieno[2,3-c]pyridines as novel class of orthosteric antagonist of the
      A(1)AR and highlighted the close relationship between structural elements
      governing allosteric modulation and orthosteric antagonism of agonist function at
      the A(1)AR.

PMID- 19751981
TI  - Comment on "Is there a benefit of frequent CT follow-up after EVAR"?

PMID- 19751982
TI  - Comparison of ankle-brachial index measured by an automated oscillometric
      apparatus with that by standard Doppler technique in vascular patients.
AB  - OBJECTIVES: To evaluate the determination of ankle-brachial indices (ABIs) using
      a simple automated ankle pressure measurement device in comparison with the
      Doppler technique. DESIGN: ABI was measured in 61 patients (122 legs) admitted to
      the department of vascular surgery, Rigshospitalet. ABI was calculated twice
      using both the methods on both legs. MATERIALS AND METHODS: We tested the
      automated oscillometric blood pressure device, CASMED 740, for measuring ankle
      and arm blood pressure and compared it with the current gold standard, the hand
      held Doppler technique, by the Bland-Altman analysis. RESULTS: Using the Doppler
      derived ABI as the gold standard, the sensitivity and specificity of the
      oscillometric method for determining an ABI<or=0.9 is 71% and 92%, respectively.
      The overall accuracy for correctly identifying an ABI of 0.9 with the
      oscillometric method was 82%. Ankle pressures measured by CASMED 740 were
      systematically higher in patients with reduced ankle pressures, but accurate in
      patients with ankle pressures above 90 mm Hg. CONCLUSION: Automated oscillometric
      assessment of ankle blood pressure and ABI may falsely categorise PAD patients as
      having a normal ankle pressure and ABI.

PMID- 19751983
TI  - Serum haptoglobin concentrations in dairy cattle with lameness due to claw
      disorders.
AB  - In cattle, elevated blood serum concentrations of haptoglobin, an acute phase
      protein, have been demonstrated in association with several diseases, but not
      with lameness. Serum haptoglobin was measured in 60 Holstein dairy cattle
      diagnosed with lameness due to four claw disorders, pododermatitis septica (PS;
      n=41), pododermatitis circumscripta (PC; n=8), interdigital necrobacillosis (IN;
      n=7), papillomatous digital dermatitis (PDD; n=4). Haptoglobin was measured on
      day 1 (0-3 days after lameness was observed but before treatment) and on days 3
      and 5. A total of 10 healthy cows served as controls (haptoglobin values <1.0
      mg/dL). Each of the claw disorders was associated with elevated haptoglobin on
      day 1 (PS, PC, IN and PDD: 65.9%, 37.5%, 71.4% and 25.0%, respectively). Trimming
      and antibiotic treatment led to a reduction in the number of PS and IN cows with
      increased haptoglobin concentrations, respectively (P<0.05), but trimming did not
      lead to any reduction in cows with PC. The study showed that lameness due to claw
      disorders can be associated with a systemic acute phase response and elevated
      serum haptoglobin in dairy cattle. Based on the course of haptoglobin, treatments
      seemed effective for all claw disorders except for PC.

PMID- 19751984
TI  - Comparison of pressure plate and force plate gait kinetics in sound Warmbloods at
      walk and trot.
AB  - Modern pressure plates (PP) could be an alternative to traditional force plates
      (FP) for quantitative equine gait analysis, thereby providing the clinician with
      objective data on the horse's gait while unravelling the loading of different
      regions of the hoof during the stance phase. The aim of this study was to
      determine whether a stand-alone PP allows reliable measurement of gait kinetics,
      compared to simultaneously recorded FP variables. Six sound Warmblood horses were
      walked and trotted over a combined PP and FP system for collection of a set of
      five valid kinetic measurements for each forelimb. A measurement was considered
      valid if the horse was moving in a straight line at a constant pace while gait
      velocity was within a preset range and the hoof fully contacted the plate
      surface. Significant differences between FP and PP data were seen for peak
      vertical force (PVF), vertical impulse (VI), time at which the PVF occurs (tPVF)
      and forelimb symmetry ratios (SymPVF and SymVI) (P < 0.05), but not for stance
      phase duration (ST). Nevertheless, mean agreement indices (AIs) of ST, tPVF and
      SymPVF and SymVI were excellent (>= 0.92), whereas AIs of PVF and VI were
      moderate (>= 0.70). The excellent agreement between PP and FP symmetry ratios
      confirms that observed differences between PP and FP in symmetry ratios are small
      (2-7%), especially when compared to the expected decrease in symmetry associated
      with mild lameness (> 20%). The results indicate that a stand-alone pressure
      plate can be used to measure absolute (ST) and relative (tPVF) temporal variables
      and loading symmetry ratios and offers equine veterinarians a mobile, cost
      efficient and quick gait evaluation method for routine clinical use. However, the
      system cannot be used interchangeably with a force plate to measure absolute
      values of limb loading.

PMID- 19751985
TI  - Acquired urinary incontinence in the bitch: update and perspectives from human
      medicine. Part 1: The bladder component, pathophysiology and medical treatment.
AB  - Micturition disorders are commonly encountered in veterinary medicine and can be
      divided into two main categories, namely, urinary incontinence and urinary
      retention. Various pathologies can affect the bladder and/or urethral
      contractility causing symptoms of urinary incontinence. In this first part of a
      three-part review, the different causes of urinary incontinence, the physiology
      of the lower urinary tract and impaired bladder contractility are reviewed. Since
      urinary incontinence due to overactive bladder syndrome or detrusor atony is
      described in both dogs and humans, the different therapeutic targets in the
      treatment of impaired bladder contractility in human and veterinary medicine are
      discussed.

PMID- 19751986
TI  - Thin-film solid-state proton NMR measurements using a synthetic mica substrate:
      polymer blends.
AB  - Solid-state proton nuclear magnetic resonance (NMR) measurements are performed
      successfully on polymer blend thin films through the use of synthetic mica as a
      substrate. When used as a substrate, synthetic fluorophlogopite mica with its
      proton-free, diamagnetic character, allows for adequate measurement sensitivity
      while minimally perturbing the proton thin-film spectra, especially relative to
      more commonly available natural micas. Specifically, we use multiple-pulse
      techniques in the presence of magic-angle spinning to measure the degree of
      mixing in two different polymer blend thin films, polystyrene/poly(xylylene
      ether) and poly(1-methyladamantyl methacrylate) (PMAdMA)/triphenylsulfonium
      perfluorobutanesulfonate (TPS-PFBS), spin-coated onto mica substrates. Our
      earlier studies had focused on bulk systems where NMR signals are stronger, but
      may not be representative of thin films of the same systems that are relevant to
      many applications such as photoresist formulations in the electronics industry.
      The superiority of synthetic over natural paramagnetic mica is demonstrated by
      the maintenance of resolution and spinning sideband intensities (relative to bulk
      samples) for the synthetic mica samples. In contrast, degraded resolution and
      large spinning sidebands are shown to typify spectra of the natural mica samples.
      This approach can be applied to many other proton measurements of solid thin
      films, thereby greatly extending the types of systems to be investigated.
      Magnetic susceptibility measurements are also reported for all micas used.

PMID- 19751988
TI  - Numerical simulations of acoustic cavitation noise with the temporal fluctuation
      in the number of bubbles.
AB  - Numerical simulations of cavitation noise have been performed under the
      experimental conditions reported by Ashokkumar et al. (2007) [26]. The results of
      numerical simulations have indicated that the temporal fluctuation in the number
      of bubbles results in the broad-band noise. "Transient" cavitation bubbles, which
      disintegrate into daughter bubbles mostly in a few acoustic cycles, generate the
      broad-band noise as their short lifetimes cause the temporal fluctuation in the
      number of bubbles. Not only active bubbles in light emission (sonoluminescence)
      and chemical reactions but also inactive bubbles generate the broad-band noise.
      On the other hand, "stable" cavitation bubbles do not generate the broad-band
      noise. The weaker broad-band noise from a low-concentration surfactant solution
      compared to that from pure water observed experimentally by Ashokkumar et al. is
      caused by the fact that most bubbles are shape stable in a low-concentration
      surfactant solution due to the smaller ambient radii than those in pure water.
      For a relatively high number density of bubbles, the bubble-bubble interaction
      intensifies the broad-band noise. Harmonics in cavitation noise are generated by
      both "stable" and "transient" cavitation bubbles which pulsate nonlinearly with
      the period of ultrasound.

PMID- 19751987
TI  - Characterization of an MPS I-H knock-in mouse that carries a nonsense mutation
      analogous to the human IDUA-W402X mutation.
AB  - Here we report the characterization of a knock-in mouse model for the autosomal
      recessive disorder mucopolysaccharidosis type I-Hurler (MPS I-H), also known as
      Hurler syndrome. MPS I-H is the most severe form of alpha-l-iduronidase
      deficiency. alpha-l-iduronidase (encoded by the IDUA gene) is a lysosomal enzyme
      that participates in the degradation of dermatan sulfate and heparan sulfate.
      Using gene replacement methodology, a nucleotide change was introduced into the
      mouse Idua locus that resulted in a nonsense mutation at codon W392. The Idua
      W392X mutation is analogous to the human IDUA-W402X mutation commonly found in
      MPS I-H patients. We found that the phenotype in homozygous Idua-W392X mice
      closely correlated with the human MPS I-H disease. Homozygous W392X mice showed
      no detectable alpha-l-iduronidase activity. We observed a defect in GAG
      degradation as evidenced by an increase in sulfated GAGs excreted in the urine
      and stored in multiple tissues. Histology and electron microscopy also revealed
      evidence of GAG storage in all tissues examined. Additional assessment revealed
      bone abnormalities and altered metabolism within the Idua-W392X mouse. This new
      mouse will provide an important tool to investigate therapeutic approaches for
      MPS I-H that cannot be addressed using current MPS I-H animal models.

PMID- 19751989
TI  - Ultrasonic assisted synthesis, characterization and influence factors of
      monodispersed dumbbell-like YF(3) nanostructures.
AB  - In the present paper, we reported the successful synthesis of dumbbell-like YF(3)
      nanostructures with a high yield in a mixed system of water/N,N-dimethylformamide
      (DMF) under the assistance of ultrasound waves of 40kHz with the ultrasonic power
      of 100% (200W) at 65 degrees C for 2h, employing Y(2)O(3) (99.99%) and NH(4)F as
      the starting reactants. The product was characterized by means of powder X-ray
      diffraction (XRD), energy dispersive spectrometry (EDS), transmission electron
      microscopy (TEM), selected area electron diffraction (SAED) pattern and field
      emission scanning electron microscopy (SEM). Some factors influencing the
      morphology of YF(3) nanostructures, including the ultrasonic time and power, the
      amount of NH(4)F, and the ratio of water/DMF, were systematically investigated.
      Research showed that the morphology of YF(3) could be tuned by the volume ratio
      of water/DMF. The roles of DMF and the ultrasonic wave in the formation of YF(3)
      nanostructures were discussed.

PMID- 19751990
TI  - Postoperative memory prediction in left temporal lobe epilepsy: the Wada test is
      of no added value to preoperative neuropsychological assessment and MRI.
AB  - The contribution of the Wada test (intracarotid amytal procedure, IAP) to
      predicting postoperative memory outcome in left temporal lobe epilepsy (LTLE) is
      becoming increasingly controversial when preoperative neuropsychological
      evaluation and MRI findings are available. We retrospectively analyzed 59
      patients with LTLE who underwent en bloc temporal lobe resection. All patients
      had valid bilateral IAP test results, complete pre- and postoperative
      neuropsychological evaluation, and MRI grading on a 5-point scale integrating T 2
      signal increase and degree of atrophy. Thirty percent of patients showed
      postoperative memory decline. Multiple regression analysis revealed that
      significant predictors of decline [F(2.56)=22.71, P<0.001, r(2)=0.448] included
      preoperative memory learning score [t=-5.89, P<0.001] and MRI classification
      [t=3.10, P<0.003], but not IAP scores. The IAP is of no added value in the
      prediction of postoperative memory outcome in LTLE in the presence of
      comprehensive neuropsychological and MRI data.

PMID- 19751991
TI  - A survey of public knowledge, attitudes, and practices with respect to epilepsy
      in Badissa village, centre region of Cameroon.
AB  - OBJECTIVE: The aim of this study was to assess knowledge, attitudes, and
      practices (KAP) with respect to epilepsy in Badissa, as part of a series of
      studies mandated by the Cameroon Ministry of Public Health. METHOD: We
      interviewed 164 subjects face-to-face during a door-to-door survey. RESULTS: All
      of the subjects had heard about epilepsy; 98.8% knew at least one patient with
      epilepsy, and 97.6% had seen at least one epileptic seizure. With respect to
      attitudes, 16% and 32% would respectively prevent their children from associating
      with and marrying, people with epilepsy; 55.5% would offer people with epilepsy
      equal employment. The independent determinants of attitudes were the belief that
      epilepsy is a form of insanity (P=0.004) or is caused by a mental illness
      (P=0.003), having read about epilepsy (P=0.018), and being married (P=0.007).
      CONCLUSIONS: Our study demonstrates a high level of awareness and fairly good
      knowledge of epilepsy, a lower level of misconceptions, and better attitudes, in
      the study area confirming our hypothesis of a regional variation in these
      characteristics. This model of care may be useful in scaling up the epilepsy
      education program in Cameroon.

PMID- 19751992
TI  - Impact of antiepileptic drugs on cognition, behavior, and motor skills in
      children with new-onset, idiopathic epilepsy.
AB  - OBJECTIVE: As treatment options for epilepsy have increased, there has been a
      commensurate increase in interest in the side effect profiles of these drugs.
      METHODS: In this study, children between the ages of 6 and 17 with a diagnosis of
      new-onset, idiopathic epilepsy were evaluated at baseline (n=57) and 6 (n=45) and
      12 (n=31) months after initiation of antiepileptic drug therapy. RESULTS: There
      was improvement in the cognitive functioning of children after 12 months of
      treatment. A transient drop in performance of children with generalized seizures
      (10 of 11 of whom had absence seizures) at 6 months may have been due to
      persistent seizures, the drugs used to treat them (predominantly ethosuximide),
      or both. Worsening of reaction time and reaction time variability in the focal
      seizure group, the only scores showing persistent deterioration over 12 months,
      may be attributable to the medications used for this group, the most common of
      which was carbamazepine. CONCLUSIONS: There were few adverse effects of
      antiepileptic drug treatment in the group followed over 12 months. Carbamazepine
      may have been responsible for persistent impairment of reaction time and reaction
      time variability.

PMID- 19751994
TI  - A new iterative learning controller using variable structure fourier neural
      network.
AB  - A new iterative learning control approach based on Fourier neural network (FNN)
      is presented for the tracking control of a class of nonlinear systems with
      deterministic uncertainties. The proposed controller consists of two loops. The
      inner loop is a feedback control action that decreases system variability and
      reduces the influence of random disturbances. The outer loop is an FNN-based
      learning controller that generates the system input to suppress the error caused
      by system nonlinearities and deterministic uncertainties. The FNN employs
      orthogonal complex Fourier exponentials as its activation functions. Therefore,
      it is essentially a frequency-domain method that converts the tracking problem in
      the time domain into a number of regulation problems in the frequency domain.
      Through a novel phase compensation technique, this model-free method makes it
      possible to use higher-frequency components in the FNN to improve the tracking
      performance. In addition, the structure of the FNN can be reconfigured according
      to the system output information to make the learning more efficient and increase
      the convergent speed of the tracking error. Experiments on both a commercial gear
      box and a belt-driven positioning table are conducted to show the effectiveness
      of the proposed controller.

PMID- 19751993
TI  - Vagal afferent nerves with the properties of nociceptors.
AB  - Vagal afferent nerves are essential for optimal neural regulation of visceral
      organs, but are not often considered important for their defense. However, there
      are well-defined subsets of vagal afferent nerves that have activation properties
      indicative of specialization to detect potentially harmful stimuli (nociceptors).
      This is clearly exemplified by the vagal bronchopulmonary C-fibers that are
      quiescent in healthy lungs but are readily activated by noxious chemicals and
      inflammatory molecules. Vagal afferent nerves with similar activation properties
      have been also identified in the esophagus and probably exist in other visceral
      tissues. In addition, these putative vagal nociceptors often initiate defensive
      reflexes, can be sensitized, and have the capacity to induce central
      sensitization. This set of properties is a characteristic of nociceptors in
      somatic tissues.

PMID- 19751995
TI  - Pipelined chebyshev functional link artificial recurrent neural network for
      nonlinear adaptive filter.
AB  - A novel nonlinear adaptive filter with pipelined Chebyshev functional link
      artificial recurrent neural network (PCFLARNN) is presented in this paper, which
      uses a modification real-time recurrent learning algorithm. The PCFLARNN consists
      of a number of simple small-scale Chebyshev functional link artificial recurrent
      neural network (CFLARNN) modules. Compared to the standard recurrent neural
      network (RNN), those modules of PCFLARNN can simultaneously be performed in a
      pipelined parallelism fashion, and this would lead to a significant improvement
      in its total computational efficiency. Furthermore, contrasted with the
      architecture of a pipelined RNN (PRNN), each module of PCFLARNN is a CFLARNN
      whose nonlinearity is introduced by enhancing the input pattern with Chebyshev
      functional expansion, whereas the RNN of each module in PRNN utilizing linear
      input and first-order recurrent term only fails to utilize the high-order terms
      of inputs. Therefore, the performance of PCFLARNN can further be improved at the
      cost of a slightly increased computational complexity. In addition, due to the
      introduced nonlinear functional expansion of each module in PRNN, the number of
      input signals can be reduced. Computer simulations have demonstrated that the
      proposed filter performs better than PRNN and RNN for nonlinear colored signal
      prediction, nonstationary speech signal prediction, and chaotic time series
      prediction.

PMID- 19751996
TI  - [Extracranial stereotactic radiotherapy avancer by robotic radiosurgery:
      preliminary experience of the center Alexis-Vautrin].
AB  - Stereotactic radiotherapy delivers allows for a highly precise irradiation, and
      was originally developed in the 70s by neurosurgeons. Gradually, it has been
      developed in extracranial indications. Moreover new innovative treatment devices
      such as the robotic radiosurgery with CyberKnife have emerged. Indications are
      currently being validated by the HAS in intracranial locations that are treated
      by conventional radiosurgery for several decades. Three robotic radiosurgery
      facilities were opened in France in 2006 thanks to a grant from the INCa. Those
      are posed in Lille, Nice, Nancy. Since 2007, 140 patients were treated as off
      today in Alexis Vautrin Cancer Center (40 intracranial locations, 100
      extracranial). Thirty five primitive lung cancer or pulmonary metastasis, twenty
      primary liver tumor or metastasis, 21 spinal locations (schwanomas or bone
      metastasis), and nineteen other (pelvic lymph nodes, chordomas, H&N, etc.). The
      lung diseases were treated on the 80% isodose as follow: 60 Gy in three fractions
      for peripheral tumors and 54 Gy for central ones. The one-year local control rate
      reaches 90%. The hepatic tumors received 45 Gy in three fractions prescribed on
      the 80% isodose with a six months local control rate of 83%. Any of the 140
      patients has suffered from acute or late toxicity > grade 3. These encouraging
      outcomes are confirmed by both other French centers and phase II trial are
      pending to assess the most effective and safe radiations protocols.

PMID- 19751997
TI  - [Cancer genetics: estimation of the needs of the population in France for the
      next ten years].
AB  - Organised since 1990 in France, cancer genetics has been strengthened since 2003
      by the programme "Plan Cancer" which resulted in an improvement of the
      organisation of activities. The aim of this review is to present an update of the
      estimation of the needs of the population in this field for the next ten years,
      provided by a group of experts mandated by the French National Cancer Institute.
      Identification and management of major hereditary predispositions to cancer have
      a major impact on decrease in mortality and incidence. Sensitivity of criteria
      for the detection of BRCA1/2 mutations could be substantially improved by
      enlarging the indication for genetic testing to isolated cases of ovarian cancer
      occurring before 70 years and to familial cases occurring after this age limit.
      In the Lynch syndrome, the present criteria would have an excellent sensitivity
      for the detection of mutations in the mismatch repair (MMR) genes if the pre
      screening of tumours on microsatellite instability (MSI) phenotype was effective,
      but these criteria are actually poorly applied. However, genetic testing should
      not be proposed to all the patients affected by tumours belonging to the spectrum
      of major predispositions and a fortiori to unaffected persons unless an affected
      relative has been identified as a carrier. The prescription of tests should
      continue to be strictly controlled and organised, in patients as well as in at
      risk relatives. The enlargement of criteria and the improvement in the spreading
      of recommendations should result in an increase of genetic counselling activity
      and of the prescriptions of tests by a factor 2 to 4, and to a lesser extent in
      the clinical management of at risk persons. In a near future, it appears
      important to mandate experts on specific issues such as the determinants of the
      lack of effective application of tumour screening for MSI phenotype, the
      recommendations for the identification and the management of MYH-associated
      polyposis, or the predictive value of tumour characteristics for the
      identification of BRCA1/2 mutations. The expected increase in cancer genetics
      activity will need an optimal organisation to increase the throughput. Such
      measures will help in facing up to new predispositions that will probably be
      identified in common cancers.

PMID- 19751998
TI  - Newspaper content analysis in evaluation of a community-based participatory
      project to increase physical activity.
AB  - This study conducted a newspaper content analysis as part of an evaluation of a
      community-based participatory research project focused on increasing physical
      activity through policy and environmental changes, which included activities
      related to media advocacy and media-based community education. Daily papers (May
      2003 to December 2005) from both the intervention and comparison counties were
      reviewed for topics related to physical activity and an active living environment
      (e.g. safety, policy, urban design, transportation and recreational resources). A
      total of 2681 articles from 1764 newspapers were analyzed. The intervention
      county had a greater proportion of articles on the selected topics. Specifically,
      the intervention county had a greater proportion of articles in topics related to
      safety, policy and community initiatives, as well as in sidewalks and
      recreational facilities; both priority areas for the intervention. Prominence of
      the articles was assessed using a composite index score. Generally, prominence of
      the topics analyzed was low. Articles in the sidewalks and recreational
      facilities topic category in the intervention county had higher prominence scores
      on average than the comparison county. The study demonstrates that media content
      analysis can be a valuable component in evaluating community-based interventions.

PMID- 19751999
TI  - The effect of a multi-strategy workplace physical activity intervention promoting
      pedometer use and step count increase.
AB  - Pedometer use and step count goals have become popular in physical activity (PA)
      interventions in different settings. Previous pedometer-based workplace
      interventions were short term, uncontrolled and executed outside Europe. This
      European quasi-experimental study evaluated the effects of a 20-week pedometer
      based PA workplace intervention. Pedometer-based and self-reported PA from one
      intervention worksite (68 participants at follow-up) was compared with the data
      of a comparison workplace (79 participants at follow-up). A downward trend in
      overall step counts from baseline (end of summer) to follow-up (winter) was found
      (F = 3.3, P = 0.071). However, the intervention effect revealed a significant
      smaller decrease in the intervention workplace (-618 steps/day) than in the
      comparison workplace (-1389 steps/day) (F = 8.8, P = 0.004). This intervention
      effect was only present in already active participants, reaching 10 000 steps/day
      at baseline (intervention participants: -1706 steps/day; comparison participants:
      -4006 steps/day) (F = 5.5, P = 0.023). Overall project awareness was very high
      (97%) and the intervention strategies were judged 'good to very good' by 57-95%
      of the participants. However, the proportion of intervention participants
      reporting that they had changed their PA behavior because of the intervention
      (31%) and reporting that they had used the pedometer during the intervention
      (48%) was limited. Future workplace projects should give extra attention to
      inactive employees.

PMID- 19752000
TI  - Impact of a campaign on the public's attitudes towards depression.
AB  - A public campaign was launched in 2000 as part of the four-level community-based
      intervention 'Nuremberg Alliance Against Depression' (NAD) in Nuremberg, Germany.
      Evaluation results will be presented. A baseline survey was done before the
      campaign in Nuremberg and Wuerzburg (control region), two surveys followed 10 and
      22 months after the implementation. Multiple regression analyses were performed,
      with time, place and the interaction of time and location as independent and the
      corresponding items as dependent variables. For the general population, the
      campaign was successful in creating awareness for the NAD. For persons who
      reported experience with depression and persons aware of the NAD, analyses showed
      positive desirable effects: more awareness of depression and the NAD. In
      addition, among those aware, more positive attitudes towards medication treatment
      and antidepressants developed and also 'lack of self-discipline' declined as
      causal explanation as did the notion 'pull yourself together' as treatment
      option. The campaign induced relevant changes mainly in persons aware of the NAD
      and persons who reported to have had experience with depression. The fact that
      many of the changes in the general population declined in the second year of the
      campaign, when activities were done with lower intensity, illustrates the need
      for permanent depression awareness action.

PMID- 19752001
TI  - Fulvestrant in advanced male breast cancer.

PMID- 19752002
TI  - Bone morphogenetic proteins and zoledronic acid.

PMID- 19752003
TI  - Nasal septum perforation in a breast cancer patient treated with bevacizumab.

PMID- 19752004
TI  - Essential thrombocythemia transforming into acute biphenotypic leukemia in a
      patient on hydroxyurea monotherapy.

PMID- 19752005
TI  - Systematic comparative protein expression profiling of clear cell renal cell
      carcinoma: a pilot study based on the separation of tissue specimens by two
      dimensional gel electrophoresis.
AB  - Proteome-based technologies represent powerful tools for the analysis of protein
      expression profiles, including the identification of potential cancer candidate
      biomarkers. Thus, here we provide a comprehensive protein expression map for
      clear cell renal cell carcinoma established by systematic comparative two
      dimensional gel electrophoresis-based protein expression profiling of 16 paired
      tissue systems comprising clear cell renal cell carcinoma lesions and
      corresponding tumor-adjacent renal epithelium using overlapping narrow pH
      gradients. This approach led to the mapping of 348 distinct spots corresponding
      to 248 different protein identities. By implementing restriction criteria
      concerning their detection frequency and overall regulation mode, 28 up- and 56
      down-regulated single target spots were considered as potential candidate
      biomarkers. Based on their gene ontology information, these differentially
      expressed proteins were classified into distinct functional groups and according
      to their cellular distribution. Moreover, three representative members of this
      group, namely calbindin, gelsolin, and heart fatty acid-binding protein, were
      selected, and their expression pattern was analyzed by immunohistochemistry using
      tissue microarrays. Thus, this pilot study provides a significant update of the
      current renal cell carcinoma map and defines a number of differentially expressed
      proteins, but both their potential as candidate biomarkers and clinical relevance
      has to be further explored in tissues and for body fluids like serum and urine.

PMID- 19752006
TI  - IDEAL-Q, an automated tool for label-free quantitation analysis using an
      efficient peptide alignment approach and spectral data validation.
AB  - In this study, we present a fully automated tool, called IDEAL-Q, for label-free
      quantitation analysis. It accepts raw data in the standard mzXML format as well
      as search results from major search engines, including Mascot, SEQUEST, and
      X!Tandem, as input data. To quantify as many identified peptides as possible,
      IDEAL-Q uses an efficient algorithm to predict the elution time of a peptide
      unidentified in a specific LC-MS/MS run but identified in other runs. Then, the
      predicted elution time is used to detect peak clusters of the assigned peptide.
      Detected peptide peaks are processed by statistical and computational methods and
      further validated by signal-to-noise ratio, charge state, and isotopic
      distribution criteria (SCI validation) to filter out noisy data. The performance
      of IDEAL-Q has been evaluated by several experiments. First, a serially diluted
      protein mixed with Escherichia coli lysate showed a high correlation with
      expected ratios and demonstrated good linearity (R(2) = 0.996). Second, in a
      biological replicate experiment on the THP-1 cell lysate, IDEAL-Q quantified 87%
      (1,672 peptides) of all identified peptides, surpassing the 45.7% (909 peptides)
      achieved by the conventional identity-based approach, which only quantifies
      peptides identified in all LC-MS/MS runs. Manual validation on all 11,940 peptide
      ions in six replicate LC-MS/MS runs revealed that 97.8% of the peptide ions were
      correctly aligned, and 93.3% were correctly validated by SCI. Thus, the mean of
      the protein ratio, 1.00 +/- 0.05, demonstrates the high accuracy of IDEAL-Q
      without human intervention. Finally, IDEAL-Q was applied again to the biological
      replicate experiment but with an additional SDS-PAGE step to show its
      compatibility for label-free experiments with fractionation. For flexible
      workflow design, IDEAL-Q supports different fractionation strategies and various
      normalization schemes, including multiple spiked internal standards. User
      friendly interfaces are provided to facilitate convenient inspection, validation,
      and modification of quantitation results. In summary, IDEAL-Q is an efficient,
      user-friendly, and robust quantitation tool. It is available for download.

PMID- 19752007
TI  - Epigenetics in cancer.
AB  - Epigenetic mechanisms are essential for normal development and maintenance of
      tissue-specific gene expression patterns in mammals. Disruption of epigenetic
      processes can lead to altered gene function and malignant cellular
      transformation. Global changes in the epigenetic landscape are a hallmark of
      cancer. The initiation and progression of cancer, traditionally seen as a genetic
      disease, is now realized to involve epigenetic abnormalities along with genetic
      alterations. Recent advancements in the rapidly evolving field of cancer
      epigenetics have shown extensive reprogramming of every component of the
      epigenetic machinery in cancer including DNA methylation, histone modifications,
      nucleosome positioning and non-coding RNAs, specifically microRNA expression. The
      reversible nature of epigenetic aberrations has led to the emergence of the
      promising field of epigenetic therapy, which is already making progress with the
      recent FDA approval of three epigenetic drugs for cancer treatment. In this
      review, we discuss the current understanding of alterations in the epigenetic
      landscape that occur in cancer compared with normal cells, the roles of these
      changes in cancer initiation and progression, including the cancer stem cell
      model, and the potential use of this knowledge in designing more effective
      treatment strategies.

PMID- 19752008
TI  - Small cell carcinoma of the lung: an incidental finding on routine cardiac
      imaging.
AB  - We describe a case of small cell carcinoma of the lung presenting as a
      mediastinal mass detected incidentally on transthoracic echocardiography and
      nuclear SPECT imaging.

PMID- 19752009
TI  - Usefulness of 3D transoesophageal echocardiography for guiding wires and closure
      devices in mitral perivalvular leaks.
AB  - Sixty-three-year-old male patient. Previous history of rheumatic valvular
      disease. He underwent multiple mitral and aortic valve replacements. Nowadays, he
      presents a periprosthetic mitral leak. He underwent a leak closure by using a
      percutaneous approach. During the procedure, the superiority of 3D TEE over 2D
      TEE was confirmed for wires and device positioning, excluding interference with
      the prosthesis discs and evaluating the residual periprosthetic regurgitation.

PMID- 19752010
TI  - The association between childhood trauma and memory functioning in schizophrenia.
AB  - OBJECTIVE: Both neurocognitive impairments and a history of childhood abuse are
      highly prevalent in patients with schizophrenia. Childhood trauma has been
      associated with memory impairment as well as hippocampal volume reduction in
      adult survivors. The aim of the following study was to examine the contribution
      of childhood adversity to verbal memory functioning in people with schizophrenia.
      METHODS: Eighty-five outpatients with a Diagnostic and Statistical Manual of
      Mental Disorders (Fourth Edition) diagnosis of chronic schizophrenia were
      separated into 2 groups on the basis of self-reports of childhood trauma.
      Performance on measures of episodic narrative memory, list learning, and working
      memory was then compared using multivariate analysis of covariance. RESULTS:
      Thirty-eight (45%) participants reported moderate to severe levels of childhood
      adversity, while 47 (55%) reported no or low levels of childhood adversity. After
      controlling for premorbid IQ and current depressive symptoms, the childhood
      trauma group had significantly poorer working memory and episodic narrative
      memory. However, list learning was similar between groups. CONCLUSION: Childhood
      trauma is an important variable that can contribute to specific ongoing memory
      impairments in schizophrenia.

PMID- 19752011
TI  - Device diagnostics and long-term clinical outcome in patients receiving cardiac
      resynchronization therapy.
AB  - AIMS: This retrospective analysis sought to develop and validate a model using
      the measured diagnostic variables in cardiac resynchronization therapy (CRT)
      devices to predict mortality. METHODS AND RESULTS: Data used in this analysis
      came from two CRT studies: Cardiac Resynchronization Therapy Registry Evaluating
      Patient Response with RENEWAL Family Devices (CRT RENEWAL) (n = 436) and Heart
      Failure-Heart Rate Variability (HF-HRV) (n = 838). Patients from CRT RENEWAL were
      used to create a model for risk of death using logistic regression and to create
      a scoring system that could be used to predict mortality. Results of both the
      logistic regression and the clinical risk score were validated in a cohort of
      patients from the HF-HRV study. Diagnostics significantly improved over time post
      CRT implant (all P < 0.001) and were correlated with a trend of decreased risk of
      death. The regression model classified CRT RENEWAL patients into low (2.8%),
      moderate (6.9%), and high (13.8%) risk of death based on tertiles of their model
      predicted risk. The clinical risk score classified CRT RENEWAL patients into low
      (2.8%), moderate (10.1%), and high (13.4%) risk of death based on tertiles of
      their score. When both the regression model and the clinical risk score were
      applied to the HF-HRV study, each was able to classify patients into appropriate
      levels of risk. CONCLUSION: Device diagnostics may be used to create models that
      predict the risk of death.

PMID- 19752012
TI  - Sound ideas of Herman Snick, a superb clinician and critical investigator.

PMID- 19752013
TI  - How to demonstrate that eSET does not compromise the likelihood of having a baby?
AB  - BACKGROUND: In several randomized studies, elective single embryo transfer (eSET)
      has proven its effectiveness in reducing twin pregnancy rates while obtaining
      acceptable overall pregnancy rates. However, there is no outcome measurement
      consensus to evaluate the effectiveness of eSET versus double-embryo transfer
      (DET). METHODS: This study evaluated whether or not adopting an eSET strategy
      instead of a DET strategy lowers the probability of having at least one live-born
      infant in good prognosis couples. Seven hundred and twenty-six couples were
      divided into two groups. The retrospective arm of the study was undertaken on the
      first group of couples (n = 483, DET group) and the prospective arm performed on
      the second group of couples (n = 243, SET group). In these specific populations,
      the probability of a woman having at least one live-born infant and the
      probability that one embryo utilized leads to a child were the main outcome
      measures. RESULTS: The probability of a woman having at least one live-born
      infant was 60.5% in the DET group compared with 60.8% in the SET group. The
      probability of a live-born child per embryo utilized was not significantly
      different between the SET and the DET groups, 18.9% and 17.6%, respectively. In
      addition, the cumulative multiple live birth rate was significantly lower in the
      SET compared with the DET group. CONCLUSIONS: In this observational study, using
      appropriate cryopreservation techniques, the chance of delivering a live baby,
      per utilized embryo, in an elective SET strategy is as good as that for DET.

PMID- 19752015
TI  - Florida's model of nursing home Medicaid reimbursement for disaster-related
      expenses.
AB  - PURPOSE: This study describes Florida's model of Medicaid nursing home (NH)
      reimbursement to compensate NHs for disaster-related expenses incurred as a
      result of 8 hurricanes within a 2-year period. This Florida model can serve as a
      demonstration for a national model for disaster-related reimbursement. DESIGN AND
      METHODS: Florida reimburses NHs for approved disaster-related costs through
      hurricane interim rate requests (IRRs). The state developed its unique Medicaid
      per diem rate temporary add-on by adapting its standard rate-setting
      reimbursement methodology. To understand the payment mechanisms and the costs
      that facilities incurred as a result of natural disasters, we examined the IRRs
      and cost reports for facilities requesting and receiving reimbursement. RESULTS:
      Cost reports and IRR applications indicated that Florida Medicaid spent close to
      $16 million to pay for hurricane-related costs to NHs. IMPLICATIONS: Without
      Florida's Hurricane IRR program, many facilities would have not been reimbursed
      for their hurricane-related costs. Florida's model is one that Medicare and other
      states should consider adopting to ensure that NHs receive adequate reimbursement
      for disaster-related expenses, including tornadoes, earthquakes, floods,
      blizzards, and other catastrophic events.

PMID- 19752016
TI  - Microleakage under orthodontic brackets bonded with the custom base indirect
      bonding technique.
AB  - The aim of this in vitro study was to compare microleakage of orthodontic
      brackets between enamel-composite and composite-bracket interfaces at the
      occlusal and gingival margins, bonded using indirect bonding systems with that of
      a conventional direct bonding method. Forty freshly extracted human maxillary
      premolar teeth were randomly divided into two groups. In group 1, the brackets
      were bonded to teeth directly according to the manufacturer's recommendations.
      Group 2 consisted of 20 teeth bonded indirectly with Transbond XT (3M-Unitek), as
      the adhesive, and Sondhi Rapid Set A/B Primer (3M-Unitek), a filled resin primer.
      After bonding, the specimens were further sealed with nail varnish, stained with
      0.5 per cent basic fuchsine for 24 hours, sectioned and examined under a
      stereomicroscope, and scored for microleakage at the enamel-composite and
      composite-bracket interfaces from both the occlusal and gingival margins.
      Statistical analyses were performed using Kruskal-Wallis and Mann-Whitney U-tests
      with Bonferroni correction. The gingival sides of group 1 displayed a higher
      median microleakage score than the occlusal side at the enamel-composite
      interface but this was not statistically significant (P > 0.05). All occlusal
      margins in both groups showed no microleakage under orthodontic brackets at the
      enamel-composite or composite-bracket interfaces. Comparisons of the microleakage
      scores between the direct and the indirect bonding groups at the enamel-composite
      and composite-bracket interfaces indicated no statistically significant
      microleakage differences at the gingival and occlusal margins (P > 0.05). The
      type of bonding method (direct versus indirect) did not significantly affect the
      amount of microleakage at the enamel-composite-bracket complex.

PMID- 19752017
TI  - Chondroitin sulphate (WF6 epitope) levels in peri-miniscrew implant crevicular
      fluid during orthodontic loading.
AB  - The aim of this study was to monitor changes in chondroitin sulphate (CS; WF6
      epitope) levels in peri-miniscrew implant crevicular fluid (PMICF) during
      orthodontic loading. Ten patients (seven males and three females; aged 22.0 +/-
      3.4 years), who required orthodontic treatment with extraction of all four
      premolar teeth, participated in the study. Twenty miniscrew implants (used as
      orthodontic anchorage) were placed, two in each patient, buccally and bilaterally
      in the alveolar bone between the roots of the maxillary posterior teeth.
      Sentalloy closed-coil springs (50 g) were used to load the miniscrew implants and
      to move the maxillary canines distally. During the unloaded period, PMICF samples
      were collected on days 1, 3, 5, and 7 after miniscrew implant placement and on
      days 14, 21, 28, and 35 during the loaded period. Clinical mobility assessments
      of the miniscrew implants were recorded at each visit. The competitive enzyme
      linked immunosorbent assay with monoclonal antibody WF6 was used to detect CS
      (WF6 epitope) levels in the PMICF samples. The differences between the CS (WF6
      epitope) levels during the unloaded and loaded periods were determined by a Mann
      Whitney U-test. During the loaded period, two miniscrew implants were considered
      to have failed. The CS (WF6 epitope) levels during the unloaded period ranged
      from 0.00 to 758.03 ng/ml and those during the loaded period from 0.00 to 1025.11
      ng/ml. Medians of CS (WF6 epitope) levels, around 'immobile' miniscrew implants,
      between the unloaded and loaded periods were not significantly different (P =
      0.07). CS (WF6 epitope) levels in PMICF can be detected and may be used as
      biomarkers for assessing alveolar bone remodelling around miniscrew implants
      during orthodontic loading.

PMID- 19752018
TI  - Treatment and post-treatment effects of facemask therapy on the sagittal
      pharyngeal dimensions in Class III subjects.
AB  - The purpose of this cephalometric study was to analyse the treatment and post
      treatment craniofacial effects of a facemask (FM) combined with a bite block (BB)
      with specific regard to the sagittal pharyngeal dimensions in subjects with a
      Class III malocclusion when compared with an untreated Class III control group.
      The FM/BB group (22 subjects, 12 females and 10 males) had a mean age pre
      treatment (T1) of 8.9 +/- 1.5 years, at the end of active treatment (T2) of 10.5
      +/- 1.3 years, and post-treatment (T3) of 12.6 +/- 1.9 years. The treated group
      was compared with a control group of 14 subjects (6 females and 8 males) with
      untreated Class III malocclusions that matched the FM/BB group as to age at T1,
      T2, and T3, observation periods and skeletal maturation. Comparisons of the T2-T1
      and T3-T1 changes between the two groups were analysed with the Mann-Whitney
      test. Significant favourable skeletal changes in the maxilla and mandible were
      observed in the treated group both after Ts2 and T3. No significant short- or
      long-term changes in the sagittal oropharyngeal and nasopharyngeal airway
      dimensions were induced by maxillary protraction in subjects with a Class III
      malocclusion when compared with untreated controls.

PMID- 19752019
TI  - Bridging of the sella turcica in skeletal Class III subjects.
AB  - Several investigations have analysed the frequency of sella turcica anomalies in
      patients with severe craniofacial deviations. Until now, there have been no
      studies concerning the prevalence of sella turcica bridging in homogenous groups
      of patients. Therefore, the aims of this controlled study were to analyse the
      prevalence of sella turcica bridging and measure the size of the sella turcica in
      two well-defined groups of Caucasian individuals. In a multicentre retrospective
      study, 400 pre-treatment lateral cephalograms of adult patients (over 17 years of
      age) with a skeletal Class III (n = 250, 132 females and 118 males) or a skeletal
      Class I (n = 150, 94 females and 56 males) malocclusion were analysed. The
      morphology, length, depth, and diameter of the sella turcica were investigated.
      For statistical analysis, chi-square and t-tests were used. Skeletal Class III
      patients presented a significantly higher rate of sella turcica bridging, 16.8
      per cent (P = 0.031), in comparison with skeletal Class I patients, whose rate
      was 9.4 per cent. No differences between females and males were detected for the
      length, depth, and diameter of the sella turcica. Bridging of the sella turcica
      could be seen radiographically in skeletal Class III subjects.

PMID- 19752020
TI  - Entropic organization of interphase chromosomes.
AB  - Chromosomes are not distributed randomly in nuclei. Appropriate positioning can
      activate (or repress) genes by bringing them closer to active (or inactive)
      compartments like euchromatin (or heterochromatin), and this is usually assumed
      to be driven by specific local forces (e.g., involving H bonds between
      nucleosomes or between nucleosomes and the lamina). Using Monte Carlo
      simulations, we demonstrate that nonspecific (entropic) forces acting alone are
      sufficient to position and shape self-avoiding polymers within a confining sphere
      in the ways seen in nuclei. We suggest that they can drive long flexible polymers
      (representing gene-rich chromosomes) to the interior, compact/thick ones (and
      heterochromatin) to the periphery, looped (but not linear) ones into
      appropriately shaped (ellipsoidal) territories, and polymers with large terminal
      beads (representing centromeric heterochromatin) into peripheral chromocenters.
      Flexible polymers tend to intermingle less than others, which is in accord with
      observations that gene-dense (and so flexible) chromosomes make poor
      translocation partners. Thus, entropic forces probably participate in the self
      organization of chromosomes within nuclei.

PMID- 19752021
TI  - The dynamin-related GTPase Drp1 is required for embryonic and brain development
      in mice.
AB  - The dynamin-related guanosine triphosphatase Drp1 mediates the division of
      mitochondria and peroxisomes. To understand the in vivo function of Drp1,
      complete and tissue-specific mouse knockouts of Drp1 were generated. Drp1-null
      mice die by embryonic day 11.5. This embryonic lethality is not likely caused by
      gross energy deprivation, as Drp1-null cells showed normal intracellular
      adenosine triphosphate levels. In support of the role of Drp1 in organelle
      division, mitochondria formed extensive networks, and peroxisomes were elongated
      in Drp1-null embryonic fibroblasts. Brain-specific Drp1 ablation caused
      developmental defects of the cerebellum in which Purkinje cells contained few
      giant mitochondria instead of the many short tubular mitochondria observed in
      control cells. In addition, Drp1-null embryos failed to undergo developmentally
      regulated apoptosis during neural tube formation in vivo. However, Drp1-null
      embryonic fibroblasts have normal responses to apoptotic stimuli in vitro,
      suggesting that the apoptotic function of Drp1 depends on physiological cues.
      These findings clearly demonstrate the physiological importance of Drp1-mediated
      organelle division in mice.

PMID- 19752023
TI  - Iain Cheeseman: a strong attachment to kinetochores. [An interview by Ben Short].

PMID- 19752022
TI  - Regulation of dynein-driven microtubule sliding by the axonemal protein kinase
      CK1 in Chlamydomonas flagella.
AB  - Experimental analysis of isolated ciliary/flagellar axonemes has implicated the
      protein kinase casein kinase I (CK1) in regulation of dynein. To test this
      hypothesis, we developed a novel in vitro reconstitution approach using purified
      recombinant Chlamydomonas reinhardtii CK1, together with CK1-depleted axonemes
      from the paralyzed flagellar mutant pf17, which is defective in radial spokes and
      impaired in dynein-driven microtubule sliding. The CK1 inhibitors (DRB and CK1-7)
      and solubilization of CK1 restored microtubule sliding in pf17 axonemes, which is
      consistent with an inhibitory role for CK1. The phosphatase inhibitor microcystin
      LR blocked rescue of microtubule sliding, indicating that the axonemal
      phosphatases, required for rescue, were retained in the CK1-depleted axonemes.
      Reconstitution of depleted axonemes with purified, recombinant CK1 restored
      inhibition of microtubule sliding in a DRB- and CK1-7-sensitive manner. In
      contrast, a purified "kinase-dead" CK1 failed to restore inhibition. These
      results firmly establish that an axonemal CK1 regulates dynein activity and
      flagellar motility.

PMID- 19752024
TI  - Tropomodulin1 is required for membrane skeleton organization and hexagonal
      geometry of fiber cells in the mouse lens.
AB  - Hexagonal packing geometry is a hallmark of close-packed epithelial cells in
      metazoans. Here, we used fiber cells of the vertebrate eye lens as a model system
      to determine how the membrane skeleton controls hexagonal packing of post-mitotic
      cells. The membrane skeleton consists of spectrin tetramers linked to actin
      filaments (F-actin), which are capped by tropomodulin1 (Tmod1) and stabilized by
      tropomyosin (TM). In mouse lenses lacking Tmod1, initial fiber cell morphogenesis
      is normal, but fiber cell hexagonal shapes and packing geometry are not
      maintained as fiber cells mature. Absence of Tmod1 leads to decreased gammaTM
      levels, loss of F-actin from membranes, and disrupted distribution of beta2
      spectrin along fiber cell membranes. Regular interlocking membrane protrusions on
      fiber cells are replaced by irregularly spaced and misshapen protrusions. We
      conclude that Tmod1 and gammaTM regulation of F-actin stability on fiber cell
      membranes is critical for the long-range connectivity of the spectrin-actin
      network, which functions to maintain regular fiber cell hexagonal morphology and
      packing geometry.

PMID- 19752025
TI  - Coassembly of Mgm1 isoforms requires cardiolipin and mediates mitochondrial inner
      membrane fusion.
AB  - Two dynamin-related protein (DRP) families are essential for fusion of the outer
      and inner mitochondrial membranes, Fzo1 (yeast)/Mfn1/Mfn2 (mammals) and Mgm1
      (yeast)/Opa1 (mammals), respectively. Fzo1/Mfns possess two medial transmembrane
      domains, which place their critical GTPase and coiled-coil domains in the
      cytosol. In contrast, Mgm1/Opa1 are present in cells as long (l) isoforms that
      are anchored via the N terminus to the inner membrane, and short (s) isoforms
      were predicted to be soluble in the intermembrane space. We addressed the roles
      of Mgm1 isoforms and how DRPs function in membrane fusion. Our analysis indicates
      that in the absence of a membrane, l- and s-Mgm1 both exist as inactive GTPase
      monomers, but that together in trans they form a functional dimer in a
      cardiolipin-dependent manner that is the building block for higher-order
      assemblies.

PMID- 19752026
TI  - Role of ERO1-alpha-mediated stimulation of inositol 1,4,5-triphosphate receptor
      activity in endoplasmic reticulum stress-induced apoptosis.
AB  - Endoplasmic reticulum (ER) stress-induced apoptosis is involved in many diseases,
      but the mechanisms linking ER stress to apoptosis are incompletely understood.
      Based on roles for C/EPB homologous protein (CHOP) and ER calcium release in
      apoptosis, we hypothesized that apoptosis involves the activation of inositol
      1,4,5-triphosphate (IP3) receptor (IP3R) via CHOP-induced ERO1-alpha (ER oxidase
      1 alpha). In ER-stressed cells, ERO1-alpha is induced by CHOP, and small
      interfering RNA (siRNA) knockdown of ERO1-alpha suppresses apoptosis. IP3-induced
      calcium release (IICR) is increased during ER stress, and this response is
      blocked by siRNA-mediated silencing of ERO1-alpha or IP3R1 and by loss-of
      function mutations in Ero1a or Chop. Reconstitution of ERO1-alpha in Chop(-/-)
      macrophages restores ER stress-induced IICR and apoptosis. In vivo, macrophages
      from wild-type mice but not Chop(-/-) mice have elevated IICR when the animals
      are challenged with the ER stressor tunicamycin. Macrophages from insulin
      resistant ob/ob mice, another model of ER stress, also have elevated IICR. These
      data shed new light on how the CHOP pathway of apoptosis triggers calcium
      dependent apoptosis through an ERO1-alpha-IP3R pathway.

PMID- 19752027
TI  - Surface-exposed histone-like protein a modulates adherence of Streptococcus
      gallolyticus to colon adenocarcinoma cells.
AB  - Streptococcus gallolyticus (formerly known as Streptococcus bovis biotype I) is a
      low-grade opportunistic pathogen which is considered to be associated with colon
      cancer. It is thought that colon polyps or tumors are the main portal of entry
      for this bacterium and that heparan sulfate proteoglycans (HSPGs) at the colon
      tumor cell surface are involved in bacterial adherence during the first stages of
      infection. In this study, we have shown that the histone-like protein A (HlpA) of
      S. gallolyticus is a genuine anchorless bacterial surface protein that binds to
      lipoteichoic acid (LTA) of the gram-positive cell wall in a growth phase
      dependent manner. In addition, HlpA was shown to be one of the major heparin
      binding proteins of S. gallolyticus able to bind to the HSPG-expressing colon
      tumor cell lines HCT116 and HT-29. Strikingly, although wild-type levels of HlpA
      appeared to contribute to adherence, coating of additional HlpA at the bacterial
      surface resulted in reduced binding to colon tumor cells. This may be explained
      by the fact that heparan sulfate and LTA compete for the same binding site in
      HlpA. Altogether, this study implies that HlpA serves as a fine-tuning factor for
      bacterial adherence.

PMID- 19752028
TI  - Bcl-2 regulates the onset of shiga toxin 1-induced apoptosis in THP-1 cells.
AB  - Shiga toxins (Stxs), which are proteins expressed by the enteric pathogens
      Shigella dysenteriae serotype 1 and some serotypes of Escherichia coli, are
      potent protein synthesis inhibitors. Stx-producing organisms cause bloody
      diarrhea with the potential to progress to acute renal failure and central
      nervous system complications. Studies using animal models of these diseases have
      shown that Stxs are major virulence factors, and purified toxins have been shown
      to be capable of killing many types of cells in vitro. We showed that Stx type 1
      (Stx1) rapidly induced apoptosis in undifferentiated, monocytic THP-1 cells
      through a mechanism involving the endoplasmic reticulum (ER) stress response.
      Rapid apoptosis correlated with increased expression of C/EBP homologous protein
      (CHOP), TRAIL, and DR5, while expression of the antiapoptotic factor Bcl-2 was
      downregulated. Stx1 treatment of differentiated, macrophage-like THP-1 cells was
      associated with cytokine production and delayed apoptosis. The mechanisms
      contributing to cell maturation-dependent differences in responses to Stx1 are
      unknown. We show here that in macrophage-like cells, Stx1 activated the proximal
      ER stress sensors RNA-dependent protein kinase-like ER kinase and inositol
      requiring ER signal kinase 1alpha but did not activate activating transcription
      factor 6. Proapoptotic signaling pathways mediated by CHOP and by Bax and Bak
      were activated by Stx1. However, the toxin also activated prosurvival signaling
      through increased expression, mitochondrial translocation, and alternative
      phosphorylation of Bcl-2.

PMID- 19752029
TI  - Mycobacterium tuberculosis culture filtrate proteins plus CpG
      Oligodeoxynucleotides confer protection to Mycobacterium bovis BCG-primed mice by
      inhibiting interleukin-4 secretion.
AB  - Culture filtrate proteins (CFP) are potential targets for tuberculosis vaccine
      development. We previously showed that despite the high level of gamma interferon
      (IFN-gamma) production elicited by homologous immunization with CFP plus CpG
      oligodeoxynucleotides (CFP/CpG), we did not observe protection when these mice
      were challenged with Mycobacterium tuberculosis. In order to use the IFN-gamma
      inducing ability of CFP antigens, in this study we evaluated a prime-boost
      heterologous immunization based on CFP/CpG to boost Mycobacterium bovis BCG
      vaccination in order to find an immunization schedule that could induce
      protection. Heterologous BCG-CFP/CpG immunization provided significant protection
      against experimental tuberculosis, and this protection was sustained during the
      late phase of infection and was even better than that conferred by a single BCG
      immunization. The protection was associated with high levels of antigen-specific
      IFN-gamma and interleukin-17 (IL-17) and low IL-4 production. The deleterious
      role of IL-4 was confirmed when IL-4 knockout mice vaccinated with CFP/CpG showed
      consistent protection similar to that elicited by BCG-CFP/CpG heterologous
      immunization. These findings show that a single dose of CFP/CpG can represent a
      new strategy to boost the protection conferred by BCG vaccination. Moreover,
      different immunological parameters, such as IFN-gamma and IL-17 and tightly
      regulated IL-4 secretion, seem to contribute to the efficacy of this tuberculosis
      vaccine.

PMID- 19752030
TI  - Pyruvate formate lyase is required for pneumococcal fermentative metabolism and
      virulence.
AB  - Knowledge of the in vivo physiology and metabolism of Streptococcus pneumoniae is
      limited, even though pneumococci rely on efficient acquisition and metabolism of
      the host nutrients for growth and survival. Because the nutrient-limited, hypoxic
      host tissues favor mixed-acid fermentation, we studied the role of the
      pneumococcal pyruvate formate lyase (PFL), a key enzyme in mixed-acid
      fermentation, which is activated posttranslationally by PFL-activating enzyme
      (PFL-AE). Mutations were introduced to two putative pfl genes, SPD0235 and
      SPD0420, and two putative pflA genes, SPD0229 and SPD1774. End-product analysis
      showed that there was no formate, the main end product of the reaction catalyzed
      by PFL, produced by mutants defective in SPD0420 and SPD1774, indicating that
      SPD0420 codes for PFL and SPD1774 for putative PFL-AE. Expression of SPD0420 was
      elevated in galactose-containing medium in anaerobiosis compared to growth in
      glucose, and the mutation of SPD0420 resulted in the upregulation of fba and pyk,
      encoding, respectively, fructose 1,6-bisphosphate aldolase and pyruvate kinase,
      under the same conditions. In addition, an altered fatty acid composition was
      detected in SPD0420 and SPD1774 mutants. Mice infected intranasally with the
      SPD0420 and SPD1774 mutants survived significantly longer than the wild type
      infected cohort, and bacteremia developed later in the mutant cohort than in the
      wild type-infected group. Furthermore, the numbers of CFU of the SPD0420 mutant
      were lower in the nasopharynx and the lungs after intranasal infection, and fewer
      numbers of mutant CFU than of wild-type CFU were recovered from blood specimens
      after intravenous infection. The results demonstrate that there is a direct link
      between pneumococcal fermentative metabolism and virulence.

PMID- 19752031
TI  - Distinctive profiles of infection and pathology in hamsters infected with
      Clostridium difficile strains 630 and B1.
AB  - Currently, the Golden Syrian hamster is widely considered an important model of
      Clostridium difficile disease, as oral infection of this animal pretreated with
      antibiotics reproduces many of the symptoms observed in humans. Two C. difficile
      strains, B1 and 630, showed significant differences in the progression and
      severity of disease in this model. B1-infected hamsters exhibited more severe
      pathology and a shorter time to death than hamsters infected with 630.
      Histological changes in the gut did not correlate with absolute numbers of C.
      difficile bacteria, but there were clear differences in the distribution of
      bacteria within gut tissues. Light, scanning, and transmission electron
      microscopy revealed high numbers of B1 bacteria at the mucosal surface of the
      tissue, whereas 630 bacteria were more frequently associated with the crypt
      regions. Both B1 and 630 bacteria were frequently observed within
      polymorphonuclear leukocytes, although, interestingly, a space frequently
      separated B1 bacteria from the phagosome wall, a phenomenon not observed with
      630. However, pilus-like structures were detected on 630 located in the crypts of
      the gut tissue. Furthermore, B1 bacteria, but not 630 bacteria, were found within
      nonphagocytic cells, including enterocytes and muscle cells.

PMID- 19752032
TI  - Helminth infection can reduce insulitis and type 1 diabetes through CD25- and IL
      10-independent mechanisms.
AB  - Parasitic helminth infection has been shown to modulate pathological inflammatory
      responses in allergy and autoimmune disease. The aim of this study was to examine
      the effects of infection with a helminth parasite, Heligmosomoides polygyrus, on
      type 1 diabetes (T1D) in nonobese diabetic (NOD) mice and to elucidate the
      mechanisms involved in this protection. H. polygyrus inoculation at 5 weeks of
      age protected NOD mice from T1D until 40 weeks of age and also inhibited the more
      aggressive cyclophosphamide-induced T1D. Moreover, H. polygyrus inoculation as
      late as 12 weeks of age reduced the onset of T1D in NOD mice. Following H.
      polygyrus inoculation of NOD mice, pancreatic insulitis was markedly inhibited.
      Interleukin-4 (IL-4), IL-10, and IL-13 expression and the frequency of CD4(+)
      CD25(+) FoxP3(+) regulatory T cells were elevated in mesenteric and pancreatic
      lymph nodes. Depletion of CD4(+) CD25(+) T cells in vivo did not abrogate H.
      polygyrus-induced T1D protection, nor did anti-IL-10 receptor blocking antibody.
      These findings suggest that infection with H. polygyrus significantly inhibits
      T1D in NOD mice through CD25- and IL-10-independent mechanisms and also reduces
      the severity of T1D when administered late after the onset of insulitis.

PMID- 19752033
TI  - Role for the Burkholderia pseudomallei capsular polysaccharide encoded by the wcb
      operon in acute disseminated melioidosis.
AB  - The capsular polysaccharide of Burkholderia pseudomallei is an essential
      virulence determinant that is required for protection from host serum cidal
      activity and opsonophagocytosis. In this study, the immune response directed
      against a B. pseudomallei capsule mutant (JW270) was investigated in an acute
      respiratory murine model. JW270 was significantly attenuated in this model (
      approximately 2 logs) to levels resembling those of avirulent Burkholderia
      thailandensis. At lethal doses, JW270 colonized the lung, liver, and spleen at
      levels similar to the wild-type strain levels and was found to trigger reduced
      pathology in the liver and spleen. Several cytokine responses were altered in
      these tissues, and importantly, the levels of gamma interferon were reduced in
      the livers and spleens of JW270-infected mice but not in the lungs. These results
      suggest that the capsular polysaccharide of B. pseudomallei is a critical
      virulence determinant in respiratory tract infections and that it is an important
      antigen for generating the Th1 immune response commonly observed in systemic
      melioidosis. Furthermore, the data suggest that host recognition of B.
      pseudomallei capsular polysaccharide in the lungs may not be as important to the
      disease outcome as the innate immune response in the peripheral organs.

PMID- 19752034
TI  - A naturally occurring Rgg variant in serotype M3 Streptococcus pyogenes does not
      activate speB expression due to altered specificity of DNA binding.
AB  - The transcriptional regulator Rgg of Streptococcus pyogenes is essential for
      expression of the secreted cysteine protease SpeB. Although all isolates of S.
      pyogenes possess the speB gene, not all of them produce the protein in vitro. In
      a murine model of infection, the absence of SpeB production is associated with
      invasive disease. We speculated that naturally occurring mutations in rgg, which
      would also abrogate SpeB production, may be present in invasive isolates of S.
      pyogenes. Examination of the inferred Rgg sequences available in public databases
      revealed that the rgg gene in strain MGAS315 (a serotype M3 strain associated
      with invasive disease) encodes a proline at amino acid position 103 (Rgg(103P));
      in contrast, all other strains encode a serine at this position (Rgg(103S)). A
      caseinolytic assay and Western blotting indicated that strain MGAS315 does not
      produce SpeB in vitro. Gene-swapping experiments showed that the rgg gene of
      MGAS315 is solely responsible for the lack of SpeB expression. In contrast to
      Rgg(103S), Rgg(103P) does not bind to the speB promoter in gel shift assays,
      which correlates with a lack of speB expression. Despite its inability to
      activate speB expression, Rgg(103P) retains the ability to bind to DNA upstream
      of norA and to influence its expression. Overall, this study illustrates how
      variation at the rgg locus may contribute to the phenotypic diversity of S.
      pyogenes.

PMID- 19752035
TI  - Malaria ookinete surface protein-based vaccination via the intranasal route
      completely blocks parasite transmission in both passive and active vaccination
      regimens in a rodent model of malaria infection.
AB  - Malaria vaccines based on ookinete surface proteins (OSPs) of the malaria
      parasites block oocyst development in feeding mosquitoes and hence disrupt the
      parasite life cycle and prevent the disease from being transmitted to other
      individuals. To investigate whether a noninvasive mucosal vaccination regimen
      effectively blocks parasite transmission in vivo, Plasmodium yoelii Pys25, a
      homolog of the Pfs25 and Pvs25 OSPs of Plasmodium falciparum and Plasmodium
      vivax, respectively, was intranasally (i.n.) administered using a complement
      deficient DBA/2 mouse malaria infection model, in which a highly elevated level
      of oocysts develops in feeding mosquitoes. Vaccinated mice developed a robust
      antibody response when the vaccine antigen was given together with cholera toxin
      adjuvant. The induced immune serum was passively transferred to DBA/2 mice 3 days
      after infection with P. yoelii 17XL, and Anopheles stephensi mosquitoes were
      allowed to feed on the infected mice before or after serum transfusion. This
      passive immunization completely blocked oocyst development; however, immune serum
      induced by the antigen or adjuvant alone did not have such a profound
      antiparasite effect. Further, when i.n. vaccinated mice were infected with the
      parasite and then mosquitoes were allowed to directly feed on the infected mice,
      complete blockage of transmission was again observed. To our knowledge, this is
      the first time that mucosal vaccination has been demonstrated to be efficacious
      for directly preventing parasite transmission from vaccinated animals to
      mosquitoes, and the results may provide important insight into rational design of
      nonparenteral vaccines for use against human malaria.

PMID- 19752036
TI  - Th2 but not Th1 immune bias results in altered lung functions in a murine model
      of pulmonary Cryptococcus neoformans infection.
AB  - Changes in airway dynamics have been reported in the rat model of pulmonary
      cryptococcosis. However, it is not known if Cryptococcus neoformans-induced
      changes in lung functions are related to the immunophenotype that develops in
      response to cryptococcal infection in the lungs. In this study we performed a
      parallel analysis of the immunophenotype and airway resistance (standard
      resistance of the airways [SRAW]) in BALB/c mice infected with highly virulent C.
      neoformans strain H99 and moderately virulent strain 52D. H99 infection evoked a
      Th2 response and was associated with increased SRAW, while the SRAW for 52D
      infection, which resulted in a predominantly Th1-skewed response, did not differ
      from the SRAW for uninfected mice. We found that an altered SRAW in mice did not
      positively or negatively correlate with the pulmonary fungal burden, the
      magnitude of inflammatory response, the numbers of T cells, eosinophils or
      eosinophil subsets, neutrophils, or monocytes/macrophages, or the levels of
      cytokines (interleukin-4 [IL-4], IL-10, gamma interferon, or IL-13) produced by
      lung leukocytes. However, the level of a systemic Th2 marker, serum
      immunoglobulin E (IgE), correlated significantly with SRAW, indicating that the
      changes in lung functions were proportional to the level of Th2 skewing in this
      model. These data also imply that IgE may contribute to the altered SRAW observed
      in H99-infected mice. Lung histological analysis revealed severe allergic
      bronchopulmonary mycosis pathology in H99-infected mice and evidence of
      protective responses in 52D-infected mice with well-marginalized lesions. Taken
      together, the data show that C. neoformans can significantly affect airflow
      physiology, particularly in the context of a Th2 immune response with possible
      involvement of IgE as an important factor.

PMID- 19752037
TI  - Frequencies of region of difference 1 antigen-specific but not purified protein
      derivative-specific gamma interferon-secreting T cells correlate with the
      presence of tuberculosis disease but do not distinguish recent from remote latent
      infections.
AB  - The majority of individuals infected with Mycobacterium tuberculosis achieve
      lifelong immune containment of the bacillus. What constitutes this effective host
      immune response is poorly understood. We compared the frequencies of gamma
      interferon (IFN-gamma)-secreting T cells specific for five region of difference 1
      (RD1)-encoded antigens and one DosR-encoded antigen in 205 individuals either
      with active disease (n = 167), whose immune responses had failed to contain the
      bacillus, or with remotely acquired latent infection (n = 38), who had
      successfully achieved immune control, and a further 149 individuals with recently
      acquired asymptomatic infection. When subjects with an IFN-gamma enzyme-linked
      immunospot (ELISpot) assay response to one or more RD1-encoded antigens were
      analyzed, T cells from subjects with active disease recognized more pools of
      peptides from these antigens than T cells from subjects with nonrecent latent
      infection (P = 0.002). The T-cell frequencies for peptide pools were greater for
      subjects with active infection than for subjects with nonrecent latent infection
      for summed RD1 peptide pools (P <or= 0.006) and culture filtrate protein 10 (CFP
      10) antigen (P = 0.029). Individuals with recently acquired (<6 months) versus
      remotely acquired (>6 months) latent infection did not differ in numbers of
      peptide pools recognized, proportions recognizing any individual antigen or
      peptide pool, or antigen-specific T-cell frequencies (P >or= 0.11). The hierarchy
      of immunodominance for different antigens was purified protein derivative (PPD) >
      CFP-10 > early secretory antigenic target 6 > Rv3879c > Rv3878 > Rv3873 > Acr1,
      and the hierarchies were very similar for active and remotely acquired latent
      infections. Responses to the DosR antigen alpha-crystallin were not associated
      with latency (P = 0.373). In contrast to the RD1-specific responses, the
      responses to PPD were not associated with clinical status (P > 0.17) but were
      strongly associated with positive tuberculin skin test results (>or=15-mm
      induration; P <or= 0.01). Our results suggest that RD1-specific IFN-gamma
      secreting T-cell frequencies correlate with the presence of disease rather than
      with protective immunity in M. tuberculosis-infected individuals and do not
      distinguish recently acquired asymptomatic infection from remotely acquired
      latent infection.

PMID- 19752038
TI  - Tele-ICU: experience to date.
AB  - Tele-intensive care unit (ICU) is a care provided to critically ill patients by
      off-site clinicians using audio, video, and electronic links to leverage
      technical, informational, and clinical resources. Providing care includes the
      ability to detect patient's instability or laboratory abnormalities in real-time,
      collect additional clinical information from or about the patient, order
      diagnostic testing, make diagnoses, implement treatment, render other forms of
      intensive care such as managing life-support devices, and communicate with
      patients and bedside providers. This review summarizes how tele-ICU services are
      delivered, the alternative approaches that have been used, and summarizes
      published reports of its effects on patient-focused outcomes. Tele-ICU is thought
      to have great promise to support critically ill adults.

PMID- 19752039
TI  - Lipoprotein (a) levels in childhood arterial ischemic stroke.
AB  - Lipoprotein (a) is a cholesterol-rich plasma lipoprotein with a lipid composition
      similar to that of low-density lipoproteins (LDL). Many prospective and case
      control studies identified elevated levels of lipoprotein (a) as a risk factor
      for premature myocardial infarction and stroke. Elevated lipoprotein (a) has been
      identified as a genetically determined risk factor for stroke in young adults,
      but only preliminary data are available on its role as a risk factor for ischemic
      stroke in infants and children.Fifty two children with arterial ischemic stroke
      and 78 age- and sex-matched healthy children were studied. Data of this study
      indicate that 26.9% of children with arterial ischemic stroke had high
      lipoprotein (a) levels in comparison with the age matched healthy control
      group.Measurement of lipoprotein (a) should be included in screening programs
      performed in young patients suffering not only from venous thromboembolism but
      also arterial ischemic stroke, in addition to other thrombophilic factors.

PMID- 19752040
TI  - m-Calpain antagonizes RhoA overactivation and endothelial barrier dysfunction
      under disturbed shear conditions.
AB  - AIMS: It has been reported that laminar shear flow (LF) improves barrier
      functions in vascular endothelial cells (ECs), whereas disturbed flow (DF)
      impairs the barrier. Our previous study showed that LF stimulus led to the
      activation of the cysteine protease, m-calpain, in ECs, which can influence RhoA
      activity. We hypothesized that m-calpain participates in the shear pattern
      dependent EC barrier maintenance through RhoA signalling. METHODS AND RESULTS: m
      Calpain expression levels in the intima in the inferior aspect of mouse aortic
      arch where DF dominates were higher than those in adjacent regions. Elevation in
      transendothelial albumin permeability, which was induced by administration of a
      calpain inhibitor (ALLM), was prominent in the inferior arch; moreover, this
      elevation was abolished by Rho kinase (ROCK) inhibitor (Y-27632). Similarly,
      short interfering RNA (siRNA)-induced silencing of m-calpain resulted in
      increased RhoA activity and hyperpermeability in the aortic arch, which was
      accompanied by ROCK inhibitor-sensitive phosphorylation of downstream effecter
      LIM kinase 2 (LIMK2), stress fibre accumulation in endothelium and enhanced
      interendothelial gaps. Exposure of human umbilical vein endothelial cells to LF
      diminished RhoA activity; in contrast, DF facilitated the activity. siRNA-induced
      m-calpain silencing further accelerated the DF-induced RhoA overactivation,
      phosphorylation of LIMK2, and cytoskeletal rearrangement, resulting in barrier
      dysfunction in the cells. CONCLUSION: Our findings revealed relatively high m
      calpain expression levels in the inferior arch. The m-calpain activity
      antagonizes DF-induced overactivation of RhoA/ROCK/LIMK2 signalling and
      subsequent cytoskeletal rearrangement in ECs, which leads to barrier improvement.

PMID- 19752041
TI  - Percutaneous aortic valve replacement: an important advance in cardiology.

PMID- 19752043
TI  - Non-coding regulatory regions in genomes. Editorial.

PMID- 19752044
TI  - Pan-vertebrate conserved non-coding sequences associated with developmental
      regulation.
AB  - Whilst coding sequences are readily recognised in vertebrate genomes using
      computational approaches, the identification of non-coding regulatory sequences
      has traditionally been much more difficult, due to their small size and, as a
      general rule, low sequence homology between genomes. Nevertheless, a small
      proportion of non-coding sequence is very highly conserved across the entire
      vertebrate radiation. This review will look at the specific properties of these
      sequences, how they have been identified and assayed functionally, and current
      progress in the quest to identify and understand the underlying language and
      grammar encoded within them. I will also discuss the evolution of these elements,
      and examine their emerging and likely roles in disease. Together these analyses
      are starting to unravel how conserved non-coding regions function at the
      molecular level.

PMID- 19752045
TI  - Chromatin insulators: lessons from the fly.
AB  - Chromatin insulators are DNA-protein complexes with broad functions in nuclear
      biology. Drosophila has at least five different types of insulators; recent
      results suggest that these different insulators share some components that may
      allow them to function through common mechanisms. Data from genome-wide
      localization studies of insulator proteins indicate a possible functional
      specialization, with different insulators playing distinct roles in nuclear
      biology. Cells have developed mechanisms to control insulator activity by
      recruiting specialized proteins or by covalent modification of core components.
      Current results suggest that insulators set up cell-specific blueprints of
      nuclear organization that may contribute to the establishment of different
      patterns of gene expression during cell differentiation and development.

PMID- 19752046
TI  - Boundaries in vertebrate genomes: different solutions to adequately insulate gene
      expression domains.
AB  - Gene expression domains are normally not arranged in vertebrate genomes according
      to their expression patterns. Instead, it is not unusual to find genes expressed
      in different cell types, or in different developmental stages, sharing a
      particular region of a chromosome. Therefore, the existence of boundaries, or
      insulators, as non-coding gene regulatory elements, is instrumental for the
      adequate organization and function of vertebrate genomes. Through the evolution
      and natural selection at the molecular level, and according to available DNA
      sequences surrounding a locus, previously existing or recently mobilized,
      different elements have been recruited to serve as boundaries, depending on their
      suitability to properly insulate gene expression domains. In this regard, several
      gene regulatory elements, including scaffold/matrix-attachment regions, members
      of families of DNA repetitive elements (such as LINEs or SINEs), target sites for
      the zinc-finger multipurpose nuclear factor CTCF, enhancers and locus control
      regions, have been reported to show functional activities as insulators. In this
      review, we will address how such a variety of apparently different genomic
      sequences converge in a similar function, namely, to adequately insulate a gene
      expression domain, thereby allowing the locus to be expressed according to their
      own gene regulatory elements without interfering itself and being interfered by
      surrounding loci. The identification and characterization of genomic boundaries
      is not only interesting as a theoretical exercise for better understanding how
      vertebrate genomes are organized, but also allows devising new and improved gene
      transfer strategies to ensure the expression of heterologous DNA constructs in
      ectopic genomic locations.

PMID- 19752047
TI  - Inhibin and premature ovarian failure.
AB  - BACKGROUND: Elucidation of the causes of premature ovarian failure (POF) is
      difficult due to the heterogeneity of the condition. Inhibin is a potential
      candidate gene for POF based on its dual actions on FSH secretion by the
      pituitary and gametogenesis in the gonads. A missense mutation in the inhibin
      alpha subunit gene (INHA G769A) is associated with POF in several populations.
      However, there is phenotypic heterogeneity in INHA G769A mutation carriers.
      METHODS: Relevant studies were identified by searching PubMed and mutational
      frequencies combined for meta-analysis. RESULTS: Meta-analysis of published
      studies revealed a risk difference of 0.04 (-0.030 to 0.11). The occurrence of
      asymptomatic carriers in populations suggests incomplete penetrance and/or a
      multi-genetic cause of POF. We propose that a decline in inhibin bioactivity
      caused by the mutation could increase FSH levels; and in a susceptible
      individual, the heightened sensitivity to gonadotrophins causes POF. Impaired
      paracrine effects of inhibin could impact folliculogenesis due to reduced
      antagonism of activin, bone morphogenetic protein 15 and growth differentiation
      factor 9. Functional studies of this mutation indicate normal production of
      dimeric inhibin A and B and impaired bioactivity of inhibin B. CONCLUSIONS: The
      identification of an autosomal mutation in the inhibin alpha subunit gene that is
      significantly linked to POF in certain ethnic populations highlights the role of
      inhibin in the regulation of ovarian biology and fertility. Although the
      reduction of inhibin B bioactivity by the INHA G769A mutation is clearly not the
      only cause, evidence suggests that this change may serve as a susceptibility
      factor, increasing the likelihood of POF.

PMID- 19752048
TI  - Transcriptomic profiling of heat-stress response in potato periderm.
AB  - Potato (Solanum tuberosum L.) periderm is composed of the meristematic phellogen
      that gives rise to an external layer of suberized phellem cells (the skin) and
      the internal parenchyma-like phelloderm. The continuous addition of new skin
      layers and the sloughing of old surface layers during tuber maturation results in
      smooth, shiny skin. However, smooth-skin varieties frequently develop unsightly
      russeting in response to high soil temperatures. Microscopic observation of
      microtubers exposed to high temperatures (37 degrees C) suggested heat-enhanced
      development and accumulation of suberized skin-cell layers. To identify the genes
      involved in the periderm response to heat stress, skin and phelloderm samples
      collected separately from immature tubers exposed to high soil temperatures (33
      degrees C) and controls were subjected to transcriptome profiling using a potato
      cDNA array. As expected, the major functional group that was differentially
      expressed in both skin and phelloderm consisted of stress-related genes; however,
      while the major up-regulated phelloderm genes coded for heat-shock proteins, many
      of the skin's most up-regulated sequences were similar to genes involved in the
      development of protective/symbiotic membranes during plant-microbe interactions.
      The primary activities regulated by differentially expressed peridermal
      transcription factors were response to stress (33%) and cell proliferation and
      differentiation (28%), possibly reflecting the major processes occurring in the
      heat-treated periderm and implying the integrated activity of the stress response
      and tissue development. Accumulating data suggest that the periderm, a defensive
      tissue, responds to heat stress by enhancing the production and accumulation of
      periderm/skin layers to create a thick protective cover. Skin russeting may be an
      indirect outcome; upon continued expansion of the tuber, the inflexible skin
      cracks while new layers are produced below it, resulting in a rough skin texture.

PMID- 19752049
TI  - Symbolism of plants: examples from European-Mediterranean culture presented with
      biology and history of art: DECEMBER: cross-roses and rose crosses.

PMID- 19752050
TI  - Herpes zoster ophthalmicus. Don't forget HIV.

PMID- 19752051
TI  - Hospitals and bottling factories. Improving quality of care.

PMID- 19752052
TI  - Assisted dying debate. Life is a terminal condition.

PMID- 19752053
TI  - End of life decisions. Doctors can be trusted.

PMID- 19752055
TI  - End of life decisions. Counting end of life decisions.

PMID- 19752058
TI  - Life and Death. No power for the people.

PMID- 19752061
TI  - Osteoarthritis of the knee. Precise diagnosis and treatment.

PMID- 19752063
TI  - Minimally disruptive medicine. "Epidemic" of chronic disease?

PMID- 19752066
TI  - A/H1N1 flu pandemic. Should flu have at least one respiratory symptom?

PMID- 19752067
TI  - A/H1N1 flu pandemic. Roche responds.

PMID- 19752068
TI  - Assisted dying debate. Doctors, steer entirely clear.

PMID- 19752069
TI  - Assisted dying debate. Doctors' attitudes surveyed.

PMID- 19752070
TI  - Assisted dying debate. A baroness replies.

PMID- 19752072
TI  - Course of flu epidemic is hard to predict, says UK government adviser.

PMID- 19752075
TI  - China gears up for swine flu vaccination as virus spreads inland.

PMID- 19752076
TI  - Dimenhydrinate in children with infectious gastroenteritis: a prospective, RCT.
AB  - OBJECTIVE: Vomiting is a common symptom in children with infectious
      gastroenteritis. It contributes to fluid loss and is a limiting factor for oral
      rehydration therapy. Dimenhydrinate has traditionally been used for children with
      gastroenteritis in countries such as Canada and Germany. We investigated the
      efficacy and safety of dimenhydrinate in children with acute gastroenteritis.
      METHODS: We performed a prospective, randomized, placebo-controlled, multicenter
      trial. We randomly assigned 243 children with presumed gastroenteritis and
      vomiting to rectal dimenhydrinate or placebo. Children with no or mild
      dehydration were included. All children received oral rehydration therapy.
      Primary outcome was defined as weight gain within 18 to 24 hours after
      randomization. Secondary outcomes were number of vomiting episodes, fluid intake,
      parents' assessment of well-being, number of diarrheal episodes, and admission
      rate to hospital. We recorded potential adverse effects. RESULTS: Change of
      weight did not differ between children who received dimenhydrinate or placebo.
      The mean number of vomiting episodes between randomization and follow-up visit
      was 0.64 in the dimenhydrinate group and 1.36 in the placebo group. In total,
      69.6% of the children in the dimenhydrinate group versus 47.4% in the placebo
      group were free of vomiting between randomization and the follow-up visit.
      Hospital admission rate, fluid intake, general well-being of the children, and
      potential adverse effects, including the number of diarrhea episodes, were
      similar in both groups. CONCLUSIONS: Dimenhydrinate reduces the frequency of
      vomiting in children with mild dehydration; however, the overall benefit is low,
      because it does not improve oral rehydration and clinical outcome.

PMID- 19752077
TI  - Sugar-coaters and straight talkers: communicating about developmental delays in
      primary care.
AB  - OBJECTIVES: The goals were to investigate parents' and early intervention (EI)
      specialists' beliefs and experiences regarding discussing child development in
      primary care and to identify communication barriers and opportunities. METHODS:
      Focus groups were held with (1) mothers of young children with typical
      development, (2) mothers of young children who received EI services, and (3) EI
      specialists. Seven groups (N = 46 participants) were conducted in the greater
      Cleveland, Ohio, area. Meetings were audio-recorded, transcribed, coded, and
      analyzed, to identify themes. RESULTS: Most mothers reported a preference for a
      nonalarmist style of communication when developmental delays are suspected. In
      contrast, some mothers preferred a more direct style, including the use of labels
      to help them understand their child's development. The importance of preparation
      to accept information about developmental delays emerged as a theme in all
      groups. Elements contributing to preparedness included information about expected
      developmental skills, suggestions for promoting skills, and a specific time frame
      for follow-up evaluation. Mothers of children with disabilities perceived that
      early reassurance of normalcy by providers in response to their concerns led to
      self-doubt and increased difficulty accepting the diagnosis. CONCLUSIONS: Mothers
      and EI specialists have clear ideas about factors that promote or impede
      communication regarding child development. This information can inform primary
      care providers' approaches to monitoring and screening the development of young
      children and to communicating with parents regarding suspected developmental
      delays.

PMID- 19752078
TI  - Impact of chlorinated swimming pool attendance on the respiratory health of
      adolescents.
AB  - OBJECTIVE: The goal was to estimate the burden of allergic diseases associated
      with chlorinated pool exposure among adolescents. METHODS: We examined 847
      students, 13 to 18 years of age, who had attended outdoor or indoor chlorinated
      pools at various rates. Of them, 114 had attended mainly a copper-silver pool and
      served as a reference group. We measured total and aeroallergen-specific
      immunoglobulin E (IgE) levels in serum and screened for exercise-induced
      bronchoconstriction. Outcomes were respiratory symptoms, hay fever, allergic
      rhinitis, and asthma that had been diagnosed at any time (ever asthma) or was
      being treated with medication and/or was associated with exercise-induced
      bronchoconstriction (current asthma). RESULTS: Among adolescents with atopy with
      serum IgE levels of>30 kIU/L or aeroallergen-specific IgE, the odds ratios (ORs)
      for asthma symptoms and for ever or current asthma increased with the lifetime
      number of hours spent in chlorinated pools, reaching values of 7.1 to 14.9 when
      chlorinated pool attendance exceeded 1000 hours. Adolescents with atopy with
      chlorinated pool attendance of >100 hours had greater risk of hay fever (OR: 3.3
      6.6), and those with attendance of >1000 hours had greater risk of allergic
      rhinitis (OR: 2.2-3.5). Such associations were not found among adolescents
      without atopy or with copper-silver pool attendance. The population attributable
      risks for chlorinated pool-related ever-diagnosed asthma, hay fever, and allergic
      rhinitis were 63.4%, 62.1%, and 35.0%, respectively. CONCLUSION: Chlorinated pool
      exposure exerts an adjuvant effect on atopy that seems to contribute
      significantly to the burden of asthma and respiratory allergies among
      adolescents.

PMID- 19752079
TI  - Impact of changes in serum sodium levels on 2-year neurologic outcomes for very
      preterm neonates.
AB  - OBJECTIVE: The goal was to analyze the relationship between changes in serum
      sodium levels during the first month of life and impaired functional outcomes at
      2 years of age for very preterm infants. METHODS: All very preterm infants who
      were born at <33 weeks of gestation between January 1, 2003, and July 31, 2004,
      were hospitalized in the NICU, and survived to discharge were included in this
      study. Changes in serum sodium levels were measured, and infants were evaluated
      at corrected age of 2 years. RESULTS: The analysis involved 237 patients, for
      whom 3927 serum sodium determinations were performed during the first month of
      life. We defined 3 tertiles of changes in serum sodium levels. A total of 84
      infants demonstrated small changes in serum sodium levels (<8 mEq/ L), 86
      demonstrated large changes (8 -13 mEq/L), and 67 demonstrated very large changes
      (13 mEq/L). The reference group was represented by the first tertile. At 2 years
      of age, large and very large changes in serum sodium levels were significantly
      associated with risk of impaired functional outcomes, after adjustment for
      gestational age and perinatal and neonatal hospitalization characteristics (large
      changes: odds ratio: 3.5 [95% confidence interval: 1.1-11.8]; P = .04; very large
      changes: odds ratio: 5.1 [95% confidence interval: 1.3-13.6]; P = .02).
      CONCLUSIONS: Although large and very large changes in serum sodium levels may
      simply reflect the severity of illness and/or the quality of care, a causal
      relationship with outcomes cannot be excluded. Cautious fluid and electrolyte
      management is recommended for very premature infants.

PMID- 19752080
TI  - A scoring system for early prognostic assessment after neonatal seizures.
AB  - OBJECTIVE: The aim of this study was to devise a scoring system that could aid in
      predicting neurologic outcome at the onset of neonatal seizures. METHODS: A total
      of 106 newborns who had neonatal seizures and were consecutively admitted to the
      NICU of the University of Parma from January 1999 through December 2004 were
      prospectively followed-up, and neurologic outcome was assessed at 24 months'
      postconceptional age. We conducted a retrospective analysis on this cohort to
      identify variables that were significantly related to adverse outcome and to
      develop a scoring system that could provide early prognostic indications.
      RESULTS: A total of 70 (66%) of 106 infants had an adverse neurologic outcome.
      Six variables were identified as the most important independent risk factors for
      adverse outcome and were used to construct a scoring system: birth weight, Apgar
      score at 1 minute, neurologic examination at seizure onset, cerebral ultrasound,
      efficacy of anticonvulsant therapy, and presence of neonatal status epilepticus.
      Each variable was scored from 0 to 3 to represent the range from "normal" to
      "severely abnormal." A total composite score was computed by addition of the raw
      scores of the 6 variables. This score ranged from 0 to 12. A cutoff score of > or
      =4 provided the greatest sensitivity and specificity. CONCLUSIONS: This scoring
      system may offer an easy, rapid, and reliable prognostic indicator of neurologic
      outcome after the onset of neonatal seizures. A final assessment of the validity
      of this score in routine clinical practice will require independent validation in
      other centers.

PMID- 19752081
TI  - Ethics and professionalism in the pediatric curriculum: a survey of pediatric
      program directors.
AB  - OBJECTIVE: Since 1982, pediatric residency programs have been asked to evaluate
      trainees for ethical behavior. In 2007, the Accreditation Council for Graduate
      Medical Education required documenting teaching and evaluation of
      professionalism. Pediatric residency program directors were surveyed to ascertain
      what they know about the content and process of their ethics and professionalism
      curricula. METHODS: From February to May 2008, 394 program directors from the
      Association of Pediatric Program Directors were surveyed. RESULTS: Of 386
      eligible survey respondents, 233 (60%) returned partial or complete surveys.
      Programs were evenly divided on whether ethics was taught as an organized
      curriculum or integrated. Professionalism was combined with the ethics curriculum
      in 27% of programs and taught independently in 38% of programs, but 35% had no
      professionalism curriculum. More than one third of the respondents did not answer
      each content and structure question. Approximately two thirds of those who
      responded stated that their program dedicated <10 hours per year to ethics and
      professionalism, respectively. Nearly three fourth of programs identified
      crowding of the curriculum and one third identified lack of faculty expertise as
      curricular constraints. Respondents expressed interest in more curricular
      materials from the American Board of Pediatrics or Association of Pediatric
      Program Directors. CONCLUSIONS: Despite requirements to train and evaluate
      residents in ethics and professionalism, there is a lack of structured
      curriculum, faculty expertise, and evaluation methodology. Effectiveness of
      training curricula and evaluation tools need to be assessed if the Accreditation
      Council for Graduate Medical Education requirements for competencies in these
      areas are to be meaningfully realized.

PMID- 19752082
TI  - Closing the quality gap: promoting evidence-based breastfeeding care in the
      hospital.
AB  - Evidence shows that hospital-based practices affect breastfeeding duration and
      exclusivity throughout the first year of life. However, a 2007 CDC survey of US
      maternity facilities documented poor adherence with evidence-based practice. Of a
      possible score of 100 points, the average hospital scored only 63 with great
      regional disparities. Inappropriate provision and promotion of infant formula
      were common, despite evidence that such practices reduce breastfeeding success.
      Twenty-four percent of facilities reported regularly giving non-breast milk
      supplements to more than half of all healthy, full-term infants. Metrics
      available for measuring quality of breastfeeding care, range from comprehensive
      Baby-Friendly Hospital Certification to compliance with individual steps such as
      the rate of in-hospital exclusive breastfeeding. Other approaches to improving
      quality of breastfeeding care include (1) education of hospital decision-makers
      (eg, through publications, seminars, professional organization statements,
      benchmark reports to hospitals, and national grassroots campaigns), (2)
      recognition of excellence, such as through Baby-Friendly hospital designation,
      (3) oversight by accrediting organizations such as the Joint Commission or state
      hospital authorities, (4) public reporting of indicators of the quality of
      breastfeeding care, (5) pay-for-performance incentives, in which Medicaid or
      other third-party payers provide additional financial compensation to individual
      hospitals that meet certain quality standards, and (6) regional collaboratives,
      in which staff from different hospitals work together to learn from each other
      and meet quality improvement goals at their home institutions. Such efforts, as
      well as strong central leadership, could affect both initiation and duration of
      breastfeeding, with substantial, lasting benefits for maternal and child health.

PMID- 19752083
TI  - Increased prevalence of renal and urinary tract anomalies in children with Down
      syndrome.
AB  - OBJECTIVE: The goal was to investigate the prevalence of renal and urinary tract
      anomalies (RUTAs) in a Down syndrome (DS) population. METHODS: Data were obtained
      from the New York State Congenital Malformation Registry (NYS-CMR) in this
      retrospective cohort study. The occurrence of RUTAs was assessed for children
      with and without DS who were born in NYS between 1992 and 2004. Odds ratios (ORs)
      with 95% confidence intervals (CIs) were calculated for each malformation.
      RESULTS: Between 1992 and 2004, 3832 children with DS and 3 411 833 without DS
      were born in NYS. The prevalence of RUTAs in the DS population was 3.2%, compared
      with 0.7% in the NYS population (OR: 4.5 [95% CI: 3.8 -5.4]). Children with DS
      had significantly increased risks of anterior urethral obstruction (OR: 29.7 [95%
      CI: 4.0 -217.7]), cystic dysplastic kidney (OR: 4.5 [95% CI: 1.5-14.1]),
      hydronephrosis (OR: 8.7 [95% CI: 6.8 -11.0]), hydroureter (OR: 8.5 [95% CI: 3.5
      20.4]), hypospadias (OR: 2.0 [95% CI: 1.4 -2.9]), posterior urethral valves (OR:
      7.1 [95% CI: 1.8 -28.8]), prune belly syndrome (OR: 11.9 [95% CI: 1.6 - 85.4]),
      and renal agenesis (OR: 5.4 [95% CI: 2.8 -10.4]). There was no significantly
      increased risk of ectopic kidney (OR: 1.6 [95% CI: 0.2-11.2]) or ureteropelvic
      junction obstruction (OR: 1.4 [95% CI: 0.2-9.9]) in the DS population.
      CONCLUSION: Children with DS have significantly increased risks of RUTAs.

PMID- 19752084
TI  - Implementation of and barriers to routine HIV screening for adolescents.
AB  - OBJECTIVES: We developed and implemented a process for routine HIV screening, and
      we report screening practices and acceptance among adolescents at a large, urban,
      pediatric emergency department (ED). METHODS: We surveyed health care providers
      regarding their knowledge and beliefs about HIV and generated a protocol for
      routine HIV screening. Free, routine, opt-out, HIV screening was offered for all
      adolescents (13-18 years of age) presenting for care in the ED. We studied ED HIV
      screening rates, rates of test acceptance among patients/ guardians, patients'
      reasons for opting out, and HIV prevalence. A computerized prompt in the
      electronic chart was introduced 5 months after initiation, to address low
      screening rates. RESULTS: Of the 118 health care providers who responded to the
      preimplementation survey, 78% were unaware of the revised HIV testing guidelines
      and 58% predicted that routine screening would fail because of patient or
      guardian refusal. Of the 5399 patients who qualified for routine screening, 37%
      (2002) were offered opt-out screening. Of those, 13% opted out. Patients offered
      screening were more likely than patients not offered screening to be older (> or
      =15 years; P.002), female (P=.003), and nonwhite (P=.006). Older patients (> or
      =15 years of age) who were approached for screening were less likely to opt out
      (P=.002). Computerized prompting improved screening rates. One of the 1735 tests
      (0.57 per 1000 tests) performed yielded positive results for HIV. CONCLUSION:
      Adolescents and their guardians accept routine, optout, HIV screening, regardless
      of gender or race, and a computerized reminder enhances screening.

PMID- 19752085
TI  - Metformin selectively targets cancer stem cells, and acts together with
      chemotherapy to block tumor growth and prolong remission.
AB  - The cancer stem cell hypothesis suggests that, unlike most cancer cells within a
      tumor, cancer stem cells resist chemotherapeutic drugs and can regenerate the
      various cell types in the tumor, thereby causing relapse of the disease. Thus,
      drugs that selectively target cancer stem cells offer great promise for cancer
      treatment, particularly in combination with chemotherapy. Here, we show that low
      doses of metformin, a standard drug for diabetes, inhibits cellular
      transformation and selectively kills cancer stem cells in four genetically
      different types of breast cancer. The combination of metformin and a well-defined
      chemotherapeutic agent, doxorubicin, kills both cancer stem cells and non-stem
      cancer cells in culture. Furthermore, this combinatorial therapy reduces tumor
      mass and prevents relapse much more effectively than either drug alone in a
      xenograft mouse model. Mice seem to remain tumor-free for at least 2 months after
      combinatorial therapy with metformin and doxorubicin is ended. These results
      provide further evidence supporting the cancer stem cell hypothesis, and they
      provide a rationale and experimental basis for using the combination of metformin
      and chemotherapeutic drugs to improve treatment of patients with breast (and
      possibly other) cancers.

PMID- 19752086
TI  - Regulatory myeloid suppressor cells in health and disease.

PMID- 19752087
TI  - Correction of the abnormal trafficking of primary myelofibrosis CD34+ cells by
      treatment with chromatin-modifying agents.
AB  - The abnormal trafficking of CD34+ cells is a unique characteristic of primary
      myelofibrosis (PMF). We have further studied the behavior of PMF CD34+ cells by
      examining their homing to the marrow and the spleens of nonobese diabetic/severe
      combined immunodeficient (NOD/SCID) mice. Following the infusion of PMF and
      normal granulocyte colony-stimulating factor-mobilized peripheral blood (mPB)
      CD34+ cells into NOD/SCID mice, reduced numbers of PMF CD34+ cells and
      granulocyte-macrophage colony-forming unit (CFU-GM) compared with mPB were
      detected in the marrow of these mice, whereas similar numbers of PMF and mPB
      CD34+ cells and CFU-GM homed to their spleens. The abnormal homing of PMF CD34+
      cells was associated with reduced expression of CXCR4, but was not related to the
      presence of JAK2V617F. The sequential treatment of PMF CD34+ cells with the
      chromatin-modifying agents 5-aza-2'-deoxycytidine (5azaD) and trichostatin A
      (TSA), but not treatment with small molecule inhibitors of JAK2, resulted in the
      generation of increased numbers of CD34+CXCR4+ cells, which was accompanied by
      enhanced homing of PMF CD34+ cells to the marrow but not the spleens of NOD/SCID
      mice. Following 5azaD/TSA treatment, JAK2V617F-negative PMF hematopoietic
      progenitor cells preferentially homed to the marrow but not the spleens of
      recipient mice. Our data suggest that PMF CD34+ cells are characterized by a
      reduced ability to home to the marrow but not the spleens of NOD/SCID mice and
      that this homing defect can be corrected by sequential treatment with chromatin
      modifying agents.

PMID- 19752088
TI  - Lessons from applied ecology: cancer control using an evolutionary double bind.
AB  - Because the metastatic cascade is largely governed by the ability of malignant
      cells to adapt and proliferate at the distant tissue site, we propose that
      disseminated cancers are analogous in many important ways to the evolutionary and
      ecological dynamics of exotic species. Although pests can be decimated through
      the application of chemical toxins, this strategy virtually never achieves robust
      control as evolution of resistant phenotypes typically permits population
      recovery to pretreatment levels. In general, biological strategies that introduce
      predators, parasitoids, or pathogens have achieved more durable control of pest
      populations even after emergence of resistant phenotypes. From this we propose
      that long term outcome from any treatment strategy for invasive pests, including
      cancer, is not limited by evolution of resistance, but rather by the phenotypic
      cost of that resistance. If a cancerous cell's adaptation to therapy is achieved
      by upregulating xenobiotic metabolism or a redundant signaling pathway, the
      required investment in resources is small, and the original malignant phenotype
      remains essentially intact. As a result, the cancer cells' initial high level of
      fitness is little changed and unconstrained proliferation will resume once
      resistance evolves. Robust population control is possible if resistance to
      therapy requires a substantial and costly phenotypic adaptation that also
      significantly reduces the organism's fitness in its original niche: an
      evolutionary double bind.

PMID- 19752089
TI  - A role for the clock gene per1 in prostate cancer.
AB  - Circadian rhythms regulate diverse physiologic processes, including homeostatic
      functions of steroid hormones and their receptors. Perturbations of these rhythms
      are associated with pathogenic conditions, such as depression, diabetes, and
      cancer. Androgens play an important role in both normal development and
      carcinogenesis of the prostate. In the present study, we investigated a potential
      role for the core clock factor Per1 in the pathogenesis of prostate cancer. Serum
      shocked synchronized prostate cancer cells displayed disrupted circadian rhythms
      compared with the normal prostate tissue. Using Oncomine to perform a meta
      analysis of microarray expression studies, we found that Per1 is down-regulated
      in human prostate cancer samples compared with normal prostates. Reporter assays
      showed that Per1 inhibited transactivation of the androgen receptor (AR) both in
      293T cells overexpressing the AR and in the prostate cancer cell line LNCaP.
      Forced expression of Per1 in LNCaP cells diminished the expression of known
      androgen-sensitive genes following stimulation with dihydrotestosterone. We
      showed that Per1 physically interacted with AR; in addition, we found that Per1
      itself is regulated by androgens in prostate cancer cells. Overexpression of Per1
      in prostate cancer cells resulted in significant growth inhibition and apoptosis.
      Our results support the emerging role of circadian genes as key players in
      malignant transformation. Further elucidating the connections between clock genes
      and the AR pathway could benefit the development of new therapeutic strategies
      for prostate cancer as well as provide insights into chronotherapy as a way to
      optimize current therapies.

PMID- 19752090
TI  - Croatian court vindicates journal editor.

PMID- 19752091
TI  - CMA president-elect focuses on patient-centred care.

PMID- 19752092
TI  - Canadian health care slurs dismissed as "rhetoric".

PMID- 19752093
TI  - Voting on a social contract.

PMID- 19752094
TI  - Full speed ahead for CMA's transformation train.

PMID- 19752095
TI  - Iodine deficiency disorders still prevalent in China.

PMID- 19752096
TI  - Socially based discrimination against clinically appropriate care.

PMID- 19752097
TI  - The H1N1 vaccine race: can we beat the pandemic?

PMID- 19752100
TI  - Urgent air-medical transport: Right patient, place and time.

PMID- 19752101
TI  - Cases: Reversible cerebellar syndrome caused by metronidazole.

PMID- 19752102
TI  - Effective population-wide public health interventions to promote sodium
      reduction.

PMID- 19752103
TI  - Spontaneous pneumomediastinum.

PMID- 19752104
TI  - Coping with the mystery of death.

PMID- 19752105
TI  - Incidence and predictors of critical events during urgent air-medical transport.
AB  - BACKGROUND: Little is known about the risks of urgent air-medical transport used
      in regionalized health care systems. We sought to determine the incidence of in
      transit critical events and identify factors associated with these events.
      METHODS: We conducted a population-based, retrospective cohort study using
      clinical and administrative data. We included all adults undergoing urgent air
      medical transport in the Canadian province of Ontario between Jan. 1, 2004, and
      May 31, 2006. The primary outcome was in-transit critical events, which we
      defined as death, major resuscitative procedure, hemodynamic deterioration, or
      inadvertent extubation or respiratory arrest. RESULTS: We identified 19 228
      patients who underwent air-medical transport during the study period. In-transit
      critical events were observed in 5.1% of all transports, for a rate of 1 event
      per 12.6 hours of transit time. Events consisted primarily of new hypotension or
      airway management procedures. Independent predictors of critical events included
      female sex (adjusted odds ratio [OR] 1.3, 95% confidence interval [CI] 1.1-1.5),
      assisted ventilation before transport (adjusted OR 3.0, 95% CI 2.3-3.7),
      hemodynamic instability before transport (adjusted OR 3.2, 95% CI 2.5-4.1),
      transport in a fixed-wing aircraft (adjusted OR 1.5, 95% CI 1.2-1.8), increased
      duration of transport (adjusted OR 1.02 per 10-minute increment, 95% CI 1.01
      1.03), on-scene calls (adjusted OR 1.7, 95% CI 1.4-2.1) and type of crew
      (adjusted OR 0.6 for advanced care paramedics v. critical care paramedics, 95% CI
      0.5-0.7). INTERPRETATION: Critical events occurred in about 1 in every 20 air
      medical transports and were associated with multiple risk factors at the patient,
      transport and system levels. These findings have implications for the refinement
      of training of paramedic transport crews and processes for triage and transport.

PMID- 19752106
TI  - Asthma: epidemiology, etiology and risk factors.

PMID- 19752108
TI  - Agonist and blocking actions of choline and tetramethylammonium on human muscle
      acetylcholine receptors.
AB  - Choline has been used widely as an agonist for the investigation of gain-of
      function mutants of the nicotinic acetylcholine receptor. It is useful because it
      behaves like a partial agonist. The efficacy of choline is difficult to measure
      because choline blocks the channel at concentrations about four times lower than
      those that activate it. We have fitted activation mechanisms to single-channel
      activity elicited from HEK-expressed human recombinant muscle nicotinic receptors
      by choline and by tetramethylammonium (TMA). Channel block by the agonist was
      incorporated into the mechanisms that were fitted, and block was found not to be
      selective for the open state. The results also suggest that channel block is very
      fast and that the channel can shut almost as fast as normal when the blocker was
      bound. Single-channel data are compatible with a mechanism in which choline is
      actually a full agonist, its maximum response being limited only by channel
      block. However, they are also compatible with a mechanism incorporating a pre
      opening conformation change ('flip') in which choline is a genuine partial
      agonist. The latter explanation is favoured by concentration jump experiments,
      and by the fact that only this mechanism fits the TMA data. We propose that
      choline, like TMA, is a partial agonist because it is very ineffective
      (approximately 600-fold less than acetylcholine) at eliciting the initial, pre
      opening conformation change. Once flipping has occurred, all agonists, even
      choline, open the channel with similar efficiency.

PMID- 19752109
TI  - GABA(A) receptors, gephyrin and homeostatic synaptic plasticity.
AB  - Homeostatic synaptic plasticity describes the changes in synapse gain and
      function that occur in response to global changes in neuronal activity to
      maintain the stability of neuronal networks. In this review, we argue that a
      coordinated regulation of excitatory and inhibitory synaptic transmission is
      essential for maintaining CNS function while allowing both global and local
      changes in synaptic strength and connectivity. Therefore, we postulate that
      homeostatic synaptic plasticity depends on signalling cascades regulating in
      parallel the efficacy of glutamatergic and GABAergic transmission. Since
      neurotransmitter receptors interact closely with scaffolding proteins in the
      postsynaptic density, this coordinated regulation of excitatory and inhibitory
      synaptic transmission probably involves posttranslational modifications of
      scaffolding proteins, which in turn modulate local synaptic function. Here we
      review the current state of knowledge on the regulation of GABA(A) receptors and
      their main scaffolding protein gephyrin by posttranslational modifications; we
      outline future lines of research that might contribute to furthering our
      understanding of the molecular mechanisms regulating GABAergic synapse function
      and homeostatic plasticity.

PMID- 19752110
TI  - Loose coupling between calcium channels and sites of exocytosis in chromaffin
      cells.
AB  - Calcium microdomains generated by tight clusters of calcium channels regulate
      fusion of small vesicles at the synaptic terminal and have also been suggested to
      trigger exocytosis of large dense-core vesicles from neuroendocrine cells. To
      test this idea, we have compared sites of exocytosis and the spatial distribution
      of calcium channels in chromaffin cells. Fusion of individual vesicles was
      visualized using interference reflection microscopy and the submembranous calcium
      signal was assessed using total internal reflection fluorescence microscopy.
      Depolarization triggered a burst of exocytosis from up to seven sites in a
      membrane area of 11 microm(2), but these sites did not colocalize with calcium
      microdomains. Instead, calcium influx occurred in large patches (averaging 34
      microm(2)) containing a mixture of P/Q- and N-type channels. About 20% of fusion
      events occurred outside calcium channel patches. Further, the delay between the
      onset of stimulation and a burst of exocytosis was prolonged for several seconds
      by increasing the concentration of the slow calcium chelator EGTA from 1.5 to 5
      mM. These results demonstrate that while calcium channels and release sites tend
      to congregate in specialized regions of the surface membrane, these have
      dimensions of several micrometres. The dominant calcium signal regulating release
      in chromaffin cells is generated by the cooperative action of many channels
      operating over distances of many micrometres rather than discrete clusters of
      calcium channels generating localized microdomains.

PMID- 19752111
TI  - Elucidation of the gating of the GIRK channel using a spectroscopic approach.
AB  - The traditional view of G protein-coupled receptor (GPCR)-mediated signalling
      puts the players in this signalling cascade, namely the GPCR, the G protein and
      its effector, as individual components in space, where the signalling specificity
      is obtained mainly by the interaction of the GPCR and the Galpha subunits of the
      G protein. A question is then raised as to how fidelity in receptor signalling is
      achieved, given that many systems use the same components of the G protein
      signalling machinery. One possible mechanism for obtaining the specific flow of
      the downstream signals, from the activated G protein to its specific effector
      target, in a timely manner, is compartmentalization, a spatial arrangement of the
      complex in a rather restricted space. Here we review our recent findings related
      to these issues, using the G protein-coupled potassium channel (GIRK) as a model
      effector and fluorescence-based approaches to reveal how the signalling complex
      is arranged and how the G protein exerts its action to activate the GIRK channel
      in intact cells.

PMID- 19752112
TI  - The diseasome of physical inactivity--and the role of myokines in muscle--fat
      cross talk.
AB  - Type 2 diabetes, cardiovascular diseases, colon cancer, breast cancer, dementia
      and depression constitute a cluster of diseases, which defines 'a diseasome of
      physical inactivity'. Both physical inactivity and abdominal adiposity,
      reflecting accumulation of visceral fat mass, are associated with the occurrence
      of the diseases within the diseasome. Physical inactivity appears to be an
      independent and strong risk factor for accumulation of visceral fat, which again
      is a source of systemic inflammation. Chronic inflammation is involved in the
      pathogenesis of insulin resistance, atherosclerosis, neurodegeneration and tumour
      growth. Evidence suggests that the protective effect of exercise may to some
      extent be ascribed to the anti-inflammatory effect of regular exercise, which can
      be mediated via a reduction in visceral fat mass and/or by induction of an anti
      inflammatory environment with each bout of exercise. The finding that muscles
      produce and release myokines provides a conceptual basis to understand the
      mechanisms whereby exercise influences metabolism and exerts anti-inflammatory
      effects. According to our theory, contracting skeletal muscles release myokines,
      which work in a hormone-like fashion, exerting specific endocrine effects on
      visceral fat. Other myokines work locally within the muscle via paracrine
      mechanisms, exerting their effects on signalling pathways involved in fat
      oxidation.

PMID- 19752113
TI  - Interactions between short-interval intracortical inhibition and short-latency
      afferent inhibition in human motor cortex.
AB  - Transcranial magnetic stimulation (TMS) allows the testing of various inhibitory
      processes in human motor cortex. Here we aimed at gaining more insight into the
      underlying physiology by studying the interactions between short-interval
      intracortical inhibition (SICI) and short-latency afferent inhibition (SAI). SICI
      and SAI were examined in a slightly contracting hand muscle of healthy subjects
      by measuring inhibition of a test motor-evoked potential conditioned by a sub
      threshold motor cortical magnetic pulse (S1) or an electrical pulse (P) applied
      to the ulnar nerve at the wrist, respectively. SICI alone and SAI alone had
      similar magnitude when S1 intensity was set to 90% active motor threshold and P
      intensity to three times the perceptual sensory threshold. SICI was reduced or
      even disinhibited when P was co-applied, and SAI was reduced or disinhibited when
      S1 was co-applied. These interactions did not depend on the exact timing of
      arrival of P and S1 in motor cortex. A control experiment with a S1 intensity
      lowered to 70% active motor threshold excluded a contribution by short-interval
      intracortical facilitation. Finally, SICI with co-applied P correlated linearly
      with SICI alone with a slope of the regression line close to 1 whereas SAI did
      not correlate with SAI when S1 was co-applied with a slope of the regression line
      close to zero. Data indicate that S1 largely eliminates the effects of P when
      applied together, suggesting dominance of S1 over P. Findings strongly support
      the idea that SICI and SAI are mediated through two distinct and reciprocally
      connected subtypes of GABAergic inhibitory interneurons with convergent
      projections onto the corticospinal neurons. Furthermore, dominance of S1 over P
      is compatible with the notion that the SICI interneurons target the corticospinal
      neurons closer to their axon initial segment than the SAI interneurons.

PMID- 19752114
TI  - Vasomotor and respiratory responses evoked from the dorsolateral periaqueductal
      grey are mediated by the dorsomedial hypothalamus.
AB  - Activation of neurons in the dorsomedial hypothalamus (DMH) evokes increases in
      mean arterial pressure (MAP), sympathetic activity, heart rate (HR) and
      respiratory activity. Results of previous studies suggest that the DMH-evoked
      increases in MAP and HR are mediated by neurons within the periaqueductal grey
      (PAG), but a recent study has proposed that the converse is also true, i.e. that
      increases in MAP and HR evoked from the PAG depend upon neuronal activity in the
      DMH. In this study in anaesthetized rats, we examined the functional relationship
      between the DMH and PAG in regulating renal sympathetic nerve activity (RSNA) and
      respiratory activity (determined by measuring phrenic nerve activity (PNA)).
      Bilateral microinjections of the neuronal inhibitor muscimol into the DMH
      virtually abolished the increases in MAP, RSNA and PNA burst rate and amplitude
      evoked from the dorsolateral (dl) PAG. In contrast, multiple bilateral injections
      of much larger (10 times) doses of muscimol or of the local anaesthetic
      lignocaine into sites in the dlPAG at three different rostrocaudal levels did not
      reduce the magnitude or duration of the sympathetic vasomotor and respiratory
      responses evoked by disinhibition of neurons in the DMH. Thus, sympathetic
      vasomotor and respiratory responses generated from the dlPAG are dependent upon
      neuronal activity in the DMH, but not the converse. The results of this study
      together with those of previous studies indicate that the PAG regulates
      cardiovascular and respiratory function via both ascending projections to the DMH
      and descending projections to the ventral medulla, that originate from different
      PAG subregions.

PMID- 19752115
TI  - Dynamic aspects of functional regulation of the ATP receptor channel P2X2.
AB  - The P2X(2) channel is a ligand-gated channel activated by ATP. Functional
      features that reflect the dynamic flexibility of the channel include time
      dependent pore dilatation following ATP application and direct inhibitory
      interaction with activated nicotinic acetylcholine receptors on the membrane. We
      have been studying the mechanisms by which P2X(2) channel functionality is
      dynamically regulated. Using a Xenopus oocyte expression system, we observed that
      the pore properties, including ion selectivity and rectification, depend on the
      open channel density on the membrane. Pore dilatation was apparent when the open
      channel density was high and inward rectification was modest. We also observed
      that P2X(2) channels show voltage dependence, despite the absence of a canonical
      voltage sensor. At a semi-steady state after ATP application, P2X(2) channels
      were activated upon membrane hyperpolarization. This voltage-dependent activation
      was also [ATP] dependent. With increases in [ATP], the speed of hyperpolarization
      induced activation was increased and the conductance-voltage relationship was
      shifted towards depolarized potentials. Based on analyses of experimental data
      and various simulations, we propose that these phenomena can be explained by
      assuming a fast ATP binding step and a rate-limiting voltage-dependent gating
      step. Complete elucidation of these regulatory mechanisms awaits dynamic imaging
      of functioning P2X(2) channels.

PMID- 19752116
TI  - Beyond epidemiology: field studies and the physiology laboratory as the whole
      world.
AB  - There is no exercise training regimen broadly available in the field to increase
      physical fitness and prevent lifestyle-related diseases in middle-aged and older
      people. We have developed interval walking training (IWT) repeating five or more
      sets of 3 min fast walking at 70% peak aerobic capacity for walking (w ) per day
      with intervening 3 min slow walking at 40% w , for 4 days week(1), for 5 months.
      Moreover, to determine w in individuals and also to measure their energy
      expenditure even while incline walking, we have developed a portable calorimeter.
      Further, to instruct subjects on IWT even if they live remotely from the
      trainers, we have developed e-Health Promotion System. This transfers individual
      energy expenditure during IWT stored on the meter to a central server through the
      internet; it sends back the achievement to individuals along with advice
      generated automatically by the sever according to a database on 4000 subjects.
      Where we found that 5 months of IWT increased physical fitness and improved the
      indices of lifestyle-related diseases by 10-20% on average. Since our system is
      run at low cost with fewer staff for more subjects, it enables us to develop
      exercise prescriptions appropriate for individuals.

PMID- 19752117
TI  - Protein and carbohydrate supplementation increases aerobic and thermoregulatory
      capacities.
AB  - The incidence of heat illness and heat stroke is greater in older than younger
      people. In this context, exercise training regimens to increase heat tolerance in
      older people may provide protection against heat illness. Acute increases in
      plasma volume (PV) improve thermoregulation during exercise in young subjects,
      but there is some evidence that changes in PV in response to acute exercise are
      blunted in older humans. We recently demonstrated that protein-carbohydrate (Pro
      CHO) supplementation immediately after a bout of exercise increased PV and plasma
      albumin content (Alb(cont)) after 23 h in both young and older subjects. We also
      examined whether Pro-CHO supplementation during aerobic training enhanced
      thermoregulation by increasing PV and Alb(cont) in older subjects. Older men aged
      68 years exercised at moderate intensity, 60 min day(1), 3 days week(1), for 8
      weeks, at 19 degrees C, and took either placebo (CNT; 0.5 kcal, 0 g protein
      kg(1)) or Pro-CHO supplement (Pro-CHO; 3.2 kcal, 0.18 g protein kg(1))
      immediately after exercise. After training, we found during exercise at 30
      degrees C that increases in oesophageal temperature (T(es)) were attenuated more
      in Pro-CHO than CNT and associated with enhanced cutaneous vasodilatation and
      sweating. We also confirmed similar results in young subjects after 5 days of
      training. These results demonstrate that post-exercise protein and CHO
      consumption enhance thermoregulatory adaptations especially in older subjects and
      provide insight into potential strategies to improve cardiovascular and
      thermoregulatory adaptations to exercise in both older and younger subjects.

PMID- 19752118
TI  - Differences in sodium voltage-gated channel properties according to myosin heavy
      chain isoform expression in single muscle fibres.
AB  - The myosin heavy chain (MHC) isoform determines the characteristics and
      shortening velocity of muscle fibres. The functional properties of the muscle
      fibre are also conditioned by its membrane excitability through the
      electrophysiological properties of sodium voltage-gated channels. Macropatch
      clamp is used to study sodium channels in fibres from peroneus longus (PL) and
      soleus (Sol) muscles (Wistar rats, n = 8). After patch-clamp recordings, single
      fibres are identified by SDS-PAGE electrophoresis according to their myosin heavy
      chain isoform (slow type I and the three fast types IIa, IIx, IIb).
      Characteristics of sodium currents are compared (Student's t test) between fibres
      exhibiting only one MHC isoform. Four MHC isoforms are identified in PL and only
      type I in Sol single fibres. In PL, maximal sodium current (I(max)), maximal
      sodium conductance (g(Na,max)) and time constants of activation and inactivation
      ((m) and (h)) increase according to the scheme I-->IIa-->IIx-->IIb (P < 0.05).
      (m) values related to sodium channel type and/or function, are similar in Sol I
      and PL IIb fibres (P = 0.97) despite different contractile properties. The
      voltage dependence of activation (V(a,1/2)) shows a shift towards positive
      potentials from Sol type I to IIa, IIx and finally IIb fibres from PL (P < 0.05).
      These data are consistent with the earlier recruitment of slow fibres in a fast
      mixed muscle like PL, while slow fibres of postural muscle such as soleus could
      be recruited in the same ways as IIb fibres in a fast muscle.

PMID- 19752119
TI  - Activation of the retrotrapezoid nucleus by posterior hypothalamic stimulation.
AB  - The retrotrapezoid nucleus (RTN) contains chemically defined neurons (ccRTN
      neurons) that provide a pH-regulated excitatory drive to the central respiratory
      pattern generator. Here we test whether ccRTN neurons respond to stimulation of
      the perifornical hypothalamus (PeF), a region that regulates breathing during
      sleep, stress and exercise. PeF stimulation with gabazine increased blood
      pressure, phrenic nerve discharge (PND) and the firing rate of ccRTN neurons in
      isoflurane-anaesthetized rats. Gabazine produced an approximately parallel upward
      shift of the steady-state relationship between ccRTN neuron firing rate and end
      tidal CO(2), and a similar shift of the relationship between PND and end-tidal
      CO(2). The central respiratory modulation of ccRTN neurons persisted after
      gabazine without a change in pattern. Morphine administration typically abolished
      PND and reduced the discharge rate of most ccRTN neurons (by 25% on average).
      After morphine administration, PeF stimulation activated the ccRTN neurons
      normally but PND activation and the central respiratory modulation of the ccRTN
      neurons were severely attenuated. In the same rat preparation, most (58%) ccRTN
      neurons expressed c-Fos after exposure to hypercapnic hyperoxia (6-7% end-tidal
      CO(2); 3.5 h; no hypothalamic stimulation) and 62% expressed c-Fos under
      hypocapnia (approximately 3% end-tidal CO(2)) after PeF stimulation. Under
      baseline conditions (approximately 3% end-tidal CO(2), hyperoxia, no PeF
      stimulation) few (11%) ccRTN neurons expressed c-Fos. In summary, most ccRTN
      neurons are excited by posterior hypothalamic stimulation while retaining their
      normal response to CNS acidification. ccRTN neurons probably contribute both to
      the chemical drive of breathing and to the feed-forward control of breathing
      associated with emotions and or locomotion.

PMID- 19752120
TI  - Activation of M2 muscarinic receptors leads to sustained suppression of
      hippocampal transmission in the medial prefrontal cortex.
AB  - Cholinergic innervation of the prefrontal cortex is critically involved in
      arousal, learning and memory. Dysfunction of muscarinic acetylcholine receptors
      and their downstream signalling pathways has been identified in mental
      retardation. To assess the role played by the muscarinic receptors at the
      hippocampal-frontal cortex synapses, an important relay in information storage,
      we used a newly developed frontal slice preparation in which hippocampal afferent
      fibres are preserved. Transient activation of muscarinic receptors by carbachol
      results in a long-lasting depression of synaptic efficacy at the hippocampal but
      not cortical pathways or local circuitry. On the basis of a combination of
      electrophysiological, pharmacological and anatomical results, this input-specific
      muscarinic modulation can be partially attributed to the M2 subtype of muscarinic
      receptors, possibly through a combination of pre- and postsynaptic mechanisms.

PMID- 19752121
TI  - Flexible spike timing of layer 5 neurons during dynamic beta oscillation shifts
      in rat prefrontal cortex.
AB  - Human brain oscillations occur in different frequency bands that have been linked
      to different behaviours and cognitive processes. Even within specific frequency
      bands such as the beta- (14-30 Hz) or gamma-band (30-100 Hz), oscillations
      fluctuate in frequency and amplitude. Such frequency fluctuations most probably
      reflect changing states of neuronal network activity, as brain oscillations arise
      from the correlated synchronized activity of large numbers of neurons. However,
      the neuronal mechanisms governing the dynamic nature of amplitude and frequency
      fluctuations within frequency bands remain elusive. Here we show that in acute
      slices of rat prefrontal cortex (PFC), carbachol-induced oscillations in the beta
      band show frequency and amplitude fluctuations. Fast and slow non-harmonic
      frequencies are distributed differentially over superficial and deep cortical
      layers, with fast frequencies being present in layer 3, while layer 6 only showed
      slow oscillation frequencies. Layer 5 pyramidal cells and interneurons experience
      both fast and slow frequencies and they time their spiking with respect to the
      dominant frequency. Frequency and phase information is encoded and relayed in the
      layer 5 network through timed excitatory and inhibitory synaptic transmission.
      Our data indicate that frequency fluctuations in the beta-band reflect
      synchronized activity in different cortical subnetworks, that both influence
      spike timing of output layer 5 neurons. Thus, amplitude and frequency
      fluctuations within frequency bands may reflect activity in distinct cortical
      neuronal subnetworks that may process information in a parallel fashion.

PMID- 19752122
TI  - Reduction of low grade inflammation restores blunting of postprandial muscle
      anabolism and limits sarcopenia in old rats.
AB  - Ageing is characterized by a decline in muscle mass that could be explained by a
      defect in the regulation of postprandial muscle protein metabolism. Indeed, the
      stimulatory effect of food intake on protein synthesis and its inhibitory effect
      on proteolysis is blunted in old muscles from both animals and humans. Recently,
      low grade inflammation has been suspected to be one of the factors responsible
      for the decreased sensitivity of muscle protein metabolism to food intake. This
      study was undertaken to examine the effect of long-term prevention of low grade
      inflammation on muscle protein metabolism during ageing. Old rats (20 months of
      age) were separated into two groups: a control group and a group (IBU) in which
      low grade inflammation had been reduced with a non-steroidal anti inflammatory
      drug (ibuprofen). After 5 months of treatment, inflammatory markers and cytokine
      levels were significantly improved in treated old rats when compared with the
      controls: -22.3% fibrinogen, -54.2% alpha2-macroglobulin, +12.6% albumin, -59.6%
      IL(6) and -45.9% IL(1beta) levels. As expected, food intake had no effect on
      muscle protein synthesis or muscle proteolysis in controls whereas it
      significantly increased muscle protein synthesis by 24.8% and significantly
      decreased proteolysis in IBU rats. The restoration of muscle protein anabolism at
      the postprandial state by controlling the development of low grade inflammation
      in old rats significantly decreased muscle mass loss between 20 and 25 months of
      age. In conclusion, the observations made in this study have identified low grade
      inflammation as an important target for pharmacological, nutritional and
      lifestyle interventions that aim to limit sarcopenia and muscle weakness in the
      rapidly growing elderly population in Europe and North America.

PMID- 19752123
TI  - Vesicular release mode shapes the postsynaptic response at hippocampal synapses.
AB  - Release of neurotransmitters from synaptic vesicles is a central event in
      synaptic transmission. Recent evidence suggests that synaptic vesicles fuse with
      the plasma membrane by multiple routes during exocytosis, but the regulation and
      physiological implications of this choice are unclear. At hippocampal synapses,
      two modes of synaptic vesicle exocytosis can be distinguished by virtue of the
      rate and extent of loss of a fluorescent lipid marker (FM1-43). Here these two
      modes of exocytosis were investigated with a combination of electrophysiological
      recording and fluorescence imaging. It is shown that these exocytic modes result
      in distinct postsynaptic consequences, such that so-called 'kiss-and-run'
      exocytosis results in negligible activation of AMPA receptors, compared to the
      robust postsynaptic responses elicited by apparent full fusion. In contrast NMDA
      receptors are robustly activated by this form of glutamate delivery. Addition of
      cyclothiazide, which blocks AMPA receptor desensitization, reveals that the
      relatively slow rate of release of glutamate during kiss-and-run exocytosis
      shifts the population of AMPA receptors into a desensitized state, rather than
      simply being insufficient for receptor activation. These findings provide further
      support for the existence of a fusion pore mediated mode of exocytosis, and
      demonstrate that these two exocytic modes directly affect the throughput of
      synaptic transmission.

PMID- 19752125
TI  - Preparing for pandemic (H1N1) 2009.

PMID- 19752128
TI  - Physicians, CIHR call for more H1N1 research funds.

PMID- 19752129
TI  - Physician seeks inquiry into ordeal.

PMID- 19752130
TI  - Safer toys coming, but not with Santa Claus.

PMID- 19752133
TI  - Saving my heart.

PMID- 19752134
TI  - Doctors without borders in British Columbia.

PMID- 19752135
TI  - New CMA president urges catalytic action.

PMID- 19752136
TI  - Feds may provide isotope funding.

PMID- 19752137
TI  - Enzyme therapy for Fabry patients in jeopardy.

PMID- 19752139
TI  - Controlling the complications of diabetes: it's about the sugar.

PMID- 19752140
TI  - Fabry trial set to answer "political problem".

PMID- 19752141
TI  - Invisible wounds from the Congo war.

PMID- 19752142
TI  - Climate change.

PMID- 19752143
TI  - Is the tail wagging the dog?

PMID- 19752144
TI  - Fear of statins?

PMID- 19752145
TI  - Dying for knowledge.

PMID- 19752146
TI  - The inverse groups?

PMID- 19752149
TI  - In vivo activation of gene transcription via oestrogen response elements by a
      raloxifene analogue.
AB  - Raloxifene is a selective oestrogen receptor modulator with tissue-specific
      effects. The mechanisms behind the effects of raloxifene are partly unclear, and
      the aim of the present study was to investigate whether raloxifene can activate
      the classical oestrogen-signalling pathway in vivo in three known oestrogen
      responsive organs, uterus (reproductive organ), bone (non-reproductive organ) and
      thymus (immune organ). For this purpose, we have used reporter mice with a
      luciferase gene under control of oestrogen-responsive elements (EREs), enabling
      detection of in vivo activation of gene transcription via the classical oestrogen
      pathway. Three-month-old ovariectomized ERE-luciferase mice were treated with the
      raloxifene analogue (LY117018), oestradiol (OE(2)) or vehicle for 3 weeks.
      Luciferase activation was measured in bone, uterus and thymus, and compared to
      bone parameters, and uterus and thymus weights. The raloxifene analogue affected
      bone mineral density (BMD) to the same extent as OE(2), and both treatments
      resulted in increased luciferase activity in bone. As expected, OE(2) treatment
      resulted in increased uterus weight and increased uterine luciferase activity,
      while the effect of LY117018 on uterus weight and luciferase activity was modest
      and significantly lower than the effect of OE(2). LY117018 and OE(2) treatment
      resulted in similar luciferase activation in thymus. However, only OE(2)
      treatment resulted in thymic atrophy, while no effect on thymus weight was seen
      after LY117018 treatment. In summary, the raloxifene analogue LY117018 can
      activate the classical oestrogen pathway in bone, uterus and thymus in vivo, and
      this activation is associated with BMD and uterus weight, but not thymus weight.

PMID- 19752148
TI  - Age and tissue specific differences in the development of acute insulin
      resistance following injury.
AB  - Injuries, hemorrhage, sepsis, burn, and critical illnesses all induce insulin
      resistance, and insulin resistance is strongly associated with advancing age.
      However, the effect of age on injury induced insulin resistance is not well
      studied. We performed surgical trauma in male rats of three different ages (3-, 6
      , and 10-weeks old). Rats were either hemorrhaged to a mean arterial pressure of
      35-40 mmHg and subsequently maintained at that pressure for up to 90 min, or
      maintained without hemorrhage as controls. Results indicate that insulin-induced
      intracellular signaling was diminished in liver and skeletal muscle of 6- and 10
      week old rats following trauma and hemorrhage. In even younger rats, immediately
      post-weaning ( approximately 3 weeks of age), insulin signaling was lost in
      liver, but not in skeletal muscle. Glucocorticoids can play a role in the chronic
      development of insulin resistance. Our results demonstrate that corticosterone
      levels were increased in 6- and 10-week old animals following hemorrhage, but
      little change was measured in 3-week old animals. Blockade of glucocorticoid
      synthesis prevented the development of insulin resistance in skeletal muscle, but
      not in liver of 6- and 10-week old rats. Moreover, skeletal muscle glucocorticoid
      receptor levels increased dramatically between 3 and 6 weeks of age. These
      results indicate that trauma and hemorrhage-induced hepatic insulin resistance
      occurs at all ages tested. However, there is no development of insulin resistance
      following trauma and hemorrhage in skeletal muscle of post-weaning rats. In
      skeletal muscle of 6- and 10-week old rats, inhibition of glucocorticoid levels
      prevents the development of insulin resistance.

PMID- 19752150
TI  - Melanin-concentrating hormone reduces somatolactin release from cultured goldfish
      pituitary cells.
AB  - Melanin-concentrating hormone (MCH)-containing neurons directly innervate the
      adenohypophysis in the teleost pituitary. We examined immunohistochemically the
      relationship between MCH-containing nerve fibres or endings and somatolactin (SL)
      producing cells in the goldfish pituitary. Nerve fibres or endings with MCH-like
      immunoreactivity were identified in the neurohypophysis in close proximity to the
      adenohypophysial cells showing SL-like immunoreactivity. We also examined the
      effect of MCH on SL release from cultured goldfish pituitary cells and SL
      synthesis using a cell immunoblot and a real-time PCR method. Treatment of
      individually dispersed pituitary cells with MCH 10(-7) M for 3 h decreased the
      area of SL-like immunoreactivity on immunoblots, and MCH-induced reductions in SL
      release were blocked by treatment with the mammalian MCH receptor (MCHR)
      antagonist, compound-30, at a concentration of 10(-5) M. Treatment with 10(-7) M
      MCH for 3 h did not affect sl-alpha and -beta (smtla and -b as given in the Zfin
      Database) mRNA expression levels. These led us to explore the signal transduction
      mechanism leading to the inhibition of SL release, for which we examined whether
      MCH-induced reductions in SL release are mediated by the G(i) or G(q) protein
      coupled signalling pathway. The MCH-induced reductions in SL release were
      abolished by treatment with the G(i/o) protein inhibitors, NF023 (10(-5) M) or
      pertussis toxin (260 ng/ml), but not by the phospholipase C inhibitor, U-73122
      (3x10(-6) M). These results indicate that MCH can potentially function as a
      hypothalamic factor suppressing SL release via the MCHR, and subsequently through
      the G(i) protein to inhibit the adenylate cyclase/cAMP/protein kinase A
      signalling pathway in goldfish pituitary cells.

PMID- 19752151
TI  - Spontaneous circumferential esophageal dissection in a young man with
      eosinophilic esophagitis.
AB  - Spontaneous esophageal dissection is a rare condition that may happen in patients
      with eosinophilic esophagitis. Conservative management is an important
      therapeutic option to be considered. We describe an unusual case of a young man
      with eosinophilic esophagitis who presented complaining of acute retrosternal
      pain, fever and vomiting. After a thorough evaluation including CT-scan and
      esophagogram, circumferential esophageal dissection and mediastinal abscess
      without visible perforation was observed. Abscess resolution and oral nutrition
      reintroduction was achieved with non-surgical management. Corticoid therapy was
      initiated for esophagitis treatment.

PMID- 19752152
TI  - Lung function evaluation before surgery in lung cancer patients: how are recent
      advances put into practice? A survey among members of the European Society of
      Thoracic Surgeons (ESTS) and of the Thoracic Oncology Section of the European
      Respiratory Society (ERS).

PMID- 19752153
TI  - Electromyographic analysis of knee push up plus variations: what is the influence
      of the kinetic chain on scapular muscle activity?
AB  - OBJECTIVE: First, to look for appropriate closed kinetic chain exercises to
      restore intramuscular imbalance between upper trapezius (UT) and serratus
      anterior (SA) in overhead athletes. Second, to determine the influence of using
      diagonal pattern muscle recruitment during knee push up plus (KPP) exercises on
      scapular electromyographic activity. DESIGN: Single group repeated-measures
      design. SETTING: Controlled laboratory study. PARTICIPANTS: Thirty-two physically
      active individuals in good general health who did not have a history of neck
      and/or shoulder injury or surgery nor participated in high-level overhead sports
      or performed upper limb strength training for more than 5 h/week. Interventions
      Subjects performed the standard KPP and six variations. MAIN OUTCOME
      MEASUREMENTS: Electromyographic activity of the three trapezius parts and the SA.
      RESULTS: Four exercises with a low UT/SA can be selected for rehabilitation of
      intramuscular balance: standard KPP, KPP with homolateral leg extension, KPP with
      a wobble board and homolateral leg extension and one-handed KPP. The use of a
      wobble board during KPP exercises and performance on one hand has no influence on
      SA electromyographic activity. Heterolateral leg extension during KPP stimulates
      lower trapezius activity, whereas homolateral leg extension stimulates SA
      activity. CONCLUSIONS: In case of intramuscular scapular imbalance, some
      exercises are preferable over others because of their low UT/SA ratio. The use of
      a kinetic chain approach during KPP exercises influences scapular muscle
      activity.

PMID- 19752154
TI  - Does exercise training during pregnancy influence fetal cardiovascular responses
      to an exercise stimulus? Insights from a randomised, controlled trial.
AB  - In this study, the effects of maternal physical activity level on several fetal
      haemodynamic parameters such as pulsatility index of the fetal middle cerebral
      and umbilical arteries and cerebral-to-fetal ratio, as well as on fetal heart
      rate responses to one bout of moderate exercise (20 min cycle-ergometry at
      approximately 60% of age-predicted maximum heart rate) during the third pregnancy
      trimester were assessed. 26 Sedentary and 26 physically active gravidae aged 29
      (3) and 30 (2) years, respectively, were studied. Maternal exercise did not have
      a deleterious effect on fetal haemodynamics (particularly, cerebral-to-fetal
      ratio remained within normal limits with exercise). Overall, maternal training
      status did not influence the fetal cardiovascular variables studied.

PMID- 19752155
TI  - Translation of the FMR1 mRNA is not influenced by AGG interruptions.
AB  - The fragile X mental retardation 1 (FMR1) gene contains a CGG-repeat element
      within its 5' untranslated region (5'UTR) which, for alleles with more than
      approximately 40 repeats, increasingly affects both transcription (up-regulation)
      and translation (inhibition) of the repeat-containing RNA with increasing CGG
      repeat length. Translational inhibition is thought to be due to impaired
      ribosomal scanning through the CGG-repeat region, which is postulated to form
      highly stable secondary/tertiary structure. One striking difference between
      alleles in the premutation range (55-200 CGG repeats) and those in the normal
      range (< approximately 40 repeats) is the reduced number/absence of 'expansion
      stabilizing' AGG interruptions in the larger alleles. Such interruptions, which
      generally occur every 9-11 repeats in normal alleles, are thought to disrupt the
      extended CGG-repeat hairpin structure, thus facilitating translational
      initiation. To test this hypothesis, we have measured the translational
      efficiency of CGG-repeat mRNAs with 0-2 AGG interruptions, both in vitro (rabbit
      reticulocyte lysates) and in cell culture (HEK-293 cells). We demonstrate that
      the AGG interruptions have no detectable influence on translational efficiency in
      either a cell-free system or cell culture, indicating that any AGG-repeat-induced
      alterations in secondary/tertiary structure, if present, do not involve the rate
      limiting step(s) in translational initiation.

PMID- 19752156
TI  - Small-molecule signal-transduction inhibitors: targeted therapeutic agents for
      single-gene disorders.
AB  - Mutations affecting over 2000 of the 20 000 or so genes in the human genome have
      been linked so far to specific inherited diseases, most of which are rare and
      have been poorly understood. Many of the genes involved encode components of
      intracellular signalling pathways that regulate processes such as the growth,
      proliferation, differentiation and survival or programmed death of cells during
      development and the maintenance of tissues and organs. Mutations that change the
      function of genes encoding signalling proteins thereby cause disorders ranging
      from birth defects to cancer. For Mendelian disorders, the essentially causal
      relationship between mutation and disease may present direct opportunities to
      therapeutically manipulate intracellular signalling. Here, we review recent
      examples of the use of small-molecule drugs to target components of signalling
      networks in single-gene disorders. We also consider the limitations of these
      "molecularly targeted" approaches and the difficulties in their clinical
      development as therapies for rare genetic diseases.

PMID- 19752157
TI  - Submicroscopic genomic alterations in Silver-Russell syndrome and Silver-Russell
      like patients.
AB  - BACKGROUND: Silver-Russell syndrome (SRS, OMIM 180860) features fetal and
      postnatal growth restriction and variable dysmorphisms. Genetic and epigenetic
      aberrations on chromosomes 7 and 11 are commonly found in SRS. However, a large
      fraction of SRS cases remain with unknown genetic aetiology. METHODS: 22 patients
      with a diagnosis of SRS (10 with H19 hypomethylation and 12 of unknown molecular
      aetiology) and their parents were studied with the Affymetrix 250K Sty
      microarray. Several analytical approaches were used to identify genomic
      aberrations such as copy number changes (CNCs), loss of heterozygosity (LOH) and
      uniparental disomy (UPD). Selected CNCs were verified with quantitative real-time
      PCR. RESULTS: The largest unambiguous CNCs were found in patients with previously
      molecularly unexplained SRS with relatively mild phenotypes: a heterozygous
      deletion of chromosome 15q26.3 including the IGF1R gene (2.6 Mb), an atypical
      distal 22q11.2 deletion (1.1 Mb), and a pseudoautosomal region duplication (2.7
      Mb) in a male patient. LOH regions of potential relevance to the SRS phenotype
      were also identified. Importantly, no duplications or UPD of chromosomes 7 or 11
      were identified. CONCLUSION: Unexpected submicroscopic genomic events with
      pathogenic potential were found in three patients with molecularly unexplained
      SRS that was mild. The findings emphasise that SRS is heterogeneous in genetic
      aetiology beyond the major groups of H19 hypomethylation and maternal UPD7 and
      that unbiased genome-scale screens may reveal novel genotype-phenotype
      correlations.

PMID- 19752158
TI  - A triplication of the Williams-Beuren syndrome region in a patient with mental
      retardation, a severe expressive language delay, behavioural problems and
      dysmorphisms.
AB  - BACKGROUND: Intrachromosomal triplications are rare chromosomal rearrangements.
      In most triplication cases the phenotype is similar to, but more severe than
      observed in patients with a duplication of the same region. The Williams-Beuren
      syndrome (WBS) region on 7q11.23, is prone to chromosomal rearrangements. A
      common deletion causes the well-characterised Williams-Beuren syndrome. The
      reciprocal duplication has been described in 27 families only, and is associated
      with a variable phenotype, including speech delay with (mild) mental retardation,
      autism and mild dysmorphic features. As the duplication of the WBS region is
      sometimes found inunaffected parents, initially some doubts have been raised
      about the pathogenicity of the duplication. RESULTS AND METHODS: We here describe
      the first triplication of a large part of the WBS region, detected with array CGH
      and confirmed by MLPA and FISH. The phenotypic features include mental
      retardation, a severe expressive language delay, behavioural problems and
      dysmorphisms. CONCLUSION: These features are remarkably similar, but seem more
      severe, compared to features seen in duplication patients. Therefore, our
      findings support the idea that an amplification of the WBS region is a disease
      causing event, although the penetrance might be incomplete.

PMID- 19752159
TI  - Epilepsy and mental retardation limited to females with PCDH19 mutations can
      present de novo or in single generation families.
AB  - BACKGROUND: Epilepsy and mental retardation limited to females (EFMR) is an
      intriguing X-linked disorder affecting heterozygous females and sparing
      hemizygous males. Mutations in the protocadherin 19 (PCDH19) gene have been
      identified in seven unrelated families with EFMR. METHODS AND RESULTS: Here, we
      assessed the frequency of PCDH19 mutations in individuals with clinical features
      which overlap those of EFMR. We analysed 185 females from three cohorts: 42 with
      Rett syndrome who were negative for MECP2 and CDKL5 mutations, 57 with autism
      spectrum disorders, and 86 with epilepsy with or without intellectual disability.
      No mutations were identified in the Rett syndrome and autism spectrum disorders
      cohorts suggesting that despite sharing similar clinical characteristics with
      EFMR, PCDH19 mutations are not generally associated with these disorders. Among
      the 86 females with epilepsy (of whom 51 had seizure onset before 3 years), with
      or without intellectual disability, we identified two (2.3%) missense changes.
      One (c.1671C-->G, p.N557K), reported previously without clinical data, was found
      in two affected sisters, the first EFMR family without a multigenerational family
      history of affected females. The second, reported here, is a novel de novo
      missense change identified in a sporadic female. The change, p.S276P, is
      predicted to result in functional disturbance of PCDH19 as it affects a highly
      conserved residue adjacent to the adhesion interface of EC3 of PCDH19.
      CONCLUSIONS: This de novo PCDH19 mutation in a sporadic female highlights that
      mutational analysis should be considered in isolated instances of girls with
      infantile onset seizures and developmental delay, in addition to those with the
      characteristic family history of EFMR.

PMID- 19752160
TI  - Array comparative genomic hybridisation of 52 subjects with a Smith-Magenis-like
      phenotype: identification of dosage sensitive loci also associated with
      schizophrenia, autism, and developmental delay.
AB  - BACKGROUND: Smith-Magenis syndrome (SMS) is caused by del(17)(p11.2), including
      the retinoic acid induced 1 gene (RAI1), or mutation of RAI1. Haploinsufficiency
      of RAI1 results in developmental delay, mental retardation, sleep disturbance,
      self-abusive behaviors, and most features commonly seen in SMS. In this study, 52
      subjects were referred for molecular analysis of RAI1 due to the presence of an
      SMS-like phenotype in each case. For this cohort, deletion and mutation analyses
      of RAI1 were negative; thus, the clinical diagnosis of SMS could not be confirmed
      and suggested that at least one other locus was responsible for the phenotype(s)
      observed. METHODS: Here, we present whole-genome array comparative genomic
      hybridization and detailed phenotypic data of these 52 subjects. RESULTS: This
      SMS-like cohort exhibited developmental delays, sleep disturbance, self-abusive
      behaviors, motor dysfunction, and hyperactivity of the same type and prevalence
      as that of SMS. In this analysis, we identified at least 5 new loci that likely
      contribute to the SMS-like phenotype, including CNVs that were found in more than
      one subject. Genes in these regions function in development, neurological
      integrity, and morphology, all of which are affected in SMS. CONCLUSIONS: Given
      the phenotypic overlap between SMS and the SMS-like cases, these data may provide
      some insight into the function of RAI1, including the pathways in which it may be
      involved and the genes it may regulate. These data will improve diagnosis,
      understanding, and potentially treatment of these complex behavior and mental
      retardation syndromes.

PMID- 19752161
TI  - A cohort study of recurrence patterns among more than 54,000 relatives of oral
      cleft cases in Denmark: support for the multifactorial threshold model of
      inheritance.
AB  - OBJECTIVES: To determine if the anatomical severity of oral clefting affects
      familial recurrence in a large population based sample. To provide reliable
      recurrence risk estimates for oral cleft for first, second, and third degree
      relatives. DESIGN: Population based cohort study. SETTING: Denmark. PARTICIPANTS:
      6776 individuals affected with an oral cleft born from 1952 to 2005 and 54 229
      relatives. MAIN OUTCOME MEASURES: Recurrence risk estimates for oral cleft for
      first, second, and third degree relatives and stratification by severity,
      specificity, parent of origin effect, and family size for first degree relatives.
      RESULTS: For cleft lip and palate probands we observed recurrence risks for
      first, second, and third degree relatives of respectively 3.5% (95% CI 3.1% to
      4.0%), 0.8% (95% CI 0.6% to 1.0%), and 0.6% (95% CI 0.4% to 0.8%). Individuals
      affected by the most severe oral cleft had a significantly higher recurrence risk
      among both offspring and siblings, eg, the recurrence risk for siblings of a
      proband with isolated bilateral cleft lip with cleft palate was 4.6% (95% CI 3.2
      to 6.1) versus 2.5% (95% CI 1.8 to 3.2) for a proband born with a unilateral
      defect. CONCLUSIONS: Anatomical severity does have an effect on recurrence in
      first degree relatives and the type of cleft is predictive of the recurrence
      type. Highly reliable estimates of recurrence have been provided for first
      cousins in addition to more accurate estimates for first and second degree
      relatives. These results and the majority of prior data continue to support a
      multifactorial threshold model of inheritance.

PMID- 19752162
TI  - Distinct effects of leptin and a melanocortin receptor agonist injected into
      medial hypothalamic nuclei on glucose uptake in peripheral tissues.
AB  - OBJECTIVE: The medial hypothalamus mediates leptin-induced glucose uptake in
      peripheral tissues, and brain melanocortin receptors (MCRs) mediate certain
      central effects of leptin. However, the contributions of the leptin receptor and
      MCRs in individual medial hypothalamic nuclei to regulation of peripheral glucose
      uptake have remained unclear. We examined the effects of an injection of leptin
      and the MCR agonist MT-II into medial hypothalamic nuclei on glucose uptake in
      peripheral tissues. RESEARCH DESIGN AND METHODS: Leptin or MT-II was injected
      into the ventromedial (VMH), dorsomedial (DMH), arcuate nucleus (ARC), or
      paraventricular (PVH) hypothalamus or the lateral ventricle
      (intracerebroventricularly) in freely moving mice. The MCR antagonist SHU9119 was
      injected intracerebroventricularly. Glucose uptake was measured by the 2
      [(3)H]deoxy-d-glucose method. RESULTS: Leptin injection into the VMH increased
      glucose uptake in skeletal muscle, brown adipose tissue (BAT), and heart, whereas
      that into the ARC increased glucose uptake in BAT, and that into the DMH or PVH
      had no effect. SHU9119 abolished these effects of leptin injected into the VMH.
      Injection of MT-II either into the VMH or intracerebroventricularly increased
      glucose uptake in skeletal muscle, BAT, and heart, whereas that into the PVH
      increased glucose uptake in BAT, and that into the DMH or ARC had no effect.
      CONCLUSIONS: The VMH mediates leptin- and MT-II-induced glucose uptake in
      skeletal muscle, BAT, and heart. These effects of leptin are dependent on MCR
      activation. The leptin receptor in the ARC and MCR in the PVH regulate glucose
      uptake in BAT. Medial hypothalamic nuclei thus play distinct roles in leptin- and
      MT-II-induced glucose uptake in peripheral tissues.

PMID- 19752163
TI  - Hepatic muscarinic acetylcholine receptors are not critically involved in
      maintaining glucose homeostasis in mice.
AB  - OBJECTIVE: An increase in the rate of hepatic glucose production is the major
      determinant of fasting hyperglycemia in type 2 diabetes. A better understanding
      of the signaling pathways and molecules that regulate hepatic glucose metabolism
      is therefore of great clinical importance. Recent studies suggest that an
      increase in vagal outflow to the liver leads to decreased hepatic glucose
      production and reduced blood glucose levels. Since acetylcholine (ACh) is the
      major neurotransmitter of the vagus nerve and exerts its parasympathetic actions
      via activation of muscarinic ACh receptors (mAChRs), we examined the potential
      metabolic relevance of hepatocyte mAChRs. RESEARCH DESIGN AND METHODS: We
      initially demonstrated that the M(3) mAChR is the only mAChR subtype expressed by
      mouse liver/hepatocytes. To assess the physiological role of this receptor
      subtype in regulating hepatic glucose fluxes and glucose homeostasis in vivo, we
      used gene targeting and transgenic techniques to generate mutant mice lacking or
      overexpressing M(3) receptors in hepatocytes only. RESULTS: Strikingly, detailed
      in vivo phenotyping studies failed to reveal any significant metabolic
      differences between the M(3) receptor mutant mice and their control littermates,
      independent of whether the mice were fed regular or a high-fat diet. Moreover,
      the expression levels of genes for various key transcription factors, signaling
      molecules, and enzymes regulating hepatic glucose fluxes were not significantly
      altered in the M(3) receptor mutant mice. CONCLUSIONS: This rather surprising
      finding suggests that the pronounced metabolic effects mediated by activation of
      hepatic vagal nerves are mediated by noncholinergic signaling pathways.

PMID- 19752164
TI  - 3,4-Di-O-Caffeoylquinic Acid Inhibits Angiotensin-II-Induced Vascular Smooth
      Muscle Cell Proliferation and Migration by Downregulating the JNK and PI3K/Akt
      Signaling Pathways.
AB  - We previously reported 3,4-di-O-caffeoylquinic acid (CQC) protected vascular
      endothelial cells against oxidative stress and restored impaired endothelium
      dependent vasodilatation. Here, we further investigated its anti-atherosclerotic
      effect against angiotensin II (Ang II) evoked proliferation and migration of
      cultured rat vascular smooth muscle cells (rVSMC). The results showed CQC (1-20
      MUM) clearly inhibited Ang-II-stimulated BrdU incorporation and cell migration of
      rVSMC in a concentration-dependent manner but without significant cytotoxicity.
      Western blot analysis revealed Ang II increased the phosphorylation levels of Akt
      and mitogen-activated protein kinases (MAPKs;p38, ERK1/2 and JNK) in rVSMC. In
      the presence of phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin and
      three individual MAPK inhibitors SB203580, PD98059 and SP600125, both Ang-II
      induced cell proliferation and migration were significantly attenuated, although
      to differing extents, suggesting the PI3K and MAPK signal pathways all
      participated in regulating rVSMC proliferation and migration. Also, the CQC
      pretreatment markedly suppressed Ang-II-induced phosphorylation of Akt and JNK
      rather than ERK1/2, although it failed to affect p38 phosphorylation. In
      conclusion, our data demonstrate CQC may act by down-regulating Akt, JNK and part
      of the ERK1/2 pathways to inhibit Ang-II-induced rVSMC proliferation and
      migration. The anti-atherosclerotic effect of CQC is achieved either by
      endothelial cells protection or by VSMC proliferation/migration inhibition,
      suggesting this compound may be useful in preventing vascular diseases.

PMID- 19752165
TI  - Homeopathic Doses of Gelsemium sempervirens Improve the Behavior of Mice in
      Response to Novel Environments.
AB  - Gelsemium sempervirens is used in homeopathy for treating patients with anxiety
      related symptoms, however there have been few experimental studies evaluating its
      pharmacological activity. We have investigated the effects of homeopathic doses
      of G. sempervirens on mice, using validated behavioral models. Centesimal (CH)
      dilutions/dynamizations of G. sempervirens, the reference drug diazepam (1 mg/kg
      body weight) or a placebo (solvent vehicle) were intraperitoneally delivered to
      groups of mice of CD1 strain during 8 days, then the effects were assessed by the
      Light-Dark (LD) choice test and by the Open-Field (OF) exploration test, in a
      fully blind manner. In the LD test, the mean time spent in the illuminated area
      by control and placebo-treated animals was 15.98%, for mice treated with diazepam
      it increased to 19.91% (P = .047), while with G. sempervirens 5 CH it was 18.11%
      (P = .341, non-significant). The number of transitions between the two
      compartments increased with diazepam from 6.19 to 9.64 (P < .001) but not with G.
      Sempervirens. In the OF test, G. sempervirens 5 CH significantly increased the
      time spent and the distance traveled in the central zone (P = .009 and P = .003,
      resp.), while diazepam had no effect on these OF test parameters. In a subsequent
      series of experiments, G. sempervirens 7 and 30 CH also significantly improved
      the behavioral responses of mice in the OF test (P < .01 for all tested
      variables). Neither dilutions of G. sempervirens affected the total distance
      traveled, indicating that the behavioral effect was not due to unspecific changes
      in locomotor activity. In conclusion, homeopathic doses of G. sempervirens
      influence the emotional responses of mice to novel environments, suggesting an
      improvement in exploratory behavior and a diminution of thigmotaxis or neophobia.

PMID- 19752166
TI  - Predictive analyses of biological effects of natural products: from plant
      extracts to biomolecular laboratory and computer modeling.
AB  - Year by year, the characterization of the biological activity of natural products
      is becoming more competitive and complex, with the involvement in this research
      area of experts belonging to different scientific fields, including chemistry,
      biochemistry, molecular biology, immunology and bioinformatics. These fields are
      becoming of great interest for several high-impact scientific journals, including
      eCAM. The available literature in general, and a survey of reviews and original
      articles recently published, establishes that natural products, including
      extracts from medicinal plants and essential oils, retain interesting therapeutic
      activities, including antitumor, antiviral, anti-inflammatory, pro-apoptotic and
      differentiating properties. In this commentary, we focus attention on interest in
      networks based on complementary activation and comparative evaluation of
      different experimental strategies applied to the discovery and characterization
      of bioactive natural products. A representative flow chart is shown in the paper.

PMID- 19752167
TI  - Andrographolide: a new plant-derived antineoplastic entity on horizon.
AB  - Plant-derived natural products occupy an important position in the area of cancer
      chemotherapy. Molecules such as vincristine, vinblastine, paclitaxel,
      camptothecin derivatives, epipodophyllotoxin, and so forth, are invaluable
      contributions of nature to modern medicine. However, the quest to find out novel
      therapeutic compounds for cancer treatment and management is a never-ending
      venture; and diverse plant species are persistently being studied for
      identification of prospective anticancer agents. In this regard, Andrographis
      paniculata Nees, a well-known plant of Indian and Chinese traditional system of
      medicines, has drawn attention of researchers in recent times. Andrographolide,
      the principal bioactive chemical constituent of the plant has shown credible
      anticancer potential in various investigations around the globe. In vitro studies
      demonstrate the capability of the compound of inducing cell-cycle arrest and
      apoptosis in a variety of cancer cells at different concentrations.
      Andrographolide also shows potent immunomodulatory and anti-angiogenic activities
      in tumorous tissues. Synthetic analogues of the compound have also been created
      and analyzed, which have also shown similar activities. Although it is too early
      to predict its future in cancer chemotherapy, the prologue strongly recommends
      further research on this molecule to assess its potential as a prospective
      anticancer agent.

PMID- 19752168
TI  - Irregular surface compensation for radiotherapy of the breast: correlating depth
      of the compensation surface with breast size and resultant dose distribution.
AB  - Irregular surface compensation uses dynamic multileaf collimators to modify the
      fluence to an irregular surface along the cranio-caudal axis. The depth of the
      compensation surface can be varied by specifying a user-defined parameter called
      the transmission penetration depth (TPD). In our institution, a review has been
      carried out of 60 breast patients treated using irregular surface compensation of
      the tangent fields. The effect of changes in the TPD on the dose distribution was
      investigated, and the optimum TPD was correlated with the maximum field
      separation (S(max)) along the posterior border. Reducing the TPD below 50% pushes
      the dose towards the front of the breast. This reduces hot spots at the medial
      and lateral regions next to the posterior border of the tangential fields,
      particularly for patients with large separation. In 23/60 patients, with a mean
      S(max) of 23.9 +/- 1.6 cm, a TPD between 35% and 45% was used to reduce the
      proportion of the planning target volume receiving more than 107% of the
      prescribed dose by 3.4% +/- 2.8%. Our department protocol states that, subject to
      an acceptable dose distribution, a TPD of 40% is used if S(max) is greater than
      24 cm; for smaller separations, a TPD of 50% is used.

PMID- 19752169
TI  - Characteristics of in vivo radiotherapy dosimetry.
AB  - The recent discussion and debate about the use of in vivo dosimetry as a routine
      component of the radiotherapy treatment process has not included the limitations
      introduced by the physical characteristics of the detectors. Although a robust
      calibration procedure will ensure acceptable uncertainties in the measurements of
      tumour dose, further work is required to confirm the accuracy of critical organ
      measurements with a diode or a thermoluminescent dosemeter outside the main field
      owing to limitations caused by a non-uniform X-ray energy response of the
      detector, differences between the X-ray energy spectrum inside and outside the
      main field, and contaminating electrons.

PMID- 19752170
TI  - Atypical location of germinoma in basal ganglia in adolescents: radiological
      features and treatment outcomes.
AB  - The objective of this work is to describe the imaging findings, clinical profile
      and treatment response in four Chinese adolescent patients presenting with
      ectopic germinoma arising from basal ganglia. The clinical presentation,
      treatment regimens and the imaging findings at presentation and after treatment
      were described upon retrospective review of four Chinese adolescent patients. CT
      of the brain showed mixed solid cystic mass lesions in three patients. In one
      patient, only ill-defined hyperdensity was noted in the affected basal ganglia.
      Correlative MRI brain studies showed similar findings of large solid cystic
      masses in three patients, whereas the fourth patient showed small
      hyperintensities on T2 weighted and fluid-attenuated inversion-recovery
      sequences. All lesions were confirmed to be germinomas on biopsy. Chemotherapy
      followed by radiotherapy was given to three patients. There was a dramatic
      response, with complete resolution of tumour bulk in two patients and >80%
      reduction in tumour bulk in one patient. Debulking surgery was performed in one
      subject who had received cranial radiotherapy; the last follow-up MRI showed no
      evidence of residual disease.

PMID- 19752171
TI  - Zooming method (x 2.0) of digital mammography vs digital magnification view (x
      1.8) in full-field digital mammography for the diagnosis of microcalcifications.
AB  - The purpose of this study was to determine whether the interpretation of
      microcalcifications assessed on images zoomed (x 2.0) from digital mammograms is
      at least equivalent to that from digital magnification mammography (x 1.8) with
      respect to diagnostic accuracy and image quality. Three radiologists with
      different levels of experience in mammography reviewed each full-field digital
      mammography reader set for 185 patients with pathologically proven
      microcalcification clusters, which consisted of digital magnification mammograms
      (MAGs) with a magnification factor of 1.8 and images zoomed from mammograms
      (ZOOM) with a zoom factor of 2.0. Each radiologist rated their suspicion of
      breast cancer in microcalcific lesions using a six-point scale and the image
      quality and their confidence in the decisions using a five-point scale. Results
      were analysed according to display methods using areas under the receiver
      operating characteristic curves (A(z) value) for ZOOM and MAGs to interpret
      microcalcifications, and the Wilcoxon matched pairs signed rank test for image
      quality and confidence levels. There was no statistically significant difference
      in the level of suspicion of breast cancer between the ZOOM and MAG groups (A(z)
      = 0.8680 for ZOOM; A(z) = 0.8682 for MAG; p = 0.9897). However, MAG images were
      significantly better than ZOOM images in terms of visual imaging quality (p <
      0.001), and the confidence level with MAG was better than with ZOOM (p < 0.001).
      In conclusion, the performance of radiologists in the diagnosis of
      microcalcifications using ZOOM was similar to that using MAGs, although image
      quality and confidence levels were better using MAGs.

PMID- 19752172
TI  - Genetic polymorphisms in genes encoding antioxidant enzymes are associated with
      diabetic retinopathy in type 1 diabetes.
AB  - OBJECTIVE: Oxidative stress plays an important role in the development of
      microangiopathic complications in type 1 diabetes. We investigated polymorphic
      markers in genes encoding enzymes regulating production of reactive oxygen
      species in association with diabetic retinopathy or diabetic nephropathy.
      RESEARCH DESIGN AND METHODS: A total of 124 patients with type 1 diabetes were
      investigated in this case-control study. All subjects were matched for sex, age,
      and duration of diabetes. Genotyping was conducted using real-time PCR for
      p.Val16Ala polymorphism in the MnSOD gene and c.C-262T in the promoter region of
      the CAT gene. Multiplex PCR method was used for determination of GSTM1 and GSTT1
      polymorphic deletions. Fluorescence-labeled PCR amplicons and fragment analysis
      was used for assessing the number of pentanucleotide (CCTTT)n repeats in
      inducible nitric oxide synthase. RESULTS: A positive association of MnSOD
      genotype Val/Val (odds ratio [OR] 2.49, 95% CI 1.00-6.16, P = 0.045) and GSTM1-1
      genotype (2.63, 1.07-6.47, P = 0.031) with diabetic retinopathy but not with
      diabetic nephropathy was demonstrated. Additionally, the combination of the two
      genotypes conveyed an even higher risk (4.24, 1.37-13.40, P = 0.009). No other
      investigated genetic polymorphisms were associated with either diabetic
      retinopathy or diabetic nephropathy. CONCLUSIONS: Selected polymorphisms in genes
      encoding MnSOD and GSTM1 could be added to a panel of genetic markers for
      identification of individuals with type 1 diabetes at an increased risk for
      developing diabetic retinopathy.

PMID- 19752173
TI  - From genetic risk awareness to overt type 1 diabetes: parental stress in a
      placebo-controlled prevention trial.
AB  - OBJECTIVE: To evaluate the psychological burden of parents facing increasing risk
      of type 1 diabetes in their children. RESEARCH DESIGN AND METHODS: In the
      population-based Type 1 Diabetes Prediction and Prevention (DIPP) Study, newborn
      infants with HLA-DQB1-conferred diabetes risk were enrolled in sequential
      analyses of diabetes-associated autoantibodies. Those persistently positive for
      at least two autoantibodies were recruited to a randomized double-blinded
      intervention trial. The experience of stress in parents of 664 children was
      measured using Parenting Stress Index self-report inventory. RESULTS: While
      diagnosis of diabetes increased parental stress, the appearance of autoantibodies
      or participation in the intervention trial did not. Mothers had higher stress
      levels than fathers. Single parenthood and chronically ill family members
      increased parental stress. CONCLUSIONS: Parental stress was not increased by
      notification of autoantibody positivity or by participation in an intervention
      trial. Other demanding family conditions contributed to the experience of stress.

PMID- 19752174
TI  - Low serum level of the endogenous secretory receptor for advanced glycation end
      products (esRAGE) is a risk factor for prevalent vertebral fractures independent
      of bone mineral density in patients with type 2 diabetes.
AB  - OBJECTIVE: Patients with type 2 diabetes are known to have an increased risk for
      fracture compared with non-type 2 diabetic control subjects, despite having
      higher bone mineral density (BMD). We previously showed that serum pentosidine,
      one of the advanced glycation end products (AGEs), was associated with prevalent
      vertebral fractures (VFs) in those with type 2 diabetes. The involvement of the
      endogenous secretory receptor for AGEs (esRAGE) in VFs in those with type 2
      diabetes, however, is still unknown. RESEARCH DESIGN AND METHODS: We compared
      parameters including esRAGE, pentosidine, and BMD in Japanese type 2 diabetic
      patients (137 men >50 years old and 140 postmenopausal women) with and without
      VFs. RESULTS: The esRAGE-to-pentosidine ratio in type 2 diabetic patients with
      VFs was significantly lower than in those without VFs (men: 7.1 +/- 2.8 vs. 9.4
      +/- 6.2, P = 0.013, respectively; women: 4.7 +/- 2.7 vs. 8.2 +/- 5.4, P < 0.001,
      respectively). Multivariate logistic regression analysis adjusted for age, BMI,
      A1C, serum creatinine, duration of diabetes, therapeutic agents, diabetes
      complications, osteoporotic risk factors, and lumbar BMD identified the serum
      esRAGE level and esRAGE-to-pentosidine ratio as factors associated with the
      presence of VFs, independent of BMD in men (odds ratio [OR] 0.46 [95% CI 0.25
      0.84], P = 0.012; and OR 0.34 [0.15-0.76], P = 0.009, respectively) and in women
      (OR 0.32 [0.16-0.67], P = 0.002; and OR 0.14 [0.04-0.43], P = 0.001,
      respectively). CONCLUSIONS: These results show that serum esRAGE level and esRAGE
      to-pentosidine ratio are more useful than BMD for assessing the risk of VFs in
      type 2 diabetic patients.

PMID- 19752175
TI  - Response to 'Too early to stop immigrant vaccination programmes'.

PMID- 19752177
TI  - Space-based, but not arm-based, shift in tactile processing in complex regional
      pain syndrome and its relationship to cooling of the affected limb.
AB  - Complex regional pain syndrome (CRPS) occurs after stroke, but most cases develop
      after peripheral trauma and without evidence of brain trauma. However, CRPS is
      associated with symptoms that appear similar to those observed in patients
      suffering from hemispatial neglect. Ten participants (four males) with CRPS of
      one arm performed temporal order judgements of pairs of vibrotactile stimuli, one
      delivered to each hand, at one of 10 possible stimulus onset asynchronies, under
      two conditions: arms held each side of the midline and arms crossed over the
      midline. Participants released a foot switch to indicate which hand had been
      stimulated first. The order of conditions was randomized and the foot under which
      the switch was positioned was counterbalanced. There were two blocks of 150
      trials in each condition. The stimulus onset asynchronicity at which the
      participants were equally likely to select either hand, the point of subjective
      simultaneity (PSS), was compared between conditions and between those with left
      or right-sided symptoms. When arms were not crossed, the participants prioritized
      stimuli from the unaffected limb over those from the affected limb (mean +/- SD
      PSS = 25 +/- 7.5 ms) and the magnitude of the PSS strongly related to the degree
      to which the affected hand was cooler than the unaffected hand (r = 0.942, P <
      0.001). When the arms were crossed, the effect was reversed: the participants
      prioritized stimuli from the affected limb over those from the unaffected limb
      [PSS = -18 +/- 13 ms; main effect of condition F (1, 9) = 98.6, P < 0.001]. There
      was no effect of the side of symptoms. These results show that CRPS is associated
      with a deficit in tactile processing that is defined by the space in which the
      affected limb normally resides, not by the affected limb itself, and which
      relates to the relative cooling of the affected limb. This pattern is consistent
      with data from those with hemispatial neglect after stroke and raises the
      possibility that chronic CRPS involves a type of spatial neglect.

PMID- 19752178
TI  - Comparative cost analysis of insecticide-treated net delivery strategies: sales
      supported by social marketing and free distribution through antenatal care.
AB  - Insecticide-treated nets (ITNs) are effective in substantially reducing malaria
      transmission. Still, ITN coverage in sub-Saharan Africa (SSA) remains extremely
      low. Policy makers are concerned with identifying the most suitable delivery
      mechanism to achieve rapid yet sustainable increases in ITN coverage. Little is
      known, however, on the comparative costs of alternative ITN distribution
      strategies. This paper aimed to fill this gap in knowledge by developing such a
      comparative cost analysis, looking at the cost per ITN distributed for two
      alternative interventions: subsidized sales supported by social marketing and
      free distribution to pregnant women through antenatal care (ANC). The study was
      conducted in rural Burkina Faso, where the two interventions were carried out
      alongside one another in 2006/07. Cost information was collected prospectively to
      derive both a financial analysis adopting a provider's perspective and an
      economic analysis adopting a societal perspective. The average financial cost per
      ITN distributed was US$8.08 and US$7.21 for sales supported by social marketing
      and free distribution through ANC, respectively. The average economic cost per
      ITN distributed was US$4.81 for both interventions. Contrary to common belief,
      costs did not differ substantially between the two interventions. Due to the
      district's ability to rely fully on the use of existing resources, financial
      costs associated with free ITN distribution through ANC were in fact even lower
      than those associated with the social marketing campaign. This represents an
      encouraging finding for SSA governments and points to the possibility to invest
      in programmes to favour free ITN distribution through existing health facilities.
      Given restricted budgets, however, free distribution programmes are unlikely to
      be feasible.

PMID- 19752176
TI  - Choline deficiency alters global histone methylation and epigenetic marking at
      the Re1 site of the calbindin 1 gene.
AB  - Maternal choline availability is essential for fetal neurogenesis. Choline
      deprivation (CD) causes hypomethylation of specific CpG islands in genes
      controlling cell cycling in fetal hippocampus. We now report that, in C57BL/6
      mice, CD during gestational days 12-17 also altered methylation of the histone H3
      in E17 fetal hippocampi. In the ventricular and subventricular zones, monomethyl
      lysine 9 of H3 (H3K9me1) was decreased by 25% (P<0.01), and in the pyramidal
      layer, dimethyl-lysine 9 of H3 (H3K9me2) was decreased by 37% (P<0.05). These
      changes were region specific and were not observed in whole-brain preparations.
      Also, the same effects of CD on H3 methylation were observed in E14 neural
      progenitor cells (NPCs) in culture. Changes in G9a histone methyltransferase
      might mediate altered H3K9me2,1. Gene expression of G9a was decreased by 80% in
      CD NPCs (P<0.001). In CD, H3 was hypomethylated upstream of the RE1 binding site
      in the calbindin 1 promoter, and 1 CpG site within the calbindin1 promoter was
      hypermethylated. REST binding to RE1 (recruits G9a) was decreased by 45% (P<0.01)
      in CD. These changes resulted in increased expression of calbindin 1 in CD (260%;
      P<0.05). Thus, CD modulates histone methylation in NPCs, and this could underlie
      the observed changes in neurogenesis.

PMID- 19752179
TI  - Impact of primary Sjogren's syndrome on smell and taste: effect on quality of
      life.
AB  - OBJECTIVES: To assess the prevalence of abnormal smell and taste perception in
      people with primary SS and the effect on quality of life (QoL). METHODS: Twenty
      eight participants with SS and 37 controls were enrolled in a cohort-matched,
      prospective, cross-sectional study. Smell and taste thresholds were measured
      using standardized, validated tests. QoL was assessed by the Short Form 12 (SF
      12). RESULTS: Smell threshold was reduced by 1 point (P = 0.002; 95% CI 0.35,
      1.54) and taste threshold was reduced by 3.5 points (P < 0.001; 95% CI 1.80,
      5.22) in the SS group compared with controls. The physical and mental components
      of SF-12 were reduced by 14.2 points (P < 0.001; 95% CI 9.47, 19.02) and 7.5
      points (P = 0.002; 95% CI 2.97, 12.02), respectively, in the SS group compared
      with controls. Taste threshold was significantly correlated with both the
      physical (r = 0.48; P < 0.001) and the mental (r = 0.30; P = 0.015) components of
      SF-12. Smell threshold correlated with the physical (r = 0.457; P < 0.001), but
      not the mental component (r = 0.154; P = 0.222) of SF-12. CONCLUSIONS: Clinically
      important impairment of chemosensory perception occurred in the SS group compared
      with age- and gender-matched controls. Assessment using SF-12 suggests that this
      impairment contributed to the reduced health-related QoL that characterized these
      individuals.

PMID- 19752183
TI  - XBP1 governs late events in plasma cell differentiation and is not required for
      antigen-specific memory B cell development.
AB  - The unfolded protein response (UPR) is a stress response pathway that is driven
      by the increased load of unfolded proteins in the endoplasmic reticulum of highly
      secretory cells such as plasma cells (PCs). X box binding protein 1 (XBP1) is a
      transcription factor that mediates one branch of the UPR and is crucial for the
      development of antibody-secreting PCs. PCs represent only one class of terminally
      differentiated B cells, however, and little is known about the role for XBP1 in
      the other class: memory B cells. We have developed an XBP1(fl/fl) CD19(+/cre)
      conditional knockout (XBP1(CD19)) mouse to build upon our current understanding
      of the function of XBP1 in PC differentiation as well as to explore the role of
      XBP1 in memory cell development. Using this model, we show that XBP1(CD19) mice
      are protected from disease in an autoantibody-mediated mouse lupus model. We also
      identify a novel developmental stage at which B cells express the traditional PC
      marker CD138 (syndecan-1) but have yet to undergo XBP1-dependent functional and
      morphological differentiation into antibody-secreting cells. Finally, we show
      that memory B cells develop normally in XBP1(CD19) mice, demonstrating that XBP1
      mediated functions occur independently of any memory cell lineage commitment.

PMID- 19752184
TI  - Distinct roles for E12 and E47 in B cell specification and the sequential
      rearrangement of immunoglobulin light chain loci.
AB  - The E2A gene products, E12 and E47, are critical regulators of B cell
      development. However, it remains elusive whether E12 and E47 have overlapping
      and/or distinct functions during B lymphopoiesis. We have generated mice
      deficient for either E12 or E47 and examined their roles in B cell maturation. We
      show that E47 is essential for developmental progression at the prepro-B cell
      stage, whereas E12 is dispensable for early B cell development, commitment, and
      maintenance. In contrast, both E12 and E47 play critical roles in pre-B and
      immature B cells to promote immunoglobulin lambda (Ig lambda) germline
      transcription as well as Ig lambda VJ gene rearrangement. Furthermore, we show
      that E12 as well as E47 is required to promote receptor editing upon exposure to
      self-antigen. We demonstrate that increasing levels of E12 and E47 act to induce
      Ig lambda germline transcription, promote trimethylated lysine 4 on histone 3
      (H3) as well as H3 acetylation across the J lambda region, and activate Ig lambda
      VJ gene rearrangement. We propose that in the pre-B and immature B cell
      compartments, gradients of E12 and E47 activities are established to
      mechanistically regulate the sequential rearrangement of the Ig light chain
      genes.

PMID- 19752185
TI  - GM-CSF regulates intimal cell proliferation in nascent atherosclerotic lesions.
AB  - The contribution of intimal cell proliferation to the formation of early
      atherosclerotic lesions is poorly understood. We combined 5-bromo-2'-deoxyuridine
      pulse labeling with sensitive en face immunoconfocal microscopy analysis, and
      quantified intimal cell proliferation and Ly-6C(high) monocyte recruitment in low
      density lipoprotein receptor-null mice. Cell proliferation begins in nascent
      lesions preferentially at their periphery, and proliferating cells accumulate in
      lesions over time. Although intimal cell proliferation increases in parallel to
      monocyte recruitment as lesions grow, proliferation continues when monocyte
      recruitment is inhibited. The majority of proliferating intimal cells are
      dendritic cells expressing CD11c and major histocompatibility complex class II
      and 33D1, but not CD11b. Systemic injection of granulocyte/macrophage colony
      stimulating factor (GM-CSF) markedly increased cell proliferation in early
      lesions, whereas function-blocking anti-GM-CSF antibody inhibited proliferation.
      These findings establish GM-CSF as a key regulator of intimal cell proliferation
      in lesions, and demonstrate that both proliferation and monocyte recruitment
      contribute to the inception of atherosclerosis.

PMID- 19752186
TI  - Self-class I MHC molecules support survival of naive CD8 T cells, but depress
      their functional sensitivity through regulation of CD8 expression levels.
AB  - Previous studies have suggested that naive CD8 T cells require self-peptide-major
      histocompatability complex (MHC) complexes for maintenance. However,
      interpretation of such studies is complicated because of the involvement of
      lymphopenic animals, as lymphopenia drastically alters naive T cell homeostasis
      and function. In this study, we explored naive CD8 T cell survival and function
      in nonlymphopenic conditions by using bone marrow chimeric donors and hosts in
      which class I MHC expression is absent or limited to radiosensitive versus
      radioresistant cells. We found that long-term survival of naive CD8 T cells (but
      not CD4 T cells) was impaired in the absence of class I MHC. However, distinct
      from this effect, class I MHC deprivation also enhanced naive CD8 T cell
      responsiveness to low-affinity (but not high-affinity) peptide-MHC ligands. We
      found that this improved sensitivity was a consequence of up-regulated CD8
      levels, which was mediated through a transcriptional mechanism. Hence, our data
      suggest that, in a nonlymphopenic setting, self-class I MHC molecules support CD8
      T cell survival, but that these interactions also attenuate naive T cell
      sensitivity by dynamic tuning of CD8 levels.

PMID- 19752187
TI  - On the functional use of the membrane compartmentalized pool of ATP by the Na+
      and Ca++ pumps in human red blood cell ghosts.
AB  - Previous evidence established that a sequestered form of adenosine triphosphate
      (ATP pools) resides in the membrane/cytoskeletal complex of red cell porous
      ghosts. Here, we further characterize the roles these ATP pools can perform in
      the operation of the membrane's Na(+) and Ca(2+) pumps. The formation of the
      Na(+)- and Ca(2+)-dependent phosphointermediates of both types of pumps (E(Na)-P
      and E(Ca)-P) that conventionally can be labeled with trace amounts of [gamma
      (3)P]ATP cannot occur when the pools contain unlabeled ATP, presumably because of
      dilution of the [gamma-(3)P]ATP in the pool. Running the pumps forward with
      either Na(+) or Ca(2+) removes pool ATP and allows the normal formation of
      labeled E(Na)-P or E(Ca)-P, indicating that both types of pumps can share the
      same pools of ATP. We also show that the halftime for loading the pools with bulk
      ATP is 10-15 minutes. We observed that when unlabeled "caged ATP" is entrapped in
      the membrane pools, it is inactive until nascent ATP is photoreleased, thereby
      blocking the labeled formation of E(Na)-P. We also demonstrate that ATP generated
      by the membrane-bound pyruvate kinase fills the membrane pools. Other results
      show that pool ATP alone, like bulk ATP, can promote the binding of ouabain to
      the membrane. In addition, we found that pool ATP alone functions together with
      bulk Na(+) (without Mg(2+)) to release prebound ouabain. Curiously, ouabain was
      found to block bulk ATP from entering the pools. Finally, we show, with red cell
      inside-outside vesicles, that pool ATP alone supports the uptake of (45)Ca by the
      Ca(2+) pump, analogous to the Na(+) pump uptake of (22)Na in this circumstance.
      Although the membrane locus of the ATP pools within the membrane/cytoskeletal
      complex is unknown, it appears that pool ATP functions as the proximate energy
      source for the Na(+) and Ca(2+) pumps.

PMID- 19752188
TI  - Trabeculae carneae as models of the ventricular walls: implications for the
      delivery of oxygen.
AB  - Trabeculae carneae are the smallest naturally arising collections of linearly
      arranged myocytes in the heart. They are the preparation of choice for studies of
      function of intact myocardium in vitro. In vivo, trabeculae are unique in
      receiving oxygen from two independent sources: the coronary circulation and the
      surrounding ventricular blood. Because oxygen partial pressure (PO(2)) in the
      coronary arterioles is identical in specimens from both ventricles, whereas that
      of ventricular blood is 2.5-fold higher in the left ventricle than in the right
      ventricle, trabeculae represent a "natural laboratory" in which to examine the
      influence of "extravascular" PO(2) on the extent of capillarization of myocardial
      tissue. We exploit this advantage to test four hypotheses. (1) In trabeculae from
      either ventricle, a peripheral annulus of cells is devoid of capillaries. (2)
      Hence, sufficiently small trabeculae from either ventricle are totally devoid of
      capillaries. (3) The capillary-to-myocyte ratios in specimens from either
      ventricle are identical to those of their respective walls. (4) Capillary-to
      myocyte ratios are comparable in specimens from either ventricle, reflecting
      equivalent energy demands in vivo, driven by identical contractile frequencies
      and comparable wall stresses. We applied confocal fluorescent imaging to
      trabeculae in cross section, subsequently using semi-automated segmentation
      techniques to distinguish capillaries from myocytes. We quantified the capillary
      to-myocyte ratios of trabeculae from both ventricles and compared them to those
      determined for the ventricular free walls and septum. Quantitative interpretation
      was furthered by mathematical modeling, using both the classical solution to the
      diffusion equation for elliptical cross sections, and a novel approach applicable
      to cross sections of arbitrary shape containing arbitrary disposition of
      capillaries and non-respiring collagen cords.

PMID- 19752189
TI  - EF hands at the N-lobe of calmodulin are required for both SK channel gating and
      stable SK-calmodulin interaction.
AB  - Small conductance calcium-activated potassium (SK) channels respond to
      intracellular Ca(2+) via constitutively associated calmodulin (CaM). Previous
      studies have proposed a modular design for the interaction between CaM and SK
      channels. The C-lobe and the linker of CaM are thought to regulate the
      constitutive binding, whereas the N-lobe binds Ca(2+) and gates SK channels.
      However, we found that coexpression of mutant CaM (E/Q) where the N-lobe has only
      one functional EF hand leads to rapid rundown of SK channel activity, which can
      be recovered with exogenously applied wild-type (WT), but not mutant, CaM. Our
      results suggest that the mutation at the N-lobe EF hand disrupts the stable
      interaction between CaM and SK channel subunits, such that mutant CaM dissociates
      from the channel complex when the inside of the membrane is exposed to CaM-free
      solution. The disruption of the stable interaction does not directly result from
      the loss of Ca(2+)-binding capacity because SK channels and WT CaM can stably
      interact in the absence of Ca(2+). These findings question a previous conclusion
      that CaM where the N-lobe has only one functional EF hand can stably support the
      gating of SK channels. They cannot be explained by the current model of modular
      interaction between CaM and SK channels, and they imply a role for N-lobe EF hand
      residues in binding to the channel subunits. Additionally, we found that a potent
      enhancer for SK channels, 3-oxime-6,7-dichloro-1H-indole-2,3-dione (NS309),
      enables the recovery of channel activity with CaM (E/Q), suggesting that NS309
      stabilizes the interaction between CaM and SK channels. CaM (E/Q) can regulate
      Ca(2+)-dependent gating of SK channels in the presence of NS309, but with a lower
      apparent Ca(2+) affinity than WT CaM.

PMID- 19752190
TI  - Muscle LIM protein interacts with cofilin 2 and regulates F-actin dynamics in
      cardiac and skeletal muscle.
AB  - The muscle LIM protein (MLP) and cofilin 2 (CFL2) are important regulators of
      striated myocyte function. Mutations in the corresponding genes have been
      directly associated with severe human cardiac and skeletal myopathies, and
      aberrant expression patterns have often been observed in affected muscles.
      Herein, we have investigated whether MLP and CFL2 are involved in common
      molecular mechanisms, which would promote our understanding of disease
      pathogenesis. We have shown for the first time, using a range of biochemical and
      immunohistochemical methods, that MLP binds directly to CFL2 in human cardiac and
      skeletal muscles. The interaction involves the inter-LIM domain, amino acids 94
      to 105, of MLP and the amino-terminal domain, amino acids 1 to 105, of CFL2,
      which includes part of the actin depolymerization domain. The MLP/CFL2 complex is
      stronger in moderately acidic (pH 6.8) environments and upon CFL2
      phosphorylation, while it is independent of Ca(2+) levels. This interaction has
      direct implications in actin cytoskeleton dynamics in regulating CFL2-dependent F
      actin depolymerization, with maximal depolymerization enhancement at an MLP/CFL2
      molecular ratio of 2:1. Deregulation of this interaction by intracellular pH
      variations, CFL2 phosphorylation, MLP or CFL2 gene mutations, or expression
      changes, as observed in a range of cardiac and skeletal myopathies, could impair
      F-actin depolymerization, leading to sarcomere dysfunction and disease.

PMID- 19752191
TI  - SET domains of histone methyltransferases recognize ISWI-remodeled nucleosomal
      species.
AB  - The trithorax (trxG) and Polycomb (PcG) group proteins recognize and propagate
      inheritable patterns of gene expression through a poorly understood epigenetic
      mechanism. A distinguishing feature of these proteins is the presence of a 130
      amino-acid methyltransferase domain (SET), which catalyzes the methylation of
      histones. It is still not clear how SET proteins distinguish gene expression
      states, how they are targeted, or what regulates their substrate specificity.
      Many SET domain-containing proteins show robust activity on core histones but
      relatively weak activity on intact nucleosomes, their physiological substrate.
      Here, we examined the binding of two SET domain-containing proteins, ALL1 and
      SET7, to chromatin substrates. The SET domains from these proteins bind and
      methylate intact nucleosomes poorly but can recognize disrupted nucleosomal
      structures associated with transcribed chromatin. Interestingly, the remodeling
      of dinucleosomes by the ISWI class of ATP-dependent chromatin remodeling enzymes
      stimulated the binding of SET domains to chromatin and the methylation of H3
      within the nucleosome. Unexpectedly, dinucleosomes remodeled by SWI/SNF were poor
      substrates. Thus, SET domains can distinguish nucleosomes altered by these two
      classes of remodeling enzymes. Our study reveals novel insights into the
      mechanism of how SET domains recognize different chromatin states and specify
      histone methylation at active loci.

PMID- 19752192
TI  - Nuclear factor I-C links platelet-derived growth factor and transforming growth
      factor beta1 signaling to skin wound healing progression.
AB  - Transforming growth factor beta (TGF-beta) and platelet-derived growth factor A
      (PDGFAlpha) play a central role in tissue morphogenesis and repair, but their
      interplay remain poorly understood. The nuclear factor I C (NFI-C) transcription
      factor has been implicated in TGF-beta signaling, extracellular matrix
      deposition, and skin appendage pathologies, but a potential role in skin
      morphogenesis or healing had not been assessed. To evaluate this possibility, we
      performed a global gene expression analysis in NFI-C(-/-) and wild-type embryonic
      primary murine fibroblasts. This indicated that NFI-C acts mostly to repress gene
      expression in response to TGF-beta1. Misregulated genes were prominently
      overrepresented by regulators of connective tissue inflammation and repair. In
      vivo skin healing revealed a faster inflammatory stage and wound closure in NFI
      C(-/-) mice. Expression of PDGFA and PDGF-receptor alpha were increased in wounds
      of NFI-C(-/-) mice, explaining the early recruitment of macrophages and
      fibroblasts. Differentiation of fibroblasts to contractile myofibroblasts was
      also elevated, providing a rationale for faster wound closure. Taken together
      with the role of TGF-beta in myofibroblast differentiation, our results imply a
      central role of NFI-C in the interplay of the two signaling pathways and in
      regulation of the progression of tissue regeneration.

PMID- 19752193
TI  - An innate immunity signaling process suppresses macrophage ABCA1 expression
      through IRAK-1-mediated downregulation of retinoic acid receptor alpha and
      NFATc2.
AB  - ATP-binding cassette transporter A1 (ABCA1) plays a central role in promoting
      cholesterol efflux from macrophages, thereby reducing the risk of foam cell
      formation and atherosclerosis. The expression of ABCA1 is induced by members of
      the nuclear receptor family of transcription factors, including retinoic acid
      receptors (RARs). A key innate immunity signaling kinase, IRAK-1, has been
      associated with an increased risk of atherosclerosis in humans and mice. This
      prompted us to investigate the potential connection between IRAK-1 and the
      expression of ABCA1. Here, we demonstrate that nuclear RARalpha levels are
      dramatically elevated in IRAK-1(-/-) macrophages. Correspondingly, IRAK-1(-/-)
      macrophages exhibit increased expression of ABCA1 mRNA and protein, as well as
      elevated cholesterol efflux in response to the RAR ligand ATRA. Analysis of the
      ABCA1 proximal promoter revealed binding sites for both RAR and NFAT. Chromatin
      immunoprecipitation assays demonstrated increased binding of RARalpha and NFATc2
      to the ABCA1 promoter in IRAK-1(-/-) macrophages compared to wild-type
      macrophages. Additionally, lipopolysaccharide pretreatment reduced the nuclear
      levels of RARalpha and decreased ABCA1 expression and cholesterol efflux in wild
      type but not in IRAK-1(-/-) cells. In summary, this study reveals a novel
      connection between innate immunity signaling processes and the regulation of
      ABCA1 expression in macrophages and defines a potential therapeutic target for
      treating atherosclerosis.

PMID- 19752194
TI  - A role for dynein in the inhibition of germ cell proliferative fate.
AB  - During normal development as well as in diseased states such as cancer,
      extracellular "niches" often provide cues to proximal cells and activate
      intracellular pathways. Activation of such signaling pathways in turn instructs
      cellular proliferation and differentiation. In the Caenorhabditis elegans gonad,
      GLP-1/Notch signaling instructs germ line stem cells to self-renew through
      mitotic cell division. As germ cells progressively move out of the niche, they
      differentiate by entering meiosis and eventually form gametes. In this model
      system, we uncovered an unexpected role for the dynein motor complex in promoting
      normal differentiation of proliferating germ cells. We demonstrate that dynein
      light chain 1 (DLC-1) and its partner, dynein heavy chain 1, inhibit the
      proliferative cell fate, in part through regulation of METT-10, a conserved
      putative methyltransferase. We show that DLC-1 physically interacts with METT-10
      and promotes both its overall levels and nuclear accumulation. Our results add a
      new dimension to the processes controlled by the dynein motor complex,
      demonstrating that dynein can act as an antiproliferative factor.

PMID- 19752195
TI  - Meiotic DNA double-strand break repair requires two nucleases, MRN and Ctp1, to
      produce a single size class of Rec12 (Spo11)-oligonucleotide complexes.
AB  - Programmed DNA double-strand breaks (DSBs) in meiosis are formed by Spo11 (Rec12
      in fission yeast), a topoisomerase II-like protein, which becomes covalently
      attached to DNA 5' ends. For DSB repair through homologous recombination, the
      protein must be removed from these DNA ends. We show here that Rec12 is
      endonucleolytically removed from DSB ends attached to a short oligonucleotide
      (Rec12-oligonucleotide complex), as is Spo11 in budding yeast. Fission yeast,
      however, has only one size class of Rec12-oligonucleotide complexes, whereas
      budding yeast has two size classes, suggesting different endonucleolytic
      regulatory mechanisms. Rec12-oligonucleotide generation strictly requires Ctp1
      (Sae2 nuclease homolog), the Rad32 (Mre11) nuclease domain, and Rad50 of the MRN
      complex. Surprisingly, Nbs1 is not strictly required, indicating separable roles
      for the MRN subunits. On the basis of these and other data, we propose that Rad32
      nuclease has the catalytic site for Rec12-oligonucleotide generation and is
      activated by Ctp1, which plays an additional role in meiotic recombination.

PMID- 19752197
TI  - A novel GGA-binding site is required for intracellular sorting mediated by
      stabilin-1.
AB  - Stabilin-1 is a unique scavenger receptor that combines endocytic and
      intracellular sorting functions in macrophages. Stabilin-1 mediates the
      endocytosis of acetylated low-density lipoprotein (acLDL), SPARC, and growth
      hormone family member placental lactogen (PL). At the same time, stabilin-1 is
      involved in trans-Golgi network-to-endosome routing of the endogenous chitinase
      like protein SI-CLP (stabilin-interacting chitinase-like protein). A DDSLL motif
      in the cytoplasmic tail of stabilin-1 interacts with GGA adaptors; however, the
      deletion of DDSLL reduces but does not abrogate this interaction. Here, we
      identified a novel GGA-binding site, EDDADDD, in the cytoplasmic tail of stabilin
      1. The deletion of EDDADDD impaired and the deletion of both the DDSLL and
      EDDADDD sites abrogated the interaction of stabilin-1 with GGAs. The surface
      exposure of stabilin-1 and stabilin-1-mediated endocytosis of acLDL, SPARC, and
      PL were not affected by the deletion either of DDSLL or EDDADDD or both. At the
      same time, both GGA-binding sites were necessary for the intracellular sorting of
      SI-CLP performed by stabilin-1. Our data indicate that the novel GGA-binding site
      EDDADDD is essential for stabilin-1-mediated intracellular sorting but is not
      required for endocytosis.

PMID- 19752196
TI  - Human ind1, an iron-sulfur cluster assembly factor for respiratory complex I.
AB  - Respiratory complex I (NADH:ubiquinone oxidoreductase) is a large mitochondrial
      inner membrane enzyme consisting of 45 subunits and 8 iron-sulfur (Fe/S)
      clusters. While complex I dysfunction is the most common reason for mitochondrial
      diseases, the assembly of complex I and its Fe/S cofactors remains elusive. Here,
      we identify the human mitochondrial P-loop NTPase, designated huInd1, that is
      critically required for the assembly of complex I. huInd1 can bind an Fe/S
      cluster via a conserved CXXC motif in a labile fashion. Knockdown of huInd1 in
      HeLa cells by RNA interference technology led to strong decreases in complex I
      protein and activity levels, remodeling of respiratory supercomplexes, and
      alteration of mitochondrial morphology. In addition, huInd1 depletion resulted in
      massive decreases in several subunits (NDUFS1, NDUFV1, NDUFS3, and NDUFA13) of
      the peripheral arm of complex I, with the concomitant appearance of a 450-kDa
      subcomplex representing part of the membrane arm. By a novel radiolabeling
      technique, the amount of iron associated with complex I was also shown to reflect
      the dependence of this enzyme on huInd1 for assembly. Together, these data
      identify huInd1 as a new assembly factor for human respiratory complex I with a
      possible role in the delivery of one or more Fe/S clusters to complex I subunits.

PMID- 19752198
TI  - Mutant huntingtin impairs vesicle formation from recycling endosomes by
      interfering with Rab11 activity.
AB  - Huntingtin (Htt) localizes to endosomes, but its role in the endocytic pathway is
      not established. Recently, we found that Htt is important for the activation of
      Rab11, a GTPase involved in endosomal recycling. Here we studied fibroblasts of
      healthy individuals and patients with Huntington's disease (HD), which is a
      movement disorder caused by polyglutamine expansion in Htt. The formation of
      endocytic vesicles containing transferrin at plasma membranes was the same in
      control and HD patient fibroblasts. However, HD fibroblasts were delayed in
      recycling biotin-transferrin back to the plasma membrane. Membranes of HD
      fibroblasts supported less nucleotide exchange on Rab11 than did control
      membranes. Rab11-positive vesicular and tubular structures in HD fibroblasts were
      abnormally large, suggesting that they were impaired in forming vesicles. We used
      total internal reflection fluorescence imaging of living fibroblasts to monitor
      fluorescence-labeled transferrin-carrying transport intermediates that emerged
      from recycling endosomes. HD fibroblasts had fewer small vesicles and more large
      vesicles and long tubules than did control fibroblasts. Dominant active Rab11
      expressed in HD fibroblasts normalized the recycling of biotin-transferrin. We
      propose a novel mechanism for cellular dysfunction by the HD mutation arising
      from the inhibition of Rab11 activity and a deficit in vesicle formation at
      recycling endosomes.

PMID- 19752199
TI  - Influence of the stereoisomeric position of the reactive acetate groups of the
      benzo[b]acronycine derivative S23906-1 on its DNA alkylation, helix-opening,
      cytotoxic, and antitumor activities.
AB  - S23906-1 is a benzo[b]acronycine derivative acting as a DNA-alkylating agent
      through covalent bonding to the exocyclic amino group of guanines and subsequent
      local opening of the DNA helix. This compound was selected for phase I clinical
      trials based on its efficient antitumor activity in experimental models and its
      unique mode of action. S23906-1 is the racemate of cis-1,2-diacetoxy-6-methoxy
      3,3,14-trimethyl-1,2,3,14-tetrahydro-7H-benzo[b]pyrano[3,2-h]acridin-7-one. Here,
      we evaluated the cytotoxic and antitumor activities of the two pure cis
      enantiomers and investigated the mechanism of action of both cis- and trans
      racemates and their enantiomers in terms of DNA alkylation potency and locally
      drug-induced DNA helix opening process. Reaction with glutathione, as a
      detoxification process, was also studied. The trans-compounds, both as racemate
      or separated enantiomers, were found less potent than the corresponding cis
      derivatives. Among the cis-enantiomers, the most efficient one regarding DNA
      alkylation bears the acetate on the reactive C1 position in the R configuration,
      both on purified DNA and genomic DNA extracted from cell cultures. By contrast,
      the most cytotoxic and tumor-active enantiomer bears the C1-acetate in the S
      configuration. Distinct cellular DNA-alkylation levels or covalent bonding to
      glutathione could not explain the differences. However, we showed that the S and
      R orientations of the acetate on C1 asymmetric carbon lead to different local
      opening of the DNA, as visualized using nuclease S1 mapping. These different
      interactions could lead to modulated DNA-repair, protein/DNA interaction, and
      apoptosis processes.

PMID- 19752200
TI  - Peroxisome proliferator-activated receptor gamma antagonists decrease Na+
      transport via the epithelial Na+ channel.
AB  - The epithelial sodium channel (ENaC) is believed to represent the rate-limiting
      step for sodium absorption in the renal collecting duct. Consequently, ENaC is a
      central effector affecting systemic blood volume and pressure. Sodium and water
      transport are dysregulated in diabetes mellitus. Peroxisome proliferator
      activated receptor gamma (PPARgamma) agonists are currently used in the treatment
      of type 2 diabetes, although their use remains limited by fluid retention. The
      effects of PPARgamma agonists on ENaC activity remain controversial. Although
      PPARgamma agonists were shown to stimulate ENaC-mediated renal salt absorption,
      probably via the serum- and glucocorticoid-regulated kinase 1, other studies
      reported that the PPARgamma agonist-induced fluid retention is independent of
      ENaC activity. Here we confirmed that four chemically distinct PPARgamma agonists
      [pioglitazone, rosiglitazone, troglitazone, and 15-deoxy-Delta12,14-prostaglandin
      J2 (PGJ2)] do not enhance Na+ transport in cultured renal collecting duct
      principal mpkCCDc14 cells, as assessed by short-circuit current measurements.
      However, the PPARgamma antagonist 2-chloro-5-nitro-N-4-pyridinyl-benzamide
      (T0070907), and to a lesser extent 2-chloro-5-nitrobenzanilide (GW9662), were
      found to decrease Na+ reabsorption across mpkCCDc14 cell layers. Furthermore,
      pretreatment of monolayers with T0070907 diminished the insulin-stimulated sodium
      transport. PPARgamma agonist PGJ2 did not enhance insulin-stimulated Na+ flux via
      ENaC. We also show that PPARgamma enhances ENaC activity when all three subunits
      are reconstituted in Chinese hamster ovary (CHO) cells. GW9662 inhibits ENaC
      activity when ENaC subunits are coexpressed in CHO cells with PPARgamma. In
      contrast, rosiglitazone has no effect on ENaC activity. We conclude that
      PPARgamma activity is important for maintaining basal and insulin-dependent
      transepithelial Na+ transport and ENaC activity.

PMID- 19752201
TI  - A Census-based longitudinal study of variations in survival amongst residents of
      nursing and residential homes in Northern Ireland.
AB  - BACKGROUND: despite the intensive services provided to residents of care homes,
      information on death rates is not routinely available for this population in the
      UK. OBJECTIVE: to quantify mortality rates across the care home population of
      Northern Ireland, and assess variation by type of care home and resident
      characteristics. DESIGN: a prospective, Census-based cohort study, with 5-year
      follow-up. PARTICIPANTS: all 9,072 residents of care homes for people aged 65 and
      over at the time of the 2001 census with a special emphasis on the 2,112
      residents admitted during the year preceding census day. MEASUREMENTS: age, sex,
      self-reported health, marital status, residence (not in care home, residential
      home, dual registered home, nursing home), elderly mentally infirm care
      provision. RESULTS: the median survival among nursing home residents was 2.33
      years (95% CI 2.25-2.59), for dual registered homes 2.75 (95% CI 2.42-3.17) and
      for residential homes 4.51 (95% CI 3.92-4.92) years. Age, sex and self-reported
      health showed weaker associations in the sicker populations in nursing homes
      compared to those in residential care or among the non-institutionalised.
      CONCLUSIONS: the high mortality in care homes indicates that places in care homes
      are reserved for the most severely ill and dependent. Death rates may not be an
      appropriate care quality measure for this population, but may serve as a useful
      adjunct for clinical staff and the planning of care home provision.

PMID- 19752202
TI  - Improving pain management in elderly patients with dementia: validation of the
      Doloshort observational pain assessment scale.

PMID- 19752203
TI  - The differential effects of forms and settings of exposure to violence on
      adolescents' adjustment.
AB  - This study investigated the link between exposure to violence and psychosocial
      adjustment for 442 Chinese secondary school students in Form 1-3. The students
      completed an inventory assessing exposure to violence through witnessing and
      through direct victimization in different settings (community, school, and home).
      Multiple measures and informants (i.e., self-report, teacher report, and school
      report) were used to assess emotional, behavioral, and cognitive functioning in
      adolescents. The results of this study showed that overall exposure to violence
      was related to emotional and behavior problems. High rates of exposure to
      violence across multiple contexts were found in this sample. After controlling
      for the co-occurrence of risk factors (e.g., exposure to violence in other
      settings), both witnessing school violence and being victimized by domestic
      violence were associated with emotional problems, whereas being victimized by
      community violence was related to behavior problems. These results suggest that
      there are differential effects of risks associated with different forms and
      settings of exposure.

PMID- 19752204
TI  - The long-term outcome of recurrent defects after rotator cuff repair.
AB  - BACKGROUND: Retears of the rotator cuff are not uncommon after arthroscopic and
      mini-open rotator cuff repairs. In most studies, the clinical results in patients
      with persistent defects demonstrated significantly less pain and better function
      and strength compared with their preoperative state at an early follow-up.
      HYPOTHESIS: The clinical and structural outcomes of patients with known rotator
      cuff defects will remain unchanged after a longer period of follow-up. STUDY
      DESIGN: Case series; Level of evidence, 4. METHODS: This study was performed in
      15 patients (18 shoulders) from a previous study who had recurrent rotator cuff
      defects 3.2 years after repair. Each patient completed the American Shoulder and
      Elbow Surgeons Scoring Survey, the Simple Shoulder Test, the L'Insalata Scoring
      Survey, and a visual analog scale for pain. Eleven patients (13 shoulders) were
      clinically reexamined at an average of 7.9 years for range of motion and
      strength, with targeted ultrasound. RESULTS: At the 7.9 year follow-up the
      average scores were 95 (American Shoulder and Elbow Surgeons), 95 (L'Insalata),
      11 (Simple Shoulder Test), and 0 (visual analog for pain), which were not
      statistically significantly different from the scores at 3.2 years. There was no
      change in the average range of motion; however, there was a statistically
      significant reduction in forward flexion strength and external rotation strength,
      as measured by a dynamometer. The average external rotation strength decreased by
      a mean of 42% and the mean forward flexion strength decreased by a mean of 45% (P
      < .001). Furthermore, there was a statistically significant increase in the mean
      size of the defect, from 273 mm(2) to 467 mm(2) (P < .001). Finally, the size of
      the defect increased in all patients, and no defects healed structurally.
      CONCLUSION: At an average of 7.9 years, patients with recurrent defects after
      rotator cuff repair still had an improvement in terms of pain, function, and
      satisfaction. However, the rotator cuff defect significantly increased in size,
      and there was a progression of strength deficits. These findings suggest that
      patients with recurrent defects can remain asymptomatic over the long term but
      will predictably lose strength in the involved extremity. Furthermore, the study
      demonstrated that defects after rotator cuff repair increase in size but often
      remain asymptomatic.

PMID- 19752206
TI  - Unusual cause of stroke in hypertrophic cardiomyopathy.

PMID- 19752207
TI  - Novel biomarkers for the diagnosis of acute destabilised heart failure in
      patients with shortness of breath.

PMID- 19752208
TI  - Strain rate evaluation of phasic atrial function in hypertension.

PMID- 19752209
TI  - Management of asymptomatic Wolff-Parkinson-White syndrome.

PMID- 19752210
TI  - Smoking cessation: how to advise the patient.

PMID- 19752211
TI  - Inhibition and stimulation of intestinal and hepatic CYP3A activity: studies in
      humanized CYP3A4 transgenic mice using triazolam.
AB  - CYP3A4 is an important determinant of drug-drug interactions. In this study, we
      evaluated whether cytochrome P450 3A knockout mice [Cyp3a(-/-)] and CYP3A4
      transgenic (CYP3A4-Tg) mice can be used to study drug-drug interactions in the
      liver and intestine. Triazolam was used as a probe drug because it is a highly
      specific CYP3A substrate and not a P-glycoprotein substrate. Triazolam metabolism
      was profoundly reduced in Cyp3a(-/-) mice both in vitro and in vivo. In vitro
      studies revealed clear species differences in humans and mice, but triazolam
      metabolism in microsomes derived from CYP3A4-Tg "humanized" mice closely
      resembled that in human microsomes. It is interesting to note that studies with
      tissue-specific CYP3A4-Tg mice revealed that intestinal CYP3A4 has a major impact
      on oral triazolam exposure, whereas the effect of hepatic CYP3A4 was limited. To
      mimic a drug-drug interaction, we coadministered triazolam with the prototypical
      CYP3A inhibitor ketoconazole, which increased triazolam exposure in all the CYP3A
      proficient mouse strains but not in Cyp3a(-/-) mice. We further found that the
      anticancer drug gefitinib is a potent stimulator of 1'-OH triazolam formation in
      vitro. It is noteworthy that we could also show in vivo stimulation of triazolam
      metabolism by gefitinib, resulting in a lower oral triazolam exposure. To our
      knowledge, this is the first in vivo example of direct stimulation of CYP3A4
      activity after oral drug administration. Overall, this study illustrates how
      Cyp3a(-/-) and CYP3A4-Tg mice can be used to study drug-drug interactions. The
      data clarify that for drugs that are not P-glycoprotein substrates, intestinal
      metabolism also can be more important than hepatic metabolism after oral
      administration.

PMID- 19752212
TI  - A promiscuous prion: efficient induction of [URE3] prion formation by
      heterologous prion domains.
AB  - The [URE3] and [PSI(+)] prions are the infections amyloid forms of the
      Saccharomyces cerevisiae proteins Ure2p and Sup35p, respectively. Randomizing the
      order of the amino acids in the Ure2 and Sup35 prion domains while retaining
      amino acid composition does not block prion formation, indicating that amino acid
      composition, not primary sequence, is the predominant feature driving [URE3] and
      [PSI(+)] formation. Here we show that Ure2p promiscuously interacts with various
      compositionally similar proteins to influence [URE3] levels. Overexpression of
      scrambled Ure2p prion domains efficiently increases de novo formation of wild
      type [URE3] in vivo. In vitro, amyloid aggregates of the scrambled prion domains
      efficiently seed wild-type Ure2p amyloid formation, suggesting that the wild-type
      and scrambled prion domains can directly interact to seed prion formation. To
      test whether interactions between Ure2p and naturally occurring yeast proteins
      could similarly affect [URE3] formation, we identified yeast proteins with
      domains that are compositionally similar to the Ure2p prion domain. Remarkably,
      all but one of these domains were also able to efficiently increase [URE3]
      formation. These results suggest that a wide variety of proteins could
      potentially affect [URE3] formation.

PMID- 19752213
TI  - TEN1 is essential for CDC13-mediated telomere capping.
AB  - Telomere binding proteins protect chromosome ends from degradation and mask
      chromosome termini from checkpoint surveillance. In Saccharomyces cerevisiae,
      Cdc13 binds single-stranded G-rich telomere repeats, maintaining telomere
      integrity and length. Two additional proteins, Ten1 and Stn1, interact with Cdc13
      but their contributions to telomere integrity are not well defined. Ten1 is known
      to prevent accumulation of aberrant single-stranded telomere DNA; whether this
      results from defective end protection or defective telomere replication is
      unclear. Here we report our analysis of a new group of ten1 temperature-sensitive
      (ts) mutants. At permissive temperatures, ten1-ts strains display greatly
      elongated telomeres. After shift to nonpermissive conditions, however, ten1-ts
      mutants accumulate extensive telomeric single-stranded DNA. Cdk1 activity is
      required to generate these single-stranded regions, and deleting the EXO1
      nuclease partially suppresses ten1-ts growth defects. This is similar to cdc13-1
      mutants, suggesting ten1-ts strains are defective for end protection. Moreover,
      like Cdc13, our analysis reveals Ten1 promotes de novo telomere addition.
      Interestingly, in ten1-ts strains at high temperatures, telomeric single-stranded
      DNA and Rad52-YFP repair foci are strongly induced despite Cdc13 remaining
      associated with telomeres, revealing Cdc13 telomere binding is not sufficient for
      end protection. Finally, unlike cdc13-1 mutants, ten1-ts strains display strong
      synthetic interactions with mutations in the POLalpha complex. These results
      emphasize that Cdc13 relies on Ten1 to execute its essential function, but leave
      open the possibility that Ten1 has a Cdc13-independent role in DNA replication.

PMID- 19752214
TI  - Interlock formation and coiling of meiotic chromosome axes during synapsis.
AB  - The meiotic prophase chromosome has a unique architecture. At the onset of
      leptotene, the replicated sister chromatids are organized along an axial element.
      During zygotene, as homologous chromosomes pair and synapse, a synaptonemal
      complex forms via the assembly of a transverse element between the two axial
      elements. However, due to the limitations of light and electron microscopy,
      little is known about chromatin organization with respect to the chromosome axes
      and about the spatial progression of synapsis in three dimensions. Three
      dimensional structured illumination microscopy (3D-SIM) is a new method of
      superresolution optical microscopy that overcomes the 200-nm diffraction limit of
      conventional light microscopy and reaches a lateral resolution of at least 100
      nm. Using 3D-SIM and antibodies against a cohesin protein (AFD1/REC8), we
      resolved clearly the two axes that form the lateral elements of the synaptonemal
      complex. The axes are coiled around each other as a left-handed helix, and AFD1
      showed a bilaterally symmetrical pattern on the paired axes. Using the
      immunostaining of the axial element component (ASY1/HOP1) to find unsynapsed
      regions, entangled chromosomes can be easily detected. At the late zygotene/early
      pachytene transition, about one-third of the nuclei retained unsynapsed regions
      and 78% of these unsynapsed axes were associated with interlocks. By late
      pachytene, no interlocks remain, suggesting that interlock resolution may be an
      important and rate-limiting step to complete synapsis. Since interlocks are
      potentially deleterious if left unresolved, possible mechanisms for their
      resolution are discussed in this article.

PMID- 19752215
TI  - Stall encodes an ADAMTS metalloprotease and interacts genetically with Delta in
      Drosophila ovarian follicle formation.
AB  - Ovarian follicle formation in Drosophila melanogaster requires stall (stl) gene
      function, both within and outside the ovary, for follicle individualization,
      stalk cell intercalation, and oocyte localization. We have identified the stl
      transcript as CG3622 and confirmed the presence of three alternatively spliced
      isoforms, contrary to current genome annotation. Here we show that the gene is
      expressed in both ovarian and brain tissues, which is consistent with previous
      evidence of an ovary nonautonomous function. On the basis of amino acid sequence,
      stl encodes a metalloprotease similar to the "a disintegrin and metalloprotease
      with thrombospondin" (ADAMTS) family. Although stl mutant ovaries fail to
      maintain the branched structure of the fusome and periodically show improperly
      localized oocytes, stl mutants do not alter oocyte determination. Within the
      ovary, stl is expressed in pupal basal stalks and in adult somatic cells of the
      posterior germarium and the follicular poles. Genetically, stl exhibits a strong
      mutant interaction with Delta (Dl), and Dl mutant ovaries show altered stl
      expression patterns. Additionally, a previously described genetic interactor,
      daughterless, also modulates stl expression in the somatic ovary and may do so
      directly in its capacity as a basic helix-loop-helix (bHLH) transcription factor.
      We propose a complex model of long-range extraovarian signaling through secretion
      or extracellular domain shedding, together with local intraovarian protein
      modification, to explain the dual sites of Stl metalloprotease function in
      oogenesis.

PMID- 19752216
TI  - A combinatorial interplay among the 1-aminocyclopropane-1-carboxylate isoforms
      regulates ethylene biosynthesis in Arabidopsis thaliana.
AB  - Ethylene (C(2)H(4)) is a unique plant-signaling molecule that regulates numerous
      developmental processes. The key enzyme in the two-step biosynthetic pathway of
      ethylene is 1-aminocyclopropane-1-carboxylate synthase (ACS), which catalyzes the
      conversion of S-adenosylmethionine (AdoMet) to ACC, the precursor of ethylene. To
      understand the function of this important enzyme, we analyzed the entire family
      of nine ACS isoforms (ACS1, ACS2, ACS4-9, and ACS11) encoded in the Arabidopsis
      genome. Our analysis reveals that members of this protein family share an
      essential function, because individual ACS genes are not essential for
      Arabidopsis viability, whereas elimination of the entire gene family results in
      embryonic lethality. Phenotypic characterization of single and multiple mutants
      unmasks unique but overlapping functions of the various ACS members in plant
      developmental events, including multiple growth characteristics, flowering time,
      response to gravity, disease resistance, and ethylene production. Ethylene acts
      as a repressor of flowering by regulating the transcription of the FLOWERING
      LOCUS C. Each single and high order mutant has a characteristic molecular
      phenotype with unique and overlapping gene expression patterns. The expression of
      several genes involved in light perception and signaling is altered in the high
      order mutants. These results, together with the in planta ACS interaction map,
      suggest that ethylene-mediated processes are orchestrated by a combinatorial
      interplay among ACS isoforms that determines the relative ratio of homo- and
      heterodimers (active or inactive) in a spatial and temporal manner. These subunit
      isoforms comprise a combinatorial code that is a central regulator of ethylene
      production during plant development. The lethality of the null ACS mutant
      contrasts with the viability of null mutations in key components of the ethylene
      signaling apparatus, strongly supporting the view that ACC, the precursor of
      ethylene, is a primary regulator of plant growth and development.

PMID- 19752217
TI  - In planta mutagenesis determines the functional regions of the wheat puroindoline
      proteins.
AB  - In planta analysis of protein function in a crop plant could lead to improvements
      in understanding protein structure/function relationships as well as selective
      agronomic or end product quality improvements. The requirements for successful in
      planta analysis are a high mutation rate, an efficient screening method, and a
      trait with high heritability. Two ideal targets for functional analysis are the
      Puroindoline a and Puroindoline b (Pina and Pinb, respectively) genes, which
      together compose the wheat (Triticum aestivum L.) Ha locus that controls grain
      texture and many wheat end-use properties. Puroindolines (PINs) together impart
      soft texture, and mutations in either PIN result in hard seed texture. Studies of
      the PINs' mode of action are limited by low allelic variation. To create new Pin
      alleles and identify critical function-determining regions, Pin point mutations
      were created in planta via EMS treatment of a soft wheat. Grain hardness of 46
      unique PIN missense alleles was then measured using segregating F(2):F(3)
      populations. The impact of individual missense alleles upon PIN function, as
      measured by grain hardness, ranged from neutral (74%) to intermediate to function
      abolishing. The percentage of function-abolishing mutations among mutations
      occurring in both PINA and PINB was higher for PINB, indicating that PINB is more
      critical to overall Ha function. This is contrary to expectations in that PINB is
      not as well conserved as PINA. All function-abolishing mutations resulted from
      structure-disrupting mutations or from missense mutations occurring near the
      Tryptophan-rich region. This study demonstrates the feasibility of in planta
      functional analysis of wheat proteins and that the Tryptophan-rich region is the
      most important region of both PINA and PINB.

PMID- 19752218
TI  - The sheltered genetic load linked to the s locus in plants: new insights from
      theoretical and empirical approaches in sporophytic self-incompatibility.
AB  - Inbreeding depression and mating systems evolution are closely linked, because
      the purging of deleterious mutations and the fitness of individuals may depend on
      outcrossing vs. selfing rates. Further, the accumulation of deleterious mutations
      may vary among genomic regions, especially for genes closely linked to loci under
      balancing selection. Sporophytic self-incompatibility (SSI) is a common genetic
      mechanism in angiosperm that enables hermaphrodite plants to avoid selfing and
      promote outcrossing. The SSI phenotype is determined by the S locus and may
      depend on dominance relationships among alleles. Since most individuals are
      heterozygous at the S locus and recombination is suppressed in the S-locus
      region, it has been suggested that deleterious mutations could accumulate at
      genes linked to the S locus, generating a "sheltered load." In this article, we
      first theoretically investigate the conditions generating sheltered load in SSI.
      We show that deleterious mutations can accumulate in linkage with specific S
      alleles, and particularly if those S alleles are dominant. Second, we looked for
      the presence of sheltered load in Arabidopsis halleri using CO(2) gas treatment
      to overcome self-incompatibility. By examining the segregation of S alleles and
      measuring the relative fitness of progeny, we found significant sheltered load
      associated with the most dominant S allele (S15) of three S alleles tested. This
      sheltered load seems to be expressed at several stages of the life cycle and to
      have a larger effect than genomic inbreeding depression.

PMID- 19752219
TI  - Insulin receptor isoforms and insulin receptor/insulin-like growth factor
      receptor hybrids in physiology and disease.
AB  - In mammals, the insulin receptor (IR) gene has acquired an additional exon, exon
      11. This exon may be skipped in a developmental and tissue-specific manner. The
      IR, therefore, occurs in two isoforms (exon 11 minus IR-A and exon 11 plus IR-B).
      The most relevant functional difference between these two isoforms is the high
      affinity of IR-A for IGF-II. IR-A is predominantly expressed during prenatal
      life. It enhances the effects of IGF-II during embryogenesis and fetal
      development. It is also significantly expressed in adult tissues, especially in
      the brain. Conversely, IR-B is predominantly expressed in adult, well
      differentiated tissues, including the liver, where it enhances the metabolic
      effects of insulin. Dysregulation of IR splicing in insulin target tissues may
      occur in patients with insulin resistance; however, its role in type 2 diabetes
      is unclear. IR-A is often aberrantly expressed in cancer cells, thus increasing
      their responsiveness to IGF-II and to insulin and explaining the cancer-promoting
      effect of hyperinsulinemia observed in obese and type 2 diabetic patients.
      Aberrant IR-A expression may favor cancer resistance to both conventional and
      targeted therapies by a variety of mechanisms. Finally, IR isoforms form
      heterodimers, IR-A/IR-B, and hybrid IR/IGF-IR receptors (HR-A and HR-B). The
      functional characteristics of such hybrid receptors and their role in physiology,
      in diabetes, and in malignant cells are not yet fully understood. These receptors
      seem to enhance cell responsiveness to IGFs.

PMID- 19752221
TI  - Furin-processed antigens targeted to the secretory route elicit functional TAP1-/
      CD8+ T lymphocytes in vivo.
AB  - Most pathogen-derived peptides recognized by CD8+ CTL are produced by proteasomes
      and delivered to the endoplasmic reticulum by the TAP transporters associated
      with Ag processing. Alternative proteases also produce antigenic peptides, but
      their actual relevance is unclear. There is a need to quantify the contribution
      of these supplementary pathways in vitro and in vivo. A well-defined TAP
      independent secretory route of Ag processing involves the trans-Golgi network
      protease furin. Quantitation of this route by using OVA constructs encoded by
      vaccinia viruses indicates that it provides approximately one-third of all
      surface complexes of peptide and MHC class I molecules. Generation of the epitope
      carboxyl terminus is a dramatic rate-limiting step, since bypassing it increased
      efficiency by at least 1000-fold. Notably, the secretory construct activated a
      similar percentage of Ag-specific CD8+ T cells in wild type as in TAP1-deficient
      mice, which allow only secretory routes but which have a 10- to 20-fold smaller
      CD8 compartment. Moreover, these TAP1(-/-) OVA-specific CD8+ T lymphocytes
      accomplished elimination of epitope-bearing cells in vivo. The results obtained
      with this experimental system underscore the potential of secretory pathways of
      MHC class I Ag presentation to elicit functional CD8+ T lymphocytes in vivo and
      support the hypothesis that noncytosolic processing mechanisms may compensate in
      vivo for the lack of proteasome participation in Ag processing in persons
      genetically deficient in TAP and thus contribute to pathogen control.

PMID- 19752220
TI  - Efficient cross-priming of antiviral CD8+ T cells by antigen donor cells is GRP94
      independent.
AB  - Cross-priming, the activation of naive CD8+ T cells by dendritic cells presenting
      Ags synthesized by other cells, is believed to play an important role in the
      generation of antiviral and antitumor responses. The molecular mechanism(s)
      underlying cross-priming remain poorly defined and highly controversial. GRP94
      (gp96), an abundant endoplasmic reticulum chaperone with innate immune-activating
      capacity, has been widely reported to play a major role in cross-priming. In this
      study, we show that cells whose expression of GRP94 is silenced via transient or
      stable transfection with GRP94-directed small interfering RNAs demonstrate no
      reduction in their abilities to generate class I peptide complexes in cultured
      cells or to prime antiviral CD8+ T cell responses in vivo. In demonstrating the
      dispensability of GRP94, our finding points to the importance of alternative
      mechanisms for generation of class I peptide complexes from endogenous and
      exogenous Ags and immunogens.

PMID- 19752222
TI  - A role for complement in the enhanced susceptibility of steatotic livers to
      ischemia and reperfusion injury.
AB  - Hepatic steatosis typically renders the donor organ unusable, as donor organs
      with >30% steatosis are more likely to develop graft failure. The mechanisms
      leading to failure are not well defined, but steatosis enhances hepatic
      susceptibility to ischemia reperfusion injury (IRI). We investigated the role of
      complement in hepatic IRI in lean and steatotic (diet-induced) mice. Steatotic
      mice were significantly more susceptible to total warm hepatic IRI than lean mice
      as determined by serum alanine aminotransferase, histopathologically assessed
      damage, and 24-h survival. C3 deficiency protected both lean and steatotic mice
      from IRI, as determined by all measured outcomes. Furthermore, treatment of wild
      type mice with the complement inhibitor CR2-Crry provided protection equivalent
      to that seen in C3-deficient mice. Importantly, although steatotic livers were
      much more susceptible to IRI than lean livers, by most measures there was no
      statistical difference between the level of IRI to steatotic or lean livers when
      complement was inhibited. To investigate the clinical relevance of these findings
      in the context of transplantation, we treated recipients of lean or steatotic
      liver grafts with saline or CR2-Crry. There was a marked reduction in graft
      inflammation and injury and significantly improved 7-day survival in CR2-Crry
      treated recipients of either lean or steatotic grafts. These data indicate that
      complement plays a key role in the enhanced susceptibility of steatotic livers to
      IRI and suggest that complement inhibition represents a potential strategy to
      reduce the donor shortage by allowing the more routine use of marginal steatotic
      donor livers.

PMID- 19752223
TI  - CRTAM confers late-stage activation of CD8+ T cells to regulate retention within
      lymph node.
AB  - In vivo immune response is triggered in the lymph node, where lymphocytes for
      entry into, retention at, and migration to effector sites are dynamically
      regulated. The molecular mechanism underlying retention regulation is the key to
      elucidating in vivo regulation of immune response. In this study, we describe the
      function of the adhesion molecule class I-restricted T cell-associated molecule
      (CRTAM) in regulating CD8+ T cell retention within the lymph node and eventually
      effector function. We previously identified CRTAM as a receptor predominantly
      expressed on activated CD8+ T cells, and nectin-like molecule-2 (Necl2) as its
      ligand. In vivo function of CRTAM-Necl2 interaction was analyzed by generating
      CRTAM(-/-) mice. CRTAM(-/-) mice exhibited reduced protective immunity against
      viral infection and impaired autoimmune diabetes induction in vivo. Although Ag
      specific CRTAM(-/-) CD8+ T cells showed normal CTL functions in vitro, their
      number in the draining lymph node was reduced. Because CRTAM+ T cells bound
      efficiently to Necl2-expressing CD8+ dendritic cells (DCs) that reside in T cell
      area of lymph node, CRTAM may induce retention by binding to CD8+ DCs at the late
      stage of activation before proliferation. The CRTAM-mediated late interaction
      with DCs induced retention of activated CD8+ T cells in an Ag-independent
      fashion, and this possibly resulted in effective CTL development in the draining
      lymph node.

PMID- 19752224
TI  - T cell infiltrates in the muscles of patients with dermatomyositis and
      polymyositis are dominated by CD28null T cells.
AB  - Dermatomyositis and polymyositis are disabling rheumatic diseases characterized
      by an appreciable number of T cells infiltrating muscle tissue. The precise
      phenotype, function and specificity of these cells remain elusive. In this study,
      we aimed to characterize T cells in muscle tissue and circulation and to
      investigate their association to clinical phenotype. Twenty-four patients with
      dermatomyositis and 42 with polymyositis were screened for frequency of
      CD4+CD28(null) and CD8+CD28(null) T cells in peripheral blood by flow cytometry.
      Presence of these cells in inflamed muscle tissue from 13 of these patients was
      analyzed by three-color immunofluorescence microscopy. Effector functions,
      proliferation and Ag specificity were analyzed by flow cytometry after in vitro
      stimulation. The clinical relevance of CD28(null) T cells was analyzed by
      multiple regression analyses including six separate and combined disease
      variables. We demonstrate that muscle-infiltrating T cells are predominantly
      CD4+CD28(null) and CD8+CD28(null) T cells in patients with dermatomyositis and
      polymyositis. Muscle-infiltrating CD28(null) T cells were found already at time
      of diagnosis. Disease activity correlated with the frequency of CD8+ T cells in
      the inflamed muscles of polymyositis patients. Circulating CD4+CD28(null) and
      CD8+CD28(null) T cells were significantly more frequent in human CMV (HCMV)
      seropositive individuals, responded to HCMV Ag stimulation, and correlated with
      disease duration. These cells also display a proinflammatory cytokine profile,
      contain perforin and lack the costimulatory molecule CD28. Our observations imply
      that CD28(null) T cells represent clinically important effector cells in
      dermatomyositis and polymyositis, and that HCMV might play a role in propagating
      disease in a subset of patients.

PMID- 19752225
TI  - The role of macrophage-derived IL-1 in induction and maintenance of angiogenesis.
AB  - Inflammation and angiogenesis are pivotal processes in the progression of many
      diseases, including malignancies. A hypoxic microenvironment often results in a
      milieu of proinflammatory and proangiogenic cytokines produced by infiltrating
      cells. We assessed the role of macrophage-derived hypoxia-associated cytokines in
      promoting inflammation and angiogenesis. Supernatants of macrophages, stimulated
      under hypoxia with or without an inflammatory stimulus (LPS), promoted
      angiogenesis when incorporated into Matrigel plugs. However, neutralization of IL
      1 in the supernatants, particularly IL-1beta, completely abrogated cell
      infiltration and angiogenesis in Matrigel plugs and reduced vascular endothelial
      growth factor (VEGF) levels by 85%. Similarly, supernatants from macrophages of
      IL-1beta knockout mice did not induce inflammatory or angiogenic responses. The
      importance of IL-1 signaling in the host was demonstrated by the dramatic
      reduction of inflammatory and angiogenic responses in Matrigel plugs that
      contained macrophage supernatants from control mice which had been implanted in
      IL-1 receptor type I knockout mice. Myeloid cells infiltrating into Matrigel
      plugs were of bone marrow origin and represented the major source of IL-1 and
      other cytokines/chemokines in the plugs. Cells of endothelial lineage were the
      main source of VEGF and were recruited mainly from neighboring tissues, rather
      than from the bone marrow. Using the aortic ring sprouting assay, it was shown
      that in this experimental system, IL-1 does not directly activate endothelial
      cell migration, proliferation and organization into blood vessel-like structures,
      but rather activates infiltrating cells to produce endothelial cell activating
      factors, such as VEGF. Thus, targeting IL-1beta has the potential to inhibit
      angiogenesis in pathological situations and may be of considerable clinical
      value.

PMID- 19752226
TI  - Regulatory T cells negatively regulate neovasculature of airway remodeling via
      DLL4-Notch signaling.
AB  - Regulatory T cells (Treg) have been shown to prevent the development of allergic
      asthma; however, the role of Treg in asthma with established airway remodeling is
      unknown. To address this, we exploited an OVA-induced chronic asthma mouse model
      wherein Treg were adoptively transferred to the mice at chronic stage of the
      model. We found that among the structural alterations of airway remodeling, Treg
      selectively reduced the vessel numbers in both peritracheal and peribronchial
      regions and the lung parenchyma. Extracellular matrix deposition, mucus
      metaplasia, muscular hyperplasia, and vasodilation, as were also induced by
      chronic allergen challenge, were not affected by Treg. TUNEL staining of the lung
      sections revealed an increased endothelial cell (EC) apoptosis in mice receiving
      Treg transfers compared with their asthmatic counterparts. By using Matrigel
      angiogenesis assays, we showed that Treg inhibited EC angiogenesis both in vitro
      and in vivo. Treg preferentially expressed Notch ligand DLL4, and an anti-DLL4
      blocking Ab abrogated the inhibitory effect of Treg on EC tube formation. In
      vivo, decreased airway and lung vessel numbers as well as ameliorated airway
      hyperresponsiveness after Treg transfers were reverted when Treg-derived DLL4
      signal was blocked by the anti-DLL4 Ab. Our findings demonstrate a novel function
      of Treg whereby Treg down-regulate remodeling angiogenesis via proapoptotic DLL4
      Notch signaling, and suggest a therapeutic potential of Treg in alleviating
      airway hyperresponsiveness of chronic asthma.

PMID- 19752227
TI  - The immunological impact of genetic drift in the B10.BR congenic inbred mouse
      strain.
AB  - The MHC-matched, minor histocompatibility Ag (miHA)-mismatched B10.BR-->CBA
      strain combination has been used to elucidate the immunobiology of graft-vs-host
      disease (GVHD) following allogeneic bone marrow transplantation. Studies
      conducted in the 1980s had established that B10.BR CD8+ T cells were capable of
      mediating GVHD in the absence of CD4+ T cells, and that CD4+ T cells were unable
      to induce lethal disease. In more recent studies with this GVHD model, we
      detected etiological discrepancies with the previously published results, which
      suggested that genetic drift might have occurred within the B10.BR strain. In
      particular, there was increased allorecognition of CBA miHA by B10.BR CD4+ T
      cells, as determined by both TCR Vbeta spectratype analysis and the induction of
      lethal GVHD in CBA recipients. Additionally, alloreactivity was observed between
      the genetically drifted mice (B10.BR/Jdrif) and mice rederived from frozen
      embryos of the original strain (B10.BR/Jrep) using Vbeta spectratype analysis and
      IFN-gamma ELISPOT assays, suggesting that new miHA differences had arisen between
      the mice. Furthermore, T cell-depleted B10.BR/Jdrif bone marrow cells were unable
      to provide long-term survival following either allogeneic or syngeneic bone
      marrow transplantation. Gene expression analysis revealed several genes involved
      in hematopoiesis that were overexpressed in the lineage-negative fraction of
      B10.BR/Jdrif bone marrow, as compared with B10.BR/Jrep mice. Taken together,
      these results suggest that genetic drift in the B10.BR strain has significantly
      impacted the immune alloreactive response in the GVHD model by causing altered
      expression of miHA and diminished capacity for survival following transplantation
      into lethally irradiated recipients.

PMID- 19752228
TI  - MS4A4B is a GITR-associated membrane adapter, expressed by regulatory T cells,
      which modulates T cell activation.
AB  - In the aftermath of thymic negative selection, natural and adaptive regulatory T
      cells (Tregs) must acknowledge peripheral, "danger-free" self-Ag to ensure their
      sustained activity. In this paper, we show that natural and adaptive Tregs or T
      cells transduced with cDNA for Foxp3, just like Th1 cells, express members of the
      MS4A family of transmembrane molecules. Naive T cells transduced with MS4A4B
      become able to respond to lower levels of Ag. Using two family members, MS4A4B
      and MS4A6B, as baits in a yeast split-ubiquitin Treg library screen, we
      demonstrate their interaction with each other and with GITR, Orai1, and other
      surface receptors. Interaction of 4B with GITR augments GITR signaling and T cell
      IL-2 production in response to triggering with GITR ligand or anti-GITR Abs. This
      interaction provides a mechanism whereby MS4A family members, through lateral
      coassociation with costimulatory molecules, may amplify Ag signals. We propose
      that T cells preoccupied with immune defense use this MS4A family to enhance
      sensitivity to extrinsic Ag stimulation, ensuring its elimination, while Tregs
      use these adaptors to allow low level Ag signals to sustain regulatory function.

PMID- 19752229
TI  - Aldose reductase inhibition suppresses the expression of Th2 cytokines and airway
      inflammation in ovalbumin-induced asthma in mice.
AB  - Airway inflammation induced by reactive oxygen species-mediated activation of
      redox-sensitive transcription factors is the hallmark of asthma, a prevalent
      chronic respiratory disease. In various cellular and animal models, we have
      recently demonstrated that, in response to multiple stimuli, aldose reductase
      (AR) regulates the inflammatory signals mediated by NF-kappaB. Because NF-kappaB
      mediated inflammation is a major characteristic of asthma pathogenesis, we have
      investigated the effect of AR inhibition on NF-kappaB and various inflammatory
      markers in cellular and animal models of asthma using primary human small airway
      epithelial cells and OVA-sensitized/challenged C57BL/6 mice, respectively. We
      observed that pharmacological inhibition or genetic ablation of AR by small
      interfering RNA prevented TNF-alpha- as well as LPS-induced apoptosis; reactive
      oxygen species generation; synthesis of inflammatory markers IL-6, IL-8, and
      PGE(2); and activation of NF-kappaB and AP-1 in small airway epithelial cells. In
      OVA-challenged mice, we observed that administration of an AR inhibitor markedly
      reduced airway hyperresponsiveness, IgE levels, eisonophils infiltration, and
      release of Th2 type cytokines in the airway. Our results indicate that AR
      inhibitors may offer a novel therapeutic approach to treat inflammatory airway
      diseases such as asthma.

PMID- 19752230
TI  - Genomic and functional uniqueness of the TNF receptor-associated factor gene
      family in amphioxus, the basal chordate.
AB  - The TNF-associated factor (TRAF) family, the crucial adaptor group in innate
      immune signaling, increased to 24 in amphioxus, the oldest lineage of the
      Chordata. To address how these expanded molecules evolved to adapt to the
      changing TRAF mediated signaling pathways, here we conducted genomic and
      functional comparisons of four distinct amphioxus TRAF groups with their human
      counterparts. We showed that lineage-specific duplication and rearrangement were
      responsible for the expansion of amphioxus TRAF1/2 and 3 lineages, whereas TRAF4
      and 6 maintained a relatively stable genome and protein structure. Amphioxus
      TRAF1/2 and 3 molecules displayed various expression patterns in response to
      microbial infection, and some of them can attenuate the NF-kappaB activation
      mediated by human TRAF2 and 6. Amphioxus TRAF4 presented two unique functions:
      activation of the NF-kappaB pathway and involvement in somite formation. Although
      amphioxus TRAF6 was conserved in activating NF-kappaB pathway for antibacterial
      defense, the mechanism was not the same as that observed in humans. In summary,
      our findings reveal the evolutionary uniqueness of the TRAF family in this basal
      chordate, and suggest that genomic duplication and functional divergence of the
      TRAF family are important for the current form of the TRAF-mediated signaling
      pathways in humans.

PMID- 19752232
TI  - Bacterial surface protein L binds and inactivates neutrophil proteins S100A8/A9.
AB  - Finegoldia magna is an anaerobic bacterial species that is part of the normal
      human flora on all nonsterile body surfaces, but it is also a significant
      opportunistic pathogen causing a wide range of infections. Some isolates of F.
      magna that are more frequently associated with clinical infection express protein
      L, a surface protein containing multiple homologous domains (B1-B5) that bind Igs
      through interactions with Ig L chains. The present study shows that the N
      terminal A domain of protein L binds S100A8/A9, antibacterial proteins present in
      large amounts in the cytoplasm of neutrophils, but also extracellularly in
      tissues during inflammation. As a result, protein L-expressing F. magna are
      protected against killing by S100A8/A9. Igs and S100A8/A9 were found to interact
      independently with protein L, demonstrating that this bacterial surface protein
      is capable of manipulating both adaptive and innate immune defense mechanisms.

PMID- 19752231
TI  - Dimorphic motifs in D0 and D1+D2 domains of killer cell Ig-like receptor 3DL1
      combine to form receptors with high, moderate, and no avidity for the complex of
      a peptide derived from HIV and HLA-A*2402.
AB  - Comparison of mutant killer cell Ig-like receptor (KIR) 3DL1*015 substituted at
      natural positions of variation showed that tryptophan/leucine dimorphism at
      position 283 uniquely changes receptor conformation and can strongly influence
      binding of the A24nef tetramer. Dimorphic motifs at positions 2, 47, and 54 in D0
      and 182 and 283 in D1+D2 distinguish the two 3DL1 lineages, typified by 3DL1*005
      and 3DL1*015. The interlineage recombinant, KIR3DL1*001, combines D0 of 3DL1*005
      with D1+D2 of 3DL1*015 and binds A24nef more strongly than either parent. In
      contrast, the reciprocal recombinant with D0 from 3DL1*015 and D1+D2 from
      3DL1*005 cannot bind A24nef. Thus, D0 polymorphism directly affects the avidity
      of the KIR3DL1 ligand binding site. From these observations, multiple sequence
      alignment, and homology modeling, we constructed structural models for KIR3DL1
      and its complex with A24nef. In these models, D0, D1, and D2 come together to
      form a binding surface for A24nef, which is contacted by all three Ig-like
      domains. A central pocket binds arginine 83, the only Bw4 motif residue essential
      for KIR3DL1 interaction, similar to the binding of lysine 80 in HLA-C by KIR2DL1.
      Central to this interaction is a salt bridge between arginine 83 of Bw4 and
      glutamate 282 of 3DL1, which juxtaposes the functionally influential dimorphism
      at position 283. Further 3DL1 mutants were tested and shown to have A24nef
      binding properties consistent with the models. A24nef was not bound by KIR3DS1,
      the activating counterpart of KIR3DL1. Moreover, introducing any one of three
      residues specific to KIR3DS1, serine 163, arginine 166, or leucine 199, into
      3DL1*015, abrogated A24nef binding.

PMID- 19752233
TI  - Improved survival and reduced vascular permeability by eliminating or blocking
      12/15-lipoxygenase in mouse models of acute lung injury (ALI).
AB  - Acute lung injury (ALI) is a prevalent disease associated with high mortality.
      12/15-lipoxygenase (12/15-LO) is an enzyme producing 12-hydroxyeicosatetraenoic
      acid (HETE) and 15-HETE from arachidonic acid. To test whether 12/15-LO is
      involved in increasing vascular permeability in the lung, we investigated the
      role of 12/15-LO in murine models of LPS-induced pulmonary inflammation and
      clinically relevant acid-induced ALI. The vascular permeability increase upon LPS
      inhalation was abolished in Alox15(-/-) mice lacking 12/15-LO and in wild-type
      mice after pharmacological blockade of 12/15-LO. Alox15(-/-) mice also showed
      improved gas exchange, reduced permeability increase, and prolonged survival in
      the acid-induced ALI model. Bone marrow chimeras and reconstitution experiments
      revealed that 12-HETE produced by hematopoietic cells regulates vascular
      permeability through a CXCR2-dependent mechanism. Our findings suggest that 12/15
      LO-derived 12-HETE is a key mediator of vascular permeability in acute lung
      injury.

PMID- 19752234
TI  - Human mast cells adhere to and migrate on epithelial and vascular basement
      membrane laminins LM-332 and LM-511 via alpha3beta1 integrin.
AB  - Mast cells (MCs) are multifunctional effectors of the immune system that are
      distributed in many tissues, often in close association with the basement
      membrane of blood vessels, epithelium and nerves. Laminins (LMs), a family of
      large alphabetagamma heterotrimeric proteins, are major components of basement
      membrane that strongly promote cell adhesion and migration. In this study, we
      investigated the role of LM isoforms and their integrin receptors in human MC
      biology in vitro. In functional assays, alpha3-(LM-332) and alpha5-(LM-511) LMs,
      but not alpha1-(LM-111), alpha2-(LM-211), or alpha4-(LM-411) LMs, readily
      promoted adhesion and migration of cultured MCs. These activities were strongly
      enhanced by various stimuli. alpha3-LM was also able to costimulate IL-8
      production. Among LM-binding integrins, MCs expressed alpha(3)beta(1), but not
      alpha(6)beta(1), alpha(7)beta(1), or alpha(6)beta(4), integrins. Blocking Abs to
      alpha(3)beta(1) integrin caused inhibition of both cell adhesion and migration on
      alpha3- and alpha5-LMs. Immunohistochemical studies on skin showed that MCs
      colocalized with epithelial and vascular basement membranes that expressed alpha3
      and alpha5-LMs and that MCs expressed alpha(3) integrin but not alpha(6)
      integrin(s). These results demonstrate a role for alpha3- and alpha5-LMs and
      their alpha(3)beta(1) integrin receptor in MC biology. This may explain the
      intimate structural and functional interactions that MCs have with specific
      basement membranes.

PMID- 19752235
TI  - IL-13-induced oxidative stress via microglial NADPH oxidase contributes to death
      of hippocampal neurons in vivo.
AB  - In the present study, we investigated the effects of IL-13, a well-known anti
      inflammatory cytokine, on the thrombin-treated hippocampus in vivo. NeuN
      immunohistochemistry and Nissl staining revealed significant loss of hippocampal
      CA1 neurons upon intrahippocampal injection of thrombin. This neurotoxicity was
      accompanied by substantial microglial activation, as evident from OX-42
      immunohistochemistry results. In parallel, Western blot analysis and
      hydroethidine histochemistry disclosed activation of NADPH oxidase, generation of
      reactive oxygen species, and oxidative damage in the hippocampal CA1 area showing
      hippocampal neuron degeneration. Interestingly, immunohistochemical and
      biochemical experiments showed that intrahippocampal injection of thrombin
      increased IL-13 immunoreactivity and IL-13 levels as early as 8 h after thrombin,
      reaching a peak at 7 days, which was maintained up to 14 days. Moreover, double
      label immunohistochemistry revealed IL-13 immunoreactivity exclusively in
      activated microglia. IL-13-neutralizing Abs significantly rescued CA1 hippocampal
      neurons from thrombin neurotoxicity. In parallel, neutralization of IL-13
      inhibited activation of NADPH oxidase, reactive oxygen species production, and
      oxidative damage. Additionally, IL-13 neutralization suppressed the expression of
      inducible NO synthase and several proinflammatory cytokines. To our knowledge,
      the present study is the first to show that IL-13 triggers microglial NADPH
      oxidase-derived oxidative stress, leading to the degeneration of hippocampal
      neurons in vivo, as occurs in cases of Alzheimer's disease.

PMID- 19752236
TI  - A novel role for plasmin-mediated degradation of opsonizing antibody in the
      evasion of host immunity by virulent, but not attenuated, Francisella tularensis.
AB  - Opsonization by Abs represents a critical component of the host immune response
      against many pathogens. The mechanisms by which virulent microbes evade this
      protective response are not completely understood. In disease mediated by
      Francisella tularensis, Ab can effectively protect against infections with
      attenuated strains, for example, LVS, but not virulent strains such as SchuS4.
      Thus, it is likely that SchuS4 has mechanisms, which are not present in LVS, that
      allow evasion of opsonization by Ab, dampening the protective effects of these
      host molecules. Here we demonstrate that evasion of Ab-mediated opsonization and
      phagocytosis by the highly virulent SchuS4 is associated with its ability to bind
      the host serine protease plasmin. SchuS4, but not the closely related LVS, bound
      active plasmin. Plasmin bound SchuS4 degraded exogenous and opsonizing Abs,
      whereas LVS failed to do so. Furthermore, plasmin-mediated inhibition of Ab
      opsonization by SchuS4 also inhibited Ab-mediated uptake of this bacterium by
      macrophages. Ab-mediated uptake of uncoated and opsonized SchuS4 elicited a
      strong proinflammatory response in infected macrophages. However, plasmin-coated,
      opsonized SchuS4 poorly elicited production of these protective proinflammatory
      cytokines. This unique host-pathogen interplay is a novel immune evasion strategy
      utilized by virulent F. tularensis, and it provides one explanation for the
      ability of Ab to protect against attenuated, but not virulent, strains of F.
      tularensis. This mechanism may also represent a more common hereto unrecognized
      strategy by which virulent bacteria evade detection and clearance by Ig.

PMID- 19752237
TI  - Beneficial immunomodulation by Streptococcus mutans anti-P1 monoclonal antibodies
      is Fc independent and correlates with increased exposure of a relevant target
      epitope.
AB  - We showed previously that deliberate immunization of BALB/c mice with immune
      complexes (IC) of the cariogenic bacterium Streptococcus mutans and mAbs against
      its surface adhesin P1 results in changes in the specificity and isotype of
      elicited anti-P1 Abs. Depending on the mAb, changes were beneficial, neutral, or
      detrimental, as measured by the ability of the serum from immunized mice to
      inhibit bacterial adherence to human salivary agglutinin by a BIAcore surface
      plasmon resonance assay. The current study further defined changes in the host
      response that result from immunization with IC containing beneficial mAbs, and
      evaluated mechanisms by which beneficial immunomodulation could occur in this
      system. Immunomodulatory effects varied depending upon genetic background, with
      differing results in C57BL/6 and BALB/c mice. Desirable effects following IC
      immunization were observed in the absence of activating FcRs in BALB/c Fcer1g
      transgenic mice. mAb F(ab')(2) mediated desirable changes similar to those
      observed using intact IgG. Sera from IC-immunized BALB/c mice that were better
      able to inhibit bacterial adherence demonstrated an increase in Abs able to
      compete with an adherence-inhibiting anti-P1 mAb, and binding of a beneficial
      immumomodulatory mAb to S. mutans increased exposure of that epitope. Consistent
      with a mechanism involving a mAb-mediated structural alteration of P1 on the cell
      surface, immunization with truncated P1 derivatives lacking segments that
      contribute to recognition by beneficial immunomodulatory mAbs resulted in an
      improvement in the ability of elicited serum Abs to inhibit bacterial adherence
      compared with immunization with the full-length protein.

PMID- 19752238
TI  - Suppression of ongoing T cell-mediated autoimmunity by peptide-MHC class II dimer
      vaccination.
AB  - Tissue-specific autoimmune diseases such as type 1 diabetes (T1D) are
      characterized by T cell-driven pathology. Administration of autoantigenic
      peptides provides a strategy to selectively target the pathogenic T cell
      response. Indeed, treatment with beta cell peptides effectively prevents T1D in
      NOD mice. However, the efficacy of peptide immunotherapy generally wanes as beta
      cell autoimmunity progresses and islet inflammation increases. With the goal of
      enhancing the efficacy of peptide immunotherapy, soluble (s)IA(g7)-Ig dimers
      covalently linked to beta cell autoantigen-derived peptides were tested for the
      capacity to suppress late preclinical T1D. NOD female mice with established beta
      cell autoimmunity were vaccinated i.v. with a short course of sIA(g7)-Ig dimers
      tethered to peptides derived from glutamic acid decarboxylase (GAD)65 (sIA(g7)
      pGAD65). Treatment with sIA(g7)-pGAD65 dimers and the equivalent of only
      approximately 7 microg of native peptide effectively blocked the progression of
      insulitis and the development of diabetes. Furthermore, suppression of T1D was
      dependent on beta cell-specific IL-10-secreting CD4+ T cells, although the
      frequency of GAD65-specific FoxP3-expressing CD4+ T cells was also increased in
      sIA(g7)-pGAD65 dimer vaccinated NOD mice. These results demonstrate that MHC
      class II-Ig dimer vaccination is a robust approach to suppress ongoing T cell
      mediated autoimmunity, and may provide a superior strategy of adjuvant-free
      peptide-based immunotherapy to induce immunoregulatory T cells.

PMID- 19752239
TI  - Critical role of TLR4 response in the activation of microglia induced by ethanol.
AB  - Microglial cells are the primary immune effector cells in the brain and play a
      pivotal role in the neuroinflammatory processes associated with a variety of
      neurological and pathological disorders. Alcohol consumption induces brain
      damage, although the neuropathological processes are poorly understood. We
      previously suggested that ethanol promotes inflammatory processes in the brain,
      up-regulating inflammatory mediators and signaling pathways associated with IL
      1RI/TLR4 receptors. In the present study we investigate whether ethanol induces
      microglia activation by stimulating TLR4 response and whether this response
      causes neuronal death and contributes to ethanol-induced neuroinflammatory
      damage. We demonstrate that ethanol activates microglia and stimulates NF-kappaB,
      MAPKs, and MyD88-independent (IFN regulatory factor-3, IFN-beta) pathways to
      trigger the production of inflammatory mediators, causing neuronal death. The
      inflammatory response induced by ethanol is completely abrogated in microglia of
      TLR4-deficient mice (TLR4(-/-)), thus supporting the role of these receptors in
      microglia activation and neuronal death. In accord with the in vitro findings,
      acute ethanol administration induces microglia activation (CD11b(+) cells) in
      cerebral cortex of TLR4(+/+) mice, but not in TLR4(-/-) mice. Taken together, our
      results not only provide the first evidence of the critical role of the TLR4
      response in the ethanol-induced microglia activation, but also new insight into
      the basic mechanisms participating in ethanol-induced neuroinflammatory damage.

PMID- 19752240
TI  - Targeting NF-kappa B with a natural triterpenoid alleviates skin inflammation in
      a mouse model of psoriasis.
AB  - Psoriasis vulgaris is a common chronic inflammatory skin disease involving
      cytokines and an activated cellular immune system. At variance to skin from
      patients with atopic dermatitis or from healthy subjects, human psoriatic skin
      lesions exhibit strong activation of transcription factor NF-kappaB that is
      mainly confined to dermal macrophages, whereas only a few dendritic cells but no
      CD3+ lymphocytes show activated NF-kappaB. Since NF-kappaB signaling is required
      for the induction and/or function of many cytokines and aberrant cytokine
      expression has been proposed as an underlying cause of psoriasis, we investigated
      whether NF-kappaB targeting would affect the course of the disease in the CD18
      hypomorphic (CD18(hypo)) mouse model of psoriasis. When mice with severe
      psoriasiform lesions were treated systemically or locally with the IkappaB kinase
      inhibitor acetyl-11-keto-beta-boswellic acid (AKbetaBA), NF-kappaB signaling and
      the subsequent NF-kappaB-dependent cytokine production as shown by the TNF-alpha
      production of macrophages were profoundly suppressed. Additionally, application
      of the compound counteracted the intradermal MCP-1, IL-12, and IL-23 expression
      in previously lesional skin areas, led to resolution of the abundant immune cell
      infiltrates, and significantly reduced the increased proliferation of the
      keratinocytes. Overall, the AKbetaBA treatment was accompanied by a profound
      improvement of the psoriasis disease activity score in the CD18(hypo) mice with
      reconstitution of a nearly normal phenotype within the chosen observation period.
      Our data demonstrate that NF-kappaB signaling is pivotal for the pathogenesis in
      the CD18(hypo) mouse model of psoriasis. Therefore, targeting NF-kappaB might
      provide an effective strategy for the treatment of psoriasis.

PMID- 19752241
TI  - Signaling pathways from cannabinoid receptor-1 activation to inhibition of N
      methyl-D-aspartic acid mediated calcium influx and neurotoxicity in dorsal root
      ganglion neurons.
AB  - Although the activation of cannabinoid receptor-1 (CB1) receptors by cannabinoids
      is known to inhibit neuronal hyperexcitability and reduce excitotoxic cell death,
      the mechanistic links between these two actions remain elusive. We tested the
      hypothesis that activation of CB1 receptors inhibits N-methyl-d-aspartic acid
      (NMDA)-mediated calcium influx and cell death via the inositol triphosphate
      (IP(3)) signaling pathway in both primary dorsal root ganglia neurons and a
      cultured neuronal cell line (F-11 cells). These cells were pretreated with the
      cannabinoid agonist (R)-(+)-[2,3-dihydro-5-methyl-3-(4
      morpholinylmethyl)pyrrolo[1,2,3-de)-1,4-benzoxazin-6-yl]-1-napthalenylmethanone
      (R-(+)-WIN 55,212-2; WIN) before exposure to NMDA. Concentrations of cytosolic
      calcium were measured with the ratiometric calcium indicator, Fura-2, and cell
      death was determined by a cell viability test. WIN dose-dependently attenuated
      both the calcium influx and cell death induced by NMDA. These effects were
      blocked by selective cannabinoid CB1 receptor antagonists N-(piperidin-1-yl)-5-(4
      chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide
      (SR141716A) or N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4
      methyl-1H-pyrazole-3-carboxamide (AM251), but not CB2 receptor antagonist N-[(1S)
      endo-1,3,3,-trimethylbicyclo[2.2.1]heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4
      methyl-benzyl)-pyrazole-3-carboxamide (SR144528). It is interesting to note that
      a transient Ca(2+) signal was observed after the acute application of WIN. This
      Ca(2+) increase was blocked by a CB1 receptor antagonist AM251, IP(3) receptor
      antagonist 2- aminoethyl diphenylborinate, or by depleting intracellular Ca(2+)
      stores with the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin. Removal
      of extracellular Ca(2+), on the other hand, had no effect on the CB1 receptor
      induced Ca(2+) increase. These data suggest that WIN triggers a cascade of
      events: it activates the CB1 receptor and the IP(3) signaling pathway, stimulates
      the release of Ca(2+) from intracellular stores, raises the cytosolic Ca(2+)
      levels, and inhibits the NMDA-mediated Ca(2+) influx and cell death through a
      process that remains to be determined.

PMID- 19752242
TI  - [The decentralized training program and the retention of general practitioners in
      Quebec's Lower St. Lawrence Region].
AB  - OBJECTIVE: To assess the effect of decentralized training programs, financial
      incentives, and physicians' origins on whether general practitioners continue to
      practise in an area. DESIGN: Our data were obtained from the physician database
      maintained by the Bas-Saint-Laurent Regional Department of Health and Social
      Services and from responses to a mailed questionnaire completed by physicians in
      the study. SETTING: The Lower St. Lawrence Region of Quebec. PARTICIPANTS:
      General practitioners who practised in the area between 1985 and 2003. METHOD: We
      used the Cox proportional hazards model of survival analysis to ascertain which
      variables were related to retaining physicians in the area. RESULTS: The adjusted
      probability of physicians remaining in Bas-Saint-Laurent after being exposed to
      the area through rural rotations had an odds ratio of 2.12 (P = .15). The
      probability of remaining in the area climbed to an odds ratio of 4.5 (P < .01)
      for physicians originally from the Bas-Saint-Laurent region. Financial incentives
      appeared to make little difference to whether physicians were retained in the
      area. CONCLUSION: The most promising strategies for retaining rural general
      practitioners are recruiting candidates from rural areas and exposing medical
      students to rural practice through decentralized training.

PMID- 19752243
TI  - The teaching issue.

PMID- 19752245
TI  - Helping to prepare future physicians: every family physician's responsibility?

PMID- 19752247
TI  - Give patients free blood pressure home-monitoring kits.

PMID- 19752248
TI  - Hair dryer in the bath not necessarily fatal.

PMID- 19752249
TI  - Canadian centre of expertise for electrical injury.

PMID- 19752250
TI  - Disappointing advertisement.

PMID- 19752251
TI  - PEP for bat exposure?

PMID- 19752252
TI  - Exercise and knee osteoarthritis: benefit or hazard?
AB  - OBJECTIVE: To determine whether physical exercise constitutes a benefit or a risk
      in the development and progression of knee osteoarthritis. QUALITY OF EVIDENCE:
      MEDLINE, EMBASE, DARE, ACP Journal Club, and Cochrane databases were searched
      from registry inception to January 2009 using MeSH headings or text words,
      including osteoarthritis, arthritis and knee and exercise, physical training, and
      run. Reference lists from retrieved articles, citation listings when available,
      and related articles suggested in PubMed were also evaluated. For individuals
      without osteoarthritis, strong level II evidence was found (limited by problems
      with blinding and randomization); for those with pre-existing knee
      osteoarthritis, robust level I evidence was available. MAIN MESSAGE: Knee
      osteoarthritis is a major contributor to disability in seniors, and patients have
      expressed concern that continued exercise might lead to knee symptoms in later
      years. Studies done on subjects self-selected for exercise and followed for
      substantial periods of time show no evidence of accelerated development of
      osteoarthritis, provided injury is avoided. Further, there is good evidence for
      reduced pain and disability with exercise in this cohort compared with controls.
      Patients with established osteoarthritis are shown to derive uniform benefit to
      physical functioning, with reduction of pain and disability, using aerobic,
      muscle strengthening, aquatic, or physiotherapy-based exercise modalities.
      CONCLUSION: Provided trauma is avoided, moderate exercise does not lead to
      acceleration of knee osteoarthritis, whether or not there is evidence of pre
      existing disease. In either case there appears to be improved physical
      functioning and reduction of pain and disability in those who exercise. It is
      likely that exercise interventions are underused in the management of established
      knee osteoarthritis symptoms.

PMID- 19752253
TI  - Challenges to diagnosing colorectal cancer during pregnancy.
AB  - QUESTION: My patient is 13 weeks pregnant and has experienced rectal bleeding and
      vomiting. Should I send her for a colonoscopy to rule out colorectal malignancies
      or should I wait until after delivery? ANSWER: The data on colorectal cancer in
      pregnancy are scarce; however, as the presenting features of colorectal cancer
      overlap with those of pregnancy itself, there is a risk of development of
      advanced disease, with poorer prognosis at diagnosis. Therefore, it is strongly
      recommended that this patient, who is in her second trimester, undergo at least a
      flexible sigmoidoscopy, which is presumed safe during pregnancy, with or without
      a liver ultrasound and carcinoembryonic antigen detection based on pretest
      probability according to her other risk factors.

PMID- 19752254
TI  - Magnesium for treatment of asthma in children.
AB  - QUESTION: Magnesium is considered adjuvant therapy for moderate to severe asthma
      exacerbations in adults, but can it be used to treat children? ANSWER: Magnesium
      seems to be beneficial in the treatment of moderate to severe asthma in children.
      It is a safe drug to administer, but there have been minor side effects reported,
      such as epigastric or facial warmth, flushing, pain and numbness at the infusion
      site, dry mouth, malaise, and hypotension. Owing to its bronchodilating and anti
      inflammatory effects, magnesium is an encouraging adjuvant therapy for pediatric
      patients who do not respond to conventional treatment in acute severe
      exacerbations. Future studies should focus on establishing the optimal dosage for
      maximal benefits and the best route of administration. Magnesium should also be
      considered as a prophylactic treatment.

PMID- 19752255
TI  - Management of stomatitis.

PMID- 19752256
TI  - Dermacase. Atrophoderma of Pasini and Pierini.

PMID- 19752257
TI  - Genetics: type 2 diabetes.

PMID- 19752258
TI  - Taking the stress out of individualizing ADHD drug therapy.

PMID- 19752259
TI  - Use of electronic medical records: reminders and decision aids for chronic
      disease management.

PMID- 19752260
TI  - Interprofessional education in academic family medicine teaching units: a
      functional program and culture.
AB  - PROBLEM ADDRESSED: The new family health teams (FHTs) in Ontario were designed to
      enable interprofessional collaborative practice in primary care; however, many
      health professionals have not been trained in an interprofessional environment.
      OBJECTIVE OF PROGRAM: To provide health professional learners with an
      interprofessional practice experience in primary care that models teamwork and
      collaborative practice skills. PROGRAM DESCRIPTION: The 2 academic teaching units
      of the FHT at McMaster University in Hamilton, Ont, employ 6 types of health
      professionals and provide learning environments for family medicine residents and
      students in a variety of health care professions. Learners engage in formal
      interprofessional education activities and mixed professional and learner
      clinical consultations. They are immersed in an established interprofessional
      practice environment, where all team members are valued and contribute
      collaboratively to patient care and clinic administration. Other contributors to
      the success of the program include the physical layout of the clinics, the
      electronic medical record communications system, and support from leadership for
      the additional clinical time commitment of delivering interprofessional
      education. CONCLUSION: This academic FHT has developed a program of
      interprofessional education based partly on planned activities and logistic
      enablers, and largely on immersing learners in a culture of long-standing
      interprofessional collaboration.

PMID- 19752261
TI  - Teaching-skills training programs for family medicine residents: systematic
      review of formats, content, and effects of existing programs.
AB  - OBJECTIVE: To review the literature on teaching-skills training programs for
      family medicine residents and to identify formats and content of these programs
      and their effects. DATA SOURCES: Ovid MEDLINE (1950 to mid-July 2008) and the
      Education Resources Information Center database (pre-1966 to mid-July 2008) were
      searched using and combining the MeSH terms teaching, internship and residency,
      and family practice; and teaching, graduate medical education, and family
      practice. STUDY SELECTION: The initial MEDLINE and Education Resources
      Information Center database searches identified 362 and 33 references,
      respectively. Titles and abstracts were reviewed and studies were included if
      they described the format or content of a teaching-skills program or if they were
      primary studies of the effects of a teaching-skills program for family medicine
      residents or family medicine and other specialty trainees. The bibliographies of
      those articles were reviewed for unidentified studies. A total of 8 articles were
      identified for systematic review. Selection was limited to articles published in
      English. SYNTHESIS: Teaching-skills training programs for family medicine
      residents vary from half-day curricula to a few months of training. Their content
      includes leadership skills, effective clinical teaching skills, technical
      teaching skills, as well as feedback and evaluation skills. Evaluations mainly
      assessed the programs' effects on teaching behaviour, which was generally found
      to improve following participation in the programs. Evaluations of learner
      reactions and learning outcomes also suggested that the programs have positive
      effects. CONCLUSION: Family medicine residency training programs differ from all
      other residency training programs in their shorter duration, usually 2 years, and
      the broader scope of learning within those 2 years. Few studies on teaching
      skills training, however, were designed specifically for family medicine
      residents. Further studies assessing the effects of teaching-skills training in
      family medicine residents are needed to stimulate development of adapted programs
      for the discipline. Future research should also assess how residents' teaching
      skills training can affect their learners' clinical training and eventually
      patient care.

PMID- 19752262
TI  - Resident and program director perspectives on third-year family medicine
      programs.
AB  - OBJECTIVE: To determine the views of family medicine (FM) program directors,
      third-year program coordinators, and residents on the factors affecting demand
      and allocation of postgraduate year 3 (PGY3) positions and the effects of these
      programs on the professional activities of program graduates. DESIGN: Cross
      sectional surveys and key informant interviews. SETTING: Ontario (FM residents)
      and across Canada (program directors) in 2006. PARTICIPANTS: All FM residents in
      Ontario and all core program directors and PGY3 program coordinators nationally
      were eligible to participate in the surveys. Eighteen key informant interviews
      were conducted, all in Ontario. Interviewees included all FM program directors,
      selected PGY3 program coordinators, residents, and other community stakeholders.
      METHODS: Resident surveys were Web-based; invitations to participate were
      delivered by FM programs via e-mail lists. The program director and coordinator
      surveys were postal surveys. Interviews were audiotaped and transcribed, and the
      authors coded the interviews for themes. MAIN FINDINGS: Response rates for the
      surveys were 34% to 39% for residents and 78% for program directors and
      coordinators. Respondents agreed that programs should include flexible training
      options of varied duration. Demand for training is determined more by resident
      need than community or health system factors, and is either increasing or stable.
      Overall, respondents believed that approximately one-third of core program
      graduates should have the opportunity for PGY3 training. They thought re-entry
      from practice should be permitted, but mandatory return-of-service agreements
      were not desired. Program allocation and resident selection is a complex process
      with resident merit playing an important role. Respondents expected PGY3
      graduates to practise differently than PGY2 graduates and to provide improved
      quality of care in their fields. They also thought that PGY3 graduates might play
      larger roles in leadership and teaching than core program graduates. CONCLUSION:
      It is likely that PGY3 programs will continue to grow and form an increasingly
      important part of the FM training system in Canada. Flexible programs that can
      adapt to changing educational, health system, and community needs are essential.
      Training programs and national and provincial colleges of FM will also need to
      ensure that these physicians are provided with opportunities to maintain their
      links with the rest of the FM community.

PMID- 19752263
TI  - Practice patterns of graduates of 2- and 3-year family medicine programs: in
      Ontario, 1996 to 2004.
AB  - OBJECTIVE: To compare patterns of practice between graduates of core 2-year
      family medicine (FM) training programs and those completing an additional
      postgraduate year (PGY3) of training. DESIGN: Retrospective cohort study using
      administrative data from the Ontario Health Insurance Plan. SETTING: Ontario.
      PARTICIPANTS: Graduates of Ontario FM residency programs from 1996 to 2002 who
      provided insured services in Ontario for 1 or more fiscal years between 1996 and
      2004. MAIN OUTCOME MEASURES: Proportion of physician years of service in which a
      minimum number of services were provided in each of the following categories:
      anesthesia, emergency medicine (EM), home visits, hospital visits, nursing home
      visits, intrapartum obstetrics, palliative care, office-only practice, and rural
      locations, as well as deciles for proportion of billings for emergency department
      work and "quasi-specialty" designations based on billing patterns. Results are
      stratified by type of training and years in practice. RESULTS: Graduates of PGY3
      programs are significantly more likely to practise in a range of nonoffice
      settings than their counterparts who completed core 2-year FM training programs.
      Differences were the most marked in areas in which additional training had been
      undertaken, but also extended to other categories. There was no effect on the
      proportion practising in rural locations, unless the training was undertaken in a
      rural setting or in anesthesia. Physicians including EM in their practices were
      more likely to practise mostly or almost all EM if they had undertaken either EM
      programs or self-directed programs at non-northern training sites. Very few
      graduates of any type were classified as belonging to a quasi-specialty group,
      other than those who completed care of the elderly or palliative care
      (hospitalist) and anesthesia programs. CONCLUSION: Completion of a PGY3 program
      is strongly associated with increased participation in practice outside the
      office, particularly in the area of the training provided.

PMID- 19752264
TI  - This business of caring.

PMID- 19752265
TI  - Taking time to watch: observation and learning in family practice.

PMID- 19752270
TI  - ST-246 inhibits in vivo poxvirus dissemination, virus shedding, and systemic
      disease manifestation.
AB  - Orthopoxvirus infections, such as smallpox, can lead to severe systemic disease
      and result in considerable morbidity and mortality in immunologically naive
      individuals. Treatment with ST-246, a small-molecule inhibitor of virus egress,
      has been shown to provide protection against severe disease and death induced by
      several members of the poxvirus family, including vaccinia, variola, and
      monkeypox viruses. Here, we show that ST-246 treatment not only results in the
      significant inhibition of vaccinia virus dissemination from the site of
      inoculation to distal organs, such as the spleen and liver, but also reduces the
      viral load in organs targeted by the dissemination. In mice intranasally infected
      with vaccinia virus, virus shedding from the nasal and lung mucosa was
      significantly lower (approximately 22- and 528-fold, respectively) upon ST-246
      treatment. Consequently, virus dissemination from the nasal site of replication
      to the lung also was dramatically reduced, as evidenced by a 179-fold difference
      in virus levels in nasal versus bronchoalveolar lavage. Furthermore, in ACAM2000
      immunized mice, vaccination site swabs showed that ST-246 treatment results in a
      major (approximately 3,900-fold by day 21) reduction in virus detected at the
      outside surfaces of lesions. Taken together, these data suggest that ST-246 would
      play a dual protective role if used during a smallpox bioterrorist attack. First,
      ST-246 would provide therapeutic benefit by reducing the disease burden and
      lethality in infected individuals. Second, by reducing virus shedding from those
      prophylactically immunized with a smallpox vaccine or harboring variola virus
      infection, ST-246 could reduce the risk of virus transmission to susceptible
      contacts.

PMID- 19752271
TI  - In vitro sensitivity testing of Leishmania clinical field isolates:
      preconditioning of promastigotes enhances infectivity for macrophage host cells.
AB  - Diagnostic material from patients with leishmaniasis is generally available as
      promastigotes, and proper testing for susceptibility to first-line drugs by the
      intracellular amastigote assay is frequently hampered by the poor infectivity of
      the promastigotes for the macrophage host cell. Several conditions for
      optimization of the in vitro metacyclogenesis and cell infectivity of Leishmania
      donovani, L. guyanensis, and L. braziliensis field strains obtained from patients
      receiving standard antimony medication were investigated. Triggering log-phase
      promastigotes to become amastigote-like by increasing the temperature or
      acidifying the culture medium was not successful. Adequate metacyclogenesis and
      the highest levels of macrophage infection were obtained after 5-day-old late-log
      phase promastigote cultures were preconditioned at 25 degrees C to pH 5.4 for 24
      h in Schneider's medium prior to infection. The susceptibility assay with primary
      peritoneal mouse macrophages included pentavalent antimony (Sb(V); sodium
      stibogluconate), trivalent antimony (Sb(III); potassium antimonyl tartrate),
      miltefosine, and the experimental drug PX-6518. All strains were sensitive to
      miltefosine (50% inhibitory concentration [IC(50)] < 10 microM) and PX-6518
      (IC(50) < 2 microg/ml) but showed distinct susceptibility to Sb(V) and/or
      Sb(III), depending on whether they were derived from cured, relapse, or
      nonresponder patients. Within the available set of Leishmania species and
      strains, simultaneous Sb(V)-Sb(III) resistance was clearly associated with
      treatment failure; however, a larger set of isolates is still needed to judge the
      predictive value of Sb(V)-Sb(III) susceptibility profiling on treatment outcome.
      In conclusion, the proposed conditioning protocol further contributes toward a
      more standardized laboratory model for evaluation of the drug sensitivities of
      field isolates.

PMID- 19752272
TI  - Unbound cephalothin pharmacokinetics in adult burn patients are related to the
      elapsed time after injury.
AB  - Cephalothin (cefalotin) pharmacokinetics were evaluated for nine severely burned
      patients (42% +/- 9% mean burn areas) and five healthy volunteers by using non
      plasma-protein-bound concentration-time profiles. Burn patients gave increased
      mean residence times (36%) and reduced total clearances (25%). Mean residence
      times and distribution volumes increased between 1 and 4 days posttrauma,
      suggesting that burn patient pharmacokinetics change during the initial fluid
      resuscitation phase of treatment.

PMID- 19752273
TI  - Role of Plasmodium falciparum digestive vacuole plasmepsins in the specificity
      and antimalarial mode of action of cysteine and aspartic protease inhibitors.
AB  - Hemoglobin (Hb) degradation is essential for the growth of the intraerythrocytic
      stages of malarial parasites. This process, which occurs inside an acidic
      digestive vacuole (DV), is thought to involve the action of four aspartic
      proteases, termed plasmepsins (PMs). These enzymes have received considerable
      attention as potential antimalarial drug targets. Leveraging the availability of
      a set of PM-knockout lines generated in Plasmodium falciparum, we report here
      that a wide range of previously characterized or novel aspartic protease
      inhibitors exert their antimalarial activities independently of their effect on
      the DV PMs. We also assayed compounds previously shown to inhibit cysteine
      proteases residing in the DV. The most striking observation was a ninefold
      increase in the potency of the calpain inhibitor N-acetyl-leucinyl-leucinyl
      norleucinal (ALLN) against parasites lacking all four DV PMs. Genetic ablation of
      PM III or PM IV also decreased the level of parasite resistance to the beta
      hematin binding antimalarial chloroquine. On the basis of the findings of drug
      susceptibility and isobologram assays, as well as the findings of studies of the
      inhibition of Hb degradation, morphological analyses, and stage specificity, we
      conclude that the DV PMs and falcipain cysteine proteases act cooperatively in Hb
      hydrolysis. We also identify several aspartic protease inhibitors, designed to
      target DV PMs, which appear to act on alternative targets early in the
      intraerythrocytic life cycle. These include the potent diphenylurea compound GB
      III-32, which was found to be fourfold less potent against a P. falciparum line
      overexpressing plasmepsin X than against the parental nontransformed parasite
      line. The identification of the mode of action of these inhibitors will be
      important for future antimalarial drug discovery efforts focusing on aspartic
      proteases.

PMID- 19752274
TI  - High level of cross-resistance between kanamycin, amikacin, and capreomycin among
      Mycobacterium tuberculosis isolates from Georgia and a close relation with
      mutations in the rrs gene.
AB  - The aminoglycosides kanamycin and amikacin and the macrocyclic peptide
      capreomycin are key drugs for the treatment of multidrug-resistant tuberculosis
      (MDR-TB). The increasing rates of resistance to these drugs and the possible
      cross-resistance between them are concerns for MDR-TB therapy. Mutations in the
      16S rRNA gene (rrs) have been associated with resistance to each of the drugs,
      and mutations of the tlyA gene, which encodes a putative rRNA methyltransferase,
      are thought to confer capreomycin resistance in Mycobacterium tuberculosis
      bacteria. Studies of possible cross-resistance have shown variable results. In
      this study, the MICs of these drugs for 145 clinical isolates from Georgia and
      the sequences of the rrs and tlyA genes of the isolates were determined. Of 78
      kanamycin-resistant strains, 9 (11.5%) were susceptible to amikacin and 16
      (20.5%) were susceptible to capreomycin. Four strains were resistant to
      capreomycin but were susceptible to the other drugs, whereas all amikacin
      resistant isolates were resistant to kanamycin. Sequencing revealed six types of
      mutations in the rrs gene (A514C, C517T, A1401G, C1402T, C1443G, T1521C) but no
      mutations in the tlyA gene. The A514C, C517T, C1443G, and T1521C mutations showed
      no association with resistance to any of the drugs. The A1401G and C1402T
      mutations were observed in 65 kanamycin-resistant isolates and the 4 capreomycin
      resistant isolates, respectively, whereas none of the susceptible isolates showed
      either of those mutations. The four mutants with the C1402T mutations showed high
      levels of resistance to capreomycin but no resistance to kanamycin and amikacin.
      Detection of the A1401G mutation appeared to be 100% specific for the detection
      of resistance to kanamycin and amikacin, while the sensitivities reached 85.9%
      and 94.2%, respectively.

PMID- 19752275
TI  - Complete nucleotide sequence of pCTX-M360, an intermediate plasmid between pEL60
      and pCTX-M3, from a multidrug-resistant Klebsiella pneumoniae strain isolated in
      China.
AB  - In this work we report the characterization of plasmid pCTX-M360, isolated from a
      Klebsiella pneumoniae strain from China and encoding the CTX-M-3 extended
      spectrum beta-lactamase. Sequence analysis of pCTX-M360 revealed extensive
      similarity with pEL60 and pCTX-M3, two other enterobacterial plasmids of the
      IncL/M incompatibility group. Compared to pEL60, pCTX-M360 contains several
      insertions but lacks most of a 27-kb insert found in pCTX-M3, suggesting that it
      could be an evolutionary intermediate between pEL60 and pCTX-M3.

PMID- 19752276
TI  - In vivo activity of a novel anti-methicillin-resistant Staphylococcus aureus
      cephalosporin, ceftaroline, against vancomycin-susceptible and -resistant
      Enterococcus faecalis strains in a rabbit endocarditis model: a comparative study
      with linezolid and vancomycin.
AB  - We assessed the in vitro and in vivo efficacy of the novel parenteral broad
      spectrum cephalosporin ceftaroline against Enterococcus faecalis in time-kill
      experiments and in a rabbit endocarditis model with simulated human dosing.
      Ceftaroline was more active than either vancomycin or linezolid against
      vancomycin-sensitive and -resistant isolates of E. faecalis.

PMID- 19752278
TI  - Mutational upregulation of a resistance-nodulation-cell division-type multidrug
      efflux pump, SdeAB, upon exposure to a biocide, cetylpyridinium chloride, and
      antibiotic resistance in Serratia marcescens.
AB  - Serratia marcescens is an important opportunistic pathogen in hospitals, where
      quaternary ammonium compounds are often used for disinfection. The aim of this
      study is to elucidate the effect of a biocide on the emergence of biocide- and
      antibiotic-resistant mutants and to characterize the molecular mechanism of
      biocide resistance in Serratia marcescens. A quaternary ammonium compound
      resistant strain, CRes01, was selected by exposing a wild-type strain of S.
      marcescens to cetylpyridinium chloride. The CRes01 cells exhibited 2- to 16-fold
      more resistance than the wild-type cells to biocides and antibiotics, including
      cetylpyridinium chloride, benzalkonium chloride, chlorhexidine gluconate,
      fluoroquinolones, tetracycline, and chloramphenicol, and showed increased
      susceptibilities to beta-lactam antibiotics and N-dodecylpyridinium iodide.
      Mutant cells accumulated lower levels of norfloxacin than the parent cells in an
      energized state but not in a de-energized state, suggesting that the strain
      produced a multidrug efflux pump(s). To verify this assumption, we knocked out a
      putative efflux pump gene, sdeAB, in CRes01 and found that the knockout restored
      susceptibility to most quaternary ammonium compounds and antibiotics, to which
      the CRes01 strain showed resistance. On the basis of these and other results, we
      concluded that S. marcescens gains resistance to both biocides and antibiotics by
      expressing the SdeAB efflux pump upon exposure to cetylpyridinium chloride.

PMID- 19752277
TI  - Novel ribosomal mutations in Staphylococcus aureus strains identified through
      selection with the oxazolidinones linezolid and torezolid (TR-700).
AB  - TR-700 (torezolid), the active moiety of the novel oxazolidinone phosphate
      prodrug TR-701, is highly potent against gram-positive pathogens, including
      strains resistant to linezolid (LZD). Here we investigated the potential of
      Staphylococcus aureus strains ATCC 29213 (methicillin-susceptible S. aureus
      [MSSA]) and ATCC 33591 (methicillin-resistant S. aureus [MRSA]) to develop
      resistance to TR-700. The spontaneous frequencies of mutation of MSSA 29213 and
      MRSA 33591 resulting in reduced susceptibility to TR-700 at 2 x the MIC were 1.1
      x 10(-10) and 1.9 x 10(-10), respectively. These values are approximately 16-fold
      lower than the corresponding LZD spontaneous mutation frequencies of both
      strains. Following 30 serial passages in the presence of TR-700, the MIC for MSSA
      29213 remained constant (0.5 microg/ml) while increasing eightfold (0.25 to 2.0
      microg/ml) for MRSA 33591. Serial passage of MSSA 29213 and MRSA 33591 in LZD
      resulted in 64- and 32-fold increases in LZD resistance (2 to 128 microg/ml and 1
      to 32 microg/ml, respectively). Domain V 23S rRNA gene mutations (Escherichia
      coli numbering) found in TR-700-selected mutants included T2500A and a novel
      coupled T2571C/G2576T mutation, while LZD-selected mutants included G2447T,
      T2500A, and G2576T. We also identified mutations correlating with decreased
      susceptibility to TR-700 and LZD in the rplC and rplD genes, encoding the 50S
      ribosomal proteins L3 and L4, respectively. L3 mutations included Gly152Asp,
      Gly155Arg, Gly155Arg/Met169Leu, and DeltaPhe127-His146. The only L4 mutation
      detected was Lys68Gln. TR-700 maintained a fourfold or greater potency advantage
      over LZD against all strains with ribosomal mutations. These data bring to light
      a variety of novel and less-characterized mutations associated with S. aureus
      resistance to oxazolidinones and demonstrate the low resistance potential of
      torezolid.

PMID- 19752279
TI  - Phase I evaluation of the safety and pharmacokinetics of a single-dose
      intravenous injection of a murine monoclonal antibody against Hantaan virus in
      healthy volunteers.
AB  - Anti-Hantaan virus monoclonal antibody (AHM) is a murine monoclonal antibody
      against Hantaan virus being developed for the treatment of hemorrhagic fever with
      renal syndrome. The purpose of the present study was to describe the tolerance
      and pharmacokinetics of an intravenously administered single ascending dose of
      AHM in Chinese healthy volunteers. Four cohorts of 22 healthy subjects received
      AHM at 2.5 to 20 mg, and the results indicated that AHM was well tolerated. We
      established a highly sensitive, rapid, and accurate immunoassay for the kinetic
      analysis of AHM in serum. Serial blood samples were obtained after intravenous
      administration for up to 17 days. A one-compartment model was determined to best
      describe the disposition of AHM. The maximal level in serum and the area under
      the serum concentration-time curve were proportional to the doses. The mean
      clearance, the half-life, and the volume of distribution were constant,
      irrespective of the dose. AHM was slowly cleared and had a half-life of
      approximately 110 h. These data support the use of a treatment regimen in which
      AHM is given only once intravenously.

PMID- 19752280
TI  - Alterations in two-component regulatory systems of phoPQ and pmrAB are associated
      with polymyxin B resistance in clinical isolates of Pseudomonas aeruginosa.
AB  - Polymyxins are often the only option to treat acquired multidrug-resistant
      Pseudomonas aeruginosa. Polymyxin susceptibility in P. aeruginosa PAO1 is
      associated with the lipopolysaccharide structure that is determined by arnBCADTEF
      and modulated by phoPQ and pmrAB. We examined five clonally unrelated clinical
      isolates of polymyxin B-resistant P. aeruginosa to investigate the molecular
      basis of polymyxin resistance. All isolates grew with 4 microg/ml polymyxin B
      (MIC, 8 microg/ml), whereas P. aeruginosa PAO1 grew with 0.25 mug/ml polymyxin B
      (MIC, 0.5 microg/ml). The resistant isolates were converted to susceptible ones
      (the MICs fell from 8 to 0.5 microg/ml) following the introduction of phoPQ (four
      isolates) and pmrAB (one isolate), which had been cloned from strain PAO1. DNA
      sequence analysis revealed that a single-nucleotide substitution in three
      isolates replaced a single amino acid of PhoQ, the deletion of 17 nucleotides in
      one isolate truncated the protein of PhoQ, and two nucleotide substitutions in
      one isolate replaced two amino acids of PmrB. The involvement of these amino acid
      substitutions or the truncated protein of PhoQ and PmrB in polymyxin B resistance
      was confirmed using strain PAO1 lacking phoPQ or pmrAB that was transformed by
      phoPQ or pmrAB containing the amino acid substitutions or the truncated protein.
      The resistant clinical isolates were sensitized by the inactivation of arnBCADTEF
      (the MICs fell from 8 to 0.5 microg/ml). These results suggest that polymyxin B
      resistance among clinical isolates of P. aeruginosa is associated with
      alterations in two-component regulatory systems of phoPQ or pmrAB.

PMID- 19752281
TI  - Methicillin-resistant Staphylococcus aureus screening by online immunometric
      monitoring of bacterial growth under selective pressure.
AB  - Rapid, high-throughput screening tools are needed to contain the spread of
      hospital-acquired methicillin (meticillin)-resistant Staphylococcus aureus (MRSA)
      strains. Most techniques used in current clinical practice still require time
      consuming culture for primary isolation of the microbe. We present a new
      phenotypic assay for MRSA screening. The technique employs a two-photon excited
      fluorescence (TPX) detection technology with S. aureus-specific antibodies that
      allows the online monitoring of bacterial growth in a single separation-free
      process. Different progressions of fluorescence signals are recorded for
      methicillin-susceptible and -resistant strains when the growth of S. aureus is
      monitored in the presence of cefoxitin. The performance of the new technique was
      evaluated with 20 MRSA strains, 6 methicillin-susceptible S. aureus strains, and
      7 coagulase-negative staphylococcal strains and two different monoclonal S.
      aureus-specific antibodies. When either of these antibodies was used, the
      sensitivity and the specificity of the TPX assay were 100%. All strains were
      correctly classified within 8 to 12 h, and up to 70 samples were simultaneously
      analyzed on a single 96-well microtiter plate. As a phenotypic method, the TPX
      assay is suited for screening purposes. The final definition of methicillin
      resistance in any S. aureus strain should be based on the presence of the mecA
      gene. The main benefit afforded by the initial use of the TPX methodology lies in
      its low cost and applicability to high-throughput analysis.

PMID- 19752282
TI  - Nonclonal emergence of colistin-resistant Klebsiella pneumoniae isolates from
      blood samples in South Korea.
AB  - In vitro activities of colistin and other drugs were tested against 221
      Klebsiella pneumoniae isolates that were collected between 2006 and 2007 in nine
      tertiary care South Korean hospitals from patients with bacteremia. The clonality
      of colistin-resistant K. pneumoniae (CRKP) isolates was assessed by multilocus
      sequence typing (MLST). We found that 15 isolates (6.8%) were resistant to
      colistin. MLST showed that CRKP isolates were nonclonal, with colistin resistance
      in K. pneumoniae occurring independently and not by clonal spreading.

PMID- 19752283
TI  - Tn6060, a transposon from a genomic island in a Pseudomonas aeruginosa clinical
      isolate that includes two class 1 integrons.
AB  - A 25,441-bp transposon was recovered from a Pseudomonas aeruginosa clinical
      isolate. While the transposition module was >99% identical to sequence of Tn1403,
      the element had been subject to rearrangements, with two In70.2-like class 1
      integrons inserted into it in an unusual "tail-to-tail" configuration. One
      cassette array was the same as that in In70.2; however, the second was different,
      generating a transposon that collectively includes six resistance cassettes.

PMID- 19752284
TI  - Therapeutic drug monitoring of posaconazole: a monocentric study with 54 adults.
AB  - Posaconazole is a potent broad-spectrum triazole antifungal. Little is known
      about the prevalence and risk factors for low plasma posaconazole concentrations
      (PPCs). We retrospectively reviewed all adult patients whose PPCs were measured
      after at least 5 days of treatment between April 2006 and July 2008 at the
      Hopital Necker Enfants Malades. A low PPC was defined as a concentration lower
      than 500 ng/ml. Fifty-four patients were included: 36 receiving prophylactic (200
      mg three times a day) and 18 receiving curative (400 mg twice a day) posaconazole
      therapy. The prevalence of low PPCs was 44% (16/36) in the prophylaxis group and
      22% (4/18) in the curative-treatment group. In the prophylaxis group, low PPCs
      tended to be more frequent in cases of digestive disease (62.5% versus 30%; P =
      0.051) and were significantly more frequent among patients with diarrhea (71.4%
      versus 27%; P = 0.009) or mucositis (100% versus 33%; P = 0.004). In the curative
      treatment group, low PPCs were significantly more frequent in cases of diarrhea
      (75% versus 7%; P = 0.018). In the prophylaxis group, the only two patients who
      subsequently developed invasive fungal infections exhibited low PPCs. The only
      adverse event was hepatotoxicity for 2/54 patients (3.7%), which was not related
      to high plasma drug concentrations. In conclusion, low PPC is common,
      significantly more frequent in cases of diarrhea or mucositis, and potentially
      associated with subsequent invasive fungal infection. Therapeutic drug monitoring
      of posaconazole is therefore mandatory for immunosuppressed adults, at least for
      those with gastrointestinal disorders.

PMID- 19752285
TI  - Two-parameter characterization of chromosome-scale recombination rate.
AB  - The genome-wide recombination rate (RR) of a species is often described by one
      parameter, the ratio between total genetic map length (G) and physical map length
      (P), measured in centimorgans per megabase (cM/Mb). The value of this parameter
      varies greatly between species, but the cause for these differences is not
      entirely clear. A constraining factor of overall RR in a species, which may cause
      increased RR for smaller chromosomes, is the requirement of at least one chiasma
      per chromosome (or chromosome arm) per meiosis. In the present study, we quantify
      the relative excess of recombination events on smaller chromosomes by a linear
      regression model, which relates the genetic length of chromosomes to their
      physical length. We find for several species that the two-parameter regression, G
      = G(0) + k x P , provides a better characterization of the relationship between
      genetic and physical map length than the one-parameter regression that runs
      through the origin. A nonzero intercept (G(0)) indicates a relative excess of
      recombination on smaller chromosomes in a genome. Given G(0), the parameter k
      predicts the increase of genetic map length over the increase of physical map
      length. The observed values of G(0) have a similar magnitude for diverse species,
      whereas k varies by two orders of magnitude. The implications of this strategy
      for the genetic maps of human, mouse, rat, chicken, honeybee, worm, and yeast are
      discussed.

PMID- 19752287
TI  - Autoimmune targets of heart and skeletal muscles in myasthenia gravis.
AB  - OBJECTIVE: To investigate the clinical, histological, and immunological features
      of patients with myasthenia gravis (MG) who also developed myocarditis and/or
      myositis. DESIGN: Observational and retrospective case series. SETTING: Keio
      University, Hanamaki General Hospital, Kanazawa University, Nagasaki University,
      and Juntendo University. PATIENTS: A cohort of 8 patients with MG with clinically
      defined inflammatory myopathies. INTERVENTIONS: Clinical and histological
      features were described. Serological analyses included MG-related antistriational
      autoantibodies (those to titin, ryanodine receptor, muscular voltage-gated
      potassium channel Kv1.4) and myositis-specific autoantibodies. RESULTS: Of 924
      patients with MG, 8 (0.9%) had inflammatory myopathies. The mean (SD) onset age
      of MG was 55.3 (10.3) years. All patients showed severe symptoms with bulbar
      involvement; 5 patients had myasthenic crisis and 4 had invasive thymoma.
      Myocarditis was found in 3 patients and myositis in 6. Myocarditis, developing 13
      to 211 months after the MG onset, was characterized by heart failure and
      arrhythmias. Myositis, developing before or at the same time as MG, affected limb
      and paraspinal muscles. Histological findings of skeletal muscles showed CD8(+)
      lymphocyte infiltration. Seven patients had 1 of these antistriational
      autoantibodies but not myositis-specific autoantibodies. Immunomodulatory therapy
      was required for all patients and was effective for both MG and inflammatory
      myopathies, although 1 patient died. CONCLUSIONS: Heart and skeletal muscles are
      autoimmune targets in some patients with MG. This autoimmunity has a broad
      clinical spectrum with antistriational autoantibodies.

PMID- 19752289
TI  - Flawed measurement of brachial tonometry for calculating aortic pressure?

PMID- 19752290
TI  - The choice of thiazide diuretics: why chlorthalidone may replace
      hydrochlorothiazide.

PMID- 19752291
TI  - Newly reported hypertension after military combat deployment: research
      implications from a biopsychosocial perspective.

PMID- 19752292
TI  - Caveolin-1 and dopamine-mediated internalization of NaKATPase in human renal
      proximal tubule cells.
AB  - In moderate sodium-replete states, dopamine 1-like receptors (D1R/D5R) are
      responsible for regulating >50% of renal sodium excretion. This is partly
      mediated by internalization and inactivation of NaKATPase, when associated with
      adapter protein 2. We used dopaminergic stimulation via fenoldopam (D1-like
      receptor agonist) to study the interaction among D1-like receptors, caveolin-1
      (CAV1), and the G protein-coupled receptor kinase type 4 in cultured human renal
      proximal tubule cells (RPTCs). We compared 2 groups of RPTCs, 1 of cell lines
      that were isolated from normal subjects (nRPTCs) and a second group of cell lines
      that have D1-like receptors that are uncoupled (uncoupled RPTCs) from adenylyl
      cyclase second messengers. In nRPTCs, fenoldopam increased the plasma membrane
      expression of D1R (10.0-fold) and CAV1 (1.3-fold) and markedly decreased G
      protein-coupled receptor kinase type 4 by 94+/-8%; no effects were seen in
      uncoupled RPTCs. Fenoldopam also increased the association of adapter protein 2
      and NaKATPase by 53+/-9% in nRPTCs but not in uncoupled RPTCs. When CAV1
      expression was reduced by 86.0+/-8.5% using small interfering RNA, restimulation
      of the D1-like receptors with fenoldopam in nRPTCs resulted in only a 7+/-9%
      increase in association between adapter protein 2 and NaKATPase. Basal CAV1
      expression and association with G protein-coupled receptor kinase type 4 was
      decreased in uncoupled RPTCs (58+/-5% decrease in association) relative to
      nRPTCs. We conclude that the scaffolding protein CAV1 is necessary for the
      association of D1-like receptors with G protein-coupled receptor kinase type 4
      and the adapter protein 2-associated reduction in plasma membrane NaKATPase.

PMID- 19752293
TI  - Newly reported hypertension after military combat deployment in a large
      population-based study.
AB  - High-stress situations, such as combat deployments, are a potential risk factor
      for hypertension. Although stress is postulated to increase blood pressure, the
      underlying role of stress on hypertension is not well established. We sought to
      determine the relations between combat deployment-induced stress and
      hypertension. The Millennium Cohort baseline questionnaire (2001-2003) was
      completed by 77,047 US active-duty and Reserve/National Guard members. Follow-up
      was completed by 55,021 responders approximately 3 years later (2004-2006).
      Multivariable logistic regression was used to estimate the 3-year risk of newly
      reported hypertension, adjusting for general and mental health, demographics, and
      occupational and behavioral characteristics. After applying exclusion criteria,
      our analyses included 36 061 service members. Subanalyses of deployers included
      8829 participants. Newly reported hypertension was identified in 6.9% of the
      cohort between baseline and follow-up, many of whom had deployed on military
      operations in support of the conflicts in Iraq and Afghanistan. After adjusting,
      deployers who experienced no combat exposures were less likely to report
      hypertension than nondeployers (odds ratio: 0.77; 95% CI: 0.67 to 0.89). Among
      deployers, those reporting multiple combat exposures were 1.33 times more likely
      to report hypertension compared with noncombat deployers (95% CI: 1.07 to 1.65).
      Although military deployers, in general, had a lower incidence of hypertension
      than nondeployers, deployment with multiple stressful combat exposures appeared
      to be a unique risk factor for newly reported hypertension.

PMID- 19752294
TI  - Translating what is known about neurological complications of coronary artery
      bypass graft surgery into action.

PMID- 19752295
TI  - Emerging viral infections of the central nervous system: part 2.
AB  - The first part of this review ended with a discussion of new niches for known
      viruses as illustrated by viral central nervous system (CNS) disease associated
      with organ transplant and the syndrome of human herpesvirus 6-associated
      posttransplant acute limbic encephalitis. In this part, we begin with a
      continuation of this theme, reviewing the association of JC virus-associated
      progressive multifocal leukoencephalopathy (PML) with novel immunomodulatory
      agents. This part then continues with emerging viral infections associated with
      importation of infected animals (monkeypox virus), then spread of vectors and
      enhanced vector competence (chikungunya virus [CHIK]), and novel viruses causing
      CNS infections including Nipah and Hendra viruses and bat lyssaviruses (BLV).

PMID- 19752296
TI  - Preventive antibiotics for infections in acute stroke: a systematic review and
      meta-analysis.
AB  - OBJECTIVE: To provide a systematic overview and meta-analysis of randomized
      clinical trials evaluating preventive antibiotics in patients with acute stroke.
      DATA SOURCES: The MEDLINE (1966-February 2009) and Cochrane databases and
      reference lists of retrieved articles. STUDY SELECTION: Randomized controlled
      trials on preventive antibiotic treatment in stroke. For inclusion, at least case
      fatality or infection rate had to be recorded. DATA EXTRACTION: Each study was
      scored for methodological key issues and appraised by the Jadad scale. We
      extracted the data using a predetermined protocol and included all patients who
      were randomized or who started therapy in an intent-to-treat analysis. DATA
      SYNTHESIS: We identified 4 randomized clinical trials including 426 patients; 94%
      had ischemic stroke. Study interventions were fluoroquinolones in 2 and
      tetracycline or a combination of beta-lactam antibiotic with beta-lactamase
      inhibitor in 1. Therapy was started within 24 hours of stroke onset. Duration of
      therapy varied between 3 and 5 days. The methodological quality ranged from 2 to
      5 on the Jadad scale, and studies were subject to potential bias. The proportion
      of patients with infection was significantly smaller in the antibiotic group than
      in the placebo/control group (32 of 136 [23.5%] vs 53 of 139 [38.1%] patients).
      The pooled odds ratio for infection was 0.44 (95% confidence interval, 0.23
      0.86). Ten of 210 patients (4.8%) in the antibiotic group died, compared with 13
      of 216 (6.0%) in the placebo/control group. The pooled odds ratio for mortality
      was 0.63 (95% confidence interval, 0.22-1.78). No major harm or toxicity was
      reported. CONCLUSIONS: In adults with acute stroke, preventive antibiotics
      reduced the risk of infection, but did not reduce mortality. The observed effect
      warrants evaluation of preventive antibiotics in large stroke trials.

PMID- 19752297
TI  - Robotic devices as therapeutic and diagnostic tools for stroke recovery.
AB  - The understanding that recovery of brain function after stroke is imperfect has
      prompted decades of effort to engender speedier and better recovery through
      environmental manipulation. Clinical evidence has shown that the performance
      plateau exhibited by patients with chronic stroke, usually signaling an end of
      standard rehabilitation, might represent a period of consolidation rather than a
      performance optimum. These results highlight the difficulty of translating
      pertinent neurological data into pragmatic changes in clinical programs. This
      opinion piece focuses on upper limb impairment reduction after robotic training.
      We propose that robotic devices be considered as novel tools that might be used
      alone or in combination with novel pharmacology and other bioengineered devices.
      Additionally, robotic devices can measure motor performance objectively and will
      contribute to a detailed phenotype of stroke recovery.

PMID- 19752298
TI  - Strokes after cardiac surgery and relationship to carotid stenosis.
AB  - OBJECTIVE: To critically examine the role of significant carotid stenosis in the
      pathogenesis of postoperative stroke following cardiac operations. DESIGN:
      Retrospective cohort study. SETTING: Single tertiary care hospital. PARTICIPANTS:
      A total of 4335 patients undergoing coronary artery bypass grafting, aortic valve
      replacement, or both. MAIN OUTCOME MEASURES: Incidence, subtype, and arterial
      distribution of stroke. RESULTS: Clinically definite stroke was detected in 1.8%
      of patients undergoing cardiac operations during the same admission. Only 5.3% of
      these strokes were of the large-vessel type, and most strokes (76.3%) occurred
      without significant carotid stenosis. In 60.0% of cases, strokes identified via
      computed tomographic head scans were not confined to a single carotid artery
      territory. According to clinical data, in 94.7% of patients, stroke occurred
      without direct correlation to significant carotid stenosis. Undergoing combined
      carotid and cardiac operations increases the risk of postoperative stroke
      compared with patients with a similar degree of carotid stenosis but who
      underwent cardiac surgery alone (15.1% vs 0%; P = .004). CONCLUSIONS: There is no
      direct causal relationship between significant carotid stenosis and postoperative
      stroke in patients undergoing cardiac operations. Combining carotid and cardiac
      procedures is neither necessary nor effective in reducing postoperative stroke in
      patients with asymptomatic carotid stenosis.

PMID- 19752299
TI  - Occupation and risk of parkinsonism: a multicenter case-control study.
AB  - BACKGROUND: We examined risk of parkinsonism in occupations (agriculture,
      education, health care, welding, and mining) and toxicant exposures (solvents and
      pesticides) putatively associated with parkinsonism. OBJECTIVE: To investigate
      occupations, specific job tasks, or exposures and risk of parkinsonism and
      clinical subtypes. DESIGN: Case-control. SETTING: Eight movement disorders
      centers in North America. PARTICIPANTS: Inclusion criteria were parkinsonism
      (>or=2 cardinal signs), diagnosis within 8 years of recruitment (to minimize
      survival bias), and ability to participate in detailed telephone interviews.
      Control subjects were primarily nonblood relatives or acquaintances of patients.
      MAIN OUTCOME MEASURES: This multicenter case-control study compared lifelong
      occupational and job task histories to determine associations with parkinsonism
      and certain clinical subtypes (postural instability and gait difficulty and age
      at diagnosis <or=50 years). RESULTS: Findings in 519 cases and 511 controls were
      analyzed. Work in agriculture, education, health care, or welding was not
      associated with increased risk of parkinsonism. Unexpected increased risks
      associated with legal, construction and extraction, or religious occupations were
      not maintained after adjustment for duration. Risk of parkinsonism increased with
      pesticide use (odds ratio, 1.90; 95% confidence interval, 1.12-3.21), use of any
      of 8 pesticides mechanistically associated with experimental parkinsonism (2.20;
      1.02-4.75), and use of 2,4-dichlorophenoxyacetic acid (2.59; 1.03-6.48). None of
      the specific occupations, job tasks, or task-related exposures were associated
      with younger age at diagnosis (<or=50 years). Ever working in business and
      finance, legal occupations, construction and extraction, or transportation and
      material moving was associated with postural instability and gait difficulty
      subtype of parkinsonism. Tobacco use was inversely associated with parkinsonism
      risk. CONCLUSION: The association of disease risk with pesticides support a
      toxicant-induced cause of parkinsonism.

PMID- 19752300
TI  - Comparison of risk factor profiles in incidental Lewy body disease and Parkinson
      disease.
AB  - OBJECTIVE: To explore whether associations of potential risk factors for
      incidental Lewy body disease (iLBD) are similar to those for Parkinson disease
      (PD). DESIGN: Brain autopsy study (1988-2004) of subjects without evidence of
      neurodegenerative disease or tremor who were evaluated by at least 1 physician
      within 1 year of death. Researchers analyzed incidental Lewy pathology blinded to
      clinical abstraction. SETTING: Olmsted County, Minnesota. Subjects Residents of
      Olmsted County and the immediate vicinity aged older than 60 years. MAIN OUTCOME
      MEASURES: Whether risk factors previously associated with PD in Olmsted County
      are also associated with iLBD. RESULTS: Of 235 subjects, 34 had iLBD (14.5%). The
      overall risk factor profiles for iLBD and PD were fairly similar between the 2
      sets of odds ratio (OR) estimates, with 11 of 16 ORs in the same direction. Prior
      Olmsted County studies documented 7 risk factors with statistically significant
      associations with PD; for physician occupation and caffeine intake, the ORs for
      iLBD were in the same direction and statistically significant, whereas for
      education, head injury, and number of children, they were in the same direction
      but not significant; they were in the opposite direction but not statistically
      significant for depression and anxiety. Incidental Lewy body disease was not
      associated with various end-of-life conditions or causes of death, though these
      patients were slightly older and more likely cachectic. CONCLUSIONS: Based on
      this exploratory study, iLBD and PD appear to have similar risk factor profiles.
      Thus, at least some cases of iLBD could represent preclinical PD, arrested PD, or
      a partial syndrome due to a lesser burden of causative factors. Incidental Lewy
      body disease is not explained by nonspecific end-of-life brain insults.

PMID- 19752301
TI  - Extrapyramidal signs before and after diagnosis of incident Alzheimer disease in
      a prospective population study.
AB  - BACKGROUND: Extrapyramidal signs (EPSs) are commonly accepted as a feature of
      Alzheimer disease (AD) and may influence both the profile of impairment and
      prognosis. OBJECTIVE: To examine rates of occurrence and risk factors for all
      types of EPSs and to describe the impact of EPSs over time on the clinical course
      of AD. DESIGN: Longitudinal study. SETTING: The Washington Heights Hamilton
      Heights Inwood Columbia Aging Project. Patients A total of 388 patients with
      incident AD (mean age, 79 years; 71.4% female). MAIN OUTCOME MEASURES:
      Extrapyramidal signs rated by means of a standardized portion of the Unified
      Parkinson's Disease Rating Scale; prevalence and incidence rates and cumulative
      risk for non-drug-induced EPSs; and rates of change in EPSs over time, taking
      into account potential covariates. RESULTS: Extrapyramidal signs were detected in
      12.3% of patients at first evaluation and 22.6% at last evaluation. In a
      multivariate-adjusted generalized estimating equation model of change, total EPS
      score increased at an annual rate of 1.3%. Women (relative risk [RR], 1.57; P =
      .03), older patients (RR, 1.03; P = .02), and those with EPSs at baseline (RR,
      2.07; P = .001) had greater rates of cognitive decline. CONCLUSIONS:
      Extrapyramidal signs occur frequently and progress significantly in AD. Patients
      with incident AD and concomitant EPSs have a greater rate of cognitive decline
      than do patients with incident AD but without EPSs.

PMID- 19752302
TI  - Treatment of neuromyelitis optica with mycophenolate mofetil: retrospective
      analysis of 24 patients.
AB  - BACKGROUND: Neuromyelitis optica (NMO) is the first inflammatory autoimmune
      demyelinating disease of the central nervous system for which a specific
      antigenic target has been identified; the marker autoantibody NMO-IgG
      specifically recognizes the astrocytic water channel aquaporin 4. Current
      evidence strongly suggests that NMO-IgG may be pathogenic. Since disability
      accrues incrementally related to attacks, attack prevention with
      immunosuppressive therapy is the mainstay of preventing disability. OBJECTIVE: To
      evaluate the efficacy and safety of mycophenolate mofetil therapy in NMO spectrum
      disorders. DESIGN: Retrospective case series with prospective telephone follow
      up. SETTING: Mayo Clinic Health System. Patients Twenty-four patients with NMO
      spectrum disorders (7 treatment-naive). Intervention Mycophenolate mofetil
      (median dose of 2000 mg per day). MAIN OUTCOME MEASURES: Annualized relapse rates
      and disability (Expanded Disability Status Scale). RESULTS: At a median follow-up
      of 28 months (range, 18-89 months), 19 patients (79%) were continuing treatment.
      The median duration of treatment was 27 months (range, 1-89 months). The median
      annualized posttreatment relapse rate was lower than the pretreatment rate (0.09;
      range, 0-1.5; and 1.3; range, 0.23-11.8, respectively; P < .001). Disability
      stabilized or decreased in 22 of 24 patients (91%). One patient died of disease
      complications during follow-up. Six patients (25%) noted adverse effects during
      treatment with mycophenolate. CONCLUSION: Mycophenolate is associated with
      reduction in relapse frequency and stable or reduced disability in patients with
      NMO spectrum disorders.

PMID- 19752303
TI  - Diagnosis of neuromyelitis spectrum disorders: comparative sensitivities and
      specificities of immunohistochemical and immunoprecipitation assays.
AB  - OBJECTIVE: To compare the sensitivity and specificity of immunofluorescence (IF)
      and immunoprecipitation (IP) assays using green fluorescent protein-tagged
      aquaporin-4 (AQP4) in 6335 patients for whom serological evaluation was requested
      on a service basis. DESIGN: Case-control study. SETTING: Mayo Clinic
      Neuroimmunology Laboratory (Rochester, Minnesota) and Departments of Neurology
      (Rochester, Minnesota; Scottsdale, Arizona; and Jacksonville, Florida). Patients
      Group 1, 835 Mayo Clinic patients, 100 with a neuromyelitis optica (NMO) spectrum
      disorder diagnosis and 735 without NMO spectrum disorder; group 2, 5500 non-Mayo
      Clinic patients. Main Outcome Measure Sensitivity and specificity of each assay
      for NMO or NMO spectrum disorder, individually and combined. RESULTS: In group 1,
      the sensitivity rates for NMO were IF, 58%; IP, 33%; and combined assays, 63%.
      The sensitivity rates for relapsing longitudinally extensive transverse myelitis
      were IF, 29%; IP, 6%; and combined assays, 29%. The specificity rates for NMO and
      relapsing longitudinally extensive transverse myelitis were IF, 99.6%; IP, 99.3%;
      and combined assays, 99.2%. In group 2, NMO-IgG was detected by IF in 498 of 5500
      patients (9.1%) and by IP in 331 patients (6.0%); 76 of the 331 patients
      seropositive by IP (23%) were negative by IF. Clinical information was available
      for 124 patients (including 16 of those seropositive by IP only); 123 had a
      definite NMO spectrum disorder and 1 was at risk for NMO (monophasic optic
      neuritis). CONCLUSIONS: In this large, clinical practice-based study, NMO-IgG
      detected by IF or IP was highly specific for NMO spectrum disorders. The IP assay
      was significantly less sensitive than IF. Combined testing improved sensitivity
      by 5%.

PMID- 19752304
TI  - Multiple sclerosis with predominant, severe cognitive impairment.
AB  - OBJECTIVE: To describe the characteristics of multiple sclerosis (MS) presenting
      with severe cognitive impairment as its primary disabling manifestation. DESIGN:
      Retrospective case series. SETTING: Tertiary referral center. Patients Patients
      were identified through the Mayo Clinic data retrieval system (1996-2008) with
      definite MS (McDonald criteria) and severe cognitive impairment as their primary
      neurological symptom without accompanying significant MS-related impairment or
      alternative diagnosis for cognitive dysfunction. Twenty-three patients meeting
      inclusion criteria were compared regarding demographics, clinical course, and
      radiological features. MAIN OUTCOME MEASURES: Demographic, clinical, and
      radiological characteristics of the disease. RESULTS: Twelve patients were men.
      The median age of the first clinical symptom suggestive of central nervous system
      demyelination was 33 years, and severe MS-related cognitive impairment developed
      at a median age of 39 years. Cognitive impairment could be dichotomized as
      subacute fulminant (n = 9) or chronic progressive (n = 14) in presentation, which
      corresponded to subsequent relapsing or progressive MS courses. Study patients
      commonly exhibited psychiatric (65%), mild cerebellar (57%), and cortical
      symptoms and signs (eg, seizure, aphasia, apraxia) (39%). Fourteen of 21 (67%),
      where documented, smoked cigarettes. Brain magnetic resonance imaging
      demonstrated diffuse cerebral atrophy in 16 and gadolinium-enhancing lesions in
      11. Asymptomatic spinal cord magnetic resonance imaging lesions were present in
      12 of 16 patients (75%). Immunomodulatory therapies were generally ineffective in
      improving these patients. CONCLUSIONS: We describe patients with MS whose
      clinical phenotype is characterized by severe cognitive dysfunction and prominent
      cortical and psychiatric signs presenting as a subacute fulminant or chronic
      progressive clinical course. Cigarette smokers may be overrepresented in this
      phenotype.

PMID- 19752305
TI  - Cortical lesions and atrophy associated with cognitive impairment in relapsing
      remitting multiple sclerosis.
AB  - BACKGROUND: Neuropsychological deficits in patients with multiple sclerosis (MS)
      have been shown to be associated with the major pathological substrates of the
      disease, ie, inflammatory demyelination and neurodegeneration. Double inversion
      recovery sequences allow cortical lesions (CLs) to be detected in the brain of
      patients with MS. Modern postprocessing techniques allow cortical atrophy to be
      assessed reliably. OBJECTIVE: To investigate the contribution of cortical gray
      matter lesions and tissue loss to cognitive impairment in patients with relapsing
      remitting MS. DESIGN: Cross-sectional survey. SETTING: Referral, hospital-based
      MS clinic. Patients Seventy patients with relapsing-remitting MS. MAIN OUTCOME
      MEASURES: Neuropsychological performance was tested using the Rao Brief
      Repeatable Battery of Neuropsychological Tests, version A. Patients who scored 2
      SDs below the mean normative values on at least 1 test of the Rao Brief
      Repeatable Battery of Neuropsychological Tests, version A, were considered to be
      cognitively impaired. A composite cognitive score (the cognitive impairment
      index) was computed. T2 hyperintense white matter lesion volume, contrast
      enhancing lesion number, CL number and volume, normalized brain volume, and
      normalized neocortical gray matter volume were also assessed. RESULTS: Twenty
      four patients with relapsing-remitting MS (34.3%) were classified as cognitively
      impaired. T2 hyperintense white matter lesion volume and contrast-enhancing
      lesion number were not different between cognitively impaired and cognitively
      unimpaired patients. Cognitively impaired patients had a higher CL number (P =
      .01) and volume (P < .001) and decreased normalized brain volume (P = .02) and
      normalized neocortical gray matter volume (P = .002) when compared with
      cognitively unimpaired patients. Multivariate analysis revealed that age (beta =
      0.228; P = .02), CL volume (beta = 0.452; P < .001), and normalized neocortical
      gray matter volume (beta = 0.349; P < .001) were independent predictors of the
      cognitive impairment index (r(2) = 0.55; F = 23.903; P < .001). CONCLUSION: The
      burden of CLs and tissue loss are among the major structural changes associated
      with cognitive impairment in relapsing-remitting MS.

PMID- 19752306
TI  - Progression of mild cognitive impairment to dementia in clinic- vs community
      based cohorts.
AB  - BACKGROUND: Mild cognitive impairment is increasingly recognized as an important
      public health problem associated with increased risk of developing dementia.
      Annual conversion rates, however, vary across different studies with clinic
      samples showing higher rates of conversion than community-based samples.
      OBJECTIVES: To establish whether the rates of conversion from mild cognitive
      impairment to dementia differed according to recruitment source and, if so, to
      investigate factors that might explain this discrepancy. DESIGN: Rates and
      predictors of conversion were examined in a prospective longitudinal study at a
      single center. SETTING: Among the participants, 46% were recruited from a
      clinical setting and 54% were recruited directly through community outreach.
      PARTICIPANTS: One hundred eleven individuals with mild cognitive impairment were
      followed up longitudinally for an average of 2.4 years (range, 0.5-4.0 years).
      MAIN OUTCOME MEASURES: Conversion from mild cognitive impairment to dementia.
      RESULTS: During the follow-up period, 28 individuals progressed to dementia with
      a mean (SD) time to conversion of 2.19 (0.72) years. The clinic sample had an
      annual conversion rate of 13%, whereas the community sample had an annual
      conversion rate of 3%. In a Cox proportional hazards model, clinic recruitment
      source alone was associated with an increased hazard of incident dementia (hazard
      ratio = 3.50; 95% confidence interval, 1.31-9.18; P = .01). When other variables
      were added to the model, only baseline functional impairment as measured by the
      Clinical Dementia Rating Scale (and no demographic, cognitive, or neuroimaging
      variables or mild cognitive impairment subtype) accounted for the differences in
      conversion rates across the 2 cohorts. CONCLUSIONS: These findings add to the
      growing literature to suggest that the degree of functional impairment at
      baseline is an important predictor of conversion to dementia and may help explain
      differences in findings between epidemiological and clinic-based studies.

PMID- 19752307
TI  - Disparate diseases due to copycat copy number variations.

PMID- 19752308
TI  - Nineteen episodes of recurrent myelitis in a woman with neuromyelitis optica and
      systemic lupus erythematosus.
AB  - OBJECTIVES: To describe the case of a patient with systemic lupus erythematosus
      (SLE) and neuromyelitis optica (NMO) who experienced 19 recurrent attacks of
      myelitis. DESIGN: Case report. SETTING: An outpatient neurorheumatology clinic at
      the Johns Hopkins Hospital devoted to care of patients with neurological
      manifestation of rheumatic diseases. Patient A woman with NMO and SLE.
      Intervention Rituximab therapy. MAIN OUTCOME MEASURES: Clinical and neuroimaging
      features of relapsing disease. RESULTS: Recurrent and increasingly severe
      myelitis attacks still occurred after treatment with rituximab. CONCLUSIONS: It
      may be progressively more difficult to prevent relapses and commensurate
      disability in patients with later stages of relapsing NMO. Recognition of NMO as
      a distinct diagnostic entity in patients with SLE and other rheumatic diseases is
      crucial, in that institution of earlier targeted immunosuppressant treatment may
      be more effective than later targeted immunosuppression. The cellular arm of the
      immune system may be recruited by pathogenic B cells and may explain why relapses
      may occur after treatment with B cell-depleting therapy.

PMID- 19752309
TI  - Prediction of neuromyelitis optica attack severity by quantitation of complement
      mediated injury to aquaporin-4-expressing cells.
AB  - BACKGROUND: Recent reports support a pathogenic role in neuromyelitis optica
      (NMO) for the aquaporin-4 (AQP4)-specific autoantibody (NMO-IgG). Neuromyelitis
      optica is an inflammatory demyelinating central nervous system disease, usually
      relapsing, that causes variable degrees of attack-related disability. The NMO-IgG
      binds in vitro to the extracellular domain of AQP4, activates complement, and
      causes astrocyte lesioning. OBJECTIVE: To compare the prognostic utility of NMO
      IgG titer and quantitative measures of complement-mediated injury to AQP4
      expressing cells in NMO attacks. DESIGN, SETTING, AND PARTICIPANTS: A
      retrospective clinical-serological correlative study at Mayo Clinic's
      Neuroimmunology Laboratory was undertaken. Over an 18-month period, we identified
      NMO-IgG-seropositive patients in whom sufficient serum and adequate clinical
      information pertaining to NMO attacks (6 severe, 6 mild) were available to
      analyze clinical-serological correlations. Sera from 9 patients with multiple
      sclerosis and 9 healthy subjects (all NMO-IgG seronegative) served as controls.
      Complement activation was measured by quantifying the number of green fluorescent
      protein-AQP4-transfected HEK 293 cells permeable to the viability dye propidium
      iodide after exposure to patient serum and active complement. MAIN OUTCOME
      MEASURES: Attack severity (mild or severe), percentage of AQP4-transfected cells
      lesioned, and NMO-IgG titer. RESULTS: The median percentage of AQP4-transfected
      cells lesioned by complement in the presence of serum from patients with NMO was
      14% for patients with mild attacks and 54% for patients with severe attacks (P =
      .005). Median complement activation values for sera from healthy subjects and
      patients with multiple sclerosis were 8% and 12%, respectively. Patients with
      mild NMO attacks and patients with severe NMO attacks did not differ
      significantly with respect to NMO-IgG titer (P = .089). CONCLUSIONS: A laboratory
      measure of complement-mediated cell injury may serve as a prognostic biomarker in
      NMO. Larger prospective studies are required to validate this observation.

PMID- 19752310
TI  - Repeated embolic stroke from an infected aortic arch graft with transesophageal
      echocardiography-documented mobile vegetation.

PMID- 19752311
TI  - Cerebral fat embolism: susceptibility-weighted magnetic resonance imaging.

PMID- 19752312
TI  - Air embolism with pneumocephalus.

PMID- 19752313
TI  - Multifocal stroke from tumor emboli.

PMID- 19752314
TI  - Thrombolysis in acute ischemic stroke with vitreous hemorrhage.

PMID- 19752315
TI  - Would you save this patient's eye or his brain?

PMID- 19752316
TI  - In vivo confocal microscopy of corneal stromal nerves in patients with peripheral
      neuropathy.

PMID- 19752317
TI  - Reducing stroke rates in patients with atrial fibrillation: how low can we go?

PMID- 19752318
TI  - Unmet potential for cardiovascular disease prevention in the United States.

PMID- 19752319
TI  - Analysis of stroke in ATHENA: a placebo-controlled, double-blind, parallel-arm
      trial to assess the efficacy of dronedarone 400 mg BID for the prevention of
      cardiovascular hospitalization or death from any cause in patients with atrial
      fibrillation/atrial flutter.
AB  - BACKGROUND: Many patients with atrial fibrillation are at high risk for stroke
      and require antithrombotic therapy. Antiarrhythmic drugs have not previously been
      shown to reduce the risk of stroke in atrial fibrillation. The effect of
      dronedarone, a new multichannel-blocking antiarrhythmic drug, on stroke has been
      evaluated in a randomized, double-blind clinical trial, ATHENA (A placebo
      controlled, double-blind, parallel-arm Trial to assess the efficacy of
      dronedarone 400 mg BID for the prevention of cardiovascular Hospitalization or
      death from any cause in patiENts with Atrial fibrillation/atrial flutter).
      METHODS AND RESULTS: Patients with persistent or paroxysmal atrial fibrillation
      and at least 1 risk factor for cardiovascular hospitalization were randomized to
      receive dronedarone (400 mg BID) or double-blind matching placebo and followed up
      for a minimum of 1 year to a common termination at 30 months. All strokes that
      occurred during the study were included in the present post hoc analysis. There
      were 4628 patients randomized to placebo or dronedarone. The baseline risk
      factors for stroke were well balanced between the 2 groups, and the baseline mean
      CHADS(2) score was 2. The baseline use of either oral anticoagulant therapy or
      antiplatelet agent alone was 60%. Dronedarone reduced the risk of stroke from
      1.8% per year to 1.2% per year (hazard ratio 0.66, 95% confidence interval 0.46
      to 0.96, P=0.027). The effect of dronedarone was similar whether or not patients
      were receiving oral anticoagulant therapy, and there was a significantly greater
      effect of dronedarone in patients with higher CHADS(2) scores. CONCLUSIONS: In
      this post hoc analysis, a reduction in stroke was observed in patients with
      atrial fibrillation who were receiving usual care, which included antithrombotic
      therapy and heart rate control, who were randomized to dronedarone. Further
      studies to investigate the effect of dronedarone and other antiarrhythmic agents
      on stroke are indicated.

PMID- 19752321
TI  - Pulmonary hypertensive medical therapy in chronic thromboembolic pulmonary
      hypertension before pulmonary thromboendarterectomy.
AB  - BACKGROUND: The currently recommended treatment for chronic thromboembolic
      pulmonary hypertension is pulmonary thromboendarterectomy (PTE). No convincing
      evidence for the use of pulmonary hypertensive medical therapy (PHT) exists in
      operable candidates. We sought to determine the prevalence of the use of PHT on
      referral for PTE and the effects on pre-PTE hemodynamics and post-PTE
      outcomes/hemodynamics. METHODS AND RESULTS: We performed a retrospective analysis
      of chronic thromboembolic pulmonary hypertension patients referred for PTE during
      2005-2007. The prevalence of PHT was determined for all patients referred to our
      institution. Hemodynamic and outcomes analysis involved only those undergoing
      PTE. Data included baseline demographics, PHT medication(s), dosage, duration of
      therapy, and time to referral. Hemodynamic data were acquired from the time of
      diagnosis, the time of referral visit, and after PTE. Outcomes included intensive
      care unit, hospital, and ventilator days; bleeding and infection rates; incidence
      of reperfusion lung injury; and in-hospital mortality. The control group (n=244)
      was compared with the PHT group (n=111); subgroups included monotherapy with
      bosentan, sildenafil, or epoprostenol and combination therapy. The prevalence of
      PHT significantly increased from 19.9% in 2005 to 37% in 2007. There was minimal
      benefit of treatment with PHT on pre-PTE mean pulmonary artery pressure, but its
      use was associated with a significant delay in time to referral for PTE. Both
      groups experienced significant improvements in hemodynamic parameters after PTE.
      The 2 groups did not differ significantly in any post-PTE outcome. Similar
      results were obtained for each subgroup. CONCLUSIONS: Our results suggest that
      PHT use has minimal effect on pre-PTE hemodynamics and no effect on post-PTE
      outcomes/hemodynamics.

PMID- 19752320
TI  - Mac-1 (CD11b/CD18) links inflammation and thrombosis after glomerular injury.
AB  - BACKGROUND: Inflammation and thrombosis coexist in several disorders. Although it
      is recognized that leukocytes may induce a procoagulant state at sites of
      inflammation, the critical molecular determinants of this process remain largely
      unknown. METHODS AND RESULTS: To examine mechanisms of inflammation-induced
      thrombosis, we developed a murine model of thrombotic glomerulonephritis (TGN), a
      known cause of acute renal failure in patients. This model, induced by
      lipopolysaccharide and antibody to the glomerular basement membrane, led to rapid
      glomerular neutrophil recruitment, thrombotic glomerular lesions with endothelial
      cell injury, and renal dysfunction. In mice immunodepleted of neutrophils or
      lacking the leukocyte-specific integrin Mac-1, neutrophil recruitment,
      endothelial injury, glomerular thrombosis, and acute renal failure were markedly
      attenuated despite the robust generation of renal cytokines. Neutrophil elastase
      is a likely effector of Mac-1 because its activity was reduced in Mac-1-deficient
      mice and the phenotype in mice deficient in Mac-1 or neutrophil elastase was
      similar. Platelets accumulated in glomerular capillaries within 4 hours of TGN
      before evidence of thrombosis. Platelet immunodepletion before TGN markedly
      exacerbated hematuria (hemorrhage), inflammation, and injury, whereas
      thrombocytopenic Mac-1-deficient mice remained resistant to disease, indicating
      that initial glomerular platelet deposition protects the vessel wall from
      neutrophil-mediated sequelae. The subsequent thrombosis relied on the interaction
      of Mac-1 on recruited neutrophils with glycoprotein Ibalpha on platelets as
      antibody-mediated disruption of this interaction attenuated TGN without affecting
      renal neutrophil accumulation. CONCLUSIONS: These observations establish Mac-1 on
      neutrophils as a critical molecular link between inflammation and thrombosis and
      suggest it as an attractive target for antithrombotic therapy.

PMID- 19752322
TI  - Regulation of vascular contractility and blood pressure by the E2F2 transcription
      factor.
AB  - BACKGROUND: Recent studies have identified a polymorphism in the endothelin
      converting enzyme (ECE)-1b promoter (-338C/A) that is strongly associated with
      hypertension in women. The polymorphism is located in a consensus binding
      sequence for the E2F family of transcription factors. E2F proteins are crucially
      involved in cell-cycle regulation, but their roles in cardiovascular function are
      poorly understood. Here, we investigated the potential role of E2F2 in blood
      pressure regulation. METHODS AND RESULTS: Tail-cuff measurements of systolic and
      diastolic blood pressures were significantly higher in E2F2-null (E2F2(-/-)) mice
      than in their wild-type littermates, and in ex vivo ring assays, aortas from the
      E2F2(-/-) mice exhibited significantly greater contractility in response to big
      endothelin-1. Big endothelin-1 is activated by ECE-1, and mRNA levels of ECE-1b,
      the repressive ECE-1 isoform, were significantly lower in E2F2(-/-) mice than in
      wild-type mice. In endothelial cells, chromatin immunoprecipitation assays
      confirmed that E2F2 binds the ECE-1b promoter, and promoter-reporter assays
      indicated that E2F2 activates ECE-1b transcription. Furthermore, loss or
      downregulation of E2F2 led to a decline in ECE-1b levels, to higher levels of the
      membranous ECE-1 isoforms (ie, ECE-1a, -1c, and -1d), and to deregulated ECE-1
      activity. Finally, Sam68 coimmunoprecipitated with E2F2, occupied the ECE-1b
      promoter (chromatin immunoprecipitation), and repressed E2F2-mediated ECE-1b
      promoter activity (promoter-reporter assays). CONCLUSIONS: Our results identify a
      cell-cycle-independent mechanism by which E2F2 regulates endothelial function,
      arterial contractility, and blood pressure.

PMID- 19752323
TI  - Association of leukocyte telomere length with echocardiographic left ventricular
      mass: the Framingham heart study.
AB  - BACKGROUND: Leukocyte telomere length (LTL) decreases over the adult life course
      owing to the cumulative burden of oxidative stress, inflammation, and exposure to
      vascular risk factors. Left ventricular (LV) mass is a biomarker of long-standing
      exposure to cardiovascular disease risk factors. We hypothesized that LTL is
      related inversely to LV mass. METHODS AND RESULTS: We related LTL (measured by
      Southern blot analysis) to echocardiographic LV mass and its components (LV
      diastolic dimension and LV wall thickness) in 850 Framingham Heart Study
      participants (mean age 58 years, 58% women) using multivariable linear regression
      with adjustment for age, sex, height, weight, systolic blood pressure,
      hypertension treatment, and smoking. Overall, multivariable-adjusted LTL was
      positively related to LV mass (beta-coefficient per SD increase 0.072; P=0.001),
      LV wall thickness (beta=0.053; P=0.01), and LV diastolic dimension (beta=0.035;
      P=0.09). We observed effect modification by hypertension status (P for
      interaction=0.02 for LV mass); LTL was more strongly associated with LV mass and
      LV wall thickness in individuals with hypertension (beta-coefficient per SD
      increment of 0.10 and 0.08, respectively; P<0.01 for both). Participants with
      hypertension who were in the top quartile of LV mass had LTL that was 250 base
      pairs longer than those in the lowest quartile (P for trend across
      quartiles=0.009). CONCLUSIONS: In contrast to our expectation, in the present
      community-based sample, LTL was positively associated with LV mass and wall
      thickness, especially so in participants with hypertension. These data are
      consistent with the hypothesis that longer LTL may be a marker of propensity to
      LV hypertrophy.

PMID- 19752325
TI  - Dehydroepiandrosterone reverses systemic vascular remodeling through the
      inhibition of the Akt/GSK3-{beta}/NFAT axis.
AB  - BACKGROUND: The remodeled vessel wall in many vascular diseases such as
      restenosis after injury is characterized by proliferative and apoptosis-resistant
      vascular smooth muscle cells. There is evidence that proproliferative and
      antiapoptotic states are characterized by a metabolic (glycolytic phenotype and
      hyperpolarized mitochondria) and electric (downregulation and inhibition of
      plasmalemmal K(+) channels) remodeling that involves activation of the Akt
      pathway. Dehydroepiandrosterone (DHEA) is a naturally occurring and clinically
      used steroid known to inhibit the Akt axis in cancer. We hypothesized that DHEA
      will prevent and reverse the remodeling that follows vascular injury. METHODS AND
      RESULTS: We used cultured human carotid vascular smooth muscle cell and saphenous
      vein grafts in tissue culture, stimulated by platelet-derived growth factor to
      induce proliferation in vitro and the rat carotid injury model in vivo. DHEA
      decreased proliferation and increased vascular smooth muscle cell apoptosis in
      vitro and in vivo, reducing vascular remodeling while sparing healthy tissues
      after oral intake. Using pharmacological (agonists and antagonists of Akt and its
      downstream target glycogen-synthase-kinase-3beta [GSK-3beta]) and molecular
      (forced expression of constitutively active Akt1) approaches, we showed that the
      effects of DHEA were mediated by inhibition of Akt and subsequent activation of
      GSK-3beta, leading to mitochondrial depolarization, increased reactive oxygen
      species, activation of redox-sensitive plasmalemmal voltage-gated K(+) channels,
      and decreased [Ca(2+)](i). These functional changes were accompanied by sustained
      molecular effects toward the same direction; by decreasing [Ca(2+)](i) and
      inhibiting GSK-3beta, DHEA inhibited the nuclear factor of activated T cells
      transcription factor, thus increasing expression of Kv channels (Kv1.5) and
      contributing to sustained mitochondrial depolarization. These results were
      independent of any steroid-related effects because they were not altered by
      androgen and estrogen inhibitors but involved a membrane G protein-coupled
      receptor. CONCLUSIONS: We suggest that the orally available DHEA might be an
      attractive candidate for the treatment of systemic vascular remodeling, including
      restenosis, and we propose a novel mechanism of action for this important hormone
      and drug.

PMID- 19752324
TI  - Chest compression fraction determines survival in patients with out-of-hospital
      ventricular fibrillation.
AB  - BACKGROUND: Quality cardiopulmonary resuscitation contributes to cardiac arrest
      survival. The proportion of time in which chest compressions are performed in
      each minute of cardiopulmonary resuscitation is an important modifiable aspect of
      quality cardiopulmonary resuscitation. We sought to estimate the effect of an
      increasing proportion of time spent performing chest compressions during cardiac
      arrest on survival to hospital discharge in patients with out-of-hospital
      ventricular fibrillation or pulseless ventricular tachycardia. METHODS AND
      RESULTS: This is a prospective observational cohort study of adult patients from
      the Resuscitation Outcomes Consortium Cardiac Arrest Epistry with confirmed
      ventricular fibrillation or ventricular tachycardia, no defibrillation before
      emergency medical services arrival, electronically recorded cardiopulmonary
      resuscitation before the first shock, and a confirmed outcome. Patients were
      followed up to discharge from the hospital or death. Of the 506 cases, the mean
      age was 64 years, 80% were male, 71% were witnessed by a bystander, 51% received
      bystander cardiopulmonary resuscitation, 34% occurred in a public location, and
      23% survived. After adjustment for age, gender, location, bystander
      cardiopulmonary resuscitation, bystander witness status, and response time, the
      odds ratios of surviving to hospital discharge in the 2 highest categories of
      chest compression fraction compared with the reference category were 3.01 (95%
      confidence interval 1.37 to 6.58) and 2.33 (95% confidence interval 0.96 to
      5.63). The estimated adjusted linear effect on odds ratio of survival for a 10%
      change in chest compression fraction was 1.11 (95% confidence interval 1.01 to
      1.21). CONCLUSIONS: An increased chest compression fraction is independently
      predictive of better survival in patients who experience a prehospital
      ventricular fibrillation/tachycardia cardiac arrest.

PMID- 19752326
TI  - Perioperative risk predictors of cardiac outcomes in patients undergoing liver
      transplantation surgery.
AB  - BACKGROUND: Cardiac risk assessment for perioperative outcomes of liver
      transplantation patients is limited. We examined the outcomes of an older
      intermediate-cardiac-risk group of patients undergoing liver transplantation
      surgery. METHODS AND RESULTS: Patients who had liver transplantation surgery
      between 2001 and 2005 were studied. The 3 outcomes analyzed were nonfatal
      myocardial infarction, death, and either outcome within the first 30 days after
      the liver transplantation surgery. Of 403 patients (mean age, 52+/-9 years; 67%
      male), 106 (26%) were diabetic, 84 (21%) were hypertensive, and 173 (43%) had a
      history of smoking. There were 48 total events (12%), 25 myocardial infarctions
      (7%), and 38 deaths (9%) recorded during the perioperative period. From the final
      multivariate model, history of coronary artery disease, prior stroke, and
      postoperative sepsis predicted greater risk (P=0.014; odds ratio [OR], 4.0; 95%
      confidence interval [CI], 1.3 to 11.8; P=0.025; OR, 6.6; 95% CI, 1.3 to 33.8; and
      P<0.001; OR, 7.5; 95% CI, 3.3 to 17.1, respectively). Use of perioperative beta
      blockers was protective (P=0.004; OR, 0.20; 95% CI, 0.1 to 0.6) for combined
      cardiac outcomes. For the outcome of death on multivariate analysis,
      postoperative sepsis and increased interventricular septal thickness predicted
      risk (P<0.001; OR, 8.6; 95% CI, 3.5 to 20.9; and P=0.027; OR, 2.8; 95% CI, 1.1 to
      7.2, respectively), whereas the use of perioperative beta-blockers was again
      protective (P=0.012; OR, 0.07; 95% CI, 0.01 to 0.56). CONCLUSIONS: In our study
      of cardiac risk assessment for liver transplantation surgery, history of stroke,
      coronary artery disease, postoperative sepsis, and increased interventricular
      septal thickness were markers of adverse perioperative cardiac outcomes, whereas
      use of perioperative beta-blockers was significantly protective.

PMID- 19752327
TI  - Systemic cardiac amyloidoses: disease profiles and clinical courses of the 3 main
      types.
AB  - BACKGROUND: Most studies of amyloidotic cardiomyopathy consider as a single
      entity the 3 main systemic cardiac amyloidoses: acquired monoclonal
      immunoglobulin light-chain (AL); hereditary, mutated transthyretin-related
      (ATTRm); and wild-type transthyretin-related (ATTRwt). In this study, we compared
      the diagnostic/clinical profiles of these 3 types of systemic cardiac
      amyloidosis. METHODS AND RESULTS: We conducted a longitudinal study of 233
      patients with clear-cut diagnosis by type of cardiac amyloidosis (AL, n=157;
      ATTRm, n=61; ATTRwt, n=15) at 2 large Italian centers providing coordinated
      amyloidosis diagnosis/management facilities since 1990. Average age at diagnosis
      was higher in AL than in ATTRm patients; all ATTRwt patients except 1 were
      elderly men. At diagnosis, mean left ventricular wall thickness was higher in
      ATTRwt than in ATTRm and AL. Left ventricular ejection fraction was moderately
      depressed in ATTRwt but not in AL or ATTRm. ATTRm patients less often displayed
      low QRS voltage (25% versus 60% in AL; P<0.0001) or low voltage-to-mass ratio
      (1.1+/-0.5 versus 0.9+/-0.5; P<0.0001). AL patients appeared to have greater
      hemodynamic impairment. On multivariate analysis, ATTRm was a strongly favorable
      predictor of survival, and ATTRwt predicted freedom from major cardiac events.
      CONCLUSIONS: AL, ATTRm, and ATTRwt should be considered 3 different cardiac
      diseases, probably characterized by different pathophysiological substrates and
      courses. Awareness of the diversity underlying the cardiac amyloidosis label is
      important on several levels, ranging from disease classification to diagnosis and
      clinical management.

PMID- 19752328
TI  - Trends in the prevalence of low risk factor burden for cardiovascular disease
      among United States adults.
AB  - BACKGROUND: Cohorts consistently show that individuals with low levels of
      cardiovascular risk factors experience low rates of subsequent cardiovascular
      events. Our objective was to examine the prevalence and trends in low risk factor
      burden for cardiovascular disease among adults in the US population. METHODS AND
      RESULTS: We used data from adults 25 to 74 years of age who participated in 4
      national surveys. We created an index of low risk from the following variables:
      not currently smoking, total cholesterol <5.17 mmol/L (<200 mg/dL) and not using
      cholesterol-lowering medications, systolic blood pressure <120 mm Hg and
      diastolic blood pressure <80 mm Hg and not using antihypertensive medications,
      body mass index <25 kg/m(2), and not having been previously diagnosed with
      diabetes mellitus. The age-adjusted prevalence of low risk factor burden
      increased from 4.4% during 1971 to 1975 to 10.5% during 1988 to 1994 before
      decreasing to 7.5% during 1999 to 2004 (P for nonlinear trend <0.001). The
      patterns were similar for men and women, although the prevalence among women
      exceeded that among men in each survey (P<0.001 for each survey). In addition,
      whites had a significantly higher prevalence of low risk factor burden than
      blacks during each survey except during 1976 to 1980 (1971 to 1975, 1988 to 1994,
      1999 to 2004: P<0.001; 1976 to 1980: P=0.154). Furthermore, a larger percentage
      of whites had a low risk factor burden than Mexican Americans during 1988 to 1994
      (P<0.001) and 1999 to 2004 (P=0.001). CONCLUSIONS: The prevalence of low risk
      factor burden for cardiovascular disease is low. The progress that had been made
      during the 1970s and 1980s reversed in recent decades.

PMID- 19752330
TI  - Combined hormone therapy at menopause and breast cancer: a warning--short-term
      use increases risk.

PMID- 19752329
TI  - Gene transfer of inducible nitric oxide synthase affords cardioprotection by
      upregulating heme oxygenase-1 via a nuclear factor-{kappa}B-dependent pathway.
AB  - BACKGROUND: Although inducible nitric oxide synthase (iNOS) is known to impart
      powerful protection against myocardial infarction, the mechanism for this
      salubrious action remains unclear. METHODS AND RESULTS: Adenovirus-mediated iNOS
      gene transfer in mice resulted 48 to 72 hours later in increased expression not
      only of iNOS protein but also of heme oxygenase (HO)-1 mRNA and protein; HO-2
      protein expression did not change. iNOS gene transfer markedly reduced infarct
      size in wild-type mice, but this effect was completely abrogated in HO-1(-/-)
      mice. At 48 hours after iNOS gene transfer, nuclear factor-kappaB was markedly
      activated. In transgenic mice with cardiomyocyte-restricted expression of a
      dominant negative mutant of IkappaBalpha (IkappaBalpha(S32A,S36A)), both basal HO
      1 levels and upregulation of HO-1 by iNOS gene transfer were suppressed.
      Chromatin immunoprecipitation analysis of mouse hearts provided direct evidence
      that nuclear factor-kappaB subunits p50 and p65 were recruited to the HO-1 gene
      promoter (-468 to -459 bp) 48 hours after iNOS gene transfer. CONCLUSIONS: This
      study demonstrates for the first time the existence of a close functional
      coupling between cardiac iNOS and cardiac HO-1: iNOS upregulates HO-1 by
      augmenting nuclear factor-kappaB binding to the region of the HO-1 gene promoter
      from -468 to -459 bp, and HO-1 then mediates the cardioprotective effects of
      iNOS. These results also reveal an important role of nuclear factor-kappaB in
      both basal and iNOS-induced expression of cardiac HO-1. Collectively, the present
      findings significantly expand our understanding of the regulation of cardiac HO-1
      and of the mechanism whereby iNOS exerts its cardioprotective actions.

PMID- 19752331
TI  - Prevention of thrombosis in ambulatory patients with cancer.
AB  - Cancer patients with solid tumors or hematologic malignancies receive most of
      their cancer treatment as outpatients. Thromboembolism, when it occurs,
      complicates the clinical care of these patients because of the associated
      morbidity and the need for anticoagulant treatment. It would seem that prevention
      of venous thromboembolism in these patients would be worthwhile. However, to date
      there are relatively few trials of anticoagulant prophylaxis in ambulatory
      patients with cancer and it is not possible to recommend prophylaxis for most
      patients. Research is needed to better define a population at high enough risk to
      warrant pharmacologic prophylaxis and to develop new antithrombotic agents for
      this indication.

PMID- 19752332
TI  - Aromatase inhibitor-associated arthralgias.

PMID- 19752333
TI  - Cost effectiveness and screening interval of lipid screening in Hodgkin's
      lymphoma survivors.
AB  - PURPOSE: Survivors of Hodgkin's lymphoma (HL) who received mediastinal
      irradiation have an increased risk of coronary heart disease. We evaluated the
      cost effectiveness of lipid screening in survivors of HL and compared different
      screening intervals. METHODS: We developed a decision-analytic model to evaluate
      lipid screening in a hypothetical cohort of 30-year-old survivors of HL who
      survived 5 years after mediastinal irradiation. We compared the following
      strategies: no screening, and screening at 1-, 3-, 5-, or 7-year intervals.
      Screen-positive patients were treated with statins. Markov models were used to
      calculate life expectancy, quality-adjusted life expectancy, and lifetime costs.
      Baseline probabilities, transition probabilities, and utilities were derived from
      published studies and US population data. Costs were estimated from Medicare fee
      schedules and the medical literature. Sensitivity analyses were performed.
      RESULTS: Using an incremental cost-effectiveness ratio (ICER) threshold of
      $100,000 per quality-adjusted life-year (QALY) saved, lipid screening at every
      interval was cost effective relative to a strategy of no screening. When
      comparing screening intervals, a 3-year interval was cost effective relative to a
      5-year interval, but annual screening, relative to screening every 3 years, had
      an ICER of more than $100,000/QALY saved. Factors with the most influence on the
      results included risk of cardiac events/death after HL, efficacy of statins in
      reducing cardiac events/death, and costs of statins. CONCLUSION: Lipid screening
      in survivors of HL, with statin therapy for screen-positive patients, improves
      survival and is cost effective. A screening interval of 3 years seems reasonable
      in the long-term follow-up of survivors of HL.

PMID- 19752334
TI  - Venous thromboembolism in the hematologic malignancies.
AB  - Patients with hematologic malignancies are at high risk of thrombotic or
      hemorrhagic complications. The incidence of these events is greatly variable and
      is influenced by many factors, including the type of disease, the type of
      chemotherapy, and the use of a central venous device. As in solid tumors, a
      number of clinical risk factors have been identified and contribute to the
      increasing thrombotic rate in hematologic malignancies. Biologic properties of
      the tumor cells can influence the hypercoagulable state of patients with these
      malignancies by several mechanisms. Of interest, oncogenes responsible for
      neoplastic transformation in leukemia also may be involved in clotting
      activation. Epidemiologic data allow an estimate of the incidence of venous
      thromboembolism (VTE) in acute leukemia, lymphomas, and multiple myeloma (MM). In
      this review, we focus on the epidemiology, pathogenesis, and VTE management in
      these three hematologic malignancies. No recommendation for routine
      thromboprophylaxis in these conditions, with the exception of MM, is available.
      Large, prospective, randomized clinical trials are needed to establish the best
      practice for thromboprophylaxis and treatment of VTE in these types of cancers.

PMID- 19752335
TI  - Real-time quantitative polymerase chain reaction detection of minimal residual
      disease by standardized WT1 assay to enhance risk stratification in acute myeloid
      leukemia: a European LeukemiaNet study.
AB  - PURPOSE: Risk stratification in acute myeloid leukemia (AML) is currently based
      on pretreatment characteristics. It remains to be established whether relapse
      risk can be better predicted through assessment of minimal residual disease
      (MRD). One proposed marker is the Wilms tumor gene WT1, which is overexpressed in
      most patients with AML, thus providing a putative target for immunotherapy,
      although in the absence of a standardized assay, its utility for MRD monitoring
      remains controversial. PATIENTS AND METHODS: Nine published and in-house real
      time quantitative polymerase chain reaction WT1 assays were systematically
      evaluated within the European LeukemiaNet; the best-performing assay was applied
      to diagnostic AML samples (n = 620), follow-up samples from 129 patients treated
      with intensive combination chemotherapy, and 204 normal peripheral blood (PB) and
      bone marrow (BM) controls. RESULTS: Considering relative levels of expression
      detected in normal PB and BM, WT1 was sufficiently overexpressed to discriminate
      > or = 2-log reduction in transcripts in 46% and 13% of AML patients, according
      to the respective follow-up sample source. In this informative group, greater WT1
      transcript reduction after induction predicted reduced relapse risk (hazard
      ratio, 0.54 per log reduction; 95% CI, 0.36 to 0.83; P = .004) that remained
      significant when adjusted for age, WBC count, and cytogenetics. Failure to reduce
      WT1 transcripts below the threshold limits defined in normal controls by the end
      of consolidation also predicted increased relapse risk (P = .004). CONCLUSION:
      Application of a standardized WT1 assay provides independent prognostic
      information in AML, lending support to incorporation of early assessment of MRD
      to develop more robust risk scores, to enhance risk stratification, and to
      identify patients who may benefit from allogeneic transplantation.

PMID- 19752336
TI  - Phase I active immunotherapy with combination of two chimeric, human epidermal
      growth factor receptor 2, B-cell epitopes fused to a promiscuous T-cell epitope
      in patients with metastatic and/or recurrent solid tumors.
AB  - PURPOSE To evaluate the maximum-tolerated dose (MTD), safety profile, and
      immunogenicity of two chimeric, B-cell epitopes derived from the human epidermal
      growth factor receptor (HER2) extracellular domain in a combination vaccine with
      a promiscuous T-cell epitope (ie, MVF) and nor-muramyl-dipeptide as adjuvant
      emulsified in SEPPIC ISA 720. PATIENTS AND METHODS Eligible patients with
      metastatic and/or recurrent solid tumors received three inoculations on days 1,
      22, and 43 at doses of total peptide that ranged from 0.5 to 3.0 mg.
      Immunogenicity was evaluated by enzyme-linked immunosorbent assay, flow
      cytometry, and HER2 signaling assays. Results Twenty-four patients received three
      inoculations at the intended dose levels, which elicited antibodies able to
      recognize native HER2 receptor and inhibited both the proliferation of HER2
      expressing cell lines and phosphorylation of the HER2 protein. The MTD was
      determined to be the highest dose level of 3.0 mg of the combination vaccine.
      There was a significant increase from dose level 1 (0.5 mg) to dose level 4 (3.0
      mg) in HER2-specific antibodies. Four patients (one each with adrenal, colon,
      ovarian, and squamous cell carcinoma of unknown primary) were judged to have
      stable disease; two patients (one each with endometrial and ovarian cancer) had
      partial responses; and 11 patients had progressive disease. Patients with stable
      disease received 6-month boosts, and one patient received a 20-month boost.
      CONCLUSION The combination vaccines were safe and effective in eliciting antibody
      responses in a subset of patients (62.5%) and were associated with no serious
      adverse events, autoimmune disease, or cardiotoxicity. There was preliminary
      evidence of clinical activity in several patients.

PMID- 19752337
TI  - Cancer, clots and consensus: new understanding of an old problem.

PMID- 19752338
TI  - Aromatase inhibitor-induced carpal tunnel syndrome: results from the ATAC trial.
AB  - PURPOSE: Carpal tunnel syndrome (CTS) is a condition in which the median nerve is
      compressed, leading to pain and muscle weakness in the fingers and hand.
      Aromatase inhibitors lead to profound estrogen suppression and may be expected to
      increase the risk of CTS in postmenopausal women receiving adjuvant therapy for
      early breast cancer. PATIENTS AND METHODS: The current analyses were based on the
      100-month median follow-up data in postmenopausal women in the two monotherapy
      arms (anastrozole, n = 3,092; tamoxifen, n = 3,094). Here, we investigate the
      natural history of patients who presented with CTS during adjuvant treatment for
      breast cancer and the relative importance of a range of known risk factors for
      CTS. RESULTS: After 100 months of follow-up, 80 cases (2.6%) of CTS were reported
      in the anastrozole arm, compared with 23 cases (0.7%) in the tamoxifen arm (P <
      .0001). The majority of CTS cases were reported as mild to moderate intensity and
      occurred early. None of the women stopped treatment medication as a result of
      CTS. CTS was significantly increased for women who used prior hormone replacement
      therapy (P = .007) or received prior chemotherapy (P = .01). Those who were 60
      years of age or older at entry were at lower risk of CTS compared with their
      counterparts (P = .002). CONCLUSION: Although the use of anastrozole is
      associated with a greater incidence of CTS, it is rare, and most cases were of
      mild to moderate intensity and short duration. CTS has little impact on the
      overall risk-to-benefit ratio for the use of anastrozole in postmenopausal women
      with early breast cancer.

PMID- 19752339
TI  - Survival disparities in patients with lymphoma according to place of residence
      and treatment provider: a population-based study.
AB  - PURPOSE: Health disparities exist according to an individual's place of
      residence. We evaluated the association between primary area of residence (urban
      v rural) according to treatment provider (university based v community based) and
      overall survival in patients with lymphoma and determined whether there are
      patient groups that could benefit from better coordination of care. PATIENTS AND
      METHODS: Population-based, retrospective cohort study of 2,330 patients with
      centrally confirmed lymphoma from Nebraska and surrounding states and treated by
      university-based or community-based oncologists from 1982 to 2006. RESULTS: Among
      urban residents, 321 (14%) were treated by university-based providers (UUB) and
      816 (35%) were treated by community-based providers (UCB). Among rural residents,
      332 (14%) were treated by university-based providers (RUB), and 861 (37%) were
      treated by community-based providers (RCB). The relative risk (RR) of death among
      UUB, UCB, and RUB were not statistically different. However, RCB had a higher
      risk of death (RR, 1.37; 95% CI, 1.14 to 1.65; P = .01; and RR, 1.26; 95% CI,
      1.06 to 1.49; P = .01) when compared with UUB and RUB, respectively. This
      association was true in both low- and intermediate-risk patients. Among high-risk
      patients, UCB, RUB, and RCB were all at higher risk of death when compared with
      UUB. CONCLUSION: Survival outcomes of patients with lymphoma may be associated
      with place of residence and treatment provider. High-risk patients from rural
      areas may benefit from better coordination of care.

PMID- 19752341
TI  - Estrogen-progestagen menopausal hormone therapy and breast cancer: does delay
      from menopause onset to treatment initiation influence risks?
AB  - PURPOSE: To investigate whether the relation between estrogen-progestagen
      menopausal hormone therapy (EP-MHT) and breast cancer risk varies according to
      the delay between menopause onset and treatment initiation. PARTICIPANTS AND
      METHODS: Between 1992 and 2005, 1,726 invasive breast cancers were identified
      among 53,310 postmenopausal women from the French E3N cohort (mean duration of
      follow-up, 8.1 years). Hazard ratios (HRs) and CIs were estimated using Cox
      models, with MHT never users as the reference. RESULTS: Among recent users of EP
      MHT, the risk of breast cancer varied according to the timing of treatment
      initiation. This variation was confined to short durations of use (< or = 2
      years): the HR was 1.54 (95% CI, 1.28 to 1.86) for short treatments initiated in
      the 3-year period following menopause onset and 1.00 (95% CI, 0.68 to 1.47) for
      short treatments initiated later (P = .04 for homogeneity). However, this pattern
      of risks was not observed in users of EP-MHT containing progesterone, among whom
      there was no significantly increased risk associated with short duration of use
      (HR was 0.87 [95% CI, 0.57 to 1.32] for treatments initiated < or = 3 years after
      menopause, and HR was 0.90 [95% CI, 0.45 to 1.81] for treatments initiated
      later). Longer durations of EP-MHT use were generally associated with increases
      in breast cancer risk, whatever the gap time. CONCLUSION: Our results suggest
      that, for some EP-MHT, the timing of treatment initiation transiently modulates
      the risk of breast cancer and that, when initiated close to menopause, even short
      durations of use are associated with an increased breast cancer risk. Estrogen +
      progesterone combinations might be an exception in this regard.

PMID- 19752340
TI  - Myeloperoxidase genotypes and enhanced efficacy of chemotherapy for early-stage
      breast cancer in SWOG-8897.
AB  - PURPOSE: Myeloperoxidase (MPO) generates reactive oxygen species and also
      activates xenobiotics. In a rigorous clinical trial (Southwest Oncology Group
      SWOG-8897), we examined relationships between genotypes and disease-free survival
      (DFS) among women treated for breast cancer, as well as those who did not receive
      adjuvant chemotherapy. PATIENTS AND METHODS: Patients were assigned to risk
      groups according to standard prognostic features; the low-risk group (n = 753
      genotyped) received follow-up only, and the high-risk group (n = 401 genotyped)
      was randomly assigned to adjuvant cyclophosphamide, methotrexate, and
      fluorouracil (CMF) or cyclophosphamide, doxorubicin, and fluorouracil (CAF), with
      or without tamoxifen. DNA from archived normal lymph node tissue was genotyped,
      and Cox proportional hazard models were used to calculate DFS associated with MPO
      genotypes. RESULTS: Among women in the treatment arm, those with MPO G alleles
      had more than a two-fold reduction in hazard of recurrence (adjusted hazard ratio
      [HR] for GA genotypes, 0.51; 95% CI, 0.21 to 0.99; HR for GG genotypes, 0.41; 95%
      CI, 0.21 to 0.77). Effects were greatest among women who were further randomly
      assigned to tamoxifen (HR for GA genotypes, 0.28; 95% CI, 0.12 to 0.69; HR for GG
      genotypes, 0.19; 95% CI, 0.08 to 0.45). There were no significant associations
      between genotypes and DFS among women in the untreated arm, and relationships
      between genotypes and DFS did not differ by CAF or CMF. CONCLUSION: These
      results, observed in two independent study populations, indicate that high
      activity MPO genotypes are associated with better survival among women receiving
      cyclophosphamide-containing therapy, particularly when followed by tamoxifen
      therapy. MPO can be inhibited and/or upregulated by commonly used drugs; thus,
      our findings merit further investigation for optimization of therapeutics for
      breast cancer.

PMID- 19752342
TI  - Circulating tumor cells: a useful predictor of treatment efficacy in metastatic
      breast cancer.
AB  - PURPOSE: Five or more circulating tumor cells (CTCs) per 7.5 mL of blood predicts
      for poorer progression-free survival (PFS) in patients with metastatic breast
      cancer (MBC). We conducted a prospective study to demonstrate that CTC results
      correlate strongly with radiographic disease progression at the time of and in
      advance of imaging. PATIENTS AND METHODS: Serial CTC levels were obtained in
      patients starting a new treatment regimen for progressive, radiographically
      measurable MBC. Peripheral blood was collected for CTC enumeration at baseline
      and at 3- to 4-week intervals. Clinical outcomes were based on radiographic
      studies performed in 9- to 12-week intervals. RESULTS: Sixty-eight patients were
      evaluable for the CTC-imaging correlations, and 74 patients were evaluable for
      the PFS analysis. Median follow-up was 13.3 months. A statistically significant
      correlation was demonstrated between CTC levels and radiographic disease
      progression in patients receiving chemotherapy or endocrine therapy. This
      correlation applied to CTC results obtained at the time of imaging (odds ratio
      [OR], 6.3), 3 to 5 weeks before imaging (OR, 3.1), and 7 to 9 weeks before
      imaging (OR, 4.9). Results from analyses stratified by type of therapy remained
      statistically significant. Shorter PFS was observed for patients with five or
      more CTCs at 3 to 5 weeks and at 7 to 9 weeks after the start of treatment.
      CONCLUSION: We provide, to our knowledge, the first evidence of a strong
      correlation between CTC results and radiographic disease progression in patients
      receiving chemotherapy or endocrine therapy for MBC. These findings support the
      role of CTC enumeration as an adjunct to standard methods of monitoring disease
      status in MBC.

PMID- 19752343
TI  - Immunophenotypic analysis of AIDS-related diffuse large B-cell lymphoma and
      clinical implications in patients from AIDS Malignancies Consortium clinical
      trials 010 and 034.
AB  - PURPOSE: Diffuse large B-cell lymphoma (DLBCL) represents a clinically
      heterogeneous disease. Models based on immunohistochemistry predict clinical
      outcome. These include subdivision into germinal center (GC) versus non-GC
      subtypes; proliferation index (measured by expression of Ki-67), and expression
      of BCL-2, FOXP1, or B-lymphocyte-induced maturation protein (Blimp-1)/PRDM1. We
      sought to determine whether immunohistochemical analyses of biopsies from
      patients with DLBCL having HIV infection are similarly relevant for prognosis.
      PATIENTS AND METHODS: We examined 81 DLBCLs from patients with AIDS in AMC010
      (cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP] v CHOP
      rituximab) and AMC034 (etoposide, doxorubicin, vincristine, prednisone, and dose
      adjusted cyclophosphamide plus rituximab concurrent v sequential) clinical trials
      and compared the immunophenotype with survival data, Epstein-Barr virus (EBV)
      positivity, and CD4 counts. RESULTS: The GC and non-GC subtypes of DLBCL did not
      differ significantly with respect to overall survival or CD4 count at cancer
      presentation. EBV could be found in both subtypes of DLBCL, although less
      frequently in the GC subtype, and did not affect survival. Expression of FOXP1,
      Blimp-1/PRDM1, or BCL-2 was not correlated with the outcome in patients with AIDS
      related DLBCL. CONCLUSION: These data indicate that with current treatment
      strategies for lymphoma and control of HIV infection, commonly used
      immunohistochemical markers may not be clinically relevant in HIV-infected
      patients with DLBCL. The only predictive immunohistochemical marker was found to
      be Ki-67, where a higher proliferation index was associated with better survival,
      suggesting a better response to therapy in patients whose tumors had higher
      proliferation rates.

PMID- 19752344
TI  - Sonographic and electrodiagnostic evaluations in patients with aromatase
      inhibitor-related arthralgia.
AB  - PURPOSE: To investigate the prevalence of arthralgia in breast cancer patients
      taking aromatase inhibitors (AIs) and perform a detailed rheumatologic assessment
      including autoimmune serology, musculoskeletal sonography, and electromyography
      (EMG) in these patients. PATIENTS AND METHODS: Postmenopausal patients with stage
      I to III breast cancer who were taking adjuvant AIs were enrolled (n = 92).
      Patients who were not receiving hormone treatment were included as a control
      group (n = 28). Musculoskeletal sonography and EMG were applied to the patients
      and the controls along with markers of autoimmunity. RESULTS: Thirty patients
      (32.6%) reported to have AI-related new-onset or worsening arthralgia. The most
      commonly affected joints were knee (70%), wrist (70%), and small joints of the
      hand (63%). Patients taking AIs had increased tendon thicknesses compared with
      those who never received AIs (P < .001). Patients with AI-related arthralgia had
      higher rates of effusion in hand joints/tendons than those without arthralgia (P
      = .033). More patients with AI-related arthralgia had EMG findings consistent
      with carpal tunnel syndrome (CTS) than those without arthralgia (P = .024). No
      significant difference was observed in erythrocyte sedimentation rates, C
      reactive protein, antinuclear antibody, antidouble stranded DNA antibody,
      rheumatoid factor, or anticyclic citrullinated peptide levels between patients
      and controls or between those with and without arthralgia. CONCLUSION: Patients
      with AI-related arthralgia often show tenosynovial changes suggesting
      tenosynovitis, exerting local problems but lacking a systemic inflammatory
      component. Our finding of increased CTS frequency also supports this hypothesis.

PMID- 19752345
TI  - ERG expression is an independent prognostic factor and allows refined risk
      stratification in cytogenetically normal acute myeloid leukemia: a comprehensive
      analysis of ERG, MN1, and BAALC transcript levels using oligonucleotide
      microarrays.
AB  - PURPOSE: Recently, several novel molecular prognostic markers were identified in
      cytogenetically normal acute myeloid leukemia (CN-AML). In addition to the well
      known influence of FLT3, NPM1, and CEBPA mutations, high transcript levels of the
      ERG, BAALC, and MN1 genes have been associated with inferior outcomes, but the
      relative importance of these risk markers remains to be defined. PATIENTS AND
      METHODS: We analyzed ERG, BAALC, and MN1 expression levels in a cohort of 210
      patients with CN-AML who received intensive chemotherapy. Expression levels of
      ERG, BAALC, and MN1 were determined in bone marrow samples by using
      oligonucleotide microarrays. RESULTS: High transcript levels of ERG, BAALC, and
      MN1 were predictors for inferior overall survival (OS) and a lower rate of
      complete remissions (CRs). There were significant positive correlations between
      the expression levels of all three genes. ERG expression levels predicted OS in
      elderly patients (ie, age 60 years or older) with CN-AML (P = .006) as well as in
      younger patients (P = .013). In multivariate analyses, high ERG expression was
      independently associated with a lower CR rate (P = .013), shorter event-free
      survival (P = .008), and shorter OS (P = .005). Patients who had low ERG levels
      and absent FLT3 internal tandem duplication (ITD) had a 5-year OS of 44%, and
      patients who had high ERG expression and FLT3 ITD had a 5-year OS of only 5%.
      CONCLUSION: We analyzed a comprehensive set of molecular risk factors in a large,
      homogeneous CN-AML patient cohort. In this study, high ERG expression levels
      emerged as a strong negative prognostic factor and provided prognostic
      information in addition to established molecular markers.

PMID- 19752346
TI  - Images in cardiovascular medicine: Cor triatriatum dexter mimicking Ebstein
      disease.

PMID- 19752347
TI  - Letter by Modarai et al regarding article, "Contemporary analysis of descending
      thoracic and thoracoabdominal aneurysm repair".

PMID- 19752348
TI  - Letter by Hansel and Simon regarding article, "Body mass index and vigorous
      physical activity and the risk of heart failure among men".

PMID- 19752350
TI  - Comprehensive invasive and noninvasive approach to the right ventricle-pulmonary
      circulation unit: state of the art and clinical and research implications.

PMID- 19752351
TI  - Images in cardiovascular medicine: solitary fatty infiltration within the left
      ventricle detected by cardiac magnetic resonance imaging in a patient presenting
      with ventricular tachycardia.

PMID- 19752353
TI  - Reactive oxygen species-induced stimulation of 5'AMP-activated protein kinase
      mediates sevoflurane-induced cardioprotection.
AB  - BACKGROUND: 5'AMP-activated protein kinase (AMPK), a well-known regulator of
      cellular energy status, is also implicated in ischemic preconditioning leading to
      cardioprotection. We hypothesized that AMPK is involved in anesthetic-induced
      cardioprotection and that this activation is mediated by reactive oxygen species
      (ROS). METHODS AND RESULTS: Isolated Langendorff-perfused rat hearts were
      subjected to 35 minutes of global ischemia (I) followed by 120 minutes of
      reperfusion (I/R). Hearts were assigned to a control group (Con) or a sevoflurane
      (Sevo) group receiving 3 times 5-minute episodes of sevoflurane (2.5vol%) before
      I/R. Phosphorylation of both AMPK and endothelial nitric oxide synthase (eNOS)
      were determined by Western blot analysis. Cardioprotection was assessed after I/R
      from recovery of left ventricular pressure and from infarct size
      (triphenyltetrazolium chloride staining). In the control group, ischemia resulted
      in a 2-fold increase in phosphorylation levels of AMPK (Con 0.13+/-0.01 versus
      Con-I 0.28+/-0.05, P<0.05), which was sustained after 120 minutes of reperfusion
      (Con-I/R 0.26+/-0.02, P<0.05). Sevoflurane preconditioning had no affect on AMPK
      phosphorylation before ischemia (Sevo 0.12+/-0.03, P>0.05), but almost doubled
      the increase in AMPK phosphorylation relative to control after ischemia (Sevo-I
      0.48+/-0.09, P<0.05), an effect that was sustained after reperfusion (Sevo-I/R
      0.49+/-0.12, P<0.05). The AMPK-inhibitor compound C (10 micromol/L) reduced the
      sevoflurane-mediated increase in phosphorylation of AMPK and its target eNOS and
      abolished cardioprotection. The ROS-scavenger n-(2-mercaptopropionyl)-glycine (1
      mmol/L) blunted the sevoflurane-mediated increase in AMPK and eNOS
      phosphorylation and prevented cardioprotection. CONCLUSIONS: Sevoflurane-induced
      AMPK activation protects the heart against ischemia and reperfusion injury and
      relies on upstream production of ROS.

PMID- 19752352
TI  - Peripheral nociception associated with surgical incision elicits remote
      nonischemic cardioprotection via neurogenic activation of protein kinase C
      signaling.
AB  - BACKGROUND: Although remote ischemic stimuli have been shown to elicit
      cardioprotection against ischemia/reperfusion injury, there is little known about
      the effects of nonischemic stimuli. We previously described a remote
      cardioprotective effect of nonischemic surgical trauma (abdominal incision)
      called remote preconditioning of trauma (RPCT). In the present study, we
      elucidate mechanisms underlying this phenomenon. METHODS AND RESULTS: We used a
      murine model of myocardial infarction to evaluate ischemia/reperfusion injury,
      and either abdominal surgical incision, or application of topical capsaicin, to
      elicit cardioprotection. We show that the cardioprotective effect of RPCT is
      initiated by skin nociception, and requires neurogenic signaling involving spinal
      nerves and activation of cardiac sensory and sympathetic nerves. Our results
      demonstrate bradykinin-dependent activation and repression, respectively, of
      PKCepsilon and PKCdelta in myocardium after RPCT, and we show involvement of the
      K(ATP) channels in cardioprotection. Finally, we show that topical application of
      capsaicin, which selectively activates C sensory fibers in the skin, mimics the
      cardioprotective effect of RPCT against myocardial infarction. CONCLUSIONS:
      Nontraumatic nociceptive preconditioning represents a novel therapeutic strategy
      for cardioprotection with great potential clinical utility.

PMID- 19752354
TI  - Mitral repair versus replacement for ischemic mitral regurgitation: comparison of
      short-term and long-term survival.
AB  - BACKGROUND: When compared to mitral valve replacement (MVR), mitral valve repair
      (MVRp) is associated with better survival in patients with organic mitral
      regurgitation (MR). However, there is an important controversy about the type of
      surgical treatment that should be used in patients with ischemic MR. The
      objective of this study was to compare the postoperative outcome of MVRp versus
      MVR in patients with ischemic MR. METHODS AND RESULTS: Preoperative and operative
      data of 370 patients with ischemic MR who underwent mitral valve surgery were
      prospectively collected and retrospectively analyzed. MVRp was performed in 50%
      of patients (n=186) and MVR in 50% (n=184). Although operative mortality was
      significantly lower after MVRp compared to MVR (9.7% versus 17.4%; P=0.03),
      overall 6-year survival was not statistically different between procedures (73+/
      4% versus 67+/-4%; P=0.17). After adjusting for other risk factors and propensity
      score, the type of procedure (MVRp versus MVR) did not come out as an independent
      predictor of either operative (OR, 1.5; 95% CI, 0.7-2.9; P=0.34) or overall
      mortality (HR, 1.2; 95% CI, 0.7-1.9; P=0.52). CONCLUSIONS: As opposed to what has
      been reported in patients with organic MR, the results of this study suggest that
      MVRp is not superior to MVR with regard to operative and overall mortality in
      patients with ischemic MR. These findings provide support for the realization of
      a randomized trial comparing these 2 treatment modalities.

PMID- 19752356
TI  - Effects of preoperative aortic insufficiency on outcome after aortic valve
      sparing surgery.
AB  - BACKGROUND: The presence of significant preoperative aortic insufficiency (AI) or
      the need for cusp repair has been suggested as a risk factor for poorer outcomes
      after aortic valve (AV)-sparing surgery. We analyzed the influence of these
      factors on the mid-term outcomes of AV surgery. METHODS AND RESULTS: Between 1996
      and 2008, 164 consecutive patients underwent elective AV-sparing surgery. Severe
      preoperative AI (grade > or =3+) was present in 93 patients (57%), and 54 (33%)
      had a bicuspid valve. Root repair was performed with either the reimplantation
      (74%) or the remodeling (26%) technique, and cusp repair was performed in 90
      patients (55%). Mean clinical follow-up was 57 months. Hospital mortality was
      0.6%. Cusp repair was required in 52% of the patients with preoperative AI < or
      =2+ and in 57% of those with AI > or =3+ (P=0.6). Cusp repair was required more
      frequently in bicuspid versus tricuspid valves (91% versus 38%, P<0.001). Overall
      survival at 8 years was 88+/-8%. Freedom from AV reoperation at 8 years was
      similar with preoperative AI < or =2+ versus preoperative AI > or =3+ (89+/-11%
      versus 90+/-7%, P=0.7) and with versus without cusp repair (84+/-17% versus 92+/
      8%, P=0.5). Freedom from recurrent AI (grade > or =3+) at 5 years was also
      similar between groups (90+/-10% versus 89+/-8%, P=0.9, and 90+/-8% versus 89+/
      9%, P=0.8, respectively). By multivariate analyses, predictors of recurrent AI >
      or =2+ were preoperative left ventricle end-diastolic diameter and AI >1+ on
      discharge echocardiography. CONCLUSIONS: With a systematic approach to cusp
      assessment and repair, AV-sparing surgery for root pathology has an acceptable
      mid-term outcome, irrespective of preoperative AI or need for cusp repair.

PMID- 19752355
TI  - Significant changes in mitral valve leaflet matrix composition and turnover with
      tachycardia-induced cardiomyopathy.
AB  - BACKGROUND: Dilated cardiomyopathy (DCM) involves significant remodeling of the
      left ventricular-mitral valve (MV) complex, but little is known regarding the
      remodeling of the mitral leaflets. The aim of this study was to assess changes in
      matrix composition and turnover in MV leaflets with DCM. METHODS AND RESULTS:
      Radiopaque markers were implanted in 24 sheep to delineate the MV; 10 sheep
      underwent tachycardia-induced cardiomyopathy (TIC), whereas 14 sheep remained as
      controls. Biplane videofluoroscopy was performed before and after TIC.
      Immunohistochemistry was performed on leaflet cross-sections taken from the
      septal, lateral, anterior, and posterior commissures attachment segments.
      Staining intensity was quantified within each attachment segment and leaflet
      region (basal, mid-leaflet, and free edge). Mitral regurgitation increased from
      0.2+/-0.4 before TIC to 2.2+/-0.9 after TIC (P<0.0002). TIC leaflets demonstrated
      significant remodeling compared to controls, including greater cell density and
      loss of leaflet layered structure (all P<0.05). Collagen and elastic fiber
      turnover was greater in TIC, as was the myofibroblast phenotype (all P<0.05).
      Compositional differences between TIC and control leaflets were heterogeneous by
      annular segment and leaflet region, and related to regional changes in leaflet
      segment length with TIC. CONCLUSIONS: This study shows that the MV leaflets are
      significantly remodeled in DCM with changes in leaflet composition, structure,
      and valve cell phenotype. Understanding how alterations in leaflet mechanics,
      such as those induced by DCM, drive cell-mediated remodeling of the extracellular
      matrix will be important in developing future treatment strategies.

PMID- 19752357
TI  - Long-term survival of the very elderly undergoing aortic valve surgery.
AB  - BACKGROUND: Increasing numbers of the very elderly are undergoing aortic valve
      procedures. We describe the short- and long-term survivorship for this cohort.
      METHODS AND RESULTS: We conducted a cohort study of 7584 consecutive patients
      undergoing open aortic valve surgery without (51.1%; AVR) or with (48.9%; AVR +
      CABG) concomitant coronary artery bypass graft surgery between November 10, 1987
      through June 30, 2006. Patient records were linked to the Social Security
      Administration's Death Master File. Survivorship was stratified by age and
      concomitant CABG surgery. During 39 835 person-years of follow-up, there were
      2877 deaths. Among AVR, there were 3304 patients <80 years of age, 419 patients
      80 to 84 years, and 156 patients > or =85 years (24 patients >90 years). Among
      AVR+CABG patients, there were 2890 patients <80 years of age, 577 patients 80 to
      84 years, and 238 patients > or =85 years (22 patients >90 years). Median
      survivorship for patients undergoing isolated AVR was 11.5 years (<80 years), 6.8
      years (80 to 84 years), 6.2 years (> or =85 years); for patients undergoing
      AVR+CABG, median survivorship was 9.4 years (<80 years), 6.8 years (80 to 84
      years), and 7.1 years (> or =85 years). Among both procedures, adjusted
      survivorship was significantly different across strata of age (P<0.001). These
      findings are similar to life expectancy of the general population from actuarial
      tables: 80 to 84 years (7 years) and > or =85 years (5 years). CONCLUSIONS:
      Survivorship among octogenarians is favorable, with more than half the patients
      surviving more than 6 years after their surgery. Concomitant CABG surgery does
      not diminish median survivorship among patients >80 years of age.

PMID- 19752358
TI  - Survival in patients with severe aortic regurgitation and severe left ventricular
      dysfunction is improved by aortic valve replacement: results from a cohort of 166
      patients with an ejection fraction < or =35%.
AB  - BACKGROUND: Aortic valve replacement (AVR) in patients with severe aortic
      regurgitation (AR) and left ventricular (LV) dysfunction entails a higher
      surgical risk. Though it may improve symptoms and LV size, it is not known
      whether it translates into a survival benefit. METHODS AND RESULTS: This
      retrospective cohort study included patients screened from our echocardiographic
      database between 1993 and 2007 for patients with severe AR and LV ejection
      fraction (EF) < or =35%. Charts reviews were conducted for clinical,
      pharmacological, and surgical information. Mortality data were obtained from the
      social security death index and analyzed as a function of AVR adjusted for the
      propensity score. Of the 785 patients with severe AR, 166 patients had severe LV
      dysfunction defined as an EF < or =35%: 69% of these were men, age 65+/-16 years,
      and LV EF was 23+/-8%. Kaplan-Meier analysis revealed that performance of AVR
      (n=53) was associated with a better survival (P=0.001). Adjusted for the
      propensity score, AVR was associated with a significantly lower mortality hazard
      (HR 0.59, CI 0.42 to 0.98, P=0.04). CONCLUSIONS: There is a clear reluctance to
      offer AVR in a large number of patients with severe AR associated with LV
      dysfunction. However, the performance of AVR in these patients is associated with
      a mortality benefit supporting the current ACC/AHA guidelines.

PMID- 19752359
TI  - The complete supraannular concept: in vivo hemodynamics of bovine and porcine
      aortic bioprostheses.
AB  - BACKGROUND: Complete supraannular placement of an aortic bioprosthesis is one
      approach to optimize the hemodynamic result of an aortic valve replacement. It is
      achieved with the combination of a special valve design and the supraannular
      sewing technique with noneverted mattress sutures. We evaluated 5 bioprostheses
      designed for complete supraannular placement to assess potential hemodynamic
      differences caused by factors (eg, valve material) other than implantation
      position. METHODS AND RESULTS: In 336 patients (mean age, 72.0+/-7.1 years; 143
      women), hemodynamics including mean pressure gradients, effective orifice areas,
      and indices and incidence of patient-prosthesis mismatch were evaluated 6 months
      after surgery. Annulus diameter was measured during surgery. Patients received
      the Carpentier Edwards Perimount Magna (Magna, n=169), the Medtronic Mosaic
      (Mosaic, n=46), the Mosaic Ultra (Ultra, n=17), the SJM Epic Supra (Epic, n=46),
      and the Sorin Soprano (Soprano, n=58). For small annulus sizes (<23 mm), the mean
      pressure gradients of the Magna (11.82+/-4.8 mm Hg) were significantly lower than
      the Mosaic (16.04+/-6.1 mm Hg) and the Ultra (22.0+/-4.1 mm Hg), and the Soprano
      (13.3+/-5.2 mm Hg) was hemodynamically superior to the Ultra. For medium (23 to
      24 mm) and large (>24 mm) annulus sizes, the mean pressure gradients of the Magna
      were lower than the Epic (10.0+/-3.5 mm Hg versus 14.9+/-6.4 mm Hg; 9.9+/-4.0 mm
      Hg versus 18.6+/-12.7 mm Hg). Furthermore, in patients with large annulus size,
      the mean pressure gradients of the Soprano (11.4+/-3.8 mm Hg) were lower compared
      with the Epic (18.5+/-12.7 mm Hg). Severe patient-prosthesis mismatch was
      observed more frequently in patients with the Mosaic (12/46; 26.1%) and the Ultra
      (3/17; 17.6%) prostheses. CONCLUSIONS: Complete supraannular placement cannot
      prevent high pressure gradients or patient-prosthesis mismatch thoroughly, but
      the choice of a bovine prosthesis can optimize hemodynamic performance.

PMID- 19752360
TI  - Autograft reinforcement to preserve autograft function after the ross procedure:
      a report from the german-dutch ross registry.
AB  - BACKGROUND: Autograft reinforcement interventions (R) during the Ross procedure
      are intended to preserve autograft function and improve durability. The aim of
      this study is to evaluate this hypothesis. METHODS AND RESULTS: 1335 adult
      patients (mean age:43.5+/-12.0 years) underwent a Ross procedure (subcoronary,
      SC, n=637; root replacement, Root, n=698). 592 patients received R of the
      annulus, sinotubular junction, or both. Regular clinical and echocardiographic
      follow-up was performed (mean:6.09+/-3.97, range:0.01 to 19.2 years).
      Longitudinal assessment of autograft function with time was performed using
      multilevel modeling techniques. The Root without R (Root-R) group was associated
      with a 6x increased reoperation rate compared to Root with R (Root+R), SC with R
      (SC+R), and without R (SC-R; 12.9% versus 2.3% versus 2.5%.versus 2.6%,
      respectively; P<0.001). SC and Root groups had similar rate of aortic
      regurgitation (AR) development over time. Root+R patients had no progression of
      AR, whereas Root-R had 6 times higher AR development compared to Root+R. In SC, R
      had no remarkable effect on the annual AR progression. The SC technique was
      associated with lower rates of autograft dilatation at all levels of the aortic
      root compared to the Root techniques. R did not influence autograft dilatation
      rates in the Root group. CONCLUSIONS: For the time period of the study surgical
      autograft stabilization techniques preserve autograft function and result in
      significantly lower reoperation rates. The nonreinforced Root was associated with
      significant adverse outcome. Therefore, surgical stabilization of the autograft
      is advisable to preserve long-term autograft function, especially in the Root
      Ross procedure.

PMID- 19752361
TI  - Outcomes of patients undergoing concomitant aortic and mitral valve surgery in
      northern new England.
AB  - BACKGROUND: Concomitant aortic (AV) and mitral (MV) valve surgery accounts for 4%
      of all valve procedures in northern New England. We examined in-hospital and long
      term mortality. METHODS AND RESULTS: This is a report of a prospective study of
      1057 patients undergoing concomitant AV and MV surgery from 1989 to 2007. The
      Social Security Administration Death Master File was used to assess long-term
      survival. Kaplan-Meier and log-rank tests were performed. In-hospital mortality
      was 15.5% (11.0% for patients <70 years, 18.0% for 70- to 79-year-olds, and 24%
      for those > or =80 years). Overall median survival was 7.3 years. Median survival
      without coronary artery bypass grafting was 9.5 years and with coronary artery
      bypass grafting was 5.7 years (P<0.001). Survival in women was worse than in men
      (7.3 versus 9.3, years, P=0.033). Median survival by age was 11.0 years for
      patients <70 years, 5.4 years for 70- to 79-year-olds, and 4.8 years for those >
      or =80 years. Median survival was not significantly different for patients > or
      =80 years compared with those who were 70 to 79 years old (P=0.245). CONCLUSIONS:
      Double-valve surgery has a high in-hospital mortality rate and a median survival
      of 7.3 years. After patients have survived surgery, long-term survival is similar
      between men and women, smaller and larger patients, and those receiving MV repair
      or replacement. Survival continues to decline after surviving surgery for
      patients > or =70 years old and those who undergo concomitant coronary artery
      bypass grafting. In patients <70 years, either mechanical valves in both
      positions or a tissue AV and mitral repair have the lowest in-hospital mortality
      and the best long-term survival. In patients > or =70 years, tissue valves in
      both positions have the best in-hospital and long-term survival.

PMID- 19752362
TI  - Ranolazine as a cardioplegia additive improves recovery of diastolic function in
      isolated rat hearts.
AB  - BACKGROUND: Ranolazine (Ran), an antianginal agent, inhibits late Na(+) current.
      The purpose of this study was to determine whether there was an added benefit of
      adding Ran to cardioplegia (CP) in a model of global ischemia/reperfusion.
      METHODS AND RESULTS: Isolated rat hearts were Langendorff-perfused and exposed to
      40-minute normothermic, cardioplegic global ischemia and 30 minutes of
      reperfusion. Before ischemia and during reperfusion, hearts were treated with no
      drug (control) or with the late Na(+) current inhibitors Ran (5 micromol/L) or
      tetrodotoxin (1 micromol/L). Ischemic cardioplegic arrest led to an increase of
      left ventricular end-diastolic pressure (LVEDP) by > or =20 mm Hg (ie, cardiac
      contracture). Ten out of 11 hearts treated with CP alone developed contracture,
      whereas 6 out of 11 hearts treated with CP plus Ran developed contracture. Ran
      added to CP reduced LVEDP at the end of ischemia from 41+/-5 mm Hg in CP alone to
      26+/-3 mm Hg in CP plus Ran (P=0.024). Area under the curve for LVEDP during the
      entire ischemic period was also smaller in CP plus Ran versus CP alone. The
      percent increase (from baseline) of LVEDP measured at the end of 30-minute
      reperfusion was smaller for CP plus Ran (66+/-18%) versus CP alone (287+/-90%;
      P=0.035). The area under the curve for LVEDP during reperfusion was smaller in CP
      plus Ran versus CP alone. Tetrodotoxin (1 micromol/L) also reduced cardiac
      contracture during ischemia/reperfusion, compared to CP alone. CONCLUSIONS: Our
      results suggest that Ran may have therapeutic potential as an adjunct to CP and
      further support a protective role of Na(+) current inhibition during
      ischemia/reperfusion.

PMID- 19752363
TI  - Prophylactic intravenous magnesium sulphate in addition to oral {beta}-blockade
      does not prevent atrial arrhythmias after coronary artery or valvular heart
      surgery: a randomized, controlled trial.
AB  - BACKGROUND: Atrial arrhythmias (AA) are an important cause of morbidity after
      cardiac surgery. Efforts at prevention of postoperative AA have been suboptimal.
      Perioperative beta-blocker administration is the standard of care at many
      centers. Although prophylactic administration of magnesium sulfate (MgSO(4)) has
      been recommended, review of all previously published trials of MgSO(4) reveals
      conflicting results. This study was designed to address methodological
      shortcomings from previous studies and is the largest randomized, placebo
      controlled trial of intravenous (IV) MgSO(4) for the prevention of AA after
      coronary artery bypass grafting or cardiac valvular surgery. METHODS AND RESULTS:
      A total of 927 nonemergent cardiac surgery patients were stratified into 2
      groups: isolated coronary artery bypass grafting (n=694), or valve surgery with
      or without coronary artery bypass grafting (n=233), and randomized to receive
      either 5g IV MgSO(4) or placebo on removal of the cross-clamp, followed by daily
      4-hour infusions, from postoperative day 1 until postoperative day 4. All
      patients were treated according to an established oral beta-blocker protocol.
      Postoperative serum Mg levels were checked and standard of care was to administer
      IV MgSO(4) for low serum levels. The primary end point was AA lasting > or =30
      minutes or requiring treatment for hemodynamic compromise. There were no
      differences in the incidence of AA between patients who received IV MgSO(4) or
      placebo (26.4% versus 24.3%, respectively). The results were similar when broken
      down according to stratified groups. CONCLUSIONS: In patients treated with a
      protocol for postoperative oral beta-blocker after nonemergent cardiac surgery,
      the addition of prophylactic IV MgSO(4) did not reduce the incidence of AA.

PMID- 19752364
TI  - Preoperative sCD40L levels predict risk of atrial fibrillation after off-pump
      coronary artery bypass graft surgery.
AB  - BACKGROUND: The risk of atrial fibrillation (AF) after coronary bypass surgery
      has been related to redox state, inflammation, and ischemia. Platelet activation
      is common to all of these pathways. We investigated the relation between AF and
      preoperative soluble CD40 ligand (sCD40L), a proinflammatory marker released by
      activated platelets. Furthermore, we studied the role of inflammation,
      endothelial function, and redox state in this relation. METHODS AND RESULTS:
      sCD40L levels were measured in 144 patients in sinus rhythm the day before off
      pump coronary artery surgery. Systemic inflammation was assessed from levels of C
      reactive protein and soluble intercellular adhesion molecule-1, and endothelial
      function was assessed from the brachial artery flow-mediated dilatation response.
      Graft samples were collected during surgery to assess vascular redox state. AF
      occurred in 33% of patients after surgery, with 3% still in AF after 6 weeks.
      Preoperative sCD40L levels were significantly higher in those who developed in
      hospital AF (odds ratio for a 1-SD increase in log[sCD40L]=1.97; 95% CI, 1.21 to
      3.22; P=0.007; after adjustment for age, sex, Euroscore, and total duration of
      operation). sCD40L and vascular superoxide levels were higher in patients still
      in AF at 6 weeks, and endothelial function was lower, although the small number
      of events precluded statistical analysis in this group. Systemic endothelial
      function, redox state, and preoperative markers of systemic inflammation were not
      associated with in-hospital postoperative AF. CONCLUSIONS: Preoperative platelet
      activation, as assessed by sCD40L levels, is a novel predictor of postoperative
      AF, independent of systemic endothelial function, vascular redox state, and
      systemic inflammation.

PMID- 19752365
TI  - Twenty-four-hour holter monitor follow-up does not provide accurate heart rhythm
      status after surgical atrial fibrillation ablation therapy: up to 12 months
      experience with a novel permanently implantable heart rhythm monitor device.
AB  - BACKGROUND: Twenty-four-hour Holter monitoring (24HM) is commonly used to assess
      cardiac rhythm after surgical therapy of atrial fibrillation (AF). However, this
      "snapshot" documentation leaves a considerable diagnostic window and only stores
      short-time cardiac rhythm episodes. To improve accuracy of rhythm surveillance
      after surgical ablation therapy and to compare continuous heart rhythm
      surveillance versus 24HM follow-up intraindividually, we evaluated a novel
      implantable continuous cardiac rhythm monitoring (IMD) device (Reveal XT 9525).
      METHODS AND RESULTS: Forty-five cardiac surgical patients (male 37, mean age
      69.7+/-9.2 years) with a mean preoperative AF duration of 38+/-45 m were treated
      with either left atrial epicardial high-intensity focus ultrasound ablation
      (n=33) or endocardial cryothermy (n=12) in case of concomitant mitral valve
      surgery. Rhythm control readings were derived simultaneously from 24HM and IMD at
      3-month intervals with a total recording of 2021 hours for 24HM and 220 766 hours
      for IMD. Mean follow-up was 8.30+/-3.97 m (range 0 to 12 m). Mean postoperative
      AF burden (time period spent in AF) as indicated by IMD was 37+/-43%. Sinus
      rhythm was documented in 53 readings of 24HM, but in only 34 of these instances
      by the IMD in the time period before 24HM readings (64%, P<0.0001), reflecting a
      24HM sensitivity of 0.60 and a negative predictive value of 0.64 for detecting AF
      recurrence. CONCLUSIONS: For "real-life" cardiac rhythm documentation, continuous
      heart rhythm surveillance instead of any conventional 24HM follow-up strategy is
      necessary. This is particularly important for further judgment of ablation
      techniques, devices as well as anticoagulation and antiarrhythmic therapy.

PMID- 19752366
TI  - Novel implantable device to detect cardiac allograft rejection.
AB  - BACKGROUND: Allograft rejection remains the nemesis of solid organ
      transplantation. Soul Mate is a novel implantable wireless data transmission
      system that analyzes 9 intramyocardial electrogram parameters recorded from 4 or
      6 configurations of 2 or 3 epicardial leads to detect allograft rejection. This
      study determined the ability of the Soul Mate to detect early rejection of
      transplanted hearts. METHODS AND RESULTS: Five dogs underwent heterotopic
      cervical heart transplantation and simultaneous implantation of the Soul Mate's
      Cardiac Rejection Monitoring Device. Dogs were initially immunosuppressed, but
      subsequent drug discontinuation allowed allograft rejection to appear. Allograft
      biopsies were performed at regular intervals to determine rejection grade, which
      was compared to a calculated rejection score determined as percent change from
      baseline of values for each intramyocardial electrogram. There was significant
      correlation between the biopsy results and the evolution of 5 parameters. The
      strongest correlation (r=0.939; P<0.001) was obtained using the "general median"
      parameter from 4 configurations, assessed 1 day before the biopsy, with a
      sensitivity of 85.7% and a specificity of 100% compared to the myocardial biopsy
      results. CONCLUSIONS: The Soul Mate allograft rejection monitoring system
      accurately detected transplanted heart rejection in a canine model noninvasively
      with continuous sampling. This proof-of-concept study suggests that the Soul Mate
      could be used to more intensely and more frequently monitor cardiac allografts
      for rejection.

PMID- 19752367
TI  - Markers of autophagy are downregulated in failing human heart after mechanical
      unloading.
AB  - BACKGROUND: Autophagy is a molecular process that breaks down damaged cellular
      organelles and yields amino acids for de novo protein synthesis or energy
      provision. Mechanical unloading with a left ventricular assist device (LVAD)
      decreases the energy demand of the failing human heart. We tested the hypothesis
      that LVAD support reverses activation of autophagy. METHODS AND RESULTS: Paired
      biopsy samples of left ventricular myocardium were obtained from 9 patients with
      idiopathic dilated cardiomyopathy (mean duration of LVAD support, 214 days) at
      the time of implantation and explantation of the LVAD. Transcript and protein
      levels of markers and mediators of autophagy and apoptosis were measured by
      quantitative reverse-transcription polymerase chain reaction and Western
      blotting. TUNEL assays, C9 immunohistochemistry, and 20S proteasome activity
      assays were also performed. Mechanical unloading significantly decreased mRNA
      transcript levels of Beclin-1, autophagy-related gene 5 (Atg5), and microtubule
      associated protein-1 light chain-3 (MAP1-LC3 or LC3; P<0.02). Protein levels of
      Beclin-1, Atg5-Atg12 conjugate, and LC3-II were also significantly reduced after
      LVAD support (P<0.05). A significant increase in 20S proteasome activity was
      observed with unloading, in parallel to the decrease in autophagic markers.
      Although BNIP3 and the ratio of activated caspase 3 to procaspase 3 increased
      after LVAD support, Bcl-2 and TUNEL-positive nuclei were not significantly
      different between samples. CONCLUSIONS: Mechanical unloading of the failing human
      heart decreases markers of autophagy. These findings suggest that autophagy may
      be an adaptive mechanism in the failing heart, and this phenomenon is attenuated
      by LVAD support.

PMID- 19752368
TI  - Donor serum SMARCAL1 concentrations predict primary graft dysfunction in cardiac
      transplantation.
AB  - BACKGROUND: Primary graft dysfunction (PGD) is a life-threatening complication in
      cardiac transplantation. A sensitive, specific, and easily measurable predictor
      in donors could facilitate PGD prevention. METHODS AND RESULTS: SMARCAL1 is a
      matrix-associated regulator of chromatin with helicase and ATPase activities, and
      its serum concentrations were significantly increased in a targeted protein array
      in donors whose grafts developed PGD. Therefore, this study analyzed SMARCAL1
      serum concentrations by ELISA in 336 heart donors before and after aortic cross
      clamping (ACC) and in recipients at 10, 30, and 60 minutes reperfusion.
      Demographic and hemodynamic parameters of donors and recipients as well as
      transplant procedure characteristics were documented. PGD (n=68) was defined as
      ventricular dilation and hypocontractility associated with systolic blood
      pressure <90 mm Hg, pulmonary capillary wedge pressure >20 mm Hg, and decreased
      mixed venous oxygen saturation necessitating mechanical circulatory support.
      SMARCAL1 serum protein concentration was significantly increased only before and
      after ACC in donors (P<0.0001) whose grafts developed PGD compared to those who
      did not. In receiver operating characteristic curve analysis, SMARCAL1 serum
      concentration at a cut-off level of > or =1.25 ng/mL before ACC in donors
      predicted PGD (P<0.0001, AUC=0.988, OR=17.050, 95% CI=5.200 to 55.901) with 96%
      sensitivity and 88% specificity. SMARCAL1 serum concentrations <1.25 ng/mL in
      donors before ACC resulted in 97% PGD-free outcome and SMARCAL1 concentrations >
      or =1.25 resulted in 83% PGD occurrence. CONCLUSIONS: Donor serum SMARCAL1 may
      serve as a specific, sensitive, and noninvasive predictive marker in the
      assessment of cardiac graft quality.

PMID- 19752369
TI  - Donor pretreatment with hypertonic saline attenuates primary allograft
      dysfunction: a pilot study in a porcine model.
AB  - BACKGROUND: Hypertonic saline (HTS) has been previously demonstrated to have
      immune modulatory and vascular protective effects. We assessed the effect of
      donor pretreatment with HTS on allograft preservation in a porcine model of
      orthotopic heart transplantation. METHODS AND RESULTS: Orthotopic transplants
      were performed after 6 hours of cold static allograft storage. Donor pigs were
      randomly assigned to pretreatment with (n=7) or without (n=6) HTS (4.5 mL/kg of
      7.5% NaCl) administered 1 hour before donor heart arrest. Administration of HTS
      increased serum sodium level from 138+/-2 mmol/L to 154+/-4 mmol/L, which
      normalized to 144+/-3 mmol/L 1 hour after infusion. Successful weaning from
      cardiopulmonary bypass was significantly greater in HTS-treated hearts (6/7 vs
      1/6; P=0.029). Preload recruitable stroke work after transplantation was improved
      compared to control (88+/-21% vs 35+/-8% of baseline; P=0.0001). Similarly, end
      systolic elastance was improved compared to control (85+/-17% vs 42+/-12% of
      baseline; P=0.0002). Posttransplantation systolic blood pressure was
      significantly higher in the donor HTS group (60+/-9 mm Hg vs 35+/-6 mm Hg;
      P=0.04). Donor HTS treatment improved coronary artery endothelial-dependent
      vasorelaxation compared with control (Emax: HTS, 59+/-4%; control, 47+/-3%;
      P=0.04). HTS also resulted in improved endothelial-independent vasorelaxation
      compared with control (Emax: HTS, 71+/-3%; control, 59+/-4%; P=0.03; ED-50: HTS,
      0.56x10 to 6+/-0.23 mol/L; control, 2.5x10 to 6+/-1.0 mol/L; P=0.04). Sensitivity
      to endothelin-1-induced vasospasm was reduced with HTS pretreatment (% maximum
      contraction [Cmax]: HTS, 338+/-15%; control, 419+/-40%; P=0.01). CONCLUSIONS:
      Donor HTS pretreatment attenuates posttransplantation cardiac allograft
      myocardial dysfunction, improves posttransplantation systemic hemodynamic
      function, and preserves posttransplantation cardiac allograft vascular function.
      HTS may be a novel organ donor intervention to prevent primary graft dysfunction.

PMID- 19752370
TI  - Low operative mortality with implantation of a continuous-flow left ventricular
      assist device and impact of concurrent cardiac procedures.
AB  - BACKGROUND: The objective of this study was to determine the impact of concurrent
      cardiac procedures (CCP) on patient outcomes after HeartMate II (HMII) left
      ventricular assist device implantation. METHODS AND RESULTS: Two hundred eighty
      one patients underwent implantation of a HMII as a bridge to transplantation from
      March 2005 to March 2007. One hundred seventy patients had an HMII implanted
      only, and 81 patients underwent concurrent cardiac procedures in conjunction with
      HMII implantation (HMII+CCP). Of these, 47 patients had concurrent valvular
      procedures, 15 patients had simultaneous closure of patent foramen ovale, and 19
      patients had other various cardiac procedures. Patients requiring right
      ventricular assist device support or noncardiac procedures were excluded.
      Preoperative characteristics were similar for patients with and without
      concurrent cardiac procedures. Overall 30-day mortality was 5.8% for the HMII
      group and 11.3% for the HMII+CCP group. Subgroup analysis demonstrated that
      simultaneous patent foramen ovale closure was not associated with an increased 30
      day mortality rate, but concurrent valvular procedures increased the risk to
      8.5%. Patients who underwent an aortic valve procedure had a 30-day mortality
      rate of 25%, higher than for isolated concurrent mitral (0%) or tricuspid repair
      (3.3%). Survival at 180 days was 87% for HMII alone and 80% for HMII+CCP. The
      hazard ratio for concurrent cardiac procedures adjusted for baseline parameters
      was 1.82 (95% CI, 1.07 to 3.10, P=0.026). CONCLUSIONS: There is a low 5.8%
      operative mortality rate for patients requiring uncomplicated HMII implantation,
      with no apparent increased risk for concurrent patent foramen ovale closure or
      mitral or tricuspid repair. However, concurrent aortic valve and other cardiac
      procedures are associated with significantly decreased perioperative and long
      term survival.

PMID- 19752371
TI  - Effect of hypercholesterolemia on myocardial necrosis and apoptosis in the
      setting of ischemia-reperfusion.
AB  - BACKGROUND: Hypercholesterolemia is prevalent in patients who experience
      myocardial ischemia-reperfusion injury (IR). We investigate the impact of dietary
      induced hypercholesterolemia on the myocardium in the setting of acute IR.
      METHODS AND RESULTS: In normocholesterolemic (NC, n=7) and hypercholesterolemic
      (HC, n=7) Yucatan male pigs, the left anterior descending coronary artery was
      occluded for 60 minutes, followed by reperfusion for 120 minutes. Hemodynamic
      values were recorded, and TTC staining was used to assess necrosis. Oxidative
      stress was measured. Specific cell death and survival signaling pathways were
      assessed by Western blot and TUNEL staining. Infarct size was 45% greater in HC
      versus NC (42% versus 61%, P<0.05), whereas the area at risk (AAR) was similar in
      both groups (P=0.61). Whereas global LV function (+dP/dt, P<0.05) was higher
      during entire period of IR in HC versus NC, regional function deteriorated more
      following reperfusion in HC (P<0.05). Ischemia increased indices of myocardial
      oxidative stress such as protein oxidation (P<0.05), lipid peroxidation (P<0.05),
      and nitrotyrosylation in HC versus NC, as well as the expression of phospho-eNOS
      (P<0.05). The expression of myeloperoxidase, p38 MAPK, and phospho-p38 MAPK was
      higher in HC versus NC (all P<05). Ischemia caused higher expression of the
      proapoptotic protein PARP (P<0.05), and lower expression of the prosurvival
      proteins Bcl2 (P<0.05), phospho-Akt, (P<0.05), and phospho-PKCepsilon (P<0.05) in
      the HC versus NC. TUNEL-positive cell count was 3.8-fold (P<0.05) higher in the
      AAR of HC versus NC. CONCLUSIONS: This study demonstrates that experimental
      hypercholesterolemia is associated with increased myocardial oxidative stress and
      inflammation, attenuation of cell survival pathways, and induction of apoptosis
      in the ischemic territory, which together may account for the expansion of
      myocardial necrosis in the setting of acute IR.

PMID- 19752372
TI  - Mesenchymal cell transplantation and myocardial remodeling after myocardial
      infarction.
AB  - BACKGROUND: Targeted delivery of mesenchymal precursor cells (MPCs) can modify
      left ventricular (LV) cellular and extracellular remodeling after myocardial
      infarction (MI). However, whether and to what degree LV remodeling may be
      affected by MPC injection post-MI, and whether these effects are concentration
      dependent, remain unknown. METHODS AND RESULTS: Allogeneic MPCs were expanded
      from sheep bone marrow, and direct intramyocardial injection was performed within
      the borderzone region 1 hour after MI induction (coronary ligation) in sheep at
      the following concentrations: 25x10(6) (25 M, n=7), 75x10(6) (75 M, n=7),
      225x10(6) (225 M, n=10), 450x10(6) (450 M, n=8), and MPC free media only (MI
      Only, n=14). LV end diastolic volume increased in all groups but was attenuated
      in the 25 and 75 M groups. Collagen content within the borderzone region was
      increased in the MI Only, 225, and 450 M groups, whereas plasma ICTP, an index of
      collagen degradation, was highest in the 25 M group. Within the borderzone region
      matrix metalloproteinases (MMPs) and MMP tissue inhibitors (TIMPs) also changed
      in a MPC concentration-dependent manner. For example, borderzone levels of MMP-9
      were highest in the 25 M group when compared to the MI Only and other MPC
      treatment group values. CONCLUSIONS: MPC injection altered collagen dynamics,
      MMP, and TIMP levels in a concentration-dependent manner, and thereby influenced
      indices of post-MI LV remodeling. However, the greatest effects with respect to
      post-MI remodeling were identified at lower MPC concentrations, thus suggesting a
      therapeutic threshold exists for this particular cell therapy.

PMID- 19752373
TI  - Novel minicircle vector for gene therapy in murine myocardial infarction.
AB  - BACKGROUND: Conventional plasmids for gene therapy produce low-level and short
      term gene expression. In this study, we develop a novel nonviral vector that
      robustly and persistently expresses the hypoxia-inducible factor-1 alpha (HIF
      1alpha) therapeutic gene in the heart, leading to functional benefits after
      myocardial infarction. METHODS AND RESULTS: We first created minicircles (MC)
      carrying double-fusion reporter gene consisting of firefly luciferase and
      enhanced green fluorescent protein (Fluc-eGFP) for noninvasive measurement of
      transfection efficiency. Mouse C2C12 myoblasts and normal FVB/N mice were used
      for in vitro and in vivo confirmation, respectively. Bioluminescence imaging
      showed stable MC gene expression in the heart for >12 weeks and the activity
      level was 5.6+/-1.2-fold stronger than regular plasmid at day 4 (P<0.01). Next,
      we created MC carrying HIF-1alpha (MC-HIF-1alpha) therapeutic gene for treatment
      of myocardial infarction. Adult FVB/N mice underwent left anterior descending
      ligation and were injected intramyocardially with: (1) MC-HIF-1alpha; (2) regular
      plasmid carrying HIF-1alpha (PL-HIF-1alpha) as positive control; and (3) PBS as
      negative control (n=10/group). Echocardiographic study showed a significantly
      greater improvement of left ventricular ejection fraction in the MC group
      (51.3%+/-3.6%) compared to regular plasmid group (42.3%+/-4.1%) and saline group
      (30.5%+/-2.8%) at week 4 (P<0.05 for both). Histology demonstrated increased
      neoangiogenesis in both treatment groups. Finally, Western blot showed MC express
      >50% higher HIF-1alpha level than regular plasmid. CONCLUSIONS: Taken together,
      this is the first study to our knowledge to demonstrate that MC can significantly
      improve transfection efficiency, duration of transgene expression, and cardiac
      contractility. Given the serious drawbacks associated with most viral vectors, we
      believe this novel nonviral vector can be of great value for cardiac gene therapy
      protocols.

PMID- 19752374
TI  - Stem cells for myocardial repair with use of a transarterial catheter.
AB  - BACKGROUND: Using a swine model of postinfarction left ventricle (LV) remodeling,
      we investigated marrow-derived, multipotent progenitor cell (MPC) transplantation
      into hearts with acute myocardial infarction (AMI) via a novel transarterial
      catheter. METHODS AND RESULTS: The left anterior descending coronary artery was
      balloon-occluded after percutaneous transluminal angiography to generate AMI (60
      minute no-flow ischemia). The transarterial catheter was then placed in the same
      coronary artery, and either 50x10(6) MPCs (cell group, n=6) or saline (control,
      n=6) was injected into the border zone (BZ) myocardium. LV function was assessed
      by magnetic resonance imaging before AMI and at 1 and 4 weeks after AMI, whereas
      myocardial energy metabolism was assessed by (31)P-magnetic resonance
      spectroscopy at week 4. One week after AMI, the ejection fraction was
      significantly reduced in both groups from a baseline of approximately 50% to
      31.3+/-3.9% (cell group) and 33.3+/-3.1% (control). However, at week 4, the cell
      group had a significant recovery in ejection fraction. The functional
      improvements were accompanied by a significant improvement in myocardial
      bioenergetics. Histologic data demonstrated a 0.55% cell engraftment rate 4 weeks
      after MPC transplantation. Only 2% of engrafted cells were costaining positive
      for cardiogenic markers. Vascular density in the BZ was increased in the cell
      group. Conditioned medium from cultured MPCs contained high levels of vascular
      endothelial growth factor, which was increased in response to hypoxia. MPCs
      cocultured with cardiomyocytes inhibited changes in cardiomyocyte mitochondrial
      membrane potential and cytochrome c release induced by tumor necrosis factor
      alpha. CONCLUSIONS: Thus, a paracrine effect may contribute significantly to the
      observed therapeutic effects of MPC transplantation.

PMID- 19752375
TI  - Hepatocyte growth factor or vascular endothelial growth factor gene transfer
      maximizes mesenchymal stem cell-based myocardial salvage after acute myocardial
      infarction.
AB  - BACKGROUND: Mesenchymal stem cell (MSC)-based regenerative strategies were
      investigated to treat acute myocardial infarction and improve left ventricular
      function. METHODS AND RESULTS: Murine AMI was induced by coronary ligation with
      subsequent injection of MSCs, hepatocyte growth factor (HGF), vascular
      endothelial growth factor (VEGF), or MSCs +HGF/VEGF into the border zone. Left
      ventricular ejection fraction was calculated using micro-computed tomography
      imaging after 6 months. HGF and VEGF protein injection (with or without
      concomitant MSC injection) significantly and similarly improved the left
      ventricular ejection fraction and reduced scar size compared with the MSC group,
      suggesting that myocardial recovery was due to the cytokines rather than
      myocardial regeneration. To provide sustained paracrine effects, HGF or VEGF
      overexpressing MSCs were generated (MSC-HGF, MSC-VEGF). MSC-HGF and MSC-VEGF
      showed significantly increased in vitro proliferation and increased in vivo
      proliferation within the border zone. Cytokine production correlated with MSC
      survival. MSC-HGF- and MSC-VEGF-treated animals showed smaller scar sizes,
      increased peri-infarct vessel densities, and better preserved left ventricular
      function when compared with MSCs transfected with empty vector. Murine
      cardiomyocytes were exposed to hypoxic in vitro conditions. The LDH release was
      reduced, fewer cardiomyocytes were apoptotic, and Akt activity was increased if
      cardiomyocytes were maintained in conditioned medium obtained from MSC-HGF or MSC
      VEGF cultures. CONCLUSIONS: This study showed that (1) elevating the tissue
      levels of HGF and VEGF after acute myocardial infarction seems to be a promising
      reparative therapeutic approach, (2) HGF and VEGF are cardioprotective by
      increasing the tolerance of cardiomyocytes to ischemia, reducing cardiomyocyte
      apoptosis and increasing prosurvival Akt activation, and (3) MSC-HGF and MSC-VEGF
      are a valuable source for increased cytokine production and maximize the
      beneficial effect of MSC-based repair strategies.

PMID- 19752376
TI  - Identification of risk factors related to poor angiogenic potency of bone marrow
      cells from different patients.
AB  - BACKGROUND: Therapeutic angiogenesis induced by the implantation of autologous
      bone marrow-derived cells has been used for the treatment of ischemic diseases.
      However, as the outcomes of cell implantation obviously vary among patients, it
      is essential to identify patients that would benefit the most from this
      treatment. METHODS AND RESULTS: We collected clinical and laboratory data from 25
      patients scheduled to undergo sternotomy for various surgical procedures. Then,
      we aspirated bone marrow cells from the sternum during the operation and
      investigated the cell quality in vitro by cultivation, and their angiogenic
      potency in vivo using an ischemic limb model of mice. The angiogenic potency of
      bone marrow cells differed among patients. Aging, renal failure, anemia, and high
      serum levels of triglyceride, C-reactive protein, interleukin-6, and type I
      collagen cross-linked N-telopeptide (NTX) significantly correlated with poor
      angiogenic potency of bone marrow cells. We assigned scores to these risk
      factors, and found a strong correlation between the risk scores of patients and
      the angiogenic potency of their bone marrow cells (r=-0.883, P<0.001). These risk
      scores can predict the angiogenic potency of bone marrow cells for inducing
      therapeutic angiogenesis with an accuracy of 80%. CONCLUSIONS: We have identified
      the risk factors related to poor angiogenic potency of bone marrow cells and
      developed a new scoring system to predict their angiogenic potency for the
      treatment of ischemic diseases. Our results may help select patients for this
      treatment in future clinical trials.

PMID- 19752377
TI  - Differential effects of mechanical and biological stimuli on matrix
      metalloproteinase promoter activation in the thoracic aorta.
AB  - BACKGROUND: The effect of multiple integrated stimuli on vascular wall expression
      of matrix metalloproteinases (MMPs) remains unknown. Accordingly, this study
      examined the influence of the vasoactive peptide angiotensin II (Ang II) on wall
      tension-induced promoter activation of MMP-2, MMP-9, and membrane type-1 MMP (MT1
      MMP). METHODS AND RESULTS: Thoracic aortic rings harvested from transgenic
      reporter mice containing the MMP-2, MMP-9, or MT1-MMP promoter sequence fused to
      a reporter gene were subjected to 3 hours of wall tension at 70, 85, or 100 mm
      Hg, with or without 100 nM Ang II. Total RNA was harvested from the aortic rings,
      and reporter gene transcripts were quantified by quantitative real-time
      polymerase chain reaction to measure MMP promoter activity. MT1-MMP promoter
      activity was increased at both 85 and 100 mm Hg, compared with baseline tension
      of 70 mm Hg, whereas treatment with Ang II stimulated MT1-MMP promoter activity
      to the same degree at all tension levels (P<0.05). Elevated tension and Ang II
      displayed a potential synergistic enhancement of MMP-2 promoter activation at 85
      and 100 mm Hg, whereas the same stimuli caused a decrease in MMP-9 promoter
      activity (P<0.05) at 100 mm Hg. CONCLUSIONS: This study demonstrated that
      exposure to a relevant biological stimulus (Ang II) in the presence of elevated
      tension modulated MMP promoter activation. Furthermore, these data suggest that a
      mechanical-molecular set point exists for the induction of MMP promoter
      activation and that this set point can be adjusted up or down by a secondary
      biological stimulus. Together, these results may have significant clinical
      implications toward the regulation of hypertensive vascular remodeling.

PMID- 19752378
TI  - Rate of progression and functional significance of aortic root calcification
      after homograft versus freestyle aortic root replacement.
AB  - BACKGROUND: Calcification is an important limitation after aortic root
      replacement. The aims were to compare the long-term degree and rate of
      calcification of homografts versus Medtronic freestyle aortic roots to determine
      the functional consequences and predictive factors. METHODS AND RESULTS: One
      hundred sixty-six patients were prospectively randomized to undergo homograft
      versus freestyle total aortic root replacement. Of those, 98 patients underwent a
      total of 248 electron beam computed tomography studies at 0.5, 1, 1.5, 2, 3, and
      8 years. All patients underwent yearly clinical and echocardiographic follow-up.
      Calcium scores were measured using Agatston scoring. Mixed effects models
      demonstrate significantly higher calcium scores in homograft roots than freestyle
      at 1.5 years (P=0.02), 2 years (P=0.02), and 3 years (P=0.01), with a trend at 1
      year (P=0.06) and 8 years (P=0.1). Homograft calcification occurs significantly
      faster than in freestyle prostheses between 6 months and 3 years after surgery
      (P=0.02). Calcification occurs at a similar rate thereafter up to 8 years
      (P=0.3). At 8 years, freedom from aortic valve dysfunction was lower in
      homografts than freestyle roots (P=0.06). Freedom from reoperation was 93+/-4% in
      the homograft group versus 100+/-0% in the freestyle group at 8 years (P=0.01).
      On multivariate analysis, redo surgery (P<0.001), smoking (P<0.01), atrial
      fibrillation (P=0.001), family history of coronary artery disease (P<0.01), and a
      degenerative etiology (P=0.02) were predictive of higher calcium scores.
      CONCLUSIONS: Homograft roots exhibit significantly higher calcium scores than
      freestyle roots because of faster early calcification.

PMID- 19752379
TI  - Retrograde ascending aortic dissection during or after thoracic aortic stent
      graft placement: insight from the European registry on endovascular aortic repair
      complications.
AB  - BACKGROUND: Single-center reports have identified retrograde ascending aortic
      dissection (rAAD) as a potentially lethal complication of thoracic endovascular
      aortic repair (TEVAR). METHODS AND RESULTS: Between 1995 and 2008, 28 centers
      participating in the European Registry on Endovascular Aortic Repair
      Complications reported a total of 63 rAAD cases (incidence, 1.33%; 95% CI, 0.75
      to 2.40). Eighty-one percent of patients underwent TEVAR for acute (n=26, 54%) or
      chronic type B dissection (n=13, 27%). Stent grafts with proximal bare springs
      were used in majority of patients (83%). Only 7 (15%) patients had intraoperative
      rAAD, with the remaining occurring during the index hospitalization (n=10, 21%)
      and during follow-up (n=31, 64%). Presenting symptoms included acute chest pain
      (n=16, 33%), syncope (n=12, 25%), and sudden death (n=9, 19%) whereas one fourth
      of patients were asymptomatic (n=12, 25%). Most patients underwent emergency
      (n=25) or elective (n=5) surgical repair. Outcome was fatal in 20 of 48 patients
      (42%). Causes of rAAD included the stent graft itself (60%), manipulation of
      guide wires/sheaths (15%), and progression of underlying aortic disease (15%).
      CONCLUSIONS: The incidence of rAAD was low (1.33%) in the present analysis with
      high mortality (42%). Patients undergoing TEVAR for type B dissection appeared to
      be most prone for the occurrence of rAAD. This complication occurred not only
      during the index hospitalization but after discharge up to 1050 days after TEVAR.
      Importantly, the majority of rAAD cases were associated with the use of proximal
      bare spring stent grafts with direct evidence of stent graft-induced injury at
      surgery or necropsy in half of the patients.

PMID- 19752380
TI  - Comparison of ascending aorta versus femoral artery cannulation for acute aortic
      dissection type A.
AB  - BACKGROUND: The site of cannulation for repair of ascending aortic dissection
      remains controversial. We present our experience with ascending aortic
      cannulation for acute aortic dissection type A. METHODS AND RESULTS: From January
      1988 to September 2007, we operated on 242 patients for acute aortic dissection
      type A. Medical records of 235 patients who received ascending aortic cannulation
      or femoral cannulation were retrospectively reviewed. Long-term follow-up was
      complete in 97% of patients. Cannulation was accomplished in 82 patients through
      the ascending aorta and in 153 patients through the femoral artery. Preoperative
      patient characteristics were almost comparable between groups. Similarly, there
      were no differences in preoperative patient characteristics and intraoperative
      parameters including operation time, bypass time, cross-clamp time, hypothermic
      circulatory arrest time, and percentage of total arch replacement. The 30-day
      mortality rate was 14% in the aortic group and 23% in the femoral group (P=0.07),
      and incidence of stroke was 4.9% in the aortic group and 4.5% in the femoral
      group (P=0.86). During follow-up (mean, 5.5 years), survival at 5 years and 10
      years was 65% and 41% in the aortic group and 64% and 46% in the femoral group,
      respectively (P=0.97). CONCLUSIONS: The cannulation site should be chosen
      according to the patient's pathology and status, and the present study suggests
      that ascending cannulation in patients with acute aortic dissection type A can be
      a safe alternative, offering acceptable early and long-term outcomes.

PMID- 19752381
TI  - Acute type A intramural hematoma: analysis of current management strategy.
AB  - BACKGROUND: Management of acute type A intramural hematoma (IMH) remains
      controversial, varying from immediate surgery to medical management only.
      Conversion to typical dissection remains a concern. We analyzed our experience
      managing acute type A IMH. METHODS AND RESULTS: Between October 1999 and May
      2008, 251 patients with acute type A aortic dissection were treated, including 36
      (14.3%) with type A IMH. Seven IMH patients (19%) were repaired immediately, 28
      (80%) managed initially with optimal medical management and eventual repair and 1
      (3%) with medical management only. End points analyzed were early mortality and
      conversion to typical dissection (flow in the false lumen of the ascending
      aorta). Time (hours) from onset of symptoms defined initiation of IMH. Early
      mortality for acute type A IMH was 8.3% (3/36): 14.3% (1/7) with immediate repair
      and 7.1% (2/28) when optimal medical management with eventual repair was
      undertaken (P=0.69). The 1 medically managed Asian patient survived with
      resolution of the IMH. Conversion to type A IMH to typical dissection occurred in
      33% (12/36) of cases. No conversions were observed within 72 hours. Aortic
      diameter did not predict conversion. In actuarial analysis among the initially
      medically managed group with eventual repair, the hazard conversion to typical
      dissection increased significantly at 8 days from the onset of symptoms (P<0.05).
      CONCLUSIONS: Despite optimal medical management, conversion of type A IMH to
      typical dissection still remains a concern, with the most significant risk beyond
      8 days. In our patient population, timely surgical repair is recommended.

PMID- 19752382
TI  - Clinical outcomes of medical therapy and timely operation in initially diagnosed
      type a aortic intramural hematoma: a 20-year experience.
AB  - BACKGROUND: The management of aortic intramural hematoma (IMH) involving the
      ascending aorta (type A) has not been well-established. The purpose of this study
      was to clarify the long-term clinical outcomes of patients with type A IMH who
      were treated with medical therapy and timely operation. METHODS AND RESULTS:
      Clinical data including operative mortality, IMH-related events, and long-term
      survival were retrospectively reviewed in 66 patients with type A IMH, who were
      admitted to our institution from 1986 to 2006. Emergent surgical repair was
      performed in 16 (24%) patients because of severe complications, whereas 50
      patients were treated with initial medical therapy. In medically treated
      patients, 15 (30%) patients who demonstrated progression to classic dissection or
      increase in hematoma size within 30 days underwent surgical repair except for 2
      patients who refused surgery. The 30-day mortality rate was 6% with emergent
      surgery and 4% with supportive medial therapy. There were 7 late deaths and the
      actuarial survival rates of all patients were 96+/-3%, 94+/-3%, and 89+/-5% at 1,
      5, and 10 years, respectively. In medically treated patients, maximum aortic
      diameter was the only predictor of early and late progression of ascending IMH
      (hazard ratio, 4.43; 95% CI, 2.04-9.64; P<0.001). Aortic diameter > or =50 mm
      predicted progression of ascending IMH with the positive and negative value of
      83% and 84%, respectively. CONCLUSIONS: Combination of medical therapy and timely
      operation resulted in favorable long-term clinical outcomes in patients with type
      A IMH.

PMID- 19752383
TI  - Phosphodiesterase-5 inhibitor, tadalafil, protects against myocardial
      ischemia/reperfusion through protein-kinase g-dependent generation of hydrogen
      sulfide.
AB  - BACKGROUND: Tadalafil is a novel long-acting inhibitor of phosphodiesterase-5.
      Because cGMP-dependent protein kinase (PKG) signaling plays a key role in
      cardioprotection, we hypothesized that PKG activation with tadalafil would limit
      myocardial ischemia/reperfusion (I/R) injury and dysfunction. Additionally, we
      contemplated that cardioprotection with tadalafil is mediated by hydrogen sulfide
      (H(2)S) signaling in a PKG-dependent fashion. METHODS AND RESULTS: After baseline
      transthoracic echocardiography (TTE), adult ICR mice were injected i.p. with
      vehicle (10% DMSO) or tadalafil (1 mg/kg) with or without KT5823 (KT, PKG
      blocker, 1 mg/kg) or dl-propargylglycine (PAG, Cystathionine-gamma-lyase [CSE,
      H(2)S-producing enzyme] blocker; 50 mg/kg) 1 hour before coronary artery ligation
      for 30 minutes and reperfusion for 24 hours, whereas C57BL wild-type and CSE
      knockout mice were treated with either vehicle or tadalafil. After reperfusion,
      TTE was performed and hearts were collected for infarct size (IS) measurement
      using TTC staining. Survival was increased with tadalafil (95%) compared with
      control (65%, P<0.05). Infarct size was reduced with tadalafil (13.2+/-1.7%)
      compared to vehicle (40.6+/-2.5%; P<0.05). KT and PAG abolished tadalafil-induced
      protection (IS: 39.2+/-1% and 51.2+/-2.4%, respectively) similar to genetic
      deletion of CSE (47.2+/-5.1%). Moreover, tadalafil preserved fractional
      shortening (FS: 31+/-1.5%) compared to control (FS: 22+/-4.8%, P<0.05). Baseline
      FS was 44+/-1.7%. KT and PAG abrogated the preservation of LV function with
      tadalafil by decline in FS to 17+/-1% and 23+/-3%, respectively. Compared to
      vehicle, myocardial H(2)S production was significantly increased with tadalafil
      and was abolished with KT. CONCLUSIONS: PKG activation with tadalafil limits
      myocardial infarction and preserves LV function through H(2)S signaling.

PMID- 19752384
TI  - Paclitaxel-eluting biodegradable synthetic vascular prostheses: a step towards
      reduction of neointima formation?
AB  - BACKGROUND: Clinical small-caliber vascular prostheses are unsatisfactory.
      Reasons for failure are early thrombosis and late intimal hyperplasia. We thus
      prepared biodegradable small-caliber vascular prostheses using electrospun
      polycaprolactone (PCL) with slow-releasing paclitaxel (PTX), an antiproliferative
      drug. METHODS AND RESULTS: PCL solutions containing PTX were used to prepare
      nonwoven nanofibre-based 2-mm ID prostheses. Mechanical morphological properties
      and drug loading, distribution, and release were studied in vitro. Infrarenal
      abdominal aortic replacement was carried out with nondrug-loaded and drug-loaded
      prostheses in 18 rats and followed for 6 months. Patency, stenosis, tissue
      reaction, and drug effect on endothelialization, vascular remodeling, and
      neointima formation were studied in vivo. In vitro prostheses showed controlled
      morphology mimicking extracellular matrix with mechanical properties similar to
      those of native vessels. PTX-loaded grafts with suitable mechanical properties
      and controlled drug-release were obtained by factorial design. In vivo, both
      groups showed 100% patency, no stenosis, and no aneurysmal dilatation.
      Endothelial coverage and cell ingrowth were significantly reduced at 3 weeks and
      delayed at 12 and 24 weeks in PTX grafts, but as envisioned, neointima formation
      was significantly reduced in these grafts at 12 weeks and delayed at 6 months.
      CONCLUSIONS: Biodegradable, electrospun, nanofibre, polycaprolactone prostheses
      are promising because in vitro they maintain their mechanical properties
      (regardless of PTX loading), and in vivo show good patency, reendothelialize, and
      remodel with autologous cells. PTX loading delays endothelialization and cellular
      ingrowth. Conversely, it reduces neointima formation until the end point of our
      study and thus may be an interesting option for small caliber vascular grafts.

PMID- 19752385
TI  - The functional intraoperative pulmonary blood flow study is a more sensitive
      predictor than preoperative anatomy for right ventricular pressure and
      physiologic tolerance of ventricular septal defect closure after complete
      unifocalization in patients with pulmonary atresia, ventricular septal defect,
      and major aortopulmonary collaterals.
AB  - BACKGROUND: The objective was to determine if intraoperative pulmonary artery
      (PA) flow studies after complete unifocalization correlate with postrepair
      hemodynamics for pulmonary atresia (PA), ventricular septal defects (VSD), and
      major aortopulmonary collaterals. METHODS AND RESULTS: Twenty patients (median
      age, 8 months; weight, 7.9 kg) underwent unifocalization between 2003 and 2008. A
      functional PA flow study was achieved by cannulating the unifocalized central PA
      before intracardiac repair and increasing flow incrementally to 2.5 L/min per
      m(2). Mean PA pressure (mPAP) was measured. The intent was to close the VSD for a
      mPAP of <30 mm Hg. Right ventricular systolic pressure (RVSP) and systemic
      systolic pressure were recorded. Total incorporated pulmonary segments, pulmonary
      segment artery ratio (ratio of incorporated segments to 18), and total
      neopulmonary artery index (the sum of major aortopulmonary collaterals and native
      PA index) were calculated. The VSD was successfully closed in 18 patients (90%).
      One attempted closure required an intraoperative fenestration. The study mPAP
      correlated with RVSP (rho=0.72; P=0.0027) and RVSP/systemic systolic pressure
      (rho=0.67; P=0.0063). Total neopulmonary artery index had a nonsignificant
      negative correlation with RVSP (rho=-0.42; P=0.079). Total incorporated pulmonary
      segments and pulmonary segment artery ratio were not correlated. Flow study mPAP
      had the highest accuracy in predicting successful VSD closure: area under the
      receiver-operator curve (0.83) versus total neopulmonary artery index (0.42),
      pulmonary segments (0.35), and pulmonary segment artery ratio (0.33).
      CONCLUSIONS: The intraoperative pulmonary flow study predicted postoperative
      physiology significantly better than did standard anatomic measures. Conventional
      measures should be used with caution when determining the possibility for
      complete repair.

PMID- 19752386
TI  - Outcomes after anatomic repair for d-transposition of the great arteries with
      left ventricular outflow tract obstruction.
AB  - BACKGROUND: D-transposition of the great arteries (TGA) with left ventricular
      outflow tract obstruction (LVOTO) may be treated with arterial switch operation
      (ASO) with or without LVOT intervention, as well as non-ASO anatomic repairs,
      such as aortic translocation or Rastelli procedure. We evaluated midterm results
      of repair for TGA/LVOTO at our institution. METHODS AND RESULTS: Eighty-eight
      patients with TGA/LVOTO who underwent anatomic repair were retrospectively
      reviewed. LVOTO was defined as pulmonary valve (PV) z-score < or =-2.0 or LVOT
      gradient > or =20 mm Hg in the presence of anatomic subvalvar stenosis. Risk
      factors for LVOT reintervention were determined by logistic regression. There was
      no hospital mortality and 1 late mortality. Patients undergoing Rastelli
      procedure were more likely to require surgical reintervention for LVOTO compared
      to the other groups (P=0.015). Patients undergoing ASO alone had a higher rate of
      late LVOT reintervention compared to those who had concomitant ASO/LVOT
      intervention (P=NS). In those undergoing Rastelli, a larger PV z-score was a
      predictor of LVOT reintervention (P=0.012). PV z-scores significantly decreased
      before repair in patients undergoing delayed repair (P=0.005); however, they
      increased significantly after neonatal ASO (P<0.001). CONCLUSIONS: Patients with
      TGA/LVOTO who undergo Rastelli repair have a high rate of LVOT reintervention.
      Higher preoperative PV z-score is a risk factor for reintervention in this group.
      Patients with mild/moderate LVOTO undergoing ASO alone without LVOT intervention
      may have an increased risk of LVOT reintervention. In neonates who are candidates
      for ASO, delay of repair is associated with diminution in size of PV, which may
      subsequently reduce their suitability for ASO.

PMID- 19752387
TI  - Racial disparity persists after on-pump and off-pump coronary artery bypass
      grafting.
AB  - BACKGROUND: Race has been shown to be an independent risk factor for operative
      mortality after coronary artery bypass grafting (CABG). This study sought to
      determine the extent to which race is a risk factor for adverse events, long-term
      mortality, and whether off-pump surgery (OPCAB) modifies that risk. METHODS AND
      RESULTS: The Society of Thoracic Surgeons Adult Cardiac Database at Emory
      Healthcare affiliated hospitals was queried for all primary isolated CABG records
      from 1997 to 2007. A propensity score was formulated to balance the patient
      groups with respect to treatment assignment (OPCAB or CABG on cardiopulmonary
      bypass). Multivariable logistic regression was used to assess the impact of black
      race and OPCAB on in-hospital outcomes (death, stroke, myocardial infarction, and
      their composite, major adverse cardiac events). Cox proportional hazards
      regression model and Kaplan-Meier curves determined whether black race affected
      long-term all-cause mortality. Interaction terms were constructed to test whether
      OPCAB surgery influences surgical results differently in black patients than in
      white patients. There were 12 874 consecutive CABG patients, including 2033
      (15.8%) blacks and 10 841 (84.2%) whites. Survival at 3, 5, and 10 years for
      blacks (87.5%, 81.4%, 63.8%) was significantly lower than for whites (90.7%,
      85.2%, 67.1%, P<0.001). Blacks (adjusted odds ratio, 0.77; 95% CI, 0.44 to 1.36)
      and whites (adjusted odds ratio, 0.72; 95% CI, 0.53 to 0.99) who had OPCAB had
      lower risk-adjusted odds of major adverse cardiac events than their racial
      counterparts who had CABG on cardiopulmonary bypass. CONCLUSIONS: Short- and long
      term outcomes are significantly worse in black than in white patients undergoing
      primary isolated CABG. OPCAB does not narrow the disparity in outcomes between
      blacks and whites.

PMID- 19752388
TI  - Evaluation of revascularization subtypes in octogenarians undergoing coronary
      artery bypass grafting.
AB  - BACKGROUND: Recent data suggest that octogenarians' long-term survival after
      complete coronary artery bypass graft revascularization is superior to incomplete
      revascularization. Discriminating between variable definitions of "complete"
      complicates interpretation of survival data. We aimed to clarify octogenarian
      long-term survival rates by stratifying revascularization subtypes. METHODS AND
      RESULTS: From 1986 to 2007, 580 patients 80 to 94 years of age underwent coronary
      artery bypass graft. Functional complete revascularization was defined as at
      least 1 graft to all diseased coronary vessels with >50% stenosis. Traditional
      complete revascularization was defined as 1 graft to each major arterial system
      with at least 50% stenosis. Incomplete revascularization was defined as leaving
      diseased, ungrafted regions. Revascularization was functional in 279 (48%),
      traditional in 181 (31%), and incomplete in 120 (21%). Long-term survival was
      evaluated by Kaplan-Meier analysis. Of 537 operative survivors, there were 402
      late deaths. Cumulative long-term survival totaled 2890 patient-years. Late
      survival (Kaplan-Meier) was similar between functional (mean, 6.8 years) and
      traditional (6.7 years) groups (P=0.51), but diminished with incomplete (4.2
      years) revascularization (P=0.007). Survival by group at 5 years was: 59+/-3%
      functional, 57+/-4% traditional, and 45+/-5% incomplete. Survival at 8 years was:
      40+/-3% functional, 37+/-4% traditional, and 26+/-5% incomplete. To minimize
      selection bias in patients with limited life expectancy, Kaplan-Meier analysis
      was repeated including only patients with survival >12 months. Survival was again
      impaired with incomplete revascularization (P=0.04), and there was no difference
      between functional and traditional complete revascularization (P=0.73).
      CONCLUSIONS: Bypassing all diseased arterial vessels after revascularization does
      not afford significant long-term survival advantage compared to a traditional
      approach. Incomplete revascularization, related to more extensive disease, is
      associated with an 18% decline in survival. These data suggest that it is
      important to avoid incomplete revascularization in octogenarians, but the
      supplementary endeavor required to perform functional complete revascularization
      does not improve survival.

PMID- 19752389
TI  - Does reasonable incomplete surgical revascularization affect early or long-term
      survival in patients with multivessel coronary artery disease receiving left
      internal mammary artery bypass to left anterior descending artery?
AB  - BACKGROUND: The objective was to evaluate the impact of complete
      revascularization (CR) versus reasonable incomplete surgical revascularization
      (IR) in others than left anterior descending artery territory on early and late
      survival in patients with multivessel coronary artery disease (CAD). METHODS AND
      RESULTS: During a 7-year period, 8.806 consecutive patients with multivessel CAD
      affecting the proximal left anterior descending artery or left main stem
      underwent sternotomy for isolated coronary artery bypass grafting including left
      internal mammary artery-left anterior descending artery bypass. A total of 936
      patients (10.6%) had IR of the circumflex or right coronary artery territory. IR
      was based on the traditional classification. Follow-up was 3.5+/-2.2 years.
      Patient groups were comparable regarding age (CR 67.1 versus IR 67.6 years),
      ejection fraction (57.2% versus 57.5%), and logEuroscore (4.5% versus 4.5%).
      Patients receiving IR presented with more complex CAD. Mean number of distal
      anastomoses was 3.0+/-0.8 CR versus 2.4+/-0.6 IR. Operation time (176 versus 187
      minutes) and cross-clamp time (52 versus 56 minutes) were longer in the IR group
      (P<0.001). Hospital mortality was 3.3% CR versus 3.2% IR (P=0.520). Independent
      risk factors for hospital mortality were age, pulmonary hypertension, chronic
      obstructive pulmonary disease, peripheral vascular disease, and emergency
      indication, but not IR (P=0.922). Arterial revascularization was protective.
      Cumulative survival at 1-year was 93.1% CR versus 93.6% IR and at 5 years 82.2 CR
      versus 80.9% IR (P=0.457). CONCLUSIONS: In presence of left internal mammary
      artery-to-left anterior descending artery bypass, reasonable IR of the circumflex
      or right coronary artery territory did not adversely affect early or long-term
      survival in patients with multivessel CAD. In patients presenting with 1 poor
      target vessel; however, IR is a good therapeutic option and the benefit of CR
      should be balanced against the risks.

PMID- 19752390
TI  - Minimally invasive coronary artery bypass grafting: dual-center experience in 450
      consecutive patients.
AB  - BACKGROUND: Minimally invasive coronary artery bypass grafting (MICS CABG) is a
      novel coronary operation that does not require infrastructure and is potentially
      available to all cardiac surgeons. It aims at decreasing the invasiveness of
      conventional CABG while preserving the applicability and durability of surgical
      revascularization. We examined the feasibility and safety of MICS CABG in the
      first large series of this operation to date. METHODS AND RESULTS: All myocardial
      territories are accessed via a 4- to 6-cm left fifth intercostal thoracotomy. An
      apical positioner and epicardial stabilizer are introduced into the chest through
      the subxyphoid and left seventh intercostal spaces, respectively. The left
      internal thoracic artery is used to graft the left anterior descending artery,
      and radial artery or saphenous vein segments are used to graft the lateral and
      inferior myocardial territories. Proximal anastomoses are performed directly onto
      the aorta or from the left internal thoracic artery as a T-graft. In the first
      450 consecutive MICS CABG procedures at our 2 centers, mean+/-SD age was 62.3+/
      10.7 years and 123 patients were female (27%). The average number of grafts was
      2.1+/-0.7, with complete revascularization in 95% of patients. There were 34
      patients in whom cardiopulmonary bypass was used (7.6%), 17 conversions to
      sternotomy (3.8%), and 10 reinterventions for bleeding (2.2%). Perioperative
      mortality occurred in 6 patients (1.3%). CONCLUSIONS: MICS CABG is feasible and
      has excellent procedural and short-term outcomes. This operation could
      potentially make multivessel minimally invasive coronary surgery safe, effective,
      and more widely available.

PMID- 19752391
TI  - RING+STRING: Successful repair technique for ischemic mitral regurgitation with
      severe leaflet tethering.
AB  - BACKGROUND: Residual/recurrent mitral valve regurgitation is observed in 30%
      after undersized ring annuloplasty (RING) for ischemic mitral regurgitation
      (IMR). RING addresses primarily annular dilatation but does not correct severe
      leaflet tethering attributable to papillary muscle (PM) displacement. We proposed
      adjunctive PM repositioning under transesophageal echocardiography (TEE) guidance
      in the loaded beating heart using a transventricular suture (STRING). METHODS AND
      RESULTS: Patients with tenting height > or =10 mm were identified as high-risk
      patients for repair failure. In these patients (n=30, age 68+/-11 years, ejection
      fraction 37+/-14%), RING (partial, median 29 mm) was combined with the adjunctive
      STRING-technique. A Teflon-pledgeted 3-0-polytetrafluoroethylene-suture was
      anchored in the posterior PM via horizontal aortotomy, exteriorized through the
      aorto-mitral continuity, and tied in the loaded beating heart under TEE guidance.
      Tenting height (14+/-2 mm versus 6+/-1 mm, P<0.001) and tenting area (3.9+/-0.9
      cm(2) versus 1.0+/-0.2 cm(2), P<0.001) decreased. The distance between pPM and
      aorto-mitral continuity decreased (44+/-4 mm versus 37+/-3 mm, P<0.001). Survival
      at 2 years was similar compared with a historical matched control-group (89%
      versus 73%, P=0.13), whereas freedom from MR>II was higher in the RING+STRING
      group (94% versus 71%, P=0.01). End-diastolic (61.7+/-7.2 mm versus 54.8+/-9.2
      mm, P<0.001) and end-systolic (48.5+/-8.5 mm versus 42.7+/-7.8 mm, P=0.002)
      ventricular diameters decreased in the RING+STRING-group but persisted in the
      control-group (60.4+/-7.8 mm versus 58.9+/-7.5 mm, P=0.38; 47.8+/-9.6 mm versus
      48.3+/-9.5 mm, P=0.52). During follow-up (median 26 months) only 1 patient of the
      study-group required reoperation for degenerative MR, while 2 control-group
      patients underwent reoperation for recurrent functional MR. CONCLUSIONS: Our
      novel approach for IMR attenuates high risk of repair failure in patients with
      severe leaflet tethering and results in reverse remodeling.

PMID- 19752392
TI  - Impact of papillary muscle relocation as adjunct procedure to mitral ring
      annuloplasty in functional ischemic mitral regurgitation.
AB  - BACKGROUND: The optimal surgical treatment in functional ischemic mitral
      regurgitation (FIMR) remains controversial. Recently, a posterior papillary
      muscle relocation (PMR) technique as adjunct procedure to ring annuloplasty has
      been proposed to prevent recurrent FIMR. In the present study, we used 3D cardiac
      MRI to assess the impact of relocating both papillary muscles as adjunct
      procedure to downsized ring annuloplasty on mitral leaflet coaptation geometry in
      FIMR pigs. METHODS AND RESULTS: Eleven FIMR pigs were randomized to downsized
      ring annuloplasty (RA; n=6) or RA combined with PMR (RA+PMR, n=5). In the RA+PMR
      group, a 2-0 Gore-Tex suture was attached to each trigone, exteriorized through
      the corresponding papillary muscle, mounted on an epicardial pad, and tightened
      to relocate the myocardium adjacent to the anterior and posterior papillary
      muscles 5 and 15 mm, respectively. Using 3D MRI, the impact from these
      interventions on leaflet geometry was assessed. The distance from the posterior
      papillary muscle to the anterior trigone was reduced significantly more (median
      values) in the RA+PMR compared with RA animals at end-diastole (-7.9% versus
      3.8%, P<0.01) and end-systole (-9.7% versus 2.5%, P=0.02). Accordingly, lateral
      tethering of the coaptation point (median values) was reduced significantly more
      in RA+PMR compared with RA animals (-42.8% versus -29.1%, P<0.01). CONCLUSIONS:
      Adding papillary muscle relocation to downsized ring annuloplasty reduced lateral
      leaflet tethering in a porcine experimental model of FIMR. Therefore, this
      technique holds promise for reducing persistent and recurrent FIMR in patients.

PMID- 19752393
TI  - Mitral leaflet adaptation to ventricular remodeling: prospective changes in a
      model of ischemic mitral regurgitation.
AB  - BACKGROUND: Ischemic mitral regurgitation is caused by systolic traction on the
      mitral leaflets related to ventricular distortion. Little is known about how
      chronic tethering affects leaflet area, in part because it cannot be measured
      repeatedly in situ. Recently, a new method for 3D echocardiographic measurement
      of mitral leaflet area was developed and validated in vivo against sheep valves,
      later excised. Clinical studies (n=80) showed that mitral leaflet area increased
      by >30% in patients with inferior myocardial infarction and dilated
      cardiomyopathy versus normal; greater adaptation independently predicted less
      mitral regurgitation. This study explored whether mitral valve area changes over
      time within the same heart with ischemic mitral regurgitation. METHODS AND
      RESULTS: Twelve sheep were studied at baseline and 3 months after inferior
      myocardial infarction by 3D echocardiography; 6 were untreated and 6 were treated
      initially with an epicardial patch to limit left ventricular dilation and mitral
      regurgitation. Untreated sheep developed left ventricular dilation at 3 months,
      with global dysfunction (mean+/-SD ejection fraction, 24+/-10% versus 44+/-10%
      with patching, P=0.02) and moderate mitral regurgitation (vena contracta, 5.0+/
      1.0 versus 0.8+/-1.0 mm, P<0.0002). In untreated sheep, total diastolic leaflet
      area increased from 13.1+/-1.3 to 18.1+/-2.5 cm(2) (P=0.0001). In patched sheep,
      leaflet area at 3 months was not significantly different from baseline sheep
      values (13.0+/-1.1 versus baseline, 12.1+/-1.8 cm(2), P=0.31). CONCLUSIONS:
      Mitral valve area, independent of systolic stretch, increases over time as the
      left ventricular remodels after inferior myocardial infarction. This increase,
      however, fails to compensate adequately for tethering to prevent mitral
      regurgitation. Understanding the mechanism of valve adaptation can potentially
      suggest new biological and surgical therapeutic targets.

PMID- 19752394
TI  - The therapeutic effect of bone marrow-derived liver cells in the phenotypic
      correction of murine hemophilia A.
AB  - The transdifferentiation of bone marrow cells (BMCs) into hepatocytes has created
      enormous interest in applying this process to the development of cellular
      medicine for degenerative and genetic diseases. Because the liver is the primary
      site of factor VIII (FVIII) synthesis, we hypothesized that the partial
      replacement of mutated liver cells by healthy cells in hemophilia A mice could
      manage the severity of the bleeding disorder. We perturbed the host liver with
      acetaminophen to facilitate the engraftment and hepatic differentiation of
      lineage-depleted enhanced green fluorescent protein-expressing BMCs.
      Immunohistochemistry experiments with the liver tissue showed that the donor
      derived cells expressed the markers of both hepatocytes (albumin and cytokeratin
      18) and endothelial cells (von Willebrand factor). The results of fluorescent in
      situ hybridization and immunocytochemistry experiments suggested that
      differentiation was direct in this model. The BMC-recipient mice expressed FVIII
      protein and survived in a tail clip challenge experiment. Furthermore, a
      coagulation assay confirmed that the plasma FVIII activity was maintained at
      20.4% (+/- 3.6%) of normal pooled plasma activity for more than a year without
      forming its inhibitor. Overall, this report demonstrated that BMCs rescued the
      bleeding phenotype in hemophilia A mice, suggesting a potential therapy for this
      and other related disorders.

PMID- 19752395
TI  - Undifferentiated hematopoietic cells are characterized by a genome-wide
      undermethylation dip around the transcription start site and a hierarchical
      epigenetic plasticity.
AB  - Evidence for the epigenetic regulation of hematopoietic stem cells (HSCs) is
      growing, but the genome-wide epigenetic signature of HSCs and its functional
      significance remain unclear. In this study, from a genome-wide comparison of CpG
      methylation in human CD34(+) and CD34(-) cells, we identified a characteristic
      undermethylation dip around the transcription start site of promoters and an
      overmethylation of flanking regions in undifferentiated CD34(+) cells. This
      "bivalent-like" CpG methylation pattern around the transcription start site was
      more prominent in genes not associated with CpG islands (CGI(-)) than CGI(+)
      genes. Undifferentiated hematopoietic cells also exhibited dynamic chromatin
      associated with active transcription and a higher turnover of histone acetylation
      than terminally differentiated cells. Interestingly, inhibition of chromatin
      condensation by chemical treatment (5-azacytidine, trichostatin A) enhanced the
      self-renewal of "stimulated" HSCs in reconstituting bone marrows but not "steady
      state" HSCs in stationary phase bone marrows. In contrast, similar treatments on
      more mature cells caused partial phenotypic dedifferentiation and apoptosis at
      levels correlated with their hematopoietic differentiation. Taken together, our
      study reveals that the undifferentiated state of hematopoietic cells is
      characterized by a unique epigenetic signature, which includes dynamic chromatin
      structures and an epigenetic plasticity that correlates to level of
      undifferentiation.

PMID- 19752396
TI  - The small Rho GTPase Cdc42 regulates neutrophil polarity via CD11b integrin
      signaling.
AB  - Neutrophil migration to sites of infection is the first line of cellular defense.
      A key event of migration is the maintenance of a polarized morphology, which is
      characterized by a single leading edge of filamentous actin and a contractile
      uropod devoid of filamentous actin protrusions. Using a mouse model of high Cdc42
      activity, we previously demonstrated the importance of Cdc42 activity in
      neutrophil migration. However, the specific functions of Cdc42 in this process
      remain to be understood. Using neutrophils genetically deficient in Cdc42, we
      show that Cdc42 regulates directed migration by maintaining neutrophil polarity.
      Although it is known to be activated at the front, Cdc42 suppresses protrusions
      at the uropod. Interestingly, Cdc42 makes use of the integrin CD11b during this
      process. Cdc42 determines the redistribution of CD11b at the uropod. In turn,
      using CD11b-null cells and CD11b crosslinking experiments, we show that CD11b
      modulates myosin light chain phosphorylation to suppress lateral protrusions. Our
      results uncover a new mechanism in which Cdc42 regulates the uropod through CD11b
      signaling to maintain polarity in migrating neutrophils. It also reveals new
      functions for CD11b in neutrophil polarity.

PMID- 19752397
TI  - The fatty acid desaturase 3 gene encodes for different FADS3 protein isoforms in
      mammalian tissues.
AB  - In 2000, Marquardt et al. (A. Marquardt, H. Stohr, K. White, and B. H. F. Weber.
      2000. cDNA cloning, genomic structure, and chromosomal localization of three
      members of the human fatty acid desaturase family. Genomics. 66: 176-183.)
      described the genomic structure of the fatty acid desaturase (FADS) cluster in
      humans. This cluster includes the FADS1 and FADS2 genes encoding, respectively,
      for the Delta 5- and Delta 6-desaturases involved in polyunsaturated fatty acid
      biosynthesis. A third gene, named FADS3, has recently been identified but no
      functional role has yet been attributed to the putative FADS3 protein. In this
      study, we investigated the FADS3 occurrence in rat tissues by using two specific
      polyclonal antibodies directed against the N-terminal and C-terminal ends of rat
      FADS3. Our results showed three potential protein isoforms of FADS3 (75 kDa, 51
      kDa, and 37 kDa) present in a tissue-dependent manner. The occurrence of these
      FADS3 isoforms did not depend on the mRNA level determined by real-time PCR. In
      parallel, mouse tissues were also tested and showed the same three FADS3 isoforms
      but with a different tissue distribution. Finally, we reported the existence of
      FADS3 in human cells and tissues but different new isoforms were identified. To
      conclude, we showed in this study that FADS3 does exist under multiple protein
      isoforms depending on the mammalian tissues. These results will help further
      investigations to determine the physiological function of FADS3.

PMID- 19752398
TI  - Genetic variation at the NPC1L1 gene locus, plasma lipoproteins, and heart
      disease risk in the elderly.
AB  - Niemann-Pick C1-like 1 protein (NPC1L1) plays a critical role in intestinal
      cholesterol absorption. Our objective was to examine whether five variants (
      133A>G, -18A>C, L272L, V1296V, and U3_28650A>G) at the NPC1L1 gene have effects
      on lipid levels, prevalence, and incidence of coronary heart disease (CHD) and
      lipid-lowering response to pravastatin. We studied 5,804 elderly participants
      from the PROSPER study, who were randomized to prava-statin 40 mg/day or placebo
      and were followed on average for 3.2 years. In the adjusted gender-pooled
      analyses, homozygous carriers of the minor alleles at four NPC1L1 sites (-18A>C,
      L272L, V1296V, and U3_28650A>G, minor allele frequencies 0.15-0.33) had 2-8%
      higher LDL-cholesterol (LDL-C) levels at baseline than homozygous carriers of the
      common alleles (P < 0.05). Homozygotes for the rare alleles also had a
      significant increase in the risk of CHD events on trial (range of hazard ratios
      1.50-1.67; P < 0.02), regardless of the treatment regimen. The -133 A>G
      polymorphism and not other variants was associated with 6 month LDL-C lowering (P
      = 0.02). Our data indicate that variation in the NPC1L1 gene is associated with
      plasma total and LDL-C levels and CHD risk.

PMID- 19752399
TI  - Identification and absolute configuration of dihydroxy-arachidonic acids formed
      by oxygenation of 5S-HETE by native and aspirin-acetylated COX-2.
AB  - Biosynthesis of the prostaglandin endoperoxide by the cyclooxygenase (COX)
      enzymes is accompanied by formation of a small amount of 11R
      hydroxyeicosatetraenoic acid (HETE), 15R-HETE, and 15S-HETE as by-products.
      Acetylation of COX-2 by aspirin abrogates prostaglandin synthesis and triggers
      formation of 15R-HETE as the sole product of oxygenation of arachidonic acid.
      Here, we investigated the formation of by-products of the transformation of 5S
      HETE by native COX-2 and by aspirin-acetylated COX-2 using HPLC-ultraviolet, GC
      MS, and LC-MS analysis. 5S,15S- dihydroxy (di)HETE, 5S,15R-diHETE, and 5S,11R
      diHETE were identified as by-products of native COX-2, in addition to the
      previously described di-endoperoxide (5S,15S-dihydroxy-9S,11R,8S,12S-diperoxy
      6E,13E-eicosadienoic acid) as the major oxygenation product. 5S,15R-diHETE was
      the only product formed by aspirin-acetylated COX-2. Both 5,15-diHETE and 5,11
      diHETE were detected in CT26 mouse colon carcinoma cells as well as in
      lipopolysaccharide-activated RAW264.7 cells incubated with 5S-HETE, and their
      formation was attenuated in the presence of the COX-2 specific inhibitor, NS-398.
      Aspirin-treated CT26 cells gave 5,15-diHETE as the most prominent product formed
      from 5S-HETE. 5S,15S-diHETE has been described as a product of the cross-over of
      5-lipoxygenase (5-LOX) and 15-LOX activities in elicited rat mononuclear cells
      and human leukocytes, and our studies implicate cross-over of the 5-LOX and COX-2
      pathways as an additional biosynthetic route.

PMID- 19752400
TI  - Polyclonality of BRAF mutations in acquired melanocytic nevi.
AB  - Melanocytic nevi are thought to be senescent clones of melanocytes that have
      acquired an oncogenic BRAF mutation. BRAF mutation is considered to be a crucial
      step in the initiation of melanocyte transformation. However, using
      immunomagnetic separation or laser-capture microdissection, we examined BRAF
      mutations in sets of approximately 50 single cells isolated from acquired
      melanocytic nevi from 13 patients and found a substantial number of nevus cells
      that contained wild-type BRAF mixed with nevus cells that contained BRAF(V600E).
      Furthermore, we simultaneously amplified BRAF exon 15 and a neighboring single
      nucleotide polymorphism (SNP), rs7801086, from nevus cell samples obtained from
      four patients who were heterozygous for this SNP. Subcloning and sequencing of
      the polymerase chain reaction products showed that both SNP alleles harbored the
      BRAF(V600E) mutation, indicating that the same BRAF(V600E) mutation originated
      from different cells. The polyclonality of BRAF mutations in acquired melanocytic
      nevi suggests that mutation of BRAF may not be an initial event in melanocyte
      transformation.

PMID- 19752401
TI  - Is what is good for the gander really good for the goose?

PMID- 19752402
TI  - Guideline-recommended antibiotics in community-acquired pneumonia: not perfect,
      but good.

PMID- 19752403
TI  - An empirical model to estimate the potential impact of medication safety alerts
      on patient safety, health care utilization, and cost in ambulatory care.
AB  - BACKGROUND: Because ambulatory care clinicians override as many as 91% of drug
      interaction alerts, the potential benefit of electronic prescribing (e
      prescribing) with decision support is uncertain. METHODS: We studied 279 476
      alerted prescriptions written by 2321 Massachusetts ambulatory care clinicians
      using a single commercial e-prescribing system from January 1 through June 30,
      2006. An expert panel reviewed a sample of common drug interaction alerts,
      estimating the likelihood and severity of adverse drug events (ADEs) associated
      with each alert, the likely injury to the patient, and the health care
      utilization required to address each ADE. We estimated the cost savings due to e
      prescribing by using third-party-payer and publicly available information.
      RESULTS: Based on the expert panel's estimates, electronic drug alerts likely
      prevented 402 (interquartile range [IQR], 133-846) ADEs in 2006, including 49 (14
      130) potentially serious, 125 (34-307) significant, and 228 (85-409) minor ADEs.
      Accepted alerts may have prevented a death in 3 (IQR, 2-13) cases, permanent
      disability in 14 (3-18), and temporary disability in 31 (10-97). Alerts
      potentially resulted in 39 (IQR, 14-100) fewer hospitalizations, 34 (6-74) fewer
      emergency department visits, and 267 (105-541) fewer office visits, for a cost
      savings of 402,619 USD (IQR, 141,012-1,012,386 USD). Based on the panel's
      estimates, 331 alerts were required to prevent 1 ADE, and a few alerts (10%)
      likely accounted for 60% of ADEs and 78% of cost savings. CONCLUSIONS: Electronic
      prescribing alerts in ambulatory care may prevent a substantial number of
      injuries and reduce health care costs in Massachusetts. Because a few alerts
      account for most of the benefit, e-prescribing systems should suppress low-value
      alerts.

PMID- 19752404
TI  - Health information technology as a tool, not an end: comment on "An empirical
      model to estimate the potential impact of medication safety alerts on patient
      safety, health care utilization, and cost in ambulatory care".

PMID- 19752405
TI  - Physical activity, function, and longevity among the very old.
AB  - BACKGROUND: Recommendations encouraging physical activity (PA) set no upper age
      limit, yet evidence supporting the benefits of PA among the very old is sparse.
      We examined the effects of continuing, increasing, or decreasing PA levels on
      survival, function, and health status among the very old. METHODS: Mortality data
      from ages 70 to 88 years and health, comorbidity, and functional status at ages
      70, 78, and 85 years were assessed through the Jerusalem Longitudinal Cohort
      Study (1990-2008). A representative sample of 1861 people born in 1920 and 1921
      enrolled in this prospective study, resulting in 17 109 person-years of follow-up
      for all-cause mortality. RESULTS: Among physically active vs sedentary
      participants, respectively, at age 70, the 8-year mortality was 15.2% vs 27.2% (P
      < .001); at age 78, the 8-year mortality was 26.1% vs 40.8% (P <.001); and at age
      85 years, the 3-year mortality was 6.8% vs 24.4% (P < .001). In Cox proportional
      hazards models adjusting for mortality risk factors, lower mortality was
      associated with PA level at ages 70 (hazard ratio, 0.61; 95% confidence interval,
      0.38-0.96), 78 (0.69; 0.48-0.98), and 85 (0.42; 0.25-0.68). A significant
      survival benefit was associated with initiating PA between ages 70 and 78 years
      (P = .04) and ages 78 and 85 years (P < .001). Participation in higher levels of
      PA, compared with being sedentary, did not show a dose-dependent association with
      mortality. The PA level at age 78 was associated with remaining independent while
      performing activities of daily living at age 85 (odds ratio, 1.92; 95% confidence
      interval, 1.11-3.33). CONCLUSIONS: Among the very old, not only continuing but
      also initiating PA was associated with better survival and function. This finding
      supports the encouragement of PA into advanced old age.

PMID- 19752406
TI  - Population-based intervention to reduce prehospital delays in patients with
      cerebrovascular events.
AB  - BACKGROUND: In patients with acute stroke, systemic thrombolysis needs to be
      administered within 3 hours of symptom onset. The aim of the present study was to
      reduce prehospital delays in a population-based intervention. METHODS: We
      performed a cluster-randomized trial with 48 zip code areas as cluster units in
      the catchment area of 3 inner-city hospitals in Berlin, Germany. The primary end
      point was time between symptom onset and hospital admission. The intervention
      consisted of an educational letter indicating stroke symptoms and emphasizing the
      importance of calling the emergency medical services. We additionally included a
      bookmark and sticker with the emergency medical services' telephone number. We
      fitted a series of log-normal survival regression models (time to admission) with
      frailty terms shared by inhabitants of the same zip code area. RESULTS: A total
      of 75 720 inhabitants received the intervention. Between 2004 and 2005, 741
      patients with cerebrovascular events were admitted from the control areas (n =
      24) and 647 from the intervention areas (n = 24). A prehospital time of 2 hours
      or less and 3 hours or less was achieved by 22% and 28% of patients,
      respectively, in the control group compared with 26% and 34%, respectively, in
      the intervention group. In the log-normal model, time to hospital was reduced by
      27% in the intervention group in women (acceleration factor, 0.73; 95% confidence
      interval, 0.58-0.94), while no significant effect was found in men. CONCLUSIONS:
      The population-based intervention was effective in reducing prehospital delays in
      women but not in men. Future research should focus on the potential
      transferability of the intervention, its sustainability, and sex-specific impact.

PMID- 19752407
TI  - The prevalence of weekly angina among patients with chronic stable angina in
      primary care practices: The Coronary Artery Disease in General Practice (CADENCE)
      Study.
AB  - BACKGROUND: Angina, the cardinal symptom of coronary artery disease (CAD), is
      amenable to a range of therapies, and its routine assessment is considered a
      performance measure of quality. However, the prevalence of frequent angina among
      outpatients with CAD is unknown. METHODS: The Coronary Artery Disease in General
      Practice (CADENCE) Study utilized a cluster-stratified, cross-sectional design to
      examine angina frequency in patients with stable angina attending Australian
      primary care practices. The 207 participating primary care practitioners
      recruited 2031 consecutive patients, irrespective of the purpose of their visit.
      Angina frequency was quantified with the Seattle Angina Questionnaire (SAQ), and
      weekly angina was defined as having 1 or more episodes per week over the
      preceding 4 weeks [hereinafter, "weekly (> or =1) angina"]. RESULTS: Among
      primary care practice patients with stable angina, 29% (95% confidence interval
      [CI], 26%-31%) experienced weekly (> or =1) angina, which was associated with
      greater physical limitations and worse quality of life (24% and 27% lower SAQ
      scores, respectively; P < .05) compared with those with minimal angina (angina
      less than once a week over the preceding 4 weeks). The proportion of patients
      with weekly (> or =1) angina within a clinic ranged from none (14% of clinics) to
      more than 50% (18% of clinics). Patient characteristics associated with weekly (>
      or =1) angina included female sex (odds ratio [OR], 1.42; 95% CI, 1.13-1.78), a
      history of heart failure (OR, 1.59; 95% CI, 1.22-2.08), and peripheral artery
      disease (OR 1.89; 95% CI, 1.42-2.51; P < .001 for all comparisons). CONCLUSIONS:
      Almost 1 in 3 patients with stable angina attending primary care practices had
      angina at least once a week, which was associated with worse quality of life.
      Moreover, weekly (> or =1) angina varied considerably across clinics, possibly
      reflecting variability in the identification and management of angina. The
      potential role of an angina performance measure to improve patients' outcomes,
      including symptom control, warrants further consideration.

PMID- 19752408
TI  - Effectiveness of implantable cardioverter-defibrillators for the primary
      prevention of sudden cardiac death in women with advanced heart failure: a meta
      analysis of randomized controlled trials.
AB  - BACKGROUND: Numerous clinical trials have established a role for implantable
      cardioverter-defibrillators in the prevention of sudden cardiac death in patients
      with heart failure. However, questions remain that regard the clinical benefit of
      these therapies in different patient subgroups. Specifically, the role of
      implantable cardioverter-defibrillators in women with heart failure for the
      primary prevention of sudden cardiac death has not been well established. Our
      objective is to determine whether implantable cardioverter-defibrillators reduce
      mortality in women with advanced heart failure. METHODS: We searched MEDLINE
      (1950-2008), EMBASE (1988-2008, week 24), the Cochrane Controlled Trials Register
      (third quarter, 2008), the National Institute of Health ClinicalTrials.gov
      database, the Food and Drug Administration Web site, and various reports
      presented at scientific meetings (1994-2007). Eligible studies were randomized
      controlled trials of implantable cardioverter/defibrillators for the primary
      prevention of sudden cardiac death in patients with heart failure that reported
      all-cause mortality as an outcome for the female population. Of the 2619 reports
      identified, 5 trials that enroll 934 women were included in the meta-analysis.
      RESULTS: Pooled data from the 5 trials revealed no statistically significant
      decrease in all-cause mortality in women with heart failure who receive
      implantable cardioverter-defibrillators (hazard ratio, 1.01; 95% confidence
      interval, 0.76-1.33). CONCLUSIONS: Implantable cardioverter-defibrillator therapy
      for the primary prevention of sudden cardiac death in women does not reduce all
      cause mortality. Further studies are needed to investigate the reasons for this
      ob servation and to define the population of women who may benefit most from
      implantable cardioverter-defibrillator therapy.

PMID- 19752409
TI  - Randomized controlled trial of proactive web-based alcohol screening and brief
      intervention for university students.
AB  - BACKGROUND: University students drink more heavily than their nonstudent peers
      and are often unaware that their drinking is risky and exceeds normative levels.
      We tested the efficacy of a proactive Web-based alcohol screening and brief
      intervention program. METHODS: A randomized controlled trial was conducted at an
      Australian university in 2007. Invitations were sent to 13 000 undergraduates
      (age range, 17-24 years) to complete a Web-based Alcohol Use Disorders
      Identification Test. Of 7237 students who responded, 2435 scored in the
      hazardous/harmful range (> or =8) and were randomized, and 2050 (84%) completed
      at least 1 follow-up assessment. Intervention was 10 minutes of Web-based
      motivational assessment and personalized feedback. Controls received only
      screening. Follow-up assessments were conducted at 1 and 6 months with observers
      and participants blinded to allocation. Outcome measures were drinking frequency,
      typical occasion quantity, overall volume, number of personal problems, an
      academic problems score, prevalence of binge drinking, and prevalence of heavy
      drinking. RESULTS: Mean (SD) baseline Alcohol Use Disorders Identification Test
      scores for control and intervention groups were 14.3 (5.1) and 14.2 (5.1),
      respectively. After 1 month, participants receiving intervention drank less often
      (rate ratio [RR], 0.89; 95% confidence interval [CI], 0.83-0.94), smaller
      quantities per occasion (RR, 0.93; 95% CI, 0.88-0.98), and less alcohol overall
      (RR, 0.83; 95% CI, 0.78-0.90) than did controls. Differences in alcohol-related
      harms were nonsignificant. At 6 months, intervention effects persisted for
      drinking frequency (RR, 0.91; 95% CI, 0.85-0.97) and overall volume (RR, 0.89;
      95% CI, 0.82-0.96) but not for other variables. CONCLUSION: Proactive Web-based
      screening and intervention reduces drinking in undergraduates, and such a program
      could be implemented widely.

PMID- 19752410
TI  - Improving outcomes in elderly patients with community-acquired pneumonia by
      adhering to national guidelines: Community-Acquired Pneumonia Organization
      International cohort study results.
AB  - BACKGROUND: To define whether elderly patients hospitalized with community
      acquired pneumonia (CAP) had better outcomes if they were treated with empirical
      antimicrobial therapy adherent to the 2007 Infectious Diseases Society of America
      (IDSA)/American Thoracic Society (ATS) guidelines for CAP. METHODS: This was a
      secondary analysis of the CAPO International Cohort Study database, which
      contained data from a total of 1725 patients aged 65 years or older who were
      hospitalized with CAP. Data from June 1, 2001, until January 1, 2007, were
      analyzed from 43 centers in 12 countries including North America (n = 2), South
      America (n = 4), Europe (n = 4), Africa (n = 1), and Southeast Asia (n = 1).
      Initial empirical therapy for CAP was evaluated for guideline compliance
      according to the 2007 IDSA/ATS guidelines for CAP. Time to clinical stability,
      length of stay (LOS), total in-hospital mortality, and CAP-related mortality for
      each group were calculated. Comparisons between groups were made using cumulative
      incidence curves and competing risks regression. RESULTS: Among the 1649 patients
      with CAP, aged 65 years or older, 975 patients were given antimicrobial regimens
      adherent to the IDSA/ATS for CAP guidelines, while 660 patients were treated with
      nonadherent regimens (465 patients were "undertreated"; 195 were "overtreated").
      Adherence to guidelines was associated with a statistically significant decreased
      time to achieve clinical stability compared with nonadherence: the proportion of
      patients who reached clinical stability by 7 days was 71% (95% confidence
      interval [CI], 68%-74%) and 57% (95% CI, 53%-61%) (P < .01), respectively.
      Guideline adherence was also associated with shorter LOS (median adherence LOS, 8
      days; interquartile range [IQR], 5-15 days; median nonadherence LOS, 10 days;
      IQR, 6-24 days) (P < .01) and decreased overall in-hospital mortality (8%; 95%
      CI, 7%-10% vs 17%; 95% CI, 14%-20%) (P < .01). CONCLUSION: Implementation of
      national guidelines at the local hospital level will improve not only mortality
      and LOS of elderly patients hospitalized with CAP but also time to clinical
      stability.

PMID- 19752411
TI  - Guideline-concordant therapy and reduced mortality and length of stay in adults
      with community-acquired pneumonia: playing by the rules.
AB  - BACKGROUND: Community-acquired pneumonia (CAP) is a major cause of morbidity and
      mortality worldwide. Clinical practice guidelines for empirical CAP treatment,
      formulated jointly by the Infectious Diseases Society of America (IDSA) and
      American Thoracic Society (ATS), remain controversial and inconsistently applied.
      We evaluated the impact of guideline-concordant therapy on in-hospital survival
      and other outcomes using a large database including adults treated for CAP in
      both community and tertiary care hospitals. METHODS: We evaluated the association
      between in-hospital survival and guideline-concordant therapy using logistic
      regression models. Time until discharge from hospital and discontinuation of
      parenteral therapy were evaluated using survival analysis. RESULTS: Of 54 619 non
      intensive care unit inpatients with CAP hospitalized at 113 community hospitals
      and tertiary care centers, 35 477 (65%) received initial guideline-concordant
      therapy. After adjustment for severity of illness and other confounders,
      guideline-concordant therapy was associated with decreased in-hospital mortality
      (odds ratio [OR], 0.70; 95% confidence interval [CI], 0.63-0.77), sepsis (OR,
      0.83; 95% CI, 0.72-0.96), and renal failure (OR, 0.79; 95% CI, 0.67-0.94), and
      reduced both length of stay and duration of parenteral therapy by approximately
      0.6 days (P < .001 for both comparisons). These findings were robust with
      alternate definitions of "concordance" and were linked to treatment with
      fluoroquinolone or macrolide agents. CONCLUSIONS: Guideline-concordant therapy
      for CAP is associated with improved health outcomes and diminished resource use
      in adults. The mechanisms underlying this finding remain speculative and warrant
      further study, but our findings nonetheless support compliance with CAP clinical
      practice guidelines as a benchmark of quality of care.

PMID- 19752412
TI  - Confounding of subgroup analyses in randomized data.

PMID- 19752413
TI  - Yes we can? Can all Americans join the imminent electronic health care
      revolution? A survey of patients receiving care at a public hospital.

PMID- 19752414
TI  - Vitamin D supplements vs plasma level.

PMID- 19752415
TI  - Meat intake and mortality: evidence for harm, no effect, or benefit?

PMID- 19752416
TI  - Higher red meat intake may be a marker of risk, not a risk factor itself.

PMID- 19752417
TI  - Is red blood cell distribution width a marker of overall membrane integrity?

PMID- 19752418
TI  - Life prolonging in name only?

PMID- 19752421
TI  - Glaucoma with early visual field loss affecting both hemifields and the risk of
      disease progression.
AB  - OBJECTIVE: To evaluate whether damage to both hemifields in glaucomatous eyes
      predicts more rapid disease progression than does single-hemifield involvement.
      METHODS: We reviewed the medical records of 43 660 consecutive patients. Eyes
      with glaucomatous optic neuropathy, 10 or more Swedish Interactive Threshold
      Algorithm standard 24-2 visual fields in at least 5 years, and mean deviation
      (MD) smaller than -6.0 dB were included. Pointwise linear regression was used to
      determine progression. Cox proportional hazards analysis was used to calculate
      risk of progression based on different baseline covariates. RESULTS: We enrolled
      205 eyes (205 patients; mean [SD] age, 64.2 [11.0] years; follow-up, 6.5 [1.8]
      years; number of visual fields, 12.3 [2.9]). Patients were divided into 3 groups:
      initial superior defect (group A; n = 79; MD, -3.4 [1.9] dB), initial inferior
      defect (group B; n = 61; MD, -3.4 [1.8] dB), and both hemifields affected (group
      C; n = 65; MD, -4.2 [1.5] dB). Group C progressed faster than did groups A and B
      (P < .02). Multivariate analysis showed significant effect of higher baseline
      intraocular pressure, thinner central corneal thickness, and initial damage to
      both hemifields. CONCLUSIONS: Initial damage to both hemifields increases the
      risk of glaucoma progression. More aggressive therapy should be considered for
      these eyes.

PMID- 19752422
TI  - The African Descent and Glaucoma Evaluation Study (ADAGES): design and baseline
      data.
AB  - OBJECTIVE: To identify factors accounting for differences in glaucoma onset and
      rate of progression between individuals of African descent and European descent.
      DESIGN: A prospective, multicenter observational cohort study of 1221
      participants of African descent and European descent with no glaucoma (normal),
      suspected glaucoma, and glaucoma. Six hundred eighty-six patient participants in
      the African Descent and Glaucoma Evaluation Study will be followed up
      longitudinally. Four hundred thirty-six participants of European descent from the
      Diagnostic Innovations in Glaucoma Study (DIGS) were also included. Baseline
      demographics, visual function (standard automated perimetry, short-wavelength
      automated perimetry, frequency doubling technology perimetry), optic nerve
      structure (retina tomography, optical coherence tomography), clinical status, and
      risk factors were measured. RESULTS: Individuals of African descent had (1)
      thinner corneas (P < .001) across all diagnostic groups, (2) a higher percentage
      of reported diabetes mellitus (P < .001) and high blood pressure (P < .001) and a
      lower percentage of reported heart disease (P = .001), and (3) worse pattern
      standard deviation for standard automated perimetry fields overall (P = .001) and
      within normal limits (P = .01) than individuals of European descent. No
      differences were present for mean intraocular pressure (P = .79). CONCLUSIONS:
      Significant baseline differences were found in a number of clinical findings
      between persons of African descent compared with European descent. Longitudinal
      data from the African Descent and Glaucoma Evaluation Study will be important for
      determining which baseline features are important and predictive for accurate
      diagnosis and follow-up in this high-risk group. Trial Registration
      clinicaltrials.gov Identifier: NCT00221923.

PMID- 19752424
TI  - Development of criteria for evaluating clinical response in thyroid eye disease
      using a modified Delphi technique.
AB  - OBJECTIVE: To identify components of a provisional clinical response index for
      thyroid eye disease using a modified Delphi technique. METHODS: The International
      Thyroid Eye Disease Society conducted a structured, 3-round Delphi exercise
      establishing consensus for a core set of measures for clinical trials in thyroid
      eye disease. The steering committee discussed the results in a face-to-face
      meeting (nominal group technique) and evaluated each criterion with respect to
      its feasibility, reliability, redundancy, and validity. Redundant measures were
      consolidated or excluded. RESULTS: Criteria were parsed into 11 domains for the
      Delphi surveys. Eighty-four respondents participated in the Delphi 1 survey,
      providing 220 unique items. Ninety-two members (100% of the respondents from
      Delphi 1 plus 8 new participants) responded in Delphi 2 and rated the same 220
      items. Sixty-four members (76% of participants) rated 153 criteria in Delphi 3
      (67 criteria were excluded because of redundancy). Criteria with a mean greater
      than 6 (1 = least appropriate to 9 = most appropriate) were further evaluated by
      the nominal group technique and provisional core measures were chosen.
      CONCLUSIONS: Using a Delphi exercise, we developed provisional core measures for
      assessing disease activity and severity in clinical trials of therapies for
      thyroid eye disease. These measures will be iteratively refined for use in
      multicenter clinical trials.

PMID- 19752425
TI  - Experimental ocular tuberculosis in guinea pigs.
AB  - OBJECTIVE: To develop an animal model of intraocular tuberculosis (TB) with
      features of pulmonary TB and extrapulmonary dissemination to the eye. METHODS:
      Hartley strain guinea pigs were infected via an aerosol route with virulent
      Mycobacterium tuberculosis. One group of guinea pigs was infected with a
      relatively low bacterial inoculum and received no treatment. A second group of
      guinea pigs received high-dose infection and were treated with the first-line
      anti-TB drugs isoniazid, rifampin, and pyrazinamide. Development of ocular TB
      lesions was documented by histological analysis, acid-fast staining, and real
      time polymerase chain reaction for M tuberculosis DNA. RESULTS: Untreated guinea
      pigs developed pulmonary and extrapulmonary TB. Ocular TB, primarily involving
      the uvea, developed in 5 of 12 eyes (42%). Uveal granulomatous lesions showed the
      presence of acid-fast organisms and M tuberculosis DNA. In treated animals, none
      of the 8 eyes examined revealed the presence of acid-fast organisms; however,
      there was mild nongranulomatous uveitis in 4 eyes. CONCLUSIONS: Mycobacterium
      tuberculosis delivered via aerosol to guinea pigs results in extrapulmonary
      dissemination to the eye. Of significance, intraocular changes in this model
      include granulomatous inflammation and the presence of acid-fast organisms, as
      seen in human cases of ocular TB. Clinical Relevance The guinea pig model may
      provide greater insight into the pathogenesis of intraocular TB and assist in the
      development of novel modalities to treat this global infectious disease.

PMID- 19752428
TI  - Dr Thompson's eye water.

PMID- 19752427
TI  - The relation of markers of inflammation and endothelial dysfunction to the
      prevalence and progression of diabetic retinopathy: Wisconsin epidemiologic study
      of diabetic retinopathy.
AB  - OBJECTIVE: To determine the relation of glycemia, blood pressure, and serum total
      cholesterol level as systemic markers of inflammation and endothelial dysfunction
      to the prevalence and incidence of diabetic retinal outcomes in persons with long
      duration type 1 diabetes mellitus. METHODS: Longitudinal population-based study
      of persons with type 1 diabetes mellitus who received care for their diabetes in
      south central Wisconsin from July 1, 1979, to June 30, 1980. Data for this
      investigation were obtained from the 1990-1992 through the 2005-2007 follow-up
      examinations. Main outcome measures included the severity of diabetic retinopathy
      (DR) and macular edema (ME). RESULTS: In the 1990-1992 prevalence data, soluble
      vascular cell adhesion molecule, tumor necrosis factor, and homocysteine levels
      were associated with increased odds of more severe DR (odds ratios [highest vs
      lowest quartile], 3.95 [95% confidence interval, 1.66-9.39], 5.46 [2.38-12.52],
      and 7.46 [2.91-19.16], respectively) in those with kidney disease while
      controlling for relevant confounders. Similar odds were found for proliferative
      DR. Only total homocysteine level was associated with increased odds of ME (3.80
      [95% confidence interval, 1.91-7.54]), irrespective of kidney disease. None of
      the markers were associated with incidence of proliferative DR, ME, or
      progression of DR 15 years later. CONCLUSIONS: A limited number of markers are
      associated with increased odds of prevalent retinal outcomes in persons with type
      1 diabetes mellitus and kidney disease. Only homocysteine level is associated
      with ME in those with and without kidney disease. In the absence of kidney
      disease, the markers do not add to the more conventional descriptors and
      predictors of DR in persons with type 1 diabetes mellitus. This may reflect the
      close association of DR and kidney disease in diabetic persons.

PMID- 19752423
TI  - Description of the Age-Related Eye Disease Study 9-step severity scale applied to
      participants in the Complications of Age-related Macular Degeneration Prevention
      Trial.
AB  - OBJECTIVE: To describe characteristics of the Age-Related Eye Disease Study
      (AREDS) 9-step severity scale applied to participants in the Complications of Age
      related Macular Degeneration Prevention Trial (CAPT). METHODS: Eligibility
      criteria for CAPT required 10 or more large (>or=125 microm) drusen in each eye.
      Readers graded baseline photographs from all participants and all follow-up
      photographs from 402 untreated eyes. Drusen and pigment characteristics were used
      to assign the AREDS scale score. Choroidal neovascularization was identified from
      fluorescein angiograms. Geographic atrophy involving the macular center was
      identified from color photographs. RESULTS: Among 1001 untreated eyes, 90% were
      at steps 5 to 7 at baseline. The 5-year incidence of advanced age-related macular
      degeneration (AMD) increased with each step from 8% (step 4) to 40% (steps 8 and
      9 combined). These rates were similar to those reported in AREDS. Among 261 eyes
      with all 5 annual photograph gradings available and without progression to
      advanced AMD, 55% of eyes had scores that indicated improvement at least once.
      Before progression to advanced AMD, only 32% of 141 eyes either went through step
      8 or 9 or had an increase of 2 or more steps from baseline. CONCLUSIONS: The
      AREDS 9-step severity scale was predictive of development of advanced AMD. The
      AREDS scale has deficiencies as a surrogate outcome for progression to advanced
      AMD.

PMID- 19752429
TI  - Use of Global Visual Acuity Data in a time trade-off approach to calculate the
      cost utility of cataract surgery.
AB  - OBJECTIVE: To determine the cost utility of cataract surgery worldwide using
      visual acuity (VA) outcomes and utility values determined by the time trade-off
      (TTO) method. DATA SOURCES: Some cost data were taken from a previous search
      conducted for 1995 to 2006 and we searched MEDLINE and Scopus and Google for more
      recent data (2006 and 2007). STUDY SELECTION: Articles were identified from the
      literature using "cataract surgery" in combination with the terms outcome or
      visual acuity. Additional searches were conducted using individual countries as a
      term in combination with VA, outcome, or cost. Regression curves were constructed
      from utility values derived from a TTO study and VA data. Gains in quality
      adjusted life-years (QALYs) were calculated based on life expectancy tables from
      the World Health Organization and discounts of 3% for both cost and benefit.
      Sensitivity analyses explored the effect of changes in discounting, life
      expectancy, preoperative VA, and cost. DATA EXTRACTION: If the data were usable,
      they were kept; otherwise they were discarded. DATA SYNTHESIS: Preoperative VA
      (logMAR) correlated with increasing gross national income per capita (Pearson
      correlation coefficient, -0.784; P < .001) and showed that in developing
      countries preoperative vision is much poorer compared with developed countries.
      Cost utility data ranged from $3.5 to $834/QALY in developing countries to $159
      to $1356/QALY in developed countries. Sensitivity analysis showed that changing
      life expectancy, VA, and discount rate resulted in moderate changes. CONCLUSIONS:
      The TTO approach demonstrates that cataract surgery is extremely cost-effective.

PMID- 19752426
TI  - Change in area of geographic atrophy in the Age-Related Eye Disease Study: AREDS
      report number 26.
AB  - OBJECTIVE: To characterize progression of geographic atrophy (GA) associated with
      age-related macular degeneration in AREDS as measured by digitized fundus
      photographs. METHODS: Fundus photographs from 181 of 4757 AREDS participants with
      a GA area of at least 0.5 disc areas at baseline or from participants who
      developed bilateral GA during follow-up were scanned, digitized, and evaluated
      longitudinally. Geographic atrophy area was determined using planimetry. Rates of
      progression from noncentral to central GA and of vision loss following
      development of central GA included the entire AREDS cohort. RESULTS: Median
      initial lesion size was 4.3 mm(2). Average change in digital area of GA from
      baseline was 2.03 mm(2) (standard error of the mean, 0.24 mm(2)) at 1 year, 3.78
      mm(2) (0.24 mm(2)) at 2 years, 5.93 mm(2) (0.34 mm(2)) at 3 years, and 1.78 mm(2)
      (0.086 mm(2)) per year overall. Median time to developing central GA after any GA
      diagnosis was 2.5 years (95% confidence interval, 2.0-3.0). Average visual acuity
      decreased by 3.7 letters at first documentation of central GA, and by 22 letters
      at year 5. CONCLUSIONS: Growth of GA area can be reliably measured using standard
      fundus photographs that are digitized and subsequently graded at a reading
      center. Development of GA is associated with subsequent further growth of GA,
      development of central GA, and loss in central vision.

PMID- 19752430
TI  - A perspective on commercial relationships between ophthalmology and industry.
AB  - Relationships between physicians and industry including pharmaceutical companies
      and device manufacturers are being closely scrutinized by the public and the
      media. These companies can contribute beneficially to patient outcomes by
      supporting research that improves eye care. However, ethical issues may arise
      that affect practicing ophthalmologists, researchers, academic faculty, and
      ophthalmologic organizations. These topics were discussed at a symposium
      sponsored by the American Ophthalmological Society in May 2008. After this
      meeting, the council of the society developed this perspective to clarify some of
      the issues at the interface of industry and ophthalmology. The perspective is
      intended to provide some guidance to physicians, researchers, and professional
      societies and to enhance further dialogue.

PMID- 19752432
TI  - Use of Global Visual Acuity Data in a time trade-off approach to calculate the
      cost utility of cataract surgery: methodological issues of cost-utility
      comparisons.

PMID- 19752431
TI  - SCOREing in retinal venous occlusive disease.

PMID- 19752433
TI  - Proposed mandate for instructions and labeling regarding the use of eye drops.

PMID- 19752434
TI  - Effect of digital problem-based learning cases on student learning outcomes in
      ophthalmology courses.
AB  - OBJECTIVE: To assess the impact of digital problem-based learning (PBL) cases on
      student learning in ophthalmology courses. METHODS: Ninety students were randomly
      divided into 3 classes (30 students per class). The first class studied under a
      didactic model. The other 2 classes were divided into 6 groups (10 students per
      group) and received PBL teaching; 3 groups studied via cases presented in digital
      form and the others studied via paper-form cases. The results of theoretical and
      case analysis examinations were analyzed using the chi(2) test. Student
      performance on the interval practice was analyzed using the Kruskal-Wallis test.
      Questionnaires were used to evaluate student and facilitator perceptions.
      RESULTS: Students in the digital groups exhibited better performance in the
      practice procedures according to tutorial evaluations compared with the other
      groups (P < .05). The 2 PBL classes had significantly higher mean results of
      theoretical and case analysis examinations (P < .001), but there was no
      significant difference between the 2 PBL classes. Ninety-three percent of
      students in the digital groups (vs 73% in the paper groups) noted that the cases
      greatly stimulated their interest. CONCLUSIONS: Introducing PBL into
      ophthalmology could improve educational quality and effectiveness. Digital PBL
      cases stimulate interest and motivate students to further improve diagnosis and
      problem-handling skills.

PMID- 19752435
TI  - Some flowers in ophthalmology.

PMID- 19752436
TI  - Management of fluocinolone implant dissociation during implant exchange.
AB  - Three patients with chronic, noninfectious uveitis requiring immunosuppressive
      therapy underwent fluocinolone acetonide (FA) implant exchange complicated by
      dissociation of the medication reservoir from its anchoring strut. In 2 patients,
      the medication reservoir descended into the vitreous cavity and required pars
      plana vitrectomy with intraocular foreign body removal techniques for its
      retrieval. The use of viscoelastic or perfluorocarbon to elevate the device was
      helpful in the safe removal of the FA implant device. Surgeons performing FA
      implant exchange should be aware of this potential complication and anticipate
      the possible need for vitreoretinal instrumentation and personnel. Patients
      undergoing FA explantation or exchange should be counseled regarding this
      potential complication prior to surgery.

PMID- 19752437
TI  - Retrograde metastasis of cutaneous melanoma to conjunctival lymphatics.

PMID- 19752438
TI  - Age-related hyperplasia of the nonpigmented ciliary body epithelium (Fuchs
      adenoma) simulating a ciliary body malignant neoplasm.

PMID- 19752439
TI  - Contrast sensitivity following amblyopia treatment in children.

PMID- 19752419
TI  - A randomized trial comparing the efficacy and safety of intravitreal
      triamcinolone with observation to treat vision loss associated with macular edema
      secondary to central retinal vein occlusion: the Standard Care vs Corticosteroid
      for Retinal Vein Occlusion (SCORE) study report 5.
AB  - OBJECTIVE: To compare the efficacy and safety of 1-mg and 4-mg doses of
      preservative-free intravitreal triamcinolone with observation for eyes with
      vision loss associated with macular edema secondary to perfused central retinal
      vein occlusion (CRVO). METHODS: Multicenter, randomized, clinical trial of 271
      participants. MAIN OUTCOME MEASURE: Gain in visual acuity letter score of 15 or
      more from baseline to month 12. RESULTS: Seven percent, 27%, and 26% of
      participants achieved the primary outcome in the observation, 1-mg, and 4-mg
      groups, respectively. The odds of achieving the primary outcome were 5.0 times
      greater in the 1-mg group than the observation group (odds ratio [OR], 5.0; 95%
      confidence interval [CI], 1.8-14.1; P = .001) and 5.0 times greater in 4-mg group
      than the observation group (OR, 5.0; 95% CI, 1.8-14.4; P = .001); there was no
      difference identified between the 1-mg and 4-mg groups (OR, 1.0; 95% CI, 0.5-2.1;
      P = .97). The rates of elevated intraocular pressure and cataract were similar
      for the observation and 1-mg groups, but higher in the 4-mg group. CONCLUSIONS:
      Intravitreal triamcinolone is superior to observation for treating vision loss
      associated with macular edema secondary to CRVO in patients who have
      characteristics similar to those in the SCORE-CRVO trial. The 1-mg dose has a
      safety profile superior to that of the 4-mg dose. Application to Clinical
      Practice Intravitreal triamcinolone in a 1-mg dose, following the retreatment
      criteria applied in the SCORE Study, should be considered for up to 1 year, and
      possibly 2 years, for patients with characteristics similar to those in the SCORE
      CRVO trial. Trial Registration clinicaltrials.gov Identifier: NCT00105027.

PMID- 19752440
TI  - Evisceration after complete evaluation an acceptable option.

PMID- 19752420
TI  - A randomized trial comparing the efficacy and safety of intravitreal
      triamcinolone with standard care to treat vision loss associated with macular
      Edema secondary to branch retinal vein occlusion: the Standard Care vs
      Corticosteroid for Retinal Vein Occlusion (SCORE) study report 6.
AB  - OBJECTIVE: To compare the efficacy and safety of 1-mg and 4-mg doses of
      preservative-free intravitreal triamcinolone with standard care (grid
      photocoagulation in eyes without dense macular hemorrhage and deferral of
      photocoagulation until hemorrhage clears in eyes with dense macular hemorrhage)
      for eyes with vision loss associated with macular edema secondary to branch
      retinal vein occlusion (BRVO). METHODS: Multicenter, randomized clinical trial of
      411 participants. Main Outcome Measure Gain in visual acuity letter score of 15
      or more from baseline to month 12. RESULTS: Twenty-nine percent, 26%, and 27% of
      participants achieved the primary outcome in the standard care, 1-mg, and 4-mg
      groups, respectively. None of the pairwise comparisons between the 3 groups was
      statistically significant at month 12. The rates of elevated intraocular pressure
      and cataract were similar for the standard care and 1-mg groups, but higher in
      the 4-mg group. CONCLUSIONS: There was no difference identified in visual acuity
      at 12 months for the standard care group compared with the triamcinolone groups;
      however, rates of adverse events (particularly elevated intraocular pressure and
      cataract) were highest in the 4-mg group. Application to Clinical Practice Grid
      photocoagulation as applied in the SCORE Study remains the standard care for
      patients with vision loss associated with macular edema secondary to BRVO who
      have characteristics similar to participants in the SCORE-BRVO trial. Grid
      photocoagulation should remain the benchmark against which other treatments are
      compared in clinical trials for eyes with vision loss associated with macular
      edema secondary to BRVO. Trial Registration clinicaltrials.gov Identifier:
      NCT00105027.

PMID- 19752442
TI  - Evisceration of blind, painful eyes with occult uveal melanoma not a crime.

PMID- 19752443
TI  - Response to editorial about the convergence insufficiency treatment trial.

PMID- 19752441
TI  - Blind eyes with occult malignant melanoma.

PMID- 19752446
TI  - The steroid controversy in bacterial keratitis.

PMID- 19752447
TI  - Child neurology: a case illustrating the role of imaging in evaluation of sudden
      infant death.

PMID- 19752449
TI  - Seizure frequency and lateralization affect progression of atrophy in temporal
      lobe epilepsy.
AB  - BACKGROUND: It is unclear which factors lead to progressive neuronal damage in
      mesial temporal lobe epilepsy (MTLE). The objective of this study was to evaluate
      whether progressive hippocampal and extrahippocampal atrophy occur in patients
      with MTLE and whether this atrophy is related to seizures. METHOD: We performed 2
      MRI scans in 33 patients with clinical and electroencephalographic diagnosis of
      MTLE and in 24 healthy controls. MRI was performed in a 2-T scanner, and a T1
      weighted gradient-echo sequence with 1 mm thickness was used for voxel-based
      morphometry analysis. Follow-up images were obtained at least 7 months after the
      first baseline MRI. Comparisons between the patient's follow-up and baseline
      MRIs, and between patients and controls, were performed. A corrected p value of
      0.05 was set as the threshold for the statistical analysis. RESULTS: Follow-up
      MRI was performed after a median interval of 39 months (range 7-85 months). Three
      patients were seizure-free between the first and second MRIs. We observed
      progressive white and gray matter atrophy (p < 0.05) in patients with MTLE. This
      progression was more intense in patients with left MTLE compared with right MTLE.
      A higher frequency of seizures and a longer duration of epilepsy were associated
      with progression of gray and white matter atrophy in patients with MTLE.
      CONCLUSION: The progression of white and gray matter atrophy in patients with
      mesial temporal lobe epilepsy (MTLE) was more intense in patients with left MTLE
      and was associated with poorer seizure control and a longer duration of epilepsy.

PMID- 19752450
TI  - Interrater reliability of EEG-video monitoring.
AB  - OBJECTIVE: The diagnosis of psychogenic nonepileptic seizures (PNES) can be
      challenging. In the absence of a gold standard to verify the reliability of the
      diagnosis by EEG-video, we sought to assess the interrater reliability of the
      diagnosis using EEG-video recordings. METHODS: Patient samples consisted of 22
      unselected consecutive patients who underwent EEG-video monitoring and had at
      least an episode recorded. Other test results and histories were not provided
      because the goal was to assess the reliability of the EEG-video. Data were sent
      to 22 reviewers, who were board-certified neurologists and practicing
      epileptologists at epilepsy centers. Choices were 1) PNES, 2) epilepsy, and 3)
      nonepileptic but not psychogenic ("physiologic") events. Interrater agreement was
      measured using a kappa coefficient for each diagnostic category. We used
      generalized kappa coefficients, which measure the overall level of between-method
      agreement beyond that which can be ascribed to chance. We also report category
      specific kappa values. RESULTS: For the diagnosis of PNES, there was moderate
      agreement (kappa = 0.57, 95% confidence interval [CI] 0.39-0.76). For the
      diagnosis of epilepsy, there was substantial agreement (kappa = 0.69, 95% CI 0.51
      0.86). For physiologic nonepileptic episodes, the agreement was low (kappa =
      0.09, 95% CI 0.02-0.27). The overall kappa statistic across all 3 diagnostic
      categories was moderate at 0.56 (95% CI 0.41-0.73). CONCLUSIONS: Interrater
      reliability for the diagnosis of psychogenic nonepileptic seizures by EEG-video
      monitoring was only moderate. Although this may be related to limitations of the
      study (diagnosis based on EEG-video alone, artificial nature of the forced choice
      paradigm, single episode), it highlights the difficulties and subjective
      components inherent to this diagnosis.

PMID- 19752451
TI  - Association of plasma amyloid beta with risk of dementia: the prospective Three
      City Study.
AB  - OBJECTIVE: Several lines of evidence indicate that a decrease in the CSF
      concentration of amyloid beta(42) (Abeta(42)) is a potential biomarker for
      incident Alzheimer disease. In contrast, studies on plasma Abeta(1-40) and
      Abeta(1-42) peptide levels have yielded contradictory results. Here, we explored
      the links between incident dementia and plasma Abeta(1-40) and Abeta(1-42)
      peptide concentrations in the prospective, population-based Three-City (3C)
      Study. We also assessed the association between plasma concentrations of
      truncated Abeta (Abeta(n-40) and Abeta(n-42)) and the risk of dementia. METHODS:
      During a subsequent 4-year follow-up period, 257 individuals presented incident
      dementia from 8,414 participants, and a subcohort of 1,185 individuals without
      dementia was drawn as a control cohort. Plasma levels of Abeta(1-40), Abeta(1
      42), Abeta(n-40), and Abeta(n-42) were measured using an xMAP-based assay
      technology. The association between plasma Abeta peptide levels and the risk of
      dementia was assessed using Cox proportional hazard models. RESULTS: Of the
      various Abeta variables analyzed, the Abeta(1-42)/Abeta(1-40) and Abeta(n
      42)/Abeta(n-40) ratios presented the strongest association with the risk of
      dementia: people with a high Abeta(1-42)/Abeta(1-40) or Abeta(n-42)/Abeta(n-40)
      ratio had a lower risk of developing dementia. These associations were restricted
      to individuals diagnosed at 2 years of follow-up and the Abeta(n-42)/Abeta(n-40)
      ratio was mainly associated with the risk of mixed/vascular dementia. CONCLUSION:
      Plasma Abeta peptide concentrations and Abeta(1-42)/Abeta(1-40) and Abeta(n
      42)/Abeta(n-40) ratios may be useful markers to indicate individuals susceptible
      to short-term risk of dementia.

PMID- 19752452
TI  - Leisure activities and the risk of dementia in the elderly: results from the
      Three-City Study.
AB  - OBJECTIVE: There is accumulating evidence that involvement in leisure activities
      may be related to risk of dementia; however, there is no consensus concerning the
      underlying mechanism of this association. Hypothesizing that leisure activities
      may contribute to cognitive reserve (CR), we examined the association between
      leisure activities and risk of incident dementia and its subtypes within a
      general population sample, categorizing leisure activity as stimulating, passive,
      physical, and social. The possibility that these associations may be driven by
      other proxies of CR was also examined. METHODS: Analyses were carried out on
      5,698 dementia-free participants aged 65 and over included in the Three-City
      cohort study in Dijon and Montpellier (France) in 1999-2001. Hazard ratios (HR)
      were calculated for incident dementia and its subtypes (mixed/vascular dementia
      and Alzheimer disease) in relation to category of leisure activity. RESULTS:
      Stimulating leisure activities were found to be significantly associated with a
      reduced risk of dementia (n = 161, HR = 0.49, 95% confidence interval [CI]: 0.31;
      0.79) and Alzheimer disease (n = 105, HR = 0.39, 95% CI: 0.21; 0.71) over the 4
      year follow-up 1) independently of other proxies of CR, 2) after adjusting for
      vascular risk factors, depressive symptoms, and physical functioning, and 3)
      independently of other leisure activities. Furthermore, no significant
      association was found with other leisure activities and dementia after
      controlling for the potential confounders. CONCLUSION: Our findings support the
      hypothesis that cognitively stimulating leisure activities may delay the onset of
      dementia in community-dwelling elders.

PMID- 19752453
TI  - Retinal microvascular abnormalities and cognitive decline: the ARIC 14-year
      follow-up study.
AB  - BACKGROUND: Because retinal and cerebral arterioles share similar pathologic
      processes, retinal microvascular changes are expected to be markers of cerebral
      small vessel disease (SVD). To better understand the role of SVD in cognitive
      function, we investigated the relationship between retinal microvascular
      abnormalities and longitudinal changes in cognitive function in a community-based
      study. METHODS: A total of 803 participants underwent 4 cognitive assessments
      between 1990-1992 and 2004-2006, using the Word Fluency (WF) test, Digit Symbol
      Substitution (DSS), and Delayed Word Recall as well as retinal photography in
      1993-1995. Covariate adjusted random effects linear models for repeated measures
      were used to determine the associations of cognitive change with specific retinal
      vascular abnormalities. RESULTS: Individuals with retinopathy showed declines in
      executive function and psychomotor speed, with 1) an average decline in WF of 
      1.64 words per decade (95% confidence interval [CI] -3.3, -0.02) compared to no
      decline in those without retinopathy +0.06 (95% CI -0.6, 0.8) and 2) a higher
      frequency of rapid decliners on the DSS test. CONCLUSION: Signs of retinal
      vascular changes, as markers of the cerebral microvasculature, are associated
      with declines in executive function and psychomotor speed, adding to the growing
      evidence for the role of microvascular disease in cognitive decline in the
      elderly.

PMID- 19752454
TI  - Noninvasive MR imaging of cerebral perfusion in patients with a carotid artery
      stenosis.
AB  - BACKGROUND: Arterial spin labeling (ASL) perfusion MRI with image acquisition at
      multiple delay times can be used to measure delays in the arrival of arterial
      blood to the brain. We assessed the effect of a symptomatic internal carotid
      artery (ICA) stenosis on ASL timing parameters, and evaluated the effect of
      collateral flow through the circle of Willis. METHODS: Forty-four functionally
      independent patients (30 men, 69 +/- 9 years) with a recently symptomatic ICA
      stenosis > or =50% and 34 sex-matched and age-matched healthy volunteers were
      investigated. Magnetic resonance angiography and 2-dimensional phase-contrast
      imaging were used to assess collateral flow in the circle of Willis. RESULTS: In
      the hemisphere ipsilateral to the ICA stenosis, cerebral blood flow (CBF) was
      lower (p < 0.01) in the anterior frontal, posterior frontal, parieto-occipital,
      and occipital regions than in control subjects. The transit times were prolonged
      (p < 0.01) in the ipsilateral anterior frontal, posterior frontal, and
      frontoparietal regions when compared with the control subjects. The trailing edge
      time was prolonged (p < 0.01) in the ipsilateral frontoparietal region when
      compared to the control subjects. In the 27 patients without a contralateral
      stenosis, the trailing edge was longer (p < 0.01) in the ipsilateral posterior
      frontal, frontoparietal, and parieto-occipital regions than in the contralateral
      regions. Collateral flow via the circle of Willis did not affect CBF and transit
      or trailing edge times. CONCLUSION: Arterial spin labeling MRI is a noninvasive
      tool for imaging cerebral blood flow and delays in the arrival of arterial blood
      to the brain, and can potentially provide valuable information on the quality of
      perfusion to the brain in patients with cerebrovascular disease.

PMID- 19752455
TI  - Embolic stroke associated with injection of buprenorphine tablets.
AB  - BACKGROUND: Drug users who crush, dissolve, and inject buprenorphine tablets
      parenterally may be at risk of severe thromboembolic complications or death. We
      describe patients with neurologic complications after injecting buprenorphine
      tablets. METHODS: Brain MRI including diffusion-weighted imaging (DWI) in
      patients admitted to the neurologic department after injecting buprenorphine
      tablets were reviewed. RESULTS: Seven men had neurologic complications after
      buprenorphine tablet injection. In 5 patients, multiple small scattered
      hyperintense lesions were detected on DWI in the cortex, white matter, and basal
      ganglia of the cerebral hemisphere; one patient had a single small lesion. The
      side of MRI abnormality corresponded to the side of needle marks on the neck
      except in one patient who had bilateral injections. One patient, who denied
      injecting into the neck, had DWI abnormalities in the middle cerebral artery
      territory on one side and occlusion of the ipsilateral internal carotid artery.
      CONCLUSIONS: Buprenorphine tablets can be intentionally or inadvertently injected
      into the carotid artery, causing a characteristic appearance on diffusion
      weighted imaging, consistent with embolic cerebral infarction.

PMID- 19752456
TI  - Serotonergic modulation of basal ganglia circuits: complexity and therapeutic
      opportunities.

PMID- 19752458
TI  - Ataxia with ophthalmoplegia or sensory neuropathy is frequently caused by POLG
      mutations.

PMID- 19752457
TI  - Practice parameter: Evaluation of the child with microcephaly (an evidence-based
      review): report of the Quality Standards Subcommittee of the American Academy of
      Neurology and the Practice Committee of the Child Neurology Society.
AB  - OBJECTIVE: To make evidence-based recommendations concerning the evaluation of
      the child with microcephaly. METHODS: Relevant literature was reviewed,
      abstracted, and classified. RECOMMENDATIONS were based on a 4-tiered scheme of
      evidence classification. RESULTS: Microcephaly is an important neurologic sign
      but there is nonuniformity in its definition and evaluation. Microcephaly may
      result from any insult that disturbs early brain growth and can be seen in
      association with hundreds of genetic syndromes. Annually, approximately 25,000
      infants in the United States will be diagnosed with microcephaly (head
      circumference <-2 SD). Few data are available to inform evidence-based
      recommendations regarding diagnostic testing. The yield of neuroimaging ranges
      from 43% to 80%. Genetic etiologies have been reported in 15.5% to 53.3%. The
      prevalence of metabolic disorders is unknown but is estimated to be 1%. Children
      with severe microcephaly (head circumference <-3 SD) are more likely (
      approximately 80%) to have imaging abnormalities and more severe developmental
      impairments than those with milder microcephaly (-2 to -3 SD; approximately 40%).
      Coexistent conditions include epilepsy ( approximately 40%), cerebral palsy (
      approximately 20%), mental retardation ( approximately 50%), and ophthalmologic
      disorders ( approximately 20% to approximately 50%). RECOMMENDATIONS:
      Neuroimaging may be considered useful in identifying structural causes in the
      evaluation of the child with microcephaly (Level C). Targeted and specific
      genetic testing may be considered in the evaluation of the child with
      microcephaly who has clinical or imaging abnormalities that suggest a specific
      diagnosis or who shows no evidence of an acquired or environmental etiology
      (Level C). Screening for coexistent conditions such as cerebral palsy, epilepsy,
      and sensory deficits may also be considered (Level C). Further study is needed
      regarding the yield of diagnostic testing in children with microcephaly.

PMID- 19752459
TI  - Interferon beta treatment does not induce organ-specific autoantibodies in
      multiple sclerosis.

PMID- 19752460
TI  - The imaging spectrum of neuro-Behcet disease.

PMID- 19752461
TI  - Media coverage of the persistent vegetative state and end-of-life decision
      making: Theresa Schiavo's tragedy and ours, too.

PMID- 19752462
TI  - The intriguing case of Christina the Astonishing.

PMID- 19752463
TI  - Obama's vision and the prospects for health care reform.

PMID- 19752464
TI  - Physicians' beliefs and U.S. health care reform--a national survey.

PMID- 19752465
TI  - Doctors on coverage--physicians' views on a new public insurance option and
      Medicare expansion.

PMID- 19752466
TI  - A science of connectedness.

PMID- 19752467
TI  - Universal health insurance and equity in primary care and specialist office
      visits: a population-based study.
AB  - PURPOSE: Universal coverage of physician services should serve to reduce
      socioeconomic disparities in care, but the degree to which a reduction occurs is
      unclear. We examined equity in use of physician services in Ontario, Canada,
      after controlling for health status using both self-reported and diagnosis-based
      measures. METHODS: Ontario respondents to the 2000-2001 Canadian Community Health
      Survey (CCHS) were linked with physician claim files in 2002-2003 and 2003-2004.
      Educational attainment and income were based on self-report. The CCHS was used
      for self-reported health status and Johns Hopkins Adjusted Clinical Groups was
      used for diagnosis-based health status. RESULTS: After adjustment, higher
      education was not associated with at least 1 primary care visit (odds ratio [OR]
      = 1.05; 95% confidence interval [CI], 0.87-1.24), but it was inversely associated
      with frequent visits (OR = 0.77; 95% CI, 0.65-0.88). Higher education was
      directly associated with at least 1 specialist visit (OR = 1.20; 95% CI, 1.07
      1.34), with frequent specialist visits (OR = 1.21; 95% CI, 1.03-1.39), and with
      bypassing primary care to reach specialists (OR = 1.23, 95% CI 1.02-1.44). The
      largest inequities by education were found for dermatology and ophthalmology.
      Income was not independently associated with inequities in physician contact or
      frequency of visits. CONCLUSIONS: After adjusting for health status, we found
      equity in contact with primary care for educational attainment but inequity in
      specialist contact, frequent visits, and bypassing primary care. In this setting,
      universal health insurance appears to be successful in achieving income equity in
      physician visits. This strategy alone does not eliminate education-related
      gradients in specialist care.

PMID- 19752468
TI  - Children's receipt of health care services and family health insurance patterns.
AB  - PURPOSE: Insured children in the United States have better access to health care
      services; less is known about how parental coverage affects children's access to
      care. We examined the association between parent-child health insurance coverage
      patterns and children's access to health care and preventive counseling services.
      METHODS: We conducted secondary analyses of nationally representative, cross
      sectional, pooled 2002-2006 data from children (n = 43,509), aged 2 to 17 years,
      in households responding to the Medical Expenditure Panel Survey (MEPS). We
      assessed 9 outcome measures pertaining to children's unmet health care and
      preventive counseling needs. RESULTS: Cross-sectionally, among US children (aged
      2 to 17 years) living with at least 1 parent, 73.6% were insured with insured
      parents, 8.0% were uninsured with uninsured parents, and the remaining 18.4% had
      discordant family insurance coverage patterns. In multivariable analyses, insured
      children with uninsured parents had higher odds of an insurance coverage gap
      (odds ratio [OR] = 2.45; 95% confidence interval [CI], 2.02-2.97), no usual
      source of care (OR = 1.31; 95% CI, 1.10-1.56), unmet health care needs (OR =
      1.11; 95% CI, 1.01-1.22), and having never received at least 1 preventive
      counseling service (OR = 1.20; 95% CI, 1.04-1.39) when compared with insured
      children with insured parents. Insured children with mixed parental insurance
      coverage had similar vulnerabilities. CONCLUSIONS: Uninsured children had the
      highest rates of unmet needs overall, with fewer differences based on parental
      insurance status. For insured children, having uninsured parents was associated
      with higher odds of going without necessary services when compared with having
      insured parents.

PMID- 19752469
TI  - Depression and increased mortality in diabetes: unexpected causes of death.
AB  - PURPOSE: Recent evidence suggests that depression is linked to increased
      mortality among patients with diabetes. This study examines the association of
      depression with all-cause and cause-specific mortality in diabetes. METHODS: We
      conducted a prospective cohort study of primary care patients with type 2
      diabetes at Group Health Cooperative in Washington state. We used the Patient
      Health Questionnaire (PHQ-9) to assess depression at baseline and reviewed
      medical records supplemented by the Washington state mortality registry to
      ascertain the causes of death. RESULTS: Among a cohort of 4,184 patients, 581
      patients died during the follow-up period. Deaths occurred among 428 (12.9%)
      patients with no depression, among 88 (17.8%) patients with major depression, and
      among 65 (18.2%) patients with minor depression. Causes of death were grouped as
      cardiovascular disease, 42.7%; cancer, 26.9%; and deaths that were not due to
      cardiovascular disease or cancer, 30.5%. Infections, dementia, renal failure, and
      chronic obstructive pulmonary disease were the most frequent causes in the latter
      group. Adjusting for demographic characteristics, baseline major depression
      (relative to no depression) was significantly associated with all-cause mortality
      (hazard ratio [HR]=2.26, 95% confidence interval [CI], 1.79-2.85), with
      cardiovascular mortality (HR = 2.00; 95% CI, 1.37-2.94), and with
      noncardiovascular, noncancer mortality (HR = 3.35; 95% CI, 2.30-4.89). After
      additional adjustment for baseline clinical characteristics and health habits,
      major depression was significantly associated only with all-cause mortality (HR =
      1.52; 95% CI, 1.19-1.95) and with death not caused by cancer or atherosclerotic
      cardiovascular disease (HR = 2.15; 95% CI, 1.43-3.24). Minor depression showed
      similar but nonsignificant associations. CONCLUSIONS: Patients with diabetes and
      coexisting depression face substantially elevated mortality risks beyond
      cardiovascular deaths.

PMID- 19752470
TI  - Yield of opportunistic targeted screening for type 2 diabetes in primary care:
      the diabscreen study.
AB  - PURPOSE: In screening for type 2 diabetes, guidelines recommend targeting high
      risk individuals. Our objectives were to assess the yield of opportunistic
      targeted screening for type 2 diabetes in primary care and to assess the
      diagnostic value of various risk factors. METHODS: In 11 family practices (total
      practice population = 49,229) in The Netherlands, we conducted a stepwise
      opportunistic screening program among patients aged 45 to 75 years by (1)
      identifying high-risk individuals (=1 diabetes risk factor) and low-risk
      individuals using the electronic medical record, (2) obtaining a capillary
      fasting plasma glucose measurement, repeated on a separate day if the value was
      greater than 110 mg/dL, and (3) obtaining a venous sample if both capillary
      fasting plasma glucose values were greater than 110 mg/dL and at least 1 sample
      was 126 mg/dL or greater. We calculated the yield (percentage of invited patients
      with undiagnosed diabetes), number needed to screen (NNS), and diagnostic value
      of the risk factors (odds ratio and area under the receiver operating
      characteristic curve). RESULTS: We invited for a first capillary measurement
      3,724 high-risk patients seen during usual care and a random sample of 465 low
      risk patients contacted by mail. The response rate was 90% and 86%, respectively.
      Ultimately, 101 high-risk patients (2.7%; 95% confidence interval [CI], 2.2%
      3.3%; NNS = 37) and 2 low-risk patients (0.4%; 95% CI, 0.1%-1.6%; NNS = 233) had
      undiagnosed diabetes (P <.01). The prevalence of diabetes among patients 45 to 75
      years old increased from 6.1% to 6.8% as a result. Among diagnostic models
      containing various risk factors, a model containing obesity alone was the best
      predictor of undiagnosed diabetes (odds ratio = 3.2; 95% CI, 2.0-5.2; area under
      the curve=0.63). CONCLUSIONS: The yield of opportunistic targeted screening was
      fair; obesity alone was the best predictor of undiagnosed diabetes. Opportunistic
      screening for type 2 diabetes in primary care could target middle-aged and older
      adults with obesity.

PMID- 19752471
TI  - Availability of antibiotics for purchase without a prescription on the internet.
AB  - PURPOSE: Reducing inappropriate use of antibiotics is key to many antibiotic
      resistance initiatives. Most initiatives, however, focus almost exclusively on
      controlling prescribing by health care clinicians and do not focus on patient
      self-medication. The purpose of this study was to examine antibiotics available
      to patients without a prescription, a phenomenon on the Internet. METHODS: We
      conducted an Internet search using 2 major search engines (Google and Yahoo) with
      the key words "purchase antibiotics without a prescription" and "online (English
      only)." Vendors were compared according to the classes of antibiotics available,
      quantity, shipping locations, and shipping time. RESULTS: We found 138 unique
      vendors selling antibiotics without a prescription. Of those vendors, 36.2% sold
      antibiotics without a prescription, and 63.8% provided an online prescription.
      Penicillins were available on 94.2% of the sites, macrolides on 96.4%,
      fluoroquinolones on 61.6%, and cephalosporins on 56.5%. Nearly all, 98.6%, ship
      to the United States. The mean delivery time was 8 days, with 46.1% expecting
      delivery in more than 7 days. Among those selling macrolides (n = 133), 93.3%
      would sell azithromycin in quantities consistent with more than a single course
      of medication. Compared with vendors that require a medical interview, vendors
      who sell antibiotics without a prescription were more likely to sell quantities
      in excess of a single course, and the antibiotics were more likely to take more
      than 7 days to reach the customer. CONCLUSIONS: Antibiotics are freely available
      for purchase on the Internet without a prescription, a phenomenon that encourages
      self-medication and low quality of care.

PMID- 19752472
TI  - Motivational intervention to reduce rapid subsequent births to adolescent
      mothers: a community-based randomized trial.
AB  - PURPOSE: One-quarter of adolescent mothers bear another child within 2 years,
      compounding their risk of poorer medical, educational, economic, and parenting
      outcomes. Most efforts to prevent rapid subsequent birth to teenagers have been
      unsuccessful but have seldom addressed motivational processes. METHODS: We
      conducted a randomized trial to determine the effectiveness of a computer
      assisted motivational intervention (CAMI) in preventing rapid subsequent birth to
      adolescent mothers. Pregnant teenagers (N = 235), aged 18 years and older who
      were at more than 24 weeks' gestation, were recruited from urban prenatal clinics
      serving low-income, predominantly African American communities. After completing
      baseline assessments, they were randomly assigned to 3 groups: (1) those in CAMI
      plus enhanced home visit (n = 80) received a multi-component home-based
      intervention (CAMI+); (2) those in CAMI-only (n = 87) received a single component
      home-based intervention; (3) and those in usual-care control (n = 68) received
      standard usual care. Teens in both intervention groups received CAMI sessions at
      quarterly intervals until 2 years' postpartum. Those in the CAMI+ group also
      received monthly home visits with parenting education and support. CAMI
      algorithms, based on the transtheoretical model, assessed sexual relationships
      and contraception-use intentions and behaviors, and readiness to engage in
      pregnancy prevention. Trained interventionists used CAMI risk summaries to guide
      motivational interviewing. Repeat birth by 24 months' postpartum was measured
      with birth certificates. RESULTS: Intent-to-treat analysis indicated that the
      CAMI+ group compared with the usual-care control group exhibited a trend toward
      lower birth rates (13.8% vs 25.0%; P = .08), whereas the CAMI-only group did not
      (17.2% vs 25.0%; P = .32). Controlling for baseline group differences, the hazard
      ratio (HR) for repeat birth was significantly lower for the CAMI+ group than it
      was with the usual-care group (HR = 0.45; 95% CI, 0.21-0.98). We developed
      complier average causal effects models to produce unbiased estimates of
      intervention effects accounting for variable participation. Completing 2 or more
      CAMI sessions significantly reduced the risk of repeat birth in both groups:
      CAMI+ (HR = 0.40; 95% CI, 0.16-0.98) and CAMI-only (HR = 0.19; 95% CI, 0.05
      0.69). CONCLUSIONS: Receipt of 2 or more CAMI sessions, either alone or within a
      multicomponent home-based intervention, reduced the risk of rapid subsequent
      birth to adolescent mothers.

PMID- 19752473
TI  - Management decisions in nontraumatic complaints of arm, neck, and shoulder in
      general practice.
AB  - OBJECTIVE We wanted to evaluate associations between diagnosis and
      characteristics of the patient, complaint, and general practitioner (GP), as well
      as 6 common management decisions, in patients with nontraumatic arm, neck, and
      shoulder complaints at the time of the first consultation with their physician.
      METHODS: We undertook an observational cohort study set in 21 Dutch general
      practices, including 682 patients with nontraumatic complaints of arm, neck, and
      shoulder. The outcome measure was application (yes/no) of a specific management
      option: watchful waiting, additional diagnostic tests, prescription of
      medication, corticosteroid injection, referral for physiotherapy, and referral
      for medical specialist care. RESULTS: Separate multilevel analyses showed that
      overall, the diagnostic category, having long duration of complaints, and
      reporting many functional limitations were most frequently associated with the
      choice of a management option. For watchful waiting, only complaint variables
      played a role (long duration of complaints, high complaint severity, many
      functional limitations, recurrent complaint). All these variables were negatively
      associated with watchful waiting. When opting for 1 of the 5 other management
      options, several physician characteristics played a role as well. Less clinical
      experience was associated with additional diagnostic tests and referral to a
      medical specialist. GPs working in a solo practice more frequently referred to a
      medical specialist. GPs working in a rural area more frequently referred for
      physiotherapy. Female GPs prescribed medication less frequently. Physicians with
      special interest in musculoskeletal complaints gave corticosteroid injections
      more frequently. CONCLUSIONS: Diagnostic category, long duration of complaints,
      and high functional limitations were key variables in management decisions with
      these complaints. In addition, several physician characteristics played a role as
      well.

PMID- 19752477
TI  - Impact of expanding use of health information technologies on medical student
      education in family medicine.

PMID- 19752474
TI  - Diagnostic accuracy of Spanish language depression-screening instruments.
AB  - PURPOSE: To make decisions about implementing systematic depression screening,
      primary care physicians who serve Spanish-speaking populations need to know
      whether Spanish language depression-screening instruments are accurate. We aimed
      to review systematically the evidence regarding diagnostic accuracy of depression
      screening instruments in Spanish-speaking primary care populations. METHODS: We
      searched PubMed, PsycINFO, CINAHL, EMBASE, and Cochrane Libraries from inception
      to May 28, 2008, for studies examining the diagnostic accuracy of Spanish
      language depression case-finding instrument(s) administered to primary-care
      outpatients. Two authors independently assessed studies for inclusion and
      quality. RESULTS: Twelve studies met inclusion criteria. In general primary care
      screening, the Spanish language version of the Center for Epidemiologic Studies
      Depression scale (CES-D) had sensitivities ranging from 76% to 92% and
      specificities ranging from 70% to 74%. We found no US study reporting the
      accuracy of the Primary Care Evaluation of Mental Disorders (PRIME-MD-9) or the
      Patient Health Questionnaire (PHQ-9) depression module in Spanish-speakers. One
      fair-quality European study and 1 poor-quality study conducted in Honduras found
      the 9-item PRIME-MD had sensitivities ranging from 72% to 77% and specificities
      ranging from 86% to 100%. The 2-item PRIME-MD was 92% sensitive, but only 44%
      specific for depression in 1 US study. In geriatric outpatients, the 15-item
      Spanish language version of the Geriatric Depression Scale (GDS) had
      sensitivities ranging from 76% to 82%, and specificities ranging from 64% to 98%.
      In postpartum women, the Spanish language version of the Edinburgh Postnatal
      Depression Scale (EPDS) was 72% to 89% sensitive and 86% to 95% specific for
      major depression (2 non-US studies). The Spanish language version of the
      Postpartum Depression Screening Scale (PDSS) was 78% sensitive and 85% specific
      for combined major/minor depression (1 US study). CONCLUSIONS: For depression
      screening in Spanish-speaking outpatients, fair evidence supports the diagnostic
      accuracy of the CES-D and PRIME-MD-9 in general primary care, the GDS-15-Spanish
      for geriatric patients, and the Spanish language versions of the EPDS or PDSS for
      postpartum patients. The ultrashort 2-item version of PRIME-MD may lack
      specificity in US Spanish-speakers.

PMID- 19752478
TI  - Is the family physician in or out of hospital medicine? A discussion of pertinent
      perspectives to consider as we address inpatient curricular review.

PMID- 19752481
TI  - Pepsinogen I concentration in organic dyspepsia patients at Gastroenterology
      Division, Department of Internal Medicine, Cipto Mangunkusumo Hospital.
AB  - AIM: To study Pepsinogen I (PG I) concentration in atrophic chronic gastritis
      (ACG) and non-atrophic chronic gastritis (NACG) patients with or without H.
      pylori infection compared to gastroscopy and biopsy as the gold standard.
      METHODS: The study subjects consisted of 70 organic dyspepsia patients who
      underwent esofago gastroduodenoscopy (EGD) at the Gastroenterology Outpatient
      Clinic Department of Internal Medicine Cipto Mangunkusumo Hospital. Pepsinogen I
      tests were performed using ELISA with Human Pepsinogen I ELISA kit from Biohit.
      The data analysis used the SPSS 13 program. The ROC curve was used to find the
      cut off point with the best sensitivity and specificity. The proportion of
      positive H. Pylori was measured in percentage. RESULTS: From the 70 organic
      dyspepsia patients, there were 37 subjects (52.8%) that have histopathological
      findings of NACG and 26 subjects (37.1%) ACG. The best cut off point for PG I
      concentration to predict ACG is 119 microg/L (sensitivity 70%, specificity 50%).
      The value of PG I concentrations between NACG and ACG patients did not differ
      significantly at 0.485 (p > 0.05). CONCLUSION: The cut off point for PG I
      concentrations in this study did not differ significantly between NACG and ACG
      patients.

PMID- 19752482
TI  - The views of general practitioners in Iran about prevention and health promotion
      and related obstacles in clinical practice.
AB  - AIM: To explore the awareness and attitudes of Iranian GPs in implementing
      evidence-based health promotion and disease prevention recommendations in primary
      care and to describe GPs' perceived barriers to implementing these
      recommendations. METHODS: Our survey was carried out in 2007 in a random sample
      of GPs listed from an educational symposiums held for general practitioners. We
      developed and pre-tested a questionnaire, it was piloted with 417 GPs in general
      practitioners educational symposiums attending all parts of Iran. Those who did
      not respond received follow-up mailings and/or telephone calls. Our data
      management center started data entry and analyzing as soon as the questionnaires
      were sent back. Discrete variables were expressed as percentages and were
      compared with the chi-square test or Fisher's exact test as appropriate.
      Continuous variables were compared by means of the unpaired, two-sided t test.
      All statistical analyses were performed using SPSS software Version 13.
      Statistical significance was accepted for P<0.05. RESULTS: Four hundred and
      seventeen GPs participated in the study. Although they believe they should advise
      preventive and health promotion activities, in practice, they are less likely to
      do so. The two most important barriers reported were weak patients' interest in
      screening tests no reimbursement for GPs. Associations between personal health
      behaviour and attitudes to health promotion or activities in prevention were
      found. GPs who exercised felt that they were more effective in helping patients
      to practice regular physical exercise than sedentary GPs. (P<0.001). CONCLUSION:
      Significant gaps between GP's knowledge and practices persist in the use of
      evidence-based recommendations for health promotion and disease prevention in
      primary care.

PMID- 19752483
TI  - Blood glucose level in neurosurgery. Is it different between isoflurane and
      desflurane anesthesia?
AB  - AIM: A tight control of blood glucose is critical. We compare blood glucose level
      between isoflurane and desflurane in neurosurgical patients for further
      application. METHODS: One hundred and eight patients scheduled for neurosurgery
      under general anesthesia were recruited and divided into two groups; fentanyl
      isoflurane-nitrous oxide based and fentanyl-desflurane-nitrous oxide based
      randomly. Vital signs, end tidal gas concentration, amount of narcotics usage and
      blood glucose level were recorded at induction (T0) and intraoperative hourly
      thereafter (T1-T8). Independent t-test and ANOVA were used. The statistical
      significance was considered if p-value < 0.05. RESULTS: There were 107 patients
      enrolled excluded one from isoflurane group because of the schedule changes. The
      amounts of fentanyl usage (0.89+/-0.41 mcg/kg/hr, 0.88+/-0.48 mcg/kg/hr), the end
      tidal inhales' tension (0.71%+/-0.32, 3.13%+/-1.63) were equivalent in isoflurane
      and desflurane group. The blood glucose levels at various period of time had no
      statistical difference but there was a significant (p<0.05) increasing from T1 to
      T8 comparing to T0 in both groups (3.88+/-0.93 mg%/hr and 5.55+/-1.14 mg%/hr).
      CONCLUSION: Desflurane has demonstrated the indistinguishable blood glucose level
      and hemodynamic response from isoflurane anesthesia intraoperatively in
      neurosurgical patients, confirming a comparable pattern of blood glucose
      concentration intensifying over time spends.

PMID- 19752484
TI  - Hematologic manifestation of avian influenza patients in hasan sadikin hospital.
AB  - AIM: To investigate the hematologic manifestation and the relationship of the
      abnormalities with mortality. METHODS: We examined hematologic data from 10 Avian
      influenza patients in Hasan Sadikin Hospital Bandung between November 2005 and
      March 2007. RESULTS: The mortality rate was 70%. Anemia was found in 30% (3 of 10
      patients). Leukopenia was found in 60% (6 of 10 patients. Lymphopenia and
      neutropenia were found in 50% (4 of 8 patients) and 62.5% (5 of 8 patients).
      Sixty percent (6 of 10 patients) had thrombocytopenia. Anemia was not correlated
      with mortality (OR=0.08). Leukopenia, neutropenia and lymphopenia were correlated
      with mortality (OR=5, OR=8 and OR=12, respectively). Thrombocytopenia was also
      correlated with mortality (OR=5). CONCLUSION: Leukopenia, neutropenia,
      lymphopenia and thrombocytopenia were common findings among avian influenza
      patients in Hasan Sadikin Hospital. Decreased white blood cells and platelets
      were correlated with mortality.

PMID- 19752485
TI  - Grade 3-4 liver enzyme elevation during HAART in HIV and hepatitis C co-infected
      adults.
AB  - AIM: To evaluate the incidence of grade 3-4 LEE in HIV/HCV co-infected patients
      after the introduction of HAART, the clinical significance to the patients and to
      determine any factors that could predict its development. METHODS: A
      retrospective cohort study of HIV/HCV co-infected adults in Pokdisus AIDS Clinic
      Cipto Mangunkusumo Hospital was conducted. All patients were antiretroviral naive
      and had never had interferon therapy before. Patients who started taking fist
      line combination therapy in Indonesia (NNRTI based regimen) from January 2004 to
      August 2006 and who were followed up for at least 6 months later were included in
      this study. RESULTS: A total of 59 grade 3-4 LEE (any ALT increase by > 5 times
      ULN or any increase of 100 U/L from baseline) developed in 284 patients during
      the follow up (20.8%). The median onset of grade 3-4 LEE was 20 weeks (min-max 2
      80). Only 27.1% accompanied with symptoms. Two patients developed decompensated
      liver diseases, one of them ended with death. In 5 patients, grade 3-4 LEE
      coincided with nevirapine or efavirenz-related rashes. Fifty-two patients (88.1%)
      continued their antiretroviral regimen throughout the entire episode of grade 3-4
      LEE. The median peak level of ALT was 2311 IU/L (IQR, 174-327). CONCLUSION: Lower
      baseline ALT was the only factor significantly correlated with grade 3-4 LEE in
      this study.

PMID- 19752486
TI  - Expression of B-type natriuretic peptide-45 (BNP-45) gene in the ventricular
      myocardial induced by systemic chronic hypoxia.
AB  - AIM: To investigate the expression of B-type natriuretic peptide-45 (BNP-45) gene
      which was induced by systemic chronic hypoxia, and whether these changes would be
      different from BNP-45 protein in the plasma and its mRNA in the ventricular
      myocardial. This study also aimed to test the hypothesis that systemic chronic
      hypoxia may cause heart failure. METHODS: Although clinical use of BNP as a
      biomarker in heart failure is increasing, the specificity of BNP for heart
      failure is not robust, suggesting that other mechanisms beyond simple ventricular
      stretch stimulate BNP release. Plasma BNP levels were markedly increased in
      patients with coronary artery disease but without concomitant left ventricular
      dysfunction. Thus, elevated BNP levels do not necessarily reflect heart failure
      but may also result from cardiac ischemia. Sprague-Dawley male rats, weighing 220
      250 g at the time of recruitment were randomly divided into 7 groups (n = 4 per
      group), the control normoxia group was exposed to room air, while the hypoxia
      group were caged in a plexiglass hypoxic chamber (8%O2 and 92% N2) for 1, 3, 7,
      14, 21, and 28 days, respectively. RESULTS: Our data clearly showed that plasma
      BNP-45 and ventricular BNP-45 mRNA concentration were markedly increased which
      reached its peak on day 21 after treatment. CONCLUSION: Regulation of BNP-45 gene
      expression occurred at transcription as well as post-transcription level.
      Systemic chronic hypoxia could result in heart failure, especially when the
      hypoxia is severe and prolonged.

PMID- 19752487
TI  - Endoscopic ultrasound in the diagnosis of occult pancreatic head cancer.
AB  - Two consecutive female patients presented with progressive jaundice, epigastric
      pain and weight loss. Cross-sectional imaging with computer tomography and
      magnetic resonance imaging did not show any mass lesions whereas magnetic
      resonance cholangiopancreatography showed common bile duct strictures. Both
      patients were then referred for endosonographic evaluation. Endoscopic ultrasound
      showed occult pancreatic head masses in both cases and endoscopic ultrasound
      guided fine needle aspiration confirmed the diagnosis of pancreatic cancer. Both
      patients then successfully underwent endoscopic palliation with endoscopic
      ultrasound guided celiac plexus neurolysis and insertion of self expandable
      metallic biliary stents. This case is reported to describe the diagnostic and
      therapeutic impact of endoscopic ultrasound in the management of occult
      pancreatic head cancer. Endoscopic ultrasound is useful in the management of
      pancreatic cancer. It can detect occult pancreatic lesions, provide tissue
      diagnosis and facilitate pain palliation.

PMID- 19752488
TI  - Clostridium difficile infection in the elderly.
AB  - The aging society and the advanced of supportive treatment means that large
      numbers of elderly patients with risk factors for C difficile enterocolitis will
      continue to receive care in intensive care unit. Antibiotic resistance and older,
      sicker patients means that combination antibiotic therapy will become a trend in
      clinical setting. Age, several co-morbidities, and gastrointestinal surgery
      appear to be specific risk factors for C difficile infection. Diarrhea which is
      the only symptom in hospitalized patient should drive us to rethink about the
      possibility of C difficile infection especially in the elderly patient. Prudent
      use of antibiotic, infection control are strategies to prevent C difficile
      infection in clinical setting. Elderly patients who undergo gastrointestinal
      surgery have an increased rate of C difficile infection because of commonly used
      nasogastric tube. Gastrointestinal surgical patients typically have preoperative
      bowel preparation, receive oral preoperative antibiotics that are poorly
      absorbed, impaired bowel motility secondary to ileus, receive systemic
      preoperative antibiotics prophylaxis, and have variable lengths of no oral
      caloric intake during the preoperative period. The continued imprudent use of
      prolonged postoperative systemic antibiotics for presumed preventive purposes,
      particularly among the elderly and patients who have nasogastric tubes or other
      enteric tubes, appears to be a recipe for preventable infections with C
      difficile.

PMID- 19752489
TI  - Congenital right coronary artery (RCA) abberant arises from left circumflex
      artery (LCX).
AB  - Female, 55 year old with history of long standing hypertension and diabetes, came
      to ER in a hospital with decreased consciousness. The pulse was irregular and ECG
      showed recurrent Ventricular Tachycardia (VT). After immediate intervention, she
      was finally survived and admitted to Intensive coronary care Unit (ICCU). Cardiac
      troponin was positive. She was considered to have acute coronary syndrome. The
      Brain CT showed ischemic lesion. During hospitalization, coronary angiography was
      performed. It showed left dominant coronary artery and very small right coronary
      artery (RCA) with no RCA ostial at the aorta. There was 50% stenosis in Left
      Descending Artery (LAD) and 30% in Left Circumflex (LCX). Total occlusion caused
      by thrombus at the RCA ostial was suspected. The cardiac MSCT was then performed
      to confirm the result. The MSCT showed no ostial of RCA at aorta and suspected
      total occlusion in proximal RCA. The RCA arises from LCX and its vessel was small
      in diameter less than 2 mm.

PMID- 19752490
TI  - Indication for percutaneous coronary angioplasty.
AB  - Percutaneous transluminal coronary angioplasty (PTCA) or balloon angioplasty, was
      performed in the United States, but the technique remained challenged by the
      primary problem of ''re-stenosis'', which was approximately 30% closing of the
      coronary artery after balloon dilatation. When first PTCA introduced by Gruentzig
      in 1977, it was specific directed for patients who have angina, documented
      ischemia, single vessel disease, and proximal lesion (simple lesion). But then by
      the recent advanced in technology including guide wire, balloon, intravascular
      ultrasound, pharmacological therapy particularly of stents, it is than indicated
      in much more complex lesions. The extension of indication of PCI to more complex
      lesion were supported by many studies and clinical trials. Comprehensively
      indication of PCI were summarize in the two most well known guideline, following
      first to European Society of Cardiology (ESC, 2005) and second to the American
      Heart Association (AHA, 2007), American college of cardiology (ACC), and American
      Society of Cardiac Intervention (ASCAI). The latest guidelines for
      appropriateness criteria for coronary Revascularization was just published in Jan
      2009 by The American College of Cardiology, Society for Cardiovascular
      Angiography and Intervention and Society of Thoracic surgery. In this guidelines
      indication of coronary revascularization is assessed following 3 categories which
      is appropriate, uncertain and inappropriate. Basically those guidelines are the
      same, there are differ in applying classification of recommendation and level of
      evidence, the systematic presentation, and the defining appropriateness
      indication of revascularization.

PMID- 19752491
TI  - Functional gene silencing mediated by chitosan/siRNA nanocomplexes.
AB  - Chitosan/siRNA nanoparticles to knock down FHL2 gene expression were reported in
      this work. The physicochemical properties such as particle size, surface charge,
      morphology and complex stability of chitosan nanoparticle-incorporated siRNA were
      evaluated. Nanoparticles which were formulated with chitosan/siRNA exhibited
      irregular, lamellar and dendritic structures with a hydrodynamic radius size of
      about 148 nm and net positive charges with zeta-potential value of 58.5 mV. The
      knockdown effect of the chitosan/siRNA nanoparticles on gene expression in FHL2
      over-expressed human colorectal cancer Lovo cells was investigated. The result
      showed that FHL2 siRNA formulated within chitosan nanoparticles could knock down
      about 69.6% FHL2 gene expression, which is very similar to the 68.8% reduced gene
      expression when siRNA was transfected with liposome Lipofectamine. Western
      analysis further showed significant FHL-2 protein expression reduced by the
      chitosan/siRNA nanoparticles. The results also showed that blocking FHL2
      expression by siRNA could also inhibit the growth and proliferation of human
      colorectal cancer Lovo cells. The current results demonstrated that chitosan
      based siRNA nanoparticles were a very efficient delivery system for siRNA in vivo
      as previously reported.

PMID- 19752492
TI  - The mechanical response of turbostratic carbon nanotubes filled with Ga-doped
      ZnS: I. Data processing for the extraction of the elastic modulus.
AB  - The mechanical response of hybrid carbon nanotubes to applied uniaxial
      compressive forces has been evaluated inside a transmission electron microscope.
      The initially crooked nanocolumnar materials had an average elastic modulus of
      0.53 GPa, measured in situ via a device based on an atomic force microscope
      cantilever. To extract this property it was necessary to curtail several sources
      of error (contact sliding, electronic interferences, etc) and develop the
      methodology herewith outlined. Since the present study was carried out with a
      commercially available sample holder, these mechanical studies are pertinent to
      all those working with one-dimensional structures such as nanorods and nanowires.

PMID- 19752493
TI  - Functional recognition imaging using artificial neural networks: applications to
      rapid cellular identification via broadband electromechanical response.
AB  - Functional recognition imaging in scanning probe microscopy (SPM) using
      artificial neural network identification is demonstrated. This approach utilizes
      statistical analysis of complex SPM responses at a single spatial location to
      identify the target behavior, which is reminiscent of associative thinking in the
      human brain, obviating the need for analytical models. We demonstrate, as an
      example of recognition imaging, rapid identification of cellular organisms using
      the difference in electromechanical activity over a broad frequency range. Single
      pixel identification of model Micrococcus lysodeikticus and Pseudomonas
      fluorescens bacteria is achieved, demonstrating the viability of the method.

PMID- 19752494
TI  - Superparamagnetic magnetite nanocrystal clusters: a sensitive tool for MR
      cellular imaging.
AB  - Silica coated, PEI and citric acid hybrid superparamagnetic magnetite nanocrystal
      clusters (SMNC) were synthesized using either a mini-emulsion/sol-gel method or a
      polyol technique. After careful characterization of the size, structure,
      composition, and magnetic properties, the as-synthesized SMNC were used for cell
      labeling while the MR detection sensitivity of cells labeled with silica SMNC was
      performed with a 3 T whole body MR scanner. TEM investigations revealed that the
      sizes of the SMNC were about 200 nm and the SMNC mainly consisted of magnetite
      nanoparticles imbedded in a PEI, citric acid or polystyrene scaffold. Silica and
      citric acid SMNC were highly negatively charged and PEI SMNC were positively
      charged. Relaxometry measurements revealed that these SMNC possessed a very high
      MR sensitivity (silica SMNC: r(2) = 299 s(-1) mM(-1), PEI SMNC: r(2) = 124 s(-1)
      mM(-1)), especially for the citric acid SMNC (r(2) = 360 s(-1) mM(-1)).
      Furthermore, when used for cell (RAW264.7 cells) labeling, the SMNC had no
      adverse effect on cell viability, and the cell uptake of the SMNC show a dose-
      and time-dependent feature. MR imaging of cells labeled with silica SMNC
      indicated that cells with a concentration as low as 10 x 10(3) cells ml(-1) could
      be detected with a 3 T MRI scanner. Our study demonstrated that superparamagnetic
      magnetite nanocrystal clusters are a sensitive tool for cell imaging.

PMID- 19752495
TI  - Synthesis and performance of bismuth trioxide nanoparticles for high energy gas
      generator use.
AB  - Our experiments showed that the combustion of an Al-Bi2O3 nanoparticle mixture
      generated the highest pressure pulse among common nanothermite reactions and can
      potentially be used as a nanoenergetic gas generator. The combustion front
      propagation velocity and rate of energy release increased by up to three orders
      of magnitude when the particle size was reduced to a nanosize range for both the
      aluminum and the oxidizer. We developed a novel one-step (metal nitrate-glycine)
      combustion synthesis of nanostructured amorphous-like and highly crystalline
      bismuth trioxide nanoparticles. The combustion synthesis was conducted using a
      solution of molten bismuth nitrate as an oxidizer and glycine as a fuel. The
      glycine was completely combusted during the thermal decomposition of the bismuth
      nitrate pentahydrate and generated a temperature front that propagated through
      the sample. Increasing the fuel concentration increased the maximum combustion
      temperature from 280 to 1200 degrees C and the Bi2O3 particle size from 20 to 100
      nm. The oxidizer/fuel ratio had a strong impact on the bismuth trioxide particle
      crystallinity. At low temperature (280 degrees C), amorphous-like bismuth
      trioxide nanoparticles formed, while at T > or =370 degrees C the structures were
      crystalline. A peak pressure of approximately 12 MPa and a thermal front
      propagating velocity of approximately 2500 m s(-1) were achieved during the
      combustion of an Al-Bi2O3 mixture containing 80 wt% of the synthesized Bi2O3
      crystalline nanoparticles (size: 40-50 nm).

PMID- 19752496
TI  - Memory effects based on random networks of single-walled carbon nanotubes.
AB  - We have fabricated memory devices based on random networks of single-walled
      carbon nanotubes (SWNTs) on a glass substrate. The characteristics of the
      nonvolatile memory were investigated as a function of gate voltage, pulse time,
      and temperature. The program/erase window was greater than approximately 3.2 V.
      The gate voltage sensitivity of the erase speed was greater ( approximately 1.9
      times) than that of the program speed. The activation energy was about 0.273 eV.
      The mechanism could be explained from the polarization of water molecules, and
      may provide an important insight into the program/erase operation of memory
      devices. We have also discussed a fast erase speed due to a work function
      difference and oxide trapped charges.

PMID- 19752497
TI  - The monomer-to-dimer transition and bimodal growth of Co-salen on NaCl(001): a
      high resolution atomic force microscopy study.
AB  - Molecules of Co-salen, a paramagnetic metal-organic Schiff base complex, self
      assemble into two different well ordered morphologies on a NaCl(001) substrate:
      nanowires, which form networks, and compact nanocrystallites. Their growth can be
      controlled by adjusting the deposition parameters. It turns out that the
      nanowires are metastable. Molecular resolution images suggest that the packing in
      both morphologies is the same as in bulk Co-salen single crystals. Only the
      orientation of the c-axis with respect to the substrate is different. The origin
      of this intriguing bimodal growth is associated with a monomer-to-dimer
      transition, which probably takes place during initial nucleation at step edges.

PMID- 19752498
TI  - Novel planar field emission of ultra-thin individual carbon nanotubes.
AB  - In this work, we proposed and realized a new prototype of planar field emission
      device based on as-grown individual carbon nanotubes (CNTs) on the surface of a
      Si-SiO2 substrate. The anode, cathode and the CNT tip all lie on the same
      surface, so the electron emission is reduced from three-dimensional to two
      dimensional. The benefits of such a design include usage of thinner CNT emitters,
      integrity with planar technology, stable construction, better heat dissipation,
      etc. A tip-to-tip field emission device was presented besides the tip-to
      electrode one. Real-time, in situ observation of the planar field emission was
      realized in a scanning electron microscope (SEM). Measurements showed that the
      minimum voltage for 10 nA field emission current was only 8.0 V and the maximum
      emission current density in an individual CNT emitter (1.0 nm in diameter)
      exceeded 5.7 x 10(8) A cm(-2). These results stand out in the comparison with
      recent works on individual CNT field emission, indicating that the planar devices
      based on ultra-thin individual CNTs are more competitive candidates for next
      generation electron field emitters.

PMID- 19752499
TI  - A photon position sensor consisting of single-electron circuits.
AB  - This paper proposes a solid-state sensor that can detect the position of incident
      photons with a high spatial resolution. The sensor consists of a two-dimensional
      array of single-electron oscillators, each coupled to its neighbors through
      coupling capacitors. An incident photon triggers an excitatory circular wave of
      electron tunneling in the oscillator array. The wave propagates in all directions
      to reach the periphery of the array. By measuring the arrival time of the wave at
      the periphery, we can know the position of the incident photon. The tunneling
      wave's generation, propagation, arrival at the array periphery, and the
      determination of incident photon positions are demonstrated with the results of
      Monte Carlo based computer simulations.

PMID- 19752500
TI  - Direct observation of TiO6 octahedron forming titanate nanotube by advanced
      transmission electron microscopy.
AB  - The nanostructure of titanate nanotubes known as a one-dimensional
      catalytic/electric subject is combinatorially characterized using x-ray
      diffraction (XRD), micro-Raman, photoluminescence (PL) and advanced electron
      microscopy. The micro-Raman and PL spectra prove the successful synthesis of TiO6
      octahedron units in macroscopic scale. Cryo-high-angle annular dark-field (HAADF)
      STEM and aberration-corrected (AC) TEM visualize in real-space the TiO6
      octahedron unit formed as a TiO2-based tubular structure prepared by the alkaline
      hydrothermal methods. The chirality and scrolling-up mechanism of the TiO6
      octahedron nanosheets in relation to an asymmetrical chemical environment and
      mechanical tensions are discussed.

PMID- 19752501
TI  - The mechanical response of turbostratic carbon nanotubes filled with Ga-doped
      ZnS: II. Slenderness ratio and crystalline filling effects.
AB  - Using a sample holder with an integrated force sensor, a collection of carbon
      nanotubes filled with Ga-doped ZnS, and spanning a broad window of lengths and
      diameters, has been mechanically studied inside a transmission electron
      microscope. The successful evaluation of the filled nanostructures was seen to
      depend on their slenderness ratio. Upon controlled removal of the encapsulated
      sulfide, the system considerably changed its response to uniaxial compressive
      stress. This report follows part 1 of the study which was instrument-focused and
      laid the ground to achieve consistent results with a novel type of nanomechanics
      setup for one-dimensional nanostructures (Costa et al, 2009 Nanotechnology.
      40:405706).

PMID- 19752502
TI  - A TiO2 nanostructure transformation: from ordered nanotubes to nanoparticles.
AB  - Transformation of TiO2 nanotubes (NTs) to truncated tetragonal bipyramidal shape
      nanoparticles (NPs) was observed upon thermally annealing titanium dioxide (TiO2)
      ordered nanotube arrays in fluorine ambient, resulting from the reaction of
      fluorine ions (F(-)) from the electrolyte residues in long nanotubes grown by
      anodization in ethylene glycol+NH4F electrolyte. The size of the TiO2
      nanoparticles formed depends on the fluorine concentration and can be controlled
      from 20 to 500 nm. The crystal and optical properties of the nanoparticle layers
      are superior compared with those of nanotube arrays which are also annealed but
      without undergoing a morphology transformation, as was shown by means of x-ray
      diffraction and photoluminescence spectroscopy measurements. The NT-NP
      transformation mechanism was studied by analyzing the initial stages of the NT-NP
      transformation. This was achieved by terminating the annealing process in F
      ambient after 1-5 min. It was found that amorphous NTs first contract, then break
      down, and finally merge and crystallize to form NPs.

PMID- 19752503
TI  - High-yield growth of vertically aligned carbon nanotubes on a continuously moving
      substrate.
AB  - Vertically aligned carbon nanotube (CNT) arrays are grown on a moving substrate,
      demonstrating continuous growth of nanoscale materials with long-range order. A
      cold-wall chamber with an oscillating moving platform is used to locally heat a
      silicon growth substrate coated with an Fe/Al2O3 catalyst film for CNT growth via
      chemical vapor deposition. The reactant gases are introduced over the substrate
      through a directed nozzle to attain high-yield CNT growth. Aligned multi-wall
      carbon nanotube arrays (or 'forests') with heights of approximately 1 mm are
      achieved at substrate speeds up to 2.4 mm s(-1). Arrays grown on moving
      substrates at different velocities are studied in order to identify potential
      physical limitations of repeatable and fast growth on a continuous basis. No
      significant differences are noted between static and moving growth as
      characterized by scanning electron microscopy and Raman spectroscopy, although
      overall growth height is marginally reduced at the highest substrate velocity.
      CNT arrays produced on moving substrates are also found to be comparable to those
      produced through well-characterized batch processes consistent with a base-growth
      mechanism. Growth parameters required for the moving furnace are found to differ
      only slightly from those used in a comparable batch process; thermal uniformity
      appears to be the critical parameter for achieving large-area uniform array
      growth. If the continuous-growth technology is combined with a reaction zone
      isolation scheme common in other types of processing (e.g., in the manufacture of
      carbon fibers), large-scale dense and aligned CNT arrays may be efficiently grown
      and harvested for numerous applications including providing interlayers for
      advanced composite reinforcement and improved electrical and thermal transport.

PMID- 19752504
TI  - The fabrication of periodic polymer/silver nanoparticle structures: in situ
      reduction of silver nanoparticles from precursor spatially distributed in polymer
      using holographic exposure.
AB  - A new approach to producing volume periodic polymer-metal nanoparticle structures
      is presented. Periodic distribution of Ag nanoparticles in a polymer film can be
      obtained by applying the holographic patterning in the UV or visible spectral
      range to the composite material comprising photocurable monomers, photoinitiators
      and a solution of silver nitrate in acetonitrile. Photopolymerization of the
      composite in the interference pattern provides formation of a highly efficient
      volume grating composed of periodic polymer regions and Ag precursor-containing
      regions. Subsequent homogeneous UV irradiation and/or thermo-treatment of the
      grating causes reduction of silver ions to Ag nanoparticles in the areas of the
      film containing the metal precursor. Spectroscopic measurements confirm the
      formation of the nanoparticles in the gratings. Transmission electron microscopy
      showed a regular spatial distribution of well-defined Ag nanoparticles in a
      polymer film with a periodicity governed by the geometry of holographic
      structuring. The average diameter of nanoparticles can be controlled by the
      wavelength and intensity of holographic exposure as well as the composite
      formulation. A possible mechanism of silver nanoparticle formation by free
      radicals as reducing agents is presented.

PMID- 19752505
TI  - Once-weekly administration of etanercept 50 mg improves patient-reported outcomes
      in patients with moderate-to-severe plaque psoriasis.
AB  - OBJECTIVE: To assess baseline patient-reported outcomes (PROs) and PRO
      improvement in patients with psoriasis administered etanercept 50 mg once weekly
      (QW). METHODS: Adult patients with moderate-to-severe plaque psoriasis
      participated in a 12-week, double-blind, controlled trial in which they received
      etanercept 50 mg QW (n = 96) or placebo QW (n = 46), followed by a 12-week, open
      label extension in which they received etanercept 50 mg QW (etanercept
      etanercept, n = 90; placebo-etanercept, n = 36). Patients completed the
      Dermatology Life Quality Index (DLQI), EuroQoL-5D (EQ-5D) and Functional
      Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) at baseline and
      subsequent study visits. RESULTS: At baseline, DLQI and EQ-5D scores indicated
      significant quality of life (QoL) impairment, and FACIT-F scores suggested more
      fatigue than in the general population. At week 12, etanercept 50 mg QW provided
      statistically significantly (p < 0.05) and clinically meaningfully greater
      improvement in DLQI and EQ-5D utility scores than placebo, but not in FACIT-F
      scores. After 24 weeks of etanercept, the mean DLQI suggested psoriasis had a
      small effect on QoL, while EQ-5D and FACIT-F scores were comparable to population
      norms. CONCLUSIONS: Patients with moderate-to-severe psoriasis entered this trial
      with serious PRO impairment. At week 12, etanercept 50 mg QW provided significant
      QoL improvements compared with placebo. After 24 weeks of etanercept, the
      patients' serious PRO impairment had largely abated.

PMID- 19752506
TI  - Prognostic factors in stage D heart failure in the very elderly.
AB  - BACKGROUND: The clinical characteristics of frail older patients with advanced
      heart failure have scarcely been studied. OBJECTIVE: To describe this population
      and to identify some prognostic factors of mortality. METHODS: 104 patients aged
      75 years and older hospitalized with refractory heart failure were enrolled in a
      prospective multicentric study. RESULTS: Mean age was 87.2 +/- 5.3 years. Dyspnea
      (79.8%), crepitant rales (76.9%) and peripheral edema (73.1%) were particularly
      frequent. Signs of low cardiac output such as renal insufficiency (46.9%),
      cutaneous low flow (40.4%), and systolic hypotension (< or =100 mm Hg) (24.3%)
      were observed less often. Signs of cognitive impairment including anxiety
      (55.4%), sleep disorders (43.7%) and delirium (35.5%) were frequent. Asthenia and
      chronic pain were noted in 92.3 and 37.5% of cases, respectively. Mortality rates
      were 32.7, 59.6 and 71.2% during hospitalization, at 6 months and at 12 months,
      respectively. According to the multivariate Cox model, six significant factors
      suggesting a poor prognosis were observed: chronic renal insufficiency, past
      neuropsychological pathology, long-term treatment with nitrates, presence of
      edema, low cutaneous flow, and pain. The ability to sit on a chair was the only
      significant factor associated with a good prognosis. CONCLUSION: Our study
      identified some clinical and prognostic factors which had been observed in very
      old patients with refractory heart failure. Pain management has to be a priority
      in these patients in order to improve their quality of life.

PMID- 19752507
TI  - Inflammation and anti-inflammatory strategies for Alzheimer's disease--a mini
      review.
AB  - Until recently, the central nervous system (CNS) has been thought to be an immune
      privileged organ. However, it is now understood that neuroinflammation is linked
      with the development of several CNS diseases including late-onset Alzheimer's
      disease (LOAD). The development of inflammation is a complex process involving a
      wide array of molecular interactions which in the CNS remains to be further
      characterized. The development of neuroinflammation may represent an important
      link between the early stages of LOAD and its pathological outcome. It is
      proposed that risks for LOAD, which include genetic, biological and environmental
      factors can each contribute to impairment of normal CNS regulation and function.
      The links between risk factors and the development of neuroinflammation are
      numerous and involve many complex interactions which contribute to vascular
      compromise, oxidative stress and ultimately neuroinflammation. Once this cascade
      of events is initiated, the process of neuroinflammation can become overactivated
      resulting in further cellular damage and loss of neuronal function. Additionally,
      neuroinflammation has been associated with the formation of amyloid plaques and
      neurofibrillary tangles, the pathological hallmarks of LOAD. Increased levels of
      inflammatory markers have been correlated with an advanced cognitive impairment.
      Based on this knowledge, new therapies aimed at limiting onset of
      neuroinflammation could arrest or even reverse the development of the disease.

PMID- 19752508
TI  - Noninvasive home mechanical ventilation in elderly patients.
AB  - STUDY OBJECTIVE: To determine the short- and long-term benefits of noninvasive
      home mechanical ventilation (NIHMV) in patients aged 65 and older who were
      eligible for this treatment. DESIGN AND SETTING: This retrospective, comparative,
      longitudinal study was carried out in a tertiary care hospital in Barcelona
      (Spain). PATIENTS AND METHODS: The study included all patients in whom NIHMV with
      a nasal mask was established in the period from 1998 to 2001. Patients were
      divided into 3 groups according to age: group 1 (n = 10) > or =75; group 2 (n =
      40) 65-74, and group 3 (n = 41) <65 years old. Clinical characteristics,
      pulmonary function results, and arterial blood gas findings were assessed in all
      patients before starting ventilation and after 6 months. MEASUREMENTS AND
      RESULTS: Statistically significant improvements in PaO(2) (13.4, 10, and 15.3 mm
      Hg for groups 1-3) and PaCO(2) (-17.6, -9.6 and -12.8 mm Hg for groups 1-3) were
      found at 6 months (p < 0.001 in all cases). There were no significant differences
      between the groups in blood gas parameters and treatment compliance. The
      incidence of related adverse events was not statistically different between the
      study groups (40%, 35% and 32% for groups 1-3; p = 0.859). CONCLUSIONS: NIHMV is
      effective in all patients for whom it is indicated, regardless of their age.

PMID- 19752509
TI  - Proactive and coactive interference in age-related performance in a recognition
      based operation span task.
AB  - BACKGROUND: Generally, older adults perform worse than younger adults in complex
      working memory span tasks. So far, it is unclear which processes mainly
      contribute to age-related differences in working memory span. OBJECTIVE: The aim
      of the present study was to investigate age effects and the roles of proactive
      and coactive interference in a recognition-based version of the operation span
      task. METHODS: Younger and older adults performed standard versions and
      distracter versions of the operation span task. At retrieval, participants had to
      recognize target words in word lists containing targets as well as proactive
      and/or coactive interference-related lures. RESULTS: Results show that, overall,
      younger adults outperformed older adults in the recognition of target words.
      Furthermore, analyses of error types indicate that, while younger adults were
      only affected by simultaneously presented distracter words, older adults had
      difficulties with both proactive and coactive interference. CONCLUSION: Results
      suggest that age effects in complex span tasks may not be mainly due to retrieval
      deficits in old age.

PMID- 19752510
TI  - Placental immaturity, endocardial fibroelastosis and fetal hypoxia.
AB  - We describe a term newborn who, after a normal gestational course, presented at
      birth with absent cardiac activity and no spontaneous breathing. Death occurred
      within 30 h. Autopsy revealed placental villous immaturity, multiple acute
      hypoxic lesions, but also chronic hypoxic lesions like endocardial
      fibroelastosis. This striking association of endocardial fibroelastosis and
      placental villous immaturity is reviewed and correlated with 2 other cases of
      placental villous immaturity that led to in utero death at 39 and 41 weeks of
      gestation. Placental villous immaturity must be suspected and looked for by both
      pediatricians and obstetricians in every case of stillbirth or perinatal asphyxia
      of unclear origin. In order to minimize the risk of recurrence in further
      pregnancies, elective cesarean section may be considered.

PMID- 19752511
TI  - Reverse twin-twin transfusion syndrome after fetoscopic laser photocoagulation of
      chorionic anastomoses: a case report.
AB  - A case of severe twin-twin transfusion syndrome (TTTS) which developed at
      menstrual age of 17 weeks underwent a fetoscopic laser ablation of the
      anastomosing vessels. The vascular equator of the anastomoses was noticed to be
      deviated due to marginal cord insertion of the recipient fetus. The procedure was
      accomplished uneventfully. However, the recipient fetus died 6 h after the
      procedure. After the pregnancy was terminated, the donor was found to be
      counterintuitively plethoric, and the recipient was pale. Similar appearances
      were noted on the placental territories of each fetus. This is consistent with
      reverse TTTS. Dye injection study and microscopic examination revealed a residual
      deep vein-vein anastomosis. This subchorionic vascular connection is still a
      challenge to coagulate with current placental surgery techniques. To the best of
      our knowledge, this is the first confirmed case of reverse TTTS as a cause of
      fetal loss following laser photocoagulation. This report also discusses the
      technical considerations in the complicated case of in utero placental surgery
      for TTTS.

PMID- 19752512
TI  - Ischemic ileal perforation in the donor of monochorionic twins complicated by
      twin-twin transfusion syndrome.
AB  - Twin-twin transfusion syndrome (TTTS) carries a significant risk of perinatal
      morbidity and mortality. Serial amnioreduction and fetoscopic laser
      photocoagulation have decreased perinatal mortality, thereby shifting attention
      towards short-term and long-term morbidity. Most morbidity occurs within the
      central nervous system. Ischemic lesions, however, such as congenital skin loss
      and limb necrosis may occur anywhere in the vasculature of recipient twins.
      Ischemia may also occur during serial amnioreduction and fetoscopic laser
      photocoagulation. We report a case of ileal perforation in the donor twin of
      untreated TTTS. Histopathology showed a focal area of erosion, possibly from
      ischemia. We also discuss the clinical features of ischemic intestinal
      complications of TTTS and review the literature.

PMID- 19752513
TI  - Reversed twin-to-twin transfusion syndrome following successful laser therapy.
AB  - We report a case of severe twin-to-twin transfusion syndrome (TTTS) in which
      fetoscopic laser ablation was successfully performed at 21 weeks' gestation.
      Despite successful resolution of signs on ultrasound examination after a period
      of 7 weeks, the donor developed polyhydramnios whereas the 'initial' recipient
      maintained normal liquor volume, features suggestive of 'reversed TTTS'. Two live
      babies were delivered at 31 weeks' gestation with good neonatal outcome. The
      karyotype of both babies was normal. No significant inter-twin difference in
      umbilical vein haemoglobin levels was present at delivery and placental injection
      studies did not identify persistent anastomoses. This case report supports the
      importance of close monitoring of the pregnancy following apparently successful
      laser therapy. Further research is needed to understand the pathophysiology of
      this condition.

PMID- 19752514
TI  - Heterotopic quadruplet pregnancy: conservative management with
      ultrasonographically-guided KCl injection of cornual pregnancy and laparoscopic
      operation of tubal pregnancy.
AB  - OBJECTIVE: To discuss a case of heterotopic cornual and tubal pregnancy managed
      with transvaginal potassium chloride (KCl) injection of cornual pregnancy and
      laparoscopic operation of tubal pregnancy. METHODS: The subject was a 30-year-old
      woman with twin pregnancy with a left cornual and a tubal pregnancy. The
      heterotopic cornual pregnancy was treated with ultrasonographically-guided
      transvaginal injection of KCl into the thorax of ectopic fetus, and the tubal
      pregnancy was treated with laparoscopic left salpingectomy. RESULTS: The woman
      was discharged on the 6th postoperative day. After complete ablation of the
      cornual and tubal pregnancy, the subject had no complications or side effects for
      the duration of her pregnancy up to the 37th week. Elective cesarean section was
      performed at 37 weeks and allowed the birth of 2 boys weighing 2,500 and 2,000 g
      and of normal development. CONCLUSIONS: A minimally invasive approach should be
      considered in a hemodynamically stable patient to treat a first-trimester
      heterotopic pregnancy to maintain the intrauterine pregnancy with a satisfactory
      outcome.

PMID- 19752515
TI  - Conservative management in three cases of prenatally recognized splenic cyst
      using 2D, 3D, multi-slice and Doppler ultrasonography.
AB  - The aetiology, differential diagnosis and management strategies of the foetal
      spleen affected with a cystic lesion are discussed. In the current literature,
      there are very few reports that relate to antenatally diagnosed splenic cyst. Our
      study presents 3 case reports that were first suspected due to anisoechogenic
      structures detected during routine ultrasonographic examination at the 27th, 31st
      and 34th weeks of gestation. All 3 cases were further characterized by the lack
      of pathological power Doppler findings inside and around the lesions, and were
      morphologically refined by prenatal 3D ultrasound imaging. All findings were
      reconfirmed postnatally. No complications such as cyst expansion, subcapsular
      bleeding or acute abdomen have developed, and all 3 cystic lesions have regressed
      spontaneously after birth.

PMID- 19752516
TI  - Intrauterine treatment of large fetal neck lymphangioma with OK-432.
AB  - Lymphangiomas are benign vascular malformations of the lymphatic system and most
      commonly present in the neck area. Large lymphangiomas may compress and/or
      displace the larynx, trachea and esophagus and cause serious respiratory and
      feeding problems in neonates. Prenatal therapy could eliminate the risks of the
      mentioned complications. Prenatal therapy may include the EXIT (ex utero
      intrapartum treatment) procedure. As this procedure has certain risks for both
      the neonate and mother, the introduction of a safer method is justified. The use
      of OK-432, as a sclerosing agent, has shown positive results in several published
      cases of cystic hygroma, but there is no study about the prenatal use of this
      agent in the treatment of lymphangioma. The aim of this study was to present our
      experience with intrauterine intralesional injection of OK-432 in the treatment
      of neck lymphangiomas. Two cases of large multicystic neck lymphangiomas that
      were closely situated to the fetal airway were treated by single intralesional
      injection of OK-432. We noticed a progressive decrease in tumor volume throughout
      gestation. We did not experience any complications and there were no respiratory
      or feeding problems in the neonates. The esthetical appearance was satisfactory
      and both children were normal at the age of 2 years and 6 months, respectively.
      This report suggests that prenatal intralesional injection of OK-432 might be a
      safe and effective treatment in selected cases with large fetal neck
      lymphangiomas.

PMID- 19752517
TI  - Impact of perinatal outcome of the presence of fused or separate placentas in
      dichorionic twins.
AB  - OBJECTIVE: The aim of this study was to investigate the influence of fusion of
      the placentas on various obstetric and neonatal findings in dichorionic twin
      pregnancies. METHODS: Medical charts of the total population of women who gave
      birth to dichorionic twin babies at the Japanese Red Cross Katsushika Maternity
      Hospital between 2002 and 2007 were reviewed. Data were collected from 158
      deliveries with dichorionic fused placentas and from 261 deliveries with separate
      placentas. RESULTS: There were no significant differences in various obstetric
      and neonatal findings between dichorionic twin pregnancies with fused placentas
      and those with separate placentas. CONCLUSION: The current findings indicate that
      there is no significant influence of fusion of placentas in dichorionic twin
      pregnancies.

PMID- 19752518
TI  - Prognostic role of tumor-head volume ratio in fetal sacrococcygeal teratoma.
AB  - OBJECTIVE: To evaluate the ability of a tumor-head volume ratio to predict
      outcome and incidence of hydrops in fetuses with sacrococcygeal teratoma.
      METHODS: Seventy-one sonograms were reviewed retrospectively from 28 fetuses with
      sacrococcygeal teratoma managed in our institution. Head volume (HV) and total
      tumor volume were calculated from sonograms. Amount of cystic tumor was estimated
      to determine solid tumor volume (STV) for the STV/HV ratio. RESULTS: Twenty
      percent of sonograms with STV/HV <1 and 97.3% with STV/HV >1 were associated with
      1 or more abnormal sonographic signs (p = 0.000). Overall mortality was 11/27
      (41%). There was no mortality in fetuses with a ratio of <1, while 11/18 (61%) of
      fetuses with ratio >1 died (p = 0.003). CONCLUSION: The STV/HV ratio may be used
      to identify fetuses with a high risk of a poor outcome due to high-output cardiac
      failure and hydrops, and may help guide management.

PMID- 19752519
TI  - Value of amniocentesis versus fetal tissue for cytogenetic analysis in cases of
      fetal demise.
AB  - OBJECTIVE: Use of fetal tissue for cytogenetic analysis in cases of second- and
      third-trimester fetal demise frequently results in unacceptably high failure
      rates. We reviewed our ongoing use of amniocentesis prior to uterine evacuation
      to determine if this provided a better source of cells for cytogenetic analysis.
      METHODS: We compared cytogenetic results using fetal tissues obtained following
      uterine evacuation to our ongoing use of amniotic fluid cell obtained by
      transabdominal amniocentesis prior to uterine evacuation from 2003 to 2008.
      RESULTS: In 49 of the 63 cases evaluated by fetal tissue biopsies performed after
      uterine evacuation, a karyotypic analysis was obtained (77.8%). Among the 38
      cases evaluated by amniocentesis, an amniotic fluid sample and fetal cytogenetic
      results were obtained in all 38 (100%) cases. CONCLUSION: Our findings indicate
      that amniocentesis is a more reliable source of cytogenetic information than
      fetal tissue in cases of second- and third-trimester fetal demise.

PMID- 19752520
TI  - Correct description of pentalogy of Cantrell.

PMID- 19752521
TI  - Prognosis of spina bifida in the era of prenatal diagnosis and termination of
      pregnancy.
AB  - OBJECTIVE: To evaluate the current outcome of a selected prenatally diagnosed
      spina bifida group. MATERIALS AND METHODS: We analyzed and followed up 74 cases
      of prenatally diagnosed spina bifida. RESULTS: Termination of pregnancy was
      chosen in 72% of the cases and 28% were live-born. Chromosomal defects were
      identified in 16%, although only 1.6% in isolated cases. Of the 21 live births, 3
      died in the neonatal period. The other 18 (86%) were all alive after an average
      follow-up of 3 years and 6 months (range 5 months to 7 years and 4 months). From
      this group 11% are wheelchair-dependent, 87% of the patients older than 2 years
      of age are walking, 33% have had cerebral shunting and 72% have normal
      neurodevelopment. There was a better outcome in patients with closed defects;
      however, the rates of neuropathic bladder (50%) remain a concern. CONCLUSIONS:
      Even with prenatal diagnosis and a tendency towards apparently less severe
      defects in the cases in which the pregnancies continue, the prognosis in terms of
      morbidity needs to remain guarded.

PMID- 19752522
TI  - Prenatal diagnosis of fetal cataract: case report and review of the literature.
AB  - OBJECTIVES: To report a case of prenatally diagnosed fetal cataract and conduct a
      systematic review of previously reported cases. METHODS: Review of the literature
      based mainly on Pubmed search using specific keywords in order to list cataract
      causes diagnosed prenatally and in early childhood, isolated or associated with
      microphthalmia. RESULTS AND DISCUSSION: A differential diagnosis list and
      specific prenatal diagnosis testing are suggested in order to offer the best
      management of this rare fetal condition.

PMID- 19752523
TI  - Ultrasound evaluation of the amount of Wharton's jelly and the umbilical coiling
      index.
AB  - OBJECTIVES: To investigate the association between the amount of Wharton's jelly
      (WJ) and the umbilical coiling index (UCI). METHODS: The subjects included 140
      pregnant women in the 2nd or 3rd trimester. The antenatal UCI was calculated as
      the reciprocal of the distance between a pair of coils. The sonographic cross
      sectional areas of the cord, arteries and vein were measured. The WJ area was
      calculated by subtracting areas of the total vessels from the cord. RESULTS: UCIs
      were significantly smaller and WJ areas were significantly greater in the 3rd
      trimester than in the 2nd trimester. No correlations were observed between the
      UCI and WJ area in both trimesters. CONCLUSION: There is a reduction of the UCI
      during pregnancy. No direct correlations were found between the amount of WJ and
      UCI.

PMID- 19752524
TI  - FGFR3 gene mutations in Chinese cases of thanatophoric dysplasia type 1.
AB  - OBJECTIVE: Thanatophoric dysplasia type 1 (TD 1) is typically a lethal dwarfism.
      We report our findings of fibroblast growth factor receptor 3 (FGFR3) mutations
      in Chinese cases of TD 1. METHODS: Ten cases of TD 1 were identified prenatally
      by ultrasound. The FGFR3 gene was analyzed using direct DNA sequencing of the
      selected regions (exons 7, 10, 15, and 19) previously reported to contain
      mutations for TD 1. RESULTS: A heterozygous C742T (R248C) mutation was found in 9
      of the 10 cases. The remaining case was negative for mutations involved in exons
      7, 10, 15 and 19. CONCLUSION: The results suggest that the R248C mutation may
      serve as the primarily targeted one of the FGFR3 gene for rapid molecular
      diagnosis of TD 1.

PMID- 19752525
TI  - Fetal brain hemodynamic changes in intrauterine transfusion: influence of needle
      puncture site.
AB  - OBJECTIVES: Previous research has suggested that hemodynamic changes after in
      utero transfusion may be related to fetal stress. We tested the hypothesis that
      these hemodynamic changes are more pronounced when the needle is inserted in the
      fetal abdomen compared with the umbilical cord root. METHODS: Most intrauterine
      transfusions are performed by inserting a needle either in the umbilical cord
      root at the placental surface (PCI) or in the intrahepatic portion of the
      umbilical vein (IHV). We analyzed prospectively collected data of all
      intrauterine blood transfusions (IUT) for fetal alloimmune anemia (from 2000 to
      2003), for which complete data were available on needling site and middle
      cerebral artery (MCA) Doppler flow velocity measurements before and immediately
      after the procedure. RESULTS: Data of 57 IUTs were included. In 32 patients, the
      transfusion was performed through the PCI and in 25 patients through the IHV.
      Mean pulsatility index (PI) in the PCI group was 2.0 before and 1.7 after IUT (p
      = 0.011), and in the IHV group 1.9 before and 1.5 after IUT (p = 0.001). In both
      groups, MCA PI decreased significantly, but there was no difference in decrease
      between the two groups (p = 0.99). CONCLUSIONS: In anemic fetuses undergoing
      transfusion, the observed fetal brain hemodynamic changes were independent of the
      site of needle insertion. The decrease in fetal MCA PI is therefore likely to be
      caused by the volume expansion.

PMID- 19752526
TI  - Pregnancy outcome in maternal Crigler-Najjar syndrome type II: a case report and
      systematic review of the literature.
AB  - OBJECTIVE: To report a case of maternal Crigler-Najjar syndrome (CNS) type II in
      pregnancy, systematically review the literature for similar case reports, and to
      evaluate whether pregnancy is safe in patients with the disease. Data sources
      included the PubMed and up to date databases. RESULTS: A 37-year-old mother with
      CNS type II was treated with phenobarbital during her pregnancy and her bilirubin
      levels were monitored. Her newborn had mild direct hyperbilirubinemia, did not
      require any treatment and his postnatal follow-up showed normal growth and
      development as well as normal hearing. CONCLUSION: CNS type II is rare, and only
      a few pregnancies with this condition have been reported. Maternal treatment with
      phenobarbital lowers the unconjugated bilirubin and avoids fetal and newborn
      sequelae.

PMID- 19752527
TI  - Age-related changes of anti-elastin antibodies in senescence-accelerated mice.
AB  - BACKGROUND: Antibodies recognizing the elastin precursor tropoelastin (ATEAb) or
      degradation products alpha-elastin (AEAb) are found in the serum of healthy human
      subjects, as a part of a homeostatic mechanism which assembles new or clears
      altered elastin structures. Serum ATEAb (reflecting elastin synthesis) and AEAb
      (reflecting elastin destruction) appear to correlate with the production and
      breakdown of the elastic tissue, respectively. OBJECTIVE: The aim of this study
      was to investigate plasma levels of AEAb and ATEAb in senescence-accelerated
      prone (SAMP8) and senescence-accelerated resistant (SAMR1) mice, compared with
      imprinting control region (ICR) mice in order to evaluate their age-related
      changes. METHODS: The levels of AEAb and ATEAb were measured by home-made ELISA
      in plasma of SAMP8, SAMR1, and ICR mice, grouped according to their age (3 and 9
      months) and sex. The specificity of AEAb and ATEAb activity in mouse plasma, and
      elastin-derived peptides (EDP) in sera of ICR mice at 3 and 9 months of age were
      tested by competitive ELISA. RESULTS: The specificity of AEAb and ATEAb in mouse
      plasma was confirmed by the competitive investigations. The levels of AEAb in the
      plasma of SAMR1 and SAMP8 were increased compared to the levels measured in ICR
      on the matched ages (p < 0.001). Age-related increase of the levels of AEAb and
      ATEAb was established in the 3 strains (p < 0.001). Significantly higher levels
      of AEAb were established in female 9-month-old mice compared to males in all
      strains. The ATEAb:AEAb ratio was significantly lower in the SAM compared to the
      ICR strain. Positive correlation was established between the levels of serum AEAb
      and EDP in mouse sera of ICR mice. CONCLUSION: Variations with age in the plasma
      levels of AEAb and ATEAb were established in SAM compared with ICR, and in SAMP8
      compared with SAMR1. Our findings suggest that increased anti-elastin IgG
      autoantibodies could be used as a marker of aging in SAM and possibly contribute
      to the processes of aging. The absence of a difference between SAMP8 and SAMR1
      regarding the ATEAb:AEAb ratio raises the question if SAMR1 are an appropriate
      control of SAMP8 in terms of the senescence of the elastic tissues.

PMID- 19752528
TI  - Circulating CD4+CD25 bright FOXP3+ T cells are up-regulated by biological
      therapies and correlate with the clinical response in psoriasis patients.
AB  - BACKGROUND: Regulatory T-cell (T(reg)) modulation is one of the potential
      mechanisms of anti-tumour-necrosis-factor biological agents. However, literature
      data on psoriasis patients are lacking. OBJECTIVE: To analyse the circulating
      CD4+CD25(bright)FOXP3+ subset in 30 patients with psoriasis vulgaris/arthropathic
      psoriasis treated with biologicals and to investigate its relationship with the
      clinical response. METHODS: The CD25(bright)FOXP3+ expression within the CD4+
      subset was determined by multi-parameter flow cytometry at baseline and during
      treatment. FOXP3 mRNA expression was analysed by real-time reverse transcription
      PCR. RESULTS: A response was obtained in 16/17 patients (91.1%) with increased
      CD25(bright)FOXP3+ values and in only 3/11 patients (27.3%) who showed a
      CD25(bright)FOXP3+ decrease during biological treatment (p = 0.0001). Responders
      showed significantly higher values than did non-responders as from the first 2
      months of treatment (p = 0.0032). A significantly higher posttreatment expression
      of mRNA FOXP3 was observed in responders compared to non-responders. CONCLUSION:
      Biological drugs induce a circulating T(reg) up-regulation in a significant
      percentage of patients; such an increase is an early predictive marker of
      response.

PMID- 19752529
TI  - Parathyroid hormone as a mortality predictor in frail aged inpatients.
AB  - BACKGROUND: Some prospective cohort studies have associated parathyroid hormone
      (PTH) levels with survival independently of renal function, calcaemic and vitamin
      D status in the elderly. OBJECTIVE: In order to further evaluate the prognostic
      significance of subtle elevation of PTH and the involvement of vitamin D status
      in bedridden aged inpatients, the participants of a 6-month vitamin D
      supplementation trial were followed for 2 years. METHODS: Eligible patients (n =
      218) of 4 long-term care hospitals (1,215 beds) were randomized to receive 0, 400
      or 1,200 IU/day cholecalciferol for 6 months. In addition to routine analyses,
      plasma 25-hydroxyvitamin D (25-OHD), PTH and ionized calcium (Ca(2+)) levels were
      measured. Functional capacity was evaluated by activities of daily living (ADL)
      hierarchy scale and cognition was assessed by cognitive performance scale (CPS).
      Body mass index and glomerular filtration rate (GFR) were calculated. Mortality
      data was collected from patient records. RESULTS: The patients were aged (84.5 +/
      7.5 years), vitamin D deficient (25-OHD = 23 +/- 10 nmol/l) and frail (ADL 5.5,
      range 3-6; CPS 4.9, range 1-6). The PTH levels ranged from 12 to 268 ng/l, the
      cut points for IV quartile being 72 ng/l. The PTH levels in the IV quartile
      predicted a significant 1.58-fold over-mortality (95% CI 1.08-2.32, p = 0.020),
      resulting in a 9.1-month shortening (p = 0.019) in median life expectancy in
      patients with poorest renal function, but the prognostic significance of PTH was
      not explained by GFR. Furthermore, controlling for age, gender, body mass index,
      creatinine, 25-OHD, supplementation group, Ca(2+) and albumin levels did not
      abolish this significance. Mortality was predicted neither by baseline 25-OHD nor
      vitamin D supplementation. CONCLUSIONS: Even a subtle elevation of PTH is a
      relatively independent predictor of increased 2-year mortality in severely frail
      older inpatients with poor overall survival prognosis. Further prospective
      studies on the involvement of 1,25 dihydroxyvitamin D status in the predictive
      value of PTH are needed.

PMID- 19752530
TI  - Uric acid: a novel risk factor for acute kidney injury in high-risk cardiac
      surgery patients?
AB  - BACKGROUND: Uric acid has been reported to be a risk factor for the development
      of chronic kidney disease; however, no study has examined whether uric acid may
      confer a risk for acute kidney injury. METHODS: We investigated the relation
      between serum uric acid and the incidence of postoperative acute kidney injury in
      patients undergoing high-risk cardiovascular surgery (cardiac valve and aneurysm
      surgery). RESULTS: Following cardiovascular surgery, 18 of 58 patients (31%)
      developed acute kidney injury, with 11 of 24 (45.8%) in the elevated uric acid
      group (defined as >6 mg/dl) and 7 of 34 (20.5%) in the normal uric acid group (p
      = 0.05). After controlling for baseline renal function, left ventricular ejection
      fraction, use of nesiritide, type of surgery, and history of previous surgery, an
      elevated preoperative uric acid conferred a 4-fold risk for acute kidney injury
      (OR: 3.98, CI: 1.10-14.33, p = 0.035) and longer hospital stay (36.35 vs. 24.66
      days, p = 0.009). CONCLUSION: This preliminary study suggests that uric acid may
      be a novel risk factor for acute kidney injury in patients undergoing high-risk
      cardiovascular surgery.

PMID- 19752531
TI  - Who is caring for kidney transplant patients? Variation by region, transplant
      center, and patient characteristics.
AB  - BACKGROUND/AIMS: Despite implications for long-term care, little is known about
      outpatient care for kidney transplant patients. METHODS: In this retrospective
      observational cohort study, outpatient claims were examined for 42,078 Medicare
      kidney transplant patients using United States Renal Data System data to
      ascertain location and timing of outpatient visits and type of physician seen.
      Logistic regression with generalized estimating equations was used to determine
      the odds and clinical correlates of visits in 4 post-transplant time periods.
      RESULTS: In months 1-3, 88% of patients visited their transplant centers, but
      this declined to 69% in months 25-36. In the adjusted analysis, Native Americans
      (odds ratio 0.56, 95% confidence interval 0.48-0.65) and Hispanics (OR 0.86, 95%
      CI 0.80-0.92) were less likely than whites to visit their transplant centers.
      Centers performing 18-34 (OR 1.44, 95% CI 1.30-1.59) and 35-61 transplants per
      year (OR 1.30, 95% CI 1.18-1.43) were more likely to see patients than centers
      performing <18 or >61. Almost 80% of patients saw nephrologists in months 1-3
      after transplant. African-Americans (OR 0.85, 95% CI 0.80-0.90), Asians (OR 0.87,
      95% CI 0.77-0.97), and Native Americans (OR 0.63, 95% CI 0.53-0.75) were less
      likely than whites to see nephrologists, as were Hispanics (OR 0.78, 95% CI 0.72
      0.84) compared with non-Hispanics. CONCLUSION: Frequency of visits to transplant
      centers varied by center and region; most visits were to nephrologists. Patients
      from minority groups were less likely to visit transplant centers and
      nephrologists, with possibly significant public health implications.

PMID- 19752533
TI  - Fats and fatty acids in human nutrition: introduction.

PMID- 19752532
TI  - Diverse effects of ischemic pretreatments on the long-term renal damage induced
      by ischemia-reperfusion.
AB  - BACKGROUND/AIMS: The role of ischemic pretreatment in long-term changes after
      renal ischemia-reperfusion (I/R) injury remains unknown. In this study, we mainly
      aimed to investigate the effect of ischemic pretreatments with different
      durations on the development of tubulointerstitial fibrosis and functional
      impairment following acute renal I/R. METHODS: We established a rat model of
      renal warm I/R, clamping both pedicles for 40 min followed by reperfusion; the
      experiment was followed up for 10 weeks. Prior ischemia (10, 20, 30 min) was
      induced 8 days before the 40-min ischemia. To assess tissue fibrosis, we
      performed morphometric analysis, Masson's trichrome and Sirius red staining. We
      also analyzed the expression of alpha-smooth muscle actin (alpha-SMA),
      transforming growth factor-beta(1) (TGF-beta(1)) and phospho-Smad2. RESULTS:
      Patchy tubulointerstitial fibrosis was found 5 and 10 weeks later in rats
      subjected to I/R alone or pretreated with 10-min ischemia. Tubulointerstitial
      fibrosis deteriorated further and renal dysfunction occurred in rats pretreated
      with 30-min ischemia accompanied by increased expression of alpha-SMA, TGF
      beta(1), and phospho-Smad2 at 5 weeks. In contrast, the above abnormalities were
      significantly attenuated in rats pretreated with 20-min ischemia. CONCLUSION:
      Severe I/R injury may cause tubulointerstitial fibrosis in the long term, and
      different ischemic pretreatments have diverse effects on renal fibrosis.

PMID- 19752534
TI  - Fat and fatty acid terminology, methods of analysis and fat digestion and
      metabolism: a background review paper.

PMID- 19752535
TI  - Review of fat and fatty acid requirements and criteria for developing dietary
      guidelines.

PMID- 19752536
TI  - Fats and fatty acid requirements for adults.

PMID- 19752537
TI  - Fat and fatty acid requirements and recommendations for infants of 0-2 years and
      children of 2-18 years.

PMID- 19752538
TI  - Background paper on fat and fatty acid requirements during pregnancy and
      lactation.

PMID- 19752539
TI  - Effects of fat and fatty acid intake on inflammatory and immune responses: a
      critical review.

PMID- 19752540
TI  - Background review paper on total fat, fatty acid intake and cancers.

PMID- 19752541
TI  - Fat and fatty acid intake and metabolic effects in the human body.

PMID- 19752542
TI  - Dietary fat and coronary heart disease: summary of evidence from prospective
      cohort and randomised controlled trials.

PMID- 19752543
TI  - Fat intake and CNS functioning: ageing and disease.

PMID- 19752544
TI  - The relationship between dietary fat and fatty acid intake and body weight,
      diabetes, and the metabolic syndrome.

PMID- 19752545
TI  - Background paper on global trends in food production, intake and composition.

PMID- 19752546
TI  - Processing, manufacturing, uses and labelling of fats in the food supply.

PMID- 19752547
TI  - Oxygen-ozone therapy in medicine: an update.
AB  - Oxygen-ozone therapy, initially started as an empirical approach, has now reached
      a stage where most of the biological mechanisms of action of ozone have been
      clarified, showing that they are in the realm of orthodox biochemistry,
      physiology and pharmacology. Here we have reviewed a few relevant clinical
      applications and have shown that ozone therapy is particularly useful in
      cardiovascular disorders and tissue ischemia. In chronic viral infections, it is
      unable to eliminate the viremia but it may display supportive help by stimulating
      the immune system. Recently, its use has been successfully extended to the
      herniated disk pathology and therapy of primary caries in children.

PMID- 19752548
TI  - Burden and perceived health status among caregivers of stroke patients.
AB  - OBJECTIVE: To identify the main determinants of burden and perceived health
      status in caregivers of Brazilian stroke survivors. METHODS: Cross-sectional
      study. Caregivers answered the Hospital Anxiety and Depression Scale (HADS),
      Zarit caregiver burden interview (ZCBI) and EuroQol. Patients were assessed with
      the National Institute of Health Stroke Scale, Barthel index (BI), modified
      Rankin scale (m-RS), Mini Mental State Examination and HADS. RESULTS: 200
      caregiver-patient dyads were assessed. Caregivers were significantly younger (42
      vs. 57.7 years) and had more years of formal education (10 vs. 7.8 years); p <
      0.0001. Seventy-seven percent of caregivers were females, and 41% were spouses.
      The prevalence of anxiety disorders was significantly higher in female caregivers
      than in males (26.1 vs. 10.9%; p = 0.04). ZCBI mean score was 27.2, and female
      caregivers had significantly worse scores (28.7 vs. 22.3, p = 0.003). ZCBI mean
      score significantly increased (worsened) as the severity of the disease, based on
      m-RS, increased. ZCBI mean scores were significantly higher in wives than in
      other relatives (31.4 vs. 22.6; ANOVA, p < 0.0001). The EuroQol-5D and EuroQol
      Visual Analog Scale mean scores were 0.7 (range: 0.04-0.85) and 75.2 (range: 1
      100), respectively. Adequate convergent validity (r = -0.38 to -0.40) between
      EuroQol and ZBCI mean scores was observed. Patient s disability (as measured by
      the BI) and caregiver's factors (female sex, depression as measured by HADS
      depression) were independent predictors of caregiver's burden (r2 adjusted =
      0.48; p < 0.0001) in the multivariate regression analysis. CONCLUSIONS:
      Caregiver's mood was the most consistent factor influencing caregiver burden and
      perceived health in stroke caregivers.

PMID- 19752549
TI  - Computed tomographic angiography: diagnostic procedure of choice in the
      management of subarachnoid hemorrhage in the elderly patient?
AB  - BACKGROUND: The objective of this study was to establish whether 3D computed
      tomographic angiography (CTA) can be used to determine further management in
      patients older than 70 years admitted with acute subarachnoid hemorrhage (SAH).
      PATIENTS AND METHODS: CTA evaluation included analysis of the source images,
      image-slice-based multiplanar reconstruction, multi-intensity projection (MIP)
      and finally 3-dimensional rendering. The location and size of the aneurysm, its
      precise anatomical morphology and the configuration of the circle of Willis were
      evaluated. Based on these findings, surgery, endovascular coiling or conservative
      management was selected. RESULTS: Between October 2001 and June 2005, 44 patients
      over 70 years of age (38 females, 6 males) were admitted to our neurosurgical
      department with acute SAH. All patients underwent CTA, and additional 2D digital
      subtraction angiography (2D-DSA) was performed in 14 patients. Forty-five
      aneurysms (38 ruptured and 7 unruptured) were diagnosed. Six patients were found
      to have SAH of unknown origin (no aneurysm on CTA nor 2D-DSA). In 20 patients
      surgery was performed, in 10 patients endovascular coiling of the aneurysm was
      carried out, and 12 patients were treated conservatively. The findings on CTA and
      2D-DSA could be compared for 26 patients (59%). Correlation between CTA and 2D
      DSA was good in 25 of these cases (96%). Glasgow Outcome Scale scores of 4 or 5
      were calculated for 37% of the operated patients, 27% of those treated with
      coils, and 36% of the patients treated conservatively. CONCLUSION: In older
      patients with degenerative vascular diseases, CTA can replace 2D-DSA in most
      cases if the image quality is excellent and analysis is performed carefully.

PMID- 19752550
TI  - Impaired function of innate T lymphocytes and NK cells in the acute phase of
      ischemic stroke.
AB  - BACKGROUND: Functional alterations of innate lymphocytes, which can mount rapid
      immune responses and shape subsequent T cell reactions, were examined in the
      acute phase of ischemic stroke. METHODS: Frequencies, intracellular perforin and
      interferon-gamma (IFN-gamma) expression of Vdelta2 T cells, CD3+ CD56+ natural
      killer T (NKT)-like and NK cells were examined in the peripheral blood of 20
      healthy controls and 28 patients within 6 h of the onset of acute ischemic stroke
      and after 72 h by flow cytometry. Cytokine production of isolated NKT-like and NK
      cells following in vitro activation was measured by cytometric bead array. NK
      cytotoxicity was examined in the peripheral blood mononuclear cells. RESULTS:
      Percentages of Vdelta2, NKT-like and NK cells were constant, and similar to
      percentages in healthy subjects. In contrast, proinflammatory intracellularIFN
      gamma expression by Vdelta2 T cells, NKT-like cells and NK cells and IFN-gamma
      production by isolated NK cells in culture was low at 6 h and reached the level
      of healthy subjects by 72 h after stroke. Production of anti-inflammatory
      cytokines was unaltered. Intracellular perforin expression by Vdelta2 T cells,
      NKT-like cells and NK cells, and NK cytotoxicity was low at 6 h, and reached the
      level of healthy subjects by 72 h. Increases in IFN-gamma and perforin expression
      by Vdelta2 T cells correlated with clinical improvement indicated by decreases in
      NIHSS scores. CONCLUSIONS: Pro-inflammatory and cytotoxic responses of NK, NKT
      like and Vdelta2 T cells become acutely deficient in ischemic stroke, which may
      contribute to an increased susceptibility to infections.

PMID- 19752551
TI  - Polymorphisms associated with both noncardioembolic stroke and coronary heart
      disease: vienna stroke registry.
AB  - Noncardioembolic stroke and coronary heart disease (CHD) may share genetic
      predispositions. We tested the hypothesis that genetic variants which are
      associated with risk of CHD would also be associated with risk of
      noncardioembolic stroke in 562 cases from the Vienna Stroke Registry and 815
      controls. We selected 6 gene variants that had been consistently associated with
      risk of CHD in 3 studies, including the Atherosclerosis Risk in Communities
      study, and found that 4 of these gene variants were also associated with risk of
      noncardioembolic stroke. The odds ratios for noncardioembolic stroke were 1.31
      (90% CI 1.07-1.60) for rs3900940 in MYH15, 1.24 (90% CI 1.01-1.5) for rs20455 in
      KIF6, 1.21 (90% CI 0.99-1.49) for rs1010 in VAMP8, and 1.20 (90% CI 0.95-1.50)
      for rs10757274 on chromosome 9p21.

PMID- 19752552
TI  - Effect of the thromboxane prostaglandin receptor antagonist terutroban on
      arterial thrombogenesis after repeated administration in patients treated for the
      prevention of ischemic stroke.
AB  - BACKGROUND: The antithrombotic, antiplatelet and endothelial activity of
      terutroban, a specific thromboxane prostaglandin receptor antagonist, was
      assessed in patients previously treated with aspirin for the prevention of
      ischemic stroke. METHODS: This double-blind, parallel-group, 10-day study
      included 48 patients (age = 70.5 +/- 9.5 years) with cerebral ischemic event
      and/or carotid stenosis in 4 groups: terutroban 10 mg/day (n = 13), aspirin 300
      mg/day (n = 12), terutroban 10 mg/day + aspirin 300 mg/day (n = 11) or
      clopidogrel 75 mg/day + aspirin 300 mg/day (n = 12). The measurements included
      parameters from an ex vivo model of thrombosis, platelet aggregation in platelet
      rich plasma and plasma biomarkers of endothelial/platelet activation. RESULTS:
      Between days 0 and 10, the mean cross-sectional surface of dense thrombus
      significantly decreased with terutroban (58%, p = 0.001), terutroban + aspirin
      (63%, p = 0.005) and clopidogrel + aspirin (61%, p < 0.05). On day 10, the value
      for terutroban was significantly lower than that for aspirin (p < 0.01) and was
      comparable to the dual therapy terutroban + aspirin or clopidogrel + aspirin.
      Similar results were found for total thrombus surface and platelet adhesion.
      Platelet aggregation induced by the specific thromboxane prostaglandin receptor
      agonist U46619 was almost completely inhibited on day 10 in both terutroban
      groups but not in the others. As regards markers of endothelial/platelet
      activation or lesions, thrombomodulin significantly increased and plasma soluble
      P selectin significantly decreased by day 10 in both terutroban groups, whereas
      the von Willebrand factor did not change significantly. Terutroban was found to
      be safe and well TOLERATED. CONCLUSIONS: Terutroban has demonstrated an
      antithrombotic activity that is superior to aspirin and similar to clopidogrel +
      aspirin; it induces a significant in vivo reduction in endothelial/platelet
      activation.

PMID- 19752553
TI  - NFKB1 -94 insertion/deletion ATTG polymorphism in gastroenteropancreatic
      neuroendocrine tumors.
AB  - Nuclear factor-kappaB (NF-kappaB) is a transcription factor responsible for
      modulating the expression of many genes involved in immune response, inflammatory
      process, cell growth and survival. A functional and common promoter polymorphism
      of the NF-kappaB1 (NFKB1) gene leads to alteration in the activation pattern and
      expression of NF-kappaB, and thus, is probably associated with carcinogenesis.
      The aim of this study was to detect the importance and the frequency of NFKB1 -94
      insertion/deletion ATTG promoter polymorphism in patients with
      gastroenteropancreatic neuroendocrine tumor. A case-control cohort including 50
      patients with gastroenteropancreatic neuroendocrine tumor and 100 healthy
      controls was genotyped with the polymerase chain reaction method. Polymerase
      chain reaction products were analyzed in agarose gel electrophoresis and
      processed with the Van91I restriction enzyme. There are 2 cleavage points on the
      amplified region. When ATTG insertion or deletion is present, the function of
      restriction enzyme changes. Thirty patients (60%) had ID (insertion/deletion), 18
      (36%) had II (insertion/insertion) and 2 (4%) had DD (deletion/deletion)
      genotypes. Fifty-eight of the control group (58%) had ID, 30 (30%) had II and 12
      (12%) had DD genotypes. The frequencies of D and I alleles were 34 and 66 in the
      study group, and 82 and 118 in the control group, respectively. Although the
      frequencies of I and D alleles and genotype distribution did not differ between
      the study and control groups, there seem to be important differences concerning
      the DD genotype analyses of the NFKB1 -94ins/delATTG promoter polymorphism
      between patients with pancreatic neuroendocrine tumor and those with carcinoid
      tumor. This may support the view that the genetics of carcinoid tumors and
      pancreatic neuroendocrine tumors are different and should be further studied.

PMID- 19752554
TI  - A case of pulmonary lymphomatoid granulomatosis successfully treated by
      combination chemotherapy with rituximab.
AB  - Lymphomatoid granulomatosis (LYG) is a rare angiocentric and angiodestructive
      lymphoproliferative disease characterized by Epstein-Barr virus-positive B cells
      admixed with reactive T cells. LYG most commonly affects the lung but can also
      involve other extrapulmonary sites. Pulmonary LYG usually presents as multiple
      pulmonary nodules with rapid progression and excavation. It can mimic various
      infectious diseases, vasculitis or metastatic malignancy and is difficult to be
      diagnosed clinically. Standard treatment for LYG has not yet been established.
      Despite combination chemotherapy, the overall prognosis is poor. Recently, anti
      CD20 monoclonal antibody, rituximab, has been used to treat LYG. We report the
      case of a 70-year-old male patient with pulmonary LYG, who showed rapid remission
      of the disease after combination chemotherapy with rituximab.

PMID- 19752555
TI  - Validity and reliability of the SF-36 administered to caregivers of patients with
      alzheimer's disease: evidence from a south american sample.
AB  - BACKGROUND: Being a caregiver of a patient with Alzheimer's disease is associated
      with impaired health status and declines in health-related quality of life
      (HRQoL). This paper evaluates the reliability and validity of the Argentinean
      version of the Medical Outcomes Study Short-Form Health Survey (SF-36) among
      caregivers of patients with Alzheimer's disease. METHODS: Forty-eight caregivers
      of Alzheimer's disease patients completed the SF-36, the Zarit Burden Interview
      (ZBI) and the Neuropsychiatric Inventory (NPI). Patients were evaluated for
      dementia severity using the Clinical Dementia Rating (CDR) and for cognitive
      status using the Mini Mental State Examination (MMSE). RESULTS: The SF-36 scales
      demonstrated adequate-to-strong internal consistency (Cronbach's alpha range:
      0.72 to 0.92). Correlations between the SF-36 scales and the ZBI were moderate to
      strong (range: -0.19 to -0.79, all p < 0.01 expect for physical function).
      Significant correlations between the SF-36 scales and the CDR, MMSE and NPI were
      lower (range: -0.30 to -0.40, p < 0.001) and strongest in mental health-related
      scales of the SF-36. The SF-36 demonstrated good factorial validity. CONCLUSIONS:
      The Argentinean translation of the SF-36 is reliable and valid for use to measure
      the HRQoL of caregivers of patients with Alzheimer's disease.

PMID- 19752556
TI  - Low diastolic pressure and risk of dementia in very old people: a longitudinal
      study.
AB  - BACKGROUND/AIM: Midlife high blood pressure is linked to late-life dementia. We
      sought to investigate the temporal relation of blood pressure to the risk of
      dementia and Alzhei-mer's disease (AD) among older adults. METHODS: A dementia
      free cohort (n = 422) aged > or =81 years was followed for 3 years to detect
      dementia and AD cases (Diagnostic and Statistical Manual of Mental Disorders,
      Third Edition, Revised criteria). The blood pressure was measured 4 times over a
      9-year period starting from > or =75 years of age. The data were analyzed with
      Cox models controlling for potential confounders. RESULTS: During the 954 person
      years of follow- up, 89 subjects developed dementia (72 AD cases). Low diastolic
      pressure (<70 vs. 70-89 mm Hg) was associated with a multiadjusted hazard ratio
      of 2.13 [95% confidence interval (CI) = 1.05-4.32] for dementia and 2.16 (95% CI
      = 0.98-4.73) for AD occurring over a 6-to 9-year period, whereas high diastolic
      pressure (> or =90 mm Hg) was marginally related to a decreased hazard ratio of
      0.58 (95% CI = 0.33-1.02) for dementia and 0.57 (95% CI = 0.30-1.09) for AD.
      Systolic pressure was not significantly related to dementia risk. Subjects who
      developed dementia had a greater decline in blood pressure than persons who did
      not, mainly during the 3-year period before dementia diagnosis. CONCLUSION: Low
      diastolic pressure predicts the risk of dementia among very old people, and the
      blood pressure exhibits a substantial decline over around 3 years before the
      dementia syndrome becomes clinically evident.

PMID- 19752557
TI  - Multiple gene status in Helicobacter pylori strains and risk of gastric cancer
      development.
AB  - BACKGROUND/AIM: The identification of the vacA intermediate region has provided
      new insights into the role of vacA heterogeneity in relation to gastro-duodenal
      pathogenesis. The aim of this study was to assess vacA polymorphism in Iranian
      Helicobacter pylori strains and its association with cagA as a major virulence
      determinant, gastric histopathology and disease. METHODS: vacA polymorphism and
      serum antibody responses were studied in 207 H. pylori-infected (139 NUD, 34 PUD,
      and 34 GC) patients and correlated with gastric histopathology. RESULTS:
      Multivariate logistic regression analysis found intermediate region typing
      superior to signal or mid region typing for screening high risk patients. vacA i1
      allele was identified as an independent predictor of dysplasia (OR = 9.044; 95%
      CI: 1.11-73.33). Possession of s1/i1/cagA(+) strains was also identified as a
      predictor of intestinal metaplasia (OR = 3; 95% CI: 1.13-7.95), dysplasia (OR =
      9.9; 95% CI: 1.23-80.86) and risk of GC (OR = 6.9; 95% CI: 2.5-18.66) as well as
      induction of anti-VacA sero-positivity (OR = 5.04; 95% CI: 1.8-13.6). Anti-VacA
      serology correctly detected 83.8% of s1/i1/cagA(+) strains carried by high-risk
      patients. CONCLUSIONS: The current study emphasizes the implication of vacA
      polymorphic structure, especially the s1/i1/cagA(+) genotype, in increasing the
      risk of GC by revealing their association with gastric pre-neoplastic changes and
      their reflection in VacA sero-positivity which encourages the application of
      noninvasive procedures in population screening.

PMID- 19752558
TI  - Fatigue is not associated with impaired function of regulatory T cells in
      untreated patients with multiple sclerosis.
AB  - BACKGROUND: The pathophysiology of multiple sclerosis (MS)-associated fatigue is
      poorly understood. Immunological mechanisms may play a role. Alterations in
      immunological profile indicate a chronic immune activation in MS patients with
      fatigue. T-regulatory (Treg) cells seem to play a key role in coordinating
      autoimmune mechanisms in MS. This is the first study investigating the
      relationship between Treg cell function and fatigue in MS patients. METHODS: In
      this cross-sectional in vitro, ex vivo study, we isolated peripheral blood
      mononuclear cells (PBMCs) from 20 MS patients with fatigue, determined lymphocyte
      subsets by flow cytometry and suppressive function of Treg cells in PBMC cultures
      with antigen stimulation. Forkhead box protein 3 expression was evaluated by PCR.
      Results were compared with 20 MS patients without fatigue and with 19 healthy
      controls. RESULTS: Leukocytes and lymphocyte subsets including Treg cell
      frequency did not differ in patients with and without fatigue. Co-culturing of
      Treg cells with CD4+CD25- cells did not lead to a significant suppression of
      myelin basic protein- and pokeweed mitogen-induced proliferation in MS patients
      in contrast to healthy controls. There were no statistical differences between MS
      patients with and without fatigue regarding this suppression activity.
      CONCLUSIONS: Fatigue seems not to be associated with impaired function of Treg
      cells in untreated MS patients.

PMID- 19752559
TI  - Untired regulatory T cells: untying fatigue from T cell regulation in multiple
      sclerosis.

PMID- 19752560
TI  - Transcriptome-wide characterization of gene expression associated with unruptured
      intracranial aneurysms.
AB  - BACKGROUND: The biological mechanisms by which cerebral aneurysms emerge, enlarge
      and rupture are not totally understood. In the present study, we analyzed the
      genome-wide gene expression profile in human intracranial aneurysms using cDNA
      microarrays. METHODS: Affymetrix HU133 Plus 2.0 microarrays were used to compare
      gene expression levels between human cerebral aneurismal samples and normal blood
      vessels. Raw data were evaluated by GeneSpring software version 9.05.
      Differentially expressed genes were further classified according to the Gene
      Ontology and Kyoto Encyclopedia of Genes and Genomes annotations. Quantitative
      real-time polymerase chain reaction was used to confirm the microarray results.
      RESULTS: Clustering analysis demonstrated that the aneurysm tissues and control
      tissues were clearly separated into two distinct groups according the
      differential expression patterns. The levels of 1,160 genes were significantly
      changed. Of these genes, 164 were upregulated and 996 were downregulated. A
      cluster of extracellular matrix related genes, including collagens (type I, III,
      V, and XI) and metalloproteinases were significantly upregulated. In contrast to
      previous reports, we found that a number of immune/inflammation-related genes
      were downregulated in intracranial aneurysms. CONCLUSION: Human cerebral
      aneurysms appeared to show a similarity in the global gene expression profile.
      Our results support the notion that disrupted homeostasis of the extracellular
      matrix components may be involved in the pathogenesis of intracranial aneurysms.
      Our data of the differentially regulated genes may benefit future studies on the
      cellular mechanisms of cerebral aneurysms.

PMID- 19752561
TI  - Retrospective evaluation of CO(2) laser conization in pregnant women with
      carcinoma in situ or microinvasive carcinoma.
AB  - BACKGROUND: We evaluated the safety and efficacy of CO(2) laser conization in
      pregnant women with cervical intraepithelial neoplasia 3/carcinoma in situ
      (CIN3/CIS) or microinvasive carcinoma (MIC). OBJECTIVES: A total of 49 pregnant
      women with biopsy-proven CIN3/CIS (30 patients) or MIC (19 patients) were
      studied. METHODS: Retrospective analysis based on clinical records. RESULTS:
      Median age and median week of gestation were 31 years (range: 22-39) and 17 weeks
      (range: 7-33), respectively. The median length of cervix resected by conization,
      median duration of surgery and median blood loss were 14 mm (range: 5-23), 20 min
      (range: 7-35) and 78 ml (range: 10-797), respectively. One biopsy-proven CIN3/CIS
      patient was diagnosed with Federation of Gynecology and Obstetrics (FIGO) Ia2 and
      3 biopsy-proven MIC patients were diagnosed with FIGO Ib1 based on conization
      specimens. A total of 35 patients could be followed until delivery, of which 27
      (77.1%) patients delivered transvaginally. Although 8 patients (22.9%) had a
      cesarean section and 6 patients (17.1%) delivered preterm, no conization-related
      obstetric complications were observed. CONCLUSION: Since it results in few
      obstetric complications, CO(2) laser conization within 20 mm of length can be
      considered a safe procedure for pregnant women.

PMID- 19752562
TI  - Mast cells and basophils: a potential link in promoting angiogenesis during
      allergic inflammation.
AB  - Mast cells and basophils are granulated metachromatic cells which possess complex
      and partially overlapping roles in acquired and innate immunity, including both
      effector and regulatory activities. Mast cells and basophils cooperate in
      exacerbating and/or modulating inflammation as well as in mediating subsequent
      tissue repair. Mast cells release a series of potent proangiogenic molecules
      during inflammation that stimulate vessel sprouting and new vessel formation.
      Recent data suggest that basophils may also play a role in inflammation-related
      angiogenesis, principally but not exclusively through the expression of several
      forms of vascular endothelial growth factors and their receptors. This review
      focuses on the potential cooperative link between mast cells and basophils in
      promoting angiogenesis during allergic inflammation. We discuss the multifaceted
      roles of mast cells and basophils in inflammatory mechanisms of allergic diseases
      and whether these cells can be both source and target of proangiogenic mediators.

PMID- 19752563
TI  - The traditional herbal medicine saireito exerts its inhibitory effect on murine
      oxazolone-induced colitis via the induction of Th1-polarized immune responses in
      the mucosal immune system of the colon.
AB  - BACKGROUND: Ulcerative colitis is an intractable inflammatory colonic disease,
      and its etiology remains unclear. Saireito, a traditional herbal medicine, is
      widely used for treating ulcerative colitis in Japan. We analyzed the
      immunological characteristics of an oxazolone (OXZ)-induced colitis (OC) model
      and examined the effects of sareito on this model. METHODS: OXZ was injected into
      the colon of BALB/c mice. Saireito was orally administered once a day for 3
      consecutive days. Colitis was assessed by scoring the symptoms and macroscopic
      findings. The transcription patterns in the middle colon and spleen were analyzed
      with global transcriptome analysis and real-time polymerase chain reaction (PCR).
      RESULTS: The above-mentioned scores were increased in the OC mice. The
      transcription levels of Th2 cytokines were significantly upregulated in the
      spleen and middle colon of the OC mice, whereas those of the Th1 cytokine
      interferon (IFN)-gamma decreased in the spleen and increased in the middle colon.
      Saireito significantly ameliorated OC. In the middle colon of the saireito
      treated mice, enhanced expression of Th2 cytokine mRNAs was markedly
      downregulated, while that of IFN-gamma mRNA was further upregulated. In contrast,
      in the spleen, saireito had no effect on the transcription of either type of
      cytokine. After global transcriptome analysis, real-time PCR analysis revealed
      that saireito greatly downregulated the enhanced expression of the suppressor of
      cytokine signaling (SOCS)-3 mRNA in the middle colon of OC mice. CONCLUSIONS:
      Saireito exhibits inhibitory effects on OC by the induction of Th1-polarized
      immune responses in the mucosal immune system of the colon.

PMID- 19752564
TI  - Oral treatment with probiotics reduces allergic symptoms in ovalbumin-sensitized
      mice: a bacterial strain comparative study.
AB  - BACKGROUND/AIM: Evidence demonstrating an important role of the intestinal
      microbiota in the incidence of allergic disorders has led to the concept of using
      probiotics as possible antiallergic therapy. This study aimed to select a
      bacterial strain with the best antiallergic treatment effects from a panel of 6
      bacterial strains in a mouse model of ovalbumin(OVA)-allergic asthma. METHODS:
      OVA-sensitized BALB/c mice were orally administered the bacterial strains
      Bifidobacterium breve M-16V, B. infantis NumRes251, B. animalis NumRes252 and
      NumRes253, Lactobacillus plantarum NumRes8 and L. rhamnosus NumRes6. After
      challenge by OVA inhalation in the lungs, the response to methacholine was
      measured. Pulmonary inflammation was assessed by analyzing bronchoalveolar lavage
      fluid for the presence of eosinophils, neutrophils, macrophages and lymphocytes
      and for interleukin 4, interleukin 5, interleukin 10 and interferon-gamma. OVA
      specific IgE, IgG1 and IgG2a were measured in serum. Next, the effect on acute
      allergic skin reaction was measured after treatment with B. breve M-16V and L.
      plantarum NumRes8. RESULTS: Of the panel of 6 strains, B. breve M-16V and L.
      plantarum NumRes8 inhibited (1) the response to methacholine, (2) reduced the
      number of eosinophils in the bronchoalveolar lavage fluid, (3) reduced both OVA
      specific IgE and (4) OVA-specific IgG1, whereas the other strains did not affect
      all these parameters simultaneously. B. breve M-16V but not L. plantarum NumRes8
      reduced interleukin 4, interleukin 5 and interleukin 10. Furthermore, B. breve M
      16V but not L. plantarum NumRes8 reduced acute allergic skin reactions to OVA.
      CONCLUSION: B. breve M-16V was identified as the most potent antiallergic strain.

PMID- 19752565
TI  - TLR3 in human eosinophils: functional effects and decreased expression during
      allergic rhinitis.
AB  - BACKGROUND/AIM: Viral respiratory infections are increasingly implicated in
      allergic exacerbations. Virus-induced activation of eosinophils through Toll-like
      receptors (TLRs) could be involved. The present study was designed to examine
      TLR3 expression in eosinophils from bone marrow (BM) and peripheral blood (PB)
      during symptomatic allergic rhinitis, and to evaluate the functional
      responsiveness of TLR3 in purified eosinophils. METHODS: BM and PB samples were
      obtained from healthy volunteers and patients with seasonal allergic rhinitis
      outside and during the pollen season. Eosinophils were analyzed for TLR3
      expression by flow cytometry. Polyinosinic:polycytidylic acid [poly(I:C)], an
      agonist for TLR3, was used to assess its functional role in purified eosinophils
      and the intracellular signaling pathways involved. RESULTS: TLR3 expression was
      demonstrated in BM and PB eosinophils. It was higher in BM-derived than in
      circulating cells and it was downregulated in both compartments during
      symptomatic allergic rhinitis. TLR3 expression was also downregulated in the
      presence of interleukin (IL)-4 and IL- 5. Stimulation with poly(I:C) increased
      the percentage of CD11b+ cells and enhanced the secretion of IL-8, effects
      mediated via the p38 mitogen-activated protein kinases and nuclear factor-kappaB
      signaling pathways. Moreover, pretreatment with IL-5 augmented the poly(I:C)
      induced IL-8 release. CONCLUSIONS: Eosinophils activated via TLR3 might be more
      able to home and recruit leukocytes to sites of inflammation. The decreased TLR3
      expression during symptomatic allergic rhinitis and in the presence of Th2
      cytokines indicates a role in allergic airway inflammation. Thus, eosinophils
      might function as a link between viral infections and exacerbations of allergic
      disease.

PMID- 19752566
TI  - Participation of CD11b and F4/80 molecules in the conjunctival eosinophilia of
      experimental allergic conjunctivitis.
AB  - BACKGROUND: CD11b and F4/80 are macrophage surface markers. How these molecules
      participate in allergic eosinophil infiltration remains unclear. We examined the
      roles CD11b and F4/80 play in the conjunctival eosinophil infiltration associated
      with experimental allergic conjunctivitis. METHODS: Ragweed-immunized BALB/c mice
      were challenged with ragweed in eye drops to induce conjunctival eosinophil
      infiltration. The effect of challenge on conjunctival CD11b+ and F4/80+ cell
      numbers was determined by immunohistochemistry. In the same model, blocking anti
      CD11b and anti-F4/80 Abs were injected intraperitoneally during the induction or
      the effector phase, or subconjunctivally 2 h before challenge, to determine their
      effect on challenge-induced conjunctival eosinophilia. To examine whether
      eosinophils express CD11b and F4/80 molecules, splenocytes from IL-5 gene
      electroporated mice were subjected to flow cytometric analysis. To clarify the
      involvement of CD11b and F4/80 in conjunctival eosinophil infiltration, mice were
      intraperitoneally injected with anti-CD11b and anti-F4/80 Abs and then
      subconjunctivally injected with eotaxin to induce conjunctival eosinophilia.
      RESULTS: Ragweed challenge elevated conjunctival CD11b+ and F4/80+ cell numbers.
      Systemic anti-CD11b and anti-F4/80 Ab treatments during the effector phase, but
      not in either the induction phase or the local injection of Ab, suppressed
      conjunctival eosinophil infiltration in ragweed-induced conjunctivitis. Most
      splenic eosinophils from IL-5 gene-introduced mice expressed CD11b and F4/80.
      Systemic anti-CD11b and anti-F4/80 Ab treatment suppressed conjunctival
      eosinophilia induced by subconjunctival eotaxin injection. CONCLUSIONS: CD11b and
      F4/80 appear to participate in conjunctival eosinophil infiltration in allergic
      conjunctivitis. Their involvement in conjunctival eosinophilia appears to be due
      to their expression on eosinophils rather than on macrophages.

PMID- 19752567
TI  - Nasal lavage in pregnant women with seasonal allergic rhinitis: a randomized
      study.
AB  - BACKGROUND: Nasal rinsing appears particularly suitable in the management of
      pregnant women with seasonal allergic rhinitis since no deleterious effects on
      the fetus are to be expected. However, to date, no studies have specifically
      investigated this option. METHODS: Pregnant women with seasonal allergic rhinitis
      were randomized to intranasal lavage with hypertonic saline solution 3 times
      daily (n = 22) versus no local therapy (n = 23) during a 6-week period
      corresponding to the pollen season. Patients were invited to keep a daily record
      of rhinitis symptoms (rhinorrea, obstruction, nasal itching and sneezing), to
      record consumption of oral antihistamine and to undergo rhinomanometry. RESULTS:
      The rhinitis score was similar at study entry but a statistically significant
      improvement in this score was observed in the study group during all subsequent
      weeks (p < 0.001 for weeks 2-6). The mean number of daily antihistamines use per
      patient per week was significantly reduced at weeks 2, 3 and 6 (p < 0.001, p <
      0.001 and p = 0.001, respectively). Baseline rhinomanometry performed at week 1
      showed similar nasal resistance in the study and control groups. In contrast, a
      statistically significant difference emerged in the 2 following evaluations. At
      week 3, nasal resistance in the study and control groups was 0.96 +/- 0.44 and
      1.38 +/- 0.52 Pa/ml/s, respectively (p = 0.006). At week 6, it was 0.94 +/- 0.38
      and 1.35 +/- 0.60 Pa/ml/s, respectively (p = 0.006). No adverse effect was
      reported in the active group. CONCLUSIONS: Nasal rinsing is a safe and effective
      treatment option in pregnant women with seasonal allergic rhinitis.

PMID- 19752568
TI  - Incidence and remission of specific IgE aeroallergen sensitization from age of 40
      to 60 years, and association with alcohol consumption.
AB  - BACKGROUND: Data on incidence and long-term persistence of IgE aeroallergen
      sensitization in older adults are limited. Alcohol consumption is a strong immune
      modulator with a significant impact on the IgE response. OBJECTIVES: We aimed to
      assess the incidence and remission of aeroallergen sensitization from the age of
      40 to 60 years. Furthermore, we examined the relationship of alcohol consumption
      to the prevalence and incidence of aeroallergen sensitization. METHODS: In 1976
      1977, a total of 1,200 people born in 1936 and randomly selected from the general
      population were invited for a health examination (1,052 were examined). At 60
      years, they were invited for a re-examination (695 were examined). Stored serum
      samples from both examinations were analyzed consecutively for serum-specific IgE
      to aeroallergens by using a qualitative multi-allergen immunoassay. RESULTS: We
      observed a total of 32 (7.1% of those not sensitized at 40 years) incident cases
      and 35 (41.1% of those sensitized at 40 years) remittent cases of aeroallergen
      sensitization over this 20 year period. Persistent as well as incident
      sensitization was significantly associated with self-reported atopic disease at
      60 years. Alcohol consumption (>14 drinks per week) at 40 years was significantly
      associated with a higher prevalence of sensitization at 40 years, but not with
      the incidence of sensitization. CONCLUSIONS: In older adults, aeroallergen
      sensitization as reflected by serum-specific IgE positivity to aeroallergens is a
      dynamic process. Both persistent and incident sensitization was associated with
      atopic disease. Further studies are needed to clarify the influence of alcohol on
      the allergen-specific IgE response.

PMID- 19752569
TI  - Novel and recurrent mutations in the C1NH gene of Arab patients affected with
      hereditary angioedema.
AB  - BACKGROUND: Autosomal dominant hereditary angioedema (HAE) results in episodes of
      subcutaneous edema in any body part and/or submucosal edema of the upper
      respiratory or gastrointestinal tracts. This disorder is caused by mutations in
      the C1NH gene, many of which have been described primarily in European patients.
      However, the genetic cause of HAE in Middle Eastern Arab patients has not yet
      been determined. METHODS: Four unrelated Arab families, in which 15 patients were
      diagnosed with HAE, were studied. DNA from 13 patients was analyzed for mutations
      in the C1NH gene by DNA sequencing. RESULTS: Three novel and 2 recurrent
      mutations were identified in the C1NH gene of HAE patients. In family 1, the
      patient was heterozygous for a novel c.856C>T and a recurrent c.1361T>A missense
      mutation encoding for p.Arg264Cys and p.Val432Glu, respectively. In patients from
      family 2, a novel c.509C>T missense mutation encoding for a p.Ser148Phe was
      identified. In patients from family 3, a novel c.1142delC nonsense mutation
      encoding for a p.Ala359AlafsX15 was discovered. In family 4, a recurrent
      c.1397G>A missense mutation encoding for a p.Arg444His was present. CONCLUSION:
      This is the first ever report of C1NH gene mutations in Middle Eastern Arab
      patients. Our study suggests that, despite the numerous existing mutations in the
      C1NH gene, there are novel and recurrent mutations in HAE patients of non
      European origin. We conclude that the spectrum of C1NH gene mutations in HAE
      patients is wider due to the likely presence of novel and recurrent mutations in
      patients of other ethnicities.

PMID- 19752570
TI  - Smad3 regulates dermal cytokine and chemokine expression and specific antibody
      production in murine responses to a respiratory chemical sensitizer.
AB  - BACKGROUND: The cytokine transforming growth factor-beta(TGF-beta) has important
      regulatory roles in the immune system. To investigate the role of intact TGF-beta
      signaling during the contact hypersensitivity (CHS) response to a respiratory
      allergen, we exposed Smad3-/- mice to topical trimellitic anhydride (TMA).
      METHODS: CHS was induced by topical application of TMA. The swelling of the TMA
      exposed ears was analyzed, and lymph node, ear tissue and skin biopsies were
      collected for RNA isolation, histology and histochemical analyses. Lymph node
      cell proliferation was measured and blood samples were collected for analysis of
      TMA-specific immunoglobulin. RESULTS: Topical TMA exposure resulted in increased
      mRNA expression of proinflammatory and suppressive cytokines (IL-1beta, TNF
      alpha, IL-6, IFN-gamma, IL-4, IL-10, IL-17, IL-23, TGF-beta), chemokines (CXCL9,
      CXCL10, CCL24) and chemokine receptors (CCR7, CCR8, CXCR2), increased numbers of
      CD3+ T cells in ear tissue, and lymphadenopathy in the Smad3-/- mice. The IL-10
      result was confirmed at the protein level by immunohistochemistry. However, the
      ear-swelling response and infiltration of eosinophils, F4/80+ cells, CD11c+ cells
      and mast cells were similar in the Smad3-/- mice compared to their wild-type (WT)
      siblings. While TMA-specific IgE was induced equally in the WT and Smad3-/- mice,
      the concentration of TMA-specific IgG2a was significantly lower in the Smad3-/-
      mice. CONCLUSIONS: The Smad3 molecule contributes significantly to the regulation
      of the cytokine and chemokine network during the CHS response to TMA. The lack of
      Smad3 resulted in a potent Th2 shift, confirmed by strongly impaired IgG2a
      levels.

PMID- 19752571
TI  - Autoimmune pancreatitis associated with myelodysplastic syndrome.
AB  - A 65-year-old man with myelodysplastic syndrome (MDS) was admitted for
      progressive jaundice. Diffuse pancreatic swelling and stricture of the main
      pancreatic duct were observed with elevated serum levels of direct bilirubin,
      aspartate transaminase, alanine transaminase, alkaline phosphatase, gammaGTP and
      amylase, and impaired glucose tolerance. Serum IgG and IgG4 levels were highly
      elevated, and both the direct antiglobulin test and platelet-associated IgG were
      positive. He was diagnosed with autoimmune pancreatitis associated with MDS, and
      biliary drainage followed by immunosuppressive therapy ameliorated the jaundice
      and laboratory findings. In addition to diffuse pancreatic FDG accumulation, fine
      incorporations of FDG to the lachrymal and submandibular glands were
      demonstrated, suggesting the recently proposed IgG4+ multiorgan
      lymphoproliferative syndrome (MOLPS). The etiology of IgG4+ MOLPS is still
      unknown; however, autoantibodies to blood cells in this case suggested that the
      autoimmune mechanism, which is caused by abnormal immune functions in MDS
      patients, might be involved in the pathogenesis of IgG4+ MOLPS.

PMID- 19752572
TI  - Occupational inhalant allergy to pork followed by food allergy to pork and
      chicken: sensitization to hemoglobin and serum albumin.
AB  - BACKGROUND: Animal-derived proteins are implicated in primary food allergies, but
      also in inhalant allergies with secondary food allergy symptoms. The objective of
      this study was to define the allergen(s) implicated in a case of food allergy to
      chicken meat, which developed in a person previously sensitized to pork after
      occupational exposure. METHODS: A 42-year-old female with a history of
      occupational inhalant allergy to pork reported rhinitis, asthma, dysphonia and
      conjunctivitis 30 min after ingestion of chicken. Skin tests were positive to
      chicken meat. Protein extracts were prepared from chicken meat. Allergens were
      characterized by IgE immunoblotting, N-terminal sequencing and ELISA. RESULTS:
      The patient showed specific IgE binding to chicken meat proteins at 12, 14, 26,
      55 and 65 kDa. N-terminal amino acid sequencing identified the 12- and 14-kDa
      proteins as the alpha- and beta-chain of hemoglobin. ELISA and immunoblot showed
      specific IgE binding to hemoglobin purified from chicken blood. IgE antibodies to
      chicken serum albumin were detected by ELISA. Inhibition studies with chicken and
      porcine hemoglobin as well as with serum albumins demonstrated cross-reactive IgE
      antibodies. CONCLUSIONS: We report a case of confirmed occupational inhalant
      allergy due to pork followed by food allergy to pork and 3 years later by food
      allergy to chicken. Porcine and chicken hemoglobin were found to be cross
      reactive allergens. Cross-reactivity between porcine and chicken serum albumin
      was possibly linked to a prior sensitization to cat serum albumin.

PMID- 19752573
TI  - Beneficial effects of combination therapy with olmesartan and azelnidipine in
      murine polycystic kidneys.
AB  - BACKGROUND: Some reports have discussed the synergic effects of angiotensin II
      receptor blockers and calcium channel blockers on vascular injury or
      microalbuminuria. The present study examined the effects of combination treatment
      with olmesartan and azelnidipine on polycystic kidney disease in a mouse model
      (DBA/2-FG pcy mouse) and its mechanisms. METHODS: The mice were divided into the
      following groups: combination treatment (n = 21), olmesartan treatment alone (n =
      23), azelnidipine treatment alone (n = 29) or untreated (n = 26). Mean blood
      pressure and kidney weight were measured at 4 and 8 weeks after the treatment.
      Renal expression of angiotensin II, gp91, nitrotyrosine and endothelial NO
      synthase (eNOS) were examined by immunostaining. In addition, extracellular
      signal-regulated kinase activation was evaluated by Western blotting. RESULTS:
      Olmesartan decreased the numbers of angiotensin II and gp91-positive cells,
      mainly macrophages, and cyst size at 4 weeks. However, only combination treatment
      suppressed cell infiltration, extracellular signal-regulated kinase activation
      and interstitial fibrosis with a significant change in the kidney weight/body
      weight ratio. The azelnidipine and combination treatment increased the numbers of
      interstitial eNOS-positive cells. CONCLUSION: The combination treatment protects
      against cyst enlargement in polycystic kidney disease by suppressing interstitial
      inflammation, fibrosis and oxidative stress by upregulating eNOS expression
      during disease course.

PMID- 19752574
TI  - Arterial stiffness in hemodialysis: which parameter to measure to predict
      cardiovascular mortality?
AB  - In previous studies, different parameters of arterial stiffness were related to
      cardiovascular mortality in hemodialysis patients, but their relative prognostic
      value has not previously been evaluated in 1 cohort. Carotid-femoral pulse wave
      velocity (PWV), the carotid augmentation index, carotid pulse pressure (CPP) and
      carotid-brachial pulse pressure amplification (AMP) were measured in 98 patients
      before and after hemodialysis. Patients were followed for a median of 29 months
      (1-34) and the association of these parameters with cardiovascular mortality were
      assessed using log-rank tests and Cox proportional hazards regressions. During
      follow-up, 25 patients died of cardiovascular causes. Increasing pre- and
      postdialysis PWV tertiles and decreasing predialysis AMP tertiles were
      significantly related to cardiovascular mortality (p = 0.012 and 0.011 for PWV,
      respectively; < 0.001 for AMP). Neither the carotid augmentation index nor
      carotid pulse pressure were related to cardiovascular mortality. The adjusted
      hazard ratios for 1 m/s higher pre- and postdialysis PWV were 1.24 (1.07-1.44)
      and 1.17 (1.06-1.28), respectively. The hazard ratio for 10% lower predialysis
      AMP was 1.41 (1.03-1.92). When included in the same model, both predialysis PWV
      and AMP remained significantly associated with cardiovascular mortality. Among
      different stiffness parameters, PWV is consistently related to cardiovascular
      mortality, irrespective of the timing of measurement. Predialysis AMP seems to
      provide additional prognostic information.

PMID- 19752575
TI  - Blood pressure in children with minimal change nephrotic syndrome during oedema
      and after steroid therapy: the influence of familial essential hypertension.
AB  - AIMS: To verify the variations of blood pressure in children with minimal change
      nephrotic syndrome and to correlate the blood pressure with familial history of
      essential hypertension. METHODS: We measured blood pressure in 49 prepubertal
      nephrotic children, 17 females and 32 males, in the first week of oedema, and
      after 4 weeks of ISKDC (International Study of Kidney Disease in Children)
      standard steroid therapy. The children were divided into two groups: one with and
      the other without familial history of essential hypertension. RESULTS: Among all
      the patients, 65% showed systolic and/or diastolic blood pressure higher than the
      90th percentile at the first assessment. Among the children with a familial
      history of essential hypertension, in the oedematous phase of the nephrotic
      syndrome, 88% showed blood pressure higher than the 90th percentile and no
      children showed blood pressure lower than the 75th percentile. After therapy, the
      percentage of children with blood pressure higher than the 90th percentile was
      52%. In the group with a negative familial history, at the onset 53% showed blood
      pressure over the 90th percentile. After 4 weeks of therapy, the percentage of
      children with blood pressure higher than the 90th percentile was 34%.
      CONCLUSIONS: Our study reveals the influence of familial essential hypertension
      in the oedematous phase of the nephrotic syndrome in children.

PMID- 19752576
TI  - The randomized controlled trial.
AB  - Until recently, high-quality randomized controlled trials (RCTs) have rarely been
      performed in nephrology, because of several difficulties in conducting an RCT.
      The purpose of this article is to describe several issues related to the design
      and to the quality of RCTs in their conduct, analysis, interpretation, and
      reporting of the results. The advantage of an RCT is that, as a result of
      randomization, selection by prognosis by the clinician is prevented. However, not
      all RCTs provide a definitive answer on the research question that the
      investigators try to answer because of potential problems in their design,
      conduct and analysis. For example, the results of an RCT could be biased if the
      physicians and patients in the experimental and control groups were not
      sufficiently 'blinded'. Nevertheless, if conducted properly, RCTs remain the gold
      standard for studying the effects of therapy and other interventions.

PMID- 19752577
TI  - Effect of intermittent hypercapnia on respiratory control in rat pups.
AB  - Preterm infants are subject to fluctuations in blood gas status associated with
      immature respiratory control. Intermittent hypoxia during early postnatal life
      has been shown to increase chemoreceptor sensitivity and destabilize the
      breathing pattern; however, intermittent hypercapnia remains poorly studied.
      Therefore, to test the hypothesis that intermittent hypercapnia results in
      altered respiratory control, we examined the effects of daily exposure to
      intermittent hypercapnia on the ventilatory response to subsequent hypercapnic
      and hypoxic exposure in neonatal rat pups. Exposure cycles consisted of 5 min of
      intermittent hypercapnia (5% CO(2), 21% O(2), balance N(2)) followed by 10 min of
      normoxia. Rat pups were exposed to 18 exposure cycles each day for 1 week, from
      postnatal day 7 to 14. We analyzed diaphragm electromyograms (EMGs) from pups
      exposed to subsequent acute hypercapnic (5% CO(2)) and hypoxic (12% O(2))
      challenges. In response to a subsequent hypercapnia challenge, there was no
      significant difference in the ventilatory response between control and
      intermittent hypercapnia-exposed groups. In contrast, intermittent hypercapnia
      exposed rat pups showed an enhanced ventilatory response to hypoxic challenge
      with an increase in minute EMG to 118 +/- 14% of baseline versus 107 +/- 13% for
      control pups (p < 0.05). We speculate that prior hypercapnic exposure may
      increase peripheral chemoreceptor response to subsequent hypoxic exposures and
      result in perturbed neonatal respiratory control.

PMID- 19752578
TI  - Cardiac output measurement in ventilated lambs with a significant left-to-right
      shunt using the modified carbon dioxide fick method.
AB  - BACKGROUND: It remains a great challenge to measure systemic blood flow in
      critically ill newborns. In a former study we validated the modified carbon
      dioxide Fick (mCO(2)F) method for measurement of cardiac output in a newborn lamb
      model. In this new study we studied the influence of a left-to-right shunt on the
      accuracy of the mCO(2)F method. OBJECTIVE: To analyze the influence of a left-to
      right shunt on the agreement between cardiac output measurement with the mCO(2)F
      method and ultrasonic transit time pulmonary blood flow in a lamb model. METHODS:
      The study was approved by the Ethical Committee on Animal Research of the Radboud
      University Nijmegen and performed in 8 random-bred lambs. A Gore-Tex shunt was
      placed between the left pulmonary artery and the descending aorta. This
      aortopulmonary shunt was intermittently opened and closed, while cardiac output
      was manipulated by creating hemorrhagic hypotension. Cardiac output measurement
      with the mCO(2)F method (Q(mCO2F)) was compared with pulmonary blood flow
      obtained by a transit time ultrasonic flow probe positioned around the common
      pulmonary artery (Q(APC)). RESULTS: Bias, defined as Q(mCO2F) - Q(APC), was
      calculated for each measurement. With an open shunt there was a significant left
      to-right shunt (mean Qp/Qs ratio 2.26; range 1.56-3.69). Mean bias (SD) was -12.3
      (50.4) ml x kg(-1) x min(-1) and -12.3 (42.7) ml x kg(-1) x min(-1) for
      measurements with a closed and open shunt, respectively (no statistical
      significant difference). CONCLUSIONS: Cardiac output measurement with the mCO(2)F
      method is reliable and easily applicable in ventilated newborn lambs, also in the
      presence of a significant left-to-right shunt.

PMID- 19752579
TI  - Correlation of brain white matter diffusion anisotropy and mean diffusivity with
      reaction time in an oddball task.
AB  - BACKGROUND: Reaction time (RT) is a frequently used measure of information
      processing speed, but the underlying physiological and anatomical conditions are
      not yet fully understood. A correlation between measures of white matter (WM)
      ultrastructural properties and RT is expected--particularly for those WM tracts
      that are involved in the attentional system of the brain. METHODS: Diffusion
      tensor imaging data were acquired in 43 unrelated healthy subjects (age: 22.7 +/-
      1.8 years), and RT was measured during an attention-requiring visual oddball task
      in the same scanning session. Voxel-by-voxel and region of interest analyses were
      performed for the large association tracts. A linear regression model was used to
      correlate fractional anisotropy (FA) and mean diffusivity (MD) values with mean
      RT. RESULTS: Our analyses revealed significant positive correlations between RT
      and MD in several WM association tracts, predominantly in the right hemisphere.
      To a lesser extent, significant negative correlations were found between RT and
      FA in right temporal WM. CONCLUSION: These findings suggest that subcortical
      ultrastructural properties of the dorsal and ventral visual stream are relevant
      with regard to information processing speed. Furthermore, MD appears to be more
      sensitive than FA in detecting functionally relevant ultrastructural variations
      in WM tracts.

PMID- 19752580
TI  - Apolipoprotein E polymorphism and clinical disease phenotypes in Arab patients
      with schizophrenia.
AB  - BACKGROUND: Apolipoprotein E (APOE) is polymorphic, and may be involved in the
      pathogenesis and clinical expression of schizophrenia. This study aimed to
      investigate the frequency of specific APOE genotypes and alleles in a
      schizophrenic Arab population and evaluate the association of specific APOE types
      with clinical phenotypes of the disease. SUBJECTS AND METHODS: Two age-matched
      groups of subjects were studied: (1) healthy controls, n = 165; (2) patients with
      schizophrenia (SZ), n = 207. Each subject was evaluated for age and mode of onset
      of disease, family history of psychosis, disease severity and outcome over the
      years of illness. APOE genotyping was performed by a validated PCR-RFLP
      technique. RESULTS AND DISCUSSION: Genotype E3E2 and allele E2 were less frequent
      in the patients with schizophrenia (p = 0.04), and both APOE types tended to be
      more common in male than female schizophrenic patients (p = 0.08). Schizophrenic
      patients with a positive family history of psychosis had lower frequencies of
      genotype E3E2 and allele E2 (both p = 0.04). Genotype E3E4 and allele E4 were
      least common in patients with an age at onset of disease >31 years (OR: 5.5, 95%
      CI: 1.1-27.4), particularly in males. CONCLUSION: APOE genetic polymorphism
      potentially influences susceptibility to schizophrenia and may be associated with
      aspects of its phenotypic expression, particularly gender, age of onset and
      family history of psychotic illness. This relationship of APOE with schizophrenia
      is likely to be race- and gender-specific.

PMID- 19752581
TI  - Arachidonic acid supplementation decreases P300 latency and increases P300
      amplitude of event-related potentials in healthy elderly men.
AB  - In the present study, we examined the effects of arachidonic acid (ARA) on age
      related event-related potential (ERP) changes in 25 healthy elderly men. This
      study was performed using a double-blind crossover design. The subjects were
      administered 600 mg/day of ARA-enriched triglyceride (SUNTGA40S; containing 240
      mg ARA) in capsules or the same amount of olive oil in capsules as an inactive
      placebo for 1 month. ERPs were measured before capsule administration and after 1
      month of administration, and P300 latency and amplitude were also measured. In
      subjects administered 240 mg/day ARA, P300 latency was significantly shorter, and
      P300 amplitude was significantly higher than in those administered olive oil
      capsules, and they exhibited a significant increase in ARA content in serum
      phospholipids. These findings suggest that supplementation of ARA can improve
      cognitive function in healthy elderly men.

PMID- 19752582
TI  - Quantitative motor activity differentiates schizophrenia subtypes.
AB  - BACKGROUND: Motor symptoms are frequent in schizophrenia and relevant to the
      diagnosis of subtypes. However, the assessment has been limited to observations
      recorded in scales and experimental designs. The aim of this study was to use
      wrist actigraphy to obtain motor activity data in 3 schizophrenia subtypes.
      METHODS: In total, 60 patients with schizophrenia (35 paranoid, 12 catatonic, 13
      disorganized) were investigated using continuous wrist actigraphy over 24 h in an
      inpatient setting on average 38 days after admission. Data of the wakeful hours
      of the day were analyzed. RESULTS: The activity level was predicted by
      schizophrenia subtype and by the type of antipsychotic medication. The movement
      index and mean duration of uninterrupted immobility were found to be predicted
      only by the schizophrenia subtype. Age, gender, duration of illness and
      chlorpromazine equivalents did not contribute to the variance of the activity
      data. A MANOVA demonstrated the significant differences in the 3 parameters
      between schizophrenia subtypes (p = 0.001). Patients with catatonic schizophrenia
      had lower activity levels, a lower movement index and a longer duration of
      immobility than those with paranoid schizophrenia. CONCLUSIONS: Schizophrenia
      subtypes can be differentiated using objective measures of quantitative motor
      activity. The increased duration of immobility appears to be the special feature
      of catatonic schizophrenia.

PMID- 19752583
TI  - Spontaneous reattachment of the margins of a macular retinal pigment epithelium
      tear: optical coherence tomography documentation of a case.
AB  - PURPOSE: To document by optical coherence tomography (OCT) the reattachment of
      the margins of a retinal pigment epithelium (RPE) tear. METHODS: Single case
      report, documented by OCT scans, autofluorescence and fluorescein angiography.
      RESULTS: A 67-year-old male presented with a spontaneous RPE tear due to age
      related macular degeneration in his right eye. Three months later we observed
      that the focal RPE tear had healed and there was a new intraretinal fluid, well
      documented by OCT imaging. CONCLUSIONS: OCT scans show the reattachment of the
      margins of an RPE tear healed by tissue remodelling, and illustrate how the
      disease can recur.

PMID- 19752584
TI  - Prevention of free fatty acid-induced hepatic lipotoxicity in HepG2 cells by
      magnesium isoglycyrrhizinate in vitro.
AB  - BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver
      disease that threatens public health, and current therapies remain limited. This
      study investigated the protective effect of magnesium isoglycyrrhizinate (MGL), a
      novel compound, against free fatty acid (FFA)-induced lipotoxicity in a cellular
      model of steatosis. METHODS: HepG2 cells were incubated with 1 mmol/l FFAs
      together with MGL for 24 h. Cell viability was assessed using the MTT assay. Cell
      apoptosis was determined by Hoechst staining. Intracellular lipids were measured
      by flow cytometry using Nile red. Mitochondrial function was analyzed by
      detecting transmembrane potential, cytochrome c release and reactive oxygen
      species' production. RESULTS: MGL protected cell viability and dramatically
      decreased FFA-induced cell apoptosis and lipid accumulation. MGL was found to
      inhibit mitochondrial transmembrane polarization, and decrease mitochondrial
      cytochrome c release and the generation of reactive oxygen species. CONCLUSION:
      This study demonstrated that MGL attenuates FFA-induced lipotoxicity by reducing
      mitochondrial damage, which indicates a promising therapeutic intervention for
      NAFLD.

PMID- 19752585
TI  - Pharmacokinetics of propofol and extrahepatic UGT1A6 gene expression in anhepatic
      rats.
AB  - OBJECTIVE: The metabolic enzyme of UDP-glucuronosyltransferase 1A6 (UGT1A6) has
      been considered to metabolize propofol intra- or extrahepatically. The aim of the
      present study was to investigate the pharmacokinetics of propofol and UGT1A6 mRNA
      expression in extrahepatic organs before and during the anhepatic status in rats.
      METHODS: Male Sprague-Dawley rats were injected with propofol (10 mg/kg)
      intravenously and a blood sample was taken at 2-60 min after injection. The
      hepatic hilum was occluded under laparotomy and then the propofol injection and
      blood sampling were repeated as above 24 h later. The plasma concentrations of
      propofol were analyzed and UGT1A6 mRNA expression in the kidney, small intestine,
      lung and brain from other cohort rats at 30 and 60 min of anhepatic status were
      semiqualified by RT-PCR. RESULTS: T(1/2)(alpha), T(1/2)(beta) and V(d) of
      propofol were not changed significantly before and during the anhepatic status.
      The area under curve, derived from a time-dependent concentration response curve,
      was significantly increased whereas plasma clearance rate was decreased
      significantly in the anhepatic period when compared to that in the control
      period, respectively. UGT1A6 mRNA expression in extrahepatic organs was
      significantly increased at 30 or 60 min of the anhepatic status when compared to
      those in the control status. CONCLUSION: The pharmacokinetics of propofol during
      the prehepatic and anhepatic status are largely similar, which is associated with
      the upregulation of extrahepatic UGT1A6 gene. The marginal accumulation of
      propofol during anhepatic period is likely to be due to both the limited function
      of this metabolic pathway and physiological disturbance induced by hepatic hilum
      occlusion.

PMID- 19752586
TI  - Characterization of two models of drug-induced constipation in mice and
      evaluation of mustard oil in these models.
AB  - Although it is known that both clonidine and loperamide cause delayed colonic
      transit in mice, these models of drug-induced experimental constipation have not
      yet been fully characterized. Therefore, the aims of this study were to validate
      the clonidine- and loperamide-induced delays of colonic transit in mice as models
      of atonic and spastic constipation, respectively, and to evaluate the effect of
      mustard oil, a TRPA1 agonist, in both models. Colonic transit was evaluated in
      mice by determining the time needed to evacuate a bead inserted into the distal
      colon. Both loperamide and clonidine dose-dependently prolonged the evacuation
      time. Clonidine (10 microg/kg) and loperamide (0.3 mg/kg) tripled the evacuation
      time compared to controls. These delays were antagonized by the administration of
      yohimbine and naloxone, respectively. Tegaserod, a gastrointestinal motor
      stimulating drug, reversed the delay in both models, but the effects were
      diminished at high doses. Atropine, an antispastic drug, improved the loperamide
      induced delay, but did not affect the clonidine-induced delay. Mustard oil
      accelerated the colonic transit dose-dependently in both models of drug-induced
      constipations. These results indicate that clonidine- and loperamide-induced
      delays in colonic transit are models of atonic and spastic constipation,
      respectively, and that mustard oil may be effective on both types of
      constipation.

PMID- 19752587
TI  - Epistemology of mental symptoms.
AB  - BACKGROUND AND METHODS: Psychiatric diagnosis is dependent on the identification
      of mental symptoms. On the assumption that they are 'natural kinds', the latter
      are routinely entered as correlational variables in empirical research. Published
      work on the philosophy of psychiatry has tended to concentrate on the concept of
      mental disorder or on individual symptoms but has given less attention to mental
      symptoms as a class. This paper deals specifically with the epistemology of
      mental symptoms, that is, with focusing on the nature of mental symptoms as a
      class of 'objects' and how the clinician gets to know them. In order to do this,
      mental symptoms can be explored from various perspectives, namely: (i) as types
      of objects, (ii) as structures, (iii) as definitions, (iv) as pockets of
      meanings, (v) as comprising constituents, (vi) as attractors in specific
      dialogical contexts, etc. In this paper, on account of space constraints, we deal
      only with the former 4 perspectives. RESULTS AND CONCLUSION: Our analysis shows
      mental symptoms to be unstable constructs with implications for both
      correlational research and further theoretical exploration.

PMID- 19752588
TI  - Reasons for cannabis use and effects of cannabis use as reported by patients with
      psychotic disorders.
AB  - BACKGROUND: Cannabis is one of the most commonly used substances in patients with
      a psychotic disorder and is associated with a higher risk of psychotic relapses.
      Identifying reasons for cannabis use and subjective effects in patients with
      psychotic disorders can provide insight into the functions of cannabis use, and
      this may lead to targeted interventions. METHODS: A literature search of the
      PubMed and PsycINFO databases for articles published from 1985 till 2008 was
      carried out to review studies that examined self-reported reasons for cannabis
      use and self-reported effects of cannabis use in patients with psychotic
      disorders. RESULTS: Only a few studies were found that specifically assessed
      reasons for and effects of cannabis use. Despite the heterogeneity in the study
      samples and methodology, patients commonly reported that their reasons for
      cannabis use were enhancement of positive affect, relief of dysphoria and social
      enhancement. Fewer patients reported reasons related to relief of psychotic
      symptoms or relief of side effects of medication. Frequently reported positive
      effects of cannabis were positive changes in affect and relaxation. A large
      proportion of patients reported that cannabis negatively affected positive
      symptoms. CONCLUSIONS: Patients suffering from psychotic disorder report using
      cannabis mainly for affect regulation and socialization, despite the awareness
      that cannabis has a negative effect on positive symptoms. In spite of the
      heterogeneity of the studies, the results turned out to be broadly comparable and
      support the external validity of this review to a broad range of cannabis-using
      patients with psychotic disorder.

PMID- 19752589
TI  - Anomalous self-experience in adolescents at risk of psychosis. Clinical and
      conceptual elucidation.
AB  - BACKGROUND: In research and clinical settings, there is a growing interest in the
      prodromal state of psychosis. The condition is usually operationalized by the
      presence of weak positive symptoms. Some studies also point to disorders of self
      awareness as a core characteristic of the schizophrenia spectrum detectable
      before the onset of psychosis. Combining the 2 approaches is a pragmatic solution
      to the investigation of the role of anomalous self-experience in developing
      psychosis. METHODS: This clinical report describes disorders of self-experience
      in a small sample of 11 subjects fulfilling the Criteria of Prodromal Syndromes.
      All subjects were interviewed using the symptom checklist Examination of
      Anomalous Self-Experience. Through in-depth analysis of cases, interview excerpts
      have been selected for the purpose of illustrating the phenomena of anomalous
      self-experience. RESULTS: Disorders of self-experience were found in all subjects
      who fulfilled the prodromal criteria. There was, however, a difference in the
      kind and numbers of single features. Examples of disorders of self-experience
      which differ from the attenuated positive symptoms are illustrated by selected
      interview excerpts. CONCLUSIONS: Anomalous self-experience should be further
      investigated in subjects at risk of psychosis and in a broader clinical
      population. The concept of anomalous self-experience should be further elaborated
      theoretically as well as empirically.

PMID- 19752590
TI  - Development and psychometric characteristics of the DSS-4 as a short instrument
      to assess dissociative experience during neuropsychological experiments.
AB  - BACKGROUND/AIMS: Until now, no brief self-report instrument for the assessment of
      dissociative states comprising somatoform and psychological items has been
      available. Thus, we developed a brief instrument for repeated assessment of
      dissociation during single neuropsychological experiments and neuroimaging.
      METHODS: Based on specific criteria, 4 items were derived from an already
      existing scale for the assessment of dissociative symptoms (Dissociation-Tension
      Scale acute, DSS-acute). These 4 items were presented to a total of 142 female
      patients with different disorders and healthy controls every hour over a 48-hour
      period. Data acquisition was done with a handheld PC. RESULTS: Inner consistency,
      reliability and differential validity can be considered to be good or excellent.
      The DSS-4 was sensitive to changing symptomatology within the 48-hour period and
      additionally within a 3-hour period. CONCLUSION: Taken together, our newly
      developed instrument provides a reliable and easy-to-use tool for the assessment
      of psychological and somatic aspects of dissociative states, for example for the
      use at multiple times during single neuropsychological experiments or
      neuroimaging. There are some indicators that the DSS-4 is a valid instrument.

PMID- 19752591
TI  - Negative performance beliefs and negative symptoms in individuals at ultra-high
      risk of psychosis: a preliminary study.
AB  - BACKGROUND: Negative beliefs regarding task performance have been shown to
      correlate with negative symptom severity in patients with chronic schizophrenia.
      We conducted a pilot study to determine whether the association also exists in
      individuals at ultra-high risk of psychosis. SAMPLING AND METHODS: The sample
      consisted of 38 individuals at ultra-high risk of psychosis and 51 controls. All
      participants completed the Abbreviated Dysfunctional Attitudes Scale; the ultra
      high-risk participants were assessed with the Positive and Negative Syndrome
      Scale. RESULTS: High-risk participants endorsed negative performance beliefs to a
      greater extent than controls and these beliefs were associated with greater
      negative symptom severity, independent of depression and positive symptoms.
      CONCLUSIONS: The findings are consistent with previous results in chronic
      patients, and suggest that negative performance beliefs may be a promising
      psychological factor worthy of further attention in individuals at high risk of
      psychosis. Longitudinal research with more comprehensive assessment is needed to
      elucidate the potential role of negative performance beliefs in this population.

PMID- 19752592
TI  - Subthalamic nucleus location: relationships between stereotactic AC-PC-based
      diagrams and MRI anatomy-based contours.
AB  - Subthalamic nucleus (STN) targeting is classically performed based on AC-PC
      probabilistic position. Nevertheless, MRI allows direct visualization and
      targeting. We aimed to compare the position localized on MR images with standard
      stereotactic diagrams. The STN was manually contoured on MR images (22
      Parkinson's disease patients); boundaries were simplified in a schematic
      polygonal form. Front and lateral stereotactic diagrams were constructed
      according to Talairach and Benabid. We compared x, y and z coordinates of the
      geometrical center of MRI-based polygons and stereotactic diagrams (Wilcoxon
      matched-pairs tests). There was significant discordance between MRI-based
      polygons and AC-PC-based images. MRI shows the STN as more posterior, medial and
      slightly inferior.

PMID- 19752593
TI  - Deep brain stimulation electrode used for radiofrequency lesion of the globus
      pallidus internus in dystonia.
AB  - BACKGROUND: There have recently been increasing case reports in the literature of
      deep brain stimulation (DBS) electrodes used for lesioning with satisfactory
      clinical success in the treatment of Parkinson disease and tremor. METHODS: After
      preliminary experiments of radiofrequency (RF) lesioning with a quadripolar DBS
      lead, a paediatric case of generalized primary dystonia was treated by RF
      lesioning of the globus pallidus internus (Gpi) with an electrode previously used
      for chronic stimulation. In order to study electrode damage related to the RF
      procedure, an electron microscopy study (SEM) at different magnifications (x40
      and x300) was performed. RESULTS: Nine months after the unilateral pallidotomy,
      the patient had a good and stable control of dystonia. The MR study showed a T(1)
      weighted hyperintensity signal corresponding to the electrode contacts used for
      lesions. The SEM scans of the DBS electrode used for RF lesioning did not show
      alterations of the ultrastructure. CONCLUSIONS: The RF lesioning technique by a
      DBS electrode allows small and staged lesions and could also be performed in a
      bilateral target. The versatility, efficacy, safety and low cost of the device
      make this approach suitable in selected cases.

PMID- 19752594
TI  - Wire tethering or 'bowstringing' as a long-term hardware-related complication of
      deep brain stimulation.
AB  - BACKGROUND: Widely reported long-term complications following implantation of
      deep brain stimulation (DBS) hardware include breakage of electrode leads,
      internal pulse generator (IPG) failure, skin erosions and infection. Here we
      report on a rarely described problem that arises from formation of scar tissue
      adhesions around the DBS extension wire(s). Over time, this scar tissue can
      become tight and pronounced, protruding noticeably beneath the skin
      ('bowstringing' in reference to its tight bow-like appearance) and leading to
      significant limitation of movement and discomfort. We term this 'wire tethering'.
      RESULTS: We describe 6 patients with moderate to severe wire tethering. Review of
      our experience suggests an association of wire tethering with the passage of two
      extension wires on the same side as is done when using a dual-channel IPG. Five
      of the patients required surgical revision of the extension wires due to the
      magnitude of the discomfort, limitation of movement and appearance. Removing the
      wires was insufficient in the most severe case, necessitating transection of the
      scar in several places, which was done with the extension wires in situ in 2
      patients. Two patients were treated with removal of the wires alone, and 1
      patient did not opt for surgery and the tethering has persisted. CONCLUSION: Wire
      tethering, or 'bowstringing', is an underrecognized complication of DBS hardware
      implantation often necessitating surgical revision. The possible etiology of wire
      tethering is discussed as well as suggestions for its avoidance.

PMID- 19752595
TI  - Stereotactic radiosurgery of residual or recurrent craniopharyngioma: new
      treatment concept using Leksell gamma knife model C with automatic positioning
      system.
AB  - BACKGROUND/AIMS: The present study analyzed the initial experience with the
      application of the original concept of 'robotic microradiosurgery' using Leksell
      Gamma Knife Model C with automatic positioning system for management of
      craniopharyngiomas. METHODS: Eighteen patients with residual or recurrent
      craniopharyngiomas underwent radiosurgery with the use of multiple isocenters,
      mainly of smaller size, which were positioned compactly within the border of the
      lesion with resultant improved dose homogeneity, increased average dose within
      the target, and sharp dose fall outside the treated volume. Treatment planning
      was mainly guided by constructive interference in steady state images with and
      without gadolinium enhancement. Mean tumor volume was 1.8 cm(3). In 12 cases the
      anterior visual pathways were either compressed or attached to the lesion. The
      average number of isocenters was 8.7 per cubic centimeter of target volume. Mean
      marginal irradiation dose was 11.6 Gy. Mean maximal dose to the anterior visual
      pathways was 8.4 Gy. Mean follow-up was 26.8 months, and median follow-up was 24
      months. RESULTS: Tumor growth was controlled in 17 cases (94%), and its volume
      reduction was attained in 13 cases (72%). In 3 patients significant shrinkage of
      the neoplasm after radiosurgery was accompanied by improvement of the visual
      functions. Their impairment was not marked in any case, nor was there any new
      endocrinopathy. CONCLUSION: Application of robotic microradiosurgery to the
      management of residual and recurrent craniopharyngiomas showed promising results
      during short- to intermediate-term follow-up, providing early tumor shrinkage in
      the majority of cases as well as sparing of visual and pituitary functions.

PMID- 19752596
TI  - Mix gonadal dysgenesis associated with ring Y chromosome mosaics in a phenotypic
      male.
AB  - Ring chromosomes are present in 1 in 25,000 human fetuses; 99% arise de novo
      while less than 1% of rings are inherited. This chromosomal rearrangement may
      arise through a cytogenetic mechanism involving breaks in chromosome arms and
      fusion of the proximal broken ends, leading to a loss of distal material. Most
      patient Y ring chromosomes are present in a 45,X/46,X,r(Y) mosaic karyotype;
      molecular analyses of infertile men have shown that it is not rare to find r(Y)
      in these patients. However, the clinical spectrum in those cases with a 45,X cell
      line is broad and depends on the percentage of the monosomic cell line in
      different tissues. Y chromosome abnormalities and 45,X mosaic karyotypes are
      often associated with disorders of sex determination. Here, we report a male
      patient with hypospadias, cryptorchidism and a mosaic karyotype containing a low
      proportion of 45,X monosomic cells and multiple ring Y chromosomes in peripheral
      blood. Clinical, surgical, and molecular evidence was sufficient for a diagnosis
      of mixed gonadal dysgenesis. We suggest that a detailed cytogenetic and molecular
      analysis should be done in all males with bilateral descended testes and
      infertility.

PMID- 19752597
TI  - Hidden X chromosomal mosaicism in a 46,XX male.
AB  - We report on a 37-year-old XX male with complex hidden X chromosomal mosaicism.
      The patient had fully mature male genitalia with hypoplastic testes descended in
      the scrotum and no sign of undervirilization. Hormonal examination demonstrated
      hypergonadotropic hypogonadism, semen analysis showed severe
      oligoasthenoteratozoospermia. In situ hybridization revealed the presence of 3
      SRY-positive cell lines bearing 1, 2 or 3 X chromosomes. Skewed inactivation of
      the paternal SRY-bearing X chromosome was detected by molecular analysis of the
      androgen receptor gene.

PMID- 19752598
TI  - Body composition and metabolic profile in women with complete androgen
      insensitivity syndrome.
AB  - Clinical and experimental data suggest that androgen receptor (AR) signaling
      plays a role on body composition, glucose homeostasis and lipid metabolism. The
      effect of AR disruption on such parameters was not extensively investigated in
      human people. A group of young to middle-age adult women with complete androgen
      insensitivity syndrome (CAIS, n = 18, age 32.2 +/- 9.3 years; women with testes
      removed n = 14) was investigated for body mass index (BMI), body composition
      (dual energy X-ray absorptiometry), serum glucose levels, insulin sensitivity
      (HOMA-IR) and lipid profile. Mean BMI (24.2 +/- 7.4 kg/m(2)) was not
      significantly increased (T-score 1.0 +/- 2.5, p = NS vs Italian female reference
      values), but prevalence of obesity was higher in women with CAIS than that
      reported in age-related Italian females (16.7% vs 3.6%, respectively). The
      majority of obese individuals with CAIS was in the subgroup with intact testes
      (3/4). DXA assessment (n = 15) demonstrated values of total free fat mass similar
      to that of 46,XX female controls. Increased body fat was found in CAIS women in
      comparison with both female and male controls. Abnormal values of cholesterol
      (total and LDL) and HOMA-IR were present in a large subset of patients. Our data
      suggest that in women with CAIS disruption of AR signaling may increase body fat
      and affect some metabolic parameters. Assessment of body composition, metabolic
      profile and, likely, cardiovascular risk seems to be advisable with ageing in
      these individuals.

PMID- 19752599
TI  - Identification of suitable normalizing genes for quantitative real-time RT-PCR
      analysis of gene expression in fetal mouse gonads.
AB  - In biological research, quantitative real-time reverse transcription polymerase
      chain reaction (qRT-PCR) assays are commonly employed to study mRNA abundance in
      cells and tissues. This type of assay usually relies on assessing transcript
      abundance relative to constitutively expressed endogenous reference genes.
      Therefore, it is important that the reference genes themselves are stably
      expressed in the cells or tissues analyzed, independent of factors such as age,
      sex, disease or experimental manipulations. Since no gene is expressed at the
      same level in all cells at all times, suitable reference genes must be identified
      for the specific cellular system or tissue being investigated. Here, we sought to
      identify stably expressed endogenous reference genes during embryonic gonad
      development in the mouse. We measured the transcript abundance of 10 frequently
      employed normalizing genes, of which 4 were stably expressed in fetal gonads from
      11.5 to 14.5 dpc irrespective of sex. Based on our analysis, we suggest that
      Rn18s, Rps29, Tbp and Sdha are suitable reference genes for qRT-PCR expression
      studies during early gonad differentiation in the mouse.

PMID- 19752600
TI  - Copy number variation of testis-specific protein, Y-encoded (TSPY) in 14
      different breeds of cattle (Bos taurus).
AB  - Multi-copied gene families are prevalent in mammalian genomes, especially within
      the Y chromosome. Testis specific protein Y-encoded (TSPY) is present in variable
      copy number in many mammalian species. Previous studies have estimated that TSPY
      ranges from 50-200 copies in cattle. To examine TSPY localization on the Y
      chromosome we employed fluorescence in situ hybridization (FISH) and fiber-FISH.
      The results show a strong signal on the short arm of the Y chromosome (Yp). To
      investigate TSPY copy number we used relative real-time polymerase chain reaction
      (PCR) to analyze the DNA of 14 different cattle breeds. Variation both within and
      between breeds was observed. All breeds show significant variation in TSPY copy
      number among individual members. Brown Swiss (161 copies, CI = 133-195) had
      higher average levels of TSPY and Western Fjord Cattle (63 copies, CI = 45-86)
      had lower levels than some breeds. Overall, however, most breeds had a similar
      average TSPY copy number. The pooled average was 94 copies (CI = 88-100). The
      significance of the TSPY array remains uncertain, but as the function of TSPY is
      unraveled the purpose of the array may become clearer.

PMID- 19752601
TI  - Identification of novel genes associated with molecular sex differentiation in
      the embryonic gonads of rainbow trout (Oncorhynchus mykiss).
AB  - The molecular pathways in embryonic vertebrates leading to gonad formation in
      each sex are incompletely understood. The purpose of this study was to identify
      novel genes that could be associated with sex-specific gonadal differentiation in
      a fish, the rainbow trout (Oncorhynchus mykiss). This study was facilitated by a
      custom microarray based on 7,671 genes derived from embryonic rainbow trout gonad
      cDNA libraries and public databases. Gonad samples for total RNA isolation were
      obtained from pvasa-green fluorescent protein (pvasa-GFP) transgenic rainbow
      between 300 and 700 degree-days of development post-fertilization. The transgenic
      fish permitted the collection of gonads from embryonic rainbow trout during the
      period of molecular sex differentiation in advance of any morphologically
      distinguishable characteristics of sex. A bioinformatic method was used with the
      microarray data that looked for strong associations in gene expression patterns
      between known sex differentiation genes (the target genes) and novel genes (the
      target-associated genes) previously not allied with sex differentiation in
      fishes. The expression patterns of representative target genes from both sexes
      and their target-associated genes were independently confirmed by real-time
      reverse transcription polymerase chain reaction to support the validity of the
      bioinformatic method employed. Numerous novel genes were identified in the gonads
      of embryonic female and male rainbow trout that could be involved in sex-specific
      differentiation pathways in this fish.

PMID- 19752602
TI  - Germ cell degeneration in high-temperature treated pufferfish, Takifugu rubripes.
AB  - Exogenous factors such as temperature, social behavior, and salinity play a
      crucial role during the critical sensitive period of sex differentiation in many
      vertebrates. In fishes, amphibians, and reptiles temperature treatment is known
      to induce all-male (or female) individuals, and genes related to sex
      differentiation have been studied. The Japanese pufferfish, Takifugu rubripes,
      possesses the most compact genome among vertebrates and has immense potential for
      studies focusing on comparative genome analysis. In this study, we describe
      gonadal morphology and vasa (germ cell marker) and dmrt1 (Sertoli cell marker)
      expression on a molecular level in relation to the development of temperature
      treated pufferfish. To investigate the relationship between temperature and
      gonadal development, pufferfish were exposed to high-temperature conditions (32
      degrees C) during early gonadal development. Morphological observations showed
      that this high-temperature treatment did not influence sexual differentiation as
      determined by ovarian cavity characteristics; however, high-temperature treatment
      induces gonadal degeneration that is devoid of germ cells. RT-PCR results
      revealed no vasa expression within germ cell-degenerated gonads. In situ
      hybridization results showed that dmrt1 was expressed in somatic cells of germ
      cell-degenerated ovaries. These results suggest that high-temperature treatment
      during early gonadal development induces germ cell degeneration and
      masculinization of ovarian somatic cells in pufferfish.

PMID- 19752603
TI  - 15-lipoxygenase-1 in colorectal cancer: a review.
AB  - OBJECTIVE: Enzymes involved in the oxidative metabolism of n-6 polyunsaturated
      fatty acids, like lipoxygenase (LOX) and cyclooxygenase (COX), are significant in
      the pathogenesis of colorectal cancer. Of these enzymes, 15-LOX-1 is expressed in
      colon. Aim of this article is to describe the role and regulation of 15-LOX-1 in
      colorectal cancer and highlight its importance in cancer therapeutics. METHODS:
      For our electronic literature research in PubMed and MEDLINE, key words related
      to 15-LOX-1 and colorectal cancer were used to find articles for this review.
      RESULTS: From the evidences, we believe that 15-LOX-1 has anti-carcinogenic
      effects in colorectal cancer, dependent or independent of its metabolites, and is
      manifested through downstream pathways involving cGMP, PPAR, p53, p21 and NAG-1,
      increasing apoptosis and decreasing proliferation in cancer cells. Regulation of
      15-LOX-1 expression is achieved at transcription level by global histone
      acetylation and may also be dependent on GATA-6, IL-4 and IL-13. Positive
      relationship exists between 15-LOX-1 and survival in colorectal cancer.
      CONCLUSION: Evidences strongly support that therapeutic modulation of 15-LOX-1
      may be a key to the treatment of colorectal cancer. However, it is still
      undecided whether the up-regulation of 15-LOX-1 alone can be sufficient to treat
      colorectal cancer and further studies are awaited.

PMID- 19752604
TI  - Urethral instability: current pathophysiological concept.
AB  - The role of urethral pressure variations during filling cystometry is seldom
      assessed as a potential cause of voiding dysfunction and/or storage disorders. In
      this article, we review current research in the field of urethral pressure
      variations and discuss the way of determining urethral pressure variations, its
      value for the clinical practice and hypothesize the origin of urethral pressure
      variations. The observation and recognition of urethral pressure variations
      (urethral instability) could be valuable in the diagnosis and evaluation of
      therapy in functional lower urinary tract disorders.

PMID- 19752605
TI  - Decrease in prostate cancer incidence and mortality in Germany - effects of
      opportunistic PSA screening or more?
AB  - BACKGROUND: An increasing incidence and controversial interpretations about the
      valuation of improved survival rates are the main subjects of the discussion
      dealing with the epidemiology of the prostate carcinoma. In this study the most
      recent data of the Cancer Registry Schleswig-Holstein (the northernmost state of
      Germany) are introduced. MATERIALS AND METHODS: Data from the population-based
      cancer registry covering a population of 2.8 million inhabitants were evaluated
      descriptively for the years 1999-2005. RESULTS: The frequency of more prognostic
      favourable diagnosis rose in the analyzed period. In 2000-2001, 62.9% of the
      patients were diagnosed with stage I/II and in 2004-2005 the percentage rose to
      67.9%. From 1999 to 2003 the age-adjusted incidence increased by 30% and declined
      to the level of 1999 within 2 years. Mortality decreased continuously and from
      1999 to 2005 it dropped by 20%. CONCLUSION: We assume that a selected group of
      men in Schleswig-Holstein has been screened regularly by PSA testing. The rise of
      incidence could be interpreted as a typical effect of a screening prevalence
      round. Thereafter the incidence declined because of the initial screening effect.
      However, it is not yet evident whether the PSA tests will have further effects on
      mortality rates.

PMID- 19752606
TI  - Cystoprostatectomy as a treatment of prostate cancer involving the bladder neck.
AB  - OBJECTIVE: We evaluated the clinicopathological findings and short- and long-term
      outcomes of prostate cancer (PCa) patients with bladder neck invasion who
      underwent cystoprostatectomy. PATIENTS AND METHODS: Between 1989 and 2005, we
      performed 17 cystoprostatectomies for PCa patients having bladder neck invasion
      without distant visceral or distant lymph node metastasis. Of the 17 patients, 11
      were treated with neoadjuvant hormone therapy and all patients were treated with
      adjuvant hormone therapy immediately after surgery. RESULTS: All 7 patients in
      whom pelvic lymph node swelling was identified by preoperative imaging studies
      had pathological lymph node metastasis. Of the 10 patients judged as cN0
      preoperatively, 7 (70.0%) had lymph node metastasis. Although local recurrence
      was found in 2 (11.8%) patients, no additional urinary diversion or inconvenient
      urinary symptoms due to PCa progression were observed in any patients. The 5-year
      prostate-specific antigen recurrence-free survival rate was 62.2%. Cause-specific
      survival at 5 years after surgery was 87.1%. The 5-year cause-specific survival
      rate of node-positive patients was 92.3%. CONCLUSION: Cystoprostatectomy followed
      by immediate hormone therapy may be a feasible treatment option to achieve
      excellent local control for patients with previously untreated PCa, even in the
      presence of pelvic lymph node metastasis.

PMID- 19752607
TI  - Correlation between upgrading of prostate biopsy and biochemical failure and
      unfavorable pathology after radical prostatectomy.
AB  - OBJECTIVE: To evaluate whether upgrading of the biopsy after radical
      prostatectomy (RP) affects disease outcome in terms of unfavorable pathology and
      biochemical failure. PATIENTS AND METHODS: We retrospectively evaluated the
      records of 174 patients who underwent RP. Prostate biopsy and RP specimen Gleason
      scores (GSs) and correlative clinical data were recorded, and a multivariate
      analysis was applied. RESULTS: Overall (138 patients), the disease of 69 men
      (50.0%) was upgraded, in 19 (13.8%) it was downgraded, and in 50 (36.2%) it had
      an identical biopsy and pathological GS. Accuracy rates were significantly higher
      for GS 8-10 compared to low GSs, with a concordance of 50.0 and 12.2%,
      respectively (p < 0.01). Multivariate analysis revealed the single independent
      prognostic factor for a non-organ-confined disease as a RP GS 8-10 (p = 0.035).
      The factors associated with a positive surgical margin were a biopsy GS 8-10 (p <
      0.001) and the presence of biopsy score upgrading (p = 0.02). Biopsy GS >or=8 (p
      < 0.001) and presence of biopsy score upgrading (p = 0.009) were the two
      independent predictors of relapse after RP. CONCLUSION: This study demonstrated
      that biopsy upgrading was present in almost half of the patients who underwent RP
      and it was significantly related to positive surgical margins and biochemical
      relapse after RP.

PMID- 19752608
TI  - Topical and long-acting local anesthetic for prostate biopsy: a prospective
      randomized placebo-controlled study.
AB  - OBJECTIVE: To determine the efficacy of intrarectal lidocaine gel alone and a
      combination of lidocaine gel with 2 different longer-acting local anesthetic (LA)
      agents that were injected into the periprostatic area before transrectal
      ultrasound-guided prostate biopsy. PATIENTS AND METHODS: One hundred patients
      undergoing transrectal prostate biopsy were randomized into 4 groups of 25
      patients each. Before the biopsy, group 1 received no local anesthesia, group 2
      received 2% lidocaine gel intrarectally, group 3 received intrarectal lidocaine
      gel and 5 ml bupivacaine (0.25%) injected into periprostatic area, and group 4
      received lidocaine gel intrarectally and a 5-ml ropivacaine injection (0.25%) in
      the same location as group 3. Pain levels during and after the biopsy were
      assessed by using a 10-point linear visual analog scale (VAS). RESULTS: Patients
      in groups 3 and 4 had significantly lower VAS scores than those in groups 1 and
      2, both during and 1 h after biopsy. There were no differences in the pain scores
      between groups 1 and 2. CONCLUSION: The combination of intrarectal lidocaine gel
      and periprostatic longer-acting LA agents significantly reduces the pain related
      to prostate biopsy, whereas intrarectal lidocaine gel administration alone does
      not reduce pain. Thus, administration of the periprostatic longer-acting LA
      agents alone is adequate.

PMID- 19752609
TI  - A prospective randomised trial of extended core prostate biopsy protocols
      utilizing 12 versus 15 cores.
AB  - OBJECTIVE: To prospectively evaluate the diagnostic yield of 12 versus 15 core
      ultrasound-guided needle prostate biopsy protocol for detection of prostate
      cancer. PATIENTS AND METHODS: 244 patients were prospectively randomized to
      undergo 12 (group A), or 15 (group B) biopsies. The cancer detection rate was
      compared between these groups and within group B. RESULTS: There were no
      differences in the age, PSA, prostate volume or Gleason score of diagnosed
      cancers between groups. 113 (46%) of all patients were found to have carcinoma.
      The number of cancers diagnosed in each group was: 63 (51.6%) in group A, and 50
      (41.0%) in group B. In both groups, performing 12 biopsies increased the number
      of cancer cases identified by around 10% compared to 6. The frequency of cancer
      cases increased when 15 biopsies were performed, but not significantly (1.7%).
      The probability of finding a cancer after 12 biopsies was the same as after 15
      biopsies (p = 0.125, McNemar's test). CONCLUSIONS: There was no advantage in
      increasing the number of biopsy cores from 12 to 15 for the diagnosis of prostate
      cancer in men with an elevated PSA but normal digital rectal examination.

PMID- 19752610
TI  - Percentage of positive biopsy cores at the onset of hormone therapy for prostate
      cancer: prognostic significance.
AB  - INTRODUCTION: The percentage of positive prostate biopsy cores (%PBC) has been
      shown to be a prognostic factor in localized prostate cancer. We hypothesized
      that it would predict time to hormonal independence and survival in prostate
      cancer patients treated with androgen deprivation therapy (ADT). PATIENTS AND
      METHODS: We used clinical data from 403 men treated with ADT between 1980 and
      1999 and focused on a subgroup of 220 patients treated with GnRH analogue. %PBC
      was defined as the number of positive biopsy cores multiplied by 100 and divided
      by the total number of biopsy cores. RESULTS: Median %PBC was 83.3% (16.7-100%).
      Mean follow-up was 57.4 months. Survival at 5 years in men with 83.3% PBC or less
      was 62.3, 89.1 and 82.6% for recurrence-free, specific and overall survival,
      respectively, significantly better than that of men with a %PBC of more than
      83.3% (32.2, 74.7 and 67.7%, respectively; p < 0.004). Among the factors
      available in the pretreatment setting, namely age, clinical stage, PSA, Gleason
      score, bone scan and %PBC, the latter was independently associated with survival
      in multivariate analysis. CONCLUSIONS: %PBC may improve the ability to predict
      time to hormonal resistance and survival in patients treated with ADT for
      prostate cancer. This finding warrants further investigation.

PMID- 19752611
TI  - Health-related quality of life of prostate cancer patients compared to the
      general German population: age-specific results.
AB  - OBJECTIVE: The objective of this study was to examine the age-specific health
      related quality of life (HRQOL) of prostate cancer patients (PCPs). PATIENTS AND
      METHODS: 387 PCPs were asked to self-assess their HRQOL with the EORTC QLQ-C30
      questionnaire. Patients' data were compared with those of the general German
      population. RESULTS: The reported global health/QOL scores of the study group and
      the general German population are nearly equal. However, most of the subdomains
      of HRQOL are negatively affected in PCPs, especially in younger patients (<or=59
      years). CONCLUSION: Medical professionals should pay more attention to the
      emotional burden of PCPs, because their stress and strains during the time before
      treatment have a rather more emotional than physical character.

PMID- 19752612
TI  - Incidence and factors predicting the detection of prostate cancer after
      transurethral resection of the prostate for clinically benign disease.
AB  - INTRODUCTION: Transurethral resection of the prostate (TURP) is commonly
      performed as the surgical management of lower urinary tract symptoms due to
      clinically benign disease. However, prostate cancer is not uncommonly diagnosed
      after such a procedure. We, therefore, determined in a retrospective study the
      incidence and factors that might predict the detection of prostate cancer after
      TURP. PATIENTS AND METHODS: Between June 2005 and June 2007, a total of 476 men
      underwent TURP at our department. Of these, 411 men (86%) were thought to have
      benign disease and were included in the study. Univariate and multivariate
      logistic regression analyses using age, serum prostate-specific antigen (PSA),
      urinary retention status, prostate resection weight, FBC and U&E were performed
      to determine whether prostate cancer could be predicted. RESULTS: A total of 47
      men (11.4%) were diagnosed with prostate cancer [24/47 with pT1a (51%) and 23/47
      with pT1b (49%)]. Furthermore, the Gleason scores ranged from 5 to 9. Univariate
      logistic regression analyses revealed that only age (mean: 76 years, range: 54-90
      vs. mean: 71 years, range: 49-91 for prostate cancer and non-cancer cases,
      respectively) and serum PSA (mean: 14.9 ng/ml, range: 0.4-78.0 vs. mean: 7.4
      ng/ml, range: 0.2-90.0 for prostate cancer cases and non-cancer cases,
      respectively) were able to distinguish between cancer and non-cancer cases. In
      addition, using multivariate logistic regression, age and serum PSA were also the
      only variables that separated the two groups with a ROC-AUC of 70%. CONCLUSIONS:
      Our retrospective study has demonstrated that a substantial percentage of men are
      unexpectedly found to have prostate cancer after TURP. In addition, age and serum
      PSA were independent predictors of those who are likely to have prostate cancer.

PMID- 19752613
TI  - Hounsfield units on computed tomography predict calcium stone subtype
      composition.
AB  - INTRODUCTION: Hounsfield unit (HU) determination of urinary stones on noncontrast
      computed tomography (NCCT) has been shown to predict stone composition. However,
      no in vivo studies have attempted to radiographically separate the various
      calcium stone compositions. We investigate the efficacy of HU measurement on NCCT
      to determine if it can differentiate the various calcium stone subtypes. PATIENTS
      AND METHODS: Of the 684 patients who had undergone ureteroscopy at our
      institution from 1/2003 to 10/2007, 100 were identified with a documented NCCT, a
      chemical stone analysis and a stone size >5 mm but <2 cm. RESULTS: Stone
      compositions were categorized as 100-80% calcium oxalate monohydrate (CaOMH) (n =
      24), <80-60% CaOMH (n = 21), <60-50% CaOMH (n = 11) calcium oxalate dihydrate
      (CaODH) (n = 16), apatite (n = 9), brushite (n = 4), cystine (n = 2) and uric
      acid (n = 13). Mean HU were 879 +/- 230, 769 +/- 295, 717 +/- 304, and 517 +/-
      203 for the 100-80% CaOMH, <80-60% CaOMH, <60-50% CaOMH and CaODH groups,
      respectively. The average HU for the apatite, brushite, cystine and uric acid
      groups were 844 +/- 346, 1,123 +/- 254, 550 +/- 74 and 338 +/- 145, respectively.
      The CaOMH groups together had a significantly higher HU than the CaODH group (p <
      0.05) and a significantly lower HU than the brushite group (p < 0.05).
      CONCLUSIONS: HU measurement of urinary stones on NCCT may be used to separate
      some calcium stone subtypes, specifically CaOMH and CaODH. This information may
      be useful in counseling patients on treatment options for patients requiring
      intervention.

PMID- 19752614
TI  - Prospective questionnaire-based evaluation of the prevalence of urinary
      incontinence in women with chronic cough.
AB  - PURPOSE: Because chronic cough leads to repeated increases in intra-abdominal
      pressure, it might cause or unmask stress urinary incontinence (SUI). To test
      this hypothesis, we performed a cross-sectional prospective survey of women with
      chronic cough and female subjects without cough symptoms. METHODS: A group of
      women with chronic cough (n = 297) presenting at a specialty asthma/allergy
      clinic over an 18-month period and a control group (n = 106) completed a self
      administered survey that included the Urogenital Distress Inventory (UDI)-6
      questionnaire and a global quality of life (QOL) question. Subjects on medication
      for bladder symptoms (n = 14) or who had undergone prior anti-incontinence
      surgery (n = 29) were excluded. RESULTS: 263 patients and 97 control subjects met
      criteria for analysis. Chronic cough patients were older than control subjects
      (median 41 versus 35 years; p < 0.001). There was no difference in weight between
      groups (p = 0.544). The UDI-6 question responses correlated with each other and
      with the responses to the QOL questions (p values <or=0.002). Chronic cough
      patients were more bothered by urinary frequency (UDI question 1, 33 vs. 20%, p =
      0.018), sense of incomplete emptying (UDI question 5, 10 vs. 3%, p = 0.047).
      There was no statistical difference in SUI between chronic cough patients and
      controls (UDI question 3, 24 vs. 15%, p = 0.059). CONCLUSIONS: Based on this
      exploratory study, we found no statistically significant difference in the
      prevalence of SUI between patients with or without chronic cough. However,
      increased urinary frequency may have had a protective effect on SUI, thereby
      masking a larger difference in SUI.

PMID- 19752615
TI  - The incontinence impact questionnaire: results in an Italian female population
      stratified by educational status.
AB  - OBJECTIVE: To determine the response rate to the self-administered Incontinence
      Impact Questionnaire (IIQ) in an Italian female population. PATIENTS AND METHODS:
      172 consecutive patients referred to the urogynecological department of an urban
      university teaching hospital were invited to answer the self-administered IIQ.
      Correlations were investigated between answer rate, age, educational status and
      urogenital pathology. RESULTS: Only 41.6% of patients with low educational status
      answered all questions compared with 47.6 and 58% of medium and high educational
      status (p = 0.038 and p = 0.011 respectively). Mean patient age correlated
      inversely with educational status (rho = -0.443; p < 0.0001) and directly with
      non-response rate (rho = 0.207; p = 0.007). The non-response rate was correlated
      significantly and inversely with educational status only in continent patients
      (rho = -0.254; p = 0.037) and in patients with pelvic organ prolapse (rho = 
      0.256; p = 0.017). CONCLUSIONS: The IIQ answer rate correlated directly with
      educational status in an Italian female population.

PMID- 19752616
TI  - Statistical analysis of symptoms, endoscopy and urothelial morphology in 58
      female bladder pain syndrome/interstitial cystitis patients.
AB  - INTRODUCTION: The goal of the study was to assess the course of painful syndrome
      in patients with bladder pain syndrome/interstitial cystitis and to assess the
      changes in endoscopic and histopathological findings in relation to the type of
      treatment. PATIENTS AND METHODS: We included a total of 58 patients with
      histologically diagnosed interstitial cystitis. Out of these, 31 patients were
      treated with oral pharmacotherapy and 27 patients were treated by intravesical
      application of heparin. The patients were followed from time of diagnosis for 6.9
      +/- 2.5 and 6.6 +/- 2.7 years, respectively. RESULTS: Treatment - irrespective of
      its type - had a clear demonstrable effect on the monitored parameters;
      intravesical treatment was more effective than oral. Statistically significant (p
      < 0.05) changes could be observed in both groups (with two exceptions). When
      evaluating the relationship between subjective symptoms and objective criteria,
      and patients' age and time to diagnosis, it is clear that the higher the age and
      the longer the time from symptoms to diagnosis, the more severe the symptoms.
      CONCLUSIONS: When evaluating the monitored parameters, we found significant
      correlations (both positive and negative). However, these relationships cannot be
      used to simplify the evaluation algorithm (according to ESSIC) and the initial
      criteria cannot predict the course of the disease.

PMID- 19752617
TI  - De novo urothelial carcinoma in kidney transplantation patients with end-stage
      aristolochic acid nephropathy in China.
AB  - INTRODUCTION: Aristolochic acid contained in Chinese herbs has been proved to be
      nephrotoxic and carcinogenic. Immunosuppression is associated with an increased
      risk of developing malignancies. What will be the result if these two significant
      risk factors are concomitantly present in transplanted patients with aristolochic
      acid nephropathy (AAN)? PATIENTS AND METHODS: A 2-center cohort of 1,612 renal
      transplant recipients was studied retrospectively from January 1998 to December
      2006. We performed an evaluation of the database and review of the charts and
      pathology reports of these recipients. RESULTS: Kidney transplantations were
      performed in 17 patients with AAN. Nine (52.9%) of these recipients developed
      urothelial carcinoma (UC), compared with a 0.46% prevalence of urinary tract
      tumors among kidney-transplanted patients in China. Eight cases (88.9%) involved
      the upper urinary tract (bilateral, 3 cases, 37.5%; unilateral, 5 cases, 62.5%).
      All patients underwent surgical treatment. Six patients (75%) had recurrence
      during the follow-up period. Three patients died within a mean of 20 months after
      tumor excision. CONCLUSIONS: The risk for UC is distinctly increased in patients
      with AAN after transplantation. Regular screening for early detection of
      malignancy is mandatory.

PMID- 19752618
TI  - 'Evaluation of Residencies' in Turkey. The first report of the ESRU questionnaire
      in the Europe 'home version'.
AB  - INTRODUCTION: We aimed to evaluate the general status of last-year residents in
      Turkey by filling in the questionnaire 'Evaluation of Residencies in Europe'.
      SUBJECTS AND METHODS: The questionnaire 'Evaluation of Residencies in Europe',
      designed by the European Society of Residents in Urology (ESRU), was applied to
      91 last-year urology residents. It consisted of 7 sections; 'Introduction',
      'Membership', 'Residency', 'Life and Financial Conditions', 'Future Practice',
      'Training' and 'Research Activities and Contribution to Scientific Literature'.
      The results were determined and reviewed as well. Statistical analysis was
      performed using ANOVA and the Kruskal-Wallis Test. RESULTS: More than 40
      parameters were evaluated. The level of English was average or good for 86%. Half
      of the residents were aware of ESRU activities, 91% knew national ESRU
      representatives. Fifty-seven percent of the residents wanted to subspecialize in
      urology, nephrectomy or andrology, and general urology procedures had a high rate
      being performed by a first surgeon. Transurethral prostate resection,
      transurethral resection of bladder and extracorporeal shock wave lithotripsy were
      well known, with a rate of 76%. CONCLUSIONS: Although the Turkish resident number
      is one of the most excessive in Europe, we have a well-trained homogenous
      resident group especially in the field of endourology; most of those in the last
      year of their training period were satisfied with their general condition.

PMID- 19752619
TI  - Inversion, hydration and diuresis during extracorporeal shock wave lithotripsy:
      does it improve the stone-free rate for lower pole stone clearance?
AB  - OBJECTIVE: It was the aim of this study to assess the efficacy and safety of
      combined forced hydration and diuresis with limited inversion during shock wave
      lithotripsy (SWL) by comparing this treatment modality with conventional SWL for
      lower calyceal nephrolithiasis. PATIENTS AND METHODS: In this prospective, non
      randomized study, we included 100 patients with lower calyceal calculi <or=2 cm.
      Fifty of them received conventional SWL and the other 50 underwent SWL combined
      with oral hydration, diuresis and 12 degrees inversion position during SWL.
      Intravenous urography was performed for all patients prior to their treatment.
      Patients in both groups were treated on Dornier MPL 9000. Blood pressure
      monitoring was applied during the SWL session. Follow-up was performed the first
      and the third month after treatment with plain kidney-ureter-bladder X-ray and
      kidney-ureter-bladder ultrasound. RESULTS: Clinical outcomes were available in 90
      patients. Follow-up at 3 months showed that 83.3% of the patients belonging to
      the study group were rendered stone free, whereas 71.5% were stone free in the
      control (p > 0.05). Complications were minimal and not statistically significant.
      CONCLUSIONS: Forced diuresis and inversion therapy is very well tolerated;
      however, the stone-free rate was not significantly improved.

PMID- 19752620
TI  - Clinical and demographic characteristics of children with urolithiasis: single
      center experience from eastern Turkey.
AB  - OBJECTIVE: To evaluate the clinical and demographic findings of children with
      urolithiasis in eastern Turkey. METHODS: We retrospectively reviewed the medical
      records of 67 children with urolithiasis for clinical and laboratory data.
      RESULTS: Mean age at the time of diagnosis was 39.1 +/- 41.2 months. Complaints
      at admission were: urinary tract infection (29.9%), macroscopic hematuria
      (26.9%), abdominal or flank pain (19.4%), spontaneous passing of the stone
      (8.9%), growth and developmental delay (7.5%), and non-specific findings (8.9%).
      A family history of urolithiasis was positive in 50.7% of patients. Metabolic
      screening could be performed in 47 (70.1%) of patients due to socioeconomic
      problems and revealed hypercalciuria in 59.6%, infectious stone in 17%,
      cystinuria in 6.4%, hyperuricosuria in 10.6%, hyperoxaluria 4.3%, and
      hypocitruria in 2.1%. Stone analysis of patients (26.9%) revealed calcium oxalate
      in 38.9%, calcium phosphate in 22.2%, uric acid in 16.7%, cystine in 11.2%,
      struvite in 5.6% and mixed content in 5.6%. CONCLUSION: We believe early
      diagnosis with detailed metabolic screening and appropriate treatment and follow
      up procedures and the contribution of urolithiasis to end-stage renal disease can
      be avoided.

PMID- 19752621
TI  - Does ureteral stenting prior to shock wave lithotripsy influence the need for
      intervention in steinstrasse and related complications?
AB  - OBJECTIVE: To analyze factors affecting steinstrasse (SS) and study the impact of
      pre-shock wave lithotripsy (SWL) stenting in the prevention of SS and related
      complications. PATIENTS AND METHODS: The cohort included 4,644 patients with
      renal stones treated by SWL. Three hundred and twenty-six (7%) developed SS.
      Initially, all patients were managed conservatively (group 1); interventions were
      reserved for those in whom conservative treatment failed (group 2). The 2 groups
      were further analyzed to identify factors influencing the need for intervention.
      The impact of pre-SWL stenting on the development of SS and the need for
      intervention was also assessed. RESULTS: Expectant management was successful in
      176 (54%) patients, while 150 (46%) required intervention for SS. The size of the
      stones had a significant association with the number of sessions required (p <
      0.01) and the development of SS. The placement of a stent prior to SWL decreased
      neither the sessions of SWL (p < 0.01) nor the interventions required for SS and
      related complications. CONCLUSIONS: SWL for larger stones is a potentially
      significant complication of SWL and is associated with significant morbidity.
      Ureteral stents decrease the acute presentations of patients with SS; however, it
      does not decrease the ultimate need for intervention in the management of SS.

PMID- 19752622
TI  - Alendronate reduces the excretion of risk factors for calcium phosphate stone
      formation in postmenopausal women with osteoporosis.
AB  - OBJECTIVE: Osteoporosis is associated with the pathogenesis and risk of
      urolithiasis, which is higher among postmenopausal women (as opposed to
      premenopausal). Bisphosphonates potently inhibit bone resorption, and are used in
      the management of bone disease. We investigated the ability of a bisphosphonate
      to prevent calcium stone formation. METHODS: We studied 12 postmenopausal women
      (63.8 +/- 7.3 years) who were not receiving osteoporosis therapy, and had stones
      comprised of calcium phosphate (CaP; n = 3), calcium oxalate (CaOx; n = 3) and
      CaP + CaOx (n = 6). We measured bone mineral density (BMD), serum and urinary
      values in 24-hour urine specimens before and 3 months after the oral
      administration of 5 mg/day of alendronate (ALN). The indexes of the ionic
      activity product of calcium oxalate, AP(CaOx), and of calcium phosphate, AP(CaP),
      were estimated using the Tiselius method. RESULTS: ALN significantly reduced the
      AP(CaP) index (1.53 +/- 1.37 to 0.89 +/- 0.81, p <0.05). Urinary calcium,
      oxalate, phosphate and the AP(CaOx) index did not significantly change. BMD
      improved in 11 of the 12 patients. Urinary stones did not develop in any of the
      patients during the course of the study. CONCLUSION: The results suggested that
      ALN not only improves BMD and osteoporosis, but also reduces the risk of calcium
      phosphate stone formation in postmenopausal women.

PMID- 19752623
TI  - Sympathetic nervous system overactivity in the Wistar rat with proliferative
      lesions of ventral prostate induced by chronic stress.
AB  - OBJECTIVES: The sympathetic nervous system and hypothalamic-pituitary-adrenal
      axis have been known to be reactive to psychological factors such as stress in
      which several humoral factors are released. Growing data suggest that stress
      conditions could be associated with the development or aggravation of prostatic
      disease. The present study aims to investigate the influence of chronic stress
      and blockade of the sympathetic nerve on rat prostate. METHODS: We used 2 weeks
      of restraint water-immersion stress to induce a chronic psychological stress
      model of Wistar rats. Denervation of the peripheral sympathetic nerve was done by
      6-hydroxydopamine (6-OHDA). Blood flow of ventral prostate, plasma catecholamine
      and cortisol were measured at the end of the experiment. The weight and
      secretions of dissected prostate lobes were measured and histology was performed
      by hematoxylin and eosin stain. RESULTS: After 14 days of stress, the blood flow
      of ventral prostate decreased and plasma cortisol increased. The apparent
      proliferation of epithelium of ventral lobes were observed and dorsolateral ones
      were almost unaffected. On the other hand, the hyperplasia changes were not seen
      after the chemical sympathectomy had been done during stress. CONCLUSIONS:
      Chronic stress may lead to hyperplasia of ventral prostate, the overactivity of
      sympathetic nervous system is involved in the pathogenesis of prostatic disease.

PMID- 19752624
TI  - Pure primary prostatic osteosarcoma arising in a non-irradiated prostate.
AB  - A 68-year-old man who initially presented with hematuria was found on prostate
      biopsy to have sarcoma of the prostate with osteogenic features. Radiological
      examination revealed a locally advanced pelvic mass involving the prostate,
      seminal vesicles, and rectal wall without metastatic disease. The patient
      underwent total pelvic exenteration with intraoperative radiotherapy. The tumor
      was composed of two nodules measuring 7.5 and 4.5 cm involving the prostate, both
      seminal vesicles, the bladder, rectum, and perirectal fibroadipose tissue. The
      final diagnosis was osteogenic sarcoma of the prostate.

PMID- 19752625
TI  - Recurrence of renal cell carcinoma in a renal allograft after partial transplant
      nephrectomy: a case report.
AB  - Treatment options for renal cell carcinoma (RCC) in a renal allograft include
      radical nephrectomy or nephron-sparing surgery (NSS). We report the case of local
      recurrence of an RCC in kidney allograft. Five years after previously undergoing
      NSS, a recurrent lesion was diagnosed in the upper pole of the kidney graft in a
      74-year-old patient during routine duplex ultrasonography. The computerized
      tomography image showed a spherical lesion of 24 mm in diameter. The patient was
      free of clinical symptoms and additional staging examinations showed no signs of
      metastatic spread. Considering the poor function of the kidney allograft with the
      need for dialysis, a removal of the graft was performed without peri- and
      postoperative adverse events. The final pathology revealed recurrence of a clear
      cell adenocarcinoma of the kidney allograft (pT1a, G1). The patient had an
      uneventful recovery and was discharged from the hospital after 6 days. During the
      last follow-up, the patient remained stable on hemodialysis and reported good
      overall health condition. In conclusion, patients after NSS for small renal
      masses in kidney allograft should remain under careful observation in order to
      detect early local recurrence.

PMID- 19752626
TI  - Simultaneous occurrence of renal oncocytoma and B small cell lymphoma in the same
      kidney: report of two cases.
AB  - Two cases of simultaneous occurrence of oncocytoma (OC) associated with small B
      cell lymphoma in the same kidney were investigated. Computed tomography,
      performed for staging purposes, incidentally revealed a small hypo- and
      hyperattenuating renal mass. Diagnosis of OC was performed on the specimen by
      morphology, immunohistochemistry and electron microscopy. The patients are in
      complete remission after a vaccinotherapy with follicular dendritic cells. The
      occurrence of OC and non-Hodgkin lymphoma in the same kidney has never been
      reported. These case reports outline that computerized tomography is a sensitive
      method in the staging of lymphoma. However, when some solid, small hyper- or
      hypoattenuating masses occur in the kidney, the diagnosis by computed tomography
      alone is always a challenge and other malignant neoplasms may be considered.
      Immunohistochemistry and electron microscopy allow a definitive diagnosis of OC.

PMID- 19752627
TI  - Misleading abdominal pain following extracorporeal renal lithotripsy.
AB  - INTRODUCTION: Extracorporeal shockwave lithotripsy (ESWL) is a useful technique
      for the treatment of kidney and urinary tract stones but appears also to cause
      some extrarenal complications. CASE PRESENTATION: We report the case of a 33-year
      old Caucasian man with a history of Crohn's disease who presented septic shock
      due to a jejunum perforation 6 h following an ESWL for a right ureteral stone.
      The perforation, which occurred at the exact site of a previous surgical
      anastomosis, was revealed on a CT scan which found an unusual aspect probably due
      to cavitation and bubbles formation induced by ESWL. CONCLUSION: This case
      emphasizes the particular aspect of CT scan and the extrarenal potential danger
      of the ESWL procedure. Some precautions and dedicated patient information must be
      taken when used in patients with chronic inflammation of the digestive tract or
      history of intestinal surgery.

PMID- 19752630
TI  - The expansion of faith-based partnerships with government.
AB  - Social service partnerships between faith-based organizations and federal, state,
      and local government have been established for several decades; however, they
      have experienced significant expansion and increased support in recent years.
      These partnerships have long centered on helping individuals cope with issues of
      substance abuse and mental health, as well as overcoming other addictive
      behaviors, and establishing positive life practices for self-sufficiency. These
      partnerships are rather old in nature but relatively new in scope and focus
      bringing a myriad of resources into the public square as well as opportunities
      for additional research on their efficacy.

PMID- 19752631
TI  - Faith-based organization welcomes women back home into the community: changing
      lives, restoring families, and building community.
AB  - This article reviews the current research related to the many issues affecting
      women's journey from incarceration back into community living. The complex
      transition process that comes when ex-offenders attempt to reenter society post
      release is examined, and the story of one faith-based community reentry program
      for women located in southern California is described. The women in this program
      currently achieve overall recidivism rates of 3% as compared with national
      averages of 50%. The program uses peers to help newly released women achieve long
      term success. The specific steps taken by this organization to obtain such
      significant measurable positive outcomes are described.

PMID- 19752632
TI  - A peer-driven mentoring case management community reentry model: an application
      for jails and prisons.
AB  - Welcome Home Ministries (WHM) is a peer-driven reentry program for women
      reentering the community from jail and prison. One of the major contributing
      factors to a high recidivism rate is the presenting issue of co-occurring
      disorders stemming from early childhood abuse and trauma found in 85% of the
      women seeking the assistance of WHM. The peers within WHM, having experienced
      mental health issues, substance abuse, and incarceration themselves, identified
      and developed a specific reentry program for this population. This article
      presents the results of a yearlong study that addresses the following: (1) the
      issue of co-occurring disorders; (2) the impact of early childhood trauma and
      abuse on the rate of incarceration; (3) the outcomes for restoration and
      recovery; and (4) the desire of the women to give back to the community.

PMID- 19752633
TI  - Faith-based programs and their influence on homelessness.
AB  - In America today, homelessness is coming under increasing pressure by federal,
      state, local, and faith-based providers of prevention and intervention services.
      American philanthropy makes a response to this pervasive problem possible through
      faith-based institutional and local efforts that facilitate the effectiveness of
      governmental programs designed to eliminate long-term homelessness by 2014. Faith
      based providers of services are on the front line of efforts to wrap services
      around willing participants who build or rebuild effective social and
      instrumental resources. Most homelessness is temporary and even long-term
      homelessness often responds to supportive services delivered in a stable housing
      environment.

PMID- 19752634
TI  - Pragmatic action research with 2 vulnerable populations: Mexican American elders
      and formerly incarcerated women.
AB  - Eliminating health disparities involving minority groups is a major national
      priority. Action research, a response to this national priority, may be derived
      from different theoretical models. The purposes of action research are to involve
      key community stakeholders in developing knowledge and taking pragmatic action to
      solve problems. In this article, the authors examine how the model was put into
      action for 2 distinct programs of research, comparing and contrasting final
      results, one report primarily focusing on recruitment and retention of
      participants and the other focusing on a community faith-based action research
      with formerly incarcerated women.

PMID- 19752635
TI  - Faith community nursing demonstrates good stewardship of community benefit
      dollars through cost savings and cost avoidance.
AB  - Health systems seeking responsible stewardship of community benefit dollars
      supporting Faith Community Nursing Networks require demonstration of positive
      measurable health outcomes. Faith Community Nurses (FCNs) answer the call for
      measurable outcomes by documenting cost savings and cost avoidances to families,
      communities, and health systems associated with their interventions. Using a
      spreadsheet tool based on Medicare reimbursements and diagnostic-related
      groupings, 3 networks of FCNs have together shown more than 600 000 (for calendar
      year 2008) healthcare dollars saved by avoidance of unnecessary acute care visits
      and extended care placements. The cost-benefit ratio of support dollars to cost
      savings and cost avoidance demonstrates that support of FCNs is good stewardship
      of community benefit dollars.

PMID- 19752636
TI  - Making a difference: initiating and maintaining a faith-based free health clinic.
AB  - This article is a summary of the challenges, struggles, and barriers that a group
      of churches encountered in developing a faith-based free health clinic. From the
      inception, this clinic has existed for the uninsured whose total household income
      aligns with the 2009 Fedral Poverty Guidelines. A voluntary interview with the
      executive director of The Good Samaritan Clinic revealed the experiential
      evolvement of this free health clinic. Numerous examples are shared that depict
      how this clinic has made a difference in the lives of many people.

PMID- 19752637
TI  - A spiritually based caregiver intervention with telephone delivery for family
      caregivers of veterans with dementia.
AB  - Caring for veterans with dementia is burdensome for family caregivers. This
      exploratory study tested the efficacy of an innovative, spiritually based mantram
      caregiver intervention delivered using teleconference calls. A prospective,
      within-subjects, mixed-methods, and 3-time repeated-measures design with 36-week
      follow-up telephone interviews was conducted. Sixteen caregivers (94% women, 94%
      Whites with mean age 69.2 years, SD = 10.35 years) completed the intervention.
      Significant effects for time and linear terms were found for decreasing caregiver
      burden, perceived stress, depression, and rumination and for increasing quality
      of life enjoyment and satisfaction, all with large effect sizes. Findings suggest
      that teleconference delivery of a spiritually based caregiver intervention is
      feasible.

PMID- 19752638
TI  - Family traditions and generations.
AB  - Currently, traditional family values that have been passed down through
      generations appear to be at risk. This has significant implications for the
      stability and health of individuals, families, and communities. This article
      explores selected issues related to intergenerational transmission of family
      values and cultural beliefs, with particular reference to Western culture and
      values that are rooted in Jewish and Christian traditions. It also examines
      family values and parenting styles as they influence the developing perspective
      of children and the family's adaptation to a changing world.

PMID- 19752639
TI  - Barriers to the use of genetic testing: a study of racial and ethnic disparities.
AB  - PURPOSE: Racial and ethnic disparities in health are evident among a range of
      diseases and health care services. New genetic technologies are likely to
      increase these disparities as access to expensive genetic tests further widens
      the gap. METHODS: Our analysis used data from a national representative sample
      collected in 2000. The total sample size for our analysis was 1724 men and women
      (consisting of 946 non-Hispanic whites, 392 Latinos, and 386 blacks) aged 18 to
      91 years. Ordered logistic regression and binary logistic regression analysis
      were applied to investigate differences by race/ethnicity. RESULTS: Results
      showed significant differences by racial/ethnic groups in knowledge and concerns
      about the potential misuse of genetic testing. A significant difference was also
      found between the types of health insurance coverage by race/ethnicity as well as
      significantly higher levels of mistrust in a physician and the medical system.
      CONCLUSION: Our findings raise concern about several barriers among minorities
      and calls for a development of educational and communication strategies that
      facilitate in narrowing the gap between racial and ethnic groups.

PMID- 19752640
TI  - Reply to letter from Drs. Ledbetter, Saul, and Moeschler.

PMID- 19752641
TI  - Comments on the "genotype first diagnosis" controversy.

PMID- 19752642
TI  - The interplay of perceived social support and posttraumatic psychological
      distress following orofacial injury.
AB  - Social support is believed to mediate psychosocial recovery in vulnerable
      populations after trauma. In this study, we examine the relationships between
      perceived social support and posttraumatic stress disorder symptoms in a cohort
      of 287 socio-economically disadvantaged adults with orofacial injury, using 3
      waves of data collected over a period of 1 year after the injury. Using
      structural equation modeling process, we evaluated the cross-lagged effects
      between perceived social support (PSS) and posttraumatic stress disorder (PTSD)
      symptoms. We found that PSS had a direct influence on PTSD only when examined
      concurrently. After controlling the covariates, the model supports the cross
      lagged effect for PTSD symptoms on PSS at T2 and T3, which suggests a reciprocal
      contribution between symptoms and support as time progressed. Our data suggest
      that, over time, high rates of PTSD symptoms are related to a diminished
      perception of available social support.

PMID- 19752643
TI  - A review of dissociative disorders treatment studies.
AB  - This review examines empirical reports of treatment for Dissociative Disorders
      (DD), including 16 DD treatment outcome studies and 4 case studies that used
      standardized measures. Collectively, these reports suggest that treatment for DD
      is associated with decreased symptoms of dissociation, depression, posttraumatic
      stress disorder, distress, and suicidality. Effect sizes, based on pre/post
      measures, are in the medium to large range across studies. Patients with
      dissociative disorder who integrated their dissociated self states were found to
      have reduced symptomatology compared with those who did not integrate. The
      magnitude of pre/post effect sizes for these DD studies are comparable to
      pre/post effect sizes in treatment studies of complex PTSD. There are significant
      methodological limitations in the current DD treatment outcome literature that
      reduce internal and external validity including regression towards the mean,
      limited sample sizes, and nonrandomized research designs. Implications for future
      research and treatment planning for patients suffering from DD are discussed.

PMID- 19752644
TI  - Deficits in emotional awareness in schizophrenia and their relationship with
      other measures of functioning.
AB  - Conscious awareness of emotion is adaptive and its disruption in schizophrenia
      can impact social functioning. This study assessed levels of emotional awareness
      for self and others in social scenarios (Levels of Emotional Awareness Scale) in
      21 individuals with schizophrenia spectrum disorders (SSD) and 20 healthy
      individuals. Individuals with SSD had lower levels of emotional awareness for
      others in complex social scenarios, but not simple social scenarios; no
      difference was found in emotional awareness for self. Higher levels of emotional
      awareness were associated with better quality of life in patients. Patients also
      reported higher social anhedonia. Healthy individuals' higher levels of emotional
      awareness for self were associated with lower anhedonia, but this relationship
      was not found in SSD patients. Individuals with schizophrenia have particular
      difficulty anticipating others' emotional responses in complex social situations.
      Further, this deficit is independent of anhedonia in SSD patients, indicating a
      systemic disruption in the integration of emotional processing.

PMID- 19752645
TI  - Understanding the relationships between self-esteem, experiential avoidance, and
      paranoia: structural equation modelling and experience sampling studies.
AB  - Hypothesized relationships between experiential avoidance (EA), self-esteem, and
      paranoia were tested using structural equation modeling in a sample of student
      participants (N = 427). EA in everyday life was also investigated using the
      Experience Sampling Method in a subsample of students scoring high (N = 17) and
      low (N = 15) on paranoia. Results showed that paranoid students had lower self
      esteem and reported higher levels of EA than nonparanoid participants. The
      interactive influence of EA and stress predicted negative self-esteem: EA was
      particularly damaging at high levels of stress. Greater EA and higher social
      stress independently predicted lower positive self-esteem. Low positive self
      esteem predicted engagement in EA. A direct association between EA and paranoia
      was also found. These results suggest that similar mechanisms may underlie EA and
      thought suppression. Although people may employ EA to regulate self-esteem, this
      strategy is maladaptive as it damages self-esteem, incurs cognitive costs, and
      fosters paranoid thinking.

PMID- 19752646
TI  - Lack of association between neuropsychological performance and level of psychosis
      proneness in an adolescent psychiatric sample.
AB  - Studies of the prodromal stage of schizophrenia show that the late prepsychotic
      phase is associated with mild neuropsychological deficits that parallel those of
      schizophrenia. However, it is still unclear whether this association is present
      across the whole range of symptoms of psychosis-proneness, or specific to the
      extreme groups. In this study, the linear associations between dimensions of
      psychosis-proneness (as measured by the 92-item Prodromal Questionnaire) and
      performance on 20 neuropsychological measures were assessed in a group of 71
      nonpsychotic adolescent psychiatric patients. A structure of positive, negative
      and disorganized prodromal symptom dimensions was found, replicating earlier
      findings. No symptom dimension was significantly associated with
      neuropsychological performance, even when corrected for nonspecific psychological
      distress. These findings suggest that the association between symptoms and
      neuropsychological performance is specific to high levels of symptoms or to the
      truly prodromal subpopulation. The results also highlight the importance of
      simultaneous assessment of affective state.

PMID- 19752647
TI  - Specificities of defense mechanisms in bipolar affective disorder: relations with
      symptoms and therapeutic alliance.
AB  - Defense mechanisms as a central notion of psychoanalysis have inspired various
      levels of interest in research in psychotherapy and psychopathology. Defense
      specificities have only recently been investigated systematically with regard to
      several clinical diagnoses, such as affective and personality disorders. For the
      present study, 30 inpatients diagnosed with Bipolar Affective Disorder I (BD)
      were interviewed. An observer-rater method, the Defense Mechanisms Rating Scales
      (DMRS), applied to session-transcripts, of assessment of defenses was used. A
      matched, nonclinical control group was introduced. Defense specificities in BD
      encompass a set of 5 immature defenses, of which omnipotence is linked with
      symptom level. The level of the therapeutic alliance is predicted by mature
      defenses. These results are discussed with regard to the psychological
      vulnerability of BD, and treatment implications for psychodynamic psychotherapy
      with such challenging patients are evoked.

PMID- 19752648
TI  - Validity and reliability of the Hamilton depression rating scale (5 items) for
      manic and mixed bipolar disorders.
AB  - Depressive symptoms during mania have prognostic value in bipolar disorder. For
      depressive symptoms, it has been proposed that shorter scales should be cost
      effective and practical. To determine the usefulness of 5-item Hamilton
      Depression Rating Scale (HAMD-5) in manic and mixed bipolar disorder, we used a
      four-week follow-up prospective, observational study. Convergent and discriminant
      validity, internal consistency, and reliability were analyzed and compared with
      HAMD-21, HAMD-5, and HAMD-21 cut-off points were calculated versus CGI-BP. A
      total of 173 manic and mixed patients were evaluated. HAMD-5 showed appropriate
      convergent validity, discriminant validity, internal consistency, and test-retest
      reliability. Discriminant validity was higher for HAMD-5 than HAMD-21. Best cut
      off point of remission was: HAMD-21 < or =5 and HAMD-5 < or =1. HAMD-5 presents
      appropriate validity and reliability estimates. It is comparable to HAMD-21 and
      focuses more specifically on depressive symptoms.

PMID- 19752649
TI  - Personality subtypes of suicidal adults.
AB  - Research into personality factors related to suicidality suggests substantial
      variability among suicide attempters. A potentially useful approach that accounts
      for this complexity is personality subtyping. As part of a large sample looking
      at personality pathology, this study used Q-factor analysis to identify subtypes
      of 311 adult suicide attempters using Shedler-Westen Assessment Procedure-II
      personality profiles. Identified subtypes included internalizing, emotionally
      dysregulated, dependent, hostile-isolated, psychopathic, and anxious somatizing.
      Subtypes differed in hypothesized ways on criterion variables that address their
      construct validity, including adaptive functioning, Axis I and II comorbidity,
      and etiology-related variables (e.g., history of abuse). Furthermore, dimensional
      ratings of the subtypes predicted adaptive functioning above DSM-based diagnoses
      and symptoms.

PMID- 19752650
TI  - Perception that "everything requires a lot of effort": transcultural SCL-25 item
      validation.
AB  - This brief report illustrates how the migration context can affect specific item
      validity of mental health measures. The SCL-25 was administered to 432 recently
      settled immigrants (220 Haitian and 212 Arabs). We performed descriptive
      analyses, as well as Infit and Outfit statistics analyses using WINSTEPS Rasch
      Measurement Software based on Item Response Theory. The participants' comments
      about the item You feel everything requires a lot of effort in the SCL-25 were
      also qualitatively analyzed. Results revealed that the item You feel everything
      requires a lot of effort is an outlier and does not adjust in an expected and
      valid fashion with its cluster items, as it is over-endorsed by Haitian and Arab
      healthy participants. Our study thus shows that, in transcultural mental health
      research, the cultural and migratory contexts may interact and significantly
      influence the meaning of some symptom items and consequently, the validity of
      symptom scales.

PMID- 19752651
TI  - The challenges of ecological validity in the measurement of social perception in
      schizophrenia.
AB  - Ecological validity may be substantiated by verisimilitude (the stimuli and
      cognitive processing of a test resemble the stimuli and cognitive processing
      required in everyday life) and/or veridicality (a test is statistically
      associated with everyday life functioning). The Interpersonal Perception Task
      uses real-life social behavior as stimuli and has high verisimilitude. We
      examined the Interpersonal Perception Task-15 in 72 persons with schizophrenia
      and 58 healthy controls. The test discriminated well between groups, but failed
      to show associations with community functioning in participants with
      schizophrenia, indicating poor veridicality. This study shows that the 2
      approaches to ecological validity can dissociate. Hence, it is important for
      investigators to conduct psychometric investigations when borrowing measures from
      social psychology for schizophrenia research.

PMID- 19752652
TI  - Rumination and negative symptoms in schizophrenia.
AB  - Rumination is thought to be an important maintaining factor in depression.
      Depressive symptomatology is also a prominent feature in schizophrenia. However,
      little is known about the relationship between rumination and symptoms, such as
      depression and negative symptoms, in schizophrenia. The present study examined
      associations between rumination and symptoms in a group of 37 stable medicated
      patients with schizophrenia. All participants were clinically assessed on their
      symptoms and completed self-reported measures of depression and rumination. The
      findings showed that negative symptoms, especially emotional withdrawal and
      stereotyped thinking, but not depressive symptomatology, were associated with
      rumination in the present sample of patients with schizophrenia. If the findings
      are replicated, interventions that reduce rumination and rigid thinking might be
      helpful to reduce some negative symptoms of psychosis.

PMID- 19752653
TI  - Stressful life-events and fatigue in a nonclinical sample.
AB  - There is a lack of systematic examination of the relationship between different
      stressor features and fatigue. Thus, we examined which features of stressors
      (e.g. frequency, duration, severity, valence, type) were most strongly related to
      fatigue levels. Eighty-nine participants completed a short fatigue questionnaire
      and a comprehensive stress interview. High fatigue levels were found to be most
      strongly related to the number of acute interpersonal stressors and chronic
      difficulty stressors (<6 months duration) and psychological distress, but no
      other stressor measure. Thus, acute and chronic stressor frequency counts might
      be the best measures used in future studies assessing the relationship between
      stressors and fatigue.

PMID- 19752655
TI  - Data collection methods series. Part 5: Training for data collection.

PMID- 19752656
TI  - WOC nurse wound consult: negative pressure wound therapy.

PMID- 19752657
TI  - Efficacy of a skin tear education program: improving the knowledge of nurses
      practicing in acute care settings.
AB  - PURPOSE: We sought to evaluate the knowledge base of acute care registered nurses
      (RNs) regarding skin tears and the efficacy of an online educational program
      designed to improve their knowledge of skin tears including (1) predisposing
      factors; (2) identification and assessment of skin tears using the Payne-Martin
      Classification System; and (3) preventive care, treatment, and documentation.
      DESIGN: This was a prospective quasi-experimental education intervention study.
      PARTICIPANTS AND SETTING: Four hundred sixteen acute care RNs from 2 affiliated
      hospitals participated in the study. They comprised approximately 20% of more
      than 2,000 nurses employed by Atlantic Health. These nurses worked in critical
      care, medical-surgical, and specialty units and varied in age, level of
      education, work experience, and years in nursing. METHODS: A Web-based
      educational program was provided for over 4 months on our intranet service, which
      was available to all RN staff 24-hours-a-day, 7-days-a-week. The educational
      program was subdivided into 3 sections: (1) identification and assessment, (2)
      classification and differentiation, and (3) treatment. RESULTS: Nurses' knowledge
      of skin tears improved following the Web-based educational program. Following
      completion of the identification and assessment of skin tears section,
      participants were better able to identify and correctly assess skin tears (mean
      scores 99.1% vs 97.1%, P < .001). Participants also achieved greater knowledge of
      the differentiation between categories I, II, and III skin tears (mean scores
      94.9% vs 83.4%, P < .001) and knowledge of treatment (mean score 93.7% vs 73.8%,
      P < .001). CONCLUSION: Our Web-based skin tear educational program was effective
      in improving nurses' knowledge regarding skin tear identification and assessment,
      classification and differentiation, and treatment.

PMID- 19752658
TI  - Comparison of bodily pain: persons with and without venous ulcers in an indigent
      care clinic.
AB  - PURPOSE: The purpose of this study was to examine bodily pain and its
      relationship with functional status, perception of control, coping, and
      depression for patients with and without venous ulcers who were receiving care in
      an urban, primary care clinic for low-income adults. METHODS: We used an
      exploratory, cross-sectional design. Participants (N = 301) completed
      demographic, pain severity and pain interference with function, depression,
      control, and coping questionnaires. Seventy patients (23.3%) had venous ulcers
      and 231 (76.7%) did not. RESULTS: Participants were generally male (53%, n =
      159), mostly African American (92%, n = 277), and ranged in age from 22 to 74
      years (M = 49.5, SD = 8.5). Persons with and without venous ulcers did not differ
      significantly based on gender, race, number of pain sites (n = 3.3), or self
      rated health. Those with leg ulcers were significantly older, had more health
      problems, and were more likely to have pain-related disability. The pain
      descriptors used by patients with venous ulcers were sharp (89%), nagging (87%),
      tiring (87%), and throbbing (87%). Patients with leg ulcers reported
      significantly lower average pain (M = 6.0) than those without leg ulcers (M =
      6.6) and greater 24-hour pain relief from treatments or medications (55% vs 44%).
      Patients with venous ulcers reported greater control over their pain and greater
      coping with pain. The 2 groups did not differ significantly on depression, life
      control, or purpose in life scores. CONCLUSIONS: Compared to patients without
      venous ulcers, those patients with venous ulcers rated their pain lower and
      reported higher coping and control over pain, which may be reflected in better
      subjective pain management despite having more pain sites and disability related
      to pain. Pain management for indigent patients with and without venous ulcers
      remains a concern and needs further study.

PMID- 19752659
TI  - The relationship among pressure ulcers, oxygenation, and perfusion in
      mechanically ventilated patients in an intensive care unit.
AB  - PURPOSE: We examined the relationships among oxygenation, tissue perfusion, and
      other comorbid conditions not incorporated into the Norton Scale, and pressure
      ulcer (PU) development in subjects receiving mechanical ventilation. DESIGN:
      Descriptive, observational study. SETTING AND SUBJECTS: The setting was our
      university hospital's surgical/emergency intensive care unit in Istanbul
      province, Turkey. The sample comprised 30 patients who were older than 18 years,
      did not have a PU on admission, and had been mechanically ventilated for more
      than 24 hours when data collection began. METHODS: Skin integrity and a PU risk,
      using the Norton Scale, were administered twice daily. In addition, serum blood
      testing, vital signs, and data regarding ventilation and oxygenation status were
      obtained from the patient's electronic medical records. RESULTS: Slightly less
      than half of subjects were women (n = 14, 46.7%). Their mean age was 54.36 years
      (SD = 20.68). Pressure ulcers developed in 5 patients (16.7%); all PUs were
      located on the heel. All ulcers were initially observed as stage I lesions; 1
      progressed to a stage II ulcer and 1 progressed to a stage III ulcer. Patients
      who developed pressure ulcers have higher serum glucose levels (z = -2.198; P =
      .028), higher serum pH levels (z = -2.031; P = .028), and lower diastolic blood
      pressures (z = 0.055; P = .057) than those who remained ulcer free. CONCLUSION:
      Our results demonstrate that mechanically ventilated patients who develop PUs
      were more likely to have significantly higher blood glucose levels, significantly
      lower diastolic blood pressure values, and significantly higher serum pH values
      than were patients who remained free of PUs. Nurses who care for mechanically
      ventilated patients should recognize these factors and initiate preventive
      interventions as indicated.

PMID- 19752660
TI  - Topical treatment protocol for Stevens-Johnson syndrome and toxic epidermal
      necrolysis: a brief report.
AB  - Patients with exfoliative disorders such as Stevens-Johnson syndrome and toxic
      epidermal necrolysis may present in a variety of healthcare settings with a range
      of clinical manifestations. The amount of surface area involved varies widely and
      the full extent of involvement may not be predictable. Medical management is
      supportive and focuses initially on identifying etiology while providing
      appropriate wound care to minimize tissue loss. Patients benefit from a
      coordinated approach that often includes both burn team members and wound care
      specialists. The purpose of this article is to provide a summary of these
      conditions for the WOC nurse.

PMID- 19752661
TI  - Early postoperative complications following ostomy surgery: a review.
AB  - This article reviews early postoperative complications in adults undergoing
      ostomy surgery. Whether the ostomy is the result of an emergent or elective
      procedure, the WOC nurse and staff nurses are responsible for monitoring and
      ensuring quality healthcare for the patient. Nevertheless, many patients
      undergoing ostomy surgery experience a complication during the early
      postoperative period. Early postoperative complications not only influence
      immediate postoperative care but may also impact quality of life for the person
      living with an ostomy. Keen assessment skills, early recognition of signs and
      symptoms of a complication, and prompt interventions are crucial to maintaining a
      viable stoma and a successful surgical outcome.

PMID- 19752663
TI  - Practical strategies for treating postsurgical bowel dysfunction.
AB  - Postsurgical bowel dysfunction is a potential complication for patients
      undergoing ileoanal anastomosis, restorative proctocolectomy, and low anterior
      anastomosis. In our setting, these patients are referred to the Anorectal
      Physiology Clinic at the Townsville Hospital, Queensland, for comprehensive
      behavioral therapy. The goals of the therapy are as follows: improve stool
      consistency, improve control over stool elimination, decrease fecal frequency and
      rectal urgency, fecal continence without excessive restrictions on food and fluid
      intake, and increase quality of life. This article outlines our holistic approach
      and specific treatment strategies, including assessment, education, support and
      assistance with coping, individualized dietary and fluid modifications,
      medications, and exercise. Biofeedback is used to help patients improve anal
      sphincter and pelvic floor muscle function and bowel elimination habits.
      Information on the biofeedback component of the treatment program will be
      described in a subsequent article.

PMID- 19752664
TI  - Validity and reliability of a Turkish version of the Fecal Incontinence Quality
      of Life Scale.
AB  - PURPOSE: Anorectal disorders, including fecal incontinence, are a significant
      healthcare problem that produce bothersome symptoms and adversely affect quality
      of life. We sought to establish the validity and reliability of a Turkish
      language version of the Fecal Incontinence Quality of Life Scale (FIQOLS).
      SUBJECTS AND SETTING: Data were collected at the Fecal Incontinence-Constipation
      Biofeedback Clinic, located in the Gastroenterology Department at Ege University
      School of Medicine Hospital in Izmir, Turkey. The study sample comprised patients
      with fecal incontinence who attended the clinical assessment and agreed to
      participate in the study. INSTRUMENTS: A sociodemographic questionnaire form, the
      29-item FIQOLS, and the Fecal Incontinence Severity Index (FISI), as well as the
      36-Item Short Form Health Survey (SF-36) were administered to subjects. Both the
      FIQOLS and FISI were translated from English to Turkish by using a back
      translation technique. METHODS: Subjects initially completed the FIQOLS, FISI,
      and the SF-36 at baseline and again after a 2-week interval to allow test-retest
      reliability measurement. Internal consistency was also measured, using the
      Cronbach alpha and Spearman-Brown split-half coefficients. Test-retest
      reliability was evaluated using interclass correlation coefficient testing. The
      validity of FIQOLS with respect to the SF-36 and FISI was analyzed using Pearson
      correlation coefficients. RESULTS: Fifty subjects with fecal incontinence
      participated in the study; their mean age (SD) was 57.1 (+/-15.7) years. Almost
      two-thirds (66%) were female, and 38% did not complete primary school education.
      Test-retest reliability analysis revealed an intraclass correlation of r value
      higher than 0.70 (P < .05). The overall Cronbach alpha coefficient of instrument
      was .88; the Spearman-Brown split-half value was 0.84 for the first half of the
      tool and 0.76 for the second half. The Cronbach alpha coefficient for subfactors
      varied from .56 to .82. The FIQOLS score was found to have a statistically
      significant (P < .05) correlation with both the FISI and SF-36. CONCLUSION: These
      findings support the Turkish language version of the FIQOLS as a valid and
      reliable instrument.

PMID- 19752665
TI  - Knowledge, beliefs, attitudes, and self-reported practice concerning urinary
      incontinence in nursing home care.
AB  - BACKGROUND: Urinary incontinence (UI) is a prevalent problem in aging adults and
      is associated with significant psychosocial, physical, and economic consequences.
      In order to improve continence care, it is important to understand nurses'
      knowledge, beliefs, and attitudes about UI. This study examined the relationship
      between knowledge, beliefs, attitudes, and continence-related practice. METHODS:
      A cross-sectional design was used to gather self-reported data from 315 nurses
      and nursing assistants. INSTRUMENT: Participants completed a questionnaire
      consisting of 3 parts: (1) the Knowledge and Practice Instrument, (2) the German
      version of Henderson's Attitude and Belief Scale, and (3) demographic data.
      RESULTS: Results demonstrate that knowledge and attitude are related to practice.
      In contrast, beliefs showed no relation to either practice, or to knowledge, or
      to attitudes. The practice subscales, which can best be influenced by knowledge
      and behavioral attitude, are "assessment and information" and "drinking habit and
      excretion." CONCLUSIONS: It is worth making an effort to increase nurses'
      knowledge about UI assessment via continuing education. In addition, nurses' and
      nursing assistants' attitudes can be positively influenced by cooperation with
      advanced practice geriatric nurses.

PMID- 19752666
TI  - Clean intermittent catheterization: educational booklet directed to caregivers of
      children with neurogenic bladder dysfunction.
AB  - PURPOSE: The purpose of this study was to propose a systematic teaching and
      learning strategy for Brazilian caregivers of children with neurogenic bladder
      dysfunction(NBD), by using an illustrated booklet written in Portuguese. DESIGN:
      Descriptive study. SUBJECTS AND SETTING: Caregivers of children requiring clean
      intermittent catheterization (CIC) were approached when attending the pediatric
      urology outpatient clinic of Hospital de Base in Sao Jose do Rio Preto city,
      Brazil. METHODS: After educational sessions, a supervised procedure was done,
      with the child's caregiver observing the technique. RESULTS: Twenty-three
      caregivers of children with NBD provided feedback on a CIC teaching booklet. The
      children were all cared for at the pediatric urology outpatient clinic of a
      teaching hospital in Sao Jose do Rio Preto city, Brazil. The booklet was
      evaluated as "excellent" concerning organization and the quality of the
      illustrations by the majority of the caregivers. All caregivers stated that they
      had developed the ability to perform CIC successfully; 61% evaluated their
      learning process as "excellent," whereas 39% evaluated it as "good." CONCLUSION:
      The booklet successfully reached the goals and now is implemented in orientations
      about CIC.

PMID- 19752667
TI  - Wound: lower extremity ulcers.

PMID- 19752668
TI  - Higher skills = higher wages.

PMID- 19752669
TI  - Expanding the paradigm.

PMID- 19752670
TI  - Using the Colored Eco-Genetic Relationship Map with children.
AB  - BACKGROUND: The Colored Eco-Genetic Relationship Map (CEGRM) is a hybridized
      assessment tool that combines the ecomap, the family genogram, and the genetic
      pedigree to produce a unique, participant-generated picture of an individual's
      social networks, information exchange patterns, and sources of support. To date,
      the CEGRM has been used successfully with adults, providing insights into their
      social networks and the communication patterns they use in the update and
      exchange of health-related information. OBJECTIVE: To explore the feasibility and
      the utility of adapting elements of the CEGRM for use with children. METHODS:
      Twenty children, 7 to 10 years of age, distributed by gender, socioeconomic
      status, and geographic heritage, participated in one-on-one sessions in which
      they created modified CEGRMs using adapted art directives. A qualitative
      descriptive design and approach to analysis were used. RESULTS: Children were
      able to create a modified CEGRM, and resultant discussions provided considerable
      insights. A focused analysis revealed a kaleidoscope of social networks being
      accessed by today's children as well as surprising information exchange sources
      and patterns. Although all the children included one parent, family composition
      varied. Extended family, other adults, peers, and media sources were not only
      prevalent but also often preferred over the nuclear family as sources of health
      information. Of particular interest, mothers were rarely identified as children's
      primary source of health-related information. DISCUSSION: Elements of the CEGRM
      are adapted easily for use with children using children's drawings and may prove
      to be an effective, adjunctive assessment and interventional tool for parents,
      researchers, educators, and providers working with young children.

PMID- 19752671
TI  - Biological, psychological and behavioral, and social variables influencing
      colorectal cancer screening in African Americans.
AB  - BACKGROUND: Provider recommendation of colorectal cancer (CRC) screening is an
      important predictor of screening in African Americans. Little is known about
      influences of screening in African Americans without provider recommendations.
      OBJECTIVES: The objectives of this study were to test, using the biopsychosocial
      (BPS) model, the relative predictive strength for screening of variables grouped
      into biological, psychological and behavioral, and social system factors and to
      compare CRC screening predictors in African Americans with and without provider
      recommendations. METHODS: Secondary analysis of the 2002 Maryland Cancer Survey
      data was done using (a) hierarchical logistic regression to examine the relative
      influence of factors on screening and (b) simultaneous logistic regression to
      examine predictors of screening in individuals with and without provider
      recommendations to screen. Factors included biological (age and gender),
      psychological and behavioral (mammogram, prostate specific antigen, body mass
      index, activity level, fruit and vegetable consumption, alcohol, smoking, and
      cancer perceptions), and social system (education, employment, insurance, and
      healthcare provider access). RESULTS: The social system factor influenced CRC
      screening in the overall sample (n = 492). In African Americans with provider
      recommendations (n = 337), the very active were 2.43 (95% confidence interval
      [CI] = 1.11-5.28) times more likely to screen than were less active. Insured were
      3.25 (95% CI = 1.14-9.31) times more likely to screen than were uninsured. In
      African Americans without provider recommendations (n = 155), 65- to 69-year-olds
      were 9.99 (95% CI = 2.31-43.32) times more likely to screen than were those 50-
      to 54-year-olds without screening. DISCUSSION: The BPS model confirms social
      system factor strength in influencing CRC screening in African Americans.
      Identifying other social system variables that enhance healthcare provider access
      is critical to increase provider visits, which will generate recommendations and
      subsequent CRC screening.

PMID- 19752672
TI  - Randomized clinical trial of a school-based academic and counseling program for
      older school-age students.
AB  - BACKGROUND: Up to 17% of children in the United States have been diagnosed with
      asthma; children ages 9-14 years experience higher morbidity and mortality
      compared with other age groups. An academic and counseling program for older
      elementary students with asthma was developed in collaboration with school
      personnel, healthcare professionals, and community members: Staying Healthy
      Asthma Responsible and Prepared (SHARP). The life span development perspective
      and the Acceptance of Asthma Model were used to guide development and
      implementation. OBJECTIVES: This study aimed to establish the preliminary
      efficacy of SHARP to improve cognitive, behavioral, psychosocial, and quality-of
      life outcomes. METHODS: A two-group, longitudinal, prospective, cluster
      randomized clinical trial design was used. The sample of fourth- to sixth-grade
      students (N = 66) with asthma aged 9-12 years (M = 10.5, SD = 0.9) was 52% male,
      was racially diverse (30% Black, 36% White, and 18% biracial), and had a wide
      range of incomes. Three schools (n = 38 students) were randomized to receive
      SHARP, and two schools (n = 28 students) were assigned to usual care. Self-report
      instruments were used. RESULTS: Compared with the usual care group, statistically
      significant improvements in the SHARP group were found in student knowledge of
      asthma, reasoning about asthma, use of risk reduction behaviors, and
      participation in life activities (p < .01, effect sizes >0.7). Improvements in
      use of episode management behaviors and acceptance of asthma outcomes were
      clinically significant with medium effect sizes of 0.3-0.5. DISCUSSION: The SHARP
      Student and Community Components demonstrated preliminary efficacy for improving
      asthma knowledge, reasoning about asthma, use of episode management and risk
      reduction behaviors, acceptance of asthma in taking control and vigilance, and
      participation in life activities.

PMID- 19752673
TI  - When a parent is chronically ill: chronic fatigue syndrome.
AB  - BACKGROUND: Chronic illness may reshape not only the life of the ill parent but
      also that of the entire family, but research in this area remains limited. More
      specifically, little is known about how an ill parent and the family respond to a
      particularly devastating and controversial chronic illness, chronic fatigue
      syndrome (CFS). OBJECTIVES: The objective of this study was to describe the
      responses of the parent and the ensuing family system responses to the presence
      of chronic fatigue syndrome as a chronic parental illness. METHODS: Parents were
      interviewed individually, and then the ill parent and as many immediate family
      members as possible were interviewed collectively. After consent or assent,
      interviews were audiotaped and transcribed. Thematic analyses at the individual,
      intrafamily, and across-family levels were used to explore these phenomena.
      RESULTS: Eight ill parents first described the onset of illness, an ongoing
      struggle to receive diagnosis and care, and the significance of the illness in
      transforming present and future roles. Multiple members of the family together
      with the ill parent described how they struggled with the reality of the illness,
      the shifting roles and responsibilities, the reduced family income, and the
      frequent social isolation that could be exacerbated by the controversial nature
      of the illness. Families described and demonstrated their struggles to maintain
      normal family life and plans in the face of continuing uncertainty. DISCUSSION:
      This study is situated within current scholarship on family responses to chronic
      parental illness. The value of the family research interview is affirmed.
      Recommendations are made for future directions in family nursing research
      exploring responses of families in which a parent is chronically ill.

PMID- 19752674
TI  - Social stressors and strengths as predictors of infant birth weight in low-income
      African American women.
AB  - BACKGROUND: Perinatal racial disparities remain an elusive problem in the United
      States. African American women experience the highest rate of low-birth-weight
      deliveries. Understanding the factors contributing to infant birth weight is
      crucial to unraveling existing perinatal racial disparities. OBJECTIVE: The aim
      of this study was to broaden knowledge of predictors of infant birth weight in
      African American people by examining stress and resource factors not explored
      routinely in perinatal research along with other known correlates of birth
      weight. METHODS: A total of 119 pregnant African American women participated in
      this prospective study. Social stressors included discrimination and trauma
      exposure. Personal resources included spirituality and social support. Data on
      socioeconomic status, health behaviors, and medical conditions were collected.
      RESULTS: On average, the infants weighed 3,194 +/- 660 g at birth. Overall, 14%
      were born with birth weights less than 2,500 g. Tobacco use, number of prenatal
      visits, and discrimination due to age and physical disability were significant
      predictors of infant birth weight (R2 = .25; p >or= .001). Factors such as
      spirituality and social support were not associated with birth weight. Other
      variables traditionally associated with birth weight did not contribute to the
      model in this sample. CONCLUSION: These findings provide further evidence that
      tobacco use, number of prenatal visits, and discrimination adversely affects
      birth outcomes. By continuing to explore the social and personal experiences of
      African American women, important insights can be gained on factors that
      contribute to the pervasive racial disparities in perinatal health and contribute
      to interventions to improve the quality of healthcare for all women.

PMID- 19752675
TI  - Insight into dementia care management using social-behavioral theory and mixed
      methods.
AB  - BACKGROUND: For health organizations (private and public) to advance their care
      management programs, to use resources effectively and efficiently, and to improve
      patient outcomes, it is germane to isolate and quantify care-management
      activities and to identify overarching domains. OBJECTIVES: The aims of this
      study were to identify and report on an application of mixed methods of
      qualitative statistical techniques, based on a theoretical framework, and to
      construct variables for factor analysis and exploratory factor analytic steps for
      identifying domains of dementia care management. METHODS: Care-management
      activity data were extracted from the care plans of 181 pairs of individuals
      (with dementia and their informal caregivers) who had participated in the
      intervention arm of a randomized controlled trial of a dementia care-management
      program. Activities were organized into types, using card-sorting methods,
      influenced by published theoretical constructs on self-efficacy and general
      strain theory. These activity types were mapped in the initial data set to
      construct variables for exploratory factor analysis. Principal components
      extraction with varimax and promax rotations was used to estimate the number of
      factors. Cronbach's alpha was calculated for the items in each factor to assess
      internal consistency reliability. RESULTS: The two-phase card-sorting technique
      yielded 45 activity types out of 450 unique activities. Exploratory factor
      analysis produced four care-management domains (factors): behavior management,
      clinical strategies and caregiver support, community agency, and safety. Internal
      consistency reliability (Cronbach's alpha) of items for each factor ranged
      from.63 for the factor "safety" to.89 for the factor "behavior management"
      (Factor 1). DISCUSSION: Applying a systematic method to a large set of care
      management activities can identify a parsimonious number of higher order
      categories of variables and factors to guide the understanding of dementia care
      management processes. Further application of this methodology in outcome analyses
      and to other data sets is necessary to test its practicality.

PMID- 19752676
TI  - Symptom clusters in fibromyalgia: potential utility in patient assessment and
      treatment evaluation.
AB  - BACKGROUND: Recent evidence points to the likelihood of heterogeneity in the
      presentation and, perhaps, etiology of fibromyalgia (FM). A clearer understanding
      of the symptomatology and consideration of potential FM subtypes could add
      insights regarding this condition. OBJECTIVE: The aim of this study was to
      determine whether clusters could be identified among 20 symptoms that
      participants in a prior online study identified and to elucidate the underlying
      structure of resultant clusters. METHODS: Factor analysis was used on data from a
      study sponsored by the National Fibromyalgia Association in which 2,569 persons
      with FM responded to an online survey during a 3-day period in 2005. RESULTS: In
      this well-educated, primarily Caucasian sample, morning stiffness, fatigue, and
      not feeling rested in the morning were the symptoms with the highest severity
      scores. A series of exploratory factor analyses and subsequent confirmatory
      factor analysis with Cronbach's alpha testing led to a five-factor model with the
      following domains containing 17 symptoms: Somatic, Distress, Fibromyalgia Core,
      Dyscognition, and Sleep Problems. DISCUSSION: The findings support the
      heterogeneity of the FM experience and the presence of symptom clusters within
      the greater spectrum of symptoms comprising the FM syndrome. These observations
      suggest the possibility of tailoring interventions based upon individual patient
      symptomatology. Further work is needed to develop symptom inventories that can be
      used in clinical trials as outcome metrics and by healthcare providers to
      describe clinical burden and effect of treatments.

PMID- 19752677
TI  - Use of the concordance correlation coefficient when examining agreement in dyadic
      research.
AB  - BACKGROUND: The statistical measure used to quantify the degree of agreement or
      congruence between two research subjects has been the intraclass or the Pearson
      correlation coefficient; however, the concordance correlation coefficient (CCC)
      is another measure of agreement used to examine agreement between two observers
      or raters. OBJECTIVES: The aims of this study were to (a) highlight the
      differences among three statistical measures used to quantify the degree of
      agreement or congruence, (b) demonstrate the use of the CCC in examining
      agreement between heart failure (HF) patients and their family members, and (c)
      provide nurse researchers another method for evaluating agreement. METHODS:
      Symptom evaluation scores obtained from HF patients and their family members were
      used in the analysis of this study. To explain the use of the CCC in this
      analysis, a distinction between Pearson correlation coefficient and intraclass
      correlation coefficient is discussed. The CCC calculation is then described in
      detail. RESULTS: The HF patients in this sample were 71 +/- 9.6 years in age, 40%
      male, and 41.4% African American. Most (75%) family members were female. There
      were several different categories of family members, but most were spouses. The
      CCC results indicated that no symptom achieved good agreement, and 8 of 14
      symptoms were in moderate agreement (.4 <or= CCC <or= .7) within the dyads. Of
      the six symptoms with poor agreement (0<or= CCC < .4), HF patients and their
      family members agreed least on worsening cough (CCC = .152, 95% confidence
      interval = -.134 to .413) and bloated abdomen (CCC = .055, 95% confidence
      interval = -.224 to .325). DISCUSSION: Applying the CCC to dyadic data from HF
      patients and family members, symptoms in which the patient and family member had
      the most and least agreement were identified. The six symptoms with poor
      agreement were symptoms that can show HF decline and may be important when
      examining future nursing interventions. Further study is needed using the CCC
      with dyadic data along with other family factors that influence agreement.

PMID- 19752678
TI  - Military nursing...licensure that transcends borders.

PMID- 19752679
TI  - Nurses in the military: we salute you!

PMID- 19752680
TI  - The hospitalized nurse student: the fear of knowledge-the darkness of the
      unknown.
AB  - In this article, we aimed to share the experiences of a nurse student who
      underwent cancer treatment. We emphasized the struggle of student between the
      role as a patient and professionalism, which is required by her future career as
      a nurse.

PMID- 19752681
TI  - Outcomes of lower extremity injuries sustained during Operation Iraqi Freedom and
      Operation Enduring Freedom.
AB  - Lower extremity war injuries are complex because of changes in weaponry and
      ballistics. Outcomes of a functional lower extremity depend on early transport,
      early debridement and washout, and advanced surgical techniques such as
      microvascular procedures. The purpose of this article is to present evidence on
      the outcomes of lower extremity complex injuries and provide evidence-based
      factors that contribute to these outcomes.

PMID- 19752683
TI  - A plastic surgical nurse's military experience.
AB  - The author thanks Rachelle Springer for her great editing skills, Marcia Spear in
      showing how to upload in editorial manager, and Amanda Bailey for converting the
      pictures to JPEGs. Have you ever entertained the idea of serving in the military?
      Has your sense of patriotism ever made you feel some regret that you never served
      your country in uniform? It was this deep spirit of patriotism and my sense of
      adventure that moved me to take the oath of commitment and to give 22 years of my
      life in service to our country. This article is my personal experience of serving
      in the military as a flight nurse and a commander. It provides a brief overview
      of the aeromedical evacuation system, different job classifications, requirements
      of a flight nurse, stresses of flight, and the type of aircraft used in
      aeromedical transport.

PMID- 19752684
TI  - Care in the air: bringing the wounded closer to home.
AB  - Aeromedical evacuation (AE) is a system within the Air Force to provide patient
      care in the air during transport between levels of care. The system predominantly
      uses guard and reserve flight crew members who are arranged into rotations.
      However, when a need arises because of heavy influx of sick and wounded, the
      activation of crew members comes with short notice. This article presents my
      experiences flying AE in support of Operation Iraqi Freedom/Enduring Freedom.

PMID- 19752685
TI  - Journals from Iraq.

PMID- 19752686
TI  - Evidence-based prevention strategies for surgical site infections.

PMID- 19752687
TI  - Pay-for-Performance and Recovery Audit Contractors: the whys and wherefores of
      these programs.
AB  - Pay-for-Performance programs reward physicians, hospitals, and other providers of
      healthcare when the services they provide reach predetermined quality and
      efficiency goals. On the other hand, the Recovery Audit Contractor program is a
      form of Pay-for-Performance through which private companies hired by the Centers
      for Medicare & Medicaid Services identify improper payments made on claims of
      healthcare services to Medicare beneficiaries. Pay-for-Performance programs and
      the Recovery Audit Contractor project are discussed in this article in an effort
      to provide a baseline of understanding about these programs to those working in
      peri-operative areas.

PMID- 19752688
TI  - What's new in Shock, October 2009?

PMID- 19752689
TI  - Fms-like tyrosine kinase-3 ligand alters antigen-specific responses to infections
      after severe burn injury.
AB  - Burn patients are susceptible to opportunistic infections partly because of
      decreased immune functions, especially TH1-driven antigen-specific responses,
      which are regulated by dendritic cells. The dendritic cell growth factor, fms
      like tyrosine kinase-3 ligand (FL), has been shown to increase resistance to
      Pseudomonas aeruginosa, in a dendritic cell-dependent manner, in a mouse model of
      burn wound infection. The specific mechanisms of protection are not known. This
      study tested the hypothesis that FL can enhance production of P. aeruginosa
      specific antibodies after burn wound infection. Mice that had been previously
      exposed to P. aeruginosa were infected after burn injury by wound inoculation or
      challenged by intraperitoneal injection of heat-killed P. aeruginosa. In response
      to wound infection, FL treatments enhanced bacterial clearance and induced a
      shift from immunoglobulin (Ig) M toward IgG and IgA. However, serum levels of
      neither P. aeruginosa-specific antibodies nor interferon gamma (IFN-gamma) were
      significantly increased by FL, possibly because of decreased systemic exposure to
      bacteria. After challenge with heat-killed bacteria, which ensured equal
      exposures, FL-treated mice produced significantly greater levels of P. aeruginosa
      specific IgG2a, which correlated with an increase in serum levels of interferon
      gamma and enhanced opsonization capacity. IL-12, IL-10, and transforming growth
      factor beta were significantly increased in FL-treated mice, regardless of the
      type of challenge. These findings indicate that FL treatments after burn injury
      enhance cytokine responses to recall antigens and increase bacterial clearance.
      In addition, through its ability to promote TH1-associated antigen-specific
      responses, FL may have potential as an immunotherapy to enhance adaptive immunity
      after severe burn injury.

PMID- 19752690
TI  - In situ contact analysis of the prosthesis components of Prodisc-L in lumbar
      spine following total disc replacement.
AB  - STUDY DESIGN: A three-dimensional, nonlinear finite element analysis was
      performed to predict the in situ contact interaction of prosthesis components of
      the Prodisc-L in a multisegmental lumbar model following total disc replacement
      (TDR). OBJECTIVE: Efforts were made to investigate how the TDR implant contact
      characteristics could affect the 3-dimensional kinematics, facet loads of the
      lumbar spine following TDR. SUMMARY OF BACKGROUND DATA: Although spinal motion
      analyses of human lumbar cadaveric models after Prodisc TDR have been widely
      studied, the interaction of the disc prosthesis, particularly its in situ contact
      mechanics, is never known. METHODS: A validated intact multisegmental lumbar
      finite element model L2-L4 was altered to accommodate the TDR prosthesis through
      anterior approach. At L3-L4 disc space, the Prodisc-L of 6 degrees lordosis angle
      was implanted centrally. The model was subjected to compressive preload and pure
      moments to create flexion, extension, lateral bending, and axial rotation motion
      in physiologic range. The contact interaction between the superior component of
      Prodisc-L and the UHMWPE inlay were assessed in terms of contact region (CR),
      contact area (CA), and contact pressure (CP). Parameters of range of motion (ROM)
      and facet loading transfer were simultaneously analyzed and compared with those
      of the intact model. RESULTS: The predicted contact area was 3.5 times larger in
      flexion than that observed in extension, whereas the maximum contact pressure in
      the disc articulation was very similar with 15.1 MPa for flexion and 14.5 MPa for
      extension. Joint surface incongruence was developed in extension motion. The
      implanted model exhibited a 91.4% increase in ROM accompanied by a 150.6% rising
      in facet force during extension, while the flexion motion showed the least
      effects of TDR. In lateral bending and axial rotation, the abnormal joint "lift
      off" was not seen. CONCLUSION: The in situ function of the TDR prosthesis was
      highly dependent on how well the device could incorporate itself into the
      mechanical environment in the disc space, which has been determined by the rest
      of the spinal structures, including the retained disc anulus, articular facets,
      ligaments, vertebrae, and muscular stabilizers. The different contact interaction
      of the artificial disc components revealed here could be attributed to the
      violation of this mechanical environment which, in turn, may bring adverse
      effects to those spinal elements.

PMID- 19752691
TI  - An experimental study on initial fixation strength in transpedicular screwing
      augmented with calcium phosphate cement.
AB  - STUDY DESIGN: An experimental study. OBJECTIVE: To clarify the optimal insertion
      timing of transpedicular screws when the initial fixation strength reaches in
      maximum as calcium phosphate cement (CPC) hardens, in cases augmented by CPC to
      the vertebrae. SUMMARY OF BACKGROUND DATA: CPC goes easily into the bone
      trabeculae and excels in the bone compatibility. However, it is still unknown as
      for differences of fixation effects by CPC hardening time at actual insertion of
      the pedicle screw. METHODS: Fifty-seven vertebrae obtained from 11 human
      cadavers. The CPC and titanium pedicle screws were used. Experimental groups were
      decided as follows. (1) Control group (without CPC). (2) CPC group (augmented
      with CPC); the mixed CPC infused into the screw hole, afterwards the pedicle
      screw inserted at a set time (passage time from the initiation of powder and
      liquid agent mixing). The CPC group was further divided into 3 subgroups, with
      respect to insertion time of the pedicle screws: 2, 5, and 10 minute subgroups.
      Maximum pull-out strength was compared, and cross sectioned specimens of the 5
      and 10 minute groups were prepared and observed. RESULTS: CPC group showed a pull
      out strength of about 177% that of the control group. For inserting timing of the
      pedicle screw and pull-out strength, no apparent statistically significant
      difference was found between each subgroups, although the 10-minute group showed
      the lowest. Cross sectional observations revealed that the CPC diffused deeper
      into the bone trabeculae in the 5-minute group than in the 10 minutes.
      CONCLUSION: CPC augmentation enabled an average 77% increase of the maximum pull
      out strength compared to the control group. The study of screw insertion timing
      augmented with CPC was indicative of the fact that an increase in the initial
      fixation of the pedicle screw can be achieved when the screw is inserted before
      initiation of CPC hardening.

PMID- 19752692
TI  - Incidence and risk factors for proximal and distal junctional kyphosis following
      surgical treatment for Scheuermann kyphosis: minimum five-year follow-up.
AB  - STUDY DESIGN: Retrospective case review at a single center. OBJECTIVE: To analyze
      the incidence and risk factors associated with proximal junctional kyphosis (PJK)
      and distal junctional kyphosis (DJK) in patients undergoing instrumented spinal
      fusion for Scheuermann kyphosis. SUMMARY OF BACKGROUND DATA: Previously reported
      risk factors for junctional kyphosis include improper end vertebrae selection,
      curve correction greater than 50%, or excessive junctional soft tissue
      dissection. METHODS: Clinical and radiographic data on 67 patients (mean age 37)
      from a single center treated with instrumented fusion for Scheuermann kyphosis
      were reviewed. All patients had complete radiographic data with a minimum 5-year
      follow-up (mean: 73 months). Abnormal PJK was defined by a proximal junctional
      angle greater than 10 degrees and at least 10 degrees greater than the
      corresponding preoperative measurement. DJK was similarly defined between the
      caudal endplate of the lower instrumented vertebra to the caudal endplate that
      was 1 vertebra below. RESULTS: The incidence of PJK as defined above was seen in
      20 patients (30%). The development of PJK was associated with failure to
      incorporate the proximal end vertebra (15 patients), disruption of junctional
      ligamentum flavum (3 patients), or combination of both (2 patients). The most
      common cause of inappropriate end vertebra selection was poor visualization of
      the upper thoracic vertebra.DJK occurred in 8 patients (12%) and 7 of them had
      fusion short of including the first lordotic disc. CONCLUSION: The incidence of
      PJK can be minimized by the appropriate selection of the upper end vertebra to be
      fused and avoiding disruption of the junctional ligamentum flavum. The
      development of DJK can be minimized by incorporation of the first lordotic disc
      into the fusion construct.

PMID- 19752693
TI  - Metastasis of breast cancer to a lumbar spinal nerve root ganglion.
AB  - STUDY DESIGN: A case report of a surgically treated metastasis of breast cancer
      to the L2 nerve root ganglion. OBJECTIVES: To report of an uncommon site of
      metastasis as the first manifestation of distant hematogenous spread of breast
      cancer mimicking a benign lesion. SUMMARY OF BACKGROUND DATA: Although metastatic
      disease is a common condition there are limited reports of metastases to the
      spinal nerve root ganglion. To our knowledge this is the fourth reported case and
      the first report of a metastasis of a breast carcinoma. METHODS: A 46-year-old
      female patient was admitted with severe right sided radicular pain and moderate
      weakness of hip flexion and knee extension. Magnetic resonance imaging revealed a
      small lesion of the L2 nerve root. Intraoperatively an intradural tumor was
      encountered and debulked. The procedure was followed by radiation therapy.
      RESULTS: The operative procedure resulted in complete pain resolution with
      improved motor function. The histologic examination confirmed the tumor to be a
      metastasis of breast cancer as determined by immunohistological staining. The
      patient remained recurrence free at 6 month follow-up. CONCLUSION: Although very
      rare, metastasis to the spinal nerve root ganglion can be the first manifestation
      of distant hematogenous metastases of breast cancer. The clinical course is
      characterized by increasing radicular symptoms-especially intractable pain. The
      radiologic appearance might mimic a benign lesion. Surgical intervention with
      tumor debulking followed by radiotherapy provides local tumor control and
      palliation from pain.

PMID- 19752694
TI  - Agenesis of the right internal carotid artery and Klippel-Feil syndrome: case
      report.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To describe the case of a Klippel-Feil
      anomaly associated with carotid agenesis. SUMMARY OF BACKGROUND DATA: Klippel
      Feil anomaly is a spinal malformation characterized by fusion of the cervical
      vertebrae. Four subtypes have been identified for this congenital disorder with
      different severity of vertebral fusion and different extra-axial anomalies. Most
      cases are sporadic, although autosomal dominant and autosomal recessive cases are
      recognized. It can cause neurologic disorders and is associated to vascular
      abnormalities. However, agenesis of internal carotid and Klippel-Feil syndrome is
      an unusual association. METHODS: A 49-year-old woman came to our attention for
      recurrent transitory ischemic attacks presenting with weakness of left limbs
      associated with sensory abnormalities. Neurologic examination revealed mild left
      limb weakness and tactile hypoesthesia. RESULTS: Brain magnetic resonance (MR)
      and MR angiography demonstrated absence of the right internal carotid and the
      middle right cerebral artery was filled from the basilar artery. Fusion of
      vertebral bodies was documented at MR and confirmed at spinal CT scan. The day
      after the admission the neurologic examination became normal. Ticlopidine was
      then started. CONCLUSION: Literature of vascular abnormalities in association
      with Klippel-Feil syndrome takes the form of anecdotal reports. Aortic
      coarctation, vertebral artery dissection, aneurysms, persistent trigeminal
      artery, and abnormal origin of internal carotid are described. An unusual
      association of carotid internal agenesis and Klippel-Feil syndrome is reported
      with a literature review.

PMID- 19752695
TI  - Unstable subaxial cervical spine injury with normal computed tomography and
      magnetic resonance initial imaging studies: a report of four cases and review of
      the literature.
AB  - STUDY DESIGN: Case series. OBJECTIVE: To describe 4 cases of unstable subaxial
      cervical spine injury not demonstrated with initial radiograph, computed
      tomography (CT), and magnetic resonance (MR) imaging. SUMMARY OF BACKGROUND DATA:
      When evaluating the cervical spine for ligamentous or osseous injuries in the
      blunt trauma patient population, negative predictive value measurements of 100%
      for CT and MR imaging have been published. Unstable subaxial cervical spine
      injury has rarely been reported in the spine literature in conjunction with
      initial radiograph, CT, and MR imaging demonstrating no osseous or ligamentous
      injury. Historically, reports of subacute cervical spine instability following
      trauma exist and were presented before the availability of MR and multidetector
      CT imaging. METHODS AND RESULTS: We report 4 examples of unstable subaxial
      cervical spine injury each with initial imaging interpreted as negative. All 4
      cases presented at a level-one tertiary care facility. Follow-up radiographs
      demonstrated unstable cervical spine injuries requiring surgical stabilization.
      CONCLUSION: Notwithstanding high sensitivities, specificities, and negative
      predictive values for cervical spine imaging and "clearance" mechanisms, 4 cases
      that illustrate the potential for undetected unstable cervical spine injuries are
      presented. Tremendous advancements in medical imaging have been made. However,
      radiograph, CT, and MR imaging may still fail to accurately translate the
      anatomic and dynamic complexity of the cervical spine into digital images that
      accurately guide clinical practice. A full understanding of and keen appreciation
      for the fact that no imaging technique, classification method, or clearance
      protocol can produce 100% sensitivity at all times is essential. These case
      reports cumulatively demonstrate a 0.04% to 0.2% incidence of undetected cervical
      injury requiring surgical stabilization. Removing cervical collar immobilization
      as quickly as possible based on negative interpretation of imaging data may prove
      harmful in a measurable percentage of patients and must be undertaken with
      caution only after clinical correlation and strict follow-up is established.

PMID- 19752697
TI  - Thirty-fourth Harrington Guest Lecture, SRS, 2008. Harrington's contributions in
      perspective.

PMID- 19752698
TI  - Transforaminal lumbar interbody fusion versus anterior lumbar interbody fusion as
      an adjunct to posterior instrumented correction of degenerative lumbar scoliosis:
      three year clinical and radiographic outcomes.
AB  - STUDY DESIGN: Prospective, nonrandomized consecutive single surgeon series.
      OBJECTIVE: To compare the clinical and radiographic outcomes in degenerative
      lumbar scoliosis (DLS) patients treated with posterior instrumented correction
      and fusion with additional anterior lumbar interbody fusion (ALIF) versus
      transforaminal lumbar interbody fusion (TLIF) to help define whether anterior
      surgery should be routinely required in treating DLS. SUMMARY OF BACKGROUND DATA:
      The benefits of interbody support in promoting postoperative stability and
      arthrodesis are well established. Whether the interbody fusion is better
      performed from an anterior or posterior approach has not been studied for
      patients undergoing surgical correction for DLS. METHODS: Forty consecutive
      patients with DLS, stenosis, and olisthesis underwent posterior instrumented
      reduction/arthrodesis at average 7 levels (range: 4-9 levels). Additional ALIF
      was performed in 20 patients, TLIF in the other 20. Follow-up averaged 38 months
      (24-68 months). Oswestry Disability Index (ODI), visual analog pain scores (VAS)
      were evaluated preoperative, 1 and 2 years postoperative. Radiograph measurements
      included the scoliosis, T12 to S1 lordosis, coronal and sagittal balance, and
      pelvic incidence. CT evaluation of the fusion integrity was performed after 1
      year. RESULTS: The ALIF group complications included 4 nonunions, 5 adjacent
      level fractures, 5 adjacent degeneration, 3 infections, and 1 footdrop. Revision
      surgery was performed in 8 of 20. Medical complications included 2 nonfatal
      pulmonary embolus, 1 ileus requiring colostomy, and 1 stroke. TLIF group
      complications included 3 adjacent segment degeneration, 2 adjacent fractures, 2
      nonunions, and 1 infection and transient footdrop. Two of 20 required revision
      surgery. VAS and ODI improvements for both groups showed significant improvement
      from preoperative (P < 0.0019) but were not different. Deformity correction was
      also similar (70%) between ALIF and TLIF groups. CONCLUSION: With current
      deformity correction techniques, both ALIF and TLIF are effective in DLS surgery.
      Anterior surgery is not routinely required to treat all cases of DLS.

PMID- 19752699
TI  - En bloc spondylectomy for the treatment of spinal tuberculosis with fixed and
      sharply angulated kyphotic deformity.
AB  - STUDY DESIGN: Thirty-four patients having advanced spinal tuberculosis with
      angulated kyphotic deformity who underwent posterior en bloc spondylectomy were
      reviewed. OBJECTIVE: To evaluate clinical outcomes of posterior en bloc
      spondylectomy in patients having spinal tuberculosis with angulated kyphotic
      deformity. SUMMARY OF BACKGROUND DATA: Spinal tuberculosis may be associated with
      angulated kyphotic deformity. The conventional treatment for angular kyphosis is
      combined anterior and posterior decompression, fusion, and stabilization.
      METHODS: From 1998 to 2005, 34 patients (mean age, 25.1 years) underwent
      posterior 1-stage en bloc spondylectomy. The level of tuberculosis and kyphosis
      was T9 in 2 patients, T10 in 5, T11 in 13, T12 in 14, and L1 in 12. The anterior
      column with tuberculosis present was completely removed by en bloc spondylectomy.
      Strut autograft was used to restore anterior column stability. Posterior pedicle
      screw fixation and fusion were typically performed. RESULTS.: No perioperative
      mortality occurred in these patients. At follow-up, according to Odom's
      classification, the excellent outcome was seen in 9 patients, good in 23, fair in
      1, and poor in 1. The kyphotic Cobb angle improved from the preoperative average
      of 57.8 degrees to a postoperative average of 11.4 degrees. The average
      horizontal distance between C7 and S1 was 13.9 mm before surgery and 3.9 mm after
      surgery. Seventeen patients showed a postoperative improvement in American Spinal
      Injury Association grade after the operation. The perioperation complication
      occurred in 3 of the 34 cases. Two patients had evidence of screw loosening at
      follow-up. Ten patients had questionable fusion or pseudarthrosis. CONCLUSION:
      The purpose of this article is more to describe the technique of posterior en
      bloc spondylectomy in patients with spine tuberculosis with kyphotic deformity.
      From the results of this preliminary study, en bloc spondylectomy for the
      treatment of spinal tuberculosis with angulated kyphotic deformity can be a safe
      and effective technique.

PMID- 19752700
TI  - Correlation of scoliosis curve correction with the number and type of fixation
      anchors.
AB  - STUDY DESIGN: Clinical and radiologic assessment derived from a prospective
      multicenter data base of adolescent idiopathic scoliosis (AIS) patients.
      OBJECTIVE: We investigated if "implant density" or the number of screws
      correlated with the major curve (thoracic or lumbar) correction at 2 years in
      patients with AIS. We also investigated the effect of implant density on the
      change in sagittal contour before surgery to after surgery. SUMMARY OF BACKGROUND
      DATA: Controversy exists regarding number and type of spinal anchors and the
      number of implant sites used that result in improved correction in AIS. METHODS:
      A prospective database of patients with AIS treated by posterior instrumentation
      between 1995 and 2004 was analyzed. The major curve correction expressed as %
      correction (from preoperative to 2 years postoperative) was correlated with the
      percentage of implants relative to the number of available implant sites within
      the measured Cobb angle. Correlation of % correction to the number of hooks,
      wires, and screws was also performed. We also analyzed the change in sagittal
      contour T2-T12, T5-T12, and T10-L2 before surgery and after surgery. This
      absolute change was then correlated with implant density, as was the number of
      hooks, wires, and screws. RESULTS: There were 292 patients included with all 6
      Lenke curve types represented (250 with major thoracic curves and 42 with major
      lumbar curves). The overall % coronal Cobb correction was 64% (range: 11%-98%).
      The implant density within the major curve averaged 61% (range: 6%-100%). There
      was a significant correlation between implant density and % curve correction (r =
      0.31, P < 0.001). The number of each implant type (hooks, wires, and screws) in
      the construct did not correlate with the % correction; however, the average %
      correction of the major curve was greater when the Cobb levels were instrumented
      only with screws (64%) compared to hooks alone (55%), P < 0.01. The greatest %
      correction 78% was achieved when bilateral segmental screws were used (100% screw
      density). The higher the implant density within the major thoracic curve, the
      greater the postoperative loss of kyphosis at T2-T12 (r = -0.13, P < 0.01) and T5
      T12 (r = -0.16, P < 0.001). At T10-L2, increasing screw implant density
      correlated with decreasing kyphosis (r = -0.40, P < 0.001), whereas increasing
      hook implant density correlated with increasing kyphosis (r = 0.33, P < 0.001).
      CONCLUSION: Major curve correction at 2 years correlates most with the implant
      density that is correction increases with the number of implants used within the
      measured Cobb levels. Although the absolute number of screws used did not
      correlate with correction, there was an advantage in lumbar and thoracic curves
      to using screws compared to hooks. Sagittal contour in the thoracic spine became
      less kyphotic than the higher the implant density.

PMID- 19752701
TI  - Treatment of spinal deformities in patients with diastrophic dysplasia: a long
      term, population based, retrospective outcome study.
AB  - STUDY DESIGN: A long-term, population based, retrospective follow-up study.
      OBJECTIVE: To evaluate long-term outcomes of brace and surgical treatment for
      spinal deformities in patients with diastrophic dysplasia (DD). SUMMARY OF
      BACKGROUND DATA: Literature on the brace treatment and surgery of spinal
      deformities in patients with DD is limited. METHODS: All patients with DD
      undergoing either brace treatment or surgery for spinal deformity with a minimum
      of 2 years follow-up were identified in our country. Eight patients had undergone
      brace treatment and 12 had been treated operatively. Two patients had early
      progressive and the rest idiopathic-like scoliosis. Five patients underwent
      posterior only, 1 anterior only, and 6 anteroposterior surgery. Patients' mean
      age at the beginning of brace treatment was 6.9 (range, 0.9-12.7) years and at
      the time of surgery 13.4 (range, 6.5-20.1) years. The follow-up time averaged 17
      (range, 6.6-44.3) years for the brace and 14.0 (range, 2.1-37.2) years for the
      surgical treatment group. The radiographic follow-up rate was 100%. RESULTS: Both
      thoracic and lumbar curves progressed during brace treatment (mean major curve
      progression 12%, range, -43%-53%). Before surgery, the mean Cobb angle of the
      thoracic curve was 68 degrees (range, 42 degrees-100 degrees) and 46 degrees (25
      degrees-68 degrees) in the lumbar spine. At final follow-up visit, the mean
      correction was 23% (-6%-76%) for the thoracic curve and 25% (-68%-82%) for the
      lumbar curve. The correction of the major curve was higher in patients undergoing
      anteroposterior versus posterior only (40% vs. 13%, P = 0.017). Five (42%)
      operated patients had significant complications. The SRS-24 yielded 92 (79-103)
      points for the brace treatment and 93 (73-114) points for the surgical group,
      respectively. CONCLUSION: Brace treatment does not prevent progression of the
      spinal deformity in patients with DD. Anteroposterior surgery is indicated in
      patients with severe spinal deformities. The risk for major complications is high
      especially in patients with marked kyphosis.

PMID- 19752702
TI  - Thoracic pedicle screw instrumentation: the learning curve and evolution in
      technique in the treatment of adolescent idiopathic scoliosis.
AB  - STUDY DESIGN: Retrospective review. OBJECTIVE: The purpose of this study is to
      evaluate the learning curve and associated evolution in surgical technique with
      thoracic pedicle screw instrumentation in adolescent idiopathic scoliosis (AIS).
      SUMMARY OF BACKGROUND DATA: Common treatment for AIS now includes posterior
      spinal fusion, using thoracic pedicle screws (TPS). It is critical to assess the
      efficacy, safety profile, and learning curve associated with this technique as
      its use becomes more widespread among inexperienced surgeons. METHODS:
      Retrospective review of the senior author's first 96 TPS cases for Lenke Type I
      AIS curves. Multiple regression techniques were used to discern whether
      increasing case number (CN) was associated with improved perioperative and 2-year
      minimum radiographic and clinical outcomes. The 96 cases were divided into 4
      equal quartiles of 24 cases/group (i.e., Q1-Q4) and compared using analysis of
      variance measures. RESULTS: A total of 1169 thoracic pedicle screws were placed
      in 96 patients. We found a significant correlation between CN and major curve
      correction at 2 years (P < 0.0001), inverse correlation between CN and length of
      stay (P = 0.02), and estimated blood loss (P = 0.03), but no differences in cell
      saver or complications. Univariate analysis revealed significant inverse
      correlations between increasing CN and transfusion rate (P = 0.02) and operative
      times (P = 0.0001). Total number of screws placed (Q1:9.4 vs. Q4:16.2, P <
      0.0001) and number of screws/level (Q1:0.98 vs. Q4:1.64, P < 0.0001) increased
      linearly with increasing CN, whereas the average time for screw placement
      (Q1:24.2 vs. Q4:11.4 minutes, P < 0.0001) and ability to maintain T2-T12 kyphosis
      decreased (Q1:0.21 vs. Q4:-5.5 P = 0.02) with increasing CN. CONCLUSION: There is
      a significant learning curve associated with thoracic pedicle screw placement in
      AIS. We describe several technical steps that can be taken to increase the safety
      of screw placement at the beginning of the learning curve. Inexperienced surgeons
      should expect a gradual improvement over time in radiographic and clinical
      outcomes.

PMID- 19752703
TI  - Does treatment (nonoperative and operative) improve the two-year quality of life
      in patients with adult symptomatic lumbar scoliosis: a prospective multicenter
      evidence-based medicine study.
AB  - STUDY DESIGN: Prospective observational cohort study with matched and unmatched
      comparisons. Level II evidence. OBJECTIVE: The purpose of this study is to
      compare results of adult symptomatic lumbar scoliosis (ASLS) patients treated
      nonoperatively and operatively. This is an evidence-based prospective multicenter
      study to answer the question of whether nonoperative and operative treatment
      improves the quality of life (QOL) in these patients at 2-year follow-up. SUMMARY
      OF BACKGROUND DATA: Only 1 paper in the peer-reviewed published data directly
      addresses this question. That paper suggested that operative treatment was more
      beneficial than nonoperative care, but the limitations relate to historical
      context (all patients treated with Harrington implants) and the absence of
      validated patient-reported QOL (QOL) data. METHODS: This study assesses 160
      consecutively enrolled patients (ages 40-80 years) with baseline and 2-year
      follow-up data from 5 centers. Lumbar scoliosis without prior surgical treatment
      was defined as a minimum Cobb angle of 30 degrees (mean: 54 degrees for patients
      in this study). All patients had either an Oswestry Disability Index (ODI) score
      of 20 or more (mean: 33) or Scoliosis Research Society (SRS) domain scores of 4
      or less in pain, function, and self-image (mean: 3.2) at baseline. Pretreatment
      and 2-year follow-up data collected prospectively included basic radiographic
      parameters, complications and SRS QOL, ODI, and Numerical Rating Scale back and
      leg pain scores. RESULTS: At 2 years, follow-up on the operative patients was 95%
      and for the nonoperative patients it was 45%. The demographics for the
      nonoperative patients who were followed up for 2 years versus those who were lost
      to follow-up were identical. The operative cohort significantly improved in all
      QOL measures. The nonoperative cohort did not improve and nonsignificant decline
      in QOL scores was common. At minimum 2-year follow-up, operative patients
      outperformed nonoperative patients by all measures. CONCLUSION: It would appear
      from this study that common nonoperative treatments do not change the QOL in
      patients with ASLS at 2-year follow-up. However, operative treatment does
      significantly improve the QOL for this group of patients. Our conclusions are
      limited by the fact that we were only able to follow-up 45% of the nonoperative
      group to 2-year follow-up, in spite of extensive efforts on our part to
      accomplish such.

PMID- 19752704
TI  - Pain and disability determine treatment modality for older patients with adult
      scoliosis, while deformity guides treatment for younger patients.
AB  - STUDY DESIGN: Multi-center, retrospective review. OBJECTIVE: Identify age
      associated clinical and radiographic features correlating with AS treatment.
      SUMMARY OF BACKGROUND DATA: Little information exists about factors determining
      treatment for adult scoliosis (AS). Existing studies have not evaluated age
      stratified differences. METHODS: Multicenter, retrospective review of 290
      patients treated for AS. Patients divided into operative (OP) or nonoperative
      (NON), and age stratified into 3 groups (G1 = <50 years, G2 = 50-65 years, G3 =
      >65 years). Demographic and spinopelvic radiographic parameters evaluated. Health
      related quality of life (HRQL) measures included SRS-22, Oswestry Disability
      Index (ODI), visual analog pain scale. RESULTS: Treatment groups (OP, n = 137;
      NON, n = 153) demonstrated similar age (OP = 52.7 years; NON = 55.5 years; P >
      0.05) and comorbidities. OP had larger thoracic curves than NON (OP = 51 degrees,
      NON = 45 degrees; P < 0.05). OP had worse HRQL scores than NON (SRS = 2.95 vs.
      3.12, P < 0.05; ODI = 33.4 vs. 28.7, P < 0.05; visual analog pain scale = 6.9 vs.
      5.6, P < 0.05, respectively). Age stratification of OP demonstrated larger curves
      in G1 and G2 versus G3, progressively worsening sagittal imbalance in older age
      groups, and worse HRQL scores in G3 versus G1 and G2. Age stratification of NON
      demonstrated worsening sagittal imbalance with age, however, other radiographic
      values and HRQL scores were similar between all NON age groups. Treatment
      stratification of age groups demonstrated G1-OP had greater deformity than G1-NON
      (mean thoracic curve: G1-OP = 53 degrees, G1-NON = 43 degrees; P < 0.05) but
      similar HRQL values. Whereas G2 and G3-OP had similar radiographic coronal and
      sagittal values as G2 and G3-NON, but worse HRQL scores. CONCLUSION: Counter to
      previous reports, age, comorbidities, and sagittal balance did not influence
      treatment modality for AS. Operative treatment for younger patients was driven by
      increased coronal plane deformity. Conversely, pain and disability mandated
      treatment for older patients, independent of radiographic measures. These
      findings suggest that AS patients do not become uniformly disabled with age, and
      that disability can not be solely predicted by radiographic findings. These data
      should be considered when considering treatment for AS.

PMID- 19752705
TI  - Revision surgery after primary spine fusion for idiopathic scoliosis.
AB  - STUDY DESIGN: Retrospective case series. OBJECTIVE: The objective of this study
      was to review the overall prevalence of, and indications for, reoperations after
      the index spine fusion for idiopathic scoliosis at our center. SUMMARY OF
      BACKGROUND DATA: Spine fusions for idiopathic scoliosis are expected to be the
      final therapeutic intervention in management. In a recent publication in 2006,
      reoperations after index spine fusion for idiopathic scoliosis were reported in
      12.9% of patients at a single institution (n = 1046). METHODS: A spinal deformity
      database search at our center identified all primary anterior, posterior, and
      circumferential spinal fusions performed for idiopathic scoliosis (1985-2003). A
      total of 1057 patients were identified whose mean age was 14.4 years (7-22 years)
      with minimum 2 year follow-up after index surgery. Study cohort consisted
      patients who underwent reoperation for any reason after index fusion procedure.
      RESULTS: Of the 1057 spinal fusions for idiopathic scoliosis, 41 (3.9%) underwent
      reoperation. Primary surgeries were: 11 anterior spinal fusions, 25 posterior
      spinal fusions, and 5 circumferential spinal fusions. Mean follow-up was 5.7
      years (2-10.8). Forty-seven additional procedures were performed during 46
      reoperations at an average of 26 months after index procedure (1 week-73 months).
      Of the 47 reoperations, 20 (43%) were revision spinal fusions (for
      pseudarthroses, uninstrumented curve progression or junctional kyphosis), 16
      (34%) because of infections (5 acute, 11 chronic), 7 (15%) for implant removals
      due to pain and/or prominence (4 complete, 3 partial), 2 (4%) were revision of
      loosened implants, and 2 (4%) were elective thoracoplasties. CONCLUSION: This
      study documented a 3.9% overall reoperation rate at our medical center, a 3-fold
      lower reoperation rate than the previously reported 12.9%. The most common
      reoperations were for infections (34%), pseudarthroses (26%), and postoperative
      curve progression of the adjacent unfused spine (17%).

PMID- 19752706
TI  - Low back pain in patients treated surgically for scoliosis: longer than sixteen
      year follow-up.
AB  - STUDY DESIGN: A retrospective study. OBJECTIVE: To evaluate long-term outcome
      regarding low back pain (LBP) in patients treated surgically for scoliosis.
      SUMMARY OF BACKGROUND DATA: Measures of long-term outcome after surgery for
      scoliosis have focused mainly on radiologic changes. However, subjective symptoms
      such as LBP after surgical treatment are of great concern to patients who undergo
      surgical treatment for scoliosis. METHODS: Thirty-two patients treated surgically
      for scoliosis between 1976 and 1989 were included in this study. The mean
      duration of follow-up was 21.1 years. Eighteen patients had adolescent idiopathic
      scoliosis, 8 had congenital scoliosis, and 6 had symptomatic scoliosis. We
      evaluated long-term outcome by direct interview. Degree of LBP was evaluated by
      visual analogue scale score and Moskowitz classification in addition to clinical
      and radiologic evaluation. Patients were also asked to complete the SF-36
      questionnaire. RESULTS: Mean visual analogue scale score at the latest follow-up
      was 21 (0-80), and 15% of patients had occasional or frequent LBP in Moskowitz
      classification. On the SF-36, score for bodily pain was not markedly different
      from that for age-matched controls. Among radiologic findings, level of distal
      fusion had no effect on the incidence or severity of LBP. Furthermore,
      preoperative Cobb angle, latest Cobb angle, and degenerative changes of subjacent
      segment each exhibited no correlation with degree of LBP, either. On the other
      hand, sagittal balance was a factor affecting LBP following scoliosis surgery.
      CONCLUSION: We evaluated long-term outcomes regarding LBP following scoliosis
      surgery. Regardless of residual back deformity, LBP was found to be no more
      frequent than in the normal population in Japan. Positive sagittal balance at the
      latest follow-up was a factor significantly contributing to LBP following
      scoliosis surgery.

PMID- 19752707
TI  - Long adult spinal deformity fusion to the sacrum using rhBMP-2 versus autogenous
      iliac crest bone graft.
AB  - STUDY DESIGN: Comparative study. OBJECTIVE: To compare the radiographic outcome
      of patients undergoing long spinal deformity surgery to the sacrum/ilium, using
      either rhBMP-2 without iliac crest bone graft (ICBG) or ICBG without rhBMP-2.
      SUMMARY OF BACKGROUND DATA: rhBMP-2 has been shown to be more effective in
      promoting successful bone union in patients undergoing single level lumbar spinal
      fusion than ICBG. However, to the best of our knowledge, there are no studies
      that compare the efficacy of rhBMP-2 versus ICBG in long spinal deformity
      surgery. METHODS: To obtain uniform background, we selected patients with adult
      spinal deformity who underwent primary spinal fusion from the thoracic spine to
      the sacrum/ilium and had a minimum 2-year follow-up. Fifty-five consecutive
      patients, consisting of 32 patients who underwent a fusion using ICBG without
      rhBMP-2 (ICBG group) and 23 patients who underwent a fusion using rhBMP-2 without
      ICBG (BMP group) were analyzed. RESULTS: The 2 groups were similar with respect
      to age, gender, smoking history, comorbidity, and body mass index. The average
      number of vertebrae fused (11.3 in both groups) and the degree of preoperative
      deformity (major Cobb angle 58.3 degrees in ICBG group vs. 54.2 degrees in BMP
      group) were also similar in both groups. All but 2 patients had both anterior and
      posterior surgery. Both groups were similar in terms of final deformity
      correction. The average total amount of rhBMP-2 used in the BMP group was 119.2
      mg (anterior 11.6 mg/level; posterior 10.0 mg/level). Of the 32 patients in the
      ICBG group, 9 patients (28.1%) developed a pseudarthrosis, while only 1 of 23
      patients (4.3%) in the BMP group developed a pseudarthrosis with the caveat that
      the follow-up period was shorter in the BMP group (average follow-up of 4.9 vs.
      2.7 years). CONCLUSION: The pseudarthrosis rate in the BMP group compares
      favorably to pseudarthrosis rate in ICBG group, suggesting that the use of rhBMP
      2 without iliac harvesting leads to a competitive fusion rate in long adult
      spinal deformity surgery, while avoiding ICBG harvest site morbidity.

PMID- 19752708
TI  - Posterior vertebral column resection for severe pediatric deformity: minimum two
      year follow-up of thirty-five consecutive patients.
AB  - STUDY DESIGN: Retrospective review of a prospectively accrued patient cohort.
      OBJECTIVE: The ability to treat severe pediatric spinal deformity through an all
      posterior vertebral column resection (VCR) has obviated the need for a
      circumferential approach in both primary and revision settings. We examined
      indications, correction rates, and complications of this challenging procedure in
      the pediatric population. SUMMARY OF BACKGROUND DATA: Traditionally, severe
      pediatric spinal deformities were treated through a combined anterior/posterior
      spinal fusion. METHODS: Between 2000 and 2005, 35 consecutive patients underwent
      a posterior-only VCR by 1 of 2 surgeons at a single institution. Patients were
      divided into 5 diagnostic categories: (1) severe scoliosis (S) (n = 2; mean, 115
      degrees; range, 79-150 degrees; average flexibility, 12%); (2) global kyphosis
      (GK) (n = 3; mean, 101 degrees; range, 91-113 degrees; average flexibility, 16%);
      (3) angular kyphosis (AK) (n = 10; mean, 86 degrees; range, 45-135 degrees,
      average flexibility, 23%); (4) kyphoscoliosis (KS) (n = 8; mean kyphosis, 103
      degrees/scoliosis 87 degrees; mean combined, 190 degrees; range, 144-237
      degrees); (5) congenital scoliosis (CS) (n = 12; mean, 43 degrees; range, 23-69
      degrees; average flexibility, 20%). There were 20 primary/15 revision surgeries.
      There were 20 one-level, 11 two-level, and 4 three-level resections. RESULTS: The
      major curve correction averaged: Group S = 61 degrees/51%, Group GK = 56
      degrees/55%, Group AK = 51 degrees/58%, Group KS = 98 degrees/54%, and Group CS =
      24 degrees/60%. The average OR time was 460 minutes (range, 210-822), with an
      average EBL of 691 mL (range, 125-2200). There were no spinal cord-related
      complications; however, 2 patients (8.5%) lost intraoperative neuromonitoring
      data during correction with data returning to baseline following prompt surgical
      intervention. Two patients had implant revisions, 1 for a delayed deep infection
      at 2 years and the other for implant prominence at 3-year follow-up. CONCLUSION:
      A posterior-based VCR is a safe but challenging technique to treat severe primary
      or revision pediatric spinal deformities. Intraoperative SCM (especially motor
      evoked potentials) is mandatory to prevent spinal cord-related neurologic
      complications. Dramatic radiographic and clinical correction of these deformities
      can be obtained via a posterior-only approach.

PMID- 19752709
TI  - Is spine deformity surgery in patients with spastic cerebral palsy truly
      beneficial?: a patient/parent evaluation.
AB  - STUDY DESIGN: Retrospective clinical outcome study. OBJECTIVE: To evaluate the
      clinical outcomes and satisfaction associated with the surgical treatment of
      neuromuscular spinal deformity secondary to cerebral palsy. SUMMARY OF BACKGROUND
      DATA: Controversy still exists regarding whether spinal deformity surgery is
      truly a beneficial surgery for patients with cerebral palsy (CP) since there is
      limited functional benefit and higher perioperative complications rates in this
      patient population. METHODS: Neuromuscular patient evaluation questionnaires were
      answered retrospectively by 84 patients/families of spastic CP patients
      undergoing spinal fusion. The average follow-up was 6.2 years (range: 2-16). The
      questionnaires were designed to assess expectation, cosmesis, function, patient
      care, quality of life, pulmonary function, pain, health status, self-image, and
      satisfaction. Questionnaire results, complications, and radiographic data were
      divided into "satisfied group" and "less satisfied group" and we analyzed reasons
      of satisfaction and dissatisfaction. RESULTS: The overall satisfaction rate was
      92%. Ninety-three percent reported improvement with sitting balance, 94% with
      cosmesis, and 71% in patient's quality of life. Functional improvements seemed
      limited, but 8% to 40% of the patients still perceived the surgical results as
      improvement. The postoperative complication rate was 27%. The mean preoperative
      Cobb angle of the major curve was 88 degrees (range: 53 degrees-141 degrees),
      which corrected to 39 degrees (range: 5 degrees-88 degrees) after surgery. The
      less satisfied group had a significantly higher late complication rate, less
      correction of the major curve, greater residual major curve, and hyperlordosis of
      the lumbar spine after surgery. CONCLUSION: Despite the perioperative
      difficulties seen with CP patients, the majority of the patient/parents were
      satisfied with the results of the spinal deformity surgery. Functional
      improvements were limited but 8% to 40% of the patients still perceived the
      results as improved. The reason for less than optimal satisfaction appears to be
      due to less correction of the major curve, greater residual major Cobb angle,
      hyperlordosis of the lumbar spine after surgery, and late postoperative
      complications.

PMID- 19752710
TI  - Long-term clinical outcomes following en bloc resections for sacral chordomas and
      chondrosarcomas: a series of twenty consecutive patients.
AB  - STUDY DESIGN: Retrospective study of 20 consecutive patients who underwent en
      bloc tumor excision of sacral chordomas and chondrosarcomas. OBJECTIVE: To
      evaluate the functional and oncological outcomes following en bloc tumor excision
      for sacral chordomas and chondrosarcomas. SUMMARY OF BACKGROUND DATA: Chordomas
      and chondrosarcomas are 2 of the most common malignant primary tumors of the
      sacrum in adults. To date, few large clinical series with en bloc resection of
      these tumors exist. METHODS: An institutional primary spine tumor surgical
      database was retrospective reviewed. Twenty consecutive patients with sacral
      chordomas and chondrosarcomas who underwent primary en bloc tumor excisions from
      2002 to 2007 were included in the study. Surgical margin, perioperative
      complications, and postoperative functional status in these patients were
      analyzed. Disease-free survival following en bloc tumor excision was determined
      using the Kaplan-Meier method. RESULTS: The study cohort included 8 males and 12
      females with an average age of 53.5 years and a man follow-up of 47.8 months.
      Wide or marginal en bloc resection was achieved in 14 patients. In 6 other
      patients, tumor was identified at the surgical margins, and they were considered
      to have contaminated/intralesional resections. The 30-day perioperative
      morbidities in this series included 1 death from pulmonary embolism and 9 wound
      complications. Forty percent of the patients had normal bladder and bowel
      functions after surgery, while 60% of the patients had partial or complete loss
      of bladder and bowel functions. All but 2 patients in this group remained
      ambulatory after the surgery. The mean disease-free survival for patients with
      wide or marginal en bloc tumor excisions was 51 months, but the mean disease-free
      survival was only 17.5 months for patients who had contaminated/intralesional
      resections. CONCLUSION: Wide or marginal en bloc excision of sacral chordoma and
      chondrosarcoma is associated with significant improvement in disease-free
      survival with acceptable perioperative morbidity rate.

PMID- 19752712
TI  - Buchbinder R, Staples M, Jolley D. Doctors with a special interest in back pain
      have poorer knowledge about how to treat back pain. Spine. In press.

PMID- 19752714
TI  - Circumcision and risk of HIV infection in Australian homosexual men.
AB  - OBJECTIVE: To assess circumcision status as a risk factor for HIV seroconversion
      in homosexual men. DESIGN, SETTING AND PARTICIPANTS: The Health in Men (HIM)
      study was a prospective cohort of homosexual men in Sydney, Australia. HIV
      negative men (n = 1426) were recruited primarily from community-based sources
      between 2001 and 2004 and followed to mid-2007. Participants underwent annual HIV
      testing, and detailed information on sexual risk behaviour was collected every 6
      months. MAIN OUTCOME MEASURE: HIV incidence in circumcised compared with
      uncircumcised participants, stratified by whether or not men predominantly
      practised the insertive role in anal intercourse. RESULTS: There were 53 HIV
      seroconversions during follow-up; an incidence of 0.78 per 100 person-years. On
      multivariate analysis controlling for behavioural risk factors, being circumcised
      was associated with a nonsignificant reduction in risk of HIV seroconversion
      [hazard ratio 0.78, 95% confidence interval (CI) 0.42-1.45, P = 0.424]. Among one
      third of study participants who reported a preference for the insertive role in
      anal intercourse, being circumcised was associated with a significant reduction
      in HIV incidence after controlling for age and unprotected anal intercourse (UAI)
      (hazard ratio 0.11, 95% CI 0.03-0.80, P = 0.041). Those who reported a preference
      for the insertive role overwhelmingly practised insertive rather than receptive
      UAI. CONCLUSIONS: Overall, circumcision did not significantly reduce the risk of
      HIV infection in the HIM cohort. However, it was associated with a significant
      reduction in HIV incidence among those participants who reported a preference for
      the insertive role in anal intercourse. Circumcision may have a role as an HIV
      prevention intervention in this subset of homosexual men.

PMID- 19752713
TI  - Clinical epidemiology of HIV-associated end-stage renal failure in the UK.
AB  - OBJECTIVE: To describe the clinical epidemiology of HIV-associated end-stage
      renal failure (HIV/ESRF) from 1998 to 2007 in the United Kingdom. DESIGN:
      Observational cohort study. SETTING: Seven leading HIV centres and affiliated
      renal clinics in the United Kingdom. PARTICIPANTS: A total of 21 951 patients in
      whom renal function was measured. MAIN OUTCOME MEASURE: Development of end-stage
      renal failure (ESRF) as defined by initiation of permanent renal replacement
      therapy (pRRT). RESULTS: Sixty-eight (0.31%) patients had HIV/ESRF, 44 (64.7%) of
      whom were black. The prevalence of ESRF in black patients increased over time
      from 0.26% in 1998-1999 to 0.92% in 2006-2007 (P for trend = 0.001). Overall 5
      year survival from starting pRRT was 70.3%, and significantly better for black
      patients compared to those of other ethnicities (85.2 vs. 43.4%, P = 0.001). In
      multivariable analysis, black ethnicity was associated with a higher risk of ESRF
      [HR 6.93, 95% confidence interval (CI) 3.56, 13.48], whereas a higher current CD4
      cell count was associated with reduced risk (HR: 0.83, 95% CI 0.76, 0.95) per 50
      cells higher). No association was seen between current viral load or current
      highly active antiretroviral therapy (HAART) status and ESRF. On the basis of
      these observations, we estimate that 231 HIV-infected patients required pRRT in
      the United Kingdom in 2007, and an HIV prevalence of 0.51% among the United
      Kingdom pRRT recipients in that year. CONCLUSION: The prevalence of HIV/ESRF
      increased during the HAART era to reach nearly 1% in black patients, in whom
      favourable survival rates were observed. Earlier HIV diagnosis will be an
      important strategy to stem the rising trend of HIV/ESRF.

PMID- 19752716
TI  - Crack cocaine use increases the incidence of AIDS-defining events in French
      Guiana.
AB  - We conducted a retrospective cohort study to determine the influence of crack
      cocaine use on the outcomes of HIV infection. The use of crack cocaine was
      associated with an increased incidence of AIDS: 27.8 per 100 person-years versus
      6.6 per 100 person-years for nonusers, adjusted hazard ratio = 3.8 (1.9-7.5), P <
      0.001. More specifically, crack users had a greater incidence of disseminated
      histoplasmosis, pneumocystosis, pulmonary tuberculosis, bacterial pneumonia,
      oesophageal candidiasis, cerebral toxoplasmosis, salmonellosis, and genital
      herpes. The care of HIV-infected crack users is particularly challenging and
      requires additional efforts to reduce the high morbidity of these patients.

PMID- 19752717
TI  - Characteristics of non-Hodgkin lymphoma arising in HIV-infected patients with
      suppressed HIV replication.
AB  - OBJECTIVE: Despite effective treatment of HIV infection, some patients still
      develop non-Hodgkin lymphoma (NHL). We analysed patients with HIV-associated NHL
      and undetectable plasma HIV-RNA, according to the duration of HIV suppression.
      METHODS: Out of 388 patients included in a prospective cohort of HIV-associated
      NHL from 1996 to 2008, 128 (33%) had a plasma HIV-RNA below 500 copies/ml and
      were included in the study. Patients with long-term HIV suppression (>18 months)
      were compared with patients with recent HIV suppression (< or = 18 months).
      RESULTS: All patients but three were treated with combination antiretroviral
      therapy, with a median duration of 2.2 years. The median duration of HIV
      suppression was 10.1 months. Most cases (65%) occurred within 18 months following
      HIV suppression. In the more than 18 months group, patients developed NHL at a
      higher CD4 cell count than patients with 18 months or less of HIV suppression
      (359 versus 270 cells/microl, P = 0.02). None of the NHL characteristics were
      different between the two groups. Outcome was similar in the two groups (complete
      remission, 64 versus 72.5%; P = 0.35 and 3-year survival, 46 versus 56%; P =
      0.08). In addition, 52% of the tumours were Epstein-Barr virus or human
      herpesvirus 8 associated, without any difference in the proportion of virus
      associated tumours according to the duration of HIV suppression. CONCLUSION: In
      patients with undetectable HIV-RNA, NHL occurred mainly within the first 18
      months following HIV suppression. In patients developing NHL after long-term HIV
      suppression, the level of CD4 cell count was higher, but the association with
      Epstein-Barr virus or human herpesvirus 8 and the prognosis were similar to that
      observed in patients with recent HIV suppression.

PMID- 19752715
TI  - AIDS-related and non-AIDS-related mortality in the Asia-Pacific region in the era
      of combination antiretroviral treatment.
AB  - OBJECTIVE: Although studies have shown reductions in mortality from AIDS after
      the introduction of combination antiretroviral treatment (cART), little is known
      about cause-specific mortality in low-income settings in the cART era. We
      explored predictors of AIDS and non-AIDS mortality and compared cause-specific
      mortality across high-income and low-income settings in the Asia-Pacific region.
      METHODS: We followed patients in the Asia Pacific HIV Observational Database from
      the date they started cART (or cohort enrolment if cART initiation was identified
      retrospectively), until the date of death or last follow-up visit. Competing
      risks methods were used to estimate the cumulative incidence, and to investigate
      predictors, of AIDS and non-AIDS mortality. RESULTS: Of 4252 patients, 215 died;
      89 from AIDS, 97 from non-AIDS causes and 29 from unknown causes. Age more than
      50 years [hazard ratio 4.29; 95% confidence interval (CI) 2.10-8.79] and CD4 cell
      counts less than or equal to 100 cells/microl (hazard ratio 8.59; 95% CI 5.66
      13.03) were associated with an increased risk of non-AIDS mortality. Risk factors
      for AIDS mortality included CD4 cell counts less than or equal to 100
      cells/microl (hazard ratio 34.97; 95% CI 18.01-67.90) and HIV RNA 10 001 or more
      (hazard ratio 4.21; 95% CI 2.07-8.55). There was some indication of a lower risk
      of non-AIDS mortality in Asian high-income, and possibly low-income, countries
      compared to Australia. CONCLUSION: Immune deficiency is associated with an
      increased risk of AIDS and non-AIDS mortality. Older age predicts non-AIDS
      mortality in the cART era. Less conclusive was the association between country
      income level and cause-specific mortality because of the relatively high
      proportion of unknown causes of death in low-income settings.

PMID- 19752718
TI  - New treatment approaches in renal cell carcinoma.
AB  - Metastatic renal cell carcinoma (RCC) is notoriously chemoresistant; up until
      recently, immunotherapy (in particular interferon-alpha) has represented the
      treatment of choice. The understanding of the biology of RCC has resulted in the
      development of targeted therapies. In particular, multikinase inhibitors
      (sunitinib, sorafenib, axitinib, pazopanib), antivascular endothelial growth
      factor agents (bevacizumab), and mammalian target of rapamycin inhibitors
      (temsirolimus, everolimus) now have a role in the approach to different subsets
      of RCC. Sunitinib is indicated for the first-line therapy of metastatic RCC as a
      consequence of a positive phase III trial versus interferon-alpha; sorafenib is
      now registered for the second-line treatment of RCC, which was earlier treated
      with cytokine as a consequence of a positive phase III trial versus placebo.
      Bevacizumab is also indicated in the first-line treatment of metastatic RCC given
      in combination with interferon-alpha as a consequence of two positive phase III
      trials. Temsirolimus, unlike the other agents, has also shown activity in poor
      prognosis patients, and is now the treatment of choice in previously untreated
      poor-prognosis RCC as a single agent. Everolimus can be considered as the best
      therapeutic option in patients with RCC pretreated with targeted agents as a
      consequence of a positive phase III study versus best supportive care. Markers
      for appropriate treatment selection, combined use of targeted agents, treatment
      of special histologies, and adjuvant and neoadjuvant setting represent important
      special issues to be dealt with in future studies.

PMID- 19752719
TI  - Role of efflux pump activity in lapatinib/caelyx combination in breast cancer
      cell lines.
AB  - The aim of this study was to investigate, at preclinical level, efflux pump
      modulation induced by lapatinib, a small-molecule dual inhibitor of the epidermal
      growth factor receptor (EGFR), in HER2-negative or HER2-positive breast cancer
      cell lines (SkBr3 and BRC230). We also evaluated the cytotoxic activity and
      modulation of biomolecular cellular pathways regulated by caelyx and lapatinib,
      used singly or in combination, at concentrations corresponding to peak plasma
      level in the two cell lines. Lapatinib was active in the HER2-overexpressing cell
      line, SkBr3, but not in BRC230 cell line, which does not express HER2.
      Conversely, caelyx exerted a cytotoxic effect on both the cell lines.
      Simultaneous exposure to lapatinib and caelyx in SkBr3 cell line produced an
      additive cytotoxic effect with dephosphorylation of HER2 and EGFR, an
      upregulation of p21, and an induction of apoptosis through dephosphorylation of
      BAD and caspase cleavage. In BRC230, simultaneous treatment induced a synergistic
      effect that was because of, at least in part, an upregulation of p21. Lapatinib
      also blocked efflux pumps, such as the breast cancer resistance protein I by
      increasing the length of time in which caelyx was present in tumor cell
      cytoplasm, which led to caspase cleavage, BAD dephosphorylation, and apoptosis.
      Our data indicate that lapatinib used in combination with caelyx is active in
      HER2-expressing cells, probably because of lapatinib-induced dephosphorylation of
      the HER2-EGFR pathway, and also in non-HER2-expressing cells, possibly because
      lapatinib blocks efflux pump activity, increasing the length of time of
      intracellular exposure to caelyx and thereby increasing its cytotoxic effect.

PMID- 19752720
TI  - CD10 (Neutral Endopeptidase) Expression in Myoepithelial Cells of Salivary
      Neoplasms.
AB  - CD10 is a cell surface peptidase expressed in a wide variety of normal and
      neoplastic tissues, including breast myoepithelial cells. In salivary glands,
      expression of CD10 has only been used to identify neoplastic myoepithelial cells
      of pleomorphic adenomas and myoepithelial carcinomas. However, its accuracy in
      other salivary tumors with myoepithelial component has yet to be analyzed. We
      examined 72 salivary tumors with myoepithelial differentiation using
      immunohistochemical technique to detect CD10. In salivary glands, CD10 expression
      was not detected in myoepithelial cells. Only fibrocytes within the intralobular
      stroma were CD10 positive. In neoplastic myoepithelial cells, CD10 expression was
      found in 25.71% of benign and 32.43% of malignant neoplasms. When the different
      groups of tumors were compared, epithelial-myoepithelial carcinomas (EMEC) showed
      a stark contrast with the others (83.3% of cases with CD10 expression).
      Surprisingly, adenoid cystic carcinomas and basal cell adenomas were negative in
      100% of the cases. Myoepitheliomas, pleomorphic adenomas, and myoepithelial
      carcinomas were positive in 27.7%, 30.0%, and 40% of the cases, respectively. In
      conclusion, salivary neoplastic myoepithelial cells gain CD10 expression in
      relation to their normal counterparts. However, the gain of this protein is not a
      sensitive marker for detecting myoepithelial cells in the majority of the tumors,
      except for EMEC. The high expression of CD10 by this carcinoma can be a valuable
      tool to separate EMEC from the tubular variant of adenoid cystic carcinomas in
      small incisional biopsies, where the precise diagnosis may be impossible.

PMID- 19752721
TI  - Expression of CD133 in synovial sarcoma.
AB  - The development of synovial sarcoma, a translocationally defined soft tissue
      tumor of unknown histogenesis with considerable resistance to systemic therapy
      and a poor prognosis, may involve cancer stem-like cells. Recent studies suggest
      that synovial sarcoma arises from a primitive progenitor-type cell and have shown
      that synovial sarcomas contain subpopulations with enhanced tumorigenic
      potential; however, little is known about cancer stem-like cells in synovial
      sarcoma. Histologic and gene expression studies have reported features of
      synovial sarcoma that are reminiscent of neural development, suggesting that a
      neural cancer stem-like cell marker, such as CD133, may mark cancer stem-like
      cells in synovial sarcoma, allowing for further characterization. Here, the
      immunohistochemical expression of CD133 in primary synovial sarcoma tumor tissue
      and synovial sarcoma cell lines is determined. Subpopulations of CD133 expressing
      cells are present in all primary synovial sarcomas (5/5) and synovial sarcoma
      cell lines (3/3) examined. Histologically, CD133 positive cells are dispersed and
      seem to have dendritic processes. This study demonstrates the presence of CD133
      expressing cells in synovial sarcoma for the first time and validates 3 synovial
      sarcoma cell lines as models for further study of the CD133+ subpopulation. The
      relationship between CD133 expression and cancer stem-like cells suggests that
      CD133 expressing synovial sarcoma cells may represent cancer stem-like cells in
      synovial sarcoma, which has significant implications for understanding the
      pathogenesis of this tumor and developing effective therapies.

PMID- 19752722
TI  - Baclofen suppresses binge eating of pure fat but not a sugar-rich or sweet-fat
      diet.
AB  - Baclofen is a gamma-aminobutyric acid-B agonist that is known to reduce the
      intake of some drugs of abuse. Binge eating of sugar or fat has been shown to
      have behavioral and neurochemical similarities to drug abuse, and may be special
      cases suggestive of natural addiction. To determine whether a treatment for drug
      abuse would have an effect on binge eating, and if so, which type of food intake
      might be affected, this study compared the effects of baclofen on binge eating
      sucrose, fat, and a sweet-fat combination. Rats were maintained for 21 days on a
      schedule of 12-h daily access to (i) a 10% sucrose solution, (ii) vegetable fat,
      or (iii) a commercially available sweet-fat chow. A fourth group had only 2-h
      daily access to vegetable fat. All four experimental groups, plus a control
      group, had ad libitum access to water and standard rodent chow. Food intake was
      then measured after intraperitoneal administration of baclofen (0, 0.6, 1.0, or
      1.8 mg/kg). Results showed that although there was no effect of drug on standard
      chow intake of rats in any group, baclofen stimulated binge eating of sweet-fat
      food, suppressed binge eating of pure fat (vegetable shortening) in the group
      with 2-h access, and had no effect on sucrose binges. These results support
      earlier findings of a suppressive effect of baclofen on binge eating of fat and
      introduce a new finding that the drug differentially affects binge eating of
      sucrose and a sugar-fat combination.

PMID- 19752723
TI  - Allopregnanolone microinjected into the lateral septum or dorsal hippocampus
      reduces immobility in the forced swim test: participation of the GABAA receptor.
AB  - Allopregnanolone is a 5alpha-reduced metabolite of progesterone with actions on
      gamma-aminobutyric acid-A (GABAA) receptors that produce antidepressant-like
      effects. However, little is known about the target brain regions that mediate its
      antidepressant-like effects. In this study, allopregnanolone (2.0 MUg/0.3
      MUl/rat) or its vehicle (35% cyclodextrin solution) were microinjected into the
      lateral septum, septofimbrial, or dorsal hippocampus of male Wistar rats that had
      previously received intraperitoneal injections of either saline or the GABAA
      antagonist bicuculline (1.0 mg/kg), and its effects were evaluated in the open
      field and forced swim tests. Allopregnanolone microinjected into the lateral
      septum or dorsal hippocampus, but not septofimbrial nucleus, induced a longer
      latency to the first immobility and a shorter total immobility time in the forced
      swim test compared with vehicle. Bicuculline pretreatment reversed the effect of
      allopregnanolone. None of the treatments produced significant changes in
      crossings in the open field test. In conclusion, allopregnanolone produces an
      antidepressant-like effect in rats submitted to the forced swim test through
      actions on GABAA receptors located in the lateral septum and dorsal hippocampus,
      which is consistent with the antistress effect of GABAA agonists in these
      particular brain structures.

PMID- 19752724
TI  - Modafinil and gamma-hydroxybutyrate have sleep state-specific pharmacological
      actions on hypocretin-1 physiology in a primate model of human sleep.
AB  - Hypocretin-1 is a hypothalamic neuropeptide that is important in the regulation
      of wake and the lack of which results in the sleep disorder narcolepsy. Using a
      monkey that has consolidated wake akin to humans, we examined pharmacological
      manipulation of sleep and wake and its effects on hypocretin physiology. Monkeys
      were given the sleep-inducing gamma-hydroxybutyrate (GHB) and the wake-inducing
      modafinil both in the morning and in the evening. Cerebrospinal fluid hypocretin
      1 concentrations changed significantly in response to the drugs only when
      accompanied by a behavioral change (GHB-induced sleep in the morning or modafinil
      induced wake in the evening). We also found that there was a large (180-fold)
      interindividual variation in GHB pharmacokinetics that explains variability in
      sleep induction in response to the drug. Our data indicate that the neurochemical
      concomitants of sleep and wake are capable of changing the physiological output
      of hypocretin neurons. Sleep independent of circadian timing is capable of
      decreasing cerebrospinal fluid hypocretin-1 concentrations. Furthermore,
      hypocretin neurons do not seem to respond to an 'effort' to remain awake, but
      rather keep track of time spent awake as a wake-promoting counterbalance to
      extended wakefulness.

PMID- 19752725
TI  - Lung isolation techniques for patients with difficult airway.
AB  - PURPOSE OF REVIEW: One-lung ventilation in the thoracic surgical patient can be
      achieved with the use of a double-lumen endotracheal tube or an independent
      bronchial blocker. A number of patients requiring lung isolation have a
      potentially difficult airway because of previous radiation to the neck or
      previous surgery to the tongue and larynx. This review will focus on the
      management of patients who have a difficult airway and require lung isolation.
      RECENT FINDINGS: Identification of the potentially difficult airway during the
      preoperative evaluation allows the preplanning and selection of the appropriate
      lung isolation device. Common devices used to achieve one-lung ventilation in
      patients with difficult airways include independent bronchial blockers (Arndt,
      Cohen, and Fuji Uniblocker). SUMMARY: In patients who require one-lung
      ventilation and who present with a difficult airway, the safest way to establish
      an airway is by placing a single-lumen endotracheal tube orally or nasotracheally
      while the patient is awake with the aid of a flexible fiberoptic bronchoscope.
      Lung isolation in these patients then is achieved by using an independent
      bronchial blocker; an alternative technique is to use a double-lumen endotracheal
      tube while using an airway catheter exchange technique. For the patient with a
      tracheostomy in place, an independent bronchial blocker is recommended.

PMID- 19752726
TI  - Control of perioperative muscle strength during ambulatory surgery.
AB  - PURPOSE OF REVIEW: This review describes strategies to control perioperative
      muscle strength in patients undergoing ambulatory surgery. RECENT FINDINGS:
      Although it is impossible to improve muscle relaxation (defined as absence of
      electrical activity) of intact resting muscle by hypnotics, analgesia is required
      to prevent pain-evoked muscular contractions during surgery. Regional anesthesia,
      as well as hypnotics and opioids, promotes intraoperative muscle relaxation.
      Neuromuscular blocking agents (NMBAs) induce dose-dependent muscle relaxation,
      but their effects vary widely between individuals, and postoperative residual
      curarization (PORC) exposes patients to additional risk. Low doses of NMBAs
      should, therefore, be used, effects be monitored quantitatively by
      acceleromyography, and residual neuromuscular block be reversed.
      Acetylcholinesterase inhibitor reversal can cause respiratory side effects, so
      the lowest efficacious dose should be used: as little as 0.015-0.025 mg kg(-1) of
      neostigmine is required at a train-of-four count of four with minimal fade.
      Sugammadex encapsulates steroidal NMBAs. Sugammadex reversal is a viable approach
      to rapidly antagonize deep levels of neuromuscular block. SUMMARY: Optimal muscle
      relaxation for ambulatory surgery results from a judicious combination of
      regional anesthesia, opioids, and low doses of NMBAs. The effects of NMBAs should
      be monitored quantitatively by acceleromyography and reversed appropriately.

PMID- 19752727
TI  - New advances in cardiac computed tomography.
AB  - PURPOSE OF REVIEW: Applications of computed tomography (CT) for cardiac imaging
      have evolved rapidly with the introduction of new hardware. These advances
      require a technology update, particularly as the new scanners have novel, unique
      features. This review focuses on post-64 generation CT scanner capabilities and
      novel clinical research applications enabled by these technologies. RECENT
      FINDINGS: By the release date of multicenter publications to evaluate 64-detector
      row coronary CT, new technology advanced the state of the art in terms of key
      metrics such as temporal resolution and volume coverage. Moreover, cardiac CT
      protocols continue to evolve and spark new applications. CT is now being used for
      plaque detection and is being applied for stress perfusion imaging. In addition,
      scanners have novel strategies for single heartbeat whole coronary imaging; this
      has enabled evaluations of endothelial shear stress and differences in coronary
      contrast opacification at a single point in time. SUMMARY: Continuous
      improvements in technology have moved CT beyond 64-detector rows. Understanding
      these technical specifications will enable evaluation of current and future
      applications for noninvasive cardiac imaging.

PMID- 19752728
TI  - Evolving concepts in selecting optimal strategies for the management of patients
      with stable coronary disease: pharmacologic or revascularization therapy.
AB  - PURPOSE OF REVIEW: Initial management of patients with stable ischemic heart
      disease (SIHD) continues to be vigorously debated amongst cardiologists. Despite
      the lack of robust data to support percutaneous coronary intervention (PCI) as
      the initial management of SIHD patients, it remains one of the most commonly
      performed procedures. Results of the Clinical Outcomes Utilizing
      Revascularization and Aggressive Drug Evaluation (COURAGE) trial reignited the
      controversy of the benefit of routine initial PCI over optimal medical therapy
      (OMT). RECENT FINDINGS: The trial suggested that, as an initial management
      strategy in patients with SIHD, PCI did not reduce the risk of death, myocardial
      infarction, or any other major cardiovascular events, when added to OMT. A meta
      analysis from Schomig et al. suggests that a PCI-based invasive strategy may
      improve long-term survival compared with solely medical treatment in stable
      coronary artery disease patients. CONCLUSION: As the ability to mechanically
      dilate obstructive coronary arterial stenoses has vastly improved our approach to
      managing patients with SIHD, the result has been a swing from an initial
      pharmacologic approach. An improved understanding of the pathophysiology of acute
      coronary syndrome, increased insight into plaque and patient vulnerability has
      led to the more aggressive use of appropriately targeted pharmacologic agents and
      an evolution in what constitutes OMT, based largely on the results of the COURAGE
      trial. Recent studies support the concept that, in SIHD patients, OMT alone
      compares favorably with a therapeutic strategy combining OMT with mechanical
      intervention. Thus, the treatment pendulum may be swinging back to the
      understanding that 'best practice' today requires the judicious use of
      interventional and medical therapies in the appropriate patient population.

PMID- 19752729
TI  - Ophthalmic manifestations of endocrine disorders: approaches and medical
      management.
AB  - PURPOSE OF REVIEW: Disorders of the endocrine system may present with various
      ophthalmic signs, symptoms, and pathology. Early detection, prevention, and
      monitoring of these manifestations can significantly benefit morbidity associated
      with such disease states including permanent visual dysfunction. RECENT FINDINGS:
      Several studies highlight the importance of early diagnosis in reducing the long
      term complications associated with these endocrine conditions, although these
      observations are mostly based on case reports and case series. SUMMARY: This
      review will focus on the connection of endocrine-related disease states with the
      development of specific ophthalmic pathology and is geared towards the general
      medical practitioner. The focus of the treating physician should be on
      facilitating early diagnosis to prevent potentially blinding complications.

PMID- 19752730
TI  - Tubulointerstitial nephritis and uveitis syndrome.
AB  - PURPOSE OF REVIEW: Tubulointerstitial nephritis and uveitis syndrome (TINU) is a
      specific form of intraocular inflammation (uveitis) combined with kidney disease
      that was first described in two patients by Dobrin et al. in 1975. Since then,
      approximately 200 more cases have been published. The cause of the disease is
      still unknown. A hypersensitivity reaction is suspected, especially an infection
      or very rarely a medication reaction is thought to trigger the disease. It is
      considered to be a rare disease and thus unfortunately is still unfamiliar to
      most ophthalmologists. Therefore, it is frequently overlooked in the differential
      diagnosis. In this review we want to show advances in diagnostics and treatment
      as well as progress in deciphering the pathogenesis. RECENT FINDINGS: Beta-2
      microglobulin (Ub2MG) analysis in urine and human leukocyte antigen (HLA) typing
      is helpful to diagnose TINU cases. A high association of HLA-DRB1*01 has been
      shown with TINU. A first single case report suggests a common antibody production
      against ocular and renal proteins. SUMMARY: TINU is a common cause of uveitis
      among patients who present with bilateral, anterior uveitis of sudden onset. It
      is more frequent in children and apparently in boys. Although the activity of the
      eye disease can persist for many months, it is usually controlled with little
      treatment and the outcome is very good.

PMID- 19752731
TI  - Mediating various direct-effect approaches.

PMID- 19752732
TI  - Mental vulnerability and survival after cancer.
AB  - BACKGROUND: It has been hypothesized that personality traits affect survival
      after cancer, but studies have produced inconsistent results. This study examined
      the association between mental vulnerability and survival after cancer in Denmark
      in a prospective cohort study. METHODS: Between 1976 and 2001, 12733 residents of
      Copenhagen completed a questionnaire eliciting information on a 12-item mental
      vulnerability scale, as well as various personal data. Follow-up in the Danish
      Cancer Registry until 2003 identified 884 incident cases of primary cancer, and
      follow-up for death from the date of cancer diagnosis until 2003 identified 382
      deaths. Mental vulnerability scores were divided into 4 approximately equal-sized
      groups. Cox proportional hazards regression models were used to estimate the
      hazard ratio (HR) of all-cause mortality. RESULTS: Multivariate HR for all-cause
      mortality for persons in the highest category of mental vulnerability compared
      with those at the lowest was 1.1 (95% confidence interval = 0.9-1.5). CONCLUSION:
      We found no support for the hypothesis that mental vulnerability is associated
      with survival after cancer diagnosis.

PMID- 19752733
TI  - Maternal exposure to the Dutch famine before conception and during pregnancy:
      quality of life and depressive symptoms in adult offspring.
AB  - BACKGROUND: Gestational exposure to famine has been associated with several
      chronic diseases in adulthood, but few studies in humans have related prenatal
      famine exposure to health-related quality of life. We used the circumstances of
      the Dutch Famine of 1944-1945 (during which official rations were <900 kcal/day
      for 24 weeks) to assess whether exposure to famine prior to conception or at
      specified stages of pregnancy was related to self-reported health-related quality
      of life and depressive symptoms in adulthood. METHODS: We studied 923
      individuals, including persons born in western Holland between January 1945 and
      March 1946, persons born in the same 3 institutions in 1943 and 1947 and same-sex
      siblings of persons in series 1 or 2. Between 2003 and 2005 (mean age: 59 years),
      we assessed self-reported quality of life with the Short Form 36 questionnaire
      and derived mental and physical component scores. Depressive symptoms were
      assessed with the Center for Epidemiologic Studies Depression scale. RESULTS:
      Mean mental and physical component scores were 52.4 (SD = 9.4) and 48.9 (9.0),
      respectively. The mean depression score was 11.6 (7.4). Age-, sex-, and schooling
      adjusted estimates for mutually adjusted exposures were -2.48 for the mental
      component score with exposure before conception (95% confidence interval = -4.46
      to -0.50) and 0.07 with exposure during pregnancy (-1.15 to 1.29). Adjusted
      estimates for the physical component score were 1.26 with exposure before
      conception (-0.67 to 3.19) and -0.73 with exposure during pregnancy (-1.94 to
      0.48). Adjusted estimates for the depression score were 2.07 with exposure before
      conception (0.60 to 3.54) and 0.96 with exposure during pregnancy (0.09 to 1.88).
      There was no evidence of heterogeneity of effects by specific periods of
      pregnancy exposed to famine. CONCLUSIONS: A mother's exposure to famine prior to
      conception of her offspring was associated with lower self-reported measures of
      mental health and quality of life in her adult offspring.

PMID- 19752734
TI  - Cumulative lead dose and cognitive function in older adults.
AB  - BACKGROUND: The current population of older Americans has accumulated substantial
      lifetime lead doses, which raises concern about the possibility of adverse
      cognitive outcomes. We evaluated whether cumulative lead dose from environmental
      exposures is associated with cognitive function and decline, and whether such
      effects are persistent, reversible, or progressive. METHODS: We used longitudinal
      linear modeling to evaluate associations of tibia lead concentration with
      cognitive function and decline in sociodemographically diverse, community
      dwelling adults aged 50-70 years who were randomly selected from neighborhoods in
      Baltimore. Six summary measures of cognitive function were created from standard
      tests in the following domains: language, processing speed, eye-hand
      coordination, executive functioning, verbal memory and learning, and visual
      memory. RESULTS: The mean (SD) tibia lead level was 18.8 (11.6) microg/g. In
      models adjusted for demographic characteristics, socioeconomic status (SES), and
      race/ethnicity, higher tibia lead was associated with a progressive decline in
      eye-hand coordination. Tibia lead was associated with persistently impaired
      cognitive function in all 6 domains, although these associations weakened after
      increasing covariate control. In fully adjusted stratified analysis among white
      persons, persistent effects were apparent in eye-hand coordination, executive
      functioning, and verbal memory and learning. CONCLUSIONS: The study presents the
      strongest evidence to date of the effects of cumulative lead dose on adult
      cognitive function independent of SES. The study population was relatively young
      and the average total duration of follow-up short (<30 months); these findings
      may represent the lower bound of the impact of cumulative lead dose on cognitive
      function of older adults.

PMID- 19752735
TI  - Carotid intima-media thickness measurement in cardiovascular screening
      programmes.
AB  - Support for the notion that a carotid intima-media thickness (CIMT) measurement
      is useful in individual cardiovascular risk prediction in addition to a risk
      function may come from studies showing that for an individual a high or low CIMT
      measurement leads to a correct shift from one to another risk category and this
      shift is followed by different treatment consequences. We set out to
      systematically review the published evidence by performing a PubMed search (2
      March 2009). Out of 50 publications on CIMT and future events, 31 reported on the
      relation in the correct domain, [i.e. those free from symptomatic vascular
      disease or diabetes mellitus in which assessment of risk using a risk function
      (e.g. Framingham or SCORE) to base initiation of drug treatment upon is
      recommended]. Most studies reported relative risks (or equivalents) for the
      entire population only, and no information on relative risks within certain risk
      categories that may be of use to reclassify individuals based on combination of
      absolute and relative risks. No data on potential shifts of participants was
      presented. Eight studies specifically focused on the added value of CIMT in risk
      prediction. In seven studies the area under the curve (AUC) of a receiver
      operating characteristic was used to assess improvements in risk prediction.
      These analyses showed that addition of a CIMT measurement to established risk
      factors led to small and sometimes significant improvements in the AUC. However,
      change in AUC should not be the only parameter to rely on to judge the
      appropriateness of CIMT in risk stratification. In one study (n = 242), evidence
      was presented in participants with an intermediate Framingham risk score, a CIMT
      measurement above the 60th (men) and 80th (women) percentile of age-specific
      normal CIMT values, shifted participants above the threshold for initiation of
      drug therapy. Yet, the study was based on 24 events, and no information was
      presented on the proportion of participants correctly shifted. At present it
      seems that the published evidence to quantitatively support the use of a CIMT
      measurement to help in risk stratification on top of a risk function is limited.

PMID- 19752736
TI  - Incidence and mortality by colorectal cancer in Spain during 1951-2006 and its
      relationship with behavioural factors.
AB  - Incidence of colorectal cancer has steadily increased in both the sexes and
      across all age groups during the last decades in Spain, in contrast with other
      countries where incidence decreased during this period. This increase is more
      marked among men, probably due to a high exposure to risk factors such as
      smoking, heavy drinking, overweight and diabetes. Annual age-adjusted mortality
      rates have increased in Spain during the period 1951-2000, but from that time
      until 2006 these rates have kept steady in males and fallen in females. When
      analyzing the evolution of exposure to behavioural factors during this period,
      known as risk or protective factors for colorectal cancer in Spain, notorious
      increases in tobacco and alcohol consumption, red and processed meats intake and
      a decreased ingestion of vegetables, cereals and beans were observed. Cigarette
      smoking, alcohol consumption, red meats, poultry, fish, vegetables and fruit were
      highly, positively correlated with colorectal cancer incidence and mortality, and
      cereals and beans consumption showed strong, negative correlations. At the same
      time and during this period, physical exercise decreased and overweight, obesity
      and diabetes mellitus notably increased. Certain changes in diet and lifestyle
      can be attributed to the growth in income during the last decades, but the lack
      and delay in implementing legislative and educational measures by the State and
      Regional Governments during decades cannot be ignored. In colorectal cancer, a
      minimal time span of 10-15 years is necessary for changes in exposure to risk
      factors to be able to modify the incidence of the tumour. Therefore, the
      implementation of more vigorous legislative and educational measures in Spain
      against smoking, heavy drinking, red meat intake, sedentary lifestyle, overweight
      and others reviewed in this study, is urgent.

PMID- 19752737
TI  - Evaluation of a breast/ovarian cancer genetics referral screening tool in a
      mammography population.
AB  - PURPOSE: Simple screening tools are needed to facilitate the appropriate referral
      of patients for genetic counseling and testing for BRCA1/2 mutations. This study
      evaluated the reliability and accuracy of a "referral screening tool" designed
      for rapid identification of individuals at potential hereditary risk for
      breast/ovarian cancer. METHODS: The referral screening tool was administered to
      2464 unselected women undergoing screening mammography. Detailed four-generation
      cancer pedigrees were collected by telephone interview on a random subset of 296
      women. The pedigrees were analyzed using four established hereditary risk models
      (BRCAPRO, Myriad II, BOADICEA, FHAT), with a > or =10% BRCA1/2 mutation
      probability or a FHAT score of > or =10 as the definition of "high risk."
      RESULTS: The referral screening tool identified 6.2% of subjects as screen
      "positive" (high risk). Concordance of randomly repeated referral screening tools
      (156 of 2464) was 96% (kappa = 0.75). In comparison with the pedigree analyses,
      the referral screening tool demonstrated an overall (high risk by any model)
      sensitivity of 81.2%, specificity of 91.9%, and discriminatory accuracy of 0.87.
      CONCLUSIONS: Within the population studied, the referral screening tool seems to
      be a reliable and valid tool to identify individuals who should be referred for
      consideration of BRCA1/2 testing. Further examination of the referral screening
      tool in primary care settings is warranted to assess its impact on the efficiency
      with which health care providers triage patients to cancer genetics services.

PMID- 19752738
TI  - Immunohistochemistry staining for the mismatch repair proteins in the clinical
      care of patients with colorectal cancer.
AB  - PURPOSE: The Ohio State University was one of the first medical centers to begin
      routinely performing immunohistochemical staining for the four mismatch repair
      proteins (MLH1, MSH2, MSH6, and PMS2) on all newly diagnosed patients with
      colorectal cancer. The results of implementing this testing on a clinical basis
      are critically assessed. METHODS: From March 1, 2006, to March 31, 2008, 270
      newly diagnosed colorectal cancer tumors received immunohistochemical staining
      for MLH1, MSH2, MSH6, and PMS2. If any stain was absent, the cancer genetic
      counselors were alerted, so that they could contact the patient. A follow-up
      genetic consultation was recommended for all patients with any stain absent other
      than MLH1 and to patients with absence of MLH1 +/- PMS2 who were diagnosed
      younger than 60 years had a multiple Lynch syndrome-associated cancers or had a
      first-degree relative with colorectal cancer or endometrial cancer. Those
      attending the genetic consultation were offered appropriate follow-up testing.
      RESULTS: There were 57 (21.1%) cases with abnormal immunohistochemical results.
      Genetics was able to contact 54 (94.7%) of these patients. It was determined that
      34 (62.9%) of these 54 patients should be referred for a cancer genetics
      consultation, however, only nine (26.5%) made an appointment. Seven of the nine
      underwent additional testing, which was informative in five of the patients. Two
      (0.7%) new cases of Lynch syndrome were diagnosed and three patients were found
      to have proven/probable MLH1 promoter methylation. CONCLUSIONS: Routine
      immunohistochemical of the mismatch repair proteins on all newly diagnosed
      patients with colorectal cancer can be implemented clinically, however, patient
      uptake of follow-up genetic consultation is lower than expected.

PMID- 19752739
TI  - Comparative effectiveness research and genomic medicine: an evolving partnership
      for 21st century medicine.
AB  - The American Recovery and Reinvestment Act has provided resources for comparative
      effectiveness research that will lead to evidence-based decisions about health
      and health care choices. Some have voiced concerns that evidence-based
      comparative effectiveness research principles are only relevant to "average"
      patients and not as much to individuals with unique combinations of genes,
      exposures and disease outcomes, intrinsic to genomic medicine. In this
      commentary, we argue that comparative effectiveness research and genomic medicine
      not only can and should coexist but also they will increasingly benefit from each
      other. The promise and success of genomic medicine will depend on rigorous
      comparative effectiveness research to compare outcomes for genome-based
      applications in practice to traditional non-genome-based approaches. In addition,
      the success of comparative effectiveness research will depend on developing new
      methods and clinical research infrastructures to integrate genome-based
      personalized perspectives into point of care decisions by patients and providers.
      There is a need to heal the apparent schism between genomic medicine and
      comparative effectiveness research to enhance knowledge-driven practice of
      medicine in the 21st century.

PMID- 19752740
TI  - Increasing the diagnostic value of evoked potentials in multiple sclerosis by
      quantitative topographic analysis of multichannel recordings.
AB  - SUMMARY: This study presents a method to record and analyze multichannel visual
      evoked potential (VEP) and somatosensory-evoked potential (SEP) in an objective,
      automatic, and quantitative manner. The intention of this study was to assess
      their diagnostic value in multiple sclerosis (MS). A 256-channel VEP and SEP were
      recorded in 44 healthy subjects, 26 patients with MS, and 20 patients with other
      neurologic diseases. Topographic pattern recognition methods were applied and a
      normative database was established. Z-score statistics allowed identifying the
      number of subjects with significant abnormal values in each group. These values
      were compared with conventional single-channel waveform analysis. The diagnostic
      value of the new measures for MS reached a sensitivity of 72% and a specificity
      of 100% for the VEP, which was significantly higher than the conventional
      analysis. For the SEP, the specificity was also high (93%) but the sensitivity
      remained low as in the conventional analysis (30%). The quantitative topographic
      analysis of multichannel VEP revealed high-diagnostic sensitivity and specificity
      for MS. Moreover, the method reliably identified the most dominant VEP and SEP
      components in the healthy subject group. The results indicate that objective
      topographic analysis of multichannel recordings increase the value of VEP as
      surrogate marker for MS.

PMID- 19752741
TI  - Use of routine MEG in the primary diagnostic process of epilepsy.
AB  - At present, in epilepsy, magnetoencephalography (MEG) is mostly used for
      presurgical evaluations. It has proven to be robust for detecting and localizing
      interictal epileptiform discharges. Whether this is also true for first-line
      investigation in the diagnosis of epilepsy has not been investigated yet. We
      present our data on the usefulness of MEG in the earliest phase of diagnosing
      epilepsy. We examined 51 patients with suspicion of neocortical epilepsy and an
      inconclusive routine EEG. A method to integrate MEG in daily routine was
      developed. Results of visually assessed MEG recordings were compared,
      retrospectively, with clinical data and with the results of EEG after sleep
      deprivation. After a finding of inconclusive, routine MEG generated a gain in
      diagnostic value of 63% when compared with "final" clinical diagnosis. This is
      comparable with the added value of EEG after sleep deprivation recorded
      previously in the same patients. However, MEG is less of a burden for patient and
      hospital and has no association with risk of increase in seizure frequency. The
      routine MEG with visual assessment only is a reliable diagnostic tool in the
      routine diagnosis of epilepsy and may replace or precede EEG after sleep
      deprivation in daily clinical practice. Furthermore, MEG together with MRI
      enables magnetic source imaging and, thus, may provide additional information on
      the cortical localization of the epilepsy of a patient.

PMID- 19752742
TI  - Reliability of superficial peroneal, sural, and medial plantar nerve conduction
      studies: analysis of statistical methods.
AB  - The reliability of medial plantar, sural, and superficial peroneal nerve
      conduction studies (NCS) has not been widely studied. These nerves are usually
      involved in distal sensory neuropathies and their serial study is relevant in the
      clinical setting. PURPOSE: To determine the inter- and intrarater reliability of
      superficial peroneal, sural, and medial plantar NCS in healthy participants.
      METHODS: Two raters performed the bilateral NCS twice in 20 healthy participants
      (23.5 +/- 3.5 years). Reliability was analyzed by the Bland-Altman method and
      intraclass correlation coefficient (ICC). Variability was established by the
      coefficient of variation. RESULTS: The Bland-Altman method showed a good level of
      intra- and interrater agreement for all nerves. The amplitude (rater 1) and
      latency of the medial plantar nerve and the amplitude of the sural nerve (rater
      2) had an intrarater ICC of >or=0.75. Interrater analysis showed concordance
      levels between moderate and very low. The highest coefficients of variations were
      found for amplitude and the lowest for nerve conduction velocity. CONCLUSIONS:
      Although the Bland-Altman method confirmed a good intra- and interrater
      reliability of the studied nerves, ICC analyses showed mixed results. These
      statistical approaches are complementary, and each one has advantages and
      disadvantages that must be considered in their application and interpretation.

PMID- 19752743
TI  - Cingulate lesions presenting with epileptic spasms.
AB  - PURPOSE: To describe the novel finding of epileptic spasms arising from a
      cingulate lesion. METHODS: We describe two children presenting with epileptic
      spasms who had lesions of the cingulate gyrus on MRI. RESULTS: In both patients,
      the lesions involved the midcingulate cortex. Seizures were characterized by
      prominent motor manifestations and resembled spasms. Both patients had a complete
      resolution of seizures after resection of their cingulate lesions. DISCUSSION:
      Cingulate seizures can present with a variety of behaviors including complex
      motor manifestations, vocalizations, and autonomic changes. Lesions in the
      midcingulate cortex can also produce epileptic spasms.

PMID- 19752744
TI  - Effects of seizures on cardiac function.
AB  - Various chronic and acute autonomic effects on the heart are seen during
      epileptic seizures, and some have been implicated in cases of sudden unexpected
      death in epilepsy (SUDEP). Chronic autonomic dysfunction, either congenital or
      acquired through seizures or medications, and structural changes of the heart may
      all predispose patients to SUDEP. Acute autonomic changes during seizures, in
      particular ictal bradycardia or transient ischemia, may indicate an increased and
      preventable risk of mortality in patients with epilepsy. However, there is no
      definite epidemiologic evidence associating any of the chronic or acute cardiac
      effects of seizures with SUDEP. Cases of SUDEP and near-SUDEP recorded during
      long-term electroencephalography monitoring offer some insight into the potential
      mechanisms leading to SUDEP. These cases suggest that autonomic instability
      ending in cardiorespiratory arrest may be provoked by postictal suppression
      rather than by ictal activation of the autonomic nervous system. Additional
      epidemiologic studies on high-risk populations and access to recorded cases of
      SUDEP may provide more details about the exact sequence of events leading to
      death and thus guide the development of possible preventive strategies.

PMID- 19752745
TI  - No correlation between clinical response to CTLA-4 blockade and presence of NY
      ESO-1 antibody in patients with metastatic melanoma.

PMID- 19752746
TI  - Vaccination of melanoma patients with Melan-A/Mart-1 peptide and Klebsiella outer
      membrane protein p40 as an adjuvant.
AB  - Toll-like receptor ligands are potentially useful adjuvants for the development
      of clinical T cell vaccination. Here we investigated the novel Toll-like
      receptor2 ligand P40, the outer membrane protein A derived from Klebsiella
      pneumoniae. Seventeen human leukocyte antigen-A*0201 positive stage III/IV
      melanoma patients were vaccinated with P40 and Melan-A/Mart-1 peptide
      subcutaneously in monthly intervals. Adverse reactions were mild-to-moderate.
      Fourteen patients received at least 8 vaccinations and were thus evaluable for
      clinical tumor and immune responses. Seven patients experienced progressive
      disease, whereas 2 patients had stable disease throughout the trial period, 1 of
      them with regression of multiple skin metastases. The remaining 5 patients had no
      measurable disease. Melan-A/Mart-1 specific CD8 T cells were analyzed ex vivo,
      with positive results in 6 of 14 evaluable patients. Increased percentages of T
      cells were found in three patients, memory/effector T cell differentiation in 4
      patients, and a positive interferon-gamma Elispot assay in 1 patient. Antibody
      responses to P40 were observed in all patients. We conclude that vaccination with
      peptide and P40 was feasible and induced ex vivo detectable tumor antigen
      specific T cell responses in 6 of 14 patients with advanced melanoma.

PMID- 19752747
TI  - Impact of a recombinant fowlpox vaccine on the efficacy of adoptive cell therapy
      with tumor infiltrating lymphocytes in a patient with metastatic melanoma.
AB  - A patient with metastatic melanoma who had progressive disease after prior
      surgical resections, high dose interleukin-2, and anti-cytotoxic T lymphocyte
      antigen-4 antibody received sequential treatments with autologous tumor
      infiltrating lymphocytes that recognized the gp100 melanocyte differentiation
      antigen. Although no clinical response was seen when cells were administered
      alone, an objective clinical response to therapy was seen with tumor infiltrating
      lymphocytes administered together with a highly immunogenic fowlpox vaccine
      expressing a gp100: 209-217 (210M) epitope. Persistence of the transferred
      antigen-specific lymphocytes in the peripheral blood was observed only after
      adoptive cell therapy plus administration of vaccine. Cell proliferation in vitro
      was further stimulated by additional vaccine and interleukin-2. The patient has
      an ongoing partial response at 10 months after the last treatment.

PMID- 19752748
TI  - Priming and activation of human ovarian and breast cancer-specific CD8+ T cells
      by polyvalent Listeria monocytogenes-based vaccines.
AB  - Immunotherapeutic vaccine is potentially an effective strategy to combat cancer.
      Essential components of an effective vaccine must include antigens that are
      processed by the major histocompatibility complex class I pathway, presented by
      the tumor major histocompatibility complex molecules, and an effective antigen
      delivery platform that is capable of breaking self-tolerance. In this study, we
      characterized a set of ovarian cancer-specific T-cell epitopes delivered by live
      attenuated recombinant Listeria monocytogenes (Lm DeltaactADeltainlB) as a
      vaccine vector. We present data that peptide-specific T cells recognize the human
      monocytic cell line THP-1 infected with recombinant Lm DeltaactADeltainlB
      encoding the epitopes. Furthermore, we demonstrate that recombinant L.
      monocytogenes (Lm)-infected antigen-presenting cells can prime and expand epitope
      specific CD8 T cells in vitro and such CD8 T cells recognize not only peptide
      loaded targets but also ovarian and breast tumor cells presenting endogenous
      epitopes. Finally, peptide-specific T cells generated using peripheral blood
      mononuclear cell from ovarian cancer patients recognize target cells infected
      with recombinant Lm DeltaactADeltainlB encoding the epitopes. Our results
      demonstrate that live-attenuated recombinant Lm can be used effectively as a
      vehicle to deliver cancer peptide antigens singly or as a multiepitope construct.
      Thus, the use of recombinant live-attenuated Lm strains encoding endogenously
      processed and presented tumor epitopes/antigens represents an attractive strategy
      for active cancer immunotherapy in a clinical setting.

PMID- 19752749
TI  - Development of an Escherichia coli expressing listeriolysin-O vaccine against
      Wilms tumor gene 1-expressing tumors.
AB  - Through their ability to induce cytotoxic T-lymphocytes and inhibit Foxp3 T
      regulatory cells, Escherichia coli expressing listeriolysin-O (LLO) and a model
      tumor antigen have been shown to exert strong antitumor activity. The aim of this
      study is to extend these observations to a self-protein and clinically relevant
      tumor antigen associated with most types of adult leukemia: Wilms tumor gene 1
      (WT1). We demonstrate that an E. coli coexpressing LLO and WT1 is capable of
      inducing a strong antitumor effect against WT1-expressing tumors in vivo through
      its ability to induce cytotoxic T-lymphocytes and inhibit the function of Foxp3 T
      regulatory cells. Furthermore, we have characterized the immunodominant epitope
      involved in this effect (NAPYLPSCL) and demonstrated that coinjection of
      NAPYLPSCL with E. coli-LLO resulted in an antitumor effect largely equivalent to
      that obtained with E. coli-LLO/WT1. Our data demonstrate that the results
      obtained with a clinically irrelevant model tumor antigen remain valid with a
      "real" tumor antigen and that the adjuvant properties of the E. coli-LLO vaccine
      can be exploited in conjunction with peptides. The results obtained in this study
      will facilitate the translation of this work to human studies by combining
      antigenic motifs relevant to specific human leukocyte antigen haplotypes with the
      adjuvant effect of E. coli-LLO.

PMID- 19752750
TI  - Genome-wide mapping of PiggyBac transposon integrations in primary human T cells.
AB  - The piggyBac transposon system represents a promising nonviral tool for gene
      delivery and discovery, and may also be of value for clinical gene therapy.
      PiggyBac is a highly efficient integrating vector that stably transfects
      (approximately 40%) of primary human T cells for potential adoptive immunotherapy
      applications. To evaluate the potential genotoxicity of piggyBac, we compared 228
      integration sites in primary human T cells to integrations in 2 other human
      derived cell lines (HEK293 and HeLa) and randomly simulated integrations into the
      human genome. Our results revealed distinct differences between cell types.
      PiggyBac had a nonrandom integration profile and a preference for transcriptional
      units (approximately 50% into RefSeq genes in all cell types), CpG islands (18%
      in T cells and 8% in other human cells), and transcriptional start sites (<5 kb,
      16% to 20% in all cell types). PiggyBac also preferred TTAA but not AT-rich
      regions of the human genome. We evaluated the expression of mapped genes into
      which piggyBac integrated, and found selection of more active genes in primary
      human T cells compared with other human cell types, possibly due to concomitant T
      cell activation during transposition. Importantly, we found that in comparison to
      what has been reported for gammaretroviral and human lenitviral vectors, piggyBac
      had decreased integration frequency into or within 50 kb of the transcriptional
      start sites of known proto-oncogenes. Hence the piggyBac nonviral gene delivery
      system seems to represent a promising gene transfer system for clinical
      applications using human T lymphocytes.

PMID- 19752751
TI  - Optimization of the PiggyBac transposon system for the sustained genetic
      modification of human T lymphocytes.
AB  - Optimal implementation of adoptive T-cell therapy for cancer will likely require
      multiple and maintained genetic modifications of the infused T cells and their
      progeny so that they home to tumor sites and recognize tumor cells, overcome
      tumor immune evasion strategies, and remain safe. Retroviral vectors readily
      transduce T cells and integrate into the host cell genome, but have a limited
      capacity for multigene insertion and cotransduction and are prohibitively
      expensive to produce at clinical grade. Genetic modification of T cells using
      transposons as integrating plasmids is an attractive alternative because of the
      increased simplicity and cost of production. Of available transposons, piggyBac
      has the higher transposase activity and larger cargo capacity, and we now
      evaluate piggyBac for potential adoptive therapies with primary T cells. PiggyBac
      transposons mediated stable gene expression in approximately 20% of primary T
      cells without selection. Treatment and maintenance of T cells with interleukin-15
      increased stable transgene expression up to approximately 40% and expression was
      sustained through multiple logs of expansion for over 9 weeks in culture. We
      demonstrate simultaneous integration of 2 independent transposons in 20% of T
      cells, a frequency that could be increased to over 85% by selection of a
      transgenic surface marker (truncated CD19). PiggyBac could also deliver
      transposons of up to 13 kb with 10,000-fold expansion of transduced T cells in
      culture and finally we demonstrate delivery of a functional suicide gene
      (iCasp9). PiggyBac transposons may thus be used to express the multiple
      integrated transgenes that will likely be necessary for the broader success of T
      cell therapy.

PMID- 19752752
TI  - Affitoxin--a novel recombinant, HER2-specific, anticancer agent for targeted
      therapy of HER2-positive tumors.
AB  - Expression of the human epidermal growth factor receptor 2 (HER2) is amplified in
      25% to 30% of breast cancers and has been associated with an unfavorable
      prognosis. Here we report the construction, purification, and characterization of
      Affitoxin-a novel class of HER2-specific cytotoxic molecules combining HER2
      specific Affibody molecule as a targeting moiety and PE38KDEL, which is a
      truncated version of Pseudomonas exotoxin A, as a cell killing agent. It is
      highly soluble and does not require additional refolding, oxidation, or reduction
      steps during its purification. Using surface plasmon resonance technology and
      competitive binding assays, we have shown that Affitoxin binds specifically to
      HER2 with nanomolar affinity. We have also observed a high correlation between
      HER2 expression and retention of Affitoxin bound to the cell surface. Affitoxin
      binding and internalization is followed by Pseudomonas exotoxin A activity domain
      mediated ADP-ribosylation of translation elongation factor 2 and, consequently,
      inhibition of protein synthesis as shown by protein expression analysis of HER2
      positive cells treated with Affitoxin. Measured IC50 value for HER2-negative
      cells MDA-MB468 (65+/-2.63 pM) was more than 20 times higher than the value for
      low HER2 level-expressing MCF7 cells (2.56+/-0.1 pM), and almost 3 orders of
      magnitude higher for its HER2-overexpressing derivative MCF7/HER2 (62.7+/-5.9
      fM). These studies suggest that Affitoxin is an attractive PE38-based candidate
      for treatment of HER2-positive tumors.

PMID- 19752753
TI  - IRF9 is a key factor for eliciting the antiproliferative activity of IFN-alpha.
AB  - A number of tumors are still resistant to the antiproliferative activity of human
      interferon (IFN)-alpha. The Janus kinases/Signal Transducers and Activators of
      Transcription (JAK-STAT) pathway plays an important role in initial IFN
      signaling. To enhance the antiproliferative activity of IFN-alpha, it is
      important to elucidate which factors in the JAK-STAT pathway play a key role in
      eliciting this activity. In human ovarian adenocarcinoma OVCAR3 cells sensitive
      to both IFN-alpha and IFN-gamma, only IFN regulatory factor 9 (IRF9)-RNA
      interference (RNAi) completely inhibited the antiproliferative activity of IFN
      alpha among the intracellular JAK-STAT pathway factors. Conversely, Stat1-RNAi
      did not inhibit the antiproliferative activity of IFN-alpha, whereas it partially
      inhibited that of IFN-gamma. As a cell death pathway, it is reported that tumor
      necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis
      through TRAIL-receptor (R) 1 and TRAIL-R2. In IFN-alpha-treated OVCAR3 cells,
      IRF9-RNAi inhibited transcription of TRAIL whereas Stat1-RNAi did not, suggesting
      that the transcription of TRAIL induced by IFN-alpha predominantly required IRF9.
      Furthermore, IFN-stimulated response element-like motifs of TRAIL bound to IFN
      stimulated gene factor 3 (ISGF3) complex after IFN-alpha treatment. Subsequently,
      TRAIL-R2-RNAi inhibited both antiproliferative activities of IFN-alpha and TRAIL,
      suggesting that TRAIL-R2 mediated both IFN-alpha and TRAIL signals to elicit
      their antiproliferative activities. Finally, IRF9 overexpression facilitated IFN
      alpha-induced apoptosis in T98G (human glioblastoma multiforme) cells, which were
      resistant to IFN-alpha. Thus, this study suggests that IRF9 is the key factor for
      eliciting the antiproliferative activity of IFN-alpha and TRAIL may be one of the
      potential mediators.

PMID- 19752755
TI  - Local AdCD40L gene therapy is effective for disseminated murine experimental
      cancer by breaking T-cell tolerance and inducing tumor cell growth inhibition.
AB  - CD40 ligand (CD40L) is one of the most potent stimulators of Th1-type immunity
      through its maturation of dendritic cells that, in turn, stimulate effector cells
      such as T cells and NK cells. Lately, CD40-mediated cell growth inhibition and
      apoptosis have been in focus for the development of novel cancer treatment
      regiments, including recombinant soluble CD40L or CD40-stimulating antibodies. In
      this study, intravesical CD40L gene transfer through adenoviral vectors (AdCD40L)
      was used to treat an aggressive model of disseminated bladder cancer
      (MB49/C57BL/6). Three weekly AdCD40L vector instillations increased overall
      survival of tumor-bearing mice (mean 18.5 d, control mice 13 d). Furthermore,
      bladder tumors were eradicated (2 of 10) simultaneously as lung metastases (6 of
      10) were cleared. FoxP3 levels were similar in the tumors of AdCD40L-treated mice
      and control mice but the tumor-infiltrating effector T cells in AdCD40L-treated
      mice were cytotoxic (CD107a+) in contrast to those in control-treated tumors.
      Furthermore, AdCD40L gene therapy could induce cell growth inhibition and cell
      death in the MB49 tumor cells in vitro and in vivo. However, this effect was not
      potent enough to cure growing tumors in immunodeficient mice. In conclusion,
      AdCD40L gene therapy is potent for disseminated cancer both by activation of T
      cells and controlling tumor cell growth and viability.

PMID- 19752754
TI  - IL-4 suppresses very late antigen-4 expression which is required for therapeutic
      Th1 T-cell trafficking into tumors.
AB  - Murine CD4 T cells cultured under type 1 polarizing conditions selectively
      express significantly higher levels of the very late antigen (VLA)-4 and VLA-6
      integrins when compared with T cells cultured under type 2 or nonpolarizing (type
      0) conditions. This difference appears due to the action of interleukin (IL)-4,
      as loss of VLA-4/-6 expression on Th cells was prevented by inclusion of
      neutralizing anti-IL-4 mAb during the initial culture period. We also observed
      that CD4 T cells deficient in Stat6, a critical component of the IL-4R signaling
      cascade, retained high levels of VLA-4 and VLA-6 expression, regardless of IL-4
      status in the culture conditions. When applied to committed Th1 cells, rIL-4
      readily inhibited VLA-4 and VLA-6 expression to levels observed for Th2 cells,
      without altering the type 1 functional status of these cells. Conversely, low
      levels of VLA-4/VLA-6 expressed by committed Th2 cells could not be resurrected
      by culture in the presence of the Th1-kines IL-12p70 and interferon-gamma.
      Predictably, among the Th populations evaluated, Th1 cells alone adhered
      efficiently to, and were costimulated by, plate-bound VCAM-1 and laminin in a VLA
      4-dependent or VLA-6-dependent manner, respectively. Finally, adoptive
      transferred Th1 (but not Th2) cells developed from OT-II mice were uniquely
      competent to traffick into OVA M05 melanoma lesions in vivo, thereby enhancing
      the therapeutic benefits associated with cotransferred OVA-specific type 1 CD8
      (OT-I) cells. These data suggest that treatment strategies capable of
      sustaining/enhancing VLA-4/VLA-6 expression on Th1 effector cells may yield
      improved clinical efficacy in the cancer setting.

PMID- 19752756
TI  - CD167 acts as a novel costimulatory receptor in T-cell activation.
AB  - Optimal T-cell activation requires both an antigen-specific and a costimulatory
      signal. CD167 is a tyrosine kinase receptor for native type I collagen, its
      physiologic functions include matrix homeostasis and cell growth, adhesion,
      branching, and migration, but the specific role of CD167 in T cells has not yet
      been characterized. In this study, we found that CD167 expression on T cells was
      up-regulated after activation. Cooperation of CD167 engagement with suboptimal
      TCR/CD3 signals induced T-cell proliferation, enhanced expression of activation
      markers such as CD25 and CD69, elevated intracellular calcium mobilization and
      tyrosine phosphorylation, and introduced a bias toward a TH1/Tc1 immune response.
      Cooperation of CD167 engagement also enhanced mixed lymphocyte responses to
      alloantigens. Moreover, CD167 rapidly localized to the aggregated lipid rafts
      upon T-cell activation, this provided a molecular base for the signaling
      machinery of CD167. Together these findings, we demonstrate for the first time
      that CD167 could serve as a novel costimulatory receptor for T-cell activation.

PMID- 19752757
TI  - Lung cancer diagnostic and treatment intervals in the United States: a health
      care disparity?
AB  - INTRODUCTION: Lung cancer diagnostic and treatment delays have been described for
      several patient populations. However, few studies have analyzed these intervals
      among patients treated in contemporary health care systems in the United States.
      We therefore studied the timing of lung cancer diagnosis and treatment at a U.S.
      medical center providing care to a diverse patient population within two
      different hospital systems. METHODS: We performed a retrospective analysis of
      consecutive patients diagnosed with non-small cell lung cancer stage I to III
      from 2000 to 2005 at public and private hospitals affiliated with the University
      of Texas Southwestern Medical Center. We recorded patient and disease
      characteristics; dates of initial radiograph suspicious for lung cancer,
      diagnosis, and treatment; and overall survival. Associations between these
      factors were assessed using univariate analysis, multivariate logistic
      regression, and Kaplan-Meier survival analysis. RESULTS: A total of 482 patients
      met criteria for analysis. In univariate analyses, the image-treatment interval
      was significantly associated with race, age, income, insurance type, and hospital
      type (76 days for public versus 45 days for private; p < 0.0001). In multivariate
      analysis, only hospital type remained significantly associated with the image
      treatment interval; patients in the private hospital setting were more likely to
      receive timely treatment (hazard ratio 1.85; 95% confidence interval, 1.37-2.50;
      p < 0.001). In univariate analysis, the image-treatment interval was not
      associated with disease stage (p = 0.27) or with survival (p = 0.42). CONCLUSION:
      Intervals between suspicion, diagnosis, and treatment of lung cancer vary widely
      among patients. Health care system factors, such as hospital type, largely
      account for these discrepancies. In this study, these intervals do not appear to
      be associated with clinical outcomes.

PMID- 19752758
TI  - Prognostic factors according to the treatment schedule in malignant pleural
      mesothelioma.
AB  - OBJECTIVES: In this study, we aimed to investigate the factors affecting the
      survival of patients with malignant pleural mesothelioma (MPM) according to their
      treatment schedules, including those treated with best supportive care,
      chemotherapy, and multimodality therapy. METHODS: We evaluated 235 patients with
      MPM. The patients were classified into three groups according to their treatment
      schedules: the best supportive care group, the chemotherapy group, and the
      multimodality therapy group. Prognostic factors were determined for all patients
      and for the three groups by univariate and multivariate analyses. However, the
      effectiveness of treatment schedules as a prognostic factor was not evaluated in
      this study. RESULTS: After adjusting for therapy in a Cox model, a Karnofsky
      Performance Status (KPS) < or = 70, a right side tumor, serum lactate
      dehydrogenase >500 IU(-1), a nonepithelial subtype, and stage 3 to 4 disease were
      determined by multivariate analyses to be unfavorable prognostic factors for all
      the patients. A KPS < or = 70, serum lactate dehydrogenase >500 IU(-1), a
      nonepithelial subtype, and stage 3 to 4 disease were associated with a poor
      prognosis for the best supportive care group. The single unfavorable prognostic
      factor for the chemotherapy group was a KPS < or = 70. A right side tumor and a
      nonepithelial subtype were associated with a poor prognosis for the multimodality
      therapy group. CONCLUSIONS: The patients with an epithelial subtype, a good KPS,
      and an early-stage tumor had a good prognosis, even if they did not receive any
      treatment. The only prognostic factor for the chemotherapy group was KPS. The
      histologic subtype and stage of the tumor were not related to the prognosis in
      this group. A mixed subtype and a right side tumor were unfavorable prognostic
      factors for the multimodality therapy group. These findings may be useful in
      counseling patients and in planning further studies.

PMID- 19752759
TI  - Improving survival for stage IV non-small cell lung cancer: a surveillance,
      epidemiology, and end results survey from 1990 to 2005.
AB  - BACKGROUND: Although there has been a significant survival improvement for
      patients with metastatic NSCLC enrolled in randomized trials, it is not clear
      whether a similar benefit is seen in an unselected group of patients. Therefore,
      we conducted a study to evaluate for survival changes in a large national cancer
      registry database. PATIENTS AND METHODS: The Surveillance, Epidemiology, and End
      Results (SEER) registry was queried for patients with NSCLC stage IV, aged 21
      years or older, and diagnosed between 1990 and 2005. We analyzed four equally
      divided time periods between 1990 and 2005 (1990 to 1993 or period 1, 1994 to
      1997 or period 2, 1998 to 2001 or period 3, and 2002 to 2005 or period 4) to
      determine changes in overall survival for all patients and according to
      histology. RESULTS: We identified 129,337 patients meeting eligibility criteria.
      There was a significant improvement in overall survival since period 1. One-year
      and 2-year overall survival increased from 13.2 and 4.5%, respectively, in period
      1 to 19.4% and 7.8%, respectively, in period 4. On multivariate analysis,
      survival for adenocarcinoma was increased compared with squamous cell carcinoma
      only in period 4 (p = 0.02). CONCLUSIONS: There has been a modest but
      statistically significant improvement in overall survival for stage IV NSCLC over
      the past 16 years. The recent differences in outcomes based on histology observed
      in period 4 may reflect the increased activity of epidermal growth factor
      receptor tyrosine kinase inhibitors in adenocarcinoma compared with squamous cell
      carcinoma.

PMID- 19752760
TI  - Clinical impact of endoscopic ultrasound-fine needle aspiration of left adrenal
      masses in established or suspected lung cancer.
AB  - INTRODUCTION: Correct lung cancer staging is pivotal for optimal allocation to
      surgical and nonsurgical treatment. A left adrenal gland (LAG) mass is found in 5
      to 16%, and malignancy preclude surgery. Endoscopic ultrasound (EUS) is superior
      to other imaging procedures in visualizing LAG, but the impact of EUS-fine needle
      aspiration (FNA) on tumor, node, metastasis (TNM)-staging, treatment, and
      survival is unknown. METHODS: The impact of EUS-FNA of the LAG on TNM staging,
      treatment, and survival was evaluated retrospectively in all patients (n = 40)
      referred to EUS during 2000-2006 for known or suspected lung cancer and where EUS
      disclosed an enlarged LAG. Conventional workup had preceded EUS. RESULTS: EUS-FNA
      of an enlarged LAG altered the TNM staging in 70% (downstaged: 26 of 28 patients)
      and treatment in 48% (gained surgery 25%, avoided surgery 5%, surgically verified
      benign disease 5%, no cancer and no further workup 5%, and no cancer, control
      computed tomography, and then no further workup 8%). A malignant LAG lesion was
      found in 28% and was significantly associated with shorter survival. CONCLUSION:
      EUS-FNA of an enlarged LAG in patients with known or suspected lung cancer had a
      significant impact on TNM staging, treatment, and survival. The impact of routine
      visualization of the LAG in lung cancer workup needs to be prospectively
      validated.

PMID- 19752761
TI  - Submaximal exercise coronary artery flow increases in postmenopausal women
      without coronary artery disease after estrogen and atorvastatin.
AB  - OBJECTIVE: The aim of this study was to determine the effect of statins and
      hormone therapy on submaximal exercise-induced coronary artery blood flow in
      postmenopausal women without a history of coronary artery disease. Hormone
      therapy or statin therapy in early postmenopausal women without coronary artery
      disease has been shown to enhance arterial endothelial function; we hypothesized
      that these agents would improve submaximal exercise-induced coronary artery blood
      flow. METHODS: Sixty-four postmenopausal women, aged 50 to 65 years without
      documented coronary artery disease, were randomized in a double-blind, crossover
      fashion to receive 8 weeks of hormone therapy versus placebo, with or without 80
      mg/day of atorvastatin. Before receipt of any therapy and after each treatment
      period, each woman underwent measures of coronary artery blood flow at rest and
      stress. RESULTS: The combination of hormone therapy and atorvastatin increased
      submaximal exercise-induced coronary artery blood flow (P = 0.04). In the
      subgroups of women compliant with treatment, resting coronary artery blood flow
      increased in those receiving hormone therapy (P = 0.03) or statin therapy (P =
      0.02). CONCLUSIONS: In postmenopausal women aged 50 to 65 years without
      documented coronary artery disease, resting and submaximal exercise-induced
      coronary artery blood flow improves after receipt of high-dose atorvastatin and
      conjugated estrogens therapy.

PMID- 19752762
TI  - Is antral follicle count a genetic trait?
AB  - OBJECTIVE: The aim of this study was to determine the relationship between
      maternal age of menopause and antral follicle count. METHODS: This was a cross
      sectional study of 124 women aged 25 to 48 years presenting with infertility.
      Women reported their mother's age of menopause and underwent transvaginal
      ultrasound to assess antral follicle count. Participant age, age greater than 37
      years, and maternal age of menopause, as well as interactions among these, were
      incorporated into a multiple linear regression model to predict antral follicle
      count. Three different ages of maternal menopause were inputted into this model
      to illustrate the relationship between maternal age of menopause and rate of
      decline in antral follicle count. RESULTS: Women with a lower maternal age of
      menopause have lower antral follicle counts but also a slower decline until the
      age of 37 years. CONCLUSIONS: Maternal age of menopause predicts antral follicle
      count and its decline, indicating a genetic component to this trait.

PMID- 19752763
TI  - Hippocampal Fyn activity regulates extinction of contextual fear.
AB  - Contextual fear memory is attenuated by reexposure of animals to a context alone
      without pairing it with an unconditioned stimulus, a phenomenon referred to as
      fear extinction. Here, we report that Fyn tyrosine kinase in the hippocampus is
      involved in the extinction of contextual fear. We inhibited Src-family tyrosine
      kinases in the dorsal hippocampus by stereotaxic injection of an inhibitor, PP2,
      and observed facilitation of extinction. We then biochemically analyzed dorsal
      hippocampal tissue during extinction training, and found that activated Fyn was
      significantly downregulated among the Src-family tyrosine kinases examined. These
      findings suggest that downregulation of Fyn activity facilitates the extinction
      of contextual fear.

PMID- 19752764
TI  - Mutant SOD1 G93A microglia have an inflammatory phenotype and elevated production
      of MCP-1.
AB  - The inflammatory response in amyotrophic lateral sclerosis (ALS) is well
      documented but the underlying cellular mechanisms have not been fully elucidated.
      We report that microglia isolated from the mutant human superoxide dismutase 1
      (SOD1) G93A transgenic mouse model of ALS have an increased response to the
      inflammatory stimulus, lipopolysaccharide. Cell surface area and F4/80 surface
      marker, both indicators of cell activation, are increased relative to transgenic
      wild-type human SOD1 microglia. Monocyte chemoattractant protein-1, known to be
      increased in ALS, is produced at three-fold higher levels by SOD1 G93A than by
      wild-type human SOD1 microglia, under activating conditions. This novel finding
      implicates ALS microglia as a source of the increased monocyte chemoattractant
      protein-1 levels detected in ALS patients and in the ALS mouse model.

PMID- 19752765
TI  - Indication for surgery in otosclerotic patients with unilateral hearing loss.
AB  - OBJECTIVE: The aim of this study is to evaluate postoperative spatial speech
      discrimination in noise in a group of otosclerotic patients with unilateral
      hearing loss in a 6-month follow-up. Moreover, an additional objective is to
      verify if our routine criteria (air-bone gap >30 dB at 250-2,000 Hz) for surgical
      indication in such patients can be acceptable. STUDY DESIGN: Prospective
      evaluation in 20 patients divided into 2 groups: unilateral otosclerosis and
      bilateral otosclerosis already successfully operated on 1 side and planned for
      stapedotomy on the contralateral ear. SETTING: Tertiary referral center,
      University clinic. PATIENTS: Otosclerotic patients with unilateral hearing loss.
      INTERVENTION: Evaluation of functional outcome. MAIN OUTCOME MEASURE: Spatial
      test based on speech discrimination in noise. RESULTS: All patients reach
      postoperative air-bone gap closure within 10 dB. Average postoperative gain in
      discrimination under noise was 11.5% for unilateral otosclerosis group and 19.3%
      for the second ear group. CONCLUSION: Free-field discrimination in noise closely
      reflects the usual listening conditions in everyday life. Improvement in
      postoperative free-field discrimination in noise can justify our routine criteria
      for surgical indication in the patients with unilateral otosclerosis and with
      bilateral otosclerosis already operated on 1 side. The surgical choice for each
      patient, apart from audiologic evaluation, is linked to a truly informed consent
      regarding possible advantages and risks mainly based on an analysis of the real
      auditory needs of the patient and individual results of the surgeon.

PMID- 19752766
TI  - Revision stapedectomy: an analysis of 201 operations.
AB  - INTRODUCTION: Recurrent or persistent conductive hearing impairment as well as
      vertigo or tinnitus after a stapes operation can be treated by means of stapes
      revision surgery. We analyzed stapes revisions performed during the last 15 years
      at our institution. The aim was to ascertain the causes that led to the failure,
      to analyze the postrevision results, and to compare them with data from the
      literature. MATERIALS AND METHODS: This retrospective study analyzes 201 stapes
      revisions performed in 175 patients between 1992 and 2006. The indications,
      intraoperative findings, and surgical techniques were analyzed. Functional
      results were evaluated by means of hearing tests before and after surgery (1-15
      yr). Revisions were mainly performed by the transcanal approach through the fixed
      speculum under local anesthesia using the fiber-optic argon laser and the Skeeter
      microdrill. RESULTS: Indications for revision in 172 operations included lack of
      hearing improvement or recurrent conductive hearing loss. Six patients
      additionally had symptoms of vertigo. Sixteen patients experienced isolated
      vertigo despite improved hearing, 1 patient experienced intolerable tinnitus, and
      in 6 patients, the indication was deafness after stapedotomy.The most common
      intraoperative observations were prosthesis lateralization (53%), partial or
      total incus necrosis (33%), reossification of the footplate (31%), and loosening
      of the loop on the incus (9%). Hearing improved postoperatively in 88% of the
      patients. In 55% of the patients, there was a residual air-bone gap of 10 dB or
      less, and in 84%, the gap was 20 dB or less. DISCUSSION: Stapes revisions are
      more challenging procedures with less perfect results compared with primary
      operations. Nevertheless, a postoperative hearing improvement was achieved in 88%
      of our patients. Modern techniques, such as the laser and microdrill, demonstrate
      their full usefulness.

PMID- 19752767
TI  - Reconstitution of the mast cell population in W/Wv mice.
AB  - HYPOTHESIS: Intravenous injection of cultured mast cells (MCs) can reconstitute
      the MC population in MC-deficient mice. We hypothesize that injected culture
      derived MCs do not repopulate all tissues equally. BACKGROUND: Mast cells are
      central elements not only in anaphylaxis and allergy but also in immune reactions
      to bacteria and other pathogens. Their broad involvement in innate immunity
      requires extensive research in the future. Studies of MC function often use MC
      deficient mice to compare with wild-type animals. A very elegant method to prove
      that the observed changes are due to the lack of MCs is to compare results in
      wild-type mice, MC-deficient mice, and MC-deficient mice that have been
      reconstituted with cultured MCs. Reconstitution of the MC population can be
      achieved by intravenous injection of MCs into MC-deficient mice. Whether the
      injected MCs repopulate the desired tissues has to be proven before this model is
      used. Also, the time frame of the reconstitution has to be demonstrated. METHODS:
      Mast cell-deficient mice were injected with bone marrow-derived cultured MCs, and
      the mucosa of middle ear (MEs), nose, and tracheobronchial system was analyzed
      for MCs 4, 6, 8, 10, and 20 weeks after injection. RESULTS: Reconstitution of the
      ME mucosa was complete and persistent for more than 20 weeks. Reconstitution
      failed in nasal mucosa. In bronchial mucosa, reconstitution was incomplete and
      transient. CONCLUSION: This model can be used to investigate effects of MCs in
      various immune reactions in the ME. Studies should use the time frame 6 to 8
      weeks after reconstitution of the MC population. However, the model has
      limitations for investigations in the respiratory tract.

PMID- 19752768
TI  - Cyst size indicates malignant transformation in branch duct intraductal papillary
      mucinous neoplasm of the pancreas without mural nodules.
AB  - OBJECTIVES: In branch duct intraductal papillary mucinous neoplasm (IPMN) of the
      pancreas, the importance of the cyst size to predict malignancy is still
      controversial. Our aim was to elucidate the malignant potential of branch duct
      IPMN without mural nodules (flat branch duct IPMN). METHODS: Seventy-three
      patients with flat branch duct IPMNs were studied in our institution. RESULTS:
      There were 6 malignant IPMNs in this series, all of which were 30 mm or more in
      size, whereas there was no malignancy in IPMNs of less than 30 mm. Statistically
      significant predictors of malignancy were atypical cytological condition and main
      pancreatic duct (MPD) diameter of 5 mm or more. The cyst size of 30 mm or more
      tended to be associated with malignancy. The frequency of malignancy in flat
      branch duct IPMNs with the size of 30 mm or more and MPD diameter of less than 5
      mm was 3.6%, whereas there were 5 malignant cases (26.3%) in flat branch duct
      IPMNs with the size of 30 mm or more and MPD diameter of 5 mm or more.
      CONCLUSIONS: We conclude that the size criteria (> or =30 mm) to predict
      malignancy proposed in the international consensus guidelines is appropriate and
      resection or meticulous follow-up using cytological examination and MPD
      dilatation is needed in patients with flat branch duct IPMNs.

PMID- 19752769
TI  - Combination of hemofiltration and peritoneal dialysis in the treatment of severe
      acute pancreatitis.
AB  - OBJECTIVE: Our aim was to study the therapeutic effects and the mechanism of
      combination of hemofiltration (HF) and peritoneal dialysis (PD) in the treatment
      of severe acute pancreatitis (SAP). METHODS: Fifty-one cases of SAP were randomly
      divided into the HF+PD group (treated group, 36 patients) and the non-HF+PD group
      (control group, 15 patients). Both groups were treated by the same traditional
      methods. The relief time of abdominal pain and abdominal distension, computed
      tomographic scores, acute physiology and chronic health enquiry II scores, length
      of stay, cost of hospitalization, operability, and recovery rate of the 2 groups
      were compared. The concentration of tumor necrosis factor-alpha, IL-6, and IL-8
      in serum and ascites volumes was determined before and after treatment. RESULTS:
      : The mean time of abdominal pain relief, amelioration of abdominal distension,
      decrease of computed tomographic scores, acute physiology and chronic health
      enquiry II scores, the mean length of stay, and cost of hospitalization of the
      treated group were significantly shorter or less than those of the control group.
      The aforementioned inflammatory cytokines, detected at the end of 1 day and 2
      days after HF+PD treatment, were decreased significantly compared with those
      observed in pretherapy and the control group. CONCLUSIONS: Inflammatory
      cytokines, which overproduced in SAP, can be eliminated effectively from the
      blood and the ascites by HF+PD treatment.

PMID- 19752770
TI  - Increasing incidence of acute pancreatitis at an American pediatric tertiary care
      center: is greater awareness among physicians responsible?
AB  - OBJECTIVES: Studies show an increased incidence of adult acute pancreatitis (AP)
      in recent decades. The aim was to review pediatric AP incidence. METHODS:
      Retrospective review of computerized databases at the Children's Hospital of
      Pittsburgh from 1993 to 2004. The International Classification of Diseases, Ninth
      Revision, code 5770 Acute Pancreatitis was used; results were tabulated by
      discharge year and month. The incidence of AP was compared with orders for
      amylase and lipase testings and with the catchment population. RESULTS: Over the
      study period, there were a total of 1021 discharge diagnoses of AP (731 first
      diagnoses). The diagnosis of AP increased from a low of 28 total cases (21 first
      diagnoses) in 1993 to a high of 141 total cases (109 first diagnoses) in 2004.
      The catchment population decreased from 882,000 to 826,500. The estimated
      incidences of first AP admission were 2.4 to 13.2 per 100,000 children (years
      1993-2004; r = 0.8339). Linear regression analysis suggests that increased
      testing for amylase and lipase could account for 94% of the change in all AP
      admissions (P = 5.1 x 10). CONCLUSIONS: The increased incidence of AP at the
      Children's Hospital of Pittsburgh from 1993 to 2004 may have been primarily
      driven by increased testing for the disease.

PMID- 19752771
TI  - Urinary trypsinogen-2 dipstick in acute pancreatitis.
AB  - OBJECTIVES: In acute pancreatitis (AP), rapid diagnosis and early treatment are
      of importance for clinical outcome. Urinary trypsinogen-2 has been suggested as a
      promising diagnostic marker; however, studies using the urinary trypsinogen-2
      dipstick test (UTDT) have provided varying results. METHODS: The study was set to
      evaluate the use of the UTDT (Actim Pancreatitis; Medix Biochemica, Kauniainen,
      Finland, Medinor, Roskilde, Denmark) in apparent first attack of AP in daily
      clinics. Acute pancreatitis was defined as more than a 3-fold increase in plasma
      amylase levels. We included 75 patients admitted with AP. Thirty-four patients
      with acute abdominal pain of causes other than AP served as a control group.
      RESULTS: In 58 of 75 patients, the UTDT result was positive, giving a sensitivity
      of 77% (95% confidence interval [CI]: 66%-86%). In severe cases, the sensitivity
      improved to 87% (95% CI: 69%-96%). In 33 of 34 controls, the test result was
      negative, giving a specificity of 97% (95% CI: 84%-99.9%). CONCLUSION: The UTDT
      had a low sensitivity but high specificity. These results do not support the UTDT
      to replace standard plasma amylase for the diagnosis of apparent first attack of
      AP. However, the test demonstrated an adequate sensitivity to be used for rapid
      early screening of AP in daily clinics.

PMID- 19752772
TI  - MDM2 SNP309 associates with accelerated pancreatic adenocarcinoma formation.
AB  - OBJECTIVES: The G-allele of a single nucleotide polymorphism in the promoter of
      the MDM2 gene (MDM2 SNP309, T/G) associates with the acceleration of tumor
      formation and an increased risk for developing various malignancies. In this
      report, the possible role of the MDM2 SNP309 locus with regard to sex, age, and
      p53 mutational status in the development and progression of pancreatic ductal
      adenocarcinoma (PDAC) was examined. METHODS: One hundred three PDAC patients with
      comprehensive clinical, histopathologic, and follow-up data and 499 controls were
      included into the study and their MDM2 SNP309 genotypes obtained. RESULTS:
      Interestingly, the G-allele of MDM2 SNP309 is shown to associate with a 9-year
      earlier age of PDAC onset (P = 0.021). However, in contrast to studies of other
      tumor types, these observations are made predominantly in men and not women.
      Conditions of male PDAC patients with a G/G genotype are diagnosed at a mean of
      12 years earlier than T-allele carriers (P = 0.0032). Furthermore, particularly
      younger male patients present a significant enrichment of the G-allele (P =
      0.019). CONCLUSIONS: These observations suggest a novel role of the MDM2 SNP309
      locus in regulating PDAC tumor formation in a male-specific manner.

PMID- 19752773
TI  - Protein kinase C delta-mediated processes in cholecystokinin-8-stimulated
      pancreatic acini.
AB  - OBJECTIVES: To define the role of protein kinase C delta (PKC delta) in acinar
      cell responses to the hormone cholecystokinin-8 (CCK) using isoform-specific
      inhibitors and a previously unreported genetic deletion model. METHODS:
      Pancreatic acinar cells were isolated from (1) rat, and pretreated with a PKC
      delta-specific inhibitor or (2) PKC delta-deficient and wild type mice. Isolated
      cells were stimulated with CCK (0.001-100 nmol/L) and cell responses were
      measured. RESULTS: The PKC delta inhibitor did not affect stimulated amylase
      secretion from rat pancreatic acinar cells. Cholecystokinin-8 stimulation induced
      a typical biphasic dose-response curve for amylase secretion in acinar cells
      isolated from both PKC delta(-/-) and wild type mice, with maximal stimulation at
      10-pmol/L CCK. Cholecystokinin-8 (100 nmol/L) induced zymogen and nuclear factor
      kappaB activation in both PKC delta(-/-) and wild type mice, although it was up
      to 50% less in PKC delta(-/-). CONCLUSIONS: In contrast to previous studies, this
      study has used specific and complementary approaches to examine PKC delta
      mediated acinar cell responses. We could not confirm that it mediates amylase
      release but corroborated its role in the early stages of acute pancreatitis.

PMID- 19752774
TI  - CFTR expression but not Cl- transport is involved in the stimulatory effect of
      bile acids on apical Cl-/HCO3- exchange activity in human pancreatic duct cells.
AB  - OBJECTIVES: Low doses of chenodeoxycholate (CDC) stimulate apical anion exchange
      and HCO3(-) secretion in guinea pig pancreatic duct cells (Gut. 2008;57:1102
      1112). We examined the effects of CDC on intracellular pH (pHi), intracellular
      Ca(2+) concentration ([Ca(2+)]i), and apical Cl(-)/HCO3(-) exchange activity in
      human pancreatic duct cells and determined whether any effects were dependent on
      cystic fibrosis transmembrane conductance regulator (CFTR) expression and Cl(-)
      channel activity. METHODS: Polarized CFPAC-1 cells (expressing F508del CFTR) were
      transduced with Sendai virus constructs containing complementary DNAs for either
      wild-type CFTR or beta-galactosidase. Microfluorimetry was used to record pHi and
      [Ca(2+)]i and apical Cl(-)/HCO3(-) exchange activity. Patch clamp experiments
      were performed on isolated guinea pig duct cells. RESULTS: Chenodeoxycholate
      induced a dose-dependent intracellular acidification and a marked increase in
      [Ca(2+)]i in CFPAC-1 cells. CFTR expression slightly reduced the rate of
      acidification but did not affect the [Ca(2+)]i changes. Luminal administration of
      0.1 mmol/L of CDC significantly elevated apical Cl(-)/HCO3(-) exchange activity
      but only in cells that expressed CFTR. However, CDC did not activate CFTR Cl(-)
      conductance. CONCLUSIONS: Bile salts modulate pHi, [Ca(2+)]i, and apical anion
      exchange activity in human pancreatic duct cells. The stimulatory effect of CDC
      on anion exchangers requires CFTR expression but not CFTR channel activity.

PMID- 19752775
TI  - Frequent and significant K-ras mutation in the pancreas, the bile duct, and the
      gallbladder in autoimmune pancreatitis.
AB  - OBJECTIVES: To assess the relationship between autoimmune pancreatitis (AIP) and
      pancreatic cancer, we analyzed K-ras mutation in the pancreatobiliary tissues of
      patients with AIP. METHODS: An analysis of K-ras mutation and an
      immunohistochemical study were performed on the pancreas of 8 patients with AIP
      and 10 patients with chronic alcoholic pancreatitis and on the common bile duct
      and the gallbladder of 9 patients with AIP. K-ras mutation was analyzed in the
      pure pancreatic juice from 3 patients with AIP. RESULTS: High-frequency K-ras
      mutation (2+ or 3+) was detected in the pancreas of all the 8 patients and in the
      pancreatic juice of the other 2 patients. The mutation in codon 12 of the ras
      gene was GAT in all the 10 patients. High-frequency K-ras mutation was detected
      in the common bile duct of 5 patients with AIP and in the gallbladder epithelium
      of 4 patients with AIP. The K-ras mutation was detected in the fibroinflammatory
      pancreas, the bile duct, and the gallbladder, with abundant infiltrating IgG4
      positive plasma and Foxp3-positive cells of patients with AIP with elevated serum
      IgG4 levels. CONCLUSIONS: Significant K-ras mutation occurs most frequently in
      the pancreatobiliary regions of patients with AIP. Autoimmune pancreatitis may be
      a risk factor of pancreatobiliary cancer.

PMID- 19752776
TI  - Noninvasive positive-pressure ventilation avoids recannulation and facilitates
      early weaning from tracheotomy in children.
AB  - OBJECTIVE: To show that noninvasive positive-pressure ventilation by means of a
      nasal mask may avoid recannulation after decannulation and facilitate early
      decannulation. DESIGN: Retrospective cohort study. SETTING: Ear-nose-and-throat
      and pulmonary department of a pediatric university hospital. PATIENTS: The data
      from 15 patients (age = 2-12 yrs) who needed a tracheotomy for upper airway
      obstruction (n = 13), congenital diaphragmatic hypoplasia (n = 1), or lung
      disease (n = 1) were analyzed. Four patients received also nocturnal invasive
      ventilatory support for associated lung disease (n = 3) or congenital
      diaphragmatic hypoplasia (n = 1). Decannulation was proposed in all patients
      because endoscopic evaluation showed sufficient upper airway patency and normal
      nocturnal gas exchange with a small size closed tracheal tube, but obstructive
      airway symptoms occurred either immediately or with delay after decannulation
      without noninvasive positive-pressure ventilation. INTERVENTIONS: In nine
      patients, noninvasive positive-pressure ventilation was started after recurrence
      of obstructive symptoms after a delay of 1 to 48 mos after a successful immediate
      decannulation. Noninvasive positive-pressure ventilation was anticipated in six
      patients who failed repeated decannulation trials because of poor clinical
      tolerance of tracheal tube removal or tube closure during sleep. MEASUREMENTS AND
      MAIN RESULTS: After noninvasive positive-pressure ventilation acclimatization,
      decannulation was performed with success in all patients. Noninvasive positive
      pressure ventilation was associated with an improvement in nocturnal gas exchange
      and marked clinical improvement in their obstructive sleep apnea symptoms. None
      of the 15 patients needed tracheal recannulation. Noninvasive positive-pressure
      ventilation could be withdrawn in six patients after 2 yrs to 8.5 yrs. The other
      nine patients still receive noninvasive positive-pressure ventilation after 1 yr
      to 6 yrs. CONCLUSIONS: In selected patients with upper airway obstruction or lung
      disease, noninvasive positive-pressure ventilation may represent a valuable tool
      to treat the recurrence of obstructive symptoms after decannulation and may
      facilitate early weaning from tracheotomy in children who failed repeated
      decannulation trials.

PMID- 19752777
TI  - Genetic and environmental factors determining clinical outcomes and cost of
      warfarin therapy: a prospective study.
AB  - BACKGROUND: In this prospective cohort study, we have undertaken a comprehensive
      evaluation of clinical parameters along with variation in 29 genes (including
      CYP2C9 and VKORC1) to identify factors determining interindividual variability in
      warfarin response. METHODS: Consecutive patients (n=311) were followed up
      prospectively for 26 weeks. Several outcomes chosen to capture both warfarin
      efficacy and toxicity were assessed. Univariate and multiple regression analyses
      were undertaken to assess the combined effect of clinical and genetic factors.
      RESULTS: CYP2C9 was the most important gene determining initial anticoagulant
      control, whereas VKORC1 was more important for stable anticoagulation. Novel
      associations with some clinical outcomes were found with single nucleotide
      polymorphisms in the cytochrome 450 genes CYP2C18 and CYP2C19, which were
      independent of the associations observed with CYP2C9 and in genes encoding
      CYP3A5, protein S and clotting factor V, although the variability explained by
      these genes was small. On the basis of the results of microcosting, adverse
      events were shown to be a significant predictor of total cost. CONCLUSION:
      Accurate prediction of warfarin dose requirement needs to take into account
      multiple genetic and environmental factors, the contributions of which vary in
      the induction and maintenance phases of treatment.

PMID- 19752778
TI  - Consequences of the Y139F Vkorc1 mutation on resistance to AVKs: in-vivo
      investigation in a 7th generation of congenic Y139F strain of rats.
AB  - OBJECTIVES: In humans, warfarin is used as an anticoagulant to reduce the risk of
      thromboembolic clinical events. Warfarin derivatives are also used as
      rodenticides in pest control. The gene encoding the protein targeted by
      anticoagulants is the Vitamin K-2,3-epoxide reductase subunit 1 (VKORC1). Since
      its discovery in 2004, various amino acid and transcription-regulatory altering
      VKORC1 mutations have been identified in patients who required extreme
      antivitamin K dosages, or wild populations of rodents that were difficult to
      control with anticoagulant rodenticides. One unresolved question concerns the
      dependency of the VKORC1 on the genetic background in humans and rodents that
      respond weakly or not at all to anticoagulants. Moreover, an important question
      requiring further analyses concerns the role of the Vkorc1 gene in mediating
      resistance to more recently developed warfarin derivatives (superwarfarins).
      METHODS: In this study, we bred a quasicongenic rat strain by using a wild-caught
      anticoagulant resistant rat as a donor to introduce the Y>F amino acid change at
      position 139 in the Vkorc1 into the genetic background of an anticoagulant
      susceptible Spraque-Dawley recipient strain. RESULTS AND CONCLUSION: In this
      manuscript we report the prothrombin times measured in the F7 generation after
      exposure to chlorophacinone, bromadiolone, difenacoum and difethialone. We
      observed that the mutation Y139F mediates resistance in an otherwise susceptible
      genetic background when exposed to chlorophacinone and bromadiolone. However, the
      physiological response to the super-warfarins, difenacoum and difethialone, may
      be strongly dependent on other genes located outside the congenic interval (28.3
      cM) bracketing the Vkorc1 in our F7 generation congenic strain.

PMID- 19752780
TI  - [Stroke task force: what are the stakes for radiology?].

PMID- 19752781
TI  - [The Second World War].

PMID- 19752779
TI  - Sphinganine-1-phosphate attenuates both hepatic and renal injury induced by
      hepatic ischemia and reperfusion in mice.
AB  - Hepatic ischemia/reperfusion (I/R) injury is a major complication after liver
      transplantation, major hepatic resection, or prolonged portal vein occlusion.
      Furthermore, acute kidney injury is frequent after hepatic I/R and greatly
      increases postoperative complications. Sphinganine-1-phosphate is a sphingolipid
      with uncharacterized physiological effects. We serendipitously determined that
      plasma levels of sphinganine-1-phosphate fell significantly after liver I/R in
      mice. In this study, we hypothesized that repletion of plasma sphinganine-1
      phosphate would protect against liver and kidney injuries after liver I/R.
      C57BL/6 mice were subjected to 60 min of partial hepatic I/R and treated with
      either vehicle or with sphinganine-1-phosphate (given immediately before and 2 h
      after reperfusion). Vehicle-treated mice subjected to liver I/R developed acute
      liver and kidney injuries with elevated plasma alanine aminotransferase and
      creatinine 5 and 24 h after liver I/R. However, liver and kidney injuries were
      significantly attenuated with sphinganine-1-phosphate treatment. Sphinganine-1
      phosphate markedly inhibited liver and kidney necrosis and apoptosis 24 h after
      liver I/R. Moreover, sphinganine-1-phosphate attenuated neutrophil infiltration,
      reduced plasma IL-6 and TNF-alpha upregulation, and preserved liver and kidney
      vascular integrity while reducing liver and kidney F-actin degradation after
      liver I/R. Finally, sphinganine-1-phosphate-mediated hepatic and renal protection
      was blocked by VPC23019, an antagonist for sphingosine-1-phosphate type 1
      receptor. Therefore, sphinganine-1-phosphate improves acute liver and kidney
      injuries after hepatic I/R via sphingosine-1-phosphate type 1 receptor-mediated
      inhibition of necrosis and apoptosis and by improving vascular integrity.
      Harnessing the mechanisms of cytoprotection with sphinganine-1-phosphate
      activation may lead to new therapies for perioperative hepatic I/R injury and
      subsequent remote organ injury.

PMID- 19752782
TI  - [The Journal of Radiology 1939-45].

PMID- 19752783
TI  - [Diagnostic accuracy of 64 row multidetector computed tomography for coronary
      artery disease assessment].
AB  - Due to technical advances, multidetector computed tomography (MDCT) allows
      evaluation of the coronary arteries and could in specific clinical indications
      provide a minimally invasive alternative to coronary angiography (CA). Recent
      technical advances combined with the availability of 64 row MDCT have
      significantly improved the evaluation of the native coronary arteries. However
      limitations remain for the evaluation of bypass grafts and stents. In this paper,
      we present a review the current literature on the diagnostic accuracy of 64 row
      MDCT in the assessment of coronary artery disease, and discuss the clinical
      implications and proposed indications of coronary CTA.

PMID- 19752784
TI  - [MR Imaging of primary ovarian tumors with pathologic correlation].
AB  - Ovarian tumors are classified based on the cell of origin into epithelial tumors,
      germ cell tumors and sex cord-stromal tumors. This pictorial essay illustrates
      the MR imaging features of the main ovarian tumors with pathologic correlation.
      These key features are helpful to suggest a specific diagnosis or narrow the
      differential diagnosis, in order to optimize the surgical approach.

PMID- 19752785
TI  - [Stent-graft treatment of the descending thoracic aorta in high risk patients].
AB  - PURPOSE: To report our experience with endovascular stent-graft repair of
      descending thoracic aorta diseases in high risk patients. MATERIALS AND METHODS:
      Between 2000 and 2007, 49 high surgical risk patients (mean age: 64.6 years)
      underwent stent-graft placement, including 24 cases presenting acutely. Mean
      follow-up was 25.4 months. Etiologies included 15 aneurysms, 11 dissections, 10
      penetrating ulcers, 9 false aneurysms, 2 ruptures of the aortic isthmus, 2
      intramural hematomas. RESULTS: Access failure occurred in one patient. The
      overall mortality was 27.1% (n=13), nine related to the presenting pathology or
      treatment. Thirty-day mortality was 10.4% (n=5). Complications included vascular
      injury at the iliac or femoral artery access (10.2%), 1 case of flaccid
      paraplegia, 2 cases of transient paraparesis, 2 strokes, 2 stent migrations and 1
      stent rupture. The rate of early endoleak was 39.6% while the rate of delayed
      endoleak was 14.6%. Seven patients (14.6%) required repeat endovascular
      interventions. Explantation was required in 2 cases. The latest available follow
      up showed no lesion enlargement in 70.7% (n=29/41) of our patients. CONCLUSION:
      Descending thoracic aortic pathology can be treated using endografts in high risk
      patients, although significant morbidity and mortality remain. Because of the
      high rate of endoleaks, close follow-up is required.

PMID- 19752786
TI  - [High resolution sonography of the dorsal radiocarpal and intercarpal ligaments:
      findings in healthy subjects with anatomic correlation to cadaveric wrists].
AB  - PURPOSE: To assess the value of ultrasound (US) imaging of the dorsal radiocarpal
      and intercarpal ligaments of the wrist, after characterization of their imaging
      features on cadaveric specimen. MATERIALS AND METHODS: Two wrist dissections of
      fresh cadaver were performed. The orientations and the osseous insertions of the
      ligaments were clarified, allowing development of an US examination protocol.
      Then, forty wrists of asymptomatic volunteers were analyzed prospectively with
      US. The visibility and thickness of both ligaments were estimated at their
      midpoint and at their osseous insertions. RESULTS: The dorsal radiocarpal and
      intercarpal ligaments were visualized as thin, hyperechoic and fibrillar
      structures, extending between their respective osseous insertions. The mid
      portions of the ligaments were visible at all volunteers. The osseous insertions
      were completely or partially visible in 90% of cases, except for the radial
      insertion of the dorsal radiocarpal ligament, visible in 77.5% of cases.
      CONCLUSION: US, based on good anatomical knowledge and a standardized protocol,
      which we describe in this work, enables evaluation of the dorsal radiocarpal and
      intercarpal ligaments of the wrist.

PMID- 19752787
TI  - [Anatomy of the female pelvis on MRI: value of intravaginal contrast].
AB  - PURPOSE: Prospective monocentric study to determine the feasibility, tolerability
      and diagnostic value of intravaginal contrast to assess female pelvic anatomy on
      MRI. MATERIALS AND METHODS: Forty-nine consecutive women referred for MRI
      evaluation of the pelvis, irrespective of the indication, were included in this
      study. The MR imaging protocol consisted of axial and sagittal T2W images before
      and after intravaginal instillation of sterile US gel. Eight anatomical regions
      were analyzed and their visibility graded from 1 to 4 (1=excellent; 4=non
      visualized) by 3 radiologists without and with intravaginal gel. The value of
      intravaginal gel was determined by calculating the difference in the visibility
      index for each anatomical region by the Wilcoxon and khi2 tests. Inter-observer
      agreement was also determined using the kappa test. RESULTS: Two women declined
      vaginal opacification resulting in an acceptance rate of 96%. The gel
      instillation procedure had a duration of less than 3 minutes on average and was
      well tolerated by all patients. Intravaginal gel allowed significantly improved
      visualization of all anatomical regions (p<0.001); improvement between 0.5 and
      2.5 points on average per anatomical region. Inter-observer agreement
      significantly improved after gel instillation increasing from 72% to 92%.
      CONCLUSION: Intravaginal instillation of US gel is simple, noninvasive, well
      accepted and well-tolerated by patients. It increases visibility of pelvic
      anatomical structures with improved inter-observer agreement.

PMID- 19752788
TI  - [ECG-gated chest CT angiography: value for atypical chest pain evaluation].
AB  - PURPOSE: The aim of this study was to evaluate ECG-gated whole chest CTA as a
      routine triage tool for patients with acute chest pain. MATERIAL AND METHODS:
      Whole chest CTA with retrospective ECG-gating was performed in 30 patients with
      acute atypical chest pain. The ten main segments of the coronary arteries, the
      pulmonary arteries, the aorta, and the myocardium (function, morphology) were
      independently analyzed by a resident and two senior radiologists. The inter
      observer agreement between resident and senior radiologists was calculated. A
      final diagnosis was determined by consensus. RESULTS: Thirty patients were
      included. The coronary artery segments, myocardium and pulmonary arteries were
      considered analyzable in 84%, 90% and 97% of cases respectively. A final
      diagnosis for the cause of pain was retained in 19 patients: significant coronary
      artery stenosis (5), pulmonary embolus (5), aortic dissection (1), hypokinetic
      cardiomyopathy (2), lung parenchymal abnormalities (5), and hiatus hernia (1).
      Inter-observer agreement ranged from 0.76 to 1 between senior radiologists and
      from 0.76 to 1 between resident and senior radiologists. The average time of
      image interpretation ranged from 14 to 15 minutes. CONCLUSION: ECG-gated whole
      chest CT angiography appears as a promising tool for the evaluation of acute
      chest pain. Combined evaluation of appearance and function of the myocardium can
      reveal additional interesting information.

PMID- 19752789
TI  - [Bilateral primary adrenal lymphoma: a report of two cases].

PMID- 19752790
TI  - [Portal venous phase CT of the abdomen and pelvis: do not forget the prostate!].

PMID- 19752791
TI  - [Diagnosis of acute myocardial infarction on cardiac CT based on kinetic and
      perfusion abnormalities].

PMID- 19752792
TI  - [Turcot syndrome: a case report].

PMID- 19752794
TI  - [Answer to june e-quid. Imaging features of meningioma in a patient with
      underlying myeloproliferative disorder: consider chloroma].

PMID- 19752793
TI  - [Hepatic Epithelioid hemangioendothelioma: a rare liver tumor].
AB  - Epithelioid hemangioendothelioma of the liver is a rare primary malignant tumor
      of vascular origin. It most frequently occurs in middle age adults and clinical
      findings are non-specific. Histological diagnosis may be difficult to achieve
      with lesions containing a large myxoid component, and immunohistochemical
      staining is required. A few imaging features may suggest the correct diagnosis,
      and radiologists should be familiar with these findings. We will illustrate the
      potential role of PET-CT at the time of initial presentation. Prognosis is
      variable and optimal management is based on a case by case analysis, ranging from
      clinical and imaging follow-up to liver transplantation.

PMID- 19752797
TI  - [Case No.1. Juvenile papillomatosis nodule: doubt about cancerogenesis].

PMID- 19752798
TI  - [Case No.2 Intra-alveolar hemorrhage localized on thrombosis of the right
      inferior pulmonary vein on lesion of post-tuberculous fibrous mediastinitis].

PMID- 19752799
TI  - [Case no 3. Thymic lymphoma of the MALT type. Gougerot-Sjogren syndrome. Diffuse
      infiltrating pneumopathy (lymphocytic interstitial pneumopathy)].

PMID- 19752800
TI  - [Case No. 4. Wegener's granulomatosis].

PMID- 19752801
TI  - [Case No 5. Allergic bronchopulmonary aspergillosis or Hinson-Peppys disease ].

PMID- 19752802
TI  - [Case No. 6. Pleural fibroma or solitary fibrous tumor of the pleura].

PMID- 19752803
TI  - [Retraction of the liver capsule: a useful imaging finding].

PMID- 19752804
TI  - [The fifties].

PMID- 19752805
TI  - [The Journal of Radiology 1947-1956].

PMID- 19752806
TI  - [Arterial spin labeling: state of the art].
AB  - Arterial spin labeling (ASL) perfusion MR imaging is a technique by which water
      from circulating arterial blood is magnetically labeled and acts as a diffusible
      tracer allowing non-invasive measurement of cerebral blood flow. In this paper,
      the technique and current applications in neuroimaging will be reviewed. CURRENT
      STATUS: First, the technical principles of ASL will be reviewed and both
      available techniques (continuous and pulsed ASL) explained. A review of the
      literature will demonstrate advances with the techniques of ASL and its clinical
      impact. Clinical research involves normal volunteers and patients with ischemic
      and tumoral pathologies. CONCLUSION: Recent technical advances have improved the
      sensitivity of ASL perfusion MR imaging. The routine clinical use of ASL at 3.0
      Tesla should increase over the next few years.

PMID- 19752807
TI  - [Imaging features of cavernous hemangiomas of the orbit].
AB  - Cavernous hemangioma is the most frequent benign tumor of the orbit. The clinical
      presentation is that of a slowly progressive intra-orbital mass with variable
      degree of exophthalmos. CT typically demonstrates the presence of a well defined
      oval or rounded shaped mass but MRI provides superior evaluation of the orbit.
      The tumor is intra-conal in 80% of cases and usually shows T1W hypo-isointensity,
      T2W hyperintensity and heterogeneous contrast enhancement that becomes more
      homogeneous on delayed imaging (5 minutes).

PMID- 19752808
TI  - [Impact of PACS implementation in a university center on radiology practice
      profile].
AB  - PURPOSE: To determine the impact of a joint PACS implementation at a university
      medical center and cancer center on the radiology practice profile. Materials and
      methods. In 5 radiology sections, patients, selected based on identifiable acute
      or chronic diseases, underwent US, CT or MRI. Data were collected on datasheets
      from each provider with regards to clinical history, availability of prior
      examinations, description of patient management during the different phases of
      the examination, duration of examinations, and satisfaction. Data obtained prior
      to PACS implementation and 6-12 months and 30-36 months after implementation were
      compared. RESULTS: A total of 1098 datasheets were collected. Hard copy readings
      rapidly decreased. Comparison with prior examinations improved (+20.6% to 25.6%)
      as well as frequency of post-processing (+29%). The time required for image
      management was much more reduced for technologists (-75%) than for physicians (
      23%). PACS implementation only temporarily improved the availability of radiology
      reports and the distribution of work between senior and junior radiologists. User
      satisfaction, initially high, progressively decreased due to saturation of the
      archival capabilities. CONCLUSION: PACS implementation in a large university
      center improves the efficiency of image acquisition but does not solve some of
      the inefficiencies of hospital organization.

PMID- 19752809
TI  - [Comparison of 64 MDCT coronary CTA and coronary angiography in the detection of
      coronary artery stenosis in low risk patients with stable angina and acute
      coronary syndrome].
AB  - PURPOSE: To determine the accuracy of 64 MDCT coronary CTA (CCTA) compared to
      coronary angiography in low risk patients with stable angina and acute coronary
      syndrome and determine the number of significant coronary artery stenoses ( 50%)
      in these patients. Materials and methods. Fifty-five patients underwent CCTA
      using a 32 MDCT unit with z flying focus allowing the acquisition of 64 slices of
      0.6 mm thickness as well as coronary angiography (gold standard). Nine patients
      were excluded due to prior coronary artery bypass surgery (n=4), insufficient
      breath hold (n=3), calcium scoring>1000 (n=1) and delay between both examinations
      over 4 months (n=1). Forty-six patients: 27 males and 19 females were included.
      CCTA results were compared to coronary angiography per segment and artery with
      threshold detection of stenoses 50%. The degree of correlation between both
      examinations was performed using a regression analysis with a Pearson correlation
      coefficient<0.05 considered significant. RESULTS: The overall accuracy of CCTA
      was 90%; limitations related to the presence of calcifications, motion artifacts
      or insufficient vessel opacification. The correlation for all analyzed segments
      was 96.4%. Thirty-eight of 50 significant stenoses seen on coronary angiography
      were correctly detected on CCTA. Sensitivity, specificity, PPVC and NPV for
      detection of stenoses 50% were 76%, 98.3%, 80.3% and 97.7% respectively.
      Evaluation per segment had a NPV of 96.8% (interventricular and diagonal
      segments) to 100% (main trunk). CONCLUSION: Our results for specificity and NPV
      are similar to reports from the literature. This suggests that CCTA in this
      clinical setting may replace coronary angiography.

PMID- 19752810
TI  - [Liver capsule retraction adjacent to a circumscribed liver lesion: review of 26
      cases with histological confirmation].
AB  - PURPOSE: To review the histological features of 26 circumscribed liver lesions
      associated with liver capsule retraction and discuss the differential diagnosis
      while evaluating for the presence of fibrous stromal reaction. Materials and
      methods. Retrospective study performed between January 2005 and June 2008
      including 26 patients: 18 males and 6 females, without history of cancer, aged
      between 42 and 82 years (mean age: 64.5 years), presenting with liver capsule
      retraction adjacent to a circumscribed liver lesion detected on CT or MRI. A
      single lesion was present in 17 patients, and multiple lesions were present in 9
      patients. All liver lesions were biopsied with semi-quantitative evaluation of
      fibrous stromal reaction. RESULTS: Twenty-one patients had benign or malignant
      liver tumors and 5 patients had confluent hepatic fibrosis. Twenty of 21 liver
      tumors were malignant (95.2%): 3 intra-hepatic cholangiocarcinoma, 17 cases of
      metastatic disease including colorectal carcinoma (n=8), bronchogenic carcinoma
      (n=1), pancreatic carcinoma (n=4), esophageal carcinoma (n=1), breast carcinoma
      (n=1), gallbladder carcinoma (1) and endocrine neoplasm of the pancreas (n=1),
      and 1 case of liver sclerosing angioma (n=1). There was no case of hepatoma.
      Excluding the 5 cases of confluent hepatic fibrosis, fibrous stromal reaction was
      present in 15 of 21 cases. CONCLUSION: The presence of capsular retraction next
      to a circumscribed liver lesion, while non-specific, is suspicious. In keeping
      with previous reports, metastases were frequently the cause and intrahepatic
      cholangiocarcinoma was the most frequent primary tumor. In patients with chronic
      hepatocellular disease, confluent fibrosis was a frequent etiology. The fibrous
      component of the underlying malignant lesion along with its subcapsular location
      appear to be determining factors in the development of capsular retraction.

PMID- 19752811
TI  - [Role of polyvidone-iodine ablation in the management of symptomatic renal
      cysts].
AB  - OBJECTIVE: To assess prospectively the results of percutaneous sclerotherapy with
      povidone-iodine of symptomatic renal cysts in adults. METHODS: Fifty two patients
      were included in this study from august 2004 to november 2006. The operative
      indication was: pain (41 cases), urinary tract compression (8 cases), and very
      large cyst (3 cases). The preoperative assessment (site and dimensions of the
      cyst) always included ultrasonography. CT scan, for morphological assessment, was
      performed in 39 cases. RESULTS: The mean age of patients was 63 years (47-75
      years). The mean diameter was 76 mm. The cysts were punctured in all the cases
      directly under local anaesthesia and guided by sonography. The procedure was very
      well tolerated in every case, with external drainage for 72 hours. Clinical
      regression was complete in 48 cases (92%), with total ultrasonographic
      disappearing of the cysts in 31 cases (60%) with a mean follow-up of 14 months (3
      29 months). CONCLUSION: Percutaneous sclerotherapy with povidone-iodine is a
      safe, effective and reproducible treatment of symptomatic renal cysts in adults.

PMID- 19752812
TI  - [Acute appendicitis in an incarcerated crural hernia: a case report].

PMID- 19752813
TI  - [Multiple aneurysms of the thoracoabdominal aorta as a presentation of
      tuberculosis].

PMID- 19752814
TI  - [Neurofibroma of the cranial vault in a patient with neurofibromatosis type 1].

PMID- 19752815
TI  - [Carcinoma arising in ectopic breast tissue: a case report].

PMID- 19752816
TI  - [Answer to July-August e-quid. The crazy-paving sign: a characteristic but non
      specific feature of alveolar proteinosis].

PMID- 19752821
TI  - [Appropriateness criteria for the use of cardiac CT and MRI: recommendations of
      the French Society of Cardiology and French Society of Radiology].

PMID- 19752823
TI  - [Current indications for cardiac CT].
AB  - There is a need to define the current indications for coronary CT angiography
      (CCTA) even as technology continuously evolves. CCTA using 64 MDCT units has
      shown to be highly accurate for diagnosis of stenoses >or=50% on selected
      populations. It is currently used for its negative predictive value (96-98%).
      Stenosis quantification remains inferior to conventional coronary angiography
      with tendency to overestimate stenoses <70%. For diagnosis of coronary artery
      disease, CCTA is considered based on clinical findings (pre-test probability of
      coronary artery disease) and presence of myocardial ischemia on other functional
      studies. The main appropriate indications include: In the setting of acute
      coronary syndrome, CCTA excludes coronary artery disease with excellent NPV and
      good negative likelihood ratio (0.05) when ECG is non-contributory, 2 consecutive
      troponin levels at 6 hours are negative in a patient with low risk of coronary
      artery disease. In the setting of stable angina or atypical precordial chest
      pain, CCTA is indicated in patient with low to medium risk when functional test
      are non-contributory or unavailable, or ECG is non-interpretable. CCTA is a
      complement to coronary angiography for morphological evaluation of some lesions
      prior to angioplasty and stent placement (long segment occlusion, proximal
      lesions involving LAD and circumflex arteries). In selected patients, CCTA may
      replace coronary angiography prior to valvular surgery.

PMID- 19752822
TI  - [Cardiac CT: technical considerations].
AB  - The possibility to perform cardiac and coronary imaging was a major driving force
      behind an ongoing, rapid evolution of scanner technology, accompanied by
      improvements of software and post-processing tools. The most recent generations
      of MDCT with the ability to acquire at least 64 slices simultaneously allow
      relatively robust morphological and functional imaging of the heart. By nature of
      its target, the continuously moving heart, cardiac CT is technically more
      challenging than other CT applications. Also, rapid technical development
      requires constant adaptation of acquisition protocols. The present manuscript
      summarizes the current state of technology of cardiac CT. Included are
      considerations regarding appropriate patient selection, patient medication,
      contrast enhancement, acquisition and reconstruction parameters, image display
      and analysis techniques with a special emphasis on radiation dose and all
      possible measures to keep the dose. It does not constitute a meta-analysis of
      published literature, but merely reflects an expert consensus on the current
      technical aspects of cardiac CT imaging.

PMID- 19752824
TI  - [Cardiac MRI: technical considerations].
AB  - Establishing a clinical cardiovascular magnetic resonance imaging (MRI) program
      needs a dedicated technical surroundings as well as a specific and expert staff.
      These guidelines based either on proofs or on expert consensus are stated in
      order to help the physicians to reach or maintain the competence required for
      clinical use of cardiovascular MRI. After the general safety statements, the
      guidelines are focused on hardware and software requirements, the MRI sequences
      and views, the post-acquisition analysis, and the staff. Specific safety concerns
      are then approached, more particularly stress testing MRI.

PMID- 19752825
TI  - [Current indications for cardiac MR imaging].
AB  - MRI has acquired over the years a role in the evaluation of cardiovascular
      pathology especially with regards to its ability to assess right and left
      ventricular function and delayed postcontrast "viability" sequences. Current
      class I clinical indications include: viability for patients with ischemic
      cardiomyopathy and acute coronary syndrome, etiology and prognostic evaluation of
      non-ischemic cardiomyopathies including myocarditis and arrhytmogenic right
      ventricular cardiomyopathy, chronic pericarditis and cardiac masses, non-urgent
      aortic aneurysm and dissection, congenital cardiopathies: vascular malformations
      and follow-up after curative or palliative surgery. MRI provides a complete non
      operator dependent evaluation, and is particularly useful for follow-up since it
      may be repeated due to its absence of ionizing radiation

PMID- 19752826
TI  - [Technological advances in cardiac CT].
AB  - The SFR-SFC presents guidelines dedicated to cardiac and coronary imaging using
      CT in the area of indications, technological requirement including both hardware
      and software, patient conditioning, CT protocols and related results concerning
      radiation dose, image quality and diagnostic value. These guidelines are based
      either on up-dated medical literature proofs and/or on expert consensus.

PMID- 19752827
TI  - [Recommendations for training in cross-sectional cardiac imaging].
AB  - The recent and future advancements that are known in the field of cardiac imaging
      imply an optimal training of the operators. This training concerns medical
      specialists whether originating from radiology or cardiology. The training of the
      medical specialists in cardiac imaging entitles 3 main essential steps: The basic
      training taking place within each specialty, allowing the fellow to get
      acquainted with the clinical and technical basics. The specialized training,
      delivered principally in post-residency. This training must include an upgrading
      of each specialty in the domain that does not concern it (a technical base for
      the cardiologist, a physio-pathological and clinical base for the radiologist).
      It must include a specific theoretical training covering all aspects of cardiac
      imaging as well as practical training in a certified training centre. The
      continuous medical training and maintenance of skills that allow a sustained
      activity in the field and the obligation to regularly participate in the actions
      of specific validated training. The different aspects of these rules are exposed
      in this chapter.

PMID- 19752828
TI  - [Postoperative imaging of the abdomen and chest: humility and multidisciplinary
      approach].

PMID- 19752829
TI  - [Imaging of the postsurgical liver].
AB  - The appearance of the normal postsurgical liver and of potential complications
      specific to the type of liver resection performed (partial hepatectomy, cyst
      fenestration, RF ablation) must be well known by radiologists for early detection
      and treatment of postoperative complications. Early postoperative imaging of the
      liver aims at detecting vascular, biliary and extrahepatic complications and
      relies mainly on Doppler US and CT.

PMID- 19752830
TI  - [Imaging of the postoperative biliary tract].
AB  - For a long time, imaging of the biliary tract after surgical procedures was
      performed with invasive procedures such as endoscopic retrograde
      cholangiopancreatography or percutaneous transhepatic cholangiography. Due to
      recent advances in diagnostic imaging, non-invasive techniques are now favored.
      While US remains the initial imaging modality, it is frequently followed by CT
      and/or MRCP. Image interpretation should always be performed in keeping with
      clinical and laboratory findings as well as the type of surgical procedure. The
      most appropriate imaging modality is selected based on these data. In patients
      with jaundice or biliary tract stenosis, MRCP, with use of an optimal technique
      and 3D acquisition, is the imaging modality of choice. In non-jaundiced patients
      with non-distended biliary tract and suspected bile leak, MRCP should be
      completed by the injection of a liver-specific contrast agent with biliary
      excretion to achieve non-invasive biliary tract opacification. In patients with
      malignancy, CT is preferred due to its high spatial resolution and ability to
      demonstrate small anastomotic tumor recurrences. CT should also be performed in
      patients with suspected hepatic artery or portal vein injury in addition to
      biliary tract injury or to detect distant complications.

PMID- 19752831
TI  - [Postoperative imaging of the pancreas and duodenum].
AB  - Pancreatic surgery is a frequent therapeutic approach for benign and malignant
      conditions. CT has become the imaging method of reference to detect early
      postoperative complications and to detect recurrent disease during long-term
      follow-up. Knowledge of the normal postoperative anatomy is essential for
      accurate interpretation of CT scans. The purpose of this paper is to illustrate
      the normal and abnormal CT appearances of common surgical procedures involving
      the pancreas.

PMID- 19752832
TI  - [Postoperative imaging of the cardia and stomach].
AB  - In addition to treatment of complications from peptic ulcer disease,
      gastroesophageal reflux and gastric cancer, bariatric surgical procedures have
      increased over the recent years. Complications after gastric surgery are imaged
      with upper gastrointestinal contrast studies and CT. This imaging is not always
      easy and it is important for radiologists to know the different types of surgical
      techniques and to be familiar with normal postoperative anatomical and
      pathological findings.

PMID- 19752833
TI  - [Postoperative imaging after colorectal surgery].
AB  - Surgery for the treatment of colorectal diseases has been evolving rapidly
      recently. In addition to classical surgical procedures (colectomy,
      abdominoperineal resection), new surgical procedures include coloproctectomy with
      creation of an ileoanal anastomosis and ileal pouch, pelvic reconstructions
      (omentoplasty, placement of myocutaneous flaps) and creation of different colic
      anastomoses after anterior rectal resection. Even if computed tomography and
      fluoroscopic contrast examinations are still commonly used to assess
      postoperative changes and complications, especially infections, pelvic magnetic
      resonance imaging is useful to depict postoperative changes, detect complications
      such as fistulas and tumor recurrence in patients who have undergone surgery for
      primary or recurrent rectal disease. The main surgical techniques, their
      respective indications and postsurgical imaging features will be discussed. The
      main complications and imaging work-up will also be reviewed.

PMID- 19752834
TI  - [Postoperative imaging of the peritoneum and abdominal wall].
AB  - CT scan is the gold standard for follow-up after abdominal surgery and diagnosis
      of postoperative complications. During the immediate postoperative period,
      asymptomatic and rapidly regressing peritoneal collections of fluid and gas are
      often present. Transient ileus is classically present as well. The diagnosis of
      postoperative peritonitis is difficult on imaging; fluid collections are frequent
      and easily detected. The main postoperative peritoneal complication is small
      bowel obstruction, either early and due to inflammatory changes, or delayed and
      due to adhesions or less frequently to other causes, including transmesenteric
      hernia. Other rare complications include desmoid tumors and gossypiboma. Wall
      complications, after laparotomy as well as laparoscopic surgery, are mainly
      hematoma, infections and wound hernia.

PMID- 19752835
TI  - [Thoracic surgery: the major surgical procedures].
AB  - The most frequent thoracic surgeries are performed for the treatment of primary
      lung cancer and pleural mesothelioma. For lung cancer, the standard procedures
      are pneumonectomy and lobectomy with associated mediastinal lymphadenectomy. In
      order to avoid pneumonectomy, extended lobectomy with sleeve bronchoplasty and/or
      angioplasty can be done. When adjacent organs are involved, extended resections
      are accepted (chest wall, vena cava...). For small lesions (<2 cm) without lymph
      nodes involvement and for patients with limited respiratory function,
      segmentectomy is an option (results under evaluation). For the treatment of
      pleural mesothelioma, the accepted oncologic resection is extra-pleural
      pneumonectomy extended to the diaphragm and pericardium. This surgical indication
      requires careful evaluation of tumour staging and patient's capacities. The
      morbidity and mortality of these resections require comprehensive follow-up
      (clinical, biological (including blood gases) and radiological).

PMID- 19752836
TI  - [Postoperative chest: normal imaging features].
AB  - Chest radiographs and CT are especially useful for the follow-up of patients
      after lung resection. The purpose of this paper is to illustrate normal
      postsurgical imaging findings that differ according to the type of surgery
      (pneumonectomy, lobectomy, segmentectomy and wedge resection). Anatomic changes
      induced by surgery affect the remaining lung, pleura and chest wall, mediastinum
      and diaphragm. After pneumonectomy, there is accumulation of fluid in the post
      pneumonectomy space, progressive chest retraction with mediastinal shift toward
      the operated side and elevation of the ipsilateral hemidiaphragm. After
      lobectomy, there is hyperexpansion of the remaining lung, mediastinal shift and
      intercostal space narrowing. Theses findings are different according to the delay
      after surgery. Knowledge of the variable imaging features is necessary to detect
      complications and to provide appropriate follow-up of the primary disease.

PMID- 19752837
TI  - [Postoperative complications after thoracic surgery].
AB  - Postoperative complications after pneumonectomy, lobectomy, or wedge resection
      are relatively frequent and potentially significant. Chest radiographs and CT
      have a crucial role in the early detection and prompt management of these
      complications. The purpose of this paper is to illustrate the most frequent or
      severe complications, based on the timing of occurrence. Early complications
      include bronchopleural fistula, empyema, atelectasis, pneumonia, hemothorax,
      chylothorax, pulmonary edema, lobar torsion, cardiac hernia, gossypiboma and
      esophagopleural fistula. Late complications include bronchopleural fistula,
      esophagopleural fistula, postpneumonectomy syndrome, chest wall arteriovenous
      fistula and local tumor recurrence.

PMID- 19752838
TI  - Assessing rates and predictors of tachyphylaxis during the prevention of
      recurrent episodes of depression with venlafaxine ER for two years (PREVENT)
      study.
AB  - BACKGROUND: Antidepressant tachyphylaxis describes the return of apathetic
      depressive symptoms, such as fatigue and decreased motivation, despite continued
      use of a previously effective treatment. METHODS: Data were collected from a
      multiphase, doubleblind, placebo-controlled study that assessed the efficacy of
      venlafaxine extended release (ER) during 2 sequential 1-year maintenance phases
      (A and B) in patients with recurrent major depressive disorder (MDD). The primary
      outcome was the cumulative probability of tachyphylaxis in patients receiving
      venlafaxine ER, fluoxetine, or placebo. Tachyphylaxis was defined as Rothschild
      Scale for Antidepressant Tachyphylaxis (RSAT) score </= 7 in patients with prior
      satisfactory therapeutic response. A Kaplan-Meier estimate of the cumulative
      probability of not experiencing tachyphylaxis, and a 2-sided Fisher exact test
      was used to assess the relationship between tachyphylaxis and recurrence.
      RESULTS: The maintenance phase A population was comprised of 337 patients
      (venlafaxine ER [n = 129], fluoxetine [n = 79], placebo [n = 129]), whereas 128
      patients (venlafaxine ER [n = 43], fluoxetine [n = 45], placebo [n = 40]) were
      treated during maintenance phase B. No difference in the probability of
      experiencing tachyphylaxis were observed between the active treatment groups
      during either maintenance phase; however, a significant difference between
      venlafaxine ER and placebo was observed at the completion of maintenance phase A.
      A significant relationship between tachyphylaxis and recurrence was observed.
      LIMITATIONS: Despite demonstrating psychometric validity and reliability, the
      current definition of tachyphylaxis has not been widely studied. CONCLUSIONS:
      Although no significant differences were observed in the probability of
      tachyphylaxis among patients receiving active treatment, the relationship between
      tachyphylaxis and recurrence suggests that tachyphylaxis may be a prodrome of
      recurrence.

PMID- 19752839
TI  - Analysis of depressive symptoms in patients with major depressive disorder
      treated with desvenlafaxine or placebo.
AB  - BACKGROUND: The aim of this study was to evaluate the impact of desvenlafaxine on
      a broad range of major depressive disorder (MDD) symptoms. METHODS: Data were
      pooled from 9 double-blind, randomized, placebo-controlled, 8-week studies of
      desvenlafaxine in adult outpatients with MDD. Intent-to-treat participants
      received fixed- (50, 100, 200, or 400 mg/d; n = 1342) or flexible-dose (100 to
      400 mg/d, n = 463) desvenlafaxine or placebo (n = 1108). Final on-therapy scores
      for individual items of the 17-item Hamilton Rating Scale for Depression (HAMD17)
      and the Montgomery Asberg Depression Rating Scale (MADRS) were compared between
      groups using analysis of covariance. Efficacy at different doses was examined
      using the subset of fixed-dose studies. RESULTS: Based on differences in adjusted
      mean changes from baseline (desvenlafaxine vs placebo), statistically significant
      advantages with desvenlafaxine (50 to 400 mg/d, all doses pooled) vs placebo were
      seen for 10 of the 17 HAM-D17 items: depressed mood (-0.4; P < 0.001), feelings
      of guilt (-0.2; P < 0.001), suicide (-0.1; P < 0.001), late insomnia (-0.1; P =
      0.001), work and activities (-0.2; P < 0.001), psychomotor retardation (-0.1; P <
      0.001), agitation (-0.1; P < 0.001), psychic anxiety (-0.3; P < 0.001), general
      somatic symptoms (-0.2; P < 0.001), and genital symptoms (-0.1; P = 0.003).
      Desvenlafaxine (50 to 400 mg/d, pooled) was significantly better than placebo on
      all MADRS items (range: -0.1 to -0.5; all P </= 0.019), except "reduced appetite"
      (-0.01, P > 0.05). Symptom relief was similar with all desvenlafaxine doses
      examined, including 50 mg/d. CONCLUSIONS: Shortterm desvenlafaxine therapy (50 to
      400 mg/d) improved a broad range of emotional and physical symptoms in
      outpatients with MDD.

PMID- 19752840
TI  - Efficacy of omega-3 fatty acids in mood disorders - a systematic review and
      metaanalysis.
AB  - OBJECTIVES: Existing efficacy trials of Omega-3 (omega-3) fatty acids in mood
      disorders have yielded inconsistent results. The current paper is an effort to
      provide a systematic review and meta-analysis to evaluate efficacy of omega-3
      fatty acids in treatment of mood disorders. DESIGN: We searched Medline, Embase,
      PsychInfo, and the Cochrane Controlled Trials registry up to June 2008 for
      randomized trials investigating efficacy of omega-3 fatty acids in mood
      disorders.We conducted random effects meta-analyses.We used the I2 statistic to
      quantify between-study inconsistency, and conducted pre-specified subgroup
      analyses to explore potential explanations for inconsistency. OBSERVATIONS: We
      included 21 trials in our systematic review and found 13 trials to be eligible
      for meta-analysis. The pooled standardized mean difference in depressed mood
      states (n = 554 in 12 trials) was -0.47 (95% CI:-0.92,-0.02; I2 = 82.7; p = 0.07)
      and in manic mood states (n = 126 in 4 trials) was 0.22 (95% CI: -0.21, 0.65; I2
      = 40.5; p = 0.31).We did not identify any treatment- subgroup interaction across
      forms of omega-3 fatty acids preparations (P = 0.99) or patient diagnosis
      (bipolar vs. unipolar depressive disorder; P = 0.96); there was a significant
      correlation between omega-3 fatty acids dose and treatment effect on depressive
      symptoms (r = 0.5, p = 0.04), but not on manic symptoms (P = 0.3). CONCLUSIONS:
      The available evidence suggests that omega-3 fatty acids are a potential
      treatment of depressive disorders, but not mania. The unexplained between-study
      inconsistency and imprecision of the pooled estimates mitigate this suggestion.
      Large randomized placebo-controlled trials are needed to better estimate the
      value of this intervention for patients with depression.

PMID- 19752841
TI  - A systematic review of augmentation strategies for patients with major depressive
      disorder.
AB  - Major depressive disorder (MDD) is a leading cause of disability worldwide.
      Clinicians need to determine the most appropriate and effective interventions for
      patients who do not benefit from first-line treatment. A systematic review of the
      literature on augmentation strategies for major depression was conducted. A total
      of 32 eligible studies were included in the final review. Identified augmentation
      strategies included lithium, thyroid hormone, buspirone, stimulant drugs
      (methylphenidate and modafinil), and atypical antipsychotics (olanzapine,
      quetiapine, aripiprazole, and risperidone). Additional studies used other
      augmentation strategies (yohimbine, atomoxetine, inositol, testosterone, and
      lamotrigine), or combinations with a second antidepressant (mianserin,
      mirtazapine, and desipramine). There was no evidence of clinical efficacy as
      measured by response in augmentation with buspirone, testosterone,
      methylphenidate, yohimbine, inositol, and atomoxetine. Although some studies of
      combined antidepressant therapy and lithium augmentation did show statistically
      significant clinical effects, results were inconsistent across studies. The only
      eligible study of thyroid augmentation was positive, though this study evaluated
      patients treated with tricyclic antidepressants. It is possible due to small
      sample sizes, that some of the trials failed to detect significant differences
      versus placebo because of inadequate statistical power. Adjunctive therapy with
      atypical antipsychotics showed higher response rates compared with antidepressant
      monotherapy and placebo but also had more withdrawals due to adverse events.
      Given ongoing concerns with the longer term tolerability and safety of the
      atypical antipsychotics, future research will need to investigate optimal
      duration of augmentation therapy in patients with major depressive disorder who
      do not respond to first line therapy.

PMID- 19752842
TI  - Neonatal outcomes with the use of lamotrigine for bipolar disorder in pregnancy
      and breastfeeding: a case series and review of the literature.
AB  - The treatment of bipolar disorder in pregnant women and the postpartum period is
      a complex clinical issue requiring careful consideration of the risks involved in
      using psychotropic medications versus the benefits of successfully managing this
      chronic illness. We present three cases of women exposed to lamotrigine during
      pregnancy and breastfeeding, with follow up of their infants until 15-18 months
      of development.

PMID- 19752843
TI  - Switching to duloxetine remits ziprasidone - associated urinary incontinence and
      improves neuropsychiatric behavior in dementia: possible relationship of
      incontinence to 5HT2 receptor blockade.
AB  - OBJECTIVES: Urinary incontinence arising in dementia lowers patient quality of
      life, predicts caregiver burden and nursing home placement, and predisposes to
      adding additional medicines that can further impair cognition, behavior, and
      function. An understanding of incontinence pharmacology can help the clinician
      predict and manage this adverse event in treating patients with dementia.
      EXPERIMENTAL DESIGN: Case report. PRINCIPAL OBSERVATIONS: We encountered a
      patient with Alzheimer's disease and vascular dementia who developed urinary
      incontinence and parkinsonism when ziprasidone was added to the regimen for
      behavioral concerns.When he was switched to duloxetine, the incontinence and
      parkinsonism resolved whereas improvements in perseveration, irritability,
      paranoia, and agitation persisted. CONCLUSIONS: While a pharmacokinetic
      explanation is unlikely, the best evidence suggests that ziprasidone-mediated
      serotonin 5HT2 receptor blockade may explain the reversible incontinence, with an
      adrenergic alpha-1 receptor mechanism considered to be less likely. Patients on
      5HT2 antagonist drugs, including atypical antipsychotics, should be observed for
      incontinence. In the event of incontinence developing in the context of these
      agents, duloxetine may represent a potential pharmacological alternative in some
      cases. Duloxetine may improve neuropsychiatric symptoms in dementia through its
      effects on serotonin, norepinephrine, and frontal dopamine.

PMID- 19752844
TI  - Idiopathic spontaneous intestinal perforation: a distinct pathological entity in
      the preterm infant.
AB  - AIM: Necrotizing enterocolitis (NEC) is the most common cause of intestinal
      perforation in newborn children. A novel condition of idiopathic spontaneous
      intestinal perforation (SIPI) was recently described, which does not show
      clinical and diagnostic features of NEC. The aim of the present study was to
      define clinical peculiarities and potential risk factors in newborns by comparing
      SIPI and NEC patients. METHODS: In the last six years, 85 preterm infants have
      necessitated surgical counseling for acute abdominal conditions. Among them, 13
      underwent emergency surgery, 6 for SIPI and 7 for NEC respectively. Patients were
      then subdivided into three groups: group 0: 72 infants who did not need surgery;
      group I: 6 patients with SIPI; group II: 7 patients with NEC. Some variables were
      retrospectively analyzed and were compared by means of chi(2) test with a
      significant value of P<0.05. RESULTS: No association emerged between patient's
      sex gender (P=0.691), membrane ruptures (P=0.400) and maternal infection
      (P=0.415). A correlation was observed between pneumoperitoneum and SIPI/NEC
      (P=0.000). The study on group I and II showed a lower gestational age (27.3 as
      compared to 30.28 weeks) and a higher number of membrane ruptures (4/6 as
      compared to 3/7) and of maternal infections (4/6 as compared to 3/7).
      CONCLUSIONS: This study showed that a determining factor for the etiopathogenesis
      of SIPI may be neonatal stress consequent to preterm birth. Infants under 28
      weeks of gestational age, with low birth weight, show a particular predisposition
      to SIPI, with a risk accounting to 96% of the present case series.

PMID- 19752845
TI  - The quality of life of children with pervasive developmental disorders.
AB  - AIM: Quality of life is increasingly the focus of attention by health,
      psychological and social services. Pervasive developmental disorders (PDD) are a
      group of psychiatric conditions in which the patient's clinical case history is
      characterized by disturbances in social interaction, deterioration of verbal and
      non-verbal communication, and presence of bizarre, limited and stereotyped
      activity. These disturbances affect multiple developmental areas and show up in
      very early stages of development, resulting in a permanent disorder. Many studies
      have sought to recognize causes and interventions for persons with PDD, however,
      they often take insufficient account of the effects these disorder can have on
      the lifestyle of patients and their families. These clinical case histories are
      so pervasive that they cause a disorder which upsets the equilibrium of the
      person's entire life. The aim of this study was to assess the effect of living
      with PDD on the person's quality of life and to highlight the factors that impact
      on the person and his/her family. METHODS: Both parents of 54 subjects (46 males
      and 8 females; age range 4-28 years) with diagnosed PDD (43 with autistic
      disorder, 2 with childhood disintegrative disorder, 3 with Asperger Syndrome, 6
      with pervasive development disorder NAS) were enrolled in the study. The subjects
      affected with PDD were recruited at the AGSAS Onlus and IsMeC. Diagnosis was
      based on the criteria of the Diagnostic and Statistical Manual of Mental
      Disorders. Quality of life was assessed using the Italian version of the Impact
      of Childhood Illness Scale (Hoare and Russell, 1995). This scale consists of 30
      questions that investigate the effect of illness on children, parents and
      families. For each question, the parent was asked to rate two variables:
      frequency and importance. Another questionnaire was administered to obtain
      medical history, diagnostic and therapeutic data of the persons with PDD.
      RESULTS: Analysis of frequencies and percentages of questionnaire answers showed
      that the most important problems related to illness; specifically, according to
      the Frequency and Importance Parameters, the problems centered around self-care
      skills, difficulty in explaining the child's illness to others and looking after
      the child. The most important problems about the other children in the family
      concerned providing them with necessary attention and the restrictions their
      brother/sister's illness placed on their own activities. No significant
      correlations emerged between diagnosis type and answers on individual subscale
      items (Pearson's r). CONCLUSIONS: Our data show that PDD has a considerable
      impact on both the child's development and the entire family. Parents' answers
      demonstrated that their child's illness had consequences for the child and how
      the family coped with it. For this reason, attention should be directed at
      psychological and social aspects, as well as attitudes, manners, reactions and
      effects such disturbances can have on the entire family.

PMID- 19752846
TI  - Clinical, pathological and radiological survey of patients with Leigh syndrome.
AB  - AIM: The aim of this study was to evaluate the clinical, pathological and
      radiological survey of patients affected by Leigh syndrome. METHODS: Eleven
      patients with Leigh disease were evaluated at Dokuz Eylul University, School of
      Medicine, Department of Pediatric Neurology. All patients underwent neurological
      evaluation with detailed medical and family history. Muscle biopsy from
      quadriceps muscle, brain magnetic resonance imaging and brain magnetic
      spectroscopy were obtained. RESULTS: The patients were aged between 1 month and 8
      years (mean age: 2.29+/-2.58 years). The most common presentation findings were
      psychomotor retardation and acute metabolic encephalopathy. All patients had
      elevated lactate in the blood and/or cerebrospinal fluid. Except in two patients,
      brain magnetic resonance imaging revealed abnormal symmetrical lesions in the
      brainstem and basal ganglia. Brain magnetic resonance spectroscopy revealed
      abnormal lactate peak in all patients. The muscle biopsy of two patients showed
      cytocrom-c oxidase deficiency and measurement of respiratory chain complex in one
      patient revealed complex I and IV deficiency. One patient was found to carry
      mitochondrial T8993C mutation. CONCLUSIONS: There are no specific markers for
      Leigh disease which lead to extensive work-up. The disease should be considered
      in patients who present progressive neurologic symptoms involving brainstem and
      basal ganglia.

PMID- 19752847
TI  - [Role of interactive music in oncological pediatric patients undergoing painful
      procedures].
AB  - AIM: The present study has examined whether interactive music may be considered
      an effective treatment for the attenuation of anxiety in oncological paediatric
      patients undergoing painful procedures (lumbar injection, bone marrow aspiration,
      osteomedullary biopsy and arterial catheter). METHODS: Thirty-nine tumour
      patients aged between 2 and 12 were randomised into 2 groups: Music (M) (N. 20)
      and Controls (N. 19) and were treated by M: conscious sedation and intervention
      of interactive music and C: sedation. The following factors were assessed:
      temperament on the Emotivity, Activity, Sociability scale, anxiety on the Yale
      preoperative anxiety scale (mYPAS), the induction compliance checklist (ICC),
      parent anxiety by cataloguing the trait-state anxiety inventory, and the degree
      of satisfaction of children, parents and staff using the Barrera questionnaires.
      Data significance was accepted with values of P<0.05. RESULTS: There was a fall
      in mYPAS values in M compared to C in the four phases of the process: Phase 1
      (P<0.05); Phase 2, 3 and 4 (P<0.01). For the ICC children with a score of <or=1,
      ''collaborated'', those with a score of >1 were ''non collaborators''; in the
      music group the trend was for an increase in the number of collaborating children
      (P<0.07). CONCLUSIONS: The M group presents a significant effect of attenuation
      of anticipatory anxiety and a tendency to great induction compliance compared to
      group C. The parents do not show any significant anxiety attenuation effect. The
      degree of satisfaction of children, parents and staff point to a positive role
      and a beneficial effect of interactive music on the occasion of painful
      procedures.

PMID- 19752848
TI  - Identification and management of dyslipidemic children.
AB  - Atherosclerotic cardiovascular disease is a leading cause of morbidity and
      premature mortality in Western countries and dyslipidemia is a recognized major
      cardiovascular risk factor. Evidences demonstrate that the atherosclerotic
      process begins early in childhood. Children showing dyslipidemia, as well as
      other cardiovascular risk factors, including hypertension, overweight/obesity and
      diabetes mellitus, are defined at high risk. To identify these children a
      selective screening between 2 to 10 years of age is necessary. This program must
      be performed to those children showing a familiarity for primary dyslipidemia
      and/or precocious cardiovascular events. These subjects need to undergo lipid
      biochemical analysis and assessment of other emergent risk factors (as ApoB, ApoA
      I and their ratio). Given that total cholesterol and low-density lipoprotein
      cholesterol (LDL-C) concentrations vary by age and sex, the use of percentile
      values according to these parameters is now recommended. In these high-risk
      subjects the first step to lower LDL-C under the value of 130 mg/dL is
      represented by an appropriate physical activities and Step II diet. This entails
      further reduction of saturated fatty acid intake to less than 7% of daily
      calories and of cholesterol to less than 200 mg/day (since two years of age).
      When diet therapy is insufficient to lower LDL-C to the acceptable concentration,
      the use of non-pharmacologic agents (soluble fibers, plant stanols, sterols) is
      suggested. The third approach, for children showing persistent elevated LDL-C
      >95(th) percentile, is represented by drugs, that are allowed only in children
      older than eight years.

PMID- 19752849
TI  - Current understandings and challenges in the management of cerebral palsy.
AB  - Cerebral palsy is a long recognized ''symptom-complex'' that is the most common
      cause of childhood physical impairment. A neurodevelopmental disability sub-type,
      it has an essential core of objective neuro-motor impairment and its present
      conceptualization includes explicit recognition of activity limitations and
      varying associated co-morbidities. This review explores this disorder's
      incidence, risk factors, complementary classification schemes, clinical
      evaluation, spectrum of heterogeneous causal etiologies, management challenges
      related to associated spasticity, movement disorders and co-existing conditions,
      outcomes and lifespan related changes. The goal of this review was to improve the
      clinician's understanding of what is presently known regarding cerebral palsy,
      its clinical challenges and appropriate case management.

PMID- 19752850
TI  - Neuroimaging and cerebral palsy in children.
AB  - Cerebral palsy (CP) is a description of a spectrum of central nervous system
      (CNS) impairments that affect mobility, communication, intellectual ability, and
      neurobehavior as a result of developmental brain dysfunction. CP is the most
      common contributor to motor disability in children with prevalence of about 2
      3/1000 live births globally. Presently, no curative therapies or successful
      methods of prevention on a population level are available for children with one
      of the cerebral palsy syndromes. Despite these challenges, orthopedic,
      rehabilitation, neuropharmacological, and other management interventions can help
      maintain mobility, prevent deformity, and promote quality of life for children
      with CP. Typically, the diagnosis of CP is based on clinical observations and
      parent concerns regarding delays in attaining motor milestones (e.g., rolling,
      sitting, crawling, walking), not on laboratory testing or neuroimaging. However,
      since 2004 the American Academy of Neurology (AAN) has recommended that
      neuroimaging of the CNS be part of diagnostic process for cerebral palsy.
      Although the guideline was initially met with controversy and criticism,
      neuroimaging has allowed a broader appreciation of timing of lesions, extent of
      white matter involvement, and the complexity of the motor spectrum of disability.
      In this article we shall describe the major types of neuroimaging techniques and
      review their roles in identification and evaluation of children with one of the
      cerebral palsy syndromes. The authors will focus on the emerging knowledge of how
      brain structure can inform us about children's functioning, especially among
      children with prematurity, recognizing that we are only beginning to understand
      brain plasticity and developmental resiliency.

PMID- 19752851
TI  - Rehabilitative therapies for the child with cerebral palsy: focus on family,
      function and fitness.
AB  - As most children with cerebral palsy (CP) survive into adulthood, the condition
      and its co-morbidities should be managed with a developmental and life-long
      perspective in the context of the family. A habilitation program for children
      with CP goes beyond treating the motor impairments. The themes ''Family, Function
      and Fitness'' are discussed to high-light some of the issues and challenges of
      the field of rehabilitation therapy for children with CP. This review is not
      intended to be exhaustive, but papers were selected that highlight some of the
      medical issues and challenges of the field of rehabilitation for children,
      adolescents and adults with CP.

PMID- 19752852
TI  - [Arachnoid cyst, hypoplasic temporal lobe and facial anomalies: a
      neurocristopathy].
AB  - The authors report on a patient which presented at birth facial anomalies similar
      to those of facial alcoholic syndrome (i.e. high forehead, wide nasal bridge,
      upturned nose, flat philtrum), low set ears, short neck. Successive-ly, also an
      arachnoid right temporo-polar cyst with hypoplasic right temporal lobe was
      diagnosed. They think that cerebral cyst, hypoplastic temporal lobe and facial
      anomalies are congenital. By the origin of facial and leptomeningeal structures
      from the neural crests, the authors conclude that facial, arachnoid and cerebral
      anomalies depend from the derangement of the neural crest development and that
      this complex syndrome is a neurocristopathy which can be ascribed to
      dysneurulation.

PMID- 19752853
TI  - [Multiple epiphyseal separations in a child with cerebral palsy and scurvy].
AB  - Scurvy is a dietary disease due to Vitamin C deficiency. Vitamin C is related to
      collagen synthesis and metabolism. Malnutrition, problems in bowel absorption,
      alcoholism and cerebral palsy are clearly often linked with scurvy, even it is no
      more common in the industrialized countries. Its clinical features are: asthenia,
      weight loss, appetite decrease, irritability, gingival or mucous lesions,
      porpora, follicular hyperkeratosis, musculoskeletal pain due to multiple
      fractures and subperiosteal bleedings, pseudoparalisis (frog-like position of
      legs) and refuse to walk. Authors report on a nine year-old girl with spastic
      quadriplegic cerebral palsy, who at the first examination showed deep anemia,
      fever and multiple epiphyseal separation of the right shoulder and the left knee.
      Diagnosis of scurvy was been made. The aim of this article was to underline the
      rarity and gravity of this disease, and its even more frequent appearance in
      children affected of cerebral palsy. Substitutive therapy consists on ascorbic
      acid supplementation. Complete restitutio ad integrum of skin-mucous injuries,
      such as gingival bleedings, was achieved within three months.

PMID- 19752854
TI  - Pott's disease in a two-year-old girl.
AB  - Fractures in children require a specific treatment depending on age. While
      obstetric fractures usually heal well even in case of significant dislocations
      and conservative therapy, the proportion of operative interventions among all
      pediatric fractures is increasing with age. Though the vast majority of fractures
      in childhood are still treated non-operatively, a trend towards early operative
      interventions and cast-free mobilization has been noticeable in the recent years.
      The methods of operative stabilization differ between the respective age groups:
      While K-wire osteosynthesis and a minimal invasive approach using elastic stable
      intramedullary nailing (ESIN) are common in the group of school aged children,
      the use of external fixation and plate osteosynthesis has been accepted for the
      treatment of fractures in adolescents. Bioresorbable implants do not yet play a
      decisive role in the management of pediatric fractures. This review is focusing
      on the current indications and concepts for stabilization of frequent pediatric
      fractures.

PMID- 19752855
TI  - Bilateral testicular torsion: an extremely tragic rare condition.
AB  - Bilateral intrauterine torsion of the testes and neonatal testicular torsion are
      rare conditions that sometimes result in a catastrophic event. Surgical
      exploration is mandatory and sometimes a second-look management should be
      considered. After describing a rare condition, the authors came to the conclusion
      that bilateral orchidectomy should be performed only in patients with bilateral
      necrotic testes.

PMID- 19752856
TI  - Imaging in-stent restenosis: an inexpensive, reliable, and rapid preclinical
      model.
AB  - Preclinical models of restenosis are essential to unravel the pathophysiological
      processes that lead to in-stent restenosis and to optimize existing and future
      drug-eluting stents. A variety of antibodies and transgenic and knockout strains
      are available in rats. Consequently, a model for in-stent restenosis in the rat
      would be convenient for pathobiological and pathophysiological studies. In this
      video, we present the full procedure and pit-falls of a rat stent model suitable
      for high throughput stent research. We will show the surgical procedure of stent
      deployment, and the assessment of in-stent restenosis using the most elegant
      technique of OCT (Optical Coherence Tomography). This technique provides high
      accuracy in assessing plaque CSAs (cross section areas) and correlates well with
      histological sections, which require special and time consuming embedding and
      sectioning techniques. OCT imaging further allows longitudinal monitoring of the
      development of in-stent restenosis within the same animal compared to one-time
      snapshots using histology.

PMID- 19752857
TI  - High-fat diet induces lung remodeling in ApoE-deficient mice: an association with
      an increase in circulatory and lung inflammatory factors.
AB  - Hypercholesterolemia is increasingly considered the basis for not only
      cardiovascular pathologies but also several complications affecting other organs
      such as lungs. In this study, we examined the effect of hypercholesterolemia on
      lung integrity using a mouse model (ApoE(-/-)) of high-fat (HF) diet-induced
      atherosclerosis. A 12-week HF diet regimen induced systemic production of TNF
      alpha, IFN-gamma, GMC-SF, RANTES, IL-1alpha, IL-2 and IL-12 with TNF-alpha as the
      predominant cytokine in ApoE(-/-) mice. Concomitantly, TNF-alpha, IFN-gamma and
      MIP-1alpha were detected in brochoalveolar lavage (BAL) fluids of these mice,
      coinciding with lung inflammation consisting primarily of monocytes/macrophages.
      Such lung inflammation correlated with marked collagen deposition and an increase
      in matrix metalloproteinase-9 activity in ApoE(-/-)mice without mucus production.
      Although TGF-beta1 was undetectable in the BAL fluid of ApoE(-/-) mice on HF
      diet, it showed a much wider tissue distribution compared with that of control
      animals. Direct exposure of smooth muscle cells to oxidized-LDL, in vitro,
      induced a time-dependent expression of TNF-alpha. Direct intratracheal TNF-alpha
      administration induced a lung inflammation pattern in wild-type mice that was
      strikingly similar to that induced by HF diet in ApoE(-/-) mice. TNF-alpha
      administration induced expression of several factors known to be critically
      involved in lung remodeling, such as MCP-1, IL-1beta, TGF-beta1, adhesion
      molecules, collagen type-I and TNF-alpha itself in the lungs of treated mice.
      These results suggest that hypercholesterolemia may promote chronic inflammatory
      conditions in lungs that are conducive to lung remodeling potentially through TNF
      alpha-mediated processes.

PMID- 19752858
TI  - Free fatty acids enhance breast cancer cell migration through plasminogen
      activator inhibitor-1 and SMAD4.
AB  - Obesity is a risk factor for breast cancer and is associated with increased
      plasma concentrations of free fatty acids (FFAs). We and others have demonstrated
      that FFA induces plasminogen activator inhibitor-1 (PAI-1) expression in a
      variety of cells. Emerging evidence supports elevation of PAI-1 as a prognostic
      marker for breast cancer. Therefore, we hypothesized that FFAs might increase
      expression of PAI-1 in breast cancer cells and facilitate breast cancer
      progression. Secreted PAI-1 was higher in invasive and metastatic MDA-MB-231
      cells compared with less invasive and non-metastatic Hs578T cells. Utilizing FFAs
      with different saturation and chain lengths, we demonstrated that linoleic acid
      induced expression of PAI-1 in MDA-MB-231 cells. Linoleic acid also induced in
      vitro migration of MDA-MB-231. By contrast, other FFAs tested had little or no
      effect on PAI-1 expression or migration. Linoleic acid-induced breast cancer cell
      migration was completely inhibited by virally expressed antisense PAI-1 RNA.
      Furthermore, increased expression of PAI-1 by FFAs was not detected in the SMAD4
      deficient MDA-MB-468 breast carcinoma cells. Electrophoretic mobility-shift assay
      confirmed that linoleic acid-induced expression of PAI-1 was mediated, at least
      in part, by SMAD4 in MDA-MB-231 cells. That linoleic acid induces PAI-1
      expression in breast cancer cells through SMAD4 provides a novel insight into
      understanding the relationships between two migration-associated molecules, FFAs,
      and PAI-1.

PMID- 19752861
TI  - Hurricane Katrina and chronic dialysis patients: better tidings than originally
      feared?
AB  - Besides victims with acute kidney injury, disasters may also affect the destiny
      of chronic dialysis patients. This Commentary discusses the article by Kutner et
      al. describing the outcome of chronic dialysis patients who were victims of
      Hurricane Katrina. The importance of advance disaster plans, including
      instructions to chronic dialysis patients, is emphasized. In addition, it is
      expected that specific recommendations, which are currently being prepared, will
      offer ad hoc advice to rescuers.

PMID- 19752862
TI  - Regulatory T cells: a brake on ischemic injury or an active promoter of tissue
      healing?
AB  - Gandolfo et al. report the key role played by regulatory T cells in modulating
      recovery from ischemic renal injury. The role of regulatory T cells in modulating
      ischemia-reperfusion injury in the kidney and other organs is discussed in this
      commentary.

PMID- 19752863
TI  - Zeta-crystallin: a tale of two cells.
AB  - Szutkowska et al. demonstrate that zeta-crystallin plays an essential role in the
      stabilization of the Na(+)/K(+)/2Cl(-) cotransporter mRNA in the medullary thick
      ascending limb. However, differential effects of experiments using small
      interfering RNA to knock down zeta-crystallin in proximal tubule and thick
      ascending limb cells suggest that additional proteins must contribute to the
      rapid turnover and selective stabilization of the various mRNAs during metabolic
      acidosis.

PMID- 19752864
TI  - Association of nephrolithiasis prevalence rates with ambient temperature in the
      United States: a re-analysis.

PMID- 19752866
TI  - A hypertensive woman with an abnormal abdominal X-ray. 'Page kidney' caused by a
      chronic subcapsular hematoma.

PMID- 19752867
TI  - Polycystic liver disease treated with therapeutic excision.

PMID- 19752869
TI  - Sacral rhizotomy: a salvage procedure in a patient with autonomic dysreflexia.
AB  - STUDY DESIGN: Case report. OBJECTIVES: To show the feasibility of sacral
      deafferentation as a salvage procedure to resolve life-threatening autonomic
      dysreflexia. SETTING: Paraplegic center in Switzerland. METHOD AND RESULTS: In a
      patient presenting with acute autonomic dysreflexia leading to cardiac arrest,
      sacral deafferentation could prevent further episodes of autonomic dysreflexia.
      CONCLUSION: In patients with spinal cord injury, autonomic dysreflexia can be
      triggered by the bladder even without detrusor overactivity. In these cases,
      sacral deafferentation may be the only salvage procedure to prevent further
      serious health problems. Thus, this procedure augments the armamentarium of
      urologists dealing with patients suffering from spinal cord lesions.

PMID- 19752868
TI  - Prevention and treatment of rheumatic heart disease in the developing world.
AB  - The prevalence of rheumatic heart disease (RHD) in industrialized countries has
      declined dramatically over the last century, but the disease remains an important
      global health problem with the burden of disease shouldered by developing
      countries. Indeed, data from epidemiologic surveys, which used echocardiography
      as the primary screening tool, indicate that the prevalence of RHD in developing
      nations might have been substantially underestimated. Despite the high burden of
      disease globally, there has never been a sustained and comprehensive
      international strategy to control RHD. The current focus of global efforts to
      combat the disease is on strengthening secondary prophylaxis strategies, although
      very few active national programs have been implemented. RHD will continue to
      cause high morbidity and mortality among the world's poorest populations unless
      current prevention initiatives expand and new programs are established.

PMID- 19752870
TI  - Bladder cancer in spinal cord injury patients.
AB  - STUDY DESIGN: Retrospective review. OBJECTIVE: Spinal cord injury is a known risk
      factor for bladder cancer. The risk of bladder cancer has been reported at 16-28
      times higher than the general population. Earlier studies have identified
      indwelling catheters as risk factors. We examined the characteristics of bladder
      cancers in a spinal cord injury (SCI) population. SETTING: Long Beach VA Hospital
      Spinal Cord Injury Unit, Long Beach, California. METHODS: We reviewed SCI
      patients seen and diagnosed with bladder tumors between January 1983 and January
      2007. Data collected included time since diagnosis, method of diagnosis, form of
      bladder management, pathologic type, treatment of the tumor, and outcome.
      RESULTS: A total of 32 patients with bladder cancer were identified out of 1319
      seen. Tumors found were 46.9% squamous cell carcinoma (SCC), 31.3% transitional
      cell carcinoma (TCC), 9.4% adenocarcinoma, and 12.5% mixed TCC and SCC. The
      primary form of bladder management was 44% urethral catheter for a mean of 33.3
      years, 48% external catheter for a mean of 37.4 years, and 8% intermittent
      catheterization for a mean of 24.5 years. Nineteen patients had a known method of
      cancer detection with 42% found on screening cystoscopy. CONCLUSIONS: The
      pathologic makeup of the tumors is similar to that reported earlier. Over 50% of
      patients diagnosed with bladder cancer in our population did not have an
      indwelling catheter. This suggests that the neurogenic bladder, not the
      indwelling catheter, may be the risk factor for bladder cancer. Urologists should
      consider diligent, long-term screening of all patients with SCI for bladder
      cancer and not just those with indwelling catheters.

PMID- 19752871
TI  - Identification of the most common problems in functioning of individuals with
      spinal cord injury using the International Classification of Functioning,
      Disability and Health.
AB  - STUDY DESIGN: Cross-sectional, multicenter study. OBJECTIVES: To identify the
      most common problems of individuals with spinal cord injury (SCI) in the early
      post-acute and the long-term context, respectively, using the International
      Classification of Functioning, Disability and Health (ICF) as a frame of
      reference. SETTING: International. METHODS: The functional problems of
      individuals with SCI were recorded using the 264 ICF categories on the second
      level of the classification. Prevalence of impairment was reported along with
      their 95% confidence intervals. Data were stratified by context. RESULTS: Sixteen
      study centers in 14 countries collected data of 489 individuals with SCI in the
      early post-acute context and 559 in the long-term context, respectively.
      Impairments in thirteen ICF categories assigned to Body functions and Body
      structures were more frequently reported in the long-term context, whereas
      limitations/restrictions in 34 ICF categories assigned to Activities and
      Participation were more frequently found in the early post-acute context. Eleven
      ICF categories from the component Environmental Factors were more frequently
      regarded as barriers, facilitators or both by individuals with SCI in the early
      post-acute context as compared with individuals with SCI in the long-term
      context. Only two environmental factors were more relevant for people with SCI in
      the long-term context than in the early post-acute context. CONCLUSION: The study
      identified a large variety of functional problems reflecting the complexity of
      SCI and indicated differences between the two contexts. The ICF has potential to
      provide a comprehensive framework for the description of functional health in
      individuals with SCI worldwide.

PMID- 19752872
TI  - Differences between subtotal corpectomy and laminoplasty for cervical spondylotic
      myelopathy.
AB  - OBJECTIVE: This study aimed to obtain guidelines for choosing between subtotal
      corpectomy (SC) and laminoplasty (LP) by analysing the surgical outcomes,
      radiological changes and problems associated with each surgical modality. STUDY
      DESIGN: A retrospective analysis of two interventional case series. SETTING:
      Department of Orthopaedic Surgery, Kagawa University, Japan. METHODS: Subjects
      comprised 34 patients who underwent SC and 49 patients who underwent LP. SC was
      performed by high-speed drilling to remove vertebral bodies. Autologous strut
      bone grafting was used. LP was performed as an expansive open-door LP. The level
      of decompression was from C3 to C7. Clinical evaluations included recovery rate
      (RR), frequency of C5 root palsy after surgery, re-operation and axial pain.
      Radiographic assessments included sagittal cervical alignment and bone union.
      RESULTS: Comparisons between the two groups showed no significant differences in
      age at surgery, preoperative factors, RR and frequency of C5 palsy. Progression
      of kyphotic changes, operation time and volumes of blood loss and blood
      transfusion were significantly greater in the SC (two- or three-level) group. Six
      patients in the SC group required additional surgery because of pseudoarthrosis,
      and four patients underwent re-operation because of adjacent level disc
      degeneration. In the LP group, the problem of elimination of postoperative axial
      symptoms remains to be solved. CONCLUSIONS: The merit of SC is the low frequency
      of axial symptoms. One-level SC can be considered to have similar degree of
      invasiveness as LP. Compared with SC, LP is more suitable for elderly patients
      with multilevel stenosis.

PMID- 19752873
TI  - Fat distribution in men of different waist girth, fitness level and exercise
      habit.
AB  - BACKGROUND: The risk of chronic disease is lower in obese men who are fit and
      active than obese men who are unfit and inactive. METHODS/OBJECTIVES: Magnetic
      resonance imaging and spectroscopy were used to assess total and regional adipose
      tissue in 13 men who were slim, fit and active (the slim-fit), in 12 men who were
      slim, unfit and inactive (the slim-unfit), in 13 men who were fat, fit and active
      (the fat-fit) and in 12 men who were fat, unfit and inactive (the fat-unfit), in
      order to investigate the hypothesis that visceral fat and liver fat are lower in
      the fat-fit than the fat-unfit. Waist girth was used to distinguish slim men (<
      or =90 cm) and fat men (> or =100 cm). Maximal oxygen consumption was used to
      identify fit men (above average for age) and unfit men (average or below for
      age). Fit men reported at least 60 min of vigorous aerobic activity per week and
      unfit men reported no regular moderate or vigorous activity in the last 2 years.
      RESULTS: Total fat was not significantly different in the slim-fit and the slim
      unfit, but the proportion of internal fat was significantly lower (P<0.05) and
      the proportion of visceral fat was almost significantly lower (P=0.06) in the
      slim-fit than all other groups. Total fat was not significantly different in the
      fat-fit and the fat-unfit, but visceral fat and liver fat were significantly
      lower in the fat-fit than the fat-unfit (P<0.01). Waist girth and years of
      exercise explained 84% of the variance in total fat, waist girth and maximal
      oxygen consumption explained 70% of the variance in visceral fat, and waist girth
      alone explained 25% of the variance in liver fat. CONCLUSION: Chronic disease
      risk may be lower because visceral fat and liver fat are lower in men who are
      fat, fit and active.

PMID- 19752874
TI  - Vasoreactivity is rapidly improved in obese subjects after gastric bypass
      surgery.
AB  - BACKGROUND: Obesity is associated with increased risk of cardiovascular disease.
      We investigated vasoreactivity in conduit and resistance arteries in morbidly
      obese subjects, and the effect of weight loss after gastric bypass surgery.
      METHODS: A total of 19 obese subjects (body mass index (BMI): 43.8+/-3.1 kg m(
      2), 75% female, mean age 41 years) were investigated before surgery and after 1
      and 12 months of surgery. Nineteen non-obese controls matched for age and gender
      were examined. Vasoreactivity was evaluated by ultrasound to measure flow
      mediated dilation (FMD, evaluating a conduit vessel) and pulse-wave analysis with
      terbutaline provocation (change in reflectance index (RI), evaluating resistance
      vessels). RESULTS: Before surgery, the obese showed a low change in RI (18+/-12
      vs 37+/-15% in controls, P=0.0001), but not significantly regarding FMD (7.9+/
      6.4 vs 8.9+/-5.4% in controls). Surgery resulted in a weight loss of 9% at 1
      month and 30% at 1 year. Change in RI markedly improved to 36+/-12% at 1 month
      (P=0.0001 vs baseline) and further to 44+/-11% at 1 year (P=0.014 vs 1 month).
      FMD did not change significantly. Heart rate and brachial artery diameter were
      reduced, with no significant change in blood pressure. The improvement in
      resistance vessel vasodilation, estimated as change in RI, was not correlated to
      changes in weight or measures of glucose and lipid metabolism. CONCLUSIONS: Obese
      patients showed impaired vasoreactivity in resistance arteries that was
      normalized already 1 month after gastric bypass surgery. The basis for this
      remarkable outcome, not significantly related to changes in body weight and
      metabolic variables, remains to be clarified.

PMID- 19752875
TI  - Thrift: a guide to thrifty genes, thrifty phenotypes and thrifty norms.
AB  - There is a growing interest in evolutionary models of human adiposity. Frequent
      reference has been made to 'thrifty genes' or 'thrifty phenotypes', referring to
      a variety of metabolic or behavioural traits that in one or the other way imply
      frugality in the expenditure or storage of energy. However, there is confusion
      over how the strategy of thrift has been incorporated into human biology. At the
      broadest level, humans represent a thrifty species relative to other mammals,
      indicating that metabolic adaptations had a crucial role in the emergence of the
      Homo lineage, in particular in buffering reproduction from ecological
      stochasticity. In contemporary humans, some variability in adiposity may be
      attributable to genotypes systematically favoured in certain ecological settings.
      Genetic variability is also present within populations, and may be considered bet
      hedging (distributing risk across offspring to increase parental fitness). Bet
      hedging is an alternative to genetic drift for accounting for genetic variability
      in the absence of strong selective pressures. Contrasting with genetic
      variability emerging over the long-term, thrifty phenotypes represent a response
      to short-term ecological variability. Physiological plasticity allows the
      emergence of variability across the life course in response to ecological cues
      experienced directly or by very recent ancestors. Finally, cultural norms or
      individual preferences allow voluntary behavioural manipulation of thrift in
      individuals. Overall, there is a range of factors and processes both favouring
      and opposing thrifty genes, which may reflect moderate bet hedging rather than
      systematic adaptation. Plasticity protects the genome from selective pressures by
      tailoring the organism to ongoing ecological conditions. The fact that obesity
      can occur in different individuals through different genotypes, life histories
      and behaviours indicates that different treatments are also likely to be
      required.

PMID- 19752876
TI  - Appropriate cutoff values of anthropometric variables to predict cardiovascular
      outcomes: 7.6 years follow-up in an Iranian population.
AB  - OBJECTIVE: To determine cutoff points of anthropometric variables for predicting
      incident cardiovascular disease (CVD) in Iranian adults. DESIGN: It is a
      population-based longitudinal study. SUBJECTS: A total of 1614 men and 2006
      women, aged > or =40 years, free of CVD at baseline were included in the study.
      MEASUREMENTS: Body mass index (BMI), waist circumference (WC), waist-to-hip ratio
      (WHR), waist-to-height ratio (WHtR) and cardiovascular risks were assessed.
      Incident CVD was ascertained over a median of 7.6 years follow-up. The adjusted
      hazard ratios (HRs) for CVD were calculated for 1 s.d. change in all obesity
      variables using Cox proportional hazards regression analysis. Receiver operator
      characteristic (ROC) curve analysis was used as the method of defining the points
      of the maximum sum of sensitivity and specificity (MAXss) of each variable as a
      predictor of CVD. RESULTS: We found 333 CVD events during follow-up. The risk
      factor-adjusted HRs were significant for all anthropometric variables in males
      and WHR in females and were 1.19, 1.24, 1.21 and 1.24 for BMI, WC, WHR and WHtR
      in males and 1.27 for WHR in females, respectively (all P<0.05). ROC analysis
      showed the highest area under curve (AUC) for WHR, WHtR and WC, followed by BMI
      in males and both genders aged< or =60 years. In females, WHR and WHtR had the
      highest AUC, followed by WC and BMI. Among those >60 years old, all the
      anthropometric variables showed same CVD predicting power. The cutoff values
      (MAXss) for CVD prediction in males and females were BMIs 26.95 and 29.19 kg m(
      2),WCs 94.5 and 94.5 cm, WHRs 0.95 and 0.90, and WHtR 0.55 and 0.62,
      respectively. CONCLUSION: There was no difference between central obesity
      variables in predicting CVD in males, whereas in females WHR and WHtR were more
      appropriate. The cutoff values of anthropometric variables were higher in the
      Iranian than in other Asian populations.

PMID- 19752877
TI  - The combined effects of overweight and smoking in late adolescence on subsequent
      disability pension: a nationwide cohort study.
AB  - BACKGROUND: Smoking and obesity are two of the most important risk factors for
      chronic disease today. Their combined effect on the risk of disability pension is
      not known. METHODS: A nationwide cohort of 45 920 Swedish men (18.7 + or - 0.5
      years) were followed for 38 years. The body mass index (BMI), based on measured
      height and weight, was used to define underweight (<18.5), normal weight (18.5
      24.9), overweight (25.0-29.9) and obesity (> or = 30.0). The hazard ratios (HRs)
      associated with BMI and smoking status at baseline for receiving disability
      pension were adjusted for socio-economic index (SEI), muscular strength,
      geographic region and place of residence. RESULTS: During 1.6 million person
      years, 4631 disability pensions and 2897 deaths occurred. After adjustment,
      overweight (HR 1.34, 95% CI 1.19-1.51) and obesity (HR 1.55, 1.18-2.05) were
      associated with an increased risk of disability pension, independent of smoking,
      whereas underweight (18.5; HR 1.07, 0.97-1.17) was not compared with normal
      weight. Similarly, smoking 1-10 (HR 1.37, 1.27-1.49) or >10 cigarettes per day
      (HR 2.01, 1.86-2.17) showed independent risk increases versus non-smoking.
      Although obese individuals smoking >10 daily cigarettes were at greatly increased
      risk (HR 2.98, 1.98-4.47), no evidence of interaction between the two risk
      factors could be detected. CONCLUSIONS: Both increased adiposity and smoking are
      strong and independent predictors of disability pension, but they do not act
      synergistically.

PMID- 19752878
TI  - Abnormal liver function test results are related to metabolic syndrome and BMI in
      Taiwanese adults without chronic hepatitis B or C.
AB  - BACKGROUND: Metabolic syndrome (MS) is considered a cause of abnormal deposition
      of fat into hepatocytes, which might be associated with hepatic steatosis or
      abnormal liver function. OBJECTIVE: The aim of this study was to explore the
      factors associated with MS and the relationship between MS and abnormal aspartate
      aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl
      transferase (GGT) levels in Taiwanese subjects without chronic hepatitis B (CHB)
      or C (CHC). SUBJECTS: We enrolled 2539 Taiwanese adults without CHB or CHC (age
      range: 16-88 years old) and investigated the factors related to MS using the NCEP
      ATP (National Cholesterol Education Program-Adult Treatment Panel) III criteria;
      body mass index (BMI) was measured using Asia-Pacific criteria. RESULTS: The
      prevalence rate of MS in Taiwanese adults without CHB or CHC was 16.9% using the
      modified ATP III criteria and 15.4% using the International Diabetes Federation
      criteria. Males had a significantly higher prevalence rate than females
      (P<0.001), and subjects with MS were significantly older and had significantly
      higher BMI values and AST, ALT and GGT levels (all P<0.001). In univariate
      analyses, the abnormality of liver function test results were related to gender,
      level of fasting sugar, systolic blood pressure, triglyceride, high-density
      lipoprotein, BMI and MS (all P<0.05). Multivariate analysis showed that the male
      gender, a higher BMI value and MS were related to abnormal liver function test
      results. The cutoff value for ALT in relation to MS is 31 IU l(-1) for male and
      18 IU l(-1) for female. CONCLUSION: The prevalence of MS in Taiwanese adults
      without hepatitis B or C was found to be high, and MS and BMI were identified as
      being related to abnormal liver function test results in these adults.

PMID- 19752879
TI  - Satiety and amino-acid profile in overweight women after a new treatment using a
      natural plant extract sublingual spray formulation.
AB  - OBJECTIVE: To test the effect on satiety of a formulation comprising plant
      extracts naturally containing 5-hydroxytryptophan, delivered as sublingual spray
      (5HTP-Nat Exts), administered five times a day for 2 months. DESIGN: Two-month,
      randomized, double-blind, placebo-controlled trial. SUBJECTS: A total of 27
      healthy, adult overweight women were randomly assigned to the treatment (14) or
      the placebo group (13). MEASUREMENTS: Visual analog scales were used to assess
      appetite sensations every day. Moreover, the study evaluated the bioavailability
      of 5-hydroxytryptophan following sublingual delivery over 8 weeks, by comparing
      24-h urinary excretion of 5-hydroxy-3-indoleacetic acid (5-HIAA), determined at
      baseline and after 2 months. Other secondary end points of the study were to
      compare body composition, depressive symptoms, severity of binge eating and
      quality of life. Finally, the study tested whether a single administration of
      5HTP-Nat Exts in fasting state has an effect on amino-acid profile and on
      appetite ratings and whether 5HTP-Nat Exts administered before a fixed test meal
      has any effect on satiety. RESULTS: The group using the 5HTP-Nat Exts experienced
      a significantly greater increase in their sensation of satiety over an 8-week
      timeframe and in fasting state following administration of 5HTP-Nat Exts than the
      placebo group did (AUC=305.2 (52.8) vs 236.6 (59.4), mean difference -68.7 (95%
      confidence interval (CI) -116.2 to -21.2), P=0.007; mean difference in Haber
      score change 2.5 (95% CI 0.62-3.12, P=0.007)). A difference was observed between
      the groups for the mean change in 5-HIAA. All the amino acids evaluated after a
      single administration of 5HTP-Nat Exts were found to be similar. Differences were
      found for the mean change in body mass index, skinfold thicknesses and hip
      circumference. The other parameters were found to be similar. CONCLUSION: All
      these findings suggest that 5HTP-Nat Exts may be safely used to treat the problem
      of appetite control in overweight women during a weight loss program.

PMID- 19752880
TI  - Association between nocturnal blood pressure dipping and insulin metabolism in
      obese adolescents.
AB  - OBJECTIVE: The purpose of this study was to analyze the relationship between
      insulin-glucose metabolism, nocturnal blood pressure (BP) dipping and cardiac
      left ventricular mass (LVM) in obese adolescents without diabetes. METHODS: A
      cohort of 206 obese adolescents (mean age 15.4 years (s.d. 1.6), mean body mass
      index (BMI) 38 kg m(-2) (s.d. 5.8), 53% girls) under clinical care were included
      in the study. Body fat was assessed by dual X-ray absorptiometry (DEXA). Blood
      samples were drawn for analyses of fasting insulin (fS-insulin), fasting glucose
      and glycosylated hemoglobin Alc. Homeostatic model assessment index (HOMA index)
      was calculated. Insulin sensitivity and acute insulin response (AIR) were
      calculated from the performed frequently sampled intravenous glucose tolerance
      test. An ambulatory BP measurement was performed and 24 h daytime and nighttime
      values were calculated. Non-dipping was defined as a nocturnal BP reduction of
      <10%. Ultrasound was used to measure heart LVM and LVM index (LVMI) was
      calculated (LVM x height(-2.7)). RESULTS: Systolic non-dipping was present in 50%
      (n=103) of the subjects. Systolic and diastolic dipping was negatively associated
      with measures of insulin metabolism (HOMA index, fS-insulin and AIR). These
      associations were present independently of gender, age, daytime BP or body mass
      index standard deviation score. Dipping (P=0.7-0.9) or measures of insulin
      glucose metabolism (P=0.3-1.0) were not associated with LVMI in this population.
      CONCLUSION: Non-dipping is common among obese adolescents. We found a negative
      association between nocturnal BP fall (dipping) and measures of insulin
      metabolism independently of the degree of obesity or daytime BP level among
      severely obese, non-diabetic adolescents without diagnosed hypertension. Our
      findings suggest the importance of keeping the insulin levels under observation
      even in allegedly healthy obese adolescents in clinical care, as a part of the
      prevention of morbidity associated with obesity.

PMID- 19752881
TI  - The genetic and environmental influences on childhood obesity: a systematic
      review of twin and adoption studies.
AB  - In this systematic review, we aimed to collect together all previous twin and
      adoption studies on childhood and adolescent obesity up to the age of 18 years.
      Using several sources, we identified nine twin and five adoption studies; all of
      these studies had used relative weight as an indicator of obesity. Except the two
      twin studies from the Korean population, all studies represented Caucasian
      populations. In a meta-analysis of these twin studies, we found that genetic
      factors had a strong effect on the variation of body mass index (BMI) at all
      ages. The common environmental factors showed a substantial effect in mid
      childhood, but this effect disappeared at adolescence. Adoption studies supported
      the role of family environment in childhood obesity as correlations were found
      between adoptees and adoptive parents; however, correlations were substantially
      stronger between parents and their biological offspring, further supporting the
      importance of genetic factors. In the future, more studies implementing genetic
      and environmental measures into twin models are needed as they allow estimation
      of the proportion of total genetic variation explained by candidate genes and
      analyses of gene-environment interactions. More studies of genetic architecture
      in non-Caucasian populations, of gene-environment interactions, and of body
      composition and body fat distribution are needed.

PMID- 19752882
TI  - Association of calpain-10 gene polymorphism and posttransplant diabetes mellitus
      in kidney transplant patients medicated with tacrolimus.
AB  - New-onset, posttransplant diabetes mellitus (PTDM) has a high incidence after
      kidney transplantation in patients medicated with tacrolimus, and may adversely
      affect the patient and graft survival. The pathophysiology of PTDM closely mimics
      that of type II diabetes mellitus (T2DM). One of possible genetic factors
      predisposing to PTDM might be polymorphism in calpain-10 gene (CAPN10),
      previously associated with increased risk of T2DM in general population.
      Therefore, the present study was aimed at evaluation of CAPN10 gene polymorphisms
      in PTDM in kidney transplant patients medicated with tacrolimus. A total of 214
      nondiabetic kidney transplant patients medicated with tacrolimus (56 patients
      with PTDM and 158 patients without PTDM were genotyped for the presence of CAPN10
      gene variants (SNP-43: rs3792267:G>A, SNP-19: rs3842570 ins/del and SNP-63:
      rs5030952:C>T) using PCR-based assays. Frequency of SNP-63 minor allele was
      slightly increased in PTDM patients (P=0.056), and an association of SNP-63
      heterozygosity and the risk of PTDM (odds ratios (OR)=2.45, P=0.023) was
      observed. An increased odds for PTDM development in patients carrying 1-1-2
      haplotype (rs3792267:G-rs3842570:ins-rs5030952:T) compared to noncarriers was
      also noted (OR=2.35, P=0.026). Patients' higher body mass index and SNP-63 minor
      T allele carrier status were identified as independent PTDM risk factors,
      confirmed by multivariate regression analysis. This is the first study of CAPN10
      polymorphism in relation to PTDM risk. However, the application of SNP-63
      (rs5030952:C>T) as a marker of PTDM should be verified by further independent
      studies.

PMID- 19752883
TI  - Transcriptome analysis of nicotine-exposed cells from the brainstem of neonate
      spontaneously hypertensive and Wistar Kyoto rats.
AB  - In this study, the effects of nicotine on global gene expression of cultured
      cells from the brainstem of spontaneously hypertensive rat (SHR) and normotensive
      Wistar Kyoto (WKY) rats were evaluated using whole-genome oligoarrays. We found
      that nicotine may act differentially on the gene expression profiles of SHR and
      WKY. The influence of strain was present in 321 genes that were differentially
      expressed in SHR as compared with WKY brainstem cells independently of the
      nicotine treatment. A total of 146 genes had their expression altered in both
      strains after nicotine exposure. Interaction between nicotine treatment and the
      strain was observed to affect the expression of 229 genes that participate in
      cellular pathways related to neurotransmitter secretion, intracellular
      trafficking and cell communication, and are possibly involved in the phenotypic
      differentiation between SHR and WKY rats, including hypertension. Further
      characterization of their function in hypertension development is warranted.

PMID- 19752884
TI  - MDR1 (C3435T) polymorphism: relation to the risk of breast cancer and therapeutic
      outcome.
AB  - P-glycoprotein (PGP), the product of the MDR1 gene, is a transmembrane active
      efflux pump for a variety of carcinogens and cytostatics. It has been suggested
      that MDR1 polymorphisms contribute to the variability in cancer risk and
      therapeutic outcome. We examined the relevance of C3435T polymorphism in relation
      to breast cancer susceptibility, clinical and pathological characteristics of
      breast carcinoma, the therapeutic response and hematologic toxicities after
      anthracycline-based chemotherapy. A significant association between allele
      frequencies and histological type, stage and histological grade was observed
      (P=0.024, 0.014, 0.006, respectively, chi(2)-test or Fisher's exact test). We
      also found significantly higher (P=0.019, chi(2)-test) T allele frequency in
      breast cancer patients (n=221) than in controls (n=113). A significantly enhanced
      therapeutic outcome after neoadjuvant therapy (n=38; P=0.021, Fisher's exact
      test) and longer time to progression after anthracycline-based chemotherapy
      (n=102; P=0.049, log-rank test) were observed in CC homozygotes. However, no
      significant association between hematologic toxicities and C3435T polymorphism
      was detectable.

PMID- 19752885
TI  - Demonstrating the pharmacogenetic effects of angiotensin-converting enzyme
      inhibitors on long-term prognosis of diastolic heart failure.
AB  - The objective of this study was to evaluate the effects of angiotensin-converting
      enzyme (ACE) inhibitors and pharmacogenetic interaction on the survival of the
      patients with diastolic heart failure (DHF). A total of 285 subjects with DHF
      confirmed by echocardiography were recruited in the period between 1995 and 2003.
      Baseline characteristics (age, sex, prior history, medication, and
      echocardiographic findings) and genetic polymorphisms (ACE gene
      insertion/deletion (I/D) polymorphism; T174M, M235T, G-6A, A-20C, G-152A, and G
      217A polymorphisms of the angiotensinogen (AGT) gene; and A1166C polymorphisms of
      the angiotensin II type I receptor (AT1R)) were collected and matched (by
      propensity score) in those who received and those who did not receive ACE
      inhibitors. The patients were followed up to 10 years. Kaplan-Meier curves and
      Cox regression models were used to demonstrate the survival trend. The 85
      patients who received ACE inhibitors and the other 85 patients who did not were
      found to have comparable baseline characteristics and polymorphism distribution.
      Prescription of ACE inhibitors was associated with a significant decrease in
      overall mortality (hazard ratio (HR), 0.45; 95% confidence interval (CI), 0.24
      0.83; P=0.01), and a lower rate of cardiovascular events at 4000 days (HR, 0.53;
      95% CI, 0.32-0.90; P=0.02). In addition, ACE I/D gene D allele was associated
      with higher overall mortality as compared with the I allele (HR, 2.04; P=0.003).
      This effect was diminished in those who received ACE inhibitors. The use of ACE
      inhibitor was associated with a significant decrease in long-term mortality and
      cardiovascular events in the patients with DHF. Genetic variants in the renin
      angiotensin system genes were also associated, but their effects could be
      modified by the use of ACE inhibitors.

PMID- 19752886
TI  - Prostate cancer detection using an extended prostate biopsy schema in combination
      with additional targeted cores from suspicious images in conventional and
      functional endorectal magnetic resonance imaging of the prostate.
AB  - The purpose of this study is to report our method in detecting prostate cancer
      (PCa) using an 18-core transrectal ultrasound (TRUS) prostate biopsy (PB) schema,
      in combination with additional targeted cores from suspicious images in
      conventional (e-cMRI) and functional (e-fMRI) endorectal magnetic resonance
      imaging (e-MRI) of the prostate. From 2004 to 2008, 260 consecutive patients with
      a clinical suspicion of PCa underwent PB and were prospectively studied. e-cMRI
      and e-fMRI was performed in all patients before PB. The patients were divided
      into two groups (A and B) according to the results of their radiological findings
      (group A=suspicious findings, group B=non-suspicious findings). After the images
      were processed, an 18-core TRUS-guided PB was performed. When a patient exhibited
      a suspicious site on e-cMRI and e-fMRI images, three additional targeted PBs were
      obtained from that site. In group A, 17.5% of PCa was detected by the 18-core PB
      and 56.5% of PCa was detected by the targeted cores. The overall PCa detection
      rate (18+targeted cores) was 73.9%. The overall specificity was 73.9%. In group
      B, overall false-positive detection rate reached 19.2%, with the overall
      sensitivity being 80.8%. The method described above is not only practical but
      also a promising modality in PCa detection. As seen, PCa was optimally detected
      when combining the 18-core and targeted-core PB schema together. Non-suspicious
      images do not rule out the probability of PCa, thus justifying a PB in these
      patients as well.

PMID- 19752887
TI  - Dual function of Arabidopsis ATAF1 in abiotic and biotic stress responses.
AB  - NAC family genes encode plant-specific transcription factors involved in diverse
      biological processes. In this study, the Arabidopsis NAC gene ATAF1 was found to
      be induced by drought, high-salinity, abscisic acid (ABA), methyl jasmonate,
      mechanical wounding, and Botrytis cinerea infection. Significant induction of
      ATAF1 was found in an ABA-deficient mutant aba2 subjected to drought or high
      salinity, revealing an ABA-independent mechanism of expression. Arabidopsis ATAF1
      overexpression lines displayed many altered phenotypes, including dwarfism and
      short primary roots. Furthermore, in vivo experiments indicate that ATAF1 is a
      bona fide regulator modulating plant responses to many abiotic stresses and
      necrotrophic-pathogen infection. Overexpression of ATAF1 in Arabidopsis increased
      plant sensitivity to ABA, salt, and oxidative stresses. Especially, ATAF1
      overexpression plants, but not mutant lines, showed remarkably enhanced plant
      tolerance to drought. Additionally, ATAF1 overexpression enhanced plant
      susceptibility to the necrotrophic pathogen B. cinerea, but did not alter disease
      symptoms caused by avirulent or virulent strains of P. syringae pv tomato DC3000.
      Transgenic plants overexpressing ATAF1 were hypersensitive to oxidative stress,
      suggesting that reactive oxygen intermediates may be related to ATAF1-mediated
      signaling in response to both pathogen and abiotic stresses.

PMID- 19752888
TI  - A transcription factor with a bHLH domain regulates root hair development in
      rice.

PMID- 19752889
TI  - Compact scanning soft-x-ray microscope using a laser-produced plasma source and
      normal-incidence multilayer mirrors.
AB  - We have constructed a scanning soft-x-ray microscope that uses a laser-produced
      plasma as the soft-x-ray source and normal-incidence multilayer-coated mirrors in
      a Schwarzschild configuration as the focusing optics. The microscope operates at
      a wavelength of 14 nm, has a spatial resolution of 0.5 microm, and has a soft-x
      ray photon flux through the focus of 10(4)-10(5) sec(-1) when operated with only
      170 mW of average laser power. The microscope is compact; the complete system,
      including the laser, fits on a single optical table.

PMID- 19752890
TI  - Absolute optical ranging with 200-nm resolution.
AB  - Absolute optical ranging has been demonstrated by wavelength-multiplexed
      interferometry with a range resolution of 200 nm, well below the single
      wavelength ambiguity. Two current- and temperature-tunable GaAlAs laser diodes
      (850 nm) provide an equivalent wavelength below 100 microm and a resolution of
      less than 200 nm. The achievement of such resolution provides the means for
      combining single- and multiple-wavelength interferometric measurements to achieve
      unambiguous distance measurement with nanometer resolution. The ranging system is
      also used to profile unambiguously an integrated circuit structure with a 2.5
      microm surface topography.

PMID- 19752891
TI  - Optimum encoding of binary phase-only filters with a simulated annealing
      algorithm.
AB  - A simulated annealing algorithm is introduced to encode binary phase-only filters
      optimally for image recognition. Similar patterns that cannot be distinguished
      with conventional filter encoding methods are clearly distinguished with the
      optimized filter. The computational requirements for optimizing the filter are
      not excessive.

PMID- 19752892
TI  - Scattering of incident KrF laser radiation resulting from the laser-induced
      breakdown of H(2)O droplets.
AB  - The time history of elastically scattered incident radiation (ESIR) is presented
      for 60-microm-diameter water droplets irradiated by KrF (lambda = 248 nm) laser
      pulses with power densities in the range of 1-200 GW/cm(2). The ESIR shows a
      distinct two-peak structure that is dependent on the incident irradiance. The
      time delay between the arrival of the incident pulse and the first local minimum
      in the ESIR varied from 7 nsec at 200 GW/cm(2) to 21 nsec at 5 GW/cm(2). The time
      between incident pulse arrival and the first peak in the ESIR showed a similar
      irradiance dependence, with delays ranging from 4 to 12 nsec. Images of droplet
      breakup and the average velocities of ejected material are presented for times
      between 0 and 1000 nsec after the arrival of 3-GW/cm(2) laser pulses.

PMID- 19752893
TI  - Ultrashort-pulse multichannel infrared spectroscopy using broadband frequency
      conversion in LiIO(3).
AB  - A simple probing method for obtaining broadband multichannel infrared spectra
      with picosecond or higher time resolution is described. Spectrally broad infrared
      pulses are produced by difference frequency mixing in LiIO(3) between the second
      harmonic of a Nd(+3):YAG laser and the broadband output of a synchronously pumped
      dye laser. After sample absorption the infrared pulse is upconverted by a second
      LiIO(3) crystal, which yields a visible pulse that is dispersed on a multichannel
      vidicon detector to obtain transient spectra of 4-cm(-1) FWHM resolution.

PMID- 19752894
TI  - Laser measurement of the (16)O-(18)O isotope shift at optical frequencies.
AB  - We demonstrate the full resolution of isotope shifts in atomic O by means of sub
      Doppler laser optogalvanic spectroscopy of (18)O-enriched samples. The
      measurements are performed to within a few percent accuracy on four transitions
      ranging from 605 to 646 nm and involving excited states. Previously published
      values from conventional spectroscopy are either unavailable or are one order of
      magnitude less accurate and in marginal agreement with our data.

PMID- 19752895
TI  - Picosecond optical parametric oscillator pumped by temporally compressed pulses
      from a Q-switched, mode-locked, cw-pumped Nd:YAG laser.
AB  - Using, for the first time to our knowledge, the frequency-doubled temporally
      compressed pulses from a cw-pumped, Q-switched, mode-locked Nd:YAG laser to pump
      a parametric oscillator based on temperature-tuned barium sodium niobate, we
      generated resolution-limited pulses of 3.5 psec, tunable from 0.95 to 1.2 microm,
      with an energy efficiency of up to 13% at Q-switched rates of up to 3 kHz.

PMID- 19752896
TI  - Highly efficient visible urea optical parametric oscillator pumped by a XeCl
      excimer laser.
AB  - We report the successful operation of a visible optical parametric oscillator
      (OPO) that uses urea as the nonlinear medium and is pumped in the near field of
      an injection-seeded pulsed XeCl excimer laser operating at 308 nm. The OPO can
      generate continuously tunable radiation from 537 to 720 nm with a single set of
      dichroic mirrors, and conversion efficiencies as high as 37% have been achieved
      in a 15-mm-long crystal at 90 degrees phase matching. The influence of crystal
      double refraction (and hence beam walk-off) on the conversion efficiency across
      the OPO tuning range is discussed, and some oscillator parameters, including
      spectral linewidth and temporal behavior, are characterized.

PMID- 19752897
TI  - Two-dimensional phase-conjugate imaging of atomic distributions in flames by
      degenerate four-wave mixing.
AB  - We report the demonstration of a technique using resonant degenerate four-wave
      mixing to produce high-resolution, background-free images of atomic distributions
      in flames. Comparison with laser-induced-fluorescence methods and applications of
      the method to species of interest in combustion are briefly discussed.

PMID- 19752898
TI  - Theory for the temperature rise in optically bistable GaAs/AlGaAs etalons
      including diffraction, heat conduction, and carrier diffusion.
AB  - We report on a realistic model for optically bistable GaAs/AlGaAs Fabry-Perot
      etalons. The model incorporates diffraction, carrier diffusion, and heat
      conduction, taking all the layers of the structure into account. For the optical
      nonlinearity the carrier density and temperature-dependent plasma theory is used.
      Devices with less than a 1-K temperature rise should be possible to design.

PMID- 19752899
TI  - Linear phase-conjugate oscillator employing a photorefractive crystal.
AB  - Using Yeh's analytic method [J. Opt. Soc. Am. A 2, 727 (1985)] we derive the
      oscillation conditions of a linear phaseconjugate oscillator consisting of a
      photorefractive crystal and two conventional mirrors. For the special case of a
      90-rad phase shift, the threshold oscillation conditions of the linear phase
      conjugate oscillator are derived as a function of cavity length. The results
      indicate that, unlike in the case of a phase-conjugate oscillator employing a
      Kerr-like material, in which oscillation can occur for any cavity length,
      oscillation can occur in this case only for specified ranges of the cavity length
      determined by the coupling strength. We also show that for larger coupling
      strengths oscillation can occur over wider ranges of the cavity length.

PMID- 19752901
TI  - Highly sensitive polarization-controlled optical switching with a photorefractive
      double phase conjugator.
AB  - Highly sensitive polarization-controlled optical switching is demonstrated
      experimentally through a photorefractive BaTiO(3) double-phase-conjugate mirror.
      A theoretical explanation is developed, and possible applications are mentioned.

PMID- 19752900
TI  - Grating-encoded multichannel photorefractive incoherent-to-coherent optical
      conversion.
AB  - A dynamic multichannel incoherent-to-coherent optical converter based on the
      photorefractive effect of SBN:Ce is described. A number of grating-encoded input
      images, illuminated by incoherent light, are projected onto the crystal to yield
      photoinduced phase gratings. Coherent positive replicas of these images are
      simultaneously reconstructed by a coherent read beam. A simple theoretical
      description of this converter and corresponding experimental results are
      presented.

PMID- 19752902
TI  - Self-phase modulation in multimode optical fibers produced by moderately high
      powered picosecond pulses.
AB  - The spectral distributions of 8-psec ultrashort laser pulses propagating through
      multimode glass fibers were measured and compared with those of single-mode
      fibers at comparable intensities. In multimode optical fibers the spectral
      broadening arising from self-phase modulation was found to be asymmetric to the
      Stokes side owing to modal dispersion.

PMID- 19752903
TI  - Evaluation of performance parameters of single-mode all-fiber Brillouin ring
      lasers.
AB  - An analytical theory of the operation of all-fiber Brillouin ring lasers that
      accounts for pump depletion is presented. Expressions for stimulated Brillouin
      scattering lasing threshold power, output Stokes power, and conversion efficiency
      are derived. It is shown that the fiber cavity detunes from its resonant value
      owing to the buildup of the counterpropagating Stokes wave, which can be a
      limitation in the performance of all-fiber resonator systems. The application of
      the theory is in the design and optimization of performance parameters of devices
      using all-fiber ring resonators, particularly Brillouin lasers and gyroscopes.

PMID- 19752904
TI  - Theoretical evaluation of intermodulation distortion due to four-wave mixing in
      optical fibers for coherent phase-shift-keying-frequency-division-multiplexing
      transmission.
AB  - Intermodulation distortion due to four-wave mixing in optical fibers is
      theoretically evaluated for coherent phaseshift-keying-frequency-division
      multiplexing transmission, and the demodulated signal deviation in differential
      phase-shift-keying detection is calculated. The intermodulation distortion is
      characterized by the probability distribution of the signal deviation.

PMID- 19752905
TI  - Magneto-optic current sensor using a helical-fiber Fabry-Perot resonator.
AB  - The concept of a magneto-optic current sensor that employs a fiber-optic Fabry
      Perot resonator shaped into a single-turn helix is presented. The helical shape
      permits construction of a compact device that has the required polarization
      properties. Compared with a single-pass sensor, a large increase in sensitivity
      is obtained as a result of the finesse of the resonator. Experimental results
      confirm the theory and show that for a finesse of F = 6 the sensitivity is four
      times larger than for a single-pass sensor.

PMID- 19752906
TI  - Fiber-optic sensor using a tandem combination of a multimode fiber and a self
      pumped phase conjugator.
AB  - An interferometric sensing scheme using a multimode fiber and a self-pumped phase
      conjugator is proposed. The self-pumped phase conjugator corrects the distortion
      due to mode scrambling in the fiber and responds to any uniform optical phase
      change caused by environmental factors. A temperature sensor based on the
      proposed scheme is used to demonstrate the feasibility of the scheme.

PMID- 19752907
TI  - Modes in chirowaveguides.
AB  - We introduce here a new class of waveguides, chirowaveguides, which exhibit some
      novel and unique properties owing to electromagnetic chirality. These waveguides
      consist of cylindrical waveguides containing chiral, or optically active,
      materials. Owing to the optical activity of the material inside the waveguide,
      several unique and novel features are associated with this type of guided-wave
      structure. It is shown that these waveguides cannot support individual TE, TM, or
      TEM modes and that they exhibit mode bifurcation in hybrid modes. As an
      illustrative example the parallel-plate chirowaveguide is analyzed, and the
      corresponding dispersion relations and Brillouin diagrams are obtained. Some of
      the novel applications of chirowaveguides to integrated-optical devices and
      optical communications systems are presented.

PMID- 19752908
TI  - Potential optical gain with two crossed Fabry-Perot resonators: the influence of
      absorption.
AB  - A crossed resonator Fabry-Perot device is analyzed for a collection of nonlinear
      optical materials, including bulk semiconductors, the intraband transition in a
      multiple quantum well, organic polymers, and semiconductor-doped glasses, to
      determine its suitability for photonic switching and optical computing. We find
      that as an optical switch the crossed resonator offers a considerably steeper
      threshold and somewhat flatter wings than a single Fabry-Perot resonator and that
      to achieve optical gain the absorption per pass must be lower than 0.05.

PMID- 19752909
TI  - Adaptive optical processors.
AB  - There are two different approaches for improving the accuracy of analog optical
      associative processors: postprocessing with a bimodal system and preprocessing
      with a preconditioner. These two approaches can be combined to develop an
      adaptive optical multiprocessor that can adjust the computational steps depending
      on the data and produce solutions of linear algebra problems with a specified
      accuracy in a given amount of time.

PMID- 19752910
TI  - Laser-induced fluorescence of the Zn(2) excimer.
AB  - Pump-and-probe methods of laser spectroscopy with time resolution were used to
      study fluorescence and excitation spectra arising from transitions involving the
      (1) product operator(u)(4(1)P), (3) product operator(g)(4(3)P), and
      X(1)Sigma(+)(g)(4(1)S) states for the Zn(2) excimer. An analysis of the
      vibrational bands yielded vibrational constants, relative energies, and relative
      internuclear separations for the (1) product operator(u) and (3) product
      operator(g) states.

PMID- 19752911
TI  - Frequency-stabilized laser-diode-pumped Nd:YAG laser.
AB  - We describe a frequency-stabilized diode-pumped Nd:YAG laser that is actively
      frequency stabilized relative to a reference Fabry-Perot cavity using the Pound
      Drever technique. We describe the servo loop and the measurement of its noise and
      gain performance and demonstrate its ability to reduce the laser frequency noise
      close to the shotnoise limit of 12.5 mHz/ radicalHz. This corresponds to a
      linewidth of approximately 1 mHz, well below the Schawlow-Townes limit of 0.13 Hz
      that applies for a free-running laser.

PMID- 19752912
TI  - Continuous-wave laser operation of chromium-doped forsterite.
AB  - Room-temperature continuous-wave laser action in chromium-activated forsterite
      (Cr:Mg(2)SiO(4)) has been achieved for longitudinal pumping in a nearly
      concentric cavity by the 1064-nm radiation from a cw Nd:YAG laser. The laser
      emission is centered at 1244 nm and has a spectral bandwidth of 12 nm. An output
      power slope efficiency of 6.8% is measured. The effective emission cross section
      is estimated to be ~1.1 x 10(-19) cm(2).

PMID- 19752913
TI  - Nonlinear optical interaction in semiconductor lasers due to population
      pulsations.
AB  - Population pulsations are demonstrated as a basic mechanism for nonlinear optical
      interaction in a semiconductor laser by detecting the optical beat frequency in
      the noise spectrum of the injection current.

PMID- 19752914
TI  - Frequency-modulated Nd:YAG microchip lasers.
AB  - Tunable, single-frequency, Nd:YAG microchip lasers have been piezoelectrically
      frequency modulated over several hundred megahertz at rates from dc to 25 MHz.

PMID- 19752915
TI  - Additive-pulse mode-locked NaCl:OH(-) laser.
AB  - The operation of an additive-pulse mode-locked NaCl:OH(-) color-center laser is
      described. Stable output pulses as short as 75 fsec have been obtained. The laser
      is tunable from 1.51 to 1.65microm, with 300 mW of average output power at 1.6
      microm.

PMID- 19752916
TI  - Efficient population inversion in excimer states by supersonic expansion of
      discharge plasmas.
AB  - Laser emission at 126 nm has been obtained from excimers of Ar(2) excited
      electrically in a nozzle discharge followed by supersonic expansion. The direct
      measurement of light amplification with a tunable VUV probe leads to a gain of >3
      cm(-1). This high gain arises from efficient population inversion of low
      vibrational and rotational levels of the excimer state brought about by the
      supersonic expansion and cooling of the discharge plasma.

PMID- 19752917
TI  - Coherence theoretic algorithm to determine the transverse-mode structure of
      lasers.
AB  - We introduce an algorithm to determine the relative modal weights of a laser beam
      with Hermite-Gaussian modes. The method is based on coherence theory of stable
      resonator modes in the space-frequency domain. Numerical simulations are
      presented that show that the algorithm is not sensitive to moderate levels of
      noise.

PMID- 19752918
TI  - Temporal imaging with a time lens.
AB  - We extend the well-known analogy between the problems of paraxial diffraction in
      space and dispersion in time to optical pulse compression and propose a time
      domain analog to spatial imaging that allows for the distortionless expansion or
      compression of optical power waveforms. We call this new concept temporal imaging
      and derive equivalent expressions for the focal length and the f-number of a time
      lens and the magnification of an imaging system. It should now become possible,
      with a temporal microscope, to expand ultrafast optical phenomena to a time scale
      that is accessible to conventional high-speed photodiodes.

PMID- 19752919
TI  - Subpicosecond accumulated photon echoes using a continuous-wave multimode diode
      laser.
AB  - Subpicosecond accumulated photon echoes have been observed in 1,3,3,1',3',3'
      hexamethyl-2,2'-indotricarbocyanine iodide embedded in polyvinyl alcohol at 10 K
      by using a cw multimode diode laser. The temporal resolution of this measurement
      is determined by the width of the overall spectral envelope of the diode laser.
      The dephasing time of 40 psec derived by the echo decay curve is in good
      agreement with the persistent hole width.

PMID- 19752920
TI  - Reshaping of infrared picosecond pulses after passage through atmospheric CO(2).
AB  - Substantial pulse deformation of picosecond pulses at lambda = 4.3 microm in air
      is observed, resulting from strong coherent interaction with 10 nearly
      equidistant rovibrational lines of the asymmetric nu(3) stretching mode of CO(2).
      The coherent reemissions of the different states interfere constructively after
      times of Deltat = 19 and 38 psec as expected from the frequency separation of two
      neighboring states of Deltanu = 1.75 cm(-1) according to the equation Deltat = (c
      x Deltanu )(-1).

PMID- 19752921
TI  - Experimental observation of thermal-blooming phase-compensation instability.
AB  - We have made the first experimental observations to our knowledge of thermal
      blooming phase-compensation instability. We identified the instability by
      impressing a spatial intensity modulation on the laser beam and watching this
      modulation grow as thermal-blooming compensation was performed with a 69-channel
      phaseconjugate adaptive-optics system.

PMID- 19752922
TI  - Two-wave mixing and phase conjugation at 830 nm in BaTiO(3).
AB  - We report two-wave mixing and self-pumped phase-conjugation measurements for
      GaAlAs laser-diode radiation at 830 nm in BaTiO(3). At 11 degrees C, two-wave
      mixing gain coefficients as large as 18 cm(-1) and response times of the order of
      1 min have been observed by using an optimized mixing geometry. Phase-conjugate
      reflectivities as large as 56% with 10-sec response times have also been measured
      using BaTiO(3) in a passive ring conjugator when the source laser is optically
      isolated from the conjugator. These results represent significant improvements
      over corresponding values previously reported.

PMID- 19752923
TI  - Fiber polarization-rotation switch based on modulation instability.
AB  - We demonstrate an active fiber polarization-rotation switch based on modulation
      instability operating near 1.5 microm that exhibits contrast ratios of up to 40:1
      and small-signal gains of up to 40 dB. Modulation instability generates upper and
      lower sideband frequencies with different states of polarization from the pump at
      the fiber output. The high contrast ratio is achieved in part because intensity
      fluctuations with the pump alone do not lead to an output from the device.

PMID- 19752925
TI  - Array illuminator using grating couplers.
AB  - An integrated-optical array illuminator is proposed, and the principle of
      generating multiple beamlets by using grating couplers is described. Preliminary
      experiments are performed to demonstrate the validity of the principle.

PMID- 19752924
TI  - True single-polarization design for bow-tie optical fibers.
AB  - Based on a stress analysis of bow-tie optical fibers, a mechanism for true single
      mode single-polarization operation of bow-tie optical fibers is presented. The y
      polarized mode can have a loss of the order of 10 dB/m, while the x-polarized
      mode remains well confined and without loss.

PMID- 19752926
TI  - Fundamental limit on accuracy in interferometry.
AB  - We derive a golden rule to evaluate the limit on fringe resolution. The rule,
      which is derived from basic principles, takes into consideration the existence of
      mechanical vibration. We show that conventional interferometer systems are
      limited by the available vibration-isolation tables to approximately 1/1000 of a
      fringe. In principle, moire deflectometry can yield a much better signal-to-noise
      ratio.

PMID- 19752927
TI  - Fresnel lens-encoded binary phase-only filters for optical pattern recognition.
AB  - We describe a technique for reducing false signals from optical correlators using
      binary phase-only filters (BPOF's). Since the impulse-response function of the
      BPOF contains both the target object and the inverted version of it, the output
      consists of the correlation of the input object with both of these objects. In
      our research a Fresnel phase plate lens is encoded onto the BPOF. As a result the
      correlation with the desired target is on a converging beam, and the correlation
      with the undesired inverted image of the target is on a diverging beam.
      Experimental results show that these filters reject inverted input objects.

PMID- 19752928
TI  - Simple spectral method for solving propagation problems in cylindrical geometry
      with fast Fourier transforms.
AB  - We describe a spectral method for solving the paraxial wave equation in
      cylindrical geometry that is based on expansion of the exponential evolution
      operator in a Taylor series and use of fast Fourier transforms to evaluate
      derivatives. A fourth-order expansion gives excellent agreement with a two
      transverse-dimensional split-operator calculation at a fraction of the cost in
      computation time per z step and at a considerable savings in storage.

PMID- 19752929
TI  - Gain measurements at 18.22 nm in C VI generated by a Nd:glass laser.
AB  - We present recent gain measurements in C VI at 18.22 nm for a soft-x-ray
      amplifier produced by a line-focused glass laser (1.053 microm) on a solid carbon
      target. The maximum gain measured was 8 +/- 2 cm(-1) in the recombining plasma
      column, with additional radiation cooling, with additional radiation cooling by
      iron impurities.

PMID- 19752930
TI  - Noise and frequency chirping in external-cavity semiconductor lasers.
AB  - The noise spectra and frequency chirping of semiconductor lasers in the presence
      of arbitrary amounts of optical feedback are analyzed. Short external cavities
      with strong optical feedback are found to reduce the noise dramatically in
      semiconductor lasers, especially in the high-frequency regime. Frequency chirping
      is shown to be closely related to the nonlinear gain effect.

PMID- 19752931
TI  - Gain switching of a Nd(+3)-doped fiber laser.
AB  - We report the generation of gain-switched pulses near 1.06 microm from a Nd(+3)
      doped single-mode fiber pumped at 590 nm. For a 5-cm-long fiber, pulses of 100
      nsec at a 1-MHz repetition rate were obtained. For a 1-cm-long fiber, the pulse
      shortened to 40 nsec at repetition rates of up to 2.5 MHz for a single,
      independently drivable relaxation oscillation.

PMID- 19752932
TI  - Laser-diode side-pumped Nd:YAlO(3) laser at 1.08 and 1.34 microm.
AB  - We report efficient pulsed operation of a b-axis Nd:YAIO(3) laser rod at 1.08 and
      1.34 microm side-pumped by laser-diode arrays. Optical slope efficiencies of 27%
      and 20% were obtained at these wavelengths. Polarized absorption spectra were
      taken for Nd:YAlO(3) along the three principal axes in the region of the pump
      bands from 780 to 830 nm.

PMID- 19752933
TI  - Semiconductor-laser-pumped, mode-locked, and frequency-doubled Nd:YAG laser.
AB  - We report the demonstration of a 250-MHz mode-locked, intracavity frequency
      doubled, diode-pumped Nd:YAG laser. The laser produces 520-psec pulses at an
      average power of 76 mW and a wavelength of 532 nm. The laser has an electrical-to
      optical efficiency of 1.43% and was operated both cw and mode locked. Mode
      locking increased the average output power by 60% and eliminated noise due to
      modal competition.

PMID- 19752934
TI  - Mode-locked fiber laser with a fiber phase modulator.
AB  - FM mode-locked operation of a single-mode Nd(3+)-doped fiber laser has been
      achieved with an integrated fiber phase modulator. The technique permits a low
      loss cavity configuration, resulting in low threshold and high slope efficiency.
      Pulses of ~200-psec duration are observed at a repetition rate of 417 MHz with an
      average output power of 15 mW.

PMID- 19752935
TI  - Aperiodic ruling for the measurement of Gaussian laser beam diameters.
AB  - The use of an aperiodic ruling for the measurement of Gaussian laser beam
      diameters has been analyzed. We show that aperiodic rulings can provide spot-size
      measurements over a much broader range than available with Ronchi, triangular, or
      sinusoidal rulings used previously.

PMID- 19752936
TI  - Femtosecond pulse generation from a titanium-doped sapphire laser using nonlinear
      external cavity feedback.
AB  - A continuous-wave, argon-ion-pumped, titanium-doped sapphire laser has been
      constructed. Pulses of 80-psec duration obtained through active mode locking have
      been compressed to less than 800 fsec using nonlinear external cavity feedback.

PMID- 19752937
TI  - Spectrotemporal measurement of picosecond pulses propagating in nonlinear single
      mode fibers.
AB  - The combined effects of positive group-velocity dispersion, self-phase
      modulation, and stimulated Raman scattering experienced by 85-psec pulses
      propagating along a 960-m-long single-mode fiber are experimentally studied. The
      use of a spectrograph followed by a streak camera provides measurements in the
      spectrotemporal domain of the induced frequency modulation of a pump pulse. As a
      result, optical wave breaking, depletion of the leading edge with symmetrical
      spectral broadening, and complex instantaneous frequency structures are observed
      when the peak power of the input pulse is gradually increased to 435 W. The
      experimental method is also adapted for single-shot event analysis.

PMID- 19752938
TI  - UV saturable absorber for short-pulse KrF laser systems.
AB  - A derivative of the linear tricyclic compound, acridine, is shown to be useful as
      a saturable absorber for short-pulse KrF lasers. The saturation characteristics
      and absorption recovery of a methanol solution of acridine for a 20-psec KrF
      laser pulse are reported. We obtain a saturation fluence of 1.2 mJ/cm(2) and a
      ratio of the primary to the excited absorption cross section of 6.25:1.

PMID- 19752939
TI  - Self-focusing and self-trapping in new types of Kerr media with large
      nonlinearities.
AB  - Self-focusing and self-trapping of light in common liquid media such as Chinese
      tea, Chinese herbal medicine, and solutions of chlorophyll have been observed.
      These materials are found to be new types of natural Kerr media, and their
      nonlinear coefficients have been determined. Laser-heating-induced self-phase
      modulation in these materials has also been observed.

PMID- 19752940
TI  - Bistable ring resonator utilizing saturable photorefractive gain and loss.
AB  - We demonstrate the bistable behavior of a unidirectional ring resonator that
      employs photorefractive loss as well as photorefractive gain. The gain and loss
      are established by two-beam coupling in two separate photorefractive BaTiO(3)
      crystals. Two-beam coupling loss plays the role of a programmable saturable
      absorber. Irreversible bistability occurs when the maximum net gain exceeds
      unity, while reversable bistability is obtained when the maximum net gain is less
      than one.

PMID- 19752941
TI  - Phase measurement in frequency-doubling fibers.
AB  - Fibers were prepared for second-harmonic generation by injecting a frequency
      doubled (seed) signal with the fundamental light from a Nd:YAG laser. The
      relative phase shift between the seed and the second-harmonic light generated by
      the fiber was measured to be close to 90 degrees ( approximately 99 +/- 9.2
      degrees ). A water cell was used to sweep the relative phase of the waves with
      interferometric precision. Some physical consequences of a pi/2 phase shift are
      pointed out.

PMID- 19752942
TI  - Propagation properties of dark solitons.
AB  - We numerically study the initial-value problem of the nonlinear Schrodinger
      equation in the normal-dispersion regime of an optical fiber. A nonchirped
      hyperbolic tangent input pulse having arbitrary amplitude is found to evolve into
      a primary dark soliton having a constant amplitude and speed. The effect of the
      input amplitude is to alter the pulse width of the primary dark soliton. In
      addition, a set of secondary dark solitons of smaller amplitude moving away from
      the primary pulse is also generated. It is also shown that nonlinear dark pulses
      in optical fibers are more stable than bright pulses with respect to loss and
      noise.

PMID- 19752943
TI  - Characterization of silica-based waveguides with an interferometric optical time
      domain reflectometry system using a 1.3-microm-wavelength superluminescent diode.
AB  - Backscattering of silica-based glass waveguides is characterized for the first
      time to our knowledge by using an interferometric optical time-domain
      reflectometry system. High spatial resolution, as short as 15 microm, is obtained
      by using a newly developed 1.3-microm-wavelength superluminescent diode.
      Scattering centers produced by waveguide irregularities are clearly observed in
      glass optical waveguides. Waveguide loss and bend loss in the curved regions are
      estimated from the backscattered light intensity distribution.

PMID- 19752944
TI  - Optoelectronic multiple-valued logic implementation.
AB  - A design for optoelectronic multiple-value logic circuits that uses bistable
      laser diodes or light-emitting diodes is reported. In this multiple-valued logic
      design, an optoelectronic tristable switching circuit, or light-current mirror,
      in which two bistable light-emitting diodes are connected in parallel serves as
      the basic logic element. Five ternary logic implementations: Complement. Max(x,
      y), Min(x, y), Cycle, and Literals, have been demonstrated experimentally.
      Furthermore, any ternary logic function can be generated with the light-current
      mirror and the logic primitives.

PMID- 19752945
TI  - Experimental learning in an optical perceptronlike neural network.
AB  - An optical perceptronlike neural network employing a delta learning rule and
      consisting of input units and a single output unit is constructed.
      Photorefractive crystals are used as holographic media for the interconnections
      between the input and the output layers. The learning rate for interconnection
      weight changes is optimally determined by setting the exposure time of the
      hologram. A learning experiment verifies the learning schedule's prediction that
      a fast, stable convergence of the learning process without oscillatory action can
      be obtained.

PMID- 19752946
TI  - Polarization-sensitive surface plasmon Schottky detectors.
AB  - A polarization detector based on the excitation of surface plasmon polaritons on
      the periodically corrugated metal surface of Schottky structures is presented.
      The surface modes are only excited by light having the appropriate polarization;
      they are leaky at the metal-semiconductor interface and are thus radiated into
      the semiconductor, where they generate charge carriers. By this mechanism the
      photocurrent of the device is enhanced and depends strongly on the polarization
      angle of the incident light. By use of two detectors with different grating
      orientations the polarization of the light can be determined unambiguously.

PMID- 19752947
TI  - Experimental demonstration of internal wavelength conversion in the magnesium
      atomic filter.
AB  - We describe what is to our knowledge the first experimental demonstration of
      internal wavelength conversion in the metastable Mg atomic filter. The filter
      operates at a Fraunhofer line, thereby offering intrinsic solar background
      rejection. Incoming green Fraunhofer photons (518 nm) are absorbed by metastable
      Mg atoms in an oven cell and are converted into UV (384-nm) photons. We observed
      a green-to-UV conversion efficiency of greater than 50%.

PMID- 19752948
TI  - Alkali D-line absorption in the luminescence spectrum of solid-fluid interfaces
      under high-intensity laser excitation.
AB  - Photoluminescence spectra from the high-T(c) superconductor YBa(2)Cu(3)O(7-x),
      the semiconductor GaAs, and GaP under intense picosecond laser excitation were
      studied with their surfaces exposed to different alkali solutions. Strong
      absorption of D lines of neutral-alkali atoms was observed in these spectra.
      These absorption lines indicate that free ground-state alkali atoms were formed
      by recombination of the sublimated alkali ions with photoelectrons through
      various processes.

PMID- 19752949
TI  - Generation of tunable infrared picosecond pulses at 100 MHz by difference
      frequency mixing in KTiOPO(4).
AB  - Picosecond pulses, tunable in the wavelength range of 1.2-4.5 microm, are
      generated at a 100-MHz repetition rate in KTiOPO(4) by difference-frequency
      mixing the output of a synchronously mode-locked dye laser and a Nd:YLF laser
      that pumps the dye laser. The typical average infrared output power is in the
      milliwatt range, which represents an improvement of several orders of magnitude
      over previously reported results using other nonlinear materials in a similar
      setup with Nd:YAG as the driving source. The high average power of this infrared
      source and its broad tunability make it an attractive alternative for mode-locked
      color-center lasers.

PMID- 19752950
TI  - 432-nm source based on efficient second-harmonic generation of GaAlAs diode-laser
      radiation in a self-locking external resonant cavity.
AB  - Using a potassium niobate crystal in a modified self-locking power-buildup
      cavity, we have frequency doubled the 865-nm output from a GaAlAs laser diode.
      With 12.4 mW of input power we have obtained a unidirectional output of 0.215 mW
      at 432 nm. In contrast to previous diode doubling experiments, the output was
      both single frequency and circular Gaussian. With better optics, substantially
      higher conversion efficiencies should be possible using this technique.

PMID- 19752951
TI  - Dispersion-related multimode instabilities and self-sustained oscillations in
      nonlinear counterpropagating waves.
AB  - We show that two linearly polarized counterpropagating waves in a Kerr nonlinear
      medium with linear dispersion can exhibit multimode temporal instability. We find
      the boundary of the unstable regime and demonstrate that the fully developed
      instability results in self-sustained oscillations and the onset of chaos.

PMID- 19752952
TI  - Doppleron-induced stimulated reflection.
AB  - In a gaseous system, energy can be transferred from an intense incoming beam to a
      counterpropagating probe beam at the same frequency. The effect may be
      interpreted in terms of Doppleron processes and arises because the medium
      undergoes interaction with beams of different effective frequencies owing to the
      Doppler effect.

PMID- 19752953
TI  - Photorefractive energy exchange requiring optical activity and an electric field.
AB  - Optical-activity-supported energy transfer is explained, and a transfer of 4% is
      observed in bismuth silicon oxide with same-frequency equal-intensity beams
      having the same circular polarization. The direction of energy exchange can be
      controlled by the sign of the electric field or the sense of the circularity. In
      general, energy exchange occurs by destructive and constructive interference
      between diffracted and transmitted beams; here, with the induced grating vector
      along the [110] direction, interference cannot occur unless optical activity and
      an external electric field are present.

PMID- 19752954
TI  - Competition between subharmonic and resonating beams for photorefractive gain in
      bismuth silicon oxide.
AB  - Two beams incident upon a bismuth silicon oxide crystal are shown to give rise to
      a subharmonic halfway between the incident beams and to an oscillating beam in a
      ring resonator. It is further shown that the two beams arising are in competition
      with each other: the subharmonic power rises when the oscillating beam declines
      owing to damping of the resonator.

PMID- 19752955
TI  - Lateral and focal shifts of phase-conjugated beams in photorefractive materials.
AB  - It is predicted that when a dc electric field is present or when a probe beam
      contains temporal frequencies different from that of the pump waves a beam
      reflected from a photorefractive phase-conjugate mirror will experience lateral
      and focal shifts. These shifts are a consequence of angular dependence of the
      phase of the reflectivity and are similar to the Goos-Hanchen effect. The
      phenomenon becomes more pronounced near resonance.

PMID- 19752956
TI  - Second-harmonic generation using gratings optically written by mode interference
      in poled optical fibers.
AB  - Second-order nonlinear susceptibility gratings are induced in optical fibers by
      mode interference of high-intensity blue light in the presence of an external dc
      electric poling field. As a result, efficient second-harmonic generation can be
      obtained for any infrared design wavelength.

PMID- 19752957
TI  - Experimental observation of adiabatic compression and expansion of soliton pulses
      over long fiber paths.
AB  - In a recirculating 42-km fiber loop with round-trip loss compensated by Raman
      gain, we have used excess gain to study the influence of adiabatic energy changes
      on the propagation of soliton pulses over fiber paths of hundreds to thousands of
      kilometers. Both the measured pulse shapes and the corresponding optical spectra
      vary in agreement with simple scaling laws and maintain the expected time
      bandwidth product.

PMID- 19752958
TI  - Experimental demonstration of optical soliton switching in an all-fiber nonlinear
      Sagnac interferometer.
AB  - We demonstrate, for the first time to our knowledge, the switching of optical
      solitons. We observe switching of 93% of the total reflected energy in a
      partially transmitting integrated fiber loop mirror that makes up the
      interferometer. This result demonstrates the potential of solitons as the natural
      bits in ultrafast optical processing.

PMID- 19752959
TI  - SiO(2)-clad fibers with selectively volatilized soft-glass cores.
AB  - By using a thick-walled SiO(2) tube (25-mm outside diameter, 1-mm inside
      diameter), a soft-glass core containing Nd or Yb-Er has its alkali (and to a
      lesser extent its alkaline earth) components volatilized during drawing to give a
      good-quality laser fiber with Nd- or Yb-Er-doped cores.

PMID- 19752960
TI  - Evaluation of chromatic dispersion in W-type fibers.
AB  - Evaluation of chromatic dispersion in W-type fibers, based on the assumption that
      waveguide and material dispersion are additive effects, is examined. Actual and
      approximate dispersion of the LP(01) mode are calculated and compared for three W
      fibers. For two fibers the errors introduced by the approximate method are
      substantial, even larger than the total dispersion at most wavelengths in the
      range 1.1 microm < lambda < 1.6 microm. For a third fiber, however, the agreement
      between the actual and approximate results is close. It is shown that the
      accuracy of the approximate method improves if the wavelength derivatives of the
      index differences become smaller.

PMID- 19752961
TI  - Laser-induced fluorescence of O(3p(3)P), O(2), and NO near 226 nm: photolytic
      interferences and simultaneous excitation in flames.
AB  - Spectral overlaps between O atom two-photon transitions and one-photon O(2) and
      NO transitions near 226 nm have been studied. Excitation of photodissociating
      O(2) levels can cause anomalously high concentration population measurements of O
      atoms in flames. We find that excitation of O (3)P(1) will minimize the
      photochemical interference, and the data presented here are necessary to quantify
      the extent of such effects. Alternatively, these overlaps can be exploited to
      obtain simultaneous laser-induced fluorescence detection of O, O(2), and NO with
      a single laser.

PMID- 19752962
TI  - Optical quadratic processor using four-wave mixing in BaTiO(3).
AB  - A method has been demonstrated for performing quadratic operations by using four
      wave mixing in BaTiO(3) crystals. The processor performs a parallel vector-matrix
      vector multiplication. System operation and performance are discussed.

PMID- 19752963
TI  - Implementation of a binary optical full adder using a Venn diagram and optical
      phase conjugation.
AB  - Conventional optical pattern logic schemes can only process two input variables
      at a time. We propose a new optical spatial encoding scheme that is capable of
      simultaneously processing multiple input variables. Based on this new scheme an
      optical full adder was experimentally demonstrated using a picosecond optical
      phase-conjugation device.

PMID- 19752964
TI  - Remote wind profiling with a solid-state Nd:YAG coherent lidar system.
AB  - A solid-state coherent lidar system employing Nd:YAG lasers and heterodyne
      detection has been successfully developed, and range-resolved aerosol backscatter
      and wind-velocity measurements have been demonstrated.

PMID- 19752965
TI  - Stochastic noise in TEM(00) laser beam position.
AB  - The centroid of a single-transverse-mode laser beam fluctuates in position
      because of spontaneous emission of the laser medium into higher transverse cavity
      modes.

PMID- 19752966
TI  - Generation of KrF laser pulses on a picosecond time scale using electro-optic
      modulation.
AB  - A new technique has been developed for the generation and shaping of KrF laser
      pulses on a picosecond time scale using a fast electro-optic modulator.
      Subnanosecond electrical pulses with an amplitude much greater than the half-wave
      voltage are applied to the Pockels cell, which generates a train of short
      ultraviolet pulses. The first pulse in this train is then isolated and shortened
      to 30 psec by the combined effect of propagation through a saturated amplifier
      and optical breakdown in xenon.

PMID- 19752967
TI  - Efficient tunable solid-state laser near 630 nm using sulforhodamine 640-doped
      silica gel.
AB  - Lasing is observed near 630 nm in a sulforhodamine 640-doped silica gel pumped by
      frequency-doubled radiation from a Q-switched Nd:YAG laser. A conversion
      efficiency of 20% is obtained. The laser wavelength is tunable over 40 nm.

PMID- 19752968
TI  - Frequency-modulation mode locking of a diode-pumped Nd:YAG laser.
AB  - We investigate frequency-modulation mode locking of a diode-laser-pumped Nd:YAG
      laser. Pulses of 12-psec duration up to a repetition rate of 350 MHz have been
      obtained with no intracavity elements other than a lithium niobate phase
      modulator. These pulses are approximately twice transform limited and to our
      knowledge are the shortest pulses that have been produced by an actively mode
      locked Nd:YAG laser. When the laser was pumped by a 500-mW laser-diode array the
      average lasing power at 1.064 microm was 65 mW, which corresponds to a peak power
      of 15 W.

PMID- 19752969
TI  - Frequency-doubled, additive-pulse, mode-locked NaCl:OH(-)laser.
AB  - The output of a tunable, additive-pulse, mode-locked NaCl:OH(-) color-center
      laser has been frequency doubled using a LiIO(3) crystal. With 100-fsec pulses
      generated at 1.6 microm, stable pulses as short as 76 fsec have been obtained
      with more than 5 mW of average output power at 0.8 microm. The frequency-doubled
      pulses are tunable from 755 to 825 nm.

PMID- 19752970
TI  - Spatial ringing and central dark zone formation in absorptive nonlinear beam
      propagation.
AB  - We have observed the theoretically predicted central dark zone formation in a
      continuous-wave propagation experiment that is not due to thermal changes in the
      index of refraction. The effect has been observed in a pink ruby rod with argon
      ion and dye lasers. The results confirm the requirements of an optically thick
      and highly saturated medium for experimental observation of the effect.

PMID- 19752971
TI  - Chirped-pulse amplification of 100-fsec pulses.
AB  - Chirped-pulse amplification is used to generate 2-mJ pulses of 106-fsec duration
      in an alexandrite amplifier. Compression of the optical pulse is achieved by
      using a sequence of intracavity prisms in conjunction with diffraction gratings.
      This allows for the compensation of both linear and quadratic contributions to
      the dispersion from the amplifier.

PMID- 19752972
TI  - Search for the effect of weak photon localization in second-harmonic waves
      generated in a disordered anisotropic nonlinear medium.
AB  - The possibility of observing the effect of weak photon localization in the second
      harmonic waves generated in KH(2)PO(4) (KDP) powder is investigated and
      discussed. The two primary factors for the negative observation are that the
      second-harmonic waves are generated by different primary wave vectors because of
      multiple scattering of the primary wave in the disordered medium and that the
      scattering amplitude for the two counterpropagating second-harmonic waves are
      different because of the anisotropy of the KDP microcrystals.

PMID- 19752973
TI  - Initial demonstration of a novel broadband optical amplifier using the Kerr
      effect in an optical fiber.
AB  - A potentially ultrafast optical amplifier is outlined and demonstrated. The
      amplification involves an optical signal's modulating the polarization of a high
      power optical pump by use of the high-speed optical Kerr effect in an optical
      fiber. The pump and signal wavelengths are different, and information transfers
      to the pump wavelength. The maximum available gain is limited by the onset of
      other nonlinear effects.

PMID- 19752974
TI  - Dynamics of coupled dark and bright optical solitons.
AB  - We theoretically examine the interaction between two solitons in a double-mode
      optical fiber. The bound state between two solitons of different modes is
      investigated, including both dark and bright solitons. It is shown that
      interaction between dark solitons as well as between bright solitons is always
      attractive, but the interaction between bright and dark solitons may be
      repulsive. Analytical results are in agreement with numerical ones.

PMID- 19752975
TI  - Periodic amplification of dark solitons using stimulated Raman scattering.
AB  - The possibility of periodically amplifying dark solitons in a normally dispersive
      optical fiber is studied. It is found that, as with bright solitons, an all
      optical, repeaterless, and stable system for dark-soliton transmission at a rate
      of 20 GHz over thousands of kilometers in a lossy fiber is achievable, if
      periodic amplification using stimulated Raman scattering is incorporated.

PMID- 19752976
TI  - Soliton switching in a fiber nonlinear loop mirror.
AB  - We observe all-optical, ultrafast switching at an energy of 55 pJ in a fiber
      nonlinear-optical loop mirror. The entire 310-fsec soliton waveform switches with
      90% peak transmission. The soliton self-frequency shift lowers the peak
      transmission and splits the output pulse at higher powers, in agreement with
      numerical simulations.

PMID- 19752977
TI  - Analysis of a fused biconical single-mode star coupler.
AB  - A new type of star coupler for single-mode optical fibers is proposed. The
      geometrical configuration of the coupler is intended to be a tapered cylindrical
      ring structure. A numerical analysis yields the evolution of the light
      distribution along the coupling region and the spectral characteristics of the
      coupler. For a star coupler with 8 x 8 ports and a length of 14 mm a spectral
      width of 90 nm was calculated, if an additional loss of 0.5 dB is tolerated.

PMID- 19752978
TI  - Propagation characteristics of dual-mode elliptical-core optical fibers.
AB  - Propagation characteristics of dual-mode elliptical-core fibers are obtained by
      using a perturbation approach. It is found that for very high values of core
      aspect ratios (a/b > 2.3), the maximum possible value of the V parameter in such
      fibers is decided by the cutoff of the LP(21)(even) mode instead of the
      LP(11)(odd) mode. Further, as the core ellipticity increases, unlike the
      polarization birefringence, the birefringence between the LP(01) and the
      LP(21)(even) modes decreases and the V value, at which the LP(01) and
      LP(21)(even) modes have the same group velocities, moves toward the LP(21)(even)
      mode cutoff.

PMID- 19752979
TI  - Raman-assisted parametric frequency and polarization conversion in a birefringent
      fiber.
AB  - Highly efficient energy conversion of the pump into the downshifted parametric
      Stokes radiation resulting from the phase-matched parametric four-photon mixing
      and subsequent perpendicular Raman amplification in a birefringent fiber is
      presented. We also observed significant polarization conversion from the fast y
      axis to the slow x axis of the birefringent fiber as a consequence of group
      velocity-matched perpendicular Raman amplification of the x-polarized parametric
      Stokes radiation by the y-polarized pump.

PMID- 19752980
TI  - Formation of Bragg gratings in optical fibers by a transverse holographic method.
AB  - Bragg gratings have been produced in germanosilicate optical fibers by exposing
      the core, through the side of the cladding, to a coherent UV two-beam
      interference pattern with a wavelength selected to lie in the oxygen-vacancy
      defect band of germania, near 244 nm. Fractional index perturbations of
      approximately 3 x 10(-5) have been written in a 4.4-mm length of the core with a
      5-min exposure. The Bragg filters formed by this new technique had reflectivities
      of 50-55% and spectral widths, at half-maximum, of 42 GHz.

PMID- 19752981
TI  - Mode conversion in optically active and isotropic waveguides.
AB  - Mode conversion in optically active slab waveguides is studied both theoretically
      and experimentally. The waveguide is fabricated by homogeneously embedding
      isotropic and randomly oriented optical active material into a passive polymeric
      waveguide. The polarization rotation is measured for several configurations of a
      slab waveguide.

PMID- 19752982
TI  - Measurement of polarization-mode dispersion in single-mode fibers with random
      mode coupling: errata.

PMID- 19752983
TI  - Increased frequency conversion of Nd:YAG laser radiation with a variable
      reflectivity mirror: erratum.

PMID- 19752985
TI  - Programmable quadratic associative memory using holographic lenslet arrays.
AB  - Programmable higher-order optical interconnections between two-dimensional arrays
      of neurons are achieved by using holographic lenslet arrays and spatial light
      modulators. Basic experimental results for two-dimensional quadratic associative
      memory are reported to demonstrate its feasibility.

PMID- 19752984
TI  - Real-time tracking of a moving object in a television image using an optical
      system consisting of a liquid-crystal television and a position-sensitive device.
AB  - We describe a new optical system consisting of an active-matrix liquid-crystal
      television (AMLCTV) and a position-sensitive device (PSD) that tracks a moving
      object in television image in real time. The AMLCTV transforms the television
      signal into a two-dimensional optical image, and the PSD detects the center of
      the image projected onto the target without scanning. The advantage of this
      system is its ability to track accurately an object moving at a high speed.

PMID- 19752986
TI  - Optical memory based on heterodyne-detected accumulated photon echoes.
AB  - Optical memory based on heterodyne-detected accumulated photon echoes has been
      demonstrated in dye-doped polymers. Compared with previously developed time
      domain optical memory, writing and reading of higher bit data is possible owing
      to the superior time resolution of this method.

PMID- 19752987
TI  - GaAs/AlGaAs optical synaptic interconnection device for neural networks.
AB  - A GaAs/AlGaAs optical synaptic interconnection device for neural networks is
      reported for the first time to our knowledge. This device consists of a light
      emitting-diode array, an interconnection matrix, and a photodiode array, which
      are integrated into a hybrid-layered structure on a GaAs substrate. The device
      structure and characteristics are reported in detail. The fabricated device can
      simulate a 32-neuron system. Experimental results of the Hopfield associative
      memory with three stored vectors are also described.

PMID- 19752988
TI  - Numerical optical computing in the residue number system with outer-product
      lookup tables.
AB  - An optical outer-product architecture is presented that performs residue
      arithmetic operations with position-coded lookup tables. The architecture can
      implement arbitrary integer-valued functions of two independent variables in a
      single gate delay. The outer-product configuration possesses spatial complexity
      (a gate count) that grows linearly with the size of the modulus, and therefore
      with the system's dynamic range, in contrast to traditional residue lookup
      tables, which have quadratic growth in spatial complexity. The use of linear
      arrays of sources and modulators leads to power requirements that also grow
      linearly with the size of the modulus.

PMID- 19752989
TI  - Injectant mole-fraction imaging in compressible mixing flows using planar laser
      induced iodine fluorescence.
AB  - A technique is described for imaging the injectant mole-fraction distribution in
      nonreacting compressible mixing flow fields. Planar fluorescence from iodine,
      seeded into air, is induced by a broadband argon-ion laser and collected using an
      intensified charge-injection-device array camera. The technique eliminates the
      thermodynamic dependence of the iodine fluorescence in the compressible flow
      field by taking the ratio of two images collected with identical thermodynamic
      flow conditions but different iodine seeding conditions. The resulting images
      are, to our knowledge, the first quantitative planar measurements of mole
      fraction distributions in a nonreacting compressible flow field and allow mixing
      to be studied directly.

PMID- 19752990
TI  - Possible mechanism for laser-induced two-dimensional periodic structures by
      analogy with the Benard effect.
AB  - An explanation is presented for the formation of periodic structures on solid
      surfaces under powerful laser irradiation through an analogy to the Benard
      effect.

PMID- 19752991
TI  - Stimulated-emission cross sections of the (5)F(1)-(5)I(5) and (5)F(1)-(5)I(6)
      transitions of Pm(3+) in a phosphate glass.
AB  - We report a laser cavity measurement of stimulated-emission cross sections for
      both the (5)F(1)-(5)I(5) (0.93-microm) and (5)F(1)-(5)I(6) (1.1-microm) laser
      transitions of Pm(3+) ions in a lead-indium-phosphate glass host. The measured
      cross sections for these two transitions are 1.8 x 10(-20) (+/-11%) and 2.8 x 10(
      20) cm(2) (+/-22%), respectively. These values agree with previously reported
      values based on a Judd-Ofelt-type analysis of spectroscopic data.

PMID- 19752992
TI  - Two-dimensional waveguide modeling of leaky-mode arrays.
AB  - We examine the structure and modal gains of the leaky modes of an infinite
      periodic index-guided array by direct solution of the two-dimensional Helmholtz
      equation. These findings serve to validate the physical insights suggested by our
      previous calculations based on the effective-index method and, in particular,
      confirm the concept of guidewidth tailoring for affecting fundamental-mode
      operation of these devices at high power levels. Our newer model also provides
      new insights into the mode-selection mechanism and demonstrates clearly the
      necessity of a full twodimensional treatment if one is to describe the mode
      profiles or their relative gains accurately.

PMID- 19752993
TI  - Femtosecond-resolution pulse-front distortion measurement by time-of-flight
      interferometry.
AB  - The pulse-front distortion occurring in lenses and lens systems has been measured
      by a Michelson interferometer. In this technique the plane pulse front from one
      arm of the interferometer is used as a temporal reference level to map contour
      lines of equal propagation time on the pulse-front surface. The experimental
      arrangement is capable of detecting pulse-front distortion with a resolution of
      20 fsec, and this can be improved to approximately 1 fsec. The measured value of
      pulse-front distortion in a telescope (1.1 psec) is in good agreement with the
      calculated data.

PMID- 19752994
TI  - Subpicosecond soliton amplification and transmission using Er(3+)-doped fibers
      pumped by InGaAsP laser diodes.
AB  - Subpicosecond optical solitons in dispersion-shifted optical fibers have been
      successfully amplified with an Er(3+)-doped single-mode fiber amplifier. The
      Er(3+)-doped fiber amplifier was pumped by two InGaAsP Fabry-Perottype high-power
      laser diodes, and gains of 2.8 dB at 1.535 microm and 3.8 dB at 1.552microm were
      obtained for solitons with pulse widths of 0.7-0.9 psec and peak intensities as
      high as 40 W. The transmission characteristics of the amplified solitons through
      a long dispersion-shifted fiber are also reported.

PMID- 19752995
TI  - Temporal and spectral self-shifts of dark optical solitons.
AB  - We report the discovery of temporal and spectral self-shifts of dark optical
      solitons propagating in single-mode fibers. These shifts become increasingly
      pronounced as the intensity and the fiber length are increased. We show that our
      data are in quantitative agreement with numerical solutions to a modified
      nonlinear Schrodinger equation that includes the Raman contribution to the
      nonlinear refractive index.

PMID- 19752996
TI  - Self-localized light: launching of low-velocity solitons in corrugated nonlinear
      waveguides.
AB  - We show that stationary gap solitons are just a limiting case of a wider set of
      (slowly) moving solitons associated with the photonic stop gap of a periodic
      nonlinear structure. We give an analytic description of these solitons and
      provide the prescription for launching such solitons in a realistic waveguide
      geometry.

PMID- 19752997
TI  - Correction of thermal blooming by optical phase conjugation.
AB  - We have observed accurate correction of laser-induced thermal blooming by optical
      phase conjugation. The thermal blooming produced up to a 36-fold increase in the
      far-field spot diameter and up to a 60-fold decrease in the far-field peak
      intensity. Stimulated Brillouin scattering was used as the phase-conjugate mirror
      with a reflectivity of 35% to 65%. A previously published theory regarding phase
      conjugate correction of intensity-dependent aberrations suggested that nonunity
      reflectivity would adversely affect the phase conjugate's ability to compensate
      for thermal blooming. We found no evidence of this being the case.

PMID- 19752998
TI  - All-optical intermodal switch using periodic coupling in a two-mode waveguide.
AB  - An intermodal switch based on optically induced (through the Kerr effect)
      periodic coupling in a two-mode waveguide is described and demonstrated. A high
      power pump beam injected into the two modes of the waveguide produces a periodic
      modulation of the refractive-index profile with a period equal to the modal beat
      length, which causes coupling between the two modes of a simultaneously injected
      probe beam. The operating principle was successfully demonstrated in an
      elliptical-core two-mode fiber with counterpropagating pump and probe beams.

PMID- 19752999
TI  - Transient gain and cross talk in erbium-doped fiber amplifiers.
AB  - Transient gain saturation and recovery with 110-340-microsec time constants were
      observed in erbium-doped fiber amplifiers. This slow response reduces the effects
      of saturation-induced cross talk and intermodulation distortion associated with
      multichannel signal amplification. In a two-channel amplification experiment,
      negligible saturation-induced cross talk was measured at signal modulation
      frequencies >5 kHz. Increased suppression of saturation-induced cross talk was
      achieved through feed-forward compensation to reduce low-frequency gain
      fluctuations.

PMID- 19753000
TI  - Anisotropic couplers composed of nonidentical cores with nonaligned optical axes.
AB  - The vector modal patterns of anisotropic fiber couplers composed of nonidentical
      cores with nonaligned optical axes are presented. The four normal modes have
      different propagation constants with the corresponding electrical-field vectors
      pointing in different directions.

PMID- 19753001
TI  - Sensitivity-enhanced, common-mode-compensated Mach-Zehnder fiber-optic sensor
      circuit with electro-optic feedback.
AB  - A Mach-Zehnder fiber-optic sensor circuit incorporating an optical compensation
      circuit to reduce errors from common-mode perturbations and electro-optic
      feedback to enhance measurand sensitivity is proposed and demonstrated.
      Experimental results show that the phase bias and the feedback constant can be
      adjusted to yield an operating region with negligible sensitivity to common-mode
      perturbations and a measurand sensitivity an order of magnitude above that
      expected from an equivalent conventional Mach-Zehnder sensor, in good agreement
      with theory.

PMID- 19753002
TI  - High-packing-density multichannel integrated-optic modules in LiNbO(3) for a
      programmable correlation of binary sequences.
AB  - Two 10-channel integrated-optic device modules have been constructed and tested.
      The architecture common to both modules consists of a LiNbO(3) composite
      waveguide 1.0 cm x 2.0 cm in size in which a channel-waveguide array, a planar
      waveguide, a linear microlens array, an electro-optic Bragg modulator array or an
      acousto-optic and electro-optic Bragg modulator array, and a large-aperture lens
      are integrated. A novel scheme that employs a linear ionmilled planar microlens
      array was devised to excite the entire channel-waveguide array simultaneously,
      and thus greatly facilitate testing and application of the two device modules.
      The performance characteristics obtained in programmable correlation of binary
      sequences are also presented.

PMID- 19753003
TI  - Integration of holographic optical elements with polymer gelatin waveguides on
      GaAs, LiNbO(3), glass, and aluminum.
AB  - We have observed waveguiding in thin films of polymer gelatin on GaAs, LiNbO(3),
      glass, and aluminum substrates. A graded-index profile can be induced in the
      gelatin layer and tuned by wet processing. This makes it possible to form
      waveguides on any smooth surface. Locally sensitizing the gelatin waveguide with
      ammonium dichromate allows us to integrate single and multiplexed gratings on the
      same substrate to perform various functions for optical interconnects and signal
      processing. A waveguide grating coupler that converts free-space TEM(00) laser
      light to a two-dimensional spherical guided wave with 50 degrees angle of
      divergence has also been demonstrated. An optical clock distribution network on
      wafer-scale integrated circuits is feasible with this new technology.

PMID- 19753004
TI  - Programmable fiber/integrated-optics bipolar tap.
AB  - A programmable bipolar tap implementation is described. The proposed scheme
      utilizes fiber and integrated-optics technology in conjunction with twos
      complement number representation and digital multiplication by an analog
      convolution algorithm. Simple experimental verification of the scheme is
      presented.

PMID- 19753005
TI  - Nonlinear prism coupling with nonlocality.
AB  - The characteristics of prism coupling of finite-width beams into nonlinear
      waveguides composed of media with diffusive nonlinearities (thermal, etc.) are
      calculated by including a one-dimensional diffusion equation for the nonlocal
      nonlinearity. The resulting longitudinal feedback leads to bistability, and the
      threshold value for the minimum diffusion length varies inversely with the
      angular detuning.

PMID- 19753006
TI  - All-optical error-signal generation for backpropagation learning in optical
      multilayer neural networks: erratum.

PMID- 19753007
TI  - Derivation of a unified transfer function in the theory of flicker.
AB  - In the study of the human vision system based on the temporal-modulation transfer
      function curve, Kelly [J. Opt. Soc. Am. 59, 1665 (1969); 61, 537 (1971)] proposed
      two different diffusion models. In Kelly's second model the theoretical results
      fitted well with his experimental data in a wide range of adaptation levels.
      However, from a mathematical point of view, this model was based on formal
      assumptions without reasonable justifications. The purpose here is to derive a
      new transfer function utilizing a more rigorous mathematical development and to
      show that it is compatible with Kelly's two models.

PMID- 19753008
TI  - Phase-front measurements of an injection-locked AlGaAs laser-diode array.
AB  - The phase-front quality of the primary spatial lobe emitted from an injection
      locked gain-guided AlGaAs laser diode array is measured by using an equal-path,
      phase-shifting Mach-Zehnder interferometer. Root-mean-square phase errors of
      0.037 +/- 0.003 wave (lambda/27) are measured for the single spatial lobe, which
      contained 240-mW cw output power in a single longitudinal mode. This phase-front
      quality corresponds to a Strehl ratio of S = 0.947, which results in a 0.23-dB
      power loss from the single lobe's ideal diffraction-limited power. These values
      are comparable with those measured for single-stripe index-guided AlGaAs lasers.

PMID- 19753009
TI  - Optical heterodyne sensor using the Goos-Hanchen shift.
AB  - A new sensing scheme, capable of measuring various quantities using the Goos
      Haanchen shift in the polarization phase domain, is proposed. The phase
      retardation between s and p polarizations on total reflection is enhanced by
      using multiple reflections in a plane-parallel transparent plate. This phase
      shift can be sensitively and stably detected using an in-line heterodyne method.
      As an application of this method, a displacement sensor utilizing the deflection
      of a light beam by a lens is developed. This displacement sensor has a resolution
      of 60 nm over a dynamic range of 120 microm. Good agreement between theoretical
      and experimental results is shown.

PMID- 19753010
TI  - Compressible boundary-layer density cross sections by UV Rayleigh scattering.
AB  - Rayleigh scattering has been used to image density cross sections of a
      compressible boundary layer for the first time to our knowledge. These cross
      sections were made from a Mach 2.5 boundary layer by illuminating it with a UV
      laser sheet from an argon-fluoride laser (193 nm). Since Rayleigh scattering is
      linearly proportional to density, quantitative values are measured, which leads
      to new instantaneous and statistical information about the structure of this
      turbulent field.

PMID- 19753011
TI  - Direct formation of planar holograms and noise gratings at 820 nm in bleached
      silver-halide emulsions.
AB  - Experimental results are presented on the efficiency of holographic transmission
      gratings formed in bleached silver halide emulsions (Agfa-Gevaert 8E75HD) with
      illumination at 820 nm. For comparison, data for planar gratings recorded at 780
      and 632.8 nm in emulsions that were similarly processed are also given.
      Measurement of the spectral optical density indicates that the useful holographic
      recording range extends to 840 nm. We conclude with a comparison of the
      efficiency of noise gratings formed in this emulsion at 632.8, 780, and 820 nm
      and a discussion of the implications of these results.

PMID- 19753012
TI  - Nonconventional joint-transform correlator.
AB  - A nonconventional joint-transform correlator (NJTC) is discussed. We show that
      the shift-invariant property of the usual joint-transform arrangement can be
      preserved. The advantages of the NJTC are the efficient use of the light source,
      the use of smaller transform lenses, higher correlation peaks, and a higher
      carrier fringe frequency.

PMID- 19753013
TI  - Pattern recognition with a bidirectionally coupled nonlinear-optical-element
      system.
AB  - A parallel pattern-recognition system composed of coupled-element tristable
      optical components is proposed. Each elemental component is an optical ring
      resonator in which three cells of nonlinear refractive-index material are placed
      between mirrors. The basic idea is derived from the symmetry-breaking instability
      caused by the unbalance between counterpropagating input light fields that excite
      the nonlinear refractive-index material (the cell) bidirectionally. Input spatial
      patterns composed of the arbitrary combinations of [0, 0, 0], [1, 1, 0], [0, 1,
      1], and [1, 0, 1] are found to be recognized at once, yielding the capacity of
      2/3 bit/cell.

PMID- 19753014
TI  - Influence of interconnection weight discretization and noise in an optoelectronic
      neural network.
AB  - The effect of discretizing interconnection weight strengths in an optoelectronic
      learning neural network based on the backpropagation algorithm is investigated.
      We discuss how discretization arises in such an implementation. Using computer
      simulations we find that learning performance, as tested on the two-input XOR
      problem, is poor but that the addition of noise to the system results in
      substantial improvement.

PMID- 19753015
TI  - Annular-slot arrays as far-infrared bandpass filters.
AB  - Arrays of both annular and square annular slots in a conducting sheet on a
      dielectric substrate have been fabricated photolithographically. The structures
      are shown to behave as bandpass filters in the far infrared, with a resonant
      wavelength slightly larger than the average circumference or perimeter of the
      slot. The measured far-infrared transmittance of the annular array is
      approximately 76% of that predicted by theory, while its resonant frequency
      agrees with theory to within 5%.

PMID- 19753016
TI  - Saturated absorption in SF(6) with double-velocity selection.
AB  - Doppler-free saturated absorption of a weak CO(2) laser probe on SF(6), which is
      caused by two noncollinear pump beams, is reported. A small-linewidth angular
      dependence was observed and can be predicted in agreement with a fifth-order
      perturbation calculation for a two-level atom.

PMID- 19753017
TI  - Analysis of grating-coupled surface-emitting lasers.
AB  - Grating-coupled surface-emitting diodes are modeled and analyzed in terms of
      radiation power, threshold gain, and saturation effects. We find that the
      dominant (i.e., the lowest-loss) mode radiates poorly, while a weaker mode has a
      much higher radiation power and appears dominant if only the radiated power is
      measured. The weakly radiating mode effectively lowers the device efficiency and
      broadens the far-field radiation pattern. We also show that an increase in the
      length of the distributed Bragg reflector sections at the end can double the
      radiated power and reduce the threshold gain.

PMID- 19753018
TI  - Generation of 36-fsec pulses near 775 nm from a colliding-pulse passively mode
      locked dye laser.
AB  - We report the passive mode locking of a cw Rhodamine 700 dye laser using the
      saturable absorber DDI. Pulses as short as 36 fsec near 775 nm have been produced
      in a colliding-pulse mode-locked dye laser with adjustable intracavity group
      velocity dispersion.

PMID- 19753019
TI  - Solitary pulses in an amplified nonlinear dispersive medium.
AB  - An analytical solution is obtained for solitary pulse propagation in an amplified
      nonlinear dispersive system. For a homogeneously broadened gain medium, this
      solitary pulse has a hyperbolic secant amplitude and a hyperbolic tangent
      instantaneous frequency variation. The pulse is a gain-guided pulse in either the
      positive or the negative dispersion regime as well as in the self-focusing or
      self-defocusing regime. A dark solitary pulse that has a hyperbolic tangent
      amplitude and a similar instantaneous frequency variation is also obtained.

PMID- 19753020
TI  - Determination of the phase of the complex nonlinear refractive index by transient
      two-wave mixing in saturable absorbers.
AB  - The ratio of the imaginary part to the real part of the complex nonlinear
      refractive index has been measured by transient two-wave mixing in acridine
      orange-doped fluorophosphate glass, fluorescein-doped boric-acid glass, and ruby
      at argon-ion wavelengths. The method enables the individual signs of the
      components of the nonlinear index to be obtained. A simple theory based on a
      single homogeneously broadened absorption from the ground state agrees with
      measurements of the phase of the nonlinear index in acridine but not in
      fluorescein, where our data suggest that excited-state absorption plays an
      important role.

PMID- 19753021
TI  - Theory of thermal blooming correction by phase conjugation.
AB  - We predict accurate correction of thermal blooming by phase conjugation, for the
      case of a nonunity-magnitude reflection coefficient, over a wide range of easily
      realized experimental conditions. Diffusion relaxes a thermal grating that would
      otherwise spoil phase-conjugate correction. Phase conjugation is predicted to
      correct thermal blooming caused by continuous-wave lasers, collimated or loosely
      focused lasers, pulsed lasers blooming in gases, and broadband lasers.

PMID- 19753022
TI  - Measurement of the third-order hyperpolarizability of platinum poly-ynes.
AB  - We present the measurements of the third-order polarizability (gamma) of several
      platinum poly-ynes obtained using picosecond laser pulses. The real part of gamma
      was measured using the optical Kerr effect with a 1.064-microm pump and a 0.532
      microm probe. The imaginary part was evaluated from the two-photon absorption
      coefficient determined at 0.532 microm. The platinum poly-ynes had low absorption
      in the visible and the near-infrared wavelengths.

PMID- 19753023
TI  - High-sensitivity, single-beam n(2) measurements.
AB  - We present a simple yet highly sensitive single-beam experimental technique for
      the determination of both the sign and magnitude of n(2). The sample is moved
      along the z direction of a focused Gaussian beam while the repetitively pulsed
      laser energy is held fixed. The resultant plot of transmittance through an
      aperture in the far field yields a dispersion-shaped curve from which n(2) is
      easily calculated. A transmittance change of 1% corresponds to a phase distortion
      of approximately lambda/250. We demonstrate this method on several materials
      using both CO(2) and Nd:YAG laser pulses.

PMID- 19753024
TI  - Nearly degenerate four-wave mixing investigation of period doubling in
      semiconductor lasers.
AB  - The nearly degenerate four-wave mixing technique is used to investigate the
      physical origin of period doubling in the route toward chaos. This spectroscopic
      approach identifies resonantly enhanced nearly degenerate four-wave mixing
      processes as being responsible for the generation of subharmonic frequencies. The
      technique presented in the case of GaAlAs semiconductor lasers could be applied
      to the study of monomode instabilities occurring in any laser or bistable
      devices.

PMID- 19753025
TI  - Picosecond photorefractive response of GaAs:EL2, InP:Fe, and CdTe:V.
AB  - Measurements and theoretical calculations are presented for the photorefractive
      effect in three semi-insulating semiconductors (GaAs:EL2, InP:Fe, and CdTe:V)
      using 29-psec pulses at a wavelength of 1.06 microm. The photorefractive gain is
      largest in the CdTe crystal and smallest in our InP sample. The major differences
      between the materials responsible for this are the electro-optic coefficients,
      the mobilities, the absorption coefficients, and the amount of electron-hole
      competition.

PMID- 19753026
TI  - Polarization-dependent and intensity-dependent phase mismatch of second-harmonic
      generation in optical fibers.
AB  - The second-harmonic dependence on the input fundamental light has been measured
      in optical fibers having a chi((2)) induced by seeding. The results are explained
      with a model that includes self-phase and cross-phase modulation in the equations
      governing second-harmonic generation and seeding. This leads to an intensity
      dependent phase mismatch whose strength also depends on the relative
      polarizations of the fundamental and second-harmonic lights. During seeding, the
      same effects result in a chi((2)) grating detuned from exact phase matching.

PMID- 19753027
TI  - Fiber-optic sensor for humidity.
AB  - A novel fiber-optic humidity sensor is described. It is based on reversible
      sorption of water from the ambient atmosphere in a porous thin-film
      interferometer that sits on the tip of a fiber. The sorbed water changes the
      refractive index of the thin films and thus the reflectivity of the
      interferometer; the resulting modulation of the reflected intensity is detected.
      The sensor is insensitive to electromagnetic interference and aggressive
      chemicals and is extremely small (micrometers).

PMID- 19753029
TI  - Optical liquid-crystal-television correlator for particle-image-velocimetry
      processing.
AB  - An application of an inexpensive liquid-crystal television as a processor for
      full-field velocity measurement techniques that require two-dimensional
      correlation is presented. With the use of nonspecialized optics, the results
      compare well with digital correlations.

PMID- 19753028
TI  - Prescription for beam design: optimizing power transport to a target.
AB  - A prescription is derived for determining the beam that delivers the maximum
      power to a specified target for a given allowed aperture.

PMID- 19753030
TI  - Compact parallel real-time programmable optical morphological image processor.
AB  - Based on the parallel-processing and interconnection capabilities of optics, a
      novel, compact, real-time programmable parallel optical morphological filter is
      proposed and demonstrated. Using a real-time polarization-encoded image-casting
      scheme, some proof-of-principle experimental results are presented.

PMID- 19753031
TI  - Demonstration of an optical inhibitory neural network.
AB  - An optical inhibitory neural network with lateral interconnections between units
      is demonstrated. Separate device responses, inversely proportional and sigmoid,
      are utilized for inhibitory and excitatory units, respectively. Preliminary
      experimental results for an edge enhancement illustrate the versatility of the
      network. The inverted semilinear transfer function for a microchannel spatial
      light modulator combined with a polarizer produces the inhibitory signal
      optically without performing optical signal subtraction.

PMID- 19753032
TI  - Sensitive photon detector based on selective laser ionization.
AB  - A selective laser ionization photodetector (SLIP) is proposed and demonstrated.
      The SLIP uses an atomic-gas target as a detection element, instead of the
      photoelectric surface in photomultiplier tubes. The atomic gas resonantly absorbs
      the signal radiation to be detected and then is selectively photoionized by an
      intense laser beam. As a result, it can be expected that the SLIP will provide
      high quantum efficiency in a limited detection bandwidth. An analysis is made,
      and an initial-stage experiment on the SLIP is described.

PMID- 19753033
TI  - Picosecond gyrolaser.
AB  - The reduction of the frequency-locking problem is evaluated analytically for an
      active laser gyroscope in which active coupling of the longitudinal modes in each
      direction leads to the formation of counterpropagating short pulses. With proper
      precautions, an important reduction of the lock-in frequency is expected.
      Numerical calculations confirm this possibility. The use of inexpensive systems
      based on laser diodes for the pump or perhaps the laser medium is proposed to
      obtain sensitive devices without mechanical dither.

PMID- 19753034
TI  - Frequency fluctuations of a diode-pumped Nd:YAG ring laser.
AB  - We have measured the spectral density of the frequency fluctuations of a diode
      pumped single-mode monolithic Nd:YAG ring aser by locking a Fabry-Perot resonator
      to the laser frequency. The fluctuations approach the limit due to spontaneous
      emission (the Schawlow-Townes limit) at frequencies above 80 kHz. The inherent
      frequency stability of these lasers makes them attractive as a potential light
      source for gravitational-wave interferometers.

PMID- 19753035
TI  - Atomic wavelength reference for a temperature-tunable 1341-nm Nd(3+):YAlO(3)
      laser.
AB  - A miniature monolithic diode-pumped temperature-tunable Nd(3+):YAlO(3) laser can
      be set anywhere within its 1-nm tuning range with a long-term stability of 1 pm
      by using an optogalvanic signal from the 1341.1686-nm 5s-3p transition in helium
      and the measured temperature tuning rate of the laser.

PMID- 19753036
TI  - Laser-diode-pumped mirror-free Er(3+)-doped fiber laser.
AB  - We have demonstrated 1.47-microm laser-diode-pumped Er(3+)-doped fiber laser
      operation at 1.552 microm, in which a cleaved fiber facet with 4% reflectivity is
      used as the output mirror. The pump source is a 1.47-microm InGaAsP laser diode
      inserted into the fiber laser cavity. End pumping a 7-m-long Er(3+)-doped fiber
      yields an output power of 1 mW for an absorbed pump power of 60 mW and a slope
      efficiency of 6.25%.

PMID- 19753037
TI  - High-quantum-efficiency Er(3+) fiber lasers pumped at 980 nm.
AB  - Significant improvements in the operation of Er(3+)-doped silica fiber lasers
      operating at wavelengths between 1.5 and 1.6 microm are reported. The use of 980
      nm as the pump wavelength provides an output that is limited mainly by the
      quantum efficiency of the lasing process. It is thus considerably more efficient
      than previous results using ~810-nm pumping, where excited-state absorption
      degrades the lasing performance. Operation at three discrete output wavelengths
      is observed and is accounted for by studying gain across the lasing bandwidth.

PMID- 19753038
TI  - Generation of intense 25-fsec pulses by a pulsed laser system.
AB  - A pulsed femtosecond dye laser is demonstrated with relaxed stability
      requirements, improved output reproducibility, and significant pulse shortening.
      Starting with a sequence of approximately 350 pump pulses of a Nd:glass laser
      (repetition rate 6 Hz, duration 1.3 psec), pulses of 25 fsec and 10 nJ are
      generated at 566 nm. A non-colliding-pulse, mode locked ring laser is used with
      dispersion compensation and the dyes Rhodamine 6G, DQOCI, and DTCI. The evolution
      of the pulse parameters as a function of cavity round trips is investigated.

PMID- 19753039
TI  - Generation of a train of fundamental solitons at a high repetition rate in
      optical fibers.
AB  - By adiabatic amplification of a periodically modulated cw signal in an optical
      fiber, a train of approximately independent solitons can be generated at a high
      repetition rate (up to the terahertz range). These pulse trains can be produced
      with fibers having slowly varying dispersion as well.

PMID- 19753040
TI  - Soliton trapping in birefringent optical fibers.
AB  - We show experimentally the trapping of orthogonally polarized solitons in
      birefringent optical fibers with polarization dispersions as high as 90 psec/km.
      Solitons along two axes of a fiber compensate for the polarization dispersion by
      shifting their frequencies, and we observe frequency splitting up to 1.03 THz for
      a polarization dispersion of 80 psec/km. For a 20-m fiber the energy required to
      compensate for the polarization dispersion is ~84 pJ, and for a 76m fiber the
      energy required reduces to ~64 pJ.

PMID- 19753041
TI  - Transmission through plasma created by laser-induced breakdown of water droplets.
AB  - The temporally and spatially resolved transmission is measured with a green probe
      beam through the plasma created by an intense near-IR beam that is incident upon
      a water droplet. We report the propagation speed of the expanding plasma and the
      evolution of the transmission decrease and recovery at various locations along a
      line in the direction of the IR beam.

PMID- 19753042
TI  - Voltage-controlled photorefractive effect in paraelectric KTa(1-x)Nb(x)O(3):Cu,V.
AB  - Experimental results that demonstrate the formation of photorefractive gratings
      in KTN:Cu,V in theparaelectric phase are presented. These gratings are formed
      using the quadratic electro-optic effect, which allows amplitude modulation of
      the diffracted beam by an external electric field. High diffraction efficiencies
      of over 50% in a 3-mmthick sample and amplitude modulation of the diffracted beam
      by an external field at frequencies of up to 20 kHz were observed.

PMID- 19753043
TI  - Application of the BaTiO(3) beam-fanning optical limiter as an adaptive spatial
      filter for signal enhancement in pulsed infrared laser-excited photothermal
      spectroscopy.
AB  - A method for obtaining a high-contrast visible-light signal from infrared
      absorption in low-absorbance samples is described. This method is based on a beam
      fanning optical limiter in photorefractive BaTiO(3). The resulting signal is not
      linear but does exhibit an enhanced signal-to-background ratio that is 4 to 6
      orders of magnitude better than that of conventional infrared absorption
      spectrophotometry in the shot-noise limit. A simple model for the beam-fanning,
      optical-limiter-based, pulsed-laser-excited photothermal spectroscopy detector is
      found to describe the experimental data adequately. This technique using
      photothermal spectroscopy detection may have advantages for rapid signal analysis
      and for two-dimensional visible imaging of infrared absorption.

PMID- 19753044
TI  - Correlation of defect centers with second-harmonic generation in Ge-doped and Ge
      P-doped silica-core single-mode fibers.
AB  - The origin of frequency doubling in Ge-doped silica-core single-mode glass fibers
      has been investigated with electron-spin-resonance spectrometry. Correlations
      have been observed between the conversion efficiency and the light-induced Ge E'
      center concentration.

PMID- 19753045
TI  - Determination of a dielectric waveguide propagation constant using a
      multifilament-current model.
AB  - A moment method using a multifilament-current model is presented to analyze the
      modes propagating in a cylindrical dielectric waveguide. In this model,
      analytically derivable fields of filamentary electric and magnetic currents (of
      yet unknown propagation constant and amplitude) are used to simulate the field of
      each mode inside and outside the guiding core. A simple point-matching procedure
      is subsequently used to enforce the boundary conditions at the core periphery and
      results in a homogeneous matrix equation. The longitudinal propagation constant
      of each mode and the currents that yield the field distribution of this mode are
      then found by solving this equation. As an example, a circular dielectric
      waveguide is analyzed and the results are presented.

PMID- 19753046
TI  - Acousto-optical modulation method for measuring the beat length of a linearly
      birefringent optical fiber.
AB  - A simple, accurate, and nondestructive method based on acousto-optical modulation
      of the polarization and the optical frequency in a linearly birefringent fiber is
      proposed for measuring the beat length of the fiber. Short beat lengths can be
      measured by this method with an accuracy of the order of 1%. This method can also
      be used to identify the local polarization axes of the fiber.

PMID- 19753047
TI  - 1 x 2 wavelength-selective switch for three-channel wavelength-division
      multiplexing systems.
AB  - A 1 x 2 wavelength-selective optical switch for three-channel wavelength-division
      multiplexing systems is proposed and tested. The switch is constructed by a
      cascade connecting three switch elements, each of which controls the polarization
      state of a certain wavelength of light. A 1 x 2 switch for a three-channel
      multimode fiber system (channel wavelengths 1.2, 1.25, and 1.3 microm) is
      fabricated. Its measured insertion losses and cross-talk attenuations are <0.9
      and >14.7 dB, respectively, for all switching modes and all channels.

PMID- 19753048
TI  - General principles of scanning tunneling optical microscopy.
AB  - A homogeneous propagating wave falling onto submicrometer objects is partially
      diffracted into evanescent waves. The use of a scattering probe of subwavelength
      size can convert the evanescent waves into homogeneous ones and make their
      detection possible. The resulting propagating waves can then provide information
      about the subwavelength object. Relations with preliminary experiments are
      discussed.

PMID- 19753049
TI  - Observation of domain patterns induced by ultrasound pulses in a nematic liquid
      crystal film.
AB  - The homeotropically aligned nematic liquid-crystal layer with a free circular
      edge is studied. Domain patterns induced by high-frequency ultrasound pulses are
      observed for the first time to our knowledge. The pattern changes for different
      incident angles of the ultrasound and can be enhanced by a quasi-static electric
      field.

PMID- 19753050
TI  - Observation of amplitude squeezing from semiconductor lasers by balanced direct
      detectors with a delay line.
AB  - Simultaneous measurement of the signal-noise level and the corresponding shot
      noise level using balanced direct detectors with a delay line is demonstrated. We
      have observed 1.3-dB squeezing from a constant-current-driven semiconductor
      laser, which is consistent with 3-dB squeezed noise at the output of the laser
      when the detection efficiency is taken into account.

PMID- 19753051
TI  - Circuit theory of multielement laser diodes.
AB  - A general theory of noise and small-signal modulation of multielement laser
      diodes in the saturated regime is established. Nonlinear elements are connected
      to the ports of a linear-optical circuit oscillating in a single electromagnetic
      mode. The laser amplitude and phase fluctuations are expressed simply in terms of
      the scattering matrix of the linear-optical circuit at any baseband frequency and
      for an arbitrary electronic feedback. The case of a single laser diode and a
      single detector is treated to demonstrate this method. The correlation between
      optical power and electrical voltage fluctuations is shown to disappear at large
      output powers, in agreement with recent experiments.

PMID- 19753052
TI  - Liquid excimers: lasing Xe(2) and Kr(2) in liquid argon.
AB  - By pumping a small cryogenic cell with a 40-nsec, 1-MeV e-beam pulse, we have
      excited lasing in dilute mixtures of xenon or krypton in liquid argon. The lasing
      occurred at 175 nm for the excimer Xe(2) and at 147 nm for Kr(2).

PMID- 19753053
TI  - Low-frequency self-pulsations in asymmetric external-cavity semiconductor lasers
      due to multiple-feedback effects.
AB  - We investigate the dynamical stability of external-cavity semiconductor lasers
      with deliberate tilt asymmetries. Experimentally observed low-frequency self
      pulsations are explained by small-signal analysis based on a new rateequation
      model that uses a time-dependent effective reflectivity to include multiple
      feedback effects. We observe and explain the dependence of the self-pulsation
      frequency on the strength and degree of asymmetry of the feedback, on the
      injection current, and on the external-cavity length. These results are important
      in interpreting instabilities, chaos, and other complex dynamical phenomena in
      external-cavity semiconductor lasers.

PMID- 19753054
TI  - Scalable, end-pumped, diode-laser-pumped laser.
AB  - A novel technique for scaling end-pumped lasers is demonstrated using three diode
      laser arrays to pump a single Nd:YAG laser. Diffraction-limited output with a 58%
      slope efficiency was obtained. Simple arguments indicate that this method should
      allow at least an order of magnitude increase in pump power, compared with that
      from a single high-power diode array, to be focused into the same fixed-mode
      volume of the pumped laser. Such a scheme may be particularly useful with low
      gain, quasi-three-level, or tunable lasers.

PMID- 19753055
TI  - Glass fiber laser at 1.36 microm from SiO(2):Nd.
AB  - By adding 14 mol % P(2)O(5) to the core of a SiO(2):Nd fiber, laser emission was
      obtained at 1.36 microm. From the fluorescent spectra and laser thresholds for
      the (4)F(3/2) to (4)I(11/2) and (4)F(3/2) to (4)I(13/2) transitions, the net gain
      at 1.36 microm is 0.024 dB/mW, and the ratio of excited-state absorption (the
      (4)F(3/2) to (4)G(7/2) transition) to stimulated emission is estimated to be
      0.78.

PMID- 19753056
TI  - Theoretical modeling of erbium-doped fiber amplifiers with excited-state
      absorption.
AB  - Numerical solution of a general rate-equation model of an erbium-doped fiber
      amplifier highlights several important features of the device. A difference in
      strong-signal gain between copropagating and counterpropagating signal pump
      schemes in the presence of pump excited-state absorption is predicted, and this
      is confirmed by experimen. The detriment in the noise figure previously
      associated with counterpropagating schemes for only small-signal conditions is
      shown to be similar for strong signals, corresponding to a power-amplifier
      operating regime. In addition, a correction to the noise figure is given for the
      limit of a low-gain amplifier.

PMID- 19753057
TI  - 20-GHz soliton amplification and transmission with an Er(3+)-doped fiber.
AB  - A 20-GHz soliton burst pulse train at 1.552 microm is successfully amplified with
      a 3.5-m Er(3+)-doped fiber amplifier. It is possible to transmit 20-GHz solitons
      with an N = 1 soliton power of 10 mW and a pulse width of 10 psec. The Er(3+)
      doped fiber has a doping concentration of 1370 parts in 10(6) and is pumped by
      InGaAsP laser diodes. The gain of the fiber is determined by the average input
      power because of the slow gain recovery time.

PMID- 19753059
TI  - Forward mode coupling in periodic nonlinear-optical fibers: modal dispersion
      cancellation and resonance solitons.
AB  - In the presence of an intensity-dependent frequency chirp, periodic linear mode
      coupling between two copropagating waves may counteract their temporal walkoff
      and lead to a new type of optical soliton that propagates at any wavelength.

PMID- 19753058
TI  - Amplification of femtosecond optical pulses using a double confocal resonator.
AB  - We experimentally examine a class of multipass amplifiers based on an open double
      confocal resonator. A preamplifier provides a gain of 800. An intermediate-stage
      amplifier produces pulse energies of 2 microJ for only 1.4 W of pump power at a
      repetition rate of 10 kHz. A third structure, which includes a four-prism
      sequence, provides on each pass adjustable forms of the four basic pulse-shaping
      mechanisms of saturable gain, saturable absorption, group-velocity dispersion,
      and self-phase modulation, as well as spectral filtering. This latter structure
      also reversibly lengthens the pulse duration in the gain medium from 50 fsec to
      over 450 fsec.

PMID- 19753060
TI  - Compression of Stokes pulses generated through a parametric four-photon mixing
      process in a birefringent optical fiber.
AB  - We demonstrate the compressibility of Stokes pulses at a 1.075-microm wavelength
      that are generated through the parametric four-photon mixing process in a highly
      birefringent single-mode fiber pumped by 35-psec pulses at 1.053 microm from a cw
      mode-locked Nd:YLF laser. With a 300-m fiber and a grating pair the pump pulses
      at 1.053 microm are compressed to 350 fsec, with an average output power of 370
      mW after compression. With a different input pump polarization angle and a
      different grating separation the Stokes pulses are compressed to 470 fsec, with
      the same average output power after compression.

PMID- 19753061
TI  - Suppression of low-intensity features using second-harmonic generation and
      amplification.
AB  - A novel technique, based on second-harmonic generation and amplification, is
      proposed that may be applied to the suppression of prepulses in amplifier
      configurations. Simultaneously, peak-to-satellite contrast ratios may be
      enhanced, pulse energies may be increased, and pulse durations may be reduced in
      an amplification scheme that eliminates amplified spontaneous emission.

PMID- 19753063
TI  - Efficient phase conjugation of a cw low-power laser diode in a short Cs vapor
      cell at 852 nm.
AB  - Up to 50% cw phase-conjugate reflectivity has been obtained with a 30-mW diode
      laser at 0.85 microm by means of resonant degenerate four-wave mixing on an
      optically thick, 1-mm-long Cs vapor cell. Self-oscillation of a Fabry-Perot
      cavity containing this Cs cell is demonstrated.

PMID- 19753062
TI  - Highly efficient ultraviolet generation at 355 nm in LiB(3)O(5).
AB  - Highly efficient generation of UV radiation at 355 nm has been achieved in a
      LiB(3)O(5) crystal through the frequency mixing of the fundamental and second
      harmonic radiation of a Nd:YAG laser. An energy conversion efficiency of 60% has
      been obtained under the experimental conditions described here. Thus the
      usefulness of LiB(3)O(5) for frequency-conversion applications is demonstrated.

PMID- 19753064
TI  - All-optical power-controlled switching in four-wave mixing.
AB  - The use of four-wave mixing as an all-optical switching device is described. The
      switching process involves strong pump depletion and results from large-signal
      interactions. Interesting relationships among the input, the optical control, and
      the output signals and the parameters of the nonlinear medium are identified.

PMID- 19753065
TI  - Fiber-optic wavelength-division multiplexing and demultiplexing using volume
      holographic gratings.
AB  - We present theoretical and experimental results of a novel fiber-optic wavelength
      division multiplexing (WDM) design employing a broadband (>150-nm) dichromated
      gelatin volume holographic grating operating in a reflective Littrow
      configuration with on-axis optics, a single lens, and one fiber array. This
      configuration can achieve better than -1.5-dB insertion loss and -40-dB cross
      talk for a 6-channel system and -2.5-dB insertion loss and -20-dB cross talk for
      a 12-channel system with 15-nm channel spacing. For an experimental 4-channel WDM
      unit we measured better than -1.5-dB insertion loss for all channels and less
      than -32-dB cross talk. This design can provide cost and performance benefits for
      local area network communication applications.

PMID- 19753066
TI  - Three-dimensional blood vessel reconstruction by simulated annealing.
AB  - Simulated annealing, a Monte Carlo-like algorithm, is applied to three
      dimensional blood vessel reconstruction based on digital subtraction angiography.
      Since imaging systems often employ an insufficient number of projections,
      adequate reconstruction from observed data is not possible. It is shown that even
      in such cases objects can be sufficiently reconstructed by simulated annealing,
      which makes use of constraints based on a priori knowledge. This method is
      successfully demonstrated with a fundamental computer simulation.

PMID- 19753067
TI  - High-resolution imaging of the living human fovea: measurement of the intercenter
      cone distance by speckle interferometry.
AB  - A high-resolution method that allows direct measurements of the intercenter cone
      distance in the living human fovea is proposed. The experimental technique is
      similar to that used in stellar speckle interferometry. It is based on the
      recording and posterior processing of coherent short-exposure images of a small
      area of the central fovea. By using this optical-digital procedure, we have
      obtained what are to our knowledge the first objective measurements in vivo of
      the cone spacing in the human fovea. The reconstruction of the whole spatial
      information of the cone mosaic would also be possible by further improvements of
      the technique by subsequent application of image-reconstruction algorithms.

PMID- 19753068
TI  - Phase-gradient algorithm as an optimal estimator of the phase derivative.
AB  - The phase-gradient algorithm represents a powerful new signal-processing
      technique with applications to aperture-synthesis imaging. These include, for
      example, synthetic-aperture-radar phase correction and stellar-image
      reconstruction. The algorithm combines redundant information present in the data
      to arrive at an estimate of the phase derivative. We show that the estimator is
      in fact a linear, minimum-variance estimator of the phase derivative.

PMID- 19753069
TI  - Two-dimensional phase correction of synthetic-aperture-radar imagery.
AB  - A two-dimensional synthetic-aperture-radar (SAR) phase-correction algorithm is
      described as a natural extension of a one-dimensional technique developed
      previously. It embodies some similarities of phase-gradient speckle imaging and
      incorporates improvements in phase estimation. Diffraction-limited performance
      has been obtained on actual SAR imagery regardless of scene content or phase
      error structure. The algorithm is computationally efficient, robust, and easily
      implemented on a general-purpose computer or special-purpose hardware.

PMID- 19753070
TI  - Direct phase estimation from phase differences using fast elliptic partial
      differential equation solvers.
AB  - Obtaining robust phase estimates from phase differences is a problem common to
      several areas of importance to the optics and signal-processing communities.
      Specific areas of application include speckle imaging and interferometry,
      adaptive optics, compensated imaging, and coherent imaging such as synthetic
      aperture radar. We derive in a concise form the equations describing the phase
      estimation problem, relate these equations to the general form of elliptic
      partial differential equations, and illustrate results of reconstructions on
      large M by N grids, using existing, published, and readily available FORTRAN
      subroutines.

PMID- 19753071
TI  - Quantum statistics of broadband squeezed light.
AB  - Photon-emission sequences in nonclassical light beams generated by an optical
      parametric oscillator are studied. Exact photon-counting and waiting time
      distributions are derived by using a generating function technique based on the
      positive-P representation. This approach is used to present a simple physical
      picture of photon emissions from this nonclassical light source.

PMID- 19753072
TI  - Ultrahigh-intensity KrF* laser system.
AB  - The operational characteristics of an ultrahigh-intensity subpicosecond large
      aperture KrF* laser system are described. Measurements show the achievement of a
      focal spot diameter of less than 1.7 microm. Combined with measurements of the
      pulse width and pulse energy, this yields an average intensity of ~2 x 10(19)
      W/cm(2), a value corresponding to a peak electric field of ~24 (e/a(0)(2)). Light
      sources of this nature will find application in a broad range of studies of the
      nonlinear properties of matter in the strong-field regime.

PMID- 19753073
TI  - Widely tunable single-longitudinal-mode pulsed dye laser.
AB  - We have developed a simple cavity-length-stabilization method appropriate for
      single-longitudinal-mode pulsed lasers that use grazing-incidence gratings. Our
      technique relies on the detection of aminute (<0.5-mrad) angular variation in the
      output beam direction caused by a detuning betweenthe cavity-mode frequency and
      the center frequency of the grating passband. In a prototype systemimplementing
      this stabilization scheme we have generated single-longitudinal-mode scans of up
      to 290cm(-1).

PMID- 19753074
TI  - Interferential mode locking: Gaussian pulse analysis.
AB  - A simple analysis of the interference between two Gaussian pulses is presented.
      It is shown that the resulting pulse may be shorter than the initial ones if the
      interference phase is properly adjusted. The compression effect results from the
      difference of the durations of the interfering pulses and from their phase
      modulation. This mechanism may be implemented in mode-locked lasers, eitherby
      adjunction of a coupled cavity or use of a pulse-shaping Michelson interferometer
      as the outputcoupler. Gain-bandwidth-limited pulses may then be obtained. The
      model provides analytical expressions for pulse duration.

PMID- 19753075
TI  - Soliton generation through Raman amplification of noise bursts.
AB  - Operating in a high-gain regime, solitons with durations of the order of 600 fsec
      have been generated through the synchronous Raman amplification of noise bursts
      with durations of the order of 100psec and inverse bandwidths in the regime of
      the generated solitons.

PMID- 19753076
TI  - Femtosecond passively mode-locked Ti:Al(2)O(3) laser with a nonlinear external
      cavity.
AB  - Ultrashort pulses are generated in a Ti:Al(2)O(3) laser by using a coupled
      nonlinear external cavity. The external cavity uses self-phase modulation in an
      optical fiber to achieve passive mode locking without the need for synchronous
      pumping or acousto-optic modulation. A stable train of chirped 1.4-psec pulses is
      generated. After dispersive compensation, pulses as short as 200 fsec are
      obtained.

PMID- 19753077
TI  - Terahertz time-domain spectroscopy of water vapor.
AB  - We describe the application of a new high-brightness, terahertz-beam system to
      time-domain spectroscopy. By analyzing the propagation of terahertz
      electromagnetic pulses through water vapor, we have made what we believe are the
      most accurate measurements to date of the absorption cross sections of the water
      molecule for the nine strongest lines in the frequency range from 0.2 to 1.45
      THz.

PMID- 19753078
TI  - High-resolution nonlinear laser spectroscopy of room-temperature GaAs quantum
      well structures: observation of interference effects.
AB  - We describe frequency-domain four-wave mixing spectroscopy measurements near the
      fundamental band edge in room-temperature GaAs multiple quantum wells. The line
      shape information gives a measure of the dynamical behavior of the material and
      what is to our knowledge the first observation of an interference line shape due
      to a dominant slow contribution to the nonlinear response.

PMID- 19753079
TI  - Efficient, single-axial-mode operation of a monolithic MgO:LiNbO(3) optical
      parametric oscillator.
AB  - A monolithic doubly resonant optical parametric oscillator (OPO) fabricated from
      MgO:LiNbO(3) was pumped by a cw, frequency-doubled, diode-laser-pumped Nd:YAG
      laser. The threshold for cw operation was 12 mW, and pump depletions of up to 78%
      were observed two times above threshold. The total OPO output power was 8.15 mW,
      with a conversion efficiency for the incident pump of 34% and combined conversion
      efficiency for the 1064-nm laser light of 14%. The OPO was temperature tuned from
      1007 to 1129 nm, operated on a single-axial-mode pair over most of the range, and
      could be electric field tuned by as much as 38 nm near degeneracy.

PMID- 19753080
TI  - Anomalous-dispersion phase-matched second-harmonic generation.
AB  - We have demonstrated anomalous-dispersion phase-matched second-harmonic
      generation, using electric-field-induced second-harmonic generation in a liquid
      solution of Foron Brilliant Blue S-R (FBB). This dye has a sharp absorption
      maximum near 620 nm and a deep absorption minimum near 450 nm. The microscopic
      hyperpolarizability (beta) of FBB was measured at 1.58 and 0.954 microm and was
      found to be 163 x 10(-30) and -118 x 10(-30) cm(5)/esu, respectively. The change
      in sign of beta and the observation that beta(0), a frequency-independent measure
      of hyperpolarizability, is the same at both frequencies demonstrate the validity
      of the two-state model of the second-order hyperpolarizability.

PMID- 19753081
TI  - Two-photon absorption as a limitation to all-optical switching.
AB  - Two-photon absorption can place a fundamental limitation on waveguide all-optical
      switching devices. We have derived a general criterion to describe this
      limitation that must be satisfied by all materials. As a specific example, we
      have experimentally evaluated this criterion for a lead-glass fiber.

PMID- 19753082
TI  - Modes of nonlinear couplers: building blocks for physical insight.
AB  - The physics of nonlinear couplers is dictated by its normal modes, modes that are
      found from linear (axially uniform) couplers. Elementary power-flow arguments
      establish whether the mode is stable or unstable. These facts provide the
      bifurcation diagram that fully characterizes nonlinear coupling.

PMID- 19753083
TI  - Description of nonlinear couplers by power conservation.
AB  - Poynting's vector theorem describes power flow on twin-core couplers with
      arbitrary axial perturbations, both linear and nonlinear. This bypasses the
      coupled amplitude formulation and unifies nonlinear two-mode interactions in
      general.

PMID- 19753084
TI  - Simple method for analyzing the birefringence of an elliptical-core fiber by an
      equivalent rectangular waveguide.
AB  - We present details of a simple method, incorporating first-order perturbation
      theory, to analyze the birefringence exhibited by elliptical-core fibers by using
      an equivalent rectangular-core waveguide. The results from this method are
      compared with those obtained from the finite-element and another approximate
      technique to demonstrate the accuracy of this simple method. The method may be
      extended to analyze waveguides of arbitrary geometry.

PMID- 19753085
TI  - Sagnac interferometer for underwater sound detection: noise properties.
AB  - The use of a Sagnac interferometer as an acoustic sensor is discussed. Compared
      with a Mach-Zehnder interferometer it has the advantage of zero path-length
      difference. The sensitivity for low frequencies is shown to be proportional to
      frequency. With a passive homodyne-detection scheme using a 3 x 3 directional
      coupler, we report a noise-equivalent phase shift of 2.5 x 10(-7) rad/ radicalHz
      at 10 kHz. The detectivity is believed to be limited by backscattered light.

PMID- 19753086
TI  - Practical fiber-optic-based submicro-g accelerometer free from source and
      environmental perturbations.
AB  - We describe a novel accelerometer in which the sensing element is a weighted
      diaphragm designed to have minimal cross coupling. The displacement of the
      diaphragm, produced by acceleration, is measured by using two miniature
      hemispherical air-spaced Fabry-Perot interferometers, one constructed on either
      side of the diaphragm. The output of the two interferometers is processed such
      that the detrimental effects caused by wavelength drift of the source and
      variation in temperature of the sensor are reduced by 45.8 and 27.3 dB,
      respectively, compared with those of a single interferometer.

PMID- 19753087
TI  - Walking toward a convergence in aging research.

PMID- 19753088
TI  - How Precise is the Timing of Action Potentials?

PMID- 19753089
TI  - Cross-frequency coupling in parieto-frontal oscillatory networks during motor
      imagery revealed by magnetoencephalography.

PMID- 19753090
TI  - Overlapping areas of neuronal activation after motor and mental imagery training.

PMID- 19753091
TI  - The emotional consequences of being distracted.

PMID- 19753092
TI  - Bursts generate a non-reducible spike-pattern code.
AB  - At the single-neuron level, precisely timed spikes can either constitute firing
      rate codes or spike-pattern codes that utilize the relative timing between
      consecutive spikes. There has been little experimental support for the hypothesis
      that such temporal patterns contribute substantially to information transmission.
      By using grasshopper auditory receptors as a model system, we show that
      correlations between spikes can be used to represent behaviorally relevant
      stimuli. The correlations reflect the inner structure of the spike train: a
      succession of burst-like patterns. We demonstrate that bursts with different
      spike counts encode different stimulus features, such that about 20% of the
      transmitted information corresponds to discriminating between different features,
      and the remaining 80% is used to allocate these features in time. In this spike
      pattern code, the what and the when of the stimuli are encoded in the duration of
      each burst and the time of burst onset, respectively. Given the ubiquity of burst
      firing, we expect similar findings also for other neural systems.

PMID- 19753093
TI  - KF-1 Ubiquitin Ligase: An Anxiety Suppressor.
AB  - Anxiety is an instinct that may have developed to promote adaptive survival by
      evading unnecessary danger. However, excessive anxiety is disruptive and can be a
      basic disorder of other psychiatric diseases such as depression. The KF-1, a
      ubiquitin ligase located on the endoplasmic reticulum (ER), may prevent excessive
      anxiety; kf-1(-/-) mice exhibit selectively elevated anxiety-like behavior
      against light or heights. It is surmised that KF-1 degrades some target proteins,
      responsible for promoting anxiety, through the ER-associated degradation pathway,
      similar to Parkin in Parkinson's disease (PD). Parkin, another ER-ubiquitin
      ligase, prevents the degeneration of dopaminergic neurons by degrading the target
      proteins responsible for PD. Molecular phylogenetic studies have revealed that
      the prototype of kf-1 appeared in the very early phase of animal evolution but
      was lost, unlike parkin, in the lineage leading up to Drosophila. Therefore, kf
      1(-/-) mice may be a powerful tool for elucidating the molecular mechanisms
      involved in emotional regulation, and for screening novel
      anxiolytic/antidepressant compounds.

PMID- 19753094
TI  - Double Trouble? Potential for Hyperexcitability Following Both Channelopathic up-
      and Downregulation of I(h) in Epilepsy.
AB  - Studies of pathological ion channel regulation as an underlying mechanism of
      epilepsy have revealed alterations in the h-current in several animal models.
      While earlier reports indicate that downregulation of the h-current is pro
      excitatory on the single neuron level, we found an upregulation of I(h) in
      hyperexcitable CA1 pyramidal neuron dendrites following experimental febrile
      seizures. In addition, in several CA1 pyramidal neuron computational models of
      different complexity, h-current upregulation has been shown to lead to pro
      excitable effects. This focused review examines the complex impact of altered h
      current on neuronal resting membrane potential (RMP) and input resistance
      (R(in)), as well as reported interactions with other ionic conductances.

PMID- 19753095
TI  - Left temporal lobe structural and functional abnormality underlying auditory
      hallucinations in schizophrenia.
AB  - In this article, we have reviewed recent findings from our laboratory, originally
      presented in Hugdahl et al. (2008). These findings reveal that auditory
      hallucinations in schizophrenia should best be conceptualized as internally
      generated speech mis-representations lateralized to the left superior temporal
      gyrus and sulcus, not cognitively suppressed due to enhanced attention to the
      'voices' and failure of fronto-parietal executive control functions. An overview
      of diagnostic questionnaires for scoring of symptoms is presented together with a
      review of behavioral, structural, and functional MRI data. Functional imaging
      data have either shown increased or decreased activation depending on whether
      patients have been presented an external stimulus during scanning. Structural
      imaging data have shown reduction of grey matter density and volume in the same
      areas in the temporal lobe. We have proposed a model for the understanding of
      auditory hallucinations that trace the origin of auditory hallucinations to
      neuronal abnormality in the speech areas in the left temporal lobe, which is not
      suppressed by volitional cognitive control processes, due to dysfunctional fronto
      parietal executive cortical networks.

PMID- 19753096
TI  - Fluid reasoning and the developing brain.
AB  - Fluid reasoning is the cornerstone of human cognition, both during development
      and in adulthood. Despite this, the neural mechanisms underlying the development
      of fluid reasoning are largely unknown. In this review, we provide an overview of
      this important cognitive ability, the method of measurement, its changes over the
      childhood and adolescence of an individual, and its underlying neurobiological
      underpinnings. We review important findings from psychometric, cognitive, and
      neuroscientific literatures, and outline important future directions for this
      interdisciplinary research.

PMID- 19753097
TI  - Virtual reality and the role of the prefrontal cortex in adults and children.
AB  - In this review, the neural underpinnings of the experience of presence are
      outlined. Firstly, it is shown that presence is associated with activation of a
      distributed network, which includes the dorsal and ventral visual stream, the
      parietal cortex, the premotor cortex, mesial temporal areas, the brainstem and
      the thalamus. Secondly, the dorsolateral prefrontal cortex (DLPFC) is identified
      as a key node of the network as it modulates the activity of the network and the
      associated experience of presence. Thirdly, children lack the strong modulatory
      influence of the DLPFC on the network due to their unmatured frontal cortex.
      Fourthly, it is shown that presence-related measures are influenced by
      manipulating the activation in the DLPFC using transcranial direct current
      stimulation (tDCS) while participants are exposed to the virtual roller coaster
      ride. Finally, the findings are discussed in the context of current models
      explaining the experience of presence, the rubber hand illusion, and out-of-body
      experiences.

PMID- 19753098
TI  - Ontologies for Neuroscience: What are they and What are they Good for?
AB  - Current information technology practices in neuroscience make it difficult to
      understand the organization of the brain across spatial scales. Subcellular
      junctional connectivity, cytoarchitectural local connectivity, and long-range
      topographical connectivity are just a few of the relevant data domains that must
      be synthesized in order to make sense of the brain. However, due to the
      heterogeneity of the data produced within these domains, the landscape of
      multiscale neuroscience data is fragmented. A standard framework for neuroscience
      data is needed to bridge existing digital data resources and to help in the
      conceptual unification of the multiple disciplines of neuroscience. Using our
      efforts in building ontologies for neuroscience as an example, we examine the
      benefits and limits of ontologies as a solution for this data integration
      problem. We provide several examples of their application to problems of image
      annotation, content-based retrieval of structural data, and integration of data
      across scales and researchers.

PMID- 19753099
TI  - Function of Ca(2+) release channels in Purkinje cells that survive in the
      infarcted canine heart: a mechanism for triggered Purkinje ectopy.
AB  - BACKGROUND: Triggered Purkinje ectopy can lead to the initiation of serious
      ventricular arrhythmias in post-myocardial infarction patients. In the canine
      model, Purkinje cells from the subendocardial border of the healing infarcted
      heart can initiate ventricular arrhythmias. Intracellular Ca(2+) abnormalities
      underlie these arrhythmias, yet the subcellular reasons for these abnormalities
      remain unknown. METHODS AND RESULTS: Using 2D confocal microscopy, we directly
      quantify and compare typical spontaneous Ca(2+) events in specific subcellular
      regions of normal Purkinje cells with those Purkinje cells from the
      subendocardium of the 48-hour infarcted canine heart (IZPCs). The Ca(2+) event
      rate was higher in the subsarcolemmal region of IZPCs when compared with normal
      Purkinje cells; IZPC amplitudes were higher, yet the spatial extents of these
      events were similar. The amplitude of caffeine-releasable Ca(2+) in either the
      subsarcolemmal or core regions of IZPCs did not differ from normal Purkinje
      cells, suggesting that Ca(2+) overload was not related to the frequency change.
      In permeabilized Purkinje cells from both groups, the event rate was related to
      free [Ca(2+)] in both subsarcolemmal and core, but in IZPCs, this event rate was
      significantly increased at each free Ca(2+), suggesting an enhanced sensitivity
      to Ca(2+) release. Furthermore, decays of wide long lasting Ca(2+) release events
      in IZPC's core were significantly accelerated compared with those in normal
      Purkinje cells. JTV519 (K201) suppressed IZPC cell wide Ca(2+) waves as well as
      normalized the enhanced event rate and its response to free Ca(2+). CONCLUSIONS:
      Increased spontaneous Ca(2+) release events in IZPCs are due to uniform
      regionally increased Ca(2+) release channel sensitivity to Ca(2+) without a
      change in sarcoplasmic reticulum content. In addition, Ca(2+) reuptake in IZPCs
      is accelerated. These properties would lower the threshold of Ca(2+) release
      channels, setting the stage for the highly frequent arrhythmogenic cell wide
      Ca(2+) waves observed in IZPCs.

PMID- 19753100
TI  - Group IV phospholipase A(2)alpha controls the formation of inter-cisternal
      continuities involved in intra-Golgi transport.
AB  - The organization of intra-Golgi trafficking and the nature of the transport
      intermediates involved (e.g., vesicles, tubules, or tubular continuities) remain
      incompletely understood. It was recently shown that successive cisternae in the
      Golgi stack are interconnected by membrane tubules that form during the arrival
      of transport carriers from the endoplasmic reticulum. Here, we examine the
      mechanisms of generation and the function of these tubules. In principle, tubule
      formation might depend on several protein- and/or lipid-based mechanisms. Among
      the latter, we have studied the phospholipase A(2) (PLA(2))-mediated generation
      of wedge-shaped lysolipids, with the resulting local positive membrane curvature.
      We show that the arrival of cargo at the Golgi complex induces the recruitment of
      Group IVA Ca(2+)-dependent, cytosolic PLA(2) (cPLA(2)alpha) onto the Golgi
      complex itself, and that this cPLA(2)alpha is required for the formation of the
      traffic-dependent intercisternal tubules and for intra-Golgi transport. In
      contrast, silencing of cPLA(2)alpha has no inhibitory effects on peri-Golgi
      vesicles. These findings identify cPLA(2)alpha as the first component of the
      machinery that is responsible for the formation of intercisternal tubular
      continuities and support a role for these continuities in transport through the
      Golgi complex.

PMID- 19753101
TI  - Loss of mitogen-activated protein kinase kinase kinase 4 (MAP3K4) reveals a
      requirement for MAPK signalling in mouse sex determination.
AB  - Sex determination in mammals is controlled by the presence or absence of the Y
      linked gene SRY. In the developing male (XY) gonad, sex-determining region of the
      Y (SRY) protein acts to up-regulate expression of the related gene, SOX9, a
      transcriptional regulator that in turn initiates a downstream pathway of testis
      development, whilst also suppressing ovary development. Despite the requirement
      for a number of transcription factors and secreted signalling molecules in sex
      determination, intracellular signalling components functioning in this process
      have not been defined. Here we report a role for the phylogenetically ancient
      mitogen-activated protein kinase (MAPK) signalling pathway in mouse sex
      determination. Using a forward genetic screen, we identified the recessive
      boygirl (byg) mutation. On the C57BL/6J background, embryos homozygous for byg
      exhibit consistent XY gonadal sex reversal. The byg mutation is an A to T
      transversion causing a premature stop codon in the gene encoding MAP3K4 (also
      known as MEKK4), a mitogen-activated protein kinase kinase kinase. Analysis of XY
      byg/byg gonads at 11.5 d post coitum reveals a growth deficit and a failure to
      support mesonephric cell migration, both early cellular processes normally
      associated with testis development. Expression analysis of mutant XY gonads at
      the same stage also reveals a dramatic reduction in Sox9 and, crucially, Sry at
      the transcript and protein levels. Moreover, we describe experiments showing the
      presence of activated MKK4, a direct target of MAP3K4, and activated p38 in the
      coelomic region of the XY gonad at 11.5 d post coitum, establishing a link
      between MAPK signalling in proliferating gonadal somatic cells and regulation of
      Sry expression. Finally, we provide evidence that haploinsufficiency for Map3k4
      accounts for T-associated sex reversal (Tas). These data demonstrate that MAP3K4
      dependent signalling events are required for normal expression of Sry during
      testis development, and create a novel entry point into the molecular and
      cellular mechanisms underlying sex determination in mice and disorders of sexual
      development in humans.

PMID- 19753102
TI  - Genetic characterization of Venezuelan equine encephalitis virus from Bolivia,
      Ecuador and Peru: identification of a new subtype ID lineage.
AB  - Venezuelan equine encephalitis virus (VEEV) has been responsible for hundreds of
      thousands of human and equine cases of severe disease in the Americas. A passive
      surveillance study was conducted in Peru, Bolivia and Ecuador to determine the
      arboviral etiology of febrile illness. Patients with suspected viral-associated,
      acute, undifferentiated febrile illness of <7 days duration were enrolled in the
      study and blood samples were obtained from each patient and assayed by virus
      isolation. Demographic and clinical information from each patient was also
      obtained at the time of voluntary enrollment. In 2005-2007, cases of Venezuelan
      equine encephalitis (VEE) were diagnosed for the first time in residents of
      Bolivia; the patients did not report traveling, suggesting endemic circulation of
      VEEV in Bolivia. In 2001 and 2003, VEE cases were also identified in Ecuador.
      Since 1993, VEEV has been continuously isolated from patients in Loreto, Peru,
      and more recently (2005), in Madre de Dios, Peru. We performed phylogenetic
      analyses with VEEV from Bolivia, Ecuador and Peru and compared their
      relationships to strains from other parts of South America. We found that VEEV
      subtype ID Panama/Peru genotype is the predominant one circulating in Peru. We
      also demonstrated that VEEV subtype ID strains circulating in Ecuador belong to
      the Colombia/Venezuela genotype and VEEV from Madre de Dios, Peru and Cochabamba,
      Bolivia belong to a new ID genotype. In summary, we identified a new major
      lineage of enzootic VEEV subtype ID, information that could aid in the
      understanding of the emergence and evolution of VEEV in South America.

PMID- 19753103
TI  - Wolbachia infection reduces blood-feeding success in the dengue fever mosquito,
      Aedes aegypti.
AB  - BACKGROUND: The mosquito Aedes aegypti was recently transinfected with a life
      shortening strain of the endosymbiont Wolbachia pipientis (wMelPop) as the first
      step in developing a biocontrol strategy for dengue virus transmission. In
      addition to life-shortening, the wMelPop-infected mosquitoes also exhibit
      increased daytime activity and metabolic rates. Here we sought to quantify the
      blood-feeding behaviour of Wolbachia-infected females as an indicator of any
      virulence or energetic drain associated with Wolbachia infection.
      METHODOLOGY/PRINCIPAL FINDINGS: In a series of blood-feeding trials in response
      to humans, we have shown that Wolbachia-infected mosquitoes do not differ in
      their response time to humans, but that as they age they obtain fewer and smaller
      blood meals than Wolbachia-uninfected controls. Lastly, we observed a behavioural
      characteristic in the Wolbachia infected mosquitoes best described as a "bendy"
      proboscis that may explain the decreased biting success.
      CONCLUSIONS/SIGNIFICANCE: Taken together the evidence suggests that wMelPop
      infection may be causing tissue damage in a manner that intensifies with mosquito
      age and that leads to reduced blood-feeding success. These behavioural changes
      require further investigation with respect to a possible physiological mechanism
      and their role in vectorial capacity of the insect. The selective decrease of
      feeding success in older mosquitoes may act synergistically with other Wolbachia
      associated traits including life-shortening and viral protection in biocontrol
      strategies.

PMID- 19753104
TI  - Biphasic synaptic Ca influx arising from compartmentalized electrical signals in
      dendritic spines.
AB  - Excitatory synapses on mammalian principal neurons are typically formed onto
      dendritic spines, which consist of a bulbous head separated from the parent
      dendrite by a thin neck. Although activation of voltage-gated channels in the
      spine and stimulus-evoked constriction of the spine neck can influence synaptic
      signals, the contribution of electrical filtering by the spine neck to basal
      synaptic transmission is largely unknown. Here we use spine and dendrite calcium
      (Ca) imaging combined with 2-photon laser photolysis of caged glutamate to assess
      the impact of electrical filtering imposed by the spine morphology on synaptic Ca
      transients. We find that in apical spines of CA1 hippocampal neurons, the spine
      neck creates a barrier to the propagation of current, which causes a voltage drop
      and results in spatially inhomogeneous activation of voltage-gated Ca channels
      (VGCCs) on a micron length scale. Furthermore, AMPA and NMDA-type glutamate
      receptors (AMPARs and NMDARs, respectively) that are colocalized on individual
      spine heads interact to produce two kinetically and mechanistically distinct
      phases of synaptically evoked Ca influx. Rapid depolarization of the spine
      triggers a brief and large Ca current whose amplitude is regulated in a graded
      manner by the number of open AMPARs and whose duration is terminated by the
      opening of small conductance Ca-activated potassium (SK) channels. A slower phase
      of Ca influx is independent of AMPAR opening and is determined by the number of
      open NMDARs and the post-stimulus potential in the spine. Biphasic synaptic Ca
      influx only occurs when AMPARs and NMDARs are coactive within an individual
      spine. These results demonstrate that the morphology of dendritic spines endows
      associated synapses with specialized modes of signaling and permits the graded
      and independent control of multiple phases of synaptic Ca influx.

PMID- 19753105
TI  - Real lives and white lies in the funding of scientific research: the granting
      system turns young scientists into bureaucrats and then betrays them.

PMID- 19753106
TI  - Evaluating eHealth: undertaking robust international cross-cultural eHealth
      research.

PMID- 19753107
TI  - The GRADE system for rating clinical guidelines.

PMID- 19753108
TI  - Grading quality of evidence and strength of recommendations: a perspective.

PMID- 19753109
TI  - Effect of duration and intermittency of rifampin on tuberculosis treatment
      outcomes: a systematic review and meta-analysis.
AB  - BACKGROUND: Treatment regimens for active tuberculosis (TB) that are
      intermittent, or use rifampin during only the initial phase, offer practical
      advantages, but their efficacy has been questioned. We conducted a systematic
      review of treatment regimens for active TB, to assess the effect of duration and
      intermittency of rifampin use on TB treatment outcomes. METHODS AND FINDINGS:
      PubMed, Embase, and the Cochrane CENTRAL database for clinical trials were
      searched for randomized controlled trials, published in English, French, or
      Spanish, between 1965 and June 2008. Selected studies utilized standardized
      treatment with rifampin-containing regimens. Studies reported bacteriologically
      confirmed failure and/or relapse in previously untreated patients with
      bacteriologically confirmed pulmonary TB. Pooled cumulative incidences of
      treatment outcomes and association with risk factors were computed with
      stratified random effects meta-analyses. Meta-regression was performed using a
      negative binomial regression model. A total of 57 trials with 312 arms and 21,472
      participants were included in the analysis. Regimens utilizing rifampin only for
      the first 1-2 mo had significantly higher rates of failure, relapse, and acquired
      drug resistance, as compared to regimens that used rifampin for 6 mo. This was
      particularly evident when there was initial drug resistance to isoniazid,
      streptomycin, or both. On the other hand, there was little evidence of difference
      in failure or relapse with daily or intermittent schedules of treatment
      administration, although there was insufficient published evidence of the
      efficacy of twice-weekly rifampin administration throughout therapy. CONCLUSIONS:
      TB treatment outcomes were significantly worse with shorter duration of rifampin,
      or with initial drug resistance to isoniazid and/or streptomycin. Treatment
      outcomes were similar with all intermittent schedules evaluated, but there is
      insufficient evidence to support administration of treatment twice weekly
      throughout therapy.

PMID- 19753110
TI  - Polyparasite helminth infections and their association to anaemia and
      undernutrition in Northern Rwanda.
AB  - BACKGROUND: Intestinal schistosomiasis and soil-transmitted helminth (STH)
      infections constitute major public health problems in many parts of sub-Saharan
      Africa. In this study we examined the functional significance of such
      polyparasite infections in anemia and undernutrition in Rwandan individuals.
      METHODS: Three polyparasite infection profiles were defined, in addition to a
      reference profile that consisted of either no infections or low-intensity
      infection with only one of the focal parasite species. Logistic regression models
      were applied to data of 1,605 individuals from 6 schools in 2 districts of the
      Northern Province before chemotherapeutic treatment in order to correctly
      identify individuals who were at higher odds of being anaemic and/or
      undernourished. FINDINGS: Stunted relative to nonstunted, and males compared to
      females, were found to be at higher odds of being anaemic independently of
      polyparasite infection profile. The odds of being wasted were 2-fold greater for
      children with concurrent infection of at least 2 parasites at M+ intensity
      compared to those children with the reference profile. Males compared to females
      and anaemic compared to nonanaemic children were significantly more likely to be
      stunted. None of the three polyparasite infection profiles were found to have
      significant effects on stunting. CONCLUSION: The present data suggest that the
      levels of polyparasitism, and infection intensities in the Rwandan individuals
      examined here may be lower as compared to other recent similar epidemiological
      studies in different regions across sub-Saharan Africa. Neither the odds of
      anaemia nor the odds of stunting were found to be significantly different in the
      three-polyparasite infection profiles. However, the odds of wasting were higher
      in those children with at least two parasites at M+ intensity compared to those
      children with the reference profile. Nevertheless, despite the low morbidity
      levels indicated in the population under study here, we recommend sustainable
      efforts for the deworming of affected populations to be continued in order to
      support the economic development of the country.

PMID- 19753111
TI  - Dual energy X-Ray absorptiometry body composition reference values from NHANES.
AB  - In 2008 the National Center for Health Statistics released a dual energy x-ray
      absorptiometry (DXA) whole body dataset from the NHANES population-based sample
      acquired with modern fan beam scanners in 15 counties across the United States
      from 1999 through 2004. The NHANES dataset was partitioned by gender and
      ethnicity and DXA whole body measures of %fat, fat mass/height(2), lean
      mass/height(2), appendicular lean mass/height(2), %fat trunk/%fat legs ratio,
      trunk/limb fat mass ratio of fat, bone mineral content (BMC) and bone mineral
      density (BMD) were analyzed to provide reference values for subjects 8 to 85
      years old. DXA reference values for adults were normalized to age; reference
      values for children included total and sub-total whole body results and were
      normalized to age, height, or lean mass. We developed an obesity classification
      scheme by using estabbody mass index (BMI) classification thresholds and
      prevalences in young adults to generate matching classification thresholds for
      Fat Mass Index (FMI; fat mass/height(2)). These reference values should be
      helpful in the evaluation of a variety of adult and childhood abnormalities
      involving fat, lean, and bone, for establishing entry criteria into clinical
      trials, and for other medical, research, and epidemiological uses.

PMID- 19753112
TI  - The mitotic arrest deficient protein MAD2B interacts with the small GTPase RAN
      throughout the cell cycle.
AB  - BACKGROUND: Previously, we identified the mitotic arrest deficient protein MAD2B
      (MAD2L2) as a bona fide interactor of the renal cell carcinoma (RCC)-associated
      protein PRCC. In addition, we found that fusion of PRCC with the transcription
      factor TFE3 in t(X;1)(p11;q21)-positive RCCs results in an impairment of this
      interaction and, concomitantly, an abrogation of cell cycle progression. Although
      MAD2B is thought to inhibit the anaphase promoting complex (APC) by binding to
      CDC20 and/or CDH1(FZR1), its exact role in cell cycle control still remains to be
      established. METHODOLOGY/PRINCIPAL FINDINGS: Using a yeast two-hybrid interaction
      trap we identified the small GTPase RAN, a well-known cell cycle regulator, as a
      novel MAD2B binding protein. Endogenous interaction was established in mammalian
      cells via co-localization and co-immunoprecipitation of the respective proteins.
      The interaction domain of RAN could be assigned to a C-terminal moiety of 60
      amino acids, whereas MAD2B had to be present in its full-length conformation. The
      MAD2B-RAN interaction was found to persist throughout the cell cycle. During
      mitosis, co-localization at the spindle was observed. CONCLUSIONS/SIGNIFICANCE:
      The small GTPase RAN is a novel MAD2B binding protein. This novel protein-protein
      interaction may play a role in (i) the control over the spindle checkpoint during
      mitosis and (ii) the regulation of nucleocytoplasmic trafficking during
      interphase.

PMID- 19753113
TI  - Selective targeting of TRPV1 expressing sensory nerve terminals in the spinal
      cord for long lasting analgesia.
AB  - Chronic pain is a major clinical problem and opiates are often the only
      treatment, but they cause significant problems ranging from sedation to deadly
      respiratory depression. Resiniferatoxin (RTX), a potent agonist of Transient
      Receptor Potential Vanilloid 1 (TRPV1), causes a slow, sustained and irreversible
      activation of TRPV1 and increases the frequency of spontaneous excitatory
      postsynaptic currents, but causes significant depression of evoked EPSCs due to
      nerve terminal depolarization block. Intrathecal administration of RTX to rats in
      the short-term inhibits nociceptive synaptic transmission, and in the long-term
      causes a localized, selective ablation of TRPV1-expressing central sensory nerve
      terminals leading to long lasting analgesia in behavioral models. Since RTX
      actions are selective for central sensory nerve terminals, other efferent
      functions of dorsal root ganglion neurons can be preserved. Preventing
      nociceptive transmission at the level of the spinal cord can be a useful strategy
      to treat chronic, debilitating and intractable pain.

PMID- 19753114
TI  - Enterocyte shedding and epithelial lining repair following ischemia of the human
      small intestine attenuate inflammation.
AB  - BACKGROUND: Recently, we observed that small-intestinal ischemia and reperfusion
      was found to entail a rapid loss of apoptotic and necrotic cells. This study was
      conducted to investigate whether the observed shedding of ischemically damaged
      epithelial cells affects IR induced inflammation in the human small gut. METHODS
      AND FINDINGS: Using a newly developed IR model of the human small intestine, the
      inflammatory response was studied on cellular, protein and mRNA level. Thirty
      patients were consecutively included. Part of the jejunum was subjected to 30
      minutes of ischemia and variable reperfusion periods (mean reperfusion time 120
      (+/-11) minutes). Ethical approval and informed consent were obtained. Increased
      plasma intestinal fatty acid binding protein (I-FABP) levels indicated loss in
      epithelial cell integrity in response to ischemia and reperfusion (p<0.001 vs
      healthy). HIF-1alpha gene expression doubled (p = 0.02) and C3 gene expression
      increased 4-fold (p = 0.01) over the course of IR. Gut barrier failure, assessed
      as LPS concentration in small bowel venous effluent blood, was not observed (p =
      0.18). Additionally, mRNA expression of HO-1, IL-6, IL-8 did not alter. No
      increased expression of endothelial adhesion molecules, TNFalpha release,
      increased numbers of inflammatory cells (p = 0.71) or complement activation,
      assessed as activated C3 (p = 0.14), were detected in the reperfused tissue.
      CONCLUSIONS: In the human small intestine, thirty minutes of ischemia followed by
      up to 4 hours of reperfusion, does not seem to lead to an explicit inflammatory
      response. This may be explained by a unique mechanism of shedding of damaged
      enterocytes, reported for the first time by our group.

PMID- 19753115
TI  - Characterization of an enantioselective odorant receptor in the yellow fever
      mosquito Aedes aegypti.
AB  - Enantiomers differ only in the left or right handedness (chirality) of their
      orientations and exhibit identical chemical and physical properties. In chemical
      communication systems, enantiomers can be differentially active at the
      physiological and behavioral levels. Only recently were enantioselective odorant
      receptors demonstrated in mammals while their existence in insects has remained
      hypothetical. Using the two-microelectrode voltage clamp of Xenopus oocytes, we
      show that the yellow fever mosquito, Aedes aegypti, odorant receptor 8 (AaOR8)
      acts as a chiral selective receptor for the (R)-(-)-enantiomer of 1-octen-3-ol,
      which in the presence of other kairomones is an attractant used by blood-sucking
      insects to locate their hosts. In addition to steric constraints, chain length
      and degree of unsaturation play important roles in this recognition process. This
      is the first characterization of an enantioselective odorant receptor in insects
      and the results demonstrate that an OR alone, without helper proteins, can
      account for chiral specificity exhibited by olfactory sensory neurons (OSNs).

PMID- 19753116
TI  - Application of a mathematical model to describe the effects of chlorpyrifos on
      Caenorhabditis elegans development.
AB  - BACKGROUND: The nematode Caenorhabditis elegans is being assessed as an
      alternative model organism as part of an interagency effort to develop better
      means to test potentially toxic substances. As part of this effort, assays that
      use the COPAS Biosort flow sorting technology to record optical measurements
      (time of flight (TOF) and extinction (EXT)) of individual nematodes under various
      chemical exposure conditions are being developed. A mathematical model has been
      created that uses Biosort data to quantitatively and qualitatively describe C.
      elegans growth, and link changes in growth rates to biological events.
      Chlorpyrifos, an organophosphate pesticide known to cause developmental delays
      and malformations in mammals, was used as a model toxicant to test the
      applicability of the growth model for in vivo toxicological testing.
      METHODOLOGY/PRINCIPAL FINDINGS: L1 larval nematodes were exposed to a range of
      sub-lethal chlorpyrifos concentrations (0-75 microM) and measured every 12 h. In
      the absence of toxicant, C. elegans matured from L1s to gravid adults by 60 h. A
      mathematical model was used to estimate nematode size distributions at various
      times. Mathematical modeling of the distributions allowed the number of measured
      nematodes and log(EXT) and log(TOF) growth rates to be estimated. The model
      revealed three distinct growth phases. The points at which estimated growth rates
      changed (change points) were constant across the ten chlorpyrifos concentrations.
      Concentration response curves with respect to several model-estimated quantities
      (numbers of measured nematodes, mean log(TOF) and log(EXT), growth rates, and
      time to reach change points) showed a significant decrease in C. elegans growth
      with increasing chlorpyrifos concentration. CONCLUSIONS: Effects of chlorpyrifos
      on C. elegans growth and development were mathematically modeled. Statistical
      tests confirmed a significant concentration effect on several model endpoints.
      This confirmed that chlorpyrifos affects C. elegans development in a
      concentration dependent manner. The most noticeable effect on growth occurred
      during early larval stages: L2 and L3. This study supports the utility of the C.
      elegans growth assay and mathematical modeling in determining the effects of
      potentially toxic substances in an alternative model organism using high
      throughput technologies.

PMID- 19753117
TI  - Overexpression of transcription factor Sp1 leads to gene expression perturbations
      and cell cycle inhibition.
AB  - BACKGROUND: The ubiquitous transcription factor Sp1 regulates the expression of a
      vast number of genes involved in many cellular functions ranging from
      differentiation to proliferation and apoptosis. Sp1 expression levels show a
      dramatic increase during transformation and this could play a critical role for
      tumour development or maintenance. Although Sp1 deregulation might be beneficial
      for tumour cells, its overexpression induces apoptosis of untransformed cells.
      Here we further characterised the functional and transcriptional responses of
      untransformed cells following Sp1 overexpression. METHODOLOGY AND PRINCIPAL
      FINDINGS: We made use of wild-type and DNA-binding-deficient Sp1 to demonstrate
      that the induction of apoptosis by Sp1 is dependent on its capacity to bind DNA.
      Genome-wide expression profiling identified genes involved in cancer, cell death
      and cell cycle as being enriched among differentially expressed genes following
      Sp1 overexpression. In silico search to determine the presence of Sp1 binding
      sites in the promoter region of modulated genes was conducted. Genes that
      contained Sp1 binding sites in their promoters were enriched among down-regulated
      genes. The endogenous sp1 gene is one of the most down-regulated suggesting a
      negative feedback loop induced by overexpressed Sp1. In contrast, genes
      containing Sp1 binding sites in their promoters were not enriched among up
      regulated genes. These results suggest that the transcriptional response involves
      both direct Sp1-driven transcription and indirect mechanisms. Finally, we show
      that Sp1 overexpression led to a modified expression of G1/S transition
      regulatory genes such as the down-regulation of cyclin D2 and the up-regulation
      of cyclin G2 and cdkn2c/p18 expression. The biological significance of these
      modifications was confirmed by showing that the cells accumulated in the G1 phase
      of the cell cycle before the onset of apoptosis. CONCLUSION: This study shows
      that the binding to DNA of overexpressed Sp1 induces an inhibition of cell cycle
      progression that precedes apoptosis and a transcriptional response targeting
      genes containing Sp1 binding sites in their promoter or not suggesting both
      direct Sp1-driven transcription and indirect mechanisms.

PMID- 19753118
TI  - Cellular and behavioral effects of cranial irradiation of the subventricular zone
      in adult mice.
AB  - BACKGROUND: In mammals, new neurons are added to the olfactory bulb (OB)
      throughout life. Most of these new neurons, granule and periglomerular cells
      originate from the subventricular zone (SVZ) lining the lateral ventricles and
      migrate via the rostral migratory stream toward the OB. Thousands of new neurons
      appear each day, but the function of this ongoing neurogenesis remains unclear.
      METHODOLOGY/PRINCIPAL FINDINGS: In this study, we irradiated adult mice to impair
      constitutive OB neurogenesis, and explored the functional impacts of this
      irradiation on the sense of smell. We found that focal irradiation of the SVZ
      greatly decreased the rate of production of new OB neurons, leaving other brain
      areas intact. This effect persisted for up to seven months after exposure to 15
      Gray. Despite this robust impairment, the thresholds for detecting pure odorant
      molecules and short-term olfactory memory were not affected by irradiation.
      Similarly, the ability to distinguish between odorant molecules and the odorant
      guided social behavior of irradiated mice were not affected by the decrease in
      the number of new neurons. Only long-term olfactory memory was found to be
      sensitive to SVZ irradiation. CONCLUSION/SIGNIFICANCE: These findings suggest
      that the continuous production of adult-generated neurons is involved in
      consolidating or restituting long-lasting olfactory traces.

PMID- 19753119
TI  - Identification of nucleases and phosphatases by direct biochemical screen of the
      Saccharomyces cerevisiae proteome.
AB  - The availability of yeast strain collections expressing individually tagged
      proteins to facilitate one-step purification provides a powerful approach to
      identify proteins with particular biochemical activities. To identify novel exo-
      and endo-nucleases that might function in DNA repair, we undertook a proteomic
      screen making use of the movable ORF (MORF) library of yeast expression plasmids.
      This library consists of 5,854 yeast strains each expressing a unique yeast ORF
      fused to a tripartite tag consisting of His(6), an HA epitope, a protease 3C
      cleavage site, and the IgG-binding domain (ZZ) from protein A, under the control
      of the GAL1 promoter for inducible expression. Pools of proteins were partially
      purified on IgG sepharose and tested for nuclease activity using three different
      radiolabeled DNA substrates. Several known nucleases and phosphatases were
      identified, as well as two new members of the histidine phosphatase superfamily,
      which includes phosphoglycerate mutases and phosphatases. Subsequent
      characterization revealed YDR051c/Det1 to be an acid phosphatase with broad
      substrate specificity, whereas YOR283w has a broad pH range and hydrolyzes
      hydrophilic phosphorylated substrates. Although no new nuclease activities were
      identified from this screen, we did find phosphatase activity associated with a
      protein of unknown function, YOR283w, and with the recently characterized protein
      Det1. This knowledge should guide further genetic and biochemical
      characterization of these proteins.

PMID- 19753120
TI  - Eye-hand coordination during dynamic visuomotor rotations.
AB  - BACKGROUND: for many technology-driven visuomotor tasks such as tele-surgery,
      human operators face situations in which the frames of reference for vision and
      action are misaligned and need to be compensated in order to perform the tasks
      with the necessary precision. The cognitive mechanisms for the selection of
      appropriate frames of reference are still not fully understood. This study
      investigated the effect of changing visual and kinesthetic frames of reference
      during wrist pointing, simulating activities typical for tele-operations.
      METHODS: using a robotic manipulandum, subjects had to perform center-out
      pointing movements to visual targets presented on a computer screen, by
      coordinating wrist flexion/extension with abduction/adduction. We compared
      movements in which the frames of reference were aligned (unperturbed condition)
      with movements performed under different combinations of visual/kinesthetic
      dynamic perturbations. The visual frame of reference was centered to the computer
      screen, while the kinesthetic frame was centered around the wrist joint. Both
      frames changed their orientation dynamically (angular velocity = 36 degrees /s)
      with respect to the head-centered frame of reference (the eyes). Perturbations
      were either unimodal (visual or kinesthetic), or bimodal (visual+kinesthetic). As
      expected, pointing performance was best in the unperturbed condition. The spatial
      pointing error dramatically worsened during both unimodal and most bimodal
      conditions. However, in the bimodal condition, in which both disturbances were in
      phase, adaptation was very fast and kinematic performance indicators approached
      the values of the unperturbed condition. CONCLUSIONS: this result suggests that
      subjects learned to exploit an "affordance" made available by the invariant phase
      relation between the visual and kinesthetic frames. It seems that after detecting
      such invariance, subjects used the kinesthetic input as an informative signal
      rather than a disturbance, in order to compensate the visual rotation without
      going through the lengthy process of building an internal adaptation model.
      Practical implications are discussed as regards the design of advanced, high
      performance man-machine interfaces.

PMID- 19753121
TI  - A quantitative method to analyze Drosophila pupal eye patterning.
AB  - BACKGROUND: The Drosophila pupal eye has become a popular paradigm for
      understanding morphogenesis and tissue patterning. Correct rearrangement of cells
      between ommatidia is required to organize the ommatidial array across the eye
      field. This requires cell movement, cell death, changes to cell-cell adhesion,
      signaling and fate specification. METHODOLOGY: We describe a method to
      quantitatively assess mis-patterning of the Drosophila pupal eye and objectively
      calculate a 'mis-patterning score' characteristic of a specific genotype. This
      entails step-by-step scoring of specific traits observed in pupal eyes dissected
      40-42 hours after puparium formation and subsequent statistical analysis of this
      data. SIGNIFICANCE: This method provides an unbiased quantitative score of mis
      patterning severity that can be used to compare the impact of different genetic
      mutations on tissue patterning.

PMID- 19753122
TI  - Analysis of SNPs and haplotypes in vitamin D pathway genes and renal cancer risk.
AB  - In the kidney vitamin D is converted to its active form. Since vitamin D exerts
      its activity through binding to the nuclear vitamin D receptor (VDR), most
      genetic studies have primarily focused on variation within this gene. Therefore,
      analysis of genetic variation in VDR and other vitamin D pathway genes may
      provide insight into the role of vitamin D in renal cell carcinoma (RCC)
      etiology. RCC cases (N = 777) and controls (N = 1,035) were genotyped to
      investigate the relationship between RCC risk and variation in eight target
      genes. Minimum-p-value permutation (Min-P) tests were used to identify genes
      associated with risk. A three single nucleotide polymorphism (SNP) sliding window
      was used to identify chromosomal regions with a False Discovery Rate of <10%,
      where subsequently, haplotype relative risks were computed in Haplostats. Min-P
      values showed that VDR (p-value = 0.02) and retinoid-X-receptor-alpha (RXRA) (p
      value = 0.10) were associated with RCC risk. Within VDR, three haplotypes across
      two chromosomal regions of interest were identified. The first region, located
      within intron 2, contained two haplotypes that increased RCC risk by
      approximately 25%. The second region included a haplotype (rs2239179, rs12717991)
      across intron 4 that increased risk among participants with the TC (OR = 1.31,
      95% CI = 1.09-1.57) haplotype compared to participants with the common haplotype,
      TT. Across RXRA, one haplotype located 3' of the coding sequence (rs748964,
      rs3118523), increased RCC risk 35% among individuals with the variant haplotype
      compared to those with the most common haplotype. This study comprehensively
      evaluated genetic variation across eight vitamin D pathway genes in relation to
      RCC risk. We found increased risk associated with VDR and RXRA. Replication
      studies are warranted to confirm these findings.

PMID- 19753123
TI  - Optimizing Taq polymerase concentration for improved signal-to-noise in the broad
      range detection of low abundance bacteria.
AB  - BACKGROUND: PCR in principle can detect a single target molecule in a reaction
      mixture. Contaminating bacterial DNA in reagents creates a practical limit on the
      use of PCR to detect dilute bacterial DNA in environmental or public health
      samples. The most pernicious source of contamination is microbial DNA in DNA
      polymerase preparations. Importantly, all commercial Taq polymerase preparations
      inevitably contain contaminating microbial DNA. Removal of DNA from an enzyme
      preparation is problematical. METHODOLOGY/PRINCIPAL FINDINGS: This report
      demonstrates that the background of contaminating DNA detected by quantitative
      PCR with broad host range primers can be decreased greater than 10-fold through
      the simple expedient of Taq enzyme dilution, without altering detection of target
      microbes in samples. The general method is: For any thermostable polymerase used
      for high-sensitivity detection, do a dilution series of the polymerase crossed
      with a dilution series of DNA or bacteria that work well with the test primers.
      For further work use the concentration of polymerase that gave the least signal
      in its negative control (H(2)O) while also not changing the threshold cycle for
      dilutions of spiked DNA or bacteria compared to higher concentrations of Taq
      polymerase. CONCLUSIONS/SIGNIFICANCE: It is clear from the studies shown in this
      report that a straightforward procedure of optimizing the Taq polymerase
      concentration achieved "treatment-free" attenuation of interference by
      contaminating bacterial DNA in Taq polymerase preparations. This procedure should
      facilitate detection and quantification with broad host range primers of a small
      number of bona fide bacteria (as few as one) in a sample.

PMID- 19753124
TI  - Long-term efficacy and safety of anastrozole for adjuvant treatment of early
      breast cancer in postmenopausal women.
AB  - For more than 20 years, tamoxifen has been the gold standard for the adjuvant
      treatment of postmenopausal women with hormone-responsive early breast cancer.
      However, recent randomized trials have shown efficacy and tolerability benefits
      with the third-generation aromatase inhibitor anastrozole, resulting in an
      increased use of this agent in the adjuvant setting. Data on anastrozole's long
      term efficacy and tolerability are therefore of interest in clinical practice and
      will be reviewed here, especially in the light of the 100-month analysis of the
      ATAC (Anastrozole, Tamoxifen Alone or in Combination) trial.

PMID- 19753125
TI  - Antimalarials and the fight against malaria in Brazil.
AB  - Malaria, known as the "fevers," has been treated for over three thousand years in
      China with extracts of plants of the genus Artemisia (including Artemisia annua,
      A. opiacea, and A. lancea) from which the active compound is artemisin, a
      sesquiterpene that is highly effective in the treatment of the disease,
      especially against young forms of the parasite. South American Indians in the
      seventeenth century already used an extract of the bark of chinchona tree,
      commonly named "Jesuits' powder." Its active compound was isolated in 1820 and
      its use spread all over the world being used as a prophylactic drug during the
      construction of the Madeira-Mamore railroad in the beginning of the twentieth
      century. During the 1920s to the 1940s, new antimalarial drugs were synthesized
      to increase the arsenal against this parasite. However, the parasite has
      presented systematic resistence to conventional antimalarial drugs, driving
      researchers to find new strategies to treat the disease. In the present review we
      discuss how Brazil treats Plasmodium-infected patients.

PMID- 19753126
TI  - Associations of anemia persistency with medical expenditures in Medicare ESRD
      patients on dialysis.
AB  - Most end-stage renal disease (ESRD) patients begin renal replacement therapy with
      hemoglobin levels below the recommended US National Kidney Foundation Dialysis
      Outcomes Quality Initiative Guidelines lower level of 110 g/L. Although most
      patients eventually reach this target, the time required varies substantially.
      This study aimed to determine whether length of time with below-target hemoglobin
      levels after dialysis initiation is associated with medical costs, and if so,
      whether intermediate factors underlie the associations. US patients initiating
      dialysis in 2002 were studied using the Centers for Medicare and Medicaid
      Services ESRD database. Anemia persistence (time in months with hemoglobin below
      110 g/L) was determined in a six-month entry period, and outcomes were assessed
      in the subsequent six-month follow-up period. The structural equation modeling
      technique was used to evaluate associations between persistent anemia and medical
      costs and to determine intermediate factors for these associations. The study
      included 28,985 patients. Mean per-patient-per-month medical cost was $6267
      (standard deviation $5713) in the six-month follow-up period. Each additional
      month with hemoglobin below 110 g/L was associated with an 8.9% increment in
      medical cost. The increased cost was associated with increased erythropoietin use
      and blood transfusions, and increased rates of hospitalization and vascular
      access procedures in the follow-up period.

PMID- 19753127
TI  - Mycophenolic acid formulations in adult renal transplantation - update on
      efficacy and tolerability.
AB  - The description more than 30 years ago of the role of de novo purine synthesis in
      T and B lymphocytes clonal proliferation opened the possibility for selective
      immunosuppression by targeting specific enzymatic pathways. Mycophenolic acid
      (MPA) blocks the key enzyme inosine monophosphate dehydrogenase and the
      production of guanosine nucleotides required for DNA synthesis. Two MPA
      formulations are currently used in clinical transplantation as part of the
      maintenance immunosuppressive regimen. Mycophenolate mofetil (MMF) was the first
      MPA agent to be approved for the prevention of acute rejection following renal
      transplantation, in combination with cyclosporine and steroids. Enteric-coated
      mycophenolate sodium (EC-MPS) is an alternative MPA formulation available in
      clinical transplantation. In this review, we will discuss the clinical trials
      that have evaluated the efficacy and safety of MPA in adult kidney
      transplantation for the prevention of acute rejection and their use in new
      combination regimens aiming at minimizing calcineurin inhibitor toxicity and
      chronic allograft nephropathy. We will also discuss MPA pharmacokinetics and the
      rationale for therapeutic drug monitoring in optimizing the balance between
      efficacy and safety in individual patients.

PMID- 19753129
TI  - Adipokines in nonalcoholic steatohepatitis: from pathogenesis to implications in
      diagnosis and therapy.
AB  - Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the
      metabolic syndrome and can vary from benign steatosis to end-stage liver disease.
      The pathogenesis of non-alcoholic steatohepatitis (NASH) is currently thought to
      involve a multiple-hit process with the first hit being the accumulation of liver
      fat which is followed by the development of necroinflammation and fibrosis. There
      is mounting evidence that cytokines secreted from adipose tissue, namely,
      adipokines, are implicated in the pathogenesis and progression of NAFLD. In the
      current review, we explore the role of these adipokines, particularly leptin,
      adiponectin, resistin, tumor necrosis factor-a, and interleukin-6 in NASH, as
      elucidated in experimental models and clinical practice. We also comment on their
      potential use as noninvasive markers for differentiating simple fatty liver from
      NASH as well as on their potential future therapeutic role in patients with NASH.

PMID- 19753130
TI  - Extraskeletal osteosarcoma of the thigh: an autopsy case report.
AB  - We report a case of extraskeletal osteosarcoma (ESOS) and autopsy findings. A 35
      year-old man presented with an ossified tumor in the right thigh and lung
      metastasis. The lung tumors continued to develop despite multiagent chemotherapy
      and caused death within 8 months. Autopsy revealed many secondary lesions in the
      lungs, especially in the left lung. Histopathologically, the primary tumor and
      one of the secondary tumors showed proliferation of spindle-shaped tumor cells
      focally forming lace-like osteoid material. Therefore, we made a definite
      diagnosis of ESOS.

PMID- 19753131
TI  - Probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 may help
      downregulate TNF-Alpha, IL-6, IL-8, IL-10 and IL-12 (p70) in the neurogenic
      bladder of spinal cord injured patient with urinary tract infections: a two-case
      study.
AB  - The management of urinary tract infection (UTI) in individuals with spinal cord
      injury (SCI) continues to be of concern, due to complications that can occur. An
      emerging concept that is a common underlying pathophysiological process is
      involved, wherein pathogens causing UTI have a role in inflammatory progression.
      We hypothesized that members of the commensal flora, such as lactobacilli, may
      counter this reaction through anti-inflammatory mediation. This was assessed in a
      pilot two-patient study in which probiotic Lactobacillus rhamnosus GR-1 and
      Lactobacillus reuteri were administered to one patient and placebo to another,
      both along with antibiotics to treat acute UTI. Urinary TNF-alpha was
      significantly downregulated (P = .015) in the patient who received the probiotic
      and who used intermittent catheterization compared with patient on placebo and
      using an indwelling catheter. The extent to which this alteration resulted in
      improved well-being in spinal cord injured patients remains to be determined in a
      larger study.

PMID- 19753133
TI  - Luteal Phase Support in assisted reproductive technology treatment: focus on
      Endometrin(R) (progesterone) vaginal insert.
AB  - Supplementation of progesterone in the luteal phase and continuance of
      progesterone therapy during the first trimester has been found in several studies
      to have benefits in promoting fertility, preventing miscarriages and even
      preventing pre-term labor. Though it can be administered orally, intramuscularly
      or even sublingually, a very effective route with fewer side effects can be
      achieved by an intravaginal route. The first vaginal preparations were not made
      commercially but were compounded by pharmacies. This had the disadvantage of lack
      of control by the Food and Drug Administration (FDA) ensuring efficacy of the
      preparations. Furthermore there was a lack of precise dosing leading to batch to
      batch variation. The first commercially approved vaginal progesterone preparation
      in the United States was a vaginal gel which has proven very effective. The main
      side effect was accumulation of a buildup of the vaginal gel sometimes leading to
      irritation. Natural micronized progesterone for vaginal administration with the
      brand name of Utrogestan A((R)) had been approved even before the gel in certain
      European countries. Endometrin((R)) vaginal tablets are the newest natural
      progesterone approved by the FDA. Comparisons to the vaginal gel and to
      intramuscular progesterone have shown similar efficacy especially in studies
      following controlled ovarian hyperstimulation and oocyte egg retrieval and embryo
      transfer. Larger studies are needed to compare side effects.

PMID- 19753134
TI  - Minimizing cardiac surgery risks in a Hepatitis C patient: Changing surgical
      strategy after evaluation by modern imaging technologies.
AB  - Minimizing operative risks for the surgical team in infectious patients is
      crucial. We report on a patient suffering from Hepatitis C undergoing re
      operative aortic valve and ascending aorta replacement for aortic aneurysm and
      paravalvular leakage due to recurrent endocarditis of a Smeloff-Cutter aortic
      ball prosthesis. Preoperative multi-slice computed tomography and real-time three
      dimensional echocardiography proved helpful in changing operative strategy by
      detecting a previously unknown aortic aneurysm, assessing its extent, and
      demonstrating the close proximity of the right coronary artery, right ventricle,
      and the aortic aneurysm to the sternum. Thus, cardiopulmonary bypass was
      instituted via the femoral vessels, instead of conventionally. Location,
      morphology, and extent of the paravalvular defect could also be assessed.

PMID- 19753135
TI  - Role of rasagiline in treating Parkinson's disease: Effect on disease
      progression.
AB  - Rasagiline is a second generation, selective, irreversible monoamine oxidase type
      B (MAO-B) inhibitor. It has demonstrated efficacy in monotherapy for early
      Parkinson's disease (PD) patients in one large randomized, placebo-controlled
      trial (TVP-1012 in Early Monotherapy for Parkinson's Disease Outpatients), and
      has shown ability to reduce off time in more advanced PD patients with motor
      fluctuations in two large placebo-controlled trials (Parkinson's Rasagiline:
      Efficacy and Safety in the Treatment of "Off", and Lasting Effect in Adjunct
      Therapy With Rasagiline Given Once Daily). Preclinical data abound to suggest
      potential for neuroprotection by this compound against a variety of neurotoxic
      insults in cell cultures and in animals. The lack of amphetamine metabolites
      provides an advantage over the first generation MAO-B inhibitor selegiline. One
      large trial has investigated the potential for disease modification in PD
      patients (Attenuation of Disease progression with Azilect Given Once-daily) and
      preliminary results maintain some possible advantage to earlier initiation of the
      1 mg/day dose. The clinical significance of the difference detected remains a
      consideration.

PMID- 19753136
TI  - Treatment of recurrent epithelial ovarian cancer.
AB  - Epidemiologic analysis reveals that the mortality rate from ovarian cancer is
      continuously decreasing due to the improvement of surgery and chemotherapy.
      However, the prognosis of ovarian cancer patients is still unsatisfactory overall
      considering that only 30% of patients are alive after five years. In fact,
      although surgery and first-line systemic chemotherapy induces complete and
      partial response in up to 80% of patients with about a 25% pathological complete
      remission rate, recurrences occur in the majority of patients. The role of
      surgery in recurrent disease has been recently studied and many patients can
      receive an optimal secondary cytoreduction. Most of the recurrent patients are
      subject to a number of treatment regimens that, although palliative in nature,
      are also able to prolong survival. Important results have been obtained in
      particular in platinum-sensitive recurrent disease where a platinum-based
      chemotherapy is able to prolong progression-free survival and overall survival.
      Overall, our armamentarium for the treatment of progressive or recurrent ovarian
      cancer is significantly richer than in the past, and in many patients it is
      possible to achieve our goal of controlling the chronic behavior of the disease.

PMID- 19753137
TI  - Iatrogenic bile duct injury associated with anomalies of the right hepatic
      sectoral ducts: a misunderstood and underappreciated problem.
AB  - Although laparoscopic cholecystectomy (LC) has been widely accepted as the
      standard of care, it continues to have a higher complication rate than open
      cholecystectomy. Bile duct injury with LC has often been attributed to surgical
      inexperience, but it is also clear that aberrant bile ducts are present in a
      significant number of patients who sustain biliary injuries during these
      procedures. We present three cases of right sectoral hepatic duct injuries which
      occurred during LC and provide a discussion of the conditions which are likely to
      lead to these injuries, as part of a strategy to prevent them.

PMID- 19753138
TI  - Synthesis and evaluation of novel organogermanium sesquioxides as antitumor
      agents.
AB  - Five new organogermanium sesquioxides have been synthesized and characterized by
      elemental analysis and IR spectra. All the compounds were tested for antitumor
      activities against KB, HCT, and Bel cells in vitro. Compound 5 (gamma
      thiocarbamido propyl germanium sesquioxide) showed excellent antitumor activity,
      and its inhibition yield to KB, HCT, and Bel cells was 92.9%, 84.9%, and 70.9%,
      respectively. A rapid method was described for the labeling compound 5 with
      (99m)Tc, and the optimum labeling conditions were investigated. The labeling
      yield is above 90% in pH 7.0, 20 degrees C, reaction time greater than 10
      minutes, 1 mg of compound 5, and 0.075 approximately 0.1 mg of SnCl(2). The
      biodistribution of (99m)Tc labeled compound 5 in nude mice bearing human colonic
      xenografts was studied. The result showed that the tumor uptakes were 0.73, 0.97,
      0.87, and 0.62 ID%/g at 1-hour, 3-hour, 6-hour, and 20-hour postinjection,
      respectively. T/NT (the uptake ratio for per gram of tumor over normal tissues)
      was 18.3 for tumor versus brain and 5.81 for tumor versus muscle at 20-hour
      postinjection. The tumor clearance was slow. The results showed that compound 5
      may be developed to be a suitable cancer therapeutic agent.

PMID- 19753139
TI  - New means of canine leishmaniasis transmission in north america: the possibility
      of transmission to humans still unknown.
AB  - At present it is not possible to determine in advance the outcome of Leishmania
      infantum infection. Canine Visceral Leishmaniasis (VL), caused by Le. infantum,
      is a natural disease process which offers a insight into the interaction of the
      host and resultant disease outcome. Canine VL results in the same altered
      pathophysiology and immunodysregulation seen in humans. VL in US dogs is likely
      to be transmitted primarily via nontraditional, nonvector means. VL mediated by
      Le. infantum is endemic in U.S. Foxhound dogs, with vertical transmission likely
      to be the novel primary means of transmission. This population of dogs offers an
      opportunity to identify host factors of natural disease. Prevention of human
      clinical visceral leishmaniasis can occur only by better understanding the
      disease ecology of the primary reservoir host: the dog.

PMID- 19753140
TI  - Network structure and biological function: reconstruction, modeling, and
      statistical approaches.

PMID- 19753141
TI  - Bioinformatics tools for plant genomics.

PMID- 19753142
TI  - Activation in the VTA and nucleus accumbens increases in anticipation of both
      gains and losses.
AB  - To represent value for learning and decision making, the brain must encode
      information about both the motivational relevance and affective valence of
      anticipated outcomes. The nucleus accumbens (NAcc) and ventral tegmental area
      (VTA) are thought to play key roles in representing these and other aspects of
      valuation. Here, we manipulated the valence (i.e., monetary gain or loss) and
      personal relevance (i.e., self-directed or charity-directed) of anticipated
      outcomes within a variant of the monetary incentive delay task. We scanned young
      adult participants using functional magnetic resonance imaging (fMRI), utilizing
      imaging parameters targeted for the NAcc and VTA. For both self-directed and
      charity-directed trials, activation in the NAcc and VTA increased to anticipated
      gains, as predicted by prior work, but also increased to anticipated losses.
      Moreover, the magnitude of responses in both regions was positively correlated
      for gains and losses, across participants, while an independent reward
      sensitivity covariate predicted the relative difference between and gain- and
      loss-related activation on self-directed trials. These results are inconsistent
      with the interpretation that these regions reflect anticipation of only positive
      valence events. Instead, they indicate that anticipatory activation in reward
      related regions largely reflects the motivational relevance of an upcoming event.

PMID- 19753145
TI  - Teaching-learning: an integral component of sound patient care.

PMID- 19753143
TI  - Mammalian olfactory receptors.
AB  - Perception of chemical stimuli from the environment is essential to most animals;
      accordingly, they are equipped with a complex olfactory system capable of
      receiving a nearly unlimited number of odorous substances and pheromones. This
      enormous task is accomplished by olfactory sensory neurons (OSNs) arranged in
      several chemosensory compartments in the nose. The sensitive and selective
      responsiveness of OSNs to odorous molecules and pheromones is based on distinct
      receptors in their chemosensory membrane; consequently, olfactory receptors play
      a key role for a reliable recognition and an accurate processing of chemosensory
      information. They are therefore considered as key elements for an understanding
      of the principles and mechanisms underlying the sense of smell. The repertoire of
      olfactory receptors in mammals encompasses hundreds of different receptor types
      which are highly diverse and expressed in distinct subcompartments of the nose.
      Accordingly, they are categorized into several receptor families, including
      odorant receptors (ORs), vomeronasal receptors (V1Rs and V2Rs), trace amine
      associated receptors (TAARs), formyl peptide receptors (FPRs), and the membrane
      guanylyl cyclase GC-D. This large and complex receptor repertoire is the basis
      for the enormous chemosensory capacity of the olfactory system.

PMID- 19753144
TI  - Prevalence and significance of coagulation abnormalities in community-acquired
      pneumonia.
AB  - Coagulation abnormalities are common in severe pneumonia and sepsis, yet little
      is known about the presence of coagulopathy or its significance in patients with
      lesser illness severity. We examined coagulation abnormalities in 939 subjects
      hospitalized with community-acquired pneumonia (CAP) in 28 US hospitals,
      hypothesizing that abnormalities would increase with illness severity and poor
      outcomes. We measured plasma coagulation markers (D-dimer, plasminogen activator
      inhibitor [PAI], antithrombin, factor IX, and thrombin-antithrombin complex
      [TAT]) at the time of patient presentation to the emergency department and daily
      during the first wk of hospitalization. Day-1 clinical laboratory test results
      for international normalized ratio, activated partial thromboplastin time, and
      platelet count were recorded from the medical record. In our cohort, 32.5% of
      patients developed severe sepsis and 11.1% died by d 90. Day-1 coagulation
      abnormalities were common, especially for D-dimer (80.6%) and TAT (36.0%), and
      increased with illness severity and poor outcomes. However, abnormalities also
      occurred in those patients who never developed organ dysfunction and differences
      between groups were modest. The proportion of patients with abnormalities changed
      over time, yet the magnitude of change was small and not always in the direction
      of normality. Many patients remaining in the hospital continued to manifest
      coagulation abnormalities on d 7, especially for D-dimer (86.5%) and TAT (36.9%).
      In conclusion, coagulation abnormalities were common and persistent in CAP
      patients, even among the least ill. These findings underscore the complexity of
      the coagulation response to infection and may offer insights into coagulation
      based therapeutics in clinical sepsis trials.

PMID- 19753146
TI  - On the education of the orthopedic resident.

PMID- 19753147
TI  - Orthopedic education: Indian perspective.

PMID- 19753148
TI  - The Cochrane Collaboration: a leading role in producing reliable evidence to
      inform healthcare decisions in musculoskeletal trauma and disorders.
AB  - Systematic reviews are a key component of evidence-based practice. A valuable and
      accessible source of good quality systematic reviews on topics in musculoskeletal
      trauma and disorders is the Cochrane Database of Systematic Reviews, published in
      The Cochrane Library. These reviews are produced by members of The Cochrane
      Collaboration, an international not-for-profit organization that aims to make up
      to-date, accurate information about the effects of healthcare readily available
      worldwide. Contributions from orthopedic specialists in India and neighboring
      countries are required to make the Cochrane Database an even more useful and
      comprehensive resource of reliable evidence. Linked with this is the opportunity
      for orthopedic specialists to take a leading role in generating the evidence to
      inform their practice.

PMID- 19753150
TI  - Anthropometric study of the hip joint in northeastern region population with
      computed tomography scan.
AB  - BACKGROUND: Anthropometric study of the hip joint has important clinical
      implications and is largely unknown for the northeastern region of India. The
      purpose of this study is to determine the anatomic variation of the normal hip
      joint among the people of the northeastern region and to statistically compare
      them with the available data worldwide. MATERIALS AND METHODS: We evaluated 104
      individuals with normal hip joints and of different ethnic backgrounds (Caucasoid
      and Mongoloids) clinically and by plain x- ray. One topogram of the hip joint,
      one axial section of the femoral head and femoral condyles of the individual was
      taken on CT scan. Twelve cases had center edge angle (CE) angle less than 20
      degrees (unilateral/bilateral), were considered to be dysplastic and were
      excluded from the study. Thus the present study includes 92 individuals (184
      normal hips, Mongoloids = 45; Caucasoid = 47) between 20-70 years of age. We
      calculated the mean of the CE angle, acetabular angle, neck shaft angle,
      acetabular version, femoral neck anteversion, acetabular depth and joint space
      width in both sexes. RESULTS: The mean parameters observed were as follows:
      acetabular angle 39.2 degrees, centre edge angle 32.7 degrees, neck shaft angle
      139.5 degrees, acetabular version 18.2 degrees, femoral neck anteversion 20.4
      degrees, acetabular depth 2.5 cm and joint space width 4.5 mm. CONCLUSION: The
      parameter and its values in our series shows differences when compared to the
      other western literatures. The neck shaft angle and the femoral neck anteversion
      in our individuals was 5-6 degrees more than the western literature. The
      remaining parameters were less or equal to the western literature.

PMID- 19753149
TI  - The unstable total hip replacement.
AB  - BACKGROUND: Dislocation is one of the most common complications of total hip
      arthroplasty with a reported dislocation rate of 3.2%. Despite increased
      experience with hip replacement, the overall rate has not yet changed. The aim of
      this paper is to review the most recent literature published on this topic and
      indexed in Medline, in order to clarify the main risk factors, and to standardize
      a treatment protocol of such an important complication of prosthetic surgery.
      MATERIALS AND METHODS: Medline database was searched using key words: "hip
      dislocation", "hip instability" from 1980-2007. Studies were eligible for review
      and included if they met the following criteria: (1) publication in English, (2)
      clinical trials (3) review papers. RESULTS: The risk of first-time dislocation as
      a function of time after the surgery is not well understood. Most, but not all,
      series have demonstrated that the risk of dislocation is highest during the first
      few months after hip arthroplasty; however, first-time late dislocation can also
      occur many years after the procedure. Several risk factors were described,
      including the surgical approach, the diameter of the head, impingement, component
      malposition, insufficient abductor musculature. In addition, there are also many
      treatment options, such as long-term bracing after closed reduction, component
      reorientation, capsulorraphy, trochanteric advancement, increasing offset,
      exchange of the modular head and the polyethylene liner, insertion of constrained
      liner. CONCLUSION: Preventing hip dislocation is obviously the best strategy.
      Surgeons must take into account patient and surgical risk factors. For patients
      at high risk for dislocation the surgeon should accurately restore leg length and
      femoral offset; the use of larger femoral heads, posterior transosseous repair of
      the capsulotendinous envelope if posterior approach is chosen or the use of a
      lateral approach should be considered. Proper patient education and postoperative
      care are very important.

PMID- 19753151
TI  - A modified two-incision technique for primary total hip arthroplasty.
AB  - BACKGROUND: Minimally invasive surgery can be technically demanding but minimizes
      surgical trauma, pain and recovery. Two-incision minimally invasive surgery
      allows only intermittent visualization and may require fluoroscopy for implant
      positioning. We describe a modified technique for primary total hip arthroplasty,
      using two small incisions with a stepwise approach and adequate visualization to
      reliably and reproducibly perform the surgery without fluoroscopy. MATERIALS AND
      METHODS: One hundred and two patients with an average age of 60 years underwent
      modified two-incision minimally invasive technique for primary THA without
      fluoroscopy. The M/L taper femoral stem (Zimmer, Warsaw, IN) and Trilogy (Zimmer)
      hemispherical titanium shell, with a highly cross-linked polyethylene liner, was
      used. Operative time, blood loss, postoperative hospital stay, radiographic
      outcomes and complications were recorded. RESULTS: The mean operating time was 77
      min. The mean blood loss was 335 cc. The mean hospital stay was 2.4 days. Mean
      cup abduction angle was 43.8 degrees. Mean leg length discrepancy was 1.7 mm.
      Thirteen patients had lateral thigh numbness and two patients had wound
      complications that resolved without any treatment. CONCLUSION: A modified two
      incision technique without fluoroscopy for primary total hip arthroplasty has the
      advantage of preserving muscles and tendons, shorter recovery and return to
      function with minimal complications. Provided that the surgeon has received
      appropriate training, primary total hip arthroplasty can be performed safely with
      the modified two-incision technique.

PMID- 19753152
TI  - Analysis of bone ingrowth on a tantalum cup.
AB  - BACKGROUND: Trabecular Metal (TM) is a new highly porous material made of
      tantalum (Zimmer, Warsaw, Indiana, USA). Its three-dimensional structure is
      composed of a series of interconnected dodecahedron pores that are on average 550
      microm in diameter. This size is considered optimal for bone ingrowth and is
      similar to trabecular bone. The elastic modulus of TM (3 GPa) is more similar to
      that of cancellous (0,1-1,5 GPa) or cortical (112-18 GPa) bone and is
      significantly less similar to that of Titanium (110 GPa) and Co-Cr alloys (220
      GPa). These features enable bone apposition and remodeling. The purpose of the
      present study was to evaluate the histology of the bone-implant interface in a
      human specimen. MATERIALS AND METHODS: A highly porous tantalum cup (Zimmer,
      Warsaw, Indiana, USA) was removed for recurrent dislocations three years after
      implantation. In order to obtain a slice of the cup, two cuts were made on the
      centre using an Exakt cutting machine. Then the slice was embedded in a Technovit
      resin and a Hematoxylin-eosin stain was used to study the bone tissue. Bone
      ingrowth was calculated using a method based on simple calculations of planar
      geometry. RESULTS: The histological evaluation of the periprosthetic tissues
      revealed a typical chronic inflammation with few particles of polyethylene that
      were birefringent using polarized light. The quantitative evaluation of bone
      ingrowth revealed that more than 95% of voids were filled with bone. DISCUSSION:
      In the literature, a lot of studies focused on tantalum were carried on animal
      model. Up to now little information is available about the histology of the bone
      tantalum interface in a human artificial joint. We had an opportunity to remove a
      well integrated cup hence this study. The histology confirmed the strong
      relationship between the structure of this material and bone. The morphometric
      analysis revealed a high percentage of bone ingrowth.

PMID- 19753153
TI  - Total hip arthroplasty following failed fixation of proximal hip fractures.
AB  - BACKGROUND: Most proximal femoral fractures are successfully treated with
      internal fixation but a failed surgery can be very distressing for the patient
      due to pain and disability. For the treating surgeon it can be a challenge to
      perform salvage operations. The purpose of this study was to evaluate the short
      term functional outcome and complications of total hip arthroplasty (THA)
      following failed fixation of proximal hip fracture. MATERIALS AND METHODS: In a
      retrospective study, 21 hips in 20 patients (13 females and seven males) with
      complications of operated hip fractures as indicated by either established
      nonunion or fracture collapse with hardware failure were analysed. Mean age of
      the patients was 62 years (range 38 years to 85 years). Nine patients were
      treated for femoral neck fracture, 10 for intertrochanteric (I/T) fracture and
      two for subtrochanteric (S/T) fracture of the hip. Uncemented THA was done in 11
      cases, cemented THA in eight hip joints and hybrid THA in two patients. RESULTS:
      The average duration of follow-up was four years (2-13 years). The mean duration
      of surgery was 125 min and blood loss was 1300 ml. There were three dislocations
      postoperatively. Two were managed conservatively and one was operated. There was
      one superficial infection and one deep infection. Only one patient required a
      walker while four required walking stick for ambulation. The mean Harris Hip
      score increased from 32 preoperatively to 79 postoperatively at one year
      interval. CONCLUSION: Total hip arthroplasty is an effective salvage procedure
      after failed osteosynthesis of hip fractures. Most patients have good pain relief
      and functional improvements inspite of technical difficulties and high
      complication rates than primary arthroplasty.

PMID- 19753154
TI  - Extensively coated revision stems in proximally deficient femur: early results in
      15 patients.
AB  - BACKGROUND: Hip replacement following failed internal fixation (dynamic hip screw
      for intertrochanteric fractures) or previous hip arthroplasty presents a major
      surgical challenge. Proximal fitting revision stems do not achieve adequate
      fixation. Distal fixation with long-stemmed extensively coated cementless
      implants (like the Solution system) affords a suitable solution. We present our
      early results of 15 patients treated with extensively coated cementless revision
      stems. MATERIALS AND METHODS: Fifteen patients with severely compromised proximal
      femora following either failed hip arthroplasty or failed internal fixation
      (dynamic hip screw fixation for intertrochanteric fractures) were operated by the
      senior author over a two-year period. Eight patients had aseptic loosening of
      their femoral stems following cemented hip replacements, with severe thinning of
      their proximal cortices and impending stress fractures. Seven had secondary hip
      arthritis following failure of long implants for comminuted intertrochanteric or
      subtrochanteric femoral fractures. All patients were treated by removal of
      implant (cemented stems/DHS implants) and insertion of long-stemmed extensively
      coated cementless revision ('Solution DePuy, Warsaw (IN), US') stems along with
      press-fit acetabular component (Duraloc Cup, DePuy, Warsaw (IN), US). All eight
      hip revisions needed extended trochanteric osteotomies. RESULTS: All patients
      were primarily kept in bed on physiotherapy for six weeks and then gradually
      progressed to weight-bearing walking over the next six to eight weeks. The Harris
      Hip Scores and patient satisfaction were used for final evaluation. We achieved
      good results in the short term studied. In our first three patients (all
      following failed cemented total hip replacements), we resorted to cerclage wiring
      to hold osteotomised segments (done to facilitate stem removal). The subsequent
      12 proceeded without the need for cerclage wiring. One patient had a
      intraoperative severe comminuted fracture extending into the supracondylar region
      while hammering in the stem. Post cerclage wiring, she was put on a long knee
      brace and her mobilization was delayed to 12 weeks. CONCLUSIONS: The extensively
      coated cementless ('Solution') femoral stem provides a reasonable 'solution' to
      the deficient femur in hip revision. The proximal femoral deficiences can be
      relatively easily bypassed and distal fixation can be achieved with this stem.
      Extreme care needs to be taken to avoid fractures and penetration of the femoral
      shaft, which can, however, be managed by cerclage wiring. Principles of a
      successful outcome include preservation of the functional continuity of the
      abduction apparatus, care to recognize and prevent distal extension of fracture
      while inserting the stem (preemptive cerclage wiring) and supervised
      rehabilitation.

PMID- 19753155
TI  - Conversion of failed hemiarthroplasty to total hip arthroplasty: a short to mid
      term follow-up study.
AB  - BACKGROUND: The conversion of hemiarthroplasty (unipolar or bipolar) of the hip
      to total hip replacement has been reported to be associated with very high rates
      of intra- and postoperative complications. We present a prospective analysis of
      the outcome of conversion surgery in patients with failed hemiarthroplasty.
      MATERIALS AND METHODS: Forty-four cases, 30 women and 14 men, average age 62
      years (range 42-75 years) of failed hemiarthroplasty were converted to total hip
      replacement between January 1998 and December 2004. Groin pain was the main
      presenting complaint in the majority of the patients (24 out of 44). Six patients
      had infection and were operated with staged procedure. All acetabular and the
      majority (86.5%) of femoral components used in our series were uncemented.
      RESULTS: After an average follow-up of 6.4 years (range, two to nine years)
      Harris hip scores improved from 38 (range 15-62) preoperatively to 86 (range 38
      to 100) and 22 (50%) patients were community ambulators without support while 17
      (38%) needed minimal support of cane. Fifteen out of 18 (83%) patients who had
      isolated groin pain preoperatively experienced no pain postoperatively while
      three patients (17%) reported only partial improvement. Intraoperative and
      postoperative complications included iatrogenic fracture of the femur in two,
      femoral perforation in two, partial trochanteric avulsion in two, fracture of the
      acetabular floor in three hips, and postoperative dislocation in one. None of
      these complications resulted in a poor long-term outcome. The rate of loosening
      in our series was 2.3% (one out of 44) after a mean follow-up of 6.4 years with a
      mean survival of 97.4% at 72 months. CONCLUSION: Conversion of symptomatic
      hemiarthroplasty to total hip arthroplasty is a safe option that gives good
      functional results, with marginally higher rates of intra-operative
      complications. The patients should be warned of the possibility of incomplete
      relief of groin pain postoperatively.

PMID- 19753156
TI  - Minimally invasive total hip arthroplasty with the anterior approach.
AB  - BACKGROUND: Total hip athroplasty with the anterior surgical approach is advised
      because the dissection is entirely within intermuscular planes. In this report we
      describe a minimally invasive technique of anterior total hip arthroplasty, with
      the early outcomes. MATERIALS AND METHODS: The technique of minimally invasive
      total hip arthroplasty with anterior approach (Smith-Petersen) is described. We
      reviewed data on 100 consecutive patients who underwent anterior total hip
      arthroplasty with uncemented components. Mean patient age was 61 years (range 33
      91). Mean patience BMI 29.8 (range 18.1-51.8). RESULTS: Minimum follow up
      duration is 10 months. The mean duration of surgery was 53 min (range 34-87) with
      mean blood loss 185 cc (range 65-630), and the mean incision length was 10.4 cm.
      Clinical and radiographic outcomes were similar to historical outcomes of
      standard total hip arthroplasty. CONCLUSIONS: With proper surgeon training,
      minimally invasive total hip replacement with the anterior surgical interval is
      safe and efficacious.

PMID- 19753157
TI  - Tibial torsion in non-arthritic Indian adults: a computer tomography study of 100
      limbs.
AB  - BACKGROUND: Knowledge of normal tibial torsion is mandatory during total knee
      replacement (TKR), deformity correction and fracture management of tibia.
      Different values of tibial torsion have been found in different races due to
      biological and mechanical factors. Value of normal tibial torsion in Indian limbs
      is not known, hence this study to determine the norm of tibial torsional value in
      normal Indian population. MATERIALS AND METHODS: Computer tomography (CT) scans
      were performed in 100 non-arthritic limbs of 50 Indian adults (42 males, eight
      females; age 26-40 years). Value of tibial torsion was measured using dorsal
      tangent to tibial condyles proximally and bimalleolar axis distally. RESULTS:
      Normal tibial torsion was found to be 21.6 +/- 7.6 (range 4.8 to 39.5) with none
      of the values in internal rotation. Right tibia was externally rotated by 2
      degrees as compared to the left side (P 0.029). No significant difference was
      found in male and female subjects. Value of tibial torsion was less than in
      Caucasian limbs, but was comparable to Japanese limbs when studies using similar
      measurement technique were compared. CONCLUSIONS: Indian limbs have less tibial
      torsion than Caucasian limbs but the value of tibial torsion is comparable to
      Japanese limbs.

PMID- 19753159
TI  - Preliminary experience with biodegradable implants for fracture fixation.
AB  - BACKGROUND: Biodegradable implants were designed to overcome the disadvantages of
      metal-based internal fixation devices. Although they have been in use for four
      decades internationally, many surgeons in India continue to be skeptical about
      the mechanical strength of biodegradable implants, hence this study. MATERIALS
      AND METHODS: A prospective study was done to assess the feasibility and surgeon
      confidence level with biodegradable implants over a 12-month period in an Indian
      hospital. Fifteen fractures (intra-articular, metaphyseal or small bone
      fractures) were fixed with biodegradable implants. The surgeries were randomly
      scheduled so that different surgeons with different levels of experience could
      use the implants for fixation. RESULTS: Three fractures (one humeral condyle, two
      capitulum), were supplemented by additional K-wires fixation. Trans-articular
      fixator was applied in two distal radius and two pilon fractures where bio-pins
      alone were used. All fractures united, but in two cases the fracture displaced
      partially during the healing phase; one fibula due to early walking, and one
      radius was deemed unstable even after bio-pin and external fixator. CONCLUSIONS:
      Biodegradable -implants are excellent for carefully selected cases of intra
      articular fractures and some small bone fractures. However, limitations for use
      in long bone fractures persist and no great advantage is gained if a "hybrid"
      composite is employed. The mechanical properties of biopins and screws in
      isolation are perceived to be inferior to those of conventional metal implants,
      leading to low confidence levels regarding the stability of reduced fractures;
      these implants should be used predominantly in fracture patterns in which
      internal fixation is subjected to minimal stress.

PMID- 19753158
TI  - The results of knee manipulation for stiffness after total knee arthroplasty with
      or without an intra-articular steroid injection.
AB  - BACKGROUND: Stiffness after total knee arthroplasty (TKA) requiring manipulation
      has a reported incidence of 1.3-54%. The purpose of this study was to compare the
      incidence of stiffness warranting manipulation using two different pain
      management protocols. We also studied the effect of an intra-articular injection
      of local anesthetic and steroid given at the time of manipulation on the range-of
      motion (ROM) at last follow-up. MATERIALS AND METHODS: A total of 286 TKAs (248
      patients between January 2002 and December 2003) were compared to a second group
      of 292 TKAs (251 patients between January 2004 and March 2006). The first group
      received patient-controlled analgesia (PCA) for postoperative pain management.
      The second group had a peri-articular injection of a steroid-containing local
      anesthetic at the time of surgery, but no postoperative PCA. All patients
      undergoing manipulation in the second group also received a similar intra
      articular injection at the time of manipulation as well. Only patients with
      minimum 12 months follow-up after manipulation were included in the study.
      RESULTS: The overall incidence of stiffness requiring manipulation in both groups
      was similar at 2.4% and 2.1%, respectively (P = 0.1). The end results of
      manipulation with and without injection showed a significantly higher final ROM
      in patients who had had an injection at the time of manipulation (P = 0.001). The
      difference was due to the fact that patients who had an injection lost no motion
      from that achieved at the time of manipulation. CONCLUSION: We were unable to
      demonstrate a significant reduction in the incidence of stiffness after TKA using
      a modern pain management protocol. However, injection of a local anesthetic and
      steroid at the time of manipulation did have a significant influence on
      preserving the ROM that was obtained at the time of manipulation.

PMID- 19753160
TI  - Limb lengthening over a nail can safely reduce the duration of external fixation.
AB  - BACKGROUND: Limb lengthening using Ilizarov external fixation is safe, but the
      consolidation phase tends to take too long. A method that can safely reduce the
      time spent in external fixation would help increase patient tolerance and
      comfort. We report our results of lengthening over nails (LON) method in which an
      interlocking nail was used along with an Ilizarov external fixator to reduce
      external fixation duration in limb lengthening. This is a retrospective study.
      MATERIALS AND METHODS: Twenty-seven lengthening surgeries were done with the LON
      method in 23 patients with 22 tibiae and five femora during the last 12 years.
      Length gain ranged from 1.5 cm to a maximum of 9.8 cm with a mean of 4.6 cm. The
      mean modified Paley difficulty score was 7.6 points. Fourteen associated
      procedures were performed in these patients, including equinus contracture
      releases, supracondylar osteotomies, ilizarov hip reconstruction and ankle
      fusion. We had a 29% rate of complications which included one problem, three
      obstacles and four complications with no serious deep intramedullary infections.
      Our rate of complications compares favorably with series reported in the
      literature. External fixation duration was reduced significantly to a mean of
      17.8 days per cm. CONCLUSIONS: A combination of intramedullary nailing along with
      external fixation significantly reduces external fixation time while maintaining
      low rate of complications. Great care needs to be taken to prevent pin track
      infection and deep intramedullary sepsis.

PMID- 19753161
TI  - Ligamentotaxis for complex calcaneal fractures using Joshi's external
      stabilization system.
AB  - BACKGROUND: Controversies exist in the literature regarding the management of
      complex fractures of the calcaneum. We evaluated a series of complex fractures of
      the calcaneum managed by ligamentotaxis using Joshi's external stabilization
      system (JESS) for its efficacy. MATERIALS AND METHODS: Forty-five patients having
      complex (comminuted, intra-articular fracture with compromised soft tissue
      condition) fractures of the calcaneum, who were treated by external fixator
      (JESS) based on the principle of ligamentotaxis. The gradual distraction was done
      to bring the articular margins together to maintain both alpha and beta angles to
      near normal range. Thirteen (28.9%) patients underwent additional
      corticocancellous bone grafting with elevation of posterior facet. All patients
      were evaluated for their functional outcomes by American Orthopedic Foot and
      Ankle society (AOFAS) Score for the ankle and hind foot. Mean duration of follow
      up was 20.5 months. RESULTS: Forty-two (93.4%) of our patients did well with the
      ligamentotaxis. On evaluating final outcomes by AOFAS, approximately 71% of cases
      showed good results. Eleven patients (24.4%) complained of persistent heel pain
      in the long-term follow-up. Out of these, eight (17.8%) patients were those who
      had severe comminution with almost total loss of calcaneal height. The origin of
      heel pain was not the subtalar joint in all of these patients. On long-term
      follow-up none of these patients suffered from such severe pain so as to compel
      them to change the nature of their activity. CONCLUSION: We conclude that
      ligamentotaxis by JESS provides a viable and user-friendly alternative method of
      management of these complex calcaneal fractures.

PMID- 19753162
TI  - Outcome of early active mobilization after extensor tendon repair.
AB  - BACKGROUND: Traditionally the repaired extensor tendons have been treated
      postoperatively in static splints for several weeks, leading to formation of
      adhesions and prolonged rehabilitation. Early mobilization using dynamic splints
      is common, but associated with many shortcomings. We attempted to study the
      results of early active mobilization, using a simple static splint, and easy-to
      follow rehabilitation plan. MATERIALS AND METHODS: In a prospective study 26
      cases of cut extensor tendons in Zone V to VIII were treated with primary or
      delayed primary repair. Following this, early active mobilization was undertaken,
      using an easy-to-follow rehabilitation plan. The results were assessed according
      to the criteria of Dargan at six weeks and one year. RESULTS: All the 26 patients
      were followed up for one year. 20 out of 26 patients were below 30 years of age,
      involving the dominant hand more commonly (16 patients, 62%). Agriculture
      instruments were the most common mode of injury (13 patients, 50%). The common
      site for injury was extensor zone VI (42%, n = 11). CONCLUSION: Rehabilitation
      done for repaired extensor tendon injuries by active mobilization plan using a
      simple static splint has shown good results.

PMID- 19753163
TI  - Multiple intramedullary nailing of proximal phalangeal fractures of hand.
AB  - BACKGROUND: Proximal phalangeal fractures are commonly encountered fractures in
      the hand. Majority of them are stable and can be treated by non-operative means.
      However, unstable fractures i.e. those with shortening, displacement, angulation,
      rotational deformity or segmental fractures need surgical intervention. This
      prospective study was undertaken to evaluate the functional outcome after
      surgical stabilization of these fractures with joint-sparing multiple
      intramedullary nailing technique. MATERIALS AND METHODS: Thirty-five patients
      with 35 isolated unstable proximal phalangeal shaft fractures of hand were
      managed by surgical stabilization with multiple intramedullary nailing technique.
      Fractures of the thumb were excluded. All the patients were followed up for a
      minimum of six months. They were assessed radiologically and clinically. The
      clinical evaluation was based on two criteria. 1. total active range of motion
      for digital functional assessment as suggested by the American Society for
      Surgery of Hand and 2. grip strength. RESULTS: All the patients showed
      radiological union at six weeks. The overall results were excellent in all the
      patients. Adventitious bursitis was observed at the point of insertion of nails
      in one patient. CONCLUSION: Joint-sparing multiple intramedullary nailing of
      unstable proximal phalangeal fractures of hand provides satisfactory results with
      good functional outcome and fewer complications.

PMID- 19753164
TI  - Congenital vertical talus: treatment by reverse ponseti technique.
AB  - BACKGROUND: The surgery for idiopathic congenital vertical talus (CVT) can lead
      to stiffness, wound complications and under or over correction. There are
      sporadic literature on costing with mixed results. We describe our early
      experience of reverse ponseti technique. MATERIALS AND METHODS: Four cases (four
      feet) of idiopathic congenital vertical talus (CVT) which presented one month
      after birth were treated by serial manipulation and casting, tendoachilles
      tenotomy and percutaneous pinning of talonavicular joint. An average of 5.2
      (range - four to six) plaster cast applications were required to correct the
      forefoot deformity. Once the talus and navicular were aligned based on the
      radiographic talus-first metatarsal axis, percutaneous fixation of the talo
      navicular joint with a Kirschner wire, and percutaneous tendoachilles tenotomy
      under anesthesia was performed following which a cast was applied with the foot
      in slight dorsiflexion. RESULTS: The mean follow-up period for the four cases was
      8.5 months (6-12 months). At the end of the treatment all feet were supple and
      plantigrade but still using ankle foot orthosis (AFO). The mean talocalcaneal
      angle was 70 degrees before treatment and this reduced to 31 degrees after
      casting. The mean talar axis first metatarsal base angle (TAMBA) angle was 60
      degrees before casting and this improved to 10.5 degrees. CONCLUSION: Although
      our follow-up period is small, we would recommend early casting for idiopathic
      CVT along the same lines as the Ponseti technique for clubfoot except that the
      forces applied are in reverse direction. This early casting method can prevent
      extensive surgery in the future, however, a close vigil is required to detect any
      early relapse.

PMID- 19753165
TI  - Infantile tibia vara: treatment of Langenskiold stage IV.
AB  - An eight year old girl presented with a progressively increasing deformity of the
      left proximal tibia since last 2 years. She had no history of trauma, fever and
      swelling of left knee. There were no obvious signs of rickets/muscular dystrophy.
      She had 25 degrees of tibia vara clinically with lateral thrust and a prominent
      fibular head. The radiograph of left knee revealed tibia vara with medial beaking
      and a significant depression of the medial tibial epiphysis and metaphysis. A
      computed tomography (CT) scan revealed significant depression of the medial
      tibial epiphysis but no bony bar in the physis or fusion of the medical tibial
      epiphysis. There was a posterior slope in addition to the medial one. She was
      treated with elevation of the medial tibial hemiplateau with subtuberosity valgus
      derotation dome osteotomy. She also underwent a lateral proximal tibial
      hemiphysiodesis (temporary stapling). A prophylactic subcutaneons anterolateral
      compartment fasciotomy was also performed. All osteotomies united in 2 months.
      All deformities were corrected and she regained a knee range of 0 to 130 degrees.
      At final followup (4 years), there was no recurrence of varus deformity, knee was
      stable, with 1cm of leg length discrepancy. In Langenskiold stage IV tibia vara,
      elevation of medial tibial plateau, a subtuberosity valgus derotation osteotomy
      and a concomitant lateral hemiephiphysiodesis has given good results.

PMID- 19753166
TI  - Posterolateral rotatory instability of elbow: an uncommon entity.
AB  - Posterolateral rotatory instability of elbow is an exceedingly uncommon entity,
      which results from injury to the lateral ligamentous complex. Failure of adequate
      healing of lateral collateral ligaments may necessitate its surgical repair or
      reconstruction. We describe here a boy 12 years of age who was initially treated
      as soft tissue injury and later presented with instability of the same elbow. He
      later required repair of lateral ulnar collateral ligament.

PMID- 19753167
TI  - Spontaneous cervical epidural hematoma: report of a case managed conservatively.
AB  - Spontaneous spinal epidural hematoma is a rare cause of acute spinal cord
      compression. A 25-year-old male presented with a history of sudden onset of
      complete quadriplegia with sensory loss below the neck along with loss of bowel
      and bladder control. He had no history of any constitutional symptoms. He
      reported 10 days later. He was managed conservatively and after two weeks of
      intensive rehabilitation he had complete neural recovery. The spontaneous
      recovery of neurological impairment is attributed to the spreading of the
      hematoma throughout the epidural space, thus decreasing the pressure with partial
      neural recovery. Conservative treatment is a fair option in young patients who
      present late and show neurological improvement. The neurological status on
      presentation will guide the further approach to management.

PMID- 19753168
TI  - Closed posterior dislocation of the ankle without fracture.
AB  - Closed posterior dislocation of the ankle without a fracture is a rare injury. We
      are reporting a case in a young male on his motorbike, being hit at the right
      ankle from behind. The mechanisms of injury along with MRI findings are being
      discussed.

PMID- 19753170
TI  - Long-term results of transpedicle body augmenter in treating burst fractures.

PMID- 19753171
TI  - Avascular necrosis of head of femur.

PMID- 19753172
TI  - Peer review: Heart and soul of scientific publication.

PMID- 19753173
TI  - Management of avascular necrosis of femoral head at pre-collapse stage.
AB  - In osteonecrosis the success of interventions that forestall or prevent femoral
      head collapse and maintain hip function would represent a substantial achievement
      in the treatment of this disease. A review of recent literature regarding
      bisphosphonate, anticoagulant, and vasodilators and biophysical modalities have
      demonstrated efficacy in reducing pain and delaying disease progression in early
      stage osteonecrosis. Though it has been considered still insufficient, to support
      their routine use in the treatment or prevention of osteonecrosis of the hip.
      Core decompression with modification of technique is still one of the safest and
      most commonly employed procedures with evidence based success in the pre-collapse
      stage of AVN of femoral head. The additional use of bone morphogenic protein, and
      bone marrow stem cells may provide the opportunity to enhance the results of core
      decompression. At present, the use of large vascularised cortical grafts, the
      other surgical procedure with high success rate is still not common due to
      technical difficulty in surgery. Likewise osteotomies are also not getting common
      as arthroplasty is getting more acceptable, so is awaited without any
      intermediate big surgical interventions.

PMID- 19753174
TI  - Biophysical stimulation in osteonecrosis of the femoral head.
AB  - Osteonecrosis of the femoral head is the endpoint of a disease process that
      results from insufficient blood flow and bone-tissue necrosis, leading to joint
      instability, collapse of the femoral head, arthritis of the joint, and total hip
      replacement. Pain is the most frequent clinical symptom. Both bone tissue and
      cartilage suffer when osteonecrosis of the femoral head develops. Stimulation
      with pulsed electromagnetic fields (PEMFs) has been shown to be useful for
      enhancing bone repair and for exerting a chondroprotective effect on articular
      cartilage. Two Italian studies on the treatment of avascular necrosis of the
      femoral head with PEMFs were presented in this review. In the first study, 68
      patients suffering from avascular necrosis of the femoral head were treated with
      PEMFs in combination with core decompression and autologous bone grafts. The
      second one is a retrospective analysis of the results of treatment with PEMFs of
      76 hips in 66 patients with osteonecrosis of the femoral head. In both studies
      clinical information and diagnostic imaging were collected at the beginning of
      the treatment and at the time of follow up. Statistical analysis was performed
      using chi-square test. Both authors hypothesize that the short-term effect of
      PEMF stimulation may be to protect the articular cartilage from the catabolic
      effect of inflammation and subchondral bone-marrow edema. The long-term effect of
      PEMF stimulation may be to promote osteogenic activity at the necrotic area and
      prevent trabecular fracture and subchondral bone collapse. PEMF stimulation
      represents an important therapeutic opportunity to resolve the Ficat stage-I or
      II disease or at least to delay the time until joint replacement becomes
      necessary.

PMID- 19753175
TI  - Alendronate preserves femoral head shape and height/length ratios in an
      experimental rat model: A computer-assisted analysis.
AB  - BACKGROUND: Surgical osteonecrosis of the rat femoral head was induced by
      detaching the ligamentum teres and stripping the femoral neck periosteum. Bone
      and marrow necrosis were found from the fifth postoperative day and replaced by
      creeping substitution. Osteonecrosis of the femoral head results in the
      flattening to various degrees of roundness and osteoarthritic changes of the hip
      joint. Alendronate, an osteoclast inhibitor, slows down bone resorption and
      remodeling. The purpose of this study was to evaluate objectively the influence
      of alendronate treatment on the rat femoral head shape after six weeks of daily
      treatment, when compared with controls. MATERIALS AND METHODS: The blood
      circulation of right femoral head of 20 female Sprague-Dawley rats was
      interrupted. Twelve were treated by alendronate injections of 200 microg/kg/day
      and eight controls were treated with saline, both for a total of 42 days. Both
      femoral head specimens were obtained for computed-assisted morphometry. For each
      rat, the right operated head was compared with the left, and the alendronate
      treated group was compared with the control group. RESULTS: No differences were
      found in shape factor and femoral head height/length ratios in the alendronate
      treated femoral heads. Among the nontreated control group, shape-factor
      differences were found between the operated and the nonoperated femoral heads.
      CONCLUSION: Alendronate treatment prevented the distortion and destruction of the
      femoral head. Osteoclast inhibition might prolong the bone creeping substitution
      process and could enable secondary bone maturity and mineralization that
      increases bone strength. Alendronate preserved the femoral head architecture,
      which might reduce morbidity and disability due to femoral head collapse.

PMID- 19753176
TI  - Osteonecrosis of femoral head: Treatment by core decompression and vascular
      pedicle grafting.
AB  - BACKGROUND: Femoral head-preserving core decompression and bone grafting have
      shown excellent result in preventing collapse. The use of vascularized grafts
      have shown better clinical results. The vascular pedicle bone graft is an easy to
      perform operation and does not require special equipment. We analyzed and report
      a series of patients of osteonecrosis of femoral head treated by core
      decompression and vascular pedicle grafting of part of iliac crest based on deep
      circumflex iliac vessels. MATERIALS AND METHODS: The article comprises of the
      retrospective study of 31 patients of osteonecrosis of femoral head in stage II
      and III treated with core decompression and vascular pedicle grafting by using
      part of iliac crest with deep circumflex iliac vessels from January 1990 to
      December 2005. The young patients with a mean age 32 years (18-52 years) with a
      minimum follow-up of five years were included for analysis. Sixteen patients had
      osteonecrosis following alcohol abuse, 12 patients following corticosteroid
      consumption, 3 patients had idiopathic osteonecrosis. Nine patients were stage
      IIB, and 22 patients were stage IIIC according to ARCO's system. The core
      decompression and vascular pedicle grafting was performed by anterior approach by
      using part of iliac crest with deep circumflex iliac vessels. RESULTS: Digital
      subtraction arteriography performed in 9 patients at the end of 12 weeks showed
      the patency of deep circumflex artery in all cases, and bone scan performed in 6
      other patients showed high uptake in the grafted area of the femoral head proving
      the efficacy of the operative procedure. Out of 31 patients, only one patient
      progressed to collapse and total joint replacement was advised. At the final
      follow up period of 5-8 years, Harris Hip Score improved mean +/- SD of 28.2 +/-
      6.4 (p < 0.05). Forty-eight percent of patients had an improvement in Harris Hip
      Score of more that 28 points. CONCLUSION: The core decompression and vascular
      pedicle grafting reduces the intraosseous tension to achieve early
      revascularization of ischemic femoral head. The high percentage of marrow and
      osteogenic cells survive within a vascularized pedicle graft, which helps in
      early vascularization and we have been able to achieve good outcome.

PMID- 19753177
TI  - Outcome of painful bone marrow edema of the femoral head following treatment with
      parenteral iloprost.
AB  - BACKGROUND: Bone marrow edema (BME) is a common cause of hip pain. The aim of the
      study was to assess the efficacy of the vasoactive drug iloprost in the treatment
      of BME of femoral head. MATERIALS AND METHODS: We reviewed 27 patients (19 male,
      8 female) with BME of the femoral head. Their mean age was 53.7 +/- 10.8 years.
      All patients were treated with iloprost, a vasoactive drug that dilates
      arterioles and venules, reduces capillary permeability and suppresses platelet
      aggregation. The therapy comprised a series of five infusions with 20 to 50 mug
      iloprost over 6 h on 5 consecutive days each. Weight bearing was reduced for up
      to 3 weeks, depending on the severity of symptoms. Pain at rest as well as under
      stress was assessed with a semi quantitative scale from before and 4 months after
      therapy. MRI investigations were done before and repeated 4 months after therapy.
      RESULTS: At the clinical follow up of four months after therapy, the pain level
      at rest had diminished by a mean of 58.3% (P < 0.0001). Pain under stress
      decreased by a mean of 41.9% (P < 0.0001). On MRI, 20 patients had a significant
      reduction of BME size or complete normalization and 4 showed no change. Worsening
      of the MRI pattern was found in 3 patients. CONCLUSION: The authors conclude that
      the use of parenteral iloprost might be a viable method in the treatment of BME
      of femoral head.

PMID- 19753178
TI  - Cell therapy of hip osteonecrosis with autologous bone marrow grafting.
AB  - BACKGROUND: One of the reasons for bone remodeling leading to an insufficient
      creeping substitution after osteonecrosis in the femoral head may be the small
      number of progenitor cells in the proximal femur and the trochanteric region.
      Because of this lack of progenitor cells, treatment modalities should stimulate
      and guide bone remodeling to sufficient creeping substitution to preserve the
      integrity of the femoral head. Core decompression with bone graft is used
      frequently in the treatment of osteonecrosis of the femoral head. In the current
      series, grafting was done with autologous bone marrow obtained from the iliac
      crest of patients operated on for early stages of osteonecrosis of the hip before
      collapse with the hypothesis that before stage of subchondral collapse,
      increasing the number of progenitor cells in the proximal femur will stimulate
      bone remodeling and creeping substitution and thereby improve functional outcome.
      MATERIALS AND METHODS: Between 1990 and 2000, 342 patients (534 hips) with
      avascular osteonecrosis at early stages (Stages I and II) were treated with core
      decompression and autologous bone marrow grafting obtained from the iliac crest
      of patients operated on for osteonecrosis of the hip. The percentage of hips
      affected by osteonecrosis in this series of 534 hips was 19% in patients taking
      corticosteroids, 28% in patients with excessive alcohol intake, and 31% in
      patients with sickle cell disease. The mean age of the patients at the time of
      decompression and autologous bone marrow grafting was 39 years (range: 16-61
      years). The aspirated marrow was reduced in volume by concentration and injected
      into the femoral head after core decompression with a small trocar. To measure
      the number of progenitor cells transplanted, the fibroblast colony forming unit
      was used as an indicator of the stroma cell activity. RESULTS: Patients were
      followed up from 8 to 18 years. The outcome was determined by the changes in the
      Harris hip score, progression in radiographic stages, change in volume determined
      by digitizing area of the necrosis on the different cuts obtained on MRI, and by
      the need for hip replacement. Total hip replacement was necessary in 94 hips
      (evolution to collapse) among the 534 hips operated before collapse (Stages I and
      II). Sixty-nine hips with stage I osteonecrosis of the femoral head at the time
      of surgery demonstrated total resolution of osteonecrosis based on preoperative
      and postoperative MRI studies; these hips did not show any changes on plain
      radiographs. Before treatment, these 69 osteonecrosis had only a marginal band
      like pattern as abnormal signal and a volume less than 20 cubic centimeters. The
      intralesional area had kept a normal signal as regards the signal of the femoral
      head outside the osteonecrosis area. For the 371 other hips without collapse at
      the most recent follow up (average 12 years), the mean preoperative volume of the
      osteonecrosis was 26 cm(3) (minimum 12, maximum 30 cm(3)). The mean volume of the
      abnormal signal measured on MRI at the most recent follow up (mean 12 years) was
      12 cm(3). The abnormal signal persisting as a sequelae was seen on T1 images as
      an intralesional area of low intensity signal with a disappearance of the
      marginal band like pattern. CONCLUSION: According to our experience, best
      indication for the procedure is symptomatic hips with osteonecrosis without
      collapse. In some patients who had Steinberg stage III osteonecrosis (subchondral
      lucency, no collapse) successful outcomes (no further surgery) has been obtained
      between 5 to 10 years. Therefore in selected patients, even more advanced disease
      can be considered for core decompression. Patients who had the greater number of
      progenitor cells transplanted in their hips had better outcomes.

PMID- 19753179
TI  - Intrathecal baclofen: Its effect on symptoms and activities of daily living in
      severe spasticity due to spinal cord injuries: A pilot study.
AB  - BACKGROUND: Spasticity is a major problem related to spinal cord injuries. Use of
      intrathecal baclofen with an implanted pump seems a very useful mode of therapy
      in patients in whom oral antispasmodic agents are either not effective or produce
      intolerable side-effects. MATERIALS AND METHODS: Twenty-four patients with mean
      age 50 years (range 32-72 years) had intrathecal baclofen pump implanted for the
      severe spasticity of spinal origin. One patient died following implantation of
      pump due to natural causes and was not included in the study. The patients were
      followed up for mean 22 months (range, one to five years). RESULTS: All 24
      patients showed improvement in their spasm following the procedure. Improvement
      was noted in pain (12), sleep disturbance (20) and sphincter control (14).
      Patients had improvement in activities of daily living such as feeding ability
      (10), self care (10), indoor and outdoor mobility (19), and driving (4). One
      patient had catheter leakage immediately after the surgery and required change of
      catheter. The radio telemetry allows very good adjustment of the dose according
      the individual patients needs. CONCLUSION: Intrathecal baclofen pump improves the
      symptoms of spasm and also the quality of life. It helps the patient to live more
      independently. It is not an irreversible surgery for the patient and hence it is
      very useful in the changing the dynamics in this group of patients.

PMID- 19753180
TI  - Management of open olecranon fractures using clamp-cum-compressor device.
AB  - BACKGROUND: Open fractures of olecranon are not a rare occurrence in patients
      with road traffic accidents particularly motor bike riders who don't use elbow
      guards. Definitive treatment has to be delayed in many till the wound heals. The
      present study was conducted to evaluate the results of open fractures of
      olecranon using clamp-cum-compressor device. MATERIALS AND METHODS: Seventeen
      patients between the ages of 20 and 45 years of open olecranon fractures reported
      5-20 days after injury were treated using an indigenous clamp-cum-compressor. All
      fractures were Mayo type II-A, i.e., displaced, stable and noncomminuted. Four
      patients had Gustilo-Anderson grade I and 13 had Gustilo-Anderson grade II open
      fractures. The patients with transverse or short oblique fractures were included
      in the study. The apparatus was applied under regional anesthesia after thorough
      washing and debridement of wounds with few loose sutures applied wherever needed.
      The wounds healed within 2-4 weeks and fractures united within 8-10 weeks. The
      elbow was mobilized with apparatus still in place. The results were evaluated by
      MayoElbow performance score. RESULTS: We achieved excellent results in twelve
      patients, good in four and poor in one patient, who reported late, hooks of the
      apparatus were cut through the proximal fragment, leading to union of fracture in
      elongation and restricted elbow movements. CONCLUSION: The apparatus was found to
      be quite useful in transverse and short oblique fractures with contamination or
      infection, where internal fixation has to be delayed or avoided.

PMID- 19753181
TI  - Ulnocarpal stabilization in the management of comminuted fractures distal end
      radius.
AB  - BACKGROUND: Malunion due to progressive radial collapse during healing is a
      common complication following comminuted fracture distal radius treated by
      conventional methods. Many treatment modalities have been described with their
      own merits and demerits. Stabilization of ulnocarpal articulation is an effective
      method to prevent radial collapse during healing, and hence this study. MATERIALS
      AND METHODS: A prospective study of 200 patients of comminuted intraarticular
      fracture lower end radius between 20-75 years of age irrespective of sex, treated
      by closed reduction and percutaneous stabilization of ulnocarpal articulation and
      a well-molded above elbow POP cast for 6 weeks has been presented. Patients were
      evaluated at 1 year follow-up and functionally by Sarmiento's modification of
      Lindstrom criteria and Gartland and Werley's criteria. RESULTS: Excellent to good
      results were seen in 92%, fair in 6% and poor in 2% of the cases. Complications
      observed were, pintract infection (n = 6), malunion (n = 6), subluxation of the
      inferior radioulnar joint (n = 4) Sudeck's osteodystrophy (n = 3) and post
      traumatic arthritis of the wrist (n = 3). CONCLUSION: Percutaneous fixation by
      this technique is an effective method to maintain the reduction, prevent radial
      collapse during healing, and to maintain the stability of the distal radioulnar
      joint even when the fracture is grossly comminuted, intraarticular, or unstable.

PMID- 19753182
TI  - Free fibular strut graft in neglected femoral neck fractures in adult.
AB  - BACKGROUND: Neglected femoral neck fracture in adults still poses a formidable
      challenge. Existing treatment options varies from osteotomy (with or without
      graft) to osteosynthesis using various implants and grafting techniques (muscle
      pedicle, vascularized, and nonvascularized fibula). The aim of this study was to
      assess outcome of nonvascularized fibular strut graft and cancellous screw
      fixation in neglected femoral neck fractures in the younger age group. MATERIALS
      AND METHODS: Medical records of 32 patients of neglected femoral neck fracture,
      in the age group of 22-45 years (mean 37.8 years), operated between May 1994 to
      December 2001, were retrospectively reviewed. After the application of inclusion
      and exclusion criteria, 28 patients having three years minimum follow-up (mean
      4.6 years) were included. Delay between injury and operation varied from four
      weeks to 42 weeks (mean 16.4 weeks). Closed reduction was achieved in 17
      patients; open reduction through Watson-Jones anterolateral approach was
      performed in the remaining 15 patients in whom closed reduction failed. The
      fracture was transfixed with three parallel guide wires. Appropriate sized
      cannulated lag screw (7 mm) was then inserted in two of the wires. Selection of
      the third guide wire for fibula depended on the space available in both
      anteroposterior and lateral view. RESULTS: Satisfactory bony union was obtained
      in 25 patients, of whom in four cases, the union occurred in 10-20 degrees (mean
      15 degrees ) of varus. Nonunion occurred in three patients (9.37%), and aseptic
      necrosis occurred in another six patients (18.75%). Of the 25 patients where
      union was achieved, five patients showed excellent results; 14 good and six had
      poor functional result, as evaluated using modified Anglen criteria. CONCLUSION:
      Nonvascularized fibular strut graft along with cancellous screws provides a
      dependable and technically less-demanding alternative procedure for neglected
      femoral neck fractures in young adults. Fibula being cortical provides mechanical
      strength besides stimulating the union and getting incorporated as biological
      graft.

PMID- 19753183
TI  - Resection arthrodesis for the management of aggressive giant cell tumor of the
      distal femur.
AB  - BACKGROUND: Giant cell tumors (GCTs) of bone are aggressive benign tumors. Wide
      resection is reserved for a small subset of patients with biologically more
      aggressive, recurrent, and extensive tumors. Wide resection and mobile joint
      reconstruction are preferable for treating tumors around the knee. In certain
      situations, resection arthrodesis or an amputation is suggested. In this
      prospective study we report the outcome of 8 patients of aggressive GCT of lower
      end of femur treated with resection arthrodesis. MATERIALS AND METHODS: Eight
      patients with mean age of 37.25 years (range 30-45 years) with Campanacci Grade
      III (Enneking stage III) giant cell tumors at the distal femur were treated with
      wide resection and arthrodesis using dual free fibular graft and locked
      intramedullary nail from January 2003 to January 2008. There were four males and
      four females patients. The mean follow-up was 48.75 months (range 30-60 months).
      The functional evaluation was done using the standard system of musculoskeletal
      tumor society with its modification developed by Enneking et al. RESULTS: At the
      final follow up the functional score ranged from 20 to 27 out of total score of
      30. Graft union was achieved in all cases in a duration mean of 14.5 months
      (range 12-20 months).One case required secondary bone graft due to delayed union,
      and one case had superficial wound infection which healed on systemic
      antibiotics. At final followup, all the patients were disease free. CONCLUSION:
      Wide resection and arthrodesis in aggressive GCTs of the distal femur with
      involvement of all muscle compartments is a good treatment option. Resection
      arthrodesis offers a biological reconstruction alternative to amputation in a
      special group of patients when extensive resection precludes mobile joint
      reconstruction.

PMID- 19753184
TI  - Quantifying normal ankle joint volume: An anatomic study.
AB  - BACKGROUND: Many therapeutic and diagnostic modalities such as intraarticular
      injections, arthrography and ankle arthroscopy require introduction of fluid into
      the ankle joint. Little data are currently available in the literature regarding
      the maximal volume of normal, nonpathologic, human ankle joints. The purpose of
      this study was to measure the volume of normal human ankle joints. MATERIALS AND
      METHODS: A fluoroscopic guided needle was passed into nine cadaveric adult ankle
      joints. The needle was connected to an intracompartmental pressure measurement
      device. A radiopaque dye was introduced into the joint in 2 mL boluses, while
      pressure measurements were recorded. Fluid was injected into the joint until
      three consecutive pressure measurements were similar, signifying a maximal joint
      volume. RESULTS: The mean maximum ankle joint volume was 20.9 +/- 4.9 mL (range,
      16-30 mL). The mean ankle joint pressure at maximum volume was 142.2 +/- 13.8 mm
      Hg (range, 122-166 mm Hg). Two of the nine samples showed evidence of fluid
      tracking into the synovial sheath of the flexor hallucis longus tendon.
      CONCLUSION: Maximal normal ankle joint volume was found to vary between 16-30 mL.
      This study ascertains the communication between the ankle joint and the flexor
      hallucis longus tendon sheath. Exceeding maximal ankle joint volume suggested by
      this study during therapeutic injections, arthrography, or arthroscopy could
      potentially damage the joint.

PMID- 19753185
TI  - Mitchell's osteotomy in the management of hallux valgus: An Indian perspective.
AB  - BACKGROUND: Hallux valgus is a common condition that affects the forefoot. A
      large number of procedures are described for managing this condition. Mitchell's
      osteotomy and its modifications are being widely used for treating hallux valgus.
      However, most of the studies describe the results from the developed world. We
      present results of the classic Mitchell's osteotomy in hallux valgus in Indian
      subcontinent. MATERIALS AND METHODS: Forty eight adult patients (including 12
      bilateral ones) in the age range of 18-60 years with hallux valgus were managed
      with the classic Mitchell's osteotomy. Pain over the bunion was the reason for
      surgery in 53 of 60 feet and cosmesis in the remaining 7 feet. Patients with
      hallux valgus angle more than 20 degrees and not responding to a trial of
      conservative treatment were included. Patients having metatarsophalangeal (MTP)
      joint osteoarthritis (Grade II and higher), hallux rigidus, rheumatoid arthritis,
      and with subluxation of MTP joint were excluded from the study. Further, patients
      with first metatarsal more than 3 mm shorter than second metatarsal were also
      excluded. RESULTS: The average follow-up period is 3 yrs (range 18months - 6yrs).
      About 55 feet (83%) were painless after surgery. Forty-two (70%) patients were
      happy with the cosmetic results of the surgery. Metatarsalgia was the reason for
      dissatisfaction with the procedure in five patients. The average correction of
      hallux valgus and the intermetatarsal angles achieved was 19.7 degrees and 6.9
      degrees , respectively. Using the Broughton and Winson scoring system, 37 (61.7%)
      feet had excellent results, 18 (30%) had good, and five (8.3%) feet had a poor
      results. CONCLUSION: The classic Mitchell's procedure is a simple procedure and
      gives good cosmetic and radiological results.

PMID- 19753186
TI  - Undergraduate orthopedic education: Is it adequate?
AB  - BACKGROUND: Basic musculoskeletal knowledge is essential to the practice of
      medicine. The purpose of this study was to assess the adequacy of musculoskeletal
      knowledge of medical students. MATERIALS AND METHODS: The validated basic
      competency examination in musculoskeletal medicine devised by Freidman and
      Bernstein was administered to final year medical students just prior to their
      final professional examination. Participants were also required to assess their
      confidence at making a musculoskeletal physical examination and diagnosis as well
      as comment on the adequacy of time in the curriculum devoted to Orthopedics.
      RESULTS: The response rate was 83% (40/48). The average cognitive examination
      score was 48.3%. Two participants (5%) obtained a score of >/= 73.1%, the
      recommended mean passing score. Seventeen students (42.5%) felt orthopedic
      clinical cases were the most difficult to perform a physical examination and
      diagnose. Thirteen students (32.5%) felt that the time devoted to orthopedics in
      the medical curriculum was inadequate. CONCLUSIONS: Ninety-five percent of the
      students failed to show basic musculoskeletal competency. A change in medical
      curriculum and teaching methods is required to address this problem.

PMID- 19753187
TI  - Medial swivel dislocation of the talonavicular joint.
AB  - Medial swivel dislocation, a variant of subtalar dislocation is uncommon. A 35
      years old male presented after 6 weeks old injury to left ankle following motor
      cycle accident. He had pain, swelling around ankle and was unable to bear weight
      on left foot. Clinical examination revealed diffuse swelling and tenderness in
      mid foot region. His plain X rays and CT scan showed talonavicular dislocation
      with compression defect of the head of the talus. He was treated by open
      reduction and K-wire fixation. At 32 months follow up foot was painless, stable
      with normal range of ankle and subtalar motion.

PMID- 19753188
TI  - Management of sequalae of neglected septic shoulder.
AB  - Complex deformities following septic arthritis of the shoulder in infancy are
      mild and therefore rarely reported. A 12 year old girl presented with shortening
      of upper extremity right side, with dislocation of shoulder and with entire
      extremity rotated to 180 degrees. The palm faced posteriorly and the olecranon
      anteriorly. Arthrodesis of shoulder and unifocal lengthening of humerus was
      achieved with three 4 mm cannulated cancellous screws and an ilizarov frame. A
      lengthening of 9 centimeters was achieved and regenerate healed at 12 months. At
      10 years follow-up she is able to perfom her activities of daily living.

PMID- 19753189
TI  - Giant osteochondral body in a popliteal cyst.
AB  - Popliteal cysts, although commonly seen, are rarely associated with motion
      restriction or calcification. Radiological features are of soft-tissue swelling,
      with occasional reports of calcifications or small osteochondral bodies inside
      the cysts. We report a giant osteochondral body in a popliteal cyst, with
      significant mechanical block to flexion. This type of mass has to be
      differentiated from synovial osteochondromatosis, calcifications in the cyst,
      extraosseous and intraarticular osteochondromas. Complete excision of the cyst
      resulted in complete recovery of range of motion.

PMID- 19753190
TI  - The pelvic digit "eleventh finger".
AB  - Described as asymptomatic and an incidental finding on a plain x-ray film, the
      "pelvic digit" is a rare congenital anomaly. A 35-year-old man is of a rare
      symptomatic pelvic digit that warranted surgical excision. Its importance lies in
      its differentiation from acquired abnormalities due to trauma such as myositis
      ossificans and avulsion injuries of pelvis. If this entity is kept in mind,
      unnecessary investigations or interventions can be avoided.

PMID- 19753191
TI  - Benign self-limiting cystic lesion after lower end radius fracture in a child.
AB  - Post-traumatic cystic lesion is usually found adjacent to a healing torus
      fracture. It is typically asymptomatic and appears just proximal to the fracture
      line within the area of subperiosteal new bone formation. We report one such cyst
      in a 7 year old boy, with a brief review of literature to highlight the
      occurrence of such benign self limiting cystic lesions of lower end radius
      fracture.

PMID- 19753192
TI  - Lasers, liposuction, and the results conundrum.

PMID- 19753193
TI  - A prospective clinical review of "multi model" approach for treating ear keloids.
AB  - This is a prospective clinical study of 46 ear keloids in 31 patients (with a
      mean follow-up of 18 months) treated from January 2006 to December 2006 at The
      Queen Elizabeth Public Hospital, Barbados, West Indies by a single surgeon. The
      mean age is 21.9 years (range 3-66 years). Seven out of 46 lesions were recurrent
      lesions following previous surgery. All the lesions were excised surgically
      (extralesional). Ten out of 31 patients were given postoperative, Intralesional
      Triamcinolone starting from the 1(st) post operative visit on three visits at
      monthly intervals. Fourteen patients were given postoperative superficial X-ray
      therapy of 12 Gy in three equal fractions on three consecutive days starting from
      the 3(rd) postoperative day. Seven recurrent keloids of this study were given a
      combination of both superficial X-ray therapy and intralesional triamcinolone.
      All patients were followed at monthly intervals for three visits from the time of
      surgery and every three months until the end of the 1(st) year and then every six
      months thereafter. Five of 46 postoperative surgical wounds showed evidence of
      recurrence during the 1(st) year but could be suppressed with Intralesional
      triamcinolone. This study confirms that surgical excision of keloids supplemented
      with radiotherapy and/Intralesional triamcinolone is a reliable method with few
      complications. In addition, the study concludes that the key in preventing
      recurrence is regular clinical follow-up to encounter early recurring lesion
      (clinical evidence of raised scars or palpable nodules if deep seated) which is
      100% susceptible to Intralesional triamcinolone for 2-3 times at monthly
      intervals.

PMID- 19753194
TI  - Effects of melatonin on the proliferation and differentiation of rat adipose
      derived stem cells.
AB  - BACKGROUND: Osteogenesis driven by adipose-derived stem cells (ADSCs) is
      regulated by physiological and pathological factors. Accumulating evidence from
      in vitro and in vivo experiments suggests that melatonin may have an influence on
      bone formation. However, little is known about the effects of melatonin on
      osteogenesis, which thus remains to be elucidated. This study was performed to
      determine whether melatonin at physiological concentrations (0.01-10 nM) could
      affect the in vitro proliferation and osteogenic differentiation of rat ADSCs.
      MATERIALS AND METHODS: ADSCs were isolated from the fat of adult rats. After cell
      expansion in culture media and through three passages, osteogenesis was induced
      in a monolayer culture using osteogenic medium with or without melatonin at
      physiological concentrations (0.01-10 nM). After four weeks, the cultures were
      examined for mineralization by Alizarin Red S and von Kossa staining and for
      alkaline phosphatase (ALP) activity using an ALP kit. Cell viability and
      apoptosis were also assayed by 3-(4, 5-dimethylthiazol-2-yl)-5-(3
      carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTT) assay and flow
      cytometry, respectively. RESULTS: The results indicated that at physiological
      concentrations, melatonin suppressed proliferation and differentiation of ADSCs.
      These data indicate that ADSCs exposed to melatonin, had a lower ALP activity in
      contrast to the cells exposed to osteogenic medium alone. Similarly, mineral
      deposition (calcium level) also decreased in the presence of melatonin. Flow
      cytometry confirmed that cell growth had decreased and that the numbers of
      apoptotic cells had increased. CONCLUSION: These results suggest that the
      physiological concentration of melatonin has a negative effect on ADSC
      osteogenesis.

PMID- 19753195
TI  - Submental tracheal intubation in oromaxillofacial surgery.
AB  - BACKGROUND: Oromaxillofacial surgical procedures present a unique set of problems
      both for the surgeon and for the anesthesist. Achieving dental occlusion is one
      of the fundamental aims of most oromaxillofacial procedures. Oral intubation
      precludes this surgical prerequisite of checking dental occlusion. Having the
      tube in the field of surgery is often disturbing for the surgeon too, especially
      in the patient for whom skull base surgery is planned. Nasotracheal intubation is
      usually contraindicated in the presence of nasal bone fractures seen either in
      isolation or as a component of Le Fort fractures. We utilized submental
      endotracheal intubation in such situations and the experience has been very
      satisfying. MATERIALS AND METHODS: The technique has been used in 20 patients
      with maxillofacial injuries and those requiring Le Fort I approach with or
      without maxillary swing for skull base tumors. Initial oral intubation is done
      with a flexo-metallic tube. A small 1.5 cm incision is given in the submental
      region and a blunt tunnel is created in the floor of the mouth staying close to
      the lingual surface of mandible and a small opening is made in the mucosa. The
      tracheal end of tube is stabilized with Magil's forceps, and the proximal end is
      brought out through submental incision by using a blunt hemostat taking care not
      to injure the pilot balloon. At the end of procedure extubation is done through
      submental location only. RESULTS: The technique of submental intubation was used
      in a series of twenty patients from January 2005 to date. There were fifteen male
      patients and five female patients with a mean age of twenty seven years (range 10
      to 52). Seven patients had Le Fort I osteotomy as part of the approach for skull
      base surgery. Twelve patients had midfacial fractures at the Le Fort II level, of
      which 8 patients in addition had naso-ethomoidal fractures and 10 patients an
      associated fracture mandible. Twelve patients were extubated in the theatre.
      Eight patients had delayed extubation in the post-operative ward between 1 and 3
      days postoperatively. CONCLUSION: In conclusion, the submental intubation
      technique has proved to be a simple solution for many a difficult problem one
      would encounter during oromaxillofacial surgical procedures. It provides a safe
      and reliable route for the endotracheal tube during intubation while staying
      clear of the surgical field and permitting the checking of the dental occlusion,
      all without causing any significant morbidity for the patient. Its usefulness
      both in the emergency setting and for elective procedures has been proved. The
      simplicity of the technique with no specialized equipment or technical expertise
      required makes it especially advantageous. This technique therefore, when used in
      appropriate cases, allows both the surgeon and the anesthetist deliver a better
      quality of patient care.

PMID- 19753196
TI  - Chemical injuries from assaults: An increasing trend in a developing country.
AB  - OBJECTIVE: This paper describes chemical injuries, which presented to us and were
      managed at a burn unit in Nigeria. The purpose of this paper is to highlight the
      etiologies of these injuries, the extent of the injuries as well as to suggest
      possible ways to prevent chemical injuries in our environment. MATERIALS AND
      METHODS: We carried out a retrospective review of chemical burns treated at our
      center. Our sources of information were the burn unit admission registers, case
      notes of the patients and operation registers. The results were collated and then
      analyzed. RESULTS: Twenty eight patients presented with chemical burn injuries
      during the study period between January 2000 and December 2003, constituting 5.7%
      of all patients with burns treated within that period. Seventeen (60.7%) of the
      patients were males while 11 (29.3%) were females with a mean age of 20.6 years.
      The injuries were sustained from assault in 21 (75%), armed robbery attacks in
      five (17.8%) and suicide attempts in two (7.1%). The agents were usually unknown.
      Late presentation was observed in all the patients. Raw eggs, palm oil, gentian
      violet and engine oil were the substances applied immediately after the injuries.
      Complications observed included septicemia, respiratory distress, blindness,
      renal failure, mentosternal contractures, ectropion, axillary contractures,
      hypertrophic scars, keloids and skin depigmentation. CONCLUSION: Chemical burn
      injuries are mainly due to assaults in Nigeria and are usually extensive and
      presented late. Education of the people and penalty for any offender will reduce
      the current spate of such injuries.

PMID- 19753197
TI  - The extended latissimus dorsi flap option in autologous breast reconstruction: A
      report of 14 cases and review of the literature.
AB  - BACKGROUND: Autologous breast reconstruction using the extended latissimus dorsi
      flap has been infrequently reported. In the current study, the authors are
      reporting their own clinical experience with this method. A review of the
      literature is also discussed. MATERIALS AND METHODS: Over a three year period, 14
      patients underwent breast reconstruction using the extended latissimus dorsi (LD)
      flap. Patients with small to medium sized breasts were selected. The age of the
      patients ranged from 29 to 42 years with a follow-up period ranging from six to
      18 months. The indications, flap-related complications and donor site morbidity
      and aesthetic results were evaluated. RESULTS: The main indication to use the
      flap was dorsal donor site preference by patients. The remaining patients were
      either not suitable for a flap from the abdomen or wished to get pregnant and
      were offered the dorsal donor site. Neither total nor partial flap loss was
      recorded but donor site morbidity was mainly due to seroma, which was treated
      conservatively in all patients, except for one who required surgery. Another two
      patients suffered from wound breakdown and distal necrosis of the back flaps.
      Mild contour deformity was also noted on the back of all patients but caused no
      major concern. Indeed, the overall patient satisfaction was very high.
      CONCLUSION: The extended LD flap proved to be a good option for autologous breast
      reconstruction in selected patients. Patients should be warned of the potential
      for seroma and mild contour back deformity.

PMID- 19753198
TI  - Epidemiology of burns in a teaching hospital in south India.
AB  - Despite many medical advances, burns continue to remain a challenging problem due
      to the lack of infrastructure and trained professionals as well as the increased
      cost of treatment, all of which have an impact on the outcome. There is very
      little information on the pattern of outcomes among burn patients in relation to
      clinical aspects in India. Hence, the present study was undertaken in a burns
      unit to determine selected epidemiological variables, assess the clinical aspects
      (etiology, extent and anatomical location) and first aid measures adopted and
      finally to analyse the outcomes in cases of burn injuries. In addition, we have
      sought to suggest measures to remove myths about pre-hospital burn treatment and
      provide recommendations to healthcare professionals.

PMID- 19753200
TI  - Modified safe technique for circumcision.
AB  - We have used surgical gauze under the prepuceal skin as a pack in 20 cases prior
      to marking incision for circumcision. The prepuceal adhesions were first
      dissected and seperated. The method allows a stable, well-supported prepuceal
      surface for marking incisions and avoids injuries to the glans. Because the
      prepuceal surface is taut and stable, hemostasis is easier and quicker and the
      operating time is reduced.

PMID- 19753199
TI  - Tissue engineering approaches for the construction of a completely autologous
      tendon substitute.
AB  - Tissue engineering is a multidisciplinary field that involves the application of
      the principles and methods of engineering and life sciences towards i) the
      fundamental understanding of structure-function relationships in normal and
      pathological mammalian tissues and ii) the development of biological substitutes
      that restore, maintain or improve tissue function. The goal of tissue engineering
      is to surpass the limitations of conventional treatments based on organ
      transplantation and biomaterial implantation. The field of tendon tissue
      engineering is relatively unexplored due to the difficulty in in vitro
      preservation of tenocyte phenotype. Only recently has mechanobiology allowed us
      to gain a better understanding of the fundamental role of in vitro mechanical
      stimuli in maintaining the phenotype of tendinous tissue. This review analyzes
      the techniques used so far for in vitro regeneration of tendinous tissue.

PMID- 19753201
TI  - Silicone Foley's catheter: A useful splint in ear surgeries.
AB  - Maintenance of ear projection and post auricular sulcus in staged ear
      reconstruction in microtia is a trying problem. So also is the maintenance of the
      patency of the external auditory meatus following recanalization and meatoplasty.
      Numerous splints and dressing techniques have been described for the above
      situations. Some of the problems encountered include the availability of the
      materials, cost, expertise in fabrication and compliance. AIMS: To devise a
      simple, reliable, inexpensive and readily available splint for the maintenance of
      post auricular sulcus and external auditory meatus opening. SETTINGS AND DESIGN:
      A silicone catheter is made out of a soft and inert material that doesn't cause
      tissue necrosis or any loss of skin graft. The basic design is that of a simple,
      self-retaining type of splint that doesn't dislodge and can be prepared within
      minutes on the operating table. MATERIALS AND METHODS: This splint has been used
      in four cases of microtia reconstruction and one case of congenital external
      auditory meatus stenosis between June 2006 and August 2007. A 14 or 16 Fr
      silicone Foley's catheter was used. The proximal end of a catheter of required
      length was retained and the distal part was cut off. The catheter was looped into
      a circle around the base of the reconstructed ear and secured in position with a
      suture. A similar construct was used in cases of external auditory meatus
      reconstruction or recanalization. The funnel-shaped distal drainage end was
      sutured to the circular frame near the region of the tragus. This funnel was
      inserted into the external auditory canal. RESULTS: The catheter was found to sit
      snugly in the newly created sulcus, thereby maintaining the sulcus and ear
      projection. It aided in maintaining the meatal opening of a satisfactory diameter
      in the case of external auditory canal recanalization. It was never found to slip
      or get dislodged in any of the cases. There was no skin graft loss or tissue
      necrosis due to the use of the splint. CONCLUSIONS: The silicone Foley's catheter
      is found to be a simple, readily available, inexpensive and reliable self
      retaining splint following ear elevation in microtia and external auditory meatus
      recanalization. The catheter is easily constructed and applied intraoperatively.
      The results following its usage have been uniformly good in all cases without
      causing any adverse events at the operated site or discomfort to the patient
      ensuring good compliance.

PMID- 19753202
TI  - Reversed cross finger subcutaneous flap: A rapid way to cover finger defects.
AB  - Adequate coverage of dorsal finger wounds is often a challenge. The reversed
      cross finger subcutaneous flap to cover defects on the dorsum of phalanx
      constitutes an excellent option for coverage of wounds over the middle and distal
      phalanges of the index, middle, ring, and small fingers. It's an easy flap and
      represents our first choice to cover those defects.

PMID- 19753203
TI  - Mycobacterium fortuitum abdominal wall abscesses following liposuction.
AB  - We describe here a case of abdominal abscesses due to Mycobacterium fortuitum
      following liposuction. The abscesses developed three months after the procedure
      and diagnosis was delayed for five months. The clues for diagnosis were
      persistent pus discharge in spite of broad spectrum antibiotics and failure to
      grow any organisms on routine culture. This condition has been rarely reported;
      however, the increasing number of liposuction procedures done and awareness among
      physicians will probably result in the identification of more cases. Combination
      antibiotic therapy with surgical drainage in more extensive diseases is essential
      for cure.

PMID- 19753204
TI  - Coverage of defects over toes with distally based local flaps: A report of four
      cases.
AB  - Reconstruction of the distal foot, especially of the toe has always been a
      challenging problem. Various methods have been tried with variable success rates
      and limitations. Presented here is a series of four cases, where distally based
      flaps were used. Two of them were Extensor Digitorum Brevis (EDB) muscle flaps
      and the other two were first dorsal metatarsal artery (FDMA) based skin flaps.
      One in each of the two was augmented with a plantar V-Y advancement flap. All
      flaps survived completely without any flap- or donor site-related complications.
      The patients were ambulated two weeks following the reconstruction and were
      symptom-free after an average follow-up of thirteen months. Distal flaps based on
      the dorsalis pedis system provide a reliable cover for distal foot defects.

PMID- 19753205
TI  - Total excision and V-Y plasty technique in the anal area condyloma acuminatum.
AB  - Condyloma acuminatum is located in the perianal region, anal canal, vagina and
      the perineum. It is caused by human papillomavirus types 6 and 11. A 18 year-old
      man was admitted to the clinic because of a perianal mass. On examination of the
      patient's perianal area and inside the anal canal, a mass was found, which was
      nearly 8 x 8 cm in size. We could not obtain any information about venereal
      transmission. The mass was totally excised and the defect was reconstructed with
      a bilateral V-Y advancement flap. This technique has been used for
      sacrococcygeal, ischial and other defects but rarely used for condyloma
      acuminatum. We think that total excision and the use of the V-Y advancement flap
      technique is safe and has low morbidity in the treatment of condyloma acuminatum.

PMID- 19753206
TI  - An interesting case of familial chylomicronemia syndrome in a cleft palate child.
AB  - Familial chylomicronemia syndrome is a very rare condition with an incidence of
      one in one million. We report such a condition detected incidentally in a cleft
      child.

PMID- 19753207
TI  - Ulnar nerve palsy after open carpal tunnel decompression: Case report and review
      of the literature.
AB  - Open carpal tunnel release is the commonest surgical treatment of median nerve
      compression at the wrist. Although successful in most cases, there are well
      described complications. We report a case of laceration of the deep motor branch
      of the ulnar nerve at the level of the hook of hamate following a complicated
      carpal tunnel decompression. Good surgical technique and knowledge of wrist
      anatomy are essential for performing this apparently simple procedure safely.

PMID- 19753208
TI  - Radial, renal and craniofacial anomalies: Baller-Gerold syndrome.
AB  - The Baller-Gerold syndrome is a rare syndrome with very few cases published in
      literature. Craniosynostosis and radial aplasia are striking features, easy to
      diagnose. However, there are many differential diagnoses. Often, the question
      raised is whether the Baller-Gerald syndrome is a distinct entity. We report a
      patient with findings of craniosynostosis and radial aplasia consistent with the
      diagnosis of the Baller-Gerold syndrome. Genotypic heterogeneity could possibly
      underlie the phenotypic variability exhibited by these cases.

PMID- 19753209
TI  - Use of Foley catheter as a flap retainer.
AB  - Keeping skin graft or a flap adherent to the underlying surface can sometimes be
      a difficult job, particularly inside a cavity. Different methods have been used
      for this function with varying success but the search is still on for an ideal
      pressure dressing.

PMID- 19753210
TI  - Progressive skin necrosis of a huge occipital encephalocele.
AB  - OBJECTS: Progressive skin necrosis of giant occipital encephalocoele is an
      extremely rare complication found in neonates. Infection and ulceration of the
      necrosed skin may lead to meningitis or sepsis. We present here a neonate with
      giant occipital encephalocoele showing progressive necrosis during the first day
      of his life. METHODS: A newborn baby was found to have a huge mass in the
      occipital region, which was covered by normal pink-purplish skin. During the last
      hours of the first day of his life, the sac started becoming ulcerated
      accompanied with a rapid color change in the skin, gradually turning darker and
      then black. The neonate was taken up for urgent excision and repair of the
      encephalocele. Two years after the operation, he appears to be well-developed
      without any neurological problems. CONCLUSION: Necrosis may have resulted from
      arterial or venous compromise caused by torsion of the pedicle during delivery or
      after birth. The high pressure inside the sac associated with the thin skin of
      the encephalocoele may be another predisposing factor. In view of the risk of
      ulceration and subsequent infection, urgent surgery of the necrotizing
      encephalocele is suggested.

PMID- 19753211
TI  - Trifurcation of the right common carotid artery.
AB  - Variations in the position of the bifurcation of the common carotid artery and
      the origin or branching pattern of the external carotid artery are well known and
      documented. Here, we report the trifurcation of the right common carotid artery
      in a male cadaver aged about 55 years. The right common carotid artery was found
      to divide into the external and internal carotids and the occipital artery. High
      division of bilateral common carotid arteries and a lateral position of the right
      external carotid artery at its origin were also observed in the same cadaver.
      There were two ascending pharyngeal arteries on the right side - one from the
      occipital artery and another from the internal carotid artery. The intraarterial
      approach is one of the most important routes for the administration of anticancer
      drugs for head and neck cancers. A profound knowledge of the anatomical
      characteristics and variations of the carotid artery such as its branching
      pattern and its position is essential to avoid complications with catheter
      insertion.

PMID- 19753212
TI  - Historical remarks on Martin Kirschner and the development of the Kirschner (K)
      wire.

PMID- 19753214
TI  - Case reports.

PMID- 19753213
TI  - Challenges to current medical education and practice.

PMID- 19753215
TI  - Unusual palmaris longus muscle.

PMID- 19753216
TI  - Unusual presentation of a foreign body in the palate.

PMID- 19753217
TI  - Giant fibrolipoma mimicking abdominal lipodystrophy.

PMID- 19753218
TI  - A useful technique to maintain the position of the hand following abdominal flap
      cover.

PMID- 19753219
TI  - A mathematical model to predict the requirement for multiple Z plasties.

PMID- 19753220
TI  - A simple method to maintain immobilization and elevation of the hand in infants
      and children.

PMID- 19753221
TI  - The idea called India.

PMID- 19753222
TI  - Open fractures.

PMID- 19753223
TI  - The utility of scores in the decision to salvage or amputation in severely
      injured limbs.
AB  - The decision to amputate or salvage a severely injured limb can be very
      challenging to the trauma surgeon. A misjudgment will result in either an
      unnecessary amputation of a valuable limb or a secondary amputation after failed
      salvage. Numerous scores have been proposed to provide guidelines to the treating
      surgeon, the notable of which are Mangled extremity severity score (MESS); the
      predictive salvage index (PSI); the Limb Salvage Index (LSI); the Nerve Injury,
      Ischemia, Soft tissue injury, Skeletal injury, Shock and Age of patient (NISSSA)
      score; and the Hannover fracture scale-97 (HFS-97). These scores have all been
      designed to evaluate limbs with combined orthopaedic and vascular injuries and
      have a poor sensitivity and specificity in evaluating IIIB injuries. Recently the
      Ganga Hospital Score (GHS) has been proposed which is specifically designed to
      evaluate a IIIB injury. Another notable feature of GHS is that it offers
      guidelines in the choice of the appropriate reconstruction protocol. The basis of
      the commonly used scores with their utility have been discussed in this paper.

PMID- 19753225
TI  - Pearls and tips in coverage of the tibia after a high energy trauma.
AB  - Coverage of soft-tissue defects in the lower limbs, especially open tibial
      fractures, is currently a frequently done procedure because of the high incidence
      of high-energy trauma, which affects this location. The skilled orthopedic
      surgeon should be able to carry out an integral treatment of these lesions, which
      include not only the open reduction and internal fixation of the fracture
      fragments but also the management of complications such as local wound problems
      that may arise. There is a wide variety of muscular or pedicled flaps available
      for reconstruction of lower limb soft-tissue defects. These techniques are not
      commonly used by orthopedic surgeons because of the lack of familiarity with them
      and the potential for flap failure and problems derived from morbidity of the
      donor site. We present a coverage management update for orthopedic surgeons for
      complications after an open tibial fracture. We choose and describe the most
      adequate flap depending on the region injured and the reliable surgical
      procedure. For proximal third of the tibia, we use gastrocnemius muscle flap.
      Middle third of the tibia could be covered by soleus muscle flap. Distal third of
      the tibia could be reconstructed by sural flaps, lateral supramalleolar skin
      flap, and posterior tibial perforator flap. Free flaps can be used in all
      regions. We describe the advantages and disadvantages, pearls, and tips of every
      flap. The coverage of the tibia after a major injury constitutes a reliable and
      versatile technique that should form part of the therapeutic arsenal of all the
      orthopedic surgeons, facilitating the integral treatment of complex lower limb
      injuries with exposed defects.

PMID- 19753224
TI  - Treatment principles in the management of open fractures.
AB  - The management of open fractures continues to provide challenges for the
      orthopedic surgeon. Despite the improvements in technology and surgical
      techniques, rates of infection and nonunion are still troublesome. Principles
      important in the treatment of open fractures are reviewed in this article. Early
      antibiotic administration is of paramount importance in these cases, and when
      coupled with early and meticulous irrigation and debridement, the rates of
      infection can be dramatically decreased. Initial surgical intervention should be
      conducted as soon as possible, but the classic 6 h rule does not seem to be
      supported in the literature. All open fractures should be addressed for the risk
      of contamination from Clostridium tetani. When possible, early closure of open
      fracture wounds, either by primary means or by flaps, can also decrease the rate
      of infection, especially from nosocomial organisms. Early skeletal stabilization
      is necessary, which can be accomplished easily with temporary external fixation.
      Adhering to these principles can help surgeons provide optimal care to their
      patients and assist them in an early return to function.

PMID- 19753226
TI  - Management of open fractures of the tibial shaft in multiple trauma.
AB  - BACKGROUND: The work presents the assessment of the results of treatment of open
      tibial shaft fractures in polytrauma patients. MATERIALS AND METHODS: The study
      group comprised 28 patients who underwent surgical treatment of open fractures of
      the tibial shaft with locked intramedullary nailing. The mean age of the patients
      was 43 years (range from 19 to 64 years). The criterion for including the
      patients in the study was concomitant multiple trauma. For the assessment of open
      tibial fractures, Gustilo classification was used. The most common concomitant
      multiple trauma included craniocerebral injuries, which were diagnosed in 12
      patients. In 14 patients, the surgery was performed within 24 h after the injury.
      In 14 patients, the surgery was delayed and was performed 8-10 days after the
      trauma. RESULTS: The assessment of the results at 12 months after the surgery
      included the following features: time span between the trauma and the surgery and
      complications in the form of osteomyelitis and delayed union. The efficacy of
      gait, muscular atrophy, edema of the operated limb and possible disturbances of
      its axis were also taken under consideration. In patients operated emergently
      within 24 h after the injury, infected nonunion was observed in three (10.8%)
      males. These patients had grade III open fractures of the tibial shaft according
      to Gustilo classification. No infectious complications were observed in patients
      who underwent a delayed operation. CONCLUSION: Evaluation of patients with open
      fractures of the tibial shaft in multiple trauma showed that delayed
      intramedullary nailing performed 8-10 days after the trauma, resulted in good
      outcome and avoided development of delayed union and infected nonunion. This
      approach gives time for stabilization of general condition of the patient and
      identification of pathogens from wound culture.

PMID- 19753227
TI  - Incidence of infection after early intramedullary nailing of open tibial shaft
      fractures stabilized with pinless external fixators.
AB  - BACKGROUND: A major drawback of conventional fixator system is the penetration of
      fixator pins into the medullary canal. The pins create a direct link between the
      medullary cavity and outer environment, leading to higher infection rates on
      conversion to intramedullary nailing. This disadvantage is overcome by the AO
      pinless fixator, in which the trocar points are clamped onto the outer cortex
      without penetrating it. This study was designed to evaluate the role of AO
      pinless fixators in primary stabilization of open diaphyseal tibial fractures
      that received staged treatment because of delayed presentation or poor general
      condition. We also analyzed the rate of infection on early conversion to
      intramedullary nail. MATERIALS AND METHODS: This study is a retrospective review
      of 30 open diaphyseal fractures of tibia, which were managed with primary
      stabilization with pinless fixator and early exchange nailing. Outcome was
      evaluated in terms of fracture union and rate of residual infection. The data
      were compared with that available in the literature. RESULTS: All the cases were
      followed up for a period of 2 years. The study includes Gustilo type 1 (n=10), 14
      Gustilo type 2 (n=14), and type3 (n=6) cases. 6 cases (20%) had clamp site
      infection, 2 cases (6.7%) had deep infection, and in 28 cases (93%) the fracture
      healed and consolidated well. CONCLUSION: This study has highlighted the valuable
      role of pinless external fixator in the management of open tibial fractures in
      terms of safety and ease of application as well as the advantage of early
      conversion to intramedullary implant without the risk of deep infection.

PMID- 19753228
TI  - Immediate versus delayed intramedullary nailing for open fractures of the tibial
      shaft: a multivariate analysis of factors affecting deep infection and fracture
      healing.
AB  - BACKGROUND: The purpose of this study was to evaluate contributing factors
      affecting deep infection and fracture healing of open tibia fractures treated
      with locked intramedullary nailing (IMN) by multivariate analysis. MATERIALS AND
      METHODS: We examined 99 open tibial fractures (98 patients) treated with
      immediate or delayed locked IMN in static fashion from 1991 to 2002. Multivariate
      analyses following univariate analyses were derived to determine predictors of
      deep infection, nonunion, and healing time to union. The following predictive
      variables of deep infection were selected for analysis: age, sex, Gustilo type,
      fracture grade by AO type, fracture location, timing or method of IMN, reamed or
      unreamed nailing, debridement time (< or =6 h or >6 h), method of soft-tissue
      management, skin closure time (< or =1 week or >1 week), existence of polytrauma
      (ISS< 18 or ISS> or =18), existence of floating knee injury, and existence of
      superficial/pin site infection. The predictive variables of nonunion selected for
      analysis was the same as those for deep infection, with the addition of deep
      infection for exchange of pin site infection. The predictive variables of union
      time selected for analysis was the same as those for nonunion, excluding of
      location, debridement time, and existence of floating knee and superficial
      infection. RESULTS: Six (6.1%; type II Gustilo n=1, type IIIB Gustilo n=5) of the
      99 open tibial fractures developed deep infections. Multivariate analysis
      revealed that timing or method of IMN, debridement time, method of soft-tissue
      management, and existence of superficial or pin site infection significantly
      correlated with the occurrence of deep infection (P< 0.0001). In the immediate
      nailing group alone, the deep infection rate in type IIIB + IIIC was
      significantly higher than those in type I + II and IIIA (P = 0.016). Nonunion
      occurred in 17 fractures (20.3%, 17/84). Multivariate analysis revealed that
      Gustilo type, skin closure time, and existence of deep infection significantly
      correlated with occurrence of nonunion (P < 0.05). Gustilo type and existence of
      deep infection were significantly correlated with healing time to union on
      multivariate analysis (r(2) = 0.263, P = 0.0001). CONCLUSION: Multivariate
      analyses for open tibial fractures treated with IMN showed that IMN after EF
      (especially in existence of pin site infection) was at high risk of deep
      infection, and that debridement within 6 h and appropriate soft-tissue
      managements were also important factor in preventing deep infections. These
      analyses postulated that both the Gustilo type and the existence of deep
      infection is related with fracture healing in open fractures treated with IMN. In
      addition, immediate IMN for type IIIB and IIIC is potentially risky, and canal
      reaming did not increase the risk of complication for open tibial fractures
      treated with IMN.

PMID- 19753229
TI  - Appraisal of the role of external skeletal fixation in the management of sequelae
      of open tibial fractures.
AB  - BACKGROUND: Severe open tibial fractures are more apt to be followed by
      complications even with the universally accepted lines of treatment. The present
      study investigated the role of external skeletal fixation, based on Ilizarov
      techniques, in the management of the sequelae of open tibial fractures with
      modifications to meet the requirements of each case. MATERIALS AND METHODS: We
      reviewed the results of treatment of 148 cases of late presentation with
      complicated open tibial fractures. Their ages ranged from 12 to 74 years
      (average, 34 years). Active infection was present in 40 cases. We performed acute
      shortening and relengthening in 60 cases; excision of nonunion, acute deformity
      correction, and lengthening for nonunion with deformity in 30 cases; segmental
      excision and bone transport in 20 cases; gradual deformity correction after
      osteotomy in 15 cases; and distraction and gradual deformity correction for
      hypertrophic nonunion with deformity in 23 cases. Ilizarov external fixator was
      used in 96 (65%) cases, and monolateral fixator was used in 52 (35%) cases. The
      mean follow-up was 35 months (range 24 to 118 months). RESULTS: Fracture union
      was achieved in all cases (100%). Evaluation of results were based on both
      objective (clinical and radiological) and subjective criteria and patients'
      satisfaction. The results were satisfactory in 139 cases (94%) and unsatisfactory
      in nine (6%) cases because of residual leg length discrepancy, joint stiffness,
      and persistent pain. CONCLUSIONS: The use of external fixation, based on Ilizarov
      techniques, is invaluable in the management of difficult open tibia fractures.
      However, the technique should be tailored to the requirements of each case. The
      functional outcome is predetermined by the soft tissue status before treatment.

PMID- 19753230
TI  - Utilization of the less-invasive stabilization system internal fixator for open
      fractures of the proximal tibia: a multi-center evaluation.
AB  - BACKGROUND: Locked plating has become popular and has clear biomechanical
      advantages when compared with conventional plating. When combined with minimally
      invasive surgical techniques, locked plating may cause substantially less
      iatrogenic tissue damage when compared with conventional plating. These
      characteristics may make locked plating an attractive option for treating open
      fractures of the tibial plateau and proximal tibia for which coverage over the
      plate can be obtained. The purpose of this study was to evaluate the use of the
      Less-Invasive Stabilization System (LISS) for high-energy open fractures
      involving either the tibial plateau or proximal tibia. MATERIALS AND METHODS:
      This study is a retrospective evaluation of a consecutive multicenter series of
      52 consecutive patients operated by seven surgeons, who used LISS plating in open
      proximal tibia or tibial plateau fractures seen at one of four Level I Trauma
      Centers. All patients were treated using a locked plating system that was
      implanted using minimally invasive submuscular surgical techniques. The primary
      outcome measure was the incidence of deep and superficial infection. RESULTS:
      Fifty-two patients with open fractures have been evaluated, with a mean follow-up
      of 16.8 (12-36) months. Three patients (5.8%) developed deep infections. Two
      patients (6.3%) with tibial plateau and one (4.3%) of patients with a tibial
      shaft fracture developed deep infections. Fifteen patients required flap coverage
      of their open wounds. The incidence of deep infection as per Gustilo and Anderson
      classification was Type I and II - 0 (0%); Type IIIA - 2 (7.7%); Type IIIB - 1
      (7.1%); and Type IIIC - 0 (0%). CONCLUSIONS: Biomechanically, the LISS functions
      as an "internal-external fixator" rather than a plate. Traditional plate
      osteosynthesis has yielded rates of infection between 18% and 35%. Our data
      indicate that locked plating using minimally invasive techniques yield deep
      infections rates that are no worse than published series using intramedullary
      nails or external fixators. Technical difficulties that can be encountered with
      the LISS system revolve primarily around obtaining and maintaining reduction
      while performing a minimally invasive procedure. Additional difficulties can
      include "cold welding" of screws to the plate and malposition of the plate
      leading to failure in the diaphysis. High-energy open fractures involving the
      tibia shaft or plateau remain high-risk injuries, but LISS is an acceptable
      alternative for treatment of these fractures.

PMID- 19753231
TI  - Taylor spatial frame in the treatment of open tibial shaft fractures.
AB  - BACKGROUND: The Taylor spatial frame (TSF) is a modern multiplanar external
      fixator that combines the ease of application and computer accuracy in the
      reduction of fractures. A retrospective review of our prospective TSF database
      for the use of this device for treating open tibial fractures in pediatric,
      adolescent, and adult patients was carried out to determine the effectiveness and
      complications of TSF in the treatment of these fractures. MATERIALS AND METHODS:
      Nineteen male patients with open tibial fractures were included. Of these
      fractures, 10 were Gustilo Type II, five were Gustilo Type IIIA (two had delayed
      primary closure and three had split thickness skin grafting), and four were
      Gustilo Type IIIB (all had rotational flaps). Twelve of our patients presented
      immediately to the emergency room, and the remaining seven cases presented at a
      mean of 3 months (range, 2.2-4.5 months) after the initial injury. The fractures
      were located in proximal third (n=1), proximal/middle junction (n=2), middle
      third (n=3), middle/distal junction (n=8), distal third (n=3), and segmental
      fractures (n=2). Patients were of an average age of 26 years (range, 6-45years).
      Mean duration of follow-up was 3.5 years. RESULTS: All fractures healed over a
      mean of 25 weeks (range, 9-46 weeks). All were able to participate in the
      activities of daily living without any difficulty and most were involved in
      sports during the last follow-up. Postoperative complications included pin tract
      infection in 12 patients. CONCLUSION: The TSF is an effective definitive method
      of open tibial fracture care with the advantage of early mobilization, ease of
      soft tissue management through gradual fracture reduction, and the ability to
      postoperatively manipulate the fracture into excellent alignment.

PMID- 19753232
TI  - Cross-leg flap: Its role in limb salvage.
AB  - BACKGROUND: Pedicled cross-extremity flaps for lower limb wound coverage have
      been replaced by free tissue transfer in the last two decades. However, there are
      certain difficult situations where the free flap cannot be employed and
      alternative methods are needed. We describe our experience with cross-leg flap in
      18 patients for the reconstruction of difficult leg defects in which no suitable
      recipient vessels were available for microvascular anastomosis in the vicinity of
      the defect. MATERIALS AND METHODS: 18 patients (17 men and 1 woman) with mean
      range 31.5 yrs(range 18-70 yrs) grade III B tibial fractures were included in the
      study. fasciocuteneous cross leg flap was employed and extremities were
      immobilized by external Fixator. RESULTS: Fifteen flaps were completely available
      with two had marginal necrosis and one supsficial epidermal necrosis. No
      complications were related to the donor site, flap, or by immobilization are
      noted. Each patient resumed essentially normal gait and activity without any
      stiffness of joints related with the flap or external fixator. CONCLUSION: The
      addition of external fixator stabilization aids greatly in wound care, as well as
      for general ease of the patient mobility and positioning. Cross-leg flap offers
      the possibility of salvaging limbs that are otherwise nonreconstructable.

PMID- 19753233
TI  - Therapeutic ultrasound in fracture healing: The mechanism of osteoinduction.
AB  - BACKGROUND: Ultrasound has been used therapeutically for accelerating fracture
      healing since many years. However, the controversy on the exact mechanism of
      osteoinduction still continues. In this study, we try to bring out the exact
      biomolecular mechanism by which ultrasound induces fracture healing. MATERIALS
      AND METHODS: THE STUDY WAS CONDUCTED IN TWO PHASES: animal experiments and
      clinical study. In the first phase, we induced fractures on the left tibia of
      Wistar strain rats under anaesthesia. They were divided into two groups. One of
      the groups was given low-intensity, pulsed ultrasound (30 MW/cm(2)) 20 min a day
      for 10 days. Tissue samples and radiographs were taken weekly for 3 weeks from
      both the groups. In the second phase of our study, ten patients with fractures of
      the distal end of the radius (ten fractures) were included. Five of these were
      treated as cases, and five were treated as controls. Ultrasound was given 30
      MW/cm(2) for 20 min every day for 2 weeks. The patients were assessed
      radiologically and sonologically before and after ultrasound therapy. Tissue
      samples were studied with thymidine incorporation test with and without adding
      various neurotransmitter combinations. RESULTS: Radiological findings revealed
      that there was an increased callus formation in the ultrasound group. At the
      cellular level, there was an increased thymidine incorporation in the ultrasound
      group. When various neurotransmitters were added to the cells, there was an
      increased thymidine incorporation in the ultrasound group. In the second phase of
      the study, radiological and sonological assessments showed that there was an
      increased callus formation in the ultrasound group. In cytological study,
      thymidine incorporation was found to be increased in the ultrasound group.
      CONCLUSIONS: The results of animal and clinical studies demonstrated an early and
      increased callus formation in the ultrasound group. Cytological studies revealed
      increased thymidine incorporation, suggesting increased osteoblastic activity.

PMID- 19753234
TI  - Single-stage multilevel soft-tissue surgery in the lower limbs with spastic
      cerebral palsy: Experience from a rehabilitation unit.
AB  - BACKGROUND: To assess the effect of single-stage multilevel soft-tissue surgery
      (Single Event Multiple Level Resections, SEMLR) on deformities and locomotion in
      patients with cerebral palsy (CP) with static contracture(s) in lower limbs.
      PATIENTS AND METHODS: Study included 34 patients (M:F, 23:11) with mean age of
      9.53 +/- 3.92 years (4-16 years). Among them 22 had diplegia and four each had
      quadriplegia and right and left hemiplegia. Fourteen patients (41.2%) had their
      intelligence quotient (IQ) in the normal range (IQ >/= 80), while others had
      mental retardation (MR) of varying severity: borderline MR (IQ = 70-79) in 12,
      mild MR (IQ = 50-69) in 5, and moderate MR (IQ = 35-49) in patients 3. All
      patients underwent surgery (total number of procedures 153, average 4.5
      procedures/patient) over a period of 30 months (April 2005 to September 2007).
      Improvement in functional abilities and locomotion was assessed using Gross Motor
      Functional Classification Scale (GMFCS) scores and by physical examination.
      RESULTS: Significant improvement in function was observed (P = 0.000) after
      surgery when comparing the preoperative and postoperative GMFCS scores. All
      patients were maintaining ambulation at a mean follow-up duration of 13.12 +/-
      6.07 months (3-24 months), with five patients using knee-ankle-foot orthoses
      (KAFO), 22 using ankle-foot orthoses (AFO), and six patients using knee gaiters.
      Sixteen patients were using walker, and two were using crutches as assistive
      devices. CONCLUSION: This study suggests that CP patients with good trunk control
      and static contractures at multiple joints in the lower limbs can be made
      ambulant with single-stage multilevel soft-tissue surgery. It has to be a team
      effort of the surgeon and the rehabilitation team in the postoperative period for
      the attainment of satisfactory goal.

PMID- 19753235
TI  - Paraplegia of late onset in adolescents with healed childhood caries of dorsal
      spine: A cause of pressure on the cord and treatment.
AB  - BACKGROUND: Paraplegia of late onset in adolescents with caries of dorsal spine
      is considered to be due to the reactivation of infection. Internal salient at the
      level of acute kyphotic deformity of the dorsal spine is formed by posterior
      cartilaginous remains of grossly destroyed vertebral bodies. The author presents
      a study of eight adolescent patients with paraplegia of late onset associated
      with severe kyphotic deformity of dorsal spine with observations on the cause of
      paraplegia, the final neurological outcome following anterior decompression and
      its prevention. MATERIALS AND METHODS: Eight adolescent patients mean age 14.4
      yrs 6 males and 2 females with healed childhood caries of dorsal spine, having a
      mean kyphotic angle of 80 degrees (range 60 degrees -140 degrees ) presented with
      paraplegia of late onset. Of these patients, two had medical research council
      grade 0 muscle power; four had grade 2 muscle power, and two others had grade 3
      muscle power in the lower limbs and were unable to walk unaided. One patient with
      140 degrees kyphoscoliotic deformity with grade 3 muscle power had post-polio
      residual paralysis (PPRP) in addition. All patients were subjected to thorough
      anterior spinal decompression through transthoracic, transpleural thoracotomy
      from the left side. RESULTS: In six of the eight patients, the spine at the site
      of deformity being very rigid, the deformity could not be corrected and the
      intervertebral gap was bridged with appropriate autogenous tricortical cortico
      cancelluous bone graft. In one patient (case 4), the kyphotic deformity could be
      corrected by 50%. In one patient with 140 degrees kyphosis and PPRP, the gap
      after the decompression of cord, could not be bridged with bone graft and was
      given a custom made, well molded plastic black shell to wear while walking and,
      in particular, while traveling in a vehicle. In all seven patients, bone grafts
      took six months for bridging the intervertebral gaps. All patients recovered to
      grade 4 muscle power 6-12 months after surgery. CONCLUSION: In adolescents with
      healed caries of dorsal spine with acute kyphosis and paraplegia, the treatment
      of choice is anterior surgical decompression of the cord and bridging the gap
      thus created with bone graft.

PMID- 19753236
TI  - Three-level anterior cervical discectomy and fusion in elderly patients with
      wedge shaped tricortical autologous graft: A consecutive prospective series.
AB  - BACKGROUND: Treatment of multilevel cervical spondylotic myelopathy/radiculopathy
      is a matter of debate, more so in elderly patients due to compromised physiology.
      We evaluated the clinical and radiological results of cervical fusion, using
      wedge-shaped tricortical autologous iliac graft and Orion plate for three-level
      anterior cervical discectomy in elderly patients. MATERIALS AND METHODS: Twelve
      elderly patients with mean age of 69.7 years (65-76 years) were treated between
      April 2000 and March 2005, for three-level anterior cervical discectomy and
      fusion, using wedge-shaped tricortical autologous iliac graft and Orion plate.
      Outcome was recorded clinically according to Odom's criteria and radiologically
      in terms of correction of lordosis angle and intervertebral disc height span at
      the time of bony union. The mean follow-up was 29.8 months (12-58 months).
      RESULTS: All the patients had a complete recovery of clinical symptoms after
      surgery. Postoperative score according to Odom's criteria was excellent in six
      patients and good in remaining six. Bony union was achieved in all the patients
      with average union time of 12 weeks (8-20 weeks). The mean of sum of three
      segment graft height collapse was 2.50 mm (SD = 2.47). The average angle of
      lordosis was corrected from 18.2 degrees (SD = 2.59 degrees ) preoperatively to
      24.9 degrees (SD = 4.54 degrees ) at the final follow-up. This improvement in the
      radiological findings is statistically significant (P < 0.05). CONCLUSION:
      Cervical fusion with wedge-shaped tricortical autologous iliac graft and Orion
      plate for three-level anterior cervical discectomy is an acceptable technique in
      elderly patients. It gives satisfactory results in terms of clinical outcome,
      predictable early solid bony union, and maintenance of disc space height along
      with restoration of cervical lordosis.

PMID- 19753237
TI  - Lateral closed wedge osteotomy for cubitus varus deformity.
AB  - BACKGROUND: Lateral closed wedge (LCW) osteotomy is a commonly accepted method
      for the correction of the cubitus varus deformity. The fixation of osteotomy is
      required to prevent loss of correction achieved. The fixation of the osteotomy by
      the two screw and figure of eight wire is not stable enough to maintain the
      correction achieved during surgery. In this prospective study we supplemented the
      fixation by Kirschner's (K-) wires for stable fixation and evaluated the results.
      MATERIALS AND METHODS: Twenty-one cases of the cubitus varus deformity following
      supracondylar fractures of the humerus were operated by LCW osteotomy during
      February 2001 to June 2006. The mean age of the patients at the time of
      corrective surgery was 8.5 years (range 6.6-14 years). The osteotomy was fixed by
      two screws with figure of eight tension band wire between them and the fixation
      was supplemented by passing two to three K-wires from the lateral condyle
      engaging the proximal medial cortex through the osteotomy site. RESULT: The mean
      follow-up period was 2.5 years (range seven months to 3.4 years). The results
      were assessed as per Morrey criteria. Eighteen cases showed excellent results and
      three cases showed good results. Two cases had superficial pin tract infection.
      CONCLUSION: The additional fixation by K wires controls rotational forces
      effectively besides angulation and translation forces and maintains the
      correction achieved peroperatively.

PMID- 19753238
TI  - Radiation exposure from fluoroscopy during fixation of hip fracture and fracture
      of ankle: Effect of surgical experience.
AB  - BACKGROUND: Over the years, there has been a tremendous increase in the use of
      fluoroscopy in orthopaedics. The risk of contracting cancer is significantly
      higher for an orthopedic surgeon. Hip and spine surgeries account for 99% of the
      total radiation dose. The amount of radiation to patients and operating surgeon
      depends on the position of the patient and the type of protection used during the
      surgery. A retrospective study to assess the influence of the radiation exposure
      of the operating surgeon during fluoroscopically assisted fixation of fractures
      of neck of femur (dynamic hip screw) and ankle (Weber B) was performed at a
      district general hospital in the United Kingdom. MATERIALS AND METHODS: Sixty
      patients with undisplaced intertrochanteric fracture were included in the hip
      group, and 60 patients with isolated fracture of lateral malleolus without
      communition were included in the ankle group. The hip and ankle groups were
      further divided into subgroups of 20 patients each depending on the operative
      experience of the operating surgeon. All patients had fluoroscopically assisted
      fixation of fracture by the same approach and technique. The radiation dose and
      screening time of each group were recorded and analyzed. RESULTS: The radiation
      dose and screening time during fluoroscopically assisted fixation of fracture
      neck of femur were significantly high with surgeons and trainees with less than 3
      years of surgical experience in comparison with surgeons with more than 10 years
      of experience. The radiation dose and screening time during fluoroscopically
      assisted fixation of Weber B fracture of ankle were relatively independent of
      operating surgeon's surgical experience. CONCLUSION: The experience of operating
      surgeon is one of the important factors affecting screening time and radiation
      dose during fluoroscopically assisted fixation of fracture neck of femur. The use
      of snapshot pulsed fluoroscopy and involvement of senior surgeons could
      significantly reduce the radiation dose and screening time.

PMID- 19753239
TI  - Robinow syndrome.
AB  - Robinow syndrome is a rare autosomal recessive mesomelic dwarfism with just more
      than 100 cases reported in the literature so far. The lower extremity is spared
      with skeletal deformity usually confined to the forearm, hand, and the dorsal
      spine. Diagnosis is made easily in the early childhood by the typical "fetal
      facies" appearance, which disappears to a certain extent as the patient grows.
      The author reports two cases of this entity with vertebral segmentation defects,
      rib fusion, and typical severe brachymelia and facial features.

PMID- 19753240
TI  - Pseudoachondroplasia: A rare cause of rhizomelic dwarfism.
AB  - Pseudoachondroplasia is a rare rhizomelic short-limbed skeletal dysplasia. Its
      inheritance is varied; autosomal dominant pattern and germline or somatic
      mutations can occur. Children at 2-3 years of age present with short height, gait
      disturbances, or limb deformities. Characteristic skeletal changes include
      shortening of long bones, predominantly of femur and humerus with irregular,
      flared metaphysis and fragmented epiphysis. Platyspondyly is also present, but
      the interpedicular distance is normal. The diagnosis is essentially based on
      imaging, and thus, it is important to be aware of the radiological features.
      Here, we report a case of two brothers where the elder sibling had classical
      radiological features of pseudoachondroplasia, whereas the younger one had early
      changes of this disorder.

PMID- 19753241
TI  - Intervertebral disc calcification in a child.
AB  - Disc calcification in children is a rare condition of which only approximately
      200 cases have been reported worldwide and one from India and we report one such
      case. A five year-old boy presented with neck pain, torticollis and limitations
      of cervical motions following a fall while playing 3 months back. He had low
      grade fever cervical lymphadenopthy, paraspinal muscle spasm. His blood counts
      and ESR was raised. Fine needle aspiration cytology of lymph node revealed
      reactive lymphadenitis. His cervical radiograph slowed calcification of C 6-7.
      MRI scan showed hypointense signals in C6-C7 and D5-D6 disc on both T1 and T2 W
      images. Cerebrospinal fluid examination was normal. He improved on analgesics,
      bed rest and cervical traction.

PMID- 19753242
TI  - Authors' reply.

PMID- 19753243
TI  - Prosthetic replacement in femoral neck fracture in the elderly.

PMID- 19753244
TI  - Teaching-learning and patient care.

PMID- 19753245
TI  - Past, present and future of IOA from my eyes and mind.

PMID- 19753246
TI  - Farewell.

PMID- 19753247
TI  - Patient satisfaction and ethics in a public hospital practice.

PMID- 19753248
TI  - Use of vascularised cartilage as an additional interposition in temporomandibular
      ankylosis surgery: Rationale, advantages and potential benefits.
AB  - CONTEXT: Surgery for the release of temporomandibular joint (TMJ) ankylosis is a
      commonly performed procedure. Various interposition materials have been tried
      with varying success rates. However, none of these procedures attempt to recreate
      the architecture of the joint as the glenoid surface is usually left raw. AIMS:
      We aimed to use a vascularised cartilage flap and to line the raw surface of the
      bone to recreate the articular surface of the joint. SETTINGS AND DESIGN: There
      is a rich blood supply in the region of the helical root, based on branches from
      the Superficial Temporal Artery (STA), which enables the harvest of vascularised
      cartilage from the helical root for use in the temporomandibular joint. MATERIALS
      AND METHODS: Two cases, one adult and the other a child, of unilateral ankylosis
      were operated upon using this additional technique. The adult patient had a bony
      segment excised along with a vascularised cartilage flap for lining the glenoid.
      The child was managed with an interposition graft of costochondral cartilage
      following the release of the ankylosis, in addition to the vascularised cartilage
      flap for lining the glenoid. RESULTS: The postoperative mouth opening was good in
      both the cases with significant reduction in pain. However, the long-term results
      of this procedure are yet to be ascertained. CONCLUSIONS: The vascularised
      cartilage flap as an additional interposition material in temporomandibular joint
      surgery enables early and painless mouth-opening with good short-term results.
      The potential applicability of this flap in various pathologies of the
      temporomandibular joint is enormous.

PMID- 19753249
TI  - "Oriental anthropometry" in plastic surgery.
AB  - BACKGROUND: According to Chinese medicine, the acupuncture-points' (acupoints)
      locations are proportionally and symmetrically distributed in well-defined
      compartment zones on the human body surface Oriental Anthropometry" (OA).
      Acupoints, if considered as aesthetic-loci, might be useful as reference guides
      in plastic surgery (PS). AIM: This study aimed to use aesthetic-loci as
      anatomical reference in surgical marking of Aesthetic Plastic Surgery. METHOD:
      This was an observational study based on aesthetic surgeries performed in private
      clinic. This study was based on 106 cases, comprising of 102 women and 4 men,
      with ages varying from 07 to 73 years, and with heights of between 1.34 m and
      1.80 m. Patients were submitted to aesthetic surgical planning by relating
      aesthetic-loci to conventional surgical marking, including breast surgeries,
      abdominoplasty, rhytidoplasty, blepharoplasty, and hair implant. The aesthetic
      surgical-outcome (ASO) of the patients was assessed by a team of plastic surgeons
      (who were not involved in the surgical procedures) over a follow-up period of one
      year by using a numeric-rating-scale in percentage (%) terms. A four-point-verbal
      rating-scale was used to record the patients' opinion of therapeutic-satisfaction
      (TS). RESULTS: ASO was 75.3 +/- 9.4% and TS indicated that most patients (58.5%)
      obtained "good" results. Of the remainder, 38.7% found the results "excellent",
      and 2.8% found them "fair". DISCUSSION AND CONCLUSION: The data suggested that
      the use of aesthetic-loci may be a useful tool for PS as an anatomical reference
      for surgical marking. However, further investigation is required to assess the
      efficacy of the OA by providing the patients more reliable balance and harmony in
      facial and body contours surgeries.

PMID- 19753250
TI  - Project Muskan: Social responsibility of the plastic surgeon.
AB  - Although exact statistics are not available, Indian plastic surgeons see around
      7,00,000-8,00,000 burn admissions annually with around 10,00,000 cleft patients
      yet to be operated. In spite of this voluminous load, India does not have
      national health programs for the various deformities Indian plastic surgeons
      typically treat. As Plastic Surgeons, it is our social responsibility to treat
      these patients and bring 'muskan' (smile in Hindi) back into their lives. Project
      Muskan was initiated as an innovative model for targeting these patients and is
      probably one of its kind in the field of plastic surgery in our country. It is
      unique because it is a perfect collaboration of government institutions, a Non
      Government Organization (NGO), and cooperative sectors providing free health care
      at the doorstep. Identification of the patients was done with the help of the
      extensive milk dairy network in the state of Gujarat. Provision of transport and
      other facilities was done by the NGOs and quality health care provision was taken
      care of by the government hospital. Project Muskan started from a single village
      but now covers around 3000 villages and tribal areas of Gujarat. It is a system
      that can be easily reproducible in all hospitals and has reestablished the faith
      of the common man in government institutes.

PMID- 19753251
TI  - Is it safe to combine abdominoplasty and posterior vaginal repair in one surgical
      session?
AB  - Many multiparous women complain of protruded and pendulous abdomens and vaginal
      outlet relaxation which affect their sexual relationships with their male
      partners. This study included 47 patients who had these complaints. Some of these
      patients were working outside the homes and all were mothers of 2-5 children. Due
      of their home and job responsibilities, they did not have enough time or money
      for multiple surgeries in more than one session. MATERIAL AND METHODS: The age of
      these patients was 26-54 years and all patients had poor skin elasticity,
      pendulous excess subcutaneous fat and skin below the level of the anterior vulvar
      commissure, and a lax musculoaponeurotic anterior abdominal wall. Also, all
      patients had a relaxed vaginal outlet and 32 patients had rectocele. Careful
      perioperative assessment and management was done for each patient to ensure
      fitness for the long operation and to avoid complications. The combined surgical
      session consisted of two steps: abdominoplasty and posterior vaginal repair. All
      the patients were kept in the hospital for two days and they returned to their
      usual routines in the third week after surgery, and they resumed their sexual
      relationships with their male partners in the sixth week after surgery. RESULTS:
      There were no serious complications and this approach was convenient for the
      patients and their families. The recovery time of the combined surgical session
      was the same as that of just abdominoplasty, and significantly less than the sum
      of the recovery periods if the two surgeries had been performed in two sessions.
      The cost of the combined surgical session was significantly less than doing the
      surgeries in two sessions. All the patients had significant improvement in their
      sexual relationships.

PMID- 19753252
TI  - The association between blood groups and maxillofacial deformities.
AB  - BACKGROUND: Blood group is a genetic characteristic which is associated with some
      diseases and deformities. Multifactorial characteristics of facial development
      make it difficult to predict a genetic pattern in a specific maxillofacial
      deformity, but epidemiological evaluations can reveal relationships between such
      deformities and some genetic characteristics or accompanied diseases, and this
      will help to recognise and treat them. The aim of this study is evaluation of the
      relationship between blood groups and maxillofacial deformities. MATERIALS AND
      METHODS: In this study, blood groups of 190 patients with maxillofacial
      deformities who had had orthognathic surgery in Alzahra hospital, Isfahan, were
      compared with the general Iranian population. RESULTS: Among 190 patients, 93
      cases (49%) were men and 97 cases (51%) were women. Fifteen cases (8%) were < 20
      years old, 130 cases (68%) were 20-30 years old, and the others (45 cases, 24%)
      were > 30 years old. The blood group distribution in our samples was as follows:
      blood group O = 76 cases (40%), blood group A = 58 cases (30%), blood group B =
      41 cases (22%), and blood group AB = 15 cases (8%). Among these patients, 31
      cases (16%) had maxillary deformities and 27 cases (14%) suffered from mandibular
      deformities while the other 132 cases (70%) had bimaxillary problems. The Chi
      square test showed statistically significant differences between the blood group
      distribution of the patients of this study and the normal Iranian population (P <
      0.001). CONCLUSION: It was shown that among different blood groups; those with
      blood group B have a greater likelihood of association with maxillofacial
      deformities. On the other hand, the probability of the association of such
      deformities was the least with blood group A.

PMID- 19753253
TI  - Endoscopic resection of forehead lipoma: A subperiosteal single-portal approach.
AB  - Forehead lumps which are commonly excised for cosmetic reasons, are done through
      a traditional open excision technique. In the Asian population, open excision
      commonly results in a pigmented scar which tends not to fade with time and this
      can be a concern to some patients. The aims of this paper are to describe an
      endoscopically assisted technique of surgery, with emphasis on the subperiosteal,
      single-portal approach; to review the outcome of the surgery, and to define the
      indications for its use. MATERIALS AND METHODS: We describe here a case series of
      ten patients, in whom a minimally invasive technique was employed for the removal
      of a forehead lipoma via an endoscopic, single-portal, subperiosteal approach.
      RESULTS: The patients' age ranged from 26 to 54 years and the dimensions of the
      masses removed ranged from 1.0 x 0.5 cm to 3.0 x 3.0 cm. All were confirmed by
      histological examination to be lipomata. The patients were followed up for an
      average period of nine months. There were no residual masses or recurrences and
      no complications of nerve damage. All the patients were very satisfied with their
      'scar less' operations. CONCLUSIONS: Endoscopic excision of forehead lipomas
      through a single-port approach is both safe and reliable. It is indicated in
      patients who are prone to scarring or who are concerned with a forehead scar.

PMID- 19753254
TI  - Extravasational side effects of cytotoxic drugs: A preventable catastrophe.
AB  - In addition to their therapeutic effects on malignant cells, cytotoxic agents
      have the potential of causing destruction of healthy, normal cells. Extravasation
      of the drug can produce extensive necrosis of the skin and subcutaneous tissue.
      Management of these extravasational effects differs from one centre to another
      and prevention is usually strongly emphasized. We analyzed our management of 12
      patients referred to us over five years with extravasation of cytotoxic drugs and
      reviewed the literature for different approaches with regard to prophylaxis and
      management of extravasational effects. MATERIALS AND METHODS: This study was done
      in the department of plastic surgery of a medical college. Five years of
      retrospective data were studied of patients referred to our department with
      extravasation of cytotoxic drugs. RESULTS: We managed 12 cases referred to our
      department with extravasation of cytotoxic drugs. Mitomycin C was used in seven
      cases (58.33%), vincristine in two cases (16.66%), 5-Florouracil in another two
      cases while doxorubicin was responsible for extravasational side effects in one
      case (8.33%). The size of necrosis ranged from 3.75 cm(2) to 25 cm(2) with
      average size of 9.6 cm(2). In terms of the area involved, the dorsum of the hand
      was involved in five cases (41.66%), the wrist in another five cases (41.66%),
      and the cubital fossa in the remaining two cases (16.66%). All cases were treated
      with daily debridement of necrotic tissue, saline dressing, and split skin
      grafting. CONCLUSION: Extravasation of cytotoxic drugs further increases the
      suffering of cancer patients. This catastrophe can only be avoided by vigilance
      and immediate application of antidotes. Once the local toxicity of the drugs
      takes effect, morbidity is unavoidable.

PMID- 19753255
TI  - Maxillonasal dysplasia (Binder's syndrome) and its treatment with costal
      cartilage graft: A follow-up study.
AB  - Maxillonasal dysplasia or Binder's syndrome is an uncommon congenital condition
      characterized by a retruded mid-face with an extremely flat nose. We report here
      six patients with maxillonasal dysplasia whose noses were corrected with onlay
      costal cartilage grafts using a combined oral vestibular and external rhinoplasty
      approach for nasal dorsal augmentation, columellar lengthening, and premaxillary
      augmentation. The cartilage graft was dipped in a solution of 100 ml 0.9% NaCl
      and one vial (80mg) gentamicin for 30 min to prevent warping. L struts made for
      nasal augmentation, columellar lengthening, and premaxillary augmentation were
      fixed to one another by slots made in the graft. This technique has been used in
      children, adults, and for secondary cases with promising results. All patients
      were of class I dental occlusion. The nasal and premaxillary augmentation which
      was monitored by serial photography was found to be stable over a follow-up
      period of three years.

PMID- 19753256
TI  - Maxillonasal dysplasia (Binder's syndrome) and its treatment with costal
      cartilage graft: A follow-up study.

PMID- 19753257
TI  - Irrigation-coupled bipolar cautery unit: A practical, economical, and simple
      version.
AB  - Hemostasis is a fundamental principle of surgery for which electrocoagulation is
      universally used. Bipolar electrocautery has an advantage over monopolar
      electrocautery in terms of the precision of the extent of tissue coagulation and
      the lateral extent of thermal tissue injury. However, secondary to the thermal
      changes induced in the tissue due to electric current passage, there is charring
      of tissue, which adheres to the cautery tip. This, not only decreases its
      effectiveness, but also, by getting avulsed while removing the cautery tip from
      the surgical field, causes rebleeding and more trauma to the tissue. Irrigation
      of the surgical field during application of cautery reduces the charring effect,
      thereby improving the efficiency and efficacy. Irrigation-coupled electrocautery
      devices are available but are costly to acquire and maintain. We describe a
      simple and reliable version of an irrigation-coupled cautery device, which is of
      immense functional utility in our experience. It decreases the amount of charring
      of the tissue and its adherence to the bipolar forceps tips, thereby decreasing
      the frustrating loss of effectiveness and also increases the life of the bipolar
      forceps as cleaning needs to be less frequent. By virtue of its simplicity and
      cost-effectiveness, it can be used in almost all hospitals and situations.

PMID- 19753258
TI  - Notch-free vermillion after unilateral cleft lip repair: The Charles Pinto centre
      protocol.
AB  - A notch on the vermillion is one of the most common complications following the
      repair of a unilateral cleft lip. Several methods have been described for the
      secondary correction of a notch. However, there are only a few reports on how the
      notch can be prevented during primary lip repair. Causes of a vermillion notch
      were analysed at the Charles Pinto Centre for Cleft Lip and Palate and each
      possible cause addressed by an appropriate procedure. This protocol was then
      followed in every patient. In this manner, we have been able to avoid notches in
      unilateral cleft lips altogether and more significantly, junior trainees in our
      department have also been able to consistently avoid a notch in their repairs.

PMID- 19753259
TI  - The Naso-labial and lateral forehead flaps as a single stage: A case report and
      review of literature.
AB  - We present here the case of a patient with a major traumatic nasal loses who had
      a near-total nasal reconstruction as a single-stage procedure. A 35 year-old
      civil servant who was involved in a road traffic injury about two years before
      presentation. He sustained extensive and multiple facial injuries with complete
      loss of nasal cover and lining. Reconstruction was performed by using superiorly
      based, bilateral, nasolabial flaps to line the floor and the nasal septum, and a
      paramedian forehead flap for skin cover. The patient did well postoperatively and
      was discharged home on the 7(th) postoperative day. If the principles concerning
      cover, support, and lining are adhered to, excellent functional and aesthetic
      results can be achieved as we have obtained in our patient.

PMID- 19753260
TI  - Surgery of temporomandibular joint under local anaesthesia.
AB  - Temporomandibular joint ankylosis is a debilitating disorder arising from an
      inability to open the mouth. This leads to poor nutrition, poor dental hygiene,
      and stunted growth. Anaesthesia, especially general anaesthesia, is very
      difficult to administer. There is a lack of direct visualization of the vocal
      cords, tongue fall following relaxation, and an already narrowed passage due to a
      small mandible, which makes even the blind nasal intubation difficult. There are
      various techniques described in literature to overcome these challenges, failing
      which, one needs to do tracheostomy. All the risks of difficult intubation and
      general anaesthesia can be avoided if the surgery is done under local
      anaesthesia. A simple but effective method of successful local anaesthesia is
      described, which allows successful temporomandibular joint reconstruction.

PMID- 19753261
TI  - Management strategy for facial arteriovenous malformations.
AB  - Arteriovenous malformations (AVMs) are uncommon errors of vascular morphogenesis;
      haemodynamically, they are high-flow lesions. Approximately 50% of AVMs are
      located in the craniofacial region. Subtotal excision or proximal ligation of the
      feeding vessel frequently results in rapid progression of the AVMs. Hence, the
      correct treatment consists of highly selective embolisation (super-selective)
      followed by complete resection 24-48 hours later. We treated 20 patients with
      facial arteriovenous malformation by using this method. Most of the lesions (80%)
      were located within the cheek and lip. There were no procedure related
      complications and cosmetic results were excellent.

PMID- 19753262
TI  - Perineal burn contractures: An experience in tertiary hospital of a Himalayan
      State.
AB  - Perineal burn contracture is a rare burn sequel. We conducted a retrospective
      analysis of cases with perineal burn contractures managed in a tertiary care
      centre of a Himalayan state. We found that all cases sustained burn injury from
      burning firewood and the time of presentation was two to six years after the burn
      injury. We analyzed our treatment method and have classified these contractures
      into two types.

PMID- 19753263
TI  - Complete cleft of the upper limb: A very rare anomaly.
AB  - BACKGROUND: We describe here a very rare congenital deformity that involves the
      splitting of the right upper limb with the superior limb articulating with the
      shoulder joint, and the inferior limb laterally attached to the chest wall.
      MATERIAL AND METHODS: The child with this rare split limb was treated by
      transferring the inferior limb on an islanded pedicle to the superior one while
      creating the hand. RESULTS: A unified limb was reconstructed while creating the
      hand without any compromise on the existing function and vascularity. The patient
      is on regular follow-up and further staged procedures have been planned to
      provide a better functional and aesthetic limb. CONCLUSION: The congenital
      deformity described here has not been mentioned in world literature so far and
      its embryological basis is a matter of discussion. Opinions regarding further
      management of this anomaly are invited from experts in the field.

PMID- 19753264
TI  - Complete cleft of the upper limb: A very rare anomaly.

PMID- 19753265
TI  - Adenoid cystic carcinoma of the parotid gland: Anastamosis of the facial nerve
      with the great auricular nerve after radical parotidectomy.
AB  - Adenoid cystic carcinoma of the parotid gland is a rare and slowly growing, but
      highly malignant tumor. Surgical resection of a malignant parotid tumor should
      include resection of the facial nerve when the nerve is involved in the tumor.
      Facial nerve reconstruction is required after nerve resection. A 14 year-old
      female presented with complaints of painless enlargement of the right parotid
      gland and facial asymmetry. Physical examination revealed a firm mass in the
      region of the parotid gland as well as right facial paralysis. Biopsy obtained
      from the mass showed an adenoid cystic carcinoma of the parotid gland. A radical
      parotidectomy with a modified radical neck dissection was carried out. Grafting
      material for the facial reconstruction was harvested from the great auricular
      nerve. The proximal main trunk and each distal branch of the facial nerve were
      coapted with the greater auricular nerve. The patient received radiotherapy after
      surgery and was seen to achieve grade IV facial function one year after surgery.
      Thus, the great auricular nerve is appropriate grafting material for coaptation
      of each distal branch of the facial nerve.

PMID- 19753266
TI  - Microneurovascular reimplantation in a case of total penile amputation.
AB  - Amputation of the penis is a rare condition reported from various parts of the
      world as isolated cases or small series of patients; the common aetiology is self
      mutilating sharp amputation or an avulsion or crush injury in an industrial
      accident. A complete reconstruction of all penile structures should be attempted
      in one stage which provides the best chance for full rehabilitation of the
      patient. We report here a single case of total amputation of the penis, which was
      successfully reattached by using a microsurgical technique. After surgery, near
      normal appearance and function including a good urine flow and absence of
      urethral stricture, capabilities of erection and near normal sensitivity were
      observed.

PMID- 19753267
TI  - Twenty years' follow-up of a de-epithelialised turnover flap.
AB  - The authors have used the de-epithelialised turnover flap (Thatte's Flap) for
      covering compound defects over the tendo-achilles in 31 patients in the period
      covering 1980-2000. Two of these patients have come up for follow-up after 20
      years. In this late follow-up, the results are good and the tendon which was
      bridged by the dermis of the flap is functioning to allow the patients to stand
      on their toes. The de-epithelialised turnover flap is a simple and easy technique
      giving good long-term results. In spite of all the new advances in flap coverage,
      the de-epithelialised turnover flap is a good alternative for the tendo-achilles
      area in the armamentarium of a plastic surgeon.

PMID- 19753268
TI  - Intravenous injection of elemental mercury: A report of two cases.
AB  - Two cases of intravenous injection of elemental mercury are described in this
      report. One patient succumbed and the other remains asymptomatic two years after
      the surgical removal of all the injected mercury. Management of intravenous
      injection of elemental mercury (intended to be an aphrodisiac in these two cases)
      is discussed here and the need for surgical removal of all accessible mercury has
      been emphasized.

PMID- 19753269
TI  - Superficial thrombophlebitis (Mondor's Disease) after breast augmentation
      surgery.
AB  - Although the aetiology of Mondor's disease remains unclear, the most commonly
      cited cause is trauma of some sort. Although surgical trauma has frequently been
      quoted, reports that specifically implicate aesthetic breast surgery are unusual
      in the literature. In this article, the authors report a case of superficial
      thrombophlebitis of the anterolateral chest wall secondary to breast augmentation
      surgery in a woman, five months after the procedure. The authors performed an
      analysis of the disease's main etiologic components and preponderant clinical
      aspects, and determined all appropriate therapeutic measures.

PMID- 19753270
TI  - Roberts-SC syndrome, a rare syndrome and cleft palate repair.
AB  - Roberts SC syndrome is a rare syndrome with only 17 previously recognized
      patients reported in medical literature. The syndrome is characterized by
      multiple malformations, particularly, symmetrical limb reduction, craniofacial
      anomalies such as bilateral cleft lip and palate, micrognathia, and severe growth
      and mental retardation. Our patient, a young child of five years having Roberts
      SC, was successfully operated for cleft palate under general anesthesia. The main
      features of the syndrome and the technical problems of anesthesia and surgery are
      discussed in this report.

PMID- 19753271
TI  - Double breasting repair of urethral fistula in a patient with perineal abscess
      secondary to a large urethral stone.
AB  - We report here a case of urethral fistula managed successfully following incision
      and drainage for the urethral abscess secondary to a large urethral stone leading
      to a large diverticulum (another rare condition) by using the technique of double
      breasting, where we used the redundant urethra and overlying skin.

PMID- 19753272
TI  - Adnexal carcinomas of the head and neck.
AB  - Adnexal carcinomas of the skin are rare and they derive from structures such as
      sweat glands, sebaceous glands, and hair follicles. Adnexal tumors represent 1-2%
      of skin cancers. Between 1998 and 2004, eight patients with malignant adnexal
      tumors of the head and neck were treated in the Plastic Surgery Service in
      Argerich Hospital in Buenos Aires, Argentina. Four (50%) of them had malignant
      cylindromas, two (25%) had sebaceous carcinoma, and the other two (25%) syringoid
      eccrine carcinoma. Tumor resection and local flaps were made in all cases. In one
      case, a radical neck dissection with superficial parotidectomy was performed to
      treat the metastatic cervical nodes. Local recurrence observed in two cases (25%)
      was associated with distant metastasis and death of the patients. In other six
      cases, the survival rate was 75% after five years.

PMID- 19753274
TI  - A simple method to make a reusable volar splint.

PMID- 19753273
TI  - A simple and cost-effective protocol for the management of anterolateral thigh
      free-flap donor site.

PMID- 19753275
TI  - Lipoma of the finger presenting as restricted motion.

PMID- 19753276
TI  - Congenital dermoid cysts of the anterior fontanel.

PMID- 19753277
TI  - Compartment syndrome: A rare complication of tensor fascia lata flap
      reconstruction following ilio-inguinal block dissection.

PMID- 19753280
TI  - The looming environmental crisis.

PMID- 19753281
TI  - Study of prescription of injectable drugs and intravenous fluids to inpatients in
      a teaching hospital in Western Nepal.
AB  - Unnecessary, excessive and poor injection practices in the South East Asia region
      (including Nepal) have been observed previously. The authors aim to study
      prescription of injectable drugs to inpatients in a teaching hospital in Western
      Nepal. Prescription of injectable drugs (IDs) and intravenous fluids (IVFs) to
      inpatients discharged from the wards of the Manipal Teaching Hospital during 1st
      January to 30th June 2006 was studied. The mean number of drugs, IDs and IVFs
      administered, median cost of drugs and of IDs/IVFs per prescription calculated.
      Comparison of ID/IVF use in the four major hospital departments (Medicine,
      Obstetrics and Gynecology, Pediatrics and Surgery) was done. The administration
      of IDs/IVFs and injectable antimicrobials were measured in Defined Daily Dose
      (DDD)/100 bed-days and of Intravenous fluid in Liters (L)/100 bed-days. Of the
      1131 patients discharged, 938 (82.94%) patients received one or more IDs/IVFs.
      The mean number of drugs, IDs and IVFs prescribed were 8.75, 4.72 and 1.42.
      Median cost of drugs and IDs/IVFs per prescription were 8.26US$ and 5.12US$
      respectively. IDs/IVFs accounted for 81.37% of total drug cost. The most commonly
      used ID, injectable antimicrobial and IVF were Diclofenac (19.3 DDD/100 bed
      days), Metronidazole (7.68 DDD/100 bed-days) and Dextrose normal saline (8.56
      L/100 bed-days), respectively. The total IVF consumption was 24.25 L/100 bed
      days. Significant differences between departments were observed (p<0.05). In
      conclusion, the use of IDs/IVFs was higher compared to other studies.
      Interventions to improve IDs/IVFs prescribing practices may be required.

PMID- 19753282
TI  - Total revision of the hip using allograft to correct particle disease induced
      osteolysis: a case study.
AB  - Total hip replacement is considered to be a highly successful and routine
      surgery; however, the internal components produce particles through friction and
      wear in the device. These particles are identified as one of the main reasons for
      total hip revisions. The generated, biologically active, particles provoke the
      formation of osteolytic areas through the inhibition of bone formation and
      increased fluid production. The resulting bone loss can be managed through the
      use of allograft bone in combination with bone chips and cement. In addition,
      implants constructed with highly porous trabecular metal can be used to further
      facilitate rapid and extensive tissue infiltration resulting in strong implant
      attachment. In this case study we show the use of a tibial allograft coupled with
      bone chips and cement to cover and support a lytic cyst in the proximal femur,
      distal to the greater trochanter. Additionally, we detail the use of a trabecular
      metal cup to halt the migration of the component into the acetabulum and promote
      greater fixation and bone ingrowth.

PMID- 19753283
TI  - Morgagni hernia: ten years of idiopathic vomiting.

PMID- 19753284
TI  - Jejunal intussusception as an unusual cause of abdominal pain in an adult.

PMID- 19753285
TI  - An unidentified monster in the bed--assessing nocturnal asthma in children.
AB  - Nocturnal asthma (NA) is increasing in prevalence, affecting millions of people
      worldwide. In addition to being associated with increased mortality, NA is
      associated with a decreased quality of life. NA associated sleep disturbances and
      increased daytime sleepiness are especially important in children due to the
      accompanying behavioral and developmental difficulties. As diurnal spirometry is
      not a practical tool for the diagnosis and monitoring of NA, self or parental
      reports are used. Children underreport and underestimate their NA symptoms and
      parents are not fully aware of their child's NA indicators. In addition, there is
      the lack of physician familiarity regarding the assessment and treatment of NA.
      Therefore, NA is chronically underreported. The development of a non-invasive,
      objective, home-based diagnostic tool is crucial in diagnosing and monitoring
      children with NA. The presence of wheeze during sleep has been successfully
      employed as a tool to measure NA in children. This review discusses the
      increasing prevalence of NA, current diagnostic tools and the consequences of
      undiagnosed NA in children. In conclusion, this paper suggests that an automated
      wheeze detective device is an objective and practical tool to aid the diagnosis
      and monitoring of NA.

PMID- 19753287
TI  - Aftershock medicine: a Canadian returns to China following the 2008 Sichuan
      earthquake.

PMID- 19753286
TI  - Suppressive valacyclovir therapy to reduce genital herpes transmission: good
      public health policy?
AB  - Nocturnal asthma (NA) is increasing in prevalence, affecting millions of people
      Genital herpes is a widespread sexually transmitted infection caused by the
      herpes simplex viruses (HSV). Suppressive valacyclovir therapy has been shown to
      significantly reduce HSV transmission. The benefits and costs of using
      valacyclovir to reduce transmission in couples discordant for genital herpes will
      be analyzed in order to better inform decision-making. By reducing transmission,
      the physical and psychological harms of living with symptomatic genital herpes
      will be prevented while saving on certain healthcare costs. However, the large
      number needed to treat and the low symptomatic rate among infected individuals
      may outweigh these benefits. The costs of trying to achieve a significant
      reduction in incidence include the psychological harms of identifying
      asymptomatic individuals through a large screening program and the economic costs
      of the antiviral agent and screening. When these issues are weighed, the high
      economic costs render a program to reduce incidence unfeasible. Nevertheless, it
      is clinically important to consider the consequences of transmission at an
      individual level. The specific circumstances that influence the decision to use
      suppressive therapy are identified.

PMID- 19753288
TI  - Evidence based medicine in cultural and historical context.

PMID- 19753289
TI  - Medical leadership: doctors at the helm of change.

PMID- 19753290
TI  - The effects of outdoor air pollution on chronic illnesses.

PMID- 19753291
TI  - Beyond the news: health risks of climate change.

PMID- 19753292
TI  - Psychiatry as a career: a survey of factors affecting students' interest in
      psychiatry as a career.
AB  - The objectives of this study were to determine the characteristics of medical
      students and graduates interested in choosing psychiatry as a career and the
      obstacles in choosing this field of medicine. Two private and two public medical
      institutes were surveyed from June 2007 to August 2007. A self-administered
      questionnaire was distributed to third, fourth and final year students and to
      medical graduates doing their internship in these four medical institutes. A
      total of 909 medical students and graduates participated in the study. Seventeen
      percent of participants responded positively regarding their interest in
      psychiatry as a career. Significantly higher proportion belonged to private
      medical institutes (14% vs. 24%, P-value =0.001). There was no significant
      difference in reporting interest for psychiatry in regard to age, sex, year in
      medical school and whether or not the participant had done a psychiatry ward
      rotation. However significantly higher proportion of participants (22%, n=43)
      were reporting their interest in the field of psychiatry who had done more than a
      month long psychiatry ward rotation as compared to those participants (14%, n=54)
      with less than a month or no psychiatry rotation (P-value=0.01). More students
      were reporting their interest in psychiatry with a family history of psychiatric
      illness as compared to without family history (24% vs 16%, P-value=0.03). In
      conclusion, students and graduates with more than a month long rotation in
      psychiatry, studying in private medical colleges and with a family history of
      psychiatric illness were more interested in choosing psychiatry as a career.

PMID- 19753293
TI  - Does exposure to agricultural chemicals increase the risk of prostate cancer
      among farmers?
AB  - Several studies suggest that farmers may be at increased risk of prostate cancer.
      The present analysis, based on a large population-based case-control study
      conducted among men in the Montreal area in the early 1980's, aim at identifying
      occupational chemicals which may be responsible for such increases. The original
      study enrolled 449 prostate cancer cases, nearly 4,000 patients with other
      cancers, as well as 533 population controls. Subjects were interviewed about
      their occupation histories, and a team of industrial hygienists assigned their
      past exposures using a checklist of some 300 chemicals. The present analysis was
      restricted to a study base of men who had worked as farmers earlier in their
      lives. There were a total of 49 men with prostate cancers, 127 with other cancers
      and 56 population controls. We created a pool of 183 controls combining the
      patients with cancers at sites other than the prostate and the population
      controls. We then estimated the odds ratio for prostate cancer associated with
      exposure to each of 10 agricultural chemicals, i.e., pesticides, arsenic
      compounds, acetic acid, gasoline engine emissions, diesel engine emissions,
      polycyclic aromatic hydrocarbons from petroleum, lubricating oils and greases,
      alkanes with >or=18 carbons, solvents, and mononuclear aromatic hydrocarbons.
      Based on a model adjusting for age, ethnicity, education, and respondent status,
      there was evidence of a two-fold excess risk of prostate cancer among farmers
      with substantial exposure to pesticides [odds ratio (OR)=2.3, 95% confidence
      interval (CI) 1.1-5.1], as compared to unexposed farmers. There was some
      suggestion, based on few subjects, of increased risks among farmers ever exposed
      to diesel engine emissions (OR=5.7, 95% CI 1.2-26.5). The results for pesticides
      are particularly noteworthy in the light of findings from previous studies.
      Suggestions of trends for elevated risks were noted with other agricultural
      chemicals, but these are largely novel and need further confirmation in larger
      samples.

PMID- 19753294
TI  - Climate change and health in Canada.

PMID- 19753296
TI  - Read any good books lately?

PMID- 19753295
TI  - Food, global environmental change and health: EcoHealth to the rescue?

PMID- 19753297
TI  - A McGill update of Osler's Bedside Books List.

PMID- 19753298
TI  - MicroRNA profiling and head and neck cancer.
AB  - Head and neck/oral cancer (HNOC) is a devastating disease. Despite advances in
      diagnosis and treatment, mortality rates have not improved significantly over the
      past three decades. Improvement in patient survival requires a better
      understanding of the disease progression so that HNOC can be detected early in
      the disease process and targeted therapeutic interventions can be deployed.
      Accumulating evidence suggests that microRNAs play important roles in many human
      cancers. They are pivotal regulators of diverse cellular processes including
      proliferation, differentiation, apoptosis, survival, motility, and morphogenesis.
      MicroRNA expression patterns may become powerful biomarkers for diagnosis and
      prognosis of HNOC. In addition, microRNA therapy could be a novel strategy for
      HNOC prevention and therapeutics. Recent advances in microRNA expression
      profiling have led to a better understanding of the cancer pathogenesis. In this
      review, we will survey recent technological advances in microRNA profiling and
      their applications in defining microRNA markers/targets for cancer prediction,
      diagnostics, treatment, and prognostics. MicroRNA alterations that consistently
      identified in HNOC will be discussed, such as upregulation of miR-21, miR-31, miR
      155, and downregulation of miR-26b, miR-107, miR-133b, miR-138, and miR-139.

PMID- 19753299
TI  - Information infrastructure for cooperative research in neuroscience.
AB  - The paper describes a framework for efficient sharing of knowledge between
      research groups, which have been working for several years without flaws. The
      obstacles in cooperation are connected primarily with the lack of platforms for
      effective exchange of experimental data, models, and algorithms. The solution to
      these problems is proposed by construction of the platform (EEG.pl) with the
      semantic aware search scheme between portals. The above approach implanted in the
      international cooperative projects like NEUROMATH may bring the significant
      progress in designing efficient methods for neuroscience research.

PMID- 19753300
TI  - Immunomodulation with recombinant interferon-gamma1b in pulmonary tuberculosis.
AB  - BACKGROUND: Current treatment regimens for pulmonary tuberculosis require at
      least 6 months of therapy. Immune adjuvant therapy with recombinant interferon
      gamma1b (rIFN-gammab) may reduce pulmonary inflammation and reduce the period of
      infectivity by promoting earlier sputum clearance. METHODOLOGY/PRINCIPAL
      FINDINGS: We performed a randomized, controlled clinical trial of directly
      observed therapy (DOTS) versus DOTS supplemented with nebulized or subcutaneously
      administered rIFN-gamma1b over 4 months to 89 patients with cavitary pulmonary
      tuberculosis. Bronchoalveolar lavage (BAL) and blood were sampled at 0 and 4
      months. There was a significant decline in levels of inflammatory cytokines IL
      1beta, IL-6, IL-8, and IL-10 in 24-hour BAL supernatants only in the nebulized
      rIFN-gamma1b group from baseline to week 16. Both rIFN-gamma1b groups showed
      significant 3-fold increases in CD4+ lymphocyte response to PPD at 4 weeks. There
      was a significant (p = 0.03) difference in the rate of clearance of Mtb from the
      sputum smear at 4 weeks for the nebulized rIFN-gamma1b adjuvant group compared to
      DOTS or DOTS with subcutaneous rIFN-gamma1b. In addition, there was significant
      reduction in the prevalence of fever, wheeze, and night sweats at 4 weeks among
      patients receiving rFN-gamma1b versus DOTS alone. CONCLUSION: Recombinant
      interferon-gamma1b adjuvant therapy plus DOTS in cavitary pulmonary tuberculosis
      can reduce inflammatory cytokines at the site of disease, improve clearance of
      Mtb from the sputum, and improve constitutional symptoms. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT00201123.

PMID- 19753301
TI  - Inhibitors of MyD88-dependent proinflammatory cytokine production identified
      utilizing a novel RNA interference screening approach.
AB  - BACKGROUND: The events required to initiate host defenses against invading
      pathogens involve complex signaling cascades comprised of numerous adaptor
      molecules, kinases, and transcriptional elements, ultimately leading to the
      production of proinflammatory cytokines, such as tumor necrosis factor alpha (TNF
      alpha). How these signaling cascades are regulated, and the proteins and
      regulatory elements participating are still poorly understood. RESULTS: We report
      here the development a completely random short-hairpin RNA (shRNA) library
      coupled with a novel forward genetic screening strategy to identify inhibitors of
      Toll-like receptor (TLR) dependent proinflammatory responses. We developed a
      murine macrophage reporter cell line stably transfected with a construct
      expressing diphtheria toxin-A (DT-A) under the control of the TNF-alpha-promoter.
      Stimulation of the reporter cell line with the TLR ligand lipopolysaccharide
      (LPS) resulted in DT-A induced cell death, which could be prevented by the
      addition of an shRNA targeting the TLR adaptor molecule MyD88. Utilizing this
      cell line, we screened a completely random lentiviral short hairpin RNA (shRNA)
      library for sequences that inhibited TLR-mediated TNF-alpha production. Recovery
      of shRNA sequences from surviving cells led to the identification of unique shRNA
      sequences that significantly inhibited TLR4-dependent TNF-alpha gene expression.
      Furthermore, these shRNA sequences specifically blocked TLR2 but not TLR3
      dependent TNF-alpha production. CONCLUSIONS: Thus, we describe the generation of
      novel tools to facilitate large-scale forward genetic screens in mammalian cells
      and the identification of potent shRNA inhibitors of TLR2 and TLR4- dependent
      proinflammatory responses.

PMID- 19753302
TI  - Global gene expression profiling of human pleural mesotheliomas: identification
      of matrix metalloproteinase 14 (MMP-14) as potential tumour target.
AB  - BACKGROUND: The goal of our study was to molecularly dissect mesothelioma tumour
      pathways by mean of microarray technologies in order to identify new tumour
      biomarkers that could be used as early diagnostic markers and possibly as
      specific molecular therapeutic targets. METHODOLOGY: We performed Affymetrix
      HGU133A plus 2.0 microarray analysis, containing probes for about 39,000 human
      transcripts, comparing 9 human pleural mesotheliomas with 4 normal pleural
      specimens. Stringent statistical feature selection detected a set of
      differentially expressed genes that have been further evaluated to identify
      potential biomarkers to be used in early diagnostics. Selected genes were
      confirmed by RT-PCR. As reported by other mesothelioma profiling studies, most of
      genes are involved in G2/M transition. Our list contains several genes previously
      described as prognostic classifier. Furthermore, we found novel genes, never
      associated before to mesotheliom that could be involved in tumour progression.
      Notable is the identification of MMP-14, a member of matrix metalloproteinase
      family. In a cohort of 70 mesothelioma patients, we found by a multivariate Cox
      regression analysis, that the only parameter influencing overall survival was
      expression of MMP14. The calculated relative risk of death in MM patients with
      low MMP14 expression was significantly lower than patients with high MMp14
      expression (P = 0.002). CONCLUSIONS: Based on the results provided, this molecule
      could be viewed as a new and effective therapeutic target to test for the cure of
      mesothelioma.

PMID- 19753303
TI  - A discrete time model for the analysis of medium-throughput C. elegans growth
      data.
AB  - BACKGROUND: As part of a program to predict the toxicity of environmental agents
      on human health using alternative methods, several in vivo high- and medium
      throughput assays are being developed that use C. elegans as a model organism. C.
      elegans-based toxicological assays utilize the COPAS Biosort flow sorting system
      that can rapidly measure size, extinction (EXT) and time-of-flight (TOF), of
      individual nematodes. The use of this technology requires the development of
      mathematical and statistical tools to properly analyze the large volumes of
      biological data. METHODOLOGY/PRINCIPAL FINDINGS: Findings A Markov model was
      developed that predicts the growth of populations of C. elegans. The model was
      developed using observations from a 60 h growth study in which five cohorts of
      300 nematodes each were aspirated and measured every 12 h. Frequency
      distributions of log(EXT) measurements that were made when loading C. elegans L1
      larvae into 96 well plates (t = 0 h) were used by the model to predict the
      frequency distributions of the same set of nematodes when measured at 12 h
      intervals. The model prediction coincided well with the biological observations
      confirming the validity of the model. The model was also applied to log(TOF)
      measurements following an adaptation. The adaptation accounted for variability in
      TOF measurements associated with potential curling or shortening of the nematodes
      as they passed through the flow cell of the Biosort. By providing accurate
      estimates of frequencies of EXT or TOF measurements following varying growth
      periods, the model was able to estimate growth rates. Best model fits showed that
      C. elegans did not grow at a constant exponential rate. Growth was best described
      with three different rates. Microscopic observations indicated that the points
      where the growth rates changed corresponded to specific developmental events: the
      L1/L2 molt and the start of oogenesis in young adult C. elegans. CONCLUSIONS:
      Quantitative analysis of COPAS Biosort measurements of C. elegans growth has been
      hampered by the lack of a mathematical model. In addition, extraneous matter and
      the inability to assign specific measurements to specific nematodes made it
      difficult to estimate growth rates. The present model addresses these problems
      through a population-based Markov model.

PMID- 19753304
TI  - Decorin core protein (decoron) shape complements collagen fibril surface
      structure and mediates its binding.
AB  - Decorin is the archetypal small leucine rich repeat proteoglycan of the
      vertebrate extracellular matrix (ECM). With its glycosaminoglycuronan chain, it
      is responsible for stabilizing inter-fibrillar organization. Type I collagen is
      the predominant member of the fibrillar collagen family, fulfilling both
      organizational and structural roles in animal ECMs. In this study, interactions
      between decoron (the decorin core protein) and binding sites in the d and e(1)
      bands of the type I collagen fibril were investigated through molecular modeling
      of their respective X-ray diffraction structures. Previously, it was proposed
      that a model-based, highly curved concave decoron interacts with a single
      collagen molecule, which would form extensive van der Waals contacts and give
      rise to strong non-specific binding. However, the large well-ordered aggregate
      that is the collagen fibril places significant restraints on modes of ligand
      binding and necessitates multi-collagen molecular contacts. We present here a
      relatively high-resolution model of the decoron-fibril collagen complex. We find
      that the respective crystal structures complement each other well, although it is
      the monomeric form of decoron that shows the most appropriate shape
      complementarity with the fibril surface and favorable calculated energies of
      interaction. One molecule of decoron interacts with four to six collagen
      molecules, and the binding specificity relies on a large number of hydrogen bonds
      and electrostatic interactions, primarily with the collagen motifs KXGDRGE and
      AKGDRGE (d and e(1) bands). This work helps us to understand collagen-decorin
      interactions and the molecular architecture of the fibrillar ECM in health and
      disease.

PMID- 19753305
TI  - nAChRs mediate human embryonic stem cell-derived endothelial cells:
      proliferation, apoptosis, and angiogenesis.
AB  - BACKGROUND: Many patients with ischemic heart disease have cardiovascular risk
      factors such as cigarette smoking. We tested the effect of nicotine (a key
      component of cigarette smoking) on the therapeutic effects of human embryonic
      stem cell-derived endothelial cells (hESC-ECs). METHODS AND RESULTS: To induce
      endothelial cell differentiation, undifferentiated hESCs (H9 line) underwent 4
      day floating EB formation and 8-day outgrowth differentiation in EGM-2 media.
      After 12 days, CD31(+) cells (13.7+/-2.5%) were sorted by FACScan and maintained
      in EGM-2 media for further differentiation. After isolation, these hESC-ECs
      expressed endothelial specific markers such as vWF (96.3+/-1.4%), CD31 (97.2+/
      2.5%), and VE-cadherin (93.7+/-2.8%), form vascular-like channels, and
      incorporated DiI-labeled acetylated low-density lipoprotein (DiI-Ac-LDL).
      Afterward, 5x10(6) hESC-ECs treated for 24 hours with nicotine (10(-8) M) or PBS
      (as control) were injected into the hearts of mice undergoing LAD ligation
      followed by administration for two weeks of vehicle or nicotine (100 microg/ml)
      in the drinking water. Surprisingly, bioluminescence imaging (BLI) showed
      significant improvement in the survival of transplanted hESC-ECs in the nicotine
      treated group at 6 weeks. Postmortem analysis confirmed increased presence of
      small capillaries in the infarcted zones. Finally, in vitro mechanistic analysis
      suggests activation of the MAPK and Akt pathways following activation of
      nicotinic acetylcholine receptors (nAChRs). CONCLUSIONS: This study shows for the
      first time that short-term systemic administrations of low dose nicotine can
      improve the survival of transplanted hESC-ECs, and enhance their angiogenic
      effects in vivo. Furthermore, activation of nAChRs has anti-apoptotic,
      angiogenic, and proliferative effects through MAPK and Akt signaling pathways.

PMID- 19753306
TI  - Sumoylation regulates nuclear localization of lipin-1alpha in neuronal cells.
AB  - Lipin-1 is a protein that has dual functions as a phosphatidic acid
      phosphohydrolase (PAP) and a nuclear transcriptional coactivator. It remains
      unknown how the nuclear localization and coactivator functions of lipin-1 are
      regulated. Here, we show that lipin-1 (including both the alpha and beta
      isoforms) is modified by sumoylation at two consensus sumoylation sites. We are
      unable to detect sumoylation of the related proteins lipin-2 and lipin-3. Lipin-1
      is sumoylated at relatively high levels in brain, where lipin-1alpha is the
      predominant form. In cultured embryonic cortical neurons and SH-SY5Y neuronal
      cells, ectopically expressed lipin-1alpha is localized in both the nucleus and
      the cytoplasm, and the nuclear localization is abrogated by mutating the
      consensus sumyolation motifs. The sumoylation site mutant of lipin-1alpha loses
      the capacity to coactivate the transcriptional (co-) activators PGC-1alpha and
      MEF2, consistent with its nuclear exclusion. Thus, these results show that
      sumoylation facilitates the nuclear localization and transcriptional coactivator
      behavior of lipin-1alpha that we observe in cultured neuronal cells, and suggest
      that lipin-1alpha may act as a sumoylation-regulated transcriptional coactivator
      in brain.

PMID- 19753307
TI  - Oxygen consumption can regulate the growth of tumors, a new perspective on the
      Warburg effect.
AB  - BACKGROUND: The unique metabolism of tumors was described many years ago by Otto
      Warburg, who identified tumor cells with increased glycolysis and decreased
      mitochondrial activity. However, "aerobic glycolysis" generates fewer ATP per
      glucose molecule than mitochondrial oxidative phosphorylation, so in terms of
      energy production, it is unclear how increasing a less efficient process provides
      tumors with a growth advantage. METHODS/FINDINGS: We carried out a screen for
      loss of genetic elements in pancreatic tumor cells that accelerated their growth
      as tumors, and identified mitochondrial ribosomal protein L28 (MRPL28). Knockdown
      of MRPL28 in these cells decreased mitochondrial activity, and increased
      glycolysis, but paradoxically, decreased cellular growth in vitro. Following
      Warburg's observations, this mutation causes decreased mitochondrial function,
      compensatory increase in glycolysis and accelerated growth in vivo. Likewise,
      knockdown of either mitochondrial ribosomal protein L12 (MRPL12) or cytochrome
      oxidase had a similar effect. Conversely, expression of the mitochondrial
      uncoupling protein 1 (UCP1) increased oxygen consumption and decreased tumor
      growth. Finally, treatment of tumor bearing animals with dichloroacetate (DCA)
      increased pyruvate consumption in the mitochondria, increased total oxygen
      consumption, increased tumor hypoxia and slowed tumor growth. CONCLUSIONS: We
      interpret these findings to show that non-oncogenic genetic changes that alter
      mitochondrial metabolism can regulate tumor growth through modulation of the
      consumption of oxygen, which appears to be a rate limiting substrate for tumor
      proliferation.

PMID- 19753308
TI  - Pneumococcal bacteremia presenting as acute parotitis and sepsis.
AB  - We report a case of a 33-year-old female with history of Systemic Lupus
      Erythematosus (SLE) presenting with acute febrile illness and unilateral parotid
      gland enlargement progressing to septic shock. The chest imaging showed bilateral
      multilobar infiltrates and Pneumococci were identified in the blood cultures. The
      patient was treated with broad-spectrum antibiotics. The underlying
      imunosupression caused by SLE and long-term steroid treatment could have
      predisposed this patient to invasive Pneumococcal disease.

PMID- 19753309
TI  - SOD2 gene polymorphisms in neovascular age-related macular degeneration and
      polypoidal choroidal vasculopathy.
AB  - PURPOSE: A nonsynonymous coding variant in the manganese superoxide dismutase
      (SOD2) gene (V16A, rs4880) has been implicated in neovascular age-related macular
      degeneration (AMD). However, the findings have been inconsistent. Two studies in
      Japanese populations reported an opposite direction of association of the same
      allele at the V16A variant, whereas one study in a Northern Irish population
      found no effect of the variant on the risk of developing neovascular AMD. To
      address these apparently contradictory reports, we validated the association in a
      Japanese population. METHODS: In a Japanese population, we genotyped the V16A
      variant in 116 neovascular AMD patients, 140 polypoidal choroidal vasculopathy
      (PCV) patients, and 189 control participants. This association was also tested in
      a population of PCV participants to avoid variable findings across studies due to
      underlying sample heterogeneity and because disease phenotype was not well
      described in previous studies. We analyzed a tagging single nucleotide
      polymorphism (SNP) in addition to the V16A variant to capture all common SOD2
      variations verified by the HapMap project. Genotyping was conducted using TaqMan
      technology. Associations were tested using single-SNP and haplotype analyses as
      well as a meta-analysis of the published literature. Population stratification
      was also evaluated in our study population. RESULTS: We found no detectable
      association of the V16A variant or any other common SOD2 variation with either
      neovascular AMD or PCV, as demonstrated by both single-SNP and haplotype
      analyses. Population structure analyses precluded stratification artifacts in our
      study cohort. A meta-analysis of the association between the V16A variant and
      neovascular AMD also failed to detect a significant association. CONCLUSIONS: We
      found no evidence to support the role of any common SOD2 variations including the
      V16A variant in the susceptibility to neovascular AMD or PCV. Our study
      highlights the importance and difficulty in replicating genetic association
      studies of complex human diseases.

PMID- 19753310
TI  - Hypoxia reduces TGFbeta1-induced corneal keratocyte myofibroblast transformation.
AB  - PURPOSE: The purpose of this study was to determine whether transient hypoxia had
      an effect on transforming growth factor beta1 (TGFbeta1)-induced rabbit corneal
      keratocyte myofibroblast transformation. METHODS: Primary isolated rabbit corneal
      keratocytes were cultured in a serum-free medium. The effect of transient hypoxia
      treatment (1% oxygen, 4 h/day) on TGFbeta1 (5 ng/ml)-induced alpha-smooth muscle
      actin (alpha-SM actin) expression was examined by immunofluorescence, flow
      cytometry, and immunocytochemistry 72 h after treatment. We found that hypoxia
      treatment significantly reduced the myofibroblast phenotype and alpha-SM actin
      expression that was induced by TGFbeta1. To explore the possible mechanism for
      this effect, we screened for the effects of hypoxia on several early TGFbeta
      dependent signaling events including activated pSmad3, CREB (cAMP response
      element binding) binding protein (CBP), MAPKs (Mitogen-activated protein kinase),
      and RhoA by co-immunoprecipitation and western blotting. RESULTS: Hypoxia alone
      increased alpha-SM actin expression and the association of pSmad3 to CBP, but it
      did not induce the myofibroblast phenotype. The levels of pERK (the extracellular
      signal-regulated protein kinase) and pSmad3 or the extent of the interaction
      between pSmad3 and CBP induced by TGFbeta1 were not affected by hypoxia whereas
      the activation of RhoA induced by TGFbeta1 was significantly reduced.
      CONCLUSIONS: We conclude that hypoxia can inhibit TGFbeta1-induced corneal
      myofibroblast transformation and alpha-SM actin expression. Our data show that
      this inhibition does not occur by altering Smads or MAPK signaling but possibly
      by reducing the early activation of RhoA.

PMID- 19753311
TI  - Muscarinic acetylcholine receptor 1 gene polymorphisms associated with high
      myopia.
AB  - PURPOSE: Numerous studies, including those using animal models of myopia
      development and human clinical trials, have shown that the non-selective
      muscarinic antagonist atropine is effective in preventing the axial elongation
      that leads to myopia development. Among all of the muscarinic acetylcholine
      receptors (mAChRs), mAChR 1 (M1) was the most effective in preventing myopic eye
      change. Our specific aim in this study was to examine the association between
      high myopia and polymorphisms within the muscarinic acetylcholine receptors 1
      gene (CHRM1). METHODS: The participants comprised of a high myopia group (n=194;
      age range, 17-24 years) having a myopic spherical equivalent greater than 6.5
      diopters (D) and a control group (n=109; age range, 17-25 years) having a myopic
      spherical equivalent less than 0.5 D. Genotyping was performed using an assay-on
      demand allelic discrimination assay. Polymerase chain reaction (PCR) was
      performed using 96 well plates on a thermal cycler. The polymorphisms detected
      were S1 (CHRM1rs11823728), S2 (CHRM1rs544978), S3 (CHRM1rs2186410), and S4
      (CHRM1rs542269). RESULTS: There was a significant difference in the distribution
      of S2 and S4 between the high myopia and control groups (p=2.40 x 10(-6) and 2.38
      x 10(-8), respectively). The odds ratios of AA genotype of S2 and GG genotype of
      S4 were both 0.08 (95% confidence interval [CI]: 0.02-0.29 and 0.02-0.36,
      respectively). Logistic regression test revealed S1, S2, and S4 CHRM1 as all
      being significant in the development of high myopia. Moreover, the distributions
      of haplotype 4 (Ht4; C/A/A/A) differed significantly between the two groups
      (p=3.4 x 10(-5), odds ratio: 0.1, 95% CI: 0.03-0.34). CONCLUSIONS: Our results
      suggest that the S2 and S4 polymorphisms of CHRM1 are associated with
      susceptibility for developing high myopia. S1, S2, and S4 CHRM1 had a co
      operative association with high myopia.

PMID- 19753312
TI  - Mutations that are a common cause of Leber congenital amaurosis in northern
      America are rare in southern India.
AB  - PURPOSE: To test patients from southern India for the presence of mutations that
      most commonly cause Leber congenital amaurosis (LCA) in northern America.
      METHODS: A review of the literature identified 177 unique LCA causing mutations
      in eight different genes: aryl hydrocarbon receptor interacting protein-like 1
      (AIPL1), crumbs homolog 1 (CRB1), cone-rod homeobox (CRX), guanylate cyclase 2D
      (GUCY2D), nephronophthisis 6 (NPHP6), retinol dehydrogenase 12 (RDH12), retinal
      pigment epithelium-specific protein 65 kDa (RPE65), and retinitis pigmentosa
      GTPase regulator interacting protein 1 (RPGRIP1). Allele-specific ligation assay
      and bidirectional sequencing were used to test 38 unrelated LCA patients from
      southern India for 104 of these mutations, which contribute to more than 30% of
      the LCA cases in a northern American population. RESULTS: Only one participant
      was found to harbor one of the 104 mutations in the allele-specific assay
      (homozygous RPE65 Tyr368His). A mutation that was not part of the assay
      (homozygous RPE65 Tyr143Asp) was incidentally detected in a second patient when
      an equivocal signal from one allele on the assay was followed up with automated
      DNA sequencing. CONCLUSIONS: Mutations that contribute to 30% of the LCA cases in
      northern America were detected in only 2.6% of LCA cases in our cohort from
      southern India. There were no instances of IVS26 c.2991+1655 A>G in NPHP6, the
      most commonly detected mutation in LCA. These data suggest that LCA in India is
      caused primarily by a different set of mutations in the same genes associated
      with disease in northern America, or by mutations in other genes that have not
      yet been discovered. Therefore, mutation-specific assays developed for European
      and northern American cohorts may not be suited for testing LCA patients from
      India or other ethnically distinct populations.

PMID- 19753313
TI  - Cis-urocanic acid suppresses UV-B-induced interleukin-6 and -8 secretion and
      cytotoxicity in human corneal and conjunctival epithelial cells in vitro.
AB  - PURPOSE: Urocanic acid (UCA) is a major ultraviolet (UV)-absorbing endogenous
      chromophore in the epidermis and is also an efficacious immunosuppressant. The
      anti-inflammatory and cytoprotective effects of cis-UCA were studied in ocular
      surface cell cultures exposed to UV-B irradiation. METHODS: Human corneal
      epithelial cells (HCE-2) and human conjunctival epithelial cells (HCECs) were
      incubated with 10, 100, 1,000, and 5,000 microg/ml cis-UCA with and without a
      single UV-B irradiation dose. The concentrations of IL-1beta, IL-6, IL-8, and TNF
      alpha in the culture medium and caspase-3 activity in the cell extract sampled
      were measured by enzyme-linked immunosorbent assay (ELISA). Cell viability was
      measured by the colorimetric MTT (3-(4,5-dimethyldiazol- 2-yl)-2,5
      diphenyltetrazolium bromide) assay. RESULTS: UV-B irradiation multiplied
      interleukin IL-6 and IL-8 secretion levels in HCE-2 cells and HCECs as analyzed
      with ELISA. Cell viability as measured by the MTT assay declined by 30%-50% in
      HCE-2 cells and by 20%-40% in HCECs after UV-B irradiation. Moreover, UV-B
      increased caspase-3 activity in both cell types as analyzed with ELISA. Treatment
      with 100 microg/ml cis-UCA completely suppressed IL-6 and IL-8 secretion,
      decreased caspase-3 activity, and improved cell viability against UV-B
      irradiation. No significant effects on IL-6 or IL-8 secretion, caspase-3
      activity, or viability of the non-irradiated cells were observed with 100
      microg/ml cis-UCA in both cell types. The 5,000 microg/ml concentration was
      toxic. CONCLUSIONS: These findings indicate that cis-UCA may represent a
      promising anti-inflammatory and cytoprotective treatment option to suppress UV-B
      induced inflammation and cellular damage in human corneal and conjunctival
      epithelial cells.

PMID- 19753314
TI  - Compound heterozygosity for a novel and a recurrent MFRP gene mutation in a
      family with the nanophthalmos-retinitis pigmentosa complex.
AB  - PURPOSE: To report a new familial case of the recently described autosomal
      recessive syndrome of nanophthalmos-retinitis pigmentosa-foveoschisis-optic disc
      drusen, which arises from compound heterozygosity for Membrane Frizzled-Related
      Protein (MFRP) mutations in a sibling pair of Mexican origin. METHODS:
      Ophthalmological assessment included slit-lamp and dilated fundus examination,
      applanation tonometry, fundus photography, A-mode and B-mode ultrasound
      examination, electroretinogram, fluorescein retinal angiography, optical
      coherence tomography, and electrooculogram in both affected siblings. Molecular
      genetic analysis consisted of PCR amplification and direct automated sequence of
      the complete coding region of the MFRP gene. In addition, allele-specific cloning
      and sequencing techniques were used to characterize a heterozygous MFRP
      frameshift mutation. RESULTS: Clinical examination revealed high hyperopia of >
      +16 diopters while electroretinographic and fluorangiographic studies
      demonstrated a retinal dystrophy compatible with retinitis pigmentosa. Ultrasound
      examination showed nanophthalmos (eye axial length <15 mm) and optic disc drusen
      while optical coherence tomography evidenced cystoid macular edema. Nucleotide
      sequencing in DNA from both affected siblings disclosed the presence of two MFRP
      mutations: a novel heterozygous point mutation predicting a nonsense change from
      tyrosine (TAC) to a stop signal (TAA) at codon 317, and a heterozygous 1 bp
      deletion in exon 5, predicting a prematurely truncated protein
      (p.Asn167ThrfsX25). DISCUSSION: The third known family with the syndrome of
      nanophthalmos-retinitis pigmentosa-foveoschisis-optic disc drusen is presented.
      This is the first demonstration of compound heterozygosity for MFRP mutations as
      the source of the disease. The affected siblings described here are the youngest
      patients with the disease reported to date and the comparison of their clinical
      data with previous individuals with this syndrome suggest that some aspects of
      the phenotype are probably age-dependent.

PMID- 19753315
TI  - Disease-causing mutations in the CLRN1 gene alter normal CLRN1 protein
      trafficking to the plasma membrane.
AB  - PURPOSE: Mutations of clarin 1 (CLRN1) cause Usher syndrome type 3 (USH3). To
      determine the effects of USH3 mutations on CLRN1 function, we examined the
      cellular distribution and stability of both normal and mutant CLRN1 in vitro. We
      also searched for novel disease-causing mutations in a cohort of 59 unrelated
      Canadian and Finnish USH patients. METHODS: Mutation screening was performed by
      DNA sequencing. For the functional studies, wild-type (WT) and mutant CLRN1 genes
      were expressed as hemagglutinin (HA) tagged fusion proteins by transient
      transfection of BHK-21 cells. Subcellular localization of CLRN1-HA was examined
      by confocal microscopy. The N-glycosylation status of CLRN1 was studied by using
      the N-glycosidase F (PNGase F) enzyme and western blotting. Cycloheximide
      treatment was used to assess the stability of CLRN1 protein. RESULTS: We found
      three previously reported pathogenic mutations, p.A123D, p.N48K, and p.Y176X, and
      a novel sequence variant, p.L54P, from the studied USH patients. The WT HA-tagged
      CLRN1 was correctly trafficked to the plasma membrane, whereas mutant CLRN1-HA
      proteins were mislocalized and retained in the endoplasmic reticulum. PNGase F
      treatment of CLRN1-HA resulted in an electrophoretic mobility shift consistent
      with sugar residue cleavage in WT and in all CLRN1 mutants except in p.N48K
      mutated CLRN1, in which the mutation abolishes the glycosylation site. Inhibition
      of protein expression with cycloheximide indicated that WT CLRN1-HA remained
      stable. In contrast, the CLRN1 mutants showed reduced stability. CONCLUSIONS: WT
      CLRN1 is a glycoprotein localized to the plasma membrane in transfected BHK-21
      cells. Mutant CLRN1 proteins are mislocalized. We suggest that part of the
      pathogenesis of USH3 may be associated with defective intracellular trafficking
      as well as decreased stability of mutant CLRN1 proteins.

PMID- 19753316
TI  - A novel mutation in GRK1 causes Oguchi disease in a consanguineous Pakistani
      family.
AB  - PURPOSE: The purpose of this study was to identify the underlying molecular
      genetic defect in a large consanguineous Pakistani family with Oguchi disease who
      had been given a diagnosis of autosomal recessive retinitis pigmentosa. METHODS:
      The family was genotyped with the Affymetrix 10K single nucleotide polymorphism
      array. Fine-mapping of a common homozygous region on chromosome 13q was performed
      using fluorescent microsatellite markers. Mutation analysis was done by direct
      sequencing of the candidate gene GRK1 located in the region. The segregation of a
      novel mutation in the family and the frequency of the identified mutation in the
      Pakistani population were determined by StuI RFLP analysis. RESULTS: Genetic
      mapping supported the diagnosis of typical Oguchi disease in a Pakistani family
      and also resulted in the identification of a novel nonsense mutation (c.614C>A;
      p.S205X) in exon 1 of GRK1. This mutation is predicted to result in premature
      termination of the protein product, thereby affecting the phototransduction
      cascade. A clinical reappraisal of the family revealed that all patients
      homozygous for this variant had Oguchi disease. CONCLUSIONS: This is the first
      report to describe a mutation causing typical Oguchi disease in a large
      consanguineous Pakistani family. This mutation segregated in eight affected
      members.

PMID- 19753317
TI  - ArterioVenous Malformation within Jejunal Diverticulum: an unusual cause of
      massive gastrointestinal bleeding.
AB  - Massive gastrointestinal (GI) bleeding can occur with multiple jejunal
      diverticulosis. However, significant bleeding in the setting of few diverticulae
      is very unusual and rare. We report a case of massive gastrointestinal bleeding
      from an arteriovenous malformation (AVM) within a jejunal diverticulum to
      underscore the significance of such coexisting pathologies. Mesenteric angiogram
      was chosen to help identify the source of bleeding and to offer an intervention.
      Despite endovascular coiling, emergent intestinal resection of the bleeding
      jejunal segment was warranted to ensure definitive treatment. However several
      reports have shown jejunal diverticulosis as a rare cause of massive GI bleeding.
      The coexistence of jejunal diverticulum and AVM is rare and massive bleeding from
      an acquired Dieulafoy-like AVM within a diverticulum has never previously been
      described. Awareness of Dieulafoy-like AVM within jejunoileal diverticulosis is
      useful in preventing delay in treatment.

PMID- 19753318
TI  - Rational design of improved pharmabiotics.
AB  - Herein we review the most recent advances in probiotic research and applications
      with particular emphasis on the novel concept of patho-biotechnology: the
      application of pathogen-derived (ex vivo and in vivo) stress survival strategies
      for the design of more technologically robust and effective probiotic cultures
      with improved biotechnological and clinical applications.

PMID- 19753319
TI  - Concentration polarization of high-density lipoprotein and its relation with
      shear stress in an in vitro model.
AB  - The purpose of this study was to determine the concentration polarization of high
      density lipoprotein (HDL) at the surface of the carotid artery under conditions
      of steady flow and to establish its relationship with shear stress using an in
      vitro vascular simulation model of carotid bifurcation. Shear stress, HDL
      concentration at the surface, and the ratio of HDL concentration at the surface
      to concentration in bulk flow were measured at different locations within the
      model under high-speed (1.451 m/s) and low-speed (0.559 m/s) flow. HDL showed
      concentration polarization at the surface of the carotid artery model,
      particularly in the internal carotid artery sinus. With decreasing flow velocity,
      the shear stress at the surface also decreased, and HDL concentration
      polarization increased. The concentration polarization of HDL was negatively and
      strongly correlated with shear stress at both low- (r = -0.872, P < .001) and
      high-speed flow (r = -0.592, P = .0018).

PMID- 19753320
TI  - An evaluation of cellular neural networks for the automatic identification of
      cephalometric landmarks on digital images.
AB  - Several efforts have been made to completely automate cephalometric analysis by
      automatic landmark search. However, accuracy obtained was worse than manual
      identification in every study. The analogue-to-digital conversion of X-ray has
      been claimed to be the main problem. Therefore the aim of this investigation was
      to evaluate the accuracy of the Cellular Neural Networks approach for automatic
      location of cephalometric landmarks on softcopy of direct digital cephalometric X
      rays. Forty-one, direct-digital lateral cephalometric radiographs were obtained
      by a Siemens Orthophos DS Ceph and were used in this study and 10 landmarks (N, A
      Point, Ba, Po, Pt, B Point, Pg, PM, UIE, LIE) were the object of automatic
      landmark identification. The mean errors and standard deviations from the best
      estimate of cephalometric points were calculated for each landmark. Differences
      in the mean errors of automatic and manual landmarking were compared with a 1-way
      analysis of variance. The analyses indicated that the differences were very
      small, and they were found at most within 0.59 mm. Furthermore, only few of these
      differences were statistically significant, but differences were so small to be
      in most instances clinically meaningless. Therefore the use of X-ray files with
      respect to scanned X-ray improved landmark accuracy of automatic detection.
      Investigations on softcopy of digital cephalometric X-rays, to search more
      landmarks in order to enable a complete automatic cephalometric analysis, are
      strongly encouraged.

PMID- 19753321
TI  - Interleukin (IL)-4 induces leukocyte infiltration in vivo by an indirect
      mechanism.
AB  - Interleukin (IL)-4 is a cytokine known mainly for its anti-inflammatory activity.
      Using the in vivo murine air pouch model, we found that IL-4 significantly
      increased the number of leukocytes after 9 hours of treatment, consisting mainly
      of neutrophil (60%) and monocytic (40%) cell populations. Using an antibody
      array, we found that the expression of several analytes (predominantly CCL2) was
      increased by IL-4 before the arrival of leukocytes. The IL-4-induced expression
      of CCL-2 was confirmed by ELISA. Air pouch resident lining cells were harvested
      and were found to express IL-4Ralpha. CCL2 mRNA expression was monitored in
      lining cells, cells isolated from the air pouch skin, in RAW264.7 macrophage and
      in epithelial Mode-K cells and its expression was increased in response to IL-4
      in all conditions. We conclude that IL-4 can attract leukocytes in vivo by an
      indirect mechanism involving the production of several analytes by, at least,
      resident cells.

PMID- 19753322
TI  - Dichorionic diamniotic twin pregnancy discordant for bladder exstrophy.
AB  - A 38 year-old woman presented with a dichorionic diamniotic twin pregnancy at
      gestational age of 32 weeks concerning for an abdominal wall mass in one of the
      twins. Initial ultrasound evaluation was suspicious for an omphalocele, but the
      affected twin was found to have bladder exstrophy at birth. This illustrates the
      difficulties of accurate prenatal diagnosis of bladder exstrophy in a twin
      pregnancy at a late gestation.

PMID- 19753323
TI  - Cortical Membrane Potential Dynamics and Laminar Firing during Object Motion.
AB  - When an object is introduced moving in the visual field of view, the object maps
      with different delays in each of the six cortical layers in many visual areas by
      mechanisms that are poorly understood. We combined voltage sensitive dye (VSD)
      recordings with laminar recordings of action potentials in visual areas 17, 18,
      19 and 21 in ferrets exposed to stationary and moving bars. At the area 17/18
      border a moving bar first elicited an ON response in layer 4 and then ON
      responses in supragranular and infragranular layers, identical to a stationary
      bar. Shortly after, the moving bar mapped as moving synchronous peak firing
      across layers. Complex dynamics evolved including feedback from areas 19/21, the
      computation of a spatially restricted pre-depolarization (SRP), and firing in the
      direction of cortical motion prior to the mapping of the bar. After 350 ms, the
      representations of the bar (peak firing and peak VSD signal) in areas 19/21 and
      17/18 moved over the cortex in phase. The dynamics comprise putative mechanisms
      for automatic saliency of novel moving objects, coherent mapping of moving
      objects across layers and areas, and planning of catch-up saccades.

PMID- 19753324
TI  - Sub-Millisecond Firing Synchrony of Closely Neighboring Pyramidal Neurons in
      Hippocampal CA1 of Rats During Delayed Non-Matching to Sample Task.
AB  - Firing synchrony among neurons is thought to play functional roles in several
      brain regions. In theoretical analyses, firing synchrony among neurons within sub
      millisecond precision is feasible to convey information. However, little is known
      about the occurrence and the functional significance of the sub-millisecond
      synchrony among closely neighboring neurons in the brain of behaving animals
      because of a technical issue: spikes simultaneously generated from closely
      neighboring neurons are overlapped in the extracellular space and are not easily
      separated. As described herein, using a unique spike sorting technique based on
      independent component analysis together with extracellular 12-channel multi
      electrodes (dodecatrodes), we separated such overlapping spikes and investigated
      the firing synchrony among closely neighboring pyramidal neurons in the
      hippocampal CA1 of rats during a delayed non-matching to sample task. Results
      showed that closely neighboring pyramidal neurons in the hippocampal CA1 can co
      fire with sub-millisecond precision. The synchrony generally co-occurred with the
      firing rate modulation in relation to both internal (retention and comparison)
      and external (stimulus input and motor output) events during the task. However,
      the synchrony occasionally occurred in relation to stimulus inputs even when rate
      modulation was clearly absent, suggesting that the synchrony is not simply
      accompanied with firing rate modulation and that the synchrony and the rate
      modulation might code similar information independently. We therefore conclude
      that the sub-millisecond firing synchrony in the hippocampus is an effective
      carrier for propagating information - as represented by the firing rate
      modulations - to downstream neurons.

PMID- 19753325
TI  - Could Sex Differences in White Matter be Explained by g ratio?
AB  - Recent studies with magnetic resonance imaging suggest that age-related changes
      in white matter during male adolescence may indicate an increase in g ratio
      wherein the radial growth of an axon outpaces a corresponding increase in myelin
      thickness. We review the original Rushton (1951) model where a g ratio of
      approximately 0.6 represents an optimal relationship between the axon and fibre
      diameters vis-a-vis conduction velocity, and point out evidence indicating
      slightly higher g ratio in large-diameter fibres. We estimate that fibres with a
      diameter larger than 9.6 mum will have a relatively thinner myelin sheath, and
      brains with increasingly larger proportions of such large-diameter fibres will
      have progressively lower concentration of myelin. We conclude by pointing out
      possible implications of "suboptimal" g ratio for the emergence of
      "disconnection" disorders, such as schizophrenia, in late adolescence.

PMID- 19753326
TI  - Informational lesions: optical perturbation of spike timing and neural synchrony
      via microbial opsin gene fusions.
AB  - Synchronous neural activity occurs throughout the brain in association with
      normal and pathological brain functions. Despite theoretical work exploring how
      such neural coordination might facilitate neural computation and be corrupted in
      disease states, it has proven difficult to test experimentally the causal role of
      synchrony in such phenomena. Attempts to manipulate neural synchrony often alter
      other features of neural activity such as firing rate. Here we evaluate a single
      gene which encodes for the blue-light gated cation channel channelrhodopsin-2 and
      the yellow-light driven chloride pump halorhodopsin from Natronobacterium
      pharaonis, linked by a 'self-cleaving' 2A peptide. This fusion enables
      proportional expression of both opsins, sensitizing neurons to being bi
      directionally controlled with blue and yellow light, facilitating proportional
      optical spike insertion and deletion upon delivery of trains of precisely-timed
      blue and yellow light pulses. Such approaches may enable more detailed
      explorations of the causal role of specific features of the neural code.

PMID- 19753327
TI  - The impact of early life family structure on adult social attachment,
      alloparental behavior, and the neuropeptide systems regulating affiliative
      behaviors in the monogamous prairie vole (microtus ochrogaster).
AB  - Early social attachments lie at the heart of emotional and social development in
      many mammals, including humans. In nature, monogamous prairie voles (Microtus
      ochrogaster) experience considerable natural variation in early social attachment
      opportunities due to differences in family structure [e.g., single-mothers (SM),
      solitary breeding pairs, and communal groups]. We exploited some of this natural
      variation in family structure to examine the influence of early social
      environment on the development of adult social behavior. First, we characterized
      the parental care received by pups reared biparentally (BP) or by SM in the
      laboratory. Second, we examined whether BP- and SM-reared offspring differed in
      adult nurturing, bonding, and emotional behaviors. Finally, we investigated the
      effects of rearing condition on neuropeptide systems that regulate adult social
      behavior [oxytocin (OT), vasopressin, and corticotropin-releasing factor, (CRF)].
      Observations revealed that SM-reared pups were exposed more frequently (P <
      0.01), licked and groomed less (P < 0.01), and matured more slowly (P < 0.01)
      than BP-reared pups. In adulthood, there were striking socio-behavioral
      differences: SM-reared females showed low spontaneous, pup-directed alloparental
      behavior (P < 0.01) and both males and females from the SM-reared condition
      showed delayed partner preference formation. While rearing did not impact
      neuropeptide receptor densities in the ventral forebrain as we predicted, SM
      reared animals, particularly females, had increased OT content (P < 0.01) and
      greater dorsal raphe CRF2 densities (P < 0.05) and both measures correlated with
      licking and grooming experienced during the first 10 days of life. These results
      suggest that naturalistic variation in social rearing conditions can introduce
      diversity into adult nurturing and attachment behaviors.

PMID- 19753328
TI  - The Relationship between Dendritic Branch Dynamics and CPEB-Labeled RNP Granules
      Captured in Vivo.
AB  - Cytoplasmic Polyadenylation Element Binding protein (CPEB) is an RNA binding
      protein involved in dendritic delivery of mRNA and activity-dependent,
      polyadenylation-induced translation of mRNAs in the dendritic arbor. CPEB affects
      learning and memory and impacts neuronal morphological and synaptic plasticity.
      In neurons, CPEB is concentrated in ribonucleoprotein (RNP) granules that
      distribute throughout the dendritic arbor and localize near synapses, suggesting
      that the trafficking of RNP granules is important for CPEB function. We tagged
      full-length CPEB and an inactive mutant CPEB with fluorescent proteins, then
      imaged rapid dendritic branch dynamics and RNP distribution using two-photon time
      lapse microscopy of neurons in the optic tectum of living Xenopus laevis
      tadpoles. Though the inactive CPEB mutant transports mRNA in the dendritic arbor,
      its expression interferes with CPEB-dependent translation because it is incapable
      of activity-triggered mRNA polyadenylation. In dendrites, the distributions of
      the active and inactive CPEB-containing RNP granules do not differ; the RNP
      granules are dense and their positions do not correlate with sites of rapid
      dendritic branch dynamics or the eventual fate of the dendritic branches. Because
      CPEB's sensitivity to activity-dependent signaling does not alter its dendritic
      distribution, it indicates that active sites in the dendritic arbor are not
      targeted for RNP granule localization. Nevertheless, inactive CPEB accumulates in
      granules in terminal dendritic branches, supporting the hypothesis that upon
      activation CPEB and its mRNA cargo are released from granules and are then
      available for dendritic translation.

PMID- 19753329
TI  - Changes in frequency of spontaneous oscillations in procerebrum correlate to
      behavioural choice in terrestrial snails.
AB  - The aim of our study was to understand functional significance of spontaneous
      oscillations of local field potential in the olfactory brain lobe of terrestrial
      snail, the procerebrum (PC). We compared changes in frequency of oscillations in
      semi-intact preparations from snails trained to percept the same conditioned odor
      as positive (associated with food reinforcement) or negative (associated with
      noxious reinforcement). In vivo recordings in freely behaving naive snails showed
      a significant decrease of spontaneous PC oscillations frequency during a stage of
      tentacle withdrawal to odor presentation. In in vitro preparations from naive
      snails, a similar decrease in frequency of the PC oscillations to odor
      presentation was observed. Changes in frequency of the oscillations to cineole
      presentations in the "aversive" group of snails (demonstrating withdrawal) were
      much more pronounced than in naive snails. No significant difference in responses
      to 5% and 20% cineole was noted. Changes in the spontaneous oscillations
      frequency in the snails trained to respond with positive reaction (approach) to
      cineole depended on the concentration of the applied odor, and these responses
      were qualitatively similar to responses of other groups during the first 10 s of
      responses to odor, but significantly different (increase in PC oscillations
      frequency) from the responses of the aversively trained and naive snails in the
      interval 11-30 s, which corresponds to the end of the tentacle withdrawal and
      timing of decision making (approach or escape) in the free behaving snails.
      Obtained results suggest that frequency of the PC lobe spontaneous oscillations
      correlate to the choice of behavior in snails: withdrawal (decrease in frequency)
      or approach (increase in frequency) to the source of odor.

PMID- 19753330
TI  - Endothelium as target for large-conductance calcium-activated potassium channel
      openers.
AB  - The endothelium is a highly active organ responsible for vasculatory tone and
      structure, angiogenesis, as well as hemodynamic, humoral, and inflammatory
      responses. The endothelium is constantly exposed to blood flow, sheer stress and
      tension. Endothelial cells are present as a vasculature in every tissue of the
      body and react to and control its microenvironment. A variety of ion channels are
      present in the plasma membranes of endothelial cells. These include potassium
      channels such as inwardly rectifying potassium (K(ir)) channels, voltage
      dependent (K(v)) channels, ATP-regulated potassium (K(ATP)) channels and three
      types of calcium-activated potassium channels (K(Ca)), the large (BK(Ca)),
      intermediate (IK(Ca)), and small (SK(Ca)) -conductance potassium channels.
      Potassium current plays a critical role in action potentials in excitable cells,
      in setting the resting membrane potential, and in regulating neurotransmitter
      release. Mitochondrial isoforms of potassium channel contribute to the
      cytoprotection of endothelial cells. Prominent among potassium channels are
      families of calcium-activated potassium channels, and especially large
      conductance calcium-activated potassium channels. The modulation of BK(Ca)
      channels, which are voltage- and calcium-dependent, has been intensively studied.
      The BK(Ca) channels show large expression dynamics in endothelial cells and
      tissue-specific expression of large numbers of alternatively spliced isoforms. In
      this review, a few examples of the modulatory mechanisms and physiological
      consequences of the expression of BK(Ca) channels are discussed in relation to
      potential targets for pharmacological intervention.

PMID- 19753331
TI  - Bradykinin-related peptides up-regulate the expression of kinin B1 and B2
      receptor genes in human promonocytic cell line U937.
AB  - Kinins, universal mediators of inflammation, are recognized by two kinds of
      receptors, B1 and B2, which have been found to be expressed in numerous cell
      types of several species. However, the knowledge of the regulation of these
      receptors in leukocytes is still not satisfactory. In the current work, we have
      demonstrated a constitutive production of B2 receptor mRNA in the human
      promonocyte U937 cells and its two-fold augmentation after cell differentiation
      with retinoic acid and phorbol ester. Bradykinin and des-Arg(10)-kallidin induced
      the expression of both B2 and B1 receptors in cells before and after
      differentiation. Generally, the undifferentiated cells were more susceptible to
      bradykinin-dependent induction of kinin receptors (increases by approximately
      250% and 200% for B2 and B1 receptors, respectively). The induction, by approx.
      200%, of B1 receptor by des-Arg(10)-kallidin was detected on both mRNA and
      protein levels. In addition, an unexpected strong induction of B2 receptor by
      this compound was observed in the retinoic acid- and phorbol ester-differentiated
      cells (by 150% and 200%, respectively) that suggests a possible autoregulation of
      kinin receptors by own agonists during the inflammatory state. On the other hand,
      a strong enhancement of the expression of both receptors by interleukin 1beta,
      especially in the phorbol ester-differentiated cells, indicates the involvement
      of kinin receptors in the propagation of the inflammatory processes.

PMID- 19753332
TI  - Natural phenolic acids may increase serum estradiol level in ovariectomized rats.
AB  - Natural phenolic acids are commonly present in plants consumed in the diet.
      Recently we have observed that different natural phenolic acids exert
      differential effects on the body mass gain in ovariectomized and non
      ovariectomized female rats. The aim of the present study was to investigate the
      effects of ferulic, caffeic, p-coumaric and chlorogenic acids on serum estradiol
      and total cholesterol levels in ovariectomized and non-ovariectomized rats. The
      experiments were carried out on 3-month old female Wistar Cmd:(WI)WU rats,
      divided into following groups (n=8 in each group): non-ovariectomized control
      rats and non-ovariectomized rats receiving ferulic, caffeic, p-coumaric or
      chlorogenic acids, sham-operated control rats, ovariectomized control rats and
      ovariectomized rats receiving the same phenolic acids. The phenolic acids were
      administered at a dose of 10 mg/kg p.o. daily for 4 weeks. Serum estradiol and
      total cholesterol levels on the next day after the last administration of the
      phenolic acids were examined. The phenolic acids did not affect serum estradiol
      or total cholesterol levels in non-ovariectomized rats. In ovariectomized rats,
      caffeic acid and to a lesser extent p-coumaric acid increased serum estradiol
      level, which effect correlated with a decreased body mass gain. All the phenolic
      acids decreased serum cholesterol level in ovariectomized rats. Concluding, the
      anti-obesity activity of some phenolic acids may be, at least partially,
      connected with estrogenic pathways.

PMID- 19753333
TI  - Mechanosensitivity of cell membrane may govern creep-strain recovery, osmotic
      expansion and lysis.
AB  - A simple theoretical model considering cell membrane mechanosensitivity can
      accurately describe published experimental data on membrane area creeping and
      recovery, and on osmotic expansion and rupture. The model to data fit reveals
      real values of membrane tension and elasticity modulus, and the parameters
      describing membrane organization and kinetics of mechanosensitive membrane
      traffic, including small solute transport, water permeability, endocytosis,
      exocytosis, and caveolae formation. This estimation allows for separation and
      quantitative analysis of the participation of different processes constituting
      the response of plasmalemma to short time-scale membrane load. The predicted
      properties of the model were verified for membrane stretching at different
      osmotic pressures. Finally, a simple hypothesis concerning stressed cell membrane
      breakdown is postulated.

PMID- 19753334
TI  - TGF-beta(1), IL-10 and IL-4 in colostrum of allergic and nonallergic mothers.
AB  - OBJECTIVE: To determine transforming growth factor (TGF) beta(1), interleukin
      (IL) 4, and IL-10 concentrations in human milk and to assess the relationship
      between allergic disorders in mothers and the content of the interleukins in
      their milk. MATERIAL AND METHODS: Thirty allergic and 46 healthy mothers were
      included in the study. Colostrum was collected 2-3 days after delivery. Cytokine
      concentrations were determined with commercial enzyme-linked immunosorbent
      systems. RESULTS: TGF-beta(1)was found in milk from 23 women in the control group
      (53.49%) and 11 in the allergy group (37.93%). When TGF-beta(1) was present, the
      median concentration was higher in the allergy group than in the control (61.5
      and 30.4 pg/mL, respectively; P < 0.004). IL-10 was present in the colostrum of
      all the women and the median IL-10 concentration did not differ between the
      allergy (50.5 pg/mL) and control (51.5 pg/mL) groups. The probability of
      occurrence of a positive IL-4 value in the allergy group was greater than in the
      control group (chi-squared [df=1] = 2.60, P < 0.053). Median IL-4 level did not
      differ significantly between the two groups (0.5 and 0.5 pg/mL respectively).
      CONCLUSIONS: TGF-beta(1) was detected less often in the colostrum of allergic
      mothers than in that of mothers without allergy (but the difference was not
      statistically significant). IL-4 was found more often in the colostrum of
      allergic mothers than nonallergic ones. The allergy status did not correlate with
      IL-10 concentration.

PMID- 19753335
TI  - H3K4 histone methylation in oral squamous cell carcinoma.
AB  - Methylation of specific lysine residues in histone tails has been proposed to
      function as a stable epigenetic marker that directs biological functions altering
      chromatin structure. Recent findings have implicated alteration in
      heterochromatin formation as a contributing factor in cancer development. In
      order to verify whether changes in the overall level of H3K4 histone methylation
      could be involved in oral squamous carcinoma, the levels of H3K4me1, me2 and me3
      were measured in oral squamous carcinoma, leukoplakias and normal tissues. The
      levels of H3K4me2 and me3 were significantly different in oral squamous cell
      carcinoma in comparison with normal tissue: the level of H3K4me2 was increased
      while that of H3K4me3 decreased. No significant differences could be found
      between the two types of tissues in the level of H3K4me1. A similar trend was
      found in the leukoplakias that appeared more like the pathological than normal
      tissue. These results support the idea that alteration of chromatin structure
      could contribute to oncogenic potential.

PMID- 19753339
TI  - Triarylamine: a promising core unit for efficient photovoltaic materials.
AB  - Triarylamine has been widely used in opto- and electro-active materials for its
      good electron donating and transporting capability, as well as its special
      propeller starburst molecular structure. Recently, organic photovoltaic
      functional materials with triarylamine as electron donor have aroused great
      interest and become the focus of intensive research in the field of solar cells.
      These materials have significantly reinforced the conversion efficiency of next
      generation solar cells, especially dye sensitized solar cells. This Feature
      Article describes new synthetic methods and the application of starburst
      triarylamines, highlighting the applications in photovoltaic and optoelectrical
      fields.

PMID- 19753340
TI  - Recent extensions of the Morita-Baylis-Hillman reaction.
AB  - Significant progress in the development of the Morita-Baylis-Hillman (MBH)
      reaction has been made in the past decade. Many new variations of the MBH
      reaction have been well exploited, affording unexpected products and novel
      cyclized adducts in some cases, known as "abnormal MBH reactions". The formation
      of abnormal MBH adducts depends on the nature of the substrates and the employed
      catalytic system. This article will summarize recent advances in and mechanistic
      insights into such "abnormal" MBH reactions, including double-MBH reactions, sila
      MBH reactions, abnormal aza-MBH reactions and tandem MBH pathways.

PMID- 19753341
TI  - Face selective translation of a cyclodextrin ring along an axle.
AB  - A cyclodextrin ring was face-selectively transferred between two stations linked
      by a 2-methylpyridinium group on an axle molecule.

PMID- 19753342
TI  - Metal-free hydrogen activation and hydrogenation of imines by 1,8
      bis(dipentafluorophenylboryl)naphthalene.
AB  - In the presence of 2,2,6,6-tetramethylpiperidine (TMP) 1,8
      bis(dipentafluorophenylboryl)naphthalene has been found to activate H2 and to
      hydrogenate various imines under mild conditions.

PMID- 19753343
TI  - Fabrication of 3D supramolecular hybrid particle microstructures with
      controllable morphology and dimensions.
AB  - Discrete 3D supramolecular hybrid particle structures with controllable
      morphology and dimensions were fabricated and their ability to encapsulate guest
      molecules was demonstrated.

PMID- 19753344
TI  - A novel Kolbe reaction pathway for a selective one- and two-electron reduction of
      azo compounds.
AB  - The selective one- and two-electron reduction of azo-pyridine and azo-1,8
      naphthyridine with anionic CH3COO- by the Kolbe reaction has been established for
      the first time, and reaction mechanisms are presented.

PMID- 19753345
TI  - Synthesis and preliminary biological evaluations of [18F]-1-deoxy-1-fluoro-scyllo
      inositol.
AB  - A novel PET radiotracer, [18F]-1-deoxy-1-fluoro-scyllo-inositol, was synthesized
      via a one-pot reaction in 16 +/- 3% uncorrected radiochemical yield within 80
      minutes; although this compound revealed low brain penetration it shows promise
      in rodent tumour models for breast cancer imaging.

PMID- 19753346
TI  - Organic polymer composites as robust, non-covalent supports of metal salts.
AB  - A novel organic polymer composite for the encapsulation of metal catalysts and
      applications to synthesis are described here.

PMID- 19753347
TI  - Unique porous microspheres with dense core and a porous layer prepared by a novel
      S/O/W emulsion technique.
AB  - Porous polymeric microspheres with unique core-shell structures (similar to
      Kusudama--Japanese paper balls) have been fabricated via a new solid-in-oil-in
      water (S/O/W) emulsion technique.

PMID- 19753349
TI  - Oligosilylated group 4 titanocenes in the oxidation state +3.
AB  - Reactions of oligosilylanions with Cp2TiCl2 led to the formation of ate-complexes
      of silylated titanocenes, which form upon silylation of the intermediate
      K[Cp2TiCl2].18-crown-6.

PMID- 19753348
TI  - Synthesis of a monophosphoryl lipid A derivative and its conjugation to a
      modified form of a tumor-associated carbohydrate antigen GM3.
AB  - An efficient synthesis of a derivative of monophosphoryl lipid A suitable for
      coupling to various structures for the construction of glycoconjugate vaccines
      and its conjugation with an N-modified form of the tumor-associated antigen GM3
      is presented.

PMID- 19753350
TI  - Intercepting the synthesis of triazine dendrimers with nucleophilic
      pharmacophores: a general strategy toward drug delivery vehicles.
AB  - The camptothecin ester of isonipecotic acid is installed on a triazine dendrimer
      intermediate obtained through an iterative, scalable route to ultimately yield
      cationic and PEGylated targets with activities in cell culture comparable to free
      drug.

PMID- 19753351
TI  - Insertion reactions of a two-coordinate iron diaryl with dioxygen and carbon
      monoxide.
AB  - The iron(II) diaryl FeAr'2 (1) (Ar' = C6H3-2,6-(C6H3-2,6-(i)Pr2)2) reacts cleanly
      with O2 or CO to afford the monomeric, two-coordinate bis(aryloxide) Fe(OAr')2
      (2) or the eta2-acyl-carbonyl complex (eta2-Ar'C=O)2Fe(CO)2 (3) via oxygen or CO
      insertion into the Fe-C bonds; complex 2 has a strictly linear geometry and shows
      remarkable resistance to O2 oxidation.

PMID- 19753352
TI  - A mass spectrometric investigation of the ability of metal complexes to modulate
      transcription factor activity.
AB  - ESI mass spectrometry was used to assess the ability of metal complexes to
      inhibit binding of a transcription factor to a DNA molecule containing its
      recognition sequence.

PMID- 19753353
TI  - Electrochemical patterning of gold nanoparticles on transparent single-walled
      carbon nanotube films.
AB  - We report a simple, low cost, electrochemical deposition method to pattern gold
      nanoparticles on flexible, transparent, single-walled carbon nanotube (SWCNT)
      films, and demonstrate the application of the gold-patterned SWCNT films as
      surface-enhanced Raman spectroscopy substrates and biosensing electrodes for non
      enzymatic glucose detection.

PMID- 19753354
TI  - Synthesis and electrochemical properties of TTF modified oligodeoxynucleotides.
AB  - A new approach for labelling oligodeoxynucleotides with tetrathiafulvalene (TTF)
      units is presented, generating single and double strand structures with
      distinctive electrochemical signatures.

PMID- 19753355
TI  - Gold nanoparticles supported on Cs2CO3 as recyclable catalyst system for
      selective aerobic oxidation of alcohols at room temperature.
AB  - NaAuCl4/Cs2CO3 was found to be a simple bench top, recyclable and selective
      catalyst system for the aerobic oxidation of various types of alcohols into their
      corresponding aldehydes and ketones at room temperature without the need for any
      further polymeric and/or oxidic support.

PMID- 19753356
TI  - Two diamino-substituted lithiocarbanions in one molecule.
AB  - tert-Butyllithium deprotonates bis(3-methyl-1,3-diazacyclohex-1-yl)methane and
      its five-ring analogue regioselectively at both endocyclic NCH2N units; a
      deprotonation intermediate has been isolated and structurally characterised.

PMID- 19753357
TI  - Synthesis and structural characterization of a binuclear iridium complex with
      bridging, bidentate N-heterocyclic carbene coordination of 2,2':6',2''
      terpyridine.
AB  - Thermal activation of terpyridine in the presence of an unsaturated Ir(III)
      fragment stabilized by a hydrotris(pyrazolyl) borate ligand gives rise to
      mononuclear complex and binuclear , in which the polypyridine behaves,
      respectively, as a mono- or a bi-dentate N-heterocyclic carbene.

PMID- 19753358
TI  - Crosslinked hybrid polymer matrices with nanostructure directing abilities for
      lanthanum hydroxide growth.
AB  - Polysiloxane-PEO hybrid polymers were used as precipitation environments for
      La(OH)3 nanoobjects.

PMID- 19753359
TI  - Bio-bar-code functionalized magnetic nanoparticle label for ultrasensitive flow
      injection chemiluminescence detection of DNA hybridization.
AB  - A signal amplification strategy based on bio-bar-code functionalized magnetic
      nanoparticles as labels holds promise to improve the sensitivity and detection
      limit of the detection of DNA hybridization and single-nucleotide polymorphisms
      by flow injection chemiluminescence assays.

PMID- 19753360
TI  - Low band gap dithieno[3,2-b:2',3'-d]silole-containing polymers, synthesis,
      characterization and photovoltaic application.
AB  - A series of low band gap silole-containing polymers were synthesized with
      different alkyl side chains and a power conversion efficiency (PCE) of 3.43% was
      obtained.

PMID- 19753361
TI  - Building addressable libraries: a site-selective click-reaction strategy for
      rapidly assembling mass spectrometry cleavable linkers.
AB  - A click-reaction was site-selectively carried out on 1000 and 12,000
      microelectrode arrays and characterized using TOF-SIMS.

PMID- 19753362
TI  - Gelation, functionalization, and solution behaviors of nanodiamonds with ionic
      liquids.
AB  - Detonation nanodiamond particles can be formed a gel with ionic liquids, which
      can easily be fabricated. The imidazolium bromide-functionalized nanodiamond
      particles are dispersed in ionic liquids with uniform size-distribution.

PMID- 19753363
TI  - Variable length ligands: a new class of bridging ligands for supramolecular
      chemistry and crystal engineering.
AB  - A series of 1- and 2-D coordination polymers containing a functionalised diaza-18
      crown-6 ligand show guest dependent variation of the ligand length.

PMID- 19753364
TI  - Self-assembly of double hydrophobic block copolymers in water-ethanol mixtures:
      from micelles to thermoresponsive micellar gels.
AB  - Micellization and micellar gel formation of poly(styrene)-block-poly(methyl
      methacrylate) [PS-b-PMMA] are demonstrated in a water-ethanol solvent mixture;
      full hydration of the PMMA causes a large radius of gyration resulting in
      micellar gel formation at only 1 wt% polymer concentration.

PMID- 19753365
TI  - Eliminating the need for independent counterions in the construction of metal
      organic rotaxane frameworks (MORFs).
AB  - The combination of a disulfonated-dibenzo-24crown-8 ether wheel and a dicationic
      1,2-bis(pyridinium)ethane axle yields a neutral [2]pseudorotaxane which in
      combination with neutral metallic units such as a Cu(II)benzoate paddlewheel or
      Cu(I)Br unit yields one-dimensional coordination polymers (linear and bent) which
      are the first examples of charge neutral, metal-organic rotaxane frameworks.

PMID- 19753366
TI  - Facile synthesis of stapled, structurally reinforced peptide helices via a
      photoinduced intramolecular 1,3-dipolar cycloaddition reaction.
AB  - We report the first use of a photoinduced 1,3-dipolar cycloaddition reaction in
      "stapling" peptide sidechains to reinforce a model peptide helical structure with
      moderate to excellent yields; the resulting pyrazoline "staplers" exhibit unique
      fluorescence useful in a cell permeability study.

PMID- 19753367
TI  - Platinum-catalysed aerobic 1,2-aminooxygenation of alkenes.
AB  - Platinum(II) salts in combination with copper salts and molecular oxygen catalyse
      an unprecedented intramolecular transfer of heteroatoms to alkenes to yield
      aminooxygenation products under sustainable conditions.

PMID- 19753368
TI  - Catalytic membrane-installed microchannel reactors for one-second allylic
      arylation.
AB  - A variety of catalytic membranes of palladium-complexes with linear polymer
      ligands were prepared inside a microchannel reactor via coordinative and ionic
      molecular convolution to provide catalytic membrane-installed microdevices, which
      were applied to the instantaneous allylic arylation reaction of allylic esters
      and aryl boron reagents under microflow conditions to afford the corresponding
      coupling products within 1 second of residence time.

PMID- 19753369
TI  - Convenient modular method for affinity labeling (MoAL method) based on a
      catalytic amidation.
AB  - A modular methodology for affinity labeling, in which three essential elements
      generally constituting affinity probes are prepared separately as individual
      molecules, has been developed based on a catalytic amidation.

PMID- 19753370
TI  - Terphenyl crowns: a new family of receptors containing ethereal canopies that
      direct potassium cation onto benzenoid platforms for cation-pi interactions.
AB  - We have synthesized three simple and versatile terphenyl crowns (TC) receptors
      containing ethereal canopies that direct a potassium cation for efficient cation
      pi interactions as established by 1H NMR spectroscopy and by isolation and X-ray
      crystallography of their K+ salts.

PMID- 19753371
TI  - Pronounced effects of substituents on the iridium-catalyzed borylation of aryl C
      H bonds.
AB  - Iridium trisboryl complexes containing bisphosphine and bipyridine ligands and
      pinacolate and catecholate substituents on boron are reported. A large difference
      in reactivity towards the borylation of C-H bonds is observed for this series of
      trisboryl complexes, and this difference is attributed to the electron-donating
      properties of the pinacolate vs. catecholate groups, and the steric and
      electronic properties of bipyridine vs. bisphosphine ligands.

PMID- 19753372
TI  - Observation of reaction intermediates and kinetic mistakes in a remarkably slow
      self-assembly reaction.
AB  - Several intermediates and oligomeric mistakes in a metal-ligand self-assembly
      reaction are identified by 1H NMR, MALDI-MS, and XRD, providing evidence in
      support of multiple pathways in the "free-for-all" self-assembly process.

PMID- 19753373
TI  - Electrical visualization of chemo-mechanical signal transduction using a smart
      gel-modified gate field effect transistor.
AB  - A field effect transistor (FET) whose gate surface has been modified with a
      stimuli-responsive "smart" polymer gel can visualize the kinetics of the chemo
      mechanical signal transduction as a mode of its altered electrical
      characteristics without any labels.

PMID- 19753374
TI  - Barriers to enantiocontrol in Lewis acid catalyzed hetero-Diels-Alder reactions.
AB  - Lewis bases, including reactant aldehydes, inhibit the rate of conversion for
      cycloaddition and those, like aldehydes or nitriles, cause a decrease in
      enantiocontrol due to the Lewis acidity of the activated complex.

PMID- 19753375
TI  - High temperature zincation of functionalized aromatics and heteroaromatics using
      TMPZnCl.LiCl and microwave irradiation.
AB  - A wide range of functional aryl and heteroaryl zinc reagents have been
      efficiently prepared via regio- and chemoselective zincation using TMPZnCl.LiCl
      and microwave irradiation. Sensitive functional groups like esters are compatible
      with the high temperatures of the reactions. The resulting zinc species undergo a
      number of subsequent reactions, providing highly functionalized aromatics and
      heteroaromatics in high yields.

PMID- 19753376
TI  - Electrocyclization of cis-dienals in organic synthesis: a new and versatile
      synthetic method for the preparation of aryl- and heteroaryl-fused coumarins.
AB  - Benzo-, furo-, thieno-, and pyrido[f]coumarins were prepared by generating the 2H
      pyran-2-one moieties from the oxidation of the corresponding 2H-pyran rings,
      which were formed in situ from the electrocyclization of cis-dienals.

PMID- 19753377
TI  - Discrimination of cryptochirality in chiral isotactic polystyrene by asymmetric
      autocatalysis.
AB  - Chiral isotactic polystyrenes induce the enantioselective addition of
      diisopropylzinc to pyrimidine-5-carbaldehyde, affording the enantiomerically
      enriched pyrimidyl alkanol with the corresponding absolute configuration to that
      of cryptochiral polystyrenes in conjunction with asymmetric autocatalysis.

PMID- 19753378
TI  - A dicopper complex chemiluminescence probe for the determination of thiols in the
      extracts of murine P388 lymphocytic leukemia cell.
AB  - A chemiluminescence (CL) probe of peroxidase-like dicopper complex (Cu2L2) for
      the determination of glutathione (GSH) and related cellular thiols was developed
      for the first time.

PMID- 19753379
TI  - Control and modulation of chirality for azobenzene-substituted polydiacetylene LB
      films with circularly polarized light.
AB  - Herein, photo-controlled rearrangement of the azobenzene chromophore in the side
      chains was used to realize enantioselective polymerization and light-triggered
      reversible switching between opposite chirality for the PDA backbone.

PMID- 19753380
TI  - Nondestructive luminescence intensity readout of a photochromic lanthanide(III)
      complex.
AB  - A photochromic Eu(III) complex was synthesized and its emission intensity change
      could be readout using wavelength-divided luminescence modulation.

PMID- 19753381
TI  - An ultrasensitive electrochemical "turn-on" label-free biosensor for Hg2+with
      AuNP-functionalized reporter DNA as a signal amplifier.
AB  - A highly selective electrochemical biosensor for the ultrasensitive detection of
      Hg2+ in aqueous solution has been developed based on the strong and specific
      binding of Hg2+ by two DNA thymine bases (T-Hg2+-T) and the use of AuNP
      functionalized reporter DNA to achieve signal amplification.

PMID- 19753382
TI  - First hexanuclear copper(II) pyrophosphate through hydrolysis of phosphodiester
      with a dicopper complex.
AB  - Facile hydrolysis of a phosphodiester promoted by a dicopper bis(mu-hydroxo)
      complex containing a new biphenyl appended N-bidentate ligand led to the
      isolation of the first example of hexameric copper pyrophosphate through 'in situ
      self assembly'.

PMID- 19753383
TI  - Ionic nano-convection in anodisation of aluminium plate.
AB  - An ionic nano-convection model has been established for elucidating early stage
      anodisation of aluminium plate and the direct consequence of such convection is
      an ordered pattern of charge distribution near the oxide/electrolyte interface,
      guiding the initial ordering of the pore formation.

PMID- 19753386
TI  - A comparison in academic performance between distance and on-campus students in
      allied healthcare education.
AB  - The primary purpose of this study was to examine the differences in background
      characteristics and academic performance of students in distance learning and on
      campus programs in allied healthcare education at one medical university in the
      Eastern United States. The study depended on data from 252 students, drawn from
      three disciplines, clinical laboratory science, health information
      administration, and nuclear medicine. The study employed the chi-square test and
      t-test for analyzing the data. The study's findings suggested no significant
      differences in terms of the background characteristics of gender and previous
      academic performance between distance and on-campus students. However, the two
      groups of students differed significantly in terms of their age composition such
      that, as expected, distance learning students comprised the majority of older
      students (25 years and older) relative to their on campus counterparts. The study
      further showed that, when assessed in terms of their final grade point averages
      as well as certification pass rates, distance and on campus students were
      indistinguishable from each other. Similar results were found when final GPA
      scores within the three separate disciplines were compared and in certification
      scores in two out of the three disciplines. However, the certification scores of
      nuclear medicine technology students were found to be significantly different
      between the two groups, in which on-campus students earned a significantly higher
      score than their counterparts in the distance learning program. Administrators
      and educators who are considering offering distance learning as a method of
      degree obtainment in allied healthcare education need data, such as reported in
      this study, when determining if distance learning can be as effective as on
      campus learning in allied healthcare education.

PMID- 19753387
TI  - Comparison of online and traditional ethics education: a pilot study.
AB  - INTRODUCTION: This research note describes a pilot study that tested the
      feasibility measures for ascertaining whether students in an online ethics course
      learn as much as, less than, or more than students enrolled in a traditional
      (classroom) ethics course. METHODS: Participating students in both the online and
      traditional courses completed a Technology Survey to measure possible group
      differences in terms of their familiarity and comfort level with using a
      computer, and a Richness of Experience Survey to garner their perceptions of the
      learning environment of the course. Students' academic performance in the two
      classes were also compared. RESULTS: The Technology Survey revealed no
      statistically significant differences between the two groups at the .05 level on
      any of the items, with the exception of the item about the convenience of
      attending class. The groups did not differ in terms of their performance on any
      of the academic performance criteria, although the descriptive data were
      suggestive. Finally, the data from the Richness of Experience Survey also showed
      no distinction between the groups. CONCLUSION: Because the number of participants
      is very small, this analysis had low power. The descriptive data presented
      indicate that further research into differences on the essay portion of the exam
      may be warranted.

PMID- 19753388
TI  - A pilot study to identify developmental delay in children in underserved urban
      community child care settings.
AB  - Children in underserved community child care were examined to determine the
      frequency of and a method to identify developmental delay. Initially, during
      daily experiential observations, child care providers at four urban community
      centers identified children with or at-risk-for developmental delay. Through the
      administration of the Denver II screening tool the project directors, an
      occupational therapist and a physical therapist, confirmed or rejected child care
      providers' concerns. The frequency of developmental concerns in this sample of 95
      children was higher than reported in the general population. The reliability
      between child care providers' at-risk identification of children and therapists'
      "Suspect" results of children on the Denver II was remarkably high. This pilot
      study examines a method that can be implemented in community settings to support
      the early identification of children with possible developmental delay and to
      increase access to early intervention and early childhood services.

PMID- 19753389
TI  - From scholarly teaching to the scholarship of teaching: a retrospective look at
      strategies that foster the transition of scholarly work in allied health into
      credible forms of scholarship.
AB  - With heavy teaching loads and service expectations, many allied health faculty
      members find themselves in situations that limit their ability to engage in
      traditional research and scholarship of sufficient magnitude to meet
      institutional standards for promotion and tenure. Strategies that link teaching
      or service activities to scholarly productivity increase the potential for allied
      health faculty to build credible forms of scholarship and find their niche in the
      academy. To explore the viability of the scholarship of teaching in allied
      health, we reflect on the experience of a small group of allied health faculty
      members when they chose to engage in the process of transforming the scholarly
      teaching embedded in the design, implementation, and evaluation of an allied
      health project grant (AGElink grant) into the scholarship of teaching. Through
      retrospective reflection, we aim to clarify the strategies that emerged in the
      process and propose ways in which faculty members may implement such strategies
      in their teaching to further their career development.

PMID- 19753390
TI  - Building interdisciplinary teamwork among allied health students through live
      clinical case simulations.
AB  - A limited, yet growing, body of research suggests that health care students
      educated in interdisciplinary teamwork may become more collaborative
      professionals in the workplace, which, in turn, may foster more productive and
      satisfied health care professionals. Researchers also have identified lower
      mortality and morbidity rates, fewer hospitalizations, decreased costs, and
      improved function by patients among significant health benefits of
      interdisciplinary teamwork, especially when it is applied to underserved and
      geriatric populations. Such positive outcomes have prompted medical schools and
      accreditation boards of many allied health professions to add interdisciplinary
      education into their training requirements. Meeting these requirements has
      challenged universities, where there are multiple allied health programs and
      limited time, faculty, and financial resources to coordinate interdisciplinary
      education. The challenges have been magnified by insufficient research on the
      most effective methods to educate university students about interdisciplinary
      teamwork. This article presents the background, evolution, and key building
      blocks of one such method: a simulation-based workshop designed at our university
      over 7 years to educate its allied health students about various health
      professions through shared learning, interaction, and collaboration.

PMID- 19753391
TI  - Issues, and the questions they inspire, when one considers the development of
      European higher education for health care professionals.
AB  - This paper highlights various aspects of an emerging European health strategy and
      the potential consequences this may bring. The various directives of the European
      Commission, ratified by the European Parliament and each of the Parliaments of
      the member states, are gently and progressively forging integration of systems
      and processes. These systems and processes are concerned with governance and
      regulation and are aimed at establishing equivalence and standards of activity
      across the Union. The European Union is not a federated state. However, in order
      for it to work effectively as a trading block, the establishment of these
      standards into social, educational and new health care processes is seen as
      essential. Therefore, various directives from the European Commission are being
      laundered to expedite this. These directives are often opposed by the member
      states and the ensuring debate generates many talking points. This paper raises
      some of these talking points in the area of Higher Education and health care
      strategy. The conclusion of the paper suggests what further debate needs to occur
      within the European Union if integration is to succeed.

PMID- 19753392
TI  - Student criminal background checks in colleges of allied health.
AB  - The demand that criminal background checks be performed for students in allied
      health schools and programs has soared in recent years. The need for criminal
      background checks on students entering the health care professions has emerged as
      a critical issue largely due to requirements by clinical affiliate training
      sites. The Joint Commission published a standard stating, "for staff, students
      and volunteers who work in the same capacity as staff who provide care,
      treatment, and services, at Elements of Performance 5 states criminal background
      checks are verified when required by law and regulation and organization policy."
      More simply stated, this means that criminal background check records must be
      verifiable if required by some authoritative entity such as state law. However,
      whether by misinterpretation of the standard or through conscious decision by
      organization policy makers, many health care organizations suddenly began to
      require criminal background checks as part of their affiliation agreements with
      health related schools or programs. The focus of this study was to identify
      current practices of allied health institutions regarding their conduct of
      criminal background checks on students entering the allied health professions.

PMID- 19753393
TI  - The socialization of dietetic students: influence of the preceptor role.
AB  - This paper describes the influence of the preceptor on the evolving professional
      socialization of dietetic students. The study was conducted with Canadian
      dietetic students and interns and was designed to explore factors causing student
      stress. Students were asked to identify a series of common potentially stressful
      situations, to comment on what it is like to be a student today and to identify
      changes that preceptors had made that helped them reduce the stress in their
      lives. Data analysis was initially conducted using a thematic analysis, followed
      by a more indepth analysis informed by hermenutics and social role theory. A
      total of 284 dietetic interns and students responded to the web-based survey.
      Initial analysis of the data revealed six recurrent themes underlying student
      stress however, further analysis revealed the essential theme of a "power over"
      hierarchical learning environment. This environment was demonstrated in several
      ways: withholding information, undermining confidence and inaccurately assessing
      competence. Results highlight the importance of formal training for preceptors to
      help them develop the mentoring skills required to be professional role models.

PMID- 19753394
TI  - Exploring professional-related outcome differences between phlebotomy
      technicians, medical laboratory technicians, and medical technologists.
AB  - As part of a large scale practice analysis on Phlebotomy Technicians (PBTs),
      Medical Laboratory Technicians (MLTs), and Medical Technologists (MTs),
      additional data on four "home made measures" of professional-related outcomes,
      i.e., professional development, quality assurance monitoring, employer
      reimbursement, and types of continuing education, were also collected. In order
      to maximize data use from the overall sample of 3,097 respondents (constituting
      only 18% of the population surveyed), pairwise deletion of data was utilized. No
      a priori differences between PBTs, MLTs and MTs on these outcomes were
      hypothesized, and none were found for professional development and employer
      reimbursement. The finding that PBTs were lower than MLTs and MTs on quality
      assurance monitoring was interpreted as being job expected. Despite the study
      limitations, professional development for not just laboratory professionals but
      all allied health professionals remains an important recruitment and retention
      issue, as demand for all health services is expected to increase.

PMID- 19753395
TI  - Reflective electronic portfolios: a design process for integrating liberal and
      professional studies and experiential education.
AB  - The purpose of this article is to describe the process used to create and pilot
      test a customized reflective electronic portfolio (e-portfolio) that integrates
      learning across three distinct components of an entry-level 6.5 year Doctor of
      Physical Therapy (DPT) program. During the 2004-2005 academic year, a pilot test
      was conducted with 10 students, representative of all 6.5 years in the DPT
      program. Development of our reflective e-portfolio model consisted of four
      stages: design a paper-based portfolio model to organize and create linkages
      among the liberal studies, professional, and experiential components of a DPT
      program; transform the model into an electronic format; create a demonstration e
      portfolio tutorial; and evaluate the e-portfolio model via pilot testing. An
      interdepartmental team of faculty from physical therapy (PT), cooperative
      education, educational technology, and two PT students developed the e-portfolio
      model to map, visualize, and create linkages for student learning. Input to
      assist with the model design process was gathered from PT faculty and students
      through three focus groups. Data were collected on student experiences with the e
      portfolio through written surveys at three points during the project and through
      face-to-face discussion. Written reflection, integral to the model, required
      students to reflect on artifacts selected from existing academic and experiential
      materials. Our project resulted in the generation of a reflective e-portfolio and
      tutorial customized for DPT students. Evaluation by users indicated that the
      reflective e-portfolio helped them organize and integrate academic and
      experiential learning and illuminate developmental transitions. Further research
      with a larger sample is indicated to examine the impact of e-portfolios on
      student learning and professional development.

PMID- 19753396
TI  - Use of a clinical seminar to horizontally integrate basic science and clinical
      topics for year-one students.
AB  - OBJECTIVE: To describe a clinical seminar introduced to integrate basic science
      and clinical topics for first-quarter chiropractic students. METHODS: A 2-hour
      interactive seminar was created to integrate information from a diverse array of
      basic science and clinical courses that students undertake during the first
      quarter of a chiropractic degree program. A patient from teaching clinic served
      as the clinical focus for integrating basic science and clinical topics. Student
      knowledge, confidence in knowledge and perceptions of the program were assessed
      using blinded questionnaires. Changes in student knowledge were analyzed using
      the sign test. Changes in student confidence in knowledge were assessed using the
      Wilcoxon Signed Rank test for two related samples. Student perceptions of the
      experience were assessed using six Likert items and written comments that were
      analyzed qualitatively. RESULTS: One hundred ten students participated in the
      seminar. A statistically significant improvement in student knowledge and
      confidence in knowledge was observed immediately following the seminar. Student
      satisfaction with the program was considered high, based on questionnaire scores.
      CONCLUSION: Overall, attendance at the seminar enhanced student clinical and
      basic science knowledge and confidence in knowledge gained. Students found the
      seminar enjoyable, and the seminar achieved the goal of integrating clinical
      information with basic science information.

PMID- 19753397
TI  - A comparative evaluation of teaching methods in an introductory neuroscience
      course for physical therapy students.
AB  - BACKGROUND: The use of computer-based instruction (CBI) in physical therapy
      education is growing, but its effectiveness compared to lecture is undefined.
      This study compared CBI to lecture in an introductory neuroscience course for
      students in their first year of a 3 year professional program leading to the
      Doctor of Physical Therapy Degree. SUBJECTS: Twenty-eight students participated
      in 2003 and 34 in 2004. METHODS: A randomized, cross-over design was employed.
      The course was divided into two sections with an exam after each. Students in one
      group participated in CBI during the first half of the course and lecture during
      the second half with the order of participation reversed for the other group. A 6
      months post-course review exam was also administered. Exam scores, study time,
      and student opinions regarding teaching methods were collected after each half of
      the course. Course development costs for both teaching approaches were also
      documented. RESULTS: There were no statistically significant differences in exam
      scores between participant groups. CBI students spent less time studying. Student
      did not distinguish a major preference for either instruction method. Many
      students preferred that CBI be used as a complementary rather than mutually
      exclusive instructional method. Lecture-based instruction was much less expensive
      than CBI. CONCLUSION: Lecture-based instruction was more cost effective than CBI,
      but CBI was more time efficient in terms of student learning.

PMID- 19753398
TI  - Exploring the cultural adaptability of doctoral entry-level physical therapist
      students during clinical education experiences.
AB  - Cultural competence is an essential component of health care education. The aim
      of this study was to explore the development of cultural competence in 14
      physical therapist students during their final, 23 weeks of clinical education
      (CE) experiences. A mixed methods design was used to quantitatively measure and
      qualitatively describe cultural adaptability as an indicator of cultural
      competence. Subjects completed the Cross-Cultural Adaptability Inventory (CCAI)
      at the end of their didactic curriculum and again at the end of their CE
      experiences. Constant comparative methods were used to analyze written narrative
      summaries of how students made meaning of their cultural encounters. The students
      exhibited statistically significant changes in the total CCAI score (paired t
      test: p < 0.001), and three CCAI subscales: emotional resilience (paired t-test:
      p < 0.002), flexibility/openness (paired t-test: p < 0.003), and perceptual
      acuity (paired t-test: p < 0.001). There was not a statistically significant
      change in the fourth CCAI subscale, personal autonomy. Qualitatively, four themes
      emerged that described students' cultural encounters with patients, families, and
      co-workers: recognizing cultural descriptors; consideration of feelings, values,
      attitudes and beliefs; effective communication to breakdown barriers; and
      awareness of strategies for current and future cross-cultural practice. Clinical
      cultural encounters are important in the progression toward cultural competence
      in physical therapist students. Changes in attitude appear to be key in effective
      cultural encounters as students learn to communicate and connect with anyone
      perceived to be different from them.

PMID- 19753399
TI  - Processes in the development of international specialist competencies and
      standards: the Sports Physiotherapy for All Project.
AB  - In a world of rapidly developing knowledge it is important that professions
      describe their roles and capabilities. The need for a thorough description of
      sports physiotherapy was addressed through collaboration between the
      International Federation of Sports Physiotherapy (IFSP) and five European higher
      education institutions. This resulted in the Sports Physiotherapy for All
      Project, which has been successful in developing internationally accepted
      competencies and standards for sports physiotherapists. This article describes
      and reflects on the process to communicate useful lessons. METHODS: A competency
      model was chosen to facilitate differentiation and communication of aspects of
      sports physiotherapy practice. Documentation relating to sports physiotherapy
      practice was collected from 16 countries and analysed thematically. A cut and
      paste method was used by a panel of experts to allocate themes to areas of
      practice within the competency model. Theme groups were used to select areas of
      practice for description in competency form. Standards were derived from
      competencies following in depth discussion with the expert panel, and
      triangulation with themes derived from international documentation. RESULTS: A
      rigorous process of international review and revision led to the final list of 11
      competencies and related standards, both accepted by the IFSP. IMPLICATIONS: This
      work provides a foundation for the development of an audit toolkit to guide
      demonstration and evaluation of competencies and standards. This provides a
      foundation for targeted career development activities, appropriate provision of
      training opportunities, and quality enhancement. The experiences gained during
      this project can inform other health professions and their specialisms when
      embarking on a similar journey.

PMID- 19753400
TI  - Evaluation of the perception of cultural competency assessment instrument for
      allied health students.
AB  - BACKGROUND: A growing effort is aimed at reducing health disparities influenced
      by culturally based misinterpretations between patients and health professionals.
      There are few validated instruments to assess students' self-efficacy of cultural
      understandings that are linked to pre and post testing of educational
      interventions. PURPOSE: To evaluate the psychometric properties of an instrument
      that measures perception of self-efficacy with respect to cultural competency in
      allied health students. METHODS: The Perception of Cultural Competency Assessment
      (POCCA) was developed and subsequently evaluated for reliability and validity in
      a convenience sample of 135 students of allied health programs. RESULTS: The
      POCCA demonstrated acceptable internal consistency (a = .92) and 2-week test
      retest reliability of (R = .78). Four sub-scales were identified by factor
      analysis that accounted for 63% of total variance. The subscale a coefficients
      ranged from .61 to .89, and inter-item correlations varied from (R = .41-53).
      POCCA total scores following an educational intervention were significantly
      higher compared to pre-test values (p<.00001). DISCUSSION: While these findings
      provide support for POCCA, more refinement is warranted. The challenge remains to
      improve the test-retest reliability and to expand the sample to evaluate its
      effectiveness in a broader context.

PMID- 19753401
TI  - Effect of an undergraduate elective course, cultural diversity in communication,
      on attitudes and behaviors of communication sciences and disorders students: a
      pilot study.
AB  - The purpose of this pilot study was to examine the effects of the undergraduate
      course, Cultural Diversity in Communication, on attitudes and behaviors of
      undergraduate students in communication sciences and disorders. Pre/post survey
      data were collected during spring semesters 2005/2006, from 24 white participants
      (23 female, 1 male) through the Adapted Spiritual Involvement Scale. The surveys
      assessed attitudes and behaviors related to cultural issues including
      discrimination, white privilege, and interaction with and knowledge about
      differing cultures. By the end of the course, it was found that student attitudes
      improved significantly across 8 of the 14 areas assessed, with the most notable
      gains found for the recognition of white privilege.

PMID- 19753402
TI  - Student service learning and dementia: bridging classroom and clinical
      experiences.
AB  - University students in speech-language pathology and nursing were involved in a
      community service learning project with residents of a long-term care facility
      who had dementia. Nursing students were asked to interact and converse with
      residents to the best of their ability (control group, n = 28). Speech-language
      pathology students were instructed to design a personalized, multi-modality
      "connection kit" for residents based on the tenets of cognitive linguistic
      stimulation and facilitative styles of interaction, which were included within
      course content (experimental group, n = 25). Post-project surveys were
      administered in an attempt to answer the following research question: Do students
      perceive benefits from participating in a service learning project involving long
      term care residents with dementia? Results revealed that the experimental/trained
      group of speech-language pathology students reported greater academic and
      clinical benefits compared to the control group of nursing students. Overall
      implications were that students benefited from a service learning project,
      especially when explicit instruction was provided.

PMID- 19753403
TI  - Knowledge of stroke risk factors and early warning signs of stroke among students
      enrolled in allied health programs: a pilot study.
AB  - BACKGROUND: The inclusion of stroke education modules early in medical school
      curricula has resulted in improved stroke knowledge in graduate physicians. The
      success of these programs suggests that allied health professions programs should
      also consider strategies to improve stroke knowledge in students preparing for
      allied health careers that also require knowledge of stroke risk factors and
      early warning signs. Currently, little is known about stroke knowledge in
      students enrolled in allied health professions programs. METHODS: 208 first- and
      second-year students enrolled in allied health programs completed a survey of
      stroke risk factors and early warning signs of stroke. RESULTS: Risk factor
      knowledge - 99% identified smoking as a risk factor; 67% identified diabetes; 93%
      identified high cholesterol; 89% identified age; and 92% identified physical
      inactivity. Less than 50% of the students identified all 5 risk factors. There
      were no differences between first- and second-year students in risk factor
      knowledge. Early warning signs and first response knowledge - 89% recognized
      sudden confusion or trouble speaking; 94% recognized sudden facial, arm, or leg
      weakness; 65% recognized sudden vision loss; 82% recognized sudden trouble
      walking; and 73% recognized sudden headache as early warning signs of stroke.
      Eighty-one percent recognized calling 9-1-1 as the appropriate first action.
      However, only 25% recognized all five early warning signs and only 20% recognized
      all five early warning signs and would call 9-1-1 as the first action. There were
      differences between first- and second-year students in recognizing 3 of 5 early
      warning signs and appropriate first action to call 9-1-1. CONCLUSIONS: Most
      students recognized individual stroke risk factors and early warning signs but
      few recognized multiple risk factors and early warning signs of stroke.

PMID- 19753404
TI  - The design and evaluation of an interprofessional elective course with a cultural
      competence component.
AB  - Faculty from the Colleges of Nursing, Pharmacy, Social Work and Allied Health
      Sciences at the University of Cincinnati collaborated to create an elective
      course that focused on providing students the opportunity for interprofessional
      education (IPE) and cultural competence training. The course was designed around
      the educational principles described in the literature as most effective for IPE:
      interpersonal and small-group skills, face-to-face interaction, positive
      interdependence, individual accountability and group processing. Impact of the
      course was assessed using two questionnaires focusing on interdisciplinary
      interactions and cultural competence, respectively. The Student Attitude
      Questionnaire (SAQ) and Inventory for Assessing The Process of Cultural
      Competence Among Health Care Professionals-Revised (IAPCC-R) were administered to
      students prior to the start of the course and at the end of the course. The SAQ
      results indicated that students perceived the course to be beneficial in the
      following areas: interprofessional team work, professionalism, self-confidence,
      communication skills, and improved understanding of the roles of health
      professionals and the impact of each profession on patient care. The course also
      promoted students' progress on their personal and professional journeys toward
      cultural proficiency as noted by changes in their pre//post-course IAPCC-R
      scores. Students moved from being culturally aware to becoming culturally
      competent. The design and evaluation of this class can be used as a model by
      other universities to promote interdisciplinary team skills in health professions
      students and to provide additional opportunities for cultural competence
      training.

PMID- 19753405
TI  - Conformists or dynamic professionals: what's the current image that students are
      identifying with as a result of English Allied Health Professional Higher
      Education programmes?
AB  - How Allied Health Professional (AHP) students and educational providers within
      England are redefining professionalism is the focus of this small scale case
      study. A single case study design was used to explore how AHP students viewed how
      they had learnt to be professional. A literature review highlighted that
      professional socialisation and professional knowledge were both aspects of
      professionalism that individual health professionals adhere to, however how
      English based AHPs have benefited from becoming regulated by one professional
      body (Health Professions Council, HPC) is a fundamental question asked by the
      researcher, as there has been a drive both within the educational arena and
      health institutions for interprofessional and generic working. Seven students at
      one London University, where they experienced interprofessional education (IPE),
      were engaged in semi-structured interviews and the researcher used a
      phenomenological approach to interpret the data. The findings showed that all the
      students defined professionalism in terms of generic skills associated with
      patient/client-centred care. This mainly conformed to what they were being
      taught, though they did not feel that IPE enhanced their learning. The students
      felt it was important to have an up to date knowledge base, but thought that some
      of the theory taught was not relevant to their practice. The study concludes that
      there needs to be greater collaboration between higher educational establishments
      and clinical partners to ensure students are given a relevant and consistent view
      of professionalism, which enhances not only their collaborative practice but also
      their independent professional integrity.

PMID- 19753406
TI  - A description of the outcomes, frequency, duration, and intensity of
      occupational, physical, and speech therapy in inpatient stroke rehabilitation.
AB  - PURPOSE: The purpose of this study was to describe the outcomes, frequency,
      duration, intensity, and the specific types of therapeutic intervention of
      inpatient stroke rehabilitation specific to one hospital in the upper midwestern
      region of the United States following implementation of the IRF PPS. DESIGN: This
      was a non-experimental retrospective chart review of individuals who received
      inpatient stroke rehabilitation from January 2003 to June 2004. METHODS: A total
      of 80 medical records met inclusion and exclusion criteria. Data were collected
      on patient and clinical characteristics, FIM scores, LOS, and discharge location
      as well as the intensity, frequency, and total number of occupational therapy
      (OT), physical therapy (PT), and speech therapy (ST) treatment sessions, the type
      of therapy sessions provided, and the type of therapy service providers. RESULTS:
      LOS was 15.19 days +/- 11.69. There was a significant difference (t =-12.163; p =
      .000) between FIM total admission score (71.90 +/- 21.47) and FIM total discharge
      score (92.23 +/- 24.43) ). There was a significant difference in FIM discharge
      scores (F = 26.494; p = 000) based on discharge location with differences found
      between the discharge locations of home and skilled nursing facilities (p = .000)
      and skilled nursing facilities and assisted living facilities (p = .019). Mean
      number of therapy sessions per subject was 21.73 +/- 18.11 for OT, 21.99 +/-
      18.10 for PT, and 18.86 +/- 18.71 for ST. Mean number of sessions per day was
      1.72 +/- 0.31 sessions for OT, 1.65 +/- 0.36 sessions for PT, and 1.52 +/- 0.48
      for ST. Mean number of minutes provided per session was 29.87 +/- 1.77 minutes
      for OT, 29.70 +/- 1.65 minutes for PT, and 27.23 +/- 6.64 minutes for ST. Mean
      intensity (days of therapy/length of stay) was 0.82 +/- 0.13 for OT, 0.85 +/-
      0.13 for PT and 0.70 +/- 0.24 for ST. Of the total OT sessions, 97.41% were
      conducted by the OT and 77.68% were intervention only. Of the total PT sessions,
      65.66% were conducted by the PT, 15.35% were by the PTA, and 92.67% were for
      intervention only. CONCLUSIONS: These findings suggested inpatient stroke
      rehabilitation has an impact on the rehabilitation process as evidenced by the
      improved FIM scores at discharge. Individuals who received inpatient
      rehabilitation for stroke at this facility stayed just over 2 weeks and improved
      on average by 20 points on the FIM. The patients in this study were seen for
      skilled OT, PT, and ST for about 30 minutes per session, 1.5 times per day, and
      received therapy services for 5 to 6 days per week on average. Future prospective
      research investigating the specific types of therapeutic interventions provided
      by each rehabilitation discipline is warranted in order to gain a clearer
      understanding of the effectiveness of inpatient stroke rehabilitation.

PMID- 19753407
TI  - The effectiveness of blended learning environments for the delivery of
      respiratory care education.
AB  - INTRODUCTION: The undergraduate health professions student of the 21st century is
      very technology literate. In an attempt to provide these students with a forum to
      enhance learning, some educators have opted to integrate additional course
      materials via Internet classrooms while still maintaining the face-to-face
      interaction between instructor and learner. METHODS: A retrospective analysis was
      performed with the student course evaluations and demographics of two groups of
      respiratory therapy students (one group participated a traditional learning
      environment and one group participated in a blended learning environment) in a
      baccalaureate degree program. The author employed SPSS quantitative data analysis
      software to conduct statistical analysis. RESULTS: None of the studied variables
      showed a statistically significant difference (p =0.05). Further testing revealed
      an expected positive relationship between pre-existing GPA and the final
      examination grade as well as the final examination grade and the course grade (p
      = 0.05). No other positive relationships were noted. DISCUSSION: The qualitative
      analysis implies a difference in satisfaction between cohorts; however, the
      quantitative analysis of the student evaluations does not provide statistically
      significant differences for any aspect surveyed in the anonymous standardized
      questionnaire. CONCLUSION: The results of this pilot study favor the continuing
      practice of blended learning environments as a viable option for course delivery
      in health care education. The author recommends further study to explore this
      topic in depth with larger cohorts.

PMID- 19753408
TI  - Hands on learning: the use of simulated clients in intervention cases.
AB  - Standardized patients assist with the education of medical, physical therapy and
      nursing students. However, the literature does not discuss the use of these
      learning experiences with occupational therapy students. This article describes
      the use of standardized clients in a simulation learning experiences and the
      responses of occupational therapy students to the instructional modality.
      Qualitative data was analyzed and resulted in the following themes: "I felt like
      a therapist," "I integrated knowledge and applied my skills with the help of my
      partner," and "The experience could be enhanced." On a survey, students rated the
      live simulated learning experience higher than all other instructional methods
      presented. Included are recommendations for structuring activities using
      simulated clients and future research.

PMID- 19753409
TI  - Interdisciplinary learning experience: two years of experience with an
      interdisciplinary learning engagement for physical therapy and special education
      students.
AB  - This article describes two cohorts of students who participated in an
      interdisciplinary learning experience in which physical therapy (PT) and special
      education (SE) pre-professionals collaborated weekly during an eight week fitness
      program for children and youth with disabilities. Forty-one children with
      disabilities and ranging in age from five to 20 years, participated in the
      fitness program. One short term outcome achieved for PT and SE students was
      learning to communicate effectively with students from another discipline. In
      addition, PT and SE students successfully planned and implemented a variety of
      age appropriate fitness activities for participants with disabilities, as well as
      motivated and encouraged participants to engage in the activities. Outcomes for
      participants with disabilities included improvements in the sit-up component of
      the Presidential Fitness Test at the conclusion of the fitness program. The
      children and their parents/guardians appreciated the opportunity to engage in
      fitness activities in a non-threatening environment.

PMID- 19753410
TI  - Emergency departments: an emerging context of Australian allied health practice.
AB  - Multi- and interdisciplinary allied health teams are an emerging service in
      Australian Emergency Departments (EDs). Using a literature review, this article
      describes the Australian ED policy and service context, factors affecting ED use,
      allied health roles, practices and impact. The article fills a gap in the
      literature by providing educators, researchers, therapists and managers with an
      overview of key issues to help inform ED service decision-makers, anticipate
      patient and departmental needs and identify areas for education, quality projects
      and research. Issues current in Australia will be relevant to other developed
      countries where the ED demand, particularly by older people with complex and
      chronic conditions is outstripping capacity.

PMID- 19753411
TI  - Online vs classroom instruction: student satisfaction and learning outcomes in an
      undergraduate Allied Health pharmacology course.
AB  - Online instruction is frequently utilized in allied health education yet only a
      small number of controlled comparative studies specifically in healthcare
      education have been published. PURPOSE: The purpose of this study was to compare
      student satisfaction and objective learning outcomes of an undergraduate allied
      health online pharmacology course using streaming media lectures to traditional
      classroom instruction. METHODS: The online (n=47) and classroom (n=177) courses
      for fall 2005 and spring 2006 used the same instructor, notes, text, learning
      objectives, and exams. Student characteristics, learning style preferences, and
      aptitude for distance learning were measured. A statistically reliable, valid
      survey measured student satisfaction with elements of the course, instructor, and
      self-perceived knowledge gains. Learning outcomes were evaluated using withdrawal
      rates and exam scores. RESULTS: Mean satisfaction scores for both courses were
      high, generally >4.0/5.0. Mean scores from the classroom students were
      significantly higher than online students regarding students' ability to share
      ideas, instructor's ability to establish rapport, self-perceived knowledge gains,
      fundamental principles and application of material, and overall excellence of
      course. There were no significant differences in objective exam scores or
      withdrawal rates. CONCLUSION: The online and classroom pharmacology courses had
      similar withdrawal rates and exam scores, indicating similar learning gains.
      Overall, both courses had high student satisfaction ratings in all 43 criteria
      measured. However, students in the online course were less satisfied with 8
      criteria related to student satisfaction with instructor rapport, course
      excellence, peer interaction, and self-perceived knowledge gains.

PMID- 19753412
TI  - A brief survey of awareness of common health conditions, access to health
      services, and utilization of health services in limited-English-proficiency
      Hispanic/Latino adults.
AB  - BACKGROUND: Limited English proficiency (LEP) and other sociodemographic factors
      are believed to impact health knowledge, healthcare access and overall health
      status. However, the role LEP plays in the overall health awareness and receipt
      of healthcare services is not adequately understood. METHODS: We surveyed 60 LEP
      Hispanic/Latino adults to determine their awareness of common health conditions
      in Hispanic/Latino communities and describe their experiences accessing and
      utilizing health services in the Charleston, SC area. RESULTS: Awareness of
      Common Health Conditions: The majority of participants identified alcoholism as
      an important health condition among Hispanic/Latino adults. Other common health
      conditions reported included drug use, diabetes, HIV/AIDS, and cancer. Access to
      Health Services: All of the participants reported problems obtaining needed
      health services in the past. Problems reported were associated with costs,
      insurance and lack of Spanish-speaking service providers. Utilization of Health
      Services: More than 70% of the participants went to the doctor when they were
      sick, but 50% had never had a physical examination. CONCLUSIONS: The LEP
      Hispanic/Latino adults in this survey were generally aware of major health
      related conditions common among Hispanics/Latinos. The presence of LEP did not
      significantly impact awareness of common health conditions in Hispanic/Latino
      communities. Healthcare access and utilization were influenced by a number
      factors associated with the local healthcare system.

PMID- 19753413
TI  - Practitioners' perceptions of the occupational therapy clinical doctorate.
AB  - Six hundred occupational therapy practitioners from seven states responded to
      questions inquiring about the perceptions of the occupational therapy clinical
      doctorate degree, both at the entry-level and post-professional positions. The
      majority of respondents does not approve of moving to the doctorate for entry
      level practice, and are not interested in pursuing the degree personally. The
      most common reasons for the low interest are the respondents' belief that the
      degree will not further their careers, that practitioners cannot afford to stop
      working to pursue another degree, and that they cannot balance work, family, and
      education. The small number of respondents who are interested in the clinical
      doctorate degree want it for personal development and are interested in clinical
      practice specialization.

PMID- 19753414
TI  - Mutual respect in healthcare: assessing cultural competence for the University of
      Utah Interdisciplinary Health Sciences.
AB  - INTRODUCTION: The University initiated an Interdisciplinary Health Sciences
      Students (IHSS) education program, Cultural Competency & Mutual Respect (CCMR),
      for medicine (MED), pharmacy (PHARM), nursing (NSG), physical (PT) and
      occupational therapy (OT). This study assessed CCMR pre/post learning outcomes
      through the Inventory for Assessing the Process of Cultural Competence
      Revised((c)) (IAPCC-R). METHODS: Subjects included: 100 MED, 140 NSG, 36 PT, 11
      OT and 53 PHARM IHSS. IAPCC-R(c) completed by IHSS: 263 Fall, 2003; 48 Spring,
      2004. Controls included 100 MED and 36 PT. Pre/post test scores were calculated.
      Paired analyses performed, comparing overall CC scores and constructs, p < 0.05.
      RESULTS: Overall pre versus post mean scores: 2003: 69.75 and 71.62; 2004: 66.77
      and 71.85. Paired t-test 2003: MED t = -3.1976 P > t = 0.0020; NSG t = 0.5196 P >
      t = 0.6064; PT t = 4.7181 P > t=0.0000; 2004: PHARM t =-3.7861 P > t=0.0006; All
      other t = -1.7392 P > t = 0.1425. Two sample t-test, significant only for post
      module for Hispanic/Asian/other, 77.50, White, Non-Hispanic 70.37. DISCUSSION:
      Results indicate PT, MED, PHARM attained significant scores for constructs:
      Attitudes, Knowledge, and Skills; but not Encounters and Desires. Post-test
      scores indicated progressions approaching CC, however not yet Culturally
      Proficient. CONCLUSION: Results indicate IHSS are becoming more Culturally Aware
      as a result of CCMR participation; however, they have not achieved Cultural
      Proficiency. The constructs of Cultural Desire and Encounters warrant curricular
      enhancement for progression towards Cultural Proficiency.

PMID- 19753415
TI  - Dietitians and exercise physiologists in primary care: lifestyle interventions
      for patients with depression and/or anxiety.
AB  - Mental illness affects one in five Australians in any given year and depression,
      anxiety and substance abuse are the most prevalent of the mental health problems.
      Mental illness is traditionally managed with medication and psychological
      intervention but exercise and diet have also been shown to be related to mental
      illness and are associated with improvements in mental health. The present
      article aims to describe the background and practical issues arising from the
      establishment of diet and exercise assessments and intervention for people
      receiving treatment for depression and anxiety in general practice settings.
      Patients were referred by their general practitioners, and attended sessions
      either in rooms at their practitioner's surgery or at a central clinic location.
      The program involved an initial assessment, four individual consultations with a
      dually qualified dietitian and exercise physiologist, and a final assessment.
      Issues in the process of assessing mental health, diet quality, physical fitness
      and physical activity behaviours are described as are key components of the
      tailored treatment programs. Strategies for improving motivation and adherence
      such as adjusting frequency of sessions, use of homework and means of
      communication are highlighted.

PMID- 19753416
TI  - Interprofessional, practice-driven research: reflections of one "community of
      inquiry" based in acute stroke.
AB  - Research is often scholarship driven and the findings are then channelled into
      the practice community on the assumption that it is utilising an evidence-based
      approach in its service delivery. Because of persisting difficulties in bridging
      the practice-evidence gap in health care, there has been a call for more active
      links between researchers and practitioners. The authors were part of an
      interprofessional research initiative which originated from within an acute
      stroke clinical community. This research initiative aimed to encourage active
      participation of health professionals employed in the clinical setting and active
      collaboration across departments and institutions. On reflection, it appeared
      that in setting up an interprofessional, practice-driven research collaborative,
      achievements included the instigation of a community of inquiry and the affording
      of opportunities for allied health professionals to be actively involved in
      research projects directly related to their clinical setting. Strategies were put
      in place to overcome the challenges faced which included managing a demanding and
      frequently changing workplace, and overcoming differences in professional
      knowledge, skills and expertise. From our experience, we found that
      interprofessional, practice-driven research can encourage allied health
      professionals to bridge the practice-evidence gap, and is a worthwhile experience
      which we would encourage others to consider.

PMID- 19753417
TI  - What attracts students to interprofessional education and other health care
      reform initiatives?
AB  - BACKGROUND: An international consensus has emerged that interprofessional
      education (IPE) and other health care reforms are necessary to address the
      increasing complexity of patients' health needs. Despite overwhelming barriers to
      its system-wide implementation, health professional students worldwide have
      organized themselves to promote IPE and have achieved considerable attention.
      This study seeks to offer insights into what attracts students to IPE and other
      health care reform initiatives and how advocates of change can stimulate this
      interest. METHODS: Using a qualitative research methodology, 69 students
      representing 25 disciplines from 22 institutions across North America were
      interviewed and surveyed on why and how they became interested in IPE. RESULTS:
      Students were attracted to the possibility of enhancing patient care (n=17),
      advancing their careers (n=17) and learning more about the issue (n=15). The
      participating students first became involved in IPE after they joined a student
      organization (n=21), attended an IPE conference (n=10) or received personal
      encouragement to do so from a dean (n=2), instructor (n=3), school administrator
      (n=7) or peer (n=11). These findings point to several strategies that advocates
      can use to capitalize on the potential of student advocacy to gain support for
      IPE and new health care innovations. CONCLUSION: This study is the first of its
      kind to delineate how clinicians, educators, researchers and policymakers can
      attract students to health care reform initiatives. This work can inform the
      strategic efforts of advocates to make the idea of IPE and health care reform
      more attractive to students (as both learners and leaders) and enlist their help
      in achieving it in the future.

PMID- 19753418
TI  - The impact of feeder school selectivity on predicting academic success in an
      allied health professional program.
AB  - Admission committee members have the important task of selecting candidates who
      have the best chance of academic success in their professional programs. Graduate
      record examination (GRE) scores and grade point average (GPA) are typically given
      heavy consideration in the admissions process. The purpose of the present study
      is to assess the impact of feeder school selectivity on the ability of GRE scores
      and GPA to predict probationary status in entry level physical therapy students.
      METHODS: Three hundred five (249 female, 56 male) students, who graduated from an
      entry-level Doctor of Physical Therapy Program between 2001 and 2006, were
      included in this analysis. Feeder school selectivity was defined as either less
      selective/selective or more selective/most selective (US News and World Report
      2005). Unpaired t-tests assessed differences in GRE scores and GPA between the
      less selective/selective and more selective/most selective groups. Receiver
      operating characteristic curve (ROC) analysis assessed the ability of GRE score
      and GPA to predict probationary status. Probation for at least one semester
      (Cumulative GPA <3.0 in the physical therapy program) was considered an event.
      Statistical tests with a p-value <0.05 were considered significant. RESULTS:
      Verbal GRE scores [443.68 (+/-75.16) vs. 489.01 (+/-77.63)], Quantitative GRE
      scores [546.40 (+/-98.70) vs. 610.16 (+/-78.57)] and Total GPA [3.37 (+/-0.32)
      vs. 3.30 (+/-0.31)] were significantly different between the less
      selective/selective group and the more selective/most selective group (p<0.05).
      Math science GPA [3.29 (+/-0.34) vs. 3.19 (+/-0.37)] was not significantly
      different between the less selective/selective and more selective/most selective
      groups (p>0.05). One hundred fourteen of the subjects attended feeder schools
      that were considered less selective/selective. Eighty-four students (28%( were on
      probation for at least one semester. Verbal GRE (ROC curve area: 0.62, p=0.001),
      Quantitative GRE (ROC curve area: 0.71, p<0.001), total GRE (ROC curve area:
      0.69, p<0.001), total GPA (ROC curve area: 0.59, p=0.01) and undergraduate
      program rigor (ROC curve area: .64, p<.001) classification schemes were all
      significant predictors of probation. The optimal threshold values for Verbal GRE,
      Quantitative GRE, total GRE, and total GPA were 455 (sensitivity 61%, specificity
      52%), 575 (sensitivity 69%, specificity 65%), 1025 (sensitivity 67%, specificity
      61%) and 3.25 (sensitivity 64%, specificity 56%) respectively. The optimal
      threshold value for undergraduate rigor was 4 (sensitivity 70%, specificity 56%).
      DISCUSSION: The results of the present study indicate feeder school selectivity,
      GRE scores, and GPA are all independent predictors of probationary status.
      Assessing feeder school selectivity in addition to GREs and GPAs during the
      admissions process may therefore be warranted.

PMID- 19753419
TI  - Characterizing job satisfaction and intent to leave among nationally registered
      emergency medical technicians: an analysis of the 2005 LEADS survey.
AB  - The primary purpose of this study was to characterize job satisfaction with
      opportunities for advancement, job satisfaction with pay and benefits, and intent
      to leave the EMS profession among Nationally Registered EMT-Basics and EMT
      Paramedics. A secondary data analysis was performed on the National Registry of
      EMTs Longitudinal Emergency Medical Technician Attributes and Demographic Study
      Project (LEADS) 2005 core survey. We used chi-square and multiple logistic
      regression analyses to test for differences in job satisfaction with
      opportunities for advancement, job satisfaction with pay and benefits, and intent
      to leave the EMS profession across years of experience and work location. Among
      11 measures of job satisfaction, NREMT-Basics and NREMT-Paramedics were least
      satisfied with opportunities for advancement and pay and benefits (67.8 and
      55.2%, respectively). Nearly 6% of respondents reported intentions of leaving the
      profession within 12 months. In univariate analyses, job satisfaction with
      advancement opportunities varied across years of experience and work location.
      Job satisfaction with pay and benefits varied across years of experience and work
      location. The proportion reporting intentions of leaving the profession did not
      vary across the two independent variables of interest. In multivariable logistic
      regression, statistical differences observed in univariate analyses were
      attenuated to non-significance across all outcome models. Income, personal
      health, level of EMS certification, and type of EMS work were significant in
      several outcome models. EMS workforce research is at its infancy, thus our study
      adds to a limited but growing body of knowledge. In future and replicated
      research, one will need to consider different person and organizational variables
      in predicting different measures of job satisfaction among EMS personnel.

PMID- 19753420
TI  - Interprofessional healthcare: a common taxonomy to assist with understanding.
AB  - Implementation of models of interprofessional healthcare can be a difficult
      process. One of the contributing factors is that different professionals use
      different terminology when addressing the same concepts. This paper proposes a
      common taxonomy for models of interprofessional care in order to facilitate
      understanding of these models regardless of the health professions involved.
      Three basic models are described with specific examples: the Physician Extender
      Model, Triage Model, and Parallel Model.

PMID- 19753421
TI  - The use and perceptions of concept mapping as a learning tool by dietetic
      internship students and preceptors.
AB  - Critical thinking and problem solving skills are currently emphasis areas in the
      education of allied health professionals. Use of concept maps to teach these
      skills have been utilized primarily in nursing and medical education, but little
      has been published about their use in dietetics education. Therefore the purpose
      of this study was to evaluate the potential efficacy of concept mapping as a
      learning tool for nutrition assessment among dietetic interns and its
      acceptability by internship preceptors. Nineteen dietetic interns and 31
      preceptors participated in a quasi-experimental pre-/post-design in which the
      concept mapping strategy was taught as a replacement for the traditional
      nutrition care plan. The pre-concept map mean score was significantly lower than
      the post-concept mean score (28.35 vs. 117.96; p=0.001) based on the Student t
      test, thus indicating improved critical thinking skills as evidenced through
      concept mapping. Overall students' perceptions of concept mapping as a teaching
      learning method were more positive than the preceptors' perceptions. In
      conclusion, internship preceptors and dietetic interns perceived concept mapping
      as effective in assisting interns to engage in critical thinking, to problem
      solve, and understand relationships among medical nutrition therapy concepts.
      However, preceptors had more negative attitudes toward concept mapping than the
      dietetic interns related to time and effort to complete and evaluate the concept
      map.

PMID- 19753422
TI  - Time and the river.

PMID- 19753423
TI  - Analysis of incomes of new graduate physician assistants and gender, 1998-2006.
AB  - The purpose of this study was to determine if there was a gender-based difference
      in starting incomes paid to new graduate physician assistants. Data obtained from
      the American Academy of Physician Assistants (AAPA) Division of Data Services and
      Statistics from 1998 through 2006, utilizing the Annual AAPA Physician Assistant
      Census and the Annual AAPA New PA Student Census, were analyzed using SPSS at an
      alpha level 0.05. A statistically significant difference was found between the
      incomes of male and female new graduates utilizing the t test for independent
      samples in each survey year and all years combined. In addition to gender, over
      150 independent variables were evaluated by backward regression analysis. Gender
      remained statistically significant in all models of each year and all years
      combined. The results of the study indicate that female new graduate physician
      assistants received a lower income than their male counterparts, even when other
      confounders were considered.

PMID- 19753424
TI  - Collaborative model of clinical education in physical and occupational therapy at
      the Mayo Clinic.
AB  - Clinical education experiences, a significant portion of entry-level professional
      education programs in physical therapy (PT) and occupational therapy (OT),
      commonly use a one student to one clinical instructor (1:1) model. Recently,
      though, the collaborative model of clinical education has received more attention
      in the professional literature and in clinical education experiences. The
      collaborative model--where two or more students complete a clinical education
      experience within a specific clinical area while supervised and educated by one
      primary clinical instructor (2:1 or 3:1)--has been used historically within the
      Mayo Clinic's Department of Physical Medicine and Rehabilitation in PT and now
      OT. Clinical instructors, referred to as clinical education coordinators,
      supervise and educate students as a primary job responsibility. Students also
      teach and learn from each other. This article describes the collaborative
      clinical education model used at the Mayo Clinic. Benefits and challenges of the
      model, feedback from students who have participated in the model, and the
      productivity implications of using the model are included.

PMID- 19753425
TI  - Factors that influence the clinical decision-making of rehabilitation
      professionals in long-term care settings.
AB  - The purpose of this qualitative research was to evaluate the reasoning of
      clinicians practicing in long-term care facilities and to explore factors
      influencing their professional development. Eighteen participants were recruited
      from eight clinical sites and included seven occupational therapists, eight
      physical therapists, and three speech therapists distributed across three groups
      relative to experience. Nonparticipant observation and videotape of therapist
      patient interactions were used in semi-structured interviews with each
      participant. Qualitative data analysis software was used during a process of open
      and axial coding, followed by thematic analysis. The facilitory and inhibitory
      factors that affect clinical reasoning and professional development were
      identified. Rehabilitation professionals in long-term care demonstrated clinical
      reasoning within the context of patient-centered goals. Well-developed and
      explicit programs for mentorship, professional development, and continuing
      education fostered their clinical reasoning abilities. Participants perceived
      that these factors were vital to achieving optimal patient outcomes.

PMID- 19753426
TI  - Do occupational therapy and physical therapy curricula teach critical thinking
      skills?
AB  - This study evaluated whether critical thinking ability can be improved through
      participation in occupational therapy (OT) and physical therapy (PT) curricula.
      The researchers compared levels of the critical thinking skills of OT and PT
      students at the beginning and end of their programs to determine whether changes
      occurred and to examine facets of the curricula that may have caused the
      differences. The curricula include teaching strategies of problem-based learning
      modules, small group discussion and problem-solving, case studies, clinical
      observation, and evidence-based practice assignments, as well as teaching about
      critical thinking as a process in itself. Fifty OT and PT students completed the
      Watson-Glaser Critical Thinking Appraisal at the beginning and end of 20 mos of
      the academic phase of their master's degree programs. Researchers analyzed the
      data using a one-way repeated-measures ANOVA. Results showed no differences
      between OT and PT students on the pretest or post-test and no differences for PT
      students between the pretest and post-test. OT students' scores increased
      significantly from pretest to post-test. The influence of the timing of teaching
      critical thinking skills in the resulting differences between the two curricula,
      as well as the validity of the Watson-Glaser Critical Thinking Appraisal is a
      valid measure of critical thinking changes in allied health students are
      discussed.

PMID- 19753427
TI  - Admission criteria and student success in a medical radiation sciences program.
AB  - Determining admission criteria that will predict successful student outcomes is a
      challenging undertaking for newly established health professional programs. This
      study examined data from the students who entered a medical radiation sciences
      program in September 2002. By analyzing the correlation between undergraduate
      GPA, grades in undergraduate science courses, performance in program coursework,
      and post-graduation certification examination results, the authors determined
      admission criteria that were linked to successful student outcomes for
      radiological technology and radiation therapy students.

PMID- 19753428
TI  - Determinants of job satisfaction among radiation therapy faculty.
AB  - Job satisfaction is one of the most significant predictors of employee retention
      in a variety of occupational settings, including health care and education. A
      national survey of radiation therapy educators (n = 90) has indicated that
      respondents are not satisfied with their jobs based on data collected using the
      Minnesota Satisfaction Questionnaire (MSQ). To predict the factors associated
      with job satisfaction or dissatisfaction, the authors used a nine-item
      questionnaire derived from the MSQ. Educators were grouped according to their job
      satisfaction scores, and multiple discriminant analysis was used to determine
      which factors were predictive of satisfaction among groups of educators.
      Statistical results indicate that ability utilization, institutional support,
      compensation, personnel, and job characteristics were key determinants of job
      satisfaction among radiation therapy educators. These results may better inform
      faculty and administration of important factors that can promote job satisfaction
      and retain faculty in radiation therapy education programs.

PMID- 19753429
TI  - S.M.A.R.T. mothers are resisting tobacco: prenatal smoking cessation in WIC
      mothers.
AB  - This article presents outcomes of the Smart Mothers Are Resisting Tobacco
      (S.M.A.R.T. Moms) project, a "5 A's"-based, best-practices intervention for
      prenatal smoking cessation targeting primarily pregnant WIC patients in
      Tennessee. Evidence-based training using "5 A's" materials were provided to
      health care providers. Providers in turn counseled patients on smoking cessation
      and provided individual cessation treatment plans with educational information
      and materials. At the conclusion of the 4-year project, 13,285 patients had
      received counseling and smoking cessation resources through the project. The
      overall success rate for participants who received counseling and agreed to use
      the self-help guide was 24.2% vs 20.9% for those who did not choose to use the
      self-help guide but did receive counseling, exceeding success rates previously
      found in similar settings. The outcomes of this project support research that
      even brief tobacco cessation counseling (5 to 15 min), delivered by trained
      providers and coupled with pregnancy-specific self-help materials, can increase
      cessation rates in women during pregnancy. Outcomes from this project also
      support that, when provided with adequate training and pregnancy-specific self
      help materials, health care providers will more consistently counsel patients on
      smoking cessation during pregnancy.

PMID- 19753430
TI  - Can a four-dimensional model of occupational commitment help to explain intent to
      leave the emergency medical service occupation?
AB  - Using a sample of 854 emergency medical service (EMS) respondents, this study
      supported a four-dimension model of occupational commitment, comprised of
      affective, normative, accumulated costs, and limited alternatives. When personal
      and job-related variables were controlled, general job satisfaction emerged as a
      negative correlate of intent to leave. Controlling for personal, job-related, and
      job satisfaction variables, affective and limited alternatives commitment were
      each significant negative correlates. There were small but significant
      interactive effects among the commitment dimensions in accounting for additional
      intent to leave variance, including a four-way interaction. "High" versus "low"
      cumulative commitment subgroups were created by selecting respondents who were
      equal to or above ("high") versus below ("low") the median on each of the four
      occupational commitment dimensions. A t-test indicated that low cumulative
      commitment EMS respondents were more likely to intend to leave than high
      cumulative commitment EMS respondents.

PMID- 19753431
TI  - [Influenza A (H1N1)swl virus. An inappropriate visit].

PMID- 19753432
TI  - [Long-acting beta2-agonist bronchodilators safety for asthma treatment].

PMID- 19753433
TI  - [Alternative medicine: between the unquestioned enthusiasm and the misinformed
      scepticism].

PMID- 19753434
TI  - [Urinary infection and vesicoureteral reflux: what we need to do].

PMID- 19753436
TI  - [Blood lead levels in children from the city of La Plata, Argentina. Relationship
      with iron deficiency and lead exposure risk factors].
AB  - INTRODUCTION: Environmental exposure to lead and the subsequent poisoning are a
      main public health concern worldwide. Children have a higher vulnerability to
      lead toxic effects, and many reports have shown the association between iron
      deficiency and lead poisoning. In Argentina, reports about lead levels in
      children are scarce. Our aims were to assess blood lead levels in children and
      determining their relationship with iron deficiency and known lead exposure risk
      factors. MATERIAL AND METHODS: We performed a cross-sectional study in a sample
      of 93 children (age range, 6 months to 5 years) receiving care at La Plata
      Children s Hospital. A social and environmental survey was done, and blood lead,
      hemoglobin and ferritin levels were assessed. RESULTS: Geometric mean blood lead
      level was 4.26 microg/dl (95% CI, 3.60-5.03); prevalence of blood lead levels
      >or=10 microg/dl was 10.8%. Higher blood lead levels were found in children
      living in households with lead-handling contaminating activities (6.74 vs. 3.78
      microg/dl; p= 0.005) and in very low-income households (5.68 vs. 3.71 microg/ dl;
      p= 0.020). The presence of blood lead levels >or=10 microg/dl was strongly
      associated with iron deficiency (OR 5.7; 95% CI: 1.34-23.41) and with lead
      handling activities at home (OR 4.8; 95% CI: 1.12-20.16). CONCLUSION: The
      prevalence of blood lead levels >or=10 microg/dl is a matter of concern in the
      population studied. Iron deficiency and development of lead-handling activities
      at home were the risk factors associated with high blood lead levels.

PMID- 19753437
TI  - [Cross-cultural adaptation of the KIDSCREEN questionnaire to measure the health
      related quality of life in the 8 to 18 year-old Argentinean population].
AB  - BACKGROUND: Health related quality of life (HRQOL) measures are increasingly used
      in research and clinical practice. The KIDSCREEN is a questionnaire developed in
      Europe for an 8 to 18 year-old population. OBJECTIVE: To cross-culturally adapt
      this questionnaire for the Argentinean population, and to evaluate its cultural
      adequacy and semantic equivalence against the original version. METHODS: Forward
      and backward translation according to international recommendations for cross
      cultural adaptation of questionnaires, including the translation by professional
      linguists, cognitive interviews with people of different ages, gender and
      socioeconomic status to analyze cultural adequacy, and comparison of the
      Argentinean with the original versions to establish semantic equivalence.
      RESULTS: The language required adaptation in the use of pronouns and verb tenses.
      Most of the items were considered to have low translation difficulty and high
      semantic equivalence. Boys and girls 8-11 years (n= 7), 12-15 years (n= 7), and
      16-18 years (n= 2) participated in the interviews, as well as 6 mothers. There
      were no major difficulties in understanding, but younger children being in the
      lower socioeconomic status had some difficulties to answer the questionnaire.
      Eight questions were modified to achieve greater semantic equivalence.
      CONCLUSIONS: The Argentinean version of the KIDSCREEN questionnaire obtained
      through cross-cultural adaptation process, was equivalent to the European
      version. Future studies should establish its reliability and validity. It
      provides a useful measure of HRQOL for studies in clinical, school or community
      settings, with the possibility to establish international comparisons.

PMID- 19753438
TI  - [Fatty acid composition of human milk from mothers of preterm and full-term
      infants].
AB  - INTRODUCTION: Human milk is an essential food for newborns and affects life in
      the long or short terms. Its composition is modified by nutritional status and
      maternal diet as well as by gestational age of the newborn. It provides human
      milk-fed infants with the medium-chain fatty acids which are a source of energy,
      and essential fatty acids and their metabolic derivatives which have been
      involved in the neural maturation. OBJECTIVES: Due to the fact that there is
      little local data concerning the fatty acid composition in human milk of pre-term
      and full-term newborns, the present study was carried out in women living in the
      urban area of the Buenos Aires Province. MATERIALS AND METHODS: Samples were
      provided by the Bank of Human Milk, H.I.G.A. San Martin Hospital. They
      corresponded to mothers who had delivered preterm infants (28-36 weeks of
      gestational age) or full-term infants (37-42 weeks of gestational ages). Total
      lipids were extracted, and the fatty acid composition was determined by gas
      liquid chromatography. RESULTS: Results showed increases in saturated fatty acids
      up to 14 carbon atoms and in polyunsaturated fatty acids in mothers of preterm
      newborns compared with those of full-term newborns. CONCLUSIONS: It can be
      concluded that gestational age affects human milk fatty acid composition. This
      food is essential for pre-term newborns as it is the source of energetic
      compounds (saturated fatty acids) as well as plastic compounds, (polyunsaturated
      fatty acids) which are essential for the synthesis of structural lipids and
      neural development.

PMID- 19753439
TI  - [Use of alternative or complementary medicine by the pediatric population of a
      community hospital].
AB  - INTRODUCTION: Consultation to complementary and alternative medicines (CAM) in
      the pediatric population is becoming more frequent. OBJECTIVES: To assess the
      prevalence of the consultations, the communication with their doctors and the
      characteristics of patients and families who consult CAM. METHODS: A transversal
      study was done. All healthy children age 4 to 17 who attended with a responsible
      adult to the emergency unit were included. The sample was taken in a consecutive
      non randomized way. RESULTS: Two hundred and eighty carers of the children were
      invited to participate in the study and 246 completed the survey. All of the
      patients had their basic needs satisfied and a health insurance. The medium age
      of the children was 9.2 and the one of the carers 39.6 years. In 72% of the
      visits the carer was the mother and in 24% the father. Some CAM was known by
      84.5% and 13% had consulted in some opportunity. Homeopathy was the most known
      (76%) and consulted (8.8%). 96.7% of the children that used a CAM continued their
      clinical follow-up with their pediatrician but 42% of the carers did not tell
      this to the pediatrician. The carers of the patients who consulted CAM said that
      more time was given in the visit (42%), the symptoms for which their consulted
      got better (78.5%) and they found an answer to their child's health problem
      (87%). CONCLUSIONS: From surveyed people, 84.5% knew about CAM and 13% of the
      children had consulted at some moment. Homeopathy was the most known (76%) and
      the most consulted (8.8%). Almost all of the children that consulted a CAM
      continued their clinical follow-up with their pediatrician but 42% didn't tell
      them about their consultation.

PMID- 19753440
TI  - [Prevalence and characteristics of the vesicoureteral reflux in infants who
      suffered neonatal urinary tract infection].
AB  - INTRODUCTION: The risk of developing renal scars is higher in the first years of
      life, mostly when the patient has vesicoureteral reflux, for that reason is
      necessary to identify this reflux as early as possible. Our aim was to determine
      the prevalence and characteristic of presentation of vesicoureteral reflux in
      infants who suffered neonatal urinary tract infection. METHOD: Observational,
      prospective study, from 1992 to 2007, of a newborn cohort that suffered the first
      urinary tract infection acquired in the community with upper localization for
      clinical criteria, who had been carried out renal ultrasound and mictional
      urethrocystography. We analyzed the clinical and imaging characteristics of the
      vesicoureteral reflux presentation. RESULTS: In 358 patients the median of follow
      up was 19 months (range 1-104). The prevalence rate of vesicoureteral reflux was
      20.9% (IC 95%: 16.4-26.2), prevailing the primary vesicoureteral reflux, with a
      rate of 18.1% patients. The vesicoureteral reflux was unilateral in 40 patients,
      with higher affectation of the left kidney, and bilateral in 35 cases. The
      degrees III or higher of vesicoureteral reflux (65.0%), overcame the low degree I
      or II in the patients with unilateral vesicoureteral reflux (35.0%). There was
      not significant difference by gender. CONCLUSIONS: The presentation of an urinary
      tract infection in the neonatal period was associated with vesicoureteral reflux
      in 20.9% of the cases, most frequently caused by primary vesicoureteral reflux
      and the dilatant degrees. There was not significant difference by gender.

PMID- 19753441
TI  - [Effects on natremia of the intravenous hypotonic fluid administration in
      hospitalized children with acute lower respiratory tract infection].
AB  - INTRODUCTION: Because of the risk of developing hyponatremia, intravenous
      hydratation prescription in children with lower respiratory tract disease (LRTD)
      is challenging. OBJECTIVE: To evaluate if intravenous hypotonic fluid
      administration in children with LRTD leads to hyponatremia. METHODS: Patients
      aged 1 month to 18 years, hospitalized for LRTD, requiring intravenous fluids
      were included. Blood samples to determine sodium levels were obtained before and
      within the first twenty four hours of fluids administration. A serum sodium
      decrease >or= 4 mEq/L was considered significative. Student t test and
      logarithmic regression was used to analyze results (significance level p<0.05).
      RESULTS: From 1039 patients hospitalized with LRTD (58 received intravenous
      fluids), 35 patients met the inclusion criteria. Median age was 3 months (1-60
      months), 57.1% were males. Patients received 59.3 +/- 24 ml/h of intravenous
      fluids, 39.2 +/- 16 ml/h of electrolyte free water and 2 +/- 1.3 mEq/kg of
      sodium. Serum sodium was 141.2 mEq/l in the initial sample and 139.3 mEq/l in the
      second one. Mean serum sodium decrease was 1.9 +/- 4.8 mEq/l (IC 95%: 0.2-3.5; p<
      0.026). Eleven patients had a sodium decrease >or=4 mEq/l, none showed clinical
      manifestation of hyponatremia. For each mEq/l of increase in initial natremia the
      odds of achieving a decrease in serum sodium >or=4 mEq/l increases in 40%
      (OR=1.39; IC 95%: 1.1-1.8). CONCLUSION: A significant decrease in initial serum
      sodium has been observed in 11 of 35 patients. Higher initial serum sodium values
      increase the odds of a significant decrease.

PMID- 19753442
TI  - [Genetic cholestasis].
AB  - During the last 11 years, advances in molecular genetics have changed our
      approach to children with intrahepatic cholestasis. Progress in identification of
      mutated genes now allows genetic diagnosis for several forms of cholestasis
      previously grouped into PFIC (progressive familial intrahepatic cholestasis).
      Three distinct forms: PFIC1, PFIC2, and PFIC3 are the result of mutations in the
      ATP8B1, ABCB11, and ABCB4 genes. The diagnosis is supported on clinical,
      biochemical and histological features. The therapeutic goals in theses diseases
      are alleviate symptoms and improve quality of life. Inborn errors of bile acid
      synthesis represent a subset of familial intrahepatic cholestasis. Replacement
      therapy with ursodeoxycholic acid and cholic acid avoids progression of the liver
      injury.

PMID- 19753443
TI  - [Severe hemolytic anemia due to hemoglobin Hammersmith].
AB  - Most of the hemoglobin variants are the result of single amino acid replacement
      in one of the globin chains. In many cases, these hemoglobinopathies are
      harmless, while in others they determine alterations in the physical and chemical
      properties, raising clinical manifestations of variable severity. In the unstable
      hemoglobinopathies, the changes reduce solubility, inducing the formation of
      precipitates of denaturated hemoglobin (Heinz bodies), which damage the membrane
      and finally destroy the red blood cells prematurely. Up to now, more than 150
      different unstable hemoglobins have been described; most of them cause chronic
      hemolysis, increased by infections or drugs. We report the clinical presentation
      of an unstable hemoglobin (hemoglobin Hammersmith) in a girl with severe
      hemolytic anemia, splenomegaly and red blood cell requirement.

PMID- 19753444
TI  - [Subungual exostosis in a 14 years old boy].
AB  - Subungual exostosis is a benign bony outgrowth surrounded by a fibrocartilaginous
      capsule that mainly affects hallux terminal phalanx with subungual or periungular
      localization, and that clinically determines variable degree of nail plate or
      periungular soft tissues alterations, respectively, It is uncommon in childhood
      and more frequent in females. Clinical suspicion is confirmed by the radiographic
      finding of a distinct trabecular bone growth arising from the dorsal aspect of
      the phalanx of the affected finger, on the lateral incidence. Curettage or
      surgical excision is the treatment of choice. We report a case of subungual
      exostosis located at the hallux in a 14-year-old boy suffering from subungual
      exostosis of the hallux that presented the characteristic triad of this entity:
      subungular tumor with nail plate deformity, digital pain and radiologic typical
      findings.

PMID- 19753445
TI  - [Iron deficiency anemia. Guideline for diagnosis and treatment].
AB  - Iron deficiency is the most important cause of anemia. Preschooler children are
      particularly vulnerable; a recent analysis reported a prevalence rate higher than
      35% among children below 2 year of age. Its early detection, right treatment, and
      suitable prophylaxis is currently a priority in our country. This guideline
      establishes the definition of anemia in relation to chronological age,
      gestational age, and habitat, reviews principal aspects of iron metabolism,
      enumerates main causes of iron deficiency, and set guidelines for diagnosis,
      detection, differential diagnosis, treatment and prevention of iron deficiency
      anemia.

PMID- 19753447
TI  - [Congenital adrenal hyperplasia salt-wasting form in males during the neonatal
      period. Can we anticipate to metabolic emergency?].
AB  - Congenital adrenal hyperplasia is a group of disorders resulting from the
      deficiency of one of the five enzymes required for the synthesis of cortisol. The
      most frequent is the steroid 21-hydroxylase deficiency, accounting for more than
      90% of the cases. The capacity of aldosterone synthesis is also decreased in 75%
      of the affected infants, resulting in salt-wasting type and life-threatening
      metabolic crisis. Affected males have not overt abnormality of the external
      genitalia and are detected when they develop a salt-losing crisis. The aim is to
      describe the devastating clinical presentation of the salt-wasting in two
      affected boys in the period without screening, and the advantages of the
      screening era in one girl having a simple virilizing form. Careful medical
      history, earlier clinical suspicion and a screening program would have helped us
      anticipate the diagnosis and, therefore, prevent salt-wasting crisis.

PMID- 19753446
TI  - [Consensus on drowning prevention. "The child and the water." 2nd part].

PMID- 19753448
TI  - [Description of the case presented in the previous issue: Meckel's diverticulum].

PMID- 19753452
TI  - Chagas disease centennial anniversary celebration: historical overview and
      prospective proposals aiming to maintain vector control and improve patient
      prognosis--a permanent challenge.

PMID- 19753453
TI  - Paleoparasitology of Chagas disease--a review.
AB  - One hundred years since the discovery of Chagas disease associated with
      Trypanosoma cruzi infection, growing attention has focused on understanding the
      evolution in parasite-human host interaction. This interest has featured studies
      and results from paleoparasitology, not only the description of lesions in
      mummified bodies, but also the recovery of genetic material from the parasite and
      the possibility of analyzing such material over time. The present study reviews
      the evidence of Chagas disease in organic remains excavated from archeological
      sites and discusses two findings in greater detail, both with lesions suggestive
      of chagasic megacolon and confirmed by molecular biology techniques. One of these
      sites is located in the United States, on the border between Texas and Mexico and
      the other in state of Minas Gerais, in the Brazilian cerrado (savannah). Dated
      prior to contact with Europeans, these results confirm that Chagas disease
      affected prehistoric human groups in other regions outside the Andean altiplanos
      and other transmission areas on the Pacific Coast, previously considered the
      origin of T. cruzi infection in the human host.

PMID- 19753454
TI  - Current epidemiological trends for Chagas disease in Latin America and future
      challenges in epidemiology, surveillance and health policy.
AB  - Chagas disease, named after Carlos Chagas, who first described it in 1909, exists
      only on the American Continent. It is caused by a parasite, Trypanosoma cruzi,
      which is transmitted to humans by blood-sucking triatomine bugs and via blood
      transfusion. Chagas disease has two successive phases: acute and chronic. The
      acute phase lasts six-eight weeks. Several years after entering the chronic
      phase, 20-35% of infected individuals, depending on the geographical area, will
      develop irreversible lesions of the autonomous nervous system in the heart,
      oesophagus and colon, and of the peripheral nervous system. Data on the
      prevalence and distribution of Chagas disease improved in quality during the
      1980s as a result of the demographically representative cross-sectional studies
      in countries where accurate information was not previously available. A group of
      experts met in Brasilia in 1979 and devised standard protocols to carry out
      countrywide prevalence studies on human T. cruzi infection and triatomine house
      infestation. Thanks to a coordinated multi-country programme in the Southern Cone
      countries, the transmission of Chagas disease by vectors and via blood
      transfusion was interrupted in Uruguay in 1997, in Chile in 1999 and in Brazil in
      2006; thus, the incidence of new infections by T. cruzi across the South American
      continent has decreased by 70%. Similar multi-country initiatives have been
      launched in the Andean countries and in Central America and rapid progress has
      been reported towards the goal of interrupting the transmission of Chagas
      disease, as requested by a 1998 Resolution of the World Health Assembly. The cost
      benefit analysis of investment in the vector control programme in Brazil
      indicates that there are savings of US$17 in medical care and disabilities for
      each dollar spent on prevention, showing that the programme is a health
      investment with very high return. Many well-known research institutions in Latin
      America were key elements of a worldwide network of laboratories that carried out
      basic and applied research supporting the planning and evaluation of national
      Chagas disease control programmes. The present article reviews the current
      epidemiological trends for Chagas disease in Latin America and the future
      challenges in terms of epidemiology, surveillance and health policy.

PMID- 19753455
TI  - Epidemiology, control and surveillance of Chagas disease: 100 years after its
      discovery.
AB  - Chagas disease originated millions of years ago as an enzootic infection of wild
      animals and began to be transmitted to humans as an anthropozoonosis when man
      invaded wild ecotopes. While evidence of human infection has been found in
      mummies up to 9,000 years old, endemic Chagas disease became established as a
      zoonosis only in the last 200-300 years, as triatomines adapted to domestic
      environments. It is estimated that 15-16 million people are infected with
      Trypanosoma cruzi in Latin America, and 75-90 million are exposed to infection.
      Control of Chagas disease must be undertaken by interrupting its transmission by
      vectors and blood transfusions, improving housing and areas surrounding
      dwellings, providing sanitation education for exposed populations and treating
      acute and recently infected chronic cases. These measures should be complemented
      by surveillance and primary, secondary and tertiary care.

PMID- 19753456
TI  - Elimination of Chagas disease transmission: perspectives.
AB  - One hundred years after its discovery by Carlos Chagas, American trypanosomiasis,
      or Chagas disease, remains an epidemiologic challenge. Neither a vaccine nor an
      ideal specific treatment is available for most chronic cases. Therefore, the
      current strategy for countering Chagas disease consists of preventive actions
      against the vector and transfusion-transmitted disease. Here, the present
      challenges, including congenital and oral transmission of Trypanosoma cruzi
      infections, as well as the future potential for Chagas disease elimination are
      discussed in light of the current epidemiological picture. Finally, a list of
      challenging open questions is presented about Chagas disease control, patient
      management, programme planning and priority definitions faced by researchers and
      politicians.

PMID- 19753457
TI  - Biology, diversity and strategies for the monitoring and control of triatomines-
      Chagas disease vectors.
AB  - Despite the relevant achievements in the control of the main Chagas disease
      vectors Triatoma infestans and Rhodnius prolixus, several factors still promote
      the risk of infection. The disease is a real threat to the poor rural regions of
      several countries in Latin America. The current situation in Brazil requires
      renewed attention due to its high diversity of triatomine species and to the
      rapid and drastic environmental changes that are occurring. Using the biology,
      behaviour and diversity of triatomines as a basis for new strategies for
      monitoring and controlling the vectorial transmission are discussed here. The
      importance of ongoing long-term monitoring activities for house infestations by
      T. infestans, Triatoma brasiliensis, Panstrongylus megistus, Triatoma rubrovaria
      and R. prolixus is also stressed, as well as understanding the invasion by
      sylvatic species. Moreover, the insecticide resistance is analysed. Strong
      efforts to sustain and improve surveillance procedures are crucial, especially
      when the vectorial transmission is considered interrupted in many endemic areas.

PMID- 19753458
TI  - Sustainability of vector control strategies in the Gran Chaco Region: current
      challenges and possible approaches.
AB  - Sustainability has become a focal point of the international agenda. At the heart
      of its range of distribution in the Gran Chaco Region, the elimination of
      Triatoma infestans has failed, even in areas subject to intensive professional
      vector control efforts. Chagas disease control programs traditionally have been
      composed of two divorced entities: a vector control program in charge of routine
      field operations (bug detection and insecticide spraying) and a disease control
      program in charge of screening blood donors, diagnosis, etiologic treatment and
      providing medical care to chronic patients. The challenge of sustainable
      suppression of bug infestation and Trypanosoma cruzi transmission can be met
      through integrated disease management, in which vector control is combined with
      active case detection and treatment to increase impact, cost-effectiveness and
      public acceptance in resource-limited settings. Multi-stakeholder involvement may
      add sustainability and resilience to the surveillance system. Chagas vector
      control and disease management must remain a regional effort within the frame of
      sustainable development rather than being viewed exclusively as a matter of
      health pertinent to the health sector. Sustained and continuous coordination
      between governments, agencies, control programs, academia and the affected
      communities is critical.

PMID- 19753459
TI  - Wild Triatoma infestans, a potential threat that needs to be monitored.
AB  - The current persistence of Triatoma infestans, and therefore of Chagas disease
      transmission, in the Andean valleys of Bolivia and the Gran Chaco (precisely
      where wild populations of the vector are widespread), indicates a possible
      relationship between these two occurrences. This paper provides an overview of
      the current knowledge regarding wild T. infestans in Bolivia. The different
      morphs of the wild vector, their known distributions and some traits of their
      biology and ecology are presented. Particularly interesting is the considerable
      behavioural and chromatic plasticity that is displayed by wild T. infestans.
      According to the biogeographic region, different morphs of the vector occur in
      rupicolous habitats (common form and Mataral morph in Andean wild T. infestans)
      or arboreal ones ('dark morph' populations from the Chaco). The high genetic
      variability found at the microgeographical scale in Andean wild T. infestans
      favours the hypothesis that the Andes were the centre of origin and dispersal of
      T. infestans throughout South America. The relevant question regarding the origin
      of domestic populations is also addressed. Finally, current considerations of the
      epidemiological significance of wild T. infestans are discussed in the context of
      recent discoveries. Even if several observations support the epidemiological risk
      represented by wild T. infestans, the climatic and environmental conditions of
      their distribution areas would not favour the continued flow of triatomines
      between sylvatic refuges and domestic environments.

PMID- 19753460
TI  - Exploiting triatomine behaviour: alternative perspectives for their control.
AB  - Living in close association with a vertebrate host and feeding on its blood
      requires different types of adaptations, including behavioural adjustments.
      Triatomines exhibit particular traits associated with the exploitation of their
      habitat and food sources and these traits have been the subject of intense
      analysis. Many aspects of triatomine behaviour have been relatively well
      characterised and some attempts to exploit the behaviours have been undertaken.
      Baited traps based on host-associated cues, artificial refuges and light-traps
      are some of the tools used. Here we discuss how our knowledge of the biology of
      Chagas disease vectors may help us sample and detect these insects and even
      increase the efficiency of control measures.

PMID- 19753461
TI  - Sylvatic triatominae: a new challenge in vector control transmission.
AB  - Over the last 10 years, Uruguay, Chile and Brazil have been certified as being
      free from disease transmission by Triatoma infestans, the main domiciliated
      vector for Chagas disease in the Southern Cone countries. This demonstrates that
      programmes addressing the vector for the disease's transmission are effective.
      These programmes have resulted in a dramatic decrease in the incidence of Chagas
      disease in Latin America. Guatemala was certified a few months ago as being free
      from disease transmission by Rhodnius prolixus, the main domiciliated vector for
      Chagas disease in Central American countries. However, the main concern for
      different countries' current control programmes is the continuity and
      sustainability of future vector control actions. The prevalence and incidence
      figures for individuals infected by Trypanosoma cruzi in Mexico and Andean and
      Central American countries highlights the need for broadened strategies in the
      struggle against the disease and its vectors. A number of triatomine insects are
      parasite vectors, each with a different life history. Therefore, it is important
      that new vector control strategies be proposed, keeping in mind that some species
      are found in peridomiciliary areas and wild ecotopes. The only viable control
      strategy is to reduce human interactions with vector insects so that the re
      infestation and re-colonisation of human habitats will not take place.

PMID- 19753462
TI  - A century of research: what have we learned about the interaction of Trypanosoma
      cruzi with host cells?
AB  - Since the discovery of Trypanosoma cruzi and the brilliant description of the
      then-referred to 'new tripanosomiasis' by Carlos Chagas 100 years ago, a great
      deal of scientific effort and curiosity has been devoted to understanding how
      this parasite invades and colonises mammalian host cells. This is a key step in
      the survival of the parasite within the vertebrate host, and although much has
      been learned over this century, differences in strains or isolates used by
      different laboratories may have led to conclusions that are not as universal as
      originally interpreted. Molecular genotyping of the CL-Brener clone confirmed a
      genetic heterogeneity in the parasite that had been detected previously by other
      techniques, including zymodeme or schizodeme (kDNA) analysis. T. cruzi can be
      grouped into at least two major phylogenetic lineages: T. cruzi I, mostly
      associated with the sylvatic cycle and T. cruzi II, linked to human disease;
      however, a third lineage, T. cruziIII, has also been proposed. Hybrid isolates,
      such as the CL-Brener clone, which was chosen for sequencing the genome of the
      parasite (Elias et al. 2005, El Sayed et al. 2005a), have also been identified.
      The parasite must be able to invade cells in the mammalian host, and many studies
      have implicated the flagellated trypomastigotes as the main actor in this
      process. Several surface components of parasites and some of the host cell
      receptors with which they interact have been described. Herein, we have attempted
      to identify milestones in the history of understanding T. cruzi- host cell
      interactions. Different infective forms of T. cruzi have displayed unexpected
      requirements for the parasite to attach to the host cell, enter it, and
      translocate between the parasitophorous vacuole to its final cytoplasmic
      destination. It is noteworthy that some of the mechanisms originally proposed to
      be broad in function turned out not to be universal, and multiple interactions
      involving different repertoires of molecules seem to act in concert to give rise
      to a rather complex interplay of signalling cascades involving both parasite and
      cellular components.

PMID- 19753463
TI  - Structural organization of Trypanosoma cruzi.
AB  - Since the initial description of Trypanosoma cruzi by Carlos Chagas in 1909,
      several research groups have used different microscopic techniques to obtain
      detailed information about the various developmental stages found in the life
      cycle of this intracellular parasite. This review describes the present knowledge
      on the organization of the most important structures and organelles found in the
      protozoan, such as the cell surface, flagellum, cytoskeleton, kinetoplast
      mitochondrion complex, glycosome, acidocalcisome, contractile vacuole, lipid
      inclusions, the secretory pathway, endocytic pathway and the nucleus.

PMID- 19753464
TI  - Molecular mechanisms of Trypanosoma cruzi infection by oral route.
AB  - Frequent reports on outbreaks of acute Chagas' disease by ingestion of food
      contaminated with parasites from triatomine insects illustrate the importance of
      this mode of transmission. Studies on oral Trypanosoma cruzi infection in mice
      have indicated that metacyclic trypomastigotes invade the gastric mucosal
      epithelium. A key molecule in this process is gp82, a stage-specific surface
      glycoprotein that binds to both gastric mucin and to target epithelial cells. By
      triggering Ca2+ signalling, gp82 promotes parasite internalisation. Gp82 is
      relatively resistant to peptic digestion at acidic pH, thus preserving the
      properties critical for oral infection. The infection process is also influenced
      by gp90, a metacyclic stage-specific molecule that negatively regulates the
      invasion process. T. cruzi strains expressing high gp90 levels invade cells
      poorly in vitro. However, their infectivity by oral route varies considerably due
      to varying susceptibilities of different gp90 isoforms to peptic digestion.
      Parasites expressing pepsin-susceptible gp90 become highly invasive against
      target cells upon contact with gastric juice. Such is the case of a T. cruzi
      isolate from an acute case of orally acquired Chagas' disease; the gp90 from this
      strain is extensively degraded upon short period of parasite permanence in the
      gastric milieu. If such an exacerbation of infectivity occurs in humans, it may
      be responsible for the severity of Chagas' disease reported in outbreaks of oral
      infection.

PMID- 19753465
TI  - Trypanosoma cruzi: ancestral genomes and population structure.
AB  - Although the genome of Trypanosoma cruzi has been completely sequenced, little is
      known about its population structure and evolution. Since 1999, two major
      evolutionary lineages presenting distinct epidemiological characteristics have
      been recognised: T. cruzi I and T. cruzi II. We describe new and important
      aspects of the population structure of the parasite, and unequivocally
      characterise a third ancestral lineage that we propose to name T. cruzi III.
      Through a careful analysis of haplotypes (blocks of genes that are stably
      transmitted from generation to generation of the parasite), we inferred at least
      two hybridisation events between the parental lineages T. cruzi II and T. cruzi
      III. The strain CL Brener, whose genome was sequenced, is one such hybrid. Based
      on these results, we propose a simple evolutionary model based on three ancestral
      genomes, T. cruzi I, T. cruzi II and T. cruzi III. At least two hybridisation
      events produced evolutionarily viable progeny, and T. cruzi III was the
      cytoplasmic donor for the resulting offspring (as identified by the mitochondrial
      clade of the hybrid strains) in both events. This model should be useful to
      inform evolutionary and pathogenetic hypotheses regarding T. cruzi.

PMID- 19753466
TI  - Diagnosis of Chagas disease: what has been achieved? What remains to be done with
      regard to diagnosis and follow up studies?
AB  - In the acute phase and in the chronic forms of Chagas disease, the etiological
      diagnosis may be performed by detection of the parasite using direct or indirect
      parasitological methods and by the presence of antibodies in the serum by way of
      serological tests. Several techniques are easily available, ranging from the
      simplest wet smear preparation to immuno-enzymatic assays with recombinant
      antigens that will meet most diagnostic needs. Other tests under evaluation
      include a molecular test using polymerase chain reaction, which has shown
      promising results and may be used as a confirmatory test both in the acute and
      chronic phases of the disease. Better rapid tests are needed for diagnosis, some
      of which are already under evaluation. Additionally, there is a need for tools
      that can identify patients cured shortly after specific treatment. Other needs
      include a marker for prognosis and early diagnosis of congenital transmission.

PMID- 19753467
TI  - Usefulness of PCR-based assays to assess drug efficacy in Chagas disease
      chemotherapy: value and limitations.
AB  - One major goal of research on Chagas disease is the development of effective
      chemotherapy to eliminate the infection from individuals who have not yet
      developed cardiac and/or digestive disease manifestations. Cure evaluation is the
      more complex aspect of its treatment, often leading to diverse and controversial
      results. The absence of reliable methods or a diagnostic gold standard to assess
      etiologic treatment efficacy still constitutes a major challenge. In an effort to
      develop more sensitive tools, polymerase chain reaction (PCR)-based assays were
      introduced to detect low amounts of Trypanosoma cruzi DNA in blood samples from
      chagasic patients, thus improving the diagnosis and follow-up evaluation after
      chemotherapy. In this article, I review the main problems concerning drug
      efficacy and criteria used for cure estimation in treated chagasic patients, and
      the work conducted by different groups on developing PCR methodologies to monitor
      treatment outcome of congenital infections as well as recent and late chronic T.
      cruzi infections.

PMID- 19753468
TI  - Viability study of a multiplex diagnostic platform for Chagas disease.
AB  - A new multiplex assay platform was evaluated to detect Trypanosoma cruzi
      infection using the recombinant antigens CRA, FRA, CRAFRA fusion and parasite
      lysate. The antigens presented different sensitivity and specificity in a
      singleplex test when compared to a serial dilution of two pools comprising 10
      positive serum samples and one pool of 10 negative samples. The recombinant
      protein CRA presented lower sensitivity (55%) in contrast to the 100% specificity
      and sensitivity of FRA, CRAFRA and T. cruzi lysate. These antigens also showed
      good results in a duplex test and the duplex test with CRAFRA/T. cruzi lysate
      showed better performance with 100% specificity and sensitivity, as well as a
      lower cut-off value in comparison to the other duplex test, FRA/T. cruzi lysate.
      Hence, when the antigens were used in duplex format, both tests showed decreased
      cut-off values and no interference between different bead sets, resulting in
      increasing sensitivity and specificity. The results of these multiplex tests show
      that they could be an alternative to singleplex detection for Chagas disease, and
      also indicate the necessity of using multiplex diagnostic tools to increase the
      sensitivity and specificity for diagnostic tests. Emerging data from the T. cruzi
      genome and from its ORFeome project will also allow the identification of new
      antigens for this disease detection application.

PMID- 19753469
TI  - The utility of anti-trypomastigote lytic antibodies for determining cure of
      Trypanosoma cruzi infections in treated patients: an overview and perspectives.
AB  - In previous work, we proposed alternative protocols for following patients with
      treated Chagas disease and these are reviewed herein. Evidence was provided to
      support the following: (i) functional anti-trypomastigote antibodies are
      indicative of ongoing chronic Trypanosoma cruzi infections; (ii) specific
      antibodies detected by conventional serology (CS) with epimastigote extracts,
      fixed trypomastigotes or other parasite antigens may circulate years after
      parasite elimination; (iii) functional antibodies are evidenced by complement
      mediated lysis of freshly isolated trypomastigotes, a test which is 100%
      specific, highly sensitive, and the first to revert after T. cruzi elimination
      and (iv) the parasite target for the lytic antibodies is a glycoprotein of high
      molecular weight (gp160) anchored at the parasite surface. The complement
      regulatory protein has been cloned, sequenced and produced as a recombinant
      protein by other groups and is useful for identifying functional anti-T. cruzi
      antibodies in ELISA tests, thus dispensing with the need for live trypomastigotes
      to manage treated patients. If used instead of CS to define cures for Chagas
      patients, ELISA will avoid unnecessary delays in finding anti-T. cruzi drugs.
      Other highly sensitive techniques for parasite DNA detection, such as PCR, need
      to be standardized and included in future protocols for the management of
      patients with drug-treated Chagas disease.

PMID- 19753470
TI  - Chagas heart disease: pathophysiologic mechanisms, prognostic factors and risk
      stratification.
AB  - Chagas heart disease (CHD) results from infection with the protozoan parasite
      Trypanosoma cruzi and is the leading cause of infectious myocarditis worldwide.
      It poses a substantial public health burden due to high morbidity and mortality.
      CHD is also the most serious and frequent manifestation of chronic Chagas disease
      and appears in 20-40% of infected individuals between 10-30 years after the
      original acute infection. In recent decades, numerous clinical and experimental
      investigations have shown that a low-grade but incessant parasitism, along with
      an accompanying immunological response [either parasite-driven (most likely) or
      autoimmune-mediated], plays an important role in producing myocardial damage in
      CHD. At the same time, primary neuronal damage and microvascular dysfunction have
      been described as ancillary pathogenic mechanisms. Conduction system
      disturbances, atrial and ventricular arrhythmias, congestive heart failure,
      systemic and pulmonary thromboembolism and sudden cardiac death are the most
      common clinical manifestations of chronic Chagas cardiomyopathy. Management of
      CHD aims to relieve symptoms, identify markers of unfavourable prognosis and
      treat those individuals at increased risk of disease progression or death. This
      article reviews the pathophysiology of myocardial damage, discusses the value of
      current risk stratification models and proposes an algorithm to guide mortality
      risk assessment and therapeutic decision-making in patients with CHD.

PMID- 19753471
TI  - Morbidity and prognostic factors in chronic chagasic cardiopathy.
AB  - Chagas disease is a pleomorphic clinical entity that has several unique features.
      The aim of this study is to summarise some of the recent contributions from our
      research group to knowledge of the morbidity and prognostic factors in Chagas
      heart disease. A retrospective study suggested that ischaemic stroke associated
      with left ventricular (LV) apical thrombi is the first clinical manifestation of
      Chagas disease observed in a large proportion of patients. LV function and left
      atrial volume (LAV) are independent risk factors for ischaemic cerebrovascular
      events during follow-up of Chagas heart disease patients. Pulmonary congestion in
      Chagas-related dilated cardiomyopathy is common but usually mild. Although early
      right ventricular (RV) involvement has been described, we have shown by Doppler
      echocardiography that RV dysfunction is evident almost exclusively when it is
      associated with left ventricle dilatation and functional impairment. In addition,
      RV dysfunction is a powerful predictor of survival in patients with heart failure
      secondary to Chagas disease. We have also demonstrated that LAV provides
      incremental prognostic information independent of clinical data and conventional
      echocardiographic parameters that predict survival.

PMID- 19753472
TI  - Therapy, diagnosis and prognosis of chronic Chagas disease: insight gained in
      Argentina.
AB  - The purpose of this review is to describe research findings regarding chronic
      Chagas disease in Argentina that have changed the standards of care for patients
      with Trypanosoma cruzi infection. Indirect techniques (serological tests) are
      still the main tools for the primary diagnosis of infection in the chronic phase,
      but polymerase chain reaction has been shown to be promising. The prognosis of
      patients with heart failure or advanced stages of chagasic cardiomyopathy is
      poor, but a timely diagnosis during the initial stages of the disease would allow
      for prescription of appropriate therapies to offer a better quality of life.
      Treatment of T. cruzi infection is beneficial as secondary prevention to
      successfully cure the infection or to delay, reduce or prevent the progression to
      disease and as primary disease prevention by breaking the chain of transmission.
      Current recommendations have placed the bulk of the diagnostic and treatment
      responsibility on the Primary Health Care System. Overall, the current research
      priorities with respect to Chagas disease should be targeted towards (i) the
      production of new drugs that would provide a shorter treatment course with fewer
      side effects; (ii) the development of new tools to confirm cure after a full
      course of treatment during the chronic phase and (iii) biomarkers to identify
      patients with a high risk of developing diseases.

PMID- 19753473
TI  - All-around care for patients with Chagas disease: a challenge for the XXI
      century.
AB  - In 1987, the University of Pernambuco's Oswaldo Cruz Hospital in Recife, Brazil
      opened its Chagas Disease and Heart Failure Outpatient Clinic with the aim of
      providing its patients all-around care through adoption of a biopsychosocial
      model of care. All-around care involves caring for the patient as a whole human
      being in the context of the biological, psychological and social factors present,
      which are an inherent part of the human condition. One prerequisite for the
      proposed model of care is the participation of a multidisciplinary team of
      trained technical staff committed to this framework. Although the main focus of
      the service is on care, teaching and research are also an important part of its
      work. The Pernambuco Association of Chagas Disease Patients is guided by the same
      model of care and has been carrying out educational activities relating to the
      disease, its treatment and support for patients and family members for several
      years. This Association plays an important role in advocating to public
      authorities on behalf of patients. The accumulated experience of the past 22
      years has shown us that a broad vision of health care can help clinicians and
      policy makers to make decisions that are more in tune with the everyday reality
      of the patient, which in turn has a positive impact on adherence to treatment and
      quality of life.

PMID- 19753474
TI  - Back to the future in Chagas disease: from animal models to patient cohort
      studies, progress in immunopathogenesis research.
AB  - Despite the wealth of information generated by trans-disciplinary research in
      Chagas disease, knowledge about its multifaceted pathogenesis is still
      fragmented. Here we review the body of experimental studies in animal models
      supporting the concept that persistent infection by Trypanosoma cruzi is crucial
      for the development of chronic myocarditis. Complementing this review, we will
      make an effort to reconcile seemingly contradictory results concerning the immune
      profiles of chronic patients from Argentina and Brazil. Finally, we will review
      the results of molecular studies suggesting that parasite-induced inflammation
      and tissue damage is, at least in part, mediated by the activities of trans
      sialidase, mucin-linked lipid anchors (TLR2 ligand) and cruzipain (a kinin
      releasing cysteine protease). One hundred years after the discovery of Chagas
      disease, it is reassuring that basic and clinical research tends to converge,
      raising new perspectives for the treatment of chronic Chagas disease.

PMID- 19753475
TI  - Do Archaea and bacteria co-infection have a role in the pathogenesis of chronic
      chagasic cardiopathy?
AB  - Chronic cardiopathy (CC) in Chagas disease is a fibrotic myocarditis with C5b-9
      complement deposition. Mycoplasma and Chlamydia may interfere with the complement
      response. Proteolytic enzymes and archaeal genes that have been described in
      Trypanosoma cruzi may increase its virulence. Here we tested the hypothesis that
      different ratios of Mycoplasma, Chlamydia and archaeal organisms, which are
      frequent symbionts, may be associated with chagasic clinical forms. MATERIALS AND
      METHODS: eight indeterminate form (IF) and 20 CC chagasic endomyocardial biopsies
      were submitted to in situ hybridization, electron and immunoelectron microscopy
      and PCR techniques for detection of Mycoplasma pneumoniae (MP), Chlamydia
      pneumoniae(CP), C5b-9 and archaeal-like bodies. RESULTS: MP and CP-DNA were
      always present at lower levels in CC than in IF (p < 0.001) and were correlated
      with each other only in CC. Electron microscopy revealed Mycoplasma, Chlamydia
      and two types of archaeal-like bodies. One had electron dense lipid content (EDL)
      and was mainly present in IF. The other had electron lucent content (ELC) and was
      mainly present in CC. In this group, ELC correlated negatively with the other
      microbes and EDL and positively with C5b-9. The CC group was positive for Archaea
      and T. cruzi DNA. In conclusion, different amounts of Mycoplasma, Chlamydia and
      archaeal organisms may be implicated in complement activation and may have a role
      in Chagas disease outcome.

PMID- 19753476
TI  - Cellular and genetic mechanisms involved in the generation of protective and
      pathogenic immune responses in human Chagas disease.
AB  - Perhaps one of the most intriguing aspects of human Chagas disease is the complex
      network of events that underlie the generation of protective versus pathogenic
      immune responses during the chronic phase of the disease. While most individuals
      do not develop patent disease, a large percentage may develop severe forms that
      eventually lead to death. Although many efforts have been devoted to deciphering
      these mechanisms, there is still much to be learned before we can fully
      understand the pathogenesis of Chagas disease. It is clear that the host's immune
      response is decisive in this process. While characteristics of the parasite
      influence the immune response, it is becoming evident that the host genetic
      background plays a fundamental role in the establishment of pathogenic versus
      protective responses. The involvement of three complex organisms, host, parasite
      and vector, is certainly one of the key aspects that calls for multidisciplinary
      approaches towards the understanding of Chagas disease. We believe that now, one
      hundred years after the discovery of Chagas disease, it is imperative to continue
      with highly interactive research in order to elucidate the immune response
      associated with disease evolution, which will be essential in designing
      prophylactic or therapeutic interventions.

PMID- 19753477
TI  - Chagas disease, adipose tissue and the metabolic syndrome.
AB  - Trypanosoma cruzi infection of the adipose tissue of mice triggers the local
      expression of inflammatory mediators and a reduction in the expression of the
      adipokine adiponectin. T. cruzi can be detected in adipose tissue by PCR 300 days
      post-infection. Infection of cultured adipocytes results in increased expression
      of cytokines and chemokines and a reduction in the expression of adiponectin and
      the peroxisome proliferator-activated receptor gamma, both of which are negative
      regulators of inflammation. Infection also results in the upregulation of cyclin
      D1, the Notch pathway, and extracellular signal-regulated kinase and a reduction
      in the expression of caveolin-1. Thus, T. cruzi infection of cultured adipocytes
      leads to an upregulation of the inflammatory process. Since adiponectin null mice
      have a cardiomyopathic phenotype, it is possible that the reduction in
      adiponectin contributes to the pathogenesis of chagasic cardiomyopathy. Adipose
      tissue may serve as a reservoir for T. cruzi from which parasites can become
      reactivated during periods of immunosuppression. T. cruzi infection of mice often
      results in hypoglycemia. In contrast, hyperglycemia as observed in diabetes
      results in increased parasitemia and mortality. Adipose tissue is an important
      target tissue of T. cruzi and the infection of this tissue is associated with a
      profound impact on systemic metabolism, increasing the risk of metabolic
      syndrome.

PMID- 19753478
TI  - Chronic Trypanosoma cruzi-elicited cardiomyopathy: from the discovery to the
      proposal of rational therapeutic interventions targeting cell adhesion molecules
      and chemokine receptors--how to make a dream come true.
AB  - One hundred years ago, Carlos Chagas discovered a new disease, the American
      trypanosomiasis. Chagas and co-workers later characterised the disease's common
      manifestation, chronic cardiomyopathy, and suggested that parasitic persistence
      coupled with inflammation was the key underlying pathogenic mechanism. Better
      comprehension of the molecular mechanisms leading to clinical heart afflictions
      is a prerequisite to developing new therapies that ameliorate inflammation and
      improve heart function without hampering parasite control. Here, we review recent
      data showing that distinct cell adhesion molecules, chemokines and chemokine
      receptors participate in anti-parasite immunity and/or detrimental leukocyte
      trafficking to the heart. Moreover, we offer evidence that CC-chemokine receptors
      may be attractive therapeutic targets aiming to regain homeostatic balance in
      parasite/host interaction thereby improving prognosis, supporting that it is
      becoming a non-phantasious proposal.

PMID- 19753479
TI  - The effects of nitric oxide on the immune system during Trypanosoma cruzi
      infection.
AB  - Trypanosoma cruzi infection triggers substantial production of nitric oxide (NO),
      which has been shown to have protective and toxic effects on the host's immune
      system. Sensing of trypomastigotes by phagocytes activates the inducible NO
      synthase (NOS2) pathway, which produces NO and is largely responsible for
      macrophage-mediated killing of T. cruzi. NO is also responsible for modulating
      virtually all steps of innate and adaptive immunity. However, NO can also cause
      oxidative stress, which is especially damaging to the host due to increased
      tissue damage. The cytokines IFN-gamma and TNF-alpha, as well as chemokines, are
      strong inducers of NOS2 and are produced in large amounts during T. cruzi acute
      infection. Conversely, TGF-beta and IL-10 negatively regulate NO production. Here
      we discuss the recent evidence describing the mechanisms by which NO is able to
      exert its antimicrobial and immune regulatory effects, the mechanisms involved in
      the oxidative stress response during infection and the implications of NO for the
      development of therapeutic strategies against T. cruzi.

PMID- 19753480
TI  - Innate immunity and regulatory T-cells in human Chagas disease: what must be
      understood?
AB  - There is a general consensus that during chronic Trypanosoma cruzi infection, the
      host immune system induces complex processes to ensure the control of parasite
      growth while preserving the potential to mount and maintain a life-long
      controlled humoral and cellular immune response against the invading pathogen.
      This review summarises evidence in an attempt to elucidate 'what must be
      understood' to further clarify the role of innate immunity in the
      development/maintenance of clinical Chagas disease and the impact of etiological
      treatment on host immunity, highlighting the contributions of the innate immunity
      and regulatory T (Treg) cells. Recently, increasing focus on innate immunity
      suggest that chronic T. cruzi infection may cause morbidity when innate effector
      functions, or the down-regulation of adaptive regulatory mechanisms are lacking.
      In this context, stable asymptomatic host-parasite interactions seem to be
      influenced by the effector/regulatory balance with the participation of
      macrophages, natural killer (NK) and CD8+ T cells in parallel with the
      establishment of regulatory mechanisms mediated by NKT and Treg cells. Moreover,
      a balanced innate immune activation state, apart from Treg cells, may play a role
      in controlling the adverse events triggered by the massive antigen release
      induced by trypanosomicidal agents during Chagas disease etiological treatment.

PMID- 19753481
TI  - Immunological and non-immunological effects of cytokines and chemokines in the
      pathogenesis of chronic Chagas disease cardiomyopathy.
AB  - The pathogenesis of Chagas disease cardiomyopathy (CCC) is not well understood.
      Since studies show that myocarditis is more frequent during the advanced stages
      of the disease, and the prognosis of CCC is worse than that of other dilated
      cardiomyopathies of non-inflammatory aetiology, which suggest that the
      inflammatory infiltrate plays a major role in myocardial damage. In the last
      decade, increasing evidence has shown that inflammatory cytokines and chemokines
      play a role in the generation of the inflammatory infiltrate and tissue damage.
      CCC patients have an increased peripheral production of the inflammatory Th1
      cytokines IFN-gamma and TNF-alpha when compared to patients with the
      asymptomatic/indeterminate form. Moreover, Th1-T cells are the main producers of
      IFN-gamma and TNF-alpha and are frequently found in CCC myocardial inflammatory
      infiltrate. Over the past several years, our group has collected evidence that
      shows several cytokines and chemokines produced in the CCC myocardium may also
      have a non-immunological pathogenic effect via modulation of gene and protein
      expression in cardiomyocytes and other myocardial cell types. Furthermore,
      genetic polymorphisms of cytokine, chemokine and innate immune response genes
      have been associated with disease progression. We will review the molecular and
      immunological mechanisms of myocardial damage in human CCC in light of recent
      findings.

PMID- 19753482
TI  - The importance of apoptosis for immune regulation in Chagas disease.
AB  - Host cell apoptosis plays an important immune regulatory role in parasitic
      infections. Infection of mice with Trypanosoma cruzi, the causative agent of
      Chagas disease, induces lymphocyte apoptosis. In addition, phagocytosis of
      apoptotic cells stimulates the growth of T. cruzi inside host macrophages. In
      spite of progress made in this area, the importance of apoptosis in the
      pathogenesis of Chagas disease remains unclear. Here we review the evidence of
      apoptosis in mice and humans infected with T. cruzi. We also discuss the
      mechanisms by which apoptosis can influence underlying host responses and tissue
      damage during Chagas disease progression.

PMID- 19753484
TI  - Alpha-N-acetylglucosamine-linked O-glycans of sialoglycoproteins (Tc-mucins) from
      Trypanosoma cruzi Colombiana strain.
AB  - Trypanosoma cruzi sialoglycoproteins (Tc-mucins) are mucin-like molecules linked
      to a parasite membrane via a glycosylphosphatidylinositol anchor. We previously
      determined the structures of Tc-mucin O-glycan domains from several T. cruzi
      strains and observed significant differences among them. We now report the amino
      acid content and structure of Tc-mucin O-glycan chains from T. cruzi Colombiana,
      a strain resistant to common trypanocidal drugs. Amino acid analysis demonstrated
      the predominance of threonine residues (42%) and helped to identify the O-glycans
      as belonging to a Tc-mucin family that contain a beta-galactofuranose (beta-Galf)
      residue attached to an alpha-N-acetylglucosamine (alpha-GlcNAc) O-4, with the
      most complex glycan, a pentasaccharide-GlcNAc-ol with a branched
      trigalactopyranose chain, on the GlcNAc O-6. The presence of beta-Galf on O
      glycans from T. cruzi Colombiana mucins supports the use of glycosylation as a
      phylogenetic marker for the classification of Colombiana in the T. cruzi I group.

PMID- 19753483
TI  - Two approaches to discovering and developing new drugs for Chagas disease.
AB  - This review will focus on two general approaches carried out at the Sandler
      Center, University of California, San Francisco, to address the challenge of
      developing new drugs for the treatment of Chagas disease. The first approach is
      target-based drug discovery, and two specific targets, cytochrome P450 CYP51 and
      cruzain (aka cruzipain), are discussed. A 'proof of concept' molecule, the vinyl
      sulfone inhibitor K777, is now a clinical candidate. The preclinical assessment
      compliance for filing as an Investigational New Drug with the United States Food
      and Drug Administration (FDA) is presented, and an outline of potential clinical
      trials is given. The second approach to identifying new drug leads is parasite
      phenotypic screens in culture. The development of an assay allowing high
      throughput screening of Trypanosoma cruzi amastigotes in skeletal muscle cells is
      presented. This screen has the advantage of not requiring specific strains of
      parasites, so it could be used with field isolates, drug resistant strains or
      laboratory strains. It is optimized for robotic liquid handling and has been
      validated through a screen of a library of FDA-approved drugs identifying 65
      hits.

PMID- 19753485
TI  - Perspectives of vaccination in Chagas disease revisited.
AB  - The perspectives for a Chagas Disease vaccine 30 years ago and today are
      compared. Antigens and adjuvants have improved, but logistic problems remain the
      same. Sterilizing vaccines have not been produced and animal models for chronic
      Chagas have not been developed. Vector control has been successful and Chagas
      incidence has come to a halt. We do not have a population candidate to
      vaccination now in Brazil. And if we had, we would not know how to evaluate the
      success of vaccination in a short time period. A vaccine may not seem important
      at the moment. However, scientific reasons and incertitudes about the future
      recommend that a search for a vaccine be continued.

PMID- 19753486
TI  - Swimming against the current: genetic vaccination against Trypanosoma cruzi
      infection in mice.
AB  - Vaccines have had an unquestionable impact on public health during the last
      century. The most likely reason for the success of vaccines is the robust
      protective properties of specific antibodies. However, antibodies exert a strong
      selective pressure and many microorganisms, such as the obligatory intracellular
      parasite Trypanosoma cruzi, have been selected to survive in their presence.
      Although the host develops a strong immune response to T. cruzi, they do not
      clear the infection and instead progress to the chronic phase of the disease.
      Parasite persistence during the chronic phase of infection is now considered the
      main factor contributing to the chronic symptoms of the disease. Based on this
      finding, containment of parasite growth and survival may be one method to avoid
      the immunopathology of the chronic phase. In this context, vaccinologists have
      looked over the past 20 years for other immune effector mechanisms that could
      eliminate these antibody-resistant pathogens. We and others have tested the
      hypothesis that non-antibody-mediated cellular immune responses (CD4+ Th1 and
      CD8+ Tc1 cells) to specific parasite antigens/genes expressed by T. cruzi could
      indeed be used for the purpose of vaccination. This hypothesis was confirmed in
      different mouse models, indicating a possible path for vaccine development.

PMID- 19753487
TI  - Protective immunity against Trypanosoma cruzi.
AB  - Upon infection, Trypanosoma cruzi triggers a strong immune response that has both
      protective and pathological consequences. In this work, several important
      questions regarding protective immunity are reviewed. Emphasis is placed on
      recent studies of the important protective role of CD8+ T cells and on previous
      studies of immunisation of domestic T. cruzi reservoirs that sought to address
      practical vaccination problems. Research on the maturation of memory cells and
      studies indicating that the prevalence of T. cruzi-specific T-cell responses and
      a high frequency of committed CD8+ T cells are associated with better clinical
      outcomes are also reviewed. Additionally, animal models in which protection was
      achieved without immunopathological consequences are discussed.

PMID- 19753488
TI  - Proline racemases: insights into Trypanosoma cruzi peptides containing D-proline.
AB  - Trypanosoma cruzi proline racemases (TcPRAC) are homodimeric enzymes that
      interconvert the L and D-enantiomers of proline. At least two paralogous copies
      of proline racemase (PR) genes are present per parasite haploid genome and they
      are differentially expressed during T. cruzi development. Non-infective
      epimastigote forms that overexpress PR genes differentiate more readily into
      metacyclic infective forms that are more invasive to host cells, indicating that
      PR participates in mechanisms of virulence acquisition. Using a combination of
      biochemical and enzymatic methods, we show here that, in addition to free D-amino
      acids, non-infective epimastigote and infective metacyclic parasite extracts
      possess peptides composed notably of D-proline. The relative contribution of
      TcPRAC to D-proline availability and its further assembly into peptides was
      estimated through the use of wild-type parasites and parasites over-expressing
      TcPRAC genes. Our data suggest that D-proline-bearing peptides, similarly to the
      mucopeptide layer of bacterial cell walls, may be of benefit to T. cruzi by
      providing resistance against host proteolytic mechanisms.

PMID- 19753489
TI  - Experimental chemotherapy for Chagas disease: 15 years of research contributions
      from in vivo and in vitro studies.
AB  - Chagas disease, which is caused by the intracellular parasite Trypanosoma cruzi,
      is a neglected illness with 12-14 million reported cases in endemic geographic
      regions of Latin America. While the disease still represents an important public
      health problem in these affected areas, the available therapy, which was
      introduced more than four decades ago, is far from ideal due to its substantial
      toxicity, its limited effects on different parasite stocks, and its poor activity
      during the chronic phase of the disease. For the past 15 years, our group, in
      collaboration with research groups focused on medicinal chemistry, has been
      working on experimental chemotherapies for Chagas disease, investigating the
      biological activity, toxicity, selectivity and cellular targets of different
      classes of compounds on T. cruzi. In this report, we present an overview of these
      in vitro and in vivo studies, focusing on the most promising classes of compounds
      with the aim of contributing to the current knowledge of the treatment of Chagas
      disease and aiding in the development of a new arsenal of candidates with anti-T.
      cruzi efficacy.

PMID- 19753490
TI  - Ergosterol biosynthesis and drug development for Chagas disease.
AB  - This article presents an overview of the currently available drugs nifurtimox
      (NFX) and benznidazole (BZN) used against Trypanosoma cruzi, the aetiological
      agent of Chagas disease; herein we discuss their limitations along with potential
      alternatives with a focus on ergosterol biosynthesis inhibitors (EBI). These
      compounds are currently the most advanced candidates for new anti-T. cruzi agents
      given that they block de novo production of 24-alkyl-sterols, which are essential
      for parasite survival and cannot be replaced by a host's own cholesterol. Among
      these compounds, new triazole derivatives that inhibit the parasite's C14alpha
      sterol demethylase are the most promising, as they have been shown to have
      curative activity in murine models of acute and chronic Chagas disease and are
      active against NFX and BZN-resistant T. cruzi strains; among this class of
      compounds, posaconazole (Schering-Plough Research Institute) and ravuconazole
      (Eisai Company) are poised for clinical trials in Chagas disease patients in the
      short term. Other T. cruzi-specific EBI, with in vitro and in vivo potency,
      include squalene synthase, lanosterol synthase and squalene epoxidase-inhibitors
      as well as compounds with dual mechanisms of action (ergosterol biosynthesis
      inhibition and free radical generation), but they are less advanced in their
      development process. The main putative advantages of EBI over currently available
      therapies include their higher potency and selectivity in both acute and chronic
      infections, activity against NFX and BZN-resistant T. cruzi strains, and much
      better tolerability and safety profiles. Limitations may include complexity and
      cost of manufacture of the new compounds. As for any new drug, such compounds
      will require extensive clinical testing before being introduced for clinical use,
      and the complexity of such studies, particularly in chronic patients, will be
      compounded by the current limitations in the verification of true parasitological
      cures for T. cruzi infections.

PMID- 19753491
TI  - The BENEFIT trial: testing the hypothesis that trypanocidal therapy is beneficial
      for patients with chronic Chagas heart disease.
AB  - Among the pathophysiological derangements operating in the chronic phase of
      Chagas disease, parasite persistence is likely to constitute the main mechanism
      of myocardial injury in patients with chronic chagasic cardiomyopathy. The
      presence of Trypanosoma cruzi in the heart causes a low-grade, but relentless,
      inflammatory process and induces myocardial autoimmune injury. These facts
      suggest that trypanocidal therapy may positively impact the clinical course of
      patients with chronic Chagas heart disease. However, the experimental and
      clinical evidence currently available is insufficient to support the routine use
      of etiologic treatment in these patients. The BENEFIT project--Benznidazole
      Evaluation for Interrupting Trypanosomiasis--is an international, multicenter,
      double-blind, placebo-controlled trial of trypanocidal treatment with
      benznidazole in patients with chronic Chagas heart disease. This project is
      actually comprised of two studies. The pilot study investigates whether etiologic
      treatment significantly reduces parasite burden, as assessed by polymerase chain
      reaction-based techniques and also determines the safety and tolerability profile
      of the trypanocidal drug in this type of chagasic population. The full-scale
      study determines whether antitrypanosomal therapy with benznidazole reduces
      mortality and other major cardiovascular clinical outcomes in patients with
      chronic Chagas heart disease.

PMID- 19753492
TI  - Current status and perspectives of cell therapy in Chagas disease.
AB  - One century after its discovery, Chagas disease, caused by the protozoan,
      Trypanosoma cruzi, remains a major health problem in Latin America. Mortality and
      morbidity are mainly due to chronic processes that lead to dysfunction of the
      cardiac and digestive systems. About one third of the chronic chagasic
      individuals have or will develop the symptomatic forms of the disease, with
      cardiomyopathy being the most common chronic form. This is a progressively
      debilitating disease for which there are no currently available effective
      treatments other than heart transplantation. Like in other cardiac diseases,
      tissue engineering and cell therapy have been investigated in the past few years
      as a means of recovering the heart function lost as a consequence of chronic
      damage caused by the immune-mediated pathogenic mechanisms elicited in
      individuals with chronic chagasic cardiomyopathy. Here we review the studies of
      cell therapy in animal models and patients with chronic Chagas disease and the
      perspectives of the recovery of the heart function lost due to infection with T.
      cruzi.

PMID- 19753493
TI  - Varieties of confabulation and delusion.
AB  - INTRODUCTION: Different types of confabulation or false memory can arise from
      brain disease. There are competing explanatory theories for the mechanisms
      underlying confabulation. Recent literature has attempted to relate the notion of
      delusion to that of confabulation. METHOD: A brief review of the literature
      relating to these ideas. RESULTS: The varieties of confabulation or false memory
      that can arise from brain disease are considered. The varieties of delusion and
      the contexts in which they arise are considered. Comparisons are made between the
      characteristics of spontaneous confabulation and those of delusional memory.
      CONCLUSION: It is suggested that global theories purporting to account for both
      confabulation and delusions, in whatever circumstances they arise, can have only
      limited explanatory power. On the other hand, there are resemblances between
      confabulation and delusional memory, and the similarities and differences between
      these phenomena deserve further empirical investigation.

PMID- 19753495
TI  - Mycotoxic nephropathy in Bulgarian pigs and chickens: complex aetiology and
      similarity to Balkan endemic nephropathy.
AB  - Spontaneous nephropathy in Bulgaria, which is observed frequently during meat
      inspection and which differs morphologically from the classical description of
      mycotoxic porcine/chicken nephropathy as made in Denmark, was found to have a
      multi-mycotoxic aetiology being mainly provoked by a combined effect of
      ochratoxin A, penicillic acid and fumonisin B1 in addition to a not-yet-known
      metabolite. Mean contamination levels of ochratoxin A were consecutively low
      (188.8 and 376.4 microg kg(-1)) in contrast to high contamination levels of
      fumonisin B1 (5564.1 and 3254.5 microg kg(-1)) and penicillic acid (838.6 and
      904.9 microg kg(-1)) for 2006 and 2007, respectively. Some other mycotoxins with
      lower importance such as citrinin, penitrem A, etc., may also influence
      clinicopathological picture of this nephropathy. A heavy contamination with
      Gibberella fujikuroi var. moniliformis (Fusarium verticillioides) and Penicillium
      aurantiogriseum complex (mainly Penicillium polonicum) was observed in almost all
      examined feed samples coming from pig and chick farms with nephropathy problems
      from Bulgaria. In contrast, low contamination with Aspergillus ochraceus,
      Penicillium verrucosum and Penicillium citrinum was observed in the same feed
      samples and these species were isolated as very rare components of the mycobiota.

PMID- 19753496
TI  - Assessing direct analysis in real-time-mass spectrometry (DART-MS) for the rapid
      identification of additives in food packaging.
AB  - The ambient ionization technique direct analysis in real time (DART) was
      characterized and evaluated for the screening of food packaging for the presence
      of packaging additives using a benchtop mass spectrometer (MS). Approximate
      optimum conditions were determined for 13 common food-packaging additives,
      including plasticizers, anti-oxidants, colorants, grease-proofers, and
      ultraviolet light stabilizers. Method sensitivity and linearity were evaluated
      using solutions and characterized polymer samples. Additionally, the response of
      a model additive (di-ethyl-hexyl-phthalate) was examined across a range of sample
      positions, DART, and MS conditions (temperature, voltage and helium flow). Under
      optimal conditions, molecular ion (M+H+) was the major ion for most additives.
      Additive responses were highly sensitive to sample and DART source orientation,
      as well as to DART flow rates, temperatures, and MS inlet voltages, respectively.
      DART-MS response was neither consistently linear nor quantitative in this
      setting, and sensitivity varied by additive. All additives studied were rapidly
      identified in multiple food-packaging materials by DART-MS/MS, suggesting this
      technique can be used to screen food packaging rapidly. However, method
      sensitivity and quantitation requires further study and improvement.

PMID- 19753497
TI  - Migration of novel offset printing inks from cardboard packaging into food.
AB  - We report the migration potential of newly patented low-migration offset printing
      inks from cardboard food packaging and estimate the potential risk of their
      migration into food. The complete printing formulation was available and, due to
      the fact that the solvent compounds in these inks differ from those used in
      conventional printing inks, the investigation focused on these solvents. Instead
      of containing mineral and vegetable oils, the low-migration printing inks are
      based on a novel fatty acid ester. The migration of this alternative solvent was
      investigated according to DIN EN 14338 in Tenax simulant and in different types
      of food. For specific detection of the fatty acid ester, LC-MS/MS (APCI) was
      chosen due to its higher sensitivity and selectivity than GC/MS. Printed
      packaging materials from three different commercially available food products
      (meat, chocolate and sweets) were tested. Migration of the fatty acid ester from
      the packaging into simulants was analysed. For food samples, a clean-up method
      based on solid-phase extraction was developed and migration of the fatty acid
      ester into meat, chocolate and sweets was also demonstrated. Levels of
      contamination of these foods were between 5 and 80 microg fatty acid ester/kg,
      but levels in food were lower than those in simulants.

PMID- 19753498
TI  - Benzene exposure in industries using or manufacturing paint in China--a
      literature review, 1956-2005.
AB  - A systematic review of the Chinese literature was conducted from 1956 to 2005.
      The survey included both online and manual searching, as well as expert
      discussions aimed at providing insight into factors affecting benzene exposure
      levels in paint/coatings industries. Data extracted from 204 papers included: (1)
      year of occurrence, (2) type of paint/coatings products, (3) type of industries
      where the products were used or produced, (4) job titles and work activities, (5)
      type of literature searched, (6) working conditions whenever data were available,
      and (7) exposure levels. Most benzene measurements were short-term samples for
      comparison with the Chinese maximum allowable concentration standard. The
      accuracy and precision of the sampling and analytical methods were not reported.
      The distribution of benzene concentrations was tested and found to fit neither
      normal nor lognormal distributions. Analysis of variance (comparison for more
      than two groups) and t-test (comparison for two groups) were conducted on Blom
      transformed benzene concentration data. The overall median benzene exposure
      levels were 215, 82, 31, and 6 mg/m(3) during the periods 1956-1978, 1979-1989,
      1990-2001, and 2002-2005, respectively. Mean benzene exposure was significantly
      lower for paint manufacturing than paint spraying. No significant difference was
      found among paint types and benzene exposure for paint application. Benzene
      exposure was significantly higher in workplaces judged to have poor ventilation.
      No significant differences were found in benzene exposure as a function of
      industry type. Even though substantially lower when compared with levels in the
      past, recent benzene exposure measurements suggested that many facilities in the
      paint/coatings industries in China still have benzene concentrations that are
      above the current China occupational exposure limit for benzene (6 mg/m(3) as a
      time-weighted average). Benzene concentrations from the present exercise, while
      not directly supporting quantitative retrospective exposure estimating, provide
      insight on relative benzene exposure for painting tasks in the reported
      industries over time.

PMID- 19753499
TI  - HIV transmission risk at a gay bathhouse.
AB  - Previous research found up to 14% of men who go to bathhouses engage in
      unprotected anal intercourse (UAI) and tend to have multiple sexual partners
      during their bathhouse visit, thus appearing to support concerns that such venues
      could foster acute outbreaks of new HIV infections. We conducted a two-stage
      probability sample of men exiting a gay bathhouse, and focused our analysis on
      whether the partnering patterns of the men who engaged in UAI present such a
      risk. Among patrons who had oral or anal sex during their visit (n = 758), 16.7%
      were HIV+, and 13.9% engaged in UAI. Although men had multiple sex partners
      during a visit, they had UAI with only one of those partners, on average, and
      withdrawal prior to ejaculation occurred in the vast majority of UAI incidences.
      Thus, the risk of sexual transmission of HIV during the bathhouse visit was
      typically within isolated dyads rather than patterns of multiple sexual
      encounters that might put many men at risk during a single visit, and men who did
      engage in UAI tended to withdraw prior to ejaculation, potentially mitigating the
      risk of HIV transmission.

PMID- 19753500
TI  - Effect of Asteracantha longifolia seeds on the sexual behaviour of male rats.
AB  - The aim of the present study was to study the effect of seeds of Asteracantha
      longifolia on the sexual behaviour of male albino rats. The ethanolic extract of
      seeds of A. longifolia was administered to groups of rats in 100, 150 and 200 mg
      kg-1 doses for a period of 28 days, and the action compared with control rats.
      The changes in body and organ weight, sexual behaviour, histo-architecture and
      fructose levels of seminal vesicles were observed. The sexual behaviour was
      assessed by determining parameters such as mount frequency (MF), intromission
      latency, mount latency (ML) and post-ejaculatory latency. The ethanolic extract
      exhibited pronounced anabolic effects in treated animals, as evidenced by gains
      in the body and reproductive organ weights. Increased spermatogenesis due to
      treatment with extracts was also witnessed in transverse section. The treatment
      further markedly affected sexual behaviour of the animals, as reflected by the
      reduction of ML, increase in MF and enhanced attractability towards females. A
      significant increase in the sperm count as well as fructose levels of seminal
      vesicles was noted.

PMID- 19753501
TI  - Role of Mangifera indica bark polyphenols on rat gastric mucosa against ethanol
      and cold-restraint stress.
AB  - This study was carried out in order to investigate the potential and antioxidant
      effects of polyphenols from Mangifera indica stem bark against gastric damage
      induced by ethanol and cold-restraint stress. The polyphenols possess good
      capacity for scavenging nitric oxide (NO) radical and ferric-reducing antioxidant
      power (FRAP) assay in vitro. Rats were sacrificed after the experiment, and their
      stomachs were removed for biochemical and histopathological analysis. The
      severity of lesions was found to markedly decrease by the administration of
      polyphenols in both models. The increased gastric nitrite level of ethanol
      administered rats were significantly (p < 0.001) reduced by polyphenol treatment.
      Administration of polyphenols reduced thiobarbituric acid reactive substance
      (TBARS) level and increased the GSH level significantly in a dose-dependent
      manner in both models. Our study revealed the ulcer-protective effects of the
      polyphenols and could possibly reside for the most part on its anti-radical
      effects.

PMID- 19753502
TI  - A new cytotoxic iridoid from Callicarpa nudiflora.
AB  - A new iridoid, named nudifloside (1), together with three known compounds, was
      isolated from the EtOH extract of the aerial parts of Callicarpa nudiflora Hook.
      The structures were elucidated by a study of their physical and spectral data.
      Nudifloside (1) and the isolated known compound linearoside (2) displayed
      inhibitory effects towards chronic myelogenous leukaemia K562 cell line, with
      IC(50) values of 20.7 and 36.0 microg mL(-1), respectively.

PMID- 19753503
TI  - The twilight zone between health and sickness: a qualitative exploration with
      asymptomatic BRCA1 and 2 mutation carriers.
AB  - PURPOSE: To explore the way in which asymptomatic women diagnosed with mutation
      in BRCA1 or BRCA2 genes give meaning to their family scripts and to the dialectic
      between being concurrently healthy and at high risk for breast and ovarian
      cancer, vis-a-vis their way of coping with risks. METHODS: Seventeen asymptomatic
      Israeli women diagnosed as BRCA1 or 2 mutation carriers participated in the
      study. In-depth semi-structured interviews were conducted. Data were analyzed
      using qualitative-phenomenological methods. RESULTS: The following themes were
      revealed: (1) Cancer or surgery: the dominant fear; (2) Family clock; (3)
      Knowledge is power, and (4) Mother's story shapes daughter's construction of
      experience. CONCLUSION: Breast and ovarian cancer worry was a major factor in
      opting for prophylactic oophorectomy. Family scripts, the hope to be healthy and
      the wish to live through significant stages in family life may lead to the choice
      of prophylactic oophorectomy among asymptomatic BRCA1 or 2 mutation carriers.
      However, it does not propel these women to opt for bilateral prophylactic
      mastectomy. Listening to different voices regarding risk reduction modalities is
      crucial among genetic counselors and health providers for health promotion in
      women at high risk.

PMID- 19753504
TI  - Physicians' and women's views on hormone therapy and breast cancer risk after the
      WHI: a qualitative study.
AB  - BACKGROUND: The use of menopausal hormone therapy (HT) has significantly declined
      since the release of the Women's Health Initiative findings, but to what extent
      physicians' and women's concerns about breast cancer contributed to this change
      is unknown. Our study explored physicians' and women's beliefs about hormone
      therapy and breast cancer risk. METHODS: We conducted qualitative in-depth
      interviews with 22 primary care physicians and 45 female patients at two large
      integrated health care delivery systems in Washington State and Massachusetts.
      RESULTS: Concerns about breast cancer risk weighed into the decision-making
      process for physicians and women in initiating and continuing hormone therapy.
      For women, control of menopausal symptoms was important and possibly outweighed
      their concerns about the potential risks of breast cancer. Though concerned about
      its association with increasing breast cancer risk, physicians were willing to
      consider hormone therapy to manage women's menopausal symptoms but were
      frustrated about the lack of available non-hormone therapy alternatives. Most
      physicians and some women were aware of the Women's Health Initiative, and its
      findings appeared to influence their beliefs about hormone therapy and breast
      cancer risk, though doubts remained among both groups about the study findings
      and implications. CONCLUSIONS: Our qualitative study suggests that after the
      Women's Health Initiative, concerns about breast cancer risk weighed into
      decisions to initiate and continue hormone therapy for both physicians and women,
      but menopausal symptoms often directed use.

PMID- 19753505
TI  - Recurrent job loss and mental health among women.
AB  - Growing instability in the labor market has led to an increase in recurrent job
      loss, which primarily affects women (Tamir, 2007). Numerous studies have shown
      that job loss is a stressful, traumatic experience that has consequences for the
      individuals who are laid off. However, few studies have examined how recurrent
      job loss affects individuals. The present study of 134 Israeli women aged 30-45
      years aimed to examine how recurrent job loss affected individual women's
      perceptions of the event and the extent to which it generated emotional stress
      and psychiatric symptoms. Most of the women perceived job loss as a challenging
      event and their assessments of job loss had a stronger impact on the development
      of mental health consequences than did the number of times they had actually been
      laid off. The more the women perceived job loss as threatening, the more they
      reported emotional stress and psychiatric symptoms. Conversely, the more they
      perceived job loss as challenging, the lower their levels of emotional stress.
      Never-married women were laid-off more, and they reported more mental health
      symptoms following recurrent job loss than did married women. The findings
      suggest that perception of job loss as a threatening event might cause mental
      health problems as results of lay-off.

PMID- 19753506
TI  - Mood, dietary restraint, and women's smoking and eating urges.
AB  - Women may have difficulty maintaining smoking cessation efforts due to negative
      affect and fear of weight gain. Dieting smokers who rely on cigarettes for affect
      regulation and weight management may be especially prone to weight gain and
      smoking relapse following initial smoking abstinence. The present study, which
      included 82 women smokers, assessed the relationship between dieting status, self
      efficacy, and temptation to smoke and eat following a depressing or elating mood
      induction. Women with high levels of dietary restraint (i.e., more dieting
      behavior) had more confidence in their ability to refrain from smoking when in
      the elated mood condition, and they were more tempted to smoke when in the
      depressed condition. At low levels of dietary restraint (i.e., less dieting
      behavior), depressed or elated mood condition appeared to have little impact on
      women's confidence to refrain from smoking or their temptation to smoke. Dieting
      status seems to moderate the impact of positive and negative mood states,
      especially with respect to women's smoking behavior. These findings may have
      implications for dieters who are trying to quit smoking and also maintain their
      weight.

PMID- 19753507
TI  - Vaginal hygiene practices and perceptions among women in the urban Northeast.
AB  - To inform development of an intervention to decrease vaginal douching among
      Latinas, we conducted a survey of 335 women aged 16-45 years in primary care
      offices in the urban Northeast, including many Hispanic women (59.7%). About a
      third (30.7%) indicated that they had never douched. Of women who had ever
      douched (n = 235), 51.1% indicated they no longer douche. Women reported using a
      variety of products for douching and non-douching hygiene, including U.S.-made
      and imported commercial products as well as traditional products. Compared to
      Black women, more Hispanic women reported never douching and use of imported
      products. More positive beliefs about the benefits of douching and its safety
      were reported by women who currently douche. Health care providers should be
      aware that women may be using imported and traditional products, the safety of
      which is unknown. Advice about douching from health care providers may be
      effective for some women in helping them choose to stop or not initiate the
      practice.

PMID- 19753508
TI  - Singaporean women's knowledge of human papillomavirus (HPV) and attitudes toward
      HPV vaccination.
AB  - With a vaccination program currently planned to protect Singaporean women from
      human papillomavirus, a need arises for assessing Singaporean women's knowledge
      of human papillomavirus and attitudes toward human papillomavirus vaccination to
      identify barriers to a successful program and to help inform health education
      campaigns. A representative sample of 2,145 women aged between 18 and 49 years
      were randomly selected from households throughout Singapore and interviewed with
      a similar questionnaire to that used in a recent study of Australian women.
      Although Singaporean women's knowledge of human papillomavirus was poor, with
      only 20% having heard of it, attitudes toward human papillomavirus vaccination
      were generally positive. The most trusted sources of information about human
      papillomavirus and vaccination were gynecologists and general practitioners.
      Based on our findings, an urgent need exists in Singapore for accurate and
      accessible information about human papillomavirus and the benefits of
      vaccination.

PMID- 19753509
TI  - [The efficacy of outpatient client-centered psychotherapy for bulimia nervosa:
      results of a randomised controlled trial].
AB  - The efficacy of outpatient client-centered psychotherapy (CCP) for bulimia
      nervosa was investigated using guided self help (GSH) as comparison group. In the
      initial CCP-group ( N=29), 27,6% still met the diagnostic criteria at end of
      treatment and 34,5% at follow-up. In the completer sample ( N=25), 16% met the
      diagnostic criteria at end of treatment and 0% at follow-up; significant
      improvements in eating behaviour, comorbid and general psychopathology could be
      demonstrated which persisted over the follow-up period and which, in part, were
      significantly superior to the improvements in the GSH-group. As regards the
      diagnostic criteria, the CCP proved to be significantly more effective than the
      GSH for both the ITT and the completer samples. At follow-up, this group
      difference was present in the completer samples only. The results provide initial
      evidence for the efficacy of CCP in the outpatient treatment of women with
      bulimia nervosa.

PMID- 19753510
TI  - [Psychodynamic hypothesis about suicidality in elderly men].
AB  - Old men are overrepresented in the whole of all suicides. In contrast, only very
      few elderly men find their way to specialised treatment facilities. Elderly
      accept psychotherapy more rarely than younger persons. Therefore presentations on
      the psychodynamics of suicidality in old men are rare and mostly casuistical. By
      means of a stepwise reconstructable qualitative case comparison of five randomly
      chosen elderly suicidal men with ideal types of suicidal (younger) men concerning
      biography, suicidal symptoms and transference, psychodynamic hypothesis of
      suicidality in elderly men are developed. All patients came into psychotherapy in
      a specialised academic out-patient clinic for psychodynamic treatment of acute
      and chronic suicidality. The five elderly suicidal men predominantly were living
      in long-term, conflictuous sexual relationships and also had ambivalent
      relationships to their children. Suicidality in old age refers to lifelong
      existing intrapsychic conflicts, concerning (male) identity, self-esteem and a
      core conflict between fusion and separation wishes. The body gets a central role
      in suicidal experiences, being a defensive instance modified by age and/or
      physical illness, which brings up to consciousness aggressive and envious
      impulses, but also feelings of emptiness and insecurity, which have to be warded
      off again by projection into the body. In transference relationships there are on
      the one hand the regular transference, on the other hand an age specific turned
      around transference, with their counter transference reactions. The chosen
      methodological approach serves the systematic finding of hypotheses with a higher
      degree in evidence than hypotheses generated from single case studies.

PMID- 19753511
TI  - [Do people with mobbing experience which apply for medical rehabilitation have a
      peculiar personality?].
AB  - Recently results find that victims of mobbing place themselves apart because of
      their personality types. This study deals with the question whether a difference
      between victims of mobbing and those non victims can be determined as far as
      depression, fear and personality type is concerned. METHODS: Anonymous
      questionnaires including anxiety-, depression- and personalityscales were sent to
      1 000 insured whose application for medical rehabilitation had been granted.
      RESULTS: 25% of the applicants felt they had been mobbed. 60% of the victims
      suffered from psychic disorders. The values for depression and anxiety and the
      mark in the personality scale were significantly high. DISCUSSION: Mobbing is a
      relatively common problem for patients in rehabilitation which has to be taken
      seriously. Although it can not be resolved which direction has to be taken by
      judging cause and effect. It should be checked if there is enough support during
      medical rehabilitation for the victims of mobbing.

PMID- 19753512
TI  - [The impact of day nursery in early childhood on psyche in younger adulthood].
AB  - The influence of day nursery in early childhood on later mental and social
      development has been controversially discussed for a long time. Opponents of day
      nurseries express the considerable concern that serious negative mental
      consequences in later life result from early separation from the mother. A sample
      of n=383 respondents (54.2% women, aged 34.2 years on average) from the twenty
      first wave of the Saxony Longitudinal Study (2007) was analyzed regarding the
      impact of day nursery in early childhood on different psychological indicators
      measured later. By applying standardized instruments several aspects were
      examined such as anxiety, depression, the occurrence of common somatic symptoms,
      attachment, confidence towards the future, experiences of menace, and common
      values towards political aspects. The findings show various gender differences,
      e. g. women report a worse mental health. Yet, only one of the examined
      indicators can be explained by day nursery in early childhood: respondents who
      had not been in day nursery felt more threatened by potential stressful life
      events, e. g. unemployment. Furthermore the analysis of variance indicates some
      interaction effects between gender and day nursery in early childhood. Data
      doesn't support the critic that day nursery in early childhood negatively
      influences mental health at a later age. A particular positive impact of day
      nursery in early childhood on the examined aspects cannot be assumed, either.
      Facing the ongoing political debate on the expansion of day nursery facilities,
      further research is needed focusing more in detail on qualitative aspects of day
      nursery.

PMID- 19753513
TI  - Effects of streptozotocin-induced diabetes and elevation of plasma FFA on
      ceramide metabolism in rat skeletal muscle.
AB  - Ceramide is likely to mediate in induction of insulin resistance. The aim of the
      present study was to examine the effect of streptozotocin-diabetes and treatment
      with heparin on ceramide metabolism in skeletal muscles. The experiments were
      performed on Wistar rats divided into three groups: 1) control, 2) treated with
      streptozotocin, and 3) treated with heparin. Assays were carried out on three
      types of muscle: slow-twitch oxidative (soleus), fast-twitch oxidative
      glycolytic, and fast-twitch glycolytic (red and white section of the
      gastrocnemius, respectively). The activity of serine palmitoyltransferase (SPT),
      neutral and acid sphingomyelinase (nSMase and aSMase), and neutral and alkaline
      ceramidase (nCDase and alCDase) was examined. The content of ceramide,
      sphinganine, sphingosine, and sphingosine-1-phosphate was also measured. Both
      streptozotocin-diabetes and treatment with heparin increased the activity of SPT
      in each type of muscle. Heparin inhibits the activity of aSMase and concomitantly
      induces the activity of nSMase in each studied muscle. Streptozotocin decreased
      aSMase activity in each muscle and increased nSMase activity in the soleus and
      red section of the gastrocnemius. Heparin induced, whereas streptozotocin
      inhibited the activity of n-CDase in the soleus and the red section of the
      gastrocnemius. Heparin increased the activity of alCDase in the red
      gastrocnemius. In the soleus and the white gastrocnemius the activity of alCDase
      decreased. Streptozotocin significantly increased the content of ceramide in each
      muscle studied and heparin did it only in the soleus. It is concluded that
      insulin deficiency is accompanied by alterations in ceramide metabolism in
      skeletal muscles. Increased concentration of the plasma free fatty acids may
      mediate certain effects of insulin deficiency.

PMID- 19753514
TI  - [The German version of the Inventory of Stigmatizing Experiences (ISE)--a new
      tool for assessing the prevalence and impact of "felt stigma"].
AB  - OBJECTIVES: Stigma research has been criticized for excluding the views of those
      exposed to stigmatizing reactions. While this changed with the advent of
      qualitative research into stigma, population-based data on the prevalence,
      severity and consequences of stigma experiences are lacking. The present study
      aims at field-testing the German version of the Inventory of Stigmatizing
      Experiences (ISE) , developed to investigate the epidemiology of "felt stigma".
      METHODS: The ISE is a semi-structured questionnaire composed of two scales: one
      measuring the scope of stigma experienced in different life domains (SES; 9
      items), the other assessing their psychosocial impact (SIS; 7 items). The
      instrument was translated into German, using the three-step procedure proposed by
      WHO (translation, back-translation, feasibility testing). Field-testing of the
      German version was carried out on 95 service users. RESULTS: The German version
      of the ISE shows good reliabilities for both the stigma experiences (SES; alpha =
      0.74) and stigma impact (SIS; alpha = 0.86) scales. 54.4 % of service users
      report stigma experiences across the SES; 72 % of these are recent and thus
      susceptible for interventions. CONCLUSIONS: The German version of the ISE is a
      compact and reliable tool for measuring the prevalence and impact of felt stigma,
      with potential uses in both population-based stigma research and clinical
      practice.

PMID- 19753515
TI  - Inappropriate implantable cardioverter-defibrillator therapy: many causes and
      many possible solutions.

PMID- 19753516
TI  - The brain-heart connection: implications for understanding sudden unexpected
      death in epilepsy.
AB  - Epilepsy is one of the commonest neurological problems worldwide. Approximately
      3% of the general population will suffer from epilepsy at some point in their
      lives. Unfortunately, individuals with epilepsy are at a higher risk of death
      than the general population, and sudden unexpected death in epilepsy (SUDEP) is
      the most important direct epilepsy-related cause of death. Information concerning
      risk factors for SUDEP is conflicting, but potential risk factors include young
      age, early onset of epilepsy, duration of epilepsy, uncontrolled seizures,
      seizure frequency, antiepileptic drug number and winter temperatures. Although
      the cause of SUDEP is still unknown, its most commonly suggested mechanisms are
      cardiac abnormalities during and between seizures. As the anatomical substrate of
      epileptic activity in the central nervous system shows a direct relation to
      cardiovascular alterations, this may suggest that patients with epilepsy
      associated with focal central nervous system lesions may face a particular risk
      of SUDEP. Currently, experimental and clinical data supports the importance of
      specific brain structures in the behavioural manifestation, the initiation and
      the propagation of seizures. Regarding the above findings, our research group
      focused on this review article that SUDEP could be related to the occurrence of
      specific brain structure dysfunction or anatomical change, at least in some
      cases.

PMID- 19753517
TI  - Impaired renal function in acute myocardial infarction.
AB  - Impaired renal function is a risk factor for cardiovascular disease and an
      adverse prognostic factor in patients with established cardiovascular disease. In
      addition, with current widespread use of invasive procedures in the treatment of
      acute myocardial infarction, contrast-induced nephropathy is a growing problem in
      this patient population. In acute myocardial infarction, impaired renal function
      may result from underlying kidney disease, acute renal failure, and the effect of
      drugs and contrast agents used during diagnostic procedures or treatment. These
      various causes may coexist, resulting in significantly worse outcomes. Prompt
      recognition of the degree of renal function impairment and institution of
      appropriate preventive and therapeutic measures are among major goals of in
      hospital management of these patients. A commonly used method to evaluate renal
      function is the determination of glomerular filtration rate. Appropriate
      nephroprotective treatment should be used in patients at risk of contrast-induced
      nephropathy. The most commonly used methods include the use of iso-osmotic
      contrast agents and appropriate hydration in the periprocedural period. Studies
      are currently under way to evaluate nephroprotective properties of other drugs
      such as N-acetylcysteine, sodium chloride and sodium bicarbonate solutions,
      mannitol, and statins. Results of some studies suggest that these measures may
      effectively reduce the number of renal function deterioration events in patients
      with acute myocardial infarction. Regardless of the cause, impaired renal
      function in acute myocardial infarction is a significant adverse prognostic
      factor. Thus, despite some inconsistent views regarding the optimal management
      strategy, intensive diagnostic, preventive, and therapeutic measures are clearly
      necessary in patients with acute myocardial infarction and impaired renal
      function.

PMID- 19753518
TI  - The relationship between cardiovascular risk estimated by use of SCORE system and
      intima media thickness and flow mediated dilatation in a low risk population.
AB  - BACKGROUND: The SCORE system is a simple, currently recommended method of
      cardiovascular risk assessment. The aim of this study is to determine the
      relationship between SCORE risk and intima media thickness (IMT) and flow
      mediated dilatation (FMD) in a low risk population. METHODS: 119 people (59 men)
      without known cardiovascular disease and estimated by means of SCORE system risk
      < 5%, were included in the study. The ultrasound method was used to assess
      brachial artery diameter (BAd), FMD, nitroglycerin mediated dilatation (NMD) of
      brachial artery and IMT of common carotid. FMD x BAd and FMD/NMD indexes
      representing hyperemia-induced vasodilatation independent of brachial artery
      properties were analyzed. RESULTS: IMT measured was 0.52 +/- 0.08 mm; FMD: 17.5
      +/- 7.8%; NMD: 27.0 +/- 9.0%; FMD x BAd: 58.2 +/- 22.4, FMD/NMD: 0.64 +/- 0.19.
      Independent predictor for both FMD and NMD was BAd (R(2) -0.31; p < 0.001; R(2) 
      0.44; p < 0.001; respectively), for FMD x BAd index and FMD/NMD index was IMT
      (R(2) -0.04; p = 0.02; R(2) -0.04; p = 0.015) in a multivariate analysis. Risk
      estimated by use of the SCORE system was between 0 and 4% (median-1, 25-75 Q: 0
      2). A relationship between SCORE risk and IMT (ANOVA p < 0.001), FMD (ANOVA p <
      0.001), NMD (ANOVA p < 0.001), FMD x BAd index (ANOVA p = 0.017), but not FMD/NMD
      index (ANOVA p = 0.27), was found. CONCLUSIONS: The association of a simple
      stratifying scale (SCORE system) with indices of early vascular remodeling in a
      low risk population supports its clinical significance.

PMID- 19753519
TI  - Coronary artery visualization using a 64-row multi-slice computed tomography in
      unselected patients with definite or suspected coronary artery disease: a
      comparison with invasive coronary angiography.
AB  - BACKGROUND: Multi-slice computed tomography (MSCT) is becoming an increasingly
      acknowledged means of visualizing coronary arteries. The accuracy of 64-MSCT is
      still a subject of clinical evaluation. Our study, performed with a 64-slice
      scanner, was intended to assess the concordance of coronary artery lumen
      visualization in MSCT and invasive coronary angiography (ICA), both in post
      revascularization and previously medically treated patients. METHODS: We examined
      data from 73 patients (31 women, 42 men, mean age 59 years) referred to our
      hospital in 2006 and 2007 who underwent MSCT and subsequent ICA. Twenty two
      patients had a history of previous revascularization. Of the remaining 51
      patients with intermediate coronary artery disease probability, the indication
      for 64-MSCT was suspicion of coronary artery disease. MSCT coronary angiography
      was performed with Aquilion 64 scanner (Toshiba, Japan). We evaluated 15 segments
      of four native coronary arteries (RCA, LM, LAD and Cx in all patients plus 11
      arterial and 22 venous conduits). The cut-off value for significant stenosis was
      the lumen cross section area reduction exceeding 50%, regardless of segment.
      RESULTS: Regarding native arteries, MSCT and ICA findings were coherent in 80.8%
      of all patients, 93.8% of vessels, and 98.4% of segments. MSCT coronary stent
      patency evaluation was 90.9% correct. The by-pass grafts evaluation was entirely
      concordant in both methods. The respiratory and heart rate variability artifacts
      hindered the MSCT analysis in ten patients (13.7%). The artifacts occurrence in
      misinterpreted studies was nearly two-fold higher than in those that were
      coherent (21.4% vs. 11.9%). CONCLUSIONS: We concluded that a reliable evaluation
      of the coronaries by means of 64-MSCT is feasible both in patients with suspected
      coronary artery disease and those with definite coronary artery disease who had
      previous coronary intervention. Patient selection and co-operation is necessary
      to avoid respiratory and heart rate variability artifacts that may hinder
      analysis.

PMID- 19753520
TI  - Distortion of the QRS in elderly patients with myocardial infarction.
AB  - BACKGROUND: Distortion of the terminal portion of the QRS in the initial
      electrocardiogram (ECG) is a strong predictor of adverse outcome in myocardial
      infarction. Our purpose is to assess the relationship of distortion of QRS and
      other ECG characteristics with older age. METHODS AND RESULTS: We analysed 634
      consecutive patients (age 62.6 +/- 13.7, 77% male) admitted in the first 12 hours
      of ST-elevation myocardial infarction. Two groups of age were defined: < 75 years
      old and >or= 75 years-old. Additionally, we defined two ECG groups according to
      the presence of ST segment elevation with distortion of the terminal portion of
      the QRS in two or more adjacent leads (QRS+) or the absence of this pattern (QRS
      ). Older people had more often QRS+ (30% vs. 20%, p = 0.023). The older group
      with QRS+ had an in-hospital mortality of 18%, vs. 7% with QRS- (p = 0.04), and
      an incidence of major adverse events of 40% vs. 14% (p = 0.002). In the
      multivariate analysis, age >or= 75 years was an independent predictor of
      distortion of the QRS (odds ratio 2.1, 1.2-4.9, p = 0.016). CONCLUSIONS: The
      distortion of the terminal portion of the QRS in myocardial infarction is more
      frequent in elderly people, and is significantly related to adverse prognosis.
      This ECG finding can be helpful to promptly stratify the risk in elderly
      patients.

PMID- 19753521
TI  - Correlation between CD34+ and exercise capacity, functional class, quality of
      life and norepinephrine in heart failure patients.
AB  - BACKGROUND: A previous study associated CD34(+) levels with NYHA functional class
      in heart failure patients. The aim of this study was to correlate CD34(+) levels
      to exercise capacity, functional class, quality of life and norepinephrine in
      heart failure patients. METHODS: Twenty three sedentary patients (52 +/- 7 years,
      78% male) answered the Minnesota Living with Heart Failure Questionnaire and
      rested for 20 minutes before an investigator collect a blood sample. After this,
      patients performed a cardiopulmonary exercise test to determine the heart rate at
      anaerobic and ventilatory threshold and oxygen consumption at peak effort, at
      anaerobic and ventilatory threshold. One other blood sample was collected during
      the peak effort to investigate the norepinephrine and CD34(+) levels. RESULTS:
      Rest percentage of CD34(+) did not show correlation with: left ventricle ejection
      fraction (r = 0.03, p = 0.888), peak VO(2) (r = 0.32, p = 0.13), VO(2) at
      anaerobic threshold (VO(2)AT) (r = 0.03, p = 0.86), VO(2) at ventilatory
      threshold (VO(2)VT) (r = 0.36, p = 0.08), NYHA functional class (r = -0.2, p =
      0.35), quality of life (Minnesota) (r = -0.17, p = 0.42). CD34(+) did not show
      correlation, either, with: peak VO(2) (r = 0.38, p = 0.06), VO(2)AT (r = 0.09, p
      = 0.65), VO(2)VT (r = 0.43, p = 0.4), NYHA functional class (r = -0.13, p=0.54),
      quality of life (r = 0.00, p = 0.99). CONCLUSIONS: CD34(+) levels did not
      correlate with exercise capacity, functional class, quality of life and
      norepinephrine. Percentage of CD34(+) levels did not increase during the
      cardiopulmonary exercise test in heart failure patients.

PMID- 19753522
TI  - Inappropriate cardioverter-defibrillator discharge continues to be a major
      problem in clinical practice.
AB  - BACKGROUND: The purpose of this study was to determine the rate and causes of
      inappropriate rhythm detection, and to compare adequacy of ventricular arrhythmia
      detection by single-chamber and dual-chamber cardioverter-defibrillators (ICD).
      METHODS: We evaluated 190 patients (age 57.2 +/- 11.2 years) with ICD. FOLLOW-UP:
      34.3 +/- +/- 22 months. Dual-chamber ICD was used in 54 patients. RESULTS: We
      evaluated 2244 arrhythmia events recognized as of ventricular origin, including
      ventricular tachycardia and ventricular fibrillation. 431 events (19.2%) were
      recognized erroneously and resulted in an inappropriate ICD discharge. Most cases
      of inappropriate therapies (182 events, 42.23%) were due to atrial fibrillation
      or flutter. Overall, inappropriate arrhythmia detection was found in 64 (33.6%)
      of 190 patients. In terms of the number of affected patients, the most common
      cause of inappropriate ICD discharge was sinus tachycardia - 23 (12.1%) patients,
      followed by atrial fibrillation - 16 (8.4%) patients. Among 54 patients with dual
      chamber ICD, inappropriate therapy was noted in 21 (38.8%) patients, (T wave
      oversensing, sinus tachycardia and atrial fibrillation etc.). No significant
      difference was seen in the rate of inappropriate therapy due to a rapid
      supraventricular rhythm between patients with single-chamber versus dual-chamber
      ICD. In contrast, patients with single-chamber ICD more often experienced
      inappropriate therapy due to atrial fibrillation (155 vs. 28 patients) and sinus
      tachycardia (66 vs. 9 patients). CONCLUSIONS: Despite of introduction of new
      generations of ICDs, the problem of inappropriate ICD discharge could not be
      eliminated. The major problem is distinction between supraventricular arrhythmia
      and ventricular tachyarrhythmia.

PMID- 19753523
TI  - Assessment of left ventricle diastolic function in myocardial infarction patients
      treated with primary angioplasty.
AB  - BACKGROUND: More than 5% of patients over the age of 65 have been found to
      develop heart failure, and over half of them preserve normal left ventricular
      systolic function. In the last few years, diastolic heart failure has become a
      serious clinical and epidemiological problem. METHODS: This prospective study was
      carried out on 99 patients. Patients were evaluated up to three months after
      primary percutaneous coronary intervention (PCI). Evaluation was performed three
      times: within the first 24 hours after primary PCI, on day seven after PCI and at
      three months after PCI. We analyzed the relationship between the severity of left
      ventricle diastolic dysfunction and atherosclerosis risk factors, infarction
      site, maximum levels of cardiac biomarkers such as troponin I, CPK and CK-MB, CRP
      protein levels, angioplasty effectiveness, reperfusion time, TIMI and TMPG grade.
      RESULTS: Most patients with ST elevation myocardial infarction (STEMI) treated
      with primary PCI demonstrated left ventricle diastolic dysfunction on the first
      day of myocardial infarction. Levels of cardiac biomarkers were significantly
      higher in patients with restrictive filling pattern. The inflammatory response
      (CRP levels) was found to have an important role in the development of diastolic
      abnormalities. There was a close relationship between diastolic and systolic
      function. Average values of left ventricular ejection fraction in patients with
      restrictive filling pattern were significantly lower than in those with impaired
      relaxation (44.7 vs. 52.7%; p < 0.001) and normal filling (54.2%; p = 0.002).
      CONCLUSIONS: More than half of patients with a first STEMI have left ventricle
      diastolic dysfunction within the first day after PCI, and these abnormalities are
      still present three months after PCI. Time and effectiveness of reperfusion, CRP
      level, troponin I, max, CPK max and CK-MB max levels as well as left ventricular
      ejection fraction have an important influence on the development of diastolic
      dysfunction. Infarct extension contributes significantly to the process.

PMID- 19753524
TI  - Cardiac myxomas: short- and long-term follow-up.
AB  - BACKGROUND: Cardiac myxomas are the most frequently encountered benign
      intracardiac tumors, that, if left untreated, are inexorably progressive and
      potentially fatal. Patients with cardiac myxoma can be treated only by surgical
      removal. This study summarizes our experience over 22 years with these tumors.
      METHODS: Fifty seven patients (M/F: 14/43, age: 57.9 +/- 14.6 years) with cardiac
      myxomas underwent surgical resection at our institution. There were 82.4% left
      atrial myxomas, 14.0% right atrial myxomas, 3.6% biatrial myxomas. The duration
      of symptoms prior to surgery ranged from 6 to 1,373 days (median 96 days). The
      surgical approach comprised complete wide excision. The diagnostic methods,
      incidence of thromboembolic complications, valve degeneration, surgical repair
      techniques, recurrence and re-operation were reviewed and the Kaplan-Meier
      survival curve was calculated. RESULTS: There were no in-hospital deaths.
      Hospital stay amounted to a mean of 13.7 +/- 6.9 days. Late follow-up was
      available for 54 (94.7%) patients for a median 7.5 years after surgery (23 days
      to 21.4 years). Fifty two patients are alive, while five patients had died after
      a mean interval of 6.3 years. Cause of death was cardiac in 40% of the patients
      (n = 2) and non-cardiac in the other 60% (n = 3). CONCLUSIONS: Surgical excision
      of cardiac myxoma carries a low operative risk and gives excellent short-term and
      long-term results. Surgical excision of the tumor appears to be curative, with
      few recurrences at long-term follow-up. After diagnosis, surgery should be
      performed urgently, in order to prevent complications such as embolic events or
      obstruction of the mitral orifice. Follow-up examination, including
      echocardiography, should be performed regularly.

PMID- 19753525
TI  - Sinus of Valsalva aneurysm.
AB  - Bicuspid aortic valve is one of the most common congenital cardiac anomalies and
      it may be accompanied by other cardiovascular anomalies. Sinus of Valsalva
      aneurysm is a rare anomaly in adult population, but it coexists with bicuspid
      aortic valve quite often. This report describes a 57 years-old patient who had a
      bicuspid aortic valve accompanied by unruptured Valsalva sinus aneurysm with
      significant left anterior narrowing and who underwent successful surgery with
      ascending aorta and aortic valve replacement as well as coronary by-pass
      grafting.

PMID- 19753526
TI  - Acute myocardial infarction in a patient with hemophilia A and factor V Leiden
      mutation.
AB  - Factor VIII:C, epsilon amino-caproic acid or tranexamic acid are prophylactic
      agents used in preventing hemorrhage pre-operatively in patients with hemophilia
      A. Although hemophilia A seems to be a factor that avoids the development of
      acute myocardial infarction (AMI) as it tends to be associated with increased
      bleeding, it should be kept in mind that prothrombotic agents used pre
      operatively for prophylaxis may increase the risk for AMI in the presence of the
      factor V Leiden mutation. In this report, we discuss the development of AMI
      following the use of recombinant factor VIII and tranexamic acid for prophylaxis
      in a patient with known hemophilia before a tooth extraction in conjunction with
      the relevant literature.

PMID- 19753527
TI  - Clinical manifestations of slow coronary flow from acute coronary syndrome to
      serious arrhythmias.
AB  - Slow coronary flow is an angiographic phenomenon characterized by delayed
      opacification of vessels in the absence of any evidence of obstructive epicardial
      coronary disease. In this article, we present serious clinical manifestations of
      extremely slow coronary flow in two hypertensive patients with preserved ejection
      fraction in echocardiographical examination: a 57 year-old woman with acute
      coronary syndrome and temporary ST elevation; and a 65 year-old man with atrial
      tachycardia which was leading to sudden arrest of circulation. The woman was
      admitted to hospital due to recurrent syncope and chest pain. Because of severe
      bradycardia, an AAI pacemaker was implanted. Coronary angiography without evident
      obstructive lesion revealed extremely slow flow of dye through arteries. The man
      was admitted to hospital because of heart palpitations (paroxysmal atrial
      tachycardia, PAT) followed by chest pain. During hospitalization, a sudden arrest
      of circulation in the course of supraventricular tachycardia of 220/min with
      atrioventricular conduction of 1:1 occurred. Coronary arteriography did not show
      any occlusions in the coronary arteries, although extremely slow dye flow was
      seen. Electrophysiological examination revealed arrhythmia of the left atrial
      (PAT) (tricuspid valve anulus mapping) without induced ventricular arrhythmia.
      Because of symptomatic bradyarrhythmia, a VVI heart pacemaker was implanted. Over
      a 12-month observation, his heart rate remained under control, and the patient
      did not complain of chest pains or heart palpitations.

PMID- 19753528
TI  - Transpulmonary closing of left internal mammary artery to pulmonary artery
      fistula with polytetrafluoroethylene covered stent: a case report and review of
      literature.
AB  - Internal mammary artery (IMA) to pulmonary vasculature fistula is a rare
      condition that can be congenital or associated with coronary artery bypass
      grafting surgery (CABG), trauma, inflammation, or neoplasia. This complication
      may cause myocardial ischemia. CABG with an IMA conduit accounts for most
      iatrogenic cases, thus this problem may be encountered more in the future as the
      number of patients undergoing CABG and redo-CABG increases. The natural history
      of IMA-to-pulmonary artery (PA) fistulas is unknown and therefore optimal
      treatment remains controversial. We describe a case of left IMA-to-PA fistula
      treated with balloon expandable covered stent with a transpulmonary approach, and
      we review previously reported cases.

PMID- 19753529
TI  - Multiple shocks after upgrade of an implantable cardioverter-defibrillator to a
      cardiac resynchronization therapy-defibrillator device.
AB  - Inappropriate shocks from implantable cardioverter-defibrillators (ICDs) may
      occur for many reasons. Inappropriate shocks are not simply painful
      inconveniences for patients; they also may result in the need for further
      operative procedures, and sometimes even death. Herein, we report the case of a
      patient who after upgrade of an ICD to a cardiac resynchronization therapy
      defibrillator device (CRT-D), returned with multiple shocks due to altered
      sensing and defibrillation polarities that resulted from actual physical reversal
      of the distal (-) and proximal (+) lead terminals in the header of the device.

PMID- 19753530
TI  - Tension pneumopericardium after removal of pericardiocentesis drainage catheter.
AB  - This image showed tension pneumopericardium caused by removing the
      pericardiocentesis catheter, which was inserted to drain malignant pericardial
      effusion. Tension pneumopericardium is a rare and potentially fatal event.
      Mortality from tension pneumopericardium can be as high as 50%. Therefore, it is
      important to suspect and detect early, if the patient complained of dyspnea after
      removing the pericardiocentesis drainage catheter.

PMID- 19753531
TI  - Electrocardiographical clues to a mechanism of pre-syncope.

PMID- 19753532
TI  - Virtual echocardiography repository for collaboration, sharing and learning.

PMID- 19753533
TI  - Is there a role for digoxin in atrial fibrillation without heart failure?
AB  - Digoxin remains one of the most frequently prescribed drugs in the management of
      atrial fibrillation. The main indications for digoxin in atrial fibrillation are
      restoration of sinus rhythm, prevention of recurrence and slowing of the
      ventricular rate. However, none of these effects of digoxin have been confirmed
      in placebo controlled studies. In addition, recent reports suggest increased
      mortality in patients with atrial fibrillation without heart failure taking
      digoxin. The aim of this article is to review the role of digoxin in atrial
      fibrillation without heart failure.

PMID- 19753534
TI  - History of cardiopulmonary resuscitation.

PMID- 19753535
TI  - Congenital heart disease, exercise capacity and B-type natriuretic peptide.

PMID- 19753537
TI  - Expression of somatostatin receptor subtypes in human pituitary adenomas --
      immunohistochemical studies.
AB  - BACKGROUND: The highly variable expression of SSTR subtypes in pituitary adenomas
      (PA) may partially explain why the subgroup of somatotropinomas or other adenomas
      do not respond to the therapeutic action of currently used long-acting
      somatostatin analogues like octreotide or lanreotide. MATERIAL AND METHODS: Our
      study summarizes the data on expression of all somatostatin receptor subtypes
      (SSTR 1-5), extended for 2A and 2B SSTR isoforms, revealed by means of
      immunohistochemistry in dependence to different hormonal phenotype of the tumour.
      RESULTS: The pattern of SSTR immunostaining (estimated according to the
      percentage frequency of appearance) was in acromegaly: SSTR 5 > SSTR 1 > SSTR 2A
      = SSTR 3 > SSTR 2B, in prolactinomas: SSTR 2B = SSTR 3 = SSTR 5 > SSTR 1 = SSTR
      2A, in gonadotropinomas: SSTR 3 > SSTR 2B > SSTR 1 = SSTR 2A > SSTR 5, in
      corticotropinomas: SSTR 2A > SSTR 1 = SSTR 3 > SSTR 5 > SSTR 2B. In PA
      immunonegative for pituitary hormones, we noticed only a weak staining of all
      receptor subtypes including SSTR 4. In plurihormonal adenomas with positive GH
      phenotype the staining pattern was: SSTR 5 > SSTR 1 = SSTR 2B and in
      plurihormonal PA with negative GH phenotype: SSTR 1 = SSTR 5 > SSTR 2A = SSTR 2B
      = SSTR 3. In plurihormonal adenoma with ACTH immunopositivity, the staining
      pattern was: SSTR = SSTR 2A = SSTR 3 = SSTR 5. SSTR 1 and SSTR 5 were the most
      frequent subtypes of somatostatin receptor in plurihormonal adenomas without ACTH
      expression. CONCLUSIONS: Human PA represents a group of tumours with a much more
      differentiated appearance of somatostatin receptor subtypes. It is very important
      to determine the SSTR profile individually for each tumour to make an appropriate
      decision as to therapeutic strategy choice. Apart from applying SSTR 2 and SSTR 5
      preferring octreotide and lanreotide - newly synthesized multiligand analogues,
      such as SOM 230, KE 108, or other SST selective analogues, may represent a
      further useful approach for the treatment, especially in cases other than
      somatotropinoma or thyrotropinoma.

PMID- 19753538
TI  - Thyroid hormones and the interrelationship of cortisol and prolactin: influence
      of prolonged, exhaustive exercise.
AB  - BACKGROUND: This study examined how prolonged, exhaustive exercise affects: (1)
      thyroid hormones, and (2) the interrelationship of cortisol and prolactin
      responses to such exercise on thyroid hormones. MATERIAL AND METHODS: Male
      subjects performed a treadmill run at their individual ventilatory threshold
      until exhaustion. Blood samples were taken before exercise at rest, baseline
      (BL), at exhaustion (EXH), 30-60-90-minutes into recovery (30 mR, 60 mR, 90 mR),
      and 24-hours into recovery from exercise (24 hR). Blood was analyzed for free
      T(3) (fT(3)), free T(4) (fT(4)), thyroid-stimulating hormone (TSH), cortisol and
      prolactin. RESULTS: ANOVA analysis revealed that at EXH all hormones were
      increased (p < 0.01) from BL levels. At 30 mR and 60 mR the thyroid hormones had
      decreased and returned to BL levels; however, cortisol and prolactin remained
      significantly increased (p < 0.05). At 90 mR all hormones were not different from
      BL levels. By 24 hR, cortisol, fT(3) and TSH were decreased from BL (p < 0.05).
      Correlations revealed EXH cortisol responses were related to the 24 hR TSH
      responses (rs = -0.69, p < 0.01). In addition, EXH cortisol and 24 hR fT(3)
      responses were related (rs = -0.51, p < 0.02). Furthermore, the EXH prolactin and
      TSH responses were related (r(s) = +0.56, p < 0.01), and the 30 mR prolactin
      responses were related to the EXH TSH responses (r(s) = +0.43, p < 0.05).
      CONCLUSIONS: Exhaustive exercise; (1) decreases select thyroid hormones by 24
      hours into recovery, (2) cortisol responses are inversely related to these
      thyroid reductions, and (3) prolactin responses (increases) are directly related
      to TSH changes.

PMID- 19753539
TI  - Effect of opium on glucose metabolism and lipid profiles in rats with
      streptozotocin-induced diabetes.
AB  - BACKGROUND: This experimental study was performed to determine the impact of
      opium use on serum lipid profile and glucose metabolism in rats with
      streptozotocin-induced diabetes. MATERIAL AND METHODS: To determine the effect of
      opium, 20 male rats were divided into control (n = 10) and opium-treated (n = 10)
      groups. After diabetes induction, the animals were investigated for daily glucose
      measurements for 35 days. Serum lipid profile and haemoglobin A1c (HbA(1c)) were
      assayed at the baseline (before induction of diabetes) and at 35-day follow-up.
      RESULTS: The glycaemia levels in the rats treated with opium were similar to the
      levels measured in the control rats (544.8 +/- 62.2 mg/dl v. 524.6 +/- 50.0
      mg/dl, P = 0.434). In addition, there was no difference between the opium-treated
      rats and control rats in HbA(1c) (6.5 +/- 0.5% v. 6.6 +/- 0.2%, P = 0.714).
      Compared to the control rats, the serum total cholesterol, high density
      lipoprotein (HDL), triglyceride and lipoprotein (a) in the test animals were
      similar. CONCLUSION: Opium use has no significant effect on glucose metabolism
      and serum lipid profile in rats with induced diabetes.

PMID- 19753540
TI  - [Occurrence of androgen receptor gene CAG trinucleotide sequence polymorphism in
      the metropolitan population of Polish men].
AB  - BACKGROUND: The activity of androgen receptor (AR) is modulated by a polymorphic
      region located within exon 1 its gene and characterizing a variable number of
      trinucleotide CAG repeats. The length of polymorphic region is inversely
      correlated with the transactivation function of AR gene. It was showed an ethnic
      differences existence in the length CAG repeats of AR gene. The aim of the study
      was determined of the number CAG repeats AR gene occurrence in the population
      Polish men. MATERIAL AND METHODS: In the population-based cross-sectional study
      participated a population-based sample randomly selected 466 men aged 25-65 years
      -- residents of Wroclaw, Poland. The CAG polymorphism was amplified by PCR
      method. RESULTS: The range of androgen receptor CAG repeats was from 1 to 57 with
      a mean 24 +/- 7,68. The most frequent repeat was 21. It was indicated in 34
      (7,3%) of examined subjects. The number of triplets <or= 20 had 137 (29,4%) men
      and > 20 329 (70,6%) men. There were no differences in the length of CAG repeats
      among the age groups. Both the distribution of small (<or= 20) and large (> 20)
      number CAG repeats and age structure in men groups with the longer and shorter
      alleles were statistically all the same. CONCLUSIONS: The average number of AR
      gene CAG repeats and its range in the population Polish men were larger in
      comparison to the west European populations and more reminded the number repeats
      distribution meeting among Asians. This ethnic differences might explain the
      biological variabilities among different populations and another risk of hormone
      dependent diseases occurrence.

PMID- 19753541
TI  - [The incidence of the thyroid microsomal autoantibodies in Alzheimer disease].
AB  - BACKGROUND: Alzheimer disease is associated with degeneration of brain by
      deposition of beta-A4 amyloid protein. Above protein is a product of amyloid
      protein precursor proteolysis. This protein is coded by chromosom 21 together
      with histocompatibility antigens on surface of thyroid follicle. Until now the
      study suggest coexistence of autoimmune thyroid disease and Alzheimer disease.
      The aim of the study was evaluation of thyroid autoantibodies in Alzheimer
      disease. MATERIAL AND METHODS: Study were performed in 34 Alzheimer disease
      patients. Sera of control subjects were obtained from 20 patients with vascular
      dementia. Incidence of thyroid autoantibodies was assessed by polyacrylamide
      electrophoresis gel and western-blotting. Thyroid microsomes were obtained from
      human thyroid tissues by ultracentrifugation and solubilization in 1%
      desoxycholic acid. RESULTS: In 21 sera from 34 we detected autoantibodies against
      thyroid microsomal antigens reacting with 91 kDa antigen. 16 sera were reacting
      with 97 kDa, 13 sera with 55 kDa, and 7 sera with 67 kDa proteins. CONCLUSIONS:
      In sera of Alzheimer disease patients autoantibodies against thyroid microsomal
      antigens can be frequently detected. The most frequent are antibodies against 91
      kDa. It is important to note that Alzheimer disease patients should be screen for
      thyroid hormones.

PMID- 19753542
TI  - [Echocardiographic assessment of myocardial function in patients with type 2
      diabetes].
AB  - BACKGROUND: According to the data obtained from the country-wide NATPOL III
      research, the prevalence of diabetes in Poland stands at 5,6% The objective of
      the work was to assess the heart function of patients with type 2 diabetes by
      means of echocardiography. MATERIAL AND METHODS: 106 patients were examined: 44
      people with type 2 diabetes (gr D) and 62 healthy subjects, constituting the
      control group (gr C). Using the criteria of diabetes control, the first group was
      divided into 2 subgroups: 17 patients with controlled diabetes (gr cD) and 27
      patients with uncontrolled diabetes (gr uD). Next, 2 subgroups were formed
      according to the duration of the disease: 23 patients suffering from diabetes
      >or= 10 years (gr mD) and 21 people suffering from diabetes < 10 years (gr lD).
      The examinations of the patients included electrocardiography and assessments of
      myocardial size and contractibility and diastolic activity of the left ventricle.
      RESULTS: The echocardiographic examination revealed statistically significant
      differences between the groups D and C, between the groups mD, lD, and C, and
      between the groups cD, uD, and C. Moreover, group D additionally exhibited
      positive linear dependences between the duration of the disease and the diastolic
      interventricular septum thickness and between the duration of the disease and the
      mass index of the left ventricle. CONCLUSIONS: Myocardial differences observed in
      the echocardiographic image of a diabetic compared to a healthy person suggest
      myocardial dysfunction caused by diabetes. The existing differences between the
      group with controlled diabetes and the group with uncontrolled diabetes indicate
      that development of organic complications in diabetic patients can only be slowed
      down with procedures to normalise carbohydrate and lipid metabolic parameters and
      the arterial blood pressure.

PMID- 19753543
TI  - [Cognitive aspects of women's body image and eating disorders].
AB  - BACKGROUND: The authors presents basics of theoretical knowledge connected with
      cognitive aspects women's body image in Poland. The authors also presents results
      of research connected with the same subject. MATERIAL AND METHODS: The study
      involved 111 women divided into groups - adolescents and young women and women
      with eating disorders (anorexia and bulimia nervosa). The study methods included
      the Contour Drawing Rating Scale (CDRS) by Thompson and Gray. RESULTS AND
      CONCLUSIONS: The statistical tests indicate differences in the cognitive
      dimension of body image (between ideal and real self) among adolescent and young
      women, and women with eating disorders.

PMID- 19753544
TI  - [Hormonal regulation of feeding].
AB  - Obesity is an important healthcare problem. Steady increase in its prevalence is
      observed worldwide. The underlying cause of obesity is mainly increased calories
      intake. The regulation of appetite is held by the hypothalamus. Satiety signals
      are sent to central nervous system via vagus due to distension of the walls of
      digestive tract and secretion of cytokine signaling after meal digestion.
      Additionally leptin excreted from adipose tissue reflects the state of energy
      storage and affects the hypothalamus. The study presents the literature on
      hormonal regulation of feeding.

PMID- 19753545
TI  - [Obesity and the relationship between somatotrophic axis and bone tissue].
AB  - In postmenopausal obese women often is observed increase bone mineral density in
      relation to slim women. Dominate the view that positive influence of adipose
      tissue on state of skeleton in postmenopausal women can be consequence of the
      boost to load carrying bone, may also result from the role of adipose tissue as
      endocrine organ. Interaction existence between somatotrophic axis and bone tissue
      suggests that revealing itself changes of constituents concentration of this axis
      in obesity individuals may have significance in bone tissue remodeling
      modification after menopause. It has been demonstrated that GH and IGF-I
      secretion decrease with age and this changes are major in obesity persons,
      particularly in women, and they depend on BMI and the percentage of body fat
      content. GH as well as IGF-I may directly and indirectly modulate bone
      remodeling, stimulating both bone formation and bone resorption. In the light of
      latest data this last effect is realized through their influence on expression of
      OPG and/or RANKL, cytokines belonging to the family of tumor necrosis factor
      alpha, which provide important controlling process element of the numbers of
      activated osteoclasts through osteoblasts.

PMID- 19753546
TI  - [Management of Graves' orbitopathy. Comments on the EUGOGO consensus statement].

PMID- 19753547
TI  - [Adrenal disorders in pregnancy].
AB  - Pregnancy dramatically affects the function of the adrenal glands and is
      associated with altered levels of adrenal hormones. Endocrine adaptation to
      pregnancy involves changes in the activities of the hypothalamic-pituitary
      adrenal and renin-angiotensin-aldosterone axes. As a result, pregnancy may
      influence the course of pre-existing adrenal diseases or lead to their unmasking.
      Although disorders of the adrenal glands are rare during pregnancy, they may pose
      a serious health problem. The fact that some symptoms of adrenal disorders may be
      erroneously interpreted as symptoms of normal pregnancy together with overlapping
      their biochemical features make diagnosis of adrenal disorders in pregnancy
      difficult. Antenatal diagnosis and correct treatment of these disorders is
      necessary to prevent maternal and fetal morbidity and mortality. The aim of this
      paper is provide a scientific understanding of the normal function of adrenal
      glands in pregnancy and to discuss the pathophysiology, clinical manifestation,
      diagnosis and management of various adrenal disorders during pregnancy. We
      provide the reader with some practical recommendations concerning the approach to
      pregnant women with adrenal disturbances.

PMID- 19753549
TI  - 1alpha,25-Dihydroxyvitamin D(3) triggered vitamin D receptor and farnesoid X
      receptor-like effects in rat intestine and liver in vivo.
AB  - 1alpha,25-Dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), a natural ligand of the
      vitamin D receptor (VDR), was found to increase the rat ileal Asbt and bile acid
      absorption. The effects of VDR, whose expression is low in liver, on hepatic
      transporters and enzymes are unknown. Protein and mRNA levels of target genes in
      the small intestine, colon and liver after intraperitoneal dosing of
      1,25(OH)(2)D(3) (0-2.56 nmol/kg/day for 4 days) to the rat were determined by
      Western blotting and qPCR, respectively. The 1,25(OH)(2)D(3) treatment increased
      total Cyp3a protein and Cyp3a1 mRNA expressions in the proximal small intestine,
      and the short heterodimer partner (SHP), the fibroblast growth factor 15 (FGF15),
      organic solute transporter (Ostalpha and Ostbeta) mRNA and Asbt protein
      expressions in the ileum. About 50% higher portal bile acid concentration (65.1+/
      14.9 vs 41.9+/-7.8 microm, p<0.05) and elevated expressions of the hepatic
      farnesoid X receptor (FXR) and SHP mRNA resulted with 1,25(OH)(2)D(3) treatment.
      Increased Bsep and Ostalpha mRNA expressions in liver and a>50% reduction in the
      Cyp7a1 protein level (p<0.05) and cholesterol metabolism in rat liver microsomes
      (p=0.002), likely consequences of the bile acid-FXR-SHP cascade and activation of
      the signaling pathway for Cyp7a1 inhibition by FGF15, were found. Increased
      hepatic multidrug resistance-associated protein (Mrp3) and multidrug resistance
      protein 1a (Mdr1a) mRNA and P-gp protein were also observed. It was concluded
      that the changes in hepatic transporters and enzymes in the rat were indirect,
      secondary effects of the liver FXR-SHP cascade due to increased intestinal
      absorption of bile acids and elevated levels of FGF15, events that led to the
      activation of FXR.

PMID- 19753552
TI  - A mechanistic study on the fragmentation of peptide-derived Amadori products.
AB  - Gas phase fragmentation of peptide-derived Amadori products was investigated
      using synthetic compounds regioselectively deuterated as well as labeled with 18O
      at aminofructose moiety. The eliminated molecule CH2O contains exclusively
      protons attached to carbon C6 of the aminofructose moiety. The hydrogen atoms
      connected with the carbon C1 of the aminofructose moiety are partially eliminated
      as a component of water molecules during the dehydration process and partially
      dislocated within the fragmented peptide molecule. The labeled oxygen atom
      attached to the carbon C2 is eliminated in 100% along with the first loss of
      water. The MS3 experiments revealed that the product ion formed by triple
      dehydration of the Amadori product does not eliminate the formaldehyde molecule.
      On the basis of these observations we proposed a hypothetical mechanism of
      Amadori products' fragmentation.

PMID- 19753553
TI  - Surface-activated chemical ionization and cation exchange chromatography for the
      analysis of enterotoxin A.
AB  - Surface-activated chemical ionization (SACI) has been widely used in recent years
      for the analysis of different compounds (e.g. peptides, street drugs, amino
      acids). The main benefits of this technology are its high sensitivity and its
      effectiveness under different chromatographic conditions [i.e. ion exchange
      chromatography and reversed-phase (RP) chromatography]. Here we used SACI in
      conjunction with quadrupole time-of-flight mass spectrometry to analyze
      enterotoxin A, which is produced by Staphylococcus aureus, in milk matrix using
      both RP and ion exchange chromatographies. SACI had increased sensitivity as
      compared with electrospray ionization. Moreover, the higher quantitation
      efficiency of this technique, mainly in terms of limit of detection (0.01 ng/ml),
      limit of quantitation (0.05 ng/ml), linearity range (0.05-50 ng/ml), matrix
      effect, accuracy (intraday and interday accuracy errors were 9.2% and 10.3%,
      respectively) and precision (intraday and interday precision errors were 5.3% and
      12.8%, respectively), is shown and discussed.

PMID- 19753554
TI  - Transition metals as electron traps. II. Structures, energetics and electron
      transfer dissociations of ternary Co, Ni and Zn-peptide complexes in the gas
      phase.
AB  - Transition metal cations Co2+, Ni2+ and Zn2+ form 1 : 1 : 1 ternary complexes
      with 2,2'-bipyridine (bpy) and peptides in aqueous methanol solutions that have
      been studied for tripeptides GGG and GGL. Electrospray ionization of these
      solutions produced singly charged [Metal(bpy)(peptide-H)]+ and doubly charged
      [Metal(bpy)(peptide)]2+ ions (Metal = metal ion) that underwent charge reduction
      by glancing collisions with Cs atoms at 50 and 100 keV collision energies.
      Electron transfer to [Metal(bpy)(peptide)]2+ ions was less than 4.2 eV exoergic
      and formed abundant fractions of non-dissociated charge-reduced intermediates.
      Charge-reduced [Metal(bpy)(peptide)]+ ions dissociated by the loss of a hydrogen
      atom, ammonia, water and ligands that depended on the metal ion. The Ni and Co
      complexes mainly dissociated by the elimination of ammonia, water, and the
      peptide ligand. The Zn complex dissociated by the elimination of ammonia and bpy.
      A sequence-specific fragment was observed only for the Co complex. Electron
      transfer to [Metal(bpy)(peptide-H)]+ was 0.6-1.6 eV exoergic and formed
      intermediate radicals that were detected as stable anions after a second electron
      transfer from Cs. [Metal(bpy)(peptide-H)] neutrals and their anions dissociated
      by the loss of bpy and peptide ligands with branching ratios that depended on the
      metal ion. Optimized structures for several spin states, electron transfer and
      dissociation energies were addressed by combined density functional theory and
      Moller-Plesset perturbational calculations to aid interpretation of experimental
      data. The experimentally observed ligand loss and backbone cleavage in charge
      reduced [Metal(bpy)(peptide)]+ complexes correlated with the dissociation
      energies at the present level of theory. The ligand loss in +CR- spectra showed
      overlap of dissociations in charge-reduced [Metal(bpy)(peptide-H)] complexes and
      their anionic counterparts which complicated spectra interpretation and
      correlation with calculated dissociation energies.

PMID- 19753555
TI  - Time-dependent effects of Klebsiella pneumoniae endotoxin on the pharmacokinetics
      of chlorzoxazone and its main metabolite, 6-hydroxychlorzoxazone, in rats:
      restoration of the parameters in 96 hour in KPLPS rats to control levels.
AB  - It has been reported that chlorzoxazone (CZX) was primarily metabolized via
      hepatic Cyp2e1 to form 6-hydroxychlorzoxazone (OH-CZX) in rats, and the activity
      of aniline hydroxylase (a Cyp2e1 marker) in the liver was significantly decreased
      in rats at 24 h after pretreatment with lipopolysaccharide derived from
      Klebsiella pneumoniae (24 h KPLPS rats), whereas the levels were not changed at 2
      h and 96 h in the KPLPS rats. Thus, the time-dependent pharmacokinetic parameters
      of CZX and OH-CZX were evaluated after the intravenous administration of CZX (20
      mg/kg) to control rats, and the 2 h, 24 h and 96 h KPLPS rats along with the time
      dependent changes in the protein expression of hepatic Cyp2e1. After the
      intravenous administration of CZX to 24 h KPLPS rats, the AUC(0-2 h) of OH-CZX
      and AUC(OH-CZX, 0-2 h)/AUC(CZX) were significantly smaller (by 40.5% and 71.2%,
      respectively) than those of controls due to the significant decrease (by 75.3%)
      in the protein expression of hepatic Cyp2e1. However, in 96 h KPLPS rats, the
      pharmacokinetic parameters of both CZX and OH-CZX were unchanged compared with
      controls due to the restoration of the protein expression of hepatic Cyp2e1 to
      control levels. These observations highlighted the existence of the time
      dependent effects of KPLPS on the pharmacokinetics of CZX and OH-CZX in rats.

PMID- 19753557
TI  - Exposure response--getting the dose right.

PMID- 19753562
TI  - Synthesis and cytotoxic evaluation of 6-(3-pyrazolylpropyl) derivatives of 1,4
      naphthohydroquinone-1,4-diacetate.
AB  - Several new 6-(3-pyrazolylpropyl) derivatives of 1,4-naphthohydroquinone-1,4
      diacetate (NHQ-DA) have been prepared by chemical modifications of the Diels
      Alder adduct of alpha-myrcene and 1,4-benzoquinone. All these new compounds and
      precursors have been evaluated in vitro for their cytotoxicity against cultured
      human cancer cells of MB-231 breast-adeno carcinoma, A-549 lung carcinoma, and HT
      29 colon carcinoma. GI(50) values ranged in and below the micromolar
      concentration level.

PMID- 19753563
TI  - Synthesis and in-vitro activity of 4'-modified analogues of ddA as potent anti
      HIV agents.
AB  - This paper reports the synthesis of novel 4'-hydrophobic pocket deoxythreosyl C
      nucleosides. The key threose-like intermediates 9 and 14 were constructed from
      acyclic ketone derivatives, respectively. The antiviral activities of the
      synthesized compounds against the HIV-1, HSV-1, HSV-2, and HCMV viruses were
      evaluated. The 9-deaza-adenine derivatives 10 and 20 showed good anti-HIV
      activity without exhibiting significant cytotoxicity.

PMID- 19753564
TI  - Synthesis and biological evaluation of 2-mercapto-1,3-benzothiazole derivatives
      with potential antimicrobial activity.
AB  - The enhancement of bacterial resistance of pathogens to currently available
      antibiotics constitutes a serious public health threat. So, intensive efforts are
      underway worldwide to develop new antimicrobial agents. To identify compounds
      with a potent antimicrobial profile, we designed and synthesized low molecular
      weight 2-mercaptobenzothiazole derivatives 2a-2l and 3a-3l. Both series were
      screened for in-vitro antibacterial activity against the representative panel of
      Gram-positive and Gram-negative bacteria strains. The biological screening
      identified compounds 2e and 2l as the most active ones showing an interesting
      antibacterial activity with MIC values of 3.12 microg/mL against Staphylococcus
      aureus and 25 microg/mL against Escherichia coli, respectively. The replacement
      of the S-H by the S-Bn moiety resulted in considerable loss of the antibacterial
      action of the 3a-3l series. The antibiotic action of compounds 2e and 2l was also
      investigated by testing their activity against some clinical isolates with
      different antimicrobial resistance profile. Moreover, the involvement of the NorA
      efflux pump in the antibacterial activity of our molecules was evaluated.
      Finally, in this paper, we also describe the cytotoxic activity of the most
      interesting compounds by MTS assay against HeLa and MRC-5 cell lines.

PMID- 19753565
TI  - Bone manganese as a biomarker of manganese exposure: a feasibility study.
AB  - BACKGROUND: There is a need for a diagnostic tool with the ability to measure
      cumulative exposure to manganese (Mn) in the workplace. Measuring bone Mn levels
      with in vivo neutron activation analysis (IVNAA) could serve as a biomarker of
      past exposure. Bone Mn levels of welders were measured and compared to the levels
      found in subjects without exposure to the element. METHOD: Forty subjects (30
      welders and 10 controls) were recruited. An occupational history was obtained and
      subjects underwent IVNAA bone Mn measurements. RESULTS: The mean bone Mn levels
      were (2.9 +/- 0.4) and (0.1 +/- 0.7) microg Mn/g Ca for welders and controls,
      respectively (P < 0.05). CONCLUSIONS: This project, the first of its kind,
      reports differences in bone Mn between Mn-exposed welders and non-occupationally
      exposed subjects. It appears that bone Mn levels do reflect differences in the
      occupational exposure of welders.

PMID- 19753566
TI  - Depressive symptoms and atypical jobs in France, from the 2003 Decennial health
      survey.
AB  - BACKGROUND: The objective is to study the relations between depressive symptoms
      and atypical jobs in the working population in France and to determine if these
      associations might be linked with psychosocial and organizational constraints.
      METHODS: The data come from the 2003 Decennial health survey and concern 11,895
      workers. Depressive symptoms were measured by the CES-D scale. Atypical jobs were
      defined by employment status (fixed-term or temporary job contract, permanent job
      contract, self-employed) and by part-time work during working life (involuntary
      or chosen). Working conditions related to atypical hours and psychosocial factors
      were also studied. RESULTS: For both sexes, involuntary part-time work was
      associated with a higher frequency of depressive symptoms, but part-time work by
      choice was not. Fixed-term contracts were associated with depressive symptoms
      only in women. All of these associations persisted after adjustment for
      psychosocial and organizational factors. CONCLUSION: The associations between
      atypical jobs and depressive symptoms differ for job status according to sex and
      do not seem to be associated with the worst psychosocial working conditions. The
      interpretation of these results is nonetheless limited in part by the cross
      sectional nature of the survey.

PMID- 19753567
TI  - Training future hospitalists with simulators: a needed step toward accessible,
      expertly performed bedside procedures.

PMID- 19753568
TI  - Use of simulation-based mastery learning to improve the quality of central venous
      catheter placement in a medical intensive care unit.
AB  - BACKGROUND: Central venous catheter (CVC) insertions are performed frequently by
      internal medicine residents. Complications, including arterial puncture and
      pneumothorax, decrease when operators use fewer needle passes to insert the CVC.
      In this study, we evaluated the effect of simulation-based mastery learning on
      CVC insertion skill. DESIGN: This was a cohort study of internal jugular (IJ) and
      subclavian (SC) CVC insertions by 41 internal medicine residents rotating through
      the medical intensive care unit (MICU) over a five-month period. Thirteen
      traditionally-trained residents were surveyed about the number of needle passes,
      complications, and procedural self-confidence on CVCs inserted in the MICU.
      Concurrently, 28 residents completed simulation-based training in IJ and SC CVC
      insertions. Simulator-trained residents were expected to perform CVC insertions
      to mastery standards on a central line simulator. Simulator-trained residents
      then rotated through the MICU and were surveyed regarding CVC placement. The
      impact of simulation training was assessed by comparing group survey results.
      RESULTS: No resident met the minimum passing score (MPS) (79.1%) for CVC
      insertion at baseline: mean (M) (IJ) = 48.4%, standard deviation (SD) = 23.1,
      M(SC) = 45.2%, SD = 26.3. All residents met or exceeded the MPS at testing after
      simulation training: M(IJ) = 94.8%, SD = 10.0, M(SC) = 91.1%, SD = 17.8 (p <
      0.001). In the MICU, simulator-trained residents required fewer needle passes to
      insert a CVC than traditionally-trained residents: M = 1.79, SD = 1.0 versus M =
      2.78, SD = 1.77 (p = 0.04). Simulator-trained residents displayed more self
      confidence about their procedural skills: (M = 81, SD = 11 versus M = 68, SD =
      20, p = 0.02). CONCLUSIONS: Simulation-based mastery learning increased
      residents' skills in simulated CVC insertion, decreased the number of needle
      passes when performing actual procedures, and increased resident self-confidence.

PMID- 19753569
TI  - Risk of venous thromboembolism in hospitalized patients with peripherally
      inserted central catheters.
AB  - BACKGROUND: Peripherally inserted central catheters (PICC) are increasingly used
      in hospitalized patients. The benefit can be offset by complications such as
      upper extremity deep vein thrombosis (UEDVT). METHODS: Retrospective study of
      patients who received a PICC while hospitalized at the Methodist University
      Hospital (MUH) in Memphis, TN. All adult consecutive patients who had PICCs
      inserted during the study period and who did not have a UEDVT at the time of PICC
      insertion were included in the study. A UEDVT was defined as a symptomatic event
      in the ipsilateral extremity, leading to the performance of duplex
      ultrasonography, which confirmed the diagnosis of UEDVT. Pulmonary embolism (PE)
      was defined as a symptomatic event prompting the performance of ventilation
      perfusion lung scan or spiral computed tomography (CT). RESULTS: Among 777
      patients, 38 patients experienced 1 or more venous thromboembolisms (VTEs),
      yielding an incidence of 4.89%. A total of 7444 PICC-days were recorded for 777
      patients. This yields a rate of 5.10 VTEs/1000 PICC-days. Compared to patients
      whose PICC was inserted in the SVC, patients whose PICC was in another location
      had an increased risk (odds ratio = 2.61 [95% CI = 1.28-5.35]) of VTE. PICC
      related VTE was significantly more common among patients with a past history of
      VTE (odds ratio = 10.83 [95% CI = 4.89-23.95]). CONCLUSIONS: About 5% of patients
      undergoing PICC placement in acute care hospitals will develop thromboembolic
      complications. Thromboembolic complications were especially common among persons
      with a past history of VTE. Catheter tip location at the time of insertion may be
      an important modifiable risk factor.

PMID- 19753570
TI  - Does personalized vascular access training on a nonhuman tissue model allow for
      learning and retention of central line placement skills? Phase II of the
      procedural patient safety initiative (PPSI-II).

PMID- 19753571
TI  - Development of a test to evaluate residents' knowledge of medical procedures.
AB  - BACKGROUND AND AIM: Knowledge of core medical procedures is required by the
      American Board of Internal Medicine (ABIM) for certification. Efforts to improve
      the training of residents in these procedures have been limited by the absence of
      a validated tool for the assessment of knowledge. In this study we aimed to
      develop a standardized test of procedural knowledge in 3 medical procedures
      associated with potentially serious complications. METHODS: Placement of an
      arterial line, central venous catheter, and thoracentesis were selected for test
      development. Learning objectives and multiple-choice questions were constructed
      for each topic. Content evidence was evaluated by critical care subspecialists.
      Item test characteristics were evaluated by administering the test to students,
      residents and specialty clinicians. Reliability of the 32-item instrument was
      established through its administration to 192 medical residents in 4 hospitals.
      RESULTS: Reliability of the instrument as measured by Cronbach's alpha was 0.79
      and its test-retest reliability was 0.82. Median score was 53% on a test
      comprising elements deemed important by critical care subspecialists. Increasing
      number of procedures attempted, higher self-reported confidence, and increasing
      seniority were predictors of overall test scores. Procedural confidence
      correlated significantly with increasing seniority and experience. Residents
      performed few procedures. CONCLUSIONS: We have successfully developed a
      standardized instrument to assess residents' cognitive competency for 3 common
      procedures. Residents' overall knowledge about procedures is poor. Experiential
      learning is the dominant source for knowledge improvement, but these experiences
      are increasingly rare.

PMID- 19753572
TI  - Asking for help: internal medicine residents' use of a medical procedure service.
AB  - BACKGROUND: Little is known about the professional help-seeking behavior of
      residents as they perform procedures in the hospital. OBJECTIVE: To determine
      when residents seek formal supervision to perform inpatient medical procedures.
      DESIGN: We conducted a prospective cohort study of resident physicians' use of
      formal supervision through a medical procedure service (MPS) for placing central
      venous catheters (CVCs) and performing thoracenteses. We compared resident,
      procedure, and patient characteristics among MPS and non-MPS procedures. We
      performed bivariable and multivariable analyses to examine factors associated
      with use of the MPS. We also performed a subgroup analysis of non-MPS procedures
      to assess the influence of resident, procedure, and patient characteristics on
      the choice of informal supervision. SETTING: Boston teaching hospital. SUBJECTS:
      Sixty-nine internal medicine residents. MAIN OUTCOME MEASURE: Use of an elective
      MPS for formal faculty supervision. RESULTS: Among 191 procedures performed, 79
      (41%) used the MPS. Residents were more likely to seek faculty supervision via
      the MPS among patients with 3 or more comorbidities (odds ratio [OR], 2.1; 95%
      confidence interval [CI], 1.2-3.5). They were less likely to seek MPS supervision
      when procedures were performed urgently or emergently (OR, 0.4; 95% CI, 0.2-0.8).
      There were few differences in the characteristics of unsupervised and informally
      supervised procedures. CONCLUSIONS: Resident physicians appear to seek formal
      assistance appropriately for procedures they perform on sicker patients.
      Additional research is needed to understand whether overconfidence or poor access
      to attending physicians is responsible for their failure to seek consultation
      with urgent and emergent cases.

PMID- 19753573
TI  - Hospitalist handoffs: a systematic review and task force recommendations.
AB  - BACKGROUND: Handoffs are ubiquitous to Hospital Medicine and are considered a
      vulnerable time for patient safety. PURPOSE: To develop recommendations for
      hospitalist handoffs during shift change and service change. DATA SOURCES: PubMed
      (through January 2007), Agency for Healthcare Research and Quality (AHRQ) Patient
      Safety Network, white papers, and hand search of article bibliographies. STUDY
      SELECTION: Controlled studies evaluating interventions to improve in-hospital
      handoffs (n = 10). DATA EXTRACTION: Studies were abstracted for design, setting,
      target, outcomes (including patient-level, staff-level, or system-level
      outcomes), and relevance to hospitalists. DATA SYNTHESIS: Although there were no
      studies of hospitalist handoffs, the existing literature from related disciplines
      and expert opinion support the use of a verbal handoff supplemented with written
      documentation in a structured format or technology solution. Technology solutions
      were associated with a reduction in preventable adverse events, improved
      satisfaction with handoff quality, and improved provider identification. Nursing
      studies demonstrate that supplementing verbal exchange with a written medium
      leads to improved retention of information. White papers characterized effective
      verbal exchange, as focusing on ill patients and actions required, with time for
      questions and minimal interruptions. In addition, content should be updated daily
      to ensure communication of the latest clinical information. Using this
      literature, recommendations for hospitalist handoffs are presented with
      corresponding levels of evidence. Recommendations were reviewed by hospitalists
      at the Society of Hospital Medicine (SHM) Annual Meeting and by an
      interdisciplinary team of expert consultants and were endorsed by the SHM
      governing board. CONCLUSIONS: The systematic review and resulting recommendations
      provide hospitalists a starting point from which to improve in-hospital handoffs.

PMID- 19753574
TI  - Retrievable vena cava filters: a clinical review.
AB  - Vena cava filters were developed as a method of preventing pulmonary embolism
      (PE) in patients with venous thromboembolism (VTE) at risk for bleeding from
      therapeutic anticoagulation. However, the long-term complications of filter
      placement, such as caval thrombosis, have mitigated some of the benefits,
      particularly in those patients with only a temporary contraindication to
      anticoagulation. Retrievable filters were designed to avoid the long-term risks
      of a permanent filter while still providing short-term protection against PE. As
      a result, their use has expanded from patients with known thrombosis to those
      without VTE who are at high risk for developing PE. In this review, we discuss
      the different types of retrievable filters, indications for their placement,
      complications that can occur during and after placement, and their use as
      prophylaxis in surgical patients. Although the use of retrievable filters in
      patients with known VTE is clear, further studies are needed to establish their
      prophylactic efficacy in the surgical patient. Until this evidence is available,
      we recommend that retrievable filters should be used only in patients with acute
      VTE who are at risk for recurrent thromboembolism and have a transient risk for
      bleeding.

PMID- 19753575
TI  - Improving internal medicine residents' performance, knowledge, and confidence in
      central venous catheterization using simulators.
AB  - BACKGROUND: Efficacy of simulators in teaching central venous catheterization
      (CVC) in an internal medicine residency program is unknown. OBJECTIVE: To
      determine whether or not learning CVC on simulators is associated with
      improvement in performance of CVC, knowledge about the procedure, and self
      reported confidence. METHODS: All consenting first-year internal medicine
      residents who completed training in CVC on simulators were included. Participants
      were evaluated pre- and post-training by video-recorded CVC insertion and
      multiple-choice knowledge assessments. Procedural technique was rated in a
      blinded fashion by two independent adjudicators. Knowledge retention and self
      reported confidence were reassessed at 18 months. MEASUREMENTS: Primary outcome
      of CVC performance was assessed based on global rating score (minimum 1, maximum
      5). Secondary measures include checklist score (out of ten), knowledge score and
      self-reported confidence (6-point Likert scale ranging from "none" to
      "complete"). RESULTS: Median global rating scores in 30 participants increased
      from 3.5 (IQR = 3-4) to 4.5 (IQR = 4-4.5) (P < 0.001). Checklist score increased
      from 9 (IQR = 6-9.5) to 9.5 (IQR = 9-9.5) (P < 0.001). Knowledge score increased
      from 65.7 +/- 11.9% to 81.2 +/- 10.7% (P < 0.001). Confidence increased from 3
      ("moderate", IQR = 2-3) to 4 ("good", IQR=3-4) (P < 0.001). Sixteen participants
      completed the retention tests. Improvement in knowledge score and confidence at
      18 months was retained compared with baseline (P = 0.002 and P < 0.0001
      respectively). CONCLUSIONS: Use of simulators in teaching CVC in an internal
      medicine residency program results in improved procedural performance, knowledge,
      and self-reported confidence. Improvement in knowledge and confidence was
      retained at 18 months.

PMID- 19753576
TI  - Maximal medical therapy and palliative care can work together: when are advanced
      care measures appropriate?

PMID- 19753577
TI  - Elephantiasis nostras verrucosa.

PMID- 19753578
TI  - Trends in catheter ablation for atrial fibrillation in the United States.
AB  - BACKGROUND: There are few data on the use of catheter ablation for atrial
      fibrillation (AF) in the United States. We analyzed data from the National
      Hospital Discharge Survey (NHDS) to examine trends in the rate of catheter
      ablation for hospitalized patients with AF over a 15-year period. OBJECTIVE: To
      examine rates of catheter ablation in patients with AF over time. DESIGN: All
      adult patients in the NHDS with an International Classification of Diseases,
      Ninth Revision, Clinical Modification (ICD-9-CM) code for AF from the years 1990
      to 2005 were identified and assessed for the presence of a cardiac catheter
      ablation procedure code. Clinical characteristics associated with ablation were
      identified and multivariable logistic regression used to determine trends in the
      rate of ablation therapy over time. RESULTS: We identified 269,471 adults with
      AF. The rate of catheter ablation in AF patients increased from 0.06% in 1990 to
      0.79% in 2005 (P < 0.001 for trend). Compared to those not undergoing ablation,
      ablated patients were younger (mean age 66 versus 76 years; P < 0.001), more
      likely to be male (57% versus 43%; P < 0.001), have private insurance (22% versus
      11%; P < 0.001), and have a none of the following stroke risk factors: congestive
      heart failure, hypertension, age >75 years, diabetes mellitus, or
      stroke/transient ischemic attack (37% versus 16%; P < 0.001). Catheter ablation
      in AF patients increased by 15% per year over the time period (95% confidence
      interval [CI], 13%-16%) and across all age groups, including in patients age > or
      =80 years (0.0% in 1990 and 0.26% in 2005; P < 0.001 for trend). CONCLUSIONS: The
      rate of catheter ablation in patients with AF is increasing significantly over
      time, even in the oldest patients. Medicine.

PMID- 19753579
TI  - Laser secondary neutral mass spectrometry for copper detection in micro-scale
      biopsies.
AB  - Disease progression and clinical diagnostics of a number of hereditable metabolic
      diseases are determined by organ involvement in disturbed deposition of certain
      molecules. Current clinical imaging is unable to visualize this maldistribution
      with sufficient specificity and sensitivity, such as in Wilson's disease. The
      quest for understanding cellular Cu distribution in these patients requires
      element- and molecule-specific images with nanometer-scale spatial resolution. We
      have used a new cryo-mass spectrometric instrument with an integrated
      cryosectioning chamber for preparation and analysis of frozen hydrated samples of
      Wilson's disease tissue. With laser post-ionization secondary neutral mass
      spectrometry (laser-SNMS), we were able to image Cu and other intrinsic elements
      and molecules in less than 1 mg of frozen hydrated liver tissue from a murine
      model of Wilson's disease. A 40-50 times higher Cu concentration was measured in
      the disease tissue as compared to the control mouse. Furthermore, major
      histomorphological changes were observed using this advanced nano-science tool.
      The results showed that the combination of in-vacuum cryosectioning and cryo
      laser-SNMS technologies is particularly well suited for identifying specific cell
      structures and imaging trace element concentrations with subcellular resolution
      and upper-parts-per-billion sensitivity in biological samples. This technology
      can provide a novel diagnostic tool for clinical applications in various diseases
      involving trace elements.

PMID- 19753580
TI  - Influence of basic residues on dissociation kinetics and dynamics of singly
      protonated peptides: time-resolved photodissociation study.
AB  - Product ion yields in postsource decay and time-resolved photodissociation at 193
      and 266 nm were measured for some peptide ions with lysine ([KF6 + H]+, [F6K +
      H]+, and [F3KF3 + H]+) formed by matrix-assisted laser desorption ionization. The
      critical energy (E0) and entropy (DeltaS(double dagger)) were determined by RRKM
      fitting of the data. The results were similar to those found previously for
      peptide ions with histidine. To summarize, the presence of a basic residue,
      histidine or lysine, inside a peptide ion retarded its dissociation by lowering
      DeltaS(double dagger). On the basis of highly negative DeltaS(double dagger),
      presence of intramolecular interaction involving a basic group in the transition
      structure was proposed.

PMID- 19753581
TI  - Enhanced end-of-life care associated with deploying a rapid response team: a
      pilot study.
AB  - HYPOTHESIS: Institution of a rapid response team (RRT) improves patients' quality
      of death (QOD). SETTING: A 425-bed community teaching hospital. PATIENTS: : All
      medical-surgical patients whose end-of-life care was initiated on the hospital
      wards during the 8 months before (pre-RRT) and after (post-RRT) actuation. STUDY
      DESIGN: Retrospective cohort study. METHODS: Medical records of all patients were
      reviewed using a uniform data abstraction tool. Demographic information,
      diagnoses, physiologic and laboratory data, and outcomes were recorded. RESULTS:
      A total of 197 patients died in both the pre-RRT and post-RRT periods. There were
      no differences in age, sex, advance directives, ethnicity, or religion between
      groups. Restorative outcomes, including in-hospital mortality (27 vs. 30/1000
      admissions), unexpected transfers to intensive care (17 vs. 19/1000 admissions)
      and cardiac arrests (3 vs. 2.5/1000 admissions) were similar during the 2
      periods. Outcomes, including formal comfort care only orders (68 vs. 46%),
      administration of opioids (68 vs. 43%), pain scores (3.0 +/- 3.5 vs. 3.7 +/-
      3.2), patient distress (26 vs. 62%), and chaplain visits (72 vs. 60%), were
      significantly better in the post-RRT period compared to the pre-RRT period (all P
      < 0.05). During the post-RRT period, 61 patients died with RRT care and 136 died
      without RRT care. End-of-life care outcomes were similar for these groups except
      more RRT patients had chaplain visits proximate to their deaths (80% vs. 68%; P =
      0.0001). CONCLUSIONS: Institution of an RRT in our hospital had negligible impact
      on outcomes of patients whose goal was restorative care. Deployment of the RRT
      was associated with generally improved end-of-life pain management and
      psychosocial care.

PMID- 19753582
TI  - Upper gastrointestinal hemorrhage: have new therapeutics made a difference?
AB  - BACKGROUND: To explore the distribution of etiologies and risk factors of upper
      gastrointestinal hemorrhage (UGH) in the context of new pharmacologic therapies
      that may alter the risk of UGH. METHODS: Retrospective study performed on
      eligible UGH inpatients at 2 academic medical centers, between July 1, 2001 and
      June 30, 2003. Administrative data and chart review were used to identify
      demographics, UGH risk factors, and UGH etiologies. Bivariate and multivariate
      analyses were performed to describe distributions and associations of risk
      factors and etiologies. RESULTS: UGH was identified in 227 subjects, with ED (n =
      99; 44%), peptic ulcer disease (PUD) (n = 75; 33%), and variceal bleeds (n = 39;
      17%) accounting for the majority of bleeds. Known risk factors for UGH occurred
      in 70% (n = 156) of subjects (prior UGH 43% [n = 90], nonsteroidal anti
      inflammatory drug (NSAID) use 23% [n = 52], aspirin [ASA] use 25% [n = 57], NSAID
      + ASA use 6.6% [n = 15]), while 19% (n = 42) were using a proton-pump inhibitor
      (PPI) and 5% (n = 11) a cyclooxygenase-2 (COX-2) inhibitor. Subjects at site 1
      were more likely to have ED (odds ratio [OR], 7.1; P < 0.001) and less likely to
      have variceal bleeding (OR, 0.12; P = 0.009) in multivariate analyses. Preventive
      therapy did not differ between sites. CONCLUSIONS: Unlike older studies, PUD was
      not the most common etiology, suggesting that advances in Helicobacter pylori (H.
      pylori) eradication may affect the epidemiology of UGH. Despite advances in
      therapeutics of acid-related disease, ED accounted for the majority of UGH. Most
      subjects had risk factors for UGH and most were not receiving protective therapy.
      Large between site-differences in the distribution of etiologies existed.

PMID- 19753583
TI  - Medical admission order sets: effective, practical, generalizable--but not
      perfect.

PMID- 19753584
TI  - Optimization of antiviral prescribing for influenza.

PMID- 19753586
TI  - To bleed or not to bleed: what is the factor?

PMID- 19753587
TI  - Ancillary testing in children with rotavirus gastroenteritis.
AB  - OBJECTIVES: Costly microbiological assays are frequently performed in patients
      with rotavirus gastroenteritis (RGE) to exclude concurrent serious bacterial
      infection (SBI). The incidence of concurrent SBI in this population is unknown
      but estimated to be low. The primary objective was to describe the incidence of
      SBI in children with RGE. The secondary objective was to elucidate risk factors
      for prolonged length of stay (LOS) in the cohort. METHODS: All children < or =18
      years seen at a community hospital for laboratory-confirmed RGE over a 4-year
      period were included in a retrospective cohort study to describe the incidence of
      concurrent SBI and to identify risk factors for prolonged LOS. Prolonged LOS was
      defined as hospitalization for > or =3 days. RESULTS: Ninety-four cases of RGE
      were identified; 58 (61.7%) males and 80 (85.1%) African Americans. The median
      age was 8 months (interquartile range [IQR], 1 month to 16 years) and 83 patients
      (88.3%) required admission. There were no cases of SBI. The median LOS was 2
      days. Age < or = 6 months (adjusted odds ratio [OR], 3.0; 95% confidence interval
      [CI], 1.2-7.7; P = 0.022) and collection of a peripheral blood culture (adjusted
      OR, 2.7; 95% CI, 1.0-7.1; P = 0.043) were associated with LOS > or = 3 days.
      CONCLUSIONS: In children evaluated at a community hospital with laboratory
      confirmed RGE, no episodes of SBI occurred. This finding challenges the need to
      perform invasive, costly, microbiological assays to exclude concurrent SBI in
      this population. Children 6 months and younger were at increased risk of
      prolonged hospitalization from RGE.

PMID- 19753588
TI  - Benign pneumatosis intestinalis in a child with cavopulmonary shunt and immune
      thrombocytopenic purpura.
AB  - We present the case of a nine-year-old boy with hypoplastic left heart syndrome
      and immune thrombocytopenic purpura who subsequently developed pneumatosis
      intestinails with a benign clinical examination. While benign pneumatosis
      intestinails is a well-known clinical entity, the alarming radiographic findings
      set off a cascade of clinical angst among many providers. This case reminds
      physicians to correlate the ancillary study results with the patient's clinical
      presentation and stability.

PMID- 19753589
TI  - Pleural effusion associated with pegylated interferon alpha and ribavirin
      treatment for chronic hepatitis C.
AB  - Lung toxicity related to interferon (IFN) alpha typically takes a form of
      interstitial pneumonitis, granulomatous inflammation, or organizing pneumonia. We
      report a case of a 52-year-old woman, who developed pneumonitis with exudative,
      lymphocytic-predominant pleural effusion following treatment with pegylated IFN
      alpha and ribavirin for hepatitis C. Her symptoms and lung findings resolved over
      3 months of observation without corticosteroid therapy.

PMID- 19753590
TI  - Central coordination: answer to the admission bottleneck.

PMID- 19753591
TI  - Risk factors for work-related musculoskeletal disorders: A systematic review of
      recent longitudinal studies.
AB  - OBJECTIVE: This systematic review was designed and conducted in an effort to
      evaluate the evidence currently available for the many suggested risk factors for
      work-related musculoskeletal disorders. METHODS: To identify pertinent literature
      we searched four electronic databases (Cinahl, Embase, Medline, and The Cochrane
      Library). The search strategies combined terms for musculoskeletal disorders,
      work, and risk factors. Only case-control or cohort studies were included.
      RESULTS: A total of 1,761 non-duplicated articles were identified and screened,
      and 63 studies were reviewed and integrated in this article. The risk factors
      identified for the development of work-related musculoskeletal disorders were
      divided and organized according to the affected body part, type of risk factor
      (biomechanical, psychosocial, or individual) and level of evidence (strong,
      reasonable, or insufficient evidence). CONCLUSIONS: Risk factors with at least
      reasonable evidence of a causal relationship for the development of work-related
      musculoskeletal disorders include: heavy physical work, smoking, high body mass
      index, high psychosocial work demands, and the presence of co-morbidities. The
      most commonly reported biomechanical risk factors with at least reasonable
      evidence for causing WMSD include excessive repetition, awkward postures, and
      heavy lifting. Additional high methodological quality studies are needed to
      further understand and provide stronger evidence of the causal relationship
      between risk factors and work-related musculoskeletal disorders. The information
      provided in this article may be useful to healthcare providers, researchers, and
      ergonomists interested on risk identification and design of interventions to
      reduce the rates of work-related musculoskeletal disorders.

PMID- 19753592
TI  - Data linkage to estimate the extent and distribution of occupational disease: new
      onset adult asthma in Alberta, Canada.
AB  - BACKGROUND: Although occupational asthma is a well recognized and preventable
      disease, the numbers of cases presenting for compensation may be far lower than
      the true incidence. METHODS: Workers' Compensation Board (WCB) claims for any
      reason 1995-2004 were linked to physician billing data. New onset adult asthma
      (NOAA) was defined as a billing for asthma (ICD-9 code of 493) in the 12 months
      prior to a WCB claim without asthma in the previous 3 years. Incidence was
      calculated by occupation, industry and, in a case-referent analysis, exposures
      estimated from an asthma specific job exposure matrix. RESULTS: There were
      782,908 WCB eligible claims, with an incidence rate for NOAA of 1.6%: 23
      occupations and 21 industries had a significantly increased risk. Isocyanates (OR
      1.54: 95% CI 1.01-2.36) and exposure to mixed agricultural allergens (OR = 1.59:
      95% CI 1.17-2.18) were related to NOAA overall, as were exposures to cleaning
      chemicals in men (OR = 1.91:95% CI 1.34-2.73). Estimates of the number of cases
      of occupational asthma suggested a range of 4% to about half for the proportion
      compensated. CONCLUSIONS: Data linkage of administrative records can demonstrate
      under-reporting of occupational asthma and indicate areas for prevention.

PMID- 19753593
TI  - Improving insulin ordering safely: the development of an inpatient glycemic
      control program.
AB  - This report describes a Glycemic Control Program instituted at an academic
      regional level-one trauma center. Key interventions included: 1) development of a
      subcutaneous insulin physician order set, 2) use of a real-time data report to
      identify patients with out-of-range glucoses, and 3) implementation of a clinical
      intervention team. Over four years 18,087 patients admitted to non-critical care
      wards met our criteria as dysglycemic patients. In this population, glycemic
      control interventions were associated with increased basal and decreased sliding
      scale insulin ordering. No decrease was observed in the percent of patients
      experiencing hperglycemia. Hypoglycemia did decline after the interventions (4.3%
      to 3.6%; p = 0.003). Distinguishing characteristics of this Glycemic Control
      Program include the use of real-time data to identify patients with out-of-range
      glucoses and the employment of a single clinician to cover all non-critical care
      floors.

PMID- 19753594
TI  - Traumatic occupational injuries in Hispanic and foreign born workers.
AB  - BACKGROUND: Hispanic and foreign-born workers suffer high rates of occupational
      fatality. Reasons for this are not well understood. Our aim was to gather
      information about the details related to severe, non-fatal occupational injuries
      in this vulnerable population. METHODS: Eight years of data were obtained from an
      urban trauma center. In addition, medical consultations of individuals admitted
      for an occupational injury during an 8-month period are reported. RESULTS:
      Hispanics were more highly represented than expected; their number of injuries
      steadily rose. Hispanics were more likely to be injured by machinery and hand
      tools. Workers reported hazardous working conditions, lack of workers
      compensation, short time in current employment, and not working in their usual
      job. CONCLUSION: Trauma systems can provide a glimpse of risk factors for severe
      injuries in vulnerable workers. We recommend greater use of this data source,
      follow backs, long-term follow up of individuals, and improvement of surveillance
      of vulnerable working populations.

PMID- 19753595
TI  - Carbon black and lung cancer-testing a novel exposure metric by multi-model
      inference.
AB  - BACKGROUND: In a recent analysis of a UK cohort Sorahan and Harrington [2007: Am
      J Ind Med 50: 555-564] assessed the most recent 15 years of exposure ("lugging")
      to support their hypothesis that carbon black acts as a late stage lung
      carcinogen. We tested this metric in a German cohort of 1,528 carbon black
      workers. METHODS: We used a multi-model Cox regression approach (720 models) to
      explore the impact of duration and cumulative exposure to carbon black "lugged"
      by 0, 5, 10, 15, and 20 years. This approach covered four sub-cohorts, including
      an inception cohort, different exposure scenarios and varying combinations of
      confounders. RESULTS: Seven hundred nineteen models returned negative
      coefficients. Only one model estimated a small positive, but clearly non
      significant coefficient (P = 0.8). CONCLUSIONS: Despite extensive searching, no
      exposure scenario suggested an adverse effect of "lugged" carbon black exposure
      on lung cancer mortality. Our analysis does not support the hypothesis of carbon
      black being a late stage carcinogen.

PMID- 19753596
TI  - A pilot respiratory health assessment of nail technicians: symptoms, lung
      function, and airway inflammation.
AB  - BACKGROUND: Recent surveys suggest nail technicians, particularly artificial nail
      applicators, have increased respiratory symptoms and asthma risk. METHODS: We
      examined lung function (n = 62) and a marker of airway inflammation, i.e.,
      exhaled nitric oxide (ENO) (n = 43), in a subset of nail technician and control
      participants in a pilot health assessment. RESULTS: Bivariate analysis of
      technicians demonstrated that job latency was inversely correlated with FEV1
      percent predicted (FEV1PP) (r = -0.34, P = 0.03) and FVCPP (r = -0.32, P = 0.05).
      Acrylic gel contact hours were inversely correlated with FEV1PP (r = -0.38, P =
      0.02) and FVCPP (r = -0.47, P = 0.003). Current smoking was inversely and
      significantly (P <or= 0.05) associated with ENO in bivariate analysis. Log 10 ENO
      levels were directly correlated with job latency (P = 0.012) and gel nail
      application (P = 0.026) in multivariable analyses. CONCLUSIONS: These positive
      pilot respiratory test results warrant additional future investigation.

PMID- 19753600
TI  - Effects of extremely low-frequency magnetic field exposure on cognitive
      functions: results of a meta-analysis.
AB  - There is extensive literature on possible effects of extremely low-frequency
      magnetic fields (ELF-MFs) on human cognitive functions. However, due to
      methodological deficits (e.g., low statistical power, small sample sizes)
      findings have been inconsistent. In the current study we try to overcome these
      problems by carrying out a meta-analysis. Literature research revealed 17
      studies. Nine of these were included in the meta-analysis because they fulfilled
      minimum requirements (e.g., at least single-blind experimental study design and
      documentation of means and standard deviation of the dependent variables). All of
      the studies used a 50 Hz magnetic field exposure. Small but significant effect
      sizes could be detected in two cognitive dimensions: in the hard level of visual
      duration discrimination, task-exposed subjects performed better than controls; at
      the intermediate level however, exposed subjects performed worse. Additionally, a
      significant improvement of correct responses was observed in the dimension of
      "flexibility" under exposure. However, due to the small number of studies per
      performance dimensions and the resulting instability of estimates, these findings
      have to be treated with extreme caution. Taken together, the results of the meta
      analysis provide little evidence that ELF-MFs have any effects on cognitive
      functions.

PMID- 19753601
TI  - Oat beta-glucan increases postprandial cholecystokinin levels, decreases insulin
      response and extends subjective satiety in overweight subjects.
AB  - This study recorded acute biochemical and subjective measures of satiety,
      followed by energy intake from a subsequent meal, after varying doses of beta
      glucan in extruded breakfast cereals. Molecular weight, solubility and viscosity
      of beta-glucan products were determined. Seven male and seven female subjects
      (BMI 25-36 kg/m) consumed five breakfasts (different doses of beta-glucan sourced
      from two different technological processes) and dietary intake was measured after
      four hours. Blood was collected to measure glucose, insulin, ghrelin and
      cholecystokinin, and visual analogue scales measured subjective satiety.
      Molecular weight, solubility and viscosity indicated products were likely to
      increase luminal viscosity. beta-Glucan was found to decrease insulin secretion
      over 2 h (RMANOVA, p = 0.011) in a dose responsive manner from 2.16 to 5.68 g per
      serving (p = 0.007). Cholecystokinin levels increased linearly over the same
      range of beta-glucan concentrations (p = 0.002) in women. Subjective satiety was
      increased at a beta-glucan dose of 2.2 g (p = 0.039). Subsequent meal intake
      decreased by greater than 400 kJ with higher beta-glucan dose (>5 g). beta-Glucan
      improves satiety and release of cholecystokinin is likely to be part of the
      mechanism. Products with different sources of beta-glucan provide similar
      benefits but each product requires individual testing.

PMID- 19753602
TI  - Impact of apple polyphenols on GSTT2 gene expression, subsequent protection of
      DNA and modulation of proliferation using LT97 human colon adenoma cells.
AB  - Apple extract (AE) enhances expression of glutathione S-transferases (e.g.,
      GSTT2) in human colon cells (LT97). Therefore, aim of the present study was to
      identify functional consequences of GSTT2 induction by AE and to determine the
      relation of AE effects to isolated compounds. Polyphenol composition of AE was
      analyzed. LT97 cells were treated with AE or synthetic polyphenol mixture (SPM)
      under conditions that induced GSTT2, and challenged with GSTT2-2 substrate cumene
      hydroperoxide (CumOOH) to determine DNA damage using comet assay. Modulation of
      GSTT2 expression (real-time PCR) was reassessed, and the influence on cell
      proliferation and pro-oxidative potential of AE and SPM were assessed to
      understand additional mechanisms. Induction of GSTT2 by AE was accompanied by
      protection of LT97 cells from CumOOH-induced genotoxicity. Although SPM was
      unable to reflect AE-specific bioactivity related to GSTT2 modulation and anti
      genotoxicity, inhibition of LT97 cell proliferation by SPM was comparable.
      Storage of AE caused changes in phenolic composition along with loss of activity
      regarding GSTT2 induction and amplified growth inhibition. At the applied
      concentrations, no H(2)O(2) formation was detectable with any of the substances.
      AE can protect against oxidatively induced DNA damage. Nevertheless,
      chemopreventive effects of AE strongly depend on the specific composition, which
      is modified by storage.

PMID- 19753603
TI  - Formation of hydrogen peroxide in cell culture media by apple polyphenols and its
      effect on antioxidant biomarkers in the colon cell line HT-29.
AB  - Beneficial health effects of diets containing fruits have partly been attributed
      to polyphenols which display a spectrum of bioactive effects, including
      antioxidant activity. However, polyphenols can also exert prooxidative effects in
      vitro. In this study, polyphenol-mediated hydrogen peroxide (H(2)O(2)) formation
      was determined after incubation of apple juice extracts (AEs) and polyphenols in
      cell culture media. Effects of extracellular H(2)O(2 )on total glutathione (tGSH;
      =GSH + GSSG) and cellular reactive oxygen species (ROS) level of HT-29 cells were
      studied by coincubation +/- catalase (CAT). AEs ( > or =30 microg/mL)
      significantly generated H(2)O(2) in DMEM, depending on their composition.
      Similarly, H(2)O(2) was measured for individual apple polyphenols/degradation
      products (phenolic acids > epicatechin, flavonols > dihydrochalcones). Highest
      concentrations were generated by compounds bearing the o-catechol moiety.
      H(2)O(2) formation was found to be pH dependent; addition of CAT caused a
      complete decomposition of H(2)O(2) whereas superoxide dismutase was less/not
      effective. At incubation of HT-29 cells with quercetin (1-100 microM), generated
      H(2)O(2) slightly contributed to antioxidant cell protection by modulation of
      tGSH- and ROS-level. In conclusion, H(2)O(2) generation in vitro by polyphenols
      has to be taken into consideration when interpreting results of such cell culture
      experiments. Unphysiologically high polyphenol concentrations, favoring
      substantial H(2)O(2 )formation, are not expected to be met in vivo, even under
      conditions of high end nutritional uptake.

PMID- 19753604
TI  - Intake of Maillard reaction products reduces iron bioavailability in male
      adolescents.
AB  - The effects of diets with different Maillard reaction products (MRPs) content on
      biological iron utilization were compared using in vitro/in vivo assays. Diets
      were rich (brown diet, BD) or poor (white diet) in MRP. In vitro studies included
      iron solubility after in vitro digestion of diets and iron transport across Caco
      2 cells. In the human assay 18 healthy adolescent males (11-14 years)
      participated in a 2-wk randomized two-period crossover trial. Subjects collected
      urine and faeces on the last 3 days of each dietary period, and fasting blood
      samples were obtained after periods. In vitro dietary iron availability was
      significantly lower with the BD than the white diet (9.52 and 12.92%,
      respectively), as a consequence of the lower iron solubility after the in vitro
      digestion, but not as a result of decreased transport of the remaining soluble
      iron. The BD consumption increased iron fecal excretion ( approximately 1.4-fold)
      and significantly decreased its bioavailability ( approximately 2.7-fold), mainly
      due to the effects found at digestive level. Serum biochemical parameters related
      to iron metabolism remained unaltered. It is concluded the presence of MRP in the
      diet negatively affects iron bioavailability. As iron deficiency may be related
      to learning impairment and to reductions of cognitive and physical functions,
      possible long-term effects of excessive MRP intake during adolescence warrant
      attention.

PMID- 19753605
TI  - Prevention of colon carcinogenesis by apple juice in vivo: impact of juice
      constituents and obesity.
AB  - It is estimated that 75-85% of all chronic diseases are linked to lifestyle
      related and environmental factors. The development of colon cancer is positively
      associated with obesity and inversely associated with the intake of dietary
      fibre, fruit and vegetable. Apple juice is the most widely consumed fruit
      beverage in Germany. It contains a specific spectrum of polyphenols and other
      components that may reduce the risk of colon cancer. Epidemiologic studies
      suggest an inverse correlation between apple consumption and colon cancer risk,
      although the mechanisms for these observations are not clear. The present review
      summarizes the preventive potential of apple juices and different apple
      constituents on biomarkers related to colon carcinogenesis with special focus on
      the in vivo evidence and the cancer promoting condition of obesity. However,
      under the cancer promoting condition of obesity, apple juice did not show cancer
      preventive bioactivity. In our experiments a cancer-preventive bioactivity of
      apple juice is lacking in rats under the cancer-promoting condition of obesity.
      To further investigate, whether this lack of efficacy observed in obese rats
      might be representative for obese individuals human intervention studies on high
      risk groups such as obese or diabetic individuals are of interest and will be
      conducted.

PMID- 19753606
TI  - Identification of 3-hydroxy-beta-damascone and related carotenoid-derived aroma
      compounds as novel potent inducers of Nrf2-mediated phase 2 response with
      concomitant anti-inflammatory activity.
AB  - Structural comparison of apple constituents with known inducers of phase two
      cytoprotective enzymes led to the identification of 3-hydroxy-beta-damascone and
      related carotenoid derived aroma compounds as potent inducers of NAD(P)H:quinone
      reductase (QR) activity. Damascone-related compounds were found to be more potent
      inducers than ionone derivatives, with CD values (concentrations required to
      double the specific activity of QR in Hepa1c1c7 cell culture) in the range of 1.0
      5.7 microM. QR induction by 3-hydroxy-beta-damascone was shown to be mediated via
      transcription factor Nrf2 signaling in transient transfection experiments. We
      further identified aroma compounds as potent inhibitors of LPS-induced inducible
      nitric oxide synthase activity in Raw 264.7 cell culture. Again, damascone
      derivatives were most potent with half-maximal inhibitory concentration values of
      1.8-7.9 microM. These results reveal previously unrecognized cancer
      chemopreventive potential of aroma compounds such as beta-damascenone, 3-hydroxy
      beta-damascone, and related substances, which may contribute to the cancer
      protective efficacy of apple products and other dietary sources in animal models.

PMID- 19753607
TI  - Incorporation and metabolism of punicic acid in healthy young humans.
AB  - The objective of this study was to investigate the incorporation and metabolism
      of punicic acid (PA, cis9,trans11,cis13-18:3) in healthy young humans. The study
      was a randomized controlled trial. After 7 days adaptation with sunflower seed
      kernels supplementation, 30 subjects were then divided into the control and test
      group (n = 15). The test group was supplemented with Trichosanthes kirilowii (TK)
      seed kernels containing 3 g of PA per day in the form of triacylglycerols for 28
      days. The control group was provided with sunflower seed kernels. After
      consumption of TK seeds containing 3 g PA per day for 28 days, the proportion of
      PA was increased from 0.00 to 0.47% in plasma and 0.00 to 0.37% in red blood cell
      membranes (RBCM), respectively. The proportion of cis9,trans11-18:2 was increased
      from 0.05 to 0.23% in plasma and 0.03 to 0.17% in RBCM after 28 days of
      intervention, respectively. Our results suggest that PA can be effectively
      incorporated into human plasma and RBCM, and is also associated with the
      increasing proportion of cis9,trans11-18:2 in humans, presumably as a result of
      metabolism by a saturation reaction. Edible TK seeds could be a potential dietary
      source of conjugated linoleic acids.

PMID- 19753608
TI  - Curcumin reduces oxidative and nitrative DNA damage through balancing of oxidant
      antioxidant status in hamsters infected with Opisthorchis viverrini.
AB  - Opisthorchis viverrini (OV) infection is endemic in northeastern Thailand. We
      have previously reported that OV infection induces oxidative and nitrative DNA
      damage via chronic inflammation, which contributes to the disease and
      cholangiocarcinogenesis. Here, we examined the effect of curcumin, an
      antioxidant, on pathogenesis in OV-infected hamsters. DNA lesions were detected
      by double immunofluorescence and the hepatic expression of oxidant-generating and
      antioxidant genes was assessed by quantitative RT-PCR analysis. Dietary 1.0%
      curcumin significantly decreased OV-induced accumulation of 8-oxo-7,8-dihydro-2'
      deoxyguanosine (8-oxodG), an oxidative DNA lesion, and 8-nitroguanine, a
      nitrative DNA lesion, in the nucleus of bile duct epithelial and inflammatory
      cells. Expression of oxidant-generating genes (inducible nitric oxide synthase;
      iNOS, its nuclear transcriptional factor, NF-kappaB, and cyclooxygenase-2), and
      plasma levels of nitrate, malondialdehyde, and alanine aminotransferase, were
      also decreased in curcumin-treated group. In contrast, curcumin increased the
      mRNA expression of antioxidant enzymes (Mn-superoxide dismutase and catalase),
      and ferric-reducing anti-oxidant power in the plasma. In conclusion, curcumin
      reduced oxidative and nitrative DNA damage by suppression of oxidant-generating
      genes and enhancement of antioxidant genes, leading to inhibition of oxidative
      and nitrative stress. Therefore, curcumin may be used as a chemopreventive agent
      to reduce the severity of OV-associated diseases and the risk of
      cholangiocarcinoma (CCA).

PMID- 19753609
TI  - High sensitivity detection of the glial fibrillary acidic protein as indicator
      for TSE risk material in meat products using an immuno-PCR.
AB  - The emergence of prion diseases in cattle during the bovine spongiform
      encephalopathy (BSE) epidemic and the transmission to humans causing variant
      Creutzfeldt-Jakob disease by consume of BSE-contaminated meat has focused
      attention on the use of tissues from the central nervous system (CNS) in food. To
      avoid food contamination, it is regulated by law that specified risk material has
      to be removed from food chains. Detection of well-expressed CNS indicator
      proteins such as the glial fibrillary acidic protein (GFAP) assumes an important
      role in detection of food contamination; however, the sensitivity of detection
      performed on basis of ELISAs is limited. Consequently, there is an urgent need
      for high-sensitivity detection methods. We describe the development of an immuno
      PCR assay with enhancement of the immunoreaction by amplification of a DNA
      fragment linked to the antigen-antibody complex. This immuno-PCR assay shows
      enhanced sensitivity in GFAP detection of at least two orders of magnitude
      compared to the ELISA technique carried out under identical conditions. The
      immuno-PCR proves to be a suitable tool for the high-sensitivity detection of
      marker proteins in food imported by food chain processes. It is applicable for
      use by food and veterinary facilities, and institutes involved in food
      monitoring.

PMID- 19753610
TI  - GSTT2, a phase II gene induced by apple polyphenols, protects colon epithelial
      cells against genotoxic damage.
AB  - The potential protective effect of a polyphenol-rich diet for colon
      carcinogenesis is of great scientific and medical interest. Apples are a main
      source of polyphenols, and apple juice has been shown to attenuate chemically
      induced colon carcinogenesis in animal models. In addition to an antioxidant and
      antiproliferative activity, apple polyphenols have been shown to elevate
      expression of the phase II gene glutathione S-transferase T2 (GSTT2) in colon
      epithelial cells. We hypothesized that apple polyphenols may thereby provide
      protection against oxidant-induced DNA damage. Using GSTT2 promoter constructs
      and luciferase reporter assays, we found that polyphenolic apple extracts (AE)
      can directly enhance GSTT2 promoter activity. Comet assays demonstrated that the
      genotoxicity of the GSTT2 substrate cumene hydroperoxide (CumOOH) was
      significantly reduced when HT29 colon epithelial cells were pretreated with AE.
      Overexpression of GSTT2 in HT29 cells significantly reduced CumOOH induced DNA
      damage, whereas shRNA mediated knockdown of GSTT2 gene expression resulted in
      higher damage. Our results causally link GSTT2 levels with protection from
      genotoxic stress, and provide evidence that the antigenotoxic effects of apple
      polyphenols in vitro are at least in part due to an induction of GSTT2
      expression. Induction of phase II genes may contribute to primary chemoprevention
      of colon cancer by apple polyphenols.

PMID- 19753611
TI  - Modification of pulse sequences reduces occupational exposure from MRI switched
      gradient fields: Preliminary results.
AB  - The gradient fields in magnetic resonance imaging (MRI) will in some
      circumstances exceed the ICNIRP guidelines of occupational electromagnetic field
      exposure when personnel are near the scanner during MRI scanning. In this work we
      have shown that using commercially available modified sequences for noise
      reduction purposes, exposure will decrease by a factor of 1.5 with preserved
      image quality. This is a first step toward optimizing occupational exposure
      within the scanner room without affecting image quality.

PMID- 19753612
TI  - Awarding of 2008 most influential bioelectromagnetics journal paper by citation
      awards.

PMID- 19753613
TI  - Peak width-mass correlation in CID MS/MS of isomeric oligosaccharides using
      traveling-wave ion mobility mass spectrometry.
AB  - Isomeric oligosaccharides gamma-cyclodextrin (gamma-CD), glucosyl-betaCD (Glc1
      betaCD) and maltosyl-alphaCD (Glc2-alphaCD) were analyzed by traveling-wave ion
      mobility (twIM) mass spectrometry (MS). Their formation of multicharged multimers
      differed from each other. The ion mobility-mass spectrometry was useful in the
      self-assembling and complex formation analyses of CD isomers. The drift times of
      the isomers and their product ions with the same mass were almost the same in
      collision-induced dissociation (CID) MS/MS. In contrast, the ion mobility peak
      widths were sensitive to structural differences of the isomeric product ions. The
      twIM peak width (ms-micros) of the product ions [M-Glc(n) + H]+ (n = 0-6) of
      gamma-CD correlated linearly with their masses (Da); the large and/or long chain
      product ions had wider peak widths, which were much wider than those from the
      general diffusion effect. This was a novel and useful 'trend line' to
      discriminate between the three isomers. Plots of [M-Glc(2-6) + H]+ of Glc1-betaCD
      and [M-Glc(3-6) + H]+ of Glc2-alphaCD product ions' plots were on the same trend
      line as gamma-CD. The plots of [M-Glc1 + H]+ of Glc1-betaCD and [M-Glc(1, 2) +
      H]+ of Glc2-alphaCD strayed from the gamma-CD line; their peak widths were
      narrower than those of gamma-CD. These results indicated that product ions from
      the chemical species of Glc1-beta CD and Glc2-alphaCD retained their CD
      structure. Analyses of the IM peak widths enable us to elucidate the structures
      of the product ions.

PMID- 19753614
TI  - Utilizing hospital discharge data (HD) to compare fatal and non-fatal work
      related injuries among Hispanic workers in New Jersey.
AB  - BACKGROUND: This study explores the utilization of Hospital Discharge (HD) data
      to obtain estimates of work-related non-fatal injuries rates in NJ to determine
      if Hispanics workers have an increased risk of specific work-related injuries. In
      addition, HD data are used to compare the rate ratios between fatal and non-fatal
      injuries in this population to demonstrate the effectiveness of using HD as a
      surveillance tool for monitoring injury trends and performing evaluations.
      METHODS: Several types of fatal and non-fatal injuries were modeled using Poisson
      regression with the following predictor variables: gender, ethnicity, and year.
      The estimated number of workers by ethnicity employed in NJ each year was
      obtained from the U.S. Census Bureau, DataFerrett, Current Population Survey,
      November 2006, a data mining tool which accesses CPS data. RESULTS: These
      analyses, utilizing estimates of working population at-risk, indicate that
      Hispanic workers have an increased risk of four particular work-related injuries
      compared with non-Hispanics, and Hispanics were injured at a younger age than non
      Hispanics. In addition the rankings of the rate ratios from the comparison
      between non-fatal and fatal risk estimates were similar; indicating that
      occupational surveillance of non-fatal injuries is a viable component to be
      considered. CONCLUSIONS: HD data are effective for monitoring trends over time
      across ethnic groups and injury types. Therefore, non-fatal injury surveillance
      should be considered for targeting specific worker populations for interventions
      to reduce exposure to workplace hazards, and can be a valuable surveillance tool
      in efforts to reduce occupational injuries.

PMID- 19753615
TI  - Cell placement and guidance on substrates for neurochip interfaces.
AB  - Interface devices such as integrated planar patch-clamp chips are being developed
      to study the electrophysiological activity of neuronal networks grown in vitro.
      The utility of such devices will be dependent upon the ability to align neurons
      with interface features on the chip by controlling neuronal placement and by
      guiding cell connectivity. In this paper, we present a strategy to accomplish
      this goal. Patterned chemical modification of SiN surfaces with poly-d-lysine
      transferred from PDMS stamps was used to promote adhesion and guidance of cryo
      preserved primary rat cortical neurons. We demonstrate that these neurons can be
      positioned and grown over microhole features which will ultimately serve as patch
      clamp interfaces on the chip.

PMID- 19753616
TI  - Formation of the unusual [M+H-11 Da]+ ion peak in the collision-induced
      dissociation mass spectrum of [M+H]+ ion of hydrochlorothiazide.

PMID- 19753617
TI  - Depression as a predictor of disease progression and mortality in cancer
      patients: a meta-analysis.
AB  - BACKGROUND: Cancer patients and oncologists believe that psychological variables
      influence the course of cancer, but the evidence remains inconclusive. This meta
      analysis assessed the extent to which depressive symptoms and major depressive
      disorder predict disease progression and mortality in cancer patients. METHODS:
      Using the MEDLINE, PsycINFO, CINAHL, and EMBASE online databases, the authors
      identified prospective studies that examined the association between depressive
      symptoms or major/minor depression and risk of disease progression or mortality
      in cancer patients. Two raters independently extracted effect sizes using a
      random effects model. RESULTS: Based on 3 available studies, depressive symptoms
      were not shown to significantly predict cancer progression (risk ratio [RR]
      unadjusted = 1.23; 95% confidence interval [CI], 0.85-1.77; P = .28). Based on
      data from 25 independent studies, mortality rates were up to 25% higher in
      patients experiencing depressive symptoms (RR unadjusted = 1.25; 95% CI, 1.12
      1.40; P < .001), and up to 39% higher in patients diagnosed with major or minor
      depression (RR unadjusted = 1.39; 95% CI, 1.10-1.89; P = .03). In support of a
      causal interpretation of results, there was no evidence that adjusting for known
      clinical prognostic factors diminished the effect of depression on mortality in
      cancer patients. CONCLUSIONS: This meta-analysis presented reasonable evidence
      that depression predicts mortality, but not progression, in cancer patients. The
      associated risk was statistically significant but relatively small. The effect of
      depression remains after adjustment for clinical prognosticators, suggesting that
      depression may play a causal role. Recommendations were made for future research
      to more clearly examine the effect of depression on cancer outcomes.

PMID- 19753618
TI  - Clinical practice patterns and cost effectiveness of human epidermal growth
      receptor 2 testing strategies in breast cancer patients.
AB  - BACKGROUND: Testing technologies are increasingly used to target cancer
      therapies. Human epidermal growth factor receptor 2 (HER2) testing to target
      trastuzumab for patients with breast cancer provides insights into the evidence
      needed for emerging testing technologies. METHODS: The authors reviewed
      literature on HER2 test utilization and cost effectiveness of HER2 testing for
      patients with breast cancer. They examined available evidence on: percentage of
      eligible patients tested for HER2; test methods used; concordance of test results
      between community and central/reference laboratories; use of trastuzumab by HER2
      test result; and cost effectiveness of testing strategies. RESULTS: Little
      evidence was available to determine whether all eligible patients are tested, how
      many are retested to confirm results, and how many with negative HER2 test
      results still receive trastuzumab. Studies suggested that up to 66% of eligible
      patients had no documentation of testing in claims records, up to 20% of patients
      receiving trastuzumab were not tested or had no documentation of a positive test,
      and 20% of HER2 results may be incorrect. Few cost-effectiveness analyses of
      trastuzumab explicitly considered the economic implications of various testing
      strategies. CONCLUSIONS: There was little information about the actual use of
      HER2 testing in clinical practice, but evidence suggested important variations in
      testing practices and key gaps in knowledge exist. Given the increasing use of
      targeted therapies, it is critical to build an evidence base that supports
      informed decision making on emerging testing technologies in cancer care.

PMID- 19753619
TI  - Quality of life in postoperative vestibular schwannoma patients.
AB  - OBJECTIVES/HYPOTHESIS: To quantify the postoperative quality of life (QOL) in
      patients following vestibular schwannoma surgery in a new multidisciplinary skull
      base unit. STUDY DESIGN: Cross-sectional study. METHODS: The Australian Short
      Form 36 (SF-36) quality of life health questionnaire was administered to 121
      consecutive patients surgically treated for vestibular schwannoma between 1999
      and 2007 at Westmead Hospital, New South Wales, Australia. QOL scores were
      calculated using a standardized process across the eight SF-36 health domains and
      compared to sex- and age- matched healthy Australian population. RESULTS: An 81%
      response rate (98 patients) was obtained. The postoperative QOL in vestibular
      schwannoma patients was significantly less than the appropriate matched healthy
      Australian population in one health domain of role physical limitation (P < .05).
      Analysis of preoperative patient factors (age, gender) and surgical factors such
      as tumor size (cutoff points of 15 mm or 25 mm) together with, surgical approach
      (translabyrinthine and retrosigmoid) showed no significant difference in QOL
      outcomes for each of these variables (P < .05). CONCLUSIONS: Results indicate
      that patients following vestibular schwannoma surgery reported near equivalent
      QOL as the healthy population. Advances in surgical techniques and experiences
      have minimized morbidities associated with vestibular schwannoma surgery.
      Significant physical role limitation encountered postoperatively may relate to
      facial nerve dysfunction, vestibular dysfunction, tinnitus or hearing loss that
      may persist after surgery. Careful patient selection, as well as, appropriate
      preoperative counselling, multidisciplinary follow-up and rehabilitation should
      be offered to all surgical candidates. A measured approach should still be
      considered for patients with small, slow growing tumors with minimal symptoms.

PMID- 19753620
TI  - Retronasal olfactory function in Parkinson's disease.
AB  - OBJECTIVES/HYPOTHESIS: Orthonasal olfaction is severely altered in PD patients.
      Retronasal olfactory function has been shown to be preserved under certain
      conditions even in the absence of orthonasal function. This study was undertaken
      to investigate retronasal versus orthonasal olfactory function in Parkinson's
      disease (PD). STUDY DESIGN: Prospective study. METHODS: A total of 45 PD patients
      (mean age, 61 years; range 26-82 years) underwent orthonasal olfactory testing
      with a standardized olfactory test (Sniffin' Sticks) and retronasal olfactory
      testing with a 10-item identification kit based on aromatized powders. RESULTS:
      Regarding orthonasal tests, all PD patients scored within the range of hyposmia
      and functional anosmia. The mean correct orthonasal identification score for PD
      patients was 56% +/- 2.6%, and the mean retronasal identification rate was 60% +/
      3%. There was no significant difference between ortho- and retronasal odor
      identification (P = .15). CONCLUSIONS: The present study shows that retronasal
      and orthonasal olfactory function are severely impaired in PD patients, and this
      impairment is of similar magnitude for both functions. The contribution of this
      finding to the food-intake behavior of PD patients is discussed.

PMID- 19753621
TI  - A mechanistic study of in vitro degradation of magnesium alloy using
      electrochemical techniques.
AB  - To understand the in vitro degradation mechanism of magnesium alloy,
      electrochemical experiments viz., electrochemical impedance spectroscopy and
      potentiodynamic polarization, were carried out on AZ91 magnesium alloy under
      different experimental conditions. The study suggests: (i) the body temperature
      decreases significantly the corrosion resistance of the alloy, (ii) alkali
      treatment of the alloy enhances the corrosion resistance, and (iii) although
      chloride in simulated body fluid minimizes the corrosion resistance, the presence
      of other constituents viz., phosphate, calcium, and carbonate, enhances the film
      forming tendency and hence increases the corrosion resistance of the alloy.

PMID- 19753622
TI  - Corneal epithelial cell adhesion and growth on EGF-modified aminated PDMS.
AB  - Growth factor tethering has significant potential to mediate cellular responses
      in biomaterials and tissue engineering. We have previously demonstrated that
      epidermal growth factor (EGF) can be tethered to polydimethylsiloxane (PDMS)
      substrates and that these surfaces promoted interactions with human corneal
      epithelial cells in vitro. The goal of the current work was to better understand
      the specific effects of the tethered growth factor on the cells. The EGF was
      reacted with a homobifunctional N-hydroxysuccinimide (NHS) polyethylene glycol
      (PEG) derivative, and then bound to allyamine plasma-modified PDMS. Human corneal
      epithelial cells were seeded on the surfaces and cultured in serum-free medium
      for periods of up to 5 days. Cell growth was monitored and quantified by
      trypsinization and counting with a Coulter counter. Expression of matrix proteins
      and alpha(6)-integrins was assessed by immunostaining and confocal microscopy. A
      centrifugation assay was used to determine cell adhesion under an applied
      detachment force. Binding of EGF was found to significantly increase cell numbers
      and coverage across the surfaces at 5 days of culture in vitro.
      Immunofluorescence experiments indicate increased expression of fibronectin,
      laminin, and alpha(6)-integrins on the EGF-modified surfaces, and expression is
      localized at the cell-material interface as observed by confocal microscopy. In
      accordance with these results, the highest quantity of adherent cells is found on
      the EGF-modified subtrates at 5 days of culture. The results provide initial
      evidence that binding of EGF may be used to improve the epithelialization of and
      the adhesion of the cells on a polymeric artificial cornea device.

PMID- 19753623
TI  - Scale-dependent fiber kinematics of elastomeric electrospun scaffolds for soft
      tissue engineering.
AB  - Electrospun poly(ester urethane)urea (PEUU) scaffolds contain complex multiscale
      hierarchical structures that work simultaneously to produce unique macrolevel
      mechanical behaviors. In this study, we focused on quantifying key multiscale
      scaffold structural features to elucidate the mechanisms by which these scaffolds
      function to emulate native tissue tensile behavior. Fiber alignment was modulated
      via increasing rotational velocity of the collecting mandrel, and the resultant
      specimens were imaged using SEM under controlled biaxial strain. From the SEM
      images, fiber splay, tortuosity, and diameter were quantified in the unstrained
      and deformed configurations. Results indicated that not only fiber alignment
      increased with mandrel velocity but also, paradoxically, tortuosity increased
      concurrently with mandrel velocity and was highly correlated with fiber
      orientation. At microlevel scales (1-10 mum), local scaffold deformation behavior
      was observed to be highly heterogeneous, while increasing the scale resulted in
      an increasingly homogenous strain field. From our comprehensive measurements, we
      determined that the transition scale from heterogenous to homogeneous-like
      behavior to be approximately 1 mm. Moreover, while electrospun PEUU scaffolds
      exhibit complex deformations at the microscale, the larger scale structural
      features of the fibrous network allow them to behave as long-fiber composites
      that deform in an affine-like manner. This study underscores the importance of
      understanding the structure-function relationships in elastomeric fibrous
      scaffolds, and in particular allowed us to link microscale deformations with
      mechanisms that allow them to successfully simulate soft tissue mechanical
      behavior.

PMID- 19753624
TI  - Electroactivity and biocompatibility of polypyrrole-hyaluronic acid multi-walled
      carbon nanotube composite.
AB  - Electroactivity of polypyrrole hyaluronic acid, electropolymerized in the
      presence of oxidized carbon nanotubes (PPyHA-CNT) was studied in situ by
      electrochemical atomic force microscopy (EC-AFM) in physiological electrolyte
      solution. In situ Raman spectroscopic and quartz crystal microbalance (QCM)
      studies were conducted on layers of the polymer grown on AT-cut 5 MHz quartz
      crystals. Human adipose stem cell (ASC) attachment and viability were studied by
      Live/Dead staining, and the proliferation was evaluated by WST-1 Cell
      proliferation assay for polypyrrole samples electropolymerized on titanium.
      According to cyclic voltammetry, the measured specific capacitance of the
      material on gold is roughly 20% of the reference polypyrrole dodecylbenzene
      sulfonate (PPyDBS). Electrochemical-QCM (EC-QCM) analysis of a 210-nm thick film
      reveals that the material is very soft G' approximately 100 kPa and swells upon
      reduction. EC-AFM of samples polymerized on microelectrodes show that there are
      areas of varying electroactivity, especially for samples without a hydrophopic
      backing PPyDBS layer. AFM line scans show typically 20-25% thickness change
      during electrochemical reduction. Raman spectroscopic analysis suggests that the
      material supports noticeable polaron conduction. Biocompatibility study of the
      PPyHA-CNT on titanium with adipose stem cells showed equal or better cell
      attachment, viability, and proliferation compared with the reference polylactide.

PMID- 19753625
TI  - Utilization of micelles formed from poly(ethylene glycol)-block-poly(epsilon
      caprolactone) block copolymers as nanocarriers to enable hydrophobic red two
      photon absorbing emitters for cells imaging.
AB  - A hydrophobic two-photon absorbing (2PA) red emitter (R) was successfully
      incorporated into micelles formed from two block copolymers, poly(epsilon
      caprolactone)-block-poly(ethylene glycol)s, for imaging and toxicity studies. In
      micelles, the chromophore R exhibits a 2PA cross-section of 400 GM (1 GM = 1 x
      10(-50) cm(4) s photon(-1) molecule(-1)) at 820 nm, which is among the highest
      values reported for red 2PA emitters. The micelles with a cationic amino moiety
      containing poly(ethylene glycol) corona showed an enhancement of cell
      internalization and delivered the dye into the cytoplasmic regions of the mouse
      macrophage RAW 264.7 cells. In comparison, the dye in micelles with neutral
      poly(ethylene glycol) as corona could not be delivered into the cells.
      Cytotoxicity of the micelle-R constructs was studied using a 3-(4,5-dimethyl
      thiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. More than 90% of the cells
      were viable after they were stained with the dye-containing micelles at different
      concentrations (dye concentrations of 2-6 muM and polymer concentrations of 0.05
      0.15 mg/mL) for 16 h. This is the first reported application of a hydrophobic
      2,1,3-benzothiadiazole-containing 2PA red emitter delivered into the cytoplasm of
      cells for bioimaging and toxicity assessment.

PMID- 19753626
TI  - Functional groups affect physical and biological properties of dextran-based
      hydrogels.
AB  - Modification of dextran backbone allows the development of a hydrogel with
      specific characteristics. To enhance their functionality for tissue-engineered
      scaffolds, a series of dextran-based macromers was synthesized by incorporating
      various functional groups, including allyl isocyanate (Dex-AI), ethylamine (Dex
      AE), chloroacetic acid (Dex-AC), or maleic-anhydride (Dex-AM) into dextrans. The
      dextran-based biodegradable hybrid hydrogels are developed by integrating
      polyethylene glycol diacrylate (PEGDA). To explore the effect of different
      derivatives on hydrogel properties, three different ratios of Dex/PEGDA are
      examined: low (20/80), medium (40/60), and high (60/40). Differences in physical
      and biological properties of the hydrogels are found, including swelling,
      degradation rate, mechanics, crosslinking density, biocompatibility (in vitro and
      in vivo), and vascular endothelial growth factor release. The results also
      indicate that the incorporation of amine groups into dextran gives rise to
      hydrogels with better biocompatible and release properties. We, therefore,
      conclude that the incorporation of different functional groups affects the
      fundamental properties of a dextran-based hydrogel network, and that amine groups
      are preferred to generate hydrogels for biomedical use.

PMID- 19753627
TI  - Near-peer teaching in anatomy: an approach for deeper learning.
AB  - Peer teaching has been recognized as a valuable and effective approach for
      learning and has been incorporated into medical, dental, and healthcare courses
      using a variety of approaches. The success of peer teaching is thought to be
      related to the ability of peer tutors and tutees to communicate more effectively,
      thereby improving the learning environment. Near-peer teaching involves more
      experienced students acting as tutors who are ideally placed to pass on their
      knowledge and experience. The advantage of using near-peer teachers is the
      opportunity for the teacher to reinforce and expand their own learning and
      develop essential teaching skills. This study describes the design and
      implementation of a program for fourth year medical students to teach anatomy to
      first- and second-year medical students and evaluates the perceptions of the near
      peer teachers on the usefulness of the program, particularly in relation to their
      own learning. Feedback from participants suggests that the program fulfills its
      aims of providing an effective environment for developing deeper learning in
      anatomy through teaching. Participants recognize that the program also equips
      them with more advanced teaching skills that will be required as they move nearer
      toward taking on supervisory and teaching duties. The program has also provided
      the school with an additional valuable and appropriate resource for teaching
      anatomy to first- and second-year students, who themselves view the inclusion of
      near-peer teachers as a positive element in their learning.

PMID- 19753628
TI  - Hyperpolarization of the plasma membrane potential provokes reorganization of the
      actin cytoskeleton and increases the stability of adherens junctions in bovine
      corneal endothelial cells in culture.
AB  - In previous works we showed that the depolarization of the plasma membrane
      potential (PMP) determines a reorganization of the cytoskeleton of diverse
      epithelia in culture, consisting mainly of a reallocation of peripheral actin
      toward the cell center, ultimately provoking intercellular disruption. In view of
      this evidence, we explored in this study the possible effects of membrane
      potential hyperpolarization on the cytoskeletal organization and adherens
      junction (AJ) morphology and the stability of confluent bovine corneal
      endothelial cells in culture. For this purpose, hyperpolarization was achieved by
      substitution of extracellular sodium by nondiffusible cations or via the
      incorporation of valinomycin to the control solution. Actin compactness at the
      cell periphery was assessed by quantitative analysis of fluorescence microscopy
      images. The stability of the AJ was challenged by calcium deprivation or
      temperature decrease. Our results showed that plasma membrane hyperpolarization
      provokes a compaction of AJ-associated actin filaments toward the plasma membrane
      and an increase in the stability of the AJs. We also observed that the
      hyperpolarizing procedures determined similar modifications in the actin
      cytoskeleton of endothelial cells in whole bovine corneas. Together with our
      previous work, the results of this study contribute to the idea that
      modifications in the PMP of nonexcitable cells participate in cellular adaptive
      responses involving reorganization of cytoskeletal components.

PMID- 19753629
TI  - Virtual-core flow cytometry.
AB  - Traditional flow cytometers use a sheath fluid to position particles or cells for
      cytometric measurements, but the need for sheath fluid greatly complicates flow
      cytometric instrumentation. A cytometric detector that is free of the
      requirements of sheath fluid can simplify the design of flow cytometers and can
      extend their use into a number of areas. We designed a flow cytometer that uses a
      combination of three photodetectors to sense the position of a particle in sample
      stream. The position-sensitive detectors create a virtual core in the sample
      stream that eliminates the need for sheath fluid. In this article, we demonstrate
      the efficacy of a virtual-core flow cytometer (VCFC) using test particles,
      immunofluorescently labeled thymocytes, and raw seawater. The VCFC performs
      accurate measurements that can be used for a number of uses including
      environmental monitoring or simple immunology tests.

PMID- 19753630
TI  - Efficient framework for automated classification of subcellular patterns in
      budding yeast.
AB  - Fluorescent-tagging and digital imaging are widely used to determine the
      subcellular location of proteins. An extensive publicly available collection of
      images for most proteins expressed in the yeast S. cerevisae has provided both an
      important source of information on protein location but also a testbed for
      methods designed to automate the assignment of locations to unknown proteins. The
      first system for automated classification of subcellular patterns in these yeast
      images utilized a computationally expensive method for segmentation of images
      into individual cells and achieved an overall accuracy of 81%. The goal of the
      present study was to improve on both the computational efficiency and accuracy of
      this task. Numerical features derived from applying Gabor filters to small image
      patches were implemented so that patterns could be classified without
      segmentation into single cells. When tested on 20 classes of images visually
      classified as showing a single subcellular pattern, an overall accuracy of 87.8%
      was achieved, with 2330 images out of 2655 images in the UCSF dataset being
      correctly classified. On the 4 largest classes of these images, 95.3% accuracy
      was achieved. The improvement over the previous approach is not only in
      classification accuracy but also in computational efficiency, with the new
      approach taking about 1 h on a desktop computer to complete all steps required to
      perform a 6-fold cross validation on all images.

PMID- 19753632
TI  - Mechanics and dynamics of the cytoskeleton: a special issue stemming from the
      2008 ECF Meeting/FEBS Workshop (Mechanics and Dynamics of the Cytoskeleton) in
      Potsdam, Germany.
AB  - Note that Part II of this special issue will appear in the following issue:
      Volume 66, Issue 11, 2009.

PMID- 19753631
TI  - Differentiation of alloreactive versus CD3/CD28 stimulated T-lymphocytes using
      Raman spectroscopy: a greater specificity for noninvasive acute renal allograft
      rejection detection.
AB  - Acute rejection (AR) remains problematic in renal transplantation. As a marker,
      serum creatinine is limited, warranting a more effective screening tool. Raman
      spectroscopy (RS) can detect T-cell activation with high sensitivity. In this
      study we explore its specificity. Seventy-five inactivated, 40 alloantigen
      activated, and 75 CD3/CD28-activated T cells were analyzed using RS. CD3/CD28
      activated peak magnitudes (PM) were 4.3% to 23.9% lower than inactivated PM at
      positions: 903, 1031, 1069, 1093, 1155, 1326, and 1449 cm(-1), with a difference
      in peak ratio (PR) observed at the 1182:1195 cm(-1) position (0.91 +/- 0.06 vs.
      1.2 +/- 0.01, respectively: P = 0.006). Differences in CD3/CD28- and alloantigen
      activated PM were observed at: 903, 1031, 1093, 1155, 1326, and 1449 cm(-1), with
      no PR differences at the 1182:1195 cm(-1) position (0.91 +/- 0.06 vs. 0.86 +/-
      0.09: P = 0.8). Spectral signature separation of CD3/CD28-and alloantigen
      activated groups was 100% specific and sensitive. We conclude that RS can
      differentiate T cells activated by different stimuli with high sensitivity and
      specificity.

PMID- 19753633
TI  - Hemodynamic and intravascular ultrasound assessment of myocardial bridging:
      fractional flow reserve paradox with dobutamine versus adenosine.
AB  - Compared to coronary angiography, both intravascular ultrasound (IVUS) and CT
      angiography provide important information with respect to the morphological
      aspects of myocardial bridging (MB). However, these modalities are limited in
      defining the hemodynamic and clinical significance of MB. Intracoronary Doppler
      studies demonstrate a peculiar abnormal Doppler flow profile associated with MB.
      Fractional flow reserve (FFR) after adenosine infusion has been used to assess
      the hemodynamic significance of MB, but FFR after adenosine induced hyperemia
      underestimates the significance of MB. On the other hand, high-dose dobutamine by
      increasing the contractility of the bridging segment unmasks ischemia induced by
      MB. This review outlines the role of flow velocity measurement by intracoronary
      Doppler, FFR, and IVUS for assessment of patients with MB. In addition, we
      compared FFR measurements after adenosine versus dobutamine infusions for the
      hemodynamic assessment of MB in two patients.

PMID- 19753634
TI  - Transradial simultaneous kissing stenting (SKS) with SheathLess access.
AB  - Transradial coronary intervention is usually performed via a 5 or 6 Fr sheath due
      to the small calibre of radial arteries. Simultaneous kissing stenting (SKS)
      technique requires a guiding catheter 7 Fr or larger and is therefore difficult
      to perform via transradial approach. Conversion to femoral approach or additional
      arterial access is usually required to achieve this goal. To overcome this
      limitation, a hydrophilic 7.5 Fr SheathLess guiding catheter can be exploited.
      This catheter possesses approximately the same size outer diameter as a 6 Fr
      sheath and an internal diameter of a 7.5 Fr catheter. A smooth and successful
      performance of SKS through transradial approach is described using this catheter.

PMID- 19753635
TI  - Long term efficacy of abciximab bolus-only compared to abciximab bolus and
      infusion after transradial coronary stenting.
AB  - BACKGROUND: No data are available on the long term efficacy of abciximab bolus
      only with aspirin and clopidogrel pretreatment and systematic coronary stenting.
      Our objective was to evaluate the 3-year clinical outcomes in the EASY trial.
      METHODS: After a bolus of abciximab (0.25 mg/kg) and uncomplicated transradial
      coronary stenting, 1,005 patients were randomized either to same-day home
      discharge and no infusion (bolus-only group, n = 504) or to overnight
      hospitalization and 12 hours abciximab infusion (bolus + infusion group, n =
      501). In contrast, 343 patients were not randomized after stenting for safety
      reasons and received abciximab bolus and infusion (not-randomized group). The
      rate of major adverse cardiovascular events (MACE), including death, myocardial
      infarction (MI) and target vessel revascularization (TVR) after percutaneous
      coronary intervention (PCI) was evaluated. RESULTS: Up to 3 years, the incidence
      of MACE remained similar in the two randomized groups, 14% in bolus-only vs. 17%
      in bolus + infusion (P = 0.38). Similar efficacy was observed in subgroups
      analysis including higher-risk patients such as those with diabetes, unstable
      angina or non-ST elevation MI. Conversely, the incidence of MACE remained
      significantly higher in patients not-randomized post-PCI at all time intervals (P
      < 0.0001). The difference in outcomes between randomized and not-randomized
      patients was mostly accounted by the higher rates of MI, TVR as survival rate
      remained similar. CONCLUSION: In patients pretreated with aspirin and clopidogrel
      and undergoing uncomplicated coronary artery stenting, abciximab bolus-only was
      associated with similar outcomes compared with bolus followed by infusion, up to
      3 years after PCI. Conversely, patients with suboptimal results or clinical
      complications during PCI remained at higher risk of late revascularization or MI.

PMID- 19753636
TI  - Five-year clinical outcomes after coronary stenting of chronic total occlusion
      using sirolimus-eluting stents: insights from the rapamycin-eluting stent
      evaluated at Rotterdam Cardiology Hospital-(Research) Registry.
AB  - BACKGROUND: The use of drug eluting stents (DES) in patients with a successfully
      recanalized chronic total occlusion (CTO) has been associated with a significant
      decrease in the need for repeat revascularization, and a favorable short-term
      clinical outcome when compared with the use of bare metal stents (BMS). Our
      group, however, has previously reported similar rates of target lesion
      revascularisation (TLR) and major adverse cardiovascular events (MACE) at 3 years
      follow-up in patients with a successfully opened CTO who were treated with either
      a sirolimus eluting stent (SES) or a BMS. The objective of this report was to
      evaluate the outcomes of these patients at 5-years clinical follow-up. METHODS
      AND RESULTS: A total of 140 (BMS 64, SES 76) patients with successfully opened
      CTOs were included. Seven patients died in the BMS group whilst nine patients
      died in the SES group (P = 0.90). Noncardiac death was the major component of all
      cause mortality (11 noncardiac deaths vs. 5 cardiac). There were two and three
      myocardial infarctions (MI) in the BMS and SES group, respectively (P = 1.0). The
      composite of death and MI occurred in seven (10.9%) and eleven (14.5%) patients
      in the BMS and SES group, respectively (P = 0.53). Clinically driven TLR was
      performed in eight patients (12.5%) in the BMS group, and five (6.6%) in the SES
      group (P = 0.26). Non-TLR target vessel revascularization was performed in one
      patient in the BMS group, and four in the SES group (P = 0.37). The 5-year device
      oriented cumulative MACE rate was 15.6% and 11.8% in the BMS and SES group,
      respectively (P = 0.56). CONCLUSION: In patients with a successfully treated CTO,
      clinical outcome after 5 years was similar between SES and BMS, however,
      clinically driven TLR was slightly higher in the BMS group.

PMID- 19753637
TI  - Diagnostic accuracy of 64 multidetector computed tomographic angiography in
      peripheral vascular disease.
AB  - BACKGROUND: Previous studies of multidetector CT (MDCT) of the lower extremities
      for the detection of peripheral vascular disease showed high diagnostic accuracy
      but were performed with older generation systems. OBJECTIVE: The purpose of this
      study was to evaluate the diagnostic accuracy of 64 MDCT for the detection of
      hemodynamically significant disease within the lower extremity peripheral
      vasculature as compared to digital subtraction angiography (DSA). METHODS: Twenty
      eight consecutive patients with symptomatic lower extremity intermittent
      claudication and an abnormal ankle-brachial index (ABI; less than 0.9) were
      evaluated by both 64 MDCT and DSA. Axial images were acquired with a 64
      multidetector general electric light speed VCT scanner. Images were analyzed
      using a GE Advantage workstation (AW 4.3) capable of advanced image processing
      and manipulation. The aorto-iliac and lower extremity arteries were divided into
      15 segments per limb (30 segments per patient). Eight hundred forty segments were
      analyzed in a blinded fashion by physicians with level III CT certification.
      Segments were classified as grade I (<10% stenosis), grade II (10-49%), grade III
      (50-99%), and grade IV (occlusion). RESULTS: For all segments evaluated, the
      overall diagnostic accuracy for detecting grade III and IV lesions was 98% with a
      sensitivity of 99% and a specificity of 98%. For the aorto-iliac segments, the
      diagnostic accuracy was 98% with a sensitivity of 100% and a specificity of 99%.
      For the femoro-popliteal segments, the overall accuracy was 98% with a
      sensitivity of 100% and a specificity of 99%. For the infra-popliteal segments,
      the overall accuracy was 98% with a sensitivity of 97% and a specificity of 99%.
      One segment could not be visualized by MDCT compared to 49 segments that could
      not be visualized by DSA. CONCLUSIONS: This study demonstrates excellent
      diagnostic accuracy of 64 MDCT in the detection of hemodynamically significant
      disease of the lower extremities. More segments are visualized using 64 MDCT than
      DSA, allowing more complete visualization of the vascular tree. CT angiography
      should be considered in the diagnostic evaluation of symptomatic patients with
      peripheral vascular disease.

PMID- 19753638
TI  - Human cell toxicogenomic analysis of bromoacetic acid: a regulated drinking water
      disinfection by-product.
AB  - The disinfection of drinking water is a major achievement in protecting the
      public health. However, current disinfection methods also generate disinfection
      by-products (DBPs). Many DBPs are cytotoxic, genotoxic, teratogenic, and
      carcinogenic and represent an important class of environmentally hazardous
      chemicals that may carry long-term human health implications. The objective of
      this research was to integrate in vitro toxicology with focused toxicogenomic
      analysis of the regulated DBP, bromoacetic acid (BAA) and to evaluate modulation
      of gene expression involved in DNA damage/repair and toxic responses, with
      nontransformed human cells. We generated transcriptome profiles for 168 genes
      with 30 min and 4 hr exposure times that did not induce acute cytotoxicity. Using
      qRT-PCR gene arrays, the levels of 25 transcripts were modulated to a
      statistically significant degree in response to a 30 min treatment with BAA (16
      transcripts upregulated and nine downregulated). The largest changes were
      observed for RAD9A and BRCA1. The majority of the altered transcript profiles are
      genes involved in DNA repair, especially the repair of double strand DNA breaks,
      and in cell cycle regulation. With 4 hr of treatment the expression of 28 genes
      was modulated (12 upregulated and 16 downregulated); the largest fold changes
      were in HMOX1 and FMO1. This work represents the first nontransformed human cell
      toxicogenomic study with a regulated drinking water disinfection by-product.
      These data implicate double strand DNA breaks as a feature of BAA exposure.
      Future toxicogenomic studies of DBPs will further strengthen our limited
      knowledge in this growing area of drinking water research.

PMID- 19753639
TI  - Lessons from geographic mapping of IBD in France.

PMID- 19753640
TI  - Optimizing prevention of hospital-acquired venous thromboembolism (VTE):
      prospective validation of a VTE risk assessment model.
AB  - BACKGROUND: Hospital-acquired (HA) venous thromboembolism (VTE) is a common
      source of morbidity/mortality. Prophylactic measures are underutilized. Available
      risk assessment models/protocols are not prospectively validated. OBJECTIVES:
      Improve VTE prophylaxis, reduce HA VTE, and prospectively validate a VTE risk
      assessment model. DESIGN: Observational design. SETTING: Academic medical center.
      PATIENTS: Adult inpatients on medical/surgical services. INTERVENTIONS: A simple
      VTE risk assessment linked to a menu of preferred VTE prophylaxis methods,
      embedded in order sets. Education, audit/feedback, and concurrent identification
      of nonadherence. MEASUREMENTS: Randomly sampled inpatient audits determined the
      percent of patients with "adequate" VTE prevention. HA VTE cases were identified
      concurrently via digital imaging system. Interobserver agreement for VTE risk
      level and judgment of adequate prophylaxis were calculated from 150 random
      audits. RESULTS: Interobserver agreement with 5 observers was high (kappa score
      for VTE risk level = 0.81, and for judgment of "adequate" prophylaxis = 0.90).
      The percent of patients on adequate prophylaxis improved each of the 3 years
      (58%, 78%, and 93%; P < 0.001) and reached 98% in the last 6 months of 2007; 361
      cases of HA VTE occurred over 3 years. Significant reductions for the risk of HA
      VTE (risk ratio [RR] = 0.69; 95% confidence interval [CI] = 0.47-0.79) and
      preventable HA VTE (RR = 0.14; 95% CI = 0.06-0.31) occurred. We detected no
      increase in heparin-induced thrombocytopenia (HIT) or prophylaxis-related
      bleeding using administrative data/chart review. CONCLUSIONS: We prospectively
      validated a VTE risk-assessment/prevention protocol by demonstrating ease of use,
      good interobserver agreement, and effectiveness. Improved VTE prophylaxis
      resulted in a substantial reduction in HA VTE.

PMID- 19753641
TI  - Response to "Hermann Stieve's clinical-anatomical research on executed women
      during the 'Third Reich'".

PMID- 19753642
TI  - Comment on "Inguinal canal development: the muscular wall and the role of the
      gubernaculum".

PMID- 19753643
TI  - Prevalence of previously unknown elevation of glycosylated hemoglobin in spine
      surgery patients and impact on length of stay and total cost.
AB  - BACKGROUND: Elevated levels of glycosylated hemoglobin (HbA1c) among spine
      surgery patients may have an impact on length of stay (LOS) and healthcare cost.
      MATERIALS AND METHODS: We retrospectively reviewed the charts of 556 spine
      surgery patients who underwent 1 of 3 types of surgery: lumbar microdiscectomy
      (LMD), anterior cervical decompression and fusion (ACDF), and lumbar
      decompression and fusion (LDF). Information was collected about their diabetes
      mellitus (DM) history and HbA1c levels. We used HbA1c 6.1% as the screening
      cutpoint. Percentages of nondiabetic patients, those with subclinical elevation
      of HbA1c and those with already known DM were calculated and statistical analysis
      was applied. RESULTS: After excluding the small group of well-controlled DM (n =
      14), 72.4% of patients were nondiabetic, 14.3% were subclinical patients with
      previously unknown HbA1c elevation, and 13.3% were already known, confirmed DM
      patients. There were significant differences in the LDF group between the "No DM"
      and "Subclinical" groups (P < 0.05) in terms of cost and LOS (P < 0.05). Age and
      body mass index (BMI) were very significant predictors of total cost in spine
      surgery patients (P <or= 0.001), in addition to the type of surgery. Univariate
      analysis with age, BMI, or both as covariates deprived DM-HbA1c status of
      statistical significance (P > 0.05) in determining cost. CONCLUSIONS: There is a
      significant segment of spine surgery patients who were unaware of their elevated
      HbA1c status before their preoperative visit. These patients seem to utilize more
      healthcare resources, which is especially evident in the LDF group. We believe
      that HbA1c should be considered in the routine preoperative workup of spine
      surgery patients.

PMID- 19753644
TI  - Perineal groove: A rare congenital abnormality of failure of fusion of the
      perineal raphe and discussion of its embryological origin.
AB  - We present a case where a baby girl was born with failure of fusion of the
      perineal raphe. To our knowledge, there has been limited reports of this form of
      congenital abnormality in the literature and is referred to as "perineal groove."
      The incidence of perineal groove is unclear but it is considered to be rare. This
      case reviews the embryological origin of this congenital abnormality.

PMID- 19753645
TI  - The pattern of the thoracic splanchnic nerves as they pass through the diaphragm.
AB  - The formation and structure of the greater, lesser, and least thoracic splanchnic
      nerves is highly variable in their intrathoracic as well as their
      subdiaphragmatic portion. Splanchnicectomies for pain control of otherwise
      intractable upper abdominal pain and other surgical procedures are dependent on
      the detailed knowledge of the anatomy of these nerves and their variations. Many
      commonly used anatomical illustrations depict the passage of the thoracic
      splanchnic nerves through the diaphragm uniformly as three nerves penetrating the
      crura in three separate locations along a rough superoinferior line. As this
      pattern does not correspond with our own sporadic observations, we performed a
      series of dissections to study the exact anatomy of this area. Dissections of 24
      donors revealed that the most common pattern of diaphragmatic passage of these
      three nerves is through a single location in each crus. From this crural
      passageway, the three nerves then diverge to reach their targets, with the
      greater thoracic splanchnic nerve bending anteriorly at nearly 90 degrees to
      enter the posterolateral edge of the celiac ganglion. Modern anatomical
      illustrations should depict these most common patterns of the subdiaphragmatic
      portion of the thoracic splanchnic nerves and mention the great variability of
      their formation and structure.

PMID- 19753646
TI  - Response to "The beginning of the evidence-based morphology".

PMID- 19753648
TI  - Mobilization effects of G-CSF, GM-CSF, and darbepoetin-alpha for allogeneic
      peripheral blood stem cell transplantation.
AB  - The effects of GM-/G-CSF and darbepoetin-alpha on stem cell mobilization were
      investigated. From February 2005 to March 2007, 30 allogeneic sibling donors were
      randomly assigned to a G-CSF group (5 microg/kg/day for 5-7 days) or triple group
      (GM-CSF 10 microg/kg/day on 1st and 2nd day, G-CSF 5 microg/kg/day for 5-7 days,
      and darbepoetin-alpha 40 mg on 1st day). The MNCs and CD34(+) cells were not
      different between the two groups, although the doses (x10(8)/kg of recipient body
      weight) of CD3(+) cells (3.64 +/- 1.75 vs. 2.63 +/- 1.36, P = 0.089) and CD8(+)
      cells (1.07 +/- 0.53 vs. 0.60 +/- 0.30, P = 0.006) were lower in the triple
      group. The engraftments, frequency of RBC transfusions, and hemoglobin recovery
      were not different between the two groups. The cumulative incidence of overall
      and Grades II-IV aGVHD was 64.3% vs. 61.1% and 25.9% vs. 27.1% in the G-CSF and
      triple regimen group, respectively, whereas the cumulative incidence of cGVHD was
      20.8 +/- 1.3% and 24.4 +/- 1.7%, respectively. In conclusion, the triple regimen
      did not seem to be superior to G-CSF alone in terms of the CD34+ cell dose,
      hemoglobin recovery, and GVHD. However, the CD8+ cell count was significantly
      lower in the triple regimen group. The role of a lower CD8+ cell count in the
      graft may need to be elucidated in the future.

PMID- 19753647
TI  - Developmental craniofacial anthropometry: Assessment of race effects.
AB  - Differences in craniofacial anatomy among racial groups have been documented in a
      variety of structures, but the oral and maxillofacial regions have been shown to
      be a particularly defining region of variability between different racial/ethnic
      groups. Such comparisons are informative, but they neither address developmental
      changes of the craniofacial anatomy nor do they assess or take into account the
      natural variability within individual races that may account for similar
      reported, across-group variations. The purpose of this report was to compare
      using medical imaging studies-the growth trend of select race-sensitive
      craniofacial variables in the oral and pharyngeal regions when all races [White,
      Asian, Black, and Hispanic (AR)] are included versus only a single race category
      [White (WR)]. Race effect was tested by comparing sex-specific growth fits
      (fourth degree polynomial model) for AR versus WR data. Findings indicate that
      the inclusion of all races versus a single race did not significantly alter the
      growth model fits. Thus, the inclusion of all races permits the advancement of
      general growth models; however, methodologically, it is best to treat the race
      variable as a covariate in all future analysis to test for both potential all
      race effects or individual race effects, on general growth models.

PMID- 19753649
TI  - LDL lipid apheresis rapidly increases peripheral endothelial progenitor cell
      competence.
AB  - BACKGROUND AND AIM: Endothelial progenitor cells (EPCs) have been shown to
      promote neovascularization under physiologic and pathologic conditions. Statins
      have been documented to increase the total number of circulating EPCs in long
      term treated patients. Lipid apheresis is used to treat patient with refractory
      hyperlipidemia. The aim of our study was to evaluate whether lipid apheresis is
      associated with EPC mobilization. METHODS: Thirteen patients with refractory
      hyperlipidemia (analysis at the beginning and at the end of a single lipid
      apheresis treatment) and 10 healthy controls were included into the study. For
      quantifying total peripheral EPCs, CD133+/Flk-1+ myelo-monocytic blood cells were
      enumerated by flow cytometry. The proliferative potential of EPCs was evaluated
      by a "colony-forming unit" assay. In some patients, EPC eNOS expression was
      evaluated before and after treatment. RESULTS: Circulating EPCs and the cells'
      proliferative activity were lower in hyperlipidemia patients as compared to
      controls (0.14 +/- 0.07 vs. 0.6 +/- 0.14, P = 0.01, and 13.9 +/- 4.9 vs. 45.6 +/-
      8.1, P = 0.0007). Lipid apheresis treatment was not associated with an increase
      in total EPCs. The cells' proliferative activity was strongly stimulated by lipid
      apheresis as reflected by an increase in the number of EPC colonies (13.9 +/- 4.9
      to 34.1 +/- 7.3, P = 0.035). Analysis of EPC eNOS expression revealed a threefold
      increase in the cellular expression intensity after lipid apheresis. CONCLUSIONS:
      Patients with refractory hyperlipidemia exhibit lower peripheral EPC numbers and
      a lower proliferative activity of circulating EPCs than healthy controls. A
      single lipid apheresis treatment significantly stimulates EPC proliferation, it
      furthermore increases cellular eNOS. In summary, these results show that lipid
      apheresis mediates beneficial effects on the EPC system as an essential element
      in the process of vascular repair in the human organism.

PMID- 19753651
TI  - Histological and ultrastructural characterization of the alimentary system of
      solifuges (Arachnida, Solifugae).
AB  - Solifuges are voracious and fast predators. Once having captured a prey item,
      mostly small arthropods or even small vertebrates, they start feeding on their
      prey by constant chewing movements with their huge chelicerae. At the same time,
      they squeeze out the soft tissue that passes the anterior lattice-like part of
      the mouthparts. The digestion of the food takes place in the midgut, which is
      anatomically highly complex. It consists of the midgut tube from which numerous
      prosomal and opisthosomal diverticula and tubular lateral branches arise. The
      dimorphic epithelium of the midgut tube and the diverticula is constituted of
      digestive and secretory cells. The digestive cells are characterized by an apical
      tubulus system and contain nutritional vacuoles, lipids, spherites, and glycogen.
      Secretory cells contain a huge amount of rough endoplasmic reticulum and
      secretory vacuoles. The lateral branches are ultrastructurally similar to
      Malpighian tubules and are likely involved in excretion. In contrast to the
      midgut, the epithelium of the hindgut consists of only one type of cell overlain
      by a thin cuticle. Digested residuals are stored in the hindgut until defecation.

PMID- 19753652
TI  - Coenzyme Q10 protects against oxidative stress-induced cell death and enhances
      the synthesis of basement membrane components in dermal and epidermal cells.
AB  - Coenzyme Q10 (CoQ10), which has both energizing and anti-oxidative effects, is
      also reported to have antiaging action, e.g., reducing the area of facial
      wrinkles. However, the mechanism of its anti-aging activity is not fully
      established. Here, we examined the effect of CoQ10 on human dermal and epidermal
      cells. CoQ10 promoted proliferation of fibroblasts but not keratinocytes. It also
      accelerated production of basement membrane components, i.e., laminin 332 and
      type IV and VII collagens, in keratinocytes and fibroblasts, respectively;
      however, it had no effect on type I collagen production in fibroblasts. CoQ10
      also showed protective effects against cell death induced by several reactive
      oxygen species in keratinocytes, but only when its cellular absorption was
      enhanced by pretreatment of the cells with highly CoQ10-loaded serum. These
      results suggest that protection of epidermis against oxidative stress and
      enhancement of production of epidermal basement membrane components may be
      involved in the antiaging properties of CoQ10 in skin.

PMID- 19753653
TI  - Dehydroabietic acid, a diterpene, improves diabetes and hyperlipidemia in obese
      diabetic KK-Ay mice.
AB  - Terpenoids, which are contained in a large number of dietary and herbal plants,
      have many biological effects. In this study, the effects of dehydroabietic acid
      (DAA), a diterpene, on glucose and lipid metabolism were examined using obese
      diabetic KK-Ay mice. We showed here that DAA treatment decreased not only plasma
      glucose and insulin levels but also plasma triglyceride (TG) and hepatic TG
      levels. To examine the mechanism underlying the effects of DAA, the production of
      inflammatory cytokines was measured. It was shown that the DAA treatment
      suppressed the production of monocyte chemoattractant protein-1 (MCP-1) and tumor
      necrosis factor-alpha (TNFalpha) (proinflammatory cytokines) and increased that
      of adiponectin (an anti-inflammatory cytokine). As a result of the changes in the
      production of inflammatory cytokines caused by the DAA treatment, the
      accumulation of macrophages in adipose tissues was reduced. These results
      indicate that treatment with DAA improves the levels of plasma glucose, plasma
      insulin, plasma TG, and hepatic TG through the decrease in the macrophage
      infiltration into adipose tissues, suggesting that DAA is a useful food-derived
      compound for treating obesity-related diseases.

PMID- 19753654
TI  - Granulocyte transfusion therapy in abdominal organ transplant recipients.
AB  - BACKGROUND: Patients with neutropenia are at increased risk for infections.
      Granulocyte transfusions (GT) have had mixed success in treatment of neutropenic
      infections in adult patients with hematologic malignancy. This study examined the
      outcomes of GT therapy in neutropenic solid organ transplant recipients, a novel
      population for this therapy. METHODS: We performed a retrospective examination of
      the transfusion and medical records of all 14 solid organ-transplant recipients
      without hematologic malignancy who experienced neutropenia and received GT
      therapy from 2004 to 2006. RESULTS: Twelve patients received GT therapy for an
      active infection and two patients for infection prophylaxis. The mean absolute
      neutrophil count (ANC) one day increment per GT in these patients was 526/microl
      (median 215/microl). The mean ANC one day increment per dose of 10(10)
      granulocytes was 246/microl (median 86/microl). Of the 12 infected patients, four
      patients (33%) showed a clinical response to GT with improvement or resolution of
      the infection, 7 (58%) patients had no clinical response and one additional
      patient had a clinical response to a course of GT but died during a second GT
      course. Neither patient receiving GT for prophylaxis developed an infection.
      CONCLUSIONS: We observed temporal increases in ANC to levels above 1,000/microl
      in 15/18 (83.3%) courses of GT. We observed a clinical response to infection in
      5/12 (42%) patients, the remaining infected patients had no clinical response.
      Our results suggest that GT therapy in neutropenic solid organ transplant
      recipients can boost peripheral blood neutrophil counts. Additional studies are
      needed to document an independent clinical benefit for GT in this patient
      population.

PMID- 19753655
TI  - Left ventricular cardiac function in fetuses with congenital diaphragmatic hernia
      and the effect of fetal endoscopic tracheal occlusion.
AB  - OBJECTIVES: The pre-existing compression of the left ventricle in congenital
      diaphragmatic hernia (CDH) could be aggravated by the amplified lung growth after
      fetoscopic endoluminal tracheal occlusion (FETO). Our aim was to document left
      ventricular (LV) size and function in fetuses with isolated left-sided CDH and to
      document the effect of FETO on the fetal heart. METHODS: We determined cardiac
      axis, LV diameters, ejection fraction, shortening fraction, mitral E/A index and
      myocardial performance index (MPI) in 27 fetuses with isolated left-sided CDH,
      and compared these with values in a reference population (n = 117). In fetuses
      with severe CDH that subsequently underwent FETO and/or reversal of occlusion,
      additional measurements were obtained 24 h before and after each fetal
      intervention. We recorded fetal electrocardiograms non-invasively in six CDH
      fetuses and compared the duration of the QRS complex with data obtained from 12
      controls. RESULTS: LV end-diastolic diameter was 32% smaller in CDH fetuses than
      in controls (P < 0.0001) but LV function was comparable. QRS duration was no
      different between CDH and control fetuses. FETO did not affect cardiac size but
      reduced the MPI (P = 0.004). Reversal of FETO had no significant effect on
      cardiac size and function. CONCLUSIONS: CDH fetuses have a smaller left ventricle
      than do healthy fetuses. There is no overall adverse impact of CDH and FETO on LV
      cardiac function.

PMID- 19753656
TI  - Gestational sac volume: comparison between SonoAVC and VOCAL measurements at 11 +
      0 to 13 + 6 weeks of gestation.
AB  - OBJECTIVES: To assess the novel three-dimensional (3D) tool, Sonography-based
      Automated Volume Count (SonoAVC) in the calculation of gestational sac volume at
      11 + 0 to 13 + 6 weeks of gestation, to correlate the measurements with those
      obtained using Virtual Organ Computed-aided AnaLysis (VOCAL) and to study the
      reproducibility of SonoAVC volume calculation of this irregularly shaped
      structure. METHODS: We acquired 3D volumes of the uterus in 65 pregnancies at 11
      + 0 to 13 + 6 weeks of gestation. We performed volume calculation of the
      gestational sac, excluding the fetus and the placenta, using VOCAL with 15
      degrees 12-step rotation. We then repeated the calculation with three different
      SonoAVC settings and compared both techniques. In 30 cases we assessed the
      reproducibility of the SonoAVC volume calculations. RESULTS: In 95% of cases it
      was possible to calculate the gestational sac volume with SonoAVC. This volume
      increased with advancing gestation and the volumes were expressed as delta values
      to compare the measurements made with VOCAL and the three different SonoAVC
      settings. There was no difference between delta values of gestational sac volume
      calculated using VOCAL and SonoAVC with high and medium growth settings.
      Reproducibility analysis showed good results. CONCLUSION: Gestational sac volume
      calculation is feasible with SonoAVC in most cases and does not differ from that
      performed using VOCAL. High and medium growth SonoAVC settings seem to be more
      accurate for gestational sac volume calculation, although larger studies are
      required for standardization of the technique. The reproducibility analysis
      showed similar results to those previously published.

PMID- 19753657
TI  - Proceedings of a meeting to honor Endel Tulving on his 80th birthday. Tallinn,
      Estonia.

PMID- 19753658
TI  - [Proceedings of Visceral Medicine 2009. September 30-October 3, 2009. Hamburg,
      Germany].

PMID- 19753659
TI  - Proceedings of a roundtable on combination therapy for age-related macular
      degeneration. Philadelphia, Pennsylvania, USA.

PMID- 19753660
TI  - Functional genomics towards personalized healthcare. Proceedings of the 4th
      Biologie Perspective Santorini Conference. 2008. Santorini, Greece.

PMID- 19753661
TI  - Diffuse bowel lesions: a possible cause of diffuse abdominal pain.

PMID- 19753662
TI  - Jousting with windmills requires a  dose of tough love.

PMID- 19753663
TI  - An intron 1 polymorphism in the   cholecystokinin-A receptor gene associated  
      with schizophrenia in males.
AB  - OBJECTIVE: To identify whether a genetic variation (rs1800857; IVS1-5T>C) in the
      neuropeptide cholecystokinin-A receptor (CCKAR) gene is a risk factor in the
      pathogenesis of schizophrenia. METHOD: The variation was analysed in a case
      control design comprising 508 patients with schizophrenia and 1619 control
      subjects. A possible functional impact of this variant on CCKAR protein synthesis
      through alterations in splicing was analysed in an exon-trapping assay. RESULTS:
      In males only, the risk variant, IVS1-5C, was associated with a significantly
      increased risk of schizophrenia. Carrying one risk allele was associated with an
      increased risk of 1.74 (Odds Ratio, OR) and homozygosity (CC) was associated with
      an OR of 3.19. The variation had no impact on protein synthesis of CCKAR.
      CONCLUSION: This is the first report associating the CCKAR gene variant with
      schizophrenia specifically in men. Our study strengthens the conclusion that a
      CCKAR dysfunction could be involved in the aetiology of schizophrenia.

PMID- 19753664
TI  - Response to managed care.

PMID- 19753665
TI  - New domain gives medical field source of information.

PMID- 19753666
TI  - ADHA advises on ways to maintain oral health, prevent disease.

PMID- 19753667
TI  - Health dangers encourage periodontists to help smokers.

PMID- 19753668
TI  - Post mastectomy adjuvant radiotherapy in breast cancer: a comparison of three
      hypofractionated protocols.

PMID- 19753669
TI  - "Disagreement: the end of the beginning or the beginning of the end"?

PMID- 19753670
TI  - Oral pathology quiz #63. Case number 3. Least likely odontogenic myxoma.

PMID- 19753671
TI  - Oral pathology quiz #63. Case number 4. Dentigerous cyst.

PMID- 19753672
TI  - Proceedings of the Mouse as an Instrument for Ear Research III Meeting. September
      18-21, 2008. Bar  Harbor, Maine, USA.

PMID- 19753673
TI  - Treating anorexia nervosa.  A multidisciplinary approach is best, but relapses
      are common.

PMID- 19753674
TI  - Heavy heart, thin bones?  The evidence suggests that selective serotonin reuptake
      inhibitors may erode bone.

PMID- 19753675
TI  - Infectious health behaviors.  A theory about how health and emotions may spread.

PMID- 19753676
TI  - Divalproex is not effective for children with bipolar disorder.

PMID- 19753677
TI  - Commentary.  As we were putting together our August issue, and with summer's more
      leisurely pace in view, a recent article extolling the virtues of play and
      relaxation seemed timely.

PMID- 19753678
TI  - Asthma medication - persistence with adrenergics,  steroids and combination
      products over a 5-year period.
AB  - BACKGROUND: Many patients with asthma underuse steroids for inhalation. This has
      been identified as a main cause of therapy failure and of excess health care
      utilization. OBJECTIVE: To elucidate the medication persistence of patients using
      asthma drugs, how patients combine the drugs over time and whether medication
      persistence was influenced by patients switching to combination products.
      METHODS: Individual patients' drug acquisition data were obtained from a pharmacy
      record database for the period 2000-2004. A patient was considered to have
      satisfactory medication possession ratio (MPR) if the medication supplies covered
      >or=80% of the prescribed treatment. Drug use profiles were constructed as graphs
      for each patient, showing the date of each refill and the time period covered by
      the dispensed drugs. From the graphs the combination of drugs, the continuity of
      the therapy over time and the MPR for each patient could be determined. RESULTS:
      Of 1812 patients with asthma drugs in the database, 815 fulfilled the inclusion
      criteria. The percentage of patients with satisfactory MPR was low (11-27%), but
      significantly higher among patients using combination products than among those
      using steroids. For patients who switched from adrenergics plus steroids in two
      inhalers to combination products in one inhaler, the number of patients with
      satisfactory MPR was significantly increased. CONCLUSION: Satisfactory MPR was
      low for all types of asthma drugs. More patients had satisfactory MPR with
      combination products in one inhaler than with adrenergics and steroids in two
      separate inhalers. Asthma drug-delivery is important and combination products of
      the two ingredients could therefore improve asthma therapy.

PMID- 19753679
TI  - Two sampling time profiles for the abbreviated estimation  of mycophenolic acid
      area under the curve in adult  renal transplant recipients treated with
      mycophenolate  mofetil and concomitant tacrolimus.
AB  - OBJECTIVE: Various studies have revealed that mycophenolic acid (MPA) area under
      the time concentration curve (AUC) may have clinical value in mycophenolate
      mofetil dose adjustment. As the full AUC measurement is impractical in clinical
      practice, several abbreviated AUC profiles using pre-dose, and two or three post
      dose samples have been proposed; however, the possible use of lower sampling time
      profiles has an unquestionable practical interest, and the aim of our study was
      the evaluation of several two-points algorithms using only one post-dose sample.
      PATIENTS AND METHODS: In 60 MPA concentration-time profiles from 37 adult renal
      transplant patients treated with mycophenolate mofetil and concomitant
      tacrolimus, the MPA AUC values were estimated using the three sampling time
      algorithm (pre-dose, one-half and 2 h post-dose)of Pawinski et al. (Clinical
      Chemistry 48, 2002, 1497), trapezoidal extrapolated procedure according to Hale
      et al. (Clinical Pharmacology Therapeutics 64, 1998, 672), and two-points
      algorithm (pre-dose and 2 h post-dose) proposed by David-Neto et al. (Clinical
      Transplantation 19, 2005, 19). RESULTS: The AUC values estimated using the
      algorithm of Pawinski et al. had a very high correlation(r = 0.997, P < 0.001)
      with the trapezoidal extrapolated AUC results. The estimated AUC values obtained
      using the two-points algorithm of David-Neto et al. present a high correlation (r
      = 0.930, P < 0.001), acceptable mean prediction error (+3.3 +/- 1.8%), and a
      diagnostic efficiency of 94% in the classification of subtherapeutic,
      therapeutic, and supratherapeutic values, with respect to the three-points
      algorithm of Pawinskiet al. CONCLUSION: The two sampling time algorithm of David
      Neto gave similar results to those of the three-sampling time algorithm of
      Pawinski, and both, with sampling over 2 h, may be useful for routine MPA AUC
      estimation in renal transplant recipients with concomitant tacrolimus. Both are
      unsuitable when unusually unpredictable pharmacokinetics are expected such as
      with entericcoated formulations.

PMID- 19753680
TI  - Drug-use pattern of Chinese herbal medicines in  insomnia: a 4-year survey in
      Taiwan.
AB  - BACKGROUND AND OBJECTIVE: Insomnia is a common complaint in the general
      population. Interest in the use of alternative treatments for insomnia is
      increasing exponentially and is fairly common in Taiwan. We undertook a survey to
      define the drug utilization patterns of Chinese herbal medicines (CM) for
      insomnia in Taiwan. METHODS: The survey was conducted over a period of 4 years,
      from January 2003 to December 2006. Outpatients with primary insomnia and being
      treated with CM were studied. Core drug-use indicators were the number of CM
      items per prescription, the dosing frequency and duration of CM prescriptions,
      the most common prescribed CM herbs and CM formulae used. RESULTS: Six thousand
      eight hundred and sixty patients, using 37,046 CM herb items, were screened
      during the study period. The average CM items per prescription was 5.40. Most of
      prescriptions (95.23%) were prescribed for administration three times a day. The
      most often prescribed Chinese herbal products were Hong-Hwa (Carthamus
      tinctorius) and Jia-Wey-Shiau-Yau-San, which includes Angelica sinensis,
      Atractylodes macrocephala, Paeonia lactiflora, Bupleurum chinense, and Poria
      coco. CONCLUSION: This is the first extensive survey examining the drug
      utilization patterns of Chinese herbal medicines in the treatment of insomnia.
      Although the data were generated in Taiwan, the herbs and practices identified
      are likely to be widely generalizable wherever Chinese herbal remedies are used
      for insomnia. Multiple herbs and complex formulae were commonly used. The
      baseline data generated should be of use in informing subsequent studies,
      including those aimed at a thorough evaluation of the herbs' effectiveness.

PMID- 19753681
TI  - Superficial siderosis of the central nervous  system - treatment with steroids?
AB  - Steroids have been suggested as a therapeutic option for superficial siderosis of
      the central nervous system (SSCNS) without identifiable bleeding source.
      Longitudinal observational data of a patient with idiopathic SSCNS who was
      repeatedly treated with methylprednisolone over a course of 2 years are reported.
      The case history is critically discussed on the background of the sparse
      literature. In conclusion, if at all, there is only a limited and temporary,
      mostly subjective clinical response to steroids in SSCNS. Systematic studies of
      this medication in SSCNS do not seem warranted. Pathophysiological considerations
      hopefully may lead to more helpful medications for this chronic and debilitating
      disorder.

PMID- 19753682
TI  - CYP2C19 genotype-based (R)-warfarin disposition  assessment: some views on data
      analysis.

PMID- 19753683
TI  - [Vaccination campaigns against poliomyelitis in Spain in 1963].
AB  - Two anti-poliomyelitic vaccination campaigns coexisted in 1963: the Salk vaccine
      used by the Compulsory Health Insurance and the pilot experience with the oral
      Sabin vaccine promoted by the Health General Office. This simultaneity of
      campaigns was due to the interest that both bodies had to control the Preventive
      Medicine in Spain. The Compulsory Sickness Insurance used the anti-polio vaccine
      to promote itself socially in a time when the Basic Law on Social Security was
      being developed. Under these circumstances, the Health General Office allegedly
      brought forward its vaccine campaign by using a test of an innovative oral
      trivalent vaccine in the province of Leon, something which was hidden to the
      public. The Health General Office's claim of competence in prevention and the
      need of a massive response to a voluntary vaccine led to a singular advertising
      campaign with old messages in innovative means of communication.

PMID- 19753684
TI  - [Use of specialists in cancer care].

PMID- 19753685
TI  - [To the Occupational Minister].

PMID- 19753686
TI  - [Consolidating the medical model of disability: on poliomyelitis and constitution
      of orthopedic surgery and orthopaedics as a speciality in Spain (1930-1950)].
AB  - At the beginning of the 1930s, various factors made it necessary to transform one
      of the institutions which was renowned for its work regarding the social
      reinsertion of the disabled, that is, the Instituto de Reeducacion Profesional de
      Invalidos del Trabajo (Institute for Occupational Retraining of Invalids of
      Work). The economic crisis of 1929 and the legislative reform aimed at regulating
      occupational accidents highlighted the failings of this institution to fulfill
      its objectives. After a time of uncertainty, the centre was renamed the Instituto
      Nacional de Reeducacion de Invalidos (National Institute for Retraining of
      Invalids). This was done to take advantage of its work in championing the
      recovery of all people with disabilities.This work aims to study the role played
      in this process by the poliomyelitis epidemics in Spain at this time. It aims to
      highlight how this disease justified the need to continue the work of a group of
      professionals and how it helped to reorient the previous programme to re-educate
      the "invalids." Thus we shall see the way in which, from 1930 to 1950, a specific
      medical technology helped to consolidate an "individual model" of disability and
      how a certain cultural stereotype of those affected developed as a result.
      Lastly, this work discusses the way in which all this took place in the midst of
      a process of professional development of orthopaedic surgeons.

PMID- 19753687
TI  - [Ethics in medical every day practice: why and how?].

PMID- 19753688
TI  - Costs of treatment for age-related macular degeneration.

PMID- 19753689
TI  - Polio chronicles: warm springs and disability politics in the 1930s.
AB  - During the 1920s and 1930s, disabled polio survivors initiated a campaign which
      made them active, dissenting subjects in public discourse about disease and
      disability. Its source was a core of Warm Springs patients who wanted more than a
      healing refuge. They were well aware of the need to construct a new image of the
      disabled, and saw the resort's high public profile as a potent weapon in a
      cultural war to remake popular images of the disabled, whether as pathetic
      charitable objects or as horrific movie villains. Drawing on their own,
      disheartening experiences, this group of activists boldly critiqued the medical
      care offered most disabled patients as well as the training and attitudes of
      doctors, nurses and physical therapists. Protesting the narrow, medicalized
      definition of rehabilitation, they provocatively posed the need to "rehabilitate"
      prejudiced, able-bodied employers and health professionals. And most of all, they
      consciously designed the polio center at Warm Springs to function not as an
      inward-looking refuge but as an exemplar of the way polio survivors and other
      disabled people should be allowed to live, work and love. This story begins and
      ends in the 1930s. It traces a rise and fall: the rise of an activist community
      at the rehabilitative center at Warm Springs; and its decline with the creation
      of the National Foundation for Infantile Paralysis (known popularly as the March
      of Dimes) in 1937.

PMID- 19753690
TI  - Abstracts of the American Society for Laser Medicine and Surgery 29th Annual
      Conference, April 1-5, 2009.

PMID- 19753691
TI  - And they shall walk: ideal versus reality in polio rehabilitation in the United
      States.
AB  - This essay explores the significance that rehabilitation physicians and polio
      patients in the United States put on recovering the ability to walk. Polio often
      paralyzed or severely weakened the legs of those who contracted the disease.
      Regaining the ability to walk was thus a significant measure of recovery from the
      disease. However, walking meant more than the physical act itself. Regaining the
      ability to walk meant, in a symbolic sense, that one was no longer disabled, that
      one had again become normal. This attitude was shared by rehabilitation
      specialists and patients alike. This essay examines this attitude and the
      cultural values it embodied through a study of the efforts of selected polio
      survivors to learn to walk again and of the rehabilitation literature that held
      walking as an ideal. It also explores what happened when polio patients were
      unable to walk again because of the severity of their paralysis.

PMID- 19753692
TI  - Special issue editorial: The changing face of health informatics and health
      information management.

PMID- 19753693
TI  - "Pur sarripu pursa trutin": monster-fighting and medicine in early medieval
      Scandinavia.
AB  - This paper seeks evidence among our extensive Scandinavian mythological texts for
      an area which they seldom discuss explicitly: the conceptualisation and handling
      of illness and healing. Its core evidence is two runic texts (the Canterbury Rune
      Charm and the Sigtuna Amulet) which conceptualise illness as a "purs" ("ogre,
      monster"). The article discusses the semantics of "purs," arguing that illness
      and supernatural beings could be conceptualised as identical in medieval
      Scandinavia. This provides a basis for arguing that myths in which gods and
      heroes fight monsters provided a paradigm for the struggle with illness.

PMID- 19753694
TI  - Anesthetic and cardiopulmonary effects of propofol in dogs premedicated with
      atropine, butorphanol, and medetomidine.
AB  - This study evaluated the anesthetic and cardiorespiratory effects of a
      combination of intravenous propofol (2.2 mg/kg), intramuscular medetomidine (22.0
      pg/kg), intravenous butorphanol (0.22 mg/kg), and intravenous atropine (0.022
      mg/kg) in healthy dogs. Anesthesia was characterized by muscle relaxation and
      analgesia. Heart rate decreased after medetomidine and propofol administration
      (131 to 113 beats/min) but returned to baseline after intravenous atipamezole
      (110 microg/kg). Mild acidemia, hypercapnia, hypoxemia, and decreased SaO2
      developed after premedication. PaO2 and SaO2 were further decreased by propofol
      injection. In conclusion, this combination proved to be an effective anesthetic
      protocol for healthy dogs and should be adequate for minor surgical procedures.

PMID- 19753695
TI  - Effect of diet on hunting performance of English pointers.
AB  - A study was conducted to evaluate the influence of diet on hunting performance of
      English pointers during the quail-hunting season in southwest Georgia. Twenty
      three trained dogs were assigned to two commercially available diets (i.e., Diet
      A = Eukanuba Premium Performance Formula, The Iams Company, Lewisburg, OH; Diet B
      = Diamond Premium Adult Dog Food, Diamond Pet Foods, Meta, MO). Results showed
      that dogs fed Diet A maintained or gained weight and body condition throughout
      the hunting season while dogs fed Diet B lost body weight and body condition (P <
      .05). Dogs fed Diet A demonstrated superior hunting performance (P < .05)
      compared with those fed Diet B based on total finds per hunt and on the number of
      birds located per hour of hunting. All blood variables were within normal ranges
      for adult healthy dogs throughout the season. These results imply that diet can
      affect the overall performance of hunting dogs and should provide useful
      information to trainers, handlers, and clinicians who are concerned with
      promoting the best performance and health in hunting dogs and other canine
      athletes.

PMID- 19753696
TI  - A noncomparative open-label study evaluating the effect of selegiline
      hydrochloride in a clinical setting.
AB  - Six hundred forty-one dogs with clinical signs consistent with canine cognitive
      dysfunction syndrome (CDS) were treated orally with selegiline hydrochloride at
      0.5 to 1.0 mg/kg once daily for 60 days. Response to selegiline treatment on days
      30 and 60 were similar. On day 60, 77.2% of dogs showed an overall improvement;
      response to treatment by clinical sign ranged from 67.8% (activity or sleep/wake
      cycle) to 77.8% (disorientation and interaction with family members). All dogs
      enrolled in the study were monitored for possible adverse events; diarrhea
      (4.2%), anorexia (3.6%), and vomiting/salivation (3.4%) were noted most
      frequently. Results of this study indicate the majority of the dogs with CDS
      responded to treatment with Anipryl by day 30.

PMID- 19753697
TI  - Fasciola hepatica: a review of the economic impact in cattle and considerations
      for control.
AB  - To understand the rationale behind recommended control programs for liver flukes
      in cattle, the economic impact and the complex life cycle of Fasciola hepatica
      need to be appreciated. Fluke-infected cattle rarely demonstrate clinical
      disease, but subclinical impairment of feed efficiency, growth, and fertility can
      have an important impact on productivity. Although the precise benefit from
      controlling liver flukes is unknown due to the inherent variability between
      studies, most investigations demonstrate a considerable economic advantage to
      treatment. In addition, recent studies have demonstrated that liver flukes may
      cause a decrease in host fertility by altering normal metabolism and/or balance
      of sex hormones. This review focuses on these issues and how to best use
      available drugs to implement optimal fluke control programs.

PMID- 19753698
TI  - Efficacy of intramuscular tylosin for the treatment and control of porcine
      proliferative enteropathy caused by Lawsonia intracellularis.
AB  - This double-blind study investigated the efficacy of injectable tylosin (Tylan
      200 injection, Elanco Animal Health, Indianapolis, IN) for the treatment and
      control of porcine proliferative enteropathy caused by Lawsonia intracellularis
      using a mucosal challenge model. Intramuscular (IM) tylosin was compared with
      sterile tylosin injection carrier (negative control). IM treatments (1 mL/22.5 kg
      [50 lb body weight; 4 mg/lb body weight]) were administered to two groups of pigs
      twice daily for 3 consecutive days, commencing 14 days after L. intracellularis
      challenge. Clinical signs were evaluated in 80 pigs each day for 14 days after
      treatment was initiated. Necropsies were performed on all pigs 14 days after
      treatment to evaluate gross and microscopic intestinal lesions. The challenged
      pigs had a positive treatment response to injectable tylosin compared with
      negative controls based on improvements in clinical signs, fecal polymerase chain
      reaction incidence on days 7 and 14, gross and microscopic intestinal lesions,
      average daily weight gain, and individual pig weight variation.

PMID- 19753699
TI  - Influence of diet on urinary pH, urine and serum biochemical variables, and blood
      ionized calcium concentrations in healthy dogs.
AB  - Urolithiasis is a common cause of lower urinary tract disease in dogs. Diet
      influences urine composition, and dietary change is often incorporated into
      medical management of uroliths. The purpose of this study was to determine the
      influence of four diets on urine pH in healthy dogs. Sixteen adult dogs of
      various breeds, ages, and weights were fed four diets in Latin Square design: a
      diet formulated for adult dogs at maintenance (Diet A; ProPlan Canine Chicken and
      Rice Adult [dry], Ralston Purina Co, St. Louis, MO); a diet formulated to aid in
      management of fiber-responsive diseases (Diet B; CNM Canine DCO [dry], Ralston
      Purina Co, St. Louis, MO); a diet formulated to aid in management of chronic
      renal failure (Diet C; CNM Canine NF [dry], Ralston Purina Co, St. Louis, MO);
      and a diet designed to aid in prevention of struvite urolithiasis (Diet D;
      Prescription Diet Canine c/d [dry], Hill's Pet Nutrition Inc, Topeka, KS). Diets
      were fed for 21 days. On day 21, blood and urine samples were collected before
      feeding one-half of daily caloric requirements, and urine was collected 4 and 8
      hours later. A biochemical analysis and ionized-calcium test were conducted on
      blood samples, and a complete urinalysis and urine pH determined by a pH
      electrode were conducted on urine samples. Thirteen dogs completed the study.
      Serum phosphorous concentrations were significantly lower and urine pH was
      significantly higher when dogs consumed Diet C when compared with the other three
      diets. A postprandial effect on urine pH was not demonstrated when dogs consumed
      any diet. Other urinalysis parameters were not different between dogs or diets.
      Diet does influence urine pH in healthy dogs; however, healthy dogs produced
      urine with an acidic pH except while consuming a diet specifically formulated to
      produce alkaluria. Furthermore, crystalluria was commonly found in these healthy
      dogs regardless of the diet.

PMID- 19753700
TI  - Effect of ascorbate and two different media on canine chondrocytes in three
      dimensional culture.
AB  - The objective of this study was to determine the effects of ascorbate and two
      different culture media on cell morphology and extracellular matrix formation of
      canine chondrocytes grown in a three-dimensional (3-D) culture system. Articular
      cartilage harvested from the humeral head of three adult canine cadavers was used
      to obtain chondrocytes for primary culture. Subcultured chondrocytes were seeded
      in a 3-D medium of RPMI-1640 (R), RPMI-1640 with 50 microg/mL ascorbate (RA),
      Ham's F-12 (F), or Ham's F-12 with 50 microg/mL ascorbate (FA) in agarose.
      Samples were harvested at 5, 10, 15, and 20 days of 3-D culture and analyzed for
      histologic appearance and proteoglycan staining, electron microscopic appearance,
      dimethylmethylene blue assay for glycosaminoglycan (GAG) content, and
      immunohistochemical staining for collagen type II production. Chondrocytes in all
      four groups maintained appropriate morphology and produced matrix over the entire
      study period. Chondrocytes from groups R and RA produced more GAG and collagen
      type II than did those from groups F and FA on days 10 (P = .00791) and 15 (P =
      .0173). Chondrocytes from group RA produced more GAG on days 5 (P = .0154) and 20
      (P = .0044) than did those in groups R, F, and FA. With respect to matrix
      production, RPMI-1640 is superior to Ham's F-12 for 3-D culture of canine
      chondrocytes. The addition of ascorbate at 50 microg/mL to RPMI-1640 did have a
      positive effect on the production of GAG but had minimal effect on type II
      collagen production. Determining the most ideal in vitro microenvironment for
      canine chondrocytes grown in a 3-D culture system has important implications to
      the in vivo application of this technique.

PMID- 19753701
TI  - 1999 guidelines for the diagnosis, treatment, and prevention of heartworm
      (Dirofilaria immitis) infection in cats.

PMID- 19753702
TI  - Influence of green lipped mussels (Perna canaliculus) in alleviating signs of
      arthritis in dogs.
AB  - This study evaluated the efficacy of green lipped mussel (GLM), added to a
      complete dry diet, for alleviating clinical signs of arthritis in dogs. A double
      blind longitudinal study design was used with 31 mixed-breed dogs exhibiting
      varying degrees of arthritis. Each dog was evaluated by a veterinarian and joints
      were individually scored for degree of pain, swelling, crepitus, and reduction in
      range of movement. Summation of all scores for an individual dog comprised its
      total arthritis score. At baseline, dogs were randomly allocated to control and
      test groups. Both groups were fed the same base dry diet, to which 0.3% GLM
      powder was added for dogs in the test group. The change in total arthritis score
      by the end of 6 weeks showed there was significant improvement (P < .05) in the
      test group versus the control group. Significant improvements were also observed
      in joint pain and swelling scores in the test group. Changes in joint crepitus
      and range of joint movement were not significantly different between the test and
      control groups. These findings provide strong evidence that GLM incorporated into
      a complete dry diet can help alleviate arthritis symptoms in dogs.

PMID- 19753703
TI  - Efficacy of porcine reproductive and respiratory syndrome virus vaccine and
      porcine interleukin-12.
AB  - The efficacy of porcine recombinant interleukin-12 (prIL-12) as an adjuvant to
      stimulate immunity was investigated in pigs vaccinated against porcine
      reproductive and respiratory syndrome virus (PRRSV). Porcine recombinant IL-12
      was cloned and expressed in the insect baculovirus system. Thirty pigs were
      randomly allocated to five groups, and individual pigs were injected with PRRSV
      modified live virus with and without coadministration of prIL2; PRRSV killed
      virus with and without coadministration of prIL-12; or prIL-12 only (control).
      The effect of prIL-12 was evaluated through monitoring of humoral and cell
      mediated immune (CMI) responses. Results indicated that the killed virus given in
      conjunction with prlL-12 induced humoral and CMI responses of similar magnitude
      to those of the modified live virus. However, without prIL-12, the immunologic
      response to vaccination with the killed virus vaccine was poor and similar to
      that of controls.

PMID- 19753704
TI  - Tissue concentrations of enrofloxacin and ciprofloxacin in anesthetized dogs
      following single intravenous administration.
AB  - Concentrations of enrofloxacin and its active metabolite, ciprofloxacin, were
      detected in tissues following single intravenous administration of 20 mg/kg to
      four anesthetized dogs. Two hours after treatment, serum samples were collected,
      animals were euthanized, and tissues were collected from each dog. Solid tissues
      were homogenized, and both enrofloxacin and ciprofloxacin were detected using
      high-performance liquid chromatography. Enrofloxacin was detected in all tissues
      examined; the highest concentrations were found in the gall bladder, urine, bile,
      stomach, and liver. Concentrations in the cerebral cortex, cerebrospinal fluid,
      skin, and prostate were 5.7, 5.3, 9.2, and 23.5 microg/ml, respectively. Tissues
      for which the concentration of enrofloxacin was 4 microg/ml or lower included the
      trachea, articular cartilage, aqueous humor, fat, and tendon. An inhibitory
      quotient of 8 or more was achieved for enrofloxacin in the majority of tissues
      studied. Ciprofloxacin was detected in 29 of 40 tissues examined.

PMID- 19753705
TI  - Pharmacokinetics of the bovine formulation of enrofloxacin (Baytril 100) in
      horses.
AB  - Following approval of a concentrated injectable formulation of enrofloxacin for
      cattle (Baytril 100 Injectable, Bayer Corp. Agricultural Division, Shawnee
      Mission, KS), equine practitioners have started administering this preparation
      both parenterally and orally to horses, despite the lack of pharmacokinetic data
      in this species. Six healthy horses received enrofloxacin at 7.5 mg/kg both
      orally and intravenously, with the sequence being randomly assigned and at least
      1 week of washout allowed between administrations. Blood samples were collected
      from each horse at various intervals after drug administration to study the
      pharmacokinetic profile of this product. As concentration-dependent
      antimicrobials, fluorinated quinolones such as enrofloxacin are most efficacious
      when the inhibitory quotient is at least 8. In this study, based on inhibitory
      quotients between 8 and 10, the bovine injectable formulation of enrofloxacin
      administered to horses intravenously or orally once daily at 7.5 mg/kg may be
      effective against susceptible organisms whose minimum inhibitory concentration
      for 90% of the isolates is lower than 0.5 microg/ml.

PMID- 19753706
TI  - Efficacy of a topical spot-on containing 65% permethrin against the dog louse,
      Trichodectes canis (Mallophaga:Trichodectidae).
AB  - The efficacy of a 65% permethrin spot-on formulation (Defend EXspot, Schering
      Plough Animal Health Corp., Union, NJ) against the dog louse, Trichodectes canis
      de Greer 1778, was studied. Fourteen dogs naturally infested with T. canis were
      evenly and randomly allocated to treatment with 65% permethrin administered at
      the label dose rate of 1 or 2 ml per dog or to an untreated control group. Louse
      counts were performed for each dog by gently back-combing the hair at six
      designated anatomic sites (head, tail, belly, each side, and an 8-cm strip the
      length of the body on the back), and lice were counted without removal on Days 0
      (pretreatment), 7, 14, 21, and 28. Lice were eliminated from all dogs treated
      with the 65% permethrin spot-on within 7 days after treatment, and no subsequent
      reinfestations due to hatching of eggs were observed during the 28-day evaluation
      period. Untreated control dogs were subsequently treated with the 65% permethrin
      spot-on after the initial phase was completed and lice populations were evaluated
      as previously described. All lice were cleared from these dogs by Day 7, and
      there were no signs of reinfestation. No adverse reactions to treatment were
      noted during the study.

PMID- 19753707
TI  - Electrolyte replacement in urban search and rescue dogs: a field study.
AB  - Urban search and rescue (USAR) dogs provide an important service in search,
      patrol, and explosive detection in urban and natural disasters. These dogs are
      exposed to stressful and dangerous conditions that can lead to dehydration and
      electrolyte imbalances. Oral electrolyte and carbohydrate supplementation
      decreases electrolyte disturbances and improves endurance in other animal
      species. A field study was performed to determine the effect of oral electrolyte
      supplementation on performance and electrolyte balance of USAR dogs performing
      moderate-intensity work. Nine Pennsylvania Task Force 1 USAR dogs were randomly
      assigned to water or electrolyte replacement solution (Electramine, Vitae Inc.,
      Breckenridge, CO) on two separate training days, one in winter and one in summer.
      There was no clinically significant or repeatable improvement in plasma
      electrolyte composition or performance in electrolyte-supplemented dogs. Although
      other electrolyte formulations must be tested to determine potential benefits,
      the overall benefits of electrolyte supplementation do not seem to outweigh the
      expense and burden of including these replacement fluids in USAR gear.

PMID- 19753708
TI  - Oral treatment with a nutraceutical (Cosequin) for ameliorating signs of
      navicular syndrome in horses.
AB  - Fourteen horses with a progressive forelimb lameness of 3 to 12 months' duration,
      diagnosed as navicular syndrome, were selected from clinical cases admitted to
      Auburn University Equine Hospital for evaluation of the efficacy of an orally
      administered nutraceutical (Cosequin, Nutramax Laboratories, Inc., Edgewood, MD)
      for ameliorating clinical signs associated with naturally occurring navicular
      syndrome. Horses were randomly allocated to treatment with the nutraceutical or a
      placebo. Treatment was five scoops (16.5 g) of powder twice daily in the feed.
      The test group (n = 8) received a patented nutraceutical consisting of 9 g of
      FCHG49 (a highly purified glucosamine HCl), 3 g of TRH122 (a specific purified
      low-molecular-weight sodium chondroitin sulfate), and 600 mg of manganese
      ascorbate. The placebo group (n = 6) received an indistinguishable oral powder
      containing only excipients. Owners and the investigator were unaware of group
      assignments. The same investigator assessed lameness and overall clinical
      condition at enrollment and after 4 and 8 weeks of treatment. Lameness was
      assessed by an algofunctional lameness index, comprising a combined sum score of
      standing posture, hoof tester examination, and lameness scores at various levels
      of work. Overall clinical efficacy was rated on a visual analogue scale. Owners
      assessed lameness via a preassigned questionnaire, incorporating an
      algofunctional lameness index and overall clinical condition at weekly intervals.
      Radiographic examinations of the navicular bones were performed at enrollment and
      after 8 weeks of treatment. The median algofunctional lameness index and overall
      clinical condition scores assigned the investigator were significantly improved
      (P = .05) for horses treated with the nutraceutical compared with placebo-treated
      horses. The degree of improvement in algofunctional lameness index assigned by
      owners after 8 weeks was also significant (P = .045) between the treatment
      groups. Radiographic scores after treatment were not significantly different
      between the groups (P > .05).

PMID- 19753709
TI  - Glucose tolerance and lipid profiles in dogs fed different fiber diets.
AB  - Increased dietary fiber is thought to have beneficial effects on health in
      humans. In diabetic dogs, a beneficial effect of fiber on glycemia has been
      suggested, while its effect on lipid profiles in dogs has not been described. The
      effects of different amounts and types of fiber on glucose tolerance and lipid
      concentrations were evaluated and compared with those of a standard maintenance
      ration in 30 healthy dogs. It was concluded that increased fiber intake had no
      influence on glucose in healthy dogs but it may have modulated lipid homeostasis.

PMID- 19753710
TI  - Evaluation of the speed of kill of fleas and ticks with Frontline Top Spot in
      dogs.
AB  - The speed of kill of a spot-on formulation of fipronil (Frontline Top Spot,
      Merial Limited, Duluth, GA) against adult cat fleas (Ctenocephalides felis) and
      brown dog ticks (Rhipicephalus sanguineus) was evaluated in dogs in a commercial
      laboratory setting. Forty dogs were allocated to 20 replicates of two based on
      sex and pretreatment flea counts. Within each replicate, dogs were randomly
      allocated to an untreated control group or to treatment with fipronil,
      administered topically as a spot-on per label instructions. The technical staff
      performing the flea and tick counts were unaware of treatment group assignments.
      Each dog was infested with approximately 100 unfed adult fleas on Day -8 or -6
      and on Day -1. Each dog also was infested with approximately 50 unfed adult ticks
      on Day -1. Treatments were administered on Day 0 according to body weight. Flea
      and tick counts were performed on four randomly selected dogs from each treatment
      group at approximately 6, 12, 18, 24, and 48 hours after treatment. Flea and tick
      count reductions for dogs treated with fipronil were significant (P < .05), as
      compared with untreated controls, at 18, 24, and 48 hours after treatment.
      Controlled efficacy of fipronil against C. felis and R. sanguineus ranged from
      94% to 100% at these evaluation times. This study demonstrated that the speed of
      kill of fipronil, applied topically as a spot-on, was 100% against C. felis fleas
      on dogs within 12 to 18 hours after treatment and 100% against R. sanguineus
      ticks between 24 and 48 hours after treatment.

PMID- 19753711
TI  - [The Dr. Francisco Montes de Oca National Prize for Surgery].

PMID- 19753712
TI  - [Microvascular decompression for hemifacial spasm. Ten years of experience].
AB  - INTRODUCTION: Hemifacial spasm characterized by involuntary paroxistic
      contractions of the face is more frequent on left side and in females. Evolution
      is progressive and in a few cases may disappear. Management includes medical
      treatment, botulinum toxin, and microvascular decompression of the nerve.
      MATERIAL AND METHODS: We present the results of 116 microvascular decompressions
      performed in 88 patients over 10 years. RESULTS: All patients had previous
      medical treatment. All patients were operated on with microsurgical technique by
      asterional craniotomy. Vascular compression was present in all cases with one
      exception. Follow-up was from 1 month to 133 months. Were achieved excellent
      results in 70.45% of cases after first operation, good results in 9.09%, and poor
      results in 20.45% of patients. Long-term results were excellent in 81.82%, good
      in 6.82%, and poor in 11.36% of patients. Hypoacusia and transitory facial palsy
      were the main complications. DISCUSSION: Hemifacial spasm is a painless but
      disabling entity. Medical treatment is effective in a limited fashion. Injection
      of botulinum toxin has good response but benefit is transitory. Microvascular
      decompression is treatment of choice because it is minimally invasive, not
      destructive, requires minimum technical support, and yields best long-term
      results.

PMID- 19753713
TI  - [Commentary on the work entitled: "Microvascular decompression for hemifacial
      spasm. Ten years of experience"].

PMID- 19753714
TI  - [Surgical treatment results of 52 cases of temporomandibular ankylosis].
AB  - We courried out a retrospective study of 52 surgical cases of temporomandibular
      joint ankylosis, fibrous types I and II in 19 patients (36.4%) and osseous type
      III-IV in 33 patients (63.6%). Forty two children and teenagers at the Hospital
      de Pediatria (1983-1985/1989-1998) and Hospital General La Raza (1985-1989) were
      included also, 10 adults including those operated on at the Hospital de
      Especialidades, CMN Siglo XXI (IMSS) from 1998 to 2001 were included. We used
      Dunn modified method en 37 cases (67%) and 17 patients were with Risdon operated
      on technique (33%). Etiology of ankylosis were direct trauma to jaw, which
      affected temporomandibular joint mainly in children, while in adults causes were
      more varied and included as osteomyelitis, middle ear infection, sequels of
      hemifacial microsomy, and trauma results were considered as good upon obtaining
      mouth opening of 35 mm without neo-ankylosis during 1-year postoperative control.

PMID- 19753715
TI  - [Commentary on the work entitled: "Surgical treatment results of 52 cases of
      temporomandibular ankylosis"].

PMID- 19753716
TI  - [Penetrating cardiac trauma. A nine-years experience in Cancun, Mexico].
AB  - INTRODUCTION: Early patient intubations, rapid transportation, thoracotomy in the
      emergency room, and tamponade are the main reasons why patients with cardiac
      trauma survive at present. This paper describes the experience with cardiac
      trauma in Cancun, Quintana Roo, Mexico, during period of 9 years by general
      surgeons. MATERIAL AND METHODS: This is a retrospective study at three regional
      hospital of 25 patients described by percentages and average. RESULTS: During a 9
      year period, 25 patients were studied, all male, ages ranged from 18-39 years; 11
      had right ventricle lesion, nine had left ventricle trauma, two of left atrium,
      and one case each of right atrium, superior vena cava, and superior left vein. No
      coronary lesions were observed. Four patients had post-traumatic pericarditis.
      Mortality was 20% (five patients). DISCUSSION: Cardiac trauma presents in a wide
      range of clinical situations. Tamponade was observed as a positive prognostic
      factor, mortality was due to principally lesions caused by firearms and to
      ascending aorta trauma. Extracorporeal circulation pump is rarely required.

PMID- 19753717
TI  - [Conservative management of postappendectomy intraperitoneal abscess. Preliminary
      results].
AB  - INTRODUCTION AND OBJECTIVES: For decades, prestigious authors of surgical texts
      have established that intraperitoneal abscess should be managed by laparotomy,
      drainage of pus, and antibiotics. However, availability of new and more powerful
      antimicrobials have allowed for other therapeutic modalities. MATERIAL AND
      METHODS: Thirty children in whom clinical or sonographic presence of purulent
      collection in peritoneal cavity as consequence of appendectomy were studied. With
      Ethical Committee and parental consent, we filled out the corresponding protocol.
      We decided to carry out pre-and post-test sonogram and administration of
      gentamycin 5-7 mg/kg/day or cefotaxime 100 mg/kg/day IV for 10-14 days. RESULTS:
      There was improvement in all cases within the first 72 h and curing during the
      second week. No patient required laparotomy. Employment of antimicrobials was
      curative.

PMID- 19753718
TI  - [Commentary on the work entitled: "Conservative management of postappendectomy
      intraperitoneal abscess. Preliminary results"].

PMID- 19753719
TI  - [Manual mechanical anastomosis colorectal surgery].
AB  - OBJECTIVE: To determine advantages and disadvantages of manual vs mechanical
      sutures in colon surgery. MATERIAL AND METHODS: A retrospective study of clinical
      files of 84 colon surgery patients was conducted, to establish morbidity and
      mortality of these patients with special emphasis in length of surgical procedure
      and type of suture used during procedure (either manual or mechanical). RESULTS:
      Of 84 patients included in this study, manual suture was used in 70 (group 1) and
      mechanical suture in 14 (group 2). Most common preoperative diagnosis was
      diverticular disease in 22 cases (26.2%), 20 for group with manual suture, and
      two for group with mechanical suture. Most common surgical procedure was
      colectomy with ileoproctoanastomosis in group 1 and lower anterior resection with
      coloproctoanastomosis in group 2. Five cases presented complications (2.85%) with
      manual suture, while only one case presented complications in group 2 (7.14%).
      Main complications were dehiscence in group 1 and stenosis in group 2.
      DISCUSSION: There were no significant differences between both types of suture in
      terms of time of surgical procedure; there were no statistical differences for
      both techniques in terms of morbidity and mortality. However, there is shorter
      time of recovery in patients in whom mechanical suture was used with less tissue
      edema due to manipulation and less disability period.

PMID- 19753720
TI  - [Simplified nutritional evaluation system for surgical patients].
AB  - OBJECTIVE: To determine a simplified method for nutritional status evaluation in
      surgical patients to identify patients prone to develop complications. METHODS: A
      prospective study was carried out to determine prognostic index of patients in
      whom major abdominal surgery was performed, based on nutritional assessment. We
      proposed a simplified and accessible method for daily evaluation of patients in
      any hospital even in an emergency setting. The following parameters were used:
      complete blood count (CBC); blood chemistry (BC); protrombine time (PT); total
      serum protein (TSP), and anthropometrics. RESULTS: Study population consisted of
      200 patients divided in two groups depending on type of surgical intervention,
      i.e., emergency or elective procedure. Complications associated with different
      stages of malnourishment were analyzed by simplified nutritional assessment
      system. Of 200 patients analyzed, 123 had several stages of malnutrition, 62 were
      malnourished, complicated patients (50.41%), and 77 had adequate nutritional
      status; of these, 10 also had complications (12.99%). DISCUSSION: We were able to
      conclude that simplified nutritional assessment system is not a useful absolute
      predictive indicator of possible complications. However, some parameters could be
      useful to identify patients with nutritional depletion with tendency for post
      surgical complications.

PMID- 19753721
TI  - [Ketorolac vs metamizol preemptive analgesia in children].
AB  - Preventive analgesia produced by ketorolac and metamizol was evaluated during a
      prospective study randomized in two groups. One hundred twenty children were
      included aged from 3 to 6 years who underwent surgery by different procedures.
      Analgesic dose was applied 15 min prior to surgery by intravenous (i.v.) via.
      Technique used was inhaled general anesthesia; use of opioids was avoided. Pain
      evaluation at the end of surgery (and during the following 48 to 72 h) as well as
      bleeding time, platelet count, and alterations in white blood cell count were
      dependent variables. As soon as patients arrived in the recovery room, pain was
      measured by modified McGrath scales and the chromatic EVA. In ketorolac group,
      40% of children showed no pain and 55% presented mild to moderate pain (1-6). In
      metamizol group, 40% of children referred no pain, while 55% evaluated pain as
      minimal to moderate. Analgesia produced by both drugs presented no significant
      statistical diference (p > 0.5). Troughout followup, maximum pain referred had a
      values of 6 and 7, respectively, for ketorolac and metamizol. Fifteen min after
      analgesic dose, pain was referred as 3 and 4. No alterations were observed in
      bleeding time, platelet count, and white blood cell count. We conclude that both
      analgesics prevent hyperalgesia during post-surgical period.

PMID- 19753722
TI  - [Bull horn wounds. A 1 year experience at the O'Horan General Hospital Merida,
      Yucatan, Mexico].
AB  - INTRODUCTION: Taurine medicine has been able to open the way to the advance of
      science and to the adaptation of science to the patient with a bull horn wound so
      that at present, 95% of patients now survive gorings that were fatal in earlier
      times. MATERIAL AND METHODS: We carried out a retrospective study, utilizing
      clinical files from the O'Horan General Hospital in Merida, Yucatan, Mexico
      during January 1999 through November 2000 as a data-base. RESULTS: Fifteen
      patients, all male, were treated for 26 bull horn goring wounds. The most
      frequently injuried patients ranged in age from 14-30 years. All patients were
      received at the Trauma Unit within 12 h of goring; gorings most frequently
      occurred in the town of Oxtcutzab, with from patients. Eight patients of is were
      bullfighters, all with different professions outside the bullfighting season;
      there were six spontaneous gorings, and the remaining patient was a cowboy
      wounded during work. Wounds of eight patients were closed, seven received open
      treatment. From time of admittance, all patients were administered a triple
      antibiotic schema, in addition to anti-tetanic gamma globulin and tetanic toxoid.
      DISCUSSION: We carried out comparisons with our patient bull horn goring
      treatments and those published in the Surgical Round, Spanish Surgery, and the
      Mexican Journal of Orthopedics and Traumatology; our results were similian to
      those found in the international literature.

PMID- 19753723
TI  - [Sclerosing encapsulated peritonitis. Diagnostic and therapeutic challenge for
      the general surgeon].
AB  - Intestinal obstruction is one of the most frequently abdominal problems that
      concern general surgeons. One of the infrequent causes of mechanical obstruction
      is sclerosing encapsulating peritonitis (SEP); this entity causes intense
      fibrosis of the components in the peritoneal layer, resulting in adhesion of
      abdominal organs. SEP can be primary or secondary; both are a type of peritoneal
      fibrosclerosis that causes intestinal obstruction with difficult resolution and a
      great number of complications. In terms of frequency and etiology, there are few
      data, and the problem is considerated a multifactorial disease with association
      to neoplasms, toxics, drugs, and idiopathic form. This article presents three
      cases of sclerosing encapsulating peritonitis and the possible factors that play
      an important role in the development of this infrequent entity.

PMID- 19753724
TI  - [West Nile fever].
AB  - West Nile fever is a mosquito-borne febrile illness seen in Africa, Asia, and
      Europe, but reported in North America only once. West Nile virus is of the family
      Flaviviridae, genus Flavivirus. Several West Nile fever outbreaks were reported
      from Israel in the 1950s and in 1980. Since the mid-1990s, frequency and apparent
      clinical severity of West Nile virus outbreaks have increased. Outbreaks in
      Rumania (1996), Russia (1999), and Israel (2000) involved hundreds of persons
      with severe neurologic disease. In the summer of 1999, West Nile virus was
      recognized in the among Western Hemisphere for the first time when it caused an
      epidemic of encephalitis and aseptic meningitis among residents of greater New
      York City. Other outbreak occurred during the summer of 2000. West Nile fever in
      humans usually is a febrile, influenza-like illness characterized by abrupt
      onset. Occasionally (less than 15% of cases) are acute aseptic meningitis or
      encephalitis. Although human vaccines for West Nile virus are under development,
      the most effective to way reduce local population of mosquitoes is to eliminate
      sources of standing water and preventing vector mosquitoes from biting humans by
      using mosquito repellents and barrier methods.

PMID- 19753725
TI  - [A historic sentence].

PMID- 19753726
TI  - [Speech for closing of the 69th Academic Year of the Mexican Academy of Surgery].

PMID- 19753727
TI  - [Two Japanese pearls in the interpretation of the Quixote and in the translation
      of Hamlet].

PMID- 19753728
TI  - IAPs: the last choice to survive.
AB  - Caspases are harmful intracellular proteolytic enzymes that regulate the cellular
      suicide. A decade after the discovery of the first caspase an impetuous work from
      many different labs has endorsed to open our eyes on the complex mechanisms that
      are responsible for the strictly regulated control of their activity. This
      research area is not only a wonderland for biologists; an important outcome of
      these studies is that alterations in the newly identified molecular elements are
      responsible for different human diseases from neurodegeneration to cancer. This
      article reviews the molecular mechanisms regulating the formation/activity of the
      apoptosome, the central engine of the cell death machinery and in particular the
      function of the Inhibitor of Apoptosis Proteins IAPs.

PMID- 19753729
TI  - Autologous stem cell transplantation for Hodgkin's lymphoma: results and
      prognostic factors in 51 high-risk patients.
AB  - Autologous stem cell transplantation (ASCT) is largely employed in primary
      resistant or recurrent Hodgkin's Lymphoma (HL), while its role early in the
      course of the disease is still controversial. Our purpose was to analyse the
      results of 51 high-risk HL patients autografted at our Institution and the role
      of possible prognostic risk factors for the outcome. Twelve (23.5%) patients were
      in complete remission at transplant and were transplanted as having an high risk
      disease; 20 (39.5%) patients were in partial response and 19 (37.0%) were
      transplanted as primary induction failure. At a median time of 38 (6-111) months
      from ASCT, 36 (70.5%) patients are alive in complete remission, 8 (15.5%)
      patients are alive with disease and 7 (14.0%) died for progression. Thirty out of
      32 (94.0%) patients transplanted with responsive disease (either complete or
      partial response) are alive without disease. Six out of 19 (32.0%) patients
      transplanted with resistant disease are alive in complete remission. The overall
      survival of the entire population is 77.0% at 60 (14-151) months from diagnosis.
      Disease free survival of the 22 patients that achieved a complete remission after
      ASCT (16 in partial response and 6 with resistant disease) is 100%. In our
      experience, more than 90% of patients transplanted with responsive but high risk
      disease, seem achieving and maintaining a durable complete remission, and more
      than 30.0% of patients submitted to ASCT with refractory disease can be
      potentially rescued by transplant.

PMID- 19753730
TI  - Androgen receptor levels in the sebaceous glands of papulopustular lesions from
      patients with Behcet's disease and acne vulgaris: a controlled study.
AB  - AIMS: Male sex and a younger age of onset in Behcet's disease (BD) are associated
      with more severe disease. Eye diseases, folliculitis and thrombophlebitis are
      also more common among males. The disease rarely developes before puberty or
      after the age of 50. Clinical manifestations of BD, with the exception of eye
      symptoms, tend to get better with time. Clinical and histological pattern of the
      papulopustular lesions (PPL), the most common type of skin lesions in BD and the
      difference from ordinary acne is contradictory. Therefore, BD may be androgen
      driven to some degree. In the present study, using acne vulgaris (AV) as a
      prototype of an androgen driven disease, we investigated such a possibility
      between PPL and androgen receptor (AR) levels in the sebaceous glands (SG) of PPL
      from patients with BD and AV. METHODS: Eighteen patients with BD (10 women, 8
      men; mean +/- SD age, 34 +/- 11 years), 16 patients with AV (10 women, 6 men;
      mean +/- SD age, 25 +/- 6.2 years), and 10 healthy volunteers (5 women, 5 men;
      mean +/- SD age, 36 +/- 12 years), were included in this controlled study with
      blind histological study. Biopsies of the PPL and adjacent (approximately 2 cm
      distant) normal-appearing skin in patients with BD and AV, and of the normal
      appearing skin from healthy volunteers were performed from the interscapular
      region, thus minimizing differences in androgenic activity. Follicle-based
      acneiform lesions were excluded for biopsies from patients with BD. Nuclear AR
      levels of SG were studied by an immunohistochemical technique, using monoclonal
      antibodies. The percentage of positively staining cells were recorded as the
      androgen receptor index (ARI). MAIN RESULTS: The lesional skin of the patients
      with BD showed a higher ARI than non-lesional skin of those patients (34.3% and
      23.82%), or the healthy controls (21.37%). AR levels in the lesional skin of
      active patients was also higher than inactive patients (39.82 and 27.12%), but
      the differences were not statistically significant. ARI values in the lesional
      skin (78.58%) of acne patients were found to be significantly higher as compared
      with non-lesional skin (38.88%) and other groups (p<0.01). CONCLUSION: Our
      findings indicate that androgens may play a role at least in the formation of PPL
      and disease activity in patients with BD. Androgen metabolism takes place
      peripherally in the SG, being indipendent of the central endocrine regulation.
      Target organ sensitivity and excess number of nuclear AR seem to be responsible
      for the development of AV.

PMID- 19753731
TI  - Morphometric analysis of AgNORs in the lymph node lesions.
AB  - Silver stained argyrophilic nucleolar organizer regions (AgNOR) had widely been
      used for diagnostic as well as prognostic purposes in surgical pathology. Our
      study was carried out for the quantitative and morphometric analysis of AgNORs in
      various lymph node lesions. Ten cases each of reactive lymphadenitis and non
      Hodgkin's lymphoma (NHL) were included in the present study. Out of 10 cases of
      NHL, 5 cases each were of Low grade and High grade lymphomas. The morphometric
      analysis and quantification of AgNORs were curried out using a specific programme
      of an automatic image analysis Biovis Image measure version 1.0. The results
      revealed that mean AgNOR count was maximum in high grade lymphoma (5.17 +/-
      0.255) when compared with low grade lymphoma (4.78 +/- 0.41) and reactive lymph
      nodes (2.45 +/- 0.486). Similarly, the mean of total AgNOR area in high grade
      lymphoma (511.9 +/- 41.52) was highest followed by low grade lymphoma (451.12 +/-
      37.1) and reactive lymphadenitis (215 +/- 37). However, the mean of ratio of
      single AgNOR dot area to nuclear area was lowest in high grade lymphoma (0.0718
      +/- 0.01) in comparison to low grade lymphoma (0.0826 +/- 0.0096) and reactive
      lymph node (0.132 +/- 0.01). Thus, it can be concluded from the present study
      that different features of AgNOR evaluated morphometrically (AgNOR count, total
      AgNOR area, AgNOR dot area, ratio of total AgNOR area and single AgNOR area to
      nuclear area) were significantly altered in various lymph node lesions which may
      be helpful in differential diagnosis of problematic cases.

PMID- 19753732
TI  - Inflammation can be present in infantile congenital cystic adenomatoid
      malformation of the lung.
AB  - Congenital cystic adenomatoid malformation (CCAM) of the lung is characterized by
      an excessive overgrowth of the terminal respiratory bronchioles, probably of
      hamartomatous origin. The absence of inflammation has generally been considered
      obligatory for the diagnosis of CCAM of the lung in the infantile period.
      Furthermore, it has been argued that chronic inflammation itself may influence
      the development of cystic lesions within lung parenchyma. We report a case of an
      11-month-old infant with CCAM malformation of the lung type III associated with a
      super-impossed purulent inflammation and abscess formation. In conclusion, our
      case clearly demonstrates that CCAM may even in infantile period become inflamed,
      manifesting itself with different clinical symptoms and signs, such as
      respiratory distress or recurrent pneumonia.

PMID- 19753733
TI  - A case report of Sertoli cell tumor in a patient with testicular feminization:
      many dilemmas for the pathologist.
AB  - AIMS: The aim of this case report is to present the pathological, clinical, and
      ethic problems due to the diagnosis of an adnexal mass in a female patient with
      an undetected androgen insensitivity syndrome. METHODS: We employed both commonly
      used pathologic techniques, such as hematoxylin-eosin staining and
      immunohystochemistry, both fluorescence in situ hybridization on paraffin
      embedded tissue sections using probes for chromosomes X and Y. MAIN RESULTS: At
      pathologic evaluation, a diagnosis of Sertoli cell tumor was made. Fluorescence
      in situ hybridization showed an XY karyotype of tumor cells. The final diagnosis
      was bilateral Sertoli cell adenoma in a patient with testicular feminization
      syndrome. CONCLUSION: Androgen insensitivity syndrome is caused by insensitivity
      of end organs to androgen caused by a non-functioning receptor. The diagnosis of
      testicular feminization has been made as late as the ninth decade. In this case,
      two kinds of problem derived from the pathologist point of view: first, the
      demonstration of chromosomal sex to confirm the diagnosis, and second, the
      transfer of diagnosis to the patient and to the clinicians.

PMID- 19753734
TI  - Phototherapy of photodermatoses.
AB  - Phototherapy and photochemotherapy (PUVA therapy) have revolutionized the
      treatment of many photodermatoses and can offer photosensitive patients an
      improved quality of life. This is especially the case for polymorphic light
      eruption, chronic actinic dermatitis, erythropoietic protoporphyria and solar
      urticaria.

PMID- 19753735
TI  - Chemical avulsion with urea nail lacquer.
AB  - BACKGROUND: Among the therapeutic possibilities for onychomycosis, chemicalnail
      avulsion is a logical approach to the eradication of the pathogen. METHODS: A new
      formulation was used as a nail lacquer containing 40% urea in a film-forming
      solution in 10 patients presenting with onychomycosis. The urea nail lacquer was
      applied with a brush twice a day for 1 week by the patient and for a further week
      in two patients presenting total dystrophic onychomycosis. RESULTS: This
      transungual delivery system weakens the nail plate/nail bed attachment in the
      diseased area. CONCLUSION: The urea nail lacquer is comfortable for the patient
      and allows easy removal of the affected part of the fungal nail plate.

PMID- 19753736
TI  - Levothyroxine versus ketotifen in the treatment of patients with chronic
      urticaria and thyroid autoimmunity.
AB  - BACKGROUND: Thyroid hormone replacement therapy has previously been discussed as
      a feasible therapeutic approach in patients with chronic urticaria and/or angio
      oedema (CUA) and thyroid autoimmunity (TA). OBJECTIVE: The efficacy of
      levothyroxine was investigated in patients with CUA and TA by comparing it with
      ketotifen treatment. METHODS: A total of 60 patients with CUA and TA were
      included in the study. Patients were divided into two groups, which were matched
      with respect to sex, age and symptom score. Each group consisted of 30 patients.
      Patients in one group were treated with ketotifen and the other with
      levothyroxine. After completion of the treatment periods, the pre- and post
      treatment symptom scores, onset time of drug effects, duration of symptom-free
      period, recurrence ratios, recurrence times and side effects were evaluated for
      each drug. The two drugs were compared with each other according to these
      parameters. RESULTS: Ketotifen treatment provided significant relief of symptoms.
      However, these beneficial effects were observed only in ongoing treatment.
      Symptoms reappeared in all patients during the drug-free follow-up period. On the
      other hand, 18 of 30 patients were completely improved and three patients
      partially improved with levothyroxine treatment. Symptoms did not recur in the
      completely improved patients. CONCLUSION: Levothyroxine is an important and
      inexpensive treatment alternative in patients with CUA and TA.

PMID- 19753737
TI  - Dexpanthenol enhances skin barrier repair and reduces inflammation after sodium
      lauryl sulphate-induced irritation.
AB  - BACKGROUND: Dexpanthenol-containing creams have been widely used for treatment of
      lesions (superficial wounds) of the skin and mucous membranes. Dexpanthenol is
      converted in tissues to pantothenic acid, a component of coenzyme A. Coenzyme A
      catalyses early steps in the synthesis of fatty acids and sphingolipids which are
      of crucial importance for stratum corneum lipid bilayers and cell membrane
      integrity. AIM: In the present study, the effects were examined of a dexpanthenol
      containing cream on skin barrier repair, stratum corneum hydration, skin
      roughness, and inflammation after sodium lauryl sulphate (SLS)-induced
      irritation. METHODS: Irritation was induced by application of SLS in patch test
      chambers. The dexpanthenol-contaming cream or the vehicle were applied twice
      daily and barrier repair, hydration, roughness, and inflammation of the skin were
      determined by using biophysical methods. RESULTS: Significantly accelerated skin
      barrier repair was found in treatments with the dexpanthenol-containing cream
      (verum) compared with vehicle-treated (placebo) or untreated skin. Both verum and
      placebo showed an increase in stratum corneum hydration, but significantly more
      so with the dexpanthenol-containing cream. Both creams reduced skin roughness,
      but again the verum was superior. The dexpanthenol-containing cream significantly
      reduced skin redness as a sign of inflammation in contrast to the vehicle, which
      produced no effect. CONCLUSION: Treatment with a dexpanthenol-containing cream
      showed significantly enhanced skin barrier repair and stratum corneum hydration,
      while reducing skin roughness and inflammation.

PMID- 19753738
TI  - Time course of PUVA erythema.
AB  - Optimization of the PUVA regime requires knowledge of the time-course and dose
      response characteristics of PUVA erythema. Although existing guidelines recommend
      determination of the minimal phototoxic dose (MPD) 72 hours after UVA exposure
      and treatment administered 72 hours apart, recent evidence suggests that maximal
      PUVA erythema occurs beyond this time point, and hence the current assessment
      time underestimates the phototoxic effect of PUVA. This report reviews the
      current literature, including the authors' own experience of the characteristics
      of PUVA erythema, and recommends that the optimal time to read the PUVA MPD is 96
      h.

PMID- 19753739
TI  - Efficacy of three short-term regimens of itraconazole in the treatment of
      pityriasis versicolor.
AB  - BACKGROUND: Itraconazole is an oral antifungal agent, which has been proved to be
      effective in pityriasis versicolor. Different regimens for the treatment of
      pityriasis versicolor have been studied and good results were obtained with short
      term treatment regimens. OBJECTIVE: To compare the efficacy and tolerability of
      the classical regimen of 200 mg/day itraconazole for 5 days with the regimens of
      400 mg/day for 1 and 3 days. METHODS: A total of 60 patients with pityriasis
      versicolor were recruited into a randomized study. The patients were divided into
      three groups, each composed of 20 people. Mycological and clinical assessments
      were done before and on the 7th and 28th days after the treatment. Results were
      evaluated with the chi-squared test. RESULTS: The regimen of 400 mg/day
      itraconazole for 3 days was found to be as effective as the classical regimen of
      200 mg/day for 5 days in the treatment of pityriasis versicolor. The regimen of
      400 mg/day itraconazole for 1 day was found to be ineffective. CONCLUSION: This
      study has shown that a short course of itraconazole, 400 mg/day for 3 days,
      appears to be an effective and alternative treatment for pityriasis versicolor.

PMID- 19753740
TI  - Cutaneous endometriosis: a combination of medical and surgical treatment.
AB  - Cutaneous and subcutaneous endometriosis occurs most commonly as a secondary
      process in scars after abdominal or pelvic surgical procedures including
      hysterectomy, cesarean sections and episiotomy. Simple excision is the
      recommended management and local recurrence after adequate excision is uncommon.
      A 32-year-old woman presented with a 5-cm firm tumor on the right perineum. There
      was cyclical bleeding and fluctuation in size. She was initially treated with
      subcutaneous goserelin acetate. The lesion decreased in size and was then
      successfully excised 4 months later.

PMID- 19753741
TI  - Clinical and histologic changes determine optimal treatment regimens for
      microdermabrasion.
AB  - OBJECTIVE: To analyze the onset and extent of the dermatological changes
      associated with microdermabrasion. METHODS: Eleven volunteers, aged 31-62 years
      old, underwent a series of six aluminum oxide microdermabrasion facial treatments
      spaced over 7 to 10-day intervals. White light photography and digital
      ultraviolet fluorescent photography and skin biopsies were obtained prior to the
      study, after three treatments, and after six treatments. A 90-day no-treatment
      period ensured, after which biopsies and photographs were taken. RESULTS:
      Clinical improvements in dyschromia, actinic changes and fine rhytides were
      observed after six treatments. Compared with the controls, the treated areas
      demonstrated the following histological changes: epidermal thickening with basal
      cell hyperplasia and mitotic activity; flattening and widening of the rete pegs;
      papillary dermal thickening with deposition of collagen and elastic fibers; and
      perivascular inflammation in the dermis. After the no-treatment period some of
      the clinical and histologic changes persisted although they were less than those
      present immediately after the last treatment. Serial ultraviolet photography
      following microdermabrasion treatments revealed changes in the skin's
      pigmentation pattern that correlated clinically with improvements in dyschromia.
      CONCLUSION: Clinical and histological changes are most likely secondary to a
      mechanism resembling a reparative process. The persistent changes after a period
      of no-treatment suggests that some of the changes could be permanent. Clinicians
      can use this data to better determine the optimal interval frequency and
      treatment intervals with microdermabrasion.

PMID- 19753742
TI  - Primary cutaneous nocardiosis with multiple, subcutaneous abscesses in a patient
      with sarcoidosis.
AB  - A case of multiple subcutaneous nocardial abscesses is reported in a patient who
      received systemic corticosteroids over a period of about 4 years for the
      treatment of visceral sarcoidosis. The diagnosis of subcutaneous abscess caused
      by Nocardia asteroides was made based on bacteriological examination. It could
      not be determined before treatment whether the abscesses represented primary or
      secondary nocardiosis. Surgical drainage and systemic administration of
      minocycline hydrochloride dramatically resolved the cutaneous lesions. To the
      authors' knowledge, this is the first reported case in Japan of primary cutaneous
      nocardiosis in a patient with sarcoidosis.

PMID- 19753743
TI  - Fixed drug eruption due to tiaprofenic acid.
AB  - Tiaprofenic acid is a propionic acid derivative with analgesic, anti-inflammatory
      and antipyretic properties. Fixed drug eruption is a common cutaneous reaction by
      various drugs. Fixed drug eruption induced by tiaprofenic acid has not been
      reported previously. Described in this paper is a 57-year-old female patient with
      tiaprofenic acid-associated fixed drug eruption, which occurred shortly after
      starting tiaprofenic acid therapy for her osteoarthritis. Upon establishment of
      the diagnosis, tiaprofenic acid therapy was stopped and topical corticosteroids
      and systemic antihistamines were administered. The eruption resolved, leaving
      post-inflammatory hyperpigmentation within 5 days. The rash returned following
      tiaprofenic acid rechallenge. It is proposed that fixed drug eruption is a new
      side effect of tiaprofenic acid.

PMID- 19753744
TI  - Beware of hidden threats.

PMID- 19753745
TI  - Institutional policy on financial conflict of interest: objectivity in research.

PMID- 19753746
TI  - Minor surgery: how much is too much?

PMID- 19753747
TI  - Abdominal mass in a cynomolgus monkey (Macaca fascicularis). Granulosa cell
      tumor.

PMID- 19753748
TI  - When disaster strikes: rethinking caging materials.
AB  - The value of research using lab animals hinges on the ability to carry out
      experiments in a tightly controlled environment. Diet, caging materials (e.g.,
      cages and water bottles), and other environmental variables have the potential to
      create serious disruptions in animal studies. The authors describe the
      inadvertent damage of polycarbonate caging materials during the course of routine
      cagewashing, providing an instructive example and illustrating the importance of
      defined and controlled environmental conditions in biomedical research.

PMID- 19753749
TI  - Dressing for success: choosing garbing standards for the laboratory animal
      facility.
AB  - The animal research literature devotes much attention to the function of clothing
      and personal protective equipment in preventing transmission of zoonotic diseases
      from animal to human, but has said comparatively little about the potential for
      transmission of disease from human to animal. The authors consider appropriate
      garbing standards for personnel charged with various tasks within the animal
      facility, emphasizing the protection of animals from potential health threats.

PMID- 19753750
TI  - Security options for the laboratory animal facility.

PMID- 19753751
TI  - Endometriosis model development swine.
AB  - Despite the prevalence of endometriosis in the human population, there is a
      shortage of animal models for studying it. The authors describe the development
      of a swine model of endometriosis that allows researchers to evaluate
      laparoscopic techniques and instruments for diagnosing and treating the
      condition.

PMID- 19753752
TI  - Bringing evidence-based medicine to the bedside.

PMID- 19753753
TI  - Low Framingham risk score despite high prevalence of metabolic syndrome in
      asymptomatic North-Indian population.
AB  - BACKGROUND: Conflicting data exists regarding relationship between the Framingham
      risk score (FRS) and presence of metabolic syndrome (MS). Strong influence of age
      on FRS may further modify this relationship as prevalence of MS at younger age
      increases in South-Asian countries including India. However, only limited
      information is available about the prevalence of MS and its relationship with FRS
      in such populations at present. METHODS: Clinical examination and biochemical
      investigations were performed in 1905 asymptomatic office executives who
      underwent routine health check-up at a tertiary care centre in India during the
      year 2005. Diagnosis of MS and FRS were based on the modified National
      Cholesterol Education Program-Adult Treatment Panel III guidelines. RESULTS: Mean
      age of the subjects was 45.2 +/- 10.3 years and 71.8% were males. MS was present
      in 47.5% (905 of 1905) subjects. Overall, 76.8% patients with MS had 10-year
      cardiovascular (CV) risk < 10%, 20.6% had 10-20% risk and only 2.7% had > 20%
      risk according to FRS. In the lowest age-quartile, 95.9% patients had 10-year
      risk < 10%, 4.1% patients had 10-20% risk and none had > 20% risk. In contrast,
      in the highest age-quartile, less than half of the patients had 10-year risk <10%
      and nearly half had 10-20% risk of CV events. CONCLUSIONS: Although the
      prevalence of MS is markedly high in young asymptomatic Indians, majority have
      low 10-year risk of CV events as estimated by FRS. These findings necessitate
      continued emphasis on detection of MS in these populations as reliance on FRS
      alone may result in underestimation of CV risk in them.

PMID- 19753754
TI  - Multiple myeloma--presenting as acute kidney injury.
AB  - BACKGROUND: Multiple myeloma (MM) is a commonly encountered hematological
      malignancy with significant renal involvement and often presents as renal
      failure. The aim of the present study is to analyze clinical spectrum of acute
      renal failure (ARF) in patients with MM. MATERIAL AND METHODS: We analyzed 26
      (males 24; females 2) patients of multiple myeloma who were referred for
      evaluation of ARF between July 1994 - June 2007. The referral diagnosis did not
      include MM in majority 23 (88%) of the patients. Multiple myeloma was diagnosed
      by at least two of the four features; (1) lytic bone lesions, (2) serum or urine
      monoclonal peak, (3) Bence Jones proteinuria and (4) more than 20% plama cells in
      marrow aspirate. RESULTS: Multiple myeloma contributes 1.93% of total ARF cases
      (26/1342) over a period of thirteen years. Mean age of patients was 59.3 +/- 7.4
      years. The clinical manifestations of myeloma included; anemia (100%), Bence
      Jones proteinuria (80%), "M" peak in serum electrophoresis (69%), lytic bone
      lesions (62%), "M" peak in urine electrophoresis (54%), body pain (58%), plasma
      cells more than 20% in bone marrow aspirate (38%). Oliguric ARF was seen in 73%
      patients. The precipitating factors of ARF identified were; hypercalcemia (31%);
      infection (23%); volume depletion (19%); and NSAIDs in (15%). Dialysis support
      was needed in 77% of the patients because of severe renal failure at presentation
      with mean serum creatinine of 9.05 +/- 2.84 mg%. Seventeen patients completed
      chemotherapy, seven last to follow up and two patients died. Ten (38.5%) patients
      had complete recovery of renal function; three patients had partial recovery and
      off dialysis and four patients remained dialysis dependent. Remission of myeloma
      was achieved in nine of seventeen patients treated with chemotherapy Renal biopsy
      finding in nine patients revealed-cast nephropathy in (4), amyloidosis in (3),
      proliferative glomerulonephritis in (1) and cast nephropathy with chronic
      interstitial nephritis and plasma cell infiltration in one patient. CONCLUSION:
      Acute reversible renal failure is a common complication in MM, multiple myeloma
      should be considered as cause a cause of unexplained ARF in middle aged and
      elderly patients.

PMID- 19753755
TI  - Association of leukocyte count and hsCRP with metabolic abnormalities in subjects
      with normal glucose tolerance (CURES - 64).
AB  - OBJECTIVE: The aim of the present study was to assess the association of
      leukocyte count and high sensitivity C-Reactive protein (hsCRP) with metabolic
      abnormalities in subjects with normal glucose tolerance. METHODS: Subjects with
      Normal Glucose Tolerance (NGT) (n = 865) were recruited from the Chennai Urban
      Rural Epidemiology Study [CURES]. Standard methods were used for assessing hsCRP
      [Nephelometry, in a subset] and leukocytes [Flowcytometry, Sysmex SF-3000].
      Insulin resistance was calculated using the Homeostasis Assessment model (HOMA
      IR). RESULTS: Body mass index, waist circumference, systolic and diastolic blood
      pressure, fasting plasma glucose, HbA1c, serum cholesterol, LDL cholesterol, HOMA
      IR and hsCRP increased significantly with increasing tertiles of leukocyte count
      [p for trend < 0.001]. Both leukocyte count and hsCRP showed a positive
      correlation with cardiovascular risk factors. Leukocyte count showed a positive
      correlation with hsCRP [p = 0.008]. Both mean leukocyte count [p < 0.001] and
      hsCRP [p = 0.04] were higher in subjects with Metabolic Syndrome (MS), which
      increased with increase in number of metabolic abnormalities [p for trend <
      0.001]. Regression models showed leukocyte count [p < 0.001] and hsCRP [p = 0.03]
      to be associated with MS, even after adjusting for age and gender. CONCLUSION: A
      significant association exists between systemic inflammation [leukocyte count and
      hsCRP] and MS/cardiovascular risk factors in Asian Indians even among non
      diabetic subjects.

PMID- 19753756
TI  - Osteogenesis imperfecta.
AB  - BACKGROUND: Osteogenesis imperfecta (OI) is a rare metabolic bone disorder
      characterized by increased bone fragility, low bone mass, recurrent fractures and
      numerous extra-osseus features. Many patients remain undiagnosed and unattended
      particularly in developed countries. Presently, medical management with
      bisphosphonates has changed the scenario. MATERIALS AND METHODS: Twenty
      consecutive patients of OI were enrolled over a period of four years. Their
      clinical features, radiology, and biochemical parameters and treatment outcome
      were analysed. RESULTS: Of the 20 patients, 16 (80%) were male and 4 (20%) were
      female. Mean age (SD) of the patients was 20.8 (13.8) years. All the patients had
      presented with fractures, the number of fractures per person varying from 1 to
      20. Long bones were predominantly involved and thirteen (65%) had deformities of
      long bones. Ten (50%) had a positive family history of fractures after trivial
      traum. Eleven (55%) patients had dentiginous imperfecta (DI) and ten (50%) had
      blue sclerae at presentation. Impaired hearing was present in 1 patient only.
      Calcium profile was normal. Nine patients received pamidronate. Fracture
      frequency and pain decreased remarkably in these patients. CONCLUSION: Patients
      with OI presented late, predominantly with fracture of long bones, deformities
      and blue sclerae. Pamidronate therapy remarkably decreased fractures and pain in
      these patients.

PMID- 19753757
TI  - Scleroderma esophagus.

PMID- 19753758
TI  - Emphysematous pyelonephritis.

PMID- 19753759
TI  - Vitamin D status in India--its implications and remedial measures.
AB  - Vitamin D deficiency is epidemic in India despite of plenty of sunshine. The
      interpretation of vitamin D levels should be done with the solar zenith angle,
      minimal erythemal dose, skintype, UV Index and geographical location. All Indian
      studies uniformly point to low 25(OH)D levels in the populations studies despite
      abundant sunshine. All studies have uniformly documented low dietary calcium
      intake compared to Recommended Daily/Dietary Allowances (RDA) by Indian Council
      of Medical Research (ICMR). The vitamin D status of children is very low in both
      urban and rural population studied. Pregnant women and their new born had low
      vitamin D status. The effect of short course of loading doses of vitamin D
      doesn't have a lasting effect and a maintenance dose is needed. Low 25(OH)D
      levels has its implications of lower peak bone mass and lower BMD compared to
      west. There may be a public health need to fortify Indian foods with vitamin D.

PMID- 19753760
TI  - Albumin and lipid enriched albumin for the critically ill.
AB  - Albumin, the principal transporter of plasma fatty acids, binds to majority of
      the drugs ingested, traps oxygen radicals and has potent anti-oxidant actions.
      Albumin binds to its specific binding sites on vascular endothelial cells and
      thus, prevents endothelial apoptosis. Albumin regulates the enzyme pyruvate
      dehydrogenase, the flux of glucose and lactate in astrocytes, and enhances the
      formation of anti-inflammatory lipoxins, resolvins and protectins from
      docosahexaenoic acid (DHA) and other polyunsaturated fatty acids that, in turn,
      could limit ischemia-induced neuronal damage. This may explain the beneficial
      action of DHA-enriched albumin in stroke and other critical diseases.

PMID- 19753761
TI  - Epigenetics--gene silencing.
AB  - The discovery of the mechanism of RNA interference by ds RNA by Prof. Andrew Fire
      and Prof. Craig Mello in 1998, gave them the Nobel Prize in 2006. This discovery
      revealed a new mechanism for gene regulation through "gene silencing" at the
      transcriptional level (TGS) or at the post-transcriptional level (PTGS), which
      play a key role in many essential cellular processes. Today dsRNA is used as a
      powerful tool to experimentally elucidate the function of essentially any gene in
      a cell. The immense impact of the discovery of RNA interference (RNAi) on
      biomedical research and its novel medical applications in the future are reviewed
      in this article, with particular stress on therapeutic applications of radio
      labeled antisense oligonucleotides (RASONs) for diagnosis and treatment of
      various cancers and neurodegenerative diseases by "gene silencing". Antisense
      oligonucleotides (ASONs) can also modulate alternative splicing which 74% of all
      human genes undergo. The most effective targeting strategy employs simultaneous
      blocking SnRNP binding sites and splice junctions. Correction of splicing by
      ASONs can be used to silence mutations causing aberrant splicing as in
      thalassemia, Duchenne muscular dystrophy and cystic fibrosis.

PMID- 19753762
TI  - Bilateral anterior cerebral artery infarction following viper bite.
AB  - The viper is one of India's most commonly encountered poisonous snakes and
      envenomation following viper bite usually leads to consumption coagulopathy.
      Clinical manifestations most frequently include external and internal bleeding.
      In the setting of viper envenomation, large-vessel thrombosis is a very rare
      occurrence. Also, bilateral anterior cerebral artery infarction, when unrelated
      to anatomical abnormalities, subarachnoid haemorrhage, surgery or trauma, itself
      is an exceedingly rare event. We report a case of a 24-year-old previously
      healthy man who presented with bilateral anterior cerebral artery infarction
      following a viper bite. We also present hypotheses that may explain this unusual
      occurrence.

PMID- 19753763
TI  - Isoniazid toxicity presenting as status epilepticus and severe metabolic
      acidosis.
AB  - Isoniazid (INH) is an integral component of treatment of tuberculosis. An acute
      overdose is potentially fatal and is characterized by the clinical triad of
      repetitive seizures unresponsive to the usual anticonvulsants, metabolic acidosis
      with a high anion gap and coma. The diagnosis of INH overdose should be
      considered in any patient who presents to emergency medical services (EMS) with
      the triad. We report a patient presenting with multiple generalised tonic clonic
      (GTC) convulsions with severe metabolic acidosis as a manifestation of INH
      toxicity.

PMID- 19753764
TI  - Multifocal idiopathic fibrosclerosis mimicking tuberculosis of the abdomen.
AB  - We present a 13 year old girl from Assam who had been treated as abdominal
      tuberculosis for 2 years due to the presence of refractory lymphocyte-predominant
      ascites and multiple small bowel strictures associated with significant anorexia
      and weight loss. On evaluation she was found to have retroperitoneal fibrosis
      with hydroureteronephrosis, mediastinal fibrosis and a retro-orbital
      pseudotumour. Based on these findings the diagnosis of Multifocal Idiopathic
      Fibrosclerosis (MIFS) was made. Ascites and multiple bowel strictures have been
      only rarely been described in association with MIFS. The other unique features in
      this patient were the early age of presentation, the presence of mediastinal
      fibrosis in association with retroperitoneal fibrosis, extensive soft tissue
      fibrosis of the neck, axillae and the presence of trismus. In a country like ours
      where Tuberculosis is commonplace, one would not think twice about treating such
      a case with antituberculous therapy. However, with a constellation of findings
      suggestive of a diffuse fibrotic process, MIFS should be an important
      consideration.

PMID- 19753765
TI  - Gastrointestinal histoplasmosis mimicking abdominal tuberculosis.
AB  - We report an elderly male who presented with history of chronic diarrhoea. The
      patient underwent colonoscopy and CT scan of the abdomen which strongly suggested
      tuberculosis; however histopathology showed presence of budding forms of
      Histoplasma capsulatum. The patient was started on oral itraconazole on which he
      improved remarkably.

PMID- 19753766
TI  - Paraneoplastic palmar fasciitis and polyarthritis syndrome.
AB  - Palmar fasciitis and polyarthritis syndrome is a rare paraneoplastic syndrome
      that has been reported mainly for ovarian cancers. It is thought to be a tumour
      associated autoimmune disorder. It is associated with polyarthritis and rapid
      flexion contractures of hands with palmar nodules due to palmar fasciitis.
      Similar paraneoplastic features in gastric cancers have seldom been reported.
      Here, I am reporting a case of paraneoplastic syndrome of metastatic gastric
      adenocarcinoma with polyarthritis of hands and contractures of multiple joints
      with asymmetric clubbing (right hand more than left hand) and hyperpigmentation
      over back of hands and fingers. Hyperpigmentation and asymmetric clubbing have
      not been reported in literature in palmar fasciitis and polyarthritis syndrome.

PMID- 19753767
TI  - Medical philately (medical theme on stamps). Alzheimer's disease.

PMID- 19753768
TI  - Headache as the sole presenting symptom of acute myocardial infarction.

PMID- 19753769
TI  - Unusual presentation of bronchogenic carcinoma.

PMID- 19753770
TI  - Managing non-communicable diseases at a secondary level hospital.

PMID- 19753771
TI  - Should dying prisoners be given their freedom for a more dignified end?

PMID- 19753772
TI  - The nut crackers.
AB  - Peanut allergy can be life-threatening, but a new treatment shows promise.

PMID- 19753773
TI  - A gift of hope to people with HIV.
AB  - South Africa has more people with HIV than any other country in the world. While
      antiretrovirals are free, there are other treatment costs.

PMID- 19753774
TI  - Life worth living.
AB  - Older people, especially those with long-term conditions, can become socially
      isolated. One trust has tackled the problem using volunteers.

PMID- 19753775
TI  - Rocky road to recovery.

PMID- 19753776
TI  - Identifying and assessing anxiety in pre-operative patients.
AB  - Increasing demands for hospitals to be more efficient mean that patients
      attending for an operation are generally admitted on the day of surgery. As a
      result, healthcare professionals have little time to talk to the patient to
      ascertain his or her wellbeing, to check for any signs of anxiety and ask whether
      the patient requires further information about the forthcoming procedure.
      Healthcare professionals should be encouraged to use appropriate interventions to
      identify and assess anxious patients. There are several instruments available to
      measure the patient's level of pre-operative anxiety. This article reviews the
      Amsterdam Preoperative Anxiety and Information Scale, which is easy for patients
      to complete and may help to identify which individuals need extra support.

PMID- 19753777
TI  - Improving standards of care for patients: a pilot project.
AB  - This article demonstrates how one of England's largest primary care trusts
      developed, piloted and evaluated a quality improvement tool--the quality
      framework--to support the implementation of clinical governance at a team level.
      This article shares good practice and key learning points from this experience.

PMID- 19753778
TI  - Orthopaedic plaster casting: nurse and patient education.
AB  - Orthopaedic casts are used in the management of fractures and to support and
      correct deformities. The application and removal of plaster casts is a skill
      requiring knowledge, judgement and sensitivity. Nurses need to have a good
      working knowledge of the main principles of plaster casting to ensure safety and
      provide patients with appropriate advice and information about how to care for
      casts and how to recognise possible complications.

PMID- 19753779
TI  - Intravenous therapy.

PMID- 19753780
TI  - Power to the patient.

PMID- 19753782
TI  - Opportunity knocks.

PMID- 19753781
TI  - Teaching carers the tricks of the trade.

PMID- 19753783
TI  - Who coined POCT?

PMID- 19753784
TI  - Hemoglobinopathies and clinical laboratory testing.

PMID- 19753785
TI  - Acute-care testing at the point of care: now and in the future.

PMID- 19753786
TI  - Lab software: the global scene.

PMID- 19753787
TI  - Law provides for time off work.

PMID- 19753788
TI  - Be prepared for inspections.

PMID- 19753789
TI  - H1N1 warns of public-health deficiencies.

PMID- 19753790
TI  - Accessibilty and cost constraints: factors impeding the development of reasonable
      access to publicly insured health services in Canada (Saskatchewan).

PMID- 19753791
TI  - Managing risk around influenza A (H1N1) (swine flu)--what employers should know.

PMID- 19753792
TI  - Natural Health Products Directorate releases new policy on the interface of food
      and natural health products.

PMID- 19753793
TI  - Role of live yeasts in rumen ecosystem.
AB  - For many years, ruminant nutritionists and microbiologists have been interested
      in manipulating the microbial ecosystem of the rumen to improve production
      efficiency by domestic ruminants. Antibiotic ionophores have been used
      successfully for this purpose. However, the use of antibiotics in animal feeds
      has been banned in the European Union since January 2006 due to the risk of
      spreading antibiotic resistance. For this reason, scientists have become
      interested in evaluating other alternatives to control specific microbial
      populations to modulate rumen fermentation. Dietary supplements of live yeast
      preparations, based on Saccharomyces cerevisiae, have been reported to improve
      health and productivity of ruminants. In contrast to antimicrobial agents, live
      yeasts offer a natural alternative to manipulate animal performance. This review
      discusses the modes of action of live yeasts in rumen ecosystem and their
      subsequent effects on animal performance.

PMID- 19753794
TI  - [Examination of the compatibility of a Salmonella Typhimurium-live vaccine
      Salmoporc for three day old suckling piglets].
AB  - The present study intended to investigate the compatibility of the orally
      applicated Salmonella Typhimurium live vaccine Salmoporc on day 3 and 21,
      respectively. Piglets which only received saline solution orally were used as
      negative control. During eight hours following vaccination, fecal consistency,
      body temperature as well as body condition were evaluated. Furthermore, in
      addition to the daily measures of body temperature and body condition, weekly
      weight controls as well as bacteriological examination referring to the duration
      of excretion of the vaccine strain, were carried out until the end of the study.
      Additionally, distribution and persistence of the pathogen in different tissues
      were examined. Using serological determination of salmonella antibodies, immune
      response was scrutinised. Oral vaccination resulted in a significant rise of the
      body temperature.The vaccine strain could be isolated from fecal samples until
      the 28th day (seven days after the second vaccination). The vaccination strain
      persisted until six weeks after the second vaccination in organs of the piglets,
      whereas the last detection was from samples of small and large intestine. Field
      strains could neither be isolated from fecal nor from organ samples of vaccinated
      and control group. Until the end of the study, control animals were negative by
      bacteriological examination of fecal and organic samples. Seroconversion was
      observed from day seven after the second vaccination. Mean concentration of
      antibodies was significantly higher in vaccinated than in control animals three
      weeks after vaccination.

PMID- 19753795
TI  - Mouse intestine colonization ability of Campylobacter coli strains.
AB  - Campylobacter coli is an etiological agent of gastrointestinal and
      extraintestinal infections in man and animals, and can be found as a commensal in
      gastrointestinal tract of animals. In this study, we aimed to determine
      differences among C coli strains in colonization of the intestinal tract of mice.
      Seven C coli strains isolated from diarrheic patients, asymptomatic hosts and
      chicken carcasses were used for this study. Each strain was inoculated with 0.1
      ml of a bacterial suspension (3 x 10(8) CFU/ml) to 5 weanling mice,
      intragastrically. For the isolation of C coli, faecal pellets collected before
      inoculation and after inoculation at particular intervals were cultured on
      Campylobacter Selective Agar. Seven C. coli strains were divided into 3
      colonization groups, based on faecal shedding. Group I showed immediate
      colonization, with prolonged excretion of organism in all mice. Group II showed
      delayed and short time colonization of C. coli. Group III could not colonize
      mice. Division of isolates into colonization groups was as follows: Group I
      included 3 strains from gastrointestinal disease; Group II included 2 strains
      from asymptomatic hosts and Group III included 2 strains from chicken carcasses.
      The study showed that there were marked differences among C coli strains with
      respect to their colonization potential and it may depend upon the origin of the
      strain. For understanding the complete pathogenesis of Campylobacter spp., a
      greater number of strains from different sources and geographical locations
      require to be tested in further investigations in the light of our findings.

PMID- 19753796
TI  - Influence of ram presence (permanent vs. intermittent) on estrus parameters and
      behaviours in Kivircik ewes.
AB  - The present study was undertaken to investigate the effects of type of ram
      presence (permanent vs. intermittent) on estrus onset, estrus duration and
      frequency of sexual behaviours in Kivircik ewes. During the breeding season, 20
      multiparous Kivircik ewes were divided into two groups of permanent (PR) and
      intermittent (IR) presence of ram. Estrus was synchronized with fluorgestone
      acetate intravaginal sponges left for 14 days, plus an injection of 600 IU PMSG
      at the time of sponge removal. PR ewes introduced with ram immediately after
      sponge removal and remained with the ram throughout the study (5 days). IR ewes
      were exposed to ram twice a day, only during the observation periods. Behavioural
      observations were performed twice a day (at 07:00 a. m. and 07:00 p.m.) for a 2
      hour period. Estrus onset was 32.40 +/- 1.60 h for PR group and 27.60 +/- 2.40 h
      for IR group (p > 0.05). Estrus duration was 15.60 +/- 1.83 h and 34.80 +/- 2.15
      h for the same groups, respectively (p < 0.001). Standing was the most frequently
      displayed behaviour in both groups. IR ewes displayed sexual (p < 0.001), eating
      (p < 0.001), standing (p < 0.001), walking (p < 0.001), urination (p < 0.001) and
      defecation (p < 0.05) behaviours much more than the PR ewes. Frequency of each
      sexual behaviour was higher in IR group compared with PR group throughout the
      study. Among the proceptive behaviours investigated, head-turning was the most
      frequently displayed behaviour in both groups. Soliciting, non-firm standing,
      sniffing scrotum and anogenital sniffing behaviours were also expressed by the
      ewes considerably. It is concluded that, if the ewes are exposed to ram
      intermittently, behavioural signs of estrus could be recognized more
      successfully. Furthermore, the possibility of insemination of estrous ewes
      becomes much higher by the intermittent presence of ram and thus reproductive
      performance of the herd could be improved.

PMID- 19753797
TI  - Evaluation of estrogen receptor and circulating estradiol levels in pre- and
      postmenopausal women with periodontal disease.
AB  - Although the presence of estrogen receptors (ERs) in the gingival tissues has
      been confirmed, there is as yet insufficient literature regarding its expression
      in periodontal health and disease. Gingival samples were collected from 40
      subjects who were divided into four groups. (Group A, premenopausal health; Group
      B, premenopausal periodontitis; Group C, postmenopausal health; Group D,
      postmenopausal periodontitis). ERs were identified with an anti-ER monoclonal
      antibody (Bio Genex). Circulating estradiol (E2) levels were estimated using the
      Genix E2 EIA commercial kit. An inverse relationship between E2 and ER levels in
      gingiva was observed in all the samples. There was significantly reduced
      expression of ERs in the gingiva of subjects with chronic periodontitis when
      compared to those with healthy periodontium in the postmenopausal group.

PMID- 19753798
TI  - Treatment of human infrabony periodontal defects by grafting human cultured
      periosteum sheets combined with platelet-rich plasma and porous hydroxyapatite
      granules: case series.
AB  - In a previous publication from our research group we reported that a combination
      of platelet-rich plasma (PRP) and hydroxyapatite (HA) granules resulted in a
      significantly favorable clinical result in treating osseous defects. The aim of
      this study is to evaluate the clinical response of human cultured periosteum
      (HCP) sheets in combination with autologous PRP and HA granules used as a tissue
      engineered grafting material for the treatment of infrabony defects in three
      female patients. Periosteum cell specimens were harvested from the mandible of
      each patient and cultured for six weeks until HCP sheets were formed. The
      periodontal surgery fully exposed the osseous defects and debridement and root
      planing were carried out. The coagulated PRP and HA mixture were placed into the
      osseous defects, and then they were covered with autologous HCP sheets. Six
      months post-surgery there were gains in clinical attachment and radiographic
      evidence of infrabony osseous fill. It may be concluded that HCP sheets combined
      with PRP and HA granules showed significant promise for treating human
      periodontal infrabony defects. A factor contributing to these favorable clinical
      results would be the presence of osteogenic cells in the HCP sheets, which
      provided greater regeneration potential.

PMID- 19753799
TI  - Hemisection of teeth with questionable prognosis. Report of a case with seven
      year results.
AB  - This case reports the long-term effects of hemisection of teeth with questionable
      prognosis. The outcome in a 34-year-old male patient with mobile teeth in the
      lower left posterior sextant is reported. Removal of the mesial root of the
      mandibular first molar and the distal root of the mandibular second molar was
      done. The final restoration was performed after using a provisional restoration
      for three months. The final restoration functioned well without detectable
      mobility or any noticeable bone loss for up to seven years. Within the limits of
      this report, the hemisection of molars with questionable prognosis can maintain
      the teeth without detectable bone loss for a long-term period, provided that the
      patient has optimal oral hygiene.

PMID- 19753800
TI  - Polymorphism of salivary histatin gene and periodontal disease in the Japanese
      population.
AB  - Chronic periodontitis is a widespread and major dental disease. Recent studies
      have analyzed a possible relationship between polymorphism of several genes and
      periodontitis. Histatins are salivary polypeptides with fungicidal activities
      against Candida albicans and yeast and bactericidal activities against
      Porphyromonas gingivalis and Streptococcus mutans. Histatins are part of the
      innate defense of the oral cavity. We examined the frequency of the polymorphism
      codon 23 of the histatin 3 gene (HIS2 allele) in relation to periodontitis in the
      Japanese population. The subjects were 143 Japanese individuals, of which 63 were
      healthy control subjects and 80 were periodontal patients. We isolated genomic
      DNA from lingual mucosal cells and tested them for single nucleotide polymorphism
      (SNP) by polymerase chain reaction-restriction fragment length polymorphism (PCR
      RFLP). The incidence of polymorphism was analyzed statistically by Fisher's exact
      test. The results indicated that the gene polymorphism at codon 23 of the
      histatin 3 gene was not associated with periodontitis in the Japanese population
      (p = 0.166). Rather, if at all, it appeared to be associated with resistance to
      periodontitis.

PMID- 19753801
TI  - Guided tissue regeneration membranes for periodontal regeneration--a literature
      review.
AB  - Guided tissue regeneration materials were reviewed in this paper and can be
      categorized as non-resorbable and bioabsorbable. Both materials have been used
      extensively in periodontal regeneration with no difference in the clinical
      outcome. Selection of barrier material depends on resorbability, size of the
      defect, morphology of the defect, operator preference and patient acceptance.

PMID- 19753802
TI  - Interview with a quality leader: Joel T. Allison on healthcare technology and
      quality care. Interview by Marie St. Rose.
AB  - Managing the delivery of healthcare in a turbulent environment is challenging. In
      this article, Joel T. Allison shares his knowledge, experiences, and best
      practices on healthcare technology and quality care.

PMID- 19753803
TI  - Successes and lessons learned implementing the sepsis bundle.
AB  - Sepsis is well described in the literature as a leading cause of possibly
      preventable death in the United States. Analysis of baseline data indicated
      capacity to reduce mortality, significant variation in clinical practice patterns
      and opportunities for reducing cost per case. Following an enterprise-wide
      challenge to save lives, a multidisciplinary, facility-based team was organized
      to improve sepsis care. Systematic improvements in recognizing sepsis and
      standardizing care resulted in a dramatic reduction in mortality and a
      significant reduction in direct variable cost.

PMID- 19753804
TI  - Coronary artery bypass graft surgery: surgical site infection prevention.
AB  - This project raised awareness of various factors influencing the risk of
      developing deep sternal wound infection, postoperative cerebravascular accident,
      and adverse cardiac events. It elevated attention to evidence-based research and
      improved outcomes relating to parameters of surgical antibiotic prophylaxis on
      risks of surgical site infection (SSI) following coronary artery bypass graft
      (CABG) surgery. Analysis of patient outcomes revealed CABG improvements were
      statistically significant and showed improvement after implementing improvement
      strategies. The project suggests improvement projects in hospitals to prevent
      CABG SSI should focus on a team approach and incorporate evidence-based practices
      as effective interventions and solutions.

PMID- 19753805
TI  - The rapid assessment of hospital procurement barriers in donation: assessing
      hospitals for change.
AB  - Assessment of the hospital environment is integral to improving the organ
      donation process in healthcare organizations. This paper introduces a novel
      approach to the assessment and improvement of donation processes: the Rapid
      Assessment of hospital Procurement barriers in Donation (RAPiD). The RAPiD is a
      qualitative needs assessment tool for identifying barriers to donor
      identification and referral, and family requests for donation. Improving the
      donation process has become a national priority and can potentially save or
      improve the lives of thousands of Americans each year. The RAPID yields a rich
      description of the hospital environment that is readily translated into action
      oriented recommendations for change.

PMID- 19753806
TI  - Sedation reduction in a pediatric radiology department.
AB  - An initiative by the Children's Hospital of Pittsburgh radiology department to
      reduce sedations of pediatric patients undergoing computerized tomography
      scanning has resulted in a significant decline in sedation rates, reduced rates
      of sedation-related complications, a significant productivity gain as a result of
      increased procedural volume, improved patient and family satisfaction, and no
      diminution of image quality. The techniques used to implement this initiative are
      applicable in any healthcare setting in which pediatric patients are routinely
      sedated for medical procedures.

PMID- 19753807
TI  - Credentialing ambulatory physicians based upon core competencies.
AB  - Economic forces have created a revolution in health care. Traditional models of
      practice are changing. The care of the patient is being split between the
      hospitalist and the primary care physician in the ambulatory setting.
      Increasingly there are physicians that no longer come to the hospital except to
      attend meetings, yet departmental chairpersons must credential and privilege
      these physicians and vouch for their competence. This article discusses ways to
      be able to credential and privilege ambulatory physicians or physicians that
      rarely see patients in the hospital (low volume admitters) by using the core
      competencies designed by ACGME that are currently used to evaluate residents.

PMID- 19753808
TI  - Improving colonoscopy referral rates through computer-supported, primary care
      practice redesign.
AB  - This quality improvement project was designed to improve rates of referral for
      colonoscopy screening in the Utah Health Research Network, University of Utah
      Community Clinics. This study was conducted between October 2004 and June 2007
      with the main intervention being a clinic workflow modification using
      computerized screening reminders embedded in the electronic medical record (EMR).
      The intervention led to sustained improvement, largely driven by the performance
      of two network clinics. This study demonstrates that a robust EMR, with decision
      prompts, accompanied by clinic workflow changes and feedback to providers, can
      lead to sustained change in the rates of colonoscopy referral.

PMID- 19753809
TI  - Assisted living checklists for consumers.
AB  - In order for consumers to compare long-term care facilities, information about
      those facilities must be readily available. It is unclear how much information is
      available for assisted living facilities (ALFs). In this investigation, an
      internet search was performed to determine what information is available in each
      state. It was found that most states have a number of descriptive indicators. The
      way in which the information is displayed varies substantially among different
      states, as well as the detail and depth of information. While a variety of useful
      information was found, it was not necessarily found easily. It is important to
      enable consumers to make a direct comparison between ALFs, and in order to do
      that there needs to be obvious standardization of presented information among the
      different states.

PMID- 19753810
TI  - The challenges ahead.

PMID- 19753811
TI  - Geriatrics and dentistry.

PMID- 19753812
TI  - Informed consent and the cognitively impaired geriatric dental patient.
AB  - Many geriatric patients will have cognitive impairment, sometimes temporary and
      other times progressive. Dentists are challenged to evaluate for the presence of
      cognitive impairment that can affect the consent process. This review gives an
      overview of types of cognitive impairments, clues to recognizing these
      conditions, how they affect the dental consent process, and what makes an
      effective informed consent. When there is doubt of a patient's capacity to
      consent, prudence calls for stopping dental treatment and referring the patient
      for a medical evaluation.

PMID- 19753813
TI  - Diagnosing oral lesions in older adults--a systematic approach.

PMID- 19753814
TI  - An approach to assessing elder abuse and neglect in the dental office.
AB  - Elder abuse and neglect is a complex phenomenon with no clear markers identified
      as both reliable and valid in the dental operatory. Applying the concepts and
      definition of abuse and attention to risk factors for abuse could lead the
      clinician, as the head of the care team to situations where abuse of an elder
      could be suspected. Once abuse is suspected, direct questioning and comprehensive
      assessment of an elders' physical, emotional, and emotional state could be
      recorded as part of social history in their dental records. A multidisciplinary
      team approach is encouraged to combat elder abuse. In Texas, state statutes on
      suspected abuse mandate reporting to appropriate Adult Protective Services within
      your region with stipulated penalties for failure to report suspected abuse or
      neglect. Elder abuse hotlines are (800) 252-5400 or (512) 834-3784 (elder abuse
      domestic or community).

PMID- 19753815
TI  - Bisphosphonate medications--the good, the bad, and the ugly.

PMID- 19753816
TI  - Dental management of patients taking antiplatelet medications.
AB  - Antiplatelet medications are drugs which decrease platelet aggregation and
      inhibit thrombus (clot) formation. They are widely used in primary and secondary
      prevention of thrombotic cerebrovascular or cardiovascular disease. The most
      common antiplatelet medications are the cyclooxygenase inhibitors (aspirin) and
      the adenosine disphosphate (ADP) receptor inhibitors clopidogrel (Plavix) and
      ticlopidine (Ticlid). The dental management of patients taking these drugs is
      reviewed here.

PMID- 19753817
TI  - Copy that!

PMID- 19753818
TI  - Oral and maxillofacial pathology case of the month. Scleroderma.

PMID- 19753819
TI  - The Texas long-term care partnership: good news ahead.

PMID- 19753820
TI  - CDC changes recommendation for babies born to mothers with Streptococcus
      agalactiae.

PMID- 19753821
TI  - Obstacles that stand in the way of partnering with patients.

PMID- 19753822
TI  - Mentoring a primary care resident: an example of reflective learning.

PMID- 19753823
TI  - Effects of gender, alcohol, smoking, and dairy consumption on bone mass in
      Wisconsin adolescents.
AB  - INTRODUCTION: Failure to attain peak bone mass during adolescence may be an
      important contributor to the development of osteoporosis. METHODS: This
      prospective, descriptive study evaluated the relationship between osteoporosis
      risk factors and attainment of bone mass in 239 Wisconsin high school students.
      Students completed an annual risk assessment questionnaire that included
      questions about dairy intake, alcohol use, and smoking. Heel bone mineral density
      (BMD) was measured in the 9th grade (year 1) and 12th grade (year 4). RESULTS: A
      total of 109 students were included in the final analysis of a covariance model
      used to predict year 4 BMD. The model included separate year 1 BMD slope and
      intercept terms for males and females and indicator variables for adequate dairy
      intake and combined alcohol habits or smoking habits (overall P<0.001, multiple
      r2=0.871). The predicted year 4 BMD for females was 0.07 g/cm2 plus 85.6% of
      their year 1 BMD. For males, predicted year 4 BMD was 0.008 g/cm2 plus 110% of
      their year 1 BMD. Self-reported dairy intake of > or = 4 servings per day was
      associated with a 0.032 g/cm2 increase in BMD, while self-reported smoking or
      alcohol use was associated with a decrease in BMD of 0.028 g/cm2. CONCLUSIONS:
      Alcohol or smoking had a significant negative effect on bone density, whereas
      adequate dairy intake (>4 servings per day) had a favorable effect in Wisconsin
      adolescents. Sex differences in bone density growth were clearly identified, with
      males tending to gain BMD and females tending to lose BMD by year 4.

PMID- 19753824
TI  - Cardiovascular risk profile: comparison between white and Southeast Asian youth
      in Wausau SCHOOL Project.
AB  - INTRODUCTION: The Wausau School Children Have Early Onset Of Leading Risk Factors
      of Cardiovascular Disease and Diabetes Mellitus (SCHOOL) Project is a community
      based effort to assess the cardiovascular (CV) health of students in the Wausau
      School District (WSD). It has been previously demonstrated that risk factors for
      CV disease are prevalent and increase with age. Wausau is also a major relocation
      center for Southeast Asian (SEA) immigrants. Few data are available on the CV
      health of SEA immigrants. This investigation compares the relative frequency of
      CV risk factors in SEA and white students in the WSD. METHODS: A random selection
      of 2nd, 5th, 8th, and 11th grade students provided demographic data, health
      history, sex-adjusted body mass index (BMI), fasting glucose levels, blood
      pressure levels, and nuclear magnetic resonance lipid profiles (Liposcience).
      This included 519 white and 48 SEA students. To assess for CV disease risk
      factors, study participants were examined for dyslipidemia, hypertension,
      impaired fasting glucose levels, above-normal body weight, and history of
      smoking. RESULTS: Risk factors for CV disease increased with age for both white
      and SEA participants. The mean number of risk factors in SEA participants was
      1.63 compared to 1.12 for white participants (P=0.016). The mean number of risk
      factors also increased significantly across grade levels (P=0.001). There was no
      difference in mean BMI values (P=0.58). No significant differences were found in
      triglycerides, total cholesterol, LDL cholesterol, HDL cholesterol, blood
      pressure, or glucose values. Dyslipidemia was present in 53% of SEA students and
      42% of white students (P=0.14). CONCLUSION: CV risk factors are common in school
      age children, and the number of risk factors increases with age. SEA students
      presented a greater prevalence of CV risk factors than white students, but were
      not significantly more overweight. Interestingly, in a relatively short time
      period after immigration, first-generation SEA youth have developed a number of
      CV risk factors equal to or greater than those of their white counterparts.

PMID- 19753825
TI  - Prevalence of carpal tunnel syndrome in pregnant women.
AB  - Carpal tunnel syndrome (CTS) is a frequent complication of pregnancy, with a
      prevalence reported as high as 62%. The most typical symptoms are numbness and
      tingling in the thumb, index finger, middle finger, and radial half of the ring
      finger. Other common manifestations include burning dysesthetic wrist pain, as
      well as the loss of grip strength and dexterity. Proximal radiation along the
      volar forearm, medial arm, and shoulder, while not as common, is not unusual.
      Symptoms are often worse at night and can be exacerbated by forceful activity and
      extreme wrist positions. It can be diagnosed to a high degree of specificity via
      history and physical examination. Median nerve function is impaired in virtually
      all pregnant women during the third trimester, even in the absence of symptoms.
      Treatment is symptomatic and usually consists of activity modification,
      splinting, edema control, and, if necessary, steroid injections. While most women
      experience symptomatic improvement following delivery, a significant percentage
      may still have some complaints up to at least 3 years post-partum and continue to
      wear splints. A high level of vigilance should be maintained in the management of
      these patients.

PMID- 19753826
TI  - Arrow trauma to cervical spine.
AB  - A 50-year-old man was the victim of an accidental arrow shooting while hunting.
      The arrow entered his posterolateral neck and came to rest in the space between
      the C1/C2 vertebrae in his cervical spine. He was able to maintain his own
      cervical immobilization. His hunting partners drove him to meet emergency medical
      technicians, who stabilized the arrow shaft, transferred him to a backboard and
      gurney, and continued manual cervical immobilization en route to a local
      hospital. Cervical spine X-ray results compelled an air ambulance transfer to a
      trauma center where he underwent surgical intervention to remove the arrow.
      Following approximately 12 months of physical and occupational therapy, he
      returned to work full-time. Adherence to training and utilization of proven
      techniques involving pre-hospital transfers and positioning of cervically injured
      patients proved imperative to the patient's ultimate recovery.

PMID- 19753827
TI  - A case of synchronous unilateral parotid tumors of different histologic types.
AB  - A case of unilateral synchronous tumors of the parotid gland in a 71-year-old man
      is presented. The clinical, radiographic, and histologic features are discussed
      along with a review of the literature.

PMID- 19753828
TI  - Brief report: Measuring the attitudes of health care professionals in Dane County
      toward adolescent immunization with HPV vaccine.
AB  - OBJECTIVE: Evaluate regional health care professionals' views of human
      papillomavirus (HPV) vaccination recommendations for adolescent patients through
      a mailed survey. METHODS: A 16-question self-administered questionnaire was
      mailed to 518 physicians, physician assistants, and nurse practitioners in Dane
      County, Wis, working in family medicine, pediatrics, or gynecology in September
      2006. The survey addressed health care professionals' willingness to recommend
      the HPV vaccine, populations they would target for a recommendation, and
      justifications provided to patients regarding the benefits of HPV vaccination.
      RESULTS: Of the health care professionals who were mailed a survey, 39%
      responsed. The majority (95%) of professionals were willing to recommend the HPV
      vaccine to their adolescent patients. Most practitioners (67%) were planning to
      recommend the vaccine to their female patients only and are most comfortable
      vaccinating patients >10 years of age. Health care professionals were looking to
      their own health profession organizations for vaccination recommendations.
      CONCLUSION: Health care professionals in family medicine, pediatrics, and
      gynecology in Dane County, Wis, have positive attitudes regarding HPV vaccine
      recommendation for their adolescent patients.

PMID- 19753829
TI  - MCW is regional home to comprehensive trauma programs.

PMID- 19753830
TI  - Tips for entering into 'meaningful' EHR contracts with vendors.

PMID- 19753831
TI  - Changes coming in regulation of medical profession.

PMID- 19753832
TI  - [Malformations and congenital anomalies: impact and future].

PMID- 19753833
TI  - [Mucosal complication of cutaneous leishmaniasis].
AB  - A 74-year-old man from the rural area of Caicedonia, Valle del Cauca Province,
      was diagnosed with uncontrolled hypertension, stage IV chronic renal failure and
      severe anemia. Fifteen years earlier, while living in Guaviare Province, he was
      diagnosed with leishmaniasis-with lesions located on the right upper and lower
      eyelids, left auricle and limbs. At that time, he received an incomplete
      treatment with antimonials. The patient had experienced 8 years of progressive
      mucosal lesions located in the upper lip, nasal mucosa and right upper and lower
      eyelids (figure 1). A histopathological diagnosis of leishmaniasis was made and
      confirmed by polymerase chain reaction (figure 2). Treatment with antimonials
      (Glucantime) was contraindicated due to the patient's comorbidities. Inpatient
      supervised treatment with miltefosine (Impavido 50 mg capsules) was initiated
      according to the national guidelines of 1.8 mg/kg/day for 28 days. Clinical
      follow up and routine laboratory tests (creatinine, BUN, liver function tests and
      complete blood counts) were done during and after treatment; no complications
      were reported. Medical follow up was continued until the Internal medicine,
      ophthalmology, and plastic surgery consultations were provided for subsequent
      management of the pathology. Mucocutaneous leishmaniasis is a serious preventable
      complication of cutaneous leishmaniasis. This case illustrated a failure in
      opportune diagnosis and treatment of this disease as a consequence of an
      inadequate leishmaniasis control program. The case indicated the effectiveness of
      miltefosine as a therapeutic option in patients for whom antimonial treatment is
      contraindicated.

PMID- 19753834
TI  - [Cutaneous myiasis by Cochliomyia hominivorax (Coquerel) (Diptera Calliphoridae)
      in Hospital Universidad del Norte, Soledad, Atlantico].
AB  - Human myiasis is the parasitism of human tissues by fly larvae. Diagnoses are
      based on clinical pattern of tissue damage and presence of insect stages. Herein,
      a case myiasis is described in a seven-year-old female child. She presented with
      fever associated with abscessed scalp lesions containing exposed larvae. Severe
      pediculosis was also observed. The patient was hospitalized and treated with
      clindamycin, gentamicin (for bacterial secondary infections) and ivermectin
      (treatment for lice) after which the patient showed clinical improvement and was
      discharged four days later. Since human myiasis can be caused by a number of
      different species, larvae were collected from the patient and identified as those
      of Cochliomyia hominivorax (Diptera: Calliphoridae). Because other cases of
      coinfestation of flies and lice are on record, health workers are to be alerted
      about the possible pediculosis-myasis risk.

PMID- 19753835
TI  - [Persistent type 2 lepra reaction (erythema nodosum) and clofazimine-induced
      lethal enteropathy].
AB  - INTRODUCTION: Clofazimine enterophathy is a serious complication of clofazimine
      when used at high doses for treatment of type 2 lepra or or erythema nodosum
      leprosum. Objective. A woman is presented who had a delayed diagnosis of leprosy,
      persistent type 2 lepra reaction and lethal clofazimine enteropathy. MATERIALS
      AND METHODS: A 31-year-old woman presented leprosy symptoms over a 16-year period
      without medical diagnosis of her disease. During this period, type 2 lepra
      episodes occurred, but were not accurately diagnosed. These episodes became more
      severe during her second pregnancy. The patient and her family were interviewed,
      and her clinical history reviewed. RESULTS: After twelve years of medical
      consults, lepromatous leprosy was diagnosed, based on perforation of her nasal
      septum, with a bacterial index of 5. Her husband and a 12-year-old daughter have
      leprosy symptoms. During multidrug therapy, she presented with repeated type 2
      lepra reaction episodes for which she received daily clofazimine 400 mg doses.
      Two months after this treatment, severe and frequent episodes of intense
      abdominal pain began to occur. These persisted for more than a year and were
      managed with in-hospital administration of several classes of painkillers and
      antispasmodic medication, including morphine. She also presented with sporadic
      diarrhea, constipation, nausea, weight loss and mesenteric adenopathies. She died
      finally due to this intestinal condition. No autopsy was performed. CONCLUSIONS:
      The patient's clinical presentation suggested a clofazimine-induced lethal
      enteropathy, a complication not previously seen in Colombia. This connection was
      not recognized by the medical officers that treated the patient.

PMID- 19753836
TI  - [Four cases of Jarcho-Levin's syndrome in the province of Antioquia, Colombia].
AB  - Four cases of Jarcho-Levin's syndrome in the province of Antioquia, Colombia
      Jarcho-Levin's syndrome is a skeletal dysplasia with changes in the morphogenesis
      and costal vertebrae segmentation. It is manifested by hemivertebrae, fused
      vertebral bodies, absent vertebrae or fused ribs. This entity has also been
      called spondylo-costal or spondylo-thoracic dysplasia-dysostosis. This paper
      presents four cases evaluated at the Hospital University San Vicente de Paul,
      Medellin, Colombia. Three had family origins in southwestern Antioquia and one in
      Medellin, indicating the possibility of a predisposing genetic allele with
      elevated frequency in this population. The clinical and radiological
      manifestations were described, a well as the most notable complications, such as
      restrictive lung disease with permanent oxygen requirement (all 4 patients) and
      portal hypertension etiology (1 patient). The latter has not been reported
      previously as a manifestation of this syndrome.

PMID- 19753837
TI  - [Evidence-based medicine: an epistemological approach].
AB  - Evidence-based medicine gathers physician's experience and the best scientific
      evidence to make medical decisions. This proposal has been widely promulgated by
      medical opinion leaders. Despite a large literature supporting this practice, a
      formal discussion has not been established regarding its epistemological
      consequences in daily medical work. The main proposal of evidence-based medicine
      consists of choosing the best medical decision according to the best available
      results from scientific studies. Herein, the goal was to highlight inappropriate
      application of the scientific method used by physics to clinical science. The
      inaccuracy resides in describing health and disease in strictly numeric
      equivalents that can be homogenized on a continuous scale. Finally, the authors
      consider each diseased human being as a complex system, unique and particular,
      and that this being is defined by an historical background as well as current
      actual context. Therefore, evidence-based medicine possesses certain limitations
      that must be recognized in order to to provide better health care to patients.

PMID- 19753838
TI  - [Financial cost of early rheumatoid arthritis in the first year of medical
      attention: three clinical scenarios in a third-tier university hospital in
      Colombia].
AB  - INTRODUCTION: In Colombia, the cost burden of chronic diseases is not well known,
      either globally or in localized areas of the health system. Rheumatoid arthritis
      is one of most common chronic diseases, and represents a high cost for the health
      system. OBJECTIVE: The direct medical costs were estimated for rheumatoid
      arthritis patients in the in the first year of diagnosis at a level 3 university
      hospital in Colombia. MATERIALS AND METHODS: Three therapy settings for early
      rheumatoid arthritis patients were established in the first year of diagnosis
      according to national and international guidelines. Each setting included
      treatment with disease-modifying anti-rheumatic drugs or biologic therapy based
      on disease severity as measured by Disease Activity Score 28. All direct medical
      costs were included: specialized medical care, diagnostic tests and drugs. Cost
      information was obtained from the Central Military Hospital finance department in
      Bogota and the national manual of drug prices based on the "Farmaprecios" 2007
      guide, a reference in general use by health institutions. Results. The average of
      cost of medical care in patients with mild, moderate and severe disease was US
      $1689, $1805 and $23,441 respectively. The recommended retail prices of the
      medicines published in "Farmaprecios" was US $1418, $1821 and $31,931. When the
      charges levied by several major health institutions were compared, substantial
      increases were noted, US $4936, $7716 and $123,661, respectively. Drug costs
      represented 86% of total cost, laboratory costs were 10% and medical attention
      was only 4%. CONCLUSIONS: Drugs costs were the principal component of the total
      direct medical cost, and it increased 40 times when a biological therapy is used.
      Complete economic evaluation studies are necesary to estimate the viability and
      clinical relevance of biological therapy for early rheumatoid arthritis.

PMID- 19753839
TI  - Anti-tubercular activity of eleven aromatic and medicinal plants occurring in
      Colombia.
AB  - INTRODUCTION: Human tuberculosis is a contagious-infectious disease mainly caused
      by Mycobacterium tuberculosis. Although regimens exist for treating tuberculosis,
      they are far from ideal. Development of effective strategies for treatment of
      human tuberculosis has posed a challenge, considering the increase in infections
      associated with the human immunodeficiency virus and immunocompromised patients.
      Essential oils--volatile, aromatic oil extracts from plants--have been used in
      traditional treatment of many diseases; however careful investigation of these
      oils has not been undertaken with respect to treatments of tuberculosis.
      OBJECTIVE: The in vitro antitubercular activity of essential oils from 11
      medicinal plants grown in Colombia were assessed for efficacy as new medications
      (phytomedicines) for treatment of M. tuberculosis H37Rv. MATERIAL AND METHODS:
      Essential oil extraction and analysis were performed as described Stashenko et
      al. (2004). Minimal inhibitory concentrations were determined by a colorimetric
      macrodilution method, following the protocol described by Abate et al. (1998).
      Isoniazide and rifampin were used as control treatments. Bactericidal and
      bacteriostatic activity was measured using the method developed by the Clinical
      and Laboratory Standards Institute consigned in the M26-A protocol. RESULTS:
      Essential oils from Achyrocline alata and Swinglea glutinosa were the most active
      with minimal inhibitory concentrations of 62.5 +/- 0.1 and 100 +/- 36 microg ml(
      1), respectively. Carvacrol, thymol, p-cymene, 1,8-cineole, limonene, and beta
      pinene were the major components, most often identified in the 11 plant extracts
      of essential oils. Time-kill curve assays demonstrated the bacteriostatic
      activity of these essential oils. CONCLUSIONS: The essential oils from A. alata
      and S. glutinosa plants, and the components identified therein, are candidates as
      potential phytotherapeutic agents for human tuberculosis control.

PMID- 19753840
TI  - [Mutations in the BRCA1 gene (185delAG and 5382insC) are not present in any of
      the 30 breast cancer patients analyzed from eastern Colombia].
AB  - INTRODUCTION: Breast cancer is considered a worldwide public health problem, and,
      in Santander Province, Colombia, it is the first leading cause of morbidity and
      mortality by cancer in women. All cancers are considered genetic diseases, and
      mutations in BRCA (BReast CAncer) genes raises the risk for breast cancer by 60%
      80%. The current study searched for the two most frequent BRCA1 mutations
      reported in the Breast Cancer Core Information database. OBJECTIVE: The presence
      of specific mutations (185delAG, exon 2 and 5382insC, exon 20) was determined for
      the BRCA1 gene in women with familial/hereditary breast cancer. MATERIALS AND
      METHODS: The sample included 30 female patients using the oncology services in
      Bucaramanga, eastern Colombia; an informed consent, a questionnaire and a blood
      sample were obtained from each. The molecular analysis was done with PCR
      Mismatch, to detect the insertion or eliminatation of a restriction site, and
      enzymatic digestion methods (Hinfl or Ddel). RESULTS: Two of the most frequent
      BRCA1 mutations in the international database were not found in the 30 patients
      studied. CONCLUSION: Additional mutation screening techniques are necessary
      involving the entire BRCA1 gene, are necessary in order to better characterize
      the molecular epidemiology of breast cancer in Bucaramanga, Santander, Colombia.

PMID- 19753841
TI  - [Sand flies (Diptera: Psychodidae) of Guaviare Province, Colombia, with 4 new
      records for the country].
AB  - INTRODUCTION: Although cases of leishmaniasis have been reported in the province
      of Guaviare, Colombia, no entomological studies were included to identify the
      Lutzomyia sand fly vector species in that area. OBJECTIVE: Lutzomyia species were
      identified from four townships of Guaviare. Probable vectors were named based on
      those species involved in transmission in other areas. MATERIALS AND METHODS:
      Sampling was undertaken with CDC light traps suspended at heights between 1.5 m
      and 9 m. Additional sand flies were collected with Shannon traps and by
      aspiration of adult flies from daytime resting sites. RESULTS: Sand flies
      belonging to 37 different species were collected. 35 of them were recorded for
      the first time in Guaviare Province. Four species were new records for Colombia:
      Lutzomyia begonae, L. campbelli, L. sericea and L. nematoducta. The most abundant
      species were L. hirsuta 24.3% (148/610), L. yuilli 15.2% (93/610), L. davisi
      10.3% (63/610), followed by L. fartigi, L. carrerai, L. antunesi, L.
      flaviscutellata and L. olmeca bicolor. CONCLUSION: Seven of these species of have
      been associated previously with endemic or epidemic transmission of
      leishmaniasis.

PMID- 19753842
TI  - [Flu vaccine effectiveness: a metaanalysis].
AB  - INTRODUCTION: Seasonal influenza is a disease of great interest in public health
      due to its high rates of infection and big costs, especially in high-risk
      population. This situation has motivated studies related to development of
      control measures necessary to mitigate its impact. Immunization constitutes a key
      role in providing the necessary interventions; however, little information is
      available about its effectiveness as public health measure in tropical countries.
      OBJECTIVE: The vaccine effectiveness was evaluated by means of published results
      in the scientific literature. MATERIALS AND METHODS: Meta-analysis techniques
      were used to summarize the results of epidemiological analytical studies. A
      critical evaluation was undertaken for each study to identify the potential
      biases and methodological limitations. RESULTS: Two hundred and fifty-seven
      relevant studies were located, of which 28 were included in the analysis. The
      pooled estimator of the vaccine effectiveness for hospitalization was 0.74 [95%
      CI 0.68-0.81] in older adults (65 years and older) in cases-control studies. For
      cohort studies, the obtained estimator was 0.80 [95% CI 0.68-0.91]. CONCLUSION:
      Other conclusions were analyzed, and in general, a protective effect was
      demonstrated in the vaccine. About 1,200,000 were involved, 530,000 of them were
      vaccinated. Geographically, the analyzed studies came from developed countries in
      Europe, America and Asia.

PMID- 19753843
TI  - [Mortality by avoidable causes in preschool children].
AB  - INTRODUCTION: The infant-mortality rate in children aged less than five is an
      indicator of the general state of health of a population and directly reflects
      the quality of life and the level of socio-economic development of a country.
      OBJECTIVE: Avoidable mortality was assessed in preschool children as a reflection
      of Colombia quality of life and socio-economic development. MATERIALS AND
      METHODS: Mortality trends were analyzed in preschool children aged less than five
      throughout Colombia during a 20-year period from 1985-2004, and focused on
      mortality causes that were considered avoidable. This was a descriptive,
      retrospective study; the sources of information were Departamento Administrativo
      Nacional de Estadistica records of deaths and population projections 1985-2004.
      Mortality rate due to avoidable causes was the statistical indicator. RESULTS: In
      children aged less than one, the reducible mortality due to "early diagnosis and
      medical treatment" occupied the first place amongst causes for every year of the
      study period and accounted for more than 50% of recorded deaths. In children aged
      1 to 4, the category "other important reducible causes" was associated with 40%
      of recorded deaths-deaths due mainly to respiratory diseases. Over the 20-year
      period, the avoidable mortality rate decreased by 34% in children aged less than
      one, in children 1-4, it decreased by 23%. CONCLUSIONS: Although the infant
      mortality rate in preschool children was reduced, the decrease was small, from
      80% to 77%. The situation requires more analysis with respect to strategies in
      public health, particularly concerning preventable diseases of the infancy.

PMID- 19753844
TI  - [Association between polymorphism in uncoupling proteins and type 2 diabetes in a
      northwestern Colombian population].
AB  - INTRODUCTION: The uncoupling proteins belong to the family of anion transporting
      proteins which uncouple the ATP production from the mitochondrial respiration,
      cause proton leakage through the inner mitochondrial membrane, and release energy
      as heat. Although uncoupling protein function has not been well established,
      specific polymorphisms in these proteins have been associated with type 2
      diabetes mellitus, obesity and insulin resistance. OBJECTIVE: The association was
      assessed between the polymorphisms in uncoupling protein genes 1, 2 and 3 genes
      and type 2 diabetes mellitus. MATERIALS AND METHODS: In a northwestern Colombian
      population, 545 diabetes cases and 449 controls were investigated for presence of
      14 polymorphisms in uncoupling protein genes (3826A/G, ID 45, 2723T/A, 1957G/A,
      866G/A, and 55C/T) by PCR and PCR-RFLP. Single associations were evaluated by chi
      square test, and bayesian logistic regression analysis was done including as
      covariates the individual admixture estimates obtained by 54 informative markers
      for European, African and Amerind ancestry. RESULTS: Association between type 2
      diabetes mellitus and the polymorphisms 3826A (OR=0.78; 95% CI = 0.63-0.97; p =
      0.02) and 55 C (OR = 1.41; 95% CI = 1.04-1.92; p = 0.03) and the haplotype D45,
      866G, 1957G, 2723T, and 55C (OR = 1.26; 95% CI = 1.02-1.56; p = 0.03) were found.
      These associations remained after adjustment using individual genetic admixture
      estimates. CONCLUSION: Some alleles of uncoupling protein genes 1, 2 and 3, and
      their haplotypes confer risk to type 2 diabetes in a northwestern Colombian
      population.

PMID- 19753845
TI  - [Life cycle of Triatoma dimidiata latreille, 1811 (Hemiptera, Reduviidae) under
      laboratory conditions: production of nymphs for biological tests].
AB  - INTRODUCTION: Despite the importance of Triatoma dimidiata as a vector of Chagas
      disease, little is known of its life cycle and the efficient production of these
      insects for biological tests. OBJECTIVE: Life cycle characteristics in the
      laboratory were described and optimum nutritional conditions were established for
      the efficient production of nymphs V stage for biological tests. MATERIALS AND
      METHODS: We determined the time of development of the nymphal stage under
      controlled laboratory conditions until reaching the adult stage. In a massive
      rearing of stage V nymphs, fed and weighted after varying periods of fasting,
      distributed in weight ranges to obtain the largest proportion of individuals.
      RESULTS: The time mean from egg to adult was 269 days, with a wide range of
      duration (174 to 598 days) and the times required for 1st, 2nd, 3rd, 4th and 5th
      stage development was 33, 37, 41, 61 and 69 days, respectively, with a mortality
      of 22%. The optimum treatment was 22 days of fasting, in which 76% of the nymphs
      reached stage V with a weight range from 201 to 300 mg. CONCLUSION: Triatoma
      dimidiata presented development time with broad range for some individuals,
      possibly due to the irregularity in the food availability. A homogenous weight
      range was attained with a regime of 22 days of fasting with an optimum production
      of stage V nymphs.

PMID- 19753846
TI  - [Epidemiological analysis of patients coinfected with Chagas disease and
      cysticercosis].
AB  - INTRODUCTION: Among inhabitants of endemic areas in the developing world,
      infection with the larva of Taenia solium (cysticercosis) may possibly induce a
      state of immunosuppression in the host, thereby increasing the risk of multiple
      infections after exposure to other parasites, such as Trypanosoma cruzi.
      OBJECTIVE: Increase in the epidemiological occurrence of infection was assessed
      for Trypanosoma cruzi (Chagas disease) in patients with cysticercosis. MATERIALS
      AND METHODS: At the University Hospital in Uberaba, Minas Gerais, Brazil, data
      were obtained from autopsies performed between 1970-2004 on 1,501 subjects older
      than 15 years of age. Cases were divided into four groups: (1) no infection, (2)
      cysticercosis only, (3) Chagas disease only, and (4) cysticercosis coinfected
      with Chagas disease. Race, gender and age data were analyzed. RESULTS: More than
      half of the cases showed no infection (848 cases or 56.5%); Chagas disease was
      found in 611 patients (40.7%); 72 cases (4.8% of the autopsies) had cysticercosis
      and 30 of them (41.7%) were co-infected with Chagas disease. White race and male
      gender were predominant in all groups. The youngest median age was found in the
      non-infected group (46 years), followed by those with Chagas disease without
      cysticercosis (49 years) and those coinfected with cysticercosis and Chagas
      disease (57.5 years). CONCLUSION: Presumably, all patients had a similar exposure
      to both parasites. However, in this study population, Chagas disease was
      approximately 10 times more frequent in patients coinfected with cysticercosis.

PMID- 19753847
TI  - [Prevalence of autoantibodies against autonomic receptors in patients with
      chronic cardiopathies].
AB  - INTRODUCTION: Chagas disease is the main cause of chronic myocardiopathy in
      Central America. The mechanisms proposed for this cardiac pathology during the
      chronic phase remain controversial. Several studies have detected the presence of
      circulating autoantibodies against beta-adrenergic and cholinergic muscarinic
      receptors of the myocardium in patients with Chagas disease. These autoantibodies
      can trigger intracellular signals and modify the cardiac function during the
      progression of the disease. OBJECTIVES: The serological frequency of these
      autoantibodies was compared among patients with chronic Chagas disease, patients
      with other cardiopathies and healthy controls. MATERIALS AND METHODS: The
      prevalence of autoantibodies against beta-adrenergic and cholinergic muscarinic
      receptors was determined in four groups of Panamenian patients: 53 chagasic
      patients, 25 serologically negative patients with cardiac insufficiency, 25
      patients with cardiac arrhythmia and 25 healthy individuals. RESULTS: The
      antibodies against autonomic receptors were more frequently observed in patients
      with chronic chagasic cardiomyopathy (24.5%) compared to the cardiac
      insufficiency group (20.0%) and the cardiac arrhythmia group (16.0%). The
      proportion of autoantibodies was significantly different between the groups with
      chronic chagasic cardiomyopathy and healthy controls (24.5% versus 0%; p =
      0.015). Of the 53 chronically infected chagasic patients, 48 (90%) showed some
      degree of cardiac dysfunction. CONCLUSIONS: The frequency of autoantibodies
      against autonomic receptors is significantly increased in patients with chronic
      Chagas disease and in patients with other cardiopathies.

PMID- 19753848
TI  - [Excitation-contraction coupling in skeletal muscle: questions remaining after 50
      years of research].
AB  - The excitation-contraction coupling mechanism was defined as the entire sequence
      of reactions linking excitation of plasma membrane to activation of contraction
      in skeletal muscle. By using different techniques, their regulation and
      interactions have been studied during the last 50 years, defining until now the
      importance and origin of the calcium ion as a contractile activator and the main
      proteins involved in the whole mechanism. Furthermore, the study of the
      ultrastructural basis and pharmacological regulation of the excitation
      contraction coupling phenomenon has begun. The excitation-contraction coupling is
      thought to be altered in situations as ageing, muscle fatigue and some muscle
      diseases. However, many questions remain to be answered. For example, (1) How
      excitation-contraction coupling develops and ages? (2) What role does it play in
      muscle fatigue and other diseases? (3) What is the nature of the interaction
      between the proteins believed to be involved? The present review describes
      excitation-contraction coupling in skeletal muscle and techniques used to better
      understand it as an introduction for discussing unanswered questions regarding
      excitation-contraction coupling.

PMID- 19753849
TI  - [Re: the editorial in number 4, volume 28, 2008. "Cervical cancer control in
      Colombia: achievements and challenges of cytology based programs"].

PMID- 19753850
TI  - Our journey to Africa and the stirrings of good hope.

PMID- 19753851
TI  - Weigh in on the future of nursing.

PMID- 19753852
TI  - Trinitas School of Nursing, Elizabeth, New Jersey, became certified nurse
      educators.

PMID- 19753853
TI  - Evaluating first-year nursing students' ability to self-assess psychomotor skills
      using videotape.
AB  - Developing confidence in self-assessment is an important skill in becoming a self
      regulated learner. This article describes the process undertaken by a group of
      educators of incorporating self-assessment in combination with psychomotor skill
      development with freshman students. Students were videotaped performing a wound
      dressing change; the videotaping was immediately followed by a self-assessment of
      their performance using a faculty-generated checklist. Comparison of faculty and
      student ratings revealed the tendency for students to overrate their performance
      and identified discordance between students and faculty on several steps of the
      procedure. These evaluation findings are discussed and future directions
      explored.

PMID- 19753854
TI  - Textbooks on tap: using electronic books housed in handheld devices in nursing
      clinical courses.
AB  - Changing technology is creating new ways to approach nursing education and
      practice. Beginning in 2003, using a quasi-experimental design, this project
      introduced personal digital assistants (PDAs) as a clinical tool to five
      experimental and control groups of students and faculty. The handheld device, or
      PDA, was loaded with e-books for clinical practice. Differences in learning
      styles and preferences emerged during the different phases of the study. Students
      were quickly able to master the technology and use the device effectively,
      reporting that they liked the concise nature of the information obtained. No
      students expressed dissatisfaction or regret at being in the experimental group.
      Results and implications for clinical practice, education, and library resources
      are discussed.

PMID- 19753855
TI  - A pilot project to evaluate the academic performance, abilities, and satisfaction
      of second-degree students.
AB  - The literature on students matriculated in the growing number of second-degree
      nursing programs in the United States typically describes them as exceptional on
      many parameters of interest. The experience at the authors' university in an
      integrated second-degree baccalaureate nursing program did not support prevailing
      notions regarding these students. The purpose of this pilot project was to
      evaluate the performance and satisfaction of second-degree students in comparison
      to traditional students. The Learning and Study Strategies Inventory, a
      standardized exit examination, the nursing grade point average (GPA), and focus
      groups were used in the evaluation. Findings showed little difference between
      second-degree students and traditional students on the Learning and Study
      Strategies Inventory and no difference in exit examination scores and nursing
      GPA. Social and learning differences were apparent as a result of the focus group
      experience.

PMID- 19753856
TI  - Faculty perceptions of academic advising: "I don't get no respect".
AB  - Best practices in teaching and learning may begin with effective academic
      advising. Nursing research and scholarship in the area of advising, however, is
      virtually nonexistent. The purpose of this exploratory study was to determine
      nurse faculty perceptions of the characteristics and functions of an effective
      academic adviser. The study was conducted at a comprehensive state university in
      southeastern Minnesota. Content analysis of 17 completed questionnaires was
      consistent with extant education and pedagogical research. Authenticity and
      accountability were unique characteristics of an effective adviser identified by
      participants in this study. The findings will facilitate faculty development in
      the area of academic advising and help improve services to students. Further, the
      results have helped identify areas for continuing scholarship in nursing.

PMID- 19753857
TI  - Illness perception of nursing students regarding myocardial infarction.
AB  - Health interventions aimed at secondary prevention of myocardial infarction (MI)
      are important. Patients' illness perceptions influence adherence behaviors and
      actions. Providing adequate infomation about the disease and lifestyle
      interventions is an important task for health care professionals. Therefore, a
      question of interest is how health care professionals perceive myocardial
      infarction themselves. The aim with the present study was to investigate how
      nursing students at a Swedish university perceived MI and to determine whether
      their illness perceptions changed during their six-term program of education.
      Illness perception was measured using the Revised Illness Perception
      Questionnaire (IPQ-R) in a sample of 196 students enrolled in terms 2, 4, and 6
      of the nursing program. A quasi-experimental design was used. Illness perceptions
      among nursing students were also compared to illness perceptions in a group of
      patients with coronary heart disease. The belief that it is possible to control
      MI through medical treatment became stronger during the course of nursing
      education. Nursing students were found to view the consequences of MI as serious,
      but also as medically treatable and responsive to lifestyle changes.

PMID- 19753858
TI  - Creating environments that foster academic integrity.
AB  - A number of studies related to academic dishonesty within the nursing student
      population have been published; however, little has been written in the nursing
      literature regarding academic integrity and means of promoting this value. In
      addition to the many short-term solutions to prevent cheating and dissuade
      academic misconduct that are offered, solutions that promote long-term affective
      changes underlying the acquisition of academic integrity are needed. This article
      provides a context for discussions related to academic integrity, explores issues
      facing faculty when dealing with this challenge, and offers short-term and long
      term strategies for creating environments that foster academic integrity.

PMID- 19753859
TI  - Enhancing geriatric content in a baccalaureate nursing program.
AB  - As the United States population ages, it is important that nursing faculty
      adequately prepare undergraduate students to provide optimal nursing care for
      older adults. By 2030, estimates are that one in five Americans will be over the
      age of 65. Older adults often have complex health issues and use more health care
      resources than other age groups. Over the last 10 years, schools of nursing have
      been increasingly enhancing the gerontological content in their curricula.
      However, to ensure that nurses will have the specialized geriatric knowledge and
      skills to improve health outcomes, expansion and enhancement of geriatric
      curricula must be an ongoing process. This article presents information regarding
      the process that one university used to evaluate and revise its curriculum using
      geriatric competences and recommendations set forth by the Hartford Foundation
      and AACN.

PMID- 19753860
TI  - The application of problem-based learning in Chinese baccalaureate nursing
      education.

PMID- 19753861
TI  - Essential textbooks and journals for the master of science in nursing: educator
      tracks.

PMID- 19753862
TI  - Teaching with and about technology: providing resources for nurse educators
      worldwide.

PMID- 19753863
TI  - Update on the NLN/Johnson & Johnson Faculty Leadership and Mentoring Program.

PMID- 19753864
TI  - Hearing the stories behind our patients' words: an excerpt.

PMID- 19753865
TI  - The saddest debate of all.

PMID- 19753866
TI  - The RCn's neutral stance 'hugely significant' in assisted suicide debate.

PMID- 19753868
TI  - From nursing leader to patients' champion.
AB  - Roswyn Hakesley-Brown is using her considerable nursing experience to champion
      the cause of patients through the Patients Association.

PMID- 19753867
TI  - Compassion through human connection.
AB  - NHS Lothian and Napier University in Edinburgh are collaborating on a programme
      to ensure compassion becomes an integral characteristic of nursing education,
      practice and leadership.

PMID- 19753869
TI  - A tool for diabetes.
AB  - Improving the care of inpatients who have diabetes but are admitted for other
      reasons is the aim of ThinkGlucose.

PMID- 19753870
TI  - Celebration culture.

PMID- 19753871
TI  - Withholding truth from patients.
AB  - The issue of whether patients should always be told the truth regarding their
      diagnosis and prognosis has afforded much debate in healthcare literature. This
      article examines telling the truth from an ethical perspective. It puts forward
      arguments for and against being honest with patients, using a clinical example to
      illustrate each point.

PMID- 19753872
TI  - Effective strategies for prevention and control of Gram-negative infections.
AB  - Infections caused by Gram-negative bacteria such as Pseudomonas, Klebsiella,
      Proteus and Acinetobacter have been a major problem in healthcare settings for
      many years. Overlooked in government targets and unknown to patients, these
      infections present considerable challenges for effective infection prevention and
      control. Key strategies for prevention and control focus on contact precautions,
      the management of invasive devices and maintaining a clean, dry environment to
      prevent the build-up of environmental reservoirs and cross-infection.

PMID- 19753873
TI  - Developments in the management of patients with sepsis.
AB  - Sepsis is associated with a high incidence of mortality and morbidity, however
      with appropriate strategies for monitoring and early targeted intervention
      mortality rates decline. This article examines the basic pathophysiology of the
      inflammatory response to tissue injury and the effects this has on circulation. A
      partnership of the Society of Critical Care Medicine, the European Society of
      Intensive Care Medicine and the International Sepsis Forum has developed the
      surviving sepsis strategy, which includes the sepsis six treatment pathway and
      early goal-directed therapy incorporating the six-hour care bundle.

PMID- 19753874
TI  - Isolation precautions.

PMID- 19753875
TI  - Man about the house.

PMID- 19753876
TI  - Bearing witness.

PMID- 19753878
TI  - Coming to California?

PMID- 19753877
TI  - Century of support.

PMID- 19753879
TI  - Oral health and the demand for dental care.

PMID- 19753880
TI  - The demand for dental care and financial barriers in accessing care among adults
      in California.
AB  - Receiving dental care is positively related to having dental insurance; being
      female; increasing age; being white, Hispanic or Asian; higher levels of
      education; higher levels of family income; better health status; and being
      unmarried. In contrast, being more likely to perceive financial barriers to
      receiving needed dental care is positively related to lacking dental insurance,
      being female, being younger, being black or other race, having less education,
      lower family income, and having worse health status.

PMID- 19753881
TI  - The effect of functional limitations on the demand for dental care among adults
      65 and older.
AB  - In California, adults living in the community who have two or more of six
      functional limitations in activities of daily living outnumber adults who live in
      skilled nursing, intermediate care, and congregate living facilities by almost
      2:1. In 2003, approximately 106,000 elderly women living in the community
      experienced two or more limitations in activities of daily living and were thus
      40 percent less likely to access dental care relative to elderly women with fewer
      limitations.

PMID- 19753882
TI  - Adult oral health status in California, 1995-2006: demographic factors associated
      with tooth loss due to disease.
AB  - The most recent 2006 estimates indicate that 60 percent of California adults did
      not experience tooth loss due to disease. However, about 39 percent were missing
      one or more teeth due to disease, and another 1 percent were edentulous. In an 11
      year (1995-2006) pooled multivariate analysis, California adults who were older,
      less educated, racial/ethnic minorities, current or former smokers, or had lower
      annual incomes were more likely to be missing teeth.

PMID- 19753884
TI  - Economizing.

PMID- 19753883
TI  - The oral health status of adults 65 and older in California:1995-2006.
AB  - There has been no overall change in the oral health of adults aged 65 years and
      older from 1995 to 2006. However, approximately 75 percent of the elderly in
      California were missing one or more teeth due to disease in 2006. Californians
      who are older, black, less educated, have low family income, and are current or
      former smokers are more likely to be missing teeth.

PMID- 19753885
TI  - Elementary my dear Watson.

PMID- 19753886
TI  - Measuring agenda for change?

PMID- 19753887
TI  - Agency nursing in Australia.

PMID- 19753888
TI  - Pleural effusion: diagnosis and management.
AB  - Pleural effusion is defined as an accumulation of fluid in the pleural space in
      excess of 15 to 20 mls. The aetiology for the development of a pleural effusion
      includes changes in hydrostatic or colloid-osmotic pressure of pleural and
      pulmonary capillaries, changes in pleural vascular permeability and impaired
      lymphatic drainage. About 5% to 12% of patients referred for emergency medical
      treatment are diagnosed with a pleural effusion, making it a common finding on
      hospital admission. The excess of pleural fluid may be triggered by pleuro
      pulmonary infection, malignancy, or conditions of cardiac, renal or hepatic
      origin. Subsequent management is guided mainly by aetiology and to a lesser
      degree by symptoms. This paper provides a review of pathophysiology, diagnosis
      and management of the condition and addresses specific issues regarding the
      perioperative care of these patients.

PMID- 19753889
TI  - Perioperative communication.
AB  - This article has raised the issue of effective communication within the
      perioperative setting. There are many methods for sending information from one
      person to another. Most important in effective communication is the clarity of
      the message and how practitioners check that the recipient understands the
      intended point. If key aspects in the communication process are not fully
      understood or utilised, then we subject our patient and our colleagues to
      potential risk. If poor communication causes untoward and unacceptable
      consequences then the perioperative practitioner will be accountable for their
      actions in law and to their regulatory body. The responsibility of effective
      communication lies with the individual practitioner first and foremost. To
      prevent poor communication taking place, they should ensure that they have the
      correct skills to communicate effectively, be that by listening, reflecting on
      experiences or writing.

PMID- 19753890
TI  - Morphine delays discharge following ambulatory surgery: a prospective
      institutional study.
AB  - INTRODUCTION: Morphine is used regularly in day surgery despite its known side
      effects. We assessed whether this delayed discharge. PATIENTS AND METHODS: 100
      patients were divided into 2 groups: 50 patients received morphine and 50
      patients received non-morphine analgesia. Demographic data and reasons for
      delayed discharge were recorded. RESULTS: 73% of all major cases received
      morphine compared to only 19% of minor cases. Operative and recovery times were
      significantly greater in the morphine group. 58% of patients given morphine had a
      delayed discharge compared to 14% of patients not given morphine. CONCLUSIONS:
      Morphine use in day surgery is associated with increased operating and recovery
      times and higher rates of delayed discharge.

PMID- 19753891
TI  - Perioperative nurses' perceptions and experiences of continuing professional
      education.
AB  - This article presents an overview of perioperative nurses' perceptions and
      experiences of continuing professional education (CPE). Four themes emerged from
      23 interviews: attitudes and culture (background); deciding to study (going in);
      student experience (process); and outcomes (going out). My findings indicate
      transferability of other studies to perioperative nursing, and suggest that CPE
      is associated with increased social status and doctor-nurse collaboration. My
      work also illuminates the concept of 'secret study'.

PMID- 19753892
TI  - Elizabeth Kenny: an early and controversial physiotherapist.

PMID- 19753893
TI  - The message is clear: hope and pressure to eradicate extreme global poverty
      prevail.

PMID- 19753894
TI  - CPT coding patterns at nurse-managed health centers: data from a national survey.
AB  - Nurse-managed health centers (NMHCs) play an important role in delivering health
      care services to a wide range of communities and often serve as our nation's
      safety net providers. Unfortunately, NMHCs struggle to remain in business for a
      variety of reasons, including underdeveloped business practices. Until now, NMHCs
      had only data from the Centers for Medicare and Medicaid Services and the Medical
      Group Management Assocation for comparison with coding patterns in individual
      centers. This article is the first published report of national data for NMHCs
      that is available for comparison. Providers need to possess financial acumen to
      remain open for business. Assessment of CPT coding patterns is a key strategy to
      support long-term sustainability.

PMID- 19753895
TI  - Retaining an aging nurse workforce: perceptions of human resource practices.
AB  - The expected retirement of the largest cohort of nurses will push the RN
      workforce below projected need by 2020. The challenges of managing a nursing
      workforce with the majority of nurses over 45 years of age are now necessitating
      attention to polices for recruitment and retention of older nurses, particularly
      in rural areas. This convenience sample study employed a mailed survey to
      investigate perceptions of nurses in 12 institutions (four hospitals, seven home
      health agencies, and one nursing home serving a small rural state). The goal was
      to explore rural RNs' perceptions of intent to stay in their current position,
      with their organization, and employment as a nurse; organizational and unit-level
      culture regarding older nurses in the workplace; importance of specific human
      resource practices/policies to their own intention to stay; and extent to which
      these human resource practices/policies are currently done. The results indicate
      that although there are similarities across age cohorts, important differences
      exist that can be addressed to create career-span sensitive policies and
      practices. This study provides an indicator of progress or lack of progress in
      addressing older nurse recruitment and retention, and also offers guidance for
      differentiating policies and practices for younger and older nurses.

PMID- 19753896
TI  - An interview with Thomas W. Chapman, EdD, MPH president and chief executive for
      the HSC Foundation. Interview by Veronica D. Feeg.

PMID- 19753897
TI  - Using innovation to assess nursing workforce in Arizona: a collaborative
      approach.
AB  - The process of using nurse license renewal data to generate the information
      needed to measure and project the supply of RNs, LPNs, and APNs in a state is
      described. The use of licensing applications as the foundation to which time
      varying survey questions can be added offers a continuing record of the behavior
      of the nursing workforce for all nurses in a state workforce. A significant added
      benefit is this can occur at a fraction of the cost of a one-point-in-time survey
      of even a small sample of nurses. Other states could benefit from adopting a
      similar approach of collaboration between health care systems (e.g., hospital
      associations), boards of nursing, and academia. Such collaboration would allow
      nursing administrators and academia alike the ability to accurately predict
      nursing workforce needs, thus facilitating operational decision making and
      strategic planning.

PMID- 19753898
TI  - Estimating the cost of professional developmental activities in health
      organizations.
AB  - Continuing professional development and a lifelong learning perspective are
      necessary as a consequence of ever-faster processes of development in nursing and
      medical knowledge, and changes in health care systems and strategies. The
      necessity to use time for professional development to secure and develop quality
      in care must be defended. As a consequence, there is a need for knowledge about
      the cost of professional development activities. The model presented in this
      study presents an overview of all costs involved in an activity. Being aware of
      these costs and pinpointing where they belong in the organization can help
      nursing leaders present accurate arguments when defending and promoting
      professional developmental activities.

PMID- 19753899
TI  - What you permit, you promote.
AB  - The leader establishes the expectations and the organization follows. These
      expectations can be very permissive with no recognizable structure, or the
      expectations can be clear and reasonable. What the leader permits becomes the
      cultural norms of the organization. The leader must take a "no-compromise"
      position when actions violate values and standards. Passive leaders and leaders
      who are held hostage by the excuse of personal issues generate a rationale for
      challenging the no-compromise stance and create mediocrity. When staff own the
      organization's values and standards, they become the standard bearers, coaches,
      and enforcers of the drive to excellence.

PMID- 19753900
TI  - Can the nursing profession win the game?
AB  - The ebb and flow of a basketball game is analogous to the nursing profession's
      recent past, its current state, and where the profession is heading. The metaphor
      of a basketball game provides a way of describing the timing of events that have
      shaped nursing over the past 20 years, and whether and how the next 15 years will
      be looked upon by historians as the greatest period in the history of the nursing
      profession. For this outcome to occur, nurses and the profession's leaders must
      see that the set of third quarter challenges are opportunities to deepen
      nursing's social relevance and its commitment to increase the health of people.

PMID- 19753901
TI  - Growing ambulatory care nurse leaders: building talent from the primed pipeline.
AB  - Leadership succession planning is an extremely important exercise for individuals
      and organizations to prepare for ambulatory health care in the future. There are
      several opportunity points and approaches to consider for identifying emerging
      leaders and developing leaders. Ambulatory care nurses should consider their own
      potential for leadership and take steps to develop their leadership competencies.

PMID- 19753902
TI  - The evolving voice of nursing in health care reform.

PMID- 19753903
TI  - Oral health at risk from cutbacks.

PMID- 19753904
TI  - Snapshot of dentists' attitudes.

PMID- 19753905
TI  - A changing profession.

PMID- 19753906
TI  - Dental nursing across Ireland.

PMID- 19753907
TI  - An effective bleaching technique for non-vital, discoloured teeth in children and
      adolescents.
AB  - Discolouration of a permanent incisor may have a significant social impact on
      children and adolescents. Intervention should be minimally destructive of tooth
      tissue and should not compromise future restorative options. This paper reviews
      the technique of inside/outside bleaching, and proposes it as an efficient,
      effective and acceptable method for use in the compliant younger patient with an
      unaesthetic non-vital tooth.

PMID- 19753908
TI  - Pericoronitis: treatment and a clinical dilemma.
AB  - Pericoronitis is an infection associated with impacted lower third molars that
      can necessitate the removal of these teeth. The clinical features of this
      condition are described and its treatment outlined, emphasising local measures. A
      case of pericoronitis in a 52-year-old patient is discussed, which illustrates
      the risks and benefits of removal of wisdom teeth; removal can lead to nerve
      damage, retention can precipitate serious, even life-threatening infection.

PMID- 19753909
TI  - Identifying orthodontic problems.

PMID- 19753910
TI  - Universal health insurance.

PMID- 19753911
TI  - Halt the impending federal takeover of health care.

PMID- 19753912
TI  - Early treatment of tick borne illnesses.

PMID- 19753913
TI  - What's bugging you now?

PMID- 19753914
TI  - Deja vu--maybe?

PMID- 19753915
TI  - Ellis Fischel Cancer Center needs Missouri's support.

PMID- 19753916
TI  - President Obama's health problems.

PMID- 19753917
TI  - Infectious risks for travelers to the tropics.
AB  - This paper is a brief overview of travel medicine with an emphasis on infectious
      disease risks for travelers to the tropics such as traveler's diarrhea, malaria,
      and vaccine preventable illnesses.

PMID- 19753918
TI  - HIV and aging: two converging epidemics.
AB  - With the aging of the Human immunodeficiency virus (HIV) epidemic, we are now
      faced with unprecedented and complex challenges, which need to be addressed in
      order to maximize care of the older HIV-infected population. Older persons have
      greater comorbidity than their younger counterparts. The compound effects of HIV
      infection, its treatment and increasing age on the incidence and prevalence of
      cardiovascular disease, malignancies, cognitive impairment, depression and
      frailty are of increasing concern.

PMID- 19753919
TI  - Skin and soft tissue infections due to CA-MRSA.
AB  - Infections caused by community-acquired methicillin-resistant Staphylococcus
      aureus (CA-MRSA) have become epidemic over the last decade. It causes a spectrum
      of diseases in humans but skin and soft tissue infections predominate. Molecular
      virulence factors in CA-MRSA are incompletely understood. In this article, the
      epidemiology, presentation, treatment, and surveillance of skin and soft tissue
      infections due to CA-MRSA are reviewed.

PMID- 19753920
TI  - Hematogenous vertebral osteomyelitis.
AB  - Hematogenous vertebral osteomyelitis is an increasingly important consideration
      in the differential diagnosis of patients presenting with back pain even in the
      absence of fever. The incidence of this disease is increasing and physicians must
      maintain a high index of suspicion to make a prompt diagnosis. In patients with
      progressive neurologic deficits, urgent diagnosis is imperative, as the window
      for necessary surgical intervention is narrow. Magnetic resonance imaging is the
      preferred radiologic modality because of its sensitivity. Bone biopsy is the gold
      standard for diagnosis and is usually performed percutaneously using CT-guidance.
      Antimicrobial therapy of at least six weeks in duration is recommended and should
      be tailored to pathogens recovered from bone biopsy culture. With improved
      diagnostic techniques and prompt management, adverse outcomes associated with a
      delay in diagnosis can be avoided.

PMID- 19753921
TI  - The current state of viral diagnostics for respiratory infections.
AB  - Rapidly determining the viral etiology of respiratory infections leads to more
      effective treatment and prevention. Traditional tests to diagnose respiratory
      viruses include cell culture, serology, and antigen detection assays. These
      methods differ in cost, time to results, and technical difficulty. Nucleic acid
      amplification tests such as PCR are more sensitive than the traditional assays
      and provide results quickly, while DNA microarrays offer a powerful method for
      the discovery of novel respiratory viruses.

PMID- 19753923
TI  - Emerging concepts of biofilms in infectious diseases.
AB  - Bacteria are known to coalesce into microbial communities, termed biofilms.
      Although traditionally regarded as environmental phenomena, bacterial biofilms
      are increasingly considered to play a role in many human infections. Biofilms are
      most often evoked in the context of chronic infections that are refractory to
      current antibiotic regimens or infections that recur despite an acute response to
      therapy. Here we consider the available evidence for the involvement of biofilms
      in infectious diseases and their potential significance.

PMID- 19753922
TI  - Clostridium difficile infection: a re-emerging threat.
AB  - Clostridium difficile infection is an important health care-associated infection.
      The incidence and severity of C. difficile infection are increasing. Recent C.
      difficile infection outbreaks with high proportions of severe outcomes have been
      linked to an emerging, hypervirulent strain of C. difficile. Recently recognized
      risk factors of C. difficile infection include fluoroquinolone exposure and
      gastric acid suppression. Effective prevention measures for C. difficile
      infection include contact precautions and antimicrobial stewardship. Awareness of
      C. difficile infection is critical to provide appropriate clinical care.

PMID- 19753924
TI  - Spinal surgery: an unusual case of spinal epidural abscess.
AB  - Southeast Missouri Hospital in Cape Girardeau, Missouri, admitted a patient from
      an outside hospital with back pain and progressive quadriparesis. Imaging
      revealed an extensive spinal epidural abscess that extended from the
      craniocervical junction to the sacral spine. Because of the patient's critical
      condition and the need to minimize the duration of surgery and anesthesia, two
      surgical teams simultaneously operated on the patient on the day of admission.
      One team performed a decompressive laminectomy of C1 through C7 and T1 through
      T6, while the other team performed, through a separate skin incision, a
      decompressive laminectomy on T11, L2, L3, and L4 as well as partial evacuation of
      a psoas abscess. The extensive laminectomies were required due to the adherent
      granulomatous nature of the abscess. Simple irrigation and intraoperative
      aspiration with suction was ineffective. The patient remained in the hospital for
      approximately three weeks and was discharged to a long-term acute care facility.
      Over the next five months her motor function gradually improved and she was
      discharged to home. Currently, she remains at home, free of significant pain and
      able to ambulate independently.

PMID- 19753925
TI  - Ehrlichia ewingii in an immunocompetent adult.
AB  - The third Ehrlichia infection described in humans in the United States is
      reviewed. This rare zoonosis was first published in 1999. This case report that
      expands the clinical paradigm is described. A 57-year-old immunocompetent adult,
      unlike previously published reports, did not cross react with Ehrlichia
      chaffeensis.

PMID- 19753926
TI  - Tick-borne febrile illnesses lacking specific symptoms.
AB  - We report here one case of tularemia, one case of human monocytic ehrlichiosis,
      and one case of febrile illness most consistent with tularemia with titers
      suggestive of Rocky Mountain spotted fever in residents of three south-central
      Missouri counties. All three cases had with nonspecific symptoms of a febrile
      illness. All three patients had a history of a tick bite, common in south-central
      Missouri, but only two patients reported the tick bite when first seen. In these
      three cases, the severity of the illness provided a clue that led to a diagnosis
      of tick-borne febrile illnesses by confirmatory serology in two cases. It is very
      important that physicians be aware of these diseases in the spring and summer
      months.

PMID- 19753927
TI  - Prioritizing patient care in the physician-provider relationship.

PMID- 19753928
TI  - Who lives? (We all do now--but it wasn't always that way).

PMID- 19753929
TI  - Reform: looking at common wealth from a commonwealth.

PMID- 19753930
TI  - Lifeline education program helps patients see the value of access care.

PMID- 19753931
TI  - VA coordinator in the spotlight.

PMID- 19753932
TI  - Patient empowerment requires patient responsibility. A nephrologist's
      perspective.

PMID- 19753933
TI  - Helping nephrologists, staff understand DNR orders.
AB  - Traditionally, outpatient dialysis facilities have chosen to enact DNR policies
      at a local level with input by the practitioners at those facilities. Under the
      new CMS Conditions for Coverage, and most state laws, this is no longer an
      option. We continue to have significant growth in the ESRD patient population and
      one of the largest segments of that growth is amongst elderly individuals. From
      1996 to 2003, the number of octogenarians and nonagenarians nearly doubled to
      13,577. After accounting for population growth, this represented a 57% increase
      in the rate of dialysis initiation in this age group. Notably the one-year
      mortality for this segment of the dialysis population was 46% during this time
      period. So clearly, many of these patients and their proxies will be dealing with
      end-of-life issues as they are being introduced to outpatient dialysis. Having a
      consistent and implementable policy to deal with this will be critical for the
      modern dialysis facility to meet this need.

PMID- 19753934
TI  - Knowledge and participation of front-line dialysis facility staff in end-of-life
      discussions.
AB  - The Centers for Medicare & Medicaid Services' Form 2746, the Death Notification
      Form, was revised in 2004. In addition to questions inquiring about
      discontinuation of dialysis, the revised form includes questions about patient
      and family involvement in the decision to discontinue treatment, whether the
      patient had received hospice care, as well as a new Cause of Death item #104,
      "Withdrawal from dialysis/uremia" However Form 2746 offers no instructions or
      explanation on how to decide whether a death is attributable to withdrawal from
      dialysis/uremia or what is considered dialysis discontinuation. We conducted a
      standardized telephone survey (N = 338) among front-line dialysis facility
      professionals (staff nurses, social workers, nurse managers) in ESRD Networks 1,
      5, and 12, inquiring about 448 deaths of patients who discontinued dialysis. Only
      70% of front-line staff reported Form 2746 was clear on when to indicate dialysis
      discontinuation, and only 57% reported it was clear when to use the death code
      #104 for withdrawal/uremia. According to facility staff, 49% of patients in the
      study group actively participated in the decision to discontinue dialysis.
      However only 8% of staff were aware of the patient's decision to discontinue
      dialysis by actually participating in the decision. Front-line staff knew that
      43% of patients in the study discussed end of life issues prospectively, but only
      57% of patients involved in discussions about dialysis discontinuation had
      interaction with physicians, according to the staff. We also found regional
      variations in dialysis discontinuation between the three Networks that
      participated in the study. This data indicates a lack of discussions about end of
      life issues with patients, even when they do occur, and sparse communication
      about the occurrence of these discussions with front-line staff. The study
      committee consisting of experienced nephrologists in kidney disease care and
      experts in end of life/palliative care who provided definitions for
      discontinuation and withdrawal from dialysis. Dialysis facilities should identify
      patients that have a greater probability of discontinuation. Front-line dialysis
      facility staff such as nurses and social workers should be aware of end of life
      discussions of their patients. Dialysis facilities should also have a process in
      place for end of life discussions that involves the interdisciplinary team, as
      suggested in the recently revised Conditions for Coverage for Participation for
      dialysis facilities.

PMID- 19753935
TI  - The evolution of nephrology guidelines: calling for a mid-course adjustment.

PMID- 19753936
TI  - Guidelines in nephrology: a new era of stimulating best care and best science.

PMID- 19753937
TI  - Maternal-child-reproductive health.

PMID- 19753938
TI  - USPHS Commissioned Corps: a global emergency preparedness and response asset.

PMID- 19753939
TI  - Incorporating rapid HIV testing into partner counseling and referral services.

PMID- 19753940
TI  - Redefining the mission: the Mercy Model as a leadership approach for public
      health systems and population-based programs.

PMID- 19753941
TI  - Reducing exposure to environmental toxicants before birth: moving from risk
      perception to risk reduction.
AB  - In this study, we considered approaches to reducing maternal exposure to
      hazardous environmental toxicants, focusing on risk communication to pregnant
      women and providers, but also considering identification of environmental
      toxicants in the community and reduction of environmental toxicants. We addressed
      the following questions: (1) What do pregnant women and their providers know
      about environmental toxicants and perinatal health? and (2) What policy
      strategies are needed (should be considered) to move forward in risk reduction in
      this area? We reviewed the literature on knowledge of pregnant women and
      providers regarding these issues. While there is limited research on what
      pregnant women and their providers know about environmental toxicants and
      perinatal health, there is evidence of reproductive and perinatal toxicity. This
      article describes a wide range of policy strategies that could be implemented to
      address environmental toxicants in the context of perinatal health. Effective
      leadership in this area will likely require collaboration of both environmental
      health and maternal and child health leaders and organizations.

PMID- 19753942
TI  - Determining accurate vaccination coverage rates for adolescents: the National
      Immunization Survey-Teen 2006.
AB  - Since 1994, the Centers for Disease Control and Prevention has funded the
      National Immunization Survey (NIS), a large telephone survey used to estimate
      vaccination coverage of U.S. children aged 19-35 months. The NIS is a two-phase
      survey that obtains vaccination receipt information from a random-digit-dialed
      survey, designed to identify households with eligible children, followed by a
      provider record check, which obtains provider-reported vaccination histories for
      eligible children. In 2006, the survey was expanded for the first time to include
      a national sample of adolescents aged 13-17 years, called the NIS-Teen. This
      article summarizes the methodology used in the NIS-Teen. In 2008, the NIS-Teen
      was expanded to collect state-specific and national-level data to determine
      vaccination coverage estimates. This survey provides valuable information to
      guide immunization programs for adolescents.

PMID- 19753943
TI  - Challenges and priorities for surveillance of stillbirths: a report on two
      workshops.
AB  - Stillbirths, those with and without birth defects, are an important public health
      topic. The National Center on Birth Defects and Developmental Disabilities at the
      Centers for Disease Control and Prevention conducted two workshops during April
      and July 2005. Both workshops explored the challenges of conducting surveillance
      of stillbirths. Workshop participants considered an approach that added the
      surveillance of stillbirths, those with and without birth defects, as part of
      existing population-based birth defects surveillance programs in Iowa and
      Atlanta. The workshops addressed three key aspects for expanding birth defects
      programs to conduct active, population-based surveillance on stillbirths: (1)
      case identification and ascertainment, (2) data collection, and (3) data use and
      project evaluation. Participants included experts in pediatrics, obstetrics,
      epidemiology, maternal-fetal medicine, perinatology and pediatric pathology,
      midwifery, as well as practicing clinicians and pathologists. Expanding existing
      birth defects surveillance programs to include information of stillbirths could
      potentially enhance the data available on fetal death reports and also could
      benefit such programs by improving the ascertainment of birth defects.

PMID- 19753944
TI  - Distributing free fresh fruit and vegetables at school: results of a pilot
      outcome evaluation.
AB  - OBJECTIVES: Consumption of fruit and vegetables among children is generally below
      recommended levels. This evaluation addressed two questions: (1) To what extent
      did children's attitudes toward, familiarity with, and preferences for fruit and
      vegetables change during the school year? and (2) To what extent did children's
      consumption of fruit and vegetables change during the school year? METHODS:
      During the 2004-2005 school year, the Mississippi Department of Education, Child
      Nutrition Programs initiated a pilot program to distribute free fruit and
      vegetables to students (kindergarten through 12th grade) during the school day.
      Data were collected in 2004-2005 within a one-group pretest/posttest design using
      a self-report questionnaire (n=725) and 24-hour dietary recalls (n=207) with a
      sample of students from five schools in Mississippi. Data were analyzed in 2006
      2007. RESULTS: Results showed greater familiarity with fruit and vegetables at
      all grade levels (p<0.05) and increased preferences for fruit among eighth- and
      10th-grade students (p<0.01). Eighth-grade students also reported more positive
      attitudes toward eating fruit and vegetables (p<0.01), increased perceived self
      efficacy to eat more fruit (p<0.01), and increased willingness to try new fruit.
      Finally, results showed increased consumption of fruit, but not vegetables, among
      eighth- and 10th-grade students (p<0.001). CONCLUSIONS: Distributing free fruit
      and vegetables at school may be a viable component of a more comprehensive
      approach for improving students' nutrition attitudes and behaviors. More program
      emphasis is needed on ways to promote vegetable consumption.

PMID- 19753945
TI  - The challenge of infant mortality: have we reached a plateau?
AB  - OBJECTIVES: Infant mortality is a major indicator of the health of a nation. We
      analyzed recent patterns and trends in U.S. infant mortality, with an emphasis on
      two of the greatest challenges: (1) persistent racial and ethnic disparities and
      (2) the impact of preterm and low birthweight delivery. METHODS: Data from the
      national linked birth/infant death datasets were used to compute infant mortality
      rates per 100,000 live births by cause of death (COD), and per 1,000 live births
      for all other variables. Infant mortality rates and other measures of infant
      health were analyzed and compared. Leading and preterm-related CODs, and
      international comparisons of infant mortality rates were also examined. RESULTS:
      Despite the rapid decline in infant mortality during the 20th century, the U.S.
      infant mortality rate did not decline from 2000 to 2005, and declined only
      marginally in 2006. Racial and ethnic disparities in infant mortality have
      persisted and increased, as have the percentages of preterm and low birthweight
      deliveries. After decades of improvement, the infant mortality rate for very low
      birthweight infants remained unchanged from 2000 to 2005. Infant mortality rates
      from congenital malformations and sudden infant death syndrome declined; however,
      rates for preterm-related CODs increased. The U.S. international ranking in
      infant mortality fell from 12th place in 1960 to 30th place in 2005. CONCLUSIONS:
      Infant mortality is a complex and multifactorial problem that has proved
      resistant to intervention efforts. Continued increases in preterm and low
      birthweight delivery present major challenges to further improvement in the
      infant mortality rate.

PMID- 19753946
TI  - Improvements in access to care for vulnerable children in California between 2001
      and 2005.
AB  - OBJECTIVE: We examined population changes in access to care for children in
      California during a period of major efforts to improve access to care for
      children. METHODS: We used cross-sectional data on 36,010 children aged 0-19
      years from the 2001 and 2005 California Health Interview Survey to assess
      population changes in access to care. We assessed changes in access by individual
      risk factors and a composite risk profile. RESULTS: In 2005, a smaller proportion
      of children were uninsured (8.2% vs. 10.9% in 2001), living in poverty (20.7% vs.
      23.2% in 2001), and in families without a high school education (20.8% vs. 23.6%
      in 2001), all p<0.001. Before and after adjusting for these changes in risk,
      children were more likely in 2005 to have had a physician visit (odds ratio [OR]
      = 1.09, 95% confidence interval [CI] 1.07, 1.12) and dental visit (OR=1.11, 95%
      CI 1.08, 1.14). Children were slightly less likely in 2005 to have a regular
      source of care (OR=0.94, CI 0.91, 0.96). Children who had the highest risk
      profiles (> or = 4 risk factors) experienced the largest gains in access. For
      example, children with three and > or = 4 risk factors had gains in dental visits
      of 11 and 20 percentage points, respectively (p<0.001 for each), compared with <
      or = 3 percentage points for children with fewer risk factors. CONCLUSIONS: This
      study found improvements in physician and dental visits between 2001 and 2005
      that were not fully explained by changes in insurance coverage or other
      demographic risk factors. Vulnerable children fared well during this period,
      suggesting that California may be making important and potentially replicable
      strides in reducing disparities.

PMID- 19753947
TI  - Time trends and seasonal patterns of health-related quality of life among U.S.
      adults.
AB  - OBJECTIVES: Although numerous studies have examined health-related quality of
      life (HRQOL) longitudinally, little is known about the impact of seasonality on
      HRQOL. We examined trend and seasonal variations of population HRQOL. METHODS: We
      used data from the monthly Behavioral Risk Factor Surveillance System (BRFSS). We
      examined monthly observed mean physically and mentally unhealthy days from
      January 1993 to December 2006, using the structural time-series model to estimate
      the trend and seasonality of HRQOL. RESULTS: We found overall worsening physical
      and mental health during the time period and a significant and regular seasonal
      pattern in both physical and mental health. The worst physical health was during
      the winter and the best physical health was during the summer. The mean number of
      physically unhealthy days in January was 0.63 days higher than in July. The worst
      mental health occurred during the spring and fall, but the magnitude of the
      seasonal effect was much smaller. The difference between the best and worst
      months of mentally unhealthy days was approximately 0.23 days. We found
      significant differences in unadjusted and season-adjusted unhealthy days in many
      counties. CONCLUSIONS: Our findings can be used to examine time-varying causal
      factors and the impact of interventions, such as policies designed to improve
      population health. Our findings also demonstrated the need for calculating season
      adjusted HRQOL scores when examining cross-sectional factors on the population
      HRQOL measures for continuous surveys or longitudinal data.

PMID- 19753948
TI  - Self-reported diabetes in Hispanic subgroup, non-Hispanic black, and non-Hispanic
      white populations: National Health Interview Survey, 1997-2005.
AB  - OBJECTIVES: We estimated the prevalence of self-reported diabetes in Hispanic
      subgroup (Puerto Rican, Mexican, Mexican American, Cuban, Dominican, Central and
      South American, and other Hispanic), non-Hispanic black, and non-Hispanic white
      populations aged 20 years and older. METHODS: Using the National Health Interview
      Survey 1997-2005, we limited these analyses to 272,041 records of adults aged 20
      years and older, including 46,749 records for Hispanic respondents. We used
      logistic regression to assess the strength of the association between
      race/ethnicity and self-reported diabetes before and after adjusting for selected
      characteristics. RESULTS: Compared with non-Hispanic white respondents, Mexican
      American (odds ratio [OR] = 2.02; 95% confidence interval [CI] 1.75, 2.34),
      Mexican (OR=1.52; 95% CI 1.31, 1.91), Puerto Rican (OR=1.53; 95% CI 1.23, 1.91),
      other Hispanic (OR=2.08; 95% CI 1.68, 2.58), and non-Hispanic black (OR=1.47; 95%
      CI 1.35, 1.61) respondents had greater odds of reporting diabetes. When compared
      with non-Hispanic white respondents, Mexican American respondents with less than
      a high school diploma had the lowest odds of reporting diabetes, while those with
      at least a college degree had greater odds of reporting diabetes. However, Puerto
      Rican respondents with less than a high school education, Mexican respondents
      with at least some college education, and other Hispanic respondents with at
      least a high school diploma/general equivalency diploma had greater odds of
      reporting diabetes. CONCLUSIONS: Although Hispanic respondents bear a greater
      burden of diabetes than non-Hispanic white respondents, this burden is unevenly
      distributed across subgroups. These findings call attention to data
      disaggregation whenever possible for U.S. racial/ethnic populations classified
      under categories considered homogeneous.

PMID- 19753949
TI  - Excess Hispanic fetal-infant mortality in a midwestern community.
AB  - OBJECTIVE: We assessed excess fetal-infant mortality for Hispanic, non-Hispanic
      white, and non-Hispanic black populations in five contiguous counties of Missouri
      and Kansas. METHODS: We conducted a perinatal periods of risk (PPOR) assessment
      of fetal-infant mortality using electronic linked birth-death record files from
      2001 through 2005. We generated an internal reference group in accordance with
      established PPOR protocol. We used Kitagawa analysis to determine whether excess
      deaths were due to birthweight distribution (a higher frequency of prematurity or
      growth retardation) or to higher mortality rates once born at that birthweight
      (birthweight-specific mortality). RESULTS: We found the excess fetal-infant death
      rates for Hispanic and non-Hispanic white populations to be similar and
      considerably lower than that for non-Hispanic black populations. Among Hispanic
      children, we judged 21.6% of fetal-infant mortality to be excess in relation to
      the reference population. Within the PPOR matrix, Hispanic excess mortality rates
      were distributed differently from those of non-Hispanic white and non-Hispanic
      black populations. Among Hispanic children, 93.6% of the excess mortality could
      be explained by low birthweight and birthweight-specific mortality, with the
      greatest contribution attributable to low birthweight. CONCLUSION: The excess
      fetal-infant mortality experience of Hispanic people in the five-county region
      was similar to that of the non-Hispanic white population, but was distributed
      differently in the PPOR model, which has significance regarding interventions
      targeting reductions in fetal-infant mortality.

PMID- 19753950
TI  - Lack of follow-up of prostate-specific antigen test results.
AB  - OBJECTIVES: We obtained population estimates of the prevalence of lack of
      diagnostic follow-up after an abnormal prostate-specific antigen (PSA) result and
      assessed the role of sociodemographic, access, and risk perception factors on
      follow-up of abnormal tests. METHODS: We used data from the 2000 National Health
      Interview Survey cancer control supplement. For 3,310 men aged 40 or older with a
      PSA test, 463 men reported an abnormal PSA test. Outcomes were abnormal PSA and
      lack of diagnostic follow-up in the latter group. Covariates for logistic
      regression included sociodemographic variables (age, race/ethnicity, and
      education), access to care (health insurance and usual source), and risk of
      cancer (family history and perceived risk). Survey analysis procedures accounted
      for the complex survey design. RESULTS: Abnormal PSA results were associated with
      age, family history, and perceived risk of cancer. Approximately 15% of men with
      abnormal PSA tests reported no follow-up. The estimated number was 423,549 (95%
      confidence interval [CI] 317,755, 529,343). No follow-up was more likely in
      Hispanic men (odds ratio [OR] = 2.21, 95% CI 1.04, 4.70) and men without
      insurance (OR=6.56, 95% CI 2.02, 21.29), but less likely in men with a family
      history of prostate cancer or higher perceived risk of cancer. CONCLUSIONS:
      Substantial numbers of men had no follow-up of abnormal PSA tests. Primary care
      physicians should assess continuity of care following abnormal PSA results. Data
      about prostate cancer screening and follow-up are needed to support clinical and
      policy decisions.

PMID- 19753951
TI  - The accuracy of a death certificate checkbox for diabetes: early results from New
      Jersey.
AB  - OBJECTIVES: The rapid growth in diabetes prevalence has increased interest in
      measuring the burden of this disease. One response has been to add a checkbox for
      diabetes status to the death certificate, which New Jersey did in 2004. This
      study assessed the accuracy of the diabetes checkbox and its effect on cause-of
      death coding. We analyzed whether a diabetes checkbox is a useful addition to the
      death certificate. METHODS: We examined the trend in cause-of-death coding for
      diabetes as an underlying and contributing cause of death by analyzing New Jersey
      mortality data between 1990 and 2005. We assessed the accuracy of the checkbox by
      examining inconsistencies between cause-of-death coding and checkbox status, and
      assessed sensitivity by analyzing linked hospital and death data for a cohort of
      decedents with diabetes. RESULTS: Between 2003 and 2005, there was approximately
      a 15% increase in the number of deaths listing diabetes as a contributing cause.
      The number of deaths where diabetes was listed as an underlying cause changed
      little. Approximately 10% of death certificates had an inconsistency between
      cause of death and checkbox status. The sensitivity analysis showed that
      approximately 40% of diabetic decedents had the appropriate checkbox status.
      CONCLUSION: The addition of the checkbox was accompanied by a change in the
      reporting of diabetes as a contributing cause of death. Results from the
      sensitivity analysis raise questions about the accuracy of the checkbox as a
      measure of the diabetic status of decedents.

PMID- 19753952
TI  - Family planning provider referral, facilitation behavior, and patient follow-up
      for abnormal Pap smears.
AB  - OBJECTIVES: Family planning (FP) clinics are important access points for cervical
      cancer screening and referrals for follow-up care for abnormal Papanicolaou (Pap)
      smears for a substantial number of U.S. women. Because little is known about
      referral and facilitation practices in these clinics or client action based on
      referrals, we sought to determine FP provider referral and facilitation practices
      when seeing FP clients with abnormal Pap smear results, and FP client follow-up
      for abnormal Pap smears due to FP provider referrals. METHODS: We conducted a
      mail survey of Medicaid-enrolled FP providers in Arkansas and Alabama, and
      conducted a telephone survey with a sample of FP clients of those providers
      responding to the provider survey. RESULTS: Major provider factors associated
      with referral included rural location, health department and clinic institutional
      setting, large Title X practice/clinic size, and high FP clinic focus. Major
      factors associated with facilitation included rural location, non-physician
      specialty, health department and clinic institutional setting, and small Title X
      clinic size. Of women reporting abnormal results, 62.4% reported follow-up care.
      Of those who received follow-up care, 40.0% received some care and a referral
      from their FP provider. A major factor associated with clients seeking follow-up
      care was being told by their FP provider where to go for follow-up care. Age was
      a major factor associated with clients actually obtaining follow-up care.
      CONCLUSIONS: Where follow-up care is not available at the FP site, referrals are
      critical and are a major factor associated with whether women seek care for the
      condition. Interventions to increase follow-up rates should focus on provider and
      system features, rather than clients.

PMID- 19753953
TI  - Evaluation of an outside-the-cold-chain vaccine delivery strategy in remote
      regions of western China.

PMID- 19753954
TI  - Silver bird: how the DC-3 contributed to public health in 1950s Nepal.

PMID- 19753955
TI  - District of Columbia v. Heller: implications for public health policy and
      practice.

PMID- 19753956
TI  - The Student Research Program at the University of South Florida College of Public
      Health: a valuable investment in graduate public health education.

PMID- 19753957
TI  - Passing health care reform legislation.

PMID- 19753958
TI  - Selling a medical practice 101.

PMID- 19753959
TI  - The ACS Case Log System: 2009 update.

PMID- 19753960
TI  - Health care reform: we all have a dog in this hunt.

PMID- 19753961
TI  - Amputee network provides peer support.

PMID- 19753962
TI  - Governor's Committee on Surgical Infections and Environmental Risks: an update.

PMID- 19753963
TI  - Governors' Committee on Physician Competency and Health: an update.

PMID- 19753964
TI  - Preparing for the switch to HIPAA 5010 and ICD-10-CM.

PMID- 19753965
TI  - Single-payor systems.

PMID- 19753966
TI  - Resident work hour restrictions.

PMID- 19753967
TI  - [Diagnosis and treatment for cervicothoracic junction injuries].

PMID- 19753968
TI  - [Application of the pedicle screws for cervicothoracic fracture-dislocation].
AB  - OBJECTIVE: To explore pedicle screw implantation for fracture-dislocation
      injuries at cervicothoracic junction (C6-T2). METHODS: Pedicle screw implantation
      was used for twenty-six patients with cervicothoracic fracture-dislocation from
      May 2001 to Jan 2008. There were 17 males and 9 females with an average of 48.5
      years (range,20 to 75 years). Single posterior pedicle screw fixation was
      performed for 17 cases, and posterior screw fixation combined with anterior
      reduction and plate fixation for the other nine. The accuracy of the pedicle
      screws were evaluated by CT views after surgery. Complications and neurological
      recovery were also recorded after the procedures. RESULTS: All subjects were
      followed up from 3 to 74 months with average 36.5 months. Four cases of complete
      paraplegia died of cardiovascular or pulmonary failure within half a year after
      surgery. There were 104 pedicle screws implanted totallythe including 74 pedicle
      screws in cervical vertebrae, 16 at C5, 16 at C6, 42 at C7, and 30 pedicle screws
      in upper thoracic vertebrae,in which 22 at T1, 8 at T2. No injury of spinal cord,
      nerve roots and vertebral artery was found during operation. Eleven screws
      (14.9%) were perforated out of the pedicles in cervical spine, in which 7(9.5%)
      through lateral cortex, 1 (1.4%) through the superior and 3 (4.1%) through the
      inferior. Three screws (10%) were perforated in upper thoracic spine, in which 2
      (6.7%) by lateral cortex and 1(3.3%) by the medial (within 2 mm). Bony fusion was
      achieved for all cases and all internal fixator was good except 1 screw broken at
      C5. JOA score increased from preoperative (7.5 +/- 2.0) to postoperative (14.5 +/
      2.3) evaluated in 6 months after operation,with statistic difference (t = 6.34,
      P < 0.05). Neurological improvement was gotten in all patients according to ASIA
      classification but three cases who suffered from complete neurological injuries.
      CONCLUSION: Implantation of pedicle screws at cervicothoracic junction can be
      safe and reliable if the urgeonis familiar with the local anatomy of
      cervicothoracic spine, and the technique for implantation of the screws. Related
      radiological parameters should be measured for each subject before the operation
      in attempt to get a therapy individually.

PMID- 19753969
TI  - [Treatment of traumatic intervertebrae disk herniation in cervical thoracic
      junction through transforminal approach].
AB  - OBJECTIVE: To investigate the treatment for traumatic intervertebrae disk
      herniation in cervical thoracic junction. METHODS: From 2003 to 2008, there were
      10 patients with trautimatic intervertebral disk herniation in cervical thoracic
      junction, which included 6 males and 4 females, aged from 23 to 66 years (means
      41.5 years). All of them were performed through the transforminal approach
      combined with internal fixation. After operation all patient underwent hyperbaric
      oxygen treatment. The function of spine was evaluated by JOA score system.
      RESULTS: All patients were followed up for 8 to 16 months(means 13 months). All
      patients got recovery of spine function to some extent except one case with
      complete spine damaged. The JOA scores was improved from (8 +/- 3) before
      operation to (15 +/- 2) after operation. CONCLUSION: Early and effective
      treatment by transforminal operation could be helpful for the recovery of spine
      function.

PMID- 19753970
TI  - [Treatment of conumminuted fractures of distal radius with percutaneous
      transfixation-pin fixation combined external fixator].

PMID- 19753971
TI  - [Diagnosis and treatment of cervicothoracic spinal fractures and dislocations in
      patients with ankylosing spondylitis].
AB  - OBJECTIVE: To discuss the pathological and clinical characteristics,methods of
      therapies and perioperative considerations of cervicothoracic spinal fractures
      and dislocations in patients with ankylosing spondylitis (AS). METHODS: Thirteen
      patients with ankylosing spondylitis and cervicothoracic spinal fractures and
      dislocations were treated from January 2001 to March 2009, including 11 males and
      2 females,aged varied from 33 to 60 years (mean 46) in 11 males and from 36 to 59
      years (mean 47.5) in 2 females respectively. The symptom duration of AS was from
      12 to 27 years (means 14.5 years). The chief complains were pain around cervical
      part and shoulder blades, some accompanied with decrease of motor power and
      sensation in upper or lower limbs. Spine radiographs revealed a displaced
      fracture of cervicothoracic spine. Laboratory examination presented positive
      results of HLA-B27 test. Fusion of fracture and ASIA neurological function grade
      variation were observed. RESULT: A total of 13 patients, who underwent operation,
      were followed up for 12 to 43 months(means 35.6 months). There were 6 patients
      were treated with anterior cervical discectomy and fusion, 4 with anterior
      cervical corpectomy and fusion, 1 with laminectomy and fusion and 2 with combined
      anterior and posterior stabilisation. The bone fusion were observed after
      reduction of fractures and dislocations ultimately. Twelve patients acquired an
      improved neurological status in different degrees, and only one suffered from
      persistent neurological impairment loss. The complications occurred in 5 cases
      during perioperation. CONCLUSION: This study suggests that most cervicothoracic
      spinal fractures and dislocations in patients with AS are extremely unstable and
      require operations. If operative method is proper and operative process accurate,
      either anterior,posterior or combined approach can achieve good spinal myeloid
      functional recovery with low rates of operative complications occurrence, under
      the guidence of imaging manifestation.

PMID- 19753972
TI  - [Characteristic and surgical treatment of cervicothoracic spine fracture].
AB  - OBJECTIVE: To discuss the clinical characteristic and surgical treatment of
      cervicothoracic spine fracture complicated with spine cord injury. METHODS:
      Thirty-eight patients with cervicothoracic fracture and spine cord injury were
      retrospectively analyzed from January 1998 to January 2007. There were 29 males
      and 9 females with an average age of 36.4 years ranging from 18 to 58 years. All
      patient suffered from pain and limitation of motion on cervicothoracic junction.
      According to American Spinal Injury Association (ASIA) grades, 4 cases were in
      grade A, 13 cases in grade B, 10 cases in grade C, 7 cases in grade D and 4 cases
      in grade E. All patients were treated with anterior decompressed, bone graft and
      Zephir plate fixation in cervicothoracic spine. RESULTS: All patients were
      followed up for 1 to 10 years, the mean followed up time was 4.5 years. And all
      patients got complete bone fusion within 4 to 6 months postoperatively. There
      were no pull-out and breakage of screws or plates. Spinal cord functional
      recovery improved on average 3.8 degree according AISA standard. Two patients
      appeared transient hoarse voice after surgery, the symptoms were alleviated from
      3 to 6 months after operation. Seven patients were complicated with Horner
      syndrome preoperatively, and the symptoms were disappeared after operation.
      CONCLUSION: The clinical situation of cervicothoracic spine fracture with spine
      cord injury is complicated. And anterior decompressed, bone graft and internal
      fixation performed on cervicothoracic spine fracture can achieve an efficient and
      safe clinical outcome.

PMID- 19753973
TI  - [Operating treatment for fracture and dislocation of lower cervical spine with
      articular process interlocking].
AB  - OBJECTIVE: To study the operative methods for fracture and dislocation of lower
      cervical spine with articular process interlocking. METHODS: From Feb. 2002 to
      Feb. 2008, 57 patients with fracture and dislocation of the lower cervical spine
      with articular process interlocking were treated by operation involving interior,
      posterior and combining anterior and posterior approach, of whom there were 45
      males and 12 females aged from 18 to 73 years old with average of 39.5 years.
      There were 35 patients caused by traffic accident, 17 patients by falling injury
      and 5 patienst by crash injury of heavy object. Injured cervical segment: there
      were 4 patienst with C3-C4, 13 patients with C4-C5, 32 patientst with C5-C6 and 8
      patients with C6-C7. Fracture types of cervical dislocation: there were 32
      patients with unilateral articular interlocking and 25 patients with bilateral
      articular interlocking. According to ASIA criteria the level of nerve injury was
      grade A in 9 patients,grade B in 17 patients, grade C in 19 patients and grade D
      in 12 patients. OPERATIVE METHODS: 14 patients were selected by anterior
      operation, 11 by posterior operation,and 32 by combining anterior and posterior
      operation. RESULTS: All patients were followed up for 3 to 26 months averaged 11
      months. According to ASIA criteria, all patients improved 1 to 2 grade. Patients
      with cervical fracture and dislocation recovered completely with normal cervical
      sequence and cervical curvature. There was no patients with cervical unstability.
      Bony fusion were found in the patients with anterior interbody fusion at 12 weeks
      after operation. CONCLUSION: The anterior operation was selected when one segment
      fractures on fresh and dislocation, or the cervical fracture and dislocation were
      reduction with traction, or the angulation deformity was severe. The posterior
      operation was selected when the cervical vertebral plate of articular facet
      fractures and the compression were from posterior, or multi-segment of cervical
      injured. The combining anterior and posterior operation was selected when the
      compression of spinal cord was from both side.

PMID- 19753974
TI  - [Therapeutic strategies in the surgical treatment of Hangman's fractures].
AB  - Hangman's fractures are located in the region between facets of the axis, which
      are accompanied by an increasing rate recently. However,there are no uniform
      standards for the treatment, especially for the treatment of fractures of types
      II and IIa because the operative approaches which include anterior and posterior
      are supported by different groups. The article tried to make an analysis on
      pathological anatomy, mechanism, types and surgical treatment of Hangman's
      fractures.

PMID- 19753975
TI  - [Repair of medical collateral ligament ruptures of the knee with suture anchor].

PMID- 19753976
TI  - [Comparison of two techniques of the transarticular screw placement in the lower
      cervical spine].
AB  - OBJECTIVE: To compare two techniques of the transarticular screw placement in the
      lower cervical spine, and to suggest and confirm a new technique of the
      placement. METHODS: The techniques of transarticular screw placements used by
      Takayasu (group A) and Dalcanto (group B) were applied in eight cervical
      specimens. The splits of facets,the encroachment of the cervical nerve roots and
      transverse foramens were observed and analyzed. The numbers of transarticular
      screws which not gone through the facets were counted in both group A and B,
      respectively. RESULTS: Sixty-four transarticular screws were implanted,thirty-two
      for group A, the same for group B. Although no splits of the facets were seen in
      group A, two transarticular screws did not go through the facets. There were ten
      splits of facets in group B, in which seven involved the inferior border of the
      inferior facets and three for the lateral border. No superior facets were found
      to be broken both in group A and B. Eight screws encroached the transverse
      foramens in group A and none in group B. Eleven of anterior branch and eight of
      posterior branch of lower cervical nerve roots were involved in group A, two and
      nine respectively in group B. CONCLUSION: There are high risk of injury of
      anterior branch of cervical nerve root and vertebral artery if the screws are too
      long and the Takayasu's technique is used. However, the rate of facet split is
      high if the Dalcanto's technique is applied.

PMID- 19753977
TI  - [Comparison of accuracy of pedicle screw placement in the thoracic spine using
      funnel technique and free hand technique].
AB  - OBJECTIVE: To study the accuracy the pedicle screw placement in the thoracic
      spine using funnel technique and free hand technique. METHODS: Eight cadavers
      including 5 males and 3 females were analysed. The age ranged from 57 to 82 years
      (mean 68 years). Cadawers were randomly assigned to one of two instrumentation
      groups. In four cadavers, "funnel technique" was used for screw placement. In the
      remaining four cadavers,free hand technique then was used. Success of pedicle
      screw placement was judged by CT scan. The rate of success of two ways was
      compared using statistic analysis. RESULTS: Ninety-six screws were inserted by
      "funnel technique" and free hand technique respectively, 84 of "funnel technique"
      were successful, and 73 of free hand technique were successful. Significant
      differences were found between two ways (P < 0.05). Chanciness tresis occurred in
      "funnel technique" on 2 screws and free hand technique on 9 screws. There were
      significant differences in rates of chanciness tresis (P < 0.05). CONCLUSION:
      Funnel technique is simple, safe and cost-effective alternative to any other
      thchnique for pedicle screw placement in thoracic spine,funnel technique is able
      to reduce the chance of critical injury of nerve root and dura.

PMID- 19753978
TI  - [Effect on transforming growth factor-beta1 of glucocorticoid-induced avascular
      necrosis of femoral head in rats by treatment of activating blood circulation of
      Chinese herbal medicine].
AB  - OBJECTIVE: To establish rat models of Steroid-avascular necrosis of femoral head,
      observe the effects of activating blood circulation of chinese herbal medicine on
      genetic expression of transforming growth factor-beta1 (TGF-beta1). To interpret
      the mechanism of the effect on Steroid-avascular necrosis of femoral head by
      activating blood circulation,and offer a effective method to clinical. METHODS:
      Cleaner-40 SD rats,half males and half females, weight (200 +/- 20) g, were
      randomly divided into 2 groups: 4 rats were in common group and 36 rats were in
      medel group. The rats in medel group were administered with 24.5 mg/kg
      hydroxyprednisone twice a week peritoneal injection for 6 weeks induced to femur
      head necrosis. The rats in common group were through gluteus injection as
      control. There were 4 rats were killed in each group after 6 weeks, to be assure
      that the model were succed. All surplus rats were divided into treatment group
      and control group:the treatment group were administrated with activating blood
      circulation of Chinese herbal medicine 12.3 ml/kg per day,the control group were
      administrated with sodium chloride 12.3 ml/kg per day. Then, after 6 and 8 weeks,
      killed the animal and detected all indexes. RESULTS: (1) The expression of TGF
      beta by immunohistochemistry and image analysis: the expression of femoral head
      TGF-beta increased significantly in treatment group than in control group and two
      group had significant differences. (2) Serum levels of TGF-beta1: in the
      treatment group serum expression of TGF-beta1 increased,compared with the control
      group had significant difference (P < 0.01). (3) The femoral head local TGF-beta1
      mRNA transcription: treatment group in the first six weeks, expressed that the
      increase in the first eight weeks, expressed also reduced,and the control group
      in the first six weeks, expressed a decrease in the first eight weeks,was not
      detected to TGF-beta1 mRNA expression of difference between the two groups was
      significant (P < 0.01). TGF-beta1 mRNA in serum and the femoral head with local
      expression of TGF-beta1, in consistency. CONCLUSION: Rat abdominal cavity
      prednisolone acetate injection plus intermittent standing avascular necrosis
      modeling stability, good repeatability. Taohongsiwu through the promotion of
      hormone-ischemic necrosis of the femoral head rat model of TGF-beta1 mRNA
      transcription, and promote expression of TGF-beta1.

PMID- 19753979
TI  - [Expression of hypoxia inducible factor-1alpha in long bone development].
AB  - OBJECTIVE: To observe dynamically the development of fetal long bone and detect
      the expression and distribution of HIF-1alpha,to investigate the expression
      pattern and possible effects of hypoxia inducible factor-1alpha (HIF-1alpha) in
      fetal long bone development of mouse. METHODS: E12.5, E13.5, E14.5, E15.5, E16.5
      and E17.5 pregnant C57BL6 mice were sacrificed. After sacrifice, the embryos were
      delivered by caesarean section. The development of fetal long bone was
      dynamically observed by stereoscopic microscope, and the distributional
      expression of HIF-1alpha protein was detected by using method of
      immunohistochemistry. The expression of HIF-1alpha mRNA and osteoblast marker
      gene at various stage were also detected by using methods of reverse
      transcription-polymerase chain reaction (RT-PCR). RESULTS: The cartilaginous long
      bone began to form and joints outline arised at E13.5, then the primary
      ossification center was observed at E14.5, showing opaque ossification under
      stereoscopic microscope,and then the osteogenesis expanded and extended to both
      sides. Immunohistochemistry demonstrated lots of HIF-1alpha protein positive
      chondrcytes in the center of primary ossification at E14.5, then they decreased
      dramatically. HIF-1alpha mRNA expressed at high level from E13.5 to E15.5, and
      then decreased to low level. CONCLUSION: Fetal long bone development pattern
      appeared to be endochondral osteogenisis process, existing hypoxia
      microenviroment may increase HIF-1alpha mRNA expression and thus initiate the
      cascade of endochondral osteogenisis.

PMID- 19753980
TI  - [Application of monitoring phosphocreatine kinase continuously and dynamically in
      early diagnosis of compartment syndrome].
AB  - OBJECTIVE: To determine the efficacy of phosphocreatine kinase in the early
      diagnosis of compartment syndrome. METHODS: Forty patients with compartment
      syndrome of limbs were reviewed from 2005 to 2008 including 34 males and 6
      females with an average age of (37.03 +/- 13.02) years. Monitoring
      phosphocreatine kinase continuously and dynamically after injured 2, 24 hours, 1,
      2, 3 and 4 weeks later. The concentration of CK were measured by using Japanese
      Olympus automatic biochemistry analysator. The muscle preparations from affected
      extremity were taken after operation and 1, 2, 3 weeks later for biopsy. RESULTS:
      Two hours later after injury, the contents of CK increased sharply and the
      contents of CK were about 20 times more than the nomal. Twenty-four hours later,
      the contents of CK reached its maximum,the contents of CK were about 42 times
      more than the nomal. One week later, the contents of CK recovered to normal
      level. Pathological changes of muscle were irreversible. CONCLUSION: The change
      of the contents of CK can reflect the progression of disease objectively. If it
      increased sharply, the chance of compartment syndrome was high. Monitored it
      dynamicly and continuously can provide assistant for early diagnosis of
      compartment syndrome and evaluating pathogenetic condition.

PMID- 19753981
TI  - [Treatment of acromioclavicular dislocation with steel wire or clavicular hook
      plate].
AB  - OBJECTIVE: To investigate the operative method and effect of the treatment of
      acromioclavicular dislocation with steel wire or clavicular hook plate. METHODS:
      Sixty-seven patients were reviewed in the study. In group A 34 patients were
      treated with steel wire internal fixation including 24 males and 10 females with
      an average age of 31.2 years ranging from 18 to 52. In group B 33 patients were
      treated with clavicular hook plate internal fixation including 19 males and 14
      females with an average age of 30.9 years ranging from 19 to 50. Compared the
      time of operation and bleeding and postoperative complications between two
      groups. RESULTS: The time of operation was (48.90 +/- 36.56) min in groups A and
      (79.50 +/- 29.34) min in group B,the time of group A was shorter than that of
      group. The bleeding during operation was (49.70 +/- 52.36) ml in group A and
      (121.10 +/- 49.08) ml in group B, the bleeding of group A was less than that of
      group B. Only 1 case in group A occurenced fixation failing. CONCLUSION:
      Treatment of acromioclavicular dislocation with steel wire is a simple and small
      wounds and effective way.

PMID- 19753982
TI  - [Anatomical condyler plate plus entire fibular bone graft for the treatment of
      distal communited fractures of femur].

PMID- 19753983
TI  - [Imaging evaluation of the contribution of the deep circumflex iliac arterial
      vascularized iliac bone grafting to the reconstruction of blood supply of the
      femoral head].
AB  - OBJECTIVE: To evaluate the contribution of the deep circumflex iliac arterial
      vascularized iliac bone grafting to the reconstruction of the blood supply of the
      femoral head through the digital subtraction angiography (DSA) or computied
      tomographic scanning angiography (CTA) of the both deep circumflex iliac artery
      and ECT, MRI judgement. METHODS: Forty-five patients with the intracapsular
      fracture of femoral neck included 30 males and 15 females with an average age of
      36.5 years ranging from 16 to 50. The course was from 6 to 25 days(means 10.2
      days). There were 20 cases of sub-headfractures, 10 cases of head-neck, 15 cases
      of trans-neck. All patients were treated by 3 titanium alloy cannulated screws
      and deep circumflex iliac arterial vascularized iliac bone grafting. A follow-up
      for an average of 3 years and 6 months was performed. The engorging of the artery
      and reconstruction of the blood supply of the femoral head was viewed
      dynamicly,using digital subtraction angiography (DSA) or computied tomographic
      scanning angiography (CTA) of the both deep circumflex iliac artery and ECT, MRI
      judgement of the femoral head. RESULTS: Three weeks after operation, 38
      transferred arteries were engorging via DSA, 2 of 7 not via CTA, but engorging
      via DSA. One year later after operation, all arteries were engorging via DSA or
      CTA. ECT examination in 3, 6, 12 months after operation displayed nuclide
      enriching in the femoral head and distributing uniformity. The region of interest
      (ROI) ratios of the fractured head of femur to contralateral counterpart (D/N) in
      all cases > 1.0. The average D/N after 3 months was (2.12 +/- 0.21), (2.04 +/-
      0.14) after 6 months, (l1.71 +/- 0.11) after 12 months. There was statistical
      differation between D/N after 12 months and 3 or 6 months (P < 0.05), but not
      between 3 and 6 months (P > 0.05), and MRI examination in all cases no founded
      decreasing of the density and changing of the form of the femoral head.
      CONCLUSION: DSA, CTA, ECT, MRI confirmed that the deep circumflex iliac arterial
      vascularized iliac bone can provide effective blood supply and is profit to the
      reconstruction of the blood supply of the femoral head after the fracture of the
      femoral neck.

PMID- 19753984
TI  - [Alternatives of anterior and posterior approaches for cervical spondylotic
      myelopathy].
AB  - OBJECTIVE: To discuss on the effect of cervical spondylotic myelopathy before and
      after surgery and assess its indications and efficacy. METHODS: From June 2002 to
      June 2006, 125 patients with cervical spondylotic myelopathy were analyzed
      retrospectively involving 58 anterior routine and 67 posterior routine, of which
      71 cases of males, 54 cases of females, aged from 28 to 69 years (average 53.4
      years). The course was 0.5 to 48 months (means 14 months). According to JOA score
      system preoperative and postoperative nerve function were analyzed, summarized
      anterior and posterior cervical spine surgery. RESULTS: All patients were
      followed up for from 6 to 30 months (average of 18 months). According to JOA
      score criteria: anterior cervical surgery preoperative JOA score was (8.78 +/-
      2.43) points, postoperative JOA score was (14.68 +/- 2.37) points, the results
      were excellent in 40 cases, good in 10 cases, effective in 6. Posterior surgical
      group preoperative JOA score was (8.49 +/- 2.58) points, postoperative JOA score
      was (14.26 +/- 2.83) points, the results were excellent in 42 cases, good in 12
      cases, effective in 8. Invalid operation occurrenced in 6 cases included 2 of
      anterior, 4 of posterior. The postoperative symptoms had worsed in 1 case of
      posterior operation. The two groups had no statistical difference in efficacy,
      but there were differences statistically in the same approach comparing
      preoperative and postoperative. CONCLUSION: Both anterior and posterior
      approaches have fine effect to the treatment of cervical spondylotic myelopathy
      (CSM). But the selection of the indication is very important, the patients with
      the pressure from anterior, the short-level changes, and the main symptoms of
      pyramid trac compression, adopt anterior approach on principle. While the
      patients with the pressure of spinal cord from posterior, multilevel changes,
      main symptoms of sensory disturbances, and accompanied by cervical spine canal
      stenosis mainly is introduced posterior approach.

PMID- 19753985
TI  - [Calcaneus fractures and comparment syndromes of the foot].
AB  - OBJECTIVE: To observe the relation of calcaneus fractures and compartment
      syhdromes of the foot taken place. METHODS: From April 2003 to March 2008, there
      were 78 cases with calcaneus fracures involving 72 males and 6 females, aged from
      17 to 56 years (averaged 34.2 years). The intracompartment pressures of 54 feet
      with the severity swell were measured with the Whiteside's method. Among them, 8
      patients were final diagnosed the compartment syndromes of the foot. After
      incision decompression through the foot bottom wall,the whole foot swell fade
      away quickly. After 5 to 10 days the decompression incision were sutured.
      RESULTS: The 8 patients were followed up for from 7 to 12 months,kinesthetic
      sense of the whole foot was mormal. None of the cases occurrenced claw toes,
      instep contracture and stiffness of the toes, et al. CONCLUSION: Compartment
      syndromes of the foot general occurrences during 1 to 3 days after calcaneus
      fractures. Fractures of Sanders II-IV is easy to complicate compartment syndromes
      of the foot.

PMID- 19753986
TI  - [Analysis of success and failure in treatment of fractures in the median and
      lower segments of tibia and fibula by man].

PMID- 19753987
TI  - [Surgical treatment of tibia plateau fractures with external fixator and the
      locking plate].
AB  - OBJECTIVE: To observe the clinical effect of the treatment for complex fractures
      of the tibial plateau through the application of the external fixator and the
      locking plate. METHODS: From Feb. 2006 to Oct. 2008,12 patients with tibial
      plateau fractures were treated with external fixator and locking plate included 8
      males and 4 females with an average age of 38 years ranging from 23 to 59.
      According to Schatzker type, 7 cases were type V and 5 cases were type VI. Using
      an anteromedial incision and an anterolateral approach, the locking plate were
      fixed in the tibia lateral. The collapse and height lossing of tibial plateau was
      observed through X-ray film before and after operation. The function of knee
      joint was evaluated according to HSS scoring. RESULTS: These patients were
      followed up for 4 to 18 months (means 9.79 months). Eleven cases had bone primary
      union,and 1 delayed union. No deep phlebothrombosis and osteofascial compartment
      syndrome occurened. The average healing time was 3.1 months. Between the
      preoperative and postoperative X-ray film there were no second stage depression
      fracture of the tibial plateau,postoperative reduction loss and bad alignment.
      The range of knee flexion was 90 degrees to 110 degrees. The HSS knee functional
      scoring was(75.50 +/- 10.01)scores after operation and (21.50 +/- 11.68) scores
      before operation. CONCLUSION: The treatment with the external fixator and the
      locking plate for complex fractures of the tibial plateau could provid continuous
      stability of fixation,prevent the fracture from second stage displacement and the
      knee force line change, protect the soft-tissue around the knee, reduce the
      postoperative complications. The knee joint function is satisfied.

PMID- 19753988
TI  - [Surgical treatment and the fixator selection for Pilon fractures].
AB  - OBJECTIVE: To explore the internal fixation selection and the operative method of
      Pilon fracture. METHODS: From Aug. 2004 to Aug. 2007,there were 40 patients with
      Pilon fractures involving 30 males and 10 females. Thirty cases were closed
      fracture and 10 were open fracture. Seven patients were treated by emergency
      operation, 3 patients were debrided and suture at first. Twenty-three patients
      were treated with open reduction and internal fixation (ORIF),the other seventeen
      patients were treated with LC-DCP,reconstruct plate for fixation or screw,
      Kirschner wire combine screw for fixation. RESULTS: All patients were followed up
      for 6 to 32 months (means 19 months). The time of union of fracture was about 3
      to 5 months. The outcome was evaluated according to Baired-Jackson criteria, the
      results were excellent in 27 cases,good in 7, fair in 5, poor in 1. Seven cases
      were found the operative incision and wound surface difficult to heal,among them
      5 cases came from the emergency operation patients, 1 case was closed fracture
      patient. They were be healed by change of dressing or dermatoplasty or skin flap.
      CONCLUSION: It is the key factor of treatment for Pilon fractures to correct
      evaluate before operation and select correct operation time. It is also important
      to selected suitable internal fixation and good reduction.

PMID- 19753989
TI  - [Complications of surgical treatment for femoral intertrochanteric fractures
      using dynamic hip screw].
AB  - OBJECTIVE: To investigate the complications of surgical treatments for femoral
      intertrochateric fractures using dynamic hip screw (DHS). METHODS: From Jan. 2002
      to Dec. 2007, sixty-nine patients with intertrochanteric fractures were treated
      by dynamic hip screw fixation included 27 males and 42 females,with an average
      age of 72.9 years ranging from 53 to 96 years. According to Evans classification
      there were 10 cases in type I ,21 in type II, 22 in type III, and 16 in type IV,
      of which 51 patients (73.9%) suffered from systematic diseases preoperatively.
      RESULTS: Fifty-seven patients were followed up for 8 to 70 months (41 months on
      average). Four patients died, 17 cases occurrenced systematic complications
      postoperatively. Internal fixation related complications occurred in 12 patients.
      There were 8 cases with mechanical failure of DHS including 4 of screw loosen,3
      of cutting-out of device through femoral head and neck and 1 of plate breakage.
      Five patients had a coxa vara, and delayed union occurred in 4 patients.
      CONCLUSION: Unstable fracture pattern produced high percentage of mechanical
      failure. In such cases DHS should not be the first choice for treatment. The
      appropriate treatment should be in relation to pre-operative fracture stability
      and osteoporosis.

PMID- 19753990
TI  - [Clinical characteristics of hyponatremia after craniocerebral injuries in 36
      patients].

PMID- 19753991
TI  - [Pith decompression of the femoral head and allograft fibula grafting for
      treatment of avascular necrosis of femoral head].
AB  - OBJECTIVE: To investigate the clinical efficacy of the pith decompression of the
      femoral head and fibular allograft transplantation in the treatment of early
      stage avascular necrosis. METHODS: From January 2004 to November 2008, 32 hips of
      25 patients with avascular necrosis of femoral head of Ia-IIIb period were
      treated by the pith decompression of the femoral head and fibular allograft
      transplantation, hollow lag screw fixation, included 17 males and 8 females, aged
      from 20 to 55 years old (39.1 years on average). Preoperative pain was from 2 to
      14 months (means 5.5 months). All patients were applied on conventional X-ray
      films, MRI examination, Harris score. RESULTS: The patients were followed up for
      12 to 48 months (means 36.4 months). X-ray film showed 21 hips of 18 cases
      improved,6 hips of 4 cases unchanged, no collapse of articular surface, 3 hips of
      2 cases deterioration, 2 hips of 1 case failed. Preoperative Harris score was
      (77.0 +/- 8.0) and postoperative (90.6 +/- 2.5), there was a significant
      difference (t = 1.67, P < 0.05). CONCLUSION: Pith decompression of the femoral
      head and fibular allograft transplantation in the treatment of early stage
      avascular necrosis of femoral head has advantage of joint function in bed-ridden
      after a short time, quick recovery,clinical symptoms improved. Its short-term
      efficacy is certain but long-term efficacy is still need further observation.

PMID- 19753992
TI  - [Misdiagnosis of whiplash injury of cervical spinal cord].

PMID- 19753993
TI  - [Application of saturation of blood oxygen measuring of extremities end in
      diagnosis of the fascia compartment syndrome].

PMID- 19753994
TI  - [Diagnosis and treatment of rotator cuff injuries in elder patients].

PMID- 19753995
TI  - [Manipulative treatment for subluxation of capitulum radii in adult: 1 case
      report].

PMID- 19753996
TI  - [Treatment of child ultra-radius distal fracture of back to back with
      manipulative reduction and external fixation of splint and plaster].

PMID- 19753997
TI  - [Sleeve fractures of the patella in children: a case report].

PMID- 19753998
TI  - [Clinical observation on treatmen of cutaneous nerve entrapment syndrome of upper
      limb by Pizhen].

PMID- 19753999
TI  - [Overseas advance on the use of locking plates].
AB  - Locking plate technology offers improved fixation stability in osteopenic bone
      and for comminuted and periarticular fractures. The additional stability per
      screw compared with that of conventional nonlocking fixation enhances the
      application of minimally invasive fracture techniques. The application of locking
      plates is somewhat more difficult than the placement of conventional plates.
      Fracture reductions are often done indirectly, the locking screw must be
      carefully aligned along the axis of the receiving hole to ensure proper
      tightness, and the length of the plate must be selected carefully. The use of
      locking plates will likely increase, particularly with the increasing prevalence
      of osteopenic fractures on our aging population and the increase in high-energy
      fractures in younger patients severe trauma.

PMID- 19754000
TI  - Biological prognostic markers in chronic lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia (CLL) is the most frequent leukemic disease of
      adults in the Western world. It is remarkable by an extraordinary heterogeneity
      of clinical course with overall survival ranging from several months to more than
      15 years. Classical staging sytems by Rai and Binet, while readily available and
      useful for initial assessment of prognosis, are not able to determine individual
      patient's ongoing clinical course of CLL at the time of diagnosis, especially in
      early stages. Therefore, newer biological prognostic parameters are currently
      being clinically evaluated. Mutational status of variable region of
      immunoglobulin heavy chain genes (IgVH), cytogenetic aberrations, and both
      intracellular ZAP-70 and surface CD38 expression are recognized as parameters
      with established prognostic value. Molecules regulating the process of
      angiogenesis are also considered as promising markers. The purpose of this review
      is to summarize in detail the specific role of these prognostic factors in
      chronic lymphocytic leukemia.

PMID- 19754001
TI  - CC and CXC chemokines patterns in psoriasis determined by protein array method
      were influenced by Goeckerman's therapy.
AB  - Goeckerman's therapy (GT) of psoriasis is based on daily application of pharmacy
      grade coal tar on affected skin with subsequent exposure to UV light. The aim of
      this study was to evaluate the influence of Goeckerman's therapy of psoriasis on
      the levels of proangiogenic chemokines ENA-78 (CXCL5, Epithelial Cell Derived
      Neutrophil Attractant-78), GRO alpha (CXCL1, Growth-Related Oncogene), IL-8
      (CXCL8, Interleukin-8), MCP-1 (CCL2, Monocyte Chemotactic (Chemoattractant)
      Protein 1) and RANTES (CCL5, Regulated on Activation of Normal T Cell Expressed
      and Secreted) in peripheral blood of 22 children's patients with psoriasis. 22
      otherwise healthy children serve as a control group. The serum levels of
      chemokines were determined by commercial membrane protein array technique
      (RayBiotech, USA). Efficacy of Goeckerman's therapy was delineated by PASI score.
      Disease activity was significantly diminished by Goeckerman's therapy (p <
      0.001). Serum levels of GRO alpha and MCP-1 in patients before GT were
      significantly higher than those measured in healthy blood donors (GRO alpha: p =
      0.0128 and MCP-1: p = 0.0003). Serum levels of GRO alpha, MCP-1 and RANTES were
      significantly diminished by GT (GRO alpha: p = 0.002, MCP-1: p = 0.048 and
      RANTES: p = 0.0131). Compared to the healthy controls, serum level of MCP-1
      remained significantly increased in psoriasis patients after GT (p < 0.0001). In
      conclusion, we found that the GT of psoriasis influenced the serum levels of
      proinflammatory and proangiogenic chemokines, especially GRO alpha, MCP-1 and
      RANTES. It could be the cause for decreased proangiogenic activity which is
      described after GT of psoriasis.

PMID- 19754002
TI  - Mood stabilizer therapy and pravastatin: higher risk for adverse skin reactions?
AB  - We report on a serious side effect in a severely depressed 55-year-old woman, who
      presented an erythematous pigmented skin rash on the whole body under combination
      treatment with antidepressants, atypical antipsychotic drugs, the mood stabilizer
      lithium and the lipid-lowering drug pravastatin. The skin rash effect was most
      probably due, in first line, to olanzapine, but the cutaneous skin condition was
      triggered and aggravated by pravastatin, a 3-hydoxy-3-methylglutaryl-coenzyme A
      (HMG-CoA)-reductase inhibitor, and lithium medication. The allergic reaction
      started to develop after co-administration of pravastatin. Therefore, the
      combination of atypical antipsychotics with statins should be carefully monitored
      and the benefits and disadvantages should be balanced.

PMID- 19754003
TI  - Dural metastasis mimicking meningioma: an interesting case.
AB  - Dural metastasis is a rare entity in clinical practice. We report a case of dural
      metastasis secondary to thyroid carcinoma, which on both preoperative CT and MRI
      and at surgery had the typical appearance of a meningioma. Histopathological
      findings confirmed metastatic follicular thyroid carcinoma as a primary site.
      Although rare, dural metastases can mimic a meningioma. Our experience in this
      case has led us to consider metastasis as a differential diagnosis even when a
      meningioma is suspected. We believe that reporting of the case of dural
      metastasis mimicking a meningioma may help clinicians in future.

PMID- 19754004
TI  - Thoracic radiotherapy for mediastinal nodal recurrence.
AB  - Radiotherapy has been used to treat loco-regional recurrences located at various
      intra-thoracic sites, but long-term survival of these patients has been rarely
      observed. We report herein a lung adenocarcinoma patient with locoregional
      recurrence, who was successfully treated with high-dose radiotherapy. The patient
      could survive with no evidence of recurrence 5 years after thoracic irradiation.
      It is probably safe to administrate high-dose radiotherapy for some loco-regional
      recurrent patients with favorable prognostic factors such as good PS, no body
      weight loss. Further studies will be required to define a favorable subset of
      patients most likely to benefit from an aggressive approach.

PMID- 19754005
TI  - An assembly of anomalous extensor tendons of the hand--anatomical description and
      clinical relevance.
AB  - Innumerable descriptions about variations in the pattern of extensor tendons are
      recorded in the literature. The dorsum of the hand in an adult male cadaver
      revealed an unusual pattern of extensor arrangement during a gross anatomical
      practical session. The extensor digitorum, extensor indicis and extensor digiti
      minimi tendons displayed a variant pattern. Extensor digitorum contributed
      tendons only to the middle and ring fingers, with junctura tendinum present
      between the extensor digitorum for the ring finger and extensor digiti minimi.
      Interestingly, an accessory muscle was observed arising from the common extensor
      origin passing to the index finger, in addition to the usual extensor indicis.
      The origin and insertion of extensor digiti minimi was as usual with an accessory
      slip contributed from the extensor carpi ulnaris to the proximal phalanx of the
      fifth finger. The plethora of variations in this region is of paramount
      importance for the reconstructive surgeon, who may utilize the accessory tendons
      to restore functional capacity of the fingers.

PMID- 19754006
TI  - The effect of Hurricane Katrina: births in the U.S. Gulf Coast region, before and
      after the storm.
AB  - OBJECTIVES: This report presents birth data for the region affected by Hurricane
      Katrina, which made landfall along the Gulf Coast of the United States on August
      29, 2005, comparing the 12-month periods before and after the storm according to
      a wide variety of characteristics. Data are presented for maternal demographic
      characteristics including age, race, Hispanic origin, marital status, and
      educational attainment; medical care utilization by pregnant women (prenatal care
      and method of delivery); and infant characteristics or birth outcomes (period of
      gestation and birthweight). METHODS: Descriptive tabulations of data reported on
      the birth certificates of residents of the 91 Federal Emergency Management Agency
      (FEMA)-designated counties and parishes of Alabama, Louisiana, and Mississippi
      are presented for the 12-month periods before and after Hurricane Katrina struck,
      from August 29, 2004, through August 28, 2006. Detailed data are shown separately
      for 14 selected, FEMA-designated coastal counties and parishes within a 100-mile
      radius of the Hurricane Katrina storm path, the area hit very hard by the storm
      and subsequent flooding. These 14 selected coastal counties and parishes are a
      subset of the 91 FEMA-designated counties and parishes. RESULTS: The total number
      of births in the 14 selected FEMA-designated counties and parishes decreased 19
      percent in the 12 months after Hurricane Katrina compared with the 12 months
      before, with births declining in the selected counties and parishes of Louisiana
      and Mississippi and rising in the counties of Alabama. The number of births to
      non-Hispanic black women in the selected parishes of Louisiana fell substantially
      after Hurricane Katrina; births declined for non-Hispanic white, Hispanic, and
      Asian or Pacific Islander women in these selected parishes as well. The
      percentage of births to women under age 20 years for the selected counties and
      parishes after the storm was essentially unchanged in Alabama and Mississippi,
      but decreased in Louisiana. The proportion of births to unmarried women decreased
      in the selected parishes of Louisiana, but increased in the selected counties
      elsewhere. Large decreases were observed in very preterm and very low birthweight
      rates for the selected parishes of Louisiana following Hurricane Katrina, whereas
      a large increase was observed in very preterm births for the selected counties of
      Alabama.

PMID- 19754007
TI  - [The state of emergency medicine in Switzerland in 2009].

PMID- 19754008
TI  - [Indications for low-dose CT in the emergency setting].
AB  - CT delivers a large dose of radiation, especially in abdominal imaging. Recently,
      a low-dose abdominal CT protocol (low-dose CT) has been set-up in our
      institution. "Low-dose CT" is almost equivalent to a single standard abdominal
      radiograph in term of dose of radiation (about one sixth of those delivered by a
      standard CT). "Low-dose CT" is now used routinely in our emergency service in two
      main indications: patients with a suspicion of renal colic and those with right
      lower quadrant pain. It is obtained without intravenous contrast media. Oral
      contrast is given to patients with suspicion of appendicitis. "Low-dose CT" is
      used in the frame of well defined clinical algorithms, and does only replace
      standard CT when it can reach a comparable diagnostic quality.

PMID- 19754009
TI  - [Somatic and psychiatric emergencies: building a mutual view].
AB  - The prevalence of behavioural disorders is high among patients admitted to urban
      Accident and Emergency Departments. These disorders are not necessarily related
      to the reason for consultation and emergency physicians (EP) should be able to
      detect these patients and refer them to a psychiatrist when required. On the
      other hand, the frequent comorbid somatic disorders among patients attending an
      emergency psychiatric unit should raise concern from psychiatrists and prompt the
      need for EP advice. Due to the complex relationship between somatic and
      psychiatric disorders, a close collaboration between psychiatrists and EPs is
      crucial for efficient and patient care, as well as developing teaching and
      research.

PMID- 19754010
TI  - [Shock: diagnostic evaluation in the emergency department].
AB  - The identification of shock may be sometimes easy or on the other hand difficult
      due to the lack of accuracy of ancillary tests. The use of ultrasound has
      modified the initial emergency assessment of patients presenting with shock, in
      that it can now be used to differentiate between different types of shock
      (cardiogenic versus hypovolemic). The use, performance, and clinical benefits of
      ultrasound protocols applied by emergency physicians, still remain to be
      validated before to be implemented.

PMID- 19754011
TI  - [Carbon monoxide poisoning: an update for 2009].
AB  - Carbon monoxide (CO) is the leading cause of death by poisoning in developed
      countries. In 2006, 23 deaths and more than 130 hospitalisations related to CO
      poisoning have been reported in Switzerland. Impairment in oxygen transport
      through competitive antagonist action on hemoglobin is well known. Other
      mechanisms, in particular CO induced mitochondrial dysfunction, participate in CO
      toxicity. CO intoxications carry a high risk of immediate mortality and long-term
      neuropsychiatric or cardiac sequelae which justify the need of early diagnosis
      and treatment. Administration of supplemental oxygen is the cornerstone of
      treatment of CO poisoning. Hyperbaric oxygen therapy must be considered for the
      treatment of severe intoxications.

PMID- 19754012
TI  - [Scuba diving and hyperbaric medicine].
AB  - Scuba diving is widely practiced in Switzerland. Although rare, decompression
      sickness may be serious and require specialized treatment. Hyperbaric therapy has
      been used for a long time with beneficial effects on decompression sickness and
      gaseous embolism. Conversely, barotrauma does not require recompressive therapy.

PMID- 19754013
TI  - [Elective indication for hyperbaric oxygen therapy].
AB  - Creation of an hyperbaric medical center in Geneva allows development of elective
      indications of hyperbaric oxygen therapy. Physiologics effects of hyperbaric
      oxygen are well known, but credibles clinicals trials lacks. Frequents
      indications such as diabetic foot ulcer, ischemic ulcer or anaerobic infection
      will be rewieved here. Others indications will be summarize in a table with
      actual level of scientific proof. Hyperbaric oxygen therapy is always
      complementary to usual therapy and need numerous sessions to reach awaited
      results.

PMID- 19754014
TI  - [Echocardiography by emergency and intensive care physicians ].

PMID- 19754015
TI  - [Alternative physician reimbursement for basic insurance: a violation of the
      principal of religious neutrality?].

PMID- 19754016
TI  - [A new Camp David?].

PMID- 19754017
TI  - [Do we need to prohibit artificial tanning?].

PMID- 19754018
TI  - [BMI and longevity].

PMID- 19754019
TI  - [Transsexualism and genetic studies: is there a genetic basis for
      transsexualism?].

PMID- 19754020
TI  - [H1N1: future disturbing questions regarding vaccination].

PMID- 19754021
TI  - Transitional competency.

PMID- 19754022
TI  - Educating nurse planners: taking continuing nursing education on the talk show
      circuit.
AB  - Current American Nurses Credentialing Center accreditation criteria require that
      provider units have a process for educating and updating nurse planners. One
      provider unit's creative approach to meeting this key element is described here.

PMID- 19754023
TI  - Surviving cardiac arrest.
AB  - Surviving cardiac arrest requires high-quality cardiopulmonary resuscitation,
      advanced life support interventions, and optimal post-cardiac arrest care. After
      return of spontaneous circulation and stabilization of airway, breathing, and
      circulation, the focus shifts to the treatment of post-cardiac arrest syndrome.
      Research indicates this unique and complex syndrome requires specific treatment
      strategies.

PMID- 19754024
TI  - More situations in which questions are valuable.
AB  - This column discusses more situations in which questions are valuable.

PMID- 19754025
TI  - Building an extraordinary career in nursing: promise, momentum, and harvest.
AB  - The transition from nursing student to graduate nurse and beyond represents a
      challenging evolution. Although many resources are available to explain the
      career progression of new graduates and to help them with entry into the
      profession, fewer resources exist to assist nurses in planning a successful long
      term career trajectory. This article provides an overview of a developmental
      model for planning at various stages of career progression.

PMID- 19754027
TI  - The first year of practice: new graduate nurses' transition and learning needs.
AB  - Although the phenomenon of reality shock has been acknowledged as part of the new
      graduate nurse transition for decades, there is evidence to suggest that the
      problems with the transition into practice are more serious today. This article
      presents findings about the new graduate nurse transition and learning needs from
      qualitative research conducted in a community-based novice nurse transition
      program. The new graduate nurse transition and learning needs are examined
      through the eyes of new graduates and the nursing leaders and preceptors who work
      with them. Recommendations are offered for continuing education initiatives that
      can be designed to meet these needs.

PMID- 19754028
TI  - Progress meetings: facilitating role transition of the new graduate.
AB  - Although the very best orientation will not fully eliminate new graduates' sense
      of anxiety, a successful orientation will guide the novice registered nurse to
      use these feelings constructively by promoting a sense of confidence, competence,
      and satisfaction. This article provides details and examples of how progress
      meetings can be a beneficial addition to an orientation template. Progress
      meetings offer an avenue to facilitate social support and clinical growth
      supporting the transition from new graduate nurse to independent staff nurse.

PMID- 19754029
TI  - Retaining the next generation of nurses: the Wisconsin nurse residency program
      provides a continuum of support.
AB  - Because of the high costs associated with new graduate nurse turnover, an
      academic-service partnership developed a nurse residency program that provides a
      comprehensive support system that spans 15 months. Now in its fourth year,
      involving more than 50 urban and rural hospitals of varying sizes and geographic
      locations, the program provides formalized preceptor training, monthly daylong
      educational sessions, and mentoring by clinical coaches. Key factors contributing
      to the success of this program are a dedicated, cohesive planning team of
      individuals who embrace a common agenda, stakeholder buy-in, appropriate
      allocation of resources, and clear articulation of measures of success, with
      associated data collection. Successful elements of the monthly educational
      sessions are the use of interactive teaching methods, inclusion of content
      tailored to the unique needs of the nurse residents, and storytelling to
      facilitate learning from practice. Finally, training to advance the skill
      development of preceptors, coaches, educators, and facilitators has provided
      organizations with enduring benefits.

PMID- 19754030
TI  - Relationships of new nurses' perceptions and measured performance-based clinical
      competence.
AB  - BACKGROUND: This study examined the relationship between new nurses' performance
      based measurements and perceptions of clinical competence. METHODS: Descriptive
      correlational designs were used to examine the relationships. Performance-based
      clinical competence was measured by the Performance Based Development System
      developed by Del Bueno (1990), and perceived competence was measured by specific
      items on the Casey-Fink Graduate Nurse Experience Survey (1999). RESULTS:
      Findings showed a significant difference in mean patient scores and professional
      role scores. Nurses who met the criteria for problem management had significantly
      higher scores on the patient care scale and the professional role scale than
      those who did not meet the criteria. Nurses with previous work experience (44%)
      were more likely to meet the criteria for problem management. Black participants
      scored lower on the patient care scale compared with others. CONCLUSION: This
      study provides a beginning understanding of the relationship between new nurses'
      perceptions and performance-based clinical competence.

PMID- 19754031
TI  - Optimal parental care. Suggestions for children of aging parents.

PMID- 19754034
TI  - Story sharing an invaluable experience.

PMID- 19754035
TI  - CNE Quiz.

PMID- 19754036
TI  - Radiologic case study. Failed total knee arthroplasty with dislocated rotating
      platform polyethylene component.

PMID- 19754037
TI  - Putting Descartes before "dehorse".

PMID- 19754038
TI  - Laying floors--not much fun.

PMID- 19754039
TI  - "Zipper" molecular beacons: a generalized strategy to optimize the performance of
      activatable protease probes.
AB  - We report the proof-of-principle concept for zipper molecular beacons (ZMB)
      comprising an asymmetrical polyarginine/polyglutamate electrostatic "zipper"
      hairpin-linked fluorophore-quencher pair. The objective is to balance maximal
      quenching efficiency and optimal two-step activation (protease cleavage/zipper
      dissociation), while enhancing target cell uptake. This strategy also eliminates
      the peptide sequence dependence of conventional protease beacons. This ZMB
      concept is a generalizable approach to improve the functionality of a wide range
      of diagnostic/therapeutic probes through a simple switching of substrate
      sequences.

PMID- 19754040
TI  - Proteomic analysis reveals a synergistic mechanism of fluconazole and berberine
      against fluconazole-resistant Candida albicans: endogenous ROS augmentation.
AB  - Our previous study showed that concomitant use of berberine (BBR) and fluconazole
      (FLC) provided a synergistic action against FLC-resistant Candida albicans (C.
      albicans) clinical strains in vitro. To clarify the mechanism underlying this
      action, we performed a comparative proteomic study in untreated control cells and
      cells treated with FLC and/or BBR in 2 clinical strains of C. albicans resistant
      to FLC. Our analyses identified 16 differentially expressed proteins, most of
      which were related to energy metabolisms (e.g., Gap1, Adh1, and Aco1). Functional
      analyses revealed that FLC + BBR treatment increased mitochondrial membrane
      potential, decreased intracellular ATP level, inhibited ATP-synthase activity,
      and increased generation of endogenous reactive oxygen species (ROS) in FLC
      resistant strains. In addition, checkerboard microdilution assay showed that
      addition of antioxidant ascorbic acid or reduced glutathione reduced the
      synergistic antifungal activity of FLC + BBR significantly. These results suggest
      that mitochondrial aerobic respiration shift and endogenous ROS augmentation
      contribute to the synergistic action of FLC + BBR against FLC-resistant C.
      albicans.

PMID- 19754041
TI  - Kinetic and energetic paradigms for dye-sensitized solar cells: moving from the
      ideal to the real.
AB  - Dye-sensitized solar cells (DSSCs) are photoelectrochemical solar cells. Their
      function is based on photoinduced charge separation at a dye-sensitized interface
      between a nanocrystalline, mesoporous metal oxide electrode and a redox
      electrolyte. They have been the subject of substantial academic and commercial
      research over the last 20 years, motivated by their potential as a low-cost solar
      energy conversion technology. Substantial progress has been made in enhancing the
      efficiency, stability, and processability of this technology and, in particular,
      the interplay between these technology drivers. However, despite intense research
      efforts, our ability to identify predictive materials and structure/device
      function relationships and, thus, achieve the rational optimization of materials
      and device design, remains relatively limited. A key challenge in developing such
      predictive design tools is the chemical complexity of the device. DSSCs comprise
      distinct materials components, including metal oxide nanoparticles, a molecular
      sensitizer dye, and a redox electrolyte, all of which exhibit complex
      interactions with each other. In particular, the electrolyte alone is chemically
      complex, including not only a redox couple (almost always iodide/iodine) but also
      a range of additional additives found empirically to enhance device performance.
      These molecular solutes make up typically 20% of the electrolyte by volume. As
      with most molecular systems, they exhibit complex interactions with both
      themselves and the other device components (e.g., the sensitizer dye and the
      metal oxide). Moreover, these interactions can be modulated by solar irradiation
      and device operation. As such, understanding the function of these
      photoelectrochemical solar cells requires careful consideration of the chemical
      complexity and its impact upon device operation. In this Account, we focus on the
      process by which electrons injected into the nanocrystalline electrode are
      collected by the external electrical circuit in real devices under operating
      conditions. We first of all summarize device function, including the energetics
      and kinetics of the key processes, using an "idealized" description, which does
      not fully account for much of the chemical complexity of the system. We then go
      on to consider recent advances in our understanding of the impact of these
      complexities upon the efficiency of electron collection. These include
      "catalysis" of interfacial recombination losses by surface adsorption processes
      and the influence of device operating conditions upon the recombination rate
      constant and conduction band energy, both attributed to changes in the chemical
      composition of the interface. We go on to discuss appropriate methodologies for
      quantifying the efficiency of electron collection in devices under operation.
      Finally, we show that, by taking into account these advances in our understanding
      of the DSSC function, we are able to recreate the current/voltage curves of both
      efficient and degraded devices without any fitting parameters and, thus, gain
      significant insight into the determinants of DSSC performance.

PMID- 19754042
TI  - Predicted trends of core-shell preferences for 132 late transition-metal binary
      alloy nanoparticles.
AB  - Transition-metal alloyed nanoparticles with core-shell features (shell enrichment
      by one of the metals) are becoming ubiquitous, from (electro-)catalysis to
      biomedical applications, due to their size control, performance,
      biocompatibility, and cost. We investigate 132 binary-alloyed nanoparticle
      systems (groups 8 to 11 in the Periodic Table) using density functional theory
      (DFT) and systematically explore their segregation energies to determine core
      shell preferences. We find that core-shell preferences are generally described by
      two independent factors: (1) cohesive energy (related to vapor pressure) and (2)
      atomic size (quantified by the Wigner-Seitz radius), and the interplay between
      them. These independent factors are shown to provide general trends for the
      surface segregation preference for atoms in nanoparticles, as well as semi
      infinite surfaces, and give a simple correlation (a "design map") for the
      alloying and catalytic behavior. Finally, we provide a universal description of
      core-shell preference via tight-binding theory (band-energy differences) that (i)
      quantitatively reproduces the DFT segregation energies and (ii) confirms the
      electronic origins and correlations for core-shell behavior.

PMID- 19754043
TI  - A multicomponent coupling sequence for direct access to substituted quinolines.
AB  - A titanium-catalyzed three-component coupling reaction can be used to generate
      tautomers of N-aryl-1,3-diimines. Simple treatment of these products with acetic
      acid leads to cyclization forming quinoline derivatives in a one-pot procedure.
      The primary amines employed can be substituted anilines, aminonaphthalenes, or
      even heterocyclic amines, which leads to a variety of fused-ring heterocyclic
      frameworks. The one-pot yields varied from 25-71% for the 18 examples presented
      in this study.

PMID- 19754044
TI  - Solvent effects in chemical processes. water-assisted proton transfer reaction of
      pterin in aqueous environment.
AB  - Pterins are members of a family of heterocyclic compounds present in a wide
      variety of biological systems and may exist in two forms, corresponding to an
      acid and a basic tautomer. In this work, the proton transfer reaction between
      these tautomeric forms was investigated in the gas phase and in aqueous solution.
      In gas phase, the intramolecular mechanism was carried out for the isolated
      pterin by quantum mechanical second-order Moller-Plesset perturbation theory
      (MP2/aug-cc-pVDZ) calculations and it indicates that the acid form is more stable
      than the basic form by -1.4 kcal/mol with a barrier of 34.2 kcal/mol with respect
      to the basic form. In aqueous solution, the role of the water molecules in the
      proton transfer reaction was analyzed in two separated parts, the direct
      participation of one water molecule in the reaction path, called water-assisted
      mechanism, and the complementary participation of the aqueous solvation. The
      water-assisted mechanism was carried out for one pterin-water cluster by quantum
      mechanical calculations and it indicates that the acid form is still more stable
      by -3.3 kcal/mol with a drastic reduction of 70% of the barrier. The bulk
      solution effect on the intramolecular and water-assisted mechanisms was included
      by free energy perturbation implemented on Monte Carlo simulations. The bulk
      water effect is found to be substantial and decisive when the reaction path
      involves the water-assisted mechanism. In this case, the free energy barrier is
      only 6.7 kcal/mol and the calculated relative Gibbs free energy for the two
      tautomers is -11.2 kcal/mol. This value is used to calculate the pK(a) value of
      8.2 +/- 0.6 that is in excellent agreement with the experimental result of 7.9.

PMID- 19754046
TI  - Theoretical analysis of kinetic isotope effects on proton transfer reactions
      between substituted alpha-methoxystyrenes and substituted acetic acids.
AB  - Primary kinetic isotope effects (KIEs) on a series of carboxylic acid-catalyzed
      protonation reactions of aryl-substituted alpha-methoxystyrenes (X-1) to form
      oxocarbenium ions have been computed using the second-order Kleinert variational
      perturbation theory (KP2) in the framework of Feynman path integrals (PI) along
      with the potential energy surface obtained at the B3LYP/6-31+G(d,p) level. Good
      agreement with the experimental data was obtained, demonstrating that this novel
      computational approach for computing KIEs of organic reactions is a viable
      alternative to the traditional method employing Bigeleisen equation and harmonic
      vibrational frequencies. Although tunneling makes relatively small contributions
      to the lowering of the free energy barriers for the carboxylic acid catalyzed
      protonation reaction, it is necessary to include tunneling contributions to
      obtain quantitative estimates of the KIEs. Consideration of anharmonicity can
      further improve the calculated KIEs for the protonation of substituted alpha
      methoxystyrenes by chloroacetic acid, but for the reactions of the parent and 4
      NO(2) substituted alpha-methoxystyrene with substituted carboxylic acids, the
      correction of anharmonicity overestimates the computed KIEs for strong acid
      catalysts. In agreement with experimental findings, the largest KIEs are found in
      nearly ergoneutral reactions, DeltaG(o) approximately 0, where the transition
      structures are nearly symmetric and the reaction barriers are relatively low.
      Furthermore, the optimized transition structures are strongly dependent on the
      free energy for the formation of the carbocation intermediate, that is, the
      driving force DeltaG(o), along with a good correlation of Hammond shift in the
      transition state structure.

PMID- 19754047
TI  - 2-Substituted-4,5-dihydroxypyrimidine-6-carboxamide antiviral targeted libraries.
AB  - To identify novel potentially broad spectrum antiviral compounds against RNA
      viruses, we have developed the parallel synthesis of a structurally interesting
      class of 2-substituted-4,5-dihydroxypyrimidine-6-carboxamides. Variously 2
      substituted-4,5-dihydroxypyrimidine-6-carboxylate methyl esters were initially
      prepared and were then diversified via a facile amidation reaction. This strategy
      affords libraries of thousands of diverse drug-like compounds for screening.
      Biological evaluation of a set of these compounds, via a small initial screen,
      identified antiviral compounds against a representative RNA virus (Sendai virus,
      a paramyxovirus). We provide details on the synthetic protocols and the in vitro
      antiviral activity studies, as part of our initial investigation of the resulting
      targeted libraries.

PMID- 19754048
TI  - Determination of tetracycline residues by liquid chromatography coupled with
      electrochemical detection and solid phase extraction.
AB  - A liquid chromatography based on the reverse phase separation and a solid phase
      extraction (SPE) procedure using a phenyl-silica sorbent for the simultaneous
      separation and extraction/preconcentration of six tetracyclines was studied and
      optimized. An amperometric detector using a polycrystalline gold electrode
      operating under both DC and IPAD conditions was tested for the determination of
      the selected tetracyclines. Under optimal SPE and chromatographic conditions, the
      limit of detection of the investigated tetracyclines comprised between 50 nM (25
      microg L(-1)) and 75 nM (37 microg L(-1)), and the dynamic linear range spanned
      generally over 3 orders of magnitude, when the electrochemical detector was used
      under DC conditions at a constant applied potential of 1.6 V vs Ag/AgCl. The
      analytical method was successfully tested for the determination of tetracyclines
      in milk samples ((UHT low-fat, fresh pasteurized, and powdered milk) with
      reproducibility and recovery levels ranged between 3.1%-5.6% and 70%-118%,
      respectively.

PMID- 19754049
TI  - Heterogeneously catalyzed asymmetric hydrogenation of C=C bonds directed by
      surface-tethered chiral modifiers.
AB  - Asymmetric hydrogenation of C=C bonds is of the highest importance in organic
      synthesis, and such reactions are currently carried out with organometallic
      homogeneous catalysts. Achieving heterogeneous metal-catalyzed hydrogenation, a
      highly desirable goal, necessitates forcing the crucial enantiodifferentiating
      step to take place at the metal surface. By synthesis and application of six
      chiral sulfide ligands that anchor robustly to Pd nanoparticles and resist
      displacement, we have for the first time accomplished heterogeneous
      enantioselective catalytic hydrogenation of isophorone. High resolution XPS data
      established that ligand adsorption from solution occurred exclusively on the Pd
      nanoparticles and not on the carbon support. All ligands contained a pyrrolidine
      nitrogen to enable their interaction with the isophorone substrate while the
      sulfide functionality provided the required interaction with the Pd surface.
      Enantioselective turnover numbers of up to approximately 100 product molecules
      per ligand molecule were found with a very large variation in asymmetric
      induction between ligands: observed enantiomeric excesses increased with
      increasing size of the alkyl group in the sulfide. This likely reflects varying
      degrees of ligand dispersion on the surface: bulky substituent groups hinder
      close approach of ligand molecules to each other, inhibiting close-packed island
      formation, favoring dispersion as separate molecules, and leading to effective
      asymmetric induction. Conversely, small substituents favor island formation
      leading to very low asymmetric induction. Enantioselective reaction most likely
      involves initial formation of an enamine or iminium species, confirmed by use of
      an analogous tertiary amine, which leads to racemic product. Ligand rigidity and
      resistance to self-assembled monolayer formation are important attributes that
      should be designed into improved chiral modifiers.

PMID- 19754050
TI  - NeCl2 and ArCl2: transition from direct vibrational predissociation to
      intramolecular vibrational relaxation and electronic nonadiabatic effects.
AB  - Pump-probe results are reported for NeCl(2) excited to the Cl(2) B state,
      undergoing vibrational predissociation, and then probed via E <-- B transitions.
      Intensities, lifetimes and product vibrational branching ratios are reported for
      16 < or = v' < or = 19 Cl(2) stretching quanta. The intensity of the signal
      rapidly decreases above v' = 17. Detailed wave packet calculations of the
      vibrational predissociation dynamics are performed to determine if the
      experimental results can be explained by the onset of IVR dynamics. The
      calculations and the experiment are in close accord for low vibrational levels.
      For higher levels, some, but not all, of the loss of experimental signal can be
      attributed to IVR. To test whether electronic relaxation dynamics are important
      for NeCl(2) and ArCl(2), excited state potential surfaces that incorporate spin
      orbit coupling effects are calculated. These surfaces are then used in a wave
      packet calculation that includes both vibrational predissociation and electronic
      predissociation dynamics. The results show that electronic predissociation is
      important for ArCl(2) levels above v' = 12. For NeCl(2) the calculation suggests
      that the onset of electronic predissociation should occur for levels as low as v'
      = 13 but may not contribute markedly to the observed loss of signal above v' =
      17. Suggestions are made for further studies of this puzzling problem.

PMID- 19754051
TI  - On the local relaxation of solid neon upon Rydberg excitation of a NO impurity:
      the role of the NO(A)-Ne interaction potential and zero-point quantum
      delocalization.
AB  - The local relaxation of solid neon subsequent to the impulsive excitation of the
      NO chromophore to its A(3s sigma) Ryberg state is investigated using molecular
      dynamics simulations. This study makes use of empirical NO(X,A)-Ne isotropic pair
      potentials as well as a recently developed ab initio triatomic potential energy
      surface for the excited state. The role of these interaction potentials is
      analyzed, including many-body effects. In particular, empirical potentials,
      designed to reproduce correctly both the NO X-A steady-state absorption and
      emission bands, are shown to lead to a good description of the subpicosecond
      relaxation dynamics. The 600 fs expansion of the electronic bubble fairly agrees
      with experimental data. This relatively long time scale with respect to solid
      Argon, which was previously attributed to the range of the NO(A)-Ne interaction,
      is presumably related to the quantum nature of the medium. The time-resolved
      local relaxation of the Ne solid is understandably intermediate between that of
      classical solids (e.g., Ar) and that of quantum solids (e.g., H(2)).

PMID- 19754052
TI  - In situ and ex situ studies of platinum nanocrystals: growth and evolution in
      solution.
AB  - In situ studies on the growth and evolution of platinum nanocrystals in solution
      were carried out using synchrotron-based X-ray diffraction (XRD) techniques. Ex
      situ low- and high-resolution transmission electron microscopy (TEM) were used to
      investigate the nanocrystal morphologies through the different growth stages. In
      a reaction with low precursor concentration, both XRD and TEM results show that
      growth occurs at a relatively slow rate and yields faceted morphologies, which
      are characteristic of a thermodynamically controlled regime. In contrast, the
      platinum nanocrystals in the high-concentration reaction form branched structures
      and grow at much greater rates under a kinetically controlled regime.
      Additionally the growth mechanism of the high-concentration reaction involves a
      morphology transformation from octapod-like shapes to porous nanostructures,
      which is brought about by a novel mechanism involving selective growth and
      etching processes that occur simultaneously and at comparable rates.

PMID- 19754053
TI  - Vibrational energy transport in peptide helices after excitation of C-D modes in
      Leu-d10.
AB  - Vibrational energy transport in a short 3(10)-helical peptide is studied by time
      resolved femtosecond infrared spectroscopy. The C-D vibrations of decadeuterated
      leucine incorporated in the helical chain are excited, and the subsequent flow of
      vibrational energy through the helix is monitored by employing C horizontal lineO
      probes at various distances from the heat source as local thermometers. The C-D
      modes are not resonant to the C horizontal lineO modes, neither directly nor
      through any Fermi resonance, thereby suppressing resonant energy transfer
      directly along the C horizontal lineO oscillators of the peptide backbone. In
      contrast to our previous work (J. Phys. Chem. B 2008, 112, 9091), we no longer
      find any substantial difference in the vibrational energy transport efficiency
      after high- or low-energy excitation. That is, the heat diffusion constant of
      (2.0 +/- 0.5) A(2) ps(-1) is the same as that after depositing vibrational energy
      through the ultrafast internal conversion of a covalently bound chromophore.

PMID- 19754054
TI  - Spectroscopic analysis of tyrosine derivatives: on the role of the tyrosine
      histidine covalent linkage in cytochrome c oxidase.
AB  - 2'-(1-Imidazolyl)-4-methylphenol (C-N bonding in the ortho' position at the
      phenyl group), a model compound for a tyrosine-histidine covalent linkage, was
      studied with a combined electrochemical and UV-vis/IR spectroscopic approach.
      Electrochemical analysis of the 2'-(1-imidazolyl)-4-methylphenol model compound
      by the means of cyclic voltammetry yielded a potential of 0.48 vs ferrocene (1.15
      V vs NHE) for the oxidation of the deprotonated form, the reaction being
      kinetically irreversible. A tentative assignment of the electrochemically induced
      Fourier transform infrared (FTIR) difference infrared spectra is presented that
      indicates the deprotonation of the tyrosine before oxidation and importantly the
      strong influence of the solvent on the spectral properties and on the mechanism
      of radical formation. Fluorescence lifetimes and pre-exponential factors of the
      tyrosine-histidine model compounds are presented and discussed in comparison to
      tyrosine. The tyrosine-histidine fluorescence lifetime is found to be solvent
      dependent. The influence of the solvent on the reaction mechanism is proposed
      with regard to the mechanism of electron coupled proton transfer in proteins that
      include covalently linked amino acid side chains, like the cytochrome c oxidase.

PMID- 19754055
TI  - Science meets art--and dharma.

PMID- 19754056
TI  - Optically active (aR)- and (aS)-linear and vaulted biaryl ligands: deracemization
      versus oxidative dimerization.
AB  - The copper-mediated deracemization of the C2-symmetric vaulted biaryl ligands
      VANOL and VAPOL has been investigated. In the course of the studies that have led
      to a more reliable procedure for this process, an unprecedented oxidative
      dimerization of these ligands has been uncovered. The structures of these
      oxidative dimerization products were elucidated by a series of NMR experiments,
      and these assignments were supported by other spectroscopic techniques as well as
      their chemical reactivity. This oxidative dimerization process was not observed
      for the linear biaryl ligands BANOL and BINOL, although the new deracemization
      procedure was effective for the generation of BINOL with high optical purity. The
      (aS)-enantiomers of BINOL, VANOL and VAPOL were accessible with a copper complex
      of (-)-sparteine, and the (aR)-enantiomeric series were accessible with a copper
      complex of O'Brien's diamine. Both (-)-sparteine and O'Brien's diamine give
      higher optical purities with VANOL and VAPOL than with BINOL, and this is
      consistent with the steric congestion present in the matched and mismatched
      copper complexes of these diamines with the biaryl ligands.

PMID- 19754057
TI  - Electrophoretic mobility of silica particles in a mixture of toluene and ethanol
      at different particle concentrations.
AB  - In this paper we present measurements of the electrophoretic mobility of
      colloidal particles by using heterodyne detection of light scattering. The
      measurements have been made up to concentrations of 5.4% silica nanoparticles,
      with a diameter on the order of 80 nm, in a mixture of 70% toluene and 30%
      ethanol. To make possible the measurements at these concentrations, the liquid
      mixture is chosen so as to match the index of refraction of the particles, thus
      resulting in a transparent suspension.

PMID- 19754058
TI  - Constituent-dependent liposome structure and organization.
AB  - We have used steady state and time-resolved fluorescence spectroscopy in concert
      with TEM to study organization and dynamics of molecules comprising liposomes,
      discoidal micelles, and spherical micelles. The lipid aggregates contained
      controlled amounts of lipids with headgroups modified with a thiol-terminated
      polyethylene glycol (thio-PEG lipids) and a small amount of 1-palmitoyl-2-(pyrene
      1-yl)decanoyl-sn-glycero-3-phosphocholine (pyrene tethered DPPC), pyrene, or
      perylene as spectroscopic probes. The maximum diameter of the lipid aggregates
      was controlled by the polycarbonate filter pore size used in the extrusion
      process. The concentration of thio-PEG lipid in the aggregates determines not
      only the shape of the lipid assemblies but also the organization of the molecules
      within the assembly. Fluorescence lifetime and anisotropy decay data show that
      the immediate environment of pyrene tethered DPPC changes with the addition of
      thio-PEG lipid. In contrast, the dynamics of free chromophore (perylene) are
      insensitive to the addition of thio-PEG lipid. The addition of thio-PEG lipid to
      the lipid assembly produces changes in organization that are most pronounced in
      the lipid headgroup region. Reorientation dynamics of perylene show that the
      organization of the lipid bilayer acyl chain region is affected little by the
      addition of thio-PEG lipid and consequent macroscopic changes in the morphology
      of the lipid assemblies.

PMID- 19754059
TI  - Rb+ and Sr2+ adsorption at the TiO2 (110)-electrolyte interface observed with
      resonant anomalous X-ray reflectivity.
AB  - We report the vertical density profiles of Rb(+) and Sr(2+) at the rutile
      TiO(2)(110)-electrolyte interface for the following bulk electrolyte conditions,
      [Rb(+)] = 1 mM at pH 11 and [Sr(2+)] = 0.1 mM at pH 10.3, using X-ray
      reflectivity and resonant anomalous X-ray reflectivity. We find that Rb(+)
      specifically adsorbs with a coverage of 0.080 +/- 0.003 monolayer (ML) and a
      height of 3.72 +/- 0.03 A above the surface Ti-O plane. In comparison, Sr(2+)
      adsorbs with a coverage of 0.40 +/- 0.07 ML and an average height of 3.05 +/-
      0.16 A, but with a significant vertical distribution width (0.35 +/- 0.02 A). The
      Sr(2+) distribution in the presence of a background electrolyte ([Na(+)] = 30 mM)
      was also investigated, and it is found that, while the ion height and coverage
      are unchanged within the uncertainties of the measurements, the width of the
      distribution is apparently increased in the presence of Na(+). Comparison is made
      with previous results, including XR and X-ray standing waves (XSW) measurements,
      and molecular dynamics simulations. Our results are in excellent agreement with a
      recently proposed multisite adsorption mechanism that suggests simultaneous
      adsorption in two inner-sphere adsorption geometries, the tetradentate and the
      bidentate sites.

PMID- 19754060
TI  - Microporous coordination polymers as selective sorbents for liquid
      chromatography.
AB  - We evaluate the potential of microporous coordination polymers (MCPs) to act as
      the stationary phase in liquid chromatographic separations. MCPs derived from
      carboxylates coordinated to copper (HKUST-1) and zinc (MOF-5) were studied. The
      shape and size selective separation of organic compounds including benzene,
      ethylbenzene, styrene, naphthalene, anthracene, phenanthrene, pyrene, 1,3,5
      triphenylbenzene, and 1,3,5-tris(4-bromophenyl)benzene was performed, and in most
      cases excellent separation was achieved based on a combination of molecular
      sieving and adsorption effects.

PMID- 19754061
TI  - TiO2 thin films self-assembled with a partly fluorinated surfactant template.
AB  - New TiO(2) films have been self-assembled on solid substrate by dip-coating using
      TiCl(4) as the titanium source and the partly fluorinated surfactant
      F(CF(2))(8)C(2)H(4)(OC(2)H(4))(9)OH as the liquid crystal template. By control
      over the dip-withdrawal speed, film thicknesses from a minimum of 43 nm were
      produced with rms roughnesses of 0.5-0.7 nm. The films were characterized by X
      ray reflectivity, grazing incidence small-angle X-ray scattering, atomic force
      microscopy, contact angle measurements, and Raman spectroscopy. Their GI-SAXS
      patterns are characteristic of a 2-D hexagonal structure in which tubular rods of
      the fluorinated surfactant are packed hexagonally and aligned parallel to the
      substrate. Reflectivity and contact angle measurements of the as-prepared film
      indicate that a low-density hydrophilic TiO(2) surface presents to the air.

PMID- 19754062
TI  - Nonequilibrium phase transformations at the air-liquid interface.
AB  - A theoretical model is presented for the formation of an ordered phase close to
      the air-liquid interface of an open binary aqueous solution. The chemical
      potential of water in the liquid phase is, in general, not equal to the chemical
      potential of water in the ambient atmosphere. There are therefore nonequilibrium
      conditions close to the air-liquid interface. There is also a gradient in the
      chemical potential of water, which could lead to the formation of a new
      interfacial phase. The formation of an interfacial phase is analyzed in terms of
      the equilibrium phase behavior corresponding to the local water chemical
      potential. The possibility of forming an interfacial phase is strongly dependent
      on the ambient conditions, bulk composition, and diffusive transport properties
      of the phases in question. Explicit calculations are presented for the formation
      of a lamellar liquid-crystalline phase close to the air-liquid interface of an
      isotropic surfactant solution with parameters chosen from the sodium bis(2
      ethylhexyl)sulfosuccinate (AOT)/water system. We consider the relevance of the
      model to neutron reflectivity studies of the interface between air and
      surfactant/water systems, as well as to surfactant/polymer/water systems.

PMID- 19754063
TI  - Dual-emissive photoluminescent Langmuir-Blodgett films of decatungstoeuropate and
      an amphiphilic iridium complex.
AB  - Langmuir monolayers and Langmuir-Blodgett (LB) films of the decatungstoeuropate
      [Eu(W(5)O(18))(2)](9-) (EuW(10)) and the amphiphilic Ir complex 1 have been
      successfully fabricated by using the adsorption properties of the EuW(10)
      polyanion dissolved in the aqueous subphase onto a positively charged 1 monolayer
      at the air-water interface. The compression isotherms and Brewster angle
      microscopy (BAM) of monolayers of 1 on pure water (1 monolayer) and on a subphase
      containing 10(-6) M EuW(10) and 10(-3) M NaCl (1/EuW(10) monolayer) have been
      studied. Infrared and UV-vis spectroscopy of the transferred LB films indicate
      that EuW(10) and 1 molecules are incorporated within these LB films. X-ray
      reflectivity (SXR) and atomic force microscopy (AFM) experiments indicate that LB
      films of 1 present a heterogeneous morphology while 1/EuW(10) films show a
      flatter and more homogeneous surface as well as a layered structure with a
      periodicity of 4.1 nm. Mixed monolayers of 1 and DODA
      (dimethyldioctadecylammonium bromide) have been prepared with EuW(10) polyanions
      in the subphase to control the concentration of 1 and EuW(10) polyanions within
      the LB films. AFM and SXR experiments with the transferred LB films show that the
      dilution of 1 with DODA improves the layered structure. The luminescence of 1 is
      partially quenched by EuW(10) in the 1/EuW(10) LB films, while emission from
      EuW(10) is not detected. On the other hand, emission from both entities is
      preserved in the LB films prepared from mixed DODA/1 monolayers, in which the red
      and yellow emissions arise independently from EuW(10) and 1, respectively. The
      different DODA:1 ratios lead to changes in the emission color. Therefore, they
      constitute a promising color-tunable luminescent material.

PMID- 19754064
TI  - Amphoteric core-shell microgels: contraphilic two-compartment colloidal
      particles.
AB  - pH-responsive amphoteric core-shell microgel particles were synthesized by
      emulsion copolymerization of the appropriate functional monomers with ethylene
      glycol dimethacrylate as the cross-linker. 2-(Diethylamino)ethyl methacrylate
      (DEA) was used as the ionizable basic monomer, and tert-butyl methacrylate served
      as the hydrophobic monomer precursor, which gave the methacrylic acid (MAA)
      moieties following acid hydrolysis of the ester groups. The core of the
      polyampholyte microgels comprised a cross-linked poly(2-(diethylamino)ethyl
      methacrylate) (PDEA) or poly(methacrylic acid) (PMAA) network surrounded by a
      cross-linked PMAA or PDEA shell, respectively. A polyampholyte random copolymer
      microgel with the DEA and MAA units randomly distributed within the gel phase was
      also prepared. Scanning electron microscopy studies showed spherical particles of
      a narrow size distribution, and transmission electron microscopy verified the
      core-shell topology of the particles. Potentiometric titration curves revealed
      two plateau regions for the polyampholyte core-shell microgels attributed to the
      independent ionization process of the core and the shell of the particles, in
      contrast to the random copolymer microgel particles that exhibited a single
      plateau region as a result of the simultaneous protonation/deprotonation process
      of the basic and acidic moieties of the microgels. The core and the shell of the
      particles were found to swell independently upon ionization of the DEA or MAA
      moieties at low or high pH, respectively, whereas collapsed latex particles were
      obtained in the intermediate pH range when both the core and the shell of the
      particles were neutral, in agreement with the potentiometric titration data.
      These core-shell microgels comprise novel two-compartment nanostructures that
      exhibit contraphilic properties in the core and the shell of the particles in
      response to a single external stimulus.

PMID- 19754065
TI  - Shadow overlap ion-beam lithography for nanoarchitectures.
AB  - Precisely constructed nanoscale devices and nanoarchitectures with high spatial
      resolution are critically needed for applications in high-speed electronics, high
      density memory, efficient solar cells, optoelectronics, plasmonics, optical
      antennas, chemical sensors, biological sensors, and nanospectroscopic imaging.
      Current methods of classical optical lithography are limited by the diffraction
      effect of light for nanolithography, and the state of art of e-beam or focused
      ion beam lithography limit the throughput and further reduction less than few
      nanometers for large-area batch fabrication. However, these limits can be
      surpassed surprisingly by utilizing the overlap of two shadow images. Here we
      present shadow overlap of ion-beam lithography (SOIL), which can combine the
      advantages of parallel processing, tunable capability of geometries, cost
      effective method, and high spatial resolution nanofabrication technique. The SOIL
      method relies on the overlap of shadows created by the directional metal
      deposition and etching angles on prepatterned structures. Consequently, highly
      tunable patterns can be obtained. As examples, unprecedented nanoarchitectures
      for optical antennas are demonstrated by SOIL. We expect that SOIL can have a
      significant impact not only on nanoscale devices, but also large-scale (i.e.,
      micro and macro) three-dimensional innovative lithography.

PMID- 19754066
TI  - Graphitic electrical contacts to metallic single-walled carbon nanotubes using Pt
      electrodes.
AB  - We investigate electronic devices consisting of individual, metallic, single
      walled carbon nanotubes contacted by Pt electrodes in a field effect transistor
      configuration, focusing on improvements to the metal-nanotube contact resistance
      as the devices are annealed in inert environments including ultrahigh vacuum. At
      moderate temperatures (T < 880 K), thermal processing results in high resistance
      contacts with thermally activated barriers. Higher temperatures (T > 880 K)
      achieve nearly transparent contacts. In the latter case, analytical surface
      measurements reveal the catalytic decomposition of hydrocarbons into graphene
      layers on the Pt surface, suggesting that improved electronic behavior is
      primarily due to the formation of an all-carbon nanotube-graphite interface
      rather than to the improvement of the nanotube-Pt one.

PMID- 19754067
TI  - Plasmonic nanogalaxies: multiscale aperiodic arrays for surface-enhanced Raman
      sensing.
AB  - The accurate and reproducible control of intense electromagnetic fields localized
      on the nanoscale is essential for the engineering of optical sensors based on the
      surface-enhanced Raman scattering (SERS) effect. In this paper, using rigorous
      generalized Mie theory (GMT) calculations and a combined top-down/bottom-up
      nanofabrication approach, we design and experimentally demonstrate approximately
      10(8) spatially averaged, reproducible SERS enhancement in deterministic
      aperiodic arrays of Au nanoparticles with different length scales. Deterministic
      aperiodic arrays of 200 nm diameter nanocylinders are first fabricated using
      electron-beam lithography on quartz substrates, and smaller size (30 nm diameter)
      Au nanoparticles are subsequently positioned by in situ Au reduction at regions
      of maximum field enhancement. These multiscale structures, which we call
      "plasmonic nanogalaxies", feature a cascade enhancement effect due to the strong
      electromagnetic interactions of small satellite nanoparticles with localized
      fields in aperiodic arrays of nanocylinders. The development of SERS substrates
      based on aperiodic arrays with different length scales provides a novel strategy
      to engineer plasmon-enhanced biosensors with chemical fingerprinting capability.

PMID- 19754068
TI  - Strong polarization dependence of plasmon-enhanced fluorescence on single gold
      nanorods.
AB  - We report on the strong polarization dependence of the plasmon-enhanced
      fluorescence on single gold nanorods. The fluorescence from the organic
      fluorophores that are embedded in a mesostructured silica shell around individual
      gold nanorods is enhanced by the longitudinal plasmon resonance of the nanorods.
      Our electrostatic calculations show that under an off-resonance excitation, the
      electric field intensity contour around a nanorod rotates away from the length
      axis as the excitation polarization is varied. The polarization dependence of the
      plasmon-enhanced fluorescence is ascribed to the dependence of the averaged
      electric field intensity enhancement within the silica shell on the excitation
      polarization. The measured fluorescence enhancement factor is in very good
      agreement with that obtained from the electrostatic calculations. The
      fluorescence enhancement factor increases as the longitudinal plasmon wavelength
      is synthetically tuned close to the excitation wavelength. In addition, the
      polarization dependence is used to determine the orientation angle of the gold
      nanorods. The results are in excellent agreement with the actual measurements.
      Furthermore, the emission spectrum of the fluorophore is modified by the
      longitudinal plasmon resonance of the gold nanorods. A linear correlation between
      the emission peak wavelength and the longitudinal plasmon wavelength is obtained.

PMID- 19754069
TI  - Controlling the locus of bubble nucleation by dissolved gases in heterogeneous
      liquid-liquid systems.
AB  - We have examined the nucleation of chemically generated nitrogen gas bubbles in
      microheterogeneous systems, using optical microscopy on a model system consisting
      of a single liquid-liquid interface. Results clearly show that bubble nucleation
      occurs in both the aqueous and oil phases, despite the nitrogen production
      reaction being a purely aqueous phase process. A theoretical model is developed
      which describes the time evolution of the nitrogen concentration profile, and
      this reveals that bubbles in the oil are a result of homogeneous nucleation of
      dissolved N(2) transported across the interface into a (supersaturated) diffusion
      layer. We further show that bubble nucleation in the oil can be inhibited or
      eliminated by adding water-soluble surfactants, which facilitates aqueous phase
      bubble nucleation and then acts as highly effective nitrogen sinks, severely
      reducing the flux of dissolved gas across the water-oil interface.

PMID- 19754070
TI  - Triggered instability of liposomes bound to hydrophobically modified core-shell
      PNIPAM hydrogel beads.
AB  - The ability to trigger a destabilization of the membrane integrity of liposomes
      bound to environmentally sensitive hydrophobically modified core-shell hydrogel
      beads is demonstrated. Hydrogel beads with a core composed of poly(N
      isopropylacrylamide) lightly cross-linked with bisacrylamide (BA) (pNIPAM) and a
      shell composed of NIPAM highly cross-linked with BA and containing varying
      amounts of acrylic acid (AA) [p(NIPAM-co-AA)] undergo a volume phase transition
      (VPT) at approximately 32 degrees C, as determined from (1)H magic angle spinning
      (MAS) NMR, regardless of the AA content of the shell. When the shell was
      hydrophobically modified with either decylamine or tetradecylamine, binding of
      extruded large unilamellar vesicles (eLUVs) composed of 1-palmitoyl-2
      oleoylphosphatidylcholine (POPC) was quantitative, as determined via fluorescence
      spectroscopy. Fluorescence microscopy showed that such bound eLUVs did not fuse.
      Hydrogel-bound eLUV membrane permeability was assessed using (31)P MAS NMR in the
      presence of the chemical shift agent praseodymium and demonstrated that only at
      lower degrees of hydrophobic modification of the core-shell hydrogels was eLUV
      membrane barrier integrity maintained when T < VPT. At a low degree of
      hydrophobic modification, cycling the temperature above the VPT even for short
      periods caused the eLUV membranes to become leaky. Hence, eLUV membrane
      permeability was coupled to the hydrogel VPT, a situation that would be useful in
      applications requiring triggered release of liposomal contents.

PMID- 19754071
TI  - Tuning of an optical dimer nanoantenna by electrically controlling its load
      impedance.
AB  - Optical antennas are elementary units used to direct optical radiation to the
      nanoscale. Here we demonstrate an active control over individual antenna
      performances by an external electrical trigger. We find that by an in-plane
      command of an anisotropic load medium, the electromagnetic interaction between
      individual elements constituting an optical antenna can be controlled, resulting
      in a strong polarization and tuning response. An active command of the antenna is
      a prerequisite for directing light wave through the utilization of such a device.

PMID- 19754072
TI  - Asymmetric Michael addition of gamma,gamma-disubstituted alpha,beta-unsaturated
      aldehydes to nitroolefins via dienamine catalysis.
AB  - The first chemo- and alpha-regioselective asymmetric Michael addition of
      gamma,gamma-disubstituted alpha,beta-unsaturated aldehydes to nitroolefins has
      been presented in excellent diastereo- and enantioselectivities (dr up to >99:1,
      93-96% ee) via dienamine catalysis. The Michael adducts have been efficiently
      converted to a number of optically pure cyclic frameworks with versatile scaffold
      diversity.

PMID- 19754073
TI  - Highly efficient and versatile synthesis of polyarylfluorenes via Pd-catalyzed C
      H bond activation.
AB  - A facile protocol for the Pd-catalyzed preparative synthesis of fluorene
      derivatives has been developed. While a wide range of fluorenes were easily
      obtained with high efficiency and selectivity under mild conditions, excellent
      functional group tolerance was also demonstrated. On the basis of Hammett and KIE
      studies, the present reaction is proposed to proceed via a base-assisted
      deprotonative metalation pathway.

PMID- 19754074
TI  - Mechanistic comparison between Pd-catalyzed ligand-directed C-H chlorination and
      C-H acetoxylation.
AB  - This communication describes detailed investigations of the mechanism of the Pd
      catalyzed C-H chlorination and acetoxylation of 2-o-tolylpyridine. Under the
      conditions examined, both reactions proceed via rate-limiting cyclopalladation.
      However, substrate and catalyst order as well as Hammett data indicate that the
      intimate mechanism of cyclopalladation differs significantly between PdCl2
      catalyzed chlorination and Pd(OAc)2-catalyzed acetoxylation.

PMID- 19754075
TI  - Penetration and adsorption of a water droplet causing local deformation of the
      poly(methyl methacrylate) surface.
AB  - A molecular dynamics approach has been employed to study the wetting behavior of
      poly(methyl methacrylate) (PMMA). The flexible and rigid models of PMMA substrate
      are compared. The results verify that the rigid model is not suitable to act as
      the PMMA substrate in simulation because it prevents the diffusion of PMMA
      molecules, which affects the penetration behavior of water molecules. The contact
      angle of different sizes of water droplets on the PMMA surface and local root
      mean-square roughness have been calculated. The local root-mean-square roughness
      increases with decreasing size of water droplet. As the number of water molecules
      in the droplet falls below 1000, the contact angle of the water droplet and the
      permeability of the PMMA substrate are affected significantly because of the
      lower adsorption energy between the water molecules and the diffusion of the
      outmost PMMA molecules on the surface. When the droplet is composed of more than
      1000 water molecules, the contact angle shows an agreement with experimental
      results. Finally, the hydrogen-bonded number as a function of distance along the
      Z direction and the distribution of the hydrogen-bonded number and adjacent
      number in different regions are discussed, with results showing that the hydrogen
      bonded number is in inverse proportion to the number of water molecules of the
      droplet in the region below the dividing surface.

PMID- 19754076
TI  - Comment on "Ultrafast dynamics of polarons in conductive polyaniline: comparison
      of primary and secondary doped forms".

PMID- 19754077
TI  - Structure and dynamics of cold-adapted enzymes as investigated by phosphorescence
      spectroscopy and molecular dynamics studies. 2. The case of an esterase from
      Pseudoalteromonas haloplanktis.
AB  - Enzymes from psychrophiles display high catalytic efficiency at low temperatures.
      As a consequence, there is a lot of academic and industrial interest in
      investigating the molecular strategies adopted from these enzymes to work in
      conditions where other enzymes are almost inactive. Recently, a novel esterase
      activity was identified and isolated from the cold-adapted organism
      Pseudoalteromonas haloplanktis. The enzyme, named PhEST, is a dimer with a
      molecular mass of 60 kDa composed of two identical subunits. PhEST possesses four
      tryptophan residues that are homogenously dispersed in the protein tertiary
      organization. In this work, we used phosphorescence spectroscopy and molecular
      dynamics experiments to investigate the structural properties of PhEST. The
      obtained model structure of PhEST indicates that the environments of tryptophan
      residues W14 and W50 are characterized by limited conformational freedom. On the
      contrary, the environments of the tryptophan residues W181 and W197 are
      relatively mobile owing to enhanced fluctuations of residues 93-99 and 192-195,
      respectively, flexible loops that join segments of the protein secondary
      structure. The high-resolution phosphorescence spectrum in low-temperature
      glasses distinguishes two classes of Trp environments in PhEST structure: one
      class that is typical of compact internal hydrophobic sites, and the other class
      that is characteristic of disordered and/or partly solvent exposed regions. The
      phosphorescence lifetime of PhEST registered in fluid solution is invariably
      short, indicating that some Trp residues are in rather flexible superficial sites
      of the globular fold, whereas internal chromophores are strongly quenched by the
      proximity to Cys residues. Acrylamide and O(2) quenching studies pointed out that
      the internal protein site is compact and rigid, typical of beta-barrel core
      structures. Every spectroscopic feature described in this work is well accounted
      for by the proposed model structure of PhEST.

PMID- 19754078
TI  - Molecular dynamics simulation study of correlated motions in phospholipid bilayer
      membranes.
AB  - A 100 ns simulation of a fluid phase dioleoylphosphatidylcholine bilayer,
      consisting of 288 lipid molecules at full hydration, has been studied to describe
      in detail the lateral translational motion of individual lipid molecules.
      Analysis of the simulation trajectories suggests that correlated motion between
      neighboring lipid molecules is an important aspect of lipid dynamics. The
      correlation among neighboring lipids within a monolayer is substantial and
      surprisingly long-ranged with a decay length of approximately 25 A. This provides
      a mechanism for the previously published observation that lateral diffusion
      coefficients computed from molecular dynamics simulations exhibited a strong
      dependence on the size of the unit cell and for the recent suggestion that lipid
      flows on that nanoscale are an important component of translational diffusion
      within membranes. Additionally, we show that diffusive motion is only weakly
      correlated between lipids in opposing monolayers.

PMID- 19754079
TI  - Measurement of the second-order hyperpolarizability of the collagen triple helix
      and determination of its physical origin.
AB  - We performed Hyper-Rayleigh Scattering (HRS) experiments to measure the second
      order nonlinear optical response of the collagen triple helix and determine the
      physical origin of second harmonic signals observed in collagenous tissues. HRS
      experiments yielded a second-order hyperpolarizability of 1.25 x 10(-27) esu for
      rat-tail type I collagen, a surprisingly large value considering that collagen
      presents no strong harmonophore in its amino acid sequence. Polarization-resolved
      experiments showed intramolecular coherent contributions to the HRS signal along
      with incoherent contributions that are the only contributions for molecules with
      dimensions much smaller than the excitation wavelength. We therefore modeled the
      effective second-order hyperpolarizability of the 290 nm long collagen triple
      helix by summing coherently the nonlinear response of well-aligned moieties along
      the triple helix axis. This model was confirmed by HRS measurements after
      denaturation of the collagen triple helix and for a collagen-like short model
      peptide [(Pro-Pro-Gly)(10)](3). We concluded that the large collagen nonlinear
      response originates in the tight alignment of a large number of small and weakly
      efficient harmonophores, presumably the peptide bonds, resulting in a coherent
      amplification of the nonlinear signal.

PMID- 19754080
TI  - Dynamical transition in a small helical peptide and its implication for
      vibrational energy transport.
AB  - The two-dimensional infrared spectrum of an octameric helical peptide in
      chloroform was measured as a function of temperature. Isotope labeling of the
      carbonyl group of one of the amino acids was used to obtain information for an
      isolated vibration. The antidiagonal width of the 2D-IR signal, which is a
      measure of the homogeneous dephasing time T(2), is constant from 220 to 260 K
      (within experimental error), and increases steeply above. The homogeneous
      dephasing time of the carbonyl vibration is attributed to the flexibility of the
      system and/or its immediate surrounding. The system undergoes a dynamical
      transition at about 270 K, with similarities to the protein dynamical transition.
      Furthermore, the temperature dependence of the antidiagonal width strongly
      resembles that of the efficiency of vibrational energy transport along the helix,
      which has been studied in a recent paper (J. Phys. Chem. B 2008, 112, 15487). The
      connection between the two processes, structural flexibility and energy transport
      mechanism, is discussed.

PMID- 19754081
TI  - Aggregation of water-soluble conjugated polymers in Couette shear flow.
AB  - Aqueous solutions of the conjugated polymer poly(2,5-disulfopropoxy-1,4-phenylene
      vinylene) (DPS-PPV) blended with poly(vinyl alcohol) (PVA) have been exposed to
      Couette shear flow and studied using fluorescence techniques. Significant
      aggregation of the DPS-PPV and PVA molecules occurred during shear exposure,
      resulting in an 80% decrease in solution fluorescence intensity and formation of
      visible polymer particles. The aggregation process caused a separation of the DPS
      PPV molecules where the fluorescence of the aggregated particles had a red
      shifted emission peak at a wavelength of 594 nm, and the remaining solution had a
      blue-shifted emission at 513 nm, as compared to an initial emission peak at 574
      nm. The fluorescence excitation spectra of the aggregated particles became
      broadened while the excitation peak of the remaining solution narrowed. This has
      great implications for the processing of aqueous conjugated polymer systems in
      various polymer blends, because aggregation could cause significant problems for
      device manufacture.

PMID- 19754082
TI  - Temperature-dependent exciton dynamics in J-aggregates-when disorder plays a
      role.
AB  - Absorption and fluorescence spectral properties of J-aggregates of core
      tetrasubstituted perylene bisimide (PBI) dyes have been investigated in the
      temperature range from 300 to 5 K. A special feature of the present PBI J
      aggregates is that, in contrast to classical J-aggregates like that of
      pseudoisocyanine (PIC), the chromophores are held together not only by van-der
      Waals interactions but also by hydrogen bonds. The temperature dependence of the
      spectral band widths and the Stokes shift for PBI 1 aggregates are compared with
      those for 3,3'-bis-(3-sulfopropyl)-5,5'-dichloro-9-ethylthiacarbocyanine (THIATS)
      J-aggregates, which have been studied in detail previously (J. Phys. Chem. B
      2001, 105, 4636-4646). The assemblies of PBI 1 possess very broad absorption
      bands compared to those of THIATS, even at low temperature (5 times broader). We
      interpret this observation as an indication for a very large level of disorder in
      the case of PBI 1 assemblies. Possible sources of disorder in aggregates of PBI 1
      are discussed. Despite large quantitative differences, both aggregates show
      qualitatively the same temperature dependence of the Stokes shift calculated in
      units of fluorescence bandwidth. The observed temperature dependences are
      discussed in terms of exciton thermal population of different states of
      disordered aggregates. Unexpectedly low thermal activation energy of exciton
      migration is observed for PBI 1 aggregates.

PMID- 19754083
TI  - A coarse-grained model for polyethylene oxide and polyethylene glycol:
      conformation and hydrodynamics.
AB  - A coarse-grained (CG) model for polyethylene oxide (PEO) and polyethylene glycol
      (PEG) developed within the framework of the MARTINI CG force field (FF) using the
      distributions of bonds, angles, and dihedrals from the CHARMM all-atom FF is
      presented. Densities of neat low molecular weight PEO agree with experiment, and
      the radius of gyration R(g) = 19.1 A +/- 0.7 for 76-mers of PEO (M(w)
      approximately 3400), in excellent agreement with neutron scattering results for
      an equal sized PEG. Simulations of 9, 18, 27, 36, 44, 67, 76, 90, 112, 135, and
      158-mers of the CG PEO (442 < M(w) < 6998) at low concentration in water show the
      experimentally observed transition from ideal chain to real chain behavior at
      1600 < M(w) < 2000, in excellent agreement with the dependence of experimentally
      observed hydrodynamic radii of PEG. Hydrodynamic radii of PEO calculated from
      diffusion coefficients of the higher M(w) PEO also agree well with experiment.
      R(g) calculated from both all-atom and CG simulations of PEO76 at 21 and 148
      mg/cm(3) are found to be nearly equal. This lack of concentration dependence
      implies that apparent R(g) from scattering experiments at high concentration
      should not be taken to be the chain dimension. Simulations of PEO grafted to a
      nonadsorbing surface yield a mushroom to brush transition that is well described
      by the Alexander-de Gennes formalism.

PMID- 19754084
TI  - Sugar radical formation by a proton coupled hole transfer in 2'-deoxyguanosine
      radical cation (2'-dG*+): a theoretical treatment.
AB  - Previous experimental and theoretical work has established that electronic
      excitation of a guanine cation radical in nucleosides or in DNA itself leads to
      sugar radical formation by deprotonation from the dexoxyribose sugar. In this
      work, we investigate a ground electronic state pathway for such sugar radical
      formation in a hydrated one electron oxidized 2'-deoxyguanosine (dG(*+) +
      7H(2)O), using density functional theory (DFT) with the B3LYP functional and the
      6-31G* basis set. We follow the stretching of the C(5')-H bond in dG(*+) to gain
      an understanding of the energy requirements to transfer the hole from the base to
      sugar ring and then to deprotonate to proton acceptor sites in solution and on
      the guanine ring. The geometries of reactant (dG(*+) + 7H(2)O), transition state
      (TS) for deprotonation of the C(5') site, and product (dG((*)C(5'), N(7)-H(+)) +
      7H(2)O) were fully optimized. The zero point energy (ZPE) corrected activation
      energy (TS) for the proton transfer (PT) from C(5') is calculated to be 9.0
      kcal/mol and is achieved by stretching the C(5')-H bond by 0.13 A from its
      equilibrium bond distance (1.099 A). Remarkably, this small bond stretch is
      sufficient to transfer the "hole" (positive charge and spin) from guanine to the
      C(5') site on the deoxyribose group. Beyond the TS, the proton (H(+))
      spontaneously adds to water to form a hydronium ion (H(3)O(+)) as an
      intermediate. The proton subsequently transfers to the N(7) site of the guanine
      (product). The 9 kcal/mol barrier suggests slow thermal conversion of the cation
      radical to the sugar radical but also suggests that localized vibrational
      excitations would be sufficient to induce rapid sugar radical formation in DNA
      base cation radicals.

PMID- 19754085
TI  - Kinetic study of the aroxyl radical-scavenging reaction of alpha-tocopherol in
      methanol solution: notable effect of the alkali and alkaline earth metal salts on
      the reaction rates.
AB  - A kinetic study of the aroxyl (ArO*) radical-scavenging reaction of alpha
      tocopherol (alpha-TocH) has been performed in the presence of six kinds of alkali
      and alkaline earth metal salts (LiI, LiClO(4), NaI, NaClO(4), KI, and
      Mg(ClO(4))(2)) in methanol solution, using stopped-flow spectrophotometry. The
      decay rate of the ArO* for the reaction of alpha-TocH with ArO* increased
      linearly with increasing concentration of metal salts. The second-order rate
      constants (k(s)) for the reaction of alpha-TocH with ArO* increased in the order
      of no metal salt < KI approximately NaClO(4) approximately NaI <or= LiClO(4) <
      Mg(ClO(4))(2) < LiI at the same concentration of metal salts. For example, the
      k(s) values in methanol solution including 4.00 x 10(-1) M of LiI and
      Mg(ClO(4))(2) were 3.04 and 1.30 times larger than that in the absence of metal
      salts, respectively. The alkali and alkaline earth metal salts having smaller
      ionic radius of cation and anion and larger charge of cation gave larger rate
      constants (k(s)). Effects of metal cations on the UV-vis absorption spectra of
      the alpha-Toc* (and ArO*) radical were negligible in methanol solution,
      suggesting that the complex formation between the alpha-Toc* (and ArO*) radical
      molecule and metal cations is hindered by the hydrogen bond between radical and
      methanol molecules. The results indicate that the hydrogen transfer reaction of
      alpha-TocH proceeds via an electron transfer intermediate from alpha-TocH to ArO*
      radicals followed by proton transfer. Both the coordinations of metal cations to
      the one-electron reduced anions of ArO* (ArO: (-)) and of counteranions to the
      one-electron oxidized cations of alpha-TocH (alpha-TocH(+)*) may stabilize the
      intermediate, resulting in the acceleration of electron transfer. On the other
      hand, the effect of metal salts on the rate of bimolecular self-reaction (2k(d))
      of the alpha-Toc* radical was not observed. The result suggests that the hydrogen
      transfer reaction between two alpha-Toc* radical molecules proceeds via a one
      step hydrogen atom transfer mechanism rather than via an electron-transfer
      intermediate. High concentrations of alkali and alkaline earth metal salts
      coexist with alpha-TocH in plasma, blood, and many tissues, suggesting the
      contribution of the metal salts to the antioxidant actions of alpha-TocH.

PMID- 19754087
TI  - Enzymatic catalysis: the emerging role of conceptual density functional theory.
AB  - Experimentalists and quantum chemists are living in a different world. A wealth
      of theoretical enzymology-related publications is hardly known by
      experimentalists, and vice versa. Our aim is to bring both worlds together and to
      show the powerful possibilities of a multidisciplinary approach to study subtle
      details of complicated enzymatic processes to a broad readership. MD simulations
      and QM/MM approaches often focus on the calculation of reaction paths based on
      activation energies, which is a time-consuming task. A valuable alternative is
      the reactivity descriptors founded in conceptual DFT like softness,
      electrophilicity, and the Fukui function, which describe the kinetic aspects of a
      reaction in terms of the response to perturbations in N and/or upsilon(r),
      typical for a chemical reaction, of the reagents in the ground state. As such,
      the relative energies at the beginning of the reaction predict a sequence of
      activation energies only based on the properties of the reactants (Figure 5 ). In
      2003, Geerlings et al. published a key review giving a detailed description of
      the principles and concepts of conceptual DFT and highlighting its success to
      study generalized acid/base reactions including addition, substitution, and
      elimination reactions. Since the time that this review appeared, conceptual DFT
      has proven its strength in literally hundreds of papers with application to
      organic and inorganic reactions. Its role in unravelling enzymatic reaction
      mechanisms, in handling experimentally difficult accessible biochemical problems,
      and in the interpretation of biochemical experimental observations is emerging
      and very promising.

PMID- 19754088
TI  - Impact of globule unfolding on dilational viscoelasticity of beta-lactoglobulin
      adsorption layers.
AB  - The dynamic surface dilational elasticity, surface pressure, and adsorbed amount
      of the mixed solutions of beta-lactoglobulin and guanidine hydrochloride were
      measured as a function of surface age and denaturant concentration. It was shown
      that the conformational transition from compact globules to disordered protein
      molecules in the surface layer leads to strong changes in the surface elasticity
      kinetic dependencies and thereby can be easily detected by measuring the surface
      dilational rheological properties. The corresponding changes of the kinetic
      dependencies of the surface pressure and adsorbed amount are not so pronounced
      but correlate with the results on surface dilational elasticity.

PMID- 19754086
TI  - Prediction of the water content in protein binding sites.
AB  - An efficient molecular simulation methodology has been developed to determine the
      positioning of water molecules in the binding site of a protein or protein-ligand
      complex. Occupancies and absolute binding free energies of water molecules are
      computed using a statistical thermodynamics approach. The methodology, referred
      to as Just Add Water Molecules (JAWS), features "theta-water" molecules that can
      appear and disappear on a binding-site grid. Key approximations render the
      technique far more efficient than conventional free energy simulations. Testing
      of JAWS on five diverse examples (neuraminidase, scytalone dehydratase, major
      urinary protein 1, beta-lactoglobulin, and COX-2) demonstrates its accuracy in
      locating hydration sites in comparison to results from high-resolution crystal
      structures. Possible applications include aid in refinement of protein crystal
      structures, drug lead optimization, setup of docking calculations, and
      simulations of protein-ligand complexes.

PMID- 19754089
TI  - Multi-functional thermosensitive composite microspheres with high magnetic
      susceptibility based on magnetite colloidal nanoparticle clusters.
AB  - Monodisperse organic/inorganic composite microspheres with well-defined structure
      were prepared through the encapsulation of silica coated superparamagnetic
      magnetite colloidal nanoparticle clusters (CNCs) with cross-linked poly(N
      isopropylacrylamide) (PNIPAM) shell. At first, the sub-micrometer-sized CNCs were
      fabricated by the solvothermal process, and then a silica layer was coated on the
      surface of CNCs through a sol-gel process, and finally, a thermoresponsive shell
      of PNIPAM was deposited onto the surface of the core/shell magnetic microspheres
      by a precipitation polymerization. The experimental results showed that the size
      of Fe(3)O(4) core, the thickness of SiO(2) shell, as well as volume phase
      transition temperature (VPTT) of PNIPAM shell could be well controlled, and this
      structured modulation could satisfy different requirements. The superparamagnetic
      behavior, high magnetization (the saturation magnetization of
      Fe(3)O(4)/SiO(2)/PNIPAM microspheres with a 10% cross-linking density is 41.6
      emu/g), and good thermosensitivity make these composite microspheres an ideal
      candidate for various important applications such as in controlled drug delivery,
      bioseparation, and catalysis.

PMID- 19754090
TI  - Catalytic coupling of CO2 with epoxide over supported and unsupported amines.
AB  - Catalytic coupling of carbon dioxide with epoxide to cyclic carbonate is an
      important reaction that has recently been receiving renewed interest. This route
      allows the use of carbon dioxide as a greener chemical feedstock, which
      challenges the current practices for the synthesis of cyclic carbonates and
      derivatives. The present study is mainly concerned with catalytic coupling
      reaction between CO(2) and propylene oxide using organic amine as catalyst. The
      structural aspects of amines and the effects of their immobilization on solid
      surfaces on reaction kinetics are particularly studied. It is found that 1,5,7
      triazabicyclo[4,4,0]dec-5-ene (TBD) amine maintains high catalytic activity both
      with and without solid support, but other primary amines, such as p
      phenylenediamine give much reduced activity when placed on a solid surface. It is
      attributed to the absence of surface hydrogen in the supported TBD, prohibiting
      the catalyst sites from CO(2) poisoning. The coupling of other epoxides,
      including epichlorohydrin and styrene oxide over the solid supported amine, is
      also briefly carried out. Reaction mechanisms are proposed to explain the
      experimental observations.

PMID- 19754091
TI  - Photodissociation imaging of diatomic sulfur (S2).
AB  - The photodissociation of diatomic sulfur, S(2), in the region of the first
      dissociation limit is studied with velocity map imaging. Correlated fine
      structure distributions P(J1,J2) for the two S((3)P(J)) fragments are determined
      at selected photolysis wavelengths. Image analysis of the speed distributions of
      the atomic fragments following product-state-specific detection results in a
      revision of the bond energy to D(0) = 35636.9 +/- 2.5 cm(-1) with respect to the
      lowest rovibrational level. This value arises from reinterpretation of previous
      spectroscopic data showing onset of predissociation in the B(3)Sigma(u)(-) state,
      as the measurements presented here demonstrate that the long-range correlation of
      the excited state invoked as causing the dissociation is S((3)P(2)) + S((3)P(2))
      rather than S((3)P(2)) + S((3)P(1)). The wavelength dependence of data for the
      S((3)P(2)) + S((3)P(2)) channel suggests involvement of photoexcitation through
      the optically forbidden Herzberg continuum bands in addition to dissociation
      initiated via the optically allowed B(3)Sigma(u)(-)-X(3)Sigma(g)(-) and
      B''(3)Pi(u)-X(3)Sigma(g)(-) bands. Changes in product recoil velocity angular
      distributions and atomic angular momentum polarization were also measured as a
      function of dissociation wavelength. The results are compared with predictions
      from an adiabatic model for dissociation, which provides a basis for
      interpretation but does not explain quantitatively the experimental results.

PMID- 19754092
TI  - Density functional calculation for Li2CuSn as an electrode material for
      rechargeable batteries.
AB  - The all electron full potential linearized augmented plane wave method has been
      used for an ab initio theoretical study of the band structure, density of states
      and electron charge density, and the spectral features of the linear and
      nonlinear optical susceptibilities for the host CuSn and Li(2)CuSn compounds. We
      have calculated the density of states at Fermi energy and the electronic specific
      heat coefficient (gamma). The total charge densities in the (100) and (110)
      planes were calculated. We noticed that inserting Li into CuSn leads to give two
      structures in the spectral features of the linear optical susceptibilities while
      the host compound gives only one structure. Insertion of Li into CuSn leads to
      breaking the symmetry resulting in noncentrosymmetric material. We have
      calculated the complex second-order nonlinear optical susceptibility tensor for
      the intercalated compound.

PMID- 19754093
TI  - Revealing excited state interactions by quantum-chemical modeling of vibronic
      activities: the R2PI spectrum of adenine.
AB  - We present a computational study encompassing quantum-chemical calculations of
      the ground and low-lying excited states of 9H-adenine and modeling of vibronic
      activities associated with the S(0) --> L(b) and S(0) --> n pi* transitions.
      Minima on the ground and excited states and the saddle point on the n pi*
      potential energy surface are determined with CASSCF calculations. Vibrational
      frequencies are computed at the same level of theory on ground and excited states
      while transition dipole moments and oscillator strengths are estimated, at the
      optimized geometries, with CASPT2//CASSCF calculations. Modeling of vibronic
      activities includes both Franck-Condon and Herzberg-Teller induced contributions.
      While the adopted harmonic approximation is acceptable for the S(0) --> L(b)
      transition and allows the assignment of several observed bands in the R2PI
      spectrum of adenine, the computed anharmonic potential along the puckering
      coordinate in the n pi* state requires a different treatment. To this end the
      vibronic levels and intensities associated with vibronic transitions in the
      puckering coordinate are evaluated by numerical solution of the 2D potential
      including the anharmonic puckering coordinate. All the remaining vibrational
      coordinates are treated as harmonic. On the basis of the modeling, the four major
      bands in the R2PI spectrum of adenine are assigned, along with a number of minor
      bands in the spectra.

PMID- 19754094
TI  - Gas-phase acidities of cysteine-polyalanine peptides I: A(3,4)CSH and HSCA(3,4).
AB  - The gas-phase acidities of four cysteine-polyalanine peptides, A(3,4)CSH and
      HSCA(3,4), were determined using the extended Cooks kinetic method with full
      entropy analysis. A triple-quadrupole mass spectrometer with an electrospray
      interface was employed for the experimental study. The ion activation was
      achieved via collision-induced dissociation (CID) experiments. The deprotonation
      enthalpies (Delta(acid)H) of the peptides were determined to be 332.2 +/- 2.0
      kcal/mol (A(3)CSH), 325.9 +/- 2.0 kcal/mol (A(4)CSH), 319.3 +/- 3.0 kcal/mol
      (HSCA(3)), and 319.2 +/- 4.0 kcal/mol (HSCA(4)). The deprotonation entropies
      (Delta(acid)S) of the peptides were estimated based on the entropy term
      (Delta(DeltaS)) and the deprotonation entropies of the reference acids. By using
      the deprotonation enthalpies and entropies, the gas-phase acidities
      (Delta(acid)G) of the peptides were derived: 325.0 +/- 2.0 kcal/mol (A(3)CSH),
      320.2 +/- 2.0 kcal/mol (A(4)CSH), 316.3 +/- 3.0 kcal/mol (HSCA(3)), and 315.4 +/-
      4.0 kcal/mol (HSCA(4)). Conformations and energetic information of the peptides
      were calculated through simulated annealing (Tripos), geometry optimization
      (AM1), and single-point energy calculations (B3LYP/6-31+G(d)), respectively. The
      calculated theoretical deprotonation enthalpies (Delta(acid)H) of 334.2 kcal/mol
      (A(3)CSH), 327.7 kcal/mol (A(4)CSH), 320.6 kcal/mol (HSCA(3)), and 318.6 kcal/mol
      (HSCA(4)) are in good agreement with the experimentally determined values. Both
      the experimental and computational studies suggest that the two N-terminal
      cysteine peptides, HSCA(3,4), are significantly more acidic than the
      corresponding C-terminal ones, A(3,4)CSH. The high acidities of the former are
      likely due to the helical conformational effects for which the thiolate anion may
      be strongly stabilized by the interaction with the helix macrodipole.

PMID- 19754095
TI  - Interaction of isoquinoline alkaloids with an RNA triplex: structural and
      thermodynamic studies of berberine, palmatine, and coralyne binding to
      poly(U).poly(A)(*)poly(U).
AB  - The interaction of two natural protoberberine alkaloids berberine and palmatine
      and the synthetic derivative coralyne with the RNA triplex
      poly(U).poly(A)(*)poly(U) was studied using various biophysical and calorimetric
      techniques. All the three alkaloids bind noncooperatively to the triplex. The
      affinity of berberine and palmatine was in the order of 10(5) M(-1), while that
      of coralyne was one order higher as inferred from spectroscopic studies. The
      alkaloids stabilized the Hoogsteen base-paired third strand of the triplex
      without affecting the stability of the duplex. Fluorescence quenching and
      viscosity studies gave convincing evidence for the partial intercalation of
      berberine and palmatine and a true intercalative binding of coralyne to the
      triplex. This was further supported from the significant polarization of the
      emission spectra of the complex and the energy transfer from the base triplets to
      the alkaloids. Circular dichroic studies suggested that the conformation of the
      triplex was perturbed significantly by the binding of the alkaloids, being more
      by coralyne compared to berberine and palmatine and also evidenced by the
      generation of strong induced optical activity in the bound coralyne molecules.
      Isothermal titration calorimetric studies revealed that the binding to the
      triplex was favored by a predominantly large negative enthalpy change (DeltaH
      degrees = -5.42 kcal/mol) with small favorable entropy contribution (TDeltaS
      degrees = 2.02 kcal/mol) in berberine, favored by almost equal negative enthalpy
      (DeltaH degrees = -3.93 kcal/mol) and entropy changes (TDeltaS degrees = 3.89
      kcal/mol) in palmatine and driven by predominant entropy contributions (DeltaH
      degrees = -1.84 and TDeltaS degrees = 7.44 kcal/mol) in coralyne. These results
      advance our knowledge on the binding of small molecule isoquinoline alkaloids
      that are specific binders of RNA structures, particularly triplexes.

PMID- 19754096
TI  - Ab initio and DFT study of the conformational energy hypersurface of cyclic Gly
      Gly-Gly.
AB  - The multidimensional conformational potential energy hypersurface (PEHS) of
      cyclic Gly-Gly-Gly (1,4,7-triazonane-2,5,8-trione) was comprehensively
      investigated at the Hartree-Fock (RHF/6-31G(d)) level of theory. The equilibrium
      structures, their relative stability, and the transition state (TS) structures
      involved in the conformational interconversion pathways were analyzed. aug-cc
      pVTZ//B3LYP/6-311++G** single point calculations predict a trans-cis-cis
      conformation as the energetically preferred form for this compound. However, all
      of the levels of theory employed here predicted that two forms, a trans-cis-cis
      and a cis-cis-cis (crown), of conformers contribute significantly to the
      equilibrium mixture at room temperature. The conformational interconversion
      between the global minimum and the symmetric cis-cis-cis crown form requires
      12.49 kcal/mol at the RHF 6-31G(d) level of theory, whereas the conformational
      interconversion between the cis-cis-cis crown and cis-cis-cis boat form requires
      18.70 kcal/mol. An exploratory topological analysis of the PEHS was also carried
      out. Our results allow us to form a concise idea about the internal intricacies
      of the PEHSs of these cyclic tripeptides, describing the conformations as well as
      the conformational interconversion processes in these hypersurfaces.

PMID- 19754097
TI  - Mutual influence of cyclopentadienyl and carbonyl ligands in cymantrene: QTAIM
      study.
AB  - The phenomenon of bond length alternation in the cyclopentadienyl (Cp) ligand of
      cymantrene (eta(5)-C(5)H(5))Mn(CO)(3) was investigated using high-resolution X
      ray diffraction analysis (XRD) and quantum chemical calculations. It was shown
      that the trans-effect of strong field CO ligands causes the redistribution of
      electron density in the Cp ring, and it manifests in atomic charges and energy of
      its carbon atoms. The angle C(Cp)-Mn-CO is characteristic for this feature and
      can be used for the prediction of bond lengths and the charge distribution in the
      aromatic fragment in various piano-stool-type complexes.

PMID- 19754098
TI  - Observation of magnetic bistability in polymorphs of the [Ni(dmit)(2)](-)
      complexes.
AB  - Four ion-pair complexes of [Ni(dmit)(2)](-) with [NO(2)bzql](+) have been
      obtained, which belong to two kinds of polymorph forms, [NO(2)bzql][Ni(dmit)(2)]
      (1alpha and 1beta) and [NO(2)bzql][Ni(dmit)(2)].CH(3)COCH(3) (2alpha and 2beta)
      (where dmit = 2-thioxo-1,3-dithiole-4,5-dithiolate and [NO(2)bzql](+) = 1-(4
      nitrobenzyl)quinolinium). Though 1alpha, 2alpha, and 2beta all show anionic
      dimerization structures at room temperature, they have different anionic and
      cationic arrangement fashions, which give rise to different magnetic behaviors
      for these polymorphs or pseudo-polymorphs. Compounds 1alpha, 1beta, and 2alpha
      exhibit magnetic bistabilities. In particular, 1alpha has a hysteretic loop at
      approximately 55 K, while 2beta does not display a spin transition in the 2-300 K
      range. On the basis of the crystal structure data of 2alpha in high- and low
      temperature phases, the magnetic coupling feature within the [Ni(dmit)(2)](-)
      spin dimer was explored with the broken-symmetry approach at the UBPW91/LANL2DZ
      level; combined with the experimental data and theoretical analyses, the
      relationship between the magnetic coupling nature and the stacking pattern of
      [Ni(dmit)(2)](-) anions as well as the origin of the phase interconversion are
      discussed.

PMID- 19754099
TI  - Structural phase transformations of Mg(3)N(2) at high pressure: experimental and
      theoretical studies.
AB  - The structural behavior of Mg(3)N(2) has been investigated up to 40.7 GPa at room
      temperature by means of angle-dispersive X-ray diffraction. A reversible, first
      order structural phase transition from the ambient cubic phase (Ia3) to a high
      pressure monoclinic phase (C2/m) is found to start at approximately 20.6 GPa and
      complete at approximately 32.5 GPa for the first time. The equation of state
      determined from our experiments yields bulk moduli of 110.7(2) and 171.5(1) GPa
      for the cubic and monoclinic phases, respectively, indicating higher
      incompressibility of the high-pressure phase of Mg(3)N(2). First-principles
      calculations reproduced the phase stability and transition pressure determined in
      our experiment. In addition, a second phase transition from the monoclinic phase
      to a hexagonal phase (P3m(1)) was predicted around 67 GPa for Mg(3)N(2). The
      electronic band structures of three phases of Mg(3)N(2) are also calculated and
      discussed.

PMID- 19754100
TI  - Alotamide A, a novel neuropharmacological agent from the marine cyanobacterium
      Lyngbya bouillonii.
AB  - Alotamide A (1), a structurally intriguing cyclic depsipeptide, was isolated from
      the marine mat-forming cyanobacterium Lyngbya bouillonii collected in Papua New
      Guinea. It features three contiguous peptidic residues and an unsaturated
      heptaketide with oxidations and methylations unlike those found in any other
      marine cyanobacterial metabolite. Pure alotamide A (1) displays an unusual
      calcium influx activation profile in murine cerebrocortical neurons with an EC50
      of 4.18 microM.

PMID- 19754101
TI  - X-ray absorption fine structures of uranyl(V) complexes in a nonaqueous solution.
AB  - The structures of three different U(V) complexes, [U(V)O(2)(salophen)DMSO](-),
      [U(V)O(2)(dbm)(2)DMSO](-), and [U(V)O(2)(saldien)](-), in a dimethyl sulfoxide
      (DMSO) solution were determined by X-ray absorption fine structure for the first
      time.

PMID- 19754102
TI  - Development of a disposable microfluidic biochip for multiparameter cell
      population measurements.
AB  - An under recognized cause of preventable mortality is healthcare-associated
      (nosocomial) infections such as biofilms found on implants and catheters. About
      5% of U.S. and E.U. patients acquire nosocomial infections leading to prolonged
      hospitalization, increased patient suffering, and mortality rates. To date, no
      satisfactory solutions are available to monitor biofilm formation under near
      native conditions. As a consequence, in the present work, we report the
      development of a disposable microfluidic biochip capable of continuously
      monitoring cell population dynamics under physiological shear force conditions.
      We demonstrate the simultaneous application of contactless bioimpedance
      spectroscopy and amperometric measurements to monitor fungal biofilm growth rates
      and metabolic activities. Quantitative cell analysis is accomplished by the use
      of high-density interdigitated capacitors (microIDC) isolated by a 700 nm epoxy
      (SU-8 resist) based passivation layer to noninvasively assess biofilm formation
      in predefined proliferation chambers. Additionally, biofilm respiration activity
      is measured using redox-mediators oxidized at band electrodes located downstream
      within microchannels. The disposable biofilm analysis platform is used to
      continuously monitor the dynamic responses of C. albicans to different glucose
      and galactose concentrations.

PMID- 19754103
TI  - Dependence of antimicrobial selectivity and potency on oligomer structure
      investigated using substrate supported lipid bilayers and sum frequency
      generation vibrational spectroscopy.
AB  - Sum frequency generation (SFG) vibrational spectroscopy was used to study
      interactions between solid-supported lipid bilayers mimicking microbial and
      erythrocyte cellular membranes and synthetic antimicrobial arylamide oligomers
      named 2, 3, and 4, designed with the facial amphiphilicity common to naturally
      occurring antimicrobial peptides. The three compounds have the same backbone
      structure but varied side chains. The inherent interfacial sensitivity of SFG
      allowed for simultaneous monitoring of lipid ordering in the individual bilayer
      leaflets and orientation of 2, 3, and 4 upon interaction with the bilayer.
      Critical concentrations at which the inner leaflet is disrupted were determined
      for each oligomer. Spectral evidence of the oligomers' interaction with the
      bilayer below the critical concentrations was also found. Oligomers 2 and 3
      tilted toward the bilayer surface normal, in agreement with previous experimental
      and simulation results. These oligomers selectively interact with microbial
      membrane models over erythrocyte membrane models, correlating well to previously
      published SFG studies on antimicrobial oligomer 1. It was shown that the
      oligomers interact with the lipid bilayers differently, indicating their
      different activity and selectivity. This research further shows that SFG is a
      particularly useful technique for the investigation of interaction mechanisms
      between cell membranes and membrane-active molecules. Additionally, SFG provides
      details of the specific interactions between these novel antimicrobials and lipid
      bilayers.

PMID- 19754104
TI  - Standard-free quantitation of mixtures using clusters formed by electrospray mass
      spectrometry.
AB  - Ion abundances in electrospray ionization mass spectra depend on many factors,
      including molecular hydrophobicity, basicity, solution composition, and
      instrumental parameters. A recently introduced method that uses nonspecific
      cluster ion abundances to obtain solution-phase molar fractions of analytes
      directly from ESI mass spectra without using standards was evaluated using
      solutions containing 0.03-24% L-threonine, D-threonine, L-leucine, L-lysine, L
      glutamic acid, or diglycine with L-serine as a major component. Because of the
      propensity of serine clusters to exhibit "magic" numbers, which can be chirally
      selective, these experiments provide a rigorous test of this standard-free
      cluster quantitation method, which requires that clusters form statistically from
      analytes in solution. For each of these solutions, the compositions of clusters
      containing > or = 32 molecules reflect the solution molar fractions of each
      component. From the abundances of these larger clusters, the solution molar
      fraction can be determined to better than 10% accuracy over nearly 3 orders of
      magnitude in concentration. In contrast, the ionization/detection efficiency of
      the individual amino acids differs by as much as a factor of 460 in these
      experiments. The protonated octamer incorporates some molecules statistically but
      efficiently excludes other molecules that have significantly different properties
      or chirality. This standard-free quantitation method may be most advantageous for
      rapidly characterizing mixtures, such as products of chemical synthesis, which
      contain unknown products or molecules for which suitable standards are not
      readily available.

PMID- 19754105
TI  - Regio- and stereoselective indium triflate-mediated nucleophilic ring-opening
      reactions of 3-aza-2-oxabicyclo[2.2.1]hept-5-ene and -[2.2.2]oct-5-ene systems.
AB  - Indium triflate-mediated nucleophilic ring-opening reactions of 3-aza-2
      oxabicyclo[2.2.1]hept-5-ene and -[2.2.2]oct-5-ene systems with alcohols and water
      were investigated. Reactions of [2.2.1] bicyclic systems gave anti-1,2-, anti-1,4
      and syn-1,4-ring-opened products with moderate to excellent regio- and
      stereoselectivity. When [2.2.2] bicyclic systems were subjected to similar
      reaction conditions, only anti-1,2 and anti-1,4-ring-opened products were
      obtained.

PMID- 19754106
TI  - Heptanosides from galactose-derived oxepenes via stereoselective addition
      reactions.
AB  - Addition reactions to a 3,4-anhydroheptanose gave heptanoside analogues of
      carbohydrate derivatives in good to excellent stereochemical purity.
      Characterization of the products by (1)H and (13)C NMR, COSY, HSQC-DEPT, HMBC, 1D
      TOCSY, and NOE experiments were performed to obtain the stereochemistry of
      addition. The 3,4-anhydroheptanose used in this study is obtained from the ring
      expansion of a cyclopropanated galactal and thus demonstrates the synthetic
      utility of heptanose synthesis via cyclopropanated carbohydrates.

PMID- 19754107
TI  - Direct synthesis of functionalized unsymmetrical beta-sulfonamido disulfides by
      tetrathiomolybdate mediated aziridine ring-opening reactions.
AB  - Direct synthesis of unsymmetrical beta-sulfonamido disulfides by ring-opening of
      aziridines by using benzyltriethyl-ammonium tetrathiomolybdate 1 as a sulfur
      transfer reagent in the presence of symmetrical disulfides as thiol equivalents
      has been reported. Reaction of benzyl and alkyl disulfides gave unsymmetrical
      beta-sulfonamido disulfides as the only product in very good yields. From the
      study, it has been observed that aryl disulfides containing p-NO(2), p-Cl, and p
      CN led to the formation of the corresponding beta-aminosulfides as the exclusive
      products. However, unsubstituted aryl disulfides and the one containing electron
      donating substituents (p-Me) provide a mixture of beta-sulfonamido mono- and
      disulfides as the products.

PMID- 19754108
TI  - Preparation of multisubstituted enamides via rhodium-catalyzed carbozincation and
      hydrozincation of ynamides.
AB  - Rhodium-catalyzed carbozincation of ynamides using diorganozinc reagents or
      functionalized organozinc halides is described. Using a tri(2-furyl)phosphine
      modified rhodium catalyst, the reaction course is altered to hydrozincation when
      diethylzinc is employed as the organozinc reagent. Trapping of the alkenylzinc
      intermediates produced in these reactions in further functionalization reactions
      is possible. Collectively, these processes enable access to a range of
      multisubstituted enamides in stereo- and regiocontrolled fashion.

PMID- 19754109
TI  - A mild method for the efficient [3,3]-sigmatropic rearrangement of N,O
      diacylhydroxylamines.
AB  - A mild, general method for the [3,3]-sigmatropic rearrangement of N,O
      diacylhydroxylamines, employing a combination of mild base and Lewis acid, is
      described. Employing stoichiometric amounts of reagents with respect to substrate
      provides alpha-acyloxyamides, whereas an excess of reagents favors formation of
      cyclic orthoamides.

PMID- 19754110
TI  - Microsecond light-induced proton transfer to flavin in the blue light sensor
      plant cryptochrome.
AB  - Plant cryptochromes are blue light photoreceptors that regulate key responses in
      growth and daily rhythm of plants and might be involved in magnetoreception. They
      show structural homology to the DNA repair enzyme photolyase and bind flavin
      adenine dinucleotide as chromophore. Blue light absorption initiates the
      photoreduction from the oxidized dark state of flavin to the flavin neutral
      radical, which is the signaling state of the sensor. Previous time-resolved
      studies of the photoreduction process have been limited to observation of the
      decay of the radical in the millisecond time domain. We monitored faster, light
      induced changes in absorption of an algal cryptochrome covering a spectral range
      of 375-750 nm with a streak camera setup. Electron transfer from tryptophan to
      flavin is completed before 100 ns under formation of the flavin anion radical.
      Proton transfer takes place with a time constant of 1.7 micros leading to the
      flavin neutral radical. Finally, the flavin radical and a tryptophan neutral
      radical decay with a time constant >200 micros in the millisecond and second time
      domain. The microsecond proton transfer has not been observed in animal
      cryptochromes from insects or photolyases. Furthermore, the strict separation in
      time of electron and proton transfer is novel in the field of flavin-containing
      photoreceptors. The reaction rate implies that the proton donor is not in
      hydrogen bonding distance to the flavin N5. Potential candidates for the proton
      donor and the involvement of the tryptophan triad are discussed.

PMID- 19754111
TI  - Coherent multidimensional optical spectroscopy.

PMID- 19754112
TI  - Vibrational dynamics of hydrogen-bonded complexes in solutions studied with
      ultrafast infrared pump-probe spectroscopy.
AB  - In aqueous solution, the basis of all living processes, hydrogen bonding exerts a
      powerful effect on chemical reactivity. The vibrational energy relaxation (VER)
      process in hydrogen-bonded complexes in solution is sensitive to the microscopic
      environment around the oscillator and to the geometrical configuration of the
      hydrogen-bonded complexes. In this Account, we describe the use of time-resolved
      infrared (IR) pump-probe spectroscopy to study the vibrational dynamics of (i)
      the carbonyl CO stretching modes in protic solvents and (ii) the OH stretching
      modes of phenol and carboxylic acid. In these cases, the carbonyl group acts as a
      hydrogen-bond acceptor, whereas the hydroxyl group acts as a hydrogen-bond donor.
      These vibrational modes have different properties depending on their respective
      chemical bonds, suggesting that hydrogen bonding may have different mechanisms
      and effects on the VER of the CO and OH modes than previously understood. The IR
      pump-probe signals of the CO stretching mode of 9-fluorenone and methyl acetate
      in alcohol, as well as that of acetic acid in water, include several components
      with different time constants. Quantum chemical calculations indicate that the
      dynamical components are the result of various hydrogen-bonded complexes that
      form between solute and solvent molecules. The acceleration of the VER is due to
      the increasing vibrational density of states caused by the formation of hydrogen
      bonds. The vibrational dynamics of the OH stretching mode in hydrogen-bonded
      complexes were studied in several systems. For phenol-base complexes, the decay
      time constant of the pump-probe signal decreases as the band peak of the IR
      absorption spectrum shifts to lower wavenumbers (the result of changing the
      proton acceptor). For phenol oligomers, the decay time constant of the pump-probe
      signal decreases as the probe wavenumber decreases. These observations show that
      the VER time strongly correlates with the strength of hydrogen bonding. This
      acceleration may be due to increased coupling between the OH stretching mode and
      the accepting mode of the VER, because the low-frequency shift caused by hydrogen
      bond formation is very large. Unlike phenol oligomers, however, the pump-probe
      signals of phenol-base complexes did not exhibit probe frequency dependence. For
      these complexes, rapid interconversion between different conformations causes
      rapid fluctuations in the vibrational frequency of the OH stretching modes, and
      these fluctuations level the VER times of different conformations. For the
      benzoic acid dimer, a quantum beat at a frequency of around 100 cm(-1) is
      superimposed on the pump-probe signal. This result indicates the presence of
      strong anharmonic coupling between the intramolecular OH stretching and the
      intermolecular stretching modes. From a two-dimensional plot of the OH stretching
      wavenumber and the low-frequency wavenumber, the wavenumber of the low-frequency
      mode is found to increase monotonically as the probe wavenumber is shifted toward
      lower wavenumbers. Our results represent a quantitative determination of the
      acceleration of VER by the formation of hydrogen bonds. Our studies merit further
      evaluation and raise fundamental questions about the current theory of
      vibrational dynamics in the condensed phase.

PMID- 19754113
TI  - Astrocyte proteins and morphine addiction.

PMID- 19754114
TI  - Mapping the optical properties of CdSe/CdS heterostructure nanocrystals: the
      effects of core size and shell thickness.
AB  - Here we present the first comprehensive report on CdSe/CdS heterostructure
      nanocrystals. The effects of core size and shell thickness on the optical
      properties of CdSe/CdS heterostructure nanocrystals are investigated. We report a
      reliable synthetic method to grow thick CdS shells on CdSe cores with sizes
      ranging from 2.5-4.7 nm. We provide a calibration curve, which enables
      determination of CdS shell thickness (+/-0.1 nm) over a wide range of core sizes,
      circumventing the need for time-consuming HRTEM analyses. Epitaxial growth of the
      shells was verified by HRTEM, XRD, and SAED. In-situ reaction measurements
      revealed the average per particle (p) deposition rates for cadmium and sulfur to
      be k(Cd) = 5.38 x 10(-25) mol s(-1) p(-1) and k(S) = 4.83 x 10(-24) mol s(-1) p(
      1). Faster sulfur deposition rates are attributed to the absence of strong sulfur
      binding ligands in the growth medium. Through the rigorous use of high resolution
      transmission electron microscopy, a direct link between the dimensions of the
      heterostructures and their band-edge transition energies, quantum yields, and
      excited state lifetimes is established. The experiments show that the band-edge
      transition energies of the core samples, which initially span approximately 431
      meV, condense to span only 163 meV after the growth of a 6 monolayer-thick CdS
      shell. Furthermore, shifts in the band-edge transition energies were found to be
      extremely sensitive to core size. The QY of the as-prepared core/shells ranged
      from 25 to 60%. The QYs and band-edge lifetimes of the core/shells were found to
      depend upon the ligands adsorbed to the particle surface. These data prove that
      one or both of the charge carriers still has access to the particle surface
      despite the presence of a 2.2 nm thick CdS shell.

PMID- 19754115
TI  - Development of a merged conjugate addition/oxidative coupling sequence.
      Application to the enantioselective total synthesis of metacycloprodigiosin and
      prodigiosin R1.
AB  - A merged conjugate addition/oxidative coupling sequence that represents an
      efficient strategy for preparing structurally diverse pyrroles has been
      developed. Success of the method hinged upon the controlled oxidative coupling of
      unsymmetrical silyl bis-enol ether intermediates, formed by the 1,4-addition of a
      Grignard reagent with subsequent enolate trapping by a (chloro)silylenol ether.
      The process was applied to the first enantioselective syntheses of the
      biologically active pyrrolophane natural products, metacycloprodigiosin and
      prodigiosin R1.

PMID- 19754116
TI  - EPR and ENDOR characterization of the reactive intermediates in the generation of
      NO by cryoreduced oxy-nitric oxide synthase from Geobacillus stearothermophilus.
AB  - Cryoreduction EPR/ENDOR/step-annealing measurements with substrate complexes of
      oxy-gsNOS (3; gsNOS is nitric oxide synthase from Geobacillus stearothermophilus)
      confirm that Compound I (6) is the reactive heme species that carries out the
      gsNOS-catalyzed (Stage I) oxidation of L-arginine to N-hydroxy-L-arginine (NOHA),
      whereas the active species in the (Stage II) oxidation of NOHA to citrulline and
      HNO/NO(-) is the hydroperoxy-ferric form (5). When 3 is reduced by
      tetrahydrobiopterin (BH4), instead of an externally supplied electron, the
      resulting BH4(+) radical oxidizes HNO/NO(-) to NO. In this report, radiolytic one
      electron reduction of 3 and its complexes with Arg, Me-Arg, and NO(2)Arg was
      shown by EPR and (1)H and (14,15)N ENDOR spectroscopies to generate 5; in
      contrast, during cryoreduction of 3/NOHA, the peroxo-ferric-gsNOS intermediate
      (4/NOHA) was trapped. During annealing at 145 K, ENDOR shows that 5/Arg and 5/Me
      Arg (but not 5/NO(2)Arg) generate a Stage I primary product species in which the
      OH group of the hydroxylated substrate is coordinated to Fe(III), characteristic
      of 6 as the active heme center. Analysis shows that hydroxylation of Arg and Me
      Arg is quantitative. Annealing of 4/NOHA at 160 K converts it first to 5/NOHA and
      then to the Stage II primary enzymatic product. The latter contains Fe(III)
      coordinated by water, characteristic of 5 as the active heme center. It further
      contains quantitative amounts of citrulline and HNO/NO(-); the latter reacts with
      the ferriheme to form the NO-ferroheme upon further annealing. Stage I delivery
      of the first proton of catalysis to the (unobserved) 4 formed by cryoreduction of
      3 involves a bound water that may convey a proton from L-Arg, while the second
      proton likely derives from the carboxyl side chain of Glu 248 or the heme
      carboxylates; the process also involves proton delivery by water(s). In the Stage
      II oxidation of NOHA, the proton that converts 4/NOHA to 5/NOHA likely is derived
      from NOHA itself, a conclusion supported by the pH invariance of the process. The
      present results illustrate how the substrate itself modulates the nature and
      reactivity of intermediates along the monooxygenase reaction pathway.

PMID- 19754117
TI  - Export of methyl parathion hydrolase to the periplasm by the twin-arginine
      translocation pathway in Escherichia coli.
AB  - The uptake of organophosphates (OPs) is a rate-limiting factor in whole-cell
      biocatalysis systems. Here, we report the periplasmic secretion of methyl
      parathion hydrolase (MPH) by employing the twin-arginine translocation (Tat)
      pathway in Escherichia coli. The twin-arginine signal peptide of trimethylamine N
      oxide reductase (TorA) from E. coli was used for exporting MPH to the periplasm
      of E. coli, alleviating the substrate uptake limitation. A periplasmic expression
      vector, pUTM18, coding for TorA-MPH was constructed, and the periplasmic
      secretion and functionality of MPH were demonstrated by cell fractionation,
      immunoblotting, and enzyme activity assays. The strain expressing periplasmic MPH
      showed 3-fold higher whole-cell activity than the control strain expressing
      cytoplasmic MPH. Suspended cultures also exhibited good stability, retaining
      almost 100% activity over a period of 2 weeks. Owing to their high activity and
      superior stability, these "live biocatalysts" are ideal for large-scale
      detoxification of OPs.

PMID- 19754118
TI  - Survey of commercially available chocolate- and cocoa-containing products in the
      United States. 2. Comparison of flavan-3-ol content with nonfat cocoa solids,
      total polyphenols, and percent cacao.
AB  - A survey of a broad range of chocolate- and cocoa-containing products marketed in
      the United States was conducted to provide a more detailed analysis of flavan-3
      ol monomers, oligomers, and polymers, which can be grouped into a class of
      compounds called procyanidins. Samples consisted of the three or four top-selling
      products within the following six categories: natural cocoa powder, unsweetened
      baking chocolate, dark chocolate, semisweet baking chips, milk chocolate, and
      chocolate syrup. Composite samples were characterized for percent fat (% fat),
      percent nonfat cocoa solids (% NFCS), antioxidant level by ORAC, total
      polyphenols, epicatechin, catechin, total monomers, and flavan-3-ol oligomers and
      polymers (procyanidins). On a gram weight basis epicatechin and catechin content
      of the products follow in decreasing order: cocoa powder > baking chocolate >
      dark chocolate = baking chips > milk chocolate > chocolate syrup. Analysis of the
      monomer and oligomer profiles within product categories shows there are two types
      of profiles: (1) products that have high monomers with decreasing levels of
      oligomers and (2) products in which the level of dimers is equal to or greater
      than the monomers. Results show a strong correlation (R(2) = 0.834) of
      epicatechin to the level of % NFCS and also very good correlations for N = 2-5
      oligomers to % NFCS. A weaker correlation was observed for catechin to % NFCS
      (R(2) = 0.680). Other analyses show a similar high degree of correlation with
      epicatechin and N = 2-5 oligomers to total polyphenols, with catechin being less
      well correlated to total polyphenols. A lesser but still good correlation exists
      between the calculated percent cacao (calcd % cacao) content, a proxy for percent
      cacao, and these same flavanol measures, with catechin again showing a lesser
      degree of correlation to calcd % cacao. Principal component analysis (PCA) shows
      that the products group discretely into five classes: (1) cocoa powder, (2)
      baking chocolate, (3) dark chocolate and semisweet chips, (4) milk chocolates,
      and (5) syrup. PCA also shows that most factors group closely together including
      the antioxidant activity, total polyphenols, and the flavan-3-ol measures with
      the exception of catechin and % fat in the product, which group separately.
      Because catechin distribution appears to be different from the other flavan-3-ol
      measures, an analysis of the epicatechin to catechin ratio was done, indicating
      there is a >5-fold variation in this measure across the products studied. The
      cocoa-containing products tested range from cocoa powder with 227.34 +/- 17.23 mg
      of procyanidins per serving to 25.75 +/- 9.91 mg of procyanidins per serving for
      chocolate syrup. These results are discussed with respect to other studies on
      commercial products, the bioavailability of the flavanols, and the possible role
      of processing on the amount of catechin in products.

PMID- 19754119
TI  - Phloroglucinols inhibit chemical mediators and xanthine oxidase, and protect
      cisplatin-induced cell death by reducing reactive oxygen species in normal human
      urothelial and bladder cancer cells.
AB  - Phloroglucinols, garcinielliptones HA-HE (1-5), and C (6) were studied in vitro
      for their inhibitory effects on chemical mediators released from mast cells,
      neutrophils, and macrophages. Compound 6 revealed significant inhibitory effect
      on release of lysozyme from rat neutrophils stimulated with formyl-Met-Leu-Phe
      (fMLP)/cytochalasin B (CB). Compounds 3, 4, and 6 showed significant inhibitory
      effects on superoxide anion generation in rat neutrophils stimulated with
      (fMLP)/(CB), while compounds 1 and 5 revealed inhibitory effects on tumor
      necrosis factor-alpha (TNF-alpha) formation in macrophages stimulated with
      lipopolysaccharide (LPS). Compounds 1 and 3-6 showed inhibitory effects on
      xanthine oxidase (XO) and could inhibit the DNA breakage caused by O2(-*).
      Treatment of NTUB1 with 2 to 60 microM compound 3 and 5 microM cisplatin and SV
      HUC1 with 9 to 60 microM 3 and 5 microM cisplatin, respectively, resulted in an
      increase of viability of cells. These results indicated that compounds 1 and 3-6
      showed anti-inflammatory effects and antioxidant activities. Compound 3 mediates
      through the suppression of XO activity and reduction of reactive oxygen species
      (ROS), and protection of subsequent cell death.

PMID- 19754120
TI  - Oxidation of cholesterol and beta-sitosterol and prevention by natural
      antioxidants.
AB  - Consumption of cholesterol oxidation products (COPs) is a growing health concern,
      but little is known about the intake of beta-sitosterol oxidation products
      (SOPs). The present study was performed (i) to compare the oxidative stability of
      cholesterol with that of beta-sitosterol; (ii) to investigate the oxidative
      pattern of cholesterol and beta-sitosterol in lard, corn oil, and olive oil; and
      (iii) to examine the effectiveness of green tea catechins (GTC), alpha
      tocopherol, and quercetin in prevention of cholesterol and beta-sitosterol
      oxidation compared with butylated hydroxytoluene (BHT). Results showed both
      cholesterol and beta-sitosterol were thermally unstable with 75% of cholesterol
      and beta-sitosterol being oxidized at 180 degrees C for 2 h. The oxidation
      behavior of beta-sitosterol was similar to that of cholesterol in terms of
      oxidative rate and oxidation products. The major COPs produced were 7
      ketocholesterol, 7alpha-hydroxycholesterol, 7beta-hydroxycholesterol 5,6alpha
      epoxycholesterol, and 5,6beta-epoxycholesterol, whereas the major SOPs were 7
      ketositosterol, 7alpha-hydroxysitosterol, 7beta-hydroxysitosterol, 5,6alpha
      epoxysitosterol, and 5,6beta-epoxysitosterol. Under the same experimental
      conditions, both cholesterol and beta-sitosterol were oxidized more slowly in
      corn oil, lard, and olive oil, attributable to the unsaponified antioxidants
      present in these fat and oils. GTC, alpha-tocopherol, and quercetin were more
      effective than BHT in preventing the oxidation of cholesterol and beta
      sitosterol.

PMID- 19754121
TI  - Synthesis and characterization of degradable polar hydrophobic ionic polyurethane
      scaffolds for vascular tissue engineering applications.
AB  - In tissue engineering, the ability to manipulate scaffold design characteristics
      is important to achieve functional tissue regeneration. In this study, degradable
      polar hydrophobic ionic polyurethane (D-PHI) porous scaffolds were synthesized
      using a lysine-based divinyl oligomer (DVO). Optimization studies on the DVO and
      D-PHI scaffold synthesis were conducted to maximize isocyanate and methacrylate
      monomer conversion, respectively. D-PHI scaffold properties were manipulated
      through the introduction of a lysine-based cross-linker. Specifically, increasing
      D-PHI cross-linker concentration resulted in an increase of the elastic modulus
      (0.5-21 MPa), a decrease of the elongation-at-yield (45-5%) and a reduction of
      scaffold swelling (170-100%). Based on a preliminary study with A10 vascular
      smooth muscle cells, D-PHI scaffolds demonstrated the ability to support cell
      adhesion and growth during 2 weeks of culture, suggesting their potential
      suitability for longer term vascular tissue engineering. The versatility of the D
      PHI properties may allow for the tailoring of cell-material interaction and
      ultimately functional tissue regeneration.

PMID- 19754122
TI  - Structure and properties of silicified purple membrane thin films.
AB  - Electrodeposited or evaporated thin films of purple membrane (PM) sheets
      comprising close packed arrays of bacteriorhodopsin demonstrate enhanced chemical
      stability and retention of photochromic and photovoltaic behavior when
      periodically intercalated with nanothin layers of aminopropyl-functionalized
      silica. In contrast, hybrid composites prepared from PM films infiltrated with
      nonorgano-functionalized silica are structurally nonintegrated, prone to
      cracking, and exhibit no photochromic or photoelectric properties. The results
      indicate that the presence of the aminopropyl functionality in the silica matrix
      facilitates formation of the intercalated nanostructure, increases the rates of B
      state recovery and M-state decay in the photocycle, and enhances the photovoltage
      response. Changes in photoactivity suggest that the aminopropyl moiety acts as a
      strong proton donor/acceptor when intercalated between PM sheets. The ability to
      fabricate hybrid thin films of electrophoretically oriented PM sheets with
      enhanced physical and chemical properties could be important in the design of
      novel components for bacteriorhodopsin-based applications.

PMID- 19754123
TI  - Aggregation kinetics of macrocycles detected by magnetic birefringence.
AB  - We have used magnetic-field-induced birefringence as a new sensitive technique to
      probe the aggregation kinetics of macrocyclic molecules in solution. We have
      found three consecutive aggregation stages: disordered objects, ordered fibers,
      and a network. The transition from disordered objects to ordered fibers is found
      to be slow, taking days or weeks to complete. We attribute this to the molecular
      tails of the macrocycles, which hamper fiber formation. We anticipate that
      linking aggregation kinetics to molecular properties will lead to a better
      understanding of the mechanisms by which molecules self-assemble, allowing for a
      more rational design of the molecular building blocks.

PMID- 19754124
TI  - Thermodynamic studies and hydride transfer reactions from a rhodium complex to
      BX3 compounds.
AB  - This study examines the use of transition-metal hydride complexes that can be
      generated by the heterolytic cleavage of H(2) gas to form B-H bonds.
      Specifically, these studies are focused on providing a reliable and quantitative
      method for determining when hydride transfer from transition-metal hydrides to
      three-coordinate BX(3) (X = OR, SPh, F, H; R = Ph, p-C(6)H(4)OMe, C(6)F(5),
      (t)Bu, Si(Me)(3)) compounds will be favorable. This involves both experimental
      and theoretical determinations of hydride transfer abilities. Thermodynamic
      hydride donor abilities (DeltaG(o)(H(-))) were determined for HRh(dmpe)(2) and
      HRh(depe)(2), where dmpe = 1,2-bis(dimethylphosphinoethane) and depe = 1,2
      bis(diethylphosphinoethane), on a previously established scale in acetonitrile.
      This hydride donor ability was used to determine the hydride donor ability of
      [HBEt(3)](-) on this scale. Isodesmic reactions between [HBEt(3)](-) and selected
      BX(3) compounds to form BEt(3) and [HBX(3)](-) were examined computationally to
      determine their relative hydride affinities. The use of these scales of hydride
      donor abilities and hydride affinities for transition-metal hydrides and BX(3)
      compounds is illustrated with a few selected reactions relevant to the
      regeneration of ammonia borane. Our findings indicate that it is possible to form
      B-H bonds from B-X bonds, and the extent to which BX(3) compounds are reduced by
      transition-metal hydride complexes forming species containing multiple B-H bonds
      depends on the heterolytic B-X bond energy. An example is the reduction of
      B(SPh)(3) using HRh(dmpe)(2) in the presence of triethylamine to form Et(3)N
      BH(3) in high yields.

PMID- 19754125
TI  - Periodic mesoporous organosilica with a hexagonally pillared lamellar structure.
AB  - Ordered mesoporous materials (OMMs) with well-defined pore sizes (>2 nm) and pore
      geometries are important in various applications that require fast mass transfer
      or deal with large molecules. Extensive research has resulted in the discovery of
      OMMs with three types of mesostructures: (i) bi- or multicontinuous, (ii)
      columnar, and (iii) discontinuous (cagelike). However, another type, the pillared
      lamellar structure, which has long been sought and has been mathematically
      computed and known to exist in the research fields of surfactant and multiblock
      copolymer mesophases, still remains a mesostructure that has not been observed in
      real OMMs for any specific symmetry. Herein, we report an unprecedented type of
      ordered mesoporous material with a hexagonally pillared lamellar (HPL) structure
      (P6(3)/mmc) that can be synthesized via a phase transformation from a lamellar
      mesophase by hydrothermal reaction in the presence of an organosilica precursor
      and a high concentration of a designed Gemini surfactant (Gem(16-3-16)) that has
      a large g value. The present GMO-HPL, which has an unique three-dimensional
      periodic structure with two-dimensionally connected pore channels running between
      the framework layers, provides a fascinating topological link between the
      lamellar and columnar (2D hexagonal) mesophases. It is unique in its application
      potential by making possible selective 2D diffusion in different directions.

PMID- 19754126
TI  - Origin of enantioselectivity in the Jacobsen epoxidation of olefins.
AB  - It is proposed that facial selectivity in the Jacobsen epoxidation is determined
      by electrostatic and steric factors with a two-step pathway involving a
      carbocationic intermediate.

PMID- 19754127
TI  - Porphyrin intercalation in G4-DNA quadruplexes by molecular dynamics simulations.
AB  - We investigated the intercalation of a porphyrin derivative (TMPyP) between
      guanine tetrads (G4-tetrads, G4t's) in 4-stranded G4-DNA oligomers by classical
      molecular dynamics simulations. Contrary to experimental evidence on very short
      oligomers that contain stabilizing cations, we find that TMPyP can stack with the
      G4-tetrads in the absence of interplane cations. A high TMPyP/G4t stoichiometric
      ratio of 1/2 induces strong deformations of the G4-quadruplexes. A lower ratio of
      1/8 is better compatible with the helical conformation. When a TMPyP is
      accommodated between two tetrads, the stacking distance between the intercalated
      molecule and a G4-tetrad is approximately 4.3-4.7 A. We find that the possibility
      of regular TMPyP intercalation depends on the length of the quadruplex, on the
      stoichiometric ratio and on the edge termination motif.

PMID- 19754128
TI  - Cassiarins C-E, antiplasmodial alkaloids from the flowers of Cassia siamea.
AB  - Three new alkaloids, cassiarins C-E (1-3), and a new chromone, 10,11
      dihydroanhydrobarakol (4), which showed moderate antiplasmodial activity against
      Plasmodium falciparum 3D7, were isolated from flowers of Cassia siamea, and the
      structures of 1-4 were elucidated by 2D NMR analysis and chemical transformation.
      Cassiarin D (2) was a dimeric compound consisting of 5-acetonyl-7-hydroxy-2
      methylchromone and cassiarin C (1), and cassiarin E (3) was a dimer of cassiarins
      A and C (1).

PMID- 19754129
TI  - Inactivation of epidermal growth factor receptor and downstream pathways in oral
      squamous cell carcinoma Ca9-22 cells by cardiotoxin III from Naja naja atra.
AB  - Cardiotoxin III (1), a basic polypeptide with 60 amino acid residues isolated
      from Naja naja atra venom, has potential therapeutic activity in cancer.
      Treatment with 1 reduced phosphorylation of EGFR and Akt, as well as ERK in Ca9
      22 cells. Moreover, 1-treatment inhibited constitutive activation of STAT3 and
      STAT5 in a time-dependent manner. Up-regulation of Bax and down-regulation of
      anti-apoptotic proteins including Bcl-2, Bcl-X(L), and myeloid cell leukemia
      1(Mcl-1) were also found in cells treated with 1. In addition, 1-treatment
      disrupted mitochondrial membrane potential (DeltaPsim) and resulted in release of
      mitochondrial cytochrome c and activation of both caspases-9 and -3. AG1478, a
      specific pharmacological inhibitor of EGFR activation, mimics the cytotoxic
      effects of 1. Taken together, these results showed that 1 causes significant
      induction of apoptosis in Ca9-22 cells via abolition of the EGFR-mediated
      survival pathway of these cells. Thus, cardiotoxin III appears to be a potential
      therapeutic agent for killing oral squamous carcinoma Ca9-22 cells.

PMID- 19754130
TI  - Cytotoxic compounds from the stems of Cinnamomum tenuifolium.
AB  - Three new butanolides, tenuifolide A (1), isotenuifolide A (2), and tenuifolide B
      (3), a new secobutanolide, secotenuifolide A (4), and one new sesquiterpenoid,
      tenuifolin (5), along with 16 known compounds were isolated from the stems of
      Cinnamomum tenuifolium. Their structures were determined by spectroscopic
      analyses. Compound 4 was found to induce apoptotic-related DNA damage, increase
      sub-G1 cells, and inhibit the growth of human prostate cancer cells, DU145. In
      addition, treatment with 4 significantly increased intracellular H2O2 and/or
      peroxide. The results show that 4 induced (a) noticeable reduction of
      mitochondrial transmembrane potential (DeltaPsim); (b) significant increase in
      the ratio of cytochrome c concentration (cytosol/mitochondria); and (c)
      subsequent activation of caspase-9/caspase-3. Antiproliferation caused by 4 was
      found to markedly decrease when pretreated with caspase-9/caspase-3 inhibitor. In
      ROS scavenging, antioxidant, NADPH oxidase, and NO inhibitor studies,
      pretreatment of DU145 cells with either DPI, dexamethasone, L-NAME, or mannitol
      decreased 4-induced intracellular DCF fluorescence of ROS. These results suggest
      that an increase of H2O2 and/or peroxide by 4 is the initial apoptotic event and
      4 has anticancer effects on DU145 cells.

PMID- 19754131
TI  - Interaction of gold nanoparticles in barium titanate thin films.
AB  - A novel approach to control the grain size of oxide thin film materials has been
      investigated. Perovskite BaTiO(3) shows interesting grain structures when
      deposited on gold predeposited, (111)-oriented, single-crystal SrTiO(3)
      substrates. Solid oxide films grow epitaxially on patterned seed layers and show
      variations in grain size relative to the films deposited on SrTiO(3) directly.

PMID- 19754132
TI  - Electrowetting control of Cassie-to-Wenzel transitions in superhydrophobic carbon
      nanotube-based nanocomposites.
AB  - The possibility of effective control of the wetting properties of a
      nanostructured surface consisting of arrays of amorphous carbon nanoparticles
      capped on carbon nanotubes using the electrowetting technique is demonstrated. By
      analyzing the electrowetting curves with an equivalent circuit model of the
      solid/liquid interface, the long-standing problem of control and monitoring of
      the transition between the "slippy" Cassie state and the "sticky" Wenzel states
      is resolved. The unique structural properties of the custom-designed
      nanocomposites with precisely tailored surface energy without using any commonly
      utilized low-surface-energy (e.g., polymer) conformal coatings enable easy
      identification of the occurrence of such transition from the optical contrast on
      the nanostructured surfaces. This approach to precise control of the wetting mode
      transitions is generic and has an outstanding potential to enable the stable
      superhydrophobic capability of nanostructured surfaces for numerous applications,
      such as low-friction microfluidics and self-cleaning.

PMID- 19754133
TI  - Local probe oxidation of self-assembled monolayers on hydrogen-terminated
      silicon.
AB  - Local probe oxidation experiments by conductive AFM have been performed on a
      hexadecyl monolayer and a N-hydroxysuccinimide (NHS)-ester-functionalized undecyl
      (NHS-UA) monolayer assembled on hydrogen-terminated (i.e., unoxidized) silicon.
      The oxidation conditions for the mild oxidation of the top terminal groups of
      monolayers and the deep oxidation of the underlying silicon into silicon oxide
      were investigated. The results show that the bias threshold for the AFM tip
      induced oxidation of the top groups of monolayers on oxide-free silicon can be
      reduced by 2 V for the methyl-terminated hexadecyl monolayer and even by 3.5 V
      for the active NHS-ester-terminated undecyl monolayer, in comparison to a methyl
      terminated octadecyl trichlorosilane (OTS) monolayer on oxidized silicon. Upon
      such local mild oxidation, the active NHS ester group of the NHS-UA monolayer is
      selectively cleaved off to generate carboxyl-containing monolayer nanopatterns,
      opening further possibilities for subsequent patterned multifunctionalization.

PMID- 19754134
TI  - Concentration state dependence of the rheological and structural properties of
      reconstituted silk.
AB  - The ability to control the processing of artificial silk is key to the successful
      application of this important and high performance biopolymer. Understanding
      where our current reconstitution process can be improved will not only aid us in
      the creation of better materials, but will also provide insight into the natural
      material along the way. This study aims to understand what proportion of
      reconstituted silk contributes to its rheological properties and what
      conformational state the silk proteins are in. It shows, for the first time, that
      a change in rheological properties can be related to a change in silk structures
      present in solution and reveals a low concentration gel state for silk that may
      have important implications for future successful artificial processing of silk.

PMID- 19754135
TI  - Synthesis of (13)C-perlabeled cellulose with more than 99% isotopic enrichment by
      a cationic ring-opening polymerization approach.
AB  - (13)C-Perlabeled cellulose was obtained in a seven-step approach from (13)C(6)
      labeled d-glucose with a cationic ring-opening polymerization as the key step.
      Isopropylidene protection, benzylation of the remaining free 3-O-position and
      subsequent deprotection afforded 3-O-benzyl-(13)C(6)-glucose (2). Regioselective
      bis-pivaloylation followed by subsequent ortho-esterification provided the
      precursor for the cationic ring-opening polymerization, 3-O-benzyl-(13)C(6)
      glucopyranose 1,2,4-orthopivalate (4). The actual polymerization step gave a
      stereo- and regioregular (13)C-perlabeled (1-->4)-beta-glucopyranan derivative,
      which was deprotected into fully labeled (13)C-cellulose, as the cellulose II
      allomorph with a DP of 40, in an overall 28% yield. All reaction steps were
      optimized beforehand with nonlabeled compounds toward high yields and high
      reproducibility and the final compound was comprehensively analytically
      characterized.

PMID- 19754136
TI  - Structural constraints imposed by the conserved fusion peptide on the HIV-1 gp41
      epitope recognized by the broadly neutralizing antibody 2F5.
AB  - The HIV-1 gp41 epitope recognized by the broadly neutralizing 2F5 antibody has
      focused much attention as a suitable target in the design of peptide immunogens.
      Peptides mimicking the linear 2F5 epitope (2F5ep) are however intrinsically
      disordered, while the structural constraints existing in the cognate gp41 native
      structure recognized by the antibody are presently unknown. In recent reports, we
      have shown that core residues of the amino-terminal fusion peptide (FP) increase
      MAb2F5 affinity. Here, we have inferred the sequence-specific structural
      constraints imposed by the FP residues on the 2F5 epitope from the comparison of
      two hybrid peptides: HybK3, which connects through a flexible tether residues
      derived from 2F5ep and FP sequences, and scrHybK3, combining 2F5ep and an FP
      sequence with the conserved core scrambled. Circular dichroism, conventional and
      two-dimensional correlation infrared spectroscopy, and X-ray diffraction studies
      revealed specific structural features that were dependent on the exact FP
      sequence, namely, (i) the production with moderate low polarity of an
      intermediate folded structure enriched in beta-turns and alpha-helix; (ii) the
      existence in this intermediate of a thermotropic conformational transition taking
      place at ca. 18-20 degrees C, consistent with the conversion of 3(10)-helices
      into beta-turn conformers; and (iii) the presence of a C-terminal alpha-helix in
      crystals of Fab'-peptide complexes. Those features support the existence of
      native-like tertiary interactions between FP and 2F5 epitope residues, which
      might be important to recreate when developing an effective AIDS peptide vaccine.

PMID- 19754137
TI  - Dimensionality of diffusive exploration at the protein interface in solution.
AB  - The dynamics of water are critically important to the energies of interaction
      between proteins and substrates and determine the efficiency of transport at the
      interface. The magnetic field dependence of the nuclear spin-lattice relaxation
      rate constant 1/T(1) of water protons provides a direct characterization of water
      diffusional dynamics at the protein interface. We find that the surface-average
      translational correlation time is 30-40 ps and the magnetic field dependence of
      the water proton 1/T(1) is characteristic of two-dimensional diffusion of water
      in the protein interfacial region. The reduced dimensionality substantially
      increases the intermolecular re-encounter probability and the efficiency of the
      surface exploration by the small molecule, water in this case. We propose a
      comprehensive theory of the translational effects of a small diffusing particle
      confined in the vicinity of a spherical macromolecule as a function of the
      relative size of the two particles. We show that the change in the apparent
      dimensionality of the diffusive exploration is a general result of the small
      diffusing particle encountering a much larger particle that presents a diffusion
      barrier. Examination of the effects of the size of the confinement relative to
      the macromolecule size reveals that the reduced dimensionality characterizing the
      small-molecule diffusion persists to remarkably small radius ratios. The
      experimental results on several different proteins in solution support the
      proposed theoretical model, which may be generalized to other small-particle
      large-body systems like vesicles and micelles.

PMID- 19754138
TI  - Iron uptake and transport in plants: the good, the bad, and the ionome.

PMID- 19754139
TI  - Molecular dynamics study of the structure and interparticle interactions of
      polyethylene glycol-conjugated PAMAM dendrimers.
AB  - We performed molecular dynamics (MD) simulations of one or two copies of
      polyethylene glycol of molecular weight 550 (PEG550) and 5000 (PEG5000) daltons,
      conjugated to generation 3 (G3) to 5 (G5) polyamidoamine (PAMAM) dendrimers with
      explicit water using a coarse-grained model. We found the radii of gyration of
      these dendrimer-PEG molecules to be close to those measured in experiments by
      Hedden and Bauer (Hedden , R. C. ; Bauer , B. J. Macromolecules 2003 , 36 ,
      1829.). Densely grafted PEG ligands (>50% of the dendrimer surface) extend like
      brushes, with layer thickness in agreement with theory for starlike polymers. Two
      dendrimer-PEG complexes in the box drift away from each other, indicating that no
      aggregation is induced by either short or long PEG chains, conflicting with a
      recent view that the cytotoxicity of some PEGylated particles might be due to
      particle aggregation for long PEG lengths.

PMID- 19754140
TI  - Effective electrochemical method for investigation of hemoglobin unfolding based
      on the redox property of heme groups at glassy carbon electrodes.
AB  - This study demonstrates a facile and effective electrochemical method for
      investigation of hemoglobin (Hb) unfolding based on the electrochemical redox
      property of heme groups in Hb at bare glassy carbon (GC) electrodes. In the
      native state, the heme groups are deeply buried in the hydrophobic pockets of Hb
      with a five-coordinate high-spin complex and thus show a poor electrochemical
      property at bare GC electrodes. Upon the unfolding of Hb induced by the
      denaturant of guanidine hydrochloride (GdnHCl), the fifth coordinative bond
      between the heme groups and the residue of the polypeptides (His-F8) is broken,
      and as a result, the heme groups initially buried deeply in the hydrophobic
      pockets dissociate from the polypeptide chains and are reduced electrochemically
      at GC electrodes, which can be used to probe the unfolding of Hb. The results on
      the GdnHCl-induced Hb unfolding obtained with the electrochemical method
      described here well coincide with those studied with other methods, such as UV
      vis spectroscopy, fluorescence, and circular dichroism. The application of the as
      established electrochemical method is illustrated to study the kinetics of GdnHCl
      induced Hb unfolding, the GdnHCl-induced unfolding of another kind of
      hemoprotein, catalase, and the pH-induced Hb unfolding/refolding.

PMID- 19754141
TI  - Controlled self-assembly of electron donor nanotubes.
AB  - We employ a combination of urea-urea hydrogen bonds and pi-pi stacking
      interactions to obtain soluble self-assembled nanotubes decorated with electron
      donor TTF derivatives on the periphery. We have investigated the structure and
      stability of the nanotubes with a combination of experiments and high-level DFT
      calculations. We also demonstrate that the association process can be controlled
      by changes in the hydrogen-bonding ability of the solvent and electrochemically.

PMID- 19754143
TI  - Highly efficient interfacing of guided plasmons and photons in nanowires.
AB  - Successful exploitations of strongly confined surface plasmon-polaritons
      critically rely on their efficient and rapid conversion to lossless channels. We
      demonstrate a simple, robust, and broadband butt-coupling technique for
      connecting a metallic nanowire and a dielectric nanofiber. Conversion
      efficiencies above 95% in the visible and close to 100% in the near-infrared can
      be achieved with realistic parameters. Moreover, by combining butt-coupling with
      nanofocusing, we propose a broadband high-throughput near-field optical
      microscope.

PMID- 19754142
TI  - Molecular dynamics and quantum mechanics of RNA: conformational and chemical
      change we can believe in.
AB  - Structure and dynamics are both critical to RNA's vital functions in biology.
      Numerous techniques can elucidate the structural dynamics of RNA, but
      computational approaches based on experimental data arguably hold the promise of
      providing the most detail. In this Account, we highlight areas wherein molecular
      dynamics (MD) and quantum mechanical (QM) techniques are applied to RNA,
      particularly in relation to complementary experimental studies. We have expanded
      on atomic-resolution crystal structures of RNAs in functionally relevant states
      by applying explicit solvent MD simulations to explore their dynamics and
      conformational changes on the submicrosecond time scale. MD relies on simplified
      atomistic, pairwise additive interaction potentials (force fields). Because of
      limited sampling, due to the finite accessible simulation time scale and the
      approximated force field, high-quality starting structures are required. Despite
      their imperfection, we find that currently available force fields empower MD to
      provide meaningful and predictive information on RNA dynamics around a
      crystallographically defined energy minimum. The performance of force fields can
      be estimated by precise QM calculations on small model systems. Such calculations
      agree reasonably well with the Cornell et al. AMBER force field, particularly for
      stacking and hydrogen-bonding interactions. A final verification of any force
      field is accomplished by simulations of complex nucleic acid structures. The
      performance of the Cornell et al. AMBER force field generally corresponds well
      with and augments experimental data, but one notable exception could be the
      capping loops of double-helical stems. In addition, the performance of pairwise
      additive force fields is obviously unsatisfactory for inclusion of divalent
      cations, because their interactions lead to major polarization and charge
      transfer effects neglected by the force field. Neglect of polarization also
      limits, albeit to a lesser extent, the description accuracy of other
      contributions, such as interactions with monovalent ions, conformational
      flexibility of the anionic sugar-phosphate backbone, hydrogen bonding, and solute
      polarization by solvent. Still, despite limitations, MD simulations are a valid
      tool for analyzing the structural dynamics of existing experimental structures.
      Careful analysis of MD simulations can identify problematic aspects of an
      experimental RNA structure, unveil structural characteristics masked by
      experimental constraints, reveal functionally significant stochastic
      fluctuations, evaluate the structural role of base ionization, and predict
      structurally and potentially functionally important details of the solvent
      behavior, including the presence of tightly bound water molecules. Moreover,
      combining classical MD simulations with QM calculations in hybrid QM/MM
      approaches helps in the assessment of the plausibility of chemical mechanisms of
      catalytic RNAs (ribozymes). In contrast, the reliable prediction of structure
      from sequence information is beyond the applicability of MD tools. The ultimate
      utility of computational studies in understanding RNA function thus requires that
      the results are neither blindly accepted nor flatly rejected, but rather
      considered in the context of all available experimental data, with great care
      given to assessing limitations through the available starting structures, force
      field approximations, and sampling limitations. The examples given in this
      Account showcase how the judicious use of basic MD simulations has already served
      as a powerful tool to help evaluate the role of structural dynamics in biological
      function of RNA.

PMID- 19754144
TI  - Freeze-dried grape powder attenuates mitochondria- and oxidative stress-mediated
      apoptosis in liver cells.
AB  - The beneficial effects of grape consumption have been attributed to the
      antioxidant activity of its polyphenols. This study was conducted to investigate
      the cytoprotective effects of a freeze-dried grape powder (FDGP) on liver cells.
      FDGP treatment of primary hepatocytes and hepatoma cells revealed increased
      metabolic activity of cells and phosphorylation of Akt and IkappaBalpha, as well
      as up-regulation of proliferating cell nuclear antigen (PCNA) level. To study the
      molecular mechanisms of FDGP effects, cells were treated with TNF-related
      apoptosis-inducing ligand (TRAIL); taurodeoxycholic acid (TDCA); thapsigargin
      (TG), to induce cell apoptosis through death receptor-, mitochondria-, or ER
      mediated pathway; and H(2)O(2), to induce oxidative stress, respectively. TDCA
      induced activation of caspase-3, caspase-7, caspase-9, and Bax was dramatically
      decreased with cotreatment of FDGP. Furthermore, FDGP reduced levels of annexin V
      positive cells by 4-fold. Also, FDGP pretreatment restored cellular glutathione
      content by 71% in cells treated with H(2)O(2). However, FDGP did not inhibit ER
      mediated apoptosis. In conclusion, FDGP increased the viability and metabolic
      activity of liver cells and attenuated oxidative stress- and mitochondria
      mediated apoptosis. These data may contribute to the understanding of the
      mechanisms involved in protective effects of grape in a variety of liver
      conditions associated with cellular stress.

PMID- 19754145
TI  - Second generation synthesis of C27-C35 building block of E7389, a synthetic
      halichondrin analogue.
AB  - A practical method is reported to synthesize E7389 C27-C35 building block 13 from
      1,2-O-isopropylidene-alpha-D-5-deoxyglucurono-6,3-lactone (3). This synthesis
      relies on two key processes: (1) C34/C35-diol is introduced via asymmetric
      dihydroxylation with dr = 3:1, with the undesired C34-diastereomer effectively
      removed by crystallization of 11, and (2) the C30 PhSO2CH2 group is introduced
      stereoselectively (>100:1) via hydrogenation of 12 in the presence of the
      Crabtree catalyst. The reported synthesis is practically free from
      chromatographic separation.

PMID- 19754146
TI  - Quantitation of S-methylmethionine in raw vegetables and green malt by a stable
      isotope dilution assay using LC-MS/MS: comparison with dimethyl sulfide formation
      after heat treatment.
AB  - The potent odorant dimethyl sulfide (1), showing a low odor threshold of 0.12
      microg/L in water, is known to contribute to the aromas of various foods. Its
      cabbage-like odor plays an important role, particularly, in cooked vegetables,
      such as cabbage, celery, or asparagus. On the other hand, in fruit juices or
      beer, 1 may generate off-flavors. S-Methylmethionine (2) has previously been
      characterized as precursor of 1 during thermal processing, and several methods
      for its quantitation have been proposed. Using deuterium-labeled 2 as the
      internal standard, a stable isotope dilution assay (SIDA) using LC-MS/MS was
      developed for the fast quantitation of 2 in vegetables and malt. Application of
      the method to different foods revealed amounts between 2.8 mg (fresh tomatoes)
      and 176 mg (celery) of 2 per kilogram. To correlate the amount of 1 formed upon
      processing with the amounts of 2 present in the raw material, 1 was quantified
      before and after a thermal treatment of the same raw materials by a SIDA.
      Concentrations between 1.1 mg/kg (fresh tomatoes) and 26 mg/kg (celery) were
      determined in the processed samples. The quantitation of 2 during steeping,
      germination, and malting of barley, and a correlation of the data with the
      amounts of 1 formed after thermal treatment of the malt, resulted in yields
      between 24 and 27 mol % calculated on the basis of the amounts of 2. The results
      suggested that the extent of the formation of 1 can be predicted, for example, in
      plant materials, from the amount of 2 present in the raw foods.

PMID- 19754147
TI  - Assessing the occurrence and distribution of pyrethroids in water and suspended
      sediments.
AB  - The distribution of pyrethroid insecticides in the environment was assessed by
      separately measuring concentrations in the dissolved and suspended sediment
      phases of surface water samples. Filtered water was extracted by HLB solid-phase
      extraction cartridges, while the sediment on the filter was sonicated and cleaned
      up using carbon and aluminum cartridges. Detection limits for the 13 pyrethroids
      analyzed by gas chromatography-tandem mass spectrometry were 0.5 to 1 ng L(-1)
      for water and 2 to 6 ng g(-1) for the suspended sediments. Seven pyrethroids were
      detected in six water samples collected from either urban or agricultural creeks,
      with bifenthrin detected the most frequently and at the highest concentrations.
      In spiked water samples and field samples, the majority of the pyrethroids were
      associated with the suspended sediments.

PMID- 19754148
TI  - Oxidation of fluorinated amorphous carbon (a-CF(x)) films.
AB  - Amorphous fluorinated carbon (a-CF(x)) films have a variety of potential
      technological applications. In most such applications these films are exposed to
      air and undergo partial surface oxidation. X-ray photoemission spectroscopy has
      been used to study the oxidation of fresh a-CF(x) films deposited by magnetron
      sputtering. The oxygen sticking coefficient measured by exposure to low pressures
      (<10(-3) Torr) of oxygen at room temperature is on the order of S approximately
      10(-6), indicating that the surfaces of these films are relatively inert to
      oxidation when compared with most metals. The X-ray photoemission spectra
      indicate that the initial stages of oxygen exposure (<10(7) langmuirs) result in
      the preferential oxidation of the carbon atoms with zero or one fluorine atom,
      perhaps because these carbon atoms are more likely to be found in configurations
      with unsaturated double bonds and radicals than carbon atoms with two or three
      fluorine atoms. Exposure of the a-CF(x) film to atmospheric pressures of air
      (effective exposure of 10(12) langmuirs to O(2)) results in lower levels of
      oxygen uptake than the low pressure exposures (<10(7) langmuirs). It is suggested
      that this is the result of oxidative etching of the most reactive carbon atoms,
      leaving a relatively inert surface. Finally, low pressure exposures to air result
      in the adsorption of both nitrogen and oxygen onto the surface. Some of the
      nitrogen adsorbed on the surface at low pressures is in a reversibly adsorbed
      state in the sense that subsequent exposure to low pressures of O(2) results in
      the displacement of nitrogen by oxygen. Similarly, when an a-CF(x) film oxidized
      in pure O(2) is exposed to low pressures of air, some of the adsorbed oxygen is
      displaced by nitrogen. It is suggested that these forms of nitrogen and oxygen
      are bound to free radical sites in the film.

PMID- 19754150
TI  - Real time, noninvasive imaging and quantitation of the accumulation of ligand
      targeted drugs into receptor-expressing solid tumors.
AB  - Targeted therapies are emerging as a preferred strategy for treatment of cancer
      and other diseases. To evaluate the effect of high affinity receptors on the rate
      and extent of tumor penetration of receptor-targeted drugs, we have characterized
      the kinetics of folate-rhodamine uptake by folate receptor (FR)-expressing tumors
      in live mice. Folate-rhodamine was selected to model receptor-targeted drugs,
      because (i) it has high affinity (K(d) = 10(-9) M) for FR-rich tumors, (ii) its
      uptake can be monitored in vivo by multiphoton microscopy, and (iii) five folate
      targeted drugs of similar size are currently undergoing clinical trials. We
      demonstrate that (1) folate-rhodamine saturates tumor FR in <5 min, <30 min, and
      <100 min following intravenous, paraorbital, and intraperitoneal injection,
      respectively; (2) complete clearance of folate-rhodamine from receptor-negative
      tissues requires > or =50 min, and (3) a "binding site barrier" may retard, but
      does not prevent, penetration of the ligand-targeted drug. We conclude that low
      molecular weight ligand-targeted drugs have appropriate pharmacokinetic
      properties for tumor-selective delivery.

PMID- 19754149
TI  - Replacement of lipopolysaccharide with free lipid A molecules in Escherichia coli
      mutants lacking all core sugars.
AB  - Escherichia coli mutants deficient in 2-keto-3-deoxy-D-manno-octulosonic acid
      (Kdo) biosynthesis are conditionally lethal, but their phenotypes are bypassed by
      certain suppressor mutations or by overexpression of MsbA, the inner membrane
      flippase for core-lipid A. These strains grow on broth with the tetraacylated
      precursor lipid IV(A) replacing lipopolysaccharide [Meredith, T. C., et al.
      (2006) ACS Chem. Biol. 1, 33-42]. Deletion of kdtA, which encodes the Kdo
      transferase, is possible under these conditions. We now show that lipid IV(A)
      reaches the outer surface of the outer membrane in these strains, as judged by
      its accessibility to the lipase PagL. On the assumption that MsbA is optimized to
      transport penta- or hexaacylated lipid A, we overexpressed the lauroyl- or the
      myristoyltransferase of lipid A biosynthesis, encoded by lpxL and lpxM,
      respectively, and demonstrated that kdtA deletion mutants were also viable in
      this setting. Although E. coli LpxL is stimulated by the presence of the Kdo
      disaccharide in its acceptor substrate, LpxL does slowly acylate lipid IV(A).
      Overexpression of LpxL from a plasmid suppressed the lethality of kdtA deletions
      on nutrient broth at 30 or 37 degrees C without the need for MsbA overproduction.
      These strains accumulated penta- and hexaacylated free lipid A containing a
      secondary laurate chain or a laurate and a myristate chain, respectively.
      Deletion of kdtA in strains overexpressing LpxM accumulated pentaacylated lipid A
      with a secondary myristate moiety. None of the strains lacking kdtA grew in the
      presence of bile salts at any temperature or on nutrient broth at 42 degrees C.
      Our findings show that the main function of Kdo is to provide the right
      substrates for the acyltransferases LpxL and LpxM, resulting in the synthesis of
      penta- and hexaacylated lipid A, which is optimal for the MsbA flippase.

PMID- 19754151
TI  - Matrix metalloproteinase 2 inhibition: combined quantum mechanics and molecular
      mechanics studies of the inhibition mechanism of (4
      phenoxyphenylsulfonyl)methylthiirane and its oxirane analogue.
AB  - The inhibition mechanism of matrix metalloproteinase 2 (MMP2) by the selective
      inhibitor (4-phenoxyphenylsulfonyl)methylthiirane (SB-3CT) and its oxirane
      analogue is investigated computationally. The inhibition mechanism involves C-H
      deprotonation with concomitant opening of the three-membered heterocycle. SB-3CT
      was docked into the active site of MMP2, followed by molecular dynamics
      simulation to prepare the complex for combined quantum mechanics and molecular
      mechanics (QM/MM) calculations. QM/MM calculations with B3LYP/6-311+G(d,p) for
      the QM part and the AMBER force field for the MM part were used to examine the
      reaction of these two inhibitors in the active site of MMP2. The calculations
      show that the reaction barrier for transformation of SB-3CT is 1.6 kcal/mol lower
      than its oxirane analogue, and the ring-opening reaction energy of SB-3CT is 8.0
      kcal/mol more exothermic than that of its oxirane analogue. Calculations also
      show that protonation of the ring-opened product by water is thermodynamically
      much more favorable for the alkoxide obtained from the oxirane than for the
      thiolate obtained from the thiirane. A six-step partial charge fitting procedure
      is introduced for the QM/MM calculations to update atomic partial charges of the
      quantum mechanics region and to ensure consistent electrostatic energies for
      reactants, transition states, and products.

PMID- 19754153
TI  - Thermodynamic characterization of the interaction between the C-terminal domain
      of extracellular superoxide dismutase and heparin by isothermal titration
      calorimetry.
AB  - Extracellular superoxide dismutase (ECSOD) interacts with heparin through its C
      terminal domain. In this study we used isothermal titration calorimetry (ITC) to
      get detailed thermodynamic information about the interaction. We have shown that
      the interaction between ECSOD and intestinal mucosal heparin (M(w) 6000-30000 Da)
      is exothermic and driven by enthalpy at physiological salt concentration.
      However, the contribution from entropy is favorable for binding of small isolated
      heparin fragments. By studying different size-defined heparin fragments, we also
      concluded that a hexasaccharide moiety is sufficient for strong binding to ECSOD.
      The binding involves proton transfer from the buffer to the ECSOD-heparin
      complex, and the results indicate that the number of ionic interactions made
      between ECSOD and heparin upon binding varies from three to five for heparin and
      an octasaccharide fragment, respectively. Surprisingly and despite the many
      charges found on both the protein and the polysaccharide, our results indicate
      that the nonionic contribution to the binding is large. From the temperature
      dependence we have calculated the constant pressure heat capacity change
      (DeltaC(p)) of the interaction to -644 J K(-1) mol(-1) and -306 J K(-1) mol(-1)
      for heparin and an octasaccharide, respectively.

PMID- 19754152
TI  - Self-assembled micronanoplexes for improved biolistic delivery of nucleic acids.
AB  - A new method for biolistic delivery of nucleic acids using a combination of
      cationic micro- and nanoparticles is reported. The new method is simpler to
      perform than the conventional calcium/spermidine-based formulations and shows 11
      fold improved nucleic acid binding capacity and dose-dependent performance both
      for in vitro and in vivo applications relative to either the conventional
      preparation or our recently reported direct cationic microparticle method. These
      features may enable higher throughput gene delivery and genetic immunization
      programs and open new venues for the biolistic delivery method.

PMID- 19754154
TI  - An LC-MS-based metabolomics approach for exploring urinary metabolome
      modifications after cocoa consumption.
AB  - Cocoa-phytochemicals have been related to the health-benefits of cocoa
      consumption. Metabolomics has been proposed as a powerful tool to characterize
      both the intake and the effects on the metabolism of dietary components. Human
      urine metabolome modifications after single cocoa intake were explored in a
      randomized, crossed, and controlled trial. After overnight fasting, 10 subjects
      consumed randomly either a single dose of cocoa powder with milk or water, or
      milk without cocoa. Urine samples were collected before the ingestion and at 0-6,
      6-12, and 12-24-h after test-meals consumption. Samples were analyzed by HPLC-q
      ToF, followed by multivariate data analysis. Results revealed an important effect
      on urinary metabolome during the 24 h after cocoa powder intake. These changes
      were not influenced by matrix as no global differences were found between cocoa
      powder consumption with milk or with water. Overall, 27 metabolites related to
      cocoa-phytochemicals, including alkaloid derivatives, polyphenol metabolites
      (both host and microbial metabolites) and processing-derived products such as
      diketopiperazines, were identified as the main contributors to the urinary
      modifications after cocoa powder intake. These results confirm that metabolomics
      will contribute to better characterization of the urinary metabolome in order to
      further explore the metabolism of phytochemicals and its relation with human
      health.

PMID- 19754156
TI  - Cystic fibrosis transmembrane conductance regulator: using differential
      reactivity toward channel-permeant and channel-impermeant thiol-reactive probes
      to test a molecular model for the pore.
AB  - The sixth transmembrane segment (TM6) of the CFTR chloride channel has been
      intensively investigated. The effects of amino acid substitutions and chemical
      modification of engineered cysteines (cysteine scanning) on channel properties
      strongly suggest that TM6 is a key component of the anion-conducting pore, but
      previous cysteine-scanning studies of TM6 have produced conflicting results. Our
      aim was to resolve these conflicts by combining a screening strategy based on
      multiple, thiol-directed probes with molecular modeling of the pore. CFTR
      constructs were screened for reactivity toward both channel-permeant and channel
      impermeant thiol-directed reagents, and patterns of reactivity in TM6 were mapped
      onto two new, molecular models of the CFTR pore: one based on homology modeling
      using Sav1866 as the template and a second derived from the first by molecular
      dynamics simulation. Comparison of the pattern of cysteine reactivity with model
      predictions suggests that nonreactive sites are those where the TM6 side chains
      are occluded by other TMs. Reactive sites, in contrast, are generally situated
      such that the respective amino acid side chains either project into the predicted
      pore or lie within a predicted extracellular loop. Sites where engineered
      cysteines react with both channel-permeant and channel-impermeant probes occupy
      the outermost extent of TM6 or the predicted TM5-6 loop. Sites where cysteine
      reactivity is limited to channel-permeant probes occupy more cytoplasmic
      locations. The results provide an initial validation of two, new molecular models
      for CFTR and suggest that molecular dynamics simulation will be a useful tool for
      unraveling the structural basis of anion conduction by CFTR.

PMID- 19754155
TI  - Structural insights into glucan phosphatase dynamics using amide hydrogen
      deuterium exchange mass spectrometry.
AB  - Laforin and starch excess 4 (SEX4) are founding members of a class of
      phosphatases that dephosphorylate phosphoglucans. Each protein contains a
      carbohydrate binding module (CBM) and a dual-specificity phosphatase (DSP)
      domain. The gene encoding laforin is mutated in a fatal neurodegenerative disease
      called Lafora disease (LD). In the absence of laforin function, insoluble glucans
      that are hyperphosphorylated and exhibit sparse branching accumulate. It is
      hypothesized that these accumulations trigger the neurodegeneration and premature
      death of LD patients. We recently demonstrated that laforin removes phosphate
      from phosphoglucans and hypothesized that this function inhibits insoluble glucan
      accumulation. Loss of SEX4 function in plants yields a similar cellular
      phenotype; an excess amount of insoluble, hyperphosphorylated glucans accumulates
      in cells. While multiple groups have shown that these phosphatases
      dephosphorylate phosphoglucans, there is no structure of a glucan phosphatase and
      little is known about the mechanism whereby they perform this action. We utilized
      hydrogen-deuterium exchange mass spectrometry (DXMS) and structural modeling to
      probe the conformational and structural dynamics of the glucan phosphatase SEX4.
      We found that the enzyme does not undergo a global conformational change upon
      glucan binding but instead undergoes minimal rearrangement upon binding. The CBM
      has improved protection from deuteration when bound to glucans, confirming its
      role in glucan binding. More interestingly, we identified structural components
      of the DSP that also have improved protection from deuteration upon glucan
      addition. To determine the position of these regions, we generated a homology
      model of the SEX4 DSP. The homology model shows that all of these regions are
      adjacent to the DSP active site. Therefore, our results suggest that these
      regions of the DSP participate in the presentation of the phosphoglucan to the
      active site and provide the first structural analysis and mode of action of this
      unique class of phosphatases.

PMID- 19754157
TI  - Steric and electrostatic complementarity in the assembly of two-dimensional virus
      arrays.
AB  - A highly ordered assembly of biological molecules provides a powerful means to
      study the organizational principles of objects at the nanoscale. Two-dimensional
      cowpea mosaic virus arrays were assembled in an ordered manner on mica using
      osmotic depletion effects and a drop-and-dry method. The packing of the virus
      array was controlled systematically from rhombic packing to hexagonal packing by
      modulating the concentrations of poly(ethylene glycol) surfactant in the virus
      solutions. The orientation and packing symmetry of the virus arrays were found to
      be tuned by the concentrations of surfactants in the sample solutions. A
      phenomenological model for the present system is proposed to explain the assembly
      array morphology under the influence of the surfactant. Steric and electrostatic
      complementarity of neighboring virus capsids is found to be the key factors in
      controlling the symmetry of packing.

PMID- 19754158
TI  - Intrinsic dynamics in ECFP and Cerulean control fluorescence quantum yield.
AB  - Enhanced cyan fluorescent protein (ECFP) and its variant Cerulean are genetically
      encoded fluorophores widely used as donors in FRET-based cell imaging
      experiments. First, we have confirmed through denaturation experiments that the
      double-peak spectroscopic signature of these fluorescent proteins originates from
      the indole ring of the chromophore. Then, to explain the improvement in the
      fluorescence properties of Cerulean compared to those of ECFP, we have determined
      the high-resolution crystal structures of these two proteins at physiological pH
      and performed molecular dynamics simulations. In both proteins, the N-terminal
      half of the seventh strand exhibits two conformations. These conformations both
      have a complex set of van der Waals interactions with the chromophore and, as our
      simulations suggest, they interconvert on a nanosecond time scale. The Y145A and
      H148D mutations in Cerulean stabilize these interactions and allow the
      chromophore to be more planar, better packed, and less prone to collisional
      quenching, albeit only intermittently. As a consequence, the probability of
      nonradiative decay is significantly decreased. Our results highlight the
      considerable dynamical flexibility that exists in the vicinity of the tryptophan
      based chromophore of these engineered fluorescent proteins and provide insights
      that should allow the design of mutants with enhanced optical properties.

PMID- 19754159
TI  - [(3)H]chlorpromazine photolabeling of the torpedo nicotinic acetylcholine
      receptor identifies two state-dependent binding sites in the ion channel.
AB  - Chlorpromazine (CPZ), a potent nicotinic acetylcholine receptor (nAChR)
      noncompetitive antagonist, binds with higher affinity in the ion channel in the
      desensitized state than in the closed channel state and with low affinity to
      additional sites in nAChR-rich membranes. For nAChR equilibrated with agonist, we
      confirm previous reports that [(3)H]CPZ occupies a site near the cytoplasmic end
      of the M2 ion channel domain, photolabeling positions M2-2, M2-6, and/or M2-9 in
      each subunit. We find that [(3)H]CPZ also binds at the extracellular end of the
      channel, photolabeling amino acids at positions M2-16 (alpha,gamma), M2-17
      (alpha,beta,delta), and M2-20 (alpha,beta,delta). The photolabeling at the
      cytoplasmic end of the channel is fully inhibitable by phencyclidine or
      proadifen, whereas neither drug inhibits [(3)H]CPZ photolabeling at the
      extracellular end, establishing that positively charged drugs can bind
      simultaneously at the cytoplasmic and extracellular ends of the ion channel.
      [(3)H]CPZ photolabeling is not detected in the transmembrane domain outside the
      ion channel, but it photolabels alphaMet-386 and alphaSer-393 in the cytoplasmic
      alphaMA helix. In the nAChR equilibrated with alpha-bungarotoxin to stabilize the
      nAChR in a closed state, [(3)H]CPZ photolabels amino acids at M2-5 (alpha), M2-6
      (alpha,beta,delta), and M2-9 (beta,delta), with no labeling at M2-2. These
      results provide novel information about the modes of drug binding within the
      nAChR ion channel and indicate that within the nAChR transmembrane domain, the
      binding of cationic aromatic amine antagonists can be restricted to the ion
      channel domain, in contrast to the uncharged, allosteric potentiators and
      inhibitors that also bind within the delta subunit helix bundle and at subunit
      interfaces.

PMID- 19754160
TI  - Copper binding to beta-2-microglobulin and its pre-amyloid oligomers.
AB  - Beta-2-microglobulin (beta2m) deposits as amyloid fibrils in the musculoskeletal
      system of patients undergoing long-term dialysis treatment as a result of kidney
      failure. Previous work has shown that Cu(II) binding causes beta2m to organize
      into nativelike dimers and tetramers that precede amyloid formation. Cu(II) is
      then released from higher-order oligomers before mature Cu(II)-free amyloid
      fibrils are formed. While some of the Cu(II)-induced structural changes that
      enable beta2m self-assembly are starting to be revealed, the details of how the
      Cu(II) binding site evolves from the monomer to the dimers and tetramers are not
      known. Here, we report results from three mass spectrometry (MS)-based methods
      that provide insight into the changing Cu-beta2m interactions. We find that
      monomeric beta2m binds Cu(II) via the N-terminal amine, the amide of Gln2, His31,
      and Asp59. In the dimer and tetramer, Asp59 is no longer bound to Cu(II), but the
      other residues still comprise a well-defined albeit weaker binding site that is
      better able to release Cu(II). Consistent with this is the observation that a
      fraction of the tetrameric species no longer binds Cu(II) at this weakened
      binding site, which agrees with a previous report that suggested the tetramer as
      the first Cu(II)-free oligomer. Our results also provide some insight into
      structural changes caused by Cu(II) binding that facilitate oligomer formation.
      Specifically, binding by Asp59 in the monomer requires significant movement of
      this residue, and we propose that this repositioning is important for
      establishing a pair of dimer-stabilizing salt bridges between this residue and
      Lys19. We also find evidence that Cu(II) binding in the N-terminal region of the
      monomer repels Arg3, which likely allows this residue to form a pair of dimer
      stabilizing salt bridges with Glu16. Overall, our measurements suggest that the
      previously proposed conformational switch caused by Cu(II) binding includes not
      only a cis-trans isomerization at Pro32 but also the repositioning of residues
      that are critical for the formation of new electrostatic interactions.

PMID- 19754161
TI  - Analytical error reduction using single point calibration for accurate and
      precise metabolomic phenotyping.
AB  - Analytical errors caused by suboptimal performance of the chosen platform for a
      number of metabolites and instrumental drift are a major issue in large-scale
      metabolomics studies. Especially for MS-based methods, which are gaining common
      ground within metabolomics, it is difficult to control the analytical data
      quality without the availability of suitable labeled internal standards and
      calibration standards even within one laboratory. In this paper, we suggest a
      workflow for significant reduction of the analytical error using pooled
      calibration samples and multiple internal standard strategy. Between and within
      batch calibration techniques are applied and the analytical error is reduced
      significantly (increase of 25% of peaks with RSD lower than 20%) and does not
      hamper or interfere with statistical analysis of the final data.

PMID- 19754162
TI  - Proteolysis: a biological process adapted in drug delivery, therapy, and imaging.
AB  - In many diseases, protease expressions are found deregulated when compared with
      them at the healthy states. The unique ability to hydrolyze protein amide bonds
      has made those deregulated proteases attractive biological triggers in drug
      development. Proteolysis has been widely applied in pro-drug design to achieve
      favorable pharmacokinetics. Controlled drug delivery systems are also reported by
      incorporating protease-sensitive motifs onto bio-, inorganic-, or organic-
      materials. In addition, protease responsive molecular probes are developed for in
      vitro bioanalysis and in vivo diagnostic imaging. This review focuses on various
      proteolysis-dependent approaches to drug delivery, therapy, and imaging.
      References are selected to illustrate the concepts and demonstrate the potentials
      of these enzyme-responsive strategies.

PMID- 19754163
TI  - Development of a glucose biosensor for rapid assessment of strawberry quality:
      relationship between biosensor response and fruit composition.
AB  - Sugars are intimately related to the taste of strawberry fruit and therefore to
      quality. A disposable prototype glucose biosensor was constructed using glucose
      oxidase (GOx) immobilized onto Meldolas Blue mediated screen printed electrodes,
      to determine glucose content in diluted strawberry juices. Several experimental
      variables that affect biosensor performance, such as applied potential, GOx
      loading, and pH of the buffer/electrolyte solution were optimized by means of a
      2(3) central composite design. Optimum applied potential, pH, and enzyme loading
      were +300 mV (versus Ag/AgCl), 7.2, and 20 U, respectively. Although the linear
      range (0-10 mM) was not significantly affected by the optimization process, the
      signal given by the biosensor was increased by as much as 3-fold as compared to
      preliminary experiments, and the reproducibility of the measurements was
      improved. Unlike total soluble solids (TSS), and as hypothesized, the constructed
      GOx biosensor was able to discriminate and rank eight different strawberry
      cultivars on the basis of their glucose content when compared to known
      concentrations measured by standard HPLC. A detailed study of the possible
      interferences (viz. total phenolics, antioxidant capacity, and organic acids)
      found in strawberry samples that could affect biosensor performance was also
      performed to further understand the relationship between biosensor response and
      sample composition. Under the imposed experimental conditions the constructed
      biosensor acted interference-free.

PMID- 19754164
TI  - In situ determination of lignin phenolics and wood solubility in imidazolium
      chlorides using (31)P NMR.
AB  - Corn stover, Norway spruce, and Eucalyptus grandis were pulverized to different
      degrees. These samples were subjected to quantitative analyses, upon the basis of
      predissolution into the imidazolium chloride-based ionic liquids [amim]Cl and
      [bnmim]Cl followed by labeling of hydroxyl groups as phosphite esters and
      quantitative (31)P NMR analysis. Analysis of different pulverization degrees
      provided semiempirical data to chart the solubility of Norway spruce in these
      ionic liquids. Further method refinment afforded an optimized method of analysis
      of the lignin phenolic functionalities, without prior isolation of the lignin
      from the fiber. The lignin in these samples was further enriched using cellulase
      and acidolysis treatments, allowing for comparison with the fibrous samples.
      Analysis of all samples charts the polymerized-monomer availability for each
      stage of the treatment. Conditions required for adequate signal-to-noise ratios
      in the (31)P NMR analysis were established with a notable improvement observed
      upon the lignin enrichment steps.

PMID- 19754165
TI  - Determination of the country of origin of farm-raised shrimp (family penaeide)
      using trace metal profiling and multivariate statistics.
AB  - The role of Customs and Border Protection on shrimp importations into the United
      States is discussed. The focus of this work is to present evidence that the
      comparison of trace metal data from an imported shrimp sample to an authentic
      reference database using multivariate statistics produces an accurate geographic
      location of the sample. The authentic reference database includes data from more
      than 100 sampling sites spread over eight countries along with the accuracy of
      each site relative to its known geographic origin. Potential sources of
      bioaccumulation are briefly discussed; however, it is beyond the scope of this
      work to provide scientific verification of the mechanism for trace metal uptake.
      Three examples of imported shrimp are provided for demonstrating the exact
      procedure for determining their true countries of origin.

PMID- 19754166
TI  - Rapid measurement of 3-alkyl-2-methoxypyrazine content of winegrapes to predict
      levels in resultant wines.
AB  - We describe an optimized protocol for analysis of the herbaceous smelling 3-alkyl
      2-methoxypyrazines (MPs) in whole berries that predicts MPs in resultant red
      wines. Berries are homogenized by bead-milling with a deuterated standard prior
      to headspace solid phase microextraction (HS-SPME) and quantification by two
      dimensional gas chromatography time-of-flight-mass-spectrometry (GCxGC-TOF-MS).
      In the case of 3-isopropyl-2-methoxypyrazine (IPMP), GCxGC-TOF-MS successfully
      resolved interferences that coeluted with the analyte in the first dimension. HS
      SPME parameters (pH, queue time, incubation time, extraction time, extraction
      temperature) were optimized by a statistical experimental design. Good method
      accuracy was observed (consistent ratio of unlabeled analyte to labeled standard)
      at 10 min extraction times when 80 degrees C extraction temperatures were
      employed, although increasing sensitivity was observed for longer extraction
      times (up to 140 min). Standard addition of 3-isobutyl-2-methoxypyrazine (IBMP)
      and IPMP into preveraison and harvest ripe berry matrices showed good linearity
      (r(2) >0.99 in all cases), with limits of detection ranging from 0.6 to 1.8 pg/g.
      The protocol was validated by comparing IBMP in 16 lots of Cabernet Franc berries
      (range = undetectable to 18.4 pg/g) to the resulting wines (range = undetectable
      to 14.5 pg/g). Berry and wine MP content were strongly correlated, (r(2) = 0.97,
      p < 0.0001). Following correction for CO(2) loss, the observed concentration of
      IBMP in wines was 67 +/- 13% of the IBMP concentration observed in berries.

PMID- 19754167
TI  - The Monascus metabolite monacolin K reduces tumor progression and metastasis of
      Lewis lung carcinoma cells.
AB  - Monascus -fermented red mold rice extract (RMRE) offers valuable therapeutic
      benefits and has been extensively used for centuries in East Asia. Monascus
      secondary polyketide metabolites, including monacolin K (MK) and ankaflavin (AK),
      have been reported to have antitumor-initiating effects on cancer progression.
      This paper reports that the oral administration of RMRE dramatically inhibited
      the metastatic ability of murine Lewis lung carcinoma (LLC) cells in syngeneic
      C57BL/6 mice caused by the decline of serum vascular endothelial growth factor
      (VEGF) levels compared with untreated metastatic groups. MK is a key
      antimetastatic and antiangiogenesis compound in RMRE, as shown by down-regulation
      of VEGF-stimulated invasive activity in LLC cells by Matrigel-coating transwell
      and tube-forming assays and reverse transcription-Polymerase Chain Reaction (RT
      PCR). Therefore, application of RMRE may serve as a nontoxic natural
      chemopreventive or antineoplastic agent in the development of cancer adjuvant
      chemotherapy.

PMID- 19754168
TI  - Preventive effect of crocin in inflamed animals and in LPS-challenged RAW 264.7
      cells.
AB  - Gardenia jasminoides Ellis and Crocus sativus L. are both traditional Chinese
      medicines that have significant biologic activities on inflammatory processes.
      But the active ingredients remain unclear. Crocin, a representative of carotenoid
      compounds, has now drawn considerable attention not only because it is a natural
      food colorant but also because it has great potential in medicine. But until now,
      the systematic anti-inflammatory effect of crocin has not been well established.
      In the present study, experiments were carried out to evaluate the anti
      inflammatory effects of crocin in vitro and in vivo. In vitro, cyclooxygenase
      (COX) inhibition assays showed that crocin exhibits a dual inhibitory activity
      against the COX-1 and COX-2 enzymes. Anti-inflammatory activity in vivo was
      evaluated using two animal edema model tests. Pretreatment with crocin (p.o.)
      dose-dependently inhibited the xylene-induced ear edema in mice and carrageenan
      induced paw edema in rats. In gastric lesion tests, crocin was gastric-sparing in
      that it elicited markedly fewer stomach lesions as compared to the number of
      stomach lesions caused by indomethacin in rats. In further studies, crocin was
      found to significantly inhibit the productions of prostaglandin E(2) (PGE(2)) in
      lipopolysaccharide (LPS)-challenged RAW 264.7, which is parallel to its
      prevention of the nuclear translocation of the NF-kappaB p50 and p65 subunits.
      These data indicate that crocin exhibits obvious anti-inflammatory effects and
      may be one of the active ingredients in Gardenia jasminoides Ellis or Crocus
      sativus L. that can modulate inflammatory processes.

PMID- 19754169
TI  - Comparison of methods for extracting kafirin proteins from sorghum distillers
      dried grains with solubles.
AB  - Use of coproducts generated during fermentation is important to the overall
      economics of biofuel production. The main coproduct from grain-based ethanol
      production is distillers dried grains with solubles (DDGS). High in protein, DDGS
      is a potential source of protein for many bioindustrial applications such as
      adhesives and resins. The objective of this research was to characterize the
      composition as well as chemical and physical properties of kafirin proteins from
      sorghum DDGS with various extraction methods including use of acetic acid, HCl
      ethanol and NaOH-ethanol under reducing conditions. Extraction conditions
      affected purity and thermal properties of the extracted kafirin proteins.
      Extraction yields of 44.2, 24.2, and 56.8% were achieved by using acetic acid,
      HCl-ethanol and NaOH-ethanol, respectively. Acetic acid and NaOH-ethanol produced
      protein with higher purity than kafirins extracted with the HCl-ethanol protocol.
      The acetic acid extraction protocol produced protein with the highest purity,
      98.9%. Several techniques were used to evaluate structural, molecular and thermal
      properties of kairin extracts. FTIR showed alpha-helix dominated in all three
      samples, with only a small portion of beta-sheet present. Electrophoresis results
      showed alpha(1), alpha(2) band and beta kafirins were present in all three
      extracts. Glass transition peaks of the extracts were shown by DSC to be
      approximately 230 degrees C. Kafirin degraded at 270-290 degrees C. Size
      exclusion chromatography revealed that the acetic acid and HCl-ethanol based
      extraction methods tended to extract more high molecular weight protein than the
      NaOH-ethanol based method. Reversed phase high-performance liquid chromatography
      showed that the gamma kafirins were found only in extracts from the NaOH-ethanol
      extraction method.

PMID- 19754170
TI  - Determination of the bovine food allergen casein in white wines by quantitative
      indirect ELISA, SDS-PAGE, Western blot and immunostaining.
AB  - This study describes the characterization of allergic bovine casein and caseinate
      fining agents by SDS-PAGE analysis and the development of a quantitative indirect
      ELISA for the detection of these substances in wines. The ELISA was applied to
      various experimental wines that were treated with different caseinate dosages and
      went through different processing steps and to a panel of commercial wines.
      Positive results were assured by SDS-PAGE, Western blot, and immunostaining.
      Comprehensive literature research was done to evaluate the demanded sensitivity
      of the ELISA. The results showed that alpha- and beta-caseins remain in some
      wines and are detectable. Estimated amounts were in the range or below an
      estimated no-observed adverse effect level (NOAEL) of 0.9 mg/L, but it was
      concluded that there is still an uncertainty about this NOAEL. Additional applied
      processing, referring to bentonite treatment and successive filtration, was
      determined to contribute to a significant decrease of casein residues in wines.

PMID- 19754171
TI  - Efficacy of 1,3-dichloropropene gelatin capsule formulation for the control of
      soilborne pests.
AB  - The gelatin capsule (gel cap) formulation of 1,3-dichloropropene (1,3-D) is a new
      concept to reduce the environmental release, transport, and hazard potential of
      the use of 1,3-D to control soilborne diseases and nematodes. The objective of
      this study is to evaluate the biological efficacy of the 1,3-D gel cap
      formulation under laboratory and greenhouse trial conditions. Greenhouse
      experiments were carried out in suburbs of Beijing and Hebei Province of China in
      2007 and 2008, focused mainly on tomato and Bellis perennis L. (daisy) crops.
      Results showed that 1,3-D gel cap application at a rate of 16.8 g of active
      ingredient m(-2) was as effective as 1,3-D liquid injection treatment. Crop
      yields in plots treated with 1,3-D gel cap and 1,3-D liquid were significantly
      higher than those in untreated control. The present study confirms that the 1,3-D
      gel cap formulation is a promising new formulation with good field efficacy.

PMID- 19754172
TI  - Color and polyphenolic stability in extracts produced from muscadine grape (Vitis
      rotundifolia) pomace.
AB  - The muscadine grape ( Vitis rotundifolia ) industry of the southern United States
      is largely devoid of value-added processes that capture the phytochemical content
      of wine and juice byproducts. Methods to recover and stabilize polyphenolics from
      muscadine grape pomace following juice manufacture were evaluated in laboratory
      scale and pilot-scale trials. In laboratory-scale trials using osmotic
      equilibration, water-based extracts from juice pomace initially extracted 31-42%
      of total polyphenolics, 26-32% of total ellagic acid, and 36-62% of total
      anthocyanins. When adsorbed onto Amberlite XAD-4 resin to concentrate
      polyphenolics, these extracts lost 10.5% of their total ellagic acid from
      inefficient adsorption to the solid phase support. Subsequent pilot-scale trials
      were evaluated using hot water extracts from grape juice pomace followed by
      aerobic yeast fermentation to remove sugars and comparison to reversed phase
      C(18) and Amberlite XAD-4. Extracts were also concentrated using spray-drying and
      vacuum evaporation. Fermentation had a minor impact on the retention of most
      polyphenolic compounds evaluated, yet resulted in a 16.3% decrease in antioxidant
      capacity. Spray-drying resulted in a 30.3% loss in total anthocyanins, a 21.5%
      loss in total phenolics, and a 23.3% decrease in antioxidant activity, whereas
      vacuum evaporation had no deleterious impact on these parameters. The physiology
      of the muscadine grape and its unique phytochemical composition has limited
      utilization of pomace from wine and juice manufacture. However, these studies
      demonstrated the potential to extract and concentrate polyphenolic-rich extracts
      for use in value-added applications.

PMID- 19754173
TI  - Extensive dry ball milling of wheat and rye bran leads to in situ production of
      arabinoxylan oligosaccharides through nanoscale fragmentation.
AB  - This study investigated the potential of ball milling as a dry process for in
      situ production of arabinoxylan oligosaccharides (AXOS) in arabinoxylan (AX)-rich
      wheat and rye bran. An extensive lab-scale ball mill treatment (120 h, 50% jar
      volume capacity) increased the wheat bran water-extractable arabinoxylan (WE-AX)
      level from 4% (untreated bran) to 61% of the wheat bran AX. Extractable AX
      fragments had an arabinose/xylose ratio (A/X ratio) of 0.72 and a molecular mass
      (MM) of 15 kDa. Ball milling of rye bran gave rise to similar results, with the
      A/X ratio of the extractable AX being considerably lower (0.51). Optimization of
      the ball mill treatment by varying the degree of filling of the milling jar
      permitted us to obtain equally high WE-AX levels (>70%) in wheat and rye bran
      within a 24 h ball-milling period. Ball milling at optimal conditions (24 h, 16%
      jar volume capacity) yielded wheat bran AXOS, with an A/X ratio of 0.65 and a MM
      of 6 kDa. Ball milling (24 h, 50% jar volume capacity) of pericarp-enriched wheat
      bran increased the WE-AX level from 1% (untreated pericarp) to 63%. The
      extractable material had a high A/X ratio (0.97) and a low MM (5 kDa).
      Fluorescence microscopy revealed that the extensive ball mill treatment led to
      the almost complete disappearance of discernible tissue structures in the ball
      milled material, indicating bran particle size reductions down to the nanoscale
      level. It further visualized the aggregation of the treated material. These
      results show that AXOS can be produced in situ from wheat or rye bran in a single
      stage dry milling process, rendering a wet extraction step redundant. The higher
      A/X ratio of the obtained AXOS than of enzymically produced wheat bran-derived
      AXOS offers perspectives for the production of a wide range of AXOS structures.
      Moreover, ball milling makes upgrading of the low-value pericarp layer feasible.

PMID- 19754174
TI  - Fate of key odorants in Sauternes wines through aging.
AB  - Recent work has revealed the importance of polyfunctional thiols in young
      Sauternes wines, but very little is yet known about the fate of such compounds
      during aging in the bottle. In this study, two Sauternes wines were investigated
      by gas chromatography-olfactometry (GC-O) aroma extract dilution analysis (AEDA),
      gas chromatography-mass spectrometry (GC-MS), and gas chromatography-pulsed flame
      photometric detector (GC-PFPD) after XAD 2 and thiol-specific extractions. Most
      polyfunctional thiols (3-sulfanylpropyl acetate, 2-sulfanylethyl acetate, 3
      methyl-3-sulfanylbutanal, etc.) proved to be completely degraded after 2 years of
      bottle aging in a cellar. Only 3-sulfanylhexan-1-ol was still found in aged
      samples at concentrations above its threshold value. Most other key odorants
      found in the young noble rot wine were still detected 5-6 years after harvest:
      varietal aroma (alpha-terpineol), sotolon, fermentation alcohols (3-methylbutan-1
      ol and 2-phenylethanol) and esters (ethyl butyrate, isobutyrate, hexanoate, and
      isovalerate), and oak maturation-related compounds (guaiacol, vanillin, eugenol,
      beta-damascenone, trans-non-2-enal, beta-methyl-gamma-octalactone, gamma
      nonalactone, and furaneol), as well as three newly identified aromas exhibiting
      interesting cake, honey-like, and dried apricot odors: homofuraneol, theaspirane,
      and gamma-decalactone. Interestingly, abhexon, never mentioned in sweet wines
      before, was found to be synthesized during bottle aging. An optimized extraction
      method allowed us to quantify this honey/spicy compound at levels close to its
      threshold value (up to 7 microg/L after 5-6 years), thus suggesting a key role of
      this strong odorant in old Sauternes wines.

PMID- 19754175
TI  - Release of the cell-envelope-associated proteinase of Lactobacillus delbrueckii
      subspecies lactis CRL 581 is dependent upon pH and temperature.
AB  - The cell-envelope-associated proteinase of Lactobacillus delbrueckii subsp.
      lactis CRL 581 (PrtL) has an essential role in bacterial growth and contributes
      to the development of the organoleptic properties of hard cheeses and to the
      release of bioactive health-beneficial peptides from milk proteins. In this
      study, the effect of environmental pH on PrtL production by L. delbrueckii subsp.
      lactis CRL 581 in a chemically defined medium and the influence of pH,
      temperature, and Ca(2+) ions on PrtL activity, stability, and release from the
      cell envelope were analyzed. The maximum PrtL activity levels were observed in
      the middle of the exponential growth phase, with the values at constant pH of 5.5
      and 6.0 being higher than those observed at pH 4.5 and 5.0. At pH 4.5, PrtL
      remained mainly associated with the cell envelope, whereas at pH values of 5.5 or
      higher, approximately 40% of PrtL was found in the medium. In addition, the PrtL
      activity was stable for 24 h at 4 and 25 degrees C, and its release at 4, 25, and
      40 degrees C was time-dependent. PrtL activity, stability, and release were
      independent of the presence of Ca(2+) ions in the medium. These results indicated
      that, at pH and temperature conditions found during the manufacture of hard
      cheeses, PrtL would remain active either bound to the cell or released in the
      supernatant contributing to the organoleptic characteristics and beneficial
      health effects of the fermented milk products.

PMID- 19754176
TI  - Fucoidan induces apoptosis through activation of caspase-8 on human breast cancer
      MCF-7 cells.
AB  - Fucoidan is an active component of seaweed that has been shown to inhibit
      proliferation and induce apoptotic cell death in several tumor cells. However,
      the detailed mechanisms underlying this process have not yet been elucidated. In
      the present report, we investigated the effect of fucoidan on the induction of
      apoptosis in human breast cancer MCF-7 cells. Our data demonstrated that fucoidan
      reduced the viable cell number of MCF-7 cells in a dose- and time-dependent
      manner. In contrast, fucoidan did not affect the viable cell number of normal
      human mammary epithelial cells. Results from the apoptosis assay demonstrated
      that fucoidan induced internucleosomal DNA fragmentation, chromatin condensation,
      activation of caspase-7, -8, and -9, and cleavage of poly(ADP ribose) polymerase.
      Furthermore, expression of Bid was decreased, whereas truncated Bid was increased
      by fucoidan treatment. There was also a decline in cytosolic Bax and a striking
      increase of cytosolic cytochrome c. Caspase-8-specific inhibitor, z-ITED-fmk,
      canceled the cytotoxicity of fucoidan, activation of caspase-7, -8, and -9, and a
      series of changes in Bax, Bid, and cytochrome c. However, caspase-9-specific
      inhibitor exerted a moderate inhibitory effect on the cytotoxicity of fucoidan.
      These data indicated that fucoidan could induce apoptotic cell death through a
      caspase-8-dependent pathway in MCF-7 cells.

PMID- 19754177
TI  - Antithrombotic and fibrinolytic activities of methanolic extract of aged sorghum
      vinegar.
AB  - Antithrombotic activities, namely, in vitro platelet aggregation and in vivo
      pulmonary thrombosis, of the methanolic extract of aged vinegar were evaluated.
      The ability of the extract to inhibit platelet aggregation induced by adenosine
      diphosphate (ADP) and thrombin was concentration-dependent. IC(50) values for the
      inhibition of platelet aggregation induced by ADP and thrombin were 1.7 +/- 0.3
      and 8.9 +/- 1.9 mg/mL, respectively. When administered orally at >100 mg/kg of
      body weight, the extract protected the rats against thrombotic death induced by
      collagen and epinephrine. Furthermore, the low molecular weight fraction of the
      extract showed strong fibrinolytic activity and altered coagulation parameters
      such as activated partial thromboplastin time (APTT), prothrombin time (PT), and
      throbin time (TT) in rat platelet. These results suggested that the
      antithrombotic ability of the vinegar extract corresponded to both antiplatelet
      and anticoagulation activities.

PMID- 19754178
TI  - RNA-mediated electron transfer: double exponential distance dependence.
AB  - We describe the long-range excess electron transfer through RNA duplexes
      consisting of a pyrene electron donor and a nitrobenzene electron acceptor that
      shows double exponential distance dependence.

PMID- 19754179
TI  - "Too small, too big, and just right"--optical sensing of molecular conformations
      in self-assembled capsules.
AB  - Irradiation of dimethylbenzil within a cylindrical capsule gives bright green
      phosphorescence, while irradiation of benzil and dimethoxybenzil in the same
      capsule results in high energy blue fluorescence. This difference is likely due
      to the geometric restrictions imposed by the capsule's space on its excited
      guests, forcing a trans-planar conformation in some cases and cis-skewed in
      others.

PMID- 19754180
TI  - Metal-molecule-metal junctions via PFPE assisted nanotransfer printing (nTP) onto
      self-assembled monolayers.
AB  - We report a simple method to form metal-molecule-metal junctions (MMMs) via
      nanotransfer printing with low surface energy perfluoropolyether (PFPE) based
      stamps. Transfer printing is demonstrated onto thermally deposited metal thin
      film electrodes where the root-mean-squared roughness of these films is
      controlled by the deposition process and varies by 40% or more. Transfer of Au
      and Co thin films is reported onto Au/SAM and Co/SAM electrodes in well-ordered,
      200 nm MMM arrays; furthermore, nickel nanotransfer printing is shown for the
      first time in the construction of 200 nm arrays of Ni/SAM/Ni junctions. The
      nanotransfer printing we report is reproducible in high fidelity which is
      required in the application of practical molecular electronic devices. Current
      voltage characteristics are presented.

PMID- 19754181
TI  - Construction of highly reactive probes for abasic site detection by introduction
      of an aromatic and a guanidine residue into an aminooxy group.
AB  - Abasic sites (AP sites) arise from hydrolysis of glycosidic bonds of DNA that is
      damaged by various external and internal processes; unrepaired AP sites give rise
      to genetic mutations. We have constructed highly reactive AP-site-detecting
      probes by introducing a hydrophobic and a hydrophilic residue in an aminooxy
      group. Synthesized probes containing either a naphthalene or a guanidine residue
      conjugate effectively with AP sites. In particular, a probe containing both
      functional groups shows the highest reaction rate, indicating that the
      hydrophobic and hydrophilic interactions act cooperatively in reaction with AP
      sites. The guanidine residue also contributes to the solubility of the molecules
      in aqueous media. The biotinylated probes provide much more sensitive detection
      of AP sites in genomic DNA than the conventional aldehyde-reactive probe.

PMID- 19754182
TI  - Polyelectrolyte synthesis and in situ complex formation in ionic liquids.
AB  - For the first time, polyelectrolyte complex (PEC) capsules were prepared from a
      water insoluble polyanion, namely cellulose sulfates (CSs) with a degree of
      substitution (DS) below 0.2 in ionic liquids (IL). Capsules prepared via
      interaction with the polycation poly(dimethyldiallyammonium chloride) were free
      of residual IL and possessed an outer shell and a hollow inner core that made
      them ideal containers for enzyme mediated reactions. Due to the reestablished
      hydrogen bond system of the low substituted CS, the capsules showed increased
      stability, compared to the products obtained by application of the common aqueous
      preparation. Encapsulation of glucose oxidase demonstrated that the steps of CS
      preparation, PEC capsule formation, and encapsulation could be combined in a
      single pot, with the elimination of time and cost consuming isolation and
      purification steps.

PMID- 19754183
TI  - Effect of contrast agent charge on visualization of articular cartilage using
      computed tomography: exploiting electrostatic interactions for improved
      sensitivity.
AB  - The synthesis and evaluation of a new class of cationic iodinated contrast agents
      for the imaging of cartilage using computed tomography (CT) are described. In
      direct comparisons with anionic contrast agents, the cationic contrast agents
      afforded higher equilibrium concentrations in the articular cartilage of ex vivo
      rabbit femurs and thus greater imaging sensitivity. Variations in CT intensity
      across the sample reflected the inhomogeneous distribution of glycosaminoglycans
      in the tissue as confirmed by histological analysis. We anticipate that this work
      represents the first step in the development of sensitive, nondestructive CT
      based methods to characterize the biochemical properties of cartilage using
      cationic contrast agents.

PMID- 19754184
TI  - Monodisperse co-oligomer approach toward nanostructured films with alternating
      donor-acceptor lamellae.
AB  - A series of donor-acceptor (D-A) co-oligomers with oligo(fluorene-alt
      bithiophene) and perylene diimide as donor and acceptor segments, respectively,
      have been designed and synthesized. They can self-assembly into alternating D-A
      lamellar nanostructured films with the periods depending on the molecular length.
      These films have been successfully used in fabrication of high-performance single
      molecular solar cells with power conversion efficiency up to 1.50%.

PMID- 19754185
TI  - Total synthesis of alkaloid (+/-)-G. B. 13 using a Rh(I)-catalyzed ketone
      hydroarylation and late-stage pyridine reduction.
AB  - Total synthesis of the Galbulimima alkaloid G. B. 13 was achieved utilizing a
      functionalized pyridine moiety as a piperidine surrogate. Key to the success of
      the synthesis was the development of an unprecedented rhodium-catalyzed 1,2
      addition of an arylboronic ester into an unactivated ketone.

PMID- 19754186
TI  - Hydration of alkaline earth metal dications: effects of metal ion size determined
      using infrared action spectroscopy.
AB  - Infrared laser action spectroscopy is used to characterize divalent Mg, Ca, and
      Ba ions solvated by discrete numbers of water molecules in the gas phase. The
      spectra of the hexahydrated ions are very similar and indicate that all six water
      molecules directly solvate the metal ion. The spectra of the heptahydrated ions
      indicate the presence of populations of structures that have a water molecule in
      the outer shell for all ions and an average coordination number (CN) for Ba that
      is higher than that for Ca or Mg. Comparisons between CN values obtained from M06
      density functional and local MP2 theory indicate that the B3LYP density
      functional favors smaller CN values. The spectra of clusters containing at least
      12 water molecules indicate that the relative abundance of single-acceptor water
      molecules for a given cluster size decreases with increasing metal ion size,
      indicating that tighter water binding to smaller metal ions disrupts the hydrogen
      bond network and results in fewer net hydrogen bonds. The spectra of the largest
      clusters (n = 32) are very similar, suggesting that intrinsic water properties
      are more important than ion-water interactions by that size, but subtle effects
      of Mg on surface water molecules are observed even for such large cluster sizes.

PMID- 19754187
TI  - Length dependence for intramolecular energy transfer in three- and four-color
      donor-spacer-acceptor arrays.
AB  - A series of donor-spacer-acceptor triads has been synthesized and fully
      characterized. Both donor and acceptor units are built from boron dipyrromethene
      (BODIPY) dyes but they differ in their respective conjugation lengths, and
      thereby offer quite disparate optical properties. The spacer units comprise an
      oligomer of 1,4-phenylene-diethynylene repeat units and allow the boron-boron
      separation distance to be varied progressively from 18 to 38 A. A notable feature
      of this series is that each subunit can be selectively excited with monochromatic
      light. Highly efficacious electronic energy transfer (EET) occurs from the first
      excited singlet state localized on the conventional BODIPY dye to its counterpart
      resident on the expanded BODIPY-based nucleus, but the rate constant follows a
      nonlinear evolution with separation distance. Overall, the rate of EET falls by
      only a factor of 4-fold on moving from the shortest to the longest spacer. This
      shallow length dependence is a consequence of the energy gap between donor and
      spacer units becoming smaller as the molecular length increases. Interestingly, a
      simple relationship exists between the measured electronic resistance of the
      spacer unit and the Huang-Rhys factor determined by emission spectroscopy. Both
      parameters relate to the effective conjugation length. Direct illumination of the
      spacer unit leads to EET to both terminals, followed by EET from conventional
      BODIPY to the expanded version. In each case, EET to the expanded dye involves
      initial population of the second-singlet excited state, whereas transfer from
      spacer to the conventional BODIPY dye populates the S(2) state for shorter
      lengths but the S(1) state for the longer analogues. The rate of EET from spacer
      to conventional BODIPY dye, as measured for the corresponding molecular dyads, is
      extremely fast (>10(11) s(-1)) and scales with the spectral overlap integral. The
      relative partitioning of EET from the spacer to each terminal is somewhat
      sensitive to the molecular length, with the propensity to populate the
      conventional BODIPY dye changing from 65% for N = 0 to 45% for N = 2. The most
      likely explanation for this behavior can be traced to the disparate spectral
      overlap integrals for the two dyes. These systems have been complemented by a
      molecular tetrad in which pyrene residues replace the fluorine atoms present on
      the conventional BODIPY-based dye. Here, rapid EET occurs from pyrene to the
      BODIPY dye and is followed by slower, long-range EET to the opposite terminal.
      Such materials are seen as highly attractive solar concentrators when dispersed
      in transparent plastic media and used under conditions where both inter- and
      intramolecular EET operate.

PMID- 19754188
TI  - Enhancement of hydrogen adsorption in metal-organic frameworks by the
      incorporation of the sulfonate group and Li cations. A multiscale computational
      study.
AB  - By means of ab initio methods, the effect on the H(2) storage ability of a newly
      proposed organic linker for IRMOF-14 has been studied. The linker comprises a
      negatively charged sulfonate (-SO(3)(-1)) group in combination with a Li cation.
      It is found that these two charged groups significantly increase the interaction
      energy between the hydrogen molecules and the new proposed organic linker of the
      MOF. The substituted group of the linker may host up to six hydrogen molecules
      with an average interaction energy of 1.5 kcal/mol per H(2) molecule. This value
      is three times larger than the binding energy over the bare linker that has been
      obtained from DFT calculations. GCMC atomistic simulations verified that the
      proposed material can be qualified among the highest adsorbing materials for
      volumetric capture of H(2), especially at ambient conditions. This
      functionalization strategy can be applied in many different MOF structures to
      enhance their storage abilities.

PMID- 19754189
TI  - Spectroscopic identification of the resonance-stabilized cis- and trans-1
      vinylpropargyl radicals.
AB  - The cis-1-vinylpropargyl (cis-1VPR, cis-pent-4-en-1-yn-3-yl) and trans-1
      vinylpropargyl (trans-1VPR, trans-pent-4-en-1-yn-3-yl) radicals, produced in a
      supersonically cooled hydrocarbon discharge, have been identified by a synergy of
      2-dimensional fluorescence and ionization spectroscopies, revealing their
      electronic origin transitions at 21,232 and 21,645 cm(-1) respectively. These
      assignments are supported by an excellent agreement between calculated ground
      state frequencies of cis-1VPR and trans-1VPR with those obtained by dispersed
      fluorescence spectroscopy. In addition, high-resolution rotational contours of
      the two bands are well simulated using calculated X- and A-state trans-1VPR and
      cis-1VPR rotational constants. Finally, computed origin transition energies of
      these two isomers are within several hundred wavenumbers of the observed band
      positions. With the 1-phenylpropargyl radical, the 1VPR isomers are the second 1
      substituted propargyl species to have been observed abundantly from a hydrocarbon
      discharge, while no 3-substituted analogue has been positively identified. This
      is likely due to the greater resonance stabilization energy of the 1-substituted
      species, arising from concerted delocalization of the unpaired electron over the
      vinyl and propargyl moieties.

PMID- 19754190
TI  - Synthesis and optical spectroscopy of oligo(1,6-heptadiynes) with a single basic
      structure prepared through adamantylimido-based molybdenum Wittig and metathesis
      chemistry.
AB  - Linear oligoenes of 1,6-heptadiynes (derived from dialkyl dipropargylmalonates)
      with a single basic structure and up to 23 conjugated double bonds were
      synthesized through Wittig-like reactions between bimetallic Mo-alkylidene
      compounds and aldehyde-capped oligoenes. The relatively rigid and isomerically
      pure oligoenes have structures with alternating cis,trans conjugated double bonds
      in which the cis double bond is part of a cyclopentene ring. Molecular weights
      have been confirmed through MALDI-MS measurements of samples purified by HPLC.
      Optical spectra of the purified samples show significant vibronic resolution,
      even in room temperature samples, and are remarkably similar to those of simple
      polyenes and carotenoids. Therefore, a systematic investigation of the dependence
      of the allowed electronic transition energies (electronic origins) on conjugation
      lengths has become possible. Studies of seven allowed transitions for molecules
      with 5-23 double bonds (= N) indicate asymptotic convergence (with approximately
      a 1/N dependence) to a common long polyene limit at approximately 16,000 cm(-1).
      The convergence of these electronic transitions agrees with theoretical
      treatments of polyene excited-state energies and is consistent with the
      absorption spectra of analogous diethyl dipropargylmalonate polymers (1/N
      approximately 0).

PMID- 19754191
TI  - Crystal structure of ammonia monohydrate phase II.
AB  - We have determined the crystal structure of ammonia monohydrate phase II (AMH II)
      employing a combination of ab initio computational structure prediction and
      structure solution from neutron powder diffraction data using direct space
      methods. Neutron powder diffraction data were collected from perdeuterated AMH II
      using the D2B high-resolution diffractometer at the Institut Laue-Langevin. AMH
      II crystallizes in space-group Pbca with 16 formula units in a unit-cell of
      dimensions a = 18.8285(4) A, b = 6.9415(2) A, c = 6.8449(2) A, and V = 894.61(3)
      A3 [rho(calc)(deuterated) = 1187.56(4) kg m(-3)] at 502 MPa, 180 K. The structure
      is characterized by sheets of tessellated pentagons formed by orientationally
      ordered O-D...O, O-D...N, and N-D...O hydrogen-bonds; these sheets are stacked
      along the a-axis and connected by N-D...O hydrogen bonds alone. With the
      exception of the simple body-centered-cubic high-pressure phases of ammonia
      monohydrate and ammonia dihydrate, this is the first complex molecular structure
      of any of the high-pressure stoichiometric ammonia hydrates to be determined. The
      powder structure solution is complemented by an ab initio structure prediction
      using density functional theory which gives an almost identical hydrogen bonding
      network.

PMID- 19754192
TI  - iTRAQ underestimation in simple and complex mixtures: "the good, the bad and the
      ugly".
AB  - The increasing popularity of iTRAQ for quantitative proteomics applications makes
      it necessary to evaluate its relevance, accuracy, and precision for biological
      interpretation. Here, we have assessed (a) the accuracy and precision of iTRAQ
      quantification in a controlled experimental setup, using low- and high-complexity
      protein mixtures; and (b) the potential pitfalls that hamper the applicability
      and attainable dynamic range of iTRAQ: isotopic contamination, background
      interference, and signal-to-noise ratio. Our data suggest greater dynamic
      crosstalk between interfering factors affecting underestimations, and that these
      interferences were largely scenario-specific, dependent on sample complexity. The
      good is the potential for iTRAQ to provide accurate quantification spanning 2
      orders of magnitude. This potential is however limited by two factors. (1) The
      bad: the existence of isotopic impurities that can be corrected for; provided
      accurate isotopic factors are at one's disposal. (2) The ugly: we demonstrate
      here the interference of mixed MS/MS contribution occurring during precursor
      selection, an issue that is currently very difficult to minimize. In light of our
      results, we propose a list of advice for iTRAQ data analysis that could routinely
      ameliorate quantitative interpretation of proteomic data sets.

PMID- 19754193
TI  - Characterizations of environmental factors in conjugated linoleic acid production
      by mixed rumen bacteria.
AB  - Conjugated linoleic acid (CLA) production by rumen bacteria is closely related to
      biohydrogenation of linoleic acid (LA) and affected by various environmental
      factors. Ruminal biohydrogenation and isomerization were characterized in view of
      incubation conditions using a mixed culture of microorganisms obtained from
      surgically prepared cows. Free-floating bacteria (FFB) produced more CLA than
      particle-attached bacteria (PAB). Some major factors affecting the ruminal
      environment such as diet, concentrations of fat substrates, incubation time, pre
      incubation, and the presence of glucose in the medium were found to be important
      determinants for the ruminal production of CLA and in a close relationship with
      biohydrogenation. The mixed bacterial culture, which was pre-exposed to LA,
      produced more CLA than an unexposed control in a medium containing 30% rumen
      fluid. The rate of conversion of fat substrate (LA) to hydrogenated products
      (trans-C18:1, C18:0) was negatively correlated with the initial LA concentration.
      Overall, the present study showed that CLA accumulation can be increased by
      modification of diet-induced environmental conditions, which affect changes in
      ruminal microflora.

PMID- 19754194
TI  - Micro/nanobinary structure of silver films on copper alloys with stable water
      repellent property under dynamic conditions.
AB  - Facile galvanic replacement was adopted to grow cauliflower-like and dendrite
      coral-like silver films on commercial copper alloy substrates. Both types of
      silver films possess micro/nanobinary structures, the formation and evolution of
      which are achieved through the oriented attachment growth mechanism. After
      modification by a monolayer of n-dodecanethiol, the cauliflower-like silver film
      becomes hydrophobic with a contact angle (CA) of 115 +/- 1 degrees and a CA
      hysteresis of 74 +/- 1 degrees and the dendrite coral-like silver film exhibits
      the extreme hydrophobicity characterized by a CA of 158 +/- 1 degrees and a CA
      hysteresis of less than 2 +/- 1 degrees . Furthermore, the bouncing property of
      millimeter-sized water droplets on the modified dendrite coral-like silver
      surface is much better than that on the modified cauliflower-like silver surface.
      The different wetting property between the two silver films is attributed to the
      surface roughness. Larger surface roughness provided by the dendrite coral-like
      silver film means more air pockets, among the micro/nanobinary structures, that
      bounce water droplets back more strongly. The dynamic bouncing behavior of water
      droplets, such as restitution coefficient and contact time, on the
      superhydrophobic modified cauliflower-like silver surface was also investigated
      at different impact velocities.

PMID- 19754195
TI  - Plantain (Plantago L.) species as novel sources of flavonoid antioxidants.
AB  - To examine the antioxidant properties of methanol extracts of selected Plantago
      species (P. argentea Chaix., P. holosteum Scop., P. major L., P. maritima L., and
      P. media L.), various assays that measure free radical scavenging ability were
      carried out: DPPH, hydroxyl radical, superoxide anion, and nitric oxide scavenger
      capacity tests, reducing power (FRAP) assay, and Fe(2+)/ascorbate induced lipid
      peroxidation. In all of the tests extracts showed a potent antioxidant effect
      compared with BHT, a well-known synthetic antioxidant, and the extract of P.
      major, accepted as an official remedy. Besides, in examined extracts the total
      phenolic amount (ranging from 38.43 to 70.97 mg of GAE/g of dw) and the total
      flavonoid content (5.31-13.10 mg of QE/g of dw) were determined. Furthermore, the
      presence and content of selected flavonoids (luteolin-7-O-glucoside, apigenin-7-O
      glucoside, luteolin, apigenin, rutin, and quercetin) were studied using LC-MS/MS
      technique. LC-MS/MS analysis showed noticeable qualitative and quantitative
      differences between the species according to which the examined Plantago species
      could be regarded as a possible new source of natural antioxidants. In this study
      three of the species examined, P. maritima, P. argentea, and P. holosteum, have
      been analyzed for the first time.

PMID- 19754196
TI  - Betulinic acid, a natural pentacyclic triterpenoid, prevents abdominal fat
      accumulation in mice fed a high-fat diet.
AB  - In the search for potential antiobese agents from natural sources, this study
      investigated the effects of betulinic acid (BA), a pentacyclic triterpene from
      Clusia nemorosa L. (Clusiaceae), in mice on a high-fat diet (HFD). Adult male
      Swiss mice (n = 8) treated or not with BA (50 mg/L, in drinking water) were fed a
      HFD during 15 weeks. Mice treated with BA and fed a HFD showed significantly (P <
      0.05) decreased body weights, abdominal fat accumulation, blood glucose, plasma
      triglycerides, and total cholesterol relative to their respective controls fed no
      BA. Additionally, BA treatment, while significantly elevating the plasma hormone
      levels of insulin and leptin, decreased the level of ghrelin. However, it caused
      a greater decrease in plasma amylase activity than the lipase. These findings
      suggest that BA has an antiobese potential through modulation of fat and
      carbohydrate metabolism, and it may be a suitable lead compound in the treatment
      of obesity.

PMID- 19754197
TI  - Preparation, characterization and scanned conductance microscopy studies of DNA
      templated one-dimensional copper nanostructures.
AB  - The synthesis of one-dimensional metal nanostructures can be achieved through the
      use of DNA molecules as templates to control and direct metal deposition. Copper
      nanostructures have been fabricated using this strategy, through association of
      Cu(2+) ions to DNA templates and reduced with ascorbic acid. Due to the
      possibility that the reduction of the Cu(2+) can result in the preferential
      formation of Cu(2)O over metallic Cu(0), X-ray photoelectron spectroscopy and X
      ray diffraction have been carried out to establish the chemical identity of the
      nanostructures. Conclusive evidence is found that reduction of the Cu(2+) ions
      does result in the formation of the desired metallic Cu(0) structures. The
      morphology of the nanostructured Cu(0) material has also been observed by atomic
      force microscopy, showing the structures to have a "beads-on-a-string" appearance
      and being 3.0-5.5 nm in height. The electrical properties of the structures have
      been investigated by scanned conductance microscopy, showing the Cu(0) structures
      exhibit much larger electrical resistance than expected for a metallic nanowire.
      This is thought to be a consequence of their "beads-on-a-string" morphology and
      small lateral dimensions (sub-10 nm); both these factors would be expected to
      increase the electron scattering rate, and, further, there are likely to be
      significant tunneling barriers at the Cu(0) particle-particle junctions.

PMID- 19754198
TI  - Identification and characterization of a small molecule inhibitor of Fatty Acid
      binding proteins.
AB  - Molecular disruption of the lipid carrier AFABP/aP2 in mice results in improved
      insulin sensitivity and protection from atherosclerosis. Because small molecule
      inhibitors may be efficacious in defining the mechanism(s) of AFABP/aP2 action, a
      chemical library was screened and identified 1 (HTS01037) as a pharmacologic
      ligand capable of displacing the fluorophore 1-anilinonaphthalene 8-sulfonic acid
      from the lipid binding cavity. The X-ray crystal structure of 1 bound to
      AFABP/aP2 revealed that the ligand binds at a structurally similar position to a
      long-chain fatty acid. Similar to AFABP/aP2 knockout mice, 1 inhibits lipolysis
      in 3T3-L1 adipocytes and reduces LPS-stimulated inflammation in cultured
      macrophages. 1 acts as an antagonist of the protein-protein interaction between
      AFABP/aP2 and hormone sensitive lipase but does not activate PPARgamma in
      macrophage or CV-1 cells. These results identify 1 as an inhibitor of fatty acid
      binding and a competitive antagonist of protein-protein interactions mediated by
      AFABP/aP2.

PMID- 19754199
TI  - Identification of N-(5-tert-butyl-isoxazol-3-yl)-N'-{4-[7-(2-morpholin-4-yl
      ethoxy)imidazo[2,1-b][1,3]benzothiazol-2-yl]phenyl}urea dihydrochloride (AC220),
      a uniquely potent, selective, and efficacious FMS-like tyrosine kinase-3 (FLT3)
      inhibitor.
AB  - Treatment of AML patients with small molecule inhibitors of FLT3 kinase has been
      explored as a viable therapy. However, these agents are found to be less than
      optimal for the treatment of AML because of lack of sufficient potency or
      suboptimal oral pharmacokinetics (PK) or lack of adequate tolerability at
      efficacious doses. We have developed a series of extremely potent and highly
      selective FLT3 inhibitors with good oral PK properties. The first series of
      compounds represented by 1 (AB530) was found to be a potent and selective FLT3
      kinase inhibitor with good PK properties. The aqueous solubility and oral PK
      properties at higher doses in rodents were found to be less than optimal for
      clinical development. A novel series of compounds were designed lacking the
      carboxamide group of 1 with an added water solubilizing group. Compound 7 (AC220)
      was identified from this series to be the most potent and selective FLT3
      inhibitor with good pharmaceutical properties, excellent PK profile, and superior
      efficacy and tolerability in tumor xenograft models. Compound 7 has demonstrated
      a desirable safety and PK profile in humans and is currently in phase II clinical
      trials.

PMID- 19754200
TI  - Novel triazole ribonucleoside down-regulates heat shock protein 27 and induces
      potent anticancer activity on drug-resistant pancreatic cancer.
AB  - A series of novel 3-arylethynyltriazolyl ribonucleosides were synthesized and
      assessed for their anticancer activity on the drug-resistant pancreatic cancer
      cell line MiaPaCa-2. Among them, one compound exhibited potent apoptosis-inducing
      properties and anticancer activity against the pancreatic cancer model MiaPaCa-2
      both in vitro and in vivo with no adverse effects. This compound did not inhibit
      DNA synthesis and therefore does not resemble the clinical drug gemcitabine. It
      did, however, significantly down-regulate the expression of heat shock protein 27
      (Hsp27), a small molecular chaperone playing an important role in drug resistance
      and highly expressed in drug-resistant cancer forms, and thus represents the
      first small molecular anticancer lead with such a mode of action.

PMID- 19754201
TI  - Physical binding pocket induction for affinity prediction.
AB  - Computational methods for predicting ligand affinity where no protein structure
      is known generally take the form of regression analysis based on molecular
      features that have only a tangential relationship to a protein/ligand binding
      event. Such methods have limited utility when structural variation moves beyond
      congeneric series. We present a novel approach based on the multiple-instance
      learning method of Compass, where a physical model of a binding site is induced
      from ligands and their corresponding activity data. The model consists of
      molecular fragments that can account for multiple positions of literal protein
      residues. We demonstrate the method on 5HT1a ligands by training on a series with
      limited scaffold variation and testing on numerous ligands with variant
      scaffolds. Predictive error was between 0.5 and 1.0 log units (0.7-1.4 kcal/mol),
      with statistically significant rank correlations. Accurate activity predictions
      of novel ligands were demonstrated using a validation approach where a small
      number of ligands of limited structural variation known at a fixed time point
      were used to make predictions on a blind test set of widely varying molecules,
      some discovered at a much later time point.

PMID- 19754202
TI  - Cause and effect of melittin-induced pore formation: a computational approach.
AB  - Melittin embedded in a palmitoyl oleyl phosphatidylcholine bilayer at a high
      peptide/lipid ratio (1:30) was simulated in the presence of explicit water and
      ions. The simulation results indicate the incipience of an ion-permeable water
      pore through collective membrane perturbation by bound peptides. The positively
      charged residues of melittin not only act as "anchors" but also disrupt the
      membrane, leading to cell lysis. A detailed analysis of the lipid tail order
      parameter profile depicts localized membrane perturbation. The lipids in the
      vicinity of the aqueous cavity adopt a tilted conformation, which allows local
      bilayer thinning. The prepore thus formed can be considered as the melittin
      induced structural defects in the bilayer membrane. Because of the strong
      cationic nature, the melittin-induced prepore exhibits selectivity toward anions
      over cations. As Cl(-) ions entered into the prepore, they are electrostatically
      entrapped by positively charged residues located at its wall. The confined motion
      of the Cl(-) ions in the membrane interior is obvious from calculated diffusion
      coefficients. Moreover, reorientation of the local lipids occurs in such a way
      that few lipid heads along with peptide helices can line the surface of the
      penetrating aqueous phase. The flipping of lipids argued in favor of melittin
      induced toroidal pore over a barrel-stave mechanism. Thus, our result provides
      atomistic level details of the mechanism of membrane disruption by antimicrobial
      peptide melittin.

PMID- 19754203
TI  - Novel twist on the biotin switch cracks endothelial cell S-nitrosoproteome.

PMID- 19754204
TI  - Asymmetries in transition metal XPS spectra: metal nanoparticle structure, and
      interaction with the graphene-structured substrate surface.
AB  - Transition-metal XPS spectra have traditionally been considered to possess a
      natural asymmetry, extending to the high-binding-energy side. This is based on
      the fact that these spectra have generally been found experimentally to have such
      an asymmetry, as well as on the confirmation of asymmetry offered by the Doniach
      Sunjic equation, an equation based on the proposal that the conduction electron
      scattering amplitude for interband absorption or emission in metals, at the Fermi
      level, is a singularity. Our discovery that metal nanoparticles, prepared under
      vacuum and characterized without exposure to air, have symmetric peaks, which
      become asymmetric with time, informed us that these peak asymmetries have other
      sources. On the basis of our belief that all metal spectra are composed of
      symmetric peaks, where the asymmetries are attributed to overlapping minor peaks
      that are consistent with known physical and chemical phenomena associated with
      that metal, we have shown that, for the metals that we have studied, these
      asymmetries contain much information, otherwise unavailable, on the structures,
      contaminants, oxidation, and interfacial interactions of nanoparticle surfaces.
      The existence of this information has been demonstrated for several metals, and
      its value is shown by its use in explaining the strong interfacial bonding of the
      nanoparticles with substrates having graphene structures. A possible future
      research direction is offered in the field of metal-metal interactions in
      nanoparticle alloys.

PMID- 19754205
TI  - Cell-targeted self-assembled DNA nanostructures.
AB  - We present two strategies for attaching self-assembled DNA arrays to the surfaces
      of cells. Our first approach uses biotin-streptavidin interactions to bind DNA
      architectures to biotinylated cells. The second approach takes advantage of
      specific antibody-cell surface interactions, conjugated arrays and the subsequent
      binding to native epidermal growth factor receptors expressed on cancer cells.
      DNA array-cell surface interactions were visualized by fluorescence, confocal
      microscopy, and scanning electron microscopy. This novel application of DNA
      nanoarrays provides strategies to specifically label cell surfaces with
      micrometer-sized patches, bind cells onto a designed functionalized DNA scaffold,
      engineer cell/cell networks into microtissues, and deliver materials to cell
      surfaces.

PMID- 19754206
TI  - Structure sensitivity of methanol electrooxidation on transition metals.
AB  - We have investigated the structure sensitivity of methanol electrooxidation on
      eight transition metals (Au, Ag, Cu, Pt, Pd, Ir, Rh, and Ni) using periodic, self
      consistent density functional theory (DFT-GGA). Using the adsorption energies of
      16 intermediates on two different facets of these eight face-centered-cubic
      transition metals, combined with a simple electrochemical model, we address the
      differences in the reaction mechanism between the (111) and (100) facets of these
      metals. We investigate two separate mechanisms for methanol electrooxidation: one
      going through a CO* intermediate (the indirect pathway) and another that oxidizes
      methanol directly to CO(2) without CO* as an intermediate (the direct pathway). A
      comparison of our results for the (111) and (100) surfaces explains the origin of
      methanol electrooxidation's experimentally-established structure sensitivity on
      Pt surfaces. For most metals studied, on both the (111) and (100) facets, we
      predict that the indirect mechanism has a higher onset potential than the direct
      mechanism. Ni(111), Au(100), and Au(111) are the cases where the direct and
      indirect mechanisms have the same onset potential. For the direct mechanism, Rh,
      Ir, and Ni show a lower onset potential on the (111) facet, whereas Pt, Cu, Ag,
      and Au possess lower onset potential on the (100) facet. Pd(100) and Pd(111) have
      the same onset potential for the direct mechanism. These results can be
      rationalized by the stronger binding energy of adsorbates on the (100) facet
      versus the (111) facet. Using linear scaling relations, we establish reactivity
      descriptors for the (100) surface similar to those recently developed for the
      (111) surface; the free energies of adsorbed CO* and OH* can describe methanol
      electrooxidation trends on various metal surfaces reasonably well.

PMID- 19754207
TI  - Clinical feasibility of microscopically-guided breast needle biopsy using a fiber
      optic probe with computer-aided detection.
AB  - Needle biopsy of small or nonpalpable breast lesions has a high nondiagnostic
      sampling rate even when needle position is guided by stereotaxis or ultrasound.
      We assess the feasibility of using a near-infrared fiber optic probe and computer
      aided detection for the microscopic guidance of needle breast biopsy procedures.
      Specimens from nine consented patients undergoing breast-conserving surgery were
      assessed intraoperatively using a needle device with an integrated fiber-optic
      probe capable of assessing two physical tissue properties highly correlated to
      pathology. Immediately following surgical resection, specimens were probed by
      inserting the optical biopsy needle device into the tissue, simulating the
      procedure used to position standard biopsy needles. Needle positions were marked
      and correlated with histology, which verified measurements obtained from 58
      needle positions, including 40 in adipose and 18 in tumor tissue. This study
      yielded tissue classifications based on measurement of optical refractive index
      and scattering. Confidence-rating schemes yielded combined sensitivity of 89%
      (16/18) and specificity of 78% (31/40). Refractive index tests alone identified
      tumor tissue with a sensitivity of 83% (15/18) and specificity of 75% (30/40).
      Scattering profiles independently identified tumor tissue with a sensitivity of
      61% (11/18) and specificity of 60% (24/40). These results show that a biopsy
      needle with an integrated fiber optic probe can be used to identify breast tumor
      tissue for sampling. Integration of this probe into current practices offers the
      potential to reduce nondiagnostic sampling rates by directly evaluating in situ
      microscopic tissue properties in real-time, before removal.

PMID- 19754208
TI  - Protein profiling of pleural effusions to identify malignant pleural mesothelioma
      using SELDI-TOF MS.
AB  - Diagnosis of malignant pleural mesothelioma (MM) is limited. Novel proteomic
      techno_logies can be utilized to discover changes in expression of pleural
      proteins that might have diagnostic value. The objective of this study was to
      detect protein profiles that could be used to identify malignant pleural
      mesothelioma with surface enhanced laser desorption/ionization time-of-flight
      (SELDI-TOF) mass spectrometry (MS). Pleural effusions were collected from
      patients with confirmed mesothelioma (n = 41) and from patients with effusions
      due to other causes ([n = 48] cancerous and non-cancerous). Samples were
      fractionated using anion exchange chromatography and bound to different types of
      ProteinChip array surfaces. All samples were also subjected to other commercially
      available immunoassays (human epididymes protein 4 [HE4], osteopontin [OPN],
      soluble mesothelin-related proteins [SMRP], and the cytokeratin 19 fragment
      [CYFRA 21-1]). Peak intensity data obtained by SELDI-TOF were subjected to
      classification algorithms in order to identify potential classifier peaks. A
      protein peak at m/z 6614 was characterized as apolipoprotein (Apo) CI. In this
      setting, the sensitivity and specificity of this potential biomarker was 76 % and
      69 %, respectively. The area under the receiver operating characteristic curve
      (AUC) for Apo CI was 0.755, thereby outperforming OPN, HE4, and CYFRA 21-1. SMRP
      performed best with an AUC of 0.860 with a sensitivity of 83% and specificity of
      74%. Our study validates the use of SMRP as a diagnostic marker for pleural
      mesothelioma and furthermore suggests that Apo CI levels could be used in the
      future to discriminate pleural mesothelioma from other causes of exudates.

PMID- 19754209
TI  - A computational approach for the identification of small GTPases based on
      preprocessed amino acid sequences.
AB  - The prediction of essential biological features based on a given protein sequence
      is a challenging task in computational biology. To limit the amount of in vitro
      verification, the prediction of essential biological activities gives the
      opportunity to detect so far unknown sequences with similar properties. Besides
      the application within the identification of proteins being involved in
      tumorigenesis, other functional classes of proteins can be predicted. The
      prediction accuracy depends on the selected machine learning approach and even
      more on the composition of the descriptor set used. A computational approach
      based on feedforward neural networks was applied for the prediction of small
      GTPases. Consequently, this was realized by taking secondary structure and
      hydrophobicity information as a preprocessing architecture and thus, as
      descriptors for the neural networks. We developed a neural network cluster, which
      consists of a filter network and four subfamily networks. The filter network was
      trained to identify small GTPases and the subfamily networks were trained to
      assign a small GTPase to one of the subfamilies. The accuracy of the prediction,
      whether a given sequence represents a small GTPase is very high (98.25%). The
      classifications of the subfamily networks yield comparable accuracy. The high
      prediction accuracy of the neural network cluster developed, gives the
      opportunity to suggest the use of hydrophobicity and secondary structure
      prediction in combination with a neural network cluster, as a promising method
      for the prediction of essential biological activities.

PMID- 19754210
TI  - Megavoltage CT in helical tomotherapy - clinical advantages and limitations of
      special physical characteristics.
AB  - Helical tomotherapy is a form of image-guided intensity-modulated radiotherapy
      that introduces the ring gantry concept into radiation oncology. The system is a
      combination of a therapeutic linear accelerator and a megavoltage CT-scanner.
      This work describes the clinical experience with megavoltage CT with 456 patients
      in more than 11000 fractions. It also provides a review of the current literature
      of the possibilities and limitations of megavoltage CT. Between July 2006 and
      October 2008 456 patients were treated with helical tomotherapy and a
      pretreatment megavoltage CT was performed in 98.1% of the 11821 fractions to
      perform position control and correction. CT image acquisition was done with 3.5
      MV x-rays in the helical tomotherapy machine. MVCT was used for dose
      recalculations to quantify doses distributions in cases of changing geometry,
      tumor shrinkage or presence of metal implants. Inverse treatment planning for
      prostate cancer patients with bilateral hip replacements was performed based upon
      an MVCT. A mean 3D-correction vector of 7.1mm with a considerable variation was
      detected and immediately corrected. Mean shifts were lateral 0.9mm (sd 5.0mm),
      mean longitudinal shift 1.0mm (sd 5.1mm) and mean vertical shift 3.2mm (sd
      5.2mm). The MVCT enables imaging of anatomical structures in the presence of
      dental metal or orthopedic implants. Especially in these cases, dose
      recomputations can increase the precision of dose calculations. Due to a mean 3d
      correction vector of more than 7mm and a variation of corrections of more than
      5mm daily image-guidance is recommended to achieve a precise dose application.
      The MVCT shows evident advantages in cases with metal implants but has
      limitations due to a reduced soft tissue contrast. Compared with megavoltage cone
      beam-CT the tomotherapy fan beam CT adds less extra dose fore the patient and has
      a better soft tissue contrast.

PMID- 19754211
TI  - Helical tomotherapy with simultaneous integrated boost for high-risk and lymph
      node-positive prostate cancer: early report on acute and late toxicity.
AB  - The use of whole pelvic radiotherapy (WPRT) for high-risk and lymph node-positive
      prostate cancer (PC) remains controversial. The purpose of this study was to
      evaluate the acute toxicity associated with helical tomotherapy in the treatment
      of high-risk and lymph node-positive prostate cancer. To do so, twenty-eight
      patients were treated to a dose of 54 Gy in daily fractions of 1.8 Gy to the
      pelvic lymph node area, while the prostate and the seminal vesicles received a
      simultaneous integrated boost (SIB) to a dose of 70.5 Gy. A SIB to a dose of 60
      Gy was delivered to the involved lymph node region(s) in 8 patients with pelvic
      lymph node metastases. All patients received concurrent hormonal treatment. The
      incidence of grade 2 and 3 acute gastrointestinal (GI) toxicity was 7% and 0%
      respectively. Grade 2 and 3 acute genito-urinary (GU) side effects were observed
      in 14% and 4% of the patients respectively. No grade 4 side effects occurred. No
      increased toxicity was observed in the 8 lymph node-positive patients receiving a
      simultaneous pelvic nodal dose escalation. In conclusion, WPRT with a SIB to the
      prostate and seminal vesicles by helical tomotherapy resulted in a favourable
      toxicity profile. Pelvic nodal dose escalation in node-positive patients is
      feasible without increasing toxicity.

PMID- 19754212
TI  - Dosimetric comparison of intensity-modulated radiosurgery and helical tomotherapy
      for the treatment of multiple intracranial metastases.
AB  - The purpose of this study was to evaluate the dosimetry of single fraction,
      single-isocenter intensity-modulated radiosurgery (IMRS) plans for multiple
      intracranial metastases and to compare Helical Tomotherapy (HT). Ten treatment
      plans with 3-6 brain metastases treated with IMRS were re-planned with HT. The
      mean number of lesions was 5 and mean PTV 22 cm(3). The prescribed dose was 16-20
      Gy. The mean V100% was similar for IMRS and HT, and the mean conformity index was
      1.4, mean Paddick confirmity index was 0.7, and mean MDPD was 1.1 for both. The
      mean gradient index was similar for both. The mean 50% _isodose volume was 179.2
      cm(3) for IMRS and 277.0 cm(3) for HT (p=0.01). The mean maximum doses to organs
      at risk were lower for IMRS except brainstem and right optic nerve. For brain,
      the integral dose was 5.1 and 6.8 Gy-kg (p<0.001) and mean dose 4.0 and 5.4 Gy
      (p<0.001) for IMRS and HT, respectively. The mean treatment times were 23 (IMRS)
      and 41 (HT) minutes. Conformity and homogeneity indices were equivalent and
      sparing of the organs at risk was clinically acceptable for both IMRS and HT.
      Though the gradient index was similar for IMRS and HT, the mean 50% isodose
      volume and integral dose to normal brain were lower for IMRS as was treatment
      time.

PMID- 19754213
TI  - Dosimetric comparisons of three-dimensional conformal radiotherapy, intensity
      modulated radiotherapy, and helical tomotherapy in whole abdominopelvic
      radiotherapy for gynecologic malignancy.
AB  - OBJECTIVES: The goal of this study was to dosimetrically compare 3-dimensional
      radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT), and helical
      tomotherapy (TOMO) plans for whole abdominopelvic radiotherapy (WART) in patients
      with gynecologic cancer. METHODS: Ten patients were selected for WART planning.
      Doses were prescribed to planning target volumes (PTVs) as the followings: 30 Gy
      to PTV-whole abdominopelvis (PTV-WA), 40 Gy to PTV-para-aortic lymph node (PTV
      PALN), 44 Gy to PTV-pelvis, and 50 Gy to gross target volume (GTV) in 20
      fractions. Dose to whole liver, both kidneys, and spinal cord were constrained
      below each tissue tolerance, and bone marrow (BM)-sparing technique was adopted
      in IMRT and TOMO. Dosimetric parameters and treatment times were compared among
      plans. RESULTS: Calculated doses in TOMO came most closely to the prescribed dose
      for coverage of PTV-WA, PTV-PALN, PTV-pelvis, and GTV compared to 3DCRT, and
      IMRT. In normal organs, TOMO had significantly better dosimetric profiles
      compared to IMRT and 3DCRT. TOMO significantly reduced V(20Gy), and mean dose of
      whole liver, both kidneys, and spinal cord. The use of BM-sparing technique (BMS)
      did not impair coverage of target volume in IMRT and TOMO. While IMRT showed no
      differences of irradiated BM dose using BMS, TOMO with BMS reduced half V(20Gy)
      of BM compared to TOMO without BMS. CONCLUSIONS: TOMO showed dosimetric
      superiority in target coverage, sparing BM, and other normal organs compared to
      3DCRT and IMRT. Clinical experiences will be needed for evaluation of feasibility
      of WART using TOMO in patients with gynecologic cancer.

PMID- 19754214
TI  - Helical tomotherapy significantly reduces dose to normal tissues when compared to
      3D-CRT for locally advanced rectal cancer.
AB  - Combined modality treatment (neoadjuvant chemoradiotherapy followed by surgery)
      for locally advanced rectal cancer requires special attention to various organs
      at risk (OAR). As a result, the use of conformal dose delivery methods has become
      more common in this disease setting. Helical tomotherapy is an image-guided
      intensity modulated delivery system that delivers dose in a fan-beam manner at 7
      degree intervals around the patient and can potentially limit normal tissue from
      high dose radiation while adequately treating targets. In this study we
      dosimetrically compare helical tomotherapy to 3D-CRT for stage T3 rectal cancer.
      The helical tomotherapy plans were optimized in the TomoPlan system to achieve an
      equivalent uniform dose of 45 Gy for 10 patients with T3N0M0 disease that was at
      least 5cm from the anal verge. The GTV included the rectal thickening and mass
      evident on colonoscopy and CT scan as well as with the help of a colorectal
      surgeon. The CTV included the internal iliac, obturator, and pre-sacral lymphatic
      chains. The OAR that were outlined included the small bowel, pelvic bone marrow,
      femoral heads, and bladder. Anatom-e system was used to assist in delineating
      GTV, CTV and OAR. These 10 plans were then duplicated and optimized into 3-field
      3D-CRT plans within the Pinnacle planning system.The V[45], V[40], V[30], V[20],
      V[10], and mean dose to the OAR were compared between the helical tomotherapy and
      3D-CRT plans. Statistically significant differences were achieved in the doses to
      all OAR, including all volumes and means except for V[10] for the small bowel and
      the femoral heads. Adequate dosimetric coverage of targets were achieved with
      both helical tomotherapy and 3D-CRT. Helical tomotherapy reduces the volume of
      normal tissue receiving high-dose RT when compared to 3D-CRT treatment. Both
      modalities adequately dose the tumor. Clinical studies addressing the dosimetric
      benefits are on-going.

PMID- 19754215
TI  - Stereotactic body radiotherapy: an emerging treatment approach for localized
      prostate cancer.
AB  - Here we report results from the first cohort of over 100 patients treated with
      hypofractionated, stereotactic body radiotherapy (SBRT) for early stage prostate
      cancer. Between February 2005 and December 2006, 112 patients with localized,
      biopsy-proven adenocarcinoma of the prostate (clinical stage T1cN0M0 to T2cN0M0)
      were treated in Naples, FL on a CyberKnife system (Accuray Incorporated,
      Sunnyvale, CA). Eighty-one patients had a Gleason score of 3+3. Mean initial PSA
      was 6.0, and mean initial prostate volume was 46.3cc. Implanted gold fiducials
      were used for image-guided targeting and tracking. Patients received 35-36 Gy
      administered in 5 consecutive fractions to the prostate and the proximal seminal
      vesicles, as identified on CT and MRI scans. At a median follow-up of 24 months,
      the mean PSA value was 0.78 ng/ml. Two patients have developed biopsy-confirmed
      local relapse; one developed distant metastases. Acute side effects were
      generally mild and resolved shortly after treatment. A single Grade 3 rectal
      complication was reported (bleeding). Eighty-two percent of patients who were
      sexually potent before treatment maintained erectile function post-treatment.
      Additional follow-up is required to better evaluate potential late toxicity and
      long-term PSA outcomes.

PMID- 19754216
TI  - Stereotactic body radiosurgery for pelvic relapse of gynecologic malignancies.
AB  - Clinical management of pelvic relapses from gynecologic malignancies remains
      challenging. Bulky pelvic relapses often lead to symptomatic cancer-related
      complications and poor clinical outcomes. Options may be limited by prior
      surgical, chemotherapeutic, and radiation treatment. Stereotactic body
      radiosurgery is a novel treatment modality which allows high radiation dose
      delivery in a non-coplanar fashion with sub-millimeter precision utilizing a
      linear accelerator mounted on a robotic arm. This study details our clinical
      experience with stereotactic body radiosurgery for treatment of patients with
      pelvic relapses of gynecologic malignancies after prior pelvic radiation.

PMID- 19754217
TI  - Progress towards therapeutic application of RNA interference for HIV infection.
AB  - HIV-1 infection is the cause of acquired immune deficiency syndrome (AIDS).
      Highly active antiretroviral therapy (HAART) has been successful in reducing the
      rate of progression to AIDS, but a cure has not yet been achieved. New tools are
      required to delay progression of infection or to block the replication cycle of
      HIV. RNA interference (RNAi) has the potential to work as a powerful tool against
      HIV infection. The mode of action of small interfering RNAs (siRNAs) against
      their target genes is through sequence complementarity, which in turn results in
      target degradation. siRNAs are showing enormous potential to be used as a
      therapeutic tool in various diseases; however, this technology still requires
      refinement before its full potential can be utilized for the development of HIV
      therapies.

PMID- 19754218
TI  - Therapeutic breast cancer vaccines: a new strategy for early-stage disease.
AB  - Treatment of breast cancer in the adjuvant setting has changed rapidly over the
      last few years. In addition to improvements in chemotherapy, radiation, hormone
      manipulation, and surgery, immunotherapy has emerged as an effective adjunct for
      the treatment of breast cancer. Passive immunotherapeutic agents such as
      trastuzumab have been widely adopted as the standard of care for HER-2/neu
      overexpressing breast cancer. Vaccine therapy in the metastatic setting has yet
      to demonstrate clinical significance in a phase III testing. This may be due to
      the enhanced immunosuppressive effects demonstrated in the tumor
      microenvironment. Lack of co-stimulatory molecules, activation of the cytotoxic T
      lymphocyte antigen-4 (CTLA-4), increased T regulatory cells as well as soluble
      immunosuppressive factors produced by the tumor contribute to the ineffectiveness
      of vaccine therapy. Based on these observations, there has been a shift towards
      treating patients with minimal residual disease and a high risk of relapse. In
      this adjuvant setting, immune mechanisms of tumor evasion are less formidable,
      and the use of vaccine therapy in these patients may offer a higher chance of
      clinical benefit. There are several different vaccine approaches, including the
      use of cell-based vaccines (autologous, allogeneic, or dendritic cell-based),
      tumor-associated peptide or protein vaccines, DNA vaccines, heat shock proteins,
      and recombinant technology using viral or bacterial vectors to enhance
      immunogenicity of vaccine preparations. This review summarizes principles
      involving vaccine formulation and antigen selection, followed by a brief synopsis
      of therapeutic vaccines given in the metastatic setting and possible reasons for
      their lack of efficacy. The current literature regarding vaccine development for
      the treatment of breast cancer in the adjuvant setting is also reviewed.

PMID- 19754219
TI  - Monoclonal antibodies targeting vascular endothelial growth factor: current
      status and future challenges in cancer therapy.
AB  - The use of monoclonal antibodies targeting the vascular endothelial growth factor
      (VEGF) pathway has been a significant addition to cancer therapy. One of the VEGF
      family members, VEGF-A (commonly referred to as VEGF), has been demonstrated to
      be important in angiogenesis. Although the mechanism of action of these
      antibodies is still under study, the anti-VEGF antibody bevacizumab has been
      approved for treatment of various solid cancers including colorectal, lung, and
      breast cancers as well as glioblastoma and renal cell carcinoma. Addition of
      bevacizumab to chemotherapy as adjuvant therapy in colorectal cancer did not
      improve disease-free survival. Bevacizumab is being tested in other clinical
      settings such as adjuvant therapy, maintenance therapy, and in combination with
      both chemotherapy and other targeted agents such as the epidermal growth factor
      receptor kinase inhibitor erlotinib. In addition to bevacizumab, other antibody
      based therapies targeting the VEGF pathway are being tested. Ramucirumab and IMC
      18F1 are monoclonal antibodies that target the VEGF receptors VEGFR-2 and VEGFR
      1, respectively. Aflibercept (VEGF-Trap), a peptide-antibody fusion targeting
      VEGF ligand, is being tested in clinical trials. Much research is focused on
      identifying biomarkers to predict which patients will benefit from anti-VEGF
      therapy. Recent results suggest that VEGF single nucleotide polymorphisms may be
      predictive of patient response to bevacizumab. Improved imaging modalities such
      as dynamic contrast-enhanced MRI (DCE-MRI) can better characterize the efficacy
      of anti-angiogenic agents. As anti-VEGF treatments such as bevacizumab have been
      integrated into the treatment of many different types of cancers, the development
      of bevacizumab-resistant tumors has become more common. Recent studies show that
      targeting other angiogenesis signaling pathways such as platelet-derived growth
      factor-C (PDGF-C), Bombina variagata peptide 8 (Bv8, also known as prokineticin
      2), and VEGFR-3 may lead to enhanced response in anti-VEGF resistant tumors. In
      the future, tailored treatments consisting of combinations of chemotherapy, other
      targeted therapies, and anti-angiogenesis agents will hopefully result in better
      patient outcomes.

PMID- 19754220
TI  - RNA interference technologies and therapeutics: from basic research to products.
AB  - RNA interference (RNAi) is a natural cellular process that regulates gene
      expression by a highly precise mechanism of sequence-directed gene silencing at
      the stage of translation by degrading specific messenger RNAs or blocking
      translation. In recent years, the use of RNAi for therapeutic applications has
      gained considerable momentum. It has been suggested that most of the novel
      disease-associated targets that have been identified are not 'druggable' with
      conventional approaches. However, any disease-causing gene and any cell type or
      tissue can potentially be targeted with RNAi. This review focuses on the current
      knowledge of RNAi mechanisms and the safety issues associated with its potential
      use in a therapeutic setting. Some of the most important aspects to consider when
      working towards the application of RNAi-based products in a clinical setting have
      been related to achieving high efficacies and enhanced stability profiles through
      a careful design of the nucleic acid sequence and the introduction of chemical
      modifications, but most of all, to developing improved delivery systems, both
      viral and non-viral. These new delivery systems allow for these products to reach
      the desired target cells, tissues or organs in a highly specific manner and after
      administration of the lowest possible doses. Various routes of application and
      target locations are currently being addressed in order to develop effective
      delivery systems for different targets and pathologies, including infectious
      pathologies, genetic pathologies and diseases associated with dysregulation of
      endogenous microRNAs. As with any new technology, several challenges and
      important aspects to be considered have risen on the road to clinical
      intervention, e.g. correct design of preclinical toxicology studies, regulatory
      concerns, and intellectual property protection. The main advantages related to
      the use of RNAi-based products in a clinical setting, and the latest clinical and
      preclinical studies using these compounds, are reviewed.

PMID- 19754221
TI  - Recombinant human thrombin: in surgical hemostasis.
AB  - Recombinant human thrombin (rhThrombin) is a serine protease coagulant,
      manufactured in vitro using recombinant DNA technology, which shares an identical
      amino acid sequence and similar structure with the native human protein. It is
      indicated for topical use as an aid to hemostasis in patients undergoing surgery.
      Topical rhThrombin 1000 U/mL was no less effective than bovine thrombin
      (bThrombin) 1000 U/mL as a hemostatic agent in a randomized, double-blind,
      multicenter, phase III trial in patients undergoing various surgical procedures
      (n = 401). Hemostasis, achieved within 10 minutes, occurred in 95.4% of
      rhThrombin versus 95.1% of bThrombin recipients (primary endpoint) in the overall
      surgical cohort. Moreover, hemostasis occurred rapidly, with more than 70% of
      recipients of rhThrombin or bThrombin achieving hemostasis within 3 minutes. In a
      post hoc, subgroup analysis of this phase III trial, rhThrombin was also
      effective in patients undergoing vascular surgery, with hemostasis occurring
      within 10 minutes at >90% of all vascular anastomotic sites. Significantly fewer
      patients undergoing various surgical procedures were seropositive for antibodies
      against rhThrombin than bThrombin 1 month after topical hemostatic treatment in
      the phase III trial. In a noncomparative, multicenter, phase IIIb trial (n =
      200), 1 month after vascular or spinal surgery where topical rhThrombin was used
      as a hemostat, the incidence of patients with evidence of anti-rhThrombin
      antibody formation was zero and did not differ between those classified as
      seropositive or seronegative for pre-existing anti-bThrombin antibodies at
      baseline (primary endpoint). rhThrombin was generally well tolerated during the
      treatment and 1-month follow-up periods in adult surgical patients, with a
      tolerability profile similar to that of bThrombin.

PMID- 19754222
TI  - Proteoglycan and collagen accumulation by passaged chondrocytes can be enhanced
      through side-by-side culture with primary chondrocytes.
AB  - Identifying a source of sufficient numbers of chondrocytes for cartilage tissue
      engineering is a major factor limiting its use clinically. Previously we
      demonstrated that combined coculture of passaged dedifferentiated articular
      chondrocytes with primary bovine chondrocytes will induce their
      redifferentiation. In this study we determine whether these two cell types have
      to be in contact, whether human chondrocytes respond similarly, and whether the
      ability of primary cells to influence passaged cells depends on the age of the
      donor. Coculture of primary and passaged bovine chondrocytes grown on filter
      inserts placed in the same culture well but not in direct contact resulted in the
      passaged cells accumulating matrix rich in proteoglycans and type II collagen.
      There was upregulation of type II collagen and Sox9 and decrease in type I
      collagen gene expression in the passaged cells, to levels not significantly
      different from those of primary chondrocytes. Passaged chondrocytes obtained from
      older animals responded similarly to cells from younger animals. Further,
      passaged human chondrocytes were also induced to form cartilage tissue when
      placed in side-by-side culture with bovine chondrocytes; these data suggest that
      a soluble factor(s) may be responsible for redifferentiation of passaged
      chondrocytes and that it is not species specific. The responsiveness of human
      chondrocytes to this factor(s) suggests that this approach may be suitable to
      overcome the problem of limited chondrocyte numbers for cartilage tissue
      engineering.

PMID- 19754223
TI  - Characteristic change and loss of in vivo osteogenic abilities of human bone
      marrow stromal cells during passage.
AB  - Although human bone marrow stromal cells (BMSCs) have the ability to form bone
      when transplanted, the responsible factors for in vivo osteogenic abilities are
      poorly understood. Here we report conditions that are required for human BMSCs to
      demonstrate their in vivo osteogenic abilities. BMSCs were obtained from healthy
      donors and their in vivo osteogenic abilities were analyzed. Transplantation
      analyses revealed that the passage number and length of osteogenic induction
      significantly affected ectopic bone formation. Although 2-week induction
      increased the percentage of success in bone formation compared with the 1-week
      induction, BMSCs completely lost their in vivo osteogenic ability after passage 4
      regardless of the length of osteogenic induction. Despite their in vivo
      osteogenic ability, no significant difference was observed in alkaline
      phosphatase activity or gene expression of osteogenic markers between BMSCs at
      passages 1 and 3. Differences were only observed in in vitro mineralizing
      abilities. Application of basic fibroblast growth factor helped to maintain the
      BMSCs in vivo osteogenic ability; basic fibroblast growth factor altered cell
      growth and expression of HLA-DR. The results strongly suggest that there are
      several required conditions for human BMSCs to demonstrate their bone-forming
      capabilities, which should be further investigated and considered when designing
      a protocol for clinical bone tissue engineering.

PMID- 19754224
TI  - Vascular endothelial growth factor inhibits bone morphogenetic protein 2
      expression in rat mesenchymal stem cells.
AB  - INTRODUCTION: While several studies report that bone morphogenetic proteins
      (BMPs) and vascular endothelial growth factor (VEGF) can act synergistically to
      improve bone tissue engineering, others suggest that VEGF inhibits osteogenesis.
      The purpose of these experiments was therefore to evaluate the effect of dual
      transfection of these growth factors and potential mechanisms of interaction on
      gene expression and osteogenesis in vitro and in vivo. METHODS: Marrow-derived
      mesenchymal stem cells (MSCs) were exposed to recombinant VEGF protein or
      transfected with adenoviruses encoding BMP2, VEGF, or LacZ in a variety of
      ratios. Alterations in gene and protein expression in vitro as well as bone
      formation in vivo were assessed. RESULTS: MSC exposure to AdV-VEGF or recombinant
      VEGF inhibited BMP2 mRNA expression, protein production, and MSC differentiation.
      Coculture experiments revealed that BMP2 suppression occurs through both an
      autocrine and a paracrine mechanism, occurring at the transcriptional level.
      Compared to controls, cotransfection of VEGF and BMP2 transgenes prevented
      ectopic bone formation in vivo. CONCLUSION: VEGF is a potent inhibitor of BMP2
      expression in MSCs, and supplementation or overexpression of VEGF inhibits
      osteogenesis in vitro and ectopic bone formation in vivo. Strategies to utilize
      MSCs in bone tissue engineering therefore require careful optimization and
      precise delivery of growth factors for maximal bone formation.

PMID- 19754229
TI  - Refugee research: strangers in a strange land.

PMID- 19754225
TI  - Shear stress induces nitric oxide-mediated vascular endothelial growth factor
      production in human adipose tissue mesenchymal stem cells.
AB  - It has been demonstrated that human adipose tissue-derived mesenchymal stem cells
      (hASCs) enhance vascular density in ischemic tissues, suggesting that they can
      differentiate into vascular cells or release angiogenic factors that may
      stimulate neoangiogenesis. Moreover, there is evidence that shear stress (SS) may
      activate proliferation and differentiation of embryonic and endothelial precursor
      stem cells into endothelial cells (ECs). In this work, we investigated the effect
      of laminar SS in promoting differentiation of hASCs into ECs. SS (10 dyn/cm(2) up
      to 96 h), produced by a cone plate system, failed to induce EC markers (CD31,
      vWF, Flk-1) on hASC assayed by RT-PCR and flow cytometry. In contrast, there was
      a cumulative production of nitric oxide (determined by Griess Reaction) and
      vascular endothelial growth factor (VEGF; by ELISA) up to 96 h of SS stimulation
      ( in nmol/10(4) cells: static: 0.20 +/- 0.03; SS: 1.78 +/- 0.38, n = 6; VEGF in
      pg/10(4) cells: static: 191.31 +/- v35.29; SS: 372.80 +/- 46.74, n = 6, P <
      0.05). Interestingly, the VEGF production was abrogated by 5 mM N(G)-L-nitro
      arginine methyl ester (L-NAME) treatment (VEGF in pg/10(4) cells: SS: 378.80 +/-
      46.74, n = 6; SS + L-NAME: 205.84 +/- 91.66, n = 4, P < 0.05). The results
      indicate that even though SS failed to induce EC surface markers in hASC under
      the tested conditions, it stimulated NO-dependent VEGF production.

PMID- 19754230
TI  - U.S. research universities' institutional conflict of interest policies.
AB  - RESEARCH UNIVERSITIES RECEIVE INCREASING amounts of income from intellectual
      property, which makes institutional conflict of interest (ICOI) policies
      increasingly important. We analyzed the content and scope of ICOI policies at 60
      research universities in the U.S. Association of American Universities. In
      particular, we focused on the following categories: disclosure, review,
      management, and prohibited or constrained activities. Most of the plans were
      relatively unelaborated, but 8 were elaborated "university as firm" policies that
      addressed the way officers and managers acting as agents for the university
      handled commercial activity through an array of management tools. However, even
      elaborated current ICOI policies may not be sufficient to manage ICOI because
      this type of commercial activity is not routine for universities in that faculty
      discovery or creation of intellectual property is not predictable. Thus, nearly
      all ICOI is managed on a case-by-case basis by various committees or senior
      institutional officials. As a result, institutional policy is only as strong as
      these committees and officers and the management plans they develop and monitor
      to handle conflicts.

PMID- 19754231
TI  - Challenges in measuring a new construct: perception of voluntariness for research
      and treatment decision making.
AB  - RELIABLE AND VALID MEASURES OF RELEVANT constructs are critical in the developing
      field of the empirical study of research ethics. The early phases of scale
      development for such constructs can be complex. We describe the methodological
      challenges of construct definition and operationalization and how we addressed
      them in our study to develop a measure of perception of voluntariness. We also
      briefly present our conceptual approach to the construct of voluntariness, which
      we defined as the perception of control over decision making. Our multifaceted
      approach to scale development ensured that we would develop a construct
      definition of sufficient breadth and depth, that our new measure of voluntariness
      would be applicable across disciplines, and that there was a clear link between
      our construct definition and items. The strategies discussed here can be adapted
      by other researchers who are considering a scale development study related to the
      empirical study of ethics.

PMID- 19754232
TI  - Privacy and confidentiality resources.
AB  - SEVERAL ORGANIZATIONS IN THE United States have a major interest in creating,
      testing, and using methods of data presentation that respect privacy and assure
      confidentiality. The following are among those that do so, and provide up-to-date
      information on these topics for the benefit of others who conduct human research:
      (1) The Committee on Privacy and Confidentiality of the American Statistical
      Association; (2) an interagency committee of the federal government, the Federal
      Committee on Statistical Methodology, and its subcommittees, the Confidentiality
      and Data Access Committee and the Committee on Privacy; (3) the Inter-university
      Consortium for Political and Social Research (University of Michigan), whose core
      mission is to archive important social science data, provide open and equitable
      access to data, and promote the effective use of data; and (4) Carnegie Mellon
      University's Department of Statistics, which has created an open-access online
      journal, the Journal on Privacy and Confidentiality. These resources are
      described, and URLs are provided to give readers web access to these resources.

PMID- 19754233
TI  - Introduction: all refugee research is not the same.

PMID- 19754234
TI  - Towards realizing the health-related millennium development goals for migrants
      from Burma in Thailand.
AB  - ETHICAL ISSUES IN HEALTH-RELATED research on politically oppressed migrant
      populations differ in significant ways from community health research in other
      contexts. The United Nations has set goals for such research. The health-related
      Millennium Development Goals (MDGs) were investigated in communities ("clusters")
      of migrants from Burma living in villages in the Sangkhlaburi District of
      Thailand, adjacent to the Thai-Burma border. Hunger was experienced regularly in
      70% of the households, and 26% of children under 5 years were underweight.
      Malaria, tuberculosis, and HIV/AIDS were prevalent. Few households took part in
      family planning, and there were many large families and disabled children. The
      health of the migrant populations was compromised by poverty, social exclusion,
      and under- or unemployment. Stakeholders in discussion groups concurred with the
      authors that tuberculosis detection and treatment and food production activities
      were important issues to address in developing projects to improve migrant
      health. This case study illustrates how the MDGs can be operationally defined.

PMID- 19754235
TI  - The control of foreigners as researchers in Thailand.
AB  - AN IMPORTANT ASPECT OF ETHICAL CONDUCT of field research is for the researcher to
      have an appropriate relationship with the legitimate gatekeepers of the field
      site. This paper describes our experiences of obtaining approval from regulatory
      authorities in Thailand for field research on Burmese migrants, and discusses the
      nature and rationale of such government control in Asia and Western countries. It
      is intended to guide future humanitarian researchers who are planning to study
      oppressed groups at politically sensitive research sites where regulatory
      authorities monitor both research sites and research performance. Thailand, like
      several other Southeast Asian countries, operates a permit system for foreign
      researchers. This permit system is designed to promote research activities in
      Thailand so that the results can be used to further the country's development,
      and to enhance the cooperation and collaboration between Thai and foreign
      researchers providing opportunities for the exchange of knowledge, technical
      expertise, and experience. This control of foreign researchers is not
      prohibitive; foreign humanitarian researchers can organize research and advance
      the welfare of targeted oppressed populations in cooperation with government
      agencies.

PMID- 19754236
TI  - Ethical and effective ethnographic research methods: a case study with afghan
      refugees in California.
AB  - SCHOLARLY STUDIES OF REFUGEES and other vulnerable populations carry special
      ethical concerns. In this invited case study of Afghan refugees in Fremont,
      California, I provide illustrations and recommendations of ethical research
      methods with refugees. I also compare and contrast some ethical issues in the
      U.S. with issues in Thailand. The qualitative, ethnographic methods I report here
      demonstrate how to conduct culturally sensitive investigations by ethically
      approaching gatekeepers and other community members to preserve autonomy, ensure
      confidentiality, build trust, and improve the accuracy of interpretations and
      results. Six groups at risk for being marginalized in multiple ways within
      refugee populations are described. Ten best practices are recommended for
      ethically acquiring an in-depth understanding of the refugees, their community,
      and appropriate research methods.

PMID- 19754237
TI  - Parents' online portrayals of pediatric treatment and research options.
AB  - PARENTS OF SERIOUSLY ILL CHILDREN FACE difficult decisions when standard
      therapies are limited or ineffective. In their search for information, they may
      turn to websites created by other parents facing similar experiences. We
      conducted a qualitative content analysis of 21 websites created by families with
      children affected by cancer or genetic disease, two serious conditions with a
      range of treatment and clinical trial options. Our research questions address how
      parent authors portray serious pediatric illness, available options, parties to
      decision making, and sources of influence. In addition, we examine what these
      sites reveal about family vulnerability to various risks, particularly the risk
      of misunderstanding the distinction between standard treatment and research and
      the risk of overestimating the likely benefits of research participation, as well
      as whether vulnerability varies by type of condition. Our results demonstrate
      typically favorable views on research, but with inadequate distinctions between
      research and treatment and a complex set of trade-offs in consideration of
      research risks and potential benefits. While portraits of vulnerability emerge
      for both parents and children, so do portraits of strength and resilience. As a
      result, parents describe frustration with both under- and overprotection from
      research participation. Our discussion of these findings clarifies the potential
      for parent-authored websites to inform and influence families considering
      research and treatment options for their seriously ill children.

PMID- 19754238
TI  - Benefits and burdens of participation in a longitudinal clinical trial.
AB  - SYSTEMATIC DATA ON THE IMPACT THAT longitudinal clinical trials have on patient
      participants are needed to ensure that all the risks and potential benefits of
      participating in clinical research are properly evaluated and disclosed.
      Recognizing the lack of systematic data on this topic, we surveyed 582
      individuals from Argentina, Brazil, and Thailand who were participating in the
      ESPRIT study, a Phase III randomized trial of interleukin-2 in HIV disease.
      Respondents were asked about the benefits and burdens of participating in ESPRIT
      using a self-administered survey. We found that 91% of respondents in the IL-2
      treatment arm and 79% in the no IL-2 control arm reported medical benefits from
      their participation. In addition, 68% in the IL-2 treatment arm and 60% of the no
      IL-2 controls reported non-medical benefits. Thirteen percent of the IL-2
      respondents and 5% of the non-IL2 respondents reported problems with their jobs
      due to study participation. Given that respondents, including those in the
      control arm, reported medical and non-medical benefits and burdens from their
      research participation, investigators and review committees should be aware of
      and respond to the potential for research participants to experience benefits and
      burdens that are unrelated to the intervention being tested.

PMID- 19754239
TI  - Prospective biorepository participants' perspectives on access to research
      results.
AB  - DISCLOSURE OF INDIVIDUAL RESEARCH results to research participants has been the
      subject of professional guidelines as well as scholarly commentary, yet
      controversy remains. To gather data on participant perspectives, we interviewed
      40 individuals from the Durham, North Carolina area about a biorepository consent
      form and conducted an in-depth analysis of responses to a series of questions
      concerning access to research results. Cross-cutting themes emerged about (1) the
      nature of research; (2) the nature of research results; (3) expectations
      concerning access to research results; and (4) practical issues in providing
      access to research results. Our findings highlight the importance for sound
      policy development of soliciting stakeholder input, and exploring the
      complexities behind their evaluations.

PMID- 19754243
TI  - Studies on the mechanism of printing film-coated tablets containing titanium
      dioxide in the film by using UV laser irradiation.
AB  - AIM: The purpose of this article is to study a detailed mechanism of printing
      when film-coated tablets were irradiated by UV laser at a wavelength of 355 nm.
      METHODS: Hydroxypropylmethylcellulose (HPMC) film containing titanium dioxide
      (TiO(2)) and the film not containing TiO(2) and TiO(2) powder were lirradiated by
      the UV laser and estimated by the morphological observation by zoom stereo
      microscope, thermogravimetric analysis (TGA), total color difference (dE), X-ray
      powder diffraction (XRD), and dispersive Raman microscopy. RESULTS: In the case
      of the film containing TiO(2), the film showed a visible change in its color from
      white to gray by the UV laser irradiation. By zoom stereo microscope, it was
      found that the entire UV laser-irradiated area was not grayed uniformly, but many
      black particles, whose diameter was about 2 microm, were observed on the film.
      When TiO(2) powder was irradiated by the UV laser, a visible change in its color
      from white to gray was observed similar to the case of the film containing
      TiO(2). There were many black particles locally in the UV laser-treated TiO(2)
      powder by the morphological observation, and these black particles, agglomerates
      of the grayed oxygen-defected TiO(2), were associated with the visible change of
      the TiO(2). CONCLUSION: It was found that the film-coated tablets were printed
      utilizing the formation of the black particles by the agglomeration of the grayed
      oxygen-defected TiO(2) by the UV laser irradiation.

PMID- 19754244
TI  - Pharmacokinetics of amitriptyline in rabbit skin and plasma following
      iontophoretic administrations.
AB  - BACKGROUND: Amitriptyline (AMT) is a tricyclic antidepressant with demonstrated
      local analgesic effects in human skin. AIM: We investigated the feasibility and
      mechanisms of iontophoretic delivery of AMT to rabbit dermis and plasma. METHOD:
      Two microdialysis probes were inserted into the upper dorsal shaved skin of
      tranquilized rabbits. After 1 hour, an iontophoresis cartridge was placed on top
      of one probe. The cartridge consisted of a stainless steel electrode covered with
      a pad that was filled with a 4.3 % AMT glycerin/water (50:50). Iontophoresis was
      performed at 100, 200, or 300 microA/cm(2) constant-current density for 60
      minutes. Dialysate samples were collected every 8 minutes for 3 hours and
      analyzed for AMT via a validated high-performance liquid chromatographic assay.
      Retrodialysis was performed at the other site. Blood samples were collected
      serially for 4 hours. RESULTS: In vivo retrodialysis recovery was 89 +/- 2%. AMT
      skin exposure increased non-proportionally with current density: AUCs were 19 +/-
      7, 119 +/- 56, and 615 +/- 302 mg/L/min for the 100, 200, and 300 muA/cm(2),
      respectively, and C(max) were 107 +/- 15, 1070 +/- 537, and 5870 +/- 1289
      microg/L. In vivo plasma concentrations were always below LLOQ (0.1 microg/mL).
      CONCLUSION: AMT can be administered by iontophoresis and produces significant
      skin concentrations and negligible plasma levels.

PMID- 19754245
TI  - Cellulolytic systems in insects.
AB  - Despite the presence of many carbohydrolytic activities in insects, their
      cellulolytic mechanisms are poorly understood. Whereas cellulase genes are absent
      from the genomes of Drosophila melanogaster or Bombyx mori, other insects such as
      termites produce their own cellulases. Recent studies using molecular biological
      techniques have brought new insights into the mechanisms by which the insects and
      their microbial symbionts digest cellulose in the small intestine. DNA sequences
      of cellulase and associated genes, as well as physiological and morphological
      information about the digestive systems of cellulase-producing insects, may allow
      the efficient use of cellulosic biomass as a sustainable energy source.

PMID- 19754246
TI  - Malaria management: past, present, and future.
AB  - The prospect of malaria eradication has been raised recently by the Bill and
      Melinda Gates Foundation with support from the international community. There are
      significant lessons to be learned from the major successes and failures of the
      eradication campaign of the 1960s, but cessation of transmission in the malaria
      heartlands of Africa will depend on a vaccine and better drugs and insecticides.
      Insect control is an essential part of reducing transmission. To date, two
      operational scale interventions, indoor residual spraying and deployment of long
      lasting insecticide-treated nets (LLINs), are effective at reducing transmission.
      Our ability to monitor and evaluate these interventions needs to be improved so
      that scarce resources can be sensibly deployed, and new interventions that reduce
      transmission in a cost-effective and efficient manner need to be developed. New
      interventions could include using transgenic mosquitoes, larviciding in urban
      areas, or utilizing cost-effective consumer products. Alongside this innovative
      development agenda, the potential negative impact of insecticide resistance,
      particularly on LLINs, for which only pyrethroids are available, needs to be
      monitored.

PMID- 19754247
TI  - Characteristics associated with mammography screening among both Hispanic and non
      Hispanic white women.
AB  - AIMS: This study explores whether certain population characteristics are
      associated with adherence to mammography screening guidelines among Hispanic and
      non-Hispanic white (NHW) women living in the southwestern United States. METHODS:
      Participants in a population-based study (4-Corners' Breast Cancer Study)
      included in this analysis were 790 Hispanic women and 1,441 NHW women.
      Multivariate logistic regression was used to compute the ethnic-specific adjusted
      odds ratios (OR) and 95% confidence intervals (CI) for the association of the
      outcome variable (adherent vs. nonadherent) and its correlates. Women were
      adherent if they had obtained their first mammogram between 41 and 50 years of
      age and had received at least one mammogram per 2 years or less. RESULTS: Ethnic
      specific associations were observed with certain population characteristics and
      mammography adherence. Specifically, characteristics that were significantly
      associated with adherence among Hispanic women were younger age (50-59 years),
      having a family history of breast cancer, nulliparity, hormone replacement
      therapy (HRT) use, nonsteroidal anti-inflammatory drug (NSAID) use, and
      performing regular breast self-examinations (BSE). Among NHW women, younger age
      (50-59 years), family history of breast cancer, obesity, consuming moderate
      amounts of alcohol, and taking HRT were associated with mammography adherence.
      When adjusting for the evaluated population characteristics, the relationship
      between ethnicity and mammography adherence was no longer apparent. CONCLUSIONS:
      Ethnic-specific characteristics appear to explain differences in mammography
      adherence among Hispanic and NHW women. Disparities in screening rates, late
      stage disease and breast cancer mortality that impact Hispanic women could
      potentially be addressed more effectively by interventions that specifically
      target the unique characteristics of the Hispanic population.

PMID- 19754248
TI  - Pattern of injury with a graded excitotoxic insult and ensuing chronic medial
      septal damage in the rat brain.
AB  - Brain damage caused by an acute injury depends on the initial severity of the
      injury and the time elapsed after the injury. To determine whether these two
      variables activate common mechanisms, we compared the response of the rat medial
      septum to insult with a graded series of concentrations of alpha-amino-3-hydroxy
      5-methyl-4-isoxazole propionic acid (AMPA) with the time-course effects of a low
      dose of AMPA. For this purpose we conducted a dose-response study at
      concentrations of AMPA between 0.27 and 10.8 nmol to measure atrophy of the
      septal area, losses of cholinergic and GABAergic neurons, astroglial and
      microglial reactions, and calcification. Cholinergic neurons, whose loss
      paralleled the degree of septal atrophy produced by AMPA, are more sensitive than
      GABAergic neurons to the injury produced by AMPA. At doses of AMPA above 2.7
      nmol, calcification and the degree of microglial reaction increased only in the
      GABAergic region of the septal area, whereas atrophy and neuronal loss reached a
      plateau. We chose the 2.7-nmol dose of AMPA to determine how these parameters
      were modified between 4 days and 6 months after injection. We found that atrophy
      and neuronal loss increased progressively through the 6-month study period,
      whereas astrogliosis ceased to be observed after 1 month, and calcium
      precipitates were never detected. We conclude that septal damage does not
      increase with the intensity of an excitotoxic insult. Rather, it progresses
      continuously after the insult. Because these two situations involve different
      mechanisms, short-term paradigms are inappropriate for interpreting the
      pathogenic mechanisms responsible for long-term neurodegenerative processes.

PMID- 19754249
TI  - Leakage pathway of different nano-restorative materials in class V cavities
      prepared by Er:YAG laser and bur preparation.
AB  - OBJECTIVE: The aim of this study was to evaluate the microleakage of different
      nano-restorative materials in Class V cavities prepared by Er:YAG laser and bur
      preparation. MATERIALS AND METHODS: Class V cavities were prepared on the buccal
      and lingual surfaces of 72 premolars by Er:YAG laser or bur. The occlusal margins
      were in enamel and the cervical margins were in cementum. Teeth were randomly
      assigned to six groups of 12 teeth (n = 24 cavities) each as follows: Group 1,
      Er:YAG laser preparation (E)+Ketac N100 (K); Group 2, bur preparation (B)+K;
      Group 3, E+Adper Prompt L-Pop (A)+Filtek Supreme XT Flow (FSF); Group 4, B+A+FSF;
      Group 5, E+A+Filtek Supreme XT (FS); Group 6, B+A+FS. All teeth were thermocycled
      500 times. Ten teeth from each group were chosen for the microleakage
      investigation and two teeth for the scanning electron microscope evaluation.
      Teeth prepared for the microleakage test were immersed in 0.5% basic fuchsin dye
      for 24 h. Afterwards, the teeth were sectioned and observed under a
      stereomicroscope for dye penetration. Data were analyzed by Kruskal-Wallis and
      Mann-Whitney U tests (p < 0.05). RESULTS: There were significant differences
      between occlusal and cervical regions for all groups (p < 0.05) except for Group
      1. Bur-prepared cavities showed less microleakage in all groups for enamel (p <
      0.05); however, in cementum there were no significant differences between the bur
      and laser-prepared cavities in nano-glass ionomer and flowable composite groups
      (p > 0.05). CONCLUSION: It may be concluded that the cavities prepared by Er:YAG
      laser showed higher degree of microleakage than those conventionally prepared by
      bur, regardless of the restorative material at enamel margins.

PMID- 19754250
TI  - Neural network analysis identifies scaffold properties necessary for in vitro
      chondrogenesis in elastin-like polypeptide biopolymer scaffolds.
AB  - The successful design of biomaterial scaffolds for articular cartilage tissue
      engineering requires an understanding of the impact of combinations of material
      formulation parameters on diverse and competing functional outcomes of
      biomaterial performance. This study sought to explore the use of a type of
      unsupervised artificial network, a self-organizing map, to identify relationships
      between scaffold formulation parameters (crosslink density, molecular weight, and
      concentration) and 11 such outcomes (including mechanical properties, matrix
      accumulation, metabolite usage and production, and histological appearance) for
      scaffolds formed from crosslinked elastin-like polypeptide (ELP) hydrogels. The
      artificial neural network recognized patterns in functional outcomes and provided
      a set of relationships between ELP formulation parameters and measured outcomes.
      Mapping resulted in the best mean separation amongst neurons for mechanical
      properties and pointed to crosslink density as the strongest predictor of most
      outcomes, followed by ELP concentration. The map also grouped formulations
      together that simultaneously resulted in the highest values for matrix
      production, greatest changes in metabolite consumption or production, and highest
      histological scores, indicating that the network was able to recognize patterns
      amongst diverse measurement outcomes. These results demonstrated the utility of
      artificial neural network tools for recognizing relationships in systems with
      competing parameters, toward the goal of optimizing and accelerating the design
      of biomaterial scaffolds for articular cartilage tissue engineering.

PMID- 19754259
TI  - The effect of low-level laser therapy on healing of skin incisions made using a
      diode laser in diabetic rats.
AB  - BACKGROUND AND OBJECTIVE: To investigate the effect of low-level laser therapy
      (LLLT) on healing of skin incisions made using a diode laser in diabetic rats.
      MATERIAL AND METHODS: Eighteen diabetic Wistar rats were used for this study. One
      incision was performed on the left side of the dorsum using a diode laser, and
      the other two incisions were made with a scalpel and diode laser on the right
      side of each rat. The wound on the left side of each rat received laser
      stimulation (10 J/cm(2)). The rats were assigned to three experimental groups.
      Group 1, scalpel (n = 18); Group 2, diode (n = 18); Group 3, diode +
      biostimulation (n = 18). RESULTS: Reepithelialization was fastest in Group 2 than
      Group 1 at day 10. The difference between Groups 1 and 3 was also statistically
      significant in reepithelialization at day 10. There was a significant difference
      between Groups 1 and 2 and between Groups 2 and 3 in inflammation at day 10.
      There was no difference between any of the groups in inflammation and
      reepithelialization at day 20. CONCLUSIONS: Scalpel incisions heal more slowly
      than diode and diode + biostimulation incisions in diabetic rats. We can suggest
      that diode + biostimulation may produce the least amount of tissue injury, with
      the fastest resolution of inflammatory response in diabetic rats. Diode laser
      incision (4 W) with 10-J/cm(2) LLLT seems to have a beneficial effect on skin
      incisions in diabetic rats.

PMID- 19754268
TI  - Endothelin-1 impairs nitric oxide signaling in endothelial cells through a
      protein kinase Cdelta-dependent activation of STAT3 and decreased endothelial
      nitric oxide synthase expression.
AB  - In an ovine model of persistent pulmonary hypertension of the newborn (PPHN),
      endothelin-1 (ET-1) expression is increased, while endothelial nitric oxide
      synthase (eNOS) expression is decreased. However, the molecular mechanisms by
      which ET-1 attenuates eNOS expression in endothelial cells are not completely
      understood. Thus, the goal of this study was to determine if the overexpression
      of ET-1 decreases eNOS expression in pulmonary arterial endothelial cells
      isolated from fetal lambs. To increase the ET-1 expression, cells were
      transfected with a plasmid coding for Prepro-ET-1, a precursor of ET-1. After
      overexpression of Prepro-ET-1, ET-1 levels in the culture medium were
      significantly increased (control = 805.3 +/- 69.8; Prepro-ET-1 overexpression =
      1351 +/- 127.9). eNOS promoter activity, protein levels, and NO generation were
      all significantly decreased by the overexpression of Prepro-ET-1. The decrease in
      transcription correlated with increased activity of protein kinase Cdelta
      (PKCdelta) and STAT3. Further, DNA binding activity of STAT3 was also increased
      by Prepro-ET-1 overexpression. The increase in STAT3 activity and decrease in
      eNOS promoter activity were inhibited by the overexpression of dominant negative
      mutants of PKCdelta or STAT3. Further, a 2 bp mutation in the STAT3 binding site
      in the eNOS promoter inhibited STAT3 binding and led to enhanced promoter
      activity in the presence of Prepro-ET-1 overexpression. In conclusion, ET-1
      secretion is increased by Prepro-ET-1 overexpression. This results in activation
      of PKCdelta, which phosphorylates STAT3, increasing its binding to the eNOS
      promoter. This in turn decreases eNOS promoter activity, protein levels, and NO
      production. Thus, ET-1 can reduce eNOS expression and NO generation in fetal
      pulmonary artery endothelial cells through PKCdelta-mediated activation of STAT3.

PMID- 19754267
TI  - Biophoton detection and low-intensity light therapy: a potential clinical
      partnership.
AB  - Low-intensity light therapy (LILT) is showing promise in the treatment of a wide
      variety of medical conditions. Concurrently, our knowledge of LILT mechanisms
      continues to expand. We are now aware of LILT's potential to induce cellular
      effects through, for example, accelerated ATP production and the mitigation of
      oxidative stress. In clinical use, however, it is often difficult to predict
      patient response to LILT. It appears that cellular reduction/oxidation (redox)
      state may play a central role in determining sensitivity to LILT and may help
      explain variability in patient responsiveness. In LILT, conditions associated
      with elevated reactive oxygen species (ROS) production, e.g. diabetic
      hyperglycemia, demonstrate increased sensitivity to LILT. Consequently,
      assessment of tissue redox conditions in vivo may prove helpful in identifying
      responsive tissues. A noninvasive redox measure may be useful in advancing
      investigation in LILT and may one day be helpful in better identifying responsive
      patients. The detection of biophotons, the production of which is associated with
      cellular redox state and the generation of ROS, represents just such an
      opportunity. In this review, we will present the case for pursuing further
      investigation into the potential clinical partnership between biophoton detection
      and LILT.

PMID- 19754269
TI  - Rapid construction of a plant RNA interference expression vector for hairpin RNA
      mediated targeting using a PCR-based method.
AB  - Here we describe a rapid and efficient PCR-mediated ligation protocol for
      constructing a plant RNA interference vector to express long hairpin RNA (hpRNA).
      In the protocol, four oligonucleotide primers were used and three rounds of PCRs
      performed. The product of the first PCR was used as a megaprimer for the second
      PCR to generate a chimeric molecule with a gene-specific sequence and a spacer
      spliced together. The chimeric product could be used as another megaprimer for
      the third PCR to ligate another gene-specific sequence to the other end of the
      spacer, but in the reverse orientation. Thus, within a few days, two gene
      specific sequences could be ligated to a spacer in the antisense and sense
      orientations using the PCR-mediated ligation method, without reliance on
      restriction cleavage and DNA ligation. The ligated product could be inserted into
      the plant expression vector for plant transformation. The transcribed RNA formed
      hpRNA constructs containing sense/antisense arms for specific gene targeting.
      Overexpression of hpRNA constructed by a Medicago truncatula xyloglucan
      endotransglycosylase gene retarded the growth of transgenic M. truncatula roots.

PMID- 19754270
TI  - Space of gene/species trees reconciliations and parsimonious models.
AB  - We describe algorithms to study the space of all possible reconciliations between
      a gene tree and a species tree, that is counting the size of this space,
      uniformly generate a random reconciliation, and exploring this space in optimal
      time using combinatorial operators. We also extend these algorithms for optimal
      and sub-optimal reconciliations according to the three usual combinatorial costs
      (duplication, loss, and mutation). Applying these algorithms to simulated and
      real gene family evolutionary scenarios, we observe that the LCA (Last Common
      Ancestor) based reconciliation is almost always identical to the real one.

PMID- 19754271
TI  - All human-specific gene losses are present in the genome as pseudogenes.
AB  - The loss of previously established genes has been proposed as a major force in
      evolutionary change. While genome sequencing of many new species offers the
      opportunity to identify cases of gene loss, it is unclear which algorithms offer
      the greatest accuracy or sensitivity. A number of methods to identify gene losses
      rely on the presence of a pseudogene for each loss. If genes are deleted when
      lost, however, such methods will fail to identify these cases. As the fate of
      gene losses is still unclear, we identified gene losses through a method that
      does not require pseudogenes to identify human-specific gene losses. Of the
      several hundred probable gene losses initially identified, we were unable to find
      a single case of unambiguous gene loss via deletion. We were also able to
      identify a large number of previously unannotated genes in the human genome, some
      of which also had evidence for transcription. Though our results suggest that
      pseudogene-based methods for finding gene losses in humans will not miss many
      events, we discuss the dependence of these conclusions on the divergence times
      among the species considered. Supplementary Material is provided (see online
      Supplementary Material at www.liebertonline.com ).

PMID- 19754272
TI  - Genetic map refinement using a comparative genomic approach.
AB  - Following various genetic mapping techniques conducted on different segregating
      populations, one or more genetic maps are obtained for a given species. However,
      recombination analyzes and other methods for gene mapping often fail to resolve
      the ordering of some pairs of neighboring markers, thereby leading to sets of
      markers ambiguously mapped to the same position. Each individual map is thus a
      partial order defined on the set of markers, and can be represented as a Directed
      Acyclic Graph (DAG). In this article, given a phylogenetic tree with a set of
      DAGs labeling each leaf (species), the goal is to infer, at each leaf, a single
      combined DAG that is as resolved as possible, considering the complementary
      information provided by individual maps, and the phylogenetic information
      provided by the species tree. After combining the individual maps of a leaf into
      a single DAG, we order incomparable markers by using two successive heuristics
      for minimizing two distances on the species tree: the breakpoint distance, and
      the Kemeny distance. We apply our algorithms to the plant species represented in
      the Gramene database, and we evaluate the simplified maps we obtained.

PMID- 19754273
TI  - Sorting cancer karyotypes by elementary operations.
AB  - Since the discovery of the "Philadelphia chromosome" in chronic myelogenous
      leukemia in 1960, there has been ongoing intensive research of chromosomal
      aberrations in cancer. These aberrations, which result in abnormally structured
      genomes, became a hallmark of cancer. Many studies provide evidence for the
      connection between chromosomal alterations and aberrant genes involved in the
      carcinogenesis process. An important problem in the analysis of cancer genomes is
      inferring the history of events leading to the observed aberrations. Cancer
      genomes are usually described in the form of karyotypes, which present the global
      changes in the genomes' structure. In this study, we propose a mathematical
      framework for analyzing chromosomal aberrations in cancer karyotypes. We
      introduce the problem of sorting karyotypes by elementary operations, which seeks
      a shortest sequence of elementary chromosomal events transforming a normal
      karyotype into a given (abnormal) cancerous karyotype. Under certain assumptions,
      we prove a lower bound for the elementary distance, and present a polynomial-time
      3-approximation algorithm for the problem. We applied our algorithm to karyotypes
      from the Mitelman database, which records cancer karyotypes reported in the
      scientific literature. Approximately 94% of the karyotypes in the database,
      totaling 58,464 karyotypes, supported our assumptions, and each of them was
      subjected to our algorithm. Remarkably, even though the algorithm is only
      guaranteed to generate a 3-approximation, it produced a sequence whose length
      matched the lower bound (and hence optimal) in 99.9% of the tested karyotypes.

PMID- 19754274
TI  - A whole genome study and identification of specific carcinogenic regions of the
      human papilloma viruses.
AB  - In this article, we undertake a study of the evolution of human papillomaviruses
      (HPV), whose potential to cause cervical cancer is well known. First, we found
      that the existing HPV groups are monophyletic and that the high risk of
      carcinogenicity taxa are usually clustered together. Then, we present a new
      algorithm for analyzing the information content of multiple sequence alignments
      in relation to epidemiologic carcinogenicity data to identify regions that would
      warrant additional experimental analyses. The new algorithm is based on a sliding
      window procedure and a p-value computation to identify genomic regions that are
      specific to HPVs causing disease. Examination of the genomes of 83 HPVs allowed
      us to identify specific regions that might be influenced by insertions, by
      deletions, or simply by mutations, and that may be of interest for further
      analyses. Supplementary Material is provided (see online Supplementary Material
      at www.libertonline.com ).

PMID- 19754275
TI  - RECOMB-Comparative Genomics Special Issue.

PMID- 19754280
TI  - A proposal for a thyroid imaging reporting and data system for ultrasound
      features of thyroid carcinoma.
AB  - BACKGROUND: Several thyroid ultrasound (TUS) findings have been associated with
      an increased risk for thyroid cancer; however, there is no consensus as to the
      format and style for reporting the results of TUS. The objective of this study
      was to discover the features indicative of malignancy in thyroid nodules based on
      TUS, generate an equation using these features that would be predictive of
      malignancy in thyroid nodules, and stratify the results of this equation into TUS
      categories reflecting the probability of malignancy. METHODS: We obtained odds
      ratios of TUS findings indicative of malignancy and probability of malignancy for
      each nodule as determined by logistic regression analysis of ultrasound (US)
      findings in 1694 patients who had US-guided fine-needle aspiration biopsy. We
      then generated an equation to predict the probability of malignancy based on TUS
      and developed categories ranging from lowest to highest probability of
      malignancy. We evaluated the reliability of this equation and the categories
      using cytology and histopathology information regarding malignancy in the thyroid
      nodules. RESULTS: We characterized 12 aspects of thyroid nodules as seen on TUS
      and developed an equation to predict P(us), the probability of a nodule being
      malignant based on these US findings. The equation was P(us) = 1/(1 + e(-z)),
      where e is the mathematical constant 2.71828 and z is the logit of malignant
      thyroid nodule. P(us) was stratified into five categories based on the
      probability of a nodule being malignant as indicated by the findings (TUS 1,
      benign; TUS 2, probably benign; TUS 3, indeterminate; TUS 4, probably malignant;
      TUS 5, malignant). There was a significant correlation between the cytological
      category and the TUS 1 through TUS 5 categories (r = 0.491, p < 0.001).
      CONCLUSIONS: We propose an equation to predict the probability of malignancy in
      thyroid nodules based on 12 features of thyroid nodules as noted on TUS. This
      equation, and the stratification of its results into categories, should be useful
      in reporting the findings of US for thyroid nodules and in guiding management
      decisions.

PMID- 19754304
TI  - Conformational mAb as a tool for integrin ligand discovery.
AB  - alpha(4)beta(1)-Integrin (very late antigen-4 (VLA-4)) mediates cell adhesion to
      cell surface ligands (VCAM-1). Binding of VLA-4 to VCAM-1 initiates rolling and
      firm adhesion of leukocytes to vascular endothelium followed by the extravasation
      into the tissue. VLA-4-dependent adhesion plays a key role in controlling
      leukocyte adhesive events. Small molecules that bind to the integrin ligand
      binding site and block its interaction with natural ligands represent promising
      candidates for treatment of several diseases. Following a flow cytometric screen
      for small molecule discovery, we took advantage of a conformationally sensitive
      anti-beta(1)-integrin antibody (HUTS-21) and a small LDV-containing ligand (LDV
      FITC) with known affinity to study binding affinities of several known and
      recently discovered integrin ligands. We found that binding of the LDV-containing
      small molecule induced exposure of HUTS-21 epitope and that the EC(50) for
      antibody binding was equal to previously reported K(d) for fluorescent LDV (LDV
      FITC). Thus, binding of HUTS-21 can be used to report ligand-binding site
      occupancy. We studied binding of two known integrin ligands (YLDV and TR14035),
      as well as of two novel compounds. EC(50) values for HUTS-21 binding showed good
      correlation with K(i)s determined in the competition assay with LDV-FITC for all
      ligands. A docking model suggests a common mode of binding for the small molecule
      VLA-4 ligands. This novel approach described here can be used to determine ligand
      binding affinities for unlabeled integrin ligands, and can be adapted to a high
      throughput screening format for identification of unknown integrin ligands.

PMID- 19754305
TI  - Prevalence of metabolic syndrome in the Mediterranean region of Turkey:
      evaluation of hypertension, diabetes mellitus, obesity, and dyslipidemia.
AB  - BACKGROUND: Metabolic syndrome has become a public health challenge worldwide.
      The aim of this study was to determine the prevalence of and risk factors for
      metabolic syndrome among adults in the Mediterranean region of Turkey. METHODS:
      This study included a total of 767 people from 20 to 83 years old from 4
      provinces calculated with respect to results of the 2000 census. People from the
      city centers, districts, and villages were selected by a stratified sampling
      method. Personal histories were recorded. Weight, height, and waist and hip
      circumferences were measured. Blood samples were obtained to determine glucose,
      total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density
      lipoprotein cholesterol (LDL-C), and triglycerides. Components of metabolic
      syndrome were modified from both Adult Treatment Panel III (ATP III) and
      International Diabetes Federation (IDF) criteria. RESULTS: The prevalence of
      metabolic syndrome was 34.6% (male, 31.2%; female, 37.3%) (P > 0.05) and 28.8%
      (male, 23.1%; female, 33.5% (P < 0.01) according to IDF criteria and ATP III,
      respectively. The highest prevalence of metabolic syndrome was present in
      subjects aged 60-69 years; in obese people (43.2%, P < 0.001); in Hatay province
      (36.5%, P < 0.001); and in districts (32.2%, P > 0.05). The prevalence of
      metabolic syndrome criteria in all 4 provinces was as follows: type 2 diabetes
      mellitus, 15%; hypertension, 41.4%; obesity, 44.1%; abdominal obesity, 56.8%; low
      HDL-C, 34.1%; hypertriglyceridemia, 35.9%; and high LDL-C, 27.4%. CONCLUSIONS:
      The high prevalence of metabolic syndrome in this region is an important public
      health problem that may cause an increase in mortality. Urgent preventive
      measurements should be implemented.

PMID- 19754306
TI  - Impaired interferon-gamma responses, increased interleukin-17 expression, and a
      tumor necrosis factor-alpha transcriptional program in invasive aspergillosis.
AB  - BACKGROUND: Invasive aspergillosis (IA) is the most common cause of death
      associated with fungal infection in the developed world. Historically,
      susceptibility to IA has been associated with prolonged neutropenia; however, IA
      has now become a major problem in patients on calcineurin inhibitors and
      allogenic hematopoietic stem cell transplant patients following engraftment.
      These observations suggest complex cellular mechanisms govern immunity to IA.
      METHODS: To characterize the key early events that govern outcome from infection
      with Aspergillus fumigatus, we performed a comparative immunochip microarray
      analysis of the pulmonary transcriptional response to IA between cyclophosphamide
      treated mice and immunocompetent mice at 24 h after infection. RESULTS: We
      demonstrate that death due to infection is associated with a failure to generate
      an incremental interferon-gamma response, increased levels of interleukin-5 and
      interleukin-17a transcript, coordinated expression of a network of tumor necrosis
      factor-alpha-related genes, and increased levels of tumor necrosis factor-alpha.
      In contrast, clearance of infection is associated with increased expression of a
      number genes encoding proteins involved in innate pathogen clearance, as well as
      apoptosis and control of inflammation. CONCLUSION: This first organ-level immune
      response transcriptional analysis for IA has enabled us to gain new insights into
      the mechanisms that govern fungal immunity in the lung.

PMID- 19754307
TI  - Dengue virus NS5 inhibits interferon-alpha signaling by blocking signal
      transducer and activator of transcription 2 phosphorylation.
AB  - Type I interferons (interferon [IFN]-alpha/beta) are key mediators of innate
      antiviral responses. Inhibition of IFN-mediated signal transduction by dengue
      viruses (DENVs), mosquito-borne flaviviruses of immense global health importance,
      probably plays a crucial role in determining the outcome of the virus-host
      interaction. Understanding the molecular basis of IFN antagonism by DENV would
      therefore provide critical insight into disease pathogenesis and new
      opportunities for development of antiviral therapies and rationally attenuated
      vaccines. Here we examine the effects of expression of DENV nonstructural
      proteins on cellular IFN responses. We show that expression of nonstructural
      protein 5 (NS5) alone inhibits IFN-alpha, but not IFN-gamma, signaling.
      Expression of the polymerase domain of NS5 is sufficient to inhibit IFN-alpha
      signaling. NS5 binds signal transducer and activator of transcription 2 (STAT2)
      and inhibits its phosphorylation. NS5 alone did not, however, induce degradation
      of STAT2, which occurs when all nonstructural proteins are expressed together. We
      conclude that DENV NS5 is a potent and specific type I IFN antagonist.

PMID- 19754308
TI  - BB0323 function is essential for Borrelia burgdorferi virulence and persistence
      through tick-rodent transmission cycle.
AB  - Borrelia burgdorferi bb0323 encodes an immunogenic protein in mammalian hosts,
      including humans. An analysis of bb0323 expression in vivo showed variable
      transcription throughout the spirochete infection cycle, with elevated expression
      during tick-mouse transmission. Deletion of bb0323 in infectious B. burgdorferi
      did not affect microbial survival in vitro, despite considerable alterations in
      growth kinetics and cell morphology. The bb0323 mutants were unable to infect
      either mice or ticks and were quickly eliminated from immunocompetent and
      immunodeficient hosts and the vector within the first few days after inoculation.
      Chromosomal complementation of the mutant with native bb0323 and phenotypic
      analysis in vivo indicated the substantial restoration of spirochete virulence
      and persistence throughout the mouse-tick infection cycle. The BB0323 protein may
      serve an indispensable physiological function that is more pronounced during
      microbial persistence and transitions between the host and the vector in vivo.
      Strategies to interfere with BB0323 function may interrupt the infectious cycle
      of spirochetes.

PMID- 19754310
TI  - Heritable factors play a major role in determining host responses to Wuchereria
      bancrofti infection in an isolated South Pacific island population.
AB  - BACKGROUND: It is increasingly recognized that host genetic factors may play an
      important role in determining the outcome of filarial infections. To test this
      hypothesis in bancroftian lymphatic filariasis, pedigree data were collected
      twice during an 18-year period from an isolated Polynesian population living on a
      Pacific island where lymphatic filariasis is endemic. METHODS: Using variance
      component analysis, we examined the contribution of shared genetic and
      environmental effects on host clinical and immune responses to filarial
      infection, along with potential confounding determinants. RESULTS: Sex was found
      to have a negligible influence on heritability estimates, but shared-household
      effects accounted for up to 32% of host variability. After accounting for these
      shared-household effects, heritability estimates suggested that levels of
      microfilariae and circulating adult worm antigen, as well as host eosinophil and
      immunoglobulin G antibody responses to larval and adult worm antigens, were
      highly heritable (range of heritability estimates, 0.15-0.84). CONCLUSIONS: These
      data provide evidence of a key role for genetic factors in determining the host
      response to filarial infections in humans and emphasize the complexity of the
      relationships among the host, parasite, and environment.

PMID- 19754309
TI  - Toll-like receptors 1 and 2 heterodimers alter Borrelia burgdorferi gene
      expression in mice and ticks.
AB  - Borrelia burgdorferi, the agent of Lyme disease, is recognized by Toll-like
      receptor (TLR) 1 and 2 heterodimers. Microarray analysis of in vivo B.
      burgdorferi gene expression in murine skin showed that several genes were altered
      in TLR1/2-deficient animals compared with wild-type mice. For example, expression
      of bbe21 (a gene involved in B. burgdorferi lp25 plasmid maintenance) and bb0665
      (a gene encoding a glycosyl transferase) were higher in TLR1/2-deficient mice
      than in control animals. In contrast, messenger RNA levels for bb0731 (a spoJ
      like gene) and bba74 (a gene encoding a periplasmic protein) were lower in TLR1/2
      deficient mice than in wild-type animals. The expression profiles of some of
      these genes were altered similarly in B. burgdorferi-infected ticks fed on
      control or TLR1/2-deficient mice. Quantitative reverse-transcription polymerase
      chain reaction analysis supported the microarray analysis and suggested that
      spirochete gene expression is altered by the milieu created by specific host
      TLRs, both in the murine host and in the arthropod vector.

PMID- 19754311
TI  - Genomewide association study of a rapid progression cohort identifies new
      susceptibility alleles for AIDS (ANRS Genomewide Association Study 03).
AB  - BACKGROUND: Previous genomewide association studies (GWASs) of AIDS have targeted
      end points based on the control of viral load and disease nonprogression. The
      discovery of genetic factors that predispose individuals to rapid progression to
      AIDS should also reveal new insights into the molecular etiology of the
      pathology. METHODS: We undertook a case-control GWAS of a unique cohort of 85
      human immunodeficiency virus type 1 (HIV-1)-infected patients who experienced
      rapid disease progression, using Illumina HumanHap300 BeadChips. The case group
      was compared with a control group of 1352 individuals for the 291,119 autosomal
      single-nucleotide polymorphisms (SNPs) passing the quality control tests, using
      the false-discovery rate (FDR) statistical method for multitest correction.
      RESULTS: Novel associations with rapid progression (FDR, < or = 25%) were
      identified for PRMT6 (P = 6.1 x 10(-7); odds ratio [OR], 0.24), SOX5 (P = 1.8 x
      10(-6); OR, 0.45), RXRG (P = 3.9 x 10(-6); OR, 3.29), and TGFBRAP1 (P = 7 x 10(
      6); OR, 0.34). The haplotype analysis identified exonic and promoter SNPs
      potentially important for PRMT6 and TGFBRAP1 function. CONCLUSIONS: The
      statistical and biological relevance of these associations and their high ORs
      underscore the power of extreme phenotypes for GWASs, even with a modest sample
      size. These genetic results emphasize the role of the transforming growth factor
      beta pathway in the pathogenesis of HIV-1 disease. Finally, the wealth of
      information provided by this study should help unravel new diagnostic and
      therapeutic targets.

PMID- 19754349
TI  - Therapeutic manipulation of the HIF hydroxylases.
AB  - The hypoxia-inducible factor (HIF) family of transcription factors is responsible
      for coordinating the cellular response to low oxygen levels in animals. By
      regulating the expression of a large array of target genes during hypoxia, these
      proteins also direct adaptive changes in the hematopoietic, cardiovascular, and
      respiratory systems. They also play roles in pathological processes, including
      tumorogenesis. In recent years, several oxygenases have been identified as key
      molecular oxygen sensors within the HIF system. The HIF hydroxylases regulate the
      stability and transcriptional activity of the HIF-alpha subunit by catalyzing
      hydroxylation of specific proline and asparaginyl residues, respectively. They
      require oxygen and 2-oxoglutarate (2OG) as co-substrates, and depend upon non
      heme ferrous iron (Fe(II)) as a cofactor. This article summarizes current
      understanding of the biochemistry of the HIF hydroxylases, identifies targets for
      their pharmacological manipulation, and discusses their potential in the
      therapeutic manipulation of the HIF system.

PMID- 19754350
TI  - Haplotypes of microsomal epoxide hydrolase and x-ray cross-complementing group 1
      genes in Indian hepatocellular carcinoma patients.
AB  - Hepatocellular carcinoma (HCC) is a life-threatening disease that is often
      associated with chronic infection by hepatitis B and C viruses. Genetic
      polymorphisms have been reported to alter the risk for HCC development. Genetic
      studies based on the haplotype have an increased power for detecting disease
      associations compared with single-nucleotide polymorphism-based analysis. There
      is sufficient epidemiological evidence suggesting a link between genetic
      polymorphism and haplotypes of microsomal epoxide hydrolase (mEPHX) and X-ray
      cross-complementing group 1 (XRCC1) with altered cancer risk. However, no report
      correlates the risk of HCC development with mEPHX and XRCC1 haplotypes. Genetic
      polymorphism of these genes was studied for haplotype construction in 169 control
      subjects, 174 hepatitis patients, and 63 HCC patients. 113Tyr-139Arg and 113His
      139His haplotypes of mEPHX significantly elevated the risk for HCC by 1.4- and
      1.5-folds, respectively. Arg-His-Arg haplotype of XRCC1 significantly enhanced
      the risk for hepatitis by 2.8-folds (p = 0.001), but not for HCC (odds ratio =
      1.5; p = 0.28). mEPHX haplotypes shared a positive association with HCC risk in
      India.

PMID- 19754353
TI  - Genetic and biochemical heterogeneity of cardiac troponins: clinical and
      laboratory implications.
AB  - The contractile sarcomeric pool of skeletal muscle and heart consists of a highly
      ordered arrangement of actin thin filaments, tropomyosin and proteins of the
      troponin complex: troponin I (TnI), troponin T (TnT) and troponin C (TnC). The
      cardiac myocyte expresses specific isoforms of both TnI and TnT (cTnI and cTnT,
      respectively), which can be distinguished from skeletal muscle isoforms by rapid
      and reliable immunoassays. Due to their superior cardiac specificity, cTnI and
      cTnT have become the recommended biomarkers for the diagnosis of myocardial
      injury. The most common applications are for risk stratification and diagnosis of
      acute coronary syndromes, albeit they can also be used for assessing a variety of
      other myocardial disorders. However, the excellent diagnostic efficiency of
      cardiac troponin testing is jeopardized by some pre-analytical issues (unsuitable
      specimens for testing, analyte stability, handling, transportation and storage of
      specimens prior to analysis), as well as by analytical concerns related to
      standardization or harmonization of cTnI immunoassays, imprecision at low
      concentrations, antibody specificity, immunoreactivity of plasma isoforms
      released in the blood after myocardial injury, interference from autoantibodies,
      heterophilic antibodies, rheumatoid factor, and human anti-mouse antibodies. In
      addition, although the influence of some known mutations in cTnT and cTnI on
      calcium sensitivity and force generation have been readily demonstrated, their
      influence on current immunoassays is unknown. Most mutations in these proteins
      may contribute to the development of certain cardiomyopathies, namely
      hypertrophic and restrictive. In these situations, the phenotype is characterized
      by the underlying diseases, and the ability to detect cTnT or cTnI is of
      relatively little clinical significance. However, the cTnT Arg129Lys polymorphism
      and those observed in the stable domain of cTnI do not significantly alter the
      functional properties of the molecule within the myocardium and thus are
      predictably asymptomatic. While the actual prevalence of these polymorphisms in
      the general population is still unknown, they might be a source of potential
      analytical problems; modifying the immunogenicity of the molecule and leading to
      potential false negative results. The goal of this article is to provide an
      overview on the potential technical and analytical challenges in the measurement
      of cardiac troponins, along with the significance of polymorphisms in the genes
      encoding for cTnI and cTnT in both health and disease.

PMID- 19754354
TI  - Egyptian glycogen storage disease type III - identification of six novel AGL
      mutations, including a large 1.5 kb deletion and a missense mutation p.L620P with
      subtype IIId.
AB  - BACKGROUND: Glycogen storage disease type III (GSD III) is caused by mutations in
      AGL which encodes for a single protein with two enzyme activities: oligo-1, 4-1,
      4-glucantransferase (transferase) and amylo-1, 6-glucosidase. Activity of both
      enzymes is lost in most patients with GSD III, but in the very rare subtype IIId,
      transferase activity is deficient. Since the spectrum of AGL mutations is
      dependent on the ethnic group, we investigated the clinical and molecular
      characteristics in Egyptian patients with GSD III. METHODS: Clinical features
      were examined in five Egyptian patients. AGL was sequenced and AGL haplotypes
      were determined. RESULTS: Six novel AGL mutations were identified: a large
      deletion (c.3481-3588+1417del1525 bp), two insertions (c.1389insG and
      c.2368insA), two small deletions (c.2223-2224delGT and c.4041delT), and a
      missense mutation (p.L620P). p.L620P was found in a patient with IIId. Each
      mutation was located on a different AGL haplotype. CONCLUSIONS: Our results
      suggest that there is allelic and phenotypic heterogeneity of GSD III in Egypt.
      This is the second description of a large deletion in AGL. p.L620P is the second
      mutation found in GSD IIId.

PMID- 19754355
TI  - Molecular features, markers, drug targets, and prospective targeted therapeutics
      in cardiac myxoma.
AB  - Treatment of sporadic cardiac myxoma (CM) has always been a challenging task.
      Currently, surgical excision remains the only option; however, targeted drug
      discovery schemes are in progress in order to improve treatment strategies and
      efficacy. The molecular mechanisms behind CM pathogenesis are still not totally
      unveiled thus drug target identification is still at early steps, trying to
      compile structured data on the pathophysiology of CM, targets and targeting
      moieties. Five critical disease pathways involving molecules of seven functional
      groups have been recently shown by us to be associated with the pathogenesis of
      CM. In addition, 15 to 20 drug targets and their targeting molecules have also
      mapped on pathways in an effort to start decoding the molecular profiles based on
      which early efforts for CM patient stratification into targeted therapeutic
      regimes. The present review describes the current data and discusses critical
      issues in the field of targeted and personalized medicine of CM.

PMID- 19754356
TI  - Caspase-independent pathways of programmed cell death: the unraveling of new
      targets of cancer therapy?
AB  - In the past few years, accumulating evidence in the literature supports the
      existence of pathways of caspase-independent programmed cell death (CI-PCD).
      These pathways are likely to be acting as 'death backup systems' that ensure
      effective removal of defective cells from the organism. Similar to classical
      apoptosis i.e. caspase-dependent programmed cell death (CD-PCD), the
      mitochondrion is the main organelle orchestrating the series of events which are
      required for the induction of CI-PCD. In addition, the pro-apoptotic proteins Bax
      and Bid are also key participants in CI-PCD. However, contrary to CD-PCD, CI-PCD
      involves executioners other than the caspases which include the cathepsins, the
      calpains and serine proteases. The protein AIF may also play an important role in
      the induction of CI-PCD. In this review we report current knowledge on CI-PCD and
      provide evidence for its regulation by chemotherapeutic agents currently used in
      the clinic and under investigation in clinical trials. Lastly, we discuss how the
      study of natural and synthetic agents triggering CI-PCD may help in the
      pharmacological design of a new generation of more effective chemotherapeutic
      drugs. The use of such drugs activating both CD-PCD and CI-PCD pathways should
      achieve a more successful eradication of carcinogenic cells and the attainment of
      lower levels of tumor resistance.

PMID- 19754357
TI  - The PI3K/Akt/mTOR pathway as therapeutic target in neuroblastoma.
AB  - The phosphatidylinositol 3'-kinase (PI3K)/Akt/mammalian target of rapamycin
      (mTOR) pathway is one of the most potent prosurvival signaling cascades that is
      aberrantly activated in a variety of human cancers. Recent evidence demonstrates
      that pathological activation of Akt also frequently occurs in neuroblastoma and
      correlates with poor prognosis. Thus, therapeutic targeting of PI3K/Akt/mTOR may
      present a promising approach for the design of molecular targeted therapies in
      neuroblastoma. Several strategies have in recent years been developed to
      interfere with distinct components of PI3K/Akt/mTOR signaling at different levels
      of the cascade. It will be subject to future studies to evaluate which of these
      compounds are most suitable for the treatment of neuroblastoma. Eventually,
      PI3K/Akt/mTOR targeting agents may open novel perspectives to improve the poor
      prognosis of patients with neuroblastoma especially in advanced stages of the
      disease.

PMID- 19754358
TI  - Sunitinib (SUTENT, SU11248) suppresses tumor growth and induces apoptosis in
      xenograft models of human hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the fifth most common and third deadliest
      primary neoplasm. Since HCC is a particularly vascular solid tumor, we determined
      the antitumor and antiangiogenic activities of sunitinib malate, a potent
      inhibitor of two receptors involved in angiogenesis - vascular endothelial growth
      factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR). In
      the present study, we reported that treatment of HepG2 and SK-Hep-1 cells with
      sunitinib led to growth inhibition and apoptosis in a dose-dependent fashion.
      Sunitinib inhibited phosphorylation of VEGFR-2 at Tyr951 and PDGFR-beta at
      Tyr1021 both in vitro and in vivo. Sunitinib also suppressed tumor growth of five
      patient-derived xenografts. Sunitinib-induced tumor growth inhibition was
      associated with increased apoptosis, reduced microvessel density and inhibition
      of cell proliferation. This study provides a strong rationale for further
      clinical investigation of sunitinib in patients with hepatocellular carcinoma.

PMID- 19754359
TI  - Crosstalk between epidermal growth factor receptor- and insulin-like growth
      factor-1 receptor signaling: implications for cancer therapy.
AB  - Both the epidermal growth factor receptor (EGFR) and the insulin-like growth
      factor-1 receptor (IGF-1R) can contribute to tumor development and -progression
      through their effects on cell proliferation, inhibition of apoptosis,
      angiogenesis, anchorage-independent growth and tumor-associated inflammation.
      EGFR-targeting monoclonal antibodies and small molecule tyrosine kinase
      inhibitors are currently in clinical use for the treatment of several types of
      cancer. However, primary and acquired resistance to these agents often occurs and
      thereby limits the clinical efficacy of mono-specific targeted therapy. Results
      from both in vitro and in vivo studies indicate that cross-talk between EGFR and
      IGF-1R can lead to acquired resistance against EGFR-targeted drugs. This review
      describes the interface between the EGFR and IGF-1R signaling networks and the
      implications of the extensive cross-talk between these two receptor systems for
      cancer therapy. EGFR and IGF-1R interact on multiple levels, either through a
      direct association between the two receptors, by mediating the availability of
      each others ligands, or indirectly, via common interaction partners such as G
      protein coupled receptors (GPCR) or downstream signaling molecules. This multi
      layered cross-talk and its involvement in the induction of resistance to targeted
      therapies provide a clear rationale for dual targeting of EGFR and IGF-1R. We
      discuss several (potential) strategies to simultaneously inhibit EGFR and IGF-1R
      signaling as promising novel therapeutic approaches.

PMID- 19754360
TI  - Heat shock protein 90 - a potential target in the treatment of human acute
      myelogenous leukemia.
AB  - Heat shock proteins (HSPs) are molecular chaperones that stabilize folding and
      conformation of normal as well as oncogenic proteins. These chaperones thereby
      prevent the formation of protein aggregates. HSPs are often overexpressed in
      human malignancies, including AML. HSP90 is the main chaperon required for the
      stabilization of multiple oncogenic kinases involved in the development of acute
      myelogenous leukemia (AML). HSP90 client proteins are involved in the regulation
      of apoptosis, proliferation, autophagy and cell cycle progression; several of
      these proteins are in addition considered as possible therapeutic targets for the
      treatment of AML. HSP90 inhibition thereby offers the possibility to modulate
      several intracellular regulatory pathways through targeting of a single molecule.
      Several direct inhibitors of HSP90 have been developed, and they are classified
      into four groups: benzoquinon ansamycines and their derivatives, radicicol and
      its derivates, small synthetic inhibitors and a final group of other inhibitors.
      The HSP90 activity is regulated by posttranscriptional modulation; HSP90
      inhibition can thereby be indirectly achieved through increased acetylation
      caused by histone deacetylase inhibitors. Many of these agents have entered phase
      I/II clinical trials, and the results from these initial studies have documented
      that HSP90 inhibition can mediate antileukemic effects in vivo. However, one
      would expect immunosuppressive side effects because HSP90 inhibitors have both
      direct and indirect inhibitory effects on T cell activation. Thus, future
      clinical studies are needed to clarify the efficiency and toxicity of HSP90
      inhibitors in the treatment of human AML, including studies where HSP90
      inhibitors are combined with conventional chemotherapy.

PMID- 19754361
TI  - Increased tumor oxygenation and drug uptake during anti-angiogenic weekly low
      dose cyclophosphamide enhances the anti-tumor effect of weekly tirapazamine.
AB  - Metronomic cyclophosphamide treatment is associated with anti-angiogenic activity
      and is anticipated to generate exploitable hypoxia using hypoxia-activated
      prodrugs. Weekly administration of tirapazamine (TPZ; 5 mg/kg body weight i.p.)
      failed to inhibit the growth of 9L gliosarcoma tumors grown s.c. in scid mice.
      However, the anti-tumor effect of weekly cyclophosphamide (CPA) treatment (140
      mg/kg BW i.p.) was substantially enhanced by weekly TPZ administration. An
      extended tumor free period and increased frequency of tumor eradication without
      overt toxicity were observed when TPZ was given 3, 4 or 5 days after each weekly
      CPA treatment. Following the 2(nd) CPA injection, Electron Paramagnetic Resonance
      (EPR) Oximetry indicated significant increases in tumor pO(2), starting at 48 hr,
      which further increased after the 3(rd) CPA injection. pO(2) levels were,
      however, stable in growing untreated tumors. A strong negative correlation (
      0.81) between tumor pO(2) and tumor volume during 21 days of weekly CPA
      chemotherapy was observed, indicating increasing tumor pO(2) with decreasing
      tumor volume. Furthermore, CPA treatment resulted in increased tumor uptake of
      activated CPA. CPA induced increases in VEGF RNA, which reached a maximum on day
      1, and in PLGF RNA which was sustained throughout the treatment, while anti
      angiogenic host thrombospondin-1 increased dramatically through day 7 post-CPA
      treatment. Weekly cyclophosphamide treatment was anticipated to generate
      exploitable hypoxia. However, our findings suggest that weekly CPA treatment
      induces a functional improvement of tumor vasculature, which is characterized by
      increased tumor oxygenation and drug uptake in tumors, thus counter-intuitively,
      benefiting intratumoral activation of TPZ and perhaps other bioreductive drugs.

PMID- 19754362
TI  - In vivo study on vertical transmission of the HIV-1 gag gene via mouse oocytes.
AB  - Acquired immunodeficiency syndrome (AIDS) is a major public health problem
      worldwide. This study was performed to explore the feasibility of vertical
      transmission of human immunodeficiency virus-1 (HIV-1) gag gene via oocyte. The
      recombinant plasmid (pIRES2-EGFP-gag) was injected into mouse ovaries to
      transfect germ cells. Induction of superovulation and then animal mating were
      performed to collect oocytes and two-cell embryos. Positive FISH signals for HIV
      1 gag DNA were detected in the nuclei of oocytes and embryos, and in chromosomes
      of mature oocytes, indicated integration of the gene into the oocyte genome and
      gene replication in the embryo. HIV-1 gag cDNA positive bands detected by RT-PCR
      in oocytes and embryos indicated successful gene transcription, while positive
      immunofluorescence signals for HIV-1 gag protein indicated successful translation
      in both oocytes and embryos. The HIV-1 gag gene was transmitted vertically to the
      next generation via oocytes and it retained its function in replication,
      transcription and translation following at least one mitotic division in embryos.

PMID- 19754363
TI  - Bilirubin induced neurological damage: from the cell to the newborn.

PMID- 19754364
TI  - Bilirubin chemistry and metabolism; harmful and protective aspects.
AB  - Unconjugated bilirubin (UCB), the principal mammalian bile pigment, is the end
      product of heme catabolism. Both belong to the superfamily of tetrapyrrolic
      compounds that serve multiple biological functions in animals and plants. Its six
      internal hydrogen bonds give UCB a unique structure responsible for its physico
      chemical properties and biological effects. Like many weakly-polar, poorly
      soluble compounds, UCB is transported in blood tightly bound to albumin, with
      less than 0.01% of total bilirubin circulating in an unbound form (free
      bilirubin, Bf). This fraction governs the diffusion of UCB into tissues, and
      therefore Bf is responsible for both its beneficial and toxic effects on cells.
      Although, UCB was long thought to be a non-functional waste product, recent
      studies have shown that the antioxidant effects of mildly elevated serum
      bilirubin levels, as well as activation of heme oxygenase, may protect against
      diseases associated with oxidative stress, such as atherosclerosis. By contrast,
      markedly elevated serum UCB levels may cause severe neurological damage,
      especially in neonates. The regulation of cellular UCB content, by its
      conjugation, oxidation, and export, are, therefore of paramount importance to
      cellular health.

PMID- 19754365
TI  - The role of ABC transporters in protecting cells from bilirubin toxicity.
AB  - The ATP-binding cassette (ABC) superfamily is the largest transporter family
      known to translocate a wide variety of exogenous and endogenous substrates across
      cell membranes. In this chapter we review the potential role of three ABC
      proteins in the transport of unconjugated bilirubin (UCB). These transporters are
      MRP1, MRP3 and PGP (MDR1). MRP1 is expressed at high levels in most epithelia,
      usually at the basolateral membrane. Among a multiplicity of substrates, MRP1
      mediates the ATP-dependent cellular export of UCB, and its role has been
      demonstrated in protecting cells from UCB toxicity. MRP3 is an organic anion
      transporter whose major substrates are GSH conjugates of organic compounds. Among
      the MRP family members, MRP3 shares the highest degree of amino acid homology
      with MRP1. Although the hepatic expression of MRP3 has been reported to be up
      regulated by bilirubin and bilirubin glucuronides, it is unknown whether MRP3 is
      also involved in the transport of UCB. PGP is expressed in organs involved in the
      elimination of endo- and xenobiotics and UCB is one of these substrates. Since
      the Km of PGP for UCB is well above pathophysiological levels of Bf, it remains
      uncertain whether it has a role in protecting against UCB cytotoxicity.

PMID- 19754366
TI  - Blood-brain interfaces and bilirubin-induced neurological diseases.
AB  - The endothelium of the brain microvessels and the choroid plexus epithelium form
      highly specialized cellular barriers referred to as blood-brain interfaces
      through which molecular exchanges take place between the blood and the neuropil
      or the cerebrospinal fluid, respectively. Within the brain, the ependyma and the
      pia-glia limitans modulate exchanges between the neuropil and the cerebrospinal
      fluid. All these interfaces are key elements of neuroprotection and fulfill
      trophic functions; both properties are critical to harmonious brain development
      and maturation. By analogy to hepatic bilirubin detoxification pathways, we
      review the transport and metabolic mechanisms which in all these interfaces may
      participate in the regulation of bilirubin cerebral bioavailability in
      physiologic conditions, both in adult and in developing brain. We specifically
      address the role of ABC and OATP transporters, glutathione-S-transferases, and
      the potential involvement of glucuronoconjugation and oxidative metabolic
      pathways. Regulatory mechanisms are explored which are involved in the induction
      of these pathways and represent potential pharmacological targets to prevent
      bilirubin accumulation into the brain. We then review the possible alteration of
      the neuroprotective and trophic barrier functions in the course of bilirubin
      induced neurological dysfunctions resulting from hyperbilirubinemia. Finally, we
      highlight the role of the blood-brain and blood-CSF barriers in regulating the
      brain biodisposition of candidate drugs for the treatment or prevention of
      bilirubin-induced brain injury.

PMID- 19754367
TI  - Redox state, oxidative stress, and molecular mechanisms of protective and toxic
      effects of bilirubin on cells.
AB  - Unconjugated bilirubin (UCB) is the major degradation product of the heme
      catabolism. UCB is a potent antioxidant molecule as well as an indirect pro
      oxidant generator. Growing evidence suggests that its major cellular effects are
      mediated by inhibiting proliferation in cancer cell lines and eliciting
      cytotoxicity, particularly in neurons and glial cells. Here we describe studies
      showing that alteration of the redox status and generation of oxidative stress
      are likely early events responsible for UCB-induced cytotoxicity. We then
      elucidate some of the molecular pathways that govern these effects.

PMID- 19754368
TI  - Contribution of inflammatory processes to nerve cell toxicity by bilirubin and
      efficacy of potential therapeutic agents.
AB  - Hyperbilirubinemia is a common condition in neonatal life, where elevated levels
      of unconjugated bilirubin (UCB) may lead to adverse neurologic outcomes, namely
      in the presence of inflammatory features. In this review, we summarize recent
      concepts on UCB damage to brain cells and associated neuroinflammation research.
      Exposure of astrocytes and microglia to UCB initiates an inflammatory response
      with the release of proinflammatory cytokines, such as TNF-alpha, IL-1beta and IL
      6, accumulation of extracellular glutamate and a time-dependent cell death.
      Moreover, undifferentiated cells revealed to be particularly susceptible to UCB
      induced immunostimulation pointing to a mechanism that may preside to the
      vulnerability evidenced by premature newborns. Evaluation of intracellular
      mechanisms of astrocyte and microglia to UCB revealed that TNF-alpha and IL-1beta
      pathways as well as MAPK and NF-kappaB signaling cascades are key mediators of
      both cytokine production and cell toxicity observed upon UCB challenge.
      Understanding these mechanisms is essential for the development of new strategies
      targeting UCB-induced neurotoxicity. Thus, a therapeutic approach for the
      prevention or amelioration of neurological deficits resulting from moderate to
      severe hyperbilirubinemia, may consist on the use of immunomodulators, such as IL
      10 that showed ability to suppress the release of cytokines from astrocytes
      exposed to UCB, glycoursodeoxycholic acid (GUDCA) that abrogated both UCB
      stimulated cytokine secretion and UCB-induced loss of cell survival, and
      minocycline that evidenced a unique role in preventing neurodegeneration in in
      vitro and in vivo models. Novel pharmacological strategies may reduce the
      incidence of UCB encephalopathy and prevent minor cerebral lesions that may
      result in mental illness.

PMID- 19754369
TI  - Pharmacological therapies for unconjugated hyperbilirubinemia.
AB  - Severe unconjugated hyperbilirubinemia, seen mainly in neonates, may cause
      kernicterus and death. Conventional treatment for severe unconjugated
      hyperbilirubinemia consists of phototherapy and exchange transfusion.
      Phototherapy, however, has several known disadvantages while exchange transfusion
      is associated with a significant morbidity, and even mortality. These harmful
      effects indicate the need to develop alternative pharmacological treatment
      strategies for unconjugated hyperbilirubinemia. Generally, these strategies aim
      to decrease the plasma concentration of unconjugated bilirubin (UCB) by
      inhibiting production, stimulating hepatic clearance, or interrupting the
      enterohepatic circulation of the pigment. To be considered for routine clinical
      use, an alternative treatment strategy should be less invasive and at least as
      effective and safe as phototherapy. Several pharmacological therapies such as
      metalloporhyrins, clofibrate, bile salts, laxatives and bilirubin oxidase may
      meet these criteria in the future, but none of them has yet been evaluated
      sufficiently to allow routine application. This review aims to discuss the state
      of the art and future perspectives in pharmacological treatment of neonatal
      jaundice.

PMID- 19754370
TI  - Intervention guidelines for neonatal hyperbilirubinemia: an evidence based
      quagmire.
AB  - The American Academy of Pediatrics has proposed guidelines for treating term/near
      term infants with hyperbilirubinemia based primarily on maintaining the total
      serum bilirubin concentration (TSB) below a "critical" level of 25 mg/dL (426
      micromol/L). We estimated the sensitivity and specificity of this critical TSB
      using patient data from published reports. A TSB >25 mg/dL is recorded in about
      92% of term/near term infants with kernicterus. When TSB is adjusted lower for
      risk factors of prematurity, sepsis, and isoimmune hemolytic disease, the
      guidelines have nearly a 98% sensitivity. The specificity of the critical TSB,
      however, is very poor; false positive rates exceed 90% if all cases of acute
      bilirubin toxicity are included, and about 94-96% if the endpoint is mild or
      severe residual brain injury. Clinically measurable confounders that might
      explain the large variance in critical TSB include the plasma unbound "free"
      bilirubin concentration (Bf) and, possibly, the concentration of bilirubin
      photoisomers. Limited clinical experience supports the proposition that Bf is
      superior to TSB in identifying patients at risk. Specificity of Bf and TSB was
      compared in small cohort of babies with acute and permanent bilirubin
      encephalopathy. The false positive rate for TSB (at 100% sensitivity) was 94%,
      compared with only 55% for Bf. A more comprehensive comparison of TSB and Bf,
      controlled for clinical confounders and photoiomers, is needed to formulate
      intervention guidelines with improved specificity that will reduce hospital
      admissions for unnecessary treatment.

PMID- 19754371
TI  - Polysulfated/sulfonated compounds for the development of drugs at the crossroad
      of viral infection and oncogenesis.
AB  - Virus infection and oncogenesis are two tightly linked processes. Some viruses
      are endowed with a direct transforming capability and infection activates
      inflammation that, in turn, favours tumor progression. Also, both inflammation
      and tumor trigger (and are strongly dependent from) angiogenesis. Finally, some
      oncogenic viruses release "virokines" that contribute to the development of virus
      associated tumors. At a molecular level, viral proteins, cytokines, receptors and
      adhesion molecules "cross-contribute" to the different processes and, amazingly,
      many of them bind to heparin and to heparan sulfate proteoglycans to exert their
      functions. Heparin-like polysulfated (PS) or polysulfonated (PSN) compounds are
      an heterogeneous group of natural or synthetic molecules whose prototypes are PS
      heparin and PSN suramin. They vary in their backbone structure, length,
      number/disposition of sulfated/sulfonated groups. Different combinations of these
      features confer to PS/PSN the capacity to bind with variable specificity to those
      heparin-binding proteins that "cross-contribute" to virus infection and tumor
      progression. Taken together, these considerations suggest that heparin-like
      PS/PSN antagonists may act as multitarget drugs that may control at once virus
      infection and tumor progression by targeting different proteins simultaneously.
      Here we discuss the possibility to exploit PS/PSN compounds for the development
      of drugs at the cross-road of viral infection and oncogenesis, taking in
      consideration the past efforts, possible drawbacks and future perspectives.

PMID- 19754372
TI  - Dendrimers: a class of polymers in the nanotechnology for the delivery of active
      pharmaceuticals.
AB  - Dendrimers represent a class of novel polymers having unique molecular
      architectures characterized by their well-defined structure, with a high degree
      of molecular uniformity, low polydispersity and properties that make them
      attractive materials for the development of nanomedicines. The dendrimer drug
      delivery can be achieved by coupling a drug through one of two approaches.
      Hydrophobic drugs can be complexed within the hydrophobic dendrimer interior to
      make them water-soluble or drugs can be covalently coupled onto the surface of
      the dendrimer. In addition, dendrimers have been shown to be capable of bypassing
      efflux transporters. A new generation of dendrimer-based delivery systems will
      enable the efficient transport of drugs across cellular barriers. This review
      deals principally with the synthesis, characterization and recent applications of
      dendrimers. In future it will only ever be possible to designate a dendrimer as
      safe means of drug delivery related to a specific application. However, so far
      limited clinical experience using dendrimers makes it impossible to designate any
      particular system which is safe and non toxic. Although there is widespread
      concern as to the safety of nanosized particles, preclinical and clinical
      experience gained during the development of polymeric excipients, biomedical
      polymers and polymer therapeutics showed that judicious development of dendrimer
      chemistry for each specific application will ensure development of safe and
      important materials for biomedical and pharmaceutical use.

PMID- 19754373
TI  - Hybrid drugs for malaria.
AB  - Malaria continues to devastate much of the tropics and sub-tropics in spite of
      the availability of a number of antimalarial drugs. Part of this problem is due
      to the disadvantages of the drugs in use, which include (depending on the drug)
      side effects, reduced efficacy due to resistance, and high cost. Multiple
      traditional and novel approaches to the discovery and design of new antimalarial
      agents are likely to be required to furnish the new drugs necessary for improved
      malaria control. This review will address one novel and emerging approach, namely
      the development of hybrid antimalarial agents composed of two distinct
      antimalarial moieties joined covalently. Particular emphasis will be placed on
      the properties of the hybrids' design, including biological activity, advantages
      over other approaches, and the potential to address issues relating to
      resistance, solubility and formulation/delivery. The review will discuss the
      synthetic methodology used to form the hybrid and the ease by which it may be
      cleaved to form the independent components in vivo. The molecules discussed
      include hybrids of (i) artemisinins or other endoperoxide-based agents and
      quinolines (e.g. trioxaquines), (ii) chloroquine or other aminoquinolines and
      resistance-reversing or other agents, and (iii) peptidase inhibitors and other
      agents. The actual and potential advantages and disadvantages of such hybrids in
      relation to established single drugs or drug combinations will be discussed
      critically and promising future directions highlighted.

PMID- 19754374
TI  - Oxidative stress and cellular homeostasis.

PMID- 19754375
TI  - Oxidative stress, endothelial dysfunction and atherosclerosis.
AB  - This review focuses on the role of oxidative processes in atherosclerosis and the
      cardiovascular diseases (CVD) that can arise as a result. Atherosclerosis
      represents a state of heightened oxidative stress characterized by lipid and
      protein oxidation in the vascular wall. Overproduction of reactive oxygen species
      (ROS) under pathophysiologic conditions forms an integral part of the development
      of CVD, and in particular atherosclerosis. Endothelial dysfunction, characterized
      by a loss of nitric oxide (NO) bioactivity, occurs early on in the development of
      atherosclerosis, and determines future vascular complications. Although the
      molecular mechanisms responsible for mitochondria-mediated disease processes are
      not clear, oxidative stress seems to play an important role. In general, ROS are
      essential to the functions of cells, but adequate levels of antioxidant defenses
      are required in order to avoid the harmful effects of excessive ROS production.
      In this review, we will provide a summary of the cellular metabolism of reactive
      oxygen species (ROS) and its role in pathophysiological processes such as
      atherosclerosis; and currently available antioxidants and possible reasons for
      their efficacy and inefficacy in ameliorating oxidative stress-mediated diseases.

PMID- 19754376
TI  - An update of the oxidation-inflammation theory of aging: the involvement of the
      immune system in oxi-inflamm-aging.
AB  - The aging process is one of the best examples of the effects of a deterioration
      of homeostasis, since aging is accompanied by an impairment of the physiological
      systems including the homeostatic systems such as the immune system. We propose
      an integrative theory of aging providing answers to the how (oxidation), where
      first (mitochondria of differentiated cells) and why (pleiotropic genes) this
      process occurs. In agreement with this oxidation-mitochondrial theory of aging,
      we have observed that the age-related changes of immune functions have as their
      basis an oxidative and inflammatory stress situation, which has among its
      intracellular mechanisms the activation of NFkappaB in immune cells. Moreover, we
      have also observed that several functions of immune cells are good markers of
      biological age and predictors of longevity. Based on the above we have proposed
      the theory of oxidation-inflammation as the main cause of aging. Accordingly, the
      chronic oxidative stress that appears with age affects all cells and especially
      those of the regulatory systems, such as the nervous, endocrine and immune
      systems and the communication between them. This fact prevents an adequate
      homeostasis and, therefore, the preservation of health. We have also proposed a
      key involvement of the immune system in the aging process of the organism,
      concretely in the rate of aging, since there is a relation between the redox
      state and functional capacity of the immune cells and the longevity of
      individuals. Moreover, the role of the immune system in senescence could be of
      universal application. A confirmation of the central role of the immune system in
      oxi-inflamm-aging is that the administration of adequate amounts of antioxidants
      in the diet, improves the immune functions, decreasing their oxidative stress,
      and consequently increases the longevity of the subjects.

PMID- 19754377
TI  - Cross-talk between oxidative stress and pro-inflammatory cytokines in acute
      pancreatitis: a key role for protein phosphatases.
AB  - Acute pancreatitis is an acute inflammatory process localized in the pancreatic
      gland that frequently involves peripancreatic tissues. It is still under
      investigation why an episode of acute pancreatitis remains mild affecting only
      the pancreas or progresses to a severe form leading to multiple organ failure and
      death. Proinflammatory cytokines and oxidative stress play a pivotal role in the
      early pathophysiological events of the disease. Cytokines such as interleukin
      1beta and tumor necrosis factor alpha initiate and propagate almost all
      consequences of the systemic inflammatory response syndrome. On the other hand,
      depletion of pancreatic glutathione is an early hallmark of acute pancreatitis
      and reactive oxygen species are also associated with the inflammatory process.
      Changes in thiol homestasis and redox signaling decisively contribute to
      amplification of the inflammatory cascade through mitogen activated protein
      kinase (MAP kinase) pathways. This review focuses on the relationship between
      oxidative stress, pro-inflammatory cytokines and MAP kinase/protein phosphatase
      pathways as major modulators of the inflammatory response in acute pancreatitis.
      Redox sensitive signal transduction mediated by inactivation of protein
      phosphatases, particularly protein tyrosin phosphatases, is highlighted.

PMID- 19754378
TI  - Protein pool maintenance during oxidative stress.
AB  - The production of reactive species causes oxidative modifications of proteins
      accompanied by a loss of protein function. By protein oxidation all cellular
      compartments and any amino acid are effected. This might result in a defect of
      cellular homeostasis. Therefore, the degradation of non-functional, oxidized
      proteins is an essential function of the proteolytic branch of the antioxidant
      defense machinery. The major proteolytic system responsible for the removal of
      oxidized proteins is the proteasomal system. Whereas moderately oxidized proteins
      are more sensitive to proteolytic attack, severely oxidized ones are often poor
      substrates and might, however, inhibit the proteasome. This paper reviews the
      data available on protein modifications following oxidative stress, the cellular
      responses and the role of proteasome in this process.

PMID- 19754379
TI  - Mitochondrial-targeted antioxidants and oxidative stress: a proteomic prospective
      study.
AB  - Mitochondria produce large amounts of free radicals and play an important role in
      the life and death of a cell, regulating the signalling, metabolism, and energy
      production needed for cellular function. In this way, mitochondrial oxidative
      damage and dysfunction contribute to a number of cell pathologies that are
      manifested through a range of conditions that include cardiovascular diseases
      (CVD). Although the molecular mechanisms responsible for mitochondria-mediated
      disease processes are not yet completely understood, oxidative stress definitely
      seems to play an important role. When examined at the protein level, both
      expression levels and protein modifications are altered by oxidative stress.
      While these effects have been studied in the past by classic biochemical methods,
      recent developments in proteomics have allowed the oxidative stress response to
      be studied in more depth. The focus of this work is the mitochondrial
      proteome/genome interplay that is currently believed to be implicated in a range
      of human diseases. Particular attention is given to the current knowledge of the
      role of mitochondria in the development of oxidative-stress-based diseases; e.g.
      CVD is highlighted together with the prospective proteomics perspective as an
      alternative prognostic and diagnostic tool for interpreting many mitochondria
      related anomalies. Accordingly, strategies for the targeted delivery of
      antioxidants to mitochondria are being developed. The insight provided by recent
      proteomic research and the effects of mitochondrial-antioxidants on possible
      interventions are also discussed.

PMID- 19754380
TI  - Antioxidant effects of natural bioactive compounds.
AB  - Reactive oxygen species (ROS), as well as reactive nitrogen species (RNS) play
      either harmful or beneficial role in biological systems. Beneficial effects of
      ROS include physiological roles in cellular responses against infectious agents
      and in several cellular signalling pathways. Harmful effects are due to high
      concentrations of ROS, which can damage biomolecules, including lipids, proteins
      and nucleic acids. The harmful effects of ROS are counterbalanced by the
      antioxidant action of both antioxidant enzymes and non-enzymatic antioxidants;
      however, despite the presence of the cell's antioxidant system, oxidative damage
      accumulates during the life cycle and has been proposed to play a pivotal role in
      the development of age-dependent diseases such as atherosclerosis, arthritis,
      neurodegenerative disorders and cancer. Numerous epidemiological studies indicate
      that a reduced risk of various lifestyle diseases, mainly cardiovascular diseases
      and cancer, as well as other disorders, is associated to a diet rich in fruits,
      vegetables and their products. The drive to enhance the consumption of fruits and
      vegetables in the human diet is linked with positive effects of beneficial
      antioxidants impacting on health promotion. In this review we present an outline
      of main roles of ROS in biological processes and diseases and how natural
      bioactive compounds of fruits and vegetables determine their health-promoting
      properties.

PMID- 19754381
TI  - Mechanisms involved in metformin action in the treatment of polycystic ovary
      syndrome.
AB  - The N, N' dimethyl-biguanide : Metformin is an antidiabetic drug that increases
      glucose utilization in insulin-sensitive tissues. As Polycystic Ovary Syndrome
      (PCOS) and diabetes share some altered parameters-such as abnormal glucose:
      insulin ratio, altered lipidic metabolism and insulin-resistance syndrome- the
      use of metformin has become increasingly accepted and widespread in the treatment
      of PCOS. Currently, metformin is used to induce ovulation and during early
      pregnancy in PCOS patients, however, a complete knowledge of the metformin action
      has not been achieved yet. This review describes beyond the classical
      reproductive action of metformin and explores other benefits of the drug. In
      addition, the present work discusses the molecular mechanisms involved further
      than the classical pathway that involves the AMP-activated protein kinase.

PMID- 19754382
TI  - The oxidative stress menace to coronary vasculature: any place for antioxidants?
AB  - Oxidative stress is involved in the pathogenesis of atherosclerosis. A variety of
      antioxidants has been used in clinical studies, during the past few years, for
      the prevention and treatment of atherosclerosis. In small clinical studies it was
      found that both vitamins C and E may improve endothelial function in high risk
      patients. However, interventional trials have been controversial, with some
      positive findings, many null findings, and some suggestion of harm in certain
      high-risk populations. Therefore, treatment with antioxidant vitamins C and E
      should not be recommended for the prevention or treatment of coronary
      atherosclerosis. New antioxidant strategies are needed to clarify the exact role
      of antioxidant treatment in coronary atherosclerosis.

PMID- 19754383
TI  - Drugs targeting atherosclerosis: current and emerging approaches.

PMID- 19754384
TI  - Anti-atherosclerotic molecules targeting oxidative stress and inflammation.
AB  - The accumulation of lipids within arteries remains to be the initial impulse for
      the pathogenesis of atherosclerosis; however, both inflammation and oxidative
      stress are considered to play a critical role in this process. Several lipid
      lowering drugs are used as the first line therapy in atherosclerosis; however,
      different agents have been found to exhibit beneficial effects which are
      independent of their lipid lowering activity. Both statins and fibrates have been
      reported to exert anti-inflammatory and anti-oxidative effects in addition to
      their anti-atherosclerotic actions. Furthermore, anti-hypertensive, anti-diabetic
      and anti-platelet drugs, which reduce oxidative stress and inflammation, have
      been shown to attenuate atherosclerosis. In addition, novel substances such as
      HDL-related agents, cyclopentenone prostaglandins, lipoprotein-associated
      phospholipase A(2) inhibitors, 5-lipoxygenase pathway inhibitors, acyl CoA:
      cholesterol acyltransferase inhibitors, analogues of probucol and
      lysophosphatidic acid antagonists have been developed for the treatment of
      atherosclerosis as a consequence of their actions on oxidative stress and
      inflammation. The present article reviews the involvement of inflammation and
      oxidative stress in the pathogenesis of atherosclerosis and focuses on the
      mechanisms of some clinically used as well as potential anti-atherosclerotic
      substances with anti-inflammatory and anti-oxidative properties.

PMID- 19754385
TI  - Rho kinase: an important mediator of atherosclerosis and vascular disease.
AB  - Atherosclerosis is a complex inflammatory process characterized by the cross-talk
      between excessive inflammation and lipid accumulation. In the past few years,
      compelling evidence suggests that statins can decrease vascular inflammation and
      attenuate the development of atherosclerosis through their so-called "pleiotropic
      effects". These cholesterol-independent effects are predominantly due to their
      ability to inhibit isoprenoid synthesis. In particular, inhibition of
      geranylgeranylpyrophosphate synthesis leads to inhibition of Rho and its
      downstream target, Rho-kinase (ROCK). Thus, one of the beneficial effects of
      statin therapy could be due to inhibitory effects on ROCK. ROCK is involved in
      mediating diverse cellular functions such as smooth muscle contraction, cell
      migration and proliferation. While increased ROCK activity is associated with
      endothelial dysfunction, cerebral ischemia, coronary vasospasms and metabolic
      syndrome, the inhibition of ROCK by statins or selective ROCK inhibitors leads to
      up-regulation of endothelial nitric oxide synthase (eNOS), decreased vascular
      inflammation, and reduced atherosclerotic plaque formation. This review will
      focus on the impact of ROCK in cardiovascular disease and its contributory role
      to vascular inflammation and the atherosclerosis.

PMID- 19754386
TI  - Inhibitors of the 5-lipoxygenase pathway in atherosclerosis.
AB  - The inflammatory environment within the atherosclerotic lesion stimulates the 5
      lipoxygenase pathway of arachidonic acid metabolism, leading to the biosynthesis
      of the potent lipid inflammatory mediators leukotrienes. The present review
      summarizes the components of this pathway; the enzymes 5-lipoxygenase (5-LO,
      ALOX5) with its activating protein, FLAP (ALOX5AP), LTA(4) hydrolase and LTC(4)
      synthase, as well as the receptors for leukotriene B(4) (BLT(1) and BLT(2)) and
      cysteinyl-leukotrienes (CysLT(1) and CysLT(2)), respectively. Genetic variations
      within the genes encoding these proteins have been associated with cardiovascular
      risk. Inhibiting the 5-lipoxygenase pathway through either leukotriene synthesis
      inhibitors or leukotriene receptor antagonists in experimental models of
      atherosclerosis has however generated contradictory results. Several inhibitors
      of the 5-lipoxygenase pathway are now evaluated in clinical trials of patients
      with cardiovascular disease.

PMID- 19754387
TI  - Prevention of atherosclerosis by interference with the vascular nitric oxide
      system.
AB  - Nitric oxide (NO) produced by endothelial NO synthase (eNOS) represents an anti
      atherosclerotic principle. NO bioavailability is decreased in atherosclerosis due
      to increased NO inactivation by reactive oxygen species and reduced NO synthesis.
      Various types of vascular pathophysiology are associated with oxidative stress,
      with NADPH oxidases as the major source of reactive oxygen species. These
      inactivate NO. Also, oxidative stress is likely to be the main cause for
      oxidation of the essential NOS cofactor, tetrahydrobiopterin (BH(4)). A lack of
      BH(4) leads to eNOS uncoupling (i.e., uncoupling of oxygen reduction from NO
      synthesis in eNOS). Based on these pathomechanisms, the therapeutic potential of
      a number of compounds is discussed in this review: (1) NO donors; (2) L-arginine;
      (3) folic acid; (4) BH(4) and its precursor sepiapterin; (5) compounds that
      upregulate eNOS and concomitantly maintain eNOS activity (e.g. midostaurin,
      betulinic acid, ursolic acid, AVE9488 and AVE3085); (6) compounds that enhance
      the de novo synthesis of BH(4) by stimulating expression or activity of GTP
      cyclohydrolase I; and (7) 3-hydroxy-3-methylglutaryl-coenzyme A inhibitors
      (statins) and drugs interrupting the renin-angiotensin-aldosterone system.
      Statins, angiotensin II type 1 receptor blockers, angiotensin-converting enzyme
      (ACE) inhibitors, the aldosterone antagonist eplerenone and the renin inhibitor
      aliskiren enhance NO bioactivity and reduce atherosclerosis progression through
      multiple mechanisms.

PMID- 19754388
TI  - Recent advances on the antiatherogenic effects of HDL-derived proteins and
      mimetic peptides.
AB  - The plasma levels of high-density lipoprotein (HDL) cholesterol are inversely
      correlated with the risk of atherosclerosis and cardiovascular disease (CVD) in
      humans. One of the major mechanisms whereby HDL particles protect against
      atherosclerosis is that of reverse cholesterol transport from atherosclerotic
      lesion macrophages to the liver. HDL particles also exhibit various
      antiatherogenic and cardioprotective effects by modulating the function of
      various cells including the cells of the artery wall and by expressing
      antioxidant, anti-inflammatory, antithrombotic and antiapoptotic effects. Most
      these effects are mediated by various lipid and protein HDL components. A
      plethora of studies have been conducted in order to shed light on the mechanisms
      by which each HDL component contributes to the functionality of this lipoprotein.
      The complete elucidation of these mechanisms will significantly contribute to
      current efforts focused on the development of therapeutic strategies to promote
      the antiatherogenic potency of HDL. The present review discusses current
      knowledge on the biological activities of the major apolipoproteins and enzymes
      associated with HDL, which may significantly contribute to the overall
      antiatherogenic and cardioprotective effects of this lipoprotein.

PMID- 19754389
TI  - EP2300 compounds: focusing on the antiatherosclerotic properties of squalene
      synthase inhibitors.
AB  - Although treatment with statins significantly reduces adverse cardiovascular
      outcomes, several studies have shown that cardiovascular events continue to occur
      in two thirds of all patients. A logical pharmacologic approach to further reduce
      cardiovascular disease mortality should be focused on direct modifiers of
      atherosclerosis or lipid-modifying agents with different mechanism of action than
      existing drugs against dyslipidemia. Squalene synthase inhibitors can decrease
      circulating low-density lipoprotein (LDL)-cholesterol by an increased expression
      of hepatic LDL receptors in a similar manner to statins. Also, depending on their
      structure, they may possess antiatherosclerotic properties independent of their
      lipid-modifying effects. This review, following a brief introduction to different
      classes of squalene synthase inhibitors and representative molecules, presents
      the accumulating in vitro and in vivo experimental evidence relevant to squalene
      synthase inhibitors EP2306 and EP2302 and discusses their properties. EP2306 and
      EP2302 show a similar inhibitory effect in the progression of atherosclerosis in
      the cholesterol-fed rabbit. Moreover, EP2306 showed a significant long-term
      antiatherosclerotic effect not shared by simvastatin or their combination in this
      animal model. EP2302 also showed a favorable effect in the regression of pre
      established atherosclerotic lesions. It is reasonable to hypothesize that EP2302,
      due to its NO-releasing and enhancing properties, could have additional
      advantages compared to EP2306. Treatment with EP2300 compounds did not adversely
      affect liver transaminases or cause toxicity on various organs of the cholesterol
      fed rabbit. The satisfactory safety profile of EP2300 compounds in this animal
      model is a promising finding in view of future clinical studies.

PMID- 19754390
TI  - Oral antidiabetic agents: anti-atherosclerotic properties beyond glucose
      lowering?
AB  - Type 2 diabetes is associated with substantially increased cardiovascular
      mortality. The need to reduce the progression of atherosclerosis alongside
      lowering blood glucose levels is now well established. Ideally, pharmaceutical
      treatment should address both of these needs. This review summarises current
      evidence of the anti-atherosclerotic effects exerted by oral antidiabetic agents.
      Metformin has so far consistently succeeded in reducing cardiovascular morbidity
      and mortality and exerting beneficial effects on lipids. Of the new agents,
      thiazolidinediones (rosiglitazone and pioglitazone) have been most widely
      studied. They have a favourable effect on fat distribution and improve lipid
      profile, fibrinolysis and endothelial function. Moreover, they reduce blood
      pressure and inflammatory markers, attenuate the progression of carotid intima
      media thickness (CIMT) and may reduce the rates of coronary restenosis following
      percutaneous coronary intervention. Glinides (repaglinide and nateglinide) have
      also been documented to improve endothelial function and lipid profile, to reduce
      oxidative stress, platelet activity and inflammatory markers, and to diminish the
      progression of CIMT. Finally, acarbose may significantly reduce new cases of
      hypertension and cardiovascular events, as well as diminishing the progression of
      CIMT in patients with impaired glucose tolerance. Interestingly, some of these
      beneficial effects appear to be independent of the antidiabetic action. Thus,
      oral antidiabetic agents are now emerging as useful tools for the attenuation of
      the atherosclerotic activity and for the protection of the vasculature in
      patients with type 2 diabetes.

PMID- 19754391
TI  - Genomics and the prospects of existing and emerging therapeutics for
      cardiovascular diseases.
AB  - The growing knowledge about genetic influence on cardiovascular diseases (CVD)
      combined with the recently generated amounts of genomic data hold promise to the
      identification of new markers for atherosclerotic CVD. Cardiovascular
      pharmacogenomics and pharmacogenetics have now the potential for leading to
      identification of genetic contributors and therefore to the development of
      predictive genetic tests that could optimize drugs efficacy and minimize
      toxicity. Clinical studies have shown that genetic variations within cytochromes
      P450 (CYPs), 3-Hydroxyl-3-Methylglutaryl Coenzyme A Reductase (HMGCR) and
      apolipoprotein E (APOE) genes influence individual's response to lipid lowering
      statins. Furthermore, development of antagonists or inhibitors of molecules such
      as peroxisome proliferator-activated receptors (PPARs), lipoprotein-associated
      phospholipase A(2) (Lp-PLA(2)), angiotensin-converting enzyme (ACE), angiotensin
      receptors and tumor necrosis factor (TNF)-alpha could be another alternative to
      prevent atherosclerosis. In addition, novel molecules under the name of biologics
      including family of peptides such as atrial natriuretic peptide (ANP) and brain
      natriuretic peptide (BNP), urocortin, apelin and antimicrobial peptides (AMPs)
      could be considered as new targets for the prevention and treatment of CVD. In
      this article, we will focus mainly on recent genomic advances in the development
      of new markers and therapeutic agents for CVD. We present an array of molecules
      that could have pharmacological benefit for the treatment of heart disease. We
      also discuss in details new strategies including biologics, which are actually
      the focus of companies for clinical development of therapeutic drugs. All these
      efforts provide optimism and attractive promise to cure CVD.

PMID- 19754392
TI  - Structure- and ligand-based drug design: advances and perspectives.

PMID- 19754394
TI  - Structure-based drug design strategies in medicinal chemistry.
AB  - A broad variety of medicinal chemistry approaches can be used for the
      identification of hits, generation of leads, as well as to accelerate the
      development of high quality drug candidates. Structure-based drug design (SBDD)
      methods are becoming increasingly powerful, versatile and more widely used. This
      review summarizes current developments in structure-based virtual screening and
      receptor-based pharmacophores, highlighting achievements as well as challenges,
      along with the value of structure-based lead optimization, with emphasis on
      recent examples of successful applications for the identification of novel active
      compounds.

PMID- 19754393
TI  - Docking screens: right for the right reasons?
AB  - Whereas docking screens have emerged as the most practical way to use protein
      structure for ligand discovery, an inconsistent track record raises questions
      about how well docking actually works. In its favor, a growing number of
      publications report the successful discovery of new ligands, often supported by
      experimental affinity data and controls for artifacts. Few reports, however,
      actually test the underlying structural hypotheses that docking makes. To be
      successful and not just lucky, prospective docking must not only rank a true
      ligand among the top scoring compounds, it must also correctly orient the ligand
      so the score it receives is biophysically sound. If the correct binding pose is
      not predicted, a skeptic might well infer that the discovery was serendipitous.
      Surveying over 15 years of the docking literature, we were surprised to discover
      how rarely sufficient evidence is presented to establish whether docking actually
      worked for the right reasons. The paucity of experimental tests of theoretically
      predicted poses undermines confidence in a technique that has otherwise become
      widely accepted. Of course, solving a crystal structure is not always possible,
      and even when it is, it can be a lot of work, and is not readily accessible to
      all groups. Even when a structure can be determined, investigators may prefer to
      gloss over an erroneous structural prediction to better focus on their discovery.
      Still, the absence of a direct test of theory by experiment is a loss for method
      developers seeking to understand and improve docking methods. We hope this review
      will motivate investigators to solve structures and compare them with their
      predictions whenever possible, to advance the field.

PMID- 19754395
TI  - Prospective ligand- and target-based 3D QSAR: state of the art 2008.
AB  - As drug discovery and development has grown ever riskier and more expensive,
      interest has increased in using computational tools to identify good candidates
      more quickly and to avoid investing resources in synthesizing and testing
      compounds that are not likely to succeed. The most powerful of these tools seek
      to exploit the connection between the three-dimensional (3D) structure of a
      molecule and its various biological activities. Two fundamentally different ways
      of addressing this challenge have arisen over the years: ligand-based methods
      that seek to identify and exploit similarities between the structures of ligands
      that are known to bind to a given target; and target-based (docking) methods that
      seek to identify and exploit complementarities to the binding site itself. The
      structure-activity relationships involved reflect the interplay of many
      thermodynamic factors, which makes putting them on any kind of quantitative
      footing a challenge. The progress being made in coming to grips with that
      challenge is assessed here through a survey of recently published prospective
      studies, a review of the underlying problems remaining, and consideration of some
      ways in which different methods are being combined to improve overall
      performance.

PMID- 19754396
TI  - Spin-lattice relaxation time in drug discovery and design.
AB  - NMR is one of the most powerful techniques for ligand-biomolecule interaction
      studies and drug screening and design. There are several methods that are
      strongly used, including chemical shift perturbation (CSP), saturation transfer
      difference (STD) and diffusion coefficients. However, one of the most useful and
      easy to apply NMR parameters in medicinal chemistry studies is the spin-lattice
      relaxation data, which can be employed to investigate the strength and topology
      of intermolecular interactions, such as drug-drug, drug-protein, drug-DNA, drug
      micelle (or vesicle) and biomolecule-biomolecule interactions. This review deals
      with the newest applications of T(1) in different studies of interest for drug
      design and evaluation.

PMID- 19754397
TI  - Structure-based drug discovery for tropical diseases.
AB  - Parasitic diseases are amongst the foremost threats to human health and welfare
      around the world. In tropical and subtropical regions of the world, the
      consequences of parasitic infections are devastating both in terms of human
      morbidity and mortality. The current available drugs are limited, ineffective,
      and require long treatment regimens. To overcome these limitations, the
      identification of new macromolecular targets and small-molecule modulators is of
      utmost importance. The advances in genomics and proteomics have prompted drug
      discovery to move toward more rational strategies. The increasing understanding
      of the fundamental principles of protein-ligand interactions combined with the
      availability of compound libraries has facilitated the identification of
      promising hits and the generation of high quality lead compounds for tropical
      diseases. This review presents the current progresses and applications of
      structure-based drug design (SBDD) for the discovery of innovative chemotherapy
      agents for a variety of parasitic diseases, highlighting the challenges,
      limitations, and future perspectives in medicinal chemistry.

PMID- 19754398
TI  - Steroid hormone binding receptors: application of homology modeling, induced fit
      docking, and molecular dynamics to study structure-function relationships.
AB  - Steroid nuclear hormone binding receptors (SHRs) are ligand activated
      transcription factors involved in the regulation of target genes associated with
      key physiological and developmental processes. As such they are important targets
      for drug discovery. Crystal structures are now available for all members of the
      SHR family, however, earlier studies carried out using homology models proved to
      be quite valuable for understanding the binding of natural ligands and for
      designing novel therapeutic agents. The maleability of the binding pocket means
      that the crystal structure of an SHR in complex with one ligand may not suffice
      to explain the binding interactions of that same target with a different ligand.
      Consequently, induced fit docking and molecular dynamics are shown to be useful
      and necessary tools for understanding these receptors.

PMID- 19754399
TI  - Parkinson's disease.

PMID- 19754400
TI  - Half a century of L-DOPA.
AB  - L-DOPA is a di-hydroxy-phenyl, catecholamine precursor, amino acid, initially
      considered as an inert compound and now the key stone for the treatment of
      Parkinson's disease (PD) and some hereditary dystonias. L-DOPA, when administered
      to mammals, is rapidly metabolized to dopamine and 3-OM-DOPA, and its half-life
      in plasma is roughly 2 hours which has been considered the explanation for some
      of the L-DOPA related complications in PD. There have been, therefore,
      sophisticated methods of improving its pharmacokinetics by the association of
      decarboxylase and COMT inhibitors, slow release preparations and continuous
      infusions. In addition to its symptomatic effects, the impact of L-DOPA on the
      natural course of the disease is intriguing. By alleviating motor deficits, L
      DOPA may improve health quality and life span in patients with PD, but there are
      neurotoxic and neurotrophic effects of L-DOPA which may produce long term effects
      on disease progression. These effects are dependent of the dose, the status of
      the metabolic pathways involved in catecholamine metabolism, the balance of free
      radicals and their scavengers and the function of glia. Finally, there is new
      data suggesting that L-DOPA may be not only a catecholamine precursor but also a
      neurotransmitter by itself of yet unknown function.

PMID- 19754401
TI  - The role of transcription factor Pitx3 in dopamine neuron development and
      Parkinson's disease.
AB  - Parkinson's disease (PD) is characterized by the selective loss of dopamine (DA)
      neurons in the substantia nigra compacta (SNc). The transcription factor Pitx3 is
      important for the differentiation and maintenance of midbrain DA neurons during
      development. There is highly restricted and constitutive expression of Pitx3 in
      the SNc and ventral tegmental area (VTA) of the midbrain after birth. In addition
      to its importance during development, Pitx3 also has roles in the long-term
      survival and maintenance of the midbrain DA neurons. In this review, we discuss
      the function of Pitx3 throughout the life of midbrain neurons and the
      contribution of Pitx3 to disease mechanisms.

PMID- 19754402
TI  - Etiopathogenesis and treatment of Parkinson's disease.
AB  - Parkinson's disease (PD) is a complex neurodegenerative disorder characterised by
      dopaminergic cell loss in the substantia nigra. In addition, neurodegeneration
      occurs at a number of extra-nigral locations and involves a variety of non
      dopaminergic neurotransmitter systems. Etiopathogenic mechanisms leading to cell
      death include oxidative stress and free radical generation, mitochondrial
      dysfunction, glutamate receptor mediated excitotoxicity, inflammation,
      oligodendrocytic interaction and neurotrophic factors, ubiquitin-proteosome
      system involvement, autophagy and apoptosis. Each of these is a potential target
      for novel pharmacotherapies including bioenergetic agents, inhibitors of
      excitotoxicity, neurotrophic factors, proteosomal enhancers and anti-apoptotic
      agents. Evidence has also been gained from cell culture and animal models for the
      potential disease modifying action of currently available dopaminergic therapies.
      These drugs have undergone clinical evaluation using studies with novel designs
      including "delayed start" methodology and studies using neuroimaging as a
      surrogate marker of dopaminergic cell loss. It is estimated from clinical,
      pathological and imaging studies that at least 50% of dopaminergic neurons are
      lost before the development of significant motor symptoms with a pre-motor phase
      of approximately 6-8 years. A number of pre- and post-synaptic neuroplastic
      homeostatic mechanisms occur during this period to maintain motor function.
      However these changes have been implicated in the development of motor
      complications (wearing "off" and dyskinesias). The evidence for treatments of
      motor complications in PD is discussed as are potential non-dopaminergic
      therapeutic targets to delay or improve motor complications.

PMID- 19754403
TI  - The role of autophagy on the survival of dopamine neurons.
AB  - Autophagy is the mechanism through which cells degrade oxidized membranes
      organelles and mis/unfolded proteins, in this latter function cooperating with
      the ubiquitin-proteasome system (UP system). Although autophagy has been known
      for a long time, its involvement in the pathogenesis of neurodegenerative
      diseases has been investigated only recently. The most fascinating data are very
      recent and show an impressive connection between proteins that are mutated in
      different forms of familial Parkinson's Disease (PD) and the critical role that
      these proteins play in the physiology of the Autophagy (ATG) pathway. This
      evidence is supported by neuropathological data showing at the ultrastructural
      level, the occurrence of an altered ATG in the dopamine (DA) neurons of the
      Substantia Nigra of patients affected by PD. Accordingly, by using experimental
      models of PD the involvement of ATG is documented as well. In particular,
      administration of the DA neurotoxin methamphetamine produces damage to DA
      containing cells which is exacerbated and results in neuronal cell death when the
      ATG pathway is inhibited, thus confirming ATG as a critical pathway for the
      survival of DA neurons. In the present manuscript, after describing the general
      molecular and cellular features of ATG, we give a short overview of the most
      relevant aspects concerning the involvement of ATG in the pathogenesis of PD. We
      further propose that the ATG and the UP systems might converge in the formation
      of a so-called "autophagoproteasome" which might represent an early
      ultrastructure witnessing the presence of an ongoing degeneration within DA
      cells.

PMID- 19754404
TI  - Behavioural sensitisation during dopamine replacement therapy in Parkinson's
      disease is reminiscent of the addicted brain.
AB  - The intermittent oral intake of the dopamine (DA) precursor L-3,4
      dihydroxyphenylalanine (L-DOPA) is the classic therapy of Parkinson's disease
      (PD). In this way, the drug precursor can be metabolised into the active
      neurotransmitter DA. Although this occurs throughout the brain, the therapeutic
      relief is believed to be due to restoring extracellular DA levels within the
      dorsal striatum (more in the putamen than the caudate nucleus) which lacks
      endogenous DA as a consequence of the disease process. However, differing from
      physiological DA transmission, this therapeutic pattern leads to abnormal peaks
      of non-synaptic DA, which are supposed to trigger behavioural sensitisation
      expressed as abnormal involuntary movements. A similar pattern of abnormal DA
      stimulation occurs during methamphetamine (METH) intake. In the present review we
      will provide evidence showing the similarities between METH- and L-DOPA-induced
      DA stimulation with an intact and denervated striatum respectively. This
      comparison will encompass various features; the timing, the areas and the amount
      of extracellular DA levels which reveal surprising homologies. Such an
      overlapping between L-DOPA in PD and METH will be further analysed to critically
      assess the commonalities concerning the following points: abnormal receptor
      stimulation, recruitment of altered transduction pathways, abnormal gene
      expression, alterations in the phenotype of striatal neurons, and the
      establishment of behavioural sensitisation which appear as distinct phenomena
      (i.e. abnormal involuntary movements in PD and drug addiction in METH abuse);
      nonetheless, this may also lead to common behavioural alterations (METH-like
      addictive behaviours in PD patients during the course of DA replacement therapy
      in subsets of PD patients).

PMID- 19754406
TI  - New molecular avenues in Parkinson's disease therapy.
AB  - Idiopathic Parkinson's Disease (PD) is a progressive neurodegenerative disease
      characterized by dopaminergic neuronal loss within the substantia nigra. The
      degeneration of dopamine and other neuronal populations in PD lead to both
      chronic motor and non-motor disabilities but the mechanisms remain unclear.
      Molecular genetic studies in familial forms of the disease identified key
      proteins involved in PD pathogenesis, supporting a major role for (i) protein
      aggregation and neurotoxic alpha-synuclein oligomeric species due to an altered
      protein quality control, (ii) parkin-driven deregulation of the ubiquitin
      proteasome system, (iii) oxidative stress and mithocondrial dysfunction, and,
      finally, (iv) disturbed kinase activity. The elucidation of these new molecular
      pathways has increased our knowledge of PD pathophysiology, but it remains an
      open question whether alterations of these pathways lead to different entities of
      PD or whether they finally converge at a point that is the common pathogenetic
      denominator of PD. However, the knowledge of validated targets is in its infancy,
      and thus, traditional target-based drug discovery strategies are of limited use.
      Alternative approaches are needed, and early attempts were aimed at identifying
      molecules inhibiting the aggregation of alpha-synuclein fragments, interfering
      with the ubiquitin proteasome pathway and reducing oxidative stress. Such
      discovery strategies have an impact on the configuration of screening cascades
      for effective translation of drug candidates toward clinical trials. This review
      examines how these genetic findings provided us with suitable animal models and
      how the gained insights will contribute to better therapies for PD.

PMID- 19754407
TI  - Recent progress in the development of mGluR4 positive allosteric modulators for
      the treatment of Parkinson's disease.
AB  - This article describes recent advances in the development and biological
      evaluation of small molecule mGluR4 positive allosteric modulators (PAMs), and,
      to a lesser extent, orthosteric agonists. Due to its expression in the basal
      ganglia, the Family 3 GPCR metabotropic glutamate receptor subtype 4 (mGluR4) has
      recently garnered a great deal of attention as a putative target for the
      treatment of Parkinson's disease and a variety of other CNS disorders. Until
      2008, with the exception of the prototypical mGluR4 PAM (-)-PHCCC, very few small
      molecule tools existed to probe the role of selective activation of mGluR4. This
      review will focus on the explosion of novel mGluR4 PAMs reported in the past year
      and the further preclinical validation of mGluR4 activation as a potentially
      groundbreaking treatment for Parkinson's disease.

PMID- 19754405
TI  - Cognitive impairment and dementia in patients with Parkinson disease.
AB  - Parkinson disease (PD) is an already prevalent neurodegenerative disease that is
      poised to at least double over the next 25 years. Although best known for its
      characteristic movement disorder, PD is now appreciated commonly to cause
      cognitive impairment, including dementia, and behavioral changes. Dementia in
      patients with PD is consequential and has been associated with reduced quality of
      life, shortened survival, and increased caregiver distress. Here we review
      clinical presentation and progression, pathological bases, identification of
      genetic risk factors, development of small molecule biomarkers, and emerging
      treatments for cognitive impairment in patients with PD.

PMID- 19754408
TI  - Renoprotective potency of heme oxygenase-1 induction in rat renal ischemia
      reperfusion.
AB  - PURPOSE: Renal injury caused by ischemia-reperfusion (IR) can lead to acute renal
      failure or delayed graft function. Renal ischemia-reperfusion (RIR) induces
      inflammatory disorders via activation of arachidonic acid metabolism into
      prostaglandin E(2) (PGE(2)). Two inducible enzymes, COX-2 and microsomal
      prostaglandin E synthase (mPGES), regulate PGE(2) production. Heme oxygenase-1
      (HO-1) is a cytoprotective enzyme activated during cellular stress.
      Overexpression of HO-1 is beneficial in transplantation models including antigen
      independent IR injury, acute and chronic allograft rejection. MATERIALS AND
      METHODS: We investigated the effect of HO-1 induction on the COX pathway,
      antioxidant enzyme activities, malondialdehyde (MDA) levels, and apoptosis in rat
      kidneys subjected to 45 min ischemia and 1 h or 24 h reperfusion. Rats were
      injected intraperitoneally with either: 50 mg/kg hemin (HO-1 inducer groups: H1,
      H2); 50 micromol/kg ZnPP (HO-1 inhibitor groups: Hz1, Hz2); or 0.9% saline
      (control groups: r1, r2). Sham animals (Sh) did not undergo RIR. RESULTS: Serum
      creatinine increased significantly after RIR (r vs Sh; p <0.05). Hemin treatment
      induced a significant decrease in serum creatinine after RIR (H vs r; p <0.05)
      whereas ZnPP treatment significantly increased serum creatinine levels (Sh vs Hz;
      p <0.05). Hemin reduced the severity of acute tubular necrosis and significantly
      reduced COX-2 and mPGES expression (p <0.05). Hemin did not alter depleted
      antioxidant enzyme activity but did decrease levels of MDA (p <0.05). Hemin also
      reduced caspase-3 expression. CONCLUSIONS: HO-1 decreased the degree and severity
      of tubular damage after IR, probably by attenuating the cytotoxic effects of
      inflammatory infiltrates and apoptosis.

PMID- 19754409
TI  - General principles for the treatment of non-infectious uveitis.
AB  - Ocular inflammatory disorders constitute a sight-threatening group of diseases
      that might be managed according to their severity. Their treatment guidelines
      experience constant changes with new agents that improve the results obtained
      with former drugs. Nowadays we can make use of a five step protocol in which
      topical, periocular and systemic corticosteroids remain as the main therapy for
      non infectious uveitis. In addition, immunosuppresive drugs can be added in order
      to enhance the anti-inflammatory effects and to develop the role of
      corticosteroid-saving agents. These can be organized in four other steps:
      Cyclosporine and Methotrexate in a second one; Azathioprine, Mycophenolate
      Mofetil and Tacrolimus in a third step; biological anti-TNF drugs in fourth
      position; and a theoretical last one with Cyclophosphamide and Chlorambucil. In
      the present review we go through the main characteristics and complications of
      all these treatments and make a rational of this five-step treatment protocol for
      non infectious posterior uveitis.

PMID- 19754410
TI  - Anti-inflammatory drugs in psychiatry.
AB  - Nervous and immune system interact through many different messenger substances
      such as neurotransmitters, cytokines or neuropeptides. For instance,
      neuropeptides are capable of affecting the metabolism of cells belonging to the
      immune system. Conversely, cytokines such as tumor necrosis factor (TNF)-alpha,
      interferon (IFN)-alpha and IFN-gamma, contribute to the receptor resistance of
      neuropeptides, reduce the availability of amino acids which are needed for the
      synthesis of neurotransmitters or show neurotoxic effects. Other cytokines like
      granulocyte-colony stimulating factor (G-CSF) may be highly attractive candidates
      for the treatment of neurodegenerative conditions. Cytokines are decisively
      involved in the pathophysiology of psychiatric disorders such as depression,
      schizophrenia or anorexia nervosa as well as in neurological, respectively
      neurodegenerative diseases like Parkinson's or Alzheimer's. This connection
      between the immune system and the pathogenesis of psychiatric disorders leads to
      the concept that immunomodulatory drugs which are already in use for various
      diseases related to the immune system may also be efficient in the treatment of
      psychiatric disorders. This article is supposed to give an overview over the
      current concepts and possibilities since hopefully these hypotheses lead to new
      therapeutical strategies for psychiatric patients in the future.

PMID- 19754411
TI  - Possible roles of microglial cells for neurotoxicity in clinical
      neurodegenerative diseases and experimental animal models.
AB  - Microglia has been demonstrated to play critical roles in various
      neurodegenerative disorders, such as Parkinson's disease (PD), Alzheimer's
      disease (AD), Huntington's disease (HD) as well as neuroinflammatory disorders
      including AIDS encephalitis, multiple sclerosis. In this manuscript, we review
      the possible roles of microglial cells in animal models of these clinical
      disorders and human clinical cases. Activated microglia has been demonstrated in
      various brain regions, such as the hippocampus, substantia nigra and cortex in
      PD, AD and HD. The contribution of microglial cells to these neurodegenerative
      disorders is supported by findings in animal experiments: (1) microglial
      activation precedes the neurodegenerative changes; (2) activated microglia
      surround the region that undergo neurodegeneration and phagocytose the
      degenerating cells; (3) activated microglia release neurotoxic molecules such as
      interleukin(IL)-1beta, IL-6, TNF-alpha, nitric oxide, reactive oxygen species;
      (4) inhibition of microglial activation leads to the amelioration of
      neurodegeneration, (5) microglia derived from aged animal exert more toxicity to
      neurons in an age-dependent fashion, in the same way neurodegenerative disorders
      occur. Although roles of activated microglia in those clinical disorders needs to
      be further investigated, these findings suggest that microglial cells may
      contribute to the progression of neurodegenerative changes as well as
      inflammation in the brain. Thus, the treatment to target microglial inhibition
      may help to develop the pharmaceutical approaches for those clinical disorders.

PMID- 19754412
TI  - Leptin in non-autoimmune inflammation.
AB  - Leptin is an adipokine that modulates multiple functions including energy
      homeostasis, thermoregulation, bone metabolism, endocrine and pro-inflammatory
      immune responses. Several studies have implicated leptin in the pathogenesis of
      chronic autoimmune inflammatory conditions such as autoimmune encephalomyelitis,
      intestinal bowel inflammation and type-1 diabetes. This review focuses on the
      role of leptin in non-autoimmune inflammatory diseases that include renal, liver
      and lung inflammation, atherosclerosis and metabolic syndrome, Behcet's disease
      and endometriosis.

PMID- 19754413
TI  - Assessment of airway inflammation by exhaled breath condensate and impedance due
      to gastroesophageal reflux disease (GERD).
AB  - Avoiding oxidative stress in the airways is important for the treatment of
      respiratory disease associated with gastroesophageal reflux disease (GERD). It is
      often difficult to decide whether GERD is causing airway inflammation or whether
      an airway disease is complicated by GERD. Measurement of exhaled breath
      condensate (EBC) is performed by cooling and collecting the airway lining fluid
      contained in exhaled air. A decrease of pH and an increase of the 8-isoprostane
      concentration in EBC have been observed in patients with mild to moderate asthma
      accompanied by GERD. There are still problems to be overcome before EBC can be
      used clinically, but pH and 8-isoprostane may be promising objective markers of
      airway inflammation due to GERD. The disease concept and diagnosis of GERD are
      constantly advancing, including the development of impedance methods. It is
      expected that treatment will be based on the latest diagnostic knowledge of GERD
      associated with respiratory disease and on monitoring of airway inflammation.

PMID- 19754414
TI  - Targeting leukotrienes for the treatment of COPD?
AB  - New drugs and new approaches of the treatment of chronic obstructive pulmonary
      disease (COPD) are needed. Despite recent advances in medical therapeutics,
      treatment of patients with COPD remains largely symptomatic. Although inhaled
      corticosteroids are currently the drug of choice for anti-inflammatory therapy,
      the inflammatory process in COPD is essentially steroid resistant. By now, COPD
      has been increasingly recognized as an inflammatory disease characterized by
      sputum neutrophilia and, in some cases, eosinophilia. Moreover other cell types
      thought to play the predominant role in COPD, are cytotoxic T lymphocytes (CD8+
      T) cells and macrophages. Leukotriene B4, (LTB 4), a neutrophil and T cell
      chemoattractant which is produced by macrophages, neurophils and epithelial
      cells, is a potent inflammatory mediator. Also cysteinyl leukotrienes (LTC4, LTD4
      and LTE4) are known to induce mucus secretion, inflammatory cell infiltration,
      increase vascular permeability and tissue edema, damage ciliary clirens, and
      cause severe bronchoconstriction. These are derivatives of arachidonic acid,
      metabolized via 5-lypoxygenase (5-LO) pathway. There are several sites along this
      pathway that antileukotriene agents exert their action and at the end-organ
      receptors. They are classified into two major categories: receptor antagonists
      and synthesis inhibitors. Beneficial effects on therapy of patients with COPD
      have already derived from studies, while they seem well tolerated. More studies
      are underway.

PMID- 19754415
TI  - P53 family: at the crossroads in cancer therapy.
AB  - p53 and its related genes, p73 and p63, are members of the p53 gene family. While
      p53 is the most frequently mutated gene in human tumors, p73 and p63 are rarely
      mutated or lost in cancers. Although p53-deficient cancer cells are often less
      responsive to chemotherapy, they are not completely drug resistant, suggesting
      that other apoptotic pathways are at work. Interestingly, several studies have
      shown that p73, and more recently p63, are involved in cellular response to
      cancer therapy, while others have indicated that p63 and p73 are required for p53
      induced apoptosis, delineating functional interplay between p53 family members.
      The latest reports in this field have established that Nutlin-3, a selective
      inhibitor of p53-MDM2 interaction, disrupts p73-MDM2 and enhances p73 function in
      p53-null cells, and that a p53-derived peptide that targets iASPP--a common
      negative regulator of p53 family members--can trigger cell death via a p73
      dependent mechanism. It has also been shown that a small-molecule RETRA
      suppressed mutant p53-bearing cancers cells through a p73-dependent salvage
      pathway. Finally, there is increasing evidence that cleaved fragments of p53, p63
      and p73 are involved in apoptosis and it remains to be determined whether or not
      pro-forms of the p53 family play an apoptotic role mediated by cleavage. This
      review will highlight research into drugs and mechanisms that activate p63 and
      p73, since these proteins are not mutated in cancers and as such are potential
      candidates for replacing p53 in p53-deficient cells. It will therefore focus on
      recent findings in the search for pathways and molecules capable of modulating
      p53 family protein activities and restoring response to cancer therapy,
      particularly in tumors bearing p53 mutations.

PMID- 19754416
TI  - Fluorescent cisplatin analogues and cytotoxic activity.
AB  - Cisplatin is one of the chemotherapeutic agents used the most for testicular,
      ovarian and several other cancers. In order to overcome cisplatin resistance,
      other platinum (Pt) compounds have been developed and, in the last ten years, Pt
      derivatives with reporting activity have also been synthesized. The first
      generation of reporting Pt-compounds was based on linking a fluorescent molecule
      (e.g. cyanine) to cisplatin, but more recent studies have focused on strategies
      to synthesize intrinsically fluorescent derivatives. Accordingly, bile acid Pt
      compounds have shown fluorescence intensity that is stable at room temperature
      for a long time; this fluorescence is maintained after binding to
      oligonucleotides or DNA. Because of this, the binding mode of these compounds to
      DNA can be easily analyzed both by flow injection and fluorescence techniques,
      showing that although these compounds target the nuclei, they form adducts with
      the DNA that are different from those due to cisplatin. In line with this, these
      bile acid derivatives have shown increased cytotoxicity and ability to overcome
      resistance as compared to cisplatin in several cell lines. Moreover, in contrast
      to cisplatin, the activity of these compounds does not seem to be restricted to
      cycling cells but they also seem to kill resting cells. This review summarizes
      the information available on reporting Pt-compounds and focuses on these novel,
      intrinsically fluorescent bile acid Pt derivatives, their biochemical
      characteristics and biological activity.

PMID- 19754417
TI  - How to recognize and workaround pitfalls in QSAR studies: a critical review.
AB  - Quantitative Structure-Activity Relationships (QSAR) are based on the hypothesis
      that changes in molecular structure reflect proportional changes in the observed
      response or biological activity. In order to successfully conduct QSAR studies
      certain conditions have to be met that are not frequently reported in the
      literature. This suggests that some authors are not aware of the principle flaws,
      occasional shortcomings, and circumstantial downsides of QSAR methods. The
      present paper focuses on prerequisites to set up correct models and on
      limitations of model applications. Their implications are systematically
      described and illustrated as pitfalls that have strong implications in QSAR, and
      possible solutions are suggested. The paper is focused on small scale 2D- and 3D
      QSAR studies for lead optimization. The work is enriched with comprehensive
      comments and non-mathematical explanations for the computer practitioner in
      Medicinal Chemistry.

PMID- 19754418
TI  - Inhibitors of the microsomal prostaglandin E(2) synthase-1 as alternative to non
      steroidal anti-inflammatory drugs (NSAIDs)--a critical review.
AB  - Pharmacological suppression of cyclooxygenase (COX)-1 and -2-mediated prostanoid
      biosynthesis by non steroidal anti-inflammatory drugs (NSAIDs) is used in the
      therapy of inflammation, fever, and pain. However, long-term application of these
      drugs is associated with severe side effects, mainly gastrointestinal injury and
      renal irritations, apparently due to impaired biosynthesis of physiologically
      relevant prostanoids. Although COX-2 selective drugs (coxibs) show reduced
      gastrointestinal complications, recent clinical trials indicated a significantly
      increased cardiovascular risk. In order to minimize these side-effects, selective
      suppression of microsomal prostaglandin E(2) synthase (mPGES)-1 derived
      prostaglandin (PG)E(2) formation has been considered as alternative to general
      inhibition of prostanoid biosynthesis. mPGES-1 is functionally coupled to COX-2
      being responsible for excessive PGE(2) generation connected to pathologies and
      current knowledge suggests key roles of mPGES-1 in inflammation, pain, fever,
      atherosclerosis, and tumorigenesis. However, mPGES-1 as promising therapeutic
      target was questioned because blockade of mPGES-1 allows redirection of the
      substrate PGH(2) to other PG synthases, and the consequences are still elusive.
      This review summarizes current knowledge about synthetic and natural mPGES-1
      inhibitors focusing on structural and mechanistic investigations. Further, the
      therapeutic efficiency and safety is critically discussed on the basis of
      cellular and animal studies in which mPGES-1 activity was pharmacologically or
      genetically (knockout, knockdown) modulated.

PMID- 19754419
TI  - Direct covalent modification as a strategy to inhibit nuclear factor-kappa B.
AB  - Nuclear Factor-KkappaB (NF-kappaB) is a transcription factor whose inappropriate
      activation may result in the development of a number of diseases including
      cancer, inflammation, neurodegeneration and AIDS. Recent studies on NF-kappaB
      mediated pathologies, made therapeutic interventions leading to its inhibition an
      emerging theme in pharmaceutical research. NF-kappaB resides in the cytoplasm and
      is activated by several time-dependent factors, leading to proteasome-dependent
      degradation of its inhibitory protein (IkappaB), resulting in free NF-kappaB (p50
      and p65 subunits, involved in disease states), which binds to target DNA sites,
      further resulting in enhanced transcription of several disease associated
      proteins. The complex pathway of NF-kappaB, finally leading to its DNA binding,
      has attracted several approaches interfering with this pathway. One such approach
      is that of a direct covalent modification of NF-kappaB. In this article, we
      present a critical review on the pharmacological agents that have been studied as
      inhibitors of NF-kappaB by covalently modifying redox-regulated cysteine residues
      in its subunits, ultimately resulting in the inhibition of kappaB DNA recognition
      and binding. Beginning with a general overview of NF-kappaB pathway and several
      possibilities of chemical interventions, the significance of redox-regulation in
      NF-kappaB activation and DNA binding is presented. Further, protein S-thiolation,
      S-nitrosylation and irreversible covalent modification are described as regular
      biochemical events in the cell, having provided a guideline for the development
      of NF-kappaB inhibitors discussed further. Although just a handful of inhibitors,
      with most of them being alkylating agents have been studied in the present
      context, this approach presents potential for the development of a new class of
      NF-kappaB-inhibitors.

PMID- 19754420
TI  - The structure and pharmacological functions of coumarins and their derivatives.
AB  - Coumarins are of many different structures. They constitute an important class of
      pharmacological agents possessing a range of different physiological activities
      including anti-cancer, anti-oxidant, anti- inflammation, anti-HIV, anti
      coagulant, anti-bacterial, analgesic and comparative immune-modulation. Recently,
      coumarins have attracted intense research interest. Of great interest is the
      possibility that this class of molecules could be a source of drugs for the
      therapy of several diseases. These include recent insights into inhibiting cell
      proliferation by interfering with mitotic spindle microtubule function, decrease
      Matrix Metalloproteinase (MMP) activity, block the cell cycle in the S or G2/M
      phases to interfere with processes of cell division, suppress O2(-) generation in
      leukocytes, inhibit different protein kinases, modulate the signalings, induce
      carcinogen-detoxifying enzymes glutathione S-transferases (GSTs) and/or NAD(P)H
      quinine oxidoreductase (NQO1), suppress the phosphorylation of Akt/PKB as a
      mechanism inhibiting inflammation, progress in structure modification to increase
      in anti-fungal action, to broaden against bacteria spectrum, to enhance
      inhibiting activities of nitric oxide synthase (NOS) and cyclooxygenase (COX), to
      strengthen anti-oxidant activity and to exhibite a much higher cytotoxicity
      against human umbilical vein endothelial cell (HUVEC). With fewer non-hemorrhagic
      side effects than the indanedione derivatives, they can be applied as an oral
      anticoagulant commonly for preventing venous thromboembolism following orthopedic
      surgery, recurrent myocardial infarction and the treatment of systemic embolism
      in atrial fibrillation, together with the significant advances in the basis of
      drug action. It is therefore useful to build up some correlations with the data
      available in order to better explore the molecular and cellular mechanism of
      coumarin action in the treatment of diseases. This review will focus on recent
      advances in molecular and cellular mechanisms of coumarin action involved with
      the relationship between structure and activity.

PMID- 19754421
TI  - CRH-like peptides in human reproduction.
AB  - CRH and Urocortins 1, 2 and 3 comprise the, so far identified, members of the CRH
      family of peptides in humans. Their actions are mediated through two distinct
      receptors, CRHR1 and CRHR2, encoded by different genes. CRH-like peptides and
      their receptors have been identified in reproductive tissues, such as the ovary,
      uterus as well as fetal and placental membranes. The participation of the "CRH
      family" of peptides and receptors in the physiology of these organs is currently
      under intense investigation. During the estrus cycle, endometrial CRH acts as a
      fine tuner of stromal cells decidualization. CRH is produced by embryonic
      trophoblast and maternal decidual cells and plays important roles in
      implantation. CRH also participates in the control of trophoblast invasion.
      Furthermore, placental CRH and Urocortin are involved in the mechanisms
      controlling maintenance of pregnancy and the onset of labor. The level of
      participation of urocortins 2 and 3 in these phenomena is currently under
      investigation. This review will focus on existing data on the expression and
      regulation of the CRH family of peptides and their receptors in the female
      reproductive system, as well as in their potential biologic role(s) in human
      reproductive functions.

PMID- 19754422
TI  - In search for the troponin of the kidney.
AB  - The prevalence of chronic renal disease is increasing dramatically in
      industrialized nations. Recent surveys in Europe and the US show that about 10%
      of the total population are affected. Patients with end stage disease,
      necessitating dialysis or transplantation, are only the tip of the iceberg. Even
      with treatment these subjects suffer from a massive reduction in quality and
      quantity of life despite consuming a large proportion of healthcare expenditures.
      As quite effective treatment strategies are available to prevent progression
      there is a pressing clinical need for early detection, differential diagnosis and
      assessment of the individual prognosis of renal disease. The current gold
      standard is the measurement of serum creatinine; despite the fact this method has
      some major limitations. These can be partially overcome by the use of newer
      markers like Cystatin C. However, a major problem using this approach is the fact
      that serum creatinine and Cystatin C are markers of renal excretory function only
      and hence no differential diagnosis can be derived from them. Furthermore a
      single measurement is not sufficient to estimate the prognosis of an individual
      patient, especially in the early stages of the disease, making tailored treatment
      difficult. In this review we will summarize our current knowledge about the
      markers in use today and also provide information on new, potentially superior
      markers, which would enable a much more complete non-invasive assessment of a
      growing patient population.

PMID- 19754423
TI  - Synthetic and natural compounds that interact with human cytochrome P450 1A2 and
      implications in drug development.
AB  - Human cytochrome P450 1A2 (CYP1A2) is one of the major CYPs in the liver (
      approximately 13%) and metabolizes about 20% of clinically used drugs. CYP1A2 is
      a 515-residue protein with a molecular mass of 58,294 Dal. The recently published
      crystal structure of CYP1A2 in complex with alpha-naphthoflavone has showed a
      rather compact active site with a relatively small volume of the cavity of 375
      A(3), which is 44.2% and 49.3% larger than that of CYP2A6 (260 A(3)) and CYP2E1
      (190 A(3)), respectively. A series of residues in the substrate recognition
      regions of CYP1A2 (e.g. Arg108, Thr124, Thr223, Glu225, Phe226, Lys250, Arg251,
      Lys253, Asn312, Asp313, Glu318, Thr319, Asp320, Thr321, Val322, Leu382, Thr385,
      and Ile386) have been shown to play important roles in ligand-enzyme binding
      based on site-directed mutagenesis and homology modeling studies. Typical CYP1A2
      substrates generally contain planar ring that can fit the narrow and planar
      active site of the enzyme, such as propranolol, clozapine, guanabenz, flutamide,
      imatinib, thalidomide, carbamazepine, lidocaine, theophylline, tacrine,
      tizanidine, zolpidem, riluzole, zileuton, and leflunomide. CYP1A2 is one of the
      major enzymes that bioactivate a number of procarcinogens including polycyclic
      aromatic hydrocarbons (e.g., benzo[a]pyrene), heterocyclic aromatic amines/amides
      (e.g. 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine), mycotoxins (e.g.
      aflatoxin B(1)) and some natural compounds such as aristolochic acids present in
      several Chinese herbal medicines. This enzyme also metabolizes several important
      endogenous compounds including retinols, melatonin, steroids, uroporphyrinogen
      and arachidonic acids. Like many of other CYPs, CYP1A2 is subject to induction
      and inhibition by a number of compounds. In particular, several therapeutic drugs
      including antofloxacin, carbamazepine, dihydralazine, furafylline, isoniazid,
      rofecoxib, clorgyline, thiabendazole, and zileuton are mechanism-based inhibitors
      of CYP1A2. Reversible and irreversible inhibition of by drugs CYP1A2 may provide
      an explanation for some clinical drug-drug interactions. Similar to CYP1A1 and
      1B1, CYP1A2 is primarily regulated by the aromatic hydrocarbon receptor (AhR), a
      ligand-activated transcription factor and a basic helix-loop-helix protein
      belonging to the Per-Arnt-Sim family of transcription factors. CYP1A2 is
      polymorphic and a number of genetic mutations in CYP1A2 have been reported. It
      has been suggested that approximately 35 to 75% of the interindividual
      variability in CYP1A2 activity is due to genetic factors. Some of the mutations
      of CYP1A2 have been found to alter the clearance of drugs that are extensively
      metabolized by CYP1A2. Collectively, CYP1A2 plays a major role in drug
      metabolism, procarcinogen activation and some drug-drug interactions; it is
      important to identify whether a new drug is a substrate, inducer or inhibitor in
      drug development. This candidate selection might eventually lead to a less
      prominent role of this enzyme in the future for drug metabolism and minimize the
      potential for significant polymorphic metabolism in humans and drug-drug
      interactions when used in combination with CYP1A2 inhibitors.

PMID- 19754424
TI  - Apoptosis and human diseases: mitochondrion damage and lethal role of released
      cytochrome C as proapoptotic protein.
AB  - Apoptosis is strictly connected to the pathogenesis of many human diseases,
      including neoplastic, neurodegenerative or cardiovascular diseases. It is a
      highly programmed cell death which can be activated by various factors.
      Mitochondria play a key role in the apoptotic process; their damage, which
      involves permeabilization of the outer mitochondrial membrane, activates a series
      of events that lead to cell death. Of the two proposed signaling pathways of
      apoptosis, i.e. the 'extrinsic' and the 'intrinsic' pathway, the latter is
      assumed to initiate in mitochondria. Its activation involves release of
      cytochrome c and other pro-apoptotic factors from the mitochondrial intermembrane
      space. In the cytosol, cytochrome c exerts its pro-apoptotic action. It binds to
      the apoptosis protease activation factor (APAf-1) and forms a complex indicated
      as 'apoptosome'. The complex-induced activation of pro-caspase 9 initiates an
      enzymatic reaction cascade leading to the execution of apoptosis in cells. This
      review provides an overview of the key role played by mitochondria and cytochrome
      c in the activation of the apoptotic process.

PMID- 19754425
TI  - Extraction of structure-activity relationship information from high-throughput
      screening data.
AB  - The wealth of biological screening data that is generated poses substantial
      problems to medicinal chemistry. A key question becomes how to best prioritize
      and select hits for further evaluation from the many weakly active compounds that
      are typically identified in HTS campaigns. Such decisions can be substantially
      supported if it is possible to evaluate preliminary structure-activity
      relationship (SAR) information that might be contained in screening data. If SAR
      information can be extracted from screening data, one can attempt to estimate the
      chemical optimization potential of hits. We will discuss different types of
      approaches that have been developed to facilitate HTS data analysis, with special
      emphasis on recent methods to explore SAR information contained in screening
      sets.

PMID- 19754426
TI  - Bifunctional cytosolic UDP-glucose 4-epimerases catalyse the interconversion
      between UDP-D-xylose and UDP-L-arabinose in plants.
AB  - UDP-sugars serve as substrates in the synthesis of cell wall polysaccharides and
      are themselves generated through sequential interconversion reactions from UDP
      Glc (UDP-glucose) as the starting substrate in the cytosol and the Golgi
      apparatus. For the present study, a soluble enzyme with UDP-Xyl (UDP-xylose) 4
      epimerase activity was purified approx. 300-fold from pea (Pisum sativum L.)
      sprouts by conventional chromatography. The N-terminal amino acid sequence of the
      enzyme revealed that it is encoded by a predicted UDP-Glc 4-epimerase gene,
      PsUGE1, and is distinct from the UDP-Xyl 4-epimerase localized in the Golgi
      apparatus. rPsUGE1 (recombinant P. sativum UGE1) expressed in Escherichia coli
      exhibited both UDP-Xyl 4-epimerase and UDP-Glc 4-epimerase activities with
      apparent Km values of 0.31, 0.29, 0.16 and 0.15 mM for UDP-Glc, UDP-Gal (UDP
      galactose), UDP-Ara (UDP-L-arabinose) and UDP-Xyl respectively. The apparent
      equilibrium constant for UDP-Ara formation from UDP-Xyl was 0.89, whereas that
      for UDP-Gal formation from UDP-Glc was 0.24. Phylogenetic analysis revealed that
      PsUGE1 forms a group with Arabidopsis UDP-Glc 4-epimerases, AtUGE1 and AtUGE3,
      apart from a group including AtUGE2, AtUGE4 and AtUGE5. Similar to rPsUGE1,
      recombinant AtUGE1 and AtUGE3 expressed in E. coli showed high UDP-Xyl 4
      epimerase activity in addition to their UDP-Glc 4-epimerase activity. Our results
      suggest that PsUGE1 and its close homologues catalyse the interconversion between
      UDP-Xyl and UDP-Ara as the last step in the cytosolic de novo pathway for UDP-Ara
      generation. Alternatively, the net flux of metabolites may be from UDP-Ara to UDP
      Xyl as part of the salvage pathway for Ara.

PMID- 19754427
TI  - IRAK1-independent pathways required for the interleukin-1-stimulated activation
      of the Tpl2 catalytic subunit and its dissociation from ABIN2.
AB  - The protein kinase Tpl2 (tumour progression locus 2) is activated by LPS
      (lipopolysaccharide), TNFalpha (tumour necrosis factor alpha) and IL
      (interleukin)-1. Activation of the native Tpl2 complex by these agonists requires
      the IKKbeta {IkappaB [inhibitor of NF-kappaB (nuclear factor kappaB)] kinase
      beta}-catalysed phosphorylation of the p105/NF-kappaB1 subunit and is accompanied
      by the release of the catalytic subunit from both p105/NF-kappaB1 and another
      subunit ABIN2 (A20-binding inhibitor of NF-kappaB 2). In the present study we
      report that IL-1 activates the transfected Tpl2 catalytic subunit in an HEK
      (human embryonic kidney)-293 cell line that stably expresses the IL-1R (IL-1
      receptor), but does not express the protein kinase IRAK1 (IL-1R-associated
      kinase). In these cells IL-1 does not activate IKKbeta or induce the
      phosphorylation of p105/NF-kappaB1, and nor does the IKKbeta inhibitor PS1145
      prevent the IL-1-induced activation of transfected Tpl2. However, the IL-1
      stimulated activation of transfected Tpl2 in IRAK1-null cells or activation of
      the endogenous Tpl2 complex in IRAK1-expressing cells is suppressed by the
      protein kinase inhibitor PP2 by a mechanism that does not involve inhibition of
      Src family protein tyrosine kinases. The IL-1-stimulated activation of
      transfected Tpl2 is accompanied by its phosphorylation at Thr290 and Ser400 and
      by enhanced phosphorylation of Ser62, which we demonstrate are
      autophosphorylation events catalysed by Tpl2 itself. We further show that IL-1
      triggers the dissociation of Tpl2 from co-transfected ABIN2 in IRAK1-null IL-1R
      cells, which is not suppressed by PP2 or by the inhibition of Tpl2 or IKKbeta.
      These studies identify two new signalling events involved in activation of the
      native Tpl2 complex by IL-1. First, the IRAK1-, IKKbeta- and PP2-independent
      dissociation of Tpl2 from ABIN2; secondly, the IRAK1- and IKKbeta-independent,
      but PP2-sensitive, activation of the Tpl2 catalytic subunit.

PMID- 19754428
TI  - Structural insight on the control of urea synthesis: identification of the
      binding site for N-acetyl-L-glutamate, the essential allosteric activator of
      mitochondrial carbamoyl phosphate synthetase.
AB  - NAG (N-acetyl-L-glutamate), the essential allosteric activator of the first urea
      cycle enzyme, CPSI (carbamoyl phosphate synthetase I), is a key regulator of this
      crucial cycle for ammonia detoxification in animals (including humans). Automated
      cavity searching and flexible docking have allowed identification of the NAG site
      in the crystal structure of human CPSI C-terminal domain. The site, a pocket
      lined by invariant residues and located between the central beta-sheet and two
      alpha-helices, opens at the beta-sheet C-edge and is roofed by a three-residue
      lid. It can tightly accommodate one extended NAG molecule having the delta-COO-
      at the pocket entry, the alpha-COO- and acetamido groups tightly hydrogen bonded
      to the pocket, and the terminal methyl of the acetamido substituent surrounded by
      hydrophobic residues. This binding mode is supported by the observation of
      reduced NAG affinity upon mutation of NAG-interacting residues of CPSI
      (recombinantly expressed using baculovirus/insect cells); by the fine-mapping of
      the N-chloroacetyl-L-glutamate photoaffinity labelling site of CPSI; and by
      previously established structure-activity relationships for NAG analogues. The
      location of the NAG site is identical to that of the weak bacterial CPS activator
      IMP (inosine monophosphate) in Escherichia coli CPS, indicating a common origin
      for these sites and excluding any relatedness to the binding site of the other
      bacterial CPS activator, ornithine. Our findings open the way to the
      identification of CPSI deficiency patients carrying NAG site mutations, and to
      the possibility of tailoring the activator to fit a given NAG site mutation, as
      exemplified here with N-acetyl-L(+/-)-beta-phenylglutamate for the W1410K CPSI
      mutation.

PMID- 19754429
TI  - miRNPs: versatile regulators of gene expression in vertebrate cells.
AB  - TNFalpha (tumour necrosis factor alpha) mRNA bears in its 3'-UTR (untranslated
      region) a conserved ARE (AU-rich element), a signal that exerts tight post
      transcriptional control over the expression of TNFalpha and other cytokines. We
      found that the TNFalpha ARE increases translational efficiency when cell growth
      is arrested, a physiologically relevant state occurring during inflammation,
      angiogenesis and monocyte differentiation. Under these conditions, called
      quiescence, the miRNP (microribonucleoprotein)-associated proteins FXR1 (Fragile
      X mental retardation-related protein 1) and AGO2 (Argonaute 2), which are usually
      considered negative regulators, are transformed into effector molecules that bind
      the ARE to activate translation. We then identified a specific miRNA (microRNA)
      that directs the association of AGO2 and FXR1 with the ARE during translational
      up-regulation. Two other well-characterized miRNAs likewise promote translation
      activation in quiescent or in contact-inhibited cells; yet, they repress
      translation in proliferating cells in the late S/G(2)-phase. We conclude that
      translational regulation by miRNPs oscillates between repression and activation
      as a function of the cell cycle. The activating role of miRNAs is now being
      confirmed in the immature Xenopus oocyte, which mimics the quiescent state.

PMID- 19754430
TI  - The emerging complexity of protein ubiquitination.
AB  - Protein ubiquitination and protein phosphorylation are two fundamental regulatory
      post-translational modifications controlling intracellular signalling events.
      However, the ubiquitin system is vastly more complex compared with
      phosphorylation. This is due to the ability of ubiquitin to form polymers, i.e.
      ubiquitin chains, of at least eight different linkages. The linkage type of the
      ubiquitin chain determines whether a modified protein is degraded by the
      proteasome or serves to attract proteins to initiate signalling cascades or be
      internalized. The present review focuses on the emerging complexity of the
      ubiquitin system. I review what is known about individual chain types, and
      highlight recent advances that explain how the ubiquitin system achieves its
      intrinsic specificity. There is much to be learnt from the better-studied
      phosphorylation system, and many key regulatory mechanisms underlying control by
      protein phosphorylation may be similarly employed within the ubiquitin system.
      For example, ubiquitination may have important allosteric roles in protein
      regulation that are currently not appreciated.

PMID- 19754431
TI  - Lipid rafts as functional heterogeneity in cell membranes.
AB  - Biological membranes are not structurally passive solvents of amphipathic
      proteins and lipids. Rather, it appears their constituents have evolved intrinsic
      characteristics that make homogeneous distribution of components unlikely. As a
      case in point, the concept of lipid rafts has received considerable attention
      from biologists and biophysicists since the formalization of the hypothesis more
      than 10 years ago. Today, it is clear that sphingolipid and cholesterol can self
      associate into micron-scaled phases in model membranes and that these lipids are
      involved in the formation of highly dynamic nanoscale heterogeneity in the plasma
      membrane of living cells. However, it remains unclear whether these entities are
      manifestations of the same principle. A powerful means by which the molecular
      organization of rafts can be assessed is through analysis of their functionalized
      condition. Raft heterogeneity can be activated to coalesce and laterally
      reorganize/stabilize bioactivity in cell membranes. Evaluation of this property
      suggests that functional raft heterogeneity arises through principles of lipid
      driven phase segregation coupled to additional chemical specificities, probably
      involving proteins.

PMID- 19754432
TI  - How and why does the endoplasmic reticulum move?
AB  - The ER (endoplasmic reticulum) is a fascinating organelle that is highly dynamic,
      undergoing constant movement and reorganization. It has many key roles, including
      protein synthesis, folding and trafficking, calcium homoeostasis and lipid
      synthesis. It can expand in size when needed, and the balance between tubular and
      lamellar regions can be altered. The distribution and organization of the ER
      depends on both motile and static interactions with microtubules and the actin
      cytoskeleton. In the present paper, we review how the ER moves, and consider why
      this movement may be important for ER and cellular function.

PMID- 19754433
TI  - Potential roles of myosin VI in cell motility.
AB  - There is now increasing evidence that myosin motor proteins, together with the
      dynamic actin filament machinery and associated adhesion proteins, play crucial
      roles in the events leading to motility at the leading edge of migrating cells.
      Myosins exist as a large superfamily of diverse ATP-dependent motors, and in the
      present review, we focus on the unique minus-end-directed myosin VI, briefly
      discussing its potential functions in cell motility.

PMID- 19754434
TI  - Dividing the goods: co-ordination of chromosome biorientation and mitotic
      checkpoint signalling by mitotic kinases.
AB  - Error-free chromosome segregation during cell division relies on chromosome
      biorientation and mitotic checkpoint activity. A group of unrelated kinases
      controls various aspects of both processes. The present short review outlines our
      current understanding of the roles of these kinases in maintaining chromosomal
      stability.

PMID- 19754435
TI  - Regulation of kinetochore-microtubule attachments by Aurora B kinase.
AB  - Accurate segregation of chromosomes in mitosis requires that spindle microtubules
      attach sister kinetochores to opposite poles of the mitotic spindle
      (biorientation). To achieve biorientation of all chromosomes, incorrect
      attachments are selectively destabilized, providing a fresh opportunity to
      biorient, whereas correct attachments are stabilized. Tension across the
      centromere may be the signal that distinguishes different attachment states, as
      spindle microtubules pull bioriented sister kinetochores in the opposite
      direction. Destabilization of incorrect attachments requires the Ipl1/Aurora B
      kinase, which phosphorylates kinetochore substrates that directly interact with
      microtubules. The present review focuses on how Aurora B regulates attachments in
      response to centromere tension.

PMID- 19754436
TI  - The assembly of lipid droplets and its relation to cellular insulin sensitivity.
AB  - The assembly of lipid droplets is dependent on PtdIns(4,5)P(2) that activates
      PLD(1) (phospholipase D(1)), which is important for the assembly process. ERK2
      (extracellular-signal-regulated kinase 2) phosphorylates the motor protein dynein
      and sorts it to lipid droplets, allowing them to be transported on microtubules.
      Lipid droplets grow in size by fusion, which is dependent on dynein and the
      transfer on microtubules, and is catalysed by the SNARE (soluble N-ethylmaleimide
      sensitive fusion protein-attachment protein receptor) proteins SNAP-23 (23 kDa
      synaptosome-associated protein), syntaxin-5 and VAMP-4 (vesicle-associated
      protein 4). SNAP-23 is also involved in the insulin-dependent translocation of
      the glucose transporter GLUT4 to the plasma membrane. Fatty acids induce a
      missorting of SNAP-23, from the plasma membrane to the interior of the cell,
      resulting in cellular insulin resistance that can be overcome by increasing the
      levels of SNAP-23. The same missorting of SNAP-23 occurs in vivo in skeletal
      muscle biopsies from patients with T2D (Type 2 diabetes). Moreover, there was a
      linear relation between the amount of SNAP-23 in the plasma membrane from human
      skeletal-muscles biopsies and the systemic insulin-sensitivity. Syntaxin-5 is low
      in T2D patients, which leads to a decrease in the insulin-dependent
      phosphorylation of Akt (also known as protein kinase B). Thus both SNAP-23 and
      syntaxin-5 are highly involved in the development of insulin resistance.

PMID- 19754437
TI  - Hepatitis C virus: viral proteins on the move.
AB  - There is now increasing evidence that LDs (lipid droplets) play a central role in
      the production of infectious HCV (hepatitis C virus) and participate in virus
      assembly. Two viral proteins, namely core, which forms the capsid, and NS5A (non
      structural 5A protein), a component of complexes engaged in viral RNA synthesis,
      are detected at LD surfaces in infected cells. Interactions between the two
      proteins may be critical for anchoring RNA replication sites to droplets for
      initiating virus assembly. The requirements for targeting of core in particular
      has received considerable attention since the nature of its interaction with LDs
      could play a key role in determining the efficiency of virion production. As well
      as attaching to droplets, core is able to alter their intracellular distribution
      and direct them towards the microtubule organizing centre. Inhibitors that
      disrupt microtubules block this redistribution by core and there is a concomitant
      decrease in virus production. Therefore altered dynamics of LDs may contribute to
      HCV assembly and release. The purpose of targeting LDs by HCV may be linked to
      their contribution to the formation of VLDLs (very-low-density lipoproteins) in
      hepatocytes since virus circulating in infected patients is associated with
      lipoprotein. Thus HCV may utilize the role played by LDs in the formation of
      lipoprotein particles as part of its life cycle and access this pathway by direct
      interaction of viral components with these intracellular storage organelles.

PMID- 19754438
TI  - Fat on the move: intracellular motion of lipid droplets.
AB  - Lipid droplets are intracellular organelles that play central roles in lipid
      metabolism. In many cells, lipid droplets undergo active motion, typically along
      microtubules. This motion has been proposed to aid growth and breakdown of
      droplets, to allow net transfer of nutrients from sites of synthesis to sites of
      need and to deliver proteins and lipophilic signals. This review summarizes the
      current understanding of where, why and how lipid droplets move.

PMID- 19754439
TI  - Structural basis of EB1 effects on microtubule dynamics.
AB  - +TIPs (plus-end tracking proteins) are an increasing group of molecules that
      localize preferentially to the end of growing microtubules. +TIPs regulate
      microtubule dynamics and contribute to the organization of the microtubular
      network within the cell. Thus they participate in a wide range of cellular
      processes including cell division, motility and morphogenesis. EB1 (end-binding
      1) is a highly conserved key member of the +TIP group that has been shown to
      modulate microtubule dynamics both in vitro and in cells. EB1 is involved in
      accurate chromosome segregation during mitosis and in the polarization of the
      microtubule cytoskeleton in migrating cells. Here, we review recent in vitro
      studies that have started to reveal a regulating activity of EB1, and its yeast
      orthologue Mal3p, on microtubule structure. In particular, we examine how EB1
      mediated changes in the microtubule architecture may explain its effects on
      microtubule dynamics.

PMID- 19754440
TI  - The role of TOG domains in microtubule plus end dynamics.
AB  - The XMAP215 (Xenopus microtubule-associated protein 215) and CLASP [CLIP-170
      (cytoskeletal linker protein 170) associated protein] microtubule plus end
      tracking families play central roles in the regulation of interphase microtubule
      dynamics and the proper formation of mitotic spindle architecture and flux.
      XMAP215 members comprise N-terminally-arrayed hexa-HEAT (huntingtin, elongation
      factor 3, the PR65/A subunit of protein phosphatase 2A and the lipid kinase Tor)
      repeats known as TOG (tumour overexpressed gene) domains. Higher eukaryotic
      XMAP215 members are monomeric and have five TOG domains. Yeast counterparts are
      dimeric and have two TOG domains. Structure determination of the TOG domain
      reveals that the six HEAT repeats are aligned to form an oblong scaffold. The TOG
      domain face composed of intra-HEAT loops forms a contiguous, conserved tubulin
      binding surface. Nested within the conserved intra-HEAT loop 1 is an invariant,
      signature, surface-exposed tryptophan residue that is a prime determinant in the
      TOG domain-tubulin interaction. The arrayed organization of TOG domains is
      critical for the processive mechanism of XMAP215, indicative that multiple
      tubulin/microtubule-binding sites are required for plus end tracking activity.
      The CLASP family has been annotated as containing a single N-terminal TOG domain.
      Using XMAP215 TOG domain structure determinants as a metric to analyse CLASP
      sequence, it is anticipated that CLASP contains two additional cryptic TOGL (TOG
      like) domains. The presence of additional TOGL domains implicates CLASP as an
      ancient XMAP215 relative that uses a similar, multi-TOG-based mechanism to
      processively track microtubule ends.

PMID- 19754441
TI  - Regulation of microtubule dynamic instability.
AB  - Proper regulation of MT (microtubule) dynamics is essential for various vital
      processes, including the segregation of chromosomes, directional cell migration
      and differentiation. MT assembly and disassembly is modulated by a complex
      network of intracellular factors that co-operate or antagonize each other, are
      highly regulated in space and time and are thus attuned to the cell cycle and
      differentiation processes. While we only begin to appreciate how the concerted
      action of MT stabilizers and destabilizers shapes different MT patterns, a clear
      picture of how individual factors affect the MT structure is emerging. In this
      paper, we review the current knowledge about proteins that modulate MT dynamic
      instability.

PMID- 19754442
TI  - Microsignalosomes: spatially resolved receptor signalling.
AB  - B-cells are a critical component of the adaptive immune system. As such, B-cells
      survey the body and mount appropriate protective responses to pathogen-derived
      antigens, resulting in the production of specific antibodies and induction of
      immunological memory. Given the effectiveness of these responses in selectively
      eliminating pathogenic infections, it is clear that the processes underlying
      antigen-induced B-cell activation must be highly regulated. Somewhat surprisingly
      given the specialized function of these immune cells, the BCR (B-cell receptor)
      functions similarly to receptors of the tyrosine kinase family that are
      commonplace in biology, as BCR ligation with antigen leads to B-cell
      proliferation and differentiation. In the Lymphocyte Interaction Laboratory, we
      are particularly interested in characterizing the very early molecular events
      underlying B-cell activation using a combination of cutting-edge high-resolution
      and in vivo imaging techniques.

PMID- 19754443
TI  - The delivery of endocytosed cargo to lysosomes.
AB  - In mammalian cells, endocytosed cargo that is internalized through clathrin
      coated pits/vesicles passes through early endosomes and then to late endosomes,
      before delivery to lysosomes for degradation by proteases. Late endosomes are
      MVBs (multivesicular bodies) with ubiquitinated membrane proteins destined for
      lysosomal degradation being sorted into their luminal vesicles by the ESCRT
      (endosomal sorting complex required for transport) machinery. Cargo is delivered
      from late endosomes to lysosomes by kissing and direct fusion. These processes
      have been studied in live cell experiments and a cell-free system. Late endosome
      lysosome fusion is preceded by tethering that probably requires mammalian
      orthologues of the yeast HOPS (homotypic fusion and vacuole protein sorting)
      complex. Heterotypic late endosome-lysosome membrane fusion is mediated by a
      trans-SNARE (soluble N-ethylmaleimide-sensitive factor-attachment protein
      receptor) complex comprising Syntaxin7, Vti1b, Syntaxin8 and VAMP7 (vesicle
      associated membrane protein 7). This differs from the trans-SNARE complex
      required for homotypic late endosome fusion in which VAMP8 replaces VAMP7. VAMP7
      is also required for lysosome fusion with the plasma membrane and its retrieval
      from the plasma membrane to lysosomes is mediated by its folded N-terminal longin
      domain. Co-ordinated interaction of the ESCRT, HOPS and SNARE complexes is
      required for cargo delivery to lysosomes.

PMID- 19754444
TI  - Dissecting dynamin's role in clathrin-mediated endocytosis.
AB  - The GTPase dynamin is essential for CME (clathrin-mediated endocytosis), but its
      exact function and mechanism of action have been controversial. Here, we review
      findings that have led to the current models for dynamin function, either as a
      mechanochemical enzyme driving membrane fission or as a regulatory GTPase
      monitoring rate-limiting steps in CME. However, these models are not mutually
      exclusive and subsequent studies have provided evidence for both dynamin
      functions. Recent evidence derived from divergent in vivo and in vitro approaches
      suggests that dynamin plays a dual role in CME, functioning at early stages as a
      fidelity monitor to regulate clathrin-coated pit maturation and at later stages
      to directly catalyse membrane fission and clathrin-coated vesicle formation.

PMID- 19754445
TI  - Rab7 and the CMT2B disease.
AB  - The CMT2B (Charcot-Marie-Tooth type 2B) disease is an autosomal dominant axonal
      neuropathy. Sensory loss, distal muscle weakness and wasting, frequent foot
      ulcers and amputations of the toes due to frequent infections characterize this
      neuropathy. Four missense mutations in the rab7 gene have been identified as
      causative of the disease. Rab7 is a small G-protein of the Rab family that
      controls vesicular transport to late endosomes and lysosomes in the endocytic
      pathway. The CMT2B-associated mutant Rab7 proteins show altered nucleotide
      dissociation rates and impaired GTPase activity. In addition, these mutant
      proteins are predominantly in the GTP-bound form when expressed in human cells
      and they are able to rescue Rab7 function in Rab7-depleted cells. Thus these
      mutations generate activated forms of Rab7 that are responsible for the
      development of the disease. In spite of these results, there are still important
      gaps in our understanding of the mechanism underlying CMT2B. Indeed, how these
      mutations in the rab7 gene affect specifically peripheral neurons leading to an
      axonal pathology in CMT2B is not clear, and it is a particularly puzzling and
      challenging issue in view of the fact that Rab7 is a ubiquitous protein. The
      present review discusses possible molecular mechanisms underlying CMT2B.

PMID- 19754446
TI  - The dynamic Rab11-FIPs.
AB  - The Rab11-FIPs (Rab11-family interacting proteins; also known as FIPs) constitute
      an evolutionarily conserved protein family that act as effector molecules for
      multiple Rab and Arf (ADP-ribosylation factor) GTPases. They were initially
      characterized by their ability to bind Rab11 subfamily members via a highly
      conserved C-terminal RBD (Rab11-binding domain). Resolution of the crystal
      structure of Rab11 in complex with FIPs revealed that the RBD mediates
      homodimerization of the FIP molecules, creating two symmetrical interfaces for
      Rab11 binding and leading to the formation of a heterotetrameric complex between
      two FIP and two Rab11 molecules. The FIP proteins are encoded by five genes and
      alternative splicing has been reported. Based on primary structure, the FIPs were
      subcategorized into two classes: class I [Rip11, FIP2 and RCP (Rab-coupling
      protein)] and class II (FIP3 and FIP4). Recent studies have identified the FIPs
      as key players in the regulation of multiple distinct membrane trafficking
      events. In this mini-review, we summarize the Rab11-FIP field and discuss, at
      molecular and cellular levels, the recent findings on FIP function.

PMID- 19754447
TI  - Structural aspects of Rab6-effector complexes.
AB  - The small GTPase Rab6 regulates vesicle trafficking at the level of Golgi.
      Recently, the crystal structures of Rab6 in complexes with two unrelated
      effectors have been determined. The structure of Rab6a-GTP in complex with a 378
      residue internal fragment of the effector Rab6IP1 (Rab6-interacting protein 1)
      has been solved. In addition, the structure of Rab6 with the golgin, GCC185, has
      also been determined. In both complexes, two alpha-helices from the effector
      mediate binding to switch I, switch II and the interswitch region of Rab6.
      Comparisons of the complexes reveal significant conformational changes in the
      conserved hydrophobic triad of Rab6. Thus conformational flexibility in the triad
      mediates recognition of compositionally distinct alpha-helical coiled coils,
      providing a rationale for the promiscuity of Rab6 in effector recruitment.

PMID- 19754448
TI  - The 'super-resolution' revolution.
AB  - We are currently in the midst of an exciting revolution in microscopy. In many
      ways, this has been happening for several decades, but it is the rate of
      development of new methods that has increased recently. The last few years have
      seen an impressive proliferation of new instruments for imaging at higher
      resolution, imaging single molecules and faster and more sensitive
      multidimensional live cell imaging. These include light sheet microscopy,
      stimulated emission depletion, structured illumination and live cell imaging on
      the OMX (optical microscopy experimental) platform. However, new probes and image
      analysis methods have also been crucial for the development of these
      revolutionary methods.

PMID- 19754449
TI  - Walking, hopping, diffusing and braking modes of kinesin-5.
AB  - It is clear that the main cellular mission of the molecular motor kinesin-5
      (known as Eg5 in vertebrates) is to cross-link antiparallel microtubules and to
      slide them apart, thus playing a critical role during bipolar spindle formation.
      Nonetheless, important questions about the cell biological and biophysical
      mechanisms of Eg5 remain unanswered. With the 20th 'birthday' of Eg5 approaching,
      we discuss recent insights into the in vitro and in vivo functions of Eg5, in the
      context of our own recent work.

PMID- 19754450
TI  - A novel function of lipid droplets in regulating longevity.
AB  - Growing evidence supports the view that LDs (lipid droplets) are dynamic
      organelles that can serve both as an intracellular signalling compartment and as
      an organizing platform orchestrating many vital processes in eukaryotic cells. It
      has become clear that the LDs-confined deposition and lipolytic degradation of
      neutral lipids define longevity in multicellular eukaryotic organisms and yeast.
      We summarize the evidence in support of the essential role that LDs play in
      longevity regulation and propose several molecular mechanisms by which these
      dynamic organellar compartments control the aging process in multicellular
      eukaryotes and yeast.

PMID- 19754451
TI  - Lipid order and molecular assemblies in the plasma membrane of eukaryotic cells.
AB  - Multimolecular assemblies on the plasma membrane exhibit dynamic nature and are
      often generated during the activation of eukaryotic cells. The role of lipids and
      their physical properties in helping to control the existence of these structures
      is discussed. Technological improvements for live cell imaging of membrane
      components are also reviewed.

PMID- 19754452
TI  - GRAF1-dependent endocytosis.
AB  - The role of endocytosis in controlling a multitude of cell biological events is
      well established. Molecular and mechanistic characterization of endocytosis has
      predominantly focused on CME (clathrin-mediated endocytosis), although many other
      endocytic pathways have been described. It was recently shown that the BAR
      (Bin/amphiphysin/Rvs) and Rho GAP (GTPase-activating protein) domain-containing
      protein GRAF1 (GTPase regulator associated with focal adhesion kinase-1) is found
      on prevalent, pleiomorphic endocytic membranes, and is essential for the major,
      clathrin-independent endocytic pathway that these membranes mediate. This pathway
      is characterized by its ability to internalize GPI (glycosylphosphatidylinositol)
      anchored proteins, bacterial toxins and large amounts of extracellular fluid.
      These membrane carriers are highly dynamic and associated with the activity of
      the small G-protein Cdc42 (cell division cycle 42). In the present paper, we
      review the role of GRAF1 in this CLIC (clathrin-independent carrier)/GEEC (GPI
      anchored protein-enriched early endocytic compartment) endocytic pathway and
      discuss the current understanding regarding how this multidomain protein
      functions at the interface between membrane sculpting, small G-protein signalling
      and endocytosis.

PMID- 19754453
TI  - Bicaudal-D and its role in cargo sorting by microtubule-based motors.
AB  - Many cytoplasmic cargoes are transported along microtubules using dynein or
      kinesin molecular motors. As the sorting machinery of the cell needs to be
      tightly controlled, associated factors are employed to either recruit cargoes to
      motors or to regulate their activities. In the present review, we concentrate on
      the BicD (Bicaudal-D) protein, which has recently emerged as an essential element
      for transport of several important cargoes by the minus-end-directed motor
      cytoplasmic dynein. BicD was proposed to be a linker bridging cargo and dynein,
      although recent studies suggest that it may also have roles in the regulation of
      cargo motility. Here we summarize the current knowledge of the role that BicD
      plays in the transport of diverse cellular constituents. We catalogue the
      molecular interactions that underpin these functions and also highlight important
      questions to be addressed in the future.

PMID- 19754454
TI  - The role of vesicle trafficking in epithelial cell motility.
AB  - Cell motility is important for many physiological and pathological processes
      including organ development, wound healing, cancer metastasis and correct immune
      responses. In particular, epithelial wound healing is both a medically relevant
      topic and a common experimental model. Mechanisms underlying generation of a
      polarized cell and maintenance of a motile phenotype during steady-state
      migration are not well understood. Polarized trafficking of bulk membrane and
      cell adhesion molecules has been implicated in regulation of cell motility. The
      present review focuses on the role of different trafficking pathways in
      epithelial cell migration, including clathrin-mediated endocytosis, caveolar
      endocytosis, exocytosis of biosynthetic cargo, 'short-loop' and 'long-loop'
      endosomal recycling.

PMID- 19754455
TI  - Employing multiple models, methods and mechanisms in bipolar disorder research.
AB  - BD (bipolar disorder) is a devastating condition, giving rise to debilitating
      mood swings and a greatly increased likelihood of suicide. Research into the
      origins, progression and treatment of BD has been slow, primarily due to lack of
      suitable model systems for BD research. However, the complexity of the
      neurological basis for mood, variability in patient populations and the lack of
      clear readouts for BD diagnosis also provide significant problems for research in
      this area. In this Biochemical Society Focused Meeting, held at Royal Holloway
      University of London, approx. 40 national and international delegates met to
      discuss current research into understanding BD. The talks presented at this
      conference covered research examining the genetic basis of the disorder, changes
      in patient populations, pharmacological actions of BD drugs and the development
      of new models systems for this research. The focus of these talks and the
      following papers is to help to unify and disseminate research into this important
      but poorly understood medical condition.

PMID- 19754456
TI  - Neural network dysfunction in bipolar depression: clues from the efficacy of
      lamotrigine.
AB  - One strategy to understand bipolar disorder is to study the mechanism of action
      of mood-stabilizing drugs, such as valproic acid and lithium. This approach has
      implicated a number of intracellular signalling elements, such as GSK3beta
      (glycogen synthase kinase 3beta), ERK (extracellular-signal-regulated
      kinase)/MAPK (mitogen-activated protein kinase) or protein kinase C. However,
      lamotrigine does not seem to modulate any of these targets, which is intriguing
      given that its profile in the clinic differs from that of valproic acid or
      lithium, with greater efficacy to prevent episodes of depression than mania. The
      primary target of lamotrigine is the voltage-gated sodium channel, but it is
      unclear why inhibition of these channels might confer antidepressant efficacy. In
      healthy volunteers, we found that lamotrigine had a facilitatory effect on the
      BOLD (blood-oxygen-level-dependent) response to TMS (transcranial magnetic
      stimulation) of the prefrontal cortex. This effect was in contrast with an
      inhibitory effect of lamotrigine when TMS was applied over the motor cortex. In a
      follow-up study, a similar prefrontal specific facilitatory effect was observed
      in a larger cohort of healthy subjects, whereas valproic acid inhibited motor and
      prefrontal cortical TMS-induced BOLD response. In vitro, we found that
      lamotrigine (3-10 microM) enhanced the power of gamma frequency network
      oscillations induced by kainic acid in the rat hippocampus, an effect that was
      not observed with valproic acid (100 microM). These data suggest that lamotrigine
      has a positive effect on corticolimbic network function that may differentiate it
      from other mood stabilizers. The results are also consistent with the notion of
      corticolimbic network dysfunction in bipolar disorder.

PMID- 19754457
TI  - Risk and resilience in bipolar disorder: rationale and design of the
      Vulnerability to Bipolar Disorders Study (VIBES).
AB  - BD (bipolar disorder) is among the ten most significant causes of disability
      worldwide. Neuroscientists and clinicians have yet to meet the challenge of
      reducing this disability burden. The main obstacle to date has been our
      incomplete understanding of the pathophysiology of BD which thwarts primary
      prevention and early diagnosis and hinders effective treatment. There is a need
      to move beyond diagnostic approaches based purely on behavioural observation, as
      they lack reliability and biological validity. The present article reviews the
      evidence for cognitive, brain structural and functional correlates of genetic
      predisposition to BD and highlights biological markers of risk as well as factors
      that might protect against disease expression. It also outlines the rational and
      design of the Vulnerability to Bipolar Disorders Study (VIBES), which exemplifies
      a promising approach to delineating biological mechanisms mediating risk,
      resilience and disease expression in BD.

PMID- 19754458
TI  - The role of lithium in modulation of brain genes: relevance for aetiology and
      treatment of bipolar disorder.
AB  - Bipolar disorder is a debilitating disorder of the brain with a lifetime
      prevalence of 1.0% for bipolar I, 1.1% for bipolar II disorder and 2.4-4.7% for
      subthreshold bipolar disorder. Medications, including lithium, have demonstrated
      efficacy in the treatment of bipolar disorder, but their molecular targets and
      mode of action are largely unknown. A few studies have begun to shed light on
      potential targets of lithium treatment that may be involved in lithium's
      therapeutic effect. We have recently conducted a microarray study of rat frontal
      cortex following chronic treatment (21 days) with lithium. Chronic treatment with
      lithium led to a significant (at least 1.5-fold) down-regulation of 151 genes and
      up-regulation of 57 genes. We discuss our results in the context of previous
      microarray studies involving lithium and gene-association studies to identify key
      genes associated with chronic lithium treatment. A number of genes associated
      with bipolar disorder, including Comt (catechol-O-methyltransferase), Vapa
      (vesicle-associated membrane protein-associated protein A), Dtnb (dystrobrevin
      beta) and Pkd1 (polycystic kidney disease 1), were significantly altered in our
      microarray dataset along with genes associated with synaptic transmission,
      apoptosis and transport among other functions.

PMID- 19754459
TI  - DTI studies of corpus callosum in bipolar disorder.
AB  - Although the pathogenesis of bipolar disorder is still not completely understood,
      there is evidence from imaging studies that abnormalities in inter-hemispheric
      communication may play a major role in the pathophysiology of bipolar disorder.
      In the present review, we discuss the most consistent findings from diffusion
      imaging studies exploring corpus callosum integrity in bipolar disorder.

PMID- 19754460
TI  - Cellular consequences of inositol depletion.
AB  - The inositol-depletion hypothesis was suggested to explain the therapeutic
      mechanism of mood-stabilizing drugs. Focus was previously on the
      phosphatidylinositol signalling pathway and on the regulatory roles of
      Ins(3,4,5)P(3) and DAG (diacylglycerol). Recent findings indicate that inositol
      and inositol-containing molecules, including phosphoinositides and inositol
      phosphates, have signalling and regulatory roles in many cellular processes. This
      suggests that depleting inositol may lead to perturbation of a wide range of
      cellular functions, at least some of which may be associated with bipolar
      disorder.

PMID- 19754461
TI  - Is the brain arachidonic acid cascade a common target of drugs used to manage
      bipolar disorder?
AB  - Although lithium has been used therapeutically to treat patients with bipolar
      disorder for over 50 years, its mechanism of action, as well as that of other
      drugs used to treat bipolar disorder, is not agreed upon. In the present paper, I
      review studies in unanaesthetized rats using a neuropharmacological approach,
      combined with kinetic, biochemical and molecular biology techniques,
      demonstrating that chronic administration of three commonly used mood stabilizers
      (lithium, valproic acid and carbamazepine), at therapeutically relevant doses,
      selectively target the brain arachidonic acid cascade. Upon chronic
      administration, lithium and carbamazepine decrease the binding activity of
      activator protein-2 and, in turn, the transcription, translation and activity of
      its arachidonic acid-selective calcium-dependent phospholipase A(2) gene product,
      whereas chronic valproic acid non-competitively inhibits long-chain acyl-CoA
      synthetase. The net overlapping effects of the three mood stabilizers are
      decreased turnover of arachidonic acid, but not of docosahexaenoic acid, in rat
      brain phospholipids, as well as decreased brain cyclo-oxygenase-2 and
      prostaglandin E(2). As an extension of this theory, drugs that are thought to
      induce switching to mania, especially when administered during bipolar depression
      (fluoxetine and imipramine), up-regulate enzymes of the arachidonic acid cascade
      and turnover of arachidonic acid in rat brain phospholipids. Future basic and
      clinical studies on the arachidonic acid hypothesis of bipolar disorder are
      warranted.

PMID- 19754462
TI  - PtdIns(3,4,5)P(3) and inositol depletion as a cellular target of mood
      stabilizers.
AB  - Lithium (Li(+)) is the mood stabilizer most frequently used in the treatment of
      bipolar mood disorder; however, its therapeutic mechanism is unknown. In the
      1980s, Berridge and colleagues proposed that Li(+) treatment acts via inhibition
      of IMPase (inositol monophosphatase) to deplete the cellular concentration of myo
      inositol. Inositol depletion is also seen with the alternative mood stabilizers
      VPA (valproic acid) and CBZ (carbamazepine), suggesting a common therapeutic
      action. All three drugs cause changes in neuronal cell morphology and cell
      chemotaxis; however, it is unclear how reduced cellular inositol modulates these
      changes in cell behaviour. It is often assumed that reduced inositol suppresses
      Ins(1,4,5)P(3), a major intracellular signal molecule, but there are other
      important phosphoinostide-based signal molecules in the cell. In the present
      paper, we discuss evidence that Li(+) has a substantial effect on
      PtdIns(3,4,5)P(3), an important signal molecule within the nervous system. As
      seen for Ins(1,4,5)P(3) signalling, suppression of PtdIns(3,4,5)P(3) signalling
      also occurs via an inositol-depletion mechanism. This has implications for the
      cellular mechanisms controlling phosphoinositide signalling, and offers insight
      into the genetics underlying risk of bipolar mood disorder.

PMID- 19754463
TI  - Valproic acid- and lithium-sensitivity in prs mutants of Saccharomyces
      cerevisiae.
AB  - Prs [PRPP (phosphoribosyl pyrophosphate) synthetase] catalyses the transfer of
      pyrophosphate from ATP to ribose 5-phosphate, thereby activating the pentose
      sugar for incorporation into purine and pyrimidine nucleotides. The Saccharomyces
      cerevisiae genome contains five genes, PRS1-PRS5, whose products display
      characteristic PRPP and bivalent-cation-binding sites of Prs polypeptides.
      Deletion of one or more of the five PRS genes has far-reaching and unexpected
      consequences, e.g. impaired cell integrity, temperature-sensitivity and
      sensitivity to VPA (valproic acid) and LiCl. CTP pools in prs1Delta and prs3Delta
      are reduced to 12 and 31% of the wild-type respectively, resulting in an
      imbalance in phospholipid metabolism which may have an impact on the
      intracellular inositol pool which is affected by the administration of either VPA
      or LiCl. Overexpression of CTP synthetase in prs1Delta prs3Delta strains
      partially reverses the VPA-sensitive phenotype. Yeast two-hybrid screening
      revealed that Prs3 and the yeast orthologue of GSK3 (glycogen synthase kinase 3),
      Rim11, a serine/threonine kinase involved in several signalling pathways,
      interact with each other. Furthermore, Prs5, an essential partner of Prs3, which
      also interacts with GSK3 contains three neighbouring phosphorylation sites,
      typical of GSK3 activation. These studies on yeast PRPP synthetases bring
      together and expand the current theories for the mood-stabilizing effects of VPA
      and LiCl in bipolar disorder.

PMID- 19754464
TI  - Knockout mice in understanding the mechanism of action of lithium.
AB  - Lithium inhibits IMPase (inositol monophosphatase) activity, as well as inositol
      transporter function. To determine whether one or more of these mechanisms might
      underlie lithium's behavioural effects, we studied Impa1 (encoding IMPase) and
      Smit1 (sodium-myo-inositol transporter 1)-knockout mice. In brains of adult
      homozygous Impa1-knockout mice, IMPase activity was found to be decreased;
      however, inositol levels were not found to be altered. Behavioural analysis
      indicated decreased immobility in the forced-swim test as well as a strongly
      increased sensitivity to pilocarpine-induced seizures. These are behaviours
      robustly induced by lithium. In homozygous Smit1-knockout mice, free inositol
      levels were decreased in the frontal cortex and hippocampus. These animals behave
      like lithium-treated animals in the model of pilocarpine seizures and in the
      Porsolt forced-swim test model of depression. In contrast with O'Brien et al.
      [O'Brien, Harper, Jove, Woodgett, Maretto, Piccolo and Klein (2004) J. Neurosci.
      24, 6791-6798], we could not confirm that heterozygous Gsk3b (glycogen synthase
      kinase 3beta)-knockout mice exhibit decreased immobility in the Porsolt forced
      swim test or decreased amphetamine-induced hyperactivity in a manner mimicking
      lithium's behavioural effects. These data support the role of inositol-related
      processes rather than GSK3beta in the mechanism of the therapeutic action of
      lithium.

PMID- 19754465
TI  - Structure-function studies for the panacea, valproic acid.
AB  - The anticonvulsant properties of VPA (valproic acid), a branched short-chain
      fatty acid, were serendipitously discovered in 1963. Since then, therapeutic
      roles of VPA have increased to include bipolar disorder and migraine prophylaxis,
      and have more recently been proposed in cancer, Alzheimer's disease and HIV
      treatment. These numerous therapeutic roles elevate VPA to near 'panacea' level.
      Surprisingly, the mechanisms of action of VPA in the treatment of many of these
      disorders remain unclear, although it has been shown to alter a wide variety of
      signalling pathways and a small number of direct targets. To analyse the
      mechanism of action of VPA, a number of studies have defined the structural
      characteristics of VPA-related compounds giving rise to distinct therapeutic and
      cellular effects, including adverse effects such as teratogenicity and
      hepatotoxicity. These studies raise the possibility of identifying target
      specific novel compounds, providing better therapeutic action or reduced side
      effects. This short review will describe potential therapeutic pathways targeted
      by VPA, and highlight studies showing structural constraints necessary for these
      effects.

PMID- 19754466
TI  - Validating GSK3 as an in vivo target of lithium action.
AB  - Lithium is widely used to treat bipolar disorder, but its mechanism of action in
      this disorder is unknown. Lithium directly inhibits GSK3 (glycogen synthase
      kinase 3), a critical regulator of multiple signal transduction pathways.
      Inhibition of GSK3 provides a compelling explanation for many of the known
      effects of lithium, including effects on early development and insulin
      signalling/glycogen synthesis. However, lithium also inhibits inositol
      monophosphatase, several structurally related phosphomonoesterases,
      phosphoglucomutase and the scaffolding function of beta-arrestin-2. It is not
      known which of these targets is responsible for the behavioural or therapeutic
      effects of lithium in vivo. The present review discusses basic criteria that can
      be applied to model systems to validate a proposed direct target of lithium. In
      this context, we describe a set of simple behaviours in mice that are robustly
      affected by chronic lithium treatment and are similarly affected by structurally
      diverse GSK3 inhibitors and by removing one copy of the Gsk3b gene. These
      observations, from several independent laboratories, support a central role for
      GSK3 in mediating behavioural responses to lithium.

PMID- 19754467
TI  - Investigation of the H(+)-myo-inositol transporter (HMIT) as a neuronal regulator
      of phosphoinositide signalling.
AB  - Phosphoinositide signalling regulates a series of important neuronal processes
      that are thought to be altered in mood disorders. Furthermore, mood-stabilizing
      drugs inhibit key enzymes that regulate phosphoinositide production and alter
      neuronal growth cone morphology in an inositol-reversible manner. Inositol is
      taken up by neurons from the extracellular fluid, presumably via membrane
      transporters; it can also be synthesized by the enzyme MIP-synthase (myo-inositol
      1-phosphate synthase) and, in addition, it is generated by inositol phospholipid
      hydrolysis. The neuronal-specific HMIT (H(+)-myo-inositol transporter) represents
      a potential regulator of inositol signalling in neurons that warrants further
      investigation.

PMID- 19754468
TI  - Bosnian journal of basic medical sciences. Editorial.

PMID- 19754469
TI  - Comparative analysis of gene transfer to human and rat retinal pigment epithelium
      cell line by a combinatorial use of recombinant adeno- associated virus and
      ultrasound or/and microbubbles.
AB  - Ultrasound-targeted microbubble destruction has been utilized to deliver a
      drug/gene into cells in both in vitro and in vivo studies. This work was
      performed to investigate the feasibility of gene transfer to human retinal
      pigment epithelium cell line(ARPE-19) and rat retinal pigment epithelium cell
      line(RPE-J) by a combinatorial use of recombinant adeno-associated virus (rAAV)
      and ultrasound (US) or/and microbubbles (MBs) and compare the difference between
      them. Different doses of serotype 2 rAAV encoding a enhanced green fluorescent
      protein (rAAV2-EGFP) gene and MBs was administered to ARPE-19 and RPE-J cells
      under different US conditions. Transfection efficiency and cell viability were
      assessed by fluorescence microscopy, flow cytometry (FCM) analysis, trypan blue
      staining. The results indicated that US and MBs could respectively improve rAAV2
      mediated gene transfer to RPE-J cells, but neither US nor MBs could do so in ARPE
      19 cells. US plus MBs could significantly enhance rAAV2-mediated gene transfer to
      ARPE-19 cells, however, the same effects were not seen in RPE-J cells. These
      findings demonstrated it is not always coincident that US, MBs and US plus MBs
      exert the similar effects on gene transfer in vitro RPE cells. So, it is
      necessary to choose appropriate RPE cell line for the study of US or/and MBs
      mediated rAAV gene transfer in retinal gene therapy.

PMID- 19754470
TI  - Evaluation of cardiovascular risk in school children.
AB  - Atherosclerosis is a pathological condition that begins in early childhood, but
      clinically the disease manifests in older age. The aim of work was to determine
      frequency of atherosclerosis risk factors in healthy school children. Cross
      sectional study included 214 children in mean age 10,99+/-2,52 years, within
      range 7 to 15 years. Patients body mass index, blood pressure, lipid status,
      dietary habits, physical activity and sedentary habits have been evaluated.
      Cardiovascular risk factors are significantly present in children (P<0,05) i.e.
      one cardiovascular risk factor is present in 47/214 (21,96%) children, two risk
      factors had 25/214 (11,68%) children, while 17/214 (7,94%) children had three or
      more cardiovascular risk factors. Obesity was present in 20/214 (9,34%) children,
      while overweight was present in 23/214 (10,74%) children. Hypertension was
      present in 10/214 (4,67%) children, and it was significantly present (p<0,05) in
      obese and overweight children. Total cholesterol was increased in 17/214 (7,94%)
      children, LDL-cholesterol was increased in 11/214 (5,14%) [corrected], increased
      triglycerides had 4/214 (1,86%) children, while decreased HDL-cholesterol was
      found in (3/214, 1,40%) children. Unhealthy dietary habits were present in 45/214
      (21,02%) children, 42/214 (19,62%) children is physically inactive, while
      sedentary habits were shown in 39/214 (18,22%) children. Research shows that a
      large number within study group has one or more cardiovascular risk factors that
      can lead to premature atherosclerosis. Using massive screening of cardiovascular
      risk factors, along with adequate physical activity, healthy dietary habits,
      reduced sedentary habits, doctors and teacher's education, parents and children
      can reduce premature clinical sequels in atherosclerotic process.

PMID- 19754471
TI  - Correlation between bulbar axis length and retinal ruptures in case of myopia
      eye.
AB  - In this study, we analysed 180 eyes with myopia in order to determine the
      "critical" length of bulbar axis for the occurrence of retinal ruptures as the
      main cause for retinal detachment. After the focused ophthalmological assessment,
      ultrasonic measurement of the bulbar axis length, indirect binocular
      ophtalmoscopy, we analysed diagnosed retinal ruptures according to the shape and
      axis length. Mean age of our patients was between 48,43 and to 51,60 years with
      SD ranging from 13,88 to 18,45. The study included 102 (56,6%) male and 78
      (43,3%) female patients; there was no statistically significant difference
      regarding the occurrence of retinal ruptures between male and female patients
      compared to the axis length. Most dominant was round (28,2%), then oval (25%)
      category - multiple small ruptures (19,2%), and horseshoe-shaped (15,3%), and
      finally the ruptures with operculum. We consider the length of bulbar axis
      ranging from 24,52 mm to 26,51 mm to be a predictive factor in the occurrence of
      retinal rupture, and later in retinal detachment.

PMID- 19754472
TI  - Expression and clinical significance of p120 catenin mRNA and protein in
      pancreatic carcinoma.
AB  - The aim of this work was investigate the association of P120 catenin expression
      with the clinicopathologic features and prognosis of pancreatic carcinoma. RT-PCR
      was performed to investigate the expression of P120 catenin mRNA and western
      blotting were performed to investigate the expression of P120 catenin protein in
      52 patients with pancreatic carcinoma. The relationships between P120 catenin
      expression and clinicopathological characteristics and prognosis were analyzed.
      The mRNA and protein expression of P120 catenin detected by RT-PCR and western
      blotting in pancreatic carcinoma was significantly lower than that in normal
      pancreatic tissues (0.227+/-0.067 vs 0.793+/-0.162, t=9.157, P =0.000; 0.665+/
      0.192 vs 0.936+/-0.251, t=3.857, P=0.002). Reduced expression of P120 catenin
      mRNA and protein was significantly correlated with lymph node metastasis (P
      =0.004, P =0.006), vascular invasion (P =0.022, P =0.039 ), distant metastasis (P
      =0.037 , P =0.025), differentiated (P =0.033, P =0.013) and pTNM stage (P =0.003,
      P =0.022) of tumours. Additionally, reduced expression of P120 catenin mRNA and
      protein in tumour correlated with a worse prognosis and normal expression with a
      better survival rate (P=0.022, P=0.007). The reduced expression of both P120
      catenin mRNA and protein in pancreatic carcinoma suggest that low expressions
      relate to pancreatic carcinoma development. P120 catenin may be related to
      pancreatic carcinoma behaviour and be a potential prognostic molecule.

PMID- 19754473
TI  - Evaluation and importance of selected microbiological methods in the diagnosis of
      human brucellosis.
AB  - Brucellosis is an important public health problem in Bosnia and Herzegovina. The
      diagnosis of brucellosis in the country without any experiences with this kind of
      infection may be very difficult. The aim of this study was to evaluate diagnostic
      methods: Rose Bengal test, blood cultures and ELISA IgM and IgG in the patients
      with brucellosis. The study included 91 brucellosis patients in the period 2004
      to 2007. All the patients were treated at the Clinic for Infectious Diseases,
      University of Sarajevo Clinics Centre. Blood cultures were positive in 28/91 (30,
      8%) patients. This method often needs a long period of incubation and specimens
      need to be obtained early. These limitations make serology the most useful tool
      for the laboratory diagnosis of Brucella infection. Rose Bengal is a rapid plate
      agglutination test, very sensitive irrespective of the stage of the disease. In
      our study, Rose Bengal test was positive in all patients 91/91 (100, 0%).
      Brucella IgM antibodies with ELISA were positive in 59/91 (64, 8%). Brucella IgG
      antibodies with ELISA were positive in 51/91 (56%). In order to determine the
      diagnostic value of the different tests, we compared the sensitivity among test
      methods: Rose Bengal test-100.0%, blood culture-30.8%, ELISA IgM-64.8% and ELISA
      IgG-56.1%. Sensitivity of test methods was different in the different stages of
      illness. It is necessary to use combination of different tests such are blood
      culture, Rose Bengal test and ELISA in order to ensure the diagnosis. Rose Bengal
      test is excellent for the screening. Blood culture is a method of choice for the
      diagnosis acute infection. ELISA is a very good method for the diagnostic chronic
      disease and relapse.

PMID- 19754474
TI  - The role of nitric oxide and ferritin in the pathogenesis of alcoholic liver
      disease: a controlled clinical study.
AB  - The role of ferritin in fibrogenesis of liver parenchyma in patients with
      alcoholic liver disease has been investigated in previous studies. Ferritin was
      shown to be an indirect marker of ferum deposition in liver parenchyma in alcohol
      liver disease. The aim of the present study was to examine the role of nitric
      oxide (NO) in the pathogenesis of alcoholic liver disease as well as the
      influence of NO on iron (ferritin) metabolism in patients with alcoholic liver
      disease. Serum concentrations of NO and iron markers (iron, total iron binding
      capacity, ferritin) were measured in 30 male patients (aged 20-60 years) with
      alcoholic liver disease, as well as from a control group (30 male patients (aged
      20-60 years) without liver disease). NO concentration was detected by measuring
      production of nitrates and nitrites using classical colorimetric Griess
      reactions. There was a statistically significant increase in serum NO
      concentration in patients with alcoholic liver disease compared to the control
      group (mean +/- SEM; 41,2 +/- 25,3 vs. 28,9 +/- 12,3 mmol/dm3, respectively;
      p<0,03). Similarly, serum iron levels (18,7 +/- 8,2 vs. 13,2 +/- 10,2 g/100 cm3,
      respectively; p<0,03) and serum total iron binding capacity (51,3 +/- 13,9 vs.
      41,4 +/- 11,4 micromol/dm3, respectively; p<0,005) were also significantly higher
      in patients with alcoholic liver disease compared to control patients. The serum
      concentration of ferritin was 27% higher in patients with alcoholic liver disease
      than in the control group; however this was not statistically significant (283,2
      +/- 291,0 vs. 222,9 +/- 252,0 g, respectively; p<0,4). There was no correlation
      between NO and ferritin in the investigated groups. These results suggest a
      possible role of NO and iron in the pathogenesis of alcoholic liver disease. NO
      and iron may be used as non-invasive predictors of liver damage. Also the role of
      iron in sera, and its deposition in liver parenchyma, could be used in clinical
      practice, especially in regards to assessing the fibrogenesis of liver parenchyma
      induced by ferritin.

PMID- 19754475
TI  - Implant supported prosthesis in a patient with progeria: case report.
AB  - Prosthodontic rehabilitation can be accomplished with fixed, overdenture,
      complete, or implant-retained prostheses. Dental treatment overcomes the
      patient's functional, psychological, esthetic and phonation problems. Remaining
      healthy teeth may allow the dentist to fabricate a removable partial overdenture,
      fixed partial prosthesis or implant - supported prosthesis. The retention of a
      number of abutments helps maintain a positive ridge form with greater height and
      volume of the alveolar bone, improving masticatory performance, as well as
      providing a more stable prostheses. Dental patients who have medical problems
      need many treatment procedures. Multidisciplinary treatment planning is
      invaluable for patient's dental health. Progeria is a rare genetic condition
      where symptoms resembling aspects of aging are manifested at an early age.
      characteristic clinical findings of Progeria disease include abnormalities of the
      skin and hair in conjunction with characteristic facial features and skeletal
      abnormalities. The characteristic facies show protruding ears, beaked nose, thin
      lips with centrofacial cyanosis, prominent eyes, frontal and parietal bossing
      with pseudohydrocephaly, midface hypoplasia with micrognathia and large anterior
      fontanel. The other reported anomalies are dystrophic nails, hypertrophic scars
      and hypoplastic nipples. The findings that are nearly interested in dentistry are
      delayed dentition, anodontia, hypodontia, or crowding of teeth. This article
      presents the multidisciplinary dental treatment planning includes surgical,
      endodontic and prosthetic treatment of a patient with a history of progeria. In
      this case complete-arch fixed prostheses in both maxilla and mandible, supported
      by a combination of implants and teeth are reported.

PMID- 19754476
TI  - Decreased serum lipids in patients with probable Alzheimer's disease.
AB  - Alzheimer;s disease (AD) is a multifactorial disease but its aetiology and
      pathophisiology are still not fully understood. Epidemiologic studies examining
      the association between lipids and dementia have reported conflicting results.
      High total cholesterol has been associated with both an increased, and decreased,
      risk of AD and/or vascular dementia (VAD), whereas other studies found no
      association. The aim of this study was to investigate the serum lipids
      concentration in patients with probable AD, as well as possible correlation
      between serum lipids concentrations and cognitive impairment. Our cross-sectional
      study included 30 patients with probable AD and 30 age and sex matched control
      subjects. The probable AD was clinically diagnosed by NINCDS-ADRDA criteria.
      Serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and
      triglyceride (TG) levels were determined at the initial assessment using standard
      enzymatic colorimetric techniques. Low-density lipoprotein cholesterol (LDL-C)
      and very low density lipoprotein cholesterol (VLDL-C) levels were calculated.
      Subjects with probable AD had significantly lower serum TG (p<0,01), TC (p<0,05),
      LDL-C (p<0,05) and VLDL-C (p<0,01) compared to the control group. We did not
      observe significant difference in HDL-C level between patients with probable AD
      and control subjects. Negative, although not significant correlation between TG,
      TC and VLDL-C and MMSE in patients with AD was observed. In the control group of
      subjects there was a negative correlation between TC and MMSE but it was not
      statistically significant (r = -0,28). Further studies are required to explore
      the possibility for serum lipids to serve as diagnostic and therapeutic markers
      of AD.

PMID- 19754477
TI  - Anemia identified one month after renal transplantation is predictive of anemia
      identified after twelve months.
AB  - The aim of this study was to evaluate whether anemia identified earlier than 3
      months postengraftment in modern era could be predictive of anemia at 12 months.
      Cross-sectional and cohort studies based on retrospective analysis of existing
      clinical records were performed. Data on recipient's age at transplantation,
      follow-up serum creatinine (SCR) and hemoglobin (Hb) on day 7 (D7), at month 1
      (M1) and at month 3 (M3) postengraftment were collected. Outcome was anemia
      identified at 12 months (M12) postengraftment. There were 75 patients on D7, 74
      at M1 and 61 at M3. Multiple linear regression model that included recipient's
      age at transplantation, Hb and creatinine on D7 and tested the risk for anemia at
      M12 retained only the age in the model, with the coefficient of 0,84 (P=0,001).
      The same model at M1 retained Hb and age, with the coefficients of 0,26 (P=0,03)
      and 0,81 (P=0,0002), respectively and at M3 it retained Hb and age, with the
      coefficients of 0,41 (P=0,004) and 0,70 (P=0,003), respectively. Anemia
      identified at M1 after renal transplantation is predictive of anemia at M12.

PMID- 19754478
TI  - The effects of antenatal corticosteroids and surfactant replacement on neonatal
      respiratory distress syndrome.
AB  - The goal of this study was to determine the effects of antenatal corticosteroids
      and surfactant replacement on the severity and frequency of Respiratory Distress
      Syndrome (RDS) in a cohort of premature infants born in Sarajevo, Bosnia and
      Herzegovina, from 2005 to 2007. The cohort consisted of 172 premature neonates
      with estimated gestational age between 26 and 34 weeks. Babies with IUGR, babies
      of diabetic mothers and babies with major congenital defects were excluded. Out
      of 172 neonates, 80 were treated antenatally with corticosteroids (single course
      of dexamethasone) and 92/172 were not. There was no statistical difference
      (p>0,5) in average gestational age (31,2 vs. 31,0 GW) and male/female ratio
      between investigated groups; there were significantly more male patients (p<0,05)
      in both groups. Frequency of RDS was significantly lower in the corticosteroid
      group (24/80) in relation to the control group (54/92) (p<0,001). Severe RDS was
      significantly (p<0,01) more frequent in the control group 34/53 (62,96%) then in
      the corticosteroid group 6/24 (25,0%). Bovine surfactant (Survanta) was given as
      a rescue therapy to 78 babies with clinical and radiological signs of RDS who
      required FiO2>0,40 and mechanical ventilation. Early surfactant administration
      within six hours after birth appeared to be effective at reducing mortality then
      later surfactant administration (p<0,005). In the group of babies requiring FiO2>
      or =0,6 at the time of surfactant replacement, the mortality rate was
      significantly higher (p<0,05). In conclusion, we confirm the efficacy of
      antenatal corticosteroid treatment and early surfactant treatment in a cohort of
      premature infants born in Sarajevo.

PMID- 19754479
TI  - Clinical dilemmas and surgical treatment of penoscrotal, scrotal and perineal
      hypospadias.
AB  - Hypospadia is the most common congenital malformation of the urinary tract. It is
      a malformation with the opening of the urethra proximally from the usual site.
      The meatal opening can be anywhere alone the shaft of the penis, or in more
      severe forms, within the scrotum, or in the perineum. Consequently the
      hypospadias can be distal, medial and proximal. The proximal ones can be
      penoscrotal (PS), scrotal (SC) and perineal (PE). The cause of hypospadias is
      largely unknown; however, current epidemiology and laboratory studies have shed
      new light into the etiology of hypospadias. With recent advancements in molecular
      biology, microarray technology, it appears that hypospadias is potentially
      related to disrupted gene expression. Currently, the only available treatment is
      surgery. The aim of this study was to present our results of the surgical
      correction of hypospadias and methods used to answer the clinical dilemmas about
      the gender. Authors have used two methods for a surgical resolution of the
      hypospadia - one-step operation suggested by Snodgrass and two-step operation,
      employing free graft suggested by Bracka. Clinical dilemmas regarding the gender
      were answered using cytogenetic assessment through lymphocyte cultivation method,
      suggested by Seabright. The cytogenetic assessment was carried in 23 patients
      with proximal hypospadia (penoscrotal, scrotal and perineal). Characteristic male
      cariotype (46, XY) was found in 22 patients. In one patient, with scrotal
      hypospadia, we found the characteristic female cariotype. This patient had
      testicles. The patient with female cariotype had a TDG gene that determines the
      differentiation of the testicles. Although surgery remains the only therapy for
      the treatment of the hypospadias, better understanding of the molecular and
      hormonal mechanisms behind the diseases may contribute to the prevention and the
      decrease in the incidence of the malformation. Cytogenetic testing in patients
      with unclear gender is important in planning further treatment.

PMID- 19754480
TI  - Insulin resistance and C-reactive protein in preeclampsia.
AB  - Preeclampsia is referred to as the "disease of the theories" because of the
      multiple hypotheses proposed to explain is occurrence. Despite considerable
      research, the causes of preeclampsia remain unclear. Preeclampsia is likely to be
      multifactorial in origin, and recent research has focused on endothelial
      dysfunction as a central abnormality in preeclampsia. Insulin resistance and
      inflammation may contribute to the onset of preeclampsia. They could also be
      correlated. The aim of the study was to evaluate the presence and relationship
      between insulin resistance and its markers and C-reactive protein as a marker of
      inflammation. During their third trimester, 17 preeclamptic women and 20
      normotensive controls underwent oral glucose tolerance test, basic biochemical
      analyses and SHBG. Preeclamptic women were more insulin resistant (p=0,004), and
      they had higher triglycerides levels (p=0,006), uric acid (p=0,002). However, the
      study groups did not differ in C-reactive protein (CRP), sex hormone-binding
      globulin (SHBG), high and low-density lipoproteins (HDL-cholesterol and LDL
      cholesterol). In multiple regression analysis only SHBG (p=0,014) and
      triglycerides (p=0,003) were associated with insulin sensitivity independently of
      the body mass index (BMI), weight gain, HDL and LDL, and CRP. Preeclampsia is a
      state of increased insulin resistance, and CRP as the marker of inflammation was
      not increased in our research, and not associated with established preeclampsia.

PMID- 19754481
TI  - Pentoxifylline ameliorates glomerular basement membrane ultrastructural changes
      caused by gentamicin administration in rats.
AB  - Gentamicin is commonly used for the treatment of severe gram negative bacterial
      infections but inevitably cause renal failure during prolonged use. The aim of
      our study was to emphasize protective effects of pentoxifylline on glomerular
      basement membrane (GBM) alterations induced by gentamicin in rats. Experiments
      were done on 40 male Wistar rats divided in three experimental groups. GM-group
      was treated daily with gentamicin in dose of 100 mg/kg during 8 days. PTX-group
      was treated daily with pentoxifylline in dose of 45 mg/kg and the same dose of
      gentamicin as in GM-group during 8 days. The control group received 1 ml/day
      saline intraperitoneally. Morphometric parameter measured during the analysis was
      glomerular basement membrane thickness. In GM-group of animals glomeruli were
      enlarged and GMB was diffusely and unequally thickened with neutrophil cells
      infiltration. In proximal tubules epithelial cells, vacuolization of cytoplasm
      with coagulation-type necrosis were observed. In PTX-group of animals glomeruli
      were somewhat enlarged and GBM was thickened only in some segments. Coagulation
      type necrosis was not found. Blood urea and serum creatinine concentration in GM
      group were significantly elevated in comparison with PTX-group while potassium
      level was decreased. Our results suggest that PTX has protective effects on GBM
      and proximal tubules in GM-treated rats.

PMID- 19754482
TI  - Influence of splitting on dissolution properties of metoprolol tablets.
AB  - The objective of this work was to compare several profiles of dissolution data
      for metoprolol controlled release tablet formulations in order to identify
      possible changes in dissolution profiles of whole and scored tablets. Adequate
      design of score lines (on one or both sides) as well as the technology of
      preparation of tablet mixtures ensure forming a score line of adequate thickness,
      shape, size, curvature. According to the obtained results, this type of extended
      release formulation is eligible for splitting and use in therapy either as a
      whole or scored tablets.

PMID- 19754483
TI  - Angina pectoris and physiological coronarographic findings.
AB  - Angina pectoris may be associated with normaln coronary arteries. Normal coronary
      arteries status is defined as absence of visible disease or the irregularity of
      lumen (less than 50%) as assessed visually on the interventional cardiologists.
      In our retrospective study among 1130 patients we have identified 181 patients
      with normal angiographic findings with various risk factors, as male sex, body
      mass index (BMI), lipid disorders, smoking, hypertension, diabetes mellitus type
      2. The analysis results suggest that 56.3% patients of 181 verified normal
      coronary findings involve female patients with high BMI, unregulated hypertension
      and lipid disorders. In order to find real causes of chest pain, patients with
      normal coronary status need careful examination and treatment. The reduction of
      risk factors and adequate medications are important preconditions for the good
      quality of life in these patients.

PMID- 19754484
TI  - The rules of engagement.

PMID- 19754485
TI  - Religious practice, blood transfusion, and major medical procedures.
AB  - In this debate, we explore the dilemmas between the law, the ethical issues, the
      good clinical practice, and the wishes of the family. In the scenario chosen, the
      issues center around not only the senior family members but also of an older
      child with some rights to self-determination. There are no absolute rights or
      wrongs to this case, which is based on a synthesis of other actual clinical
      scenarios. The maze of considerations are not easy to negotiate, and in the final
      analysis, the surgeon and the anesthetist must also be comfortable with the
      decisions as they are the active elements that have to practically manage a
      clinical crisis should it occur. The participants in this debate are all UK
      based, and as such the legal standpoint reflects UK legislation, and the ethical
      and clinical reviews are strongly influenced by current attitudes within UK and
      Europe that may not be exactly mirrored in different cultural frameworks.
      However, in this article, it is the broad principles behind the differing
      responses that are important, which it is hoped will stimulate reflection of
      attitudes and management in different cultural frameworks.

PMID- 19754486
TI  - Ethical concerns in the management of pain in the neonate.
AB  - The debate about the management of pain in the neonate has continued to evolve
      over the past 30 years. This controversy can be understood as evolving through
      now three eras of thought about the effect of pain and its management in newborns
      and infants. The first generation was characterized by a widespread belief that
      newborns lacked the complete development of the neuroanatomical and
      neuroendocrine components necessary to perceive pain. During this period,
      newborns often received inadequate anesthesia and analgesia for painful
      procedures, if not no treatment at all. The second generation was heralded by
      research that demonstrated that newborns did demonstrate similar or even
      exaggerated physiological and hormonal responses to pain compared with those
      observed in older children and adults and that exposure to prolonged or severe
      pain may increase neonatal morbidity. Controversy in this generation focused
      around the dosage of analgesia to newborns as well as the risks and benefits of
      pain management techniques. We are now in a third generation of thought about
      pain in the neonate, defined by intense debate over the significance of a growing
      number of studies in immature animal models that demonstrate degenerative effects
      of several anesthetics on neuronal structure. The challenge of this era is to
      integrate the advances in diagnosis and treatment achieved in previous
      generations with ongoing adaptation of clinical practice as dictated by research
      advances in the field. In this review, we examine the evolution of medical
      thought and ethical concerns regarding pain treatment in the neonate.

PMID- 19754487
TI  - Withholding and withdrawing life-sustaining treatment in children.
AB  - Modern medicine gives us the ability to prolong life even in situations where it
      may not be right to do so. This article discusses some of the complex ethical and
      legal issues surrounding withholding and withdrawing life-sustaining treatment in
      children, including the concepts of futility, best interests and intolerability.
      We advocate the use of a structured framework to help guide decision-making,
      particularly in the more difficult situations. The lack of a morally or legally
      significant difference between withholding and withdrawing treatment is
      discussed, as is the role of the doctrine of double effect (particularly in
      relation to the use of neuromuscular blocking agents during withdrawal of
      ventilatory support).

PMID- 19754488
TI  - Safeguarding children: why an issue for pediatric anesthetists?
AB  - Child maltreatment and the responsibility of heath care professionals to assist
      in prevention and diagnosis is currently center stage in the United Kingdom. This
      subject has a very large literature base. Anesthetists were one of the first
      groups to have specific guidance on this subject, and key competencies are now
      part of the core curriculum for our trainees. This article seeks to briefly
      define maltreatment and provide statistics that outline the scale of the problem,
      and includes discussion of risk factors and recognition. We have focused on
      physical abuse and have provided a separate section on abusive head trauma, which
      is of particular importance to anesthetists. We also discuss the process of
      management, with some detail around Child Death Review procedures.

PMID- 19754489
TI  - The Runaway Child: managing anticipatory fear, resistance and distress in
      children undergoing surgery.

PMID- 19754490
TI  - Comparison of the On-Q Painbuster Post-Op Pain Relief System to a thoracic
      epidural for control of postoperative thoracotomy pain in a child.

PMID- 19754491
TI  - Anesthetic implications of Danon disease.

PMID- 19754492
TI  - The new air-Q intubating laryngeal airway for tracheal intubation in children
      with anticipated difficult airway: comment.

PMID- 19754494
TI  - Congenital tracheal stenosis managed with external chest compression exhalation
      technique for acute airway obstruction relief.

PMID- 19754495
TI  - Successful intubation using a simple fiberoptic assisted laryngoscope for
      Treacher Collins syndrome.
AB  - A fiberoptic-assisted laryngoscope (FLS) (Acoma Medical Industry Co. Ltd., Tokyo,
      Japan) is a modified Macintosh laryngoscope with a tubular holder into which a
      fiberoptic bronchoscope can be inserted. We present three cases of Treacher
      Collins syndrome whose tracheas were successfully intubated with the aid of the
      FLS. These cases suggest that the FLS may be a useful alternative in the case of
      difficult pediatric intubation.

PMID- 19754497
TI  - Influence of age on the association between various measures of obesity and all
      cause mortality.
AB  - OBJECTIVES: To determine whether the association between various simple measures
      of obesity and risk for all-cause mortality differs between younger and older men
      and women. DESIGN: Prospective cohort study with 8.7 +/- 0.2 years of follow-up
      for mortality linkage. SETTING: Third National Health and Nutrition Examination
      Survey, 1988 to 1994. PARTICIPANTS: Four thousand, four hundred thirty-seven men
      and 5,166 women. MEASUREMENTS: Measures of obesity included body mass, waist
      circumference, waist-to-hip ratio, hip circumference, sum of skinfolds, and
      bioelectrical impedance. RESULTS: Overall and abdominal obesity are associated
      with greater mortality risk in younger adults (<65) (P<.05), whereas the
      associations between obesity and mortality are null or inverse in older adults
      (>65). In general, the association was stronger with measures of abdominal
      obesity than with measures of overall obesity or fat-free mass. CONCLUSION: The
      adverse effects of obesity on mortality risk are apparent only in adults younger
      than 65. Obesity as characterized using several different measures was not
      generally associated with greater mortality risk in older adults. Although weight
      loss is beneficial for reducing morbidity in obese adults of any age, it is
      unclear whether weight loss is equally beneficial for reducing mortality risk in
      older adults.

PMID- 19754498
TI  - An intervention integrated into daily clinical practice reduces the incidence of
      delirium during hospitalization in elderly patients.
AB  - OBJECTIVES: To analyze the effectiveness of a multicomponent intervention
      integrated into daily practice for the prevention of in-hospital delirium in
      elderly patients. DESIGN: Controlled study comparing an intervention in a
      geriatric unit (GI) with usual care in two internal medicine services (UC).
      SETTING: University hospital in Madrid, Spain. PARTICIPANTS: Five hundred forty
      two consecutive patients (170 GI, 372 UC), aged 70 and older, with any of the
      risk criteria for delirium (cognitive impairment, visual impairment, acute
      disease severity, dehydration). INTERVENTION: Educational measures and specific
      actions in seven risk areas (orientation, sensory impairment, sleep,
      mobilization, hydration, nutrition, drug use). Daily monitoring of adherence.
      MEASUREMENTS: Baseline characteristics, risk factors for delirium, and quality
      care indicators were analyzed. The primary endpoint was incidence of delirium
      assessed daily. The secondary endpoint was functional decline, defined as loss of
      independence in any of the activities of daily living. The intervention effect
      was evaluated using logistic regression analysis. RESULTS: Delirium affected
      11.7% of the GI group and 18.5% of the UC group (P=.04). After adjustment for
      confounders, the intervention was associated with lower incidence of delirium
      (odds ratio=0.4, 95% confidence interval=0.24-0.77; P=.005). In the patients who
      experienced delirium, severity, length, and recurrence of episodes were similar
      in both groups. Adherence to the intervention protocols was 75.7%. The
      intervention reduced the rate of functional decline (45.5% in GI vs 56.3% in UC,
      P=.03) and improved other quality indicators (e.g., mobilization and physical
      restraints reduction). CONCLUSION: A multicomponent, nonpharmacological
      intervention integrated into routine practice reduces delirium during
      hospitalization in older patients, improves quality of care, and can be
      implemented without additional resources in a public healthcare system.

PMID- 19754499
TI  - Age and persistent use of cardiovascular medication after acute coronary
      syndrome: results from medication applied and sustained over time.
AB  - OBJECTIVES: To describe the persistent use of evidence-based cardiovascular
      medications (EBCMs) 3 months after discharge from an acute coronary syndrome
      (ACS) event and patient-reported reasons for nonpersistence across age groups.
      DESIGN: Medication Applied and Sustained Over Time (MAINTAIN) is a longitudinal
      follow-up cohort study of the Can Rapid Risk Stratification of Unstable Angina
      Patients Suppress ADverse Outcomes with Early Implementation quality improvement
      initiative and Acute Coronary Treatment and Intervention Outcomes Network
      registry. SETTING: Forty-one acute care hospitals in the United States from
      January 2006 to September 2007. PARTICIPANTS: One thousand fifty-four patients
      with a median age of 60 (interquartile range 52-71), including 27% aged 70 and
      older, admitted with an ACS. MEASUREMENTS: Three-month posthospital discharge
      telephone follow-up with EBCMs reviewed and reconciled. Patients who reported
      nonpersistence were surveyed regarding reasons for EBCM discontinuation. RESULTS:
      At 3-month follow-up, overall persistence was 71.2%. There was a significant
      trend toward lower overall persistence with prescribed EBCMs in older adults than
      in the other age groups (74.9% for <60, 71.0% for 60-69, 64.5% for > or =70;
      P=.02). Overall, 112 (10.6%) patients discontinued EBCMs with provider advice,
      and 178 (16.9%) self-discontinued. Provider discontinuation increased across age
      groups (9.1%, 10.4%, and 13.6%, respectively). A similar trend was observed for
      EBCM self-discontinuation (15.2%, 17.0%, and 19.9%, respectively). Reasons for
      self-discontinuation included adverse effects, cost, and perception that the
      medication was not needed. CONCLUSION: Older patients are less likely to be
      persistent with EBCMs after an ACS event at 3-month follow-up. Understanding
      patient-reported reasons for discontinuation can influence intervention
      strategies to improve long-term adherence to EBCMs.

PMID- 19754500
TI  - Neighborhood deprivation, individual socioeconomic status, and frailty in older
      adults.
AB  - OBJECTIVES: To assess how individual socioeconomic status and neighborhood
      deprivation affect frailty. DESIGN: Nationally representative population-based
      study, the English Longitudinal Study of Aging (ELSA), analyzed cross
      sectionally. PARTICIPANTS: Four thousand eight hundred eighteen individuals aged
      65 and older. MEASUREMENTS: Outcome was a frailty index (FI), based on 58
      potential deficits, with a theoretical range from 0 to 1; exposures were
      individual wealth and neighborhood deprivation (lack of local resources,
      financial and otherwise), based on a set of standard indicators. RESULTS: The FI
      score varied independently according to wealth and neighborhood deprivation. The
      mean FI score for an individual in the highest 20% of wealth and least deprived
      20% of neighborhoods was 0.09 (95% confidence interval (CI)=0.09-0.09) and for an
      individual in the lowest 20% of wealth and most deprived 20% of neighborhoods was
      0.17 (95% CI=0.16-0.17). CONCLUSION: Frailty in older adults is independently
      associated with individual and neighborhood socioeconomic factors. Older adults
      who are poor and live in deprived neighborhoods are most vulnerable. Policies and
      interventions intended to prevent or reduce frailty must take into account
      individual circumstances and the broader social settings in which individuals are
      located.

PMID- 19754501
TI  - The late positive potential: a neurophysiological marker for emotion regulation
      in children.
AB  - BACKGROUND: The ability to modulate emotional responses, or emotion regulation,
      is a key mechanism in the development of mood disruptions. Detection of a neural
      marker for emotion regulation thus has the potential to inform early detection
      and intervention for mood problems. One such neural marker may be the late
      positive potential (LPP), which is a scalp-recorded event-related potential
      reflecting facilitated attention to emotional stimuli. In adults, the LPP is
      reduced following use of cognitive emotion regulation strategies such as
      reappraisal. No studies to date have examined the LPP in relation to cognitive
      emotion regulation in children, and whether the LPP is related to parent-report
      measures of emotion regulation and mood disruptions. METHODS: To examine this
      question, high-density electroencephalograph (EEG) was recorded from 20 children
      (M age = 87.8 months, SD = 18.02; 10 girls) while they viewed unpleasant
      emotional pictures following either a directed negative or neutral interpretation
      of the picture. RESULTS: As predicted, the LPP was smaller following neutral
      versus negative interpretations at posterior recording sites, except for younger
      girls (aged 5-6). The timing of this effect was later than that reported in
      studies with adults. For all children, greater modulation of the LPP by neutral
      interpretations was associated with reduced anxious-depressed symptoms, whereas
      larger LPPs for both interpretation types were associated with greater mood
      symptoms and worse parent-reported emotion regulation. CONCLUSIONS: Results
      suggest that the LPP may represent a clinically relevant neural marker for
      emotion regulation and mood disruptions.

PMID- 19754502
TI  - Deficits in interval timing measured by the dual-task paradigm among children and
      adolescents with attention-deficit/hyperactivity disorder.
AB  - BACKGROUND: The underlying mechanism of time perception deficit in long time
      intervals in attention-deficit/hyperactivity disorder (ADHD) is still unclear.
      This study used the time reproduction dual task to explore the role of the
      attentional resource in time perception deficits among children and adolescents
      with ADHD. METHODS: Participants included 168 children and adolescents with DSM
      IV ADHD and 90 control children and adolescents without ADHD, aged 10 to 17
      years, in Taipei. The DSM-IV diagnoses of ADHD and other psychiatric comorbid
      conditions were made by clinical assessments and confirmed by the psychiatric
      interviews of both parents and participants using the Chinese Kiddie
      Epidemiologic version of the Schedule for Affective Disorders and Schizophrenia.
      The participants were also assessed by using the Wechsler Intelligence Scale for
      Children-3(rd) edition (WISC-III), and time reproduction tasks (the single task
      and the simple and difficult versions of the dual tasks) at 5-second, 12-second,
      and 17-second intervals. The linear mixed model was used for data analysis.
      RESULTS: Children and adolescents with ADHD had less precise time reproduction
      than the controls in all three tasks except the 5-second interval of the single
      task. There were significant interactions between group and interval (12-second
      vs. 5-second, p = .030; 17-second vs. 5-second, p < .001), and between group and
      task (simple dual task vs. single task, p = .016; difficult dual task vs. single
      task, p < .001) after controlling for FSIQ, comorbidity, sex, age, use of
      methylphenidate, and the performance of the non-temporal tasks in dual tasks, if
      relevant. CONCLUSIONS: Significantly increased estimation errors in ADHD with
      increased task difficulties suggest that impaired timing processing in children
      and adolescents with ADHD during long time intervals may be accounted for by the
      limited attentional capacity rather than a primary problem in timing per se. This
      finding does not apply to rapid time intervals, in which cerebellar circuitry is
      important.

PMID- 19754503
TI  - Practitioner review: When parent training doesn't work: theory-driven clinical
      strategies.
AB  - Improving the parent-child relationship by using strategies based on social
      learning theory has become the cornerstone for the treatment of conduct problems
      in children. Over the past 40 years, interventions have expanded greatly from
      small, experimental procedures to substantial, systematic programmes that provide
      clear guidelines in detailed manuals on how practitioners should implement the
      standardised treatments. They are now widely disseminated and there is a great
      deal of empirical support that they are very effective for the majority of cases.
      However, evaluations of even the best of these evidence-based programmes show
      that a quarter to a third of families and their children do not benefit. What
      does the practitioner then do, when a standard social learning approach,
      diligently applied, doesn't work? We argue that under these circumstances, some
      of the major theories of child development, family functioning and individual
      psychology can help the skilled practitioner think his or her way through complex
      clinical situations. This paper describes a set of practical strategies that can
      then be flexibly applied, based on a systematic theoretical analysis. We hold
      that social learning theory remains the core of effective parent training
      interventions, but that ideas from attachment theory, structural family systems
      theory, cognitive-attribution theory, and shared empowerment/motivational
      interviewing can each, according to the nature of the difficulty, greatly enrich
      the practitioner's ability to help bring about change in families who are stuck.
      We summarise each of these models and present practical examples of when and how
      they may help the clinician plan treatment.

PMID- 19754504
TI  - Pulmonary artery intimal sarcoma: case report.
AB  - A 72-year-old woman with pulmonary artery intimal sarcoma was successfully
      treated with surgery. With heightened clinical awareness and technological
      advancement, more and more cases were diagnosed definitely before operation.
      Computed tomography of the chest showed a mass in right ventricular extending to
      pulmonary trunk and the left pulmonary artery. The patient underwent complete
      surgical resection and repair of the pulmonary artery with no evidence of
      recurrence during the 12-month follow-up, suggesting that early identification
      and aggressive surgical intervention would improve survival.

PMID- 19754505
TI  - Parallel evolution in the major haemoglobin genes of eight species of Andean
      waterfowl.
AB  - Theory predicts that parallel evolution should be common when the number of
      beneficial mutations is limited by selective constraints on protein structure.
      However, confirmation is scarce in natural populations. Here we studied the major
      haemoglobin genes of eight Andean duck lineages and compared them to 115 other
      waterfowl species, including the bar-headed goose (Anser indicus) and Abyssinian
      blue-winged goose (Cyanochen cyanopterus), two additional species living at high
      altitude. One to five amino acid replacements were significantly overrepresented
      or derived in each highland population, and parallel substitutions were more
      common than in simulated sequences evolved under a neutral model. Two
      substitutions evolved in parallel in the alpha A subunit of two (Ala-alpha 8) and
      five (Thr-alpha 77) taxa, and five identical beta A subunit substitutions were
      observed in two (Ser-beta 4, Glu-beta 94, Met-beta 133) or three (Ser-beta 13,
      Ser-beta 116) taxa. Substitutions at adjacent sites within the same functional
      protein region were also observed. Five such replacements were in exterior,
      solvent-accessible positions on the A helix and AB corner of the alpha A subunit.
      Five others were in close proximity to inositolpentaphosphate binding sites, and
      two pairs of independent replacements occurred at two different alpha(1)beta(1)
      intersubunit contacts. More than half of the substitutions in highland lineages
      resulted in the acquisition of serine or threonine (18 gains vs. 2 losses), both
      of which possess a hydroxyl group that can hydrogen bond to a variety of polar
      substrates. The patterns of parallel evolution observed in these waterfowl
      suggest that adaptation to high-altitude hypoxia has resulted from selection on
      unique but overlapping sets of one to five amino acid substitutions in each
      lineage.

PMID- 19754506
TI  - The allopolyploid Arabidopsis kamchatica originated from multiple individuals of
      Arabidopsis lyrata and Arabidopsis halleri.
AB  - Polyploidization, or genome duplication, has played a critical role in the
      diversification of animals, fungi and plants. Little is known about the
      population structure and multiple origins of polyploid species because of the
      difficulty in identifying multiple homeologous nuclear genes. The allotetraploid
      species Arabidopsis kamchatica is closely related to the model species
      Arabidopsis thaliana and is distributed in a broader climatic niche than its
      parental species. Here, we performed direct sequencing of homeologous pairs of
      the low-copy nuclear genes WER and CHS by designing homeolog-specific primers,
      and obtained also chloroplast and ribosomal internal transcribed spacer
      sequences. Phylogenetic analysis showed that 50 individuals covering the
      distribution range including North America are allopolyploids derived from
      Arabidopsis lyrata and Arabidopsis halleri. Three major clusters within A.
      kamchatica were detected using Bayesian clustering. One cluster has widespread
      distribution. The other two are restricted to the southern part of the
      distribution range including Japan, where the parent A. lyrata is not currently
      distributed. This suggests that the mountains in Central Honshu and surrounding
      areas in Japan served as refugia during glacial-interglacial cycles and retained
      this diversity. We also found that multiple haplotypes of nuclear and chloroplast
      sequences of A. kamchatica are identical to those of their parental species. This
      indicates that multiple diploid individuals contributed to the origin of A.
      kamchatica. The haplotypes of low-copy nuclear genes in Japan suggest independent
      polyploidization events rather than introgression. Our findings suggest that self
      compatibility and gene silencing occurred independently in different origins.

PMID- 19754507
TI  - Population genetic analysis reveals a homoploid hybrid origin of Stephanomeria
      diegensis (Asteraceae).
AB  - Homoploid hybrid speciation has generally been viewed as a rare evolutionary
      phenomenon, with relatively few well-documented cases in nature. Here, we
      investigate the origin of Stephanomeria diegensis, a diploid flowering plant
      species that has been proposed to have arisen as a result of hybridization
      between S. exigua and S. virgata. Across the range of S. diegensis, all
      individuals share a common chloroplast haplotype with S. virgata while showing a
      greater affinity for S. exigua in terms of nuclear genetic diversity. A principal
      coordinates analysis (PCO) based on the nuclear data revealed that S. diegensis
      is most similar to each parent along different axes. Moreover, a Bayesian
      clustering analysis as well as a hybrid index-based analysis showed evidence of
      mixed ancestry, with approximately two thirds of the S. diegensis nuclear genome
      derived from S. exigua. These results provide strong support for a homoploid
      hybrid origin of S. diegensis. Finally, contrary to the finding that homoploid
      hybrid species are typically multiply-derived, our results were most consistent
      with a single origin of this species.

PMID- 19754508
TI  - Do insects lose flight before they lose their wings? Population genetic structure
      in subalpine stoneflies.
AB  - Wing reduction and flightlessness are common features of alpine and subalpine
      insects, and are typically interpreted as evolutionary adaptations to increase
      fecundity and promote local recruitment. Here, we assess the impact of wing
      reduction on dispersal in stoneflies (Plecoptera: Gripopterygidae: Zelandoperla)
      in southern New Zealand. Specifically, we present comparative phylogeographic
      analyses (COI; H3) of strong-flying Zelandoperla decorata (144 individuals, 63
      localities) vs. the co-distributed but weak-flying Zelandoperla fenestrata
      species group (186 individuals, 81 localities). The latter group exhibits a
      variety of morphotypes, ranging from fully winged to completely wingless.
      Consistent with its capacity for strong flight-mediated dispersal, Z. decorata
      exhibited no substantial phylogeographic differentiation across its broad South
      Island range. Conversely the weak-flying fenestrata species group exhibited
      substantial genetic structure across both fine and broad geographic scales.
      Intriguingly, the variable degrees of wing development observed within the
      fenestrata species group had no apparent impact on levels of phylogeographic
      structure, which were high regardless of morphotype, suggesting that even fully
      winged specimens of this group do not fly. This finding implies that Zelandoperla
      flight loss occurs independently of wing loss, and might reflect underlying
      flight muscle reduction.

PMID- 19754509
TI  - Erratum. How few whales were there after whaling? Inference from contemporary
      mtDNA diversity.How few whales were there after whaling? Inference from
      contemporary mtDNA diversity.

PMID- 19754510
TI  - Case studies and mathematical models of ecological speciation. 3: Ecotype
      formation in a Swedish snail.
AB  - Formation of partially reproductively isolated ecotypes in the rough periwinkle,
      Littorina saxatilis, may be a case of incipient nonallopatric ecological
      speciation. To better understand the dynamics of ecotype formation, its
      timescale, driving forces and evolutionary consequences, we developed a spatially
      explicit, individual-based model incorporating relevant ecological, spatial and
      mate selection data for Swedish L. saxatilis. We explore the impact of bounded
      hybrid superiority, ecological scenarios and mate selection systems on ecotype
      formation, gene flow and the evolution of prezygotic isolation. Our model shows
      that ecotypes are expected to form rapidly in parapatry under conditions
      applicable to Swedish L. saxatilis and may proceed to speciation. However,
      evolution of nonrandom mating had complex behaviour. Ecotype evolution was
      inhibited by pre-existing mating preferences, but facilitated by the evolution of
      novel preferences. While in many scenarios positive assortative mating reduced
      gene flow between ecotypes, in others negative assortative mating arose,
      preferences were lost after ecotype formation, preferences were confined to one
      ecotype or the ancestral ecotype became extinct through sexual selection. Bounded
      hybrid superiority (as observed in nature) enhanced ecotype formation but
      increased gene flow. Our results highlight that ecotype formation and speciation
      are distinct processes: factors that contribute to ecotype formation can be
      detrimental to speciation and vice versa. The complex interactions observed
      between local adaptation and nonrandom mating imply that generalization from data
      is unreliable without quantitative theory for speciation.

PMID- 19754511
TI  - Power and sample size for nested analysis of molecular variance.
AB  - Analysis of molecular variance (AMOVA) is a widely used tool for quantifying the
      contribution of various levels of population structure to patterns of genetic
      variation. Implementations of AMOVA use permutation tests to evaluate null
      hypotheses of no population structure within groups and between groups. With few
      populations per group, between-group structure might be impossible to detect
      because only a few permutations of the sampled populations are possible. In fact,
      with fewer than six total populations, permutation tests will never result in P
      values <0.05 for higher-level population structure. I present minimum numbers of
      replicates calculated from multinomial coefficients and an r script that can be
      used to evaluate the minimum P-value for any sampling scheme. While it might seem
      counterintuitive that a large sample of individuals is uninformative about
      hierarchical structure, the power to detect between-group differences depends on
      the number of populations per group and investigators should sample
      appropriately.

PMID- 19754512
TI  - Morphology and nuclear markers reveal extensive mitochondrial introgressions in
      the Iberian Wall Lizard species complex.
AB  - Mitochondrial markers are still often used alone to identify evolutionary units,
      despite widespread evidence for processes such as incomplete lineage sorting or
      introgressive hybridization that may blur past population history. The
      combination of mitochondrial DNA data with other sources of information
      (morphology, nuclear genes) is a powerful tool to reveal when and why
      mitochondrial markers are potentially misleading. In this study, we evaluate the
      performance of mtDNA markers to unravel the evolutionary history of Spanish
      lizards from the Podarcis hispanicus species complex. We first uncover several
      cases of discordance between morphological and mitochondrial data in delimitation
      of taxa. To assess the origin of these discordances, we analysed the same
      populations using several independent nuclear loci. Both morphological and
      nuclear markers identified the same three evolutionary units in the region, while
      mitochondrial data revealed four deeply divergent lineages. We suggest here that
      the most likely scenario to explain this discordance is ancient mitochondrial
      introgression originating from a fourth evolutionary unit presently absent from
      the study area. Notably, this resulted in a complete replacement of the original
      lineage in a large part of the distribution of one of the taxa investigated. We
      discuss the potential evolutionary scenarios leading to this complete
      mitochondrial replacement and suggest why the previous studies have failed to
      recover the correct history of this species complex.

PMID- 19754513
TI  - Prevalence and diversity patterns of avian blood parasites in degraded African
      rainforest habitats.
AB  - Land use changes including deforestation, road construction and agricultural
      encroachments have been linked to the increased prevalence of several infectious
      diseases. In order to better understand how deforestation affects the prevalence
      of vector-borne infectious diseases in wildlife, nine paired sites were sampled
      (disturbed vs. undisturbed habitats) in Southern Cameroon. We studied the
      diversity, prevalence and distribution of avian malaria parasites (Plasmodium
      spp.) and other related haemosporidians (species of Haemoproteus and
      Leucocytozoon) from these sites in two widespread species of African rainforest
      birds, the yellow-whiskered greenbul (Andropadus latirostris, Pycnonotidae) and
      the olive sunbird (Cyanomitra olivacea, Nectariniidae). Twenty-six mitochondrial
      cytochrome b lineages were identified: 20 Plasmodium lineages and 6 Haemoproteus
      lineages. These lineages showed no geographic specificity, nor significant
      differences in lineage diversity between habitat types. However, we found that
      the prevalence of Leucocytozoon and Haemoproteus infections were significantly
      higher in undisturbed than in deforested habitats (Leucocytozoon spp. 50.3% vs.
      35.8%, Haemoproteus spp. 16.3% vs. 10.8%). We also found higher prevalence for
      all haemosporidian parasites in C. olivacea than in A. latirostris species (70.2%
      vs. 58.2%). Interestingly, we found one morphospecies of Plasmodium in C.
      olivacea, as represented by a clade of related lineages, showed increased
      prevalence at disturbed sites, while another showed a decrease, testifying to
      different patterns of transmission, even among closely related lineages of avian
      malaria, in relation to deforestation. Our work demonstrates that anthropogenic
      habitat change can affect host-parasite systems and result in opposing trends in
      prevalence of haemosporidian parasites in wild bird populations.

PMID- 19754514
TI  - Molecular insights into the colonization and chromosomal diversification of
      Madeiran house mice.
AB  - The colonization history of Madeiran house mice was investigated by analysing the
      complete mitochondrial (mt) D-loop sequences of 156 mice from the island of
      Madeira and mainland Portugal, extending on previous studies. The numbers of
      mtDNA haplotypes from Madeira and mainland Portugal were substantially increased
      (17 and 14 new haplotypes respectively), and phylogenetic analysis confirmed the
      previously reported link between the Madeiran archipelago and northern Europe.
      Sequence analysis revealed the presence of four mtDNA lineages in mainland
      Portugal, of which one was particularly common and widespread (termed the
      'Portugal Main Clade'). There was no support for population bottlenecks during
      the formation of the six Robertsonian chromosome races on the island of Madeira,
      and D-loop sequence variation was not found to be structured according to
      karyotype. The colonization time of the Madeiran archipelago by Mus musculus
      domesticus was approached using two molecular dating methods (mismatch
      distribution and Bayesian skyline plot). Time estimates based on D-loop sequence
      variation at mainland sites (including previously published data from France and
      Turkey) were evaluated in the context of the zooarchaeological record of M. m.
      domesticus. A range of values for mutation rate (mu) and number of mouse
      generations per year was considered in these analyses because of the uncertainty
      surrounding these two parameters. The colonization of Portugal and Madeira by
      house mice is discussed in the context of the best-supported parameter values. In
      keeping with recent studies, our results suggest that mutation rate estimates
      based on interspecific divergence lead to gross overestimates concerning the
      timing of recent within-species events.

PMID- 19754515
TI  - Relative contribution of contemporary pollen and seed dispersal to the effective
      parental size of seedling population of California valley oak (Quercus lobata,
      Nee).
AB  - For plant populations, gene movement through pollen and seed dispersal governs
      the size of local genetic neighbourhoods and shapes the opportunities for natural
      selection and genetic drift. A critical question is how together these two
      processes influence the evolutionary dynamics of local populations. To assess the
      respective contributions of pollen and seed flow, we propose a novel indirect
      assessment of the separate male and female gametic contributions to total
      effective parental size (N(e)), based on parental correlations estimated via
      kinship coefficients, that can be applied to data sets that include unambiguous
      genotypes for male and female gametic contributions. Using the endemic
      Californian valley oak (Quercus lobata) as our study species, we apply this
      method to a set of microsatellite genotypes for two distinct ecological sets of
      naturally recruiting seedlings with acorns attached. We found that the effective
      numbers of contributing male parents (N(ep)) exceed effective numbers of female
      parents (N(em)) for seedlings established beneath adult trees (N(ep) = 8.1 and
      N(em) = 1.1), as well as for seedlings established away from adult trees (N(ep) =
      15.4 and N(em) = 2.7), illustrating that seed dispersal enhances pollen dispersal
      and increases the effective number of seed sources in open seedling patches. The
      resulting effective parental size of seedling populations translates into smaller
      effective numbers of parents for undispersed vs. dispersed seedlings (N(e) = 3.6
      and N(e) = 6.7, respectively). This study introduces a novel statistic method and
      provides important new evidence that, on a short-term temporal scale, seed
      dispersal shapes the local neighbourhood size of new recruits.

PMID- 19754516
TI  - Phylogenetic endemism: a new approach for identifying geographical concentrations
      of evolutionary history.
AB  - We present a new, broadly applicable measure of the spatial restriction of
      phylogenetic diversity, termed phylogenetic endemism (PE). PE combines the widely
      used phylogenetic diversity and weighted endemism measures to identify areas
      where substantial components of phylogenetic diversity are restricted. Such areas
      are likely to be of considerable importance for conservation. PE has a number of
      desirable properties not combined in previous approaches. It assesses endemism
      consistently, independent of taxonomic status or level, and independent of
      previously defined political or biological regions. The results can be directly
      compared between areas because they are based on equivalent spatial units. PE
      builds on previous phylogenetic analyses of endemism, but provides a more general
      solution for mapping endemism of lineages. We illustrate the broad applicability
      of PE using examples of Australian organisms having contrasting life histories:
      pea-flowered shrubs of the genus Daviesia (Fabaceae) and the Australian species
      of the Australo-Papuan tree frog radiation within the family Hylidae.

PMID- 19754517
TI  - Range persistence during the last glacial maximum: Carex macrocephala was not
      restricted to glacial refugia.
AB  - The distribution of many species inhabiting northwestern North America has been
      heavily influenced by the climatic changes during the late Pleistocene. Several
      studies have suggested that species were restricted to glacial refugia north
      and/or south of the continental ice sheet front. It is also hypothesized that the
      coast of northwestern North America could have been a prime location for glacial
      refugia because of the lowering of the eustatic sea level and the concomitant
      rise of the continental shelf because of tectonic rebound. Alternatively, some
      coastal species distributions and demographics may have been unaffected in the
      long-term by the last glacial maximum (LGM). We tested the glacial refugium
      hypothesis on an obligate coastal plant species, Carex macrocephala by sampling
      600 individuals from 41 populations with 11 nuclear microsatellite loci and the
      rpL16 plastid intragenic spacer region. The microsatellite data sets suggest a
      low level of population differentiation with a standardized G'(ST) = 0.032 and
      inbreeding was high with an F = 0.969. The homogenization of the populations
      along the coast was supported by a principal coordinate analysis, amovas and
      samova analyses. Analyses using the rpL16 data set support the results of the
      microsatellite analyses, with a low F(ST) of 0.042. Coalescent and mismatch
      analyses using rpL16 suggest that C. macrocephala has not gone through a
      significant bottleneck within the past 100,000 years, although a much earlier
      population expansion was indicated by the mismatch analysis. Carex macrocephala
      exhibits the characteristics of metapopulation dynamics and on the basis of these
      results, we concluded that it was not restricted to glacial refugia during the
      LGM, but that it existed as a large metapopulation.

PMID- 19754518
TI  - The upstream open reading frame of the Arabidopsis AtMHX gene has a strong impact
      on transcript accumulation through the nonsense-mediated mRNA decay pathway.
AB  - Approximately 20% of plant genes possess upstream open-reading frames (uORFs).
      The effect of uORFs on gene expression has mainly been studied at the
      translational level. Very little is known about the impact of plant uORFs on
      transcript content through the nonsense-mediated mRNA decay (NMD) pathway, which
      degrades transcripts bearing premature termination codons (PTCs). Here we examine
      the impact of the uORF of the Arabidopsis AtMHX gene on transcript accumulation.
      The suggestion that this uORF exposes transcripts containing it to NMD is
      supported by (i) the increase in transcript levels upon eliminating the uORF from
      constructs containing it, (ii) experiments with a modified uORF-peptide, which
      excluded peptide-specific degradation mechanisms, (iii) the increase in levels of
      the native AtMHX transcript upon treatment with cycloheximide, which inhibits
      translation and blocks NMD, and (iv) the sensitivity of transcripts containing
      the uORF of AtMHX to the presence of introns. We also showed that introns can
      increase NMD efficiency not only in transcripts having relatively short 3'
      untranslated regions (UTRs), but also in uORF-containing transcripts. AtMHX
      transcript levels were almost unaltered in mutants of the NMD factors UPF3 and
      UPF1. Possible reasons, including the existence of a NMD-compensatory mechanism,
      are discussed. Interestingly, the levels of UPF3 transcript were higher in upf1
      mutants, suggesting a compensatory mechanism that links weak function of the NMD
      machinery to increased expression of UPF3. Our findings highlight that uORFs,
      which are abundant in plants, can not only inhibit translation but also strongly
      affect transcript accumulation.

PMID- 19754519
TI  - Targeted proteomics using selected reaction monitoring reveals the induction of
      specific terpene synthases in a multi-level study of methyl jasmonate-treated
      Norway spruce (Picea abies).
AB  - Induction of terpene synthase (TPS) gene expression and enzyme activity is known
      to occur in response to various chemical and biological stimuli in several
      species of spruce (genus Picea). However, high sequence identity between TPS
      family members has made it difficult to determine the induction patterns of
      individual TPS at the protein and transcript levels and whether specific TPS
      enzymes respond differentially to treatment. In the present study we used a multi
      level approach to measure the induction and activity of TPS enzymes in protein
      extracts of Norway spruce (Picea abies) bark tissue following treatment with
      methyl jasmonate (MeJA). Measurements were made on the transcript, protein,
      enzyme activity and metabolite levels. Using a relatively new proteomics
      application, selective reaction monitoring (SRM), it was possible to
      differentiate and quantitatively measure the abundance of several known TPS
      proteins and three 1-deoxy-D-xylulose 5-phosphate synthase (DXS) isoforms in
      Norway spruce. Protein levels of individual TPS and DXS enzymes were
      differentially induced upon MeJA treatment and good correlation was generally
      observed between induction of transcripts, proteins, and enzyme activities. Most
      of the mono- and diterpenoid metabolites accumulated with similar temporal
      patterns of induction as part of the coordinated multi-compound chemical defense
      response. Protein and enzyme activity levels of the monoTPS (+)-3-carene synthase
      and the corresponding accumulation of (+)-3-carene was induced to a higher fold
      change than any other TPS or metabolite measured, indicating an important role in
      the induced terpenoid defense response in Norway spruce.

PMID- 19754520
TI  - Availability of essential medicines in Ethiopia: an efficiency-equity trade-off?
AB  - OBJECTIVE: To investigate the availability and cost of essential medicines in
      health centres in rural Ethiopia, and to explore if the fee waiver system
      protects patients from having to pay for medicines. METHODS: The study took place
      in five health centres in rural Ethiopia. Availability and price of selected key
      essential medicines was established in the budget and special pharmacy of the
      health centre, as well as private outlets. Information on availability and cost
      of prescribed drugs was obtained through patient exit-interviews. RESULTS:
      Availability based of essential drugs at facility level was 91% based on a list
      of selected drugs vs. 84% based on prescriptions filled. However, less than half
      the prescribed drugs were obtained from the budget pharmacy, and one in six
      patients was forced to purchase drugs in the private sector, where drugs are
      roughly twice as expensive. The waiver system did not safeguard against having to
      pay for medicines. CONCLUSION: A revolving drug fund system in Ethiopia seems to
      improve availability of medicines, and can improve affordability by protecting
      people from purchasing drugs in the private sector. However, it may result in a
      parallel system, whereby the poor cannot access drugs if these are not available
      in the budget pharmacy. Equity is a concern in the absence of an adequate
      mechanism to protect the poor from catastrophic health expenditure.

PMID- 19754521
TI  - Reduced oviposition of Aedes aegypti gravid females in domestic containers with
      predatory fish.
AB  - The presence of pathogens or predators in water may alter oviposition behaviour
      of gravid female Aedes aegypti mosquitoes. We evaluated the oviposition behaviour
      of A. aegypti in recipients containing larvivorous fish (Betta splendens and
      Poecilia reticulata). In four breeders, fish specimens were placed in 15 l of
      dechlorined water. Four control breeders only contained dechlorined water.
      Breeders with eucatex ovitraps and approximately 100 male and female mosquitoes
      were placed in wire netting cages. During a period of 7 weeks, eggs on the
      ovitraps were counted weekly. The median number of eggs laid in recipients with
      B. splendens (32.5/week) was lower than in those with P. reticulata (200.5/week)
      and the control group (186.5/week; P < 0.0001). The oviposition activity index
      (OAI) for P. reticulata did not show any considerable difference between posture
      in deposits with and without fish (-0005). Deposits with B. splendens showed a
      lower position than those used as controls (-0627). We conclude that B. splendens
      can be used to effectively prevent gravid A. aegypti females from laying eggs in
      large water containers.

PMID- 19754522
TI  - Allogeneic blood transfusion does not increase the risk of wound infection in
      total knee arthroplasty.
AB  - BACKGROUND AND OBJECTIVE: Allogeneic blood transfusion has been reported to
      increase the risk of postoperative infection in arthroplasty though the results
      are inconclusive. Data from a previous clinical trial on antibiotic prophylaxis
      in knee arthroplasty were analysed to gain further insight into the relationship
      between wound infection and both blood transfusion and the storage time of
      transfused RBCs. MATERIALS AND METHODS: A total of 910 consecutive patients
      undergoing primary knee arthroplasty were prospectively followed for 12 months
      after surgery. The main outcome was wound infection, either superficial or deep
      tissue. Possible predictors for wound infection included the patient's age and
      sex, preoperative physical status, time under leg ischaemia, postoperative fluid
      drainage, and the number and length of storage of transfused RBCs. RESULTS: Deep
      tissue infection was diagnosed in 28 (3%) patients, superficial infection in 25
      (2.7%) and cellulitis in eight (0.8%) patients. Transfusion of at least one blood
      unit had been given to 22 (36%) of the 61 patients who later developed wound
      infection and 313 (36%) of those who did not (P > 0.05). Patients who developed
      wound infection had a significantly poorer physical status and longer time of leg
      ischaemia. There was no significant difference between both groups of patients in
      either the amount or the length of storage of transfused RBC units. CONCLUSION:
      This study failed to find any association between the incidence of wound
      infection after knee arthroplasty and allogeneic transfusion.

PMID- 19754523
TI  - Evaluation of the confidential unit exclusion form: the Canadian Blood Services
      experience.
AB  - BACKGROUND: In the mid-1980s, confidential unit exclusion (CUE) was implemented
      to permit donors unwilling to admit risk factors in screening to exclude their
      donation from transfusion. With changes in donor behaviour, epidemiology of
      disease and improvements in testing, many blood establishments have stopped using
      it. We evaluated its benefit in Canada, and reported its utility in predicting
      transmissible-disease (TD) and high-risk behaviour. STUDY DESIGN AND METHODS: TD
      positive donations and incident cases between 2004 and 2008 were analyzed in CUE
      safe and CUE-unsafe designated donations. An anonymous survey of 40,000 donors
      asked about CUE use and risk factors. RESULTS: There were 7104 (0.15%) donations
      designated CUE-unsafe of 4,775,044 donations. Most TD-positive donations were
      designated CUE-safe (1023/1030, 99.32%) with only seven (0.68%) designated CUE
      unsafe. Of 95 incident cases, all were designated CUE-safe including three NAT
      yield cases (1 HIV and 2 HCV). In the survey, some donors found the CUE difficult
      to understand [10.5% (first-time), 3.2% (repeat)], only half thought that the
      blood would still be tested [48.9% (first-time), 45.9% (repeat)], and about a
      fifth believed that collection site staff could see their designation. No survey
      respondents who used the CUE admitted to risk behaviour, but about 1% of donors
      who designated CUE-safe had high-risk behaviours. CONCLUSION: The data do not
      provide any indication of a safety benefit from CUE, but CUE use results in a
      small but constant loss of apparently safe donations.

PMID- 19754524
TI  - Problems with irradiators.

PMID- 19754525
TI  - Arbitrary social norms influence sex differences in romantic selectivity.
AB  - Men tend to be less selective than women when evaluating and pursuing potential
      romantic partners. The present experiment employed speed-dating procedures to
      test a novel explanation for this sex difference: The mere act of physically
      approaching a potential romantic partner (vs. being approached), a behavior that
      is more characteristic of men than of women, increases one's attraction to that
      partner. This hypothesis was supported in a sample of speed daters (N = 350) who
      attended a heterosexual event where either men (eight events) or women (seven
      events) rotated from one partner to the next while members of the other sex
      remained seated. Rotators were significantly less selective than were sitters,
      which meant that the tendency for men to be less selective than women at events
      where men rotated disappeared at events where women rotated. These effects were
      mediated by increased self-confidence among rotators relative to sitters.

PMID- 19754526
TI  - Sequential dynamics of culturally moderated facial expressions of emotion.
AB  - There is consensus that when emotions are aroused, the displays of those emotions
      are either universal or culture-specific. We investigated the idea that an
      individual's emotional displays in a given context can be both universal and
      culturally variable, as they change over time. We examined the emotional displays
      of Olympic athletes across time, classified their expressive styles, and tested
      the association between those styles and a number of characteristics associated
      with the countries the athletes represented. Athletes from relatively urban,
      individualistic cultures expressed their emotions more, whereas athletes from
      less urban, collectivistic cultures masked their emotions more. These culturally
      influenced expressions occurred within a few seconds after initial, immediate,
      and universal emotional displays. Thus, universal and culture-specific emotional
      displays can unfold across time in an individual in a single context.

PMID- 19754527
TI  - Social-evaluative threat and proinflammatory cytokine regulation: an experimental
      laboratory investigation.
AB  - This study experimentally tested whether a stressor characterized by social
      evaluative threat (SET), a context in which the self can be judged negatively by
      others, would elicit increases in proinflammatory cytokine activity and alter the
      regulation of this response. This hypothesis was derived in part from research on
      immunological responses to social threat in nonhuman animals. Healthy female
      participants were assigned to perform a speech and a math task in the presence or
      absence of an evaluative audience (SET or non-SET, respectively). As
      hypothesized, stimulated production of the proinflammatory cytokine tumor
      necrosis factor-alpha (TNF-alpha) increased from baseline to poststressor in the
      SET condition, but was unchanged in the non-SET condition. Further, the increases
      in TNF-alpha production correlated with participants' cognitive appraisals of
      being evaluated. Additionally, the ability of glucocorticoids to shut down the
      inflammatory response was decreased in the SET condition. These findings
      underscore the importance of social evaluation as a threat capable of eliciting
      proinflammatory cytokine activity and altering its regulation.

PMID- 19754528
TI  - Canine and Feline Reproduction VI: reproductive biology and medicine of domestic
      and exotic carnivores. Foreword.

PMID- 19754529
TI  - Endocrinologic control of normal canine ovarian function.
AB  - In dogs, the termination of the 3-10-month obligate anoestrus involves selection
      of a cohort of LH-sensitive follicles, presumably from a wave of dominant small
      antral follicles that would otherwise undergo atresia. The number and size of
      such follicles appears to increase, especially during the last 50 days of
      anoestrus when the already elevated concentrations of FSH become further
      elevated. The final selection and eventual terminal development of these
      follicles is caused by an increased frequency of high-amplitude LH pulses at the
      end of anoestrus. Concomitant increases in FSH are typically small or negligible.
      High concentrations of FSH in anoestrus are likely to be important in
      maintaining, if not stimulating, overlapping waves of dominant follicles
      throughout anoestrus, their expression of aromatase activity and basal oestradiol
      secretion sufficient to suppress LH by negative feedback. An attractive
      hypothesis is that late anoestrus increases in LH-stimulate synthesis of
      precursor androgen for already available FSH-dependent aromatase. After 7 or more
      days of elevated LH, and perhaps 2-5 days of semi-autonomous growth, with maximal
      oestradiol production reached, follicle capacity to further increase oestradiol
      becomes limited and excess progesterone becomes increasingly secreted. The pre
      ovulatory LH surge and oestrus onset are then triggered - often synchronously and
      in concert with the terminal maturation of the follicles - by central effects of
      the large decrease in the oestrogen to progestin ratio. Follicular endocrine and
      paracrine events during and following the LH surge are likely similar to those
      reported for other species. The prolonged luteal phase lengths of 55-75 days in
      non-pregnant bitches bracket the 64 +/- 1 day in pregnancy and represent a
      genetically programmed luteal cell lifespan approximating gestation length as
      occurs in the luteal phase of hysterectomized animals of most polyoestrous
      artiodactyls and rodents. The 30-40-day slow regression after day 20 to 30
      involves periodic cell death, diminution in cell size, low levels of apoptosis
      and minimal or modest involvement of endogenous prostaglandin F (PGF) production.
      The canine corpus luteum (CL) is dependent on both LH and prolactin as
      stimulating luteotrophins by day 15, and as required luteotrophins by days 20-25,
      if not earlier. Thereafter, both luteotrophins likely have cellular mechanisms of
      action similar to those reported for other species. Progesterone secretion during
      pregnancy is greatly enhanced by characteristic, and probably relaxin-stimulated,
      increases in prolactin concentration starting at or after day 25, and persisting
      to term. Near term, foetoplacental maturation results in the placental release of
      large, luteolytic amounts of PGF for 1-2 days pre-partum. Pre-partum luteolysis,
      like that induced by exogenous prostaglandin, likely involves a cascade enhanced
      by the removal of progesterone inhibition of PGF release and some degree of intra
      luteal PGF synthesis. That a likely twofold or greater increase in progesterone
      production by the CL of pregnancy does not result in significantly higher serum
      progesterone than in non-pregnant metoestrus relates to several biological
      changes, including a large increase in plasma volume of distribution, increased
      metabolism of progesterone by increased uterine, placental and mammary masses and
      increased liver clearance and excretion of progesterone and progesterone
      metabolite. Anoestrus length and ovarian cycle intervals, variable within and
      among bitches, are likely affected by neuroendocrine components of an endogenous
      circannual cycle, albeit only photo-entrained in the Basenji breed. This may be
      modified by the prior luteal phase, exposure to oestrus female pheromones and as
      yet unknown mechanisms that likely operate via inhibitory opioidergic and/or
      stimulatory dopaminergic hypothalamic pathways affecting late anoestrus increases
      in LH.

PMID- 19754530
TI  - Genomic imprinting in Canis familiaris.
AB  - For the vast majority of mammalian genes, maternally- and paternally-derived
      alleles behave identically and are either expressed or repressed, regardless of
      whether they were inherited from egg or sperm. For imprinted genes, however, this
      is not the case. The alleles of imprinted genes are epigenetically modified in a
      parent-of-origin-specific manner and, as a consequence, maternally- and
      paternally-derived alleles behave differently. Typically one allele is expressed
      while the other is silent. Although relatively few in number, imprinted genes are
      the focus of intensive study, as they have important roles in embryonic
      development. Abnormal expression of imprinted genes results in growth disorders
      and is implicated in several clinical conditions. Most studies of imprinted genes
      have been performed in rodents or primates, with limited studies in other mammals
      such as bovine and opossum. We have recently demonstrated the existence of
      imprinted genes in the canine, by showing that the canine insulin-like growth
      factor 2 receptor gene (IGF2R) is monoallelically expressed, with predominant
      expression of the maternally-derived allele and repression of the paternally
      inherited allele. Our ultimate goal is to characterize all imprinted genes in the
      canine, and to understand how they contribute to canine reproduction, development
      and disease. Such knowledge will be vital for optimizing the success of most
      reproductive strategies in the canine.

PMID- 19754532
TI  - Gonadectomy in cats and dogs: a review of risks and benefits.
AB  - The necessity, and in particular the timing, of gonadectomy in dogs and cats is
      still controversial. This is mainly because gonadectomy confers a mixture of
      benefits and adverse effects that depend upon the age at neutering, sex, species
      and breed. In this paper, the long-term risks and benefits of gonadectomy, at
      various ages, in dogs and cats are reviewed using data describing the effects of
      desexing on the urogenital tract and on other medical conditions, such as
      orthopaedic diseases, immune-mediated diseases, tumour development and behaviour.

PMID- 19754531
TI  - Development of new stem cell-based technologies for carnivore reproduction
      research.
AB  - New reproductive technologies based on stem cells offer several potential
      benefits to carnivore species. For example, development of lines of embryonic
      stem cells in cats and dogs would allow for the generation of transgenic animal
      models, which could be used to advance both veterinary and human health.
      Techniques such as spermatogonial stem cell transplantation (SSCT) and testis
      xenografting offer new approaches to propagate genetically valuable individual
      males, even if they should die before producing sperm. These techniques might
      therefore have application to the conservation of endangered species of
      carnivores, as well as to biomedical research. Recently, our laboratory has
      successfully performed SSCT in the dog, with a recipient dog producing sperm of
      donor genetic origin. Testis xenografting has been used to produce sperm from pre
      pubertal testis tissue from both cats and ferrets. These early steps reinforce
      the need not only for research on stem cell technologies, but also for additional
      research into complementary technologies of assisted reproduction in carnivores,
      so that the widest array of research and clinical benefits can be realized.

PMID- 19754533
TI  - Clinical use of deslorelin for the control of reproduction in the bitch.
AB  - This study was conducted to evaluate clinical efficacy of deslorelin for
      inhibiting reproduction in the bitch. Ten adult healthy bitches or bitches with
      mammary neoplasia for which owners were requesting suppression of cyclicity
      without performing gonadectomy were administered a 4.7- or a 9.4-mg deslorelin
      implant subcutaneously. The first implant of deslorelin was administered in
      anoestrus (n = 5) or in dioestrus (n = 5). Treatment was repeated every 5 months
      for as long as necessary based on the clinical situation of the dog and owner's
      desires. Some of the bitches implanted in anoestrus came in heat within 4-15 days
      after treatment, while none of the bitches implanted in dioestrus showed heat
      during treatment. Suppression of reproductive cyclicity was successfully achieved
      in 6/10 bitches for 1-4 years. No behavioural and local/general side-effects were
      observed in any of the treated bitches. The 4.7-mg deslorelin implant may work
      well for suppression of cyclicity provided that it is administered in dioestrus
      and at intervals of 4.5 months. A 9.4-mg implant may be more suitable for this
      use although its efficacy may also be shorter than 12 months. Owner compliance is
      an important limiting factor.

PMID- 19754534
TI  - Review and update: genomic and molecular advances in sex determination and
      differentiation in small animals.
AB  - Inherited disorders of sexual development are important to identify as a cause of
      inherited infertility or sterility in humans and animals. Investigation of these
      disorders in dogs and cats can identify new mutations, allowing us to eliminate
      inherited disorders from breeding populations, while contributing to the
      understanding of mammalian sexual development and differentiation. This review
      updates an overview of normal mammalian sexual development while discussing
      disorders of sexual development at three consecutive levels, as errors in sex
      chromosome constitution, gonadal sex determination or phenotypic sexual
      development. The molecular mechanisms controlling sexual development and current
      molecular methods to identify causative mutations are illustrated in three
      specific examples of abnormal sexual development reported in small animals: XX
      sex reversal, Persistent Mullerian Duct Syndrome and cryptorchidism.
      Identification of causative mutations and development of practical tests to
      identify carrier and affected animals will provide effective mechanisms to reduce
      the prevalence of these disorders in small animals.

PMID- 19754535
TI  - Advances in reproductive science for wild carnivore conservation.
AB  - Knowledge about reproduction is critical for predicting the viability of wildlife
      populations in nature and for managing breeding programmes in captivity.
      Intensive species-based studies are the priority, because reproductive mechanisms
      are extraordinarily diverse, even within the same taxonomic family. Carnivores
      deserve more attention as such species are highly vulnerable to environmental
      change and human persecution. The present review provides contemporary
      illustrations of how reproductive science is contributing to understand unique
      reproductive mechanisms that are both of fundamental and applied interest. In the
      case of the endangered African wild dog (Lycaon pictus) free-living in South
      Africa, non-invasive faecal corticosteroid assessments have yielded new insights
      about the impact of animal relocation and reintroduction on adaptive responses,
      reproductive fitness and survival. For the maned wolf (Chrysocyon brachyurus),
      advances have been made in characterizing and comparing reproductive traits in
      free-ranging vs captive individuals. For the cheetah (Acinonyx jubatus), recent
      studies have focused on the cryosensitivity of sperm and the ability to develop a
      field-friendly sperm cryo-method. The by-product has been a large-scale frozen
      repository of sperm from wild-caught cheetahs useful for infusing new genes into
      ex situ populations. Finally, rigorous, multi-disciplinary and cross
      institutional reproductive studies of the black-footed ferret (Mustela nigripes),
      including the use of artificial insemination, have contributed to the remarkable
      recovery and restoration of this species, once on the brink of extinction. In
      summary, advances in reproductive science are not necessarily related to
      'assisted breeding'. However, understanding the unique ways of carnivore
      reproduction greatly contributes to species management and conservation.

PMID- 19754536
TI  - Follicular dynamics, ovulation and conception rates in bitches.
AB  - Real-time ultrasound imaging was used in a clinical study to estimate the number
      of follicles of different sizes, ovulation and conception rates, and to study
      follicle dynamics following oestrus-induction of bitches. Follicles were
      identified during late anoestrus (between 100 and 60 days prior to the pre
      ovulatory LH surge) and there appeared to be a shift in the population from small
      follicles (1-3 mm in diameter) to large follicles (>4 mm diameter) approximately
      2 days prior to the LH surge. Corpora lutea could be reliably identified although
      the majority were cavitated. High ovulation rates (97-100%) and pregnant rates
      (86-100%) were detected, and although the conception rate was approximately 70%
      it varied between 8 and 92%. Within the narrow range of the clinical population
      studied there were trends relating age to reproduction performance. Oestrus
      induction with a gonadotrophin regime appeared to result in large numbers of
      small follicles that did not ovulate, whilst when using cabergoline the number of
      small and large follicels and the number of copora lutea were similar to those of
      control cycles.

PMID- 19754537
TI  - Comparison of selected endocrine parameters during luteal phase and pregnancy in
      German Shepherd dogs and Beagles.
AB  - Concentrations of progesterone, prolactin and relaxin in serum at predetermined
      intervals after ovulation (day 0) in non-pregnant and pregnant normocyclic
      Beagles were assayed and results compared with those observed in German Shepherd
      dogs (GSD) in a previous study. The goal was to determine possible reproductive
      hormone specificities related to the GSD breed. Furthermore, the effects of
      medroxyprogesterone acetate (MPA)-treatment in non-pregnant Beagles and of
      progesterone supplementation in pregnant Beagles on the hormone concentrations
      were examined. Mean concentrations of progesterone and prolactin were not
      different in the non-pregnant Beagles compared with those seen in non-pregnant
      GSD, except at days 50-60, when progesterone concentrations were found to be
      higher in Beagles (p < 0.05). Mean progesterone concentrations in pregnant
      Beagles at days 50-60 after ovulation (day 0) were higher (p < 0.05) than in GSD
      at that time, but not at earlier time periods. Prolactin concentrations were
      higher (p < 0.05) in Beagles throughout pregnancy compared with those in the GSD.
      Mean relaxin concentrations were numerically but not significantly lower in GSD
      than in Beagles throughout pregnancy. A 10-day oral MPA treatment did not affect
      progesterone or prolactin secretion in normocyclic non-pregnant Beagles.
      Medroxyprogesterone acetate serum concentrations were approximately 3.9 ng/ml
      during treatment and decreased to 0.42 and 0.021 ng/ml within 5 and 15 days after
      end of treatment, respectively. Intramuscular progesterone supplementation from
      days 30 to 40 in pregnant Beagles resulted in higher concentrations of
      progesterone in the 36- to 45-day time periods; prolactin and relaxin
      concentrations were not significantly affected during or after treatment compared
      with administration of placebo. The results suggest a tendency towards deficient
      luteal function in the short-cycle GSD bitches previously studied, which in
      pregnancy may reflect the observed decreased prolactin concentrations; the
      possibility that GSD relaxin secretion is deficiency required needs further
      study. As oral treatment with MPA did not affect progesterone and prolactin
      release, it may be useful for studying luteal function in pregnant bitches with
      suspected hypoluteoidism.

PMID- 19754538
TI  - Follicular morphology, oocyte diameter and localisation of fibroblast growth
      factors in the domestic dog ovary.
AB  - Remarkably little is known about folliculogenesis in the dog. Objectives were to
      characterise (1) changes in follicle/oocyte diameter and granulosa cell number
      and (2) localisation of fibroblast growth factor (FGF)-2 and FGF-7 during dog
      ovarian follicle development. Fourteen ovarian pairs were excised and processed
      for histological evaluation. Two to four serial sections/bitch were stained with
      hematoxylin, and follicle/oocyte diameters and granulosa cell number were
      determined at each developmental stage. Mean follicle and oocyte size were
      compared among stages by one-way analysis of variance. Relationships between
      follicle and oocyte size and granulosa cell number were determined using
      correlation and regression analysis, respectively. Another eight serial
      sections/bitch were processed for immunostaining to determine FGF-2 and FGF-7
      localisation. Primordial and primary follicles were similar in size, but smaller
      than the progressively increasing (p < 0.05) diameter of the later stages. Oocyte
      diameter gradually increased (p < 0.05) among oocytes derived from primordial,
      primary, secondary and early antral follicles with no difference (p > 0.05)
      thereafter. Oocyte size and granulosa cell number increased (p < 0.01) with
      follicular diameter. Except during anoestrus, FGF-2 occurred in oocytes and
      granulosa cells of primordial to secondary follicles. In adult bitches, FGF-7 was
      localised in granulosa cells of primary and secondary follicles and also occurred
      in the theca layer of antral follicles during prooestrus and oestrus. In summary,
      folliculogenesis in the domestic dog occurs in two phases: pre-antral phase
      characterised by increasing follicle size in association with oocyte growth and
      granulosa cell proliferation and antral phase linked with marked granulosa cell
      proliferation and accumulation of antral cavity fluid. Finally, the temporal
      localisation pattern of FGF-2 implies its role in follicular activation, whereas
      FGF-7 activities appear related to later folliculogenesis.

PMID- 19754539
TI  - Expression pattern of markers in the canine ovarian cycle.
AB  - Although hormonal changes during different phases of the oestrous cycle of
      bitches are well-described, knowledge about the luteal phase and anoestrus is
      incomplete. Furthermore, which paracrine and autocrine critical factors that
      differentiate between follicles destined for atresia and those that continue to
      develop are unknown. In this study, ovarian tissue was collected from 39 healthy
      bitches that were subject to ovariectomy or ovariohysterectomy for surgical
      neutering or medical purposes such as unwanted pregnancy. Bitches were allocated
      to different groups depending on the stage of the oestrous cycle. Serum
      progesterone, LH, FSH and 17beta-estradiol (E(2)) -levels were determined and
      immunhistochemistry was performed for a variety of receptor antigens; Ki-67,
      vimentin, pan cytokeratin antibody, p53 and oestrogen receptor (ER) alpha
      antigens. Marked differences were found in progesterone concentration between
      pregnant and non-pregnant animals. Oestrogen concentration was significantly
      lower in pro-oestrus and ovulation than during the luteal phase. Although
      progesterone could be detected in cytoplasm of ovarian cells at each stage, its
      presence was restricted to follicular cells during anoestrus. A strong presence
      of AE1/AE3, vimentin and p53 was found in each oestrous stage, in contrast with
      Ki67. The localization of ERalpha appeared to vary during the oestrous cycle, a
      phenomenon that suggests a switch between target cells of oestrogen; while as a
      proliferation marker, the mild reaction of p53 during parturition suggests an
      apoptotic process at this stage of the cycle.

PMID- 19754540
TI  - Plasma LH, ovulation and conception rates in cats mated once or three times on
      different days of oestrus.
AB  - Although cats are induced ovulators, the relationship between the day of
      breeding, the number of matings and the likelihood of ovulation and conception
      have not been extensively investigated. In this experiment, cats were mated
      either once or three times on day 1 or day 5 of oestrus to study the incidence of
      the LH surge, ovulation and conception rates. The percentage ovulating and the
      conception rates after a single mating on day 1 of oestrus were 60% (6/10) and
      33.3% (2/6), respectively, and for cats mated once on day 5 of oestrus were 83.3%
      (10/12) and 40% (4/10), respectively. When cats were mated three times on day 1
      of oestrus, the ovulation rates and conception rates were 70% (7/10) and 85.7%
      (6/7), respectively, and for those mated three times on day 5 of oestrus were
      100% (10/10) and 100% (10/10), respectively. The concentration of LH did not
      increase in non-ovulating cats, and cats that were mated three times had LH
      concentrations that were numerically higher than those that were mated once.
      Litter size was neither related to the day of mating nor to the number of
      matings. Although an increase in the number of matings on day 1 of oestrus
      produced a numerically larger LH surge, it did not increase the ovulation rate,
      suggesting that plasma oestradiol concentrations were not sufficiently elevated
      to induce a high pituitary response to mating stimulation. The conception rate
      after a single mating was low, suggesting that the number of sperm per mating was
      not sufficient. These results suggest that mating more than once in the middle of
      oestrus is required to improve ovulation rates and conception rates in cats.

PMID- 19754541
TI  - Controlled delivery of a GnRH agonist by a silastic implant (Gonazon) results in
      long-term contraception in queens.
AB  - Many female cats are spayed to prevent problems associated with calling and
      unwanted pregnancies. This study describes the safety and efficacy of an
      alternative approach, using an azagly-nafarelin containing implant (Gonazon)
      inserted subcutaneously in the neck of six treated queens for 3 years. These six
      queens together with six controls were permanently housed with vasectomized tom
      cats, and changes in progesterone concentrations were used to document the
      contraceptive efficacy of Gonazon. All six control queens ovulated regularly
      throughout the treatment period (3 years), as shown by regular changes in
      progesterone concentration. Sixteen ovulatory cycles were observed in each
      control throughout the study. In Gonazon treated queens, during the week
      following implant placement, two queens displayed a treatment-induced rise in
      progesterone concentration. Later on, all treated queens continuously displayed
      low progesterone concentrations until 3 years post-implant insertion, with the
      exception of a single isolated episode (at approximately 2.5 years of treatment),
      of follicular luteinization in two queens. In all queens, azagly-nafarelin
      concentrations peaked in the week following implant insertion remained high for 1
      month and later decreased slowly. After 2.5 years of treatment, azagly-nafarelin
      concentrations were still greater than 150 pg/ml in 3/6 queens. During a 6-month
      long extension of the study (36-42 months post-treatment), all queens (treated
      and controls) were run with intact tom cats. None of them conceived. Following
      autopsy, ovarian weight and diameter of the uterine horns of 3/6 treated queens
      were shown to be similar to those of the controls. In conclusion, this study
      demonstrated that Gonazon efficiently prevented ovulation in queens (100%) for 3
      years. Return to fertile heat was not observed towards the end of treatment.
      However, in half of the treated queens, reversibility of the treatment induced
      effects on the genital tract was demonstrated.

PMID- 19754542
TI  - Comparison between vestibular and subcutaneous insertion of deslorelin implants
      for oestrus induction in bitches.
AB  - Investigations using sustained-release deslorelin implants at various insertion
      sites have shown that this method consistently induces oestrus in anoestus
      bitches. However, fertility comparisons between implant insertion sites have not
      been performed. Anestrous beagle bitches received one 2.1 mg deslorelin implant
      beneath the vestibular mucosa (VM group; n = 6) or in the subcutaneous tissue
      between the shoulder blades (SubQ group; n = 8). Vestibular implants were removed
      when serum progesterone concentrations first exceeded 1.5 ng/ml. Vaginal
      cytologies and blood samples were collected daily and bitches were inseminated
      during oestrus. Serum progesterone and deslorelin concentrations were measured
      and pregnancy status was determined using ultrasonography. There were no
      differences between groups in the intervals between implant administration and
      the onset of proestrus, the time of the luteinizing hormone surge and the onset
      of cytologic diestrus. There were also no differences in the number of corpora
      lutea or foetuses. However, conception rate was significantly lower in the SubQ
      group. The pregnancy rate did not differ significantly between the VM and SubQ
      groups [4 out of 6 (66.7%) and 3 out of 8 (37.5%), respectively]. One bitch
      (16.7%) in the VM group and three bitches (37.5%) in the SubQ group suffered
      distinct, premature declines in serum progesterone concentrations starting 1-4
      weeks after cytologic diestrus. Serum progesterone concentrations did not recover
      (premature luteal failure), resulting in abortion. Bitches with premature luteal
      failure in the SubQ group still had serum deslorelin concentrations >100 pg/ml 20
      days after implant insertion, suggesting a possible association between prolonged
      deslorelin release and luteal failure.

PMID- 19754543
TI  - Non cat-like ovarian cycle in the Eurasian and the Iberian lynx -
      ultrasonographical and endocrinological analysis.
AB  - The Iberian lynx is considered the most endangered felid species. Therefore, an
      ex situ conservation program was initiated to protect this species from
      extinction. Additional knowledge on lynx reproduction biology and reliable
      methods for reproductive monitoring are important for developing a captive
      breeding program. The aim of this study in lynx was to implement transrectal
      ultrasonography to visualize ovarian structures (follicles, corpora lutea) and to
      assess ovarian activity in addition to analysis of serum progesterone and
      oestradiol. Because of limited access to Iberian lynxes, the less-endangered
      Eurasian lynx and bobcat were also studied in this comparative study. Recent
      endocrinological studies based on faecal and urinary progesterone and oestrogen
      metabolites revealed that steroid profiles in both these species were alike and
      did not follow the typical pattern of other felids. Pregnancy diagnosis was not
      possible, since progesterone concentrations did not differ between pregnant and
      pseudopregnant animals. Progesterone was also detected after parturition as well
      as after weaning until the onset of a new oestrous cycle. In the present study,
      the presence of corpora lutea during the non-breeding season was confirmed by
      ultrasonography and by elevated serum levels of progesterone averaging 3.56 +/-
      1.3 ng/ml in Eurasian and 6.1 +/- 0.26 ng/ml in Iberian lynx, respectively. The
      ultrasonographical findings on the ovarian structures suggest strongly that
      corpora lutea developed after ovulation stay active until November and regress
      before the onset of the next oestrus.

PMID- 19754544
TI  - Seasonal profiles of ovarian activity in Iberian lynx (Lynx pardinus) based on
      urinary hormone metabolite analyses.
AB  - The Iberian Lynx Ex-Situ Conservation Programme is an essential part of a co
      ordinated action plan to conserve the most endangered felid species of the world.
      Successful captive breeding demands reliable methods for reproduction monitoring
      including reliable non-invasive pregnancy diagnosis. During a 3-year study, urine
      samples from six captive Iberian lynx females were obtained (one non-pregnant,
      one pseudo-pregnant and 11 pregnant cycles). Progesterone, pregnanediol and
      oestradiol were determined in urinary extracts and relevant urinary oestrogen
      metabolites were characterized by high-performance liquid chromatography (HPLC).
      Urinary progestins did not follow the typical pregnancy-related course of felids.
      In the lynx, we failed to demonstrate an urinary progestin elevation during
      pregnancy. In contrast, urinary oestrogens increased from 3.8 +/- 0.6 to 8.6 +/-
      0.5 ng/mg creatinine (p < 0.001) during the pregnancy. A comparison of pseudo
      pregnant with pregnant cycles revealed a further increase of oestrogens caused by
      implantation (p < 0.05). In one female, which refused to mate, no difference was
      estimated between oestrogens levels during the breeding and non-breeding seasons.
      Almost 10-fold higher oestrogen concentrations were measured in urines of females
      that shared enclosures with males. HPLC analysis of oestrogens in urine samples
      collected from Iberian lynx during the pregnancy revealed that lynx urine is
      composed of two polar oestrogen metabolites in addition to oestrone and minor
      amounts of oestradiol. Oestrone was detectable in all urinary extracts (8-12% of
      metabolites), whereas oestradiol was elevated only during late pregnancy (18%).
      Thus, seasonal luteal activity in Iberian lynx can be monitored by urinary
      oestrogens. The increase of urinary oestradiol during late pregnancy might
      indicate an oestradiol secretion by the lynx placenta.

PMID- 19754545
TI  - Gonadal activity in male and female captive fossas (Cryptoprocta ferox) during
      the mating season.
AB  - The fossa is an endangered, mongoose-like carnivore species endemic to Madagascar
      with a breeding season (BS) in the southern hemisphere spring. For the present
      study, faecal samples of captive fossas were collected for over 1 year for five
      males and four non-pregnant females, and for two pregnant animals during the
      reproductive period. The goal was to assess gonadal activity using non-invasive
      hormone measurements of faecal testosterone (T) and gestagen metabolites using
      assays previously established in our laboratory and further validated in this
      study. All study animals were housed in northern hemisphere zoos. In males, the
      seasonal T metabolite profile revealed a peak in spring (March). High performance
      liquid chromatography (HPLC) analysis was used to characterize the faecal hormone
      metabolite composition. The highest immunoreactivity was detected in the position
      of dihydrotestosterone, whereas native T was not detected. In the two pregnant
      females, gestagen metabolite concentrations increased 4-9 days after the initial
      matings and remained elevated throughout gestation with concentrations
      dramatically higher than those of the non-pregnant females during the BS. In
      these females, gestagen metabolite analyses did not reveal a seasonal pattern
      similar to the males. The HPLC-analysis revealed that the major proportion of
      immunoreactivity was associated with an unknown metabolite, whereas native
      progesterone was undetectable. The seasonal hormone pattern of male fossas gives
      proof of the reproductive seasonality of this species. The elevated 5alpha
      pregnan-3beta-ol-20-one levels in pregnant animals allows for the
      characterization of pregnancy in the fossa based on analysis of faecal steroid
      metabolite concentrations.

PMID- 19754546
TI  - Expression of MHC-I and -II in uterine tissue from early pregnant bitches.
AB  - The aim of the study was to investigate the expression of major
      histocompatibility complex (MHC)-I and -II in uterine tissues from pregnant and
      non-pregnant bitches, taken at different time periods after mating. The pregnant
      bitches were ovariohysterectomized during the pre-implantation (group 1, n = 4),
      implantation (group 2, n = 7) and placentation stage (group 3, n = 7). Non
      pregnant animals in diestrus served as controls (group 4, n = 7). The expression
      of MHC- I and -II in salpinx, apex, middle horn, corpus uteri and at implantation
      sites was investigated by immunohistochemistry as well as qualitative and
      quantitative RT-PCR; MHC-I mRNA was detected in all tissues and with quantitative
      RT-PCR, and no significant changes were detected until placentation.
      Immunohistologically, at the apex and corpus site, the average number of MHC-II
      positive cells increased from the pre-implantation to the post-implantation stage
      (apex: 1.54 +/- 1.21 to 3.82 +/- 2.93; corpus: 1.62 +/- 1.9 to 5.04 +/- 4.95; p <
      0.05). The greatest numbers of MHC-II positive cells were observed at
      placentation sites (6.64 +/- 5.9). In parallel, a marked increase in the relative
      mRNA expression of MHC-II in uterine tissues was assessed from the pre
      implantation to the placentation stage (relative to Glycerinaldehyd-3-phosphate
      Dehydrogenase (GAPDH): 6.9 +/- 9.5, 8.4 +/- 5.8, p > 0.05). Immunohistologically,
      in the salpinx, significantly greater numbers of MHC-II positive cells were found
      in the tissues of pregnant animals than in the control group (p < 0.05). It is
      proposed that the increase in MHC-II is pregnancy-related, even though the impact
      on maintenance of canine pregnancy is still unclear.

PMID- 19754547
TI  - Uterine progesterone receptor and leukaemia inhibitory factor mRNA expression in
      canine pregnancy.
AB  - The study investigated the expression of genes for progesterone receptor (PR) and
      for the cytokine leukaemia inhibitory factor (LIF) in the uterine tube and
      uterine horn tissues from pregnant and non-pregnant bitches. The aim was to study
      whether a relation existed between the likely biological effectiveness of
      progesterone (P(4)) and the change in the uterine expression of LIF mRNA during
      pregnancy, as has been described in primates. For this purpose, 20 pregnant
      bitches were ovariohysterectomized after being allotted to three groups according
      to gestational age (pre-implantation: days 10 to 12, n = 7; peri-implantation:
      days 18 to 25, n = 7; post-placentation: days 28 to 45, n = 7). Tissue samples
      were obtained from the uterine tubes, one uterine horn (including placentation
      sites and interplacental sites in bitches that had already implanted) and the
      corpus uteri, stored at -80 degrees C, and then analysed by qualitative and
      quantitative PCR for PR and LIF mRNA expression. From the pre-implantation to the
      placentation stage, a decrease in the relative expression of PR mRNA in uterine
      tissue was obvious and significant when expressed relative to beta-actin (11.2 +/
      6.8 vs 2.7 +/- 1.9; p < 0.05). However, over the same period, the relative
      expression of LIF mRNA increased (10.1 +/- 16.1 vs 50.0 +/- 32.3; p < 0.05). In
      addition, PR mRNA went from being detectable to no longer detectable in the
      uterine tube, and no longer detectable in interplacental-site uterine tissue. We
      conclude that LIF is important for the establishment of canine pregnancy; that
      decreased uterine PR mRNA expression may contribute to the increase in uterine
      LIF mRNA; and, that the ability of the embryo to preserve PR mRNA expression at
      implantation and placentation sites while expression is lost in the remainder of
      the uterus represent an effect important to the establishment and maintenance of
      pregnancy. We additionally propose that canine embryo secretory proteins have a
      regulatory effect on both PR and LIF before as well as at and after implantation.

PMID- 19754548
TI  - Cytokines, growth factors and prostaglandin synthesis in the uterus of pregnant
      and non-pregnant bitches: the features of placental sites.
AB  - Uterine tissue from pregnant bitches was investigated by qualitative RT-PCR for
      the gene expression of local factors potentially important for the implantation
      of canine embryos. For this purpose, 10 bitches identified as being at the time
      of implantation or early placentation by means of ultrasonography before
      ovariohysterectomy (days 20-35, n = 10) provided tissues for comparison to tissue
      collected in a previous study and identified as early pregnant (n = 10) or non
      pregnant (n = 4) by embryo flushing after ovariohysterectomy (days 10-12 after
      mating; Schafer-Somi et al. 2008). Uterine tissue was excised from the middle of
      the left horn from early pregnant and non-pregnant animals, including from
      interplacental and placentation sites. The following genes were investigated: CD
      4, -8; cyclooxygenase (COX)-1, -2; granulocyte macrophage-colony stimulating
      factor (GM-CSF); hepatocyte growth factor (HGF); insulin-like growth factor (IGF)
      1, -2; transforming growth factor (TGF) and tumour necrosis factor (TNF)-alpha;
      interferon (IFN)-gamma; interleukin (IL)-1beta, -2, -4, -6, -8, -10, -12;
      leukaemia inhibitory factor (LIF) and leptin. Gene expression for CD-8, COX-1,
      TGF-beta, HGF, IGF-1, IL-2, -4,-10, IFN-gamma and LIF were detected in the pre
      implantation uterus, and all except IL-2 and -10 were still detectable during the
      implantation and placentation stage. During implantation, mRNA for IGF-2 and GM
      CSF were additionally detected. The dioestrous uterus differed from the pregnant
      uterus because of the absence of CD-8, IL-4 and IFN-gamma and the expression of
      CD-4, TNF-alpha and IL-6. The results suggest that IL-4, IFN-gamma, CD-8, GM-CSF
      and IGF-2 are regulated in a pregnancy-specific manner and that GM-CSF and IGF-2
      probably have growth supporting and immune modulating functions during
      implantation of the canine embryo.

PMID- 19754549
TI  - The role of the ovary for the maintenance of pregnancy in cats.
AB  - Plasma progesterone (P(4)) concentrations are maintained in pregnant cats until
      parturition, but become low in pseudopregnant cats 40-45 days after infertile
      mating. This difference in P(4) concentrations is considered to be due to P(4)
      secretion by the placenta of pregnant cats. Therefore, to clarify these points,
      we performed ovariectomy (OVX) at various stages of pregnancy, examined the
      pregnancy status and measured LH and P(4) concentrations in peripheral, ovarian
      and uterine venous blood. After OVX, abortion occurred in 100% (5/5), 80% (4/5),
      40% (2/5) and 60% (3/5) of Groups I (Day 35), II (Day 40), III (Day 45) and IV
      (Day 50) cats, respectively. In the remaining cats, normal delivery took place on
      days 63-69 [mean, 66.1 +/- 1.1 (SE)] of pregnancy. The time to abortion after OVX
      was 4-8 (mean, 5.6 +/- 0.8), 3-17 (mean, 8.0 +/- 3.6), 10 and 11, and 2-4 (mean,
      3.0 +/- 0.7) days in Groups I, II, III and IV, respectively. The plasma P(4)
      concentrations were 1-2 ng/ml in all groups on the day after OVX, decreasing to
      less than 1 ng/ml from the 2nd day onwards. The concentrations of P(4) in ovarian
      venous blood at the time of OVX decreased with the stage of pregnancy, but were
      clearly higher than those in peripheral blood. The plasma P(4) concentrations in
      uterine venous blood were similar to those in peripheral blood. These results
      suggest that peripheral P(4) in pregnant cats is the result of P(4) secretion
      secreted only by the ovarian corpus luteum, not by the placenta, but indicate
      that either P(4) is not essential for the maintenance of pregnancy in cats from
      day 40-45 of pregnancy onwards, or that the placenta provides a local source of
      P(4) that does not appear in measurable amounts in the peripheral circulation.

PMID- 19754550
TI  - Pregnancy monitoring in dogs and cats using 3D and 4D ultrasonography.
AB  - Three-dimensional (3D)/four-dimensional (4D) volume ultrasound is an established
      method in human medicine that offers various options for analysing and presenting
      ultrasound volume data. However, the successful application of the different
      3D/4D imaging modalities in pregnant dogs and cats has not yet been reported in
      the literature. The main reasons for this are: (1) the high costs of 3D/4D
      ultrasound systems, (2) operation difficulties due to high breathing frequency in
      non-sedated animals and (3) the missing specific knowledge in veterinary medicine
      concerning how to perform high-quality volume scans. Automatically acquired
      ultrasound volume data sets were generated with two different ultrasound systems:
      the portable Voluson i and the stationary Voluson Expert 730. Different 3D/4D
      imaging modalities were tested in regard of their practicability in pregnancy
      monitoring in dogs and cats. Nine different volume imaging modalities were
      applied using the saved files. For the presentation of the static 3D volume data
      sets, we used the multiplanar, niche, surface, transparency, glass body,
      inversion, volume calculation and tomographic ultrasound imaging modes. For the
      dynamic 4D data, the surface and glass body modes were applied. By changing the
      human standard settings to the requirements of small animal anatomy, it was found
      that 3D/4D ultrasound has great potential for the characterization of pregnancy
      in queens and bitches. The 3D/4D technology offered advanced information about
      pregnancy status and birth prediction and improved the diagnostic confidence. By
      using standardized examination protocols, 3D/4D ultrasound will allow a reduction
      in examination time by generating even more relevant information. These benefits,
      combined with possible future cost reduction of commercial ultrasound systems,
      might lead to frequent utilization in routine pregnancy diagnostic and birth
      management in small animal practice.

PMID- 19754551
TI  - Progesterone, oestradiol, FSH and LH concentrations in serum of progesterone
      treated pregnant bitches with suspected luteal insufficiency.
AB  - In the bitch, the corpus luteum is the only source of circulating progesterone
      throughout pregnancy. Inadequate luteal function may be a cause of abortion or
      foetal resorption observed after early pregnancy diagnosis. In our study of
      factors involved in canine luteal inadequacy, 35 pregnant bitches from different
      breeds were allocated to groups of healthy control (n = 15) vs hypoluteoid (n =
      20) pregnant bitches, based on presence or absence of clinical signs of impending
      abortion and on progesterone concentrations below 10 ng/ml at the 4th-5th week of
      pregnancy. Hypoluteoid bitches were treated daily with 10-mg natural progesterone
      in injectable form (Luteosan inj.; Alvetra and Werfft AG, Vienna, Austria) until
      day 60. Serum progesterone, 17beta-oestradiol, FSH and LH concentrations were
      measured in samples obtained weekly using ELISA previously validated for dog
      serum. The exogenous progesterone supplementation was presumed to be sufficient
      to prevent foetal loss in 15 of the 20 treated bitches. The mean serum
      progesterone concentration in control pregnant bitches did not decrease below 10
      ng/ml until the 8th week of pregnancy. Progesterone concentrations in
      progesterone-treated hypoluteoid bitches at week 4 were lower than in controls (p
      < 0.05), but although numerically higher did not differ significantly from those
      of controls during the period of treatment. Serum 17beta-oestradiol
      concentrations of healthy bitches were variable, were at most time higher than
      those of treated animals and slowly decreased until parturition; those of treated
      bitches remained unchanged during the study. Serum FSH and LH concentrations did
      not differ between groups. Additional studies involving untreated pregnancies
      showing equivalent evidence of hypoluteoidism as well as assay of circulating
      relaxin and prolactin in treated and untreated bitches are needed to better
      determine the causes and effects of hypoluteoidism in pregnant bitches.

PMID- 19754552
TI  - Peripartum haemodynamic status of bitches with normal birth or dystocia.
AB  - There has been limited investigation of parturition in the bitch and there is
      little information published on clinical and obstetrical examination other than
      opinion and anecdote. While there are substantial data on haemodynamic and
      vascular changes during normal parturition in humans, little is known about the
      physiological events in the dog. This study was aimed at maternal haemodynamic
      changes occurring during normal parturition and to investigate how these were
      modified in bitches with dystocia (DYST) treated either medically or via assisted
      delivery and caesarean operation. Three groups of 10 bitches were investigated;
      those with normal parturition, those with DYST corrected by manipulative
      assistance or caesarean operation and those with uterine inertia treated by
      oxytocin administration. Heart rate, systolic and diastolic blood pressure,
      electrocardiogram and blood glucose concentration were measured pre-partum, intra
      partum, immediately after parturition and 1 h later. Heart rate was high at all
      times throughout the study and the majority of bitches had normal sinus rhythm.
      Blood pressure was generally within the normal range, and although systolic and
      diastolic blood pressure was highest during the intra-partum period and sometimes
      during the immediate post-partum period, there were no significant differences
      between groups. All bitches had blood glucose concentrations within the normal
      range throughout the study although pre-partum concentrations were statistically
      lower than many of the other time periods. The study provides useful
      physiological data that will facilitate monitoring and clinical management of
      bitches throughout normal parturition and DYST.

PMID- 19754553
TI  - Pulmonary maturation in canine foetuses from early pregnancy to parturition.
AB  - Development of the foetal respiratory system includes both pulmonary growth and
      maturation. In human medicine, a higher incidence of respiratory distress is
      reported in newborn males. This study aimed to identify different phases of
      canine foetal lung maturation throughout pregnancy, to determine the stage of
      pregnancy in which surfactant production begins and to compare pulmonary
      development of male and female foetuses. Pregnant bitches (34) were subjected to
      elective ovariohysterectomy and allocated into four groups, according to the
      stage of pregnancy: 30-40 days of pregnancy (n = 10), 41-50 days (n = 10), 51-60
      days (n = 10) and bitches in the first stage of parturition (n = 4). Foetal lungs
      were histologically processed and evaluated by optical microscopy. The
      pseudoglandular phase was identified between the 35th day and 46th day of
      gestation; the onset of canalicular and saccular periods was observed,
      respectively, from the 48th day and 60th day of pregnancy. Lungs from foetuses at
      term were in the saccular phase; thus, the development into the alveolar period
      occurs in the neonatal period. The histological analyses revealed that
      respiratory tract development is centrifugal, from upper to lower airways.
      Therefore, it is possible to identify distinct development periods in different
      portions of the same organ. In conclusion, the saccular phase of lung development
      begins around 57 and 60 days of pregnancy, the period in which surfactant
      production is believed to occur. Male and female foetuses present similar
      pulmonary development from early pregnancy until parturition.

PMID- 19754554
TI  - Dystocia in numbers - evidence-based parameters for intervention in the dog:
      causes for dystocia and treatment recommendations.
AB  - Dystocia is a frequent problem in the dog, with regard to breed-specific factors,
      litter size, duration of expulsion, various intervals between puppies and various
      causes of maternal, foetal or combined origin. In the present study, results were
      obtained from management of 530 dogs of 54 breeds, between 1 and 13 years of age,
      presented with dystocia over a period of 8 years in an obstetrical clinic with
      mostly identical diagnostic and therapeutic schedules. Data on age of the dam,
      parturition number, breed size, causes of dystocia, duration of expulsion time,
      kind of obstetrical aid, and last but not least, the influence of all therapeutic
      aspects on survival of the puppies were analysed. Dams of miniature and small
      breeds (59.4%) had a high incidence for dystocia in this population. Uterine
      forces (inertia and spasm), malpresentation of the foetus and litter size (single
      pup pregnancies, hyperfoetation) were the most common causes for dystocia.
      Duration of expulsion stage had the highest influence on puppy survival (p <
      0.001). In the case of medical treatment, medication with oxytocin led to higher
      puppy losses compared with other medicaments. Older primiparous bitches (>6 years
      of age) had a significantly higher risk to have special obstetric conditions and
      stillbirths compared with young primiparous bitches. The scope of this study was
      to analyse the parameters that were most useful for a rapid diagnosis to maximize
      puppy survival, to avoid false diagnosis and to choose the best therapeutic
      strategy. The present data show that in addition to the established criteria for
      management of dystocia in the dog, new diagnostic approaches are necessary to
      improve obstetrical care.

PMID- 19754555
TI  - Effect of an injectable cabergoline formulation on serum prolactin (PRL) and milk
      secretion in early postpartum Beagle bitches.
AB  - This study was conducted in order to evaluate effects on prolactin (PRL)
      concentration and mammary milk secretion of an injectable cabergoline formulation
      administered to five lactating Beagle bitches during early postpartum (PP).
      Bitches were bled twice daily (from PP day 3 to PP day 12) and then daily (from
      PP day 13 to PP day 16) to assay serum PRL. On PP day 6, a subcutaneous (SC)
      injection of 0.1 ml/kg of placebo was administered. On PP day 9, a SC 0.1 ml/kg
      dose of injectable cabergoline was administered. All bitches were checked for
      milk production, using a clinical scoring in order to quantify milk expression
      from each teat. A circadian variation of serum PRL was evident during the 6 days
      of pre-treatment monitoring. The day after cabergoline injection, an 80% decrease
      of PRL serum concentration was observed (p < 0.05). The circadian oscillatory
      pattern of PRL secretion disappeared after administration of cabergoline, and PRL
      values remained significantly lower than in the previous days for the first 60 h
      following treatment (p < 0.001). Milk production was drastically reduced when
      comparing pre-treatment to post-treatment scores (p < 0.001). A single dose of
      injectable cabergoline caused a significant reduction in serum PRL concentration
      and a significant reduction in milk flow. The injectable formulation of
      cabergoline appeared to be safe and well tolerated.

PMID- 19754556
TI  - Post-partum involution of the canine uterus - gross anatomical and histological
      features.
AB  - We aimed to study the normal puerperium in the bitch. Ovariohysterectomy was
      performed in nine bitches, each at a different day after normal whelping; their
      genital tract was subject to gross anatomical examination, as well as to
      histological examination and electron microscopy scanning. Corpora albicans were
      evenly distributed in the left and right ovaries and placental sites were evenly
      distributed among left and right uterine horns. Placental sites were initially of
      dark green to grey colour, later becoming dark brown; their length and height
      progressively decreased. Height of the myometrium and diameter of the uterine
      glands progressively decreased. Trophoblast-like cells were consistently observed
      at the placental sites and on the surface of the interplacental areas, at all
      time points where hysterectomy had been performed. It is suggested that
      involution of the canine genital tract can last up to 3 months and is slow.
      Continuous (up to D84 post-partum) presence of prominent placental sites should
      be considered a normal feature of canine uterine post-partum involution.

PMID- 19754557
TI  - Comparison of two doses of the GnRH antagonist, acyline, for pregnancy
      termination in bitches.
AB  - Gonadotropin-releasing hormone (GnRH) antagonists are particularly useful when a
      rapid inhibitory effect on the gonadal axis is required. The aim of this study
      was to test the efficacy and clinical safety of a low and high dose of the third
      generation GnRH antagonist, acyline, on pregnancy termination in female dogs. The
      effect of the antagonist on the progesterone (P(4)) serum concentration was also
      described. Twenty-one mid-pregnant bitches were randomly assigned to a single
      subcutaneous (SC) dose of a placebo (PLACE; n = 7), a low (ACY-L; 110 microg/kg;
      n = 6) or high (ACY-H; 330 microg/kg; n = 8) dose of acyline. The animals were
      followed up for 15 days. All ACY treated but no placebo-treated animals
      terminated their pregnancy by abortion (p < 0.01). The ACY-L and ACY-H groups
      interrupted their pregnancy 7 +/- 1.9 and 6.4 +/- 1.3 days after treatment,
      respectively (p = 0.7). A significant interaction between treatment and day was
      found (p < 0.01) for P(4) serum concentrations when PLACE was compared with both
      ACY groups. No difference was found for this hormone between both ACY groups (p >
      0.05) where P(4) diminished throughout the study. The decreasing rate varied
      among animals and was closely related to the time of abortion when P(4) reached
      basal concentrations. In PLACE animals, gestation progressed normally and P(4)
      did not change throughout the study (p > 0.05). None of the bitches presented
      side effects. It was concluded that acyline safely terminated mid-pregnancy by
      permanently decreasing P(4) serum concentrations.

PMID- 19754558
TI  - Neonatal clinical evaluation, blood gas and radiographic assessment after normal
      birth, vaginal dystocia or caesarean section in dogs.
AB  - This study aimed to standardize signs and diagnostic criteria of respiratory
      function in newborn puppies delivered normally or after dystocia and caesarean
      operation. A total of 48 neonates were allocated into groups: eutocia (n = 20),
      dystocia (n = 8), caesarean (c)-section (n = 20). Neonatal health was assessed
      using the Apgar score and body temperature was determined at 0, 5 and 60 min
      after delivery. Venous blood gases (pO(2) and SO(2)) was measured immediately and
      60 min after delivery, and a thoracic radiograph was made between 0 and 5 min of
      life. The c-section group had significantly lower Apgar scores at birth and 5
      min. Hypothermia was present at 5 min in the eutocia and c-section groups, and at
      60 min in all groups. The eutocia group had an irregular respiratory pattern in
      78% of puppies at birth, 27.7% at 5 min and 21% at 60 min compared with 87.5%,
      62.5% and 12.5% of the pups in the dystocia group where there was irregular
      respiratory rhythm, moderate to intense respiratory sounds with agonic episodes.
      The c-section group had respiratory alterations in 70%, 45% and 16% of puppies at
      0, 5 and 60 min, respectively. Radiographic abnormalities were present in 17% of
      the pups in the eutocia group, 25% of the pups in the dystocia group and 30% of
      the pups in the c-section group, respectively. The c-section group had
      significantly lower SO(2) values at 60 min than at birth. All puppies had
      hypoxaemia, but a significant decrease was observed in the c-section group.
      Newborn puppies had tissue hypoxia and irregular respiratory pattern at birth.
      Caesarean-section puppies had lower vitality; however, all developed satisfactory
      Apgar scores at 5 min of life, regardless of the obstetric condition.

PMID- 19754559
TI  - An experimental model to study resistance index and systolic/diastolic ratio of
      uterine arteries in adverse canine pregnancy outcome.
AB  - The aim of this study was to describe the changes in the resistance index (RI)
      and systolic/diastolic ratio (S/D) of the uterine arteries during mid-pregnancy
      abortion induction in the dog. Sixteen 30-35 day pregnant bitches were randomly
      assigned to either a pharmacological protocol to interrupt gestation (n = 8) or
      were used as untreated control group (n = 8). Doppler assessments of uterine
      arteries blood flow were carried out before the initiation of the protocol and
      then every other day up to abortion (treated group) or parturition (control
      group). All treated bitches aborted 6 +/- 1.2 days after initiation of the
      treatment (while none of the non-treated bitches aborted). Pre-treatment RI and
      S/D did not differ between groups (p > 0.2) while average post-treatment indexes
      were (mean +/- SD): 0.62 +/- 0.1 vs 0.53 +/- 0.1 (p < 0.01) and 2.96 +/- 0.9 vs
      2.23 +/- 0.3 (p = 0.01), for the treated and non-treated group respectively.
      Correlations between days to abortion and RI or S/D were 0.75 (p < 0.01) and 0.79
      (p < 0.01) and, -0.78 (p < 0.01) and -0.73 (p < 0.01) for the treated and non
      treated groups respectively. In the treated group, correlations between serum
      progesterone (P(4)) concentrations and RI and S/D were -0.76 (p < 0.01) and -0.59
      (p < 0.01) respectively. It is concluded that, during induction of abortion, RI
      and S/D of uterine arteries progressively increased while P(4) decreased.

PMID- 19754560
TI  - Clinical evaluation of the use of aglepristone associated with oxytocin to induce
      parturition in bitch.
AB  - To evaluate the efficacy and safety of aglepristone 15 mg kg(-1) for induction of
      parturition in bitches, 22 pregnant beagle bitches were injected subcutaneously
      on day 60 post-estimated LH surge, and again 24 h later with aglepristone and
      subsequently were given 0.15 IU kg(-1) oxytocin at hourly intervals until
      delivery of the last puppy. Six pregnant beagle bitches were used as a non
      treated control group. In the control group, parturition occurred at 63.2 +/- 0.5
      days, 29 pups were born and the average expulsion time per puppy was 1.0 +/- 0.6
      h. In the treated group, parturition was obtained on average 29.7 +/- 5.6 h after
      aglepristone administration, 121 pups were born and average expulsion time per
      pup was 1.1 +/- 0.4 h. The percentage of live puppies, 7 weeks after birth, was
      86.1% (25/29) and 86.8% (105/121) for the control and treated groups,
      respectively. No significant difference was observed between the control and
      treated groups for the average expulsion time per live puppy and for the
      percentage of live puppies at birth, 48 h, 7 days or 7 weeks after birth (p >
      0.05). This study confirms previous results and demonstrates that the combination
      of aglepristone and oxytocin can be safely and reliably used to induce
      parturition in beagle bitches, at 60 days post-estimated LH surge.

PMID- 19754561
TI  - Induction of parturition with aglepristone in various sized bitches of different
      breeds.
AB  - The objective of this study was to confirm in various breeds of dogs the efficacy
      and safety of a parturition induction treatment described to be successful in
      Beagle dogs. Parturition was induced in seven various sized pregnant bitches of
      different breeds, with 15 mg aglepristone per kg at day 59-61 post-estimated
      ovulation day, followed 24 h later by 0.15 IU oxytocin per kg subcutaneous
      injections every 2 h. Two bitches were small-sized bitches (<10 kg), three
      bitches were large-sized bitches (30-40 kg) and two bitches were giant bitches
      (>40 kg). The results were compared to a control group (n = 6), in which bitches
      underwent a natural delivery in the same environmental conditions as the induced
      group. In the induced group, parturition was successfully induced in 7/7 bitches.
      The first pup in a litter was born on average 25.9 +/- 3.29 h after aglepristone
      administration (21-30 h). Two of seven bitches from the small-sized group
      delivered some of their pups before the first administration of oxytocin. The
      mean duration of parturition was 9.6 +/- 5.4 h vs 8.0 +/- 4.8 h in the control
      group. The mean interval between two successive pups being delivered was 115.6 +/
      82.8 min (34-265) vs 68.8 +/- 24.5 min in the control group (p < 0.03). The mean
      weight at parturition did not differ significantly between the two groups. One
      litter of four Yorkshire Terrier pups in the induced group were premature at the
      time of birth and died between 19 and 29 h post-delivery. This study, although on
      a very limited number of dogs, confirms the efficacy of the aglepristone/oxytocin
      protocol to induce parturition in dogs.

PMID- 19754562
TI  - Influence of progesterone withdrawal on pregnancy-related parameters during post
      implantation early pregnancy loss.
AB  - Pharmacologically-induced luteolysis or treatment with an antiprogestin in early
      post-implantation pregnancy in dogs results in asynchronous death and resorption
      of conceptuses, indicating variable rates of response of individual conceptuses
      towards progesterone deficiency. This variability also seems to occur in bitches
      showing pregnancy failure in response to spontaneous luteal deficiency. In a
      total of 10 beagle pregnancies (two consecutive pregnancies of five bitches),
      abortifacient treatments beginning on day 24 after ovulation (ov) involved either
      administration of a progestin antagonist (total of six pregnancies, in three
      bitches) or a luteolytic regimen of prostaglandin F(2alpha)-analogue together
      with a dopamine agonist (total of four pregnancies, in two bitches). The outcomes
      were evaluated in relation to four control pregnancies in two bitches by assay of
      serum progesterone, prolactin and relaxin at selected time points or within
      selected time periods, by ultrasound of conceptuses including measurement of
      uterine blood flow, and parameters of the blood fibrinolytic system including
      plasma fibrinogen and plasminogen. The process of embryonic death and conceptus
      resorption was variable in onset and duration both in bitches that received the
      progesterone antagonist aglepristone (AGLE) and in those under the luteolytic
      treatment (cloprostenol combined with cabergoline). Pregnancy termination (death
      of all embryos or foetuses, respectively) occurred as early as day 29 and as late
      as day 41 after ov in AGLE-treated bitches, and not earlier than day 37 after ov
      in luteolytic-treatment bitches. Impending embryonic death was not predicted by
      changes in relaxin concentration, parameters of the fibrinolytic system, or in
      the perfusion of small uteroplacental vessels.

PMID- 19754563
TI  - Elective caesarean operation in the bitch using aglepristone before the pre
      partum decline in peripheral progesterone concentration.
AB  - The aim of this study was to investigate caesarean operation (CO) undertaken
      before the pre-partum decrease of progesterone but following administration of a
      progesterone receptor antagonist and to evaluate the innocuity of this procedure
      for the dam and pups. Thirty seven bitches of 15 different breeds, received an
      injection of 15 mg/kg aglepristone 59 or 60 days after the estimated day of
      ovulation, determined by progesterone quantitative assays, and caesarean section
      (CS) was performed between 20 and 24 h after administration. Progesterone
      remained above 6 nmol/l at the time of CS (mean = 15.75, SD = 3.84). No post
      operative clinical complications were reported in any of the bitches. All bitches
      were able to nurse and feed their puppies in the first 24 h following surgery. No
      pups showed any signs of prematurity and 5 out of 188 pups (2.6) died in the
      first 2 weeks after delivery. This small study demonstrates that a CS may be
      safely and successfully performed an average of 2 days before the expected date
      of parturition following the administration of aglepristone, without any harmful
      consequence for the dam and her neonates.

PMID- 19754564
TI  - Morphological examination of the corpora lutea from pregnant bitches treated with
      different abortifacient regimes.
AB  - Different abortifacient regimes in dogs were analysed for their effect on the
      pregnancy corpora lutea (CL), namely, prostaglandin F2a analogue cloprostenol
      (CLO) combined with dopamine agonist cabergoline (CAB), or progesterone (P4)
      receptor antagonist aglepristone (AGL). Ovaries were collected after 6-10 days of
      treatment during first trimester. The CL of the control-group showed strong
      expression of relaxin (RLX), its receptor RXFP1 and enzymes of steroid
      biosynthesis (HSD) with high peripheral P4-levels. Whereas RXL, RXFP1 and HSD
      were lowest expressed in the CLO/CAB-group with a massive degeneration of CL and
      their blood vessels combined with low peripheral P4-level. The AGL-group showed
      less extensive CL degeneration and more intensive staining of the examined
      factors than CLO/CAB. In summary, all examined factors are associated with normal
      luteal function and are useful tools to stage luteolysis. Although both
      treatments have the same abortive action, their sequence of events on the CL is
      different.

PMID- 19754565
TI  - Urinary incontinence in spayed bitches: new insights into the pathophysiology and
      options for medical treatment.

PMID- 19754566
TI  - Lactoferrin in canine sera: a pyometra study.
AB  - The concentration of lactoferrin was measured in canine sera from groups of
      healthy male dogs as well as pregnant and non-pregnant female dogs and was
      compared with that of bitches with pyometra. Lactoferrin concentrations were
      higher in bitches with pyometra. The role of elevated lactoferrin concentrations
      in the suppression of lymphocyte activity was examined in sera from bitches with
      pyometra in a series of investigations. Although the sera from bitches with
      pyometra were capable of suppressing lymphocyte activity, lactoferrin was not
      found to be involved in this action.

PMID- 19754567
TI  - Diagnosis of endometritis in the bitch: a new approach.
AB  - There are a few investigations into endometritis in the bitch and its
      relationship with failure to conceive remains unclear. This may be because of the
      difficulty in collecting uterine samples for further investigations. Recently,
      transcervical catheterization by vaginal endoscopy has been introduced allowing
      the evaluation of the endometrium. In this study, uterine cytology and
      bacteriology were evaluated in 26 infertile bitches. Endometritis was bacterial
      in origin in most cases (70% of affected bitches), but these results may be
      underestimated, as some other pathogens (anaerobic bacteria, mycoplasms and
      fungi) were not investigated. Endometritis, in our opinion, should be
      investigated in each case of unexplained infertility in bitches. The method used
      here seems reliable although defining more accurate classification criteria will
      improve the efficiency of this non-invasive technique.

PMID- 19754568
TI  - Prostaglandin synthesis genes are differentially transcripted in normal and
      pyometra endometria of bitches.
AB  - Pro-inflammatory stimuli, such as endotoxins released by Gram-negative bacteria,
      are potent stimulators of prostaglandin (PG) synthesis. The aim of this study was
      to evaluate the gene transcription pattern of PG synthesis enzymes in normal
      (anestrous, n = 6 and diestrous, n = 8) and pyometra (n = 7) endometria of
      bitches. Uteri were collected during routine ovariohysterectomy, processed for
      histopathological evaluation and uterine contents cultured. Gene transcription of
      COX-1, COX-2, mPGES-1 and PGF-synthase (PGFS) were evaluated by relative real
      time PCR and normalized with the ribosomal protein L27 (RPL27) housekeeping gene.
      Normal uteri had no histological abnormalities and were negative for
      bacteriology. All pyometra uteri were hyperplasic and Escherichia coli was the
      only isolated bacterium. Except for COX-1, gene transcription was significantly
      higher in pyometra than in normal endometria. No significant differences in gene
      transcription were observed between normal diestrous and anestrous endometria.
      COX-2 gene transcription was 19 and 69 times higher in pyometra than in diestrous
      and anestrous endometria (p < 0.001), while PGFS gene transcription had a 3- and
      600-fold increase in pyometra endometria compared to normal diestrous and
      anestrous endometria (p < 0.001). Gene transcription of mPGES-1 was 9 times
      higher in pyometra than in normal uteri (p < 0.01). Based on these results, we
      suggest that pyometra-associated E. coli endotoxin release stimulates the up
      regulation of COX-2 PGFS and mPGES-1 gene transcription in the endometrium.

PMID- 19754569
TI  - Effects of the anti-progestin aglepristone on the uterine tissue of cats
      administered medroxyprogesterone acetate.
AB  - The effect of aglepristone, a progesterone receptor antagonist, on feline
      endometrial proliferation induced by medroxyprogesterone acetate (MPA), a
      contraceptive progestin, was investigated. Three groups each of six cats were
      studied: Group A, during inter-oestrus; Group B, given 50 mg MPA; Group C,
      receiving 50 mg MPA followed by 10 mg/kg aglepristone twice at 24-h interval 3
      weeks later. Ovariohysterectomy was performed, and uterine tissue was collected
      from the mid part of the horn when the cats were confirmed as being in inter
      oestrus (Group A), 3 weeks after the MPA administration (Group B), or 2 weeks
      after aglepristone administration (Group C). Uterine weights, relative uterine
      weights and uterine diameters were determined. The endometrial and myometrial
      thicknesses and the endometrial/myometrial ratios were determined in histological
      sections. Histological sections were also immunostained for proliferative
      activity [anti-proliferative cell nuclear antigen (PCNA) antibody], and
      progesterone receptor (anti-hPR) and percentage of positive cells in luminal vs
      glandular epithelium were determined for both parameters. PCNA and all
      morphological parameters except endometrial thickness were increased (p < 0.05)
      by MPA, and progesterone receptor was decreased compared to untreated cats.
      Aglepristone treatment had no significant effect compared to MPA alone. However,
      glandular proliferative activity was usually but not significantly lower in Group
      C than in Group B, suggesting a potential effect of the anti-progestin that might
      be clinically beneficial. Alternatively, this possible effect in the aglepristone
      group may reflect the longer time after MPA that these animals were examined.
      Whether lack of significant effect of the anti-progestin was because of too high
      dose of MPA relative to the dose of aglepristone, the delay of 14 days in
      obtaining tissues after aglepristone treatment, or simply an insufficient
      duration of aglepristone treatment requires further study.

PMID- 19754570
TI  - Acid-base changes in canine neonates following normal birth or dystocia.
AB  - There are limited data concerning blood gas parameters in neonatal dogs.
      Knowledge of the normal physiology may facilitate effective therapeutic
      intervention and potentially reduce neonatal mortality. This study examined acid
      base parameters in pups born at normal parturition (n = 27) compared with those
      born after obstetrical assistance or caesarean operation (n = 13) and those born
      following oxytocin (OXY) administration for treatment of uterine inertia (n =
      11). Pups were subjected to an objective scoring method of neonatal health
      adapted from use in humans (the Apgar score) at birth and again at 5 and 60 min
      after birth. Venous blood samples were collected at 5 and 60 min after birth for
      evaluation of blood gas parameters. At birth, all pups had low Apgar scores and a
      mixed acidosis. The base excess was lowest for pups delivered after OXY
      administration. The Apgar score improved for all pups after 5 min of birth and
      there was an improvement in carbon dioxide tension, base excess and venous blood
      pH at 1 h, although in all pups a metabolic acidosis persisted. These data
      provide an important insight into neonatal physiology and the variability of
      blood gas parameters in pups born at normal and abnormal parturition and provide
      the basis for clinical decision making following dystocia.

PMID- 19754571
TI  - Thyroid function and infertility in the dog: a survey in five breeds.
AB  - In our study, a clinical and reproductive examination was undertaken in 204 dogs
      of five different breeds. Thyroxine and thyroid-stimulating hormone plasma
      concentrations were assayed in order to assess the real incidence of
      hypothyroidism associated with reproductive disease. Among these animals, only
      two breeds were affected by hypothyroidism (4.5% of the Dogue de Bordeaux and
      2.4% of the Leonbergers). Moreover, these animals did not suffer from any
      reproductive disease. Our study showed also that 70% of the male Dogue de
      Bordeaux were hypothyroxinemic compared with Great Danes, English Mastiff and
      Leonbergers whose male population was 100% normothyroidic. We found the same
      tendency in bitches. In our data, there was no difference in thyroxin plasma
      concentrations between normo- and hypofertile dogs, but our results were not
      statistically significant.

PMID- 19754572
TI  - Isolation of canine mammary cells with stem cell properties and tumour-initiating
      potential.
AB  - Recent data suggest that mammary carcinogenesis may be driven by cancer stem
      cells (CSCs) derived from mutated adult stem cells, which have acquired aberrant
      cell self-renewal or by progenitor cells that have acquired the capacity for cell
      self-renewal. Spontaneous mammary cancers in cats and dogs are important models
      for the understanding of human breast cancer and may represent alternative
      species model systems that can significantly contribute to the study of human
      oncogenesis. With the goal of identifying markers for isolating human breast
      CSCs, we have generated a canine model system to isolate and characterize normal
      and CSCs from dog mammary gland. Insight into the hierarchical organization of
      canine tumours may contribute to the development of universal concepts in
      oncogenesis by CSCs. Cells with stem cell properties were isolated from normal
      and tumoural canine breast tissue and propagated as mammospheres and
      tumourspheres in long-term non-adherent culture conditions. We showed that cells
      obtained from spheres that display self-renewing properties, have multi-lineage
      differentiation potential, could generate complex branched tubular structures in
      vitro and form tumours in NOD/SCID mice. We analysed these cells for the
      expression of human stem and CSC markers and are currently investigating the
      tumour-initiating properties of these cells and the hierarchical organization of
      normal and neoplastic canine mammary tissue.

PMID- 19754573
TI  - Expression of ABC-transport proteins in canine mammary cancer: consequences for
      chemotherapy.
AB  - Intrinsic or acquired drug resistance is a major barrier for chemotherapy of
      cancer. Importantly, the presence of ATP-binding cassette, ABC-transport proteins
      in tumour cells circumvents an intracellular accumulation of chemotherapeutic
      drugs. In this study, 103 canine mammary tumour probes were investigated for mRNA
      expression of seven ABC-transporters by RT-PCR. All tumour samples expressed
      multidrug resistance-associated protein 1 (MRP1) and breast cancer resistance
      protein (BCRP). MRP7 was detected in 97.1% of tumour probes, MRP3 in 96.1%, Pgp
      in 92.2%, MRP5 in 85.4% and MRP6 in 64.1%. More of the half of tumour samples
      (56.1%) expressed all of the examined ABC-transport proteins. Approximately one
      third of the tumour samples (32.7%) were lacking in one transporter and only
      11.2% possessed from three to five transporters. The canine transporter cBCRP was
      functionally analysed in stable transfected Madin-Darby canine kidney-II cells
      using an MTT viability test. cBCRP transfected cells showed a 5.4-fold resistance
      to 10 microm doxorubicin. Cell survival in the presence of methotrexate was not
      affected by cBCRP. In conclusion, absence of efficiency of chemotherapy of canine
      mammary cancer can be caused by expression of seven various ABC-transport
      proteins. Because cBCRP is expressed in all examined tumour probes and induces
      resistance to doxorubicin, the application of doxorubicin for treatment of canine
      mammary is inappropriate.

PMID- 19754574
TI  - Investigation of the local expression of the relaxin system in canine mammary
      tumours.
AB  - While mammary tumours are the main reasons of death in bitches, early detection
      of tumours and metastases is crucial for survival of affected dogs. Invasiveness
      and angiogenesis, which are important processes of tumour growth and spreading,
      require connective tissue remodelling. This process is dominantly mediated by
      matrix metalloproteinases (MMP), which are well known to be positively regulated
      by relaxin (RLX) in various tissues, including human breast cancer. So far, the
      presence of RLX and its receptor RXFP-1 as well as their linkage with MMP in
      canine mammary tumours (CMT) is completely unknown. In the first part of the
      present study, concentrations of RLX, oestradiol and progesterone from plasma
      samples of bitches with CMT were compared with clinical and survival data to
      investigate the predictive value of these hormones. In the second part, the
      expressions of RLX, RXFP-1 and MMP-2, -9 and -13 were examined by real-time
      reverse transcriptase polymerase chain reaction (RT-PCR) in 31 CMT samples.
      Finally, relationships of systemic plasma RLX or locally expressed RLX with
      expression of MMP in CMT were analyzed for the first time. Comparison of hormone
      concentrations in 93 bitches in terms of benign or malignant nature of the CMT,
      lung metastases, recidivation and 12-month survival discovered no significances.
      The expressions of RLX, RXFP-1 and MMP were independent from plasma RLX, but
      expressions of local RLX and RXFP-1 showed a strong correlation (p = 0.00004, r =
      0.671) as well as RXFP-1 and MMP-2 (p = 0.009, r = 0.463), indicating a possible
      significant role of the locally produced RLX in CMT pathogenesis as an inducer of
      connective tissue remodelling.

PMID- 19754575
TI  - Prolonged duration of fertility of dog ova.
AB  - The fertile period for natural mating in dogs extends from before ovulation until
      day 5 post ovulation (PO) and involves a delay in oocyte maturation until 2-3
      days PO and viability of secondary oocytes for 48-60 h or more. Spermatozoa do
      not enter the uterus after vaginal insemination in late oestrus. Cervical closure
      appears to occur on average 5 days PO, but conception may occur following
      intrauterine artificial insemination (IUAI) up to 8 days PO. Therefore, the
      present study was conducted to clarify the duration of fertility of canine ova.
      Using IUAI at 6, 7, 8 and 9 days PO (n = 5 bitches each) conception rates were
      100%, 71.4%, 37.5% and 0%, respectively, with an average litter resorption rate
      of 30.8%, and with mean litter sizes and times to delivery PO being 4.3 +/- 1.6
      and 64.3 +/- 0.3 days, 4.0 +/- 1.4 and 66.3 +/- 0.4 days, and 2.5 and 68 days for
      IUAI at 6, 7 and 8 days, respectively. The high pregnancy rates with IUAI at 6
      and 7 days PO confirm that many canine oocytes are fertile at 4-5 days after
      maturation. The high rate of resorption was presumably because of aging of ova or
      asynchrony between embryonic development and the intrauterine environment.

PMID- 19754576
TI  - Functional role of feline zona pellucida protein 4 trefoil domain: a sperm
      receptor or structural component of the domestic cat zona pellucida?
AB  - The trefoil domain (TFD) is a protein structure characterized by six cysteines,
      which form a typical three-loop structure by three disulphide bridges. It is
      assumed that two of these loops generate a hydrophobic groove, which could be a
      binding site for carbohydrate residues or proteins. The zona pellucida (ZP)
      protein, ZP4, contains such a TFD. The carbohydrate-/protein-binding property of
      TFD allows us to assume a potential sperm receptor function of this domain.
      Additionally, gastrointestinal trefoil peptides are stable against proteases;
      therefore, a structural role of TFD within the ZP might also be possible. We were
      able to show that the synthesized and natural folded feline TFD (fTFD) expresses
      the typical protease resistance that vanished under reducing conditions and after
      substitution of cysteine residues within the peptide. Furthermore, an antibody
      directed against the first loop of fTFD was almost unable to bind to intact in
      vitro mature cat oocytes. Pre-incubation of oocytes in the reducing agent (DDT),
      however, improved antibody binding substantially. Therefore, we suggest
      structural masking of the fTFD domain within the intact ZP. An interaction
      between fTFD and feline sperm cells was examined using several methods, including
      immunocytochemistry, immunoelectron microscopy, co-immunoprecipitation and far
      western blot, but we found no indication for an involvement of TFD in the primary
      sperm binding to the ZP. To summarize, there is increasing evidence that the TFD
      of fZP4 has a structural rather than a sperm-binding function.

PMID- 19754577
TI  - Oestrogen and progesterone receptor gene expression in canine oocytes and cumulus
      cells throughout the oestrous cycle.
AB  - The aim of this research was to analyze oestrogen receptor-alpha (ERalpha),
      ERbeta and progesterone receptor (PR) gene expression in the canine oocyte and
      cumulus cells throughout the oestrous cycle. Ovaries from 38 bitches were
      recovered after ovariohysterectomy and sliced. The phase of the oestrous cycle
      was determined by vaginal cytology, vaginoscopy and serum hormonal measurements.
      Oocytes were mechanically denuded by repeated pipetting. For each phase of the
      cycle, a sample was composed by a pool of 50 oocytes (sample number: prooestrus =
      3, oestrus = 8, dioestrus = 5 and anoestrus = 5) or a pool of cumulus cells
      (prooestrus = 4, oestrus = 7, dioestrus = 4 and anoestrus = 6). Oocyte and
      cumulus cells' total RNA was isolated and reverse transcription was conducted to
      perform real-time PCR. Oestrogen receptor-alpha was expressed throughout the
      cycle in the oocyte (33.33%, 25.0%, 20.0% and 60.0% for prooestrus, oestrus,
      dioestrus and anoestrus, respectively) and cumulus cells (50.0%, 47.14%, 25.0%
      and 66.67% for prooestrus, oestrus, dioestrus and anoestrus, respectively). In
      the oocyte, the ERbeta was also expressed in all phases of the cycle (33.33%,
      50.0%, 20.0% and 60.0% for prooestrus, oestrus, dioestrus and anoestrus,
      respectively), whereas in cumulus cells, ERbeta was only expressed during
      prooestrus (50%) and oestrus (14.29%). Interestingly, while the oocyte PR was not
      detected in any phase of the cycle, this receptor was expressed during prooestrus
      (50%), oestrus (42.86%) and anoestrus (16.67%) in cumulus cells. In conclusion,
      canine oocytes express ERalpha and ERbeta throughout the oestrous cycle, however,
      there is a lack of PR expression in all these phases. Moreover, in cumulus cells,
      only ERalpha was expressed throughout the oestrous cycle.

PMID- 19754578
TI  - Nuclear and cytoplasmic maturation of canine oocytes related to in vitro
      denudation.
AB  - In vitro maturation (IVM) of bitch oocytes is, to date, a very inefficient
      process, with common metaphase rates approximately 0-20% and mean degeneration
      rates approximately 20-30%. In other mammals, meiotic resumption is controlled in
      the cumulus-oocyte complex by the disappearance of the coupling between granulosa
      cells and the oocyte. The first aim of this study was to evaluate the influence
      on meiotic resumption of a mechanical denudation of the oocytes before
      maturation. The nuclear stage was determined by DNA staining with ethidium
      homodimer-2 under confocal microscopy. Denuded (n = 318) and control (n = 378; no
      mechanical denudation) oocytes had similar degeneration rates (respectively 32.1
      vs 28.6%). However, meiosis resumption rates were significantly higher for
      denuded oocytes (DO; 26.9 vs 17.8%). Secondly, we aimed to evaluate oocytes
      experiencing spontaneous denudation during the 72 h IVM period. Denuded oocytes,
      having lost cumulus cells on at least 75% of their perimeter (n = 440), were
      compared with surrounded oocytes (SO), with 100% of their perimeter surrounded by
      granulosa cells (n = 860). As above, the nuclear stage was determined by confocal
      microscopy, but cytoplasmic maturation was also evaluated through transmission
      electron microscopy. Degeneration rates but also meiosis resumption and metaphase
      rates were significantly higher for denuded than for SO (9.6 vs 2.8% for
      metaphase rate). Nevertheless, ultrastructurally, metaphase DO have scarcer
      organelles unevenly distributed, with smooth endoplasmic reticulum concentrated
      in aggregates in the cortical zone. Denudation, whether mechanical or
      spontaneous, is thus an inefficient mean to obtain metaphase II oocytes suitable
      for in vitro fertilization.

PMID- 19754579
TI  - Ultrastructural study of the canine zona pellucida surface during in vitro
      maturation.
AB  - The aim of the present study was to compare the ultrastructure of the surface of
      the zona pellucida (ZP) of immature and in vitro matured dog oocytes using
      scanning electron microscopy (SEM). Bitch oocytes were collected after
      ovariohysterectomy; the ovaries were sliced and the released cumulus-oocyte
      complexes (COCs) were washed with phosphate buffered saline (PBS). The selected
      COCs were randomly allocated into three groups, two groups were processed after
      in vitro maturation at both 72 and 96 h and a third group was processed
      immediately at immature state in PBS medium. After that, oocytes were fixed,
      critical point dried and viewed by using SEM. The diameters of the outer holes of
      the ZP were measured on a total of 93 oocytes; the results were analyzed with
      anova. The mean diameters of holes were different between groups (p < 0.05): 0.69
      +/- 0.12, 1.56 +/- 0.19 and 1.42 +/- 0.27 mum, for immature and in vitro matured
      oocytes for 72 and 96 h, respectively. The difference in the hole sizes between
      immature and in vitro matured canine oocytes indicates that the ZP surface is
      related to oocyte maturity in canines.

PMID- 19754580
TI  - Ultrastructural characteristics of non-matured and in vitro matured oocytes
      collected from pre-pubertal and adult domestic cat ovaries.
AB  - The present study describes the ultrastructural characteristics of cat oocytes
      before maturation and after 12- and 24-h in vitro maturation (IVM). Oocytes were
      recovered from pre-pubertal and adult queen ovaries after ovariohysterectomy and
      a proportion were stored in glutaraldehyde at 4 degrees C until examination by
      transmission electronic microscopy (TEM). Those selected for maturation were
      cultured before TEM in DMEM for 12 and 24 h at 38 degrees C in a humidified
      environment of 5% O(2), 5% CO(2) and 90% N(2). Specimens were divided into six
      groups: non-matured oocytes from pre-pubertal queens (PP0), non-matured oocytes
      from adult queens (A0), 12-h in vitro matured oocytes from pre-pubertal queens
      (PP12), 12-h in vitro matured oocytes from adult queens (A12), 24-h in vitro
      matured oocytes from pre-pubertal queens (PP24) and 24-h in vitro matured oocytes
      from adult queens (A24). Across the treatment groups, it was possible to observe
      differences in the thickness of the perivitelline space, the penetration of
      cumulus cell projections forming a junctional complex, distribution and density
      of small vesicles, lipid droplets, microvilli, mitochondria and cortical granules
      and variable degrees of development of Golgi complexes. These findings
      demonstrated that ultrastructural analysis of oocytes matured in vitro is a
      valuable tool to evaluate oocyte cytoplasmic maturation and that this IVM
      protocol was efficient in inducing gradual morphological changes necessary for
      cytoplasmic maturation of pre-pubertal and adult cat oocytes.

PMID- 19754581
TI  - Preliminary study in immature canine oocytes stained with brilliant cresyl blue
      and obtained from bitches with low and high progesterone serum profiles.
AB  - This study was conducted: (i) to observe the features and levels of blue colour
      impregnation in morphologically selected immature canine cumulus oocyte complexes
      (COCs) stained with the brilliant cresyl blue (BCB) dye, as indicators of
      quality, and integrity of nuclear oocyte chromatin configuration before in vitro
      maturation (IVM); (ii) to observe the relationship between the influence of serum
      progesterone (SP) concentrations from ovary donors and BCB staining of immature
      dog oocytes. The results showed that out of 138 canine COCs, germinal vesicle
      (GV) stage prevailed in BCB+ oocytes at percentages of 67.4% (60/89), which were
      statistically higher than those observed in BCB+/- (52.2%; 23/44) and BCB- (20%;
      1/5) oocytes (p = 0.023). Oocytes BCB+ were interpreted as those having completed
      their growth and therefore possessing the capacity to mature and develop in
      vitro. Ooplasm and cumulus cells (CCs) of canine oocytes were BCB staining
      independent. Ooplasm blue colour staining reaction varied between grown oocytes,
      revealing different levels of glucose-6-phosphate dehydrogenase activity among
      and within oocytes. Additionally, SP profile of ovary donors was not a relevant
      indicator for selection of oocytes screened with the BCB stain. Similar numbers
      of high quality oocytes were observed to be BCB+, BCB+/- and BCB- between groups
      of females with SP varying from 0 to 2.5 ng/ml (n = 5), and those with SP varying
      from 2.6 to 16.7 ng/ml (n = 4) (p = 0.680). It may be inferred that bitches with
      low and high SP profiles have grown oocytes in their ovaries, as determined by
      the BCB absorbance in their ooplasms.

PMID- 19754582
TI  - The influence of oxygen tension on cumulus cell viability of canine COCs matured
      in high-glucose medium.
AB  - High in vitro oxygen (O(2)) tensions are associated with enhanced levels of
      reactive oxygen species and cumulus oocyte complex (COC) apoptosis. The objective
      of this study was to determine the influence of O(2) tension on cumulus cell (CC)
      viability from canine oocytes. Cumulus oocyte complexes were distributed into
      three groups (CG, T20 and T5) and two O(2) tension levels (20% and 5%). The
      control group (CG) was matured in vitro in a humidified atmosphere with 5% CO(2)
      in air in TCM199 with 26.19 mM sodium bicarbonate, 10% (v/v) foetal calf serum
      (FCS), 0.10 mM gentamicin, 0.20 mM pyruvic acid, 20 microg/ml oestradiol, 0.5
      microg/ml follicle-stimulating hormone, 0.03 IU/ml human chorionic gonadotropin,
      and 1.0 microg/ml human somatotropin. Groups T20 and T5 were matured under 20% or
      5% O(2) tensions respectively in a high-glucose medium, without FCS. T20 and T5
      were as CG, and supplemented with 0.1% Polyvinyl Alcohol, and 5.5 mM glucose.
      After 48 h of IVM, CCs from COCs were stained with propidium iodide (1.50 mM).
      The results showed that viability of CCs (cytoplasmic features and nuclear
      morphological integrity) was different for the three groups. Rates of apoptosis
      were at 57.9% (521/900) for CG, 54.4% (490/900) for T20 and 38.9% (350/900) for
      T5 (p < 0.001). Predominant features in apoptotic cells (n = 1361) were DNA
      nuclear fragments (94.0%). It was concluded that CCs of canine COCs cultured in
      high-glucose medium showed significantly less apoptosis than those cultured in
      medium with FCS. Low O(2) tension was efficient in reducing apoptosis in canine
      CCs.

PMID- 19754583
TI  - Expression of the mu opioid receptor and effects of the opioid antagonist
      naloxone on in vitro maturation of oocytes recovered from anoestrous bitches.
AB  - The mu-opioid receptor (MOR) is expressed in bovine, human, equine and canine
      oocytes, and in seasonal breeders, it is expressed with higher intensity during
      the anoestrous phase. Supplementation of in vitro maturation (IVM) medium with
      opioid agents, agonists or antagonists, was shown to affect oocyte maturation in
      several species such as rat, bovine and equine. This study reports the effects of
      supplementing IVM medium with naloxone (Nx), an opioid antagonist, on nuclear and
      cytoplasmic maturation rate of oocytes recovered from anoestrous bitches.
      Cytoplasmic maturation was examined in terms of mitochondrial (mt) distribution.
      In order to confirm the receptor-mediated action of Nx, in oocytes of anoestrous
      bitches, MOR expression was analyzed by Western blot. Cumulus-oocyte complexes,
      recovered from the ovaries of bitches in anoestrous, were cultured in vitro and
      Nx was added at the concentrations of 1 x 10(-6), 1 x 10(-8) and 1 x 10(-10) M.
      The rate of oocytes resuming meiosis after culture in presence of 1 x 10(-6) M Nx
      (29%) was significantly higher than that of oocytes of control group (12%; p <
      0.05). However, treatment with Nx did not affect mt distribution pattern. In
      denuded oocytes and in corresponding cumulus cells, a doublet of 65 and 50 kDa
      was observed. We conclude that, in oocytes of anoestrous bitches, MOR is
      expressed and Nx significantly improves nuclear maturation rate. Further studies
      should be performed to elucidate the expression of other opioid receptors, such
      as delta and kappa, and possible interactive effects of their antagonists on
      canine oocyte maturation.

PMID- 19754584
TI  - In vitro compaction of germinal vesicle chromatin is beneficial to survival of
      vitrified cat oocytes.
AB  - The immature cat oocyte contains a large-sized germinal vesicle (GV) with
      decondensed chromatin that is highly susceptible to cryo-damage. The aim of the
      study was to explore an alternative to conventional cryopreservation by examining
      the influence of GV chromatin compaction using resveratrol (Res) exposure (a
      histone deacetylase enhancer) on oocyte survival during vitrification. In
      Experiment 1, denuded oocytes were exposed to 0, 0.5, 1.0 or 1.5 mmol/l Res for
      1.5 h and then evaluated for chromatin structure or cultured to assess oocyte
      meiotic and developmental competence in vitro. Exposure to 1.0 or 1.5 mmol/l Res
      induced complete GV chromatin deacetylation and the most significant compaction.
      Compared to other treatments, the 1.5 mmol/l Res concentration compromised the
      oocyte ability to achieve metaphase II (MII) or to form a blastocyst. In
      Experiment 2, denuded oocytes were exposed to Res as in Experiment 1 and cultured
      in vitro either directly (fresh) or after vitrification. Both oocyte types then
      were assessed for meiotic competence, fertilizability and ability to form
      embryos. Vitrification exerted an overall negative influence on oocyte meiotic
      and developmental competence. However, ability to reach MII, achieve early first
      cleavage, and develop to an advanced embryo stage (8-16 cells) was improved in
      vitrified oocytes previously exposed to 1.0 mmol/l Res compared to all
      counterpart treatments. In summary, results reveal that transient epigenetic
      modifications associated with GV chromatin compaction induced by Res is fully
      reversible and beneficial to oocyte survival during vitrification. This approach
      has allowed the production of the first cat embryos from vitrified immature
      oocytes.

PMID- 19754585
TI  - Relationship between motility and mitochondrial functional status in canine
      spermatozoa.
AB  - Inner mitochondrial membrane potential (IMM) is considered a sensitive indicator
      for the energetic status and motility of spermatozoa. The relationship between
      sperm motility parameters evaluated by Computer Assisted Sperm motility Analyzer
      and plasma membrane integrity and IMM assessed by triple staining (PI/SYBR-14 and
      JC-1) was evaluated in 10 dogs of unknown fertility. Sperm motility showed large
      variations ranging from 10% to 98%. Proportion of viable sperm cells and of
      spermatozoa with high IMM ranged from 74% to 99% and from 53% to 87%,
      respectively. The presence of a high IMM assessed by JC-1 was more strongly
      correlated to sperm viability (r = 1) than to sperm motility (r = 0.778). Our
      results indicate that JC-1 is suitable for detection of IMM changes in canine
      spermatozoa, but it should always be associated with an objective motility
      analysis to avoid incorrect evaluation of potential sperm fertility. Ejaculates
      with a low motility rate showed an unexpectedly high proportion of sperm with
      high IMM, suggesting that mitochondrial respiration could not be sufficient to
      support sperm motility, although it may be important for sperm survival in the
      female genital tract.

PMID- 19754586
TI  - Concentrations of prolactin, LH, testosterone, TSH and thyroxine in normospermic
      dogs of different breeds.
AB  - Concentrations of prolactin (PRL), LH, testosterone (T), TSH and thyroxine (T(4))
      were determined before and at 20, 120 and 180 min after a single iv injection of
      thyrotropin-releasing hormone (TRH) in eight Beagles, eight Fox Terriers, six
      Labrador Retrievers and five Great Danes that were normospermic. Mean basal PRL
      concentrations were lower in the Fox Terriers compared with the Great Danes (p <
      0.05). Mean LH concentrations were higher in the Fox Terriers than in the
      Beagles, and T was lower in the Fox Terriers at some times but not others (p <
      0.05). Thyroid Stimulating Hormone (TSH) concentrations did not differ among
      breeds, while mean basal T(4) values were lower in Fox Terriers compared with
      Labrador Retrievers and Great Danes (p < 0.05). Stimulation of T(4) secretion 120
      and 180 min after iv TRH injection was most pronounced in the Beagles and less in
      the Fox Terriers (p < 0.05). The results of the present study indicate that
      potential breed differences in circulating concentrations of PRL, LH, T, TSH and
      T(4) in male dogs with apparently normal fertility can be encountered, but
      further studies are needed to determine whether the observed differences are
      typical features of these breeds, reflect subsets of dogs within breeds, or are
      in part because of possible uncontrolled parameters such as sample timing,
      ambient photoperiod, housing conditions or diet.

PMID- 19754587
TI  - Osteopontin in seminal plasma and sperm membrane of dogs.
AB  - The objective of this work was to describe the presence of osteopontin (OPN) in
      canine seminal plasma and sperm membranes. A pool of seminal plasma and sperm
      membrane extract from 30 dogs was used. Polyacrylamide electrophoresis gels were
      performed and the bands were transferred to nitrocellulose paper and Western blot
      was undertaken using an antibody anti-OPN. Two and 12 bands were marked in the
      seminal plasma (77.2 and 15.6 kDa) and sperm membrane extracts (70.6-26.6 kDa),
      respectively. However, from 12 marked bands in the sperm membrane extract, only
      three (46.4, 37.7 and 36.5 kDa) were strongly marked. We conclude that, seminal
      plasma and sperm membranes from dogs contain different isoforms of OPN; yet,
      further studies will be necessary to determine their function in this species.

PMID- 19754588
TI  - Seasonal changes in testicular cell morphology in domestic male cats (Felis
      catus).
AB  - The aim of this study was to asses the variation in the morphology of the seminal
      epithelium in relation to natural photoperiod in male cats. Tom cats (n = 240)
      were castrated every other week throughout the year. Each testis was fixed in
      Bouin's solution and cut into sections. The percentage of tubules with round
      spermatids (RS), elongated spermatids (ES), tailed spermatids (TS), mature
      spermatids (MS) and the number of Sertoli cells (SC) and Leydig cells (LC) were
      recorded in each sample. Testicles from males during short days (SHD) had a
      higher percentage of tubules with RS and ES compared to testicles from males
      during long days (LHD, 31.3 +/- 0.6 vs 2.1 +/- 0.6%, p < 0.001; 30.9 +/- 0.7 vs
      11.0 +/- 0.7%, p < 0.001). Conversely, testicles from males during SHD had a
      lower percentage of tubules with TS and MS compared to testicles from males
      during LHD (24.5 +/- 0.8 vs 29.7 +/- 0.8%, p < 0.01; 13.1 +/- 1.2 vs 57.0 +/-
      1.2%, p < 0.01). Furthermore, testicles from males during SHD had a higher number
      of SC and lower number of LC compared to testicles from males during LHD (11.4 +/
      0.1 vs 8.0 +/- 0.1%, p < 0.01; 19.2 +/- 1.0 vs 38.0 +/- 1.0%, p < 0.01). In
      conclusion, there are seasonal changes in testis cell morphology in the tom which
      may be related to seasonal sperm production.

PMID- 19754589
TI  - Plasma hormone levels and semen quality in male cats during non-breeding and
      breeding seasons.
AB  - Female cats are known to be seasonal breeders and male cats annual breeders.
      Despite this, there are limited data on the influence of breeding season (BS) on
      hormone concentration and semen quality in the male cat. This study compared
      plasma concentrations of LH and testosterone (T), and semen quality during the
      non-breeding season (NBS) and BS in five male cats subject to natural hours of
      daylight but a constant environmental temperature. Plasma LH and T concentrations
      were higher during the BS in 2/35 and 3/5 cats, respectively, although when
      comparing both hormones combined, values were higher during the BS than the NBS
      in all cats (p < 0.01). There were no significant differences in the percentage
      of abnormal sperm between the cats. Overall, semen quality was superior during
      the BS with larger semen volume in 2/5, sperm motility in 2/5 and sperm viability
      in 3/5 cats. Although there was a clear seasonal effect on hormone secretion and
      semen quality, during the NBS all cats were likely to have been fertile.

PMID- 19754590
TI  - Localization of oestrogen receptors in the epididymis during sexual maturation of
      the domestic cat.
AB  - Oestrogens are involved in regulation of spermatogenesis and sperm maturation and
      are essential for male fertility. To study the role of oestrogens on epididymal
      function in the domestic cat, we analyzed the localization patterns of oestrogen
      receptors (ERs) within the epididymis of juvenile, pubertal and adults using
      immunohistochemistry. Cat epididymal tissues obtained during routine castrations
      were fixed in chilled Bouin's solution and processed for immunohistochemistry
      with ER-specific antibodies. For a certain receptor type, ER localization was
      influenced by donor age. In the juvenile epididymis, ERalpha was localized in the
      nuclei of epithelial cells of efferent ducts and undifferentiated epithelium of
      the ductus epididymis. During puberty, ERalpha localization in the
      undifferentiated epithelium of the epididymis shifted from the nuclei to the
      cytoplasm and plasma membrane. Oestrogen receptor-alpha level was highest in the
      pubertal and adult epididymis, especially within the cytoplasm and in plasma
      membranes of caput epithelial cells. This finding was suggestive of a role in
      fluid reabsorption within the efferent ducts and the epididymis. In corpus and
      cauda regions, ERalpha was less abundant, suggesting a minor role for oestrogens
      in sperm storage areas. Interestingly, localization of ERbeta was neither
      influenced by age nor location within the epididymis and was ubiquitous
      throughout. Results demonstrate that oestrogen actions within the epididymis may
      be predominantly mediated through ERalpha during sexual maturation in the
      domestic cat.

PMID- 19754591
TI  - Recrudescence of spermatogenesis in the dog following downregulation using a slow
      release GnRH agonist implant.
AB  - The present study examined the degree to which downregulation with a GnRH agonist
      impaired spermatogenesis and the time course of morphological and hormonal
      changes that occurred during recrudescence of spermatogenesis. Using a control
      group (group 1, n = 5) of dogs, the effect of a removable slow release GnRH
      agonist implant was investigated in beagle dogs (group 2, n = 30). The implant
      was removed after 5 months (week 0) and three to four dogs were castrated at
      weeks 0, 3, 6, 9, 12, 15, 18, 21 and 24. The degree of downregulation and
      recrudescence of spermatogenesis was assessed by evaluation of 200 tubular cross
      sections, resulting in an assigning of dogs of group 2 to testis developmental
      groups (DG) according to the most developed germ cell observed: DG A,
      spermatocytes; DG B, round spermatids; DG C, elongating spermatids and DG D,
      elongated spermatids. Downregulation led to an arrest of spermatogenesis at the
      level of spermatogonia/primary spermatocytes. The time course of recrudescence
      showed high individual variations and the number of dogs falling into DG A, B, C
      and D was 4, 3, 6 and 17 respectively. Spermatogenesis in group 2, DG D was not
      different from group 1 (control). In DG A, mean area of Leydig-cell nuclei was
      lower (p < 0.001) than in the other DG and group 1 and resembled that of juvenile
      dogs (group 3, n = 3); nuclei of Sertoli cells had changed from more
      flat/polygonal (group 1, group 2, DG C and D) to round/ovoid and had moved to a
      more luminal position. As indicated by basal testosterone (T), luteinizing
      hormone (LH) and follicle stimulating hormone (FSH) concentrations at implant
      removal, full downregulation had been obtained. Testosterone, LH and FSH
      concentrations [X(g) (DF), ng/ml] increased (p < 0.05) from implant removal to DG
      B [T: 0.1 (1.24) vs 2.12 (2.31); LH: 0.2 (2.15) vs 1.11 (1.7); FSH: 0.37 (3.50)
      vs 6.37 (1.68)] and were more or less constant thereafter indicating that onset
      of spermatogenesis was related to an increase of plasma T occurring in a very
      narrow time window. Following GnRH implantation, the size of the testes and the
      prostate decreased by approximately 55% (p < 0.001), they increased to sizes
      similar to pre-treatment values following implant removal.

PMID- 19754592
TI  - Effect of progesterone and ionomycin on domestic cat sperm motility patterns and
      acrosome reaction.
AB  - This study was aimed at assessing the changes in sperm motion patterns and the
      percentage of acrosome reaction (AR) in domestic cat semen after treatment with
      either ionomycin or progesterone (P(4)). Ten ejaculates were collected from five
      tomcats using an artificial vagina, and were diluted, centrifuged and resuspended
      in a capacitation medium. Samples were evaluated and divided into seven equal
      aliquots and, after 2 h at 25 degrees C, were incubated for 30 min at 38 degrees
      C in 5% CO(2) and then analyzed. Computer-assisted sperm analysis and a
      combination of three fluorescent probes were used to assess sperm plasma,
      acrosomal membrane integrity and mitochondrial transmembrane potential. Thirty
      minutes after the start of incubation, P(4) was added (10 microg/ml) to the P1
      group. Groups P2 and P3 were supplemented with P(4) (10 and 20 microg/ml,
      respectively) only after 2 h of incubation, and groups I1 and I2 were
      supplemented with ionomycin (4 and 8 mum, respectively) 2 h after incubation.
      Group E was supplemented with ethanol (0.6%) at 2 h after incubation and group C
      received no supplementation. Ionomycin and P(4) treatments led to a
      hyperactivation-like sperm motion and an increase (p < 0.05) in the percentage of
      AR. Although a higher (p < 0.05) percentage of AR was obtained in group I2 when
      compared with all P(4) groups, a decrease (p < 0.05) in total and progressive
      motility was observed in I2 group. As I1 group was similar to I2 to induce AR
      without diminishing sperm motility, we can conclude that ionomycin at 4 microm
      seems to be more suitable to trigger AR in domestic cat sperm.

PMID- 19754593
TI  - Effect of daily food supplementation with essential fatty acids on canine semen
      quality.
AB  - Polyunsaturated fatty acids are important membrane components that influence
      membrane integrity and fluidity. In the present study, the effect of oral
      supplementation for 60 days with essential fatty acids (omega 3, 6 and 9) and
      vitamin E on canine semen quality was evaluated. Sixteen dogs were selected for
      the experiment; eight were used as the control group and eight received the fatty
      acid supplemented diet for 60 days. Semen samples were taken every 15 days during
      the entire experimental period and were analyzed for volume (ml), motility (%),
      vigour (0-5), concentration (x10(6)/ml), morphology of spermatozoa (%), plasma
      membrane integrity (%; using the hyposmotic swelling test) and thermoresistance
      (motility and vigour after 4 h at 38 degrees C). We concluded that, daily
      supplementation with omega 3, omega 6 and omega 9 fatty acids, together with
      vitamin E, for a period of 60 days, significantly increased the semen volume of
      the treated group after 15 days of supplementation; the vigour and concentration
      of spermatozoa were superior after the first month of supplementation, while the
      percentage of morphologically abnormal spermatozoa decreased and the cells were
      protected against thermal stress.

PMID- 19754594
TI  - Comparison of the effect of the aromatase inhibitor, anastrazole, to the
      antioestrogen, tamoxifen citrate, on canine prostate and semen.
AB  - This study compared the efficiency of the aromatase inhibitor, anastrazole, with
      the antioestrogenic receptor blocker, tamoxifen, on normal (NRL) and hyperplastic
      prostate glands. Forty healthy dogs were classified as NRL (n = 18) or abnormal
      (ABN) with benign prostate hyperplasia (n = 22). The dogs were randomly assigned
      to one of the following six groups, treated for 60 days; oral placebo for normal
      (NRL-PLC; n = 6) and abnormal (ABN-PLC; n = 6), oral anastrazole 0.25-1 mg/day,
      for normal (NRL-ANZ, n = 6) and abnormal (ABN-ANZ, n = 8) and oral tamoxifen
      citrate 2.5-10 mg/day for normal (NRL-TMX; n = 6) and abnormal (ABN-TMX; n = 8)
      dogs. The dogs were evaluated before treatment and then monthly for 4 months. At
      the end of the treatment, the prostatic volume decreased by 28.5 +/- 4.3%, 21.6
      +/- 6.3% and 0.7 +/- 1.0% in the ABN-TMX, ABN-ANZ and ABN-PLC (p < 0.01),
      respectively. From then on, prostatic volume began to increase without reaching
      pre-treatment values at the end of the study. In the ABN animals, there were no
      differences for this parameter between ANZ and TMX treatment (p > 0.1), whereas
      in the NRL animals ANZ produced a less pronounced decrease (p < 0.05), libido,
      testicular consistency and scrotal diameter decreased during treatment in the TMX
      group (p > 0.05). These parameters and sperm volume, count, motility and
      morphological abnormalities remained unaltered throughout the study in the ANZ
      and PLC groups (p > 0.05). There were no haematological nor biochemical side
      effects. Anastrazole might offer a safe and effective alternative for the medical
      management of dogs with benign prostatic hyperplasia.

PMID- 19754595
TI  - Effects of short-term hyper- and hypoprolactinaemia on hormones of the pituitary,
      gonad and -thyroid axis and on semen quality in male Beagles.
AB  - Effects of a short-term hyper- and hypoprolactinaemia on serum concentrations of
      LH, testosterone and semen quality in six male Beagles were investigated. Blood
      samples were collected at 3-day intervals for 12 weeks. The time span was divided
      into five 3-week periods: pre-treatment, metoclopramide (MCP) treatment (0.2
      mg/kg orally three times daily), cabergoline (CAB) treatment (5 microg/kg orally
      once daily), post-treatment 1 and post-treatment 2. In the latter, only semen
      characteristics were evaluated. Semen parameters were analyzed once per week
      during the whole 15-week investigation time. At the end of each period, the
      effects of a single intravenous injection of thyrotropin-releasing hormone (TRH;
      10 microg/kg) on the secretion of prolactin (PRL), LH, testosterone, thyroid
      stimulating hormone and thyroxine (T4) were investigated. Pre-treatment serum PRL
      concentration increased under MCP (p < 0.05), followed by a decrease under CAB
      administration (p < 0.05). Luteinizing hormone and testosterone concentrations
      were not affected. Except for straight-line sperm velocity, semen quality did not
      differ between collection periods. A single iv TRH injection induced a
      significant PRL increase at 20 min in all experimental periods except during CAB
      treatment. Luteinizing hormone and testosterone did not show clear TRH-related
      changes. Basic T4 levels were significantly reduced after CAB treatment (p <
      0.05). The results of the present study demonstrate that MCP-induced short-term
      hyperprolactinaemia in male beagles does not seriously affect the hypothalamo
      pituitary axis and semen quality.

PMID- 19754596
TI  - Ultrasound as a mechanical method for male dog contraception.
AB  - Therapeutic ultrasound (1.5 W/cm(2)) was investigated for its effect upon
      testicular size and consistency and semen quality in five dogs. Dogs were treated
      every other day with a total of three treatments and were examined up to 2 weeks
      after treatment. There was some tenderness after treatment and a significant
      decrease in testicular size and semen quality. This method may provide a suitable
      contraception technique in dogs and requires further investigation.

PMID- 19754597
TI  - Clinical use of testicular fine needle aspiration cytology in oligozoospermic and
      azoospermic dogs.
AB  - Clinical investigation of canine testicular function is complicated by the
      difficulty in the evaluation of seminiferous tubules. Until recently, testicular
      biopsy was the only diagnostic option for dogs with persistent oligo/azoospermia.
      In human andrology, testicular fine needle aspiration (TFNA) is currently
      considered a useful method in the evaluation of azoospermia and severe
      oligozoospermia, and has long replaced classical biopsy to evaluate
      spermatogenesis. In order to verify its diagnostic efficacy for the clinical
      approach to canine oligo- or azoospermia, TFNA was performed in seven adult (two
      oligozoospermic and five azoospermic) dogs. After sedation, a fine (21-23 gauge)
      butterfly needle connected to a 50-ml syringe was inserted into each testicle;
      strong suction was applied and the aspirated fluid squirted on a glass slide,
      smeared out, air-dried and stained with a modified May-Grunwald-Giemsa. Under
      light microscopy, Sertoli cells (all those found in each investigated field) and
      spermatogenic cells (n = 100) were counted on each smear in order to
      differentiate spermatogonia, primary spermatocytes, secondary spermatocytes,
      early spermatids, late spermatids and spermatozoa, and calculate their relative
      percentages. Cytological analysis showed the following testicular pictures:
      normal spermatogenesis (compatible with obstruction of the seminal ducts),
      hypospermatogenesis, maturative disturbances and Sertoli cell-only syndrome. Two
      dogs with an obstructive lesion were treated with corticosteroids; one of them
      recovered and sired two litters of puppies.

PMID- 19754598
TI  - Prostatic perfusion in the dog using contrast-enhanced Doppler ultrasound.
AB  - Ultrasonography has become the imaging modality of choice for evaluation of the
      prostate gland in the dog. Unfortunately, despite providing excellent images, it
      may be difficult to differentiate the common canine prostatic diseases with
      ultrasound because many have a similar ultrasonographic appearance. Real-time
      contrast-enhanced ultrasound was used to monitor and characterise the normal
      perfusion pattern and perfusion dynamics of the canine prostate gland when using
      a micro bubble contrast agent. In all contrast studies, the prostatic artery,
      entered the prostate gland on the dorso-lateral surface then tunnelled into the
      prostatic capsule and branched into many small parenchymal arteries which were
      directed medially towards the urethra to supply the body of the prostate gland.
      The flow of the contrast medium into the prostatic parenchyma was visible after
      15 s. During the wash-in phase, there was an homogenous enhancement of the
      prostatic parenchyma. During the wash-out phase, an homogenous decrease of the
      echogenicity was visible in all cases.

PMID- 19754599
TI  - Cryopreservation of canine semen - new challenges.
AB  - Egg yolk (EY) protects cell membranes against cold shock, and it prevents or
      restores the loss of phospholipids from the membrane. EY has been widely used in
      semen extenders. It has been added to Tris-Glucose buffer and has been widely
      used for cooling and cryopreservation of canine semen. EY is not a defined
      entity, but a complex biological compound containing proteins, vitamins,
      phospholipids, glucose and antioxidants which are all potentially useful for cell
      membrane integrity. Unfortunately, it also is a biologically hazardous compound.
      Hence, whole EY needs to be replaced by other chemically defined components for
      semen processing in dogs. Freezing poor semen does not improve its quality, so
      attention must be focused on how to cope with dogs whose semen does not freeze
      well, and on designing individual freezing extenders for semen from such males.
      Furthermore, differences have been found among canid species in the ability of
      their spermatozoa to withstand freezing. There are differences in sperm membrane
      fatty acid composition among species, which may explain part of these
      differences. If the presence of long-chained polyunsaturated fatty acids
      contributes to increased membrane fluidity, this relationship may be biphasic,
      i.e. either too much membrane fluidity, or too little, could compromise
      successful sperm cryopreservation. An increase in fluidity of the outer leaflet
      of the plasma membrane has been shown in frozen thawed dog spermatozoa. The
      protective effect of exogenous lipids may lie in close association with the
      membrane rather than in modification or rearrangement of the membrane. This also
      points at lipids as an important, if not entirely new group of substances, which
      may substitute standard EY-based diluents in preserving sperm survival during
      freezing. EY-derived phospholipids or lecithin could be used to replace whole EY.
      Vegetable lecithin is currently investigated to avoid using substances of animal
      origin. EY also contains antioxidants which prevent cells from oxidative damage
      due to the generation of reactive oxygen species. An increasing number of
      publications now recognize the significance of protecting sperm from this damage
      during processing by using dietary or diluent supplemented antioxidants. This
      paper aims at looking at some of the new challenges in freezing of dog semen.

PMID- 19754600
TI  - Fertilizing capacity of frozen epididymal sperm collected from dogs.
AB  - The collection of epididymal sperm may be a valuable tool for canine reproduction
      especially since it can enable collection of cells after death of a valuable dog.
      The aim of the present study was to evaluate the viability of epididymal sperm
      after freeze-thawing. Epididymides were obtained from four adult dogs by elective
      orchiectomy. The caudal portion of the epididymides and part of the deferential
      ducts were squeezed by means of an anatomic clamp into a Petri dish containing
      either 0.9% saline solution (Group 1) or Ringer solution without lactate (Group
      2). Samples were centrifuged at 800 x g for 10 min, the supernatant was removed
      and the pellet was diluted in one step with a Tris/citric acid/OEP (Orvus Es
      Paste) extender containing 7% glycerol and subjected to semen freezing. Oocytes
      were obtained from canine ovaries, after ovariohysterectomy. Only oocytes that
      were approximately 100 mum in diameter, with a dark ooplasm surrounded by three-
      or four-well formed cumulus cell layers were used for sperm testing. Frozen semen
      samples were thawed in a water bath at 70 degrees C for 8 s and analysed at room
      temperature for sperm motility and velocity. Oocytes were incubated with
      spermatozoa in humidified atmosphere containing 5% CO(2) at 38 degrees C for 18
      h. Morphological and functional characteristics of spermatozoa were similar in
      both groups. However, the percentage of sperm cells bound to oocytes was
      significantly higher in Group 2 than in Group 1. This result suggests that the
      Ringer solution without lactate was a more suitable medium for collecting
      epididymal canine sperm than 0.9% saline.

PMID- 19754601
TI  - TRIS-lecithin extender supplemented with antioxidant catalase for chilling of
      canine semen.
AB  - The aims were to evaluate the suitability of a non-commercial TRIS-lecithin (LC)
      extender and the effect of different concentrations of catalase (CAT) on
      motility, capacitation status (Chlortetracycline-assay) and zona pellucida (ZP)
      binding capacity of canine spermatozoa stored at +5 degrees C for 4 days. The
      sperm-rich fractions of the ejaculates of four stud dogs were divided into four
      aliquots. After centrifugation, sperm pellets were diluted (200 x 10(6) sperm/ml)
      in TRIS buffer, citric acid, fructose, antibiotics, supplemented with 20% egg
      yolk (TRIS-EY) or 0.04% soybean lecithin (TRIS-LC) with CAT (150 or 450 UI/ml) or
      without CAT, and then preserved at 5 degrees C for 4 days. The results showed
      that LC is a valid alternative to EY for chilling canine semen, as similar rates
      of motility, number of uncapacitated spermatozoa and of spermatozoa binding the
      oocyte ZP were obtained in semen chilled in TRIS-LC or TRIS-EY. Different
      concentrations of CAT in a TRIS-LC based extender did not improve the quality of
      semen after chilling. However, a concentration of 150 UI/ml CAT resulted in an
      increased number of spermatozoa bound to the oocyte ZP, after 4 days of chilling
      when compared to semen chilled with TRIS-EY and TRIS-LC. In conclusion, an animal
      protein-free extender with soybean LC, as a replacement of EY, is suitable for 4
      days chilling of canine spermatozoa, but the addition of CAT does not improve
      general semen quality except for a slight effect on sperm-ZP binding.

PMID- 19754602
TI  - Western blot analysis of proacrosin/acrosin in frozen dog sperm during in vitro
      capacitation.
AB  - Acrosin is an acrosomal protease synthesized as an inactive precursor,
      proacrosin, which is processed via autoproteolysis into active forms alpha- and
      beta-acrosin. In this paper, a comparative study on the immunoreactivity of
      acrosin during in vitro capacitation of frozen and fresh (control) canine sperm
      using Western blot analysis is reported. Semen samples were obtained by digital
      stimulation and ejaculates processed as fresh and frozen samples and then
      capacitated for 0, 30, 60 and 90 min. At each time period, samples were analyzed
      with monoclonal antibody C5F10 by Western blot. The antibody specifically
      recognized, in fresh and frozen/thawed spermatozoa, a 40-, 32- and 27-kDa bands
      corresponding to proacrosin, alpha- and beta-acrosin, respectively, during
      capacitation. Western immunoblots showed that the beta-acrosin reactivity in
      fresh sperm was directly proportional to the time of capacitation, whereas a
      decreased reactivity of active form of acrosin was observed with frozen-thawed
      sperm (p < 0.05). These results suggest that proacrosin is activated to beta
      acrosin earlier in frozen/thawed dog spermatozoa than in fresh dog spermatozoa.

PMID- 19754603
TI  - Effect of different concentrations of ascorbic acid on motility, membrane
      integrity and chromatin status of frozen-thawed canine spermatozoa within six
      hours of storage at 37 degrees C.
AB  - The aim of this study was to examine comprehensively the effect of ascorbic acid
      (Asc) on frozen-thawed canine semen. Pooled ejaculates (n = 10) were assessed for
      quality with a computer-assisted sperm analyser (CASA). After centrifugation, the
      semen was divided into four aliquots (A-D) of which three were diluted with
      Uppsala 1 extender (v/v) containing different concentrations of Asc (B: 6.8
      mmol/l; C: 13 mmol/l; D: 27 mmol/l). One group without Asc served as control (A).
      Subsequently, dilution samples were treated and cryopreserved as described
      previously (Theriogenology 66, 2006, 173). After thawing, samples were stored at
      37 degrees C for 1, 3 and 6 h, then examined for quality (CASA, flow cytometry,
      sperm chromatin structure assay; SCSA). Staining for flow cytometry was performed
      with FITC-PNA and propidium iodide (Reproduction 128, 2004, 829). The SCSA was
      performed with both Tris-NACL-EDT buffer (TNE)- and Tris-fructose-citrate buffer
      (TFC). In the Asc-supplemented groups, percentages of progressively motile sperm
      (P) were significantly lower than in the control group (A 1 h: 56.6 +/- 9.8, 6 h:
      18 +/- 4.5; B 1 h: 51.2 +/- 11.8, 6 h: 13.6 +/- 5; C 1 h: 41 +/- 16.2, 6 h: 11.2
      +/- 6.1; D 1 h: 37 +/- 15.2, 6 h: 8.6 +/- 5; p < 0.01), whereas, the percentages
      of intact cells without acrosome reactions did not differ between groups (p >
      0.05). Furthermore, there were no significant differences between TNE- and TFC
      samples, for alphaT, for SD of alphaT or for comp alphaT [comp alphaT: TCF-A: 2.5
      +/- 1.7%, TNE-A: 3.4 +/- 3.2%; TCF-D: 2.5 +/- 2%, TNE-D: 3.3 +/- 4.3%; p > 0.05].
      However, samples diluted with both extenders correlated concerning alphaT, but
      not comp alphaT. We therefore recommend using TNE-buffer for SCSA with
      cryopreserved canine semen. In addition, the average alphaT values did not differ
      significantly between the controls and all other groups (TNE-A: 380.2 +/- 89.1;
      TNE-D: 338.1 +/- 137.4; p > 0.05). It can be concluded that addition of Asc to
      cryoextender does not increase quality of frozen-thawed canine semen.

PMID- 19754604
TI  - Influence of ascorbic acid and glutathione antioxidants on frozen-thawed canine
      semen.
AB  - Poor sperm viability post-thaw has resulted in constant research into methods of
      cryopreservation of canine semen. One factor that may be involved in poor
      viability is sperm oxidative stress caused by excessive formation of reactive
      oxygen species. The present study was performed in order to evaluate the effect
      of different concentrations of ascorbic acid (AA) and glutathione (Glu) added to
      an extender for the freeze-thawing of dog sperm. Semen from five mature dogs was
      collected and frozen in two studies. Prior to and after freezing, sperm motility,
      morphology and membrane status were examined. In addition, sperm motility was
      examined up to 120 min after thawing to evaluate thermo-resistance. In study I,
      semen was collected twice from each dog. On both occasions, semen was divided
      into three aliquots: control, Glu 1 mM and Glu 5 mM. In study II, semen was
      collected twice and divided into three aliquots; control, AA 50 microM and AA 250
      microM. Initial sperm motility was significantly higher in sperm diluted with AA
      50 microM; sperm longevity, however, measured by a thermal-resistance test (TRT),
      was higher for Glu treatments. Higher concentration of Glu produced significant
      improvement in TRT and membrane status, whereas higher concentration of AA had a
      negative impact in sperm longevity. Antioxidant supplementation to semen freezing
      extenders improved semen quality post-thaw. Moreover, Glu had the most beneficial
      effect when supplemented at 5 mM.

PMID- 19754605
TI  - Effects of the inclusion of Equex STM into Tris-based extender on the motility of
      dog spermatozoa incubated at 5 degrees C.
AB  - The aim of this study was to estimate the effects of Equex STM on sperm motion
      characteristics in chilled dog semen extended in Tris-based diluent. Thirty-two
      ejaculates were collected from 12 proven German shepherd stud dogs. The sperm
      rich fractions were diluted in Tris-based extender with 1% (v/v) Equex STM
      (sample A) and in Tris-based extender with no addition of detergent (sample B).
      The extended semen was incubated for 240 h at 5 degrees C and the motility
      parameters were evaluated by CASA system at 24-h intervals. Addition of Equex STM
      to Tris-based extender led to an initial activation of motion activity of
      spermatozoa, followed by a rapid decrease, shortening the lifespan of spermatozoa
      incubated at 5 degrees C. Computer-assisted sperm analysis clearly showed that
      Equex STM-induced changes of sperm motion characteristics resemble the
      hyperactivation (HA) of spermatozoa associated with the capacitation process.

PMID- 19754606
TI  - Impact of 24-h cooling prior to freezing on the survival of domestic cat (Felis
      catus) epididymal sperm.
AB  - The aim of this study was to investigate the impact of a 24-h cooling period
      prior to freezing on domestic cat epididymal sperm viability. Fifteen tomcats
      were submitted to routine orchiectomy and sperm samples were retrieved from both
      epididymides in a Tris-glucose-20% egg yolk extender. For each tomcat, the
      diluted sperm was split into two equal volumes and cooled to 5 degrees C at a
      rate of 0.5 degrees C/min; one sample for 60 min (control) and the other for 24 h
      (cooled). After the cooling period, samples from both groups were frozen using an
      identical freezing protocol. Sperm samples were evaluated in three different
      periods: immediately after harvesting, after cooling at 5 degrees C for 24 h
      (cooled group) and after freezing-thawing of control and cooled groups.
      Evaluations consisted of sperm motility and progressive status, sperm morphology
      and plasma membrane integrity (PMI) using two fluorescent probes. After cooling
      for 24 h, a decrease (p < 0.05) in sperm motility, progressive status and PMI was
      observed when compared to sperm samples immediately after collection. Comparing
      the results obtained after thawing, no difference (p < 0.05) was found regarding
      sperm motility, progressive status, PMI and sperm morphology between control and
      cooled groups. The results from the present study show that cooling cat
      epididymal spermatozoa at 5 degrees C for 24 h prior to freezing does not lead to
      major damage of spermatozoa impairing the freeze-thaw process.

PMID- 19754607
TI  - Effect of catalase and superoxide dismutase on motility, viability and acrosomal
      integrity of frozen-thawed cat spermatozoa.
AB  - The aim of this study was to evaluate the effect of antioxidant catalase (CAT)
      and superoxide dismutase (SOD) in semen extender on motility, viability and
      acrosomal integrity of frozen-thawed cat spermatozoa. Semen was collected by
      using an artificial vagina from five domestic cats (two ejaculates/cat).
      Spermatozoa were diluted in egg yolk Ttris-fructose citrate solution (EYT-FC)
      without glycerol and cooled at 4 degrees C for 1 h, then diluted further with EYT
      FC with glycerol (7% final concentration) and 400 IU/ml of CAT (treatment 1) or
      SOD (treatment 2) or without antioxidants (control). Before freezing using a
      styrofoam box, diluted spermatozoa filled in 0.25-ml straws were equilibrated for
      1 h at 4 degrees C. After thawing, spermatozoa were assessed for motility,
      viability and acrosomal integrity. Cryopreservation significantly impaired sperm
      motility, viability and acrosomal integrity (p < 0.05). However, motility,
      viability and acrosomal integrity of frozen-thawed cat spermatozoa in the EYT-FC
      with CAT, SOD and without the antioxidants were not significantly different. The
      average percentages of spermatozoa motility after thawing compared between
      control, treatment 1 and treatment 2 group were 43.5 +/- 3.2, 42 +/- 4.1 and 38
      +/- 4.5; for viability: 44.8 +/- 3.5, 50.6 +/- 5.7 and 47.1 +/- 4.1 and for
      acrosomal integrity: 45 +/- 3.5, 44.9 +/- 3.4 and 44.4 +/- 3.3, respectively. In
      conclusion, adding CAT and SOD to EYT-FC did not improve motility, viability and
      acrosomal integrity in cryopreserved cat spermatozoa.

PMID- 19754608
TI  - Detection of lipid peroxidation reaction in frozen-thawed epididymal cat
      spermatozoa using BODIPY(581/591) C11.
AB  - Lipid peroxidation is considered to be an important cause of sperm membrane
      damage, resulting in an apparent reduction of reproductive fecundity. Recently, a
      new lipophilic fluorescent dye probe (BODIPY(581/591) C11; Invitrogen Singapore
      Pte Ltd, Singapore) has been demonstrated to be a highly sensitive indicator for
      the physiological oxidation of cell membrane fatty acids. The objectives of this
      study were: (i) to detect lipid peroxidation in frozen-thawed epididymal cat
      spermatozoa using the BODIPY(581/591) C11 and (ii) to study the effect of semen
      extender in protecting sperm membrane from lipid peroxidation [100-mm ferrous
      ion, ferrous sulphate (FeSO(4))]. Epididymal cat spermatozoa were collected from
      eight male cats. Two straws of sperm sample from each cat were cryopreserved.
      After thawing, the semen extender from the first straw was removed and the sperm
      pellet was resuspended with Tris buffer (control). The semen sample from the
      other straw was equally divided: one sample contained semen extender (treatment
      A) and one contained no extender (treatment B); both were incubated with FeSO(4).
      Semen samples were labelled with the BODIPY(581/591) C11 probe and evaluated by
      flow cytometry at 0 and 6 h after thawing (control), 6 h after the addition of
      FeSO(4) (treatment A), and 30 min and 6 h after the addition of FeSO(4)
      (treatment B), respectively. The percentage of lipid peroxidation was higher
      after treatment B (51.3 +/- 23.9) and 6-h incubation compared with the control
      and treatment A (p < 0.05). Furthermore, the percentage of lipid peroxidation
      after treatment B increased during the incubation time (p < 0.05). In conclusion,
      the high percentage of lipid peroxidation after treatment B indicated that
      FeSO(4) induced membrane damage in cat spermatozoa, which could be detected by
      BODIPY(581/591) C11. This marker is suggested to be a beneficial tool for the
      evaluation of lipid peroxidation. Furthermore, the use of semen extender seemed
      to protect cat spermatozoa membranes from lipid peroxidation.

PMID- 19754609
TI  - Survival of frozen-thawed cat spermatozoa pre-cooled in the epididymides.
AB  - Sperm recovery from epididymides and their cryo-preservation require particular
      media and equipment not always available in the field. This study aimed to
      compare the quality of frozen-thawed epididymal cat spermatozoa pre-cooled in an
      extender vs. cooled in the epididymides. Testes with attached epididymides from
      23 cats subjected to routine orchidectomy were allocated into two groups; 2-day
      (n = 10) and 4-day cold storage (n = 13). Spermatozoa from one epididymis of each
      pair were recovered, evaluated, extended in a Tris egg yolk extender, cooled to 5
      degrees C and stored for either 2 or 4 days prior to freezing (Treatment 1). The
      remaining testis attached with the epididymis was stored at 5 degrees C in a Tris
      buffered solution for either 2 or 4 days, before the spermatozoa were harvested,
      evaluated and frozen (Treatment 2). The spermatozoa were evaluated for percentage
      of motility, viability, intact acrosomal integrity and morphology. Sperm
      evaluations were performed prior to freezing and after freezing-thawing. The
      spermatozoa maintained in the epididymes yielded similar quality after cold
      storage and after freeze-thawing in comparison to that maintained in the extender
      at both storage times (p > 0.05). However, cold storage of spermatozoa for 4 days
      resulted in a reduction in motility compared to that cold stored for 2 days (p <
      0.05). Similarly, freezing of spermatozoa pre-cooled for 4 days resulted in lower
      percentages of motility, viability and intact acrosome than that pre-cooled for 2
      days (p < 0.05). A higher number of spermatozoa with simple bent tail and coiled
      tail were found in the samples maintained in the epididymides than in the
      extender after 4-day storage. The results indicated that cat spermatozoa can be
      cold stored in the epididymides prior to being harvested and cryopreserved in a
      distant laboratory. This technology is an alternative to rescue male gamete when
      animals are castrated or unexpectedly die under field conditions.

PMID- 19754610
TI  - Incubation of post-thaw epididymal cat spermatozoa with seminal plasma.
AB  - In domestic cats, epididymal spermatozoa have lower initial motility and
      viability than ejaculated spermatozoa and it is possible that seminal plasma
      compounds are behind these effects. The aim of this study was to investigate
      whether co-incubation of post-thaw epididymal cat spermatozoa with seminal plasma
      was able to improve sperm quality. Epididymal cat spermatozoa from 11 cats were
      cryopreserved. After thawing, each sperm sample was divided into two aliquots,
      centrifuged and incubated with two different media; Tris buffer (control) or
      pooled seminal plasma (treatment). Sperm quality was observed at 0, 2, 4 and 6 h
      after incubation. The results demonstrated that all of the sperm parameters
      except acrosome integrity were lower in the treatment group compared to the
      control group (p < 0.05); the percentages of motility (46.4 +/- 15.4 vs 40.0 +/-
      9.4), the scores of progressive motility (3.1 +/- 0.4 vs 2.8 +/- 0.5), the
      percentages of spermatozoa with intact plasma membrane (46.3 +/- 9.7 vs 39.6 +/-
      8.9) and intact acrosome (36.5 +/- 16.2 vs 32.9 +/- 15.1), as well as at all time
      points. In conclusion, the seminal plasma seems less beneficial to the post-thaw
      epididymal cat spermatozoa than the Tris buffer.

PMID- 19754611
TI  - Abstracts of the 14th Congress of the European Society for Organ Transplantation.
      August 30-September 2, 2009. Paris, France.

PMID- 19754612
TI  - ISPAD clinical practice consensus guidelines 2009 compendium. Introduction.

PMID- 19754613
TI  - Definition, epidemiology and classification of diabetes in children and
      adolescents.

PMID- 19754614
TI  - Phases of diabetes in children and adolescents.

PMID- 19754615
TI  - Type 2 diabetes in children and adolescents.

PMID- 19754616
TI  - The diagnosis and management of monogenic diabetes in children and adolescents.

PMID- 19754617
TI  - Management of cystic fibrosis-related diabetes in children and adolescents.

PMID- 19754618
TI  - Diabetes education in children and adolescents.

PMID- 19754619
TI  - The delivery of ambulatory diabetes care to children and adolescents with
      diabetes.

PMID- 19754620
TI  - Assessment and monitoring of glycemic control in children and adolescents with
      diabetes.

PMID- 19754621
TI  - Insulin treatment in children and adolescents with diabetes.

PMID- 19754622
TI  - Nutritional management in children and adolescents with diabetes.

PMID- 19754623
TI  - Diabetic ketoacidosis in children and adolescents with diabetes.

PMID- 19754624
TI  - Assessment and management of hypoglycemia in children and adolescents with
      diabetes.

PMID- 19754625
TI  - Sick day management in children and adolescents with diabetes.

PMID- 19754626
TI  - Exercise in children and adolescents with diabetes.

PMID- 19754627
TI  - Management of children and adolescents with diabetes requiring surgery.

PMID- 19754628
TI  - Psychological care of children and adolescents with diabetes.

PMID- 19754629
TI  - Diabetes in adolescence.

PMID- 19754630
TI  - Microvascular and macrovascular complications associated with diabetes in
      children and adolescents.

PMID- 19754631
TI  - Other complications and associated conditions with diabetes in children and
      adolescents.

PMID- 19754632
TI  - A bibliometric study of scientific literature on obesity research in PubMed (1988
      2007).
AB  - This article describes a bibliometric review of the publications on obesity
      research in PubMed over the last 20 years. We used Medline via the PubMed online
      service of the US National Library of Medicine from 1988 to 2007. The search
      strategy was: ([obesity] in MesH). A total of 58,325 references were retrieved,
      25.5% in 1988-1997, and 74.5% in 1998-2007. The growth in the number of
      publications showed an exponential increase. The references were published in
      3613 different journals, with 20 journals contributing 25% of obesity literature.
      The two journals contributing most were the International Journal of Obesity
      (5.1%), Obesity-Obesity Research (2.9%). North America and Europe were the most
      productive world areas with 44.1% and 37.9% of the literature, respectively. The
      US was the predominant country in number of publications, followed by the United
      Kingdom, Japan and Italy. The ranking of production changed when the number of
      publications was normalized by population, gross domestic product and obesity
      prevalence by countries. The great increase of publications on obesity during the
      period 1988-2007 was particularly evident in the second decade of the period
      which is concordant with the worldwide obesity epidemic. USA and Europe were
      leaders in the production of scientific articles on obesity.

PMID- 19754633
TI  - Effectiveness of web-based interventions in achieving weight loss and weight loss
      maintenance in overweight and obese adults: a systematic review with meta
      analysis.
AB  - The objectives of this systematic review are to evaluate the effectiveness of web
      based interventions on weight loss and maintenance and identify which components
      of web-based interventions are associated with greater weight change and low
      attrition rates. A literature search from 1995 to April 2008 was conducted.
      Studies were eligible for inclusion if: participants were aged >or=18 years with
      a body mass index >or=25, at least one study arm involved a web-based
      intervention with the primary aim of weight loss or maintenance, and reported
      weight-related outcomes. Eighteen studies met the inclusion criteria. Thirteen
      studies aimed to achieve weight loss, and five focused on weight maintenance.
      Heterogeneity was evident among the studies with seven research questions
      examined across interventions of varying intensity. Seven studies were assessed
      for effectiveness based on percentage weight change, with four studies deemed
      effective. Although the four meta-analyses suggest meaningful weight change, it
      is not possible to determine the effectiveness of web-based interventions in
      achieving weight loss or maintenance due to heterogeneity of designs and thus the
      small number of comparable studies. Higher usage of website features may be
      associated with positive weight change, but we do not know what features improve
      this effect or reduce attrition.

PMID- 19754634
TI  - Systematic review of long-term lifestyle interventions to prevent weight gain and
      morbidity in adults.
AB  - The aim of this article is to determine the effectiveness of long-term lifestyle
      interventions for the prevention of weight gain and morbidity in adults.
      Prevention of weight gain is important in adults who are of normal weight,
      overweight and obese. A systematic review of controlled trials of lifestyle
      interventions in adults with a body mass index of less than 35 kg m(-2) with at
      least 2 years of follow-up was carried out. Eleven of 39 comparisons produced
      significant improvement in weight between groups at 2 years or longer with mean
      difference weight change ranging from -0.5 to -11.5 kg. Effective interventions
      included a 600 kcal/day deficit diet deficit/low-fat diet (with and without meal
      replacements), low-calorie diet, Weight Watchers diet, low-fat non-reducing diet,
      diet with behaviour therapy, diet with exercise, diet with exercise and behaviour
      therapy. Adding meal replacements to a low-fat diet (with and without exercise
      and behaviour therapy) produced significant improvement in weight. Head-to-head
      interventions failed to show significant effect on weight with the exception of a
      Mediterranean diet with behaviour therapy compared with low-fat diet. Diet with
      exercise and/or behaviour therapy demonstrated significant reduction in
      hypertension and improvement in risk of metabolic syndrome and diabetes compared
      with no treatment control. Lifestyle interventions demonstrated significant
      improvement in weight, reduction in hypertension and reduction in risk of type 2
      diabetes and the metabolic syndrome.

PMID- 19754635
TI  - Arbuscular mycorrhizal colonization reduces arsenate uptake in barley via
      downregulation of transporters in the direct epidermal phosphate uptake pathway.
AB  - *Here, we used barley (Hordeum vulgare) grown in normal and compartmented pots to
      investigate sensitivity to arsenic (As) in the absence of a positive growth
      response to arbuscular mycorrhizas (AM). *We tested the hypothesis that upon
      inoculation with AM fungi downregulation of HvPht1;1 and HvPht1;2 genes (encoding
      high-affinity inorganic orthophosphate (P(i))-uptake systems in a direct pathway
      via root epidermis and root hairs) and upregulation of the AM-induced HvPht1;8
      (encoding the P(i)-uptake system responsible for transfer of P(i) from the
      symbiotic interface to cortical cells) play a role in decreased As uptake and
      hence reduced As sensitivity in AM plants. *Barley did not respond, or responded
      negatively to colonization by Glomus intraradices in terms of growth. In terms of
      specific phosphorus (P) uptake (P uptake per g of root) barley was nonresponsive.
      There was a significant interaction between As treatment and colonization,
      resulting in a lower As concentration and uptake in AM compared with
      nonmycorrhizal (NM) plants. *The decreased uptake of As and higher P : As molar
      ratios in the AM barley can be explained by the operation of the AM pathway as
      indicated by induction of HvPht1;8 and by down-regulation of HvPht1;1 and
      HvPht1;2.

PMID- 19754636
TI  - Chemical interactions in diatoms: role of polyunsaturated aldehydes and
      precursors.
AB  - Chemicals produced by aquatic organisms, and especially micro-organisms, have
      received increasing attention in the last decade for their role in shaping
      interactions and communities. Several cases emphasize the fact that chemical
      signals or defence may modulate interspecific interactions. Notably, it has been
      shown that diatoms, unicellular algae and key primary producers in aquatic
      ecosystems produce a wide range of bioactive metabolites. Among these compounds,
      polyunsaturated short-chain aldehydes in vitro strongly impair the reproduction
      of various potential grazers. In the field, the relationship between aldehyde
      production and reproductive failure in copepods remains unclear. Recent studies
      have suggested that these putative defence compounds may also be involved in
      intercellular communication and in interactions with competitors. Potential
      effects of the aldehyde precursors on various organisms have also been described.
      This review presents an overview of various results obtained in the last decade
      that could help us to understand the role of polyunsaturated aldehydes and their
      precursors in the ecology of diatoms. It is focused on the dichotomy between
      freshwater and marine environments. Indeed, most of the results on anti
      proliferative aldehydes concern marine planktonic diatoms, whereas they are also
      known to be produced by benthic and freshwater species.

PMID- 19754637
TI  - A relationship between galactic cosmic radiation and tree rings.
AB  - Here, we investigated the interannual variation in the growth rings formed by
      Sitka spruce (Picea sitchensis) trees in northern Britain (55 degrees N, 3
      degrees W) over the period 1961-2005 in an attempt to disentangle the influence
      of atmospheric variables acting at different times of year. Annual growth rings,
      measured along the north radius of freshly cut (frozen) tree discs and
      climatological data recorded at an adjacent site were used in the study.
      Correlations were based on Pearson product-moment correlation coefficients
      between the annual growth anomaly and these climatic and atmospheric factors.
      Rather weak correlations between these variables and growth were found. However,
      there was a consistent and statistically significant relationship between growth
      of the trees and the flux density of galactic cosmic radiation. Moreover, there
      was an underlying periodicity in growth, with four minima since 1961, resembling
      the period cycle of galactic cosmic radiation. * We discuss the hypotheses that
      might explain this correlation: the tendency of galactic cosmic radiation to
      produce cloud condensation nuclei, which in turn increases the diffuse component
      of solar radiation, and thus increases the photosynthesis of the forest canopy.

PMID- 19754638
TI  - Stem-mediated hydraulic redistribution in large roots on opposing sides of a
      Douglas-fir tree following localized irrigation.
AB  - *Increasing evidence about hydraulic redistribution and its ecological
      consequences is emerging. Hydraulic redistribution results from an interplay
      between competing plant and soil water potential gradients. In this work, stem
      mediated hydraulic redistribution was studied in a 53-year-old Douglas-fir tree
      during a period of drought. *Sap flux density measurements using the heat field
      deformation method were performed at four locations: in two large opposing roots
      and on two sides of the tree stem. Hydraulic redistribution was induced by
      localized irrigation on one of the measured roots, creating heterogeneous soil
      water conditions. *Stem-mediated hydraulic redistribution was detected during
      night-time conditions when water was redistributed from the wet side of the tree
      to the nonirrigated dry side. In addition to stem-mediated hydraulic
      redistribution, bidirectional flow in the dry root was observed, indicating
      radial sectoring in the xylem. *It was observed that, through stem-mediated
      hydraulic redistribution, Douglas-fir was unable to increase its transpiration
      despite the fact that sufficient water was available to one part of the root
      system. This resulted from the strong water potential gradient created by the dry
      soil in contact with the nonirrigated part of the root system. A mechanism of
      stem-mediated hydraulic redistribution is proposed and its possible implications
      are discussed.

PMID- 19754639
TI  - Natural modifiers of seed longevity in the Arabidopsis mutants abscisic acid
      insensitive3-5 (abi3-5) and leafy cotyledon1-3 (lec1-3).
AB  - *Seed longevity is an important trait in many crops and is essential for the
      success of most land plant species. Current knowledge of its molecular regulation
      is limited. The Arabidopsis mutants abscisic acid insensitive3-5 (abi3-5) and
      leafy cotyledon1-3 (lec1-3) have impaired seed maturation and quickly lose seed
      viability. abi3-5 and lec1-3 were used as sensitized genetic backgrounds for the
      study of seed longevity. *We exploited the natural variation of Arabidopsis to
      create introgression lines from the Seis am Schlern and Shahdara accessions in,
      respectively, the abi3-5 and lec1-3 backgrounds. These lines carry natural
      modifiers of the abi3 and lec1 phenotypes. Longevity tests and a proteomic
      analysis were conducted to describe the seed physiology of each line. *The
      modifier lines showed improved seed longevity. The Shahdara modifiers can
      partially re-establish the seed developmental programs controlled by LEC1 and
      restore the accumulation of seed storage proteins that are reduced in abi3-5 and
      lec1-3. *The isolation and characterization of natural modifiers of the seed
      maturation mutants abi3-5 and lec1-3, and the analysis of their seed proteomes,
      advance our current understanding of seed longevity.

PMID- 19754640
TI  - Differential allocation of carbon in mosses and grasses governs ecosystem
      sequestration: a 13C tracer study in the high Arctic.
AB  - *This study investigates the influence of vegetation composition on carbon (C)
      sequestration in a moss-dominated ecosystem in the Arctic. *A (13)C labelling
      study in an arctic wet meadow was used to trace assimilate into C pools of
      differing recalcitrance within grasses and mosses and to determine the retention
      of C by these plant groups. *Moss retained 70% of assimilated (13)C over the
      month following labelling, which represented half the growing season. By
      contrast, the vascular plants, comprising mostly grasses, retained only 40%. The
      mechanism underlying this was that moss allocated 80% of the (13)C to
      recalcitrant C pools, a much higher proportion than in grasses (56%). *This
      method enabled elucidation of a plant trait that will influence decomposition and
      hence persistence of assimilated C in the ecosystem. We predict that moss
      dominated vegetation will retain sequestered C more strongly than a grass
      dominated community. Given the strong environmental drivers that are causing a
      shift from moss to grass dominance, this is likely to result in a reduction in
      future ecosystem C sink strength.

PMID- 19754641
TI  - Abstracts of the ISSWSH (International Society for the Study of Women's Sexual
      Health) 2009 Annual Meeting. February 12-15, 2009. Florence, Italy.

PMID- 19754642
TI  - Clinical success of zirconia in dental applications.
AB  - The application of ceramic materials for the fabrication of dental restorations
      is a focus of interest in esthetic dentistry. The ceramic materials of choice are
      glass ceramics, spinel, alumina, and zirconia. Zirconia was introduced into
      dentistry in the 1990s because of its good mechanical and chemical properties and
      is currently being used as a material for frameworks, dowels, implants,
      abutments, and orthodontic brackets. Many in vitro studies about zirconia use
      have been published, but clinical long-term studies are very important. This
      article presents data regarding the incidence of clinical success and
      complications of zirconia in these dental applications. Clinical studies
      published to date seem to indicate that zirconia is well tolerated and
      sufficiently resistant.

PMID- 19754643
TI  - Alveolar distraction osteogenesis: revive and restore the native bone.
AB  - In prosthodontics, knife-edge bony alveolar ridges can cause a problem in their
      rehabilitation. The distraction osteogenesis process raises the medullary
      component of the alveolus, allowing the labial plate of the existing natural bone
      to be displaced. This process involves mobilization, transport, and fixation of a
      healthy segment of bone adjacent to the deficient site. It entails use of the
      gradual controlled displacement of surgically created fractures, which results in
      simultaneous expansion of soft tissue and bone volume. A mechanical device, the
      alveolar distraction device, is used for this purpose. This modality of treatment
      can be used in implant dentistry cases for rehabilitation of resorbed ridges. The
      objective of this overview is to explain this procedure wherein the alveolar
      housing, including the osseous and soft-tissue components, is enlarged in a
      single, simultaneous process, which makes creation of an appropriate alveolar
      morphology possible.

PMID- 19754644
TI  - Measurement of interfacial porosity at the acrylic resin/denture tooth interface.
AB  - PURPOSE: Small pores of almost uniform shape and size are common in polymeric
      materials; however, significant porosity can weaken a denture base resin and
      promote staining, harboring of organisms such as Candida albicans, and bond
      failures between the artificial tooth and denture base resin. The aim of this
      study was to investigate the porosity at the interface of one artificial tooth
      acrylic resin (Trilux, copolymer of polymethyl methacrylate, ethylene glycol
      dimethacrylate, and color pigments) and three denture base resins: Acron MC
      (microwave-polymerized), Lucitone 550 (heat-polymerized), and QC-20 (heat
      polymerized). MATERIALS AND METHODS: Ten specimens of each denture base resin
      with artificial tooth were processed. After polymerization, specimens were
      polished and observed under a microscope at 80x magnification. The area of each
      pore present between artificial tooth and denture base resin was measured using
      computer software, and the total area of pores per surface was calculated in
      millimeter square. The Kruskal-Wallis test was performed to compare porosity data
      (alpha= 0.05). RESULTS: Porosity analysis revealed the average number of pores
      (n), area range (S, mm(2)), and diameter range (d, mum) for Acron MC (n = 23, S =
      0.001 to 0.0056, d = 35 to 267), Lucitone 550 (n = 13, S = 0.001 to 0.005, d = 35
      to 79), and QC-20 (n = 19, S = 0.001 to 0.014, d = 35 to 133). The analyses
      showed that there were no statistically significant differences among the groups
      (p= 0.7904). CONCLUSIONS: Within the limitations of this in vitro study, it was
      concluded that the denture base resins evaluated did not affect porosity
      formation at the artificial tooth/denture base resin interface.

PMID- 19754645
TI  - Using a motion-capture system to record dynamic articulation for application in
      CAD/CAM software.
AB  - PURPOSE: One of the current limitations of computer software programs for the
      virtual articulation of the opposing teeth is the static nature of the
      intercuspal position. Currently, software programs cannot identify eccentric
      occlusal contacts during masticatory cyclic movements of the mandible. MATERIALS
      AND METHODS: Chewing trajectories with six degrees of freedom (DOF) were recorded
      and imposed on a computer model of one subject's maxillary and mandibular teeth.
      The computer model was generated from a set of high-resolution micro-CT images.
      To obtain natural chewing trajectories with six DOF, an optoelectronic motion
      capturing system (VICON MX) was used. For this purpose, a special mandibular
      motion-tracking appliance was developed for this subject. RESULTS: Mandibular
      movements while chewing elastic and plastic food samples were recorded and
      reproduced with the computer model. Examples of mandibular movements at intraoral
      points are presented for elastic and plastic food samples. The potential of such
      a kinematic computer model to analyze the dynamic nature of an occlusion was
      demonstrated by investigating the interaction of the second molars and the
      direction of the biting force during a chewing cycle. CONCLUSIONS: The article
      described a methodology that measured mandibular movements during mastication for
      one subject. This produced kinematic input to 3D computer modeling for the
      production of a virtual dynamic articulation that is suitable for incorporation
      into dental CAD/CAM software.

PMID- 19754646
TI  - Assessment of an indirect metal ceramic repair system.
AB  - PURPOSE: This study was designed to compare an alternative indirect treatment to
      repair fractured or chipped veneering metal ceramic using recently developed
      ultra-low-fusing ceramics. MATERIALS AND METHODS: One conventional feldspathic
      ceramic, Vita Omega, and three ultra-low-fusing ceramics (ULFC), Finesse, Duceram
      LFC, and Vision-low, were used. Forty ceramic specimens were prepared and divided
      into two groups. Group I (n = 20) was designed for bond strength testing. It
      comprised four subgroups (A, B, C, D): one Ceramic-resin (A) and three Ceramic
      ULFC disc specimens of different diameters (B, C, D). Group II was composed of
      repaired ceramic discs using direct and indirect repair methods for biaxial
      testing. It was comprised of five subgroups: the fractured discs from subgroup A;
      Omega discs (n = 20) formed the repaired specimens of the four remaining
      subgroups: B, C, D, E. Data were presented as means and standard deviation (SD)
      values. One-way analysis of variance (ANOVA) was used for comparison between
      means. Tukey's post hoc test was used for pairwise comparison between the means
      when ANOVA test was significant. The significance level was set at p<or= 0.05.
      RESULTS: Within group I, Omega-Ducera LFC showed the statistically highest mean
      bond strength (25.8 MPa) values, followed by Omega-Finesse (15.8 MPa). No
      statistically significant difference was apparent between Omega-Vision (9.3 MPa)
      and the control Omega-Composite group (7.5 MPa). Regarding group II, the Control
      Omega subgroup showed statistically the highest mean biaxial strength values
      (168.8 MPa). No statistically significant difference was evident between the
      values of Omega-Finesse (78.7 MPa), Omega-Vision (78.4 MPa), and Omega-Composite
      (82.5 MPa). Omega-Ducera LFC subgroup, showed statistically the lowest mean
      values (53 MPa). CONCLUSIONS: Omega-Ducera LFC yielded the statistically highest
      mean bond strength values, and the lowest biaxial strength values. All values
      were within the reported bond strength values for resin repair. All the tested
      groups showed significantly lower values compared to the initial biaxial strength
      mean values of the Omega ceramic; however, two of the tested ULFC (Vision,
      Finesse), recorded means that were statistically equal to the resin-ceramic
      direct subgroup. Duceram LFC showed the lowest values, probably due to its
      totally glass composition, which showed low strength values of the repaired
      specimens. The recorded bond and biaxial values suggest that indirect repair of
      fractured LFC using some ULFC ceramics may offer an alternative solution to the
      traditional direct resin repair method; however, the choice of the used ceramic
      should be one containing some leucite crystals. Further studies are needed to
      investigate the long-term performance of the proposed repair treatment.

PMID- 19754647
TI  - Differential infiltration of CD8+ and NK cells in lip and oral cavity squamous
      cell carcinoma.
AB  - BACKGROUND: CD8+ and natural killer (NK) cells have been considered the most
      effective cells in the combat of cancer, contributing to better prognosis and
      longer survival. METHODS: The aim of this study was to evaluate the population of
      CD8+ and NK cells, by immunohistochemistry, in samples of oral cavity squamous
      cell carcinoma (OCSCC) and lip squamous cell carcinoma (LSCC), leukoplakia,
      actinic cheilitis, and healthy oral mucosa (control). The relationship of CD8+
      and NK cells with survival data, lymph node metastasis, tumor size, and
      proliferative index was also evaluated. RESULTS: The number of peritumoral and
      intratumoral CD8+ and NK cells was significantly higher in LSCC, when compared
      with control, pre-malignant lesions, and OCSCC. A higher proportion of
      peritumoral CD8+ cells demonstrated correlation with a lower neoplastic
      proliferative index. Moreover, patients with OCSCC with a high density of
      peritumoral CD8+ cells showed a tendency towards a longer survival time.
      CONCLUSIONS: The differential CD8+ and NK cells infiltration in oral SCC might
      reflect a distinctive tumor microenvironment with a favorable local cytotoxic
      immune response against neoplastic cells.

PMID- 19754648
TI  - Legal solutions in health reform.

PMID- 19754649
TI  - Project overview and emerging themes.

PMID- 19754650
TI  - Executive authority to reform health: options and limitations.

PMID- 19754651
TI  - The constitutionality of mandates to purchase health insurance.

PMID- 19754652
TI  - Health insurance exchanges: legal issues.

PMID- 19754653
TI  - Tax credits for health insurance.

PMID- 19754654
TI  - The role of ERISA preemption in health reform: opportunities and limits.

PMID- 19754655
TI  - Insurance discrimination on the basis of health status: an overview of
      discrimination practices, federal law, and federal reform options.

PMID- 19754656
TI  - Privacy and health information technology.

PMID- 19754657
TI  - The purchase of insurance across state lines in the individual market.

PMID- 19754658
TI  - Drug eruption induced by IL-6 receptor inhibitor tocilizumab.

PMID- 19754659
TI  - Paediatric psoriasis--narrowband UVB treatment.
AB  - Narrowband UV-B is a safe and efficacious option for the treatment of adult
      psoriasis. However, the use of this therapy has been limited in children due to
      its long-term carcinogenic potential. It has proven to be an adequate alternative
      in patients whose condition is refractory to topical treatment. AIMS: To evaluate
      the efficacy and short-term safety of narrowband UV-B in the treatment of
      paediatric psoriasis, and to compare our results with those obtained in other
      studies on paediatric psoriasis. MATERIALS AND METHODS: Over a period of 2 years
      and 4 months, we administered narrowband UV-B to 20 children diagnosed with
      psoriasis that was refractory to topical therapy. The therapeutic response was
      measured using the Psoriasis Area and Severity Index (PASI). RESULTS: Between
      August 2005 and December 2007, 20 children received narrowband UV-B. Their median
      age was 13 years (range, 5-17 years), and the median initial PASI score was 8.25
      (2.7-22.2). A median of 28 (10-59) sessions was required to achieve clearance,
      reaching almost complete or total remission (median final PASI) in all but two
      patients. Six patients required a new therapeutic course because of relapse, and
      the mean duration of remission was 8 months (4-18). No patients experienced
      severe adverse events during therapy, and only one discontinued treatment, for
      unrelated reasons. DISCUSSION AND CONCLUSION: Narrowband UV-B for the treatment
      of paediatric psoriasis has received little attention in the literature. This
      treatment has been limited in children because of its potential long-term
      carcinogenic effects, and most information has been extrapolated from adults.
      Nevertheless, narrowband UV-B phototherapy is an effective and well-tolerated
      therapeutic alternative in paediatric patients with severe psoriasis.

PMID- 19754660
TI  - HPV detection in 'large-cell acanthomas': a word of caution.

PMID- 19754661
TI  - 5-HTTLPR moderates the effect of relational peer victimization on depressive
      symptoms in adolescent girls.
AB  - BACKGROUND: Relational peer victimization is associated with internalizing
      symptoms. Compared to boys, girls are more likely to be both relationally
      victimized by peers and distressed by the victimization. While previous studies
      have reported that a functional polymorphism in the promoter region of the
      serotonin transporter gene (5-HTTLPR) moderates the effect of stressful life
      events on depressive symptoms, the present study is the first to evaluate the
      interaction of this polymorphism with relational peer victimization to predict
      level of depressive symptoms in young girls. METHODS: Participants were 78 girls
      ages 10 to 14 who had no current or past Axis I disorder. Girls were genotyped
      for 5-HTTLPR; peer victimization was assessed with the Social Experiences
      Questionnaire, and depressive symptoms with the Children's Depression Inventory.
      RESULTS: The 5-HTTLPR polymorphism alone did not predict level of depressive
      symptoms; the interaction of 5-HTTLPR and relational peer victimization, however,
      was a significant predictor of depressive symptoms. Follow-up analyses indicated
      that peer victimization significantly predicted level of depressive symptoms only
      for girls who were homozygous for the short allele, and not for girls homozygous
      for the long allele or who were heterozygous for the short and long alleles.
      CONCLUSIONS: The findings support the diathesis-stress model of depression:
      having two 5-HTTLPR short alleles confers vulnerability to depressive symptoms in
      adolescent girls when they experience relational peer victimization. These
      findings also suggest that relational peer victimization, at least for girls with
      genetic vulnerability, is a significant source of stress and should be recognized
      in the monitoring and prevention of bullying.

PMID- 19754662
TI  - Do family mealtime interactions mediate the association between asthma symptoms
      and separation anxiety?
AB  - BACKGROUND: Respiratory problems have been shown to be associated with the
      development of panic anxiety. Family members play an essential role for children
      to emotionally manage their symptoms. This study aimed to examine the relation
      between severity of respiratory symptoms in children with asthma and separation
      anxiety. Relying on direct observation of family interactions during a mealtime,
      a model is tested whereby family interactions mediate the relation between asthma
      severity and separation anxiety symptoms. METHODS: Sixty-three children (ages 9
      12 years) with persistent asthma were interviewed via the Diagnostic Interview
      Schedule for Children IV; family interactions were assessed via direct
      observation of a mealtime; primary caregivers completed the Childhood Asthma
      Severity Scale; youth pulmonary function was ascertained with pre- and post
      bronchodilator spirometry; adherence to asthma medications was objectively
      tracked for six weeks. RESULTS: Poorer pulmonary function and higher functional
      asthma severity were related to higher numbers of separation anxiety symptoms.
      Controlling for medication adherence, family interaction patterns mediated the
      relationship between poorer pulmonary function and child separation anxiety
      symptoms. CONCLUSIONS: Family mealtime interactions may be a mechanism by which
      respiratory disorders are associated with separation anxiety symptoms in
      children, potentially through increasing the child's capacity to cognitively
      frame asthma symptoms as less threatening, or through increasing the child's
      sense of security within their family relationships.

PMID- 19754663
TI  - Affinity pulldown of gamma-secretase and associated proteins from human and rat
      brain.
AB  - gamma-Secretase is a transmembrane protease complex responsible for the
      processing of a multitude of type 1 transmembrane proteins, including amyloid
      precursor protein (APP) and Notch. A functional complex is dependent on the
      assembly of four proteins: presenilin (PS), nicastrin, Aph-1 and Pen-2. Little is
      known about how the substrates are selected by gamma-secretase, but it has been
      suggested that gamma-secretase associated proteins (GSAPs) could be of
      importance. For instance, it was recently reported from studies in cell lines
      that TMP21, a transmembrane protein involved in trafficking, binds to gamma
      secretase and regulates the processing of APP-derived substrates without
      affecting Notch cleavage. Here, we present an efficient and selective method for
      purification and analysis of gamma-secretase and GSAPs. Microsomal membranes were
      prepared from rat or human brain and incubated with a gamma-secretase inhibitor
      coupled to biotin via a long linker and a S-S bridge. After pulldown using
      streptavidin beads, bound proteins were eluted under reducing conditions and
      digested by trypsin. The tryptic peptides were subjected to LC-MS/MS analysis,
      and proteins were identified by sequence data from MS/MS spectra. All of the
      known gamma-secretase components were identified. Interestingly, TMP21 and the PS
      associated protein syntaxin1 were associated to gamma-secretase in rat brain. We
      suggest that the present method can be used for further studies on the
      composition of the gamma-secretase complex.

PMID- 19754665
TI  - Chromosomal instability correlates with poor outcome in patients with
      myelodysplastic syndromes irrespectively of the cytogenetic risk group.
AB  - Chromosomal instability (CIN), defined by an elevated frequency of the occurrence
      of novel chromosomal aberrations, is strongly implicated in the generation of
      aneuploidy, one of the hallmarks of human cancers. As for aneuploidy itself, the
      role of CIN in the evolution and progression of malignancy is a matter still open
      to debate. We investigated numerical as well as structural CIN in primary CD34
      positive cells by determining the cell-to-cell variability of the chromosome
      content using fluorescence-in situ-hybridization (FISH). Thereby, CIN was
      measured in 65 patients with myelodysplastic syndromes (MDS), acute myeloid
      leukaemia (AML) and control subjects. Among MDS patients, a subgroup with
      elevated levels of CIN was identified. At a median follow-up of 17.2 months, all
      patients within this 'high CIN' subgroup had died or progressed to AML, while 80%
      of MDS patients with normal CIN levels had stable disease (P < 0.001). Notably,
      there was no statistically significant difference between 'normal CIN' and 'high
      CIN' MDS patients regarding established risk factors. Hence, elevated CIN levels
      were associated with poor outcome, and our method provided additional prognostic
      information beyond conventional cytogenetics. Furthermore, in all three MDS
      patients for whom serial measurements were available, development of AML was
      preceded by increasing CIN levels. In conclusion, elevated CIN levels may be
      valuable as an early indicator of poor prognosis in MDS, hence corroborating the
      concept of CIN as a driving force in tumour progression.

PMID- 19754664
TI  - Genetic characterization of breast cancer and implications for clinical
      management.
AB  - Breast cancer is a genetic disease caused by the accumulation of mutations in
      neoplastic cells. In the last few years, high-throughput microarray-based
      molecular analysis has provided increasingly more coherent information about the
      genetic aberrations in breast cancer. New biomarkers and molecular techniques are
      slowly becoming part of the diagnostic and prognostic armamentarium available for
      pathologists and oncologists to tailor the therapy for breast cancer patients. In
      this review, we will focus on the contribution of breast cancer somatic genetics
      to our understanding of breast cancer biology and its impact on breast cancer
      patient management.

PMID- 19754666
TI  - TNF-alpha-mediated signal transduction pathway is a major determinant of
      apoptosis in dilated cardiomyopathy.
AB  - Although J2N-k strain of cardiomyopathic hamsters is an excellent model of
      dilated cardiomyopathy, the presence and mechanisms of apoptosis in the hearts of
      these genetically modified animals have not been investigated. This study
      examined the hypothesis that cardiac dysfunction and apoptosis in the
      cardiomyopathic hamsters were associated with tumour necrosis factor-alpha (TNF
      alpha)-mediated signalling pathway involving the activation of some pro-apoptotic
      proteins and/or deactivation of some antiapoptotic proteins. Echocardiographic
      assessment of 31-week-old hamsters indicated an increase in the internal
      dimension of the left ventricle as well as decreases in the ejection fraction,
      fractional shortening and cardiac output without any evidence of cardiac
      hypertrophy. Increased level of TNF-alpha and apoptosis in cardiomyopathic hearts
      were accompanied by increased protein content for protein kinase C (PKC) -alpha
      and -epsilon isozymes as well as caspases 3 and 9. Phosphorylated protein content
      for p38 MAPK and NF kappaB was increased whereas that for Erk1/2, BAD and Bcl-2
      was decreased in cardiomyopathic hearts. These results support the view that TNF
      alpha and PKC isozymes may promote apoptosis due to the activation of p38 MAPK
      and deactivation of Erk1/2 pathways, and these changes may contribute toward the
      development of cardiac dysfunction in dilated cardiomyopathy.

PMID- 19754667
TI  - Monocyte transplantation for neural and cardiovascular ischemia repair.
AB  - Neovascularization is an integral process of inflammatory reactions and
      subsequent repair cascades in tissue injury. Monocytes/macrophages play a key
      role in the inflammatory process including angiogenesis as well as the defence
      mechanisms by exerting microbicidal and immunomodulatory activity. Current
      studies have demonstrated that recruited monocytes/macrophages aid in regulating
      angiogenesis in ischemic tissue, tumours and chronic inflammation. In terms of
      neovascularization followed by tissue regeneration, monocytes/macrophages should
      be highly attractive for cell-based therapy compared to any other stem cells due
      to their considerable advantages: non-oncogenic, non-teratogenic, multiple
      secretary functions including pro-angiogenic and growth factors, straightforward
      cell harvesting procedure and non-existent ethical controversy. In addition to
      adult origins such as bone marrow or peripheral blood, umbilical cord blood (UCB)
      can be a potential source for autologous or allogeneic monocytes/macrophages.
      Especially, UCB monocytes should be considered as the first candidate owing to
      their feasibility, low immune rejection and multiple characteristic advantages
      such as their anti-inflammatory properties by virtue of their unique immune and
      inflammatory immaturity, and their pro-angiogenic ability. In this review, we
      present general characteristics and potential of monocytes/macrophages for cell
      based therapy, especially focusing on neovascularization and UCB-derived
      monocytes.

PMID- 19754669
TI  - Helicobacter pylori urease activates blood platelets through a lipoxygenase
      mediated pathway.
AB  - The bacterium Helicobacter pylori causes peptic ulcers and gastric cancer in
      human beings by mechanisms yet not fully understood. H. pylori produces urease
      which neutralizes the acidic medium permitting its survival in the stomach. We
      have previously shown that ureases from jackbean, soybean or Bacillus pasteurii
      induce blood platelet aggregation independently of their enzyme activity by a
      pathway requiring platelet secretion, activation of calcium channels and
      lipoxygenase-derived eicosanoids. We investigated whether H. pylori urease
      displays platelet-activating properties and defined biochemical pathways involved
      in this phenomenon. For that the effects of purified recombinant H. pylori urease
      (HPU) added to rabbit platelets were assessed turbidimetrically. ATP secretion
      and production of lipoxygenase metabolites by activated platelets were measured.
      Fluorescein-labelled HPU bound to platelets but not to erythrocytes. HPU induced
      aggregation of rabbit platelets (ED(50) 0.28 microM) accompanied by ATP
      secretion. No correlation was found between platelet activation and ureolytic
      activity of HPU. Platelet aggregation was blocked by esculetin (12-lipoxygenase
      inhibitor) and enhanced approximately 3-fold by indomethacin (cyclooxygenase
      inhibitor). A metabolite of 12-lipoxygenase was produced by platelets exposed to
      HPU. Platelet responses to HPU did not involve platelet-activating factor, but
      required activation of verapamil-inhibitable calcium channels. Our data show that
      purified H. pylori urease activates blood platelets at submicromolar
      concentrations. This property seems to be common to ureases regardless of their
      source (plant or bacteria) or quaternary structure (single, di- or tri-chain
      proteins). These properties of HPU could play an important role in pathogenesis
      of gastrointestinal and associated cardiovascular diseases caused by H. pylori.

PMID- 19754668
TI  - Imatinib inhibits vascular smooth muscle proteoglycan synthesis and reduces LDL
      binding in vitro and aortic lipid deposition in vivo.
AB  - The 'response to retention' hypothesis of atherogenesis proposes that
      proteoglycans bind and retain low-density lipoproteins (LDL) in the vessel wall.
      Platelet-derived growth factor (PDGF) is strongly implicated in atherosclerosis
      and stimulates proteoglycan synthesis. Here we investigated the action of the
      PDGF receptor inhibitor imatinib on PDGF-mediated proteoglycan biosynthesis in
      vitro, lipid deposition in the aortic wall in vivo and the carotid artery ex
      vivo. In human vSMCs, imatinib inhibited PDGF mediated (35)S-SO(4) incorporation
      into proteoglycans by 31% (P < 0.01) and inhibited PDGF-mediated size increases
      in both chemically cleaved and xyloside associated glycosaminoglycan (GAG) chains
      by 19%, P < 0.05 and 27%, P < 0.05, respectively. Imatinib decreased PDGF
      stimulation of the 6:4 position sulphation ratio of disaccharides. The half
      maximal saturation value for LDL binding for proteoglycans from PDGF stimulated
      cells in the presence of imatinib was approximately 2.5-fold higher than for PDGF
      treatment alone. In high fat fed ApoE(-/-) mice, imatinib reduced total lipid
      staining area by approximately 31% (P < 0.05). Carotid artery lipid accumulation
      in imatinib treated mice was also reduced. Furthermore, we demonstrate that
      imatinib inhibits phosphorylation of tyrosine 857, the autophosphorylation site
      of the PDGF receptor, in vSMCs. Thus imatinib inhibits GAG synthesis on vascular
      proteoglycans and reduces LDL binding in vitro and in vivo and this effect is
      mediated via the PDGF receptor. These findings validate a novel mechanism to
      prevent cardiac disease.

PMID- 19754670
TI  - Role of AKT-glycogen synthase kinase axis in monocyte activation in human beings
      with and without type 2 diabetes.
AB  - Monocyte activation by chemokines is a vital trigger for initiation of
      atherosclerotic process. Circulating levels of platelet activating factor (PAF),
      a recognized chemokine, is known to be increased in type 2 diabetes that is
      linked to accelerated atherosclerosis. To explore the molecular basis we examined
      the signalling pathways involved in PAF induced monocyte activation. PAF
      increased migration in monocytes obtained from THP-1 cells, nondiabetic and
      diabetic subjects. This effect was blocked by AKT inhibition. It did so by
      phosphorylation of glycogen synthase kinase (GSK)-3betaS(9), which was completely
      blocked by AKT inhibition. Additionally, PAF induced GSK-3beta phosphorylation
      was linked to Rac-1 activation and Rho-A inactivation leading to migration.
      Paradoxically, inhibition of GSK-3beta phosphorylation also augmented monocyte
      migration in THP-1, ND and diabetic monocytes through phosphorylation of AKT and
      activation of Rho-A that was independent of GSK. This was validated when (i)
      overexpression of dominant negative mutants of Rho-A reversed GSK inhibitor
      induced monocyte migration and (ii) AKT inhibition blocked GSK inhibitor induced
      Rho-A activity. Constitutively active ARAP3 (Rho-GAP) appears to have a
      regulatory role in monocyte activity during GSK inhibition. Finally, inhibition
      of monocyte GSK-3beta activity (by inhibitors and genetic manipulation) led to
      enhanced migration in diabetes compared to persons without diabetes. We conclude
      that diabetic monocytes show increased migratory capacity in response to GSK
      3beta inhibition. GSK inhibitors developed to treat the metabolic complications
      of diabetes should therefore be used with caution.

PMID- 19754671
TI  - Resistin competes with lipopolysaccharide for binding to toll-like receptor 4.
AB  - Toll-like receptors (TLRs) are a family of cellular structures activated by
      recognition of pathogen associated molecular sequences. The activation of TLRs
      triggers a variety of intracellular mechanisms aiming to protect the host from
      the invading microorganisms. Lipopolysaccharide (LPS) is the main ligand for
      TLR4. Here we show that resistin, a cystein-rich protein believed to regulate
      carbohydrate metabolism, competes with LPS for binding to TLR4. Binding of
      recombinant resistin to human myeloid and epithelial cells was assessed by flow
      cytometry and its co-precipitation with TLR4 was demonstrated. Antibodies against
      TLR4 abolished resistin binding to human leucocytes and cytokine production by
      peripheral blood mononuclear cells in response to resistin stimulation. In
      contrast, isotype-matched murine IgG or TLR2 antibodies were unable to prevent
      binding of resistin to the cells. Similarly, TLR4-dependent pattern of resistin
      binding was observed in epithelial cell line HEK293 (human epithelial kidney
      cell), where TLR4 transfected, but not myeloid differentiation factor 2/CD14
      transfected, TLR2 transfected or HEKnull cells, responded functionally to
      resistin stimulation. Intracellular signalling of resistin was assessed using
      inhibitors of transcription factors mitogen activated protein kinases, nuclear
      factor-kappaB, phosphoinositide 3-kinase and siRNA targeting TLR4 and human
      myeloid differentiation factor 88. Results demonstrate that TLR4 serves as a
      receptor for the pro-inflammatory effects of resistin in human cells. This may
      partly explain the multifunctional role of resistin in chronic inflammation,
      atherosclerosis and insulin resistance.

PMID- 19754672
TI  - Acceleration of muscle regeneration by local injection of muscle-specific
      microRNAs in rat skeletal muscle injury model.
AB  - MicroRNA (miRNA)s are a class of non-coding RNAs that regulate gene expression
      post-transcriptionally. Muscle-specific miRNA, miRNA (miR)-1, miR-133 and miR-206
      play a crucial role in the regulation of muscle development and homeostasis.
      Muscle injuries are a common musculoskeletal disorder, and the most effective
      treatment has not been established yet. The purpose of this study was to
      demonstrate that a local injection of double-stranded (ds) miR-1, miR-133 and 206
      can accelerate muscle regeneration in a rat skeletal muscle injury model. After
      the laceration of the rat tibialis anterior muscle, ds miR-1, 133 and 206 mixture
      mediated atelocollagen was injected into the injured site. The control group was
      injected with control siRNA. At 1 week after injury, an injection of miRNAs could
      enhance muscle regeneration morphologically and physiologically, and prevent
      fibrosis effectively compared to the control siRNA. Administration of exogenous
      miR-1, 133 and 206 can induce expression of myogenic markers, MyoD1, myogenin and
      Pax7 in mRNA and expression in the protein level at 3 and 7 days after injury.
      The combination of miR-1, 133 and 206 can promote myotube differentiation, and
      the expression of MyoD1, myogenin and Pax7 were up-regulated in C2C12 cells in
      vitro. Local injection of miR-1, 133 and 206 could be a novel therapeutic
      strategy in the treatment of skeletal muscle injury.

PMID- 19754675
TI  - Endovascular stent: grafting in penetrating atherosclerotic ulcer of the thoracic
      aorta.
AB  - The aim of our study is the presentation of some interesting images of a case
      with symptomatic penetrating atherosclerotic ulcer (PAU) of the thoracic aorta
      and its endovascular treatment. Penetrating atherosclerotic ulcer is an
      ulcerating atherosclerotic lesion that penetrates the elastic lamina and is
      correlated with intramural hematoma (IMH) formation into the media layer of the
      aortic wall. PAU is more common in the elderly with severe atherosclerosis,
      hypertension, and hyperlipidemia. Transesophageal echocardiography, computed
      tomography, and magnetic resonance imaging are the common diagnostic tools.
      Surgical treatment may become necessary in cases involving the ascending aorta or
      in cases of intramural haematoma formation. In the era of minimally invasive
      surgery stent-grafting is indicated mainly in the elderly patients in presence of
      serious co-morbidities.

PMID- 19754673
TI  - Chemical and molecular mechanisms of antioxidants: experimental approaches and
      model systems.
AB  - Free radicals derived from oxygen, nitrogen and sulphur molecules in the
      biological system are highly active to react with other molecules due to their
      unpaired electrons. These radicals are important part of groups of molecules
      called reactive oxygen/nitrogen species (ROS/RNS), which are produced during
      cellular metabolism and functional activities and have important roles in cell
      signalling, apoptosis, gene expression and ion transportation. However, excessive
      ROS attack bases in nucleic acids, amino acid side chains in proteins and double
      bonds in unsaturated fatty acids, and cause oxidative stress, which can damage
      DNA, RNA, proteins and lipids resulting in an increased risk for cardiovascular
      disease, cancer, autism and other diseases. Intracellular antioxidant enzymes and
      intake of dietary antioxidants may help to maintain an adequate antioxidant
      status in the body. In the past decades, new molecular techniques, cell cultures
      and animal models have been established to study the effects and mechanisms of
      antioxidants on ROS. The chemical and molecular approaches have been used to
      study the mechanism and kinetics of antioxidants and to identify new potent
      antioxidants. Antioxidants can decrease the oxidative damage directly via
      reacting with free radicals or indirectly by inhibiting the activity or
      expression of free radical generating enzymes or enhancing the activity or
      expression of intracellular antioxidant enzymes. The new chemical and cell-free
      biological system has been applied in dissecting the molecular action of
      antioxidants. This review focuses on the research approaches that have been used
      to study oxidative stress and antioxidants in lipid peroxidation, DNA damage,
      protein modification as well as enzyme activity, with emphasis on the chemical
      and cell-free biological system.

PMID- 19754676
TI  - Comparison of three different surgical methods in aortic root aneurysms: long
      term results.
AB  - BACKGROUND: Degenerative ascending aortic aneurysms frequently present with
      aortic valve pathology. If only the noncoronary sinus of Valsalva is dilated,
      replacement of the noncoronary sinus by tailoring the supracoronary graft with or
      without aortic valve replacement (AVR) can be a simple operation strategy. We
      sought to describe our experiences in this kind of operation, and compare them
      with a relatively homogeneous group of patients who underwent the classical
      Bentall operation. METHODS: Between January 1997 and June 2007, 99 patients who
      had dilated ascending aortas with root dilatation and aortic valve pathology
      underwent operation. Patients were divided into three groups according to the
      surgical procedure. Classical Bentall operation was applied in 54 patients with
      dilated sinuses (Group 1). The other patients with dilated noncoronary sinus
      underwent either ascending aortic replacement with noncoronary sinus replacement
      (NSR, n = 27) (Group 2), or separate AVR and ascending aortic replacement with
      NSR (AVR + NSR, n = 18) (Group 3). RESULTS: There were significant reduction of
      aortic root in Group 2 (Z =-4.560, p < 0.001), and Group 3 (Z =-3.758, p <
      0.001). Degree of aortic regurgitation was decreased from 1.56 +/- 0.5 to 0.67 +/
      0.5 postoperatively in Group 2 (Z =-3.874, p < 0.001). Hospital mortality was
      six (6.1%) (three in Group 1; three in Group 2). Late mortality rate was 6.1%
      (three in Group 1, three in Group 2). The type of operation was not found to be
      an independent predictor of overall mortality. No patients in the NSR and AVR-NSR
      groups had aortic root aneurysm, and there were no reoperations or verified
      deaths caused by aortic root aneurysm in these patients. CONCLUSIONS: Noncoronary
      cusp replacement for aortic root remodeling in patients with ascending aortic
      aneurysm is a technically simple and durable operation. Short- and mid-term
      results of this method were favorable compared to the Bentall procedure.

PMID- 19754677
TI  - Free-floating tumor thrombus in the left atrium associated with non-small cell
      lung cancer.
AB  - A free-floating tumor thrombus in the left atrium is an unusual metastasis of non
      small cell lung cancer. Surgical resection of free-floating tumor thrombus prior
      to adjuvant therapy relieves cardiac symptoms such as exertional dyspnea, and
      prevents life-threatening complications including systemic embolization, mitral
      obstruction, or sudden death.

PMID- 19754678
TI  - Total arch replacement with stented elephant trunk technique: a proposed
      treatment for complicated Stanford type B aortic dissection.
AB  - OBJECTIVES: The treatment of Stanford type B aortic dissections involving the
      arch or associated with proximal aortic aneurysms remains a surgical challenge.
      We report our results with total arch replacement with the stented elephant trunk
      (SET) procedure for these complicated Stanford type B aortic dissections.
      METHODS: Between December 2003 and June 2008, 31 patients were admitted for
      complicated type B dissection (12 acute, 19 chronic). The mean age at operation
      was 44.3 +/- 10.6 years (range: 22-68 years). The surgeries were performed by
      using total arch replacement combined with SET implantation. Enhanced computed
      tomography (CT) was performed before discharge as well as 3 months and annually
      to evaluate the condition of the graft and the residual false lumen. RESULTS: The
      procedure was successful in all but two patients; two patients died of multiple
      organ failure following surgery. No paraplegia was observed after surgery. Follow
      up was completed in 27 of 29 patients and the mean follow-up period was 18.4 +/-
      12.3 months (range: 6-54 months). During follow-up CT scans, thrombus formation
      was observed in the descending aortic false lumen excluded by the stented graft
      in most patients. One patient died during follow-up while two patients with
      Marfan syndrome underwent successful operations for replacement of the remaining
      descending and abdominal aorta. CONCLUSION: Total arch replacement with the SET
      procedure has emerged as a viable option for complicated type B dissections and
      is associated with low morbidity and mortality. At mid-term follow-up, most
      patients have either thrombosed or have had no further increase in the false
      lumen of the descending aorta.

PMID- 19754679
TI  - Aprotinin attenuates genomic expression variability following cardiac surgery.
AB  - BACKGROUND: Aprotinin was the subject of recent controversy regarding adverse
      clinical outcomes following cardiac surgery. We compared the role of Aprotinin
      and epsilon-aminocaproic acid on clinical outcomes and the attenuation of the
      postcardiopulmonary bypass (CPB) response at the genomic expression and cytokine
      (protein) level. METHODS: Thirty-nine low-risk patients undergoing coronary
      revascularization (CABG) and/or valve procedures using cardiopulmonary CPB were
      enrolled into a prospective cohort study. Aprotinin or epsilon-aminocaproic acid
      was administered to patients. Gene expression was assessed from whole blood mRNA
      samples collected preoperatively (PRE) and 6 hours (6H) postoperatively.
      Validation of gene expression was performed with SYBR Green real-time polymerase
      chain reaction. Cytokine values were quantified from serum preoperatively and
      postoperatively at 6 H and 4 days and analyzed in a blinded fashion. RESULTS: No
      difference was detected in baseline characteristics. Inflammatory markers
      measured did not reveal significant difference between patients receiving
      Aprotinin (APR) and those receiving epsilon-aminocaproic acid (Amicar).
      Intraoperative parameters and postoperative outcomes were not significantly
      different. Compared with PRE samples, 6H samples had 264 upregulated and 548
      downregulated genes uniquely in the APR group compared to 4826 upregulated and
      1114 downregulated genes uniquely in the Amicar group (p < 0.001). Compared to
      patients in the Amicar group, APR patients had significantly different gene
      expression pathways involving NF-kappabeta regulation, programmed cell death and
      cell-cell adhesion. None of the patients developed postoperative stroke,
      myocardial infarction, or systemic infections. CONCLUSIONS: Aprotinin leads to
      significantly less genomic expression variability following CPB compared to
      Amicar and has a differential effect on specific genomic pathways.

PMID- 19754680
TI  - Bridge to heart transplantation with left ventricular assist device versus
      inotropic agents in status 1 patients.
AB  - OBJECTIVE: Left ventricular assist devices (LVADs) are commonly used for
      critically ill patients awaiting heart transplantation, although their effect on
      long-term outcomes, relative to inotropic support alone, is still debated.
      METHOD: Data from Status 1 patients who underwent heart transplantation at our
      institution between 1990 and 2005 were reviewed (n = 180). They were divided into
      two groups: those who underwent LVAD implantation as a bridge to transplant (n =
      31) and those treated with inotropic agents without the support of LVAD (n =
      149). They were compared in terms of demographics and clinical outcome. RESULTS:
      Both groups were similar in terms of patient and donor demographics. Relative to
      the inotrope group, the LVAD group did have a longer ischemic time (p = 0.032), a
      greater incidence of pretransplant transfusion (p < 0.00001), and a greater
      maximum level of pretransplant panel reactive antibodies (p < 0.001). Creatinine
      at listing significantly improved in LVAD patients awaiting transplantation (p <
      0.0001). Comparisons of 5-year survival in addition to freedom from
      posttransplant infection, malignancy, revascularization, and acute rejection did
      not show significant difference between the two groups. The LVAD group did
      benefit from increased freedom from chronic rejection compared to the inotrope
      group (p = 0.049). Stepwise Cox Regression did not identify any independent
      factors affecting patient survival during the first 5 years after transplant.
      CONCLUSIONS: Status 1 patients successfully bridged to heart transplantation with
      LVADs had similar long-term clinical outcomes compared to those treated with
      inotropic agents.

PMID- 19754681
TI  - Survival and breeding of polar bears in the southern Beaufort Sea in relation to
      sea ice.
AB  - 1. Observed and predicted declines in Arctic sea ice have raised concerns about
      marine mammals. In May 2008, the US Fish and Wildlife Service listed polar bears
      (Ursus maritimus) - one of the most ice-dependent marine mammals - as threatened
      under the US Endangered Species Act. 2. We evaluated the effects of sea ice
      conditions on vital rates (survival and breeding probabilities) for polar bears
      in the southern Beaufort Sea. Although sea ice declines in this and other regions
      of the polar basin have been among the greatest in the Arctic, to date population
      level effects of sea ice loss on polar bears have only been identified in western
      Hudson Bay, near the southern limit of the species' range. 3. We estimated vital
      rates using multistate capture-recapture models that classified individuals by
      sex, age and reproductive category. We used multimodel inference to evaluate a
      range of statistical models, all of which were structurally based on the polar
      bear life cycle. We estimated parameters by model averaging, and developed a
      parametric bootstrap procedure to quantify parameter uncertainty. 4. In the most
      supported models, polar bear survival declined with an increasing number of days
      per year that waters over the continental shelf were ice free. In 2001-2003, the
      ice-free period was relatively short (mean 101 days) and adult female survival
      was high (0.96-0.99, depending on reproductive state). In 2004 and 2005, the ice
      free period was longer (mean 135 days) and adult female survival was low (0.73
      0.79, depending on reproductive state). Breeding rates and cub litter survival
      also declined with increasing duration of the ice-free period. Confidence
      intervals on vital rate estimates were wide. 5. The effects of sea ice loss on
      polar bears in the southern Beaufort Sea may apply to polar bear populations in
      other portions of the polar basin that have similar sea ice dynamics and have
      experienced similar, or more severe, sea ice declines. Our findings therefore are
      relevant to the extinction risk facing approximately one-third of the world's
      polar bears.

PMID- 19754682
TI  - Abstracts of the American Academy for Cerebral Palsy and Developmental Medicine
      63rd Annual Meeting. September 23-26, 2009. Scottsdale, Arizona, USA.

PMID- 19754683
TI  - Abstracts of the Australasian College of Dermatologists Biennial Spring
      Conference. October 8-11, 2009. Hunter Valley, New South Wales, Australia.

PMID- 19754684
TI  - Secretory cells of the supraoptic nucleus have central as well as
      neurohypophysial projections.
AB  - Conventional neuroanatomical methods may fail to demonstrate the presence of
      axons that are finer than 1 microm in diameter because such processes are near or
      below the limit of resolution of the light microscope. The presence of such axons
      can, however, be readily demonstrated by recording. The most easily interpreted
      type of recording for this purpose is the demonstration of antidromic activation
      of the cell body following stimulation of the region through which the axon
      passes. We have exploited this technique in the hypothalamus and have
      demonstrated the presence of double axonal projections or axons branching very
      near the cell bodies of the secretory cells of the neurohypophysial system in the
      rat supraoptic nucleus. We found that a small proportion of supraoptic
      magnocellular cells could be antidromically activated both from the neural stalk
      and from elsewhere in the hypothalamus, including the suprachiasmatic nucleus (8
      cells of a total of 182) and the antero-ventral third ventricular region (AV3V; 4
      of 182 cells) near the organum vasculosum of the lamina terminalis (OVLT).
      Collision of antidromic and orthodromic spikes showed that the cells were clearly
      antidromically (rather than synaptically, or orthodromically) activated from both
      sites. A stimulus applied to one of the axons prevented propagation of a spike
      evoked by a pulse delivered to the other axon until sufficient time had elapsed
      after the first stimulus for the resultant spike to have propagated from the
      first stimulus site along one cell process (towards the cell body or branch
      point), and from this point along the other axonal branch to the second stimulus
      site (there was also a short additional delay period during which the axon at the
      site of the second stimulus recovered from its absolute refractory period). If
      the interval between the stimuli was progressively reduced, there came a point
      where the second spike failed. Such a clear demonstration of dual projections in
      a system where the cells were previously thought to have only a single axon
      raises the possibility that many nerve cells in the CNS have previously
      unsuspected projections.

PMID- 19754686
TI  - Bridging divides: patient and public involvement on both sides of the Atlantic.

PMID- 19754687
TI  - Social participation in health in Brazil and England: inclusion, representation
      and authority.
AB  - AIM: This article offers a brief description and analysis of public participation
      in health in Brazil and England in order to highlight different motivators and
      tensions within an acceptance of participation as official policy.
      SOURCES/METHODS: The article draws on a range of research in both countries and
      an analysis of official documents relating to participation. It is based on
      collaboration between researchers deriving from broad programmes of work on
      public participation in which the authors are involved. ARGUMENT: There is a
      tension between different principles underpinning collective public involvement
      in health both within and between countries. Different aspirations or claims have
      been made about what such participation will achieve and there are trade-offs
      between design principles that have consequences for issues such as who takes
      part and thus also for what can be achieved. The democratic origins of public
      participation are more evident in the Brazilian situation than in England, but
      there are still questions about the inclusivity of the practices through which
      this is achieved. The English picture is both more diverse and dynamic, but
      formal decision-making power of participatory forums is less than in Brazil.
      Whilst social justice claims for participation have been made in both countries,
      there is as yet limited evidence that these have been realized.

PMID- 19754688
TI  - Choice vs. voice? PPI policies and the re-positioning of the state in England and
      Wales.
AB  - CONTEXT AND THESIS: Changing patient and public involvement (PPI) policies in
      England and Wales are analysed against the background of wider National Health
      Service (NHS) reforms and regulatory frameworks. We argue that the growing
      divergence of health policies is accompanied by a re-positioning of the state vis
      a-vis PPI, characterized by different mixes of centralized and decentralized
      regulatory instruments. METHOD: Analysis of legislation and official documents,
      and interviews with policy makers. FINDINGS: In England, continued hierarchical
      control is combined with the delegation of responsibilities for the oversight and
      organization of PPI to external institutions such as the Care Quality Commission
      and local involvement networks, in support of the government's policy agenda of
      increasing marketization. In Wales, which has rejected market reforms and
      economic regulation, decentralization is occurring through the use of mixed
      regulatory approaches and networks suited to the small-country governance model,
      and seeks to benefit from the close proximity of central and local actors by
      creating new forms of engagement while maintaining central steering of service
      planning. Whereas English PPI policies have emerged in tandem with a pluralistic
      supply-side market and combine new institutional arrangements for patient
      'choice' with other forms of involvement, the Welsh policies focus on 'voice'
      within a largely publicly-delivered service. DISCUSSION: While the English
      reforms draw on theories of economic regulation and the experience of independent
      regulation in the utilities sector, the Welsh model of local service integration
      has been more influenced by reforms in local government. Such transfers of
      governance instruments from other public service sectors to the NHS may be
      problematic.

PMID- 19754689
TI  - User involvement in the construction of a mental health charter: an exercise in
      communicative rationality?
AB  - BACKGROUND: This paper uses Jurgen Habermas's Theory of Communicative Action as a
      lens through which to examine the development of a local mental health charter.
      OBJECTIVE: To assess whether the Charter represents the product of a
      communicatively rational process. RESEARCH DESIGN AND SETTING: The paper is based
      on an analysis of the text of the Charter, and on documentation relating to its
      development, including notes of discussion groups used to identify its themes.
      FINDINGS: An analysis of the notes of the discussion groups against the text of
      the Charter shows that the Charter's themes are based broadly on the views
      generated in the discussion groups. However, they also draw on norms derived from
      wider discourses not reflected in the discussion groups, and exclude other
      specific local issues. The strength of feeling expressed in the discussion groups
      is also toned down in the language of the Charter. DISCUSSION: The development of
      the Charter was based on a participatory process that can be said to have
      contained elements of both communicative and strategic rationality. The strategic
      rationality involved in translating service users' views into language that would
      be acceptable to those working in the system can be seen as necessary for the
      Charter to succeed in bringing about change. In drawing also on communicatively
      generated norms from the wider public sphere the Charter can be seen as
      reflecting a form of generalized communicative rationality. CONCLUSION: The
      Charter represents a 'sluice' by which communicative rationality is drawn into
      the mental health system.

PMID- 19754690
TI  - Involving the public through participatory visual research methods.
AB  - OBJECTIVES: To show how providing cameras to patients and community residents can
      be effective at involving the public in generating understanding of consumer,
      community, and health system problems and strengths. BACKGROUND: Health-care
      institutions and systems may seek to include consumer perspectives on health and
      health care yet be challenged to involve the most vulnerable sectors, be they
      persons with disabilities or persons with low socio-economic status living in
      societies where a top-down approach to policy is the norm. METHODS: Drawing on
      study examples using photo-elicitation and photovoice in Morocco and the United
      States, the authors explore issues of planning, data analysis, ethical concerns
      and action related to using participatory visual methods in different cultural
      and political contexts. RESULTS: Visual data generated by consumers can be
      surprising and can identify health system problems and strengths omitted from
      data gathered using other means. Statistical data may convince policy makers of
      the need to address a problem. Participant visual data may in turn encourage
      policy maker attention and action. CONCLUSION: Health system decision making may
      be improved by having a broader range of data available. Participant-generated
      visual data may support data gathered using traditional methods, or provide a
      reality check when compared with data generated by organizations, researchers and
      policy makers. The two study examples model innovative ways to surface health and
      health-care issues as they relate to consumers' real lives and engage vulnerable
      groups in systems change, even in contexts where expressing opinions might be
      seen as a risky thing to do.

PMID- 19754691
TI  - Revolution or evolution: the challenges of conceptualizing patient and public
      involvement in a consumerist world.
AB  - BACKGROUND: Changing the relationship between citizens and the state is at the
      heart of current policy reforms. Across England and the developed world, from
      Oslo to Ontario, Newcastle to Newquay, giving the public a more direct say in
      shaping the organization and delivery of healthcare services is central to the
      current health reform agenda. Realigning public services around those they serve,
      based on evidence from service user's experiences, and designed with and by the
      people rather than simply on their behalf, is challenging the dominance of
      managerialism, marketization and bureaucratic expertise. Despite this attention
      there is limited conceptual and theoretical work to underpin policy and practice.
      OBJECTIVE: This article proposes a conceptual framework for patient and public
      involvement (PPI) and goes on to explore the different justifications for
      involvement and the implications of a rights-based rather than a regulatory
      approach. These issues are highlighted through exploring the particular evolution
      of English health policy in relation to PPI on the one hand and patient choice on
      the other before turning to similar patterns apparent in the United States and
      more broadly. CONCLUSIONS: A framework for conceptualizing PPI is presented that
      differentiates between the different types and aims of involvement and their
      potential impact. Approaches to involvement are different in those countries that
      adopt a rights-based rather than a regulatory approach. I conclude with a
      discussion of the tension and interaction apparent in the globalization of both
      involvement and patient choice in both policy and practice.

PMID- 19754692
TI  - Goal achievement as a patient-generated outcome measure for stress urinary
      incontinence.
AB  - OBJECTIVES: To explore women's goals and goal attainment for the conservative and
      surgical treatment of stress urinary incontinence (SUI), and to examine the
      feasibility of Goal Attainment Scaling (GAS) as an outcome measure in this
      population. BACKGROUND: Despite the range of treatments for SUI, little is known
      about the outcomes patients consider important. Current instruments measure the
      impact of SUI on the ability to live a 'normal' life without addressing what
      normal looks like for the patient. Patient-generated measures that address what a
      patient aims to achieve may fill this gap. DESIGN: A mixed-methods exploratory
      design combined semi-structured interviews with validated questionnaires and
      individualized rating of goal achievement. SETTING AND PARTICIPANTS PARTICIPANTS:
      with SUI (n = 18) were interviewed in their homes prior to initiation of
      treatment and 3-6 months afterwards. MAIN VARIABLES: Participants reported
      individualized goals pre-treatment and rated goal attainment after surgical and
      conservative therapy. Quality of life impact and change were measured using short
      forms of the Incontinence Impact Questionnaire and Urinary Distress Inventory.
      RESULTS: Women expressed a median of four highly individualized treatment-related
      goals but goal achievement following conservative treatment was poor. GAS was not
      feasible as an outcome measure; women readily identified personal goals but could
      not independently identify graded levels of attainment for each goal.
      CONCLUSIONS: Although further work is needed to examine the most feasible, valid,
      and reliable method of measuring goal achievement in research, asking patients
      with UI to identify pre-treatment goals may provide useful information to guide
      treatment-related decision making.

PMID- 19754693
TI  - Men's and carers' experiences of care for prostate cancer: a narrative literature
      review.
AB  - OBJECTIVE: To review studies of patients' and carers' experience of prostate
      cancer care. DESIGN: Narrative literature review. METHODS: Search strategies were
      developed for the following databases: MEDLINE (1966-2006), EMBASE (1980-2006),
      CINAHL (1982-2006) and PsycINFO (1987-2006). A search of SIGLE (System for
      Information on Grey Literature in Europe) was also undertaken. Experience was
      defined as patients' and carers' reports of how care was organized and delivered
      to meet their needs. A narrative summary of the included papers was undertaken.
      RESULTS: A total of 90 relevant studies were identified. Most studies reported on
      experiences of screening, diagnosis, the treatment decision, treatment and post
      initial treatment. Few studies reported on experiences of the stages of referral,
      testing, and further treatment and palliative care, and no studies reported on
      monitoring or terminal care. CONCLUSIONS: Although some phases of care have not
      been investigated in detail, there is evidence that: (i) many patients have a low
      level of knowledge of prostate cancer; (ii) patients with prostate cancer and
      their carers need information throughout the care pathway to enable them to
      understand the diagnosis, treatment options, self-care and support available; and
      (iii) increasing patient knowledge and understanding of prostate cancer (e.g.
      through interventions) are often associated with a more active role in decision
      making (e.g. screening, treatment decision).

PMID- 19754694
TI  - Pandemic influenza communication: views from a deliberative forum.
AB  - OBJECTIVE: To use a deliberative forum to elicit community perspectives on
      communication about pandemic influenza planning, and to compare these findings
      with the current Australian national communication strategy. DESIGN: Deliberative
      forum of 12 persons randomly selected from urban South Australia. Forum members
      were briefed by experts in infection control, virology, ethics and public policy
      before deliberating on four key questions: what, how and when should the
      community be told about pandemic influenza and by whom? RESULTS: The forum
      recommended provision of detailed and comprehensive information by credible
      experts, rather than politicians, using a variety of media including television
      and internet. Recommendations included cumulative communication to build
      expertise in the community, and specific strategies to include groups such as
      young people, people with physical or mental disabilities, and rural and remote
      communities. Information provided should be practical, accurate, and timely, with
      no 'holding back' about the seriousness of a pandemic. The forum expressed
      confidence in the expert witnesses, despite the acknowledged uncertainty of many
      of the predictions. DISCUSSION AND CONCLUSION: The deliberative forum's
      recommendations were largely consistent with the Australian national pandemic
      influenza communication strategy and the relevant literature. However, the forum
      recommended: release of more detailed information than currently proposed in the
      national strategy; use of non-political spokespersons; and use of novel
      communication methods. Their acceptance of uncertainty suggests that policy
      makers should be open about the limits of knowledge in potentially threatening
      situations. Our findings show that deliberative forums can provide community
      perspectives on topics such as communication about pandemic influenza.

PMID- 19754696
TI  - Relationship between traumatic dental injuries and obesity in Brazilian
      schoolchildren.
AB  - The aim of this study was to investigate if obesity is associated to the
      occurrence of dental trauma in the permanent anterior teeth of adolescents from
      Recife, Brazil. It included a random sample of 1046 boys and girls aged 12 years
      attending both public and private schools. The sample size was calculated using a
      95% confidence interval level; a statistical significance of 5%; and an odds
      ratio of 1.55. The sample selection was carried out in two stages: first, schools
      were selected by simple sampling, and then children were chosen using a
      proportionality coefficient. Data were collected through clinical examinations
      and interviews, after examiner calibration. Dental trauma was classified
      according to ANDREASEN; ANDREASEN criteria. Obesity was considered according to
      National Center of Health Statistics - NCHS (USA) procedures for the assessment
      of nutritional status. Subjects were considered as non-obese when the observed
      percentile was < or = 97, while obese adolescent presented percentiles >97. Data
      were summarized and analyzed using the statistical software SPSS. The prevalence
      of traumatic injuries was higher among obese boys than obese girls (17.2% and
      16.2%, respectively), but there were no statistically significant differences
      between traumatic dental injuries and obesity (P > 0.05). It was concluded that
      the presence of obesity was not associated to traumatic dental injuries in
      adolescents from Recife, Brazil.

PMID- 19754697
TI  - Evaluation of volumetry and density of mandibular symphysis bone grafts by three
      dimensional computed tomography.
AB  - PURPOSE: Bone grafting before implant placing can improve the treatment in
      traumatized or regular implant patients. The aim of this study was to evaluate
      the density and maximum amount of harvestable bone graft in the mandibular
      symphysis. MATERIALS AND METHODS: Data from 15 CT-scans were obtained from 15
      adult patients (10 male/five female) for the purposes of this study. The CT data,
      in DICOM format, were read into Mimics software from Materialize (Leuven,
      Belgium), with a slice thickness of 0.5 mm. The volume, density, and dimensions
      based on Hounsfield units (HU) were measured on the 3D symphyseal bone graft
      using Mimics software. RESULTS: The average bone volume calculated from the
      mandibular symphysis was 3491.08 +/- 772.12 mm(3). The average sized
      corticocancellous block that was measured was 38.75 x 11.05 x 7.80 mm. The mean
      bone density was 958.95 +/- 98.11 HU. CONCLUSION: The use of three-dimensional
      computed tomography (3D CT) in combination with a software program is a reliable
      means of determining the density of graft, evaluating maximal volume and
      dimensions of the graft that can be harvested from the mandibular symphysis
      region.

PMID- 19754698
TI  - Calcium ion diffusion levels from MTA and ApexCal in simulated external root
      resorption at middle third of the root.
AB  - The purpose of this study was to investigate diffusion of calcium ions through
      exposed dentinal tubules following intracanal application of MTA and ApexCal.
      Thirty extracted anterior teeth were divided into three groups (n = 10): Group I:
      root canal prepared teeth with unfilled canals served as control; Group II: root
      canal space filled with MTA; Group III: root canal space filled with ApexCal. The
      teeth were decoronated, and root canal prepared to its working length and
      irrigated with EDTA and NaOCl. To simulate external root resorption, defects were
      created on the external surface of the root at the middle thirds. MTA/ApexCal was
      introduced into the canal and entrance sealed with IRM. The teeth were then
      coated with varnish except at the defect. Each tooth was immersed in a vial
      containing deionized water after which the release of Ca(2+)from the defects into
      the deionized water was measured at 1, 7, 12, 14, and 28 days.
      Ca(2+)concentrations of the immersion media were measured using a spectrometer.
      The post hoc-Bonferroni Alpha test (with mean difference significant at the 0.05
      level) was done to statistically analyse the results using spss 11.5 software for
      Windows. The results showed greater calcium release by ApexCal than MTA with a
      significant increase with time. Within the experimental conditions of the present
      study APEX CAL may potentially be used in cases of root resorption.

PMID- 19754699
TI  - Knowledge of teachers and students in physical education's faculties regarding
      first-aid measures for tooth avulsion and replantation.
AB  - The aim of the present cross-sectional study was to investigate the knowledge of
      undergraduate students and teachers at all physical education courses in the city
      of Belo Horizonte (Brazil) regarding first-aid measures to be taken following
      tooth avulsion as well as the need for the preventative use of mouth guards. The
      sample consisted of 442 individuals (Group 1: 53 teachers; Group 2: 389
      undergraduate students). Data collection was carried out with the administration
      of a questionnaire with both objective and subjective questions addressing
      definitions, first-aid measures in cases of avulsion and tooth replantation,
      together with an assessment of the use and indication of mouth guards. Data
      analysis involved descriptive statistics and the chi-square test. The results
      revealed that 45.1% of the participants in both groups knew what a tooth
      replantation was. However, 91.6% judged themselves incapable of performing an
      immediate replantation. Among the overall sample, 45.9% has no knowledge on first
      aid measures regarding tooth avulsion; sending the patient with an avulsed tooth
      to the dentist was the most often cited measure (42.3%). Immediate replantation
      was cited by 20.6% of the individuals in Group 1 and 5.9% of the individuals in
      Group 2 (P = 0.009). Regarding the storage medium, 17.1% of the individuals would
      keep the avulsed tooth in a dry medium. The majority of participants (58.3%)
      stated that the ideal extra-alveolar time for replantation was more than 360 min.
      Although 74% of the overall sample stated having knowledge of mouth guards, few
      reported making use or indicating the use of this piece of equipment. The present
      study revealed that the majority of teachers and undergraduate students of
      physical education courses do not have adequate knowledge regarding first-aid
      measures for tooth avulsion and do not use or indicate the use of mouth guards
      during sports activities.

PMID- 19754700
TI  - Traumatic lesions from congenital insensitivity to pain with anhidrosis in a
      pediatric patient: dental management.
AB  - Congenital insensitivity to pain with anhidrosis is a rare autosomal-recessive
      disorder characterized by unexplained fever episodes, anhidrosis, pain
      insensitivity, self-mutilating behavior, and mental retardation. The lack of
      sensitivity to pain results in traumatic lesions, such as ulcers, fractures,
      burns, bites, scars, and digital amputations. Several methods have been suggested
      to treat these patients; however, appropriate management is difficult, especially
      when the mutilation is particularly severe. This report describes the case of a 2
      year-old female patient who had severe self-mutilating injuries to her tongue,
      hands, lips, and oral mucosa caused by biting. The patient presented digital
      amputation and also a premature loss of a permanent tooth germ during the
      treatment. The dental management is described and discussed. It is important to
      include the dentist on the multidisciplinary team to reduce the frequency and
      severity of the self-inflicted lesions in these patients, also to prevent
      complications.

PMID- 19754701
TI  - Late reposition of a lateral luxated maxillary incisor with an immature apex.
AB  - Here we describe an unusual trauma case. A recently erupted permanent upper-right
      incisor sustained a lateral luxation when a 5-year-old girl on a playground
      climbing net dropped off, catching the right upper incisor in the net. The tooth
      was laterally luxated in vestibular direction, and no other signs of injury
      occurred. A dental practitioner could not reposition the bony locked tooth. Four
      days later, the girl came to our clinic, and we performed an incomplete
      repositioning of the tooth and made a flexible splint. Controls were made at 1,
      6, and 12 weeks and at 6, 12, 18, and 24 months later. The 24-month follow-up
      clinical examination revealed the patient to be asymptomatic and the tooth to be
      completely functional, and the recall radiograph showed further apical root
      growth. The implications of a late incomplete reposition of laterally luxated
      permanent teeth with immature apices are discussed.

PMID- 19754702
TI  - Epistasis, constraints, and coevolution.

PMID- 19754703
TI  - Bio.

PMID- 19754704
TI  - The rise and evolution of the cambial variant in Bignonieae (Bignoniaceae).
AB  - Cambial variants represent a form of secondary growth that creates great stem
      anatomical diversity in lianas. Despite the importance of cambial variants,
      nothing is known about the developmental mechanisms that may have led to the
      current diversity seen in these stems. Here, a thorough anatomical analysis of
      all genera along the phylogeny of Bignonieae (Bignoniaceae) was carried out in
      order to detect when in their ontogeny and phylogeny there were shifts leading to
      different stem anatomical patterns. We found that all species depart from a
      common developmental basis, with a continuous, regularly growing cambium. Initial
      development is then followed by the modification of four equidistant portions of
      the cambium that reduce the production of xylem and increase the production of
      phloem, the former with much larger sieve tubes and an extended lifespan. In most
      species, the formerly continuous cambium becomes disjunct, with cambial portions
      within phloem wedges and cambial portions between them. Other anatomical
      modifications such as the formation of multiples of four phloem wedges, multiple
      dissected phloem wedges, and included phloem wedges take place thereafter. The
      fact that each novel trait raised on the ontogenetic trajectory appeared in
      subsequently more recent ancestors on the phylogeny suggests a recapitulatory
      history. This recapitulation is, however, caused by the terminal addition of
      evolutionary novelties rather than a truly heterochronic process. Truly
      heterochronic processes were only found in shrubby species, which resemble
      juveniles of their ancestors, as a result of a decelerated phloem formation by
      the variant cambia. In addition, the modular evolution of phloem and xylem in
      Bignonieae seems to indicate that stem anatomical modifications in this group
      occurred at the level of cambial initials.

PMID- 19754705
TI  - The insect upper lip (labrum) is a nonsegmental appendage-like structure.
AB  - The insect upper lip--the labrum--is a lobe-like structure anterior to the mouth
      opening. Whether the labrum represents a fused pair of segmental appendages or
      evolved independently is heavily debated. Here, we identify additional
      similarities of the regulatory gene network active in labrum and trunk
      appendages. However, we do not find a labral parasegment boundary and we show
      that labral Tc-Dll expression is independent of Tc-wg and Tc-hh signals. In
      contrast, Tc-Dll expression in all trunk appendages does require these signals.
      Finally, we identify crucial differences between the location of the labrum and
      trunk appendages: the labrum develops in median rather than lateral tissues and
      is part of an anterior nonsegmental tissue marked by and dependent on Tc-six3
      activity. To reconcile these seeming contradictory results, we propose that the
      genetic network evolved in either labrum or trunk appendages and became
      redeployed at a novel location to form the other structure.

PMID- 19754706
TI  - Eyespot evolution: phylogenetic insights from Junonia and related butterfly
      genera (Nymphalidae: Junoniini).
AB  - Butterfly eyespots have been the focus of a number of developmental and
      evolutionary studies. However, a phylogenetic component has rarely been
      explicitly incorporated in these studies. In this study, I utilize a phylogeny to
      trace the evolution of eyespot number and position on the wing in a group of
      nymphalid butterflies, the subtribe Junoniini. These butterflies have two kinds
      of eyespot arrangements which I refer to as Serial and Individual. In the Serial
      arrangement, eyespots are placed in a series on compartments 1-6 (counting from
      the anterior wing margin). In the Individual arrangement, eyespots are isolated
      on specific compartments, ranging from 1 to 4 in number. This can be divided into
      four subtypes based on the number and positions of eyespots. I map the evolution
      of these five arrangements over a phylogeny of Junoniini reconstructed with ca.
      3000 base pairs of sequence data from three genes. The results show that almost
      all arrangements have evolved at least twice, with multiple shifts between them
      by addition and deletion of eyespots. I propose a model involving genetic or
      developmental coupling between eyespots in specific compartments to explain these
      shifts. I discuss their evolution in light of existing knowledge about their
      development. I also discuss potential explanations for functional significance of
      the eyespot patterns found in the group. Differential selection for and against
      eyespots, both at different times over the phylogeny and in different regions,
      have driven the evolution of eyespot arrangements. The study throws open many
      questions about the adaptive significance of eyespots and the developmental
      underpinnings of the various arrangements.

PMID- 19754707
TI  - Shared and divergent expression domains on mimetic Heliconius wings.
AB  - Heliconius butterfly wing patterns show repeated convergence between species and
      have adaptive value in mimicry and mate choice, offering an opportunity to
      connect adaptive changes in phenotype with their underlying genotypes. Here we
      study forewing ommochrome pigmentation in Heliconius melpomene. We clone two new
      ommochrome pathway genes for the Lepidoptera, karmoisin and kynurenine
      formamidase (kf ), and analyze the expression patterns of all known ommochrome
      genes across pupal wing development. In combination with published work, this
      generates the first comparative gene expression data for the co-mimics Heliconius
      erato and H. melpomene. In both species cinnabar expression correlates with the
      forewing band, but the expression pattern of vermillion differs significantly
      between the mimics. This demonstrates that both shared and divergent expression
      patterns are associated with mimetic phenotypes between Heliconius species. Two
      genes not studied in H. erato, scarlet and possibly kf, also show enhanced
      expression in the forewing band of H. melpomene, implying co-ordinated
      upregulation of several members of this biosynthetic pathway during pattern
      formation.

PMID- 19754708
TI  - Orthologs of key vertebrate neural genes are expressed during neurogenesis in the
      annelid Platynereis dumerilii.
AB  - The molecular mechanisms underlying the formation and patterning of the nervous
      system are relatively poorly understood for lophotrochozoans (like annelids) as
      compared with ecdysozoans (especially Drosophila) and deuterostomes (especially
      vertebrates). Therefore, we have undertaken a candidate gene approach to study
      aspects of neurogenesis in a polychaete annelid Platynereis dumerilii. We
      determined the spatiotemporal expression for Platynereis orthologs of four genes
      (SoxB, Churchill, prospero/Prox, and SoxC) known to play key roles in vertebrate
      neurogenesis. During Platynereis development, SoxB is expressed in the
      neuroectoderm and its expression switches off when committed neural precursors
      are formed. Subsequently, Prox is expressed in all differentiating neural
      precursors in the central and peripheral nervous systems. Finally, SoxC and
      Churchill are transcribed in patterns consistent with their involvement in neural
      differentiation. The expression patterns of Platynereis SoxB and Prox closely
      resemble those in Drosophila and vertebrates--this suggests that orthologs of
      these genes play similar neurogenic roles in all bilaterians. Whereas Platynereis
      SoxC, like its vertebrate orthologs, plays a role in neural cell differentiation,
      related genes in Drosophila do not appear to be involved in neurogenesis.
      Finally, conversely to Churchill in Platynereis, vertebrate orthologs of this
      gene are expressed during neuroectoderm formation, but not later during nerve
      cell differentiation; in the insect lineage, homologs of these genes have been
      secondarily lost. In spite of such instances of functional divergence or loss,
      the present study shows conspicuous similarities in the genetic control of
      neurogenesis among bilaterians. These commonalities suggest that key features of
      the genetic program for neurogenesis are ancestral to bilaterians.

PMID- 19754709
TI  - Expression of Dazl and Vasa in turtle embryos and ovaries: evidence for inductive
      specification of germ cells.
AB  - In bilaterian animals, germ cells are specified by the inductive/regulative mode
      or the predetermined (germ plasm) mode. Among tetrapods, mammals and urodeles use
      the inductive mode, whereas birds and anurans use the predetermined mode. From
      histological data it has been predicted that some reptiles including turtles use
      the inductive mode. Examining turtle oocytes, we find that Dazl RNA, Vasa RNA,
      and Vasa protein are not localized, suggesting that germ plasm is not present. In
      turtle embryos at somite stages, primordial germ cells (PGCs) expressing Dazl lie
      on a path from the lateral posterior extraembryonic endoderm through the gut to
      the gonad as previously described. In gastrulating embryos, cells expressing Dazl
      are found in the blastoporal plate and subsequently below the blastoporal plate,
      indicating that PGCs are generated at the equivalent of the early posterior
      primitive streak of mammals. Vasa RNA is expressed in somatic cells of gastrula
      to early somite stages, and Vasa RNA and protein are expressed in PGCs of later
      embryos. Taken together the evidence strongly suggests that turtles, and other
      reptiles (lacertoid lizards) with the same location of PGCs in embryos, use the
      inductive mode of germ cell specification. Phylogenetic analysis of the available
      evidence supports the following hypotheses: (1) the inductive mode is basal among
      reptiles, indicating that this mode was maintained as basal tetrapods evolved to
      amniotes, (2) the predetermined mode arose twice within reptiles, and (3) the
      induced mode may be used in several lepidosaurs whose PGCs are located in an
      unusual pattern distributed around the embryo.

PMID- 19754710
TI  - Heterochronic shift between early organogenesis and migration of cephalic neural
      crest cells in two divergent evolutionary phenotypes of archosaurs: crocodile and
      ostrich.
AB  - Living archosaurs (crocodiles and birds) represent an intriguing evo-devo model
      system. Although close in phylogenetic relationship, the two lineages show
      considerable divergence in trends of phenotypic evolution. The head anatomy of
      recent crocodilians has changed little in comparison with that of their
      crocodylomorph ancestors. The head phenotype of the avians (birds), as well as
      some non-avian theropods, shows numerous evolutionary innovations that differ
      considerably from the crocodylomorph pattern. Most of the novel head structures,
      such as features of the craniofacial skeleton, cranial nerves, head muscles, and
      integument are derived from the same cellular source common to all archosaurs,
      the cephalic neural crest (CNC). Therefore, other factors must be involved in the
      developmental disparity of homologous structures in the aforementioned lineages.
      The present study analyzes the earliest developmental events that are associated
      with the appearance of the neural crest cells in the two archosaur models:
      Crocodylus niloticus and Struthio camelus. I found that both models share unique
      developmental features, the presence of an unpaired, rostrally migrating
      population of CNC cells, showing that the two are closely related to each other.
      On the other hand, the crocodile and the ostrich differ substantially in (1)
      timing, (2) duration, and (3) expression patterns of the CNC. Compared with the
      crocodile, the CNC cells in the ostrich (1) migrate much later into the embryonic
      head, (2) but relocate to their terminal positions faster, and (3) take
      specifically directed migratory routes in the mandibular/oral region and
      head/trunk-interface regions. I suggest that accelerated relocation of CNC cells
      combined with delayed head organogenesis may represent important innovative
      conditions in the developmental evolution of a new archosaur head phenotype.

PMID- 19754711
TI  - Regulation of expression of zebrafish (Danio rerio) insulin-like growth factor 2
      receptor: implications for evolution at the IGF2R locus.
AB  - The insulin-like growth factor 2 receptor (IGF2R) is an unusual multifunctional
      receptor that interacts with a diverse variety of ligands. While the receptor has
      been well-characterized in mammals, little is known of its biology in other
      vertebrates. In this report, we characterize the expression of the zebrafish
      (Danio rerio) ortholog of the IGF2R gene. We show that two distinct, cell-type
      specific promoters drive transcription of zebrafish igf2r and that these encode
      receptor isoforms that differ in their amino termini. Both promoters are active
      in adult fish and during embryonic development, but the proximal promoter
      generates more abundant transcripts. The 5'-UTR of the more abundantly expressed
      transcript contains several AUGs upstream of the main start codon, and these
      negatively regulate translation of a downstream reporter gene. Comparative
      sequence analysis shows that upstream AUGs (uAUGs) are a feature of IGF2R genes
      in several other vertebrates, including Xiphophorus, Xenopus, chicken, platypus,
      and opossum, but not in eutherian mammals. The IGF2R is imprinted in marsupial
      and placental mammals, and this transcriptional control of receptor abundance was
      proposed to have evolved following acquisition of an insulin-like growth factor 2
      (IGF2) binding site by the ancestral receptor. Our observations suggest that
      receptor abundance was regulated at translation in ancestral vertebrates, before
      acquisition of an IGF2 binding site. We propose that evolution of imprinting at
      the mammalian IGF2R may have facilitated the loss of negative regulation of
      translation conferred by uAUGs.

PMID- 19754713
TI  - Tracking the origins of the bilaterian Hox patterning system: insights from the
      acoel flatworm Symsagittifera roscoffensis.
AB  - Genes of the Hox cluster encode for transcriptional regulators that show
      collinear expression along the anteroposterior (AP) body axis in all bilateral
      animals. However, it is still unclear when in the evolutionary history of
      bilaterians the Hox system first conferred positional identity along the AP-axis.
      Recent molecular phylogenies have convincingly shown that the acoel flatworms,
      traditionally classified within the Platyhelminthes, are the sister group of the
      remaining Bilateria, branching out before the common ancestor of protostomes, and
      deuterostomes (the so-called PDA). This key phylogenetic position offers the
      opportunity to search for the presence and early role of Hox cluster genes to
      pattern the AP axis in acoels. Here, we report on the cloning, genomic
      arrangement, and expression domains of Hox genes in Symsagittifera roscoffensis.
      Three Hox genes were detected: one from each of the major groups of Hox genes,
      which are anterior, central, and posterior. In bacterial artificial chromosome
      cloning, sequencing, and chromosomal fluorescence in situ hybridization, Hox
      genes were not observed as being clustered in a unique genomic region.
      Nevertheless, despite its dispersion within the genome, Hox genes are expressed
      in nested domains along the AP axis in the juvenile worm. The basic set of Hox
      genes in acoels and their coarse nested spatial deployment might be the first
      indicators of the role of Hox genes in the evolution of bilateral symmetry and AP
      positional identity from a hypothetical radial ancestor.

PMID- 19754712
TI  - An evolutionary transition of Vasa regulation in echinoderms.
AB  - Vasa, a DEAD box helicase, is a germline marker that may also function in
      multipotent cells. In the embryo of the sea urchin Strongylocentrotus purpuratus,
      Vasa protein is posttranscriptionally enriched in the small micromere lineage,
      which results from two asymmetric cleavage divisions early in development. The
      cells of this lineage are subsequently set aside during embryogenesis for use in
      constructing the adult rudiment. Although this mode of indirect development is
      prevalent among echinoderms, early asymmetric cleavage divisions are a derived
      feature in this phylum. The goal of this study is to explore how vasa is
      regulated in key members of the phylum with respect to the evolution of the
      micromere and small micromere lineages. We find that although striking
      similarities exist between the vasa mRNA expression patterns of several sea
      urchins and sea stars, the time frame of enriched protein expression differs
      significantly. These results suggest that a conserved mechanism of vasa
      regulation was shifted earlier in sea urchin embryogenesis with the derivation of
      micromeres. These data also shed light on the phenotype of a sea urchin embryo
      upon removal of the Vasa-positive micromeres, which appears to revert to a basal
      mechanism used by extant sea stars and pencil urchins to regulate Vasa protein
      accumulation. Furthermore, in all echinoderms tested here, Vasa protein and/or
      message is enriched in the larval coelomic pouches, the site of adult rudiment
      formation, thus suggesting a conserved role for vasa in undifferentiated
      multipotent cells set aside during embryogenesis for use in juvenile development.

PMID- 19754714
TI  - Molecular markers comparing the extremely simple body plan of dicyemids to that
      of lophotrochozoans: insight from the expression patterns of Hox, Otx, and
      brachyury.
AB  - Because of their extremely simple body plan, dicyemids have long been the subject
      of phylogenetic controversy, regarding whether their body plan reflects their
      primitiveness or a degeneration from complex metazoans. Several studies have
      argued that the simple body plan of dicyemids are likely secondarily derived from
      higher lophotrochozoan animals, as a result of their endoparasitic, or
      endosymbiotic, lifestyle in the cephalopod kidney. To clarify the evolution of
      their simple body plan, we investigated the developmental expression patterns of
      three important regulatory genes, the central type Hox gene (DoxC), otx, and
      brachyury homologs in the dicyemid mesozoa, Dicyema orientale. DoxC was expressed
      in the trunk and tail of the asexually developing vermiform embryo, with clear
      anterior boundaries. Do-otx was expressed in the vegetal pole cells of the
      developing infusoriform embryos, suggesting that the invagination in infusoriform
      embryo is homologous to the gastrulation of other metazoans. Do-bra is expressed
      in the presumptive ventral cells, which are ventral to the opening of the urn
      cavity. The expression of Do-bra suggests that the urn cavity opening of the
      infusoriform embryo is comparable to the stomodium of trochophore larvae. These
      gene expression patterns provide molecular clues to trace the evolutionary
      history of degeneration in the dicyemid embryogenesis and life cycle from those
      of ancestral lophotrochozoan animals.

PMID- 19754715
TI  - Developmental constraints revealed by co-variation within and among molar rows in
      two murine rodents.
AB  - Morphological integration corresponds to interdependency between characters that
      can arise from several causes. Proximal causes of integration include that
      different phenotypic features may share common genetic sets and/or interact
      during their development. Ultimate causes may be the prolonged effect of
      selection favoring integration of functionally interacting characters, achieved
      by the molding of these proximal causes. Strong and direct interactions among
      successive teeth of a molar row are predicted by genetic and developmental
      evidences. Functional constraints related to occlusion, however, should have
      selected more strongly for a morphological integration of occluding teeth and a
      corresponding evolution of the underlying developmental and genetic pathways. To
      investigate how these predictions match the patterns of phenotypic integration,
      we studied the co-variation among the six molars of the murine molar row,
      focusing on two populations of house mice (Mus musculus domesticus) and wood mice
      (Apodemus sylvaticus). The size and shape of the three upper and lower molars
      were quantified and compared. Our results evidenced similar patterns in both
      species, size being more integrated than shape among all the teeth, and both size
      and shape co-varying strongly between adjacent teeth, but also between occluding
      teeth. Strong co-variation within each molar row is in agreement with
      developmental models showing a cascade influence of the first molar on the
      subsequent molars. In contrast, the strong co-variation between molars of the
      occluding tooth rows confirms that functional constraints molded patterns of
      integration and probably the underlying developmental pathways despite the low
      level of direct developmental interactions occurring among molar rows. These
      patterns of co-variation are furthermore conserved between the house mouse and
      the wood mouse that diverged >10 Ma, suggesting that they may constitute long
      running constraints to the diversification of the murine rodent dentition.

PMID- 19754716
TI  - Evolution of germ cell development in tetrapods: comparison of urodeles and
      amniotes.
AB  - The embryonic development of germ cells in tetrapods is described, focusing on
      groups with the inductive mode of germ cell specification. In mammals PGCs are
      induced early in the gastrulation process, they are internalized with future
      extraembryonic mesoderm in the early posterior primitive streak, and specified
      soon thereafter. Strong evidence indicates that a similar process occurs in
      turtles and some other reptiles. In amniotes, the PGCs appear well before
      formation of the gonad in the posterior trunk, resulting in a period in which
      they are located outside the embryo before their migration to the gonad. In
      contrast, in urodeles the PGCs appear relatively late, and throughout development
      maintain a position close to precursors of the somatic cells of the gonad so that
      migration is not required. In lampreys early development of germ cells is
      strikingly similar to that in urodeles, suggesting this is the primitive process.
      As amniotes evolved large yolky eggs and better access to nutrition, development
      of the posterior half of the trunk became more dependent on cell proliferation;
      this was followed or accompanied by a shift of early germ cell development to the
      equivalent of the early primitive streak. A similar process may have occurred as
      some basal vertebrates developed large yolky eggs.

PMID- 19754717
TI  - Structural and regulatory evolution of cellular electrophysiological systems.
AB  - Cellular electrophysiological systems, like developmental systems, appear to
      evolve primarily by means of regulatory evolution. It is suggested that
      electrophysiological systems share two key features with developmental systems
      that account for this dependence on regulatory evolution. For both systems,
      structural evolution has the potential to create significant problems of
      pleiotropy and both systems are predominantly computational in nature. It is
      concluded that the relative balance of physical and computational tasks that a
      biological system has to perform, combined with the probability that these tasks
      may have to change significantly during the course of evolution, will be major
      factors in determining the relative mix of regulatory and structural evolution
      that is observed for a given system. Physiological systems that directly
      interface with the environment will almost always perform some low-level physical
      task. In the majority of cases this will require evolution of protein function in
      order for the tasks themselves to evolve. For complex physiological systems a
      large fraction of their function will be devoted to high-level control functions
      that are predominantly computational in nature. In most cases regulatory
      evolution will be sufficient in order for these computational tasks to evolve.

PMID- 19754718
TI  - Foreword to the themed issue on correlative microscopy.

PMID- 19754719
TI  - Towards correlative imaging of plant cortical microtubule arrays: combining
      ultrastructure with real-time microtubule dynamics.
AB  - There are a variety of microscope technologies available to image plant cortical
      microtubule arrays. These can be applied specifically to investigate direct
      questions relating to array function, ultrastructure or dynamics.
      Immunocytochemistry combined with confocal laser scanning microscopy provides low
      resolution "snapshots" of cortical microtubule arrays at the time of fixation
      whereas live cell imaging of fluorescent fusion proteins highlights the dynamic
      characteristics of the arrays. High-resolution scanning electron microscopy
      provides surface detail about the individual microtubules that form cortical
      microtubule arrays and can also resolve cellulose microfibrils that form the
      innermost layer of the cell wall. Transmission electron microscopy of the arrays
      in cross section can be used to examine links between microtubules and the plasma
      membrane and, combined with electron tomography, has the potential to provide a
      complete picture of how individual microtubules are spatially organized within
      the cortical cytoplasm. Combining these high-resolution imaging techniques with
      the expression of fluorescent cytoskeletal fusion proteins in live cells using
      correlative microscopy procedures will usher in an radical change in our
      understanding of the molecular dynamics that underpin the organization and
      function of the cytoskeleton.

PMID- 19754720
TI  - Rapid combined light and electron microscopy on large frozen biological samples.
AB  - The use of large unfixed frozen tissue samples (10 x 10 x 5 mm(3)) for combined
      light microscopy (LM) and electron microscopy (EM) is described. First, cryostat
      sections are applied for various LM histochemical approaches including in situ
      hybridization, immunohistochemistry and metabolic mapping (enzyme
      histochemistry). When EM inspection is needed, the tissue blocks that were used
      for cryostat sectioning and are stored at -80 degrees C, are then fixed at 4
      degrees C with glutaraldehyde/paraformaldehyde and prepared for EM according to
      standard procedures. Ultrastructurally, most morphological aspects of normal and
      pathological tissue are retained whereas cryostat sectioning at -25 degrees C
      does not have serious damaging effects on the ultrastructure. This approach
      allows simple and rapid combined LM and EM of relatively large tissue specimens
      with acceptable ultrastructure. Its use is demonstrated with the elucidation of
      transdifferentiated mouse stromal elements in human pancreatic adenocarcinoma
      explants grown subcutaneously in nude mice. Combined LM and EM analysis revealed
      that these elements resemble cartilage showing enchondral mineralization and
      aberrant muscle fibres with characteristics of skeletal muscle cells.

PMID- 19754721
TI  - Correlative fluorescence and electron microscopy in tissues: immunocytochemistry.
AB  - Correlative microscopy is a collection of procedures that rely upon two or more
      imaging modalities to examine the same specimen. The imaging modalities employed
      should each provide unique information and the combined correlative data should
      be more information rich than that obtained by any of the imaging methods alone.
      Currently the most common form of correlative microscopy combines fluorescence
      and electron microscopy. While much of the correlative microscopy in the
      literature is derived from studies of model cell culture systems we have focused,
      primarily, on correlative microscopy in tissue samples. The use of tissue,
      particularly human tissue, may add constraints not encountered in cell culture
      systems. Ultrathin cryosections, typically used for immunoelectron microscopy,
      have served as the substrate for correlative fluorescence and electron
      microscopic immunolocalization in our studies. In this work, we have employed the
      bifunctional reporter FluoroNanogold. This labeling reagent contains both a
      fluorochrome and a gold-cluster compound and can be imaged by sequential
      fluorescence and electron microscopy. This approach permits the examination of
      exactly the same sub-cellular structures in both fluorescence and electron
      microscopy with a high level of spatial resolution.

PMID- 19754722
TI  - A review of high-pressure freezing preparation techniques for correlative light
      and electron microscopy of the same cells and tissues.
AB  - In this paper, we review some published studies using correlative light and
      electron microscopy methods. We further refined our criteria to include only
      those studies using live cells for light microscope and where high-pressure
      freezing was the method of specimen preparation for electron microscopy. High
      pressure freezing is especially important for some difficult-to-fix samples, and
      for optimal preservation of ultrastructure in samples larger than a few
      micrometres. How the light microscope observations are done is completely sample
      dependent, but the choice of high-pressure freezer depends on the speed required
      to capture (freeze) the biological event of interest. For events requiring high
      time resolution (in the 4-5 s range) the Leica EM PACT2 with rapid transfer
      system works well. For correlative work on structures of interest that are either
      non-motile or moving slowly (minutes rather than seconds), any make of high
      pressure freezer will work. We also report on some efforts to improve the
      capabilities of the Leica EM PACT2 rapid transfer system.

PMID- 19754723
TI  - Correlative fluorescence and transmission electron microscopy: an elegant tool to
      study the actin cytoskeleton of whole-mount (breast) cancer cells.
AB  - Elucidating the structure and dynamics of lamellipodia and filopodia in response
      to different stimuli is a topic of continuing interest in cancer cells as these
      structures may be attractive targets for therapeutic purposes. Interestingly, a
      close functional relationship between these actin-rich protrusions and
      specialized membrane domains has been recently demonstrated. The aim of this
      study was therefore to investigate the fine organization of these actin-rich
      structures and examine how they structurally may relate to detergent-resistant
      membrane (DRM) domains in the MTLn3 EGF/serum starvation model. For this reason,
      we designed a straightforward and alternative method to study cytoskeleton arrays
      and their associated structures by means of correlative fluorescence (/laser)-
      and electron microscopy (CFEM). CFEM on whole mounted breast cancer cells
      revealed that a lamellipodium is composed of an intricate filamentous actin web
      organized in various patterns after different treatments. Both actin dots and
      DRM's were resolved, and were closely interconnected with the surrounding
      cytoskeleton. Long actin filaments were repeatedly observed extending beyond the
      leading edge and their density and length varied after different treatments.
      Furthermore, CFEM also allowed us to demonstrate the close structural association
      of DRMs with the cytoskeleton in general and the filamentous/dot-like structural
      complexes in particular, suggesting that they are all functionally linked and
      consequently may regulate the cell's fingertip dynamics. Finally, electron
      tomographic modelling on the same CFEM samples confirmed that these extensions
      are clearly embedded within the cytoskeletal matrix of the lamellipodium.

PMID- 19754724
TI  - Molecular cryo-electron tomography of vitreous tissue sections: current
      challenges.
AB  - Electron tomography of vitreous tissue sections (tissue TOVIS) allows the study
      of the three-dimensional structure of molecular complexes in a near-native
      cellular context. Its usage is, however, limited by an unfortunate combination of
      noisy and incomplete data, by a technically demanding sample preparation
      procedure, and by a disposition for specimen degradation during data collection.
      Here we outline some major challenges as experienced from the application of
      TOVIS to human skin. We further consider a number of practical measures as well
      as theoretical approaches for its future development.

PMID- 19754725
TI  - Correlative microscopy: a potent tool for the study of rare or unique cellular
      and tissue events.
AB  - Biological studies have relied on two complementary microscope technologies -
      light (fluorescence) microscopy and electron microscopy. Light microscopy is used
      to study phenomena at a global scale to look for unique or rare events, and it
      also provides an opportunity for live imaging, whereas the forte of electron
      microscopy is the high resolution. Traditionally light and electron microscopy
      observations are carried out in different populations of cells/tissues and a
      'correlative' inference is drawn. The advent of true correlative light-electron
      microscopy has allowed high-resolution imaging by electron microscopy of the same
      structure observed by light microscopy, and in advanced cases by video
      microscopy. Thus a rare event captured by low-resolution imaging of a population
      or transient events captured by live imaging can now also be studied at high
      resolution by electron microscopy. Here, the potential and difficulties of this
      approach, along with the most impressive breakthroughs obtained by these methods,
      are discussed.

PMID- 19754726
TI  - Photooxidation technology for correlated light and electron microscopy.
AB  - The combination of the capabilities of light microscopical techniques with the
      power of resolution of electron microscopy along with technical advances has led
      to a gradual decline of the gap between classical light and electron microscopy.
      Among the correlative techniques using the synergistic opportunities,
      photooxidation methods have been established as valuable tools for visualizing
      cell structures at both light and electron microscopic level. Fluorescent dyes
      are used to oxidize the substrate diaminobenzidine, which in its oxidized state
      forms fine granular precipitates. Stained with osmium, the diaminobenzidine
      precipitates are well discernible in the electron microscope, thus labelling and
      defining the cellular structures, which at light microscopy level are recorded by
      fluorescent probes. The underlying photooxidation reaction is based on the
      excitation of free oxygen radicals that form upon illumination of fluorochromes;
      this is a central step in the procedure, which mainly influences the success of
      the method. This article summarizes basic steps of the technology and progresses,
      shows efforts and elaborated pathways, and focuses on methodical solutions as to
      the applicability of different fluorochromes, as well as conditions for fine
      structural localizations of the reaction products.

PMID- 19754727
TI  - Focused ion beam-scanning electron microscope: exploring large volumes of
      atherosclerotic tissue.
AB  - Atherogenesis is a pathological condition in which changes in the ultrastructure
      and in the localization of proteins occur within the vasculature during all
      stages of the disease. To gain insight in those changes, high-resolution imaging
      is necessary. Some of these changes will only be present in a small number of
      cells, positioned in a 'sea' of non-affected cells. To localize this relatively
      small number of cells, there is a need to first navigate through a large area of
      the sample and subsequently zoom in onto the area of interest. This approach
      enables the study of specific cells within their in vivo environment and enables
      the study of (possible) interactions of these cells with their surrounding
      cells/environment. The study of a sample in a correlative way using light and
      electron microscopy is a promising approach to achieve this; however, it is very
      laborious and additional ultrastructural techniques might be very valuable to
      find the places of interest. In this report we show that the focused ion beam
      scanning electron microscope is a powerful tool to study biological specimens in
      a correlative way. With this microscope one can scan for the area of interest at
      low magnification, in this case the atherosclerotic plaque, and subsequently zoom
      in, for further analysis on an ultrastructural level, rendering valuable and
      detailed two- and three-dimensional information of, in this case, the endothelial
      cells and the vessel wall. Moreover, in combination with pre-embedment labelling
      of surface exposed antigens, the method allows insight into the 3D distribution
      of these markers.

PMID- 19754728
TI  - What will 21th-century hospitals for the care of patients with highly infectious
      diseases look like?

PMID- 19754729
TI  - The European network of Biosafety-Level-4 laboratories: enhancing European
      preparedness for new health threats.
AB  - Emerging and re-emerging infections and possible bioterrorism acts will continue
      to challenge both the medical community and civilian populations worldwide,
      urging health authorities to respond rapidly and effectively. Established in
      2005, the European Community (EC)-funded European Network of Biosafety-Level-4
      laboratories (Euronet-P4), which brings together the laboratories in Porton Down,
      London, Hamburg, Marburg, Solna, Lyon and Rome, seeks to increase international
      collaboration in the areas of high containment laboratory biosafety and viral
      diagnostic capability, to strengthen Europe's capacity to respond to an
      infectious disease emergency, and to offer assistance to countries not equipped
      with such costly facilities. Network partners have agreed on a common strategy to
      fill the gaps identified in the field of risk group-4 agents' laboratory
      diagnosis, namely the lack of standardization and of reference samples. The
      network has received a further 3-year funding, to offer assistance to external
      laboratories, and to start the planning of field activities.

PMID- 19754730
TI  - Psychosocial consequences of infectious diseases.
AB  - Historically, there has been an exaggerated fear related to infection compared to
      other conditions. Infection possesses unique characteristics that account for
      this disproportionate degree of fear: it is transmitted rapidly and invisibly;
      historically, it has accounted for major morbidity and mortality; old forms re
      emerge and new forms emerge; and both the media and society are often in awe.
      Because, in an outbreak, the patient is both a victim and a vector, and because
      there exists the potential for infringement of personal rights in order to
      control an outbreak, infection may be viewed (and has been depicted in popular
      culture) as a foreign invasion. During recent outbreaks, fear, denial,
      stigmatization and loss have been recorded in the implicated individuals.
      Stigmatization and discrimination may further involve ethical correlations, and
      attempts to adress these issues through activism may also have unwarranted
      effects. Public health initiatives can address the public's fears by increasing
      health literacy, which can contribute to reducing stigmatization.

PMID- 19754732
TI  - Coexistence of lichen sclerosus with morphoea showing bilateral symmetry.

PMID- 19754733
TI  - Hyperpigmentation on the thumb with a clinical resemblance to malignant melanoma
      caused by chronic irritation due to sewing.

PMID- 19754734
TI  - Abstracts of the 13th Congress of the European Federation of Neurological
      Societies (EFNS). Florence, Italy. September 11-15, 2009.

PMID- 19754735
TI  - Drosomycin, an essential component of antifungal defence in Drosophila.
AB  - Drosomycin is an inducible antifungal peptide of 44 residues initially isolated
      from bacteria-challenged Drosophila melanogaster. The systemic expression of
      drosomycin is regulated by the Toll pathway present in fat body, whereas
      inducible local expression in the respiratory tract is controlled by the Immune
      Deficiency (IMD) pathway. Drosomycin belongs to the cysteine-stabilized alpha
      helical and beta-sheet (CSalphabeta) superfamily and is composed of an alpha
      helix and a three-stranded beta-sheet stabilized by four disulphide bridges.
      Drosomycin exhibits a narrow antimicrobial spectrum and is only active against
      some filamentous fungi. However, recent work using recombinant drosomycin
      expressed in Escherichia coli revealed its antiparasitic and anti-yeast
      activities. Two evolutionary epitopes (alpha- and gamma-patch) and the m-loop
      have been proposed as putative functional regions of drosomycin for interaction
      with fungi and parasites, respectively. Similarity in sequence, structure and
      biological activity suggests that drosomycin and some defensin molecules from
      plants and fungi could originate from a common ancestor.

PMID- 19754736
TI  - Evidence of multiple chromosomal inversions in Aedes aegypti formosus from
      Senegal.
AB  - Chromosomal inversions are prevalent in mosquito species but polytene chromosomes
      are difficult to prepare and visualize in members of the tribe Aedinii and thus
      there exists only indirect evidence of inversions. We constructed an F(1)
      intercross family using a P(1) female from a laboratory strain of Aedes aegypti
      aegypti (Aaa) and a P(1) male Aedes aegypti formosus (Aaf) from a strain
      collected from south-eastern Senegal. Recombination rates in the F(2) offspring
      were severely reduced and genotype ratios suggested a deleterious recessive
      allele on chromosome 3. The F(2) linkage map was incongruent in most respects
      with the established map for Aaa. Furthermore, no increased recombination was
      detected in F(5) offspring. Recombination rates and gene order were consistent
      with the presence in Aaf of at least four large inversions on chromosome 1, a
      single small inversion on chromosome 2 and three inversions on chromosome 3.

PMID- 19754737
TI  - Identification of pyrethroid resistance associated mutations in the para sodium
      channel of the two-spotted spider mite Tetranychus urticae (Acari:
      Tetranychidae).
AB  - We investigated pyrethroid resistance mechanisms in Tetranychus urticae strains
      from Greece. Combined bioassay, biochemical and synergistic data indicated that
      although P450 mono-oxygenase activities were associated with the trait, target
      site insensitivity was the major resistance component. A 3.3 kb cDNA fragment of
      the T. urticae para sodium channel gene encompassing segment 4 of domain II to
      segment 6 of domain IV was obtained by a degenerate PCR strategy. The T. urticae
      sequence showed highest identity (56%) to the scabies mite, Sarcoptes scabiei,
      and was phylogenetically classified within the divergent group of Arachnida.
      Comparison of resistant and susceptible strains identified the point mutation
      F1538I in segment 6 of domain III, which is known to confer strong resistance to
      pyrethroids, along with a second mutation (A1215D) in the intracellular linker
      connecting domains II and III with an unknown role. Three transcripts were
      identified corresponding to the k and l alternative exons. The mode of
      inheritance of resistance was confirmed as incompletely recessive, which is
      consistent with a target site mechanism for pyrethroids.

PMID- 19754738
TI  - Identification of a cis-regulatory element required for 20-hydroxyecdysone
      enhancement of antimicrobial peptide gene expression in Drosophila melanogaster.
AB  - The antimicrobial peptide diptericin plays an important role in defence against
      microorganisms. Drosophila melanogaster diptericin mRNA levels showed an increase
      during the late final instar larval stage when the ecdysteroid titres increase to
      initiate metamorphosis. Deletion analysis in Drosophila melanogaster mbn2 (mbn2)
      cells identified a cis-regulatory element (AAGAAAGATCCCCTG) necessary for 20
      hydroxyecdysone enhancement of peptidoglycan-induced expression of diptericin in
      the 3 kb diptericin promoter. Proteins extracted from mbn2 cells treated with
      peptidoglycan plus 20-hydroxyecdysone specifically bound to this element. 20
      hydroxyecdysone also enhanced peptidoglycan-induced expression of four other
      antimicrobial peptide (AMP) genes--drosomycin, attacin-A, metchnikowin and
      cecropin A1. Moreover, in silico promoter analysis using the meme program showed
      that an eight-nucleotide region of the identified cis-regulatory element is
      present in the promoters of these four AMP genes. These studies suggest that 20
      hydroxyecdysone regulates the expression of AMP genes through a conserved cis
      regulatory element.

PMID- 19754739
TI  - Annotation and analysis of low-complexity protein families of Anopheles gambiae
      that are associated with cuticle.
AB  - We have characterized four new families of homologous genes of the mosquito,
      Anopheles gambiae, all of which include members shown by previous work to be
      cuticular in nature. The CPLCG, CPLCW, CPLCP, and CPLCA families (where CPLC is
      'cuticular protein of low complexity') encode proteins with a high proportion of
      low-complexity sequence. We have also annotated the An. gambiae Tweedle genes, a
      family of cuticular protein genes first described in Drosophila, and additional
      ungrouped An. gambiae cuticular proteins identified by proteomics. Our
      annotations reveal multiple gene-family expansions that are specific to Diptera
      or Culicidae. The CPLCG and CPLCW families occur within a large and dynamic
      tandem array on chromosome 3R that includes sets of concertedly evolving genes.
      Most gene families exhibit two or more different expression profiles during
      development.

PMID- 19754740
TI  - Homing endonucleases catalyze double-stranded DNA breaks and somatic transgene
      excision in Aedes aegypti.
AB  - Aedes aegypti is a major vector of arthropod-borne viruses such as yellow fever
      virus and dengue viruses. Efforts to discern the function of genes involved in
      important behaviours, such as vector competence and host seeking through reverse
      genetics, would greatly benefit from the ability to generate targeted gene
      disruptions. Homing endonucleases are selfish elements which catalyze double
      stranded DNA (dsDNA) breaks in a sequence-specific manner. In this report we
      demonstrate that the homing endonucleases I-PpoI, I-SceI, I-CreI and I-AniI are
      all able to induce dsDNA breaks in adult female Ae. aegypti chromosomes as well
      as catalyze the somatic excision of a transgene. These experiments provide
      evidence that homing endonucleases can be used to manipulate the genome of this
      important disease vector.

PMID- 19754741
TI  - Changes in gene expression in the permissive larval host lightbrown apple moth
      (Epiphyas postvittana, Tortricidae) in response to EppoNPV (Baculoviridae)
      infection.
AB  - Host cell and virus gene expression were measured five days after per os
      inoculation of 3rd instar lightbrown apple moth (LBAM) larvae with the Epiphyas
      postvittana nucleopolyhedrovirus (EppoNPV). Microarray analysis identified 84
      insect genes that were up-regulated and 18 genes that were down-regulated in
      virus-infected larvae compared with uninfected larvae. From the 134 viral open
      reading frames represented on the microarray, 81 genes showed strong expression.
      Of the 38 functionally identifiable regulated insect genes, 23 coded for proteins
      that have roles in one of five processes; regulation of transcription and
      translation, induction of apoptosis, and maintenance of both juvenility and actin
      cytoskeletal integrity. Of the 34 functionally identifiable viral genes that were
      most strongly expressed, 12 had functions associated with these five processes,
      as did a further seven viral genes which were expressed at slightly lower levels.
      A survey of the LBAM-expressed sequence tag library identified further genes
      involved in these processes. In total, 135 insect genes and 38 viral genes were
      analysed by quantitative polymerase chain reaction. Twenty-one insect genes were
      strongly up-regulated and 31 genes strongly down-regulated. All 38 viral genes
      examined were highly expressed. These data suggest that induction of apoptosis
      and regulation of juvenility are the major 'battlegrounds' between virus and
      insect, with the majority of changes observed representing viral control of
      insect gene expression. Transcription and translational effects seem to be
      exerted largely through modulation of mRNA and protein degradation. Examples of
      attempts by the insect to repel the infection via changes in gene expression
      within these same processes were, however, also noted. The data also showed the
      extent to which viral transcription dominated in the infected insects at five
      days post inoculation.

PMID- 19754742
TI  - Shotgun proteomics approach to characterizing the embryonic proteome of the
      silkworm, Bombyx mori, at labrum appearance stage.
AB  - The shotgun approach has gained considerable acknowledgement in recent years as a
      dominant strategy in proteomics. We observed a dramatic increase of specific
      protein spots in two-dimensional electrophoresis (2-DE) gels of the silkworm
      (Bombyx mori) embryo at labrum appearance, a characteristic stage during
      embryonic development of silkworm which is involved with temperature increase by
      silkworm raiser. We employed shotgun liquid chromatography tandem mass
      spectrometry (LC-MS/MS) technology to analyse the proteome of B. mori embryos at
      this stage. A total of 2168 proteins were identified with an in-house database.
      Approximately 47% of them had isoelectric point (pI) values distributed
      theoretically in the range pI 5-7 and approximately 60% of them had molecular
      weights of 15-45 kDa. Furthermore, 111 proteins had an pI greater than 10 and
      were difficult to separate by 2-DE. Many important functional proteins related to
      embryonic development, stress response, DNA transcription/translation, cell
      growth, proliferation and differentiation, organogenesis and reproduction were
      identified. Among them proteins related to nervous system development were
      noticeable. All known heat shock proteins (HSPs) were detected in this
      developmental stage of B. mori embryo. In addition, Gene Ontology (GO) and Kyoto
      Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed energetic
      metabolism at this stage. These results were expected to provide more information
      for proteomic monitoring of the insect embryo and better understanding of the
      spatiotemporal expression of genes during embryonic developmental processes.

PMID- 19754743
TI  - Stability and loss of a virus resistance phenotype over time in transgenic
      mosquitoes harbouring an antiviral effector gene.
AB  - Transgenic Aedes aegypti were engineered to express a virus-derived, inverted
      repeat (IR) RNA in the mosquito midgut to trigger RNA interference (RNAi) and
      generate resistance to dengue virus type 2 (DENV2) in the vector. Here we
      characterize genotypic and phenotypic stabilities of one line, Carb77, between
      generations G(9) and G(17). The anti-DENV2 transgene was integrated at a single
      site within a noncoding region of the mosquito genome. The virus resistance
      phenotype was strong until G(13) and suppressed replication of different DENV2
      genotypes. From G(14)-G(17) the resistance phenotype to DENV2 became weaker and
      eventually was lost. Although the sequence of the transgene was not mutated,
      expression of the IR effector RNA was not detected and the Carb77 G(17)
      mosquitoes lost their ability to silence the DENV2 genome.

PMID- 19754744
TI  - A putative hexamerin from a Campodea sp. suggests an independent origin of
      haemocyanin-related storage proteins in Hexapoda.
AB  - Haemocyanins are copper-containing respiratory proteins in the arthropod
      haemolymph. In hexapods, haemocyanins gave rise to hexamerins, which have lost
      the ability to bind copper and thus oxygen. Hexamerins are thought to act mainly
      as storage proteins in nonfeeding periods. So far, hexamerins have only been
      identified in ectognathan hexapods, but not in Entognatha. Here we report the
      identification of a putative hexamerin from Campodea sp. (Diplura). The full
      length cDNA of Campodea sp. hexamerin 1 (CspHex1) measures 2188 bp and translates
      into a native polypeptide of 667 amino acids. As in other hexamerins, the six
      copper-coordinating histidines are not conserved. However, sequence comparison
      and phylogenetic analyses demonstrated that CspHex1 is not closely related to
      other hexapod hexamerins, which derive from hexapod type 1 haemocyanin subunits
      in the ectognathan lineage, but rather resembles a derivative of hexapod type 2
      haemocyanin subunits. Hence, haemocyanin-related storage proteins emerged at
      least two times independently in Hexapoda.

PMID- 19754745
TI  - Cloning and characterization of Dorsal homologues in the hemipteran Rhodnius
      prolixus.
AB  - Rhodnius prolixus is an ancient haematophagous hemipteran insect capable of
      mounting a powerful immune response. This response is transcriptionally regulated
      in part by transcription factors of the Rel/Nuclear Factor kappa B (Rel/NF
      kappaB) family. We have cloned and characterized three members of this
      transcription factor family in this insect. Dorsal 1A is primarily expressed in
      early developmental stages. In contrast, dorsal 1B and 1C, both differentially
      spliced products of dorsal 1A, are expressed primarily in the adult fat body in
      response to septic injury, suggesting their exclusive role in immunity.
      Additionally, we identified putative kappaB binding sites in the 5' upstream
      regions of target genes known to be involved in the innate immune response of
      insects.

PMID- 19754748
TI  - Zygomycosis comes of age. Proceedings of the 1st International Forum on
      Zygomycosis. May 30-June 1, 2008. Cape Sounion, Greece.

PMID- 19754747
TI  - Abstracts of the Forty-Ninth Annual Meeting of the Society for
      Psychophysiological Research. Berlin, Germany. October 21-24, 2009.

PMID- 19754749
TI  - The ecology of the Zygomycetes and its impact on environmental exposure.
AB  - Zygomycetes are unique among filamentous fungi in their great ability to infect a
      broader, more heterogeneous population of human hosts than other opportunistic
      moulds. Various members of the Zygomycetes have been implicated in zygomycosis,
      although those belonging to the family Mucoraceae are isolated more frequently
      than those of any other family. The environmental microbiology literature
      provides limited insights into how common zygomycetes are in the environment, and
      provides a few clues about which ecological niches these fungi are found in.
      Mucorales are thermotolerant moulds that are supposedly ubiquitous in nature and
      widely found on organic substrates, including bread, decaying fruits, vegetable
      matter, crop debris, soil between growing seasons, compost piles, and animal
      excreta. The scientific and medical literature does not support this
      generalization. Sporangiospores released by mucorales range from 3 to 11 microm
      in diameter, are easily aerosolized, and are readily dispersed throughout the
      environment. This is the major mode of transmission. However, there are very few
      data concerning the levels of zygomycete sporangiospores in outdoor and indoor
      air, especially in geographical areas where zygomycosis is particularly
      prevalent. Airborne fungal spores are almost ubiquitous and can be found on all
      human surfaces in contact with air, especially on the upper and lower airway
      mucosa. Inhalation of sporangiospores must be a daily occurrence. Surprisingly,
      members of the Mucorales are very rarely found in nasal mucus, suggesting that
      spores in the mucus of airway mucosa are cleared by mucociliary transport or that
      there is a low level of airborne contamination. Zygomycetes are found
      occasionally in water-damaged buildings, as demonstrated by air-sampling, and
      analysis of settled dust by quantitative PCR. Moreover, inhalation of
      sporangiospores in dust has been linked to outbreaks of rhinocerebral or
      pulmonary zygomycosis due to excavation, construction, or contaminated air
      conditioning filters. Whereas most zygomycete infections are community-acquired,
      nosocomial acquisition due to percutaneous routes of exposure is very important.
      Sporadic cases, and pseudo-outbreaks, have been linked to contaminated bandages
      and adhesive dressings, needles, and tongue depressors used to construct splints
      for intravenous and arterial cannulation sites in preterm infants. Insect bites
      or stings have been implicated in disease transmission in cases of cutaneous and
      subcutaneous zygomycosis, e.g. diseases caused by the Entomophthorales. Traumatic
      implantation of spores in dirt or in contaminated water, e.g. as occurred during
      the Asian tsunami, has led to infection in multiple patients.

PMID- 19754750
TI  - Changing epidemiology of an emerging infection: zygomycosis.
AB  - Aspergillosis and candidosis remain the most prevalent opportunistic fungal
      infections in immunocompromised patients, but diseases caused by the Zygomycetes
      have become of increasing importance. Exposure to antimycotic drugs with no
      activity against zygomycetes may be a new risk factor and an explanation for the
      increasing incidence of zygomycosis. The latter infection occurs only rarely in
      immunocompetent hosts, but in recent years Apophysomyces elegans has been
      described in many subtropical countries as an emerging pathogen causing mostly
      cutaneous infections after traumatic inoculation.

PMID- 19754751
TI  - Clinical presentation of zygomycosis.
AB  - Zygomycetes are filamentous fungi with a worldwide distribution. This class of
      fungi encompasses two orders, i.e. the Mucorales and the Entomophthorales.
      Members of the latter are associated with chronic cutaneous and subcutaneous
      infections that are limited to the tropics and rarely disseminate to internal
      organs. The order Mucorales includes several species involved in rhinocerebral,
      pulmonary, cutaneous, gastrointestinal and other less frequent infections in
      immunocompetent and immunocompromised individuals, and is characterized by a
      tendency to disseminate. Portals of entry of zygomycetes are usually the lungs,
      skin, and gastrointestinal tract. A characteristic property of zygomycetes is
      their tendency to invade blood vessels and to cause thrombosis-processes that
      result in subsequent necrosis of involved tissues. Risk factors associated with
      zygomycosis include prolonged neutropenia and use of corticosteroids, solid organ
      or haematopoietic stem cell transplantation, AIDS, poorly controlled diabetes
      mellitus, iron chelation with deferoxamine, burns, wounds, malnutrition, extremes
      of age, and intravenous drug abuse. Recently, the widespread use of voriconazole
      for prophylaxis or treatment of aspergillosis in patients with haematological
      malignancies has been linked with a rise in the numbers of cases of invasive
      zygomycosis. As the symptoms, clinical signs and imaging findings of these
      infections are non-specific, a high index of suspicion is required for timely
      diagnosis. Early diagnosis, correction of the underlying predisposing factors,
      aggressive surgical debridement of all infected tissues and lengthy
      administration of antifungals are the only potentially curative options for this
      rare but emerging invasive fungal infection.

PMID- 19754752
TI  - Zygomycosis and diabetes mellitus.
AB  - Zygomycoses are severe angio-invasive fungal infections that develop in
      immunocompromised and diabetic patients. Any episode of sinusitis not responding
      to short-term antibacterial therapy should evoke the diagnosis of zygomycosis in
      the latter population, especially in cases of a surrounding necrotic area.
      Appropriate diagnosis is obtained after careful direct examination of the sample
      and culture. Current therapy underscores the need to control glycaemia and
      acidosis in addition to the need for urgent administration of high-dose liposomal
      amphotericin B in combination with extensive surgery.

PMID- 19754753
TI  - The role of iron and iron chelators in zygomycosis.
AB  - Iron is an essential element for cell growth and development, contributing to DNA
      synthesis and regulating the G(1)-phase to S-phase transition. Moreover, iron is
      important for the virulence of the majority of microorganisms, and the function
      of the genes regulating iron uptake is coupled with the manifestations of the
      virulence phenotype. All fungi elaborate specific uptake mechanisms to sequester
      iron, and most commonly produce small molecules with high affinity for iron, the
      siderophores. The importance of iron appears to be particularly high for
      Zygomycetes, which grow abundantly in iron-rich media, and all the known
      predisposing factors for zygomycosis have, as a common feature, the increased
      availability of free iron. Among the known iron chelators, deferoxamine supports
      the growth of Zygomycetes because it acts as xenosiderophore, delivering iron to
      iron-uptaking molecules of these species. Conversely, the newer iron chelators
      deferiprone and deferasirox do not exhibit similar activity, apparently because
      they share higher affinity constants for iron and, as a result, deprive the fungi
      of iron, inhibiting their growth. This activity has been documented in various
      culture systems and in many animal models of zygomycosis, and therefore suggests
      that these drugs might be used as adjuvant treatment for systemic zygomycosis.
      There are few case reports in which the newer iron chelators have been used as
      antifungals, and their possible benefit must be verified in a prospective
      randomized trial.

PMID- 19754754
TI  - The role of neutrophils in the development and outcome of zygomycosis in
      haematological patients.
AB  - Zygomycosis constitutes the third leading cause of invasive fungal infections
      following aspergillosis and candidosis. Patients with haematologic malignancies
      or haematopoietic stem cell transplantation are particularly susceptible to
      zygomycosis. Neutropenia represents the most important pathogenic mechanism
      influencing the onset and outcome of zygomycosis. Neutrophils cause a lesion of
      the fungal wall with subsequent destruction by macrophages. They also enhance the
      activity of antifungal drugs against Zygomycetes. Strategies that aim to increase
      neutrophil count and function, such as granulocyte colony stimulating factor and
      granulocyte transfusion, could play an important role in the management of this
      life-threatening infectious complication.

PMID- 19754755
TI  - Incidence of zygomycosis in transplant recipients.
AB  - Recently, a remarkable increase in the incidence of zygomycosis has been reported
      from institutions in the USA and Europe. The use of voriconazole for the
      treatment of aspergillosis and, less frequently, the use of echinocandins as
      empirical treatment for invasive fungal infections are thought to be responsible
      for the increase. In addition, an increased incidence of this infection has been
      observed in transplant recipients, including both haematopoietic stem cell
      transplant (HSCT) and solid organ transplant (SOT) patients. There are no global
      surveys on the prevalence or incidence of zygomycosis, but data from individual
      institutions and countries show that zygomycosis is an emerging infection. The
      increased incidence of zygomycosis most probably reflects a greater frequency of
      predisposing factors, such as higher numbers of patients undergoing HSCT and
      immunosuppressive chemotherapy. In addition, the emergence of rare pathogens as a
      result of the rise in the use of antifungal therapy against common species can be
      postulated. Further, the availability of antifungal agents with activity profiles
      that are more specific for selected fungi increases the necessity of identifying
      pathogenic fungi; the frequency of Zygomycetes infections may have been
      underestimated until now because therapeutic decisions did not depend on the
      precise identification of pathogenic fungi.

PMID- 19754756
TI  - Cutaneous zygomycosis.
AB  - The prevalence of cutaneous and soft tissue zygomycosis appears to have increased
      in recent years. We reviewed 78 case reports of cutaneous zygomycosis published
      from 2004 through 2008. Most patients with cutaneous zygomycosis have underlying
      conditions such as haematological malignancies, diabetes mellitus or solid organ
      transplantation, but a large proportion of them are immunocompetent. Trauma is
      the most common predisposing factor leading to zygomycosis in immunocompetent
      patients. If the patient is immunocompromised, the infection may disseminate.
      Cutaneous zygomycosis may be localized, may extend to deep underlying tissues, or
      may be disseminated. The most common clinical presentation is induration of the
      skin with surrounding erythema, rapidly progressing to necrosis. Histological
      examination and culture of soft tissue are important for the diagnosis of
      cutaneous zygomycosis. Treatment consists of surgical debridement, administration
      of antifungal agents (amphotericin B formulations and/or posaconazole) and,
      occasionally, hyperbaric oxygen. Mortality rates are approximately 30%.

PMID- 19754757
TI  - Disseminated zygomycosis with involvement of the central nervous system.
AB  - Zygomycosis of the central nervous system (CNS) can manifest in three distinct
      clinical forms, as rhinocerebral zygomycosis, as disseminated zygomycosis with
      CNS involvement, and as isolated cerebral zygomycosis. We present a case of a 2
      year-old boy with leukaemia and disseminated zygomycosis, caused by Absidia
      corymbifera, involving the brain, spinal cord, lung and liver. The child received
      treatment with liposomal amphotericin B and posaconazole for 6 months. Although
      the lesions of the lungs and liver resolved, those of the CNS persisted and the
      child is in a vegetative state. A review of the literature after 2004 identified
      ten additional cases of disseminated zygomycosis with cerebral involvement, all
      but one of which had concurrent lung infection. The most common underlying
      disease in these cases was haematological malignancy and the mortality rate was
      70%. Disseminated zygomycosis with cerebral involvement is a fatal disease. Early
      recognition and prompt intervention with combined medical and surgical treatment
      may improve the outcome.

PMID- 19754758
TI  - Invasive zygomycosis in neonates and children.
AB  - Invasive zygomycosis in neonates and children has both similarities to and
      differences from that in adults. We searched PubMed and individual references for
      English-language reports of single cases or case series of neonatal (<1 month)
      and paediatric (< or =18 years) zygomycosis and compared the results with
      published results in adults. Cases were included if they fulfilled pre-specified
      criteria. A total of 59 cases of neonatal zygomycosis were reported to July 2007;
      157 paediatric cases were published up to 2004 and an additional 30 paediatric
      cases were reported more recently. Prematurity was a major underlying factor
      among neonatal cases. The most common manifestations of zygomycosis were
      gastrointestinal (54%) and cutaneous (36%). This pattern differs from the
      sinopulmonary and rhinocerebral patterns typical in older children and adults.
      Overall mortality was 64% in neonates, 56% in children and 53% in adults. A
      tendency for dissemination was higher in neonates than adults. Dissemination and
      young age (<1 year) were independent risk factors for death in children. Most
      patients who survived received antifungal therapy. Surgery combined with
      antifungal therapy was a protective factor against death. Most neonates and
      children who survived had received an amphotericin B formulation. Zygomycosis is
      a life-threatening infection in children and neonates with differing patterns of
      involvement in individuals of different ages. The most common management strategy
      in survivors involved a combination of amphotericin B and surgery.

PMID- 19754759
TI  - Outbreaks of zygomycosis in hospitals.
AB  - Zygomycosis refers to a group of uncommon and frequently fatal mycoses caused by
      fungi of the class Zygomycetes, the organisms of which are usually found in
      decaying organic matter. Disease can be transmitted by the inhalation of spores
      or by direct inoculation on disrupted skin or mucosa. For rare diseases such as
      zygomycosis, two or more cases occurring in a short time should be investigated
      as a probable epidemic. Twelve hospital outbreaks and two pseudoepidemics caused
      by Zygomycetes have been cited in the English literature. The first epidemic was
      recorded in 1977 and the last in 2008. Outbreaks have been reported in the USA,
      the UK and elsewhere in Europe. Cases have included cutaneous, disseminated,
      pulmonary and rhinocerebral disease. Species identified have included Rhizopus
      arrhizus, Rhizopus rhizopodiformis, Rhizopus microsporus, Rhizopus spp., Absidia
      corymbifera and Rhizomucor pusillius. Sources of infection have included
      Elastoplast adhesive bandage rolls, ventilation systems, wooden tongue
      depressors, karaya (plant-derived adhesive) ostomy bags, and water damage to a
      linen store and patient shower room. Patients have included cardiosurgery
      patients, renal transplant recipients, orthopaedic patients, adult leukaemia
      patients, intensive care unit neonates, immunocompromised haematology patients,
      and burn unit patients. Although zygomycosis outbreaks in the hospital
      environment are infrequent, a high index of suspicion should exist if necrotic
      lesions appear in proximity to a postoperative wound. Direct tissue examination
      and tissue culture and histopathology must be routinely performed.

PMID- 19754760
TI  - Zygomycosis: conventional laboratory diagnosis.
AB  - A definitive diagnosis of zygomycosis caused by Mucorales can be made by
      histopathological examination with or without isolation of the fungus from the
      same site. Histopathological examination of the tissues affected typically shows
      characteristic broad, hyaline, ribbon-like, irregular fungal hyphae with wide
      angle branching, accompanied by tissue necrosis and angioinvasion of the fungi.
      Tissue invasion by the fungal hyphae as seen by microscopy is essential to
      establish the diagnosis. Fungal elements can be stained with Gomori methenamine
      silver, periodic acid-Schiff or Calcoflour white stain. All Mucorales grow
      rapidly on most fungal media such as Sabouraud dextrose agar incubated at 25-30
      degrees C. Mucorales from a sterile site or repeated positive cultures of the
      fungi from a non-sterile site are considered significant in a high-risk patient
      with predisposing factors for acquisition of zygomycosis. Positive cultures from
      non-sterile specimens should be interpreted with caution and will require
      correlation between the finding and the clinical situation.

PMID- 19754761
TI  - Molecular tools for identification of Zygomycetes and the diagnosis of
      zygomycosis.
AB  - The identification of Zygomycetes and diagnosis of zygomycosis are notoriously
      difficult. However, there have been recent advances, particularly in the
      availability and evaluation of new molecular approaches. Two main issues are of
      importance: the identification to species level of a strain isolated in culture,
      and the identification of a zygomycete in tissues. By using several molecular
      targets and by increasing the number of available DNA sequences in international
      databases, several studies have shown that accurate molecular identification of
      Zygomycetes to species level is feasible. The internal transcribed spacer (ITS)
      region may be used as a first-line molecular target for the identification of
      Zygomycetes in pure culture. However, cultures from infected tissues are often
      negative and the different Zygomycetes share similar morphology according to
      histopathology. Furthermore, differentiation of a zygomycete from another
      hyalohyphomycete can sometimes be difficult in histopathology. Thus, alternative
      methods for the diagnosis of zygomycosis and for species identification directly
      from tissues are needed. For this purpose, molecular methods have been recently
      evaluated, both on unfixed fresh/frozen material and on formalin-fixed, paraffin
      embedded biopsies. This review discusses the molecular approaches currently
      available for the identification of Zygomycetes and the diagnosis of zygomycosis.

PMID- 19754762
TI  - In vitro activity of antifungals against Zygomycetes.
AB  - To date, no reference standard for therapy for zygomycosis has been established
      because there are insufficient clinical data with which to make such a judgement.
      Knowledge of the species responsible for the infection and its antifungal
      susceptibility profile has become increasingly important in the management of
      patients. Amphotericin B is the most active drug against all the species
      involved, followed by posaconazole, whereas voriconazole has no activity.
      Echinocandins are completely inactive in vitro, but may be an interesting option
      when used in combination with other drugs.

PMID- 19754763
TI  - Current experience in treating invasive zygomycosis with posaconazole.
AB  - The treatment of zygomycosis has two cornerstones, namely, surgery and antifungal
      drugs. In many patients, both need to be applied to achieve treatment success;
      without treatment, the mortality rate of zygomycosis approaches 100%. Because
      treatment options are limited, no well-designed randomized clinical trial has
      been conducted and data are predominantly derived from compassionate-use
      programmes or case reports. Amphotericin B (AmB) lipid complex (ABLC) was
      clinically evaluated for efficacy against zygomycosis in a single series and
      resulted in cure or improvement in 52% and in the stabilizing of disease in 20%
      of patients. Liposomal AmB (L-AmB) is frequently used, but no large series have
      yet been published. Posaconazole has demonstrated in vitro and in vivo activity
      against Zygomycetes. Two series demonstrated salvage treatment response rates of
      60% and 79%, respectively. Antifungal combinations have not been evaluated
      thoroughly enough to warrant recommendations outside of clinical trials. Survival
      is usually associated with surgical debridement and improvement in underlying
      diseases. Currently, surgical debridement should be performed. Antifungal
      treatment should consist of either ABLC > or =5 mg/kg once per day or L-AmB > or
      =3 mg/kg once per day. When toxicity occurs or stable fungal disease is achieved,
      treatment can be switched to oral posaconazole 200 mg four times per day. If
      impaired kidney function is overt or expected on the grounds of, for example,
      uncontrolled diabetes, primary treatment of zygomycosis with posaconazole is an
      option.

PMID- 19754764
TI  - Hyperbaric oxygen therapy and other adjunctive treatments for zygomycosis.
AB  - Zygomycetes are increasingly reported as a cause of life-threatening invasive
      fungal infections in profoundly immunocompromised patients and in those with
      diabetic ketoacidosis. Zygomycosis, typically presents as soft tissue, rhino
      orbitocerebral, pulmonary or disseminated disease and is characterized by rapid
      clinical progression and high mortality rates. Treatment with amphotericin B
      lipid formulations in combination with surgery and, perhaps, the addition of
      caspofungin offers the best chance for survival; posaconazole, a new antifungal
      triazole, is increasingly used for consolidation or maintenance therapy. Because
      of the poor prognosis of zygomycosis, particularly in immunocompromised cancer
      patients, adjunctive treatments such as hyperbaric oxygen therapy, use of
      immunomodulatory cytokines, and in vivo iron starvation continue to be explored.
      However, although each of these modalities is based on a plausible scientific
      rationale and has been helpful in the management of individual patients, there is
      no clinical evidence for their general effectiveness as adjunctive treatments in
      patients with zygomycosis. Further experimental and clinical investigations are
      necessary to determine whether and how these treatments can impact on outcome and
      to determine which patients and which types of infection may benefit from them.

PMID- 19754765
TI  - Lipid formulations of amphotericin B as first-line treatment of zygomycosis.
AB  - Zygomycosis is a difficult to treat and frequently fatal infection affecting
      immunocompromised and, rarely, immunocompetent patients. The early diagnosis and
      immediate initiation of treatment with an antifungal agent in combination with
      surgical intervention has proved critical for the favourable outcome of the
      disease. Few antifungal agents are available for treatment. Amphotericin B (AmB)
      deoxycholate has been the drug of choice for many years and is usually given at
      high daily doses which can result in renal toxicity. Currently, lipid
      formulations of AmB (liposomal AmB (L-AmB), AmB lipid complex (ABLC), AmB
      colloidal dispersion (ABCD)), mainly L-AmB, rather than conventional AmB have
      become the standard therapy. The rationale behind the use of lipid formulations
      is that they decrease the nephrotoxicity associated with longterm AmB use.
      Although there is a developing consensus that high doses of lipid formulations of
      AmB should be the antifungal therapy of choice for all patients with zygomycosis,
      until now there have been no data available with which to define the appropriate
      dose. The duration of therapy remains an unresolved issue, regarding both lipid
      formulations of AmB as well as sequential or combination treatments consisting of
      lipid formulations of AmB with posaconazole, a drug which has now emerged as a
      new therapeutic option.

PMID- 19754766
TI  - Voriconazole-associated zygomycosis: a significant consequence of evolving
      antifungal prophylaxis and immunosuppression practices?
AB  - Mucormycosis (zygomycosis) is an uncommon infection that afflicts severely
      immunocompromised patients and those with poorly controlled diabetes mellitus. A
      recent increase in the incidence of mucormycosis at many transplant centres has
      been linked to the introduction and widespread use of voriconazole prophylaxis in
      these high-risk populations. However, it is not known if this association
      reflects a true epidemiological link or represents a marker of changing
      immunosuppression occurring in parallel with the evolution of transplant
      practices and immunosuppression strategies.

PMID- 19754767
TI  - Orbitomaxillary mucormycosis (zygomycosis) and the surgical approach to
      treatment: perspectives from a maxillofacial surgeon.
AB  - Rhinocerebral or rhino-orbitocerebral (mucormycosis) zygomycosis (ROCZ) usually
      occurs among patients with poorly controlled diabetes mellitus (especially those
      with ketoacidosis), solid malignancies, iron overload or extensive burns, in
      patients undergoing treatment with glucocorticosteroid agents, or in patients
      with neutropenia related to haematologic malignancies. The disease process starts
      with inhalation of the fungus into the paranasal sinuses. The fungus may spread
      to invade the palate, sphenoid sinus, cavernous sinus, orbits or cranially to
      invade the brain. Pain and swelling precede oral ulceration and the resulting
      tissue necrosis can result in palatal perforation. Infection can sometimes extend
      from the sinuses into the mouth and produce painful, necrotic ulcerations of the
      hard palate. If untreated, infection usually spreads from the ethmoid sinus to
      the orbit, resulting in the loss of extraocular muscle function and proptosis.
      Surgical treatment includes the resection of involved tissues of the face,
      including skin and muscle, any skin of the nose that is involved, maxillary and
      ethmoid sinuses, necrotic tissue of the temporal area and infratemporal fossa,
      and orbital exenteration. The keys to successful therapy include suspicion of the
      diagnosis and early recognition of the signs and symptoms, correction of
      underlying medical disorders such as ketoacidosis, and aggressive medical and
      surgical intervention.

PMID- 19754768
TI  - Angiogenesis and cerebral neoplasia.
AB  - Angiogenesis is a fundamental process in reproduction and wound healing. It is a
      tightly regulated process causing neovascularization. However, if angiogenesis
      becomes unregulated, it may be responsible for several disease processes such as
      brain tumour growth and metastasis. An understanding of the factors implicated in
      angiogenesis and its inhibition is essential if they are to be exploited as
      possible clinical treatments for brain tumours. Unfortunately, there are multiple
      factors known to be involved in the regulation of angiogenesis, and hence, the
      clinical application of any single agent may not be effective. This article
      summarizes the processes of blood vessel formation in the brain, examines the
      angiogenic factors that are important in the nervous system and discusses their
      role in brain tumour development and possible treatment.

PMID- 19754769
TI  - A case of bilateral renal lymphosarcoma with secondary polycythaemia and
      paraneoplastic syndromes of hypoglycaemia and uveitis in an English Springer
      Spaniel.
AB  - Primary renal lymphosarcoma in dogs has rarely been reported. Controversy exists
      whether it is a primary neoplasm of the kidney or a metastatic neoplasm. The case
      described is the first reported case of treatment with chemotherapy for a dog
      with renal lymphosarcoma.

PMID- 19754770
TI  - Pancreatic mixed acinar-endocrine carcinoma in a dog.
AB  - A 10.5-year-old crossbreed dog was presented with a history of hypoglycaemic
      episodes and elevated serum insulin concentration. A pancreatic mass was removed
      at surgery along with an enlarged draining lymph node. An unresectable hepatic
      nodule was also present. Immunohistochemistry confirmed the pancreatic and lymph
      node masses as functional mixed acinar-endocrine carcinoma, previously unreported
      in domestic species. Persistent hypoglycaemia and hyperinsulinaemia post
      operatively was highly suggestive of the hepatic mass being a functional
      metastasis. The dog was managed on prednisolone and remained asymptomatic 9
      months post-operatively. This tumour type has only been rarely reported in human
      patients and may highlight the need for more rigorous immunohistochemical
      staining of pancreatic masses in veterinary species to identify the prevalence of
      this tumour type.

PMID- 19754772
TI  - Evaluation of intracavitary mitoxantrone and carboplatin for treatment of
      carcinomatosis, sarcomatosis and mesothelioma, with or without malignant
      effusions: A retrospective analysis of 12 cases (1997-2002)*.
AB  - Abstract Carcinomatosis, sarcomatosis and mesothelioma, with or without malignant
      effusions, are difficult to treat and generally carry a poor prognosis. The
      purpose of this study was two-fold; first, to determine the prognosis for dogs
      with carcinomatosis, sarcomatosis, or mesothelioma, with or without malignant
      effusions; second, to evaluate the safety and efficacy of treatment with
      intracavitary (IC) carboplatin and mitoxantrone in dogs with these syndromes.
      Nineteen dogs were evaluated. Seven were untreated and 12 were treated with IC
      chemotherapy (mitoxantrone and/or carboplatin), and multiple factors were
      analysed for significance with respect to survival time. The median survival time
      (MST) for untreated dogs was 25 days, whereas the MST for treated dogs was 332
      days (Log Rank, P < 0.0001). Treatment with IC chemotherapy was well tolerated.
      This study suggests that IC chemotherapy with mitoxantrone and/or carboplatin is
      an effective treatment for dogs with carcinomatosis, sarcomatosis or
      mesothelioma, with or without malignant effusion.

PMID- 19754773
TI  - Vascular-targeted photodynamic therapy (VTP) of a canine-transmissible venereal
      tumour in a murine model with Pd-bacteriopheophorbide (WST09).
AB  - Abstract Treatment of canine-transmissible venereal tumour (CTVT) with local
      vascular-targeted photodynamic therapy (VTP) using Pd-bacteriopheophorbide
      (WST09) as a drug is suggested as an alternative to conventional chemotherapy.
      Male CD1 nude mice were subcutaneously grafted with the xenograft-transmissible
      canine venereal tumour (XTVT). The VTP protocol delivered once consisted of
      intravenous administration of WST09 (10 mg kg(-1)) followed by immediate local
      illumination with a diode laser (763 nm). Controls included animals treated with
      light or WST09 alone. Macroscopic and microscopic evaluations of tumour response
      were conducted 10, 24 and 48 h after treatment. Upon VTP, tumours underwent
      necrosis that lasted 8-10 days and exhibited complete healing by 25-35 days,
      reaching an overall long-term cure rate (83%) by 90 days after treatment. This
      study suggests that VTP with WST09 can efficiently treat CTVT in a single
      session, as compared with 4-6 sessions of chemotherapy and thus may be feasible
      for common veterinary practice, particularly under ambulatory conditions.

PMID- 19754774
TI  - Pituitary-adrenal axis function in dogs with neoplasia*.
AB  - Abstract Adrenocorticotropic hormone (ACTH) stimulation tests were done in
      healthy and tumour-bearing dogs. In the tumour-bearing dogs, plasma endogenous
      ACTH (eACTH) concentration was measured and adrenal gland size was assessed
      ultrasonographically. Measurements in the tumour-bearing dogs were taken prior to
      therapy. No difference existed in basal or ACTH-stimulated cortisol concentration
      between tumour-bearing and healthy dogs. No difference existed in eACTH
      concentration between dogs with non-haematopoietic neoplasia (NHN) and lymphoma.
      However, of 20 dogs with lymphoma, 15% had increased basal serum cortisol
      concentration, 5% had an exaggerated response to ACTH and 5% had an increased
      eACTH concentration. Of 15 dogs with NHN, 20% had increased basal cortisol
      concentration, 7% had an exaggerated ACTH response and no dogs had an increased
      eACTH concentration. Of the dogs with lymphoma and NHN, 5 and 13%, respectively,
      had decreased basal cortisol concentrations; 20% of dogs with lymphoma and 13%
      with NHN had a subnormal ACTH response. eACTH levels were below the reference
      range in 10% of dogs with lymphoma and 7% with NHN. Overall, 10 adrenal glands
      were enlarged in seven dogs, five with lymphoma and two with NHN. The clinical
      significance of these findings remains to be determined.

PMID- 19754775
TI  - Detection of centrosome amplification as a surrogate marker of dysfunction in the
      p53 pathway -p53 gene mutation or MDM2 overexpression.
AB  - Abstract In human and canine cancers, the inactivation of p53 protein as well as
      p53 gene mutation and MDM2 overexpression result in centrosome amplification that
      in turn contributes to chromosomal instability. To explore the usefulness of the
      detection of centrosome amplification as a surrogate marker of dysfunction in the
      p53 pathway, we systematically analysed centrosome amplification, p53
      overexpression, p53 gene mutation and MDM2 overexpression in canine tumours.
      Centrosome amplification was detected in 16 of 51 (31%) naturally developing
      tumours in dogs. All the tumour specimens with aberrations in the p53 pathway,
      including p53 overexpression, p53 gene mutation or MDM2 overexpression, showed
      centrosome amplification, suggesting that the detection of centrosome
      amplification could serve as a preliminary surrogate marker of dysfunction in the
      p53 pathway.

PMID- 19754776
TI  - Measurements of hypoxia ([(18)F]-FMISO, [(18)F]-EF5) with positron emission
      tomography (PET) and perfusion using PET ([(15)O]-H(2)O) and power Doppler
      ultrasonography in feline fibrosarcomas*.
AB  - Abstract The aim of this study was to evaluate if hypoxia in feline fibrosarcomas
      can be detected. This was done using positron emission tomography (PET), two
      hypoxia tracers and polarographic pO(2) measurements. Of the seven cats included,
      five received [(18)F]-fluoromisonidazole and two 2-(2-nitro-1H-imidazol-1-yl)-N
      (2,2,3,3,3-pentafluoropropyl) acetamide. Perfusion was evaluated with [(15)O]
      H(2)O (n = 4) and with contrast-enhanced power Doppler ultrasonography (n = 5).
      Hypoxia was detected in three cats. Polarographic pO(2) measurements did not
      confirm PET results. In the ultrasonographic evaluation, low vascularity and low
      perfusion were seen with a peripheral vascular pattern and no perfusion in the
      centre of the tumour. This was in contrast to the [(15)O]-H(2)O scans, where
      central perfusion of the tumour was also found. In conclusion, it appears that
      hypoxia exists in this tumour type. The presence of tumour necrosis and
      heterogeneous hypoxia patterns in these tumours may explain the found
      discrepancies between the applied techniques.

PMID- 19754777
TI  - Oral malignant melanoma - the effect of coarse fractionation radiotherapy alone
      or with adjuvant carboplatin therapy.
AB  - Abstract A retrospective study was undertaken of dogs presented to the Animal
      Health Trust for treatment of oral malignant melanoma, without radiographic
      evidence of pulmonary metastases. Group 1 (n = 13) received radiotherapy of the
      primary and any lymph node metastases (4 weekly fractions of 9 Gy); and group 2
      (n = 15) were treated the same but additionally received between two and six
      doses carboplatin at 300 mg m(-2) every 3 weeks. Median survival times for the
      two groups were 307 and 286 days, respectively (P > 0.05). In addition,
      carboplatin therapy did not significantly reduce the proportion of dogs dying due
      to metastases (three from group 1 and four from group 2). We found no evidence of
      a beneficial effect of carboplatin therapy over radiotherapy alone.

PMID- 19754778
TI  - Canine acute radiation dermatitis, a survey of current management practices in
      North America.
AB  - Acute radiation-induced dermatitis (ARID) is a common sequela of radiation
      therapy in dogs. There is no consensus regarding ARID management in human
      medicine and the standard of care in veterinary medicine has not been reported.
      The objective was to report the practice standards for ARID management in dogs in
      North America. The design used was a questionnaire survey. Fifty-eight private
      and university teaching veterinary hospitals were contacted, 54 participated. The
      topical and oral medications used to treat ARID, prevent or treat bacterial
      infection, control pain and the indications for and timing of treatment
      initiation were the outcome measures. A minority of facilities (4/54, 7.5%) use
      exactly the same protocol regarding all parameters. There was agreement (>75% of
      facilities) with respect to the general use of oral antibiotics (77.8%), the need
      for pain control (92.6%) and the use of tramadol for pain control (76%), although
      the details of their use varied widely. There is a divergence of opinions
      regarding all details of ARID management in dogs except the general use of oral
      antibiotics and pain control medications.

PMID- 19754779
TI  - Expression of vascular endothelial growth factor in canine oral malignant
      melanoma.
AB  - Serum, plasma and tissue expression of vascular endothelial growth factor (VEGF)
      was measured in 20 dogs previously diagnosed histologically with oral melanoma.
      The concentrations of VEGF in serum and plasma were significantly higher in dogs
      with melanoma than in a control population (P <or= 0.002). Concentrations of VEGF
      in the serum and plasma of dogs with melanoma were highly correlated (r = 0.867).
      Ninety-five per cent of melanoma tissues expressed VEGF. Two staining patterns
      were detected: diffuse and granular cytoplasmic staining. High blood
      concentrations of VEGF were correlated to a shorter survival time in dogs
      receiving definitive therapy (P = 0.002). Survival times were significantly
      longer in dogs receiving definitive therapy versus palliative therapy (median 496
      versus 97 days, P = 0.007). Blood concentrations of VEGF were associated with
      stage (P < 0.05). Dogs with oral melanoma have increased serum, plasma and tissue
      concentrations of VEGF. Increased expression of VEGF may be a reasonable target
      for future therapy of canine oral melanoma.

PMID- 19754780
TI  - Human granulocyte-macrophage colony-stimulating factor DNA cationic-lipid
      complexed autologous tumour cell vaccination in the treatment of canine B-cell
      multicentric lymphoma.
AB  - This study describes the development of an human granulocyte-macrophage colony
      stimulating factor DNA cationic-lipid complexed autologous tumour cell vaccine
      (hGM-CSF CLDC ATCV) and its implementation, following a chemotherapy treatment
      protocol, in a randomized, placebo-controlled, double-blinded clinical trial in
      pet dogs with naturally occurring lymphoma. We hypothesized that the use of this
      vaccine would result in an antitumour immune response leading to improved first
      remission duration and overall survival in dogs with B-cell lymphoma when
      compared with chemotherapy alone. Immune stimulation generated by hGM-CSF CLDC
      ATCV was assessed by means of surrogate in vivo analysis (delayed-type
      hypersensitivity [DTH]) as well as an ex vivo cellular assay (lymphocyte
      proliferation assay). The vaccine approach considered in the current report did
      not result in clinically improved outcomes. A small measure of immunomodulation
      was documented by DTH and several modifications to the approach are suggested.
      This report illustrates the feasibility of clinical trials with vaccine
      strategies using companion animals with non-Hodgkin's lymphoma.

PMID- 19754781
TI  - Expression of E-cadherin in canine anal sac gland carcinoma and its association
      with survival.
AB  - The objective of this study was to determine whether an association could be
      demonstrated between survival and the expression of the adhesion molecule E
      cadherin by the neoplastic cells in a group of dogs with anal sac gland
      carcinomas (ASGCs). Archived formalin-fixed, paraffin wax-embedded primary tumour
      specimens were obtained for 36 cases of canine ASGC with known clinical
      management and survival data. Immunohistochemical methods were used to evaluate E
      cadherin expression by the neoplastic cells and data were evaluated for an
      association between E-cadherin expression and survival. On univariate analysis,
      the median survival time for cases with tumours expressing E-cadherin in more
      than 75% of cells was significantly greater than that for cases with tumours
      expressing E-cadherin in fewer than 75% of cells (1168 versus 448 days, P =
      0.0246). Both E-cadherin expression and presence or absence of distant metastases
      were significantly associated with survival on multivariate analysis. This study
      demonstrates that expression of E-cadherin at the cytoplasmic membrane in canine
      ASGCs is variable and potentially predictive of survival.

PMID- 19754782
TI  - Postsurgical intra-incisional 5-fluorouracil in dogs with incompletely resected,
      extremity malignant spindle cell tumours: a pilot study.
AB  - The safety and efficacy of intra-incisional 5-fluorouracil (5-FU) in the
      management of incompletely resected malignant spindle cell tumours of extremities
      was evaluated in six dogs. After marginal surgery, the dogs underwent weekly
      intra-incisional 5-FU for a minimum of six cycles. Treatment was well tolerated
      by all dogs, with no systemic adverse effects and only one episode of local
      cutaneous hyperpigmentation, which completely and spontaneously resolved. Median
      follow-up for all the dogs was 546 days (mean 619; range 297-1207). At the date
      of analysis, four dogs were still alive with no evidence of local recurrence, and
      two dogs had died as a result of their disease. The cause of death was
      development of distant metastases in one dog and tumour regrowth in the other.
      Despite the small sample size, this study documents that intra-incisional 5-FU
      chemotherapy is a safe and efficacious adjuvant treatment in the case of
      incompletely resected malignant spindle cell tumours in dogs and that long
      disease control can be achieved.

PMID- 19754783
TI  - Evaluation of the gene for inducible nitric oxide synthase as a radiosensitizer
      under hypoxic and oxic conditions.
AB  - The radiosensitizing effect of inducible nitric oxide synthase (iNOS) was
      evaluated, in vitro, in a feline vaccine-associated sarcoma (VAS) cell line and a
      canine osteosarcoma cell line (D17). The gene encoding the human iNOS was cloned
      into an expression plasmid under the control of a cytomegalovirus immediate early
      promoter. Transient transfections were performed in feline VAS cells and D17
      cells. Nitric oxide was measured in the supernatant media 48 h later as an
      indirect measurement of iNOS expression. Cells were irradiated using cobalt-60
      under hypoxic or oxic conditions, and clonogenic assays were used to evaluate the
      effects of gene transfer on the sensitivity of cells to radiation. The results
      demonstrated that iNOS had no significant effect on improving the
      radiosensitivity of cells under oxic conditions. However, under hypoxic
      conditions, iNOS gene transfer significantly improved radiosensitization in
      osteosarcoma cells. These results demonstrate the feasibility of improving the
      outcome of radiotherapy in dogs with large bulky tumours using iNOS gene therapy.

PMID- 19754785
TI  - Veterinary cancer registries in companion animal cancer: a review.
AB  - Current and prior veterinary cancer registries are few in number and scattered.
      Different inclusion criteria, dissimilar collection methods and variable
      reference population estimation methods pose obstacles in the comparisons between
      veterinary and human cancer registries. Veterinary cancer registries have yielded
      information on the risk and incidence of different cancer types in certain breeds
      and geographical regions, as well as provided information on genetic and
      environmental risk factors in some cancers. The objective of this article is to
      review the prior and current veterinary cancer registries, the information they
      have contributed and to discuss different issues relating to their structure
      including inclusion criteria, study populations, reference populations utilized
      in evaluations, recorded variables and the outcome from these.

PMID- 19754786
TI  - Quantification of plasma DNA as a prognostic indicator in canine lymphoid
      neoplasia.
AB  - Dogs have a similar incidence of spontaneous cancers as people, and a noninvasive
      test to monitor disease status in dogs would be of great value. Humans with
      cancer often have increased levels of cell-free circulating DNA in their plasma,
      which has shown promise for diagnosis, prognosis and detection of residual
      disease. We hypothesized that dogs with cancer have increased circulating DNA
      compared with healthy dogs or dogs with non-neoplastic diseases. Plasma DNA was
      measured in 40 healthy dogs, 20 dogs with non-neoplastic diseases and 80 dogs
      with cancer. The reference interval for plasma DNA in healthy dogs was 1-15 ng
      mL(-1). Dogs with lymphoma and lymphoid leukaemia had significantly higher
      concentrations (range: 0-91 ng mL(-1), P < 0.0001). Antigen receptor
      rearrangement assays suggest that plasma DNA had the same clonality as the
      primary lymphoid tumours. Dogs with lymphoid neoplasia and plasma DNA >25 ng mL(
      1) had shorter remission times than those with < 25 ng mL(-1) (P = 0.0116). In
      contrast to humans, where increased plasma DNA is seen in many diseases, dogs
      with nonlymphoid malignancies and non-neoplastic diseases had plasma DNA
      concentrations similar to healthy dogs. This study shows that a portion of dogs
      with lymphoid neoplasia have increased tumour-derived plasma DNA, which serves as
      a negative prognostic indicator.

PMID- 19754787
TI  - Treatment of canine mast cell tumours with vinblastine, cyclophosphamide and
      prednisone: 35 cases (1997-2004).
AB  - The purpose of this retrospective study was to determine the efficacy and
      toxicity of a combined protocol of vinblastine, cyclophosphamide and prednisone
      (VCP) in 35 dogs with mast cell tumours (MCTs). Eleven dogs had measurable
      disease (group 1) and 24 dogs had incompletely excised MCT or were at high risk
      for metastasis (group 2). Five patients in group 1 achieved complete response,
      two partial responses, two stable diseases and two progressive diseases. The
      median progression-free survival time (PFST) for group 1 and 2 dogs was 74 and
      865 days, respectively. The median overall survival time (OST) for group 1 and 2
      dogs was 145 and >2092 days, respectively. Significant negative multivariate
      prognostic factors included macroscopic disease and reduced vinblastine (VBL)
      treatments for PFST, and presence of MCT in bone marrow analysis, Patnaik grade
      III MCT and reduced VBL treatments for OST. Toxicity was infrequent and self
      limiting. This study suggests that the VCP protocol should be considered as an
      option in the treatment of MCT in dogs.

PMID- 19754788
TI  - Vinblastine and prednisolone chemotherapy for surgically excised grade III canine
      cutaneous mast cell tumours.
AB  - The effect of treatment with vinblastine and prednisolone chemotherapy in dogs
      undergoing only surgical excision of Patnaik grade III cutaneous mast cell
      tumours is reported. Potential explanatory variables were explored using Kaplan
      Meier survival analysis with log-rank tests. During a median follow-up period of
      429 days, the overall median survival time (MST) was not reached (lower 95% CI =
      322 days). The 1-year survival probability was 0.71 (standard error 0.1),
      remaining unchanged at 2 years. Secondary disease at presentation was an
      independent risk factor for survival (P = 0.045). The MST of dogs presenting with
      secondary disease was 322 days, with a lower 95% confidence interval of 142 days
      and a 1-year survival of probability of 0.47 (standard error 0.19). Adverse
      effects were recorded in 6 of the 108 (5.6%) vinblastine doses given. This
      chemotherapy regimen is a well-tolerated adjunct to surgery for grade III mast
      cell tumours and appears to prolong survival compared with that expected with
      surgery alone.

PMID- 19754789
TI  - A novel small molecule Met inhibitor, PF2362376, exhibits biological activity
      against osteosarcoma.
AB  - The receptor tyrosine kinase Met is dysregulated in several human cancers
      including osteosarcoma (OSA) in which overexpression is a negative prognostic
      indicator and enforced Met expression in normal osteoblasts leads to genomic
      instability and malignant transformation. Met is also known to be inappropriately
      expressed in canine OSA tumour samples and cell lines. The purpose of this study
      was to evaluate the potential utility of an orally bioavailable small molecule
      Met inhibitor, PF2362376, against canine OSA cell lines as a prelude to future
      clinical work. PF2362376 inhibited phosphorylation of Met, Gab-1, Erk and Akt,
      but not of Src or STAT3. Furthermore, PF2362376 inhibited proliferation of canine
      OSA cell lines and induced cell death at biologically achievable concentrations.
      Last, activities associated with Met signalling including migration, invasion,
      branching morphogenesis and colony formation in soft agar were blocked by
      PF2362376. These studies support the notion that Met is a relevant target for
      therapeutic intervention in OSA.

PMID- 19754790
TI  - Chemotherapy during pregnancy: a review of the literature.
AB  - Although diagnosing cancer during pregnancy is uncommon in veterinary medicine,
      when it occurs, chemotherapy may represent a reasonable treatment option. A major
      consideration is that physiological changes associated with pregnancy affect drug
      pharmacokinetics and complicate correct dosing of chemotherapy agents.
      Additionally, most antineoplastic drugs are able to cross the placenta thus
      adversely affecting the foetus. However, favourable outcomes have been observed
      in human beings when chemotherapy has been administered after organogenesis.
      Conversely, chemotherapy should be avoided during the early embryonic and
      organogenesis periods as it might lead to foetal death and/or major
      malformations.

PMID- 19754791
TI  - Is cancer a stem cell disease? Theory, evidence and implications.

PMID- 19754792
TI  - Characterization of the biological behaviour of appendicular osteosarcoma in
      Rottweilers and a comparison with other breeds: a review of 258 dogs.
AB  - The purpose of this retrospective study was to compare Rottweilers diagnosed with
      osteosarcoma (OSA) with other breeds to determine whether Rottweilers experienced
      a more aggressive form of the disease. Two hundred and fifty-eight dogs were
      evaluated (102 clinical and 156 necropsy cases). In the necropsy population,
      Rottweilers had a younger mean age at death (7.3 versus 9 years, P = 0.006).
      There were no significant differences between Rottweilers and other breeds in age
      at diagnosis, median disease-free interval or survival time. However, Rottweilers
      were more likely to have metastasis to the brain (7 versus 0%, P = 0.03). These
      results suggest that OSA in Rottweilers may have a different biological
      behaviour, but this study did not confirm that these differences were associated
      with a worse outcome.

PMID- 19754793
TI  - Inhibition of telomerase in canine cancer cells following telomestatin treatment.
AB  - Telomere shortening in normal somatic cells has been proposed as a major barrier
      to unlimited cellular proliferation. Telomerase is an enzyme capable of
      maintaining telomere length, and thus bypassing this barrier. In human beings,
      telomerase activity is restricted to cancer cells and cells of stem or germ cell
      lineages. Dogs represent a potentially useful clinical model for the development
      of telomerase-based therapies because telomerase activity is also restricted to
      cancer cells and stem cells in this species. We examined the ability of
      telomestatin to inhibit telomerase activity in telomerase-positive D17 and CMT7
      canine cancer cell lines. At a concentration of 2 microM, telomestatin treatment
      resulted in a decrease in telomerase activity, telomere shortening, growth
      inhibition and apoptosis in telomerase-positive cancer cells. These effects were
      not seen in telomerase-negative skin fibroblasts or negative controls. These
      results confirm that telomestatin specifically inhibits telomerase activity in
      canine cancer cells and strengthens the usefulness of dogs as a model for testing
      telomerase-based therapies.

PMID- 19754794
TI  - Immunohistochemical evaluation of p53 expression with different antibodies in
      malignant canine tumours with or without p53 gene mutation.
AB  - Six monoclonal antibodies and a polyclonal antibody (CM1) were used to
      investigate the overexpression of p53 protein by immunohistochemistry (IHC) in
      six sarcomas and 21 mammary carcinomas from 27 dogs. IHC was compared with p53
      gene mutation analysis performed on the same samples. Only the monoclonal PAb240,
      PAb421 and the CM1 antibodies were able to detect expression of canine p53
      protein. CM1 was found to give the highest concordance (8/11) between positive
      expression of the p53 protein by IHC and the presence of a gene mutation. In the
      samples that were negative for p53 expression by IHC, but contained a p53 gene
      mutation according to DNA analysis, the mutation often affected the epitopes that
      could have been recognized by these antibodies. Only one out of 16 tumours
      without a p53 gene mutation had a weakly positive IHC result. These findings
      indicate that in these two types of canine tumours, IHC - particularly with CM1 -
      can detect many alterations in p53 expression owing to a gene mutation. False
      positive results were very infrequent.

PMID- 19754795
TI  - Protein expression profiling of normal and neoplastic canine prostate and bladder
      tissue.
AB  - Prostatic carcinoma is an important cancer in both men and dogs. Dogs have been a
      valuable animal model for investigating prostate cancer, but their relevance is
      unclear as the origin of canine prostatic carcinomas is unknown. We hypothesized
      that a proteomic approach for diagnosis of these neoplasms might provide
      quantitative data useful for more complete characterization of their origin.
      Protein expression profiles were prepared from normal canine prostate glands and
      bladders. The normal protein profiles were then compared with protein expression
      profiles of three canine prostatic carcinomas. Two-dimensional differential in
      gel electrophoresis (2-D DIGE) was used to analyse an average of approximately
      1000 proteins per carcinoma. When compared with normal prostate tissue, the
      carcinomas exhibited greater than 2.5-fold difference in expression for an
      average of 230 proteins. Similar proteomic comparisons between the carcinomas and
      the normal bladder revealed a greater than 2.5-fold difference in expression for
      an average of 208 proteins. Mass spectrometry and protein database homology were
      used to identify nine proteins (alpha-enolase, vimentin, GRP78, endoplasmin
      (GRP94), albumin, keratins 7 and 8, haptoglobin, and transferrin) overexpressed
      by the carcinomas. Statistical testing demonstrated that keratin 7, GRP78, and
      endoplasmin were significantly overexpressed in the carcinomas compared with
      normal prostate or bladder. Principal components analysis revealed that the
      carcinomas formed a unique cluster distinct from either the normal prostate or
      normal bladder. In conclusion, proteomic analysis revealed that whereas the
      majority of proteins expressed by canine prostatic carcinomas are also expressed
      by normal and neoplastic bladder and prostate tissue, the carcinomas contained
      unique protein components that allowed their segregation as a distinct group
      separate from normal canine prostate and bladder. Additionally, several proteins
      uniquely expressed by canine prostatic carcinomas were also identified.

PMID- 19754796
TI  - Erratum.

PMID- 19754797
TI  - Cancer, cyclo-oxygenase and nonsteroidal anti-inflammatory drugs - can we combine
      all three?
AB  - Understanding the molecular biology of cancer and identification of the aberrant
      mechanisms that permit unrestricted cell growth is fundamental to the development
      of cancer treatment and prevention strategies. When defective molecular pathways
      have been uncovered, targeted therapies aimed at specific disruption to the
      biology of the cell can be developed. Such targeted treatments might more
      effectively kill cancer and spare normal tissues. The significance of the cyclo
      oxygenase (COX) enzymatic pathways has emerged over the last 20 years and is
      currently a focus of study in some cancers of humans and veterinary species. This
      pathway is relatively easy to inhibit using nonsteroidal anti-inflammatory drugs
      that are commonly in use in veterinary practice, making this pathway appear as a
      logical target. However, COX is just one of many aberrant cell signalling
      pathways identified in carcinogenesis. This review explores possible benefits and
      current limitations of treating cancer with COX-inhibiting drugs in veterinary
      practice.

PMID- 19754799
TI  - Clinicopathological findings and results of bone marrow aspiration in dogs with
      cutaneous mast cell tumours: 157 cases (1999-2002).
AB  - Bone marrow aspiration for routine staging of canine cutaneous mast cell tumour
      is not consistently performed, and the overall incidence of bone marrow
      infiltration and predictive value of the complete blood count (CBC) is unknown.
      This study evaluated a series of 157 dogs presented for cutaneous mast cell
      tumours in which a CBC and bone marrow aspiration were performed. The incidence
      of bone marrow infiltration at initial staging was low at 2.8%, and 4.5% overall.
      Factors significantly associated with bone marrow infiltration included increased
      age, leucocytosis, anaemia, neutrophilia, monocytosis, eosinophilia,
      thrombocytopenia, being purebred and staging at the time of recurrent or
      progressive disease. Our study suggests that a bone marrow sample is not
      indicated for routine staging but maybe indicated for those dogs with mast cell
      tumours having either an abnormal haemogram (neutrophilia, monocytosis,
      eosinophilia, basophilia, anaemia and thrombocytopenia) or presenting for tumour
      regrowth, progression or new occurrence.

PMID- 19754800
TI  - Efficacy of injectable maropitant (Cerenia) in a randomized clinical trial for
      prevention and treatment of cisplatin-induced emesis in dogs presented as
      veterinary patients.
AB  - Chemotherapy-induced nausea and vomiting (CINV) is a common side-effect of
      cisplatin therapy. Maropitant (Cerenia), a novel neurokinin-1 receptor
      antagonist, was evaluated for prevention and treatment of cisplatin-induced
      emesis in tumour-bearing dogs. Dogs (n = 122) were randomly allocated to three
      treatment groups: T01, placebo before and after cisplatin; T02, placebo before
      and maropitant after cisplatin; or T03, maropitant before and placebo after
      cisplatin. Maropitant treatment (T02) following a cisplatin-induced-emetic event
      resulted in significantly fewer subsequent emetic events (P = 0.0005) than in
      placebo-treated dogs (T01). In placebo-treated (T01) dogs, 56.4% were withdrawn
      from the study because of treatment failure compared with 5.3% in group T02. When
      maropitant was administered prior to cisplatin treatment (T03) in a prevention
      regime, 94.9% did not vomit compared with only 4.9% of placebo-treated dogs, and
      significantly fewer emetic events (P < 0.0001) were observed in those dogs that
      did vomit. In summary, maropitant was safe and highly effective in reducing or
      completely preventing cisplatin-induced emesis.

PMID- 19754798
TI  - Five decades of progress in haematopoietic cell transplantation based on the
      preclinical canine model.
AB  - The preclinical canine model has proved valuable for the development of
      principles and techniques of haematopoietic cell transplantation (HCT) applicable
      to human patients. Studies in random-bred dogs concerning the impact of
      histocompatibility barriers on engraftment and graft-versus-host disease, the
      kinetics of immunological reconstitution, the efficacy of various pretransplant
      conditioning regimens, post-transplantation immunosuppression protocols,
      treatment of malignant diseases, and graft-versus-tumour effects have advanced
      HCT from an investigational therapy with uncertain clinical benefit half a
      century ago to an important treatment choice for thousands of patients treated
      annually in transplantation centres worldwide. More recent preclinical canine
      studies have resulted in the clinical translation of non-myeloablative, minimally
      invasive transplantation protocols that have extended allogeneic HCT to include
      older human patients with malignant and non-malignant, acquired or inherited
      haematological disorders, and those with comorbid conditions. Here, we review the
      contributions of the canine model to modern HCT and describe the usefulness of
      HCT for the treatment of canine haematological disorders.

PMID- 19754801
TI  - 3-Phosphoinositide-dependent protein kinase-1/Akt signalling and inhibition in a
      canine prostate carcinoma cell line.
AB  - Deregulation of the 3-phosphoinositide-dependent protein kinase-1 (PDK-1)/Akt
      signalling pathway is associated with prostate cancer development and
      progression. Inhibition of PDK-1/Akt signalling can be achieved using
      structurally optimized celecoxib derivatives such as OSU-03012. In this study, we
      treated the novel canine prostate cancer cell line, Ace-1, with OSU-03012 or
      dimethyl sulphoxide in vitro. We found that Akt was constitutively phosphorylated
      in the canine prostate cancer cell line Ace-1 and that there was a dose-dependent
      decrease in cell viability, and Akt and glycogen synthase kinase-3beta
      phosphorylation, in response to OSU-03012 treatment. This was accompanied by a
      dose-dependent increase in apoptosis. These data suggest that Akt signalling
      pathway inhibition is a potential strategy for the treatment of dogs with
      prostate cancer and that canine prostate cancer is a relevant large animal model
      for evaluating Akt pathway inhibitors such as OSU-03012 for use in people.

PMID- 19754803
TI  - Interactions between radiation therapy and immunotherapy: the best of two worlds?
AB  - Contrary to earlier thought, there is now accumulating evidence that local
      radiation therapy and various form of immunotherapy may be complementary. This
      may occur as a result of radiation-induced changes to the tumour cells
      themselves, the tumour microenvironment, the tumour vasculature and modulation of
      antigen-presenting and effector cell function. This study discusses recent
      findings and potential applications of this apparent synergy.

PMID- 19754804
TI  - Microvascular growth of 7,12-dimethylbenz(alpha)anthracene-induced
      adenocarcinomas in rats: histology and scanning electron microscopy of resin
      casts.
AB  - Vascular changes at various stages of growth of 7,12
      dimethylbenz(alpha)anthracene (DMBA)-induced mammary adenocarcinomas in 22 female
      Sprague-Dawley rats were investigated using histology, immunohistochemistry and
      scanning electron microscopy (SEM) of corrosion casts. In the early stage of
      tumour growth, capillaries within the neoplasms were thin, with 8-10 microm
      diameter, and characterized by rows of vascular sprouts representing extensive
      neovascularization and formation of a high-density capillary plexus. In the
      intermediate stage of tumour growth, the growing tumour was multi-nodular and
      tumour cells were arranged in a tubulopapillary pattern. Capillaries formed
      spheroid vascular capsules and were characterized by dilation, to a diameter of
      10-80 mum, and blind ends. In the late stage of tumour growth, a remarkable
      reduction in the number of vascular endothelial growth factor-positive cells and
      Ki-67-stained nuclei was demonstrated. The tunica media of nutritive arteries
      displayed a tendency to atrophy. Many arteriovenous anastomoses between the major
      arteries and the veins were found in regions just before their entry into the
      tumour. The central regions of the tumour were degenerative and necrotic, and
      vasculature was confined to surface regions of the tumour, forming a basket-like
      configuration around the avascular central regions. Resin leakages representing
      haemorrhage or oedema and distortions such as flattening, break-off and
      strangulations of capillaries were frequently observed, all of which are known as
      late tumour signs. We concluded that these microvascular alterations might change
      the homogeneity of tumour perfusion and contribute to necrosis in central
      portions of the tumour.

PMID- 19754805
TI  - Coarse fractionated radiation therapy for pituitary tumours in cats: a
      retrospective study of 12 cases.
AB  - This retrospective study describes the clinical progression of 12 cats with
      pituitary tumours treated with a coarse fractionated radiation protocol
      delivering a total dose of 37 Gy in five once weekly fractions. A pituitary
      macrotumour was identified in all 12 cats: 4 with neurological signs only and 8
      with insulin-resistant diabetes mellitus secondary to acromegaly. One of the cats
      with central neurological signs died before completing the radiotherapy course;
      the remaining three had partial or complete remissions of their central
      neurological signs. Of the cats with unstable diabetes mellitus, five no longer
      required insulin therapy, one required less insulin and two became stable. The
      overall median survival time was 72.6 weeks; four cats died from related causes,
      two from unrelated problems and six remain alive. Radiation therapy is confirmed
      as an effective treatment for feline pituitary tumours, giving prolonged survival
      and control of both paraneoplastic and mass effect signs.

PMID- 19754806
TI  - High-dose-rate brachytherapy for intranasal tumours in dogs: results of a pilot
      study.
AB  - This prospective study describes the feasibility and toxicity of (192)Iridium
      high-dose-rate (HDR) brachytherapy as an alternative strategy for the treatment
      of canine intranasal tumours. Fifteen dogs with malignant intranasal tumours were
      treated twice weekly using a hypofractionated protocol with eight fractions, 5 Gy
      per fraction, resulting in a total dose of 40 Gy. Acute and chronic adverse side
      effects appeared to be rare. Only 7% of the acute side-effects and 5% of the
      chronic were classified as severe (grade 3). Eight dogs showed clinical complete
      remission, and five dogs had partial remission, with a resolution of tumour
      related symptoms. Magnetic resonance imaging showed a reduced tumour mass in 12
      cases. Median survival time was 17 months (range 4-48 months), with four dogs
      (three without disease) still alive. Median time to recurrence of these dogs was
      14 months. In nine dogs, progression or recurrence of the tumour was the cause of
      death. This study suggests that HDR brachytherapy is feasible and well tolerated.

PMID- 19754807
TI  - Development of a new canine osteosarcoma cell line.
AB  - Establishing a canine osteosarcoma (OSA) cell line can be useful to develop in
      vivo and in vitro models of OSA. The goal of this study was to develop,
      characterize and authenticate a new canine OSA cell line and a clone. A cell line
      and a clone were developed with standard cell culture techniques from a naturally
      occurring OSA in a dog. The clonal cell line induced a tumour after injection in
      RAG 1-deficient mouse. Histology was consistent with OSA. The original tumour
      from the dog and the tumour induced in the mouse were both reactive with vimentin
      and osteonectin (ON). The parent cell line and clonal cell line were reactive
      with ON, osteocalcin and alkaline phosphatase. Loss of heterozygosity was found
      in the same three microsatellite markers in the parent and clonal cell lines, and
      the tumour tissue grown in the mouse.

PMID- 19754809
TI  - Breed, gender and neutering status of British dogs with anal sac gland carcinoma.
AB  - This study details the breed, gender and neutering status of a large cohort of
      British canine patients suffering from histologically confirmed anal sac gland
      carcinoma. Estimates of the relative risk for the development of this disease
      attributable to these factors are calculated. To reduce the impact of sampling
      errors, cases were selected from veterinary histopathology laboratories rather
      than referral hospital databases, and multiple estimates of the general British
      canine population were used. The weaknesses of the statistical assumptions made
      are discussed. There was no evidence to support a gender predisposition for the
      development of this condition. English cocker spaniels are significantly over
      represented, with a mean relative risk estimate of 7.3. The mean relative risk
      estimate associated with being neutered was 1.4; the effect of neutering appeared
      to be more significant in male dogs compared with that in female dogs.

PMID- 19754810
TI  - Expression of receptor tyrosine kinases VEGFR-1 (FLT-1), VEGFR-2 (KDR), EGFR-1,
      PDGFRalpha and c-Met in canine primary brain tumours.
AB  - Inhibition of tumour growth and angiogenesis by targeting key growth factor
      receptors is a promising therapeutic strategy for central nervous system tumours.
      Characterization of these growth factor receptors in canine primary brain tumours
      has not been done. Using quantitative real-time TaqMan polymerase chain reaction
      (PCR), we evaluated the expression of messenger RNA (mRNA) for five tyrosine
      kinase growth factor receptors (vascular endothelial growth factor receptor
      [VEGFR]-1, VEGFR-2, endothelial growth factor receptor [EGFR]-1, platelet-derived
      growth factor receptor a [PDGFRa], and c-Met) relative to normal cerebral cortex
      in 66 spontaneous canine primary brain tumours. Increased expression of VEGFR-1
      and VEGFR-2 mRNA was greatest in grade IV astrocytomas (glioblastoma multiforme)
      and grade III (anaplastic) oligodendrogliomas. EGFR-1 mRNA expression was more
      consistently increased than the other receptors in all tumour types, while
      increased PDGFRa mRNA expression was mostly restricted to oligodendrogliomas. The
      similarities in increased expression of these tyrosine kinase growth factor
      receptors in these canine tumours, as compared to data from their human
      counterparts, suggest that common molecular mechanisms may be present.

PMID- 19754811
TI  - Telomerase activity and telomerase reverse transcriptase catalytic subunit
      expression in canine lymphoma: correlation with Ki67 immunoreactivity.
AB  - Increased telomerase activity (TA) has been found in human and canine solid
      tumours, stem cells and somatic tissues with enhanced proliferative potential.
      The relationship between TA in normal and malignant lymphoid tissues remains
      unclear. The TA and the expression of canine telomerase reverse transcriptase
      catalytic subunit (dogTERT) messenger RNA (mRNA) were analyzed in malignant lymph
      nodes from 30 dogs with lymphoma, from two dogs with non-neoplastic illness and
      from two clinically normal dogs, demonstrating a statistically significant
      difference between TA in lymphoma lymph nodes (n = 30) and normal nodes (n = 4)
      but no significant difference in dogTERT mRNA expression. In addition, the
      expression of telomerase reverse transcriptase catalytic subunit (TERT) protein
      and Ki67 was analyzed in malignant lymph nodes from 10 dogs with lymphoma and
      from two clinically normal dogs by immunohistochemistry. TERT expression was
      associated with Ki67 in all lymphoma nodes (n = 10), and differences were
      illustrated between TERT and Ki67 expression between lymphoma (n = 10) and non
      lymphoma (n = 2) nodes. This data support further investigation of telomerase in
      canine haematopoietic neoplasia through large-scale prospective studies.

PMID- 19754812
TI  - Mohs micrographic surgery: a technique for total margin assessment in veterinary
      cutaneous oncologic surgery.
AB  - Mohs micrographic surgery (MMS) is the gold standard for the excision of locally
      invasive cutaneous malignancies in human dermatological surgery. Using a unique
      horizontal sectioning technique, MMS enables 100% surgical margin assessment and
      provides the lowest recurrence rates for locally invasive tumours. The purposes
      of this preliminary study were to explore the feasibility of application of MMS
      in the veterinary setting and to establish practical advantages and limitations
      of its use in a pilot programme. It was hypothesized that MMS technique could
      provide 100% tumour margin assessment using frozen and/or formalin-fixed
      horizontal histopathologic sections. Tumour excision and colour-coded mapping
      were performed, and specimen tissue was fixed using either frozen sections or
      formalin-fixed sections. Horizontal sections were assessed for quality and
      presence and location of neoplastic cells based on the mapped orientation. The
      MMS technique was used in the excision of six squamous cell carcinomas and five
      mast cell tumours. In all cases, the MMS permitted 100% tumour margins
      examination.

PMID- 19754813
TI  - Expression and sequence of canine SIRT2 and p53 genes in canine mammary tumour
      cells - effects on downstream targets Wip1 and p21/Cip1.
AB  - We have characterized gene dysfunction in a cellular model of spontaneous canine
      mammary cancer by investigating specific gene defects in SIRT2 and p53 genes for
      comparative studies among canine tumour-derived cell lines. These genes and their
      downstream targets are involved in regulating gene silencing, cell cycle
      progression and prevention of senescence and apoptosis. Canine SIR2 reverse
      transcriptase-polymerase chain reaction amplicons were most homologous to human
      SIRT2 and revealed detectable transcripts in all cell lines. Canine SIRT2
      contained non-conserved amino acid substitutions, representing mutations or
      allelic differences and interspecies differences. Sequence differences between
      individuals in p53 and SIRT2 were found in two cell lines including a stop codon
      in p53 and substitutions of conserved cysteine residues in the Zn(2+)-binding
      motif in SIRT2. Mutations in SIRT2 were coincident with expression of the p53
      modulator, Wip1; a failure to activate p21/Cip1 and extended G2/M phase. A third
      cell line appeared to function normally in these two pathways and likely
      possesses other defects in proliferation-control genes. This data identify
      potentially important defects in pathways regulated by p53 and SIRT2 that
      modulate cell proliferation and integrate development, apoptosis and
      proliferative lifespan. These genes offer promising therapeutic targets,
      contributing to the transformed/immortalized phenotype in spontaneous canine
      mammary cancer.

PMID- 19754814
TI  - Cytological comparison of fine-needle aspirates of liver and spleen of normal
      dogs and of dogs with cutaneous mast cell tumours and an ultrasonographically
      normal appearing liver and spleen.
AB  - Staging of dogs with cutaneous mast cell tumours (MCTs) is an important
      diagnostic step. Aspiration of the liver and the spleen is often part of routine
      staging. This study cytologically compared mast cell numbers in fine-needle
      aspirates of liver and spleen of clinically normal unaffected dogs with those of
      dogs with cutaneous MCT and an ultrasonographically normal appearing liver and
      spleen. The unaffected dogs (n = 32) were selected from humane society dogs, and
      the affected dogs (n = 51) were selected from hospital cases. There were no
      statistically significant differences in each of the parameters evaluated for the
      liver aspirates. For splenic aspirates, affected dogs showed significantly more
      mast cells per cluster (P = 0.04) and more isolated mast cells per slide (P =
      0.03) compared with unaffected dogs. However, no clinically important difference
      existed between the unaffected and affected dogs; thus, routine aspiration of an
      ultrasonographically normal appearing liver and spleen of dogs with cutaneous MCT
      does not appear to be a clinically useful staging tool.

PMID- 19754815
TI  - Telomerase activity in canine osteosarcoma.
AB  - Appendicular osteosarcoma (OSA) is the most common primary bone tumour in dogs,
      and the prognosis with standard of care therapy of amputation and adjunctive
      chemotherapy is generally poor, with median survival times of 1 year. The ability
      of neoplastic cells to maintain their telomere length, by either telomerase
      activity or alternate methods, is an important step in tumour development and
      malignancy. The purpose of this study was to determine the presence of telomerase
      activity in canine OSA. To evaluate the frequency of alternative lengthening of
      telomeres in canine OSA, we have used the telomeric repeat amplification protocol
      in five canine cell lines and in six samples taken from clinical patients at the
      time of amputation. Our results reveal the presence of telomerase activity in
      100% of canine OSA cell lines and 83% of clinical samples evaluated. This is in
      contrast to human OSA where 25-40% expression levels of telomerase are reported.
      Importantly, our results not only suggest that canine OSA may serve as a good
      model for aggressive telomerase-positive forms of human OSA but also that
      antitelomerase therapy strategies for treatment of canine OSA may be more
      successful than in the treatment of majority of human patients with OSA.

PMID- 19754816
TI  - Histiocytic sarcomas in flat-coated retrievers: a summary of 37 cases (November
      1998-March 2005).
AB  - Thirty-seven cases of histiocytic-like sarcomas (HLSs) in flat-coated retriever
      dogs were evaluated retrospectively. This tumour accounted for 36% of the
      malignant tumours seen in this breed during the study period. The median age at
      presentation was 8.2 years. Thirty-four dogs presented with a swelling or mass in
      a muscle group or surrounding a joint. The remaining three presented for rib (1),
      cutaneous (1) or primary splenic origin (1). A high rate of metastasis to local
      lymph nodes (45%), thorax (20%) and abdominal organs (20% confirmed) was seen.
      Overall metastastic rate by the time of death was 70%. The median survival for
      all dogs was 123 days. The most significant prognostic indicator was presence of
      distant metastasis at the time of diagnosis with median survival of 68 or 200
      days, with or without metastasis, respectively. Chemotherapy and radiation
      therapy significantly improved survival. Dogs given chemotherapy survived a
      median of 185 versus 34 days for dogs that were not (P = 0.0008). Dogs treated
      with radiation survived a median of 182 versus 60 days for those that were not (P
      = 0.0282). Dogs receiving only palliative therapy survived a median of 17 versus
      167 days in dogs receiving any kind of radiation, chemotherapy, surgery or
      combinations. A set protocol of radiation and CCNU (RTCCNU) induced minimal
      toxicity and provided a median survival of 208 versus 68 days for all other dogs.
      While this tumour carries a poor long-term prognosis in flat-coated retrievers,
      it is reasonable to treat these dogs for palliation of signs and extension of
      life.

PMID- 19754817
TI  - A feasibility study of low-dose total body irradiation for relapsed canine
      lymphoma.
AB  - Seven client owned dogs with confirmed relapsed lymphoma were enrolled in a
      prospective feasibility study investigating the effects of low-dose total body
      irradiation (LDTBI) delivered in a single 1 Gy fraction. LDTBI for relapsed
      lymphoma was safe and well tolerated. The only major side-effect of LDTBI was
      asymptomatic thrombocytopenia in all dogs. The median platelet nadir was
      17,000/microL (range 4000-89,000), which occurred a median of 10 days (range 8
      30) post irradiation. Three dogs had short-term partial responses, two stable
      disease and two progressive disease (PD). Six dogs were euthanatized for PD, and
      one dog died while in partial remission. No dogs had clinical complications.
      Survival analysis was not performed, because the study design did not allow for
      evaluation of survival time. Larger studies incorporating LDTBI in the
      induction/consolidation phase of treatment need to be performed to determine the
      therapeutic efficacy of LDTBI.

PMID- 19754818
TI  - Feline head and neck squamous cell carcinoma: a natural model for the human
      disease and development of a mouse model.
AB  - Head and neck squamous cell carcinoma (H/N SCC) is a devastating disease in
      humans and cats, and shares similar features between the two species. The large
      population of pet cats in the United States, along with the high incidence of
      oral SCC in the cat, makes the cat an attractive candidate as a natural model for
      the human disease. There are similarities in pathology, progression, outcome,
      resistance to treatment, possible aetiologies and p53 expression, and we discuss
      the benefits of the cat as a natural model. We describe the development of a nude
      mouse xenograft model of feline oral SCC using the SCCF1 cell line transfected
      with a luciferase expression construct. In vivo tumour growth and metastasis were
      measured using serial bioluminescent imaging, and tumours grew best in the
      subcutis. The cat and nude mouse models will be useful to investigate the
      pathogenesis and the molecular basis of H/N SCC, and for preclinical drug
      screening.

PMID- 19754819
TI  - Palliative radiotherapy as treatment for non-resectable soft tissue sarcomas in
      the dog - a report of 15 cases.
AB  - Fifteen dogs with various non-resectable soft tissue sarcomas were treated with a
      palliative protocol of Cobalt(60) radiation. Twelve (80%) of the 15 tumours were
      fibrosarcomas and haemangiopericytomas. Total tumour radiation dose was 24 Gy,
      given in three 8 Gy fractions, on days 0, 7, 21 or weekly. Thirteen tumours (87%)
      responded with stable disease; median time to progression and median survival
      time were 263 and 332 days, respectively. Radiation toxicity was negligible. The
      survival and local control with this palliative protocol are almost comparable
      with curative intent primary radiotherapy.

PMID- 19754820
TI  - Establishment of four pairs of canine mammary tumour cell lines derived from
      primary and metastatic origin and their E-cadherin expression.
AB  - Four new pairs of canine mammary carcinoma cell lines derived from both primary
      and metastatic lesions were established. The cells were cultured in RPMI-1640
      with 10% fetal bovine serum and they showed stable growth for more than 120
      passages. Using these cell lines, the expression of E-cadherin was measured by
      flow cytometry and the function of E-cadherin was evaluated by cell aggregation
      assay and results from the primary and metastatic lesions were compared
      statistically. E-cadherin was strongly expressed in all of the cell lines,
      without a notable difference between cells of primary and metastatic origin. In
      the cell aggregation assay, the function of E-cadherin was significantly weaker
      in the cells of primary origin (p < 0.05), as compared with cells of metastatic
      origin. The present results suggest that a reduction in E-cadherin function may
      be implicated in the invasive and metastatic potential of canine mammary tumour
      cells; however, further study will be needed to clarify E-cadherin function in
      the context of the metastasis of canine mammary carcinoma.

PMID- 19754821
TI  - Clinical usefulness of intradermal fluorescein and patent blue violet dyes for
      sentinel lymph node identification in dogs.
AB  - The first lymph node receiving drainage from a specific anatomic region is
      referred to as the sentinel lymph node (SLN). This study sought to evaluate the
      intradermal use of two dyes, patent blue violet (PBV) and fluorescein (FL), for
      SLN mapping in the dog. Multiple intradermal injections were performed in five
      healthy dogs using two dyes, PBV in 0.9% NaCl and FL in solutions of 0.9% NaCl
      and 6% hetastarch. Skin flaps were raised and followed to the first area of
      discrete stain uptake. Areas of uptake were identified as lymph nodes grossly and
      by cytology. Identification of a SLN for each area of intradermal injection was
      accomplished for 98% of the injection sites. Intradermal injections of both PBV
      and FL dyes produce readily visible staining of lymphatic vessels and SLNs in
      healthy dogs and are sufficient to allow ready identification of these structures
      during postmortem dissection.

PMID- 19754822
TI  - Oncology co-operation in the UK.

PMID- 19754823
TI  - Veterinary and Comparative Oncology: onwards and upwards.

PMID- 19754824
TI  - Evaluation of risk and clinical outcome of mast cell tumours in pug dogs.
AB  - Mast cell tumours (MCT) are common in dogs and characterized by diverse biologic
      behaviour. Our objective was to evaluate the risk of MCT in pugs and to describe
      the clinical behaviour of MCT in this breed. Data obtained from the Veterinary
      Medicine Database demonstrate significantly increased frequency of MCT in pugs
      compared with other dogs (OR = 2.28, 95% CI = 1.81-2.86). The medical records for
      25 purebred pugs with a histologic diagnosis of MCT were reviewed. Multiple
      cutaneous tumours were documented in 14 (56 %) of the dogs. Histologic review of
      64 tumours from these dogs confirmed that most tumours (94%) were low to
      intermediate grade. Sixty-four per cent of these dogs are still living, while
      only three dogs (12%) have died due to mast cell disease. A median survival time
      has not been reached. The median follow-up time is 660 days from the diagnosis of
      the first MCT. We conclude that MCT in pugs are relatively benign, despite the
      presence of multiple cutaneous tumours in most cases. Multiple tumours in breeds
      with predisposition to MCT may indicate separate primaries rather than advanced
      stage disease.

PMID- 19754825
TI  - Toxicity and biodistribution of an iodine-131-radiolabelled tumour necrosis
      targeting antibody in non-tumour-bearing domestic felines.
AB  - The potential of human immunotherapeutics now revolutionizing modern cancer
      therapy has yet to make an impact in veterinary medicine, mainly due to the
      evolutionary differences between human and non-human cell surface antigens which
      bar the efficacy for many antibodies targeting human antigens. Here, we explore
      the possible use of an iodine-131 (I-131)-radiolabelled chimericTNT-1/B antibody,
      Cotara, being tested in humans, which targets a highly conserved structure
      present in all solid tumours. The goal was to document the possible toxic side
      effects, retention, excretion and biodistribution of Cotara in non-tumour-bearing
      felines. The study was conducted with six lab animal domestic shorthaired
      felines. Two felines were randomly placed into three dose groups: 1.5, 2.0, and
      3.0 mCi kg(-1) (0.68, 0.9 and 1.36 mCi lb(-1)); these doses were administered by
      a single IV injection. Thyroid blockade with potassium iodide (KI) was
      administered orally once daily. Over the 90-day study, haematologic test results,
      serum chemistry, thyroid function, food intake and morbidity were recorded. Drug
      distribution was ascertained through nuclear scintigraphy. Four of the six
      subjects had decreased appetite (Grade 1) that started on day 4 and then resolved
      by day 10. Two subjects exhibited intermittent days of anorexia (Grade 2) from
      day 5 to day 13. Both subjects with Grade 2 anorexia were sacrificed and
      necropsied once each exhibited two consecutive days of signs. Vomiting (Grade 2)
      occurred in 3 subjects from day 4 to day 13. Three subjects had moderate
      regenerative anaemia (Grade 2), whereas two developed leucocytosis. Overall, a
      single intravenous dose of Cotara resulted in moderate toxicity, with subjects
      exhibiting transitory signs of anorexia and vomiting without laboratory evidence
      of organ pathology. Each subject received a once daily oral dose of KI (33 mg)
      that was found to be safe and effective in the prevention of radiation damage to
      the thyroid gland over the study period. With a moderate toxicity profile, Cotara
      may hold unique promise by delivering I-131 directly into solid tumours of
      various types in felines.

PMID- 19754826
TI  - Efficacy and toxicity of BOPP and LOPP chemotherapy for the treatment of relapsed
      canine lymphoma.
AB  - Mechlorethamine (Mustargen), Oncovin) (vincristine), procarbazine and prednisone
      (MOPP) chemotherapy is useful for relapsed canine lymphoma. This study evaluates
      the efficacy of MOPP after substitution of CCNU (lomustine, LOPP protocol) or
      BCNU (carmustine, BOPP protocol) for mechlorethamine in 60 dogs with relapsed
      lymphoma. Seven of 14 (50%) dogs treated with BOPP responded, for a median of
      129.5 days for complete responders (range 9-354 days) and a median of 140 days
      for partial responders (range 4-276 days). Twenty-three of 44 (52%) dogs treated
      with LOPP responded for a median of 112 days for complete responders (range 48
      250 days) and a median of 84.5 days for partial responders (range 69-290 days).
      Two dogs receiving a combination of LOPP and BOPP partially responded for 28 and
      163 days, respectively. With BOPP chemotherapy, nine dogs (20.5%) and seven dogs
      (50%) had one or more episodes of Grade II or higher neutropenia and
      thrombocytopenia, respectively. Seven dogs (50%) had one or more episodes of
      Grade II or higher gastrointestinal toxicity. While receiving LOPP chemotherapy,
      28 dogs (63.6%) and 17 dogs (38.6%) had one or more episodes of Grade II or
      higher neutropenia and thrombocytopenia, respectively. Seventeen dogs (38.6%) had
      one or more episodes of Grade II or higher gastrointestinal toxicity. Overall,
      there were 17 non-fatal treatment-related episodes of sepsis requiring
      hospitalization. Eight dogs (13%) died or were euthanized because of treatment
      related sepsis and/or chemotherapy-related complications. Severe haematologic
      toxicity, coupled with the improved response duration observed in dogs receiving
      reduced doses during B/L-OPP rescue, underscores the need for protocol
      optimization.

PMID- 19754827
TI  - Epidermal growth factor receptor expression in feline oral squamous cell
      carcinomas.
AB  - Feline oral squamous cell carcinomas (SCC) have a poor prognosis despite
      aggressive treatment with surgery, radiation and anticancer drugs. Overexpression
      of the epidermal growth factor receptor (EGFR), a membrane-bound tyrosine kinase
      receptor, has been found in many human epithelial neoplasms, including oral SCC.
      EGFR overexpression has been associated with advanced disease and a poor
      prognosis. The purpose of this study was to determine whether feline oral SCC
      express EGFR. Thirteen formalin-fixed paraffin wax-embedded biopsy samples from
      feline oral SCC were analysed for EGFR expression using immunohistochemistry.
      Nine of 13 tumours (69%) were positive for EGFR expression, suggesting that
      altered EGFR expression plays a role in feline oral SCC and provides a rationale
      for a potential clinical benefit using EGFR inhibitors in combination with
      conventional treatments.

PMID- 19754828
TI  - Surgical cytoreduction for the treatment of non-lymphoid vertebral and spinal
      cord neoplasms in cats: retrospective evaluation of 26 cases (1990-2005).
AB  - Medical records of 26 cats with non-lymphoid vertebral and spinal cord neoplasms
      treated surgically were reviewed to determine outcome and prognostic factors for
      survival. Of the factors examined, only tumour phenotype was significantly
      associated with survival. Osteosarcoma (3/26 cats) and meningioma (16/26 cats)
      were the most common malignant and benign tumours, respectively. The median
      survival time for cats with malignant neoplasms was 110.5 days, compared with 518
      days for cats with benign tumours. Cytoreductive surgery resulted in clinical
      improvement in 25/26 cats, but local treatment failure occurred in 10/26 cats.
      Overall, 19/26 cats died of confirmed (12/19) or suspected (7/19) tumour-related
      causes, including all eight cats with malignant neoplasms. Results suggest that
      contemporary neurosurgical techniques commonly result in incomplete excision of
      feline non-lymphoid vertebral and spinal cord tumours but are efficacious at
      palliation of clinical signs of spinal cord dysfunction.

PMID- 19754829
TI  - Carboplatin for treatment of a Sertoli cell tumor in a mallard (Anas
      platyrhynchos).
AB  - A 13-year-old male mallard was diagnosed with a non-resectable Sertoli cell tumor
      involving the left testis. The duck was treated with four doses of single-agent
      carboplatin given at 4- to 5-week intervals. Heteropenia, 2 weeks after each
      treatment, was the acute dose-limiting toxicity. The tumor reduced in size by
      25%, and the duck's clinical condition improved for 12 months. Sertoli cell
      tumors are rare in birds, and this is the first report, to our knowledge, of
      attempted chemotherapy treatment in the veterinary literature.

PMID- 19754830
TI  - Extragenital transmissible venereal tumour associated with circulating neoplastic
      cells in an immunologically compromised dog.
AB  - An adult male intact boxer was presented because of diffuse cutaneous nodules.
      Fine-needle aspirate revealed transmissible venereal tumour (TVT) cells.
      Neoplastic cells were also observed in the peripheral blood. Associated
      simultaneous diseases included leishmaniosis, demodicosis, papillomatosis and
      coccidiosis. Immunosuppression may have aggravated disease and triggered
      widespread metastases. The dog was hospitalized and administered oral
      amoxicillin/clavulanate, subcutaneous meglumine antimonite to treat leishmaniosis
      and oral chlortetracycline to treat coccidiosis. Intravenous injection of
      vincristine at weekly interval was used to treat TVT. A rapid regression of
      cutaneous nodules was noted; however, intractable diarrhoea developed, eventually
      leading to death after 18 days. This is the first report describing an unusual
      case of extragenital TVT associated with circulating neoplastic cells in an
      immunosuppressed dog presenting with multiple cutaneous nodules.

PMID- 19754833
TI  - Guidance for non-gynaecological cytology--a platform for the future.

PMID- 19754834
TI  - BSCC code of practice for non-gynaecological cytology: what are the next steps?

PMID- 19754835
TI  - BSCC Code of Practice--fine needle aspiration cytology.
AB  - The British Society for Clinical Cytology Code of Practice on fine needle
      aspiration cytology complements that on exfoliative cytopathology, which was
      published in the last issue (Cytopathology 2009;20:211-23). Both have been
      prepared with wide consultation within and outside the BSCC and have been
      endorsed by the Royal College of Pathologists. A separate code of practice for
      gynaecological cytopathology is in preparation. Fine needle aspiration (FNA)
      cytology is an accepted first line investigation for mass lesions, which may be
      targeted by palpation or a variety of imaging methods. Although FNA cytology has
      been shown to be a cost-effective, reliable technique its accurate interpretation
      depends on obtaining adequately cellular samples prepared to a high standard. Its
      accuracy and cost-effectiveness can be seriously compromised by inadequate
      samples. Although cytopathologists, radiologists, nurses or clinicians may take
      FNAs, they must be adequately trained, experienced and subject to regular audit.
      The best results are obtained when a pathologist or an experienced and trained
      biomedical scientist (cytotechnologist) provides immediate on-site assessment of
      sample adequacy whether or not the FNA requires image-guidance. This COP provides
      evidence-based recommendations for setting up FNA services, managing the
      patients, taking the samples, preparing the slides, collecting material for
      ancillary tests, providing rapid on-site assessment, classifying the diagnosis
      and providing a final report. Costs, cost-effectiveness and rare complications
      are taken into account as well as the time and resources required for quality
      control, audit and correlation of cytology with histology and outcome.
      Laboratories are expected to have an effective quality management system
      conforming to the requirements of a recognised accreditation scheme such as
      Clinical Pathology Accreditation (UK) Ltd.

PMID- 19754836
TI  - Ectopic expression of MgSM1, a Cerato-platanin family protein from Magnaporthe
      grisea, confers broad-spectrum disease resistance in Arabidopsis.
AB  - Proteins belonging to the newly identified Cerato-platanin (CP) family have been
      shown to have elicitor activity in inducing disease resistance responses in
      various plants. In this study, we characterized a gene, MgSM1, from Magnaporthe
      grisea, encoding a putative small protein belonging to the CP family. MgSM1 was
      constitutively expressed not only in different fungal growth stages but also
      during its infection process in rice plants. Agrobacterium-mediated transient
      expression of MgSM1 in Arabidopsis resulted in hypersensitive response in the
      infiltrated local leaves and enhanced disease resistance against Botrytis cinerea
      and Pseudomonas syringae pv. tomato (Pst) DC3000 in upper leaves of plants,
      accompanyed by up-regulated expression of defense genes (PR-1, PR-5 and PDF1.2).
      Transgenic Arabidopsis plants expressing MgSM1 under control of a dexamethasone
      (DEX)-inducible promoter were generated. Expression of MgSM1 in transgenic plants
      was induced by exogenous application of DEX. MgSM1-expressing plants showed
      normal growth with application of <10 microm DEX. After DEX induction, the MgSM1
      expressing plants showed enhanced disease resistance against B. cinerea,
      Alternaria brassicicola and Psto DC3000 as well as up-regulated expression of
      some of defense genes. Moreover, accumulation of reactive oxygen species was
      observed in MgSM1-expressing plants. These results collectively suggest that
      ectopic expression of MgSM1 in transgenic plants confers broad-spectrum
      resistance against different types of pathogens. Our study also provides a novel
      strategy to generate environment-friendly crops with enhanced broad-spectrum
      resistance through ectopic expression of microbe-derived disease resistance
      inducing proteins.

PMID- 19754837
TI  - Significant reduction of fungal disease symptoms in transgenic lupin (Lupinus
      angustifolius) expressing the anti-apoptotic baculovirus gene p35.
AB  - Narrow-leafed lupin (NLL; Lupinus angustifolius) is a recently domesticated but
      anciently propagated crop with significant value in rotation with cereals in
      Mediterranean climates. However, several fungal pathogens, traditionally termed
      necrotrophs, severely affect broad-acre production and there is limited genetic
      resistance in the NLL germplasm pool. Symptoms of many of these diseases appear
      as localized areas of dead cells exhibiting markers of programmed cell death.
      Based on our previous research, we hypothesized that engineered expression of the
      baculovirus anti-apoptotic p35 gene might reduce symptoms of these diseases.
      Using Agrobacterium tumefaciens-mediated transformation of a cultivar highly
      susceptible to several pathogens, 14 independent NLL lines containing both the
      p35 and bar genes were obtained (p35-NLL). Integration and expression of the
      transgenes were confirmed by polymerase chain reaction (PCR), progeny testing,
      Southern blot, Northern blot and reverse transcriptase-PCR analyses. Fecundity
      and nodulation were not altered in these lines. Third or fourth generation p35
      NLL lines were challenged with necrotrophic fungal pathogens (anthracnose in stem
      and leaf, and Pleiochaeta root rot and leaf brown spot) in controlled environment
      conditions. Several p35-NLL lines had significantly reduced disease symptoms.
      Interestingly, as with natural resistance, no single line was improved for all
      three diseases which possibly reflecting spatial variation of p35 expression in
      planta. These data support an alternative molecular definition for 'necrotrophic
      disease' in plants and suggest new routes for achieving resistance against a
      range of pathogens.

PMID- 19754838
TI  - Engineering OsBAK1 gene as a molecular tool to improve rice architecture for high
      yield.
AB  - Generating a new variety of plant with erect-leaf is a critical strategy to
      improve rice grain yield, as plants with this trait can be dense-planted. The
      erect-leaf is a significant morphological trait partially regulated by
      Brassinosteroids (BRs) in rice plants. So far, only a few genes can be used for
      molecular breeding in rice. Here, we identified OsBAK1 as a potential gene to
      alter rice architecture. Based on rice genome sequences, four closely related
      homologs of Arabidopsis BAK1 (AtBAK1) gene were amplified. Phylogenetic analysis
      and suppression of a weak Arabidopsis mutant bri1-5 indicated that OsBAK1
      (Os08g0174700) is the closest relative of AtBAK1. Genetic, physiological, and
      biochemical analyses all suggest that the function of OsBAK1 is conserved with
      AtBAK1. Overexpression of a truncated intracellular domain of OsBAK1, but not the
      extracellular domain of OsBAK1, resulted in a dwarfed phenotype, similar to the
      rice BR-insensitive mutant plants. The expression of OsBAK1 changed important
      agricultural traits of rice such as plant height, leaf erectness, grain
      morphologic features, and disease resistance responses. Our results suggested
      that a new rice variety with erect-leaf and normal reproduction can be generated
      simply by suppressing the expression level of OsBAK1. Therefore, OsBAK1 is a
      potential molecular breeding tool for improving rice grain yield by modifying
      rice architecture.

PMID- 19754839
TI  - Safener responsiveness and multiple herbicide resistance in the weed black-grass
      (Alopecurus myosuroides).
AB  - Safeners enhance the selectivity of graminicidal herbicides such as fenoxaprop
      ethyl in cereals, by increasing their rates of detoxification in the crop. While
      studying the selectivity of fenoxaprop ethyl in wheat, we determined that the
      safeners mefenpyr diethyl and fenchlorazole ethyl also enhanced herbicide
      tolerance in the competing weed black-grass (Alopecurus myosuroides). Fenoxaprop
      ethyl was detoxified by conjugation with glutathione in both wheat and black
      grass, with the resulting metabolites processed to the respective cysteine
      derivatives, which were then N-glycosylated. In black-grass, these detoxification
      pathways were only slightly enhanced by safeners, suggesting that metabolism
      alone was unlikely to account for increased herbicide tolerance. Instead, it was
      determined that safening was associated with an accumulation of glutathione and
      hydroxymethylglutathione and enzymes with antioxidant functions including phi and
      lambda glutathione transferases, active as glutathione peroxidases and thiol
      transferases respectively. These safener-induced changes closely mirrored those
      determined in two independent black-grass populations that had acquired multiple
      herbicide resistance (MHR) in the field. In addition to enhanced glutathione
      metabolism, both safener treatment and MHR resulted in elevated levels of
      flavonoids in the foliage of black-grass plants, notably flavone-C-glycosides and
      anthocyanins. Our results demonstrate that safening in a grass weed is associated
      with an inducible activation in antioxidant and secondary metabolism which
      mirrors the biochemical phenotype exhibited in plants that are resistant to
      multiple classes of herbicides.

PMID- 19754840
TI  - ZFN-induced mutagenesis and gene-targeting in Arabidopsis through Agrobacterium
      mediated floral dip transformation.
AB  - Zinc-finger nucleases (ZFNs) are artificial restriction enzymes, custom designed
      for induction of double-strand breaks (DSBs) at a specific locus. These DSBs may
      result in site-specific mutagenesis or homologous recombination at the repair
      site, depending on the DNA repair pathway that is used. These promising
      techniques for genome engineering were evaluated in Arabidopsis plants using
      Agrobacterium-mediated floral dip transformation. A T-DNA containing the target
      site for a ZFN pair, that was shown to be active in yeast, was integrated in the
      Arabidopsis genome. Subsequently, the corresponding pair of ZFN genes was stably
      integrated in the Arabidopsis genome and ZFN activity was determined by PCR and
      sequence analysis of the target site. Footprints were obtained in up to 2% of the
      PCR products, consisting of deletions ranging between 1 and 200 bp and insertions
      ranging between 1 and 14 bp. We did not observe any toxicity from expression of
      the ZFNs. In order to obtain ZFN-induced gene-targeting (GT), Arabidopsis plants
      containing the target site and expressing the ZFN pair were transformed with a T
      DNA GT construct. Three GT plants were obtained from approximately 3000
      transformants. Two of these represent heritable true GT events, as determined by
      PCR, Southern blot analysis and sequencing of the resulting recombined locus. The
      third plant showed an ectopic GT event. No GT plants were obtained in a
      comparable number of transformants that did not contain the ZFNs. Our results
      demonstrate that ZFNs enhance site-specific mutagenesis and gene-targeting of
      Agrobacterium T-DNA constructs delivered through floral dip transformation.

PMID- 19754841
TI  - The national registry of haemophilia A and B in Spain: results from a census of
      patients.

PMID- 19754842
TI  - VERITAS-PRN: a new measure of adherence to episodic treatment regimens in
      haemophilia.
AB  - Episodic treatment of bleeding disorders is defined as utilization of clotting
      factor concentrates in response to acute bleeding episodes to achieve
      haemostasis. Non-adherence to prescribed episodic regimens can limit treatment
      effectiveness and result in target joint formation, pain and disability.
      Evaluation of and interventions to promote adherence may improve health outcomes.
      The purpose of this study was to validate a new adherence scale developed for
      individuals with bleeding disorders treated on episodic infusion regimens,
      entitled VERITAS-PRN [Validated Hemophilia Regimen Treatment Adherence Scale -
      PRN]. Participants were recruited from the Indiana Hemophilia and Thrombosis
      Center patient population. Participants completed the scale for psychometric
      development and analysis. Subjective ratings of adherence from participants and
      providers were used for validation. The study sample included 51 male and three
      female patients. Twenty-seven participants (50.0%) were diagnosed with FVIII
      deficiency, 21 (38.9%) with FIX deficiency and six (11.1%) with von Willebrand's
      disease (VWD). Internal consistency reliability for the total VERITAS-PRN score
      and the majority of subscales was good-to-excellent, with the one exception being
      the 'Plan' subscale. Test-retest reliability correlations were good-to-excellent
      for the total scale and all subscales. The VERITAS-PRN total scale had moderate
      to-strong and statistically significant correlations with validity measures. The
      VERITAS-PRN is a reliable and valid measure of adherence to episodic treatment
      regimens for bleeding disorders. This tool may be utilized as a standard measure
      of adherence to increase sensitivity to adherence problems and promote targeted
      interventions to enhance adherence and health outcomes.

PMID- 19754843
TI  - The sustainable pumping rate concept: lessons from a case study in central Italy.
AB  - The term sustainable pumping rate (SPR) is defined as the maximum pumping rate
      that can be maintained indefinitely without mining an aquifer, and is different
      from the concept of safe yield (SY), which takes into account also aspects
      related to the much wider concept of sustainability. The assessment of the SPR
      for the case study of Petrignano d'Assisi, an alluvial aquifer located in Central
      Italy, shows the need for a reliable estimate of the global water budget of the
      aquifer, particularly of the recharge under undisturbed conditions; however, the
      latter is not sufficient, because the SPR is affected also by the geometry of the
      aquifer, the hydraulic conductivity pattern, the variation of recharge/discharge
      ratio induced by the abstractions, and so on. All these aspects are analyzed by
      means of a numerical flow model calibrated both under undisturbed conditions
      (1974) and under exploitation conditions (1998 to 2004). The steady-state
      modeling results show that the relation between recharge and abstractions both at
      local and global scale is a key point in order to estimate a long-term SPR.
      Moreover, as it could be necessary to overexploit the aquifer for short periods,
      e.g., during drought episodes, the estimate of SPR must be performed also in
      transient conditions, in order to take into account the characteristic time of
      depletion and the successive recovery.

PMID- 19754845
TI  - Models and model analysis.

PMID- 19754846
TI  - Ancient Greek geographer Pausanias as a qualitative karst hydrogeologist.

PMID- 19754847
TI  - Retraction. A single recovery type curve from Theis' exact solution.

PMID- 19754848
TI  - Origin and extent of fresh paleowaters on the Atlantic continental shelf, USA.
AB  - While the existence of relatively fresh groundwater sequestered within permeable,
      porous sediments beneath the Atlantic continental shelf of North and South
      America has been known for some time, these waters have never been assessed as a
      potential resource. This fresh water was likely emplaced during Pleistocene sea
      level low stands when the shelf was exposed to meteoric recharge and by elevated
      recharge in areas overrun by the Laurentide ice sheet at high latitudes. To test
      this hypothesis, we present results from a high-resolution paleohydrologic model
      of groundwater flow, heat and solute transport, ice sheet loading, and sea level
      fluctuations for the continental shelf from New Jersey to Maine over the last 2
      million years. Our analysis suggests that the presence of fresh to brackish water
      within shallow Miocene sands more than 100 km offshore of New Jersey was
      facilitated by discharge of submarine springs along Baltimore and Hudson Canyons
      where these shallow aquifers crop out. Recharge rates four times modern levels
      were computed for portions of New England's continental shelf that were overrun
      by the Laurentide ice sheet during the last glacial maximum. We estimate the
      volume of emplaced Pleistocene continental shelf fresh water (less than 1 ppt) to
      be 1300 km(3) in New England. We also present estimates of continental shelf
      fresh water resources for the U.S. Atlantic eastern seaboard (10(4) km(3)) and
      passive margins globally (3 x 10(5) km(3)). The simulation results support the
      hypothesis that offshore fresh water is a potentially valuable, albeit
      nonrenewable resource for coastal megacities faced with growing water shortages.

PMID- 19754849
TI  - Large-scale mapping of hard-rock aquifer properties applied to Burkina Faso.
AB  - A country-scale (1:1,000,000) methodology has been developed for hydrogeologic
      mapping of hard-rock aquifers (granitic and metamorphic rocks) of the type that
      underlie a large part of the African continent. The method is based on
      quantifying the "useful thickness" and hydrodynamic properties of such aquifers
      and uses a recent conceptual model developed for this hydrogeologic context. This
      model links hydrodynamic parameters (transmissivity, storativity) to lithology
      and the geometry of the various layers constituting a weathering profile. The
      country-scale hydrogeological mapping was implemented in Burkina Faso, where a
      recent 1:1,000,000-scale digital geological map and a database of some 16,000
      water wells were used to evaluate the methodology.

PMID- 19754850
TI  - Characterization of 20 single nucleotide polymorphism markers in the Pacific
      oyster (Crassostrea gigas).

PMID- 19754851
TI  - Establishment of a strain inheriting a sex-linked SNP marker in Patagonian
      pejerrey (Odontesthes hatcheri), a species with both genotypic and temperature
      dependent sex determination.
AB  - The Patagonian pejerrey Odontesthes hatcheri is an atherinopsid species
      presenting genotypic sex determination (GSD) at intermediate temperatures and
      temperature-dependent sex determination at the low and high ranges of thermal
      tolerance. A recent study revealed the presence of a sex-linked SNP marker in
      some males of this species, but a strain which inherits the marker faithfully has
      not been established. This research was conducted to develop such a strain, for
      use as a tool to study the molecular mechanisms of gonadal sex differentiation
      and sexual dimorphism, and to obtain basic information on the GSD mode in this
      species. For these purposes, we performed backcrosses and full-sibling crosses
      using males and females whose presumptive genotypic sex was inferred from the
      presence of the sex-linked SNP marker. Four backcrosses between SNP(-) daughters
      and their SNP(+) father generated balanced sex ratios with the phenotypic sex
      matching the genotypic sex in most cases (98.21%) at an intermediate, sexually
      neutral temperature (21 degrees C). Full-sibling crosses between these four SNP(
      ) females and their SNP(+) brothers produced three progenies with balanced sex
      ratios and one with 94.4% males. The results of this study confirm that a strain
      inheriting the sex-linked SNP marker was successfully developed. Moreover, the
      inheritance pattern of the marker and the sex ratios of the progenies provide
      strong evidence that the GSD mode in O. hatcheri is the XX-XY system.

PMID- 19754852
TI  - Genetic parameters for guiding ability in purpose bred dogs.

PMID- 19754853
TI  - Effects of atorvastatin on circulating CD34+/CD133+/ CD45- progenitor cells and
      indices of angiogenesis (vascular endothelial growth factor and the angiopoietins
      1 and 2) in atherosclerotic vascular disease and diabetes mellitus.
AB  - BACKGROUND: Cardiovascular disease (CVD) remains a major cause of morbidity and
      mortality, especially in the presence of diabetes, possibly because of
      endothelial damage. Increased circulating progenitor cells (CPCs) and increased
      plasma markers of angiogenesis [vascular endothelial growth factor (VEGF) and the
      angiopoietins (Ang-1 and -2)] may be evidence of this damage. Treatment with
      hydroxy-methyl-glutaryl (HMG-CoA) reductase inhibitors ('statins') improves
      outcomes in patients with vascular disease, including diabetic patients. We
      hypothesized that 80 mg per day atorvastatin influences CPC counts of VEGF and
      the angiopoietins in patients with atherosclerotic CVD with or without diabetes
      mellitus. METHODS: Cardiovascular disease patients with diabetes mellitus (Group
      A, n = 14) and nondiabetic patients with CVD only (Group B, n = 10) took
      atorvastatin 80 mg per day for a period of 8-10 weeks. CPCs (CD34+/CD133+/CD45-)
      were defined by flow cytometry, plasma levels VEGF and Ang-1 and Ang-2 by ELISA).
      RESULTS: Circulating progenitor cell counts increased (P < 0.001) in Group A
      compared with a nonsignificant change in Group B (P = 0.37). VEGF levels fell
      significantly in Group A (P = 0.04) but no significant change was seen in Group B
      (P = 0.16). Whilst Ang-1 remained unchanged (P = 0.41), Ang-2 levels increased
      markedly in both groups (P < 0.05). These effects were independent of LDL and
      total cholesterol changes but were associated with HDL changes. CONCLUSION: High
      dose atorvastatin increased circulating CPCs, reduced VEGF and increased Ang-2 in
      patients with diabetes and CVD, providing another possible pathophysiological
      mechanism for the beneficial effects of statins in CVD.

PMID- 19754854
TI  - Vaccinate your child and save its grandparents from a heart attack? Current
      perspectives in antipneumococcal vaccination.
AB  - Streptococcus pneumoniae is an important cause of morbidity and mortality
      worldwide. There are three established approaches to anti-pneumococcal
      vaccination: capsular polysaccharide pneumococcal vaccine (PPV), protein
      polysaccharide conjugate pneumococcal vaccine (CPV) and protein-based
      pneumococcal vaccine (PBPV). At present, only a 23-valent PPV for use in adults
      and a seven-valent CPV for use in infants are available in clinical practice.
      This study reviews available data on the efficacy of the available vaccines in
      different age groups and disease presentations, and the advantages and
      shortcomings of each type of vaccine, including future perspectives. Special
      attention is given to controversies regarding the efficacy of PPV against
      pneumonia in adults and its protective effects against myocardial infarction.

PMID- 19754855
TI  - Follow-ups of the Cardiovascular Risk in Young Finns Study in 2001 and 2007:
      levels and 6-year changes in risk factors.
AB  - OBJECTIVES: To examine cardiovascular risk factor levels in 2007 and their 6-year
      changes between 2001 and 2007 using the data collected in the follow-ups of the
      Cardiovascular Risk in Young Finns Study. DESIGN: Population-based follow-up
      study. SUBJECTS: A total of 2204 healthy Finnish adults aged 30-45 years (1210
      women; 994 men). MAIN OUTCOME MEASURES: Levels in 2007 and changes between 2001
      and 2007 of lipids, insulin, glucose, blood pressure, smoking, body mass index,
      alcohol consumption, waist and hip circumferences. RESULTS: The mean serum total
      cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein
      (HDL) cholesterol and triglyceride concentrations in 30- to 45-year-old adults
      were 5.05, 3.09, 1.34 and 1.40 mmol L(-1), respectively. Significant changes (P <
      0.05) between 2001 and 2007 in 30- to 39-year-old subjects included a decrease in
      total cholesterol (-6.6% in men, -5.8% in women), LDL-cholesterol (-10.2% and 
      11.6%) and an increase in diastolic blood pressure (3.5% and 3.9%). Waist
      circumference (1.8% and 5.5%) and systolic blood pressure increased in 36-39 year
      olds (2.3% and 2.3%). HDL-cholesterol increased in 30- to 33-year-old women
      (5.8%) Glucose levels increased in 30- to 39-year-old women (3.7%) and 36- to 39
      year-old men (3.6%). Smoking prevalence decreased in 36- to 39-year-old men from
      29.8% to 22.2%. CONCLUSIONS: The 6-year changes in total cholesterol, LDL
      cholesterol and HDL-cholesterol in young Finns were favourable between 2001 and
      2007. However, waist circumference, glucose and blood pressure levels increased.
      Therefore, continuous efforts are still needed in fighting against cardiovascular
      risk factors.

PMID- 19754856
TI  - An investigation of serum concentration of apoM as a potential MODY3 marker using
      a novel ELISA.
AB  - OBJECTIVE: To investigate the fitness of serum apolipoprotein M (apoM)
      concentration as a marker for maturity-onset diabetes of the young 3 (MODY3).
      STUDY DESIGN AND SUBJECTS: This study consisted of two parts. A family study
      included 71 carriers of the P291fsinsC mutation in hepatocyte nuclear factor
      1alpha (HNF-1alpha) from the Finnish Botnia study, 53 of whom were diabetic, and
      75 matched family controls. A second, case-control study included 24 MODY3
      patients, 17 healthy MODY3 mutation carriers, 11 MODY1 patients, 18 type 2
      diabetes patients and 19 healthy control individuals. Subjects in the case
      control study were recruited from the Botnia study or the Clinic of
      Endocrinology, Malmo University Hospital. Serum apoM levels were measured using a
      novel ELISA based on two monoclonal apoM antibodies. RESULTS: In the family
      study, mean serum apoM was 10% lower in female carriers of the P291fsinsC
      mutation compared to the family controls (P = 0.0058), a difference which
      remained significant after adjustment for diabetes status. There was no observed
      difference between groups for men. In the case-control study, no significant
      difference in apoM concentration was observed between MODY3 and type 2 diabetes
      patients, neither before nor after adjustment for total cholesterol. CONCLUSIONS:
      Female carriers of the P291fsinsC mutation in HNF-1alpha displayed slightly lower
      apoM serum levels. This difference is too small for apoM to be reliably employed
      as a biomarker for HNF-1alpha mutation status.

PMID- 19754857
TI  - Clinical significance of low-grade renal artery stenosis.
AB  - BACKGROUND: Patients with a renal artery stenosis (RAS) >50% carry an increased
      risk for future cardiovascular (CV) events. Experimental literature on this topic
      suggests that this might as well be true for subjects with lower-grade RAS.
      METHODS: Recruitment in this longitudinal cohort study was conducted from 1982 to
      2002 in a Dutch University Hospital. Included in this study were 301 hypertensive
      patients clinically suspected of having RAS. Study participants were
      radiologically classified as having no, a low-grade (<50% lumen narrowing) or
      high-grade (> or =50%) RAS. A predetermined composite CV end-point was defined as
      one of the following: myocardial infarction or 'objectified' angina pectoris,
      ischaemic stroke or death from any CV cause. Other end-points were the occurrence
      of CV complications, all-cause plus CV mortality and decline in renal function.
      RESULTS: During a median follow-up of 8.2 years, the incidence of the composite
      end-point totalled 79 events. After full adjustment in Cox models, a significant
      risk increase in high-grade [hazard ratio (HR) 2.81; P = 0.002] and low-grade RAS
      (HR 2.32; P = 0.038) was observed. Other end-points did not differ significantly
      between study groups. CONCLUSION: Hypertensive subjects with RAS of any extent,
      compared with hypertensives without RAS, carry a substantially increased risk for
      future CV events. Therefore, even in patients with low-grade RAS, aggressive
      pharmacological treatment strategies should be adopted as a preventive measure.

PMID- 19754858
TI  - A functional variant in the gene 3' untranslated region regulates HSP70
      expression and is a potential candidate for insulin resistance-related
      abnormalities.

PMID- 19754859
TI  - Immunohistochemical and biomolecular identification of orphanin FQ, eNOS, atrial
      natriuretic factor and oxytocin in rat seminal vesicles.
AB  - In previous studies performed on rodents, we detected the presence of adreno
      cholinergic and peptidergic innervation in seminal vesicles and other organs of
      the male genital system, such as prostate and deferent duct, in which we also
      investigated the expression of NOS and NADPH-diaphorase. During this project, we
      focused our attention on the expression of some peptides involved in local
      control of smooth muscle relaxation, contractility, vasodilatation and control of
      blood flow in rat seminal vesicles. We investigated, through immunohistochemistry
      and RT-PCR, the presence of four peptides: orphanin, eNOS, ANF and oxytocin.
      Immunohistochemistry was used to detect the presence of the proteins, whereas RT
      PCR analysis confirmed gene expression of orphanin, eNOS and ANF, but not
      oxytocin. In our opinion, orphanin, eNOS and ANF could have paracrine effects
      regulating the function of seminal vesicles, whereas oxytocin, which may reach
      this anatomical district through the blood flow, may have a hormonal action. This
      is a pilot study that, with further investigation, may allow to better clarify
      the role of these molecules in the control of seminal vesicle tissues'
      homeostasis.

PMID- 19754860
TI  - The prenatal development and histochemistry of the ileal mucins in the bovine
      fetuses.
AB  - Few studies exist regarding the distribution of intestinal mucins in fetuses of
      mammalians such as cattle and sheep. In this study, we aimed to describe the
      changes in the mucin production by ileal epithelium of bovine fetuses during
      their prenatal development. The goblet cells showed heterogeneity in mucins and
      the apical cytoplasm of the enterocytes demonstrated Periodic acid Schiff
      positive reaction which declined gradually towards the birth. Moreover, the
      number of the goblet cells containing acidic and mixed mucins augmented, whereas
      those containing neutral mucins decreased with advancing gestational age. After
      sixth month of gestation, with the initiation of the ileal Peyer patches and
      follicle-associated epithelium development, a gradual increase in the number of
      goblet cells containing sulfomucins was also noticed towards the birth. The
      presence of different mucins in the ileum of bovine fetuses throughout prenatal
      development might play a role in the protection of the intestinal mucosa against
      urinary waste products in swallowed amniotic fluid and bile. Furthermore, mucins
      can also contribute for the formation of meconium in intra-uterine life and
      building of strong intestinal barrier with predominating sulfomucins, protecting
      the intestine against potential pathogens and digestive enzymes after birth.

PMID- 19754861
TI  - Emergency medicine and political influence.
AB  - The 2008 election brought sweeping political change to Washington, DC. For a
      variety of reasons, there is also substantial political momentum for reform of
      our health care system. At the 2008 Association of American Medical Colleges
      meeting in San Antonio, Texas, the Association of Academic Chairs of Emergency
      Medicine, meeting in conjunction with the Society for Academic Emergency
      Medicine, chose to examine the topic of "advocacy and political influence." This
      article summarizes comments made at the meeting and develops the argument that
      expertise in health policy and political advocacy are valuable skills that should
      be considered legitimate components of scholarly activity in academic emergency
      medicine. Strategies for effective advocacy of issues relevant to emergency
      medicine and emergency patient care are also discussed.

PMID- 19754862
TI  - A method for improving arrival-to-electrocardiogram time in emergency department
      chest pain patients and the effect on door-to-balloon time for ST-segment
      elevation myocardial infarction.
AB  - OBJECTIVES: The objectives were to determine if an emergency department (ED)
      could improve the adherence to a door-to-electrocardiogram (ECG) time goal of 10
      minutes or less for patients who presented to an ED with chest pain and the
      effect of this adherence on door-to-balloon (DTB) time for ST-segment elevation
      myocardial infarction (STEMI) cardiac catheterization (cath) alert patients.
      METHODS: This was a planned 1-month before-and-after interventional study design
      for implementing a new process for obtaining ECGs in patients presenting to the
      study ED with chest pain. Prior to the change, patients were registered and
      triaged before an ECG was obtained. The new procedure required registration
      clerks to identify those with chest pain and directly overhead page or call a
      designated ECG technician. This technician had other ED duties, but prioritized
      performing ECGs and delivering them to attending physicians. A full registration
      process occurred after the clinical staff performed their initial assessment. The
      primary outcome was the total percentage of patients with chest pain who received
      an ECG within 10 minutes of ED arrival. The secondary outcome was DTB time for
      patients with STEMI who were emergently cath alerted. Data were analyzed using
      mean differences, 95% confidence intervals (CIs), and relative risk (RR)
      regression to adjust for possible confounders. RESULTS: A total of 719 patients
      were studied: 313 before and 405 after the intervention. The mean (+/-standard
      deviation [SD]) age was 50 (+/-16) years, 54% were women, 57% were African
      American, and 36% were white. Patients walked in 89% of the time; 11% arrived by
      ambulance. Thirty-nine percent were triaged as emergent and 61% as nonemergent.
      Patients presented during daytime 68% of the time, and 32% presented during the
      night. Before the intervention, 16% received an ECG at 10 minutes or less. After
      the intervention, 64% met the time requirement, for a mean difference of 47.3%
      (95% CI = 40.8% to 53.3%, p < 0.0001). Results were not affected by age, sex,
      race, mode of arrival, triage classification, or time of arrival. For patients
      with STEMI cath alerts, four were seen before and seven after the intervention.
      No patients before the intervention had ECG time within 10 minutes, and one of
      four had DTB time of <90 minutes. After the intervention, all seven patients had
      ECG time within 10 minutes; the three arriving during weekday hours when the cath
      team was on site had DTB times of <90 minutes, but the four arriving at night and
      on weekends when the cath team was off site had DTB times of >90 minutes.
      CONCLUSIONS: The overall percentage of patients with a door-to-ECG time within 10
      minutes improved without increasing staffing. An ECG was performed within 10
      minutes of arrival for all patients who were STEMI cath alerted, but DTB time
      under 90 minutes was achieved only when the cath team was on site.

PMID- 19754863
TI  - Increased D-dimer concentration in plasma of patients with severe acute
      urticaria.

PMID- 19754864
TI  - Etanercept and infections.

PMID- 19754865
TI  - Targeted broadband ultraviolet B phototherapy improves disorders characterized by
      increased dermal matrix.

PMID- 19754866
TI  - Pigmented reticular structures in basal cell carcinoma and collision tumours.
AB  - BACKGROUND: The dermatoscopic diagnosis of basal cell carcinoma (BCC) is based on
      well-known specific criteria. Despite the fact that a pigment network is
      considered a negative feature for the diagnosis of BCC, its detection in a BCC
      context has been reported in 2.8% of cases. OBJECTIVES: To determine whether
      pigment networks or network-like structures might represent a pitfall for the
      correct diagnosis of BCC. METHODS: Dermatoscopic images of 412
      histopathologically proven BCCs were analysed retrospectively. RESULTS: Pigment
      network or network-like structures were detected in 14 of 412 (3.4%) BCCs. Nine
      of 14 BCCs presented a typical pigment network, due to the association of a BCC
      lesion with a naevus, solar lentigo or actinic keratosis; two BCCs located on the
      face showed a pseudonetwork, and three of 14 lesions displayed a network-like
      structure characterized by light-brown irregularly meshed short linear
      structures, histopathologically related to a hyperpigmentation of the basal layer
      of the epidermis. CONCLUSIONS: The presence of a pigment network in the context
      of a BCC is uncommon, and it usually reflects the association of BCC with a solar
      lentigo, naevus or a specific location of the lesion on photodamaged skin.

PMID- 19754867
TI  - Health-related utility among adults with atopic dermatitis treated with 0.1%
      tacrolimus ointment as maintenance therapy over the long term: findings from the
      Protopic CONTROL study.
AB  - BACKGROUND: Long-term maintenance treatment with 0.1% tacrolimus ointment for the
      prevention of flares has been demonstrated to be well tolerated and effective in
      adults for the treatment of atopic dermatitis (AD) but its impact on health
      related utility has not been reported. OBJECTIVES: The purpose of this study was
      to estimate utility changes associated with the use of tacrolimus ointment in the
      maintenance treatment of adults with AD. METHODS: Data were collected from a
      clinical trial investigating long-term maintenance treatment with 0.1% tacrolimus
      ointment in adults with AD. All patients were treated with twice-daily tacrolimus
      ointment during an open-label period (OLP) of up to 6 weeks, with subsequent
      randomization to a double-blind disease-control period (DCP) of 12 months
      comparing tacrolimus ointment, used twice weekly as maintenance treatment, vs.
      the emollient vehicle as standard treatment. Health-related utility (EQ
      5D(index)) was estimated by Monte Carlo simulation from SF-12 responses by
      application of a published response mapping algorithm and the U.K. tariff for EQ
      5D responses and SF-6D responses, respectively. RESULTS: Evaluable data were
      available for 257 patients stratified into mild, moderate or severe AD with a
      median age at screening of 28 years [interquartile range (IQR) 22-38] and 40%
      male. At screening the median EQ-5D(index) across the strata was 0.848 units (IQR
      0.704-0.882) for mild cases, 0.796 (0.737-0.876) for moderate cases, and 0.760
      (0.661-0.823, P < 0.001) for those with severe disease. At the end of the OLP,
      mean utility improvement across all strata was 0.027 [95% confidence interval
      (CI) -0.011 to 0.065, P = 0.165] for mild cases, 0.046 (95% CI 0.015-0.064, P =
      0.002) for moderate cases and 0.076 (95% CI 0.035-0.118, P < 0.001) for those
      with severe disease. At the end of the blinded DCP, repeated measures analysis
      showed an age- and sex-adjusted mean change of 0.045 units (P < 0.001) for
      subjects treated with tacrolimus ointment over those treated with emollient
      vehicle. CONCLUSIONS: Patients with AD of all severities showed considerable
      decrements in health-related utility. However, treatment with 0.1% tacrolimus
      ointment was associated with clinically significant improvement in health-related
      utility for patients with moderate and severe AD, which was sustained over a 12
      month maintenance period compared with those using standard treatment with an
      emollient vehicle.

PMID- 19754868
TI  - Antimicrobial susceptibility of Staphylococcus aureus isolated from children with
      impetigo in China from 2003 to 2007 shows community-associated methicillin
      resistant Staphylococcus aureus to be uncommon and heterogeneous.
AB  - BACKGROUND: The number of patients with impetigo caused by community-associated
      methicillin-resistant Staphylococcus aureus (CA-MRSA) has been increasing.
      OBJECTIVES: To investigate the antimicrobial susceptibility of S. aureus causing
      impetigo in children in China from 2003 to 2007 and further characterize isolates
      of CA-MRSA. MATERIALS AND METHODS: We examined 984 S. aureus isolates for
      antimicrobial susceptibility to 11 antimicrobials using the agar dilution method.
      CA-MRSA isolates were analysed for Panton-Valentine leucocidin (PVL) genes, and
      staphylococcal cassette chromosome mec (SCCmec) typing was performed. RESULTS:
      The largest proportion (94.5%) of strains were resistant to penicillin, followed
      by erythromycin (86.2%) and clindamycin (69.6%). In total 772 of 984 (78.5%) S.
      aureus strains were multiresistant. The incidence of CA-MRSA was 1.1%, with a
      high rate of resistance to clindamycin (90.9%) and tetracycline (72.7%), but all
      were susceptible to ciprofloxacin. The susceptibility profiles of MRSA to other
      antimicrobial agents were similar to those of methicillin-sensitive S. aureus
      (MSSA). None of the S. aureus strains were resistant to vancomycin and fusidic
      acid; moreover, only one strain was resistant to mupirocin. Typing of the SCCmec
      showed that 54.5% were type IV, 18.2% were type V and 9.1% were type VI. All the
      PVL-positive CA-MRSA carried SCCmec type IV. CONCLUSIONS: CA-MRSA is still
      relatively uncommon and heterogeneous in children in China. Penicillin and
      erythromycin are no longer appropriate agents. Effective antibiotic agents for
      patients with impetigo are mupirocin and fusidic acid.

PMID- 19754869
TI  - Trichothiodystrophy and fragile hair: the distinction between diagnostic signs
      and diagnostic labels in childhood hair disease.
AB  - BACKGROUND: Hair typically becomes fragile when there are structural
      abnormalities and/or a reduction in the sulphur-containing amino acids cystine or
      methionine. This finding in the setting of a neuroectodermal complaint is usually
      labelled trichothiodystrophy (TTD). The spectrum of features within this
      diagnostic grouping tests the validity of using sulphur-deficient hair as a
      central characteristic. OBJECTIVES: To determine what diagnoses were found within
      a group of subjects with fragile hair and whether low cystine or methionine were
      relevant central characteristics. METHODS: We examined cases referred to us from
      12 U.K. centres for hair microscopy over 10 years where hair fragility or
      clinical characteristics raised the possibility of TTD. All samples underwent
      amino acid analysis. This was achieved through cation exchange chromatography
      coupled with spectrophotometric quantification. RESULTS: Twenty-five patients (11
      male, 14 female) with a mean age of 11 years (0.3-37) were evaluated. Nineteen
      patients had features of hair damage. Of these, five patients had abnormalities
      on microscopy only and four patients had microscopic changes and tiger-tail
      pattern but normal amino acid content. The remaining 10 patients had reduced
      cystine content, two of whom also had low methionine. All but one had the tiger
      tail pattern. Among the wide range of phenotypes there were only three cases
      matching a diagnosis of TTD. CONCLUSIONS: Our data suggest that clinically
      apparent fragile hair in childhood is only rarely associated with a diagnosis of
      TTD. The tiger-tail change is sensitive but not wholly specific to TTD. We
      propose that the term trichothiodystrophy be limited in its use to define sulphur
      deficient hair rather than as a diagnostic term in a heterogeneous and incoherent
      multisystem disorder, where sulphur-deficient hair is one feature.

PMID- 19754870
TI  - Levetiracetam monotherapy for childhood occipital epilepsy of gastaut.
AB  - OBJECTIVES: The aim of this open label pilot study was to evaluate the efficacy
      and tolerability of levetiracetam (LEV) as 'de novo' monotherapy in children and
      adolescents with late onset childhood occipital epilepsy-Gastaut type (COE-G).
      MATERIAL AND METHODS: Twelve patients suffering from COE-G were enrolled in this
      prospective study. The age of seizures onset ranged from 6.1 to 16.2 years with a
      peak of frequency at mean (+/-SD) 10.54 +/- 2.77 years. Therapy with LEV was
      started at 10 mg/kg/day and, after titration, the final dose was generally
      achieved within 4 weeks and ranged from 20.7 to 45.2 mg/kg/day. RESULTS: At the 6
      month evaluation, 11 (91.6%) of the 12 patients studied were seizure free, and
      one (8.3%) showed four additional episodes. Electroencephalography (EEG) activity
      was normal in six (54.5%) patients, unchanged in two (18.1%) children, and in
      four (33.3%) patients sporadic occipital abnormalities persisted. At the 12-month
      evaluation all patients were completely seizure free. Four patients (33.3%)
      continued to show some EEG abnormalities, while eight (72.8%) patients had normal
      EEG. At the 18-month evaluation all patients were seizure free and 10 patients
      (83.3%) showed a complete normalization of EEG abnormalities. DISCUSSION:
      Monotherapy with LEV was effective and well tolerated in patients with COE-G.
      Nevertheless, prospective, large, long-term double-blind studies are needed to
      confirm these findings.

PMID- 19754871
TI  - Mechanisms of obesity and related pathologies: androgen deficiency and
      endothelial dysfunction may be the link between obesity and erectile dysfunction.
AB  - Obesity is associated with a high prevalence of erectile dysfunction; however,
      the pathophysiological link between obesity and erectile dysfunction remains
      poorly understood. In this minireview, we have attempted to evaluate the existing
      literature pertaining to obesity and erectile dysfunction to determine whether a
      common pathophysiological link exists. Visceral obesity is associated with
      increased inflammatory responses, which contribute to endothelial dysfunction.
      Furthermore, obesity is also associated with reduced plasma testosterone levels,
      which contributes to hypogonadism and increases the risk of vascular pathology.
      Endothelial dysfunction and androgen deficiency have previously been linked to
      the pathophysiological mechanisms of erectile dysfunction. The underlying
      pathophysiological mechanisms of endothelial dysfunction and testosterone
      deficiency include penile vascular insufficiency as a result of the loss of
      nitric oxide synthase expression and activity and the loss of tissue compliance,
      resulting in reduced hemodynamic properties. Recent progress in the field of
      sexual medicine has recognized the impact of vascular disease and hypogonadism on
      the management of patients with erectile dysfunction. We suggest that visceral
      obesity, a component of the metabolic syndrome, adversely affects endothelial
      function and testosterone levels, contributing to hypogandism and erectile
      dysfunction. Thus, clinical screening for the risk of erectile dysfunction in
      obese patients should include the assessment of waist circumference, testosterone
      levels, body mass index and physical inactivity.

PMID- 19754872
TI  - Mechanisms of obesity and related pathology: linking immune responses to
      metabolic stress.
AB  - There is a tightly regulated interaction, which is well-conserved in evolution,
      between the metabolic and immune systems that is deranged in states of over- or
      under-nutrition. Obesity, an energy-rich condition, is characterized by the
      activation of an inflammatory process in metabolically active sites such as
      adipose tissue, liver and immune cells. The consequence of this response is a
      sharp increase in circulating levels of proinflammatory cytokines, adipokines and
      other inflammatory markers. Activation of the immune response in obesity is
      mediated by specific signaling pathways, with Jun N-terminal kinase and IkappaB
      kinase beta/nuclear factor kappa-light-chain-enhancer of activated B cells being
      the most well studied. It is known that the above events modify insulin signaling
      and result in the development of insulin resistance. The nutrient overload
      characterizing obesity is a metabolic stressor associated with intracellular
      organelle (e.g. the endoplasmic reticulum) stress. The exact characterization of
      the series of events and the mechanisms that integrate the inflammatory response
      with metabolic homeostasis at the cellular and systemic level is a very active
      research field. In this minireview, we discuss the signaling pathways and
      molecules associated with the development of obesity-induced inflammation, as
      well as the evidence that supports a critical role for the stress response in
      this process.

PMID- 19754873
TI  - Mechanisms of obesity and related pathologies: the macro- and microcirculation of
      adipose tissue.
AB  - Adipose tissue is an endocrine organ made up of adipocytes, various stromal
      cells, resident and infiltrating immune cells, and an extensive endothelial
      network. Adipose secretory products, collectively referred to as adipokines, have
      been identified as contributors to the negative consequences of adipose tissue
      expansion that include cardiovascular disease, diabetes and cancer. Systemic
      blood circulation provides transport capabilities for adipokines and fuels for
      proper adipose tissue function. Adipose tissue microcirculation is heavily
      impacted by adipose tissue expansion, some adipokines can induce endothelial
      dysfunction, and angiogenesis is necessary to counter hypoxia arising as a result
      of tissue expansion. Tumors, such as invasive lesions in the mammary gland, co
      opt the adipose tissue microvasculature for local growth and metastatic spread.
      Lymphatic circulation, an area that has received little metabolic attention,
      provides an important route for dietary and peripheral lipid transport. We review
      adipose circulation as a whole and focus on the established and potential
      interplay between adipose tissue and the microvascular endothelium.

PMID- 19754874
TI  - Mechanisms of obesity and related pathologies: transcriptional control of adipose
      tissue development.
AB  - Obesity and its associated disorders, including diabetes and cardiovascular
      disease, have now reached epidemic proportions in the Western world, resulting in
      dramatic increases in healthcare costs. Understanding the processes and metabolic
      perturbations that contribute to the expansion of adipose depots accompanying
      obesity is central to the development of appropriate therapeutic strategies. This
      minireview focuses on a discussion of the recent identification of molecular
      mechanisms controlling the development and function of adipose tissues, as well
      as how these mechanisms contribute to the regulation of energy balance in
      mammals.

PMID- 19754875
TI  - Mechanisms of obesity and related pathologies: role of apolipoprotein E in the
      development of obesity.
AB  - Apolipoprotein E is a polymorphic glycoprotein in humans with a molecular mass of
      34.5 kDa. It is a component of chylomicron remnants, very low density
      lipoprotein, low density lipoprotein and high density lipoprotein, and is
      primarily responsible for maintaining plasma lipid homeostasis. In addition to
      these well-documented functions, recent studies in experimental mouse models, as
      well as population studies, show that apolipoprotein E also plays an important
      role in the development of obesity and insulin resistance. It is widely accepted
      that disruption in homeostasis between food intake and energy expenditure, and
      the subsequent deposition of excess fatty acids into fat cells in the form of
      triglycerides, leads to the development of obesity. Despite the pivotal role of
      obesity and dyslipidemia in the development of the metabolic syndrome and heart
      disease, the functional interactions between adipose tissue and components of the
      lipoprotein transport system have not yet been investigated thoroughly. In this
      minireview, we focus on the current literature pertinent to the involvement of
      apolipoprotein E in the development of pathologies associated with the metabolic
      syndrome.

PMID- 19754876
TI  - Mechanisms of obesity and related pathologies.

PMID- 19754877
TI  - Hsp105beta upregulates hsp70 gene expression through signal transducer and
      activator of transcription-3.
AB  - Hsp105alpha and Hsp105beta are mammalian members of the Hsp105/110 family, a
      divergent subgroup of the Hsp70 family. Hsp105alpha is expressed constitutively
      and induced by various forms of stress, whereas Hsp105beta is an alternatively
      spliced form of Hsp105alpha that is expressed specifically during mild heat
      shock. In a report, it was shown that Hsp105alpha and Hsp105beta localize to the
      cytoplasm and of nucleus of cells, respectively, and that Hsp105beta, but not
      Hsp105alpha, induces the expression of Hsp70 in mammalian cells. Here, we
      examined the mechanism by which Hsp105beta induces the expression of Hsp70. Using
      a series of deletion mutants of Hsp105beta, it was revealed that the region
      between amino acids 642 and 662 of Hsp105beta is necessary for the activation of
      the hsp70 promoter by Hsp105beta. Furthermore, it was shown that signal
      transducer and activator of transcription (STAT)-3 bound to the sequence of the
      hsp70 promoter between -206 and -187 bp, and that mutations of this sequence
      abrogated the activation of the hsp70 promoter by Hsp105beta. In addition,
      overexpression of Hsp105beta stimulated the phosphorylation of STAT3 at Tyr705
      and its translocation to the nucleus. Downregulation of STAT3 expression resulted
      in reduction of the activation of the hsp70 promoter by Hsp105beta. Furthermore,
      downregulation of Hsp105beta reduced the expression of Hsp70 in heat-shocked
      cells. On the basis of these findings, it is suggested that Hsp105beta induces
      Hsp70 expression markedly through the STAT3 pathway in heat-shocked cells. This
      may represent the mechanism that connects the heat shock protein and STAT
      families for cell defense against deleterious stress.

PMID- 19754878
TI  - Ocular abnormalities in mice lacking the immunoglobulin superfamily member Cdo.
AB  - Vertebrate eye development requires a series of complex morphogenetic and
      inductive events to produce a lens vesicle centered within the bilayered optic
      cup and a posteriorly positioned optic stalk. Multiple congenital eye defects,
      including microphthalmia and coloboma, result from defects in early eye
      morphogenesis. Cdo is a multifunctional cell surface immunoglobulin superfamily
      member that interacts with and mediates signaling by cadherins and netrins to
      regulate myogenesis. In addition, Cdo plays an essential role in early forebrain
      development by functioning as coreceptor for sonic hedgehog. It is reported here
      that Cdo is expressed in a dynamic, but dorsally restricted, fashion during early
      eye development, and that mice lacking Cdo display multiple eye defects.
      Anomalies seen in Cdo(-/-) mice include coloboma (failure to close the optic
      fissure); failure to form a proper boundary between the retinal pigmented
      epithelium and optic stalk; defective lens formation, including failure to
      separate from the surface ectoderm; and microphthalmia. Consistent with this wide
      array of defects, developing eyes of Cdo(-/-) mice show altered expression of
      several regulators of dorsoventral eye patterning, including Pax6, Pax2, and
      Tbx5. Taken together, these findings show that Cdo is required for normal eye
      development and is required for normal expression of patterning genes in both the
      ventral and dorsal domains. The multiple eye development defects seen in Cdo(-/-)
      mice suggest that mutations in human Cdo could contribute to congenital eye
      anomalies, such as Jacobsen syndrome, which is frequently associated with ocular
      defects, including coloboma and Peters' anomaly.

PMID- 19754879
TI  - Disulfide bridge regulates ligand-binding site selectivity in liver bile acid
      binding proteins.
AB  - Bile acid-binding proteins (BABPs) are cytosolic lipid chaperones that play
      central roles in driving bile flow, as well as in the adaptation to various
      pathological conditions, contributing to the maintenance of bile acid homeostasis
      and functional distribution within the cell. Understanding the mode of binding of
      bile acids with their cytoplasmic transporters is a key issue in providing a
      model for the mechanism of their transfer from the cytoplasm to the nucleus, for
      delivery to nuclear receptors. A number of factors have been shown to modulate
      bile salt selectivity, stoichiometry, and affinity of binding to BABPs, e.g.
      chemistry of the ligand, protein plasticity and, possibly, the formation of
      disulfide bridges. Here, the effects of the presence of a naturally occurring
      disulfide bridge on liver BABP ligand-binding properties and backbone dynamics
      have been investigated by NMR. Interestingly, the disulfide bridge does not
      modify the protein-binding stoichiometry, but has a key role in modulating
      recognition at both sites, inducing site selectivity for glycocholic and
      glycochenodeoxycholic acid. Protein conformational changes following the
      introduction of a disulfide bridge are small and located around the inner binding
      site, whereas significant changes in backbone motions are observed for several
      residues distributed over the entire protein, both in the apo form and in the
      holo form. Site selectivity appears, therefore, to be dependent on protein
      mobility rather than being governed by steric factors. The detected properties
      further establish a parallelism with the behaviour of human ileal BABP,
      substantiating the proposal that BABPs have parallel functions in hepatocytes and
      enterocytes.

PMID- 19754880
TI  - Functional characterization of an orphan cupin protein from Burkholderia
      xenovorans reveals a mononuclear nonheme Fe2+-dependent oxygenase that cleaves
      beta-diketones.
AB  - Cupins constitute a large and widespread superfamily of beta-barrel proteins in
      which a mononuclear metal site is both a conserved feature of the structure and a
      source of functional diversity. Metal-binding residues are contributed from two
      core motifs that provide the signature for the superfamily. On the basis of
      conservation of this two-motif structure, we have identified an ORF in the genome
      of Burkholderia xenovorans that encodes a novel cupin protein (Bxe_A2876) of
      unknown function. Recombinant Bxe_A2876, as isolated from Escherichia coli cell
      extract, was a homotetramer in solution, and showed mixed fractional occupancy of
      its 16.1 kDa subunit with metal ligands (0.06 copper; 0.11 iron; 0.17 zinc). Our
      quest for possible catalytic functions of Bxe_A2876 focused on Cu2+ and Fe2+
      oxygenase activities known from related cupin enzymes. Fe2+ elicited enzymatic
      catalysis of O2-dependent conversion of various beta-diketone substrates via a
      nucleophilic mechanism of carbon-carbon bond cleavage. Data from X-ray absorption
      spectroscopy (XAS) support a five-coordinate or six-coordinate Fe2+ center where
      the metal is bound by three imidazole nitrogen atoms at 1.98 A. Results of
      structure modeling studies suggest that His60, His62 and His102 are the
      coordinating residues. In the 'best-fit' model, one or two oxygens from water and
      a carboxylate oxygen (presumably from Glu96) are further ligands of Fe2+ at
      estimated distances of 2.04 A and 2.08 A, respectively. The three-histidine Fe2+
      site of Bxe_A2876 is compared to the mononuclear nonheme Fe2+ centers of the
      structurally related cysteine dioxygenase and acireductone dioxygenase, which
      also use a facial triad of histidines for binding of their metal cofactor but
      promote entirely different substrate transformations.

PMID- 19754881
TI  - The thioflavin T fluorescence assay for amyloid fibril detection can be biased by
      the presence of exogenous compounds.
AB  - Thioflavin T (ThT) dye fluorescence is used regularly to quantify the formation
      and inhibition of amyloid fibrils in the presence of anti-amyloidogenic compounds
      such as polyphenols. However, in this study, it was shown, using three
      polyphenolics (curcumin, quercetin and resveratrol), that ThT fluorescence should
      be used with caution in the presence of such exogenous compounds. The strong
      absorptive and fluorescent properties of quercetin and curcumin were found to
      significantly bias the ThT fluorescence readings in both in situ real-time ThT
      assays and single time-point dilution ThT-type assays. The presence of curcumin
      at concentrations as low as 0.01 and 1 mum was sufficient to interfere with the
      ThT fluorescence associated with fibrillar amyloid-beta(1-42) (0.5 mum) and
      fibrillar reduced and carboxymethylated kappa-casein (50 mum), respectively. The
      ThT fluorescence associated with fibrillar amyloid-beta(1-42) was also biased
      using higher concentrations of resveratrol, a polyphenol that is not
      spectroscopically active at the wavelengths of ThT fluorescence, implying that
      there can be direct interactions between ThT and the exogenous compound and/or
      competitive binding with ThT for the fibrils. Thus, in all cases where ThT is
      used in the presence of an exogenous compound, biases for amyloid-associated ThT
      fluorescence should be tested, regardless of whether the additive is
      spectroscopically active. Simple methods to conduct these tests were described.
      The Congo red spectral shift assay is demonstrated as a more viable
      spectrophotometric alternative to ThT, but allied methods, such as transmission
      electron microscopy, should also be used to assess fibril formation independently
      of dye-based assays. Structured digital abstract: * MINT-7259867: RCMkappa-CN
      (uniprotkb:P02668) and RCMkappa-CN (uniprotkb:P02668) bind (MI:0407) by electron
      microscopy (MI:0040) * MINT-7258930: RCMkappa-CN (uniprotkb:P02668) and RCMkappa
      CN (uniprotkb:P02668) bind (MI:0407) by fluorescence technologies (MI:0051) *
      MINT-7259878: Amyloid beta (uniprotkb:P05067) and Amyloid beta (uniprotkb:P05067)
      bind (MI:0407) by fluorescence technologies (MI:0051).

PMID- 19754882
TI  - The Pseudomonas aeruginosa nirE gene encodes the S-adenosyl-L-methionine
      dependent uroporphyrinogen III methyltransferase required for heme d(1)
      biosynthesis.
AB  - Biosynthesis of heme d(1), the essential prosthetic group of the dissimilatory
      nitrite reductase cytochrome cd(1), requires the methylation of the tetrapyrrole
      precursor uroporphyrinogen III at positions C-2 and C-7. We produced Pseudomonas
      aeruginosa NirE, a putative S-adenosyl-L-methionine (SAM)-dependent
      uroporphyrinogen III methyltransferase, as a recombinant protein in Escherichia
      coli and purified it to apparent homogeneity by metal chelate and gel filtration
      chromatography. Analytical gel filtration of purified NirE indicated that the
      recombinant protein is a homodimer. NirE was shown to be a SAM-dependent
      uroporphyrinogen III methyltransferase that catalyzes the conversion of
      uroporphyrinogen III into precorrin-2 in vivo and in vitro. A specific activity
      of 316.8 nmol of precorrin-2 h(-1) x mg(-1) of NirE was found for the conversion
      of uroporphyrinogen III to precorrin-2. At high enzyme concentrations NirE
      catalyzed an overmethylation of uroporphyrinogen III, resulting in the formation
      of trimethylpyrrocorphin. Substrate inhibition was observed at uroporphyrinogen
      III concentrations above 17 microM. The protein did bind SAM, although not with
      the same avidity as reported for other SAM-dependent uroporphyrinogen III
      methyltransferases involved in siroheme and cobalamin biosynthesis. A P.
      aeruginosa nirE transposon mutant was not complemented by native cobA encoding
      the SAM-dependent uroporphyrinogen III methyltransferase involved in cobalamin
      formation. However, bacterial growth of the nirE mutant was observed when cobA
      was constitutively expressed by a complementing plasmid, underscoring the special
      requirement of NirE for heme d(1) biosynthesis.

PMID- 19754884
TI  - Species-specific responses to atmospheric carbon dioxide and tropospheric ozone
      mediate changes in soil carbon.
AB  - We repeatedly sampled the surface mineral soil (0-20 cm depth) in three northern
      temperate forest communities over an 11-year experimental fumigation to
      understand the effects of elevated carbon dioxide (CO(2)) and/or elevated phyto
      toxic ozone (O(3)) on soil carbon (C). After 11 years, there was no significant
      main effect of CO(2) or O(3) on soil C. However, within the community containing
      only aspen (Populus tremuloides Michx.), elevated CO(2) caused a significant
      decrease in soil C content. Together with the observations of increased litter
      inputs, this result strongly suggests accelerated decomposition under elevated
      CO(2.) In addition, an initial reduction in the formation of new (fumigation
      derived) soil C by O(3) under elevated CO(2) proved to be only a temporary
      effect, mirroring trends in fine root biomass. Our results contradict predictions
      of increased soil C under elevated CO(2) and decreased soil C under elevated O(3)
      and should be considered in models simulating the effects of Earth's altered
      atmosphere.

PMID- 19754885
TI  - The ecological stoichiometry of toxins produced by harmful cyanobacteria: an
      experimental test of the carbon-nutrient balance hypothesis.
AB  - The elemental composition of primary producers reflects the availability of
      light, carbon and nutrients in their environment. According to the carbon
      nutrient balance hypothesis, this has implications for the production of
      secondary metabolites. To test this hypothesis, we investigated a family of
      toxins, known as microcystins, produced by harmful cyanobacteria. The strain
      Microcystis aeruginosa HUB 5-2-4, which produces several microcystin variants of
      different N:C stoichiometry, was cultured in chemostats supplied with various
      combinations of nitrate and CO(2). Excess supply of both nitrogen and carbon
      yielded high cellular N:C ratios accompanied by high cellular contents of total
      microcystin and the nitrogen-rich variant microcystin-RR. Comparable patterns
      were found in Microcystis-dominated lakes, where the relative microcystin-RR
      content increased with the seston N:C ratio. In total, our results are largely
      consistent with the carbon-nutrient balance hypothesis, and warn that a
      combination of rising CO(2) and nitrogen enrichment will affect the microcystin
      composition of harmful cyanobacteria.

PMID- 19754886
TI  - Calcium signaling in cells of the immune and hematopoietic systems.

PMID- 19754887
TI  - Capacitative calcium entry: from concept to molecules.
AB  - Rapid to moderately rapid changes in intracellular Ca2+ concentration, or Ca2+
      signals, control a variety of critical cellular functions in the immune system.
      These signals are comprised of Ca2+ release from intracellular stores coordinated
      with Ca2+ influx across the plasma membrane. The most common mechanisms by which
      these two modes of signaling occur is through inositol 1,4,5-trisphosphate (IP3)
      induced release of Ca2+ from the endoplasmic reticulum (ER) and store-operated
      Ca2+ entry across the plasma membrane. The latter process was postulated over 20
      years ago, and in just the past few years, the key molecular players have been
      discovered: STIM proteins serve as sensors of Ca2+ within the ER which
      communicate with and activate plasma membrane store-operated channels composed of
      Orai subunits. The process of store-operated Ca2+ entry provides support for
      oscillating Ca2+ signals from the ER and also provides direct activator Ca2+ that
      signals to a variety of downstream effectors.

PMID- 19754888
TI  - IP3 receptors: some lessons from DT40 cells.
AB  - Inositol-1,4,5-trisphosphate receptors (IP3Rs) are intracellular Ca2+ channels
      that are regulated by IP3 and Ca2+ and are modulated by many additional signals.
      These properties allow them to initiate and, via Ca2+-induced Ca2+ release,
      regeneratively propagate Ca2+ signals evoked by receptors that stimulate
      formation of IP3. The ubiquitous expression of IP3R highlights their importance,
      but it also presents problems when attempting to resolve the behavior of defined
      IP3R. DT40 cells are a pre-B-lymphocyte cell line in which high rates of
      homologous recombination afford unrivalled opportunities to disrupt endogenous
      genes. DT40-knockout cells with both alleles of each of the three IP3R genes
      disrupted provide the only null-background for analysis of homogenous recombinant
      IP3R. We review the properties of DT40 cells and consider three areas where they
      have contributed to understanding IP3R behavior. Patch-clamp recording from the
      nuclear envelope and Ca2+ release from intracellular stores loaded with a low
      affinity Ca2+ indicator address the mechanisms leading to activation of IP(3)R.
      We show that IP3 causes intracellular IP3R to cluster and re-tune their responses
      to IP3 and Ca2+, better equipping them to mediate regenerative Ca2+ signals.
      Finally, we show that DT40 cells reliably count very few IP3R into the plasma
      membrane, where they mediate about half the Ca2+ entry evoked by the B-cell
      antigen receptor.

PMID- 19754889
TI  - CRAC channels and Ca2+ signaling in mast cells.
AB  - Mast cells are integral members of the immune system. Upon activation by a rise
      in cytoplasmic Ca2+, they release a battery of paracrine signals, chemokines, and
      cytokines, which help sculpt the subsequent immune response. Ca2+ entry through
      store-operated Ca2+ release-activated Ca2+ (CRAC) channels in the plasma membrane
      is central for driving most of these responses. The molecular basis of the CRAC
      channel has been identified, with Orai1 forming the channel pore. Recent work has
      revealed that a range of mast cell responses are activated by spatially
      restricted Ca2+ signals just below the plasma membrane. These Ca2+ microdomains
      can activate cytosolic enzymes, leading to the generation of intracellular
      messengers as well as proinflammatory molecules like LTC4. In this review, we
      describe key features of CRAC channels in mast cells, how they generate local
      Ca2+ signals, and how the cell can decode these restricted signals to generate a
      raft of responses.

PMID- 19754892
TI  - Mechanistic view on domains mediating STIM1-Orai coupling.
AB  - Calcium (Ca2+) entry into non-excitable cells is mainly carried by store-operated
      channels, which serve essential functions ranging from regulation of
      transcription to cell growth. The best-characterized store-operated current,
      initially discovered in T lymphocytes and mast cells, is the Ca2+ release
      activated Ca2+ (CRAC) current. The search for the molecular components of the
      CRAC channel has recently identified stromal interaction molecule 1 (STIM1) as
      the Ca2+ sensor in the endoplasmic reticulum (ER) and Orai1 as the CRAC channel
      pore. ER store depletion results in formation of STIM1 puncta that trigger Ca2+
      influx via Orai1 channels. This review covers the role of domains within STIM1
      and Orai and enlightens their function in the STIM1/Orai coupling process.
      Moreover, a molecular interpretation focuses on interactions between cytosolic
      portions of STIM1 and Orai together with a mechanistic view on the loss of
      function of the SCID (severe combined immunodeficiency)-linked Orai1 R91W mutant
      channel. The architecture of the selectivity filter of Orai channels is finally
      elucidated based on permeation properties of Orai pore mutants.

PMID- 19754891
TI  - The molecular physiology of CRAC channels.
AB  - The Ca2+release-activated Ca2+ (CRAC) channel is a highly Ca2+-selective store
      operated channel expressed in T cells, mast cells, and various other tissues.
      CRAC channels regulate critical cellular processes such as gene expression,
      motility, and the secretion of inflammatory mediators. The identification of
      Orai1, a key subunit of the CRAC channel pore, and STIM1, the endoplasmic
      reticulum (ER) Ca2+ sensor, have provided the tools to illuminate the mechanisms
      of regulation and the pore properties of CRAC channels. Recent evidence indicates
      that the activation of CRAC channels by store depletion involves a coordinated
      series of steps, which include the redistributions of STIM1 and Orai1, direct
      physical interactions between these proteins, and conformational changes in
      Orai1, culminating in channel activation. Additional studies have revealed that
      the high Ca2+ selectivity of CRAC channels arises from the presence of an
      intrapore Ca2+ binding site, the properties of which are finely honed to occlude
      the permeation of the much more prevalent Na+. Structure-function studies have
      led to the identification of the potential pore-binding sites for Ca2+, providing
      a firm framework for understanding the mechanisms of selectivity and gating of
      the CRAC channel. This review summarizes recent progress in understanding the
      mechanisms of CRAC channel activation, pore properties, and modulation.

PMID- 19754890
TI  - The functional network of ion channels in T lymphocytes.
AB  - For more than 25 years, it has been widely appreciated that Ca2+ influx is
      essential to trigger T-lymphocyte activation. Patch clamp analysis, molecular
      identification, and functional studies using blockers and genetic manipulation
      have shown that a unique contingent of ion channels orchestrates the initiation,
      intensity, and duration of the Ca2+ signal. Five distinct types of ion channels-
      Kv1.3, KCa3.1, Orai1+ stromal interacting molecule 1 (STIM1) [Ca2+-release
      activating Ca2+ (CRAC) channel], TRPM7, and Cl(swell)--comprise a network that
      performs functions vital for ongoing cellular homeostasis and for T-cell
      activation, offering potential targets for immunomodulation. Most recently, the
      roles of STIM1 and Orai1 have been revealed in triggering and forming the CRAC
      channel following T-cell receptor engagement. Kv1.3, KCa3.1, STIM1, and Orai1
      have been found to cluster at the immunological synapse following contact with an
      antigen-presenting cell; we discuss how channels at the synapse might function to
      modulate local signaling. Immuno-imaging approaches are beginning to shed light
      on ion channel function in vivo. Importantly, the expression pattern of Ca2+ and
      K+ channels and hence the functional network can adapt depending upon the state
      of differentiation and activation, and this allows for different stages of an
      immune response to be targeted specifically.

PMID- 19754893
TI  - Structurally delineating stromal interaction molecules as the endoplasmic
      reticulum calcium sensors and regulators of calcium release-activated calcium
      entry.
AB  - The endoplasmic reticulum (ER) lumen stores a crucial source of calcium (Ca2+)
      maintained orders of magnitude higher than the cytosol for the activation of a
      plethora of cellular responses transmitted in health and disease by a mutually
      efficient and communicative exchange of Ca2+ between compartments. A coordination
      of the Ca2+ signal is evident in the development of Ca2+ release-activated Ca2+
      (CRAC) entry, vital to lymphocyte activation and replenishing of the ER Ca2+
      stores, where modest decreases in ER luminal Ca2+ induce sustained increases in
      cytosolic Ca2+ sourced from steadfast extracellular Ca2+ supplies. While protein
      sensors that transduce Ca2+ signals in the cytosol such as calmodulin are
      succinctly understood, comparative data on the ER luminal Ca2+ sensors is only
      recently coming to light with the discovery that stromal interaction molecules
      (STIMs) sense variations in ER stored Ca2+ levels in the functional regulation of
      plasma membrane Orai proteins, the major component of CRAC channel pores. Drawing
      from data on the role of STIMs in the modulation of CRAC entry, this review
      illustrates the structural features that delimit the functional characteristics
      of ER Ca2+ sensors relative to well known cytoplasmic Ca2+ sensors.

PMID- 19754894
TI  - The immunological synapse controls local and global calcium signals in T
      lymphocytes.
AB  - Cell polarization is a key feature of T-cell function. The immunological synapse
      (IS) between T cells and antigen-presenting cells is a beautiful example of how
      polarization of cells is used to guide cell function. Receptors, signal
      transducers, the cytoskeleton, and organelles are enriched at or depleted from
      the IS after its formation, and in many cases these re-localizations have already
      been linked with certain T-cell functions. One key step for T-cell activation is
      a rise in the cytoplasmic calcium concentration. Whereas it is undisputed that
      the IS initiates and controls calcium signals in T cells, very little is known
      about the role of T-cell polarization for calcium signals and calcium-dependent
      signal transduction. We briefly summarize the basic commonly agreed principles of
      IS-dependent calcium signal generation but then focus on the less well understood
      influence of polarization on calcium signals. The discussion of the role of
      polarization for calcium signals leads to a model how the IS controls local and
      global calcium signals and calcium-dependent T-cell functions. We develop a
      theoretical formalism based on existing spatiotemporal calcium dynamic
      simulations to better understand the model in the future and allow further
      predictions which can be tested by fast, high resolution live-cell microscopy.

PMID- 19754896
TI  - Calcium influx and signaling in cytotoxic T-lymphocyte lytic granule exocytosis.
AB  - Cytotoxic T lymphocytes (CTLs) kill targets by releasing cytotoxic agents from
      lytic granules. Killing is a multi-step process. The CTL adheres to a target,
      allowing its T-cell receptors to recognize antigen. This triggers a signal
      transduction cascade that leads to the polarization of the microtubule
      cytoskeleton and granules towards the target, followed by exocytosis that occurs
      specifically at the site of contact. As with cytokine production by helper T
      cells (Th cells), target cell killing is absolutely dependent on Ca2+ influx,
      which is involved in regulating both reorientation and release. Current evidence
      suggests that Ca2+ influx in CTLs, as in Th cells, occurs via depletion-activated
      channels. The molecules that couple increases in Ca2+ to reorientation are
      unknown. The Ca2+/calmodulin-dependent phosphatase calcineurin, which plays a
      critical role in cytokine production by Th cells, is also involved in lytic
      granule exocytosis, although the relevant substrates remain to be identified and
      calcineurin activation is only one Ca2+-dependent step involved. There are thus
      striking similarities and important differences between Ca2+ signals in Th cells
      and CTLs, illustrating how cells can use similar signal transduction pathways to
      generate different functional outcomes.

PMID- 19754895
TI  - Formation of STIM and Orai complexes: puncta and distal caps.
AB  - In the last few years, great progress has been made in understanding how stromal
      interacting molecule 1 (STIM1), a protein containing a calcium sensor that is
      located in the endoplasmic reticulum, and Orai1, a protein that forms a calcium
      channel in the plasma membrane, interact and give rise to store-operated calcium
      entry. Pharmacological depletion of calcium stores leads to the formation of
      clusters containing STIM and Orai that appear to be sites for calcium influx.
      Similar puncta are also produced in response to physiological stimuli in immune
      cells. In T cells engaged with antigen-presenting cells, clusters containing STIM
      and Orai accumulate at the immunological synapse. We recently discovered that in
      activated T cells, STIM1 and Orai1 also accumulate in cap-like structures
      opposite the immune synapse at the distal pole of the cell. Both caps and puncta
      are long-lived stable structures containing STIM1 and Orai1 in close proximity.
      The function of puncta as sites of calcium influx is clear. We speculate that the
      caps may provide a secondary site of calcium entry. Alternatively, they may serve
      as a source of preformed channel complexes that move to new immune synapses as T
      cells repeatedly engage antigen-presenting cells.

PMID- 19754897
TI  - Physiological function and molecular basis of STIM1-mediated calcium entry in
      immune cells.
AB  - Calcium signals in immune cells regulate a variety of physiological responses
      such as cell activation, differentiation, gene transcription, and effector
      functions. Surface receptor stimulation induces an increase in the concentration
      of cytosolic calcium ions (Ca2+), which are derived mainly from two sources,
      intracellular endoplasmic reticulum (ER) Ca2+ stores and the extracellular space.
      The major cascade for Ca2+ entry in immune cells is through store-operated Ca2+
      entry (SOCE) and Ca2+ release-activated Ca2+ (CRAC) channels. Activation of SOCE
      is triggered by depletion of intracellular ER Ca2+ stores, but the molecular
      mechanism was a long-standing issue. With the recent molecular identification of
      the ER Ca2+ sensor [stromal interacting molecule-1 (STIM1)] and a pore-forming
      subunit of the CRAC channel (Orai1), our understanding of the SOCE activation
      pathway has increased dramatically. These advances have now made it possible to
      shed some light on important questions: what is the physiological significance of
      SOCE, and what is its molecular basis? This review focuses on the recent progress
      in the field and the exciting opportunities for understanding how SOCE influences
      diverse immune functions.

PMID- 19754898
TI  - ORAI1 and STIM1 deficiency in human and mice: roles of store-operated Ca2+ entry
      in the immune system and beyond.
AB  - Store-operated Ca2+ entry (SOCE) is a mechanism used by many cells types
      including lymphocytes and other immune cells to increase intracellular Ca2+
      concentrations to initiate signal transduction. Activation of immunoreceptors
      such as the T-cell receptor, B-cell receptor, or Fc receptors results in the
      release of Ca2+ ions from endoplasmic reticulum (ER) Ca2+ stores and subsequent
      activation of plasma membrane Ca2+ channels such as the well-characterized Ca2+
      release-activated Ca2+ (CRAC) channel. Two genes have been identified that are
      essential for SOCE: ORAI1 as the pore-forming subunit of the CRAC channel in the
      plasma membrane and stromal interaction molecule-1 (STIM1) sensing the ER Ca2+
      concentration and activating ORAI1-CRAC channels. Intense efforts in the past
      several years have focused on understanding the molecular mechanism of SOCE and
      the role it plays for cell functions in vitro and in vivo. A number of transgenic
      mouse models have been generated to investigate the role of ORAI1 and STIM1 in
      immunity. In addition, mutations in ORAI1 and STIM1 identified in immunodeficient
      patients provide valuable insight into the role of both genes and SOCE. This
      review focuses on the role of ORAI1 and STIM1 in vivo, discussing the phenotypes
      of ORAI1- and STIM1-deficient human patients and mice.

PMID- 19754899
TI  - Calcium signaling in the development and function of T-lineage cells.
AB  - Ca2+ signals are essential for diverse cellular functions including
      differentiation, effector function, and gene transcription in the immune system.
      In lymphocytes, sustained Ca2+ entry is necessary for complete and long-lasting
      activation of calcineurin/nuclear factor of activated T cells (NFAT) pathways.
      Engagement of immunoreceptors, such as the T-cell antigen receptor, induces store
      operated Ca2+ entry (SOCE) through plasma membrane Ca2+ channels. In lymphocytes,
      mast cells, and other immune cell types, SOCE through highly Ca2+-selective Ca2+
      release-activated Ca2+ (CRAC) channels constitute the major pathway of
      intracellular Ca2+ increase. A recent breakthrough in our understanding of CRAC
      channel function is the identification of STIM and ORAI, two essential regulators
      of CRAC channel function. This discovery allows us to directly address the
      physiological role of Ca2+ entry in lymphocytes. A growing number of studies have
      emphasized that Ca2+/calcineurin/NFAT pathway is crucial for both development and
      function of all T-cell lineage cells, such as conventional alphabeta+ TCR T
      cells, Foxp3+ regulatory T cells, and invariant natural killer T cells. This
      review focuses on the role of the signaling pathways upstream and downstream of
      Ca2+ influx in the development and function in T-cell lineages.

PMID- 19754900
TI  - Regulation of T-cell tolerance by calcium/NFAT signaling.
AB  - Cells that escape negative selection in the thymus must be inactivated or
      eliminated in the periphery through a series of mechanisms that include the
      induction of anergy, dominant suppression by regulatory T cells, and peripheral
      deletion of self-reactive T cells. Calcium signaling plays a central role in the
      induction of anergy in T cells, which become functionally inactivated and
      incapable of proliferating and expressing cytokines following antigen re
      encounter. Suboptimal stimulation of T cells results in the activation of a
      calcium/calcineurin/nuclear factor of activated T cells-dependent cell-intrinsic
      program of self-inactivation. The proteins encoded by those genes are required to
      impose a state of functional unresponsiveness through different mechanisms that
      include downregulation of T-cell receptor signaling and inhibition of cytokine
      transcription.

PMID- 19754901
TI  - Ca2+-NFATc1 signaling is an essential axis of osteoclast differentiation.
AB  - Osteoclasts are unique, multinucleated giant cells that decalcify and degrade the
      bone matrix. They originate from hematopoietic cells and their differentiation is
      dependent on a tumor necrosis factor (TNF) family cytokine, receptor activator of
      nuclear factor-kappaB (NF-kappaB) ligand (RANKL), as well as macrophage-colony
      stimulating factor (M-CSF). Recent studies have unveiled the precise molecular
      mechanism underlying osteoclastogenesis. In particular, the discovery of nuclear
      factor of activated T cells c1 (NFATc1), the master regulator of
      osteoclastogenesis, has proven to be a breakthrough in this field. NFATc1 is
      activated by Ca2+ signaling induced by the activation of the immunoglobulin-like
      receptor signaling associated with immunoreceptor tyrosine-based activation motif
      (ITAM)-harboring adapters. The long-lasting Ca2+ oscillation, which is evident
      during osteoclastogenesis, may ensure the robust induction of NFATc1 through an
      autoamplification mechanism. Thus, intracellular Ca2+ is a critical attribute of
      osteoclastogenic signaling. In addition, osteoclasts are exposed to a very high
      extracellular Ca2+ concentration ([Ca2+]o) in the bone microenvironment and
      respond to the change in [Ca2+]o by increasing the intracellular Ca2+, which
      regulates diverse cellular functions. Investigation of the molecular mechanisms
      underlying the regulation of intracellular Ca2+ dynamics may open up new
      directions for therapeutic strategies in bone disease.

PMID- 19754902
TI  - Roles of Ca(v) channels and AHNAK1 in T cells: the beauty and the beast.
AB  - T lymphocytes require Ca2+ entry though the plasma membrane for their activation
      and function. Recently, several routes for Ca2+ entry through the T-cell plasma
      membrane after activation have been described. These include calcium release
      activated channels (CRAC), transient receptor potential (TRP) channels, and
      inositol-1,4,5-trisphosphate receptors (IP3Rs). Herein we review the emergence of
      a fourth new route for Ca2+ entry, composed of Ca(v) channels (also known as L
      type voltage-gated calcium channels) and the scaffold protein AHNAK1
      (AHNAK/desmoyokin). Both helper (CD4+) and killer (CD8+) T cells express high
      levels of Ca(v)1 alpha1 subunits (alpha1S, alpha1C, alpha1D, and alpha1F) and
      AHNAK1 after their differentiation and require these molecules for Ca2+ entry
      during an immune response. In this article, we describe the observations and open
      questions that ultimately suggest the involvement of multiple consecutive routes
      for Ca2+ entry into lymphocytes, one of which may be mediated by Ca(v) channels
      and AHNAK1.

PMID- 19754904
TI  - Dendritic cell altered states: what role for calcium?
AB  - Ca2+-driven responses in dendritic cells (DCs) are less well characterized than
      in lymphocytes. When DCs undergo a sequence of activation/maturation events,
      typically beginning with exposure to pathogens in the periphery, Ca2+ entry into
      the cytosol from stores in the endoplasmic reticulum or from outside the cell can
      occur at various steps and participate in intracellular signaling. However, not
      all cellular processes identified in these cells are Ca2+ dependent. While
      immigration of precursor DCs into the peripheral tissues as well as emigration to
      secondary lymphoid sites following microbial challenge depend on processes that
      involve Ca2+, other processes such as DC maturation in response to Toll-like
      receptor agonist stimulation appear not to. Certain microbial stimuli and host
      derived chemokines induce Ca2+ entry that is important for the induced responses.
      In this article, we review the current state of our understanding of the role of
      Ca2+ in DC biology and argue that homeostatic control of Ca2+ levels in these
      cells is critical for maintaining their proper function. We also consider
      evidence for intercellular transmission of Ca2+ signals between DCs that are
      physically linked by thin membranous extensions termed tunneling nanotubules.

PMID- 19754903
TI  - B-lymphocyte calcium influx.
AB  - Dynamic changes in cytoplasmic calcium concentration dictate the immunological
      fate and functions of lymphocytes. During the past few years, important details
      have been revealed about the mechanism of store-operated calcium entry in
      lymphocytes, including the molecular identity of calcium release-activated
      calcium (CRAC) channels and the endoplasmic reticulum (ER) calcium sensor (STIM1)
      responsible for CRAC channel activation following calcium depletion of stores.
      However, details of the potential fine regulation of CRAC channel activation that
      may be imposed on lymphocytes following physiologic stimulation within an
      inflammatory environment have not been fully addressed. In this review, we
      discuss several underexplored aspects of store-operated (CRAC-mediated) and store
      independent calcium signaling in B lymphocytes. First, we discuss results
      suggesting that coupling between stores and CRAC channels may be regulated,
      allowing for fine tuning of CRAC channel activation following depletion of ER
      stores. Second, we discuss mechanisms that sustain the duration of calcium entry
      via CRAC channels. Finally, we discuss distinct calcium permeant non-selective
      cation channels (NSCCs) that are activated by innate stimuli in B cells, the
      potential means by which these innate calcium signaling pathways and CRAC
      channels crossregulate one another, and the mechanistic basis and physiologic
      consequences of innate calcium signaling.

PMID- 19754905
TI  - Allometric scaling of clearance in dogs.
AB  - Most drugs indicated for use in dogs are labeled for administration on a mg/kg
      basis. Such dosing recommendations are grounded on an assumption that total body
      clearance (Cl) scales in a manner directly proportional to body weight (i.e. that
      it scales with an allometric exponent of 1). Despite the critical nature of this
      assumption (the range of normal canine body weights can go from as small as 2 lbs
      to almost 200 lbs), the validity of this assumption has not been rigorously
      challenged. Therefore, this manuscript provides an initial assessment of the
      potential ramifications of this assumption. This objective was accomplished
      through the following three sets of analysis: (i) examining the observed vs.
      predicted Cl values across 10 drugs based upon interspecies scaling; (ii)
      estimating the difference in area under the concentration vs. time curve values
      if Cl scaled directly in proportion to body weight vs. in a manner consistent
      with the allometric exponent estimated in the first data analysis; and (iii)
      exploring the impact of breed differences in drug metabolism that may further
      confound the problem of exposure assessment. Based upon this assessment, we
      conclude that if Cl does not scale directly in proportion to body weight, the
      actual drug exposure in large or small dogs could differ markedly from those
      concentrations estimated on the basis of studies conducted in beagle-sized dogs.

PMID- 19754906
TI  - Biliary excretion of technetium-99m-sestamibi in wild-type dogs and in dogs with
      intrinsic (ABCB1-1Delta mutation) and extrinsic (ketoconazole treated) P
      glycoprotein deficiency.
AB  - P-glycoprotein (P-gp), the product of ABCB1 gene, is thought to play a role in
      the biliary excretion of a variety of drugs, but specific studies in dogs have
      not been performed. Because a number of endogenous (ABCB1 polymorphisms) and
      exogenous (pharmacological P-gp inhibition) factors can interfere with normal P
      gp function, a better understanding of P-gp's role in biliary drug excretion is
      crucial in preventing adverse drug reactions and drug-drug interactions in dogs.
      The objectives of this study were to compare biliary excretion of technetium-99m
      sestamibi ((99m)Tc-MIBI), a radio-labelled P-gp substrate, in wild-type dogs
      (ABCB1 wild/wild), and dogs with intrinsic and extrinsic deficiencies in P-gp
      function. Dogs with intrinsic P-gp deficiency included ABCB1 mut/mut dogs, and
      dogs with presumed intermediate P-gp phenotype (ABCB1 mut/wild). Dogs with
      extrinsic P-gp deficiency were considered to be ABCB1 wild/wild dogs treated with
      the P-gp inhibitor ketoconazole (5 mg/kg PO q12h x 9 doses). Results from this
      study indicate that ABCB1 mut/mut dogs have significantly decreased biliary
      excretion of (99m)Tc-MIBI compared with ABCB1 wild/wild dogs. Treatment with
      ketoconazole significantly decreased biliary excretion of (99m)Tc-MIBI in ABCB1
      wild/wild dogs. P-gp appears to play an important role in the biliary excretion
      of (99m)Tc-MIBI in dogs. It is likely that concurrent administration of a P-gp
      inhibitor such as ketoconazole will decrease P-gp-mediated biliary excretion of
      other substrate drugs as well.

PMID- 19754907
TI  - Cultured mammary epithelial monolayers (BME-UV) express functional organic anion
      and cation transporters.
AB  - There is ongoing concern about the potential adverse effects of xenobiotic
      residues in cows' milk to the human consumer. Although drugs that are
      intentionally administered to lactating dairy cattle are rigorously regulated to
      prevent harmful residues, there are numerous other potential sources of exposure
      that are not as easily controlled. For example, cattle may be exposed to
      mycotoxins, pesticides and/or persistent organic pollutants through feed, water
      and inhalation of polluted air. Accurate estimates of the rate and extent of
      excretion of these compounds into milk is important to assess the risk of
      exposure through cows' milk. In the present study, the expression of carrier
      mediated transport processes in cultured monolayers of an immortalized bovine
      mammary epithelial cell line (BME-UV) was determined using a flow-through
      diffusion cell system, selective substrates and inhibitors of organic cation
      transporters (OCT) and organic anion transporters (OAT). The basal-to-apical (BL
      to-Ap) flux of tetraethylammonium and estrone sulfate significantly exceeded
      their flux in the opposite direction. The addition of selective inhibitors to the
      donor compartment significantly decreased the BL-to-Ap flux of either selective
      substrate. These results suggest that both OCT and OAT are functionally expressed
      by BME-UV cells.

PMID- 19754908
TI  - In vitro kinetics of hepatic albendazole sulfoxidation in channel catfish
      (Ictalurus punctatus), tilapia (Oreochromis sp.), rainbow trout (Oncorhynchus
      mykiss) and induction of EROD activity in ABZ-dosed channel catfish.
AB  - Liver microsomes from market-size (n = 6) rainbow trout, channel catfish and
      tilapia were used to investigate in vitro biotransformation kinetics of
      albendazole (ABZ). ABZ was transformed to a single metabolite, ABZ sulfoxide (ABZ
      SO). Catfish displayed the highest maximal velocity (V(max) = 264.0 +/- 58.6
      pmols ABZ-SO/min/mg protein) followed by tilapia (112.3 +/- 8.2) and rainbow
      trout (73.3 +/- 10.3). V(max) in catfish was significantly different (P < 0.05)
      from the other two species. Michaelis-Menten constant (K(m)) values (microm)
      varied significantly among the species: rainbow trout (3.9 +/- 0.5), tilapia (9.2
      +/- 1.7) and catfish (22.0 +/- 3.2). However, V(max)/K(m) ratios showed no
      difference among the three species, making them equally efficient performing this
      phase I biotransformation reaction. In a second series of experiments, channel
      catfish (n = 6 per treatment) were dosed in vivo with gel-food containing ABZ (10
      mg/kg, p.o.). Fish were killed at 24, 48, 72 and 120 h after dosage. Control fish
      were fed ABZ-free feed. Induction of ethoxyresorufin-o-deethylase activity was
      significant (P < 0.05) in all ABZ-dosed treatments as compared with controls.

PMID- 19754909
TI  - Pharmacokinetic and pharmacodynamic evaluation of propofol administered to cats
      in a novel, aqueous, nano-droplet formulation or as an oil-in-water
      macroemulsion.
AB  - This study evaluated pharmacokinetic and pharmacologic properties of a novel, non
      lipid microemulsion, 1% w/v formulation of propofol to a conventional
      macroemulsion formulation of propofol (Rapinovet) in cats. The study utilized a
      two-period crossover design with two treatments and 10 female, intact, purpose
      bred domestic shorthair cats. Cats were fitted with telemetry transmitters for
      direct measurement of arterial blood pressure, pulse rate, electrocardiogram
      (ECG, lead II), and body temperature. At least 7 days separated treatments.
      Orotracheal intubation was the clinical endpoint utilized to evaluate adequate
      depth of anesthesia. Blood samples were drawn from jugular vascular access ports
      before propofol treatment; 3, 5, 15, 25, 35, 45, and 60 min and then 2, 3, 6, 8,
      12, 18, and 24 h after administration of propofol into a cephalic vein. Whole
      blood samples were assayed for propofol concentrations using a gas
      chromatography/mass spectrometry method validated for feline blood at a limit of
      quantification of 5 ng/mL. Pulse rate, ECG, heart rhythm, respiratory rate,
      systolic, diastolic and mean arterial blood pressures, SpO2, and body temperature
      were monitored continuously during each anesthetic episode. Time to lateral
      recumbency, orotracheal intubation, and extubation, time to sternal recumbency
      during recovery, times to adverse events, and doses of propofol required for
      induction to anesthesia were documented. Cats required 6.96 +/- 0.90 mg
      propofol/kg from the novel microemulsion formulation of propofol and 7.07 +/-
      1.55 mg propofol/kg from Rapinovet to achieve anesthesia adequate to allow
      orotracheal intubation (P > 0.05). Areas under the dose-normalized propofol
      concentration by time curves (AUC(0-LOQ)) and maximum propofol concentrations
      (C(max)) were equal for the novel microemulsion formulation of propofol and
      Rapinovet (P > 0.05). Effects of anesthesia induction doses on cardiorespiratory
      values were comparable between treatments, and consistent with known effects of
      propofol anesthesia. Results provide evidence that the novel microemulsion
      formulation of propofol and Rapinovet macroemulsion produced comparable
      pharmacodynamic, physiological, and pharmacokinetic responses in cats. The unique
      composition of the microemulsion formulation, and the presence of an
      antimicrobial preservative minimize the potential for bacterial contamination and
      prolong shelf life.

PMID- 19754910
TI  - Pharmacokinetics of lidocaine in serum and milk of mature Holstein cows.
AB  - The purpose of this study was to evaluate the pharmacokinetics of lidocaine in
      mature Holstein cows following an inverted L and caudal epidural nerve block.
      Plasma and milk concentrations were determined using high-performance liquid
      chromatography assay. Pharmacokinetic parameters were estimated using a
      noncompartmental method. Following administration via inverted L nerve block,
      serum T(max) was 0.521 +/- 0.226 h and serum C(max) was 572 +/- 207 ng/mL. Serum
      AUC was 1348 +/- 335 ng.h/mL. Apparent serum t((1/2)beta) was 4.19 +/- 1.69 h and
      MRT was 5.13 +/- 2.33 h with clearance uncorrected for the extent of absorption
      of 2.75 +/- 0.68 L/kg/h. The last measurable time of lidocaine detection in serum
      was 8.5 +/- 1.4 h with a mean concentration of 51 +/- 30 ng/mL. Milk T(max) was
      detected at 1.75 +/- 0.46 h with C(max) of 300 +/- 139 ng/mL. Milk AUC till the
      last time was 1869 +/- 450 ng.h/mL with the mean AUC milk to AUC serum ratio of
      1.439 +/- 0.374. The last measurable time of lidocaine detection in milk was 32.5
      +/- 16.2 h with a mean concentration of 46 +/- 30 ng/mL. There was no detectable
      lidocaine concentration in any samples following caudal epidural administration.

PMID- 19754911
TI  - Bioavailability, distribution and depletion of monensin in chickens.
AB  - The pharmacokinetics of monensin including apparent volume of distribution, total
      body clearance, systemic bioavailability, partition coefficients and tissue
      residues were determined in chickens. The drug was given by intravenous injection
      in the left wing vein at the dose of 0.46 mg/kg and by intracrop administration
      at the dose of 4 mg/kg according to a destructive sampling. The pharmacokinetic
      variables were compared after noncompartmental, naive averaged, naive pooled and
      nonlinear mixed-effects modelling analyses. Partition coefficients and tissue
      residues were determined after a treatment with feed additives (125 mg/kg of
      feed) of 33 days. The clearance, volume of distribution and bioavailabilty were
      approximately 2.2 L/h/kg, approximately 9 L/kg and approximately 30% respectively
      except with nonlinear mixed effects models that presented values of 1.77 L/h/kg,
      14.05 L/kg and 11.36% respectively. Tissue/plasma partition coefficients were
      estimated to 0.83, 3.39 and 0.51 for liver, fat and thigh muscle respectively.
      Monensin residues after treatment were not detected 6 h after withdrawal except
      for fat where monensin was still quantifiable 12 h after. Pharmacokinetic
      variables seem to be inaccurate when assessed with non linear mixed-effects
      modelling associated to destructive sampling in chickens. Values varied slightly
      with noncompartmental, naive averaged and naive pooled analyses. The absorption,
      elimination and partition parameters will be incorporated into a physiologically
      based pharmacokinetic model and the depletion study will be used to test the
      ability of this model to describe monensin residues in edible tissues under
      different dosage regimens.

PMID- 19754912
TI  - Influence of the injection site on the pharmacokinetics of amoxicillin after
      intramuscular administration of a conventional and a long-acting formulation in
      sheep.
AB  - The pharmacokinetics of amoxicillin (AMX) were investigated in sheep following
      intravenous (i.v.) and intramuscular (i.m) injection, comparing two different
      drug formulations, a conventional and a long-acting AMX-trihydrate suspension.
      For the i.m. application two different injections sites, the neck area and the
      hind limb were used to identify possible differences in the kinetic parameters
      related to the site of injection. A three-compartment open model could best
      describe AMX disposition after i.v. administration. Data analysis after i.m.
      administration of the conventional suspension at both injection sites revealed
      the occurrence of a flip-flop phenomenon, clearly indicating that absorption of
      AMX is the rate-limiting step of its overall disposition. A moderate effect of
      the injection site was observed with a tendency for the neck area to be
      advantageous, mainly in terms of rate rather than extent of absorption. Injection
      of the long-acting formulation led to a focal depot formation, thus yielding
      lower but remarkably prolonged serum AMX levels reflected in the respective
      terminal half-lives. The concentration-time profile of AMX after administration
      of the long-acting formulation was less affected by the injection site, but the
      low serum levels justify its use only in cases in which a high susceptibility of
      the involved bacterial population is confirmed.

PMID- 19754913
TI  - Experimental acute toxicity of xylitol in dogs.
AB  - The Cases of xylitol poisoning in dogs are increasing as a result of ingestion of
      xylitol-containing products. Eighteen adult, clinically normal Pekingese dogs
      were orally dosed with 1 or 4 g/kg xylitol in aqueous solution. Blood samples
      were collected before and after dosing. Plasma insulin concentrations of both
      treated groups rose sharply from 20 min after xylitol dosing, peaking at 40 min.
      Hypoglycemia followed the increase in insulin concentration, with blood glucose
      values started to decrease 30 min after dosing. Other plasma biochemistry changes
      associated with xylitol administration were increased alanine aminotransferase
      and aspartate aminotransferase activities, hypophosphatemia, hypokalemia, and
      hypercalcemia. Plasma sodium and chloride concentrations remained normal. This
      study established a biochemical basis for diagnosis and treatment of xylitol
      poisoning in dogs.

PMID- 19754914
TI  - Isolation of two cytochrome P450 forms, CYP2A19 and CYP1A, from pig liver
      microsomes.
AB  - Cytochromes P450 comprise a superfamily of proteins that play a crucial role in
      the biotransformation of numerous chemicals. Purified CYPs can be used e.g. in
      studies on structure or determining the drug metabolism pathways. In this work,
      purification of the porcine CYP1A and CYP2A19 to electrophoretic homogeneity from
      the pig hepatic microsomes using octylamino Sepharose and hydroxylapatite column
      chromatography is reported. The proteins have been clearly recognized by
      commercial antibodies against rat and human CYP1A2 (porcine CYP1A) and human
      CYP2A6 (CYP2A19) respectively, using Western blot. Activities of both enzymes
      were determined by specific substrates, 7-ethoxyresorufin, 7-methoxyresorufin
      (CYP1A) and coumarin (CYP2A19). The isolated enzymes show kinetic parameters
      similar to human counterparts. Taken together, pig cytochromes can be used for
      the testing of veterinary drug metabolism, useful for the determination of drug
      residues in meat of pigs. The results obtained show that the pigs may be a
      suitable model for biotransformation of xenobiotics in humans.

PMID- 19754915
TI  - Antinociceptive effects of epidural buprenorphine or medetomidine, or the
      combination, in conscious cats.
AB  - The aim of this study was to compare the antinociceptive effects of epidural
      buprenorphine (EB), epidural medetomidine (EM) or epidural buprenorphine
      medetomidine (EBM). Eight cats were studied. Thermal thresholds (TT) were
      measured by increasing the temperature of a probe placed on the thorax.
      Mechanical thresholds (MT) were measured through inflation of a modified blood
      pressure bladder to the cat's forelimb. After baseline measurements, EB (0.02
      mg/kg), EM (0.01 mg/kg) or half of the doses of each drug (EBM) were
      administered. Data were analysed using anova (P < 0.05) and 95% confidence
      interval (CI). TT increased from 30 min to 1 h after EB and at 45 min after EM.
      MT increased from 45 min to 2 h after EB, from 15 min to 1 h after EM and at 30,
      45 min and at 2 h after EBM. MT were significantly lower after EB than EM at 30
      min. TT were above the upper 95%CI from 15 min to 24 h after EB, from 15 min to 4
      h after EM and from 15 min to 8 h after EBM. MT were above the upper 95%CI from
      15 min to 5 h, and at 8, 12 and 24 h after EB, from 15 min to 6 h after EM and
      from 15 min to 6 h and at 12 and 24 h after EBM. All treatments had similar
      onset. Overall, EB presented longer period of action than EBM and EM. The same
      magnitude of analgesia was achieved, but with fewer side effects when EBM was
      compared with EM.

PMID- 19754916
TI  - Pharmacokinetics of 4-aminopyridine derivatives in dogs.
AB  - Blockade of potassium channels with 4-aminopryidine (4-AP) restores conduction to
      demyelinated axons and improves function. Unfortunately, 4-AP causes adverse
      effects and its clinical effects are unpredictable and limited. Derivatives of 4
      AP have been tested in models of spinal cord injury in guinea pigs; three
      derivatives (methyl-, ethyl- and t-butyl carbamate derivatives) showed promise.
      This study investigates the safety and pharmacokinetics of these derivatives in
      dogs. Each derivative was administered orally to dogs starting at doses below
      effective doses in guinea pigs, and increasing the dose on sequential days.
      Routine blood work was performed prior to and 24 h after drug administration,
      blood samples were collected at intervals over 24 h after drug administration,
      and dogs were monitored for side effects. Derivative plasma levels were
      determined using high-pressure liquid chromatography. Cerebrospinal fluid (CSF)
      samples were taken to determine CSF levels. No adverse effects were seen even
      when using doses higher than those that improved conduction in spinal cord
      injured guinea pigs. Peak plasma levels occurred at 36.6 (ethyl), 87 (t-butyl)
      and 175 (methyl) min and plasma level was related to drug dose. Penetration of
      the central nervous system (CNS) was good, with CSF levels higher than plasma
      levels for the t-butyl derivative.

PMID- 19754917
TI  - Pharmacokinetics of the injectable formulation of methadone hydrochloride
      administered orally in horses.
AB  - Methadone hydrochloride is a synthetic mu-opioid receptor agonist with potent
      analgesic properties. Oral methadone has been successfully used in human medicine
      and may overcome some limitations of other analgesics in equine species for
      producing analgesia with minimal adverse effects. However, there are no studies
      describing the pharmacokinetics (PK) of oral opioids in horses. The aim of this
      study was to describe the PK of orally administered methadone (0.1, 0.2 and 0.4
      mg/kg) and physical effects in 12 healthy adult horses. Serum methadone
      concentrations were measured by gas chromatography/mass spectrometry at
      predetermined time points for 24 h, and PK parameters were estimated using a
      noncompartmental model. Physical effects were observed and recorded by
      experienced clinicians. No drug toxicity, behavioural or adverse effects were
      observed in the horses. The disposition of methadone followed first order
      elimination and a biphasic serum profile with rapid absorption and elimination
      phases. The PK profile of methadone was characterized by high clearance (Cl/F),
      small volume of distribution (V(d)/F) and short elimination half-life (t(1/2)).
      The mean of the estimated t(1/2) (SD) for each dose (0.1, 0.2 and 0.4 mg/kg) was
      2.2 (35.6), 1.3 (46.1) and 1.5 (40.8), and the mean for the estimated C(max) (SD)
      was 33.9 (6.7), 127.9 (36.0) and 193.5 (65.8) respectively.

PMID- 19754918
TI  - Milk secretion of nitrofurantoin, as a specific BCRP/ABCG2 substrate, in assaf
      sheep: modulation by isoflavones.
AB  - Studies on residues in milk used for human consumption have increased due to
      health concerns and priority interest in the control of potentially risky drugs.
      The protein BCRP/ABCG2, present in the mammary epithelia, actively extrudes drugs
      into milk and can be modulated by isoflavones. Nitrofurantoin is a specific BCRP
      substrate which is actively excreted into milk by this transporter. In this
      research, we studied nitrofurantoin transport into milk in four experimental
      groups: G1-calves fed forage with isoflavones; G2-calves fed forage with
      isoflavones and administered exogenous genistein and daidzein; G3-calves fed
      forage without isoflavones; G4-calves fed forage without isoflavones and
      administered exogenous genistein and daidzein. Results show increased levels of
      nitrofurantoin in milk from calves without isoflavones (G3) and decreased
      nitrofurantoin residues in milk when isoflavones were present, either by forage
      (G1 and G2) or by exogenous administration (G4). The values of C(max) in milk
      were significantly lower in those groups with isoflavones in forage (G1, G2).
      Plasma levels were low and unmodified among the groups. Inter-individual
      variation was high. All these results seem to point to a feasible control of drug
      secretion into milk through isoflavones in the diet when the drug is a good
      BCRP/ABCG2 substrate.

PMID- 19754919
TI  - Plasma buprenorphine concentrations after the application of a 70 microg/h
      transdermal patch in dogs. Preliminary report.
AB  - The objective of the present study was to evaluate the plasma concentrations and
      pharmacokinetics of buprenorphine after transdermal application in dogs (n = 4).
      A 70 microg/h transdermal buprenorphine patch was applied to the ventral abdomen
      of four healthy beagles. Blood samples were collected through a preplaced jugular
      catheter before and at 1, 2, 4, 8, 12, 24, 36, 48 and every 6 h until 108 h after
      the patch application. Plasma buprenorphine concentrations were measured using a
      (125)I-labelled radioimmunoassay (RIA) assay. No adverse effects were observed in
      any of the dogs. Concentrations of buprenorphine were detected in plasma after
      the application of the transdermal buprenorphine patch on the four experimental
      animals. Buprenorphine plasma concentrations increased during the first 36 h and
      then remained in the 0.7-1.0 ng/mL range during the study period. A decrease in
      plasma buprenorphine concentration was not observed during the study. Although
      analgesia could not be demonstrated the present study shows the ability of
      buprenorphine transdermal delivery systems developed for human use to deliver
      measurable concetrations of buprenorphine in dogs.

PMID- 19754920
TI  - Oral bioavailability and pharmacokinetic profile of the amoxicillin-clavulanic
      acid combination after intravenous and oral gavage administration in broiler
      chickens.

PMID- 19754921
TI  - Plasma pharmacokinetics of alfaxalone in both premedicated and unpremedicated
      Greyhound dogs after single, intravenous administration of Alfaxan at a clinical
      dose.

PMID- 19754922
TI  - Somatostatin receptor subtypes 2 and 5 mediate inhibition of egg yolk-induced
      gall bladder emptying in mice.
AB  - BACKGROUND: Somatostatin inhibits gall bladder contraction. Impaired gall bladder
      emptying is associated with gall bladder stone formation. The incidence of
      cholecystolithiasis is high in patients treated with a somatostatin agonist
      octreotide, which predominantly interacts with somatostatin receptor subtype 2
      (SSTR2). Therefore, it is believed that SSTR2 regulates gall bladder contraction;
      however, evidence has not been provided. Here, we evaluate the effects of SSTR1
      SSTR5-selective agonists on egg yolk-induced gall bladder contraction in mice.
      METHODS: Homozygous deletion of SSTR2 and SSTR5 was generated by cross-mating of
      SSTR2(-/-) with SSTR5(-/-) mice. Mice of different genotypes were injected with
      SSTR1-5-selective agonists or octreotide 15 min before induction of gall bladder
      emptying by egg yolk. One hour later, gall bladders were removed and weighed. KEY
      RESULTS: Egg yolk-reduced gall bladder weights in all mice, irrespective of their
      genotype. Octreotide was the most potent inhibitor of gall bladder emptying in
      wild-type mice. In contrast, agonists with high selectivity for SSTR2 or SSTR5
      inhibited gall bladder emptying by approximately 50-60%, whereas SSTR1-, SSTR3-
      and SSTR4-selective agonists failed to influence gall bladder contraction. In
      SSTR2(-/-) mice, octreotide and an SSTR5-selective agonist inhibited gall bladder
      emptying by approximately 50%, whereas SSTR2-selective agonists were inactive.
      Octreotide inhibited gall bladder emptying in SSTR5(-/-) mice by approximately
      50%, without any effect in SSTR2(-/-)/SSTR5(-/-) mice. CONCLUSIONS & INFERENCES:
      Our study provides evidence for the role of SSTR2 and SSTR5 in regulating gall
      bladder emptying in mice.

PMID- 19754923
TI  - A score test for association of a longitudinal marker and an event with missing
      data.
AB  - Often clinical studies periodically record information on disease progression as
      well as results from laboratory studies that are believed to reflect the
      progressing stages of the disease. A primary aim of such a study is to determine
      the relationship between the lab measurements and a disease progression. If there
      were no missing or censored data, these analyses would be straightforward.
      However, often patients miss visits, and return after their disease has
      progressed. In this case, not only is their progression time interval censored,
      but their lab test series is also incomplete. In this article, we propose a
      simple test for the association between a longitudinal marker and an event time
      from incomplete data. We derive the test using a very intuitive technique of
      calculating the expected complete data score conditional on the observed
      incomplete data (conditional expected score test, CEST). The problem was
      motivated by data from an observational study of patients with diabetes.

PMID- 19754924
TI  - Associated cancers in parents and offspring of polycythaemia vera and
      myelofibrosis patients.
AB  - Polycythaemia vera (PV) and primary myelofibrosis (MF) show concordant familial
      clustering but limited population level data are available on the aggregation of
      other discordant neoplasms in these families. We used the Swedish Family-Cancer
      Database to assess risks for VP and MF in families of cancer patients. A total of
      3530 first PV and 1606 MF patients were identified, with high concordant familial
      risks. Several discordant familial associations were found for PV (acute myeloid
      leukaemia, Hodgkin disease, prostate and bladder cancers) or for MF (chronic
      lymphatic leukaemia, colorectal, kidney and cervical cancers) or for both
      (nervous system, eye and endocrine tumours).

PMID- 19754925
TI  - HECTD2, a candidate susceptibility gene for Alzheimer's disease on 10q.
AB  - BACKGROUND: Late onset Alzheimer's disease (LOAD) is a neurodegenerative disorder
      characterised by the deposition of amyloid plaques and neurofibrillary tangles in
      the brain and is the major cause of dementia. Multiple genetic loci, including
      10q, have been implicated in LOAD but to date, with the exception of APOE, the
      underlying genes have not been identified. HECTD2 maps to 10q and has been
      implicated in susceptibility to human prion diseases which are also
      neurodegenerative conditions associated with accumulation of misfolded host
      proteins. In this study we test whether the HECTD2 susceptibility allele seen in
      prion disease is also implicated in LOAD. METHODS: DNA from 320 individuals with
      Alzheimer's disease and 601 controls were genotyped for a HECTD2 intronic tagging
      SNP, rs12249854 (A/T). Groups were further analysed following stratification by
      APOE genotype. RESULTS: The rs12249854 minor allele (A) frequency was higher
      (5.8%) in the Alzheimer's disease group as compared to the controls (3.9%),
      however, this was not statistically significant (P = 0.0668). No significant
      difference was seen in minor allele frequency in the presence or absence of the
      APOE epsilon4 allele. CONCLUSION: The common haplotypes of HECTD2, tagged by
      rs12249854, are not associated with susceptibility to LOAD.

PMID- 19754926
TI  - The antibacterial properties of Malaysian tualang honey against wound and enteric
      microorganisms in comparison to manuka honey.
AB  - BACKGROUND: Antibiotic resistance of bacteria is on the rise, thus the discovery
      of alternative therapeutic agents is urgently needed. Honey possesses therapeutic
      potential, including wound healing properties and antimicrobial activity.
      Although the antimicrobial activity of honey has been effectively established
      against an extensive spectrum of microorganisms, it differs depending on the type
      of honey. To date, no extensive studies of the antibacterial properties of
      tualang (Koompassia excelsa) honey on wound and enteric microorganisms have been
      conducted. The objectives of this study were to conduct such studies and to
      compare the antibacterial activity of tualang honey with that of manuka honey.
      METHODS: Using a broth dilution method, the antibacterial activity of tualang
      honey against 13 wound and enteric microorganisms was determined; manuka honey
      was used as the control. Different concentrations of honey [6.25-25% (w/v)] were
      tested against each type of microorganism. Briefly, two-fold dilutions of honey
      solutions were tested to determine the minimum inhibitory concentration (MIC)
      against each type of microorganism, followed by more assays within a narrower
      dilution range to obtain more precise MIC values. MICs were determined by both
      visual inspection and spectrophotometric assay at 620 nm. Minimum bactericidal
      concentration (MBC) also was determined by culturing on blood agar plates.
      RESULTS: By visual inspection, the MICs of tualang honey ranged from 8.75% to 25%
      compared to manuka honey (8.75-20%). Spectrophotometric readings of at least 95%
      inhibition yielded MIC values ranging between 10% and 25% for both types of
      honey. The lowest MBC for tualang honey was 20%, whereas that for manuka honey
      was 11.25% for the microorganisms tested. The lowest MIC value (8.75%) for both
      types of honey was against Stenotrophomonas maltophilia. Tualang honey had a
      lower MIC (11.25%) against Acinetobacter baumannii compared to manuka honey
      (12.5%). CONCLUSION: Tualang honey exhibited variable activities against
      different microorganisms, but they were within the same range as those for manuka
      honey. This result suggests that tualang honey could potentially be used as an
      alternative therapeutic agent against certain microorganisms, particularly A.
      baumannii and S. maltophilia.

PMID- 19754927
TI  - Hemoglobin levels and anemia evaluation during pregnancy in the highlands of
      Tibet: a hospital-based study.
AB  - BACKGROUND: Anemia is regarded as a major risk factor for unfavorable pregnancy
      outcomes, but there have been no previous studies describing the pattern of
      hemoglobin concentration during pregnancy in Tibet and the relationship between
      altitude and Hb concentration in the pregnant women living in Tibet still has not
      been clearly established. The main objectives of this study were to study the
      hemoglobin levels and prevalence of anemia among pregnant women living in the
      highlands of Tibet and to evaluate potential associations of hemoglobin and
      anemia with women's characteristics. METHODS: The hospital-based study was
      conducted in 380 pregnant women. Their blood samples were tested and related
      sociodemographic information was collected. Multiple linear regression model and
      multiple logistic regression model were used to assess the association of
      pregnant women's characteristics with hemoglobin level and the occurrence of
      anemia. Centers for Disease Control (CDC), Dirren et al. and Dallman et al.
      methods were used to adjust the hemoglobin measurements based on altitude for
      estimating the prevalence of anemia. RESULTS: The mean hemoglobin concentration
      was 127.6 g/L (range: 55.0-190.0 g/L). Prevalence rate of anemia in this study
      was 70.0%, 77.9% and 41.3%, respectively for three altitude-correction methods
      for hemoglobin (CDC method, Dirren et al. method, and Dallman et al. method).
      Gestational age, ethnicity, residence and income were significantly associated
      with the hemoglobin concentration and prevalence of anemia in the study
      population. Specially, the hemoglobin concentration of pregnant women decreased
      with increase in gestational age. CONCLUSION: The hemoglobin level was low and
      prevalence rate of anemia was high among pregnant women in Lhasa, Tibet.
      Gestational age, ethnicity, residence and income were found to be significantly
      associated with the hemoglobin level and the occurrence of anemia in the study
      population.

PMID- 19754928
TI  - Correlates of quality of life of pre-obese and obese patients: a pharmacy-based
      cross-sectional survey.
AB  - BACKGROUND: The correlates of quality of life (QOL), as measured by the OSQOL
      questionnaire were investigated in a convenience sample of overweight patients
      recruited in pharmacies. METHODS: A convenience sample of patients with a Body
      Mass Index > or = 28 kg/m(2) were recruited in community-based pharmacies.
      Baseline characteristics and QOL dimensions (1-Physical state, 2-Vitality-desire
      to do things, 3-Relations with others, 4-Psychological state) were reported in
      self-completed questionnaires from which the risk of obtaining a low QOL was
      assessed for each dimension. RESULTS: QOL was inadequate for all dimensions in
      the 494 patients included in the study (median age = 61, 48% women, 21%
      professional persons/top executives). Older pre-obese and obese patients were
      more likely to report impaired physical functioning (OR = 2.02, 95%CI = [1.10
      3.70]), but were less severely affected socially (OR = 0.32, 95%CI = [0.15
      0.69]). Pre-obese and obese professional persons and top executives showed better
      physical capabilities (OR = 0.35, 95%CI = [0.15-0.81]) and increased vitality (OR
      = 0.47, 95%CI = [0.23-0.95]). Overall, men's psychological state was better than
      females' (OR = 0.46, 95%CI = [0.25-0.82]). A body-mass index > or = 35 kg/m(2)
      was significantly associated with poorer QOL scores on physical, relational and
      psychological dimensions. CONCLUSION: Our data highlighted the influence of the
      severity of excess weight, gender, age and socioeconomic status on QOL. These
      factors should be taken into account when interpreting QOL in pre-obese and obese
      persons.

PMID- 19754929
TI  - Effects of two common polymorphisms in the 3' untranslated regions of estrogen
      receptor beta on mRNA stability and translatability.
AB  - BACKGROUND: The present study represents the first attempt to functionally
      characterize two common single nucleotide polymorphisms (SNPs) in the
      3'untranslated regions (3'UTRs) of estrogen receptor beta (ERbeta), focusing on
      the differences between alleles with regard to mRNA stability and
      translatability. These two ERbeta SNPs have been investigated for association
      with disease in a large number of reports. RESULTS: Here we examined allelic
      expression in breast tumor samples from heterozygous individuals. A significant
      difference in mRNA levels of the two alleles was observed for one of the SNPs. A
      cell model system was employed to further investigate potential molecular effects
      of the two SNPs. We used a modified plasmid, containing the ERbeta promoter and
      ERbeta 3'UTRs which include the different alleles of investigated SNPs.
      Quantitative Real-Time PCR was used to determine mRNA levels after inhibition of
      transcription by actinomycin D, and a luciferase assay was used to determine
      protein levels. The obtained results suggested that there was no difference in
      mRNA stability or translatability between the alleles of investigated SNPs.
      CONCLUSION: Our results indicate that observed associations between ERbeta 3'UTR
      SNPs and disease susceptibility are due to linkage disequilibrium with another
      gene variant, rather than the variant itself being the susceptibility factor.

PMID- 19754930
TI  - Cancer incidence in the population exposed to dioxin after the "Seveso accident":
      twenty years of follow-up.
AB  - BACKGROUND: The Seveso, Italy accident in 1976 caused the contamination of a
      large population by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Possible long
      term effects have been examined through mortality and cancer incidence studies.
      We have updated the cancer incidence study which now covers the period 1977-96.
      METHODS: The study population includes subjects resident at the time of the
      accident in three contaminated zones with decreasing TCDD soil levels (zone A,
      very high; zone B, high; zone R, low) and in a surrounding non-contaminated
      reference territory. Gender-, age-, and period-adjusted rate ratios (RR) and 95%
      confidence intervals (95% CI) were calculated by using Poisson regression for
      subjects aged 0-74 years. RESULTS: All cancer incidence did not differ from
      expectations in any of the contaminated zones. An excess of lymphatic and
      hematopoietic tissue neoplasms was observed in zones A (four cases; RR, 1.39; 95%
      CI, 0.52-3.71) and B (29 cases; RR, 1.56; 95% CI, 1.07-2.27) consistent with the
      findings of the concurrent mortality study. An increased risk of breast cancer
      was detected in zone A females after 15 years since the accident (five cases, RR,
      2.57; 95% CI, 1.07-6.20). No cases of soft tissue sarcomas occurred in the most
      exposed zones (A and B, 1.17 expected). No cancer cases were observed among
      subjects diagnosed with chloracne early after the accident. CONCLUSION: The
      extension of the Seveso cancer incidence study confirmed an excess risk of
      lymphatic and hematopoietic tissue neoplasms in the most exposed zones. No clear
      pattern by time since the accident and zones was evident partly because of the
      low number of cases. The elevated risk of breast cancer in zone A females after
      15 years since the accident deserves further and thorough investigation. The
      follow-up is continuing in order to cover the long time period (even decades)
      usually elapsing from exposure to carcinogenic chemicals and disease occurrence.

PMID- 19754931
TI  - Effect of an oral supplementation with a proprietary melon juice concentrate
      (Extramel) on stress and fatigue in healthy people: a pilot, double-blind,
      placebo-controlled clinical trial.
AB  - BACKGROUND: Recent studies have demonstrated a correlation between perceived
      stress and oxidative stress. As SOD is the main enzyme of the enzymatic
      antioxidant defence system of the body, we evaluated the effect of an oral daily
      intake of a proprietary melon juice concentrate rich in SOD (EXTRAMEL) on the
      signs and symptoms of stress and fatigue in healthy volunteers. METHODS: This
      randomized, double blind, placebo controlled clinical study was conducted with
      seventy healthy volunteers aged between 30 and 55 years, who feel daily stress
      and fatigue. They took the dietary supplement based on the melon juice
      concentrate (10 mg Extramel corresponding to 140 IU SOD per capsule) or a placebo
      one time daily during 4 weeks. Stress and fatigue were measured using four
      observational psychometric scales: FARD, PSS-14, SF-12 and Epworth scale. The
      study was conducted by Isoclin, a clinical research organization, located in
      Poitiers, France. RESULTS: No adverse effect was noted. The supplementation with
      the proprietary melon juice concentrate bringing 140 IU SOD/day significantly
      improved signs and symptoms of stress and fatigue linked to performance, physical
      (pain, sleep troubles), cognitive (concentration, weariness, sleep troubles) or
      behavioural (attitude, irritability, difficulty of contact) compared to the
      placebo. In the same way, quality of life and perceived stress were significantly
      improved with SOD supplementation. CONCLUSION: This pilot study showed that an
      oral supplementation with a proprietary melon juice concentrate rich in SOD may
      have a positive effect on several signs and symptoms of perceived stress and
      fatigue.

PMID- 19754932
TI  - The role of left and right hemispheres in the comprehension of idiomatic
      language: an electrical neuroimaging study.
AB  - BACKGROUND: The specific role of the two cerebral hemispheres in processing
      idiomatic language is highly debated. While some studies show the involvement of
      the left inferior frontal gyrus (LIFG), other data support the crucial role of
      right-hemispheric regions, and particularly of the middle/superior temporal area.
      Time-course and neural bases of literal vs. idiomatic language processing were
      compared. Fifteen volunteers silently read 360 idiomatic and literal Italian
      sentences and decided whether they were semantically related or unrelated to a
      following target word, while their EEGs were recorded from 128 electrodes. Word
      length, abstractness and frequency of use, sentence comprehensibility,
      familiarity and cloze probability were matched across classes. RESULTS:
      Participants responded more quickly to literal than to idiomatic sentences,
      probably indicating a difference in task difficulty. Occipito/temporal N2
      component had a greater amplitude in response to idioms between 250-300 ms.
      Related swLORETA source reconstruction revealed a difference in the activation of
      the left fusiform gyrus (FG, BA19) and medial frontal gyri for the contrast
      idiomatic-minus-literal. Centroparietal N400 was much larger to idiomatic than to
      literal phrases (360-550 ms). The intra-cortical generators of this effect
      included the left and right FG, the left cingulate gyrus, the right limbic area,
      the right MTG (BA21) and the left middle frontal gyrus (BA46). Finally, an
      anterior late positivity (600-800 ms) was larger to idiomatic than literal
      phrases. ERPs also showed a larger right centro-parietal N400 to associated than
      non-associated targets (not differing as a function of sentence type), and a
      greater right frontal P600 to idiomatic than literal associated targets.
      CONCLUSION: The data indicate bilateral involvement of both hemispheres in idiom
      comprehension, including the right MTG after 350 ms and the right medial frontal
      gyrus in the time windows 270-300 and 500-780 ms. In addition, the activation of
      left and right limbic regions (400-450 ms) suggests that they have a role in the
      emotional connotation of colourful idiomatic language. The data support the view
      that there is direct access to the idiomatic meaning of figurative language, not
      dependent on the suppression of its literal meaning, for which the LIFG was
      previously thought to be responsible.

PMID- 19754933
TI  - Reverse-engineering the Arabidopsis thaliana transcriptional network under
      changing environmental conditions.
AB  - BACKGROUND: Understanding the molecular mechanisms plants have evolved to adapt
      their biological activities to a constantly changing environment is an intriguing
      question and one that requires a systems biology approach. Here we present a
      network analysis of genome-wide expression data combined with reverse-engineering
      network modeling to dissect the transcriptional control of Arabidopsis thaliana.
      The regulatory network is inferred by using an assembly of microarray data
      containing steady-state RNA expression levels from several growth conditions,
      developmental stages, biotic and abiotic stresses, and a variety of mutant
      genotypes. RESULTS: We show that the A. thaliana regulatory network has the
      characteristic properties of hierarchical networks. We successfully applied our
      quantitative network model to predict the full transcriptome of the plant for a
      set of microarray experiments not included in the training dataset. We also used
      our model to analyze the robustness in expression levels conferred by network
      motifs such as the coherent feed-forward loop. In addition, the meta-analysis
      presented here has allowed us to identify regulatory and robust genetic
      structures. CONCLUSIONS: These data suggest that A. thaliana has evolved high
      connectivity in terms of transcriptional regulation among cellular functions
      involved in response and adaptation to changing environments, while gene networks
      constitutively expressed or less related to stress response are characterized by
      a lower connectivity. Taken together, these findings suggest conserved regulatory
      strategies that have been selected during the evolutionary history of this
      eukaryote.

PMID- 19754934
TI  - Blood pressure control and components of the metabolic syndrome: the GOOD survey.
AB  - BACKGROUND: The GOOD (Global Cardiometabolic Risk Profile in Patients with
      Hypertension Disease) survey showed that blood pressure control was significantly
      worse in hypertensive patients with metabolic syndrome and/or diabetes mellitus
      than in those with essential hypertension only. This analysis aimed to
      investigate which components of the metabolic syndrome are primarily associated
      with poor blood pressure control. METHODS: The GOOD survey was designed as an
      observational cross-sectional survey in 12 European countries to assess the
      cardiometabolic risk profile in patients with essential hypertension.
      Investigators were randomly selected from a list of general practitioners (70% of
      investigators) and a list of specialists such as internists, cardiologists and
      hypertension specialists (30% of investigators). Data from 3,280 outpatients with
      hypertension, aged at least 30 years who were receiving antihypertensive
      treatment or had newly diagnosed hypertension according to the European Society
      of Hypertension and the European Society of Cardiology criteria, were included in
      the analyses. Blood pressure control, body mass index (BMI), waist circumference,
      serum triglycerides, total and high density lipoprotein (HDL) cholesterol
      measurements were compared in patients with diabetes mellitus and metabolic
      syndrome, with diabetes mellitus only, with metabolic syndrome only, and with
      neither metabolic syndrome nor diabetes mellitus. RESULTS: The highest blood
      pressure values were found in patients with metabolic syndrome with or without
      diabetes mellitus. Blood pressure was significantly lower in patients with
      diabetes mellitus only. The highest BMI, waist circumference and serum
      triglycerides, and the lowest HDL cholesterol levels among the groups studied
      occurred in patients with metabolic syndrome, either with or without diabetes
      mellitus. CONCLUSION: Among the components of the metabolic syndrome, it is not
      impaired glucose tolerance which is associated with the poor response to
      antihypertensive treatment. Instead, visceral obesity and dyslipidemia components
      of the metabolic syndrome, i.e. hypertriglyceridemia and low HDL cholesterol
      levels, are associated with resistance to antihypertensive treatment.

PMID- 19754935
TI  - An open-label, 1-year extension study of the long-term safety and efficacy of
      once-daily OROS(R) hydromorphone in patients with chronic cancer pain.
AB  - BACKGROUND: Opioid analgesics have proven efficacy in the short-term management
      of chronic cancer pain, but data on their long-term use is more limited. OROS(R)
      hydromorphone is a controlled-release formulation of oral hydromorphone that may
      be particularly well suited to long-term management of chronic cancer pain
      because it provides stable plasma concentrations and consistent analgesia with
      convenient once-daily dosing. The objective of this study (DO-118X) was to
      characterise the pain control achieved with long-term repeated dosing of OROS(R)
      hydromorphone in patients with chronic cancer pain. METHODS: In this multicentre,
      phase III, open-label, single treatment, 1-year extension study, OROS(R)
      hydromorphone was administered to 68 patients with moderate-to-severe chronic
      cancer pain, who had successfully completed a short-term equivalence study, and
      whose pain was controlled with a stable dose of medication (>/= 8 mg OROS(R)
      hydromorphone or equivalent controlled-release morphine). Patients were started
      on the dose of OROS(R) hydromorphone equivalent to the opioid dose on which they
      achieved dose-stable pain control in the equivalence study; dose adjustments were
      made as necessary and breakthrough pain medication was permitted. Efficacy was
      assessed with the Brief Pain Inventory (BPI) and patient and investigator global
      evaluations of treatment effectiveness. No formal statistical analysis was done.
      RESULTS: The mean (standard deviation) duration of exposure to study medication
      was 139 (129.9) days and the mean (standard deviation) average daily consumption
      of OROS(R) hydromorphone was 43.7 (28.14) mg/day. All scores were maintained at a
      mild to moderate severity throughout the study; however, BPI scores for pain at
      its worst, pain at its least, pain on average, pain right now, and pain relief
      were slightly worsened at end point compared with baseline. Mean BPI pain
      interference with daily activities and patient and investigator global evaluation
      scores also remained generally stable. Treatment effectiveness was rated as fair
      to good throughout the study. The most frequently reported adverse events were
      nausea (n = 24, 35.3%), constipation (n = 22, 32.4%), and vomiting (n = 15,
      22.1%). CONCLUSION: The results of this extension study suggest that long-term
      repeated dosing with once-daily OROS(R) hydromorphone can be beneficial in the
      continuing management of persistent, moderate-to-severe cancer pain.

PMID- 19754936
TI  - Cardiorespiratory effects of venous lipid micro embolization in an experimental
      model of mediastinal shed blood reinfusion.
AB  - BACKGROUND: Retransfusion of the patient's own blood during surgery is used to
      reduce the need for allogenic blood transfusion. It has however been found that
      this blood contains lipid particles, which form emboli in different organs if the
      blood is retransfused on the arterial side. In this study, we tested whether
      retransfusion of blood containing lipid micro-particles on the venous side in a
      porcine model will give hemodynamic effects. METHODS: Seven adult pigs were used.
      A shed blood surrogate containing 400 ml diluted blood and 5 ml radioactive
      triolein was produced to generate a lipid embolic load. The shed blood surrogate
      was rapidly (<2 minutes) retransfused from a transfusion bag to the right atrium
      under general anesthesia. The animals' arterial, pulmonary, right and left atrial
      pressure were monitored, together with cardiac output and deadspace. At the end
      of the experiment, an increase in cardiac output and pulmonary pressure was
      pharmacologically induced to try to flush out lipid particles from the lungs.
      RESULTS: A more than 30-fold increase in pulmonary vascular resistance was
      observed, with subsequent increase in pulmonary artery pressure, and decrease in
      cardiac output and arterial pressure. This response was transient, but was
      followed by a smaller, persistent increase in pulmonary vascular resistance. Only
      a small portion of the infused triolein passed the lungs, and only a small
      fraction could be recirculated by increasing cardiac output and pulmonary
      pressure. CONCLUSION: Infusion of blood containing lipid micro-emboli on the
      venous side leads to acute, severe hemodynamic responses that can be life
      threatening. Lipid particles will be trapped in the lungs, leading to persistent
      effects on the pulmonary vascular resistance.

PMID- 19754937
TI  - Isolated liver transplantation for treatment of liver failure secondary to
      intestinal failure.
AB  - Intestinal Failure is a permanent loss of digestive and absorptive functions as
      a consequence of short bowel syndrome and/or other primary intestinal conditions.
      Patients with intestinal failure (IF) require long term parenteral nutrition to
      survive. The only alternative to parenteral nutrition is intestinal
      transplantation which still entails high mortality. Children with intestinal
      failure on parenteral nutrition may develop liver failure (LF), as a consequence
      of central line infections and other conditions. In children with both
      irreversible IF and LF a combined transplantation is generally considered.
      Despite low survival rate, combined liver/intestine transplantation is associated
      to better intestinal graft survival and lower incidence and severity of rejection
      compared to isolated small bowel transplantation. Recently, isolated liver
      transplantation was proposed in children with IF and LF. This procedure may have
      a higher survival probability compared to isolated intestinal transplant, it may
      allow progressive weaning from PN in children in whom the remnant intestine has
      the potential for adaptation and offer a timely solution in children for whom
      intestinal graft is not immediately available. This innovative approach may prove
      a better option compared to combined transplantation in both the short and long
      term.

PMID- 19754938
TI  - Pathophysiology of the systemic inflammatory response after major accidental
      trauma.
AB  - BACKGROUND: The purpose of the present study was to describe the pathophysiology
      of the systemic inflammatory response after major trauma and the timing of final
      reconstructive surgery. METHODS: An unsystematic review of the medical literature
      was performed and articles pertaining to the inflammatory response to trauma were
      obtained. The literature selected was based on the preference and clinical
      expertise of authors. DISCUSSION: The inflammatory response consists of hormonal
      metabolic and immunological components and the extent correlates with the
      magnitude of the tissue injury. After trauma and uncomplicated surgery a delicate
      balance between pro- and anti-inflammatory mediators is observed. Trauma patients
      are, however, often exposed, not only to the trauma, but to several events in the
      form of initial surgery and later final reconstructive surgery. In this case
      immune paralysis associated with increased risk of infection might develop. The
      inflammatory response is normalized 3 weeks following trauma. It has been
      proposed that the final reconstructive surgery should be postponed until the
      inflammatory response is normalized. This statement is however not based on
      clinical trials. CONCLUSION: Postponement of final reconstructive surgery until
      the inflammatory is normalized should be based on prospective randomized trials.

PMID- 19754939
TI  - Comparative in vivo gene expression of the closely related bacteria Photorhabdus
      temperata and Xenorhabdus koppenhoeferi upon infection of the same insect host,
      Rhizotrogus majalis.
AB  - BACKGROUND: Photorhabdus and Xenorhabdus are Gram-negative, phylogenetically
      related, enterobacteria, forming mutualism with the entomopathogenic nematodes
      Heterorhabditis and Steinernema, respectively. The mutualistic bacteria living in
      the intestines of the nematode infective juveniles are pathogenic to the insect
      upon release by the nematodes into the insect hemolymph. Such a switch needs
      activation of genes that promote bacterial virulence. We studied in vivo gene
      expression in Photorhabdus temperata and Xenorhabdus koppenhoeferi upon infection
      of the white grub Rhizotrogus majalis using selective capture of transcribed
      sequences technique. RESULTS: A total of 40 genes in P. temperata and 39 in X.
      koppenhoeferi were found to be upregulated in R. majalis hemolymph at 24 h post
      infection. Genomic presence or upregulation of these genes specific in either one
      of the bacterium was confirmed by the assay of comparative hybridization, and the
      changes of randomly selected genes were further validated by quantitative real
      time PCR. The identified genes could be broadly divided into seven functional
      groups including cell surface structure, regulation, virulence and secretion,
      stress response, intracellular metabolism, nutrient scavenging, and unknown. The
      two bacteria shared more genes in stress response category than any other
      functional group. More than 60% of the identified genes were uniquely induced in
      either bacterium suggesting vastly different molecular mechanisms of
      pathogenicity to the same insect host. In P. temperata lysR gene encoding
      transcriptional activator was induced, while genes yijC and rseA encoding
      transcriptional repressors were induced in X. koppenhoeferi. Lipopolysaccharide
      synthesis gene lpsE was induced in X. koppenhoeferi but not in P. temperata.
      Except tcaC and hemolysin related genes, other virulence genes were different
      between the two bacteria. Genes involved in TCA cycle were induced in P.
      temperata whereas those involved in glyoxylate pathway were induced in X.
      koppenhoeferi, suggesting differences in metabolism between the two bacteria in
      the same insect host. Upregulation of genes encoding different types of nutrient
      uptake systems further emphasized the differences in nutritional requirements of
      the two bacteria in the same insect host. Photorhabdus temperata displayed
      upregulation of genes encoding siderophore-dependent iron uptake system, but X.
      koppenhoeferi upregulated genes encoding siderophore-independent ion uptake
      system. Photorhabdus temperata induced genes for amino acid acquisition but X.
      koppenhoeferi upregulated malF gene, encoding a maltose uptake system. Further
      analyses identified possible mechanistic associations between the identified gene
      products in metabolic pathways, providing an interactive model of pathogenesis
      for each bacterium species. CONCLUSION: This study identifies set of genes
      induced in P. temperata and X. koppenhoeferi upon infection of R. majalis, and
      highlights differences in molecular features used by these two closely related
      bacteria to promote their pathogenicity in the same insect host.

PMID- 19754940
TI  - Atherosclerosis profile and incidence of cardiovascular events: a population
      based survey.
AB  - BACKGROUND: Atherosclerosis is a chronic progressive disease often presenting as
      clinical cardiovascular disease (CVD) events. This study evaluated the
      characteristics of individuals with a diagnosis of atherosclerosis and estimated
      the incidence of CVD events to assist in the early identification of high-risk
      individuals. METHODS: Respondents to the US SHIELD baseline survey were followed
      for 2 years to observe incident self-reported CVD. Respondents had subclinical
      atherosclerosis if they reported a diagnosis of narrow or blocked
      arteries/carotid artery disease without a past clinical CVD event (heart attack,
      stroke or revascularization). Characteristics of those with atherosclerosis and
      incident CVD were compared with those who did not report atherosclerosis at
      baseline but had CVD in the following 2 years using chi-square tests. Logistic
      regression model identified characteristics associated with atherosclerosis and
      incident events. RESULTS: Of 17,640 respondents, 488 (2.8%) reported having
      subclinical atherosclerosis at baseline. Subclinical atherosclerosis was
      associated with age, male gender, dyslipidemia, circulation problems,
      hypertension, past smoker, and a cholesterol test in past year (OR = 2.2) [all p
      < 0.05]. Incident CVD was twice as high in respondents with subclinical
      atherosclerosis (25.8%) as in those without atherosclerosis or clinical CVD
      (12.2%). In individuals with subclinical atherosclerosis, men (RR = 1.77, p =
      0.050) and individuals with circulation problems (RR = 2.36, p = 0.003) were at
      greatest risk of experiencing CVD events in the next 2 years. CONCLUSION: Self
      report of subclinical atherosclerosis identified an extremely high-risk group
      with a >25% risk of a CVD event in the next 2 years. These characteristics may be
      useful for identifying individuals for more aggressive diagnostic and therapeutic
      efforts.

PMID- 19754941
TI  - Determinants of use of maternal health services in Nigeria--looking beyond
      individual and household factors.
AB  - BACKGROUND: Utilization of maternal health services is associated with improved
      maternal and neonatal health outcomes. Considering global and national interests
      in the Millennium Development Goal and Nigeria's high level of maternal
      mortality, understanding the factors affecting maternal health use is crucial.
      Studies on the use of maternal care services have largely overlooked community
      and other contextual factors. This study examined the determinants of maternal
      services utilization in Nigeria, with a focus on individual, household, community
      and state-level factors. METHODS: Data from the 2005 National HIV/AIDS and
      Reproductive Health Survey - an interviewer-administered nationally
      representative survey - were analyzed to identify individual, household and
      community factors that were significantly associated with utilization of maternal
      care services among 2148 women who had a baby during the five years preceding the
      survey. In view of the nested nature of the data, we used multilevel analytic
      methods and assessed state-level random effects. RESULTS: Approximately three
      fifths (60.3%) of the mothers used antenatal services at least once during their
      most recent pregnancy, while 43.5% had skilled attendants at delivery and 41.2%
      received postnatal care. There are commonalities and differences in the
      predictors of the three indicators of maternal health service utilization.
      Education is the only individual-level variable that is consistently a
      significant predictor of service utilization, while socio-economic level is a
      consistent significant predictor at the household level. At the community level,
      urban residence and community media saturation are consistently strong
      predictors. In contrast, some factors are significant in predicting one or more
      of the indicators of use but not for all. These inconsistent predictors include
      some individual level variables (the woman's age at the birth of the last child,
      ethnicity, the notion of ideal family size, and approval of family planning), a
      community-level variable (prevalence of the small family norm in the community),
      and a state-level variable (ratio of PHC to the population). CONCLUSION: Factors
      influencing maternal health services utilization operate at various levels -
      individual, household, community and state. Depending on the indicator of
      maternal health services, the relevant determinants vary. Effective interventions
      to promote maternal health service utilization should target the underlying
      individual, household, community and policy-level factors. The interventions
      should reflect the relative roles of the various underlying factors.

PMID- 19754942
TI  - The development, design, testing, refinement, simulation and application of an
      evaluation framework for communities of practice and social-professional
      networks.
AB  - BACKGROUND: Communities of practice and social-professional networks are
      generally considered to enhance workplace experience and enable organizational
      success. However, despite the remarkable growth in interest in the role of
      collaborating structures in a range of industries, there is a paucity of
      empirical research to support this view. Nor is there a convincing model for
      their systematic evaluation, despite the significant potential benefits in
      answering the core question: how well do groups of professionals work together
      and how could they be organised to work together more effectively? This research
      project will produce a rigorous evaluation methodology and deliver supporting
      tools for the benefit of researchers, policymakers, practitioners and consumers
      within the health system and other sectors. Given the prevalence and importance
      of communities of practice and social networks, and the extent of investments in
      them, this project represents a scientific innovation of national and
      international significance. METHODS AND DESIGN: Working in four conceptual phases
      the project will employ a combination of qualitative and quantitative methods to
      develop, design, field-test, refine and finalise an evaluation framework. Once
      available the framework will be used to evaluate simulated, and then later
      existing, health care communities of practice and social-professional networks to
      assess their effectiveness in achieving desired outcomes. Peak stakeholder groups
      have agreed to involve a wide range of members and participant organisations, and
      will facilitate access to various policy, managerial and clinical networks.
      DISCUSSION: Given its scope and size, the project represents a valuable
      opportunity to achieve breakthroughs at two levels; firstly, by introducing novel
      and innovative aims and methods into the social research process and, secondly,
      through the resulting evaluation framework and tools. We anticipate valuable
      outcomes in the improved understanding of organisational performance and delivery
      of care. The project's wider appeal lies in transferring this understanding to
      other health jurisdictions and to other industries and sectors, both nationally
      and internationally. This means not merely publishing the results, but
      contextually interpreting them, and translating them to advance the knowledge
      base and enable widespread institutional and organisational application.

PMID- 19754943
TI  - DNA vaccine containing the mycobacterial hsp65 gene prevented insulitis in MLD
      STZ diabetes.
AB  - BACKGROUND: Our group previously demonstrated that a DNA plasmid encoding the
      mycobacterial 65-kDa heat shock protein (DNA-HSP65) displayed prophylactic and
      therapeutic effect in a mice model for tuberculosis. This protection was
      attributed to induction of a strong cellular immunity against HSP65. As specific
      immunity to HSP60 family has been detected in arthritis, multiple sclerosis and
      diabetes, the vaccination procedure with DNA-HSP65 could induce a cross-reactive
      immune response that could trigger or worsen these autoimmune diseases. METHODS:
      In this investigation was evaluated the effect of a previous vaccination with DNA
      HSP65 on diabetes development induced by Streptozotocin (STZ). C57BL/6 mice
      received three vaccine doses or the corresponding empty vector and were then
      injected with multiple low doses of STZ. RESULTS: DNA-HSP65 vaccination protected
      mice from STZ induced insulitis and this was associated with higher production of
      IL-10 in spleen and also in the islets. This protective effect was also
      concomitant with the appearance of a regulatory cell population in the spleen and
      a decreased infiltration of the islets by T CD8+ lymphocytes. The vector (DNAv)
      also determined immunomodulation but its protective effect against insulitis was
      very discrete. CONCLUSION: The data presented in this study encourages a further
      investigation in the regulatory potential of the DNA-HSP65 construct. Our
      findings have important implications for the development of new immune therapy
      strategies to combat autoimmune diseases.

PMID- 19754944
TI  - The development of a knowledge test of depression and its treatment for patients
      suffering from non-psychotic depression: a psychometric assessment.
AB  - BACKGROUND: To develop and psychometrically assess a multiple choice question
      (MCQ) instrument to test knowledge of depression and its treatments in patients
      suffering from depression. METHODS: A total of 63 depressed patients and twelve
      psychiatric experts participated. Based on empirical evidence from an extensive
      review, theoretical knowledge and in consultations with experts, 27-item MCQ
      knowledge of depression and its treatment test was constructed. Data collected
      from the psychiatry experts were used to assess evidence of content validity for
      the instrument. RESULTS: Cronbach's alpha of the instrument was 0.68, and there
      was an overall 87.8% agreement (items are highly relevant) between experts about
      the relevance of the MCQs to test patient knowledge on depression and its
      treatments. There was an overall satisfactory patients' performance on the MCQs
      with 78.7% correct answers. Results of an item analysis indicated that most items
      had adequate difficulties and discriminations. CONCLUSION: There was adequate
      reliability and evidence for content and convergent validity for the instrument.
      Future research should employ a lager and more heterogeneous sample from both
      psychiatrist and community samples, than did the present study. Meanwhile, the
      present study has resulted in psychometrically tested instruments for measuring
      knowledge of depression and its treatment of depressed patients.

PMID- 19754945
TI  - Formal kinetics of H1N1 epidemic.
AB  - BACKGROUND: The formal kinetics of the H1N1 epidemic seems to take the form of an
      exponential curve. There is a good correlation between this theoretical model and
      epidemiological data on the number of H1N1-infected people. But this formal model
      leads to paradoxes about the dates when everyone becomes infected: in Mexico this
      will happen after one year, then in the rest of the world. FURTHER IMPLICATIONS
      OF THE FORMAL MODEL: The general limitations of this formal kinetics model are
      discussed. More detailed modeling is examined and the implications are examined
      in the light of currently available data. The evidence indicates that not more
      than 10% of the population is initially resistant to the H1N1 virus. CONCLUSION:
      We are probably only at the initial stage of development of the H1N1 epidemic.
      Increasing the number of H1N1-resistant people in future (e.g. due to
      vaccination) may influence the dynamics of epidemic development. At present, the
      development of the epidemic depends only on the number of people in the
      population who are initially resistant to the virus.

PMID- 19754946
TI  - Development of a fluorescent quantitative real-time polymerase chain reaction
      assay for the detection of Goose parvovirus in vivo.
AB  - BACKGROUND: Goose parvovirus (GPV) is a Dependovirus associated with latent
      infection and mortality in geese. Currently, it severely affects geese production
      worldwide. The objective of this study was to develop a fluorescent quantitative
      real-time polymerase chain reaction (PCR) (FQ-PCR) assay for fast and accurate
      quantification of GPV DNA in infected goslings, which can aid in the
      understanding of the regular distribution pattern and the nosogenesis of GPV in
      vivo. RESULTS: The detection limit of the assay was 2.8 x 10(1) standard DNA
      copies, with a sensitivity of 3 logs higher than that of the conventional gel
      based PCR assay targeting the same gene. The real-time PCR was reproducible, as
      shown by satisfactory low intraassay and interassay coefficients of variation.
      CONCLUSION: The high sensitivity, specificity, simplicity, and reproducibility of
      the GPV fluorogenic PCR assay, combined with a high throughput, make this method
      suitable for a broad spectrum of GPV etiology-related applications.

PMID- 19754947
TI  - Development of task switching and post-error-slowing in children.
AB  - BACKGROUND: Executive control processes such as task switching and error
      processing have been shown to change with age. The present study explored from a
      developmental perspective whether shared or different mechanisms underlie these
      processes. METHODS: The sample included 180 children (30 in each of the six age
      groups from 6-11 years) who were required to perform two different tasks:
      identification of a digit, or counting the number of digits. We computed switch
      costs as a function of response-repetition, stimulus-response (S-R)
      compatibility, and post-error-slowing. We also analyzed reaction time
      distributions. RESULTS AND DISCUSSION: The results showed a switch cost in the
      response-repetition condition, with a reduction in switch cost between 7 to 8 and
      9 to 10 years of age, and an S-R compatibility effect in 6 to 9 years old
      children. Reaction time (RT) distributions showed that the decrement in the
      switch cost is due to the overall decrease in RTs in fast (5th percentile) trials
      in 9 to 11 year olds, and slow (95th percentile) trials in 7 to 8 and 9 to 11
      years old children, in both the task switch and non-switch trials. A major
      reduction in RT was found between 9 to 11 years in both the response type and S-R
      compatibility type conditions. RT distributions for post-error trials revealed
      that the large decrement seen in 7 to 8 and 9 to 10 years old children is
      primarily due to the sudden decrease in RTs in the fast and slow trials
      respectively. The developmental pattern of error processing was similar to one
      component of task switching (switch cost of the response-repetition condition),
      indicating that inhibition could be a common mechanism underlying both the
      processes. However, the failure to maintain task set was found only with task
      switching. CONCLUSION: The development of task switching and error processing is
      not gradual. The developmental pattern of error processing is similar to that of
      the switch cost of the response-repetition condition in task switching,
      indicating that inhibition could be a common mechanism underlying both processes.
      The present results have implications for theories of executive control.

PMID- 19754948
TI  - Evaluation of nine candidate genes in patients with normal tension glaucoma: a
      case control study.
AB  - BACKGROUND: Normal tension glaucoma is a major subtype of glaucoma, associated
      with intraocular pressures that are within the statistically normal range of the
      population. Monogenic forms following classical inheritance patterns are rare in
      this glaucoma subtype. Instead, multigenic inheritance is proposed for the
      majority of cases. The present study tested common sequence variants in candidate
      genes for association with normal tension glaucoma in the German population.
      METHODS: Ninety-eight SNPs were selected to tag the common genetic variation in
      nine genes, namely OPTN (optineurin), RDX (radixin), SNX16 (sorting nexin 16),
      OPA1 (optic atrophy 1), MFN1 (mitofusin 1), MFN2 (mitofusin 2), PARL (presenilin
      associated, rhomboid-like), SOD2 (superoxide dismutase 2, mitochondrial) and
      CYP1B1 (cytochrome P450, family 1, subfamily B, polypeptide 1). These SNPs were
      genotyped in 285 cases and 282 fully evaluated matched controls. Statistical
      analyses comprised single polymorphism association as well as haplogroup based
      association testing. RESULTS: Results suggested that genetic variation in five of
      the candidate genes (RDX, SNX16, OPA1, SOD2 and CYP1B1) is unlikely to confer
      major risk to develop normal tension glaucoma in the German population. In
      contrast, we observed a trend towards association of single SNPs in OPTN, MFN1,
      MFN2 and PARL. The SNPs of OPTN, MFN2 and PARL were further analysed by
      multimarker haplotype-based association testing. We identified a risk haplotype
      being more frequent in patients and a vice versa situation for the complementary
      protective haplotype in each of the three genes. CONCLUSION: Common variants of
      OPTN, PARL, MFN1 and MFN2 should be analysed in other cohorts to confirm their
      involvement in normal tension glaucoma.

PMID- 19754949
TI  - Inferring speciation modes in a clade of Iberian chafers from rates of
      morphological evolution in different character systems.
AB  - BACKGROUND: Studies of speciation mode based on phylogenies usually test the
      predicted effect on diversification patterns or on geographical distribution of
      closely related species. Here we outline an approach to infer the prevalent
      speciation mode in Iberian Hymenoplia chafers through the comparison of the
      evolutionary rates of morphological character systems likely to be related to
      sexual or ecological selection. Assuming that mitochondrial evolution is neutral
      and not related to measured phenotypic differences among the species, we contrast
      hypothetic outcomes of three speciation modes: 1) geographic isolation with
      subsequent random morphological divergence, resulting in overall change
      proportional to the mtDNA rate; 2) sexual selection on size and shape of the male
      intromittent organs, resulting in an evolutionary rate decoupled to that of the
      mtDNA; and 3) ecological segregation, reflected in character systems presumably
      related to ecological or biological adaptations, with rates decoupled from that
      of the mtDNA. RESULTS: The evolutionary rate of qualitative external body
      characters was significantly correlated to that of the mtDNA both for the overall
      root-to-tip patristic distances and the individual inter-node branches, as
      measured with standard statistics and the randomization of a global comparison
      metric (the z-score). The rate of the body morphospace was significantly
      correlated to that of the mtDNA only for the individual branches, but not for the
      patristic distances, while that of the paramere outline was significantly
      correlated with mtDNA rates only for the patristic distances but not for the
      individual branches. CONCLUSION: Structural morphological characters, often used
      for species recognition, have evolved at a rate proportional to that of the
      mtDNA, with no evidence of directional or stabilising selection according to our
      measures. The change in body morphospace seems to have evolved randomly at short
      term, but the overall change is different from that expected under a pure random
      drift or randomly fluctuating selection, reflecting either directional or
      stabilising selection or developmental constraints. Short term changes in
      paramere shape possibly reflect sexual selection, but their overall amount of
      change was unconstrained, possibly reflecting their lack of functionality. Our
      approach may be useful to provide indirect insights into the prevalence of
      different speciation modes in entire lineages when direct evidence is lacking.

PMID- 19754950
TI  - Raising awareness of carrier testing for hereditary haemoglobinopathies in high
      risk ethnic groups in the Netherlands: a pilot study among the general public and
      primary care providers.
AB  - BACKGROUND: In the Netherlands no formal recommendations exist concerning
      preconceptional or antenatal testing for carriership of hereditary
      haemoglobinopathies. Those at highest risk may be unaware of the possibility of
      carrier screening. While universal newborn screening has recently been
      introduced, neither preconceptional nor antenatal carrier testing is routinely
      offered by health care services to the general public. A municipal health service
      and a foundation for public information on medical genetics undertook a pilot
      project with the aim of increasing knowledge and encouraging informed choice. Two
      groups were targeted: members of the public from ethnic groups at increased risk,
      and primary health care providers. This study examines the effectiveness of
      culturally specific 'infotainment' to inform high-risk ethnic groups about their
      increased risk for haemoglobinopathies. In addition, the study explores attitudes
      and intentions of primary care providers towards haemoglobinopathy carrier
      testing of their patients from high-risk ethnic groups. METHODS: Informational
      sessions tailored to the public or professionals were organised in Amsterdam, and
      evaluated for their effect. Psychological parameters were measured using
      structured questionnaires based on the Theory of Planned Behaviour. RESULTS: The
      pre-test/post-test questionnaire showed that members of the public gained
      understanding of inheritance and carriership of haemoglobinopathies from the
      "infotainment" session (p < 0.01). Perceived behavioural control, i.e. the
      feeling that they could actually get tested if they wanted to, increased in the
      targeted age group of 18-45 years (N = 41; p < 0.05). 191 surveys were collected
      from general practitioners or midwives. Their attitude towards the education
      programme for high-risk ethnic groups was positive, yet they did not show strong
      intention to effectuate carrier testing of their patients on the basis of
      ethnicity. The main factor which explained their (lack of) intention was social
      norm, i.e. their perception of negative peer opinion (41% variance explained).
      The majority of primary health care providers felt that policy change was
      unnecessary. CONCLUSION: The "infotainment" programme may have a positive effect
      on people from high-risk groups, but informed general practitioners and midwives
      were reluctant to facilitate their patients' getting tested. Additional
      initiatives are needed to motivate primary care providers to facilitate
      haemoglobinopathy carrier testing for their patients from high-risk backgrounds.

PMID- 19754951
TI  - New insights into molecular pathways associated with flatfish ovarian development
      and atresia revealed by transcriptional analysis.
AB  - BACKGROUND: The Senegalese sole (Solea senegalensis) is a marine flatfish of
      increasing commercial interest. However, the reproduction of this species in
      captivity is not yet controlled mainly because of the poor knowledge on its
      reproductive physiology, as it occurs for other non-salmonid marine teleosts that
      exhibit group-synchronous ovarian follicle development. In order to investigate
      intra-ovarian molecular mechanisms in Senegalese sole, the aim of the present
      study was to identify differentially expressed genes in the ovary during oocyte
      growth (vitellogenesis), maturation and ovarian follicle atresia using a recently
      developed oligonucleotide microarray. RESULTS: Microarray analysis led to the
      identification of 118 differentially expressed transcripts, of which 20 and 8
      were monitored by real-time PCR and in situ hybridization, respectively. During
      vitellogenesis, many up-regulated ovarian transcripts had putative mitochondrial
      function/location suggesting high energy production (NADH dehydrogenase subunits,
      cytochromes) and increased antioxidant protection (selenoprotein W2a), whereas
      other regulated transcripts were related to cytoskeleton and zona radiata
      organization (zona glycoprotein 3, alpha and beta actin, keratin 8),
      intracellular signalling pathways (heat shock protein 90, Ras homolog member G),
      cell-to-cell and cell-to-matrix interactions (beta 1 integrin, thrombospondin
      4b), and the maternal RNA pool (transducer of ERBB2 1a, neurexin 1a). Transcripts
      up-regulated in the ovary during oocyte maturation included ion transporters (Na+
      K+-ATPase subunits), probably required for oocyte hydration, as well as a
      proteinase inhibitor (alpha-2-macroglobulin) and a vesicle calcium sensor protein
      (extended synaptotagmin-2-A). During follicular atresia, few transcripts were
      found to be up-regulated, but remarkably most of them were localized in
      follicular cells of atretic follicles, and they had inferred roles in lipid
      transport (apolipoprotein C-I), chemotaxis (leukocyte cell-derived chemotaxin
      2,), angiogenesis (thrombospondin), and prevention of apoptosis (S100a10 calcium
      binding protein). CONCLUSION: This study has identified a number of
      differentially expressed genes in the ovary that were not previously found to be
      regulated during ovarian development in marine fish. Specifically, we found
      evidence, for the first time in teleosts, of the activation of chemoattractant,
      angiogenic and antiapoptotic pathways in hypertrophied follicular cells at the
      onset of ovarian atresia.

PMID- 19754952
TI  - 2D proteome analysis initiates new insights on the Salmonella Typhimurium LuxS
      protein.
AB  - BACKGROUND: Quorum sensing is a term describing a bacterial communication system
      mediated by the production and recognition of small signaling molecules. The LuxS
      enzyme, catalyzing the synthesis of AI-2, is conserved in a wide diversity of
      bacteria. AI-2 has therefore been suggested as an interspecies quorum sensing
      signal. To investigate the role of endogenous AI-2 in protein expression of the
      Gram-negative pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium),
      we performed a 2D-DIGE proteomics experiment comparing total protein extract of
      wildtype S. Typhimurium with that of a luxS mutant, unable to produce AI-2.
      RESULTS: Differential proteome analysis of wildtype S. Typhimurium versus a luxS
      mutant revealed relatively few changes beyond the known effect on phase 2
      flagellin. However, two highly differentially expressed protein spots with
      similar molecular weight but differing isoelectric point, were identified as LuxS
      whereas the S. Typhimurium genome contains only one luxS gene. This observation
      was further explored and we show that the S. Typhimurium LuxS protein can undergo
      posttranslational modification at a catalytic cysteine residue. Additionally, by
      constructing LuxS-betala and LuxS-PhoA fusion proteins, we demonstrate that S.
      Typhimurium LuxS can substitute the cognate signal peptide sequences of beta
      lactamase and alkaline phosphatase for translocation across the cytoplasmic
      membrane in S. Typhimurium. This was further confirmed by fractionation of S.
      Typhimurium protein extracts, followed by Western blot analysis. CONCLUSION: 2D
      DIGE analysis of a luxS mutant vs. wildtype Salmonella Typhimurium did not reveal
      new insights into the role of AI-2/LuxS in Salmonella as only a small amount of
      proteins were differentially expressed. However, subsequent in depth analysis of
      the LuxS protein itself revealed two interesting features: posttranslational
      modification and potential translocation across the cytoplasmic membrane. As the
      S. Typhimurium LuxS protein does not contain obvious signal motifs, it is
      speculated that LuxS is a new member of so called moonlighting proteins. These
      observations might have consequences in future studies on AI-2 quorum signaling
      in S. Typhimurium.

PMID- 19754953
TI  - Agreement between clinicians' and care givers' assessment of intelligence in
      Nigerian children with intellectual disability: 'ratio IQ' as a viable option in
      the absence of standardized 'deviance IQ' tests in sub-Saharan Africa.
AB  - BACKGROUND: There may be need to assess intelligent quotient (IQ) scores in sub
      Saharan African children with intellectual disability, either for the purpose of
      educational needs assessment or research. However, modern intelligence scales
      developed in the western parts of the world suffer limitation of widespread use
      because of the influence of socio-cultural variations across the world. This
      study examined the agreement between IQ scores estimation among Nigerian children
      with intellectual disability using clinicians' judgment based on International
      Classification of Diseases, tenth Edition(ICD - 10) criteria for mental
      retardation and caregivers judgment based on 'ratio IQ' scores calculated from
      estimated mental age in the context of socio-cultural milieu of the children. It
      proposed a viable option of IQ score assessment among sub-Saharan African
      children with intellectual disability, using a ratio of culture-specific
      estimated mental age and chronological age of the child in the absence of
      standardized alternatives, borne out of great diversity in socio-cultural context
      of sub-Saharan Africa. METHODS: Clinicians and care-givers independently assessed
      the children in relation to their socio-cultural background. Clinicians assessed
      the IQ scores of the children based on the ICD - 10 diagnostic criteria for
      mental retardation. 'Ratio IQ' scores were calculated from the ratio of estimated
      mental age and chronological age of each child. The IQ scores as assessed by the
      clinicians were then compared with the 'ratio IQ' scores using correlation
      statistics. RESULTS: A total of forty-four (44) children with intellectual
      disability were assessed. There was a significant correlation between clinicians'
      assessed IQ scores and the 'ratio IQ' scores employing zero order correlation
      without controlling for the chronological age of the children (r = 0.47, df = 42,
      p = 0.001). First order correlation controlling for the chronological age of the
      children showed higher correlation score between clinicians' assessed IQ scores
      and 'ratio IQ' scores (r = 0.75, df = 41, p = 0.000). CONCLUSION: Agreement
      between clinicians' assessed IQ scores and 'ratio IQ' scores was good. 'Ratio IQ'
      test would provide a viable option of assessing IQ scores in sub-Saharan African
      children with intellectual disability in the absence of culture-appropriate
      standardized intelligence scales, which is often the case because of great
      diversity in socio-cultural structures of sub-Saharan Africa.

PMID- 19754954
TI  - Inhibition of eIF2alpha dephosphorylation inhibits ErbB2-induced deregulation of
      mammary acinar morphogenesis.
AB  - BACKGROUND: The ErbB2/Her2/Neu receptor tyrosine kinase is amplified in
      approximately 30% of human breast cancers. Phosphorylation of the translation
      initiation factor, eIF2alpha inhibits global protein synthesis and activates a
      stress signaling and growth suppressive program. We have shown that forced
      phosphorylation of eIF2alpha can suppress head and neck, colorectal carcinoma and
      multiple myeloma tumor growth and/or survival. Here we explore whether ErbB2
      modulates eIF2alpha phosphorylation and whether forced phosphorylation of the
      latter can antagonize ErbB2 deregulation of mammary acinar morphogenesis.
      RESULTS: We tested whether ErbB2 signaling influenced eIF2alpha signaling and
      whether enhanced phosphorylation of the latter affected ErbB2-deregulated mammary
      acinar development. We obtained stable MCF10A cells overexpressing wild-type (Wt)
      Neu/ErbB2 or a constitutively active (CA) variant via retroviral delivery or
      mammary tumor cells from MMTV-Neu tumors. Western blotting, RT-PCR and confocal
      microscopy were used to analyze the effects of ErbB2 activation on eIF2alpha
      signaling and the effect of the GADD34-PP1C inhibitor salubrinal. Wt- and MMTV
      Neu cells formed aberrant acini structures resembling DCIS, while CA-ErbB2
      overexpression induced invasive lesions. In these structures we found that CA
      ErbB2 but not the Wt variant significantly down-regulated the pro-apoptotic gene
      CHOP. This occurred without apparent modulation of basal phosphorylation of PERK
      and eIF2alpha or induction of its downstream target ATF4. However, inhibition of
      eIF2alpha dephosphorylation with salubrinal was sufficient to inhibit Wt- and CA
      ErbB2- as well as MMTV-Neu-induced deregulation of acinar growth. This was linked
      to enhanced CHOP expression, inhibition of proliferation, induction of apoptosis
      and luminal clearing in Wt-ErbB2 and to inhibition of cyclin D1 levels and
      subsequent proliferation in CA-ErbB2 cells. CONCLUSION: Depending on the strength
      of ErbB2 signaling there is a differential regulation of CHOP and eIF2alpha
      phosphorylation. ErbB2 uncouples in basal conditions eIF2alpha phosphorylation
      from CHOP induction. However, this signal was restored by salubrinal treatment in
      Wt-ErbB2 expressing MCF10A cells as these DCIS-like structures underwent luminal
      clearing. In CA-ErbB2 structures apoptosis is not induced by salubrinal and
      instead a state of quiescence with reduced proliferation was achieved. Treatments
      that stabilize P-eIF2alpha levels may be effective in treating ErbB2 positive
      cancers without severely disrupting normal tissue function and structure.

PMID- 19754955
TI  - Use of the slide positivity rate to estimate changes in malaria incidence in a
      cohort of Ugandan children.
AB  - BACKGROUND: As malaria control efforts intensify, it is critical to monitor
      trends in disease burden and measure the impact of interventions. A key
      surveillance indicator is the incidence of malaria. Yet measurement of incidence
      is challenging. The slide positivity rate (SPR) has been used as a surrogate
      measure of malaria incidence, but limited data exist on the relationship between
      SPR and the incidence of malaria. METHODS: A cohort of 690 children aged 1-10
      years at enrollment were followed for all their health care needs over a four
      year period in Kampala, Uganda. All children with fever underwent laboratory
      testing, allowing us to measure the incidence of malaria and non-malaria fevers.
      A formula was derived to estimate relative changes in the incidence of malaria
      (rDeltaIm) based on changes in the SPR and the assumption that the incidence of
      non-malaria fevers was consistent over time. Observed and estimated values of
      rDeltaIm were compared over two, six, and 12 month time intervals after
      restricting the analysis to children contributing observation time between the
      ages of 4-10 years to control for aging of the cohort. RESULTS: Over the four
      year observation period the incidence of malaria declined significantly from 0.93
      episodes per person-year in 2005 to 0.39 episodes per person-year in 2008 (p <
      0.0001) and the incidence of non-malaria fevers declined significantly from 2.31
      episodes per person-year in 2005 to 1.31 episodes per person-year in 2008 (p <
      0.0001). Younger age was associated with a significantly greater incidence of
      malaria and the incidence of malaria was significantly higher during seasonal
      peaks occurring each January-February and May-June. Changes in SPR produced
      reasonably accurate estimates of rDeltaIm over all time intervals. The average
      absolute difference in observed and estimated values of rDeltaIm was lower for
      six-month intervals (0.13) than it was for two-month (0.21) or 12 month intervals
      (0.21). CONCLUSION: Changes in SPR provided a useful estimate of changes in the
      incidence of malaria in a well defined cohort; however, a gradual decline in the
      incidence of non-malaria fevers introduced some bias in these estimates.

PMID- 19754956
TI  - Assessing the genomic evidence for conserved transcribed pseudogenes under
      selection.
AB  - BACKGROUND: Transcribed pseudogenes are copies of protein-coding genes that have
      accumulated indicators of coding-sequence decay (such as frameshifts and
      premature stop codons), but nonetheless remain transcribed. Recent experimental
      evidence indicates that transcribed pseudogenes may regulate the expression of
      homologous genes, through antisense interference, or generation of small
      interfering RNAs (siRNAs). Here, we assessed the genomic evidence for such
      transcribed pseudogenes of potential functional importance, in the human genome.
      The most obvious indicators of such functional importance are significant
      evidence of conservation and selection pressure. RESULTS: A variety of pseudogene
      annotations from multiple sources were pooled and filtered to obtain a subset of
      sequences that have significant mid-sequence disablements (frameshifts and
      premature stop codons), and that have clear evidence of full-length mRNA
      transcription. We found 1750 such transcribed pseudogene annotations (TPAs) in
      the human genome (corresponding to approximately 11.5% of human pseudogene
      annotations). We checked for syntenic conservation of TPAs in other mammals
      (rhesus monkey, mouse, rat, dog and cow). About half of the human TPAs are
      conserved in rhesus monkey, but strikingly, very few in mouse (approximately 3%).
      The TPAs conserved in rhesus monkey show evidence of selection pressure (relative
      to surrounding intergenic DNA) on: (i) their GC content, and (ii) their rate of
      nucleotide substitution. This is in spite of distributions of Ka/Ks (ratios of
      non-synonymous to synonymous substitution rates), congruent with a lack of
      protein-coding ability. Furthermore, we have identified 68 human TPAs that are
      syntenically conserved in at least two other mammals. Interestingly, we observe
      three TPA sequences conserved in dog that have intermediate character (i.e.,
      evidence of both protein-coding ability and pseudogenicity), and discuss the
      implications of this. CONCLUSION: Through evolutionary analysis, we have
      identified candidate sequences for functional human transcribed pseudogenes, and
      have pinpointed 68 strong candidates for further investigation as potentially
      functional transcribed pseudogenes across multiple mammal species.

PMID- 19754957
TI  - Bridging the care continuum: patient information needs for specialist referrals.
AB  - BACKGROUND: Information transfer is critical in the primary care to specialist
      referral process and has been examined extensively in the US and other countries,
      yet there has been little attention to the patient's perspective of the
      information transfer process. This cross-sectional study examined the quality of
      the information received by patients with a chronic condition from the referring
      and specialist physician in the specialist referral process and the relationship
      of the quality of information received to trust in the physicians. METHODS:
      Structured telephone interviews were conducted with a random sample of 250
      patients who had experienced a referral to a specialist for the first visit for a
      chronic condition within the prior six months. The sample was selected from the
      patients who visited specialist physicians at any of the 500 hospitals from the
      National Research Corporation client base. RESULTS: Most patients (85%) received
      a good explanation about the reason for the specialist visit from the referring
      physician yet 26% felt unprepared about what to expect. Trust in the referring
      physician was highly associated with the preparatory information patients
      received. Specialists gave good explanations about diagnosis and treatment, but
      26% of patients got no information about follow-up. Trust in the specialist
      correlated highly with good explanations of diagnosis, treatment, and self
      management. CONCLUSION: Preparatory information from referring physicians
      influences the quality of the referral process, the subsequent coordination of
      care, and trust in the physician. Changes in the health care system can improve
      the information transfer process and improve coordination of care for patients.

PMID- 19754958
TI  - Interaction of ZEB and histone deacetylase with the PLDLS-binding cleft region of
      monomeric C-terminal binding protein 2.
AB  - BACKGROUND: Proteins of the C-terminal binding protein (CtBP) family, CtBP1 and
      CtBP2 are closely related transcriptional regulators that are coded by two
      different gene loci in the vertebrate genomes. They perform redundant and unique
      functions during animal development. CtBP proteins mediate their transcriptional
      function through interaction with various DNA-binding repressors that contain
      PLDLS-like motifs and chromatin modifying enzymes, such as class I histone
      deacetylases (HDAC) that do not contain such motifs. The N-terminal region of
      CtBP1/2 forms a hydrophobic cleft and is involved in interaction with both PLDLS
      containing factors and non-PLDLS factors. CtBP proteins function as dimers to
      mediate transcriptional repression and dimerization is modulated by specific
      binding to NAD/NADH. RESULTS: In this study, we have investigated the role of
      dimerization of CtBP2 in recruitment of PLDLS-motif cofactors and non-PLDLS
      cofactors. Our results indicate that mutations in CtBP2 that interfere with
      dimerization abolish CtBP2 interaction with most cellular factors, except the
      PLDLS-motif factor zinc-finger E-box binding homeobox (ZEB) and the non-PLDLS
      factor HDAC2. Unlike most PLDLS-containing CtBP-binding proteins, ZEB contains
      three PLDLS-like motifs and all three contribute to the interaction with the
      CtBP2 monomer. Despite the ability to interact with ZEB and HDAC, the CtBP2
      monomer fails to mediate ZEB-dependent transcriptional repression. The lack of
      repression activity of the CtBP2 monomer is correlated with the competition
      between ZEB and HDAC for interaction with the CtBP2 monomer. CONCLUSION: These
      results suggest a competition between the canonical PLDLS-motif factors such as
      E1A and non-PLDLS factor HDAC for interaction with CtBP. They also indicate that
      the affinity for the CtBP monomer may be determined by the number as well as
      amino acid sequence compositions of the PLDLS-like motifs. Our results are
      consistent with a model that the CtBP2 dimer may interact with a PLDLS-containing
      repressor through one monomer and recruit HDAC and other chromatin modifying
      enzymes through the second monomer in the CtBP2 dimer.

PMID- 19754959
TI  - Effectiveness of early detection on breast cancer mortality reduction in
      Catalonia (Spain).
AB  - BACKGROUND: At present, it is complicated to use screening trials to determine
      the optimal age intervals and periodicities of breast cancer early detection.
      Mathematical models are an alternative that has been widely used. The aim of this
      study was to estimate the effect of different breast cancer early detection
      strategies in Catalonia (Spain), in terms of breast cancer mortality reduction
      (MR) and years of life gained (YLG), using the stochastic models developed by Lee
      and Zelen (LZ). METHODS: We used the LZ model to estimate the cumulative
      probability of death for a cohort exposed to different screening strategies after
      T years of follow-up. We also obtained the cumulative probability of death for a
      cohort with no screening. These probabilities were used to estimate the possible
      breast cancer MR and YLG by age, period and cohort of birth. The inputs of the
      model were: incidence of, mortality from and survival after breast cancer,
      mortality from other causes, distribution of breast cancer stages at diagnosis
      and sensitivity of mammography. The outputs were relative breast cancer MR and
      YLG. RESULTS: Relative breast cancer MR varied from 20% for biennial exams in the
      50 to 69 age interval to 30% for annual exams in the 40 to 74 age interval. When
      strategies differ in periodicity but not in the age interval of exams, biennial
      screening achieved almost 80% of the annual screening MR. In contrast to MR, the
      effect on YLG of extending screening from 69 to 74 years of age was smaller than
      the effect of extending the screening from 50 to 45 or 40 years. CONCLUSION: In
      this study we have obtained a measure of the effect of breast cancer screening in
      terms of mortality and years of life gained. The Lee and Zelen mathematical
      models have been very useful for assessing the impact of different modalities of
      early detection on MR and YLG in Catalonia (Spain).

PMID- 19754960
TI  - Bridging the gap between systems biology and medicine.
AB  - Systems biology has matured considerably as a discipline over the last decade,
      yet some of the key challenges separating current research efforts in systems
      biology and clinically useful results are only now becoming apparent. As these
      gaps are better defined, the new discipline of systems medicine is emerging as a
      translational extension of systems biology. How is systems medicine defined? What
      are relevant ontologies for systems medicine? What are the key theoretic and
      methodologic challenges facing computational disease modeling? How are inaccurate
      and incomplete data, and uncertain biologic knowledge best synthesized in useful
      computational models? Does network analysis provide clinically useful insight? We
      discuss the outstanding difficulties in translating a rapidly growing body of
      data into knowledge usable at the bedside. Although core-specific challenges are
      best met by specialized groups, it appears fundamental that such efforts should
      be guided by a roadmap for systems medicine drafted by a coalition of scientists
      from the clinical, experimental, computational, and theoretic domains.

PMID- 19754961
TI  - Expression of cartilage-derived morphogenetic protein in human intervertebral
      discs and its effect on matrix synthesis in degenerate human nucleus pulposus
      cells.
AB  - INTRODUCTION: Loss of intervertebral disc (IVD) matrix and ultimately disc height
      as a result of 'degeneration' has been implicated as a major cause of low back
      pain (LBP). The use of anabolic growth factors as therapies to regenerate IVD
      matrix, hence restoring disc height and thus reversing degenerative disc disease,
      has been suggested. Cartilage-derived morphogenetic protein (CDMP) is a growth
      factor which stimulates proteoglycan production in chondrocyte-like cells and
      thus could be a useful growth factor for LBP therapies. However, little is known
      about the expression of CDMP or its receptor in human IVD, nor its effects on
      human disc cells. METHODS: Using immunohistochemistry we investigated the
      localisation of CDMP in non-degenerate and degenerate human IVDs. Additionally,
      we investigated the effect of CDMP on aggrecan and type II collagen gene
      expression and proteoglycan synthesis in nucleus pulposus (NP) cells derived from
      degenerate IVDs. RESULTS: We demonstrated that CDMP 1 and 2 were expressed in the
      non-degenerate and degenerate IVD, particularly in cells of the NP. A small
      decrease in the number of CDMP 1 and 2 immunopositive cells was seen with
      degeneration. Treatment of human NP cells, (derived from degenerate IVD), with
      CDMP showed an increase in aggrecan and type II collagen gene expression and
      increased production of proteoglycan (GAGs). CONCLUSIONS: The data suggests that
      CDMP may be a useful growth factor to stimulate proteoglycan production in the
      human degenerate IVD and hence the repair of the extracellular matrix.

PMID- 19754962
TI  - Advantages of the Ilizarov external fixation in the management of intra-articular
      fractures of the distal tibia.
AB  - BACKGROUND: Treatment of distal tibial intra-articular fractures is challenging
      due to the difficulties in achieving anatomical reduction of the articular
      surface and the instability which may occur due to ligamentous and soft tissue
      injury. The purpose of this study is to present an algorithm in the application
      of external fixation in the management of intra-articular fractures of the distal
      tibia either from axial compression or from torsional forces. MATERIALS AND
      METHODS: Thirty two patients with intra-articular fractures of the distal tibia
      have been studied. Based on the mechanism of injury they were divided into two
      groups. Group I includes 17 fractures due to axial compression and group II 15
      fractures due to torsional force. An Ilizarov external fixation was used in 15
      patients (11 of group I and 4 of group II). In 17 cases (6 of group I and 11 of
      group II) a unilateral hinged external fixator was used. In 7 out of 17 fractures
      of group I an additional fixation of the fibula was performed. RESULTS: All
      fractures were healed. The mean time of removal of the external fixator was 11
      weeks for group I and 10 weeks for group II. In group I, 5 patients had
      radiological osteoarthritic lesions (grade III and IV) but only 2 were
      symptomatic. Delayed union occurred in 3 patients of group I with fixed fibula.
      Other complications included one patient of group II with subluxation of the
      ankle joint after removal of the hinged external fixator, in 2 patients reduction
      found to be insufficient during the postoperative follow up and were revised and
      6 patients had a residual pain. The range of ankle joint motion was larger in
      group II. CONCLUSION: Intra-articular fractures of the distal tibia due to axial
      compression are usually complicated with cartilaginous problems and are requiring
      anatomical reduction of the articular surface. Fractures due to torsional forces
      are complicated with ankle instability and reduction should be augmented with
      ligament repair, in order to restore normal movement of talus against the
      mortise. Both Ilizarov and hinged external fixators are unable to restore
      ligamentous stability. External fixation is recommended only for fractures of the
      ankle joint caused by axial compression because it is biomechanically superior
      and has a lower complication rate.

PMID- 19754963
TI  - Preliminary investigation of a polyethylene glycol hydrogel "nerve glue".
AB  - BACKGROUND: Polyethylene glycol (PEG) hydrogel is a biocompatible semi-adherent
      gel like substance that can potentially augment nerve repair much like a fibrin
      sealant. Potential advantages of this substance include fast preparation and set
      up time, as well as adhesion inhibiting properties. The purpose of this study was
      to perform an initial evaluation of PEG hydrogel in this application. METHODS:
      The sciatic nerves of 29 rats were transected and repaired using two 10-0 nylon
      sutures and either PEG hydrogel or fibrin glue. After 10 weeks, contraction
      forces of the reinnervated muscles were evaluated and histological assessment of
      scar tissue performed. RESULTS: Muscle strength testing revealed the average
      ratio of experimental to control sides for the fibrin glue group was 0.75 and for
      the PEG hydrogel group was 0.72 (no significant difference). Longitudinal
      sections through the nerve repair site showed no significant difference in nerve
      diameter but did demonstrate a significant reduction in scar thickness in the PEG
      hydrogel group (p < 0.01). CONCLUSION: Though further study is necessary to fully
      evaluate, PEG hydrogel results in less scar tissue formation and equivalent
      muscle recovery as fibrin sealant when applied as a nerve glue in a rodent
      sciatic nerve repair model.

PMID- 19754964
TI  - Patient- and system-related barriers for the earlier diagnosis of colorectal
      cancer.
AB  - BACKGROUND: A cohort of colorectal cancer (CRC) patients represents an
      opportunity to study missed opportunities for earlier diagnosis. PRIMARY
      OBJECTIVE: To study the epidemiology of diagnostic delays and failures to
      offer/complete CRC screening. SECONDARY OBJECTIVE: To identify system- and
      patient-related factors that may contribute to diagnostic delays or failures to
      offer/complete CRC screening. METHODS:  SETTING: Rural Veterans Administration
      (VA) Healthcare system. PARTICIPANTS: CRC cases diagnosed within the VA between
      1/1/2000 and 3/1/2007. DATA SOURCES: progress notes, orders, and pathology,
      laboratory, and imaging results obtained between 1/1/1995 and 12/31/2007.
      Completed CRC screening was defined as a fecal occult blood test or flexible
      sigmoidoscopy (both within five years), or colonoscopy (within 10 years); delayed
      diagnosis was defined as a gap of more than six months between an abnormal test
      result and evidence of clinician response. A summary abstract of the antecedent
      clinical care for each patient was created by a certified gastroenterologist
      (GI), who jointly reviewed and coded the abstracts with a general internist (TW).
      RESULTS: The study population consisted of 150 CRC cases that met the inclusion
      criteria. The mean age was 69.04 (range 35-91); 99 (66%) were diagnosed due to
      symptoms; 61 cases (46%) had delays associated with system factors; of them, 57
      (38% of the total) had delayed responses to abnormal findings. Fifteen of the
      cases (10%) had prompt symptom evaluations but received no CRC screening; no
      patient factors were identified as potentially contributing to the failure to
      screen/offer to screen. In total, 97 (65%) of the cases had missed opportunities
      for early diagnosis and 57 (38%) had patient factors that likely contributed to
      the diagnostic delay or apparent failure to screen/offer to screen. CONCLUSION:
      Missed opportunities for earlier CRC diagnosis were frequent. Additional studies
      of clinical data management, focusing on following up abnormal findings, and
      offering/completing CRC screening, are needed.

PMID- 19754965
TI  - Maximising engagement, motivation and long term change in a Structured Intensive
      Education Programme in Diabetes for children, young people and their families:
      Child and Adolescent Structured Competencies Approach to Diabetes Education
      (CASCADE).
AB  - BACKGROUND: This trial aims to evaluate effective delivery and cost effectiveness
      of an innovative structured psycho-educational programme (CASCADE) for young
      people and their families living with diabetes. The increase in numbers of people
      being diagnosed with diabetes is posing a challenge for both the UK and the rest
      of the world. The peak age for diagnosis is between 10 and 14 years of age. There
      is clear evidence that improved diabetes control from diagnosis in childhood can
      reduce the incidence and progression of long-term complications. However, despite
      the development of improved insulin regimens and delivery methods, the overall
      metabolic control in children and adolescents has improved little in the UK in
      the past decade. Therefore there is a need for novel interventions and health
      delivery mechanisms aimed at young people and their families to help improve
      control and reduce complications, illness burden and costs to the NHS.
      METHODS/DESIGN: The CASCADE trial is a multi-centre randomised control trial with
      26 clinics randomised to control or intervention groups, with 572 children and
      young people involved in the study. The intervention will be delivered in 4 group
      sessions, over a 4 month period. A developmentally appropriate curriculum will be
      delivered to groups of 3 - 4 families, focusing on achievement of increasing
      competency in self-management of diabetes. The control group will receive
      standard care from their clinical team, usually consisting of regular 3-monthly
      clinic visits and telephone contact as required with the clinical nurse
      specialist and consultant. The primary outcomes of the trial will be change in
      HbA1c between baseline and 12 months and 24 months post recruitment. Secondary
      outcomes will include measures related to the economic evaluation, psychosocial
      outcomes, outcomes related to management of diabetes outcomes, and adherence to
      the intervention. DISCUSSION: The trial will be run by independent research and
      service delivery teams and supervised by a trial steering committee. A data
      monitoring and ethics committee has been put in place to monitor the trial and
      recommend stopping/continuation according to a Peto-Haybittle rule. The trial
      will be conducted according to the principles of MRC Good Clinical Practice (GCP)
      Guidelines and CTRU Phase III Trial Standard Operating procedures. TRIAL
      REGISTRATION: Current Controlled Trials ISRCTN52537669.

PMID- 19754966
TI  - An interdisciplinary team communication framework and its application to
      healthcare 'e-teams' systems design.
AB  - BACKGROUND: There are few studies that examine the processes that
      interdisciplinary teams engage in and how we can design health information
      systems (HIS) to support those team processes. This was an exploratory study with
      two purposes: (1) To develop a framework for interdisciplinary team communication
      based on structures, processes and outcomes that were identified as having
      occurred during weekly team meetings. (2) To use the framework to guide 'e-teams'
      HIS design to support interdisciplinary team meeting communication. METHODS: An
      ethnographic approach was used to collect data on two interdisciplinary teams.
      Qualitative content analysis was used to analyze the data according to
      structures, processes and outcomes. RESULTS: We present details for team meta
      concepts of structures, processes and outcomes and the concepts and sub concepts
      within each meta-concept. We also provide an exploratory framework for
      interdisciplinary team communication and describe how the framework can guide HIS
      design to support 'e-teams'. CONCLUSION: The structures, processes and outcomes
      that describe interdisciplinary teams are complex and often occur in a non-linear
      fashion. Electronic data support, process facilitation and team video
      conferencing are three HIS tools that can enhance team function.

PMID- 19754967
TI  - Complete absence of M2-pyruvate kinase expression in benign pancreatic ductal
      epithelium and pancreaticobiliary and duodenal neoplasia.
AB  - BACKGROUND: Elevated serum concentrations of M2-pyruvate kinase (M2-PK) correlate
      with poor prognosis in patients with pancreaticobiliary and duodenal cancer, but
      the expression of M2-PK in formalin-fixed pancreatic tissue is unknown. We aimed
      to characterise the immunohistochemical expression of M2-PK in archived specimens
      of pancreaticobiliary and duodenal cancers, premalignant lesions, chronic
      pancreatitis, and normal pancreas. METHODS: Immunohistochemical staining was
      performed with mouse anti-M2-PK monoclonal antibody (clone DF-4) at an optimal
      dilution of 1:25 on tissue microarrays constructed from formalin-fixed paraffin
      embedded pancreatic tissue of 126 consecutive patients undergoing pancreatic
      resections between June 2001 and June 2006. 104 underwent resection for cancer
      and 22 for chronic pancreatitis. 78 specimens of chronic pancreatitis tissue were
      obtained adjacent to areas of cancer. Normal pancreatic tissue was obtained from
      the resection specimens in a total of 30 patients. Metastatic tumours in 61
      regional lymph nodes from 61 patients were also studied. A further 11
      premalignant pancreaticobiliary and duodenal lesions were studied. M2-PK
      expression was quantified with the immunohistochemical score (IHS; Range 0-12).
      RESULTS: Benign non-ductal tissue in chronic pancreatitis and normal pancreas
      showed variable expression of M2-PK (IHS = 1 in 25%, IHS = 2-3 in 40%, IHS>3 in
      40%). Benign pancreatic ductal epithelium, all primary pancreaticobiliary and
      duodenal premalignant lesions and cancers (and lymph node metastasis) showed
      complete lack of expression (IHS = 0). CONCLUSION: Complete lack of M2-PK
      expression was observed in benign pancreatic ducts, premalignant lesions and
      cancer. M2-PK is present only in benign non-ductal epithelium in normal pancreas
      and peri-tumoural tissue.

PMID- 19754968
TI  - Identifying important motivational factors for professionals in Greek hospitals.
AB  - BACKGROUND: The purpose of this study was to identify important motivational
      factors according to the views of health-care professionals in Greek hospitals
      and particularly to determine if these might differ in the public and private
      sectors. METHODS: A previously developed -and validated- instrument addressing
      four work-related motivators (job attributes, remuneration, co-workers and
      achievements) was used. Three categories of health care professionals, doctors (N
      = 354), nurses (N = 581) and office workers (N = 418), working in public and
      private hospitals, participated and motivation was compared across socio
      demographic and occupational variables. RESULTS: The range of reported
      motivational factors was mixed and Maslow's conclusions that lower level
      motivational factors must be met before ascending to the next level were not
      confirmed. The highest ranked motivator for the entire sample, and by
      professional subgroup, was achievements (P < 0.001). Within subgroups, motivators
      were similar, and only one significant difference was observed, namely between
      doctors and nurses in respect to co-workers (P < 0.05). Remuneration (and salary
      in particular) was reported as a significant incentive only for professionals in
      managerial positions. Health professionals in private hospitals were motivated by
      all factors significantly more than their public-hospital counterparts.
      CONCLUSION: The results are in agreement with the literature which focuses
      attention to management approaches employing both monetary and non-monetary
      incentives to motivate health care workers. This study showed that intrinsic
      factors are particularly important and should become a target for effective
      employee motivation.

PMID- 19754969
TI  - Identifying research priorities for health care priority setting: a collaborative
      effort between managers and researchers.
AB  - BACKGROUND: To date there has been relatively little published about how research
      priorities are set, and even less about methods by which decision-makers can be
      engaged in defining a relevant and appropriate research agenda. We report on a
      recent effort in British Columbia to have researchers and decision-makers jointly
      establish an agenda for future research into questions of resource allocation.
      METHODS: The researchers enlisted decision-maker partners from each of British
      Columbia's six health authorities. Three forums were held, at which researchers
      and decision-makers from various levels in the health authorities considered
      possible research areas related to three key focus areas: (1) generation and use
      of decision criteria and measurement of 'benefit' against such criteria; (2)
      identification of so-called 'disinvestment' opportunities; and (3) evaluation of
      the effectiveness of priority setting procedures. Detailed notes were taken from
      each forum and synthesized into a set of qualitative themes. RESULTS: Forum
      participants suggested that future research into healthcare priority setting
      would benefit from studies that were longitudinal, comparative, and/or
      interdisciplinary. As well, participants identified two broad theme areas in
      which specific research projects were deemed desirable. First, future research
      might usefully consider how formal priority setting and resource allocation
      projects are situated within a larger organizational and political context.
      Second, additional research efforts should be devoted to better understanding and
      improving the actual implementation of priority setting frameworks, particularly
      with respect to issues of change management and the resolution of impediments to
      action on recommendations for resource allocation. CONCLUSION: We were able to
      validate the importance of initial areas posed to the group and observed
      emergence of additional concerns and directions of critical importance to these
      decision-makers at this time. It is likely that the results are broadly
      applicable to other healthcare contexts. The implementation of this research
      agenda in British Columbia will depend upon the ability of the researchers and
      decision-makers to develop particular projects that fit within the constraints of
      existing funding opportunities. The process of engagement itself had benefits in
      terms of connecting decision-makers with their peers and sparking increased
      interest in the use and refinement of priority setting frameworks.

PMID- 19754971
TI  - Acute liver failure due to concomitant arterial, portal and biliary injury during
      laparoscopic cholecystectomy: is transplantation a valid life-saving strategy? A
      case report.
AB  - BACKGROUND: Combined iatrogenic vascular and biliary injury during
      cholecystectomy resulting in ischemic hepatic necrosis is a very rare cause of
      acute liver failure. We describe a patient who developed fulminant liver failure
      as a result of severe cholestasis and liver gangrene secondary to iatrogenic
      combine injury or the hepatic pedicle (i.e. hepatic artery, portal vein and bile
      duct) during laparoscopic cholecystectomy. CASE PRESENTATION: A 40-years-old
      woman underwent laparoscopic cholecystectomy for acute cholecystitis. During
      laparoscopy, a severe bleeding at the liver hilum motivated the conversion to
      open surgery. Many sutures were placed across the parenchyma for bleeding
      control. After 48 hours, she rapidly deteriorated with encephalopathy,
      coagulopathy, persistent hypotension and progressive organ dysfunction including
      acute renal failure requiring hemodialysis and mechanical ventilation. An
      angiography documented an occlusion of right hepatic artery and right portal
      vein. In the clinical of acute liver failure secondary to liver gangrene, severe
      coagulopathy and progressive secondary multi-organ failure, the patient was
      included in the waiting list for liver transplantation. Two days later, the
      patient was successfully transplanted with initial adequate liver graft function.
      However, she developed bilateral pneumonia and severe gastrointestinal bleeding
      and finally died 24 days after transplantation due to bilateral necrotizing
      pneumonia. CONCLUSION: The occurrence of acute liver failure due to portal triad
      injury during laparoscopic cholecystectomy is a catastrophic complication.
      Probably, the indication of liver transplantation as a life-saving strategy in
      patients with late diagnosis, acute liver failure, severe coagulopathy and
      progressive secondary multi-organ failure could be considered but only minimizing
      immunosuppressive regimen to avoid postoperative infections.

PMID- 19754970
TI  - A systems biology framework for modeling metabolic enzyme inhibition of
      Mycobacterium tuberculosis.
AB  - BACKGROUND: Because metabolism is fundamental in sustaining microbial life, drugs
      that target pathogen-specific metabolic enzymes and pathways can be very
      effective. In particular, the metabolic challenges faced by intracellular
      pathogens, such as Mycobacterium tuberculosis, residing in the infected host
      provide novel opportunities for therapeutic intervention. RESULTS: We developed a
      mathematical framework to simulate the effects on the growth of a pathogen when
      enzymes in its metabolic pathways are inhibited. Combining detailed models of
      enzyme kinetics, a complete metabolic network description as modeled by flux
      balance analysis, and a dynamic cell population growth model, we quantitatively
      modeled and predicted the dose-response of the 3-nitropropionate inhibitor on the
      growth of M. tuberculosis in a medium whose carbon source was restricted to fatty
      acids, and that of the 5'-O-(N-salicylsulfamoyl) adenosine inhibitor in a medium
      with low-iron concentration. CONCLUSION: The predicted results quantitatively
      reproduced the experimentally measured dose-response curves, ranging over three
      orders of magnitude in inhibitor concentration. Thus, by allowing for detailed
      specifications of the underlying enzymatic kinetics, metabolic
      reactions/constraints, and growth media, our model captured the essential
      chemical and biological factors that determine the effects of drug inhibition on
      in vitro growth of M. tuberculosis cells.

PMID- 19754972
TI  - Phosphate decreases urine calcium and increases calcium balance: a meta-analysis
      of the osteoporosis acid-ash diet hypothesis.
AB  - BACKGROUND: The acid-ash hypothesis posits that increased excretion of "acidic"
      ions derived from the diet, such as phosphate, contributes to net acidic ion
      excretion, urine calcium excretion, demineralization of bone, and osteoporosis.
      The public is advised by various media to follow an alkaline diet to lower their
      acidic ion intakes. The objectives of this meta-analysis were to quantify the
      contribution of phosphate to bone loss in healthy adult subjects; specifically,
      a) to assess the effect of supplemental dietary phosphate on urine calcium,
      calcium balance, and markers of bone metabolism; and to assess whether these
      affects are altered by the b) level of calcium intake, c) the degree of
      protonation of the phosphate. METHODS: Literature was identified through
      computerized searches regarding phosphate with surrogate and/or direct markers of
      bone health, and was assessed for methodological quality. Multiple linear
      regression analyses, weighted for sample size, were used to combine the study
      results. Tests of interaction included stratification by calcium intake and
      degree of protonation of the phosphate supplement. RESULTS: Twelve studies
      including 30 intervention arms manipulated 269 subjects' phosphate intakes. Three
      studies reported net acid excretion. All of the meta-analyses demonstrated
      significant decreases in urine calcium excretion in response to phosphate
      supplements whether the calcium intake was high or low, regardless of the degree
      of protonation of the phosphate supplement. None of the meta-analyses revealed
      lower calcium balance in response to increased phosphate intakes, whether the
      calcium intake was high or low, or the composition of the phosphate supplement.
      CONCLUSION: All of the findings from this meta-analysis were contrary to the acid
      ash hypothesis. Higher phosphate intakes were associated with decreased urine
      calcium and increased calcium retention. This meta-analysis did not find evidence
      that phosphate intake contributes to demineralization of bone or to bone calcium
      excretion in the urine. Dietary advice that dairy products, meats, and grains are
      detrimental to bone health due to "acidic" phosphate content needs reassessment.
      There is no evidence that higher phosphate intakes are detrimental to bone
      health.

PMID- 19754973
TI  - Impact of sex, MHC, and age of recipients on the therapeutic effect of
      transferred leukocytes from cancer-resistant SR/CR mice.
AB  - BACKGROUND: Spontaneous Regression/Complete Resistant (SR/CR) mice are resistant
      to cancer through a mechanism that is mediated entirely by leukocytes of innate
      immunity. Transfer of leukocytes from SR/CR mice can confer cancer resistance in
      wild-type (WT) recipients in both preventative and therapeutic settings. In the
      current studies, we investigated factors that may impact the efficacy and
      functionality of SR/CR donor leukocytes in recipients. RESULTS: In sex-mismatched
      transfers, functionality of female donor leukocytes was not affected in male
      recipients. In contrast, male donor leukocytes were greatly affected in the
      female recipients. In MHC-mismatches, recipients of different MHC backgrounds, or
      mice of different strains, showed a greater negative impact on donor leukocytes
      than sex-mismatches. The negative effects of sex-mismatch and MHC-mismatch on
      donor leukocytes were additive. Old donor leukocytes performed worse than young
      donor leukocytes in all settings including in young recipients. Young recipients
      were not able to revive the declining function of old donor leukocytes. However,
      the function of young donor leukocytes declined gradually in old recipients,
      suggesting that an aged environment may contain factors that are deleterious to
      cellular functions. The irradiation of donor leukocytes prior to transfers had a
      profound suppressive effect on donor leukocyte functions, possibly as a result of
      impaired transcription. The cryopreserving of donor leukocytes in liquid nitrogen
      had no apparent effect on donor leukocyte functions, except for a small loss of
      cell number after revival from freezing. CONCLUSION: Despite the functional
      suppression of donor leukocytes in sex- and MHC-mismatched recipients, as well as
      old recipients, there was a therapeutic time period during the initial few weeks
      during which donor leukocytes were functional before their eventual rejection or
      functional decline. The eventual rejection of donor leukocytes will likely
      prevent donor leukocyte engraftment which would help minimize the risk of
      transfusion-associated graft-versus-host disease. Therefore, using leukocytes
      from healthy donors with high anti-cancer activity may be a feasible therapeutic
      concept for treating malignant diseases.

PMID- 19754974
TI  - Surface display of heterologous proteins in Bacillus thuringiensis using a
      peptidoglycan hydrolase anchor.
AB  - BACKGROUND: Previous studies have revealed that the lysin motif (LysM) domains of
      bacterial cell wall-degrading enzymes are able to bind to peptidoglycan moieties
      of the cell wall. This suggests an approach for a cell surface display system in
      Gram-positive bacteria using a LysM-containing protein as the anchoring motif. In
      this study, we developed a new surface display system in B. thuringiensis using a
      LysM-containing peptidoglycan hydrolase, endo-beta-N-acetylglucosaminidase (Mbg),
      as the anchor protein. RESULTS: Homology searching in the B. thuringiensis YBT
      1520 genome revealed a putative peptidoglycan hydrolase gene. The encoded
      protein, Mbg, exhibited substantial cell-wall binding capacity. The deduced amino
      acid sequence of Mbg was structurally distinguished as an N-terminal domain with
      two tandemly aligned LysMs and a C-terminal catalytic domain. A GFP-fusion
      protein was expressed and used to verify the surface localization by Western
      blot, flow cytometry, protease accessibility, SDS sensitivity,
      immunofluorescence, and electron microscopy assays. Low-level constitutive
      expression of Mbg was elevated by introducing a sporulation-independent promoter
      of cry3Aa. Truncated Mbg domains with separate N-terminus (Mbgn), C-terminus
      (Mbgc), LysM1, or LysM2 were further compared for their cell-wall displaying
      efficiencies. The Mbgn moiety contributed to cell-wall anchoring, while LysM1 was
      the active domain. Two tandemly repeated Mbgns exhibited the highest display
      activity, while the activity of three repeated Mbgns was decreased. A
      heterologous bacterial multicopper oxidase (WlacD) was successfully displayed
      onto the surface of B. thuringiensis target cells using the optimum (Mbgn)2
      anchor, without radically altering its catalytic activity. CONCLUSION: Mbg can be
      a functional anchor protein to target different heterologous proteins onto the
      surface of B. thuringiensis cells. Since the LysM domain appears to be universal
      in Gram-positive bacteria, the strategy presented here could be applicable in
      other bacteria for developing this type of system.

PMID- 19754975
TI  - Comparative analysis of complete nucleotide sequence of porcine reproductive and
      respiratory syndrome virus (PRRSV) isolates in Thailand (US and EU genotypes).
AB  - BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) is a
      causative agent of Porcine Reproductive and Respiratory Syndrome (PRRS). In this
      study, the complete nucleotide sequences of the selected two Thai PRRSV isolates,
      EU (01CB1) and US (01NP1) genotypes were determined since both isolates are the
      Thai prototypes. RESULTS: 01CB1 and 01NP1 contain 14,943 and 15,412 nucleotides,
      respectively. The viruses compose 2 untranslated regions (5' UTR and 3' UTR) and
      8 open reading frames (ORFs) designated as ORF1a, ORF1b and ORF2-7. Phylogenetic
      analysis of full length of the viruses also showed that the 01CB1 and 01NP1 were
      grouped into the EU and US genotype, respectively. In order to determine the
      genetic variation and genetic relatedness among PRRSV isolates, the complete
      nucleotide sequences of PRRSV isolated in Thailand, 01CB1 and 01NP1 were compared
      with those of 2 EU strains (Lelystad, and EuroPRRSV), 6 US strains (MLV, VR2332,
      PA8, 16244B, SP and HUN4). Our results showed that the 01CB1 genome shares
      approximately 99.2% (Lelystad) and 95.2% (EuroPRRSV) nucleotide identity with EU
      field strains. While, the 01NP1 genome has 99.9% nucleotide identity with a live
      vaccine strain (MLV) and 99.5% and 98.5% nucleotide identity with 2 other US
      isolates, VR2332 and 16244B, respectively. In addition, ORF5 nucleotide sequences
      of 9 PRRS viruses recovered in Thailand during 2002-2008 were also included in
      this study. Phylogenetic analysis of ORF5 showed high similarity among EU and US
      genotypes of the recent Thai PRRS viruses (2007-2008 viruses) with 01CB1 and
      01NP1. CONCLUSION: Overall, the results suggested that the Thai EU isolate
      (01CB1) may evolve from the EU prototype, Lelystad virus, whereas the Thai US
      isolate (01NP1) may originate and evolve from the vaccine virus or its
      derivatives. Interestingly, the US-MLV vaccine was not available in the Thai
      market in 2001. The Vaccine-like virus might have persisted in the imported pigs
      or semen and later spread in the Thai swine industry. This report is the first
      report of complete nucleotide sequences of the Thai PRRS viruses both EU and US
      genotypes.

PMID- 19754976
TI  - In Silico screening for functional candidates amongst hypothetical proteins.
AB  - BACKGROUND: The definition of a hypothetical protein is a protein that is
      predicted to be expressed from an open reading frame, but for which there is no
      experimental evidence of translation. Hypothetical proteins constitute a
      substantial fraction of proteomes of human as well as of other eukaryotes. With
      the general belief that the majority of hypothetical proteins are the product of
      pseudogenes, it is essential to have a tool with the ability of pinpointing the
      minority of hypothetical proteins with a high probability of being expressed.
      RESULTS: Here, we present an in silico selection strategy where eukaryotic
      hypothetical proteins are sorted according to two criteria that can be reliably
      identified in silico: the presence of subcellular targeting signals and presence
      of characterized protein domains. To validate the selection strategy we applied
      it on a database of human hypothetical proteins dating to 2006 and compared the
      proteins predicted to be expressed by our selecting strategy, with their status
      in 2008. For the comparison we focused on mitochondrial proteins, since
      considerable amounts of research have focused on this field in between 2006 and
      2008. Therefore, many proteins, defined as hypothetical in 2006, have later been
      characterized as mitochondrial. CONCLUSION: Among the total amount of human
      proteins hypothetical in 2006, 21% have later been experimentally characterized
      and 6% of those have been shown to have a role in a mitochondrial context. In
      contrast, among the selected hypothetical proteins from the 2006 dataset,
      predicted by our strategy to have a mitochondrial role, 53-62% have later been
      experimentally characterized, and 85% of these have actually been assigned a role
      in mitochondria by 2008.Therefore our in silico selection strategy can be used to
      select the most promising candidates for subsequent in vitro and in vivo
      analyses.

PMID- 19754977
TI  - The emerging role of autophagy in Parkinson's disease.
AB  - Parkinson's disease (PD) is the most common neurodegenerative movement disorder
      that affects about 1% of the population worldwide. Despite significant advances
      in the identification of genetic mutations and signaling pathways that are
      associated with the disease, the precise mechanisms implicated in the
      pathophysiology of the disease are not well understood. More importantly,
      treatments that are effective in reversing the progression of the disease is
      essentially lacking. Further investigation into the pathogenic mechanisms of PD
      thus presents a pressing concern for neuroscientists. Recently, deregulation of
      the autophagic pathway is observed in the brains of PD patients and in models of
      PD. In this review we summarize current literature on the emerging involvement of
      autophagy in PD, and the implication for future development of treatment against
      the disorder.

PMID- 19754978
TI  - A profile of the online dissemination of national influenza surveillance data.
AB  - BACKGROUND: Influenza surveillance systems provide important and timely
      information to health service providers on trends in the circulation of influenza
      virus and other upper respiratory tract infections. Online dissemination of
      surveillance data is useful for risk communication to health care professionals,
      the media and the general public. We reviewed national influenza surveillance
      websites from around the world to describe the main features of surveillance data
      dissemination. METHODS: We searched for national influenza surveillance websites
      for every country and reviewed the resulting sites where available during the
      period from November 2008 through February 2009. Literature about influenza
      surveillance was searched at MEDLINE for relevant hyperlinks to related websites.
      Non-English websites were translated into English using human translators or
      Google language tools. RESULTS: A total of 70 national influenza surveillance
      websites were identified. The percentage of developing countries with
      surveillance websites was lower than that of developed countries (22% versus 57%
      respectively). Most of the websites (74%) were in English or provided an English
      version. The most common surveillance methods included influenza-like illness
      consultation rates in primary care settings (89%) and laboratory surveillance
      (44%). Most websites (70%) provided data within a static report format and 66% of
      the websites provided data with at least weekly resolution. CONCLUSION:
      Appropriate dissemination of surveillance data is important to maximize the
      utility of collected data. There may be room for improvement in the style and
      content of the dissemination of influenza data to health care professionals and
      the general public.

PMID- 19754979
TI  - An innovative triple immunogold labeling method to investigate the hemopoietic
      stem cell niche in situ.
AB  - The ultrastructural study of rare cells within their niche in situ is very
      difficult. We have developed a method for locating individual transplanted cells
      and simultaneously identifying and analyzing the molecules and cellular
      phenotypes surrounding them in situ using transmission electron microscopy. This
      innovative method involves triple immunogold labeling combined with serial
      ultrathin sectioning. We demonstrate the validity of this approach by examining
      the niche of individual transplanted cells from a population highly enriched for
      hemopoietic stem cells and the ultrastructural expression of two key stem cell
      regulatory molecules, hyaluronic acid and osteopontin. In addition, we describe
      the phenotypes of the surrounding cells.

PMID- 19754980
TI  - Characterizing the two- and three-dimensional resolution of an improved
      aberration-corrected STEM.
AB  - The successful development of third-order aberration correctors in transmission
      electron microscopy has seen aberration-corrected electron microscopes evolve
      from specialist projects, custom built at a small number of sites to common
      instruments in many modern laboratories. Here we describe some initial results
      illustrating the two- and three-dimensional (3D) performance of an aberration
      corrected scanning transmission electron microscope with a prototype improved
      aberration corrector designed to also minimize fifth-order aberrations and a new,
      higher brightness gun. We show that atomic columns separated by 0.63 A can be
      resolved and demonstrate detection of single dopant atoms with 3D sensitivity.

PMID- 19754981
TI  - Spectrum simulation in DTSA-II.
AB  - Spectrum simulation is a useful practical and pedagogical tool. Particularly with
      complex samples or trace constituents, a simulation can help to understand the
      limits of the technique and the instrument parameters for the optimal
      measurement. DTSA-II, software for electron probe microanalysis, provides both
      easy to use and flexible tools for simulating common and less common sample
      geometries and materials. Analytical models based on (rhoz) curves provide quick
      simulations of simple samples. Monte Carlo models based on electron and X-ray
      transport provide more sophisticated models of arbitrarily complex samples. DTSA
      II provides a broad range of simulation tools in a framework with many different
      interchangeable physical models. In addition, DTSA-II provides tools for
      visualizing, comparing, manipulating, and quantifying simulated and measured
      spectra.

PMID- 19754982
TI  - A screening program for dancers administered by dancers.
AB  - Students enrolled in a dance kinesiology class were trained to administer a
      screening protocol on younger dancers in the same department. The dance
      kinesiology students gained experience assessing alignment and functional
      symmetry in their peers, and then recommended exercises for gaining awareness and
      developing balanced patterns of movement. This "low stakes" assessment created
      both dialogue and peer support centered on helping the screened dancers
      understand and effectively work with their individual capacities and limitations.
      The project was designed to contribute to a culture of wellness and education
      within the dance department.

PMID- 19754983
TI  - Moving beyond the neutral spine: stabilizing the dancer with lumbar extension
      dysfunction.
AB  - Dancers commonly suffer from low back pain. This is often associated with the
      extreme lumbar extension range of motion and prolonged lordotic postures required
      by some dance forms. There is ample literature documenting extension-related
      instabilities such as spondylolisthesis in dancers. The aim of this article is to
      review the changes in motor control that occur in patients with subtle clinical
      instability and recurrent low back pain. Recent studies have consistently
      demonstrated changes in neuromuscular function in patients with back pain, and
      spinal stability retraining has become a popular component of treatment. However,
      most research to date has focused on maintenance of neutral spinal postures
      during assessment and treatment, whereas dancers must be trained to move with
      control through full lumbar extension range of motion.

PMID- 19754984
TI  - Risk factors for lower back injury in male dancers performing ballet lifts.
AB  - Lower back injuries are common in ballet dancers. Allegedly there is a higher
      incidence in males than in females due to their lifting requirements. This study
      analyzes the estimated forces generated at the L5/S1 joint in five professional
      and three pre-professional male dancers performing full press (FP) and arabesque
      (AR) ballet lifts. The estimated peak lumbar anterior shear force (PLASF) was
      identified using a 3D motion analysis system, and was found to occur at the
      beginning of each lift, approximately 0.01 seconds prior to the ballerina moving
      vertically into the lift. Data representing the male dancers' posture at the
      point of PLASF were input into a 3D Static Strength Prediction Program (3DSSPP,
      University of Michigan, Centre for Ergonomics, 2006) to calculate the PLASF and
      corresponding compression forces. The compression forces identified in this way
      were found to be greater than the National Institute of Occupational Safety and
      Health, Back Compression Design Limit (3400N). This suggests that administrative
      controls such as monitoring the number of lifts performed daily are required to
      reduce the risk of lower back injury in male dancers. Comparison of the two lifts
      found significantly (p < 0.05) higher compression forces in the FP versus the AR
      lift. This could be attributed to a significantly (p < 0.05) larger horizontal
      distance between the male dancer and the ballerina, or the eccentric loading of
      the male dancers' lower limb and trunk musculature in the preparation phase of
      the FP. Retrospective regression analysis indicated that peak trunk extension
      velocity and the horizontal distance between the male dancer and the ballerina
      were significant (p < 0.05) predictors of PLASF.

PMID- 19754985
TI  - When can I start pointe work? Guidelines for initiating pointe training.
AB  - The initiation of pointe training for dance students should be determined after
      careful evaluation of a number of factors. These include: the dance student's
      stage of physical development; the quality of her (or his) trunk, abdominal and
      pelvic control ("core" stability); the alignment of her legs (hip-knee-ankle
      foot); the strength and flexibility of her feet and ankles; and the duration and
      frequency of her dance training. For students who meet the requirements related
      to all of these factors, began ballet training at age eight or later, and who are
      taking ballet class at least twice per week, pointe work should be initiated in
      the fourth year of training. Students with poor core stability or hypermobility
      of the feet and ankles may require additional strengthening to allow them to
      safely begin pointe training. For those who are only taking ballet classes once
      per week, or who are not truly pre-professional, pointe training should be
      discouraged. No student with insufficient ankle and foot plantar flexion range of
      motion or with poor lower extremity alignment should be allowed to do pointe
      work.

PMID- 19754986
TI  - Trauma to the knee in a young professional dancer.

PMID- 19754987
TI  - The promise of comprehensive cancer control.

PMID- 19754988
TI  - The past, present, and future of comprehensive cancer control from the state and
      tribal perspective.

PMID- 19754989
TI  - Attitudes on aging well among older African Americans and whites in South
      Carolina.
AB  - INTRODUCTION: Cognitive impairment in older adults is a major cause of functional
      disability. Interest in protecting brain health is likely to grow as the US
      population ages and more people have experiences with cognitive decline. Recent
      scientific evidence suggests that physical activity, heart-healthy diets, and
      social involvement may help to maintain brain health. We investigated attitudes
      about aging well among older African Americans and whites to inform the
      development of interventions to promote cognitive health. METHODS: We used a
      purposive sample to conduct 5 focus groups with African Americans (n = 42) and 4
      with whites (n = 41). Participants also completed a brief survey. In discussions
      centered on brain health, participants were asked to describe someone they know
      who is aging well. We used a grounded theory approach to guide the analysis and
      interpretation of the data. RESULTS: Both African Americans and whites said that
      components of aging well include social activity, a strong spiritual life, not
      taking medications, and traveling. African Americans said aging well means being
      cognitively intact, free of serious mobility impairment or other health problems,
      and independent. Whites described aging well as living a long time, staying
      physically active, maintaining a positive outlook, and having good genes.
      CONCLUSION: African Americans did not commonly associate physical activity with
      aging well, which suggests that tailored intervention strategies for promoting
      brain health should emphasize physical activity. African Americans and whites did
      not commonly associate nutrition with aging well, which also suggests a useful
      focus for public health interventions.

PMID- 19754990
TI  - Control of risk factors among people with diagnosed diabetes, by lower extremity
      disease status.
AB  - INTRODUCTION: We examined the control of modifiable risk factors among a national
      sample of diabetic people with and without lower extremity disease (LED).
      METHODS: The sample from the 1999-2004 National Health and Nutrition Examination
      Survey consisted of 948 adults aged 40 years or older with diagnosed diabetes and
      who had been assessed for LED. LED was defined as peripheral arterial disease
      (ankle-brachial index <0.9), peripheral neuropathy (> or = 1 insensate area), or
      presence of foot ulcer. Good control of modifiable risk factors, based on
      American Diabetes Association recommendations, included being a nonsmoker and
      having the following measurements: hemoglobin A1c (HbA1c) less than 7%, systolic
      blood pressure less than or equal to 130 mm Hg, diastolic blood pressure less
      than or equal to 80 mm Hg, high-density lipoprotein (HDL) cholesterol greater
      than 50 mg/dL, and body mass index (BMI) between 18.5 kg/m(2) and 24.9 kg/m(2).
      RESULTS: Diabetic people with LED were less likely than were people without LED
      to have recommended levels of HbA1c (39.3% vs 53.5%) and HDL cholesterol (29.7%
      vs 41.1%), but there were no differences in systolic or diastolic blood pressure,
      BMI classification, or smoking status between people with and without LED.
      Control of some risk factors differed among population subgroups. Notably, among
      diabetic people with LED, non-Hispanic blacks were more likely to have improper
      control of HbA1c (adjusted odds ratio [AOR] = 2.0; 95% confidence interval [CI],
      1.1-3.9), systolic blood pressure (AOR = 1.9; 95% CI, 1.1-3.2), and diastolic
      blood pressure (AOR = 2.6; 95% CI, 1.1-5.8), compared with non-Hispanic whites.
      CONCLUSION: Control of 2 of 6 modifiable risk factors was worse in diabetic
      adults with LED compared with diabetic adults without LED. Among diabetic people
      with LED, non-Hispanic blacks had worse control of 3 of 6 risk factors compared
      with non-Hispanic whites.

PMID- 19754991
TI  - Disparities in chronic disease among Canada's low-income populations.
AB  - INTRODUCTION: Many studies have found inequities in health among income groups in
      Canada. We report the variations in the major chronic disease risks among low
      income populations, by province of residence, as a proxy measure of social
      environment. METHODS: We used estimates from the 2005 Canadian Community Health
      Survey to study residents who were aged 45 years or older and from the lowest
      income quintile nationally. Multivariate logistic regression was used to examine
      the relationship between province of residence and risk of chronic diseases.
      RESULTS: British Columbia is the healthiest province overall but not in terms of
      its low-income residents, whereas Quebec's low-income residents are at the least
      risk for major chronic diseases. The significant differences in risk of
      hypertension, diabetes, and heart disease in favor of British Columbia over
      Quebec for the entire population disappear when considering only the low-income
      subset. CONCLUSION: Quebec's antipoverty strategy, formalized as law in 2002, has
      led to social and health care policies that appear to give its low-income
      residents advantages in chronic disease prevention. Our findings demonstrate that
      chronic disease prevalence is associated with investment in social supports to
      vulnerable populations.

PMID- 19754992
TI  - Disparities in cancer clinical trials: an analysis of comprehensive cancer
      control plans.
AB  - INTRODUCTION: Disparities in enrollment of adults in cancer clinical trials are
      well documented, but little is known about the attention given to this topic in
      comprehensive cancer control (CCC) plans. We assessed the extent to which CCC
      plans address disparities in clinical trials and whether jurisdictions whose
      plans address disparities also mandate third-party reimbursement for clinical
      trial participation. METHODS: We analyzed 57 CCC plans identified from Cancer
      PLANET (Plan, Link, Act, Network with Evidence-based Tools) and Cancerplan.org
      from April through December 2007. We searched plans for general and disparity
      specific content regarding clinical trials and analyzed the content for emergent
      themes. We assessed frequencies of themes, patterns between themes, and patterns
      between themes and laws. We reviewed third-party reimbursement laws, as of
      September 2007, as recorded by the National Cancer Institute's State Cancer
      Legislative Database. RESULTS: Fifty-five (96%) CCC plans had content regarding
      clinical trials. Of the 39 (71%) plans that specifically addressed disparities,
      13 (33%) were in a state with laws mandating third-party reimbursement.
      Increasing participation and education, awareness, and outreach were the most
      common themes identified. CONCLUSION: Although many CCC plans address disparities
      in clinical trials, few of those plans are in jurisdictions that have third-party
      reimbursement laws.

PMID- 19754993
TI  - School lunch source and adolescent dietary behavior.
AB  - INTRODUCTION: As rates of childhood obesity rise, the nutritional content of
      lunches eaten at school is more heavily scrutinized. We examined the association
      between dietary behaviors and the number of days that adolescents bring lunch to
      school. METHODS: We analyzed cross-sectional data for 2,774 adolescents who
      responded to the 2005 California Health Interview Survey and reported dietary
      behaviors for a weekday. RESULTS: In bivariate analyses, adolescents who
      typically brought their lunch from home 5 days per week ate fast food on fewer
      occasions; consumed fewer servings of soda, fried potatoes, and high-sugar foods;
      and ate more fruit and vegetables compared with adolescents who never brought
      their lunch to school. In linear regressions controlling for demographics, body
      mass index, desire to change weight, parent education, and adult presence after
      school, students who typically brought their lunch to school 5 days per week ate
      fast food 0.35 fewer times and consumed 0.35 fewer servings of soda, 0.10 fewer
      servings of fried potatoes, 0.25 fewer servings of high-sugar foods, and 0.95
      more servings of fruit and vegetables per day compared with students who never
      brought their lunch to school. CONCLUSION: These findings suggest that
      adolescents who bring lunch to school from home have more positive dietary
      behaviors than do adolescents who get their lunches from other sources. Improving
      the nutritional quality of foods offered from other sources, such as the National
      School Lunch Program and competitive foods, could help improve adolescent dietary
      behaviors.

PMID- 19754994
TI  - Calories from beverages purchased at 2 major coffee chains in New York City,
      2007.
AB  - INTRODUCTION: Calorie intake from beverages has increased in the past decades,
      which most likely contributes to higher obesity rates. Although coffee chains
      have grown in popularity in recent years, few data examine the calorie
      contribution of these drinks. We examined afternoon beverage purchases in New
      York City at 2 major coffee chains and estimated the mean calorie content of
      these beverages. METHODS: We collected purchase receipts and brief surveys from
      adult customers at 42 Starbucks and 73 Dunkin' Donuts stores during the spring of
      2007. For each purchase, we obtained the calorie content from the company's Web
      site; these values were adjusted to account for self-reported customization of
      the drink. RESULTS: We included 1,127 beverage purchases at Starbucks and 1,830
      at Dunkin' Donuts in our analyses. Brewed coffee or tea averaged 63 kcal, and
      blended coffee beverages averaged 239 kcal. Approximately two-thirds of purchases
      at Starbucks and one-fourth of purchases at Dunkin' Donuts were blended coffee
      beverages. CONCLUSION: Calories in blended coffee beverages are high; on average,
      customers bought 12% of a 2,000-kcal diet. Policy changes to provide for calorie
      posting at the point of purchase could increase customer awareness of the
      calories in these beverages; modifying standard formulations of blended coffee
      beverages, such as using low-fat milk or smaller serving sizes, would also reduce
      calorie content.

PMID- 19754995
TI  - Hospice use among cancer decedents in Alabama, 2002-2005.
AB  - INTRODUCTION: Most studies that describe hospice use among cancer patients use
      the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, which
      has known limitations. We used vital records data to describe patterns of hospice
      use among cancer decedents in Alabama. METHODS: To ascertain hospice use, we
      linked death certificates from 2002 through 2005 for people who died from cancer
      to listings of deaths reported by hospices. To evaluate accessibility of care, we
      calculated straight-line distances between decedent residence at death and the
      hospice providing care. We used these distances to estimate the reach of each
      hospice and identify the number of hospice nonusers residing in these areas.
      RESULTS: During the study period, 52.0% of cancer decedents in Alabama received
      hospice care from 165 hospices. Nearly two-thirds of Alabama counties contain at
      least 1 hospice. Whites (53.6%) used hospice at a significantly higher rate than
      blacks (47.0%), but the rate of use was similar for women (53.2%) and men
      (51.0%). For people who were eligible for Medicare, 53.0% received hospice care.
      The median distance between decedent's residence and the hospice providing care
      was 9.8 miles. This distance was slightly shorter for blacks than whites and
      roughly equal by sex. CONCLUSION: Alabamians use hospice at lower rates than
      observed elsewhere. Barriers to hospice care in Alabama must be identified and
      addressed.

PMID- 19754996
TI  - Fitness-related activities and medical claims related to hospital admissions -
      South Africa, 2006.
AB  - INTRODUCTION: We report on the effect of an incentive-based wellness program on
      medical claims and hospital admissions among members of a major health insurer.
      The focus of this investigation was specifically on fitness-related activities in
      this insured population. METHODS: Adult members of South Africa's largest private
      health insurer (n = 948,974) were grouped, a priori, on the basis of documented
      participation in fitness-related activities, including gym visits, into inactive
      (80%, equivalent to < or =3 gym visits/y), low active (7.0%, 4-23 gym visits/y),
      moderate active (5.2%, 24-48 gym visits/y), and high active (7.4%, >48 gym
      visits/y) groups. We compared medical claims data related to hospital admissions
      between groups after adjustment for age, sex, medical plan, and chronic illness
      benefits. RESULTS: Hospitalization costs per member were lower in each activity
      group compared with the inactive group. This same pattern was demonstrated for
      admissions rates. There was good agreement between level of participation in
      fitness-related activities and in other wellness program offerings; 90% of people
      only nominally engaged in the wellness program also were low active or inactive,
      whereas 84% of those in the high active group also had the highest overall
      participation in the wellness program. CONCLUSION: Participation in fitness
      related activities within an incentive-based health insurance wellness program
      was associated with lower health care costs. However, involvement in fitness
      related activities was generally low, and further research is required to
      identify and address barriers to participation in such programs.

PMID- 19754997
TI  - Validity of self-reported height, weight, and body mass index: findings from the
      National Health and Nutrition Examination Survey, 2001-2006.
AB  - INTRODUCTION: Our study extends previous studies that have evaluated the level of
      bias in self-reported height and weight and corresponding body mass index (BMI).
      Results are evaluated by age, sex, income, race/ethnicity, and BMI
      classifications. METHODS: Analyses are based on the National Health and Nutrition
      Examination Survey (NHANES) from 2001-2006. The sample was 8,208 men and 8,606
      women aged 16 years or older. RESULTS: On average, men overreport their height by
      1.22 cm (0.48 in) and their weight by 0.30 kg (0.66 lbs), and women overreport
      their height by 0.68 cm (0.27 in) and underreport their weight by -1.39 kg (-3.06
      lbs). Overreporting of height significantly increases with age after age 50 for
      men and after age 60 for women. Overreporting of weight in men is significant in
      the age groups 16 to 49 years and 70 years or older. Women significantly
      underreport their weight in each age group but more so in the age group 16 to 49
      years, followed by 50 to 69 years, and then 70 years or older. Men are more
      likely than women to think their weight is about right if they are at a normal
      weight or are overweight or obese, but women are more likely to think their
      weight is about right if they are underweight. CONCLUSION: Men and women
      significantly overreport their height, increasingly so at older ages. Men tend to
      overestimate their weight, but women underreport their weight, more so in younger
      ages. Corresponding BMI is underestimated, more so for women than for men at each
      age and increasingly so with older age for both sexes.

PMID- 19754998
TI  - Randomized controlled trial of a mailed toolkit to increase use of body mass
      index percentiles to screen for childhood obesity.
AB  - INTRODUCTION: Despite epidemic increases in childhood obesity rates, many
      providers fail to diagnose obesity. Body mass index (BMI)-for-age percentiles are
      the recommended screening test. We evaluated whether mailing a toolkit to
      physicians would increase use of sex-specific BMI-for-age percentiles to screen
      for childhood obesity. METHODS: We assigned a random sample of family physicians
      and pediatricians from New York State's medical licensing database to either
      intervention or control groups in the summer of 2004. At baseline and at follow
      up, we sent physicians a survey that asked how often they used various screening
      methods to identify childhood obesity. Between the surveys, we sent physicians in
      the intervention group a toolkit that consisted of professional guidelines for
      childhood obesity screening, a tool for calculating BMI, BMI-for-age growth
      charts, and educational information. RESULTS: At follow-up, more physicians in
      the intervention group than in the control group reported using BMI percentiles
      to screen for childhood obesity. Compared with physicians in the control group,
      physicians in the intervention group had a larger increase in their routine use
      of BMI percentiles to screen children aged 2 to 5, 6 to 11, and 12 to 20 years,
      although the differences in the older 2 groups did not attain statistical
      significance. CONCLUSION: Directly mailing an educational toolkit to physicians
      can have a small but positive effect on clinical practice.

PMID- 19754999
TI  - Promoting dietary change among state health employees in Arkansas through a
      worksite wellness program: the Healthy Employee Lifestyle Program (HELP).
AB  - INTRODUCTION: Maintaining a healthy and productive workforce is essential for
      employers in public and private sectors. Poor nutrition and obesity contribute to
      chronic diseases and influence health care costs and productivity. Research
      indicates that eating a healthy diet is associated with lower body mass index and
      reduced risk for developing chronic disease. METHODS: The Arkansas Department of
      Health implemented the Healthy Employee Lifestyle Program to encourage wellness
      among state health employees. During the pilot year, participants completed a
      health risk assessment at baseline and again after 1 year that assessed diet and
      physical activity, other health risk factors, and readiness to make behavioral
      changes. Participants were encouraged to eat healthfully, participate in regular
      exercise, report health behaviors using a Web-based reporting system, accumulate
      points for healthy behaviors, and redeem points for incentives. Differences in
      participants' (n = 214) reported dietary behaviors between baseline and follow-up
      were assessed using chi2 analyses and tests of symmetry. RESULTS: Consumption of
      sweets/desserts, fats, protein, grains, processed meats, and dairy did not differ
      significantly from baseline to follow-up. However, at follow-up more participants
      reported eating 3 or more fruits and vegetables per day than at baseline and
      being in the action and maintenance stages of readiness to change for eating 5 or
      more fruits and vegetables per day and for eating a diet low in fat. CONCLUSION:
      Further study is needed to examine physical activity and other health risk
      factors to determine whether the program merits a broader dissemination.

PMID- 19755000
TI  - Assessing calcium intake in postmenopausal women.
AB  - INTRODUCTION: Because foods fortified with calcium are increasingly available,
      the calcium content of calcium-fortified foods may not be adequately captured in
      traditional assessments of dietary intake, such as dietary records analyzed with
      commercially available software. The primary objective of our study was to design
      and test a calcium-focused food frequency questionnaire (CFFFQ) including foods
      naturally rich in calcium and calcium-fortified foods. Secondary objectives were
      to review calcium sources and adequacy of intake in black and in white
      postmenopausal women. METHODS: We studied a convenience sample of 46 black and
      139 white postmenopausal women (mean [SD] age 69.4 [5.8] years). Participants
      completed a multiple-pass interview for 24-hour recall of foods eaten and the 46
      item CFFFQ. RESULTS: The correlation between measures for total daily calcium
      intake was moderately strong (r = 0.53, P < .001). The CFFFQ estimated greater
      total daily calcium intake than did the 24-hour recall (mean [SD], 1,021 [624]
      mg/d vs 800 [433] mg/d, P < .001). As daily calcium intake increased, the 24-hour
      recall increasingly underreported calcium (r = 0.41, P < .001) compared with the
      CFFFQ. Cross-tabulation and Chi2 analyses found that the CFFFQ had greater
      specificity for lower calcium intakes. For calcium classified by food groups,
      there was moderate correlation for dairy (r = 0.56, P < .001) and fruits (r =
      0.43, P < .001). The CFFFQ overestimated mean total calcium compared with the 24
      hour recall by 221 mg/d (P < .001), including within racial groups (195 mg/d for
      black women, P = .04, and 229 mg/d for white women, P < .001). Dairy was the
      primary calcium source for both groups (55% of intake for black women and 57% of
      intake for white women). CONCLUSION: The CFFFQ can be used to identify
      postmenopausal women with inadequate calcium intakes (<800 mg/d) and to identify
      key sources of dietary calcium. Older black women consume less daily calcium than
      do older white women.

PMID- 19755001
TI  - Using small-area estimation to describe county-level disparities in mammography.
AB  - INTRODUCTION: Breast cancer control efforts could benefit from estimating
      mammography prevalence at the substate level because studies have primarily
      analyzed health survey data at the national and state levels. The purpose of this
      study was to evaluate the extent to which geographic disparities exist in
      mammography use across counties in the contiguous United States. METHODS: We
      estimated county-level prevalence of recent mammography (past 2 years) for women
      aged 40 to 79 years by using synthetic regression, a small-area estimation
      method. The 2000 Behavioral Risk Factor Surveillance System (BRFSS), 2000 Census,
      Area Resource File, and Food and Drug Administration mammography facility data
      were merged by BRFSS respondents' county of residence. We conducted separate
      analyses to produce county-level prevalence estimates for each race and age
      group. RESULTS: Mammography use varied geographically, and the magnitude of
      geographic disparities differed by race and age. Nonwhite women showed the lowest
      prevalence of mammography and widest range in county-level estimates. Women aged
      40 to 49 had generally lower prevalence than other age groups, while women aged
      65 to 79 showed the greatest variation in county-level mammography estimates.
      CONCLUSION: Small-area estimation using BRFSS data is advantageous for
      surveillance of mammography use at the county level. This method allows
      documentation of geographic disparities and improves our understanding of the
      spatial distribution of mammography prevalence. Future interventions should
      consider this county-level geographic variation, targeting women in the neediest
      counties.

PMID- 19755002
TI  - Accuracy of Veterans Affairs databases for diagnoses of chronic diseases.
AB  - INTRODUCTION: Epidemiologic studies usually use database diagnoses or patient
      self-report to identify disease cohorts, but no previous research has examined
      the extent to which self-report of chronic disease agrees with database diagnoses
      in a Veterans Affairs (VA) health care setting. METHODS: All veterans who had a
      medical care visit from October 1, 1996, through May 31, 1998, at any of the
      Veterans Integrated Service Network 13 facilities were surveyed about physician
      diagnosis of chronic obstructive pulmonary disease (COPD)/asthma, depression,
      diabetes, and heart disease. Four administrative case definitions (data from VA
      databases) consisting of combinations of International Classification of
      Diseases, Ninth Revision, codes and disease-specific medication data were
      compared with self-report of each disease to assess sensitivity, specificity,
      positive and negative predictive values, area under receiver operating
      characteristics curve, and kappa statistic. RESULTS: Sensitivity for
      administrative definitions compared with self-report of physician diagnosis was
      24% to 54% for COPD/asthma, 25% to 47% for depression, 27% to 59% for heart
      disease, and 64% to 78% for diabetes. Specificity was 88% to 100% for all
      diseases. The kappa statistic showed fair agreement for COPD/asthma, depression,
      and heart disease and substantial agreement for diabetes. CONCLUSION: Diagnoses
      identified from databases agree with self-report for diabetes but not
      COPD/asthma, depression, or heart disease in a VA health care setting.

PMID- 19755003
TI  - Evidence-based interventions and screening recommendations for colorectal cancer
      in comprehensive cancer control plans: a content analysis.
AB  - INTRODUCTION: Colorectal cancer is the third most commonly diagnosed cancer and
      third leading cause of cancer death in the United States. The extent to which
      Comprehensive Cancer Control (CCC) programs in states, tribal governments and
      organizations, territories, and Pacific Island jurisdictions address evidence
      based recommendations and interventions for colorectal cancer in their CCC plans
      is largely unknown. METHODS: We downloaded CCC plans posted on the Cancer Control
      PLANET Web site for review. We searched the plans for key terms, identifying
      potential evidence-based content surrounding colorectal cancer prevention and
      early detection. Content was abstracted for further review and classification.
      RESULTS: Of 55 plans reviewed, 54 (98%) referred to evidence-based
      recommendations or interventions for colorectal cancer or indicated they intended
      to refer to the evidence base when developing programs. More than 57% (n = 31) of
      programs referred to the American Cancer Society guidelines, 41% (n = 22)
      referred to the United States Preventive Services Task Force, and 11% (n = 6)
      referred to the Guide to Community Preventive Services. Few programs mentioned
      Research Tested Intervention Programs (n = 1), National Cancer Institute's
      Physician Data Query (n = 4), Cochrane Reviews (n = 2), or Put Prevention Into
      Practice (n = 2) in reference to evidence-based interventions for colorectal
      cancer prevention. CONCLUSION: Most CCC programs discussed either evidence-based
      screening guidelines or interventions in their cancer plans, although many
      mentioned this information exclusively as background information. We recommend
      that program planners be trained to locate evidence-based interventions and use
      consistent common language to describe them in their plans. CCC program planners
      should be encouraged to conduct and publish intervention studies.

PMID- 19755004
TI  - Nutrition literacy status and preferred nutrition communication channels among
      adults in the Lower Mississippi Delta.
AB  - INTRODUCTION: The objective of this cross-sectional study was to examine the
      nutrition literacy status of adults in the Lower Mississippi Delta. METHODS:
      Survey instruments included the Newest Vital Sign and an adapted version of the
      Health Information National Trends Survey. A proportional quota sampling plan was
      used to represent educational achievement of residents in the Delta region.
      Participants included 177 adults, primarily African Americans (81%). Descriptive
      statistics, chi2 analysis, analysis of variance, and multivariate analysis of
      covariance tests were used to examine survey data. RESULTS: Results indicated
      that 24% of participants had a high likelihood of limited nutrition literacy, 28%
      had a possibility of limited nutrition literacy, and 48% had adequate nutrition
      literacy. Controlling for income and education level, the multivariate analysis
      of covariance models revealed that nutrition literacy was significantly
      associated with media use for general purposes (F = 2.79, P = .005), media use
      for nutrition information (F = 2.30, P = .04), and level of trust from nutrition
      sources (F = 2.29, P = .005). Overall, the Internet was the least trusted and
      least used source for nutrition information. Only 12% of participants correctly
      identified the 2005 MyPyramid graphic, and the majority (78%) rated their dietary
      knowledge as poor or fair. CONCLUSION: Compared with other national surveys,
      rates of limited health literacy among Delta adults were high. Nutrition literacy
      status has implications for how people seek nutrition information and how much
      they trust it. Understanding the causes and consequences of limited nutrition
      literacy may be a step toward reducing the burden of nutrition-related chronic
      diseases among disadvantaged rural communities.

PMID- 19755005
TI  - The Latino Health Insurance Program: a pilot intervention for enrolling Latino
      families in health insurance programs, East Boston, Massachusetts, 2006-2007.
AB  - BACKGROUND: Thirteen percent of Latinos in Massachusetts lack health insurance,
      the highest rate of any ethnic or racial group. Families without health insurance
      are more likely to be in poor or fair health, to lack a regular medical provider,
      and to not have visited a medical provider in the past year. CONTEXT: The Latino
      Health Insurance Program is designed as a response both to the high rate of
      uninsurance among Latinos in Boston and to the multiple obstacles that keep
      Latino parents from applying for insurance for their families. METHODS: In 2006,
      we designed and implemented a culturally competent model of health insurance
      outreach, education, enrollment and maintenance, and referral for primary care
      and social services for Latino families. CONSEQUENCES: Year 1 results of the
      Latino Health Insurance Program are promising. Six community members were hired
      and trained as case managers. A total of 230 children and adults were enrolled or
      re-enrolled in health insurance programs and received other needed services.
      Retention was near 100% after 1 year. INTERPRETATION: The Latino Health Insurance
      Program may serve as a model health insurance access program that can be adapted
      by community-based organizations and also can be incorporated into public agency
      programs for Latinos and other immigrant and minority groups. The program
      continues to serve East Boston residents and was expanded in 2008.

PMID- 19755006
TI  - Sustainability of the Pacific Diabetes Today coalitions.
AB  - BACKGROUND: The prevalence of diabetes is unusually high among the indigenous
      peoples of Hawaii and the US-associated Pacific Islands. Although diabetes
      programs developed elsewhere have been tried in these Pacific Islander
      communities, they have not been sustained. Research suggests that program
      sustainability is enhanced by the presence of a champion, the fit of the program
      in an organization, and assistance from stakeholders. CONTEXT: In 1998, the
      Pacific Diabetes Today Resource Center, funded by the Centers for Disease Control
      and Prevention, applied a community-empowerment approach to diabetes programming,
      providing training and technical assistance to coalitions in 11 US-associated
      Pacific Islands communities. When funding ended in 2004, many of the diabetes
      programs continued. In 2008, we revisited the 11 communities to examine the
      vitality of their diabetes coalitions and factors that were known to sustain the
      programs. METHODS: We interviewed coalition representatives in each of the 11
      communities about diabetes-related programming developed from 1999 through 2003
      and factors influencing sustainability of diabetes-related activities.
      CONSEQUENCES: Coalitions that continued the diabetes programming they developed
      for or adapted to their communities had community leaders (or champions), found
      supportive organizational homes for the programs, and had assistance. Four case
      studies show how these factors affected successful coalitions. INTERPRETATION:
      Freedom to adapt programs to new cultural contexts was a key factor in sustaining
      diabetes programs in the region.

PMID- 19755007
TI  - A diabetes self-management program designed for urban American Indians.
AB  - BACKGROUND: Although the American Indian population has a disproportionately high
      rate of type 2 diabetes, little has been written about culturally sensitive self
      management programs in this population. CONTEXT: Community and clinic partners
      worked together to identify barriers to diabetes self-management and to provide
      activities and services as part of a holistic approach to diabetes self
      management, called the Full Circle Diabetes Program. METHODS: The program
      activities and services addressed 4 components of holistic health: body, spirit,
      mind, and emotion. Seven types of activities or services were available to help
      participants improve diabetes self-management; these included exercise classes,
      educational classes, and talking circles. CONSEQUENCES: Ninety-eight percent of
      program enrollees participated in at least 1 activity, and two-thirds
      participated in 2 or more activities. Program participation resulted in a
      significant improvement in knowledge of resources for managing diabetes.
      INTERPRETATION: The Full Circle Diabetes Program developed and implemented
      culturally relevant resources and supports for diabetes self-management in an
      American Indian population. Lessons learned included that a holistic approach to
      diabetes self-management, community participation, and stakeholder partnerships
      are needed for a successful program.

PMID- 19755008
TI  - All-cause mortality in Tianjin, China, 1999-2004.
AB  - INTRODUCTION: We analyzed trends of major causes of death in Tianjin, China, from
      1999 through 2004 to better inform disease prevention and control programs and
      policies. METHODS: To report all-cause deaths among Tianjin residents from 1999
      through 2004, we standardized mortality rates to the world population in 2000. We
      analyzed age, sex, and geographic distribution of deaths from different causes
      and the leading causes of death in Tianjin. RESULTS: The 5 leading causes of
      death in Tianjin were cardiovascular disease, cerebrovascular disease, malignant
      neoplasm, chronic lower respiratory disease, and injuries and poisoning.
      Mortality in Tianjin declined from 0.60% in 1999 to 0.48% in 2004.
      Noncommunicable diseases accounted for more than 80% of all deaths. Infant and
      maternal mortality in Tianjin were low. Life expectancy of Tianjin residents
      increased every year but was consistently longer in women. When deaths from the
      main chronic diseases are not considered, life expectancy lengthens
      substantially. CONCLUSION: Chronic diseases are the leading cause of death in
      Tianjin, China. China should commit additional resources to supporting chronic
      disease prevention and control programs, including proven special health
      promotion projects.

PMID- 19755009
TI  - Celebrating 10 years of the National Comprehensive Cancer Control Program, 1998
      to 2008.

PMID- 19755010
TI  - Epidemiology, public health, and public policy.

PMID- 19755011
TI  - Disentangling the risks associated with weight status, diet, and physical
      activity.

PMID- 19755012
TI  - Using a representative sample of elementary school students to determine the
      statewide prevalence of childhood overweight and obesity in Utah.
AB  - Utah's Height and Weight Measurement Project was conducted with elementary school
      students periodically from 2002 to 2008. The 2002 pilot project was performed to
      establish variability rates between schools and within schools. It allowed us to
      accurately determine both the sample size and the number of schools that were
      required to calculate a reliable statewide estimate based on a random sample of
      schools and to establish sentinel grades. The sentinel grades identified were
      grades 1, 3, and 5. Use of randomly selected classes in the sentinel grades
      resulted in decreased sample size and less school disruption while maintaining
      sufficient precision. Standardized, calibrated equipment was purchased and given
      to school nurses for safekeeping. Lessons learned included establishing strong
      relationships with partners, especially school nurses, and obtaining support from
      upper management at the schools, school districts, and the Utah Department of
      Health. A significant difference in participation rates and obesity rates at the
      individual school level was observed depending on parental consent type; active
      consent was associated with lower student participation rates and lower observed
      obesity rates. Data were presented to both participating and nonparticipating
      schools, school nurses, district superintendents, and principals. For
      surveillance purposes, sampling is an efficient, cost-effective way to estimate
      childhood overweight and obesity rates.

PMID- 19755013
TI  - Monitoring prehospital stroke care in Utah to assess the feasibility of using EMS
      data for surveillance.
AB  - Many states are developing data systems that use the data elements from the
      National Emergency Medical Services Information System (NEMSIS) to monitor
      prehospital stroke care. To explore the feasibility of using emergency medical
      services data to monitor prehospital stroke care in Utah, the Heart Disease and
      Stroke Prevention Program and the state emergency medical services agency
      identified variables that could potentially be used to describe prehospital
      stroke care and explored the actual data from the first 16 months since inception
      of a system compatible with NEMSIS. We were able to develop a case definition for
      possible stroke and to describe modes of response, response times, destination
      hospitals, and stroke screening practices. Although not all emergency medical
      services agencies in Utah used the system and the data were not always complete
      for each stroke case, it was feasible to design a basic surveillance system for
      prehospital stroke care by using the data.

PMID- 19755014
TI  - Risk perceptions and behavior among hospitalized patients with smoking-related
      diseases.

PMID- 19755015
TI  - Comprehensive cancer control in the eye of Hurricane Katrina.

PMID- 19755016
TI  - Cell apoptosis during the cloacal embryonic development in rats with anorectal
      malformations.
AB  - OBJECTIVE: In the normal embryonic development of anorectum, apoptosis plays an
      important role. To explore the role of apoptosis in anorectal malformations
      (ARM), this study investigated cell apoptosis during the cloacal embryonic
      development in ARM embryos. METHODS: ARM embryos were induced by intragastric
      administration of ethylenethiourea (125 mg/kg) for pregnant rats on embryonic day
      10 (E10). The distribution of apoptotic cells in the cloaca was ascertained by
      hematoxylin and eosin and TUNEL staining in the normal control embryos (n=102)
      and ARM embryos (n=147) on E13, E13.5, E14, E15 and E16. RESULTS: On E13,
      apoptotic cells were detected in the urorectal septum of rat embryos in the
      control group. With the development of embryos, the number of apoptotic cells in
      the mesenchyme of urorectal septum gradually increased and a large number of
      apoptotic cells were seen in the dorsal rectal mesenchyme. On E14, apoptotic
      cells appeared at the terminal rectum and the dorsal cloacal membrane. On E15,
      the urorectal septum fused with the cloacal membrane and apoptotic cells in the
      urorectal septum mesenchyme continuously extended down to the fusion region.
      Compared with the control group, apoptotic cells in the urorectal septum, the
      dorsal rectal mesenchyme and the cloacal membrane of the ARM rat embryos were
      significantly reduced during the embryonic development. The development of the
      urorectal septum was delayed and it did not fuse with the cloacal membrane in ARM
      embryos. CONCLUSIONS: During the embryonic development of cloaca, abnormal
      apoptosis in the urorectal septum, the dorsal rectal mesenchyme and the cloacal
      membrane may be one of the reasons for anorectal malformations. The proper
      regulation of cell apoptosis may be one of the key mechanisms for normal
      development of anorectum in the embryonic stage.

PMID- 19755017
TI  - [Relationship between glucocorticoid receptors and glucocorticoid resistance in
      children with idiopathic thrombocytopenia purpura].
AB  - OBJECTIVE: To identify the relationship between the expression of alpha and beta
      isoforms of glucocorticoid receptors (GR) in peripheral blood mononuclear cells
      (PBMC) and glucocorticoid resistance in children with idiopathic thrombocytopenia
      purpura (ITP). METHODS: Real-time PCR was used to detect the expression of GR
      alpha and GR beta mRNA in PBMC from 30 children with ITP (glucocorticoid
      sensitive, n=18; glucocorticoid-resistant, n=12) and 10 healthy children (control
      group). Enzyme immunoassay was used to measure plasma levels of total
      glucocorticoids. RESULTS: There were no significant differences in PBMC GR alpha
      mRNA levels among the glucocorticoid sensitive, the glucocorticoid-resistant and
      the control groups. Compared with the glucocorticoid-sensitive and the control
      groups, the expression of GR beta mRNA in the glucocorticoid-resistant group was
      significantly up-regulated (p<0.01). Plasma total glucocorticoids level in the
      glucocorticoid-resistant group was found to be much higher than that in the
      glucocorticoid-sensitive and the control groups (p<0.01). CONCLUSIONS: The up
      regulated expression of GR beta mRNA may associated with glucocorticoid
      resistance in children with ITP.

PMID- 19755018
TI  - [Expression of vascular endothelial growth factor is related to microvessel
      injury of renal interstitium in children with Henoch Schonlein purpura
      nephritis].
AB  - OBJECTIVE: To investigate the relationship between vascular endothelial growth
      factor (VEGF) expression and microvessel injury of renal interstitium in children
      with Henoch-Schonlein purpura nephritis (HSPN). METHODS: Thirty-two children with
      HSPN and who had not received glucocorticoid or immunodepressants treatment
      before hospitalization were enrolled. Five children undergoing nephrectomy due to
      renal trauma were used as the control group. Renal samples were stained by
      hematoxylin and eosin and renal pathological changes were evaluated semi
      quantitatively. CD34 and VEGF expression was detected by immunohistochemistry.
      CD34 was used as the marker for endothelial cells of renal microvessels. The
      microvessel density (MVD) was calculated by CD34 immunostaining. RESULTS:
      Compared with the control and the renal pathological grade II HSPN groups, MVD in
      the grade III and above HSPN groups decreased significantly, with an obvious
      reduction in MVD with the increased renal pathological grade (p<0.05). The renal
      microvessel score in the grades IIIa, IIIb, IV, and V HSPN groups decreased
      obviously compared with that in the control group. The renal microvessel score
      decreased with the increased renal pathological grade (p<0.05). VEGF expression
      in the grade II HSPN group was higher (p<0.05), while that in the grades IV and V
      HSPN group was lower than that in the control group (p<0.05). VEGF expression in
      the HSPN group showed a significant reduction with the increased renal
      pathological grade (p<0.05). There was a positive correlation between VEGF
      expression and MVD in renal tissue in the HSPN group (r=0.935, p<0.01).
      CONCLUSIONS: The decreased expression of VEGF may be responsible for the renal
      pathological damage and microvessel injury in HSPN.

PMID- 19755019
TI  - [Expression of blood Toll-like receptors and cytokines in children with recurrent
      herpes simplex].
AB  - OBJECTIVE: This study examined the expression of Toll-like receptors (TLR) in
      peripheral blood mononuclear cells (PBMC) and serum levels of IL-6, IL-10 and TNF
      alpha in children with recurrent herpes simplex, in order to investigate the role
      of TLR2 and TLR9 in recurrent herpes simplex. METHODS: The expression of TLR2 and
      TLR9 in PBMC was examined by flow cytometer, and serum levels of IL-6, IL-10 and
      TNF-alpha were detected using ELISA in 22 children with recurrent herpes simplex
      and in 13 age-matched healthy volunteers. RESULTS: The expression of both TLR2
      and TLR9 obviously increased in children with recurrent herpes simplex compared
      with that in healthy controls (p<0.01). Serum levels of IL-6 and IL-10 increased,
      while serum TNF-alpha levels decreased significantly in children with recurrent
      herpes simplex compared with those in healthy controls (p<0.01). There were
      positive correlations between TLR2 and TLR9 expression and serum IL-6 and IL-10
      levels in children with recurrent herpes simplex (p<0.01). CONCLUSIONS: TLR2 and
      TLR9 in PBMC may participate in the recognition of herpes simplex virus and
      activate the signal pathway of TLR in children with recurrent herpes simplex. The
      production and release of IL-6 and IL-10 might be mediated by TLR2 and TLR9.

PMID- 19755020
TI  - [Survey on parental cognition condition on allergic diseases and information
      needs].
AB  - OBJECTIVE: It is widely agreed that comprehensive parental advice and education
      is a cornerstone of allergic disease management. This study was designed to
      investigate the parental cognition condition on allergic diseases and information
      needs, so that medical staff can carry on related education and prevention work
      for children' s parents more efficiently. METHODS: A total of 357 parents from
      the department of child health care were randomly enrolled. A cross-sectional
      study was carried out using a self-designed questionnaire. Descriptive
      statistical analysis, logistic regression model and t test were used to analyze
      the survey results. RESULTS: Three hundred and fifty (98.0%) effective responses
      were received to the questionnaires. Fifty-six percent of the parents did not
      know that asthma was one of the stages in an allergic disease. Seventy-two
      percent of the parents did not know the fact that allergic disease could manifest
      as diarrhea. The majority of the parents (70.9%) thought that the most common
      food leading to allergy was seafood, and 37.4% of parents thought that if a child
      was allergic to some food, then he or she should not eat the food for life.
      Almost all of the parents (97.7%) required information on allergic diseases and
      53% of the parents wanted to understand clinical manifestations of allergic
      diseases. There were statistical significances in the needs to information on
      clinical manifestations of allergic diseases among parents with different
      education levels (OR=2.042, p<0.05). The need for knowledge of allergic diseases
      in parents with an allergic disease or an allergic family history were different
      from the parents without (OR=8.045, p<0.05). Listening to lectures and receiving
      education handbooks on allergic diseases from doctors or health care workers were
      regarded as essential by parents. CONCLUSIONS: Parental knowledge about allergic
      diseases is limited, and some of the knowledge is wrong. The parents want much
      information about allergic diseases. It is necessary to provide education and
      prevention programs on allergic diseases for parents through various ways.

PMID- 19755021
TI  - [Application of damage control surgery in serious pediatric abdominal surgery].
AB  - OBJECTIVE: Damage control surgery (DCS) deals with the complex surgical problems
      by stages. This study investigated the application of DCS in serious pediatric
      abdominal surgery. METHODS: The clinical data of 49 children with serious
      abdominal diseases (age: 4 months to 10 years) were retrospectively studied. Of
      them, 32 children underwent damage control surgery (DCS) and 17 children
      underwent conventional operation. The preoperative critical severity score (CSS),
      postoperative temperature, blood pH and prothrombin time (PT), and the treatment
      outcome were compared between the DCS and the conventional operation groups.
      RESULTS: No significant difference was found in the preoperative CSS between the
      two groups. There were significant differences in postoperative blood pH and PT
      values between the two groups (p<0.05). As for postoperative temperature, there
      was no statistical difference between the two groups, yet the tendency of
      temperature recovery in the DCS group was milder than that in the conventional
      operation group. Twenty-seven children (84.4%) were successfully cured in the DCS
      group, while 9 children (52.9%) in the conventional operation group (p<0.05).
      CONCLUSIONS: The curative effect of DCS surpasses the conventional operation in
      children with serious abdominal diseases, suggesting that DCS is of value in the
      management of serious pediatric abdominal diseases.

PMID- 19755022
TI  - [Assessment of insular development in small for gestational age infants].
AB  - OBJECTIVE: To study the insular development of small for gestational age (SGA)
      infants. METHODS: The insular area and circle were measured by cerebral
      ultrasonography in 92 SGA infants. The results were compared with those from 109
      appropriate for gestational age (AGA) infants. RESULTS: The insular area and
      circle were positively correlated with the birth weight and gestational age in
      SGA infants. The insular area in SGA infants with a gestational age of either >37
      weeks (451 +/- 92 mm2 vs 516 +/- 116 mm2; p<0.01) or < or = 34 weeks (248 +/- 78
      mm2 vs 314 +/- 80 mm2; p<0.01) was significantly less than that in the AGA
      infants. The insular circle in SGA infants with a gestational age of >37 weeks
      was also significantly less than that in the AGA infants (92 +/- 11 mm vs 97 +/-
      11 mm; p<0.05). CONCLUSIONS: The insular development of SGA infants seems to be
      immature. The insular development may be assessed based on the insular area and
      circle measured by cerebral ultrasonography.

PMID- 19755023
TI  - [Investigation of birth state and disease spectrum in 1,434 hospitalized
      neonates].
AB  - OBJECTIVE: To investigate the birth state of neonates and the disease spectrum of
      hospitalized neonates from a primary hospital, and compare with the national data
      of the same period. METHODS: A retrospective investigation was carried out in
      1,434 neonates born or hospitalized in this hospital from January 2005 to
      December 2005. RESULTS: During the investigation period, there were 1,100
      neonates born in the department of obstetrics. The incidence of premature birth
      was 2.3%. The caesarean birth accounted for 54.2%, significantly higher than the
      national average (49.2%, p<0.01). The neonatal mortality was 0.2%. The incidences
      of antepartum hemorrhage, threatened abortion, and pregnancy infection in preterm
      infant' s mothers were significantly higher than those in full-term infant' s
      mothers. A total of 344 neonates were admitted to the department of pediatrics
      during the investigation period. Preterm infants accounted for 38.0% which was
      higher than the national average (26.2%; p<0.01). Beside preterm infants,
      asphyxia, respiratory distress syndrome (RDS), sepsis and intracranial hemorrhage
      were shown to have a significantly higher proportion than the national averages.
      The mortality of hospitalized neonates was 0.9%. CONCLUSIONS: The higher cesarean
      section rate should be controlled in our hospital. Prenatal health care and fetal
      monitoring should be strengthened to decrease the incidence of premature birth,
      RDS, sepsis and intracranial hemorrhage, thus reducing the mortality of neonates.

PMID- 19755024
TI  - [Clinical evidence for the pharmacological therapy in newborn infants with
      hypoxic-ischemic encephalopathy].
AB  - OBJECTIVE: Pharmacological intervention is an important means for the treatment
      of hypoxic-ischemic encephalopathy (HIE). As meta-analyses and randomized
      controlled clinical trials based on evidence-based medicine are able to provide
      the most reliable evidence for clinical practice, this study searched several
      databases in order to find the clinical evidence for the pharmacological
      treatment of neonatal HIE. METHODS: Meta-analyses and randomized (or quasi
      randomized) controlled trials (RCT) for pharmacological therapy of HIE in term or
      late preterm newborn infants were searched from the databases of MEDLINE, EMBASE,
      Oxford Neonatal Group and Cochrane Library. The relevant literatures were
      statistically analyzed. RESULTS: Four Meta-analyses and thirteen RCTs were found
      to be involved in barbiturate, allopurinol, magnesium sulfate, mannitol, naloxone
      and dopamine therapy. None of the drugs could significantly decrease the
      mortality and the incidence of seizure or severe neurodevelopmental disabilities
      in newborn infants with HIE. CONCLUSIONS: Current clinical evidence indicates
      that no individual drug could decrease mortality and improve the
      neurodevelopmental outcomes in infants with HIE. Problems such as small scale in
      sampling and discrepancy in the identification of drug efficacy which exist in
      the clinical trials might lead to the uncertain effect of the drugs, and large
      sized and collaborative clinical trials are needed in the future.

PMID- 19755025
TI  - [Serum leptin level and its association with bone mineral density in obese
      children].
AB  - OBJECTIVE: To investigate serum leptin level and its relationship with bone
      mineral density in obese children from Changsha City. METHODS: One hundred and
      nineteen obese children and 103 normal children aged 7 to 12 years from five
      primary schools of Changsha City were enrolled. Obesity was assessed based on the
      body mass index (BMI). Dual energy X-ray absorptiometry (DEXA) was used to
      determine bone mineral density (BMD) and body composition. Serum leptin level was
      measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: The obesity
      group had higher height, weight, BMI, waist circumference and waist to hip ratio
      (WHR) compared with the normal group (p<0.01). BMD, bone mineral content (BMC),
      lean mass (LM), fat mass (FM), percentage of body fat (%BF) and leptin
      concentration in the obesity group were significantly higher than those in the
      normal group (p<0.01). Serum leptin level was positively correlated with BMD,
      BMC, LM and FM (r=0.528-0.903, p<0.01). Multiple stepwise regression analysis
      indicated that BMI and %BF were independent influencing factors for serum leptin
      level. CONCLUSIONS: Obese children have higher serum leptin level. Serum leptin
      concentration is significantly correlated with BMD and body composition. BMI and
      %BF are independent influencing factors for serum leptin level in children.

PMID- 19755026
TI  - [Hyperbaric oxygen promotes the migration and differentiation of endogenous
      neural stem cells in neonatal rats with hypoxic-ischemic brain damage].
AB  - OBJECTIVE: To explore the effects of hyperbaric oxygen (HBO) treatment on the
      migration and differentiation of endogenous neural stem cells (NSCs) in neonatal
      rats with hypoxic-ischemic brain damage (HIBD). METHODS: Seven-day-old Sprague
      Dawley rats were randomly divided into the normal control (CON), the HIBD model
      and the HBO groups (HBO treatment was administered at 2 ATA, once daily for 7
      days within 3 hrs after HIBD). HIBD model was prepared according to the classic
      Rice-Vannucci method. BrdU/DCX, BrdU/beta-tubulin, BrdU/GFAP and BrdU/O4
      immunofluorescence were examined by confocal microscopy in the subventricular
      zone (SVZ) and the cortex 7, 14 and 28 days after HBO treatment. RESULTS: The
      BrdU(+)DCX(+) cells in the SVZ (84 +/- 21 cells/mm2) in the HBO group were
      significantly higher than those in the CON group (39 +/- 14 cells/mm2) (p<0.05)
      and the HIBD model group (68 +/- 17 cells/mm2) (p<0.05) 7 days after HBO
      treatment. Fourteen days after HBO treatment, the BrdU(+) DCX(+) cells decreased
      in the SVZ and more cells were observed in the cortex in the HBO group as
      compared with the CON group (p<0.01). The BrdU(+) beta-tubulin(+), BrdU(+)GFAP(+)
      and BrdU(+) O4(+) cells were observed in the cortex, and more BrdU(+)beta
      tubulin(+) and BrdU(+) O4(+) cells were observed in the HBO group as compared
      with the CON and the HIBD model groups (p<0.05) 28 days after HBO treatment.
      CONCLUSIONS: HBO treatment may promote endogenous NSCs to migrate to the cortex
      and differentiate into mature neurocytes in neonatal rats with HIBD.

PMID- 19755027
TI  - [Acetylation of hepatic histone H3 in rats with intrauterine growth retardation].
AB  - OBJECTIVE: To investigate the effects of intrauterine growth retardation (IUGR)
      caused by malnutrition during pregnancy on the acetylation of histone H3 and
      expression of histonedeacetylase1(HDAC1) in the hepar of the adult offspring and
      to explore the relationship between them. METHODS: Male 8-week-old offspring from
      maternal protein-malnutrition dams were studied. The expression of HDAC1 mRNA in
      the hepar was measured by fluorescent quantization RT-PCR. The levels of hepatic
      nuclear HDAC1 protein and acetylation of histone H3/K9 were assessed by Western
      blot. RESULTS: The hepatic HDAC1 mRNA expression in IUGR rats was reduced to 54%
      of that of normal control rats (t=2.042, p<0.05). A decline in nuclear expression
      of HDAC1 protein (438 +/- 47) was also noted when compared with normal controls
      (1,128 +/- 110) (t=2.179, p<0.05). In contrast, the percentage of acetylated
      histone H3/K9 in IUGR rats (17.3 +/- 1.6%) increased significantly compared with
      that of normal control rats (10.5 +/- 1.2%) (t=3.597, p<0.01). The level of
      acetylated histone H3/K9 was negatively correlated with the HDAC1 protein
      concentration (r=-0.781, p<0.01). CONCLUSIONS: Increased hepatic acetylation of
      histone H3 in the IUGR offspring might be caused by decreased HDAC1 expression in
      nuclear protein. This may contribute to the transcription change of some genes in
      the hepar.

PMID- 19755028
TI  - [Comparison of immunomagnetic beads and hespan precipitation for isolation of
      mononuclear cells from umbilical cord blood].
AB  - OBJECTIVE: To compare the characteristics of immunomagnetic beads and hespan
      precipitation for isolation of mononuclear cells (MNCs) from umbilical cord blood
      and try to find a better isolation method for MNCs. METHODS: Fifteen umbilical
      cord blood samples from healthy parturiens were collected between December 2007
      and March 2008. MNCs were isolated using hespan precipitation and CD133
      immunomagnetic beads, respectively. MNCs were identified using the surface marker
      CD34 by flow cytometry on the 30th of primary culture. Growth conditions and
      morphologic changes of primary cells were observed by an inverted microscope.
      RESULTS: The number of MNCs from umbilical cord blood isolated by hespan
      precipitation (15.23 +/- 4.30 x 10(6)/mL) was significantly greater than that by
      CD133 immunomagnetic beads (0.066 +/- 0.027 x 10(6)/mL) (p<0.05). The MNCs
      isolated by hespan precipitation suspended at the culture medium and their growth
      was slow after passage. The growth of MNCs isolated by CD133 immunomagnetic beads
      was kept in a good condition. The CD34 positive rate of MNCs isolated by hespan
      precipitation and immunomagnetic beads was 10.1% and 0.5%, respectively.
      CONCLUSIONS: The hespan precipitation is an effective method for MNCs isolation
      from human umbilical cord blood, but with a cell growth condition below the mark.
      The MNCs isolated by CD133 immunomagnetic beads are in a high purity quotient.

PMID- 19755029
TI  - [Packaging and concentrating of high titer of retrovirus containing IL-4RA].
AB  - OBJECTIVE: To construct a recombination retroviral expression vector pLNC-IL-4RA
      with high efficiency transfection and carrying a screening label. METHODS: IL-4RA
      was inserted into retroviral vector pLNC-Laz to get recombination retroviral
      expression vector pLNC-IL-4RA and then transfected into packaging cell line PA317
      by liposome transfection. The transfected PA317 cells were obtained and amplified
      by G418 pressure screening. The cell culture supernatants containing viruses were
      harvested and the viral titer was determined by NIH3T3 cells infection. RESULTS:
      The G418 resistant clones were titrated and checked for the presence of
      replication virus. The results showed that the highest titer of viral supernatant
      was 1 x 10(4) CFU/mL. Genome DNA isolated from the cell clone of the highest
      titer showed the function gene, IL-4RA cDNA, had integrated into the genome of
      host cells verified by PCR. CONCLUSIONS: The recombination retroviral vector pLNC
      IL-4RA encoding IL-4RA after packaging PA317 cells have higher viral titer. This
      provides a basis for gene treatment of asthma.

PMID- 19755030
TI  - [Misdiagnosis of type 1 diabetes in children: analysis of 22 cases].

PMID- 19755031
TI  - [Efficacy and safety of budesonide/formoterol dry powder inhalation for treatment
      of childhood asthma].

PMID- 19755032
TI  - [Efficacy of manipulative therapy for night waking in children].

PMID- 19755033
TI  - [Efficacy of different dosages of ambroxol hydrochloride in the prevention of
      neonatal respiratory distress syndrome].

PMID- 19755034
TI  - [Efficacy of blood purification therapy for multiple organ dysfunction syndrome
      induced by bee-sting in children].

PMID- 19755035
TI  - [Congenital nephritic syndrome complicated by epilepsy: a case report].

PMID- 19755036
TI  - [Kawasaki disease complicated by autoimmune hemolytic anemia and macrophage
      activation syndrome: a case report].

PMID- 19755037
TI  - [RABL2B gene mutation in a girl with mental retardation and hyperactivity].

PMID- 19755038
TI  - [MN hemolytic disease in a pair of newborn twins].

PMID- 19755039
TI  - [Polyunsaturated fatty acids and attention-deficit hyperactivity disorder].

PMID- 19755040
TI  - [Research advance in the treatment of phenylketonuria].

PMID- 19755041
TI  - [Role of gas signaling molecule hydrogen sulfide in cardiovascular diseases].

PMID- 19755042
TI  - NCCN task force report: management of neuropathy in cancer.
AB  - Neuropathy is a common, often debilitating complication of cancer and its
      treatment. Effective management of this disorder depends on early diagnosis and
      an understanding of its underlying causes in the individual patient. In January
      2009, NCCN gathered a multidisciplinary group to review the literature and
      discuss intervention strategies currently available to patients as well as areas
      that require research efforts. The task force, which comprised experts in
      anesthesiology, medical oncology, neurology, neuro-oncology, neurophysiology,
      nursing, pain management, and rehabilitation, was charged with the goal of
      outlining recommendations for the possible prevention, diagnosis, and management
      of neuropathy. This report documents the proceedings of this meeting with a
      general background on neuropathy and neuropathy in oncology, followed by
      discussions on challenges and research issues, evaluation criteria, and
      management of different symptoms associated with this disorder.

PMID- 19755043
TI  - NCCN Task Force Report: Estrogen Receptor and Progesterone Receptor Testing in
      Breast Cancer by Immunohistochemistry.
AB  - The NCCN Task Force on Estrogen Receptor and Progesterone Receptor Testing in
      Breast Cancer by Immunohistochemistry was convened to critically evaluate the
      extent to which the presence of the estrogen receptor (ER) and progesterone
      receptor (PgR) biomarkers in breast cancer serve as prognostic and predictive
      factors in the adjuvant and metastatic settings, and the ability of
      immunohistochemical (IHC) detection of ER and PgR to provide an accurate
      assessment of the expression of these biomarkers in breast cancer tumor tissue.
      The task force is a multidisciplinary panel of 13 experts in breast cancer who
      are affiliated with NCCN member institutions and represent the disciplines of
      pathology, medical oncology, radiation oncology, surgical oncology, and
      biostatistics. The main overall conclusions of the task force are ER is a strong
      predictor of response to endocrine therapy; ER status of all samples of invasive
      breast cancer or ductal carcinoma in situ (DCIS) should be evaluated by IHC; IHC
      measurements of PgR, although not as important clinically as ER, can provide
      useful information and should also be performed on all samples of invasive breast
      cancer or DCIS; IHC is the main testing strategy for evaluating ER and PgR in
      breast cancer and priority should be given to improve the quality of IHC testing
      methodologies; all laboratories performing IHC assays of ER and PgR should
      undertake formal validation studies to show both technical and clinical
      validation of the assay in use; and all laboratories performing IHC assays of
      hormone receptors in breast cancer should follow additional quality control and
      assurance measures as outlined in the upcoming guidelines from the American
      Society of Clinical Oncology and College of American Pathologists.

PMID- 19755044
TI  - Colon cancer: the new breast cancer.

PMID- 19755045
TI  - Discussing colorectal cancer.

PMID- 19755046
TI  - NCCN Clinical Practice Guidelines in Oncology: colon cancer.

PMID- 19755047
TI  - NCCN Clinical Practice Guidelines in Oncology: rectal cancer.

PMID- 19755049
TI  - Concordance with NCCN Colorectal Cancer Guidelines and ASCO/NCCN Quality
      Measures: an NCCN institutional analysis.
AB  - BACKGROUND: The National Comprehensive Cancer Network (NCCN) Outcomes Database
      was created to assess concordance to evidence- and consensus-based guidelines and
      to measure adherence to quality measures on an ongoing basis. The Colorectal
      Cancer Database began in 2005 as a collaboration among 8 NCCN centers. METHODS:
      Newly diagnosed colon and rectal cancer patients presenting to 1 of 8 NCCN
      centers between September 1, 2005, and May 21, 2008, were eligible for analysis
      of concordance with NCCN treatment guidelines for colorectal cancer and with a
      set of quality metrics jointly developed by ASCO and NCCN in 2007. Adherence
      rates were determined for each metric. Center-specific rates were benchmarked
      against mean concordance rates for all participating centers. RESULTS: A total of
      3443 patients were evaluable. Mean concordance rates with NCCN colorectal cancer
      guidelines and ASCO/NCCN quality measures were generally high ( >or= 90%).
      However, relatively low mean concordance rates were noted for adjuvant
      chemotherapy treatment recommendations within 9 months of diagnosis of stage II
      to III rectal cancer (81%), and neoadjuvant chemoradiation in clinical T4 rectal
      primaries (83%). These low rates of concordance seemed to be consistent across
      centers. CONCLUSIONS: Adherence to guidelines and quality measures is generally
      high at institutions participating in the NCCN colorectal cancer database. Lack
      of documentation, patient refusal, delayed treatment initiation, and lack of
      consensus about whether treatment was essential were the primary reasons for
      nonconcordance. Measurement of concordance and the reasons for nonconcordance
      enable participating centers to understand and improve their care delivery
      systems.

PMID- 19755048
TI  - The challenges of colorectal cancer survivorship.
AB  - With advances in treatment, colorectal cancer (CRC) is being transformed from a
      deadly disease into an illness that is increasingly curable. With this
      transformation has come increased interest in the unique problems, risks, needs,
      and concerns of survivors who have completed treatment and are cancer-free.
      Research has shown that physical and mental quality of life for CRC survivors was
      inferior compared with age-matched individuals without cancer. Although issues
      and symptoms were most prominent during the first 3 years, long-term effects of
      treatment can persist and include fatigue, sleep difficulty, fear of recurrence,
      anxiety, depression, negative body image, sensory neuropathy, gastrointestinal
      problems, urinary incontinence, and sexual dysfunction. The unique challenges and
      issues of CRC survivors can and should be addressed by health care providers and
      the research community to ensure effective interventions and models of care to
      manage these problems. This article discusses what is known about the long-term
      effects of CRC treatment on quality of life, the care of survivors, and existing
      models of survivorship care.

PMID- 19755050
TI  - Experiences with the two incision minimal invasive hip replacement in 150 cases
      with a proximally hydroxyapatite coated implant.
AB  - BACKGROUND: In this retrospective study we describe our experiences in minimally
      invasive two incision total hip replacement (THR). METHODS: We performed 150
      fluoroscopy-assisted two incision minimally invasive THR on 148 patients using a
      proximally coated hydroxyapatite implant. Clinical (Harris Hip Score (HHS),
      surgical time, blood loss, length of hospital stay) and radiographic data (leg
      length discrepancy, cup abduction angle, stem alignment) were collected. RESULTS:
      The HHS increased from 54.7 preoperatively to 92.6 postoperatively. Mean surgical
      time was 103 minutes. Mean intra- operative blood loss was 410 ml. There were 11
      (7.3%) complications including two dislocations (1.3%), one deep wound infection
      (0.7%), three minor calcar fractures (2.0 %), one periprosthetic femur fracture
      (0.7 %), two subsided stems (1.3%) and two femoral nerve palsies (1.3%). One of
      the femoral nerve palsies remained unresolved. The prevent femoral nerve palsies
      we used somato-sensory evoked potentials (SSEP) after the 48th case and there
      were no further nerve palsies. Ten complications were in the first 48 cases. In
      the first 28 cases the anterior skin incision was parallel to the femoral neck
      and then changed to parallel the intertrochanteric line. Mean length of stay was
      2.2 days. Mean cup abduction angle was 39.4 degrees and mean cup anteversion was
      34.6 degrees. CONCLUSION: The initial complication rate can be related to the
      learning curve using a new surgical technique. In the subsequent 102 surgeries
      there was one stem subsidence. The minimally invasive approach in THA remains new
      technique and carries additional risks. Secondary to the learning curve
      comparable short and long term follow up's are necessary.

PMID- 19755051
TI  - [Long-term results of use of the CLS stem in primary total hip arthroplasty].
AB  - PURPOSE OF THE STUDY: The aim of the study was to evaluate the results of primary
      total hip arthroplasty with the use of the CLS stem at 11 to 17 years after
      implantation. MATERIAL AND METHODS: A total of 108 patients (122 hips) in whom a
      CLS stem was used in the 1991-1996 period were evaluated. The group included 34
      men and 74 women, with an average age of 48 years (range, 28-63). The CLS stem
      with a neck-shaft angle of 145 degrees and the CLS expansion cup were used in all
      patients. Clinical outcomes were evaluated by Merle d'Aubigne-Postel score and
      Harris hip score, radiological examination was completed on AP and lateral views
      of the pelvis and the operated hip. RESULTS: The average follow-up was 16.4 years
      (range, 11-17). The average Merle d'Aubigne-Postel score was 14.5 (range, 13.9
      17.0) points and the average Harris hip score was 84.8 (range, 70-99) points.
      Very good or good outcomes were found in 81% of the patients. Three patients
      underwent revision surgery, in one for septic loosening, in one for aseptic
      loosening and in one for varus stem position leading to instability. The
      radiographs evaluated as described by Engh showed 116 stable stems, three fibrous
      stable and three unstable stems. Subsidence of more than 3 mm, without any
      further deterioration, was found in five hips at 12 months post-operatively.
      Seven hips showed one radiolucent line, four showed two radiolucent lines and
      three hips showed three radiolucent lines, all of them being less than 2 mm wide.
      DISCUSSION: Radiographic evidence of a stable stem in 116 hips (116/122) suggests
      a high reliability of the implant. Assessment of radiolucent lines showed 108
      hips without radiographic demarcation and 11 hips with slight demarcation. The
      signs of stress-shielding grade 1 were found in 28 hips. Good results of
      arthroplasty with the CLS stem can be attributed to its three-dimensional wedge
      shaped design that allows for an optimal press-fit in the metaphyseal region. The
      porous surface provides reliable osteointegration. Stress-shielding is prevented
      by optimal stress distribution in the metaphyseal region and by a modulus of
      elasticity of titanium alloy which closely approximates the modulus of elasticity
      of bone. CONCLUSIONS: At 15 years post-operatively, the cumulative probability of
      clinical survivorship of the CLS stem was 98.3 %, and cumulative probability of
      radiographic survivorship was 87.7 %. The advantages of this stem include a
      technically simple implantation, reliable osteointegration and long-term
      stability even in high demanding patients.

PMID- 19755052
TI  - [Total hip replacement from a MIS-AL approach (comparison with a standard
      anterolateral approach)].
AB  - PURPOSE OF THE STUDY: Minimally invasive surgery (MIS) techniques have recently
      become a powerful and effective marketing instruments that are often perceived by
      the patient as the criterion of the surgeon's and institution's standard. In
      addition to studies reporting the benefits of minimally invasive procedures, some
      authors have recently found no such benefits or even pointed out some
      disadvantages. In this paper we present our own view of this issue. Our
      definition of minimally invasive surgery: a minimally invasive procedure is such
      that an optimally placed incision using anatomical intervals without damage to
      muscle insertions allows us to gain a good view of the operating field and to
      safely perform the planned surgery. Because of this optimal approach it is
      possible to make skin incisions shorter. MATERIAL: Between April 21, 2005, and
      December 28, 2006, the first 40 MIS hip procedures were performed at the
      Department of Orthopaedic Surgery of the ILF Bulovka. Forty patients who, in the
      same period, were operated on from an anterolateral standard approach and who met
      the same indication criteria, including age, comprised a control group. In both
      groups all routinely used types of implants were included. METHODS: For objective
      assessment of potential differences between surgical outcomes of the two
      techniques, the following para- meters were recorded: operating time, peri
      operative blood loss, pre- and post-operative Hb levels, Hb level on the first
      post- operative morning, amount of blood drained away with a Redon drain, number
      of anodyne applications (indirect evaluation of post-operative pain) and length
      of hospital stay. The parameters were compared for the cemented and the
      uncemented implants separately. The results were evaluated using the paired t
      test, with the significance level set at a value of p<0.05. RESULTS: A comparison
      of the MIS-AL results with those of the standard total hip replacement procedure
      did not show any significant differences, not even during further follow-up; by
      the end of 2008 no implant failure or necessity of revision arthro- plasty was
      reported. DISCUSSION: So far the only indisputable fact is that all the benefits
      of minimally invasive techniques described until now are merely related to time,
      as they facilitate a faster rate of soft tissue repair; therefore, these
      techniques only shorten recovery and thus speed up return of the operated hip to
      full function. CONCLUSIONS: Based on comparison of the standard anterolateral and
      minimally invasive techniques it can be concluded that the MIS- AL approach is
      effective even without the use of special instrumentation. However, the results
      of this study failed to give unambiguous support to its advantage over the
      classical technique.

PMID- 19755053
TI  - [Bernese periacetabular osteotomy (Ganz procedure). First experience].
AB  - PURPOSE OF THE STUDY: Developmental dysplasia of the hip (DDH), treated either
      conservatively or surgically, may result in a dysplastic acetabulum. To treat
      this after bone maturation is completed, Bernese periacetabular osteotomy, also
      known as the Ganz procedure, has recently been used as the method of choice at
      our department. The evaluation of the first results is presented here. MATERIAL
      AND METHODS: The group evaluated comprised 25 hips (21 female and 4 male) in 22
      patients. Nineteen hips were treated for residual dysplasia of the acetabulum due
      to DDH, and six for a spastic hip. The average age was 26 years (range, 12 to 44)
      and 14 right and 11 left hips were involved On pre- and post-operative
      radiographs the AC index, Wiberg lateral CE angle, Wagner index, improvement in
      Shenton's line, and lateralisation and anteversion of the acetabulum were
      compared. Bernese periacetabular osteotomy is an extensive surgical procedure
      requiring special instrumentation. It may be associated with serious
      complications and has a relatively long learning curve. RESULTS: The average
      follow-up was 18 months (range, 2 to 36). The average duration of surgery was 2
      hours and 44 min (range, 2 to 31/ 2 h). The average values improved in the AC
      index by 24 degrees, lateral CE angle by 29 degrees and Wagner index by 18 %.
      Shenton's line was corrected by surgery in 20 hips and lateral migration in 16
      hips. In two hips lateralisation did not changed. Two serious complications were
      recorded: para-articular ossification requiring excision and concomitant
      acetabular trimming, and great intra-operative blood loss. DISCUSSION: Various
      mechanisms of damage to the hip are discussed and the methods of treatment
      outlined, together with prerequisites for successful surgery. Potential
      complications and their treatment are mentioned. CONCLUSIONS: Bernese
      periacetabular osteotomy makes the range of roofing procedures for hip joint
      treatment wider. These, as well as hip joint reduction techniques, should be
      performed in major specialized centres.

PMID- 19755054
TI  - [Comparison of therapeutic strategies for hip and knee prosthetic joint
      infection].
AB  - PURPOSE OF THE STUDY: Prosthetic joint infection (PJI) is a feared complication
      of total joint arthroplasty. Several strategies have been developed to treat it.
      The purpose of our study was to compare therapeutic strategies for PJI treatment
      published in the literature. MATERIAL AND METHODS: We retrieved around 5,000
      documents concerning this topic, published between January 1960 and November
      2006, from the databases MEDLINE and EMBASE. Using a two-phase selection, 382
      relevant articles were chosen, and full texts were obtained for 302 of them
      (79%). However, only 77 of them fulfilled the criteria for inclusion in our
      study. A total of 645 hips and 1,145 knees could be analyzed. A comparison was
      made of the following procedures: two-stage surgery, one- stage surgery, implant
      removal and long-term antibiotic therapy in hip PJI; two-stage surgery,
      debridement, arthrodesis and long-term antibiotic therapy in knee PJI. The
      criteria used to evaluate successful PJI treatment included the rate of recur-
      rent infection (primary outcome) and the rate of additional surgery (secondary
      outcome). The capability index (c), relative risk (RR), odds ratio and "number
      needed to treat" (NNT) were calculated for both outcomes under study. RESULTS: 1.
      The lowest rate of recurrent PJI was reported for two-stage reimplantation (hips,
      7.4%; knees, 11%), then came one-stage reimplantation for hip PJI (9.2%) and
      arthrodesis for knee PJI (15.6%). 2. The lowest relative risk for the primary
      outcome of this study was found in two-stage reimplantation (RR=0.62 and 0.32 for
      hip and knee PJI, respectively, knee arthrodesis (RR=0.78) and one-stage hip
      reimplantation (RR=1.07). 3. The NNT was negative for two-stage reimplantation
      (NNT = -21.6 and -4.3 for hip and knee PJI, respectively). 4. Compared to long
      term antibiotic therapy, knee debridement had a higher risk of recurrent
      infection (RR, 4.72 versus 1.20) as well as the risk of additional surgery (RR,
      4.41 versus 1.31). However, when the capability index and NNT were used, knee
      debridement achieved better primary outcomes than antibiotic therapy (c=0.0317
      versus 0.0000) and NNT (2.2 versus 26.3). 5. Relative risk for additional surgery
      was the lowest in two-stage reimplantation (RR=0.47 and 0.36 for hip and knee
      PJI, respectively), and the highest in long-term antibiotic therapy for hip PJI
      (RR=6.47). DISCUSSION: The resultant ranking of therapeutic approaches to PJI, as
      found in our study, is not surprising; except for seemingly bet- ter outcomes
      achieved by long-term antibiotic therapy compared to surgical debridement in knee
      PJI. This, among others, shows the need to use more comprehensible statistical
      instruments, such as the capability index, that could provide a more reliable
      evaluation of therapeutic interventions. CONCLUSIONS: A two-stage protocol for
      PJI treatment had the lowest risk for both PJI recurrence and need for additional
      surgery in comparison with all other strategies developed for PJI therapy.
      Therefore, it should be accepted as the method of choice. One-stage hip
      reimplantation is a less reliable approach in which it is inevitable to strictly
      respect the indication criteria. Other methods are either less reliable or
      associated with a high risk of repeat surgeries, or provide functionally
      unacceptable outcomes.

PMID- 19755055
TI  - [Damage control laparotomy in blunt abdominal injury].
AB  - PURPOSE OF THE STUDY: Damage control surgery is one of the major advances in
      surgical techniques used in polytrauma patients in the past 25 years. It is based
      on a foreshortened pre-operative examination during ongoing resuscitation which
      includes surgical intervention in an injured patient with severe hypotension due
      to haemorrhage. In this seven-year retrospective study the authors evaluate the
      results of damage control laparotomy in patients with injury to the abdominal
      organs, retroperitoneum and pelvis. MATERIAL AND METHODS: The evaluated group
      included 21 patients with blunt abdominal trauma who underwent damage control
      laparotomy in the 2001-2007 period. There were 17 men and four women; the age
      range was 17 to 69 years, with an average of 36 years. Damage control laparotomy
      was indicated in the patients with blunt abdominal trauma, or with closed or open
      pelvic fracture, who developed a progressive haemorrhagic shock. RESULTS: Between
      2001 and 2007, a total of 21 922 patients were admitted to the Trauma Centre and
      12 392 operations were performed. However, only in 21 of them (0.1 %) damage
      control laparotomy was indicated. The procedure was most frequently performed for
      liver injury (16 patients), which was associated with multiple injury to the
      other abdominal organs and retroperitoneum in five patients. Further three
      patients were operated on for haemoperitoneum at continual bleeding due to type C
      fracture of the pelvis. In the remaining two patients the damage control
      procedure was chosen to stop persistent bleeding following splenectomy and
      nephrectomy for traumatic rupture. In these 21 patients blunt trauma was part of
      polytrauma (ISS > 15). Repeat surgery was carried out within 48 to 96 hours
      (average, 58 h). Four patients (19 %) died; two due to progressive traumatic
      haemorrhagic shock and two because of brain oedema after concussion. DISCUSSION:
      Damage control surgery has become a fundamental component of surgical strategy
      for severe trauma and has been accepted by surgeons although it cannot be
      evaluated in randomized clinical studies. Survival after damage control
      laparotomy in serious intra-abdominal injuries involved in polytrauma is reported
      in relation to the scoring system values (ISS, GCS), but depends, first of all,
      on blood loss, degree of acidosis and severity of associated injuries, with
      craniocerebral trauma in the first place. CONCLUSIONS: Damage control laparotomy
      is an effective procedure in the treatment of severe trauma to the abdominal
      organs and retroperitoneum in critically injured patients. This time-limited,
      staged surgical intervention is included in resuscitation of patients with
      hypothermia, metabolic acidosis and coagulopathy. The outcome of damage control
      surgery is related to not only the severity of injury, but also experience with
      comprehensive acute care in trauma centres.

PMID- 19755056
TI  - [Os Pisiforme transposition in the treatment of Kienbock's disease - long term
      results].
AB  - PURPOSE OF THE STUDY: One of the methods used for treatment of Kienbock's disease
      is based on transposition of the pisiform bone into free space created by removal
      of the lunate bone. It is performed in patients with stage IIIB to IV, as
      assessed by Lichtmann's score. However, this operative procedure has so far
      lacked an unequivocal assessment of its therapeutic value. The aim of our work
      was to assess the therapeutic effect of the Kuhlmann method in the treatment of
      advanced stages of Kienbock's disease. MATERIAL: From January 1996, eighteen
      patients (18 wrists) diagnosed with Kienbock's disease were operated on, using
      the Kuhlmann method, and the group of these patients was included in this follow
      up study. The average follow-up time was 7.6 +/- 2.3 years. METHODS: The results
      were evaluated on the basis of subjective (VAS) and functional criteria (ROM,
      grip force, DASH questionnaire and combined Cooney score questionnaires) and
      radiological assessment (arthritis evaluation, C.H.I., Natrass index, RSA).
      RESULTS: All patients experienced pain relief. The average pain assessment by VAS
      (10-point scale) before and after the procedure was 8.76 +/- 0.9 and 2.94 +/-
      1.59, respectively. The range of motion was reduced on the operated extremity
      (70% compared to non-operated) as well as the grip test (57%). The average DASH
      score at the time of study was 20.9 +/- 12.2 and the average Cooney score was
      67.6 +/- 17.4. Before the operation, eleven wrists showed signs of
      osteoarthritis. At the follow-up evaluation, arthritis was present in fifteen
      patients.We found a significant difference in average radiological parameters
      characterizing a carpal collapse deformity (C.H.I., Natrass index, RSA) - all
      parameters showed deteriorating tendencies. DISCUSSION: In nine patients,
      necrotic changes of the lunate occurred. In the patients whose pisiforme was not
      affected, a moderate retardation of carpal collapse occurred. However, the
      discrepancy between relevant indicators (C.H.I, Natrass index, RSA) was not
      statistically significant when comparing both groups. Therefore, we cannot
      conclude as to whether or not a vital transposed pisiforme bone impedes the
      development of carpal collapse. The only proved difference between these two
      groups was in pain evaluation, measured by VAS, after the procedure CONCLUSION:
      Although there was a good subjective assessment of the operation results, we are
      of the opinion that this method should not be used as a routine surgical
      procedure for advanced Kienbock disease. In view of a large number of failed
      cases we believe that this method should be considered very carefully.

PMID- 19755057
TI  - [Osteosynthesis of intracapsular femoral neck fractures by dynamic hip screw
      (DHS) fixation].
AB  - PURPOSE OF THE STUDY: The treatment of femoral neck fractures shows a relatively
      high number of poor outcomes, usually due to late complications, such as
      avascular necrosis of the femoral head or pseudoarthrosis. The latter may develop
      when the osteosynthesis of osteoporotic bone fails. The aim of this retrospective
      study was to evaluate a group of patients treated by osteo- synthesis for intra
      capsular femoral neck fractures at our department, and to verify indication
      criteria and identify the therapeutic procedures that are best suited to our
      conditions. MATERIAL: In the 1997-2001 period, a total of 81 patients with intra
      capsular femoral neck fractures were operated on. Of these, 64 treated by dynamic
      hip screw (DHS) fixation were followed up for at least 5 years. There were 33
      women and 31 men; the average age was 21.5 years (range, 21 to 74 years).
      METHODS: The Garden classification was used to evaluate the displacement of
      femoral neck fractures. Preferably, osteosynthesis was carried out by closed
      reduction; only exceptionally was an extension device for the operating table
      used. A 135-degree sliding hip screw, with a short thread, directed to the head
      centre and a two-hole side plate were used most often.The average follow-up was
      6.9 years. Evaluated were: the occurrence of late complications in relation to
      the length of time between injury and surgery, quality of fracture reduction, use
      of an anti-rotation screw and necessity of repeat surgery. RESULTS: Garden I or
      II fractures were diagnosed in 13 patients, 51 had Garden III or Garden IV
      fractures. Bone union without complications was achieved in 73.4 % of the
      patients within 12 months of surgery. Late complications were found in 26.6 %; of
      these, only one had Garden I fracture and the rest were Garden III and IV
      fractures. An anti-rotation screw was used in 39 patients (60.9 %) and its use
      had no effect on the development of late complications. Of the seven patients who
      developed pseudoarthrosis, the screw was used in four (57.1%); out of the nine
      patients with avascular necrosis, it was used in six (66.7 %). In the whole
      group, an unsatisfactory outcome of post-operative reduction was recorded in 29.7
      %. In the patients with late complications this was found in 52.9 %, which was a
      statistically significant difference. Of the 17 patients with poor outcomes, 14
      underwent total hip arthroplasty; in the patients with necrosis, arthroplasty was
      carried out at an average of 26 months post-operatively, in those with
      pseudoarthrosis it was at 7 months post-operatively. DISCUSSION: For the
      treatment of intra-capsular fractures of the femoral neck, surgery is the most
      frequent approach, but there are controversial views on various relevant issues.
      An important factor affecting the treatment outcome is the patient's bone
      quality. CONCLUSIONS: Our results show a direct relationship between the extent
      of fracture displacement and late complications, i.e., avascular necrosis and non
      union. The quality of fracture reduction had a greater effect on fracture non
      union than on the development of femoral head necrosis. The length of time
      between injury and surgery played a lesser role than it is believed. The use of
      an anti-rotation screw was not significantly related to the occurrence of late
      complications. The DHS method is economical and available, and provided
      sufficient results whose comparisons with the literature data show that this
      therapeutic approach is correct.

PMID- 19755058
TI  - [Arthrodesis of the carpometacarpal joint of the thumb using a cannulated screw].
AB  - PURPOSE OF THE STUDY: To present the results of surgical treatment of
      carpometacarpal joint arthritis of the thumb, using cannulated screw fixation
      which is stable and, after bony union, allows the patient to do also harder
      manual work MATERIAL: In the years 2000 to 2005, this method was used for 20
      operations in 18 patients (16 women and two men); one man and one woman had
      bilateral surgery. The right hand was operated on in seven cases and the left one
      in 13 cases. The average age of the patients was 61 years. METHODS: The procedure
      was performed from the dorsoradial approach, access to the joint was gained
      between the extensor pollicis brevis and abductor pollicis longus tendons, and
      care was taken to protect the superficial branch of the radial nerve. The
      articular surface of the trapezium bone and the first metacarpal base including
      osteophytes were resected and arthrodesis was carried out by means of a 4.5 mm
      cannulated screw. The final position of the thumb axis was at 40 degrees to 45
      degrees palmar abduction, 20 degrees to 25 degrees extension and 10 degrees to 15
      degrees pronation. A plaster hand splint was applied for 6 to 8 weeks post-
      operatively. The patients were capable of full use of the hand at 3 months after
      surgery. RESULTS: Evaluation included a pain scale of 1 to 5 grades, range of
      motion, reduction of muscle strength and fine motor function. All operative
      wounds healed by first intention, no infection or neurological complications were
      recorded. Primary union was achieved in 18 cases, two developed pseudoarthrosis.
      The patients reported improvement on the pain scale by 2 grades on average.
      However, in thumb opposition tasks, the range between the tip of the thumb and
      the fifth metacarpophalangeal joint decreased on average by 20 mm. Fourteen
      patients reported deterioration of fine motor function. All patients were
      satisfied with improved muscle strength enabling them to do more demanding
      physical work. DISCUSSION: The results of carpometacarpal joint arthrodesis by
      means of a cannulated screw are comparable with those of arthrodesis using other
      implants. The final thumb position is discussed as well as the use of suitable
      fixation material in order to prevent pseudoarthrosis. Issues such as the use of
      interpositioned tissue, shortening of the radial column and the resultant limited
      muscle strength in resection arthroplasty, and the choice of a most suitable
      implant and possibility of its failure in alloplasty are also discussed.
      CONCLUSIONS: Arthrodesis with cannulated screw fixation is best for treatment of
      the carpometacarpal joint of the thumb with stage III rhizarthritis (Eaton
      classification). It results in an axis-stable thumb that is pain free and capable
      of physical activity and firm grip.

PMID- 19755059
TI  - [Ipsilateral traumatic dislocation of hip and knee joints. Case report].
AB  - Traumatic obturator dislocation of the hip without fracture associated with
      antero-lateral knee dislocation is considered to be an extreme injury. Such a
      case, which has never been treated in our department, is reported here. The
      patient was a 40-year-old man who suffered his injury in a motorcycle accident.
      He had ipsilateral traumatic obturator hip dislocation and anterior knee
      dislocation.Within two hours of injury dislocation reduction was carried out
      under general anaesthesia, the anterior cruciate ligament was reconstructed using
      BTB allograft and a CT scan was obtained. In this type of trauma CT-angiography
      is always indicated to detect any possible threat to limb vitality. The
      functional results were excellent and were directly dependent on the correct use
      of arthroscopy. At 3 years post-operatively, his hip and knee joints were
      examined. The Harris hip score was 98 points and the International Knee
      Documentation Score (IKDC) was also excellent. There was no neurological deficit,
      although this type of trauma is usually associated with neurological
      complications. At the time of examination the patient was symptom free.

PMID- 19755060
TI  - [Post-traumatic hypoglossal nerve paresis due to occipital condyle fracture].
AB  - The authors describe the case of a patient, a 33-year-old man, who presented with
      paresis of the hypoglossal nerve following an occipital condyle fracture. The
      patient, as a driver, was involved in a car accident and from the beginning he
      complained of neck pain. The diagnosis was established by CT examination as late
      as 72 hours after injury on the basis of clinical presentation (difficulty in
      swallowing, chewing and speaking due to impaired mobility of the left half of the
      tongue, with the left half showing a marked hypotrophy and muscle weakness). A
      conservative treatment was used - application of a rigid cervical collar for 3
      months, which resulted in gradual neurological improvement.

PMID- 19755061
TI  - [Geriatric traumatology - vision or reality?].
AB  - The aim of the paper is to provide information on the establishment of the
      Geriatric Fracture Centre (GFC) at the Department of Orthopaedics and
      Traumatology, Faculty Hospital at the Faculty of Medicine, Charles University,
      Pilsner, whose goals and services are in accordance with the principles of the
      Rochester GFC, USA, and the AO Foundation at Synthes Inc. The paper presents up
      to-date information on the methods of osteosynthesis for the skeletal system
      affected by osteoporosis, the majority of which was obtained in the AO Geriatric
      Fracture Course in Davos, December 2007. The authors are concerned with the pre
      operative examination of geriatric patients who suffered a fracture.The
      anaesthesiologist's view on our elderly patients, their pre-operative
      preparation, anaesthesia application and post-operative care are presented.The
      novel method of two-phase bone densitometry and its role in the therapy of
      osteoporosis for elderly patients with fractures are also mentioned.

PMID- 19755062
TI  - Incoming Presidential Address and New 2009 AOFAS Board of Directors.

PMID- 19755063
TI  - Matrix-Induced Autologous Chondrocyte Implantation (MACI) grafting for
      osteochondral lesions of the talus.
AB  - BACKGROUND: Articular cartilage is limited in its ability to repair itself.
      Matrix-induced Autologous Chondrocyte Implantation (MACI) is an established
      treatment method for such articular cartilage defects in the knee. Recently the
      technique has been used in the ankle. We present a series of patients treated
      with MACI for osteochondral defects of the ankle, and assess the functional and
      clinical results. MATERIALS AND METHODS: From August 2003 to February 2006, 20
      patients underwent MACI grafting for osteochondral defects in the ankle. Age
      ranged from 19 to 61 (mean, 36) years. Mean followup was 21.1 months. Clinical
      and functional evaluations were conducted using the AOFAS scoring system.
      RESULTS: The mean size was 233 mm(2). There was a significant improvement in mean
      AOFAS score from 60 (range, 25 to 87) to 87 (range, 41 to 100) (p < 0.0001).
      Overall improvement in pain scores was also significant (p < 0.0001). All
      osteotomies healed. Four patients required hardware removal and two underwent
      arthroscopic debridement for anterior impingement. There were two failures which
      are awaiting subsequent procedures. CONCLUSION: We believe MACI is a reliable
      treatment method for talar osteochondral defects. The method usually requires an
      intra-articular osteotomy, although this proved to be a reasonably simple aspect
      of the procedure for the treatment of cartilage defects of the talus.

PMID- 19755064
TI  - Analysis of retrieved agility total ankle arthroplasty systems.
AB  - BACKGROUND: First generation total ankle arthroplasty (TAA) systems showed high
      rates of failure. The Agility (DePuy, Warsaw, IN) TAA system, a second generation
      design, had improved outcomes; however, implant failure due to loosening of the
      metallic components persisted. The purpose of this study was to analyze the
      damage modes and radiographic mode(s) of failure observed in retrieved Agility
      TAA. MATERIALS AND METHODS: Ten devices were collected and each component was
      analyzed for common damage modes using microscopy. Clinical damage was analyzed
      with postoperative implant and preoperative revision procedure radiographs.
      RESULTS: Analyses revealed damage/wear to retrieved components, including
      abrasion, dishing, and pitting. These third-body wear particles may be a
      precursor to wear debris induced osteolysis which could cause component
      loosening. Seven TAA systems were removed due to loosening or subsidence,
      suggesting component damage/wear may lead to clinically observed component
      loosening. Retrieval analysis indicated the polyethylene experiences edge
      loading, resulting in increased contact stresses to polyethylene in the primary
      articulation region and wear. CONCLUSION: Since poor clinical outcomes have been
      associated with component instability and osteolysis, analyzing retrieved
      components wear and damage may be an important step toward improving implant
      design, thereby decreasing wear debris induced osteolysis and improving clinical
      outcomes.

PMID- 19755065
TI  - Intermediate term outcome of the agility total ankle arthroplasty.
AB  - BACKGROUND: Although ankle arthrodesis provides pain relief and improved
      function, newer generation total ankle arthroplasty designs, with improved
      kinematic properties, have emerged and showed encouraging results. The purpose of
      this study was to review the intermediate term outcome of the Agility Total Ankle
      Arthroplasty prosthesis. MATERIALS AND METHODS: A retrospective review was
      performed on 28 total ankle arthroplasty procedures performed over a period of 5
      years. The American Orthopedic Foot and Ankle Society (AOFAS) questionnaire was
      used for evaluation. Pre-existing medical and surgical conditions that could
      potentially affect outcome were recorded. The mean age at surgery was 68.5 years
      with 39% males and 61% females. RESULTS: The mean AOFAS Ankle-Hindfoot score
      improved significantly from 34.9 to 76.4 (p < 0.001). Pain relief was the main
      factor in improving the score followed by improved function. Complications varied
      from delayed wound healing, wound infection, painful hardware, iatrogenic
      malleolar fracture and arterial injury, to patients requiring free flap coverage.
      Despite the high rate of complications, which were successfully treated, most
      patients were satisfied at the last followup. CONCLUSION: Total ankle
      arthroplasty using the Agility Total Ankle Arthroplasty prosthesis has clinically
      encouraging outcomes; however the high complication rate should prompt surgeons
      to carefully select patients for this procedure.

PMID- 19755066
TI  - Tumors of the foot and ankle: experience with 153 cases.
AB  - BACKGROUND: Both primary and metastatic tumors in the foot and ankle have been
      reported as rare. The purpose of this study was to describe 153 cases of foot and
      ankle tumors from a 20-year experience in a tertiary referral center specializing
      in orthopaedic oncology. It is the largest reported series of both bone and soft
      tissue tumors in the foot and ankle. MATERIALS AND METHODS: Between 1986 and
      2006, a retrospective chart review was performed of a total of 2,660 tumors
      surgically treated in all anatomic sites by a single surgeon at a musculoskeletal
      tumor referral center. RESULTS: One hundred fifty-three patients (5.75%) with
      bone and/or soft tissue tumors of the foot and ankle were treated. There were 84
      women and 69 men. The patients' ages ranged from 1 to 84, with a median age of 30
      and mean of 33.2. The tissue types included 80 soft tissue and 73 bone tumors.
      Overall, 60 (39.2%) were malignant, and 93 (60.8%) were benign. The most common
      diagnosis was giant cell tumor. In addition, giant cell tumor was the most common
      bone tumor, while pigmented villonodular synovitis and giant cell tumor of the
      tendon sheath were the most common soft tissue tumors. CONCLUSION: The incidence
      of tumors of the foot and ankle in this series of a single surgeon over a 20-year
      practice was 5.75%. The results of this study reaffirm that awareness, correctly
      diagnosing, and appropriately treating or referring to an orthopaedic oncologist
      may help with an improved outcome for patients.

PMID- 19755067
TI  - Midfoot ulcers treated with gastrocnemius-soleus recession.
AB  - BACKGROUND: Foot ulcers in patients with neuropathy are a common cause of
      hospital admission for infection sometimes resulting in amputation in patients
      with neuropathy. Tendon lengthening alone has been reported to be successful in
      treating neuropathic forefoot ulcers. Tendon lengthening has also been
      recommended as an adjunct to bony procedures (exostectomy or fusion) for treating
      midfoot ulcers. The author reports the results of gastrocnemius-soleus recession
      as the sole treatment of diabetic midfoot ulcers. MATERIALS AND METHODS: This
      study evaluated the results of 11 patients with 11 neuropathic plantar midfoot
      ulcers who were treated primarily with gastrocnemius-soleus recession with an
      average followup of 39 months. Potentially risky bony procedures were done after
      tendon lengthening if ulcers did not heal or recurred. RESULTS: Ten of the ulcers
      healed but one patient was lost to followup after his ulcer healed. One ulcer did
      not heal and one ulcer recurred but healed again after midfoot fusion. One
      patient later had a transfemoral amputation due to gangrene. Two patients later
      died from medical problems unrelated to their surgery. There were no incision
      problems, or transfer ulcers. CONCLUSION: The author believes gastrocnemius
      soleus recession as a primary treatment of diabetic midfoot ulcers is a low risk
      method of promoting ulcer resolution.

PMID- 19755068
TI  - Management of long-term sequelae of compartment syndrome involving the foot and
      ankle.
AB  - BACKGROUND: Lower leg compartment syndrome can lead to severe sequelae affecting
      patient autonomy. Ischemic muscle fibrosis and retraction result in foot and
      ankle deformities ranging from claw toes to complex multiplanar dislocations with
      soft tissue impairment requiring amputation. Although these deformities have been
      reported in relation to compartment syndrome, they have rarely been discussed
      specifically in the light of a long term follow up. MATERIALS AND METHODS:
      Between 1981 and 2006, 151 patients were treated in our hospital for compartment
      syndrome of the lower limb. Ten of them later required further surgery to treat
      sequelae on the foot and ankle and were followed up prospectively. Personal data
      and surgical events were recorded, as well as potential risk factors for sequelae
      and functional outcome. The data was analyzed and compared to that available in
      previous literature. We analyzed and describe the different surgical procedures
      available for the management of this condition including arthroscopic ankle
      arthrodesis which could be a less invasive and efficient technique in mild
      equinus deformities. RESULTS: All ten patients were diagnosed late for
      compartment syndrome. The anterior and lateral compartments were most often
      involved but rarely accounted for late sequelae. The deep posterior compartment
      seems to be the key element in generating after effects. Functional results were
      good in eight patients. Two required amputation after failed secondary surgery.
      CONCLUSION: The late, post-compartment syndrome affecting the foot and ankle can
      be treated efficiently provided surgery is performed acurately, taking into
      account the multiplanar deformity. However, the best treatment for this condition
      remains prevention.

PMID- 19755069
TI  - Triple nerve block at the knee for foot and ankle surgery performed by the
      surgeon: difficulties and efficiency.
AB  - BACKGROUND: Combined nerve blocks at the knee can provide safe anesthesia below
      the knee avoiding the potential complications of general or spinal anesthesia
      while reducing the need for opioids in the postoperative period. This study
      presents the outcomes of a large series of patients that underwent foot and ankle
      surgery receiving a triple nerve block at the knee. MATERIALS AND METHODS: Three
      hundred eighty patients underwent foot and ankle surgery receiving anesthesia
      with triple nerve block at the knee (tibial, common peroneal and saphenous
      nerve). Surgery included a variety of bone and soft tissue procedures. The nerve
      block was performed by an orthopaedic surgeon in the lateral decubitus position.
      RESULTS: The successful nerve block rate was 91 percent. There was no need to
      convert to general or spinal anesthesia, although 34 patients (9%) needed
      additional analgesia intraoperatively. Complete anesthesia required 25 to 30
      minutes from the time of performing the block. No complication occurred secondary
      to the use of the anesthetic agent (ropivacaine 7.5%). Postoperative analgesia
      lasted from 5 to 12 hours, reducing the need of additional analgesics.
      Hospitalization averaged 1.4 days (from 0 to 5) with the majority of patients
      discharged the day after the operation (248/380). A high satisfaction rate was
      reported by the patients with no adverse effects and complications. CONCLUSION:
      We found triple nerve block at the knee to be a safe and reliable method of
      regional anesthesia providing low morbidity, high success rate, long acting
      analgesia, and fewer complications than general or spinal anesthesia. It is a
      simple method that can be performed by the orthopaedic surgeon.

PMID- 19755070
TI  - Preoperative footbaths reduce bacterial colonization of the foot.
AB  - BACKGROUND: Previous studies have demonstrated higher infection rates following
      elective procedures on the foot and ankle compared with procedures involving
      other areas of the body. Previous studies also have documented the difficulty of
      eliminating bacteria from the forefoot prior to surgery. The purpose of the
      present study was to ascertain if preoperative chlorhexidine bathing decreased
      the number of bacteria on the forefoot. MATERIALS AND METHODS: From October 2005
      to October 2006, a prospective study was undertaken to evaluate 44 consecutive
      patients undergoing planned, elective surgery of the foot and ankle. (mean age,
      43.9 years; range, 17 to 85 years; 25 female, 19 male). Twenty-two patients were
      assigned to each group. They were randomly assigned to have preoperative footbath
      with chlorhexidine gluconate (Hibitane) (Group 1) 20 minutes before surgery or
      placebo (Group 2). Culture swabs were taken from all web spaces, nail folds, toe
      surfaces and proposed surgical incision sites before the preoperative bath,
      during the procedure and immediately after surgery. RESULTS: In Group 1, bacteria
      grew on the intraoperative culture in 60% and 0% of immediate postoperative
      cultures. In Group 2, 96% of intraoperative cultures and 16% of postoperative
      cultures. The difference in the intraoperative bacterial count was statistically
      significant (p = 0.002). The difference in postoperative bacterial counts was
      marginally significant (p = 0.055). No complications were recorded in either
      group. CONCLUSION: These data indicate that chlorhexidine provides better
      reduction in skin flora than placebo. Based of these data, we recommend the use
      of a chlorhexidine footbath in addition to standard surgical preparatory agent
      before foot and ankle surgery.

PMID- 19755071
TI  - Proximal first metatarsal opening wedge osteotomy with a low profile plate.
AB  - BACKGROUND: Many surgical procedures have been described for the correction of
      metatarsus primus varus associated with hallux valgus deformity. The purpose of
      this study was to present the results of the proximal metatarsal opening wedge
      (PMOW) osteotomy using the Arthrex LPS(R) first metatarsal system. MATERIALS AND
      METHODS: Eighty-four patients (90 feet) underwent PMOW osteotomy with distal
      bunionectomy. There were 78 patients (93%) and 84 (93%) feet available for
      followup. Mean followup was 2.4 (range, 2.0 to 3.2) years from the time of the
      index surgery. Pre- and postoperative clinical examination, level of activity,
      patient derived subjective satisfaction score, radiographic measurements, and
      visual analogue scale (VAS) score for pain were obtained and evaluated
      retrospectively. RESULTS: The mean preoperative VAS score was 5.9 (+/- 2.2),
      compared with a mean postoperative score of 0.5 (+/- 0.8). The mean 1-2 IMA
      preoperatively was 14.5 (+/-3.3) degrees, compared with postoperative
      measurements of 4.6 (+/- 2.8) degrees. The mean hallux valgus angle (HVA)
      improved from a mean of 30 (range, 22 to 64) degrees preoperatively to 10 (range,
      -15 to +18) degrees. The mean time to radiographic union was 5.9 (range, 4 to 14)
      weeks. There was one nonunion, one delayed union, mild hallux varus in two
      patients, severe hallux varus in two patients, recurrent hallux valgus in three
      patients (including the nonunion) and no instances of plate failure there was no
      significant difference in mean preoperative (74.8 degrees +/- 11) compared to
      postoperative (67.9 degrees +/- 10) total MTP joint range of motion. Ninety
      percent of patients reported good to excellent subjective results after the index
      surgery. CONCLUSION: We believe PMOW osteotomy was near ideal in terms of
      reliable, predictable correction and healing. Length of the first metatarsal was
      maintained and patients ambulated safely in a CAM walking boot immediately after
      surgery. We believe a first web space release may result in hallux varus and
      increased distal metatarsal articular angle (DMAA) was associated with hallux
      valgus recurrence.

PMID- 19755072
TI  - Radiographic correlation of hallux MP fusion position and plate angle.
AB  - BACKGROUND: This study assessed the variability of plate bend in regard to final
      metatarsophalangeal (MP) fusion angles and toe-to-floor distance. We hypothesized
      that the final MP angle, the angle of the proximal phalanx to the floor, and the
      weightbearing toe-to-floor distance would be dictated solely by the magnitude of
      the bend in the plate. MATERIALS AND METHODS: This is a retrospective analysis of
      35 sequential patients who underwent MP fusion with a low-contour titanium plate.
      Postoperative weightbearing radiographs were analyzed for plate angle, MP fusion
      angle, the angle of the proximal phalanx to the floor, and the weightbearing toe
      to-floor distance. RESULTS: We found statistical correlation between plate angle
      and MP angle and between plate angle and the angle of the proximal phalanx to the
      floor. However, there was low correlation between plate angle and with toe-to
      floor distance. In addition, we noted many outliers, which resulted in higher or
      lower correlation of the MP angle to the expected plate angle and, thus, a
      relationship between angles that was far from linear. CONCLUSION: Care needs to
      be taken when relying solely on the bend in the plate to determine the final
      position of the toe in MP fusions. Although the association between plate bend
      and MP angle and proximal phalanx to floor angle was strong, the association
      between the bend in the plate and weight bearing toe-to-floor distance was
      variable. This could result in the toe hitting the shoe or the need to vault over
      the toe. Therefore, the surgeon must match the plate to each patient's anatomy to
      ensure proper weight bearing toe-to-floor distance and not rely on plate angle
      exclusively.

PMID- 19755073
TI  - Effect of eccentric exercise program for early tibialis posterior tendinopathy.
AB  - BACKGROUND: Morphology and vascularization of painful tibialis posterior (TP)
      tendons before and after an intervention targeting the degenerated tendon were
      examined. Functional status and pain level were also assessed. MATERIALS AND
      METHODS: A10-week twice daily, progressive eccentric tendon loading, calf
      stretching program with orthoses was implemented with ten, early stage TP
      tendinopathy subjects. TP tendons were imaged by grayscale and Doppler ultrasound
      at INITIAL and POST evaluations to assess the tendon's morphology and signs of
      neovascularization. The Foot Functional Index (FFI), Physical Activity Scale
      (PAS), 5-Minute Walk Test, and single heel raise (SHR) test were completed at
      INITIAL and POST evaluations. The Global Rating Scale (GRS) was completed at 6
      months followup. One-way ANOVA was used to compare the FFI at INITIAL, POST, and
      6-MONTH time points. Paired t-tests were used to compare means between the
      remaining variables. The level of significance was p = 0.05. RESULTS: There was a
      significant difference in FFI total, pain, and disability at the three time
      points. Post-hoc paired t-tests revealed that the FFI scores were lower for the
      total score and pain and disability subcategories when comparing from INITIAL to
      POST and INITIAL to 6-MONTH evaluations (p < 0.05 for all). The number of SHR
      increased significantly on the involved side from INITIAL to POST evaluation (p =
      0.041). The GRS demonstrated minimum clinically important differences for
      improvements in symptoms at 6-MONTH. Tendon morphology and vascularization
      remained abnormal following the intervention. CONCLUSION: A 10-week tendon
      specific eccentric program resulted in improvements in symptoms and function
      without changes in tendon morphology or neovascularization.

PMID- 19755074
TI  - Ultrasound guidance for intra-articular injections of the foot and ankle.
AB  - BACKGROUND: Ultrasound has been increasingly utilized in procedures involving
      intra-articular injections. This study's purpose was to compare the accuracy of
      intra-articular injections of the foot and ankle using palpation versus dynamic
      ultrasound in a cadaver model. MATERIALS AND METHODS: Fourteen lightly embalmed
      cadaver specimens without notable osteoarthritis were used. A 0.22-gauge needle
      was placed by a foot and ankle orthopaedic surgeon into the first and second
      tarsometatarsal joints, subtalar joint, and ankle joint. The needle was initially
      placed using palpation, evaluated with ultrasound by an experienced
      rheumatologist, and re-inserted if necessary. Needle placement was confirmed with
      injection of an Omnipaque/methylene blue solution and examined under fluoroscopy,
      followed by dissection. RESULTS: Palpation and ultrasound were 100% accurate in
      subtalar and ankle joint injections. Using palpation, the needle was correctly
      placed into the first TMT joint in three of 14 cadavers, and in four of 14
      cadavers for the second TMT joint. Using ultrasound, the needle was correctly
      placed into the first TMT joint in ten of 14 cadavers, and into the second TMT
      joint in eight of 14 cadavers. When grouped, ultrasound was significantly more
      accurate for intra-articular needle placement compared to palpation in the
      midfoot (p = 0.003). On three specimens, dye extended beyond the second TMT
      joint. CONCLUSION: Intra-articular injections of the subtalar and ankle joints
      can be successfully performed utilizing palpation alone. Ultrasound guidance
      significantly increases injection accuracy into the TMT joints compared to
      palpation alone and therefore US or Fluoroscopy is performed when injecting these
      TMT joints. When using selective diagnostic injections into a TMT joint to assess
      for the symptomatic joint and potential need for arthrodesis, the injected
      anesthetic may not remain isolated within that joint. These isolated TMT
      injections should not be done to answer that question without fluoroscopy
      confirmation with radiopaue dye demonstrating the injected fluid remained within
      the one joint of interest.

PMID- 19755075
TI  - Midfoot charcot arthropathy with improvement of arch after achilles tendon
      lengthening: a case report.

PMID- 19755076
TI  - Using the bi-masquelet technique and reamer-irrigator-aspirator for post
      traumatic foot reconstruction.

PMID- 19755077
TI  - Treatment of a distal tibial osteochondral lesion with a synthetic osteochondral
      plug: a case report.

PMID- 19755078
TI  - Surgical strategies: use of the cuboid osteotomy in combination with the triple
      arthrodesis with lateral column overload.

PMID- 19755079
TI  - Rare case of a broken toothbrush as a parapharyngeal space foreign body.

PMID- 19755080
TI  - Approaches to the wide nasal tip (case-based application).

PMID- 19755081
TI  - Ex vivo tracheal mucociliary clearance in rats: comparisons of nebulization
      versus irrigation with lactated Ringer and saline solutions.
AB  - OBJECTIVE: This study was performed to compare the effects of isotonic saline,
      hypertonic saline (buffered/nonbuffered), and lactated Ringer irrigation and
      distilled water nebulization on mucociliary clearance in ex vivo rats. DESIGN:
      Experimental study. SETTING: Tertiary otolaryngology care centre. METHODS: Thirty
      rat tracheas were achieved from 15 rats by dividing the trachea longitudinally
      into two equal parts. MAIN OUTCOME MEASURES: Mucociliary transport velocity was
      measured by direct observation of particle placed on the lower end of the trachea
      after irrigation or nebulization. RESULTS: Significant improvement in mucociliary
      clearance was found with isotonic saline (p = .002), buffered hypertonic saline
      (p = .018), lactated Ringer (p = .000), and nebulized distilled water (p = .000)
      when compared with nonbuffered hypertonic saline. CONCLUSION: Lactated Ringer
      solution is better than saline solution at enhancing mucociliary clearance, but
      nebulized distilled water is superior to the tested irrigation solutions in rat
      tracheal epithelium.

PMID- 19755082
TI  - Steel scalpel versus electrocautery blade: comparison of cosmetic and patient
      satisfaction outcomes of different incision methods.
AB  - OBJECTIVE: To determine which method of skin incision has superior cosmetic and
      patient satisfaction outcomes. METHODS: Consenting patients undergoing bilateral
      neck dissection who met the inclusion criteria were prospectively enrolled. Each
      side of the neck was randomly assigned into one of the following two groups:
      scalpel incision and electrocautery incision. Cosmetic and patient satisfaction
      outcomes were collected prospectively with patients and outcome assessors blinded
      to group assignment. Validated self-report questionnaires and objective scar
      measures were used. RESULTS: Nineteen patients met the criteria for inclusion.
      Analysis revealed no significant differences between groups in terms of cosmetic
      or satisfaction outcomes. Use of the steel scalpel was found to result in
      significantly greater incision-related blood loss compared with use of the
      electrocautery blade. CONCLUSION: Steel scalpel or electrocautery may be used to
      incise the skin of patients undergoing bilateral neck dissection with no
      difference in cosmetic or patient satisfaction outcome. The steel scalpel yields
      greater incision-related blood loss compared with the electrocautery blade.

PMID- 19755083
TI  - Radiotherapy for T1 and T2 laryngeal cancer: the Dalhousie University experience.
AB  - OBJECTIVE: To report outcomes of definitive radiotherapy for early-stage squamous
      cell carcinoma of the larynx. DESIGN: Retrospective outcome analysis. SETTING:
      Tertiary referral centre. PATIENTS AND METHODS: A total of 373 cases of laryngeal
      cancer reported in Nova Scotia from 1990 through 2001 were reviewed. All cases
      were classified by T stage (T1 = 137, T2 = 90, T3 = 89, T4 = 57) and affected
      sites (glottic = 233, supraglottic = 136, subglottic = 4). We focused on those
      patients with T1 and T2 cancers of both the glottis and the supraglottis who
      received radiotherapy as a primary modality. RESULTS: Eighty-eight percent (150
      of 170) of T1/T2 glottic cancers were first treated with radiotherapy. Seventy
      one percent (80 of 112) and 63.3% (24 of 38) of T1 and T2 glottic cancers,
      respectively, were controlled by radiation, with an average follow-up of 37
      months. Of those T1 glottic cancers unsuccessfully treated by radiotherapy, 14
      underwent surgical salvage, with 9 of these patients being free of disease
      following an average of 57 months. For T2 glottic cancers unsuccessfully treated
      by radiotherapy, five patients underwent surgical salvage, of whom four (68.4%)
      were free of disease after an average follow-up of 62 months. Seventy-five
      percent of T1 (3 of 4) and 70.6% (25 of 35) of T2 supraglottic cancers were
      successfully controlled by radiotherapy. Salvage surgery was attempted in five
      patients; however, all patients except one died of disease. CONCLUSION: Although
      radiotherapy is a standard treatment for early laryngeal cancers, the results of
      this review may suggest considering other modalities in the treatment of early
      laryngeal cancer.

PMID- 19755084
TI  - Reverse multidrug resistance in laryngeal cancer cells by knockdown MDR1 gene
      expression.
AB  - BACKGROUND: Resistance to chemotherapeutic agents is one of the major obstacles
      in the treatment of laryngeal cancer. Upregulated expression of P-glycoprotein
      (Pgp), the MDR1 gene product, confers multidrug resistance (MDR) to laryngeal
      cancer cells. In this study, we reversed the resistance to chemotherapeutic
      agents in human laryngeal cancer cells (LSC-1/TAX) by using the lentivirus-based
      small hairpin interference ribonucleic acid (shRNA) technique. METHODS: LSC-1/TAX
      cells were transfected with lentivirus vector that contains the shRNA construct
      targeting MDR1 messenger ribonucleic acid (mRNA). The knockdown of MDR1 gene
      expression was assessed by reverse transcription polymerase chain reaction (RT
      PCR), and the protein level of Pgp was determined by Western blot and
      immunocytochemistry. Sensitization of the laryngeal cancer cells to various
      antineoplasm agents will be quantified by methylthiazolyl tetrazolium (MTT)
      assays. Apoptosis was analyzed by flow cytometry. RESULTS: It was shown that MDR1
      shRNA transfection reduced the MDR1 gene expression in LSC-1/TAX cells by RT-PCR
      experiment. Western blot and immunocytochemistry showed that Pgp expression was
      significantly and specifically inhibited. MTT assay revealed a reverse of MDR1
      gene-dependent MDR in the laryngeal cancer cells using shRNA lentivirus vectors.
      Increased apoptosis has been observed in the MDR1 knockdown LSC-1/TAX cells when
      exposed to paclitaxel (TAX) treatment. CONCLUSIONS: MDR1 shRNA lentivirus vectors
      can significantly inhibit MDR1 expression at both mRNA and protein levels.
      Inhibition of MDR1 gene expression conferred an increased sensitivity to drug
      resistance in laryngeal cancer cells to conventional chemotherapeutic agents.

PMID- 19755085
TI  - Influence of previous tumours on survival in early (Tis-T1) glottic carcinoma.
AB  - OBJECTIVE: To investigate the influence of previous tumours on overall survival
      in patients with early glottic carcinoma. DESIGN: Retrospective, population-based
      cohort study. SETTING: Cancer registration area in the west Netherlands. METHODS:
      Population-based data on previous and subsequent tumours in patients diagnosed
      with early glottic carcinoma (Tis and T1) in the west Netherlands between 1982
      and 1993 were collected from charts and cancer registries. The impact of previous
      tumours on survival was tested in multivariate analysis. MAIN OUTCOME MEASURES:
      Overall survival. RESULTS: Of 359 patients, 22 patients (6%) had a total of 23
      previous tumours. Previous tumours had an independent impact on overall survival
      (hazard ratio 3.4, p < or = .001). Other determinants of survival were age and
      subsequent tumours. Nonmalignant comorbidity was of borderline significance.
      CONCLUSIONS: Previous tumors have an impact on survival in patients with early
      glottic carcinoma and should be considered as an additional factor in counseling
      and prognostication.

PMID- 19755086
TI  - Comparison of a eustachian barotubometer with a tympanometer to evaluate
      eustachian tube function in chronic suppurative otitis media.
AB  - OBJECTIVE: To compare the eustachian tube function results of a eustachian
      barotubometer with those of a tympanometer in the dry and quiescent stages of
      tubotympanic chronic suppurative otitis media. This study was undertaken to find
      a simple, reliable, and inexpensive alternative to the conventional tympanometer
      that is used on a perforated ear drum. DESIGN: Prospective cross-sectional study
      of 1 year's duration. SETTING: Otolaryngology outpatient clinic of a tertiary
      referral centre. METHODS: A forced opening test and a physiologic opening test of
      the eustachian tube were performed on 31 ears with quiescent tubotympanic chronic
      suppurative otitis media and 38 ears with dry tubotympanic chronic suppurative
      otitis media selected at random. Both tests were performed by two separate
      observers using a eustachian barotubometer first and then the tympanometer in
      perforated mode. MAIN OUTCOME MEASURES: Forced opening response and physiologic
      opening response of the eustachian tube. RESULTS AND OBSERVATIONS: Contingency
      tables (2 x 2) were drawn using the findings of the tests on the two instruments
      separately for the forced opening test and the physiologic opening test. For the
      former test, the sensitivity was 100%, specificity was 20%, validity was 94.20%,
      and positive likelihood ratio was 1.25. For the latter test, the sensitivity was
      96.87%, specificity was 60%, validity was 94.20%, and positive likelihood ratio
      was 2.42. CONCLUSION: The eustachian barotubometer is a simple, reliable, and
      inexpensive alternative for preoperative screening of eustachian tube function in
      the dry and quiescent stages of tubotympanic chronic suppurative otitis media.

PMID- 19755087
TI  - Test-retest reliability of p13n23 and n34p44 components of vestibular evoked
      myogenic potentials in a large healthy population.
AB  - OBJECTIVE: The aim of this study is to evaluate the reliability of the VEMP
      characteristics recorded in a large number of healthy subjects. METHODS: VEMP
      response was obtained on 75 healthy volunteers. Thirty-nine (39) of them were
      males and 36 were females. Their age varied between 25 and 63 years (mean value
      43). Recording was achieved using monaural acoustic stimulation and ipsilateral
      muscle contraction. Latencies of p13, n23, n34, p44 peaks, p13n23 and n34p44
      amplitudes and the interaural amplitude differences (IAD) were assessed. RESULTS:
      The stability of latencies, amplitudes of the first p12-n23 and second n34-p44
      waveforms was verified. The second complex was present in 76%. No factor
      indicates statistically significant side difference for both runs. IAD variable
      was not statistically different from zero in all cases. Results show very good
      reliability for amplitudes, good for some latencies, poor for some other
      latencies and IAD34-44 and very poor for IAD13-23. No strong and significant
      correlations were also found between IAD34-44 and IAD13-23 and between p13n23 and
      n34p44 amplitudes. CONCLUSION: It is the first time that optimal latencies and
      amplitudes for early and late components of VEMP are described in a large sample
      of healthy subjects. The p13, n23, n34 and p44 latencies and p13-n23, and n34-p44
      amplitudes were reliable, verifying that the method is reproducible and feasible.
      The IAD13-23 has the disadvantage of low reliability.

PMID- 19755088
TI  - Survival when treating adenoid cystic carcinoma of the external auditory canal:
      quantitative assessment of case reports.
AB  - BACKGROUND: Adenoid cystic carcinoma (ACC) of the external auditory canal is a
      rare neoplastic condition. The purpose of this study was to conduct a
      quantitative review of case reports to assess the efficacy of treatment options
      and assess prognostic factors. METHODS: Cases were identified using PubMed.
      Kaplan-Meier curves were used to plot overall and disease-free survival. The log
      rank test was used to compare survival curves in the univariate analysis for
      perineural invasion, margin status, and specific treatment modalities. A Cox
      proportional hazard model was used for multivariate analysis. RESULTS: Sixty-six
      cases were identified. The univariate analysis suggests an increased overall (p =
      .03) and disease-free (p = .03) survival for those treated with parotidectomies,
      whereas temporal bone resection decreased survival (p = .07). There was no
      overall or disease-free survival advantage using radiation (p = .8). Positive
      margins decreased both overall (p = .05) and disease-free survival (p = .02).
      Perineural invasion was not significant. The multivariate analysis confirmed the
      findings for parotidectomies (p = .02) and temporal bone resections (p = .01).
      CONCLUSIONS: Although the short-term survival for ACC is high, the risk of
      metastasis and poor long-term survival is high. In addition to local excision
      with negative margins, the surgeon should perform a parotidectomy.

PMID- 19755089
TI  - Comparative analysis of middle ear immune response and micronutrient level
      between mucoid and purulent otitis media.
AB  - OBJECTIVE: To determine the differences in the outcome of treatment, the middle
      ear immune response, and micronutrient status between patients with purulent
      (POM) and mucoid (MOM) otitis media. DESIGN: Children with acute otitis media
      were recruited, treated, and followed up for between 6 and 10 months. The sera
      and middle ear secretion (MES) were analyzed for immunoglobulins and zinc using
      enzyme-linked immunoassay and flame atomic absorption spectrophotometry,
      respectively. The parameters were compared with selected healthy controls.
      SUBJECTS: There were 399 participants: 228 children with acute otitis media
      selected using the American Academy of Otolaryngology-Head and Neck Surgery
      criteria and 171 healthy controls, with ages ranging between 6 months and 9 years
      (mean 7 years; SD 2.32 years). RESULT: POM accounted for 126 of 228 patients, and
      MOM accounted for 102. The chronicity of otitis media (using the 3-month duration
      cutoff) was seen in 87 subjects (46%): 31 of 126 POM subjects and 56 of 102 MOM
      subjects (p = .002). The serum IgA to IgG ratios were 0.03 and 0.07 among POM and
      MOM, respectively; however, the MES IgA to IgG ratios were higher, 0.3 and 0.2,
      for POM and MOM, respectively. This gives a MES to serum ratio of IgA to IgG
      value of 0.3 to 0.03 (10) for POM and 0.2 to 0.07 (2.67) for MOM, which showed a
      significant statistical difference (p = .001). The MES to serum ratios of IgE
      were 0.89 and 1.3 among POM and MOM, respectively (p = .03). There was a
      significant difference in the serum IgG (p = .019), serum zinc (p = .009), and
      MES IgA (p = .028) and IgG (p = .01). CONCLUSION: Chronicity was greater in MOM
      than in POM; POM had a higher middle ear immune response (measured by the MES to
      serum ratio of IgA to IgG) and serum zinc than MOM but a lower MES IgE.

PMID- 19755090
TI  - Toward the development of evidence-based guidelines for the management of
      methicillin-resistant Staphylococcus aureus otitis.
AB  - OBJECTIVES: (1) To determine the causative bacteriology of discharging ears in a
      case series from a tertiary/quaternary academic centre serving an urban
      population and from a review of the literature and (2) to develop treatment
      guidelines for methicillin-resistant Staphylococcus aureus (MRSA) otorrhea based
      on the best available evidence. METHODS: A retrospective analysis of all "ear"
      cultures from the microbiology laboratory at St. Paul's Hospital, Vancouver, was
      performed to ascertain a qualitative analysis on the susceptibility and
      bacteriology data. A systematic review of the literature was performed for all
      studies examining the bacteriology, susceptibility, and treatment for any MRSA
      infection producing otorrhea. RESULTS: Staphylococcus aureus and Pseudomonas
      aeruginosa (PA) were present in 39.7% and 13.5%, respectively, of ear cultures
      obtained at our institution versus 9.9 to 54.1% and 25.0 to 48.6% in identified
      studies in the literature. Methicillin-sensitive Staphylococcus aureus (MSSA) was
      present more frequently than MRSA (31.2% vs 8.5% at our institution; 16.9% vs
      6.9% in the literature). MRSA isolates were often resistant to gentamicin (14.8%)
      and ciprofloxacin (7.7%) but susceptible to trimethoprim-sulfamethoxazole (TMP
      SMX) (85.3%) and fusidic acid (96.3%), suggesting a preponderance of the
      "community strain" of MRSA. CONCLUSION: The susceptibility of MRSA to antibiotics
      in commonly used otic drops (ie, gentamicin and ciprofloxacin) is low. Based on
      the available data, we suggest an evidence-based approach to the management of
      MRSA otorrhea considering whether the strain is community or hospital acquired
      and whether the tympanic membrane is intact.

PMID- 19755091
TI  - Prospective randomized trial to determine whether inhalational anesthetics have
      any effects on hearing function.
AB  - OBJECTIVE: The purpose of this study was to investigate and compare the effects
      of inhalation anesthetics (sevoflurane and isoflurane) on hearing function by
      using an audiometric test battery. DESIGN: A prospective, randomized, double
      blind, clinical trial. SETTING: University hospital. PATIENTS: Fifty-three adult
      patients (American Society of Anesthesiologists I-II) scheduled for sinonasal
      surgery with intratracheal general anesthesia were enrolled in the study. The
      patients were premedicated with diazepam intramuscularly. Propofol 2 mg/kg
      (Diprivan, AstraZeneca, Wilmington, DE) was given intravenously (i.v.) for
      induction of general anesthesia. After endotracheal intubation with vecuronium
      i.v. (1 mg/kg), in group 1 (n = 27) sevoflurane 2% and in group 2 (n = 26)
      isoflurane 1.2% were used to maintain general anesthesia. All patients received
      nitrous oxide during maintenance. MAIN OUTCOME MEASURES: The patients' hearing
      function was measured before anesthesia and 24 hours after surgery by means of
      pure-tone audiometry, high-frequency pure-tone audiometry, and transient evoked
      otoacoustic emissions (TEOAEs) by the same clinician. RESULTS: There were no
      statistically significant differences between the demographic data and the
      hemodynamic and respiratory parameters of the groups. No significant differences
      were found between groups in hearing thresholds of conventional pure-tone
      audiometry and extended high frequency (p > .05). For TEOAE responses, no
      statistically significant differences were determined between pre- and
      postoperative measurements (p > .05). CONCLUSION: It was audiometrically
      demonstrated that general anesthesia did not affect the hearing function in any
      of the patients undergoing sinonasal surgery. These findings encourage the use of
      sevoflurane or isoflurane as a safe agent without any ototoxic effects in
      otorhinolaryngologic surgery with general anesthesia.

PMID- 19755092
TI  - Excisional technique for intradermal nevi of the external auditory canal.

PMID- 19755093
TI  - Endoscopic sinus surgery for medial orbital subperiosteal abscess in children.
AB  - OBJECTIVE: To present our experience with endoscopically managed medial orbital
      subperiosteal abscess (MOSA) in children and to compare the results with external
      drainage of the abscess. METHODS: A retrospective record review was conducted on
      22 children with MOSA, of whom 6 underwent drainage by endoscopic sinus surgery
      (group 1) and 16 underwent external ethmoidectomy (group 2). MOSA was diagnosed
      by computed tomography of the orbits. RESULTS: There were no postoperative
      sequelae in children treated endoscopically, in contrast to facial scarring,
      delayed healing, stitch abscess, unresolved diplopia, or recurrent periorbital
      cellulitis with or without subperiosteal abscess following external drainage.
      Streptococcus pneumoniae and Haemophilus influenzae were isolated in three
      children and one child in group 1, respectively, whereas the cultures were
      negative in the other two group 1 children who received antibiotics prior to
      admission. Streptococcus species were also the most common isolates in group 2
      (50%), followed by H. influenzae (19%). The mean duration of postoperative
      healing was 4.2 +/- 1.9 days (range 2-7 days) in group 1 and 8.6 +/- 4.2 days
      (range 5-17) in group 2 (p = .005). The mean respective hospital stay was 6.0 +/-
      2.0 days (range 4-9 days) and 9.9 +/- 4.2 days (range 5-18 days) (p = .02). One
      group 2 child with residual disease underwent revision external ethmoidectomy 5
      weeks after the initial procedure. Recurrent periorbital cellulitis was
      successfully managed conservatively in two group 2 children, 3 and 10 months
      postoperatively in one child, and 3 months and 6 years postoperatively in the
      other. CONCLUSION: We recommend exclusive use of an endoscopic approach for
      treating MOSA and saving external ethmoidectomy for drainage of superior orbital
      abscesses.

PMID- 19755094
TI  - Endoscopic repair of skull base defects presenting with pneumocephalus.
AB  - OBJECTIVE: Persistent pneumocephalus often indicates the presence of a skull base
      (SB) defect associated with one of the paranasal sinuses. Such defects require
      treatment to avoid sequelae. The study objective was to evaluate success in
      endoscopic closure of SB defects associated with pneumocephalus. DESIGN:
      Retrospective medical record review. SETTING: Tertiary care academic rhinology
      practice. METHODS: A 5-year retrospective review of patients presenting with
      pneumocephalus. Presenting symptoms, etiology of SB defects, radiologic findings,
      operative techniques, and follow-up were evaluated. MAIN OUTCOME MEASURES:
      Success of endoscopic SB defect repair in the setting of pneumocephalus was
      assessed. Factors potentially contributing to failure were evaluated in
      appropriate cases. RESULTS: Eleven patients with pneumocephalus from 14 SB
      defects underwent 17 endoscopic repairs. In 11 surgical procedures, active
      cerebrospinal fluid (CSF) leaks were identified, but in the remaining 6,
      pneumocephalus was present without CSF leak. Radiologic location of
      pneumocephalus ranged from extra-axial to diffuse within the brain parenchyma. SB
      defects were identified using fine-cut computed tomographic (CT) scans, CT
      cisternograms, and intrathecal fluorescein. Defects were located in the sphenoid,
      sella, ethmoid roof, and frontal sinus posterior table. Eight of 11 patients
      (72%) were managed with endoscopic repair alone. Factors potentially affecting
      failure included malignancy, previous radiation, intracranial infection,
      malnutrition, and Cushing disease. CONCLUSIONS: Endoscopic SB defect repair for
      pneumocephalus is largely successful. Localization of SB defects in these cases
      is often assisted by CT cisternography and intrathecal fluorescein.

PMID- 19755095
TI  - Use of alternative medicine in Israeli chronic rhinosinusitis patients.
AB  - OBJECTIVE: The worldwide interest in the use of complementary and alternative
      medicine (CAM) has been established in multiple surveys. Chronic rhinosinusitis
      (CRS) is often an unremitting disease with frequent troubling relapses, and
      despite wide use of endoscopic sinus surgery, conventional medicine may have a
      smaller contribution than expected. Because of prevalent use of CAM among
      patients, it is important that physicians acquire basic knowledge of this
      subject. We studied the prevalence of CAM use among CRS patients in Israel.
      DESIGN: Use of CAM was evaluated in a cohort of consecutive adult patients with
      CRS. SETTING: An outpatient clinic in a tertiary medical centre. METHODS:
      Patients were asked to fill out an anonymous questionnaire containing demographic
      data and data pertaining to allergy, traditional medical and surgical treatment
      use of CAM, and modalities used. RESULTS: Ninety patients were included. Nineteen
      of them (21%) reported CAM use. This included herbal medicine, vitamins,
      homeopathy, acupuncture, massage, reflexology, yoga, and chiropractics. There was
      a tendency, although not statistically significant, for patients with allergy and
      a history of sinus surgery to use CAM. CONCLUSIONS: The prevalence of CAM use
      among patients with CRS in Israel is high and may correlate with the presence of
      allergies and a history of sinus surgery.

PMID- 19755096
TI  - Ovine CD16+/CD14- blood lymphocytes present all the major characteristics of
      natural killer cells.
AB  - Natural killer (NK) cells have a key role in the innate immune response against
      pathogens because of their cytotoxic properties and production of interferon
      gamma (IFN-gamma). Some insight into ruminant NK cell biology has been gained
      through the characterization of bovine NK cells as NKp46(+)/CD3(-) cells.
      However, ovine NK cells have been little studied because of the lack of specific
      antibodies. Most NK cells in humans and cattle express CD16. We found that an
      antibody against human CD16 that cross-reacts with bovine NK cells also
      recognizes cell populations in ovine peripheral blood mononuclear cells. Using
      double labelling with CD14 revealed the same profile as described in other
      species, and we identified a putative NK cell population. We therefore sorted
      this ovine CD16(+)/CD14(-) cell population and tested it for NK cell
      characteristics. More than 80% of sorted CD16(+)/CD14(-) cells expressed
      perforin. After a week of culture in the presence of IL-2 and IL-15, ovine
      CD16(+)/CD14(-) cells had become large cells with intra-cytoplasmic granules
      containing perforin, and the vast majority displayed an activated CD2(
      /low)/CD25(+)/CD8(+) phenotype, as observed for bovine NKp46(+)/CD3(-) cells.
      Moreover, these cells expressed transcripts for the NKp46 receptor, and were
      cytotoxic in a CD16-mediated redirected lysis assay against a murine cell line,
      P815, and in a direct lysis assay against the ovine cell line, IDO5. Finally,
      ovine CD16(+)/CD14(-) cells having expanded for 7 days in culture secreted IFN
      gamma in response to IL-12 in a dosedependent manner. Taken together, these
      findings led us to conclude that the ovine CD16(+)/CD14(-) lymphocyte sub
      population displays the phenotype and functional characteristics of NK cells.

PMID- 19755097
TI  - Live or let die: CCM2 provides the link.
AB  - TrkA receptors are well known for promoting neuronal cell survival. However, in
      some neuroblastic tumors, TrkA activation can instead induce apoptosis. In this
      issue of Neuron, Harel et al. identify CCM2 as a mediator of TrkA-dependent cell
      death, suggesting that CCM2 is a distinctive type of tumor suppressor that
      modulates tyrosine kinase signaling.

PMID- 19755098
TI  - It's in my eyes, but it doesn't look that way to me.
AB  - In this issue of Neuron, Hannula and Ranganath provide striking evidence that
      hippocampal activity predicts eye movements that reveal memory for the past even
      when participants' overt memory decisions are in error. Their findings bear on an
      ongoing debate about the relationship between mnemonic awareness and hippocampal
      function.

PMID- 19755099
TI  - Nicotine's Allure.
AB  - Both conscious and unconscious memory mechanisms contribute to the rewarding
      effects of nicotine and other drugs of abuse. In this issue of Neuron, Tang and
      Dani use in vivo measures of synaptic plasticity in freely moving mice to link
      nicotine-induced dopamine release in hippocampus to LTP induction and behavioral
      reinforcement.

PMID- 19755100
TI  - A new ion channel blooms at the synapse.
AB  - A new study by Yao et al. in the current issue of Cell proposes that a novel
      vesicular protein, dubbed Flower, regulates endocytosis by controlling
      presynaptic Ca(2+) levels. This finding is intriguing not only for its
      implications for vesicle cycling, but also for the multitude of Ca(2+)-dependent
      processes at play in presynaptic nerve terminals.

PMID- 19755101
TI  - Intention, action planning, and decision making in parietal-frontal circuits.
AB  - The posterior parietal cortex and frontal cortical areas to which it connects are
      responsible for sensorimotor transformations. This review covers new research on
      four components of this transformation process: planning, decision making,
      forward state estimation, and relative-coordinate representations. These
      sensorimotor functions can be harnessed for neural prosthetic operations by
      decoding intended goals (planning) and trajectories (forward state estimation) of
      movements as well as higher cortical functions related to decision making and
      potentially the coordination of multiple body parts (relative-coordinate
      representations).

PMID- 19755102
TI  - CCM2 mediates death signaling by the TrkA receptor tyrosine kinase.
AB  - The TrkA receptor tyrosine kinase is crucial for differentiation and survival of
      nerve-growth-factor-dependent neurons. Paradoxically, TrkA also induces cell
      death in pediatric tumor cells of neural origin, via an unknown mechanism. Here,
      we show that CCM2, a gene product associated with cerebral cavernous
      malformations, interacts with the juxtamembrane region of TrkA via its
      phosphotyrosine binding (PTB) domain and mediates TrkA-induced death in diverse
      cell types. Both the PTB and Karet domains of CCM2 are required for TrkA
      dependent cell death, such that the PTB domain determines the specificity of the
      interaction, and the Karet domain links to death pathways. Downregulation of CCM2
      in medulloblastoma or neuroblastoma cells attenuates TrkA-dependent death.
      Combined high expression levels of CCM2 and TrkA are correlated with long-term
      survival in a large cohort of human neuroblastoma patients. Thus, CCM2 is a key
      mediator of TrkA-dependent cell death in pediatric neuroblastic tumors.

PMID- 19755103
TI  - The eyes have it: hippocampal activity predicts expression of memory in eye
      movements.
AB  - Although there is widespread agreement that the hippocampus is critical for
      explicit episodic memory retrieval, it is controversial whether this region can
      also support indirect expressions of relational memory when explicit retrieval
      fails. Here, using functional magnetic resonance imaging (fMRI) with concurrent
      indirect, eye-movement-based memory measures, we obtained evidence that
      hippocampal activity predicted expressions of relational memory in subsequent
      patterns of viewing, even when explicit, conscious retrieval failed.
      Additionally, activity in the lateral prefrontal cortex and functional
      connectivity between the hippocampus and prefrontal cortex were greater for
      correct than for incorrect trials. Together, these results suggest that
      hippocampal activity can support the expression of relational memory even when
      explicit retrieval fails and that recruitment of a broader cortical network may
      be required to support explicit associative recognition.

PMID- 19755104
TI  - Polycomb limits the neurogenic competence of neural precursor cells to promote
      astrogenic fate transition.
AB  - During neocortical development, neural precursor cells (NPCs, or neural stem
      cells) produce neurons first and astrocytes later. Although the timing of the
      fate switch from neurogenic to astrogenic is critical for determining the number
      of neurons, the mechanisms are not fully understood. Here, we show that the
      polycomb group complex (PcG) restricts neurogenic competence of NPCs and promotes
      the transition of NPC fate from neurogenic to astrogenic. Inactivation of PcG by
      knockout of the Ring1B or Ezh2 gene or Eed knockdown prolonged the neurogenic
      phase of NPCs and delayed the onset of the astrogenic phase. Moreover, PcG was
      found to repress the promoter of the proneural gene neurogenin1 in a
      developmental-stage-dependent manner. These results demonstrate a role of PcG:
      the temporal regulation of NPC fate.

PMID- 19755105
TI  - LIG family receptor tyrosine kinase-associated proteins modulate growth factor
      signals during neural development.
AB  - Genome-wide screens were performed to identify transmembrane proteins that
      mediate axonal growth, guidance and target field innervation of somatosensory
      neurons. One gene, Linx (alias Islr2), encoding a leucine-rich repeat and
      immunoglobulin (LIG) family protein, is expressed in a subset of developing
      sensory and motor neurons. Domain and genomic structures of Linx and other LIG
      family members suggest that they are evolutionarily related to Trk receptor
      tyrosine kinases (RTKs). Several LIGs, including Linx, are expressed in subsets
      of somatosensory and motor neurons, and select members interact with TrkA and Ret
      RTKs. Moreover, axonal projection defects in mice harboring a null mutation in
      Linx resemble those in mice lacking Ngf, TrkA, and Ret. In addition, Linx
      modulates NGF-TrkA- and GDNF-GFRalpha1/Ret-mediated axonal extension in cultured
      sensory and motor neurons, respectively. These findings show that LIGs physically
      interact with RTKs and modulate their activities to control axonal extension,
      guidance and branching.

PMID- 19755106
TI  - Neuroligin 2 drives postsynaptic assembly at perisomatic inhibitory synapses
      through gephyrin and collybistin.
AB  - In the mammalian CNS, each neuron typically receives thousands of synaptic inputs
      from diverse classes of neurons. Synaptic transmission to the postsynaptic neuron
      relies on localized and transmitter-specific differentiation of the plasma
      membrane with postsynaptic receptor, scaffolding, and adhesion proteins
      accumulating in precise apposition to presynaptic sites of transmitter release.
      We identified protein interactions of the synaptic adhesion molecule neuroligin 2
      that drive postsynaptic differentiation at inhibitory synapses. Neuroligin 2
      binds the scaffolding protein gephyrin through a conserved cytoplasmic motif and
      functions as a specific activator of collybistin, thus guiding membrane tethering
      of the inhibitory postsynaptic scaffold. Complexes of neuroligin 2, gephyrin and
      collybistin are sufficient for cell-autonomous clustering of inhibitory
      neurotransmitter receptors. Deletion of neuroligin 2 in mice perturbs GABAergic
      and glycinergic synaptic transmission and leads to a loss of postsynaptic
      specializations specifically at perisomatic inhibitory synapses.

PMID- 19755107
TI  - NCS-1 in the dentate gyrus promotes exploration, synaptic plasticity, and rapid
      acquisition of spatial memory.
AB  - The molecular underpinnings of exploration and its link to learning and memory
      remain poorly understood. Here we show that inducible, modest overexpression of
      neuronal calcium sensor 1 (Ncs1) selectively in the adult murine dentate gyrus
      (DG) promotes a specific form of exploratory behavior. The mice also display a
      selective facilitation of long-term potentiation (LTP) in the medial perforant
      path and a selective enhancement in rapid-acquisition spatial memory, phenotypes
      that are reversed by direct application of a cell-permeant peptide (DNIP)
      designed to interfere with NCS-1 binding to the dopamine type-2 receptor (D2R).
      Moreover, the DNIP and the D2R-selective antagonist L-741,626 attenuated
      exploratory behavior, DG LTP, and spatial memory in control mice. These data
      demonstrate a role for NCS-1 and D2R in DG plasticity and provide insight for
      understanding how the DG contributes to the origin of exploration and spatial
      memory acquisition.

PMID- 19755108
TI  - Differences in cortical versus subcortical GABAergic signaling: a candidate
      mechanism of electroclinical uncoupling of neonatal seizures.
AB  - Electroclinical uncoupling of neonatal seizures refers to electrographic seizure
      activity that is not clinically manifest. Uncoupling increases after treatment
      with Phenobarbital, which enhances the GABA(A) receptor (GABA(A)R) conductance.
      The effects of GABA(A)R activation depend on the intracellular Cl(-)
      concentration ([Cl(-)](i)) that is determined by the inward Cl(-) transporter
      NKCC1 and the outward Cl(-) transporter KCC2. Differential maturation of Cl(-)
      transport observed in cortical versus subcortical regions should alter the
      efficacy of GABA-mediated inhibition. In perinatal rat pups, most thalamic
      neurons maintained low [Cl(-)](i) and were inhibited by GABA. Phenobarbital
      suppressed thalamic seizure activity. Most neocortical neurons maintained higher
      [Cl(-)](i), and were excited by GABA(A)R activation. Phenobarbital had
      insignificant anticonvulsant responses in the neocortex until NKCC1 was blocked.
      Regional differences in the ontogeny of Cl(-) transport may thus explain why
      seizure activity in the cortex is not suppressed by anticonvulsants that block
      the transmission of seizure activity through subcortical networks.

PMID- 19755109
TI  - Dopamine enables in vivo synaptic plasticity associated with the addictive drug
      nicotine.
AB  - Addictive drugs induce a dopamine signal that contributes to the initiation of
      addiction, and the dopamine signal influences drug-associated memories that
      perpetuate drug use. The addiction process shares many commonalities with the
      synaptic plasticity mechanisms normally attributed to learning and memory.
      Environmental stimuli repeatedly linked to addictive drugs become learned
      associations, and those stimuli come to elicit memories or sensations that
      motivate continued drug use. Applying in vivo recording techniques to freely
      moving mice, we show that physiologically relevant concentrations of the
      addictive drug nicotine directly cause in vivo hippocampal synaptic potentiation
      of the kind that underlies learning and memory. The drug-induced long-term
      synaptic plasticity required a local hippocampal dopamine signal. Disrupting
      general dopamine signaling prevented the nicotine-induced synaptic plasticity and
      conditioned place preference. These results suggest that dopaminergic signaling
      serves as a functional label of salient events by enabling and scaling synaptic
      plasticity that underlies drug-induced associative memory.

PMID- 19755110
TI  - Temporal framing of thalamic relay-mode firing by phasic inhibition during the
      alpha rhythm.
AB  - Several aspects of perception, particularly those pertaining to vision, are
      closely linked to the occipital alpha (alpha) rhythm. However, how the alpha
      rhythm relates to the activity of neurons that convey primary visual information
      is unknown. Here we show that in behaving cats, thalamocortical neurons in the
      lateral geniculate nucleus (LGN) that operate in a conventional relay-mode form
      two groups where the cumulative firing is subject to a cyclic suppression that is
      centered on the negative alpha rhythm peak in one group and on the positive peak
      in the other. This leads to an effective temporal framing of relay-mode output
      and results from phasic inhibition from LGN interneurons, which in turn are
      rhythmically excited by thalamocortical neurons that exhibit high-threshold
      bursts. These results provide a potential cellular substrate for linking the
      alpha rhythm to perception and further underscore the central role of inhibition
      in controlling spike timing during cognitively relevant brain oscillations.

PMID- 19755111
TI  - Recollection, familiarity, and cortical reinstatement: a multivoxel pattern
      analysis.
AB  - Episodic memory retrieval is thought to involve reinstatement of the
      neurocognitive processes engaged when an episode was encoded. Prior fMRI studies
      and computational models have suggested that reinstatement is limited to
      instances in which specific episodic details are recollected. We used multivoxel
      pattern-classification analyses of fMRI data to investigate how reinstatement is
      associated with different memory judgments, particularly those accompanied by
      recollection versus a feeling of familiarity (when recollection is absent).
      Classifiers were trained to distinguish between brain activity patterns
      associated with different encoding tasks and were subsequently applied to
      recognition-related fMRI data to determine the degree to which patterns were
      reinstated. Reinstatement was evident during both recollection- and familiarity
      based judgments, providing clear evidence that reinstatement is not sufficient
      for eliciting a recollective experience. The findings are interpreted as support
      for a continuous, recollection-related neural signal that has been central to
      recent debate over the nature of recognition memory processes.

PMID- 19755112
TI  - In vitro metal uptake by recombinant human manganese superoxide dismutase.
AB  - Metal uptake by the antioxidant defense metalloenzyme manganese superoxide
      dismutase (MnSOD) is an essential step in the functional maturation of the
      protein that is just beginning to be investigated in detail. We have extended
      earlier in vitro studies on metal binding by the dimeric Escherichia coli apo
      MnSOD to investigate the mechanism of metal uptake by tetrameric human and
      Thermus thermophilus apo-MnSODs. Like the E. coli apo-MnSOD, these proteins also
      bind metal ions in vitro in a thermally activated, pH-sensitive process. However,
      metal uptake by the tetrameric apo-MnSODs exhibits a number of important
      differences. In particular, there is no indication of conformational gating
      requirement for metal binding for these proteins, and the reaction is first-order
      in metal ion. The high concentration of metal ion that is required to achieve
      physiologically relevant metallation rates for tetrameric human apo-MnSOD in
      vitro suggests the possibility that co-translational metal binding or chaperone
      interactions may be required in vivo.

PMID- 19755113
TI  - Inhibition of highly pathogenic avian influenza virus H5N1 replication by the
      small interfering RNA targeting polymerase A gene.
AB  - RNA interference is a form of post-transcriptional gene silencing mediated by
      small interfering RNAs (siRNAs), and it provides a powerful new means to
      specifically inhibit viral infection. In this study, three siRNAs (ps-PA496, ps
      PA1116, and ps-PA1473) targeting the polymerase A (PA) gene of highly pathogenic
      avian influenza virus (HPAIV) H5N1 were designed and evaluated for their
      abilities to inhibit HPAIV replication. Results in vitro showed that the viral
      replication in the siRNAs-treated cells was 78-fold lower than that of the
      control for ps-PA496. Real-time PCR and indirect immunofluorescence assay also
      showed a significant reduction of the viral RNA level and protein expression. In
      vivo results showed a significant decrease of lung virus titers and an increase
      in the survival rate of infected mice pretreated with ps-PA496. These findings
      suggested that siRNAs targeting PA could efficiently inhibit HPAIV replication
      and these conserved regions might become potential therapeutic targets against
      influenza virus infection.

PMID- 19755114
TI  - Meta prediction of protein crystallization propensity.
AB  - Production of high-quality crystals is one of the main bottlenecks in the X-ray
      crystallography driven protein structure determination. Availability of structure
      determination data repositories, such as TargetDB and PepcDB, and flexibility in
      target selection in structural genomics motivate development of methods that
      predict crystallization propensity from a given protein sequence. We introduce a
      novel linear model tree-based meta-predictor, MetaPPCP, which takes advantage of
      the complementarity of state-of-the-art protein crystallization propensity
      predictors to provide predictions with about 80% accuracy. Our method combines
      predictions of XtalPred and CRYSTALP2 with information concerning isoelectric
      point, hydropathy and number of solved structures for similar sequences.
      Empirical comparison shows that MetaPPCP outperforms current predictors including
      OB-Score, XtalPred, ParCrys, and CRYSTALP2. MetaPPCP obtains over 92% accuracy
      for over a half of its predictions that have probability (propensity to be
      predicted as crystallizable or crystallization resistant) of above 0.8. The
      proposed method could provide useful input for target selection procedures of
      current structural genomics efforts.

PMID- 19755115
TI  - Property of cold inducible DEAD-box RNA helicase in hyperthermophilic archaea.
AB  - TK0306 (Tk-DeaD) of hyperthermophilic archaeon Thermococcus kodakaraensis is
      annotated as the DEAD-box helicase gene; nevertheless, its ortholog has not been
      identified in closely related genera, Pyrococcus spp., which generally grow at
      higher temperature than T. kodakaraensis, suggesting that the cold-inducible RNA
      helicase of Tk-DeaD functions under cold stress conditions. Quantitative RT-PCR
      revealed that Tk-deaD was more dominantly transcribed at 60 degrees C than at 85
      degrees C and 93 degrees C in both logarithmic and stationary phases. Immunoblot
      analyses revealed that Tk-DeaD was detected only in logarithmic-phase cells
      cultivated at 60 degrees C but hardly detected at 85 degrees C and 93 degrees C
      in both phases. Tk-DeaD expression is, hence, post-transcriptionally regulated
      and appears under vigorous growth conditions at 60 degrees C. Recombinant Tk-DeaD
      purified to homogeneity started to unfold at 20 degrees C, fully unfolded at 70
      degrees C, and exhibited maximal ATPase activity and unwinding activity specific
      for single-strand paired RNA at 50 degrees C, which is lower than the growth
      limit of T. kodakaraensis.

PMID- 19755116
TI  - Fluorescence probing of T box antiterminator RNA: insights into riboswitch
      discernment of the tRNA discriminator base.
AB  - The T box transcription antitermination riboswitch is one of the main regulatory
      mechanisms utilized by Gram-positive bacteria to regulate genes that are involved
      in amino acid metabolism. The details of the antitermination event, including the
      role that Mg(2+) plays, in this riboswitch have not been completely elucidated.
      In these studies, details of the antitermination event were investigated
      utilizing 2-aminopurine to monitor structural changes of a model antiterminator
      RNA when it was bound to model tRNA. Based on the results of these fluorescence
      studies, the model tRNA binds the model antiterminator RNA via an induced-fit.
      This binding is enhanced by the presence of Mg(2+), facilitating the complete
      base pairing of the model tRNA acceptor end with the complementary bases in the
      model antiterminator bulge.

PMID- 19755117
TI  - Characterization of the Atg17-Atg29-Atg31 complex specifically required for
      starvation-induced autophagy in Saccharomyces cerevisiae.
AB  - Nutrient starvation induces autophagy to degrade cytoplasmic materials in the
      vacuole/lysosomes. In the yeast, Saccharomyces cerevisiae, Atg17, Atg29, and
      Atg31/Cis1 are specifically required for autophagosome formation by acting as a
      scaffold complex essential for pre-autophagosomal structure (PAS) organization.
      Here, we show that these proteins constitutively form an Atg17-Atg29-Atg31
      ternary complex, in which phosphorylated Atg31 is included. Reconstitution
      analysis of the ternary complex in E. coli indicates that the three proteins are
      included in equimolar amounts in the complex. The molecular mass of a monomeric
      Atg17-Atg29-Atg31 complex is calculated at 97kDa; however, analytical
      ultracentrifugation shows that the molecular mass of the ternary complex is
      198kDa, suggesting a dimeric complex. We propose that this ternary complex acts
      as a functional unit for autophagosome formation.

PMID- 19755118
TI  - Increased serum xylosyltransferase activity in patients with liver fibrosis.
AB  - BACKGROUND: We investigated the xylosyltransferase (XT) activity in the serum of
      liver fibrotic patients with hepatitis C virus induced liver fibrosis at
      different stages as determined according to the scoring system of Desmet and
      Scheuer. METHODS: Measurement of XT activity was performed by liquid
      chromatography-tandem mass spectrometry. RESULTS: We found that serum XT activity
      in males (n=59, median+/-SD, 27.2+/-2.8 mU/L, p<0.001) and females (n=54, 23.6+/
      3.0 mU/L, p<0.01) with liver fibrosis is significantly elevated in comparison to
      a corresponding healthy control cohort of males (n=50, 23.9+/-2.8 mU/L) and
      females (n=52, 21.5+/-3.7 mU/L), respectively. Of note, independent from gender,
      serum XT activity positively correlated with the stage of fibrosis but declined
      again in patients with histologically proven cirrhosis. CONCLUSIONS: XT activity
      is increased in the serum of patients with liver fibrosis at different stages,
      pointing to a possible pathogenetic role in elevated proteoglycan biosynthesis in
      fibrotic remodeling of this organ during chronic injury.

PMID- 19755119
TI  - Murine neonatal infection provides an efficient model for congenital ocular
      toxoplasmosis.
AB  - Congenital infection is one of the most serious settings of infection with the
      apicomplexan parasite Toxoplasma gondii. Ocular diseases, such as
      retinochoroiditis, are the most common sequels of such infection in utero.
      However, while numerous studies have investigated the physiopathology of acquired
      toxoplasmosis, congenital infection has been largely neglected so far. Here, we
      establish a mouse model of congenital ocular toxoplasmosis. Parasite load and
      ocular pathology have been followed for the first 4 weeks of life. Ocular
      infection developed slowly compared to cerebral infection. Even after 4 weeks,
      not all eyes were infected and ocular parasite load was low. Therefore, we
      evaluated a scheme of neonatal infection to overcome problems associated with
      congenital infection. Development of infection and physiopathology was similar,
      but at a higher, more reliable rate. In summary, we have established a valuable
      model of neonatal ocular toxoplasmosis, which facilitates the research of the
      underlying physiopathological mechanisms and new diagnostic approaches of this
      pathology.

PMID- 19755120
TI  - Involvement of SigT and RstA in the differentiation of Streptomyces coelicolor.
AB  - SigT is an ECF sigma factor in Streptomyces coelicolor. sigT and its putative
      anti-sigma factor gene rstA are located in one putative operon, and SigT could
      physically interact with RstA. Deletion of sigT or rstA caused accelerated
      morphological development and enhanced production of antibiotics, concomitant
      with over-expression of chpE, chpH, actII-orf4 and redD. Furthermore, SigT was
      undetectable after loss of rstA. These data suggested that SigT has a negative
      role on differentiation and that RstA negatively regulates the SigT activity
      through a putative antagonistic mechanism and at the post-transcriptional level.

PMID- 19755121
TI  - Activation of adenylate cyclase by forskolin increases the protein stability of
      RCAN1 (DSCR1 or Adapt78).
AB  - Overexpression of Regulator of Calcineurin 1 (RCAN1/DSCR1/Adapt78) is known to
      inhibit the calcineurin-NFAT dependent signaling pathway. In this report, we find
      that activation of adenylate cyclase by forskolin increases the expression of
      RCAN1 through the increase of the protein's half-life. The ability of forskolin
      to increase the accumulation of RCAN1 protein is significantly inhibited with
      protein kinase A inhibitors such as KT5720 and H-89. Furthermore, forskolin
      targets the central and C-terminal region of RCAN1 and enhances the inhibitory
      effect of RCAN1 on the calcineurin-mediated activation of NFAT. Our findings
      provide the first evidence that the accumulation of the RCAN1 protein by cAMP
      acts as an important regulatory mechanism in the control of the calcineurin
      dependent cellular pathway.

PMID- 19755122
TI  - Enzymatic activity of the alternative complex III as a menaquinol:auracyanin
      oxidoreductase in the electron transfer chain of Chloroflexus aurantiacus.
AB  - The surprising lack of the cytochrome bc1 complex in the filamentous anoxygenic
      phototrophic bacterium Chloroflexus aurantiacus suggests that a functional
      replacement exists to link the cyclic electron transfer chain. Earlier work
      identified the alternative complex III (ACIII) as a substitute of cytochrome bc1
      complex. Herein, the enzymatic activity of ACIII is studied. The results strongly
      support the view that the ACIII functions as menaquinol:auracyanin oxidoreductase
      in the C. aurantiacus electron transfer chain. Among all the substrates tested,
      auracyanin is the most efficient electron acceptor of ACIII, suggesting that
      ACIII directly transfers the electron to auracyanin instead of cytochrome c-554.
      The lack of sensitivity to common inhibitors of the cytochrome bc1 complex
      indicates a different catalytic mechanism for the ACIII complex.

PMID- 19755123
TI  - Identification and characterisation of the novel amyloid-beta peptide-induced
      protein p17.
AB  - Amyloid-beta peptide (Abeta) achieves neurodegeneration through unknown
      mechanisms. To elucidate some of these mechanisms, we conducted a cDNA
      subtraction analysis of Abeta-mediated neurotoxicity in neuronal cells and
      observed an up-regulation of the novel gene p17. The p17 protein was also found
      elevated in Alzheimer's disease (AD) mouse model. Here, we characterised p17
      primarily in cell lines with respect to its localisation, function and
      physiological expression. We discovered that p17 acts downstream of protein
      kinase C and inhibits the tyrosine receptor kinase B-brain-derived neurotrophic
      factor (TrkB-BDNF) pathway. It impedes survival factors and enhances amyloid
      precursor protein expression thus suggesting its involvement in the Abeta
      mediated pro-apoptotic pathways in AD.

PMID- 19755124
TI  - Melanocortin 1 receptor mutations impact differentially on signalling to the cAMP
      and the ERK mitogen-activated protein kinase pathways.
AB  - Melanocortin 1 receptor (MC1R), a Gs protein-coupled receptor expressed in
      melanocytes, is a major determinant of skin pigmentation, phototype and cancer
      risk. MC1R activates cAMP and mitogen-activated protein kinase ERK1/ERK2
      signalling. When expressed in rat pheochromocytoma cell line cells, the R151C,
      R160W and D294H MC1R variants associated with melanoma and impaired cAMP
      signalling mediated ERK activation and ERK-dependent, agonist-induced neurite
      outgrowth comparable with wild-type. Dose-response curves for ERK activation and
      cAMP production indicated higher sensitivity of the ERK response. Thus, the
      melanoma-associated MC1R mutations impact differently on cAMP and ERK signalling,
      suggesting that cAMP is not responsible for functional coupling of MC1R to the
      ERK cascade.

PMID- 19755125
TI  - Diphosphonucleotide phosphatase/phosphodiesterase (PPD1) from yellow lupin
      (Lupinus luteus L.) contains an iron-manganese center.
AB  - Yellow lupin diphosphonucleotide phosphatase/phosphodiesterase (PPD1) represents
      a novel group of enzymes. Here we report that it possesses one iron atom and one
      manganese atom (1:1 molar ratio) per subunit. The enzyme exhibits visible
      absorption maximum at approximately 530 nm. Prolonged oxidation of PPD1 leads to
      loss of the charge-transfer band and catalytic activity, whereas after reduction
      PPD1 remains active. Replacement of conserved amino-acid residues coordinating
      metals results in the loss of enzymatic activity. Despite low amino-acid sequence
      homology of PPD1 to well-characterized approximately 55-kDa purple acid
      phosphatases, their overall fold, topology of active center and metal content are
      highly similar.

PMID- 19755126
TI  - The scaling of dose with host body mass and the determinants of success in
      experimental cercarial infections.
AB  - Experimental studies of parasite transmission can help to elucidate life cycles,
      measure the success of infective stages under different conditions, or test the
      efficacy of vaccination or other forms of protection against parasitic infection.
      By combining the results of experiments on a particular parasite taxon, one may
      also answer questions such as how experimental infection doses are chosen, or
      what determines infection success. Here, focusing on trematodes, analyses are
      conducted on data compiled from a total of 145 cercarial infection experiments
      (62 on non-schistosomes, 83 on schistosomes) obtained from 115 studies. All of
      these involved experimental exposure of individual hosts to a single known dose
      of cercariae under controlled laboratory conditions. Across these studies, the
      cercarial dose used showed a strong positive relationship with the body mass of
      the target host, independently of the taxonomic identity of that host or of the
      method of infection used. Although justification for the chosen dose was rarely
      given, the larger the target host, the more cercariae it was exposed to. Across
      all experiments, there was also evidence for a weak but significant dose
      dependent effect on infection success: the higher the dose used in an experiment,
      the smaller the proportion of cercariae recovered from the host. This effect was
      mitigated by either host body mass (for schistosomes) or host taxonomic identity
      (for non-schistosomes), with infection being lower in fish than in other host
      types. Experimental procedures also impacted significantly on infection success,
      namely the infection method used (for schistosomes) and the time between
      infection and recovery of parasites (for non-schistosomes). Overall, this
      analysis of published experimental results provides evidence of both biological
      processes and confounding methodological effects, and it provides strong
      arguments for greater rationale in the design of experimental infection studies.

PMID- 19755128
TI  - Cloning of a novel interleukin (IL)-20-like gene in rainbow trout Oncorhynchus
      mykiss gives an insight into the evolution of the IL-10 family.
AB  - A novel IL-20-like (IL-20L) gene has been analyzed in rainbow trout. It has a six
      exon/five intron gene organisation and is translated into 181 amino acids (aa)
      with a signal peptide of 25aa and a mature peptide of 156aa. The trout IL-20L
      translation shares highest identities to other IL-20L molecules from fish and to
      IL-20 in mammals. Phylogenetic analysis showed that the fish IL-20L molecules
      form an independent clade but cluster with the group containing the IL-19, IL-20
      and IL-24 molecules from higher vertebrates with a high bootstrap value (89%).
      The fish IL-20L genes are syntenically in the same location as mammalian IL-19/IL
      20/IL-24. Gene organisation and multiple alignment also showed a close
      relationship of fish IL-20L genes to the mammalian IL-19/IL-20/IL-24 subfamily.
      These data suggest that the fish IL-20L molecules may have arisen from an
      ancestral gene that gave rise to IL-19, IL-20 and IL-24 in higher vertebrates. A
      high level of IL-20L expression in immune related tissues and in the brain,
      suggests an important role of the fish IL-20L molecule in both the fish immune
      system and nervous system. Although the exact cell types expressing IL-20L have
      yet to be defined, macrophages express IL-20L. Moreover, the IL-20L expression in
      the macrophage cell line RTS-11 was modulated by pro-inflammatory cytokines,
      signalling pathway activators, microbial mimics and the immuno-suppressor
      dexamethasone. These data suggest that trout IL-20L is an important player in the
      cytokine network. The increased expression of IL-20L was only detected at late
      stages (4-24h) of LPS stimulation in RTS-11 cells and in spleen 24-72h after
      infection with Yersinia ruckeri, and suggests that the increased expression of IL
      20L by LPS and infection may be via the rapid increase of pro-inflammatory
      cytokines (e.g., IL-1beta) and other factors that is known to occur.

PMID- 19755127
TI  - SDF-1alpha/CXCL12 enhances GABA and glutamate synaptic activity at serotonin
      neurons in the rat dorsal raphe nucleus.
AB  - The serotonin (5-hydroxytryptamine; 5-HT) system has a well-characterized role in
      depression. Recent reports describe comorbidities of mood-immune disorders,
      suggesting an immunological component may contribute to the pathogenesis of
      depression as well. Chemokines, immune proteins which mediate leukocyte
      trafficking, and their receptors are widely distributed in the brain, mediate
      neuronal patterning, and modulate various neuropathologies. The purpose of this
      study was to investigate the neuroanatomical relationship and functional impact
      of the chemokine stromal cell-derived factor-1alpha/CXCL12 and its receptor,
      CXCR4, on the serotonin dorsal raphe nucleus (DRN) system in the rat using
      anatomical and electrophysiological techniques. Immunohistochemical analysis
      indicates that over 70% of 5-HT neurons colocalize with CXCL12 and CXCR4. At a
      subcellular level, CXCL12 localizes throughout the cytoplasm whereas CXCR4
      concentrates to the outer membrane and processes of 5-HT neurons. CXCL12 and
      CXCR4 also colocalize on individual DRN cells. Furthermore, electrophysiological
      studies demonstrate CXCL12 depolarization of 5-HT neurons indirectly via
      glutamate synaptic inputs. CXCL12 also enhances the frequency of spontaneous
      inhibitory and excitatory postsynaptic currents (sIPSC and sEPSC). CXCL12
      concentration-dependently increases evoked IPSC amplitude and decreases evoked
      IPSC paired-pulse ratio selectively in 5-HT neurons, effects blocked by the CXCR4
      antagonist AMD3100. These data indicate presynaptic enhancement of GABA and
      glutamate release at 5-HT DRN neurons by CXCL12. Immunohistochemical analysis
      further shows CXCR4 localization to DRN GABA neurons, providing an anatomical
      basis for CXCL12 effects on GABA release. Thus, CXCL12 indirectly modulates 5-HT
      neurotransmission via GABA and glutamate synaptic afferents. Future therapies
      targeting CXCL12 and other chemokines may treat serotonin related mood disorders,
      particularly depression experienced by immune-compromised individuals.

PMID- 19755129
TI  - A flexible system for hands-free intracranial microinjection.
AB  - Neuroscience research projects often use intracranial (IC) microinfusions to
      target drug delivery to specific brain areas during behavioral testing. These
      experiments require accurate and precisely-timed delivery of small volumes. We
      present here a stepper motor-powered micropump assembly for such delivery. This
      system is hands-free, does not use a potentially leaky fluid swivel or use long
      delivery tubes that are subject to peristaltic forces during animal movements,
      and has been applied in combination with other paradigms. This micropump system
      reliably delivers a wide range of fluid volumes (e.g. 50 nL to 1 microL in tissue
      or greater for intraventricular injections) bilaterally from two independent,
      commercially available microsyringes through standard surgically implanted guide
      cannulae. It is easy to build and disassemble for cleaning or changing
      microsyringes. This system can also be used for a variety of purposes, e.g.
      intracranial self-administration, place conditioning, and many more, with the
      advantage that it provides a way to gather important data in the seconds and
      minutes following IC microinfusion without disruption of the animal's behavior by
      handling.

PMID- 19755130
TI  - Duplex Real Time PCR for the detection of hepatitis A virus in shellfish using
      Feline Calicivirus as a process control.
AB  - The consumption of bivalve shellfish is a common cause of foodborne outbreaks of
      viral origin. The evaluation of the sanitary quality of these products, however,
      is still based on bacterial indicators of fecal contamination (Reg. (EC) No.
      2073/2005 and No.1441/2007) even if it is known that they are not reliable
      indicators of viral contamination. In this study a duplex Real Time PCR method
      for quantitative detection of hepatitis A (HAV) in shellfish was developed.
      Feline Calicivirus (FCV) was used as a control for assessing the effectiveness of
      the concentration and extraction process and the ability to eliminate PCR
      inhibitors present in the food matrix. The specific primers and probes for
      detection of HAV and FCV, chosen respectively from the 5'-UTR region and in the
      ORF1 region, were labeled with two different dyes and detected simultaneously.
      The method was applied on spiked and non-spiked shellfish from a local market.
      The amplification of HAV in the presence of FCV showed good linearity
      (R(2)=0.994) and the sensitivity limit of the reaction was at least 5 x
      10(2)TCID(50)g(-1) of an hepatopancreas extract.

PMID- 19755131
TI  - Development of a World Health Organisation International Reference Panel for Anti
      HIV.
AB  - In response to a recommendation made by the "World Health Organisation (WHO)
      Working Group on Reference Preparations for Testing HBsAg, Anti-HCV and Anti-HIV
      Diagnostic Kits", a reference panel for anti-HIV consisting of plasma samples
      representing the major groups and subtypes of HIV has been prepared. The panel
      consists of solvent-detergent treated anti-HIV-positive human plasma samples that
      have been diluted 1 in 40 in anti-HIV-negative human serum and freeze-dried and
      the anti-HIV-positive plasma samples were derived from individuals infected with
      HIV-1 group M subtypes A, B, C and CRF01_AE, HIV-1 group O and HIV-2. Fifteen
      laboratories from around the world took part in a collaborative study to evaluate
      the reference panel for anti-HIV and were requested to test the panel in as wide
      a range of assays as possible. Where appropriate, serial dilutions were performed
      and samples tested around their end-points to facilitate the comparison of
      analytical sensitivity between assays. For qualitative assays such as Western
      blots and rapid assays, the panel was tested undiluted. Results show that the HIV
      negative serum sample was negative in all assays (except for a small number of
      Western blot assays) and that all HIV-positive samples were detected in all
      assays, with the exception of an anti-HIV-2 EIA that did not detect most HIV-1
      samples and a small number of assays that failed to detect the group O sample.
      Considerable variability was seen in the end-point titres obtained with the
      various assays. A report on the study was submitted to the WHO Expert Committee
      on Biological Standardisation (ECBS) and the panel established as the 1st
      International Reference Panel for Anti-HIV (code 02/210); a unitage was not
      assigned to the panel members.

PMID- 19755132
TI  - Detection of red-spotted grouper nervous necrosis virus by loop-mediated
      isothermal amplification.
AB  - Red-spotted grouper nervous necrosis virus (RGNNV) causes high mortality in
      marine fish larvae cultured in China. To control better an outbreak of this
      virus, a rapid, specific and sensitive detection method based on loop-mediated
      isothermal amplification (LAMP) was developed. A set of four primers, two outer
      and two inner, was designed from RGNNV genome RNA. The LAMP reaction mix was
      optimized. The method was specific as no cross-reaction was observed between
      white spot syndrome virus, koi herpesvirus, infectious spleen and kidney necrosis
      virus, mud crab reovirus, and grass carp hemorrhage virus. The sensitivity of
      LAMP was 100-fold higher than the nested PCR in detecting the presence of RGNNV.
      RGNNV was detected in the brain of Trachinotus ovatus that showed typical
      symptoms of NNV infection, with the standardized LAMP procedure.

PMID- 19755133
TI  - Nonexploratory movement and behavioral alterations in a thalidomide or valproic
      acid-induced autism model rat.
AB  - Autism is a behaviorally characterized disorder with impairments in social
      interactions, as well as stereotyped, repetitive patterns of behaviors and
      interests. Exposure of rat fetuses to thalidomide (THAL) or valproic acid (VPA)
      on the ninth day of gestation has been reported as a useful model for human
      autism. We have shown that early serotonergic neural development is disrupted in
      these rats. In the current study, we used a radial maze and open field
      experimental paradigm to investigate whether these rats present behavioral and/or
      learning aberrations. THAL (500mg/kg), VPA (800mg/kg), or vehicle was
      administered orally to E9 pregnant rats at 7-10 weeks of age. Although the mean
      number of correct and incorrect arm choices in the initial eight arm choices did
      not differ between control and teratogen-exposed groups, achievement of learning
      (seven or eight consecutive correct choices for 3 consecutive days for individual
      rats) seemed to be impaired in teratogen-exposed groups. Interestingly, average
      time to explore the maze task was shorter in the teratogen-exposed groups,
      indicating that correct choice might be due to mere coincidence (i.e.,
      nonexploratory movement). Unexpectedly, no significant differences were observed
      in social interaction in these rats. These results indicate that prenatal
      exposure to THAL and VPA might alter behavior in a manner that is, in part,
      consistent with human autism.

PMID- 19755134
TI  - Direct synaptic connections between superior colliculus afferents and thalamo
      insular projection neurons in the feline suprageniculate nucleus: a double
      labeling study with WGA-HRP and kainic acid.
AB  - The suprageniculate nucleus (Sg) of the feline thalamus, which subserves largely
      unimodal sensory and orientation behavior, receives input from the deep layers of
      the superior colliculus (SC), and projects to the suprasylvian cortical areas,
      such as the anterior ectosylvian visual area and the insular visual area (IVA),
      which contain visually responsive neurons. Through a double tract-tracing
      procedure involving the injection of wheat germ agglutinin conjugated with
      horseradish peroxidase (WGA-HRP) into the IVA and the injection of kainic acid
      into the SC, this study sought to determine the nature of the synaptic
      relationship between the SC afferents and the thalamo-cortical projection
      neurons. WGA-HRP injections labeled numerous neurons in the Sg, while kainic acid
      injections destroyed many tectothalamic terminals in the Sg. The distributions of
      the WGA-HRP-labeled neurons and the degenerated axon terminals overlapped in the
      dorsal part of the Sg. Electron microscopic observations demonstrated that the
      degenerated axon terminals made synaptic contacts with the dendrites of the WGA
      HRP-labeled neurons in this overlapping region of the Sg. These results provide
      the first anatomical evidence that the Sg may play a role in the key relay of
      visual information from the SC to the IVA, within an identified extrageniculo
      cortical pathway.

PMID- 19755135
TI  - Sex-specific expression of BDNF and CART in the midbrain non-preganglionic
      Edinger-Westphal nucleus in the rat.
AB  - In mammals, females generally appear more vulnerable to stressors than males. The
      non-preganglionic Edinger-Westphal nucleus (npEW) has been implicated in
      regulation of the stress response. Brain-derived neurotrophic factor (BDNF) and
      cocaine- and amphetamine-related transcript peptide (CART) are sex-specifically
      involved in the stress response too, and are present in the human and rat npEW.
      We hypothesized that male and female rats would differ in the expression of BDNF
      and CART in the npEW. Using immunocytochemistry and in situ hybridization we
      found that BDNF, CART and the estrogen receptor beta (ERbeta) are colocalized in
      the npEW. Q-RT-PCR showed no differences in CART and BDNF coding mRNAs between
      males and females, but quantitative immunocytochemistry revealed a 16% lower
      number of BDNF-immunoreactive neurons, and 19% lower CART-immunoreactivity in
      females compared to males. Considering the fact that Ucn1, CART and BDNF are co
      expressed in the npEW with ERbeta and their protein expression differs between
      males and females, we propose that the functioning of the npEW may contribute to
      the sex differences that exist in stress sensitivity.

PMID- 19755136
TI  - Mitochondrial tRNAs as light strand replication origins: similarity between
      anticodon loops and the loop of the light strand replication origin predicts
      initiation of DNA replication.
AB  - Stem-loop hairpins formed by mitochondrial light strand replication origins (OL)
      and by heavy strand DNA coding for tRNAs that form OL-like structures initiate
      mitochondrial replication. The loops are recognized by one of the two active
      sites of the vertebrate mitochondrial gamma polymerase, which are homologous to
      the active sites of class II amino-acyl tRNA synthetases. Therefore, the
      polymerase site recognizing the OL loop could recognize tRNA anticodon loops and
      sequence similarity between anticodon and OL loops should predict initiation of
      DNA replication at tRNAs. Strengths of genome-wide deamination gradients starting
      at tRNA genes estimate extents by which replication starts at that tRNA.
      Deaminations (A-->G and C-->T) occur proportionally to time spent single stranded
      by heavy strand DNA during mitochondrial light strand replication. Results show
      that deamination gradients starting at tRNAs are proportional to sequence
      similarity between OL and tRNA loops: most for anticodon-, least D-, intermediate
      for TpsiC-loops, paralleling tRNA synthetase recognition interactions with these
      tRNA loops. Structural and sequence similarities with regular OLs predict OL
      function, loop similarity is dominant in most tRNAs. Analyses of sequence
      similarity and structure independently substantiate that DNA sequences coding for
      mitochondrial tRNAs sometimes function as alternative OLs. Pathogenic mutations
      in anticodon loops increase similarity with the human OL loop, non-pathogenic
      polymorphisms do not. Similarity/homology alignment hypotheses are experimentally
      testable in this system.

PMID- 19755137
TI  - DHEA-Bodipy--a functional fluorescent DHEA analog for live cell imaging.
AB  - The androgen dehydroepiandrosterone (DHEA) has been reported to protect neuronal
      cells against dysfunction and apoptosis. Several signaling pathways involved in
      these effects have been described but little is known about the intracellular
      trafficking of DHEA. We describe design, synthesis and characterization of DHEA
      Bodipy, a novel fluorescent DHEA analog. DHEA-Bodipy proved to be a functional
      DHEA derivative: DHEA-Bodipy (i) induced estrogen receptor alpha-mediated gene
      activation, (ii) protected PC12 rat pheochromocytoma cells against serum
      deprivation-induced apoptosis, and (iii) induced stress fibers and focal adhesion
      contacts in SH-SY5Y human neuroblastoma cells. DHEA-Bodipy bound rapidly and
      specifically to plasma membranes of living PC12 cells. We analyzed metabolism and
      trafficking of DHEA-Bodipy in human neuroblastoma cells. DHEA-Bodipy is the first
      functional fluorescent DHEA derivative suitable for live cell imaging of
      intracellular DHEA transport and localization.

PMID- 19755138
TI  - Modulation of ER alpha transcriptional activity by the orphan nuclear receptor
      ERR beta and evidence for differential effects of long- and short-form splice
      variants.
AB  - Oestrogen receptor related proteins (ERRs) affect target gene expression without
      binding oestradiol. We investigated the functional activity of two splice variant
      isoforms of ERR beta (ERR beta S [short], ERR beta L [long]) expressed in human
      endometrium, where they are coexpressed with the oestrogen receptor alpha (ER
      alpha). Over-expression of ERRbetaL enhanced ER alpha-dependent ligand-induced
      activation of an ERE-luciferase reporter construct, altered the induction of c
      myc mRNA and increased proliferation of Ishikawa cells whereas ERR beta S was
      found to reduce these endpoints. Fluorescent recovery after photobleaching (FRAP)
      revealed that intra-nuclear mobility of YFP-ERR beta S was more rapid than YFP
      ERR beta L. Fluorescence resonance energy transfer (FRET) assays revealed a close
      association between ERR beta L and ER alpha following addition of ligand. We
      speculate that ERR beta L may alter ER alpha-dependent gene activation by
      enhancing the recruitment of co-activators. In conclusion, variant isoforms of
      ERR beta have differential effects on ER alpha-dependent gene expression and this
      has implications for human endometrial cell function.

PMID- 19755139
TI  - Cis-acting elements responsible for dopaminergic neuron-specific expression of
      zebrafish slc6a3 (dopamine transporter) in vivo are located remote from the
      transcriptional start site.
AB  - The purpose of this study was to analyze the transcriptional regulation of the
      zebrafish solute carrier family 6 member 3 gene (slc6a3, dopamine transporter,
      dat), as a first step towards isolating regulatory sequences useful for driving
      transgene expression within dopaminergic neurons of the zebrafish CNS in vivo. We
      found that the 3.0 kb slc6a3 mRNA is expressed in each of the major groups of
      dopaminergic neurons previously identified in the zebrafish CNS. The slc6a3 gene
      spans >20 kb of genomic DNA and contains 15 exons. The genomic organization of
      slc6a3 is highly conserved with respect to its human orthologue, including the
      presence of an untranslated first exon. The promoter lacks a canonical TATA box
      and there are multiple transcriptional start sites. Functional analysis of cis
      acting elements responsible for the expression pattern of slc6a3 was carried out
      by generating stable transgenic zebrafish lines expressing fluorescent reporters
      under transcriptional control of fragments of slc6a3 genomic sequence. The region
      between -2 kb and +5 kb with respect to the transcriptional start site contains
      the core slc6a3 promoter, in addition to neuronal enhancers and/or non-neuronal
      repressors that restrict expression to the CNS, but this region lacks cis-acting
      elements responsible for slc6a3 expression in dopaminergic neurons. The upstream
      sequence between -6 kb and -2 kb contains an enhancer element that drives slc6a3
      expression in dopaminergic neurons of the pretectal region, and additional
      sequences that partially repress expression in non-dopaminergic neurons. However,
      expression of slc6a3 in dopaminergic neurons of the ventral diencephalon and
      telencephalon is dependent on elements that lie outside the region -6 kb to +5
      kb. These data provide a detailed analysis of the slc6a3 gene and show that its
      expression in different populations of dopamine neurons is driven by discrete
      enhancers, rather than a single target sequence for a terminal factor involved in
      specifying neurochemical phenotype.

PMID- 19755140
TI  - Anti-inflammatory and analgesic properties of cis-mulberroside A from Ramulus
      mori.
AB  - This study examined the analgesic and anti-inflammatory actions of cis
      mulberroside A isolated from Ramulus mori in several models of inflammatory pain
      in mice. Cis-mulberroside A (25 and 50mg/kg) given by p.o. route 30 min before
      challenge produced a dose-dependent inhibition of the acetic acid-induced pain
      and Evans blue leakage in mice. In addition, this compound exhibited significant
      systemic anti-inflammatory activity in carrageenan-induced mouse paw edema in a
      concentration-related manner (33.1-68.5% inhibition), and similar results were
      achieved in formalin test. Suppressive effects of cis-mulberroside A on the
      production of NO and expression of inducible nitric oxide synthase (iNOS) in
      lipopolysaccharide (LPS)-stimulated macrophages were also assessed. Collectively,
      cis-mulberroside A showed high analgesic and anti-inflammatory activities. The
      above results will be the supporting evidence for the potential anti-rheumatoid
      activity of R.mori in Chinese traditional medicine.

PMID- 19755141
TI  - Antimycobacterial terpenoids from Juniperus communis L. (Cuppressaceae).
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Juniperus communis is a plant which has been
      reported as a traditional cure for tuberculosis (TB) and other respiratory
      diseases. AIM OF THE STUDY: The aim of this study was to isolate and identify the
      constituents responsible for the activity of the n-hexane extract of Juniperus
      communis roots against Mycobacterium tuberculosis H(37)Rv and Juniperus communis
      aerial parts against Mycobacterium aurum. Subsequently, it was to evaluate the
      activity of the pure isolated compounds against (i) drug-resistant Mycobacterium
      tuberculosis variants, (ii) non-replicating Mycobacterium tuberculosis and (iii)
      a range of non-tuberculous mycobacteria (NTM). MATERIALS AND METHODS: The
      antimycobacterial activity of Juniperus communis extracts, fractions and
      constituents was determined against Mycobacterium tuberculosis H(37)Rv, and
      against rifampicin-, isoniazid-, streptomycin- and moxifloxacin-resistant
      variants, using the microplate broth Alamar Blue assay (MABA) method. Isolated
      constituents were tested against non-replicating Mycobacterium tuberculosis
      H(37)Rv, using the low oxygen recovery assay (LORA), and against NTM
      (Mycobacterium aurum, Mycobacterium phlei, Mycobacterium fortuitum and
      Mycobacterium smegmatis), using a broth microdilution method. Cytotoxicity
      studies were performed using mammalian Vero cells. RESULTS: The antimycobacterial
      activity of Juniperus communis was attributed to a sesquiterpene identified as
      longifolene (1) and two diterpenes, characterised as totarol (2) and trans
      communic acid (3). All compounds were identified following analysis of their
      spectroscopic data (1D- and 2D-NMR, MS) and by comparison with the literature and
      commercial authentic standards when available. Revised assignments for 3 are
      reported. Totarol showed the best activity against Mycobacterium tuberculosis
      H(37)Rv (MIC of 73.7 microM). It was also most active against the isoniazid-,
      streptomycin-, and moxifloxacin-resistant variants (MIC of 38.4, 83.4 and 60
      microM, respectively). Longifolene and totarol were most active against the
      rifampicin-resistant variant (MICs of 24 and 20.2 microM, respectively). Totarol
      showed the best activity in the LORA assay (MIC of 81.3 microM) and against all
      NTM species (MICs in the range of 7-14 microM). Trans-communic acid showed good
      activity against Mycobacterium aurum (MIC of 13.2 microM). The low selectivity
      indices (SI) obtained following cytotoxicity studies indicated that the isolated
      terpenoids were relatively toxic towards mammalian cells. This is the first
      report of the isolation of (1) and (2) from Juniperus communis roots, and of (3)
      from the aerial parts. The antimycobacterial activity of (1) and (3), and the
      activity of (2) against Mycobacterium aurum, Mycobacterium fortuitum and
      Mycobacterium phlei, is reported for the first time. The effect of totarol on
      drug-resistant variants and non-replicating Mycobacterium tuberculosis has never
      been published. CONCLUSIONS: The presence of antimycobacterial terpenoids in
      Juniperus communis aerial parts and roots justifies, to some extent, the
      ethnomedicinal use of this species as a traditional anti-TB remedy.

PMID- 19755142
TI  - Prevalence of the set-1B and astA genes encoding enterotoxins in uropathogenic
      Escherichia coli clinical isolates.
AB  - One hundred seventy human uropathogenic Escherichia coli (UPEC) clinical isolates
      were compared with 35 E. coli strains isolated from feces of a control group to
      determine the presence of the set1, sen and astA genes encoding the ShET-1, ShET
      2, and EAST toxins, respectively. Overall, 27 (16%), 8 (8%) and 0 UPEC isolates
      presented the set1B, the astA, and the sen genes, respectively. This is the first
      time the set gene has been found in UPEC clinical isolates.

PMID- 19755143
TI  - Oxidative stress, calcium homeostasis, and altered gene expression in human lung
      epithelial cells exposed to ZnO nanoparticles.
AB  - The influence of 20nm ZnO nanoparticles on cytotoxicity, oxidative stress,
      intracellular calcium homeostasis, and gene expression was studied in human
      bronchial epithelial cells (BEAS-2B). ZnO caused a concentration- and time
      dependent cytotoxicity while elevating oxidative stress and causing membrane
      damage (cellular LDH release). There was a remarkably steep relationship between
      concentration and toxicity at concentrations from 5 to 10microg/ml. Cytotoxicity
      was completely abolished by the antioxidant N-acetylcysteine (NAC). Exposure to
      ZnO also increased intracellular calcium levels ([Ca(2+)](in)) in a concentration
      and time-dependent manner that was partially attenuated by NAC. Nifedipine, a
      calcium channel blocker, partially attenuated the elevated [Ca(2+)](in),
      indicating that some of the excess [Ca(2+)](in) is a result of influx from
      outside the cell. The relationships between oxidative stress, [Ca(2+)](in), and
      cytotoxicity are discussed. Exposure to a sublethal concentration of ZnO
      increased the expression of four genes that are involved in apoptosis and
      oxidative stress responses BNIP, PRDX3, PRNP, and TXRND1, by at least 2.5-fold.
      Thus, ZnO alters transcriptional regulation in BEAS-2B cells.

PMID- 19755144
TI  - Safety and immunogenicity of GMZ2 - a MSP3-GLURP fusion protein malaria vaccine
      candidate.
AB  - Malaria is a major public health problem in Sub-Saharan Africa. In highly endemic
      regions infants, children and pregnant women are mostly affected. An effective
      malaria vaccine would complement existing malaria control strategies because it
      can be integrated in existing immunization programs easily. Here we present the
      results of the first phase Ia clinical trial of GMZ2 adjuvanted in aluminium
      hydroxide. GMZ2 is a malaria vaccine candidate, designed upon the rationale to
      induce immune responses against asexual blood stages of Plasmodium falciparum
      similar to those encountered in semi-immune individuals. Ten, 30 and 100 microg
      of GMZ2 were well tolerated in 30 healthy malaria-naive German volunteers when
      given three times in monthly intervals. Antigen-specific antibodies as well as
      memory B-cells were induced and detectable throughout the one year follow-up of
      the study. We conclude that GMZ2 is a safe and immunogenic malaria vaccine
      candidate suitable for further clinical development.

PMID- 19755146
TI  - Synthetic peptides from conserved regions of the Plasmodium falciparum early
      transcribed membrane and ring exported proteins bind specifically to red blood
      cell proteins.
AB  - Severe malaria pathology is directly associated with cytoadherence of infected
      red blood cells (iRBCs) to healthy RBCs and/or endothelial cells occurring during
      the intraerythrocytic development of Plasmodium falciparum. We synthesized, as 20
      mer long peptides, the members of the ring exported (REX) protein family encoded
      in chromosome 9, as well as the early transcribed membrane proteins (E-TRAMP)
      10.2 and 4, to identify specific RBC binding regions in these proteins. Twelve
      binding peptides were identified (designated as HABPs): three were identified in
      REX1, two in REX2, one in REX3, two in REX4 and four in E-TRAMP 10.2. The
      majority of these HABPs was conserved among different P. falciparum strains,
      according to sequence analysis. No HABPs were found in E-TRAMP 4. Bindings of
      HABPs were saturable and sensitive to the enzymatic treatment of RBCs and HABPs
      had different structural features, according to circular dichroism studies. Our
      results suggest that the REX and E-TRAMP families participate in relevant
      interactions with RBC membrane proteins, which highlight these proteins as
      potential targets for the development of fully effective immunoprophylactic
      methods.

PMID- 19755145
TI  - Characterisation of a live Salmonella vaccine stably expressing the Mycobacterium
      tuberculosis Ag85B-ESAT6 fusion protein.
AB  - A recombinant Salmonella enterica serovar Typhimurium (S. Typhimurium) vaccine
      strain was constructed that stably expressed the Mycobacterium tuberculosis
      fusion antigen Ag85B-ESAT6 from the chromosome. Live oral vaccination of mice
      with the Salmonella/Ag85B-ESAT6 strain generated a potent anti-Ag85B-ESAT6 T(H)1
      response with high antibody titres with a IgG2a-bias and significant IFN-gamma
      production lasting over a 120-day period. When mice primed with the
      Salmonella/Ag85B-ESAT6 vaccine were mucosally boosted with the Ag85B-ESAT6
      antigen and adjuvant the IFN-gamma responses increased markedly. To determine the
      protective efficacy of this vaccine strain, guinea pigs were immunised and
      followed for a 30-week period after aerosol challenge with M. tuberculosis. The
      heterologous prime-boost strategy of live Salmonella vaccine followed by a
      systemic boost of antigen and adjuvant reduced the levels of M. tuberculosis
      bacteria in the lungs and spleen to the same extent as BCG. Additionally, this
      vaccination regimen was observed to be statistically equivalent in terms of
      protection to immunisation with BCG. Thus, live oral priming with the recombinant
      Salmonella/Ag85B-ESAT6 and boosting with Ag85B-ESAT6 plus the adjuvant LTK63
      represents an effective mucosal vaccination regimen.

PMID- 19755147
TI  - Reproductive and developmental toxicity of degradation products of refrigerants
      in experimental animals.
AB  - The present paper summarizes the results of animal studies on the reproductive
      and developmental toxicity of the degradation products of refrigerants, including
      trifluoroacetic acid (TFA), carbon dioxide (CO(2)), carbon monoxide (CO),
      carbonyl fluoride (CF), hydrogen fluoride (HF) and formic acid (FA). Excessive
      CO(2) in the atmosphere is testicular and reproductive toxic, embryolethal,
      developmentally neurotoxic and teratogenic in experimental animals. As for CO,
      maternal exposure causes prenatal and postnatal lethality and growth retardation,
      skeletal variations, cardiomegaly, blood biochemical, immunological and postnatal
      behavioral changes, and neurological impairment in offspring of several species.
      Very early studies of CO in rats and guinea pigs reported fetal malformations in
      exposed dams. The results of toxicological studies on sodium fluoride (NaF) were
      used to obtain insight into the toxicity of CF and HF, because CF is rapidly
      hydrolyzed in contact with water yielding CO(2) and HF, and NaF is similar in
      kinetics and dynamics to HF. Increased fetal skeletal variation, but not
      malformation, was noted after the maternal administration of NaF. Rat multiple
      generation studies revealed that NaF caused retarded ossification and
      degenerative changes in the lung and kidney in offspring. There is a lack of
      information about the toxicity of TFA and FA.

PMID- 19755148
TI  - Trolox ameliorates 3-nitropropionic acid-induced neurotoxicity in rats.
AB  - 3-nitropropionic acid (3-NPA) is a naturally occurring neurotoxin produced by
      legumes of the genus Astragalus and Arthrium fungi. Acute exposure to 3-NPA
      results in striatal astrocytic death and variety of behavior dysfunction in rats.
      Oxidative stress has been reported to play an important role in 3-NPA-induced
      neurotoxicity. Trolox is a potent free radical chain breaking antioxidant which
      has been shown to restore structure and function of the nervous system following
      oxidative stress. This rapid and efficient antioxidant property of trolox was
      attributed to its enhanced water solubility as compared with alpha-tocopherol.
      This investigation was aimed to study the effect of trolox against 3-NPA-induced
      neurotoxicity in female Wistar rats. The animals received trolox (0, 40 mg, 80 mg
      and 160 mg/kg, orally) daily for 7 days. 3-NPA (25mg/kg, i.p.) was administered
      daily 30 min after trolox for the same duration. One additional group of rats
      served as control (vehicle only). On day 8, the animals were observed for
      neurobehavioral performance. Immediately after behavioral studies, the animal's
      brains were dissected out for histological studies. Lesions in the striatal
      dopaminergic neurons were assessed by immunohistochemical method using tyrosine
      hydroxylase immunostaining. Administration of 3-NPA alone caused significant
      depletion of striatal dopamine and glutathione, whereas, the levels of
      thiobarbituric acid reactive substance (TBARS) and nitric oxide (NO) were
      significantly increased suggesting an elevated level of oxidative stress. Trolox
      significantly and dose-dependently protected animals against 3-NPA-induced
      neurobehavioral, neurochemical and structural abnormalities. These results
      clearly suggest that protective effect of trolox against 3-NPA-induced
      neurotoxicity is mediated through its free radical scavenging activity.

PMID- 19755149
TI  - Practical considerations on the design, execution and analysis of developmental
      neurotoxicity studies to be published in Neurotoxicology and Teratology.
AB  - The present article is an attempt to use the "ILSI Research Foundation/Risk
      Science Institute Reports from the Expert Working Group on Neurodevelopmental
      Endpoints" (2008) to help improve the quality of the manuscripts submitted to
      Neurotoxicology and Teratology, as well as the quality of their review. The
      points discussed in the present paper have been encountered during the peer
      review process. A number of recommendations are proposed on the basis of general
      principles (clarity, full disclosure, and evidence-based interpretation) to help
      authors and reviewers. Clarity of language is a prerequisite, but clarity of
      purpose is essential. The methodology and statistical analysis for each dependent
      variable should be unambiguously presented and justified. Full disclosure
      encompasses a range of topics, such as defining the sample size for each
      experiment, clearly distinguishing between hypothesis-testing and hypothesis
      generating (e.g., a priori vs. a posteriori analyses), clearly defining the
      statistical model appropriate to the study design and questions (e.g., repeated
      measure approach), recognizing and addressing the multiplicity problem (e.g.,
      conceptual unit for the error rate), identifying the appropriate unit for
      statistical analysis (e.g., litter), addressing the results of all analyses
      (e.g., "negative" results are important). Data interpretation should be evidence
      based and not exceed the limits of the findings.

PMID- 19755150
TI  - Spatial and temporal activation of the small GTPases RhoA and Rac1 by the netrin
      1 receptor UNC5a during neurite outgrowth.
AB  - Netrin-1 attracts or repels growing axons during development. The UNC5 receptors
      mediate the repulsive response, either alone or in complex with DCC receptors.
      The signaling mechanisms activated by UNC5 are poorly understood. Here, we
      examined the role of Rho GTPases in UNC5a signaling. We found that UNC5a induced
      neurite outgrowth in N1E-115 neuroblastoma cells in a netrin-1- and Rac1
      dependent manner. UNC5a lacking its cytoplasmic tail also mediated this effect.
      In fibroblasts, UNC5a was able to activate RhoA and to a lower extent Rac1 and
      Cdc42 in response to netrin-1. Using Fluorescence Resonance Energy Transfer
      (FRET) intermolecular probes, we visualized the spatial and temporal activation
      of Rac1, Cdc42 and RhoA in live N1E-115 cells expressing UNC5a during neurite
      outgrowth. We found that Rac1 but not Cdc42 was transiently activated at the
      leading edge of the cell during neurite initiation. However, at later times when
      well-developed neurites were formed, active RhoA was found in the cell body and
      at the base of the neuronal leading process in UNC5a-expressing cells. Together,
      these findings demonstrate that the netrin-1 receptor UNC5a is able to induce
      neurite outgrowth and to differentially activate RhoA and Rac1 during neurite
      extension in a spatial and temporal manner.

PMID- 19755151
TI  - Coupling cellular mitogenesis to apoptosis by designed biomolecules.
AB  - Cellular signal transduction pathways transduce input signals to produce
      corresponding output effects, ensuring correct response to extracellular signals.
      Manipulation of components in signaling pathways will alter correlation of input
      signals to output effects. Here we report that by reconstructing the components
      in mitogenic and apoptotic signaling pathways, Ras, Raf, and caspase-3, we
      manipulated the cells to couple mitogenic signal input to apoptotic output. The
      reconstructed biomolecules that couple mitogenesis to apoptosis are designated as
      "mitogenesis coupled-apoptosis molecular device" (MCAMD). As mitogenesis in
      cancer cells is constitutively active, MCAMD may have potential applications for
      cancer gene therapy.

PMID- 19755152
TI  - Mechanical stretch-induced RhoA activation is mediated by the RhoGEF Vav2 in
      mesangial cells.
AB  - Increased intraglomerular pressure is an important hemodynamic determinant of
      glomerulosclerosis, and can be modelled in vitro by exposing mesangial cells (MC)
      to cyclic mechanical stretch. We have previously shown that the GTPase RhoA
      mediates stretch-induced fibronectin production. Here we investigate the role of
      the RhoGEF Vav2 in the activation of RhoA by stretch. Primary rat MC were exposed
      to 1 Hz cyclic stretch, previously shown to induce maximal RhoA activation at 1
      min. Total Vav2 tyrosine phosphorylation and specific phosphorylation on Y172,
      required for activation, were increased by 1 min of stretch. Overexpression of
      dominant-negative Vav2 Y172/159F in COS-1 cells or downregulation of Vav2 by
      siRNA in MC prevented stretch-induced RhoA activation. Vav2 is known to be
      activated in response to growth factors, and we have previously shown the
      epidermal growth factor receptor (EGFR) to be transactivated by stretch in MC.
      Both Vav2 Y172 phosphorylation and RhoA activation were blocked by the EGFR
      inhibitor AG1478 and prevented in MC overexpressing kinase inactive EGFR. Stretch
      led to physical association between the EGFR and Vav2, and this was dependent on
      EGFR activation. EGFR Y992 phosphorylation, required for growth factor-induced
      Vav2 phosphorylation, was also induced by stretch. Activation of both Src and
      PI3K were necessary upstream mediators of stretch-induced Vav2 Y172
      phosphorylation and RhoA activation. In summary, stretch-induced RhoA activation
      is dependent on transactivation of the EGFR and activation of the RhoGEF Vav2.
      Src and PI3K are both required upstream of Vav2 and RhoA activation.

PMID- 19755153
TI  - Phosphotyrosine protein dynamics in cell membrane rafts of sphingosine-1
      phosphate-stimulated human endothelium: role in barrier enhancement.
AB  - Sphingosine-1-phosphate (S1P), a lipid growth factor, is critical to the
      maintenance and enhancement of vascular barrier function via processes highly
      dependent upon cell membrane raft-mediated signaling events. Anti-phosphotyrosine
      2 dimensional gel electrophoresis (2-DE) immunoblots confirmed that disruption of
      membrane raft formation (via methyl-beta-cyclodextrin) inhibits S1P-induced
      protein tyrosine phosphorylation. To explore S1P-induced dynamic changes in
      membrane rafts, we used 2-D techniques to define proteins within detergent
      resistant cell membrane rafts which are differentially expressed in S1P
      challenged (1microM, 5min) human pulmonary artery endothelial cells (EC), with 57
      protein spots exhibiting >3-fold change. S1P induced the recruitment of over 20
      cell membrane raft proteins exhibiting increasing levels of tyrosine
      phosphorylation including known barrier-regulatory proteins such as focal
      adhesion kinase (FAK), cortactin, p85alpha phosphatidylinositol 3-kinase
      (p85alphaPI3K), myosin light chain kinase (nmMLCK), filamin A/C, and the non
      receptor tyrosine kinase, c-Abl. Reduced expression of either FAK, MLCK,
      cortactin, filamin A or filamin C by siRNA transfection significantly attenuated
      S1P-induced EC barrier enhancement. Furthermore, S1P induced cell membrane raft
      components, p-caveolin-1 and glycosphingolipid (GM1), to the plasma membrane and
      enhanced co-localization of membrane rafts with p-caveolin-1 and p-nmMLCK. These
      results suggest that S1P induces both the tyrosine phosphorylation and
      recruitment of key actin cytoskeletal proteins to membrane rafts, resulting in
      enhanced human EC barrier function.

PMID- 19755155
TI  - Utilising atomic force microscopy for the characterisation of nanoscale drug
      delivery systems.
AB  - The introduction of atomic force microscopy (AFM) techniques has revolutionised
      our ability to characterise colloidal objects. AFM allows the visualisation of
      samples with sub-nanometre resolution in three dimensions in atmospheric or
      submerged conditions. Nanomedical research is increasingly focused on the design,
      characterisation and delivery of nano-sized drug carriers such as nanoparticles,
      liposomes and polyplexes, and this review aims to highlight the scope and
      advantages of AFM in this area. A significant amount of work has been carried out
      in drug delivery system (DDS) research in recent years using a large variety of
      techniques. The use of AFM has enabled us to directly observe very small objects
      without the need of a cumbersome and potentially contaminating sample
      preparation. Thus, nanoscale DDS can be investigated in a controlled environment
      without the necessity of staining or drying. Moreover, intermittent contact mode
      AFM allows the investigation of soft samples with minimal sample alteration;
      phase imaging allows accessing information beyond the sample's topography and
      also differentiating between different materials, and force spectroscopy
      experiments help us to understand the intrinsic structure of DDS by recording the
      elastic or adhesion behaviour of particles. Hence, AFM enables us accessing
      information which is hardly available by other experimental techniques. It has
      provided invaluable information about physicochemical properties and helped to
      shed light on the area of nanoscale drug delivery and will, with more and more
      sophisticated equipment becoming available, continue to add to our understanding
      of the behaviour of nanoscale DDS in the future.

PMID- 19755154
TI  - Genes and signals regulating murine trophoblast cell development.
AB  - A fundamental step in embryonic development is cell differentiation whereby
      highly specialised cell types are developed from a single undifferentiated,
      fertilised egg. One of the earliest lineages to form in the mammalian conceptus
      is the trophoblast, which contributes exclusively to the extraembryonic
      structures that form the placenta. Trophoblast giant cells (TGCs) in the rodent
      placenta form the outermost layer of the extraembryonic compartment, establish
      direct contact with maternal cells, and produce a number of pregnancy-specific
      cytokine hormones. Giant cells differentiate from proliferative trophoblasts as
      they exit the cell cycle and enter a genome-amplifying endocycle. Normal
      differentiation of secondary TGCs is a critical step toward the formation of the
      placenta and normal embryonic development. Trophoblast development is also of
      particular interest to the developmental biologist and immunobiologist, as these
      cells constitute the immediate cellular boundary between the embryonic and
      maternal tissues. Abnormalities in the development of secondary TGCs results in
      severe malfunction of the placenta. Herein we review new information that has
      been accumulated recently regarding the molecular and cellular regulation of
      trophoblast and placenta development. In particular, we discuss the molecular
      aspects of murine TGC differentiation. We also focus on the role of growth and
      transcription factors in TGC development.

PMID- 19755156
TI  - Nano-sized water-in-oil-in-water emulsion enhances intestinal absorption of
      calcein, a high solubility and low permeability compound.
AB  - Our goal was to develop safe and stable multilayer emulsions capable of enhancing
      intestinal absorption of biopharmaceutics classification system (BCS) class III
      drugs. First, w/o emulsions were prepared using calcein as a model BCS class III
      compound and condensed ricinoleic acid tetraglycerin ester as a hydrophobic
      emulsifier. Then water-in-oil-in-water (w/o/w) emulsions were prepared with
      shirasu porous glass (SPG) membranes. Particle size analyses and calcein leakage
      from oil droplets in w/o/w emulsions led us to select stearic acid hexaglycerin
      esters (HS-11) and Gelucire 44/14 as hydrophilic emulsifiers. Analyses of the
      absorption-enhancing effects of w/o/w emulsions on intestinal calcein absorption
      in rats showed that calcein bioavailability after intraduodenal (i.d.)
      administration of HS-11 or Gelucire 44/14+polyvinyl alcohol (PVA) w/o/w emulsions
      prepared with 0.1-microm pore-sized SPGs was significantly higher than that of
      the calcein control. However, serum calcein concentration vs. time profiles after
      i.d. administration of w/o/w emulsions prepared with 1.1-microm and 30-microm
      pore-sized SPGs and an emulsion prepared with a calcein-containing outer water
      phase were comparable to control profiles. These results suggested that HS-11 or
      Gelucire 44/14+PVA are safe outer water phase additives and that 0.1-microm pore
      sized SPGs are important for preparing w/o/w emulsions that enhanced intestinal
      calcein absorption.

PMID- 19755157
TI  - Recent advances in confocal microscopy for studying drug delivery to the eye:
      concepts and pharmaceutical applications.
AB  - Since its seminal introduction 50years ago, confocal microscopy has been applied
      in numerous fields in life sciences. This review presents the different key
      elements of confocal microscopes, in particular scanning techniques, light
      sources and especially laser sources are described in this review. Furthermore,
      an overview of the different image processing systems coupled with confocal
      microscopy is provided. The chapter closes with the applications of confocal
      microscopy in drug delivery to the eye.

PMID- 19755158
TI  - Drug delivery to the brain using surfactant-coated poly(lactide-co-glycolide)
      nanoparticles: influence of the formulation parameters.
AB  - Poly(lactide-co-glycolide) (PLGA) nanoparticles coated with poloxamer 188
      (Pluronic((R)) F-68) or polysorbate 80 (Tween((R)) 80) enable an efficient brain
      delivery of the drugs after intravenous injection. This ability was evidenced by
      two different pharmacological test systems employing as model drugs the anti
      tumour antibiotic doxorubicin and the agonist of opioid receptors loperamide,
      which being P-gp substrates can cross the blood-brain barrier (BBB) only in
      pharmacologically insignificant amounts: binding of doxorubicin to the surfactant
      coated PLGA nanoparticles, however, enabled a high anti-tumour effect against an
      intracranial 101/8 glioblastoma in rats, and the penetration of nanoparticle
      bound loperamide into the brain was demonstrated by the induction of central
      analgesic effects in mice. Both pharmacological tests could demonstrate that
      therapeutic amounts of the drugs were delivered to the sites of action in the
      brain and showed the high efficiency of the surfactant-coated PLGA nanoparticles
      for brain delivery. The results of the study also demonstrated that the efficacy
      of brain delivery by nanoparticles not only is influenced by the coating
      surfactants but also by other formulation parameters such as core polymer, drug,
      and stabilizer.

PMID- 19755159
TI  - Rapamycin or tacrolimus alone fails to resist cardiac allograft accelerated
      rejection mediated by alloreactive CD4(+) memory T cells in mice.
AB  - Donor-reactive memory T (Tm) cells undermine transplanted organs more readily
      than naive T cells. Rapamycin (RAPA) and tacrolimus (FK-506) are current mainstay
      immunosuppressants used for preventing acute allograft rejection. Although their
      efficacy in suppressing naive T cell is established, their suppressing effect on
      memory T cells is undefined. This study was conducted to investigate the
      inhibiting capability of RAPA or FK-506 against transferred alloreactive CD4(+)
      Tm cells in a mouse cardiac transplant model. We found that these drugs alone
      prolonged the median survival time (MST) of allograft from 5days to 9days in
      recipient mice with CD4(+) Tm infusion (P<0.01), which however was not
      significantly longer than that (8days) in untreated recipient mice without CD4(+)
      Tm infusion (naive control). Mean histologic rank of rejection activity in
      section of cardiac allograft on day 5 postgrafting was Grade 4 in the Tm control
      recipients versus Grade 3A in both of the immunosuppressant treatment recipients
      with CD4(+) Tm infusion. RAPA or FK-506 alone failed to completely suppress
      proliferation and differentiation of the alloreactive CD4(+) Tm, which was
      confirmed by in vitro mixed lymphocyte reaction (MLR) and by flow cytometry (FCM)
      of the splenocytes for detecting CD44(high)CD62L(-) effector/memory as well as
      CD69(+)/CD25(+) activation phenotype cells from the respective recipients.
      Furthermore, the agent alone didn't completely inhibit the activation of CD4(+)
      Tm, for serum level of IFN-gamma and its gene expression at the cardiac allograft
      from the immunosuppressant-treated recipients were as still high as the untreated
      naive control. Thus, RAPA or FK-506 alone couldn't completely suppress the
      proliferation and activation of the alloantigen-primed CD4(+) Tm cells responding
      to the alloantigen, indicating that alloreactive CD4(+) Tm was insensitive to
      these immunosuppressants. The characteristics of alloreactive CD4(+) Tm to resist
      immunosuppressants and its potency to initiate quick and vigorous rejection
      despite treatment with the immunosuppressant make it to be a critical barrier to
      prolongation of allograft survival and induction of transplant tolerance.

PMID- 19755160
TI  - Mechanisms involved in the relaxant action of testosterone in the renal artery
      from male normoglycemic and diabetic rabbits.
AB  - Kidney disease is a frequent complication in diabetes, and significant
      differences have been reported between male and female patients. Our working
      hypothesis was that diabetes might modify the vascular actions of testosterone in
      isolated rabbit renal arteries and the mechanisms involved in these actions.
      Testosterone (10(-8) to 10(-4)M) induced relaxation of precontracted arteries,
      without significant differences between control and diabetic rabbits. Both in
      control and diabetic rabbits endothelium removal inhibited testosterone relaxant
      action. In arteries with endothelium, incubation with indomethacin (10(-5)M),
      N(G)-nitro-l-arginine (10(-5)M) or tetraethylammonium (10(-5)M) did not modify
      relaxations to testosterone neither in control nor in diabetic rabbits. In
      endothelium-denuded arteries indomethacin enhanced the relaxant action of
      testosterone, both in control and diabetic rabbits. In arteries from diabetic
      rabbits, eNOS, iNOS and COX-1 expression and testosterone-induced release of
      thromboxane A(2) and prostacyclin were not significantly different from those
      observed in control rabbits. However, COX-2 expression was significantly lower in
      diabetic rabbits that in control rabbits. In nominally Ca(2+)-free medium,
      cumulative addition of CaCl2 (10(-5) to 3x10(-2)M) contracted previously
      depolarized arteries. Testosterone (10(-4)M) inhibited CaCl2 contractions of the
      renal artery both in control and diabetic rabbits. These results show that
      testosterone relaxes the renal artery both in control and diabetic rabbits. This
      relaxation is modulated by muscular thromboxane A(2), it is partially mediated by
      endothelial prostacyclin, and it involves the blocking of extracellular Ca2+
      entry. Diabetes does not modify the mechanisms involved in the relaxant action of
      testosterone in the rabbit renal artery.

PMID- 19755161
TI  - Engineering, expression, and immuno-characterization of recombinant protein
      comprising multi-neutralization sites of rabies virus glycoprotein.
AB  - The rabies virus (RV) glycoprotein (G protein) induces neutralizing antibodies,
      which are important in protection against rabies. In the present study, three
      gene fragments that encode polypeptides (corresponding to amino acid residues 19
      60, 181-219, and 300-458) comprising the linear neutralization sites of the G
      protein were spliced together in tandem by PCR-based site-directed mutagenesis
      and heterologously expressed in Escherichia coli (DE3). The recombinant protein
      (designated rRVg) was purified under denaturing conditions and solubilized by
      stepwise dialysis against an alkaline buffer (0.05 M Na(2)CO(3) pH 9.6). Western
      blot analysis of the antigenicity of rRVg showed that it was recognized by rabies
      immune serum. Competitive neutralization assay revealed that rRVg significantly
      reduced the RV-neutralizing activity of the rabies-immune serum. These results
      show potential of rRVg as a diagnostic antigen for detecting RV-neutralizing
      antibodies in immunized hosts.

PMID- 19755162
TI  - Development of an efficiently cleaved, bioactive, highly pure FLAG-tagged
      recombinant human Mullerian Inhibiting Substance.
AB  - Mullerian Inhibiting Substance (MIS), a member of the TGF-beta family, causes
      regression of the Mullerian duct in male embryos, after binding to Mullerian
      Inhibiting Substance Receptor II (MISRII). It has also been extensively
      demonstrated that it can inhibit proliferation of various cancer cell lines such
      as ovarian, prostate, and breast cancer in vitro and in vivo. Hence, the
      availability of a recombinant, epitope tagged, bioactive MIS is important for the
      selection of patients for treatment and for probing novel molecular targets for
      MIS in various tissues. To this end, we have expressed a recombinant, internally
      FLAG-tagged form of hMIS with the tag (DYKDDDDK) immediately after the cleavage
      site (427-428) of MIS at the C-terminus with a modified dibasic cleavage motif
      sequence. We show that this construct results in a highly pure, endogenously
      processed (cleaved) FLAG MIS, that causes complete regression of the Mullerian
      Duct in an organ culture assay. In addition, purified FLAG MIS was able to bind
      and affinity purify both transfected and endogenous MIS type II receptor. The
      availability of this fully functional, epitope tagged form of MIS should
      facilitate scale-up for preclinical and clinical use and should also be used for
      the study of MIS binding proteins and for tracking in pharmacokinetic studies.

PMID- 19755163
TI  - Inclusion of nuclear intron sequence data helps to identify the Asian sister
      group of New World pitvipers.
AB  - Despite much effort towards resolving the molecular phylogenetic tree for
      pitvipers, some aspects remain unresolved. In particular, the sister group of the
      diverse New World radiation has remained impossible to identify with any
      certainty. In this study, which for the first time includes nuclear intron data
      from all major groups of Asian pitvipers as well as representatives of the New
      World radiation, Bayesian inference allows Gloydius to be identified as the most
      likely sister group to the New World radiation and sheds light on other ambiguous
      relationships among the Old World pitvipers. The sister group relationship of
      "Ovophis"okinavensis and "Trimeresurus"gracilis is confirmed by the addition of
      nuclear genes, and we hypothesise that they form a sister group to the
      Gloydius+New World clade, best supported when the phylogenetic signal from gaps
      is included in the form of a simple-coded matrix.

PMID- 19755164
TI  - Speciation and phylogeography of giant petrels Macronectes.
AB  - We examine global phylogeography of the two forms of giant petrel Macronectes
      spp. Although previously considered to be a single taxon, and despite debate over
      the status of some populations and the existence of minimal genetic data (one
      mitochondrial cytochrome b sequence per form), the current consensus based on
      morphology is that there are two species, Northern Giant Petrel M. halli and
      Southern Giant Petrel M. giganteus. This study examined genetic variation at
      cytochrome b as well as six microsatellite loci in giant petrels from 22 islands,
      representing most island groups at which the two species breed. Both markers
      support separate species status, although sequence divergence in cytochrome b was
      only 0.42% (corrected). Divergence was estimated to have occurred approximately
      0.2mya, but with some colonies apparently separated for longer (up to 0.5 my).
      Three clades were found within giant petrels, which separated approximately
      0.7mya, with the Southern Giant Petrel paraphyletic to a monophyletic Northern
      Giant Petrel. There was evidence of past fragmentation during the Pleistocene,
      with subsequent secondary contact within Southern Giant Petrels. The analysis
      also suggested a period of past population expansion that corresponded roughly to
      the timing of speciation and the separation of an ancestral giant petrel
      population from the fulmar Fulmarus clade.

PMID- 19755165
TI  - Phylogeography's past, present, and future: 10 years after Avise, 2000.
AB  - Approximately 20 years ago, Avise and colleagues proposed the integration of
      phylogenetics and population genetics for investigating the connection between
      micro- and macroevolutionary phenomena. The new field was termed phylogeography.
      Since the naming of the field, the statistical rigor of phylogeography has
      increased, in large part due to concurrent advances in coalescent theory which
      enabled model-based parameter estimation and hypothesis testing. The next phase
      will involve phylogeography increasingly becoming the integrative and comparative
      multi-taxon endeavor that it was originally conceived to be. This exciting
      convergence will likely involve combining spatially-explicit multiple taxon
      coalescent models, genomic studies of natural selection, ecological niche
      modeling, studies of ecological speciation, community assembly and functional
      trait evolution. This ambitious synthesis will allow us to determine the causal
      links between geography, climate change, ecological interactions and the
      evolution and composition of taxa across whole communities and assemblages.
      Although such integration presents analytical and computational challenges that
      will only be intensified by the growth of genomic data in non-model taxa, the
      rapid development of "likelihood-free" approximate Bayesian methods should permit
      parameter estimation and hypotheses testing using complex evolutionary
      demographic models and genomic phylogeographic data. We first review the
      conceptual beginnings of phylogeography and its accomplishments and then
      illustrate how it evolved into a statistically rigorous enterprise with the
      concurrent rise of coalescent theory. Subsequently, we discuss ways in which
      model-based phylogeography can interface with various subfields to become one of
      the most integrative fields in all of ecology and evolutionary biology.

PMID- 19755166
TI  - Typing and susceptibility of bacterial isolates from the fidaxomicin (OPT-80)
      phase II study for C. difficile infection.
AB  - BACKGROUND: Clostridium difficile infection (CDI) has been increasing in
      incidence and severity in recent years, coincident with the spread of a
      "hypervirulent" strain, REA type BI (ribotype 027, PFGE NAP 1). Exacerbating the
      problem has been the observation that metronidazole may be showing decreased
      effectiveness, particularly in the more severe cases. Fidaxomicin is an 18
      membered macrocycle currently in phase 3 trials for the treatment of C. difficile
      infection (CDI). An open-label, phase II study in CDI patients has been completed
      and the clinical results published. C. difficile organisms were isolated from
      patient stool specimens and typed by restriction endonuclease analysis (REA) in
      order to determine the frequency and susceptibility of the C. difficile isolates
      and their response to treatment. METHODS: Fecal samples were plated on CCFA agar
      for isolation of C. difficile. These isolates were tested for susceptibility to
      fidaxomicin, vancomycin, and metronidazole using CLSI agar dilution methods and
      were typed by REA. RESULTS: C. difficile was isolated from 38 of 49 subjects and
      16 (42%) were the epidemic C. difficile BI group. The BI strain was distributed
      approximately equally in the three dosing groups. Overall antibiotic
      susceptibilities were consistent with the previously reported MIC(90) values for
      the three antibiotics tested, but the MIC(90) of BI strains was two dilutions
      higher than non-BI strains for metronidazole and vancomycin (for both
      antibiotics, MIC(90) was 2 microg/mL vs. 0.5 microg/mL, P<0.01 for metronidazole,
      P=NS for vancomycin). Clinical cure for BI isolates (11/14, 79%) was not
      significantly different from non-BI isolates (21/22, 95%). CONCLUSION: These
      results underscore the high prevalence of the BI epidemic strain and demonstrate
      that mild to moderate CDI infection as well as severe disease can be caused by
      these strains. Fidaxomicin cure rates for subjects with BI and with non-BI
      strains are similar, although the small numbers of subjects preclude a robust
      statistical comparison.

PMID- 19755167
TI  - Clostridium difficile infection: historic review.

PMID- 19755168
TI  - Elucidating the Candida albicans calcineurin signaling cascade controlling stress
      response and virulence.
AB  - The protein phosphatase calcineurin is a key mediator of virulence and antifungal
      susceptibility of multiple fungal pathogens including Candida albicans,
      Cryptococcus neoformans, and Aspergillus fumigatus, and has clinical potential as
      a therapeutic target to increase the efficacy of the current antifungal
      armamentarium. Despite the importance of this signaling pathway, few components
      of the calcineurin-signaling pathway are known in C. albicans. Here we identified
      and analyzed additional components of the C. albicans calcineurin cascade,
      including the RCN1 (regulator of calcineurin1), MID1, and CCH1 genes, which
      mediate calcineurin functions in other species. When heterologously expressed in
      Saccharomyces cerevisiae, C. albicans Rcn1 inhibited calcineurin function.
      Although rcn1/rcn1, mid1/mid1, and cch1/cch1 mutant strains share some phenotypes
      with calcineurin mutants, they do not completely recapitulate the phenotypes of a
      calcineurin mutant strain. These studies extend our understanding of the C.
      albicans calcineurin signaling cascade and its host-niche specific role in
      virulence.

PMID- 19755169
TI  - A comparative study of ryanodine receptor (RyR) gene expression levels in a basal
      ray-finned fish, bichir (Polypterus ornatipinnis) and the derived euteleost
      zebrafish (Danio rerio).
AB  - Ryanodine receptors (RyRs) are large homotetrameric protein complexes that
      mediate the release of intracellular stores of calcium. Mammals possess three
      gene copies, RyR1, RyR2, and RyR3 that are expressed in a variety of tissue
      types. Teleost fish express RyR1a and RyR1b genes that are expressed in slow
      twitch skeletal muscle and fast twitch skeletal muscles respectively. Here we
      report the results of a survey of the genome of bichir (Polypterus ornatipinnis),
      considered the most basal ray-finned fish, for its RyR genes. The bichir genome
      encodes four RyR genes, RyR1a, RyR1b, RyR2, and RyR3 that phylogenetically
      cluster with their vertebrate orthologs. Quantitative real time PCR shows fibre
      type-specific expression of the RyR1a and RyR1b genes. The RyR3 gene, however, is
      down regulated in bichir in contrast to derived teleosts including zebrafish in
      which the RyR1 and RyR3 genes are co-expressed at equivalent levels.

PMID- 19755170
TI  - Effect of monoclonal antibody on expression of lipid metabolism related genes in
      porcine adipocytes.
AB  - In order to study the mechanism of monoclonal antibody (McAb) against a porcine
      40-kDa adipocyte-specific plasma membrane protein in reducing fat deposition,
      porcine primary adipocytes were treated with the McAb during the process of
      adipocyte differentiation; its effect on expression of lipid metabolism related
      genes was investigated. Adipocytes were treated with 1-methyl-3
      isobutylmethylxanthine (IDX) plus 10 microg/mL of the McAb or without McAb. The
      mRNA levels of adipocyte differentiation related genes (PPARgamma and
      C/EBPalpha), lipid metabolism related genes (FAS, HSL, CPT-1B, DGAT and A-FABP)
      and adiponectin gene (AdipoQ) were determined using real-time quantitative PCR.
      The results showed that the differentiated adipocyte number and triglyceride (TG)
      content in adipocytes treated with the McAb were lower than that in cells without
      McAb during the whole process of adipocyte differentiation. The McAb
      significantly reduced mRNA expression of PPARgamma, C/EBPalpha, FAS, DGAT, A-FABP
      and adiponectin genes, but increased mRNA expression of HSL and CPT-1B genes
      during the medium and latter stage of adipocyte differentiation. This suggested
      that the McAb decreased triglycerol accumulation in adipocyte by both inhibiting
      adipocyte differentiation and regulating lipid metabolism, especially at the
      medium and latter stage of porcine adipocyte differentiation.

PMID- 19755171
TI  - Differential expression of genes encoding preprobrevinin-2, prepropalustrin-2,
      and preproranatuerin-2 in developing larvae and adult tissues of the mountain
      brown frog Rana ornativentris.
AB  - Previous studies led to the isolation of antimicrobial peptides (AMPs) of the
      brevinin-2, palustrin-2, and ranatuerin-2 families from skin extracts and/or skin
      secretions of the Japanese mountain brown frog, Rana ornativentris. In the
      present study, we cloned cDNAs encoding the precursors of brevinin-2Oc, palustrin
      2Oa, and ranatuerin-2Ob and -2Oe from skin total RNA preparations from adult R.
      ornativentris and established a semi-quantitative RT-PCR system to measure the
      concentrations of these mRNAs. The levels of preprobrevinin-2 and
      preproranatuerin-2 mRNAs in the skin specimens of developing R. ornativentris
      larva were detectable only at stages later than the onset of metamorphosis and
      reached peaks at the stage of metamorphic climax. In contrast, prepropalustrin-2
      mRNA was detected prior to the onset of metamorphosis and levels peaked at stages
      earlier than those of the other two mRNAs. In adult animals, preprobrevinin-2 and
      preproranatuerin-2 gene transcripts were detected at low levels in the small
      intestine and skeletal muscle but not in the stomach, liver, or kidney, whereas
      prepropalustrin-2 gene transcripts were detected at relatively high
      concentrations in all tissues examined. These results indicate that the
      expression of amphibian AMP genes is correlated with metamorphosis but is
      subjected to differential regulation.

PMID- 19755172
TI  - Activities against hemostatic proteins and adrenal gland ultrastructural changes
      caused by the brown widow spider Latrodectus geometricus (Araneae: Theridiidae)
      venom.
AB  - Brown widow spider (BrWS) (Latrodectus geometricus) venom produces intense
      systemic reactions such as cramps, harsh muscle nociceptive, nauseas, vomiting
      and hypertension. The proposed pathogenic mechanisms resulting in these accidents
      have principally been damages occurring at the nervous system. However, it is
      suspected that there is also damage of the adrenal glands, as a result of the
      experimental animal's clinical manifestations, which developed symptoms
      compatible with acute adrenal insufficiency. We have currently found that the
      adrenal gland is damaged by this venom gland homogenates (VGH) producing severe
      alterations on cortex cells resulting in death by acute adrenal insufficiency. In
      general, the ultrastructural study on the glands of mice under transmission
      electronic microscopy observations showed alterations in the majority of the
      intracellular membranes within 3 to 24h. BrWSVGH also showed specific actions on
      extracellular matrix proteins such as fibronectin, laminin and fibrinogen. In
      addition, zymogram experiments using gelatin as substrates detected gelatinolytic
      activity. The molecular exclusion fractionation of crude BrWSVGH resulted in 15
      fractions, of which F1 and F2 presented alpha/beta-fibrinogenase and
      fibronectinolytic activities. Fractions F6, F14 and F15 showed only alpha
      fibrinogenase activity; in contrast, the gelatinolytic action was only observed
      in fraction F11. Only metalloproteinase inhibitors abolished all these
      proteolytic activities. Our results suggest that adrenal cortex lesions may be
      relevant in the etiopathogenesis of severe brown widow spider envenoming. To our
      knowledge, this is the first report on adrenal gland damages, fibrinogenolytic
      activity and interrelations with cell-matrix adhesion proteins caused by
      L.geometricus VGH. The venom of this spider could be inducing hemostatic system
      damages on envenomed patients.

PMID- 19755173
TI  - Information system design for a hospital emergency department: a usability
      analysis of software prototypes.
AB  - STUDY OBJECTIVE: The purpose of this study is to evaluate the usability of
      emergency department (ED) software prototypes developed for Tablet personal
      computers (Tablet PCs) in order to keep electronic health records (EHRs) of
      patients errorless and accessible through mobile technologies. In order to serve
      this purpose, two alternative prototypes were developed for Tablet PCs: Mobile
      Emergency Department Software (MEDS) and Mobile Emergency Department Software
      Iconic (MEDSI) among which the user might choose the more appropriate one for ED
      operations based on a usability analysis involving the target users. METHODS: The
      study is based on a case study of 32 potential users of our prototypes at the ED
      of Kadikoy-AHG in Istanbul, Turkey. We examined usability of the prototypes for
      medical information systems by means of Nielsen's heuristic evaluation and
      cognitive walkthrough methods relying on 7-point scales, and scenario completion
      success rate and average scenario completion time, respectively. RESULTS: The
      implementation of MEDSI in our case study confirmed the view that the usability
      evaluation results of iconic GUIs were better than those of non-iconic GUIs in
      terms of Nielsen's heuristic evaluation, effectiveness and user satisfaction. For
      the whole sample, paired t-test scores indicated that there was a significant
      difference (p<0.01) between mean values of Nielsen's usability scores toward MEDS
      and MEDSI indicating that MEDSI was evaluated more favorably than MEDS. As for
      effectiveness of the prototypes, significant differences (p<0.01) were noted
      between MEDS and MEDSI in terms of both overall scenario completion success rate
      and average scenario completion time. Similarly, for the full sample of users
      independent sample t-test scores indicated that MEDSI was perceived significantly
      more favorable (p<0.01) than MEDS in terms of overall user satisfaction.
      CONCLUSION: The study provides two important contributions to the extant
      literature. First, it addresses a topic and methodology that serves potentially
      interesting to the biomedical informatics community. Drawing on good background
      information and appropriate context, it involves various aspects of usability
      testing. Another contribution of the study lies in its examination of two
      different prototypes during the design phase involving the target users.

PMID- 19755174
TI  - Preventive and curative glycoside kaempferol treatments attenuate the TH2-driven
      allergic airway disease.
AB  - Asthma is a chronic respiratory disease characterized by airway inflammation and
      airway hyperresponsiveness (AHR). One strategy to treat allergic diseases is the
      development of new drugs. Flavonoids are compounds derived from plants and are
      known to have antiallergic, anti-inflammatory, and antioxidant properties. To
      investigate whether the flavonoid kaempferol glycoside 3-O-[beta-d-glycopiranosil
      (1-->6)-alpha-l-ramnopiranosil]-7-O-alpha-l-ramnopiranosil-kaempferol (GRRK)
      would be capable of modulating allergic airway disease (AAD) either as a
      preventive (GRRK P) or curative (GRRK C) treatment in an experimental model of
      asthma. At weekly intervals, BALB/c mice were subcutaneously (sc) sensitized
      twice with ovalbumin (OVA)/alum and challenged twice with OVA administered
      intranasally. To evaluate any preventive effect, GRRK was administered 1h (hour)
      before each OVA-sensitization and challenge, while to analyze the curative
      effect, mice were first sensitized with OVA, followed by GRRK given at day 18
      through 21. The onset of AAD was evaluated 24h after the last OVA challenge. Both
      treatments resulted in a dose-dependent reduction in total leukocyte and
      eosinophil counts in the bronchoalveolar lavage fluid (BAL). GRRK also decreased
      CD4(+), B220(+), MHC class II and CD40 molecule expressions in BAL cells.
      Histology and lung mechanic showed that GRRK suppressed mucus production and
      ameliorated the AHR induced by OVA challenge. Furthermore, GRRK impaired Th2
      cytokine production (IL-5 and IL-13) and did not induce a Th1 pattern of
      inflammation. These findings demonstrate that GRRK treatment before or after
      established allergic lung disease down-regulates key asthmatic features.
      Therefore, GRRK has a potential clinical use for the treatment of allergic
      asthma.

PMID- 19755175
TI  - Pharmacological characterization of anaphylaxis-like shock responses induced in
      mice by mannan and lipopolysaccharide.
AB  - Intravenous injection of lipopolysaccharide (LPS, a component of the Gram
      negative bacterial cell-surface) or mannan (Man, a component of the fungal cell
      surface) into mice reportedly induces anaphylaxis-like shock (ALS) via complement
      associated platelet degradation and platelet-activating factor (PAF),
      respectively. However, it is unclear whether PAF is involved in LPS-ALS or
      whether complements and/or platelets are involved in Man-ALS. Here, using
      preparations of Man from Saccharomyces cerevisiae and LPS from Klebsiella O3, we
      characterized and compared LPS-ALS and Man-ALS, with the following results. (1)
      ALS depended on mouse strain (ddY and BALB/c being highly responsive to Man and
      LPS, respectively), but not on Toll-like receptors 2 and 4. (2) In ddY mice, Man
      had little effect on platelets, K76 (C5a-inhibitor) did not prevent Man-ALS, and
      Man-ALS was augmented by prior platelet depletion. (3) CV-3988 (PAF antagonist)
      prevented Man-ALS, but not LPS-ALS. (4) LPS-ALS and Man-ALS were each augmented
      by prior injection of a muramyl dipeptide (MDP, a constituent abundant in the
      Gram-positive bacterial cell-surface), but prevented by prior macrophage
      depletion. (5) Co-administration of Man and LPS induced an augmented ALS in both
      ddY and BALB/c mice. These results indicate that (i) Man and LPS each induces ALS
      in mice in strain-dependent and macrophage-dependent (but not TLR-dependent) ways
      by stimulating a platelet-non-associated PAF pathway and a platelet-associated
      complement pathway, respectively, and (ii) these pathways are primed by MDP and
      exhibit mutually augmenting actions. Man-ALS and LPS-ALS may therefore serve as
      models for diseases involving augmentation by multiple or mixed infections.

PMID- 19755176
TI  - Perspectives--IJS issue no. 5, 2009.

PMID- 19755177
TI  - Proteomic analysis of lymphoid and haematopoietic neoplasms: there's more than
      biomarker discovery.
AB  - Lymphoid and haematopoietic neoplasms comprise a broad spectrum of different
      tumours, classified by the World Health Organization (WHO) on the basis of a
      combination of morphology, immunophenotypic, genetic and clinical features. Up to
      date for many of these neoplasms no single feature is regarded as a diagnostic
      gold standard. The application of proteomics to the study of neoplastic
      haematological diseases could help in the search for new diagnostic and
      prognostic markers, as well as in the development of new therapeutic strategies.
      In this review, we focus on the actual role of proteomics technologies in the
      study of neoplastic haematology. In particular, we analyse the results obtained
      in the field of body fluid, cell lines, and tissues proteomics, and discuss the
      improvement allowed by the new developed proteomic strategies, such as
      nanofluidic systems, analysis of formalin-fixed tissues, and quantitative high
      throughput techniques (SILAC, ICAT, iTRAQ).

PMID- 19755178
TI  - The stability of the circulating human proteome to variations in sample
      collection and handling procedures measured with an aptamer-based proteomics
      array.
AB  - Blood-based protein biomarkers hold great promise to advance medicine with
      applications that detect and diagnose diseases and aid in their treatment. We are
      developing such applications with our proteomics technology that combines high
      content with low limits of detection. Biomarker discovery relies heavily on
      archived blood sample collections. Blood is dynamic and changes with different
      sampling procedures potentially confounding biomarker studies. In order to better
      understand the effects of sampling procedures on the circulating proteome, we
      studied three sample collection variables commonly encountered in archived sample
      sets. These variables included (1) three different sample tube types, PPT plasma,
      SST serum, and Red Top serum, (2) the time from venipuncture to centrifugation,
      and (3) the time from centrifugation to freezing. We profiled 498 proteins for
      each of 240 samples and compared the results by ANOVA. The results found no
      significant variation in the measurements for most proteins (approximately 99%)
      when the two sample processing times tested were 2h or less, regardless of sample
      tube type. Even at the longest timepoints, 20 h, approximately 82% of the
      proteins, on average for the three collection tube types, showed no significant
      change. These results are encouraging for proteomic biomarker discovery.

PMID- 19755179
TI  - Pectin: structure and function - A special issue dedicated to Professor Walter
      Pilnik.

PMID- 19755180
TI  - Pectin: structure and function - A special issue dedicated to Professor Walter
      Pilnik. Editorial.

PMID- 19755181
TI  - Chapter 1: The physiological role of lysyl tRNA synthetase in the immune system.
AB  - Lysyl tRNA synthetase (LysRS) is an aminoacyl-tRNA synthetase (AaRS). This group
      of ancient proteins, known for their critical role in translation, was found in
      recent years to function in a variety of other roles. Besides its enzymatic
      activity in aminoacylation of tRNA, LysRS can produce dinucleotide diadenosine
      tetraphosphate (Ap(4)A). Intracellularly, it is found mainly in the cytoplasm as
      a part of a multisynthetase complex where it interacts with several proteins,
      most notably AIMP2. Besides its role in translation it has been demonstrated that
      LysRS can act as a cytokine-like molecule, secreted by cells and having distinct
      effects on macrophages. Moreover, LysRS can bind to the transcription factors
      USF2 and MITF and can influence their transcriptional activities following
      immunological stimulation of mast cells. In this review, we focus on the
      nontranslational functions of LysRS related to the immune system. We begin with a
      short discussion of "gene sharing," proceed to a description of its structural
      and enzymatic function and then describe some of the in vivo functions of this
      enzyme.

PMID- 19755182
TI  - Chapter 2: Kill the bacteria...and also their messengers?
AB  - We consider here a previously neglected aspect of recovery from infectious
      diseases: how animals dispose of the dead microbes in their tissues. For one of
      the most important disease-causing microorganisms, Gram-negative bacteria, there
      is now evidence that the host catabolism of a key microbial molecule is essential
      for full recovery. As might be expected, it is the same bacterial molecule that
      animals sense to detect the presence of Gram-negative bacteria in their tissues,
      the cell wall lipopolysaccharide (LPS). Here, we discuss current knowledge about
      LPS sensing with emphasis on the host enzyme that inactivates this microbial
      "messenger" molecule. We also consider the possibility that the rate at which
      stimulatory microbial molecules undergo inactivation may influence the duration
      and severity of diseases caused by other infectious agents.

PMID- 19755183
TI  - Chapter 3: Role of SOCS in allergic and innate immune responses.
AB  - Cytokines are powerful mediators of the immune response that, following initial
      release by components of the innate system, drive effector functions as well as
      stimulate the additional arms of the response. Their individual functions are
      diverse, with stimulatory and inhibitory actions, with the resultant systemic
      immune response a summation of these actions. The frequently opposing effects of
      cytokines determine that the blockade of one results in the functional
      augmentation of the other. Thus, the differential regulation of cytokines
      profoundly influences the character of the immune response. The suppressor of
      cytokine signaling proteins are a family of molecules pivotal to this critical
      regulation. In this review, we will discuss their structural components and
      functions and our understanding of their impact on the systemic immune response.

PMID- 19755185
TI  - Guidelines for the care of heart failure patients.

PMID- 19755184
TI  - Chapter 4: Multitasking by exploitation of intracellular transport functions the
      many faces of FcRn.
AB  - The MHC Class I-related receptor, FcRn, transports antibodies of the
      immunoglobulin G (IgG) class within and across a diverse array of different cell
      types. Through this transport, FcRn serves multiple roles throughout adult life
      that extend well beyond its earlier defined function of transcytosing IgGs from
      mother to offspring. These roles include the maintenance of IgG levels and the
      delivery of antigen in the form of immune complexes to degradative compartments
      within cells. Recent studies have led to significant advances in knowledge of the
      intracellular trafficking of FcRn and (engineered) IgGs at both the molecular and
      cellular levels. The engineering of FcRn-IgG (or Fc) interactions to generate
      antibodies of increased longevity represents an area of active interest,
      particularly in the light of the expanding use of antibodies in therapy. The
      strict pH dependence of FcRn-IgG interactions, with binding at pH 6 that becomes
      essentially undetectable as near neutral pH is approached, is essential for
      efficient transport. The requirement for retention of low affinity at near
      neutral pH increases the complexity of engineering antibodies for increased half
      life. Conversely, engineered IgGs that have gained significant binding for FcRn
      at this pH can be potent inhibitors of FcRn that lower endogenous IgG levels and
      have multiple potential uses as therapeutics. In addition, molecular studies of
      FcRn-IgG interactions indicate that mice have limitations as preclinical models
      for FcRn function, primarily due to cross-species differences in FcRn-binding
      specificity.

PMID- 19755186
TI  - Influence of a symptom management telehealth intervention on older adults' early
      recovery outcomes after coronary artery bypass surgery.
AB  - OBJECTIVE: The study objective was to examine the effect of a symptom management
      (SM) telehealth intervention on physical activity and functioning and to describe
      the health care use of older adult patients (aged > 65 years) after coronary
      artery bypass surgery (CABS) by group (SM intervention group and usual care
      group). METHODS: A randomized clinical trial design was used. The study was
      conducted in 4 Midwestern tertiary hospitals. The 6-week SM telehealth
      intervention was delivered by the Health Buddy (Health Hero Network, Palo Alto,
      CA). Measures included Modified 7-Day Activity Interview, RT3 accelerometer
      (Stayhealthy, Inc, Monrovia, CA), physical activity and exercise diary, Medical
      Outcomes Study Short-Form 36, and subjects' self-report and provider records of
      health care use. Follow-up times were 3 and 6 weeks and 3 and 6 months after
      CABS. RESULTS: Subjects (N = 232) had a mean age of 71.2 (+4.7) years. There were
      no significant interactions using repeated-measures analyses of covariance. There
      was a significant group effect for average kilocalories/kilogram/day of estimated
      energy expenditure as measured by the RT3 accelerometer, with the usual care
      group having a higher estimated energy expenditure. Both groups had significant
      improvements over time for role-physical, vitality, and mental functioning. Both
      groups had similar health care use. CONCLUSION: Subjects were able to return to
      preoperative levels of functioning between 3 and 6 months after CABS and to
      increase their physical activity over reported preoperative levels of activity.
      Further study of those patients undergoing CABS who could derive the most benefit
      from the SM intervention is warranted.

PMID- 19755187
TI  - Sensations during removal of epicardial pacing wires after coronary artery bypass
      graft surgery.
AB  - BACKGROUND: One procedure that is commonly performed after coronary artery bypass
      graft surgery is removal of epicardial pacing wires (EPWs). Currently, there is a
      paucity of information regarding the sensations experienced by patients during
      this procedure. OBJECTIVE: To determine the sensations commonly reported by
      patients during EPW removal. METHODS: A secondary analysis was performed on data
      sets from 2 previous studies to determine the sensations commonly experienced by
      patients during EPW removal. The sample consisted of 144 subjects from 2 teaching
      hospitals. RESULTS: The most commonly reported sensation during EPW removal was a
      "mild to moderate pulling" sensation. CONCLUSION: This secondary analysis
      provides important information regarding the sensations most commonly reported by
      patients during EPW removal. This sensory information could be incorporated into
      a psycho-educational information intervention to prepare patients for EPW
      removal.

PMID- 19755188
TI  - Depressed patients understand heart failure prognosis but not how to control it.
AB  - BACKGROUND: Depression prevalence in patients with heart failure (HF) is 21% to
      42%. Conceptual illness beliefs that patients have about HF may be associated
      with depression. METHODS: We examined whether accuracy of illness beliefs was
      associated with depression. Illness belief scores were compared with depression
      severity, and multivariable analyses were performed to determine factors that
      were independently associated with depression. RESULTS: In 219 elderly patients
      with HF, depression prevalence was 47%. Accuracy of illness beliefs was
      associated with depression (r = .224; P = .049), due solely to accuracy of
      beliefs about consequences of HF (P = .005). Beliefs about how to control HF
      remained stable as depression severity increased. After controlling for
      significant univariable factors, mean illness belief and consequence scores
      remained associated with depression. CONCLUSION: In this sample, accuracy of
      beliefs about HF consequences increased but beliefs about how to control HF
      remained unchanged as depression severity worsened. This combination of HF
      beliefs may influence coping through self-care behaviors.

PMID- 19755189
TI  - Self-care and depression in patients with chronic heart failure.
AB  - BACKGROUND: Although chronic heart failure (CHF) is often complicated by comorbid
      depression and poor self-care, little is known about their specific association
      in patients with CHF. OBJECTIVE: To investigate self-care behavior among patients
      with CHF with different degrees of depression severity. METHODS: A total of 287
      patients with documented CHF, New York Heart Association functional class II to
      IV, completed the European Heart Failure Self-Care Behavior Scale. The Structured
      Clinical Interview for DSM (SCID) IV served as the criterion standard for the
      presence of a depressive disorder. RESULTS: Analyses of covariance and linear
      regression analyses revealed that patients with CHF with minor depression
      reported significantly lower levels of self-care than patients with major
      depression (P = .003) and nondepressed patients (P = .014). In addition to minor
      depression, age (P < or = .001), multimorbidity (P = .01), left ventricular
      ejection fraction (P = .001), and family status (P = .01) were determinants of
      self-care. CONCLUSION: Our results demonstrate that patients with CHF with minor
      depression and not major depression are at higher risk for poor self-care and its
      resulting consequences, such as symptom deterioration and frequent
      hospitalization.

PMID- 19755190
TI  - Adherence to self-care behavior and factors related to this behavior among
      patients with heart failure in Japan.
AB  - BACKGROUND: Adherence to self-care behavior is important for patients with heart
      failure (HF) to prevent exacerbation of HF. The aim of this study was to evaluate
      adherence, identify associated factors, and clarify the impact of previous HF
      hospitalizations on adherence in outpatients with HF. METHODS: A total of 116
      outpatients completed a questionnaire, including the Japanese version of the
      European Heart Failure Self-Care Behavior Scale, to assess adherence. RESULTS:
      Regardless of previous hospitalizations, adherence to seek help if HF worsened
      was poor. Multivariate analysis adjusted for age and brain natriuretic peptide
      showed that diabetes mellitus and being employed were independent predictors of
      poorer adherence to self-care behavior (P = .03, P = .02, respectively), but the
      experience of previous HF hospitalizations was not a predictor. CONCLUSIONS: Self
      care strategies for HF should target patients with diabetes mellitus and employed
      patients. Further study is necessary to develop effective programs for such
      patients.

PMID- 19755191
TI  - Testing a model of patient characteristics, psychologic status, and cognitive
      function as predictors of self-care in persons with chronic heart failure.
AB  - OBJECTIVE: Self-care is a key component in the management of chronic heart
      failure (CHF). Yet there are many barriers that interfere with a patient's
      ability to undertake self-care. The primary aim of the study was to test a
      conceptual model of determinants of CHF self-care. Specifically, we hypothesized
      that cognitive function and depressive symptoms would predict CHF self-care.
      METHODS: Fifty consecutive patients hospitalized with CHF were assessed for self
      care (Self-Care of Heart Failure Index), cognitive function (Mini Mental State
      Exam), and depressive symptoms (Cardiac Depression Scale) during their index
      hospital admission. Other factors thought to influence self-care were tested in
      the model: age, gender, social isolation, self-care confidence, and comorbid
      illnesses. Multiple regression was used to test the model and to identify
      significant individual determinants of self-care maintenance and management.
      RESULTS: The model of 7 variables explained 39% (F [7, 42] 3.80; P = .003) of the
      variance in self-care maintenance and 38% (F [7, 42] 3.73; P = .003) of the
      variance in self-care management. Only 2 variables contributed significantly to
      the variance in self-care maintenance: age (P < .01) and moderate-to-severe
      comorbidity (P < .05). Four variables contributed significantly to the variance
      in self-care management: gender (P < .05), moderate-to-severe comorbidity (P <
      .05), depression (P < .05), and self-care confidence (P < .01). When cognitive
      function was removed from the models, the model explained less of the variance in
      self-care maintenance (35%) (F [6, 43] 3.91; P = .003) and management (34%) (F
      [6, 43] 3.71; P = .005). CONCLUSION: Although cognitive function added to the
      model in predicting both self-care maintenance and management, it was not a
      significant predictor of CHF self-care compared with other modifiable and
      nonmodifiable factors. Depression explained only self-care management.

PMID- 19755192
TI  - Factors influencing depression in adolescents with congenital heart disease.
AB  - OBJECTIVE: This study was designed to identify variables associated with
      depression in adolescents who underwent operation for congenital heart disease
      (CHD). METHODS: Data were collected from 231 adolescents, aged 13 to 18 years
      with CHD, during outpatient clinic follow-up after open heart surgery in 3 major
      cardiac centers in Korea. Adolescents completed measures of resilience,
      depression, and parental attitude. Their New York Heart Association functional
      class, CHD functional index, and noninvasive saturation of arterial oxygen were
      also measured. RESULTS: There were significantly positive relations between
      depression and the 3 variables: older age, worse New York Heart Association
      functional class, and higher CHD functional index. Negative relations were found
      between depression and higher saturation of arterial oxygen, higher academic
      achievements, affectionate parental attitude, and higher resilience. The multiple
      regression analysis also showed that 62% of the variance in depression in
      adolescents with CHD could be explained by resilience and parental attitude.
      CONCLUSION: This study demonstrated that adolescents with higher resilience and
      an affectionate parent were less depressed.

PMID- 19755193
TI  - Reasons for readmission in heart failure: Perspectives of patients, caregivers,
      cardiologists, and heart failure nurses.
AB  - OBJECTIVE: Despite efforts to improve outcomes in heart failure (HF), readmission
      rates remain relatively high. Reasons for readmission from different perspectives
      (patient, caregiver, health care providers) may help to optimize the future
      management of patients with HF. The aims of this study are to 1) gain insight
      into reasons for HF readmission from the perspective of patients, caregivers,
      cardiologists, and HF nurses; 2) examine similarities and differences in
      perspectives on the reason for an HF readmission, and 3) describe possibilities
      to prevent an HF readmission from different perspectives. METHODS AND RESULTS:
      Data on reasons for readmission were collected on 173 readmissions. Perspectives
      of patients, caregivers, cardiologists, and HF nurses were collected by interview
      and questionnaire. Worsening HF as the sole reason for readmission was reported
      most often; however, 36% of caregivers, 56% of patients, and 63% to 65% of health
      care providers indicated that other factors, such as comorbidity, nonadherence,
      and nonoptimal medication, were important contributing factors. In only 34% of
      readmissions, patients and their caregivers agreed with health care providers on
      the underlying reason. Respondents reported that 23% to 31% of the readmissions
      could probably have been prevented if adherence were higher, patients requested
      help earlier, and adequate multidisciplinary professional help were available.
      CONCLUSION: To prevent future readmissions of patients with HF, it is important
      to fully understand the reasons for readmission by gaining insight on the reason
      for readmission from different perspectives. Also, we may need another approach
      to prevent adverse outcomes in which other medical problems and new strategies to
      improve adherence have to be considered.

PMID- 19755194
TI  - Placement of the nebulizer before the humidifier during mechanical ventilation:
      Effect on aerosol delivery.
AB  - BACKGROUND: Therapeutic aerosols are commonly used in mechanically ventilated
      patients. The position of the nebulizer in the ventilator circuit and the
      humidification of inhaled gases can influence the efficiency of aerosol delivery.
      We evaluated the effect of nebulizer position on the pulmonary bioavailability of
      nebulized ipratropium in ventilated patients without known preexisting
      respiratory disease. METHODS: The study included 38 mechanically ventilated and
      sedated patients after open heart surgery. Ipratropium (500 microg) was delivered
      by an ultrasonic nebulizer. Patients were randomized into 2 groups: the nebulizer
      positioned before the heat humidification system (group 1, n = 19) or at the end
      of the inspiratory limb before the Y-piece (group 2, n = 19). The amount of
      ipratropium in the urine collected during the 4 hours after drug administration
      was measured by mass spectrometry. RESULTS: There were no statistically
      significant differences in tidal volume or respiratory rate between groups. There
      were no significant differences between the 2 groups in the amount of drug
      excreted (group 1 vs 2: 13,237 +/- 2313 pg/mL vs 15,529 +/- 3204 pg/mL) or in
      pulmonary bioavailability (.9% +/- .1% vs 1.1% +/- .2%). CONCLUSION: The position
      of the nebulizer in the ventilatory circuit had no effect on the pulmonary
      bioavailability of ipratropium.

PMID- 19755195
TI  - Sudden onset of chest pain associated with PR-segment depression in ECG.

PMID- 19755196
TI  - Mycoplasma pneumoniae community-acquired pneumonia (CAP) in the elderly:
      Diagnostic significance of acute thrombocytosis.
AB  - The most common cause of nonzoonotic atypical community-acquired pneumonia (CAP)
      is Mycoplasma pneumoniae. M. pneumoniae CAP is most common in young adults but
      may occur at any age. Like other atypical CAPs, M. pneumoniae is associated with
      a characteristic pattern of extrapulmonary organ involvement and nonspecific
      laboratory tests. M. pneumoniae CAP is frequently accompanied by gastrointestinal
      manifestations (eg, loose stools/diarrhea), nonexudative pharyngitis, or skin
      involvement (ie, erythemamultiforme). Central nervous system involvement with M.
      pneumoniae is rare and accompanied by highly elevated cold agglutinin titers.
      Cardiac, hepatic, and renal involvement are not features of M. pneumoniae CAP.
      Because M. pneumoniae CAP is most frequent in ambulatory young adults, it is an
      easily overlooked diagnosis in elderly patients hospitalized with CAP. The
      hallmark clinical finding of M. pneumoniae CAP is protracted nonproductive cough.
      The characteristic nonspecific laboratory test finding uniquely associated with
      M. pneumoniae CAP is elevated cold agglutinin titers. Seventy-five percent of
      patients with M. pneumoniae infection have elevated cold agglutinin titers.
      However, the absence of elevated cold agglutinin titers does not argue against
      the diagnosis of M. pneumoniae. If cold agglutinins are present in a patient with
      CAP, the higher the cold agglutinin titer is (>1:64), the more likely the cold
      agglutinins are due to M. pneumoniae. Q fever is the only other atypical CAP that
      is rarely associated with cold agglutinins. We present a hospitalized patient
      with CAP in whom all microbiologic and serologic diagnostic test results were
      negative during the first week of her hospitalization. M. pneumoniae CAP was not
      suspected because of her age. Her initial M. pneumoniae immunoglobulin-M and cold
      agglutinin titers were negative. During the second week of hospitalization, an
      increased platelet count was noted. It is a common misconception that acute
      thrombocytosis is an acute phase reactant. Her acute thrombocytosis increased and
      persisted. The diagnostic clue to the cause of this hospitalized patient with CAP
      was acute thrombocytosis. In a patient with CAP, acute thrombocytosis is usually
      associated with Q fever pneumonia and less commonly with M. pneumoniae. If Q
      fever can be excluded on the basis of a recent/proximate zoonotic vector contact
      history, then acute thrombocytosis is an important clue to M. pneumoniae CAP.
      Acute thrombocytosis due to M. pneumoniae and Q fever occurs during weeks 1 and 2
      of the infection. In patients with CAP, acute thrombocytosis that occurs during
      weeks 1 and 2 of the illness should suggest M. pneumoniae in patients without
      recent zoonotic vector contact history.

PMID- 19755197
TI  - Fever of unknown origin (FUO) caused by Kikuchi's disease mimicking lymphoma.
AB  - Fever of unknown origin (FUO) refers to infectious, neoplastic, or
      rheumatic/inflammatory disorders that present with fevers of 101 degrees F or
      greater for 3 weeks and that remain undiagnosed after an intensive in-hospital or
      outpatient workup. The noninfectious causes of FUO in adults are most often
      lymphomas or rheumatic/inflammatory disorders. Among the rare causes of
      rheumatic/inflammatory FUOs is Kikuchi's disease. Kikuchi's disease (Kikuchi
      Fujimoto disease) is also known as histiocytic necrotizing lymphadenitis, a
      benign, self-limited disorder usually in middle-aged women of Asian descent.
      Cervical adenopathy is typical and often accompanied by leukopenia. In middle
      aged adults patients presenting with an FUO, the presence of otherwise
      unexplained cervical adenopathy should suggest the possibility of lymphoma or,
      rarely, Kikuchi's disease.

PMID- 19755198
TI  - Effects of left ventricular lead positions and coronary venous microanatomy on
      cardiac pacing parameters.
AB  - We describe effects of pacing lead position and cardiac microanatomy on
      electrical pacing parameters. Passive fixation transvenous pacing leads were
      implanted in anterior interventricular veins in isolated swine hearts (n = 6).
      Electrical pacing parameters were measured in 3 implant positions (5 implant
      sites each): touching myocardial side of venous wall, not touching venous wall,
      and touching epicardial side of venous wall. After perfusion fixing hearts, veins
      were sectioned perpendicular to vein's length from base to apex. Slides were
      prepared and analyzed for measurement of vein wall thickness/circumference, and
      distances between vein walls and myocardium. Average pacing thresholds were
      greater when pacing leads were free-floating (5.45 +/- 3.29 V) or oriented in
      epicardial positions (6.81 +/- 2.96 V) compared with myocardial positions (3.79
      +/- 3.46 V; P = not significant). Vein circumferences were significantly larger
      in basal regions (8.31 +/- 2.28 mm) compared with mid (6.90 +/- 1.46 mm) and
      apical (6.40 +/- 1.92 mm) regions (P < .05). Variability in pacing thresholds and
      impedances indicates that pacing lead placement in left ventricular coronary
      veins significantly affects electrical pacing parameters.

PMID- 19755199
TI  - Fluorodeoxyglucose positron emission tomography (FDG-PET) is useful in the
      diagnosis of neurosarcoidosis.
AB  - A 45-year-old man presented with a progressive transverse spinal cord syndrome.
      MRI scanning revealed bitemporal and multiple spinal lesions with significant
      enhancement after gadolinium administration mimicking an acute disseminated
      encephalomyelitis. CSF analyses showed a lymphocytic pleocytosis. After treatment
      with high dose steroids clinical improvement was observed with a secondary
      decline shortly thereafter. MRI rescanning showed no remarkable alterations of
      the lesions. Further diagnostic work-up included a fluorodeoxyglucose positron
      emission tomography (FDG-PET) of the whole body to search for occult inflammation
      or neoplasia. The FDG-PET showed hypermetabolic foci corresponding to the lesions
      on MRI and additionally increased uptake in mediastinal and pulmonary hilar lymph
      nodes. A mediastinal lymph node was biopsied. Pathology was consistent with the
      diagnosis of sarcoidosis. The usual diagnostical tools to evaluate a sarcoidosis,
      such as serum angiotensin converting enzyme (ACE) and computed tomography of the
      chest were performed initially and revealed no pathological results. Therefore,
      in this case FDG-PET was crucial for the diagnostic work-up leading to an
      accessible inflammatory lesion outside the CNS for biopsy and the final diagnosis
      of sarcoidosis.

PMID- 19755200
TI  - Restless Legs Syndrome (RLS) and Parkinson's disease (PD)-related disorders or
      different entities?
AB  - The relationship between Restless Legs Syndrome (RLS) and Parkinson's disease
      (PD) is still controversial. Most genetic, pathological, and imaging data argue
      against a close association of these two disorders. Still, many studies reported
      an increased prevalence of RLS in PD patients. These studies are difficult to
      interpret because the current diagnostic criteria for RLS have not been validated
      in PD patients. Although many PD patients suffer from motor restlessness due to
      parkinsonism and may thus mimic RLS, the risk for (secondary) RLS in PD patients
      is probably slightly increased. This review provides an overview of the current
      pertinent literature and discusses the possible association between RLS and PD.

PMID- 19755201
TI  - Single residue deletions along the length of the influenza HA fusion peptide lead
      to inhibition of membrane fusion function.
AB  - A panel of eight single amino acid deletion mutants was generated within the
      first 24 residues of the fusion peptide domain of the of the hemagglutinin (HA)
      of A/Aichi/2/68 influenza A virus (H3N2 subtype). The mutant HAs were analyzed
      for folding, cell surface transport, cleavage activation, capacity to undergo
      acid-induced conformational changes, and membrane fusion activity. We found that
      the mutant DeltaF24, at the C-terminal end of the fusion peptide, was expressed
      in a non-native conformation, whereas all other deletion mutants were transported
      to the cell surface and could be cleaved into HA1 and HA2 to activate membrane
      fusion potential. Furthermore, upon acidification these cleaved HAs were able to
      undergo the characteristic structural rearrangements that are required for
      fusion. Despite this, all mutants were inhibited for fusion activity based on two
      separate assays. The results indicate that the mutant fusion peptide domains
      associate with target membranes in a non-functional fashion, and suggest that
      structural features along the length of the fusion peptide are likely to be
      relevant for optimal membrane fusion activity.

PMID- 19755202
TI  - Distinct neuronal oscillatory responses between patients with bipolar and
      unipolar disorders: a magnetoencephalographic study.
AB  - BACKGROUND: Bipolar disorder (BD) and major depressive disorder (MDD) have
      distinct pathophysiologies but similar depressive appearances. The present study
      aimed at the differentiation of the brain responses between BD and MDD patients.
      We hypothesized that different affective disorder patients may have distinct
      patterns of oscillatory cortical activities in response to negative emotional
      stimuli. METHODS: Twenty BD patients, twenty MDD patients, and twenty age- and
      gender-matched healthy normal subjects were recruited. We adopted an implicit
      emotional task with facial image stimuli. The acquired event-related
      magnetoencephalographic signals were processed by the time-frequency analysis and
      beamformer-based source imaging techniques followed by statistical inference.
      RESULTS: We found that there were gamma oscillation decreases in the frontal
      regions of both BD and MDD patients, gamma oscillation increases in the bilateral
      temporal regions of MDD, and alpha-beta rhythm increases in BD patients. Relative
      to the cortical activation in the control group, the BD patients displayed more
      widely increased oscillatory activities over the fronto-parieto-occipital regions
      than MDD patients. CONCLUSIONS: Our results demonstrate the distinct
      neuropathological patterns of emotional responses in BD and MDD patients. The
      findings suggest that the dysfunction of emotion regulation in BD may result from
      the increased sensitivity to emotionally salient information, implicating the
      potential cause of the emotion lability. The present study also suggests that the
      implicit emotional task is an effective approach to differentiate bipolar from
      unipolar disorders and their distinct neuropathological patterns to emotional
      stimuli may provide objective and quantitative measures for potential diagnostic
      significance.

PMID- 19755203
TI  - Prognosis in patients with severe heart failure referred for heart
      transplantation--POLKARD-HF 2003-2007.
AB  - POLKARD-HF study was a prospective registry of patients, referred for the heart
      transplantation. The registry collected data on factors influencing the prognosis
      of patients. The death or the emergency heart transplantation (UNOS status 1) was
      assumed as the endpoint in the distant observation. 983 patients (88% men, mean
      age <50) with severe heart failure (HF), referred to 4 centers were analyzed. The
      average period of observation was 601 days (1 to 1462 days). The Kaplan-Meier
      probability of surviving 1 year without urgent heart transplantation was 80%, 2
      years 70%, and 3 years 67%. HF etiology was dilated cardiomyopathy in 49.4% and
      ischemic cardiomyopathy in 43.2%. There was only a trend in favor of survival of
      patients with dilated cardiomyopathy (p=0.1). Prognosis in patients with NYHA
      classes II and III did not differ but in NYHA IV, was significantly worse. The
      probability of 6-month survival was 60%, 1-year--50%, and 3-year--40%. In Kaplan
      Meier analysis survival was worse for pts with pulmonary artery systolic pressure
      >=50 mmHg, pulmonary capillary pressure >=25 mmHg, left ventricular ejection
      fraction <=17%, functional NYHA class IV, systemic systolic arterial pressure
      <=90 mmHg, hsCRP>=6.5 mg/L, NTpro-BNP>=4302, Na serum level<=135 mEq/L,
      BMI<=23.8, and HFSS<=7.19. When only biochemistry parameters were analyzed using
      ROC, sodium plasma levels <=135 mEq/L alone gave ROC 58.3% and inclusion of NTpro
      BNP>=4302 pg/mL into the model, increased the predictive value up to 61.2%.

PMID- 19755204
TI  - Combined effect of MAP and active compounds on fresh blue fish burger.
AB  - The combined effects of three essential oils [thymol, lemon extract and
      grapefruit seed extract (GFSE)] and modified atmosphere packaging conditions
      (MAP) on quality retention of blue fish burgers was studied and discussed. In
      particular, samples were packaged in air and in three different gas mix
      compositions: 30:40:30 O(2):CO(2):N(2), 50:50 O(2):CO(2) and 5:95 O(2):CO(2).
      During a 28-day storage period at 4 degrees C, the nutritional, microbiological
      and sensorial quality of the packed products was assessed. The potential
      development of biogenic amines was also evaluated. The obtained results highlight
      the possibility to improve the microbial quality of blue fish burgers by using
      very small amount of thymol (110ppm), GFSE (100ppm) and lemon extract (120ppm) in
      combination with MAP. Based primarily on microbiological results, the combined
      use of the tested natural preservatives and a packaging system characterized by a
      high CO(2)-concentration, was able to guarantee the microbial acceptability of
      fish burgers until the 28th day of storage at 4 degrees C. On the other hand,
      results from sensory analyses showed that sensorial quality was the sub-index
      that limited the burgers shelf life (to about 22-23days), even if the proposed
      strategy was also effective in minimizing the sensory quality loss of the product
      having no effect on its nutritional quality.

PMID- 19755205
TI  - Registering spherical navigators with spherical harmonic expansions to measure
      three-dimensional rotations in magnetic resonance imaging.
AB  - Subject motion remains a challenging problem to overcome in clinical and research
      applications of magnetic resonance imaging (MRI). Subject motion degrades the
      quality of MR images and the integrity of experimental data. A promising method
      to correct for subject motion in MRI is the spherical navigator (SNAV) echo.
      Spherical navigators acquire k-space data on the surface of a sphere in order to
      measure three-dimensional (3D) rigid-body motion. Analysis begins by registering
      the magnitude of two SNAVs to determine the 3D rotation between them. Several
      different methods to register SNAV data exist, each with specific capabilities
      and limitations. In this study, we assessed the accuracy, precision and
      computational requirements of measuring rotations about all three coordinate axes
      by correlating the spherical harmonic expansions of SNAV data. We compare the
      results of this technique to previous SNAV studies and show that, although
      computationally expensive, the spherical harmonic technique is a highly accurate,
      precise and robust method to register SNAVs and detect 3D rotations in MRI. A key
      advantage to the spherical harmonic technique is the ability to optimize the
      accuracy, precision, processing time and memory requirements by adjusting
      parameters used in the registration. While present developments are aimed at
      improving the programming efficiency and memory handling of the algorithm, this
      registration technique is currently well suited for retrospective motion
      correction applications, such as removing motion-related image artifacts and
      aligning slices within a high-resolution 3D volume.

PMID- 19755206
TI  - Introduction and thoughts on the fourth issue of EuroIntervention.

PMID- 19755207
TI  - Intracardiac echocardiography during interventional procedures.

PMID- 19755208
TI  - Percutaneous coronary interventions in Europe 1992-2003.
AB  - AIMS: The purpose of this registry is to collect data on trends in interventional
      cardiology within Europe. Special interest focuses on relative increases and
      ratios in newer revascularization approaches and its distribution in different
      regions in Europe. We report the data of the year 2003 and give an overview of
      the development of coronary interventions since 1992, when the first data
      collection was performed. METHODS AND RESULTS: Questionnaires were distributed
      yearly to delegates of all national societies of cardiology represented in the
      European Society of Cardiology to collect the case numbers of all local
      institutions and operators. The overall numbers of coronary angiographies
      increased from 1992 to 2003 from 684,000 to 1,993,000 (from 1,250 to 3,500 per
      million inhabitants). The respective numbers for percutaneous coronary
      interventions (PCI-coronary angioplasty) and coronary stenting procedures
      increased from 184,000 to 733,000 (from 335 to 1,300) and from 3,000 to 610,000
      (from 5 to 1,100), respectively. Germany has been the most active country for the
      past years with 653,000 angiographies (7,800), 222,000 angioplasties (2,500), and
      180,000 stenting procedures (2,200) in 2003. The indication has shifted towards
      acute coronary syndromes, as demonstrated by raising rates of interventions for
      acute myocardial infarction over the last decade. The procedures are more readily
      performed and safer, as shown by increasing rate of "ad hoc" PCI and decreasing
      need for emergency coronary artery bypass surgery (CABG). In 2003, use of drug
      eluting stents had further increased. However, an enormous variability is
      reported with the highest rate in Portugal (55%). CONCLUSION: Interventional
      cardiology in Europe is still expanding, mainly but not exclusively due to rapid
      growth in the eastern European countries. A number of new coronary
      revascularization procedures introduced over the years have all but disappeared.
      Only stenting has experienced an exponential growth. The same can be forecast for
      drug-eluting stenting.

PMID- 19755209
TI  - The first stent in man?

PMID- 19755210
TI  - Arterial scaffolding: from concept to standard of care.

PMID- 19755211
TI  - Prospective non-randomized multi-centre evaluation of the non-polymer based
      ACHIEVE Paclitaxel Eluting Coronary Stent System in treatment of lesions with
      high risk of revascularization due to restenosis: the DELIVER II study.
AB  - BACKGROUND: The ACHIEVE Paclitaxel Eluting Coronary Stent System (CSS) is a non
      polymeric paclitaxel coated stent loaded with a dose density of 3.0 microg/mm2
      stent surface area. DELIVER II set out to evaluate the use of this stent in the
      treatment of patients with coronary lesions with a higher risk of
      revascularization including chronic total or sub-total occlusion, small vessel,
      bifurcated, and long lesions, multivessel disease, and restenotic lesions.
      METHODS: DELIVER II was a prospective, non-randomized, single-arm, multi-centre
      study. A total of 1531 patients with 1986 lesions were enrolled at 86 sites
      worldwide. The primary endpoint was target lesion revascularization (TLR) rate at
      six months follow-up. The lesion subsets were comprised of 28.5% restenotic
      lesions, 16.5% chronic total or subtotal occlusions, 29.0% bifurcation lesions,
      37.4% small vessels and 16.6% long lesions. RESULTS: The Target Lesion
      Revascularization (TLR) rate (intent-to-treat) at 180 days was 8.2% (156/1909).
      The MACE rate for the overall per-protocol population was 3.6% (47/1310) at 30
      days, 13.0% (167/1287) at 180 days, and in a sub-set of 500 patients, 20.5%
      (84/409) at 365 days. Multivariable logistic regression analysis identified that
      the factors leading to higher risk of revascularization were left anterior
      descending artery lesions, restenotic lesions, the post-procedural minimum
      luminal diameter, total stent length and number of diseased vessels. CONCLUSION:
      DELIVER II demonstrated comparatively low rates of TLR and MACE for the ACHIEVE
      Paclitaxel Eluting CSS in high risk patients. In addition, this registry helped
      to identify risk factors leading to an increased risk of revascularization in
      difficult-to-treat patient groups.

PMID- 19755212
TI  - Impact of drug eluting stents on target vessel revascularization. A report from
      the Western Denmark heart registry from 2000 to 2004.
AB  - BACKGROUND: Limited information is available on target lesion revascularization
      (TLR) after percutaneous coronary intervention (PCI) in unselected patients at
      the beginning of the drug eluting stent (DES) era. METHODS AND RESULTS: From
      January 2000 to September 2004 data from all PCI procedures in Western Denmark
      were recorded in the Western Danish Heart Registry. A total of 24,701 lesions
      were treated in 15,542 patients. Lesion length, stent length, frequency of
      complex lesions and age increased from 2000 to 2004. The use of DES increased
      from 0% in 2000, 2001, 2002 to 34% in 2003 and 54.0% in 2004 of all stents used.
      The clinical driven TLR declined from 9.4% in 2000 to 5.4% in 2004. The use of
      DES (OR 0.60; 95% CI 0.39-0.92, p=0.018) and procedure year (OR 0.89; 95% CI 0.83
      0.97, p=0.008) and restenotic lesion (OR 1.51; 95% CI 1.18-1.93, p=0.001) were
      independent predictors of a TLR. Similar TLR rates were observed in diabetics
      (7.7%) and non-diabetic (7.0), p=NS. CONCLUSION: In unselected PCI patients the
      TLR rate declined from 2000 to 2004. The use of DES was an independent predictor
      of TLR.

PMID- 19755213
TI  - Clinical and angiographic outcome of paclitaxel-eluting stent implantation for
      unprotected left main coronary artery bifurcation narrowing.
AB  - AIMS: This study was designed to compare the clinical and angiographic outcomes
      of paclitaxel-eluting stent (PES) and bare metal stent (BMS) implantation for
      unprotected left main coronary artery (LMCA) bifurcation narrowing. METHODS AND
      RESULTS: From November 2003 to December 2004, the technique of kissing balloon
      followed by T provisional stenting was applied for distal left main coronary
      lesion in 49 consecutive patients with PES stents. Data from this group were
      compared to those from 57 patients treated with BMS during the previous year. The
      procedural success rate was 100% for both groups. There were no incidents of
      death, stent thrombosis, Q-wave myocardial infarction (MI), or emergent bypass
      surgery during hospitalization in either group. Despite less acute gain (2.18+/
      0.53 mm vs. 2.45+/-0.47 mm p= 0.078) in the PES group, PES patients showed a
      lower late lumen loss and a lower 8-month angiographic restenosis rate (6.1% vs.
      35.1% p<0.0001) versus the BMS group. At 10 months, the rate of freedom from
      death,MI, and target lesion revascularization was 95.9+/-2.8% in the PES group
      and 66.1+/-6.3% in the BMS group (p<0.0001). CONCLUSION: Paclitaxel-eluting stent
      implantation for unprotected LMCA bifurcation narrowing appears safe with regard
      to acute and midterm complications and is more effective in preventing restenosis
      compared to BMS implantation.

PMID- 19755214
TI  - Outcome of unprotected left main percutaneous coronary intervention in surgical
      low-risk, surgical high-risk, and acute myocardial infarction patients.
AB  - AIM: Percutaneous coronary intervention (PCI) of left main (LM) coronary artery
      stenosis may become an alternative to the standard therapy, coronary artery
      bypass graft surgery (CABG). The purpose of the present study was to describe the
      outcome after LM PCI in three cohorts of patients: patients with low surgical
      risk, patients with high surgical risk or patients considered inoperable, and
      patients with acute ST elevation MI. METHODS AND RESULTS: 104 consecutive
      patients who had LM PCI at the Department of Cardiology, Skejby University
      hospital between 1999 and 2004 were investigated. The patients were divided into
      three groups according to PCI indication and operability: surgical low risk
      patients and suitable lesions for PCI (n=27), poor CABG candidates (age > 80
      years, severe comorbidity or inoperability) (n=50), and patients presenting with
      AMI (n=27). In the three groups mean ages+/-SD were: 60+/-14, 76+/-9, and 68+/-12
      years, respectively. At thirty days follow-up the cumulative incidence of major
      adverse cardiac events (MACE); cardiac death, MI, or target lesion
      revascularization (95% CI) were 4 (1-24)%, 16 (8-30)%, and 41 (25-61)%,
      respectively. At 6 months the cumulative incidence of MACE were 4 (1-24)%, 27 (17
      43)%, and 41 (25-62)%. CONCLUSIONS: PCI of LM coronary artery stenosis can be
      performed with good outcome in patients with low surgical risk and with
      acceptable outcome in surgical high risk patients or patients considered
      inoperable. Patients with AMI and culprit lesion in the LM have a high mortality
      in the acute phase, but mid-term prognosis is good if the patient is successfully
      treated with PCI. This follow-up study underlines the importance of risk
      stratification in the heterogeneous group of patients undergoing LM PCI.

PMID- 19755215
TI  - Percutaneous treatment of bifurcated lesions: a simple approach with a single
      bare metal R stent provides favourable long term clinical results.
AB  - AIMS: Target lesion revascularization (TLR) rates of bifurcated lesions (BL)
      remain high, mainly due to side branch (SB) restenosis, even when drug-eluting
      stents (DES) are used. The aim of our study was to evaluate long-term clinical
      outcomes of a stepwise approach with single bare metal R stent implantation for
      BL. METHODS AND RESULTS: In 465 patients, PCI was performed using a double guide
      wire, single stent in main branch (MB), and angioplasty of the SB, aiming at an
      optimal angiographic result of the MB and an optimal functional result (TIMI 3
      flow) of the SB. 105 patients were treated for a true bifurcated lesion (TBL) and
      360 patients were treated for a lesion with involvement of a significant side
      branch (ISB). Procedural success was achieved in all TBL and in 99% of ISB. At 1
      year clinical follow-up, 8.6% treated for TBL had clinically driven TLR, 7.6%
      underwent repeat PCI, 1.0% underwent CABG. For patients treated for ISB, 13% had
      clinically driven TLR, 9.4% underwent repeat PCI, 3.6% CABG. 4 patients treated
      for TBL suffered non-fatal MI vs. 20 patients treated for ISB. Cardiac death
      occurred in 1.9% and 2.5 % respectively. CONCLUSION: A simple approach in the
      percutaneous treatment of BL using a single bare metal R stent results in good 1
      year clinical outcome comparable to the outcome reported following DES
      implantation.

PMID- 19755216
TI  - Myocardial repair by percutaneous cell transplantation of autologous skeletal
      myoblast as a stand alone procedure in post myocardial infarction chronic heart
      failure patients.
AB  - AIMS: In this first multicentre study we assessed the safety and efficacy of
      percutaneous transendocardial skeletal myoblast injection as a stand alone
      procedure in congestive heart failure patients. METHODS AND RESULTS: 15 patients
      (14 male), age 63+/-7 (Mean+/-SD), NYHA class 2-4 were injected with 216+/-119
      cells (81+/-19% Desmin+) using a NOGA or fluoroscopy guided injection catheter.
      The cells were injected in the scarred regions 6+/-4 years after myocardial
      infarction as a stand alone procedure. After treating the first 6 patients, the
      protocol was amended to require that remaining patients be fitted with an ICD
      prior to the cellular cardiomyoplasty procedure. Holter monitoring, ECG and ICD
      readings were obtained at multiple intervals. Stress echocardiography and LV
      angiography was performed at baseline, 3, 6 and 12 months post procedure.After 1
      year follow-up 13 patients were still alive. Patient # 6 died suddenly 9 days
      post procedure. Patient #15 (ICD patient) survived an electrical storm 12 days
      post procedure, but died 2 days later due to cardiogenic shock. Two non-ICD
      patients received an ICD because of observed ventricular arrhythmias. It remains
      unknown whether these events are directly related to the cell injections.LV
      ejection fraction (%) changed from 34.4+/-10.3 to 36.6+/-10.4 (baseline versus 12
      months FU, p=0.26). Wall motion score index improved both at rest (3.0+/-0.5 to
      2.7+/-0.7, p=0.049) and under low-dose dobutamine stress (2.8+/-0.4 to 2.5+/-0.6,
      p=0.07, baseline versus 12 months FU). CONCLUSION: Percutaneous autologous
      skeletal myoblast injection is feasible, resulting in wall motion and functional
      class improvement, but is potentially associated with an increased risk for
      ventricular arrhythmias. Randomised studies are needed, however, to further
      assess overall safety, efficacy and the potential for initial increased risk for
      arrhythmia following cell injection in these high-risk patients.

PMID- 19755217
TI  - Concurrent G-CSF and GM-CSF administration for the induction of bone marrow
      derived cell mobilization in patients with acute myocardial infarction: a pilot
      study evaluating feasibility, safety and efficacy.
AB  - AIMS: To verify feasibility and safety of bone marrow stem cells (BMC)
      mobilization in patients (pts) with acute myocardial infarction (AMI) and to
      monitor the clinical effects of BMC mobilization in terms of myocardial perfusion
      and function. METHODS AND RESULTS: Eight male pts (median age: 50.5 years)
      treated with a primary PTCA were enrolled. The mobilization regimen consisted of
      G-CSF 5 microg/kg/12 h from day 0 to day +2 and GM-CSF 2.5 microg/kg/24 h. All
      pts underwent coronary angiography, intracoronary doppler flow study,
      echocardiography, and nuclear thallium scan before treatment and at 6 months. All
      pts showed increased values of WBC and circulating CD34+ following cytokine
      administration. No patient died. All patients completed a 6-months follow-up:
      target lesion revascularization rate was 12,5%, target vessel revascularization
      rate was 37.5%, angiographic mean ejection fraction increased from 49.8+/-11.9 to
      55.4+/-8.7 (p=NS), mean coronary flow reserve from 1.63+/-0.42 to 2.5+/-0.4
      (p=0.001), mean Thallium uptake raised from 55.56+/-16.42% to 67.56+/-13.66%
      (p=0.01), and normally perfused segments from 16% to 52% (p=0.01). CONCLUSION:
      Cytokine-induced BMC mobilization is feasible in AMI pts. Improvements of
      myocardial perfusion can be expected after PTCA associated with G-CSF and GM-CSF
      induced mobilization. Further studies are required to define the role of BMC
      mobilization and the most effective cytokine combination.

PMID- 19755218
TI  - The value of intravascular ultrasound imaging in diagnosis of aortic penetrating
      atherosclerotic ulcer.
AB  - BACKGROUND: Aortic penetrating atherosclerotic ulcer (PAU) is one of the causes
      of acute aortic syndrome. Few studies have evaluated the value of intravascular
      ultrasound (IVUS) imaging in the diagnosis of PAU. OBJECTIVES: We aimed to
      evaluate the value of IVUS imaging in diagnosis of PAU. METHODS AND RESULTS: From
      September 2002 to May 2005, a consecutive series of 15 patients with suspected
      aortic dissection underwent both IVUS imaging and spiral Computed Tomography
      (CT).CT documented 4 PAUs in three patients. There were no complications related
      to IVUS imaging. The common IVUS features of these four PAUs appeared as a
      crescentic, localized, outpouching thickened aortic wall with heterogeneous
      echoic density that communicated with the lumen via a discontinuous intima. By
      using these features, IVUS detected five other PAUs in four patients, which were
      overlooked by CT. The width of PAU detected by CT was significantly wider than
      that of PAU not detected by CT (1.33+/-0.67cm vs 0.43+/-0.27cm, P=0.027). Two of
      five PAUs omitted by initial CT were confirmed by follow-up CT or magnetic
      resonance imaging (MRI). During follow up, three PAUs, including two of those
      overlooked by CT, developed into aneurysms. CONCLUSION: IVUS imaging is a safe
      examination, and more sensitive than spiral CT to diagnose PAU.

PMID- 19755219
TI  - Five month study of percutaneous heart valves in the systemic circulation of
      sheep using a novel model of aortic insufficiency.
AB  - AIMS: To study the 5 month performance of a balloon-expandable percutaneous heart
      valve (PHV) in the systemic circulation of animals. METHODS AND RESULTS: Moderate
      to-severe (>/= grade 3) aortic insufficiency was created in 14 juvenile sheep
      using a bioptome device. A 23mm PHV was implanted distal to the left subclavian
      artery (1.78+/-0.18 cm2 area, 27+/-2 mmHg closing gradient). Valve performance
      was followed angiographically (baseline, 21 weeks) and echocardiographically
      (baseline, 6, 14, 21 weeks). Animals were euthanized at 21 weeks or at the first
      sign of valve dysfunction. Four animals died of acute procedural complications
      (aortic perforation, mitral valve damage, hemothorax, and sheath dissection of
      brachio-cephalic artery). One animal with a rotated PHV (secondary to aortic
      dissection) was euthanized at 6 weeks; 3 animals were euthanized at weeks 6 and
      14 because of decreased leaflet mobility (normal PHV at autopsy, decreased
      mobility related to halothane-induced hypotension). Six animals with normal PHV
      function (1.68+/-0.12 cm2 area, 23+/-4mmHg closing gradient) were euthanized at
      21 weeks; pathologic examination revealed no significant PHV abnormalities.
      Native aortic valve insufficiency was grade 2-4 at 21 weeks. CONCLUSION: PHV
      function remains satisfactory to 21 weeks in the descending aorta. This animal
      model is valid for chronic study of PHV in the systemic circulation.

PMID- 19755220
TI  - Cardiovascular magnetic resonance for the interventionist.
AB  - Cardiovascular magnetic resonance (CMR) continues to provide exceptional quality
      images of cardiac and major vessel anatomy, but recent advances now permit a
      rapid, robust assessment of a diverse spectrum of functional and physiological
      parameters. In the routine CMR investigation of ischaemic heart disease,
      clinicians are now faced with an array of real time on-line rest and stress
      images that encompass cardiac function, perfusion, the presence of infarcted,
      viable and ischaemic myocardium, as well as metabolism. The implementation of
      cardiac dedicated scanners, the ever increasing array of diagnostic information
      available, and the increasing clinical demand for all forms of CMR investigation
      has seen the integration of MRI into cardiology, with cardiologists becoming
      increasingly involved at every stage. With the advent of CMR directed
      intervention and CMR directed therapy, together with the development of combined
      cardiovascular interventional CMR laboratories, interventional cardiologists in
      particular now themselves in the forefront of this pioneering technology.This
      article reviews the key areas of CMR that pertain to the modern interventional
      cardiologist.

PMID- 19755221
TI  - Intracardiac echocardiography during interventional procedures.
AB  - BACKGROUND: As non-surgical percutaneous interventions are increasingly
      considered for many cardiac conditions, high quality near field continuous
      imaging is warranted, in order to optimize the results, and to prevent and detect
      complications. Transesophageal echocardiography is the standard imaging
      technique, however general anesthesia and endotracheal intubation is required
      during prolonged monitoring of percutaneous interventions. Intracardiac
      echocardiography is a novel emerging tool that allows a view within the cardiac
      chambers and the large vessels and can be employed by the interventional
      cardiologist. METHOD: In our department, a phased array, multi-frequency, four
      way steerable catheter (AcuNaV - Siemens) was used for anatomic and haemodynamic
      cardiac assessment and for guidance and monitoring during non-coronary
      percutaneous interventions. In total 135 patients underwent intracardiac
      echocardiographic investigation, 4 during diagnostic heart catheterization, 6
      during percutaneous coronary intervention with the use of a new left ventricular
      assist device, the Impella Recover LP 2.5 system, 26 during percutaneous
      transluminal septal myocardial ablation (10 patients were reevaluated with
      intracardiac echocardiography at 6 months), 50 during interatrial communication
      closure, 4 during percutaneous left atrial appendage transcatheter occlusion, 7
      during percutaneous balloon valvuloplasty, 1 during percutaneous aortic valve
      replacement and 27 during pulmonary vein ablation. All patients tolerated the
      procedure very well with no catheter related complications. However, there were
      two complications, which were due to the guidewire and the sheath, an inferior
      vena cava dissection and a femoral vein dissection, respectively. CONCLUSION:
      Phased array intracardiac imaging is a safe technology, which facilitates non
      surgical interventions by providing high quality images. It eliminates the need
      for general anesthesia and thus increases the patient comfort.

PMID- 19755222
TI  - HELEX Septal Occluder for transcatheter closure of patent foramen ovale:
      multicentre experience.
AB  - AIMS: Patients with cryptogenic embolic events and a patent foramen ovale (PFO)
      are at risk of paradoxical embolism causing recurrent cerebral events; however,
      transcatheter PFO closure remains controversial. The aim of this multicentre
      trial was to demonstrate the feasibility and safety of transcatheter closure of
      PFO with the HELEX Septal Occluder. METHODS AND RESULTS: The study enrolled 128
      patients (66 female; mean age, 50 years). Mean (+/-SD) PFO size was 10+/-3.7 mm;
      38 patients also had an atrial septal aneurysm. Device implantation was
      successful in 127 patients. Device-related events during implantation or follow
      up were device embolisation, wire-frame fracture, and retrieval cord breaks (two
      cases each; no sequelae). Other adverse events included atrial arrhythmia (two
      patients), migraine, convulsion, and transient ischaemic attack (one case each).
      There were no recurrent strokes, deaths, perforations, or accumulations of
      thrombi on the device. Within a mean follow-up period of 21+/-11 months, complete
      PFO closure using one device was achieved in 114 patients (90%). Five patients
      with a moderate to large residual shunt received a second device. CONCLUSION: The
      HELEX Occluder can be used for PFO closure. Device- and procedure-related
      complications are rare. The closure procedure appears to reduce recurrence rates
      of stroke and transient ischaemic attack.

PMID- 19755223
TI  - Percutaneous implantation of the corevalve aortic valve prosthesis for patients
      presenting high risk for surgical valve replacement.

PMID- 19755225
TI  - SR200 MyoCath percutaneous microimplant delivery system.

PMID- 19755224
TI  - Percutaneous aortic valve replacement in a patient who could not undergo surgical
      treatment. A case report with the CoreValve aortic valve prosthesis.

PMID- 19755226
TI  - Reliable angiographic evaluation by 64-slice computed tomography after
      trifurcation stenting of the left main coronary artery.

PMID- 19755227
TI  - Paclitaxel-eluting stent restenosis shows three-layer appearance by optical
      coherence tomography.

PMID- 19755228
TI  - Editorial.

PMID- 19755229
TI  - Drug Eluting Stents: promises and the precautionary attitude(Gruentzig lecture at
      the ESC Stockholm, 2005).

PMID- 19755230
TI  - Physicians, the medical device industry and the data; a healthy relationship?

PMID- 19755231
TI  - Drug-eluting stent implantation in acute myocardial infarction. Do we need
      another randomised trial? (TYPHOON, PASSION and HORIZONS trials).

PMID- 19755232
TI  - Left ventricular assist devices in cardiogenic shock and high-risk PCI.

PMID- 19755234
TI  - Pioneer clinical experiences: from bare metal Palmaz-Schatzto Sirolimus-Eluting
      CYPHER stents.

PMID- 19755233
TI  - Curriculum and syllabus for Interventional Cardiology subspecialty training in
      Europe.

PMID- 19755235
TI  - Coronary stenting: the first 10 years.

PMID- 19755236
TI  - Direct stenting of de novo coronary stenoses with tacrolimus-eluting versus
      carbon-coated carbostents. The randomized JUPITER II trial.
AB  - AIMS: Drug-eluting stents are being increasingly used for the treatment of de
      novo coronary lesions. This trial compared the performance of tacrolimus-eluting
      stents (TES) with that of equivalent carbon-coated stents (CCS). METHODS AND
      RESULTS: The JUPITER II trial enrolled 332 patients (mean age = 64 years, 75%
      men) with de novo coronary stenoses. Patients were randomly assigned to TES
      versus CCS and underwent repeat coronary angiography at 6 months. The primary
      study endpoint was in-stent and in-segment late lumen loss (LLL). The main
      secondary endpoints included binary restenosis, and rates of major adverse
      clinical events (MACE), including death, myocardial infarction, target lesion
      revascularisation and stent thrombosis at 1, 6, and 12 months of follow-up. The
      procedure was successful in 99.4% of patients in both groups. There was no
      procedural death, 1 cardiac death at 2 months, and 1 acute and 2 subacute CCS
      thromboses. Angiographic follow-ups were available in 94.4% and 95.1% of patients
      assigned to TES and CCS, respectively. The mean in-segment and in-stent LLL was
      0.42+/-0.46 mm and 0.65+/-0.47 mm, respectively, in the TES, versus 0.48+/-0.52
      mm and 0.66+/-0.53 mm, respectively, in the CCS group (ns). The 12-month
      cumulative MACE rate was 19.5% in the CCS versus 16.1% in the TES group (ns).
      CONCLUSIONS: Both stents showed high safety, with no stent thrombosis in the TES
      group. No difference was observed in 6-month angiographic results and 12-month
      MACE rates between TES and CCS.

PMID- 19755237
TI  - Revascularization strategies of coronary multiple vessel disease in the Drug
      Eluting Stent Era: one year follow-up results of the ERACI III Trial.
AB  - OBJECTIVE: To compare the incidence of major adverse cardiac and cerebrovascular
      events (MACCE) in patients with multiple vessel coronary artery disease treated
      with drug eluted stents (DES), bare metal stents, percutaneous coronary
      interventions (PCI) or bypass surgery (CABG). METHODS: In the Argentine
      Randomized Study Coronary Angioplasty versus Coronary Bypass Surgery in Multiple
      Vessel Disease (ERACI) III trial, 225 patients with multivessel disease who
      received DES met clinical and angiographic inclusion criteria for the ERACI II
      trial. This cohort (ERACI III-DES) was compared to both ERACI II treatment arms
      (ERACII-PCI and ERACI II-CABG). The primary end point was freedom from MACCE at
      one year. RESULTS: Comparison of baseline demographic and angiographic data,
      revealed that ERACI III-DES patients were older, smoked more, had more diabetes,
      hyperlipidaemia, hypertension, type C lesions and received more stents. At one
      year freedom from MACCE was significantly greater in ERACI III-DES cohort (88%)
      than ERACI II CABG (80.5% p=0.038) and ERACI II PCI (78% p=0.006) patients. The
      ERACI III-DES cohort had similar freedom from death and acute myocardial
      infarction (AMI) to ERACI II PCI patients but greater than ERACI II-CABG arm.
      Freedom from repeat revascularization was similar between ERACI III-DES to ERACI
      II-CABG (95.1% p=ns) patients, but both were significantly better than those in
      the ERACI II-PCI arm ( 91.2% and 83%p=0.002 and 0.02 respectively). CONCLUSION:
      Patients with multiple vessel disease treated with DES in ERACI III had better
      one year outcomes than those treated with PCI or CABG in ERACI II.

PMID- 19755238
TI  - Integrated analysis of medically treated diabetic patients in the TAXUS(R)
      program: benefits across stent platforms, paclitaxel release formulations, and
      diabetic treatments.
AB  - OBJECTIVES: The TAXUS(R) database was used to perform an integrated analysis
      across several large phase II and III trials to assess outcomes of polymer-based
      paclitaxel-eluting TAXUS stents in diabetic patients. BACKGROUND: While drug
      eluting stents have reduced the risk for restenosis, diabetic patients remain at
      higher risk. METHODS: This post hoc analysis of clinical and angiographic
      outcomes combined individual patient data from four randomized, multicentre,
      controlled clinical trials (TAXUS II, IV, V, and VI) representing outcomes across
      two paclitaxel release formulations and stent platforms. RESULTS: Breslow-Day
      analysis indicated homogeneous odds ratios across dose formulations and stent
      platforms, thus clinical data (9 months) were pooled from 3445 patients,
      including 814 diabetic patients. The randomized quantitative coronary angiography
      subset (n=2863) included 469 diabetic patients requiring oral medications only
      and 216 insulin-treated. Among patients receiving bare metal stents (BMS), those
      with diabetes had worse clinical and angiographic outcomes than non-diabetic
      patients. Target lesion revascularization rates were decreased in TAXUS patients
      relative to BMS controls by 59% (p=0.0001) among diabetic patients requiring oral
      medications, by 66% (p=0.006) among insulin-treated. Insulin-treated patients
      showed a significant TAXUS benefit for in-stent and in-segment percent diameter
      stenosis (p=0.0001, p=0.001, respectively) and late loss (p=0.001); a similar
      TAXUS benefit was seen in diabetic patients treated with oral medications
      (p<0.0001). Binary restenosis in-segment was significantly decreased 65% in both
      diabetic subsets (p=0.0001). CONCLUSION: This post hoc analysis of data from four
      combined randomized TAXUS trials suggests the TAXUS benefit observed in non
      diabetic patients is carried over into the high-risk diabetic population.

PMID- 19755239
TI  - One-year results of coronary revascularization in diabetic patients with
      multivessel coronary artery disease.Sirolimus stent vs. coronary artery bypass
      surgery and bare metal stent: insights from ARTS-II and ARTS-I.
AB  - BACKGROUND: ARTS-II was designed to evaluate the sirolimus-eluting stent (SES)
      versus ARTS-I. The objective of this analysis is to assess the safety and
      efficacy of the SES in diabetic patients with multivessel disease (MVD) versus
      both arms of ARTS-I. METHODS AND RESULTS: The ARTS studies included 367 diabetic
      patients (ARTS-II: 159; ARTS-I-CABG: 96; ARTS-I-PCI: 112). Baseline
      characteristics showed a more diseased patient population in the ARTS-II study:
      50.3% with 3VD vs. 35.4% (ARTS-I-CABG) and 30.8% (ARTS-I-PCI) (p=0.003). Treated
      or anastomosed lesions were 3.2+/-1.2 (ARTS-II), 2.8+/-0.8 (ARTS-I-CABG) and
      2.5+/-1.1 (ARTS-I-PCI). At 30 days there was a significant difference in MACCE
      between ARTS-II (4.4%) and ARTS-I-PCI (12.5%) (p=0.02). At 1-year, the death rate
      was 2.5% (ARTS-II) vs. 3.1% (ARTS-I-CABG) and 6.3% (ARTS-I-PCI) without
      significant differences. Myocardial infarction rate was 0.6% (ARTS-II) vs. 2.1%
      (ARTS-I-CABG; p=0.56) and 6.3% (ARTS-I-PCI; p=0.01). The need for repeat
      revascularization was 12.6% (ARTS-II) vs. 4.2% (ARTS-I-CABG; p=0.027) and 22.3%
      (ARTS-I-PCI; p= 0.046). MACCE-free survival was 84.3% (ARTS-II) vs. 85.4% (ARTS-I
      CABG; p=0.86) and 63.4% (ARTS-I-PCI; p<0.001). Also at 1 year, the overall MACCE
      rate in patients with diabetes was significantly higher than in nondiabetic
      patients, 15.7% vs. 8.5%, respectively [RR 1.85, 95%CI (1.16,2.97), p=0.015), due
      to a higher incidence of death and need for repeat revascularization, 2.5% vs.
      0.4 and 12.5% vs. 5.6% in diabetes vs. nondiabetes groups, respectively.
      CONCLUSION: Despite more extensive and treated disease, the overall MACCE-free
      survival in diabetic patients at 1 year in ARTS-II is similar to ARTS-I-CABG.

PMID- 19755240
TI  - First-In-Man application of a miniature self-contained intracoronary magnetic
      resonance probe. A multi-centre safety and feasibility trial.
AB  - AIMS: To assess safety and feasibility of intracoronary Magnetic Resonance (MR)
      Spectroscopy in living patients, using a self-contained MR catheter. METHODS AND
      RESULTS: Prospective, multi-centre study in patients with stable or unstable
      angina that were scheduled for percutaneous coronary diagnostic or therapeutic
      catheterization. We assessed the feasibility of an intravascular MR catheter,
      capable of analysing the arterial wall without external magnets or coils, by
      differentiating lipid rich, intermediate and fibrotic areas of the
      atherosclerotic plaque on the basis of differential water diffusion.Twenty-nine
      patients were included at 4 centres. The intracoronary MR-spectroscopy procedure
      was well tolerated; no MACE and no device related serious adverse event was
      observed. The MR catheter was successfully advanced into the lesion in 28
      patients. Introduction of the MR catheter was not possible in one patient with a
      tortuous proximal right coronary artery. MR data were obtained in 22 patients.
      According to the predominant MR pattern, lesions were classified as fibrous
      plaque in 4 patients, as intermediate plaque in 4 patients and as lipid-rich
      plaque in 8 patients. Six patients were excluded from analysis because artifacts
      impeded the quality of the MR signal. Plaque type did not show a correlation with
      angina status (p=0.552; all groups) or angiographic parameters, such as minimal
      lumen diameter and diameter stenosis. CONCLUSIONS: This prospective, multi-centre
      study demonstrates for the first time that coronary artery assessment of
      potentially vulnerable, non-flow limiting lesions using a dedicated intravascular
      MR catheter, free of external magnets or coils, is feasible in clinical practice.
      Assessment of the coronary wall may provide important data regarding the
      composition of the atherosclerotic lesion, which then could contribute to
      predicting the likelihood of eventual rupture and clinical instability.

PMID- 19755241
TI  - First experience with the Impella Recover(R) LP 2.5 micro axial pump in patients
      with cardiogenic shock or undergoing high-risk revascularisation.
AB  - AIM: To study the feasibility, safety and efficacy of the Recover(R) LP 2.5
      assist device in patients scheduled for high risk off-pump coronary bypass
      surgery, percutaneous coronary intervention or patients in cardiogenic shock.
      METHODS AND RESULTS: 40 patients presenting with cardiogenic shock (n=13) or
      scheduled for a high risk revascularisation (n=27) were included.36 were selected
      for safety and feasibility analysis. In 3 patients the pump could not be placed
      in an adequate position. 5 patients had access related complications. In 9
      patients free Hb rose above 80 mg/dl. 3 malfunctions and early device-removal
      occurred. After device modifications these problems did not recur. CO in the
      shock group increased significantly: 4.4 l/min+/-1.9 to 4.8 l/min+/-1.2
      (p=0.0178).The left ventricular filling pressures decreased in both groups (22
      mmHg+/-7.5 to 16 mmHg+/-6 in the shock group, [p=0.0008] and over 6 hours from
      14.3 mmHg+/-5.8 to 10 mmHg+/-2.9 in the high-risk revascularisation
      group,[p=0.0327]). CONCLUSIONS: The Recover(R) LP 2.5 micro axial pump allows,
      via percutaneous approach, partial unloading of the left ventricle. The technique
      is, after design modifications, feasible and safe and results in haemodynamic
      improvement.

PMID- 19755242
TI  - Use of Impella Recover(R) LP 2.5 left ventricular assist device during high-risk
      percutaneous coronary interventions; clinical, haemodynamic and biochemical
      findings.
AB  - AIM: To investigate in terms of clinical, haemodynamic and biochemical profile
      the safety and efficacy of the Impella Recover(R) LP 2.5 left ventricular assist
      device during elective high risk percutaneous coronary interventions (HR-PCI).
      METHODS AND RESULTS: Ten out of twelve patients were initially enrolled to
      receive PCI supported by the Impella catheter; eight underwent pressure-volume
      (PV) loop analysis while one patient was monitored by intra-cardiac
      echocardiographic. Free haemoglobin (fHb), B-type natriuretic pepetide,
      catecholamines, aldosterone, angiotensin II, and endothelin were assessed before,
      every 40 minutes as average during the procedure and at 3, 12, 24 and 48 hours
      after intervention. The Impella catheter was used for 144+/-88 min [median (IQR)
      108 (85-198)], and was removed immediately after the procedure in all but one
      patients. In 6, 3 and 2 patients, fHb levels increased above 1, 5 and 10 times
      the upper limit of normal (ULN), respectively. No significant effect was found on
      the tested biomarkers in Impella-supported procedures. The PV analysis showed the
      occurrence of an acute volume increase in the majority of patients immediately
      after Impella insertion that tended to persist even at maximal pump speed. This
      was confirmed by the intracardiac echocardiography that was performed in one
      patient. CONCLUSIONS: Our data, although preliminary due to the limited sample
      size, does not encourage the routine use of Impella Recover(R) LP 2.5 in HR-PCI.
      Additional studies are required to confirm and elucidate the mechanisms
      responsible for the acute LV volume loading and to quantify the degree of
      haemolysis induced by the pump in a broader set of patients.

PMID- 19755243
TI  - Development and construct validation of performance metrics for multivessel
      coronary interventions on the VIST virtual reality simulator at PCR2005.
AB  - BACKGROUND: The first aim of this study was the development of performance
      metrics in a virtual reality simulation for interventional procedure in a real
      case of multivessel coronary disease. A second aim was to assess the construct
      validity of these metrics by comparing the performance of interventional
      cardiologists with different levels of experience. METHODS: Ninety-four
      practicing interventional cardiologists attending the EuroPCR 2005 in Paris,
      France participated in this study. Complete data was available on eighty-nine
      participants (95%). Participants were divided into three categories depending on
      experience. Group 1 (novices): N = 33, < 1 years experience; Group 2
      (intermediate experience): N = 14, >50 cases per year for the last two years and
      Group 3 (master physicians): N = 42 participants completed > 100 cases per year
      during the last five years. PROCEDURE: Over a period of months during 2004-2005
      we identified potential performance metrics for cases of coronary artery disease
      which were then applied to a case of a patient admitted because of stable angina
      (class 1) with multivessel coronary disease. Patient's coronary anatomy and
      lesions were then reconstructed and implemented for the VIST virtual reality
      simulator. All participants were required to perform this case. RESULTS: Overall,
      experienced interventional cardiologists performed significantly better than the
      novices for traditional metrics such as time (p = 0.03), contrast fluid (p =
      0.0008) and Fluroscopy time (p = 0.005). Master physicians performed
      significantly better than the other two groups on metrics which assessed
      technical performance e.g., time to ascend the aorta (p = 0.0004) and stent
      placement accuracy (p = 0.02). Furthermore, master physicians made fewer handling
      errors than the intermediated group who in turn made fewer than the novice group
      (p = 0.0003). Performance consistency was also a linear function of experience.
      CONCLUSIONS: Novel performance metrics developed for the assessment of technical
      skills for a simulated intervention for multi-vessel coronary disease showed that
      more experienced interventional cardiologists performed the procedure better than
      less experienced interventionalists thus demonstrating construct validity of the
      metrics.

PMID- 19755244
TI  - Percutaneous treatment of ischaemic mitral regurgitation in sheep.
AB  - AIMS: A percutaneous mitral annuloplasty device for implantation in the coronary
      sinus was evaluated in surviving sheep with ischaemia-induced mitral
      regurgitation. METHODS AND RESULTS: Microspheres were injected in the left
      coronary artery of thirty-seven sheep. The treatment was repeated in one month
      intervals until the resulting myocardial infarctions caused significant mitral
      regurgitation. Fourteen animals developed a mitral regurgitation degree 2 or
      higher after 130+/-16 days and 3.4+/-0.4 treatments. The annuloplasty device was
      implanted percutaneously within the coronary sinus and the animals were followed
      97+/-6 days (n=14) with monthly intracardiac echocardiograms. The MR grade (0-4)
      decreased from 3.1+/-0.2 at the time for implantation to 0.8+/-0.2 (p=0.0005) at
      the 3 month follow up. The vena contracta decreased from 6.5+/-0.4 mm to 2.0+/
      0.7 mm after 3 months (p=0.0007). The mitral septo-lateral diameter was reduced
      after insertion of the device, from 38+/-1 mm before implantation to 35+/-1 mm
      after 3 months (P=0.0322). Angiography showed no signs of impairment of the
      coronary arteries. No thrombosis was observed. CONCLUSION: These results indicate
      that experimentally induced ischaemic mitral regurgitation can be significantly
      reduced by means of a percutaneous catheter technique from the coronary sinus in
      surviving sheep.

PMID- 19755245
TI  - Hydroxyapatite-coated cardiovascular stents.

PMID- 19755246
TI  - The Recover(R) LP 2.5 catheter-mounted left ventricular assist device.

PMID- 19755247
TI  - AngioJet(R) Rheolytic Thrombectomy System and Innovation for Power Pulse
      Infusion.

PMID- 19755248
TI  - Left ventricular apex occluder. Description of a Ventricular Partitioning Device.

PMID- 19755249
TI  - Percutaneous ventricular restoration in a chronic heart failure patient.

PMID- 19755250
TI  - IVUS beyond the horizon.

PMID- 19755251
TI  - The future: EuroPCR and the European Association of Percutaneous Cardiovascular
      Interventions (EAPCI).

PMID- 19755252
TI  - Stent coating with titanium-nitride-oxide for prevention of restenosis.

PMID- 19755253
TI  - Percutaneous coronary intervention for bifurcation disease.A consensus view from
      the first meeting of the European Bifurcation Club.

PMID- 19755254
TI  - The inoperable valvular heart disease patient:the pluses and minuses of
      percutaneous valvular replacement.
AB  - The spectrum of potentially successful treatment options for inoperable valvular
      disease is limited. Aortic valvuloplasty may offer temporary improvement in
      symptoms and some survival benefit in select non-surgical patients with aortic
      stenosis, but it does not improve long-term outcome. Mitral valve incompetence
      often responds well to surgical repair, though patients with significantly
      reduced left ventricular function have worsened outcomes. The design of a
      percutaneous implantable prosthetic heart valve is a promising alternative to
      valvuloplasty. Although not yet an established interventional method,
      Percutaneous Aortic Valve Replacement (PAVR) will likely take a position among
      the innovative catheter-based techniques currently in development. The
      appropriate clinical scenario for Percutaneous Mitral Valve Intervention (PMVI),
      however, may be significantly narrower. As with many other minimally invasive
      operations or procedures, the ethical considerations of a novel approach must be
      considered.

PMID- 19755255
TI  - Comparison of the CardioShield filter with the guardwire balloon in the
      prevention of embolisation during vein graft intervention: results from the
      CAPTIVE randomised trial.
AB  - AIMS: This study assessed safety and efficacy of a third-generation distal
      protection device, MedNova CardioShield Bare Wire Myocardial Protection System,
      for treating Saphenous Vein Graft (SVG) disease.Treatment of SVG disease remains
      difficult, with increased adverse cardiac events (MACE) primarily manifested as
      no reflow and periprocedural infarction. Even with approved embolic protection
      devices, 30-day MACE rates are approximately 10%. METHODS AND RESULTS: A
      multicentre randomized clinical trial evaluated a third-generation distal
      protection device MedNova CardioShield vs Percusurge GuardWire in 652 patients
      undergoing treatment of SVG disease, using a primary endpoint of 30-day death, Q
      wave, non-Q-wave infarction, or target vessel revascularisation (MACE).The
      primary endpoint occurred in 11.4% with CardioShield vs 9.1% with GuardWire
      (P=.37). Intention-to-treat analysis showed a strong trend for noninferiority
      (P=.057). Secondary modified intention-to-treat analysis including only patients
      receiving treatment device and no protocol deviation (defined as treatment of
      another lesion not using embolic protection) supported noninferiority of
      CardioShield (P=.022). CONCLUSION: Analysis of outcomes of treatment strategies
      for SVG disease is difficult. In this trial, final results depended on whether a
      patient actually received the device according to protocol. With 30-day MACE as
      primary endpoint, CardioShield was not demonstrated to be noninferior to
      GuardWire.

PMID- 19755256
TI  - Comparison of sirolimus-eluting vs. bare-metal stents for the treatment of
      infrapopliteal obstructions.
AB  - BACKGROUND: Drug-eluting stents have been shown to be very effective in the
      treatment of coronary artery disease. In this independent, single-centre registry
      we assess the safety and efficacy of the sirolimus-eluting stent versus bare
      metal balloon expandable stent for symptomatic infrapopliteal obstructions.
      METHODS AND RESULTS: A total of 60 consecutive patients with infrapopliteal
      arterial obstructions were treated by stent implantation into the tibial and
      peroneal arteries and the data was entered into a prospective registry. All
      patients were treated with balloon-expandable coronary stents with a stent length
      of 33 mm and a nominal diameter of 3.5 mm. Enrolment was limited to patients
      treatable with a single stent. 30 patients (56.7% male, mean age 71.4 years,
      83.3% diabetics) received a sirolimus-eluting balloon-expandable stent. 30
      patients (63.3% male, mean age 73.0 years, 76.6% diabetics) were treated with
      uncoated bare-metal stents. At follow-up, the cumulative rates of Major Adverse
      Events were 10.0% vs. 46.6%. The rates of major amputation, bypass surgery or
      Target Lesion Revascularisation (TLR) were all zero for the sirolimus group
      compared with 10.0%, 0% and 23.3% in the bare metal stent group. There were 7
      deaths (sirolimus =3, bare metal =7). Angiographic follow-up comparing sirolimus
      vs. bare metal revealed stent occlusion 0% vs. 17.4%, restenosis >50% of 0% vs.
      39.1% (p 0.0007) and mean degree of in-stent restenosis of 1.8+/-4.8% vs. 53+/
      40.9% (p <0.0001) respectively. CONCLUSION: In this registry sirolimus-eluting
      stents were shown to be safe and effective in the treatment of focal
      infrapopliteal obstructions.

PMID- 19755257
TI  - Sex differences and their impact on clinical outcome after percutaneous or
      surgical revascularisation: a report from the Arterial Revascularisation
      Therapies Study (ARTS).
AB  - AIMS: To determine whether women have an unfavorable outcome after coronary
      interventions compared with men, we evaluated patients undergoing
      revascularisation within the Arterial Revascularisation Therapies Study (ARTS).
      METHODS AND RESULTS: We evaluated 1205 patients (23% women) with multivessel
      disease randomised to percutaneous or surgical coronary revascularisation. The in
      hospital results, and clinical outcome at five years were evaluated. Women were
      older, with a higher prevalence of hypertension, hypercholesterolaemia, family
      history for coronary artery disease (all p<0.001), diabetes mellitus (p=0.05) and
      stable angina (p<0.05) than men, but had a lower incidence of history of
      myocardial infarction or smoking (both p<0.001). More major bleeding
      complications, even after adjusting for baseline clinical characteristics (OR
      29.4, 95% CI: 5.3-500, p<0.005) were observed in women following percutaneous
      coronary intervention. During clinical follow-up freedom from major adverse
      cardiac and cerebrovascular events was similar in men and women, regardless of
      treatment strategy. Men assigned to bypass surgery had a better quality of life,
      but women reported more frequently angina. CONCLUSION: The clinical outcome of
      women with multivessel disease undergoing coronary revascularisation was similar
      to that in men. However, women presented more bleeding complications before
      hospital discharge, and had less favourable assessment in specific domain of
      daily life at follow-up.

PMID- 19755258
TI  - Surgical isolated edge-to-edge mitral valve repair without annuloplasty: clinical
      proof of the principle for an endovascular approach.
AB  - AIMS: A variety of endovascular technologies for valve repair for mitral
      regurgitation (MR) are under development. Endovascular Edge-to-Edge (E2E)
      approach recently entered the clinical trial phase. The aim of the present study
      was to determine the effectiveness of surgical isolated E2E repair without
      annuloplasty to predict the efficacy of the endovascular E2E approach. METHODS
      AND RESULTS: Clinical and echocardiographic data of 29 patients with either
      degenerative or functional MR who had surgical E2E repair without annuloplasty,
      were retrospectively analysed. Mean age was 63.8+/-8.79 years, 45% were in NYHA
      class III or IV and 41% had a left ventricular ejection fraction less than 60%.
      Hospital mortality was 3.4% and overall survival after a mean follow-up of 6.8
      year was 93%. At latest follow-up, 68% of patients were in NYHA class I, 28% in
      class II and 4% in class III; 86% of patients had MR < grade 2. Two patients with
      recurrent grade 4 MR underwent re-operation. The 5 years freedom from the
      combined end-point of recurrent MR>2+ and re-operation, was 90+/-5%. CONCLUSIONS:
      Isolated surgical E2E mitral repair, intentionally performed without
      annuloplasty, has acceptable midterm results for degenerative and functional MR,
      comparable to conventional repair techniques with annuloplasty. These results
      encourage the evaluation of less invasive endovascular E2E repair approaches in a
      clinical setting.

PMID- 19755259
TI  - Real world experience with the TITAN(R) stent: a 9-month follow-up report from
      The Titan PORI Registry.
AB  - AIMS: The aim of the Titan PORI Registry was to evaluate the safety and efficacy
      of a stainless steel stent coated with titanium nitride oxide (Titan(R),
      Hexacath, France) in routine clinical practice. METHODS AND RESULTS: We report a
      prospective single-centre experience in treating patients with the Titan(R)
      stent. All consecutive patients receiving Titan(R) stent(s) were enrolled. The
      choice of a stent was at the discretion of the operator with no exclusion
      criteria. The primary end point of the registry was Major Adverse Cardiac Events
      (MACE) at 6 and 9 months. A total of 210 lesions were treated in 193 enrolled
      patients (mean age 67+/-10; men 71%; diabetes 17%). Lesions were of type B in 64%
      and type C in 23%. The indications for PCI were unstable angina or non-Q-wave MI
      in 36% and acute STEMI in 30% of the patients. Mean reference diameter was 2.9+/
      0.3 mm and mean lesion length 12.9+/-3.0 mm. Mean stent size was 2.98 mm (range 2
      3.5 mm) and length 15.5 mm (range 7-28 mm). Stent delivery was successful in all
      cases (23% direct stenting). Complete follow-up of all 193 patients was obtained
      up to 9 months. There were no in-hospital or 30-day MACE observed. At 270 days,
      the MACE rate was 10.4% (MI 4.1%, cardiac death 0%, TVR 8.3%). There were no
      cases with stent thrombosis. CONCLUSION: These medium term data confirm good
      safety profile of Titan(R) stent even in high risk patients and complex coronary
      lesions in routine clinical use.

PMID- 19755260
TI  - The Titanium-NO Stent:results of a multicenter registry.
AB  - BACKGROUND: Contemporary stents discharge nickel, chromium and molybdenum which
      might contribute to restenosis. The Titan stent is coated with titanium nitride
      oxide that prevents completely discharge of metal elements. AIMS: To assess short
      and long term outcome of the Titan in a multi-centre registry. METHODS: Included
      were all patients except those in cardiogenic shock. Titan stents were 2.0-5.0 mm
      in diameter and 7-28 mm in length. Clinical follow-up was performed at 30 days
      and 6 months. RESULTS: Total of 333 Titan stents were implanted in 296 patients
      (age 68.8+/-11.8 years, 81% men). Risk factors included hypercholesterolaemia
      (61.3%), hypertension (51.3%), diabetes mellitus (DM) (36.6%) and current smoking
      (27.6%). Eighty-one percent of patients had Acute Coronary Syndrome (ACS). Sixty
      two percent of treated lesions were B2/C type. Lesion length was 17.5+/-14.8 mm
      and stent diameter was 3.0+/-2.12 mm.Procedural success was 99.7%. At 180 days,
      6.3% of patients had a total of 7.6% MACE including 5.4% TLR, 0.7% MI, 0.7% stent
      thrombosis and 0.7% death. CONCLUSION: The Titan stent has a remarkable safety
      profile. Notwithstanding the highly complicated lesion and case mix, the short-
      and long-term results of this registry approach those of drug-eluting stents.

PMID- 19755261
TI  - Iatrogenic dissection of the ascending aorta following heart catheterisation:
      incidence, management and outcome.
AB  - AIMS: Iatrogenic ascending aorta dissection (AAD) is an uncommon complication
      following heart catheterisation. AIMS of this study were to determine the
      incidence, to identify the predisposing procedural factors and to define the
      management and the outcomes of patients suffering from iatrogenic AD. METHODS AND
      RESULTS: Between January 1996 and May 2005, iatrogenic AAD that occurred during
      cardiac catheterisations, were retrospectively identified from clinical and peri
      procedural data prospectively collected in a dedicated database. At least 1-month
      clinical follow-up (median 25 months; range 5-77) was obtained in all patients
      complicated with iatrogenic AD. The overall incidence of iatrogenic AAD was
      0.04%; this incidence was significantly higher after interventional procedures
      (0.12%) than after diagnostic procedures (0.01%; p=0.0001). Most of dissections
      were located in the right coronary sinus (12 patients; 67%) and limited to the
      corresponding coronary sinus (Dunning class I: 11 patients; 61%). Manoeuvres most
      often involved were coronary engagement with the use of non-conventional
      catheters. Conservative treatment with sealing the entry door by a stent 10
      patients (56%) or expectant management 7 patients (39%) resulted in favourable
      outcomes as none of patients died during hospitalisation and follow-up.
      CONCLUSIONS: Iatrogenic AAD is a rare complication following cardiac
      catheterisation that in the vast majority of patients may benefit from
      conservative treatment with good long-term outcomes.

PMID- 19755262
TI  - N-terminal pro-brain natriuretic peptide level in relation to epicardial and
      myocardial reperfusion in ST-segment elevation myocardial infarction treated with
      facilitated angioplasty.
AB  - The aims of this study were firstly to evaluate the relations between N-terminal
      pro-brain natriuretic peptide (NT-proBNP) concentration after ST-segment
      elevation myocardial infarction (STEMI) and reperfusion injury, and secondly to
      assess the prognostic value of NT-proBNP. METHODS AND RESULTS: We evaluated 202
      consecutive patients with STEMI treated with facilitated angioplasty (PCI). TIMI
      flow, TIMI myocardial perfusion grade (TMPG) and ST-segment elevation resolution
      (iST) were assessed before O and 30 minutes (O30) after PCI. Enzymatic injury was
      expressed as an area under the curve of CK-MB release (AUC, [Uxh]). 48 hours
      after PCI, the concentration of NT-proBNP ([pg/ml]) and echocardiography
      determined left ventricle ejection fraction (LVEF, [%]) were assessed. Death and
      heart failure (HF) requiring hospitalisation were recorded during a 1-year follow
      up and defined as a composite endpoint. NT-proBNP concentration 48 hours after
      PCI was correlated with iST-O (p<0,001; r=0,48), iST-O30 (p<0,001; r=0,57), AUC
      (p<0,001; r=0,54) and LVEF (p<0,001; r=-0,5). Increasing quartiles of NT-proBNP
      were related to mortality (p=0,0012) as well as to composite endpoint (p=0,0012)
      at 1 year. 4th-quartile of NT-proBNP was independently associated with a
      composite endpoint at a 1-year follow-up. CONCLUSIONS: NT-proBNP level after
      STEMI was moderately correlated with the degree of microvascular reperfusion and
      myocardial injury and function. NT-proBNP was independently associated with the
      frequency of death and HF requiring hospitalisation.

PMID- 19755263
TI  - Intracoronary nicorandil prior to reperfusion in acute myocardial infarction.
AB  - BACKGROUND: A prospective, randomised, single centre study was designed to test
      the safety and efficacy of nicorandil infusion, a potassium channel opener, prior
      to reperfusion in ST-elevation acute myocardial infarction (STEMI). METHODS AND
      RESULTS: Seventy STEMI patients with TIMI 0 to 2 flow were randomly assigned to
      nicorandil (Group N; n = 35) or control (Group C; n = 35) and underwent direct
      percutaneous coronary intervention (PCI). In Group N, 2 mg of nicorandil was
      infused directly into the infarct area prior to reperfusion. Incidence of
      anterior infarction was 60% in both groups. With nicorandil infusion, additional
      ST elevations without chest pain were observed for a few minutes in 94% of cases.
      However, no ventricular fibrillation or ventricular tachycardia occurred. TIMI
      myocardial perfusion grade 3 was significantly higher in Group N (40% vs. 17%,
      p<0.01). Patients were followed for up to 8 months, with similar incidence of
      major clinical adverse events, however left ventricular regional wall motion
      score significantly improved in Group N (P < 0.05). The effect of nicorandil was
      seen in patients without ischaemic preconditioning (P < 0.05). CONCLUSION: This
      study suggests that direct infusion of nicorandil prior to revascularisation may
      be safe and beneficial.

PMID- 19755264
TI  - Clinical and angiographic follow-up after overlapping implantation of
      polytetrafluoroethylene covered stents with drug eluting stents.
AB  - Polytetrafluoroethylene-covered stents (PCS) were recently proposed as a new
      modality mainly for the treatment of saphenous vein graft lesions, but restenosis
      occurring principally at the edges restricted their clinical use in the
      management of coronary aneurysms and perforations. AIMS: To investigate the
      safety and effectiveness of the overlapping implantation of drug-eluting stents
      (DES) with PCS in clinical scenarios where the latter are indicated. METHODS:
      Since April 2002, when DES were introduced in clinical practice, 14 consecutive
      patients were -treated with overlapping implantation of PCS with DES in 3
      centres. Seven patients were treated for coronary aneurysms, 5 for coronary
      perforations and 2 for branch occlusion. The incidence of any major adverse
      cardiac events defined as death, myocardial infarction (MI), and target vessel
      revascularisation (TVR) was retrospectively evaluated. A control angiography was
      available in 13 patients, and quantitative coronary angiography was performed
      before and after the intervention and at follow-up to evaluate restenosis rate
      and late loss. RESULTS: At a mean clinical follow-up of 21.9 months there were no
      deaths or MI's, while one patient with occlusive restenosis underwent successful
      TVR (7.7%). At angiographic follow-up (mean: 9.7 months) there was one patient
      with restenosis (7.7%), who had a total occlusion. After excluding the patient
      with the occlusive restenosis mean diameter stenosis was 22.4+/-11.7% and late
      loss was 0.18+/-0.35 mm at follow-up. No early or late stent thrombosis occurred.
      CONCLUSION: Overlapping implantation of PCS with DES seems to be a safe and
      effective therapeutic modality demonstrating a low incidence of clinical and
      angiographic restenosis.

PMID- 19755265
TI  - Myocardial perfusion scintigraphy to predict outcomes after coronary stenting.
AB  - The value of myocardial perfusion scintigraphy (MPS) in predicting the occurrence
      of restenosis or new coronary lesions after stent implantation is debatable. A
      total of 47 patients treated with successful bare stent implantation underwent
      stress gated SPECT MPS at three time-points: pre-procedure, early pos-procedure,
      and 6-month follow-up. Follow-up angiographic re-study was obtained at 6 months.
      Overall, 51.1% of patients had angiographic in-stent restenosis or a new lesion
      at follow-up. Pre-procedure MPS and early MPS scans did not differ between
      patients with or without restenosis/new lesions. At follow-up transient perfusion
      defects were observed in 26.1% of patients without restenosis/new lesions and in
      75.0% of patients presenting with restenosis/new lesions (p<0.01) (sensitivity:
      75.0%; especificity: 73.9%). When comparing early post procedure MPS to follow-up
      MPS, patients without restenosis/new lesions had no changes or a decrease in the
      number of segments with transient defects (median difference 0 [interquartile
      range -2 - 0]), while patients with restenosis/new lesions had an increase in
      transient defects (+2 [interquartile range 2 - 3.75]; p<0.01). Two multivariate
      factors independently predicted new lesion/restenosis: reference diameter < 2.9
      mm (OR 6.50; p=0.05) and the difference in the number of segments with transient
      defects between early post procedure and follow-up MPS (OR 1.87; p<0.01). In
      conclusion, pre-procedure and early MPS did not predict complications after
      coronary stenting, while follow-up MPS was suboptimal in differentiating patients
      with or without new lesions/restenosis. However, the change in myocardial
      perfusion from early post-procedure to the follow-up scan was an important 
      prognostic factor to predict the incidence of new lesion/restenosis.

PMID- 19755266
TI  - Low incidence of cardiac biomarker elevation following PCI of chronic total
      coronary occlusions.
AB  - BACKGROUND AND OBJECTIVES: After a percutaneous coronary intervention (PCI)
      creatine kinase-MB fraction (CK-MB) elevation is observed in 5 to 30% of the
      cases. The often long and diffuse lesions of chronic total coronary occlusions
      (CTO) could represent a high risk group. However, there is no systematic data
      available on the incidence of elevation of cardiac troponin I (cTNI) after
      recanalisation of CTOs. METHODS: In 201 patients a CTO was successfully
      recanalised with stenting of all lesions and the regional wall motion (WMSI) was
      assessed at baseline and follow-up. For comparison we analysed 111 stable angina
      patients with stenting of single non-occlusive lesions. Over a period of 24 hours
      after PCI, CK-MB and cTNI were measured. RESULTS: CK-MB elevation after
      recanalisation of CTOs was observed in only 6% of patients with CTOs. The
      incidence of cardiac biomarker elevation was similar in patients with normal and
      severely impaired regional function, indicating that the low incidence was not
      due to a high prevalence of non-vital myocardium. In comparison CK-MB elevation
      after stenting of single non-occlusive lesions was observed in 13% of patients.
      In 14% of patients with CTOs and in 20% of patients with a single non-occlusive
      lesions cTNI increased after PCI. CONCLUSIONS: Despite the high plaque load of
      organised thrombotic material in CTOs, the incidence of cardiac biomarker
      elevation after recanalisation of CTOs was similar to that after stenting of
      single non-occlusive lesions. A specific adjunctive medical or interventional
      therapy may not be warranted during recanalisation of CTOs.

PMID- 19755267
TI  - The clinical outcome of restricting drug-eluting stents to patients at highest
      risk of restenosis.
AB  - AIMS: To assess the clinical outcomes of patients where drug eluting stents (DES)
      were restricted to those at highest risks of restenosis, we compared three
      different strategies for stent implantation: bare metal stents (BMS) only, DES
      only and a group where DES use was restricted (RES). METHOD AND RESULTS: Initial
      comparison was made between BMS only (279 patients, 316 lesions) and DES only
      (272 patients, 302 lesions). The endpoints of death, non-fatal myocardial
      infarction and target lesion revascularisation (TLR) [MACE] were assessed at 12
      months. The incidence of MACE in the BMS only and DES only groups were 14% and 7%
      (p=0.002) and TLR was 8% and 1% (p<0.0001). Comparison was then made between
      these results and a third group where DES was restricted to patients at highest
      risk of restenosis. The restricted group (RES) comprised 249 patients (271
      lesions) of which 53% received DES. RES remained significantly better than BMS,
      MACE (14% vs. 8%, p=0.02) and TLR (8% vs. 3%, p=0.02). When RES was compared with
      DES only, there was no significant difference in MACE (8% vs. 7% p=0.42), but
      there was a significantly lower TLR rate in the DES only group (1% vs. 3%
      p=0.04). CONCLUSIONS: The overall incidence of events in patients where DES use
      was restricted to 53% of patients remains low and this may be an acceptable
      treatment strategy to reduce costs.

PMID- 19755268
TI  - Histopathology of material captured by embolic protection device after
      percutaneous coronary interventions in atherosclerotic saphenous vein grafts.
AB  - AIMS: Different distal protections devices have been developed to prevent
      embolisation during percutaneous coronary intervention (PCI) in atherosclerotic
      saphenous vein grafts (SVG). The purpose of this descriptive study was to
      characterise the composition of material captured by embolic protection device
      from saphenous vein graft interventions by light and electron microscopy, to
      determine the age of the thrombotic component and to relate the pathological
      findings to the clinical condition, lesion characteristics and to the use of
      conventional or membrane covered self-expanding stents during the intervention.
      METHODS AND RESULTS: Forty consecutive patients treated with the FilterWire EX
      (Boston Scientific) during 42 SVG interventions were included. Plaque was found
      in 4.8%, thrombus in 16.7%, both plaque and thrombus in 69.0% of the filter bags,
      and 9.5% were empty. In 93% of the thrombus containing samples we found platelet
      aggregates that were formed within the last 10-15 minutes before fixation. This
      indicated platelet stimulation and aggregation during the PCI procedures. No
      relation was found between the composition of filter wire material and clinical
      condition, coronary lesion characteristics or the use of membrane covered self
      expanding stents (Symbiot(R)). CONCLUSION: The present study on material captured
      by embolic protein device after SVG interventions generated the hypothesis that
      these interventions were associated with acute platelet activation. In
      consequence, the use of glycoprotein IIb/IIIa inhibitors might be reconsidered in
      distal protected SVG interventions.

PMID- 19755269
TI  - Shear stress is associated with markers of plaque vulnerability and MMP-9
      activity.
AB  - BACKGROUND: Vulnerable plaque has been associated with local macrophage
      accumulation and local high matrix metalloproteinase-2 (MMP-2) and MMP-9
      activity. Since shear stress is a known local modulator of plaque location, we
      have determined whether local shear stress was associated with local plaque
      composition and with local MMP activity. METHODS AND RESULTS: In 17 NZW rabbits
      plaque was generated by denudation of the infrarenal aorta over a region of 5 cm
      and feeding them a high cholesterol diet for 2 months. After 2 months, a
      motorised IVUS pullback of the infrarenal aorta was performed with a 40 MHz IVUS
      catheter (CVIS, Boston Scientific, USA). IVUS derived vessel wall-lumen contours
      were reconstructed in 3D with in-house developed software. These reconstructions
      served as an input for a computational fluid dynamics technique, from which the 3
      D shear stress field was calculated. Plaque regions were divided in 5 regions
      (n=8) to identify the location of highest macrophage accumulation or selected on
      basis of shear stress to identify whether high shear stress selects macrophage
      accumulation (n=8). In a second series, shear stress values were used to select
      regions -containing both latent and active MMP-2 and MMP-9. Segments were
      sectioned with a microtome and stained for smooth muscle cells (SMC), macrophages
      (MPhi) and collagen (COL). MPhi, displayed the highest density upstream of the
      plaque (6.9+/-2.4%, p<0.05), while SMC accumulated downstream (74.8+/-1.9%) of
      the plaque. High shear stress was associated with MPhi accumulation and MMP-9
      activity (p<0.05). CONCLUSION: Upstream location of macrophages in plaques is
      associated with high shear stress and MMP-9 accumulation. These findings are
      discussed in relation to rheological theories reported previously in
      atherosclerosis.

PMID- 19755271
TI  - Principles of a self contained catheterisation laboratory based intravascular
      magnetic resonance system.

PMID- 19755270
TI  - First case of combined percutaneous aortic valve replacement and coronary artery
      revascularisation.

PMID- 19755272
TI  - Small 0.7 mm diameter laser catheter for chronic total occlusions, small vessels,
      tortuous anatomy, and balloon-resistant lesions - development and initial
      experience.
AB  - Excimer laser coronary atherectomy (ELCA) has been an FDA-approved treatment for
      coronary artery disease since 1992 and is commonly used as an adjunct treatment
      to balloon angioplasty. While ELCA presents a good therapeutic option for lesions
      non-dilatable or uncrossable with balloon angioplasty, historically the technique
      was not able to manage heavily calcified lesions. The advent of a smaller (0.9 mm
      tip diameter) excimer laser coronary catheter (Point 9, Spectranetics
      Corporation), capable of delivering higher energy densities and repetition rates,
      has proven effective and safe in the treatment of complex calcified lesions1-3.
      However, there is still a need for a smaller laser catheter for use in small
      vessels in other anatomical locations, balloon-resistant lesions, and for primary
      crossing of CTOs. We recently developed a new, even smaller over-the-wire (OTW)
      laser catheter (Point 7) capable of accessing the most distal vasculature and
      providing an additional margin of safety in treating complex lesions. Combined
      with a simple guidewire steering element this device could possibly be used to
      traverse the proximal cap of CTOs and assist in the primary crossing of the
      blockage.

PMID- 19755273
TI  - Tryton side-branch stent.

PMID- 19755274
TI  - Acute myocardial infarction due to spontaneous coronary artery dissection
      detected three days before by 64-slice spiral computed tomography.

PMID- 19755275
TI  - FDA panel, 7 and 8 December 2006 - The impact on our practice and research.

PMID- 19755276
TI  - Where the soul lives.

PMID- 19755277
TI  - Drug eluting stents in left main stem stenosis: patients will pay the price.

PMID- 19755278
TI  - Current controversies in carotid artery stenting.

PMID- 19755279
TI  - The balloon-expandable stent.

PMID- 19755280
TI  - The latest news from the European Association for Percutaneous Cardiovascular
      Interventions (EAPCI).

PMID- 19755281
TI  - Randomised comparison of Nobori, biolimus A9-eluting coronary stent with a
      Taxus(R), paclitaxel-eluting coronary stent in patients with stenosis in native
      coronary arteries: the Nobori 1 trial.
AB  - BACKGROUND: We studied the Nobori coronary stent coated with a bioabsorbable
      polymer and the anti-proliferative agent Biolimus A9 which may reduce neointimal
      formation. METHODS AND RESULTS: Patients undergoing percutaneous coronary
      intervention for de novo lesions in up to two native coronary arteries, in 29
      centres across Europe, Asia and Australia were randomly (2:1) assigned to receive
      the Biolimus A9 eluting stent Nobori (85 patients) or paclitaxel eluting stent
      Taxus(R) (35 patients). The two groups were well matched in baseline
      characteristics. The primary end point of non-inferiority for in-stent late loss
      of Nobori stent versus Taxus(R) stent, at 9 months, was reached with the values
      of 0.15+/-0.27 mm with Nobori stent and 0.32+/-0.33 mm with Taxus(R) stent
      (p=0.006). Neointimal volume obstruction was 2.2+/-6.0% and 8.9+/-9.2% for Nobori
      and Taxus(R) stent respectively (p=0.017). The rates of death, myocardial
      infarction and any target vessel revascularisation at 9 months were 0%, 4.7%, and
      7.1% respectively for Nobori stent, and 0%, 8.6% and 14.3% respectively for
      Taxus(R) stent. Clinically-driven target lesion revascularisation rate was 0% for
      Nobori stent and 2.9% for Taxus(R) stent. Stent thrombosis rates at 9 months were
      0% in both groups. CONCLUSIONS: In this trial the Nobori Biolimus A9 eluting
      stent proved to be safe and effective in reducing neointimal proliferation. The
      long term safety remains to be confirmed during the extended follow-up period of
      5 years.

PMID- 19755282
TI  - Revisiting the incidence and temporal distribution of cardiac and sudden death in
      patients undergoing elective intervention for unprotected left main coronary
      artery stenosis in the drug eluting stent era.
AB  - BACKGROUND: Whether restenosis remains a major, and potentially fatal,
      complication after percutaneous intervention for left main coronary artery (LMCA)
      stenosis and whether routine surveillance angiography should be a necessary part
      of the follow-up of these patients in current drug eluting stent (DES) era is
      largely debatable. METHODS AND RESULTS: Patients who underwent elective treatment
      of unprotected LMCA with DES in three referral centres in Europe were pooled as
      follows: i) 147 patients treated in Massy, between 12th August 2002 and 31st
      December 2004; ii) 107 patients, treated in Milan, San Raffaele Hospital and
      Columbus Clinic, between 16th April 2002 and 31st July 2004; iii) 86 patients
      treated at the Thoraxcenter, Rotterdam, between 16th April 2002 and 28th June
      2004 leading to a total of 340 elective consecutive patients. The rate of in
      hospital mortality was 0.6% (2/340). The out-of-hospital event rate in terms of
      cardiac death or myocardial infarction was 1.2% between discharge and 3 month,
      0.6% between three and 6 months and 0.6% between 6 months and 1 year. Two (0.6%)
      sudden and unexpected deaths were cumulatively observed, at 8 days and 2 months
      after intervention, respectively. The rate of confirmed or possible stent
      thrombosis was 0.9%. At 1 year, the out-of-hospital cumulative incidence of
      cardiac death or MI was 2.4%. In the cohort of patients who refused to undergo
      angiographic surveillance, no death and no MI occurred. CONCLUSIONS: Cardiac and
      sudden death and the incidence of stent thrombosis after LMCA intervention with
      DES were reasonably low and compared favourably with what reported in non-LMCA
      lesions. At the time intimal hyperplasia is expected to peak (i.e. beyond 6
      months), no increase of adverse events, in terms of death or myocardial
      infarction was observed.

PMID- 19755283
TI  - Endovascular therapy of chronic mesenteric ischaemia.
AB  - BACKGROUND: Chronic mesenteric ischaemia (CMI) is associated with a high
      morbidity and mortality. Most likely causes of CMI are atherosclerosis, external
      compression (Dunbar Syndrome) and vasculitis. We report on our experience with
      endovascular stent therapy. PATIENTS AND METHODS: Between Sept. 1998 and Dec.
      2005 we treated 21 consecutive patients (52% male; mean age 64+/-15 years, range
      18-81 years) due to symptomatic CMI. A total of 34 interventions with 41 treated
      lesions were performed. Aetiology of vessel obstruction was atherosclerosis in 14
      patients (67%), Dunbar syndrome in 3 patients (14%), chronic type B aortic
      dissection in 2 patients (9%), Takayasu's arteritis in 1 patient (4.5%), external
      compression following abdominal surgery in 1 patient (4.5%). Target lesions were
      celiac trunk (n=16), superior mesenteric artery (n=24), and inferior mesenteric
      artery (n=1). Twenty-two percent (n=9) of the lesions were total occlusions. The
      patients underwent serial follow-up duplex examinations before discharge and
      every 6 months thereafter or in case of symptom recurrence. RESULTS: Thirty-one
      of the 34 (91%) interventions were technically successful (37/41 lesions; 90%).
      Two of these 4 lesions were treated successfully using another approach in a
      second intervention. Brachial access was used in 16/34 cases (47%). One or more
      stents were placed in 29/34 interventions (85%) and 35/41 lesions. In 3 cases, in
      stent restenosis was treated with balloon angioplasty alone, and in two cases, 3
      occlusions could not be reopened. During 6 interventions, drug eluting stents
      were placed. All patients treated successfully were free of symptoms immediately
      after the intervention with recurrence of symptoms in case of restenosis. After a
      mean follow-up of 31+/-26 (range 0-87) months restenosis was detected in 6
      patients (29%). Two major complications occurred which were treated without
      permanent sequelae. CONCLUSION: Stenoses of mesenteric arteries resulting in
      symptomatic CMI can be treated successfully with stent-angioplasty; for
      anatomical reasons, the brachial approach should be considered. Recanalisation of
      total obstructions is feasible if a stump of the occluded artery is detectable.
      Restenosis is frequent and can easily be treated with balloon angioplasty or
      stent-in-stent placement.

PMID- 19755284
TI  - Predicting coronary artery bypass graft surgery in acute coronary syndromes.
AB  - AIMS: To identify features predictive of hospital coronary artery bypass graft
      (CABG) surgery in patients with acute coronary syndromes (ACSs). METHODS AND
      RESULTS: Data from 17,434 patients enrolled in an observational study were
      analysed. Patients in private hospitals were more likely to undergo CABG than
      those in public hospitals (10.3% vs. 6.9%, P<0.01); CABG was more frequent in the
      USA than in Europe (11.9 % vs 3.5%, P<0.01). Clinical features independently
      predictive of CABG on multivariable analysis included no previous CABG, male sex,
      history of angina, hypertension, hyperlipidaemia, or diabetes, no history of
      atrial fibrillation or congestive heart failure, ST depression in multiple
      territories, and absence of ST elevation. These factors were assigned a score to
      quantify the likelihood of CABG (c-statistic 0.69). This score was predictive
      regardless of ACS subgroup (c-statistic 0.65-0.71) and remained predictive across
      institutions regardless of the frequency with which CABG was performed. The score
      was of greatest clinical utility among hospitals performing CABG in >10% of their
      ACS patients. CONCLUSIONS: Identifying ACS patients likely to undergo CABG using
      clinical features alone remains difficult. In hospitals with higher rates of
      surgical revascularisation, a subgroup of patients with an approximate 30%
      likelihood of CABG can be identified. Therapy in these patients can be tailored
      to minimise bleeding risk without compromising outcomes.

PMID- 19755285
TI  - The sirolimus-eluting coronary stent in clinical practice: impact of direct
      stenting versus stenting with balloon pre-dilatation.
AB  - AIMS: When using bare metal stents (BMS), direct stenting (DS) has become an
      established method for percutaneous coronary interventions (PCI). If drug-eluting
      stents are used, DS is currently not recommended. METHODS AND RESULTS: We
      analysed the data of the German Cypher Stent Registry to evaluate current use and
      outcome of DS using the sirolimus-eluting stent (SES). 4,437 patients at 122
      hospitals who received a single SES for one lesion and completed follow-up, were
      included. DS was performed in 1,727 (38.9%) of these patients. However, there was
      a wide range from 0% to 77.8% within the centres. The following factors were
      independently associated with the use of DS: degree of stenosis (per 10%)
      (p<0.0001), type C lesion (p<0.0001), three vessel disease (p<0.0001), age (per
      decade) (p<0.0001), target vessel = LAD (p=0.0029), diabetes mellitus (p=0.0222)
      and renal insufficiency (p=0.0260). There were no higher event rates for DS
      compared to predilatation from admission until the end of follow-up: death rates
      were 1.4% versus 1.9%, p=0.1854, TVR rates 7.9% versus 8.7%, p=0.3388 and TVR or
      MACCE rates 10.8% versus 12.1%, p=0.2088. This was confirmed after correction for
      confounding factors. CONCLUSIONS: In current clinical practice DS with the SES is
      performed within a very wide range at the different hospitals. Further predictors
      for the use of DS with the SES are similar to those known from BMS. DS with the
      SES in such selected patients seems to be safe and effective.

PMID- 19755286
TI  - Advantage of sirolimus-eluting stents compared to intracoronary radiation therapy
      30 months after treatment of in-stent restenosis.
AB  - AIMS: Sirolimus-eluting stents (SES) have been shown during short follow-up
      periods to be effective for treatment of in-stent restenosis (ISR). This study
      evaluated the 30-months clinical efficacy after SES for treatment of ISR in
      comparison with intracoronary radiation therapy (IRT). METHOD AND RESULTS:
      Seventy-two consecutive ISR lesions in native coronary arteries (<30 mm lesion
      length, reference diameter <3.5 mm) of 72 patients were treated with SES. SES
      were used in 16 lesions after failed IRT and in 56 lesions for first time ISR.
      Seventy-two patients with 72 lesions from a prospective registry of 141 patients
      treated with IRT (beta-radiation) were matched for diabetes, reference vessel
      diameter, lesion length, and pattern of ISR to present the control group. At 6
      months in-stent late loss was 0.29+/-0.48 vs 0.53+/-0.63 mm for the SES group
      compared to the IRT group (p=0.025). Target lesion revascularisation (TLR) at 12
      month follow-up was performed in 7 lesions (10%) after SES and in 17 lesions
      (24%) after IRT (P=0.025). TLR rate at 30-months was 13% in the SES group vs 32%
      in the IRT group (P=0.008). MACE (death, myocardial infarction, target lesion
      revascularisation) at 30-months was observed in 13 patients (18%) in the SES
      group and in 25 patients (35%) in the IRT group (P=0.024). Considering only
      patients treated with SES for first-time ISR, TLR rate was 3.5% at 30-months. In
      the 16 patients treated with SES after failed IRT TLR rate was 44% at 30-months.
      CONCLUSIONS: Thirty month clinical follow-up of patients treated with SES for
      first time ISR is favourable compared to follow-up after IRT. However, use of SES
      after IRT failure is associated with a high rate of recurrent and potentially
      late treatment failure.

PMID- 19755287
TI  - Percutaneous treatment of multivessel coronary disease in the drug eluting stent
      era: comparison of bare-metal stents, drug-eluting stents and a mixed approach in
      a large multicentre registry.
AB  - BACKGROUND: Restenosis and a high incidence of new revascularisations reduce the
      long-term efficacy of percutaneous coronary intervention (PCI) in patients with
      multivessel coronary artery disease. AIMS: To determine the modality of
      utilisation and the clinical efficacy of drug eluting stents (DES) in a real
      world multivessel PCI scenario. METHODS: From July 2002 to December 2004, 1726
      consecutive patients enrolled in the REAL Registry (Registro REgionale
      AngiopLastiche Emilia-Romagna) underwent elective multivessel PCI with multiple
      stents in at least two different vessels; among them, 939 (54%) received only
      bare-metal stents (BMS group), 288 (17%) only DES (DES group) and 499 (29%) were
      treated with BMS and DES in different vessels (MIX group). The incidence of major
      adverse cardiac events (MACE= death, myocardial infarction and target vessel
      revascularisation) during follow-up was assessed. RESULTS: Patients in the BMS
      group were older, diabetes was more frequent in the DES and MIX groups, while
      more lesions and more often a three vessel treatment was performed in the MIX
      group. In the DES group, lesions were longer, in smaller vessels and more often
      in the left main compared with BMS and MIX groups. In the MIX group too, lesions
      treated with DES were at higher risk for restenosis than those treated with BMS.
      Procedural success was similar in the three groups (98.9%). Notwithstanding the
      different risk profile, 12-month follow up did not show differences in clinical
      end points among the three groups. Multivariate analysis indicated that age, a
      modified Charlson's comorbidity index and diabetes were independent predictors of
      death or AMI; total lesion length, use of only DES or MIX approach and treatment
      of left main were predictors of TVR, while left main treatment along with only
      DES use, modified Charlson's index and reference vessel diameter independently
      affected the incidence of MACE. Use of at least one DES reduced the risk of TVR
      by 37% and MACE by 29%, while DES in every lesion treated reduced TVR risk by 37%
      and MACE by 39%. CONCLUSIONS: In this large multicentre registry, DES were
      utilised in only half of the multivessel PCI procedures, mainly to treat high
      risk patients and lesions. However, this selective use of DES was independently
      associated with a lower incidence of 1-year TVR and MACE. Whether increasing the
      rate of DES utilisation would further improve the clinical outcome remains to be
      investigated.

PMID- 19755288
TI  - The impact of age and Killip class on outcomes of primary percutaneous coronary
      intervention. Insight from the PRAGUE-1 and -2 trials and registry.
AB  - BACKGROUND: Primary PCI (p-PCI) was shown to be the most effective reperfusion
      strategy for ST segment elevation myocardial infarction (STEMI). However, its
      success rates and clinical outcomes among the elderly patients are less well
      defined. The aim of this work was to access, whether primary PCI, as compared to
      thrombolysis, improves the outcomes of elderly patients with STEMI to the same
      extent as in the younger patient groups and whether this holds true also for the
      elderly patients presenting in cardiogenic shock or acute heart failure.
      PATIENTS: A total of 2,073 patients were analysed: 1,050 were enrolled in the
      randomised trials PRAGUE-1 and -2 and 1,023 entered a p-PCI registry at our
      institution. The mean age was 64 years, 29% were females. Three hundred and
      ninety patients were in the elderly (> 75 years) age group, 605 patients were
      aged 65-74 years and 1,078 patients were <65 years old. Acute heart failure was
      more prevalent in the patients that entered in the registry as compared to the
      randomised patients: Killip class IV 10% vs 1% (p < 0.001), Killip II-III class
      29% vs 18% (p < 0.001). RESULTS: An optimal PCI result was achieved in 81% of the
      elderly and 90% of the younger patients (p < 0.001). The absolute mortality
      reduction by p-PCI compared to thrombolysis was 5.7% in the elderly and 3.7% in
      the younger groups (n.s.). The in-hospital mortality of Killip IV patients was
      69% (elderly group), 54% (group 65-74 years, p < 0.001) and 27% (group <65 years,
      p < 0.001). The in-hospital mortality of patients without cardiogenic shock was
      low in all age groups: 4% (elderly), 2.7% (65-74 years) and 0.8% (<65 years).
      CONCLUSION: Primary PCI is the most effective reperfusion strategy for the
      elderly patients presenting with STEMI.

PMID- 19755289
TI  - Comparison of the in vitro performance of 6 and 7 French aspiration catheters.
AB  - OBJECTIVE: A comparison of aspiration catheters that have been approved for real
      world use was carried out in vitro. BACKGROUND: Myocardial damage occurs during
      therapeutic aspiration of thrombus. The relative efficiency of aspiration may be
      important in this regard. METHODS: Using saline and human clot, nine aspiration
      catheters were compared Thrombuster III(R)N (6 Fr and 7 Fr), ZEEK (6 Fr), Rebirth
      (7 Fr), Eliminate (6 Fr and 7 Fr), Pronto (6 Fr), and Export(R) (6 Fr and 7 Fr).
      Tracking was assessed from the resistance required to pass the catheter through a
      vessel model. Pushability was determined from the difference between the load at
      the hand piece and tip of the catheter during advancement through the vessel
      model. RESULTS: The Thrombuster III(R)N (6 Fr and 7 Fr) showed significantly
      better aspiration performance, although the ranking order of the catheters was
      not the same for saline and clot. The Thrombuster III(R)N also showed the best
      tracking with low resistance and was the easiest catheter to advance, as
      evaluated based on pushability. CONCLUSIONS: In the present in vitro evaluation
      system, the Thrombuster III(R)N performed better than other catheters.

PMID- 19755290
TI  - A simple risk score for prediction of mortality in patients undergoing
      percutaneous coronary intervention (PCI) for non-ST segment elevation acute
      coronary syndromes (NSTEACS).
AB  - AIMS: To develop an easily applicable prognostic model that can predict mortality
      risk in patients undergoing percutaneous coronary intervention (PCI) for non-ST
      segment elevation acute coronary syndromes (NSTEACS). METHODS AND RESULTS: A
      retrospective analysis of 630 consecutive patients undergoing PCI for NSTEACS at
      our institution between January 1999 and December 2000 (development phase).
      Multivariate logistic regression analysis to identify independent predictors of
      mortality. Development of a 'weighted' and an 'unweighted' risk prediction model,
      each including the following 8 parameters: age > 65 years, age >75 years, left
      ventricular systolic function (LVEF) <50%, renal impairment (serum creatinine >
      200 mmol/L), multi-vessel (3 vessel) disease, peripheral vascular disease,
      diabetes mellitus and female gender. Validation of the predictive model on the
      following 500 patients that underwent PCI over a 20 month period (validation
      phase). Prognostic models tested for their ability to predict mortality. The
      derived model was applied to the validation group and the area under receiver
      operating characteristic curves (ROC) was used to estimate the predictive ability
      of the prognostic models. The area under the ROC curve on the validation phase
      was 0.835, signifying a good ability to predict 30 day mortality following PCI.
      CONCLUSION: We have derived a simple easily applicable predictive model based on
      readily available information that can predict mortality following PCI for
      NSTEACS.

PMID- 19755291
TI  - True percutaneous implantation of the CoreValve aortic valve prosthesis by the
      combined use of ultrasound guided vascular access, Prostar(R) XL and the
      TandemHeart(R).

PMID- 19755292
TI  - Axxess Biolimus A9(R) eluting bifurcation stent system.

PMID- 19755293
TI  - Abbott Vascular's everolimus eluting side branch access stent.

PMID- 19755294
TI  - Late stent thrombosis: the Damocle's sword of drug eluting stents?
AB  - As a result of the introduction of drug eluting stents (DES) to clinical
      practice, angiographic and clinical parameters of restenosis have been
      significantly improved. However, several recent publications have raised concerns
      about long-term safety of this technology. They include a potential risk of
      inducing chronic inflammation within the coronary artery, delayed healing and
      late stent thrombosis.Recently, late stent thrombosis, a rare but often life
      threatening event, has been reported to occur more frequently following DES
      placement. The mechanism of this phenomenon has not been fully elucidated.What is
      the true incidence of stent thrombosis after DES therapy? Is it similar or higher
      than with bare metal stents? Are randomised trials with DES therapy
      overestimating the benefits of this therapy? Which are the potential limitations
      of these studies? Are DES increasing rates of death and myocardial infarction
      from randomised trials and registries a true fact? In the following pages we
      review recently reported data about DES suggesting potential safety concerns
      associated with the current widespread use of DES.

PMID- 19755295
TI  - Bifurcated stents: giving to Caesar what is Caesar's.

PMID- 19755296
TI  - The evolving role of coronary angiography and fluoroscopy in cardiac diagnosis
      and intervention.
AB  - In the era of drug-eluting stents that have dramatically reduced the re-stenosis
      rate, and in the context of the development of emerging modalities like magnetic
      resonance imaging (MRI) and multislice computed tomography that allow precise and
      non-invasive diagnosis, it becomes important to question whether and how
      fluoroscopic-based evaluation of cardiac structure and function shall evolve.
      Indeed, this widely used technique is also known for its invasiveness, risk of
      ionising radiation effects, and projection imaging limitations.In order to answer
      this question it is important to understand the technological advances under
      development for fluoroscopy and link them with the unmet clinical needs of today
      in the field of both diagnostic and interventional coronary procedures. It can
      then be understood how fluoroscopic-based technologies can meet these needs. This
      discussion shall review the emerging technologies available in the cath lab and,
      in doing so, portray a concept for the next generation catheterisation
      laboratory.

PMID- 19755297
TI  - Left ventricular angiogram in a patient with noncompaction cardiomyopathy.

PMID- 19755298
TI  - Editorial.

PMID- 19755300
TI  - What is the outcome of mother and child after percutaneous mitral valvuloplasty
      performed during pregnancy?

PMID- 19755299
TI  - Everolimus eluting stents: beyond targeting restenosis!

PMID- 19755301
TI  - You ain't seen nothing yet...

PMID- 19755302
TI  - European Association of Percutaneous Cardiovascular Interventions (EAPCI).

PMID- 19755303
TI  - A randomised comparison of an everolimus-eluting coronary stent with a paclitaxel
      eluting coronary stent:the SPIRIT II trial.
AB  - BACKGROUND: Everolimus has been successfully tested in humans using both an
      erodable and a durable polymer in small previous studies. METHODS: This single
      blind multi-centre non-inferiority randomised (3:1) controlled trial evaluated
      the safety and performance of the XIENCE V Everolimus Eluting Coronary Stent
      System (XIENCE V EECSS) versus the TAXUS Paclitaxel Eluting Coronary Stent System
      (TAXUS(R) PECSS) in the treatment of patients with a maximum of two de novo
      native coronary artery lesions located in two different epicardial vessels. Three
      hundred patients with evidence of myocardial ischaemia were allocated to stent
      implantation with an everolimus-eluting stent (n=223) or a paclitaxel-eluting
      stent (n=77). Suitable lesions had a diameter stenosis of <50-99%, a length of
      <28 mm, and a reference vessel diameter between 2.5 mm and 4.25 mm. The primary
      endpoint was in-stent late loss (LL) at 180 days. Percentage in-stent volume
      obstruction (%VO) was measured by intravascular ultrasound (IVUS) in a subset of
      152 patients. Clinical secondary endpoints included ischaemia driven major
      adverse cardiac events (ID-MACE) at 180 days. RESULTS: At 6 months, the in-stent
      LL was 0.11+/-0.27 mm in the everolimus-eluting stent arm, as compared to 0.36+/
      0.39 mm in the paclitaxel-eluting stent arm (p<0.0001). Percentage VO in the
      everolimus-eluting stent arm was 2.5+/-4.7% versus 7.4+/-7.0% in the paclitaxel
      eluting stent arm (p<0.0001). Hierarchical MACE was 2.7% (6/222) in the
      everolimus-eluting stent arm vs. 6.5% (5/77) in the paclitaxel-eluting stent arm.
      CONCLUSION: This non-inferiority randomised trial not only met its primary
      endpoint, but also demonstrated the superiority of the everolimus-eluting stent
      over the paclitaxel-eluting stent in terms of in-stent late loss.

PMID- 19755304
TI  - The randomised study of the double dose versus single dose sirolimus-eluting
      stent for the treatment of diabetic patients with de novo coronary lesions.
AB  - BACKGROUND: Even though sirolimus-eluting stents (SES) have been shown to
      significantly improve binary restenosis and target lesion revascularisation rates
      (TLR) compared to bare metal stents in diabetic patients, the revascularisation
      rate is still higher than those of non-diabetics. Whether a double dose (DD) of
      sirolimus on a stent would provide a greater reduction in neointimal hyperplasia
      compared to single dose (SD) SES in de novo coronary lesion of diabetic patients
      is unknown. METHODS AND RESULTS: A total of 56 patients (58 lesions) were
      prospectively randomised in a double blind fashion in a 1:1 ratio to SD (30
      lesions) versus DD (28 lesions). Procedure success was achieved in all patients.
      QCA results at 6 months were comparable between groups, including the primary
      endpoint of in-stent late lumen loss (0.19+/-0.29 mm in SD versus 0.18+/-0.33 mm
      in DD, p=0.96). Furthermore, restenosis was not found inside the stent in either
      group. By IVUS, there was no late/acquired incomplete stent apposition at follow
      up, and% neointimal volume was 2.2+/-1.8% in SD versus 1.7+/-2.0% in DD, p=0.44.
      At 1-year clinical follow-up, there was no significant difference between groups
      for major events, including TLR which occurred in 1 patient in SD versus 3
      patients in DD, p=0.61. Overall, there was only 1 subacute stent thrombosis (DD
      arm), and no late thromboses. CONCLUSIONS: Double dose SES did not improve the
      prevention of neointimal proliferation in diabetic patients with de novo coronary
      lesion compare to single dose SES.

PMID- 19755305
TI  - Long term outcome of balloon mitral commissurotomy during pregnancy: a
      prospective physical and mental evaluation of babies.
AB  - AIM: The immediate and long-term results of balloon mitral commissurotomy (BMC)
      during pregnancy were evaluated in patients and in their babies looking for
      radiation side effects. METHODS AND RESULTS: Sixty one patients (mean age: 28.5+/
      5.0 years) had BMC at a mean age of gestation of 26.8+/-5.5 weeks. The procedure
      was successful in all patients except in one who had a severe mitral
      regurgitation and subsequent mitral valve replacement (MVR). All patients
      delivered at term vaginally in 58 (95.1%) cases. There was only one death in a
      patient who delivered at home. At a mean follow-up of 66.8+/-36.0 months, 4
      patients had MVR, the remaining were in NYHA class I/II. Restenosis was found in
      4 (7.2%) patients. The 63 babies (two gemellar pregnancies) had a normal weight
      of birth except of one case of hypotrophy. At a mean follow-up of 64.5+/-32.5
      months, two babies died, 1 had hypotrophy, 2 had microcephaly, 8 had an IQ < 70
      but none had a severe mental retardation (IQ <34). None of these events were
      radiation related. CONCLUSION: BMC is the procedure of choice in pregnant
      patients with mitral stenosis. No late radiation side effects were observed in
      children but longer follow-up is required.

PMID- 19755306
TI  - Biodegradable-polymer-based, paclitaxel-eluting Infinnium stent: 9-Month clinical
      and angiographic follow-up results from the SIMPLE II prospective multi-centre
      registry study.
AB  - BACKGROUND: SIMPLE II was a multi-centre, prospective registry study aimed at
      investigating the safety and efficacy of the Infinnium (Sahajanand Medical
      Technologies Pvt. Ltd, India) paclitaxel-eluting stent for the treatment of
      single de novo lesions in the native coronary arteries. METHODS: One hundred and
      three patients with symptomatic coronary artery disease were treated for single
      de novo native coronary artery lesions using the Infinnium stent (paclitaxel
      concentration 1.4 mcg/mm2 released over 48 days) in a multi-centre, prospective
      study performed on 3 continents (Asia, Europe and South America). The primary
      safety endpoint was major adverse cardiac events at 30 days (MACE 30d) and
      efficacy was assessed by in-stent binary restenosis as measured by quantitative
      coronary angiography (QCA) at six-month follow-up. A clinical follow-up was
      scheduled at nine months. RESULTS: The mean patient age was 58.5 years; 70.9%
      were males; 43.7% had unstable angina and 38.8% previous myocardial infarction.
      Risk factors included hypertension in 62.1%, hypercholesterolemia in 52.4%,
      current smoking in 32.0% and diabetes in 28.2%. Stent implantation was successful
      in all patients, with more than one stent being implanted in 9 patients (8.7%).
      Hierarchical MACE 30d was 2.9%. At nine months, 101 patients had clinical follow
      up (1 patient had died and 1 refused). There was one death (1.0%), one Q-wave
      myocardial infarction (Q MI) (1.0%), three non-Q MIs (2.9%), one clinically
      driven target lesion Coronary Artery Bypass Grafting (CABG) (1.0%), and one
      clinically-driven target lesion repeat percutaneous coronary intervention (re
      PCI) (1.0%). The overall event-free rate at nine months was 93.2%. QCA revealed
      in-stent and in-segment late loss of 0.38+/-0.49 mm and 0.18+/-0.46 mm, resulting
      in binary restenosis rates of 7.3% and 8.3%, respectively. There was one case of
      late stent thrombosis in the patient experiencing the Q MI and subsequent re-PCI.
      CONCLUSIONS: The Infinnium paclitaxel-eluting stent appears to be safe and
      efficacious for the treatment of single de novo lesions in coronary arteries in a
      patient population with symptomatic coronary artery disease (CAD).

PMID- 19755307
TI  - Catheter closure of paravalvular leak.
AB  - AIMS: The purpose of this study was to evaluate the feasibility and short-term
      efficacy of transcatheter paravalvular leak closure using different occlusion
      devices. METHODS AND RESULTS: Twenty-one patients underwent transcatheter closure
      of either aortic or mitral paravalvular leak from June 2002 to February 2006
      using the Amplatzer PDA, ASD or VSD occluder. All patients had symptoms and signs
      of haemolysis and/or cardiac decompensation with dyspnoea.Implantation of a
      device was technically successful in twenty patients (95%). Immediate residual
      leak was found in seventeen patients (85%). Significant shunting persisted in
      nine cases during follow up (45%).Permanent leaflet obstruction was observed in
      one patient. Severe complications during follow up led to early death in one
      patient and surgical intervention in three. A successful second catheter
      treatment was performed in another three patients. The event-free survival from
      re-operation, death and stroke at the end of the observation period was 80%.
      CONCLUSION: Transcatheter closure of paravalvular leaks is a technically
      feasible, but demanding procedure. Residual leaks are common and may worsen pre
      existing haemolysis. Due to the significant ongoing morbidity in this group of
      patients and the complexity of follow up individual patient results differ
      considerably. Nevertheless, it is possible to achieve some symptomatic relief,
      thus an interventional approach should be discussed as a potential treatment
      option for those patients with a limited defect and who are not deemed suitable
      for another operation.

PMID- 19755308
TI  - Percutaneous Patent Foramen Ovale (PFO) closure in young patients with both
      cryptogenic brain infarction and PFO associated with Atrial Septal Aneurysm
      (ASA).
AB  - BACKGROUND: To assess the safety and efficacy of percutaneous patent foramen
      ovale (PFO) closure for the prevention of recurrent stroke in high-risk patients.
      METHODS AND RESULTS: Between January 2002 and March 2005, 40 patients (65%
      female), mean (SD) age 43 (10) years were identified using the following
      inclusion criteria: <60 years, recent brain infarction (<3 months), combination
      of PFO plus atrial septal aneurysm (ASA) and exclusion of any other
      thromboembolic cause. Percutaneous PFO closure was performed under general
      anaesthesia and under the guidance of transoesophageal echocardiography (TEE).
      Aspirin and clopidogrel were given for three months after PFO closure, followed
      by aspirin alone. Neurological examination was performed every three months.
      RESULTS: PFO closure was successful in all patients, using all devices: INTRASEPT
      in 34 cases, STARFlex in 5 cases and AMPLATZER in one case. At day one,
      transthoracic echocardiography (TTE) excluded malpositioning of the device or
      pericardial effusion. At 6 months, TTE and TEE confirmed satisfactory
      implantation of the device, with no spontaneous shunt. No device related thrombi
      was observed. Mean patient follow-up was 17+/-7 months (range 12-38) and was 100%
      complete. No patients suffered from recurrent stroke (neither transient ischaemic
      attack nor brain infarction). CONCLUSION: This preliminary experience is
      encouraging for PFO closure with a 0% risk of stroke recurrence rate in a high
      risk subset of patients (< 60 years, recent cryptogenic stroke, PFO plus ASA) and
      is safe using the current technology. Larger series with longer follow-up and
      randomised studies are still necessary in this setting before the completion of
      guidelines.

PMID- 19755309
TI  - Two-year clinical follow-up of the unrestricted use of the paclitaxel-eluting
      stent compared to the sirolimus-eluting stent as part of the Taxus-Stent
      Evaluated at Rotterdam Cardiology Hospital (T-SEARCH) registry.
AB  - AIMS: To investigate the medium term (2 year) clinical outcome of the use of the
      paclitaxel-eluting stent (PES) compared to the sirolimus-eluting stent (SES). To
      date, there are no direct comparative data on the efficacy of these stents over
      medium term follow-up. Furthermore, a possible late restenotic phenomenon has not
      been excluded. METHODS AND RESULTS: The Taxus-Stent Evaluated At Rotterdam
      Cardiology Hospital (T-SEARCH) registry compared 576 consecutive "all-comer"
      patients, exclusively treated with PES, with 508 patients who received SES from
      the RESEARCH registry in the preceding period. Patients were enrolled
      irrespective of clinical or angiographic features. At 2 years, major adverse
      cardiac event (death, myocardial infarction or target vessel revascularisation)
      rates were comparable in the two groups: 15.4% in the SES group versus 18.9% in
      the PES group (HR 1.26, 95% CI 0.94-1.69, p=0.12). Correcting for differences in
      both groups resulted in an adjusted HR of 1.11 (95% CI 0.82-1.50, p=0.51, using
      significant univariate variables). Target vessel revascularisation was 8.0% in
      the SES group compared with 9.6% in the PES group (HR 1.23, 95% CI 0.81-1.86,
      p=0.33). CONCLUSIONS: The unrestricted use of SES and PES was safe at two years
      of follow-up. No significant difference was found between the two devices in
      terms of death or MI, MACE, TVR or TLR. No late clinical restenotic phenomenon
      was observed.

PMID- 19755310
TI  - Virtual histology and remodelling index allow in vivo identification of allegedly
      high-risk coronary plaques in patients with acute coronary syndromes: a three
      vessel intravascular ultrasound radiofrequency data analysis.
AB  - BACKGROUND: Virtual histology (VH) uses intravascular ultrasound (IVUS)
      radiofrequency spectral analysis to locally identify the morphology and
      composition of atherosclerotic plaques. We sought to explore in vivo the relation
      between IVUS-derived thin cap fibro-atheroma (IDTCFA) and remodelling index in
      patients with acute coronary syndromes using IVUS-VH. METHODS AND RESULTS: Twenty
      one patients (63 vessels) were enrolled. When compared to cross sectional areas
      (CSAs) without necrotic core in contact with the lumen (NCCL), CSAs with NCCL had
      a larger plaque burden 42.8+/-11.5% vs. 32.8+/-11.5%, p<0.001; higher overall
      necrotic core content [13.8+/-10.7% vs. 2.3+/-7.9% (p<0.001)] and calcified
      tissue [4.7+/-6.5 vs. 0.66+/-2.1% (p<0.001)]. On average there were 2 IVUS
      derived thin cap fibro-atheroma (IDTCFA) per patient. Nearly half of the IDTCFAs
      had positive remodelling. CONCLUSIONS: CSAs with NCCL had worse morphological
      profiles than those with no NCCL. The simultaneous and more detailed assessment
      of IDTCFA and remodelling index identifies a reduced number of allegedly high
      risk plaques. The findings of this study may have important clinical
      implications, since they shed light into a possible method of identiying
      potentially high-risk plaques suitable for pharmacological and/or local
      treatment.

PMID- 19755311
TI  - Human myocardium preconditioning during successive balloon inflations: irrelevant
      influence of both collateral recruitment and clinical pre-intervention
      interference.
AB  - AIMS: We hypothesised that ischaemic preconditioning (IP) results from complex
      cellular mechanisms without significant collateral recruitment or clinical pre
      intervention interference. METHODS AND RESULTS: A total of 58 patients underwent
      three 2-min balloon inflations separated by 5-min reperfusions. Anginal symptoms
      were graded according to this scale: 0 = absent, 1 = mild, 2 = moderate and 3 =
      severe. ST-segment shift and QT dispersion (QTd) were measured from 12 lead ECGs.
      Ejection fraction (EF) was assessed by 2D echo and collateral flow recruitment by
      collateral flow index (CFI). Anginal scores were 2.4+/-0.6, 1.7+/-0.5 and 1.2+/
      0.6 (p<0.05); ST-segment shifts were 6.0+/-2.1, 3.8+/-1.8, and 1.9+/-1.2 mm
      (p<0.05); QTd increased from a baseline value of 39+/-24 to 96+/-27 (p<0.05) and
      decreased to 66+/-23 and 45+/-16 ms, at the end of the first, second and third
      inflation, respectively. EF decreased from a baseline value of 63+/-3% to 33+/
      2%, 34+/-3%, and 36+/-5% in the three inflations. The CFI was approximately 0.15
      in all ischaemic periods. CONCLUSION: These results suggest that IP does occur
      during repeated brief coronary artery occlusion in patients with a low likelihood
      of both collateral recruitment and clinical pre-intervention interference.

PMID- 19755312
TI  - Incidence of procedural related myocardial infarction following percutaneous
      coronary intervention. A matter of definitions.
AB  - AIM: To define the incidence of procedural related myocardial infarction (MI) in
      patients undergoing elective PCI using different definitions of MI, especially
      focusing on the criteria proposed by the European Society of Cardiology (ESC) and
      the American College of Cardiology (ACC) for the definition of MI. METHODS AND
      RESULTS: A prospective study including 220 patients scheduled for elective PCI.
      To be included, preprocedural values of the following biochemical markers had to
      be normal; aspartate aminotransferase (AST), creatine kinase (CK) , creatinine
      kinase MB fraction (mass concentration) (CK-MBmass) and cardiac troponin I
      (cTnI).According to different definitions the incidence of procedural related MI
      following PCI differed from 0,9% (previous WHO definition) to 26,4% (ESC/ACC
      criteria). Other commonly used definitions of MI resulted in incidence rates
      between these values. CONCLUSIONS: Depending on definitions used the incidence of
      procedural MI following elective PCI may vary by a factor of 30. This makes
      comparison of MI rates between institutions difficult. Furthermore, outcome and
      conclusions in interventional studies with MI as an endpoint may differ according
      to definitions used for procedural MI. A clear description of the applied
      definition of procedural MI following PCI is mandatory. For epidemiological and
      other reasons a separate ICD code is proposed for MIs caused by PCI.

PMID- 19755313
TI  - Sirolimus-Eluting Stents vs Bare Metal Stents for the treatment of unprotected
      left main coronary artery stenosis.
AB  - AIM: This study compares the clinical and angiographic outcomes of sirolimus
      eluting stent (SES) and bare metal stent (BMS) implantation for unprotected left
      main coronary artery (ULMCA) stenosis. METHODS AND RESULTS: We analysed 141
      unselected patients with unprotected LMCA stenosis: 72 were treated with SES and
      69 with BMS. SES patients were younger, with a higher ejection fraction, had more
      often hypertension, family history and were more often smokers. The procedural
      success rate was 94.2% in SES group and 87% in BMS group. In SES group there were
      2 periprocedural myocardial infarction (3%). 1 intra-procedural death (1.4%) and
      1 in-hospital death (1.4%) and respectively 2 (3%),4 (6%) and 3 (4%) in BMS
      group. No incidents of stent thrombosis, stroke and emergent CABG occurred during
      hospitalisation in either group. SES patients showed a lower late lumen loss
      (0.5+/-0.8 mm vs 1.1+/-1.0 mm; p<0.05) and a lower nine-month angiographic
      restenosis rate (13.6% vs 24.3%; p=NS). The MACE free survival rate at 2 years
      was 83% in the SES group vs 55% in the BMS group (p<0.001). CONCLUSIONS: SES
      implantation for unprotected LMCA stenosis in "real world" population appears
      safe with a low restenosis and MACE rate at follow-up.

PMID- 19755314
TI  - Coronary perforations.
AB  - Coronary artery perforation is a serious complication of percutaneous coronary
      intervention (PCI). This review summarises the aetiology, incidence, current
      existing therapeutic options and outcome of coronary perforations given the
      advance in interventional techniques, devices and use of glycoprotein inhibitors
      (GP IIb/IIIa). Perforations are classified as Type 1, 2, or 3, as previously
      defined. Type 1 and 2 perforations are predominately caused by hydrophilic and
      stiff wires and do not require pericardial drainage or surgical intervention.
      Type 3 perforations are more often associated with stent and device use and can
      be initially managed by percutaneous methods.

PMID- 19755316
TI  - The how and why of... Chronic Total Occlusions. Part One: How to treat CTOs.

PMID- 19755315
TI  - What is the role for revascularisation in patients being considered for ICD
      therapy?
AB  - Patients being considered for ICD therapy are a heterogeneous group.For the vast
      majority, who have significant left ventricular impairment, it has become common
      practice to assess their coronary artery anatomy as a surrogate for ischaemia
      and/or viability. Such patients are therefore frequently under the care of both
      electrophysiologists and interventionists. The coronary anatomy often raises the
      dilemma about whether such patients should undergo revascularisation. If the
      patients present with angina or in the context of an acute myocardial infarct
      then this decision is clear cut. By contrast, however, a significant proportion
      of them have no history to suggest ongoing ischaemia or of recent MI. In
      conventional practice, therefore, there would be no decisive mandate to offer
      them revascularisation, especially PCI, in the absence of further objective
      evidence of ischaemia or viability. A review of the literature in our paper does
      not resolve this dilemma.Further observational data are required to help guide
      cardiologists as to which of these patients will benefit from revascularisation,
      since in many cases the coronary anatomy is no surrogate for the presence of
      ischaemia or viability.

PMID- 19755317
TI  - The how and why of... Chronic Total Occlusions. Part Two: Why we treat CTOs the
      way we do.

PMID- 19755318
TI  - Contrast enhancement of coronary arteries in cardiac surgery: a new multispectral
      stereoscopic camera technique.
AB  - OBJECTIVE: During open heart surgery, the myocardium usually provides sufficient
      visual contrast with both epicardial veins and arteries. However, visibility of
      coronary arteries may occasionally be impaired due to, e.g., intra-myocardial
      course of coronary arteries, increased epicardial fat, epicardial post-surgical
      adhesions, or pericarditis. Seen within the near infra-red range, coronary
      arteries show higher contrasts in relation to the myocardium than coronary veins.
      Hence, we developed a non-contact stereo-optical camera to selectively enhance
      coronary arteries by combining visible and near infra-red images. In this paper
      we present our first results on porcine and human hearts. MATERIALS AND METHODS:
      Two CMOS-cameras, with apochromatic lenses and dual-band LED-arrays, -captured
      visible colour (visible range, or VIS, 400-780nm) and near infra-red grey-scale
      (near infra-red range, or NIR, 910-920nm) images by sequentially switching
      between LED-array emission bands. Data was recorded by computer and processed off
      line. Arterial NIR contrasts were algorithmically distinguished from shadows and
      specular reflections. Detected arteries were selectively enhanced and back
      projected into the stereoscopic VIS-colour-image using either a 3D-display or
      conventional shutter glasses. RESULTS: Our technique visualised coronary
      vasculature and allowed to identify concealed parts of coronary arteries using
      off-line processing. Raw VIS & NIR images were real-time, processing took < 15s
      after filming. CONCLUSION: The applied principle works, but needs further
      development.

PMID- 19755319
TI  - The Bedside Celution system for isolation of adipose derived regenerative cells.

PMID- 19755320
TI  - 20 years of stenting: a patient's perspective.

PMID- 19755321
TI  - Biodegradable drug eluting stents: invasive and non-invasive imaging.

PMID- 19755324
TI  - Stent selection in patients on oral anticoagulants: can we prevent restenosis and
      avoid bleeding?

PMID- 19755325
TI  - Meta-analytic rage or race for evidence-based interventional cardiology?

PMID- 19755326
TI  - Informed consent in interventional cardiology.

PMID- 19755327
TI  - Correlations between epicardial flow, microvascular reperfusion, infarct size and
      clinical outcomes in patients with anterior versus non-anterior myocardial
      infarction treated with primary or rescue angioplasty: analysis from the EMERALD
      trial.
AB  - AIMS: We compared epicardial and microvascular reperfusion, infarct size, and
      clinical outcomes after primary and rescue PCI with and without GuardWire distal
      protection in patients with LAD vs. non-LAD acute myocardial infarction (AMI). In
      the general AMI population undergoing primary PCI, the use of GuardWire did not
      yield higher reperfusion success, reduced infarct size, or enhanced event-free
      survival. Whether GuardWire is beneficial in patients with AMI in certain
      territories of the coronary circulation is unknown. METHODS AND RESULTS: In the
      EMERALD trial, 501 patients with AMI were randomised to PCI with vs. without
      distal protection. The outcomes were analysed as a function of culprit vessel
      (LAD vs. non-LAD) and the use of GuardWire. Patients with LAD vs. non-LAD
      infarcts had significantly (P< or =0.0001) lower rates of final TIMI flow grade 3
      (85.2% vs. 94.4%), myocardial blush grade 3 (40.1% vs. 67.6%), and complete ST
      segment resolution (35.1% vs. 79.6%). Patients with LAD infarcts also had larger
      infarct size (25.8+/-21.8% vs. 11.3_13.7%, p<0.0001) and a trend towards higher
      rates of 6-month mortality (5.5% vs. 2.1%, p=0.09) and new-onset severe heart
      failure (3.5% vs. 1.1%, p=0.08). Rates of reperfusion were not related to
      GuardWire use in patients with LAD infarcts. In patients with non-LAD infarcts,
      the use of GuardWire was associated with a trend towards better epicardial and
      microvascular reperfusion. CONCLUSIONS: Myocardial infarction in the territory of
      the LAD is associated with worse epicardial and microvascular reperfusion and
      worse 6-month clinical outcomes. Use of the GuardWire showed a trend towards
      better epicardial and microvascular flow in patients with a non-LAD infarct
      related artery.

PMID- 19755328
TI  - Early and late increased bleeding rates after angioplasty and stenting due to
      combined antiplatelet and anticoagulanttherapy.
AB  - AIMS: To assess major bleeding complications in patients after coronary stenting
      who are on dual antiplatelet drugs with or without oral anticoagulants. METHODS
      AND RESULTS: Bleeding complications necessitating hospital admission were
      prospectively recorded during initial hospitalisation and during a complete
      follow-up of three years in 813 consecutive patients undergoing coronary artery
      stenting. All patients were assigned to antiplatelet therapy with aspirin and
      clopidogrel for at least six months and continued aspirin use thereafter. There
      were 25 early bleedings and 26 late hospital admissions for bleeding. Forty-four
      patients (5.4%) were on oral anticoagulants (coumadin) in addition to
      antiplatelet agents. The rate of late severe bleeding was 6.1% per year with, vs.
      0.8% without coumadin (p <0.0001). In multivariate analyses GPIIb/IIIa (OR 3.8
      95%-CI 1.6-8.8, p=0.002), female gender (=R 2.5, 95%CI 1.1-5.8, p=0.04) and age
      (OR 1.44 per decade, 95%CI 0.99-2.08, p=0.05) were independent predictors of
      early bleeding; and LVEF (OR 0.65 per 10% increase, 95%CI 0.48-0.87, p=0.004),
      history of malignancy (OR 5.1, 95%CI 1.5-17.0, p=0.009) and coumadin use (OR
      3.5,95%CI 1.1-11.5, p=0.04) for late bleeding. CONCLUSIONS: For patients on oral
      anticoagulants, drug eluting stents necessitating sustained dual antiplatelet
      therapy should be used with caution. Specific risk factors for bleeding
      complications should guide anticoagulation after PCI.

PMID- 19755329
TI  - Long-term follow-up after drug eluting stent implantation in left main
      trifurcations.
AB  - AIMS: Trifurcation lesions, which are mostly observed in distal left main (LM),
      represent a technical challenge for interventional cardiologists. We sought to
      determine the feasibility and long-term clinical outcome of drug eluting stent
      (DES) implantation in patients with LM coronary trifurcation lesions. METHODS AND
      RESULTS: All patients with clinically significant de novo LM trifurcation
      lesions, who refused coronary artery bypass surgery and were considered eligible
      for percutaneous coronary intervention (PCI), were consecutively enrolled in this
      study from November 2005 to February 2007. Eleven patients (65+/-9 years, 91%
      men) met all the inclusion criteria and underwent LM trifurcation stenting with
      DES. Angiographic success was 100%. Clinical follow-up in all patients and
      angiographic follow-up in 91% of patients was available at 32+/-7 and 8+/-2
      months, respectively. The primary endpoint, defined as the composite of cardiac
      death or acute myocardial infarction, occurred in one patient (9%). No cases of
      stent thrombosis were recorded. Three patients (27%), experienced a clinically
      driven target lesion revascularisation (TLR). CONCLUSIONS: PCI with DES
      implantation in patients with LM trifurcation seems feasible and safe, with
      acceptable TLR rates. Large scale multicentre registries are warranted to
      reliably address clinical outcome of this subset of patients.

PMID- 19755330
TI  - Aorto-iliac angiography as a screening tool in selecting patients for
      transfemoral aortic valve implantation with the Edwards SAPIEN bioprosthesis.
AB  - AIMS: Transcatheter aortic valve replacement (TAVR) is a promising therapeutic
      option for patients with severe aortic stenosis (AS) considered at too high risk
      for conventional aortic valve replacement. The balloon-expandable Edwards valve
      can be implanted using either the transfemoral or transapical routes, depending
      on arterial ilio-femoral suitability. The aim of the study was to evaluate the
      usefulness of ilio-femoral angiography as an initial screening tool for TAVR
      using the transfemoral approach with the Edwards SAPIEN valve. METHODS AND
      RESULTS: Aortography with bilateral ilio-femoral run-off was assessed in the
      antero-posterior projection. Minimal arterial diameter, vessel tortuosity and
      calcification were assessed. Transfemoral implantation was appropriate when the
      minimal arterial diameter was >7 mm for a 23 mm trans-catheter heart valve (THV)
      and >8 mm for a 26 mm THV with limited calcifications and tortuosity. Included
      were 135 patients with severe aortic stenosis undergoing cardiac catheterisation
      before conventional aortic valve replacement or TAVR. Mean femoral artery
      diameter was 7.5+/-1.3 mm and mean iliac artery diameter was 9.3+/-2.3 mm. There
      was no or moderate tortuosity in 72% of them. Calcifications were absent or
      moderate in 83%. At first sight, the transfemoral route was considered
      potentially suitable in 71% of patients for a 23 mm THV and 39% of patients for a
      26 mm TAVI. CONCLUSIONS: In the course of haemodynamic and angiographic
      evaluation of patients with severe symptomatic aortic stenosis, angiography of
      the ilio-femoral access can be used as a first screening modality to determine
      potential candidacy for a transfemoral TAVR using a balloon expandable THV.

PMID- 19755331
TI  - The recurrence of iatrogenic femoral artery pseudoaneurysm after occlusion by
      ultrasound guided percutaneous thrombin injection.
AB  - AIMS: To evaluate efficacy of percutaneous ultrasound-guided thrombin injection
      (UGTI) of iatrogenic femoral artery pseudoaneurysm (PSA) and to identify the risk
      factors associated with PSA recurrence. METHODS AND RESULTS: We treated 140
      patients aged 76 years (range 49-83) presented with femoral artery PSA after
      cardiac catheterisation by percutaneous UGTI (500 IU/ml solution of activated
      human thrombin). Factors associated with the recurrence of PSA were analysed. One
      hundred nineteen patients were successfully treated by one injection of thrombin
      (immediate success rate 85%). In 19 patients (13.6%), short local compression
      following injection was needed for complete occlusion (overall success rate
      98.6%, 138/140). In one case, progression of PSA required conversion to surgery
      (0.7%). In one patient with pre-existing stenosis of superficial femoral artery,
      acute limb ischaemia developed after UGTI (0.7%). The recurrence of PSA in 30
      days follow-up (10 patients, 7%) was associated with obesity (BMI>30, OR=1.39,
      95% CI 1.09-1.78, p<0.05), and with extensive combination of anti-aggregation and
      anti-coagulation therapy (OR=2.11, 95% CI 1.23-3.62, p<0.0001) as revealed by
      both univariate and multivariate analysis. CONCLUSIONS: The UGTI is a safe and
      effective treatment of iatrogenic femoral artery PSA. Recurrence is low and
      associated with obesity and extensive use of combined anti-aggregation and anti
      coagulation therapy.

PMID- 19755332
TI  - Comparison of the very long term (>1 year) outcomes of drug-eluting stents for
      the treatment of bare-metal and drug-eluting stent restenosis.
AB  - AIMS: Drug-eluting stents (DES) have become the first choice to treat BMS
      restenosis (ISR), replacing brachytherapy and all other available percutaneous
      approaches. Although markedly reduced, DES ISR still occurs and has been
      frequently treated with another DES, despite the lack of robust data supporting
      the safety and efficacy of this approach. We sought to compare the long term
      clinical outcomes of patients with BMS and DES ISR treated with another DES
      deployment. METHODS AND RESULTS: Between May 2002 and January 2008 a total of 158
      patients with BMS restenosis and 58 patients with DES restenosis were treated
      with a DES and enrolled in this registry. Primary endpoint included the
      cumulative occurrence of major adverse cardiac events (MACE=cardiac death,
      myocardial infarction and target-vessel revascularisation) and stent thrombosis.
      Baseline clinical aspects did not significantly differ between the groups. There
      was a trend toward a higher incidence of DM in the DES cohort (36.1% vs. 32.9%,
      p=0.1). Mean time between first procedure and restenosis was significant longer
      in the DES population (178+/-61 days vs. 140+/-38 days, p=0.02). At the end of
      the follow-up period, 92.6% of the patients with BMS-ISR and 86.3% of those with
      DES-ISR were free of MACE (p<0.001). Patients with DES ISR had significant more
      recurrence of ISR but equivalent rates of cardiac death, MI and stent thrombosis.
      CONCLUSIONS: Percutaneous treatment of BMS or DES ISR with the implant of a DES
      represents a simple and safe approach with sustained long term results. However,
      the relatively high rate of ISR recurrence among patients with prior DES ISR
      demand the developing of more effective strategies for that subset of
      individuals.

PMID- 19755333
TI  - Long-term clinical outcome of alternative treatment strategies for drug-eluting
      stents restenosis.
AB  - AIMS: Due to the widespread use of drug-eluting stents (DES), in-DES restenosis
      is increasing. The aim of this study is to evaluate the clinical outcome of
      patients undergoing repeat percutaneous coronary intervention (PCI) for DES
      restenosis. METHODS AND RESULTS: One hundred patients with 108 restenotic lesions
      using DES were consecutively enrolled in a single-arm 2-centre registry. The
      repeat-PCI was performed either with balloon angioplasty (POBA) or with DES
      implantation (homo-stent or hetero-stent). Major adverse cardiac events (MACE)
      occurrence was assessed long-term. Of the 108 DES restenotic lesions, 34 were
      treated with balloon angioplasty, 43 with homo-stent and 31 with hetero-stent
      implantation. Of the patients, 37% had diabetes mellitus, while 30% peripheral or
      carotid artery disease. Over a mean follow-up of 16.0+/-6.0 months, the rates of
      death, myocardial infarction (MI), and ischaemic driven target lesion
      revascularisation (IDTLR) in hetero-stent, homo-stent and POBA groups were
      respectively 0% vs. 5% vs. 3% (p=NS), 2% vs. 5% vs. 0% (p=NS) and 17% vs. 23% vs.
      25% (p=NS). When comparing patients treated with POBA to those receiving hetero
      /homo-DES, no significant difference in terms of IDTLR (25% vs. 20%; p=NS), MI
      (0% vs. 4%; p=NS) and overall MACE (25% vs. 23%, p=NS) appeared. The presence of
      previous MI (OR 0.05; 95% CI 0.01-0.3), first DES implanted for BMS restenosis
      (OR 0.16; 95% CI 0.02-0.99) and peripheral or carotid disease (OR 0.09; 95% CI
      0.01-0.67) were negative independent predictors of freedom from IDTLR.
      CONCLUSIONS: Repeat balloon angioplasty for DES restenosis showed similar
      clinical outcome compared to re-DES (homo- or hetero-) implantation and could be
      considered as first treatment strategy in this setting.

PMID- 19755334
TI  - Impact of drug eluting stents on the clinical practice of revascularisation of
      coronary artery disease.
AB  - AIMS: Drug-eluting stents (DES) have shown to reduce restenosis rates in all
      lesional subsets. This has expanded the application of percutaneous intervention
      (PCI). In this study we address the impact of the high DES penetration on the
      management of patients referred for coronary angiography. METHODS AND RESULTS: We
      have studied the cohorts of patients referred for coronary angiography in 2000
      2001 prior to DES availability, and in 2005-2006 with a 73% DES implementation.
      In 2000-1 of 2,458 coronary angiographic studies, 84% had significant lesions
      (>50%), 56% had PCI, 8.8% had CABG and in 443 (18%) with significant lesions no
      revascularisation was attempted. In 2005-6 out of 2,600 angiographies, 84% had
      significant lesions, 64% had PCI, 6% had CABG and in 312 (12%) with significant
      lesions no revascularisation was done. The increase in PCI, the reduction in CABG
      and the decrease in non-revascularised diseased cases were all significant
      (p<0,001). The PCI and CABG groups in 2005-6 compared to 2000-1 had a more
      complex lesion profile with, however, less in-stent restenotic lesions treated
      (10% vs 4.2%; p<0.001). CONCLUSIONS: The wide clinical introduction of DES was
      associated with a significant increase in patients undergoing any kind of
      revascularisation, increasing the PCI volume to the detriment of CABG activity.
      Patients with PCI in 2006 had more complex lesions treated, whereas restenosis
      was less frequent.

PMID- 19755335
TI  - Assisted circulation using the Tandemhear , percutaneous transseptal left
      ventricular assist device, during percutaneous aortic valve implantation: the
      Rotterdam experience.
AB  - AIMS: The morbidity and mortality of surgical aortic valve replacement are
      increased in elderly patients with multiple high risk comorbid conditions.
      Percutaneous prosthetic aortic valve replacement (PAVR) via the femoral arterial
      approach is feasible in selected patients, who are poor operative candidates,
      with satisfactory short term outcomes. It is conceivable that patients with poor
      LV function may benefit from periprocedural cardio-circulatory support. We
      evaluated the short-term safety and efficacy of using the TandemHeart PTVA System
      (p-LVAD) to deliver extracorporeal circulatory support in patients undergoing
      PAVR. METHODS AND RESULTS: Between April 2006 and May 2007 the TandemHeart was
      used in 10 patients (age: range 64-85, median 80) undergoing elective PAVR using
      the CoreValve Revalving System. The median (range) time for implementation of
      circulatory support was 32 (22-40) minutes. A pump flow up to 4.6 L/min was
      achieved. Systemic haemodynamics were maintained in all but one patient. The
      median (range) systemic arterial pressure (MBP) was 77 (67-89) mmHg at baseline
      and 76 (61-91) mmHg after pump functioning. A major systolic blood pressure drop
      (systolic blood pressure < 70 mmHg, pulse pressure < 10 mmHg, occurred in one
      patient due to PAVR related pericardial tamponade. Median (range) duration of
      support was 64 (60-93) minutes. Successful weaning was achieved in all patients.
      There was one in hospital death. Survival at 12 months was 90%, at 15 months 70%.
      Vascular access site complications were seen in two patients. One patient
      suffered a mild to moderate access site bleeding, one a local wound infection.
      There was no technical device failure. CONCLUSIONS: The TandemHeart-PTVA may
      provide a valuable safeguard during high risk PAVR procedures and enables precise
      delivery of the CoreValve prosthesis. The rate of device related cardiac and
      vascular complications was acceptable.

PMID- 19755336
TI  - A novel strategy for managing clopidogrel-induced adverse skin reactions.
AB  - AIMS: We conducted a prospective observational study using a course of steroids
      and antihistamines to treat a cohort of patients who developed skin reactions to
      clopidogrel, to assess whether dual antiplatelet therapy could be continued in an
      outpatient setting. METHODS AND RESULTS: This study included 2,701 patients who
      underwent percutaneous coronary intervention (PCI) at our centre over a 23 month
      period. Patients with skin reactions to clopidogrel were identified and then
      commenced on five days oral prednisolone (30 mg/od) and chlorpheniramine (4
      mg/tds) for seven days. A subsequent telephone survey was performed to evaluate a
      number of variables. The probability of the adverse reaction being secondary to
      clopidogrel was assessed using the Naranjo adverse drug reaction probability
      scale. Twenty (0.7%) patients were identified who developed adverse skin
      reactions to clopidogrel. There was complete resolution seen in the majority
      (89%) of patients within an average of 3.2 days following treatment. One patient
      had partial resolution, and one had no response to treatment, but both were able
      to continue clopidogrel. CONCLUSIONS: We propose a novel, safe and effective way
      of managing clopidogrel-induced skin reactions using a short course of
      prednisolone and chlorpheniramine, without stopping or substituting clopidogrel.

PMID- 19755337
TI  - Bifurcation stenting with drug-eluting stents: a systematic review and meta
      analysis of randomised trials.
AB  - AIMS: We sought to determine if outcomes differ between provisional (elective
      side branch stenting) compared to a routine two-stent strategy (mandatory side
      branch stenting) for the treatment of bifurcation stenoses of the coronary
      arteries using drug-eluting stents. METHODS AND RESULTS: We searched Medline,
      EMBASE, and the Cochrane library from January 2000 to February 2009 for studies
      comparing the provisional and two-stent strategies. Six randomised controlled
      trials, including 1,641 patients, were identified. The relative risk (95%
      confidence interval) for death, MI, target lesion revascularisation, and stent
      thrombosis within 1-year of the index procedure for a provisional vs. two-stent
      strategy were 1.12 (0.42-3.02), 0.57 (0.37-0.87), 0.91 (0.61-1.35), and 0.56
      (0.23-1.35), respectively. By quantitative coronary angiography, there was no
      difference in the difference in means (95% CI) between the provisional and two
      stent strategies for percent diameter stenosis (95% CI) in the main vessel or
      side branch, -1.08 (-2.91 to 0.74) and 1.30 (-3.35 to 5.96), respectively.
      CONCLUSION: While death, stent thrombosis, and restenosis were similar between
      the treatment groups, MI was more common with the two-stent strategy. Thus,
      compared to a routine two-stent strategy, provisional stenting yields similar
      efficacy with superior safety and lower costs.

PMID- 19755338
TI  - Directional coronary atherectomy: a time for reflection. Should we let it go?
AB  - A series of interventional tools have emerged since the advent of percutaneous
      coronary angioplasty. Several are fundamental and used routinely, while others
      less favourable have fallen short of mainstream therapy and/or have settled as a
      niche device. We present an overview of the evolution of directional coronary
      atherectomy (DCA), a unique device that was originally conceived in 1984 to solve
      the limitations of balloon angioplasty. Unfortunately, we have witnessed its use
      fall significantly out of favour due to premature and controversial study
      results. In many interventional laboratories DCA is no longer available. However,
      we strongly feel that allowing DCA to join the list of extinct interventional
      tools would be very unfortunate. We, herein, present a series of complex
      percutaneous coronary procedures to illustrate the convenience of DCA use as a
      lesion-specific niche device. Finally, DCA offers a valuable distinct clinical
      research function as it allows for in vivo pathological coronary tissue
      examination. In conclusion, we plead for its continued production and use as an
      interventional niche device for the wellbeing of our patients.

PMID- 19755339
TI  - The use of drug-eluting stents in ST-elevation myocardial infarction.
AB  - Drug-eluting stents (DES) dramatically lower rates of restenosis in patients
      undergoing percutaneous coronary interventions. However, their use has extended
      beyond the initial approved indications into off-label scenarios such as ST
      elevation myocardial infarction (STEMI). Multiple retrospective case series and
      10 prospective randomised controlled trials have been published on the use of DES
      in STEMI patients, and these generally show reduced rates of target vessel
      revascularisation with a neutral effect on mortality. Three meta-analyses show
      similar findings with the composite endpoint of death, recurrent myocardial
      infarction, or re-intervention significantly lower in the DES group, although
      this was largely driven by a decrease in target vessel revascularisation. These
      studies also demonstrate that DES use in the setting of STEMI is not associated
      with increased risk of stent thrombosis compared to bare metal stents. In
      summary, current data support the efficacy of DES in reducing restenosis and re
      intervention in patients who present with STEMI. From a safety standpoint, the
      use of DES in STEMI does not increase the risk of stent thrombosis, and there is
      no difference in overall mortality. The use of DES in STEMI patients should be
      individualised on a case-by-case basis given the importance of compliance with
      dual antiplatelet therapy.

PMID- 19755340
TI  - The SCAAR-scare in perspective.

PMID- 19755341
TI  - Scanning electron microscopic assessment of the biodegradable coating on expanded
      biolimus-eluting stents.
AB  - AIMS: Biodegradable coatings on drug-eluting stents (DES) may help to avoid
      adverse long-term effects of DES such as late/very late stent thrombosis which is
      partly attributed to durable polymers. As the post-expansion morphology of
      biodegradable coatings is greatly unknown, we investigated the polylactic acid
      coating on biolimus-eluting BioMatrix stents. METHODS AND RESULTS: Scanning
      electron microscopy (SEM) was used to carefully examine five 3.5mm stents
      following expansion at 6-14atm (maximum 7% overstretch). SEM examination
      demonstrated only mild cracks of the coating after stent expansion at 6 atm. An
      increase in expansion pressure, associated with mild stent overstretch, resulted
      in more severe cracks. Lifting of the coating together with few sites of partial
      detachment of fragments was noticed after stent expansion in water at 14atm;
      these irregularities further increased after aggressive oversized partial
      postdilatation with a 5.0mm non-compliant balloon with additional secondary
      cracks. CONCLUSIONS: SEM assessment suggests a relatively low elasticity of the
      biodegradable coating on BioMatrix stents. At nominal pressure, stents showed
      predominantly mild cracks of the coating, while cracks increased after slight
      overstretch. Aggressive overexpansion of the stent, such as sometimes required in
      left main bifurcation stenting, worsened cracks and led to some detachment of
      fragments of the coating in vitro.

PMID- 19755342
TI  - Percutaneous coronary intervention of ostial lesions.

PMID- 19755343
TI  - Virtual 3 Fr PCI system for complex percutaneous coronary intervention.

PMID- 19755346
TI  - Randomized trials and technology assessment.

PMID- 19755348
TI  - Systematic review: charged-particle radiation therapy for cancer.
AB  - BACKGROUND: Radiation therapy with charged particles can potentially deliver
      maximum doses while minimizing irradiation of surrounding tissues, and it may be
      more effective or less harmful than other forms of radiation therapy. PURPOSE: To
      review evidence about the benefits and harms of charged-particle radiation
      therapy for patients with cancer. DATA SOURCES: MEDLINE (inception to 11 July
      2009) was searched for publications in English, German, French, Italian, and
      Japanese. Web sites of manufacturers, treatment centers, and professional
      organizations were searched for relevant information. STUDY SELECTION: Four
      reviewers identified studies of any design that described clinical outcomes or
      adverse events in 10 or more patients with cancer treated with charged-particle
      radiation therapy. DATA EXTRACTION: The 4 reviewers extracted study, patient, and
      treatment characteristics; clinical outcomes; and adverse events for
      nonoverlapping sets of articles. A fifth reviewer verified data on comparative
      studies. DATA SYNTHESIS: Currently, 7 centers in the United States have
      facilities for particle (proton)-beam irradiation, and at least 4 are under
      construction, each costing between $100 and $225 million. In 243 eligible
      articles, charged-particle radiation therapy was used alone or in combination
      with other interventions for common (for example, lung, prostate, or breast) or
      uncommon (for example, skull-base tumors or uveal melanomas) types of cancer. Of
      243 articles, 185 were single-group retrospective studies. Eight randomized and 9
      nonrandomized clinical trials compared treatments with or without charged
      particles. No comparative study reported statistically significant or important
      differences in overall or cancer-specific survival or in total serious adverse
      events. LIMITATION: Few studies directly compared treatments with or without
      particle irradiation. CONCLUSION: Evidence on the comparative effectiveness and
      safety of charged-particle radiation therapy in cancer is needed to assess the
      benefits, risks, and costs of treatment alternatives.

PMID- 19755349
TI  - ACP Journal Club. Editorial: Accessing preappraised evidence: fine-tuning the 5S
      model into a 6S model.

PMID- 19755350
TI  - ACP Journal Club. Review: Aspirin reduces vascular events but increases bleeding
      in primary and secondary prevention.

PMID- 19755351
TI  - ACP Journal Club. Review: Aspirin does not reduce CV events but may reduce
      nonfatal stroke in peripheral artery disease.

PMID- 19755352
TI  - ACP Journal Club. Review: Intensive glucose control reduced some CV events but
      did not change mortality in type 2 diabetes.

PMID- 19755353
TI  - ACP Journal Club. Review: Erythropoiesis-stimulating agents increase mortality in
      patients with cancer.

PMID- 19755354
TI  - ACP Journal Club. In patients with atrial fibrillation, adding clopidogrel to
      aspirin reduced major vascular events but increased bleeding.

PMID- 19755355
TI  - ACP Journal Club. Ultrasonography-guided oral anticoagulant therapy reduced
      recurrent venous thromboembolism.

PMID- 19755356
TI  - ACP Journal Club. Rosuvastatin reduced venous thromboembolism in healthy older
      adults with elevated C-reactive protein levels.

PMID- 19755357
TI  - ACP Journal Club. Review: Steroid avoidance or withdrawal does not increase
      mortality or graft loss in kidney transplant patients.

PMID- 19755358
TI  - ACP Journal Club. Review: Low-dose corticosteroids improve outcomes in acute lung
      injury and the acute respiratory distress syndrome.

PMID- 19755359
TI  - Cholinesterase inhibitors were associated with increased risk for syncope and its
      consequences in older persons with dementia.

PMID- 19755360
TI  - A ward-based pharmacist intervention reduced emergency department visits and drug
      related readmissions in elderly patients.

PMID- 19755361
TI  - ACP Journal Club. Review: 3 prediction rules, particularly ABCD, identify ED
      patients who can be discharged with low risk for stroke after TIA.

PMID- 19755362
TI  - Case management for depression by health care assistants in small primary care
      practices: a cluster randomized trial.
AB  - BACKGROUND: Case management by health care assistants in small primary care
      practices provides unclear benefit for improving depression symptoms. OBJECTIVE:
      To determine whether case management provided by health care assistants in small
      primary care practices is more effective than usual care in improving depression
      symptoms and process of care for patients with major depression. DESIGN: Cluster
      randomized, controlled trial. A central automated system generated the
      randomization scheme, which was stratified by urban and rural practices;
      allocation sequence was concealed until groups were assigned. SETTING: 74 small
      primary care practices in Germany from April 2005 to September 2007. PATIENTS:
      626 patients age 18 to 80 years with major depression. INTERVENTION: Structured
      telephone interview to monitor depression symptoms and support for adherence to
      medication, with feedback to the family physician. MEASUREMENTS: Depression
      symptoms at 12 months, as measured by the Patient Health Questionnaire-9 (PHQ-9);
      secondary outcomes were patient assessment of chronic illness care, adherence to
      medication, and quality of life. RESULTS: A total of 310 patients were randomly
      assigned to case management and 316 to usual care. At 12 months, 249 intervention
      recipients and 278 control patients were assessed; 555 patients were included in
      a modified intention-to-treat-analysis (267 intervention recipients vs. 288
      control patients). Compared with control patients, intervention recipients had
      lower mean PHQ-9 values in depression symptoms (-1.41 [95% CI, -2.49 to -0.33]; P
      = 0.014), more favorable assessments of care (3.41 vs. 3.11; P = 0.011), and
      increased treatment adherence (2.70 vs. 2.53; P = 0.042). Quality-of-life scores
      did not differ between groups. LIMITATION: Patients, health care assistants,
      family physicians, and researchers were not blinded to group assignment, and 12
      month follow-up of patients was incomplete. CONCLUSION: Case management provided
      by primary care practice-based health care assistants may reduce depression
      symptoms and improve process of care for patients with major depression more than
      usual care. PRIMARY FUNDING SOURCE: German Ministry of Education and Research.

PMID- 19755363
TI  - Ambulatory care among young adults in the United States.
AB  - BACKGROUND: Young adults are the most likely age group to be uninsured and have
      the highest prevalence of substance abuse, motor vehicle accidents, and sexually
      transmitted diseases, yet little is known about their use of ambulatory care.
      OBJECTIVE: To characterize ambulatory care of young adults. DESIGN: Cross
      sectional data from the National Ambulatory Medical Care Survey and National
      Hospital Ambulatory Medical Care Survey. SETTING: Community and hospital-based
      clinics. PATIENTS: Nonpregnant young adults age 20 to 29 years. MEASUREMENTS:
      Ambulatory care utilization, types of visits, and preventive care. RESULTS:
      Insured young adults had more visits (2.16 [95% CI, 2.14 to 2.19] annual visits
      per capita) than those without insurance (0.59 [CI, 0.54 to 0.67] annual visits
      per capita). Young men utilized ambulatory medical care less than adolescents age
      15 to 19 years or older adults age 30 to 39 years (1.10, 1.65, and 1.73 annual
      visits per capita, respectively) and had lower rates of utilization than young
      women (1.10 vs. 2.31 annual visits per capita). Young black and Hispanic men had
      considerably fewer annual visits per capita (0.75 and 0.65, respectively) than
      did young white men (1.21). Young men had nearly one half the preventive care
      visits compared with male adolescents or older men (0.11, 0.24, and 0.19 annual
      visits per capita, respectively) and less than one quarter the visits compared
      with young women (0.11 vs. 0.48 annual visits per capita). Only 30.6% of visits
      by young adults included any preventive counseling, and few encounters included
      counseling directed toward injury prevention (2.4%), mental health (4.1%), or
      sexually transmitted diseases (2.7%). LIMITATION: School-based clinics were not
      included, and counseling may be underreported. CONCLUSION: Young adults use less
      ambulatory medical care relative to other groups and infrequently receive
      preventive care directed at the greatest threats to their health. Efforts to
      ensure appropriate preventive care are needed. PRIMARY FUNDING SOURCE: None.

PMID- 19755364
TI  - The net value of health care for patients with type 2 diabetes, 1997 to 2005.
AB  - BACKGROUND: The net economic value of increased health care spending remains
      unclear, especially for chronic diseases. OBJECTIVE: To assess the net value of
      health care for patients with type 2 diabetes. DESIGN: Economic analysis of
      observational cohort data. SETTING: Mayo Clinic, Rochester, Minnesota, a not-for
      profit integrated health care delivery system. PATIENTS: 613 patients with type 2
      diabetes. MEASUREMENTS: Changes in inflation-adjusted annual health care spending
      and in health status between 1997 and 2005 (with health status defined as 10-year
      cardiovascular risk), holding age and diabetes duration constant across the
      observation period ("modifiable risk"), and simulated outcomes for all diabetes
      complications based on the UKPDS (United Kingdom Perspective Diabetes Study)
      Outcomes Model. Net value was estimated as the present discounted monetary value
      of improved survival and avoided treatment spending for coronary heart disease
      minus the increase in annual spending per patient. RESULTS: Assuming that 1 life
      year is worth $200,000 and accounting for changes in modifiable cardiovascular
      risk, the net value of changes in health care for patients with type 2 diabetes
      was $10,911 per patient (95% CI, -$8480 to $33,402) between 1997 and 2005, a
      positive dollar value that suggests the value of health care has improved despite
      increased spending. A second approach based on diabetes complications yielded a
      net value of $6931 per patient (CI, -$186,901 to $211,980). LIMITATION: The
      patient population was homogeneous and small, and the wide CIs of the estimates
      are compatible with a decrease as well as an increase in value. CONCLUSION: The
      economic value of improvements in health status for patients with type 2 diabetes
      seems to exceed or equal increases in health care spending, suggesting that those
      increases were worth the extra cost. However, the possibility that society is
      getting less value for its money could not be statistically excluded, and there
      is opportunity to improve the value of diabetes-related health care. PRIMARY
      FUNDING SOURCE: None.

PMID- 19755365
TI  - Meta-analysis: retinal vessel caliber and risk for coronary heart disease.
AB  - BACKGROUND: Retinal vessel caliber may be a novel marker of coronary heart
      disease (CHD) risk. However, the sex-specific effect, magnitude of association,
      and effect independent of traditional CHD disease risk factors remain unclear.
      PURPOSE: To determine the association between retinal vessel caliber and risk for
      CHD. DATA SOURCES: Relevant studies in any language identified through MEDLINE
      (1950 to June 2009) and EMBASE (1950 to June 2009) databases. STUDY SELECTION:
      Studies were included if they examined a general population, measured retinal
      vessel caliber from retinal photographs, and documented CHD risk factors and
      incident CHD events. DATA EXTRACTION: 6 population-based prospective cohort
      studies provided data for individual participant meta-analysis. DATA SYNTHESIS:
      Proportional hazards models, adjusted for traditional CHD risk factors, were
      constructed for retinal vessel caliber and incident CHD in women and men. Among
      22,159 participants who were free of CHD and followed for 5 to 14 years, 2219
      (10.0%) incident CHD events occurred. Retinal vessel caliber changes (wider
      venules and narrower arterioles) were each associated with an increased risk for
      CHD in women (pooled multivariable-adjusted hazard ratios, 1.16 [95% CI, 1.06 to
      1.26] per 20-microm increase in venular caliber and 1.17 [CI, 1.07 to 1.28] per
      20-microm decrease in arteriolar caliber) but not in men (1.02 [CI, 0.94 to 1.10]
      per 20-microm increase in venular caliber and 1.02 [CI, 0.95 to 1.10] per 20
      microm decrease in arteriolar caliber). Women without hypertension or diabetes
      had higher hazard ratios. LIMITATION: Error in the measurement of retinal vessel
      caliber and Framingham variables was not taken into account. CONCLUSION: Retinal
      vessel caliber changes were independently associated with an increased risk for
      CHD events in women.

PMID- 19755366
TI  - Method for establishing authorship in a multicenter clinical trial.
AB  - With the emergence of large multicenter trials over the past 20 years, the
      numbers of investigators involved and publications resulting from each study have
      grown exponentially. An efficient, fair, and effective way to establish
      authorship on study-related manuscripts could diminish conflict among the
      investigators and help ensure robust and timely dissemination of study results.
      This article describes a process developed by the investigators in the HF-ACTION
      (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training)
      trial (ClinicalTrials.gov registration number: NCT00047437) to establish
      authorship of the manuscripts describing the baseline characteristics, study
      design, and trial outcomes in an equitable and transparent manner based on
      objective, quantifiable contributions to the study as a whole. The HF-ACTION
      investigators developed a scoring system that assigned points to investigators by
      using the criteria established for enrollment, adherence to the exercise program,
      data completion, committee service, and other trial efforts. The scoring system
      has been successfully implemented for baseline manuscripts and has allowed many
      investigators to participate in the HF-ACTION publication process.

PMID- 19755367
TI  - Last-resort options for palliative sedation.
AB  - Despite receiving state-of-the-art palliative care, some patients still
      experience severe suffering toward the end of life. Palliative sedation is a
      potential way to respond to such suffering, but access is uneven and
      unpredictable, in part because of confusion about different kinds of sedation.
      Proportionate palliative sedation (PPS) uses the minimum amount of sedation
      necessary to relieve refractory physical symptoms at the very end of life. To
      relieve suffering may require progressive increases in sedation, sometimes to the
      point of unconsciousness, but consciousness is maintained if possible. Palliative
      sedation with the intended end point of unconsciousness (PSU) is a more
      controversial practice that may be considered for much fewer refractory cases.
      There is more ethical consensus about PPS than PSU. In this article, the authors
      explore the clinical, ethical, and legal issues associated with these practices.
      They recommend that palliative care and hospice programs develop clear policies
      about PPS and PSU, including mechanisms for training and ensuring competency for
      clinicians, and approaching situations where individuals or institutions may
      conscientiously object.

PMID- 19755368
TI  - Progress on primary care management of depression.

PMID- 19755369
TI  - A role in transition.

PMID- 19755370
TI  - Would a nursing home physician specialty resolve the workforce crisis in long
      term care?

PMID- 19755371
TI  - Would a nursing home physician specialty resolve the workforce crisis in long
      term care?

PMID- 19755372
TI  - Would a nursing home physician specialty resolve the workforce crisis in long
      term care?

PMID- 19755373
TI  - Would a nursing home physician specialty resolve the workforce crisis in long
      term care?

PMID- 19755374
TI  - Would a nursing home physician specialty resolve the workforce crisis in long
      term care?

PMID- 19755375
TI  - Vitamin K to correct overanticoagulation.

PMID- 19755376
TI  - Vitamin K to correct overanticoagulation.

PMID- 19755377
TI  - Vitamin K to correct overanticoagulation.

PMID- 19755378
TI  - Vitamin K to correct overanticoagulation.

PMID- 19755379
TI  - Vitamin K to correct overanticoagulation.

PMID- 19755380
TI  - Students of medicine: broadening their studies.

PMID- 19755381
TI  - Expression of the familial Mediterranean fever gene is regulated by nonsense
      mediated decay.
AB  - Mutations in the MEditerranean FeVer (MEFV) gene are responsible for familial
      Mediterranean fever (FMF), a recessively inherited auto-inflammatory disease.
      Cases of dominant inheritance and phenotype-genotype heterogeneity have been
      reported; however, the underlying molecular mechanism is not currently
      understood. The FMF protein named pyrin or marenostrin (P/M) is thought to be
      involved in regulating innate immunity but its function remains subject to
      controversy. Recent studies postulate that a defect in MEFV expression regulation
      may play a role in FMF physiopathology. Our group, along with others, has
      identified several alternatively spliced MEFV transcripts in leukocytes. Since
      alternative splicing and nonsense-mediated decay (NMD) pathways are usually
      coupled in the post-transcriptional regulation of gene expression, we
      hypothesized that NMD could contribute to the regulation of the MEFV gene. To
      address this issue, we examined the effect of indirect and direct inhibition of
      NMD on expression of the MEFV transcripts in THP1, monocyte and neutrophil cells.
      We showed that MEFV is the first auto-inflammatory gene regulated by NMD in both
      a cell- and transcript-specific manner. These results and preliminary western
      blot analyses suggest the possible translation of alternatively spliced MEFV
      transcripts into several P/M variants according to cell type and inflammatory
      state. Our results introduce the novel hypothesis that variation of NMD
      efficiency could play an important role in FMF physiopathology as a potent
      phenotypic modifier.

PMID- 19755382
TI  - EKV mutant connexin 31 associated cell death is mediated by ER stress.
AB  - The epidermis expresses a number of connexin (Cx) proteins that are implicated in
      gap junction-mediated cell communication. Distinct dominantly inherited mutations
      in Cx31 cause the skin disease erythrokeratoderma variabilis (EKV) and hearing
      loss with or without neuropathy. Functional studies reveal tissue-specific
      effects of these Cx31 disease-associated mutations. The Cx31 mutants (R42P)Cx31,
      (C86S)Cx31 and (G12D)Cx31 are associated with EKV and the mutant (66delD)Cx31
      with peripheral neuropathy and hearing loss, however the mechanisms of
      pathogenesis remain to be elucidated. Expression of (R42P)Cx31, (C86S)Cx31 and
      (G12D)Cx31 in vitro, but not (WT)Cx31 or (66delD)Cx31, cause elevated levels of
      cell-type specific cell death. Previous studies suggest that Cx-associated cell
      death may be related to abnormal 'leaky' hemichannels but we produced direct
      evidence against that being the major mechanism. Additionally, our
      immunocytochemistry showed upregulation of components of the unfolded protein
      response (UPR) in cells expressing the EKV-associated Cx31 mutants but not
      (WT)Cx31 or (66delD)Cx31. We conclude that the endoplasmic reticulum (ER) stress
      leading to the UPR is the main mechanism of mutant Cx31-associated cell death.
      These results indicate that, in vivo, ER stress may lead to abnormal keratinocyte
      differentiation and hyperproliferation in EKV patient skin.

PMID- 19755383
TI  - Multilocus methylation analysis in a large cohort of 11p15-related foetal growth
      disorders (Russell Silver and Beckwith Wiedemann syndromes) reveals simultaneous
      loss of methylation at paternal and maternal imprinted loci.
AB  - Genomic imprinting plays an important role in mammalian development. Loss of
      imprinting (LOI) through loss (LOM) or gain (GOM) of methylation is involved in
      many human disorders and cancers. The imprinted 11p15 region is crucial for the
      control of foetal growth and LOI at this locus is implicated in two clinically
      opposite disorders: Beckwith Wiedemann syndrome (BWS) with foetal overgrowth
      associated with an enhanced tumour risk and Russell-Silver syndrome (RSS) with
      intrauterine and postnatal growth restriction. So far, only a few studies have
      assessed multilocus LOM in human imprinting diseases. To investigate multilocus
      LOI syndrome, we studied the methylation status of five maternally and two
      paternally methylated loci in a large series (n = 167) of patients with 11p15
      related foetal growth disorders. We found that 9.5% of RSS and 24% of BWS
      patients showed multilocus LOM at regions other than ICR1 and ICR2 11p15,
      respectively. Moreover, over two third of multilocus LOM RSS patients also had
      LOM at a second paternally methylated locus, DLK1/GTL2 IG-DMR. No additional
      clinical features due to LOM of other loci were found suggesting an (epi)dominant
      effect of the 11p15 LOM on the clinical phenotype for this series of patients.
      Surprisingly, four patients displayed LOM at both ICR1 and ICR2 11p15. Three of
      them had a RSS and one a BWS phenotype. Our results show for the first time that
      multilocus LOM can also concern RSS patients. Moreover, LOM can involve both
      paternally and maternally methylated loci in the same patient.

PMID- 19755384
TI  - Nephrocystin-1 and nephrocystin-4 are required for epithelial morphogenesis and
      associate with PALS1/PATJ and Par6.
AB  - Nephronophthisis (NPH) is an autosomal recessive disorder characterized by renal
      fibrosis, tubular basement membrane disruption and corticomedullary cyst
      formation leading to end-stage renal failure. The disease is caused by mutations
      in NPHP1-9 genes, which encode the nephrocystins, proteins localized to cell-cell
      junctions and centrosome/primary cilia. Here, we show that nephrocystin mRNA
      expression is dramatically increased during cell polarization, and shRNA-mediated
      knockdown of either NPHP1 or NPHP4 in MDCK cells resulted in delayed tight
      junction (TJ) formation, abnormal cilia formation and disorganized multi-lumen
      structures when grown in a three-dimensional collagen matrix. Some of these
      phenotypes are similar to those reported for cells depleted of the TJ proteins
      PALS1 or Par3, and interestingly, we demonstrate a physical interaction between
      these nephrocystins and PALS1 as well as their partners PATJ and Par6 and show
      their partial co-localization in human renal tubules. Taken together, these
      results demonstrate that the nephrocystins play an essential role in epithelial
      cell organization, suggesting a plausible mechanism by which the in vivo
      histopathologic features of NPH might develop.

PMID- 19755385
TI  - On Trk--the TrkB signal transduction pathway is an increasingly important target
      in cancer biology.
AB  - In the beginning, Trk was an oncogene. Yet Neurotrophin-Trk signaling came to
      preeminence in the field of neurobiology. Now it is appreciated that Trks
      regulate important processes in nonneuronal cells and, in addition to their
      impact on tumors of neural origin, may contribute to the pathogenesis of
      carcinomas, myelomas, and prostate and lymphoid tumors. Although mutations and
      rearrangements of Trk are seen only sporadically in human cancers, such as
      medullary thyroid carcinoma, a number of recent studies indicate that expression
      of TrkB contributes to tumor pathology. In neuroblastoma, TrkA expression marks
      good prognosis which TrkB and Brain-derived neurotrophic factor (BDNF) expression
      marks poor prognosis. Activation of the BDNF/TrkB signal transduction pathway
      also stimulates tumor cell survival and angiogenesis and contributes to
      resistance to cytotoxic drugs and anoikis, enabling cells to acquire many of the
      characteristic features required for tumorigenesis. Small molecule inhibitors,
      such as Cephalon's CEP-701, are in phase 1 and 2 clinical trials, and a series of
      AstraZeneca Trk inhibitors are poised to enter the clinic. As monotherapy,
      inhibitors may be effective only in tumors with activating Trk mutations.
      Important clinical follow-up will be the assessment of Trk inhibitors in
      combination with standard chemo- or radiotherapy or other signal transduction
      pathway inhibitors.

PMID- 19755386
TI  - Src tyrosine kinase regulates adhesion and chemotaxis in Waldenstrom
      macroglobulinemia.
AB  - PURPOSE: Waldenstrom macroglobulinemia is a lymphoplasmacytic lymphoma
      characterized by widespread involvement of the bone marrow. Despite different
      options of therapy, Waldenstrom macroglobulinemia is still incurable. Src
      tyrosine kinase has been shown to play a central role in the regulation of a
      variety of biological processes, such as cell proliferation, migration, adhesion,
      and survival in solid tumors. We sought to determine whether the protein tyrosine
      kinase Src regulates adhesion, migration, and survival in Waldenstrom
      macroglobulinemia. EXPERIMENTAL DESIGN: We tested the expression of Src tyrosine
      kinase in Waldenstrom macroglobulinemia and normal cells, and the effect of the
      specific Src inhibitor AZD0530 on the adhesion, migration, cell cycle, and
      survival of a Waldenstrom macroglobulinemia cell line and patient samples.
      Moreover, we tested the effect of AZD0530 on cytoskeletal and cell cycle
      signaling in Waldenstrom macroglobulinemia. RESULTS: We show that Src is
      overexpressed in Waldenstrom macroglobulinemia cells compared with control B
      cells, and that the use of the Src inhibitor AZD0530 led to significant
      inhibition of adhesion, migration, and cytoskeletal signaling induced by SDF1.
      Moreover, inhibition of Src activity induced G(1) cell cycle arrest; however, it
      had minimal effect on survival of Waldenstrom macroglobulinemia cells, and no
      significant effect on survival of normal cells. CONCLUSIONS: Taken together,
      these results delineate the role of Src kinase activity in Waldenstrom
      macroglobulinemia and provide the framework for future clinical trials using Src
      inhibitors in combination with other drugs to improve the outcome of patients
      with Waldenstrom macroglobulinemia.

PMID- 19755387
TI  - IDH1 mutations as molecular signature and predictive factor of secondary
      glioblastomas.
AB  - PURPOSE: To establish the frequency of IDH1 mutations in glioblastomas at a
      population level, and to assess whether they allow reliable discrimination
      between primary (de novo) glioblastomas and secondary glioblastomas that
      progressed from low-grade or anaplastic astrocytoma. EXPERIMENTAL DESIGN: We
      screened glioblastomas from a population-based study for IDH1 mutations and
      correlated them with clinical data and other genetic alterations. RESULTS: IDH1
      mutations were detected in 36 of 407 glioblastomas (8.8%). Glioblastoma patients
      with IDH1 mutations were younger (mean, 47.9 years) than those with EGFR
      amplification (60.9 years) and were associated with significantly longer survival
      (mean, 27.1 versus 11.3 months; P < 0.0001). IDH1 mutations were frequent in
      glioblastomas diagnosed as secondary (22 of 30; 73%), but rare in primary
      glioblastomas (14 of 377; 3.7%: P < 0.0001). IDH1 mutations as genetic marker of
      secondary glioblastoma corresponded to the respective clinical diagnosis in 95%
      of cases. Glioblastomas with IDH1 mutation diagnosed as primary had clinical and
      genetic profiles similar to those of secondary glioblastomas, suggesting that
      they may have rapidly progressed from a less malignant precursor lesion that
      escaped clinical diagnosis and were thus misclassified as primary. Conversely,
      glioblastomas without IDH1 mutations clinically diagnosed as secondary typically
      developed from anaplastic rather than low-grade gliomas, suggesting that at least
      some were actually primary glioblastomas, that may have been misclassified,
      possibly due to histologic sampling error. CONCLUSION: IDH1 mutations are a
      strong predictor of a more favorable prognosis and a highly selective molecular
      marker of secondary glioblastomas that complements clinical criteria for
      distinguishing them from primary glioblastomas.

PMID- 19755388
TI  - Down-regulation of ZIP4 by RNA interference inhibits pancreatic cancer growth and
      increases the survival of nude mice with pancreatic cancer xenografts.
AB  - PURPOSE: Zinc levels have been correlated with cancer risk, although the role of
      zinc and zinc transporters in cancer progression is largely unknown. We recently
      found that a zinc transporter, ZIP4, is overexpressed in pancreatic cancer. In
      this study, we further deciphered the role that ZIP4 plays in a pancreatic cancer
      mouse model by silencing ZIP4. EXPERIMENTAL DESIGN: ZIP4 stable silencing was
      established in pancreatic cancer cell lines ASPC-1 (ASPC-shZIP4) and BxPC-3 (BxPC
      shZIP4) by short hairpin RNA using retrovirus vectors. The stable cells were
      characterized in vitro and in vivo using a nude mouse xenograft model. RESULTS:
      Silencing of ZIP4 was associated with decreased cell proliferation, migration,
      and invasion. Both ASPC-shZIP4 and BxPC-shZIP4 cells showed a significant
      reduction in tumor volume and weight in the s.c. model, and decreased primary
      tumor weight in the orthotopic model compared with the vector control cells (ASPC
      shV and BxPC-shV). Silencing of ZIP4 also caused reduced incidence of tumor
      metastasis in the mice and downsized the tumor grade. More importantly, silencing
      of ZIP4 significantly increased the survival rate of nude mice with orthotopic
      xenografts (P = 0.005). All ASPC-shZIP4-injected mice (100%) remained alive up to
      32 days after tumor implantation, whereas only 30% of the ASPC-shV mice were
      alive at the same time point. CyclinD1 expression was decreased in the ASPC
      shZIP4 xenografts. CONCLUSIONS: These results identify a previously
      uncharacterized role of ZIP4 in pancreatic cancer progression, and indicate that
      knocking down ZIP4 by short hairpin RNA might be a novel treatment strategy for
      pancreatic cancers with ZIP4 overexpression.

PMID- 19755389
TI  - A phase I pharmacokinetic and biological correlative study of IMP321, a novel MHC
      class II agonist, in patients with advanced renal cell carcinoma.
AB  - PURPOSE: To evaluate the safety, tolerability, pharmacokinetics, and
      pharmacodynamics of IMP321, a recombinant soluble LAG-3Ig fusion protein which
      agonizes MHC class II-driven dendritic cell activation. EXPERIMENTAL DESIGN:
      Patients with advanced renal cell carcinoma were treated with escalating doses of
      IMP321 s.c. Blood samples were assayed to determine plasma pharmacokinetic
      parameters, detect human anti-IMP321 antibody formation, and determine long-lived
      CD8 T cell responses. RESULTS: Twenty-one advanced renal cell carcinoma patients
      received 119 injections of IMP321 at doses ranging from 0.050 to 30 mg/injection
      s.c. biweekly for 6 injections. No clinically significant adverse events were
      observed. Good systemic exposure to the product was obtained following s.c.
      injections of doses above 6 mg. IMP321 induced both sustained CD8 T-cell
      activation and an increase in the percentage of long-lived effector-memory CD8 T
      cells in all patients at doses above 6 mg. Tumor growth was reduced and
      progression-free survival was better in those patients receiving higher doses (>6
      mg) of IMP321: 7 of 8 evaluable patients treated at the higher doses experienced
      stable disease at 3 months compared with only 3 of 11 in the lower dose group (P
      = 0.015). CONCLUSION: The absence of toxicity and the demonstration of activity
      at doses above 6 mg warrant further disease-directed studies of IMP321 in
      combined regimens (e.g., chemoimmunotherapy).

PMID- 19755390
TI  - Lung cancer in never smokers: a call to action.
AB  - The causative association between tobacco use and lung cancer is a well
      established fact. However, lung cancer also occurs, at surprisingly high rates,
      in lifelong never smokers. In fact, lung cancer in never smokers is among the
      leading causes of cancer-related mortality. This CCR Focus summarizes recent
      data, identifies knowledge deficits, and suggests future research directions with
      regard to this critically important subset of lung cancer patients.

PMID- 19755391
TI  - Lung cancer in never smokers: clinical epidemiology and environmental risk
      factors.
AB  - More than 161,000 lung cancer deaths are projected to occur in the United States
      in 2008. Of these, an estimated 10 to 15% will be caused by factors other than
      active smoking, corresponding to 16,000 to 24,000 deaths annually. Thus lung
      cancer in never smokers would rank among the most common causes of cancer
      mortality in the United States if considered as a separate category. Slightly
      more than half of the lung cancers caused by factors other than active smoking
      occur in never smokers. As summarized in the accompanying article, lung cancers
      that occur in never smokers differ from those that occur in smokers in their
      molecular profile and response to targeted therapy. These recent laboratory and
      clinical observations highlight the importance of defining the genetic and
      environmental factors responsible for the development of lung cancer in never
      smokers. This article summarizes available data on the clinical epidemiology of
      lung cancer in never smokers, and several environmental risk factors that
      population-based research has implicated in the etiology of these cancers.
      Primary factors closely tied to lung cancer in never smokers include exposure to
      known and suspected carcinogens including radon, second-hand tobacco smoke, and
      other indoor air pollutants. Several other exposures have been implicated.
      However, a large fraction of lung cancers occurring in never smokers cannot be
      definitively associated with established environmental risk factors, highlighting
      the need for additional epidemiologic research in this area.

PMID- 19755393
TI  - Wnt antagonist gene DKK2 is epigenetically silenced and inhibits renal cancer
      progression through apoptotic and cell cycle pathways.
AB  - PURPOSE: Wnt/beta-catenin signaling is involved in renal cancer. DKK2, a Wnt
      antagonist, is silenced in some cancers, although its function has not been
      investigated. We hypothesized that DKK2 may be epigenetically silenced and
      inhibits progression of renal cell carcinoma (RCC). EXPERIMENTAL DESIGN: RCC cell
      lines and a normal kidney cell line were used for methylation and chromatin
      immunoprecipitation assays. To assess various functions of DKK2, we established
      stable DKK2-transfected cells and examined them with regard to cell viability,
      colony formation, apoptosis, cell cycle, and invasive capability. A total of 52
      patients with confirmed conventional RCC were enrolled in this study. RESULTS:
      RCC cell lines had decreased levels of DKK2, which were significantly increased
      after treatment with 5-Aza-2'-deoxycytidine alone or 5-Aza-2'-deoxycytidine and
      trichostatin A. In chromatin immunoprecipitation assay, the levels of acetyl H3,
      acetyl H4, and dimethylated H3K4 were decreased, whereas the level of
      dimethylated H3K9 was increased in RCC cell lines compared with HK2 cells.
      Increased methylation in RCC tissues was associated with higher grades,
      pathologic stages, and pathologic tumor in RCC. Functional analysis showed that
      the numbers of viable A498 cells were significantly decreased in DKK2-transfected
      cells compared with mock cells. The number of apoptotic cells and S/G(2)-M phase
      cells was significantly increased and decreased after DKK2 transfection,
      respectively. Corresponding to these results, Bcl2 and cyclin D1 expression were
      also decreased in DKK2-overexpressing cells. CONCLUSION: DKK2 is epigenetically
      silenced by methylation in higher grades and stages of RCC. These results suggest
      that DKK2 inhibits renal cancer progression through apoptotic and cell cycle
      pathways.

PMID- 19755392
TI  - Lung cancer in never smokers: molecular profiles and therapeutic implications.
AB  - The majority of lung cancers are caused by long term exposure to the several
      classes of carcinogens present in tobacco smoke. Although a significant fraction
      of lung cancers in never smokers may also be attributable to tobacco, many such
      cancers arise in the absence of detectable tobacco exposure, and may follow a
      very different cellular and molecular pathway of malignant transformation. Recent
      studies summarized here suggest that lung cancers arising in never smokers have a
      distinct natural history, profile of oncogenic mutations, and response to
      targeted therapy. The majority of molecular analyses of lung cancer have focused
      on genetic profiling of pathways responsible for metabolism of primary tobacco
      carcinogens. Limited research has been conducted evaluating familial aggregation
      and genetic linkage of lung cancer, particularly among never smokers in whom such
      associations might be expected to be strongest. Data emerging over the past
      several years show that lung cancers in never smokers are much more likely to
      carry activating mutations of the epidermal growth factor receptor (EGFR), a key
      oncogenic factor and direct therapeutic target of several newer anticancer drugs.
      EGFR mutant lung cancers may represent a distinct class of lung cancers, enriched
      in the never-smoking population, and less clearly linked to direct tobacco
      carcinogenesis. These insights followed initial testing and demonstration of
      efficacy of EGFR-targeted drugs. Focused analysis of molecular carcinogenesis in
      lung cancers in never smokers is needed, and may provide additional biologic
      insight with therapeutic implications for lung cancers in both ever smokers and
      never smokers.

PMID- 19755394
TI  - Seeing is believing: on the use of image databases for visually exploring plant
      organelle dynamics.
AB  - Organelle dynamics vary dramatically depending on cell type, developmental stage
      and environmental stimuli, so that various parameters, such as size, number and
      behavior, are required for the description of the dynamics of each organelle.
      Imaging techniques are superior to other techniques for describing organelle
      dynamics because these parameters are visually exhibited. Therefore, as the
      results can be seen immediately, investigators can more easily grasp organelle
      dynamics. At present, imaging techniques are emerging as fundamental tools in
      plant organelle research, and the development of new methodologies to visualize
      organelles and the improvement of analytical tools and equipment have allowed the
      large-scale generation of image and movie data. Accordingly, image databases that
      accumulate information on organelle dynamics are an increasingly indispensable
      part of modern plant organelle research. In addition, image databases are
      potentially rich data sources for computational analyses, as image and movie data
      reposited in the databases contain valuable and significant information, such as
      size, number, length and velocity. Computational analytical tools support image
      based data mining, such as segmentation, quantification and statistical analyses,
      to extract biologically meaningful information from each database and combine
      them to construct models. In this review, we outline the image databases that are
      dedicated to plant organelle research and present their potential as resources
      for image-based computational analyses.

PMID- 19755395
TI  - Arrested differentiation of proplastids into chloroplasts in variegated leaves
      characterized by plastid ultrastructure and nucleoid morphology.
AB  - Leaf variegation is seen in many ornamental plants and is often caused by a cell
      lineage type formation of white sectors lacking functional chloroplasts. A mutant
      showing such leaf variegation is viable and is therefore suitable for studying
      chloroplast development. In this study, the formation of white sectors was
      temporally investigated in the Arabidopsis leaf-variegated mutant var2. Green
      sectors were found to emerge from white sectors after the formation of the first
      true leaf. Transmission electron microscopic examination of plastid
      ultrastructures confirmed that the peripheral zone in the var2 shoot meristem
      contained proplastids but lacked developing chloroplasts that were normally
      detected in wild type. These data suggest that chloroplast development proceeds
      very slowly in var2 variegated leaves. A notable feature in var2 is that the
      plastids in white sectors contain remarkable globular vacuolated membranes and
      prolamellar body-like structures. Although defective plastids were hardly
      observed in shoot meristems, they began to accumulate during early leaf
      development. Consistent with these observations, large plastid nucleoids detected
      in white sectors by DNA-specific fluorescent dyes were characteristic of those
      found in proplastids and were clearly distinguished from those in chloroplasts.
      These results strongly imply that in white sectors, differentiation of plastids
      into chloroplasts is arrested at the early stage of thylakoid development.
      Interestingly, large plastid nucleoids were detected in variegated sectors from
      species other than Arabidopsis. Thus, plastids in variegated leaves appear to
      share a common feature and represent a novel plastid type.

PMID- 19755396
TI  - Risk of cancer among hairdressers and related workers: a meta-analysis.
AB  - BACKGROUND: Hairdressers and allied occupations represent a large and fast
      growing group of professionals. The fact that these professionals are chronically
      exposed to a large number of chemicals present in their work environment,
      including potential carcinogens contained in hair dyes, makes it necessary to
      carry out a systematic evaluation of the risk of cancer in this group. METHODS:
      We retrieved studies by systematically searching Medline and other computerized
      databases, and by manually examining the references of the original articles and
      monographs retrieved. We also contacted international researchers working on this
      or similar topics to complete our search. We included 247 studies reporting
      relative risk (RR) estimates of hairdresser occupation and cancer of different
      sites. RESULTS: Study-specific RRs were weighted by the inverse of their variance
      to obtain fixed and random effects pooled estimates. The pooled RR of
      occupational exposure as a hairdresser was 1.27 (95% CI 1.15-1.41) for lung
      cancer, 1.52 [95% confidence interval (CI) 1.11-2.08] for larynx cancer, 1.30
      (95% CI 1.20-1.42) for bladder cancer and 1.62 (95% CI 1.22-2.14) for multiple
      myeloma. Data for other anatomic sites showed increases of smaller magnitude. The
      results restricted to those studies carried out before the ban of two major
      carcinogens from hair dyes in the mid-1970s were similar to the general results.
      CONCLUSIONS: Hairdressers have a higher risk of cancer than the general
      population. Improvement of the ventilation system in the hairdresser salons and
      implementation of hygiene measures aimed at mitigating exposure to potential
      carcinogens at work may reduce the risk.

PMID- 19755397
TI  - Commentary: Reducing HIV-associated tuberculosis in children.

PMID- 19755398
TI  - Are kinking and coiling of carotid artery congenital or acquired?
AB  - Dolichoarteriopathies consist of tortuosity, kinking, or coiling of the
      extracranial carotid arteries. Some authors consider these alterations a
      consequence of atherosclerotic vessel remodeling, while others ascribe them to
      anatomical variations of embryological origin. The objective was to establish
      whether carotid dolichoarteriopathies belonged to a congenital origin or to
      acquired conditions. Color Doppler ultrasonography of neck vessels was performed
      in 885 participants, whose age ranged from 1-day-old infants to 90-year-old
      adults. Prevalence of kinking and coiling was evaluated, and it was related to
      the presence of cardiovascular risk factors. Prevalence of either kinking or coil
      of carotid arteries showed no increase with age, as it was comparable across all
      ages; furthermore, frequency of these alterations showed no relationship to
      cardiovascular risk factors nor to the presence of atheromatous plaques. These
      findings suggest that carotid dolichoarteriopathies are a result of alterations
      in embryological development rather than vascular remodeling secondary to aging
      and/or atherosclerosis.

PMID- 19755399
TI  - Urgent segmental resection as the primary strategy in management of benign
      tracheal stenosis. A single center experience in 164 consecutive cases.
AB  - The report is a retrospective review of 238 benign tracheal stenoses of various
      etiologies treated between 1995 and 2008. To show that urgent segmental resection
      has complication rates similar to elective resection and, therefore, preoperative
      dilation is not necessary, we analysed records of patients who underwent either
      standard segmental resections with anterolateral mediastinal tracheal
      mobilization, single-suture anastomosis and neck flexion; or insertion of T-tube
      with oval-shaped horizontal arm. Primary segmental resection was performed in 164
      patients (68.9%), including 14 cases with concomitant tracheo-esophageal fistula
      (TEF). T-tube as an initial treatment suited 74 (31.1%) patients. We encountered
      two partial and one complete anastomotic disruptions following subglottic
      resections treated by T-tube insertion and costal cartilage tracheoplasty or
      permanent tracheostomy. Restenosis rate in segmental resection was 3.1%. No
      difference in complication rate between urgent and elective segmental resections
      was experienced. We treated a small number of patients by endotracheal stent
      insertion but the results were discouraging. Urgent segmental resection without
      prior rigid bronchoscopy dilation is our strategy of choice whenever possible. As
      an alternative to dilation we prefer temporary insertion of modified T-tube.
      Stand-alone endoluminal dilation and stenting has yet to prove its safety and
      long-term efficacy.

PMID- 19755400
TI  - Left paraxiphoidian approach for drainage of pericardial effusions.
AB  - Pericardial effusion is one of the frequent complications of malignancies, up to
      15-20% of the autopsy specimens showing pericardial or cardiac metastasis. Often
      the pericardial fluid accumulates in large quantities leading to cardiac
      tamponade, which can be fatal in the absence of appropriate treatment. The
      authors present another type of pericardial drainage: the approach is
      paraxiphoidian, not subxiphoidian or with xiphoid resection. Without xiphoid
      process resection, the surgery is better tolerated by patients (frequently the
      drainage is made under local anesthesia). In the case of xiphoid preservation,
      the surgical intervention is easier (no need for hard retraction of this bone).
      In all the five cases with this access, the postoperative results were very good,
      with complete evacuation of pericardial effusion. In all the cases, the
      pericardial biopsy performed under visual control was sufficient for a
      histological diagnosis and the immunohistochemical tests, if required.

PMID- 19755401
TI  - Syncope triggered by a giant unruptured sinus of Valsalva aneurysm.
AB  - Sinus of Valsalva aneurysms are rare anomalies, most often caused by congenital
      absence of muscular and elastic tissue in the aortic wall of the sinus. The
      indication for surgical repair is controversial at the time of diagnosis. As
      well, the repair technique depends on how many sinuses are dilated, whether the
      aneurysm is ruptured and whether the aneurysm is symptomatic. We report a case of
      a single unruptured sinus of Valsalva aneurysm of a 54-year-old woman.

PMID- 19755402
TI  - Tirofiban as adjunctive therapy for acute coronary syndromes and percutaneous
      coronary intervention: a meta-analysis of randomized trials.
AB  - AIMS: To perform a thorough and updated systematic review of randomized clinical
      trials comparing tirofiban vs. placebo or vs. abciximab. METHODS AND RESULTS: We
      searched for randomized trials comparing tirofiban vs. placebo or any active
      control. Odds ratios (OR) were computed from individual studies and pooled with
      random-effect methods. Thirty-one studies were identified involving 20,006
      patients (12 874 comparing tirofiban vs. heparin plus placebo or bivalirudin
      alone, and 7132 vs. abciximab). When compared with placebo, tirofiban was
      associated at 30 days with a significant reduction in mortality [OR = 0.68 (0.54
      0.86); P = 0.001] and death or myocardial infarction (MI) [OR = 0.69 (0.58-0.81);
      P < 0.001]. The treatment benefit persisted at follow-up but came at an increased
      risk of minor bleedings [OR = 1.42 (1.13, 1.79), P = 0.002] or thrombocytopenia.
      When compared with abciximab, mortality at 30 days did not differ [OR = 0.90
      (0.53, 1.54); P = 0.70], but in the overall group tirofiban trended to increase
      the composite of death or MI [OR = 1.18 (0.96, 1.45); P = 0.11]. No such trend
      persisted at medium-term follow-up or when appraising studies testing tirofiban
      at 25 microg/kg bolus regimen. CONCLUSION: Tirofiban administration reduces
      mortality, the composite of death or MI and increases minor bleedings when
      compared with placebo. An early ischaemic hazard disfavouring tirofiban was noted
      when compared with abciximab in studies based on 10 but not 25 microg/kg
      tirofiban bolus regimen.

PMID- 19755403
TI  - Fish intake and acute coronary syndrome.
AB  - AIMS: To study the effect of fish consumption on the risk of acute coronary
      syndrome (ACS) in healthy subjects. METHODS AND RESULTS: This Danish follow-up
      study included 57,053 men and women between 50 and 64 years. Intake of lean and
      fatty fish was estimated from a detailed and validated food frequency
      questionnaire. Potential cases of ACS were identified through nationwide medical
      databases. A total of 1122 cases of ACS were verified during a mean follow-up
      period of 7.6 years. Among men, intake of fatty fish was associated with a lower
      risk of ACS. For men in the highest quintile of fish intake compared with the
      lowest quintile, the hazard ratio was 0.67 (95% confidence interval: 0.53-0.85).
      The inverse association was observed for intakes >6 g of fatty fish per day with
      no obvious additional benefit observed for higher intakes. Intake of lean fish
      was not associated with ACS. There were few cases of ACS and results were not
      consistent in women. CONCLUSION: In conclusion, a modest intake of fatty fish was
      associated with a lower risk of ACS in middle-aged men, whereas no consistent
      associations were observed among women.

PMID- 19755404
TI  - Synaptophysin immunoreactivity in adrenocortical adenomas: a correlation between
      synaptophysin and CYP17A1 expression.
AB  - DESIGN AND METHODS: The adrenal cortex is not considered to be an intrinsic part
      of the diffuse neuroendocrine system, but adrenocortical neoplasms possess
      neuroendocrine properties. In this study, we examined synaptophysin (SYP) and
      neural cell adhesion molecule (NCAM) expression in adrenocortical adenomas in
      relation to adrenal function. RESULTS: Immunohistochemical analysis showed that
      50.7 and 98.6% of the cortical adenomas showed SYP and NCAM immunoreactivities
      respectively. There was no apparent difference in NCAM immunoreactivity among the
      adenomas. However, the immunostaining for SYP was significantly stronger in
      cortisol-producing adenomas (CPA) than in aldosterone-producing adenomas (APA),
      nonfunctioning adenomas (NFA), showing no clinical or endocrinological
      abnormality, or adenomas associated with preclinical Cushing's syndrome (preCS).
      Western blotting and real-time PCR demonstrated that the expression level of SYP
      protein and mRNA was significantly higher in CPA than in APA or NFA.
      Additionally, the SYP mRNA level showed a positive correlation with CYP17A1 mRNA.
      In addition to the plasma membrane, mitochondria, and smooth endoplasmic
      reticulum, SYP immunoreactivity was detected in the Golgi area, which is known to
      be involved in the regulation of mitochondrial cholesterol and the transport of
      steroid intermediates. It was unexpected that the ratio of positive cells for SYP
      in preCS was less than that in APA and NFA. However, further examination is
      required, because the number of preCS cases we investigated was very small.
      CONCLUSIONS: We propose that SYP expression in adrenocortical cells may be
      involved in some aspect of adrenal function such as transport or secretion of
      glucocorticoids.

PMID- 19755405
TI  - Total and high molecular weight adiponectin are elevated in patients with Laron
      syndrome despite marked obesity.
AB  - OBJECTIVE: Patients with Laron syndrome (LS; primary GH insensitivity) caused by
      molecular defects of the GH receptor gene, are characterized by dwarfism,
      profound obesity, and hyperlipidemia. The aim of the current study was to
      evaluate adiponectin levels in LS, as obesity is known to be associated with low
      adiponectin. DESIGN AND METHODS: We studied nine untreated LS adult patients (5
      males, 4 females) and six girls with LS receiving once-daily treatment by IGF1.
      Total and high molecular weight (HMW) adiponectin levels, adiponectin multimers
      distribution, and metabolic indices were analyzed in serum samples obtained
      during several years of follow-up. RESULTS: Adiponectin levels in the severely
      obese adult LS patients (percent body fat; females 61.0+/-2.5%, males 40.6+/
      8.1%) were two- to three-fold higher than those reported for subjects of
      corresponding age, gender and degree of adiposity. Total adiponectin was
      significantly higher in females compared with males (21.4+/-3.5 vs 10.2+/-4.6
      microg/ml, P<0.001). The elevated adiponectin in LS subjects was associated with
      an increased abundance of the HMW isoform, and positively correlated with body
      fat percentage (r=0.65, P=0.017) and leptin (r=0.65, P=0.012). There was no
      correlation between adiponectin levels (total and HMW) and the degree of insulin
      resistance in LS subjects or their blood lipids levels. Adiponectin was also high
      in young girls with LS (22.9+/-7.4 microg/ml) and did not change during long-term
      IGF1 replacement therapy. CONCLUSION: Adiponectin hypersecretion in LS, despite
      profound obesity, suggests that GH activity may negatively impact adiponectin
      secretion from adipocytes.

PMID- 19755406
TI  - Treated hypothyroidism, cognitive function, and depressed mood in old age: the
      Rancho Bernardo Study.
AB  - OBJECTIVE: Overt hypothyroidism is associated with cognitive impairment, which
      can be reversed if treated early and appropriately. We compared cognitive
      function (CF) of euthyroid older adults with those who had long-term treated
      hypothyroidism. METHODS: Between 1999 and 2003, the CF of 885 euthyroid and 149
      hypothyroid-treated older adults (primary hypothyroidism after surgery or
      autoimmune thyroid disease) was assessed using three standardized CF tests: the
      modified mini-mental state examination, Trails B, and verbal fluency. Depressed
      mood was assessed using the Beck Depression Inventory (BDI). Only participants
      with thyroid stimulating hormone (TSH) in the normal range were included.
      RESULTS: The treated hypothyroid group had been treated with l-thyroxine for an
      average of 20 years. Those with treated hypothyroidism were older than the
      euthyroid group (76.1+/-9.6 vs 73.6+/-10.2 years, P=0.005) and were much more
      often women (81.6 vs 54.8%, P<0.001). TSH levels were similar between groups
      (median interquartile range=1.57 (1.19) vs 1.54 (1.59) mIU/l, P=0.81). Compared
      to euthyroid, the treated hypothyroidism group had more frequent antidepressant
      medication use (19.5 vs 8.5%, P<0.001) but similar BDI scores. Performance on the
      three CF tests did not differ by thyroid hormone treatment. Results were not
      changed after adjustment for age, sex, antidepressant medication use, exercise,
      and total cholesterol. CONCLUSION: Long-term treated hypothyroidism is not
      associated with impaired CF or depressed mood in old age. The lack of association
      with CF is reassuring with regard to long-term use of thyroid hormone therapy.

PMID- 19755407
TI  - Association of the +45T>G and +276G>T polymorphisms in the adiponectin gene with
      insulin resistance in nondiabetic Greek women.
AB  - OBJECTIVE: We explored potential associations of two single nucleotide
      polymorphisms (SNPs) in the adiponectin gene (ADIPOQ; +45T>G, rs2241766 and
      +276G>T, rs1501299) with circulating total and high-molecular weight (HMW)
      adiponectin, insulin resistance (IR), and markers of obesity in a healthy Greek
      female population. DESIGN AND METHODS: The two SNPs were genotyped in 349 women
      without diabetes (mean age: 47.0+/-12.1 years, mean body mass index: 28.9+/-5.6
      kg/m(2)). Total and HMW adiponectin concentrations, body composition variables,
      IR parameters, and plasma lipid levels were determined. RESULTS: In single SNP
      analysis adjusting for several potential confounders, SNP +276G>T was associated
      with higher fasting insulin levels (P=0.01) and higher homeostasis model
      assessment index for IR (HOMA-IR; P=0.009), and SNP +45T>G was associated with
      lower insulin levels and HOMA-IR (P=0.05 and P=0.07 respectively). No association
      with total or HMW adiponectin, plasma lipid levels, and body composition
      variables was observed; however, haplotype analysis revealed that subjects
      homozygous for the most common +45T/+276G haplotype had lower total adiponectin
      levels than did noncarriers of this haplotype (P=0.02). The observed differences
      in HOMA-IR were very significant among women with a higher body fat (BF)
      percentage (>or= the population median of 41%; all P<or=0.005), but not among
      leaner individuals (P for interactions 0.01-0.07), thus suggesting that ADIPOQ
      effects on insulin sensitivity may depend upon BF status. CONCLUSION: Our data
      suggest a significant role of ADIPOQ variants at positions +45 and +276 in the
      development of IR in healthy Greek women possibly through an interaction with BF.

PMID- 19755408
TI  - Therapeutic analysis in Chinese patients with thyrotoxic periodic paralysis over
      6 years.
AB  - OBJECTIVE: To characterize the course of therapy in a large cohort of Chinese
      patients with thyrotoxic periodic paralysis (TPP), a reversible electrolyte
      emergency fraught with therapeutic challenges. DESIGN AND METHODS: In this
      prospective interventional study, 78 patients with TPP (75 males and three
      females with an age range of 16-48 years) were consecutively enrolled over a 6
      year period. Intravenous KCl at a rate of 10 mmol/h was administered until muscle
      strength recovered. Serum potassium (K(+)) and phosphorus concentrations were
      measured hourly during the paralytic attack and for 6 h after recovery. RESULTS:
      The serum potassium (K(+)) on attack was 2.1+/-0.2 mmol/l. The dose of KCl
      administered to restore muscle strength was 63+/-32 mmol, and peak serum K(+)
      concentration after recovery was 5.3+/-0.5 mmol/l. A paradoxical fall in serum
      K(+) concentration >0.1 mmol/l difference between presentation and treatment
      nadir was observed in approximately one-fourth of TPP patients (n=20). These
      patients had significantly higher serum-free thyroxine concentration, systolic
      blood pressure, and heart rate on presentation, as well as serum phosphate
      concentration on recovery. They not only needed much more KCl supplementation
      (104+/-34 vs 48+/-19 mmol, P<0.001), but also had significantly more severe
      rebound hyperkalemia (5.8+/-0.5 vs 5.1+/-0.4 mmol/l, P<0.001) on recovery than
      those who did not have paradoxical hypokalemia. There was a positive correlation
      between the dose of KCl administered and the difference between peak and nadir
      serum K(+) (Delta K(+)) (r=0.68, P<0.001). CONCLUSIONS: TPP patients who do not
      develop paradoxical hypokalemia need a smaller KCl dose to achieve recovery,
      whereas those who develop paradoxical hypokalemia have more severe
      hyperthyroidism and hyperadrenergic activity and may require blockage of
      intracellular K(+) shift to prevent rebound hyperkalemia.

PMID- 19755409
TI  - Pioglitazone improves insulin resistance and decreases blood pressure in adult
      patients with congenital adrenal hyperplasia.
AB  - CONTEXT: Patients with congenital adrenal hyperplasia (CAH) are chronically
      treated with supraphysiological doses of glucocorticoids, which are known to
      induce insulin resistance. Thiazolidinediones might reverse this effect and
      improve insulin sensitivity. OBJECTIVES: To assess insulin sensitivity in CAH
      patients and the effect of pioglitazone treatment on insulin sensitivity in CAH
      patients. Secondary objectives were the effects of treatment with pioglitazone on
      blood pressure, body fat distribution, lipid, and steroid profiles. DESIGN:
      Randomized placebo controlled crossover trial. PARTICIPANTS: Twelve CAH patients
      and 12 body mass and age-matched control subjects. INTERVENTION: Sixteen-week
      treatment with pioglitazone (45 mg/day) or placebo. MAIN OUTCOME MEASURE: Insulin
      sensitivity measured by euglycemic clamp and oral glucose tolerance test. Further
      measures were 24-h blood pressure profiles, body fat distribution measured by
      magnetic resonance imaging, dual energy x-ray absorptiometry (DEXA) and
      bioimpedance procedures, liver fat by magnetic resonance spectroscopy, lipid, and
      steroid profiles. RESULTS: CAH patients were insulin resistant compared with
      healthy controls. Treatment with pioglitazone significantly improved insulin
      sensitivity in CAH patients (glucose infusion rate (GIR) from 28.5+/-11.6 to
      38.9+/-11.0 micromol/kg per min, P=0.000, GIR in controls 46.2+/-23.4 micromol/kg
      per min, P<0.05 versus CAH). Treatment with pioglitazone decreased blood pressure
      (systolic: 124.0+/-13.6 vs 127.0+/-14.9 mmHg, P<0.001, diastolic: 72.8+/-11.5 vs
      77.4+/-12.6 mmHg, P<0.001). No changes in body fat distribution, lipid, and
      steroid profiles were observed. CONCLUSIONS: CAH patients are insulin resistant
      compared with matched control subjects. Treatment with pioglitazone improves
      insulin sensitivity and decreases blood pressure in CAH patients.

PMID- 19755410
TI  - Insulinotropic actions of nateglinide in type 2 diabetic patients and effects on
      dipeptidyl peptidase-IV activity and glucose-dependent insulinotropic polypeptide
      degradation.
AB  - BACKGROUND: Nateglinide restores early-phase insulin secretion to feeding and
      reduces postprandial hyperglycaemia in type 2 diabetes. This study evaluated the
      effects of nateglinide on dipeptidyl peptidase-IV (DPP-IV) activity and glucose
      dependent insulinotropic polypeptide (GIP) degradation. Research design and
      methods Blood samples were collected from type 2 diabetic subjects (n=10, fasting
      glucose 9.36+/-1.2 mmol/l) following administration of oral nateglinide (120 mg)
      10 min prior to a 75 g oral glucose load in a randomised crossover design.
      RESULTS: Plasma glucose reached 18.2+/-1.7 and 16.7+/-1.7 mmol/l at 90 min in
      control and placebo groups (P<0.001). These effects were accompanied by prompt
      32% inhibition of DPP-IV activity after 10 min (19.9+/-1.6 nmol/ml per min,
      P<0.05), reaching a minimum of 1.9+/-0.1 nmol/ml per min at 120 min (P<0.001)
      after nateglinide. Insulin and C-peptide levels increased significantly compared
      with placebo, to peak after 90 min at 637.6+/-163.9 pmol/l (P<0.05) and 11.8+/
      1.4 mg/l (P<0.01) respectively. DPP-IV-mediated degradation of GIP was
      significantly less in patients receiving nateglinide compared with placebo.
      Inhibition of DPP-IV activity corresponded with a time- and concentration
      dependent inhibitory effect of nateglinide on DPP-IV-mediated truncation of GIP(1
      42) to GIP(3-42) in vitro. Comparison of in vitro inhibition of DPP-IV by
      nateglinide and vildagliptin revealed IC(50) values of 17.1 and 2.1 microM
      respectively. CONCLUSIONS: Although considerably less potent than specified DPP
      IV inhibitors, the possibility that some of the beneficial actions of nateglinide
      are indirectly mediated through DPP-IV inhibition and increased bioavailability
      of GIP and other incretins merits consideration.

PMID- 19755411
TI  - Peripheral insulin-like factor 3 concentrations are reduced in men with type 2
      diabetes mellitus: effect of glycemic control and visceral adiposity on Leydig
      cell function.
AB  - BACKGROUND AND AIM: Hypogonadism frequently occurs in men with type 2 diabetes
      mellitus (T2DM), while the role of glycemic control and visceral obesity is still
      unclear. This study aimed to assess the Leydig cell function, including the new
      sensitive marker insulin-like factor 3 (INSL3), in T2DM patients without overt
      hypogonadism and the influence of either glycemic control or visceral adiposity.
      SUBJECTS AND METHODS: Thirty T2DM patients (age 57.1+/-6.2 years, body mass index
      (BMI) 28.0+/-4.3) without overt hypogonadism and 30 age- and BMI-matched controls
      were studied. Anthropometric, glycometabolic parameters and testosterone, SHBG,
      LH, INSL3 levels, bioavailable and free testosterone (BT and cFT) were evaluated.
      The human chorionic gonadotrophin (hCG) test was also performed. RESULTS:
      Patients had lower total testosterone (452.6+/-130.0 vs 512.6+/-117.3 ng/dl,
      P=0.06), BT (189.7+/-36.4 vs 237.1+/-94.1 ng/dl, P=0.002), cFT (8.1+/-1.6 vs
      10.1+/-4.0 ng/dl, P=0.002), and higher LH levels (3.5+/-1.6 vs 2.6+/-1.2 mU/ml,
      P=0.01) versus controls. Serum INSL3 concentrations were also lower in patients
      (1.1+/-0.3 vs 1.5+/-0.7 ng/ml, P=0.01). These hormonal parameters, including
      INSL3, did not differ between T2DM patients with poor or good glycemic control
      (HbA1c>9 or <7% respectively). In patients, waist circumferences (97.9+/-12.4 cm)
      negatively correlated with INSL3 (P=0.03) and basal, as well as hCG-stimulated
      testosterone levels (P=0.04 and 0.004 respectively). Basal or stimulated hormonal
      levels and INSL3 concentrations were not different between patients with (40%) or
      without erectile dysfunction. CONCLUSIONS: An early impairment of the overall
      Leydig cell function is present in men with T2DM, mainly related to visceral
      adiposity rather than to glycemic control.

PMID- 19755412
TI  - An in vitro selection strategy for conferring protease resistance to ligand
      binding peptides.
AB  - One drawback to the use of peptides as therapeutics has been their susceptibility
      to proteolysis. Here, we have used an in vitro display technology, CIS display,
      to enhance the proteolytic resistance of ligand-binding peptides by selection of
      protecting motifs from a large peptide library. The premise to this selection was
      that certain linear peptides within a library could form structures capable of
      preventing the access of proteases to defined cleavage sites without affecting
      ligand binding. A diverse 12-mer peptide library was inserted between a FLAG
      epitope motif and a thrombin cleavage site and this construct was fused to the
      bacterial initiator protein RepA for CIS display selection. After five rounds of
      selection, protection motifs were isolated that were capable of preventing
      proteolytic cleavage of the adjacent thrombin site. Some of the selected peptides
      were also resistant to more promiscuous proteases, such as chymotrypsin and
      trypsin, which were not used in the selection. The observed resistance to
      thrombin, trypsin and chymotrypsin translated into increased resistance to plasma
      proteases in vitro and to an increase in circulating half-lives in rats. This
      method can be applied to enhancing the in vivo stability of therapeutic peptides.

PMID- 19755413
TI  - S1P3-mediated cardiac fibrosis in sphingosine kinase 1 transgenic mice involves
      reactive oxygen species.
AB  - AIMS: Sphingosine kinase 1 (SPHK1), its product sphingosine-1-phosphate (S1P),
      and S1P receptor subtypes have been suggested to play protective roles for
      cardiomyocytes in animal models of ischaemic preconditioning and cardiac
      ischaemia/reperfusion injury. To get more insight into roles for SPHK1 in vivo,
      we have generated SPHK1-transgenic (TG) mice and analysed the cardiac phenotype.
      METHODS AND RESULTS: SPHK1-TG mice overexpressed SPHK1 in diverse tissues, with a
      nearly 20-fold increase in enzymatic activity. The TG mice grew normally with
      normal blood chemistry, cell counts, heart rate, and blood pressure.
      Unexpectedly, TG mice with high but not low expression levels of SPHK1 developed
      progressive myocardial degeneration and fibrosis, with upregulation of embryonic
      genes, elevated RhoA and Rac1 activity, stimulation of Smad3 phosphorylation, and
      increased levels of oxidative stress markers. Treatment of juvenile TG mice with
      pitavastatin, an established inhibitor of the Rho family G proteins, or deletion
      of S1P3, a major myocardial S1P receptor subtype that couples to Rho GTPases and
      transactivates Smad signalling, both inhibited cardiac fibrosis with concomitant
      inhibition of SPHK1-dependent Smad-3 phosphorylation. In addition, the anti
      oxidant N-2-mercaptopropyonylglycine, which reduces reactive oxygen species
      (ROS), also inhibited cardiac fibrosis. In in vivo ischaemia/reperfusion injury,
      the size of myocardial infarct was 30% decreased in SPHK1-TG mice compared with
      wild-type mice. CONCLUSION: These results suggest that chronic activation of
      SPHK1-S1P signalling results in both pathological cardiac remodelling through ROS
      mediated by S1P3 and favourable cardioprotective effects.

PMID- 19755414
TI  - Effect of telithromycin on the pharmacokinetics and pharmacodynamics of oral
      oxycodone.
AB  - The aim of this study is to determine whether the inhibition of CYP2D6 and CYP3A4
      enzyme activity with telithromycin affects the pharmacokinetics and
      pharmacodynamics of orally administered oxycodone in a randomized 2-phase
      crossover study. Eleven healthy subjects were pretreated with 800 mg of oral
      telithromycin or placebo for 4 days. On day 3, they ingested 10 mg of immediate
      release oxycodone. Plasma concentrations of oxycodone and its oxidative
      metabolites were measured for 48 hours, and pharmacodynamic effects were
      evaluated. Telithromycin increased the area under the plasma concentration-time
      curve (AUC(0-infinity)) of oxycodone by 80% (P < .001) and reduced the AUC(0
      infinity) of noroxycodone by 46% (P < .001). Most of the pharmacokinetic changes
      were seen in the elimination phase, with little effect by telithromycin on the
      peak concentration of oxycodone. Pharmacodynamic effects of oxycodone were
      modestly enhanced by telithromycin. In conclusion, telithromycin clearly reduces
      the N-demethylation of oxycodone to noroxycodone by inhibiting the CYP450 3A4
      enzyme. The use of telithromycin in patients receiving multiple doses of
      oxycodone for pain relief may increase the risk of opioid adverse effects.
      Reduction of oxycodone dose by 25% to 50% followed by readjustment according to
      the clinical response might be appropriate.

PMID- 19755415
TI  - Acute hemodynamic effects of single-dose sildenafil when added to established
      bosentan therapy in patients with pulmonary arterial hypertension: results of the
      COMPASS-1 study.
AB  - This study investigated the acute pharmacodynamic effects of sildenafil in
      patients with pulmonary arterial hypertension (PAH) and concomitant bosentan
      treatment, in view of a mutual pharmacokinetic interaction between the 2 drugs.
      This prospective, open-label, noncomparative, multicenter, phase II study
      enrolled 45 patients (>or=18 years) with stable PAH (idiopathic, familial, or
      related to corrected congenital systemic-to-pulmonary shunts, drugs, or toxins)
      and on bosentan treatment for at least 3 months. Patients underwent right heart
      catheterization to evaluate the acute hemodynamic effects of (a) inhaled nitric
      oxide (iNO) and (b) a single oral dose of sildenafil (25 mg). Mean pulmonary
      vascular resistance (PVR) decreased from baseline following iNO (-15%; 95%
      confidence limits: -21%, -8%; P = .0001). A statistically significant decrease
      from baseline in mean PVR was also observed 60 minutes following sildenafil
      administration (-15%; 95% confidence limits: -21%, -10%; P < .0001). The
      reduction in PVR following sildenafil was comparable to that resulting from iNO.
      There were no unexpected safety findings. The pharmacodynamic effect suggests
      that addition of sildenafil to bosentan treatment can elicit additional
      hemodynamic benefits. These data represent a rationale for long-term combination
      studies with the 2 compounds.

PMID- 19755416
TI  - Docosahexaenoic acid enhances hepatic serum amyloid A expression via protein
      kinase A-dependent mechanism.
AB  - Serum amyloid A (SAA) reduces fat deposition in adipocytes and hepatoma cells.
      Human SAA1 mRNA is increased by docosahexaenoic acid (DHA) treatment in human
      cells. These studies asked whether DHA decreases fat deposition through SAA1 and
      explored the mechanisms involved. We demonstrated that DHA increased human SAA1
      and C/EBPbeta mRNA expression in human hepatoma cells, SK-HEP-1. Utilizing a
      promoter deletion assay, we found that a CCAAT/enhancer-binding protein beta
      (C/EBPbeta)-binding site in the SAA1 promoter region between -242 and -102 bp was
      critical for DHA-mediated SAA1 expression. Mutation of the putative C/EBPbeta
      binding site suppressed the DHA-induced SAA1 promoter activity. The addition of
      the protein kinase A inhibitor H89 negated the DHA-induced increase in C/EBPbeta
      protein expression. The up-regulation of SAA1 mRNA and protein by DHA was also
      inhibited by H89. We also demonstrated that DHA increased protein kinase A (PKA)
      activities. These data suggest that C/EBPbeta is involved in the DHA-regulated
      increase in SAA1 expression via PKA-dependent mechanisms. Furthermore, the
      suppressive effect of DHA on triacylglycerol accumulation was abolished by H89 in
      SK-HEP-1 cells and adipocytes, indicating that DHA also reduces lipid
      accumulation via PKA. The observation of increased SAA1 expression coupled with
      reduced fat accumulation mediated by DHA via PKA suggests that SAA1 is involved
      in DHA-induced triacylglycerol breakdown. These findings provide new insights
      into the complicated regulatory network in DHA-mediated lipid metabolism and are
      useful in developing new approaches to reduce body fat deposition and fatty
      liver.

PMID- 19755417
TI  - Proximity-based protein thiol oxidation by H2O2-scavenging peroxidases.
AB  - H(2)O(2) acts as a signaling molecule by oxidizing critical thiol groups on redox
      regulated target proteins. To explain the efficiency and selectivity of H(2)O(2)
      based signaling, it has been proposed that oxidation of target proteins may be
      facilitated by H(2)O(2)-scavenging peroxidases. Recently, a peroxidase-based
      protein oxidation relay has been identified in yeast, namely the oxidation of the
      transcription factor Yap1 by the peroxidase Orp1. It has remained unclear whether
      the protein oxidase function of Orp1 is a singular adaptation or whether it may
      represent a more general principle. Here we show that Orp1 is in fact not
      restricted to oxidizing Yap1 but can also form a highly efficient redox relay
      with the oxidant target protein roGFP (redox-sensitive green fluorescent protein)
      in mammalian cells. Orp1 mediates near quantitative oxidation of roGFP2 by
      H(2)O(2), and the Orp1-roGFP2 redox relay effectively converts physiological
      H(2)O(2) signals into measurable fluorescent signals in living cells.
      Furthermore, the oxidant relay phenomenon is not restricted to Orp1 as the
      mammalian peroxidase Gpx4 also mediates oxidation of proximal roGFP2 in living
      cells. Together, these findings support the concept that certain peroxidases
      harbor an intrinsic and powerful capacity to act as H(2)O(2)-dependent protein
      thiol oxidases when they are recruited into proximity of oxidizable target
      proteins.

PMID- 19755418
TI  - 12-O-tetradecanoylphorbol-13-acetate inhibits melanoma growth by inactivation of
      STAT3 through protein kinase C-activated tyrosine phosphatase(s).
AB  - The growth of most melanoma cells in vitro is inhibited by the tumor-promoting
      phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). In this study, the
      involvement of the signal transducer and activator of transcription 3 (STAT3) in
      the TPA-induced growth inhibition of melanoma cells was examined. The in vitro
      growth and DNA synthesis of five melanoma cell lines, whose STAT3 was activated
      (phosphorylated), was inhibited by TPA, whereas that of WM35 and WM39 cells,
      whose STAT3 activity was at negligible levels, was considerably slow and not
      affected by TPA. Blockade of STAT3 activity by small interfering RNAs suppressed
      the growth of WM1205Lu cells containing constitutively activated STAT3. Treatment
      of WM1205Lu cells with TPA decreased both the phosphorylated STAT3 and the DNA
      binding activity of STAT3. Pretreatment of WM1205Lu cells with either a protein
      tyrosine phosphatase inhibitor or a protein kinase C (PKC) inhibitor prevented
      the inhibitory effects of TPA on the level of phosphorylated STAT3. The five
      melanoma cell lines containing phosphorylated STAT3 commonly expressed PKCalpha,
      PKCdelta, and PKCepsilon. Introduction of the dominant negative mutant of one of
      these PKC isoforms into WM1205Lu cells inhibited the TPA-induced
      dephosphorylation of STAT3. A Src inhibitor attenuated the STAT3 phosphorylation
      in WM1205Lu cells. These results indicate that constitutively activated STAT3 is
      positively regulated by c-Src and negatively regulated by a PKC-activated
      tyrosine phosphatase(s) in melanoma cells. Because TPA did not affect c-Src
      activity, we conclude that the growth inhibitory effect of TPA on melanoma cells
      is mediated through inactivation of STAT3 by a PKC-activated tyrosine
      phosphatase(s).

PMID- 19755419
TI  - Proteolytic cleavage of type I collagen generates an autoantigen in autoimmune
      uveitis.
AB  - This study was initiated to induce experimental autoimmune anterior uveitis
      (EAAU) in Lewis rats by melanin-associated antigen (MAA; 22-kDa fragment of type
      I collagen alpha2 chain) derived from rat iris and ciliary body (CB), to localize
      MAA within the eye, and to investigate the possible mechanism of MAA generation
      in vivo. The EAAU model replicates idiopathic human anterior uveitis. Lewis rats
      sensitized to rat MAA developed anterior uveitis, and EAAU induced by rat MAA can
      be adoptively transferred to naive syngenic rats by MAA-primed T cells. Animals
      immunized with rat MAA developed cellular immunity to the antigen. MAA was
      detected only in the iris and CB of the eye. Iris and CB were the major source of
      matrix metalloproteinase-1 (MMP-1) in the naive eye, and ocular expression of MMP
      1 was up-regulated, whereas expression of tissue inhibitor of metalloproteinase 1
      decreased before the onset of EAAU. These results demonstrated that EAAU can be
      induced by autologous MAA. Uveitogenic antigen is present only in the iris and CB
      of the eye, and the imbalance between MMP-1 and tissue inhibitor of
      metalloproteinase 1 may play a role in the generation of MAA in vivo.
      Collectively, the evidence presented here suggests that MAA is an autoantigen in
      EAAU. These observations may extend to idiopathic human anterior uveitis and
      facilitate the development of antigen-specific therapy.

PMID- 19755420
TI  - Exendin-4 promotes liver cell proliferation and enhances the PDX-1-induced liver
      to pancreas transdifferentiation process.
AB  - Over the last few years, evidence has accumulated revealing the unexpected
      potential of committed mammalian cells to convert to a different phenotype via a
      process called transdifferentiation or adult cell reprogramming. These findings
      may have major practical implications because this process may facilitate the
      generation of functional autologous tissues that can be used for replacing
      malfunctioning organs. An instructive role for transcription factors in diverting
      the developmental fate of cells in adult tissues has been demonstrated when adult
      human liver cells were induced to transdifferentiate to the pancreatic endocrine
      lineage upon ectopic expression of the pancreatic master regulator PDX-1
      (pancreatic and duodenal homeobox gene 1). Since organogenesis and lineage
      commitment are affected also by developmental signals generated in response to
      environmental triggers, we have now analyzed whether the hormone GLP-1 (glucogen
      like peptide-1) documented to play a role in pancreatic beta cell
      differentiation, maturation, and survival, can also increase the efficiency of
      liver to pancreas transdifferentiation. We demonstrate that the GLP-1R agonist,
      exendin-4, significantly improves the efficiency of PDX-1-mediated
      transdifferentiation. Exendin-4 affects the transdifferentiation process at two
      distinct steps; it increases the proliferation of liver cells predisposed to
      transdifferentiated in response to PDX-1 and promotes the maturation of
      transdifferentiated cells along the pancreatic lineage. Liver cell reprogramming
      toward the pancreatic beta cell lineage has been suggested as a strategy for
      functional replacement of the ablated insulin-producing cells in diabetics.
      Understanding the cellular and molecular basis of the transdifferentiation
      process will allow us to increase the efficiency of the reprogramming process and
      optimize its therapeutic merit.

PMID- 19755421
TI  - An atypical role for collapsin response mediator protein 2 (CRMP-2) in
      neurotransmitter release via interaction with presynaptic voltage-gated calcium
      channels.
AB  - Collapsin response mediator proteins (CRMPs) specify axon/dendrite fate and
      axonal growth of neurons through protein-protein interactions. Their functions in
      presynaptic biology remain unknown. Here, we identify the presynaptic N-type
      Ca(2+) channel (CaV2.2) as a CRMP-2-interacting protein. CRMP-2 binds directly to
      CaV2.2 in two regions: the channel domain I-II intracellular loop and the distal
      C terminus. Both proteins co-localize within presynaptic sites in hippocampal
      neurons. Overexpression in hippocampal neurons of a CRMP-2 protein fused to
      enhanced green fluorescent protein caused a significant increase in Ca(2+)
      channel current density, whereas lentivirus-mediated CRMP-2 knockdown abolished
      this effect. Interestingly, the increase in Ca(2+) current density was not due to
      a change in channel gating. Rather, cell surface biotinylation studies showed an
      increased number of CaV2.2 at the cell surface in CRMP-2-overexpressing neurons.
      These neurons also exhibited a significant increase in vesicular release in
      response to a depolarizing stimulus. Depolarization of CRMP-2-enhanced green
      fluorescent protein-overexpressing neurons elicited a significant increase in
      release of glutamate compared with control neurons. Toxin block of Ca(2+) entry
      via CaV2.2 abolished this stimulated release. Thus, the CRMP-2-Ca(2+) channel
      interaction represents a novel mechanism for modulation of Ca(2+) influx into
      nerve terminals and, hence, of synaptic strength.

PMID- 19755422
TI  - Different strategies adopted by K(b) and L(d) to generate T cell specificity
      directed against their respective bound peptides.
AB  - Mouse T cell clone 2C recognizes two different major histocompatibility (MHC)
      ligands, the self MHC K(b) and the allogeneic MHC L(d). Two distinct peptides,
      SIY (SIYRYYGL) and QL9 (QLSPFPFDL), act as strong and specific agonists when
      bound to K(b) and L(d), respectively. To explore further the mechanisms involved
      in peptide potency and specificity, here we examined a collection of single amino
      acid peptide variants of SIY and QL9 for 1) T cell activity, 2) binding to their
      respective MHC, and 3) binding to the 2C T cell receptor (TCR) and high affinity
      TCR mutants. Characterization of SIY binding to MHC K(b) revealed significant
      effects of three SIY residues that were clearly embedded within the K(b)
      molecule. In contrast, QL9 binding to MHC L(d) was influenced by the majority of
      peptide side chains, distributed across the entire length of the peptide. Binding
      of the SIY-K(b) complex to the TCR involved three SIY residues that were pointed
      toward the TCR, whereas again the majority of QL9 residues influenced binding of
      TCRs, and thus the QL9 residues had impacts on both L(d) and TCR binding. In
      general, the magnitude of T cell activity mediated by a peptide variant was
      influenced more by peptide binding to MHC than by binding the TCR, especially for
      higher affinity TCRs. Findings with both systems, but QL9-L(d) in particular,
      suggest that many single-residue substitutions, introduced into peptides to
      improve their binding to MHC and thus their vaccine potential, could impair T
      cell reactivity due to their dual impact on TCR binding.

PMID- 19755423
TI  - Elevation of glutamine level by selenophosphate synthetase 1 knockdown induces
      megamitochondrial formation in Drosophila cells.
AB  - Although selenophosphate synthetase 1 (SPS1/SelD) is an essential gene in
      Drosophila, its function has not been determined. To elucidate its intracellular
      role, we targeted the removal of SPS1/SelD mRNA in Drosophila SL2 cells using RNA
      interference technology that led to the formation of vacuole-like globular
      structures. Surprisingly, these structures were identified as megamitochondria,
      and only depolarized mitochondria developed into megamitochondria. The mRNA
      levels of l(2)01810 and glutamine synthetase 1 (GS1) were increased by SPS1/SelD
      knockdown. Blocking the expression of GS1 and l(2)01810 completely inhibited the
      formation of megamitochondria induced by loss of SPS1/SelD activity and decreased
      the intracellular levels of glutamine to those of control cells suggesting that
      the elevated level of glutamine is responsible for megamitochondrial formation.
      Overexpression of GS1 and l(2)01810 had a synergistic effect on the induction of
      megamitochondrial formation and on the synthesis of glutamine suggesting that
      l(2)01810 is involved in glutamine synthesis presumably by activating GS1. Our
      results indicate that, in Drosophila, SPS1/SelD regulates the intracellular
      glutamine by inhibiting GS1 and l(2)01810 expression and that elevated levels of
      glutamine lead to a nutritional stress that provides a signal for
      megamitochondrial formation.

PMID- 19755424
TI  - Evidence that integrin alpha IIb beta 3-dependent interaction of mast cells with
      fibrinogen exacerbates chronic inflammation.
AB  - Integrin alpha IIb beta 3 is expressed in mast cells as well as in
      megakaryocytes/platelets. A recent study has shown that surface expression levels
      of integrin alpha V beta 3 are elevated in integrin alpha IIb-deficient bone
      marrow-derived mast cells (BMMCs) as compared with wild-type (WT) counterparts,
      but the underlying mechanism remains obscure. Here we demonstrate by transducing
      integrin alpha IIb into integrin alpha IIb-deficient BMMCs that surface
      expression levels of integrin alpha V beta 3 are inversely related to those of
      integrin alpha IIb beta 3. Thus, competitive association of integrin beta 3 with
      integrin alpha IIb or integrin alpha V determines surface expression levels of
      integrin alpha IIb beta 3 or alpha V beta 3 in mast cells. We compared WT and
      integrin alpha IIb-deficient BMMCs as well as integrin alpha IIb-deficient BMMCs
      transduced with integrin alpha IIb(WT) or non-functional alpha IIb(D163A) mutant
      and found that enhancement of proliferation, degranulation, cytokine production,
      and migration of BMMCs through interaction with fibrinogen (FB) depended on
      integrin alpha IIb beta 3. In addition, elevated surface expression of integrin
      alpha V beta 3 failed to compensate for loss of FB-associated functions in
      integrin alpha IIb-deficient BMMCs while enhancing adhesion to vitronectin or von
      Willebrand factor. Importantly, integrin alpha IIb deficiency strongly suppressed
      chronic inflammation with the remarkable increase of mast cells induced by
      continuous intraperitoneal administration of FB, although it did not affect acute
      allergic responses or mast cell numbers in tissues in steady states.
      Interestingly, soluble FB promoted cytokine production of BMMCs in response to
      Staphylococcus aureus with FB-binding capacity, through integrin alpha IIb beta 3
      dependent recognition of this pathogen. Collectively, integrin alpha IIb beta 3
      in mast cells plays an important part in FB-associated, chronic inflammation and
      innate immune responses.

PMID- 19755425
TI  - Novel translational control in Arc-dependent long term potentiation consolidation
      in vivo.
AB  - Regulation of translation factor activity plays a major role in protein synthesis
      dependent forms of synaptic plasticity. We examined translational control across
      the critical period of Arc synthesis underlying consolidation of long term
      potentiation (LTP) in the dentate gyrus of intact, anesthetized rats. LTP
      induction by high frequency stimulation (HFS) evoked phosphorylation of the cap
      binding protein eukaryotic initiation factor 4E (eIF4E) and dephosphorylation of
      eIF2alpha on a protracted time course matching the time-window of Arc
      translation. Local infusion of the ERK inhibitor U0126 inhibited LTP maintenance
      and Arc protein expression, blocked changes in eIF4E and eIF2alpha
      phosphorylation state, and prevented initiation complex (eIF4F) formation.
      Surprisingly, inhibition of the mTOR protein complex 1 (mTORC1) with rapamycin
      did not impair LTP maintenance or Arc synthesis nor did it inhibit eIF4F
      formation or phosphorylation of eIF4E. Rapamycin nonetheless blocked mTOR
      signaling to p70 S6 kinase and ribosomal protein S6 and inhibited synthesis of
      components of the translational machinery. Using immunohistochemistry and in situ
      hybridization, we show that Arc protein expression depends on dual, ERK-dependent
      transcription and translation. Arc translation is selectively blocked by
      pharmacological inhibition of mitogen-activated protein kinase-interacting kinase
      (MNK), the kinase coupling ERK to eIF4E phosphorylation. Furthermore, MNK
      signaling was required for eIF4F formation. These results support a dominant role
      for ERK-MNK signaling in control of translational initiation and Arc synthesis
      during LTP consolidation in the dentate gyrus. In contrast, mTORC1 signaling is
      activated but nonessential for Arc synthesis and LTP. The work, thus, identifies
      translational control mechanisms uniquely tuned to Arc-dependent LTP
      consolidation in live rats.

PMID- 19755426
TI  - Spatiotemporal regulation of early lipolytic signaling in adipocytes.
AB  - Hormone-sensitive lipase (HSL) is a key enzyme regulating the acute activation of
      lipolysis. HSL functionality is controlled by multiple phosphorylation events,
      which regulate its association with the surface of lipid droplets (LDs). We
      determined the progression and stability of HSL phosphorylation on individual
      serine residues both spatially and temporally in adipocytes using phospho
      specific antibodies. Within seconds of beta-adrenergic receptor activation, HSL
      was phosphorylated on Ser-660, the phosphorylated form appearing in the
      peripheral cytosol prior to rapid translocation to, and stable association with,
      LDs. In contrast, phosphorylation of HSL on Ser-563 was delayed, the
      phosphorylated protein was predominantly detected on LDs, and mutation of the Ser
      659/Ser-660 site to Ala significantly reduced subsequent phosphorylation on Ser
      563. Phosphorylation of HSL on Ser-565 was observed in control cells; the
      phosphorylated protein was translocated to LDs with similar kinetics to total
      HSL, and the degree of phosphorylation was inversely related to phospho-HSL(Ser
      563). These results describe the remarkably rapid, sequential phosphorylation of
      specific serine residues in HSL at spatially distinct intracellular locales,
      providing new insight into the complex regulation of lipolysis.

PMID- 19755427
TI  - The alphabeta T cell receptor is an anisotropic mechanosensor.
AB  - Thymus-derived lymphocytes protect mammalian hosts against virus- or cancer
      related cellular alterations through immune surveillance, eliminating diseased
      cells. In this process, T cell receptors (TCRs) mediate both recognition and T
      cell activation via their dimeric alphabeta, CD3 epsilon gamma, CD3 epsilon
      delta, and CD3 zeta zeta subunits using an unknown structural mechanism. Here,
      site-specific binding topology of anti-CD3 monoclonal antibodies (mAbs) and
      dynamic TCR quaternary change provide key clues. Agonist mAbs footprint to the
      membrane distal CD3 epsilon lobe that they approach diagonally, adjacent to the
      lever-like C beta FG loop that facilitates antigen (pMHC)-triggered activation.
      In contrast, a non-agonist mAb binds to the cleft between CD3 epsilon and CD3
      gamma in a perpendicular mode and is stimulatory only subsequent to an external
      tangential but not a normal force ( approximately 50 piconewtons) applied via
      optical tweezers. Specific pMHC but not irrelevant pMHC activates a T cell upon
      application of a similar force. These findings suggest that the TCR is an
      anisotropic mechanosensor, converting mechanical energy into a biochemical signal
      upon specific pMHC ligation during immune surveillance. Activating anti-CD3 mAbs
      mimic this force via their intrinsic binding mode. A common TCR quaternary change
      rather than conformational alterations can better facilitate structural signal
      initiation, given the vast array of TCRs and their specific pMHC ligands.

PMID- 19755428
TI  - Heritability of metabolic syndrome traits among healthy younger adults: a
      population based study in China.
AB  - OBJECTIVE To estimate heritability of metabolic syndrome traits among healthy
      younger adults in a human population in China, and examine potential sex
      differences in heritability and parental effect on metabolic syndrome traits.
      METHODS Using offspring-parent regression, we estimated heritability (h(2)) of
      metabolic syndrome traits based on 452 child-parent triads identified from a
      population based random survey on metabolic syndrome among people over 15 years
      of age in Guangzhou, China. RESULTS Body mass index (BMI), cholesterol, high
      density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL
      C), fasting plasma glucose (FPG) and waist circumference (waist-C) were more
      heritable (h(2), 0.42-0.545), whereas systolic blood pressure (SBP), diastolic
      blood pressure (DBP), and triglycerides (TG) were less heritable (h(2), 0.14
      0.28). Sons had pronounced increases in heritability for all traits over
      daughters, particularly for cholesterol (0.653 vs 0.356), FPG (0.602 vs 0.313),
      LDL-C (0.521 vs 0.329), and TG (0.395 vs 0.187). Offspring-mother seemed to have
      a higher heritability in every trait except FPG (0.67 vs 0.794) than offspring
      father, most notably for DBP (0.308 vs 0.122), SBP (0.288 vs 0.146), TG (0.387 vs
      0.239) and waist-C (0.581 vs 0.354). CONCLUSION We estimated the heritability of
      metabolic syndrome traits in a human population based on a unique population
      based offspring-parent sample from China, and found important evidence that the
      maternal and paternal effects on these traits are different and the sex
      difference in heritability is pronounced.

PMID- 19755429
TI  - Phenotypic spectrum associated with de novo and inherited deletions and
      duplications at 16p11.2 in individuals ascertained for diagnosis of autism
      spectrum disorder.
AB  - BACKGROUND: Recurrent microdeletions and microduplications of approximately 555
      kb at 16p11.2 confer susceptibility to autism spectrum disorder (ASD) in up to 1%
      of ASD patients. No physical or behavioural features have been identified that
      distinguish these individuals as having a distinct ASD subtype, but clinical data
      are limited. METHODS: We report five autistic probands identified by microarray
      analysis with copy number variation (CNV) of 16p11.2 (three deletions, two
      duplications). Each patient was assessed for ASD and dysmorphic features. We also
      describe a deletion positive 26-month-old female who has developmental delay (DD)
      and autistic features. RESULTS: Proband 1 (female with ASD, de novo deletion) is
      not dysmorphic. Proband 2 (male with autism, de novo deletion) and proband 3 and
      his brother (males with autism, inherited deletions) are dysmorphic, but the two
      probands do not resemble one another. The mother of proband 3 has mild mental
      retardation (MR), minor dysmorphism and meets the criteria for ASD. Proband 4
      (dysmorphic autistic male, de novo duplication) had a congenital diaphragmatic
      hernia. Proband 5 (non-dysmorphic ASD female with a duplication) has two
      apparently healthy duplication positive relatives. Probands 1 and 2 have deletion
      negative siblings with ASD and Asperger syndrome, respectively. Proband 6 (a
      female with DD and an inherited duplication) is dysmorphic, but has
      oligohydramnios sequence. CONCLUSIONS: The phenotypic spectrum associated with
      CNV at 16p11.2 includes ASD, MR/DD and/or possibly other primary psychiatric
      disorders. Compared with the microduplications, the reciprocal microdeletions are
      more likely to be penetrant and to be associated with non-specific major or minor
      dysmorphism. There are deletion positive ASD probands with a less severe
      phenotype than deletion negative ASD siblings underscoring the significant
      phenotypic heterogeneity.

PMID- 19755430
TI  - Can our understanding of epigenetics assist with primary prevention of congenital
      defects?
AB  - Having identified teratogenic factors, primary prevention of congenital defects
      is possible by the implementation of specific measures in pregnant women or those
      planning pregnancy. Our current understanding of the epigenetic processes acting
      during reproductive events raises new possibilities to prevent both heritable and
      sporadic congenital anomalies. Cell differentiation during embryonic-fetal
      development involves different epigenetic processes which, if altered, may affect
      either somatic or germ cells. Epigenetic alterations can occur in somatic cells
      at different stages of life, from fecundation to adulthood, and when germ cells
      are affected, such changes can even be passed on to future generations. This
      review summarises the main epigenetic processes that influence gene expression
      and cell specification at different stages of development. The experimental and
      epidemiological evidence of environmental agents that cause epigenetic
      alterations is evaluated, as well as their effects in males and females. As a
      result, new avenues for primary prevention are proposed.

PMID- 19755431
TI  - Scalp fibroblasts have a shared expression profile in monogenic craniosynostosis.
AB  - BACKGROUND: Craniosynostosis can be caused by both genetic and environmental
      factors, the relative contributions of which vary between patients. Genetic
      testing identifies a pathogenic mutation or chromosomal abnormality in ~ 21% of
      cases, but it is likely that further causative mutations remain to be discovered.
      OBJECTIVE: To identify a shared signature of genetically determined
      craniosynostosis by comparing the expression patterns in three monogenic
      syndromes with a control group of patients with non-syndromic sagittal
      synostosis. METHODS: Fibroblasts from 10 individuals each with Apert syndrome
      (FGFR2 substitution S252W), Muenke syndrome (FGFR3 substitution P250R), Saethre
      Chotzen syndrome (various mutations in TWIST1) and non-syndromic sagittal
      synostosis (no mutation detected) were cultured. The relative expression of ~
      47,000 transcripts was quantified on Affymetrix arrays. RESULTS: 435, 45 and 46
      transcripts were identified in the Apert, Muenke and Saethre-Chotzen groups,
      respectively, that differed significantly from the controls. Forty-six of these
      transcripts were shared between two or more syndromes and, in all but one
      instance, showed the same direction of altered expression level compared with
      controls. Pathway analysis showed over-representation of the shared transcripts
      in core modules involving cell-to-cell communication and signal transduction.
      Individual samples from the Apert syndrome cases could be reliably distinguished
      from non-syndromic samples based on the gene expression profile, but this was not
      possible for samples from patients with Muenke and Saethre-Chotzen syndromes.
      CONCLUSIONS: Common modules of altered gene expression shared by genetically
      distinct forms of craniosynostosis were identified. Although the expression
      profiles cannot currently be used to classify individual patients, this may be
      overcome by using more sensitive assays and sampling additional tissues.

PMID- 19755432
TI  - Development of an algorithm for evaluating personal doses due to photon fields in
      terms of operational quantities for TLD badge system in India.
AB  - In order to evaluate and report the personal doses in terms of personal dose
      equivalent, the performance of the CaSO(4):Dy based thermoluminescence dosemeter
      (TLD) badge used for countrywide personnel monitoring in India is investigated
      using monoenergetic and narrow spectrum radiation qualities equivalent to those
      given in ISO standards. Algorithms suitable for evaluating H(p)(10) and
      H(p)(0.07) within +/- 30 % are developed from the responses of dosemeter
      elements/discs under different filters for normal as well as angular irradiation
      conditions using these beams. The algorithm is tested for TLD badges irradiated
      to mixtures of low- and high-energy ((137)Cs) beams in various proportions. The
      paper concludes with the results of test of algorithm by evaluation of badges
      used in the IAEA/RCA intercomparison studies and discussion on inherent
      limitations.

PMID- 19755433
TI  - Secondary charged particle equilibrium in 137Cs and 60Co reference radiation
      fields.
AB  - During the calibration or irradiation of dosemeters, typical irradiation
      geometries (collimated beams) and source-to-detector distances (1-5 m) lead to
      the fact that for photon energies above a few hundred keV, the secondary charged
      particle equilibrium is usually not ensured. The reason is that the effective
      beam radius at the detector position is smaller than the range of the secondary
      electrons produced in air whose maximum particle energy is as large as the
      maximum photon energy. Therefore, the International Organization for
      Standardization (ISO) recommends putting a build-up plate (BUP) made of
      polymethyl methacrylate in front of the dosemeter to be calibrated in ISO 4037-3.
      In this paper, the effect of the thickness of the BUP and its distance from the
      dosemeter at different source-to-dosemeter distances were investigated by means
      of measurement and calculation. It turned out that the geometrical arrangement of
      the source, dosemeter and BUP recommended by ISO mostly does not ensure secondary
      charged particle equilibrium. The consequence is to always place the BUP directly
      in front of the dosemeter to be calibrated or irradiated.

PMID- 19755434
TI  - Occupational exposure to ambient electromagnetic fields of technical operational
      personnel working for a mobile telephone operator.
AB  - In order to investigate the exposure of operational personnel to radiofrequency
      electromagnetic fields when working for a mobile telephone operator, exposimeters
      were used to make individual records on 23 Technical Operations personnel (mobile
      telephone maintenance staff) and also on 22 Other Workers. The exposure
      densities, to which each of the 45 subjects was subjected, were quantified using
      229 exposure indicators. Cluster analysis techniques were applied to the data, in
      an attempt to show that they would re-emerge as belonging to one of the two
      groups, i.e. the Technical Operational Personnel group or the Other Workers
      group. This exploratory investigation has shown that the cluster analysis does
      not reveal a sufficiently reliable emergence of the two groups, even though
      certain exposure indicators were significantly different for the two groups. In
      addition, the use of a Learning Group method does not lead to the discovery of a
      predictive law that could identify the Technical Operational Personnel as a sub
      group within the overall group.

PMID- 19755435
TI  - Safety of a novel galacto-oligosaccharide: Genotoxicity and repeated oral dose
      studies.
AB  - A series of safety tests were undertaken on a novel galacto-oligosaccharide (GOS)
      produced from lactose by a two-step enzymatic process involving Sporobolomyces
      singularis and Kluyveromyces lactis. Bacterial reverse mutation and chromosomal
      aberration tests, with or without metabolic activation, were performed. These
      tests showed no mutagenesis in the Ames assay or in Escherichia coli WP2uvrA, and
      no chromosomal aberrations in cultured fibroblast cells from Chinese hamster
      lungs (CHL/IU). Micronuclei were not induced in the reticulocytes of mouse
      peripheral blood following oral administration of GOS. In a 90-day repeated oral
      dose toxicity study in rats, GOS was administered at 0, 500, 1000 and 2000 mg/kg
      to male and female Sprague-Dawley rats. There were no GOS-related changes in
      clinical signs, body weight, water intake, feed intake, urinalysis,
      ophthalmology, haematology, blood chemistry, organ weights, gross pathology or
      histopathology in any of the treatment groups compared to the control group. The
      no observed adverse effect level (NOAEL) of GOS was at least 2000 mg/kg/day in
      both males and females.

PMID- 19755436
TI  - Studies on hypoglycaemic effects of polyherbal preparation in streptozotocin
      induced diabetic male albino rats.
AB  - Many traditional treatments have been recommended in the alternative system of
      medicine for diabetes mellitus. However, the mode of action of most of the
      herbals used has not been defined. It has been reported that sex hormones are
      important regulators of insulin-mediated events in skeletal muscles. In view of
      this, a novel herbal preparation containing antidiabetic and aphrodisiac plants
      was used in the present study. Adult male albino rats were divided into following
      groups after induction of diabetes. Rats were given an intraperitoneal (i.p.)
      injection of streptozotocin (STZ), at a dose of 65 mg/kg body weight after
      overnight fasting, to induce diabetic state with blood glucose levels >250 mg/dL.
      Group 1-Control rats treated with single i.p. injection of vehicle, Group 2-Rats
      treated with polyherbal preparation (PHP; 500 mg/kg body weight by oral
      intubation, morning and evening for 30 days), Group 3-STZ-diabetic rats treated
      orally with equal volumes of vehicle (water) alone and Group 4-STZ-diabetic rats
      treated with PHP after 10 days of diabetic induction. STZ-diabetes decreased the
      body weight, serum insulin level and glucose oxidation in liver and skeletal
      muscles but increased the fasting blood glucose level. After polyherbal
      treatment, body weight and glucose oxidation were completely restored to control
      level while serum insulin level was restored partially and the glucose tolerance
      was significantly improved. There was a significant decrease in total haemoglobin
      (Hb) level of diabetic rats when compared to control but polyherbal treatment
      significantly improved the same. However, the other parameters studied (red blood
      cell [RBC], white blood corpuscle [WBC], packed cell volume [PCV], mean
      corpuscular volume [MCV] and mean corpuscular haemoglobin [MCH]) were unaltered.
      In conclusion, the anti-diabetic properties of PHP appear to be mediated through
      pancreatic beta-cell regeneration, resulting in maintenance of optimal blood
      glucose and its oxidation in liver and skeletal muscles.

PMID- 19755437
TI  - Use of pralidoxime without atropine in rivastigmine (carbamate) toxicity.
AB  - Some experimental models suggest that the use of pralidoxime in carbamate
      toxicity is deleterious. Although pretreatment with atropine minimizes the
      adverse effect of pralidoxime reported in these models, concerns over the risks
      of pralidoxime in humans with carbamate poisoning continue. We present a unique
      case of carbamate toxicity treated successfully with pralidoxime alone. An 80
      year-old woman with Alzheimer's dementia presented to the emergency department
      with 3-4 days of lightheadedness, vomiting, diarrhea, and bilateral lower
      extremity muscle pain. Extensive review of systems was otherwise negative. Her
      vital signs were BP, 207/85 mmHg; pulse, 101 beats/min; rectal temperature, 36.6(
      degrees )C; respirations, 18/min; and SpO(2), 95% breathing room air. Her bedside
      glucose measurement was 6.7 mmol/L. Physical examination revealed a confused,
      diaphoretic, ill-appearing woman with miosis and fasciculations of the tongue,
      eyelids, gastrocnemius and quadriceps bilaterally. The heart, lung, abdominal and
      head, eyes, ears, nose and throat examinations were otherwise unremarkable. Nine
      5-cm(2) rivastigmine patches (9.5 mg/24-hour) were found adherent to her torso
      and lower extremities. The patches were immediately removed and underlying skin
      cleansed with soap and water. Laboratory values including complete blood count,
      basic metabolic panel, calcium, magnesium, phosphorus, troponin, coagulation
      studies and urinalysis were unremarkable. Due to the absence of pulmonary
      muscarinic findings, no atropine was administered. However, 1 g of pralidoxime
      was administered intravenously over 30 min to treat fasciculations. Within 30 min
      of this treatment, there was significant improvement in symptoms and resolution
      of fasciculations. She was admitted to the hospital, required no further
      pralidoxime therapy and was discharged after 3 days. Rivastigmine is a reversible
      (carbamate) cholinesterase inhibitor used to treat dementia. In overdose,
      cholinergic crisis is expected and in this case was precipitated by patch
      overuse. We believe there was a causal relationship between pralidoxime
      administration and the prompt resolution of symptoms and fasciculations. This
      case of apparently safe and effective pralidoxime use without concomitant
      atropine administration in a patient with carbamate toxicity reinforces recent
      data demonstrating the potential safety of pralidoxime in carbamate toxicity.

PMID- 19755438
TI  - Mode of cellular toxicity of aqueous extract of Fadogia agrestis (Schweinf. Ex
      Hiern) stem in male rat liver and kidney.
AB  - The mode of cellular toxicity of aqueous extract of Fadogia agrestis stem in male
      rats was investigated. Rats were grouped into four: A, B, C and D where A (the
      control) received orally 1 mL of distilled water; B, C and D (test groups)
      received orally 18, 50 and 100 mg/kg body weight of the extract, respectively,
      for 28 days. Infrared spectroscopy indicated the presence of hydroxyl (OH) and
      primary amine (CONH). Clinical toxicity symptoms such as respiratory distress,
      epistasis, salivation, hypo- and hyperactivity were not observed at any period of
      the experiment. No mortality was also recorded. Extract administration
      significantly reduced (p < .05) the activities of alkaline phosphatase, lactate
      dehydrogenase and gamma glutamyl transferase in the liver and kidney with
      corresponding increases in the serum. Serum malondialdehyde also increased
      significantly in all the extract-treated groups. The liver and kidney body weight
      ratios of the extract-treated animals compared well (P > .05) with their controls
      throughout the experimental period. The extract did not cause any swelling,
      atrophy or hypertrophy of the organs. The other evidence in this study suggests
      disruption of the ordered lipid bilayer of the plasma membranes of the
      hepatocytes and nephrons. This might have resulted from peroxidation of the
      polyunsaturated fatty acids on the membranes of the hepatocytes and nephrons made
      possible by the functional groups or the product of metabolism of the extract.
      This may be responsible for the compromise of the integrity of the plasma
      membranes of the hepatocytes and nephrons.

PMID- 19755439
TI  - Toxicological implications of aqueous extract of Bambusa vulgaris leaves in
      pregnant Dutch rabbits.
AB  - Aqueous extract of Bambusa vulgaris L. leaves at 250 and 500 mg/kg body weight
      was investigated for toxic effects in pregnant rabbits. Apparently healthy,
      female rabbits (Dutch) weighing between 1.62 and 1.70 kg as previously used in
      our abortifacient study were paired overnight with male rabbits in ratio 2:1 and
      those that became pregnant were completely randomized into three groups (A-C).
      Group A (the control), received orally 1.85 mL/kg body weight (3 mL) of distilled
      water thrice daily on days 1-9 of pregnancy while groups B and C were treated
      orally with the same volume corresponding to 250 and 500 mg/kg body weight of the
      extract. Clinical signs of toxicity were not observed in all the animals during
      the study. The extract did not significantly alter (p > .05) the serum follicle
      stimulating hormone and total protein content of the pregnant rabbits throughout
      the exposure period whereas, the concentrations of luteinizing hormone,
      progesterone, albumin, globulin, urea and calcium decreased in the serum of the
      rabbits. At 250 mg/kg body weight, the extract increased kidney alkaline
      phosphatase (ALP) activity whereas at 500 mg/kg body weight of the extract, the
      ALP level was similar to the control group. Liver ALP at all doses, as well as
      the activity of gamma glutamyl transferase (GGT) at 500 mg/kg body weight was
      reduced. This reduction was accompanied by an increase in serum ALP and GGT at
      these doses. At 250 mg/kg, the extract increased kidney GGT. Conversely, at 500
      mg/ kg, kidney GGT activity decreased. Liver and serum GGT were not altered by
      the 250 mg/kg. The extract also increased the serum levels of creatinine, uric
      acid, sodium, potassium and bicarbonate ions as well as total and conjugated
      bilirubin. In the hepatocytes of extract-treated animals, there was no evidence
      of necrosis, inflammation, fibrosis and degenerative changes in the central vein
      and radiating hepatic cords, while the glomerulus and the tubules of the nephrons
      also remained intact. The alterations in biochemical parameters by the aqueous
      extract of B. vulgaris leaves suggests adverse effect on the synthetic,
      secretory, reabsorptive and excretory functions of liver and kidney of the
      animals. Therefore, the absence of histopathological lesions in the hepatocytes
      and nephrons implies that histopathological changes are not a sensitive assay for
      the assessment of tissue damage by the extract.

PMID- 19755440
TI  - Time-dependent changes in lead and delta-aminolevulinic acid after subchronic
      lead exposure in rats.
AB  - The time-dependent changes in lead (Pb) concentrations in major tissues, serum
      and urine, and the Pb biomarker delta-aminolevulinic acid (ALA) concentration in
      urine were studied in rats after sub-chronic Pb exposure. Female Sprague-Dawley
      (SD) rats were exposed to Pb in drinking water at concentrations of 100 ppm and
      1000 ppm for 30 days. The Pb concentration in muscle, liver, kidney, plasma and
      urine, and the ALA concentration in urine were determined during exposure and
      every 7 days after exposure for 3 weeks. The muscle Pb concentration did not
      change post exposure. The liver Pb concentration increased 2.2 to 2.8 times (100
      ppm group) and 3.9 to 7.4 times (1000 ppm group) during exposure, then decreased
      rapidly. Kidney Pb concentrations were 8.0 to 14.3 times (100 ppm group) and 13.8
      to 28.5 times (1000 ppm group) higher than controls during exposure and decreased
      for 1 to 2 weeks post exposure. Plasma Pb concentrations were 1.2 to 3.3 times
      (100 ppm group) and 2.9 to 5.8 times (1000 ppm group) higher than control
      concentrations during exposure and decreased time-dependently in the 1000-ppm
      group after exposure. Urine Pb concentrations were 8.5 to 10.7 times (100 ppm
      group) and 30.4 to 51.1 times (1000 ppm group) higher than control concentrations
      during exposure and rapidly decreased after exposure, though concentrations
      remained up to 4 times higher than controls in the 1000 ppm exposure group. Urine
      ALA concentrations increased 1.7 to 2.6 and 7.1 to 32.7 times during exposure in
      the 100 ppm and 1000 ppm groups respectively, and remained elevated for 21 days
      post exposure. Our data support that urine Pb concentration is a useful marker
      for acute Pb exposure or post exposure. Urine ALA may be a predicator of
      biological response to Pb exposure.

PMID- 19755441
TI  - Quercetin-induced apoptosis acts through mitochondrial- and caspase-3-dependent
      pathways in human breast cancer MDA-MB-231 cells.
AB  - There has been considerable evidence recently demonstrating the anti-tumour
      effects of flavonols. Quercetin, an ubiquitous bioactive flavonol, inhibits cells
      proliferation, induces cell cycle arrest and apoptosis in different cancer cell
      types. The precise molecular mechanism of quercetin-induced apoptosis in human
      breast cancer cells is unclear. The purpose of this study was to investigate
      effects of quercetin on cell viability and to determine its underlying mechanism
      in human breast cancer MDA-MB-231 cells. Quercetin decreased the percentage of
      viable cells in a dose- and time-dependent manner, which was associated with cell
      cycle arrest and apoptosis. Quercetin did not increase reactive oxygen species
      generation but increased cytosolic Ca(2+) levels and reduced the mitochondrial
      membrane potential (DeltaPsi(m)). Quercetin treatment promoted activation of
      caspase-3, -8 and -9 in MDA-MB-231 cells. Caspase inhibitors prevented the
      quercetin-induced loss of cell viability. Quercetin increased abundance of the
      pro-apoptotic protein Bax and decreased the levels of anti-apoptotic protein Bcl
      2. Confocal laser microscope examination indicated that quercetin promoted
      apoptosis-inducing factor (AIF) release from mitochondria and stimulated
      translocation to the nucleus. Taken together, these findings suggest that
      quercetin results in human breast cancer MDA-MB-231 cell death through
      mitochondrial- and caspase-3-dependent pathways.

PMID- 19755442
TI  - Safety of engineered nanomaterials and emerging nanotechnologies--do we know
      enough to allow us to make reliable judgments?

PMID- 19755443
TI  - Cross-sectional study on respiratory effect of toner exposure.
AB  - In this baseline study, part of a cohort study to clarify the effect of toner
      exposure on the respiratory system, we surveyed 803 male toner workers and 802
      referents with regard to their subjective respiratory symptoms and chest X-ray
      results. We also examined individual exposure history, current working
      conditions, and personal exposure levels to toner. There was a significantly
      higher prevalence of "coughing and sputum" related complaints among toner-exposed
      workers in the 30 and 40-year age groups. The group with toner-exposure history
      showed a higher odds ratio, by logistic regression, in relation to all questions
      regarding coughing. Mild fibrotic changes were observed in the chest X-rays of
      four workers who had engaged in toner-exposure work for at least a decade or
      more, and all four had reported allergic disease. Although we observed a tendency
      of higher prevalence of "coughing and sputum" in toner-exposed workers, the
      possibility of information bias cannot be eliminated. It should also be noted
      that this tendency did not exceed that of the general public. Further analysis is
      required in this ongoing 10-year cohort study to clarify the effect of toner
      exposure on the respiratory system.

PMID- 19755444
TI  - Cross-sectional study on respiratory effect of toner-exposed work in
      manufacturing plants, Japan: pulmonary function, blood cells, and biochemical
      markers.
AB  - The aim of the study is to examine the relationship between toner-exposed work
      and health indices related to respiratory disorders and to confirm the baseline
      of a cohort study to clarify the effect of toner exposure in manufacturing
      plants. Subjects were 1614 male workers (809 toner-exposed workers and 805
      referents) who were engaged in toner manufacturing plants in Japan (Fuji Xerox
      Co., Ltd). The age of subjects was from 19 to 59 years, and the average age was
      40.2 years(median 40 years, SD 7.67). We conducted a pulmonary function test
      (PEFR, VC, FVC, FEV(1.0)%, V25/Ht) and a blood cell test (RBC, Hb, Hct, Plt, WBC,
      cell contents of WBC) and measured biochemical indices in blood (ALT, AST, gamma
      GTP, CRP, IgE) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in urine. Student t-test
      and logistic regression analysis were applied to compare between the toner
      exposed workers and the referents and to analyze the relationship among indices
      of effects and independent factors. There was no significant difference between
      the two groups in blood cell count and biochemical indices. Inflammation- and
      allergy-related markers such as 8OHdG and IgE also showed no significant
      difference between toner-exposed workers and the referents. The influence of
      smoking on pulmonary function indices was observed, but there was no relationship
      between the pulmonary function and toner-exposed work. In this article, we report
      a preliminary cross-sectional analysis in the subjects of a cohort study. No
      difference in pulmonary function indices was observed between the toner-exposed
      workers and the referents, and there was no consistent relationship between the
      exposure status and examined indices; however, the prevalence of subjective
      respiratory symptoms was higher in the exposed workers as presented in another
      report. Further analysis is important in the ongoing cohort study to clarify the
      effect of toner exposure on respiratory systems.

PMID- 19755445
TI  - Genotoxic effects of nanosized and fine TiO2.
AB  - The in-vitro genotoxicity of nanosized TiO(2) rutile and anatase was assessed in
      comparison with fine TiO(2) rutile in human bronchial epithelial BEAS 2B cells
      using the single-cell gel electrophoresis (comet) assay and the cytokinesis-block
      micronucleus test. BEAS 2B cells were exposed to eight doses (1-100 microg/cm(2))
      of titanium(IV) oxide nanosized rutile (>95%, <5% amorphous SiO(2) coating; 10 x
      40 nm), nanosized anatase (99.7%; <25 nm), or fine rutile (99.9%; <5 microm) for
      24, 48, and 72 h. Fine rutile reduced cell viability at lower doses than
      nanosized anatase, which was more cytotoxic than nanosized rutile. In the comet
      assay, nanosized anatase and fine rutile induced DNA damage at several doses with
      all treatment times. Dose-dependent effects were seen after the 48- and 72-h
      treatments with nanosized anatase and after the 24-, 48- (in one out of two
      experiments), and 72-h treatments (one experiment) with fine rutile. The lowest
      doses inducing DNA damage were 1 microg/cm(2) for fine rutile and 10 microg/cm(
      2) for nanosized anatase. Nanosized rutile showed a significant induction in DNA
      damage only at 80 microg/cm(2) in the 24-h treatment and at 80 and 100 microg/
      cm(2) in the 72-h treatment (with a dose-dependent effect). Only nanosized
      anatase could elevate the frequency of micronucleated BEAS 2B cells, producing a
      significant increase at 10 and 60 microg/cm( 2) after the 72-h treatment (no dose
      dependency). At increasing doses of all the particles, MN analysis became
      difficult due to the presence of TiO(2) on the microscopic slides. In conclusion,
      our studies in human bronchial epithelial BEAS 2B cells showed that uncoated
      nanosized anatase TiO(2) and fine rutile TiO(2) are more efficient than SiO( 2)
      coated nanosized rutile TiO(2) in inducing DNA damage, whereas only nanosized
      anatase is able to slightly induce micronuclei.

PMID- 19755446
TI  - Experimental evaluation of personal protection devices against graphite
      nanoaerosols: fibrous filter media, masks, protective clothing, and gloves.
AB  - In this study, different conventional personal protection devices (fibrous
      filters, cartridges for respirators, protective clothing, and gloves) well
      qualified for micron particles were tested with graphite nanoparticles ranging
      from 10 to 100 nm (electrical mobility diameter). For this purpose, two specific
      test benches were designed: one for filter-based devices which are tested under a
      controlled air flow and other for gloves and protective clothing based on the
      "through diffusion method." The penetration versus particle size shows for most
      tested filter media the behavior predicted by the theoretical Brownian capture:
      penetration decreases when particle diameter decreases. No thermal rebound was
      detected until 10 nm for graphite nanoparticles. Protective clothes were tested
      by two methods and same trends were obtained. Nonwoven fabrics (air-tight
      materials) are much more efficient against nanoparticles than cotton and paper.
      Gloves tested by "through diffusion technique," in static condition seem to
      efficiently protect against graphite nanoparticles in spite of their important
      porosity.

PMID- 19755447
TI  - Airway barrier dysfunction induced by exposure to carbon nanotubes in vitro:
      which role for fiber length?
AB  - Although carbon nanotubes (CNTs) are increasingly used, their biological effects
      are only incompletely characterized. However, experimental evidence suggests that
      the intratracheal instillation of CNTs causes the formation of interstitial
      granulomas and progressive pulmonary fibrosis in rodents. Using human epithelial
      Calu-3 cells as a model of airway epithelium in vitro, we have recently reported
      that the exposure to commercial multi-walled CNTs (MWCNTs) causes a progressive
      decrease of the transepithelial electrical resistance (TEER), pointing to a CNT
      dependent impairment of the epithelial barrier function. To characterize better
      this behavior, we compared the effects of two types of MWCNTs and single-walled
      CNTs (SWCNTs) of different lengths on the TEER of Calu-3 monolayers. All the
      materials were used at a dose of 100 microg/mL corresponding to an exposure of 73
      microg/cm(2) of cell monolayer. Only the longer MWCNTs and SWCNTs cause a
      significant decrease in TEER. To elucidate the mechanism underlying the changes
      in barrier function, the expression of the junction proteins occludin and ZO-1
      has been also assessed. No significant decrease in the mRNA for either protein is
      detectable after the exposure to any type of CNTs. It is concluded that the
      impairment of barrier function in Calu-3 monolayers is a peculiar effect of CNTs
      endowed with clear cut fiber properties and is not referable to marked changes in
      the expression of junction proteins.

PMID- 19755448
TI  - Cardiac autonomic regulation after lung exposure to carbon nanotubes.
AB  - The ultrafine (UF) component of airborne pollution may impair cardiovascular
      autonomic control, a high-risk condition for cardiovascular adverse events. Since
      engineered nanoparticles, such as single-walled carbon nanotubes (SWCNTs) share
      physicochemical properties with UF, they might have similar adverse effects. Aim
      of the study was to evaluate arterial baroreflex function (BRF) at baseline, 24 h
      after the first instillation, immediately before the second one, and 2 weeks
      later, in adult Wystar-Kyoto conscious rats undergoing two intratracheal
      instillations of SWCNT (eight rats) or phosphate buffer saline (PBS) (five rats)
      at 2-week interval. During each session, 30-min continuous recording of arterial
      pressure and pulse interval was performed by a telemetered catheter implanted in
      the abdominal aorta of the rats. BRF was studied by the sequence technique.
      SWCNTs dispersed in PBS (1 mg/ml) were administered immediately after sonication
      (1 microg/g body weight). A significant decrease in the number of baroreflex
      sequences (from 498 +/- 27.1 at baseline to 287 +/- 40.2 at the recording
      performed after 4 weeks; P < 0.05) was observed in SWCNT-instilled rats, whereas
      no significant change was detected in controls. These data suggest that SWCNTs
      may alter the BRF, thus affecting the autonomic cardiovascular control
      regulation.

PMID- 19755449
TI  - Preparation of nanoparticle dispersions for in-vitro toxicity testing.
AB  - Studies on potential toxicity of engineered nanoparticle (ENP) in biological
      systems require a proper and accurate particle characterization to ensure the
      reproducibility of the results and to understand biological effects of ENP. A
      full characterization of ENP should include various measurements such as particle
      size and size distribution, shape and morphology, crystallinity, composition,
      surface chemistry, and surface area of ENP. It is also important to characterize
      the state of ENP dispersions. In this study, four different ENPs, rutile and
      anatase titanium dioxides and short single- and multi-walled carbon nanotubes,
      were characterized in two dispersion media: bronchial epithelial growth medium,
      used for bronchial epithelial BEAS cells, and RPMI-1640 culture media with 10% of
      fetal calf serum (FCS) for human mesothelial (MeT-5A) cells. The purpose of this
      study was to determine the characteristics of ENPs and their dispersions as well
      as to compare dispersion additives suitable for toxicity tests and thus establish
      an appropriate way to prepare dispersions that performs well with the selected
      ENP. Dispersion additives studied in the media were bovine serum albumin (BSA) as
      a protein resource, dipalmitoyl phosphatidylcholine (DPPC) as a model lung
      surfactant, and combination of BSA and DPPC. Dispersions were characterized using
      optical microscopy and transmission electron microscopy. Our results showed that
      protein addition, BSA or FCS, in cell culture media generated small agglomerates
      of primary particles with narrow size variations and improved the stability of
      the dispersions and thus also the relevance of the in-vitro genotoxicity tests to
      be done.

PMID- 19755450
TI  - Safety assessment of azelaic acid and its derivatives entrapped in nanovesicles.
AB  - The aim of this study was to determine the safety of azelaic acid (AA) and its
      derivatives in nanovesicles for pharmaceutical and cosmetic uses. The hydrophilic
      property of AA was modified by complexing AA with hydroxypropyl-beta-cyclodextrin
      (AACD). The lipophilic property of AA was improved to diethyl azelate (DA) by
      esterification with Fischer reaction. AA, AACD and DA were entrapped in liposomes
      and niosomes with the compositions of L-alpha-dipalmitoyl
      phosphatidylcholine/cholesterol = 7:3 and Tween 61/cholesterol = 1:1,
      respectively, by chloroform film method with sonication. The size of the vesicles
      ranged from 50 to 200 nm, indicating nanosize characteristics. The cytotoxicity
      of AA, AACD and DA entrapped nanovesicular formulations on mouse epidermal cell
      lines (JB6, normal cell lines) by the sulforhodamine B assay was modest when
      compared with cisplatin. Blank liposomes and niosomes gave no growth inhibitory
      effect. The irritation of AA, AACD and DA entrapped and not entrapped in
      nanovesicles on rabbit skin was examined according to the Environmental
      Protection Agency health effect test guidelines. The results showed no signs of
      erythema or edema within 72 h. AA and its derivatives were safe for topical use
      when entrapped in nanovesicles because of no toxicity to normal cell lines and no
      allergy on rabbit skin.

PMID- 19755451
TI  - A nanobiological approach to nanotoxicology.
AB  - There is an urgent need to develop efficient and rapid strategies in order to
      characterize the potential health risks associated with nanomaterials, given the
      speed with which applications and uses are increasing. Use of standard toxicity
      methods will not be sufficient to meet this need. This article proposes the
      adoption of two novel guidances: the system's biological approach to toxicity
      testing advocated by the US National Research Council and a nanobiological
      perspective that identifies key events at the nanoscale that are relevant to
      signal transduction and structural biology.

PMID- 19755452
TI  - Risk assessment model of occupational exposure to nanomaterials.
AB  - Recent development of nanotechnology allows precise assessment of the risks
      workers are exposed to. To assess the risks, a specific risk assessment model has
      been developed with reference to workplaces where nanoparticles are present. This
      model allows identification and quantification of the health hazards for workers.
      The use of nanomaterials presents some uncertainties regarding effective level of
      danger, and risk assessment takes this into consideration with the help of an
      appropriate index. An evaluation algorithm considers both normal work conditions
      and abnormal/emergency situations. Evaluation outcome consists of several risk
      levels with several subdivisions. For each single level, it is possible to
      develop specific behavioral guidelines. The present evaluation model has been
      implemented in research laboratories. The results are middle to high-level risks.

PMID- 19755453
TI  - Guidance for handling and use of nanomaterials at the workplace.
AB  - Chances and risks of nanomaterials is a most fascinating challenge of future
      technologies. This new technology and their related materials are beneficial, for
      example, for energy reduction, lower emissions to the environment, and safe
      resources. However, there are concerns about health effects related to the very
      small dimensions of such materials. Because of our commitment to the principles
      of "Sustainable Chemistry" and "Responsible Care(R)," the chemical industry
      actively cooperates with all relevant stakeholders to assure a safe handling and
      use of nanomaterials. In this manner, the German chemical industry is committed
      to establish and disseminate best practices for a responsible production and use
      of nanomaterials. Protection of human life and the environment is a fundamental
      principle for our industry. Even though in the European Union the existing legal
      framework for risk assessment for chemical substances applies for nanomaterials,
      specific properties of nanomaterials may require amendments. The German Chemical
      Industry Association (Verband der Chemischen Industrie, VCI) has, therefore,
      issued guidance documents and recommendation papers to support companies in the
      sustainable and responsible development of nanotechnology-based applications. One
      of these guidance documents focused on ensuring the workplace safety of our
      employees. Background for this document was a joint survey on occupational health
      and safety in the handling and use of nanomaterials, which was conducted in
      spring 2006 from the German Federal Institute for Occupational Safety and Health
      (Bundesanstalt fur Arbeitsschutz und Arbeitsmedizin, BAuA) and VCI. The purpose
      of the survey was to obtain an overview of occupational health and safety methods
      currently applied in the chemical industry in activities involving nanomaterials.
      The questionnaire survey was evaluated by BAuA; the "Guidance for Handling and
      Use of Nanomaterials at the Workplace" was elaborated predominantly by VCI. This
      Guidance provides some orientation regarding measures in the production and use
      of nanomaterials at the workplace. The recommendations given there reflect the
      current state of science and technology.

PMID- 19755454
TI  - Development of a highly controlled gas-phase nanoparticle generator for
      inhalation exposure studies.
AB  - We have developed a gas-phase nanoparticle generator that produces stable and
      well-defined size distributions for TiO(2). The online analyses of the gas-phase
      compounds and total number concentration of the generated particles as well as
      the off-line analysis of the filter samples confirmed the stability of the
      production. The major advantage of this reactor is that the test substance is
      directly in the aerosol phase, and thus no preprocessing is needed. This
      eliminates the physicochemical changes between bulk and administrated material
      during storing or processing. This system is easy to adjust to different
      experimental setups and precursors. As a result, well-characterized nanomaterials
      for inhalation exposure studies can be produced. At mass concentration of 30
      mg/Nm(3), the count mean diameter was 126 nm (geometric SD 1.6), mass mean
      diameter was 161 nm (2.0), mass median aerodynamic diameter was 125 nm, and the
      concentrations of harmful gas-phase by-products remained low. The produced powder
      consisted of crystals of anatase (77 vol%) and brookite (23 vol%), and its
      specific surface area was 69 m(2)/g.

PMID- 19755455
TI  - Liquid flame spray for generating metal and metal oxide nanoparticle test
      aerosol.
AB  - A flame-based method for generating nanoparticles with production rate in the
      order of g/min is presented to be used in a variety of applied studies concerning
      nanoparticle measurements and toxicological tests. In this study, ferric oxide,
      titanium dioxide, and silver nanoparticles were produced by this technique, as an
      example of the variety of producible compounds, and number and surface area were
      measured by state-of-art aerosol instruments. In the primary experiments of this
      study, the generator was used in a conventional way, in a fume cupboard, and the
      aerosol was measured from the exhaust duct of the cupboard. It has been shown
      that this steady, turbulent flame generator is also suitable for producing high
      concentration aerosols in a wider concept. The generated aerosol was measured by
      variety of aerosol instrumentation to show the applicability of the generator.
      When using the generator intentionally as a source of aerosol in the flame
      processing room, mean nanoparticle sizes of 5-60 nm and active surface area
      concentration ranges of 1-10,000 microm(2)/cm(3) were covered for the room
      aerosol.

PMID- 19755456
TI  - Occupational safety and health's role in sustainable, responsible nanotechnology:
      gaps and needs.
AB  - The newly fledged nanotechnologies offer opportunities for social development,
      but uncertainties prevail about their impact on human and environmental health.
      There is still a huge gap between technological progress and research into the
      health and safety aspects of nanomaterials. This is clear from the quantity of
      nanoproducts already on the market--more than 600--and the public and private
      funds dedicated to the development of nanotechnologies, which are almost a
      hundred times those available for research into their effects on health and
      safety. Estimates have it that by 2014, nanotechnologies will be widely used in
      our society and ten million new jobs will be created. Therefore, it becomes
      essential to plan an integrated approach to specific risk analysis at work. The
      following gaps and needs come to light: limited information, difficulties in
      relating nanotechnologies and production of nanomaterials to specific areas of
      application, efforts required to assess the hazards posed by nanomaterials in
      realistic exposure conditions, ethical issues about nanotechnology in the
      workplace likely to arise from today's knowledge about the hazards of
      nanomaterials and the risks they may pose to workers. An integrated approach to
      research, cooperation, and communication strategies is essential if we are to
      direct our efforts toward responsible and sustainable growth of nanotechnologies.

PMID- 19755457
TI  - Adverse effects associated with arginine alpha-ketoglutarate containing
      supplements.
AB  - The athletic performance supplement industry is a multibillion-dollar business
      and one popular category claims to increase nitric oxide (NO) production. We
      report three patients presenting to the emergency department with adverse
      effects. A 33-year-old man presented with palpitations, dizziness, vomiting, and
      syncope, after the use of NO(2) platinum. His examination and electrocardiogram
      (ECG) were normal. The dizziness persisted, requiring admission overnight. A 21
      year-old man with palpitations and near syncope had used a "nitric oxide"
      supplement. He was tachycardic to 115 bpm with otherwise normal examination.
      Laboratory values including methemoglobin, and ECG were unremarkable. He was
      treated with 1 L of saline with no change in heart rate. He was admitted for
      observation. A 24-year-old man presented after taking NO-Xplode with palpitations
      and a headache. His examination, laboratory values, and ECG were normal. He was
      discharged. The purported active ingredient in these products is arginine alpha
      ketoglutarate (AAKG), which is claimed to increase NO production by supplying the
      precursor L-arginine. The symptoms could be due to vasodilation from increased
      levels of NO, though other etiologies cannot be excluded. AAKG containing
      supplements may be associated with adverse effects requiring hospital admission.

PMID- 19755458
TI  - Two-year follow-up of two patients after severe thallium intoxication.
AB  - Information on the prognosis and electrophysiological follow-up of severe
      thallium poisoning is limited. We report two patients (mother and daughter) who
      were repeatedly exposed to thallium poisoning experienced hair loss,
      polyneuropathy, and visual impairment. Nerve conduction studies (NCSs), visual
      evoked potentials (VEP), brainstem auditory evoked potentials (BAEP) changes, and
      optical neuropathy developed within a few months latency after the first
      subjective signs. Normal findings of these electrophysiological methods in the
      first 2 weeks therefore led in one of our patients to exclusion of thallium as
      the cause of symptoms. Thallium poisoning was, however, later confirmed by
      toxicological analysis of blood and/or urine and feces in both the patients and
      in the microscopic hair analysis of the daughter. Both patients were treated with
      Prussian blue that increased the elimination of thallium in urine and feces. The
      hair loss was fully reversible. During a 2-year follow-up after the poisoning,
      polyneuropathy in the lower extremities improved substantially, but residual
      impairment in both motor and sensory function, NCSs, VEP, and BAEP remained.
      Additionally, severe asymmetrical vision impairment persists in both women, with
      central scotomata and impaired color discrimination in both eyes. Substantial
      improvement of their visual function is unlikely.

PMID- 19755459
TI  - Doping and effects of anabolic androgenic steroids on the heart: histological,
      ultrastructural, and echocardiographic assessment in strength athletes.
AB  - Anabolic androgenic steroids (AAS) are used by some athletes to enhance
      performance despite the health risk they may pose in some persons. This work was
      carried out to evaluate the possible structural and functional alterations in the
      heart using two-dimensional, M-mode, tissue Doppler imaging (TDI) and strain rate
      imaging (SRI) in athletes using supraphysiological doses of AAS. Additionally,
      the histological and ultrastructural changes in cardiac muscles of adult albino
      rats after injection of sustanon, as an example of AAS, were studied. Fifteen
      male bodybuilders using anabolic steroids constituted group 1, five male
      bodybuilders who are not using anabolic steroids constituted group 2, and five
      nonathletic males constituted negative control group (group 3). They were
      investigated by two-dimensional, M-mode, TDI and SRI. This study was performed on
      30 adult albino rats. They were divided into two groups. Group I (Control group)
      (10) was subdivided into negative control, subgroup 1a (5), and subgroup 1b (5),
      which received 0.8 ml olive oil intramuscular once a week for 8 weeks. Group II
      (Experimental group) (20) received sustanon 10 mg/kg intramuscularly once a week
      for 8 weeks. The heart specimens were prepared for light microscopy and
      transmission electron microscopy. Echocardiographic results showed that
      bodybuilders who use steroids have smaller left ventricular dimension with
      thicker walls, impaired diastolic function, as well as higher peak systolic
      strain rate in steroid-using bodybuilders as compared to the other two groups.
      Light microscopy examination of cardiac muscle fibers showed focal areas of
      degeneration with loss of striations and vacuolation in the experimental group.
      Ultrastructural examination showed disturbance of the banding pattern of the
      cardiac muscle fiber with disintegration, loss of striations, dehiscent
      intercalated disc, and interrupted Z-bands. Administration of supraphysiological
      doses of AAS caused severe deleterious effects in the myocardium both in athletes
      and in experimental animals. The SRI shows promise in the early detection of
      systolic dysfunction in those athletes who use steroids.

PMID- 19755460
TI  - Inconsistent approach to the treatment of chronic digoxin toxicity in the United
      States.
AB  - Evidence-based guidelines do not exist for the treatment of patients with chronic
      mild-moderate digoxin toxicity. We sought to evaluate differences among
      specialists in the use of digoxin-specific antibody fragments and the decision to
      admit these patients. A sample of cardiologists, emergency physicians, and
      medical toxicologists was surveyed. The survey detailed four hypothetical cases
      of chronic digoxin toxicity created by consensus among authors. All cases had the
      same digoxin concentration, but signs and symptoms varied in an attempt to
      explore four different thresholds. For each scenario, clinicians made decisions
      about admission and treatment. Survey response varied: cardiologists 17%,
      emergency physicians 6.7%, and toxicologists 39%. Statistically significant
      difference was found in the administration of Fab among cardiologists (67%),
      emergency physicians (82%), or toxicologists (91.5%) and admission rate
      (cardiologists 34%, emergency physicians 28%, and toxicologists 46%). Differences
      exist among clinicians of various specialties regarding treatment of chronic
      digoxin toxicity. These differences may reflect diverse perspectives or knowledge
      gaps and may translate into excess cost or less than ideal care. Exploring these
      differences may improve patient care, improve interactions among providers, and
      set the stage for development of consensus guidelines and research.

PMID- 19755461
TI  - Acute endosulfan poisoning: a retrospective study.
AB  - Endosulfan is a widely used insecticide that is associated with a high fatality
      rate in humans when ingested accidentally or with the aim of suicide. However,
      the literature concerning human endosulfan exposure is limited to case reports.
      Thus, we sought to 1) describe the clinical features of patients with acute
      endosulfan poisoning and 2) identify independent factors to predict patients'
      outcome. Fifty-two patients who presented with acute endosulfan poisoning between
      January 2001 and January 2007 were enrolled in this retrospective study. Sixteen
      (30.7%) of the 52 patients died, and 48 patients experienced seizures. Endosulfan
      poisoning caused the hypotension and the abnormalities on electrocardiogram at
      presentation. Over half of the patients developed complications, such as
      rhabdomyolysis, hepatic toxicity, and hypotension. These complications resolved
      without sequelae in the survival group. Refractory status epilepticus was the
      most common cause of death in this series (75.0%). Amount ingested being greater
      than 35 g of endosulfan was the most found to be an independent variable that
      predicted patient mortality. Patients with this risk factor must be treated
      aggressively during the early stage of endosulfan poisoning.

PMID- 19755462
TI  - Clinical evaluation of minimized extracorporeal circulation in high-risk coronary
      revascularization: impact on air handling, inflammation, hemodilution and
      myocardial function.
AB  - OBJECTIVE: We examined intraoperative microembolic signals (GME), inflammatory
      response, hemolysis, perioperative regional cerebral oxygen saturation (rSO(2)),
      myocardial protection and desorbed protein amount on oxygenator fibers in high
      risk patients undergoing coronary revascularization (CABG) with minimized and
      conventional cardiopulmonary bypass (CPB). METHODS: Over a ten-month period, 40
      Euroscore 6+ patients undergoing CABG were prospectively randomized to one of the
      two perfusion protocols (N=20): Group 1: minimized extracorporeal circuits (Mini
      CPB) (ROCsafe MPC, Terumo, Ann Arbor, MI, USA) and Group 2: conventional
      extracorporeal circuits (CECC) (Capiox SX18, Terumo, USA). Serum creatinine
      kinase-MB (CKMB), free hemoglobin, interleukin-6 (IL-6) and C3a levels were
      measured. Blood samples were collected at T1: following induction of anesthesia;
      T2: thromboelastography control; T3:15 min after commencement of CPB; T4: before
      cessation of CPB; T5: 15 min after protamine reversal and T6: ICU. RESULTS: Serum
      IL-6 levels were significantly lower in the Mini-CPB group at T4 and T5 and C3a
      levels were significantly less in the Mini-CPB group at T3, T4 and T5 vs. CECC
      (p<0.01). CKMB levels in coronary sinus blood demonstrated well preserved
      myocardium in the Mini-CPB group. Percentage expression of neutrophil CD11b/CD18
      levels were significantly lower in the Mini-CPB group at T4 and T5 (p<0.05).
      There were no significant differences in air handling characteristics or free
      plasma hemoglobin levels in either circuit. rSO(2) measurements were
      significantly better at T3 and T4 in the Mini-CPB vs. CECC (p<0.05) and always
      higher in the Mini-CPB during follow-up. Blood protein adsorption analysis of
      oxygenator membranes demonstrated a significantly increased amount of
      microalbumin on CECC fibers (p<0.05). CONCLUSION: Mini-CPB provided a comfort and
      safety level similar to conventional control via satisfactory air handling,
      attenuated inflammatory response and hemodilution, with a better clinical outcome
      in patients undergoing high-risk CABG.

PMID- 19755463
TI  - The use of a mini bypass circuit for minimally invasive mitral valve surgery.
AB  - INTRODUCTION: The purpose of the study is to clinically evaluate minimally
      invasive mitral valve surgeries (MIMVS) using a mini bypass circuit. The
      challenge to perfusion is to keep pace with MIMVS, with demonstrated improvements
      in perfusion-related technologies. METHODS: From October 28, 2005 to September
      10, 2008, we retrospectively evaluated thirty-four elective cases which used the
      mini-circuit (Medtronic Resting Heart System), with respect to safety, efficacy,
      cannulation technique, blood usage, resultant hemoglobin, length of ICU and
      hospital stay, and complications. CONCLUSION: The Medtronic Resting Heart System
      alleviates many factors, such as high shear stress, turbulence, air to blood
      interface and decreased oncotic pressure caused by hemodilution, providing more
      efficient perfusion to our MIMVS patients. We demonstrate, with minor circuit
      modifications and attention to venous air issues, that this mini-circuit can be
      used safely and effectively, while being associated with improvements in patient
      outcomes.

PMID- 19755464
TI  - Does remote ischemic preconditioning prevent delayed hippocampal neuronal death
      following transient global cerebral ischemia in rats?
AB  - OBJECTIVE: To determine if remote ischemic preconditioning (RIPC) induced by
      transient limb ischemia is protective against delayed hippocampal neuronal death
      in rats undergoing transient global cerebral ischemia (GCI). METHOD: Animals were
      randomized into 3 groups: Group I (Control, n = 5) underwent sham procedure,
      namely, general anesthesia x 2, without cerebral ischemia; Group II (RIPC + GCI,
      n = 5) was subjected to RIPC, induced by transient left hind limb ischemia under
      general anesthesia prior to GCI; Group III (GCI only, n = 5) underwent sham
      procedure under general anesthesia prior to GCI. Twenty-four hours after the RIPC
      or sham procedure, a transient GCI was induced for 8 minutes in Groups II and III
      by means of bilateral common carotid artery occlusion and hypotension.
      Hippocampal CA1 neurons were histologically examined at 7 days after ischemia.
      RESULTS: There was no significant difference between the RIPC group and the
      ischemia only group. The number of neurons in the RIPC group were 0.90 (95% CI
      0.20, 4.08) times the number in the ischemia group (p=0.89). The number of
      neurons in the RIPC group were 0.03 (95% CI 0.01, 0.10) times the number in the
      Control group (p=0.0001). CONCLUSION: Second window of the RIPC does not prevent
      hippocampal CA1 neuronal death at 7 days after transient global cerebral
      ischemia.

PMID- 19755465
TI  - Bloodless aortic valve and ascending aorta replacement surgery requiring
      circulatory arrest: two case studies.
AB  - Blood and/or blood product transfusions are common during and after complicated
      cardiac procedures. Replacement of the aortic valve, ascending aorta, and
      coronary implantation requiring circulatory arrest are high-risk procedures.
      Blood product transfusions only add to the morbidity and mortality rates
      associated with these types of procedures. Perfusion strategies must be
      incorporated to decrease the effects of hemodiluton due to cardiopulmonary bypass
      (CPB), and preserve platelets and clotting factors needed for hemostasis, post
      operatively. We are reporting two consecutive cases where the patients presented
      with aortic valve stenosis accompanying an ascending aortic aneurysm requiring
      surgical correction using circulatory arrest. Neither patient required any blood
      or blood product donation throughout their hospital stay. Our strategies included
      minimizing our bypass circuit, utilization vacuum-assisted venous drainage,
      plasma sequestration, total circuit retrograde autologous priming (RAP), and cell
      salvage.

PMID- 19755466
TI  - Preoperative screening and management of carotid artery disease in patients
      undergoing cardiac surgery.
AB  - BACKGROUND: Carotid artery stenosis (CAS) is a well-known risk factor for
      perioperative stroke in cardiac surgery. It is unclear whether preoperative
      carotid screening should be applied to all patients. Carotid intervention
      concomitantly with cardiac operations is also controversial. Our objective was to
      identify the prevalence of significant CAS and its related risk factors by
      applying a protocol of preoperative carotid screening to all patients undergoing
      cardiac surgery. METHODS: We studied 307 patients who were primarily screened
      preoperatively by duplex Doppler ultrasonography. Catheter carotid angiography or
      transcranial Doppler was performed on equivocal cases. Univariate and
      multivariate analyses were applied across selected parameters to identify risk
      factors for significant CAS (> 70%). The prevalence of CAS and perioperative
      stroke rates were determined. RESULTS: Twenty-two patients with severe and 18
      with moderate carotid stenosis were identified. Further radiological evaluation
      with catheter carotid angiography and transcranial Doppler confirmed the presence
      of significant CAS in 20 patients who underwent carotid stenting or
      endarterectomy before the open heart surgery. The cardiac surgeon was free to
      modify the surgical technique according to the preoperative assessment. No
      patient had major stroke perioperatively, while two minor strokes with complete
      neurologic recovery have been documented. The history of stroke and the presence
      of bruit on clinical examination were the only significant predictors of severe
      carotid disease. CONCLUSION: Careful clinical examination together with detailed
      previous history taking can identify the majority of patients with CAS. Further
      data are required for the construction of a scientifically valid policy as a
      guideline.

PMID- 19755467
TI  - Case control study of gastrointestinal complications after cardiopulmonary bypass
      heart surgery.
AB  - BACKGROUND: Gastrointestinal complications (GIC) after cardiopulmonary bypass
      (CPB) surgery are rare, but, nevertheless, extremely dangerous.The identification
      of risks for GIC may be helpful in planning appropriate perioperative management
      strategies. The aim of the present study was to analyze perioperative factors of
      GIC in patients undergoing CPB surgery. METHODS: We retrospectively analysed 206
      patients who underwent GIC after cardiopulmonary bypass surgery from 2000 to 2007
      and compared them with 206 matched control patients (matched for surgery,
      temperature, hemodilution and date). Univariate analysis and multiple logistic
      regression analysis were performed on 12 risk factors. RESULT: Sex and types of
      cardioplegia perfusate did not significantly influence the GIC after CPB surgery.
      Multiple logistic regression revealed that CPB time, preoperative serum
      creatinine (PSC) > or = 179 mg/dL, emergency surgery, perfusion pressure < or =40
      mmHg, low cardiac output syndrome (LCOS), age > or = 61, mechanical ventilation >
      or =96 h, New York Heart Association (NYHA) class III and IV were predictors of
      the occurrence of GIC after CPB surgery. Perfusion pressure and aprotinin
      administration were protective factors. CONCLUSION: Gastrointestinal
      complications after CPB surgery could be predictive in the presence of the above
      risk factors. This study suggests that GIC can be reduced by maintenance of
      higher perfusion pressure and shortening the time on CPB and ventilation.

PMID- 19755468
TI  - Late gadolinium enhancement-cardiovascular magnetic resonance identifies coronary
      artery disease as the aetiology of left ventricular dysfunction in acute new
      onset congestive heart failure.
AB  - AIMS: We evaluated the ability of late gadolinium enhancement (LGE) using
      cardiovascular magnetic resonance (CMR) to identify acute new-onset heart failure
      (HF) with left ventricular systolic dysfunction (LVSD), whether or not in
      relation to underlying coronary artery disease (CAD), in patients with no
      clinical evidence of associated ischaemic cardiomyopathy. METHODS AND RESULTS:
      Hundred consecutive patients admitted with acute new-onset decompensated HF and
      EF <40%, with no clinical or electrocardiographic data suggestive of CAD. The
      patients were classified according to the presence or absence of significant CAD
      (stenosis > or =70% in at least one major vessel). Twenty-one patients (21%) had
      significant CAD. Seventy-nine (79%) had no lesions. Eighteen of the 21 patients
      (85%) with CAD had subendocardial/transmural LGE. In the diagnosis of CAD, LGE
      has a sensitivity of 85.7% (95% CI, 80-91) and specificity of 92.4% (95% CI, 87
      96), respectively, with a negative predictive value of 96% (95% CI, 90-99). It
      has an area under the receiver operating characteristic curve of 0.906 (95% CI,
      0.814-0.998). CONCLUSION: In patients with new-onset HF and LVSD for whom there
      are no clinical and exploratory data suggestive of ischaemic heart disease, CMR
      with LGE is an excellent means of ruling out significant CAD and is a valid
      alternative to angiography.

PMID- 19755469
TI  - Feasibility, safety, and efficacy of real-time three-dimensional transoesophageal
      echocardiography for guiding device closure of interatrial communications:
      initial clinical experience and impact on radiation exposure.
AB  - AIMS: Our aim was to assess the feasibility and safety of real-time (RT) three
      dimensional (3D) transoesophageal echocardiography (TEE) for guiding
      transcatheter closure of interatrial communications and to evaluate its
      additional benefit over conventional 2D TEE in reducing radiation exposure for
      the patient. METHODS AND RESULTS: Twenty-five patients undergoing device closure
      of their interatrial defect had the procedure guided by fluoroscopy, 2D TEE, and
      RT 3D TEE. We retrospectively compared this group with a historical control group
      in which interventional guidance was performed using fluoroscopy and 2D TEE
      alone. The application of RT 3D TEE allowed safe device deployment in all
      patients without any complications, resulting in a reduction of mean fluoroscopy
      time (10 +/- 6 to 6 +/- 4 min, P < 0.01), mean dose area product (DAP) (964 +/-
      628 to 535 +/- 464 cGy cm(2), P < 0.01), and mean DAP per individual body surface
      area (494 +/- 317 to 273 +/- 221 cGy cm(2)/m(2), P < 0.01). CONCLUSION: RT 3D TEE
      as an adjunct to 2D TEE is a feasible and safe tool to guide transcatheter device
      closure of interatrial communications, resulting in a reduction of radiation
      exposure. These data indicate that RT 3D TEE can be used to safely monitor
      interatrial defect closure in clinical routine.

PMID- 19755470
TI  - MicroRNAs resolve an apparent conflict between annelid systematics and their
      fossil record.
AB  - Both the monophyly and inter-relationships of the major annelid groups have
      remained uncertain, despite intensive research on both morphology and molecular
      sequences. Morphological cladistic analyses indicate that Annelida is
      monophyletic and consists of two monophyletic groups, the clitellates and
      polychaetes, whereas molecular phylogenetic analyses suggest that polychaetes are
      paraphyletic and that sipunculans are crown-group annelids. Both the monophyly of
      polychaetes and the placement of sipunculans within annelids are in conflict with
      the annelid fossil record--the former because Cambrian stem taxa are similar to
      modern polychaetes in possessing biramous parapodia, suggesting that clitellates
      are derived from polychaetes; the latter because although fossil sipunculans are
      known from the Early Cambrian, crown-group annelids do not appear until the
      latest Cambrian. Here we apply a different data source, the presence versus
      absence of specific microRNAs--genes that encode approximately 22 nucleotide non
      coding regulatory RNAs--to the problem of annelid phylogenetics. We show that
      annelids are monophyletic with respect to sipunculans, and polychaetes are
      paraphyletic with respect to the clitellate Lumbricus, conclusions that are
      consistent with the fossil record. Further, sipunculans resolve as the sister
      group of the annelids, rooting the annelid tree, and revealing the polarity of
      the morphological change within this diverse lineage of animals.

PMID- 19755471
TI  - Expression of sialidase and dystroglycan in human glomerular diseases.
AB  - BACKGROUND: alpha-Dystroglycan (alpha-DG) is a negatively charged glycoprotein
      that covers the surface of podocytes. A decreased glomerular expression of alpha
      DG has been described in minimal change nephropathy (MCN), but not in focal
      segmental glomerulosclerosis (FSGS). This was suggested as a tool to distinguish
      these diseases. Sialic acid is a negatively charged carbohydrate extensively
      present on both alpha-DG and podocalyxin, which is also expressed on podocytes.
      Intrarenal perfusion with bacterial sialidase leads to foot process effacement
      and proteinuria. This is the first study on the expression of endogenous
      glomerular sialidase; furthermore, the expression of dystroglycan was re
      evaluated. METHODS: The expression of alpha-DG and sialidase was investigated by
      immunofluorescence in kidney biopsies of patients with MCN (n = 5), FSGS (n =
      15), proliferative lupus nephritis (LN, n = 9), membranous glomerulopathy (MG, n
      = 10) and normal human kidneys (NHK, n = 4). The urinary sialic acid
      concentration was measured using a newly developed LC-tandem mass spectrometry
      method. RESULTS: A 3-fold increased glomerular expression of sialidase was found
      in MG, accompanied with an increased urinary sialic acid concentration in two MG
      patients. However, we did not observe major changes in the expression of alpha-DG
      in patients with the above-mentioned glomerular diseases compared to NHK, also
      not between MCN and FSGS. CONCLUSIONS: Endogenous glomerular sialidase expression
      is increased in MG, which might represent a novel mechanism for the loss of
      negative charge in the glomerular capillary filter. The expression of
      dystroglycan cannot be used as a diagnostic tool to differentiate between
      glomerular diseases.

PMID- 19755472
TI  - Kidney calling lung and call back: how organs talk to each other.

PMID- 19755473
TI  - Severe paediatric systemic lupus erythematosus nephritis--a single-centre
      experience.
AB  - BACKGROUND: Paediatric patients with systemic lupus erythematosus (SLE) often
      have severe presentations including lupus nephritis (LN). Few paediatric studies
      have evaluated the anticardiolipin antibody (aCL) and renal histology. The
      purpose of this study was to evaluate clinicopathologic features, including aCL,
      short-term clinical and renal histologic outcomes of paediatric patients with new
      onset SLE nephritis. METHODS: We conducted a single centre, retrospective
      inception cohort study. Charts were reviewed at presentation (initial renal
      biopsy), 6-month (follow-up biopsy) and 12-month follow-up. RESULTS: The
      population consisted of 21 patients (median age, 14.5 years): 19/21 were female,
      6/21 African American, 3/21 Asian, 9/21 Caucasian and 3/21 Hispanic. At
      presentation, 19/21 had elevated aCL, 15/21 hypertensive, 12/21 nephrotic and
      7/21 required haemodialysis (HD)-2/7 HD patients had thrombotic microangiopathy,
      1/7 crescentic glomerulonephritis. Two patients had thromboembolism: both had
      aCL, were taking oral contraceptives and required HD, one was nephrotic and the
      other had elevated lupus anticoagulant. Initial biopsies revealed 6/21 ISN/RPS
      class II nephritis, 3/21 class III, 7/21 class IV and 5/21 class V. Treatment
      consisted of methylprednisolone, corticosteroids, cyclophosphamide or
      mycophenolate mofetil. Follow-up biopsies revealed 12/13 to have improved
      histology. Indication for a follow-up biopsy was severe illness at presentation.
      At 12-month follow-up, no patients were nephrotic (P < 0.001) or required HD (P <
      0.001), and 3/14 had elevated aCL (P < 0.001). CONCLUSION: Elevated aCL,
      hypertension, nephrotic syndrome and need for HD were common presentations among
      our paediatric SLE nephritis population. Renal histology and aCL were helpful in
      the therapeutic management.

PMID- 19755474
TI  - Survival and transplantation in end-stage renal disease: a prospective study of a
      multiethnic population.
AB  - INTRODUCTION: Accurate assessment of determinants of patient survival in end
      stage renal disease is important for counselling, clinical management and
      resource planning. To address this we have analysed survival and risk factors for
      survival for patients treated for end-stage renal disease in a multi-ethnic UK
      population. METHODS: A multicentre prospective observational cohort study was
      performed in four teaching hospital renal units serving a total population of
      four million people. A total of 884 consecutive patients treated with renal
      replacement therapy were studied. Cox proportional hazard modelling and adjusted
      survival curves were used to assess the impact of a range of variables on
      patients surviving dialysis for more than 90 days. Further analysis was
      undertaken to determine the likelihood of transplantation in different ethnic
      groups. RESULTS: Survival was 29% after a mean and median follow up of 4.6 and
      4.2 years, respectively. Factors associated with worse survival included the
      following: age; for each decade of life the relative risk (RR) of death was 1.52
      (95% confidence intervals 1.41-1.65, p < 0.0001); comorbidity, one or two
      comorbid conditions, RR = 1.56 (95% CI 1.24-1.95, p < 0.001) and three or more
      comorbid conditions, RR = 2.34 (1.68-3.27, p < 0.001). Factors associated with
      better survival included the following: south-Asian ethnicity, RR = 0.6 (0.46
      0.80, p < 0.001); renal transplantation, RR = 0.20 (95% CI 0.11-0.59, p < 0.0001)
      and glomerulonephritis as the primary renal disease, RR = 0.70 (0.50-0.97, p =
      0.04). Factors associated with likelihood of transplantion were having a
      functioning fistula/peritoneal dialysis catheter at start of dialysis (RR 1.91,
      95% CI 1.24-2.94, p = 0.003) and glomerulonephritis (RR 9.54, 95% CI 2.43-37.64,
      p = 0.001). Patients were less likely to receive if they were black (RR 0.10, 95%
      CI 0.02-0.34, p < 0.001), South Asian (RR 0.64, 95% CI 0.42-0.97, p = 0.037),
      diabetic (RR 0.06, 95% CI 0.01-0.23, p < 0.001) and had one or two comorbid
      conditions (RR 0.51, 95% CI 0.32-0.82, p = 0.06). Every decade increase in age
      was also associated with a lesser likelihood of transplantation (RR 0.55, 95% CI
      0.49-0.61, p < 0.001). Discussion. Risk stratification at commencement of chronic
      dialysis may predict long-term survival in different patient groups. As expected
      ethnic minorities are less likely to receive a transplant and this should be
      addressed by the new waiting list prioritization. The better survival on dialysis
      in this population of patients with south-Asian ethnicity is unexplained and this
      requires further investigation.

PMID- 19755475
TI  - Influence of arterial elasticity and vessel dilatation on arteriovenous fistula
      maturation: a prospective cohort study.
AB  - BACKGROUND: Arteriovenous fistula maturation requires dilatation of the
      anastomosed artery and vein. The factors that affect dilatation and the
      mechanisms by which dilatation promotes maturation are not understood. This pilot
      study tested two hypotheses: that low arterial elasticity is associated with
      maturation failure, and that vessel dilatation is required for adequate fistula
      blood flow during dialysis. METHODS: Thirty-two patients underwent preoperative
      measurement of small artery elasticity index, and pre-anastomosis measurement of
      artery and vein luminal diameters during fistula surgery. Fistulas were
      considered mature if they were used successfully in three consecutive treatments
      within 6 months. A mathematical model was used to determine whether vessel
      dilatation is needed for adequate fistula flow. RESULTS: Six fistulas were
      excluded from analysis of maturation because dialysis did not begin within 6
      months. Twenty-one of the remaining 26 fistulas were located in the upper arm.
      Six of 26 failed to mature, and all 6 developed stenosis. The average small
      artery elasticity index was lower in failed than in matured fistulas (2.25 versus
      3.71 ml/ mmHg x 100, P = 0.02). Artery and vein diameters of the 32 patients
      ranged from 2.5 to 5.0 and 3.5 to 7.0 mm, respectively. When the diameters were
      applied to the mathematical model, predicted fistula flows ranged from 412 to
      1380 ml/min. CONCLUSIONS: Low arterial elasticity is associated with stenosis and
      fistula maturation failure. However, vessel dilatation is not needed for adequate
      blood flow except at the smaller diameters in this study. We speculate that low
      elasticity promotes development of stenosis. Larger studies are needed to confirm
      these promising results and to determine whether therapies directed at improving
      elasticity can improve maturation.

PMID- 19755476
TI  - Protein-bound uraemic toxin removal in haemodialysis and post-dilution
      haemodiafiltration.
AB  - BACKGROUND: The accumulation of larger and protein-bound toxins is involved in
      the uraemic syndrome but their elimination by dialysis therapy remains difficult.
      In the present study, the impact of the albumin permeability of recently
      introduced advanced high-flux dialysis membranes on the removal of such
      substances was tested in haemodialysis and online post-dilution
      haemodiafiltration. METHODS: Two types of polyethersulfone membranes only
      differing in albumin permeability (referred as PU- and PU+) were compared in
      eight patients on maintenance dialysis in a prospective cross-over manner.
      Treatment settings were identical for individual patients: time 229 +/- 22 min;
      blood flow rate 378 +/- 33 mL/min; dialysate flow rate 500 mL/min; substitution
      flow rate in haemodiafiltration 94 +/- 9 mL/min. Removal of the protein-bound
      compounds p-cresyl sulfate (pCS) and indoxyl sulfate (IS) was determined by
      reduction ratios (RRs), dialytic clearances and mass in continuously collected
      dialysate. In addition, the elimination of the low-molecular weight (LMW)
      proteins beta(2)-microglobulin, cystatin c, myoglobin (myo), free retinol-binding
      protein (rbp) and albumin was measured. RESULTS: Plasma levels of the protein
      bound toxins were significantly decreased by all treatment forms. However, the
      decreases were comparable between dialysis membranes and between haemodialysis
      and haemodiafiltration. The RRs of total pCS ranged between 40.4 +/- 25.3 and
      47.8 +/- 10.3% and of total IS between 50.4 +/- 2.6 and 54.6 +/- 8.7%.
      Elimination of free protein-bound toxins as assessed by their mass in dialysate
      closely correlated positively with the pre-treatment plasma concentrations being
      r = 0.920 (P < 0.001) for total pCS and r = 0.906 (P < 0.001) for total IS,
      respectively. Compared to haemodialysis, much higher removal of all LMW proteins
      was found in haemodiafiltration. Dialysis membrane differences were only obvious
      in haemodialysis for the larger LMW proteins myo and rbp yielding significantly
      higher RRs for PU+ (myo 46 +/- 9 versus 37 +/- 9%; rbp 18 +/- 5 versus 15 +/- 5%;
      P < 0.05). Additionally, the albumin loss varied between membranes and treatment
      modes being undetectable with PU- in haemodialysis and highest with PU+ in
      haemodiafiltration (1430 +/- 566 mg). CONCLUSIONS: The elimination of protein
      bound compounds into dialysate is predicted by the level of pre-treatment plasma
      concentrations and depends particularly on diffusion. Lacking enhanced removal in
      online post-dilution haemodiafiltration emphasizes the minor significance of
      convection for the clearance of these solutes. Compared to LMW proteins, the
      highly protein-bound toxins pCS and IS are less effectively eliminated with all
      treatment forms. For a sustained decrease of pCS and IS plasma levels,
      alternative strategies promise to be more efficient therapy forms.

PMID- 19755477
TI  - Basal, pulsatile, entropic (patterned), and spiky (staccato-like) properties of
      ACTH secretion: impact of age, gender, and body mass index.
AB  - BACKGROUND: Age, gender, and BMI determine ultradian modes of LH and GH
      secretion, viz., pulsatile, basal, pattern-defined regularity [approximate
      entropy (ApEn)] and spikiness (sharp, brief excursions). Whether the same
      determinants apply to ACTH secretion is not known. SETTING: The study was
      conducted at a tertiary medical center. SUBJECTS: We studied normal women (n =
      22) and men (n = 26) [ages, 23-77 yr; body mass index (BMI), 21-32 kg/m(2)].
      METHODS: Volunteers underwent 10-min blood sampling to create 24-h ACTH
      concentration profiles. OUTCOMES: Dynamic measures of ACTH secretion were
      studied. RESULTS: Mean ACTH concentrations (R(2) = 0.15; P = 0.006) and both
      pulsatile (R(2) = 0.12; P = 0.018) and basal (nonpulsatile) (R(2) = 0.16; P =
      0.005) ACTH secretion correlated directly with BMI (n = 48). Men had greater
      basal (P = 0.047), pulsatile (P = 0.031), and total (P = 0.010) 24-h ACTH
      secretion than women, including when total secretion was normalized for BMI (P =
      0.019). In men, both ACTH-cortisol feedforward and cortisol-ACTH feedback
      asynchrony (cross-ApEn) increased with age (R(2) = 0.20 and 0.22; P = 0.021 and
      0.018). ACTH spikiness rose with age (P = 0.046), principally in women.
      Irregularity of cortisol secretion (ApEn) increased with age (n = 48; P = 0.010),
      especially in men. In both sexes, percentage pulsatile ACTH secretion predicted
      24-h mean cortisol concentrations (R(2) = 0.14; P = 0.009). CONCLUSION: Valid
      comparisons of ultradian ACTH dynamics will require cohorts matched for age,
      gender, and BMI, conditions hitherto not satisfied in most physiological studies
      of this axis.

PMID- 19755478
TI  - Carotid vascular abnormalities in primary hyperparathyroidism.
AB  - CONTEXT: Data on the presence, extent, and reversibility of cardiovascular
      disease in primary hyperparathyroidism (PHPT) are conflicting. OBJECTIVE: This
      study evaluated carotid structure and function in PHPT patients compared with
      population-based controls. DESIGN: This is a case-control study. SETTING: The
      study was conducted in a university hospital metabolic bone disease unit.
      PARTICIPANTS: Forty-nine men and women with PHPT and 991 controls without PHPT
      were studied. OUTCOME MEASURES: We measured carotid intima-media thickness (IMT),
      carotid plaque presence and thickness, and carotid stiffness, strain, and
      distensibility. RESULTS: IMT, carotid plaque thickness, carotid stiffness, and
      distensibility were abnormal in PHPT patients, and IMT was higher in patients
      than controls (0.959 vs. 0.907 mm, P < 0.0001). In PHPT, PTH levels, but not
      calcium concentration, predicted carotid stiffness (P = 0.04), strain (P = 0.06),
      and distensibility (P = 0.07). Patients with increased carotid stiffness had
      significantly higher PTH levels than did those with normal stiffness (141 +/- 48
      vs. 94.9 +/- 44 pg/ml, P = 0.002), and odds of abnormal stiffness increased 1.91
      (confidence interval = 1.09-3.35; P = 0.024) for every 10 pg/ml increase in PTH,
      adjusted for age, creatinine, and albumin-corrected calcium. CONCLUSIONS: Mild
      PHPT is associated with subclinical carotid vascular manifestations. IMT, a
      predictor of cardiovascular outcomes, is increased. Measures of carotid stiffness
      are associated with extent of PTH elevation, suggesting that those with more
      severe PHPT may have impaired vascular compliance and that PTH, rather than
      calcium, is the mediator.

PMID- 19755479
TI  - Subcutaneous rather than visceral adipose tissue is associated with adiponectin
      levels and insulin resistance in young men.
AB  - INTRODUCTION: Studies on the association between adiponectin, body composition,
      and insulin resistance (IR) have been conflicting. AIM: Our aim was to evaluate
      the impact of body composition on adiponectin and IR determined by homeostasis
      model assessment (HOMA) in a population-based study on relatively healthy young
      men, minimizing the possible effects of age, obesity, and severe comorbidity.
      DESIGN, METHODS, AND SUBJECTS: A population-based, cross-sectional study of 783
      men aged 20-29 yr, randomly drawn from the Danish Central Personal Registry.
      Adiponectin was assessed using an in-house assay, and IR was determined using
      HOMA. Central fat mass (CFM) and lower extremity fat mass (LEFM) was measured by
      dual-energy x-ray absorptiometry, and visceral adipose tissue (VAT), sc adipose
      tissue (SAT), and thigh fat area (TFA) were assessed by magnetic resonance
      imaging. RESULTS: Using multiple linear regression analysis, adiponectin
      correlated negatively with CFM (r = -0.27; P < 0.001) and SAT (r = -0.20; P <
      0.001) and positively with LEFM (r = 0.19; P < 0.001) and TFA (r = 0.18; P <
      0.001), whereas VAT did not associate significantly. In multiple linear
      regression analysis, HOMA-IR (dependent variable), correlated significantly with
      CFM (r = 0.27; P < 0.001) and SAT (r = 0.15; P < 0.001), whereas LEFM, VAT, or
      TFA did not correlate. Adiponectin was an independent predictor of HOMA-IR in
      both analyses (r = -0.14; P < 0.001). CONCLUSION: SAT rather than VAT was
      inversely associated with adiponectin levels, and, interestingly, fat on the
      lower extremities was positively associated with adiponectin. Focusing on insulin
      resistance, SAT rather than VAT and TFA independently predicted a higher HOMA-IR.
      The observation that adiponectin was independently associated with lower HOMA-IR
      must be repeated in other populations.

PMID- 19755480
TI  - Hypogonadotropic hypogonadism due to a novel missense mutation in the first
      extracellular loop of the neurokinin B receptor.
AB  - CONTEXT: The neurokinin B (NKB) receptor, encoded by TACR3, is widely expressed
      within the central nervous system, including hypothalamic nuclei involved in
      regulating GnRH release. We have recently reported two mutations in transmembrane
      segments of the receptor and a missense mutation in NKB in patients with
      normosmic isolated hypogonadotropic hypogonadism (nIHH). PATIENTS AND METHODS: We
      sequenced the TACR3 gene in a family in which three siblings had nIHH. The novel
      mutant receptor thus identified was studied in a heterologous expression system
      using calcium flux as the functional readout. RESULTS: All affected siblings were
      homozygous for the His148Leu mutation, in the first extracellular loop of the NKB
      receptor. The His148Leu mutant receptor exhibited profoundly impaired signaling
      in response to NKB (EC(50) = 3 +/- 0.1 nm and >5 microm for wild-type and
      His148Leu, respectively). The location of the mutation in an extracellular part
      of the receptor led us also to test whether senktide, a synthetic NKB analog, may
      retain ability to stimulate the mutant receptor. However, the signaling activity
      of the His148Leu receptor in response to senktide was also severely impaired
      (EC(50) = 1 +/- 1 nm for wild-type and no significant response of His148Leu to 10
      microm). CONCLUSIONS: Homozygosity for the TACR3 His148Leu mutation leads to
      failure of sexual maturation in humans, whereas signaling by the mutant receptor
      in vitro in response to either NKB or senktide is severely impaired. These
      observations further strengthen the link between NKB, the NKB receptor, and
      regulation of human reproductive function.

PMID- 19755481
TI  - Is the metalloendopeptidase EC 3.4.24.15 (EP24.15), the enzyme that cleaves
      luteinizing hormone-releasing hormone (LHRH), an activating enzyme?
AB  - LHRH (GNRH) was first isolated in the mammalian hypothalamus and shown to be the
      primary regulator of the reproductive neuroendocrine axis comprising of the
      hypothalamus, pituitary and gonads. LHRH acts centrally through its initiation of
      pituitary gonadotrophin release. Since its discovery, this form of LHRH (LHRH-I)
      has been shown to be one of over 20 structural variants with a variety of roles
      in both the brain and peripheral tissues. LHRH-I is processed by a zinc
      metalloendopeptidase EC 3.4.24.15 (EP24.15) that cleaves the hormone at the fifth
      and sixth bond of the decapeptide (Tyr(5)-Gly(6)) to form LHRH-(1-5). We have
      previously reported that the auto-regulation of LHRH-I (GNRH1) gene expression
      and secretion can also be mediated by itself and its processed peptide, LHRH-(1
      5), centrally and in peripheral tissues. In this review, we present the evidence
      that EP24.15 is the main enzyme of LHRH metabolism. Following this, we look at
      the metabolism of other neuropeptides where an active peptide fragments is formed
      during degradation and use this as a platform to postulate that EP24.15 may also
      produce an active peptide fragment in the process of breaking down LHRH. We close
      this review by the role EP24.15 may have in regulation of the complex LHRH
      system.

PMID- 19755482
TI  - Regulation of endometrial vascular remodelling: role of the vascular endothelial
      growth factor family and the angiopoietin-TIE signalling system.
AB  - Angiogenesis, lymphangiogenesis and vascular maturation occur on a regular,
      physiological basis in human endometrium. These processes form part of a
      continuum of vascular remodelling involving numerous regulatory factors. Key
      factors include vascular endothelial growth factor (VEGF)A, VEGFC and VEGFD, and
      their associated receptors VEGFR1, VEGFR2 and VEGFR3. A second group of vascular
      regulatory proteins belongs to the angiopoietin (ANG)-TIE system. Although
      members of the VEGF family and the ANG-TIE system are represented in the
      endometrium, our understanding of how these different molecules interact to
      regulate remodelling of the blood and lymphatic vasculature present in the
      endometrium is still limited. A review of the current information is provided.

PMID- 19755483
TI  - Prolactin regulation of testosterone secretion and testes growth in DLS rams at
      the onset of seasonal testicular recrudescence.
AB  - Our objective was to test the hypothesis that prolactin (PRL) acts at both the
      pituitary and testis levels to regulate testosterone secretion in the adult ram.
      The focus was on the mid-regression to mid-redevelopment stages of a photoperiod
      condensed 'seasonal' testicular cycle. DLS rams (six per group) were given daily
      s.c. injections of bromocriptine (4 mg) or vehicle during the entire period.
      Serum PRL concentration in control rams peaked at 103.4+/-22.1 ng/ml in late
      regression and then steadily declined (P<0.01) to 19.5+/-4.3 ng/ml, whereas PRL
      in treated rams was always < or =4.0 ng/ml. Suppression of PRL tended (P<0.10) to
      increase the amplitude of natural LH pulses (transition stages) or reduce the
      number of LH receptors in the testis (regressed stage), although neither change
      disturbed testosterone levels in peripheral blood. These subtle changes were
      accompanied by significant (P<0.05) alterations in the capability of the
      pituitary to release LH (85% more) and of the testes to secrete testosterone (20%
      less). These effects of PRL were unmasked when rams were given highly stimulative
      i.v. injections of GNRH (single 3 microg dose) and NIH-oLH-S24 (three 5 microg
      doses given 20 min apart) respectively. PRL insufficiency also appeared to slow
      down the 'seasonal' rise in FSH secretion and slightly delayed (2 weeks) the
      times when the testes began to grow and were first significantly (P<0.05)
      enlarged from the regressed state. We conclude that PRL is an important part of
      the intricate regulation of the pituitary-gonadal system in moderately seasonal
      DLS rams.

PMID- 19755484
TI  - Molecular mechanisms of gene regulation during Drosophila spermatogenesis.
AB  - The differentiation of sperm from morphologically unremarkable cells into highly
      specialised free-living, motile cells requires the co-ordinated action of a very
      large number of gene products. The expression of these products must be regulated
      in a developmental context to ensure normal cellular differentiation. Many genes
      essential for spermatogenesis are not used elsewhere in the animal, or are
      expressed elsewhere, but using a different transcription regulation module.
      Spermatogenesis is thus a good system for elucidating the principles of tissue
      specific gene expression, as well as being interesting in its own right. Here, I
      discuss the regulation of gene expression during spermatogenesis in Drosophila,
      focussing on the processes underlying the expression of testis-specific genes in
      the male germline.

PMID- 19755485
TI  - Hypoxia inducible factors regulate pluripotency and proliferation in human
      embryonic stem cells cultured at reduced oxygen tensions.
AB  - Human embryonic stem (hES) cells are routinely cultured under atmospheric, 20%
      oxygen tensions but are derived from embryos which reside in a 3-5% oxygen
      (hypoxic) environment. Maintenance of oxygen homeostasis is critical to ensure
      sufficient levels for oxygen-dependent processes. This study investigates the
      importance of specific hypoxia inducible factors (HIFs) in regulating the hypoxic
      responses of hES cells. We report that culture at 20% oxygen decreased hES cell
      proliferation and resulted in a significantly reduced expression of SOX2, NANOG
      and POU5F1 (OCT4) mRNA as well as POU5F1 protein compared with hypoxic
      conditions. HIF1A protein was not expressed at 20% oxygen and displayed only a
      transient, nuclear localisation at 5% oxygen. HIF2A (EPAS1) and HIF3A displayed a
      cytoplasmic localisation during initial hypoxic culture but translocated to the
      nucleus following long-term culture at 5% oxygen and were significantly
      upregulated compared with cells cultured at 20% oxygen. Silencing of HIF2A
      resulted in a significant decrease in both hES cell proliferation and POU5F1,
      SOX2 and NANOG protein expression while the early differentiation marker, SSEA1,
      was concomitantly increased. HIF3A upregulated HIF2A and prevented HIF1A
      expression with the knockdown of HIF3A resulting in the reappearance of HIF1A
      protein. In summary, these data demonstrate that a low oxygen tension is
      preferential for the maintenance of a highly proliferative, pluripotent
      population of hES cells. While HIF3A was found to regulate the expression of both
      HIF1A and HIF2A, it is HIF2A which regulates hES cell pluripotency as well as
      proliferation under hypoxic conditions.

PMID- 19755486
TI  - On the origin of the maternal age effect in trisomy 21 Down syndrome: the Oocyte
      Mosaicism Selection model.
AB  - We have recently documented that trisomy 21 mosaicism is common in human foetal
      ovaries. On the basis of this observation we propose that the maternal age effect
      in Down syndrome (DS) is caused by the differential behaviour of trisomy 21 in
      relation to disomy 21 oocytes during development from foetal life until ovulation
      in adulthood. In particular, we suggest that trisomy 21 oocytes, lagging behind
      those that are disomic, may escape the timed pruning of the seven million in
      foetal life to the 300-400 finally selected for ovulation. The net effect of this
      preferential elimination will be an accumulation of trisomy 21 oocytes in the
      ovarian reserve of older women. We here highlight the implications of this Oocyte
      Mosaicism Selection (OMS) model with respect to the prevalent view that the
      maternal age effect is complex, dependent on many different biological and
      environmental factors. We examine conclusions drawn from recent large-scale
      studies in families, tracing DNA markers along the length of chromosome 21q
      between parents and DS children, in comparison to the OMS model. We conclude that
      these family linkage data are equally compatible with the maternal age effect
      originating from the accumulation of trisomy 21 oocytes with advancing maternal
      age. One relatively straightforward way to get to grips with what is actually
      going on in this regard would be to compare incidence of trisomy 21 oocytes (and
      their pairing configurations) in foetal ovaries with that in oocytes at the
      meiosis I stage from adult women.

PMID- 19755487
TI  - Identification of a region in the human IRS2 promoter essential for stress
      induced transcription depending on SP1, NFI binding and ERK activation in HepG2
      cells.
AB  - Recent studies have discovered changes in the insulin-/IGF1 signaling affecting
      glucose metabolism and the molecular pathogenesis of human hepatocellular cancer.
      Insulin/IGF1 receptor mediates its intracellular effects by recruitment of one
      out of the four different insulin receptor substrates (IRS). To investigate
      mechanisms of IRS2 expression, we analyzed transcriptional regulation of IRS2 in
      human HepG2 cells. We identified a region 688 bp upstream of the translation
      start codon responsible for approximately 90% of basal human IRS2 promoter
      activity in HepG2 cells, and confirmed binding of specificity protein 1 (also
      called Sp1 transcription factor, SP1) and nuclear factor 1 (NFI) in this region.
      Mutation of both SP1 and NFI binding sites or inhibition of extracellular signal
      regulated kinase (ERK) suppressed IRS2 promoter activity almost completely,
      revealing a major role of MAP kinases (MAPK) for IRS2 transcription. Activating
      this cascade with oxidative stress increased IRS2 promoter activity and
      endogenous IRS2 expression substantially. IRS2 promoter activity rose even more
      after additional inhibition of p38MAPK indicating an inhibitory effect of p38MAPK
      on ERK mediated IRS2 transcription. Activation of the MAPK pathway using
      interleukin 1, beta (IL1B) increased IRS2 promoter activity similar to oxidative
      stress. In contrast IL1B decreases and inhibition of the MAPK pathway increases
      IRS1 promoter activity revealing opposed effects of IL1B and ERK on the
      expression of different IRS proteins. In conclusion we discovered a specific
      region (-688 to -611 bp) in the IRS2 promoter essential for basal promoter
      activity and oxidative stress induced transcription depending on ERK activation
      and SP1 and NFI binding in human hepatocytes.

PMID- 19755488
TI  - How a new 'public plan' could affect hospitals' finances and private insurance
      premiums.
AB  - Two key health reform bills in the House of Representatives and Senate include
      the option of a "public plan" as an additional source of health coverage. At
      least initially, the plan would primarily be structured to cover many of the
      uninsured and those who now have individual coverage. Because it is possible, and
      perhaps even likely, that this new public payer would pay less than private
      payers for the same services, such a plan could negatively affect hospital
      margins. Hospitals may attempt to recoup losses by shifting costs to private
      payers. We outline the financial pressures that hospitals and private payers
      could experience under various assumptions. High uninsured enrollment in a public
      plan would bolster hospital margins; however, this effect is reversed if the
      privately insured enter a public plan in large proportions, potentially stressing
      the hospital industry and increasing private insurance premiums.

PMID- 19755489
TI  - Job-based health insurance: costs climb at a moderate pace.
AB  - Each year the Kaiser/HRET Survey of Employer Health Benefits takes a snapshot of
      the state of employee benefits in the United States, based on interviews with
      public and private employers. Our findings for 2009 show that families continue
      to face higher premiums, up about 5 percent from last year, and that cost sharing
      in the form of deductibles and copayments for office visits is greater as well.
      Average annual premiums in 2009 were $4,824 for single coverage and $13,375 for
      family coverage. Enrollment in high-deductible health plans held steady. We offer
      new insights about health risk assessments and how firms responded to the
      economic downturn.

PMID- 19755490
TI  - Procentriole elongation and recruitment of pericentriolar material are
      downregulated in cyst cells as they enter quiescence.
AB  - The apical region of the Drosophila testis contains a niche with two stem cell
      populations: germline stem cells (GSCs) and cyst progenitor cells (CPCs).
      Asymmetrical division of these stem cells leads to gonioblast daughters (which
      undergo further mitoses) and cyst cell daughters (which withdraw from the cell
      cycle and become quiescent). Although a considerable body of evidence indicates
      important roles for centrosomes in spindle orientation and asymmetrical division
      of GSCs, the behaviour and function of the centrioles in CPCs and their daughters
      remain unknown. Here, we show that quiescent cyst cells lose centrosome
      components after two divisions of the spermatogonia they envelop, but keep the
      centriolar component SAS-6. Cyst cells do have centriole pairs, but they are
      formed by a mother and a very short daughter that does not elongate or mature.
      The presence of procentrioles in quiescent cyst cells suggests that the centriole
      duplication cycle is uncoupled from the G1-S transition and that it might begin
      even earlier, in mitosis. Failure to enter the cell cycle might result in the
      improper recruitment of centriolar components at the mother centriole, thus
      hampering the full elongation of its daughter. Procentriole maturation defects
      could thus lead to the inability to maintain centrosomal components during
      development.

PMID- 19755491
TI  - Wif-1 is expressed at cartilage-mesenchyme interfaces and impedes Wnt3a-mediated
      inhibition of chondrogenesis.
AB  - Wnt factors are involved in the regulation of all steps of cartilage development.
      The activity of Wnt factors is generally regulated at the extracellular level by
      factors like the Dkk family, sFRPs, Cerberus and Wnt inhibitory factor 1 (Wif-1).
      Here we report that Wif-1 is highly expressed at cartilage-mesenchyme interfaces
      of the early developing skeleton. In fetal and postnatal skeletal development,
      Wif-1 is expressed in a sharply restricted zone in the upper hyaline layer of
      epiphyseal and articular cartilage and in trabecular bone. Coimmunoprecipitation
      and pull-down assays using recombinant Wif-1 and Wnt factors show specific
      binding of Wif-1 to Wnt3a, Wnt4, Wnt5a, Wnt7a, Wnt9a and Wnt11. Moreover, Wif-1
      was able to block Wnt3a-mediated activation of the canonical Wnt signalling
      pathway. Consequently, Wif-1 impaired growth of mesenchymal precursor cells and
      neutralised Wnt3a-mediated inhibition of chondrogenesis in micromass cultures of
      embryonic chick limb-bud cells. These results identify Wif-1 as a novel
      extracellular Wnt modulator in cartilage biology.

PMID- 19755492
TI  - Schizosaccharomyces pombe Cds1Chk2 regulates homologous recombination at stalled
      replication forks through the phosphorylation of recombination protein Rad60.
AB  - The Schizosaccharomyces pombe rad60 gene is essential for cell growth and is
      involved in repairing DNA double-strand breaks. Rad60 physically interacts with,
      and is functionally related to, the structural maintenance of chromosomes 5 and 6
      protein complex (Smc5/6). Rad60 is phosphorylated in response to hydroxyurea (HU)
      induced DNA replication arrest in a Cds1(Chk2)-dependent manner. Rad60 localizes
      in nucleus in unchallenged cells, but becomes diffused throughout the cell in
      response to HU. To understand the role of Rad60 phosphorylation, we mutated the
      putative phosphorylation target motifs of Cds1(Chk2) and have identified two
      Cds1(Chk2) target residues responsible for Rad60 dispersal in response to HU. We
      show that the phosphorylation-defective rad60 mutation partially suppresses HU
      sensitivity and the elevated recombination frequency of smc6-X. Our data suggest
      that Rad60 phosphorylation is required to regulate homologous recombination at
      stalled replication forks, probably by regulating Smc5/6.

PMID- 19755493
TI  - Galectin-3 promotes lamellipodia formation in epithelial cells by interacting
      with complex N-glycans on alpha3beta1 integrin.
AB  - Recent studies have shown that galectin-3 (Gal-3; also known as LGALS3), a beta
      galactoside-binding lectin, promotes cell migration during re-epithelialization
      of corneal wounds. The goal of this study was to characterize the molecular
      mechanism by which Gal-3 stimulates cell migration. We demonstrate here that
      exogenous Gal-3, but not Gal-1 or Gal-8, promotes cell scattering and formation
      of lamellipodia in human corneal epithelial cells in a beta-lactose-inhibitable
      manner. alpha3beta1 integrin was identified as the major Gal-3-binding protein in
      corneal epithelial cells by affinity chromatography of cell lysates on a Gal-3
      Sepharose column. Preincubation of cells with anti-alpha3 integrin function
      blocking antibody significantly inhibited the induction of lamellipodia by Gal-3.
      Furthermore, exogenous Gal-3 activated both focal adhesion kinase, a key
      regulator of integrin-dependent intracellular signaling, and Rac1 GTPase, a
      member of the family of Rho GTPases, well known for its role in the
      reorganization of the actin cytoskeleton and formation of lamellipodial
      extensions. Experiments involving knockdown of beta-1,6-N
      acetylglucosaminytransferase V, an enzyme that synthesizes high-affinity glycan
      ligands for Gal-3, revealed that carbohydrate-mediated interaction between Gal-3
      and complex N-glycans on alpha3beta1 integrin plays a key role in Gal-3-induced
      lamellipodia formation. We propose that Gal-3 promotes epithelial cell migration
      by cross-linking MGAT5-modified complex N-glycans on alpha3beta1 integrin and
      subsequently activating alpha3beta1-integrin-Rac1 signaling to promote
      lamellipodia formation.

PMID- 19755494
TI  - Brief report: Parent's health literacy among high-risk adolescents with insulin
      dependent diabetes.
AB  - OBJECTIVE: To describe the health literacy of parents of high-risk adolescents
      with insulin dependent diabetes and to examine the relation of parent's health
      literacy with treatment adherence. METHODS: Participants were 93 adolescents in
      poor metabolic control diagnosed with insulin dependent diabetes and their
      primary caregivers. RESULTS: All parents had adequate health literacy as defined
      by the S-TOFHLA. Better parent reading comprehension scores were significantly
      related to family structure, race, and treatment regimen. Reading comprehension
      in turn significantly predicted adherence for adolescents on an intensive insulin
      regimen but not for those on conventional regimens. CONCLUSIONS: Parents with low
      health literacy may struggle to help their children adhere to the increasingly
      complex diabetes regimens being used at present. Such families may benefit from
      more intensive diabetes education or different approaches to teaching diabetes
      management skills.

PMID- 19755495
TI  - Predictors of medication adherence in high risk youth of color living with HIV.
AB  - OBJECTIVE: To test predictors of medication adherence in high-risk racial or
      ethnic minority youth living with HIV (YLH) using a conceptual model of social
      cognitive predictors including a continuous measure of motivational readiness.
      METHODS: Youth were participants in a multi-site clinical trial examining the
      efficacy of a motivational intervention. Racial-minority YLH (primarily African
      American) who were prescribed antiretroviral medication were included (N = 104).
      Data were collected using computer-assisted personal interviewing method via an
      Internet-based application and questionnaires. RESULTS: Using path analysis with
      bootstrapping, most youth reported suboptimal adherence, which predicted higher
      viral load. Higher motivational readiness predicted optimal adherence, and higher
      social support predicted readiness. Decisional balance was indirectly related to
      adherence. CONCLUSIONS: The model provided a plausible framework for
      understanding adherence in this population. Culturally competent interventions
      focused on readiness and social support may be helpful for improving adherence in
      YLH.

PMID- 19755496
TI  - Commentary: environmental influences: issues of timing and type.

PMID- 19755497
TI  - The effectiveness of a bicycle safety program for improving safety-related
      knowledge and behavior in young elementary students.
AB  - OBJECTIVE: The purpose of this study was to evaluate the "Bike Smart" program, an
      eHealth software program that teaches bicycle safety behaviors to young children.
      METHODS: Participants were 206 elementary students in grades kindergarten to 3. A
      random control design was employed to evaluate the program, with students
      assigned to either the treatment condition (Bike Smart) or the control condition
      (a video on childhood safety). Outcome measures included computer-based knowledge
      items (safety rules, helmet placement, hazard discrimination) and a behavioral
      measure of helmet placement. RESULTS: Results demonstrated that regardless of
      gender, cohort, and grade the participants in the treatment group showed greater
      gains than control participants in both the computer-presented knowledge items (p
      > .01) and the observational helmet measure (p > .05). CONCLUSIONS: Findings
      suggest that the Bike Smart program can be a low cost, effective component of
      safety training packages that include both skills-based and experiential
      training.

PMID- 19755498
TI  - Insect tricks: two-phasic foot pad secretion prevents slipping.
AB  - Many insects cling to vertical and inverted surfaces with pads that adhere by
      nanometre-thin films of liquid secretion. This fluid is an emulsion, consisting
      of watery droplets in an oily continuous phase. The detailed function of its two
      phasic nature has remained unclear. Here we show that the pad emulsion provides a
      mechanism that prevents insects from slipping on smooth substrates. We discovered
      that it is possible to manipulate the adhesive secretion in vivo using smooth
      polyimide substrates that selectively absorb its watery component. While thick
      layers of polyimide spin-coated onto glass removed all visible hydrophilic
      droplets, thin coatings left the emulsion in its typical form. Force measurements
      of stick insect pads sliding on these substrates demonstrated that the reduction
      of the watery phase resulted in a significant decrease in friction forces.
      Artificial control pads made of polydimethylsiloxane showed no difference when
      tested on the same substrates, confirming that the effect is caused by the
      insects' fluid-based adhesive system. Our findings suggest that insect adhesive
      pads use emulsions with non-Newtonian properties, which may have been optimized
      by natural selection. Emulsions as adhesive secretions combine the benefits of
      'wet' adhesion and resistance against shear forces.

PMID- 19755499
TI  - Strategies for mitigating an influenza pandemic with pre-pandemic H5N1 vaccines.
AB  - The recent worldwide spread of the swine-origin H1N1 2009 influenza outbreak has
      resulted in its designation as a pandemic by the World Health Organization. While
      it appears to result in mild symptoms, concern still exists that a more severe
      influenza pandemic with a high case fatality ratio might arise by reassortment or
      mutation of the currently circulating avian influenza (H5N1) virus. Given that
      recently developed candidate pre-pandemic H5N1 vaccines have shown potential for
      cross-strain protection, we investigated alternative vaccination strategies that
      exploit such vaccines using an agent-based simulation model of an actual
      community of approximately 30 000 people in a developed country. Assuming that a
      two-dose vaccination regimen would be required, we examined three vaccination
      strategies: pre-emptive, with vaccination applied prior to emergence of human
      transmissible H5N1 influenza; reactive, where vaccination was initiated
      immediately after the first cases in the community were diagnosed; and a 'split'
      strategy where the first dose was administered pre-emptively during the pre
      pandemic phase, with the second dose administered reactively. We showed that by
      effectively moving the delay between first and second doses into the pre-pandemic
      period, the split vaccination strategy achieved a substantially better attack
      rate reduction than the reactive strategy. Our results for an influenza strain
      with a reproduction number of 1.5 suggest reactive vaccination strategies that
      may be applicable to the current H1N1 2009 pandemic.

PMID- 19755500
TI  - The 5'-end heterogeneity of adenovirus virus-associated RNAI contributes to the
      asymmetric guide strand incorporation into the RNA-induced silencing complex.
AB  - Human Adenovirus type 5 encodes two short RNA polymerase III transcripts, the
      virus-associated (VA) RNAI and VA RNAII, which can adopt stable hairpin
      structures that resemble micro-RNA precursors. The terminal stems of the VA RNAs
      are processed into small RNAs (mivaRNAs) that are incorporated into RISC. It has
      been reported that VA RNAI has two transcription initiation sites, which produce
      two VA RNAI species; a major species, VA RNAI(G), which accounts for 75% of the
      VA RNAI pool, and a minor species, VA RNAI(A), which initiates transcription
      three nucleotides upstream compared to VA RNAI(G). We show that this 5'
      heterogeneity results in a dramatic difference in RISC assembly. Thus, both VA
      RNAI(G) and VA RNAI(A) are processed by Dicer at the same position in the
      terminal stem generating the same 3'-strand mivaRNA. This mivaRNA is incorporated
      into RISC with 200-fold higher efficiency compared to the 5'-strand of mivaRNAI.
      Of the small number of 5'-strands used in RISC assembly only VA RNAI(A) generated
      active RISC complexes. We also show that the 3'-strand of mivaRNAI, although
      being the preferred substrate for RISC assembly, generates unstable RISC
      complexes with a low in vitro cleavage activity, only around 2% compared to RISC
      assembled on the VA RNAI(A) 5'-strand.

PMID- 19755501
TI  - Recognition of tRNAGln by Helicobacter pylori GluRS2--a tRNAGln-specific glutamyl
      tRNA synthetase.
AB  - Accurate aminoacylation of tRNAs by the aminoacyl-tRNA synthetases (aaRSs) plays
      a critical role in protein translation. However, some of the aaRSs are missing in
      many microorganisms. Helicobacter pylori does not have a glutaminyl-tRNA
      synthetase (GlnRS) but has two divergent glutamyl-tRNA synthetases: GluRS1 and
      GluRS2. Like a canonical GluRS, GluRS1 aminoacylates tRNA(Glu1) and tRNA(Glu2).
      In contrast, GluRS2 only misacylates tRNA(Gln) to form Glu-tRNA(Gln). It is not
      clear how GluRS2 achieves specific recognition of tRNA(Gln) while rejecting the
      two H. pylori tRNA(Glu) isoacceptors. Here, we show that GluRS2 recognizes major
      identity elements clustered in the tRNA(Gln) acceptor stem. Mutations in the tRNA
      anticodon or at the discriminator base had little to no impact on enzyme
      specificity and activity.

PMID- 19755502
TI  - Biophysical characterizations of human mitochondrial transcription factor A and
      its binding to tumor suppressor p53.
AB  - Human mitochondrial transcription factor A (TFAM) is a multi-functional protein,
      involved in different aspects of maintaining mitochondrial genome integrity. In
      this report, we characterized TFAM and its interaction with tumor suppressor p53
      using various biophysical methods. DNA-free TFAM is a thermally unstable protein
      that is in equilibrium between monomers and dimers. Self-association of TFAM is
      modulated by its basic C-terminal tail. The DNA-binding ability of TFAM is mainly
      contributed by its first HMG-box, while the second HMG-box has low-DNA-binding
      capability. We also obtained backbone resonance assignments from the NMR spectra
      of both HMG-boxes of TFAM. TFAM binds primarily to the N-terminal transactivation
      domain of p53, with a K(d) of 1.95 +/- 0.19 microM. The C-terminal regulatory
      domain of p53 provides a secondary binding site for TFAM. The TFAM-p53-binding
      interface involves both TAD1 and TAD2 sub-domains of p53. Helices alpha1 and
      alpha2 of the HMG-box constitute the main p53-binding region. Since both TFAM and
      p53 binds preferentially to distorted DNA, the TFAM-p53 interaction is implicated
      in DNA damage and repair. In addition, the DNA-binding mechanism of TFAM and
      biological relevance of the TFAM-p53 interaction are discussed.

PMID- 19755503
TI  - The Gene Wiki: community intelligence applied to human gene annotation.
AB  - Annotating the function of all human genes is a critical, yet formidable,
      challenge. Current gene annotation efforts focus on centralized curation
      resources, but it is increasingly clear that this approach does not scale with
      the rapid growth of the biomedical literature. The Gene Wiki utilizes an
      alternative and complementary model based on the principle of community
      intelligence. Directly integrated within the online encyclopedia, Wikipedia, the
      goal of this effort is to build a gene-specific review article for every gene in
      the human genome, where each article is collaboratively written, continuously
      updated and community reviewed. Previously, we described the creation of Gene
      Wiki 'stubs' for approximately 9000 human genes. Here, we describe ongoing
      systematic improvements to these articles to increase their utility. Moreover, we
      retrospectively examine the community usage and improvement of the Gene Wiki,
      providing evidence of a critical mass of users and editors. Gene Wiki articles
      are freely accessible within the Wikipedia web site, and additional links and
      information are available at http://en.wikipedia.org/wiki/Portal:Gene_Wiki.

PMID- 19755504
TI  - PiggyBac transgenic strategies in the developing chicken spinal cord.
AB  - The chicken spinal cord is an excellent model for the study of early neural
      development in vertebrates. However, the lack of robust, stable and versatile
      transgenic methods has limited the usefulness of chick embryos for the study of
      later neurodevelopmental events. Here we describe a new transgenic approach
      utilizing the PiggyBac (PB) transposon to facilitate analysis of late-stage
      neural development such as axon targeting and synaptic connection in the chicken
      embryo. Using PB transgenic approaches we achieved temporal and spatial
      regulation of transgene expression and performed stable RNA interference (RNAi).
      With these new capabilities, we mapped axon projection patterns of V2b subset of
      spinal interneurons and visualized maturation of the neuromuscular junction
      (NMJ). Furthermore, PB-mediated RNAi in the chick recapitulated the phenotype of
      loss of agrin function in the mouse NMJ. The simplicity and versatility of PB
      mediated transgenic strategies hold great promise for large-scale genetic
      analysis of neuronal connectivity in the chick.

PMID- 19755505
TI  - Wound Healing Activity of Rubus sanctus Schreber (Rosaceae): Preclinical Study in
      Animal Models.
AB  - Young shoots of Rubus species have been used for healing of wounds, infected
      insect bites and pimples in folk medicine for ages. In order to evaluate the
      wound healing activity of Rubus sanctus, four different extracts were prepared
      from the whole aerial parts of the plant by using n-hexane, chloroform, ethyl
      acetate and methanol, respectively. Incision wound healing model by using
      tensiometer on rats and excision model on mice were employed to assess the
      activity. Remarkable wound healing activity was observed with the ointment
      formulation of the methanol extract at 1% concentration on the mentioned models.
      The results of histopathological examination also supported the outcome of both
      incision and excision wound models. The wound healing effect was comparatively
      evaluated with a reference ointment Madecassol. The experimental data confirmed
      the ethnobotanical usage of R. sanctus.

PMID- 19755506
TI  - Hip involvement in ankylosing spondylitis: what is the verdict?

PMID- 19755507
TI  - Benefits of ultrasonography in the management of early arthritis: a cross
      sectional study of baseline data from the ESPOIR cohort.
AB  - OBJECTIVE: To assess ultrasonography's (US) performance to detect the structural
      damage in the initial evaluation of early arthritis (EA) using the Etude et
      Suivides Polyarthrites Indifferenciees Recentes (ESPOIR) cohort. METHODS: ESPOIR
      is a French, multi-centric EA cohort. Four centres assessed the structural damage
      by both X-ray and US examination at baseline. X-rays of hands and feet were read
      first by the centre's local investigator (usual reading), then in the X-ray
      coordinating centre (central reading). Four trained examiners performed US
      blindly from clinical data to detect erosions on the second and fifth MCP (MCP2
      and 5) and the fifth MTP (MTP5) joints bilaterally. RESULTS: Patients'
      characteristics (n = 126) were: female 78%; mean age 50.3 years; disease duration
      103 days; disease activity score on 28 joints 5; CRP level 22.7 mg/l; and 79.4%
      of the patients fulfilling RA ACR criteria. Twelve patients had missing data for
      X-rays. US revealed 42 (36.8%) patients with erosive disease, whereas radiography
      revealed only 30 (26%) with central reading and only 11% with usual reading. US
      missed erosive disease present in X-rays in 10 (8.8%) patients. Combined
      technique of both revealed 52 (45.6%) patients with erosive diseases. On the
      targeted joints, US detected erosion on 75 (11%) joints vs X-rays on only 11
      (1.5%). Only three joints with erosion(s) detected on X-rays were missed on US.
      At baseline, the presence of PD activity was not associated with joint erosions.
      CONCLUSIONS: US on six joints detected 1.4-fold more patients with erosions (3.3
      fold more with the usual reading). In clinical practice, US combined with X-rays
      is of helpful diagnostic value in EA.

PMID- 19755508
TI  - Inflammatory profile in the cerebrospinal fluid of patients with central
      neuropsychiatric lupus, with and without associated factors.

PMID- 19755509
TI  - Combination of EGFR and MEK1/2 inhibitor shows synergistic effects by suppressing
      EGFR/HER3-dependent AKT activation in human gastric cancer cells.
AB  - EGFR tyrosine kinase inhibitors have shown promising efficacy in the treatment of
      tumors with EGFR mutations and amplifications. However, tyrosine kinase
      inhibitors have also proven ineffective against most tumors with EGFR wild-type
      (WT) alleles. Although some genetic changes, including the KRAS mutation, have
      been shown to confer resistance to tyrosine kinase inhibitors, novel strategies
      for the treatment of cancer patients with tumors harboring EGFR WT alleles have
      yet to be thoroughly delineated. The principal objective of this study was to
      improve our current understanding of drug interactions between EGFR and MAP/ERK
      kinase (MEK) inhibitors in an effort to gain insight into a novel therapeutic
      strategy against EGFR WT tumors. Using a panel of human EGFR WT gastric cancer
      cell lines, we showed that gastric cancer cells harboring the KRAS mutation were
      selectively sensitive to MEK inhibition as compared with those cells harboring
      KRAS and PI3K mutations and KRAS WT alleles. However, all cell lines were found
      to be resistant to EGFR inhibition. The results from Western blots and
      phosphoprotein arrays showed that, in MEK inhibitor resistant cell lines, AKT was
      activated through the EGFR/HER3/PI3K pathway following AZD6244 (ARRY-142886)
      treatment. Blockade of this feedback mechanism through the targeting of MEK and
      EGFR resulted in detectable synergistic effects in some cell lines in vitro and
      in vivo. Our results provide the basis for a rational combination strategy
      against human EGFR WT gastric cancers, predicated on the understanding of cross
      talk between the MEK and EGFR pathways.

PMID- 19755510
TI  - Targeting vascular endothelial growth factor receptor-1 and -3 with cediranib
      (AZD2171): effects on migration and invasion of gastrointestinal cancer cell
      lines.
AB  - The effect of vascular endothelial growth factor (VEGF) ligands and cediranib on
      tumor cell proliferation, migration, and invasion was determined. It has recently
      been suggested that autocrine signaling through the VEGF receptor (VEGFR) pathway
      may play a role in tumor cell survival, invasion, and migration. The purpose of
      the present study was to determine the expression of VEGFRs and VEGFR ligands in
      a panel of gastrointestinal carcinoma cells. Additionally, we evaluated the
      effects of VEGF autocrine signaling on tumor cell proliferation, migration, and
      invasion utilizing cediranib (AZD2171), a pan-VEGFR inhibitor. Five colorectal,
      three pancreatic, and two hepatocellular carcinoma cell lines were screened for
      VEGFR and VEGF expression by several methods. Expression of VEGFR-1 and VEGFR-3
      was cell line-dependent, whereas VEGFR-2 was not detected. Secretion of VEGF-A
      was detected in the supernatants of all cell lines whereas VEGF-C secretion was
      detected in the Panc-1, MiaPaca2, and Hep1 cells only. Tumor cells showed
      increased migratory activity, but not proliferation, when stimulated with VEGFs.
      The pan-VEGFR inhibitor cediranib (100 nmol/L) inhibited tumor cell migration and
      invasion, with no effects on proliferation. Cediranib decreased VEGFR-1 and VEGFR
      3 phosphorylation as well as activation of downstream effectors. VEGFR-1 and
      VEGFR-3 expression was detected in all the gastrointestinal carcinoma cells
      evaluated. Although activation of the VEGF pathway did not affect cell
      proliferation, our data indicate that this pathway seems to play a role in tumor
      cell migration and invasion in these cell lines. Therefore, inhibition of VEGFR
      by cediranib may represent a clinically relevant treatment option for
      gastrointestinal tumors.

PMID- 19755511
TI  - The role of vascular endothelial growth factor SNPs as predictive and prognostic
      markers for major solid tumors.
AB  - Angiogenesis is crucial for development and metastasis of tumors, and vascular
      endothelial growth factor (VEGF) is a key mediator of this process. The
      importance of VEGF in tumorigenesis and tumor progression makes it an attractive
      target for the development of anticancer therapies. Inhibition of angiogenesis
      has shown promising clinical efficacy; however, not all patients treated with
      antiangiogenic agents derive benefit from them. Some patients are predisposed to
      refractory disease, whereas others develop resistance after initial response.
      Patients may also have different severity of drug-related adverse events.
      Optimization of drug administration based on disease status and individual
      responsiveness is important in limiting the treatment failure and minimization of
      side-effects. Single nucleotide polymorphisms (SNP) in VEGF may alter VEGF
      protein concentrations, influence the process of angiogenesis, and may relate to
      interindividual variation in the risk and progression of selected tumors, and
      their resistance to treatments. This review examines the role of SNPs in the VEGF
      gene as predictive and prognostic markers for major solid tumors, including the
      breast, non-small cell lung, colorectal, and prostate cancers. Selected VEGF SNPs
      seem to be associated with risk of these cancers; however, there is lack of
      unanimity in findings, in part influenced by differences in study design and
      analysis.

PMID- 19755512
TI  - Preclinical biomarkers for a cyclin-dependent kinase inhibitor translate to
      candidate pharmacodynamic biomarkers in phase I patients.
AB  - A genomics-based approach to identify pharmacodynamic biomarkers was used for a
      cyclin-dependent kinase inhibitory drug. R547 is a potent cyclin-dependent kinase
      inhibitor with a potent antiproliferative effect at pharmacologically relevant
      doses and is currently in phase I clinical trials. Using preclinical data derived
      from microarray experiments, we identified pharmacodynamic biomarkers to test in
      blood samples from patients in clinical trials. These candidate biomarkers were
      chosen based on several criteria: relevance to the mechanism of action of R547,
      dose responsiveness in preclinical models, and measurable expression in blood
      samples. We identified 26 potential biomarkers of R547 action and tested their
      clinical validity in patient blood samples by quantitative real-time PCR
      analysis. Based on the results, eight genes (FLJ44342, CD86, EGR1, MKI67, CCNB1,
      JUN, HEXIM1, and PFAAP5) were selected as dose-responsive pharmacodynamic
      biomarkers for phase II clinical trials.

PMID- 19755513
TI  - A novel small molecule with potent anticancer activity inhibits cell growth by
      modulating intracellular labile zinc homeostasis.
AB  - ML-133 is a novel small molecule with potent antiproliferative activity, as shown
      in cancer cell lines and in a human colon tumor xenograft model. ML-133 reduces
      the concentration of intracellular labile zinc in HT-29 colon cancer cells,
      leading to induction of the Kruppel-like factor 4 transcription factor. Kruppel
      like factor 4 displaces the positive regulator SP1 from the cyclin D1 promoter,
      thereby negatively regulating the expression of cyclin D1 and promoting the G(1)
      S phase arrest of cell proliferation. The antiproliferative and antitumor
      activity of ML-133 described in the present study suggests modulation of
      intracellular zinc homeostasis as a potential strategy for the treatment of
      several cancer types, and ML-133 represents a promising new class of antitumor
      agents that deserves further development.

PMID- 19755514
TI  - Tumor necrosis factor deficiency inhibits mammary tumorigenesis and a tumor
      necrosis factor neutralizing antibody decreases mammary tumor growth in neu/erbB2
      transgenic mice.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a pleiotropic cytokine that is
      synthesized and secreted by cells of the immune system, as well as by certain
      epithelia and stroma. Based on our previous studies demonstrating TNF-stimulated
      proliferation of normal and malignant mammary epithelial cells, we hypothesized
      that TNF might promote the growth of breast cancer in vivo. To test this, we
      generated bigenic mice that overexpressed activated neu/erbB2 in the mammary
      epithelium and whose TNF status was wild-type, heterozygous, or null. Mammary
      tumorigenesis was significantly decreased in TNF-/- mice (n = 30) compared with
      that in TNF+/+ mice (n = 27), with a palpable tumor incidence of 10.0% and 44.4%,
      and palpable tumors/mouse of 0.10 +/- 0.06 and 0.67 +/- 0.17, respectively.
      Tumorigenesis in the heterozygous group fell between that in the TNF+/+ and TNF-/
      groups, but was not significantly different from either of the homozygous
      groups. The decreased tumor development in the TNF-/- mice was associated with a
      decreased proliferative index in the lobular and ductal mammary epithelium. To
      further investigate the role of TNF in breast cancer, mammary tumor-bearing mice
      whose tumors overexpressed wild-type neu/erbB2 were treated with a TNF
      neutralizing antibody or a control antibody for 4 weeks (n = 20/group). Mammary
      tumor growth was significantly inhibited in mice treated with the anti-TNF
      antibody compared with the control antibody. Together, these data show a
      stimulatory role for TNF in the growth of breast tumors and suggest that TNF
      antagonists may be effective in a subset of patients with breast cancer.

PMID- 19755515
TI  - Celecoxib antagonizes perifosine's anticancer activity involving a cyclooxygenase
      2-dependent mechanism.
AB  - Perifosine is an orally bioavailable alkylphospholipid currently being tested in
      phase II clinical trials as a potential anticancer drug. In this study, we reveal
      a novel mechanism underlying the anticancer activity of perifosine that involves
      the induction of cyclooxygenase 2 (COX-2) in human cancer cells. Perifosine
      induced apoptosis and/or cell cycle arrest in several lung and head and neck
      cancer cell lines. However, the combination of perifosine with low concentrations
      of celecoxib rendered cells less sensitive to perifosine both in cell culture
      systems and in lung cancer xenograft models. Subsequently, we examined the
      effects of perifosine on COX-2 expression and activity in a set of lung and head
      and neck cancer cell lines, and found that perifosine rapidly and potently
      increased COX-2 levels and activity, the degrees of which correlated to the
      abilities of perifosine to inhibit the growth of cancer cells. We also detected
      increased COX-2 levels in lung cancer xenografts treated with perifosine.
      Moreover, blockage of COX-2 induction by both antisense and small interfering RNA
      approaches decreased cell sensitivity to perifosine. Collectively, these data
      indicate that the activation of COX-2 contributes to the anticancer activity of
      perifosine, including apoptosis induction and growth arrest. These data are
      clinically relevant as they suggest that the combination of perifosine and COX-2
      inhibitors such as celecoxib, may produce a potential drug contradiction.

PMID- 19755516
TI  - Anticancer activity of targeted proapoptotic peptides and chemotherapy is highly
      improved by targeted cell surface calreticulin-inducer peptides.
AB  - We have recently identified (a) ectocalreticulin as the main source of
      immunogenicity of cancer cell death induced by chemotherapy or radiotherapy, (b)
      ectoERP57 as critical protein for inducing cell surface exposure of calreticulin,
      and (c) that ectoERP57 and ectocalreticulin are cotranslocated together to the
      tumor cell surface by the mediator of the inhibition of PP1/GADD34 complex. Here,
      I report that the immunogenicity of cancer cell death induced by anticancer
      targeted proapoptotic peptides is also dictated by ectocalreticulin. To improve
      the anticancer activity of these proapoptotic peptides, I have designed several
      targeted chimeric inhibitor peptides of the PP1/GADD34 complex, which are
      comprised of an inhibitor peptide of the PP1/GADD34 complex fused to a protein
      transduction domain-5, to prostate homing peptide, or to the tumor antigen
      BiP/GRP78-binding peptide motifs. These inhibitor peptides (a) induce
      ectocalreticulin and ectoERP57 in a variety of tumor cell lines by the mediator
      of the inhibition of the interaction between PP1 and GADD34, (b) increase the
      phagocytosis of anticancer targeted proapoptotic peptide-treated tumor cells by
      dendritic cells, and (c) improve highly the anticancer activity of proapoptotic
      peptides and chemotherapy by suppressing or reducing the tumor growth in several
      isogenic mouse models of colon, mammary, and fibrosarcoma tumors and by
      increasing the lifespan of transgenic adenocarcinoma mouse prostate mice. These
      results suggest (a) that the inhibition of PP1/GADD34 complex is a key element to
      improve the anticancer activity of targeted proapoptotic peptides and
      chemotherapy and (b) that these targeted peptides combination approach could
      serve as a new powerful autonomous anticancer therapy.

PMID- 19755517
TI  - C. elegans dysferlin homolog fer-1 is expressed in muscle, and fer-1 mutations
      initiate altered gene expression of muscle enriched genes.
AB  - Mutations in the human dysferlin gene cause Limb Girdle Muscular Dystrophy 2B
      (LGMD2B). The Caenorhabditis elegans dysferlin homolog, fer-1, affects sperms
      development but is not known to be expressed in or have a functional roles
      outside of the male germline. Using several approaches, we show that fer-1 mRNA
      is present in C. elegans muscle cells but is absent from neurons. In mammals,
      loss of muscle-expressed dysferlin causes transcriptional deregulation of muscle
      expressed genes. To determine if similar alterations in gene expression are
      initiated in C. elegans due to loss of muscle-expressed fer-1, we performed whole
      genome Affymetrix microarray analysis of two loss-of-function fer-1 mutants. Both
      mutants gave rise to highly similar changes in gene expression and altered the
      expression of 337 genes. Using multiple analysis methods, we show that this gene
      set is enriched for genes known to regulate the structure and function of muscle.
      However, these transcriptional changes do not appear to be in response to gross
      sarcomeric damage, since genetically sensitized fer-1 mutants exhibit normal thin
      filament organization. Our data suggest that processes other than sarcomere
      stability may be affected by loss of fer-1 in C. elegans muscle. Therefore, C.
      elegans may be an attractive model system in which to explore new muscle-specific
      functions of the dysferlin protein and gain insights into the molecular
      pathogenesis of LGMD2B.

PMID- 19755518
TI  - Impaired visual processing preceding image recognition in Parkinson's disease
      patients with visual hallucinations.
AB  - Impaired visual processing may play a role in the pathophysiology of visual
      hallucinations in Parkinson's disease. In order to study involved neuronal
      circuitry, we assessed cerebral activation patterns both before and during
      recognition of gradually revealed images in Parkinson's disease patients with
      visual hallucinations (PDwithVHs), Parkinson's disease patients without visual
      hallucinations (PDnonVHs) and healthy controls. We hypothesized that, before
      image recognition, PDwithVHs would show reduced bottom-up visual activation in
      occipital-temporal areas and increased (pre)frontal activation, reflecting
      increased top-down demand. Overshoot of the latter has been proposed to play a
      role in generating visual hallucinations. Nine non-demented PDwithVHs, 14
      PDnonVHs and 13 healthy controls were scanned on a 3 Tesla magnetic resonance
      imaging scanner. Static images of animals and objects gradually appearing out of
      random visual noise were used in an event-related design paradigm. Analyses were
      time-locked on the moment of image recognition, indicated by the subjects' button
      press. Subjects were asked to press an additional button on a colour-changing
      fixation dot, to keep attention and motor action constant and to assess reaction
      times. Data pre-processing and statistical analysis were performed with
      statistical parametric mapping-5 software. Bilateral activation of the fusiform
      and lingual gyri was seen during image recognition in all groups (P < 0.001).
      Several seconds before image recognition, PDwithVHs showed reduced activation of
      the lateral occipital cortex, compared with both PDnonVHs and healthy controls.
      In addition, reduced activation of extrastriate temporal visual cortices was seen
      just before image recognition in PDwithVHs. The association between increased
      vulnerability for visual hallucinations in Parkinson's disease and impaired
      visual object processing in occipital and temporal extrastriate visual cortices
      supported the hypothesis of impaired bottom-up visual processing in PDwithVHs.
      Support for the hypothesized increased top-down frontal activation was not
      obtained. The finding of activation reductions in ventral/lateral visual
      association cortices in PDwithVHs before image recognition further helps to
      explain functional mechanisms underlying visual hallucinations in Parkinson's
      disease.

PMID- 19755519
TI  - Functional definition of seizure provides new insight into post-traumatic
      epileptogenesis.
AB  - Experimental animals' seizures are often defined arbitrarily based on duration,
      which may lead to misjudgement of the syndrome and failure to develop a cure. We
      employed a functional definition of seizures based on the clinical practice of
      observing epileptiform electrocorticography and simultaneous ictal behaviour, and
      examined post-traumatic epilepsy induced in rats by rostral parasagittal fluid
      percussion injury and epilepsy patients evaluated with invasive monitoring. We
      showed previously that rostral parasagittal fluid percussion injury induces
      different types of chronic recurrent spontaneous partial seizures that worsen in
      frequency and duration over the months post injury. However, a remarkable feature
      of rostral parasagittal fluid percussion injury is the occurrence, in the early
      months post injury, of brief (<2 s) focal, recurrent and spontaneous epileptiform
      electrocorticography events (EEEs) that are never observed in sham-injured
      animals and have electrographic appearance similar to the onset of obvious
      chronic recurrent spontaneous partial seizures. Simultaneous epidural
      electrocorticography and scalp-electroencephalography recordings in the rat
      demonstrated that these short EEEs are undetectable by scalp
      electrocorticography. Behavioural analysis performed blinded to the
      electrocorticography revealed that (i) brief EEEs lasting 0.8-2 s occur
      simultaneously with behavioural arrest; and (ii) while behavioural arrest is part
      of the rat's behavioural repertoire, the probability of behavioural arrest is
      greatly elevated during EEEs. Moreover, spectral analysis showed that EEEs
      lasting 0.8-2 s occurring during periods of active behaviour with dominant theta
      activity are immediately followed by loss of such theta activity. We thus
      conclude that EEEs lasting 0.8-2 s are ictal in the rat. We demonstrate that the
      assessment of the time course of fluid percussion injury-induced epileptogenesis
      is dramatically biased by the definition of seizure employed, with common
      duration-based arbitrary definitions resulting in artificially prolonged
      latencies for epileptogenesis. Finally, we present four human examples of
      electrocorticography capturing short (<2 s), stereotyped, neocortically generated
      EEEs that occurred in the same ictal sites as obvious complex partial seizures,
      were electrographically similar to rat EEEs and were not noted during scalp
      electroencephalography. When occurring in the motor cortex, these short EEEs were
      accompanied by ictal behaviour detectable with simultaneous surface
      electromyography. These data demonstrate that short (<2 s) focal recurrent
      spontaneous EEEs are seizures in both rats and humans, that they are undetectable
      by scalp electroencephalography, and that they are typically associated with
      subtle and easily missed behavioural correlates. These findings define the
      earliest identifiable markers of progressive post-traumatic epilepsy in the rat,
      with implications for mechanistic and prophylactic studies, and should prompt a
      re-evaluation of the concept of post-traumatic silent period in both animals and
      humans.

PMID- 19755520
TI  - Magnetic resonance diagnostic markers in clinically sporadic prion disease: a
      combined brain magnetic resonance imaging and spectroscopy study.
AB  - The intra vitam diagnosis of prion disease is challenging and a definite
      diagnosis still requires neuropathological examination in non-familial cases.
      Magnetic resonance imaging has gained increasing importance in the diagnosis of
      prion disease. The aim of this study was to compare the usefulness of different
      magnetic resonance imaging sequences and proton magnetic resonance spectroscopy
      in the differential diagnosis of patients with rapidly progressive neurological
      signs compatible with the clinical diagnosis of sporadic prion disease. Twenty
      nine consecutive patients with an initial diagnosis of possible or probable
      sporadic prion disease, on the basis of clinical and electroencephalography
      features, were recruited. The magnetic resonance protocol included axial fluid
      attenuated inversion recovery-T2- and diffusion-weighted images, and proton
      magnetic resonance spectroscopy of the thalamus, striatum, cerebellum and
      occipital cortex. Based on the clinical follow-up, genetic studies and
      neuropathology, the final diagnosis was of prion disease in 14 patients out of
      29. The percentage of correctly diagnosed cases was 86% for diffusion-weighted
      imaging (hyperintensity in the striatum/cerebral cortex), 86% for thalamic N
      acetyl-aspartate to creatine ratio (cutoff </=1.21), 90% for thalamic N-acetyl
      aspartate to myo-inositol (mI) ratio (cutoff </=1.05) and 86% for cerebral spinal
      fluid 14-3-3 protein. All the prion disease patients had N-acetyl-aspartate to
      creatine ratios </=1.21 (100% sensitivity and 100% negative predictive value) and
      all the non-prion patients had N-acetyl-aspartate to myo-inositol ratios >1.05
      (100% specificity and 100% positive predictive value). Univariate logistic
      regression analysis showed that the combination of thalamic N-acetyl-aspartate to
      creatine ratio and diffusion-weighted imaging correctly classified 93% of the
      patients. The combination of thalamic proton magnetic resonance spectroscopy (10
      min acquisition duration) and brain diffusion-weighted imaging (2 min acquisition
      duration) may increase the diagnostic accuracy of the magnetic resonance scan.
      Both sequences should be routinely included in the clinical work-up of patients
      with suspected prion disease.

PMID- 19755521
TI  - Urotensin II induces rat cardiomyocyte hypertrophy via the transient oxidization
      of Src homology 2-containing tyrosine phosphatase and transactivation of
      epidermal growth factor receptor.
AB  - Urotensin II (U-II) is implicated in cardiomyocyte hypertrophy, which results in
      cardiac remodeling. We recently demonstrated that both reactive oxygen species
      (ROS) generation and epidermal growth factor receptor (EGFR) transactivation play
      critical roles in U-II signal transduction. However, the detailed intracellular
      mechanism(s) underlying cardiac hypertrophy and remodeling remain unclear. In
      this study, we used rat cardiomyocytes treated with U-II to investigate the
      association between ROS generation and EGFR transactivation. U-II treatment was
      found to stimulate cardiomyocyte hypertrophy through phosphorylation of EGFR and
      ROS generation. Apocynin, an NAD(P)H oxidase inhibitor, and N-acetyl cysteine
      (NAC), an ROS scavenger, both inhibited EGFR transactivation induced by U-II. In
      contrast, 4-(3'-chloroanilino)-6,7-dimethoxy-quinazoline (AG1478, an EGFR
      inhibitor) failed to inhibit intracellular ROS generation induced by U-II. Src
      homology 2-containing tyrosine phosphatase (SHP-2), but not protein tyrosine
      phosphatase 1B (PTP 1B), was shown to be associated with EGFR during U-II
      treatment by EGFR coimmunoprecipitation. ROS have been reported to transiently
      oxidize the catalytic cysteine of phosphotyrosine phosphatases, subsequently
      inhibiting their activity. We examined the effect of U-II on SHP-2 and PTP 1B in
      cardiomyocytes using a modified malachite green phosphatase assay. SHP-2, but not
      PTP 1B, was transiently oxidized during U-II treatment, which could be repressed
      by NAC treatment. In SHP-2 knockdown cells, U-II-induced phosphorylation of EGFR
      and myocyte hypertrophy were dramatically elevated, and these effects were not
      influenced by NAC. Our data suggest that U-II-mediated ROS generation can
      transiently inhibit SHP-2 activity, thereby facilitating EGFR transactivation and
      hypertrophic signal transduction in rat cardiomyocytes.

PMID- 19755522
TI  - Subtype-specific differences in corticotropin-releasing factor receptor complexes
      detected by fluorescence spectroscopy.
AB  - G protein-coupled receptors have been proposed to exist in signalosomes subject
      to agonist-driven shifts in the assembly disassembly equilibrium, affected by
      stabilizing membrane lipids and/or cortical actin restricting mobility. We
      investigated the highly homologous corticotropin-releasing factor receptors
      (CRFRs), CRFR1 and -2, which are different within their hydrophobic core. Agonist
      stimulation of CRFR1 and CRFR2 gave rise to similar concentration-response curves
      for cAMP accumulation, but CRFR2 underwent restricted collision coupling. Both
      CRFR1 and CRFR2 formed constitutive oligomers at the cell surface and recruited
      beta-arrestin upon agonist activation (as assessed by fluorescence resonance
      energy transfer microscopy in living cells). However, CRFR2, but not CRFR1,
      failed to undergo agonist-induced internalization. Likewise, agonist binding
      accelerated the diffusion rate of CRFR2 only (detected by fluorescence recovery
      after photobleaching and fluorescence correlation spectroscopy) but reduced the
      mobile fraction, which is indicative of local confinement. Fluorescence intensity
      distribution analysis demonstrated that the size of CRFR complexes was not
      changed. Disruption of the actin cytoskeleton abolished the agonist-dependent
      increase in CRFR2 mobility, shifted the agonist concentration curve for CRFR2 to
      the left, and promoted agonist-induced internalization of CRFR2. Our observations
      are incompatible with an agonist-induced change in monomer-oligomer equilibrium,
      but they suggest an agonist-induced redistribution of CRFR2 into a membrane
      microdomain that affords rapid diffusion but restricted mobility and that is
      stabilized by the actin cytoskeleton. Our data show that membrane anisotropy can
      determine the shape and duration of receptor-generated signals in a subtype
      specific manner.

PMID- 19755523
TI  - Dysregulation of secretion of CXC alpha-chemokine CXCL10 in papillary thyroid
      cancer: modulation by peroxisome proliferator-activated receptor-gamma agonists.
AB  - In papillary thyroid carcinomas (PTCs), oncogenes activate a transcriptional
      program including the upregulation of CXCL10 chemokine, which stimulates
      proliferation and invasion. Furthermore, peroxisome proliferator-activated
      receptor-gamma (PPARgamma) activators thiazolidinediones (TZDs) modulate CXCL10
      secretion in normal thyroid follicular cells (TFC), and inhibit PTC growth. Until
      now, no study has evaluated the effect of cytokines on CXCL10 secretion in PTCs,
      nor the effect of PPARgamma activation. The combined effects of interferon gamma
      (IFNgamma) and tumor necrosis factor alpha (TNFalpha) stimulation on CXCL10
      secretion in primary cells from PTCs and TFC were tested. Furthermore, the effect
      of PPARgamma activation by TZDs, on CXCL10 secretion and proliferation in these
      cell types was studied. In primary cultures of TFC and PTCs CXCL10 production was
      absent under basal conditions; a similar dose-dependent secretion of CXCL10 was
      induced by IFNgamma in both cell types. TNFalpha alone induced a slight but
      significant CXCL10 secretion only in PTCs. The stimulation with IFNgamma+TNFalpha
      induced a synergistic CXCL10 release in both cell types; however, a secretion
      more than ten times higher was induced in PTCs. Treatment of TFC with TZDs dose
      dependently suppressed IFNgamma+TNFalpha-induced CXCL10 release, while TZDs
      stimulated CXCL10 secretion in PTCs. A significant antiproliferative effect by
      TZDs was observed only in PTCs. In conclusion, a dysregulation of CXCL10
      secretion has been shown in PTCs. In fact, a CXCL10 secretion more than ten times
      higher has been induced by IFNgamma+TNFalpha in PTCs with respect to TFC.
      Moreover, TZDs inhibited CXCL10 secretion in TFC and stimulated it in PTCs. The
      effect of TZDs on CXCL10 was unrelated to the significant antiproliferative
      effect in PTCs.

PMID- 19755524
TI  - Beta-catenin activation is not involved in sporadic parathyroid carcinomas and
      adenomas.
AB  - Aberrant accumulation of beta-catenin has been found in various types of human
      tumors. The aim of this study was to evaluate whether Wnt/beta-catenin signaling
      is activated in parathyroid carcinomas and adenomas. We studied 154 parathyroid
      tumors (18 carcinomas (13 with distant metastases), six atypical adenomas, and
      130 adenomas). Three normal parathyroid tissues were used as control. Direct
      sequencing of exon 3 of the CTNNB1 gene showed absence of stabilizing mutations
      in all the tumors. Immunostaining of beta-catenin was performed in all carcinomas
      and in 66 adenomas (including three atypical). Normal parathyroid showed a
      homogeneous distinct outer cell membrane staining in the majority of cells and no
      nuclear staining. A weak cytoplasmic staining was observed in one case. All
      tumors showed negative nuclear staining. With the exception of one carcinoma,
      which had a negative membrane staining, all other samples showed a membrane
      staining which was similar to that of the normal parathyroid. beta-Catenin
      expression was heterogeneous with a range of positive cells between 5 and 80%,
      independently of tumor type. Our results suggest that the Wnt/beta-catenin
      signaling pathway is not involved in the development of parathyroid carcinomas
      and adenomas.

PMID- 19755525
TI  - Endoplasmic reticulum stress in diabetic hearts abolishes erythropoietin-induced
      myocardial protection by impairment of phospho-glycogen synthase kinase-3beta
      mediated suppression of mitochondrial permeability transition.
AB  - OBJECTIVE: Alteration in endoplasmic reticulum (ER) stress in diabetic hearts and
      its effect on cytoprotective signaling are unclear. Here, we examine the
      hypothesis that ER stress in diabetic hearts impairs phospho-glycogen synthase
      kinase (GSK)-3beta-mediated suppression of mitochondrial permeability transition
      pore (mPTP) opening, compromising myocardial response to cytoprotective
      signaling. RESEARCH DESIGN AND METHODS: A rat model of type 2 diabetes (OLETF)
      and its control (LETO) were treated with tauroursodeoxycholic acid (TUDCA) (100
      mg . kg(-1) . day(-1) for 7 days), an ER stress modulator. Infarction was induced
      by 20-min coronary occlusion and 2-h reperfusion. RESULTS: Levels of ER
      chaperones (GRP78 and GRP94) in the myocardium and level of nonphoshopho-GSK
      3beta in the mitochondria were significantly higher in OLETF than in LETO rats.
      TUDCA normalized levels of GRP78 and GRP94 and mitochondrial GSK-3beta in OLETF
      rats. Administration of erythropoietin (EPO) induced phosphorylation of Akt and
      GSK-3beta and reduced infarct size (% risk area) from 47.4 +/- 5.2% to 23.9 +/-
      3.5% in LETO hearts. However, neither phosphorylation of Akt and GSK-3beta nor
      infarct size limitation was induced by EPO in OLETF rats. The threshold for mPTP
      opening was significantly lower in mitochondria from EPO-treated OLETF rats than
      in those from EPO-treated LETO rats. TUDCA restored responses of GSK-3beta, mPTP
      opening threshold, and infarct size to EPO receptor activation in OLETF rats.
      There was a significant correlation between mPTP opening threshold and phospho
      GSK-3beta-to-total GSK-3beta ratio in the mitochondrial fraction. CONCLUSIONS:
      Disruption of protective signals leading to GSK-3beta phosphorylation and
      increase in mitochondrial GSK-3beta are dual mechanisms by which increased ER
      stress inhibits EPO-induced suppression of mPTP opening and cardioprotection in
      diabetic hearts.

PMID- 19755526
TI  - Predictive characteristics of diabetes-associated autoantibodies among children
      with HLA-conferred disease susceptibility in the general population.
AB  - OBJECTIVE: As data on the predictive characteristics of diabetes-associated
      autoantibodies for type 1 diabetes in the general population are scarce, we
      assessed the predictive performance of islet cell autoantibodies (ICAs) in
      combination with autoantibodies against insulin (IAAs), autoantibodies against
      GAD, and/or islet antigen 2 for type 1 diabetes in children with HLA-defined
      disease predisposition recruited from the general population. RESEARCH DESIGN AND
      METHODS: We observed 7,410 children from birth (median 9.2 years) for beta-cell
      autoimmunity and diabetes. If a child developed ICA positivity or diabetes, the
      three other antibodies were measured in all samples available from that
      individual. Persistent autoantibody positivity was defined as continued
      positivity in at least two sequential samples including the last available
      sample. RESULTS: Pre-diabetic ICA positivity was observed in 1,173 subjects
      (15.8%), 155 of whom developed type 1 diabetes. With ICA screening, 86% of 180
      progressors (median age at diagnosis 5.0 years) were identified. Positivity for
      four antibodies was associated with the highest disease sensitivity (54.4%) and
      negative predictive values (98.3%) and the lowest negative likelihood ratio
      (0.5). The combination of persistent ICA and IAA positivity resulted in the
      highest positive predictive value (91.7%), positive likelihood ratio (441.8),
      cumulative disease risk (100%), and specificity (100%). Young age at
      seroconversion, high ICA level, multipositivity, and persistent positivity for
      IAA were significant risk markers for type 1 diabetes. CONCLUSIONS: Within the
      general population, the combination of HLA and autoantibody screening resulted in
      disease risks that are likely to be as high as those reported among autoantibody
      positive siblings of children with type 1 diabetes.

PMID- 19755527
TI  - Effects of insulin on the metabolic control of hepatic gluconeogenesis in vivo.
AB  - OBJECTIVE: Insulin represses the expression of gluconeogenic genes at the mRNA
      level, but the hormone appears to have only weak inhibitory effects in vivo. The
      aims of this study were 1) to determine the maximal physiologic effect of
      insulin, 2) to determine the relative importance of its effects on gluconeogenic
      regulatory sites, and 3) to correlate those changes with alterations at the
      cellular level. RESEARCH DESIGN AND METHODS: Conscious 60-h fasted canines were
      studied at three insulin levels (near basal, 4x, or 16x) during a 5-h euglycemic
      clamp. Pancreatic hormones were controlled using somatostatin with portal insulin
      and glucagon infusions. Glucose metabolism was assessed using the arteriovenous
      difference technique, and molecular signals were assessed. RESULTS: Insulin
      reduced gluconeogenic flux to glucose-6-phosphate (G6P) but only at the near
      maximal physiological level (16x basal). The effect was modest compared with its
      inhibitory effect on net hepatic glycogenolysis, occurred within 30 min, and was
      associated with a marked decrease in hepatic fat oxidation, increased liver
      fructose 2,6-bisphosphate level, and reductions in lactate, glycerol, and amino
      acid extraction. No further diminution in gluconeogenic flux to G6P occurred over
      the remaining 4.5 h of the study, despite a marked decrease in PEPCK content,
      suggesting poor control strength for this enzyme in gluconeogenic regulation in
      canines. CONCLUSIONS: Gluconeogenic flux can be rapidly inhibited by high insulin
      levels in canines. Initially decreased hepatic lactate extraction is important,
      and later reduced gluconeogenic precursor availability plays a role. Changes in
      PEPCK appear to have little or no acute effect on gluconeogenic flux.

PMID- 19755528
TI  - Tumor necrosis factor-alpha does not mediate diabetes-induced vascular
      inflammation in mice.
AB  - OBJECTIVE: Vascular inflammation is a key feature of both micro- and
      macrovascular complications in diabetes. Several lines of evidence have
      implicated the cytokine tumor necrosis factor (TNF) alpha as an important
      mediator of inflammation in diabetes. In the present study we evaluated the role
      of TNF alpha in streptozotocin (STZ)-induced diabetes on vascular inflammation in
      C57BL/6 wild-type and apoE-/- mice. METHODS AND RESULTS: Diabetes increased the
      expression of vascular cell adhesion molecule (VCAM)-1 in cerebral arteries 150 m
      in diameter as well as the macrophage accumulation in aortic root atherosclerotic
      plaques in apoE-/- mice. A more pronounced vascular inflammatory response was
      observed in diabetic TNF alpha-deficient apoE-/- mice. These mice were also
      characterized by increased accumulation of IgG and IgM autoantibodies in
      atherosclerotic lesions. Diabetes also increased VCAM-1 expression and plaque
      formation in apoE-competent TNF alpha -/- mice, whereas no such effects were
      observed in C57BL/6 wild-type mice. CONCLUSIONS: The present findings suggest
      that TNF alpha does not mediate diabetic-induced vascular inflammation in mice
      and reveal an unexpected protective role for TNF alpha. These effects are partly
      attributable to a direct antiinflammatory role of TNF alpha, but may also reflect
      a defective development of the immune system in these mice.

PMID- 19755529
TI  - Females prefer to associate with males with longer intromittent organs in
      mosquitofish.
AB  - Sexual selection is a major force behind the rapid evolution of male genital
      morphology among species. Most within-species studies have focused on sexual
      selection on male genital traits owing to events during or after copulation that
      increase a male's share of paternity. Very little attention has been given to
      whether genitalia are visual signals that cause males to vary in their
      attractiveness to females and are therefore under pre-copulatory sexual
      selection. Here we show that, on average, female eastern mosquitofish Gambusia
      holbrooki spent more time in association with males who received only a slight
      reduction in the length of the intromittent organ ('gonopodium') than males that
      received a greater reduction. This preference was, however, only expressed when
      females chose between two large males; for small males, there was no effect of
      genital size on female association time.

PMID- 19755530
TI  - Structural equation modelling reveals plant-community drivers of carbon storage
      in boreal forest ecosystems.
AB  - Boreal forest ecosystems are important drivers of the global carbon (C) cycle by
      acting as both sinks and sources of atmospheric CO(2). While several factors have
      been proposed as determining the ability of boreal forest to function as C sinks,
      little is known about their relative importance. In this study, we applied
      structural equation modelling to a previously published dataset involving 30
      boreal-forested islands that vary greatly in their historic fire regime, in order
      to explore the simultaneous influence of several factors believed to be important
      in influencing above-ground, below-ground and total ecosystem C accumulation. We
      found that wildfire was a major driver of ecosystem C sequestration, and exerted
      direct effects on below-ground C storage (presumably through humus combustion)
      and indirect effects on both above-ground and below-ground C storage through
      altering plant-community composition. By contrast, plant diversity influenced
      only below-ground C storage (and even then only weakly), while net primary
      productivity and decomposition had no detectable effect. Our results suggest that
      while boreal forests have great potential for storing significant amounts of C,
      traits of dominant plant species that promote below-ground C accumulation and the
      absence of wildfire are the most important drivers of C sequestration in these
      ecosystems.

PMID- 19755531
TI  - Linking killer whale survival and prey abundance: food limitation in the oceans'
      apex predator?
AB  - Killer whales (Orcinus orca) are large predators that occupy the top trophic
      position in the world's oceans and as such may have important roles in marine
      ecosystem dynamics. Although the possible top-down effects of killer whale
      predation on populations of their prey have received much recent attention,
      little is known of how the abundance of these predators may be limited by bottom
      up processes. Here we show, using 25 years of demographic data from two
      populations of fish-eating killer whales in the northeastern Pacific Ocean, that
      population trends are driven largely by changes in survival, and that survival
      rates are strongly correlated with the availability of their principal prey
      species, Chinook salmon (Oncorhynchus tshawytscha). Our results suggest that,
      although these killer whales may consume a variety of fish species, they are
      highly specialized and dependent on this single salmonid species to an extent
      that it is a limiting factor in their population dynamics. Other ecologically
      specialized killer whale populations may be similarly constrained to a narrow
      range of prey species by culturally inherited foraging strategies, and thus are
      limited in their ability to adapt rapidly to changing prey availability.

PMID- 19755532
TI  - Rowers' high: behavioural synchrony is correlated with elevated pain thresholds.
AB  - Physical exercise is known to stimulate the release of endorphins, creating a
      mild sense of euphoria that has rewarding properties. Using pain tolerance (a
      conventional non-invasive assay for endorphin release), we show that synchronized
      training in a college rowing crew creates a heightened endorphin surge compared
      with a similar training regime carried out alone. This heightened effect from
      synchronized activity may explain the sense of euphoria experienced during other
      social activities (such as laughter, music-making and dancing) that are involved
      in social bonding in humans and possibly other vertebrates.

PMID- 19755533
TI  - Invasive ants disrupt frugivory by endemic island birds.
AB  - Biological invasions can alter direct and indirect interactions between species,
      generating far-reaching changes in ecological networks that affect key ecological
      functions. We used model and real fruit assays to show that the invasion and
      formation of high-density supercolonies by the yellow crazy ant (YCA),
      Anoplolepis gracilipes, disrupt frugivory by endemic birds on Christmas Island,
      Indian Ocean. The overall handling rates of model fruits by birds were 2.2-2.4
      fold lower in ant-invaded than in uninvaded rainforest, and pecking rates by two
      bird species declined by 2.6- and 4.5-fold, respectively. YCAs directly
      interfered with frugivory; their experimental exclusion from fruiting displays
      increased fruit handling threefold to sixfold, compounding indirect effects of
      ant invasion on resources and habitat structure that influence bird abundances
      and behaviours. This invasive ant, whose high densities are sustained through
      mutualism with introduced scale insects, rapidly decreases fruit handling by
      endemic island birds and may erode a key ecological function, seed dispersal.
      Because most other invasive ant species form expansive, high-density
      supercolonies that depend in part on association with hemipteran mutualists, the
      effects that we report here on avian frugivore-plant associations may emerge
      across their introduced ranges.

PMID- 19755534
TI  - Development and dysmorphism in Joubert syndrome--short case series from India.
AB  - Five children with Joubert syndrome (JS), who fulfilled the criteria and had
      molar tooth sign (MTS) on magnetic resonance imaging were included in the study.
      Prominent forehead, open mouth and low set ears were consistent facial features.
      Severe developmental delay was seen in three children (66%). A differential
      developmental delay was noticed in all children and was independent of the
      radiological features. The children who had complications in the neonatal period
      were found to have more developmental delay on follow-up. The optimal control of
      sleep disturbances and hyperkinesis in one child resulted in a better cognitive
      performance. A regular neuro-developmental follow-up and interventions can
      optimize the potential of children with JS. In addition to the regular screening
      for retinal, renal and hepatic functions in JS, there is a need to monitor
      cognitive functions, sleep and behavior.

PMID- 19755535
TI  - The accuracy of national body fat cutoff levels in the prediction of elevated
      blood pressure among Brazilian male adolescents.
AB  - OBJECTIVE: To assess viability of the development of percentage body fat cutoffs
      based on blood pressure values in Brazilian adolescents. METHODS: A cross
      sectional study was conducted with a sample of 358 male subjects from 8 to 18
      years old. Blood pressure was measured by the oscilometric method, and body
      composition was measured by dual-energy X-ray absorptiometry (DXA). RESULTS: For
      the identification of elevated blood pressure, these nationally developed body
      fat cutoffs presented relative accuracy. The cutoffs were significantly
      associated with elevated blood pressure [odds ratio = 5.91 (95% confidence
      interval: 3.54-9.86)]. CONCLUSIONS: Development of national body fat cutoffs is
      viable, because presence of high accuracy is an indication of elevated blood
      pressure.

PMID- 19755536
TI  - Phosphate (Pi) starvation effect on the cytosolic Pi concentration and Pi
      exchanges across the tonoplast in plant cells: an in vivo 31P-nuclear magnetic
      resonance study using methylphosphonate as a Pi analog.
AB  - In vivo (31)P-NMR analyses showed that the phosphate (Pi) concentration in the
      cytosol of sycamore (Acer pseudoplatanus) and Arabidopsis (Arabidopsis thaliana)
      cells was much lower than the cytoplasmic Pi concentrations usually considered
      (60-80 mum instead of >1 mm) and that it dropped very rapidly following the onset
      of Pi starvation. The Pi efflux from the vacuole was insufficient to compensate
      for the absence of external Pi supply, suggesting that the drop of cytosolic Pi
      might be the first endogenous signal triggering the Pi starvation rescue
      metabolism. Successive short sequences of Pi supply and deprivation showed that
      added Pi transiently accumulated in the cytosol, then in the stroma and matrix of
      organelles bounded by two membranes (plastids and mitochondria, respectively),
      and subsequently in the vacuole. The Pi analog methylphosphonate (MeP) was used
      to analyze Pi exchanges across the tonoplast. MeP incorporated into cells via the
      Pi carrier of the plasma membrane; it accumulated massively in the cytosol and
      prevented Pi efflux from the vacuole. This blocking of vacuolar Pi efflux was
      confirmed by in vitro assays with purified vacuoles. Subsequent incorporation of
      Pi into the cells triggered a massive transfer of MeP from the cytosol to the
      vacuole. Mechanisms for Pi exchanges across the tonoplast are discussed in the
      light of the low cytosolic Pi level, the cell response to Pi starvation, and the
      Pi/MeP interactive effects.

PMID- 19755537
TI  - A single amino acid change in the enhancer of zeste ortholog CURLY LEAF results
      in vernalization-independent, rapid flowering in Arabidopsis.
AB  - Many strains of Arabidopsis (Arabidopsis thaliana) require exposure to prolonged
      cold for rapid flowering, a process known as vernalization. Vernalization in
      Arabidopsis results in the suppression of FLOWERING LOCUS C (FLC), a repressor of
      flowering. In a screen for mutants that no longer require vernalization for rapid
      flowering, we identified a dominant allele of the Enhancer of Zeste E(z) ortholog
      CURLY LEAF (CLF), clf-59. CLF is a Polycomb Group gene, and the clf-59 mutant
      protein contains a proline-to-serine transition in a cysteine-rich region that
      precedes the SET domain. Mutant plants are early flowering and have reduced FLC
      expression, but, unlike clf loss-of-function mutants, clf-59 mutants do not
      display additional pleiotropic phenotypes. clf-59 mutants have elevated levels of
      trimethylation on lysine 27 of histone H3 (H3K27me3) at FLC. Thus, clf-59 appears
      to be a gain-of-function allele, and this allele represses FLC without some of
      the components required for vernalization-mediated repression. In the course of
      this work, we also identified a marked difference in H3K27me3 levels at FLC
      between plants that contain and those that lack the FRIGIDA (FRI) gene.
      Furthermore, FRI appears to affect CLF occupancy at FLC; thus, our work provides
      insight into the molecular role that FRI plays in delaying the onset of
      flowering.

PMID- 19755538
TI  - Venturing beyond beans and peas: what can we learn from Chamaecrista?

PMID- 19755539
TI  - Biochemical characterization of AtRECQ3 reveals significant differences relative
      to other RecQ helicases.
AB  - Members of the conserved RecQ helicase family are important for the preservation
      of genomic stability. Multiple RecQ homologs within one organism raise the
      question of functional specialization. Whereas five different homologs are
      present in humans, the model plant Arabidopsis (Arabidopsis thaliana) carries
      seven RecQ homologs in its genome. We performed biochemical analysis of AtRECQ3,
      expanded upon a previous analysis of AtRECQ2, and compared their properties. Both
      proteins differ in their domain composition. Our analysis demonstrates that they
      are 3' to 5' helicases with similar activities on partial duplex DNA. However,
      they promote different outcomes with synthetic DNA structures that mimic Holliday
      junctions or a replication fork. AtRECQ2 catalyzes Holliday junction branch
      migration and replication fork regression, while AtRECQ3 cannot act on intact
      Holliday junctions. The observed reaction of AtRECQ3 on the replication fork is
      in line with unwinding the lagging strand. On nicked Holliday junctions, which
      have not been intensively studied with RecQ helicases before, AtRECQ3, but not
      AtRECQ2, shows a clear preference for one unwinding mechanism. In addition,
      AtRECQ3 is much more efficient at catalyzing DNA strand annealing. Thus, AtRECQ2
      and AtRECQ3 are likely to perform different tasks in the cell, and AtRECQ3
      differs in its biochemical properties from all other eukaryotic RECQ helicases
      characterized so far.

PMID- 19755540
TI  - Analysis of metabolic flux phenotypes for two Arabidopsis mutants with severe
      impairment in seed storage lipid synthesis.
AB  - Major storage reserves of Arabidopsis (Arabidopsis thaliana) seeds are
      triacylglycerols (seed oils) and proteins. Seed oil content is severely reduced
      for the regulatory mutant wrinkled1 (wri1-1; At3g54320) and for a double mutant
      in two isoforms of plastidic pyruvate kinase (pkpbeta(1)pkpalpha; At5g52920 and
      At3g22960). Both already biochemically well-characterized mutants were now
      studied by (13)C metabolic flux analysis of cultured developing embryos based on
      comparison with their respective genetic wild-type backgrounds. For both
      mutations, in seeds as well as in cultured embryos, the oil fraction was strongly
      reduced while the fractions of proteins and free metabolites increased. Flux
      analysis in cultured embryos revealed changes in nutrient uptakes and fluxes into
      biomass as well as an increase in tricarboxylic acid cycle activity for both
      mutations. While in both wild types plastidic pyruvate kinase (PK(p)) provides
      most of the pyruvate for plastidic fatty acid synthesis, the flux through PK(p)
      is reduced in pkpbeta(1)pkpalpha by 43% of the wild-type value. In wri1-1, PK(p)
      flux is even more reduced (by 82%), although the genes PKpbeta(1) and PKpalpha
      are still expressed. Along a common paradigm of metabolic control theory, it is
      hypothesized that a large reduction in PK(p) enzyme activity in
      pkpbeta(1)pkpalpha has less effect on PK(p) flux than multiple smaller reductions
      in glycolytic enzymes in wri1-1. In addition, only in the wri1-1 mutant is the
      large reduction in PK(p) flux compensated in part by an increased import of
      cytosolic pyruvate and by plastidic malic enzyme. No such limited compensatory
      bypass could be observed in pkpbeta(1)pkpalpha.

PMID- 19755541
TI  - Will elevated carbon dioxide concentration amplify the benefits of nitrogen
      fixation in legumes?

PMID- 19755542
TI  - Large-scale analysis of putative soybean regulatory gene expression identifies a
      Myb gene involved in soybean nodule development.
AB  - Nodulation is the result of a symbiosis between legumes and rhizobial bacteria in
      soil. This symbiosis is mutually beneficial, with the bacteria providing a source
      of nitrogen to the host while the plant supplies carbon to the symbiont. Nodule
      development is a complex process that is tightly regulated in the host plant cell
      through networks of gene expression. In order to examine this regulation in
      detail, a library of quantitative reverse transcription-polymerase chain reaction
      primer sets was developed for a large number of soybean (Glycine max) putative
      regulatory genes available in the current expressed sequence tag collection. This
      library contained primers specific to soybean transcription factor genes as well
      as genes involved in chromatin modification and translational regulation. Using
      this library, we analyzed the expression of this gene set during nodule
      development. A large number of genes were found to be differentially expressed,
      especially at the later stages of nodule development when active nitrogen
      fixation was occurring. Expression of these putative regulatory genes was also
      analyzed in response to the addition of nitrate as a nitrogen source. This
      comparative analysis identified genes that may be specifically involved in
      nitrogen assimilation, metabolism, and the maintenance of active nodules. To
      address this possibility, the expression of one such candidate was studied in
      more detail by expressing in soybean roots promoter beta-glucuronidase and green
      fluorescent protein fusions. This gene, named Control of Nodule Development
      (CND), encoded a Myb transcription factor gene. When the CND gene was silenced,
      nodulation was reduced. These results, associated with a strong expression of the
      CND gene in the vascular tissues, suggest a role for CND in controlling soybean
      nodulation.

PMID- 19755543
TI  - Global changes in the transcript and metabolic profiles during symbiotic nitrogen
      fixation in phosphorus-stressed common bean plants.
AB  - Phosphorus (P) deficiency is widespread in regions where the common bean
      (Phaseolus vulgaris), the most important legume for human consumption, is
      produced, and it is perhaps the factor that most limits nitrogen fixation. Global
      gene expression and metabolome approaches were used to investigate the responses
      of nodules from common bean plants inoculated with Rhizobium tropici CIAT899
      grown under P-deficient and P-sufficient conditions. P-deficient inoculated
      plants showed drastic reduction in nodulation and nitrogenase activity as
      determined by acetylene reduction assay. Nodule transcript profiling was
      performed through hybridization of nylon filter arrays spotted with cDNAs,
      approximately 4,000 unigene set, from the nodule and P-deficient root library. A
      total of 459 genes, representing different biological processes according to
      updated annotation using the UniProt Knowledgebase database, showed significant
      differential expression in response to P: 59% of these were induced in P
      deficient nodules. The expression platform for transcription factor genes based
      in quantitative reverse transcriptase-polymerase chain reaction revealed that 37
      transcription factor genes were differentially expressed in P-deficient nodules
      and only one gene was repressed. Data from nontargeted metabolic profiles
      indicated that amino acids and other nitrogen metabolites were decreased, while
      organic and polyhydroxy acids were accumulated, in P-deficient nodules.
      Bioinformatics analyses using MapMan and PathExpress software tools, customized
      to common bean, were utilized for the analysis of global changes in gene
      expression that affected overall metabolism. Glycolysis and glycerolipid
      metabolism, and starch and Suc metabolism, were identified among the pathways
      significantly induced or repressed in P-deficient nodules, respectively.

PMID- 19755544
TI  - A genome-scale metabolic model of Arabidopsis and some of its properties.
AB  - We describe the construction and analysis of a genome-scale metabolic model of
      Arabidopsis (Arabidopsis thaliana) primarily derived from the annotations in the
      Aracyc database. We used techniques based on linear programming to demonstrate
      the following: (1) that the model is capable of producing biomass components
      (amino acids, nucleotides, lipid, starch, and cellulose) in the proportions
      observed experimentally in a heterotrophic suspension culture; (2) that
      approximately only 15% of the available reactions are needed for this purpose and
      that the size of this network is comparable to estimates of minimal network size
      for other organisms; (3) that reactions may be grouped according to the changes
      in flux resulting from a hypothetical stimulus (in this case demand for ATP) and
      that this allows the identification of potential metabolic modules; and (4) that
      total ATP demand for growth and maintenance can be inferred and that this is
      consistent with previous estimates in prokaryotes and yeast.

PMID- 19755545
TI  - Recommendations for the administration of influenza vaccine in children allergic
      to egg.

PMID- 19755546
TI  - Campaigns to reduce antibiotic use in the US cannot compete with drug
      advertising, study says.

PMID- 19755551
TI  - Radial extracorporeal shockwave treatment compared with supervised exercises in
      patients with subacromial pain syndrome: single blind randomised study.
AB  - OBJECTIVE: To compare the effectiveness of radial extracorporeal shockwave
      treatment with that of supervised exercises in patients with shoulder pain.
      DESIGN: Single blind randomised study. SETTING: Outpatient clinic of physical
      medicine and rehabilitation department in Oslo, Norway. PARTICIPANTS: 104
      patients with subacromial shoulder pain lasting at least three months.
      INTERVENTIONS: Radial extracorporeal shockwave treatment: one session weekly for
      four to six weeks. Supervised exercises: two 45 minute sessions weekly for up to
      12 weeks. Primary outcome measure Shoulder pain and disability index. RESULTS: A
      treatment effect in favour of supervised exercises at 6, 12, and 18 weeks was
      found. The adjusted treatment effect was -8.4 (95% confidence interval -16.5 to 
      0.6) points. A significantly higher proportion of patients in the group treated
      with supervised exercises improved-odds ratio 3.2 (1.3 to 7.8). More patients in
      the shockwave treatment group had additional treatment between 12 and 18 weeks
      odds ratio 5.5 (1.3 to 26.4). CONCLUSION: Supervised exercises were more
      effective than radial extracorporeal shockwave treatment for short term
      improvement in patients with subacromial shoulder pain. TRIAL REGISTRATION:
      Clinical trials NCT00653081.

PMID- 19755552
TI  - Health and climate change.

PMID- 19755553
TI  - Politicians must heed health effects of climate change.

PMID- 19755556
TI  - Putting safety on the curriculum.

PMID- 19755561
TI  - Outbreak of E coli O157 is linked to Surrey open farm.

PMID- 19755563
TI  - Repertoire and evolution of miRNA genes in four divergent nematode species.
AB  - miRNAs are approximately 22-nt RNA molecules that play important roles in post
      transcriptional regulation. We have performed small RNA sequencing in the
      nematodes Caenorhabditis elegans, C. briggsae, C. remanei, and Pristionchus
      pacificus, which have diverged up to 400 million years ago, to establish the
      repertoire and evolutionary dynamics of miRNAs in these species. In addition to
      previously known miRNA genes from C. elegans and C. briggsae we demonstrate
      expression of many of their homologs in C. remanei and P. pacificus, and
      identified in total more than 100 novel expressed miRNA genes, the majority of
      which belong to P. pacificus. Interestingly, more than half of all identified
      miRNA genes are conserved at the seed level in all four nematode species, whereas
      only a few miRNAs appear to be species specific. In our compendium of miRNAs we
      observed evidence for known mechanisms of miRNA evolution including antisense
      transcription and arm switching, as well as miRNA family expansion through gene
      duplication. In addition, we identified a novel mode of miRNA evolution, termed
      "hairpin shifting," in which an alternative hairpin is formed with up- or
      downstream sequences, leading to shifting of the hairpin and creation of novel
      miRNA* species. Finally, we identified 21U-RNAs in all four nematodes, including
      P. pacificus, where the upstream 21U-RNA motif is more diverged. The
      identification and systematic analysis of small RNA repertoire in four nematode
      species described here provides a valuable resource for understanding the
      evolutionary dynamics of miRNA-mediated gene regulation.

PMID- 19755565
TI  - Theoretical frameworks and concept development.

PMID- 19755566
TI  - Does a view of nature promote relief from acute pain?
AB  - Inadequate control of acute pain is a well-recognized and serious problem.
      Distraction is one of the methods used in adjunct with medications to relieve
      pain. Nature-related sensory stimuli are frequently used for both distraction and
      relaxation. The human response model that focuses on individual adaptation to
      health conditions is used in this article to guide an analysis of relevant
      studies. Four studies in clinical settings evaluated the effect of nature (as a
      visual stimulus) to determine whether it promoted relief of acute pain. All these
      studies also used audio stimuli (nature sounds or music). Distracting visual and
      auditory stimuli used together provided stronger evidence of pain reduction than
      when either type of stimulus was used alone.

PMID- 19755568
TI  - Knowledge of motivational interviewing.
AB  - PURPOSE: The overall goal of this pilot study was to determine the effects of a
      motivational interviewing (MI) educational program on MI knowledge. DESIGN:
      Pretest/posttest intervention study. METHOD: Eleven participants completed a 20
      item test prior to a 6-hour course on motivational interviewing. Six of those
      participants completed a second 2-hour educational session and a posttest.
      FINDINGS: On average, participants increased their score from the pretest (mean
      [M] = 12.7, range 8-16; standard error [SE] = 1.256) to the posttest (M = 15.5,
      range 14-17; SE = 0.428). Although, this difference was not significant, t(5) = 
      2.49; p = .055; r = .55, given a standard level of significance of .5, the effect
      size was large, representing a substantive change. CONCLUSIONS: The motivational
      interviewing intervention was deemed clinically successful by the
      multidisciplinary committee based on the large effect size.

PMID- 19755569
TI  - A mutation in amino acid permease AAP6 reduces the amino acid content of the
      Arabidopsis sieve elements but leaves aphid herbivores unaffected.
AB  - The aim of this study was to investigate the role of the amino acid permease gene
      AAP6 in regulating phloem amino acid composition and then to determine the
      effects of this altered diet on aphid performance. A genotype of Arabidopsis
      thaliana (L.) was produced in which the function of the amino acid permease gene
      AAP6 (At5g49630) was abolished. Plants homozygous for the insertionally
      inactivated AAP6 gene had a significantly larger mean rosette width than the wild
      type and a greater number of cauline leaves. Seeds from the aap6 mutant were also
      significantly larger than those from the wild-type plants. Sieve element (SE) sap
      was collected by aphid stylectomy and the amino acids derivatized, separated, and
      quantified using Capillary Electrophoresis with Laser Induced Fluorescence (CE
      LIF). In spite of the large variation across samples, the total amino acid
      concentration of SE sap of the aap6 mutant plants was significantly lower than
      that of the wild-type plants. The concentrations of lysine, phenylalanine,
      leucine, and aspartic acid were all significantly lower in concentration in the
      aap6 mutant plants compared with wild-type plants. This is the first direct
      demonstration of a physiological role for an amino acid transporter in regulating
      SE composition in vivo. The amino acid availability in sieve element sap is
      thought to be the major limiting factor for aphid growth and reproduction.
      Despite the changes in their diet, the aphid Myzus persicae (Sulzer) displayed
      only small changes in feeding behaviour on mutant plants when measured using the
      Electronic Penetration Graph (EPG) technique. Salivation by the aphid into the SE
      (E1 phase) was increased on mutant plants but there was no significant effect on
      other feeding EPG behaviours, or in the rate of honeydew production. Consistent
      with the small effect on aphid feeding behaviour, there was only a small effect
      of reduced sieve element amino acid concentration on aphid reproduction. The data
      are discussed in relation to the regulation of phloem composition and the role of
      phloem amino acids in regulating aphid performance.

PMID- 19755570
TI  - Utricularia carnivory revisited: plants supply photosynthetic carbon to traps.
AB  - The rootless, aquatic Utricularia species belong to the largest and most
      cosmopolitan carnivorous plant genus. Populations of Utricularia plants are an
      important component of many standing, nutrient-poor, and humic waters. Carbon (C)
      allocation is an aspect of Utricularia's ecophysiology that has not been studied
      previously and there is considerable uncertainty about the functional and
      ecological benefit of the trap-associated microbial community and the potential
      role played by C exudation in enhancing plant-microbe interactions. A 13C
      labelling experiment was conducted in greenhouse conditions to determine the C
      allocation between plant tissues of increasing age and trap fluid in two
      Utricularia species. Both species allocated a majority of the newly fixed C into
      the fast growing shoot apex (46.1+/-8.6% in U. vulgaris and 56.1% in U.
      australis). Carbon allocation rapidly decreased with increasing age of the shoot,
      constituting only 8.0+/-4.0% and 6.7% of the total newly fixed C in the oldest
      analysed segments in U. vulgaris and U. australis, respectively. In the trap
      bearing shoot segments, the ratio of C exuded into the trap fluid to that in
      plant tissues increased markedly with age--in the oldest analysed segments twice
      as much newly fixed C was allocated into the trap fluid than the plant tissue.
      Overall, a significant amount of the newly fixed C, approximately 25% (U.
      vulgaris) and 20% (U. australis), was allocated to the trap fluid. The importance
      of C exudation for the development of the microbial community associated with the
      traps as well as for the growth and ecology of aquatic Utricularia is discussed.

PMID- 19755571
TI  - Symbolism of plants: examples from European-Mediterranean culture presented with
      biology and history of art: EPILOGUE.

PMID- 19755572
TI  - Effect of acute antidepressant administration on negative affective bias in
      depressed patients.
AB  - OBJECTIVE: Acute administration of an antidepressant increases positive affective
      processing in healthy volunteers, an effect that may be relevant to the
      therapeutic actions of these medications. The authors investigated whether this
      effect is apparent in depressed patients early in treatment, prior to changes in
      mood and symptoms. METHOD: In a double-blind, placebo-controlled, between-groups
      randomized design, the authors examined the effect of a single 4-mg dose of the
      norepinephrine reuptake inhibitor reboxetine on emotional processing. Thirty
      three depressed patients were recruited through primary care clinics and the
      community and matched to 31 healthy comparison subjects. Three hours after
      dosing, participants were given a battery of emotional processing tasks
      comprising facial expression recognition, emotional categorization, and memory.
      Ratings of mood, anxiety, and side effects were also obtained before and after
      treatment. RESULTS: Depressed patients who received placebo showed reduced
      recognition of positive facial expressions, decreased speed in responding to
      positive self-relevant personality adjectives, and reduced memory for this
      positive information compared to healthy volunteers receiving placebo. However,
      this effect was reversed in patients who received a single dose of reboxetine,
      despite the absence of changes in subjective ratings of mood or anxiety.
      CONCLUSIONS: Antidepressant drug administration modulates emotional processing in
      depressed patients very early in treatment, before changes occur in mood and
      symptoms. This effect may ameliorate the negative biases in information
      processing that characterize mood and anxiety disorders. It also suggests a
      mechanism of action compatible with cognitive theories of depression.

PMID- 19755573
TI  - Effects of chronic stress on memory decline in cognitively normal and mildly
      impaired older adults.
AB  - OBJECTIVE: The literature provides evidence of a strong relationship between
      greater stress and memory loss, but few studies have examined this relationship
      with both variables measured over time. The authors sought to determine the
      prospective association between subjective and objective measures of chronic
      stress and rate of memory decline in cognitively normal and mildly impaired older
      adults. METHOD: This longitudinal study was conducted at a university research
      center and included 61 cognitively normal subjects and 41 subjects with mild
      cognitive impairment (ages 65-97). Fifty-two subjects were followed for up to 3
      years (mean=2 years) and received repeated stress and cognitive assessments.
      Exclusion criteria were dementia, significant medical or psychiatric conditions,
      and medication use (e.g., corticosteroids) that might affect cortisol level or
      cognitive functioning. The main outcome measure was a regression-based slope
      reflecting performance change on tests of global cognition and episodic memory as
      a function of baseline diagnosis, recent life events, and salivary cortisol.
      Examiners were blind to stress ratings and cortisol levels at the time of
      cognitive testing. RESULTS: Higher event-based stress ratings collected over the
      follow-up period were associated with faster cognitive decline in subjects with
      mild cognitive impairment but not in cognitively normal subjects. In contrast,
      higher cortisol levels were associated with slower cognitive decline in subjects
      with mild cognitive impairment but not in cognitively normal subjects.
      CONCLUSIONS: Chronic stress affects cognitive functioning differently in
      cognitively normal subjects and those with mild cognitive impairment. Cortisol,
      while likely to have neurotoxic effects over time, may enhance cognitive
      functioning in older adults compromised by existing cognitive deficits.

PMID- 19755574
TI  - A randomized trial of dialectical behavior therapy versus general psychiatric
      management for borderline personality disorder.
AB  - OBJECTIVE: The authors sought to evaluate the clinical efficacy of dialectical
      behavior therapy compared with general psychiatric management, including a
      combination of psychodynamically informed therapy and symptom-targeted medication
      management derived from specific recommendations in APA guidelines for borderline
      personality disorder. METHOD: This was a single-blind trial in which 180 patients
      diagnosed with borderline personality disorder who had at least two suicidal or
      nonsuicidal self-injurious episodes in the past 5 years were randomly assigned to
      receive 1 year of dialectical behavior therapy or general psychiatric management.
      The primary outcome measures, assessed at baseline and every 4 months over the
      treatment period, were frequency and severity of suicidal and nonsuicidal self
      harm episodes. RESULTS: Both groups showed improvement on the majority of
      clinical outcome measures after 1 year of treatment, including significant
      reductions in the frequency and severity of suicidal and nonsuicidal self
      injurious episodes and significant improvements in most secondary clinical
      outcomes. Both groups had a reduction in general health care utilization,
      including emergency visits and psychiatric hospital days, as well as significant
      improvements in borderline personality disorder symptoms, symptom distress,
      depression, anger, and interpersonal functioning. No significant differences
      across any outcomes were found between groups. CONCLUSIONS: These results suggest
      that individuals with borderline personality disorder benefited equally from
      dialectical behavior therapy and a well-specified treatment delivered by
      psychiatrists with expertise in the treatment of borderline personality disorder.

PMID- 19755575
TI  - An FMRI study of the effects of psychostimulants on default-mode processing
      during Stroop task performance in youths with ADHD.
AB  - OBJECTIVE: The authors examined the effect of psychostimulants on brain activity
      in children and adolescents with ADHD performing the Stroop Color and Word Test.
      METHOD: The authors acquired 52 functional MRI scans in 16 youths with ADHD who
      were known responders to stimulant medication and 20 healthy comparison youths.
      Participants with ADHD were scanned on and off medication in a counterbalanced
      design, and comparison subjects were scanned once without medication. RESULTS:
      Stimulant medication significantly improved suppression of default-mode activity
      in the ventral anterior cingulate cortex in the ADHD group. When off medication,
      youths with ADHD were unable to suppress default-mode activity to the same degree
      as comparison subjects, whereas when on medication, they suppressed this activity
      to comparison group levels. Greater activation of the lateral prefrontal cortex
      when off medication predicted a greater reduction in ADHD symptoms when on
      medication. Granger causality analyses demonstrated that activity in the lateral
      prefrontal and ventral anterior cingulate cortices mutually influenced one
      another but that the influence of the ventral anterior cingulate cortex on the
      lateral prefrontal cortex was significantly reduced in youths with ADHD off
      medication relative to comparison subjects and increased significantly to normal
      levels when ADHD youths were on medication. CONCLUSIONS: Psychostimulants in
      youths with ADHD improved suppression of default-mode activity in the ventral
      anterior cingulate and posterior cingulate cortices, components of a circuit in
      which activity has been shown to correlate with the degree of mind-wandering
      during attentional tasks. Stimulants seem to improve symptoms in youths with ADHD
      by normalizing activity within this circuit and improving its functional
      interactions with the lateral prefrontal cortex.

PMID- 19755576
TI  - A developmental twin study of church attendance and alcohol and nicotine
      consumption: a model for analyzing the changing impact of genes and environment.
AB  - OBJECTIVE: Church attendance is one of the most consistent predictors of alcohol
      and nicotine consumption. The authors sought to clarify changes in the role of
      genetic and environmental factors in influencing church attendance and the
      interrelationship between church attendance and alcohol and nicotine use from
      early adolescence into adulthood. METHOD: The authors used data from two
      interview waves 6 years apart of 1,796 male twins from a population-based
      register, in which respondents were asked about current and past church
      attendance and psychoactive drug use. Structural twin models were fitted and
      tested using the Mx software program. RESULTS: As twins developed from childhood
      through adulthood, the influence of shared environmental factors on church
      attendance declined dramatically while genetic factors increased. In early and
      late adolescence, the negative correlations between church attendance and alcohol
      and nicotine consumption resulted largely from shared environmental factors. In
      adulthood, the inverse relationship between church attendance and substance use
      became stronger and arose largely from genetic factors. CONCLUSIONS: As
      individuals mature, they increasingly shape their own social environment in large
      part as a result of their genetically influenced temperament. When individuals
      are younger and living at home, frequent church attendance reflects a range of
      familial and social-environmental influences that reduce levels of substance use.
      In adulthood, by contrast, high levels of church attendance largely index
      genetically influenced temperamental factors that are protective against
      substance use. Using genetically informative designs such as twin studies, it is
      possible to show that the causes of the relationship between social risk factors
      and substance use can change dramatically over development.

PMID- 19755577
TI  - Familial aggregation of suicide explained by cluster B traits: a three-group
      family study of suicide controlling for major depressive disorder.
AB  - OBJECTIVE: There is substantial evidence suggesting that suicide aggregates in
      families. However, the extent of overlap between the liability to suicide and
      psychiatric disorders, particularly major depressive disorder, remains an
      important issue. Similarly, factors that account for the familial transmission of
      suicidal behavior remain unclear. Thus, through direct and blind assessment of
      first-degree relatives, the authors conducted a family study of suicide by
      examining three proband groups: probands who committed suicide in the context of
      major depressive disorder, living depressed probands with no history of suicidal
      behavior, and psychiatrically normal community comparison probands. METHOD:
      Participants were 718 first-degree relatives from 120 families: 296 relatives of
      51 depressed probands who committed suicide, 185 relatives of 34 nonsuicidal
      depressed probands, and 237 relatives of 35 community comparison subjects.
      Psychopathology, suicidal behavior, and behavioral measures were assessed via
      interviews. RESULTS: The relatives of probands who committed suicide had higher
      levels of suicidal behavior (10.8%) than the relatives of nonsuicidal depressed
      probands (6.5%) and community comparison probands (3.4%). Testing cluster B
      traits as intermediate phenotypes of suicide showed that the relatives of
      depressed probands who committed suicide had elevated levels of cluster B traits;
      familial predisposition to suicide was associated with increased levels of
      cluster B traits; cluster B traits demonstrated familial aggregation and were
      associated with suicide attempts among relatives; and cluster B traits mediated,
      at least in part, the relationship between familial predisposition and suicide
      attempts among relatives. Analyses were repeated for severity of attempts, where
      cluster B traits also met criteria for endophenotypes of suicide. CONCLUSIONS:
      Familial transmission of suicide and major depression, while partially
      overlapping, are distinct. Cluster B traits and impulsive-aggressive behavior
      represent intermediate phenotypes of suicide.

PMID- 19755581
TI  - Analysis of the Drosophila Clock promoter reveals heterogeneity in expression
      between subgroups of central oscillator cells and identifies a novel enhancer
      region.
AB  - The CLOCK-CYCLE (CLK-CYC) heterodimer lies at the heart of the circadian
      oscillator mechanism in Drosophila, yet little is known about the identity of
      transcription factors that regulate the expression of Clk and/or cyc. Here, the
      authors have used a transgenic approach to isolate regions of the Clk locus that
      are necessary for expression in central oscillator neurons in the adult fly
      brain. This analysis shows that central clock cells can be subdivided into 2
      distinct groups based on Clk gene regulation. Expression in the lateral neuron
      (LN), dorsal neuron 1 anterior (DN1a) and 2 (DN2) clusters requires cis-elements
      located in a 122 base-pair (bp) region (-206 to -84) of the Clk promoter.
      Expression in the remaining dorsal neurons, 1 posterior (DN1p) and 3 (DN3) and
      the lateral posterior neurons (LPN), requires regulatory elements located in the 
      856 to -206 region. In addition, expression in photoreceptors of the compound eye
      is enhanced by cis-elements located in a 3rd region of the Clk locus (-1982 to 
      856). This region also enhances expression in nonoscillator cells in the brain
      including the Kenyon cells, but expression in these neurons is suppressed by
      regulatory sites located further upstream of -1982. The authors' analysis reveals
      clear heterogeneity in Clk gene expression in the adult brain and provides a
      necessary focus to isolate novel transcription factors that bind at the Clk locus
      to regulate expression in different oscillator neuron subgroups. These results
      also suggest that the DN1a/DN2 neurons may have more molecular commonality with
      the LNs than they do with the DN1p/DN3/LPN neurons. Finally, this analysis has
      generated new transgenic lines that will enable genes to be misexpressed in
      subgroups of central oscillator cells that have previously been resistant to
      discrete genetic manipulation. Hence, these lines provide important new tools to
      facilitate a more complete dissection of the neural network that regulates output
      rhythms in physiology and behavior.

PMID- 19755580
TI  - Basis of robustness and resilience in the suprachiasmatic nucleus: individual
      neurons form nodes in circuits that cycle daily.
AB  - How the cellular elements of the SCN are synchronized to each other is not well
      understood. We explore circadian oscillations manifest at the level of the cell,
      the tissue, and the whole animal to better understand intra-SCN synchrony and
      master clock function of the nucleus. At each level of analysis, responses to
      variations in operating environment (robustness), and following damage to
      components of the system (resilience), provide insight into the mechanisms
      whereby the SCN orchestrates circadian timing. Tissue level rhythmicity reveals
      circuits associated with an orderly spatiotemporal daily pattern of activity that
      is not predictable from their cellular elements. Specifically, in stable state,
      some SCN regions express low amplitude or undetectable rhythms in clock gene
      expression while others produce high amplitude oscillations. Within the SCN,
      clock gene expression follows a spatially ordered, repeated pattern of activation
      and inactivation. This pattern of activation is plastic and subserves responses
      to changes in external and internal conditions. Just as daily rhythms at the
      cellular level depend on sequential expression and interaction of clock genes, so
      too do rhythms at the SCN tissue level depend on sequential activation of local
      nodes. We hypothesize that individual neurons are organized into nodes that are
      themselves sequentially activated across the volume of the SCN in a cycle that
      repeats on a daily basis. We further propose that robustness is expressed in the
      ability of the SCN to sustain rhythmicity over a wide range of internal and
      external conditions, and that this reflects plasticity of the underlying nodes
      and circuits. Resilience is expressed in the ability of SCN cells to oscillate
      and to sustain activity-related rhythms at the behavioral level. Importantly,
      other aspects of pacemaker function remain to be examined.

PMID- 19755578
TI  - Genome-wide linkage and follow-up association study of postpartum mood symptoms.
AB  - OBJECTIVE: Family studies have suggested that postpartum mood symptoms might have
      a partly genetic etiology. The authors used a genome-wide linkage analysis to
      search for chromosomal regions that harbor genetic variants conferring
      susceptibility for such symptoms. The authors then fine-mapped their best linkage
      regions, assessing single nucleotide polymorphisms (SNPs) for genetic association
      with postpartum symptoms. METHOD: Subjects were ascertained from two studies: the
      NIMH Genetics Initiative Bipolar Disorder project and the Genetics of Recurrent
      Early-Onset Depression. Subjects included women with a history of pregnancy, any
      mood disorder, and information about postpartum symptoms. In the linkage study,
      1,210 women met criteria (23% with postpartum symptoms), and 417 microsatellite
      markers were analyzed in multipoint allele sharing analyses. For the association
      study, 759 women met criteria (25% with postpartum symptoms), and 16,916 SNPs in
      the regions of the best linkage peaks were assessed for association with
      postpartum symptoms. RESULTS: The maximum linkage peak for postpartum symptoms
      occurred on chromosome 1q21.3-q32.1, with a chromosome-wide significant
      likelihood ratio Z score (Z(LR)) of 2.93 (permutation p=0.02). This was a
      significant increase over the baseline Z(LR) of 0.32 observed at this locus among
      all women with a mood disorder (permutation p=0.004). Suggestive linkage was also
      found on 9p24.3-p22.3 (Z(LR)=2.91). In the fine-mapping study, the strongest
      implicated gene was HMCN1 (nominal p=0.00017), containing four estrogen receptor
      binding sites, although this was not region-wide significant. CONCLUSIONS: This
      is the first study to examine the genetic etiology of postpartum mood symptoms
      using genome-wide data. The results suggest that genetic variations on
      chromosomes 1q21.3-q32.1 and 9p24.3-p22.3 may increase susceptibility to
      postpartum mood symptoms.

PMID- 19755582
TI  - Genetic analysis of ectopic circadian clock induction in Drosophila.
AB  - Cell-autonomous feedback loops underlie the molecular oscillations that define
      circadian clocks. In Drosophila the transcription factor Clk activates multiple
      clock components of feedback loops many of which feed back and regulate Clk
      expression or activity. Previously the authors evoked similar molecular
      oscillations in putatively naive neurons in Drosophila by ectopic expression of a
      single gene, Clk, suggesting a master regulator function. Using molecular
      oscillations of the core clock component PERIOD (PER), the authors observed
      dramatic and widespread molecular oscillations throughout the brain in flies
      expressing ectopic Clk. Consistent with the master regulator hypothesis, they
      found that Clk is uniquely capable of inducing ectopic clocks as ectopic
      induction of other clock components fails to induce circadian rhythms. Clk also
      induces oscillations even when expression is adult restricted, suggesting that
      ectopic clocks can even be induced in differentiated cells. However, if transgene
      expression is discontinued, PER expression disappears, indicating that Clk must
      be continually active to sustain ectopic clock function. In some cases Clk
      mediated PER induction was observed without apparent synchronous cycling, perhaps
      due to desynchronization of rhythms between clocks or truly cell autonomous
      arrhythmic PER expression, indicating that additional factors may be necessary
      for coherent rhythms in cells ectopically expressing Clk. To determine minimal
      requirements for circadian clock induction by Clk, the authors determined the
      genetic requirements of ectopic clocks. No ectopic clocks are induced in mutants
      of Clk's heterodimeric partner cyc. In addition, noncycling PER is observed when
      ectopic Clk is induced in a cryb mutant background. While other factors may
      contribute, these results indicate that persistent Clock induction is uniquely
      capable of broadly inducing ectopic rhythms even in adults, consistent with a
      special role at the top of a clock gene hierarchy.

PMID- 19755583
TI  - The clock gene period plays an essential role in photoperiodic control of nymphal
      development in the cricket Modicogryllus siamensis.
AB  - Photoperiodic regulation of development is a common strategy for insects in the
      temperate zone to adapt to the seasonally changing environment. Although the
      circadian clock is generally thought to be involved, the underlying time
      measurement mechanism is still elusive. Here, we demonstrate that the circadian
      clock gene period (per) plays an essential role in the photoperiodic regulation
      of nymphal development in the cricket Modicogryllus siamensis. Nymphal
      development of this cricket depends on photoperiods, being accelerated by long
      days and slowed down by short days. We examined the role of per in the nymphal
      photoperiodic response as well as circadian rhythm generation using parental RNA
      interference (pRNAi). per mRNA levels in nymphal heads showed a rhythmic
      expression with the pattern dependent on photoperiods, and pRNAi significantly
      suppressed the per mRNA level with no significant rhythmicity in the early
      nymphal stage. Irrespective of photoperiods, nymphs treated with per pRNAi showed
      adult emergence patterns neither of intact nymphs nor of DsRed2 pRNAi nymphs kept
      under long days or under short days but similar to those kept under constant dark
      conditions. Most per pRNAi adults showed arrhythmic or aberrant circadian
      locomotor activity. These results suggest that the photoperiodic time measurement
      requires the normal circadian clock that is controlled by the per gene.

PMID- 19755585
TI  - Twilight and photoperiod affect behavioral entrainment in the house mouse (Mus
      musculus).
AB  - The effect of twilight transitions on entrainment of C57BL/6JOlaHsd mice (Mus
      musculus) was studied using light-dark cycles of different photoperiods (6, 12,
      and 18 h) and twilight transitions of different durations (0, 1, and 2 h). Phase
      angle differences of the onset, center of gravity, and offset of activity,
      activity duration (alpha), as well as free-running period (tau) in continuous
      darkness were analyzed. The main finding was that for all conditions the onset of
      activity was close to dusk or lights-off except for the short photoperiod with 2
      h of twilight where activity onset was on average 5.3 (SEM 1.07) h after lights
      off. This finding contrasts with the results of Boulos and Macchi for Syrian
      hamsters where a 5.9-h earlier activity onset was observed when similar
      photoperiod and twilight conditions are compared with a rectangular LD cycle. The
      authors suggest the opposite effects of 2 h of twilight in the 2 species may be
      related to their different free-running periods under DD conditions following
      entrainment to short photoperiod with 2-h twilight conditions. Since the authors
      observed larger variation in phase angle of entrainment in longer twilight
      conditions, twilight does not necessarily form a stronger zeitgeber.

PMID- 19755584
TI  - Circadian modulation of melanopsin-driven light response in rat ganglion-cell
      photoreceptors.
AB  - Intrinsically photosensitive retinal ganglion cells (ipRGCs) project to the
      suprachiasmatic nucleus (SCN) and are essential for normal photic entrainment of
      global circadian rhythms in physiology and behavior. The effect of light on the
      central clock is dependent on circadian phase, and the retina itself contains
      intrinsic circadian oscillators that can alter its sensitivity to light. This
      raises the possibility that the ipRGCs, and hence the photoentraining signals in
      the retinohypothalamic tract, are subject to circadian modulation. Although the
      ipRGC photopigment melanopsin reportedly exhibits circadian variations in
      expression, there has been no direct test of the hypothesis that ipRGC
      sensitivity is under circadian control. Here, the authors provide such a test by
      measuring the sensitivity of intrinsic photoresponses of rat ipRGCs at 4
      circadian times (CTs) using multielectrode array recording. There was little if
      any circadian modulation in the threshold of intrinsic ipRGC photoresponses.
      However, very bright light evoked significantly more spiking early in the
      subjective night (CT12-13) than at other circadian phases. Thus, the gain of the
      melanopsin-driven response is slightly increased in the early night, at roughly
      the circadian phase when melanopsin synthesis is thought to be elevated. However,
      this gain change is probably too modest to contribute much to shape the phase
      response curve (PRC) for behavioral photoentrainment.

PMID- 19755586
TI  - Circannual phase response curves to short and long photoperiod in the European
      hamster.
AB  - This study investigated in male European hamsters (Cricetus cricetus ) whether
      entrainment of circannual rhythms follows the principles of the nonparametric
      entrainment model. In 2 experiments the times of the year when long (LP) or short
      photoperiod (SP) are able to synchronize the reproductive cycle were determined,
      by recording phase response curves (PRCs). A total of 28 groups of 10 hamsters
      were synchronized by SP, before being subjected to 2 converse experiments: a) 14
      groups were transferred to constant LP, only interrupted by SP for 1 month (SP
      pulse), the pulse being increasingly delayed between groups by 2 weeks or 1 month
      steps; and b) the remaining 14 groups stayed in constant SP interrupted by LP for
      1 month (LP-pulse) at different phases of the cycle. In a 3rd experiment 5 groups
      of 10 European hamsters were subjected to constant LP interrupted by 1-month SP
      pulses in regular non-365-day zeitgeber intervals (circannual T-cycles) differing
      between groups (c). The reproductive state was checked every 2 or 4 weeks. The
      PRCs revealed that an SP-pulse had a very strong phase-resetting capability of 
      180 degrees to at least +81 degrees in subjective summer (a). During subjective
      winter when the animals hibernate, a SP-pulse had only weak effectiveness (a)
      whereas an LP-pulse advanced the circannual clock by up to +41 degrees (b). In
      the latter conditions a further advance of up to +156 degrees was achieved by the
      decrease in photoperiod at the return to SP conditions, which terminated the
      reproductive phase already after 4 to 5 weeks. In different circannual T-cycles
      the animals entrained for at least 2 cycles (c). In conclusion, 1) the circannual
      rhythm of European hamsters can be entrained by one photoperiodic signal per
      cycle, 2) the decrease in photoperiod is most important for its synchronization,
      and 3) as in circadian clocks the resetting of circannual clocks follows the
      principles of the nonparametric entrainment model.

PMID- 19755587
TI  - Controlled patterns of daytime light exposure improve circadian adjustment in
      simulated night work.
AB  - Circadian misalignment between the endogenous circadian signal and the imposed
      rest-activity cycle is one of the main sources of sleep and health troubles in
      night shift workers. Timed bright light exposure during night work can reduce
      circadian misalignment in night workers, but this approach is limited by
      difficulties in incorporating bright light treatment into most workplaces.
      Controlled light and dark exposure during the daytime also has a significant
      impact on circadian phase and could be easier to implement in real-life
      situations. The authors previously described distinctive light exposure patterns
      in night nurses with and without circadian adaptation. In the present study, the
      main features of these patterns were used to design daytime light exposure
      profiles. Profiles were then tested in a laboratory simulation of night work to
      evaluate their efficacy in reducing circadian misalignment in night workers. The
      simulation included 2 day shifts followed by 4 consecutive night shifts (2400
      0800 h). Healthy subjects (15 men and 23 women; 20-35 years old) were divided
      into 3 groups to test 3 daytime light exposure profiles designed to produce
      respectively a phase delay (delay group, n=12), a phase advance (advance group,
      n=13), or an unchanged circadian phase (stable group, n=13). In all 3 groups,
      light intensity was set at 50 lux during the nights of simulated night work.
      Salivary dim light melatonin onset (DLMO) showed a significant phase advance of
      2.3 h (+/-1.3 h) in the advance group and a significant phase delay of 4.1 h (+/
      1.3 h) in the delay group. The stable group showed a smaller but significant
      phase delay of 1.7 h (+/-1.6 h). Urinary 6-sulfatoxymelatonin (aMT6s) acrophases
      were highly correlated to salivary DLMOs. Urinary aMT6s acrophases were used to
      track daily phase shifts. They showed that phase shifts occurred rapidly and
      differed between the 3 groups by the 3rd night of simulated night work. These
      results show that significant phase shifts can be achieved in night workers by
      controlling daytime light exposure, with no nighttime intervention.

PMID- 19755594
TI  - Medical image and data sharing: are we there yet?

PMID- 19755595
TI  - Imaging-based quantification of hepatic fat: methods and clinical applications.
AB  - Fatty liver disease comprises a spectrum of conditions (simple hepatic steatosis,
      steatohepatitis with inflammatory changes, and end-stage liver disease with
      fibrosis and cirrhosis). Hepatic steatosis is often associated with diabetes and
      obesity and may be secondary to alcohol and drug use, toxins, viral infections,
      and metabolic diseases. Detection and quantification of liver fat have many
      clinical applications, and early recognition is crucial to institute appropriate
      management and prevent progression. Histopathologic analysis is the reference
      standard to detect and quantify fat in the liver, but results are vulnerable to
      sampling error. Moreover, it can cause morbidity and complications and cannot be
      repeated often enough to monitor treatment response. Imaging can be repeated
      regularly and allows assessment of the entire liver, thus avoiding sampling
      error. Selection of appropriate imaging methods demands understanding of their
      advantages and limitations and the suitable clinical setting. Ultrasonography is
      effective for detecting moderate or severe fatty infiltration but is limited by
      lack of interobserver reliability and intraobserver reproducibility. Computed
      tomography allows quantitative and qualitative evaluation and is generally highly
      accurate and reliable; however, the results may be confounded by hepatic
      parenchymal changes due to cirrhosis or depositional diseases. Magnetic resonance
      (MR) imaging with appropriate sequences (eg, chemical shift techniques) has
      similarly high sensitivity, and MR spectroscopy provides unique advantages for
      some applications. However, both are expensive and too complex to be used to
      monitor steatosis.

PMID- 19755596
TI  - Volvulus of the gastrointestinal tract: appearances at multimodality imaging.
AB  - Volvulus of the gastrointestinal tract, a clinically relevant cause of acute or
      recurring abdominal pain in adults, remains a diagnostic dilemma for radiologists
      in a large number of cases. The clinical symptoms associated with volvulus are
      often nonspecific and include pain and nausea with vomiting. Yet referring
      clinicians often rely on radiologists to make the diagnosis; volvulus is rarely
      diagnosed clinically. Radiography, fluoroscopy, and computed tomography are the
      imaging methods most often used for this purpose. Prompt diagnosis is critical to
      avoid life-threatening complications such as bowel ischemia and infarction. Thus,
      it is useful for radiologists to be familiar with the various appearances of
      volvulus throughout the gastrointestinal tract.

PMID- 19755597
TI  - Characterization of genitourinary lesions with diffusion-weighted imaging.
AB  - Diffusion-weighted imaging has been widely accepted as a powerful imaging
      technique in neuroradiology. Until recently, the inclusion of diffusion-weighted
      sequences in body imaging protocols has been hindered by technical limitations.
      However, with advances in magnetic resonance (MR) imaging technology and
      technique, these limitations are being overcome. The addition of diffusion
      weighted sequences to routine abdominopelvic MR imaging protocols has been found
      to yield diagnostically useful information with only a minimal increase in
      imaging time. More specifically, the use of diffusion-weighted imaging in the
      genitourinary system can facilitate the detection and characterization of
      genitourinary tract lesions that demonstrate equivocal signal intensity
      characteristics with routine MR imaging sequences. Diffusion-weighted imaging is
      not only helpful in differentiating benign from malignant processes, but it can
      also be used to assess meta-static lesions, possible tumor recurrence, and
      treatment response. Because it does not require injection of a gadolinium-based
      contrast agent, diffusion-weighted imaging can be used in patients with renal
      insufficiency or contrast material allergy. Most of the body diffusion-weighted
      imaging studies reported in the literature to date have been conducted with 1.5-T
      magnets. However, the feasibility of body diffusion-weighted imaging at 3.0 T is
      currently under investigation in an effort to determine the efficacy of the
      routine inclusion of diffusion-weighted imaging sequences in 3.0-T body MR
      imaging protocols.

PMID- 19755598
TI  - Adrenal imaging with multidetector CT: evidence-based protocol optimization and
      interpretative practice.
AB  - Computed tomography (CT) is an integral tool in the assessment of adrenal masses.
      Dedicated adrenal CT is performed for a range of indications, including hormonal
      abnormalities suggestive of a functional adrenal mass and adrenal cancer staging.
      It is important to have an understanding of the published data that guide
      protocol design and image interpretation. Whether an adrenal mass is identified
      serendipitously or is being imaged for further characterization, there are
      several CT findings that contribute to the diagnosis, such as lesion size,
      precontrast attenuation, level of enhancement at 60 seconds and on delayed
      images, percentage washout on delayed images, histogram analysis, and extent
      (involvement of the inferior vena cava and bilaterality). In the past decade, a
      body of pertinent literature has evolved, addressing each of these measures
      individually.

PMID- 19755599
TI  - Adrenal mass imaging with multidetector CT: pathologic conditions, pearls, and
      pitfalls.
AB  - The adrenal gland is involved by a range of neoplasms, including primary and
      metastatic malignant tumors; however, the most common tumor detected is the
      incidental benign adenoma. Although computed tomographic (CT) findings will not
      always yield a definitive diagnosis, attention to these findings provides a road
      map to guide image interpretation. Adenomas typically demonstrate rapid washout,
      which is defined as an absolute percentage washout (APW) of more than 60% and a
      relative percentage washout (RPW) of more than 40% on delayed images.
      Adrenocortical carcinoma typically has an RPW of less than 40%; however, large
      size and heterogeneity are more reliable indicators of the diagnosis than are
      washout values. Washout characteristics of pheochromocytoma are variable; in
      conjunction with high levels of dynamic enhancement, pheochromocytomas may mimic
      adenoma (ie, APW > 60%, RPW > 40%). Myelolipomas appear as well-defined masses
      with variable quantities of fat and soft tissue. After contrast material
      administration, metastases usually demonstrate slower washout on delayed images
      (APW < 60%, RPW < 40%) than do adenomas, although hypervascular metastases may
      enhance similarly to pheochromocytoma. Finally, a number of nonadrenal pathologic
      conditions have been reported to mimic adrenal masses at CT.

PMID- 19755600
TI  - Female infertility: a systematic approach to radiologic imaging and diagnosis.
AB  - Imaging plays a key role in the diagnostic evaluation of women for infertility.
      The pelvic causes of female infertility are varied and range from tubal and
      peritubal abnormalities to uterine, cervical, and ovarian disorders. In most
      cases, the imaging work-up begins with hysterosalpingography to evaluate
      fallopian tube patency. Uterine filling defects and contour abnormalities may be
      discovered at hysterosalpingography but typically require further
      characterization with hysterographic or pelvic ultrasonography (US) or pelvic
      magnetic resonance (MR) imaging. Hysterographic US helps differentiate among
      uterine synechiae, endometrial polyps, and submucosal leiomyomas. Pelvic US and
      MR imaging help further differentiate among uterine leiomyomas, adenomyosis, and
      the various mullerian duct anomalies, with MR imaging being the most sensitive
      modality for detecting endometriosis. The presence of cervical disease may be
      inferred initially on the basis of difficulty or failure of cervical cannulation
      at hysterosalpingography. Ovarian abnormalities are usually detected at US. The
      appropriate selection of imaging modalities and accurate characterization of the
      various pelvic causes of infertility are essential because the imaging findings
      help direct subsequent patient care.

PMID- 19755601
TI  - Imaging of the placenta: a multimodality pictorial review.
AB  - The placenta is often overlooked in the routine evaluation of a normal gestation,
      receiving attention only when an abnormality is detected. Although uncommon,
      abnormalities of the placenta are important to recognize owing to the potential
      for maternal and fetal morbidity and mortality. Pathologic conditions of the
      placenta include placental causes of hemorrhage, gestational trophoblastic
      disease, retained products of conception, nontrophoblastic placental tumors,
      metastases, and cystic lesions. Sonography remains the imaging modality of choice
      for evaluation of the placenta. Magnetic resonance (MR) imaging can be of added
      diagnostic value when further characterization is required, particularly in the
      setting of invasive placental processes such as placenta accreta and gestational
      trophoblastic disease. Computed tomography (CT) has a limited role in the
      evaluation of placental disease owing to limited tissue characterization,
      compared with that of MR imaging, and the radiation risk to the fetus; this risk
      often outweighs the benefit. The primary role for CT is in the evaluation of
      trauma and gestational trophoblastic disease, for which it allows
      characterization of the primary lesion and distant metastases.

PMID- 19755602
TI  - CT angiography of the cardiac valves: normal, diseased, and postoperative
      appearances.
AB  - Although echocardiography remains the principal imaging technique for assessment
      of the cardiac valves, contrast material-enhanced electrocardiographically gated
      computed tomographic (CT) angiography is proving to be an increasingly valuable
      complementary modality in this setting. CT angiography allows excellent
      visualization of the morphologic features and function of the normal valves, as
      well as of a wide range of valve diseases, including congenital and acquired
      diseases, infectious endocarditis, and complications of valve replacement. The
      number, thickness, and opening and closing of the valve leaflets, as well as the
      presence of valve calcification, can be directly observed. CT angiography also
      permits simultaneous assessment of the valves and coronary arteries, which may
      prove valuable in presurgical planning. Unlike echocardiography and magnetic
      resonance imaging, however, CT angiography requires ionizing radiation and does
      not provide a direct measure of the valvular pressure gradient. Nevertheless,
      with further development of related imaging techniques, CT angiography can be
      expected to play an increasingly important role in the evaluation of the cardiac
      valves. Supplemental material available at
      http://radiographics.rsna.org/cgi/content/full/29/5/1393/DC1.

PMID- 19755603
TI  - High-resolution MR imaging of the cervical arterial wall: what the radiologist
      needs to know.
AB  - The emergence of high-resolution rapid imaging methods has enabled magnetic
      resonance (MR) imagers to noninvasively image the fine internal structure of
      cervical arterial walls. In this article, a comprehensive guide to performing
      high-resolution MR imaging of cervical arteries is provided, including the choice
      of coils, sequences, and imaging parameters, as well as tips for optimal image
      quality. Explanations and illustrations are given of using high-resolution MR
      imaging to quantify plaque volume, determine atherosclerotic plaque burden,
      depict plaque composition, and ultimately identify unstable plaque before it
      leads to a clinical event. Finally, the role of high-resolution MR imaging in the
      diagnosis of cervical dissection and inflammatory disease of the arterial wall is
      emphasized.

PMID- 19755604
TI  - Principles, techniques, and applications of T2*-based MR imaging and its special
      applications.
AB  - T2* relaxation refers to decay of transverse magnetization caused by a
      combination of spin-spin relaxation and magnetic field inhomogeneity. T2*
      relaxation is seen only with gradient-echo (GRE) imaging because transverse
      relaxation caused by magnetic field inhomogeneities is eliminated by the 180
      degrees pulse at spin-echo imaging. T2* relaxation is one of the main
      determinants of image contrast with GRE sequences and forms the basis for many
      magnetic resonance (MR) applications, such as susceptibility-weighted (SW)
      imaging, perfusion MR imaging, and functional MR imaging. GRE sequences can be
      made predominantly T2* weighted by using a low flip angle, long echo time, and
      long repetition time. GRE sequences with T2*-based contrast are used to depict
      hemorrhage, calcification, and iron deposition in various tissues and lesions. SW
      imaging uses phase information in addition to T2*-based contrast to exploit the
      magnetic susceptibility differences of the blood and of iron and calcification in
      various tissues. Perfusion MR imaging exploits the signal intensity decrease that
      occurs with the passage of a high concentration of gadopentetate dimeglumine
      through the microvasculature. Change in oxygen saturation during specific tasks
      changes the local T2*, which leads to the blood oxygen level-dependent effect
      seen at functional MR imaging. The basics of T2* relaxation, T2*-weighted
      sequences, and their clinical applications are presented, followed by the
      principles, techniques, and clinical uses of four T2*-based applications,
      including SW imaging, perfusion MR imaging, functional MR imaging, and iron
      overload imaging.

PMID- 19755605
TI  - MR imaging at 3.0 T in children: technical differences, safety issues, and
      initial experience.
AB  - The high signal-to-noise ratio and contrast-to-noise ratio of 3.0-T magnetic
      resonance (MR) imaging can be used to obtain high-resolution thin-section images
      in a short acquisition time. These advantages are associated with an increased
      specific absorption rate (SAR) and more artifacts owing to B(1) inhomogeneity and
      increased susceptibility and chemical shift. Potential advantages of 3-T imaging
      in children include acquisition of good-quality images even with a small field of
      view (FOV). The shorter overall acquisition time of 3-T imaging is useful in
      children, who may not be able to cooperate for long. Shorter acquisition times
      also improve safety by reducing patient monitoring time within the enclosed bore
      of an MR imaging unit. SAR-related issues and dielectric artifacts are less
      problematic with a small FOV. Parallel imaging helps reduce SAR, susceptibility
      artifacts, and blurring of T2-weighted fast spin-echo (FSE) and single-shot FSE
      images by reducing the echo train length.

PMID- 19755606
TI  - Pediatric FDG PET/CT: physiologic uptake, normal variants, and benign conditions.
AB  - Positron emission tomography (PET) with 2-[fluorine-18]fluoro-2-deoxy-D-glucose
      (FDG) is increasingly being used in the evaluation of pediatric oncology
      patients. However, the normal distribution of (18)F FDG uptake in children is
      unique and may differ from that in adults. A number of physiologic variants are
      commonly encountered, including normal physiologic uptake in the head and neck,
      heart, breast, thymus, liver, spleen, gastrointestinal tract, genital system,
      urinary collecting system, bone marrow, muscles, and brown adipose tissue. Benign
      lesions with increased (18)F FDG uptake are also frequently seen and can be
      misinterpreted as malignancies. In addition, the use of combined PET/computed
      tomographic (CT) scanners is associated with pitfalls and artifacts such as
      attenuation correction and misregistration. Proper interpretation of pediatric
      (18)F FDG PET/CT studies requires knowledge of the normal distribution of (18)F
      FDG uptake in children, as well as of the aforementioned physiologic variants,
      benign lesions, and PET/CT-related artifacts. Knowing these potential causes of
      misinterpretation can increase accuracy in PET image interpretation, decrease the
      number of unnecessary follow-up studies or procedures, and improve patient
      treatment.

PMID- 19755607
TI  - Pediatric FDG PET/CT: Physiologic uptake, normal variants, and benign conditions
      [corrected].
AB  - Ewing sarcoma family tumors account for approximately 3% of all pediatric
      cancers, making them the second most common bone malignancies in children and
      adolescents. Advances in the treatment of localized disease have dramatically
      prolonged the survival of patients in whom Ewing sarcoma is diagnosed, but the
      prognosis for patients with metastatic or recurrent disease remains poor.
      Radiologic evaluation of Ewing sarcoma can help (a) detect and accurately assess
      the extent of disease prior to treatment, (b) determine whether metastatic or
      recurrent disease is present, and (c) monitor therapy response. Standard imaging
      evaluation of bone and soft-tissue sarcomas typically consists of conventional
      radiography, magnetic resonance (MR) imaging, computed tomography (CT), and bone
      scintigraphy. Positron emission tomography (PET) with 2-[fluorine-18]fluoro-2
      deoxy-D-glucose (FDG) provides unique information with regard to the biologic
      activity of Ewing sarcomas. It represents a noninvasive means of estimating
      histologic tumor grade and can be used to detect progression or regression of
      disease prior to anatomic imaging. Such information can be used to optimize
      staging, restaging, and assessment of therapy response. Functional imaging with
      FDG PET can also potentially help predict patient prognosis both before and after
      neoadjuvant therapy. FDG PET does have inherent limitations that must be
      acknowledged to avoid potential diagnostic pitfalls and is optimally used in
      combination with correlative anatomic imaging modalities such as CT and MR
      imaging. Nevertheless, FDG PET provides unique physiologic information that often
      has important clinical implications.

PMID- 19755608
TI  - Pigmented lesions of the central nervous system: radiologic-pathologic
      correlation.
AB  - Pigmented lesions of the central nervous system (CNS) are a diverse group of
      entities that run the gamut from benign to malignant. These lesions may be well
      circumscribed or diffuse, and their imaging appearances are influenced by the
      degree of melanin content as well as the presence or absence of hemorrhage.
      Pigmented lesions include primary melanocytic lesions of the CNS and metastatic
      melanoma, as well as other CNS neoplasms that may undergo melanization, including
      schwannoma, medulloblastoma, and some gliomas. Primary melanocytic lesions of the
      CNS arise from melanocytes located within the leptomeninges, and this group
      includes diffuse melanocytosis and meningeal melanomatosis (seen in
      neurocutaneous melanosis), melanocytoma, and malignant melanoma. Primary melanin
      containing lesions of the CNS must be differentiated from metastatic melanoma
      because these lesions require different patient workup and therapy. Absence of a
      known primary malignant melanoma helps in the differential diagnosis, but an
      occult primary lesion outside the CNS must be sought and excluded. Pigmented
      lesions of the CNS are uncommon, and knowledge of their imaging characteristics
      and pathologic features is essential for their identification.

PMID- 19755609
TI  - Sacral chordoma.

PMID- 19755610
TI  - Bronchial atresia.

PMID- 19755611
TI  - Acceptability of adolescents' occlusion in Finnish municipal health centres with
      differing timing of orthodontic treatment.
AB  - The objective of the study was to compare the acceptability of occlusion among
      orthodontically treated and untreated adolescents in eight Finnish municipal
      health centres applying different timing of treatment. A random sample of 16- and
      18-year olds (n = 2325) living in these municipalities was invited for a clinical
      examination, and 1109 adolescents participated. Two calibrated orthodontists
      blindly examined the participants for the acceptability of occlusion with the
      Occlusal Morphology and Function Index. The history of orthodontic treatment was
      elicited by questionnaire. The impact of the history and timing of treatment on
      the acceptability of occlusion was analysed with logistic regression analysis.
      The history of orthodontic treatment decreased the odds for acceptability of
      morphology [odds ratio (OR) = 0.719, 95 per cent confidence limit (CL), P =
      0.016] and acceptability of function (OR = 0.724, 95 per cent CL, P = 0.018). The
      early timing of treatment increased the odds for acceptability of morphology (OR
      = 1.370, 95 per cent CL, P = 0.042) and of function (OR = 1.420, 95 per cent CL,
      P = 0.023). No substantial differences were observed in the acceptability of
      occlusion between the early and late timing health centres. However, the
      proportion of subjects with acceptable occlusion was slightly higher in the early
      than in the late timing group. These findings suggest that when examining the
      effect of timing on treatment outcome, factors other than acceptability of
      occlusion should be concomitantly evaluated. Consequently, in this context, the
      duration and cost of treatment need to be investigated.

PMID- 19755612
TI  - Symptomatic lower extremity vasculitis in giant cell arteritis: a case series.
AB  - OBJECTIVE: To describe the clinical features and outcomes of 19 patients with
      giant cell arteritis (GCA) and symptomatic lower extremity (LE) vasculitis.
      METHODS: We reviewed medical records of all patients diagnosed with GCA and
      symptomatic LE involvement between January 1, 1983, and June 30, 2007, for
      clinical features, laboratory and radiographic findings, and outcomes. RESULTS:
      From 6212 people evaluated for GCA at our institution between 1983 and 2007, we
      identified 19 cases of GCA with LE vasculitis, all women. Mean age at GCA
      diagnosis was 70 years (+/- standard deviation 7.99). Sixteen patients (84.2%)
      had LE symptoms preceding the diagnosis of GCA, median interval 3 months (range 1
      48). Three patients (15.8%) had GCA prior to developing LE claudication, median
      interval 16 months (range 9-34). Cranial symptoms were absent in 42.1%. No
      patient had permanent visual loss. Erythrocyte sedimentation rate (ESR) was
      elevated in 16 patients (84.2%), with median ESR 42.5 mm/h (range 8-103). Imaging
      studies revealed stenotic, occlusive, or aneurysmal disease that was frequently
      bilateral and consistent with vasculitis. The superficial femoral arteries were
      most commonly affected. Five patients (26.3%) had upper extremity involvement.
      Hypertension was the most common cardiovascular risk factor. All patients
      received glucocorticoid therapy, with clinical improvement in 15 patients (79%).
      Median length of followup was 41 months (range 11-180 mo). Five patients (26.3%)
      underwent LE revascularization surgery. Two patients required LE amputation and 1
      patient underwent toe amputation. Five patients received additional
      immunosuppressive therapy. CONCLUSION: Symptomatic LE vasculitis from GCA is
      rare. Patients typically present with rapidly progressive LE claudication and
      elevated inflammatory markers, while cranial symptoms may be absent. GCA with LE
      involvement is associated with significant morbidity; prompt diagnosis and
      treatment is essential.

PMID- 19755613
TI  - Randomized placebo-controlled crossover trial of tadalafil in Raynaud's
      phenomenon secondary to systemic sclerosis.
AB  - OBJECTIVE: Raynaud's phenomenon (RP) is an important clinical feature of systemic
      sclerosis (SSc) for which consistently effective therapies are lacking. The study
      was designed to assess the safety, tolerability, and efficacy of tadalafil, a
      selective, long acting type V cyclic GMP phosphodiesterase (PDE-5) inhibitor, in
      this clinical syndrome. METHODS: We performed a prospective, randomized, double
      blind, placebo-controlled, crossover study comparing oral tadalafil at a fixed
      dose of 20 mg daily for a period of 4 weeks versus placebo in women with RP
      secondary to SSc. RESULTS: Thirty-nine subjects completed the study and were
      evaluable. There were no statistically significant differences in Raynaud
      Condition Score (RCS), frequency of RP episodes, or duration of RP episodes
      between treatment groups. Placebo response was a confounding factor. Tadalafil
      was well tolerated. CONCLUSION: Tadalafil appears to be safe and well tolerated
      but lacks efficacy in comparison to placebo as a treatment for RP secondary to
      SSc.

PMID- 19755614
TI  - Phagocyte-specific S100A8/A9 protein levels during disease exacerbations and
      infections in systemic lupus erythematosus.
AB  - OBJECTIVE: S100A8 and S100A9 are calcium binding proteins of the S100 family
      highly expressed in neutrophils and monocytes. S100 proteins are novel ligands of
      TLR4 important in modulating inflammation. High levels of S100A8/A9 found in
      human inflammatory diseases are a marker of disease activity in rheumatoid
      arthritis (RA) and juvenile rheumatoid arthritis (JRA). We determined levels of
      S100A8/A9 in sera of patients with systemic lupus erythematosus (SLE) and
      analyzed their relation to clinical variables of disease activity. METHODS: A
      group of 93 patients with SLE were studied over a period of 3 years, and 143
      serum samples were analyzed. S100A8/A9 serum concentrations were determined by a
      sandwich ELISA. Sera from 10 primary Sjogren's syndrome (pSS) patients and 50
      healthy volunteers were used as controls. Correlations to SLEDAI, ANA, anti
      dsDNA, WBC, CH50, C4, and CRP were made. In addition, infections were recorded in
      all SLE patients. RESULTS: Serum levels of S100A8/A9 were significantly (p =
      0.04) higher in SLE patients (1412 +/- 664 ng/ml) versus healthy controls (339 +/
      35 ng/ml) and pSS patients (400 +/- 85 ng/ml). The only significant correlation
      (r = 0.219; p = 0.015) was found was between S100A8/A9 and SLEDAI. Further, SLE
      patients with concomitant infections had higher serum levels of S100A8/A9 (39300
      +/- 13375 ng/ml) than those without infections (1150 +/- 422 ng/ml). CONCLUSION:
      Serum levels of S100A8/A9 are significantly raised in SLE versus pSS patients and
      healthy controls and can be correlated to a disease activity index. S100A8/A9 is
      a more relevant marker of infection in SLE patients.

PMID- 19755615
TI  - Pattern of arterial calcification in patients with systemic lupus erythematosus.
AB  - OBJECTIVE: To evaluate the prevalence and pattern of arterial calcification in
      patients with asymptomatic systemic lupus erythematosus (SLE) compared with
      control subjects. SLE patients are prone to adverse cardiovascular events;
      however, the underlying atherosclerotic process is unknown. Multidetector
      computed tomography (MDCT) measured arterial calcium score (CS) reflecting
      underlying atherosclerosis and is closely associated with cardiovascular events.
      METHODS: Fifty age and sex matched SLE patients and controls were enrolled. All
      subjects underwent 64 slice MDCT scan to evaluate CS in coronary, carotid
      arteries and the aorta. RESULTS: As compared with controls, SLE patients had
      higher mean CS and prevalence of CS > 0 across all vascular beds. After
      adjustment for age and sex, SLE patient odds of having CS > 0 in any vascular bed
      was 33.6 (95% CI: 9.5-165.2) were higher versus patients in the control group,
      mainly due to more prevalent coronary calcification (OR 30.0, 95% CI: 6.7-203.8).
      In SLE patients, the most frequent vessel with CS > 0 was coronary (42%) followed
      by carotid artery (24%). Further, arterial calcification occurred early involving
      40% of SLE patients at age < 40 years, with increasing prevalence as age
      advanced. CONCLUSION: Our study confirms that patients with SLE have
      significantly higher prevalence and extent of systemic arterial calcification
      compared with age and sex matched controls.

PMID- 19755616
TI  - C-reactive protein gene polymorphisms in disease susceptibility and clinical
      manifestations of Korean systemic lupus erythematosus.
AB  - OBJECTIVE: C-reactive protein (CRP) is a sensitive marker of inflammation. It is
      hypothesized that polymorphism of CRP gene contributes to susceptibility to
      systemic lupus erythematosus (SLE). We tested this hypothesis by identifying CRP
      gene polymorphisms in Korean patients with SLE. METHODS: Approximately 1.5 kb of
      CRP promoter region was screened for single nucleotide polymorphism (SNP) using
      direct sequencing and 3 SNP in CRP exons by restriction fragment length
      polymorphism. The basal levels of CRP were measured by immunoturbidimetry. The
      effect of -390 C>A or T polymorphism on the promoter activity was analyzed by
      luciferase reporter assay in Hep3B cells. RESULTS: Allele frequency at
      polymorphisms within CRP promoter and exon in our Korean patients with SLE
      differed from that of Caucasians. The A allele was a major allele at position
      2043 in Korean SLE patients, whereas G is a major allele in Caucasian SLE. Our
      SLE patients had minor allele in the -390 polymorphism more frequently versus
      controls (p = 0.033). CRP 1185 polymorphism was associated with thrombocytopenia
      (p = 0.043). The basal levels of CRP were significantly higher in individuals who
      had minor allele in -390 and 2043 polymorphisms (p = 0.03. p = 0.024,
      respectively). Promoter-reporter construct carrying the -390 A or T allele
      displayed significantly higher promoter activity than that with the -390 C allele
      (p < 0.001). CONCLUSION: CRP gene -390 polymorphism plays a role in disease
      susceptibility of SLE through regulation of serum CRP level. Our results suggest
      that elevated basal CRP level may be important in the pathogenesis of SLE, even
      though CRP responsiveness to noninfectious inflammation of SLE is decreased.

PMID- 19755617
TI  - Test-retest reliability of patient global assessment and physician global
      assessment in rheumatoid arthritis.
AB  - OBJECTIVE: As a guide to treatment of rheumatoid arthritis (RA), physicians use
      measurement tools to quantify disease activity. The Patient Global Assessment
      (PGA) asks a patient to rate on a scale how they feel overall. The Physician
      Global Assessment (MDGA) is a similar item completed by the assessing physician.
      Both these measures are frequently incorporated into other indices. We studied
      reliability characteristics for global assessments and compared test-retest
      reliability of both the PGA and the MDGA, as well as other commonly used measures
      in RA. METHODS: We studied 122 patients with RA age 17 years or older. Patients
      who received steroid injection or change in steroid dose at the visit were
      excluded. Patients completed the HAQ, PGA, visual analog scale for pain (VAS
      Pain), VAS Fatigue, and VAS Sleep. After seeing their physician, they received
      another questionnaire to complete within 2 days at the same time of day as clinic
      visit. Physicians completed the MDGA at the time of the patient's appointment and
      at the end of their clinic day. Test-retest results were assessed using
      intraclass correlations (ICC). "Substantial" reliability is between 0.61-0.80 and
      "almost perfect" > 0.80. RESULTS: Four rheumatologists and 146 patients
      participated, with 122 questionnaires returned (response rate 83.6%). Test-retest
      reliability was 0.702 for PGA, 0.961 for MDGA, and 0.897 for HAQ; VAS results
      were 0.742 for Pain, 0.741 for Fatigue, and 0.800 for Sleep. The correlation
      between PGA and MDGA was -0.172. CONCLUSION: PGA, MDGA, HAQ, and VAS Pain, VAS
      Fatigue, and VAS Sleep all showed good to excellent test-retest reliability in
      RA. MDGA was more reliable than PGA. The correlation between PGA and MDGA was
      poor.

PMID- 19755618
TI  - Tenofovir-emtricitabine-efavirenz in HIV-I-infected adults in Senegal: a 96-week
      pilot trial in treatment-naive patients.
AB  - We report the results of a pilot open-label trial of a tenofovir
      (TDF)/emtricitabine (FTC)/efavirenz (EFV) combination conducted in Dakar,
      Senegal. Forty HIV-1-infected patients, naive of antiretroviral treatment and
      without active opportunistic disease, were included and followed through 96
      weeks. At weeks 48 and 96, respectively, 82.5% and 85% of patients had HIV-1 RNA
      <400 copies/mL (72.5% and 77.5% with HIV-1 RNA <50 copies/mL). Between baseline
      and week 96, the mean (SD) CD4 count increased from 126 (102) to 338 (155)
      cells/mm(3). The mean (SD) creatinine clearance decreased from 92 (36) to 73 (19)
      mL/min (P = .001). Treatment adherence was at least 94% at all scheduled visits.
      The efficacy and tolerability of a TDF/FTC/EFV combination were high and similar
      to those observed in Northern countries. This drug combination can be recommended
      in limited-resource countries, as did the World Health Organization (WHO) and
      should be made readily available as a fixed-dose combination.

PMID- 19755619
TI  - Epidemiology of opportunistic infections and its correlation with CD4 T
      lymphocyte counts and plasma viral load among HIV-positive patients at a tertiary
      care hospital in India.
AB  - The study was conducted to find the correlation of CD4 counts and plasma viral
      load (PVL) with opportunistic infections (OIs) in HIV-positive patients. A total
      of 43 drug-naive patients enrolled in the study. Absolute CD4 counts and PVL were
      measured. On the basis of symptoms, sputum, stool, and blood samples were
      obtained for laboratory tests. Oral swabs were obtained from all the patients.
      Pneumocystis jiroveci pneumonia was found in 45.2% patients (odds ratio [OR] =
      12.8 for CD4 counts <or=100 cells/ mm(3) and 8.5 for PVL >4.0 log(10) copies/mL).
      Pulmonary tuberculosis (TB; OR = 8.0 for PVL >4.0 log(10) copies/mL) and
      streptococcal pneumonia (detected only with CD4 counts <50 cells/mm( 3) and PVL
      >4.0 log(10) copies/mL) were seen in 41.9% and 12.9% patients, respectively.
      Among patients with diarrhea, Giardia lamblia was detected in 31% patients (OR =
      3.0 for CD4 counts <or=100 cells/mm(3) and 4.0 for PVL >4.0 log(10) copies/mL)
      and Cryptosporidium in 17.2% patients (OR = 1.8 for CD4 counts <or=100
      cells/mm(3) and found only with PVL >4.0 log(10) copies/mL). Shigellosis and
      Clostridium difficile toxin was present in 13.6% patients and 6.8% patients,
      respectively.

PMID- 19755620
TI  - Delivery of antifungal agents using bioactive and nonbioactive bone cements.
AB  - BACKGROUND: Management of fungal osteomyelitis is prolonged and frequently
      unsuccessful. Antifungal-impregnated cement is sometimes used as adjunctive
      therapy. OBJECTIVE: To examine the release of antifungals from biodegradable and
      nonbiodegradable cement carriers. METHODS: In vitro methods were used to assess
      antifungal drug release and antifungal activity of impregnated cements commonly
      used as adjunctive treatment of osteomyelitis. Cements included thermoplastic,
      nonbioactive polymers (polymethylmethacrylate [PMMA]) or bioactive agents
      (hydroxyapatite [HAP], beta-tricalcium phosphate [beta-TCP]) and were formed into
      spheres (beads). RESULTS: Amphotericin B provided consistent supernatant
      concentrations (release), between 1.75 and 2.0 microg/mL, over 110 days from all
      bone cements. Flucytosine and fluconazole were observed for 33-42 days before
      becoming undetectable from a nonbioactive sphere and 18-22 days from a bioactive
      sphere. Serum concentrations for micafungin, terbinafine, and anidulafungin
      impregnated into PMMA rapidly became undetectable, regardless of the matrix used.
      Investigational beta-TCP spheres prolonged release for fluconazole and
      micafungin, but had no effect on amphotericin B. Serum calcium concentrations
      decreased 60-80% in all HAP-impregnated drug sphere supernatants. Only
      amphotericin B-impregnated PMMA impacted supernatant calcium, decreasing
      concentrations by 50-60%. The antifungal-impregnated beads did not appear to be
      toxic to osteoblasts during 72 hours of exposure in tissue culture medium.
      CONCLUSIONS: Elution characteristics of most antifungals from bone cement spheres
      are probably not optimal for treatment of deep-seated fungal infections if a
      similar phenomenon of antifungal release manifests in vivo. Ceramic nonabsorbable
      impregnated devices must be removed after their lifespan expires and may
      necessitate another surgical procedure that can increase surgical risk and cost.
      Bioactive osteoconductive materials may provide a surgical alternative to
      nonabsorbable matrices. However, there have been no controlled trials
      demonstrating improved therapeutic outcomes with local therapy and assessing
      whether biodegradable materials act as a new focus for infection.

PMID- 19755621
TI  - Successful use of dexmedetomidine for sedation in a 24-week gestational age
      neonate.
AB  - OBJECTIVE: To describe a case of dexmedetomidine use for sedation in a 24-week
      gestational age premature neonate. CASE SUMMARY: A 9-day-old, 24-week gestational
      age male neonate on high-frequency oscillatory mechanical ventilation was
      experiencing severe agitation refractory to high-dose intravenous narcotics and
      benzodiazepines. Since the infant's respiratory stability was reliant on adequate
      sedation, he was given dexmedetomidine after several days of suboptimal response
      to escalation of standard agents. Treatment prior to dexmedetomidine included
      continuous-infusion fentanyl 10 microg/kg/h, intravenous lorazepam 0.6 mg/kg
      every 4 hours, intermittent doses of both lorazepam and midazolam as needed, and
      a single bolus dose of phenobarbital. The patient calmed markedly during the
      dexmedetomidine loading dose infusion and remained adequately sedated while the
      drug was continued. The dexmedetomidine infusion allowed weaning of mechanical
      ventilation settings and eventual extubation of the infant, as well as rapid
      tapering of other sedative medications. The maximum dexmedetomidine infusion rate
      was 0.7 microg/kg/h, and total duration of therapy was 19 days. No significant
      adverse effects were directly attributed to dexmedetomidine use during this time.
      DISCUSSION: Dexmedetomidine is a novel alpha(2)-agonist approved for short-term
      sedation in mechanically ventilated adults. Data describing its use in pediatric
      and neonatal patients continue to emerge. The prolonged use of dexmedetomidine in
      very-low-birth-weight neonates has not been described in the literature.
      CONCLUSIONS: Dexmedetomidine was an effective sedative and analgesic in a 24-week
      gestational age neonate treated for refractory agitation while on mechanical
      ventilation. Based on its documented efficacy for pain and sedation and its
      favorable adverse effect profile, dexmedetomidine warrants further study as first
      line or adjunct therapy with narcotics for sedation in ventilated newborns.

PMID- 19755622
TI  - Acute interstitial nephritis associated with linezolid.

PMID- 19755623
TI  - Morphine-induced muscle rigidity in a term neonate.
AB  - OBJECTIVE: To describe a potentially fatal adverse drug event after
      administration of morphine to a term neonate. CASE SUMMARY: A 2-day-old term
      neonate experienced generalized muscle rigidity and laryngeal spasm resulting in
      acute respiratory failure on 2 separate occasions after morphine administration.
      The first occasion was after administration of bolus doses of fentanyl and
      morphine 100 microg/kg in the operating theater; administration of intravenous
      propofol 2 mg/kg resulted in relief of muscle rigidity. The second occasion
      occurred a few hours later, when the patient received a continuous infusion of
      morphine 4.4 microg/kg/h in the intensive care unit and experienced generalized
      muscle rigidity with respiratory compromise. The opioid antagonist naloxone 30
      microg/kg was administered intravenously, which immediately resulted in a patent
      airway and spontaneous breathing. An objective causality assessment using the
      Naranjo probability scale revealed that the likelihood of morphine causing the
      patient's muscle rigidity on the second occasion was highly probable to definite.
      It is not clear whether the first occurrence of muscle rigidity was morphine
      induced. DISCUSSION: We searched PubMed and EMBASE (through August 2009) for
      previous reports of morphine-related muscle rigidity and/or laryngeal spasm,
      using the search terms (muscle rigidity OR chest rigidity OR laryngeal spasm) AND
      (morphine OR fentanyl OR opioid). Sudden onset of muscle rigidity and laryngeal
      spasm is described in the literature as a rare but serious adverse event after
      infusion of fentanyl and similar opioids in both adults and young infants.
      However, there are no reports of this potentially fatal adverse event after
      administration of morphine. To our knowledge this is the first case reported of
      life-threatening muscle rigidity and laryngeal spasm after therapeutic doses of
      morphine in humans. CONCLUSIONS: A serious adverse event consisting of
      generalized muscle rigidity and laryngospasm can occur after bolus administration
      of morphine as well as during continuous infusion. Clinicians should be aware of
      this possibility.

PMID- 19755624
TI  - Evidence-based treatment options for the management of skin toxicities associated
      with epidermal growth factor receptor inhibitors.
AB  - OBJECTIVE: To compile evidence from randomized controlled trials, case series,
      and case reports to identify the effectiveness of various therapeutic agents for
      the treatment and prevention of dermatologic effects secondary to epidermal
      growth factor receptor inhibitor (EGFRI) administration. DATA SOURCES: Literature
      was accessed through PubMed (2002-May 2009) and Scopus (2002-March 2009), using
      the terms epidermal growth factor receptor inhibitor, cetuximab, erlotinib,
      gefitinib, panitumumab, management, skin toxicity, and cutaneous effects. In
      addition, reference citations from publications identified were reviewed. STUDY
      SELECTION AND DATA EXTRACTION: An evaluation of published clinical trials, case
      series, case reports, and clinical management guidelines that studied the
      treatment options for EGFRI-induced skin toxicities was performed. Studies that
      reported dosing regimens and treatment outcomes were included in this review.
      DATA SYNTHESIS: Management of EGFRI-induced skin toxicities has been documented
      in 2 randomized controlled trials, 3 case series, and 10 case reports in a total
      of 156 patients. There is strong evidence for the use of topical antibiotics to
      manage EGFRI skin toxicities. Controversy exists regarding the use of
      corticosteroids and retinoids for the management of EGFRI-induced rash. Several
      variables are noted among the number of case series and case reports, such as
      follow-up duration of the intervention, making any comparisons difficult.
      CONCLUSIONS: Overall, antibiotics are the most common treatment option and have
      the potential to reduce the severity of skin rash. Well-designed clinical studies
      with proper recording of relevant data on the management of EGFRI-induced
      dermatologic effects are needed to properly evaluate the use of various
      therapeutic agents. Apart from randomized controlled trials, comprehensive case
      reports are also important for clinical evaluation on a case-by-case basis.

PMID- 19755625
TI  - Increase in plasma endotoxin concentrations and the expression of Toll-like
      receptors and suppressor of cytokine signaling-3 in mononuclear cells after a
      high-fat, high-carbohydrate meal: implications for insulin resistance.
AB  - OBJECTIVE: To compare the effect of a high-fat, high-carbohydrate meal (HFHC)
      with that of a high-fiber and fruit meal on the concentrations of endotoxin
      (lipopolysaccharide [LPS]), LPS-binding protein (LBP), the expression of toll
      like receptors (TLRs), and the suppressor of cytokine signaling-3 (SOCS-3) in
      mononuclear cells. RESEARCH DESIGN AND METHODS: Healthy lean subjects were given
      910 calories of either an HFHC meal (n = 10) or an American Heart Association
      (AHA)-recommended meal rich in fiber and fruit (n = 10) after an overnight fast.
      Blood was collected before and at 1, 2, and 3 h after the meal. Cellular indexes
      of oxidative and inflammatory stress; the expression of SOCS-3, TLR2, and TLR4 in
      mononuclear cells; and plasma concentrations of LPS and LBP were measured.
      RESULTS: HFHC meal intake induced an increase in plasma LPS concentration and the
      expression of SOCS-3, TLR2, and TLR4 protein, reactive oxygen species generation,
      and nuclear factor-kappaB binding activity (P < 0.05 for all). These increases
      were totally absent after the AHA meal rich in fiber and fruit. CONCLUSIONS: The
      novel changes described after the HFHC meal elucidate further the mechanisms
      underlying postprandial inflammation and also provide the first evidence
      explaining the pathogenesis of insulin and leptin resistance mediated by SOCS-3
      after such meals. In contrast, an AHA meal does not induce these effects.

PMID- 19755626
TI  - Trends in diabetes prevalence and diabetes-related complications in older Mexican
      Americans from 1993-1994 to 2004-2005.
AB  - OBJECTIVE: Evidence has shown that Mexican Americans have a higher prevalence of
      diabetes and a greater risk for diabetes-related complications than non-Hispanic
      whites. However, no studies have described the changes in prevalence among older
      Mexican Americans. The purpose of this study was to expand on the current
      literature by examining the trends in diabetes prevalence and diabetes-related
      complications in Mexican Americans aged >or=75 years from 1993-1994 to 2004-2005.
      RESEARCH DESIGN AND METHODS: The prevalences of self-reported diabetes and
      diabetes-related complications were estimated in the original cohort (1993-1994)
      and the new cohort (2004-2005) of the Hispanic Established Population for the
      Epidemiologic Study of the Elderly (Hispanic EPESE) and were compared across the
      two surveys. RESULTS: The prevalence of diabetes among Mexican Americans aged
      >or=75 years has nearly doubled between 1993-1994 and 2004-2005 from 20.3 to
      37.2%, respectively (P < 0.001). The increase in the prevalence of diabetes was
      similar across all sociodemographic factors. Diabetes complications did not
      change significantly between the two cohorts. However, the prevalence of having
      any lower-extremity function disability did increase between the two cohorts.
      CONCLUSIONS: The prevalence of diabetes in older Mexican Americans has increased
      dramatically. At the same time, there has been no improvement in diabetes-related
      complications as has been found in the general older population. These findings
      heighten the urgency for more effective public health interventions targeted to
      this population. As diabetes and obesity become more prevalent in older adults,
      physicians should encourage appropriate management in older patients, including
      early detection and glycemic control.

PMID- 19755627
TI  - Cross-sectional validation of diabetes risk scores for predicting diabetes,
      metabolic syndrome, and chronic kidney disease in Taiwanese.
AB  - OBJECTIVE: To validate the performance of current diabetes risk scores (DRSs)
      based on simple clinical information in detecting type 2 diabetes, metabolic
      syndrome (MetSyn), and chronic kidney disease (CKD). RESEARCH DESIGN AND METHODS:
      The performance of 10 DRSs was evaluated in a cross-sectional population
      screening of 2,759 Taiwanese subjects. RESULTS: All DRSs significantly correlated
      with measures of insulin resistance, estimated glomerular filtration rate, and
      urine albumin excretion. The prevalence of screening-detected diabetes (SDM),
      MetSyn, and CKD increased with higher DRSs. For prediction of SDM, the Cambridge
      DRS by Griffin et al. and the Finnish DRS outperformed other DRSs in terms of
      discriminative power and model fit. For prediction of MetSyn and CKD, the
      Atherosclerosis Risk in Community Study score by Schmidt et al. outperformed
      other DRSs. CONCLUSIONS: Risk scores based on simple clinical information are
      useful to identify individuals at high risk for diabetes, MetSyn, and CKD in
      different ethnic populations.

PMID- 19755628
TI  - Intimate partner violence and social isolation across the rural/urban divide.
AB  - Intimate partner violence (IPV) is a pervasive social problem that affects
      victims, families, and communities. Beginning with the acknowledgment of this
      phenomenon as a social problem, investigations have attempted to answer questions
      regarding the extent, prevalence, and the possible contributing social and
      psychological factors that influence this behavior. This study proposes an
      approach to the problem of IPV based on a unifying concept: social isolation. The
      authors argue that the utility of the concept of social isolation lies in its
      ability to encapsulate critical social-structural and social-psychological
      correlates of IPV. The main objective of the study is to examine the extent to
      which the role of social isolation in predicting IPV varies by urban/rural
      context. Measures of key variables were obtained from Waves 1 and 2 of the
      National Survey of Families and Households and the 1990 census. Results of
      multivariate analyses indicate that only some measures of social support
      (isolation) are statistically significant and only for families within rural
      (nonmetropolitan) counties.

PMID- 19755629
TI  - Religious care required for Japanese terminally ill patients with cancer from the
      perspective of bereaved family members.
AB  - The aim of this study was to explore the most suitable religious care for
      Japanese terminally ill patients with cancer based on the opinions of bereaved
      family members. A multicenter questionnaire survey on palliative care service was
      sent to 592 bereaved family members of patients with cancer who were admitted to
      palliative care units in Japan, and 430 responded by mail. In the section of the
      questionnaire about religious care, 382 responses were used for quantitative
      analysis, and 71 responses about religious care for qualitative analysis. In the
      current study, the 71 responses were grouped into families with and without a
      religion and were analyzed qualitatively. Families with a religion (N = 28) chose
      answers such as ''Instrumental care'' such as music or a religious event,
      ''Freedom of choice of kinds for religious care,'' ''Staff involvement of
      religious care,'' ''Meeting with a pastoral care workers,'' and ''Burden of
      offering a different kind of personal religion.'' In contrast, families without a
      religion (N = 44) chose answers such as ''Instrumental care,'' ''Freedom of
      choice whether patients receive religious care or not,'' ''Spiritual care,''
      ''Not being able to accept religious care,'' and ''Burden of thinking about a
      religion and nuisance.'' These findings suggest that Japanese bereaved families
      with a religion generally regard religious care positively and prefer care
      through their own religion, whereas some families without a religion require
      religious care but some do not prefer it.

PMID- 19755630
TI  - The blessing of hospice.
AB  - Hospice care is provided at the end of life. End-of-life care is not discussed
      until it is needed. The average person knows the term but not what it really
      means until a terminal diagnosis is made. This article discusses the end-of-life
      issues faced by our mother and how it affected the entire family. The hospice
      home our mother lived in during the last 2 weeks and 1 day of her life showcased
      the best hospice has to offer in terms of physical, emotional, and spiritual
      support.

PMID- 19755631
TI  - The association of body mass index with health outcomes: causal, inconsistent, or
      confounded?
AB  - According to the definition of confounding in a causal diagram, the association
      of body mass index (weight (kg)/height (m)(2)) with health-related outcomes is
      almost always noncausal, attributable to confounding by weight and perhaps
      height. The same conclusion holds for any other deterministic derivation from
      weight and height. No causal knowledge is gained by estimating a nonexistent
      effect of body mass index.

PMID- 19755633
TI  - Using time-dependent covariate analysis to elucidate the relation of smoking
      history to Warthin's tumor risk.
AB  - The authors aimed to elucidate the relation of the time-dependent smoking history
      parameters--age at smoking initiation and smoking intensity, duration, and
      latency--to the risk of Warthin's tumor, a benign tumor of the salivary gland for
      which cigarette smoking is a strong risk factor. They studied 117 cases of
      Warthin's tumor and 336 matched controls included in an Israeli nationwide case
      control study of parotid gland tumors conducted from 2002 to 2003 by using the
      Cox regression model with time-dependent covariates, with age as the time axis.
      When current age and smoking duration were included in the statistical model, the
      authors show that the coefficient of a latency variable does not represent
      latency as such, but a balancing of the effects of age at initiation and time
      since cessation. They found a strong positive linear effect of duration of
      smoking, together with a positive nonlinear effect of intensity that levels off
      at higher intensities, and a negative effect of latency from 25 years onward. The
      latter finding implies that the effect of time since cessation dominates the
      effect of age at initiation, with risk decreasing sharply after smoking
      cessation. The relation of smoking variables to Warthin's tumor agrees with the
      patterns reported for lung cancer.

PMID- 19755634
TI  - Re: "Determinants of quality of interview and impact on risk estimates in a case
      control study of bladder cancer".

PMID- 19755635
TI  - Invited Commentary: Causal diagrams and measurement bias.
AB  - Causal inferences about the effect of an exposure on an outcome may be biased by
      errors in the measurement of either the exposure or the outcome. Measurement
      errors of exposure and outcome can be classified into 4 types: independent
      nondifferential, dependent nondifferential, independent differential, and
      dependent differential. Here the authors describe how causal diagrams can be used
      to represent these 4 types of measurement bias and discuss some problems that
      arise when using measured exposure variables (e.g., body mass index) to make
      inferences about the causal effects of unmeasured constructs (e.g., "adiposity").
      The authors conclude that causal diagrams need to be used to represent biases
      arising not only from confounding and selection but also from measurement.

PMID- 19755636
TI  - Tumor necrosis factor polymorphisms and alcoholic liver disease: a HuGE review
      and meta-analysis.
AB  - The association between alcoholic liver disease (ALD) and tumor necrosis factor
      alpha gene (TNFA) polymorphisms has been analyzed in several studies, but results
      have been conflicting. The main purpose of this study was to integrate previous
      findings and explore whether these polymorphisms are associated with
      susceptibility to ALD. The authors surveyed studies on the relation between TNFA
      gene polymorphisms and ALD by means of an electronic database search. A meta
      analysis was conducted in a random-effects model. The association between ALD and
      the -238G>A or -308G>A polymorphism of the TNFA gene has been analyzed in 11
      studies. Concerning the -238G>A polymorphism, the authors found a significant
      association between possession of the A allele and risk of alcoholic liver
      cirrhosis (odds ratio = 1.47, 95% confidence interval: 1.05, 2.07). Meta-analysis
      of the relation between the -308G>A polymorphism and ALD did not show any
      significant association. Given the limited number of studies and the potential
      biases, more data are needed to confirm the association described for the -238A
      allele.

PMID- 19755637
TI  - Relationship of word- and sentence-level working memory to reading and writing in
      second, fourth, and sixth grade.
AB  - PURPOSE: The purpose of this study was to evaluate the contribution of working
      memory at the word and sentence levels of language to reading and writing
      outcomes. METHOD: Measures of working memory at the word and sentence levels,
      reading and writing, were administered to 2nd (N = 122), 4th (N = 222), and 6th
      (N = 105) graders. Structural equation modeling was used to evaluate whether the
      2 predictor working memory factors contributed unique variance beyond their
      shared covariance to each of 5 outcome factors: handwriting, spelling, composing,
      word reading, and reading comprehension. RESULTS: At each grade level, except for
      handwriting and composing in 6th grade, the word-level working memory factor
      contributed unique variance to each reading and writing outcome. The text-level
      working memory factor contributed unique variance to reading comprehension in 4th
      and 6th grade. DISCUSSION: The clinical significance of these findings for
      assessment and intervention is discussed.

PMID- 19755638
TI  - Incorporating computer-aided language sample analysis into clinical practice.
AB  - PURPOSE: During the evaluation of language abilities, the needs of the child are
      best served when multiple types and sources of data are included in the
      evaluation process. Current educational policies and practice guidelines further
      dictate the use of authentic assessment data to inform diagnosis and treatment
      planning. Language sampling and analysis (LSA) offers an important clinical tool
      for gathering such authentic assessment data, and computer-aided methods of LSA
      make it clinically feasible. The purpose of this tutorial is to provide step-by
      step procedures for computer-aided LSA (CLSA). METHOD: This tutorial includes
      instructions for a 4-step CLSA process: (a) eliciting a representative sample of
      the child's language and recording it directly onto the computer; (b)
      transcribing the language sample; (c) analyzing the language sample and
      interpreting the results using a readily available software program, Systematic
      Analysis of Language Transcripts (SALT; J. Miller & A. Iglesias, 2006); and (d)
      using the results to plan the child's treatment goals and activities. A case
      study is provided to illustrate this process. IMPLICATIONS: Digital technologies
      can dramatically improve the feasibility of LSA, potentially transforming
      clinical practice by providing a quantifiable but naturalistic measure of
      language. This tutorial will facilitate the integration of useful technologies
      into clinical practice and provide information regarding the application of CLSA
      data.

PMID- 19755639
TI  - Clinical application of the mean babbling level and syllable structure level.
AB  - PURPOSE: This clinical exchange reviews two independent phonological assessment
      measures: mean babbling level (MBL) and syllable structure level (SSL). Both
      measures summarize phonetic inventory and syllable shape in a calculated average
      and have been used in research to describe the phonological abilities of children
      ages 9 to 36 months. An example of the measures' clinical use is presented.
      METHOD: Six studies reporting MBL and SSL were reviewed. Combined, the studies
      included 207 participants. One hundred twenty-eight of those were developing
      language as expected, and 79 were identified as having speech-language
      impairment. CONCLUSION: Overall, the studies indicate that SSL is a reliable
      measure that increases as children develop. Children with language impairment
      exhibit lower SSL scores than children with typical language skills. Further, a
      lower than expected MBL is predictive of a lack of meaningful speech at 24 months
      of age. IMPLICATION: MBL and SSL have clinical application in terms of initial
      evaluation as well as progress monitoring. Recommendations for standardized
      corpus inclusion procedures are presented.

PMID- 19755640
TI  - Family quality of life following early identification of deafness.
AB  - PURPOSE: Family members' perceptions of their quality of life were examined
      following early identification of deafness in children. METHOD: A questionnaire
      was used to solicit ratings of satisfaction from the family members of 207
      children who were deaf and younger than 6 years of age. RESULTS: Results
      indicated that families were generally satisfied with the areas of family life
      surveyed. Descriptive analysis suggested lower satisfaction ratings in the area
      of emotional well-being. Families also reported that their child's deafness had
      the largest impact on their emotional well-being. Family members of children
      using oral communication with a cochlear implant reported higher satisfaction
      with their child's speech production and perception outcomes than family members
      of children using hearing aids alone. IMPLICATIONS: We recommend that service
      providers and early hearing detection and intervention program coordinators
      consider additional supports for family well-being following the early
      identification of deafness in children.

PMID- 19755641
TI  - What makes a caseload (un)manageable? School-based speech-language pathologists
      speak.
AB  - PURPOSE: Large caseload sizes and a shortage of speech-language pathologists
      (SLPs) are ongoing concerns in the field of speech and language. This study was
      conducted to identify current mean caseload size for school-based SLPs, a
      threshold at which caseload size begins to be perceived as unmanageable, and
      variables contributing to school-based SLPs' feelings of caseload manageability.
      METHOD: Approximately 2,000 public-school-based SLPs from across the country were
      solicited to participate in an online, Web-based survey between April and May of
      2007. Of those SLPs who were contacted, 634 full-time SLPs from 49 states
      completed the survey. The data were evaluated using descriptive statistics and
      logistic regression. RESULTS: The mean caseload size for SLPs in this study was
      49 students. At the caseload range of 41-50 students, approximately 60% of the
      SLPs perceived their caseload size as unmanageable. Logistic regression revealed
      caseload size, years of experience, and extent of collaboration as significant
      predictors of an SLP's likelihood of feeling that his or her caseload size is
      manageable. CONCLUSIONS: Caseload size continues to be an area of concern for
      school-based SLPs, and efforts to address this problem must continue in order to
      prevent long-term struggles with SLPs' dissatisfaction, shortages, and turnover.
      Policy, research, and clinical implications are discussed.

PMID- 19755642
TI  - The early years of language, speech, and hearing services in u.s. Schools.
AB  - PURPOSE: This article focuses on various aspects of the beginnings of speech
      therapy offerings in America's public schools. It traces the pioneering
      professionals and significant milestones associated with diagnostic and therapy
      practices during the late 19th and early 20th century. The aim is to uncover the
      neglected history of public school speech therapy practices and to show how the
      practices of yesterday compare with those of today. METHOD: Historical documents
      were analyzed to discover the key contributors and locations of the first public
      school speech-pathology programs. The analysis also traces the populations that
      were served and the professional training of the early practitioners, as well as
      their therapy and service delivery practices. CONCLUSIONS: Between 1895 and 1921,
      most of the major cities in the United States had hired their first speech
      clinicians. Between 1921 and 1930, many cities expanded their programs and were
      hiring supervisors to coordinate these services. These early clinicians carved
      out some now-familiar practices. Comparing what they did and when and how they
      did it with today's practices can offer school clinicians of today a sense of
      their own history and identity. Such an understanding can also provide insights
      about some of today's taken-for-granted practices.

PMID- 19755643
TI  - Aberrant methylation of RASSF1A in plasma DNA before breast cancer diagnosis in
      the Breast Cancer Family Registry.
AB  - In addition to classic genetic mechanisms such as deletions and mutations, growth
      regulatory genes can be inactivated via methylation of cytosine-residues in their
      promoter regions. Hypermethylation of promoter CpG islands is now recognized as
      an important and early event in carcinogenesis. Detection of methylated DNA in
      serum or plasma has been suggested to be a marker for early cancer development.
      We examined methylation changes in RASSF1A, a growth regulatory gene in plasma
      DNA from blood collected before diagnosis from women with breast cancer and from
      controls. Samples were from two sets of subjects, 28 women with breast cancer and
      10 of their unaffected siblings, and 33 women with breast cancer and 29 age- and
      ethnicity-matched population-based controls. Using methylation specific PCR, we
      found 11 of 61 (18%) cases were positive for methylation of RASSF1A in their
      plasma DNA collected before diagnosis. Two of 10 healthy high-risk sibling
      controls (20%) had plasma DNA positive for RASSF1A methylation in their plasma
      DNA compared with 0 of 29 (0%) population-based controls. Tumor tissue was
      available for 12 cases and all were positive for RASSF1A methylation. These
      results, if replicated, suggest that aberrant promoter hypermethylation in
      serum/plasma DNA may be common among high-risk women and may be present years
      before cancer diagnosis.

PMID- 19755644
TI  - Obesity and cancer: the role of dysfunctional adipose tissue.
AB  - Overweight and obesity are health problems of epidemic proportions, increasing
      the risk not only of cardiovascular disease and type 2 diabetes mellitus but also
      of various types of cancer. Obesity is strongly associated with changes in the
      physiological function of adipose tissue, leading to insulin resistance, chronic
      inflammation, and altered secretion of adipokines. Several of these factors, such
      as insulin resistance, increased levels of leptin, plasminogen activator
      inhibitor-1, and endogenous sex steroids, decreased levels of adiponectin, and
      chronic inflammation, are involved in carcinogenesis and cancer progression. This
      article reviews these mechanisms, focusing on adipose tissue dysfunction as a
      unifying causal factor. Although understanding of the link between obesity and
      cancer might provide therapeutic targets, preventing overweight and obesity still
      remains number one priority.

PMID- 19755645
TI  - Sexually transmitted infections and prostate cancer among men in the U.S.
      military.
AB  - Studies of self-reported sexually transmitted infections (STI) suggesting an
      association with prostate cancer may reflect underreporting of such infections
      among nondiseased subjects. To reduce such bias, we studied archived sera in a
      cohort of U.S. military personnel known to have high rates of both STIs and
      prostate cancer. Using a nested case-control design, serum samples from 534 men
      who served on active duty between September 1, 1993 and September 1, 2003 were
      examined. Controls were individually matched to cases based on date of serum
      collection, date of birth, branch of service, military rank, marital status, and
      race. Each of the 267 case-control pairs had two serum samples: a recent serum
      sample, taken approximately 1 year before the case's prostate cancer diagnosis,
      and an earlier serum sample, taken approximately 8 years before diagnosis. Each
      serum specimen was studied for antibodies against human papillomavirus, herpes
      simplex virus-2 (HSV-2), and Chlamydia trachomatis. Logistic regression accounted
      for matching and potential confounding factors. Study data indicated no
      association between prostate cancer and serologic evidence of infections just
      before the reference date. However, a statistically significant association
      between prostate cancer and serologic evidence of HSV-2 infection was detected in
      the earlier sample (odds ratio, 1.60; 95% confidence interval, 1.05-2.44). The
      strength of this association increased when analyses were restricted to sera
      collected at least 60 months before diagnosis (odds ratio, 2.04; 95% confidence
      interval, 1.26-3.29; 204 pairs). If this association is causal, then our findings
      would suggest a long latency period for prostate cancer development after HSV-2
      infection.

PMID- 19755646
TI  - An experimental test of the effect of incentives on recruitment of ethnically
      diverse colorectal cancer cases and their first-degree relatives into a research
      study.
AB  - BACKGROUND: Optimizing participant response rates is important for obtaining
      representative samples and the timely completion of studies. It is a common
      practice to use participant incentives to boost response rates, but few studies
      have systematically examined their effectiveness, particularly among minority
      groups. METHODS: We experimentally tested three incentive strategies for their
      effectiveness in improving response rates among colorectal cancer cases (n =
      3,816) and their relatives (n = 2,353). A 2 x 2 x 2 factorial design compared (a)
      registered versus first class mail, (b) $5 cash with the initial mailing
      (yes/no), and (c) $20 promise (yes/no) upon completion of the information form
      (for cases) or $10 promise (yes/no) upon completion of the baseline survey (for
      relatives). Outcome measures were provision of contact information on first
      degree relatives for cases and completion of the baseline survey for relatives.
      RESULTS: The response rate among cases was low in all ethnic groups (28-37%) and
      incentive strategies did not have an effect. Among relatives, the overall
      baseline survey response rate was 71%, ranging from 66% among Asians to 76% among
      Whites. Modest absolute increases were observed for payment schedules that
      included a $5 cash enclosure with the initial mailing in the total sample [odds
      ratio (OR), 1.65 and 1.47] and among Latinos (OR, 1.94 and 1.74) but not among
      Asians (OR, 1.61 and 1.55) or African Americans (OR, 1.19 and 1.02). Response
      rates were not influenced by registered versus first-class mailing. CONCLUSION:
      The effects of incentives in this study were modest with some suggestion of
      differences by ethnic group and type of incentive.

PMID- 19755647
TI  - Cyclooxygenase-2 polymorphisms, aspirin treatment, and risk for colorectal
      adenoma recurrence--data from a randomized clinical trial.
AB  - Cyclooxygenase-2 (COX-2) catalyzes the rate-limiting step in the production of
      prostaglandins, potent mediators of inflammation. Chronic inflammation plays an
      important role in the development and progression of colorectal cancer. Aspirin
      inhibits COX-2 activity and lowers the risk for colorectal adenomas and cancer.
      We investigated whether common genetic variation in COX-2 influenced risk for
      colorectal adenoma recurrence among 979 participants in the Aspirin/Folate Polyp
      Prevention Study who were randomly assigned to placebo or aspirin and followed
      for 3 years for the occurrence of new adenomas. Of these participants, 44.2%
      developed at least one new adenoma during follow-up. Adjusted relative risks and
      95% confidence intervals (95% CI) were calculated to test the association between
      genetic variation at six COX-2 single-nucleotide polymorphisms and adenoma
      occurrence and interaction with aspirin treatment. Two single-nucleotide
      polymorphisms were significantly associated with increased adenoma recurrence:
      for rs5277, homozygous carriers of the minor C allele had a 51% increased risk
      compared with GG homozygotes (relative risk, 1.51; 95% CI, 1.01-2.25), and for
      rs4648310, heterozygous carriers of the minor G allele had a 37% increased risk
      compared with AA homozygotes (relative risk, 1.37; 95% CI, 1.05-1.79). (There
      were no minor allele homozygotes.) In stratified analyses, there was suggestive
      evidence that rs4648319 modified the effect of aspirin. These results support the
      hypothesis that COX-2 plays a role in the etiology of colon cancer and may be a
      target for aspirin chemoprevention and warrant further investigation in other
      colorectal adenoma and cancer populations.

PMID- 19755648
TI  - Folate status and aberrant DNA methylation are associated with HPV infection and
      cervical pathogenesis.
AB  - Aberrant DNA methylation is a recognized feature of human cancers, and folate is
      directly involved in DNA methylation via one-carbon metabolism. Previous reports
      also suggest that folate status is associated with the natural history of human
      papillomavirus (HPV) infection. A cross-sectional study was conducted to test the
      hypothesis that folate status and aberrant DNA methylation show a progressive
      change across stages of cervical pathology from normal cells to cervical cancer.
      Additionally, we postulated that a gene-specific hypermethylation profile might
      be used as a predictive biomarker of cervical cancer risk. DNA hypermethylation
      of seven tumor suppressor genes, global DNA hypomethylation, systemic folate
      status, and HPV status were measured in 308 women with a diagnosis of normal
      cervix (n = 58), low-grade cervical intraepithelial neoplasia (CIN1; n = 68),
      high-grade cervical intraepithelial neoplasia (CIN2, n = 56; and CIN3, n = 76),
      or invasive cervical cancer (ICC; n = 50). Lower folate status was associated
      with high-risk HPV infection (P = 0.031) and with a diagnosis of cervical
      intraepithelial neoplasia or invasive cervical cancer (P < 0.05). Global DNA
      hypomethylation was greater in women with invasive cervical cancer than all other
      groups (P < 0.05). A cluster of three tumor suppressor genes, CDH1, DAPK, and
      HIC1, displayed a significantly increased frequency of promoter methylation with
      progressively more severe cervical neoplasia (P < 0.05). These findings are
      compatible with a role for folate in modulating the risk of cervical cancer,
      possibly through an influence over high-risk HPV infection. DAPK, CDH1, and HIC1
      genes are potential biomarkers of cervical cancer risk.

PMID- 19755649
TI  - Expression and cytoplasmic localization of SAM68 is a significant and independent
      prognostic marker for renal cell carcinoma.
AB  - PURPOSE: This retrospective study aimed to examine the expression and
      localization of SAM68 (Src-associated in mitosis, 68 kDa) in a larger cohort of
      surgical specimens of renal cell carcinoma and their correlation with the
      progression of human renal cell carcinoma. EXPERIMENTAL DESIGN: The protein and
      mRNA expression levels of SAM68 in normal renal tubular epithelial cells, renal
      cell carcinoma cell lines, as well as nine pairs of renal cell carcinoma and
      matched tumor-adjacent renal tissues were examined using reverse transcription
      PCR and Western blot. Moreover, SAM68 protein expression and localization in 241
      clinicopathologically characterized renal cell carcinoma samples were examined by
      immunohistochemistry. Prognostic and diagnostic associations were examined by
      statistical analyses. RESULTS: SAM68 was markedly overexpressed in renal cell
      carcinoma cell lines and renal cell carcinoma tissues at both the transcriptional
      and translational levels. Immunohistochemical analysis revealed high SAM68
      protein expression in 129 of the 241 (53.5%) paraffin-embedded archival renal
      cell carcinoma specimens. Moreover, there was a significant correlation between
      SAM68 expression and pathologic stage (P < 0.001), T classification (P = 0.003),
      N classification (P = 0.001), M classification (P = 0.006), and Fuhrman grade (P
      < 0.001). Patients with higher SAM68 expression had shorter overall survival time
      than patients with lower SAM68 expression, and the cytoplasmic localization of
      SAM68 significantly correlated with clinicopathologic grade and outcome.
      Multivariate analysis indicated that SAM68 protein overexpression and cytoplasmic
      localization were independent predictors for poor survival of renal cell
      carcinoma patients. CONCLUSIONS: Our results suggest that SAM68 could represent a
      novel and useful prognostic marker for renal cell carcinoma. High SAM68
      expression and cytoplasmic localization are associated with poor overall survival
      in renal cell carcinoma patients.

PMID- 19755650
TI  - Occupational exposure to high molecular weight allergens and lymphoma risk among
      Italian adults.
AB  - OBJECTIVES: Exposure to high molecular weight (HMW) allergens that provoke immune
      reactivity through an IgE-mediated pathway has been associated with a decreased
      risk of B-cell lymphoma. The present analysis was conducted to assess the
      associations between occupational exposure to specific HMW allergens and the risk
      of B-cell, T-cell, and Hodgkin's lymphomas. METHODS: We analyzed data from 2,290
      incident lymphoma cases and 1,771 population-based controls enrolled in a
      multicenter study of hematolymphopoietic malignancies conducted in Italy between
      1991 and 1993. All cases were histologically or cytologically confirmed. Controls
      were frequency-matched to cases based on age, sex, and study center. An
      industrial hygienist evaluated HMW occupational exposure classifications after an
      asthma-specific job exposure matrix was applied to participants' job histories.
      Unconditional logistic regression was used to assess associations between
      occupational exposures that occurred > or = 10 years before the date of lymphoma
      diagnosis and B-cell, T-cell, and Hodgkin's lymphomas. RESULTS: Ten percent of
      cases and 11% of controls were occupationally exposed to HMW allergens. Exposed
      individuals had a decreased risk for all lymphomas combined (odds ratio, 0.78;
      95% confidence interval, 0.63-0.97), particularly for B-cell lymphomas (odds
      ratio, 0.75; 95% confidence interval, 0.59-0.94). The decreased risks for all
      lymphomas were also observed when HMW allergen exposure was limited to animal and
      latex allergens. CONCLUSIONS: These findings support the hypothesis that
      occupational exposure to immunologically active HMW allergens is inversely
      associated with the risk for lymphoma. The effect of exposure to specific
      allergens warrants further assessment.

PMID- 19755651
TI  - Prostate cancer detected by methylated gene markers in histopathologically cancer
      negative tissues from men with subsequent positive biopsies.
AB  - The goal of this retrospective, multicenter study was to evaluate the ability of
      a newly developed refinement of a quantitative methylation-specific PCR assay to
      detect prostate cancer in histopathologically negative biopsy samples collected
      from men who were later positively diagnosed during a follow-up biopsy procedure.
      Biomarkers tested in the assay included the much-studied glutathione-S
      transferase P1 gene and others reported to be frequently methylated in prostate
      cancer. Core biopsy tissue from subjects with serial negative biopsies served as
      a negative control to assess assay specificity. As a positive control, biopsy
      core tissue from patients histopathologically diagnosed with prostate cancer was
      used to gauge true marker sensitivity in known cancer-containing specimens.
      Testing was completed in 971 archived paraffin-embedded tissue blocks from 264
      men screened for prostate cancer. More samples were initially tested, but due to
      the advanced age of the paraffinized tissue, DNA quality for quantitative
      methylation-specific PCR analysis was insufficient in 34% of the available
      blocks. The glutathione-S-transferase P1 gene has been confirmed as a powerful
      indicator of the presence of prostate cancer cells. A sensitivity of 52% was
      observed in the "potentially false-negative first biopsies," with a corresponding
      specificity of 85% and the sensitivity in biopsy tissue cores containing
      histopathologically confirmed prostate cancer was 95%. An even higher sensitivity
      can be reached with RAR-2beta (84%) and APC (72%), with respective specificities
      of 48% and 50%. Gene methylation was detected in initial, negative biopsy tissue
      in men who were later diagnosed with prostate cancer. Testing for methylation in
      histopathologically negative biopsies could improve the early detection of
      prostate cancer.

PMID- 19755652
TI  - No risk of maternal EBV infection for childhood leukemia.
AB  - We performed a large nested case-control study within the Finnish and Icelandic
      maternity cohorts to verify/falsify the association of maternal EBV infection
      with an increased risk of acute lymphoblastic leukemia (ALL) in the offspring
      found in previous studies. All hematologic malignancies diagnosed among children
      born during 1983 to 2006 in Finland and 1997 to 2005 in Iceland were identified
      through national cancer registries. For each index mother of a leukemia case,
      three matched control mothers with cancer-free offspring were identified. First
      trimester sera from 561 ALL and 144 non-ALL index mothers and from 2,105 control
      mothers were analyzed for antibodies to EBV viral capsid antigen (IgG and IgM),
      early antigen (IgG) and ZEBRA protein (IgG). Conditional logistic regression
      based estimates of odds ratios and 95% confidence intervals adjusted for birth
      order and sib-ship size were calculated. Overall, there was no evidence of
      increased risk of ALL associated to EBV viral capsid antigen IgM (odds ratio,
      0.9; 95% confidence interval, 0.5-1.8). The early antigen and ZEBRA antibodies
      (EBV reactivation markers) were also not associated with risk. The data argue
      against a role of EBV in ALL.

PMID- 19755653
TI  - Pediatric germ cell tumors and maternal vitamin supplementation: a Children's
      Oncology Group study.
AB  - Maternal vitamin supplementation has been linked to a reduced risk of several
      pediatric malignancies. We examined this relationship in a study of childhood
      germ cell tumors (GCT). Subjects included 278 GCT cases diagnosed <15 years
      during 1993 to 2001 at a United States or Canadian Children's Oncology Group
      Institution and 423 controls that were ascertained through random digit dialing
      matched to cases on sex, and age within 1 year. Unconditional logistic regression
      was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the
      association between GCTs and maternal vitamin use at several time points during
      and around pregnancy. In models controlling for the child's age, sex, household
      income, and maternal education, any maternal vitamin use during the 6 months
      before conception through nursing was associated with a nonsignificant reduced
      risk of GCTs (OR, 0.7; 95% CI, 0.4-1.2). Inverse associations were observed for
      both extragonadal (OR, 0.8; 95% CI, 0.4-1.6) and gonadal (OR, 0.6; 95% CI, 0.3
      1.1) tumors, and for dysgerminoma/seminoma (OR, 0.6; 95% CI, 0.2-1.3) and
      teratoma (OR, 0.5; 95% CI, 0.2-0.9) but not yolk sac tumors (OR, 1.1; 95% CI, 0.5
      2.3). No consistent patterns were found with respect to vitamin use during the
      periconceptional period (6 months before pregnancy and first trimester) or first
      trimester specifically. In conclusion, although our study suggests that maternal
      vitamin supplementation may reduce the risk or pediatric GCTs in the offspring,
      the small study size and limitations inherent to observational studies must be
      considered when interpreting these results.

PMID- 19755654
TI  - The association between skin characteristics and skin cancer prevention
      behaviors.
AB  - BACKGROUND: Behaviors such as sunscreen use and wearing sun-protective clothing
      are thought to prevent certain types of skin cancer and precancerous lesions, but
      few studies have examined differences in these prevention behaviors by skin type.
      METHODS: We carried out a cross-sectional study (n = 6,858) nested within a
      community-based prospective cohort in Washington County, Maryland. We measured
      the associations between skin type, complexion, freckling, and eye color, and
      sunscreen and sun-protective clothing use. RESULTS: The prevalence of regular
      sunscreen use was 23% and regular sun-protective clothing use was 21%. There were
      consistent trends indicating those with the most sun-sensitive skin type were
      most likely to engage in prevention behaviors. For example, compared with those
      who tan without burning, those who develop blistering sunburns were more likely
      to use sunscreen [odds ratio (OR), 6.04; 95% confidence interval (95% CI), 2.82
      12.95 men; OR, 4.89; 95% CI, 3.34-7.16 women] and sun-protective clothing (OR,
      2.87; 95% CI, 1.71-4.80 men; OR, 4.44; 95% CI, 2.88-6.85 women). Health-related
      characteristics such as body mass index and cigarette smoking were also
      significantly inversely associated with prevention behaviors. CONCLUSION: The
      overall prevalence of prevention behaviors was low. Those with phenotypic risk
      factors for skin cancer were most likely to use sunscreen and sun-protective
      clothing. Those with high-risk skin cancer phenotypes may also be those who are
      most receptive to skin cancer prevention educational interventions.

PMID- 19755655
TI  - Serum creatinine and prostate cancer risk in a prospective study.
AB  - BACKGROUND: Several studies have examined serum creatinine as a marker for
      prostate cancer stage, recurrence, and prognosis. We evaluated whether serum
      creatinine concentration was associated with risk of developing prostate cancer
      in a prospective cohort of male smokers. METHODS: A nested case-control study
      within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of 50- to 69
      year-old Finnish men was conducted. Two controls (n = 464) were matched to each
      case (n = 232) on study center, intervention group, date of baseline blood draw
      (+/-45 days), and age (+/-5 years). Conditional logistic regression was used to
      calculate odds ratios and 95% confidence intervals. All P values were two-sided.
      RESULTS: Cases had significantly higher prediagnostic serum creatinine
      concentrations compared with controls (medians of 1.13 versus 1.10 mg/dL,
      respectively; P = 0.004). Serum creatinine was associated with a significantly
      greater risk of prostate cancer (multivariate odds ratio, 2.23; 95% confidence
      interval, 1.33-3.75 for highest versus lowest quartile), with a significant trend
      (P trend = 0.0008). Exclusion of subjects with a reported history of diabetes,
      benign prostatic hyperplasia, or hypertension, or whose cancer was diagnosed
      within the first 5 years of follow-up, did not alter the association. Risk did
      not differ by disease stage or time from blood draw to diagnosis. CONCLUSION:
      Prospectively measured serum creatinine, within normal ranges, is positively
      related to prostate cancer risk. Future research should reexamine the association
      in other populations, including any interrelationship with serum prostate
      specific antigen.

PMID- 19755656
TI  - Nicotinic acetylcholine receptor beta2 subunit (CHRNB2) gene and short-term
      ability to quit smoking in response to nicotine patch.
AB  - Genes coding for nicotinic acetylcholine receptors may influence response to
      nicotine replacement therapy for smoking cessation. We examined the association
      of a 3' untranslated region polymorphism (rs2072661) in the nicotinic
      acetylcholine receptor beta2 subunit (CHRNB2) gene with quitting success in
      response to nicotine versus placebo patch during a short-term test of patch
      effects. In a within-subjects cross-over design, smokers of European descent (n =
      156) received 21 mg nicotine and placebo patch in counter-balanced order, during
      two separate 5-day simulated quit attempts, each preceded by a week of ad libitum
      smoking. Abstinence was assessed daily by CO < 5 ppm. Smokers with the CHRNB2 GG
      genotype had more days of abstinence during the nicotine versus placebo patch
      week compared with those with the AG or AA genotypes (P < 0.01). Moreover,
      nicotine patch increased the probability of quitting on the target quit day,
      quitting anytime during the patch week, and avoiding relapse among those with the
      GG genotype but not the AA/AG genotypes, although the nicotine x genotype
      interaction was significant only for quitting on the target quit day (P < 0.05).
      Regardless of patch condition, quitting on the target quit day was more likely in
      those with the GG genotype versus AA/AG genotypes (P < 0.05). Genetic
      associations were not observed for craving or withdrawal responses to nicotine
      versus placebo patch. These findings are consistent with previous evidence of
      association of this variant with smoking cessation and suggest that polymorphisms
      in the nicotinic acetylcholine receptor beta2 subunit gene may influence
      therapeutic responsiveness to cessation medications.

PMID- 19755657
TI  - Associations between smoking, alcohol consumption, and colorectal cancer, overall
      and by tumor microsatellite instability status.
AB  - INTRODUCTION: Both smoking and alcohol consumption have been associated with
      modestly increased risks of colorectal cancer (CRC). Reports have suggested that
      these associations may differ by tumor molecular subtype, with stronger
      associations for microsatellite unstable (MSI-H) tumors. METHODS: We used a
      population-based case-unaffected sibling design including 2,248 sibships (2,253
      cases; 4,486 siblings) recruited to the Colon Cancer Family Registry to evaluate
      the association between smoking, alcohol consumption, and CRC. Associations were
      assessed using conditional logistic regression, treating sibship as the matching
      factor. RESULTS: Although there were no statistically significant associations
      between any smoking variable and CRC overall, smoking did confer an increased
      risk of certain types of CRC. We observed an association between pack-years of
      smoking and rectal cancer [odds ratio (OR), 1.85; 95% confidence interval (CI),
      1.23-2.79 for >40 pack-years versus nonsmokers; P(trend) = 0.03], and there was
      an increased risk of MSI-H CRC with increasing duration of smoking (OR, 1.94; 95%
      CI, 1.09-3.46 for >30 years of smoking versus nonsmokers). Alcohol intake was
      associated with a modest increase in risk for CRC overall (OR, 1.21; 95% CI, 1.03
      1.44 for 12+ drinks per week versus nondrinkers), with more marked increases in
      risk for MSI-L CRC (OR, 1.85; 95% CI, 1.06-3.24) and rectal cancer (OR, 1.48; 95%
      CI, 1.08-2.02). CONCLUSIONS: We found associations between cigarette smoking and
      increased risks of rectal cancer and MSI-H CRC. Alcohol intake was associated
      with increased risks of rectal cancer and MSI-L CRC. These results highlight the
      importance of considering tumor phenotype in studies of risk factors for CRC.

PMID- 19755658
TI  - The aryl hydrocarbon receptor nuclear translocator (Arnt) is required for tumor
      initiation by benzo[a]pyrene.
AB  - Benzo[a]pyrene (B[a]P) is a ligand for the aryl hydrocarbon receptor (Ahr). After
      binding ligand, Ahr dimerizes with the aryl hydrocarbon receptor nuclear
      translocator (Arnt) protein, and the dimer upregulates the transcription of
      Cyp1a1, Cyp1b1 and other enzymes involved in the metabolic activation of B[a]P.
      Arnt null mice die in utero. Mice in which Arnt deletion occurs constitutively in
      the epidermis die perinatally. In the current study, mice were developed in which
      the Arnt gene could be deleted specifically in adult skin epidermis. This
      deletion had no overt pathological effect. Homozygosity for a null reduced
      nicotinamide adenine dinucleotide (phosphate): quinone oxidoreductase allele was
      introduced into the above mouse strain to render it more susceptible to tumor
      initiation by B[a]P. Deletion of Arnt in the epidermis of this strain completely
      prevented the induction of skin tumors in a tumor initiation-promotion protocol
      in which a single topical application of B[a]P acted as the tumor-initiating
      event, and tumor promotion was provided by repeated topical applications of 12-O
      tetradecanoyl phorbol-13-acetate (TPA). In contrast, deletion of Arnt did not
      prevent the induction of skin tumors in a protocol also using TPA as the promoter
      but using as the initiator N-methyl-N'-nitro-N-nitrosoguanidine, whose activity
      is unlikely to be affected by the activity of Ahr, Arnt or their target genes.
      These observations demonstrate that Arnt is required for tumor initiation by
      B[a]P in this system.

PMID- 19755659
TI  - Sulindac effects on inflammation and tumorigenesis in the intestine of mice with
      Apc and Mlh1 mutations.
AB  - We have previously reported that sulindac, a non-steroidal anti-inflammatory
      drug, inhibited tumor formation in the small intestine but increased tumors in
      the colon of Apc(Min/+) mice, a model of human familial adenomatous polyposis. To
      further explore intestinal regional responses, we studied effects of sulindac on
      additional gene-targeted mouse models of human intestinal tumorigenesis; these
      were (i) Apc(1638N/+) mouse (chain termination mutation in exon 15 of the Apc
      gene); (ii) Mlh1(+/-) mouse (DNA mismatch repair deficiency, a mouse model of
      human hereditary non-polyposis colorectal cancer) and (iii) double-heterozygous
      Mlh1(+/-)Apc(1638N/+) mutant mouse. Mice were fed AIN-76A control diet with or
      without 0.02% sulindac for 6 months. Intestinal regional tumor incidence,
      multiplicity, volume and degree of inflammation were used as end points. The
      results showed the following: (i) sulindac inhibited tumor development in the
      small intestine of Apc(1638N/+) mice; (ii) in contrast, sulindac increased tumors
      in the small intestine of Mlh1 mutant mice, a neoplastic effect which persisted
      in heterozygous compound Mlh1(+/-)Apc(1638N/+) mutant mice; (iii) sulindac
      increased tumors in the cecum of all mice regardless of genetic background; (iv)
      sulindac decreased inflammation in the small intestine of Apc(1638N/+) mice, but
      it increased inflammation in the small intestine of Mlh1(+/-) mice and Mlh1(+/
      )Apc(1638N/+) mice and (v) sulindac enhanced inflammation in the cecum of all
      mutant mice. Findings indicate that the effects of sulindac in the intestine of
      these mutant mouse models are probably related to genetic background and appear
      to be associated with its inflammatory-inducing response.

PMID- 19755660
TI  - Plasma membrane calcium ATPase 4 and the remodeling of calcium homeostasis in
      human colon cancer cells.
AB  - A remodeling of calcium homeostasis has been identified as a characterizing
      feature of some cancers. Possible consequences of this include alterations in
      many pivotal physiological responses including apoptosis, proliferation and gene
      transcription. An alteration in calcium homeostasis can occur via changes in the
      expression of proteins that transport calcium and examples of cancers where this
      is seen includes the prostate and breast. A specific isoform of the calcium
      efflux pump, plasma membrane Ca(2+)-ATPase (PMCA) 4, is significantly upregulated
      during differentiation of the HT-29 colon cancer cell line suggesting that it may
      also be altered in colon cancer. We now report that differentiated HT-29 colon
      cancer cells have pronounced plasma membrane PMCA4 localization, consistent with
      augmented calcium efflux. Assessment of PMCA4 transcription in human colon cancer
      samples suggests that PMCA4 is significantly (P < 0.000001) downregulated early
      in the progression of some colon cancers as these cells become less
      differentiated. Inhibition of PMCA4 using small interfering RNA did not induce
      cell death or augment sensitivity to the mitochondrial uncoupler carbonyl cyanide
      3-chlorophenylhydrazone (CCCP) or tumor necrosis factor-related apoptosis
      inducing ligand. Reversing the colon cancer remodeling of PMCA4 by overexpression
      reduced cellular proliferation (P < 0.01) and downregulated transcription of the
      calcium sensitive early response gene FOS. Our studies suggest that the
      remodeling of the calcium signal in colon cancer is associated with compromised
      calcium efflux at a level that promotes proliferative pathways while avoiding
      increased sensitivity to apoptotic stimuli.

PMID- 19755661
TI  - Activation of the aryl hydrocarbon receptor pathway enhances cancer cell invasion
      by upregulating the MMP expression and is associated with poor prognosis in upper
      urinary tract urothelial cancer.
AB  - Aryl hydrocarbon receptor (AhR) and the activation of the AhR pathway are
      involved in xenobiotic-induced toxicity and carcinogenesis. Although xenobiotics,
      such as cigarette smoke, contribute to the development of urothelial carcinoma
      (UC), the relationship between AhR and UC is unclear. In the present study, we
      investigated AhR expression in 209 patients with upper urinary tract UC. The
      nuclear expression of AhR was significantly associated with histological grade,
      pathological T stage, lymphovascular invasion and lymph node involvement. A
      multivariate Cox analysis revealed that nuclear AhR expression was a significant
      and independent predictor for disease-specific survival (hazard ratio = 2.469, P
      = 0.013). To determine whether the AhR pathway can be activated in the T24 UC
      cell line, we examined the expression of cytochrome P450 (CYP) 1A1 and CYP1B1,
      which are target genes of the AhR pathway, following exposure to 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD), a ligand of AhR. TCDD treatment upregulated
      the expression levels of AhR, CYP1A1 and CYP1B1. TCDD enhanced T24 cell invasion
      associated with the upregulation of matrix metalloproteinase (MMP)-1 and MMP-9.
      Furthermore, targeting AhR messenger RNA (mRNA) expression in T24 cells with
      small interfering RNA (siRNA) downregulated the mRNA expression of AhR, CYP1A1,
      CYP1B1, MMP-1, MMP-2 and MMP-9; furthermore, the cells transfected with siRNA for
      AhR showed decreased invasion activity in comparison with the cells transfected
      with a non-targeting siRNA. Our results therefore suggest that AhR plays a role
      in the invasiveness of UC cells and can serve as a marker for the prognosis of
      upper urinary tract UC.

PMID- 19755662
TI  - In vitro and in vivo evidence for a lack of interaction with dopamine D2
      receptors by the metabotropic glutamate 2/3 receptor agonists 1S,2S,5R,6S-2
      aminobicyclo[3.1.0]hexane-2,6-bicaroxylate monohydrate (LY354740) and (-)-2-oxa-4
      aminobicyclo[3.1.0] Hexane-4,6-dicarboxylic acid (LY379268).
AB  - Some recently published in vitro studies with two metabotropic glutamate 2/3
      receptor (mGluR(2/3)) agonists [(-)-2-oxa-4-aminobicyclo[3.1.0] hexane-4,6
      dicarboxylic acid (LY379268) and 1S,2S,5R,6S-2-aminobicyclo[3.1.0]hexane-2,6
      bicaroxylate monohydrate (LY354740)] suggest that these compounds may also
      directly interact with dopamine (DA) D(2) receptors. The current in vitro and in
      vivo studies were undertaken to further explore this potential interaction with
      D(2) receptors. LY379268 and LY354740 failed to inhibit D(2) binding in both
      native striatal tissue homogenates and cloned receptors at concentrations up to
      10 microM. LY379268 and LY354740 (up to 10 microM) also failed to stimulate
      [(35)S]GTPgammaS binding in D(2L)- and D(2S)-expressing clones in the presence of
      NaCl or N-methyl-d-glucamine. In an in vivo striatal D(2) receptor occupancy
      assay, LY379268 (3-30 mg/kg) or LY354740 (1-10 mg/kg) failed to displace
      raclopride (3 microg/kg i.v.), whereas aripiprazole (10-60 mg/kg) showed up to
      90% striatal D(2) receptor occupancy. LY379268 (10 mg/kg) and raclopride (3
      mg/kg) blocked d-amphetamine and phencyclidine (PCP)-induced hyperactivity in
      wild-type mice. However, the effects of LY379268 were lost in mGlu(2/3) receptor
      knockout mice. In DA D(2) receptor-deficient mice, LY379268 but not raclopride
      blocked both PCP and d-amphetamine-evoked hyperactivity. In the striatum and
      nucleus accumbens, LY379268 (3 and 10 mg/kg) was without effect on the DA
      synthesis rate in reserpinized rats and also failed to prevent S-(-)-3-(3
      hydroxyphenyl)-N-propylpiperidine-induced reductions in DA synthesis rate. Taken
      together, the current data fail to show evidence of direct DA D(2) receptor
      interactions of LY379268 and LY354740 in vitro or in vivo. Instead, these results
      provide further evidence for a novel antipsychotic mechanism of action for
      mGluR(2/3) agonists.

PMID- 19755663
TI  - PPAR-alpha contributes to the anti-inflammatory activity of 17beta-estradiol.
AB  - Because studies have shown that 17beta-estradiol (E2) produces anti-inflammatory
      effects after various adverse circulatory conditions, we have recently
      demonstrated that E2 significantly reduced the acute lung injury. Moreover,
      previous results suggest that peroxisome proliferator-activated receptor-alpha
      (PPAR-alpha), an intracellular transcription factor activated by fatty acids,
      plays a role in the control of inflammation. With the aim to characterize the
      role of PPAR-alpha in estrogen-mediated anti-inflammatory activity, we tested the
      efficacy of E2 in an experimental model of lung inflammation, carrageenan-induced
      pleurisy, comparing ovariectomized wild-type (WT) and PPAR-alpha lacking (PPAR
      alphaKO) mice. Results indicate that E2-mediated anti-inflammatory activity is
      weakened in PPAR-alphaKO mice, compared with WT control groups. In particular, E2
      was less effective in PPAR-alphaKO, compared with WT mice, in inhibition of cell
      migration as well as lung injury, NF-kB activation, TNF-alpha production, and
      inducible nitric-oxide synthase (iNOS) activation. Moreover, macrophages from
      PPAR-alphaKO were less susceptible to E2-induced iNOS inhibition in vitro
      compared with macrophages from WT mice. Moreover, the results indicate that PPAR
      alpha was required for estrogen receptor up-regulation, following E2 treatment.
      These results show for the first time that PPAR-alpha contributes to the anti
      inflammatory activity of E2.

PMID- 19755664
TI  - Transforming "apathy into movement": the role of prosocial emotions in motivating
      action for social change.
AB  - This article explores the synergies between recent developments in the social
      identity of helping, and advantaged groups' prosocial emotion. The authors review
      the literature on the potential of guilt, sympathy, and outrage to transform
      advantaged groups' apathy into positive action. They place this research into a
      novel framework by exploring the ways these emotions shape group processes to
      produce action strategies that emphasize either social cohesion or social change.
      These prosocial emotions have a critical but underrecognized role in creating
      contexts of in-group inclusion or exclusion, shaping normative content and
      meaning, and informing group interests. Furthermore, these distinctions provide a
      useful way of differentiating commonly discussed emotions. The authors conclude
      that the most "effective" emotion will depend on the context of the inequality
      but that outrage seems particularly likely to productively shape group processes
      and social change outcomes.

PMID- 19755665
TI  - Origin and evolution of the unique tetra-domain hemoglobin from the hydrothermal
      vent scale worm Branchipolynoe.
AB  - Hemoglobin is the most common respiratory pigment in annelids. It can be intra or
      extracellular, and this latter type can form large multimeric complexes. The
      hydrothermal vent scale worms Branchipolynoe symmytilida and Branchipolynoe
      seepensis express an extracellular tetra-domain hemoglobin (Hb) that is unique in
      annelids. We sequenced the gene for the single-domain and tetra-domain globins in
      these two species. The single-domain gene codes for a mature protein of 137 amino
      acids, and the tetra-domain gene codes for a mature protein of 552 amino acids.
      The single-domain gene has a typical three exon/two intron structure, with
      introns located at their typical positions (B12.2 and G7.0). This structure is
      repeated four times in the tetra-domain gene, with no bridge introns or linker
      sequences between domains. The phylogenetic position of Branchipolynoe globins
      among known annelid globins revealed that, although extracellular, they cluster
      within the annelid intracellular globins clade, suggesting that the extracellular
      state of these Hbs is the result of convergent evolution. The tetra-domain
      structure likely resulted from two tandem duplications, domain 1 giving rise to
      domain 2 and after this the two-domain gene duplicated to produce domains 3 and
      4. The high O(2) affinity of Branchipolynoe extracellular globins may be
      explained by the two key residues (B10Y and E7Q) in the heme pocket in each of
      the domains of the single and tetra-domain globins, which have been shown to be
      essential in the oxygen-avid Hb from the nematode Ascaris suum. This peculiar
      globin evolutionary path seems to be very different from other annelid
      extracellular globins and is most likely the product of evolutionary tinkering
      associated with the strong selective pressure to adapt to chronic hypoxia that
      characterizes hydrothermal vents.

PMID- 19755666
TI  - Philippine mitochondrial DNA diversity: a populated viaduct between Taiwan and
      Indonesia?
AB  - Relatively little is known about the genetic diversity of the Philippine
      population, and this is an important gap in our understanding of Southeast Asian
      and Oceanic prehistory. Here we describe mitochondrial DNA (mtDNA) variation in
      423 Philippine samples and analyze them in the context of the genetic diversity
      of other Southeast Asian populations. The majority of Philippine mtDNA types are
      shared with Taiwanese aboriginal groups and belong to haplogroups of postglacial
      and pre-Neolithic origin that have previously been identified in East Asian and
      Island Southeast Asian populations. Analysis of hypervariable segment I sequence
      variation within individual mtDNA haplogroups indicates a general decrease in the
      diversity of the most frequent types (B4a1a, E1a1a, and M7c3c) from the Taiwanese
      aborigines to the Philippines and Sulawesi, although calculated standard error
      measures overlap for these populations. This finding, together with the
      geographical distribution of ancestral and derived haplotypes of the B4a1a
      subclade including the Polynesian Motif, is consistent with southward dispersal
      of these lineages "Out of Taiwan" via the Philippines to Near Oceania and
      Polynesia. In addition to the mtDNA components shared with Taiwanese aborigines,
      complete sequence analyses revealed a minority of lineages in the Philippines
      that share their origins--possibly dating back to the Paleolithic--with
      haplogroups from Indonesia and New Guinea. Other rare lineages in the Philippines
      have no closely related types yet identified elsewhere.

PMID- 19755667
TI  - Translational implications of nongenomic actions of thyroid hormone initiated at
      its integrin receptor.
AB  - A thyroid hormone receptor on integrin alphavbeta3 that mediates cell surface
      initiated nongenomic actions of thyroid hormone on tumor cell proliferation and
      on angiogenesis has been described. Transduction of the hormone signal into these
      recently recognized proliferative effects is by extracellular-regulated kinases
      1/2 (ERK1/2). Other nongenomic actions of the hormone may be transduced by
      phosphatidylinositol 3-kinase (PI3K) and are initiated in cytoplasm or at the
      cell surface. PI3K-mediated effects are important to angiogenesis or other
      recently appreciated cell functions but apparently not to tumor cell division.
      For those actions of thyroid hormone [L-thyroxine (T(4)) and 3,3'-5-triiodo-L
      thyronine (T(3))] that begin at the integrin receptor, tetraiodothyroacetic acid
      (tetrac) is an inhibitor of and probe for the participation of the receptor in
      downstream intracellular events. In addition, tetrac has actions initiated at the
      integrin receptor that are unrelated to inhibition of the effects of T(4) and
      T(3) but do involve gene transcription in tumor cells. Discussed here are the
      implications of translating these nongenomic mechanisms of thyroid hormone
      analogs into clinical cancer cell biology, tumor-related angiogenesis, and
      modulation of angiogenesis that is not related to cancer.

PMID- 19755668
TI  - Castration differentially alters basal and leucine-stimulated tissue protein
      synthesis in skeletal muscle and adipose tissue.
AB  - Reduced testosterone as a result of catabolic illness or aging is associated with
      loss of muscle and increased adiposity. We hypothesized that these changes in
      body composition occur because of altered rates of protein synthesis under basal
      and nutrient-stimulated conditions that are tissue specific. The present study
      investigated such mechanisms in castrated male rats (75% reduction in
      testosterone) with demonstrated glucose intolerance. Over 9 wk, castration
      impaired body weight gain, which resulted from a reduced lean body mass and
      preferential sparing of adipose tissue. Castration decreased gastrocnemius
      weight, but this atrophy was not associated with reduced basal muscle protein
      synthesis or differences in plasma IGF-I, insulin, or individual amino acids.
      However, oral leucine failed to normally stimulate muscle protein synthesis in
      castrated rats. In addition, castration-induced atrophy was associated with
      increased 3-methylhistidine excretion and in vitro-determined ubiquitin
      proteasome activity in skeletal muscle, changes that were associated with
      decreased atrogin-1 or MuRF1 mRNA expression. Castration decreased heart and
      kidney weight without reducing protein synthesis and did not alter either cardiac
      output or glomerular filtration. In contradistinction, the weight of the
      retroperitoneal fat depot was increased in castrated rats. This increase was
      associated with an elevated rate of basal protein synthesis, which was
      unresponsive to leucine stimulation. Castration also decreased whole body fat
      oxidation. Castration increased TNFalpha, IL-1alpha, IL-6, and NOS2 mRNA in fat
      but not muscle. In summary, the castration-induced muscle wasting results from an
      increased muscle protein breakdown and the inability of leucine to stimulate
      protein synthesis, whereas the expansion of the retroperitoneal fat depot appears
      mediated in part by an increased basal rate of protein synthesis-associated
      increased inflammatory cytokine expression.

PMID- 19755669
TI  - Sex differences in the regulation of Kiss1/NKB neurons in juvenile mice:
      implications for the timing of puberty.
AB  - In mammals, puberty onset typically occurs earlier in females than in males, but
      the explanation for sexual differentiation in the tempo of pubertal development
      is unknown. Puberty in both sexes is a brain-dependent phenomenon and involves
      alterations in the sensitivity of neuronal circuits to gonadal steroid feedback
      as well as gonadal hormone-independent changes in neuronal circuitry. Kisspeptin,
      encoded by the Kiss1 gene, plays an essential but ill-defined role in pubertal
      maturation. Neurokinin B (NKB) is coexpressed with Kiss1 in the arcuate nucleus
      (ARC) and is also important for puberty. We tested whether sex differences in the
      timing of pubertal development are attributable to sexual differentiation of
      gonadal hormone-independent mechanisms regulating hypothalamic Kiss1/NKB gene
      expression. We found that, in juvenile females, gonadotropin secretion and
      expression of Kiss1 and NKB in the ARC increased immediately following
      ovariectomy, suggesting that prepubertal females have negligible gonadal hormone
      independent restraint on their reproductive axis. In contrast, in similarly aged
      juvenile males, no changes occurred in LH levels or Kiss1 or NKB expression
      following castration, suggesting that gonadal hormone-independent mechanisms
      restrain kisspeptin/NKB-dependent activation of the male reproductive axis before
      puberty. Notably, adult mice of both sexes showed comparable rapid increases in
      Kiss1/NKB expression and LH secretion following gonadectomy, signifying that sex
      differences in the regulation of ARC Kiss1/NKB neurons are manifest only during
      peripubertal development. Our findings demonstrate that the mechanisms
      controlling pubertal activation of reproduction in mice are different between the
      sexes and suggest that gonadal hormone-independent central restraint on pubertal
      timing involves Kiss1/NKB neurons in the ARC.

PMID- 19755670
TI  - The effect of high-dose sodium salicylate on chronically elevated plasma
      nonesterified fatty acid-induced insulin resistance and beta-cell dysfunction in
      overweight and obese nondiabetic men.
AB  - Prolonged elevation of plasma nonesterified fatty acids (NEFA) induces insulin
      resistance and impairs pancreatic beta-cell adaptation to insulin resistance.
      Studies in rodents suggest that inflammation may play a role in this
      "lipotoxicity." We studied the effects of sodium salicylate, an anti-inflammatory
      agent, on lipid-induced alterations in beta-cell function and insulin sensitivity
      in six overweight and obese nondiabetic men. Each subject underwent four separate
      studies, 4-6 wk apart, in random order: 1) SAL, 1-wk placebo followed by
      intravenous (iv) infusion of saline for 48 h; 2) IH, 1-wk placebo followed by iv
      infusion of intralipid plus heparin for 48 h to raise plasma NEFA approximately
      twofold; 3) IH + SS, 1-wk sodium salicylate (4.5 g/day) followed by 48-h IH
      infusion; and 4) SS, 1-wk oral sodium salicylate followed by 48-h saline
      infusion. After 48-h saline or lipid infusion, insulin secretion and sensitivity
      were assessed by hyperglycemic clamp and euglycemic hyperinsulinemic clamp,
      respectively, in sequential order. Insulin sensitivity was reduced by lipid
      infusion (IH = 67% of SAL) and was not improved by salicylate (IH + SS = 56% of
      SAL). Lipid infusion also reduced the disposition index (P < 0.05), which was not
      prevented by sodium salicylate. Salicylate reduced insulin clearance. These data
      suggest that oral sodium salicylate at this dose impairs insulin clearance but
      does not ameliorate lipid-induced insulin resistance and beta-cell dysfunction in
      overweight and obese nondiabetic men.

PMID- 19755671
TI  - Different impacts of saturated and unsaturated free fatty acids on COX-2
      expression in C(2)C(12) myotubes.
AB  - In skeletal muscle, saturated free fatty acids (FFAs) act as proinflammatory
      stimuli, and cyclooxygenase-2 (COX-2) is a pro/anti-inflammatory enzyme induced
      at sites of inflammation, which contributes to prostaglandin production. However,
      little is known about the regulation of COX-2 expression and its responses to
      FFAs in skeletal muscle. Herein, we examined the effects of saturated and
      unsaturated FFAs, including a recently identified lipokine (lipid hormone derived
      from adipocytes), palmitoleate, on COX-2 expression in C(2)C(12) myotubes as a
      skeletal muscle model. Exposure of myotubes to saturated FFAs [palmitate (16:0)
      and stearate (18:0)], but not to unsaturated FFAs [palmitoleate (16:1), oleate
      (18:1), and linoleate (18:2)], led to a slow-onset induction of COX-2 expression
      and subsequent prostaglandin E(2) production via mechanisms involving the p38
      MAPK and NF-kappaB but not the PKC signaling cascades. Pharmacological modulation
      of mitochondrial oxidative function failed to interfere with COX-2 expression,
      suggesting the mitochondrial overload/excessive beta-oxidation contribution to
      this event to be minimal. On the contrary, unsaturated FFAs appeared to
      effectively antagonize palmitate-induced COX-2 expression with markedly different
      potencies (linoleate > oleate > palmitoleate), being highly associated with the
      suppressive profile of each unsaturated FFA toward palmitate-evoked intracellular
      signals, including p38, JNK, ERK1/2 MAPKs, and PKCtheta, as well as IkappaB
      degradation. In addition, our data suggest little involvement of PPAR in the
      protective actions of unsaturated FFAs against palmitate-induced COX-2
      expression. No direct contribution of the increased COX-2 activity in generating
      palmitate-induced insulin resistance was detected, at least in terms of insulin
      responsive Akt phosphorylation and GLUT4 translocation. Taken together, our data
      provide a novel insight into the molecular mechanisms responsible for the FFA
      induced COX-2 expression in skeletal muscle and raise the possibility that, in
      skeletal myocytes, COX-2 and its product prostaglandins may play an important
      role in the complex inflammation responses caused by elevated FFAs, for example,
      in the diabetic state.

PMID- 19755672
TI  - Deletion of Fas in the pancreatic beta-cells leads to enhanced insulin secretion.
AB  - Fas/Fas ligand belongs to the tumor necrosis factor superfamily of
      receptors/ligands and is best known for its role in apoptosis. However, recent
      evidence supports its role in other cellular responses, including proliferation
      and survival. Although Fas has been implicated as an essential mediator of beta
      cell death in the pathogenesis of type 1 diabetes, the essential role of Fas
      specifically in pancreatic beta-cells has been found to be controversial.
      Moreover, the role of Fas on beta-cell homeostasis and function is not clear. The
      objective of this study is to determine the role of Fas specifically in beta
      cells under both physiological and diabetes models. Mice with Fas deletion
      specifically in the beta-cells were generated using the Cre-loxP system. Cre
      mediated Fas deletion was under the control of the rat insulin promoter. Absence
      of Fas in beta-cells leads to complete protection against FasL-induced cell
      death. However, Fas is not essential in determining beta-cell mass or
      susceptibility to streptozotocin- or HFD-induced diabetes. Importantly, Fas
      deletion in beta-cells leads to increased p65 expression, enhanced glucose
      tolerance, and glucose-stimulated insulin secretion, with increased exocytosis as
      manifested by increased changes in membrane capacitance and increased expression
      of Syntaxin1A, VAMP2, and munc18a. Together, our study shows that Fas in the beta
      cells indeed plays an essential role in the canonical death receptor-mediated
      apoptosis but is not essential in regulating beta-cell mass or diabetes
      development. However, beta-cell Fas is critical in the regulation of glucose
      homeostasis through regulation of the exocytosis machinery.

PMID- 19755673
TI  - Chronic lymphocytic leukemia of Emu-TCL1 transgenic mice undergoes rapid cell
      turnover that can be offset by extrinsic CD257 to accelerate disease progression.
AB  - Results of heavy-water labeling studies have challenged the notion that chronic
      lymphocytic leukemia (CLL) represents an accumulation of noncycling B cells. We
      examined leukemia cell turnover in Emu-TCL1 transgenic (TCL1-Tg) mice, which
      develop a CLL-like disease at 8 to 12 months of age. We found that leukemia cells
      in these mice not only had higher proportions of proliferating cells but also
      apoptotic cells than did nonleukemic lymphocytes. We crossed TCL1-Tg with BAFF-Tg
      mice, which express high levels of CD257. TCL1 x BAFF-Tg mice developed CLL-like
      disease at a significantly younger age and had more rapid disease progression and
      shorter survival than TCL1-Tg mice. Leukemia cells of TCL1 x BAFF-Tg mice had
      similar proportions of proliferating cells, but fewer proportions of dying cells,
      than did the CLL cells of TCL1-Tg mice. Moreover, leukemia cells from either TCL1
      x BAFF-Tg or TCL1-Tg mice produced more aggressive disease when transferred into
      BAFF-Tg mice than into wild-type (WT) mice. Neutralization of CD257 resulted in
      rapid reduction in circulating leukemia cells. These results indicate that the
      leukemia cells of TCL1-Tg mice undergo high levels of spontaneous apoptosis that
      is offset by relatively high rates of leukemia cell proliferation, which might
      allow for acquisition of mutations that contribute to disease evolution.

PMID- 19755675
TI  - Gene expression-based classification and regulatory networks of pediatric acute
      lymphoblastic leukemia.
AB  - Pediatric acute lymphoblastic leukemia (ALL) contains cytogenetically distinct
      subtypes that respond differently to cytotoxic drugs. Subtype classification can
      be also achieved through gene expression profiling. However, how to apply such
      classifiers to a single patient and correctly diagnose the disease subtype in an
      independent patient group has not been addressed. Furthermore, the underlying
      regulatory mechanisms responsible for the subtype-specific gene expression
      patterns are still largely unknown. Here, by combining 3 published microarray
      datasets on 535 mostly white children's samples and generating a new dataset on
      100 Chinese children's ALL samples, we were able to (1) identify a 62-gene
      classifier with 97.6% accuracy from the white children's samples and validated it
      on the completely independent set of 100 Chinese samples, and (2) uncover
      potential regulatory networks of ALL subtypes. The classifier we identified was,
      thus far, the only one that could be applied directly to a single sample and that
      sustained validation in a large independent patient group. Our results also
      suggest that the etiology of ALL is largely the same among different ethnic
      groups, and that the transcription factor hubs in the predicted regulatory
      network might play important roles in regulating gene expression and development
      of ALL.

PMID- 19755674
TI  - The persistence of immunophenotypically normal residual bone marrow plasma cells
      at diagnosis identifies a good prognostic subgroup of symptomatic multiple
      myeloma patients.
AB  - Multiparameter flow cytometry immunophenotyping allows discrimination between
      normal (N-) and myelomatous (MM-) plasma cells (PCs) within the bone marrow
      plasma cell compartment (BMPCs). Here we report on the prognostic relevance of
      detecting more than 5% residual normal plasma cells from all bone marrow plasma
      cells (N-PCs/BMPCs) by multiparameter flow cytometry in a series of 594 newly
      diagnosed symptomatic MM patients, uniformly treated according to the Grupo
      Espanol de MM 2000 (GEM2000) protocol. Our results show that symptomatic MM
      patients with more than 5% N-PCs/BMPCs (n = 80 of 594; 14%) have a favorable
      baseline clinical prospect, together with a significantly lower frequency of high
      risk cytogenetic abnormalities and higher response rates. Moreover, this group of
      patients had a significantly longer progression-free survival (median, 54 vs 42
      months, P = .001) and overall survival (median, not reached vs 89 months, P =
      .04) than patients with less than or equal to 5% N-PCs/BMPCs. Our findings
      support the clinical value of detecting residual normal PCs in MM patients at
      diagnosis because this reveals a good prognostic category that could benefit from
      specific therapeutic approaches. This trial was registered at
      www.clinicaltrials.gov as NCT00560053.

PMID- 19755676
TI  - TC-PTP is required for the maintenance of MYC-driven B-cell lymphomas.
AB  - We sought to determine the contributions of protein tyrosine phosphatases (PTPs)
      to the pathogenesis of B-cell lymphomas. We found that T-cell PTP (TC-PTP) was
      overexpressed in transformed B cells. We hypothesized that TC-PTP may be a tumor
      promoting gene that is regulated by MYC overexpression in B cells. Knockdown of
      TC-PTP in murine tumors resulted in decreased cell viability in vitro because of
      an arrest in the G(1) phase of the cell cycle. Furthermore, cells with reduced TC
      PTP expression were unable to either engraft or expand in vivo. Taken together,
      these data indicate that TC-PTP is required for B-cell tumor maintenance. Our
      data also suggested a correlation between TC-PTP expression and MYC
      overexpression. To investigate this further, we used malignant murine B cells
      that contain a doxycycline-repressible MYC transgene. We found that repression of
      MYC overexpression with doxycycline reduced TC-PTP expression. Moreover, enforced
      expression of TC-PTP showed partial rescue of the expansion of tumor cells after
      suppression of MYC overexpression. These results suggest that MYC overexpression
      induces TC-PTP overexpression, which in turn promotes tumor proliferation,
      implicating TC-PTP as an important effector of the MYC-driven proliferation
      program in B-cell lymphomas. Thus, TC-PTP may be a suitable molecular target for
      the treatment of B-cell lymphomas.

PMID- 19755677
TI  - Epigenetic therapies move into new territory, but how exactly do they work?

PMID- 19755678
TI  - StatBite: Breast cancer: 5-year survival rates in U.S. for selected histologic
      types by stage.

PMID- 19755679
TI  - Gastric cancer: trastuzumab trial results spur search for other targets.

PMID- 19755680
TI  - Drugs are scarce as mix of programs aims to ease access.

PMID- 19755681
TI  - Inflammatory breast cancer: new hopes and many hurdles.

PMID- 19755685
TI  - The cover. Lute-player.

PMID- 19755686
TI  - A piece of my mind. Driving thoughts.

PMID- 19755687
TI  - CDC names H1N1 vaccine priority groups.

PMID- 19755688
TI  - Report offers clinicians guidance for treating depression during pregnancy.

PMID- 19755689
TI  - Studies probe US traffic injuries, deaths: focus on factors that reduce,
      exacerbate toll.

PMID- 19755690
TI  - Aspirin for prevention of stroke and cardiovascular events among patients with
      peripheral artery disease.

PMID- 19755691
TI  - Assessing cardiovascular risk factors in National Football League players.

PMID- 19755692
TI  - Depression in at-risk adolescents and their parents.

PMID- 19755693
TI  - Substance abuse and violent crime in patients with schizophrenia.

PMID- 19755694
TI  - Tort claims and federal regulation of medical devices vs pharmaceuticals.

PMID- 19755695
TI  - Small-intestinal histopathology and mortality risk in celiac disease.
AB  - CONTEXT: Studies of mortality in celiac disease have not taken small-intestinal
      pathology into account. OBJECTIVE: To examine mortality in celiac disease
      according to small-intestinal histopathology. DESIGN, SETTING, AND PATIENTS:
      Retrospective cohort study. We collected data from duodenal/jejunal biopsies
      taken between July 1969 and February 2008 on celiac disease (Marsh stage 3:
      villous atrophy; n = 29,096 individuals) and inflammation (Marsh stage 1-2; n =
      13,306) from all 28 pathology departments in Sweden. A third cohort consisted of
      individuals with latent celiac disease from 8 university hospitals (n = 3719).
      Latent celiac disease was defined as positive celiac disease serology in
      individuals with normal mucosa (Marsh stage 0). Through linkage with the Swedish
      Total Population Register, we estimated the risk of death through August 31,
      2008, compared with age- and sex-matched controls from the general population.
      MAIN OUTCOME MEASURE: All-cause mortality. RESULTS: There were 3049 deaths among
      patients with celiac disease, 2967 with inflammation, and 183 with latent celiac
      disease. We found an increased hazard ratio (HR) for death in celiac disease (HR,
      1.39; 95% confidence interval [CI], 1.33-1.45; median follow-up, 8.8 years),
      inflammation (HR, 1.72; 95% CI, 1.64-1.79; median follow-up, 7.2 years), and
      latent celiac disease (HR, 1.35; 95% CI, 1.14-1.58; median follow-up, 6.7 years).
      The absolute mortality rate was 10.4 (95% CI, 10.0-10.8) per 1000 person-years in
      celiac disease, 25.9 (95% CI, 25.0-26.8) in inflammation, and 6.7 (95% CI, 5.7
      7.6) in latent celiac disease. Excess mortality was 2.9 per 1000 person-years in
      celiac disease, 10.8 in inflammation, and 1.7 in latent celiac disease. This risk
      increase was also seen in children. Excluding the first year of follow-up, HRs
      decreased somewhat. CONCLUSION: Risk of death among patients with celiac disease,
      inflammation, or latent celiac disease is modestly increased.

PMID- 19755696
TI  - Chronic dialysis and death among survivors of acute kidney injury requiring
      dialysis.
AB  - CONTEXT: Severe acute kidney injury among hospitalized patients often
      necessitates initiation of short-term dialysis. Little is known about the long
      term outcome of those who survive to hospital discharge. OBJECTIVE: To assess the
      risk of chronic dialysis and all-cause mortality in individuals who experience an
      episode of acute kidney injury requiring dialysis. DESIGN, SETTING, AND
      PARTICIPANTS: We conducted a population-based cohort study of all adult patients
      in Ontario, Canada, with acute kidney injury who required in-hospital dialysis
      and survived free of dialysis for at least 30 days after discharge between July
      1, 1996, and December 31, 2006. These individuals were matched with patients
      without acute kidney injury or dialysis during their index hospitalization.
      Matching was by age plus or minus 5 years, sex, history of chronic kidney
      disease, receipt of mechanical ventilation during the index hospitalization, and
      a propensity score for developing acute kidney injury requiring dialysis.
      Patients were followed up until March 31, 2007. MAIN OUTCOME MEASURES: The
      primary end point was the need for chronic dialysis and the secondary outcome was
      all-cause mortality. RESULTS: We identified 3769 adults with acute kidney injury
      requiring in-hospital dialysis and 13 598 matched controls. The mean age was 62
      years and median follow-up was 3 years. The incidence rate of chronic dialysis
      was 2.63 per 100 person-years among individuals with acute kidney injury
      requiring dialysis, and 0.91 per 100 person-years among control participants
      (adjusted hazard ratio, 3.23; 95% confidence interval, 2.70-3.86). All-cause
      mortality rates were 10.10 and 10.85 per 100 person-years, respectively (adjusted
      hazard ratio, 0.95; 95% confidence interval, 0.89-1.02). CONCLUSIONS: Acute
      kidney injury necessitating in-hospital dialysis was associated with an increased
      risk of chronic dialysis but not all-cause mortality.

PMID- 19755697
TI  - Effects of initiating insulin and metformin on glycemic control and inflammatory
      biomarkers among patients with type 2 diabetes: the LANCET randomized trial.
AB  - CONTEXT: As diabetes is in part an inflammatory condition, the initiation of
      insulin and/or metformin may beneficially reduce levels of inflammatory
      biomarkers such as high-sensitivity C-reactive protein (hsCRP). OBJECTIVE: To
      determine whether insulin alone or combined with metformin lowers levels of
      hsCRP, IL-6, and soluble tumor necrosis factor receptor 2 (sTNFr2) in patients
      with recent-onset type 2 diabetes mellitus. DESIGN, SETTING, AND PARTICIPANTS:
      Randomized 2 x 2 factorial trial of open-label insulin glargine and placebo
      controlled metformin in 500 adults with type 2 diabetes (median time from
      diagnosis, 2.0 years), suboptimal glycemic control, and elevated hsCRP levels.
      Patients were recruited from US office-based practices between October 2006 and
      December 2008. INTERVENTION: Random allocation to 1 of 4 treatments (placebo
      metformin only, placebo metformin and insulin glargine, active metformin only, or
      active metformin and insulin glargine) with dose titration targeting fasting
      blood glucose less than 110 mg/dL. MAIN OUTCOME MEASURES: Change in hsCRP level
      (primary end point) and change in IL-6 and sTNFr2 levels (secondary end points)
      from baseline to 14 weeks. RESULTS: Levels of glucose and glycated hemoglobin
      (HbA(1c)) were significantly reduced with active treatment vs placebo (all P
      values <.001). Levels of hsCRP were reduced in all 4 groups. There was no
      significant difference in hsCRP reduction among those allocated to insulin (
      11.8%; 95% CI, -18.7% to -4.4%) or to no insulin (-17.5%; 95% CI, -23.9% to 
      10.5%) (P for difference = .25), or among those allocated to active metformin (
      18.1%; 95% CI, -24.4% to -11.1%) or placebo metformin (-11.2%; 95% CI, -18.1% to 
      3.7%) (P for difference = .17). In the individual treatment groups, despite a
      differential impact on glucose control, reductions in hsCRP in the metformin (
      16.1%; 95% CI, -25.1% to -6.1%) and metformin plus insulin (-20.1%; 95% CI, 
      28.8% to -10.4%) groups were no different than reductions with placebo alone (
      19.0%; 95% CI, -27.8% to -9.1%; P = .67 and .87 vs placebo, respectively). By
      contrast, hsCRP reduction was attenuated with insulin alone (-2.9%, 95% CI, 
      13.2% to 8.6%; P = .03 vs placebo). Similar findings were noted for levels of IL
      6 and sTNFr2. CONCLUSION: In patients with recent-onset type 2 diabetes,
      treatment with insulin or metformin compared with placebo did not reduce
      inflammatory biomarker levels despite improving glucose control. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT00366301.

PMID- 19755698
TI  - Racial differences in survival after in-hospital cardiac arrest.
AB  - CONTEXT: Racial differences in survival have not been previously studied after in
      hospital cardiac arrest, an event for which access to care is not likely to
      influence treatment. OBJECTIVES: To estimate racial differences in survival for
      patients with in-hospital cardiac arrests and examine the association of
      sociodemographic and clinical factors and the admitting hospital with racial
      differences in survival. DESIGN, SETTING, AND PATIENTS: Cohort study of 10,011
      patients with cardiac arrests due to ventricular fibrillation or pulseless
      ventricular tachycardia enrolled between January 1, 2000, and February 29, 2008,
      at 274 hospitals within the National Registry of Cardiopulmonary Resuscitation.
      MAIN OUTCOME MEASURES: Survival to hospital discharge; successful resuscitation
      from initial arrest and postresuscitation survival (secondary outcome measures).
      RESULTS: Included were 1883 black patients (18.8%) and 8128 white patients
      (81.2%). Rates of survival to discharge were lower for black patients (25.2%)
      than for white patients (37.4%) (unadjusted relative rate [RR], 0.73; 95%
      confidence interval [CI], 0.67-0.79). Unadjusted racial differences narrowed
      after adjusting for patient characteristics (adjusted RR, 0.81 [95% CI, 0.75
      0.88]; P < .001) and diminished further after additional adjustment for hospital
      site (adjusted RR, 0.89 [95% CI, 0.82-0.96]; P = .002). Lower rates of survival
      to discharge for blacks reflected lower rates of both successful resuscitation
      (55.8% vs 67.4% for whites; unadjusted RR, 0.84 [95% CI, 0.81-0.88]) and
      postresuscitation survival (45.2% vs 55.5% for whites; unadjusted RR, 0.85 [95%
      CI, 0.79-0.91]). Adjustment for the hospital site at which patients received care
      explained a substantial portion of the racial differences in successful
      resuscitation (adjusted RR, 0.92 [95% CI, 0.88-0.96]; P < .001) and eliminated
      the racial differences in postresuscitation survival (adjusted RR, 0.99 [95% CI,
      0.92-1.06]; P = .68). CONCLUSIONS: Black patients with in-hospital cardiac arrest
      were significantly less likely to survive to discharge than white patients, with
      lower rates of survival during both the immediate resuscitation and
      postresuscitation periods. Much of the racial difference was associated with the
      hospital center in which black patients received care.

PMID- 19755699
TI  - Outcomes of localized prostate cancer following conservative management.
AB  - CONTEXT: Most newly diagnosed prostate cancers are clinically localized, and
      major treatment options include surgery, radiation, or conservative management.
      Although conservative management can be a reasonable choice, there is little
      contemporary prostate-specific antigen (PSA)-era data on outcomes with this
      approach. OBJECTIVE: To evaluate the outcomes of clinically localized prostate
      cancer managed without initial attempted curative therapy in the PSA era. DESIGN,
      SETTING, AND PARTICIPANTS: A population-based cohort study of men aged 65 years
      or older when they were diagnosed (1992-2002) with stage T1 or T2 prostate cancer
      and whose cases were managed without surgery or radiation for 6 months after
      diagnosis. Living in areas covered by the Surveillance, Epidemiology, and End
      Results (SEER) program, the men were followed up for a median of 8.3 years
      (through December 31, 2007). Competing risk analyses were performed to assess
      outcomes. MAIN OUTCOME MEASURES: Ten-year overall survival, cancer-specific
      survival, and major cancer related interventions. RESULTS: Among men who were a
      median age of 78 years at cancer diagnosis, 10-year prostate cancer-specific
      mortality was 8.3% (95% confidence interval [CI], 4.2%-12.8%) for men with well
      differentiated tumors; 9.1% (95% CI, 8.3%-10.1%) for those with moderately
      differentiated tumors, and 25.6% (95% CI, 23.7%-28.3%) for those with poorly
      differentiated tumors. The corresponding 10-year risks of dying of competing
      causes were 59.8% (95% CI, 53.2%-67.8%), 57.2% (95% CI, 52.6%-63.9%), and 56.5%
      (95% CI, 53.6%-58.8%), respectively. Ten-year disease-specific mortality for men
      aged 66 to 74 years diagnosed with moderately differentiated disease was 60% to
      74% lower than earlier studies: 6% (95% CI, 4%-8%) in the contemporary PSA era
      (1992-2002) compared with results of previous studies (15%-23%) in earlier eras
      (1949-1992). Improved survival was also observed in poorly differentiated
      disease. The use of chemotherapy (1.6%) or major interventions for spinal cord
      compression (0.9%) was uncommon. CONCLUSIONS: Results following conservative
      management of clinically localized prostate cancer diagnosed from 1992 through
      2002 are better than outcomes among patients diagnosed in the 1970s and 1980s.
      This may be due, in part, to additional lead time, overdiagnosis related to PSA
      testing, grade migration, or advances in medical care.

PMID- 19755700
TI  - Vascular abnormalities, paraoxonase activity, and dysfunctional HDL in primary
      antiphospholipid syndrome.
AB  - CONTEXT: Accelerated atherosclerosis has been described in antiphospholipid
      syndrome, but the vascular abnormalities and the underlying mechanisms remain
      unclear. OBJECTIVES: To compare vascular structure and function in patients with
      positive antiphospholipid antibodies (aPL) with controls and to assess their
      relationship with paraoxonase activity. DESIGN, SETTING, AND PARTICIPANTS: A
      cross-sectional study of 77 women with positive antiphospholipid antibodies from
      a lupus outpatient clinic in London, England (90% of the eligible population) and
      77 controls matched on frequency basis for age and cardiovascular risk factors
      between June 2006 and April 2009. Carotid intima media thickness (CIMT), flow
      mediated dilatation, pulse wave velocity, and paraoxonase activity were measured
      in all patients. Anti-inflammatory and antioxidant properties of high-density
      lipoprotein (HDL) were examined. MAIN OUTCOME MEASURES: CIMT, pulse wave
      velocity, flow-mediated dilatation, and paraoxonase. RESULTS: Women with aPL had
      greater CIMT and pulse wave velocity compared with controls (mean [SD], 0.75
      [0.16] vs 0.64 [0.09] mm; 95% confidence interval [CI], -0.14 to -0.06; P < .001;
      and 9.2 [1.6] vs 8.5 [1.8] m/s; 95% CI, -1.14 to -0.06; P = .04) and lower flow
      mediated dilatation (6.2% [4.1%] vs 9.6% [4.2%]; 95% CI, 2.02%-4.69%; P < .001).
      Paraoxonase activity was lower in women with aPL vs controls (median
      [interquartile range], 91.2 [64.3-105.1] vs 103.0 [80.5-111.5] micromol p
      nitrophenol/L/serum/min; 95% CI, 0.004-0.007; P = .005) and was inversely
      associated with CIMT and pulse wave velocity in women with aPL (standardized beta
      coefficient = -0.4 and -0.3, respectively; P < .05 for both), but not in the
      control group. High-density lipoprotein from women with aPL inhibited endothelial
      nitric oxide production in human aortic endothelial cells, in contrast with
      controls. The beneficial effects of HDL from women with aPL on vascular cell
      adhesion molecule 1 expression, superoxide production, and monocyte adhesion
      following activation of human aortic endothelial cells were largely blunted.
      CONCLUSIONS: Compared with controls, women with aPL had greater functional and
      structural arterial abnormalities, which were associated with lower activity of
      paraoxonase. In patients with aPL, HDL reduced nitric oxide bioavailability and
      had impaired anti-inflammatory and antioxidant properties.

PMID- 19755701
TI  - The international response to climate change: an agenda for global health.

PMID- 19755702
TI  - What Mexico taught the world about pandemic influenza preparedness and community
      mitigation strategies.

PMID- 19755703
TI  - Bending the cost curve: a critical component of health care reform.

PMID- 19755704
TI  - Mortality in celiac disease, intestinal inflammation, and gluten sensitivity.

PMID- 19755705
TI  - Chronic on acute renal failure: long-term implications of severe acute kidney
      injury.

PMID- 19755706
TI  - JAMA patient page, Celiac disease.

PMID- 19755707
TI  - Regulation of cancer invasion by reactive oxygen species and Tks family scaffold
      proteins.
AB  - Reactive oxygen species (ROS) are increasingly recognized as important signaling
      regulators. The family of the reduced form of nicotinamide adenine dinucleotide
      phosphate (NADPH) oxidases (Nox's) is responsible for the production of most
      signaling ROS in cells. An emerging paradigm is that individual Nox family
      members are organized and activated at distinct subcellular locations for
      specific functions. Tyrosine kinase substrate (Tks) family adaptor proteins have
      now been identified as Nox organizer proteins that enhance the production of ROS
      at invadopodia and podosomes, which are subcellular adhesion structures
      associated with extracellular matrix degradation. ROS production is also shown to
      be required for invadopodia and podosome formation. These findings broaden the
      known signaling roles of ROS and identify a potential mechanism for the
      correlation of ROS production with cancer invasion.

PMID- 19755708
TI  - Endocannabinoids can open the pain gate.
AB  - Endocannabinoids produced in the spinal cord can enhance pain by dampening the
      synapses of inhibitory interneurons that usually prevent the perception of
      innocuous stimuli as painful. This mechanism promotes pain responsiveness to
      normally innocuous mechanical stimuli in the skin surrounding a site of injury in
      both animals and humans subjected to sustained stimulation of pain-sensing
      nerves. The pain-promoting action of endocannabinoids wanes during the
      development of chronic pain that is induced by inflammation or nerve injury. This
      finding may partially explain why, in human trials, cannabinoid drugs have been
      negative for treatment of most types of acute and postsurgical pain but are
      effective for some chronic pain states.

PMID- 19755709
TI  - Tks5-dependent, nox-mediated generation of reactive oxygen species is necessary
      for invadopodia formation.
AB  - Invadopodia are actin-rich membrane protrusions of cancer cells that facilitate
      pericellular proteolysis and invasive behavior. We show here that reactive oxygen
      species (ROS) generated by the NADPH (reduced form of nicotinamide adenine
      dinucleotide phosphate) oxidase (Nox) system are necessary for invadopodia
      formation and function. Knockdown of the invadopodia protein Tks5 [tyrosine
      kinase substrate with five Src homology 3 (SH3) domains], which is structurally
      related to the Nox component p47(phox), reduces total ROS abundance in cancer
      cells. Furthermore, Tks5 and p22(phox) can associate with each other, suggesting
      that Tks5 is part of the Nox complex. Tyrosine phosphorylation of Tks5 and Tks4,
      but not other Src substrates, is reduced by Nox inhibition. We propose that Tks5
      facilitates the production of ROS necessary for invadopodia formation, and that
      in turn ROS modulate Tks5 tyrosine phosphorylation in a positive feedback loop.

PMID- 19755710
TI  - Novel p47(phox)-related organizers regulate localized NADPH oxidase 1 (Nox1)
      activity.
AB  - The mechanisms that determine localized formation of reactive oxygen species
      (ROS) through NADPH (reduced form of nicotinamide adenine dinucleotide phosphate)
      oxidase (Nox) family members in nonphagocytic cells are unknown. We show that the
      c-Src substrate proteins Tks4 (tyrosine kinase substrate with four SH3 domains)
      and Tks5 are functional members of a p47(phox)-related organizer superfamily. Tks
      proteins selectively support Nox1 and Nox3 (and not Nox2 and Nox4) activity in
      reconstituted cellular systems and interact with the NoxA1 activator protein
      through an Src homology 3 domain-mediated interaction. Endogenous Tks4 is
      required for Rac guanosine triphosphatase- and Nox1-dependent ROS production by
      DLD1 colon cancer cells. Our results are consistent with the Tks-mediated
      recruitment of Nox1 to invadopodia that form in DLD1 cells in a Tks- and Nox
      dependent fashion. We propose that Tks organizers represent previously
      unrecognized members of an organizer superfamily that link Nox to localized ROS
      formation.

PMID- 19755711
TI  - Differential interactions of FGFs with heparan sulfate control gradient formation
      and branching morphogenesis.
AB  - The developmental activities of morphogens depend on the gradients that they form
      in the extracellular matrix. Here, we show that differences in the binding of
      fibroblast growth factor 7 (FGF7) and FGF10 to heparan sulfate (HS) underlie the
      formation of different gradients that dictate distinct activities during
      branching morphogenesis. Reducing the binding affinity of FGF10 for HS by
      mutating a single residue in its HS-binding pocket converted FGF10 into a
      functional mimic of FGF7 with respect to gradient formation and regulation of
      branching morphogenesis. In particular, the mutant form of FGF10 caused lacrimal
      and salivary gland epithelium buds to branch rather than to elongate. In
      contrast, mutations that reduced the affinity of the FGF10 for its receptor
      affected the extent, but not the nature, of the response. Our data may provide a
      general model for understanding how binding to HS regulates other morphogenetic
      gradients.

PMID- 19755712
TI  - Charlson Comorbidity Index does not predict long-term mortality in elderly
      subjects with chronic heart failure.
AB  - BACKGROUND: comorbidity plays a critical role in the high mortality for chronic
      heart failure (CHF) in the elderly. Charlson Comorbidity Index (CCI) is the most
      extensively studied comorbidity index. No studies are available on the ability of
      CCI to predict mortality in CHF elderly subjects. The aim of the present study
      was to assess if CCI was able to predict long-term mortality in a random sample
      of elderly CHF subjects. METHODS: long-term mortality after 12-year follow-up in
      125 subjects with CHF and 1,143 subjects without CHF was studied. Comorbidity was
      evaluated using CCI. FINDINGS: in elderly subjects stratified for CCI (1-3 and >
      or =4), mortality was higher in non-CHF subjects with CCI > or =4 (52.4% versus
      70%, P < 0.002) but not in those with CHF (75.9% versus 77.6%, P = 0.498, NS).
      Cox regression analysis on 12 years mortality indicated that both CCI (HR = 1.15;
      95% CI = 1.01-1.31; P = 0.035) and CHF (HR = 1.27; 95% CI = 1.04-8.83; P = 0.003)
      were predictive of mortality. When Cox analysis was performed by selecting the
      presence and the absence of CHF, CCI was predictive of mortality in the absence
      but not in the presence of CHF. CONCLUSION: CCI does not predict long-term
      mortality in elderly subjects with CHF.

PMID- 19755713
TI  - Assessment of functional status and quality of life after percutaneous coronary
      revascularisation in octogenarians.

PMID- 19755714
TI  - The dark side of the immunohistochemical moon: industry.
AB  - Modern biological research is dependent on tools developed and provided by
      commercial suppliers, and antibodies for immunohistochemistry are among the most
      frequently used of these tools. Not all commercial antibodies perform as
      expected, however; this problem leads researchers to waste time and money when
      using antibodies that perform inadequately. Different commercial suppliers offer
      antibodies of varying degrees of quality and, in some cases, are unable to
      provide expert technical support for the immunohistochemical use of their
      antibodies. This article briefly describes the production of commercial
      antibodies from the manufacturer's perspective and presents some guidelines for
      choosing appropriate commercial antibodies for immunohistochemistry.
      Additionally, the article suggests steps to establish mutually beneficial
      relationships between commercial antibody suppliers and researchers who use them.

PMID- 19755715
TI  - Analysis of cell type-specific expression of CK1 epsilon in various tissues of
      young adult BALB/c Mice and in mammary tumors of SV40 T-Ag-transgenic mice.
AB  - Casein kinase 1 epsilon (CK1epsilon) is involved in various cellular processes,
      including cell growth, differentiation, and apoptosis, vesicle transport, and
      control of the circadian rhythm. Deregulation of CK1epsilon has been linked to
      neurodegenerative diseases and cancer. To better understand the cell type
      specific functions of CK1epsilon, we determined its localization by
      immunhistochemistry in tissues of healthy, young adult BALB/c mice and in mammary
      tumors of SV40 T-antigen-transgenic mice. CK1epsilon expression was found to be
      highly regulated in normal tissues of endodermal, mesodermal, and ectodermal
      origin and in neoplastic tissue of mammary cancer. The data presented here give
      an overview of CK1epsilon reactivity in different organs under normal conditions
      and outline changes in its expression in mammary carcinomas. Our data suggest a
      cell/organ type-specific function of CK1epsilon and indicate that tumorigenic
      conversion of mammary glands in SV40 T-antigen-transgenic mice leads to
      downregulation of CK1epsilon. This manuscript contains online supplemental
      material at http://www.jhc.org. Please visit this article online to view these
      materials.

PMID- 19755716
TI  - Genomic, tissue expression, and protein characterization of pCLCA1, a putative
      modulator of cystic fibrosis in the pig.
AB  - Recent studies have identified members of the CLCA (chloride channels, calcium
      activated) gene family as potential modulators of the cystic fibrosis (CF)
      phenotype, but differences between the human and murine CLCA genes and proteins
      may limit the use of murine CF models. Recently established pig models of CF are
      expected to mimic the human disease more closely than the available mouse models
      do. Here, we characterized the porcine CLCA gene locus, analyzed the expression
      pattern and protein processing of pCLCA1, and compared it to its human ortholog,
      hCLCA1. The porcine CLCA gene family is located on chromosome 4q25, with a broad
      synteny with the human and murine clca gene loci, except for a pig-specific gene
      duplication of pCLCA4. Using pCLCA1-specific antibodies, the protein was
      immunohistochemically localized in mucin-producing cells, including goblet cells
      and mucinous glands in the respiratory and alimentary tracts. Similar to hCLCA1,
      biochemical characterization of pCLCA1 identified a secreted soluble protein that
      could serve as an extracellular signaling molecule or functional constituent of
      the protective mucous layers. The results suggest that pCLCA1 shares essential
      characteristics of hCLCA1, supporting the pig model as a promising tool for
      studying the modulating role of pCLCA1 in the complex pathology of CF.

PMID- 19755717
TI  - Identification of a new seven-span transmembrane protein: NGX6a is downregulated
      in nasopharyngeal carcinoma and is associated with tumor metastasis.
AB  - Nasopharyngeal carcinoma (NPC)-associated gene 6 (NGX6) is a novel candidate
      metastasis suppressor gene that can significantly decrease the growth, motility,
      and invasion of NPC cells. In this study, we generated a highly specific NGX6
      polyclonal antibody and analyzed its distribution in the human fetus by Western
      blot and immunohistochemistry. The result of the Western blot showed the protein
      of NGX6 had two types of isoforms, isoform a (NGX6a) and isoform b (NGX6b).
      Isoform a is composed of 472 amino acids with a calculated molecular mass of 52
      kDa, whereas isoform b is composed of 338 amino acids with a calculated molecular
      mass of 37 kDa. It is predicated that there is an epidermal growth factor domain
      in the N terminal of both a and b isoforms, and seven transmembrane domains in
      NGX6a, but only two transmembrane domains in NGX6b. The expression level of NGX6a
      was higher than that of NGX6b in human fetal tissue. Obvious high expression of
      NGX6a protein presents in the nervous system and epithelial tissues of the human
      fetus, but the NGX6b protein (37 kDa) is mainly expressed in the nervous system.
      We further analyzed the tissue microarray, which contained 154 NPC biopsies and
      70 non-NPC biopsies, and found that NGX6a was significantly downregulated in NPC
      and associated with tumor metastasis.

PMID- 19755718
TI  - Gelatin in situ zymography on fixed, paraffin-embedded tissue: zinc and ethanol
      fixation preserve enzyme activity.
AB  - In situ zymography is a method for the detection and localization of enzymatic
      activity in tissue sections. This method is used with frozen sections because
      routine fixation of tissue in neutral-buffered formalin inhibits enzyme activity.
      However, frozen sections present with poor tissue morphology, making precise
      localization of enzymatic activity difficult to determine. Ethanol- and zinc
      buffered fixative (ZBF) are known to preserve both morphological and functional
      properties of the tissue well, but it has not previously been shown that these
      fixatives preserve enzyme activity. In the present study, we show that in situ
      zymography can be performed on ethanol- and ZBF-fixed paraffin-embedded tissue.
      Compared with snap-frozen tissue, ethanol- and ZBF-fixed tissue showed stronger
      signals and superior morphology, allowing for a much more precise detection of
      gelatinolytic activity. Gelatinolytic enzymes could also be extracted from both
      ethanol- and ZBF-fixed tissue. The yield, as analyzed by SDS-PAGE gelatin
      zymography and Western blotting, was influenced by the composition of the
      extraction buffer, but was generally lower than that obtained from unfixed
      tissue.

PMID- 19755721
TI  - Gap formation in transpatellar patellar tendon repair: pretensioning Krackow
      sutures versus standard repair in a cadaver model.
AB  - BACKGROUND: Postfixation loosening within the Krackow stitch-tendon construct may
      be associated with gap formation in patellar tendon repair. HYPOTHESIS:
      Pretensioning the Krackow stitch-tendon construct decreases postfixation gap
      formation in transpatellar patellar tendon repair. STUDY DESIGN: Controlled
      laboratory study. METHODS: Patellar tendon rupture was simulated in 8 pairs of
      cadaveric knees. Standard manual traction was used in all specimens to remove
      Krackow stitch slack. In the experimental group, specimens were pretensioned with
      a simulated active concentric quadriceps contraction with cycling of the knee 10
      times from 90 degrees to 5 degrees of flexion. All specimens were then cycled at
      0.25 Hz from 90 degrees to 5 degrees for 1000 cycles until failure, which was
      defined as 3 or 5 mm of gap formation. RESULTS: A 3-mm gap occurred at 1 cycle
      (mean, 3.5 mm) and 35 cycles (4.0 mm) in the control and experimental groups,
      respectively. Gapping of 5 mm occurred at 35 (5.9 mm) and 100 cycles (5.0 mm) in
      the control and experimental specimens, respectively. Gap formation was smaller
      in the experimental group through 100 cycles (P < .05). CONCLUSION: Gapping was
      lower with pretensioning in the early cycling stages. However, significant
      gapping occurred in both groups with repetitive concentric active loading ranging
      from 90 degrees to 5 degrees of flexion. CLINICAL RELEVANCE: Tightening of the
      Krackow stitch as done in this study does not result in a clinically important
      decrease in gapping. This observation may be generalizable to other applications
      of the Krackow stitch.

PMID- 19755719
TI  - Defining elastic fiber interactions by molecular fishing: an affinity
      purification and mass spectrometry approach.
AB  - Deciphering interacting networks of the extracellular matrix is a major
      challenge. We describe an affinity purification and mass spectrometry strategy
      that has provided new insights into the molecular interactions of elastic fibers,
      essential extracellular assemblies that provide elastic recoil in dynamic
      tissues. Using cell culture models, we defined primary and secondary elastic
      fiber interaction networks by identifying molecular interactions with the elastic
      fiber molecules fibrillin-1, MAGP-1, fibulin-5, and lysyl oxidase. The
      sensitivity and validity of our method was confirmed by identification of known
      interactions with the bait proteins. Our study revealed novel extracellular
      protein interactions with elastic fiber molecules and delineated secondary
      interacting networks with fibronectin and heparan sulfate-associated molecules.
      This strategy is a novel approach to define the macromolecular interactions that
      sustain complex extracellular matrix assemblies and to gain insights into how
      they are integrated into their surrounding matrix.

PMID- 19755722
TI  - Resonant tunneling through S- and U-shaped graphene nanoribbons.
AB  - We theoretically investigate resonant tunneling through S- and U-shaped
      nanostructured graphene nanoribbons. A rich structure of resonant tunneling peaks
      is found emanating from different quasi-bound states in the middle region. The
      tunneling current can be turned on and off by varying the Fermi energy.
      Tunability of resonant tunneling is realized by changing the width of the left
      and/or right leads and without the use of any external gates.

PMID- 19755723
TI  - The large-scale integration of high-performance silicon nanowire field effect
      transistors.
AB  - In this work we present a CMOS-compatible self-aligning process for the large
      scale-integration of high-performance nanowire field effect transistors with well
      saturated drain currents, steep subthreshold slopes at low drain voltage and a
      large on/off current ratio (>10(7)). The subthreshold swing is as small as 45
      mV/dec, which is substantially beyond the thermodynamic limit (60 mV/dec) of
      conventional planar MOSFETs. These excellent device characteristics are achieved
      by using a clean integration process and a device structure that allows effective
      gate-channel-source coupling to tune the source/drain Schottky barriers at the
      nanoscale.

PMID- 19755724
TI  - Experimental and simulation studies of a real-time polymerase chain reaction in
      the presence of a fullerene derivative.
AB  - The real-time polymerase chain reaction of the plant gene heat shock
      transcription factor was fully inhibited in the presence of a fullerene
      derivative C(60)(OH)(20) at a concentration of 4 x 10(-4) mM. This inhibition was
      attributed to the interaction between the nanoparticle and Taq DNA polymerase in
      the reaction. Atomistic molecular dynamics simulations showed a clear tendency
      for hydrogen bonding between C(60)(OH)(20) and both the dNTPs and ssDNA
      components of the polymerase chain reaction. These studies facilitate our
      understanding of the fate of nanoparticles in biomolecular systems, a topic of
      tremendous importance for addressing the biological and environmental
      implications of nanomaterials.

PMID- 19755725
TI  - Wurtzite GaAs/AlGaAs core-shell nanowires grown by molecular beam epitaxy.
AB  - We report the growth of GaAs/AlGaAs core-shell nanowires (NWs) on GaAs(111)B
      substrates by Au-assisted molecular beam epitaxy. Electron microscopy shows the
      formation of a wurtzite AlGaAs shell structure both in the radial and the axial
      directions outside a wurtzite GaAs core. With higher Al content, a lower axial
      and a higher radial growth rate of the AlGaAs shell were observed. Room
      temperature and low temperature (4.4 K) micro-photoluminescence measurements show
      a much higher radiative efficiency from the GaAs core after the NW is overgrown
      with a radial AlGaAs shell.

PMID- 19755726
TI  - Transport properties of single-crystalline n-type semiconducting PbTe nanowires.
AB  - Single-crystalline PbTe nanowires were synthesized using the chemical vapor
      transport method. They consisted of rock-salt structure PbTe nanocrystals
      uniformly grown in the [100] direction. We fabricated field-effect transistors
      using a single PbTe nanowire, providing evidence for its intrinsic n-type
      semiconductor characteristics. The values of the carrier mobility and
      concentration were estimated to be 0.83 cm(2) V(-1) s(-1) and 8.8 x 10(17) cm(
      3), respectively. The Seebeck coefficients (-72 muV K(-1)) of individual
      nanowires were measured to show their n-type carrier-dominated thermoelectric
      transport properties.

PMID- 19755727
TI  - Electromagnetic interference shielding properties of carbon nanotube buckypaper
      composites.
AB  - Preformed carbon nanotube thin films (10-20 microm), or buckypapers (BPs),
      consist of dense and entangled nanotube networks, which demonstrate high
      electrical conductivity and provide potential lightweight electromagnetic
      interference (EMI) solutions for composite structures. Nanocomposite laminates
      consisting of various proportions of single-walled and multi-walled carbon
      nanotubes, having different conductivity, and with different stacking structures,
      were studied. Single-layer BP composites showed shielding effectiveness (SE) of
      20-60 dB, depending on the BP conductivity within a 2-18 GHz frequency range. The
      effects on EMI SE performance of composite laminate structures made with BPs of
      different conductivity values and epoxy or polyethylene insulating layer stacking
      sequences were studied. The results were also compared against the predictions
      from a modified EMI SE model. The predicted trends of SE value and frequency
      dependence were consistent with the experimental results, revealing that
      adjusting the number of BP layers and appropriate arrangement of the BP
      conducting layers and insulators can increase the EMI SE from 45 dB to close to
      100 dB owing to the utilization of the double-shielding effect.

PMID- 19755728
TI  - Nucleation mechanism of GaN nanowires grown on (111) Si by molecular beam
      epitaxy.
AB  - We have performed a real-time in situ x-ray scattering study of the nucleation of
      GaN nanowires grown by plasma-assisted molecular beam epitaxy on
      AlN(0001)/Si(111). The intensity variation of the GaN diffraction peak as a
      function of time was found to exhibit three different regimes: (i) the deposition
      of a wetting layer, which is followed by (ii) a supralinear regime assigned to
      nucleation of almost fully relaxed GaN nanowires, eventually leading to (iii) a
      steady-state growth regime. Based on scanning electron microscopy and electron
      microscopy analysis, it is proposed that the granular character of the thin AlN
      buffer layer may account for the easy plastic relaxation of GaN, establishing
      that three-dimensional islanding and plastic strain relaxation of GaN are two
      necessary conditions for nanowire growth.

PMID- 19755729
TI  - Electron spin for classical information processing: a brief survey of spin-based
      logic devices, gates and circuits.
AB  - In electronics, information has been traditionally stored, processed and
      communicated using an electron's charge. This paradigm is increasingly turning
      out to be energy-inefficient, because movement of charge within an information
      processing device invariably causes current flow and an associated dissipation.
      Replacing 'charge' with the 'spin' of an electron to encode information may
      eliminate much of this dissipation and lead to more energy-efficient 'green
      electronics'. This realization has spurred significant research in spintronic
      devices and circuits where spin either directly acts as the physical variable for
      hosting information or augments the role of charge. In this review article, we
      discuss and elucidate some of these ideas, and highlight their strengths and
      weaknesses. Many of them can potentially reduce energy dissipation significantly,
      but unfortunately are error-prone and unreliable. Moreover, there are serious
      obstacles to their technological implementation that may be difficult to overcome
      in the near term. This review addresses three constructs: (1) single devices or
      binary switches that can be constituents of Boolean logic gates for digital
      information processing, (2) complete gates that are capable of performing
      specific Boolean logic operations, and (3) combinational circuits or
      architectures (equivalent to many gates working in unison) that are capable of
      performing universal computation.

PMID- 19755730
TI  - pH sensor based on boron nitride nanotubes.
AB  - A submicrometer-sized pH sensor based on biotin-fluorescein-functionalized
      multiwalled BN nanotubes with anchored Ag nanoparticles is designed. Intrinsic pH
      dependent photoluminescence and Raman signals in attached fluorescein molecules
      enhanced by Ag nanoparticles allow this novel nanohybrid to perform as a
      practical pH sensor. It is able to work in a submicrometer-sized space. For
      example, the sensor may determine the environmental pH of sub-units in living
      cells where a traditional optical fiber sensor fails because of spatial
      limitations.

PMID- 19755731
TI  - The facet selectivity of inorganic ions on silver nanocrystals in etching
      reactions.
AB  - The facet selectivity of the halide ions and chlorauric acid for several shaped
      silver nanocrystals is presented in this paper. Two inorganic ions show different
      representations when they are used for etching silver nanocrystals in the self
      sacrificial template reaction. The morphological changes of the silver
      nanocrystals indicate that the halide ions prefer to etch the (110) facets of
      silver nanocrystals, while in the chlorauric acid etching reaction, gold first
      modifies the (110) facets and then lets chlorauric acid etch the (111) facets
      instead. The selective facet etching on individual nanoparticles in the solution
      phase has crucial significance in the control-synthesis of nanocrystals and the
      facet asymmetric reaction.

PMID- 19755732
TI  - Fluorescence signals of quantum dots influenced by spatially controlled array
      structures.
AB  - Fluorescence signals of quantum dots (QDs) influenced by different array
      structures of gold-coated silicon nanorods (SiNRs) were investigated via
      experimental observations and two-dimensional (2D) finite element method (FEM)
      simulations. On the densest gold-coated SiNRs array structure, the highest QD
      fluorescence quenching rates were observed and on the sparsest array structure,
      the highest QD fluorescence enhancement rates were observed. By developing a new
      technique which obtains the optical image of the array structures without losing
      information about the QD locations, we were able to further investigate how the
      QD fluorescence is influenced by spatially controlled array structures.

PMID- 19755733
TI  - Immunostimulatory properties and enhanced TNF- alpha mediated cellular immunity
      for tumor therapy by C60(OH)20 nanoparticles.
AB  - Publications concerning the mechanism of biological activity, especially the
      immunological mechanism of C(60)(OH)(20) nanoparticles, are relatively limited.
      However, the structure and characteristics of this carbon allotrope have been
      widely investigated. In this paper, we have demonstrated that water-soluble
      C(60)(OH)(20) nanoparticles have an efficient anti-tumor activity in vivo, and
      show specific immunomodulatory effects to the immune cells, such as T cells and
      macrophages, both in vivo and in vitro. For example, C(60)(OH)(20) nanoparticles
      can increase the production of T-helper cell type 1 (Th1) cytokines (IL-2, IFN-
      gamma and TNF-alpha), and decrease the production of Th2 cytokines (IL-4, IL-5
      and IL-6) in serum samples. On the other hand, C(60)(OH)(20) nanoparticles show
      almost no adverse effect to the viability of immune cells in vitro but stimulate
      the immune cells to release more cytokines, in particular TNF- alpha, which plays
      a key role in the cellular immune process to help eliminate abnormal cells. TNF-
      alpha production increased almost three-fold in treated T lymphocytes and
      macrophages. Accordingly, we conclude that C(60)(OH)(20) nanoparticles have an
      efficient anti-tumor activity and this effect is associated with an increased
      CD(4)(+)/CD(8)(+) lymphocyte ratio and the enhancement of TNF- alpha production.
      The data suggest that C(60)(OH)(20) nanoparticles can improve the immune response
      to help to scavenge and kill tumor cells.

PMID- 19755734
TI  - Campylobacter enteritis in the Arabian Gulf.
AB  - Diarrhoea illnesses constitute a common cause of morbidity and mortality
      worldwide. In recent years, Campylobacter spp. has been recognized as the leading
      cause of bacterial enteritis in both developed and developing countries. The
      biology of Campylobacters as well as the mechanism by which they cause disease is
      yet to be fully explained. In addition, non-availability of fast and reliable
      diagnostic methodology and the growing trend of antibiotic resistance continue to
      pose significant challenges. The absence of national surveillance programs for
      campylobacteriosis, particularly in developing countries, makes it difficult to
      give an accurate picture of the true infection prevalence and the molecular
      epidemiology of isolates circulating in the populations, a situation which had
      hitherto existed in the Arabian Gulf region. However, in recent years, emerging
      data from studies in the Arabian Gulf region has not only enhanced our
      understanding of the epidemiology of Campylobacter both in humans and poultry in
      the region, but has also contributed to the overall understanding of the
      mechanism of Campylobacter enteritis, antibiotic resistance, and improved
      diagnostic approaches. In this review, we examine these emerging data from the
      Arabian Gulf region.

PMID- 19755735
TI  - PCR for M. tuberculosis in tissue samples.
AB  - BACKGROUND: The presence of granuloma, visualized in histopathology for
      diagnosing tuberculosis in tissue samples, is not a specific finding. Moreover,
      histopathological examination of tissue sections needs one to two weeks for final
      reporting. A rapid and sensitive method is therefore needed for detection of
      Mycobacterium tuberculosis in these paucibacillary tissue samples. METHODOLOGY: A
      PCR-assay specific for IS6110 was evaluated for 104 different tissue samples in
      comparison to histopathology that was considered gold standard. RESULTS: PCR
      showed 74.1% sensitivity and 96.1% specificity. False positive and false negative
      results were observed in three (2.88%) and seven (6.73%) samples, respectively.
      Positive agreement between histopathology and PCR was observed as 0.737,
      indicating substantial good agreement between two tests. CONCLUSIONS: PCR can be
      used for early diagnosis of tuberculosis in tissue samples that can help to
      initiate timely anti-tubercular treatment and prevent progression to irreversible
      changes.

PMID- 19755736
TI  - Rational antibiotic use.
AB  - BACKGROUND: Development of resistance to antimicrobial agents and increase of
      cost as the result of unnecessary and inappropriate use of antibiotics has become
      a global health problem. Therefore many strategies, which are aimed at optimizing
      antibiotic therapy, have been developed until now. In Turkey, an antibiotic
      restriction policy as a governmental solution was applied to decrease the
      antibiotic use and especially costs by Ministry of Health in 2003. The aim of
      this study is to evaluate the rational antibiotic use and the impact of the
      implementation of new restriction policy, with their reinforcement by infectious
      disease specialist, on the hospital wide use of antibiotics. METHODOLOGY: The
      data of the inpatients received antibiotics (n=495) during January-June 2006 were
      compared with our previous study performed by the same methodology before the
      restriction policy in 1998. In both studies, prospective active daily
      surveillance of patients was performed by three infectious disease specialists.
      The appropriateness of antibiotic therapy was determined using the criteria
      described by Kunin and Jones. The data were analyzed by using SPSS for Windows.
      RESULTS: While the rate of antibiotic use decreased from 16.6% to 11.3%, rational
      use increased after the restriction policy (p<0.001). Besides the specific
      antibiotic use increasing, prophylactic antibiotic use was found decreased
      (p<0.001). Mostly determined irrationality was the prophylactic uses in both
      studies. As expected, infectious disease specialist examinations resulted in an
      increase in the appropriate antibiotic use. CONCLUSIONS: The restriction policy
      was effective in decreasing the antibiotic consumption and increasing the
      rational antibiotic prescription in our hospital.

PMID- 19755737
TI  - Geophagia as a risk factor for diarrhoea.
AB  - BACKGROUND: Many children under the age of five are exposed to environmental
      health risks in the home environment. These lead to diseases such as diarrhoea,
      which along with acute respiratory infections, malaria and intestinal worms,
      account for 70% of the total health burden to children under five in Kenya. The
      aim of this study was to investigate whether earth eating within the home
      environment by children is a risk factor for diarrhoeal disease. METHODOLOGY: A
      longitudinal study was conducted in 350 households having children aged below
      five years between April and October, 2005. Questionnaire and observation were
      used to collect data on participant demographics, earth eating practices in
      children, incidence of diarrhoea, structure of the home, sanitary facilities
      available, and presence of faecal matter in the yard. RESULTS: Thirty-seven
      percent of index children ingest earth occasionally (less than a handful) and 12%
      ingest a lot (a handful or more). Diarrhoea is positively correlated with earth
      eating (r = 0.306), presence of human faeces in the yard (r = 0.587), presence of
      animal faeces in the yard (r = 0.225) and the index child not wearing loincloth
      (r = 0.471). Chi-square test of independence also indicates that earth eating is
      significantly related to diarrhoea (p<0.005). CONCLUSION: Earth eating is a risk
      factor for diarrhoea in the home environment in this region of Kenya.

PMID- 19755738
TI  - Isolation of Salmonella and Shigella from fish harvested from the Winam Gulf of
      Lake Victoria, Kenya.
AB  - BACKGROUND: Human infections caused by pathogens transmitted from fish are quite
      common. The aim of this study was to isolate enteric pathogenic bacteria from
      fish that might be transmitted to humans after the handling or consumption of
      such fish. METHODOLOGY: One hundred and twenty Nile tilapia fish harvested using
      various fishing methods were collected from fishermen in five fish landing
      beaches within Winam Gulf and disinfected externally using 70% ethyl alcohol for
      2 minutes then washed three times with autoclaved distilled water. Isolation of
      Salmonella and Shigella species from fish samples was performed using standard
      bacteriological procedures. Five milliliters of each fish tissue slurry was
      microbiologically analyzed for any Enterobacteriaceae. Twelve Nile tilapia
      collected from three open-air markets were analyzed for Enterobacteriaceae
      comparison as controls. Identification of Salmonella by using housekeeping genes
      and species-specific primers was performed. RESULTS: Among 120 Nile tilapia, 63
      (52.5%) were infected with Enterobacteriaceae. Out of these, 25 (39.7%) were
      Shigella spp, 9 (14.3%) Salmonella typhimurium, 7 (11.1%) S. typhi, 4 (6.3%) S.
      enteritidis, 16 (25.4%) Escherichia coli, 1 (1.6%) Proteus spp. and Enterobacter
      aerogenes respectively. Ten fish collected from open-air markets yielded E. coli
      (50%), S. typhimurium (20%), S. paratyphi (10%) and S. typhi (20%). CONCLUSION:
      Nile tilapia within Winam Gulf are infected by human enteric pathogens. Shigella
      spp., Salmonella and E. coli were the most frequently isolated, an indication
      that the beaches may be contaminated by untreated municipal sewage, runoff, and
      storm-water. S. typhimurium, S. typhi and S. enteritidis were the most common
      Salmonella isolates.

PMID- 19755739
TI  - Diarrhea and parasitosis in Salta, Argentina.
AB  - BACKGROUND: Salta city is the capital of the province with the same name located
      in the northwest of Argentina. Its great growth over the last decade was not
      organized and the population expanded to occupy places where water and sanitation
      were not yet available. Although the Arenales River, crossing the city, receives
      the impact of point and non-point source pollution, the water is used for many
      purposes, including domestic in the poorest areas, industrial, and recreational
      with children as the main users. According to the World Health Organization, an
      estimated 24% of the global disease burden and 23% of all deaths can be
      attributed to environmental factors. In particular, an estimated 94% of the
      diarrheal burden of disease is attributable to environment, and is associated
      with risk factors such as unsafe drinking water and poor sanitation and hygiene.
      Chronic diarrhea can be caused by an infection or other etiologies; however, most
      of the times the etiological agent is not identified. METHODOLOGY: All the cases
      of diarrhea and parasitosis reported during 2005 in four public health centers of
      the city of Salta were classified by gender and age, analyzed, and represented
      geographically to show areas of higher morbidity rates, which were probably
      related to environmental factors. RESULTS: Water, poor sanitation, and pollution
      are candidate risk factors. Diarrhea cases showed seasonality, with the highest
      incidence during late spring and summer, while parasitosis was persistent
      throughout the year. CONCLUSION: Our spatial analysis permitted us to detect the
      regions of higher incidence of diarrhea and parasitosis during 2005 in the area
      of study.

PMID- 19755740
TI  - Misdiagnosis of an imported case of malaria caused by Plasmodium falciparum.
AB  - An unusual case of malaria presented with gastroenteritis and bloody diarrhoea in
      a 46-year-old male. The patient was a non-Saudi resident of Makkah, Saudi Arabia.
      Fever was not the presenting complaint, and the patient had not experienced any
      chills or sweating. He gave history of recent travel to Pakistan. Initial
      laboratory investigations showed anemia, thrombocytopenia, normal liver function,
      and negative blood film for malaria. His widal, Brucella, and dengue serology was
      negative. Endoscopic examination showed gastroenteritis. On the fifth day of
      admission, a sexual form of Plasmodium falciparum on peripheral smear was
      reported by chance. Malaria was misdiagnosed because of initial negative blood
      film which may have been due to false microscopy or a long period between
      exposures and positive blood film. We concluded that a repeat blood film for
      malaria at 12- to 24-hour intervals for 48 to 72 hours is cost effective when a
      patient has recently travelled to an endemic area.

PMID- 19755741
TI  - PCR detection of Leishmania in skin biopsies.
AB  - INTRODUCTION: Cutaneous leishmaniasis (CL) is an endemic disease and one of the
      major health problems in Morocco. In 2006, the recorded total number of cases of
      CL was 3361, occurring predominantly in the rural population. A new and more
      sensitive diagnostic technique than current methods used is needed in this
      setting. The aim of this study was to assess the efficacy of polymerase chain
      reaction (PCR) to detect leishmanial parasites in skin biopsies of patients from
      different areas of endemicity in Morocco. METHODOLOGY: Biopsies from 26 patients
      with cutaneous ulcers suggestive of leishmaniasis were analysed by PCR using
      primers from the small subunit ribosomal gene. The ability of PCR to detect
      Leishmania was compared with smear-stained and in vitro culture. RESULTS: PCR
      exhibited superior sensitivity (84,6%) compared with direct microscopy smear
      (69,2%) and in vitro culture (69,2%). Our PCR assay also showed good specificity
      (100%). CONCLUSIONS: PCR should be considered a valuable, sensitive, and faster
      diagnostic tool in the diagnosis of cutaneous leishmaniasis, especially for those
      patients with negative parasitologic examination.

PMID- 19755742
TI  - Cutaneous leishmaniasis in Iraq.
AB  - OBJECTIVE: To determine the incidence ofcutaneous leishmaniasis (CL) in Alhaweja
      District and to clarify the secondary bacterial infection inCL. METHODOLOGY: A
      prospective survey was performed in the outpatient clinic of Alhaweja General
      Hospital. All the patients who presented at the dermatology clinic during the
      period from 1 October 2004 to the end of April 2005 were included in the study.
      The provisional diagnosis was dependent on clinical examination; however,
      biopsies and confirmatory tests were performed for questionable cases. Venous
      blood was drawn from patients with cutaneous leishmaniasis for determination of
      IgM. Swabs from the ulcer were taken for culture to determine secondary bacterial
      infections. RESULTS: A total of 107 cutaneous leishmaniasis cases were diagnosed
      during the study period with males representing 57% of the cases. The study
      participants ranged from 1-60 years. The incidence rate was 45 cases per 10,000.
      Clinically, 58% of patients had multiple lesions, while 42% had a single lesion.
      It was found that 36.5% of patients had dry type while 63.5% had wet type
      lesions. Most lesions were found on upper limbs (57%), while the fewest were
      found in the ear 1%. The highest number of cases was recorded during February
      (32.1%), while the lowest rate of cases was recorded in April (3.37%). According
      to cultures and smears, 73% of the cases were positive to giemsa stain and 43%
      were positive in cultures. Secondary bacterial infection occurred in 42% of
      lesions and Staphylococcus epidermidis was the most common bacteria (55%)
      isolated from lesions, followed by Staphylococcus aureus (33%). The mean of total
      IgM levels was significantly decreased in patients with CL in comparison with the
      control group. CONCLUSIONS: CL is endemic in Alhaweja district. CL is an
      important health problem since secondary bacterial infection was reported in 42%
      of cases and this infection my influence the natural course of the disease
      causing more destruction for skin. Giemsa stain was the most sensitive parasitic
      diagnostic test.

PMID- 19755743
TI  - Drug resistance pattern and clonality in H. pylori strains.
AB  - BACKGROUND: This aim of this work was to determine the in vitro activity of
      clarithromycin, amoxycillin, metronidazole and tetracycline against Helicobacter
      pylori and clonality among resistant and sensitive strains isolated from North
      India. METHODOLOGY: A total of 68 H. pylori isolates from peptic ulcer disease
      and non ulcer dyspepsia patients were examined. These strains were subjected for
      determination of minimum inhibitory concentration of clarithromycin, amoxycillin,
      metronidazole and tetracycline. For molecular characterization of resistant and
      sensitive strains, enterobacterial repetitive intergenic consensus sequences
      (ERIC) and random amplified polymorphic DNA-PCR (RAPD-PCR) methods were used.
      RESULTS: All the tested isolates were found resistant to metronidazole, while 65%
      were resistant to amoxycillin and 4.7% were resistant to clarithromycin. However,
      none of the isolates were found to be resistant to tetracycline. Molecular
      fingerprinting and cluster analysis of resistant and sensitive strains did not
      give clues for clonal spread of resistant strains. CONCLUSIONS: Various
      chromosomal mutations were seen in the putative resistance genes of resistant
      strains, possibly indicating selection pressure as the major cause of high
      resistance.

PMID- 19755744
TI  - Antibiotic susceptibility of Helicobacter pylori isolates in Dakar, Senegal.
AB  - BACKGROUND: Helicobacter pylori is the primary cause of peptic ulcer disease and
      an etiologic agent in the development of gastric cancer. A high frequency of H.
      pylori infection has been reported from resource-poor regions. H. pylori
      infection is curable with regimens of multiple antimicrobial agents. However,
      antibiotic resistance is a leading cause of treatment failure. In Africa, there
      are very little data concerning the susceptibility of H. pylori isolates to
      antibiotics. METHODOLOGY: H. pylori isolates from gastric biopsies from
      outpatients > or = 18 years old affected by a gastro-duodenal ulcer were used in
      this study. Susceptibility testing was performed for amoxicillin, ciprofloxacin
      and metronidazole by using the Epsilometer test (E-test) method. RESULTS: H.
      pylori strains were isolated from 40 patients of whom 36 were diagnosed as having
      duodenal ulcer, two with gastric ulcer, and two with gastro-duodenal ulcer.
      Thirty-six (90%) of the isolates were resistant to metronidazole (MICs > or = 8
      microg/l), whereas all isolates were susceptible to amoxicillin (MICs < or = 0.5
      microg/ml) and ciprofloxacin (MICs < or = 1 microg/ml). CONCLUSION: These data
      suggest that metronidazole should not be used therapeutically among Senegalese
      patients in first-line therapy, while ciprofloxacin could be recommended in
      association with amoxicillin and a proton pump inhibitor in Senegal.

PMID- 19755745
TI  - Drug resistance patterns of Salmonella isolates of equine origin from India.
AB  - INTRODUCTION: Salmonellosis is a zoonosis, and one of the most serious public
      health and animal health problems. METHODOLOGY: We studied 111 isolates of
      Salmonella belonging to 14 S. enterica subspecies enterica serovars namely S.
      Abortusequi (45), S. Weltevreden (1), S. Dumfries (2), S. Tshiongwe (1), S.I.
      4,5,12:r,i:1,5 (12), S. Bovismorbificans (3), S. Drogana (8), S. Lagos (4), S.
      Kottbus (3), S. Richmond (1), S. Typhimurium (6), S. Newport (7), S. Paratyphi B
      var Java (17) and S. Saintpaul (5) isolated from equids in India. RESULTS: All
      strains studied were resistant to one or more antimicrobials. Strains were
      resistant to ampicillin (18, 16%), ampicillin+cloxacillin (6, 5%), cefotaxime (6,
      5%), chloramphenicol (2, 2%), ciprofloxacin (9, 8%), gentamicin (27, 24%),
      kanamycin (37, 33%), nalidixic acid (10, 9%), furazolidone (97, 87%),
      streptomycin (33, 30%), sulphamethoxazole (91, 82%), tetracycline (48, 43%) and
      trimethoprim (5, 4.5%). Multiple-drug-resistance was detected in 84 (75.7%)
      isolates and was seen in isolates of all serovars except of S. Kottbus, a rare
      serovar in India. Salmonella isolates could be classified into 51 resistotypes
      but 47 (42.3%) isolates belonged to six major resistotypes. Resistotype 13
      (resistant to furazolidone, sulphamethoxazole and tetracycline) was most common,
      followed by resistotype 19 (resistant to nalidixic acid, sulphamethoxazole and
      tetracycline), resistotype 28 (resistant to furazolidone, streptomycine,
      sulphamethoxazole and tetracycline) and resistotype 40 (resistant to
      furazolidone, gentamycin, kanamycin, streptomycine, sulphamethoxazole and
      tetracycline) including 11, 8, 8 and 7 strains of different serovars,
      respectively. CONCLUSIONS: This study revealed that antimicrobial drug resistance
      was common in Salmonella isolates from equids even towards those drugs not used
      in equids.

PMID- 19755746
TI  - Zimbabwe experiences the worst epidemic of cholera in Africa.
AB  - A severe outbreak of cholera has been reported in Zimbabwe since mid 2008, with
      so far over 92,000 cases and over 4,000 deaths. This outbreak has differed from
      previous outbreaks in being mainly urban and with a high case-fatality rate.
      Breakdown in the supply of clean water has been the main underlying cause but
      breakdown in health service delivery in Zimbabwe has also contributed to the
      magnitude and severity of the outbreak.

PMID- 19755747
TI  - Nosocomial infections and staff hygiene.
AB  - Nosocomial infections are a major source of morbidity and mortality in hospital
      settings. The most important defences against nosocomial transmission of viral,
      bacterial, and other infections are detailed and continuing education of staff
      and strict adherence to infection control policies. The issue is no longer
      whether hand hygiene is effective, but how to produce a sustained improvement in
      health workers' compliance.

PMID- 19755748
TI  - Carotid magnetic resonance imaging. A window to study atherosclerosis and
      identify high-risk plaques.
AB  - Despite recent advances in the understanding and etiology of cardiovascular
      disease, it remains the leading cause of morbidity and mortality worldwide. A
      great deal of research has been dedicated to investigating and identifying plaque
      instability: the so-called "vulnerable plaque". A reliable, in vivo, imaging
      method capable of identifying plaque characteristics associated with high-risk
      plaque will be immensely useful for evaluating plaque status and predicting
      future events. With excellent soft-tissue contrast and resolution, magnetic
      resonance imaging (MRI) has the ability to visualize features of vulnerable
      plaques, as well as perform longitudinal studies on the etiology, progression,
      and regression of atherosclerotic plaque. This review will cover the current
      state-of-the-art and new developments in carotid MRI to characterize
      atherosclerosis and its use in clinical diagnoses and longitudinal studies to
      understand mechanisms of lesion progression and regression.

PMID- 19755749
TI  - Safety and efficacy of transradial vs transfemoral arterial primary coronary
      angioplasty for acute myocardial infarction: single-center experience.
AB  - BACKGROUND: The aim of the present study was to test the hypothesis that the
      transradial arterial approach (TRA) is not inferior to the transfemoral arterial
      approach (TFA) for <or=Killip 3 acute myocardial infarction (AMI) patients
      undergoing primary percutaneous coronary intervention (PCI). METHODS AND RESULTS:
      This study enrolled 506 AMI patients undergoing primary PCI using the TRA (group
      1) between March 2002 and May 2007, and 810 AMI patients undergoing primary PCI
      using TFA (group 2) between May 1993 and February 2002. The results demonstrated
      that puncture to first balloon-inflation time was similar in both groups;
      however, the procedure time was shorter in group 1 than in group 2 (P<0.0001).
      Additionally, the incidences of stenting, tirofiban therapy and final normal
      coronary blood flow of the infarct-related artery were higher, whereas the
      frequency of intra-aortic balloon pump support was lower in group 1 than in group
      2 (all P<0.02). Although the 30-day mortality rate did not differ between the 2
      groups (P=0.341), the rate of combined major vascular and bleeding complications
      was higher in group 2 than in group 1 (P<0.0001). CONCLUSIONS: Initial selection
      of TRA is not inferior to initial selection of TFA for AMI patients undergoing
      primary PCI. However, in the present study, the incidence of combined vascular
      and bleeding complications was lower with the TRA than with the TFA approach.

PMID- 19755750
TI  - Effects of atrial fibrillation on long-term outcomes in patients hospitalized for
      heart failure in Japan: a report from the Japanese Cardiac Registry of Heart
      Failure in Cardiology (JCARE-CARD).
AB  - BACKGROUND: Atrial fibrillation (AF) is a common arrhythmia in patients with
      heart failure (HF), but its prognostic importance is controversial. The effect of
      AF on long-term outcomes, including mortality and rehospitalization, among
      unselected HF patients hospitalized with HF in routine clinical practice in Japan
      was assessed in the present study. METHODS AND RESULTS: The Japanese Cardiac
      Registry of Heart Failure in Cardiology (JCARE-CARD) prospectively studied the
      characteristics and treatment strategies of a broad sample of patients
      hospitalized with worsening HF and the outcomes were followed with an average of
      2.4 years of follow-up. The study cohort (n=2,659) was grouped according to the
      presence (n=937; 35.2%) or absence (n=1,722; 64.8%) of AF at baseline. After
      multivariable adjustment, patients with and without AF had a comparable risk for
      all-cause death (adjusted hazard ratio (HR) 0.931, 95% confidence interval (CI)
      0.690-1.258, P=0.643), cardiac death (adjusted HR 0.949, 95%CI 0.655-1.377,
      P=0.784), rehospitalization because of the worsening HF (adjusted HR 1.028, 95%CI
      0.816-1.295, P=0.816), and all-cause death or rehospitalization (adjusted HR
      1.039, 95%CI 0.842-1.281, P=0.722). CONCLUSIONS: Among patients hospitalized for
      HF in Japan, AF was common, but was not an independent risk for long-term adverse
      outcomes, including death or rehospitalization, in routine clinical practice.

PMID- 19755751
TI  - Pulmonary valve replacement in adult patients with a severely dilated right
      ventricle and refractory arrhythmias after repair of tetralogy of fallot.
AB  - BACKGROUND: Refractory arrhythmias caused by right ventricular (RV) volume
      overload resulting from pulmonary regurgitation are the main concern in adult
      patients after repair of tetralogy of Fallot (TOF). Early pulmonary valve
      replacement (PVR) may prevent irreversible RV dysfunction and refractory
      arrhythmias, so the present study evaluated the PVR outcomes in adult patients
      with a severely dilated RV (d-RV) and refractory arrhythmias after TOF repair.
      METHODS AND RESULTS: Three TOF patients with a d-RV and tachyarrhythmias
      underwent PVR between the ages of 28 and 38 years. All had a d-RV (RV end
      diastolic volume index (RVEDVI) >200 ml/m(2)) with a polymorphic nonsustained
      ventricular tachycardia (NSVT). Atrial tachycardia (AT) was identified in 2
      patients and they underwent radiofrequency catheter ablation. The arrhythmias in
      all 3 were refractory to antiarrhythmic drugs. One year after PVR, the RVEDVI,
      left ventricular ejection fraction, right atrial pressure, cardiac index,
      cardiothoracic ratio, brain natriuretic peptide levels, and peak VO(2) improved
      in all, but without normalization. During the 2.6-3.8 year follow-up, all
      experienced tachyarrhythmias (NSVT or AT), which were controlled with medication.
      CONCLUSIONS: PVR may be beneficial for refractory arrhythmias, even in TOF
      patients with a d-RV, but it is difficult to completely normalize the
      hemodynamics and resolve the arrhythmogenicity.

PMID- 19755752
TI  - Soluble elastin decreases in the progress of atheroma formation in human aorta.
AB  - BACKGROUND: The serum levels of soluble elastin increase in patients with aortic
      dissection, but its distribution and characteristics are unclear. METHODS AND
      RESULTS: The 173 aortic specimens were categorized into 4 groups under microscopy
      (non-atherosclerotic aorta, n=13; fiber-rich plaque, n=77; lipid-rich plaque,
      n=66; ruptured plaque, n=17). Soluble elastin was abundant within the intima of
      both the non-atherosclerotic aorta and fiber-rich plaque, rather than in the
      media, and was decreased within the intima of lipid-rich and ruptured plaques.
      Soluble elastin levels decreased with progress of atherosclerosis (6.0 +/-0.3
      microg/mg protein in non-atherosclerotic aorta; 5.8 +/-0.2 microg/mg protein in
      fiber-rich plaque; 4.9 +/-0.2 microg/mg protein in lipid-rich plaque; 2.8 +/-0.4
      microg/mg protein in ruptured plaque, P<0.05). As well, both matrix
      metalloprotease-9 activity and elastin mRNA expression showed inverse
      distribution against soluble elastin (r=0.437, P<0.0001; r=0.186, P<0.05,
      respectively). Multivariable analysis revealed a decrease in the level of soluble
      elastin in ruptured plaque (2.8 +/-0.4 microg/mg protein in ruptured plaque,
      n=18; 5.5 +/-0.2 microg/mg protein in non-ruptured plaque, n=155, P<0.01).
      Furthermore, western blot showed soluble elastin consists of heterogeneous
      molecular pattern proteins. CONCLUSIONS: Both the synthesis and degradation of
      elastin may be enhanced in active atherosclerotic lesions.

PMID- 19755753
TI  - Ghrelin increases hunger and food intake in patients with restricting-type
      anorexia nervosa: a pilot study.
AB  - Ghrelin increases hunger sensation and food intake in various patients with
      appetite loss. Anorexia nervosa (AN) begins with psychological stress-induced
      anorexia and some patients cannot increase their food intake partly because of
      malnutrition-induced gastrointestinal dysfunction. The effects of ghrelin on
      appetite, food intake and nutritional parameters in anorexia nervosa (AN)
      patients were examined. Five female restricting- type AN patients (age: 14-35 y;
      body mass index: 10.2-14.6 kg/m(2)) had persistently complained of
      gastrointestinal symptoms and failed to increase body weight. They were
      hospitalized for 26 days (6 days' pretreatment, 14 days' ghrelin-treatment, and 6
      days' post-treatment) and received an intravenous infusion of 3 microg/kg ghrelin
      twice a day. Ghrelin infusion improved epigastric discomfort or constipation in 4
      patients, whose hunger scores evaluated by visual analogue scale questionnaires
      also increased significantly after ghrelin infusion. Daily energy intake during
      ghrelin infusion increased by 12-36 % compared with the pre-treatment period.
      Serum levels of total protein and triglyceride as nutritional parameters
      significantly increased after ghrelin treatment. There were no serious adverse
      effects including psychological symptoms. We found that ghrelin decreases
      gastrointestinal symptoms and increases hunger sensation and daily energy intake
      without serious adverse events in AN patients. Although the present study had
      major limitations of the lack of a randomized, placebo-controlled group, non
      blindness of the investigators and the small number of patients recruited, it
      would contribute to further investigations for therapeutic potential of ghrelin
      in AN patients.

PMID- 19755754
TI  - Investigation into the efficacy and safety of octreotide LAR in Japanese patients
      with acromegaly: Shizuoka study.
AB  - The efficacy and safety of the long-acting repeatable formulation of octreotide
      (OCT-LAR) treatment in patients suffering from acromegaly was investigated
      retrospectively in Shizuoka prefecture, Japan. Thirty patients (11 male, 19
      female; average age, 48.9 years old), 29 of whom had undergone transsphenoidal
      surgery previously, were treated with OCT-LAR. OCT-LAR was injected i.m. every 4
      weeks with an intended protocol of 20 mg over 24 months, however, 46.7% of
      patients required the dose of OCT-LAR to be increased. The final average dose of
      OCT-LAR was 25.0 +/- 6.8 mg. Administering OCT-LAR significantly decreased serum
      GH and insulin-like growth factor 1 (IGF-1) levels (from 13.7 +/- 11.9 to 5.8 +/-
      7.3 microg/L and from 585 +/- 263 to 339 +/- 193.7 microg/L after 3 months,
      respectively). Among patients treated with OCT-LAR, 56.7% expressed <or=2.5
      microg/L serum GH and 53.3% displayed serum IGF-1 levels within the normal range,
      while 36.7% met both criteria that indicated treatment success. A sufficient
      outcome was achieved in 73.3% of patients when the rate of GH <or=2.5 microg/L or
      normalization of IGF-1 was accumulated. OCT-LAR did not have a negative effect on
      glucose tolerance when hemoglobin A1c was used as a marker. A gallbladder polyp
      was found only in 1 patient but it was uncertain whether OCT-LAR was involved in
      its development because the patient was not examined before OCT-LAR treatment.
      There were no abnormalities on liver function tests in any patients. In
      conclusion, our results showed that OCT-LAR was safe and effective as a
      therapeutic option for Japanese patients with acromegaly in a postoperative
      setting, by controlling the disease activity.

PMID- 19755755
TI  - Editorial for the manuscript of Zhou and colleagues appearing in this issue:
      Pheochromocytoma and cardioembolic events.

PMID- 19755756
TI  - Abnormal liver function tests and metabolic syndrome--is fatty liver related to
      risks for atherosclerosis beyond obesity?

PMID- 19755757
TI  - Managing depression and the appropriate use of SSRIs and SNRIs in primary care.

PMID- 19755758
TI  - The significance of enzyme immunoassay for the assessment of hepatitis B virus
      core-related antigen following liver transplantation.
AB  - PURPOSE: Recently, a new enzyme immunoassay for the detection of hepatitis B
      virus (HBV) core-related antigen (HBcrAg) has been reported. In this study, we
      proposed to account for feasibility of HBcrAg assay, and discuss the dynamics of
      HBV seen in patients following HBV-related living donor liver transplantation
      (LDLT). METHODS AND RESULTS: This study involved 12 patients; 11 patients had
      positive serum HBcrAg, and 6 patients had negative HBV-DNA. In the post-operation
      period, all cases were negative for HBV-DNA and HBsAg in sera under prophylaxis
      therapy. At post-operation, 5 of the 12 had positive serum HBcrAg, and at stable
      state, 6 had positive serum HBcrAg postoperatively. The mean levels of HBcrAg
      following LDLT were significantly lower than those seen in the preoperative
      operation stage. CONCLUSION: This enzyme immunoassay is a readily utilizable
      marker of HBV replication in the post transplantation stage. Furthermore, the
      evaluation of HBV activity by HBcrAg assay must be studied to determine the
      appropriate prophylaxis for controlling replication of HBV following LDLT.

PMID- 19755759
TI  - Plasma alpha-tocopherol is negatively correlated with hepatocyte apoptosis in
      chronic hepatitis B patients.
AB  - AIM: Hepatocyte apoptosis is involved in the pathogenesis of liver diseases,
      while at the same time oxidative stress plays an important role in liver cell
      damage. This prompted us to evaluate the possible relationship between hepatocyte
      apoptosis and oxidative stress in patients with chronic hepatitis B. METHODS: CHB
      patients were placed in groups A (ALT >40 IU/L) and B (ALT <or=40 IU/L). Healthy
      controls were considered as group C (all ALT <or=40 IU/L). Serum concentrations
      of alpha-tocopherol, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px)
      and malondialdehyde (MDA) were determined and liver cell apoptosis was evaluated
      by using terminal deoxynucleotydil transferase-mediated d-UTP biotin nick-end
      labeling (TUNEL). RESULTS: SOD, GSH-Px, and MDA did not differ between groups.
      alpha-Tocopherol was significantly decreased in groups A (p<0.01) and B (p<0.05)
      when compared with group C and it was negatively correlated with the apoptosis
      index (r=-0.575, p<0.01). CONCLUSION: Only the plasma concentration of alpha
      tocopherol rather than the other oxidative stress markers changed significantly
      in patients with normal alanine aminotransferase levels (ALT <40 IU/L) when
      compared with healthy controls and correlated significantly with the apoptosis
      index, suggesting that alpha-tocopherol may be a possible marker to reflect liver
      cell damage, especially in the absence of serum aminotransferase elevation.

PMID- 19755760
TI  - Relationship between serum bilirubin and carotid atherosclerosis in hypertensive
      patients.
AB  - OBJECTIVE: To investigate the relationship between serum bilirubin and carotid
      atherosclerosis in patients with hypertension. PATIENTS AND METHODS: Carotid
      artery ultrasonography was performed in 198 patients (104 males, average age of
      65.6+/-7.1 years) with hypertension. Serum levels of bilirubin and C-reactive
      proteins (CRP) were measured at the same time. RESULTS: Carotid atherosclerosis
      was detected in 133 patients, 87 of them had carotid artery plaque. The
      prevalence of stroke (20.3%) and myocardial infarction (13.5%) in the
      atherosclerosis group was higher than in the non-atherosclerosis group (9.2% and
      6.2%, respectively, p<0.05). The average total serum bilirubin in the
      atherosclerosis group was lower than in the non-atherosclerosis group (12.8+/-1.3
      vs 16.8+/-1.5 micromol/L, p<0.01), whereas the average serum of CRP was higher
      (4.1+/-1.1 vs 2.3+/-0.7 mg/L, p<0.01). After adjusting other factors such as age,
      total cholesterol, diabetes and systolic blood pressure, total serum bilirubin
      was negatively associated with carotid atherosclerosis in women and men, with
      odds ratios of 0.49 (95% CI, 0.28 to 0.71; p<0.01) and 0.66 (95% CI, 0.46 to
      0.80; p<0.01). Serum CRP was positively correlated to carotid atherosclerosis,
      with odds ratios of 1.76 (95% CI, 1.36 to 2.04; p<0.01) in women and 1.95 (95%
      CI, 1.46 to 2.82; p<0.01) in men. CONCLUSION: Carotid atherosclerosis was
      associated with a high prevalence of stroke or myocardial infarction in
      hypertensive patients. Serum bilirubin was negatively associated with carotid
      atherosclerosis.

PMID- 19755761
TI  - Plasma brain natriuretic peptide as an independent predictor of in-hospital
      mortality after acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: We investigated whether the plasma brain natriuretic
      peptide (BNP) level on admission can serve as a biological marker of in-hospital
      death in patients with acute ischemic stroke. METHODS: We prospectively enrolled
      335 consecutive patients (125 females; mean age, 72.3 years) with acute ischemic
      stroke within 24 hours of onset and measured plasma BNP on admission. Patients
      were divided into two groups: the deceased group, who died during
      hospitalization; and the survival group. The factors associated with in-hospital
      death were investigated by multivariate logistic regression analysis. RESULTS:
      Death was observed in 20 (6.0%) patients. Frequencies of atrial fibrillation,
      cardioembolism, the use of diuretics before ischemic stroke, the use of digitalis
      before ischemic stroke, National Institutes of Health Stroke Scale (NIHSS) score
      on admission, glucose level, and D-dimer were significantly higher in the
      deceased group than in the survival group. On the other hand, albumin was
      significantly lower in the deceased group than in the survival group. The mean +/
      SD of the plasma BNP level of the deceased group was significantly higher than
      that of the survival group (731.5+/-1,070.9 vs. 213.1+/-384.5 pg/mL, p=0.001).
      The optimal cut-off level, sensitivity, and specificity of BNP levels to
      distinguish the deceased group from the survival group were 240 pg/mL, 75.0% and
      73.0%, respectively. Multivariate logistic regression analysis demonstrated that
      a NIHSS score of >13 (odds ratio [OR], 4.87; 95% confidence interval, 1.54 to
      15.44, p=0.007) and plasma BNP level of >240 pg/mL (OR, 4.67; 95% confidence
      interval, 1.28 to 17.09, p=0.020) were independent factors associated with in
      hospital death. CONCLUSION: The plasma BNP level on admission can predict in
      hospital death in patients with acute ischemic stroke.

PMID- 19755762
TI  - LDL cholesterol is more strongly associated with metabolic syndrome in Japanese
      women than in men.
AB  - OBJECTIVE: LDL cholesterol is not usually considered as a component of metabolic
      syndrome (MetS) but rather it is associated with MetS components. METHODS: Data
      from 2,449 men and 1,448 women were examined using receiver operating
      characteristic (ROC) curve for diagnosing MetS and correlation coefficients.
      RESULTS: Blood levels of LDL cholesterol increased more steeply in women than in
      men as the number of MetS components increased. The area under ROC curve (AUC)
      and its 95% confidence interval (CI) of LDL cholesterol for diagnosing MetS were
      0.57 and 0.53-0.60 in men and 0.66 and 0.61-0.71 in women. The optimal cut-off
      point (sensitivity; specificity) of LDL cholesterol was 127 mg/dL (0.50; 0.60) in
      men and 125 mg/dL (0.64; 0.61) in women. Correlations between LDL cholesterol and
      systolic blood pressure, diastolic blood pressure, gamma glutamyltransferase, and
      hemoglobin A1c were stronger in women than in men even after adjustment for age.
      The correlation between LDL cholesterol and blood pressure was significant in
      women, but not in men, even after adjusting for age. CONCLUSION: LDL cholesterol
      was more strongly associated with MetS in Japanese women than in men. The
      correlation between LDL cholesterol and blood pressure was significant in women,
      but not in men.

PMID- 19755763
TI  - Hypertrophy and loss of podocytes in diabetic nephropathy.
AB  - OBJECTIVE: The loss of podocytes has been reported to have a role in the onset
      and progression of diabetic nephropathy (DN). Although structural changes such as
      podocyte hypertrophy are considered to be associated with podocyte loss, the
      relationship has not been thoroughly investigated using human DN renal tissues.
      METHODS: The subjects were 17 patients with DN diagnosed histopathologically by
      renal biopsy. Immunostaining was performed with antibodies for Wilm's tumor 1
      (WT1) and synaptopodin (SPD), which are markers of podocytes, to determine the
      number of podocytes and assess podocyte hypertrophy. RESULTS: The number of
      podocytes was decreased in DN patients compared with the controls. An inverse
      correlation was observed between the number of podocytes and both the urinary
      protein excretion and the extent of mesangial expansion. Podocyte hypertrophy was
      also more marked in DN patients compared with controls. CONCLUSION: Based on
      these results, podocyte loss and hypertrophy were suggested to be involved in the
      development and progression of human DN.

PMID- 19755764
TI  - Association of urinary albumin excretion with insulin resistance in Japanese
      subjects: impact of gender difference on insulin resistance.
AB  - OBJECTIVE: To investigate the relationship between homeostasis model assessment
      for insulin resistance (HOMA-R) and urinary albumin excretion in Japanese and
      clarify gender difference in albuminuria-related insulin resistance. METHODS: The
      subject group consisted of 752 Japanese who had no history of diabetes,
      hypertension or dyslipidemia. After anthropometric examination, fasting blood
      samples were obtained to determine plasma glucose (FPG), lipids and HOMA-R. The
      urinary excretion of albumin in the first void urine was expressed as the
      creatinine ratio (ACR, mg/gCr). Estimated glomerular filtration rate (eGFR) was
      calculated from serum creatinine using the formula for Japanese. RESULTS: HOMA-R
      showed a significant correlation with ACR, and the correlation between HOMA-R and
      ACR was evident in the subjects with central obesity, whereas no significant
      correlation was found in the non-obese subjects. There was no correlation between
      HOMA-R and eGFR. HOMA-R increased according to the quintile of ACR and followed a
      significant trend. This association was obvious in males; however, in females
      there was no significant trend. Multiple regression analysis revealed that HOMA-R
      showed a significant correlation with age, waist circumference, blood pressure
      and serum triglyceride. In addition, ACR exhibited an independent association
      with HOMA-R. The association of HOMA-R and ACR was observed only in males, and
      was not present in females. CONCLUSION: Microalbuminuria is associated with
      insulin resistance in Japanese, where central obesity might play an essential
      role. This association is gender-specific suggesting the involvement of sex
      hormones in the pathogenesis of albuminuria-related insulin resistance.

PMID- 19755765
TI  - Predictive factors of response and survival following chemotherapy treatment in
      acute myeloid leukemia progression from myelodysplastic syndrome.
AB  - OBJECTIVE: The progression of myelodysplastic syndrome to acute myeloid leukemia
      (MDS/AML) is generally incurable and its prognosis is extremely poor. It is
      important to determine the predictive factors of response and survival in
      diseases treated with chemotherapy. METHODS: Twenty-nine patients who had been
      diagnosed of MDS/AML and had undergone chemotherapy between April 2001 and March
      2008 were retrospectively analyzed. RESULTS: Of the 29 patients, 21 patients had
      an abnormal karyotype. Among them, 13 had complex type abnormalities and/or
      monosomy 7. Twenty-four patients were administered a low-dose AraC containing
      regimen and 5 received an AML-like regimen as the initial chemotherapy. The
      responses were CR4/PR2/NR23. The response rate (RR) in the patients with a normal
      karyotype was significantly better than in those with an abnormal karyotype
      (62.5% vs. 4.8%, p=0.003). Univariate analyses showed that the hemoglobin level
      and cytogenetic abnormalities were factors that contributed to the overall
      survival. CONCLUSION: In MDS/AML, patients with a normal karyotype tended to have
      a better response to chemotherapy. The hemoglobin level and cytogenetic
      abnormalities were significant factors affecting the overall survival.

PMID- 19755766
TI  - Prognostic value of magnetic resonance imaging in post-resuscitation
      encephalopathy.
AB  - OBJECTIVE: Prediction of the prognosis of comatose survivors after
      cardiopulmonary arrest (CPA), so-called post-resuscitation encephalopathy (PRE),
      relies on neurological examination findings. Early laboratory indicators of poor
      prognosis (vegetative state/death) are not sensitive enough. METHODS: We analyzed
      the results of magnetic resonance (MR) imaging with fluid-attenuated inversion
      recovery (FLAIR) and diffusion-weighted imaging (DWI) in 22 consecutive patients
      with PRE. Clinical details such as arrest place and anoxia time along with
      neurological examination findings including items of Glasgow coma scale (GCS) and
      the Full Outline of UnResponsiveness (FOUR) score were determined. Receiver
      Operator Characteristics (ROC) curves were produced to determine prognostic yield
      of the parameters studied. RESULTS: Prognosis was classified as 'poor' (Glasgow
      Pittsburg Cerebral Performance -CPC-score 4 or 5) in 16 and 'better' (CPC score 1
      3) in 6 patients. The lower limit of confidence interval (CI) of the area under
      the curve (AUC) of the ROC was higher than 0.5 for visual, motor and total scores
      of GCS and FOUR score. Presence of a lesion pattern of multilobar, or diffuse,
      cortical involvement, termed as "extensive cortical lesion pattern" in MR imaging
      was a very good predictor of poor prognosis with an AUC of ROC of 0,937.
      Sensitivity of GCS motor part score and MR was 87.5% (95% CI: 61.6%-92.6%). Motor
      part of the FOUR score has a slightly lower sensitivity (68.7% with 95% CI from
      41.4% to 88.9%). Incorporating of MR to the motor scores (either GCS or FOUR
      score) improved sensitivity to 100 % (95% CI: 79.2%-100%). AUC of the ROC was
      1.000 (95%CI: 0.844-1.000) for the combination of MR and GCS motor score.
      CONCLUSION: This study provides the preliminary evidence that MRI, when used in
      conjunction with a neurological examination, may have potential in terms of
      predicting outcome in patients with PRE.

PMID- 19755767
TI  - Occupational liver injury due to N,N-dimethylformamide in the synthetics
      industry.
AB  - N,N-dimethylformamide (DMF) is a solvent used extensively in the chemical
      industry. The main toxic effect reported after exposure to DMF is hepatotoxicity.
      We encountered four patients with liver injury due to DMF exposure; the severity
      of the liver injury was related to the exposure levels. After removal of
      exposure, all patients recovered without specific treatment. A careful evaluation
      of occupational history is necessary when liver dysfunction develops in
      industrial workers.

PMID- 19755768
TI  - Cancer of unknown primary site in which tumor marker-oriented chemotherapy was
      effective and pancreatic cancer was finally confirmed at autopsy.
AB  - We report a 47-year-old man with cancer of unknown primary site in whom
      pancreatic cancer was confirmed at autopsy. Although a primary lesion was not
      confirmed, we planned to perform tumor marker-oriented chemotherapy because
      pancreatic cancer was suspected as the primary lesion based on tumor markers and
      pathological findings from metastatic lymph node. Neither S-1 nor gemcitabine was
      effective. However, gemcitabine combined with low-dose cisplatin therapy resulted
      in a marked decrease in the size of tumors. Microscopic examination at autopsy
      revealed poorly differentiated adenocarcinoma in the pancreatic head, although a
      pancreatic mass was not clear macroscopically.

PMID- 19755769
TI  - Jejunogastric intussusception: life-threatening complication occuring 55 years
      after gastrojejunostomy.
AB  - An 80-year-old man presented with acute abdominal pain and hematemesis. He had a
      history of gastrojejunostomy 55 years previously. Ultrasonography (US) showed
      intragastric tublar images with peristalsis. Enhanced computed tomography (CT)
      demonstrated a dilated stomach with an intragastric filling by bowel loops
      suggestive of jejunogastric intussusception (JGI). Reduction of the JGI was
      immediately performed without resection of the intussuscepted intestine, and the
      patient was well postoperatively. JGI is a rare life-threatening complication
      after gastric surgery. This complication may occur even 55 years after gastric
      surgery, and preoperative diagnosis is possible by US and CT findings.

PMID- 19755770
TI  - Small pancreatic cancer with pancreas divisum preoperatively diagnosed by
      pancreatic juice cytology.
AB  - We present a case of small pancreatic head cancer with pancreas divisum
      preoperatively diagnosed by pancreatic juice cytology. A 60-year-old woman was
      referred to our hospital for evaluation of a dilated main pancreatic duct (MPD).
      A small and poorly reproducible low-echoic lesion in the pancreas was suspected
      by ultrasonography (US) and endoscopic ultrasonography (EUS). Magnetic resonance
      cholangiopancreatography (MRCP) failed to visualize the ventral pancreatic duct,
      and the upstream dorsal pancreatic duct was dilated. Endoscopic retrograde
      cholangiopancreatography (ERCP) was indicative of pancreas divisum, and complete
      obstruction of the MPD in the pancreatic head was seen. Cytology of pancreatic
      juice obtained from the dorsal pancreas after minor papilla sphincterotomy
      revealed the presence of adenocarcinoma cells. Pancreatoduodenectomy was
      performed under the diagnosis of pancreatic head cancer with pancreas divisum.
      Histological examination revealed moderately-differentiated tubular
      adenocarcinoma 20 mm in diameter, located in the pancreatic head. Dilatation of
      the dorsal pancreatic duct is sometimes observed in cases with pancreas divisum
      without the presence of tumors. When pancreatic duct stenosis also exists in such
      cases, even if a tumor is not clearly visualized by diagnostic imaging, vigorous
      examinations such as pancreatic juice cytology are recommended to establish an
      accurate diagnosis.

PMID- 19755771
TI  - Penicillin G-induced hemorrhagic cystitis with hydronephrosis.
AB  - Irritable urological symptoms with gross hematuria and bilateral lumbar pain
      developed when the patient received penicillin G for endocarditis. These symptoms
      were followed by renal insufficiency. A contrast-enhanced abdominal computed
      tomography (CT) scan revealed a thickened bladder wall, bilateral hydroureter and
      hydronephrosis, suggesting hemorrhagic cystitis complicated with urinary tract
      obstruction. Urine culture was negative. After discontinuation of penicillin G,
      all symptoms subsided and renal function recovered; hence, penicillin G seems to
      have been associated with hemorrhagic cystitis and acute kidney injury. Positive
      findings in the drug lymphocyte stimulation test (DLST) for penicillin G were
      consistent with this diagnosis.

PMID- 19755772
TI  - Mediastinal pancreatic pseudocysts that were resolved following parathyroidectomy
      for primary hyperparathyroidism.
AB  - Hyperparathyroidism is a rare cause of pancreatic inflammatory disease, however
      their causal relationship has been widely accepted. The appropriate therapy is
      less clear when patients with hyperparathyroidism-associated pancreatitis develop
      complications such as pseudocysts. We describe a 51-year-old woman with primary
      hyperparathyroidism who developed pancreatic pseudocysts extending into the
      mediastinum. After the correction of hyperparathyroidism by removal of a
      parathyroid adenoma, the pseudocysts were resolved and no additional treatment
      was necessary. In patients with primary hyperparathyroidism who develop
      uncomplicated pancreatic pseudocysts, surgical correction of primary
      hyperparathyroidism may precede the interventional treatment on the pancreas when
      possible.

PMID- 19755773
TI  - Gefitinib for non-small cell lung cancer patients with liver cirrhosis.
AB  - Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), such as
      gefitinib or erlotinib, is mainly metabolized in liver. To date, the safety data
      on administrating EGFR-TKI to patients with liver dysfunction is quite limited.
      Here, we administered gefitinib to two adenocarcinoma patients with liver
      cirrhosis, and one patient with EGFR gene mutation in exon 21 achieved long
      stable disease (SD) without any toxicity. Pharmacokinetic data of alternate days
      administration in these patients were similar to those of daily administration in
      patients with normal liver function. Although further studies are needed, a
      reduced dose of gefitinib might be feasible for patients with liver dysfunction.

PMID- 19755774
TI  - Serious venous thromboembolism, heterozygous factor V Leiden and prothrombin
      G20210A mutations in a patient with Klinefelter syndrome and type 2 diabetes.
AB  - Klinefelter's syndrome (KS) is a common cause of man infertility characterized by
      small testes, gynecomastia and hypogonadism. Deep vein thrombosis and
      thomboembolic events are frequent in these patients. Hormone imbalance and co
      existent mutations in the coagulation system may be the primary factors in this
      hypercoagulable state. The increased thromboembolic risk in hypogonadic men has
      been explained by hypofibrinolysis due to androgen deficiency. Regarding the
      association between KS and congenital and acquired thrombophilias, to date, only
      three cases have been. Here, we present the youngest KS case with pulmonary
      thromboembolism with the heterozygous mutations in factor V Leiden and
      prothrombin genes, as detected by further tests. He had the previous diagnosis of
      diabetes mellitus and body mass index was 30 kg/m(2). Our report discusses the
      prothrombotic state in KS patients, with other possible causes for the young
      presentation and the importance of necessary tests in emergency service
      admissions with embolism.

PMID- 19755775
TI  - Thrombotic thrombocytopenic purpura complicated with hypereosinophilic syndrome.
AB  - An 80-year-old woman was referred to our hospital because of eosinophilia and
      thrombocytopenia. She presented with persistent pruritus and cough. Laboratory
      examinations showed persistent eosinophilia, and there was no underlying cause,
      consistent with hypereosinophilic syndrome (HES). After admission, she developed
      a neurological deficit, and microangiopathic hemolytic anemia. She was diagnosed
      with thrombotic thrombocytopenic purpura (TTP) and successfully treated with
      corticosteroids and plasmapheresis. Although TTP has been described in
      association with pregnancy, cancer, collagen diseases, infection, and drug
      intake, hypereosinophilia is not a well-documented cause of this disorder. To our
      knowledge, this is only the second case of TTP with HES, proved to be caused by
      ADAMTS13 inhibitor.

PMID- 19755776
TI  - Successful treatment by all-trans retinoic acid in a patient with acute
      promyelocytic leukemia complicated by liver cirrhosis and polycystic kidney.
AB  - Although all-trans retinoic acid (ATRA) is widely used in acute promyelocytic
      leukemia (APL), there is little data as to whether or not ATRA is useful for
      patients with liver and renal failure. A 63-year-old APL patient, complicated by
      Child-Pugh class A liver cirrhosis and chronic renal failure (creatinine 3.2
      mg/dL), was successfully treated with 45 mg/m(2)/day of ATRA. With three courses
      of chemotherapy, complete remission has been maintained for four years in this
      patient. Serum trough and maximum ATRA concentration, and the area under the
      curve (AUC) were not elevated. These observations suggest that full-dose ATRA
      therapy might be safely applicable to such a complicated case with APL.

PMID- 19755777
TI  - Pure erythroid leukemia with hemophagocytosis.
AB  - A 53-year-old man was admitted with pancytopenia, fever and splenomegaly.
      Biochemistry showed increased ferritin levels. Bone marrow examination revealed
      increased erythrocytic precursors (94.9%) and active hemophagocytosis. Pure
      erythroid leukemia with hemophagocytic syndrome (HPS) was diagnosed. Induction
      chemotherapy comprising idarubicin and cytarabine was administered and steroid
      pulse therapy was added. Complete remission was attained, and HPS also improved.
      However, leukemia relapsed during chemotherapy and the patient died. This is the
      first report of pure erythroid leukemia complicated with HPS.

PMID- 19755778
TI  - Progressive "vascular" corticobasal syndrome due to bilateral ischemic
      hemispheric lesions.
AB  - We report a patient that presented with the corticobasal syndrome (CBS),
      including progressive dementia, asymmetric parkinsonism associated with
      constructional and ideomotor apraxia, action myoclonus and focal hand dystonia.
      Magnetic resonance imaging of the brain revealed extensive ischemic lesions in
      both fronto-temporo-parieto-occipital lobes and steno-occlusion of the middle
      cerebral arteries, bilaterally. This case illustrates that extensive cortical
      vascular-ischemic lesions may present with symptoms mimicking the corticobasal
      syndrome.

PMID- 19755779
TI  - Spontaneous spinal epidural hematoma with unusual hemiparesis alternating from
      one side to the other side.
AB  - A 59-year-old woman suffered from sudden onset of severe neck and back pain. She
      experienced right-side hemiparesis. Although the right-side hemiparesis soon
      disappeared, left-side hemiparesis developed. MRI of the brain was unremarkable.
      MRI of the cervical spine demonstrated hematoma in the left posterior epidural
      space at the C2/3 level. The spinal cord was compressed not only by a
      degenerative disc of the ventral region, but also by hematomas of the dorsal
      region. The unusual hemiparesis alternating from right-side to left-side in this
      case may have been caused by various factors, including cervical canal stenosis,
      the spread of hematoma, disturbance of blood flow, and distribution of stress and
      strain.

PMID- 19755780
TI  - Weil's disease in a patient living in Tokyo.
AB  - A 56-year-old previously healthy man was admitted to our hospital for disordered
      consciousness, anuria, and severe jaundice. The patient had not travelled
      recently, but he worked at a fish market in Tokyo. From his history and clinical
      observation we suspected Weil's disease and started the corresponding treatment.
      Leptospira infection was ultimately confirmed by a serological study. Our report
      raises the awareness that leptospirosis is not only a tropic disease, but also it
      can be a disease in an urban setting in Japan for people who are at risk of
      exposure.

PMID- 19755781
TI  - Utility of follow-up of 131I-MIBG scintigraphy to screen pheochromocytoma.

PMID- 19755782
TI  - Pneumorrhachis with spontaneous pneumomediastinum and subcutaneous emphysema.

PMID- 19755783
TI  - Tracheobronchial amyloidosis in a patient with sarcoidosis.

PMID- 19755784
TI  - Early lesion of Creutzfeldt-Jakob disease detected by standardizing diffusion
      weighted images.

PMID- 19755785
TI  - "Super bone scan" in a case of diffuse bone marrow metastasis of gastric
      adenocarcinoma.

PMID- 19755786
TI  - Idiopathic interstitial pneumonias associated with lung cancer.

PMID- 19755788
TI  - Serum gamma-glutamyl transferase levels are associated with metabolic syndrome in
      community-dwelling individuals.
AB  - AIM: Serum gamma-glutamyl transferase (GGT) activity changes in response to
      oxidative stress. Metabolic syndrome (MetS) is associated with an increased risk
      of major cardiovascular events. Few data are available on the association between
      serum GGT and the prevalence of MetS among community-dwelling individuals in
      Japan. METHODS: We recruited 793 men (mean age, 60+/-14 years), and 1,073 women
      (62+/-12 years), free from any history relating to cardiovascular disease during
      their annual health examination, from a single community. We performed a cross
      sectional study to examine whether serum GGT was associated with MetS. RESULTS:
      The levels of most confounding characteristics varied with increasing GGT
      activity. After adjustment for age, smoking status, drinking status, low-density
      lipoprotein cholesterol, uric acid, estimated glomerular filtration rate and
      alanine aminotransferase, the odds ratios (95% confidence interval) for MetS
      increased across serum GGT tertiles (1, 2.23 (1.224.07), and 2.32 (1.184.56) in
      men; and 1, 1.43 (0.812.51), and 2.64 (1.504.64) in women). After additional
      adjustment for insulin resistance markers (immuno-reactive insulin or
      homoeostasis model assessment of insulin resistance index), the association was
      attenuated and the linear relation no longer significant in both genders.
      Furthermore, serum GGT was significantly associated with the presence of
      individual components of MetS in both genders, except for dyslipidemia in men and
      hypertension in women. CONCLUSIONS: These results suggested that higher serum GGT
      was significantly associated with MetS and its components in the general
      population. This association was related with insulin resistance but was
      independent of other confounding factors.

PMID- 19755789
TI  - Role of Rho/Rho-kinase and NO/cGMP signaling pathways in vascular function prior
      to atherosclerosis.
AB  - AIM: Atherosclerosis is a cardiovascular disease; however, there is little
      information on signal transduction for vascular function in the early stage of
      atherosclerosis. In this work, we investigated the role of Rho/Rho-kinase and
      nitrogen oxide (NO)/cyclic GMP (cGMP) signaling pathways in the aorta prior to
      atherosclerosis. METHODS: Tension, the expression of RhoA protein, Rho-kinase
      activity and the cGMP level were measured using endothelium-intact or -denuded
      aorta prepared from apolipoprotein E-deficient (apoE-KO) and C57BL/6 wild-type
      (WT) mice at 2 months of age. RESULTS: Phenylephrine (PE) induced less maximal
      contraction in the endothelium-denuded aorta from apoE-KO than from WT mice. A
      Rho-kinase inhibitor (Y-27632) reduced more effectively the contraction of apoE
      KO than WT mice, but their RhoA proteins and Rho-kinase activities were not so
      different. Acetylcholine caused larger relaxation of the PE-stimulated,
      endothelium-intact aorta in apoE-KO due to endothelial NO release than WT mice.
      The basal cGMP level in the endothelium-intact aorta of apoE-KO mice was higher
      than that of WT. CONCLUSIONS: Smooth muscle contraction via alpha(1)-adrenergic
      receptor shows higher dependency on Rho-kinase activity, suggesting down
      regulation of the mechanism different from Rho/Rho kinase signaling in the aorta
      prior to atherosclerosis. Endothelium-dependent relaxation is also intensified
      through the NO/cGMP pathway.

PMID- 19755790
TI  - CD40 ligand and MCP-1 as predictors of cardiovascular events in diabetic patients
      with stroke.
AB  - AIM: Up-regulation of soluble CD40 ligand (sCD40L) and of monocyte
      chemoattractant protein-1 (MCP-1) has been found in diabetes and in patients with
      acute cerebral ischemia. We asked whether (i) the two molecules are similarly
      upregulated among non-lacunar and lacunar diabetic strokes and (ii) sCD40L and/or
      MCP-1 predict the risk of cardiovascular events in this setting. METHODS: Ninety
      patients with type 2 diabetes mellitus presenting with an acute ischemic stroke
      (compared with 45 control subjects) were evaluated on admission and up to 36
      months (median 24 months) after the event. RESULTS: Diabetic patients with acute
      stroke had higher plasma CD40L and MCP-1 than controls (p<0.0001), with no
      significant differences among lacunar and non-lacunar strokes. On multiple
      regression analysis, only higher sCD40L quartiles and older age were associated
      with higher MCP-1 quartiles. Forty-eight percent of patients experienced vascular
      events. Cox regression analysis showed that only the presence of higher sCD40L
      values independently predicted the recurrence of vascular events. CONCLUSION: Up
      regulation of inflammatory molecules, such as CD40L and MCP-1, is involved in the
      advanced stage of atherosclerotic cerebro-vascular disease and is associated with
      increased risk of recurrence of cardiovascular events.

PMID- 19755791
TI  - Polymorphisms of fractalkine receptor CX3CR1 gene in patients with symptomatic
      and asymptomatic carotid artery stenosis.
AB  - AIM: The chemokine fractalikine is expressed in vascular endothelium, exerting a
      pro-atherogenic effect. Two single-nucleotide polymorphisms of the CX3CR1 gene
      (T280M and V249I) affect frac-talkine receptor expression and function. We aimed
      to assess the prevalence of CX3CR1 polymor-phisms and the association with
      ischemic cerebrovascular attacks in a cohort of carotid atheromatous disease
      patients and age-matched controls. METHODS: Using PCR-RFLP, we analyzed
      allelotypes for T280M and V249I in 150 patients with and 151 controls without
      carotid atherosclerosis assessed using carotid duplex ultrasound; the subjects
      were patients admitted for any reason to a tertiary hospital. Genotype data were
      compared with modifiable risk factors for cerebrovascular disease and the reason
      for admission, using ischemic stroke as an endpoint. Stroke types associated with
      carotid atherosclerosis were analysed separately. RESULTS: The M280 allelic
      frequency was lower among carotid atherosclerosis patients than controls (0.15
      versus 0.23, adjusted OR 0.47, 95% CI 0.30-0.74). Absence of M280 allele was an
      indepen-dent factor associated with carotid atherosclerosis (OR 3.70, 95% CI 1.92
      7.14), stronger than hypertension, dyslipidemia, diabetes and cigarette smoking.
      The I249 allele was also under-repre-sented in carotid atherosclerosis; this was
      not statistically significant. T280M and V249I genotypes were not associated with
      admission due to ischemic stroke of the large vessel subtype (TOAST classi
      fication, 73 episodes), whereas carotid atherosclerosis, previous ischemic event,
      age, hypertension, diabetes, hyperlipidemia and cigarette smoking were all
      independently associated. CONCLUSIONS: The M280 fractalkine receptor gene allele
      is associated with a lower risk of carotid ath-eromatous disease, independent
      from the modifiable cerebrovascular risk factors.

PMID- 19755792
TI  - Epithelial to mesenchymal transition of lung cancer cells.

PMID- 19755793
TI  - Current situation and future tasks for psychiatric services in Japanese prisons.
AB  - I outline the current situation and future tasks for psychiatric services in
      Japanese prisons. I describe the provision of facilities specializing in
      psychiatric services, preparation of legal aspects related to involuntary
      treatment, provision of therapeutic educational programs regarding addictive
      crimes, and the measures required for continuation of treatment after release
      from prison. I also discuss how, in the current system, under the "Act on Mental
      Care and Treatment for Persons who have Caused Serious Cases under the Condition
      of Insanity," unfairness arises in the treatment of mentally disordered
      offenders, requiring a division between medical care and justice (correctional
      institutions).

PMID- 19755794
TI  - MicroRNA profiling of human intrahepatic cholangiocarcinoma cell lines reveals
      biliary epithelial cell-specific microRNAs.
AB  - Intrahepatic cholangiocarcinoma (ICC), which arises in the small bile ducts of
      the liver, is the second most common liver malignancy. Although modulation of
      microRNA (miRNA) expression has been shown to be a potent sign of malignant
      tumors, miRNA profiles of ICC remains unclear. We performed sequencing analysis
      of the small RNA libraries of 2 ICC cell lines (HuCCT1 and MEC) and one normal
      intrahepatic biliary epithelial cell line (HIBEpiC) to produce the miRNA profiles
      of ICC in vitro. Furthermore, by means of the real-time polymerase chain reaction
      (PCR) we validated the differential expression of miRNAs cloned exclusively or
      predominantly from each of the cell lines. A total of 35,759 small RNA clones
      were obtained from the 3 cell lines. We identified 27 miRNAs that were expressed
      exclusively or predominantly in each cell line. Subsequent validation with the
      real-time PCR confirmed that the miRNAs hsa-miR-22, -125a, -127, -199a, -199a*, 
      214, -376a, and -424 were expressed specifically in HIBEpiC but were
      downregulated in the ICC cell lines. Our study provides important information for
      facilitating studies of the functional role(s) of miRNAs in carcinogenesis of the
      hepatobiliary system. The biliary epithelial cell-specific miRNAs identified in
      this study may serve as potential biomarkers for ICC.

PMID- 19755795
TI  - Dextran sulfate and stromal cell derived factor-1 promote CXCR4 expression and
      improve bone marrow homing efficiency of infused hematopoietic stem cells.
AB  - Although the homing of hematopoietic stem cells (HSC) to the bone marrow (BM) is
      a crucial step in hematopoietic development and BM repopulation, the mechanisms
      underlying these processes have not been fully clarified. Recent studies suggest
      that interaction between the chemokine receptor CXCR4 and its ligand, stromal
      cell-derived factor 1 (SDF-1), plays a critical role in these processes. In
      addition, dextran sulfate increases plasma SDF-1 levels in mice and nonhuman
      primates. Thus, we examined the effects of preconditioning with SDF-1 and dextran
      sulfate on the homing efficiency of HSCs following BM transplantation in mice. We
      found that the preconditioning of donor mice with either SDF-1 or dextran sulfate
      enhanced the homing efficiency of infused HSCs in vivo. The greatest effects were
      obtained with dextran sulfate. Moreover, reverse transcriptase polymerase chain
      reaction analysis demonstrated that SDF-1 and dextran sulfate increased
      transcription of a variety of homing-related genes, including those for CXCR4,
      lymphocyte function associated antigen-1, matrix metalloproteinase-9, very late
      antigen-4/5, and macrophage inflammatory protein-1. We suggest that whereas SDF-1
      directly acts to upregulate CXCR4 expression in HSCs, dextran sulfate acts via
      multiple pathways involved in the induction of various homing-related molecules,
      in addition to SDF-1. Thus, preconditioning donors with dextran sulfate offers a
      novel clinical approach for improving the homing and engraftment of HSCs in the
      BM.

PMID- 19755796
TI  - Symptomatic middle cerebral artery dissection in a young tennis player.
AB  - No information has been available regarding middle cerebral artery (MCA)
      dissection occurring as a result of athletics. We describe a case of cerebral
      infarction in the right MCA region that occurred in young, right-handed tennis
      player while he was serving. Angiography with a contrast medium and a 3
      dimensional rotational system revealed proximal M2 stenosis, and emergency
      superficial temporal artery-MCA anastomosis was performed. As a result, the
      patient showed a complete recovery and resumed all activities of daily life,
      including playing tennis. Because sports such as tennis, in which players
      vigorously swing their heads while serving, could lead to intracranial artery
      dissection, we advise that the possibility of MCA dissection should be considered
      in athletes with certain neurological symptoms, including headache.

PMID- 19755797
TI  - A case of giant mucinous cystic neoplasm of the pancreas resected with
      laparoscopic surgery.
AB  - We report a case of giant mucinous cystic neoplasm (MCN) of the pancreas that was
      successfully treated with laparoscopic surgery. A 29-year-old woman was admitted
      to our hospital for evaluation of an abdominal tumor that had been detected
      during a routine medical examination. The tumor was diagnosed as an MCN of the
      pancreas. We performed laparoscopic distal pancreatectomy and splenectomy. The
      patient could begin oral feeding 3 days after the operation. No complications
      occurred either during or after surgery. The outcome in this patient was
      excellent, with cosmetically acceptable small scars in the skin. Therefore,
      laparoscopic distal pancreatectomy may become a therapeutic option for patients
      with large MCNs of the pancreas.

PMID- 19755798
TI  - Successful transcatheter chemoembolization for acute jaundice in a patient with
      advanced hepatocellular carcinoma and portal vein tumor thrombosis: a case
      report.
AB  - A 54-year-old man with suspected cirrhosis and a hepatic tumor on positron
      emission tomography presented to our hospital for assessment and treatment in
      January 2007. Laboratory tests and diagnostic imaging revealed that the patient
      had cirrhosis due to hepatitis B virus infection and advanced hepatocellular
      carcinoma (HCC) along with portal vein tumor thrombosis (PVTT) (T4N1M0, Child's
      B). After hospitalization, the serum levels of total and direct bilirubin
      increased markedly within several days (26.0 and 20.0 mg/dL), and biliary
      obstruction by the tumor appeared to have caused this sudden jaundice. To treat
      the biliary obstruction, selective transcatheter chemoembolization (TACE) was
      performed via the feeding arteries of the tumor in the anterior segment of the
      right lobe. After TACE, total bilirubin decreased to 7.0 mg/dL, and the patient
      survived for 4 more months.

PMID- 19755799
TI  - A case of metastatic hemangiopericytoma occurring 16 years after initial
      presentation: with special reference to the clinical behavior and treatment of
      metastatic hemangiopericytoma.
AB  - A 40-year-old woman was referred to our Department of Surgery because of an
      abdominal wall mass. Sixteen years earlier, she had undergone surgical resection
      of an inguinal tumor that had been diagnosed as a hemangiosarcoma. Fourteen
      months after the initial resection, the tumor recurred locally, and complete
      resection was performed. Twenty-nine months later, computed tomography showed
      multiple metastatic tumors in the lung. All these tumors were resected during
      thoracoscopic surgery. Thirteen years after the patient's 3rd operation, a firm
      mass was detected in the left lower quadrant of the abdominal wall. Magnetic
      resonance image showed a well-defined mass with heterogeneous contrast
      enhancement within the rectus abdominis muscle. Positron emission tomography
      computed tomography demonstrated no recurrent tumors other than this mass.
      Complete resection was performed. Microscopic examination showed that this tumor
      was composed of hypercellular spindle cells and staghorn-shaped blood vessels.
      The average number of mitotic figures was 28 per 10 high-power fields.
      Immunohistochemical examination of the tumor showed focal positivity for CD34.
      Therefore, the tumor was diagnosed as a metastatic hemangiopericytoma with
      malignant potential. Careful long-term follow-up is required because metastases
      can develop after an extended disease-free interval. Aggressive surgical
      treatment is recommended for distant metastases.

PMID- 19755800
TI  - Referrals during labor in midwifery care.
AB  - In 2008, 84% (459) of 548 women with pregnancies initially considered "low risk"
      requested to give birth under midwifery care at Japanese Red Cross Katsushika
      Maternity Hospital. Of these, 42% (191) were referred to obstetric care during
      labor at term; however, we found no evidence that midwifery primary obstetric
      care is less safe for women with "low-risk" pregnancy than is standard obstetric
      care. Therefore, we recommend that midwifery care be promoted with an
      international collaborative effort.

PMID- 19755801
TI  - Chemoradiation for small cell esophageal carcinoma: report of 11 cases from multi
      institution experience.
AB  - Small cell esophageal carcinoma(SCEC) is a rare disease with aggressive behavior
      and poor prognosis. Because of the rarity of this disease, standard therapy has
      not yet been established. The objective of this retrospective study was to report
      the outcomes of SCEC treated with chemotherapy and radiotherapy from a
      retrospective study of 11 patients. We enrolled 11 SCEC patients who were treated
      with radiation therapy (more than 50 Gy) and chemotherapy between May 1996 and
      October 2007. Patients' age ranged from 44 to 77 years (mean: 69 years). In all
      patients, pathological examination of the specimen obtained by biopsy revealed
      small cell carcinoma. All patients were treated with chemotherapy and radiation
      therapy. The mean follow-up time was 14.7 months, and the median overall survival
      time of all patients was 13.2 months (range: 4.2-43.6 months). The 1-year and 3
      year overall survival rates were 63% and 24%, respectively, while the 1-year and
      3-year progression-free survival rates were 45% and 14%, respectively. Five of
      seven patients with complete response (CR) developed recurrent disease.
      Recurrence sites were distant metastases in four patients and lymph node outside
      the radiation field in one patient. Chemoradiation should be considered as one of
      the important treatment options for the loco-regional control in the patients
      with SCEC.

PMID- 19755802
TI  - Corrugated fiberboard as a positioning insert for patients undergoing
      radiotherapy.
AB  - We have developed a new body fixation system for single patient use, which
      consists of a vacuum cushion, a thermoplastic fixation sheet which is used to
      suppress involuntary and voluntary patient movement, and a triple-wall corrugated
      fiberboard base plate to which both the vacuum cushion and the thermoplastic
      sheet are affixed. To evaluate the characteristics of the fiberboard as a patient
      positioning insert, the photon beam attenuation of a fiberboard base plate, a
      carbon-fiber base plate, and a vacuum-formed cushion were compared. The strength
      of the fiberboard was also evaluated. The attenuation for the carbon-fiber base
      plate was 3.7% and 2.6% in 4 MV and 10 MV photon beams, respectively, while the
      results were less for the fiberboard base plate, i.e. 1.9% and 1.6%. The vacuum
      formed cushion had a minimal effect on transmission. None of the materials
      subsided under the weight loading of 20 g/cm(2). There was no difference between
      the thicknesses of the fiberboard before and after a 50 times daily load with the
      60 kg weight of a volunteer. Corrugated fiberboard is a robust and low
      attenuating material that functions well as a patient-positioning insert.

PMID- 19755803
TI  - Induction of late-onset spontaneous autoimmune thyroiditis by a single low-dose
      irradiation in thyroiditis-prone non-obese diabetic-H2h4 mice.
AB  - The previous data regarding the effect of irradiation on thyroid autoimmunity are
      controversial. We have recently reported the exacerbation of autoimmune
      thyroiditis by a single low dose (0.5 Gy) of whole body irradiation in
      thyroiditis-prone non-obese diabetic (NOD)-H2(h4) mice treated with iodine for 8
      weeks. However, it is uncertain in that report whether the results obtained by
      the provision of iodine in a relatively short period of time (8 weeks) accurately
      reflects the long-term consequences of low-dose irradiation on thyroid
      autoimmunity. Therefore, we repeated these experiments with mice that were
      monitored after irradiation without iodine treatment for up to 15 months. We
      found that a single low-dose (0.5 Gy) irradiation increased the incidence and
      severity of thyroiditis and the incidence and titers of anti-thyroglobulin
      autoantibodies at 15 months of age. The numbers of splenocytes and percentages of
      various lymphocyte subsets were not affected by irradiation. Thus, we conclude
      that low-dose irradiation also exacerbates late-onset spontaneous thyroiditis in
      NOD-H2(h4) mice; one plausible explanation for this may be the acceleration of
      immunological aging by irradiation.

PMID- 19755804
TI  - A special section: the radioadaptive response. Preface.

PMID- 19755805
TI  - Cell cycle perturbations and genotoxic effects in human primary fibroblasts
      induced by low-energy protons and X/gamma-rays.
AB  - The effect of graded doses of high-linear energy transfer (LET) low-energy
      protons to induce cycle perturbations and genotoxic damage was investigated in
      normal human fibroblasts. Furthermore, such effects were compared with those
      produced by low-LET radiations. HFFF2, human primary fibroblasts were exposed to
      either protons (LET = 28.5 keV/microm) or X/gamma-rays, and endpoints related to
      cell cycle kinetics and DNA damage analysed. Following both type of irradiations,
      unsynchronized cells suffered an inhibition to entry into S-phase for doses of 1
      4 Gy and remained arrested in the G(1)-phase for several days. The levels of
      induction of regulator proteins, such as TP53 and CDKN1A showed a clear LET
      dependence. DSB induction and repair as measured by scoring for gamma-H2AX foci
      indicated that protons, with respect to X-rays, yielded a lower number of DSBs
      per Gy, which showed a slower kinetics of disappearance. Such result was in
      agreement with the extent of MN induction in binucleated cells after X
      irradiation. No significant differences between the two types of radiations were
      observed with the clonogenic assay, resulting anyway the slope of gamma-ray curve
      higher than that the proton one. In conclusion, in normal human primary
      fibroblasts cell cycle arrest at the G(1)/S transition can be triggered shortly
      after irradiation and maintained for several hours post-irradiation of both
      protons and X-rays. DNA damage produced by protons appears less amenable to be
      repaired and could be transformed in cytogenetic damage in the form of MN.

PMID- 19755806
TI  - [Meeting of cancer biology with stem cell science].
AB  - Carcinogenic theory is making a unilateral step toward complication, resulting in
      even apparent chaos. Under such chaotic circumstances, a new theory that stems
      from the analogy of cancer cells with stem cells, called cancer stem cell theory,
      is gaining attention. This theory, if correct, necessarily urges two major
      corrections. One is that such complication may not entirely be the cause of
      carcinogenesis and, thus, at least partly, nothing more than a consequence. The
      other is need to create a new framework of cancer therapy. Such a new therapy
      should allow for long-term symbiosis of a patient with cancer cells; a chemical
      compound (drug)-based sustainable therapy that directs the dormancy of cancer
      cells, or converts cancer cells to normal cells (or their resemblances), for
      example.

PMID- 19755807
TI  - [Proper follow-up schedule after curative gastric surgery].
AB  - Although the prognosis of gastric cancer after R0 resection is considered to be
      comparatively satisfactory , some patients experience cancer recurrence according
      to their stage. Recurrence patterns after curative gastrectomy and follow-up
      surveillance were studied. An analysis was done in about 307 (8.0%) patients with
      recurrences of 3,861 primary gastric cancers who underwent R0 resection with
      sufficient lymph node dissection from 1990 to 2006. RESULTS: The median age was
      64 years old, and there were 211 men and 96 women. The recurrence rates were
      hematological 41%, peritoneal 33%, and remote lymph nodal 24%, though peritoneal
      recurrence was most frequent in references. There were many peritoneal and remote
      lymph nodal recurrences in undifferentiated adenocarcinomas, and hematological
      recurrences in differentiated adenocarcinomas. In pT1, hematological recurrences
      were 83% and lymph nodal recurrences were 17%, even after 5 years. In more than
      half, remnant stomach cancers were found, and these cases underwent surgery again
      5 years after primary surgery. The frequency of peritoneal recurrence was
      increased remarkably in pT3 and pT4. The proportion of recurrence was 77% within
      2 years and 91% within 3 years, respectively. There was no difference between
      lymph nodal, hematological and peritoneal recurrence in survival time after
      primary surgery and even after recurrence. Referring to these results, follow-up
      surveillance plans for early and advanced gastric cancers were made. Surveillance
      was to be continued for 10 years after surgery in the early cancers and 5 years
      after surgery in the advanced cancers. Moreover, a mass surveyor complete medical
      checkup was recommended at 5 years after surgery. A standard follow-up plan will
      be made soon for early and advanced gastric cancer patients, respectively, though
      it is not necessarily the same in several institutes. There is no consensus yet
      regarding the intensive follow-up plan after R0 resection, because the evidence
      of efficacy is not yet confirmed. In conclusion, an intensive scientific
      investigation of the follow-up plan is required to determine wether or not there
      are survival benefits.

PMID- 19755808
TI  - [Colorectal cancer].
AB  - Postoperative follow-up provides no evidence of prolongation of the prognosis
      after colorectal cancer surgery. But there is definite evidence of the
      improvement of surgical outcome if the metastatic lesion is respectable. It is
      important to detect a recurrence early and in the respectable state. Establishing
      a good follow-up system is meaningful. The Japanese guideline follow-up planning
      was compared with the ASCO 2005 and ESMO 2009 surveillance recommendations.
      Japanese planning is considered to be clearly more rigorous than those of Europe
      and America and able to discover recurrences early.

PMID- 19755809
TI  - [Hepatocellular carcinoma].
AB  - It is very important for patients after hepatectomy for hepatocellular carcinoma
      that monthly follow-up by tumor makers (AFP/PIVKA-II/AFP-L3) and abdominal
      ultrasound as well as dynamic CT every 4-6 months are conducted for 2 years after
      surgery. When recurrent hepatocellular carcinoma is detected by dynamic CT,
      patients should be treated with anatomic liver resection whenever possible in
      order to obtain good survival.

PMID- 19755810
TI  - [Postoperative follow-up and surveillance for NSCLC patients].
AB  - The following two distinctly different issues should be taken into account when
      planning patient care following curative- intent therapy for non-small cell lung
      cancer(NSCLC): adequate follow-up to manage complications related to the curative
      intent therapy; and surveillance to detect recurrences of the primary lung cancer
      and/or development of a new (second) primary lung cancer early enough to allow
      potentially curative retreatment. The appropriate protocol of postoperative
      surveillance for patients with NSCLC is still controversial. At the moment, a
      clinically reasonable surveillance approach would include a history, physical
      examination and an imaging study (either CXR or CT) every 6 months for 2 years
      and then annually. Recently, there is a wide diversity in the status of
      postoperative patients with NSCLC in Japan. For example, the incidence of
      bronchioloalveolar carcinoma which has a favorable prognosis, small-sized tumor,
      and elderly patients is increased in Japan. Furthermore, adjuvant chemotherapy
      has become a standard therapy for patients with pathologic stage I B, II A, II B,
      and III A around the world. At present, it is recommended that postoperative
      patients be followed based on the current recommended surveillance program with
      several alterations according to their physical and oncological status. An
      appropriate protocol of postoperative surveillance for patients with NSCLC should
      be immediately established.

PMID- 19755811
TI  - [The ideal follow-up after breast cancer operation].
AB  - With the increase in breast cancer patients in Japan, therapy for breast cancer
      has progressed with evidence-based medicine (EBM), and most of it has shifted to
      outpatient clinics (OPC) except for surgery. With the specialization of surgical
      techniques and pharmacological treatments, i. e. sentinel node biopsy and
      advanced medical treatment, many patients now visit specialized cancer clinics,
      and the congestion has resulted in difficulty in follow-up after surgery, and the
      reconsideration of how to follow-up is under way. Although the clinical guideline
      issued by the Japanese Breast Cancer Society recommends performing a careful
      history, physical examination and annual mammography, each clinic has its own
      follow-up program with additional modalities different approaches in EBM. Here we
      investigate the recommendations of the clinical guideline, how they discuss
      evidence, and we attempt to pinpoint the problems when used at the daily clinical
      level while considering the characteristics of current breast cancer practice.
      Then, we considered the specific characteristics of breast cancer revealed by
      meta-analyses, the effect of long-term adjuvant endocrine therapy after surgery,
      and reflecting the patient's intent in follow-up in order to conduct an ideal
      follow-up with a view to cooperation between cancer specialized hospitals and
      community clinics.

PMID- 19755812
TI  - [Chemotherapy with MTX, 5-FU and CDGP for treatment of newly diagnosed head and
      neck cancer].
AB  - Combination chemotherapy including 5-fluorouracil (5-FU) and nedaplatin (CDGP)
      with methotrexate (MTX) and leucovorin(LV)as biochemical modulators was performed
      on patients with newly diagnosed head and neck cancer. We treated 45 patients
      with MTX, 5-FU and CDGP consisting of 150 mg/body of MTX on day 1 followed by a 3
      day continuous infusion of 5-FU at 3,500 mg/m2 and 17 injections of LV at 15 mg
      and infusion of CDGP at 100 mg/m2. Forty-three patients were concurrently treated
      with radiotherapy. Seven of the 45 had distant metastasis. In spite of the
      metastasis, 6 of the 7 underwent radiation therapy only on the primary or
      cervical metastatic mass because their primary tumor was bulky. Treatment
      associated toxicities, e. g., mucositis and myelosuppression were significant but
      acceptable. The overall response rate was 97.6% with 61.9% of CR.

PMID- 19755813
TI  - [Efficacy and safety of high-dose toremifene for hormone-responsive advanced or
      metastatic breast cancer patients with failed prior treatment by aromatase
      inhibitors].
AB  - BACKGROUND: Recently, aromatase inhibitors (AI) are widely used in postoperative
      adjuvant therapy for breast cancer. Nevertheless, studies of postoperative
      therapeutic strategies for recurrent breast cancer are insufficient. SUBJECTS AND
      METHOD: Data on 12 post-menopausal advanced/recurrent breast cancer patients in
      our department during June 2003- April 2007 were used for this study. No patient
      had responded to high-dose toremifene (TOR), a third-generation AI. Their
      therapeutic outcomes were analyzed retrospectively. The median observation period
      of the subjects was 16.1 months (4.0-40.9 months). Subjects were all hormone
      sensitive. Overexpression of HER2 protein was found in only one case. During AI
      therapy immediately prior, exemestane (EXE) and anastrozole (ANA) had been given
      in nine and three cases, respectively. RESULTS: The complete response rate of AI
      therapy was 16.7% (2/12). The clinical benefit rate was 58.3% (7/12). The median
      of time to progression (TTP) was 33.8 weeks. Neither the presence nor absence of
      past history of treatment with tamoxifen (TAM) or other chemotherapies affected
      the anti-tumor effect. Analysis by the site of metastasis or recurrence revealed
      that the therapeutic effects were better for non-life-threatening cases in the
      lung, pleura, soft tissue, etc. The severities of adverse effects were all less
      than grade 2; the major ones were flushing and sweating. CONCLUSION: Results show
      that high-dose TOR given at an early stage can provide clinical benefits for post
      menopausal advanced/recurrent breast cancer not responding to AI.

PMID- 19755814
TI  - [Safety and compliance with UFT (tegafur and uracil) alone and in combination
      with hormone therapy in patients with breast cancer].
AB  - Recently, some new anticancer agents and hormonal agents can be used to treat
      breast cancer, and more patients are administering combinations of these drugs in
      clinical practice. Tegafur and Uracil (UFT) have been widely used for the
      postoperative chemotherapy of breast cancer, and often combined with hormonal
      agents. However, due consideration has not been given to safety and compliance of
      the combined use of UFT and aromatase inhibitor (AI). We therefore studied the
      safety and compliance with UFT alone and in combination with the hormonal agents
      tamoxifen or anastrozole as postoperative therapy in postmenopausal women with
      breast cancer. Our results confirmed that longterm postoperative therapy with UFT
      alone was feasible, provided that early adverse events are carefully monitored.
      Combined therapy was not associated with a significant increase in the incidence
      of adverse events or a decrease in compliance, even in older adult patients.
      Therefore, we consider UFT plus a hormonal agent (especially anastrozole) to be a
      treatment option for patients with HER2-negative highly or incompletely endocrine
      responsive disease who require relatively moderate chemotherapy or for older
      adult patients who require treatment with low toxicity.

PMID- 19755815
TI  - [Effectiveness of S-1 therapy for unresectable/advanced pancreas cancer].
AB  - PURPOSE: Although the susceptibility to chemotherapy of unresectable/advanced
      pancreatic cancer is very poor, the usefulness of new anticancer drugs, such as S
      1, has been reported in recent years. We clinically investigated whether or not S
      1 would prolong survival in this study. OBJECTIVE: 17 unresectable pancreatic
      cancer patients who came for consultation between November 2001 and August 2008
      (ten men, seven women). The average age was 72.5 years and performance statuses
      before medical treatment were 0-2. METHOD: A group of 8 patients did not use S-1
      (non-S-1 group) and a group of a patients (S-1 group)did. The average survival
      period, one-year survival rate, and hospitalization rate were examined. RESULT:
      The average survival period of the non-S-1 group was 173.1 days, and its one-year
      survival rate was 12.5%, compared to 435.1 days and 55.6% in the S-1 group. The
      hospitalization rate was 25.6% in the S-1 group, against 53.1% in the non-S-1
      group. DISCUSSION: S-1 treatment for unresectable/advanced pancreatic cancer
      served to prolong the survival period, suggesting it enabled extension of the
      recuperation-at-home period.

PMID- 19755816
TI  - [Analysis of patients with locally advanced gastric cancer undergoing gastrectomy
      after pre-operative chemotherapy including S-1].
AB  - To improve the prognosis of advanced gastric cancer, various adjuvant therapies
      were tried. We retrospectively examined 7 cases of gastrectomy after pre
      operative chemotherapy using S-1+CDDP, and reported its effectiveness and the
      result. An adverse event of more than Grade 3 showed neutropenia in two cases.
      Anti-tumor effect on the imaging was found in 6 cases of PR and one case of SD.
      We performed gastrectomy within 4 weeks after completion of chemotherapy in each
      case. The histological antitumor effect was more than Grade 2 in four cases, but
      there was no complete response. We compared the overall survival of a patient of
      more than Grade 2 by histological antitumor effect under grade 1b. In the former,
      MST was 982 days and the two-year survival rate was 50.0%; in the latter, MST was
      443 days and the two-year survival rate was 33.3%. We can perform pre-operative
      chemotherapy using S-1+CDDP and expect prognostic improvement for a
      histologically effective case of chemotherapy. If the utility of preoperative
      chemotherapy mainly with S-1 is proved in a phase III trial, this would appear to
      be a therapy of choice for advanced gastric cancer in future.

PMID- 19755817
TI  - [Clinical effects of Hange-shashin-to on combination therapy of S-1/irinotecan
      against the for patients with metastatic gastric and colorectal cancer].
AB  - From July, 2007 to June, 2008, we prospectively investigated the influence of
      Hange-shashin-to on the therapeutic and adverse effects of chemotherapy and the
      changes in quality of life(QOL)scores of the patients with metastatic gastric and
      colorectal cancer. Twenty patients receiving S-1/Irinotecan (CPT-11) therapy were
      randomly allocated into group A (with Hange-shashin-to) and B (without Hange
      shashin-to). While the anti-tumor effects did not differ significantly between
      these two groups, severe side effects of more than grade 3 occurred less
      frequently in group A. Our results suggested that the decrease in QOL scores on
      day 15 might be alleviated in group A, compared to group B. Therefore, Hange
      shashin-to can be one of the useful supportive medicines in the combination
      therapy of S-1/CPT- 11.

PMID- 19755818
TI  - [The efficacy of indisetron hydrochloride for the management of chemotherapy
      induced nausea and vomiting for lung cancer].
AB  - We set out to determine the efficacy of indisetron hydrochloride for the
      management of chemotherapy-induced nausea and vomiting including carboplatin for
      lung cancer. Indisetron hydrochloride was given orally to 32 patients (indisetron
      group), and intravenous 5-HT3 receptor antagonists were given to 24 patients
      (control group). The number of patients with nausea or vomiting occurring within
      24 hours and 24 to 72 hours after chemotherapy was measured. The complete
      inhibition of the vomiting within 24 hours after chemotherapy was 100% in the
      indisetron group and 95.8% in the control group. Twenty-four to 72 hours after
      chemotherapy, the complete inhibition of vomiting rate was 97.1% and 95.8%,
      respectively. In addition, the complete inhibition of nausea rate within 24 hours
      after chemotherapy was 87.5% in the indisetron group and that was 95.8% in the
      control group. The complete inhibition of nausea rate 24 to 72 hours after
      chemotherapy was 56.3% and 70.8%, respectively. No serious adverse events were
      observed. The comparison of the efficacy between the indisetron group and control
      groups did not reach statistical significance (p> 0.05). These findings suggest
      that prophylactic administration of indisetron hydrochloride is useful for the
      inhibition of acute and delayed nausea and vomiting caused by chemotherapy in
      lung cancer patients.

PMID- 19755819
TI  - [Clinical features of acute exacerbation of interstitial pneumonia associated
      with lung cancer after chemotherapy].
AB  - OBJECTIVE: To investigate the incidence and characteristic clinical features of
      acute exacerbation of interstitial pneumonia( IP)associated with lung cancer
      after chemotherapy. METHODS: With this aim, we retrospectively evaluated 41 cases
      of lung cancer associated with IP between January 2004 and December 2006.
      RESULTS: Of 41 patients (male/ female ratio: 40/1, mean age: 71.0+/-7.0 years;
      non-small-cell lung cancer/small-cell lung cancer ratio: 30/11), 4 (9.8%)
      developed acute exacerbation of IP, and 3 died of respiratory failure. There were
      no differences between the acute exacerbation group and the non-exacerbation
      group with regard to the clinical features of IP and chemotherapy regimen.
      Moreover, 5 patients were not diagnosed with IP before chemotherapy. CONCLUSION:
      We conclude that lung cancer patients should be carefully evaluated for
      preexisting IP and that careful informed decision-making regarding chemotherapy
      is crucial in cases of lung cancer associated with IP, because acute exacerbation
      of IP is relatively common, and difficult to predict in association with high
      mortality.

PMID- 19755820
TI  - [An appropriate opioid rotation method for treatment of cancer pain--nationwide
      usage survey of opioid analgesics].
AB  - The use of opioid for treatment of cancer pain has become common with the spread
      of the WHO method for relief of cancer pain. However, it cannot yet be said
      whether such usage is appropriate. To understand how opioid analgesics are
      actually used, we conducted a nationwide mail-based questionnaire survey of
      doctors dealing with cancer pain treatment. Results indicate that at opioid
      rotation to fentanyl patch due to insufficient effect, the second opioid is used
      in a potency equianalgesic or less of the first, so the efficacy of the second is
      often insufficient. In cases where previous medication had an insufficient
      effect, taking rescue doses into account, we believe it is important to rotate
      opioid at 30- 50% above the equianalgesic dose.

PMID- 19755821
TI  - [Assessment of total bilirubin or SN-38/SN-38G ratio as a predictor of severe
      irinotecan toxicity].
AB  - SN-38, an active metabolite of irinotecan (CPT-11), is glucuronidated into SN-38G
      mainly by UGT1A1, during detoxification. However, significant interindividual
      pharmacokinetic variability in SN-38 is caused by factors, including inherited
      predispositions that may affect the function and expression of UGT1A1. Moreover,
      these individual differences can contribute to the development of clinical
      conditions, such as severe leucopenia and diarrhea. Similar to SN-38, bilirubin
      is excreted into bile after being glucuronidated by UGT1A1. Thus, bilirubin is
      metabolized by a mechanism similar to that of SN-38. This suggests that the
      bilirubin level may be an indicator of the adverse effects caused by CPT- 11. On
      the other hand, the ratio between the AUC of SN-38 and the AUC of SN-38G (AUCSN
      38/AUCSN-38G) indicates the ability of SN-38 to be glucuronidated, and is known
      to correlate with leucopenia and diarrhea. However, many blood sampling points
      are required to calculate these AUCs. Therefore, the daily estimation of the
      AUCSN-38/AUCSN-38G values of individual patients is not practical at the clinical
      level. Thus, the objectives of this study were as follows: (1) to establish
      whether or not the total bilirubin level is a useful indicator in predicting the
      development of CPT-11 toxicity. (2) to investigate the correlation of SN-38/SN
      38G (the ratio of the serum concentrations of SN-38 and SN-38G) with AUCSN
      38/AUCSN-38G. Based on the result of this investigation, it will be discussed
      whether or not SN-38/SN-38G may be used as an alternative to AUCSN-38/AUCSN-38G.
      This study included 14 patients with small cell lung cancer or non-small-cell
      lung cancer, in whom serum concentrations of CPT-11, SN-38, and SN-38G were
      measured by HPLC. The results demonstrated a significant correlation between the
      total bilirubin levels prior to chemotherapy and the logarithmic values for AUCSN
      38/AUCSN-38G (r2=0.852). Among the cases with high values for both the total
      bilirubin level and the AUCSN-38/AUCSN-38G ratio, none of the patients had grade
      3 diarrhea, while many cases tended to have grade-3 to -4 neutropenia.
      Additionally, the results of regression analysis suggest that SN-38/SN-38G (2 hr)
      and SN-38/SN-38G (4 hr) might be preferable as a predictive index for AUCSN
      38/AUCSN-38G. These findings suggest that the total bilirubin level and SN-38/SN
      38G, 2 to 4 hours after administration might be used as indicators to predict CPT
      11-induced neutropenia. These indicators are likely to contribute to the
      pharmacogenetic analysis of UGT1A1 genes, as well as individualized therapy, in
      future, and further studies on this subject are expected.

PMID- 19755822
TI  - [How to tell a patient the truth?--a case report from a psycho-oncology
      outpatient clinic].
AB  - Depression and anxiety are common psychiatric syndromes in the cancer population,
      but are not always managed very well due to the barriers to psychiatric
      consultation in Japan. We have tried to care for cancer patients with depression
      or anxiety through our psycho-oncology outpatient clinic. We have found that some
      anxiety in cancer patients derives from miscommunications between patients and
      physicians in charge because physicians do not tell the conditions of diseases
      clearly to patients. Needless to say, physicians should learn the communication
      skills regarding breaking bad news but we would like to emphasize the importance
      of smooth communication among health care professionals through this case report
      which makes us reconsider how we should have told the patient the truth (the time
      for stopping anti-cancer treatment, prognosis and so on) to a patient.

PMID- 19755823
TI  - [A case of inflammatory carcinoma, well-controlled by chemotherapy, especially,
      vinorelbine, S-1 and trastuzumab].
AB  - We experienced a case of inflammatory carcinoma, which has been well controlled
      by chemotherapy, especially, vinorelbine, S-1 and trastuzumab. A 54-year-old
      woman was diagnosed as inflammatory carcinoma with T4d, N3c, M0 in Stage III c.
      The lesion was diagnosed as invasive ductal carcinoma, scirrhous, ER(-), PgR(-),
      HER2(3+) by core needle biopsy, The skin lesion was diagnosed as dermal lymphatic
      carcinomatosis by skin biopsy. The following chemotherapy was performed: FEC(5-FU
      500 mg/m2, epirubicin 70 mg/m2, cyclophosphamide 500 mg/m2) followed by
      docetaxel(DOC 70 mg/m/2), every 3 weeks, each 6 times; after that, sequentially,
      vinorelbine (25 mg/m2)+trastuzumab (2 mg/kg every week), UFT(300 mg,
      daily)+cyclophosphamide (100 mg 2 weeks on, 1 week off)+trastuzumab (continued)
      and S-1 (120 mg/body 4 weeks on, 2 weeks off)+trastuzumab (continued). The
      patient has been well controlled by the chemotherapy with good QOL. Especially
      vinorelbine, S-1, and trastuzumab contributed to the disappearance of skin
      lesion.

PMID- 19755824
TI  - [Combination treatment with trastuzumab and Paclitaxel as primary therapy for
      advanced breast cancer].
AB  - PURPOSES: Despite many recent reports on the effects of trastuzumab for breast
      cancer, many problems remain regarding combination drug treatment and its
      significance. We report our experience with advanced breast cancer patients who
      received combination therapy with trastuzumab+paclitaxel. SUBJECTS AND METHOD:
      Three patients with human epidermal growth factor receptor 2(HER2)-positive
      advanced breast cancer were the subjects. Combination therapy with trastuzumab
      and paclitaxel was carried out as a primary therapy, and its therapeutic effects
      were evaluated based on image findings, tumor markers and observation of resected
      specimens. RESULTS: The primary tumors in the three patients were all clinically
      complete response (cCR). Those in two surgically treated patients were near
      pathologically complete response (pCR), ie, a small amount of cancer cells
      remained in the galactophore, whereas the histological therapeutic effect was
      Grade 2b. In two patients with liver metastases, the metastatic tumor disappeared
      on the image after the therapy. In two patients whose tumor marker was increased
      at the first examination, the level of increase was markedly lowered by the
      therapy. Neither infusion reaction nor heart functional impairment was found in
      any of the three patients. CONCLUSIONS: For patients with advanced breast cancer,
      a regimen containing trastuzumab would produce significant therapeutic effects if
      the cancer is HER2-positive. The regimen would also contribute to the prognosis
      of such patients since it might produce pCR. Since the risk of severe adverse
      effects is low and the treatment with trastuzumab can be conducted safely as an
      ambulatory treatment, high patient QOL seems possible. These findings suggest
      that combination therapy with trastuzumab+paclitaxel is effective as a primary
      therapy for HER2-positive advanced breast cancer.

PMID- 19755825
TI  - [A case of stage IV breast cancer with large cancer ulcer responding to
      combination therapy of capecitabine and medroxyprogesterone acetate and
      cyclophosphamide].
AB  - A 53-year-old woman suffering from nausea and vomiting was admitted to our
      hospital. There was a large ulcer from her left anterior chest to her right side
      chest. After pathological examination from the ulcer, she was diagnosed as breast
      cancer, scirrhous carcinoma. The estrogen and progesterone receptors were
      positive in the tumor. HER2 score was 1+ in the tumor. The stage was
      T4bNxM1(OTH). Uterine metastases of the breast cancer caused obstructive
      nephropathy. Ureteral obstruction was treated by urinary tract catheter. After
      improvement of renal failure, chemotherapy with 5-FU+epirubicin+cyclophosphamide
      (FEC) and docetaxel was performed. The efficacy was judged as stable disease
      (SD). For third-line chemotherapy, she was then treated with oral combination
      chemoendocrine therapy with capecitabine and medroxyprogesterone acetate. After
      the combination chemoendocrine therapy, the local tumor was remarkably reduced.
      With added cyclophosphamide, the partial response (PR) continued for 19 months.
      She died of peritonitis carcinomatosa and pleuritis carcinomatosa. No adverse
      reactions occurred with the combination chemoendocrine therapy. It is suggested
      that this oral combination chemoendocrine therapy may be useful with
      consideration for treatment effectiveness and the quality of life of the patient.

PMID- 19755826
TI  - [Appropriate hemodialysis scheduling based on therapeutic drug monitoring of
      carboplatin in a patient with lung cancer and chronic renal failure].
AB  - A 69-year-old woman undergoing hemodialysis due to ANCA-associated nephritis and
      chronic renal failure developed lung adenocarcinoma and underwent radical
      surgery. Upon recurrence of her cancer, she received combination chemotherapy
      with carboplatin (CBDCA) 150 mg/m2 and docetaxel 35-70 mg/m2. Concentration of
      free CBDCA in serum was monitored for 6 days after drug administration.
      Hemodialysis was performed 1 hour after administration of CBDCA, and on day 4.
      Despite the lower maximum concentration, serum CBDCA levels 20-24 h after
      chemotherapy in this patient were 15 to 20 times higher than in subjects with
      normal renal function who received CBDCA at the area under the curve (AUC) of 5.
      She experienced moderate to severe nausea and vomiting which persisted for 12
      days. During her second course of chemotherapy, hemodialysis was performed for 3
      consecutive days after drug administration. The serum CBDCA levels on day 2 or
      later remained lower than in the first course, and the patient experienced fewer
      severe side effects. Based on the data from therapeutic drug monitoring of CBDCA,
      hemodialysis for 3 consecutive days after drug administration has been
      demonstrated to be useful for treatment of a patient with chronic renal failure
      receiving chemotherapy with CBDCA.

PMID- 19755827
TI  - [A case of advanced non-small-cell lung cancer successfully treated with S-1 plus
      CBDCA after multiple chemotherapy].
AB  - A 51-year-old man consulted our hospital with complaints of a headache and spasm
      of the left upper limbs in January 2007. He was diagnosed as left lung
      adenocarcinoma (c-T2N0M1, stage IV). His serum CEA level was 104.1 ng/mL. After
      the brain tumor extraction, CDDP (80 mg/m2) + GEM (1,000 mg/m2) were administered
      as first-line treatment, and the tumor response was PR (33.3% reduction rate),
      impaired liver function served to interrupt this regimen. Other chemotherapy was
      then conducted in the order of GEM (1,000 mg/m2) + VNR (25 mg/m2), and CBDCA
      (AUC=5) + DOC(60 mg/m2), and the tumor response was NC. As fourth-line treatment,
      S-1 (75 mg/m2, day 1-28, every 6 weeks) + CBDCA (AUC=5, day 8, every 6 weeks) was
      chosen. After 3 courses of the treatment, the serum CEA level normalized, a chest
      CT detected the left lung tumor size reduction (66.7% reduction rate), and an
      abdominal CT detected disappearance of the left adrenal gland tumor. In January
      2008, left upper lobectomy and lymph node resection (ND2a) were performed.
      Histopathological examination of the lung tumor showed viable adenocarcinoma
      cells. Postoperatively, S-1+CBDCA also was administered in a 3-course treatment.
      This patient is currently continuing treatment with S-1 monotherapy with no
      recurrence. This case suggests that S-1+CBDCA may be an effective treatment in
      patients with advanced non-small-cell lung cancer even after multiple
      chemotherapy.

PMID- 19755828
TI  - [A case of superficial small cell carcinoma of the esophagus].
AB  - A 69-year-old man complaining of odynophagia visited a nearby hospital, and was
      referred to our hospital with endoscopic findings showing a flat-elevated lesion
      35 cm from the incisors. Biopsy in our hospital revealed small cell carcinoma
      with a squamous cell carcinoma component. Thoracoabdominal enhanced CT detected
      neither lymph node metastases, nor distant organ metastases. We selected subtotal
      esophagectomy and retrosternal reconstruction of gastric tube. Since small cell
      carcinoma of the esophagus has a dismal prognosis, we conducted a minimally
      invasive operation with two-field lymph node dissection from the standpoint of
      local treatment, then shifted early to postoperative chemotherapy. The
      pathological diagnosis was an undifferentiated carcinoma, small cell type, inf
      beta, pT1b (pSM), ie (-), ly0, v1, pIM0, pN0. Postoperatively, he underwent
      chemotherapy with CDDP+CPT-11 following small cell carcinoma of the lung. Here
      mains alive without evidence of recurrence in the two years three months since
      the operation.

PMID- 19755829
TI  - [A case of advanced gastric cancer successfully treated by combination therapy of
      S-1 and docetaxel].
AB  - A 73-year-old man with gastric cancer of Borrmann type 3 accompanied with N3 was
      treated by combination therapy of S-1 and docetaxel (DOC). He received DOC
      intravenously at 45 mg/m/2 on day 1 and 15, and S-1 orally at 120 mg/body on day
      1 to 7 and day 15 to 21. This treatment was repeated every 28 days as one course.
      After 4 courses of treatment, a CT scan revealed partial response of the lymph
      node metastases, and imaging modalities showed complete response of the primary
      lesion. The serum CEA value normalized after 4 courses of treatment. Toxicities
      included leukocytopenia (grade 3-4) and neutropenia (grade 3-4). Chemotherapy in
      the outpatient setting was possible by reduction of dose (DOC 45-->40-->35
      mg/m2). Total gastrectomy was performed after 4 courses of treatment. The
      histological effect of primary lesion was judged to be Grade 2.

PMID- 19755830
TI  - [A case of gastric cancer with peritoneal dissemination-efficacy of combination
      therapy with S-1 and docetaxel].
AB  - The efficiency of new anti-cancer drugs such as the S-1 system was demonstrated
      in a controlled study comparing treatment and non-treatment groups. We
      encountered a patient with gastric cancer demonstrating peritoneal dissemination,
      who was successfully treated by combination therapy using S-1 and docetaxel. A 62
      year-old woman was admitted to the hospital due to appetite loss and nausea.
      Upper GI endoscopy demonstrated a type 3 gastric cancer extending from the upper
      to lower body of the stomach. In the pelvic cavity, an abdominal CT scan
      demonstrated massive ascites. An abnormally high CA72-4 (143.8 U/mL) level was
      detected in serum. Treatment with S-1 and docetaxel was started with the
      following regimen: daily oral administration of 80 mg/body S-1 for 14 days,
      followed by a 7-day rest and infusion of 40 mg/m2 docetaxel on day 1. After 4
      courses, the sites of dissemination had disappeared, and the serum CA72-4 value
      returned to normal. The patient clinically achieved good QOL by this method,
      which was very effective for non-resected gastric cancer with peritoneal
      dissemination.

PMID- 19755831
TI  - [A case of advanced cancer of the gastric remnant with complete response to S-1
      plus docetaxel chemotherapy as confirmed histopathologically].
AB  - A 64-year-old man underwent a probe laparotomy for unresectable gastric remnant
      cancer (GRC) involving the pancreas and retroperitoneum. Combination chemotherapy
      with S-1 and docetaxel was given after surgery. Computed tomography and endoscopy
      showed tumor shrinkage after two courses of chemotherapy. After 6 courses,
      endoscopic examination revealed a small ulcer. Although no cancer cells were
      found in a biopsy specimen, we were unable to conclude that such cells had
      disappeared completely. The patient underwent resection of GRC with
      pancreatosplenectomy. The remnant stomach could not be dissected from the
      pancreas, and we suspected the presence of residual cancer cells. The tumor was
      found to have had a complete response (CR) to combination chemotherapy on
      histopathological examination.

PMID- 19755832
TI  - [A case of gastric cancer with posterior mediastinal lymph node metastasis
      responding to combination therapy of Paclitaxel and S-1].
AB  - The patient was a 73-year-old man who was hospitalized with advanced gastric
      cancer. Computer tomography showed multiple liver and mediastinum lymph node
      metastases. Therefore, he was diagnosed as unresectable gastric cancer(Stage IV).
      We attempted low-dose combination therapy of CDDP and S-1, but it was ineffective
      against advance gastric cancer. We decided to change the chemotherapy, using
      combination therapy of paclitaxel and S-1. In the regimen, paclitaxel (60 mg/m/2)
      was administered on day 1, day 8, and day 15. S-1 (80 mg/m2) was administered 4
      weeks with a 2-week rest. After the 2 courses, computer tomography showed
      reduction of the liver metastasis and disappeared of the lymph node metastases.
      Therefore, he could undergo total gastrectomy and radiofrequency ablation of
      liver metastases. He continued this combination therapy one year after the
      operation. The cancer has not recurred thus far. When combination chemotherapy of
      paclitaxel and S-1 was effective against Stage IV gastric cancer, we suggested
      that radical surgery is possible for those cases.

PMID- 19755833
TI  - [A case of cardiac tamponade induced by gastric cancer responding to S-1].
AB  - A 56-year-old man was admitted to our hospital for gastric cancer. He had dyspnea
      before admission. Chest CT scan showed massive pericardial and pleural effusion.
      He was treated by cardiac drainage, and cytology of the effusion showed class V.
      We injected mitomycin C 10 mg into the pericardiac cavity, and also administered
      S-1 100 mg per day. His dyspnea improved and he was discharged. Afterward the
      dyspnea re-appeared, and he died 9 months after the diagnosis. We report this
      rare case of cardiac tamponade induced by gastric cancer responding to S-1 with a
      review of the literature.

PMID- 19755834
TI  - [Difficult management of warfarin anticoagulant therapy due to S-1 administration
      for gastric cancer--report of a case].
AB  - A 72-year-old male with gastric cancer was referred to our hospital. The patient
      had been administered warfarin for cerebral infarction, aspirin and clopidogrel
      sulfate after percutaneous coronary intervention (PCI). Distal gastrectomy was
      performed for the lesion after discontinuing these drugs. After operation,
      warfarin was administered again as soon as possible, and on the other hand, we
      started treating the patient with S-1 for adjuvant chemotherapy carefully,
      because the interaction of each drug had been described before. On the sixth day
      after starting S-1, we reduced the amount of warfarin because PT-INR was elevated
      to a extremely high level of 6.84. Seven days later, PT-INR recovered to a
      slightly high level of 2.17. With continuation of S-1, PT-INR showed large
      fluctuations, so we needed to regulate the amount of warfarin carefully. It is
      important that we recognize the possibility of immediate interaction of two drugs
      and, before these drugs are administered, inform the patient about it.

PMID- 19755835
TI  - [A case of paclitaxel-induced peripheral neuropathy successfully treated by H2
      blocker, lafutidine].
AB  - We report a 75-year-old female gastric cancer patient with paclitaxel-induced
      peripheral neuropathy, which was successfully treated by the H2-blocker,
      lafutidine. From December 2007, she underwent second-line chemotherapy using
      paclitaxel (80 mg/m/2 day 1, 7, 14/28 days) for peritoneal dissemination which
      had been refractory to first-line chemotherapy using S-1 (80 mg/m / 2, day 1
      28/42 days). After 2 courses, CT showed a complete response (CR) of the
      peritoneal dissemination. However, at the same time peripheral neuropathy
      appeared, which was aggravated to grade 3 at the 6th course. Beginning with the
      7th course, we administered lafutidine (10 mg/day) for peripheral neuropathy,
      which recovered to grade 1 after 14 days of lafutidine administration. Lafutidine
      was administered until July 2008, when peripheral neuropathy kept grade 1 without
      lafutidine. After 9 courses, paclitaxel therapy failed because of general
      fatigue.

PMID- 19755836
TI  - [A case report of primary duodenal adenocarcinoma with marked lymph node
      metastases responding to chemotherapy with S-1 plus CDDP combination].
AB  - The patient was a 48-year-old female who underwent combination chemotherapy of S
      1 plus CDDP after diagnosis of primary duodenal adenocarcinoma with marked lymph
      node metastases. The regimen was as follows: 80 mg/m2 of S-1 on days 1-21 orally
      and 60 mg/m2 of CDDP on day 8 intravenously. One course lasted for 5 weeks. After
      5 courses, metastasized lymph nodes were remarkably reduced. This case suggests
      that the combination of S-1 and CDDP may be an effective regimen for advanced
      primary duodenal adenocarcinoma.

PMID- 19755837
TI  - [Long survival of a case of unresected duodenal cancer treated by S-1 before and
      after duodenojejunostomy].
AB  - A 52-year-old woman visited our hospital with epigastralgia. Detailed examination
      revealed a duodenal cancer of the ascending limbs. Since she refused the
      resection, the administration of S-1 alone was commenced. After one course of
      this treatment, oral intake became impossible. Duodenography and endoscopy showed
      duodenal obstruction, and she underwent surgery. The tumor proved to be
      unresectable due to direct invasion of the inferior vena cava. Duodenojejunostomy
      was performed. After surgery, she was treated by S-1 and survived 2 years and 11
      months, which resulted in 3 years and 2 months' long survival from her first
      visit. The intervals of the intake and home stay, after the operation, were 2
      years and 8 months and 2 years and 5 months, respectively. The combination of S-1
      administration and bypass operation provides a useful alternative for the
      treatment of unresectable duodenal cancer with stenosis.

PMID- 19755838
TI  - [A case of rectal cancer with liver metastases successfully treated with modified
      FOLFOX6 therapy].
AB  - We report a case of a 71-year-old male with rectal cancer accompanied by liver
      metastases. Abdominal CT scan revealed a hepatic tumor (S2, 3) about 4 cm in
      diameter. We performed a Mile's operation and planned to resect the liver
      metastases after chemotherapy of modified FOLFOX6(mFOLFOX6)regimen: l-leucovorin
      (200 mg/m2) and oxaliplatin (85 mg/m/2) were given as a 2-hour infusion followed
      by bolus injection of 5-FU 400 mg/m2 and a 46-hour infusion 5-FU 2,400 mg/m2
      every 2 weeks. An abdominal CT scan 6 months later demonstrated regression of the
      liver metastases. Hepatectomy was performed after chemotherapy, and no viable
      tumor cells were seen.

PMID- 19755839
TI  - [A case of simultaneous bilateral metastatic ovarian tumor of colon cancer
      followed by FOLFOX4 Regimen and oral tegafur/uracil+oral leucovorin after R0
      operation].
AB  - The patient was a 41-year-old female, who underwent histectomy and sdnexopexy due
      to perforated ovarian tumor. One month later, she was diagnosed with simultaneous
      bilateral metastatic ovarian tumor of colon cancer, and right hemicolectomy (D3)
      was performed. After surgery, the patient was treated with 10 courses of therapy
      with the FOLFOX4 regimen. No recurrence was recognized, and the patient was
      treated with 12 courses of therapy with oral tegafur/ uracil (UFT)+oral
      Leucovorin (LV). The patient evidenced no tumor recurrence 2 years after the
      initial treatment. We consider oral UFT+oral LV therapy was useful for post
      FOLFOX4 therapy after R0 surgery.

PMID- 19755841
TI  - BRIT1/MCPH1 is a multifunctional DNA damage responsive protein mediating DNA
      repair-associated chromatin remodeling.

PMID- 19755840
TI  - The evolutionarily conserved RNA binding protein SMOOTH is essential for
      maintaining normal muscle function.
AB  - The Drosophila smooth gene encodes an RNA binding protein that has been well
      conserved through evolution. To investigate the pleiotropic functions mediated by
      the smooth gene, we have selected and characterized two sm mutants, which are
      viable as adults yet display robust phenotypes (including a significant decrease
      in lifespan). Utilizing these mutants, we have made the novel observation that
      disruption of the smooth/CG9218 locus leads to age-dependent muscle degeneration,
      and motor dysfunction. Histological characterization of adult sm mutants revealed
      marked abnormalities in the major thoracic tubular muscle: the tergal depressor
      of the trochanter (TDT). Corresponding defects include extensive loss/disruption
      of striations and nuclei. These pathological changes are recapitulated in flies
      that express a smooth RNA interference construct (sm RNAi) in the mesoderm. In
      contrast, targeting sm RNAi constructs to motor neurons does not alter muscle
      morphology. In addition to examining the TDT phenotype, we explored whether other
      muscular abnormalities were evident. Utilizing physiological assays developed in
      the laboratory, we have found that the thoracic muscle defect is preceded by
      dysmotility of the gastrointestinal tract. SMOOTH thus joins a growing list of
      hnRNPs that have previously been linked to muscle physiology/pathophysiology. Our
      findings in Drosophila set the stage for investigating the role of the
      corresponding mammalian homolog, hnRNP L, in muscle function.

PMID- 19755842
TI  - The protein tyrosine phosphatase receptor D, a broadly inactivated tumor
      suppressor regulating STAT function.

PMID- 19755843
TI  - On the origins of ultra-fine anaphase bridges.

PMID- 19755844
TI  - Co-ordinated regulation of translation following DNA damage.

PMID- 19755845
TI  - The type III TGFbeta receptor regulates directional migration: new tricks for an
      old dog.
AB  - The type III transforming growth factor beta (TGFbeta) receptor (T beta RIII or
      betaglycan) is a TGFbeta superfamily co-receptor. Loss of T beta RIII expression
      occurs in a broad spectrum of human cancers including cancers of the breast,
      kidney, lung, ovary, pancreas and prostate. T beta RIII suppresses cancer
      progression, in part, by reducing cancer cell motility. This T beta RIII function
      is independent of its TGFbeta signaling role, with T beta RIII activating Cdc42
      via its interaction with the scaffolding protein beta-arrestin2 to re-organize
      the actin cytoskeleton, decrease directional persistence and inhibit random
      migration in both epithelial-derived cancer cells and normal epithelial cells.
      These studies contribute to a growing body of literature supporting essential and
      non-redundant roles for T beta RIII and emphasize the importance of continued
      investigation of T beta RIII and other signaling co-receptors.

PMID- 19755846
TI  - LINE-1 DNA methylation is inversely correlated with cord plasma homocysteine in
      man: a preliminary study.
AB  - Folic acid supplementation during pregnancy has known beneficial effects. It
      reduces risk of neural tube defects and low birth weight. Folate and other one
      carbon intermediates might secure these clinical effects via DNA methylation.
      However, most data on the effects of folate on the epigenome is derived from
      animal or in vitro models. We examined the relationship between cord blood
      methylation and maternal folic acid intake, cord blood folate and homocysteine
      using data from 24 pregnant women. Genome-wide methylation was determined by the
      level of methylation of LINE-1 repeats using Pyrosequencing. We show that cord
      plasma homocysteine (p = 0.001, r = -0.688), but not serum folate or maternal
      folic acid intake, is inverse correlated with LINE-1 methylation. This remained
      significant after correction for potential confounders (p = 0.004). These data
      indicate that levels of folate-associated intermediates in cord blood during late
      pregnancy have significant consequences for the fetal epigenome.

PMID- 19755847
TI  - Real-time case fatality analysis points to emerging evidence of increasing
      severity of pandemic (H1N1) 2009.

PMID- 19755848
TI  - Attenuation of constitutive ATM activation and H2AX phosphorylation in human
      leukemic TK6 cells by their exposure to static magnetic field.

PMID- 19755849
TI  - GHRH antagonist causes DNA damage leading to p21 mediated cell cycle arrest and
      apoptosis in human colon cancer cells.
AB  - We investigated the mechanisms of inhibitory effect of growth hormone-releasing
      hormone (GHRH) antagonist JMR-132 on the growth of HT29, HCT-116 and HCT-15 human
      colon cancer cells in vitro and in vivo. High-affinity binding sites for GHRH and
      mRNA for GHRH and splice variant-1 (SV1) of the GHRH receptor were found in all
      three cell lines tested. Proliferation of HT-29, HCT-116 and HCT-15 cells was
      significantly inhibited in vitro by JMR-132. Time course studies revealed that
      the treatment of human HCT-116 colon cancer cells with 10 muM GHRH antagonist JMR
      132 causes a significant DNA damage as shown by an increase in olive tail moment
      (OTM) and loss of inner mitochondrial membrane potential (Delta Psi m). Western
      blotting demonstrated a time-dependent increase in protein levels of phospho-p53
      (Ser46), Bax, cleaved caspase-9, -3, cleavage of poly(ADP-ribose)polymerase
      (PARP) and a decrease in Bcl-2 levels. An augmentation in cell cycle checkpoint
      protein p21(Waf1/Cip1) was accompanied by a cell cycle arrest in S-phase. DNA
      fragmentation visualized by the comet assay and the number of apoptotic cells
      increased time dependently as determined by flow cytometric annexinV and PI
      staining assays. In vivo, JMR-132 decreased the volume of HT-29, HCT-116 and HCT
      15 tumors xenografted into athymic mice up to 75% (p < 0.05) and extended tumor
      doubling time (p < 0.001). Our observations suggest that GHRH antagonist JMR-132
      exerts its antiproliferative effect on experimental colon cancer cells through
      p21(Waf1/Cip1) mediated S-phase arrest along with apoptosis involving the
      intrinsic pathway.

PMID- 19755850
TI  - A novel method to assess the full genome methylation profile using monoclonal
      antibody combined with the high throughput based microarray approach.
AB  - In this work we demonstrate a novel method of methylation detection that utilises
      immunoaffinity to detect the presence of methylated DNA hybridised to a cDNA
      microarray. We use a monoclonal antibody specific to 5 methyl cytidine to detect
      the presence of 5 methyl cytosine in genomic DNA from human fibroblasts bearing
      the karyotype 45 XO. We report that over 2,900 genes show the presence of
      methylation in this condition. We also report that 165 genes are consistently
      methylated in all replicates of these experiments. The methylated genes show a
      uniform distribution over all the chromosomes. The gene ontology of these also
      indicates no functional correlation between the genes that are methylated. We
      detect the presence of methylation in IGF2, an imprinted gene and thus known to
      harbour DNA methylation. The method is extremely specific and offers a quick and
      efficient way to analyse the methylation landscape on a high throughput scale.
      This method uses existing technology to assess methylation and thus can integrate
      very efficiently into any platform used.

PMID- 19755851
TI  - Ba2+ currents in inner and outer hair cells of mice lacking the voltage-dependent
      Ca2+ channel subunits beta3 or beta4.
AB  - Voltage-activated Ca(2+) channels comprise complexes of a pore-forming
      Ca(V)alpha(1) and auxiliary subunits Ca(V)beta, Ca(V)alpha(2)delta and sometimes
      Ca(V)gamma. The intracellular Ca(V)beta subunit assists in trafficking and
      surface expression of the Ca(V)alpha(1) subunit and can modulate biophysical
      properties of the Ca(2+) channel. Four genes, Ca(V)beta1-4, exist which confer
      different properties to Ca(2+) currents through the various Ca(V)alpha(1)
      subunits. Ca(2+) currents in cochlear inner (IHC) and outer hair cells (OHC)
      serving synaptic transmission flow predominantly through the L-type Ca(V)alpha(1)
      subunit Ca(V)1.3, but associated Ca(V)beta subunits are unknown. In the organ of
      Corti, we found mRNA and protein for all four Ca(V)beta subunits including
      Ca(V)beta2, but clear assignment of the Ca(V)beta1-4 immunolabelling with hair
      cells or nerve fibers was difficult. We analyzed Ca(V)beta3 knockout (Ca(V)beta3(
      /-)) and Ca(V)beta4 mutant mice (Ca(V)beta4(lh/lh)), which had normal hearing.
      Recording voltage-activated Ba(2+) currents from hair cells of the two mouse
      models revealed distinct significant changes of cell size and Ba(2+) current
      properties compared with their wild-type controls. Neonatal Ca(V)beta4(lh/lh)
      IHCs showed reduced membrane capacitances and changes in the voltage dependence
      and kinetics of current activation, whereas mature IHCs had reduced peak currents
      compared with Ca(V)beta4(wt), altogether indicating the presence of Ca(V)beta4 in
      IHCs. Ba(2+) currents of Ca(V)beta3(-/-) OHCs showed largely reduced amplitudes,
      changes in the voltage dependence and kinetics of Ba(2+) current activation, and
      increased inactivation compared with Ca(V)beta3(wt), pointing to a role of
      Ca(V)beta3 for OHCs. These results indicate that neither Ca(V)beta3 nor
      Ca(V)beta4 are indispensable for hair cell Ca(2+) currents but contribute to the
      overall current properties.

PMID- 19755852
TI  - The p53 tumor suppressor protein is a critical regulator of hematopoietic stem
      cell behavior.
AB  - In response to diverse stresses, the tumor suppressor p53 differentially
      regulates its target genes, variably inducing cell-cycle arrest, apoptosis or
      senescence. Emerging evidence indicates that p53 plays an important role in
      regulating hematopoietic stem cell (HSC) quiescence, self-renewal, apoptosis and
      aging. The p53 pathway is activated by DNA damage, defects in ribosome
      biogenesis, oxidative stress and oncogene induced p19 ARF upregulation. We
      present an overview of the current state of knowledge about p53 (and its target
      genes) in regulating HSC behavior, with the hope that understanding the molecular
      mechanisms that control p53 activity in HSCs and how p53 mutations affect its
      role in these events may facilitate the development of therapeutic strategies for
      eliminating leukemia (and cancer) propagating cells.

PMID- 19755853
TI  - Mitochondrial acetylcarnitine provides acetyl groups for nuclear histone
      acetylation.
AB  - Dynamic acetylation and deacetylation of nuclear histones is essential for
      regulating the access of chromosomal DNA to transcriptional machinery. The source
      of acetyl-CoA for histone acetylation in mammalian cell nuclei is not clearly
      known. We show that acetylcarnitine formed in mitochondria, is transported into
      cytosol by carnitine/acylcarnitine translocase, and then enters nucleus, where it
      is converted to acetyl-CoA by a nuclear carnitine acetyltransferase and becomes a
      source of acetyl groups for histone acetylation. Genetic deficiency of the
      translocase markedly reduced the mitochondrial acetylcarnitine dependent nuclear
      histone acetylation, indicating the significance of the carnitine-dependent
      mitochondrial acetyl group contribution to histone acetylation.

PMID- 19755854
TI  - Local and systemic antitumor effect of intratumoral and peritumoral IL-12
      electrogene therapy on murine sarcoma.
AB  - Soft tissue sarcomas pose a challenge for successful treatment with conventional
      therapeutic methods, therefore newer therapeutic approaches are considered. In
      this study, we evaluated the antitumor effect of IL-12 electrogene therapy (EGT)
      on murine SA-1 fibrosarcoma. The therapeutic plasmid was injected either
      intratumorally into subcutaneous SA-1 nodules or intradermally into the
      peritumoral region. We achieved a remarkable local and systemic antitumor effect
      with both approaches after single plasmid DNA application, with significant
      intratumoral and systemic production of IL-12 and IFNgamma. Intratumoral IL-12
      EGT resulted in over 90% complete response rate of the treated tumors with 60% of
      cured mice being resistant to challenge with SA-1 tumor cells. Peritumoral EGT
      resulted in a lower complete response rate (16%), with significant growth delay
      of remaining tumors. Both therapies also resulted in significant inhibition of
      growth of untreated tumors, growing simultaneously at a distant site. These data
      suggest that IL-12 EGT may be useful in the treatment of soft tissue sarcomas,
      exerting a local and systemic antitumor effect.

PMID- 19755855
TI  - Amplification of chromosomal segment 4q12 in non-small cell lung cancer.
AB  - In cancer, proto-oncogenes are often altered by genomic amplification. Here we
      report recurrent focal amplifications of chromosomal segment 4q12 overlapping the
      proto-oncogenes PDGFRA and KIT in non-small cell lung cancer (NSCLC). Single
      nucleotide polymorphism (SNP) array and fluorescent in situ hybridization (FISH)
      analysis indicate that 4q12 is amplified in 3-7% of lung adenocarcinomas and 8
      10% of lung squamous cell carcinomas. In addition, we demonstrate that the NSCLC
      cell line NCI-H1703 exhibits focal amplification of PDGFRA and is dependent on
      PDGFRalpha activity for cell growth. Treatment of NCI-H1703 cells with PDGFRA
      specific shRNAs or with the PDGFRalpha/KIT small molecule inhibitors imatinib or
      sunitinib leads to cell growth inhibition. However, these observations do not
      extend to NSCLC cell lines with lower-amplitude and broader gains of chromosome
      4q. Together these observations implicate PDGFRA and KIT as potential oncogenes
      in NSCLC, but further study is needed to define the specific characteristics of
      those tumors that could respond to PDGFRalpha/KIT inhibitors.

PMID- 19755856
TI  - Exploiting synthetic lethal interactions for targeted cancer therapy.
AB  - Emerging data suggests that synthetic lethal interactions between mutated
      oncogenes/tumor suppressor genes and molecules involved in DNA damage signaling
      and repair can be therapeutically exploited to preferentially kill tumor cells.
      In this review, we discuss the concept of synthetic lethality, and describe
      several recent examples in which this concept was successfully implemented to
      target tumor cells in culture, in mouse models, and in human cancer patients.

PMID- 19755857
TI  - DNA damage responses by human ELG1 in S phase are important to maintain genomic
      integrity.
AB  - Genomic integrity depends on DNA replication, recombination and repair,
      particularly in S phase. We demonstrate that a human homologue of yeast Elg1
      plays an important role in S phase to preserve genomic stability. The level of
      ELG1 is induced during recovery from a variety of DNA damage. In response to DNA
      damage, ELG1 forms distinct foci at stalled DNA replication forks that are
      different from DNA double strand break foci. Targeted gene knockdown of ELG1
      resulted in spontaneous foci formation of gamma-H2AX, 53BP1 and phosphorylated
      ATM that mark chromosomal breaks. Abnormal chromosomes including fusions,
      inversions and hypersensitivity to DNA damaging agents were also observed in
      cells expressing low level of ELG1 by targeted gene knockdown. Knockdown of ELG1
      by siRNA reduced homologous recombination frequency in the I-SceI induced double
      strand break-dependent assay. In contrast, spontaneous homologous recombination
      frequency and sister chromatin exchange rate were upregulated when ELG1 was
      silenced by shRNA. Taken together, we propose that ELG1 would be a new member of
      proteins involved in maintenance of genomic integrity.

PMID- 19755858
TI  - Inflammatory breast cancer cells are constitutively adapted to hypoxia.
AB  - We recently showed that overexpression of translation initiation factor eIF4G
      partially drives the unusual pathological features of Inflammatory Breast Cancer
      (IBC), the most lethal form of primary breast cancer. IBC has the peculiar
      feature that, rather than develop as a solid tumor, it typically generates
      rapidly metastasizing tight clusters of cancer cells referred to as tumor cell
      emboli, consisting of cancer cells held together by increased membrane expression
      of E-cadherin. Overexpression of eIF4GI in IBC leads to a specific increase in
      the translation of internal ribosomal entry site (IRES) containing mRNAs, of
      which two encode key proteins involved in the pathological features of IBC. One
      of these mRNAs encodes p120 catenin, which mediates E-cadherin retention at the
      cell surface, and the other encodes VEGF, which accounts for high levels of IBC
      angiogenesis and resistance to hypoxia. Here we show that IBC cells have adapted
      to the persistent hypoxia they experience as tumor emboli, by reprogramming the
      protein synthesis machinery to constitutively translate mRNAs required for IBC
      cell survival during hypoxia, even under normal oxygen (normoxic) conditions.
      Thus, IBC cells have been able to behave as if they are continuously hypoxic even
      when they are not.

PMID- 19755859
TI  - Activity and calcium regulate nuclear targeting of the calcium channel beta4b
      subunit in nerve and muscle cells.
AB  - Auxiliary beta subunits are critical determinants of membrane expression and
      gating properties of voltage-gated calcium channels. Mutations in the beta(4)
      subunit gene cause ataxia and epilepsy. However, the specific function of beta(4)
      in neurons and its causal relation to neurological diseases are unknown. Here we
      report the localization of the beta(4) subunit in the nuclei of cerebellar
      granule and Purkinje cells. beta(4b) was the only beta isoform showing nuclear
      targeting when expressed in neurons and skeletal myotubes. Its specific nuclear
      targeting property was mapped to an N-terminal double-arginine motif, which was
      necessary and sufficient for targeting beta subunits into the nucleus.
      Spontaneous electrical activity and calcium influx negatively regulated beta(4b)
      nuclear localization by a CRM-1-dependent nuclear export mechanism. The activity
      dependent shuttling of beta(4b) into and out of the nucleus indicates a specific
      role of this beta subunit in neurons, in communicating the activity of calcium
      channels to the nucleus.

PMID- 19755860
TI  - A CAAX motif can compensate for the PH domain of Num1 for cortical dynein
      attachment.
AB  - During mitosis in budding yeast, cortically anchored dynein exerts pulling forces
      on cytoplasmic microtubules, moving the mitotic spindle into the mother-bud neck.
      Anchoring of dynein requires the cortical patch protein Num1, which is
      hypothesized to interact with PI(4,5)P(2) via its C-terminal pleckstrin homology
      (PH) domain. Here we show that the PH domain and PI(4,5)P(2) are required for the
      cortical localization of Num1, but are not sufficient to mediate the cortical
      assembly of Num1 patches. A GFP fusion to the PH domain localizes to the cortex
      in foci containing approximately 2 molecules, whereas patches of full-length Num1
      GFP contain approximately 14 molecules. A membrane targeting sequence containing
      the CAAX motif from the yeast Ras2 protein can compensate for the PH domain to
      target Num1 to the plasma membrane as discrete patches. The CAAX-targeted Num1
      exhibits overlapping but largely distinct localization from wild-type Num1.
      However, it is fully functional in the dynein pathway. More importantly, cortical
      PI(4,5)P(2) is dispensable for the localization and function of the CAAX-targeted
      Num1. Together, these results demonstrate that cortical assembly of Num1 into
      functional dynein-anchoring patches is independent of its interaction with
      PI(4,5)P(2).

PMID- 19755861
TI  - The aurora B kinase inhibitor AZD1152 sensitizes cancer cells to fractionated
      irradiation and induces mitotic catastrophe.
AB  - AZD1152, an Aurora kinase inhibitor with selectivity for Aurora B kinase, can
      enhance the effect of ionizing radiation (IR). The aim of this study was to
      evaluate and to mechanistically explore scheduling effects of AZD1152 on tumor
      responses to IR, in three different settings: neoadjuvant (AZD1152 before IR),
      adjuvant (IR before AZD1152), or concomitant treatments (AZD1152 plus one single
      IR dose). A more pronounced tumor growth delay was observed in the neoadjuvant
      and adjuvant schedules as compared to the concomitant schedule. However, AZD1152
      enhanced the efficacy of IR when concomitant IR was fractionated over several
      days. Histopathological examination revealed that AZD1152 + IR induced
      polyploidy, multinucleation and micronuclei in vivo. Time-lapse videomicroscopy
      confirmed that cell death induced by AZD1152 + IR was preceded by multinucleation
      and the formation of micronuclei, which both are hallmarks of mitotic
      catastrophe. Caspase inhibition or removal of the pro-apoptotic protein Bax did
      not ameliorate the long-term cell survival of AZD1152-treated cancer cells. In
      contrast, a chemical inhibitor of CHK1, Chir124, sensitized cancer cells to the
      lethal effect of AZD1152. Altogether, these data support the contention that
      AZD1152 mediates radiosensitization in vivo by enhancing mitotic catastrophe,
      which can be used as a biomarker of treatment efficacy.

PMID- 19755862
TI  - Involvement of MKP-1 and Bcl-2 in acquired cisplatin resistance in ovarian cancer
      cells.
AB  - Although cisplatin is a very effective anticancer agent against several types of
      cancer including ovarian cancer, the mechanisms of acquired resistance are not
      fully understood. By chronically exposing cisplatin to ovarian cancer cell lines,
      we established two cisplatin-resistant cell lines OV433 and TOV112D. Our results
      indicate that the mechanisms underlying their cisplatin resistance are distinct.
      In OV433 cells, cisplatin resistance is associated with increased expression of
      mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1). By knocking down
      MKP-1 expression by siRNA or inhibiting MKP-1 expression by its pharmacological
      inhibitor triptolide, cisplatin-resistant OV433 cells became cisplatin-sensitive
      and subsequently increased cisplatin-induced apoptosis. In TOV112D cells, on the
      other hand, acquired cisplatin resistance is associated with increased levels of
      Bcl-2 protein. By inhibiting the activity of Bcl-2 protein with its
      pharmacological inhibitor gossypol or knocking down Bcl-2 expression by siRNA,
      cisplatin-resistant TOV112D cells became cisplatin-sensitive and subsequently
      increased cisplatin-induced apoptosis. Therefore, our data suggest that the
      mechanisms of acquired cisplatin resistance vary among ovarian cancer cells,
      which involve upregulation of molecules associated with the cell survival
      pathways.

PMID- 19755863
TI  - Molecular clustering of endometrial carcinoma based on estrogen-induced gene
      expression.
AB  - Identification of biomarkers potentially provides prognostic information that can
      help guide clinical decision-making. Given the relationship between estrogen
      exposure and endometrial cancer, especially low grade endometrioid carcinoma, we
      hypothesized that high expression of genes induced by estrogen would identify low
      risk endometrioid endometrial cancers. cDNA microarray and qRT-PCR verification
      were used to identify six genes that are highly induced by estrogen in the
      endometrium. These estrogen-induced biomarkers were quantified in 72 endometrial
      carcinomas by qRT-PCR. Unsupervised cluster analysis was performed, with
      expression data correlated to tumor characteristics. Time to recurrence by
      cluster was analyzed using the Kaplan-Meier method. A receiver operating
      characteristic (ROC) curve was generated to determine the potential clinical
      utility of the biomarker panel to predict prognosis. Expression of all genes was
      higher in endometrioid carcinomas compared to non-endometrioid carcinomas.
      Unsupervised cluster analysis revealed two distinct groups based on gene
      expression. The high expression cluster was characterized by lower age, higher
      BMI, and low grade endometrioid histology. The low expression cluster had a
      recurrence rate 4.35 times higher than the high expression cluster. ROC analysis
      allowed for the prediction of stage and grade with a false negative rate of 4.8%
      based on level of gene expression in endometrioid tumors. We have therefore
      identified a panel of estrogen-induced genes that have potential utility in
      predicting endometrial cancer stage and recurrence risk. This proof-of-concept
      study demonstrates that biomarker analysis may play a role in clinical decision
      making for the therapy of women with endometrial cancer.

PMID- 19755864
TI  - BED estimates of HIV incidence must be adjusted.

PMID- 19755865
TI  - Reply to 'Should biomarker estimates of HIV incidence be adjusted?'.

PMID- 19755866
TI  - BED estimates of HIV incidence must be adjusted.

PMID- 19755869
TI  - The state of the field: myology.

PMID- 19755870
TI  - Current world literature.

PMID- 19755872
TI  - Current world literature.

PMID- 19755876
TI  - Healthcare quality and disparities: attacking problems at their root.

PMID- 19755877
TI  - Person-centered care and organizational culture in long-term care.

PMID- 19755878
TI  - Nurses' responses to medication errors: suggestions for the development of
      organizational strategies to improve reporting.
AB  - The purpose of this study was to obtain a comprehensive understanding of how
      nurses respond to medication errors and identify strategies that nurses believe
      may improve reporting of these errors within hospitals. The findings suggest that
      nurses use a decision-making process when reporting medication errors. Medication
      error reporting may be improved by instituting a problem-solving approach to
      respectfully manage the event and providing nurses with clear guidelines,
      remedial education, and timely feedback.

PMID- 19755879
TI  - What does nursing teamwork look like? A qualitative study.
AB  - A qualitative study was conducted applying a theoretically based model of
      teamwork to determine relevant team processes among nurses. Nurses from 5 patient
      care units participated in focus groups, describing team processes in their daily
      work. Responses were analyzed in the Salas framework to develop a concrete
      conceptualization of teamwork within nursing teams. Results support the framework
      as a means for describing teamwork among nurses.

PMID- 19755880
TI  - Coordinating the roles of nursing home staff and families of elderly nursing home
      residents.
AB  - This study examines families' and nurses' perceptions of the functions that
      should be performed by families of elderly nursing home residents and whether
      there is congruency between nursing staff and families' perceptions. This was a
      quasi-experimental study and was based on questionnaires distributed among 85
      nurses and 68 families of nursing home residents. The findings indicated that the
      staff believes that families must assume more roles than the families think they
      should. In contrast, families believe that they should be more informed of the
      physical care of residents.

PMID- 19755881
TI  - Social capital and risk management in nursing.
AB  - The purpose of the study was to examine the relationship between social capital
      and clinical risk management in hospitals from nurses' perspective. The results
      of our investigation suggest that higher values of social capital are associated
      with better ratings in clinical risk management behavior. An established
      atmosphere of trust and a feeling of common values and convictions can help
      nurses integrate clinical risk management into their daily work.

PMID- 19755882
TI  - Nurses' perceptions of subspecialization in pediatric cardiac intensive care
      unit: quality and patient safety implications.
AB  - This study assessed the perceptions of nurses about the creation and staffing of
      a dedicated cardiac intensive care unit. Nurses perceived a clinical benefit to
      cohorting cardiac surgery patients; however, they reported more knowledge
      deficits in cardiac patient care than other intensive care unit disease
      categories. More than 25% of nurses reported a patient assignment in which they
      identified suboptimal skills to provide safe patient care. Years of clinical
      experience did not reduce concerns for quality of care or safe practice.

PMID- 19755883
TI  - Endnote...: it's only an infection.

PMID- 19755884
TI  - Conservative treatment of stable volar plate injuries of the proximal
      interphalangeal joint in children and adolescents: a prospective study.
AB  - OBJECTIVES: The purpose of this study was to assess a standard conservative
      management for stable volar plate injuries of the proximal interphalangeal joint
      in children and adolescents. No study is available regarding this subject for
      this age group. METHODS: A prospective study was performed on 37 consecutive
      patients (aged between 9 and 15 years; mean, 13 years) with stable acute volar
      plate injuries of the proximal interphalangeal joints, including 22 avulsion
      fractures without dislocation. All patients had a standardized conservative
      treatment consisting of a dorsal aluminum extension block splinting at a 15
      degree flexion for 10 days, followed by a spontaneous mobilization and taping to
      adjacent fingers for sports only. At follow-up visits, active and passive ranges
      of motion, swelling of the affected joints, analgesic intake, and pain perception
      by the patient were recorded. Regular follow-up consisted of standardized
      assessments at 2, 6, and 12 weeks, with additional consultations if symptoms
      persisted. RESULTS: Healing was uneventful, and hand therapy was not necessary to
      regain full range of motion in 32 of 33 children with a regular follow-up. The
      only flexion contracture observed responded well to splinting. Of the 33
      patients, 31 had an excellent outcome and 2 had a good outcome. CONCLUSIONS:
      Dorsal extension block splinting was an efficient, simple, well-tolerated
      treatment for stable volar plate injuries of the proximal interphalangeal joint
      in a preliminary series of patients younger 16 years. Flexion contractures were
      rare and responded well to dynamic splinting.

PMID- 19755885
TI  - Pediatric emergency medicine fellowship research curriculum: a survey of
      fellowship directors.
AB  - OBJECTIVE: To determine how pediatric emergency medicine (PEM) fellowship
      directors organize research training and to identify factors believed to be
      associated with successful research training. METHODS: A 16-question survey study
      of PEM fellowship directors. RESULTS: Of the 58 fellowship directors surveyed, 39
      (67%) responded. Of 38 programs, PEM faculty from 20 (53%) served as research
      mentors for PEM fellows. The mean percentage of PEM faculty who had performed
      peer-review funded research was 26%. The mean number of trainee research months
      was 10.9 for 3 years. Of these research months, 93% were not protected (included
      clinical work hours). Only 5 programs provided some completely protected research
      months (months without any clinical work hours), and none of these were scheduled
      in blocks of greater than 3 consecutive months. Most (56%) of these research
      months were scheduled during the third year of training. The most likely
      explanations of the fellow successfully becoming research competent were
      eagerness to apply self and number of research months during training. Least
      likely explanations were faculty with peer-reviewed funded grants and blocks of
      research time. Thirty-five fellowship directors (90%) believed that upon
      completion of the training, their fellows would be research competent.
      CONCLUSIONS: Besides the fellow's eagerness to apply self, scheduling adequate
      time for research was reported as a highly important factor in achieving research
      competency among PEM fellows. Providing protected (no clinical responsibilities)
      research months to fellows and arranging more opportunities for PEM faculty to
      serve as research mentors may maintain or possibly improve the likelihood of PEM
      fellows to becoming research competent.

PMID- 19755886
TI  - Intravenous contrast agents and associated changes in serum osmolality.
AB  - BACKGROUND: Anecdotal data suggest that intravenous contrast agents given to
      enhance the sensitivity of computed tomography (CT) can produce increases in
      serum osmolality, producing an osmolal gap. An unexplained osmolal gap often
      prompts extensive evaluation for the presence of unidentified toxins,
      particularly the toxic alcohols (methanol, ethanol, isopropyl alcohol, and
      ethylene glycol). The ability of intravenous contrast media to raise serum
      osmolality with a resulting osmolal gap has not been systematically investigated.
      METHODS: We evaluated changes in serum osmolality and osmolal gap in a cohort of
      patients presenting to a pediatric emergency department with abdominal pain who
      necessitated a contrast-enhanced CT scan as part of their diagnostic evaluation.
      Inclusion criteria were age of 10 to 18 years and the ability to obtain blood
      samples 30 minutes after contrast administration. Before and 30 minutes after
      contrast administration, serum osmolality and Na, glucose, and serum urea
      nitrogen levels were obtained. Osmolal gap was calculated using the formula 2(Na)
      + serum urea nitrogen/2.8 + glucose/18. The contrast agent Optiray 320 (Tyco
      healthcare, Mallinkrodt, Hazelwood, Mo) (ioversol, 68%) was administered at a
      dose of 2 mL/kg (1.36 g/kg). The main outcomes of interest were precontrast
      versus postcontrast osmolality and osmolar gap. RESULTS: Fourteen subjects were
      enrolled. The mean precontrast and postcontrast serum osmolalities were 292.75
      and 292.875 mOsm/L (P = 0.93), respectively. The corresponding mean values for
      the precontrast and postcontrast osmolal gaps were 9.17 and 12.15 mOsm/L,
      respectively (P = 0.133). The mean difference between the precontrast and the
      postcontrast osmolal gaps was 0.125 mOsm/L. There was no statistically
      significant correlation between the dose of the contrast agent administered and
      the postcontrast osmolality or osmolal gap. CONCLUSIONS: These data suggest that
      intravenous contrast agents, when administered at conventional doses, do not
      significantly increase serum osmolality or produce an osmolal gap. Patients who
      are found to have an osmolal gap after the performance of a contrast-enhanced CT
      scan should undergo thorough evaluation to identify its etiology rather than
      attributing the gap to contrast administration.

PMID- 19755887
TI  - Use of a discharge facilitator improves recall of emergency department discharge
      instructions for acute gastroenteritis.
AB  - OBJECTIVE: To determine whether the use of a bilingual discharge facilitator (DF)
      improves parental recall of discharge instructions in acute gastroenteritis in a
      pediatric emergency department (ED). METHODS: A nonrandomized educational
      intervention study with a historical control was conducted in a tertiary
      children's hospital between January 2004 and November 2004. English- or Spanish
      speaking parents of patients aged 3 months to 18 years with conditions diagnosed
      as acute gastroenteritis were eligible. The standard discharge group received
      written discharge instructions and standard ED discharge protocols. The
      intervention group received the written discharge instructions reinforced
      verbally by the DF in the parent's language of choice. Recall of 7 warning signs
      and symptoms was assessed 24 to 48 hours after the ED visit for both groups.
      RESULTS: For the English-speaking subgroup, a mean of 3.5 (95% confidence
      interval [CI], 3.26-3.78) signs or symptoms was identified correctly by 71
      subjects in the standard discharge group, and a mean of 4.1 (95% CI, 3.83-4.43)
      signs or symptoms was identified correctly by 94 subjects in the DF group. For
      the Spanish-speaking subgroup, a mean of 3.0 (95% CI, 2.67-3.36) signs or
      symptoms was identified correctly by 62 subjects in the standard discharge group,
      and a mean of 4.5 (95% CI 4.18-4.88) signs or symptoms was identified correctly
      by 64 subjects in the DF group. The differences remained significant after
      adjusting for patient age and the highest level of education attained by the
      parent. CONCLUSIONS: Verbal reinforcement of written discharge instructions by a
      bilingual DF improves parental recall of discharge instructions for
      gastroenteritis.

PMID- 19755888
TI  - Effectiveness of fever education in a pediatric emergency department.
AB  - OBJECTIVE: This study was designed to assess the impact of a brief educational
      video shown to parents during an emergency department visit for minor febrile
      illnesses. We hypothesized that a video about home management of fever would
      reduce medically unnecessary return emergency department visits for future
      febrile episodes. METHODS: A convenience sample of 280 caregivers presenting to
      one urban pediatric emergency department was enrolled in this prospective,
      randomized cohort study. All the caregivers presented with a child aged 3 to 36
      months with complaint of fever and were independently triaged as nonemergent. A
      pretest and posttest were administered to assess baseline knowledge and attitudes
      about fever. One hundred forty subjects were randomized to view either an 11
      minute video about home management of fever or a control video about child
      safety. Subjects were tracked prospectively, and all return visits for fever
      complaints were independently reviewed by 3 pediatric emergency physicians to
      determine medical necessity. RESULTS: There were no differences between the fever
      video and the control groups in baseline demographics (eg, demographically
      comparable). The fever video group had a significant improvement in several
      measures relating to knowledge and attitudes about childhood fever. There was no
      statistical difference between the intervention and control groups in subsequent
      return visits or in the determination of medical necessity. CONCLUSIONS: A brief
      standardized video about home management of fever improved caregiver knowledge of
      fever but did not decrease emergency department use or increase medical necessity
      for subsequent febrile episodes.

PMID- 19755889
TI  - Body mass index and pediatric asthma outcomes.
AB  - OBJECTIVE: The purpose of this study was to determine the association between
      body mass index (BMI), a measure of obesity, with emergency department admission
      rate in children with asthma. METHODS: This was a prospective study in a tertiary
      care, urban pediatric emergency department. Treating physicians and academic
      associates enrolled subjects during June 2005 to April 2008. Eligible subjects
      with documented weight and height were between ages 6 and 18 years with chief
      complaint of wheezing. We compared admission rates between overweight children
      (BMI, > or = 85% percentile) and nonoverweight children (BMI, < 85% percentile).
      Data were expressed as mean (SD). Group comparisons were made by Student t test
      or Fisher exact test, as appropriate. All tests were 2-tailed with an alpha set
      at 0.05. RESULT: We studied 183 children, where 108 children were classified
      overweight. Demographic differences (mean age, male sex, and African-American
      race) between overweight and nonoverweight children were not statistically
      significant. In addition, changes in asthma outcome measures (inpatient
      admissions during the previous year, asthma visits in the last 30 days, and
      missed school days in the last 30 days) were not statistically significant. Only
      household tobacco use approached statistical significance (P = 0.07). The
      admission rate for nonoverweight children was 9.3% (95% confidence interval [CI],
      4.3-18.3) compared with the 10.2% (95% CI, 5.6-17.5) for overweight children; a P
      = 1.0 was equivalent. CONCLUSIONS: Body mass index, a method to quantify
      overweight children, failed to predict admission of children with ambulatory
      asthma who presented to the pediatric emergency department.

PMID- 19755890
TI  - Characteristics of pediatric trauma in an urban city in Japan.
AB  - OBJECTIVES: To clarify the characteristics of recent pediatric injuries in an
      urban city in Japan. METHODS: Any patient who was under 13 years old and admitted
      for treatment of trauma between January 2000 and December 2007 was
      retrospectively investigated. The subjects were divided into 2 groups, the head
      injury (HI) and the control groups. The HI group had an abbreviated injury score
      (AIS) of the head greater than 1, and the control group had an AIS of the head
      equal to 0 or 1. RESULTS: The number of patients in the HI group was 95; and in
      the control group, 74. There were no penetrating injuries. The proportion of
      patients who were run over in the HI group was smaller than that in the control
      group. The injury severity score in the HI group was greater than that in the
      control group. The abdominal AIS in the HI group was smaller than that in the
      control group. The number of extracranial injuries (sum of all AIS except for the
      head) in the HI group was smaller than that in the control group. The survival
      rate in the HI group was smaller than that in the control group. All causes of
      death in the HI group were cerebral complications. CONCLUSIONS: The severity and
      outcome of pediatric blunt traumas were dependent on HI. Because the extracranial
      injuries with an HI were not severe, the successful treatment of the cerebral
      complications could lead to favorable outcome.

PMID- 19755891
TI  - Observation option for acute otitis media in the emergency department.
AB  - OBJECTIVES: The objective of our study was to evaluate the efficacy of the
      observation option for the treatment of acute otitis media (AOM) in the emergency
      department (ED). METHODS: The study was designed as a prospective case series. It
      was conducted in a suburban academic emergency department, with pediatric
      patients 2 years or older as participants. INTERVENTIONS AND OUTCOMES: The
      patient population consisted of children 2 years or older with conditions
      diagnosed as AOM. Patients were excluded if they had a history of any potentially
      immunocompromising conditions or a history of recurrent AOM. Patients were
      treated with ibuprofen or acetaminophen in the ED. The parents were given a
      prescription for antibiotics but were asked not to fill the prescription
      immediately. Parents were contacted by phone for follow-up. RESULTS: One hundred
      forty-four patients were enrolled in the study. One hundred five (73%) recovered
      uneventfully without ever requiring antibiotics. Thirty-nine patients were
      treated with antibiotics. Of the 39 patients who were started on antibiotics, 11
      patients had at least 1 episode of vomiting or diarrhea, and 5 of these patients
      had their antibiotic changed because of it. CONCLUSIONS: Our study demonstrates
      that the observation option as defined by the New York Otitis Project Committee
      can be safely implemented in the ED and prevented the administration of
      antibiotics in more than 70% of the patients in our group. This suggests that if
      the observation option became the standard of care for the treatment of AOM,
      antibiotic administration for this disease could be significantly reduced.

PMID- 19755892
TI  - Initial base deficit as predictors for mortality and transfusion requirement in
      the severe pediatric trauma except brain injury.
AB  - OBJECTIVE: The initial base deficit (BD) is an important indicator of shock in
      adult trauma patients, but its value is unclear in pediatric trauma patients.
      This study assessed the ability of the initial BD to predict mortality and blood
      transfusion requirements in children except severe brain injury patients.
      METHODS: This study was a retrospective review of pediatric patients with severe
      trauma arriving at the emergency department of a university hospital from January
      1998 to June 2005. Blood pressure, the initial BD, and the Injury Severity Score
      were assessed as independent predictors of mortality and the blood transfusion
      requirement using multiple regression analysis. RESULTS: The study group
      constituted 102 patients. According to the multiple regression analysis results,
      the initial systolic blood pressure, Injury Severity Score, and blood transfusion
      requirement were not independent predictors of mortality (P = 0.104, 0.959,
      0.386, respectively). By contrast, the initial BD was an independent predictor,
      with an odds ratio of 13.6 for BD of -8 mEq/L or less (confidence interval [CI],
      3.51-35.23, P = 0.037), and systolic blood pressure and BD were independent
      predictors of blood transfusion requirement; the odds ratio for hypotension was
      3.2 (CI, 0.51-8.32, P = 0.044), and the odds ratio was 15.3 for BD values of -8
      or less (CI, 2.24-51.43, P = 0.003). CONCLUSION: The initial BD in pediatric
      trauma patients except severe brain injury was an independent predictor of
      mortality and blood transfusion requirement within 24 hours. Mortality and blood
      transfusion requirement were significantly high when initial BD was less than -8
      mEq/L.

PMID- 19755893
TI  - Acute subdural hematoma: potential soccer injury in an otherwise healthy child.
AB  - A 16-year-old adolescent boy presented with headache, dizziness, loss of
      consciousness, and a tonic-clonic seizure after heading a soccer ball in a
      competitive match. A computed tomographic scan of the head revealed an acute
      subdural hematoma with a mass effect. The patient was emergently referred to a
      tertiary care facility where he eventually recovered completely with conservative
      care. No predisposing medical conditions were found. To the best of our
      knowledge, this is the first report of an intracranial hemorrhage secondary to
      the heading of a soccer ball alone in an otherwise healthy child without any
      underlying predisposing central nervous system abnormalities.

PMID- 19755894
TI  - Traumatic posterior dislocation of the hip in a 3-year-old child.
AB  - We report the case of a traumatic posterior dislocation of the hip in a 3-year
      old boy. After a fall in the garden, the boy was brought to our emergency
      department where an x-ray confirmed a posterior dislocation of his right hip. A
      successful prompt reduction was performed in the operating room under general
      anesthesia. This uncommon injury represents an orthopedic emergency and requires
      prompt reduction to lessen the risk of complications including avascular necrosis
      of the femoral head.

PMID- 19755895
TI  - Open-book pelvic fracture in late pregnancy.
AB  - Pelvic fractures in pregnancy are a relatively rare event. Special consideration
      needs to be considered when evaluating these patients. We present a case of a 15
      year-old pregnant teenager who was an unrestrained passenger in a motor vehicle
      collision who sustained an open-book pelvic fracture. Care of the patient
      requires a coordination of care between the patient and the fetus.

PMID- 19755896
TI  - Hypoventilation due to reinhalation in infants with a transport ventilator.
AB  - An infant of 5 kg of body weight was being ventilated with a conventional
      ventilator with a tidal volume of 40 mL and respiratory rate of 35 rpm,
      maintaining an expired CO2 of 37 mm Hg and a transcutaneous PCO2 of 43 mm Hg. For
      transfer, an Oxylog 3000 ventilator (Drager, Lubeck, Germany) was set to
      intermittent positive-pressure ventilation mode with a tidal volume of 50 mL and
      the same respiratory frequency. After connecting, the expired CO2 increased
      rapidly to 75 mm Hg; the inspired CO2, to 27 mm Hg; and the transcutaneous PCO2,
      to 82 mm Hg, despite good chest expansion. The respirator was checked and found
      to be correct. On changing to the conventional ventilator, a rapid decrease was
      found in the expired CO2 and transcutaneous PCO2 values and the inspired CO2 fell
      to 0. The Oxylog 3000 ventilator should not be used for the transport of small
      children because the dead space rise to a significant reinhalation in these
      patients. Capnography and transcutaneous PCO2 are useful for the early detection
      of hypercapnia and the dead space during the transfer of pediatric patients.

PMID- 19755897
TI  - Urinary tract infection in a healthy 10-year-old boy: an occult etiology.
AB  - We report a 10-year-old previously healthy boy who presented to our emergency
      department with a history of gross hematuria. Urinalysis was consistent with a
      urinary tract infection, an uncommon disease in healthy young boys. Further
      questioning revealed a history of self-instrumentation.

PMID- 19755898
TI  - An unusual cause of pediatric altered mental status: a mesenteric hernia.
AB  - Altered mental status can have many causes, some of which are life threatening,
      especially in children. In addition to the usual central nervous system and
      metabolic causes, such as meningitis, encephalitis, seizure, electrolyte
      imbalance, and inborn errors of metabolism, some less common causes of altered
      mental status, which if not diagnosed and managed rapidly, can have poor
      consequences. We present a case of a child with a life-threatening unusual cause
      of altered mental status, a mesenteric hernia with hypovolemic shock. The hernia
      was reduced successfully at laparotomy. The postoperative course was uneventful.

PMID- 19755899
TI  - Tarsometatarsal injury in a child.
AB  - Tarsometatarsal joint injuries are well described in adults. In children, these
      injuries have been less described and have been reported only as small case
      series. They frequently go unrecognized in children because of skeletal
      immaturity and lack of awareness among health care providers. However, these
      injuries if untreated can result in significant pain and deformity in children.
      It is important that treating physicians recognize the symptoms and signs of
      these injuries and initiate further diagnostic workup, especially when there is
      persistent foot pain in the absence of radiographic signs of a fracture. We
      present a case of an 11-month-old female infant who presented with foot pain
      after a fall.

PMID- 19755900
TI  - Chlamydia pneumonia mimicking miliary tuberculosis.
AB  - Chlamydia trachomatis is a common cause of subacute, afebrile pneumonia with
      onset from 1 to 3 months of age. On physical examination, crepitant inspiratory
      rales are commonly heard. Infiltration is usually bilateral and interstitial;
      reticulonodular pattern and atelectasis have also been described, which distinct
      the disease from miliary tuberculosis. We report an infant who had a disseminated
      miliary pattern in the chest radiograph and computed tomographic scan of the
      thorax that was diagnosed as Chlamydia pneumonia with serologic investigations.
      We emphasized that Chlamydia trachomatis can cause a miliary reticulonodular
      pattern in radiological examinations of infants who were admitted with
      respiratory symptoms. We suggest that pneumonia due to C. trachomatis should be
      kept in mind in the differential diagnosis of infants examined because of a
      diffuse miliary pattern.

PMID- 19755901
TI  - Early introduction of peritoneal dialysis may improve survival in severe sepsis.
AB  - OBJECTIVES: Acute renal failure is a serious complication of sepsis and is
      associated with a very high mortality. Recent evidence suggests that
      proinflammatory cytokines (interleukins 1 and 6 and tumor necrosis factor alpha)
      released into the circulation in response to sepsis can be removed from the blood
      via hemofiltration and appear in the dialysate in times of peritoneal dialysis as
      well. METHODS: An infant who developed acute renal failure in full-blown sepsis
      is presented. Peritoneal dialysis was initiated on the fourth day after
      admission. Changes in clinical and laboratory parameters were monitored. RESULTS:
      Urine output (1.13 mL/kg per hour) began to improve on the sixth day after
      admission (second day after the introduction of peritoneal dialysis);
      normalization of serum creatinine level was achieved on the 30th day after
      admission. Parallel with the serum creatinine level (255 micromol/L on day 5
      after admission vs 208 micromol/L by day 9 after admission, fifth day of PD),
      serum procalcitonin, C-reactive protein, and lactate dehydrogenase levels
      decreased dramatically (procalcitonin >500 vs 261 microg/L; C-reactive protein,
      203 vs 25.9 mg/L; and lactate dehydrogenase, 3092 vs 1744 U/L on days 5 and 9
      after admission, respectively). CONCLUSIONS: Considering that there are no
      guidelines defined for the management of acute renal failure with accompanying
      sepsis in children, authors point out that peritoneal dialysis is an easy-to
      perform and effective renal replacement modality in low body weight, critically
      ill patients. Early initiation of peritoneal dialysis does not only improve fluid
      and electrolyte imbalance but also may significantly reduce the destructive
      effect of systemic cytokine storm in sepsis and contribute to a more favorable
      outcome, even in cases of critical cardiovascular and hemostaseological status.

PMID- 19755902
TI  - Gridding: a form of folk medicine for respiratory illness.
AB  - Gridding and other folk remedies are commonly employed for respiratory illnesses.
      Pediatric health care providers need to be aware of such practices and their
      potential complications.

PMID- 19755903
TI  - Huffing and puffing to lose weight.

PMID- 19755904
TI  - Update on sexually transmitted infections, 2008.
AB  - Sexually transmitted infections (STIs) continue to be a great concern in the
      adolescent population and of particular concern to the pediatric emergency
      medicine physician. The Centers for Disease Control and Prevention reports that
      rates of gonorrheal and chlamydial infections are greatest in female adolescents,
      aged 15 to 19 years, and many people acquire human papilloma virus and human
      immunodeficiency virus infections during their teenage years. Adolescents
      continue to be at a higher risk for acquiring STIs because of multiple factors,
      including being more biologically susceptible, more likely to engage in
      unprotected sex with multiple partners, as well as facing various obstacles to
      their use of the health care system. The pediatric emergency medicine physician
      must be aware of the various presentations of STIs in their patients, as well as
      how to adequately treat and offer counseling to this vulnerable population.

PMID- 19755905
TI  - ECGs in the ED.

PMID- 19755906
TI  - Group A streptococcal infection observations.

PMID- 19755907
TI  - Recognition of "plastic bronchitis" in the emergency department.

PMID- 19755908
TI  - A revaluation of folliculosebaceous cystic hamartoma: the histopathological and
      immunohistochemical features.
AB  - The histogenesis of folliculosebaceous cystic hamartoma (FSCH), including the
      origin of the frequently associated adipocytes and other mesenchymal components,
      remains unclear. There are controversial problems regarding FSCH, such as the
      relationship between FSCH and trichofolliculoma (TF), and the exact concept of
      sebaceous TF. Fourteen FSCHs and 1 sebaceous TF were revaluated for the
      histopathology and studied for immunohistochemical profile of various
      cytokeratins, hair follicular stem cell markers, and others. The nestin
      expression was partly upregulated in the sebaceous duct structures and the
      proliferating spindle cells in the surrounding connective tissue in some lesions.
      S-100 protein staining clarified the presence of lipogenesis in these nestin
      expressed lesions, and the nestin-positive spindle cells were also seen around
      the immature adipocytes. Some FSCHs showed the focal follicular differentiation,
      where no signs of catagen or telogen stage were seen. One peculiar case showed
      both FSCH and TF features equally. The possibility that the adipocytes and other
      mesenchymal components in FSCHs originated from the nestin-positive multipotent
      stem cells was suggested. It is not convincing that FSCH and TF represent a
      chronological change in the spectrum of the same condition. Each FSCH and TF is
      therefore considered to be a distinctive entity. They may develop under a similar
      pathogenesis differing from each other in the direction of fundamental
      differentiation. In contrast to the TF lesions, the unusual upregulation of
      nestin expression is occasionally seen in FSCH lesions, including their stromas,
      which may thus result in the production of various kinds of mesenchymal
      components in FSCHs.

PMID- 19755909
TI  - Spiny projections on the palms and soles. Spiny keratoderma of the palms and
      soles.

PMID- 19755910
TI  - A histological examination for skin atrophy after 6 months of treatment with
      fluocinolone acetonide 0.01%, hydroquinone 4%, and tretinoin 0.05% cream.
AB  - Melasma is a common disorder affecting a significant percentage of the
      population, particularly those with skin of color. Therapy with hydroquinone, a
      depigmenting agent, as a single agent or in combination with other agents has
      been used with variable success. A triple-combination (TC) cream combining
      hydroquinone 4% with tretinoin 0.05% and fluocinolone acetonide 0.01% was
      developed for the treatment of melasma. We studied the use of TC cream for 24
      weeks and had tissue samples for all time points in 62 patients with moderate to
      severe melasma. The atrophogenic potential of TC cream was evaluated through
      serial histopathologic examination of skin biopsies. No statistically significant
      histopathologic signs of atrophy of the epidermis or dermis were noted at any
      time point throughout the study. There was a marked reduction in epidermal
      melanin in treated subjects; however, we did not observe any significant
      difference in baseline and treated samples in the amount of perivascular
      inflammatory infiltrate, dermal mucin, keratinocyte and melanocyte atypia, or
      mast cells, consistent with findings of previous studies where topical retinoids
      were used. An increase in the mean number of blood vessels per square millimeter
      of tissue was observed in 2 study cohorts between baseline and week 24. These
      results suggest that the risk of skin atrophy with 24-week use of TC cream for
      the treatment of melasma is very low.

PMID- 19755911
TI  - Mask-like metastasis: report of 2 cases of 4 eyelid metastases and review of the
      literature.
AB  - Bilateral periorbital edema and swelling are frequent in clinical practice and
      are commonly attributed to orbital contact dermatitis due to different drugs and
      cosmetic products. However, when there is a background of a solid cancer, the
      possibility of eyelid metastasis should be also considered. Metastases to the
      eyelids are rare, and in most cases, these lesions are unilateral. Because only a
      few cases of bilateral involvement have been reported in the literature, clinical
      and morphological data of this variant are under recognized. We report the
      clinical and histopathological characteristics of 2 patients with 4 eyelid
      metastasis and review the previous cases reported in the literature.

PMID- 19755912
TI  - Altered standards of care during an influenza pandemic: identifying ethical,
      legal, and practical principles to guide decision making.
AB  - Although widespread support favors prospective planning for altered standards of
      care during mass casualty events, the literature includes few, if any, accounts
      of groups that have formally addressed the overarching policy considerations at
      the state level. We describe the planning process undertaken by public health
      officials in the Commonwealth of Massachusetts, along with community and academic
      partners, to explore the issues surrounding altered standards of care in the
      event of pandemic influenza. Throughout 2006, the Massachusetts Department of
      Public Health and the Harvard School of Public Health Center for Public Health
      Preparedness jointly convened a working group comprising ethicists, lawyers,
      clinicians, and local and state public health officials to consider issues such
      as allocation of antiviral medications, prioritization of critical care, and
      state seizure of private assets. Community stakeholders were also engaged in the
      process through facilitated discussion of case scenarios focused on these and
      other issues. The objective of this initiative was to establish a framework and
      some fundamental principles that would subsequently guide the process of
      establishing specific altered standards of care protocols. The group collectively
      identified 4 goals and 7 principles to guide the equitable allocation of limited
      resources and establishment of altered standards of care protocols. Reviewing and
      analyzing this process to date may serve as a resource for other states.

PMID- 19755913
TI  - Virologic response differences between African Americans and European Americans
      initiating highly active antiretroviral therapy with equal access to care.
AB  - OBJECTIVE: Studies comparing virologic response to highly active antiretroviral
      therapy (HAART) between African Americans (AA) and European Americans (EA) have
      been confounded by differences in duration of HIV infection and access to health
      care. We evaluated virologic response to HAART between ethnicities in a large
      cohort with fewer confounders. METHODS: The odds of attaining viral suppression
      at 6- and 12-months post-HAART were determined by multivariate logistic
      regression for HIV-infected AA and EA prospectively followed in a large US
      military cohort. Time-to-event methods were used to compare maintenance of
      suppression. RESULTS: A total of 1363 subjects (51% AA, 92% men) with viral load
      results available 6 months after HAART initiation were included. There was no
      difference between ethnicities in time from seroconversion to HIV diagnosis or
      HAART initiation or in HAART regimens. Adjusted for multiple demographic and HIV
      related factors, AA had significantly lower odds of obtaining undetectable viral
      loads after 6 (odds ratio 0.6, 95% confidence interval 0.4-0.8, P < 0.001) and 12
      months (odds ratio 0.6, 95% confidence interval 0.4-0.8, P = 0.002) of HAART.
      Once undetectable, there was no difference in time to virologic failure between
      AA and EA. CONCLUSIONS: Despite similar durations of HIV infection and equal
      access to health care, AAs were significantly less likely to achieve viral
      suppression compared with EA.

PMID- 19755914
TI  - Characteristics associated with retention among African American and Latino
      adolescent HIV-positive men: results from the outreach, care, and prevention to
      engage HIV-seropositive young MSM of color special project of national
      significance initiative.
AB  - BACKGROUND: Surveillance points to an urgent public health need for HIV
      prevention, access, and retention among young men of color who have sex with men
      (YMSM). The purpose of this multisite study was to evaluate the association
      between organizational- and individual-level characteristics and retention in HIV
      care among HIV-positive YMSM of color. METHODS: Data were collected quarterly via
      face-to-face interviews and chart abstraction between June 2006 and September
      2008. Participants were aged 16-24 years, enrolled at 1 of 8 participating youth
      specific demonstration sites, and engaged or reengaged in HIV care within the
      last 30 days. Generalized estimating equations were used to examine factors
      associated with missing research and care visits. Stata v.9.0se was used for
      analysis. RESULTS: Of 224 participants, the majority were African American
      (72.7%), 19-22 years old (66.5%), had graduated high school or equivalent
      (71.8%), identified as gay or homosexual (80.8%), and disclosed having had sex
      with a man before HIV diagnosis (98.2%). Over the first 2(1/4) years of the
      study, only 11.4% of visits were missed without explanation or patient contact.
      Characteristics associated with retention included being <21 years old, a history
      of depression, receipt of program services, and feeling respected at clinic;
      those associated with poorer retention included having a CD4 count <200 at
      baseline and being Latino. CONCLUSIONS: Special Projects of National Significance
      programs were able to achieve a high level of retention over time, and individual
      and program characteristics were associated with retention. Latino YMSM, those
      not receiving services, and those not perceiving respect at the clinic were at
      increased risk of falling out of care. Retention is essential to providing HIV+
      adolescents with treatment, including reducing antiretroviral resistance
      development. Innovative programs that address the needs of the YMSM of color
      population may result in improved retention.

PMID- 19755915
TI  - Atorvastatin restores the impaired vascular endothelium-dependent relaxations
      mediated by nitric oxide and endothelium-derived hyperpolarizing factors but not
      hypotension in sepsis.
AB  - Sepsis has been reported to impair endothelium-dependent vasodilations mediated
      by nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF).
      Although some studies demonstrate that statins can improve NO-mediated response
      in septic animals, little is known about its effect on the EDHF response. The
      present study examined the effects of atorvastatin pretreatment on sepsis-induced
      endothelial dysfunctions and hypotension in rats. Eighteen hours after the
      induction of sepsis by cecal ligation and puncture, thoracic aorta and second
      generation pulmonary arteries were isolated to examine acetylcholine-induced
      endothelium-dependent dilations mediated by NO and EDHF, respectively. The
      messenger RNA (mRNA) expression for endothelial NO synthase (eNOS) and inducible
      NO synthase (iNOS) was done by real-time polymerase chain reaction. NO was
      measured as nitrate/nitrite release using Griess method. Mean arterial pressure
      was measured by the invasive method. Sepsis significantly decreased (26%) the
      relaxation response to acetylcholine in the rat aorta. It also markedly inhibited
      the eNOS mRNA expression and acetylcholine-stimulated NO release in this vessel.
      Pretreatment of the rats with atorvastatin (10 mg/kg, orally) 48, 24, and 2 hours
      before induction of sepsis preserved acetylcholine-induced relaxation, eNOS mRNA
      expression, acetylcholine-stimulated NO release, and attenuated increase in the
      inducible NO synthase mRNA expression and basal NO production in the aorta. The
      maximal EDHF response mediated by acetylcholine was 25.30% +/- 3.00% in the
      pulmonary artery. Sepsis abolished this response but atorvastatin restored it
      (22.55% +/- 2.50%). Atorvastatin, however, failed to prevent sepsis-induced
      hypotension. These results suggest that atorvastatin can restore impaired
      endothelium-dependent vasodilations mediated by NO and EDHF but not hypotension
      in sepsis.

PMID- 19755916
TI  - Vitamin E supplementation and hepatic drug metabolism in humans.
AB  - Meta-analyses studies suggest that high-dose vitamin E may be associated with
      increased mortality in some populations. Vitamin E may increase the production of
      CYP3A4 in the liver, and this could lead to an increase in drug metabolism,
      potentially lowering the efficacy of therapeutic drugs. We hypothesized that
      upregulation of CYP3A4 by alpha-tocopherol (alpha-TOH) would decrease the plasma
      concentration of the CYP3A4 substrate midazolam. Baseline metabolism of midazolam
      (1 mg intravenously) was determined in 12 healthy subjects before randomization
      into 2 groups of 6 to receive either RRR-alpha-TOH (750 IU/d) or placebo for 3
      weeks. At completion, subjects were given an additional 1 mg intravenous bolus of
      midazolam. Plasma midazolam, 1-hydroxy-midazolam, and urinary alpha-TOH
      metabolite excretion were measured using gas chromatography mass spectrometry.
      Serum alpha-TOH was measured using high performance liquid chromatography with
      electrochemical detection. Serum alpha-TOH increased by 100% (P = 0.002) and
      urinary alpha-TOH metabolite excretion increased 20-fold in the treatment group
      versus placebo (P = 0.001). There was no effect on the area under time curve of
      midazolam in subjects taking alpha-TOH compared with placebo. These findings do
      not support the hypothesis that alpha-TOH supplementation interferes with hepatic
      CYP3A4-mediated drug metabolism.

PMID- 19755917
TI  - Angiotensin type 1 receptor expression and interleukin-8 production in
      polymorphonuclear leukocytes of patients with peripheral arterial disease.
AB  - We investigated angiotensin type 1 receptor (AT1R) expression and interleukin-8
      (IL-8) productions in polymorphonuclear leukocytes obtained from patients with
      peripheral arterial disease (PAD) undergoing femoral endarterectomy. Subjects at
      high cardiovascular risk (high-risk subjects, HRS) and healthy controls (HC) were
      also enrolled. To this end, patients with PAD were studied 1 month before
      surgery, at the time of surgery, and 3 and 6 months after surgery.
      Polymorphonuclear leukocytes were obtained from venous blood and evaluated for
      AT1R expression at messenger RNA (mRNA) and protein level and IL-8 production (by
      means of enzyme-linked immunosorbent assay). At baseline, AT1R membrane
      expression was similar in cells from patients with PAD, HRS, and HC, whereas AT1R
      mRNA was similar in patients with PAD and HC and higher in HRS. During the follow
      up period, AT1R expression progressively decreased both on the cell membrane and
      at the mRNA level. Both resting and stimulated production of IL-8 was lower in
      patients with PAD in comparison to HC and HRS and did not change during the
      follow up period. In PAD patients, femoral endarterectomy is associated with
      reduction of AT1R expression however with no apparent effect on IL-8 production.
      The relevance of such effects for cardiovascular protection deserves
      consideration.

PMID- 19755918
TI  - Concept of the vulnerable parameter: the Sicilian Gambit revisited.
AB  - Why consider the concept of the vulnerable parameter in a series on "Noninvasive
      Risk Assessment in Guiding Therapy for Prevention of Sudden Death?" Preceding
      that question might be, "what is the vulnerable parameter?" In the following
      pages, we shall review the history behind the concept of the vulnerable
      parameter, its evolution after its initial identification, where it stands today,
      and finally, why the vulnerable parameter is important to our consideration of
      risk factors.

PMID- 19755919
TI  - Postinfarct treatment with oxytocin improves cardiac function and remodeling via
      activating cell-survival signals and angiogenesis.
AB  - BACKGROUND: We investigated whether postinfarct treatment with oxytocin (OT)
      improves left ventricular (LV) function and remodeling via cardiac repair of
      myocardial ischemia-reperfusion injury. METHODS AND RESULTS: Experiments were
      performed with 30 minutes of coronary occlusion and 2 or 14 days of reperfusion
      rabbit model of myocardial infarction. LV function and remodeling were
      significantly improved in the OT group. The infarct size was significantly
      reduced in the OT group. The number of CD31-positive microvessels was increased
      significantly in the OT group. There were no Ki67-positive myocytes in either
      group. The expression of the OT receptor, phosphorylated (p)-Akt protein kinase,
      p-extracellular signal-regulated protein kinase, p-enodthelial NO synthase, p
      signal transducer and activator of transcription 3, vascular endothelial growth
      factor, B-cell lymphoma 2, and matrix metalloproteinase-1 (MMP-1) were markedly
      increased in the OT group days 2 and 14 post myocardial infarction. CONCLUSIONS:
      Postinfarct treatment with OT reduces myocardial infarct size and improves LV
      function and remodeling by activating OT receptors and prosurvival signals and by
      exerting antifibrotic and angiogenic effects through activation of MMP-1,
      endothelial NO synthase, and vascular endothelial growth factor. These findings
      provide new insight into therapeutic strategies for ischemic heart disease.

PMID- 19755920
TI  - Erdheim-Chester disease in childhood: a challenging diagnosis and treatment.
AB  - Erdheim-Chester disease is a rare, non-Langerhans systemic histiocytosis
      characterized by bilateral sclerosis of the metaphyseal regions of the long bones
      and infiltration in other organs. The histopathologic hallmark is defined by a
      mononuclear infiltrate of foamy histiocytes and rare pathognomonic Touton giant
      cells with extensive fibrosis. This condition is exceptional in children. We
      report here a case of Erdheim-Chester disease in a 10-year-old girl with
      retroperitoneal infiltration and bone involvement, for whom the diagnosis was
      only established after a 3-year course with multiple biopsies. It is also the
      first pediatric case successfully treated with interferon-alpha suggesting that
      interferon-alpha can be a safe and efficient first-line therapy for this disease
      in children.

PMID- 19755921
TI  - Sequential transplants for respective relapse of Hodgkin disease and
      hemophagocytic lymphohistiocytosis: a treatment dilemma.
AB  - The association of hemophagocytic lymphohistiocytosis (HLH) with Hodgkin disease
      (HD) seems to be uncommon. A 9-year-old boy, diagnosed with HD-HLH, received
      chemotherapy and remained in complete remission for 21 months. Then the patient
      received the first autologous transplant and unfortunately died due to multiorgan
      failure after the second allogeneic transplant because of sequentially respective
      relapse of HD and HLH. The recurrence of HLH with a high Epstein-Barr virus load
      but without relapse of HD in the patient suggests that Epstein-Barr virus may
      have a major pathogenetic role in the specific disorder HLH-HD. Detailed reports
      relating to HLH-HD were also reviewed.

PMID- 19755922
TI  - Spontaneous hematomyelia in a child with hemophilia A: a case report.
AB  - Hemorrhagic complications in patients with hemophilia have been occasionally
      reported in the spinal column and the spinal cord. Treatment is based on prompt
      replacement therapy as the occurrence and development of neurologic dysfunction
      are related to the length of time between the onset of symptoms and the factor
      replacement. We report case of a 7-year-old hemophilic boy who presented with
      flaccid paraparesis resulting from thoracic hematomyelia. The patient showed
      gradual improvement on medical management with cryoprecipitate infusions. This
      case calls attention to the need for prompt diagnosis of rarely reported spinal
      hematomyelia based on clinical manifestations and radiologic features and
      highlights its management options in patients with hemophilia.

PMID- 19755923
TI  - Mycoplasma pneumoniae infection associated with pancytopenia: a case report.
AB  - Immune hemolytic anemia is a rare condition in childhood. Cold agglutinins have
      been implicated in the etiology of the hemolysis and frequently observed during
      Mycoplasma pneumoniae infections. We present here a case of cold agglutinin
      related hemolytic anemia, thrombocytopenia, and leukopenia secondary to M.
      pneumoniae associated pneumonia. It is suggested that even though very rare, M.
      pneumoniae infection should be considered as the underlying disease in a patient
      presenting with pancytopenia.

PMID- 19755924
TI  - Anemia of acute infection in hospitalized children-no evidence of hemolysis.
AB  - The objective of the study is to examine the assumption that a process of
      hemolysis plays a role in anemia of acute infection in children. The study was
      comprised of febrile pediatric patients, who had a positive blood or urine
      culture. Complete blood count measures were compared between hospitalization and
      prehospitalization or posthospitalization values. Children admitted to the
      hospital for elective surgical procedures served as controls. Blood parameters of
      hemolysis were investigated in some of the patients. Of the 70 patients studied,
      49 (70%) were diagnosed with pyelonephritis and 21 (30%) had bacteremia. Mean (+/
      SD) hemoglobin (Hgb) on hospital admission was 10.9+/-1.27 g/L as compared with
      12.1+/-1.03 g/L of the controls, P<0.0001. Compared with normal-for-age Hgb
      values as a standard, 42 (60%) cases were identified as anemic. Compared with
      hospitalization values, Hgb and hematocrit (Hct) were significantly higher in
      prehospitalization or posthospitalization, whereas WBC values were significantly
      lower. All parameters of hemolysis, namely reticulocytes, bilirubin, lactate
      dehydrogenase (LDH), and haptoglobin, were normal. Bacteremia and pyelonephritis
      are accompanied by a significant drop in Hgb level. There is no evidence of
      hemolytic anemia in these patients.

PMID- 19755925
TI  - Efficacy differences of pemetrexed by histology in pretreated patients with stage
      IIIB/IV non-small cell lung cancer: review of results from an open-label
      randomized phase II study.
AB  - INTRODUCTION: Recent pivotal phase III studies in patients with advanced non
      small cell lung cancer (NSCLC) consistently showed greater survival benefit of
      pemetrexed in patients with nonsquamous cell carcinoma histology (nonsquamous
      histology) compared with those with squamous cell carcinoma histology (squamous
      histology). To confirm the efficacy differences of pemetrexed by histologic type,
      we conducted an additional subgroup analysis of data from a Japanese randomized
      phase II study evaluating the efficacy and safety of pemetrexed 500 mg/m2 (P500)
      and 1000 mg/m2 (P1000) in patients with advanced NSCLC previously treated with
      chemotherapy. The efficacy and safety results of original phase II study have
      already been reported (Ohe et al., Clin Cancer Res 2008;14:4206-4212). METHODS:
      Objective response rates (ORRs), overall survival time, and progression-free
      survival time were analyzed by subgroup of histology, squamous, and nonsquamous,
      for the dose groups combined and separately. RESULTS: A total of 216 patients
      were evaluable for efficacy. One hundred sixty-eight patients had nonsquamous and
      48 had squamous histology. ORRs were 20.8% and 2.1% (p < 0.001); median survival
      times (MST) were 16.0 and 8.5 months (p < 0.001); and median progression-free
      survival times (PFS) were 3.1 and 1.6 months (p < 0.001) for nonsquamous and
      squamous histology, respectively. In patients who were randomized to the P500
      group, ORR were 23.5% and 0% (p = 0.0062); MST were 19.4 and 7.9 months (p <
      0.001); and PFS were 3.1 and 1.4 months (p < 0.001) for nonsquamous and squamous
      histology, respectively. In patients who were randomized to the P1000 group, ORR
      were 18.1% and 4.0% (p = 0.1113); MST were 13.5 months and 8.6 months (p =
      0.0971); and PFS were 3.1 and 1.7 months (p = 0.0024) for nonsquamous and
      squamous histology, respectively. There were no clinically relevant differences
      in the incidence of toxicities between histology groups. CONCLUSIONS: This study
      showed the difference of pemetrexed efficacy by histologic type, and this result
      supports the treatment-by-histology effect observed in the past pivotal phase III
      studies. Higher dose of pemetrexed resulted in similar outcomes both in patients
      with nonsquamous histology and squamous histology. Pemetrexed is not as effective
      as alternative therapies for previously treated squamous histology; however,
      pemetrexed should be the key agent for the treatment of patients with nonsquamous
      histology.

PMID- 19755926
TI  - Kawasaki disease after vaccination: reports to the vaccine adverse event
      reporting system 1990-2007.
AB  - BACKGROUND: Kawasaki disease (KD) is a multisystemic vasculitis primarily
      affecting children<5 years. A review of RotaTeq (rotavirus vaccine live) clinical
      trial data revealed higher, though not statistically significantly, KD rates
      among RotaTeq vaccines than placebo recipients. In June 2007, the RotaTeq label
      was revised accordingly. OBJECTIVES: To describe and assess KD reported to
      Vaccine Adverse Event Reporting System (VAERS) for all US licensed vaccines.
      METHODS: We reviewed all KD reports received by VAERS from 1990 through mid
      October 2007. Cases were characterized by age, gender, onset interval, and
      vaccine type. Proportional reporting ratio (PRR) was used to evaluate KD
      reporting for each vaccine compared with all others. Reporting rates were
      calculated using number of doses distributed as denominator. RESULTS: Through
      October 14, 2007, 107 KD reports were received by VAERS: 26 were categorized as
      classic cases, 19 atypical, 52 possible, and 10 were noncases. Of the 97 cases,
      91% were children<5 years. There was no clustering of onset intervals after day 1
      postvaccination. Before the RotaTeq label revision, the KD PRR was elevated only
      for Pediarix (DTaP, hepB, and IPV combined) but the KD reporting rate for
      Pediarix (0.59/100,000 person-years) was much lower than the background incidence
      rate (9-19/100,000 person-years) for children<5 years in the United States. After
      the revision, reporting of KD for RotaTeq was stimulated but the reporting rate
      for RotaTeq (1.47/100,000 person-years) was still much lower than the background
      rate. CONCLUSIONS: Our review does not suggest an elevated KD risk for RotaTeq or
      other vaccines. Continued postmarketing monitoring for KD is ongoing.

PMID- 19755927
TI  - Acquisition of serum antibodies reactive with enterohemorrhagic Escherichia coli
      virulence-associated factors by healthy Brazilian children and adults.
AB  - BACKGROUND: Patients with hemorrhagic colitis or hemolytic uremic syndrome due to
      enterohemorrhagic Escherichia coli (EHEC) develop serum IgM and IgG response to
      lipopolysaccharide (LPS) and to virulence factors such as intimin. The small
      numbers of cases of diarrhea associated with EHEC strains in Brazil suggests a
      pre-existing immunity probably due to previous contact with diarrheagenic E.
      coli. Our aim was to evaluate the development of the serum antibody repertoire to
      EHEC virulence factors in Brazilian children and adults. METHODS: Serum IgM and
      IgG antibodies were determined by enzyme-linked immunosorbent assay with LPS
      O111, LPS O26, and LPS O157 in 101 children between 2 months and 10 years of age
      and in 100 adult sera, by immunoblotting with protein membrane extracts and
      purified beta intimin; the ability of adult sera to neutralize Shiga toxin2 was
      also investigated. RESULTS: Children older than 24 months had IgM concentrations
      reactive with the 3 LPS equivalent to those seen in the adult group, and
      significantly higher than the group of younger children (P < 0.05). Anti-O26 and
      anti-O157 LPS IgG concentrations were equivalent between the 2 groups of children
      and were significantly different from the adult group (P < 0.05). The anti-O111
      LPS IgG levels in older children were intermediate between the younger group, and
      adults (P < 0.05). Immunoblotting revealed strong protein reactivity, including
      the conserved and variable regions of beta intimin and more than 50% of the adult
      samples neutralized Shiga toxin 2. CONCLUSIONS: Our results demonstrate an
      increasing anti-LPS and antiprotein antibody response with age, which could
      provide protection against EHEC infections.

PMID- 19755928
TI  - Early diagnosis of dengue virus infection by detection of dengue viral antigen in
      peripheral blood mononuclear cell.
AB  - BACKGROUND: An essential requirement related to treatment of dengue-infected
      patients is a rapid and accurate detection of dengue virus during febrile stage
      of the disease. OBJECTIVE: The study examined using direct immunofluorescence
      staining the presence of dengue viral antigen in peripheral blood mononuclear
      cells (PBMCs). METHODS: Four hundred forty-five blood samples from 164 patients
      with dengue fever, dengue hemorrhagic fever, and other febrile illnesses were
      collected daily from the day of admission until discharge and also at
      convalescent stage. Blood smear was stained with fluorescein isothiocyanate
      conjugated polyvalent dengue antiserum and examined under a fluorescent
      microscope. Dengue infection was confirmed by virus isolation and/or dengue
      specific IgM and IgG enzyme linked immunosorbent assay test. RESULTS: Dengue
      viral antigens were found in most PBMC samples of dengue infected patients
      collected on the day before defervescence and continued until 2 to 3 days
      afterward. The number of dengue viral antigen positive PBMCs was highest in
      patients with dengue shock syndrome. Sensitivity and specificity of this method
      during the febrile stage was 93.8% (95% confidence interval: 88.8%-98.9%) and
      100%, respectively. The positive and negative predictive values were 100% and
      69.0%, respectively. CONCLUSION: Detection of dengue viral antigen in direct PBMC
      smear provides a useful and rapid technique for early diagnosis of dengue virus
      infection.

PMID- 19755929
TI  - Human metapneumovirus associated with central nervous system infection in
      children.
AB  - BACKGROUND: Human metapneumovirus (hMPV) is an established pathogen of the
      respiratory tract of children and adults. hMPV is related to other
      paramyxoviruses known to cause encephalitis. Reports suggest that hMPV may cause
      disease of the central nervous system (CNS). METHODS: Two groups of patients were
      studied. The first group consisted of children between birth and 18 years from
      whom nasal scrapings were obtained between January 2004 and October 2005. hMPV
      RNA amplification by PCR was done and records were reviewed for clinical and
      demographic data. The second group consisted of patients with encephalitis
      referred to the California Encephalitis Project (CEP) for comprehensive
      diagnostic testing between November 2004 and June 2006. RESULTS: In group 1, 1474
      specimens were examined for hMPV RNA. Sixty-three evaluable patients were
      infected with hMPV of whom 4 (6.3%) had seizures, compared with 145 patients
      infected with RSV of whom 1 had seizures (0.7%, P = 0.031). Comparing respiratory
      syncytial virus (RSV) and hMPV infections, there was no significant difference in
      the occurrence of fever. All children with hMPV infections and seizures were
      hospitalized and 3 were intubated because of status epilepticus. Group 2
      consisted of 205 pediatric cases referred to CEP between November 2004 and June
      2006 who had hMPV testing done. hMPV was detected in nasopharyngeal swabs of 5
      patients. Neither hMPV RNA nor antihMPV specific IgM were detectable in the CSF
      from the 5 patients for whom CSF was available. CONCLUSION: Nine cases of CNS
      illness temporally associated with the presence of hMPV nucleic acid in the upper
      airway are described. Compared with children infected with RSV, children with
      hMPV were significantly more likely to have had a seizure. Our data, in
      conjunction with previously reported cases suggest that hMPV may be associated
      with a spectrum of CNS disease ranging from febrile seizures to severe, fatal
      encephalitis.

PMID- 19755930
TI  - Cellular immunity as a potential cause of local reactions to booster vaccination
      with diphtheria and tetanus toxoids and acellular pertussis antigens.
AB  - BACKGROUND: Booster doses of diphtheria-tetanus-acellular pertussis (DTaP)
      vaccines restore waning serum antibody values but frequently cause local
      inflammation. Cell-mediated immunity (CMI) develops after primary DTaP
      vaccination and might contribute to local reactions to booster doses, a
      possibility explored in this study. METHODS: Healthy 4 to 5-year-old children
      were bled before DTaP.IPV booster vaccination. Peripheral blood mononuclear cells
      were tested for proliferative responses to D toxoid (DT), T toxoid, pertussis
      toxoid, pertactin, filamentous hemagglutinin and fimbriae (FIM) types 2, 3, and
      cytokine release patterns assessed. Proliferative responses were examined in
      relation to prebooster serum antibody concentrations and local reaction rates,
      previously reported. RESULTS: Among 167 subjects tested, proliferative response
      rates were: filamentous hemagglutinin 95%, pertussis toxoid 90%, T toxoid 84%,
      pertactin 67%, DT 41%, and FIM 31%. Responses were present to 3 to 6 antigens in
      87% of subjects and absent altogether in 2%. Subjects without residual pertussis
      antibodies often had CMI to pertussis antigens. Subjects with CMI had higher
      corresponding serum antibody concentrations before the booster, compared with CMI
      negative subjects. CMI responses were mixed TH1/TH2 type by cytokine profile for
      all antigens. Injection site erythema (>or=5 mm) was twice as frequent in those
      with than without CMI to DT (P=0.009) or FIM (P=0.042, Fisher exact test), the
      only antigens evaluable. CONCLUSION: CMI to vaccine antigens was often detectable
      in children before preschool booster vaccination and preliminary evidence
      suggests a role for CMI in local reactions to this dose.

PMID- 19755931
TI  - A 3-D well-differentiated model of pediatric bronchial epithelium demonstrates
      unstimulated morphological differences between asthmatic and nonasthmatic cells.
AB  - There is a need for reproducible and effective models of pediatric bronchial
      epithelium to study disease states such as asthma. We aimed to develop,
      characterize, and differentiate an effective, an efficient, and a reliable three
      dimensional model of pediatric bronchial epithelium to test the hypothesis that
      children with asthma differ in their epithelial morphologic phenotype when
      compared with nonasthmatic children. Primary cell cultures from both asthmatic
      and nonasthmatic children were grown and differentiated at the air-liquid
      interface for 28 d. Tight junction formation, MUC5AC secretion, IL-8, IL-6,
      prostaglandin E2 production, and the percentage of goblet and ciliated cells in
      culture were assessed. Well-differentiated, multilayered, columnar epithelium
      containing both ciliated and goblet cells from asthmatic and nonasthmatic
      subjects were generated. All cultures demonstrated tight junction formation at
      the apical surface and exhibited mucus production and secretion. Asthmatic and
      nonasthmatic cultures secreted similar quantities of IL-8, IL-6, and
      prostaglandin E2. Cultures developed from asthmatic children contained
      considerably more goblet cells and fewer ciliated cells compared with those from
      nonasthmatic children. A well-differentiated model of pediatric epithelium has
      been developed that will be useful for more in vivo like study of the mechanisms
      at play during asthma.

PMID- 19755932
TI  - Measurement of total and compartmental lung volume changes in newborns by
      optoelectronic plethysmography.
AB  - The study of respiratory mechanics in infants requires a noninvasive accurate
      measurement of the lung volume changes (DeltaVL). Optoelectronic plethysmography
      (OEP) allows the assessment of DeltaVL through the measurement of the chest wall
      surface motion and it has been proved to be accurate in adults. The aim of this
      study was to apply OEP to newborns and to validate it by comparison to
      pneumotachography. Twenty term and preterm newborns (GA = 34 +/- 5 wk) in stable
      condition were studied during 1 to 2 min periods of quiet breathing in supine
      position. Airway opening flow was measured by applying a facemask connected to a
      pneumotachograph (PNT) and integrated to provide the DeltaVL. Chest wall volume
      changes were simultaneously measured by OEP. The tidal volume values measured by
      pneumotachography and by OEP were compared for each breath. A total of 771
      breaths from all patients were considered. Bland-Altmann analysis showed a mean
      difference of -0.08 mL and a limit of agreement ranging from -2.98 to 2.83 mL.
      Linear regression analysis demonstrated good correlation between the two
      techniques (r = 0.95, q = 1.00 mL, m = 0.96). OEP provides accurate measurements
      of DeltaVL in newborns and may be useful to study respiratory mechanics and
      breathing patterns during spontaneous breathing and mechanical ventilation.

PMID- 19755933
TI  - Circulating beta chemokine and MMP 9 as markers of oxidative injury in extremely
      low birth weight infants.
AB  - Matrix metalloproteinases (MMPs) and chemokines seem to be induced by hyperoxia
      in preclinical studies. We hypothesized that O2 exposure immediately after birth
      is associated with altered blood spot MMP 9 and beta chemokine concentrations.
      The following analytes were measured on blood spots on d 1 and 3 of life, using
      luminex technology in 1059 infants (birth weights <1000 g) in the NICHD Neonatal
      Research Network: MMP 9, monocyte chemoattractant protein 1 (MCP 1), macrophage
      inflammatory proteins (1alpha and beta), and regulated upon activation, normal t
      cell expressed and secreted (RANTES). Infants administered O2 continually from 6
      to 24 h of life (n = 729), when compared with those with <6 h exposure (n = 330),
      had significantly lower mean birth weight and higher rate of respiratory distress
      syndrome (p < 0.002). On d 3, MCP 1 was higher and RANTES lower among infants
      with early prolonged O2 exposure. After adjusting for covariates, prolonged early
      O2 exposure retained a statistically significant association with higher MCP 1 on
      d 3 (p = 0.003). The consistent association between O2 exposure and MCP 1 among
      extremely preterm infants suggests that further investigation of its role in
      oxidative injury is warranted.

PMID- 19755934
TI  - 2009 ISSLS Prize Winner: What influence does sustained mechanical load have on
      diffusion in the human intervertebral disc?: an in vivo study using serial
      postcontrast magnetic resonance imaging.
AB  - STUDY DESIGN: An in vivo study of the effects of mechanical loading on transport
      of small solutes into normal human lumbar intervertebral discs (IVD) using serial
      postcontrast magnetic resonance imaging (MRI). OBJECTIVE: To investigate the
      influence of a sustained mechanical load on diffusion of small solutes in and out
      of the normal IVD. SUMMARY OF BACKGROUND DATA: Diffusion is an important source
      of disc nutrition and the in vivo effects of load on diffusion in human IVD
      remains unknown. METHODS: Forty normal lumbar discs (on MRI) in 8 healthy
      volunteers were subjected to serial post contrast (Gadoteridol) 3 Tesla MRI in 2
      phases. In phase 1 (control), volunteers were scanned at different time points-
      precontrast and 1.5, 3, 4.5, 6, and 7.5 hours postcontrast injection. In phase 2,
      1 month later, the same volunteers were subjected to sustained supine loading for
      4.5 hours. MRI scans were performed precontrast (preload) and postcontrast
      (postloading) at 1.5, 3, and 4.5 hours. Their spines were then unloaded and
      recovery scans performed at 6 and 7.5 hours postcontrast. In house software was
      used to analyze images. RESULTS: Repeated-measures ANOVA and pairwise comparisons
      at different time points in the central region of the loaded disc (LD) compared
      to the unloaded discs (UD) revealed significantly lower signal intensity ratios
      (P1.5h:P3h:P4.5h<0.001:<0.001:<0.002) indicating reduction in transport rates for
      the LDs. Signal intensity ratios continued to rise in LD for 3 hours into
      recovery phase,whereas UD at the same time point showed a decrease (mean +/- SD =
      0.08 +/- 0.08 vs. -0.21 +/- 0.03). CONCLUSION: Sustained supine creep loading
      (50% body weight) for 4.5 hours retards transport of small solutes into the
      center of human IVD and it required 3 hours of accelerated diffusion in recovery
      state for LD to catch-up with diffusion in UD. The study supports the theory that
      sustained mechanical loading impairs diffusion of nutrients entering the disc and
      quite possibly accelerates disc degeneration.

PMID- 19755936
TI  - 2009 ISSLS Prize Winner: Does discography cause accelerated progression of
      degeneration changes in the lumbar disc: a ten-year matched cohort study.
AB  - STUDY DESIGN: Prospective, match-cohort study of disc degeneration progression
      over 10 years with and without baseline discography. Objectives. To compare
      progression of common degenerative findings between lumbar discs injected 10
      years earlier with those same disc levels in matched subjects not exposed to
      discography. Summary of Background Data. Experimental disc puncture in animal and
      in vivo studies have demonstrated accelerated disc degeneration. Whether
      intradiscal diagnostic or treatment procedures used in clinical practice causes
      any damage to the punctured discs over time is currently unknown. METHODS:
      Seventy-five subjects without serious low back pain illness underwent a protocol
      MRI and an L3/4, L4/5, and L5/S1 discography examination in 1997. A matched group
      was enrolled at the same time and underwent the same protocol MRI examination.
      Subjects were followed for 10 years. At 7 to 10 years after baseline assessment,
      eligible discography and controlled subjects underwent another protocol MRI
      examination. MRI graders, blind to group designation, scored both groups for
      qualitative findings (Pfirrmann grade, herniations, endplate changes, and high
      intensity zone). Loss of disc height and loss of disc signal were measured by
      quantitative methods. RESULTS: Well matched cohorts, including 50 discography
      subjects and 52 control subjects, were contacted and met eligibility criteria for
      follow-up evaluation. In all graded or measured parameters, discs that had been
      exposed to puncture and injection had greater progression of degenerative
      findings compared to control (noninjected) discs: progression of disc
      degeneration, 54 discs (35%) in the discography group compared to 21 (14%) in the
      control group (P = 0.03); 55 new disc herniations in the discography group
      compared to 22 in the control group (P = 0.0003). New disc herniations were
      disproportionately found on the side of the anular puncture (P = 0.0006). The
      quantitative measures of disc height and disc signal also showed significantly
      greater loss of disc height (P = 0.05) and signal intensity (P = 0.001) in the
      discography disc compared to the control disc. CONCLUSION: Modern discography
      techniques using small gauge needle and limited pressurization resulted in
      accelerated disc degeneration, disc herniation, loss of disc height and signal
      and the development of reactive endplate changes compared to match-controls.
      Careful consideration of risk and benefit should be used in recommending
      procedures involving disc injection.

PMID- 19755935
TI  - Degenerative spondylolisthesis: does fusion method influence outcome? Four-year
      results of the spine patient outcomes research trial.
AB  - STUDY DESIGN: Clinical trial subgroup analysis. OBJECTIVE: To compare outcomes of
      different fusion techniques treating degenerative spondylolisthesis (DS). Summary
      of Background Data. Surgery has been shown to be more effective than nonoperative
      treatment out to 4 years. Questions remain regarding the differential effect of
      fusion technique. METHODS: Surgical candidates from 13 centers in 11 states with
      at least 12 weeks of symptoms and confirmatory imaging showing stenosis and DS
      were studied. In addition to standard decompressive laminectomy, 1 of 3 fusion
      techniques was employed at the surgeon's discretion: posterolateral in situ
      fusion (PLF); posterolateral instrumented fusion with pedicle screws (PPS); or
      PPS plus interbody fusion (360 degrees). Main outcome measures were the SF-36
      bodily pain (BP) and physical function (PF) scales and the modified Oswestry
      Disability Index (ODI) assessed at 6 weeks, 3 months, 6 months, and yearly to 4
      years. The as-treated analysis combined the randomized and observational cohorts
      using mixed longitudinal models adjusting for potential confounders. RESULTS: Of
      380 surgical patients, 21% (N = 80) received a PLF; 56% (N = 213) received a PPS;
      17% (N = 63) received a 360 degrees; and 6% (N = 23) had decompression only
      without fusion. Early outcomes varied, favoring PLF compared to PPS at 6 weeks
      (PF: 12.73 vs. 6.22, P < 0.020) and 3 months (PF: 25.24 vs.18.95, P < 0.025) and
      PPS compared to 360 degrees at 6 weeks (ODI: -14.46 vs. -9.30, P < 0.03) and 3
      months (ODI: -22.30 vs. -16.78, P < 0.02). At 2 years, 360 degrees had better
      outcomes: BP: 39.08 versus 29.17 PLF, P < 0.011; and versus 29.13 PPS, P < 0.002;
      PF: 31.93 versus 23.27 PLF, P < 0.021; and versus 25.29 PPS, P < 0.036. However,
      these differences were not maintained at 3- and 4-year follow-up, when there were
      no statistically significant differences between the 3 fusion groups. CONCLUSION:
      In patients with DS and associated spinal stenosis, no consistent differences in
      clinical outcomes were seen among fusion groups over 4 years.

PMID- 19755937
TI  - Identification of cell proliferation zones, progenitor cells and a potential stem
      cell niche in the intervertebral disc region: a study in four species.
AB  - STUDY DESIGN: Descriptive experimental study in 4 different mammals. OBJECTIVE:
      To investigate cell proliferation/regeneration and localize stem cells/progenitor
      cells within the intervertebral disc (IVD). SUMMARY OF BACKGROUND DATA: Disc
      degeneration (DD) is believed to play a major role in patients with chronic
      lumbar pain. Lately, biologic treatment options for DD have gained increasing
      interest. Normal regeneration processes within the IVD and have previously been
      sparsely described and therefore it is of great interest to increase the
      knowledge about these processes. Methods. Detection of cell proliferations zones
      and label-retaining cells were done by in vivo 5-bromo-2-deoxyuridine (BrdU)
      labeling in 18 rabbits, killed after 4, 6, 10, 14, 28, or 56 days. Results were
      visualized with immunohistochemistry and fluorescence/confocal microscopy.
      Localization of progenitor cell were further investigated by immunohistochemistry
      using antibodies towards Notch1, Delta4, Jagged1, C-KIT, KI67, and Stro-1 in
      normal IVD from rabbits (n = 3), rats (n = 2), minipigs (n = 2), and in human
      degenerated IVD (n = 4). Further, flowcytometry analysis using progenitor markers
      were performed on additional human IVD cells (n = 3). RESULTS: BrdU positive
      cells were found in comparable numbers at early and late time points in most
      regions of the anulus fibrosus (AF) and nucleus pulposus demonstrating slow
      ongoing cell proliferation. In the AF border to ligament zone (AFo) and the
      perichondrium region (P) a stem cell niche-like pattern was determined (a high
      number of BrdU positive cells at early time points vs. only a few label retaining
      cells at later time points). In normal and DD tissue from the 4 investigated
      species progenitor cell markers were detected. Conclusion. The IVD is a tissue
      with ongoing slow cell proliferation both in the AF and the nucleus pulposus. The
      stem cell niche pattern detected in AFo and P can be suggested to play a role for
      IVD morphology and function. These findings may be of importance for the
      development of biologic treatment strategies.

PMID- 19755938
TI  - Effects of remifentanil on convulsion duration and hemodynamic responses during
      electroconvulsive therapy: a double-blind, randomized clinical trial.
AB  - BACKGROUND: Among the drugs used for the induction of anesthesia for
      electroconvulsive therapy (ECT), thiopental induces a greater degree of
      cardiovascular alteration than other agents. Remifentanil has been found to
      reduce blood pressure and heart rate when administered as an adjuvant during
      general anesthesia, with unknown effects on the duration of motor or
      electroencephalographic seizure activity during ECT. The purpose of this
      prospective, randomized, double-blind, placebo-controlled, crossover study was to
      evaluate the effects of supplementing thiopental anesthesia with remifentanil on
      convulsion duration and cardiovascular response during ECT. METHODS: Twenty-four
      American Society of Anesthesiologists I and II patients receiving 6 sessions of
      ECT were randomly allocated to 2 groups. All patients were premedicated with
      atropine (0.4 mg, intravenously), then anesthesia was induced by thiopental (1.0
      mg/kg), succinylcholine (0.5 mg/kg), and remifentanil (1.0 microg/kg) in the case
      group or normal saline (3 mL) in the control group in a crossover format.
      Stimulus amplitude for applying ECT was kept constant during the sessions of
      treatment in the course of study for each patient. Hemodynamic parameters,
      convulsion duration, and recovery parameters were recorded. Statistical analysis
      was done using paired t tests. RESULTS: There was no statistically significant
      difference between the groups regarding convulsion duration, recovery times to
      eye opening, obeying specific commands, and walking without help. Remifentanil
      significantly attenuated the increase in heart rate and arterial blood pressure
      (P < 0.05). CONCLUSIONS: Remifentanil (1 microg/kg) administered before
      thiopental (1 mg/kg) has no adverse effect on the duration of ECT-induced
      convulsion and recovery time, but it can attenuate the increase in heart rate and
      arterial blood pressure.

PMID- 19755939
TI  - Treatment of bullous pemphigoid and pemphigus. The French experience, 2009
      update.
AB  - There have been several recent advances in the management of auto-immune
      blistering diseases. The aim of this review was to provide an update, based on
      ''expert'' interpretation of published evidences on the treatments of pemphigoid
      and pemphigus. A literature search (Pubmed) of all randomized controlled trials
      that had not been included in two reviews published by the Cochrane Skin Group in
      2005 on pemphigoid and 2009 on pemphigus have been performed. Recent series of
      pemphigus cases treated with anti-CD20 antibodies have also been reviewed.
      Concerning pemphigoid there is good evidence that high dose topical clobetasol
      propionate should be the first line treatment, and that further studies should
      focus on the finding of simple and well tolerated maintenance therapy. For
      pemphigus, after decades of inconclusive trials, there is now some evidence of a
      moderate efficacy of azathioprine, cyclophosphamide, mycophenolate in addition to
      corticosteroids and may be of intravenous immunoglobulins. The practical impact
      of such evidence is strongly challenged by the possible superiority of anti-CD20
      monoclonal antibodies that may emerge as the most efficient treatment of
      pemphigus. Because of concerns on long-term safety, multicenter trials of these
      ''biological'' treatments should be undertaken urgently.

PMID- 19755940
TI  - Cytokines in autoimmune bullous skin diseases. Epiphenomena or contribution to
      pathogenesis?
AB  - An increasing number of publications reports altered expression of numerous
      cytokines in autoimmune bullous skin diseases. However, with few exceptions, the
      pathogenic relevance of increased levels in serum and blister fluid as well as
      elevated cytokine expression in the skin has not been addressed. The introduction
      of TNFalfa inhibition into the treatment of several chronic inflammatory and
      autoimmune diseases has clearly demonstrated the potential of an anti-cytokine
      based therapy. As the treatment of autoimmune bullous skin diseases remains a
      therapeutic challenge, introduction of novel treatment options for these patients
      is needed. Therefore, we here present the current understanding of the role of
      cytokines in autoimmune bullous skin diseases; focusing on pemphigus vulgaris and
      bullous pemphigoid as representative autoimmune bullous skin diseases, and on the
      cytokines TNFalfa, IL-1 and IL-6, as respective inhibitory compounds have been
      licensed. Increased levels of these 3 chemokines have been found in both sera and
      blister fluid of patients with pemphigus vulgaris and bullous pemphigoid, and for
      most, disease activity correlates with cytokine levels. In animal models of
      pemphigus vulgaris, deficiency of IL-1 or TNFalfa partially protects from
      pemphigus IgG-induced blister formation. For bullous pemphigoid, circumstantial
      experimental evidence suggests, that inhibition of TNFalfa, IL-1 and IL-6 might
      be a suitable approach to dampen the inflammatory response. These assumptions are
      supported by reports of a therapeutic benefit of TNFalfa inhibition in treatment
      refractory cases of pemphigus and several pemphigoid diseases. In summary, the
      current understanding of the contribution of chemokines to autoimmune bullous
      skin diseases, does not allow to draw final CONCLUSIONS: A more detailed
      understanding of the chemokine network in these disorders is required and may be
      provided by the corresponding experimental models.

PMID- 19755941
TI  - Treatment options in pemphigus.
AB  - The therapy of pemphigus is one of the miracles of modern medicine, having
      transformed an almost invariably fatal disease into one whose mortality is now
      approximately 5%. Nonetheless, major challenges remain in further decreasing
      mortality and reducing the side effects of the potent medications used to treat
      this disease. The cornerstone of treatment remains the use of systemic steroids.
      The role of adjuvants, such as immunosuppressive and anti-inflammatory drugs, as
      ''steroid-sparing'' agents, remains to be defined, as there are little randomized
      trial data that provides objective evidence of their effectiveness. More
      recently, biologicals, such as IVIg and rituximab, have been introduced; the
      first to speed the control of active disease unresponsive to conventional
      treatment and the second to increase the proportion of patients in whom a
      complete clinical remission can be induced.

PMID- 19755942
TI  - Treatment options for pemphigus foliaceus.
AB  - Pemphigus foliaceus belongs to a group of rare autoimmune blistering
      mucocutaneous conditions. Systemic corticosteroids have markedly reduced the
      mortality from the disease but its utility is restricted by adverse events. This
      is further complicated by the fact that steroid-sparing agents are also
      associated with serious adverse events and there are only few randomized
      controlled trials demonstrating a beneficial response from the use of these
      agents. Azathioprine and mycophenolate mofetil appear to be the most feasible
      first line adjunctive agents in terms of inducing and maintaining remission and
      harboring a comparatively favourable side effect profile. An enhanced
      understanding of the pathogenesis of pemphigus has resulted in the implementation
      of a number of novel therapies including biological agents, intravenous
      immunoglobulin, and extracorporeal treatment modalities. These therapies have
      also been mainly studied through case series reports, are expensive and/or
      difficult to access in some centres, and are associated with a number of
      deleterious side effects. Rituximab, the anti-CD20 chimeric monoclonal antibody,
      is currently emerging as the therapy of choice in severe refractory disease.
      Further studies on the effects and safety profiles of more specific agents, such
      as peptide immunotherapy and the targeting of intracellular signalling molecules
      involved in the pathogenesis of pemphigus are needed.

PMID- 19755943
TI  - Response in patients with pemphigus vulgaris to rituximab therapy. Basis of the
      biology of B cells.
AB  - Rituximab (RTX) is a chimeric monoclonal antibody against CD20, which is present
      on B lymphocytes on the cell surfaces. Originally used for the treatment of B
      cell malignancies, recent studies show that RTX induced depletion of B cells
      resulted in a significant improvement on patients with pemphigus vulgaris (PV).
      This study enrolled 88 patients treated by the lymphoma protocol. A total of
      80.7% had a complete response, 11.8% had a partial response, 5.7% did not respond
      and 2.3% died. The infection rate was 14.7%. Seventeen percent of patients had
      recurrence. Only 20.4% of the patients could discontinue concomitant therapies
      after RTX. The remaining had a reduction in the dosages but continued it. In 11%
      patients during a six-month period a total of 10 infusions of RTX and intravenous
      immunoglobulins (IVIg) were given. All patients had a complete response. Partial
      responders and non-responders were not reported. In two patients (18.2%) a
      recurrence, which responded to RTX and IVIg, was reported. No mortality or
      infections were observed. At a follow-up of 32 months post-RTX patients were
      still in a remission. Though the number of patients treated is limited, clinical
      outcomes appear to be better and lasting in the protocol using RTX and IVIg
      compare to RTX alone. One of the explanations for these differences in clinical
      outcomes may lie in the fact that the biological behavior of B cells in lymphoma
      patients is different from that in patients with autoimmune diseases.

PMID- 19755944
TI  - Autoimmunity in bullous pemphigoid.
AB  - Bullous pemphigoid (BP) is an autoimmune blistering disease primarily of the
      elderly, characterized by the development of urticarial plaques surmounted by
      subepidermal blisters and the deposition of immunoglobulins and complement at the
      basement membrane zone (BMZ). Immunologically, it is characterized by the
      development of autoantibodies targeting two structural proteins of the
      hemidesmosomes, BP180 (collagen XVII) and BP230. BP230 is intracellular protein
      of the hemidesmosomal plaque, while BP180 is a transmembrane protein with a
      collagenous extracellular domain. The weight of experimental evidence indicates
      that BP180 is the primary target of the pathogenic autoantibodies. Autoantibodies
      are of both the IgG or IgE class, and their binding in the skin triggers
      complement activation, mast cell degranulation and the accumulation of
      inflammatory cells, including eosinophils, mast cells, and neutrophils. Release
      of proteases from these inflammatory cells results in cleavage of the BMZ and
      blister formation. While the initial triggers of autoantibody production remain
      obscure, a better understanding of the pathomechanisms of blister formation will
      lead to the development of new therapeutic strategies.

PMID- 19755945
TI  - Experimental animal models of bullous pemphigoid.
AB  - Bullous pemphigoid (BP) is a cutaneous autoimmune blistering disease
      characterized immunohistologically by dermal-epidermal junction separation, an
      inflammatory cell infiltrate in the upper dermis, and autoantibodies directed
      against the hemidesmosomal proteins BP230 and BP180. A passive transfer mouse
      model of BP that uses rabbit antibodies targeted against murine BP180 reproduces
      the key clinical and histological features of human BP. Using this model, it has
      been demonstrated that subepidermal blistering is initiated by anti-BP180
      antibodies and mediated by complement activation, mast cell degranulation,
      neutrophil infiltration, and proteinase secretion. The rabbit-anti mouse IgG
      passive transfer model is not compatible with study of human pathogenic
      antibodies, as the human and murine antigenic epitopes are not cross-reactive.
      Two humanized mouse models in which the murine form of BP180 is replaced the
      human homologue have recently emerged. Autoantibodies isolated from human
      patients induce experimental BP in the humanized mice, and disease progression
      mirrors that observed in the rabbit-anti mouse IgG model. The humanized mouse
      models present ideal in vivo systems to test novel therapeutic strategies for
      disease management. In this review, we discuss the progress made in understanding
      the pathogenesis of BP, as well as the limits of using animal models to
      investigate human disease.

PMID- 19755946
TI  - Optimizing ALA-PDT in the management of non-melanoma skin cancer by fractionated
      illumination.
AB  - The aim of this review was to describe briefly the mechanism and history of
      photodynamic therapy (PDT). The achieved preclinical and clinical results in
      Rotterdam are discussed in the light of a search to optimize aminolevulinic acid
      photodynamic therapy (ALA-PDT). As the incidence of skin cancer is rising, an
      optimized treatment in non-melanoma skin cancer is needed.

PMID- 19755947
TI  - Actinic keratosis: precancer, squamous cell carcinoma, or marker of field
      cancerization?
AB  - The early detection, recognition, and progression of the actinic keratosis (AK)
      and its relationship with squamous cell carcinoma have long been an area of
      debate. Recent advancements in medicine have examined the role of field
      cancerization in a variety of tumors. The role of AK as a marker for field
      cancerization will be here discussed.

PMID- 19755948
TI  - The current options in the management of actinic keratosis.
AB  - Actinic keratosis is a precursor for squamous cell skin cancer. Hence, it is
      important to treat. For single actinic keratoses, cryo surgery is recommended.
      For widespread actinic keratoses, imiquimod, photodynamic therapy (PDT) or 5-FU
      may be used. ''One-shot'' treatments are advocated as prolonged treatment over
      several weeks probably diminishes patient compliance. Consequently, cryo surgery
      for single actinic keratoses and PDT for widespread actinic keratoses should
      primarily be recommended.

PMID- 19755949
TI  - Treatment options for non-melanoma skin cancer.
AB  - Non melanoma skin cancers (basal cell carcinoma and squamous cell carcinoma) are
      becoming more common. There are many treatments including surgical modalities,
      use of electromagnetic radiations (as in photodynamic therapy), topical and
      intralesional chemotherapies and immunomodulating treatments. The choice as to
      how to treat a particular tumour depends not only on features of the tumour but
      characteristics of the patient and his or her preferences. There are up to date
      guidelines available that are useful when chosing treatments, but following these
      guidelines is not always appropriate to the individual. This is a personal review
      in which the author explains some of the reasons why he recommends one treatment
      over another in particular situations.

PMID- 19755950
TI  - Topical management of actinic keratosis and field cancerisation.
AB  - Actinic keratosis (AK) is a squamous cell carcinoma of the epidermis in situ. In
      around 10% of all patients with AK and in approximately 30% of patients with
      additional immune suppression an invasive squamous cell carcinoma of the skin is
      subsequently observed highlighting that AKs should be identified and treated
      early. The hallmarks and characteristic features of non-melanoma skin cancer have
      been defined histologically: histopathology allows the differentiation based on a
      small tissue sample and remains the gold standard for diagnosis. For all
      therapies the objective is to cure lesions, both clinically and histologically,
      by the destruction of mutated keratinocytes and to reduce the numbers of AK
      lesions with the minimum of pain, scarring and recurrence. The presence of AKs
      are related to exposure to ultra violet radiation, thus all treatments should be
      combined with a reduction in exposure to sunlight. There are a number of
      treatment options currently available, including excision, curettage and
      desiccation, cryotherapy, laser therapy or topical treatments including,
      imiquimod, photodynamic therapy, cox-1/2 inhibitors, chemical peels or 5
      fluorouracil, but not all are appropriate for all patients or all lesions. Often
      treatments are individualized to ensure maximum response. Although existing
      treatments can be highly effective, they have certain limitations such as poor
      patient tolerability or, particularly as AKs occur on exposed areas, they are
      cosmetically unacceptable. In addition, recurrence rates vary for different
      treatments. Recurrence of a lesion (which by definition affects the same site) is
      often the result of incomplete removal of clinically apparent AK lesions after
      treatment or the presence of subclinical lesions that were not identified and
      removed. AK lesions can be treated individually or, if the lesions are numerous
      in an area of sun-damaged skin the whole area should be treated to remove
      subclinical lesions as well as those clinically visible (field-directed
      therapy).Overall the treatment choice is based on several factors, including
      location and number of lesions, growth and morphology, area of sun-damaged skin,
      age, lifestyle, and factors related to previous treatment or patient history.

PMID- 19755951
TI  - The effect of summer holidays and sun exposure on atopic dermatitis.
AB  - AIM: The aim of this study was to investigate the effect of sunlight during
      summer holidays and to assess the seasonability of atopic dermatitis in 43
      consecutive patients with mild-moderate atopic dermatitis referring to the
      Pediatric Outpatient Clinic of the University of Bologna. METHODS: Patients had
      to answer an open questionnaire. RESULTS: The collected data showed that 74.4% of
      the patients affected by mild-moderate atopic dermatitis had complete resolution
      during summer holidays, 16.3% had improvement and only 9.3% had no modification
      of atopic dermatitis severity, confirming the seasonability of the disease, with
      improvement during summertime and worsening in the other seasons. Seaside
      holidays produced a significantly greater improvement than mountains holidays,
      with complete resolution of the disease in 91.2% versus 11.1% of patients,
      P<0.01. Conclusion. These data support the hypothesis on the positive effect of
      UV radiation on atopic dermatitis in patients without eczema after local therapy
      with corticosteroids or immunomodulators, but are in contrast with those reported
      by other authors from Northern Europe. This discrepancy is probably due to the
      latitude and different climate. In the Mediterranean area and in southern
      locations greater improvements are observable.

PMID- 19755952
TI  - Cutaneous T cell lymphoma-mycosis fungoides and Sezary syndrome: an update.
AB  - Mycosis fungoides (MF) is the most common form of cutaneous T cell lymphoma
      (CTCL) and, for unclear reasons, its incidence appears to be increasing. Due to
      significant differences in biological behavior, cutaneous T cell lymphomas have
      recently been reclassified. MF and Sezary syndrome (SS) are now separately
      classified as indolent and aggressive CTCLs, respectively. The cause of MF and SS
      remains elusive. Because establishing the diagnosis of MF, particularly in early
      stages of disease, is often difficult, a guideline with clinical and histological
      diagnostic criteria has recently been proposed. With the exception of very early
      stage disease, no cure is available. However, the number of available therapeutic
      options has increased considerably in recent years, and partial and complete
      remissions are achievable. Prognosis and selection of appropriate therapy largely
      depends on stage of disease. A detailed practice guideline with an algorithmic,
      stage-based approach to therapy has recently been put forth and will likely aid
      clinicians in managing patients with MF and SS. Despite the indolent nature in
      most individuals, the disease has a tremendous psychological impact, not only
      because of the visible nature of the skin lesions, but also due to the rarity of
      the disease and its chronicity. Knowledge of this disease, therapeutic options
      and expectations of therapy will greatly enhance care of afflicted patients.

PMID- 19755953
TI  - Neuro-ocular cutaneous syndrome: a case report.
AB  - Neuro-ocular cutaneous syndrome is a rare and little-known illness. It affects
      the ocular apparatus, the nervous system and the skin. The disease causes
      pathologies such as phacomatosis, which is a generic term used to describe small
      cutaneous neoformations, as well as other ectodermal organ malformations (ocular
      apparatus and central nervous system). The symptoms of this disease are ocular,
      neurological and dermatological and can include: corneal opacity, papillary
      coloboma, optical atrophy, epibulbar dermoids, corectopia, palpebral coloboma,
      frontoparietal alopecia, epilepsy, psychomotor delay, pedunculated skin growths,
      a yellowing of the frontal area, milled papules, milled patches of skin,
      cutaneous spotting, familial angioma and hemiplegia. Due to the complexity of
      this disease, it is imperative that specialists (including ophthalmologists,
      neurologists, dermatologists, plastic surgeons, pediatricians and genetics)
      examine a great number of families affected by this rare pathology in a precise,
      accurate and ongoing manner. The clinical case of a 15 year-old patient (who was
      diagnosed at 10 months old) affected by the neuro-ocular cutaneous syndrome will
      be discussed below.

PMID- 19755954
TI  - An unusual bilateral areolar dermatitis.
AB  - This article describes an uncommon clinical manifestation of contact dermatitis
      due to dyed tissues, showing bilateral plaque lesions on the mammary areolas. The
      clinical history, histological and patch testing examinations confirmed the
      diagnosis. The possible triggering factors related with this kind of contact
      dermatitis and possible differential diagnosis are briefly discussed.

PMID- 19755955
TI  - Rituximab in dermatological diseases.
AB  - Rituximab is a chimeric monoclonal antibody currently used for the treatment of
      non-Hodgkin lymphoma that targets the transmembrane protein CD20 of B cells.
      Recently it has also been used for the treatment of several autoimmune diseases,
      including skin disorders such as Paraneoplastic Pemphigus, Pemphigus Vulgaris,
      Pemphigus Foliaceus, Mucosal pemphigoid, Bullous pemphigoid, Epidermolysis
      bullosa acquisita, Systemic lupus erythematous and Dermatomyositis. Frequently
      all these conditions required intolerably high doses of corticosteroids and
      additional immunosoppressants, which can increase the risk of severe adverse
      events. Therefore, new therapeutic options are needed for such patients. The
      intent of the authors in this review is to provide the reader with a panoramic
      view of the studies reported to date.

PMID- 19755956
TI  - Guttate psoriasis triggered by chickenpox.

PMID- 19755957
TI  - A lifelong onychogryphosis.

PMID- 19755958
TI  - Ocular complication following acute gonorrea.

PMID- 19755959
TI  - Microinjection techniques for studying mitosis in the Drosophila melanogaster
      syncytial embryo.
AB  - This protocol describes the use of the Drosophila melanogaster syncytial embryo
      for studying mitosis. Drosophila has useful genetics with a sequenced genome, and
      it can be easily maintained and manipulated. Many mitotic mutants exist, and
      transgenic flies expressing functional fluorescently (e.g. GFP) - tagged mitotic
      proteins have been and are being generated. Targeted gene expression is possible
      using the GAL4/UAS system. The Drosophila early embryo carries out multiple
      mitoses very rapidly (cell cycle duration, asymptotically equal to 10 min). It is
      well suited for imaging mitosis, because during cycles 10-13, nuclei divide
      rapidly and synchronously without intervening cytokinesis at the surface of the
      embryo in a single monolayer just underneath the cortex. These rapidly dividing
      nuclei probably use the same mitotic machinery as other cells, but they are
      optimized for speed; the checkpoint is generally believed to not be stringent,
      allowing the study of mitotic proteins whose absence would cause cell cycle
      arrest in cells with a strong checkpoint. Embryos expressing GFP labeled proteins
      or microinjected with fluorescently labeled proteins can be easily imaged to
      follow live dynamics (Fig. 1). In addition, embryos can be microinjected with
      function-blocking antibodies or inhibitors of specific proteins to study the
      effect of the loss or perturbation of their function. These reagents can diffuse
      throughout the embryo, reaching many spindles to produce a gradient of
      concentration of inhibitor, which in turn results in a gradient of defects
      comparable to an allelic series of mutants. Ideally, if the target protein is
      fluorescently labeled, the gradient of inhibition can be directly visualized. It
      is assumed that the strongest phenotype is comparable to the null phenotype,
      although it is hard to formally exclude the possibility that the antibodies may
      have dominant effects in rare instances, so rigorous controls and cautious
      interpretation must be applied. Further away from the injection site, protein
      function is only partially lost allowing other functions of the target protein to
      become evident.

PMID- 19755960
TI  - G-rich oligonucleotides inhibit HIF-1alpha and HIF-2alpha and block tumor growth.
AB  - Hypoxia-inducible factor-1 (HIF-1) plays crucial roles in tumor promotion by
      upregulating its target genes, which are involved in energy metabolism,
      angiogenesis, cell survival, invasion, metastasis, and drug resistance. The HIF
      1alpha subunit, which is regulated by O2-dependent hydroxylation, ubiquitination,
      and degradation, has been identified as an important molecular target for cancer
      therapy. We have rationally designed G-rich oligodeoxynucleotides (ODNs) as
      inhibitors of HIF-1alpha for human cancer therapy. The lead compounds, JG243 and
      JG244, which form an intramolecular parallel G-quartet structure, selectively
      target HIF-1alpha and decreased levels of both HIF-1alpha and HIF-2alpha (IC50 <
      2 micromol/l) and also inhibited the expression of HIF-1-regulated proteins
      [vascular endothelial growth factor (VEGF), Bcl-2, and Bcl-XL], but did not
      disrupt the expression of p300, Stat3, or p53. JG-ODNs induced proteasomal
      degradation of HIF-1alpha and HIF-2alpha that was dependent on the hydroxylase
      activity of prolyl-4-hydroxylase-2. JG243 and JG244 dramatically suppressed the
      growth of prostate, breast, and pancreatic tumor xenografts. Western blots from
      tumor tissues showed that JG-ODNs significantly decreased HIF-1alpha and HIF
      2alpha levels and blocked the expression of VEGF. The JG-ODNs are novel
      anticancer agents that suppress tumor growth by inhibiting HIF-1.

PMID- 19755961
TI  - Expanded anticancer therapeutic window of hexon-modified oncolytic adenovirus.
AB  - One of the significant hurdles toward safe and efficacious systemic treatment of
      cancer with oncolytic adenoviruses (Ads) is dose-limiting hepatotoxicity that
      prevents the increase of a therapeutic dose. In this study, we expanded the
      therapeutic window of oncolytic serotype 5 Ad (Ad5) by a genetic modification of
      hypervariable loop 5 (HVR5) in the capsid protein hexon that prevented infection
      of hepatocytes due to ablation of binding to blood factors. This oncolytic virus,
      Ad-GL-HB, had significantly reduced levels of hepatocyte transduction in
      immunocompetent and immunodeficient mice as compared to parental virus Ad-GL. The
      hepatocyte detargeting decreased liver damage and increased the maximum tolerated
      dose of Ad-GL-HB tenfold relative to that of Ad-GL. Intravenous (i.v.) injection
      of Ad-GL or Ad-GL-HB into tumor-bearing mice produced equally increased survival
      rates demonstrating that while Ad-GL-HB detargeted hepatocytes, it sustained
      tumor cell infection after systemic administration. The significantly improved
      safety of the virus allowed it to be used at increased doses for improved
      systemic antitumor efficacy. Our results suggest that hexon modifications provide
      valuable strategies for systemic oncolytic Ad therapy.

PMID- 19755962
TI  - Rescue of pyruvate kinase deficiency in mice by gene therapy using the human
      isoenzyme.
AB  - Human erythrocyte R-type pyruvate kinase deficiency (PKD) is a disorder caused by
      mutations in the PKLR gene that produces chronic nonspherocytic hemolytic anemia.
      Besides periodic blood transfusion and splenectomy, severe cases require bone
      marrow (BM) transplant, which makes this disease a good candidate for gene
      therapy. Here, the normal human R-type pyruvate kinase (hRPK) complementary
      (cDNA) was expressed in hematopoietic stem cells (HSCs) derived from pklr
      deficient mice, using a retroviral vector system. These mice show a similar red
      blood cell phenotype to that observed in human PKD. Transduced HSCs were
      transplanted into myeloablated adult PKD mice or in utero injected into
      nonconditioned PKD fetuses. In the myeloablated recipients, the hematological
      manifestations of PKD were completely resolved and normal percentages of late
      erythroid progenitors, reticulocyte and erythrocyte counts, hemoglobin levels and
      erythrocyte biochemistry were restored. Corrected cells preserved their rescuing
      capacity after secondary and tertiary transplant. When corrected cells were in
      utero transplanted, partial correction of the erythrocyte disease was obtained,
      although a very low number of corrected cells became engrafted, suggesting a
      different efficiency of cell therapy applied in utero. Our data suggest that
      transduction of human RPK cDNA in PKLR mutated HSCs could be an effective
      strategy in severe cases of PKD.

PMID- 19755963
TI  - Suppression of FVIII inhibitor formation in hemophilic mice by delivery of
      transgene modified apoptotic fibroblasts.
AB  - The development of inhibitory antibodies to factor VIII (FVIII) is currently the
      most significant complication of FVIII replacement therapy in the management of
      patients with severe hemophilia A. Immune tolerance protocols for the eradication
      of inhibitors require daily delivery of intravenous FVIII for at least 6 months
      and are unsuccessful in 20-40% of treated patients. We hypothesize that tolerance
      can be induced more efficiently and reliably by delivery of FVIII antigen within
      autologous apoptotic cells (ACs). In this study, we demonstrated suppression of
      the T cell and inhibitor responses to FVIII by infusion of FVIII expression
      vector modified apoptotic syngeneic fibroblasts in both naive and preimmunized
      hemophilia A mice. ACs without FVIII antigen exerted modest generalized immune
      suppression mediated by anti-inflammatory signals. However, FVIII expressing
      apoptotic syngeneic fibroblasts produced much stronger antigen-specific immune
      suppression. Mice treated with these fibroblasts generated CD4+ T cells that
      suppressed the immune response to FVIII after adoptive transfer into naive
      recipients and antigen-specific CD4+CD25+ regulatory T cells (Tregs) that
      inhibited the proliferation of FVIII responsive effector T cells in vitro. These
      preclinical results demonstrate the potential for using FVIII vector modified
      autologous ACs to treat high-titer inhibitors in patients with hemophilia A.

PMID- 19755964
TI  - Immunosuppression impairs response to pneumococcal polysaccharide vaccination in
      patients with inflammatory bowel disease.
AB  - OBJECTIVES: The treatment of inflammatory bowel disease (IBD) often includes
      immunosuppressive medications, which may increase the risk of vaccine-preventable
      illnesses. We aimed to assess the impact of immunosuppression on immune responses
      to pneumococcal vaccination in patients with IBD. METHODS: The study design
      consists of a prospective controlled clinical trial. This study was carried out
      at a tertiary-care IBD clinic. The subjects for the study belonged to one of the
      following three groups: adult patients with IBD on combination TNF-blockers and
      immunomodulators (Group A), those without immunosuppressive therapy (Group B),
      and age-matched healthy controls (Group C). The treatment consisted of
      immunization with 23-valent pneumococcal polysaccharide vaccines (PSVs). The main
      outcome was immune response for five serotypes defined as a twofold or greater
      increase from pre-vaccination titers and > or =1 microg post-vaccination titer.
      RESULTS: Sixty-four subjects participated in the study: 20 in Group A, 25 in
      Group B, and 19 in Group C. Pre-vaccination titers were similar among the three
      groups. Vaccine responses were lower in Group A than in Group B (P< or =0.01 for
      four out of five antigens) and Group C (P<0.01 for all five antigens). Overall
      vaccine response was seen in 45, 80, and 85% of Groups A, B, and C (P=0.01),
      respectively. CONCLUSIONS: Immune response to PSV-23 is impaired in Crohn's
      disease (CD) patients on combination immunosuppressive therapy but is normal
      among non-immunosuppressed patients. Given the unpredictable likelihood for
      immunosuppressive therapy, newly diagnosed patients with IBD should undergo
      vaccination before the initiation of immunosuppressive therapy.

PMID- 19755965
TI  - Visceral obesity and insulin resistance as risk factors for colorectal adenoma: a
      cross-sectional, case-control study.
AB  - OBJECTIVES: Colorectal adenoma is known to be associated with obesity, but the
      association between colorectal adenoma and visceral adipose tissue (VAT) area
      measured by abdominal computed tomography (CT) has not been documented clearly.
      In addition, the relationship between insulin resistance and colorectal adenomas,
      which underlies the mechanism that links obesity and colorectal adenoma, has not
      been studied extensively. The aim of this study was to examine VAT area and
      insulin resistance as risk factors of colorectal adenoma. METHODS: A cross
      sectional, case-control study was conducted in Koreans that presented for health
      check-ups. Subjects underwent various laboratory tests, abdominal CT, and
      colonoscopy. VAT, subcutaneous adipose tissue (SAT), and homeostatic metabolic
      assessment (HOMA) index were evaluated as potential risk factors of colorectal
      adenoma in 2,244 age- and sex-matched subjects. RESULTS: According to univariate
      analysis, the prevalences of smoking, hypertension, metabolic syndrome, and
      family history of colorectal cancer were higher in the adenoma group than in the
      normal control group. In addition, body mass index, waist circumference,
      triglyceride, high-density lipoprotein cholesterol, and VAT and SAT areas were
      significantly different in the two groups. According to the multivariate analysis
      adjusted for multiple confounders, VAT area was independently associated with the
      risk of colorectal adenoma (odds ratio (OR)=3.09, 95% confidence interval (CI):
      2.19-4.36, highest quintile vs. lowest quintile). Mean HOMA index was higher in
      the adenoma group than in the control group (OR=1.99, 95% CI: 1.35-2.92, highest
      vs. lowest quintile). CONCLUSIONS: Visceral obesity was found to be an
      independent risk factor of colorectal adenoma, and insulin resistance was
      associated with the presence of colorectal adenoma.

PMID- 19755966
TI  - Empiric quadruple vs. triple therapy for primary treatment of Helicobacter pylori
      infection: Systematic review and meta-analysis of efficacy and tolerability.
AB  - OBJECTIVES: Recent treatment guidelines recommend two first-line therapies for
      Helicobacter pylori infection: proton pump inhibitor (PPI), bismuth,
      tetracycline, and metronidazole (quadruple therapy) or PPI, clarithromycin, and
      amoxicillin (triple therapy). We performed a systematic review and meta-analysis
      to compare the efficacy and tolerability of these regimens as first-line
      treatment of H. pylori. METHODS: A search of MEDLINE, EMBASE, Google Scholar, the
      Cochrane Central Register of Controlled Trials, ACP Journal Club, the Database of
      Abstracts of Reviews of Effectiveness, Cochrane Methodology Register, Health
      Technology Assessment Database, and abstracts from prominent gastrointestinal
      scientific meetings was carried out. Randomized controlled trials (RCTs)
      comparing bismuth quadruple therapy to clarithromycin triple therapy were
      selected for meta-analysis. Two independent reviewers extracted data, using
      standardized data forms. Meta-analysis was carried out with the metan command in
      Stata 10.1. Funnel plots and subgroup analyses were carried out. RESULTS: Nine
      RCTs (N=1,679) were included. Although dosing regimens of clarithromycin triple
      therapy were quite consistent between trials, dosing regimens varied considerably
      for bismuth quadruple therapy. Bismuth quadruple therapy achieved eradication in
      78.3% of patients, whereas clarithromycin triple therapy achieved an eradication
      rate of 77.0% (risk ratio (RR)=1.002, 95% confidence interval (CI): 0.936-1.073).
      There was moderate heterogeneity and no evidence for significant publication
      bias. Subgroup analyses by study location, treatment duration, and study
      population did not account for the heterogeneity. There were no statistically
      significant differences in side effects yielded by quadruple vs. clarithromycin
      triple therapy (RR=1.04, 95% CI: 1.04-1.14). CONCLUSIONS: Quadruple and triple
      therapies yielded similar eradication rates as primary therapy for H. pylori
      infection. Both therapies yielded suboptimal eradication rates. Patient
      compliance and side effects are similar for quadruple and triple therapies.

PMID- 19755967
TI  - Quality of life in GERD and Barrett's esophagus is related to gender and
      manifestation of disease.
AB  - OBJECTIVES: Gastroesophageal reflux disease (GERD) is a common condition that
      affects patients' health-related quality of life (HRQoL). The HRQoL of Barrett's
      esophagus (BE) has been less well studied. Furthermore, it is unknown to what
      extent BE patients suffer from psychological distress as a result of carrying a
      diagnosis of a premalignant condition. We sought to compare BE and GERD
      (stratified by erosive reflux disease (ERD) and non-erosive reflux disease
      (NERD)) with regard to HRQoL and psychological impact. METHODS: In this single
      center study of subjects presenting for elective upper endoscopy, consecutive
      patients with BE and GERD were enrolled. Participants completed questionnaires
      assessing generic HRQoL (medical outcomes study short form-36 (SF-36)), disease
      specific HRQoL (gastrointestinal quality of life index (GIQLI)), a measure of
      psychological distress (the Revised Hopkins Symptom Checklist: SCL-90R), and a
      patient-centered assessment of the impact of disease severity (the GERD health
      related quality of life measure (GERD HRQL)). RESULTS: Patients with BE had the
      lowest symptom severity compared with those suffering from NERD or ERD (GERD
      HRQL: 13.7 vs. 18 and 15.9, respectively, P<0.01). Those with BE also had better
      disease-specific quality of life compared with NERD or ERD patients (GIQLI: 137.2
      vs. 124.3 and 131.0, respectively, P<0.001). After adjusting for potential
      confounding variables including symptom severity and gender, BE patients
      continued to demonstrate better disease-specific HRQoL, scoring 12.2 points
      higher on the GIQLI than NERD patients (95% confidence interval (CI) 5.1-19.3)
      and 16.3 points higher than ERD patients (95% CI 5.4-27.3), as well as better
      generic HRQoL, scoring 4.8 points higher on the SF-36 physical component summary
      than NERD patients (95% CI 0.8-8.8) and 7.1 points higher than ERD patients (95%
      CI 1.2-13.1). There were no significant differences between groups in
      psychological distress, as demonstrated by the SCL-90R global severity index,
      although BE patients scored lower on the somatization domain compared with NERD
      and ERD patients. When stratified by gender, females with NERD and BE had worse
      disease-specific HRQoL than males. CONCLUSIONS: Patients with BE have better
      generic and disease-specific HRQoL when compared with patients suffering from
      NERD and ERD. This difference is only partially attributable to lower symptom
      severity amongs BE patients. Psychological distress did not differ significantly
      amongs groups. Female gender was associated with worsened HRQoL regardless of
      GERD disease manifestation. Though more precise instruments may aid in detecting
      any HRQoL decrements in BE patients because of perceived cancer risk or fear of
      developing or dying from cancer, we were unable to demonstrate an additional
      decrement in HRQoL because of cancer risk in subjects with BE.

PMID- 19755968
TI  - Esophageal dysmotility in children with eosinophilic esophagitis: a study using
      prolonged esophageal manometry.
AB  - OBJECTIVES: The pathophysiology of dysphagia in patients with eosinophilic
      esophagitis (EoE) is unknown but may be related to abnormal esophageal motor
      function. Symptoms rarely occur during stationary esophageal manometry, so it has
      been difficult to establish an association between symptoms and motor events. Our
      aim was to evaluate esophageal motor function in children with EoE with the use
      of stationary manometry and ambulatory prolonged esophageal manometry and pH
      metry (PEMP). METHODS: PEMP was performed in children with EoE and compared with
      controls and children with gastroesophageal reflux disease (GERD). Peristalsis
      was considered effective when the esophageal contractions had a normal amplitude
      and propagation. Results are expressed as mean+/-s.e. RESULTS: Seventeen patients
      with EoE, 13 with GERD, and 11 controls were studied. Values are expressed as
      mean+/-s.e. Stationary manometry identified abnormal peristalsis in 41% of
      children with EoE. During PEMP, children with EoE had an increased number of
      isolated (16.7+/-3.8 vs. 9.5+/-1.6 vs. 6.5+/-1.1; P<0.03) and high-amplitude
      contractions (4.1+/-1.2 vs. 1.8+/-0.8 vs. 0.1+/-0.1; P<0.03), and higher
      percentage ineffective peristalsis both during fasting (70.5%+/-2.5 vs. 57.8%+/
      3.0 vs. 53.8%+/-1.9; P<0.05) and during meals (68.4+/-3.4 vs. 55.3+/-2.8 vs.
      48.1+/-2.8; P<0.05) when compared with children with GERD and controls. Thirteen
      patients with EoE experienced 21 episodes of dysphagia, and all correlated with
      simultaneous abnormal motor function. CONCLUSIONS: PEMP allowed the detection of
      ineffective peristalsis in children with EoE. Symptoms observed in children with
      EoE may be related to esophageal motor dysfunction.

PMID- 19755969
TI  - Fecal calprotectin correlates more closely with the Simple Endoscopic Score for
      Crohn's disease (SES-CD) than CRP, blood leukocytes, and the CDAI.
AB  - OBJECTIVES: Studies evaluating the correlation between the widely used Simple
      Endoscopic Score for Crohn's disease (SES-CD) and noninvasive markers are scarce.
      The aim of this study was to evaluate the correlation between the SES-CD and
      fecal calprotectin, C-reactive protein (CRP), blood leukocytes, and the Crohn's
      disease activity index (CDAI). METHODS: Crohn's disease patients undergoing
      complete ileocolonoscopy were prospectively enrolled and scored independently
      according to the SES-CD and the CDAI. SES-CD was defined as follows: inactive 0
      3; mild 4-10; moderate 11-19; and high > or =20. RESULTS: Values in CD patients
      (n=140 ileocolonoscopies) compared with controls (n=43) are as follows:
      calprotectin, 334+/-322 vs. 18+/-5 microg/g; CRP, 26+/-29 vs. 3+/-2 mg/l; and
      blood leukocytes, 9.1+/-3.4 vs. 5.4+/-1.9 g/l (all P<0.001). The SES-CD
      correlated closest with calprotectin (Spearman's rank correlation coefficient
      r=0.75), followed by CRP (r=0.53), blood leukocytes (r=0.42), and the CDAI
      (r=0.38). Calprotectin was the only marker that could discriminate inactive
      endoscopic disease from mild activity (104+/-138 vs. 231+/-244 microg/g,
      P<0.001), mild from moderate activity (231+/-244 vs. 395+/-256 microg/g,
      P=0.008), and moderate from high activity (395+/-256 vs. 718+/-320 microg/g,
      P<0.001). The overall accuracy for the detection of endoscopically active disease
      was 87% for calprotectin (cutoff 70 microg/g), 66% for elevated CRP, 54% for
      blood leukocytosis, and 40% for the CDAI > or =150. CONCLUSIONS: Fecal
      calprotectin correlated closest with SES-CD, followed by CRP, blood leukocytes,
      and the CDAI. Furthermore, fecal calprotectin was the only marker that reliably
      discriminated inactive from mild, moderate, and highly active disease, which
      underlines its usefulness for activity monitoring.

PMID- 19755970
TI  - Rigorous histopathological assessment of the colectomy specimen in patients with
      inflammatory bowel disease unclassified does not predict outcome after ileal
      pouch-anal anastomosis.
AB  - OBJECTIVES: Abdominal colectomy has been used in patients with inflammatory bowel
      disease unclassified (IBDU), requiring surgery to allow histopathological
      evaluation of the colectomy specimen to rule out Crohn's disease (CD). We
      evaluated whether any histopathological feature was associated with an adverse
      postoperative outcome. METHODS: Patients with ulcerative colitis (UC) or IBDU
      undergoing ileal pouch-anal anastomosis (IPAA) were prospectively examined. A
      checklist of 17 histopathological features atypical for UC was developed.
      Outcomes of acute pouchitis (AP), chronic pouchitis (CP), and de novo CD were
      assessed. RESULTS: The 153 study patients included 119 (78%) UC and 34 (22%) IBDU
      patients. The following atypical features were identified (n; %): broad-based
      ulcer (99; 65%), appendiceal involvement (78; 51%), V-shaped ulcer (48; 31%),
      crypt-associated granuloma (42; 27%), isolated giant cells (39; 25%),
      discontinuous active inflammation (36; 24%), slit-like fissure (32; 21%),
      discontinuous chronic inflammation (16; 10%), ileal villous architectural
      distortion (12; 8%), neural hypertrophy (10; 7%), backwash ileitis (10; 7%),
      transmural inflammation (8; 5%), discontinuous ileitis (8; 5%), muscle
      hypertrophy (5; 3%), ileal ulcer (4; 3%), and ileal pyloric metaplasia (1; 1%). A
      total of 29 patients (19%) developed AP, 17 (11%) developed CP, and 13 patients
      (8%) developed de novo CD. On univariate analysis, de novo CD developed in 3 of
      the 10 patients (30%) with neural hypertrophy compared with only 10 of the 143
      patients (7%) without neural hypertrophy (P=0.01). Multivariate regression did
      not show a single atypical histopathological feature, which predicted a worse
      outcome after IPAA. CONCLUSIONS: No single atypical histopathological feature of
      UC, or combination of features, was associated with any adverse pouch outcome
      after IPAA. There seems to be no value in performing a staged IPAA in IBDU
      patients.

PMID- 19755971
TI  - Prospective evaluation of anti-tumor necrosis factor therapy guided by magnetic
      resonance imaging for Crohn's perineal fistulas.
AB  - OBJECTIVES: Anti-tumor necrosis factor (TNF) therapy heals Crohn's fistulas
      clinically, but the rate, extent, and duration to achieve fistula track healing
      are unknown. METHODS: We sought to monitor deep healing, as indicated by magnetic
      resonance imaging (MRI), and to use this to determine treatment duration.
      Clinical and MRI fistula healing (at 6, 12, and 18 months), Crohn's Disease
      Activity Index (CDAI), Perianal Crohn's Disease Activity Index (PDAI), and the
      Inflammatory Bowel Disease Questionnaire were prospectively assessed. RESULTS:
      Thirty-four consecutive patients with perineal fistulas were treated with
      infliximab (19), adalimumab (7; all infliximab failures) and thalidomide (8).
      Median follow-up was 110 weeks (range, 74-161). Baseline MRI: 38% >or=2 tracks,
      21% anolabial/rectovaginal. At latest follow-up, clinical fistula 'response' and
      'closure' were seen in 50 and 46% of antibody-treated patients, respectively. All
      patients stopped thalidomide early due to side effects. Of 26 antibody-treated
      patients, at 6 (n=25), 12 (n=25), and 18 (n=20) months, respectively, MRI showed
      complete healing (20, 28, and 30%, respectively), improvement (68, 72, and 65%),
      no change (12, 0, and 0%) or worsening (0, 0, and 5%). MRI healing at 6 months
      (n=5) persisted at 12 and 18 months, including in two patients who stopped
      treatment at 6 months. Fistula history length and complexity did not influence
      the outcome. The only surgical intervention was seton insertion in one patient.
      The PDAI and CDAI scores decreased, and quality of life improved significantly at
      last follow-up. CONCLUSIONS: MRI fistula resolution was variable and slower than
      clinical healing. Prolonged treatment is often required for internal track
      resolution. Preliminary data suggest once MRI healing has occurred fistulas
      remain healed, while remaining on, or stopping anti-TNFalpha therapy. The use of
      a second antibody is clinically valuable.

PMID- 19755972
TI  - Secondary pouchitis: those with identifiable etiopathogenetic or triggering
      factors.
AB  - Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the
      surgical treatment of choice for the majority of patients with medically
      refractory ulcerative colitis (UC) or UC with dysplasia, or familial adenomatous
      polyposis. Various forms of pouchitis frequently occur after surgery. In fact,
      pouchitis is the most frequent long-term complication of IPAA in patients with
      UC, with a cumulative prevalence of up to 50%. The etiology and pathogenesis of
      pouchitis are not entirely clear. It is generally believed that the initiation
      and development of the disease process of pouchitis is associated with dysbiosis
      of pouch reservoir, as evidenced by a favorable response to antibiotic therapy.
      However, the majority of the patients do not show identifiable etiopathogenetic
      or triggering factors, therefore being labeled to have idiopathic pouchitis. In
      contrast, a subgroup of patients, particularly those with antibiotic-refractory
      pouchitis, may have obvious triggering factors for disease flare-up and
      progression and may be considered to have secondary pouchitis. Therefore,
      pouchitis can be classified on the basis of etiology into idiopathic and
      secondary causes. Approximately 20-30% of patients who present with chronic
      pouchitis have secondary identifiable and triggering factors, including
      cytomegalovirus or Clostridium difficile infection, ischemia, concurrent immune
      mediated disorders, radiation, collagen deposition, and use of nonsteroidal anti
      inflammatory drugs. Careful evaluation of these secondary causes of pouchitis
      that may contribute to resistance to antibiotics should be performed before the
      introduction of next-line medical therapy.

PMID- 19755973
TI  - Stress coping, distress, and health perceptions in inflammatory bowel disease and
      community controls.
AB  - OBJECTIVES: This study compares a community inflammatory bowel disease (IBD)
      sample of individuals with a matched non-IBD community sample of individuals on
      psychological functioning and health perceptions. METHODS: Participants in the
      population-based Manitoba IBD Cohort Study (n=388) were directly compared with
      sex-, age-, and region-matched controls from a national random-sample health
      survey on the aspects of psychological health, coping, and perceived general
      health. RESULTS: Overall, the IBD sample had lower psychological well-being and
      mastery, as well as higher distress than did the non-IBD controls (P<or=0.02).
      Those with IBD used avoidant coping significantly more often, and active coping
      modestly more often than did the non-IBD sample; both had similar levels of "self
      soothing" behaviors. Patients with Crohn's disease and ulcerative colitis had
      similarly poor levels of functioning along these dimensions compared with the non
      IBD sample, as did those with active disease (P<0.01). However, those with
      inactive disease were similar to the non-IBD sample, and had modestly higher
      mastery levels. Whereas nearly half of the non-IBD group reported chronic health
      conditions, those with IBD were threefold more likely to report poorer health
      (odds ratio 3.07, 95% confidence interval: 2.10-4.47). Psychological factors
      explained a greater amount of variance in perceived health for the IBD than for
      the non-IBD sample. CONCLUSIONS: Those with IBD have significantly poorer
      psychological health than do those without IBD and view their general health
      status more negatively, although adaptive stress-coping strategies were similar.
      However, when disease is quiescent there is little detriment to functioning.
      Active disease should be a flag to consider psychological needs in the care of an
      IBD patient.

PMID- 19755974
TI  - Proximal small intestinal microbiota and identification of rod-shaped bacteria
      associated with childhood celiac disease.
AB  - OBJECTIVES: Alterations in the composition of the microbiota in the intestine may
      promote development of celiac disease (CD). Using scanning electron microscopy
      (SEM) we previously demonstrated that rod-shaped bacteria were present on the
      epithelium of proximal small intestine in children with CD but not in controls.
      In this study we characterize the microbiota of proximal small intestine in
      children with CD and controls and identify CD-associated rod-shaped bacteria.
      METHODS: Proximal small intestine biopsies from 45 children with CD and 18
      clinical controls were studied. Bacteria were identified by 16S rDNA sequencing
      in DNA extracted from biopsies washed with buffer containing dithiothreitol to
      enrich bacteria adhering to the epithelial lining, by culture-based methods and
      by SEM and transmission electron microscopy. RESULTS: The normal, mucosa
      associated microbiota of proximal small intestine was limited. It was dominated
      by the genera Streptococcus and Neisseria, and also contained Veillonella,
      Gemella, Actinomyces, Rothia, and Haemophilus. The proximal small intestine
      microbiota in biopsies from CD patients collected during 2004-2007 differed only
      marginally from that of controls, and only one biopsy (4%) had rod-shaped
      bacteria by SEM (SEM+). In nine frozen SEM+ CD biopsies from the previous study,
      microbiotas were significantly enriched in Clostridium, Prevotella, and
      Actinomyces compared with SEM- biopsies. Bacteria of all three genera were
      isolated from children born during the Swedish CD epidemic. New Clostridium and
      Prevotella species and Actinomyces graevenitzii were tentatively identified.
      CONCLUSIONS: Rod-shaped bacteria, probably of the indicated species, constituted
      a significant fraction of the proximal small intestine microbiota in children
      born during the Swedish CD epidemic and may have been an important risk factor
      for CD contributing to the fourfold increase in disease incidence in children
      below 2 years of age during that time.

PMID- 19755975
TI  - Impact of measurement of esophageal acid exposure close to the gastroesophageal
      junction on diagnostic accuracy and event-symptom correlation: a prospective
      study using wireless dual pH monitoring.
AB  - OBJECTIVES: Ambulatory esophageal pH monitoring has limited diagnostic accuracy
      in patients with gastroesophageal reflux disease (GERD), especially in those with
      non-erosive reflux disease (NERD). In addition, there is lack of symptom-reflux
      association in the majority of GERD patients. The aim of this study was to
      evaluate the impact of measuring acid exposure 1 cm above the gastroesophageal
      junction (GEJ) on diagnostic accuracy and symptom correlation in GERD patients
      compared with conventional pH measurements (6 cm above the GEJ) using the
      wireless pH system. METHODS: GERD patients and controls as defined by two
      validated questionnaires (Gastroesophageal Reflux Questionnaire and Reflux
      Disease Questionnaire) were prospectively enrolled. Under direct endoscopic
      vision, two wireless pH capsules (BRAVO, Given Imaging, Yokneam, Israel) were
      placed 6 and 1 cm, respectively, above the GEJ. Receiver operator characteristic
      curves were constructed, and symptom indexes were calculated separately for pH
      measurements at 6-cm (proximal) and 1-cm (distal) locations. RESULTS: A total of
      40 GERD patients (20 erosive esophagitis (EE) and 20 NERD) and 16 controls were
      analyzed. Sensitivity and specificity of abnormal acid exposure times in GERD
      were as follows: proximal: 67 and 66%, distal: 60 and 88%; in EE proximal: 75 and
      81%, distal: 84 and 92%; and in NERD proximal: 61 and 67%, distal: 58 and 66%,
      respectively. The proportion of patients with a positive symptom-reflux
      correlation in GERD was as follows: symptom index (SI): proximal: 35%, distal:
      50%; symptom sensitivity index (SSI): proximal: 25%, distal: 5%; and symptom
      associated probability (SAP): proximal: 30% and distal: 35%. The higher
      proportion of patients with a positive SI distally was due to the EE group (EE,
      proximal: 35% and distal: 65%; NERD, proximal: 35% and distal: 35%). CONCLUSIONS:
      Compared with the traditional location, measurement of acid reflux 1 cm above the
      GEJ improved the diagnostic accuracy as well as symptom correlation in EE, but
      not in NERD patients. Thus, pH monitoring 1 cm above the GEJ for improving the
      diagnosis of NERD cannot be recommended in clinical practice at this time.

PMID- 19755976
TI  - Causes of mortality in patients with peptic ulcer bleeding: a prospective cohort
      study of 10,428 cases.
AB  - OBJECTIVES: Despite advances in endoscopic and pharmacological treatment for
      peptic ulcer bleeding (PUB), mortality remains at 5-10% worldwide. Our aim was to
      investigate the causes of death in a prospective cohort of PUB in a tertiary
      referral center. METHODS: Between 1993 and 2005, all patients with upper
      gastrointestinal bleeding (UGIB) admitted to the Prince of Wales Hospital were
      prospectively registered. Demographic data, characteristics of ulcer, and
      pharmacological, endoscopic, and surgical therapy, were documented. Mortality
      cases were classified as (A) bleeding-related death (A1: uncontrolled bleeding,
      A2: within 48 h after endoscopy, A3: during surgery for uncontrolled bleeding,
      A4: surgical complications or within 1 month after surgery, and A5: endoscopic
      related mortality) or (B) non-bleeding-related death (B1: cardiac causes, B2:
      pulmonary causes, B3: cerebrovascular disease, B4: multiorgan failure, and B5:
      terminal malignancy). RESULTS: In all, 18,508 cases of UGIB were enrolled; among
      them, 10,428 cases from 9,375 patients were confirmed to have PUB, and 577 (6.2%)
      patients died. There were significantly more patients who died of non-ulcer
      bleeding causes (79.7%) than bleeding causes (18.4%). The mean (s.d.) age of
      those who died of bleeding-related causes was higher (75.4 (12.6) years) than
      that of those who died of non-bleeding causes (71.7 (13.1) years) (P=0.010). Most
      bleeding-related deaths occurred when immediate control of bleeding failed
      (29.2%) or when patients died within 48 h after endoscopic therapy (25.5%). Among
      those who died of non-bleeding-related causes, multiorgan failure (23.9%),
      pulmonary conditions (23.5%), and terminal malignancy (33.7%) were most common.
      CONCLUSIONS: The majority of PUB patients died of non-bleeding-related causes.
      Optimization of management should aim at reducing the risk of multiorgan failure
      and cardiopulmonary death instead of focusing merely on successful hemostasis.

PMID- 19755977
TI  - Angiogenic DC-SIGN(+) cells are present at the attachment sites of
      epitheliochorial placentae.
AB  - Spontaneous early and mid-gestation fetal losses occur in swine. At both stages,
      endometrial lymphocytes associated with smaller, paler conceptuses have fewer pro
      angiogenic and more pro-inflammatory cytokine transcripts compared with robust
      conceptuses. We hypothesized that similar differences occur in conceptus
      associated dendritic cells (DCs). Using laser capture-microdissection, dendritic
      cell-specific intercellular adhesion molecule-grabbing non-integrin (DC-SIGN)(+)
      cells were isolated from attachment sites of healthy and arresting conceptuses at
      gestation day (gd)20 and 50. DC-SIGN(+) cells were screened using real-time PCR
      for vascular endothelial cell growth factor (Vegf), its receptors, semaphorins
      (Sema) and plexins (Plxn), and for toll-like receptor (Tlr) transcripts to
      address potential activation pathways. Homogenized endometrial and trophoblast
      biopsies were quantified for type 1/type 2 cytokine transcripts/proteins. DC
      SIGN(+) cells from healthy and arresting conceptuses had more Vegf transcripts at
      early than mid gestation whereas transcripts for Vegfr1 and Vegfr2 were stable.
      In gd20 arresting site DC-SIGN(+) cells, Neuropilin-2 transcripts were elevated,
      whereas at gd50 arresting sites, Plxn-A2 increased and Sema3A transcripts were
      lost. Tlr-1, Tlr-4 and Tlr-6 transcript abundance was independent of conceptus
      health. At gd20, type 1 cytokines were prevalent, whereas at gd50 type 2
      cytokines predominated in endometrium and trophoblast. Thus, gestational
      features, characteristic of haemochorial placentation, are present in species
      with distinctly different placentation.

PMID- 19755980
TI  - Plasmacytoid and conventional dendritic cells are early producers of IL-12 in
      Neospora caninum-infected mice.
AB  - Neospora caninum is a coccidian parasite causative of clinical infections in a
      wide range of animal hosts. The maturation and activation of splenic conventional
      dendritic cells (cDCs) and plasmacytoid dendritic cells (pDCs) were studied here
      in BALB/c mice challenged intraperitoneal with N. caninum tachyzoites. The number
      of cDCs was found to decrease in the spleen of the infected mice 12 h and 2 days
      after the parasitic challenge, whereas at day 5 after infection it was
      significantly above that of mock-infected controls. In contrast, the number of
      splenic pDCs did not change significantly on infection. In the infected mice,
      both cell subtypes displayed an activated phenotype with upregulation of
      costimulatory and MHC class II molecules. This stimulatory effect was more marked
      at the earliest assessed time point after infection, 12 h, when a clear increase
      in the frequency of cDCs (CD8alpha(+) and CD8alpha(-)) and pDCs producing
      interleukin-12 (IL-12) was also observed. N. caninum tachyzoites could be
      observed by confocal microscopy associated with sorted DCs. Overall, these
      results present the first evidence that both cDCs and pDCs mediate in vivo the
      innate immune response to N. caninum infection through the production of IL-12, a
      key cytokine for host resistance to neosporosis.

PMID- 19755981
TI  - Open-label, clinical phase I studies of tasquinimod in patients with castration
      resistant prostate cancer.
AB  - BACKGROUND: Tasquinimod is a quinoline-3-carboxamide derivative with anti
      angiogenic activity. Two open-label phase I clinical trials in patients were
      conducted to evaluate the safety and tolerability of tasquinimod, with additional
      pharmacokinetic and efficacy assessments. METHODS: Patients with castration
      resistant prostate cancer with no previous chemotherapy were enrolled in this
      study. The patients received tasquinimod up to 1 year either at fixed doses of
      0.5 or 1.0 mg per day or at an initial dose of 0.25 mg per day that escalated to
      1.0 mg per day. RESULTS: A total of 32 patients were enrolled; 21 patients were
      maintained for >or=4 months. The maximum tolerated dose was determined to be 0.5
      mg per day; but when using stepwise intra-patient dose escalation, a dose of 1.0
      mg per day was well tolerated. The dose-limiting toxicity was sinus tachycardia
      and asymptomatic elevation in amylase. Common treatment-emergent adverse events
      included transient laboratory abnormalities, anaemia, nausea, fatigue, myalgia
      and pain. A serum prostate-specific antigen (PSA) decline of >or=50% was noted in
      two patients. The median time to PSA progression (>25%) was 19 weeks. Only 3 out
      of 15 patients (median time on study: 34 weeks) developed new bone lesions.
      CONCLUSION: Long-term continuous oral administration of tasquinimod seems to be
      safe, and the overall efficacy results indicate that tasquinimod might delay
      disease progression.

PMID- 19755982
TI  - DKC1 overexpression associated with prostate cancer progression.
AB  - BACKGROUND: Dyskerin encoded by the DKC1 gene is a predominantly nucleolar
      protein essential for the formation of pseudouridine in RNA and the telomerase
      RNA subunit hTR. Inherited mutations inactivating dyskerin cause dyskeratosis
      congenita, a syndrome with progeroid features characterised by skin defects and
      haematopoiesis failure, as well as cancer susceptibility. In this study, we
      report DKC1 overexpression in prostate cancers. METHODS: Expression of DKC1 was
      measured by quantitative RT-PCR in prostate cancer tissues in relation to hTR and
      the proliferation marker MKI67. Effects of dyskerin downregulation on
      proliferation, apoptosis and senescence of prostate cancer cell lines were
      determined. RESULTS: DKC1 was significantly overexpressed in prostate cancers,
      particularly in high-stage and recurring cases, correlating moderately with hTR
      and MKI67. Dyskerin downregulation in prostate carcinoma cell lines by siRNA
      diminished cell proliferation, but elicited neither apoptosis nor senescence.
      Apoptosis induction by TNF-alpha or tunicamycin was not enhanced. Long-term
      downregulation led predominantly to cell shrinking and loss of adhesion.
      INTERPRETATION: DKC1 upregulation in prostate cancers is common and likely to be
      necessary for extensive tumour growth. The phenotype of prostate carcinoma cell
      lines after dyskerin downregulation suggests that its most critical function is
      sustaining protein biosynthesis. Intriguingly, compromised function and
      overexpression of dyskerin can both contribute to cancer development.

PMID- 19755983
TI  - Cytokeratins 18 and 8 are poor prognostic markers in patients with squamous cell
      carcinoma of the oesophagus.
AB  - BACKGROUND: Cytokeratins (CKs) are structural marker proteins specific for
      epithelial cells. However, recent studies indicate their involvement in cancer
      progression. METHODS: We evaluated CK18 and its filament partner, CK8 expression,
      by immunohistochemistry in 210 resected specimens from patients with oesophageal
      squamous cell carcinoma (OSCC). We also analysed the relationship between their
      expression and various clinicopathological parameters including prognosis.
      RESULTS: Neither CK18 nor CK8 was expressed in non-cancerous squamous epithelium
      whereas proper oesophageal glands expressed both CKs. Ninety (42.9%) tumours were
      CK18 positive and 85 (40.5%) CK8 positive, and the concordance rate for
      immunohistochemical classification for CK18 and CK8 was 82.4%. CK18 expression
      correlated with poorly differentiated tumours, use of neo-adjuvant chemotherapy,
      and advanced stage. Prognosis of patients with CK18-positive tumours was poorer
      than that of patients with negative OSCC (P<0.001). A similar trend was noted for
      CK8 expression. Multivariate analysis identified pT (P=0.020), pN number
      (P=0.001), and CK18 expression (P=0.004) as independent prognostic factors. CK18
      expression in 83 pretreatment biopsy specimens was detected in 47 cases (56.6%)
      and also correlated with prognosis (P=0.045). CONCLUSION: CK18/CK8 expression
      correlated with progression of OSCC. The significant correlation with prognosis
      and stable expression in biopsy specimen suggest usefulness of CK18 in selection
      of treatment strategies for OSCC.

PMID- 19755984
TI  - Nuclear receptor co-activators and HER-2/neu are upregulated in breast cancer
      patients during neo-adjuvant treatment with aromatase inhibitors.
AB  - BACKGROUND: Acquired resistance to endocrine therapy in breast cancer is poorly
      understood. Characterisation of the molecular response to aromatase inhibitors in
      breast cancer tissue may provide important information regarding development of
      oestrogen hypersensitivity. METHODS: We examined the expression levels of nuclear
      receptor co-regulators, the orphan nuclear receptor liver receptor homologue-1
      and HER-2/neu growth factor receptor using real-time RT-PCR before and after 13
      16 weeks of primary medical treatment with the aromatase inhibitors anastrozole
      or letrozole. RESULTS: mRNA expression of the steroid receptor co-activator 1
      (SRC-1) and peroxisome-proliferator-activated receptor gamma co-activator-1alpha
      (PGC-1alpha) was correlated (P=0.002), and both co-activators increased during
      treatment in the patient group as a whole (P=0.008 and P=0.032, respectively), as
      well as in the subgroup of patients achieving an objective treatment response
      (P=0.002 and P=0.006). Although we recorded no significant change in SRC
      3/amplified in breast cancer 1 level, the expression correlated positively to the
      change of SRC-1 (P=0.002). Notably, we recorded an increase in HER-2/neu levels
      during therapy in the total patient group (18 out of 26; P=0.016), but in
      particular among responders (15 out of 21; P=0.008). CONCLUSION: Our results show
      an upregulation of co-activator mRNA and HER-2/neu during treatment with
      aromatase inhibitors. These mechanisms may represent an early adaption of the
      breast cancer cells to oestrogen deprivation in vivo.

PMID- 19755985
TI  - Predictive factors for severe toxicity of sunitinib in unselected patients with
      advanced renal cell cancer.

PMID- 19755986
TI  - CD8+ lymphocytes/ tumour-budding index: an independent prognostic factor
      representing a 'pro-/anti-tumour' approach to tumour host interaction in
      colorectal cancer.
AB  - BACKGROUND: The tumour-host interaction at the invasive front of colorectal
      cancer, including the epithelial-mesenchymal transition and its hallmark 'tumour
      budding', is an important area of investigation in terms of prognosis. The aim of
      this study was to determine the prognostic impact of a 'pro-/anti-tumour'
      approach defined by an established 'pro-tumour' (tumour budding) and host-related
      'anti-tumour' factor of the adaptive immunological microenvironment (CD8+
      lymphocytes). METHODS: Double immunostaining for CK22/CD8 on whole tissue
      sections (n=279; Cohort 1) and immunohistochemistry for CD8+ using tissue
      microarrays (n=191; Cohort 2) was carried out. Tumour buds, CD8+ and CD8+ T
      lymphocytes : tumour buds indices were evaluated per high-power field. RESULTS:
      In Cohort 1, a low-CD8+/ buds index was associated with lymph node metastasis
      (P<0.001), vascular invasion (P=0.009), worse survival in univariate (P<0.001)
      and multivariable (P<0.001) analysis, and furthermore in lymph node-negative
      patients (P=0.002). In Cohort 2, the CD8+/ buds index was associated with T stage
      (P<0.001), N stage (P=0.041), vascular invasion (P=0.005) and survival in
      patients with TNM stage II (P=0.019), stage III (P=0.004), and adjuvantly
      untreated (P=0.009) and treated patients (P<0.001). CONCLUSION: The CD8+
      lymphocyte : tumour-budding index is an independent prognostic factor in
      colorectal cancer and a promising approach for a future prognostic score for
      patients with this disease.

PMID- 19755987
TI  - Bladder cancer in cancer patients: population-based estimates from a large
      Swedish study.
AB  - BACKGROUND: This study quantified the risk of urinary bladder neoplasms in cancer
      patients taking into account the age at first diagnosis, the gender of the
      patients and the lead time between diagnoses. METHODS: We used standardised
      incidence ratios (SIRs) to compare the incidence of bladder tumours in 967 767
      cancer patients with the incidence rate in the general Swedish population. A
      total of 3324 male and 1560 female patients developed bladder tumours at least 1
      year after first cancer diagnosis. RESULTS: After bladder and renal pelvis
      cancers, the SIRs of bladder neoplasms were higher in female than in male
      patients. Men affected by lung, stomach and larynx tumours belonged to the
      population at high risk for bladder cancer. Treatment of breast, ovarian and
      cervical cancers seems to contribute to the subsequent development of bladder
      neoplasms. Long latencies (16-25 years) were observed after testicular, cervical
      and endometrial cancers. Detection bias had an important role after prostate
      cancer. Chemotherapy with cyclophosphamide and cisplatin, and also radiotherapy,
      seem to increase the risk of subsequent neoplasms in the bladder. CONCLUSIONS:
      These population-based results may help urologists to assess the risk of bladder
      neoplasms in cancer survivors. Our data should guide ongoing studies that
      investigate the effectiveness of bladder cancer screening in cancer patients.

PMID- 19755988
TI  - Tetraspanin-induced death of myeloma cell lines is autophagic and involves
      increased UPR signalling.
AB  - BACKGROUND: Multiple myeloma (MM) therapy is hindered by the interaction of the
      heterogeneous malignant plasma cells with their microenvironment and evolving
      drug resistance. We have previously shown that the membranal tetraspanins, CD81
      and CD82, are under-expressed in MM cells and that their reintroduction causes
      massive non-apoptotic death. In this study, we aimed to characterise the
      tetraspanin-induced MM death. METHODS: Multiple myeloma cell lines were
      transiently transfected with eGFP-CD81N1/CD82N1 fusion proteins and assessed for
      death mode by flow cytometry (propidium iodide, ZVAD-fmk, 3MA), activation of
      unfolded protein response (UPR), and autophagy (immunoblot, RT-PCR). RESULTS:
      Cell death induced by CD81N1 and CD82N1 in MM cell lines was autophagic and
      involved endoplasmic reticulum (ER)-stress manifested by activation of UPR
      pathways, PERK (protein kinase-like ER kinase) and IRE1 (inositol-requiring 1).
      We also established the relative X-box binding protein 1 baseline expression
      levels in a panel of MM cell lines and their general dependence on autophagy for
      survival. Timeline of UPR cascades and cell fate supported our results.
      INTERPRETATION: This is the first publication implicating tetraspanins in UPR
      signalling pathways, autophagy, and autophagic death. Integration of our findings
      with published data highlights the unifying dependence of MM cells on ER-Golgi
      homoeostasis, and underscores the potential of tetraspanin complexes and ER
      stress as leverage for MM therapy.

PMID- 19755989
TI  - Absence of VHL gene alteration and high VEGF expression are associated with
      tumour aggressiveness and poor survival of renal-cell carcinoma.
AB  - BACKGROUND: The von Hippel-Lindau gene (VHL) alteration, a common event in
      sporadic clear-cell renal-cell carcinoma (CCRCC), leads to highly vascularised
      tumours. Vascular endothelial growth factor (VEGF) is the major factor involved
      in angiogenesis, but the prognostic significance of both VHL inactivation and
      VEGF expression remain controversial. The aims of this study were to analyse the
      relationship between VHL genetic and epigenetic alterations, VHL expression and
      VEGF tumour or plasma expression, and to analyse their respective prognostic
      value in patients with CCRCC. METHODS: A total of 102 patients with CCRCC were
      prospectively analysed. Alterations in VHL were determined by sequencing,
      Multiplex Ligation-dependent Probe Amplification (MLPA) and methylation-specific
      MLPA. Expression of pVHL and VEGF was determined by immunohistochemistry. Plasma
      VEGF was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: VHL
      mutation, deletion and promoter methylation were identified in 70, 76 and 14
      cases, respectively. Overall, at least one VHL-gene alteration occurred in 91
      cases (89.2%). Both VEGF tumour and plasma expression appeared to be decreased in
      case of VHL alteration. Median progression-free survival and CCRCC-specific
      survival were significantly reduced in patients with wild-type VHL or altered VHL
      and high VEGF expression, which, therefore, represent two markers of tumour
      aggressiveness in CCRCC. CONCLUSION: Stratifying CCRCCs according to VHL and VEGF
      status may help tailor therapeutic strategy.

PMID- 19755991
TI  - Human leukocyte antigen class I expression is an independent prognostic factor in
      advanced ovarian cancer resistant to first-line platinum chemotherapy.
AB  - BACKGROUND: Loss of HLA class I is important in ovarian cancer prognosis but its
      role as a prognostic indicator in relation to therapy remains unproven. We
      studied the prognostic potential of this antigen and its significance in relation
      to platinum therapy. METHODS: A total of 157 primary ovarian cancers were
      assessed for HLA class I immunohistochemically and linked to a comprehensive
      database of clinicopathological variables, treatment details, and platinum
      sensitivity. RESULTS: Tumours expressing high levels of HLA class I had
      significantly improved survival (P=0.044). There was a 19-month difference in the
      median overall survival between tumours with high and low antigen expression. HLA
      class I antigen expression, stage, and platinum sensitivity were independently
      predictive of prognosis on multivariate analysis. HLA class I antigen was shown
      to be expressed at higher levels in patients with good overall survival in
      platinum-resistant patients (P=0.042). HLA class I significantly correlated with
      overall survival on multivariate analyses (P=0.034). CONCLUSION: Low-level HLA
      class I expression is an independent prognostic indicator of poor clinical
      outcome in ovarian cancer. The survival advantage of patients with platinum
      resistant tumours expressing high levels of HLA class I suggests that
      immunotherapy may be of use in these ovarian cancers resistant to standard
      chemotherapy.

PMID- 19755992
TI  - Contribution of HIF-1 and drug penetrance to oxaliplatin resistance in hypoxic
      colorectal cancer cells.
AB  - BACKGROUND: Hypoxia is as an indicator of poor treatment outcome. Consistently,
      hypoxic HCT116 colorectal cancer cells are resistant to oxaliplatin, although the
      mechanistic basis is unclear. This study sought to investigate the relative
      contribution of HIF-1 (hypoxia-inducible factor-1)-mediated gene expression and
      drug penetrance to oxaliplatin resistance using three-dimensional spheroids.
      METHODS: Hypoxia-inducible factor-1alpha function was suppressed by the stable
      expression of a dominant-negative form in HCT116 cells (DN). Cells were drug
      exposed as monolayer or multicellular spheroid cultures. Cells residing at
      differing oxygenation status were isolated from Hoechst 33342-treated spheroids
      using flow cytometry. Sub-populations were subjected to clonogenic survival
      assays and to Inductively-Coupled Plasma Mass Spectroscopy to determine
      oxaliplatin uptake. RESULTS: In spheroids, a sensitivity gradient
      (hypoxic<aerobic) was revealed by survival assays and this correlated with levels
      of platinum-bound DNA. The resistance of hypoxic sub-populations exceeded
      relative changes in adduct levels, implicating factors other than drug penetrance
      in cell response. Dominant-negative monolayer cells showed no resistance to
      oxaliplatin in hypoxia and spheroids; the relative resistance of hypoxic compared
      with aerobic sub-populations was reduced compared with those from controls.
      CONCLUSION: Overall, data show that drug penetration, DNA damage levels and HIF-1
      dependent processes, all contribute to the resistance of hypoxic cells to
      oxaliplatin.

PMID- 19755993
TI  - Gene expression profile and response to trastuzumab-docetaxel-based treatment in
      breast carcinoma.
AB  - BACKGROUND: Resistance to trastuzumab is often observed in women with human
      epidermal growth factor receptor 2 (HER2)-positive breast cancer and has been
      shown to involve multiple potential mechanisms. We examined the ability of
      microarray analyses to determine the potential markers of pathological complete
      response (pCR). METHODS: We conducted an analysis of tumours from 38 patients
      with locally advanced HER2-positive breast cancer who had received trastuzumab
      combined with docetaxel. Quantitative reverse transcriptase (RT)-PCR was used to
      assess the expression of 30 key genes; microarray analyses were carried out on 25
      tumours to identify a prognostic gene expression profile, with 13 blinded samples
      used to validate the identified profile. RESULTS: No gene was found to correlate
      with response by RT-PCR. The microarray analysis identified a gene expression
      profile of 28 genes, with 12 upregulated in the pCR group and 16 upregulated in
      non-pCR. The leave-one-out cross-validation test exhibited 72% accuracy, 86%
      specificity, and 55% sensitivity. The 28-gene expression profile classified the
      13 validation samples with 92% accuracy, 89% specificity, and 100% sensitivity.
      CONCLUSION: Our results suggest that genes not involved in classical cancer
      pathways such as apoptosis or DNA repair could be involved in responses to a
      trastuzumab-docetaxel-based regimen. They also describe for the first time a gene
      expression signature that predicts trastuzumab response.

PMID- 19755994
TI  - Chronic lymphocytic leukaemia patients have a high risk of Merkel-cell
      polyomavirus DNA-positive Merkel-cell carcinoma.
AB  - BACKGROUND: Immunosuppression and Merkel-cell polyomavirus (MCPyV) infection may
      have a role in the pathogenesis of Merkel-cell carcinoma (MCC), a rare
      neuroendocrine carcinoma of the skin. METHODS: We studied incidence of chronic
      lymphocytic leukaemia (CLL) and MCC from the files of the Finnish Cancer Registry
      and the largest hospital of Finland, Helsinki University Central Hospital, from
      1979 to 2006. Presence of MCPyV DNA in MCCs was investigated by quantitative PCR.
      RESULTS: We identified 4164 patients diagnosed with CLL and 172 diagnosed with
      MCC. Six patients diagnosed with both diseases were found; CLL was the first
      diagnosis in four cases and MCC in two. The standardised incidence ratio (SIR)
      for CLL after the diagnosis of MCC was highly elevated, 17.9 (95% confidence
      interval (CI), 2.2-64.6; P<0.001), and the SIR for MCC after the diagnosis of CLL
      was also elevated, 15.7 (3.2-46.0, P<0.01). Merkel-cell polyomavirus DNA was
      present in all five MCCs with tumour tissue available for analysis. CONCLUSIONS:
      We conclude that patients diagnosed with CLL have a substantially increased risk
      for MCC, and vice versa. Merkel-cell polyomavirus DNA is frequently present in
      MCCs that occur in CLL patients. Immunosuppression related with CLL and viral
      infection might explain the association between CLL and MCC.

PMID- 19755995
TI  - Design and modification of EGF4KDEL 7Mut, a novel bispecific ligand-directed
      toxin, with decreased immunogenicity and potent anti-mesothelioma activity.
AB  - BACKGROUND: Potency, immunogenicity, and toxicity are three problems that limit
      the use of targeted toxins in solid tumour therapy. METHODS: To address potency,
      we used genetic engineering to develop a novel bispecific ligand-directed toxin
      (BLT) called EGF4KDEL, a novel recombinant anti-mesothelioma agent created by
      linking human epidermal growth factor (EGF) and interleukin-4 (IL-4) to truncated
      pseudomonas exotoxin (PE38) on the same single-chain molecule. Immunogenicity was
      reduced by mutating seven immunodominant B-cell epitopes on the PE38 molecule to
      create a new agent, EGF4KDEL 7Mut. RESULTS: In vitro, bispecific EGF4KDEL showed
      superior anti-mesothelioma activity compared with its monospecific counterparts.
      Toxicity in mice was diminished by having both ligands on the same molecule,
      allowing administration of a 10-fold greater dose of BLT than a mixture of
      monomeric IL4KDEL and EGFKDEL. EGF4KDEL 7Mut, retained all of its functional
      activity and induced about 87% fewer anti-toxin antibodies than mice given the
      parental, non-mutated form. In vivo, intraperitoneal (IP) injection of the BLT
      showed significant (P<0.01) and impressive effects against two aggressive,
      malignant IP mesothelioma models when treatment was begun 14-16 days post tumour
      innoculation. CONCLUSION: These data show that EGF4KDEL 7Mut is a promising new
      anti-mesothelioma agent that was developed to specifically address the obstacles
      facing clinical utility of targeted toxins.

PMID- 19755996
TI  - Overexpression of FOXG1 contributes to TGF-beta resistance through inhibition of
      p21WAF1/CIP1 expression in ovarian cancer.
AB  - BACKGROUND: Loss of growth inhibitory response to transforming growth factor-beta
      (TGF-beta) is a common feature of epithelial cancers. Recent studies have
      reported that genetic lesions and overexpression of oncoproteins in TGF
      beta/Smads signalling cascade contribute to the TGF-beta resistance. Here, we
      showed that the overexpressed FOXG1 was involved in attenuating the anti
      proliferative control of TGF-beta/Smads signalling in ovarian cancer. METHODS:
      FOXG1 and p21(WAF1/CIP1) expressions were evaluated by real-time quantitative
      reverse-transcription polymerase chain reaction (RT-PCR), western blot and
      immunohistochemical analyses. The effect of FOXG1 on p21(WAF1/CIP1)
      transcriptional activity was examined by luciferase reporter assays. Cell lines
      stably expressing or short hairpin RNA interference-mediated knockdown FOXG1 were
      established for studying the gain-or-loss functional effects of FOXG1. XTT cell
      proliferation assay was used to measure cell growth of ovarian cancer cells.
      RESULTS: Quantitative RT-PCR and western blot analyses showed that FOXG1 was
      upregulated and inversely associated with the expression levels of p21(WAF1/CIP1)
      in ovarian cancer. The overexpression of FOXG1 was significantly correlated with
      high-grade ovarian cancer (P=0.025). Immunohistochemical analysis on ovarian
      cancer tissue array was further evidenced that FOXG1 was highly expressed and
      significantly correlated with high-grade ovarian cancer (P=0.048). Functionally,
      enforced expression of FOXG1 selectively blocked the TGF-beta-induced
      p21(WAF1/CIP1) expressions and increased cell proliferation in ovarian cancer
      cells. Conversely, FOXG1 knockdown resulted in a 20-26% decrease in cell
      proliferation together with 16-33% increase in p21(WAF1/CIP1) expression.
      Notably, FOXG1 was able to inhibit the p21(WAF1/CIP1) promoter activity in a p53
      independent manner by transient reporter assays. CONCLUSION: Our results suggest
      that FOXG1 acts as an oncoprotein inhibiting TGF-beta-mediated anti-proliferative
      responses in ovarian cancer cells through suppressing p21(WAF1/CIP1)
      transcription.

PMID- 19755997
TI  - Cutoff value determines the performance of a semi-quantitative immunochemical
      faecal occult blood test in a colorectal cancer screening programme.
AB  - BACKGROUND: The cutoff of semi-quantitative immunochemical faecal occult blood
      tests (iFOBTs) influences colonoscopy referrals and detection rates. We studied
      the performance of an iFOBT (OC-Sensor) in colorectal cancer (CRC) screening at
      different cutoffs. METHODS: Dutch screening participants, 50-75 years of age,
      with average CRC risk and an iFOBT value >or=50 ng ml(-1) were offered
      colonoscopy. The detection rate was the percentage of participants with CRC or
      advanced adenomas (>or=10 mm, >or=20% villous, high-grade dysplasia). The number
      needed to scope (NNTScope) was the number of colonoscopies to be carried out to
      find one person with CRC or advanced adenomas. RESULTS: iFOBT values >or=50 ng
      ml(-1) were detected in 526 of 6157 participants (8.5%) and 428 (81%) underwent
      colonoscopy. The detection rate for advanced lesions (28 CRC and 161 with
      advanced adenomas) was 3.1% (95% confidence interval: 2.6-3.5%) and the NNTScope
      was 2.3. At 75 ng ml(-1), the detection rate was 2.7%, the NNTScope was 2.0 and
      the CRC miss rate compared with 50 ng ml(-1) was <5% (N=1). At 100 ng ml(-1), the
      detection rate was 2.4% and the NNTScope was <2. Compared with 50 ng ml(-1), up
      to 200 ng ml(-1) CRC miss rates remained at 16% (N=4). CONCLUSIONS: Cutoffs below
      the standard 100 ng ml(-1) resulted in not only higher detection rates of
      advanced lesions but also more colonoscopies. With sufficient capacity, 75 ng ml(
      1) might be advised; if not, up to 200 ng ml(-1) CRC miss rates are acceptable
      compared with the decrease in performed colonoscopies.

PMID- 19755998
TI  - Phase II trial of short-term neoadjuvant docetaxel and complete androgen blockade
      in high-risk prostate cancer.
AB  - BACKGROUND: The low probability of curing high-risk prostate cancer (PC) with
      local therapy suggests the need to study modality of therapeutic approaches. To
      this end, a prospective phase II trial of neoadjuvant docetaxel (D) and complete
      androgen blockade (CAB) was carried out in high-risk PC patients. The primary end
      point was to detect at least 10% of pCRs after chemohormonal treatment. METHODS:
      Patients with T1c-T2 clinical stage with prostate-specific antigen (PSA) >20 ng
      ml(-1) and/or Gleason score >or=7 (4+3) and T3 were included. Treatment consisted
      of three cycles of D 36 mg m(-2) on days 1, 8 and 15 every 28 days concomitant
      with CAB, followed by radical prostatectomy (RP). RESULTS: A total of 57 patients
      were included. Clinical stage was T1c, 11 patients (19.3%); T2, 30 (52.6%) and
      T3, 16 (28%) patients. Gleason score was >or=7 (4+3) in 44 (77%) patients and PSA
      >20 ng ml(-1) in 15 (26%) patients. Treatment was well tolerated with 51 (89.9%)
      patients completing neoadjuvant therapy together with RP. The rate of pCR was 6%
      (three patients). Three (6%) additional patients had microscopic residual tumour
      (near pCR) in prostate specimen. With a median follow-up of 35 months, 18 (31.6%)
      patients presented PSA relapse. CONCLUSION: Short-term neoadjuvant D and CAB
      induced a 6% pCR rate, which is close to what would be expected with ADT alone.
      The combination was generally well tolerated.

PMID- 19755999
TI  - Breast cancer: Improved care through effective management of febrile neutropenia.
      Foreword.

PMID- 19756000
TI  - Prevention of febrile neutropenia: use of prophylactic antibiotics.
AB  - Febrile neutropenia (FN) causes significant morbidity and mortality in patients
      receiving cytotoxic chemotherapy and can lead to reduced chemotherapy dose
      intensity and increased overall treatment costs. Antibiotic prophylaxis reduces
      the incidence of FN. Recent research and meta-analyses confirm that prophylactic
      fluoroquinolones decrease FN and infection-related mortality in patients with
      acute leukaemia and those receiving high-dose chemotherapy. Fluoroquinolone
      prophylaxis also lowers the incidence of FN and all-cause mortality following the
      first cycle of myelosuppressive chemotherapy for solid tumours. Levofloxacin has
      been the agent studied most thoroughly in this context. Although there is no
      convincing evidence that colonisation of individuals with resistant organisms due
      to antibiotic prophylaxis increases FN or mortality, such concerns must be taken
      seriously and the use of prophylaxis should be limited responsibly for patients
      with the greatest chance of benefit. Fluoroquinolone prophylaxis is well
      tolerated and cost-effective and should be offered to patients receiving
      chemotherapy for haematological malignancies and high-dose chemotherapy for solid
      tumours in which prolonged (>7 days) neutropenia is expected. It should also be
      considered for those receiving chemotherapy for solid tumours and lymphomas
      during the first cycle of chemotherapy when grade 4 neutropenia is anticipated.

PMID- 19756001
TI  - Prophylactic G-CSF in patients with early-stage breast cancer: a health economic
      review.
AB  - Although the use of prophylactic granulocyte colony-stimulating factor (G-CSF) in
      conjunction with myelosuppressive chemotherapy is supported by clinical research
      evidence and advocated by international clinical guidelines when the consequent
      risk of febrile neutropenia exceeds 20%, there remains doubt as to the cost
      effectiveness of the practice. There are limited economic data, and the data that
      are available are not necessarily applicable to the management of breast cancer
      in a European setting. Much of the available evidence on G-CSF in the management
      of febrile neutropenia is partial, focusing primarily on direct costs to the
      health service - that is, those related to hospitalisation and drug treatment. A
      full assessment of the cost effectiveness of G-CSF prophylaxis needs to take
      account of both costs and outcomes, including mortality, quality of life and
      patient functioning. As febrile neutropenia has been shown to affect
      productivity, consideration should also be given to quantifying the indirect
      costs of neutropenia.

PMID- 19756002
TI  - Management of chemotherapy-associated febrile neutropenia.
AB  - The development of febrile neutropenia during a course of chemotherapy is not
      only a life-threatening complication, it can also lead to a decision to reduce
      chemotherapy intensity in subsequent treatment cycles, thus putting patient
      outcomes at risk. Although there are strategies available for the primary
      prevention of febrile neutropenia, these are not widely used in the UK management
      of breast cancer. It is, therefore, paramount to have a well thought out and
      rigorously implemented care protocol for febrile neutropenia, involving patients,
      family/carers and health-care professionals in both primary and secondary care,
      to ensure early detection and effective management.

PMID- 19756003
TI  - Chemotherapy for early-stage breast cancer: a brief history.
AB  - The advent of chemotherapy for early-stage breast cancer has ushered in a new age
      of management for the condition. This article charts the evolution of
      chemotherapy for breast cancer, and highlights the current need for carefully
      planned, fully implemented local protocols to support the delivery of modern
      regimens.

PMID- 19756004
TI  - Impact of effective prevention and management of febrile neutropenia.
AB  - Chemotherapy-induced febrile neutropenia is costly in both financial and human
      terms. The associated costs can be reduced substantially through the development
      and implementation of national policies and locally agreed protocols for the
      prevention and management of febrile neutropenia. Patients, the NHS, healthcare
      professionals and the broader community all stand to benefit from a commitment to
      effective management of this common and predictable side effect of some
      chemotherapy regimens for early-stage breast cancer.

PMID- 19756005
TI  - Prevention of febrile neutropenia: use of granulocyte colony-stimulating factors.
AB  - There is good evidence to suggest that dose intensity is important when
      considering the effectiveness of adjuvant chemotherapy in patients with breast
      cancer. However, the development of chemotherapy-induced febrile neutropenia can
      lead to reduction in dose intensity and other treatment modifications, which may
      negatively affect patient outcomes. Febrile neutropenia can be prevented by the
      use of primary prophylactic treatment, notably with granulocyte colony
      stimulating factors. This practice is supported by international guidelines, all
      of which recommend that primary prophylaxis with granulocyte colony-stimulating
      factors should be used with chemotherapy where the risk of febrile neutropenia is
      20% or greater.

PMID- 19756006
TI  - Of trees and networks.

PMID- 19756007
TI  - Climate change and mutualism.

PMID- 19756008
TI  - Cholera transmission: the host, pathogen and bacteriophage dynamic.
AB  - Zimbabwe offers the most recent example of the tragedy that befalls a country and
      its people when cholera strikes. The 2008-2009 outbreak rapidly spread across
      every province and brought rates of mortality similar to those witnessed as a
      consequence of cholera infections a hundred years ago. In this Review we
      highlight the advances that will help to unravel how interactions between the
      host, the bacterial pathogen and the lytic bacteriophage might propel and quench
      cholera outbreaks in endemic settings and in emergent epidemic regions such as
      Zimbabwe.

PMID- 19756009
TI  - The structural biology of type IV secretion systems.
AB  - Type IV secretion systems (T4SSs) are versatile secretion systems that are found
      in both Gram-negative and Gram-positive bacteria and secrete a wide range of
      substrates, from single proteins to protein-protein and protein-DNA complexes.
      They usually consist of 12 components that are organized into ATP-powered, double
      membrane-spanning complexes. The structures of single soluble components or
      domains have been solved, but an understanding of how these structures come
      together has only recently begun to emerge. This Review focuses on the structural
      advances that have been made over the past 10 years and how the corresponding
      structural insights have helped to elucidate many of the details of the mechanism
      of type IV secretion.

PMID- 19756010
TI  - Engineering for biofuels: exploiting innate microbial capacity or importing
      biosynthetic potential?
AB  - The ideal microorganism for biofuel production will possess high substrate
      utilization and processing capacities, fast and deregulated pathways for sugar
      transport, good tolerance to inhibitors and product, and high metabolic fluxes
      and will produce a single fermentation product. It is unclear whether such an
      organism will be engineered using a native, isolated strain or a recombinant,
      model organism as the starting point. The choice between engineering natural
      function and importing biosynthetic capacity is affected by current progress in
      metabolic engineering and synthetic biology. This Review highlights some of the
      factors influencing the above decision, in light of current advances.

PMID- 19756011
TI  - Structural and mechanistic determinants of c-di-GMP signalling.
AB  - Bis-(3'-5')-cyclic dimeric GMP (c-di-GMP) is a ubiquitous second messenger that
      regulates cell surface-associated traits in bacteria. Components of this
      regulatory network include GGDEF and EAL domain-containing proteins that
      determine the cellular concentrations of c-di-GMP by mediating its synthesis and
      degradation, respectively. Crystal structure analyses in combination with
      functional studies have revealed the catalytic mechanisms and regulatory
      principles involved. Downstream, c-di-GMP is recognized by PilZ domain-containing
      receptors that can undergo large-scale domain rearrangements on ligand binding.
      Here, we review recent data on the structure and functional properties of the
      protein families that are involved in c-di-GMP signalling and discuss the
      mechanistic implications.

PMID- 19756012
TI  - Leptospira: the dawn of the molecular genetics era for an emerging zoonotic
      pathogen.
AB  - Leptospirosis is a zoonotic disease that has emerged as an important cause of
      morbidity and mortality among impoverished populations. One hundred years after
      the discovery of the causative spirochaetal agent, little is understood about
      Leptospira spp. pathogenesis, which in turn has hampered the development of new
      intervention strategies to address this neglected disease. However, the recent
      availability of complete genome sequences for Leptospira spp. and the discovery
      of genetic tools for their transformation have led to important insights into the
      biology of these pathogens and their pathogenesis. We discuss the life cycle of
      the bacterium, the recent advances in our understanding and the implications for
      the future prevention of leptospirosis.

PMID- 19756015
TI  - To sequence or not to sequence the whole-soil metagenome?

PMID- 19756013
TI  - Recombinational DNA repair in a cellular context: a search for the homology
      search.
AB  - Double-strand DNA breaks (DSBs) are the most detrimental lesion that can be
      sustained by the genetic complement, and their inaccurate mending can be just as
      damaging. According to the consensual view, precise DSB repair relies on
      homologous recombination. Here, we review studies on DNA repair, chromatin
      diffusion and chromosome confinement, which collectively imply that a genome-wide
      search for a homologous template, generally thought to be a pivotal stage in all
      homologous DSB repair pathways, is improbable. The implications of this assertion
      for the scope and constraints of DSB repair pathways and for the ability of
      diverse organisms to cope with DNA damage are discussed.

PMID- 19756016
TI  - Networking for BSL-3/4 laboratory scientist training.

PMID- 19756018
TI  - MR derived volumetric flow rate waveforms at locations within the common carotid,
      internal carotid, and basilar arteries.
AB  - The volumetric flow rate (VFR) waveform over the cardiac cycle in the cerebral
      vasculature is a significant factor in many studies, which involve
      cerebrovascular function. Perhaps contrary to expectation, the literature in this
      area is sparse and the characteristics of blood flow waveforms are ill defined. A
      better understanding of the variation of blood flow rate and pulsatility may aid
      our knowledge of risk factors involved in diseases and conditions, such as
      stroke, arteriovenous malformation, or aneurysm rupture. This study sought to
      characterise the blood flow waveform over the cardiac cycle at levels within the
      carotid artery and basilar artery (BA) in a normal cohort. The study cohort
      consisted of 22 subjects (recruitment age: 20 to 40 years) with no history of
      vascular disease (median age=26 years, interquartile range=25 to 32 years). Two
      dimensional quantitative phase-contrast magnetic resonance imaging was performed
      on each subject at nine anatomic locations within the carotid artery and BA.
      Significant differences in pulsatility were present within the carotid tree.
      Archetypal VFR waveforms were established for this group at the nine locations. A
      normal individual's VFR waveform at a location within the carotid tree can be
      estimated by taking the group's archetypal waveform for that location, and
      scaling by the individual's average flow rate.

PMID- 19756019
TI  - Improved measurement of drug exposure in the brain using drug-specific correction
      for residual blood.
AB  - A major challenge associated with the determination of the unbound brain-to
      plasma concentration ratio of a drug (K(p,uu,brain)), is the error associated
      with correction for the drug in various vascular spaces of the brain, i.e., in
      residual blood. The apparent brain vascular spaces of plasma water (V(water),
      10.3 microL/g brain), plasma proteins (V(protein), 7.99 microL/g brain), and the
      volume of erythrocytes (V(er), 2.13 microL/g brain) were determined and
      incorporated into a novel, drug-specific correction model that took the drug
      unbound fraction in the plasma (f(u,p)) into account. The correction model was
      successfully applied for the determination of K(p,uu,brain) for indomethacin,
      loperamide, and moxalactam, which had potential problems associated with
      correction. The influence on correction of the drug associated with erythrocytes
      was shown to be minimal. Therefore, it is proposed that correction for residual
      blood can be performed using an effective plasma space in the brain (V(eff)),
      which is calculated from the measured f(u,p) of the particular drug as well as
      from the estimates of V(water) and V(protein), which are provided in this study.
      Furthermore, the results highlight the value of determining K(p,uu,brain) with
      statistical precision to enable appropriate interpretation of brain exposure for
      drugs that appear to be restricted to the brain vascular spaces.

PMID- 19756020
TI  - Measurement error analysis for the determination of dopamine D(2) receptor
      occupancy using the agonist radioligand [(11)C]MNPA.
AB  - The purpose of this study is to investigate errors in quantitative analysis for
      estimating dopamine D(2) receptor occupancy of antipsychotics with agonist
      radioligand [(11)C]MNPA by numerical simulation, with particular attention to the
      validity of a quantitative approach based on the use of a reference region.
      Synthetic data were validated using clinical data combined with a bootstrap
      approach. Time-activity curves (TACs) of [(11)C]MNPA were simulated, and the
      reliability of binding potential (BP(ND)) and occupancy estimated by nonlinear
      least square (NLS) fitting and a simplified reference tissue model (SRTM) were
      investigated for various noise levels and scan durations. In the human positron
      emission tomography (PET) study with and without antipsychotic, risperidone, the
      uncertainty of BP(ND) and occupancy estimated by SRTM was investigated using
      resampled TACs based on bootstrap approach with weighted residual errors of
      fitting. For both NLS and SRTM, it was possible to have <3% of bias in occupancy
      estimates of [(11)C]MNPA by 60 mins. However, shortened scan duration degrades
      the quantification of very small binding potentials, especially in case of SRTM.
      Observations were replicated on the clinical data. Results showed that dopamine
      D(2) receptor occupancy by antipsychotics can be estimated precisely in region of
      interest analysis by SRTM with a longer than 60-min [(11)C]MNPA PET scan
      duration.

PMID- 19756022
TI  - High serum levels of growth factors are associated with good outcome in
      intracerebral hemorrhage.
AB  - In experimental models, growth factors (GFs) such as vascular endothelial growth
      factor (VEGF), Angiopoietin 1 (Ang-1), or granulocyte-colony stimulating factor
      (G-CSF) mediate brain recovery after intracerebral hemorrhage (ICH). Our aim was
      to study the association between serum levels of GF and clinical outcome in
      patients with ICH. A total of 95 patients with primary ICH (male, 66.3%; mean
      age, 67.8+/-9.8 years) were prospectively included in the study within 12 h from
      symptoms onset. The main outcome variable was good functional outcome at 3 months
      (modified Rankin scale < or =2). Median serum levels of GF at 72 h from stroke
      onset were significantly higher in patients with good outcome (n=39) compared
      with those with poor outcome (all P<0.0001). Serum levels of VEGF > or =330
      pg/mL, G-CSF > or =413 pg/mL, and Ang-1 > or =35 ng/mL at 72 h were independently
      associated with good functional outcome (odds ratio (OR), 11.2; 95% confidence
      interval (CI): 2.9 to 43.0; OR, 19.6; 95% CI: 3.9 to 97.9; and OR, 14.7; 95% CI:
      3.6 to 60.0, respectively), neurologic improvement (all P<0.0001) and reduced
      residual cavity at 3 months (all P<0.01). These results illustrate that high
      serum levels of GF are associated with good functional outcome and reduced lesion
      volume in ICH.

PMID- 19756021
TI  - Superparamagnetic iron oxide nanoparticles: diagnostic magnetic resonance imaging
      and potential therapeutic applications in neurooncology and central nervous
      system inflammatory pathologies, a review.
AB  - Superparamagnetic iron oxide nanoparticles have diverse diagnostic and potential
      therapeutic applications in the central nervous system (CNS). They are useful as
      magnetic resonance imaging (MRI) contrast agents to evaluate: areas of blood
      brain barrier (BBB) dysfunction related to tumors and other neuroinflammatory
      pathologies, the cerebrovasculature using perfusion-weighted MRI sequences, and
      in vivo cellular tracking in CNS disease or injury. Novel, targeted, nanoparticle
      synthesis strategies will allow for a rapidly expanding range of applications in
      patients with brain tumors, cerebral ischemia or stroke, carotid atherosclerosis,
      multiple sclerosis, traumatic brain injury, and epilepsy. These strategies may
      ultimately improve disease detection, therapeutic monitoring, and treatment
      efficacy especially in the context of antiangiogenic chemotherapy and
      antiinflammatory medications. The purpose of this review is to outline the
      current status of superparamagnetic iron oxide nanoparticles in the context of
      biomedical nanotechnology as they apply to diagnostic MRI and potential
      therapeutic applications in neurooncology and other CNS inflammatory conditions.

PMID- 19756023
TI  - Minocycline reduces neuronal death and attenuates microglial response after
      pediatric asphyxial cardiac arrest.
AB  - The mechanisms leading to delayed neuronal death after asphyxial cardiac arrest
      (ACA) in the developing brain are unknown. This study aimed at investigating the
      possible role of microglial activation in neuronal death in developing brain
      after ACA. Postnatal day-17 rats were subjected to 9 mins of ACA followed by
      resuscitation. Rats were randomized to treatment with minocycline, (90 mg/kg,
      intraperitoneally (i.p.)) or vehicle (saline, i.p.) at 1 h after return of
      spontaneous circulation. Thereafter, minocycline (22.5 mg/kg, i.p.) was
      administrated every 12 h until sacrifice. Microglial activation (evaluated by
      immunohistochemistry using ionized calcium-binding adapter molecule-1 (Iba1)
      antibody) coincided with DNA fragmentation and neurodegeneration in CA1
      hippocampus and cortex (assessed by deoxynucleotidyltransferase-mediated dUTP
      nick-end labeling (TUNEL), Fluoro-Jade-B and Nissl stain). Minocycline
      significantly decreased both the microglial response and neuronal degeneration
      compared with the vehicle. Asphyxial CA significantly enhanced proinflammatory
      cytokine and chemokine levels in hippocampus versus control (assessed by
      multiplex bead array assay), specifically tumor necrosis factor-alpha (TNF
      alpha), macrophage inflammatory protein-1alpha (MIP-1alpha), regulated upon
      activation, normal T-cell expressed and secreted (RANTES), and growth-related
      oncogene (GRO-KC) (P<0.05). Minocycline attenuated ACA-induced increases in MIP
      1alpha and RANTES (P<0.05). These data show that microglial activation and
      cytokine production are increased in immature brain after ACA. The beneficial
      effect of minocycline suggests an important role for microglia in selective
      neuronal death after pediatric ACA, and a possible therapeutic target.

PMID- 19756024
TI  - Glycaemic and insulinaemic properties of some German honey varieties.
AB  - The glycaemic and insulinaemic response to different German honey varieties have
      not been studied so far. Eight German honey grades differing in their floral
      source and carbohydrate composition were tested. Isoglucidic test meals (25 g
      carbohydrate) and a 25 g glucose reference were given to 10 clinically and
      metabolically healthy, fasting individuals (31.5+/-8.1 years of age (mean+/
      s.d.), two women). Glycaemic and insulinaemic index were calculated by the
      recommended FAO/WHO measure. Five of the eight tested honey varieties show a low
      glycaemic index below 55; for six of the eight tested varieties, the glycaemic
      load was lower than 10 (portion size of 20 g honey). Glycaemic index and
      insulinaemic index correlated significantly with the fructose content of honey
      varieties. The results show that glycaemic index and insulinaemic response depend
      on the fructose content of honey. Therefore, specific honey varieties may be
      recommended for subjects with impaired glucose tolerance instead of saccharose in
      food preparations.

PMID- 19756025
TI  - Glycaemic load is associated with insulin resistance in older Australian women.
AB  - BACKGROUND/OBJECTIVES: Diets with a high postprandial glycaemic response may
      contribute to the long-term development of insulin resistance and diabetes;
      however, earlier epidemiological studies are conflicting on whether glycaemic
      index (GI) or glycaemic load (GL) are dietary factors associated with the
      progression. Our objectives were to estimate GI and GL in a group of older women,
      and evaluate cross-sectional associations with insulin resistance.
      SUBJECTS/METHODS: The subjects were 329 Australian women aged 42-81 years
      participating in year 3 of the Longitudinal Assessment of Ageing in Women study.
      Dietary intakes were assessed by diet history interviews and analysed using a
      customized GI database. Insulin resistance was defined as a homeostasis model
      assessment value of >3.99, based on fasting blood glucose and insulin
      concentrations. RESULTS: GL was significantly higher in the 26 subjects who were
      classified as insulin resistant compared with subjects who were not (134+/-33
      versus 114+/-24, P<0.001). In a logistic regression model, an increment of 15 GL
      units increased the odds of insulin resistance by 2.09 (95% confidence interval
      (1.55, 2.80), P<0.001) independently of potential confounding variables. No
      significant associations were found when insulin resistance was assessed as a
      continuous variable. CONCLUSIONS: The results of this cross-sectional study
      support the concept that diets with a higher GL are associated with an increased
      risk of insulin resistance. Further studies are required to determine whether
      reducing the glycaemic intake, either by consuming lower GI foods or through
      smaller serves of carbohydrate, can contribute to a reduction in development of
      insulin resistance and long-term risk of type II diabetes.

PMID- 19756026
TI  - The association between maternal diet during pregnancy and bone mass of the
      children at age 16.
AB  - BACKGROUND/OBJECTIVES: Fetal life may be a critical period for the development
      and/or programming of metabolic systems, including the skeleton. However, it is
      unclear on the association between maternal nutrition during pregnancy and bone
      mass in their offspring at adolescence. SUBJECTS/METHODS: This was a birth cohort
      study of 216 adolescents (16.2+/-0.4 years). Dietary intake was measured by food
      frequency questionnaire. Bone densitometry was measured at the femoral neck,
      lumbar spine and total body by DXA. RESULTS: After adjustment for confounders,
      bone mineral density (BMD) of the femoral neck was positively associated with
      magnesium density and negatively associated with fat density (all P-values
      <0.05). BMD of the lumbar spine was positively associated with calcium, magnesium
      and phosphorus density and negatively associated with fat density (all P-values
      <0.05). Maternal milk intake was significantly positively associated with lumbar
      spine BMD. After considering all significant nutrients in the same model, fat
      density remained significant negatively for the femoral neck and lumbar spine,
      whereas magnesium density remained significant positively for the femoral neck.
      No nutrient was significant for the total body. CONCLUSIONS: Maternal intake of
      milk, fat and magnesium during the third trimester of pregnancy is predictive of
      BMD at age 16, suggesting that in utero diet influences peak bone mass possibly
      through programming bone responses.

PMID- 19756027
TI  - Nutrient intakes during diets including unkilned and large amounts of oats in
      celiac disease.
AB  - BACKGROUND/OBJECTIVES: We have shown earlier that consumption of moderate amount
      of oats improve intakes of vitamin B(1), fiber, magnesium and iron in celiac
      patients using gluten-free diet (GFD). The objective of this study was to clarify
      the effect of high amount of both kilned and unkilned oats on food and nutrient
      intakes in celiac patients in remission. Kilning as an industrial heating process
      is performed to preserve the main properties of oats and to lengthen its
      useableness. Kilning may, however, change the protein structure of oats and
      therefore influence on the intake of nutrients. SUBJECTS/METHODS: The study group
      consisted of 13 men and 18 women with celiac disease in remission. The patients
      who were earlier using moderate amount of oats as part of their GFD were
      randomized to consume kilned or unkilned oats. After 6 months, the patients
      changed the treatment groups. The goal of daily intake of oats was 100 g. Food
      records and frequency questionnaire were used to follow nutrient intakes.
      RESULTS: Type of oats did not affect the amount of oats used. In the group using
      kilned oats, the intake of vitamin B1 and magnesium and in the group of unkilned
      oats that of magnesium and zinc increased significantly during the first 6 months
      (P<or=0.05). CONCLUSIONS: :Large amounts of oats, both kilned and unkilned in
      GFD, can increase intakes of nutrients in celiac patients in remission. Oats
      improve the nutritional value of GFD.

PMID- 19756028
TI  - Nut consumption and risk of type II diabetes in the Physicians' Health Study.
AB  - BACKGROUND/OBJECTIVES: While type II diabetes (DM) is a major cause of morbidity
      in the United States, limited data are available on the association between nut
      intake and incident DM. We sought to examine the association between nut
      consumption and the risk of DM. SUBJECTS/METHODS: Prospective cohort of 20 224
      male participants of the Physicians' Health Study I. Nut consumption was
      estimated using a 19-item brief food frequency questionnaire, and incident DM was
      ascertained through yearly follow-up questionnaires. Cox regression was used to
      estimate relative risks of DM. RESULTS: The average age of the study participants
      was 54.4+/-9.4 years (range: 40.7-87.1). During a mean follow-up of 19.2 years,
      1828 cases of DM occurred. The crude incidence rates of DM were 4.82, 4.85, 4.92,
      4.16, 4.29 and 3.32 cases per 1000 person-years for individuals reporting nut
      consumption of rarely/never, <1, 1, 2-4, 5-6 and 7+ servings per week,
      respectively. While nut consumption was associated with a lower risk of DM in a
      model adjusted for age (P for tend 0.017), such relation was attenuated on
      additional control for other confounders (multivariable adjusted hazard ratios
      (95% confidence interval) for DM were 1.0 (reference), 1.06 (0.93-1.20), 1.10
      (0.95-1.26), 0.97 (0.82-1.14), 0.99 (0.76-1.30) and 0.87 (0.61-1.24) from the
      lowest to the highest category of nut consumption, respectively (P for trend
      0.99). No statistically significant association between nut consumption and DM
      was found in either lean or overweight/obese participants. CONCLUSIONS: Our data
      do not show an association between nut consumption and incident DM in US male
      physicians.

PMID- 19756029
TI  - A double-blind, placebo-controlled, randomized human study assessing the capacity
      of a novel galacto-oligosaccharide mixture in reducing travellers' diarrhoea.
AB  - BACKGROUND/OBJECTIVES: Prebiotics have attracted interest for their ability to
      positively affect the colonic microbiota composition, thus increasing resistance
      to infection and diarrhoeal disease. This study assessed the effectiveness of a
      prebiotic galacto-oligosaccharide mixture (B-GOS) on the severity and/or
      incidence of travellers' diarrhoea (TD) in healthy subjects. SUBJECTS/METHODS:
      The study was a placebo-controlled, randomized, double blind of parallel design
      in 159 healthy volunteers, who travelled for minimum of 2 weeks to a country of
      low or high risk for TD. The investigational product was the B-GOS and the
      placebo was maltodextrin. Volunteers were randomized into groups with an equal
      probability of receiving either the prebiotic or placebo. The protocol comprised
      of a 1 week pre-holiday period recording bowel habit, while receiving
      intervention and the holiday period. Bowel habit included the number of bowel
      movements and average consistency of the stools as well as occurrence of
      abdominal discomfort, flatulence, bloating or vomiting. A clinical report was
      completed in the case of diarrhoeal incidence. A post-study questionnaire was
      also completed by all subjects on their return. RESULTS: Results showed
      significant differences between the B-GOS and the placebo group in the incidence
      (P<0.05) and duration (P<0.05) of TD. Similar findings occurred on abdominal pain
      (P<0.05) and the overall quality of life assessment (P<0.05). CONCLUSIONS:
      Consumption of the tested galacto-oligosaccharide mixture showed significant
      potential in preventing the incidence and symptoms of TD.

PMID- 19756030
TI  - Evaluation of a novel food composition database that includes glutamine and other
      amino acids derived from gene sequencing data.
AB  - OBJECTIVES: To determine the content of glutamine in major food proteins.
      SUBJECTS/METHODS: We used a validated 131-food item food frequency questionnaire
      (FFQ) to identify the foods that contributed the most to protein intake among
      70,356 women in the Nurses' Health Study (NHS, 1984). The content of glutamine
      and other amino acids in foods was calculated based on protein fractions
      generated from gene sequencing methods (Swiss Institute of Bioinformatics) and
      compared with data from conventional (USDA) and modified biochemical (Khun)
      methods. Pearson correlation coefficients were used to compare the participants'
      dietary intakes of amino acids by sequencing and USDA methods. RESULTS: The
      glutamine content varied from 0.01 to to 9.49 g/100 g of food and contributed
      from 1 to to 33% of total protein for all FFQ foods with protein. When comparing
      the sequencing and Kuhn's methods, the proportion of glutamine in meat was 4.8 vs
      4.4%. Among NHS participants, mean glutamine intake was 6.84 (s.d.=2.19) g/day
      and correlation coefficients for amino acid between intakes assessed by
      sequencing and USDA methods ranged from 0.94 to 0.99 for absolute intake, -0.08
      to 0.90 after adjusting for 100 g of protein, and 0.88 to 0.99 after adjusting
      for 1000 kcal. The between-person coefficient of variation of energy-adjusted
      intake of glutamine was 16%. CONCLUSIONS: These data suggest that (1) glutamine
      content can be estimated from gene sequencing methods and (2) there is a
      reasonably wide variation in energy-adjusted glutamine intake, allowing for
      exploration of glutamine consumption and disease.

PMID- 19756031
TI  - Obesity, coffee consumption and CRP levels in postmenopausal overweight/obese
      women: importance of hormone replacement therapy use.
AB  - BACKGROUND/OBJECTIVES: Obesity is associated with an inflammatory state that is
      often characterized by elevated plasma C-reactive protein (CRP) levels. Although
      coffee is broadly consumed in Western societies, few studies have examined the
      relationship between obesity, coffee consumption and CRP levels. The objective of
      this study was to assess the relationship between obesity, coffee consumption and
      variation in CRP in postmenopausal, overweight/obese women with or without
      hormone replacement therapy (HRT) use. SUBJECTS/METHODS: Cross-sectional analyses
      of 344 healthy sedentary, overweight/obese postmenopausal women (mean age=57.1+/
      6.4 years and mean body mass index (BMI)=36.1+/-3.9 kg/ m(2)). Plasma CRP levels
      were measured by a highly sensitive immunoassay that used monoclonal antibodies
      coated with polystyrene particles. Diet was assessed using the Food Intake and
      Analysis System semiquantitative food frequency questionnaire. RESULTS: Plasma
      CRP was positively associated with BMI (P<0.001) and negatively associated with
      coffee consumption (P<or=0.05). In women using HRT, plasma CRP was positively
      associated with BMI in women consuming less than one cup of coffee per month (r
      (2)=0.15 (P<0.001)), one cup per day (0.14 (P=0.02)) and more than one cup per
      day (0.12 (P=0.03)). In women who did not use HRT, CRP was associated with BMI
      only in women consuming less than one cup of coffee per day (r (2)=0.16
      (P<0.001)) but not in women consuming one cup per day (0.06 (P=0.10)) or more
      than one daily cup of coffee (0.03 (P=0.27)). CONCLUSIONS: Among overweight/obese
      postmenopausal women, coffee consumption is negatively associated with CRP.
      Coffee consumption appears to attenuate the association between BMI and CRP, but
      only in women not using HRT.

PMID- 19756032
TI  - Development of a 20-item food frequency questionnaire to assess a 'prudent'
      dietary pattern among young women in Southampton.
AB  - OBJECTIVE: To develop a short food frequency questionnaire (FFQ) that can be used
      among young women in Southampton to assess compliance with a prudent dietary
      pattern characterized by high consumption of wholemeal bread, fruit and
      vegetables, and low consumption of sugar, white bread, and red and processed
      meat. METHODS: Diet was assessed using a 100-item interviewer-administered FFQ in
      6129 non-pregnant women aged 20-34 years. In total, 94 of these women were re
      interviewed 2 years later using the same FFQ. Subsequently, diet was assessed in
      378 women attending SureStart Children's Centres in the Nutrition and Well-being
      Study (NWS) using a 20-item FFQ. The 20 foods included were those that
      characterized the prudent dietary pattern. RESULTS: The 20-item prudent diet
      score was highly correlated with the full 100-item score (r=0.94) in the
      Southampton Women's Survey (SWS). Both scores were correlated with red blood cell
      folate (r=0.28 for the 100-item score and r=0.25 for the 20-item score). Among
      the women re-interviewed after 2 years, the change in prudent diet score was
      correlated with change in red cell folate for both the 20-item (r(S)=0.31) and
      100-item scores (r(S)=0.32). In the NWS a strong association between the 20-item
      prudent diet score and educational attainment (r=0.41) was observed, similar to
      that seen in the SWS (r=0.47). CONCLUSIONS: The prudent diet pattern describes a
      robust axis of variation in diet. A 20-item FFQ based on the foods that
      characterize the prudent diet pattern has clear advantages in terms of time and
      resources, and is a helpful tool to characterize the diets of young women in
      Southampton.

PMID- 19756033
TI  - Accuracy of children's school-breakfast reports and school-lunch reports (in 24-h
      dietary recalls) differs by retention interval.
AB  - BACKGROUND/OBJECTIVES: Validation-study data were analyzed to investigate the
      effect of retention interval (time between the to-be-reported meal and interview)
      on accuracy of children's school-breakfast reports and school-lunch reports in 24
      h recalls, and to compare accuracy of children's school-breakfast reports for two
      breakfast locations (classroom; cafeteria). SUBJECTS/METHODS: Each of 374 fourth
      grade children was interviewed to obtain a 24-h recall using one of six
      conditions from crossing two target periods (prior 24 h; previous day) with three
      interview times (morning; afternoon; evening). Each condition had 62 or 64
      children (half boys). A recall's target period included one school breakfast and
      one school lunch, for which the child had been observed. Food-item variables
      (observed number; reported number; omission rate; intrusion rate) and energy
      variables (observed; reported; report rate; correspondence rate; inflation ratio)
      were calculated for each child for school breakfast and school lunch separately.
      RESULTS: Accuracy for school-breakfast reports and school-lunch reports was
      inversely related to retention interval. Specifically, as indicated by smaller
      omission rates, smaller intrusion rates, larger correspondence rates and smaller
      inflation ratios, accuracy for school-breakfast reports was best for prior-24-h
      recalls in the morning, and accuracy for school-lunch reports was best for prior
      24-h recalls in the afternoon. For neither school meal was a significant sex
      effect found for any variable. For school-breakfast reports, there was no
      significant school-breakfast location effect for any variable. CONCLUSIONS: By
      shortening the retention interval, accuracy can be improved for school-breakfast
      reports and school-lunch reports in children's 24-h recalls.

PMID- 19756034
TI  - Faecal varieties between high- and low-converters of cholesterol.
AB  - BACKGROUND: Analyzing faecal sterol concentrations in humans, subjects with a
      strongly decreased faecal cholesterol conversion were identified. The reasons and
      outcomes of this phenomenon have not been sufficiently investigated because of
      the complexity of the host-microflora interactions. SUBJECTS/METHODS: To evaluate
      differences between cholesterol high and low converters, the sterol excretion and
      faeces attributes of 320 healthy subjects (213 women, 107 men) were analyzed. Two
      different cut-off levels classifying cholesterol high and low converters were
      tested (level 1: conversion rate <30%; level 2: 50th percentile). RESULTS: In
      both test models the faeces attributes differ significantly in a lower pH value
      and a lower faecal dry matter of the low converters in comparison with the high
      converters. CONCLUSIONS: These findings in faeces may reflect the conditions in
      the colon and can be a reason for the decreased bacterial growth and/or activity
      of cholesterol-reducing bacteria in the colonic microflora.

PMID- 19756035
TI  - Anthropometric, metabolic, dietary and psychosocial profiles of underreporters of
      energy intake: a doubly labeled water study among overweight/obese postmenopausal
      women--a Montreal Ottawa New Emerging Team study.
AB  - BACKGROUND/OBJECTIVES: To analyze the anthropometric, metabolic, psychosocial and
      dietary profiles of underreporters, identified by the doubly labeled water
      technique, in a well-characterized population of overweight and obese
      postmenopausal women. SUBJECTS/METHODS: The study population consisted of 87
      overweight and obese sedentary postmenopausal women (age: 57.7+/-4.8 years, body
      mass index: 32.4+/-4.6 kg/m(2)). Subjects were identified as underreporters based
      on the energy intake to energy expenditure ratio of <0.80. We measured (1) body
      composition (by dual-energy X-ray absorptiometry), (2) visceral fat (by computed
      tomography), (3) blood profile, (4) resting blood pressure, (5) peak oxygen
      consumption (VO(2 peak)), (6) total energy expenditure, (7) muscle strength and
      (8) psychosocial and dietary profiles. RESULTS: Out of 87 subjects, 50 (57.5%)
      were identified as underreporting subjects in our cohort. Underreporters showed
      higher levels of body mass index, fat mass, visceral fat, hsC-reactive protein,
      perceived stress and percentage of energy from protein, as well as lower levels
      of VO(2 peak), dietary intake of calcium, fiber, iron, vitamin B-1 and 6, as well
      as servings of fruit and vegetables. Logistic regression analysis showed that fat
      mass, odd ratio 1.068 (95% confidence interval 1.009-1.130) and perceived stress,
      odd ratio 1.084 (95% confidence interval 1.011-1.162) were independent
      characteristics of underreporters. CONCLUSIONS: Results from this study show
      significant differences in anthropometric, metabolic, psychosocial and dietary
      profiles between underreporters and non-underreporters in our cohort of
      overweight and obese postmenopausal women.

PMID- 19756036
TI  - The worm in the fruit of the mitochondrial DNA tree.

PMID- 19756037
TI  - How fat is the tail?

PMID- 19756038
TI  - A sex-determining region on the Y chromosome controls the sex-reversal ratio in
      interspecific hybrids between Oryzias curvinotus females and Oryzias latipes
      males.
AB  - Oryzias latipes and Oryzias curvinotus are closely related medaka species that
      have the common sex-determining gene, DMY, on their homologous Y chromosomes. We
      previously reported that sex-reversed XY females were produced in hybrids between
      O. curvinotus females and O. latipes males (Hd-rR inbred strain). In this study
      we used HNI inbred strain males of O. latipes for mating with O. curvinotus
      females, and found that all the XY hybrids developed as males. To map the factor
      responsible for this strain-specific XY sex reversal, O. curvinotus females were
      mated with two Y-congenic strains (HNI.Y(Hd-rR) and Hd-rR.Y(HNI)) and a
      recombinant congenic strain (Hd-rR.Y(HNI)rr). HNI.Y(Hd-rR) produced sex-reversed
      females in the XY hybrids, whereas no sex-reversed females were obtained in the
      XY hybrids from Hd-rR.Y(HNI) and Hd-rR.Y(HNI)rr, demonstrating that a small
      region on the Y chromosome, which includes DMY, is responsible for the XY sex
      reversal. Sex-reversed hybrids were only produced in the presence of the Y
      chromosomal region derived from the Hd-rR strain, suggesting that missense or
      regulatory mutations specific to the Hd-rR Y-chromosomal region induce the sex
      reversal.

PMID- 19756039
TI  - Chromosomal mapping of repetitive DNAs in the beetle Dichotomius geminatus
      provides the first evidence for an association of 5S rRNA and histone H3 genes in
      insects, and repetitive DNA similarity between the B chromosome and A complement.
AB  - Chromosomal banding techniques and repetitive DNA mapping are useful tools in
      comparative analysis and in the elucidation of genome organization of several
      groups of eukaryotes. In this study, we contributed to the knowledge of
      Coleoptera genomes by reporting the chromosomal organization of repetitive DNA
      sequences, as well as the presence and characteristics of a B chromosome in two
      natural populations of Dichotomius geminatus (Coleoptera; Scarabaeidae) using
      classical, chromosomal banding and molecular cytogenetic techniques. As in other
      coleopteran species, the heterochromatin was mainly concentrated in
      pericentromeric regions and the B chromosome was composed almost entirely of
      heterochromatin. Physical mapping using double fluorescent in situ hybridization
      was performed for the first time in Coleoptera; using DNA probes for 5S and 18S
      ribosomal RNA (rRNA) and histone H3 genes, we showed that ribosomal 18S rDNAs are
      located in chromosomes 3 and 4, whereas 5S rRNA and histone H3 genes are
      colocalized in chromosomal pair 2 and show an apparently interspersed
      organization. Moreover, these genes are not present in the B chromosome,
      suggesting that the B chromosome did not originate from chromosomal pairs 2, 3 or
      4. On the other hand, mapping of the C(0)t-1 DNA fraction showed that the B
      chromosome is enriched in repetitive DNA elements, also present in the standard
      complement, indicating an intraspecific origin of this element in D. geminatus.
      These results will contribute to our understanding of genome organization and
      evolution of repetitive elements in Coleoptera and other insects regarding both A
      and B chromosomes.

PMID- 19756040
TI  - Structural and functional constraints in the evolution of protein families.
AB  - High-throughput genomic sequencing has focused attention on understanding
      differences between species and between individuals. When this genetic variation
      affects protein sequences, the rate of amino acid substitution reflects both
      Darwinian selection for functionally advantageous mutations and selectively
      neutral evolution operating within the constraints of structure and function.
      During neutral evolution, whereby mutations accumulate by random drift, amino
      acid substitutions are constrained by factors such as the formation of
      intramolecular and intermolecular interactions and the accessibility to water or
      lipids surrounding the protein. These constraints arise from the need to conserve
      a specific architecture and to retain interactions that mediate functions in
      protein families and superfamilies.

PMID- 19756041
TI  - Sampling scheme for pyrethroids on multiple surfaces on commercial aircrafts.
AB  - A wipe sampler for the collection of permethrin from soft and hard surfaces has
      been developed for use in aircraft. "Disinsection" or application of pesticides,
      predominantly pyrethrods, inside commercial aircraft is routinely required by
      some countries and is done on an as-needed basis by airlines resulting in
      potential pesticide dermal and inhalation exposures to the crew and passengers. A
      wipe method using filter paper and water was evaluated for both soft and hard
      aircraft surfaces. Permethrin was analyzed by GC/MS after its ultrasonication
      extraction from the sampling medium into hexane and volume reduction. Recoveries,
      based on spraying known levels of permethrin, were 80-100% from table trays, seat
      handles and rugs; and 40-50% from seat cushions. The wipe sampler is easy to use,
      requires minimum training, is compatible with the regulations on what can be
      brought through security for use on commercial aircraft, and readily adaptable
      for use in residential and other settings.

PMID- 19756042
TI  - The use of alternative pollutant metrics in time-series studies of ambient air
      pollution and respiratory emergency department visits.
AB  - Various temporal metrics of daily pollution levels have been used to examine the
      relationships between air pollutants and acute health outcomes. However, daily
      metrics of the same pollutant have rarely been systematically compared within a
      study. In this analysis, we describe the variability of effect estimates
      attributable to the use of different temporal metrics of daily pollution levels.
      We obtained hourly measurements of ambient particulate matter (PM2.5), carbon
      monoxide (CO), nitrogen dioxide (NO2), and ozone (O3) from air monitoring
      networks in 20-county Atlanta for the time period 1993-2004. For each pollutant,
      we created (1) a daily 1-h maximum; (2) a 24-h average; (3) a commute average;
      (4) a daytime average; (5) a nighttime average; and (6) a daily 8-h maximum (only
      for O3). Using Poisson generalized linear models, we examined associations
      between daily counts of respiratory emergency department visits and the previous
      day's pollutant metrics. Variability was greatest across O3 metrics, with the 8-h
      maximum, 1-h maximum, and daytime metrics yielding strong positive associations
      and the nighttime O3 metric yielding a negative association (likely reflecting
      confounding by air pollutants oxidized by O3). With the exception of daytime
      metric, all of the CO and NO2 metrics were positively associated with respiratory
      emergency department visits. Differences in observed associations with
      respiratory emergency room visits among temporal metrics of the same pollutant
      were influenced by the diurnal patterns of the pollutant, spatial
      representativeness of the metrics, and correlation between each metric and
      copollutant concentrations. Overall, the use of metrics based on the US National
      Ambient Air Quality Standards (for example, the use of a daily 8-h maximum O3 as
      opposed to a 24-h average metric) was supported by this analysis. Comparative
      analysis of temporal metrics also provided insight into underlying relationships
      between specific air pollutants and respiratory health.

PMID- 19756043
TI  - A simple and efficient algorithm for genome-wide homozygosity analysis in
      disease.
AB  - Here we propose a simple statistical algorithm for rapidly scoring loci
      associated with disease or traits due to recessive mutations or deletions using
      genome-wide single nucleotide polymorphism genotyping case-control data in
      unrelated individuals. This algorithm identifies loci by defining homozygous
      segments of the genome present at significantly different frequencies between
      cases and controls. We found that false positive loci could be effectively
      removed from the output of this procedure by applying different physical size
      thresholds for the homozygous segments. This procedure is then conducted
      iteratively using random sub-datasets until the number of selected loci
      converges. We demonstrate this method in a publicly available data set for
      Alzheimer's disease and identify 26 candidate risk loci in the 22 autosomes. In
      this data set, these loci can explain 75% of the genetic risk variability of the
      disease.

PMID- 19756044
TI  - Evidence for a major role of antisense RNAs in cyanobacterial gene regulation.
AB  - Information on the numbers and functions of naturally occurring antisense RNAs
      (asRNAs) in eubacteria has thus far remained incomplete. Here, we screened the
      model cyanobacterium Synechocystis sp. PCC 6803 for asRNAs using four different
      methods. In the final data set, the number of known noncoding RNAs rose from 6
      earlier identified to 60 and of asRNAs from 1 to 73 (28 were verified using at
      least three methods). Among these, there are many asRNAs to housekeeping,
      regulatory or metabolic genes, as well as to genes encoding electron transport
      proteins. Transferring cultures to high light, carbon-limited conditions or
      darkness influenced the expression levels of several asRNAs, suggesting their
      functional relevance. Examples include the asRNA to rpl1, which accumulates in a
      light-dependent manner and may be required for processing the L11 r-operon and
      the SyR7 noncoding RNA, which is antisense to the murF 5' UTR, possibly
      modulating murein biosynthesis. Extrapolated to the whole genome, approximately
      10% of all genes in Synechocystis are influenced by asRNAs. Thus, chromosomally
      encoded asRNAs may have an important function in eubacterial regulatory networks.

PMID- 19756045
TI  - Systematic phenome analysis of Escherichia coli multiple-knockout mutants reveals
      hidden reactions in central carbon metabolism.
AB  - Central carbon metabolism is a basic and exhaustively analyzed pathway. However,
      the intrinsic robustness of the pathway might still conceal uncharacterized
      reactions. To test this hypothesis, we constructed systematic multiple-knockout
      mutants involved in central carbon catabolism in Escherichia coli and tested
      their growth under 12 different nutrient conditions. Differences between in
      silico predictions and experimental growth indicated that unreported reactions
      existed within this extensively analyzed metabolic network. These putative
      reactions were then confirmed by metabolome analysis and in vitro enzymatic
      assays. Novel reactions regarding the breakdown of sedoheptulose-7-phosphate to
      erythrose-4-phosphate and dihydroxyacetone phosphate were observed in
      transaldolase-deficient mutants, without any noticeable changes in gene
      expression. These reactions, triggered by an accumulation of sedoheptulose-7
      phosphate, were catalyzed by the universally conserved glycolytic enzymes ATP
      dependent phosphofructokinase and aldolase. The emergence of an alternative
      pathway not requiring any changes in gene expression, but rather relying on the
      accumulation of an intermediate metabolite may be a novel mechanism mediating the
      robustness of these metabolic networks.

PMID- 19756046
TI  - Disease signatures are robust across tissues and experiments.
AB  - Meta-analyses combining gene expression microarray experiments offer new insights
      into the molecular pathophysiology of disease not evident from individual
      experiments. Although the established technical reproducibility of microarrays
      serves as a basis for meta-analysis, pathophysiological reproducibility across
      experiments is not well established. In this study, we carried out a large-scale
      analysis of disease-associated experiments obtained from NCBI GEO, and evaluated
      their concordance across a broad range of diseases and tissue types. On
      evaluating 429 experiments, representing 238 diseases and 122 tissues from 8435
      microarrays, we find evidence for a general, pathophysiological concordance
      between experiments measuring the same disease condition. Furthermore, we find
      that the molecular signature of disease across tissues is overall more prominent
      than the signature of tissue expression across diseases. The results offer new
      insight into the quality of public microarray data using pathophysiological
      metrics, and support new directions in meta-analysis that include
      characterization of the commonalities of disease irrespective of tissue, as well
      as the creation of multi-tissue systems models of disease pathology using public
      data.

PMID- 19756047
TI  - Global analysis of the glycoproteome in Saccharomyces cerevisiae reveals new
      roles for protein glycosylation in eukaryotes.
AB  - To further understand the roles of protein glycosylation in eukaryotes, we
      globally identified glycan-containing proteins in yeast. A fluorescent lectin
      binding assay was developed and used to screen protein microarrays containing
      over 5000 proteins purified from yeast. A total of 534 yeast proteins were
      identified that bound either Concanavalin A (ConA) or Wheat-Germ Agglutinin
      (WGA); 406 of them were novel. Among the novel glycoproteins, 45 were validated
      by mobility shift upon treatment with EndoH and PNGase F, thereby extending the
      number of validated yeast glycoproteins to 350. In addition to many components of
      the secretory pathway, we identified other types of proteins, such as
      transcription factors and mitochondrial proteins. To further explore the role of
      glycosylation in mitochondrial function, the localization of four mitochondrial
      proteins was examined in the presence and absence of tunicamycin, an inhibitor of
      N-linked protein glycosylation. For two proteins, localization to the
      mitochondria is diminished upon tunicamycin treatment, indicating that protein
      glycosylation is important for protein function. Overall, our studies greatly
      extend our understanding of protein glycosylation in eukaryotes through the
      cataloguing of glycoproteins, and describe a novel role for protein glycosylation
      in mitochondrial protein function and localization.

PMID- 19756048
TI  - Engineering the Salmonella type III secretion system to export spider silk
      monomers.
AB  - The type III secretion system (T3SS) exports proteins from the cytoplasm, through
      both the inner and outer membranes, to the external environment. Here, a system
      is constructed to harness the T3SS encoded within Salmonella Pathogeneity Island
      1 to export proteins of biotechnological interest. The system is composed of an
      operon containing the target protein fused to an N-terminal secretion tag and its
      cognate chaperone. Transcription is controlled by a genetic circuit that only
      turns on when the cell is actively secreting protein. The system is refined using
      a small human protein (DH domain) and demonstrated by exporting three silk
      monomers (ADF-1, -2, and -3), representative of different types of spider silk.
      Synthetic genes encoding silk monomers were designed to enhance genetic stability
      and codon usage, constructed by automated DNA synthesis, and cloned into the
      secretion control system. Secretion rates up to 1.8 mg l(-1) h(-1) are
      demonstrated with up to 14% of expressed protein secreted. This work introduces
      new parts to control protein secretion in Gram-negative bacteria, which will be
      broadly applicable to problems in biotechnology.

PMID- 19756049
TI  - [When the starting point is the craziest...].

PMID- 19756050
TI  - [Mysteries of the sleep].

PMID- 19756051
TI  - [Drug management in children and the elderly].

PMID- 19756052
TI  - [Pharmacotherapy in nursing homes].
AB  - BACKGROUND: There is a high risk of drug-related problems in nursing homes due to
      polypharmacy, multi-morbidity and age-related changes. We describe the drug use
      and compare the pharmacotherapy in two nursing homes with different staffing of
      physicians. MATERIAL AND METHODS: We included 48 long-term patients from two
      nursing homes in Oslo; i.e. nursing home A (24 patients) and nursing home B (24
      patients). A pharmacist recorded information on patients' drug use, identified
      and classified drug-related problems, and classified the drugs used according to
      their anticholinergic burden. Two physicians (with experience in geriatrics and
      nursing home medicine) assessed the clinical importance of the drug-related
      problems independently from each other. The physicians were blinded with respect
      to which nursing home the patients came from. RESULTS: Patients in nursing home A
      used a median (interquartile range [IQR]) of 7.0 (5.3-11.0) drugs, and those in
      nursing home B used 9.5 (8.0-12.8); the median difference was 2.0, 95% CI 1.0
      4.0, p = 0.006). Patients also had lower anticholinergic drug scores in nursing
      home A (1.0 [0.0-2.0]) than in nursing home B (2.0 [2.0-3.8]); median difference
      1.0, 95% CI 0.0-2.0, p = 0.009). Patients in home A also had lower numbers of
      drug-related problems (3.0 [2.0-4.0]) than those in home B (5.5 [3.3-8.0]);
      median difference 1.0, 85% CI 0.0-3.0, p = 0.007. No significant differences were
      found between the nursing homes with regard to patients' age, co-morbidity,
      kidney function, or dementia state, but nursing home A had a better staffing of
      physicians. INTERPRETATION: The number of drugs used as well as the quality
      indicators varied considerably between the nursing homes assessed. Differences in
      physician staffing might be one reasonable explanation. Our study highlights the
      importance of systematic multidisciplinary medication reviews for quality
      improvement in nursing homes.

PMID- 19756053
TI  - [Disease caused by the new influenza A(H1N1) virus].
AB  - BACKGROUND: A new A(H1N1) influenza virus was detected in April 2009. The virus
      is now causing a pandemic of influenza. The article presents an overview of
      symptoms, complications, vulnerable groups, diagnosis and treatment. MATERIAL AND
      METHODS: The overview is based on literature identified through a search in
      PubMed (using PubMed's own search strategy) and on official reports from WHO and
      the disease control centres of EU and the USA. RESULTS: The new influenza A(H1N1)
      has so far mainly affected young people, only few people over 60 years. The
      clinical presentation is similar to that of ordinary influenza; but nausea,
      vomiting and diarrhoea seem to be more common. The reported risk of complications
      and case fatality are low, but hospitalisation, pneumonia and deaths have
      occurred, also in previously healthy young individuals. Antiviral treatment with
      oseltamivir or zanamivir is likely to be as effective as in ordinary influenza.
      INTERPRETATION: Mild cases may be underrepresented in the published literature.
      It is important to keep up-to-date on international reports on the nature of the
      disease in order to best prepare clinicians to diagnose and treat patients when
      the epidemic hits Norway with full force.

PMID- 19756054
TI  - [Effects of antihypertensive drugs on glucose metabolism and cardiovascular
      events].
AB  - BACKGROUND: Diuretics and beta-blockers (conventional antihypertensive therapy)
      may increase the level of blood glucose. Such an increase could enhance the risk
      of cardiovascular events and have an unfavourable effect on prognosis, but
      available documentation is not conclusive. MATERIAL AND METHOD: The material
      consists of literature collected over many years, supplemented with literature
      retrieved through an extensive search (non-systematic) in Pubmed. RESULTS:
      Several studies, of 4-6 years duration, have shown that conventional therapy
      induces a small increase of blood glucose without increasing cardiovascular
      events. Newer antihypertensive drugs (angiotensin converting enzyme (ACE)
      inhibitors, angiotensin II (AII)- receptor blockers and calcium blockers) do not
      have this effect. Conventional therapy can also prevent cardiovascular events in
      patients with diabetes. Several studies on hypertension have shown that drugs'
      ability to reduce blood pressure is most decisive for their prevention of events.
      INTERPRETATION: In most cases, diuretics and beta-blockers are as effective as
      the newer antihypertensives, but drugs with an effect on the renin-angiotensin
      system are usually preferred as first choice in patients with diabetes. However,
      when several drugs must be combined in order to achieve the blood pressure goal
      in diabetic patients (< 130/80 mm Hg), diuretics and beta-blockers may be
      administered.

PMID- 19756055
TI  - [Clinical pharmacist in a multidisciplinary team in a paediatric department].
AB  - BACKGROUND: Clinical pharmacists have not been a part of multidisciplinary teams
      at Rikshospitalet, University Hospital, Norway, which is in contrast with common
      practice in other countries. We wanted to investigate how such specialists could
      contribute to quality assurance of drug treatment in a paediatric ward. MATERIAL
      AND METHOD: A clinical pharmacist reviewed medical charts from patients admitted
      to the paediatric ward at Rikshospitalet in the period 1.2.2006-31.3.2007. Drug
      related problems (DRP), identified by the pharmacist, were discussed with
      physicians and nurses before the ward round. In the period 31.7.2006-31.3.2007,
      DRPs were recorded on a quantitative and qualitative level. Nurses and physicians
      evaluated the project by responding to a questionnaire. RESULTS AND
      INTERPRETATION: The pharmacist identified 137 DRPs in 103 of the 384 screened
      charts. Immediate action was taken in 73 of the 137 cases, 39 DRP were considered
      relevant, but without requiring action, and 25 of the DRP recordings had no
      consequence for the treatment. The most commented DRPs were "dosage" (n = 48),
      "drug choice" (n = 35) and "need for monitoring" (n = 32). The pharmacist
      responded to DRPs, educated nurses, developed internal guidelines and recommended
      cost-saving measures. Seven of eight doctors and all the 15 nurses thought that
      the ward had benefited from the pharmacist's contribution. Interpretation.
      Clinical pharmacists may make a positive contribution to quality assurance of
      drug treatment in hospital wards.

PMID- 19756056
TI  - [Use of psychotropic medication among individuals with mental retardation].
AB  - BACKGROUND: Individuals who have mental retardation and live by themselves have
      little knowledge of psychotropic medication. The aim of this study is to examine
      the use of psychotropic medication among individuals with mental retardation, 10
      20 years after they moved from institutionalised to open care. MATERIAL AND
      METHODS: 116 individuals with mental retardation, who had moved from one specific
      institution to open care (in their own homes) in the period 1984-94, were
      included in the study. Data were collected from medical records, and from
      interviews with a caregiver. RESULTS: 50 (43%) individuals used psychotropic
      drugs at the time of recording. It was common to use combinations of psychotropic
      drugs; 37 used antipsychotics, nine used antidepressants and 14 used anxiolytics.
      Information on the degree of retardation was not available for all individuals;
      but 20 of the 28 who used antipsychotics had serious mental retardation, while
      eight had a mild or moderate degree of mental retardation (p < 0.001). No
      statistically significant association was found between degree of retardation and
      use of antidepressants and anxiolytics. Only 14 (27%) of those who used
      psychotropic drugs had a psychiatric diagnosis. The drugs were usually prescribed
      by a regular general practitioner. INTERPRETATION: Individuals with mental
      retardation use psychotropic medication extensively. Caregivers' insufficient
      knowledge on how to apply non-pharmacological intervention may be an explanation
      for the extensive use of psychotropic drugs in treatment of challenging
      behaviour.

PMID- 19756057
TI  - [From tonsillitis to coxitis].
AB  - We present a 19-year-old woman with a throat infection, increased temperature, a
      positive mononucleosis monospot test and clinical signs of a lower respiratory
      tract infection. The diagnosis was thought to be mononucleosis complicated by
      bacterial pneumonia, but she was later found to have Fusobacterium necrophorum in
      blood cultures. She subsequently developed metastatic abscesses in her lungs and
      hip joint and was diagnosed with Lemierre's Syndrome. This case report highlights
      the importance of close links between clinicians and microbiologists in order to
      prevent morbidity and mortality in patients with an infectious disease.

PMID- 19756058
TI  - [An underestimated throat bacteria].

PMID- 19756059
TI  - [Basic sleep mechanisms].
AB  - BACKGROUND: Sleep problems are a frequent cause for contacting primary care
      services. Knowledge of basic mechanisms behind sleep and wakefulness is essential
      for giving adequate information and correct patients' frequent misperception of
      sleep. MATERIAL AND METHODS: The present review is based on literature identified
      through a non-systematic search of Pub-med as well as the authors' own research
      experience. RESULTS: Sleep need (homeostatic factor), circadian rhythm and
      behaviour regulate sleepiness, sleep depth and sleep duration. Falling asleep
      requires central-nervous deactivation. Sleep depth depends on the length of
      wakefulness beforehand, while duration of sleep mainly depends on timing in
      relation to the circadian phase of activation. Activation and wakefulness are the
      combined result of activating several different parts of the brain: thalamus, the
      reticular activation system, basal forebrain, hypothalamus and monoaminergic cell
      groups in the brainstem. Falling asleep is a dynamic process and is primarily a
      consequence of behaviourally induced deactivation. Sleep is especially modulated
      by GABAergic neurons in the thalamus and basal forebrain, but several
      neurotransmitters and endogenous substances modulate sleep and wakefulness. Sleep
      and wakefulness are complex phenomena, and the activity in different brain
      regions is markedly different depending on whether you are awake or asleep.
      Hence, a manipulation of these, e.g. by use of certain medications, may cause
      sleep problems. INTERPRETATION: Knowledge of sleep is essential for adequate
      evaluation and treatment of sleep disturbances.

PMID- 19756060
TI  - [Sleep-related breathing disorders].
AB  - BACKGROUND: Sleep-related breathing disorders (SRBD) is a term that includes
      several different diagnoses. This paper describes aetiology, diagnostics,
      treatment options and consequences of untreated disease, in children and adults.
      MATERIAL AND METHOD: The paper is based on own clinical experience and literature
      identified through a non-systematic search of PubMed and various books. RESULTS:
      The prevalence of SRDB in children and adults is about 10-15% and that for the
      most serious type, OSAS (Obstructive Sleep Apnoea Syndrome), is about 2-4%. A
      sleep study is required to confirm the diagnosis. The clinical symptoms of SRBD
      in adults are heavy snoring, observed apnoeas, gasping for air leading to
      frequent arousals, disturbed sleep and daytime sleepiness. Children are often
      hyperactive and have learning and behaviour difficulties. Untreated patients have
      increased mortality and morbidity. The primary treatment option for patients with
      medium to serious breathing disorders is continuous positive-pressure
      ventilation. Other treatment options are oral devices and surgery. In children,
      surgery (adenotonsilectomy) is the treatment of choice. INTERPRETATION: OSAS is
      the most severe diagnosis among SRBD. Both adults and children show reduced
      cognitive function and quality of life. Various treatment options are available.

PMID- 19756061
TI  - [Insomnia].
AB  - BACKGROUND: Insomnia is the most prevalent sleep disorder. Chronic insomnia
      affects about 10% of the adult population. MATERIAL AND METHOD: This review is
      based on the authors' experience, as well as articles identified through non
      systematic searches in Pubmed. RESULTS: Insomnia is characterized by problems
      with falling asleep, difficulty maintaining sleep, waking up to early and/or poor
      sleep quality. The diagnosis implies that the problem causes some type of daytime
      impairment. Insomnia is divided into several different subtypes. Recent studies
      indicate that insomnia is an independent risk factor for sick leave and
      disability pension. Non-pharmacological treatment, i.e. stimulus control and
      sleep restriction yields better outcome than hypnotics, particularly on a long
      term basis. INTERPRETATION: Insomnia is highly prevalent, and non-pharmacological
      therapy is the best documented treatment.

PMID- 19756062
TI  - [New EU law--an improvement for Norwegian children?].

PMID- 19756063
TI  - [New rescue helicopters--for whom?].

PMID- 19756065
TI  - [Hemochromatosis].

PMID- 19756066
TI  - [Is self-reporting of substance abuse reliable?].

PMID- 19756068
TI  - [Targeted intervention reduces the Cesarean section rate].

PMID- 19756069
TI  - [Bureaucracy or knowledge-based practice?].

PMID- 19756071
TI  - [Taxi driver--film portrait of the insomniac].
AB  - Martin Scorsese's film "Taxi Driver" from 1976 is a cinematic masterpiece. The
      main character cannot sleep. His condition is caused by inner restlessness and
      external commotion. The film shows us New York City's brutal nightlife through
      the distorted mind of a taxi driver.

PMID- 19756072
TI  - [Nine out of ten traffic accidents occur in middle and low income countries].

PMID- 19756073
TI  - [The highest maternal mortality in the world].

PMID- 19756076
TI  - Nonlinearity-induced broadening of resonances in dynamically modulated couplers.
AB  - We report the observation of nonlinearity-induced broadening of resonances in
      dynamically modulated directional couplers. When the refractive index of the
      guiding channels in the coupler is harmonically modulated along the propagation
      direction and is out-of-phase in two channels, coupling can be completely
      inhibited at resonant modulation frequencies. We observe that nonlinearity
      broadens such resonances and that localization can be achieved even in detuned
      systems at power levels well below those required in unmodulated couplers.

PMID- 19756077
TI  - Top-emitting white organic light-emitting devices with a one-dimensional metallic
      dielectric photonic crystal anode.
AB  - Top-emitting white organic light-emitting devices (TEWOLEDs) with 1D metallic
      dielectric photonic crystal (1D MDPC) as an anode are investigated. A quasi
      periodic 1D MDPC anode allowed for fabrication of multiple-peak TEWOLEDs. A two
      peak or three-peak TEWOLED was obtained by simply adjusting the thickness of the
      dielectric layers in the MDPC. The efficiency of the TEWOLEDs are comparable to
      the corresponding bottom WOLED (11.1 cd/A), which are 9.9 (two-peak device) and
      9.4 cd/A (three-peak device), respectively, and the contrast of the TEWOLEDs is
      about twice as high as the bottom device owing to the low reflection of the
      anode.

PMID- 19756078
TI  - Polarization-entangled Bell states generation based on birefringence in high
      nonlinear microstructure fiber at 1.5 microm.
AB  - Polarization-entangled photon pair generation based on two scalar scattering
      processes of the vector four- photon scattering has been demonstrated
      experimentally in high nonlinear microstructure fiber with birefringence. By
      controlling pump polarization state, polarization-entangled Bell states can be
      realized. It provides a simple way to realize efficient and compact fiber-based
      polarization-entangled photon pair sources.

PMID- 19756079
TI  - Doubly active Q switching and mode locking of an all-fiber laser.
AB  - Simultaneous and independent active Q switching and active mode locking of an
      erbium-doped fiber laser is demonstrated using all-fiber modulation techniques. A
      magnetostrictive rod attached to the output fiber Bragg grating modulates the Q
      factor of the Fabry-Perot cavity, whereas active mode locking is achieved by
      amplitude modulation with a Bragg-grating-based acousto-optic device. Fully
      modulated Q-switched mode-locked trains of optical pulses were obtained for a
      wide range of pump powers and repetition rates. For a Q-switched repetition rate
      of 500 Hz and a pump power of 100 mW, the laser generates trains of 12-14 mode
      locked pulses of about 1 ns each, within an envelope of 550 ns, an overall energy
      of 0.65 microJ, and a peak power higher than 250 W for the central pulses of the
      train.

PMID- 19756080
TI  - Iodine-filter-based high spectral resolution lidar for atmospheric temperature
      measurements.
AB  - This paper presents a method for measuring atmosphere temperature profile using a
      single iodine filter as frequency discriminator. This high spectral resolution
      lidar (HSRL) is a system reconfigured with the transmitter of a mobile Doppler
      wind lidar and with a receiving subsystem redesigned to pass the backscattering
      optical signal through the iodine cell twice to filter out the aerosol scattering
      signal and to allow analysis of the molecular scattering spectrum, thus measuring
      temperatures. We report what are believed to be the first results of vertical
      temperature profiling from the ground to 16 km altitude by this lidar system
      (power-aperture product=0.35 Wm(2)). Concurrent observations of an L band
      radiosonde were carried out on June 14 and August 3, 2008, in good agreement with
      HSRL temperature profiles.

PMID- 19756081
TI  - Tilted-pulse time-resolved off-axis digital holography.
AB  - In this Letter we present an improvement of time-resolved off-axis digital
      holography by the use of tilted femtosecond laser pulses. The pulse front tilting
      of the reference beam with respect to the phase front allows larger crossing
      angles to be used for recording of digital holograms without significant
      reduction of pulse interference area (typically limited by low temporal coherence
      of ultrashort pulses). Such approach increases the area of interference fringes,
      thus enabling the higher resolution of the reconstructed image as well as better
      separation of dc term. Temporal resolution is not deteriorated by this method, as
      only the reference pulse is tilted. The proposed technique was applied for direct
      intensity clamping observations of light filaments in water using the laser
      pulses of 30 fs duration.

PMID- 19756082
TI  - Monocrystalline Yb(3+):(Gd,Lu)(2)O(3) channel waveguide laser at 976.8 nm.
AB  - We report on a Yb(3+)-doped sesquioxide waveguide laser based on a lattice
      matched Yb(3+)(3%):(Gd,Lu)(2)O(3) film that has been epitaxially grown on
      Y(2)O(3) using pulsed laser deposition. Rib-channel waveguides have been
      structured by reactive ion etching. Laser emission at 976.8 nm was observed under
      pumping with a Ti(3+):Al(2)O(3) laser at 905 nm. A laser threshold of 17 mW and a
      slope efficiency of 6.7% have been achieved with respect to input power. For an
      incident pump power of 200 mW, a maximum output power of 12 mW could be realized.

PMID- 19756083
TI  - Fano resonances in waveguide arrays with saturable nonlinearity.
AB  - We study a waveguide array with an embedded nonlinear saturable impurity. We
      solve the impurity problem in closed form and find the nonlinear localized modes.
      Next, we consider the scattering of a small-amplitude plane wave by a nonlinear
      impurity mode, and discover regions in parameter space where transmission is
      fully suppressed. We relate these findings with Fano resonances and propose this
      setup as a means to control the transport of light across the array.

PMID- 19756084
TI  - Tapered fibers embedded in silica aerogel.
AB  - We have embedded thin tapered fibers (with diameters down to 1 microm) in silica
      aerogel with low loss. The aerogel is rigid but behaves refractively like air,
      protecting the taper without disturbing light propagation along it. This enables
      a new class of fiber devices exploiting volume evanescent interactions with the
      aerogel itself or with dopants or gases in the pores.

PMID- 19756085
TI  - Shearing interferometer based on the birefringent properties of a spatial light
      modulator.
AB  - We present a shearing interferometer that is based on the birefringent properties
      of a phase-only spatial light modulator. The main advantages of this approach are
      the high flexibility, the robustness, and the light efficiency. In contrast to
      already existing methods the suppression of unwanted diffraction orders is not
      required.

PMID- 19756086
TI  - Tunable phase-stabilized infrared optical parametric amplifier for high-order
      harmonic generation.
AB  - We demonstrate what we believe to be a novel tunable IR optical parametric
      amplifier (OPA) with the passively stabilized carrier-envelope phase (CEP), in
      which a hollow fiber is used to improve the output beam quality and to overcome
      the spatial chirp issue. Pumped by an 800 nm pump source, the output pulses are
      tunable from 1.2 to 2.4 microm with the CEP stabilization. The maximum output
      average energy can reach approximately (1.2 W/40 fs)/1 kHz with the total of (6.8
      W/40 fs)/1 kHz pump energy. Further, the high-order harmonic generation driven by
      the tunable phase-stabilized OPA has been demonstrated.

PMID- 19756087
TI  - Compact optical curvature sensor with a flexible microdisk laser on a polymer
      substrate.
AB  - We demonstrate a chip-scale compact optical curvature sensor. It consists of a
      low threshold InGaAsP microdisk laser on a flexible polydimethylsiloxane polymer
      substrate. The curvature dependence of lasing wavelength was characterized by
      bending the cavity at different bending radii. The measurements showed that the
      lasing wavelength decreases monotonously with an increasing bending curvature. A
      good agreement between experiment and three-dimensional finite-difference time
      domain simulation was also obtained. The sensitivity of the compact device to the
      bending curvature is -23.7 nm/mm from the experiment.

PMID- 19756088
TI  - Optical realization of coherent vibrational dynamics in molecules.
AB  - Optical analogs of coherent vibrational phenomena in molecules, such as light
      induced molecular stabilization and wave packet dynamics at a potential crossing,
      are proposed for light beams in coupled slab waveguides.

PMID- 19756089
TI  - Instant single-photon Fock state tomography.
AB  - Heralded single photons are prepared at a rate of approximately 100 kHz via
      conditional measurements on polarization-nondegenerate biphotons produced in a
      periodically poled potassium-titanyl phosphate crystal. The single-photon Fock
      state is characterized using high-frequency pulsed optical homodyne tomography
      with a fidelity of (57.6+/-0.1)%. The state preparation and detection rates
      allowed us to perform on-the-fly alignment of the apparatus based on real-time
      analysis of the quadrature measurement statistics.

PMID- 19756090
TI  - Single-shot real-time frequency chirp characterization of telecommunication
      optical signals based on balanced temporal optical differentiation.
AB  - A simple single-shot frequency chirp characterization technique for
      telecommunication optical waveforms is introduced. The proposed technique is
      based on what we believe to be a novel balanced all-optical ultrafast
      differentiation scheme, and it enables a real-time conversion of the
      instantaneous frequency variation of an arbitrary complex (amplitude and phase)
      optical signal into a temporal intensity profile while simultaneously providing
      an efficient cancellation of the intensity noise. Single-shot real-time frequency
      chirp measurements of gigahertz-bandwidth phase-only and amplitude and phase
      temporal modulation waveforms are performed.

PMID- 19756091
TI  - Mask-free hybrid long-period fiber grating fabrication by self-assembled periodic
      polymerization in silica hollow optical fiber.
AB  - We report a type of hybrid optical fiber created by filling the central hole of a
      silica hollow optical fiber (HOF) with an organic polymer to serve as the core.
      After suitable curing of the polymer filling of the HOF, a self-assembled one
      dimensional polymer-air periodic structure was created without the need for an
      amplitude mask. This acts as a long-period fiber grating device with an axial
      refractive index modulation. Details of the fabrication method for the hybrid
      fiber grating and its transmission spectra analysis are reported.

PMID- 19756092
TI  - Fast-framing ballistic imaging of velocity in an aerated spray.
AB  - We describe further development of ballistic imaging adapted for the liquid core
      of an atomizing spray. To fully understand spray breakup dynamics, one must
      measure the velocity and acceleration vectors that describe the forces active in
      primary breakup. This information is inaccessible to most optical diagnostics, as
      the signal is occluded by strong scattering in the medium. Ballistic imaging
      mitigates this scattering noise, resolving clean shadowgram-type images of
      structures within the dense spray region. We demonstrate that velocity data can
      be extracted from ballistic images of a spray relevant to fuel-injection
      applications, by implementing a simple, targeted correlation method for
      determining velocity from pairs of spray images. This work presents the first
      ballistic images of a liquid-fuel injector for scramjet combustion, and the first
      velocity information from ballistic images relevant to breakup in the near-field
      of a spray.

PMID- 19756093
TI  - Observation of nonlinear surface waves in modulated waveguide arrays.
AB  - We describe theoretically and study experimentally nonlinear surface waves at the
      edge of a modulated waveguide array with a surface defect and a self-defocusing
      nonlinearity. We fabricate such structures in a LiNbO(3) crystal and demonstrate
      the beam switching to different output waveguides with a change of the light
      intensity due to nonlinear coupling between the linear surface modes supported by
      the array.

PMID- 19756094
TI  - Experimental observation of chaotic phase synchronization of a periodically
      modulated frequency-doubled Nd:YAG laser.
AB  - We present experimental observations of chaotic phase synchronization of a
      sinusoidally modulated frequency-doubled Nd:YAG laser. Periodic and chaotic phase
      synchronization is detected using recurrence analysis and pseudo ensemble
      averaging applied to the observed intensity fluctuations and the modulated pump
      current.

PMID- 19756095
TI  - Optically fed microwave true-time delay based on a compact liquid-crystal
      photonic-bandgap-fiber device.
AB  - An electrically tunable liquid-crystal, photonic-bandgap-fiber-device-based,
      optically fed microwave, true-time delay is demonstrated with the response time
      in the millisecond range. A maximum electrically controlled phase shift of around
      70 degrees at 15 GHz and an averaged 12.9 ps true-time delay over the entire
      modulation frequency range of 1-15 GHz are obtained.

PMID- 19756096
TI  - Highly efficient crossing structure for silicon-on-insulator waveguides.
AB  - A compact waveguide crossing structure with low transmission losses and
      negligible crosstalk is demonstrated for silicon-on-insulator circuits. The
      crossing structure is based on a mode expander optimized by means of a genetic
      algorithm leading to transmission losses lower than 0.2 dB and crosstalk and
      reflection losses below 40 dB in a broad bandwidth of 20 nm. Furthermore, the
      resulting crossing structure has a footprint of only 6x6 microm(2) and does not
      require any additional fabrication steps.

PMID- 19756097
TI  - Yellow-light generation of 5.7 W by intracavity doubling self-Raman laser of
      YVO(4)/Nd:YVO(4) composite.
AB  - A high-power 588 nm light produced by an intracavity frequency-doubling acousto
      optic Q-switched self-frequency Raman laser is reported. A 20-mm-long
      YVO(4)/Nd:YVO(4) composite crystal and a 15-mm-long LiB(3)O(5) (LBO) with
      noncritical phase-matching (theta=90 degrees , phi=0 degrees ) cut were adopted
      for efficient self-Raman laser operation and second-harmonic generation,
      respectively. By the optimizing the focus position of incident pump light and Q
      switch repetition rate, yellow light with 5.7 W average power was generated under
      the pump power of 23.5 W, corresponding to the overall diode-yellow conversion
      efficiency of 24.2% and slope efficiency of 32%. The pulse width is about 16 ns,
      and the pulse energy is up to 95 microJ.

PMID- 19756098
TI  - Experimental demonstration of an all-optical fiber-based Fredkin gate.
AB  - We propose and report on what we believe to be the first experimental
      demonstration of an all-optical fiber-based Fredkin gate for reversible digital
      logic. The simple 3-input/3-output fiber-based nonlinear optical loop mirror
      architecture requires only minor alignment for full operation. A short nonlinear
      element, heavily doped GeO(2) fiber (HDF), allows for a more compact design than
      typical nonlinear fiber gates. The HDF is ideal for studying reversibility,
      functioning as a noise-limited medium, as compared to the semiconductor optical
      amplifier, while allowing for cross-phase modulation, a nondissipative optical
      interaction. We suggest applications for secure communications, based on "cool"
      computing.

PMID- 19756099
TI  - Z-scan technique for investigation of the noninstantaneous optical Kerr
      nonlinearity.
AB  - By treating laser-induced optical Kerr nonlinearity as a noninstantaneous
      decaying process, we present the pulse-duration-dependent Z-scan analytical
      expressions for an arbitrary aperture and an arbitrary nonlinear magnitude. This
      theory has the capacity to characterize the third-order nonlinear refraction
      induced by a laser pulse with its temporal duration being much longer than or
      comparable to the recovery time of the nonlinear effect. Through Z-scan
      measurements at different pulse durations, the nonlinear refractive coefficient
      and the recovery time could be determined unambiguously and simultaneously.
      Furthermore, the theory can be utilized to confirm whether the measured optical
      Kerr nonlinearity is instantaneous or noninstantaneous with respect to the given
      pulse duration.

PMID- 19756100
TI  - Three-dimensional imaging of Forster resonance energy transfer in heterogeneous
      turbid media by tomographic fluorescent lifetime imaging.
AB  - We report a three-dimensional time-resolved tomographic imaging technique for
      localizing protein-protein interaction and protein conformational changes in
      turbid media based on Forster resonant energy-transfer read out using
      fluorescence lifetime. This application of "tomoFRET" employs an inverse
      scattering algorithm utilizing the diffusion approximation to the radiative
      transfer equation applied to a large tomographic data set of time-gated images.
      The approach is demonstrated by imaging a highly scattering cylindrical phantom
      within which are two thin wells containing cytosol preparations of HEK293 cells
      expressing TN-L15, a cytosolic genetically encoded calcium Forster resonant
      energy-transfer sensor. A 10 mM calcium chloride solution was added to one of the
      wells, inducing a protein conformation change upon binding to TN-L15, resulting
      in Forster resonant energy transfer and a corresponding decrease in the donor
      fluorescence lifetime. We successfully reconstruct spatially resolved maps of the
      resulting fluorescence lifetime distribution as well as of the quantum
      efficiency, absorption, and scattering coefficients.

PMID- 19756101
TI  - Experimental observation of pulse trains' destructive interference with a
      femtosecond optical frequency-comb-based interferometer.
AB  - A recently reported interferometric technique using a femtosecond optical
      frequency comb is modified to observe the destructive interference between two
      pairs of pulse trains with different relative delays. Experimental observation of
      the destructive interference shows that the present technique may offer a
      significantly different possibility to reduce the unnecessary reflections. This
      technique can be applied not only to surface profilometry and tomography but also
      to optical superresolution metrology.

PMID- 19756102
TI  - Accurate finite-difference time-domain simulation of anisotropic media by
      subpixel smoothing.
AB  - Finite-difference time-domain methods suffer from reduced accuracy when
      discretizing discontinuous materials. We previously showed that accuracy can be
      significantly improved by using subpixel smoothing of the isotropic dielectric
      function, but only if the smoothing scheme is properly designed. Using recent
      developments in perturbation theory that were applied to spectral methods, we
      extend this idea to anisotropic media and demonstrate that the generalized
      smoothing consistently reduces the errors and even attains second-order
      convergence with resolution.

PMID- 19756103
TI  - Ultraviolet and violet upconversion fluorescence of europium (III) doped in YF(3)
      nanocrystals.
AB  - Under 980 nm excitation, Eu(3+)/Tm(3+)/Yb(3+) tri-doped YF(3) nanocrystals
      emitted ultraviolet and visible fluorescence. Besides the upconversion emissions
      from Tm(3+) ions, not only were the unusual (5)D(2)-->(7)F(3), (5)D(3)-->(7)F(J)
      emissions of Eu(3+) observed, but also the ultraviolet upconversion luminescence
      of Eu(3+) from (5)H(3-7), (5)G(2-6), (5)L(6)-->(7)F(0) transitions were recorded.
      This unique optical property was attributed to the bridging function of Tm(3+)
      ions in populating high-energy states of Eu(3+) ions.

PMID- 19756104
TI  - Coherent control of ultrafast shift currents in GaAs with chirped optical pulses.
AB  - We demonstrate the coherent control of ultrafast shift currents in GaAs with two
      orthogonally polarized linearly chirped laser pulses. By varying the chirp and
      phase delay between the pulses, we achieve the control of the shape of the shift
      current transients in a wide range from a monopolar shape to different bipolar
      shapes (alternating currents). Moreover, the terahertz emission patterns
      resulting from the ultrafast shift currents allow one to determine the sign of
      the chirp of the laser pulses.

PMID- 19756105
TI  - Controlling depth of focus in 3D image reconstructions by flexible and adaptive
      deformation of digital holograms.
AB  - We show here that through an adaptive deformation of digital holograms it is
      possible to manage the depth of focus in 3D imaging reconstruction. Deformation
      is applied to the original hologram with the aim to put simultaneously in focus,
      and in one reconstructed image plane, different objects lying at different
      distances from the hologram plane (i.e., CCD sensor). In the same way, by
      adapting the deformation it is possible to extend the depth of field having a
      tilted object entirely in focus. We demonstrate the method in both lensless as
      well as in microscope configuration.

PMID- 19756106
TI  - Reformulation of the eigenvalue problem in the Fourier modal method with spatial
      adaptive resolution.
AB  - The Fourier modal method equipped with the concept of adaptive spatial resolution
      (FMMASR) is shown to be naturally more stable than the classical Fourier modal
      method toward spurious modes that appear with metallic structures. It is
      demonstrated that this stability can be further improved by reformulating the
      eigenvalue problem of the FMMASR.

PMID- 19756107
TI  - Liquid tunable diffractive/refractive hybrid lens.
AB  - We present a liquid tunable diffractive/refractive hybrid lens fabricated through
      what we believe to be a novel process that combines single-point diamond turning
      with soft lithography techniques. The hybrid lens achieves focal length
      tunability by changing its shape and, at the same time, utilizes the unique
      dispersion property of diffractive surfaces to enhance its spectral performance
      within a wide tuning range.

PMID- 19756108
TI  - Optically controlled loss in an optical fiber.
AB  - The use of upconversion to attenuate/modulate optical signals is proposed, and
      experimental results are presented. In this light controlling light approach, a
      711.2 nm, 700 mW beam propagating in a Tm(3+)-doped fluorozirconate optical fiber
      was attenuated down to 150 mW by copropagating a 1117 nm beam. Further
      characterizations concerning time response of the transmittance revealed the
      limits and potential of the scheme. The maximum attenuation of a 45 cm fiber,
      75%, was reached up to 400 Hz, and at least 37% modulation was measured at 770
      Hz. Potential applications include Q switching of lasers and in-fiber light
      controllable optical attenuation.

PMID- 19756109
TI  - Broadly tunable carrier envelope phase stable optical parametric amplifier pumped
      by a monolithic ytterbium fiber amplifier.
AB  - In an effort to develop a robust and efficient front end for a chirped-pulse
      parametric amplification chain, we demonstrate a broadband difference-frequency
      converter driven by a monolithic femtosecond Yb-doped-fiber amplifier and
      emitting carrier-envelope-offset-free pulses with the energy of tens of
      nanojoules tunable in the wavelength range from 1200 nm to beyond 2 mum. Next to
      providing these seed pulses, the system enables direct optical synchronization of
      Nd- and Yb-doped pump lasers for subsequent parametric amplification.

PMID- 19756110
TI  - Low-threshold thin-film III-V lasers bonded to silicon with front and back side
      defined features.
AB  - A III-V thin-film single-quantum-well edge-emitting laser is patterned on both
      sides of the epitaxial layer and bonded to silicon. Injected threshold current
      densities of 420 A/cm(2) for gain-guided lasers with bottom p-stripes and top n
      stripes and 244 A/cm(2) for index-guided bottom p-ridge and top n-stripe lasers
      are measured with a lasing wavelength of approximately 995 nm. These threshold
      current densities, among the lowest for thin-film edge-emitting lasers on silicon
      reported to date (to our knowledge), enable the implementation of integrated
      applications such as power-efficient portable chip-scale photonic sensing
      systems.

PMID- 19756111
TI  - Low-contrast bandgaps of a planar parabolic spiral lattice.
AB  - We show that a planar aperiodic lattice, mimicking the appearance of a sunflower,
      supports photonic bandgaps for weak dielectric contrast. The pattern's high
      orientational order and spatially uniform modal pitch yields an isotropic Fourier
      space. A 2D structure of cylinders (=2) in air possesses a wide 21% TM bandgap,
      versus 5.6% for a sixfold lattice or 14% for a 12-fold fractal tiling. The
      isotropic gap frequencies imply flat bands, and thus application in nonlinear
      optics and low threshold lasers, where a reduced group velocity in all directions
      may be desired.

PMID- 19756112
TI  - Observation of interference in a fiber taper interferometer with a subwavelength
      tip and its sensing applications.
AB  - We present an ultraminiature fiber-optic sensor based on a fiber taper
      interferometer with a subwavelength tip. The interferometer is fabricated on the
      end face of a single-mode fiber by wet etching using buffered hydrofluoric acid.
      The process creates a protruding core on the end face with a tapered shape.
      Strong interference is observed between the reflections from the fiber cladding
      and the tip of the taper even for tip size as small as lambda/4. A time-domain
      analysis of the sensor spectrum recorded during the etching process produces the
      temporal evolution of both reflections, indicating that the interference
      mechanism involves intermodal coupling. The interferometer's sensing application
      is demonstrated by the effective measurement of refractive index and temperature.

PMID- 19756113
TI  - Highly efficient diamond Raman laser.
AB  - We report an efficient 532 nm pumped external cavity diamond Raman laser
      generating output chiefly at the 573 nm first Stokes. At a pulse repetition rate
      of 5 kHz, the Raman laser generated 1.2 W output with a conversion efficiency of
      63.5%, a slope efficiency of 75%, a pulse peak instantaneous conversion
      efficiency of 85%, and a peak photon conversion efficiency of 91%. The laser
      generated a maximum output energy of 0.67 mJ by increasing the pump beam size and
      the pulse energy. The efficiency is commensurate with the highest previously
      reported for other Raman materials pumped by Q-switched lasers.

PMID- 19756114
TI  - High-power wavelength-swept laser in Littman telescope-less polygon filter and
      dual-amplifier configuration for multichannel optical coherence tomography.
AB  - We report a high-power wavelength-swept laser source for multichannel optical
      coherence tomography (OCT) imaging. Wavelength tuning is performed by a compact
      telescope-less polygon-based filter in Littman arrangement. High output power is
      achieved by incorporating two serial semiconductor optical amplifiers in the
      laser cavity in Fourier domain mode-locked configuration. The measured wavelength
      tuning range of the laser is 111 nm centered at 1329 nm, coherence length of 5.5
      mm, and total average output power of 131 mW at 43 kHz sweeping rate.
      Multichannel simultaneous OCT imaging at an equivalent A-scan rate of 258 kHz is
      demonstrated.

PMID- 19756115
TI  - Large third-order susceptibility and third-harmonic generation in centrosymmetric
      Cu(2)O crystal.
AB  - We present what we believe to be the first experimental determination of the
      third-order optical susceptibility chi((3)) of bulk cuprous oxide (Cu(2)O)
      crystals. The measured nonlinear refractive index, obtained with the Z-scan
      technique at 1064 nm, is n(2)=1.32x10(-10) esu, while the two-photon absorption
      coefficient is beta=5.0 cm/GW of Cu(2)O. We also observe strong third-harmonic
      generation (THG) from Cu(2)O in our detection range owing to its unique crystal
      and electronic structure. Considering that the first nonvanishing nonlinear term
      is chi((3)), this classical semiconductor could be utilized as a promising active
      THG medium.

PMID- 19756116
TI  - Laser direct writing of nanoreliefs in Sn nanofilms.
AB  - High-resolution (approximately 200 nm) nanoreliefs, which possess a controllable
      height change (Deltah, up to film thickness) and transmittance or reflectance,
      have been successfully fabricated in 12-nm-thick Sn films by using 532 nm pulsed
      laser direct writing. Different from current micro/nanofabrication techniques,
      the height change of the nanoreliefs is generated by a laser-induced-thickening
      process. The majority of the height change comes from a balling and coarsening
      effect rather than oxidation of grains. Because both optical density and Deltah
      of the nanoreliefs are almost linear to laser power, the optical images can
      highly resemble the topographic images. This technique is useful for fabricating
      complicated nanorelief structures and fine images.

PMID- 19756117
TI  - Femtosecond Yb:Lu(2)O(3) thin disk laser with 63 W of average power.
AB  - We present successful power-scaling of an Yb:Lu(2)O(3) thin disk laser to record
      high-power levels both in cw and mode-locked operation. In a simple multimode
      resonator we achieved 149 W of output power in cw operation with 73% optical-to
      optical efficiency (eta(opt)). Building an 81 MHz fundamental transverse mode
      resonator with dispersion compensation and a semiconductor saturable absorber
      mirror (SESAM) for passive mode locking we achieved 63 W of average power in 535
      fs pulses (eta(opt)=35%). The output beam is nearly diffraction limited
      (M(2)<1.2). The 0.78 microJ pulses with a peak power of 1.28 MW had a central
      wavelength of 1034 nm and were close to the Fourier transform limit. With an
      SESAM with a larger modulation depth we obtained pulses as short as 329 fs at 40
      W average power corresponding to a pulse energy of 0.49 microJ and a peak power
      of 1.32 MW.

PMID- 19756118
TI  - Effects of organic surfactant on fluorescence concentration quenching of Nd(3+)
      doped LaF(3) nanoparticles.
AB  - Distinct effects of organic surfactant [ammonium di-n-octadecyldithioposhate
      (ADDP)] on the fluorescent property of Nd(3+)-doped LaF(3) nanoparticles were
      demonstrated by incorporating different amounts of organic surfactant on the
      nanoparticles. The photoluminescence spectra and fluorescence quenching
      concentrations of the nanoparticles were measured. A high fluorescence quenching
      concentration (of about 23.4 wt.%) for the LnF(2.36)ADDP(0.64) nanoparticles was
      observed. The quenching concentration could be adjusted by varying the amount of
      organic surfactant. This phenomenon is ascribed to the protection of organic
      surfactants coordinated on nanoparticles' fluorescent centers.

PMID- 19756119
TI  - Coupling of stochastic electromagnetic beams into optical fibers.
AB  - We derive a general analytic expression for the coupling efficiency when a
      partially coherent, partially polarized beam is coupled into a multimode optical
      fiber. We adopt the Gaussian-Schell model for incident electromagnetic beams and
      use our general result to discuss the effects of the partial coherence and
      partial polarization on the coupling efficiency of an optical beam focused onto a
      step-index, single-mode fiber with a lens. Our results should be useful for any
      application requiring coupling of partially coherent beams into optical fibers.

PMID- 19756120
TI  - Brillouin cross-gain modulation and 10 m/s group velocity.
AB  - We introduce a method of achieving cross-gain modulation and slow light using the
      Brillouin nonlinearity in an optical fiber. We demonstrate approximatetely 10 m/s
      group velocity using this technique with milliwatts of optical power at room
      temperature.

PMID- 19756121
TI  - 3D tensor factorization approach to single-frame model-free blind-image
      deconvolution.
AB  - By applying a bank of 2D Gabor filters to a blurred image, single-frame blind
      image deconvolution (SF BID) is formulated as a 3D tensor factorization (TF)
      problem, with the key contribution that neither origin nor size of the spatially
      invariant blurring kernel is required to be known or estimated. Mixing matrix,
      the original image, and its spatial derivatives are identified from the factors
      in the Tucker3 model of the multichannel version of the blurred image. Previous
      approaches to 2D Gabor-filter-bank-based SF BID relied on 2D representation of
      the multichannel version of the blurred image and matrix factorization methods
      such as nonnegative matrix factorization (NMF) and independent component analysis
      (ICA). Unlike matrix factorization-based methods 3D TF preserves local structure
      in the image. Moreover, 3D TF based on the PARAFAC model is unique up to
      permutation and scales under very mild conditions. To achieve this, NMF and ICA
      respectively require enforcement of sparseness and statistical independence
      constraints on the original image and its spatial derivatives. These constraints
      are generally not satisfied. The 3D TF-based SF BID method is demonstrated on an
      experimental defocused red-green-blue image.

PMID- 19756122
TI  - Observation of discrete solitons in lattices with second-order interaction.
AB  - We present what we believe to be the first experimental demonstration of discrete
      solitons under the influence of first- and second-order lattice site interaction
      in zigzag femtosecond laser-written waveguide arrays. We show how the formation
      of these entities is affected by different ratios of the interaction strength.
      Increasing the second-order coupling between the lattices sites yields an almost
      linear increase of the input power required for soliton formation.

PMID- 19756123
TI  - Portraying polarization state of terahertz pulse generated by a two-color laser
      field in air.
AB  - By using an electro-optic sampling technique, the instantaneous field vector of
      the terahertz (THz) pulse generated by mixing a near-IR femtosecond pulse and its
      second harmonic in air has been studied. The polarization of the investigated THz
      pulse is found to be predominantly linear and orthogonal to that of the second
      harmonic, revealing the major role of chi((3))(xyxy) during the four-wave mixing
      process.

PMID- 19756124
TI  - Volume electric dipole origin of second-harmonic generation from metallic
      membrane with noncentrosymmetric patterns.
AB  - We analytically study second-harmonic (SH) generation from thin metallic films
      with subwavelength noncentrosymmetric patterns. Because the thickness of the film
      is much smaller than the SH wavelength, retardation effects are negligible. The
      far-field SH intensities are thus dominated by an effective electric dipole. It
      is further demonstrated that internal bulk SH polarization density is comparable
      with its surface counterpart. The electric dipole, consequently, originates from
      the entire volume of the metallic membrane.

PMID- 19756125
TI  - Compact coherent anti-Stokes Raman scattering microscope based on a picosecond
      two-color Er:fiber laser system.
AB  - We present a compact coherent anti-Stokes Raman scattering microscope based on a
      widely tunable picosecond Er:fiber laser. Intense and bandwidth-limited 1 ps pump
      pulses at a center wavelength of 775 nm are generated via frequency mixing within
      the broadband fundamental at 1.55 microm. Narrowband Stokes pulses are obtained
      by frequency shifting of solitons in a highly nonlinear bulk fiber and subsequent
      second-harmonic generation. The tuning range from 850 nm to 1100 nm gives access
      to vibrational resonances between 1150 cm(-1) and 3800 cm(-1). A first imaging
      application in the spectral region of CH stretch vibrations is demonstrated.

PMID- 19756126
TI  - Quantitative characterization of turbid media using pressure contrast acousto
      optic imaging.
AB  - An acousto-optic imaging technique suitable for the local and quantitative
      determination of subsurface optical properties in turbid media is presented.
      Acousto-optic signals elicited by ultrasound pulses at two different peak
      pressures in turbid media are detected by using photorefractive-crystal-based
      interferometry. The ratio of the measured signals, once calibrated for a
      particular set of pressure pulses, is found to give a direct measure of the
      reduced scattering coefficient of the interaction region between the light and
      sound. Measurements of the reduced scattering coefficient of inclusions buried in
      diffuse tissue phantoms are demonstrated.

PMID- 19756127
TI  - Imaging of epithelial tissue in vivo based on excitation of multiple endogenous
      nonlinear optical signals.
AB  - We demonstrate an integrated optical microscope to image the living epithelial
      tissue by simultaneously exciting multiple endogenous nonlinear optical signals.
      By employing the spectral lifetime detection capability, this technology provides
      a unique approach to sensing the fine structure, the protein distribution, and
      the cellular metabolism of epithelial tissue in vivo. In particular, we
      investigated the two-photon excitation fluorescence (TPEF) of tryptophan, an
      essential amino acid serving as the building block of protein. Our findings show
      that the TPEF of cellular tryptophan produces a good contrast to reveal the
      morphology of the epithelial cell layer, and the contrast can be further enhanced
      by applying low-concentration acetic acid.

PMID- 19756128
TI  - Crystal-based device for combining light beams.
AB  - Using a monoprism of anisotropic crystal with special configuration, we can
      combine between two and four laser beams for them to propagate in a single
      direction. This method is simpler than previously used ones.

PMID- 19756129
TI  - Bulk sensing experiments using a surface-plasmon interferometer.
AB  - Experimental evidence supporting the use of a surface-plasmon interferometer as a
      biosensor is presented. The device is shown to be capable of bulk refractive
      index sensing (bulk refractometry) and has a spectral interrogation sensitivity
      of 315.145 nm/refractive index unit.

PMID- 19756130
TI  - Conducting single-transverse-mode operation with a wide tuning range in
      commercial multimode VCSELs by beam-profile-adapted optical feedback.
AB  - This research investigated the feasibility of employing beam-profile-adapted
      optical feedback to conduct commercial multi-transverse-mode vertical-cavity
      surface-emitting lasers (VCSELs) to emit a single transverse mode with a wide
      tuning range. Experimentally, for a VCSEL with its solitary spectrum consisting
      of almost no fundamental transverse mode, the fundamental transverse mode could
      be conducted to lase with a tuning range of about 1285 GHz and side-mode
      suppression ratio of around 20 dB. These results can greatly enhance the
      performance of VCSELs in many applications.

PMID- 19756131
TI  - Amplification of surface plasmon polaritons in the presence of nonlinearity and
      spectral signatures of threshold crossover.
AB  - We describe the effects of nonlinearity on propagation of surface plasmon
      polaritons (SPPs) at an interface between a metal and an amplifying medium of the
      externally pumped two-level atoms. Using Maxwell equations we derive the
      nonlinear dispersion law and demonstrate that the nonlinear saturation of the
      linear gain leads to formation of stationary SPP modes with the intensities
      independent from the propagation distance. Transition to the regime of stationary
      propagation is similar to the threshold crossover in lasers and leads to
      narrowing of the SPP spectrum.

PMID- 19756132
TI  - Plasmonic phenomena in indium tin oxide and ITO-Au hybrid films.
AB  - The observation of surface-plasmon resonances in indium tin oxide (ITO) thin
      films is complemented with the effects of hybrid ITO/Au conducting layers where
      charge densities can be tuned. Where carrier densities are similar (ITO and
      nanoparticle Au), the plasmonic behavior is that of a monolithic ITO thin film.
      Where the carrier density of one layer is much greater than that of the other
      (ITO and Au metal), boundary conditions lead to cancelation of the surface
      plasmon. In the latter case a capacitivelike plasmon resonance is observed for
      sufficiently thin films.

PMID- 19756133
TI  - Frequency dependence of the optical force between two coupled waveguides.
AB  - We investigate the frequency dependence of the optical force between two coupled
      waveguides using the supermode theory. We show that the frequency dependence of
      the optical force in a coupled waveguide system is determined by the dispersion
      relations of uncoupled individual waveguides. We further numerically calculate
      the optical force of three representative coupled systems at different
      frequencies and show that these results agree well with the supermode analysis.

PMID- 19756134
TI  - Fiber-assisted single-photon spectrograph.
AB  - We demonstrate the implementation of a fiber-integrated spectrograph utilizing
      chromatic group velocity dispersion (GVD) in a single-mode fiber. By means of GVD
      we stretch an ultrafast pulse in time in order to spectrally resolve single
      photons in the time domain, detected by single-photon counting modules with very
      accurate temporal resolution. As a result, the spectrum of a very weak pulse is
      recovered from a precise time measurement with high signal-to-noise ratio. We
      demonstrate the potential of our technique by applying our scheme to analyzing
      the joint spectral intensity distribution of a parametric downconversion source
      at a telecommunication wavelength.

PMID- 19756135
TI  - Very-large-mode-area, single-mode multicore fiber.
AB  - A single-mode evanescently coupled multicore fiber consisting of 19 hexagonally
      arranged cores is investigated. Theoretical and experimental results are
      presented and compared to an equivalent hypothetical step-index fiber. A
      fundamental mode with an effective area of 465 microm(2) and a beam propagation
      factor M(2) of 1.02 was measured, showing the high potential of the developed
      fiber.

PMID- 19756136
TI  - Mode-locked Yb-doped Bragg fiber laser.
AB  - We report on a mode-locked fiber laser featuring an Yb-doped large-mode-area
      Bragg fiber and exploiting dissipative-soliton pulse shaping. Reliable self
      starting mode-locking is achieved using a fast semiconductor saturable absorber
      mirror. The laser generates 30 nJ chirped pulses at 17 MHz repetition rate for an
      average power of 510 mW. The 3.2 ps output pulses are compressed outside the
      cavity to 440 fs.

PMID- 19756137
TI  - A Point Process Approach to Assess Dynamic Baroreflex Gain.
AB  - Evaluation of arterial baroreflex in cardiovascular control is an important topic
      in cardiology and clinical medicine. In this paper, we present a point process
      approach to estimate the dynamic baroreflex gain in a closed-loop model of the
      cardiovascular system. Specifically, the inverse Gaussian probability
      distribution is used to model the heartbeat interval, whereas the instantaneous
      mean is modulated by a bivariate autoregressive model that contains the previous
      R-R intervals and systolic blood pressure (SBP) measures. The instantaneous
      baroreflex gain is estimated in the feedback loop with a point process filter,
      while the RR->SBP feedforward frequency response gain can be estimated by a
      Kalman filter. The proposed estimation approach provides a quantitative
      assessment of interacting heartbeat dynamics and hemodynamics. We validate our
      approach with real physiological signals and evaluate the proposed model with
      established goodness-of-fit tests.

PMID- 19756138
TI  - EpiCollect: linking smartphones to web applications for epidemiology, ecology and
      community data collection.
AB  - BACKGROUND: Epidemiologists and ecologists often collect data in the field and,
      on returning to their laboratory, enter their data into a database for further
      analysis. The recent introduction of mobile phones that utilise the open source
      Android operating system, and which include (among other features) both GPS and
      Google Maps, provide new opportunities for developing mobile phone applications,
      which in conjunction with web applications, allow two-way communication between
      field workers and their project databases. METHODOLOGY: Here we describe a
      generic framework, consisting of mobile phone software, EpiCollect, and a web
      application located within www.spatialepidemiology.net. Data collected by
      multiple field workers can be submitted by phone, together with GPS data, to a
      common web database and can be displayed and analysed, along with previously
      collected data, using Google Maps (or Google Earth). Similarly, data from the web
      database can be requested and displayed on the mobile phone, again using Google
      Maps. Data filtering options allow the display of data submitted by the
      individual field workers or, for example, those data within certain values of a
      measured variable or a time period. CONCLUSIONS: Data collection frameworks
      utilising mobile phones with data submission to and from central databases are
      widely applicable and can give a field worker similar display and analysis tools
      on their mobile phone that they would have if viewing the data in their
      laboratory via the web. We demonstrate their utility for epidemiological data
      collection and display, and briefly discuss their application in ecological and
      community data collection. Furthermore, such frameworks offer great potential for
      recruiting 'citizen scientists' to contribute data easily to central databases
      through their mobile phone.

PMID- 19756139
TI  - A new basal sauropod dinosaur from the middle Jurassic of Niger and the early
      evolution of sauropoda.
AB  - BACKGROUND: The early evolution of sauropod dinosaurs is poorly understood
      because of a highly incomplete fossil record. New discoveries of Early and Middle
      Jurassic sauropods have a great potential to lead to a better understanding of
      early sauropod evolution and to reevaluate the patterns of sauropod
      diversification. PRINCIPAL FINDINGS: A new sauropod from the Middle Jurassic of
      Niger, Spinophorosaurus nigerensis n. gen. et sp., is the most complete basal
      sauropod currently known. The taxon shares many anatomical characters with Middle
      Jurassic East Asian sauropods, while it is strongly dissimilar to Lower and
      Middle Jurassic South American and Indian forms. A possible explanation for this
      pattern is a separation of Laurasian and South Gondwanan Middle Jurassic sauropod
      faunas by geographic barriers. Integration of phylogenetic analyses and
      paleogeographic data reveals congruence between early sauropod evolution and
      hypotheses about Jurassic paleoclimate and phytogeography. CONCLUSIONS:
      Spinophorosaurus demonstrates that many putatively derived characters of Middle
      Jurassic East Asian sauropods are plesiomorphic for eusauropods, while South
      Gondwanan eusauropods may represent a specialized line. The anatomy of
      Spinophorosaurus indicates that key innovations in Jurassic sauropod evolution
      might have taken place in North Africa, an area close to the equator with summer
      wet climate at that time. Jurassic climatic zones and phytogeography possibly
      controlled early sauropod diversification.

PMID- 19756140
TI  - Identifying and characterizing a novel protein kinase STK35L1 and deciphering its
      orthologs and close-homologs in vertebrates.
AB  - BACKGROUND: The human kinome containing 478 eukaryotic protein kinases has over
      100 uncharacterized kinases with unknown substrates and biological functions. The
      Ser/Thr kinase 35 (STK35, Clik1) is a member of the NKF 4 (New Kinase Family 4)
      in the kinome with unknown substrates and biological functions. Various high
      throughput studies indicate that STK35 could be involved in various human
      diseases such as colorectal cancer and malaria. METHODOLOGY/PRINCIPAL FINDINGS:
      In this study, we found that the previously published coding sequence of the
      STK35 gene is incomplete. The newly identified sequence of the STK35 gene codes
      for a protein of 534 amino acids with a N-terminal elongation of 133 amino acids.
      It has been designated as STK35L (STK35 long). Since it is the first of further
      homologous kinases we termed it as STK35L1. The STK35L1 protein (58 kDa on SDS
      PAGE), but not STK35 (44 kDa), was found to be expressed in all human cells
      studied (endothelial cells, HeLa, and HEK cells) and was down-regulated after
      silencing with specific siRNA. EGFP-STK35L1 was localized in the nucleus and the
      nucleolus. By combining syntenic and gene structure pattern data and homology
      searches, two further STK35L1 homologs, STK35L2 (previously known as PDIK1L) and
      STK35L3, were found. All these protein kinase homologs were conserved throughout
      the vertebrates. The STK35L3 gene was specifically lost during placental
      mammalian evolution. Using comparative genomics, we have identified orthologous
      sets of these three protein kinases genes and their possible ancestor gene in two
      sea squirt genomes. CONCLUSIONS/SIGNIFICANCE: We found the full-length coding
      sequence of the STK35 gene and termed it as STK35L1. We identified a new third
      STK35-like gene, STK35L3, in vertebrates and a possible ancestor gene in sea
      squirt genome. This study will provide a comprehensive platform to explore the
      role of STK35L kinases in cell functions and human diseases.

PMID- 19756141
TI  - Transient facial nerve paralysis (Bell's palsy) following intranasal delivery of
      a genetically detoxified mutant of Escherichia coli heat labile toxin.
AB  - BACKGROUND: An association was previously established between facial nerve
      paralysis (Bell's palsy) and intranasal administration of an inactivated
      influenza virosome vaccine containing an enzymatically active Escherichia coli
      Heat Labile Toxin (LT) adjuvant. The individual component(s) responsible for
      paralysis were not identified, and the vaccine was withdrawn.
      METHODOLOGY/PRINCIPAL FINDINGS: Subjects participating in two contemporaneous non
      randomized Phase 1 clinical trials of nasal subunit vaccines against Human
      Immunodeficiency Virus and tuberculosis, both of which employed an enzymatically
      inactive non-toxic mutant LT adjuvant (LTK63), underwent active follow-up for
      adverse events using diary-cards and clinical examination. Two healthy subjects
      experienced transient peripheral facial nerve palsies 44 and 60 days after
      passive nasal instillation of LTK63, possibly a result of retrograde axonal
      transport after neuronal ganglioside binding or an inflammatory immune response,
      but without exaggerated immune responses to LTK63. CONCLUSIONS/SIGNIFICANCE:
      While the unique anatomical predisposition of the facial nerve to compression
      suggests nasal delivery of neuronal-binding LT-derived adjuvants is inadvisable,
      their continued investigation as topical or mucosal adjuvants and antigens
      appears warranted on the basis of longstanding safety via oral, percutaneous, and
      other mucosal routes.

PMID- 19756142
TI  - Biphasic myopathic phenotype of mouse DUX, an ORF within conserved FSHD-related
      repeats.
AB  - Facioscapulohumeral muscular dystrophy (FSHD) is caused by contractions of D4Z4
      repeats at 4q35.2 thought to induce misregulation of nearby genes, one of which,
      DUX4, is actually localized within each repeat. A conserved ORF (mDUX), embedded
      within D4Z4-like repeats, encoding a double-homeodomain protein, was recently
      identified on mouse chromosome 10. We show here that high level mDUX expression
      induces myoblast death, while low non-toxic levels block myogenic differentiation
      by down-regulating MyoD and Myf5. Toxicity and MyoD/Myf5 expression changes were
      competitively reversed by overexpression of Pax3 or Pax7, implying mechanistic
      similarities with the anti-myogenic activity of human DUX4. We tested the effect
      of mDUX expression on Xenopus development, and found that global overexpression
      led to abnormalities in gastrulation. When targeted unilaterally into blastomeres
      fated to become tail muscle in 16-cell embryos, mDUX caused markedly reduced tail
      myogenesis on the injected side. These novel cell and animal models highlight the
      myopathic nature of sequences within the FSHD-related repeat array.

PMID- 19756143
TI  - Role of polypyrimidine tract binding protein in mediating internal initiation of
      translation of interferon regulatory factor 2 RNA.
AB  - BACKGROUND: Earlier we have reported translational control of interferon
      regulatory factor 2 (IRF2) by internal initiation (Dhar et al, Nucleic Acids Res,
      2007). The results implied possible role of IRF2 in controlling the intricate
      balance of cellular gene expression under stress conditions in general. Here we
      have investigated the secondary structure of the Internal Ribosome Entry Site of
      IRF2 RNA and demonstrated the role of PTB protein in ribosome assembly to
      facilitate internal initiation. METHODOLOGY/PRINCIPAL FINDINGS: We have probed
      the putative secondary structure of the IRF2 5'UTR RNA using various enzymatic
      and chemical modification agents to constrain the secondary structure predicted
      from RNA folding algorithm Mfold. The IRES activity was found to be influenced by
      the interaction of trans-acting factor, polypyrimidine tract binding protein
      (PTB). Deletion of 25 nts from the 3'terminus of the 5'untranslated region
      resulted in reduced binding with PTB protein and also showed significant decrease
      in IRES activity compared to the wild type. We have also demonstrated putative
      contact points of PTB on the IRF2-5'UTR using primer extension inhibition assay.
      Majority of the PTB toe-prints were found to be restricted to the 3'end of the
      IRES. Additionally, Circular Dichroism (CD) spectra analysis suggested change in
      the conformation of the RNA upon PTB binding. Further, binding studies using S10
      extract from HeLa cells, partially silenced for PTB gene expression, resulted in
      reduced binding by other trans-acting factors. Finally, we have demonstrated that
      addition of recombinant PTB enhances ribosome assembly on IRF2 IRES suggesting
      possible role of PTB in mediating internal initiation of translation of IRF2 RNA.
      CONCLUSION/SIGNIFICANCE: It appears that PTB binding to multiple sites within
      IRF2 5'UTR leads to a conformational change in the RNA that facilitate binding of
      other trans-acting factors to mediate internal initiation of translation.

PMID- 19756144
TI  - Cytosolic superoxide dismutase (SOD1) is critical for tolerating the oxidative
      stress of zinc deficiency in yeast.
AB  - Zinc deficiency causes oxidative stress in many organisms including the yeast
      Saccharomyces cerevisiae. Previous studies of this yeast indicated that the Tsa1
      peroxiredoxin is required for optimal growth in low zinc because of its role in
      degrading H(2)O(2). In this report, we assessed the importance of other
      antioxidant genes to zinc-limited growth. Our results indicated that the
      cytosolic superoxide dismutase Sod1 is also critical for growth under zinc
      limiting conditions. We also found that Ccs1, the copper-delivering chaperone
      required for Sod1 activity is essential for optimal zinc-limited growth. To our
      knowledge, this is the first demonstration of the important roles these proteins
      play under this condition. It has been proposed previously that a loss of Sod1
      activity due to inefficient metallation is one source of reactive oxygen species
      (ROS) under zinc-limiting conditions. Consistent with this hypothesis, we found
      that both the level and activity of Sod1 is diminished in zinc-deficient cells.
      However, under conditions in which Sod1 was overexpressed in zinc-limited cells
      and activity was restored, we observed no decrease in ROS levels. Thus, these
      data indicate that while Sod1 activity is critical for low zinc growth,
      diminished Sod1 activity is not a major source of the elevated ROS observed under
      these conditions.

PMID- 19756145
TI  - Copper-triggered aggregation of ubiquitin.
AB  - Neurodegenerative disorders share common features comprising aggregation of
      misfolded proteins, failure of the ubiquitin-proteasome system, and increased
      levels of metal ions in the brain. Protein aggregates within affected cells often
      contain ubiquitin, however no report has focused on the aggregation propensity of
      this protein. Recently it was shown that copper, differently from zinc, nickel,
      aluminum, or cadmium, compromises ubiquitin stability and binds to the N-terminus
      with 0.1 micromolar affinity. This paper addresses the role of copper upon
      ubiquitin aggregation. In water, incubation with Cu(II) leads to formation of
      spherical particles that can progress from dimers to larger conglomerates. These
      spherical oligomers are SDS-resistant and are destroyed upon Cu(II) chelation or
      reduction to Cu(I). In water/trifluoroethanol (80:20, v/v), a mimic of the local
      decrease in dielectric constant experienced in proximity to a membrane surface,
      ubiquitin incubation with Cu(II) causes time-dependent changes in circular
      dichroism and Fourier-transform infrared spectra, indicative of increasing beta
      sheet content. Analysis by atomic force and transmission electron microscopy
      reveals, in the given order, formation of spherical particles consistent with the
      size of early oligomers detected by gel electrophoresis, clustering of these
      particles in straight and curved chains, formation of ring structures, growth of
      trigonal branches from the rings, coalescence of the trigonal branched structures
      in a network. Notably, none of these ubiquitin aggregates was positive to tests
      for amyloid and Cu(II) chelation or reduction produced aggregate disassembly. The
      early formed Cu(II)-stabilized spherical oligomers, when reconstituted in 1
      palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) liposomes and in POPC
      planar bilayers, form annular and pore-like structures, respectively, which are
      common to several neurodegenerative disorders including Parkinson's, Alzheimer's,
      amyotrophic lateral sclerosis, and prion diseases, and have been proposed to be
      the primary toxic species. Susceptibility to aggregation of ubiquitin, as it
      emerges from the present study, may represent a potential risk factor for disease
      onset or progression while cells attempt to tag and process toxic substrates.

PMID- 19756146
TI  - Complete genome sequence of Francisella tularensis subspecies holarctica FTNF002
      00.
AB  - Francisella tularensis subspecies holarctica FTNF002-00 strain was originally
      obtained from the first known clinical case of bacteremic F. tularensis pneumonia
      in Southern Europe isolated from an immunocompetent individual. The FTNF002-00
      complete genome contains the RD(23) deletion and represents a type strain for a
      clonal population from the first epidemic tularemia outbreak in Spain between
      1997-1998. Here, we present the complete sequence analysis of the FTNF002-00
      genome. The complete genome sequence of FTNF002-00 revealed several large as well
      as small genomic differences with respect to two other published complete genome
      sequences of F. tularensis subsp. holarctica strains, LVS and OSU18. The FTNF002
      00 genome shares >99.9% sequence similarity with LVS and OSU18, and is also
      approximately 5 MB smaller by comparison. The overall organization of the FTNF002
      00 genome is remarkably identical to those of LVS and OSU18, except for a single
      3.9 kb inversion in FTNF002-00. Twelve regions of difference ranging from 0.1-1.5
      kb and forty-two small insertions and deletions were identified in a comparative
      analysis of FTNF002-00, LVS, and OSU18 genomes. Two small deletions appear to
      inactivate two genes in FTNF002-00 causing them to become pseudogenes; the intact
      genes encode a protein of unknown function and a drug:H(+) antiporter. In
      addition, we identified ninety-nine proteins in FTNF002-00 containing amino acid
      mutations compared to LVS and OSU18. Several non-conserved amino acid
      replacements were identified, one of which occurs in the virulence-associated
      intracellular growth locus subunit D protein. Many of these changes in FTNF002-00
      are likely the consequence of direct selection that increases the fitness of this
      subsp. holarctica clone within its endemic population. Our complete genome
      sequence analyses lay the foundation for experimental testing of these
      possibilities.

PMID- 19756147
TI  - Resolving the role of actoymyosin contractility in cell microrheology.
AB  - Einstein's original description of Brownian motion established a direct
      relationship between thermally-excited random forces and the transport properties
      of a submicron particle in a viscous liquid. Recent work based on reconstituted
      actin filament networks suggests that nonthermal forces driven by the motor
      protein myosin II can induce large non-equilibrium fluctuations that dominate the
      motion of particles in cytoskeletal networks. Here, using high-resolution
      particle tracking, we find that thermal forces, not myosin-induced fluctuating
      forces, drive the motion of submicron particles embedded in the cytoskeleton of
      living cells. These results resolve the roles of myosin II and contractile
      actomyosin structures in the motion of nanoparticles lodged in the cytoplasm,
      reveal the biphasic mechanical architecture of adherent cells-stiff contractile
      stress fibers interdigitating in a network at the cell cortex and a soft actin
      meshwork in the body of the cell, validate the method of particle tracking
      microrheology, and reconcile seemingly disparate atomic force microscopy (AFM)
      and particle-tracking microrheology measurements of living cells.

PMID- 19756148
TI  - Ligand modulated antagonism of PPARgamma by genomic and non-genomic actions of
      PPARdelta.
AB  - BACKGROUND: Members of the Peroxisome Proliferator Activated Receptor, PPAR,
      subfamily of nuclear receptors display complex opposing and overlapping functions
      and a wide range of pharmacological and molecular genetic tools have been used to
      dissect their specific functions. Non-agonist bound PPARdelta has been shown to
      repress PPAR Response Element, PPRE, signalling and several lines of evidence
      point to the importance of PPARdelta repressive actions in both cardiovascular
      and cancer biology. METHODOLOGY/PRINCIPAL FINDINGS: In this report we have
      employed transient transfections and luciferase reporter gene technology to study
      the repressing effects of PPARdelta and two derivatives thereof. We demonstrate
      for the first time that the classical dominant negative deletion of the
      Activation Function 2, AF2, domain of PPARdelta show enhanced repression of PPRE
      signalling in the presence of a PPARdelta agonist. We propose that the mechanism
      for the phenomenon is increased RXR heterodimerisation and DNA binding upon
      ligand binding concomitant with transcriptional co-repressor binding. We also
      demonstrated ligand-dependent dominant negative action of a DNA non-binding
      derivative of PPARdelta on PPARgamma1 signalling. This activity was abolished
      upon over-expression of RXRalpha suggesting a role for PPAR/cofactor competition
      in the absence of DNA binding. CONCLUSIONS/SIGNIFICANCE: These findings are
      important in understanding the wide spectrum of molecular interactions in which
      PPARdelta and PPARgamma have opposing biological roles and suggest novel
      paradigms for the design of different functional classes of nuclear receptor
      antagonist drugs.

PMID- 19756149
TI  - Differentiation of gram-negative bacterial aerosol exposure using detected
      markers in bronchial-alveolar lavage fluid.
AB  - The identification of biosignatures of aerosol exposure to pathogens has the
      potential to provide useful diagnostic information. In particular, markers of
      exposure to different types of respiratory pathogens may yield diverse sets of
      markers that can be used to differentiate exposure. We examine a mouse model of
      aerosol exposure to known Gram negative bacterial pathogens, Francisella
      tularensis novicida and Pseudomonas aeruginosa. Mice were subjected to either a
      pathogen or control exposure and bronchial alveolar lavage fluid (BALF) was
      collected at four and twenty four hours post exposure. Small protein and peptide
      markers within the BALF were detected by matrix assisted laser
      desorption/ionization (MALDI) mass spectrometry (MS) and analyzed using both
      exploratory and predictive data analysis methods; principle component analysis
      and degree of association. The markers detected were successfully used to
      accurately identify the four hour exposed samples from the control samples. This
      report demonstrates the potential for small protein and peptide marker profiles
      to identify aerosol exposure in a short post-exposure time frame.

PMID- 19756150
TI  - A novel copper chelate modulates tumor associated macrophages to promote anti
      tumor response of T cells.
AB  - BACKGROUND: At the early stages of carcinogenesis, the induction of tumor
      specific T cell mediated immunity seems to block the tumor growth and give
      protective anti-tumor immune response. However, tumor associated macrophages
      (TAMs) might play an immunosuppressive role and subvert this anti tumor immunity
      leading to tumor progression and metastasis. METHODOLOGY/PRINCIPAL FINDINGS: The
      Cu (II) complex, (chelate), copper N-(2-hydroxy acetophenone) glycinate (CuNG),
      synthesized by us, has previously been shown to have a potential usefulness in
      immunotherapy of multiple drug resistant cancers. The current study demonstrates
      that CuNG treatment of TAMs modulates their status from immunosuppressive to
      proimmunogenic nature. Interestingly, these activated TAMs produced high levels
      of IL-12 along with low levels of IL-10 that not only allowed strong Th1 response
      marked by generation of high levels of IFN-gamma but also reduced activation
      induced T cell death. Similarly, CuNG treatment of peripheral blood monocytes
      from chemotherapy and/or radiotherapy refractory cancer patients also modulated
      their cytokine status. Most intriguingly, CuNG treated TAMs could influence
      reprogramming of TGF-beta producing CD4(+)CD25(+) T cells toward IFN-gamma
      producing T cells. CONCLUSION/SIGNIFICANCE: Our results show the potential
      usefulness of CuNG in immunotherapy of drug-resistant cancers through
      reprogramming of TAMs that in turn reprogram the T cells and reeducate the T
      helper function to elicit proper anti-tumorogenic Th1 response leading to
      effective reduction in tumor growth.

PMID- 19756151
TI  - A serological survey of infectious disease in Yellowstone National Park's canid
      community.
AB  - BACKGROUND: Gray wolves (Canis lupus) were reintroduced into Yellowstone National
      Park (YNP) after a >70 year absence, and as part of recovery efforts, the
      population has been closely monitored. In 1999 and 2005, pup survival was
      significantly reduced, suggestive of disease outbreaks. METHODOLOGY/PRINCIPAL
      FINDINGS: We analyzed sympatric wolf, coyote (Canis latrans), and red fox (Vulpes
      vulpes) serologic data from YNP, spanning 1991-2007, to identify long-term
      patterns of pathogen exposure, identify associated risk factors, and examine
      evidence for disease-induced mortality among wolves for which there were survival
      data. We found high, constant exposure to canine parvovirus (wolf seroprevalence:
      100%; coyote: 94%), canine adenovirus-1 (wolf pups [0.5-0.9 yr]: 91%, adults
      [>or=1 yr]: 96%; coyote juveniles [0.5-1.5 yrs]: 18%, adults [>or=1.6 yrs]: 83%),
      and canine herpesvirus (wolf: 87%; coyote juveniles: 23%, young adults [1.6-4.9
      yrs]: 51%, old adults [>or=5 yrs]: 87%) suggesting that these pathogens were
      enzootic within YNP wolves and coyotes. An average of 50% of wolves exhibited
      exposure to the protozoan parasite, Neospora caninum, although individuals' odds
      of exposure tended to increase with age and was temporally variable. Wolf,
      coyote, and fox exposure to canine distemper virus (CDV) was temporally variable,
      with evidence for distinct multi-host outbreaks in 1999 and 2005, and perhaps a
      smaller, isolated outbreak among wolves in the interior of YNP in 2002. The years
      of high wolf-pup mortality in 1999 and 2005 in the northern region of the park
      were correlated with peaks in CDV seroprevalence, suggesting that CDV contributed
      to the observed mortality. CONCLUSIONS/SIGNIFICANCE: Of the pathogens we
      examined, none appear to jeopardize the long-term population of canids in YNP.
      However, CDV appears capable of causing short-term population declines.
      Additional information on how and where CDV is maintained and the frequency with
      which future epizootics might be expected might be useful for future management
      of the Northern Rocky Mountain wolf population.

PMID- 19756152
TI  - Comparative sequence and structural analyses of G-protein-coupled receptor
      crystal structures and implications for molecular models.
AB  - BACKGROUND: Up until recently the only available experimental (high resolution)
      structure of a G-protein-coupled receptor (GPCR) was that of bovine rhodopsin. In
      the past few years the determination of GPCR structures has accelerated with
      three new receptors, as well as squid rhodopsin, being successfully crystallized.
      All share a common molecular architecture of seven transmembrane helices and can
      therefore serve as templates for building molecular models of homologous GPCRs.
      However, despite the common general architecture of these structures key
      differences do exist between them. The choice of which experimental GPCR
      structure(s) to use for building a comparative model of a particular GPCR is
      unclear and without detailed structural and sequence analyses, could be
      arbitrary. The aim of this study is therefore to perform a systematic and
      detailed analysis of sequence-structure relationships of known GPCR structures.
      METHODOLOGY: We analyzed in detail conserved and unique sequence motifs and
      structural features in experimentally-determined GPCR structures. Deeper insight
      into specific and important structural features of GPCRs as well as valuable
      information for template selection has been gained. Using key features a workflow
      has been formulated for identifying the most appropriate template(s) for building
      homology models of GPCRs of unknown structure. This workflow was applied to a set
      of 14 human family A GPCRs suggesting for each the most appropriate template(s)
      for building a comparative molecular model. CONCLUSIONS: The available crystal
      structures represent only a subset of all possible structural variation in family
      A GPCRs. Some GPCRs have structural features that are distributed over different
      crystal structures or which are not present in the templates suggesting that
      homology models should be built using multiple templates. This study provides a
      systematic analysis of GPCR crystal structures and a consistent method for
      identifying suitable templates for GPCR homology modelling that will help to
      produce more reliable three-dimensional models.

PMID- 19756153
TI  - Association between KCNJ6 (GIRK2) gene polymorphisms and postoperative analgesic
      requirements after major abdominal surgery.
AB  - Opioids are commonly used as effective analgesics for the treatment of acute and
      chronic pain. However, considerable individual differences have been widely
      observed in sensitivity to opioid analgesics. We focused on a G-protein-activated
      inwardly rectifying potassium (GIRK) channel subunit, GIRK2, that is an important
      molecule in opioid transmission. In our initial polymorphism search, a total of
      nine single-nucleotide polymorphisms (SNPs) were identified in the whole exon, 5'
      flanking, and exon-intron boundary regions of the KCNJ6 gene encoding GIRK2.
      Among them, G-1250A and A1032G were selected as representative SNPs for further
      association studies. In an association study of 129 subjects who underwent major
      open abdominal surgery, the A/A genotype in the A1032G SNP and -1250G/1032A
      haplotype were significantly associated with increased postoperative analgesic
      requirements compared with other genotypes and haplotypes. The total dose (mean+/
      SEM) of rescue analgesics converted to equivalent oral morphine doses was 20.45+/
      9.27 mg, 10.84+/-2.24 mg, and 13.07+/-2.39 mg for the A/A, A/G, and G/G genotypes
      in the A1032G SNP, respectively. Additionally, KCNJ6 gene expression levels in
      the 1032A/A subjects were significantly decreased compared with the 1032A/G and
      1032G/G subjects in a real-time quantitative PCR analysis using human brain
      tissues, suggesting that the 1032A/A subjects required more analgesics because of
      lower KCNJ6 gene expression levels and consequently insufficient analgesic
      effects. The results indicate that the A1032G SNP and G-1250A/A1032G haplotype
      could serve as markers that predict increased analgesic requirements. Our
      findings will provide valuable information for achieving satisfactory pain
      control and open new avenues for personalized pain treatment.

PMID- 19756154
TI  - Anesthetics rapidly promote synaptogenesis during a critical period of brain
      development.
AB  - Experience-driven activity plays an essential role in the development of brain
      circuitry during critical periods of early postnatal life, a process that depends
      upon a dynamic balance between excitatory and inhibitory signals. Since general
      anesthetics are powerful pharmacological modulators of neuronal activity, an
      important question is whether and how these drugs can affect the development of
      synaptic networks. To address this issue, we examined here the impact of
      anesthetics on synapse growth and dynamics. We show that exposure of young
      rodents to anesthetics that either enhance GABAergic inhibition or block NMDA
      receptors rapidly induce a significant increase in dendritic spine density in the
      somatosensory cortex and hippocampus. This effect is developmentally regulated;
      it is transient but lasts for several days and is also reproduced by selective
      antagonists of excitatory receptors. Analyses of spine dynamics in hippocampal
      slice cultures reveals that this effect is mediated through an increased rate of
      protrusions formation, a better stabilization of newly formed spines, and leads
      to the formation of functional synapses. Altogether, these findings point to
      anesthesia as an important modulator of spine dynamics in the developing brain
      and suggest the existence of a homeostatic process regulating spine formation as
      a function of neural activity. Importantly, they also raise concern about the
      potential impact of these drugs on human practice, when applied during critical
      periods of development in infants.

PMID- 19756155
TI  - Comparison of the immunomodulatory properties of three probiotic strains of
      Lactobacilli using complex culture systems: prediction for in vivo efficacy.
AB  - BACKGROUND: While the use of probiotics to treat or prevent inflammatory bowel
      disease (IBD) has been proposed, to this point the clinical benefits have been
      limited. In this report we analyzed the immunological activity of three strains
      of Lactobacillus to predict their in vivo efficacy in protecting against
      experimental colitis. METHODOLOGY/PRINCIPAL FINDINGS: We compared the
      immunological properties of Lactobacillus plantarum NCIMB8826, L. rhamnosus GG
      (LGG), L. paracasei B21060 and pathogenic Salmonella typhimurium (SL1344). We
      studied the stimulatory effects of these different strains upon dendritic cells
      (DCs) either directly by co-culture or indirectly via conditioning of an
      epithelial intermediary. Furthermore, we characterized the effects of these
      strains in vivo using a Dextran sulphate sodium (DSS) model of colitis. We found
      that the three strains exhibited different abilities to induce inflammatory
      cytokine production by DCs with L. plantarum being the most effective followed by
      LGG and L. paracasei. L. paracasei minimally induced the release of cytokines,
      while it also inhibited the potential of DCs to both produce inflammatory
      cytokines (IL-12 and TNF-alpha) and to drive Th1 T cells in response to
      Salmonella. This effect on DCs was found under both direct and indirect
      stimulatory conditions - i.e. mediated by epithelial cells - and was dependent
      upon an as yet unidentified soluble mediator. When tested in vivo, L. plantarum
      and LGG exacerbated the development of DSS-induced colitis and caused the death
      of treated mice, while, conversely L. paracasei was protective. CONCLUSIONS: We
      describe a new property of probiotics to either directly or indirectly inhibit DC
      activation by inflammatory bacteria. Moreover, some immunostimulatory probiotics
      not only failed to protect against colitis, they actually amplified the disease
      progression. In conclusion, caution must be exercised when choosing a probiotic
      strain to treat IBD.

PMID- 19756156
TI  - Theoretical study for high-energy-density compounds derived from
      cyclophosphazene. IV. DFT studies on 1,1-diamino-3,3,5,5,7,7
      hexaazidocyclotetraphosphazene and its isomers.
AB  - In the present study, a theoretical study of 1,1
      diaminohexaazidocyclotetraphophazene (DAHA) and its isomers has been performed,
      using quantum computational density functional theory (B3LYP and B3PW91 methods)
      with 6-31G* and 6-31G** basis sets implemented in Gaussian 03 program suite.
      Molecular structure and bonding, vibrational frequencies, Milliken population
      analysis, and natural bond orbit (NBO) have been studied. The heats of formation
      from atomization energies have also been calculated based on the optimized
      geometry. The obtained heats of formation data are compared with their homologous
      cyclophosphazene in order to demonstrate the accuracy of the methods, which
      indicate that the studied compounds might be potentially used as high energetic
      materials. In addition, the relative stability of five isomers have been deduced
      based on the total energy and the gap of frontier orbital energies.

PMID- 19756157
TI  - Enrichment from birth accelerates the functional and cellular development of a
      motor control area in the mouse.
AB  - BACKGROUND: There is strong evidence that sensory experience in early life has a
      profound influence on the development of sensory circuits. Very little is known,
      however, about the role of experience in the early development of striatal
      networks which regulate both motor and cognitive function. To address this, we
      have investigated the influence of early environmental enrichment on motor
      development. METHODOLOGY/PRINCIPAL FINDINGS: Mice were raised in standard or
      enriched housing from birth. For animals assessed as adults, half of the mice had
      their rearing condition reversed at weaning to enable the examination of the
      effects of pre- versus post-weaning enrichment. We found that exclusively pre
      weaning enrichment significantly improved performance on the Morris water maze
      compared to non-enriched mice. The effects of early enrichment on the emergence
      of motor programs were assessed by performing behavioural tests at postnatal day
      10. Enriched mice traversed a significantly larger region of the test arena in an
      open-field test and had improved swimming ability compared to non-enriched
      cohorts. A potential cellular correlate of these changes was investigated using
      Wisteria-floribunda agglutinin (WFA) staining to mark chondroitin-sulfate
      proteoglycans (CSPGs). We found that the previously reported transition of CSPG
      staining from striosome-associated clouds to matrix-associated perineuronal nets
      (PNNs) is accelerated in enriched mice. CONCLUSIONS/SIGNIFICANCE: This is the
      first demonstration that the early emergence of exploratory as well as
      coordinated movement is sensitive to experience. These behavioural changes are
      correlated with an acceleration of the emergence of striatal PNNs suggesting that
      they may consolidate the neural circuits underlying these behaviours. Finally, we
      confirm that pre-weaning experience can lead to life long changes in the learning
      ability of mice.

PMID- 19756158
TI  - Predicting positive p53 cancer rescue regions using Most Informative Positive
      (MIP) active learning.
AB  - Many protein engineering problems involve finding mutations that produce proteins
      with a particular function. Computational active learning is an attractive
      approach to discover desired biological activities. Traditional active learning
      techniques have been optimized to iteratively improve classifier accuracy, not to
      quickly discover biologically significant results. We report here a novel active
      learning technique, Most Informative Positive (MIP), which is tailored to
      biological problems because it seeks novel and informative positive results. MIP
      active learning differs from traditional active learning methods in two ways: (1)
      it preferentially seeks Positive (functionally active) examples; and (2) it may
      be effectively extended to select gene regions suitable for high throughput
      combinatorial mutagenesis. We applied MIP to discover mutations in the tumor
      suppressor protein p53 that reactivate mutated p53 found in human cancers. This
      is an important biomedical goal because p53 mutants have been implicated in half
      of all human cancers, and restoring active p53 in tumors leads to tumor
      regression. MIP found Positive (cancer rescue) p53 mutants in silico using 33%
      fewer experiments than traditional non-MIP active learning, with only a minor
      decrease in classifier accuracy. Applying MIP to in vivo experimentation yielded
      immediate Positive results. Ten different p53 mutations found in human cancers
      were paired in silico with all possible single amino acid rescue mutations, from
      which MIP was used to select a Positive Region predicted to be enriched for p53
      cancer rescue mutants. In vivo assays showed that the predicted Positive Region:
      (1) had significantly more (p<0.01) new strong cancer rescue mutants than control
      regions (Negative, and non-MIP active learning); (2) had slightly more new strong
      cancer rescue mutants than an Expert region selected for purely biological
      considerations; and (3) rescued for the first time the previously unrescuable p53
      cancer mutant P152L.

PMID- 19756159
TI  - Effect of Hibiscus sabdariffa L. dried calyx ethanol extract on fat absorption
      excretion, and body weight implication in rats.
AB  - The effect of Hibiscus sabdariffa L. (Hs) calyx extract on fat absorption
      excretion and body weight in rats, was investigated. Rats were fed with either a
      basal diet (SDC = Control diet) or the same diet supplemented with Hs extracts at
      5%, 10% and 15% (SD(5), SD(10) and SD(15)). Only SD(5) did not show significant
      increases in weight, food consumption and efficiency compared to SD(C). The
      opposite occurred in SD(15) group which showed a significant decrease for these
      three parameters. The SD(10) responses were similar to SD(15), with the exception
      of food consumption. In both SD(C) and SD(5) groups, no body weight loss was
      observed; however, only in the latter group was there a significantly greater
      amount of fatty acids found in feces. A collateral effect emerging from the study
      is that components of Hs extract at the intermediate and greater concentrations
      used in this experiment could be considered possible antiobesity agents.

PMID- 19756160
TI  - Differential proteome analysis of the preeclamptic placenta using optimized
      protein extraction.
AB  - The human placenta is a difficult tissue to work with using proteomic technology
      since it contains large amounts of lipids and glycogen. Both lipids and glycogen
      are known to interfere with the first step in the two-dimensional polyacrylamide
      gel electrophoresis (2D-PAGE), the isoelectric focusing. In order to gain the
      best possible protein separation on 2D-PAGE, an optimized sample preparation
      protocol for placental proteins was developed. Two different buffers, urea/CHAPS
      and Hepes, were used for solubilization in combination with six different
      precipitation methods. The removal of glycogen from the samples by centrifugation
      was crucial for the final proteome maps. Solubilization with urea/CHAPS in
      combination with dichloromethane/methanol or acidified acetone proved to be the
      best precipitation procedures. When applied to clinical placenta samples
      apolipoprotein A1 was found to be accumulated in the preeclamptic placenta, where
      it may either have a nutritional effect or act as a modifier of signal
      transduction.

PMID- 19756161
TI  - Multiple sclerosis lesion detection using constrained GMM and curve evolution.
AB  - This paper focuses on the detection and segmentation of Multiple Sclerosis (MS)
      lesions in magnetic resonance (MRI) brain images. To capture the complex tissue
      spatial layout, a probabilistic model termed Constrained Gaussian Mixture Model
      (CGMM) is proposed based on a mixture of multiple spatially oriented Gaussians
      per tissue. The intensity of a tissue is considered a global parameter and is
      constrained, by a parameter-tying scheme, to be the same value for the entire set
      of Gaussians that are related to the same tissue. MS lesions are identified as
      outlier Gaussian components and are grouped to form a new class in addition to
      the healthy tissue classes. A probability-based curve evolution technique is used
      to refine the delineation of lesion boundaries. The proposed CGMM-CE algorithm is
      used to segment 3D MRI brain images with an arbitrary number of channels. The
      CGMM-CE algorithm is automated and does not require an atlas for initialization
      or parameter learning. Experimental results on both standard brain MRI simulation
      data and real data indicate that the proposed method outperforms previously
      suggested approaches, especially for highly noisy data.

PMID- 19756162
TI  - Effects of efforts to intensify management on blood pressure control among
      patients with type 2 diabetes mellitus and hypertension: a pilot study.
AB  - There continues to be a need for improved medical management of diabetes patients
      with hypertension in primary care. While several care models have shown
      effectiveness in achieving various outcomes among these patients, it remains
      unclear what care model is most effective in improving blood pressure control in
      primary care. In this prospective study, 54 patients with type 2 diabetes
      mellitus and blood pressure of >140/90 identified through the registry, were
      randomized into three groups. Group A attended a nurse educator-conducted class
      on diabetes and hypertension, group B attended the same class and was asked to
      monitor their home blood pressure using provided device, and group C served as
      control (usual care). Of the 24 subjects who completed the study, only 20%
      achieved the target blood pressure of <130/80 and there was no statistical
      difference in mean systolic and diastolic blood pressures among the three groups
      (p > 0.05). Efforts to intensify management of hypertension among type 2 diabetes
      patients did not result in better blood pressure control compared to usual care.
      Studies looking into factors which limit patients' participation in group classes
      and determining patients' preferences in disease management would be helpful in
      ensuring success of any chronic disease management program.

PMID- 19756163
TI  - Cardiovascular disease in patients with chronic kidney disease.
AB  - Patients with chronic kidney disease have a high burden of cardiovascular
      morbidity and mortality. The vast majority of patients with chronic kidney
      disease do not progress to end stage renal failure, but do have a significantly
      higher incidence of all cardiovascular co-morbidities. Traditional cardiovascular
      risk factors only partially account for this increased incidence of
      cardiovascular disease. In patients with kidney disease the basic biology
      underlying cardiovascular disease may be similar to that in patients without
      kidney disease, but it would seem many more risk factors are involved as a
      consequence of renal dysfunction. Although emphasis is placed on delaying the
      progression of chronic kidney disease, it must be appreciated that for many
      patients it is vital to address their cardiovascular risk factors at an early
      stage to prevent premature cardiovascular death. This review examines available
      epidemiological evidence, discusses common cardiovascular risk factors in
      patients with chronic kidney disease, and suggests possible treatment strategies.
      Potential areas for important research are also described.

PMID- 19756164
TI  - Blood pressure goal achievement with olmesartan medoxomil-based treatment:
      additional analysis of the OLMEBEST study.
AB  - AIMS: Guidelines recommend blood pressure (BP) in hypertensive patients should be
      <140 systolic BP (SBP) and <90 diastolic BP (DBP) mmHg. This analysis assessed
      goal rate achievement in hypertensive patients receiving olmesartan-based
      treatment in the OLMEBEST study. METHODS: Patients with essential hypertension
      (DBP > or = 90 mmHg and <110 mmHg) received open-label olmesartan medoxomil 20
      mg/day (n = 2306). After 8 weeks, patients with DBP > or = 90 mmHg (n = 627) were
      randomized to 4 weeks' double-blind treatment with olmesartan 40 mg/day
      monotherapy or olmesartan 20 mg/day plus hydrochlorothiazide (HCTZ) 12.5 mg/day.
      For this analysis, the numbers and proportions of patients who achieved SBP < 140
      mmHg and/or DBP < 90 mmHg at the end of the 4 weeks were calculated. RESULTS: In
      patients who achieved DBP normalization (<90 mmHg) at week 8 (n = 1546) and
      continued open-label olmesartan 20 mg/day, 66.7% achieved SBP/DBP < 140/90 mmHg
      at Week 12. In patients who did not achieve DBP normalization at Week 8, 26.8% of
      those randomized to olmesartan 40 mg/day and 42.5% of those randomized to
      olmesartan 20 mg/day plus HCTZ 12.5 mg/day achieved a SBP/DBP < 140/90 mmHg at
      Week 12. CONCLUSION: Olmesartan 40 mg/day and olmesartan 20 mg/day plus HCTZ 12.5
      mg/day allow substantial proportions of patients to achieve BP goals.

PMID- 19756165
TI  - Metabolic syndrome and cardiovascular disease in South Asians.
AB  - This review discusses the prevalence of metabolic syndrome and cardiovascular
      disease in the South Asian population, evaluates conventional and emerging risk
      factors, and reinforces the need for ethnic-specific redefinition of guidelines
      used to diagnose metabolic syndrome. We reviewed recent and past literature using
      Ovid Medline and PubMed databases. South Asians represent one of the largest and
      fastest growing ethnic groups in the world. With this growth, a dramatic rise in
      the rates of acute myocardial infarction and diabetes is being seen in this
      population. Potential etiologies for this phenomenon include dietary
      westernization, poor lifestyle measures, adverse body fat patterning, and
      genetics. While traditional risk factors for diabetes and cardiovascular disease
      should not be overlooked, early metabolic syndrome has now been shown in the
      South Asian pediatric population, suggesting that "metabolic programming" and
      perinatal influences may likely play a substantial role. Health care
      practitioners must be aware that current guidelines used to identify individuals
      with metabolic syndrome are underestimating South Asian individuals at risk. New
      ethnic-specific guidelines and prevention strategies are discussed in this review
      and should be applied by clinicians to their South Asian patients.

PMID- 19756166
TI  - Complementary and Alternative Medicine Use and Diabetes Self-Management Among
      Rural Older Adults.
AB  - Complementary and alternative medicine (CAM) is a growing form of self-care and
      is related to other healthy behaviors. This study examines the relationship
      between CAM use and diabetes self-management. A survey of rural older African
      American, Native American, and White adults with diabetes was conducted. Data
      were collected on diabetes self-management domains and general and diabetes
      specific CAM use. Some associations were observed, particularly for CAM use and
      following a healthy eating plan. CAM is part of the health maintenance strategy
      of rural older adults with diabetes. Further research should examine the health
      trajectory associated with CAM use in this population.

PMID- 19756167
TI  - Nutritional analysis of a fiesta on Guam.
AB  - Fiestas in Guam are celebrated year round, but documentation of the preparation
      and nutritional components of foods served at a traditional fiesta on Guam is
      limited. Food preparation was observed during a fiesta celebrated in the village
      of Sinajana, Guam. A food scale was used to weigh the ingredients of food dishes.
      Nutritional analysis software was used to determine the nutrient content of each
      food dish served. Of the thirty-four dishes that were prepared and served, 32
      dishes were analyzed. These dishes comprised 609,210 kcal, 38,761 g protein,
      42,883 g carbohydrates, 30,260 g total fat, 10,019 g saturated fat, and 1890 g
      dietary fiber. More than 95% of the food prepared was potentially consumed. Of
      the food potentially consumed, 24% of the energy was from protein, 29% of the
      energy was from carbohydrates, 45% of the energy was from total fat, and 15% of
      the energy was from saturated fat. Of the top 10 foods contributing the most
      energy, 8 were totche (fish and meat) dishes. The nutrient availability for
      fiesta-goers was estimated. The assessment of fiesta nutrient intake is
      recommended for future research.

PMID- 19756168
TI  - The median is not the only message: a clinician's perspective on mathematical
      analysis of glycemic variability and modeling in diabetes mellitus.
AB  - Hemoglobin A1c (HbA1c), a long-term, integrated average of tissue exposure to
      hyperglycemia, is the best reflection of average glucose concentrations and the
      best proven predictor of microvascular complications of diabetes mellitus.
      However, HbA1c fails to capture glycemic variability and the risks associated
      with extremes of hypoglycemia and hyperglycemia. These risks are the primary
      barrier to achieving the level of average glucose control that will minimize both
      the microvascular and the long-term macrovascular complications of type 1
      diabetes. High blood glucose levels largely due to prandial excursions produce
      oxidative and inflammatory stress with potential acceleration of preexisting
      atherosclerosis and increased cardiovascular risk. Moreover, some temporal
      aspects of glycemic variation, including the rates of rise and fall of glucose,
      are associated with adverse cognitive and mood symptoms in those with diabetes.
      Methods to quantify the risk of glycemic extremes, both high and low, and the
      variability including its temporal aspects are now more precise than ever. These
      important endpoints should be included for use in clinical trials as useful
      metrics and recognized by regulatory agencies, which has not been the case in the
      past. Precise evaluation of glycemic variability and its attendant risks are
      essential in the design of optimal therapies; for these reasons, inclusion of
      these metrics and the pulsatile hormone patterns in mathematical models may be
      essential. For the clinician, the incursion of mathematical models that simulate
      normal and pathophysiological mechanisms of glycemic control is a reality and
      should be also gradually incorporated into clinical practice.

PMID- 19756169
TI  - The moral organization of the professions: Bioethics in the United States and
      France.
AB  - Bioethics is a relatively new endeavor, emerging as a discourse distinct from
      considerations of moral responsibility occurring within the professions of
      medicine and science. We use the 'de-centered comparative method' to examine how
      the emergence and development of bioethics varies across different social and
      cultural settings. In particular, we look at bioethical work in the United States
      and France, exploring these different manifestations of the movement toward
      external oversight of those working in medicine and the life sciences. The study
      of these varied processes of occupational development allows us to address two
      important issues. One is the way in which pathways of professionalisation are
      shaped by contingent cultural and historical factors. The other is the degree to
      which the increasing prominence of the bioethical occupation is the result of the
      professional desires of bioethicists and/or a concern for the public good.

PMID- 19756170
TI  - Cavitation selectively reduces the negative-pressure phase of lithotripter shock
      pulses.
AB  - Measurements using a fiber-optic probe hydrophone, high-speed camera, and B-mode
      ultrasound showed attenuation of the trailing negative-pressure phase of a
      lithotripter shock pulse under conditions that favor generation of cavitation
      bubbles, such as in water with a high content of dissolved gas or at high pulse
      repetition rate where more cavitation nuclei persisted between pulses. This
      cavitation-mediated attenuation of the acoustic pulse was also observed to
      increase with increasing amplitude of source discharge potential, such that the
      negative-pressure phase of the pulse can remain fixed in amplitude even with
      increasing source discharge potential.

PMID- 19756171
TI  - Who is Retained in First Grade? A Psychosocial Perspective.
AB  - A sample of 784 children with below-median literacy performance in kindergarten
      or at the beginning of grade 1 was assessed in 5 areas of psychological and
      social variables: academic competence, sociodemographic characteristics,
      social/emotional/behavioral characteristics, school context, and home
      environment. We examined the contribution of academic competence to retention
      first, and then evaluated contributions of each of the other areas beyond
      academic competence. The 165 students retained in first grade were found to
      differ from promoted students on reading and mathematics achievement test scores,
      teacher-rated engagement and achievement, and intelligence as individual
      predictors of academic competence, but with direct effects only for reading and
      teacher-rated achievement when entered as a set of predictors. None additional
      variables had zero-order significant correlations with retention status. Using
      hierarchical logistic regression, beyond the effects of academic competence
      variables we found that only being underage for grade and the home environmental
      variables of positive parental perceptions of their child's school, sense of
      shared responsibility for education with the school, and parent communication
      with the school contributed significantly to retention. Implications for
      educational policy and intervention are discussed.

PMID- 19756172
TI  - Pathways to Assisted Living: The Influence of Race and Class.
AB  - This article examines how race and class influence decisions to move to assisted
      living facilities. Qualitative methods were used to study moving decisions of
      residents in 10 assisted living facilities varying in size and location, as well
      as race and socioeconomic status of residents. Data were derived from in-depth
      interviews with 60 residents, 43 family members and friends, and 12
      administrators. Grounded theory analysis identified three types of residents
      based on their decision-making control: proactive, compliant, and
      passive/resistant. Only proactive residents (less than a quarter of residents)
      had primary control. Findings show that control of decision making for elders who
      are moving to assisted living is influenced by class, though not directly by
      race. The impact of class primarily related to assisted-living placement options
      and strategies available to forestall moves. Factors influencing the decision
      making process were similar for Black and White elders of comparable
      socioeconomic status.

PMID- 19756173
TI  - Human Low Density Lipoprotein (LDL) and Human Serum Albumin (HSA) Co-Adsorption
      Onto the C18-Silica Gradient Surface.
AB  - Co-adsorption kinetics of human low density lipoprotein (LDL) and serum albumin
      (HSA) on hydrophilic/hydrophobic gradient silica surface were studied using Total
      Internal Reflection Fluorescence (TIRF) and autoradiography. Two experimental
      systems were examined: (1) fluorescein-labeled LDL (FITC-LDL) adsorption from a
      FITC-LDL + HSA solution mixture onto the octadecyldi-methylsilyl (C18)-silica
      gradient surface, and (2) the FITC-LDL adsorption onto the HSA pre-adsorbed on
      the C18-silica gradient surface. Experiments with fluorescein-labeled albumin
      (FITC-HSA) and unlabeled LDL have been performed in parallel. The adsorption
      kinetics of FITC-LDL onto the hydrophilic silica was found to be transport
      limited and not affected by co-adsorption of HSA. A slower adsorption kinetics of
      lipoprotein onto the silica with pre-adsorbed HSA layer resulted from a slow
      appearance of LDL binding sites exposed by the process of HSA desorption. In the
      region of increasing surface density of C18 groups, the FITC-LDL adsorption rate
      fell below the transport-limited adsorption rate, except in the very early
      adsorption times. Pre-adsorption of HSA onto the C18-silica gradient region
      resulted in a significant decrease of both the FITC-LDL adsorption rate and
      adsorbed amount. The lowest FITC-LDL adsorption was found in the region of C18
      self-assembled monolayer, where the pre-adsorbed HSA layer almost completely
      eliminated lipoprotein binding.

PMID- 19756175
TI  - The Role of the Family Context in the Development of Emotion Regulation.
AB  - This article reviews current literature examining associations between components
      of the family context and children and adolescents' emotion regulation (ER). The
      review is organized around a tripartite model of familial influence. Firstly, it
      is posited that children learn about ER through observational learning, modeling
      and social referencing. Secondly, parenting practices specifically related to
      emotion and emotion management affect ER. Thirdly, ER is affected by the
      emotional climate of the family via parenting style, the attachment relationship,
      family expressiveness and the marital relationship. The review ends with
      discussions regarding the ways in which child characteristics such as negative
      emotionality and gender affect ER, how socialization practices change as children
      develop into adolescents, and how parent characteristics such as mental health
      affect the socialization of ER.

PMID- 19756177
TI  - Enhanced wettability of SU-8 photoresist through a photografting procedure for
      bioanalytical device applications.
AB  - In this work, we detail a method whereby a polymeric hydrogel layer is grafted to
      the negative tone photoresist SU-8 in order to improve its wettability. A
      photoinitiator is first immobilized on freshly prepared SU-8 samples, acting as
      the starting point for various surface modifications strategies. Grafting of a 2
      hydroxyethylmethacrylate-based hydrogel from the SU-8 surface resulted in the
      reduction of the static contact angle of a water droplet from 79 +/- 1 degrees to
      36 +/- 1 degrees , while addition of a poly(ethylene glycol)-rich hydrogel layer
      resulted in further improvement (8 +/- 1 degrees ). Wettability is greatly
      enhanced after 30 minutes of polymerization, with a continued but more gradual
      decrease in contact angle up to approximately 50 minutes. Hydrogel formation is
      triggered by exposure to UV irradiation, allowing for the formation of
      photopatterned structures using existing photolithographic techniques.

PMID- 19756176
TI  - 2007 AIChE Alpha Chi Sigma Award: From Material to Tissue: Biomaterial
      Development, Scaffold Fabrication, and Tissue Engineering.
AB  - The need for techniques to facilitate the regeneration of failing or destroyed
      tissues remains great with the aging of the worldwide population and the
      continued incidence of trauma and diseases such as cancer. A 16-year history in
      biomaterial scaffold development and tissue engineering is examined, beginning
      with the synthesis of novel materials and fabrication of 3D porous scaffolds.
      Exploring cell-scaffold interactions and subsequently cellular delivery using
      biomaterial carriers, we have developed a variety of techniques for bone and
      cartilage engineering. In addition to delivering cells, we have utilized growth
      factors, DNA, and peptides to improve the in vitro and in vivo regeneration of
      tissues. This review covers important developments and discoveries within our
      laboratory, and the increasing breadth in the scope of our work within the
      expanding field of tissue engineering is presented.

PMID- 19756178
TI  - Polymer-supported lipid shells, onions, and flowers.
AB  - Phospholipid-enveloped biodegradable polymer microparticles and nanoparticles
      synthesized by an emulsion/solvent evaporation process were characterized by
      confocal and cryoelectron microscopies to show that the lipid envelope exhibits
      two-dimensional fluidity and can be configured into 'shell', 'onion', or 'flower'
      nanostructures, depending on the quantity and composition of lipids employed in
      the synthesis.

PMID- 19756179
TI  - The GJA8 allele encoding CX50I247M is a rare polymorphism, not a cataract-causing
      mutation.
AB  - PURPOSE: The aim of this study was the genetic, cellular, and physiological
      characterization of a connexin50 (CX50) variant identified in a child with
      congenital cataracts. METHODS: Lens material from surgery was collected and used
      for cDNA production. Genomic DNA was prepared from blood obtained from the
      proband and her parents. PCR amplified DNA fragments were sequenced and
      characterized by restriction digestion. Connexin protein distribution was studied
      by immunofluorescence in transiently transfected HeLa cells. Formation of
      functional channels was assessed by two-microelectrode voltage-clamp in cRNA
      injected Xenopus oocytes. RESULTS: Ophthalmologic examination showed that the
      proband suffered from bilateral white, diffuse cataracts, but the parents were
      free of lens opacities. Direct sequencing of the PCR product produced from lens
      cDNA showed that the proband was heterozygous for a G>T transition at position
      741 of the GJA8 gene, encoding the exchange of methionine for isoleucine at
      position 247 of CX50 (CX50I247M). The mutation was confirmed in the genomic DNA,
      but it was also present in the unaffected mother. When expressed in HeLa cells,
      both wild type CX50 and CX50I247M formed gap junction plaques. Both CX50 and
      CX50I247M induced gap junctional currents in pairs of Xenopus oocytes.
      CONCLUSIONS: Although the CX50I247M substitution has previously been suggested to
      cause cataracts, our genetic, cellular, and electrophysiological data suggest
      that this allele more likely represents a rare silent, polymorphic variant.

PMID- 19756180
TI  - Decursin inhibits retinal neovascularization via suppression of VEGFR-2
      activation.
AB  - PURPOSE: Pathologic angiogenesis in the retina leads to the catastrophic loss of
      vision. Retinopathy of prematurity (ROP), a vasoproliferative retinopathy, is a
      leading cause of blindness in children. We evaluated the inhibitory effect of
      decursin on retinal neovascularization. METHODS: Anti-angiogenic activity of
      decursin was evaluated by vascular endothelial growth factor (VEGF)-induced
      proliferation, migration, and in vitro tube formation assay of human retinal
      microvascular endothelial cells (HRMECs). We also used western blot analysis to
      assess inhibition of vascular endothelial growth factor receptor-2 (VEGFR-2)
      phosphorylation by decursin. After intravitreal injection of decursin in a mouse
      model of ROP, retinal neovascularization was examined by fluorescence angiography
      and vessel counting in cross-sections. The toxicity of decursin was evaluated
      through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay
      in HRMECs as well as histologic and immunohistochemistry examination for glial
      fibrillary acidic protein in the retina. RESULTS: Decursin significantly
      inhibited VEGF-induced proliferation, migration, and the formation of capillary
      like networks of retinal endothelial cells in a dose-dependent manner. Decursin
      inhibited VEGF-induced phosphorylation of VEGFR-2, blocking the VEGFR-2 signaling
      pathway. When intravitreously injected, decursin dramatically suppressed retinal
      neovascularization in a mouse model of ROP. Even in a high concentration,
      decursin never induced any structural or inflammatory changes to cells in retinal
      or vitreous layers. Moreover, the upregulation of glial fibrillary acidic protein
      expression was not detected in Mueller cells. CONCLUSIONS: Our data suggest that
      decursin may be a potent anti-angiogenic agent targeting the VEGFR-2 signaling
      pathway, which significantly inhibits retinal neovascularization without retinal
      toxicity and may be applicable in various other vasoproliferative retinopathies
      as well.

PMID- 19756181
TI  - AAV retinal transduction in a large animal model species: comparison of a self
      complementary AAV2/5 with a single-stranded AAV2/5 vector.
AB  - PURPOSE: To compare self-complementary (sc) and single-stranded (ss) adeno
      associated viral 2/5 (AAV2/5) vectors for retinal cell transduction in the dog
      when delivered by subretinal injection. METHODS: ScAAV2/5 and ssAAV2/5 vectors
      encoding enhanced green fluorescent protein (GFP) under control of the chicken
      beta actin promoter were prepared to the same titer. Equal amounts of viral
      particles were delivered into the subretinal spaces of both eyes of two dogs. In
      each dog, one eye received the scAAV2/5 and the other the ssAAV2/5. In vivo
      expression of GFP was monitored ophthalmoscopically. The dogs were sacrificed,
      and their retinas were examined by fluorescent microscopy and
      immunohistochemistry to determine GFP expression patterns and to assay for glial
      reactivity. RESULTS: GFP expression in the scAAV2/5 injected eyes was detectable
      at a much earlier time point than in the ssAAV2/5 injected eyes. Expression of
      GFP was also at higher levels in the scAAV2/5-injected eyes. Expression levels
      remained stable for the seven month duration of the study. The types of cells
      transduced by both vectors were similar; there was strong reporter gene
      expression in the RPE and photoreceptors, although not all cones in the
      transduced area expressed GFP. Some horizontal and Muller cells were also
      transduced. CONCLUSIONS: When delivered by subretinal injection in the dog,
      scAAV2/5 induces faster and stronger transgene expression than ssAAV2/5. The
      spectrum of retinal neurons transduced is similar between the two vectors. These
      results confirm in a large animal model those previously reported in the mouse.
      ScAAV2/5 shows promise for use in the treatment of conditions where a rapid
      transgene expression is desirable. Furthermore, it may be possible to use a lower
      number of viral particles to achieve the same effect compared with ssAAV2/5
      vectors.

PMID- 19756182
TI  - Expression of cadherin 23 isoforms is not conserved: implications for a mouse
      model of Usher syndrome type 1D.
AB  - PURPOSE: We compared cadherin 23 (Cdh23) mRNA and protein variants in the inner
      ear and retina of wild-type and mutant mice and primates to better understand the
      pleiotropic effects of Cdh23 mutations, and specifically to understand the
      absence of retinal degeneration in Cdh23 mutant mice. METHODS: Semiquantitative
      real-time PCR was used to compare the level of expression of Cdh23 alternative
      transcripts in the inner ear and retina of wild-type and homozygous Cdh23(v-6J)
      (waltzer) mice. Antibodies generated against CDH23 isoforms were used in
      immunohistochemistry, immunohistology, electron microscopy, and western blot
      analyses of mouse and primate inner ear and retina to study the distribution of
      these isoforms in various cellular compartments. RESULTS: Cdh23 mRNA alternative
      splice variants were temporally and spatially regulated in the inner ear and
      retina. In the mature mouse retina, CDH23 isoforms were broadly expressed in
      various cellular compartments of the photoreceptor layer. The wild-type CDH23_V3
      protein isoform, which has PDZ binding motifs but neither extracellular domains
      nor a transmembrane domain, localized exclusively to the outer plexiform layer of
      the retina containing photoreceptor cell synapses and to the synaptic region of
      auditory and vestibular hair cells. The longest CDH23 protein isoform, CDH23_V1,
      appeared by western blotting to be the only one affected by the Cdh23(v-6J)
      mutation; it was expressed in the wild-type mouse inner ear, but not in the mouse
      retina. However, CDH23_V1 was detected in western blot analyses of monkey and
      human retinas. CONCLUSIONS: The time- and tissue-dependent expression patterns
      that we have shown for Cdh23 alternative transcripts suggest developmental roles
      and tissue-specific functions for the various transcripts. Many of these isoforms
      continue to be expressed in waltzer mice. The longest CDH23 isoform (CDH23_V1),
      however, is not expressed in mutant mice and is necessary for normal inner ear
      function. The longest isoform is expressed in the retinas of primates, but not
      detected in the mouse retina. This species difference suggests that the mouse may
      not be a suitable model for studying the retinitis pigmentosa phenotype of human
      Usher syndrome type 1D.

PMID- 19756183
TI  - HLA-DRB1 among patients with Vogt-Koyanagi-Harada disease in Saudi Arabia.
AB  - PURPOSE: Vogt-Koyanagi-Harada (VKH) disease is an immune-mediated disorder with
      autoimmune insult directed against antigens associated with melanocytes. The
      genetic predisposition among VKH has not been explored in Saudi Arabia. So, the
      purpose of this study was to investigate the association of human leukocyte
      antigen (HLA)-DRB1 alleles to VKH patients and to clarify the molecular genetic
      mechanism underlying the susceptibility or resistance to VKH disease. METHODS:
      Genomic DNA from a total of 30 patients with VKH and 29 control subjects was
      extracted from peripheral blood, and HLA-DRB1 alleles were typed by polymerase
      chain reaction and sequence based typing (SBT). RESULTS: We found a statistically
      significant difference in the prevalence of HLA-DRB1 *0405 between the VKH
      patients and control subjects (p<0.05). Eleven out of thirty (36.6%) patients
      with VKH had positive HLA-DRB1 *0405 compared to two out of twenty-nine (6.9%)
      control subjects. However, there were no statistically significant differences in
      the HLA-DRB1 alleles *01, *0101, *0102, *0301, *04, *0403, *0404, *0701, *1001,
      *1101, *1112, *1301, *1302, *1303, *1501, and *1502 between the VKH patients and
      controls. CONCLUSIONS: Patients with VKH had significantly greater incidence of
      HLA-DRB1 *0405 when compared to age and sex-matched controls. Consequently, this
      finding suggests that HLA-DRB1 *0405 allele might play a role in the pathogenesis
      of VKH disease.

PMID- 19756184
TI  - Involvement of A(1) adenosine receptors in osmotic volume regulation of retinal
      glial cells in mice.
AB  - PURPOSE: Osmotic swelling of Muller glial cells has been suggested to contribute
      to retinal edema. We determined the role of adenosine signaling in the inhibition
      of Muller cell swelling in the murine retina. METHODS: The size of Muller cell
      somata was recorded before and during perfusion of retinal sections and isolated
      Muller cells with a hypoosmolar solution. Retinal tissues were freshly isolated
      from wild-type mice and mice deficient in A(1) adenosine receptors (A(1)AR(-/-)),
      or cultured as whole-mounts for three days. The potassium conductance of Muller
      cells was recorded in isolated cells, and retinal slices were immunostained
      against Kir4.1. RESULTS: Hypotonic exposure for 4 min induced a swelling of
      Muller cell bodies in retinal slices from A(1)AR(-/-) mice but not wild-type
      mice. Pharmacological inhibition of A(1) receptors or of the ecto-5'-nucleotidase
      induced hypoosmotic swelling of Muller cells from wild-type mice. Exogenous
      adenosine prevented the swelling of Muller cells from wild-type but not A(1)AR(-/
      ) mice. The antiinflammatory corticosteroid, triamcinolone acetonide, inhibited
      the swelling of Muller cells from wild-type mice; this effect was blocked by an
      antagonist of A(1) receptors. The potassium conductance of Muller cells and the
      Kir4.1 immunolabeling of retinal slices were not different between A(1)AR(-/-)
      and wild-type mice, both in freshly isolated tissues and retinal organ cultures.
      CONCLUSIONS: The data suggest that autocrine activation of A(1) receptors by
      extracellularly generated adenosine mediates the volume homeostasis of Muller
      cells in the murine retina. The swelling-inhibitory effect of triamcinolone is
      mediated by enhancement of endogenous adenosine signaling.

PMID- 19756186
TI  - Idiopathic left ventricular aneurysm causing ventricular tachycardia with 1:1
      ventriculoatrial conduction and intermittent wenckebach block.

PMID- 19756185
TI  - Peroxisome proliferator-activated receptor and retinoic x receptor in alcoholic
      liver disease.
AB  - A growing number of new studies demonstrate that nuclear receptors are involved
      in the development of alcoholic liver disease (ALD). Ethanol metabolism and
      RXR/PPAR functions are tightly interconnected in the liver. Several ethanol
      metabolizing enzymes are potently regulated by RXR and PPARalpha after alcohol
      consumption. The increased ethanol metabolism, in turn, leads to alteration of
      the redox balance of the cells and impairment of RXR/PPAR functions by direct and
      indirect effects of acetaldehyde, resulting in deranged lipid metabolism,
      oxidative stress, and release of proinflammatory cytokines. The use of animal
      models played a crucial role in understanding the molecular mechanisms of ALD. In
      this paper we summarize the reciprocal interactions between ethanol metabolism
      and RXR/PPAR functions. In conclusion, RXR and PPAR play a central role in the
      onset and perpetuation of the mechanisms underling all steps of the clinical
      progression in ALD.

PMID- 19756187
TI  - Physiopathological hypothesis of cellulite.
AB  - A series of questions are asked concerning this condition including as regards to
      its name, the consensus about the histopathological findings, physiological
      hypothesis and treatment of the disease. We established a hypothesis for
      cellulite and confirmed that the clinical response is compatible with this
      hypothesis. Hence this novel approach brings a modern physiological concept with
      physiopathologic basis and clinical proof of the hypothesis. We emphasize that
      the choice of patient, correct diagnosis of cellulite and the technique employed
      are fundamental to success.

PMID- 19756188
TI  - Are you a p-value worshipper?

PMID- 19756189
TI  - Effect of ED-71, a New Active Vitamin D Analog, on Bone Formation in an
      Orthopedically Expanded Suture in Rats. A Histomorphometric Study.
AB  - OBJECTIVES: The aim of this experimental study was to evaluate the effects of ED
      71, a new active vitamin D analog, on bone regeneration in response to expansion
      of the mid-palatal suture, in rats, histomorphometrically. METHODS: Sixteen male
      50-60 days old Wistar rats were separated into two equal groups (control and
      experimental). Both groups were subjected to expansion, and 30 grams of force was
      applied to the maxillary incisors with a helical-spring. Experimental group was
      treated with single-dose ED-71 (0.8 mug/kg body weight) in the mid-palatal suture
      locally and eight control animals received vehicle solution. Bone regeneration in
      the mid-palatal suture was evaluated by bone histomorphometric method and
      mineralized area (Md.Ar), fibrosis area (Fb.Ar), mineralized area/fibrosis area
      (Md.Ar/Fb.Ar), bone area (B.Ar) and osteoblast number (N.Ob) parameters were
      evaluated. Mann Whitney-U test was used for statistical evaluation at P<.05
      level. RESULTS: Statistical analysis showed significant differences between
      groups for all investigated histomorphometric parameters. Md.Ar (P<.001),
      Md.Ar/Fb.Ar (P<.001), B.Ar (P<.01) and N.Ob (P<.001) parameters were
      significantly increased and Fb.Ar (P<.001) measurement was significantly
      decreased in experimental group. ED-71 group with a mean of 24.55+/-6.47 showed
      statistically higher N.Ob than the control group (mean N.Ob: 12.82+/-5.81).
      CONCLUSIONS: ED-71 has positive effects on early phase of bone regeneration in
      the mid-palatal suture in response to expansion and may be beneficial in routine
      maxillary expansion procedures.

PMID- 19756190
TI  - Effects of fluorosis and self etching primers on shear bond strengths of
      orthodontic brackets.
AB  - OBJECTIVES: To evaluate the effects fluorosis and self etching primers (SEP) on
      shear bond strengths (SBS) of orthodontic brackets. METHODS: A total of 48 (24
      fluorosed and 24 non-fluorosed) non-carious freshly extracted human permanent
      premolar teeth were used in this study. Fluorosed teeth were selected according
      to the modified Thylstrup and Fejerskov index (TFI), which is based on the
      clinical changes in fluorosed teeth. Fluorosed and non-fluorosed teeth were
      randomly assigned to 4 groups of 12 each. In groups I (non-fluorosed teeth) and
      II (fluorosed teeth), standard etching protocol was used and brackets were bonded
      with Light Bond. In groups III (non-fluorosed teeth) and IV (fluorosed teeth),
      Transbond Plus SEP was used and brackets were bonded with Transbond XT Light Cure
      Adhesive. All specimens were cured with a halogen light. After bonding, SBS of
      the brackets were tested with Universal testing machine. After debonding, all
      teeth and brackets in the test groups were examined under 10x magnifications. Any
      adhesive remained after debonding was assessed and scored according to the
      modified Adhesive Remnant Index (ARI). RESULTS: ANOVA indicated a significant
      difference between groups (P<.001). SBS in group II (Light Bond+Fluorosis) were
      significantly lower than other groups. ARI scores of the groups were also
      significantly different (P<.001). There was a greater frequency of ARI scores of
      1,2 and 3 in group II (Light Bond+Fluorosis). CONCLUSIONS: When standard etching
      protocol was used enamel fluorosis significantly decreased the bond strength of
      orthodontic brackets. Satisfactory bond strengths were obtained when SEP was used
      for bonding brackets to the fluorosed teeth.

PMID- 19756191
TI  - Effect of multiple consecutive adhesive coatings on microleakage of class v
      cavities.
AB  - OBJECTIVES: The purpose of this in vitro study was to evaluate the effect of
      multiple consecutive adhesive coatings of a one-step self-etch adhesive on
      microleakage of Class V cavities. METHODS: Standardized box shaped Class V
      cavities were prepared onto the buccal side of forty five non-carious human
      premolar teeth. The teeth were randomly divided into three groups of fifteen
      teeth in each and restored as: Group I- one-step self-etch adhesive resin
      (Clearfil S3, Kuraray Co. Ltd., Osaka, Japan) was applied according to the
      manufacturer's instructions, Group II- two consecutive same one-step self-etch
      adhesive application was performed, and Group III- three consecutive same one
      step self-etch adhesive application was performed. After the adhesive
      applications light curing unit was activated for 20 seconds and the cavities were
      restored with a composite resin. The restorations were finished with aluminum
      oxide discs and the specimens were stored in water at room temperature for 24
      hours before they were immersed in 2% methylene blue for 48 hours. The dye
      penetration was examined under a stereomicroscope and the asymtotic significance
      were analysed with Kruskall Wallis and Mann Whitney U tests and dentin-enamel
      margins were compared with each other with Wilcoxon Signed Rank test. RESULTS:
      The microleakage at the dentinal margins of Class V cavities were significantly
      decreased with two (Group II) and three (Group III) consecutive adhesive
      applications (P<.05). There was no significant difference between Group I, Group
      II and Group III at the enamel margins (P<.05). The microleakage at the dentinal
      margins were significantly higher than the enamel margins in Group I and Group II
      but in Group III there was no statistically significant difference (P<.05).
      CONCLUSIONS: Within the limitations of this in vitro study, it may be concluded
      that three consecutive applications of the one-step self-etch adhesive resin
      provided better sealing than the one coat of adhesive resin at the dentinal
      margins of Class V cavities.

PMID- 19756192
TI  - Articulation performance of patients wearing obturators with different buccal
      extension designs.
AB  - OBJECTIVES: The primary goal of prosthetic obturation is closure of the
      maxillectomy defect and separation of the oral cavity from the sinonasal cavities
      by use of different bulb designs. The aim of this study was to evaluate the
      articulation performance of obturator patients with three different buccal
      extension designs. METHODS: Five patients with palatal defects of comparable
      sizes at ages ranging from 42 to 74 were evaluated. Starting at postoperative 4
      months, speech intelligibility (SI) was assessed without a prosthetic obturator
      and with an obturator of buccal extensions 15 mm (high), 10 mm (medium) and 5 mm
      (low), respectively. Assessments were performed at four week intervals for
      adaptation. The articulation performance of patients with different buccal
      extension designs were evaluated on speech intelligibility. The data tested using
      Friedman test. RESULTS: The mean SI score without an obturator was 45.04%+/
      5.86%. SI was found to be significantly increased with obturators of any buccal
      extensions with the mean values 90.50%, %94.24% and 91.20% for high, medium, and
      low buccal extensions respectively. When the SI score was compared between three
      buccal extension types medium was found to be significantly higher compared to
      others (P<.05). CONCLUSIONS: Obturators improve speech intelligibility
      irrespective of their buccal extension levels. Nevertheless, medium size buccal
      extension enables the optimum sealing for better articulation.

PMID- 19756193
TI  - Circulating beta(1) Adrenergic Autoantibodies from Patients with Chronic
      Periodontitis Interact with Gingival Fibroblasts.
AB  - OBJECTIVES: To demonstrate the presence of circulating autoantibodies (Abs) from
      patients with chronic periodontitis (CP) that interacted with human gingival
      fibroblast membranes activating beta(1) adrenoceptors (beta(1)-AR). METHODS: Sera
      and purified IgG from 25 patients with CP and 20 age-matched healthy subjects
      were studied by flow cytometry, ELISA and DNA synthesis. Human gingival
      fibroblast membranes and/or synthetic peptides with amino acid sequences
      identical to human beta(1)-AR were used as antigens. RESULTS: By flow cytometry
      and ELISA procedures, we proved that the serum-purified IgG fraction from
      patients with CP reacted with the fibroblast surface and to the beta(1) synthetic
      peptide. The corresponding affinity-purified anti-beta(1) peptide Abs displayed
      agonist-like activity associated with specific receptor activation, inhibiting
      the DNA synthesis of human gingival fibroblasts. CONCLUSIONS: This study
      demonstrates that beta(1)-AR autoantibodies are elevated in patients with CP.
      These autoantibodies were targeted to the fibroblasts, and specifically to the
      beta(1)-AR, and has receptor-like activity inhibiting DNA synthesis.

PMID- 19756194
TI  - Effect of Thermo-mechanical Load Cycling on Microleakage in Class II Ormocer
      Restorations.
AB  - OBJECTIVES: The objective of this in vitro study was to evaluate the marginal
      sealing ability of an ormocer in comparison with a hybrid composite when using
      thermocycling and load cycling procedures together in the study design. METHODS:
      Modified proximal Class II cavities were prepared on the mesial and distal
      surfaces of twenty-two human premolars. Each tooth was restored with Admira and
      contralaterally with TPH Spectrum. Half of all of the teeth were subjected to
      thermo-mechanical load cycling. After dye penetration, longitudinal sections in
      mesio-distal direction were prepared and examined under a stereomicroscope. Data
      were analyzed with Mann Whitney U test. RESULTS: The results showed that the
      thermo-mechanical load cycling caused a statistically significant increase in
      gingival microleakage when compared with the non-thermocycled and non-loaded
      restorations for both the materials Admira (P=0.006) and TPH Spectrum (P=0.023).
      CONCLUSIONS: Simultaneous load cycling and thermocycling are decisive factors in
      the in vitro assessment of gingival microleakage, which still remains to be a
      clinical problem even with the ormocer system Admira.

PMID- 19756195
TI  - Clinical characteristics of patients with trigeminal neuralgia referred to
      neurosurgery.
AB  - OBJECTIVES: To investigate the clinical characteristics of patients with
      trigeminal neuralgia referred to surgery in a center of reference. METHODS: We
      evaluated the general characteristics of 395 patients with trigeminal neuralgia
      referred to neurosurgery as treatment. They corresponded to 2 samples of 1984 and
      2004. The EDOF-HC protocol (Orofacial Pain Questionnaire) and the medical profile
      were used. RESULTS: In the first study (1984), with 290 patients, the higher
      prevalence was: women (57.3%), white (95.5%), with mean age of 62.5. The most
      affected trigeminal branches were the maxillary and/or mandibular branches
      (65.5%), and the right side was the most affected (57.6%). From the second study
      (2004), with 105 patients, 57.1% were women, 75.2% white, with a mean age of
      60.8. The maxillary and/or mandibular branches (79.0%) and the right side (69.5%)
      were the most affected. Both samples had neurological abnormalities and systemic
      diseases (mainly cardiovascular). CONCLUSIONS: General characteristics of these
      patients were similar to other samples of trigeminal neuralgia. Neurological
      findings were also present in patients with no previous surgical treatment for
      TN. Hypertension and cardiac diseases were also frequent and make the monitoring
      of the patients during crises necessary.

PMID- 19756196
TI  - Cuspal movement related to different bonding techniques using etch-and-rinse and
      self-etch adhesive systems.
AB  - OBJECTIVES: To investigate the effects of adhesion technique using different
      contemporary adhesive systems on the cuspal movement in class II composite
      restorations in human premolar teeth. METHODS: Human premolar teeth were prepared
      with class II cavities and then restored with composite and etch-and-rinse (Adper
      Scotchbond Multi Purpose and Adper Single Bond) or self-etch (Clearfil SE Bond
      and Clearfil S3 Bond) adhesive systems under different bonding techniques (total
      bonding and selective bonding). The influence of an intermediate layer of
      flowable composite was also evaluated. The cuspal distance was measured before
      and after the restorative procedure, and the difference was recorded as cuspal
      movement. The data were submitted to ANOVA test and Tukey's post hoc comparison
      procedure test (alpha=0.05). RESULTS: For all adhesive systems, the teeth
      restored with selective bonding technique showed lower values of cuspal movement
      and the use of an intermediary layer of flowable composite did not show any
      influence on the cuspal movement. CONCLUSIONS: Both the adhesive techniques
      tested were not able to prevent the cuspal movement. However, selectively bonded
      class II composite restorations demonstrated lower values of cuspal movement
      comparing with total bonding technique, and the use of an intermediate layer of
      flowable composite did not diminish the values of cuspal movement.

PMID- 19756197
TI  - Double inverted mesiodentes: report of an unusual case.
AB  - This report presents an extremely rare occurrence of two inverted mesiodentes in
      a child patient. Extraction of both mesiodentes was indicated, owing to the axial
      rotation of the permanent central incisors caused by these impacted supernumerary
      teeth. Radiographic evidence of complete healing was observed 24 months following
      surgical removal of the inverted mesiodentes.

PMID- 19756198
TI  - Extensive ameloblastic fibroma in an adolescent patient: a case report with a
      follow-up of 4 years.
AB  - Ameloblastic fibroma (AF) is a rare odontogenic tumour of the jaw which usually
      occurs in the first 2 decades of life. The common clinical manifestation is a
      slow-growing swelling. We report a case of a 16-year-old male patient presenting
      with extensive AF of the mandible. He underwent a conservative enucleation. The
      tumour recurred 2 years after the initial surgery, requiring the second
      enucleation. The patient has continued to be followed closely and has been
      disease-free for 4 years. Recent evidence suggests that the recurrent rate of AF
      is relatively high, and malignant transformation of AF may occur after
      recurrences or multiple surgeries. A conservative treatment approach with close
      surveillance is recommended. Anatomical limitations should be taken into account,
      especially when enucleation of AF in the posterior portion of the jaw is
      performed. Current surgical pathologic issues of the tumour are also discussed.

PMID- 19756199
TI  - Vital Bleaching of Tetracycline-Stained Teeth by Using KTP Laser: A Case Report.
AB  - Bleaching of discolored teeth is one of the most important topics in aesthetic
      dentistry. A great challenge in this area is obtaining good results in
      tetracycline-stained teeth. The wavelength and features of KTP laser, which is a
      type of Nd:YAG laser, seem to be appropriate for bleaching of these teeth. This
      case report underlines the importance of knowledge about the photochemical
      bleaching by using the KTP laser and its side effects on soft tissues.

PMID- 19756200
TI  - Unusual synchronous presentation of maxillary sinus fibrosarcoma and gemistocytic
      astrocytoma with a complication called leukocytoclastic vasculitis: a case
      report.
AB  - Fibrosarcoma of the paranasal sinuses is extremely rare pathology and there is
      limited report in the literature. We report synchronous presentation of maxillary
      sinus fibrosarcoma and gemistocytic astrocytoma which is, to our knowledge,
      unique in the literature. Both tumors metastases to other organ rarely and the
      metastatic spread of gemistocytic astrocytoma to fibrosarcoma or vice versa have
      also not been reported in the literature yet. This report discusses the clinical
      course of the disease, outcome of the treatment approach and survival as well as
      an unusual occurrence of leukocytoclastic vasculitis during the course of
      radiotherapy in such unusual presentation.

PMID- 19756201
TI  - "Opening" the mesenchymal stem cell tool box.
AB  - Adult mesenchymal stem cells (MSCs) are adherent stromal cells able to self-renew
      and differentiate into a wide variety of cells and tissues. MSCs can be obtained
      from distinct tissue sources and have turned out to be successfully manipulated
      in vitro. As adult stem cells, MSCs are less tumorigenic than their embryonic
      correlatives and posses another unique characteristic which is their almost null
      immunogenicity. Moreover, these cells seem to be immunosuppressive in vitro.
      These facts together with others became MSCs a promising subject of study for
      future approaches in bioengineering and cell-based therapy. On the other hand,
      new strategies to achieve long-term integration as well as efficient
      differentiation of these cells at the area of the lesion are still challenging,
      and the signalling pathways ruling these processes are not completely well
      characterized. In this review, we are going summarize the general landscape and
      current status of the MSC tool as well as their wide potential in tissue
      engineering, from neuronal to tooth replacement. Highlights and pitfalls for
      further clinical applications will be discussed.

PMID- 19756202
TI  - Effects of airway problems on maxillary growth: a review.
AB  - The volume of air passing through the nose and nasopharinx is limited by its
      shape and diameter. Continuous airflow through the nasal passage during breathing
      induces a constant stimulus for the lateral growth of maxilla and for lowering of
      the palatal vault. Maxillary morphological differences exist between patients
      with airway problems and control groups, identifying a potential etiological role
      in these patients. The purpose of this article was to review the literature on
      the interaction between airway problems and expressed maxillary morphology
      including specific dental and skeletal malocclusions. Statistically significant
      differences were found between patients with airway problems and control groups,
      in maxillary skeletal morphology including shorter maxillary length, more
      proclined maxillary incisors, thicker and longer soft palate, narrower maxillary
      arch and higher palatal vault.

PMID- 19756203
TI  - CELL SEGMENTATION USING HESSIAN-BASED DETECTION AND CONTOUR EVOLUTION WITH
      DIRECTIONAL DERIVATIVES.
AB  - The large amount of data produced by biological live cell imaging studies of cell
      behavior requires accurate automated cell segmentation algorithms for rapid,
      unbiased and reproducible scientific analysis. This paper presents a new approach
      to obtain precise boundaries of cells with complex shapes using ridge measures
      for initial detection and a modified geodesic active contour for curve evolution
      that exploits the halo effect present in phase-contrast microscopy. The level set
      contour evolution is controlled by a novel spatially adaptive stopping function
      based on the intensity profile perpendicular to the evolving front. The proposed
      approach is tested on human cancer cell images from LSDCAS and achieves high
      accuracy even in complex environments.

PMID- 19756204
TI  - Highly-parallel metabolomics approaches using LC-MS for pharmaceutical and
      environmental analysis.
AB  - The 'omics' approaches - genomics, proteomics and metabolomics - are based on
      high-throughput, high-information-content analysis. Using these approaches, as
      opposed to targeting one or a few analytes, a holistic understanding of the
      composition of a sample can be obtained. These approaches have revolutionized
      sample-analysis and data-processing protocols. In metabolomic studies, hundreds
      of small molecules are simultaneously analyzed using analytical platforms (e.g.,
      gas chromatography-mass spectrometry (GC-MS) or liquid chromatography coupled to
      tandem mass spectrometry (LC-MS(2))). This philosophy of holistic analysis and
      the application of high-throughput, high-information-content analysis offer
      several advantages. In this article, we compare the conventional analytical
      approach of one or a few analytes per sample to the LC-MS(2)-based metabolomics
      type approach in the context of pharmaceutical and environmental analysis.

PMID- 19756205
TI  - Major League Baseball Players' Life Expectancies.
AB  - OBJECTIVE: We examine the importance of anthropometric and performance measures,
      and age, period, and cohort effects in explaining life expectancies among major
      league baseball (MLB) players over the past century. METHODS: We use discrete
      time hazard models to calculate life tables with covariates with data from Total
      Baseball, a rich source of information on all players who played in the major
      league. RESULTS: Compared to 20-year-old U.S. males, MLB players can expect
      almost five additional years of life. Height, weight, handedness, and player
      ratings are unassociated with the risk of death in this population of highly
      active and successful adults. Career length is inversely associated with the risk
      of death, likely because those who play longer gain additional incomes, physical
      fitness, and training. CONCLUSIONS: Our results indicate improvements in life
      expectancies with time for all age groups and indicate possible improvements in
      longevity in the general U.S. population.

PMID- 19756206
TI  - Retrograde ethanol infusion in the vein of Marshall: regional left atrial
      ablation, vagal denervation and feasibility in humans.
AB  - BACKGROUND: The vein of Marshall (VOM) is an attractive target during ablation of
      atrial fibrillation due to its autonomic innervation, its location anterior to
      the left pulmonary veins and drainage in the coronary sinus. METHODS AND RESULTS:
      We studied 17 dogs. A coronary sinus venogram showed a VOM in 13, which was
      successfully cannulated with an angioplasty wire and balloon. In 5 dogs,
      electroanatomical maps of the left atrium were performed at baseline and after
      ethanol infusion in the VOM, which demonstrated a new crescent-shaped scar,
      extending from the annular left atrium towards the posterior wall and left
      pulmonary veins. In 4 other dogs, effective refractory periods (ERP) were
      measured at 3 sites in the left atrium, before and after high-frequency bilateral
      vagal stimulation. The ERP decreased from 113.6+/-35.0 ms to 82.2+/-25.4 ms
      (p<0.05) after vagal stimulation. After VOM ethanol infusion, vagally-mediated
      ERP decrease was eliminated (from 108.6+/-24.1 ms to 96.4 +/-16.9ms, p=NS). The
      abolition of vagal effects was limited to sites near the VOM (ERP: 104+/-14 ms,
      vs 98.6+/-12.2 ms post vagal stimulation, p=ns), as opposed to sites remote to
      VOM (ERP: 107.2+/-14.9 ms, vs 78.6+/-14.7ms post vagal stimulation, p<0.05). To
      test feasibility in humans, 5 patients undergoing pulmonary vein antral isolation
      had successful VOM cannulation and ethanol infusion: left atrial voltage maps
      demonstrated new scar involving the infero-posterior left atrial wall extending
      towards the left pulmonary veins. CONCLUSIONS: Ethanol infusion in then VOM
      achieves significant left atrial tissue ablation, abolishes local vagal responses
      and is feasible in humans.

PMID- 19756207
TI  - Implications of Ethnic Identity Exploration and Ethnic Identity Affirmation and
      Belonging for Intergroup Attitudes Among Adolescents.
AB  - The present paper develops and tests two temporal models of the relationships
      among adolescents' ethnic identity exploration, ethnic identity affirmation and
      belonging, and attitudes toward their racial/ethnic ingroup and outgroups.
      Structural equation models for Euro-Americans, Asian Americans, and Latinos
      revealed that all hypothesized relationships were positive and significant. The
      model in which ethnic identity exploration (at Time 1) predicts ethnic identity
      affirmation and belonging (at Time 2) was superior to the alternative model in
      which the relationship between them was reversed (i.e., affirmation and belonging
      at Time 1 predicts exploration at Time 2). Results (1) support the importance of
      exploration as a basis for establishing a secure attachment to one's ethnic
      identity, which, in turn, has positive implications for attitudes toward one's
      own group and other groups and (2) suggest that maintenance of ethnic identity is
      compatible with positive attitudes toward ethnic outgroups.

PMID- 19756208
TI  - The Origins of Diverse Domains of Mathematics: Generalist Genes but Specialist
      Environments.
AB  - The authors assessed 2,502 ten-year-old children, members of 1,251 pairs of
      twins, on a Web-based battery of problems from 5 diverse aspects of mathematics
      assessed as part of the U.K. national curriculum. This 1st genetic study into the
      etiology of variation in different domains of mathematics showed that the
      heritability estimates were moderate and highly similar across domains and that
      these genetic influences were mostly general. Environmental factors unique to
      each twin in a family (rather than shared by the 2 twins) explained most of the
      remaining variance, and these factors were mostly specific to each domain.

PMID- 19756209
TI  - Gender, Anxiety, and Depressive Symptoms: A Longitudinal Study of Early
      Adolescents.
AB  - Does anxiety lead to depression more for girls than for boys? This study
      prospectively examines gender differences in the relationship between anxiety and
      depressive symptoms in early adolescence. One hundred thirteen 11- to 14-year-old
      middle school students complete questionnaires assessing depressive symptoms and
      three dimensions of anxiety (worry and oversensitivity, social concerns and
      concentration, and physiological anxiety) as well as total anxiety symptoms at an
      initial assessment and 1 year later. Total anxiety and worry and oversensitivity
      symptoms are found to predict later depressive symptoms more strongly for girls
      than for boys. There is a similar pattern of results for social concerns and
      concentration symptoms, although this does not reach statistical significance.
      Physiological anxiety predicts later depressive symptoms for both boys and girls.
      These findings highlight the importance of anxiety for the development of
      depression in adolescence, particularly worry and oversensitivity among girls.

PMID- 19756210
TI  - Linear quadratic gaussian-based closed-loop control of type 1 diabetes.
AB  - BACKGROUND: We investigated the applicability of linear quadratic Gaussian (LQG)
      methodology to the subcutaneous blood glucose regulation problem. We designed an
      LQG-based feedback control algorithm using linearization of a previously
      published metabolic model of type 1 diabetes. A key feature of the controller is
      a Kalman filter used to estimate metabolic states of the patient based on
      continuous glucose monitoring. Insulin infusion is computed from linear quadratic
      regulator feedback gains applied to these estimates, generally seeking to
      minimize squared deviations from a target glucose concentration and basal insulin
      rate. We evaluated in silico subject-specific LQG control and compared it to
      preexisting proportional-integral-derivative control.

PMID- 19756211
TI  - Missing Data in Longitudinal Clinical Trials Part A: Design and Conceptual
      Issues.

PMID- 19756212
TI  - Sample Size Determination for Studies with Repeated Continuous Outcomes.

PMID- 19756213
TI  - Cryo-Imaging of Fluorescently-Labeled Single Cells in a Mouse.
AB  - We developed a cryo-imaging system to provide single-cell detection of
      fluorescently labeled cells in mouse, with particular applicability to stem cells
      and metastatic cancer. The Case cryo-imaging system consists of a fluorescence
      microscope, robotic imaging positioner, customized cryostat, PC-based control
      system, and visualization/analysis software. The system alternates between
      sectioning (10-40 MUm) and imaging, collecting color brightfield and fluorescent
      block-face image volumes >60GB. In mouse experiments, we imaged quantum-dot
      labeled stem cells, GFP-labeled cancer and stem cells, and cell-size fluorescent
      microspheres. To remove subsurface fluorescence, we used a simplified model of
      light-tissue interaction whereby the next image was scaled, blurred, and
      subtracted from the current image. We estimated scaling and blurring parameters
      by minimizing entropy of subtracted images. Tissue specific attenuation
      parameters were found [u(T) : heart (267 +/- 47.6 MUm), liver (218 +/- 27.1 MUm),
      brain (161 +/- 27.4 MUm)] to be within the range of estimates in the literature.
      "Next image" processing removed subsurface fluorescence equally well across
      multiple tissues (brain, kidney, liver, adipose tissue, etc.), and analysis of
      200 microsphere images in the brain gave 97+/-2% reduction of subsurface
      fluorescence. Fluorescent signals were determined to arise from single cells
      based upon geometric and integrated intensity measurements. Next image processing
      greatly improved axial resolution, enabled high quality 3D volume renderings, and
      improved enumeration of single cells with connected component analysis by up to
      24%. Analysis of image volumes identified metastatic cancer sites, found homing
      of stem cells to injury sites, and showed microsphere distribution correlated
      with blood flow patterns.We developed and evaluated cryo-imaging to provide
      single-cell detection of fluorescently labeled cells in mouse. Our cryo-imaging
      system provides extreme (>60GB), micron-scale, fluorescence, and bright field
      image data. Here we describe our image pre-processing, analysis, and
      visualization techniques. Processing improves axial resolution, reduces
      subsurface fluorescence by 97%, and enables single cell detection and counting.
      High quality 3D volume renderings enable us to evaluate cell distribution
      patterns. Applications include the myriad of biomedical experiments using
      fluorescent reporter gene and exogenous fluorophore labeling of cells in
      applications such as stem cell regenerative medicine, cancer, tissue engineering,
      etc.

PMID- 19756214
TI  - Youth After-School Programs: Time to Involve the Parents and Community?

PMID- 19756215
TI  - Whole Mouse Cryo-Imaging.
AB  - The Case cryo-imaging system is a section and image system which allows one to
      acquire micron-scale, information rich, whole mouse color bright field and
      molecular fluorescence images of an entire mouse. Cryo-imaging is used in a
      variety of applications, including mouse and embryo anatomical phenotyping, drug
      delivery, imaging agents, metastastic cancer, stem cells, and very high
      resolution vascular imaging, among many. Cryo-imaging fills the gap between whole
      animal in vivo imaging and histology, allowing one to image a mouse along the
      continuum from the mouse -> organ -> tissue structure -> cell -> sub-cellular
      domains. In this overview, we describe the technology and a variety of exciting
      applications. Enhancements to the system now enable tiled acquisition of high
      resolution images to cover an entire mouse. High resolution fluorescence imaging,
      aided by a novel subtraction processing algorithm to remove sub-surface
      fluorescence, makes it possible to detect fluorescently-labeled single cells.
      Multi-modality experiments in Magnetic Resonance Imaging and Cryo-imaging of a
      whole mouse demonstrate superior resolution of cryo-images and efficiency of
      registration techniques. The 3D results demonstrate the novel true-color volume
      visualization tools we have developed and the inherent advantage of cryo-imaging
      in providing unlimited depth of field and spatial resolution. The recent results
      continue to demonstrate the value cryo-imaging provides in the field of small
      animal imaging research.

PMID- 19756216
TI  - Socioeconomic context and the association between marriage and Mexico-U.S.
      migration.
AB  - In this paper, I analyze how the association between Mexico-U.S. migration and
      marriage varies across socioeconomic settings in origins. Using Mexican Migration
      Project data and employing bilevel survival analysis with controls for
      socioeconomic, migrant network, and marriage market characteristics and family
      size, I find that single people are most likely to migrate relative to those
      married in areas of recent industrialization, where the Mexican patriarchal
      system is weaker and economic opportunities for both men and women make post
      marital migration less attractive. Marital status is not significant in
      agriculture-dependent areas, where the bargaining power of husbands might be
      higher relative to other settings; their age-profiles of earnings flatter; and
      remunerated female work scarcer, making migration attractive later in the life
      course.

PMID- 19756217
TI  - Modeling of Calibration Effectiveness and Blood-to-Interstitial Glucose Dynamics
      as Potential Confounders of the Accuracy of Continuous Glucose Sensors during
      Hyperinsulinemic Clamp.
AB  - BACKGROUND: Models of the dynamics of interstitial fluid-based continuous glucose
      sensors imply a variable sensor deviation from reference blood glucose (BG),
      depending on both sensor calibration procedure and BG dynamics. These effects
      could have a significant effect on the cross-interpretation of nonidentical
      accuracy studies. METHODS: Hyperinsulinemic euglycemic and hypoglycemic clamps
      were performed on 39 subjects with type 1 diabetes wearing the Medtronic
      Continuous Glucose Monitoring System(r). Sensor calibration and interstitial
      glucose (IG) dynamics were modeled and analyzed as potential confounders of
      sensor deviation from reference BG. RESULTS: The mean absolute deviation (MAD) of
      sensor data was 20.9 mg/dl during euglycemia and 24.5 mg/dl during descent into
      and recovery from hypoglycemia. Computer-generated recalibration reduced MAD to
      10.6 and 14.6 mg/dl, respectively. Modeling of IG dynamics reduced the MAD
      further to 10.0 and 10.4 mg/dl (using idiosyncratic parameters) or to 10.6 and
      11.5 mg/dl (using model parameters common for all subjects), respectively.
      CONCLUSIONS: The sensor MAD from reference is strongly influenced by the choice
      of calibration points. Thus, cross-experiment comparisons of sensor accuracy are
      likely to be heavily dependent on the employed calibration procedures. Demanding
      calibration points substantially differing in value was found to improve
      calibration effectiveness. Simulation using existing IG models and population
      parameters reduced the bias resulting from BG-IG dynamics.

PMID- 19756218
TI  - Temperament Measures of African-American Infants: Change and Convergence with
      Age.
AB  - Studies of infant temperament are inconsistent with regard to convergence across
      measurement sources. In addition, little published work is available that
      describes temperament in minority infants. In this study, measures of temperament
      at 3- and 6-months were made for 24 African-American infants. Although maternal
      ratings of activity and fussiness did not correlate with more objective measures
      at 3-months of age, ratings and the more objective assessments were significantly
      correlated at 6-months.

PMID- 19756219
TI  - Personality Trait Change in Adulthood.
AB  - Recent longitudinal and cross-sectional aging research has shown that personality
      traits continue to change in adulthood. In this article, we review the evidence
      for mean-level change in personality traits, as well as for individual
      differences in change across the life span. In terms of mean-level change, people
      show increased selfconfidence, warmth, self-control, and emotional stability with
      age. These changes predominate in young adulthood (age 20-40). Moreover, mean
      level change in personality traits occurs in middle and old age, showing that
      personality traits can change at any age. In terms of individual differences in
      personality change, people demonstrate unique patterns of development at all
      stages of the life course, and these patterns appear to be the result of specific
      life experiences that pertain to a person's stage of life.

PMID- 19756221
TI  - Neuroimaging of Nicotine Dependence: Key Findings and Application to the Study of
      Smoking-Mental Illness Comorbidity.
AB  - Modern neuroimaging techniques offer the opportunity to non-invasively study
      neuroanatomical and neurofunctional correlates of nicotine dependence and its
      treatment. In the present review, the most widely used neuroimaging techniques
      magnetic resonance imaging (MRI), positron emission tomography (PET) and
      functional MRI (fMRI)-are briefly described and their strengths and limitations
      discussed. The use of these techniques has resulted in new insights into the
      neuropharmacology of tobacco addiction. Studies comparing smokers and nonsmokers
      have shown that smokers have less grey matter density in frontal brain regions
      and greater concentrations of nicotinic receptors. Research on the effects of
      smoking a cigarette confirms that smoking leads to the release of dopamine in
      brain reward areas and to nicotinic receptor binding. Studies of smoking
      abstinence have identified functional brain correlates of increased reactivity to
      smoking-related cues, and worsening of concentration. To date, neuroimaging
      studies of nicotine dependence among individuals with mental illness have focused
      almost exclusively on schizophrenia. A conceptual/methodological framework for
      studying dual diagnosis using neuroimaging measures is provided with the aim of
      spurring additional research in this area.

PMID- 19756222
TI  - Feature Selection of 3D Volume Data through Multi-Dimensional Transfer Functions.
AB  - Direct volume rendering maps data values to visual properties such as
      transparency and color through transfer functions. Traditional multi-dimensional
      functions are generated based on a 2D histogram of function value and gradient
      magnitude. When two different features overlap in the 2D histogram, the
      traditional transfer functions cannot visually distinguish the features, since
      overlapped areas have similar visual properties. In this paper, we describe a new
      multi-dimensional transfer function that enables visual differentiation of
      features even in the case when two different features overlap in the 2D
      histogram. Furthermore, we provide details of an implementation of our transfer
      function on modern programmable graphics hardware.

PMID- 19756223
TI  - The Complex World of Adolescent Literacy: Myths, Motivations, and Mysteries.
AB  - In this article, Elizabeth Birr Moje, Melanie Overby, Nicole Tysvaer, and Karen
      Morris challenge some of the prevailing myths about adolescents and their choices
      related to reading. The reading practices of youth from one urban community are
      examined using mixed methods in an effort to define what, how often, and why
      adolescents choose to read. By focusing on what features of texts youth find
      motivating, the authors find that reading and writing frequently occur in a range
      of literacy contexts outside school. However, only reading novels on a regular
      basis outside of school is shown to have a positive relationship to academic
      achievement as measured by school grades. This article describes how adolescents
      read texts that are embedded in social networks, allowing them to build social
      capital. Conclusions are framed in terms of the mysteries that remain - namely,
      how to build on what motivates adolescents' literacy practices in order to both
      promote the building of their social selves and improve their academic outcomes.

PMID- 19756224
TI  - Microwave assisted tandem reactions for the synthesis of 2-hydrazolyl-4
      thiazolidinones.
AB  - A tandem method for the synthesis of 2-hydrazolyl-4-thiazolidinones (5) from
      commercially available materials in a 3 component reaction has been developed.
      The reaction connects aldehydes, thiosemicarbazides and maleic anhydride,
      effectively assisted by microwave irradiation. The synthesis of a new type of
      compound, 2-hydrazolyl-5,5-diphenyl-4-thiazolidinone (7), obtained by treatment
      of thiosemicarbazone with benzil in basic media is also reported. HOMO/LUMO
      energies, orbital coefficients and charge distribution were used to explain the
      proposed reaction mechanism.

PMID- 19756225
TI  - Couples' Reasons for Cohabitation: Associations with Individual Well-Being and
      Relationship Quality.
AB  - This study used a new measure to examine how different types of reasons for
      cohabitation were associated with individual well-being and relationship quality
      in a sample of 120 cohabiting heterosexual couples (N = 240). Spending more time
      together and convenience were the most strongly endorsed reasons. The degree to
      which individuals reported cohabiting to test their relationships was associated
      with more negative couple communication and more physical aggression as well as
      lower relationship adjustment, confidence, and dedication. Testing the
      relationship was also associated with higher levels of attachment insecurity and
      more symptoms of depression and anxiety. Men were more likely than women to
      endorse testing their relationships and less likely to endorse convenience as a
      reason for cohabiting.

PMID- 19756226
TI  - Longitudinal Relationships Between Family Functioning and Identity Development in
      Hispanic Adolescents: Continuity and Change.
AB  - The present study was designed to investigate trajectories of identity
      development and their relationship to family functioning in a sample of Hispanic
      adolescents and their primary caregivers. Two hundred fifty adolescents completed
      measures of identity coherence and confusion and of family functioning, and
      parents completed measures of family functioning. Significant variability over
      time and across individuals emerged in identity confusion, but not in identity
      coherence. As a result, the present analyses focused on identity confusion.
      Changes in adolescent-reported, but not parent-reported, family functioning were
      significantly related to changes in identity confusion. Follow-up analyses
      suggested that family functioning primarily influences identity confusion in
      early adolescence, but that identity confusion begins to exert a reciprocal
      effect in middle adolescence. Exploratory latent growth mixture modeling (LGMM)
      analyses produced three classes of adolescents based on their baseline values and
      change trajectories in identity confusion. The potential for family-strengthening
      interventions to affect identity development is discussed.

PMID- 19756227
TI  - Lexical retrieval and semantic knowledge in patients with left inferior temporal
      lobe lesions.
AB  - BACKGROUND: It has been proposed that anomia following left inferior temporal
      lobe lesions may have two different underlying mechanisms with distinct neural
      substrates. Specifically, naming impairment following damage to more posterior
      regions (BA 37) has been considered to result from a disconnection between
      preserved semantic knowledge and phonological word forms (pure anomia), whereas
      anomia following damage to anterior temporal regions (BAs 38, 20/21) has been
      attributed to the degradation of semantic representations (semantic anomia).
      However, the integrity of semantic knowledge in patients with pure anomia has not
      been demonstrated convincingly, nor were lesions in these cases necessarily
      confined to BA 37. Furthermore, evidence of semantic anomia often comes from
      individuals with bilateral temporal lobe damage, so it is unclear whether
      unilateral temporal lobe lesions are sufficient to produce significant semantic
      impairment. AIMS: The main goals of this study were to determine whether anomia
      following unilateral left inferior temporal lobe damage reflected a loss of
      semantic knowledge or a post-semantic deficit in lexical retrieval and to
      identify the neuroanatomical correlates of the naming impairment. METHODS
      #ENTITYSTARTX00026; PROCEDURES: Eight individuals who underwent left anterior
      temporal lobectomy (L ATL) and eight individuals who sustained left posterior
      cerebral artery strokes (L PCA) completed a battery of language measures that
      assessed lexical retrieval and semantic processing, and 16 age- and education
      matched controls also completed this battery. High-resolution structural brain
      scans were collected to conduct lesion analyses. OUTCOMES #ENTITYSTARTX00026;
      RESULTS: Performance of L ATL and L PCA patients was strikingly similar, with
      both groups demonstrating naming performance ranging from moderately impaired to
      unimpaired. Anomia in both groups occurred in the context of mild deficits to
      semantic knowledge, which manifested primarily as greater difficulty in naming
      living things than nonliving things and greater difficulty in processing
      visual/perceptual as opposed to functional/associative semantic attributes.
      Lesion analyses indicated that both patient groups sustained damage to anterior
      inferior temporal lobe regions implicated in semantic processing. CONCLUSIONS:
      These results contribute to a better understanding of the cognitive mechanism of
      naming impairment in patients with temporal lobe damage and support the notion
      that pure anomia and semantic anomia represent two endpoints along a continuum of
      semantic impairment. Unilateral left temporal lobe lesions in our patients
      resulted in relatively mild semantic deficits that were apparent primarily in
      lexical production tasks, whereas severe semantic impairment likely requires
      bilateral temporal lobe damage.

PMID- 19756228
TI  - Auditory Oddball fMRI in Schizophrenia: Association of Negative Symptoms with
      Regional Hypoactivation to Novel Distractors.
AB  - Schizophrenia is associated with abnormal processing of salient stimuli, which
      may contribute to clinical symptoms. We used fMRI and a standard auditory 3
      stimulus task to examine attention processing. Target stimuli and novel
      distractors were presented to 17 patients and 21 healthy controls and activation
      was correlated with negative and positive symptoms. To targets, patients
      overactivated multiple regions including premotor cortex, anterior cingulate,
      temporal cortex, insula, and hippocampus, and also showed attenuated deactivation
      within occipital cortex. To distractors, patients overactivated left
      ventrolateral prefrontal cortex. This overactivation may reflect hypersensitivity
      to salient stimuli in schizophrenia. Patients also exhibited an inverse
      correlation between negative symptom severity and activation to novel distractors
      in the dorsolateral prefrontal cortex, premotor area, and ventral striatum.
      Novelty-induced activity within prefrontal cortex and ventral striatum may
      represent a useful intermediate phenotype for studies of negative symptoms.

PMID- 19756229
TI  - ergm: A Package to Fit, Simulate and Diagnose Exponential-Family Models for
      Networks.
AB  - We describe some of the capabilities of the ergm package and the statistical
      theory underlying it. This package contains tools for accomplishing three
      important, and interrelated, tasks involving exponential-family random graph
      models (ERGMs): estimation, simulation, and goodness of fit. More precisely, ergm
      has the capability of approximating a maximum likelihood estimator for an ERGM
      given a network data set; simulating new network data sets from a fitted ERGM
      using Markov chain Monte Carlo; and assessing how well a fitted ERGM does at
      capturing characteristics of a particular network data set.

PMID- 19756231
TI  - Scalable isosurface visualization of massive datasets on commodity off-the-shelf
      clusters.
AB  - Tomographic imaging and computer simulations are increasingly yielding massive
      datasets. Interactive and exploratory visualizations have rapidly become
      indispensable tools to study large volumetric imaging and simulation data. Our
      scalable isosurface visualization framework on commodity off-the-shelf clusters
      is an end-to-end parallel and progressive platform, from initial data access to
      the final display. Interactive browsing of extracted isosurfaces is made possible
      by using parallel isosurface extraction, and rendering in conjunction with a new
      specialized piece of image compositing hardware called Metabuffer. In this paper,
      we focus on the back end scalability by introducing a fully parallel and out-of
      core isosurface extraction algorithm. It achieves scalability by using both
      parallel and out-of-core processing and parallel disks. It statically partitions
      the volume data to parallel disks with a balanced workload spectrum, and builds
      I/O-optimal external interval trees to minimize the number of I/O operations of
      loading large data from disk. We also describe an isosurface compression scheme
      that is efficient for progress extraction, transmission and storage of
      isosurfaces.

PMID- 19756232
TI  - TESTING SIGNIFICANCE OF FEATURES BY LASSOED PRINCIPAL COMPONENTS.
AB  - We consider the problem of testing the significance of features in high
      dimensional settings. In particular, we test for differentially-expressed genes
      in a microarray experiment. We wish to identify genes that are associated with
      some type of outcome, such as survival time or cancer type. We propose a new
      procedure, called Lassoed Principal Components (LPC), that builds upon existing
      methods and can provide a sizable improvement. For instance, in the case of two
      class data, a standard (albeit simple) approach might be to compute a two-sample
      t-statistic for each gene. The LPC method involves projecting these conventional
      gene scores onto the eigenvectors of the gene expression data covariance matrix
      and then applying an L(1) penalty in order to de-noise the resulting projections.
      We present a theoretical framework under which LPC is the logical choice for
      identifying significant genes, and we show that LPC can provide a marked
      reduction in false discovery rates over the conventional methods on both real and
      simulated data. Moreover, this flexible procedure can be applied to a variety of
      types of data and can be used to improve many existing methods for the
      identification of significant features.

PMID- 19756233
TI  - Numerical simulations of non-spherical bubble collapse.
AB  - A high-order accurate shock- and interface-capturing scheme is used to simulate
      the collapse of a gas bubble in water. In order to better understand the damage
      caused by collapsing bubbles, the dynamics of the shock-induced and Rayleigh
      collapse of a bubble near a planar rigid surface and in a free field are
      analysed. Collapse times, bubble displacements, interfacial velocities and
      surface pressures are quantified as a function of the pressure ratio driving the
      collapse and of the initial bubble stand-off distance from the wall; these
      quantities are compared to the available theory and experiments and show good
      agreement with the data for both the bubble dynamics and the propagation of the
      shock emitted upon the collapse. Non-spherical collapse involves the formation of
      a re-entrant jet directed towards the wall or in the direction of propagation of
      the incoming shock. In shock-induced collapse, very high jet velocities can be
      achieved, and the finite time for shock propagation through the bubble may be non
      negligible compared to the collapse time for the pressure ratios of interest.
      Several types of shock waves are generated during the collapse, including
      precursor and water-hammer shocks that arise from the re-entrant jet formation
      and its impact upon the distal side of the bubble, respectively. The water-hammer
      shock can generate very high pressures on the wall, far exceeding those from the
      incident shock. The potential damage to the neighbouring surface is quantified by
      measuring the wall pressure. The range of stand-off distances and the surface
      area for which amplification of the incident shock due to bubble collapse occurs
      is determined.

PMID- 19756234
TI  - Structural characterization and expression analysis of the SERK/SERL gene family
      in rice (Oryza sativa).
AB  - Somatic embryogenesis (SE) is the developmental restructuring of somatic cells
      towards the embryogenic pathway and forms the basis of cellular totipotency in
      angiosperms. With the availability of full-length cDNA sequences from Knowledge
      based Oryza Molecular Biological Encylopedia (KOME), we identified the leucine
      rich repeat receptor-like kinase (LRR-RLK) genes from rice (Oryza sativa), which
      also encompasses genes involved in regulating somatic embryogenesis. Eight out of
      eleven of the rice SERK and SERL (SERK-like) genes have the TIGR annotation as
      (putative) brassinosteroid insensitive 1-associated receptor kinase (precursor).
      Real-time polymerase chain reaction analysis was undertaken to quantify
      transcript levels of these 11 genes. Most of these genes were upregulated by
      brassinosteroids although only a few of these displayed auxin induction. The
      expression profile of these genes is nearly uniform in the zygotic embryogenic
      tissue, but the expression pattern is more complex in the somatic embryogenic
      tissue. It is likely that OsSERKs and OsSERLs may be involved in somatic
      embryogenesis and also perform a role in morphogenesis and various other plant
      developmental processes. Functional validation of these somatic embryogenesis
      receptor-like kinase genes may help in elucidating their precise functions in
      regulating various facets of plant development.

PMID- 19756235
TI  - Compatibility of Medical-Grade Polymers with Dense CO(2).
AB  - This study reports the effect of exposure to liquid carbon dioxide on the
      mechanical properties of selected medical polymers. The tensile strengths and
      moduli of fourteen polymers are reported. Materials were exposed to liquid CO(2),
      or CO(2) + trace amounts of aqueous H(2)O(2), at 6.5 MPa and ambient temperature.
      Carbon dioxide uptake, swelling, and distortion were observed for the more
      amorphous polymers while polymers with higher crystallinity showed little effect
      from CO(2) exposure. Changes in tensile strength were not statistically
      significant for most plastics, and most indicated good tolerance to liquid CO(2).
      These results are relevant to evaluating the potential of liquid CO(2)-based
      sterilization technology.

PMID- 19756237
TI  - Externalities in the Workplace: A Response to a Rejoinder to a Response to a
      Response to a Paper.
AB  - Professor Henderson has simply repeated the same two points he made in his
      earlier critique (Henderson 2007) of our article "Smoke-free Ordinances Increase
      Restaurant Profit and Value" (Alamar and Glantz 2004). He argues 1.) that
      secondhand smoke is not an externality, therefore no government intervention is
      required to protect workers and customers in restaurants and bars, and 2.) the
      empirical results in the paper are not conclusive because the data are cross
      sectional. Henderson also issues a challenge for us to advocate for the repeal of
      the California law on smoke-free restaurants. While we enjoy a good debate and do
      not mind adding another publication to our CVs, we do hope that Prof. Henderson
      will not find the burning desire to restate his position again, after we respond
      this last time.

PMID- 19756236
TI  - Effects of pulse width and electrode placement on the efficacy and cognitive
      effects of electroconvulsive therapy.
AB  - BACKGROUND: While electroconvulsive therapy (ECT) in major depression is
      effective, cognitive effects limit its use. Reducing the width of the electrical
      pulse and using the right unilateral electrode placement may decrease adverse
      cognitive effects, while preserving efficacy. METHODS: In a double-masked study,
      we randomly assigned 90 depressed patients to right unilateral ECT at 6 times
      seizure threshold or bilateral ECT at 2.5 times seizure threshold, using either a
      traditional brief pulse (1.5 ms) or an ultrabrief pulse (0.3 ms). Depressive
      symptoms and cognition were assessed before, during, and immediately, two, and
      six months after therapy. Patients who responded were followed for a one-year
      period. RESULTS: The final remission rate for ultrabrief bilateral ECT was 35
      percent, compared with 73 percent for ultrabrief unilateral ECT, 65 percent for
      standard pulse width bilateral ECT, and 59 percent for standard pulse width
      unilateral ECT (all P's<0.05 after covariate adjustment). The ultrabrief right
      unilateral group had less severe cognitive side effects than the other 3 groups
      in virtually all primary outcome measures assessed in the acute postictal period,
      and during and immediately following therapy. Both the ultrabrief stimulus and
      right unilateral electrode placement produced less short- and long-term
      retrograde amnesia. Patients rated their memory deficits as less severe following
      ultrabrief right unilateral ECT compared to each of the other three conditions
      (P<0.001). CONCLUSIONS: The use of an ultrabrief stimulus markedly reduces
      adverse cognitive effects, and when coupled with markedly suprathreshold right
      unilateral ECT, also preserves efficacy. (ClinicalTrials.gov number,
      NCT00487500.).

PMID- 19756238
TI  - Revising the Tool for Assessing Cultural Competence Training (TACCT) for
      curriculum evaluation: Findings derived from seven US schools and expert
      consensus.
AB  - BACKGROUND: The 67-item TACCT currently used for needs assessment has potential
      for evaluating evolving cultural competence (CC) curricula. PURPOSE: To validate
      a shortened, more practical TACCT measure. METHODS: The 67-item TACCT was
      administered to students and course directors at 7 US schools. Course directors
      and students reported which of 67 TACCT items were taught. Intraclass correlation
      coefficients (ICC) examined faculty-student agreement. Under-addressed content
      was identified. A new and shortened TACCT configuration was proposed and
      validated with expert educator input. RESULTS: Across-school faculty and student
      response rates ranged from 75% to 100%. Aggregate ICC was 0.90 (95% CI: 0.84,
      0.94) for the 67-item TACCT demonstrating faculty-student agreement. Experts
      agreed on reduction from 67 to 42 items and domain revision from five to six
      domains to match under-addressed content. Item analysis showed high internal
      consistency for all 6 new domains and the total revised 42-item TACCT.
      CONCLUSIONS: A shorter, more practical TACCT measure is valid and reliable and
      focuses on under-addressed CC content. Use for curricular evaluation is
      suggested.

PMID- 19756239
TI  - The Role of Inflammation in the Pathogenesis of Colorectal Cancer.
AB  - Chronic inflammatory disorders are often associated with an increased risk of
      developing cancer. A classic example of the connection between inflammation and
      cancer is the increased risk of colorectal cancer in patients with inflammatory
      bowel disease (IBD). In this review, we discuss aspects of IBD that promote
      colorectal cancer and highlight key molecular mediators that contribute to cancer
      risk. Additionally, we report on progress in identifying molecular targets that
      may prove efficacious in blocking the progression of IBD-related inflammation to
      cancer.

PMID- 19756240
TI  - Enhancement of Pavlovian conditioned inhibition achieved by posttraining
      inflation of the training excitor.
AB  - In two conditioned lick suppression experiments using water-deprived rats, we
      examined the effects of following Pavlovian conditioned inhibition training
      (i.e., A-US/AX-NoUS) with pairings of the training excitor (A) and the
      unconditioned stimulus (US). Experiments 1 and 2 assessed the effects of this
      posttraining inflation treatment on Pavlovian conditioned inhibition using a
      summation test and a retardation test, respectively. Both experiments revealed
      that subjects exposed to inflation treatment demonstrated behavior indicative of
      enhanced conditioned inhibition compared to subjects that did not receive
      inflation treatment. The results in conjunction with other recent findings
      suggest that posttraining associative deflation (i.e., extinction of A) and
      inflation effects are more symmetrical than has previously been realized.

PMID- 19756241
TI  - Surface Analysis of Photolithographic Patterns using ToF-SIMS and PCA.
AB  - Time-of-flight secondary ion mass spectrometry (ToF-SIMS) is a surface analysis
      technique well-suited to detect and identify trace surface species. With the
      latest analyzers, ion sources and data analysis methods, imaging ToF-SIMS
      provides detailed 2-D and 3-D surface reactivity maps. Coupling multivariate
      analysis methods such as principal component analysis (PCA) with ToF-SIMS
      provides a powerful method for differentiating spatial regions with different
      chemistries. ToF-SIMS and PCA are used in this study to image and analyze a two
      component photolithograph-patterned surface chemistry currently published and
      commercialized for bioassays, bio-chips and cell-based biosensors. A widely used
      reactive surface coupling chemistry, N-hydroxysuccinimide (NHS), and 2
      methoxyethylamine (MeO) were co-patterned into adjacent regions on a commercial
      microarray polymer coating using standard photolithography methods involving
      deposition, patterning and removal of a routinely used photoresist material.
      After routine processing, ToF-SIMS and PCA of the patterned surface revealed
      significant residual photoresist material remaining at the interface of the
      NHS/MeO patterns, as well as lower concentrations of residual photoresist
      material remaining within the MeO-containing regions, providing spatial mapping
      and residue analysis not evident from other characterization techniques. As
      detection of surface photoresist residue remains an inherent challenge in
      photolithographic processing of a wide array of materials, the use of ToF-SIMS
      coupled with PCA is shown to be a high-resolution characterization tool with the
      high sensitivity and specificity required for surface quality control
      measurements following photolithography and pattern development relevant to many
      current processes.

PMID- 19756243
TI  - Segmentation of Brain Immunohistochemistry Images Using Clustering of Linear
      Centroids and Regional Shapes.
AB  - A generalized clustering algorithm utilizing the geometrical shapes of clusters
      for segmentation of colored brain immunohistological images is presented. To
      simplify the computation, the dimension of vectors composed from the pixel RGB
      components is reduced from three to two by applying a de-correlation mapping with
      the orthogonal bases of the eigenvectors of the auto-covariance matrix. Since the
      brain immunohistochemical images have stretched clusters that appear long and
      narrow in geometrical shape, we use centroids of straight lines instead of single
      points to approximate the clusters. An iterative algorithm is developed to
      optimize the linear centroids by minimizing the approximation mean-squared error.
      The partitioning of the two-dimensional vector domain into three portions
      classifies each image pixel into one of the three classes: The microglial cell
      cytoplasm, the combined hematoxylin stained cell nuclei and the neuropil, and the
      pale background. Regions of the combined hematoxylin stained cell nuclei and the
      neuropil are to be separated based on the differences in their regional shapes.
      The segmentation results of real immunohistochemical images of brain microglia
      are provided and discussed.

PMID- 19756242
TI  - Corruption of innate immunity by bacterial proteases.
AB  - The innate immune system of the human body has developed numerous mechanisms to
      control endogenous and exogenous bacteria and thus prevent infections by these
      microorganisms. These mechanisms range from physical barriers such as the skin or
      mucosal epithelium to a sophisticated array of molecules and cells that function
      to suppress or prevent bacterial infection. Many bacteria express a variety of
      proteases, ranging from non-specific and powerful enzymes that degrade many
      proteins involved in innate immunity to proteases that are extremely precise and
      specific in their mode of action. Here we have assembled a comprehensive picture
      of how bacterial proteases affect the host's innate immune system to gain
      advantage and cause infection. This picture is far from being complete since the
      numbers of mechanisms utilized are as astonishing as they are diverse, ranging
      from degradation of molecules vital to innate immune mechanisms to subversion of
      the mechanisms to allow the bacterium to hide from the system or take advantage
      of it. It is vital that such mechanisms are elucidated to allow strategies to be
      developed to aid the innate immune system in controlling bacterial infections.

PMID- 19756244
TI  - Strategies for therapeutic repair: The "R(3)" regenerative medicine paradigm.
AB  - Beyond the palliative reach of today, medical therapies of tomorrow aim to treat
      the root cause of chronic degenerative diseases. Therapeutic repair encompasses
      the converging triad of rejuvenation, regeneration or replacement strategies that
      rely on self-healing processes, stem cell regeneration, and/or organ
      transplantation. Natural healing or rejuvenation exemplify inherent, baseline
      repair secured by tissue self-renewal and de novo cell biogenesis, particularly
      effective in organs with a high endogenous reparative capacity. Transplant
      medicine exploits the replacement strategy as a valuable option to recycle used
      parts and restore failing organ function by means of exogenous substitutes-it is,
      however, limited by donor shortage. Stem cell-based regeneration offers the next
      frontier of medical therapy through delivery of essentially unlimited pools of
      autologous or allogeneic, naive or modified, progenitor cells to achieve
      structural and functional repair. Translation into clinical applications requires
      the establishment of a regenerative medicine community of practice capable to
      bridge discovery with personalized treatment solutions. Indeed, this
      multidisciplinary specialized workforce will be capable to integrate the new
      science of embryology, immunology, and stem cell biology into bioinformatics and
      network medicine platforms, ensuring implementation of therapeutic repair
      strategies into individualized disease management algorithms.

PMID- 19756246
TI  - An Empirical Evaluation of the Use of Fixed Cutoff Points in RMSEA Test Statistic
      in Structural Equation Models.
AB  - This article is an empirical evaluation of the choice of fixed cutoff points in
      assessing the root mean square error of approximation (RMSEA) test statistic as a
      measure of goodness-of-fit in Structural Equation Models. Using simulation data,
      the authors first examine whether there is any empirical evidence for the use of
      a universal cutoff, and then compare the practice of using the point estimate of
      the RMSEA alone versus that of using it jointly with its related confidence
      interval. The results of the study demonstrate that there is little empirical
      support for the use of .05 or any other value as universal cutoff values to
      determine adequate model fit, regardless of whether the point estimate is used
      alone or jointly with the confidence interval. The authors' analyses suggest that
      to achieve a certain level of power or Type I error rate, the choice of cutoff
      values depends on model specifications, degrees of freedom, and sample size.

PMID- 19756247
TI  - An Effective Algorithm for Generation of Factorial Designs with Generalized
      Minimum Aberration.
AB  - Fractional factorial designs are popular and widely used for industrial
      experiments. Generalized minimum aberration is an important criterion recently
      proposed for both regular and non-regular designs. This paper provides a formal
      optimization treatment on optimal designs with generalized minimum aberration.
      New lower bounds and optimality results are developed for resolution-III designs.
      Based on these results, an effective computer search algorithm is provided for
      sub-design selection, and new optimal designs are reported.

PMID- 19756245
TI  - Innate immunity to influenza virus: implications for future therapy.
AB  - Innate immunity is critical in the early containment of influenza virus
      infection. The innate response is surprisingly complex. A variety of soluble
      innate inhibitors in respiratory secretions provide an initial barrier to
      infection. Dendritic cells, phagocytes and natural killer cells mediate viral
      clearance and promote further innate and adaptive responses. Toll-like receptors
      3 and 7 and cytoplasmic RNA sensors are critical for activating these responses.
      In general, the innate response restricts viral replication without injuring the
      lung; however, the 1918 pandemic and H5N1 strains cause more profound, possibly
      harmful, innate responses. In this review, we discuss the implications of
      burgeoning knowledge of innate immunity for therapy of influenza.

PMID- 19756248
TI  - Models for Value-Added Modeling of Teacher Effects.
AB  - The use of complex value-added models that attempt to isolate the contributions
      of teachers or schools to student development is increasing. Several variations
      on these models are being applied in the research literature, and policy makers
      have expressed interest in using these models for evaluating teachers and
      schools. In this article, we present a general multivariate, longitudinal mixed
      model that incorporates the complex grouping structures inherent to longitudinal
      student data linked to teachers. We summarize the principal existing modeling
      approaches, show how these approaches are special cases of the proposed model,
      and discuss possible extensions to model more complex data structures. We present
      simulation and analytical results that clarify the interplay between estimated
      teacher effects and repeated outcomes on students over time. We also explore the
      potential impact of model misspecifications, including missing student covariates
      and assumptions about the accumulation of teacher effects over time, on key
      inferences made from the models. We conclude that mixed models that account for
      student correlation over time are reasonably robust to such misspecifications
      when all the schools in the sample serve similar student populations. However,
      student characteristics are likely to confound estimated teacher effects when
      schools serve distinctly different populations.

PMID- 19756249
TI  - Co-Occurring Sexual Risk and Substance Use Behaviors Among Incarcerated
      Adolescents.
AB  - Incarcerated adolescents report greater sexual risk than do nonincarcerated
      peers. High-risk sexual behavior is associated with substance use. To determine
      how much sexual risk is combined with substance use, 167 incarcerated adolescents
      reported on their sexual risk behavior in the year before incarceration that
      involved alcohol or marijuana. For each risk behavior, marijuana use was more
      likely than was alcohol use. Marijuana use was more common for higher risk
      behaviors than for lower risk behaviors. Periods of incarceration provide
      opportunities for intervening on HIV-relevant risk behaviors among adolescents.
      The context of substance use within high-risk sexual situations ought to be a
      focus of interventions for incarcerated adolescents.

PMID- 19756250
TI  - Piloting the Family Check-Up With Incarcerated Adolescents and Their Parents.
AB  - The purpose of the current investigation was to pilot the Family Check-Up (FCU;
      see T. J. Dishion & K. Kavanagh, 2003) with 10 incarcerated adolescents and their
      parents or guardians. The FCU is based on principles of motivational interviewing
      (W. R. Miller & S. Rollnick, 2002). The authors delivered FCU with a high degree
      of fidelity and adherence on the basis of ratings from parents, therapists, and
      observers. Results suggest that the FCU positively impacted families (effect
      sizes were generally in the medium range). After our intervention, adolescents
      were more confident in their ability to resist drug use, and parents were more
      confident in their ability to impact their adolescents' risky behaviors. Parents
      and adolescents both reported being highly satisfied with this intervention.
      These results warrant further investigation of the FCU with incarcerated
      adolescents and their families in a controlled clinical trial.

PMID- 19756251
TI  - The optimal level of fuzz: Case studies in a methodology for psychological
      research.
AB  - Cognitive Science research is hard to conduct, because researchers must take
      phenomena from the world and turn them into laboratory tasks for which a
      reasonable level of experimental control can be achieved. Consequently, research
      necessarily makes tradeoffs between internal validity (experimental control) and
      external validity (the degree to which a task represents behavior outside of the
      lab). Researchers are thus seeking the best possible tradeoff between these
      constraints, which we refer to as the optimal level of fuzz. We present two
      principles for finding the optimal level of fuzz, in research, and then
      illustrate these principles using research from motivation, individual
      differences, and cognitive neuroscience.

PMID- 19756252
TI  - Astrocytic 'power-grid': Delivery upon neuronal demand.
AB  - Gap junctions can connect the cytosolic compartments of adjacent astroglia. They
      allow intercellular flux of low-molecular weight (< ~ 1 kDa) compounds, including
      metabolites and second messengers. Only recently, however, has it been proposed
      that gap junctions may serve an additional role in the astrocytic metabolic
      network which maintains synaptic transmission. The brain seems to be using a
      strategy analogous to power-grid systems used in modern societies to supply
      energy; the astrocytic 'power-grid' can deliver the metabolic energy to neurons
      as needed. Such an astroglial energy grid is malleable and can change the size
      and shape in response to metabolic activity of neuronal network to deliver energy
      from the root source of energy of the brain, the blood glucose, to neurons.

PMID- 19756253
TI  - A Survey of Hospices Use of Complementary Therapy.
AB  - As people live longer with chronic illnesses, the need for hospice services will
      increase. Complementary therapies have been shown to increase ease, relieve pain,
      and improve quality of life; all relevant for people with chronic illness at the
      end of their lives. The first aim of this study was to identify complementary
      therapy services available to, and provided for, clients receiving hospice care
      in Nevada and Montana. The second aim was to identify differences in those
      therapies for urban and rural hospice clients. Using a descriptive survey design,
      data were collected from surveys sent to all hospice administrators in Nevada and
      Montana (N=54). A 50% (n=27) response rate was obtained. Most (70.4%, n=19) of
      the participating hospices offered complementary therapy; slightly more than half
      (52.9%, n=9) provided the services for less than 25% of their clients. No
      significant differences were found between rural and urban hospices.

PMID- 19756254
TI  - Forster Resonance Energy Transfer and Conformational Stability of Proteins: An
      Advanced Biophysical Module for Physical Chemistry Students.
AB  - Protein folding is an exploding area of research in biophysics and physical
      chemistry. Here, we describe the integration of several techniques, including
      absorption spectroscopy, fluorescence spectroscopy, and Forster resonance energy
      transfer (FRET) measurements, to probe important topics in protein folding.
      Cytochrome c is used as a model protein; comparison of conformational stabilities
      ( DeltaGH2O?) measured via two chemical denaturants, urea and guanidinium
      hydrochloride, illustrate important concepts in protein folding and
      intermolecular interactions. In addition, the determination of intraprotein
      distances based upon the FRET pair Trp-59 and the heme group for unfolded states
      of cytochrome c highlights the evolution of the protein structure under unfolding
      conditions. Analysis and discussion of these results provide opportunities to
      gain in-depth understanding of models for protein folding while enhancing
      students' skills with optical techniques. Collectively, the combination of
      optical spectroscopy, rigorous quantitative analysis, and a focus on biophysics
      illustrates the significance of fundamental research at the growing intersection
      of chemistry, biology, and physics.

PMID- 19756255
TI  - A Multilayer MEMS Platform for Single-Cell Electric Impedance Spectroscopy and
      Electrochemical Analysis.
AB  - The fabrication and characterization of a microchamber electrode array for
      electrical and electrochemical studies of individual biological cells are
      presented. The geometry was tailored specifically for measurements from sensory
      hair cells isolated from the cochlea of the mammalian inner ear. Conventional
      microelectromechanical system (MEMS) fabrication techniques were combined with a
      heat-sealing technique and polydimethylsiloxane micromolding to achieve a
      multilayered microfluidic system that facilitates cell manipulation and
      selection. The system allowed for electrical stimulation of individual living
      cells and interrogation of excitable cell membrane dielectric properties as a
      function of space and time. A three-electrode impedimetric system was
      incorporated to provide the additional ability to record the time-dependent
      concentrations of specific biochemicals in microdomain volumes near identified
      regions of the cell membrane. The design and fabrication of a robust fluidic and
      electrical interface are also described. The interface provided the flexibility
      and simplicity of a "cartridge-based" approach in connecting to the MEMS devices.
      Cytometric measurement capabilities were characterized by using electric
      impedance spectroscopy (1 kHz-10 MHz) of isolated outer hair cells. Chemical
      sensing capability within the microchannel recording chamber was characterized by
      using cyclic voltammetry with varying concentrations of potassium ferricyanide
      (K(3)Fe(CN)(6)). Chronoamperometric recordings of electrically stimulated PC12
      cells highlight the ability of the platform to resolve exocytosis events from
      individual cells.

PMID- 19756256
TI  - Nonlinear Random Effects Mixture Models: Maximum Likelihood Estimation via the EM
      Algorithm.
AB  - Nonlinear random effects models with finite mixture structures are used to
      identify polymorphism in pharmacokinetic/pharmacodynamic phenotypes. An EM
      algorithm for maximum likelihood estimation approach is developed and uses
      sampling-based methods to implement the expectation step, that results in an
      analytically tractable maximization step. A benefit of the approach is that no
      model linearization is performed and the estimation precision can be arbitrarily
      controlled by the sampling process. A detailed simulation study illustrates the
      feasibility of the estimation approach and evaluates its performance.
      Applications of the proposed nonlinear random effects mixture model approach to
      other population pharmacokinetic/pharmacodynamic problems will be of interest for
      future investigation.

PMID- 19756257
TI  - PML: An emerging tumor suppressor and a target with therapeutic potential.
AB  - Though originally discovered as a tumor suppressor in Acute Promyelocytic
      Leukemia (APL), the importance of promyelocytic leukemia protein (PML) in cancers
      of other origins has not been widely studied. Recent studies have shown that
      multiple types of cancers show decreased expression of PML protein, though the
      mechanisms leading to this down-regulation are unknown. Decreased expression of
      PML can result in loss of cell cycle control and prevention of apoptosis and is
      likely a key event in the promotion of oncogenesis. Many of these effects are due
      to changes in the transcriptional profile of the cell as a result of decreased
      size and number of PML nuclear bodies. Several mouse studies confirm the
      contribution of PML to oncogenesis and cancer progression. It is important to not
      only further define a role for PML as a tumor suppressor, but also to begin to
      develop strategies to target PML therapeutically.

PMID- 19756258
TI  - Isolated Hypoglossal Nerve Palsy due to Infected Impacted Tooth.
AB  - Case of isolated hypoglossal nerve palsy is an extremely rare condition. There
      are several causes that can be attributed to it. We present a case where a
      patient presented herself with swelling on the right side of her cheek extending
      to the floor of the mouth, with unilateral right hypoglossal nerve palsy. Removal
      of the impacted tooth resulted in the improvement of function of the hypoglossal
      nerve. The transient isolated hypoglossal nerve palsy could have been due to the
      infected impacted tooth. Therefore, the dentist or doctors coming across with
      isolated hypoglossal nerve palsy should consider the infected impacted tooth as
      the differential diagnosis.

PMID- 19756259
TI  - Modification of the NEMA XR21-2000 cardiac phantom for testing of imaging systems
      used in endovascular image guided interventions.
AB  - X-ray equipment testing using phantoms that mimic the specific human anatomy,
      morphology, and structure is a very important step in the research, development,
      and routine quality assurance for such equipment. Although the NEMA XR21 phantom
      exists for cardiac applications, there is no such standard phantom for neuro-,
      peripheral and cardio-vascular angiographic applications. We have extended the
      application of the NEMA XR21-2000 phantom to evaluate neurovascular x-ray imaging
      systems by structuring it to be head-equivalent; two aluminum plates shaped to
      fit into the NEMA phantom geometry were added to a 15 cm thick section. Also, to
      enable digital subtraction angiography (DSA) testing, two replaceable central
      plates with a hollow slot were made so that various angiographic sections could
      be inserted into the phantom. We tested the new modified phantom using a flat
      panel C-arm unit dedicated for endovascular image-guided interventions. All NEMA
      XR21-2000 standard test sections were used in evaluations with the new "head
      equivalent" phantom. DSA and DA are able to be tested using two standard
      removable blocks having simulated arteries of various thickness and iodine
      concentrations (AAPM Report 15). The new phantom modifications have the benefits
      of enabling use of the standard NEMA phantom for angiography in both neuro- and
      cardio-vascular applications, with the convenience of needing only one versatile
      phantom for multiple applications. Additional benefits compared to using multiple
      phantoms are increased portability and lower cost.

PMID- 19756260
TI  - Tomosynthesis via Total Variation Minimization Reconstruction and Prior Image
      Constrained Compressed Sensing (PICCS) on a C-arm System.
AB  - Recently, foundational mathematical theory, compressed sensing (CS), has been
      developed which enables accurate reconstruction from greatly undersampled
      frequency information (Candes et. al. and Donoho). Using numerical phantoms it
      has been demonstrated that CS reconstruction (e.g. minimizing the l1 norm of the
      discrete gradient of the image) offers promise for computed tomography. However,
      when using experimental CT projection data the undersampling factors enabled were
      smaller than in numerical simulations. An extension to CS has recently been
      proposed wherein a prior image is utilized as a constraint in the image
      reconstruction procedure (i.e. Prior Image Constrained Compressed Sensing -
      PICCS). Experimental results are demonstrated here from a clinical C-arm system,
      highlighting one application of PICCS in reducing radiation exposure during
      interventional procedures while preserving high image quality. In this study a
      range of view angles has been investigated from very limited angle aquisitions
      (e.g. tomosythesis) to undersampled CT acquisitions.

PMID- 19756261
TI  - Convenient oxidation of benzylic and allylic halides to aldehydes and ketones.
AB  - Benzylic and allylic halides were conveniently oxidized to aldehydes and ketones
      by pyridine N-oxide in the presence of silver oxide under mild conditions.

PMID- 19756262
TI  - Dynamic Clamp Analysis of Synaptic Integration in Sympathetic Ganglia.
AB  - Advances in modern neuroscience require the identification of principles that
      connect different levels of experimental analysis, from molecular mechanisms to
      explanations of cellular functions, then to circuits, and, ultimately, to systems
      and behavior. Here, we examine how synaptic organization of the sympathetic
      ganglia may enable them to function as use-dependent amplifiers of preganglionic
      activity and how the gain of this amplification may be modulated by metabotropic
      signaling mechanisms. The approach combines a general computational model of
      ganglionic integration together with experimental tests of the model using the
      dynamic clamp method. In these experiments, we recorded intracellularly from
      dissociated bullfrog sympathetic neurons and then mimicked physiological synapses
      with virtual computer-generated synapses. It thus became possible to analyze the
      synaptic gain by recording cellular responses to complex patterns of synaptic
      activity that normally arise in vivo from convergent nicotinic and muscarinic
      synapses. The results of these studies are significant because they illustrate
      how gain generated through ganglionic integration may contribute to the feedback
      control of important autonomic behaviors, in particular to the control of the
      blood pressure. We dedicate this paper to the memory of Professor Vladimir Skok,
      whose rich legacy in synaptic physiology helped establish the modern paradigm for
      connecting multiple levels of analysis in studies of the nervous system.

PMID- 19756263
TI  - High-speed ultrahigh-resolution optical coherence tomography findings in chronic
      solar retinopathy.
AB  - PURPOSE: To describe ocular findings for a 34-year-old man with chronic solar
      retinopathy using high-speed ultrahigh-resolution (UHR) optical coherence
      tomography (OCT). METHODS: Fundus photography, fluorescein angiography, and
      Stratus OCT (Carl Zeiss Meditec, Inc., Dublin, CA) were performed. A high-speed
      UHR OCT prototype developed in our ophthalmology clinic was used to obtain
      detailed images of the retina. PATIENTS: Two eyes of one patient with chronic
      solar retinopathy were studied. RESULTS: Both Stratus OCT and high-speed UHR OCT
      demonstrated foveal thinning bilaterally. In addition, high-speed UHR OCT showed
      distinct hyporeflective disruptions in the photoreceptor inner segment/outer
      segment junction and photoreceptor outer segments bilaterally. En face OCT images
      from three-dimensional OCT data sets revealed hyporeflective regions of
      photoreceptor atrophy in the outer retina. CONCLUSIONS: High-speed UHR OCT showed
      more detail than standard OCT, and findings were consistent with histopathologic
      and ultrastructural features that have been reported previously. Solar
      retinopathy should be studied further with high-speed UHR OCT to determine the
      short- and long-term effects of solar radiation damage.

PMID- 19756266
TI  - Nitrile groups as vibrational probes of biomolecular structure and dynamics: an
      overview.
AB  - This paper presents an overview of recent experiments and theoretical
      developments aimed at using vibrational spectroscopy to understand the structure
      and dynamics of nitrile-labeled biomolecules. Nitrile groups are excellent
      vibrational probes of proteins and DNA because they absorb in a region of the
      spectrum that is relatively free of absorption due to the biomolecule, and they
      have high extinction coefficients. The vibrational frequency of nitrile groups is
      also extraordinarily sensitive to its local environment, and thus C[triple bond,
      length as m-dash]N bonds have been employed in both linear and 2-D infrared (IR)
      spectroscopy experiments and also as vibrational Stark probes of electric fields
      in proteins. The interpretation and design of these experiments would be enhanced
      by accurate calculations of IR spectra from molecular dynamics simulations.
      Recently, theoretical developments towards computing the vibrational spectrum of
      nitrile groups in the condensed-phase have been highly successful. A strong
      synergy between experiment and theory will further promote the use of vibrational
      spectroscopy of nitrile-labeled biomolecules to address fundamental questions of
      structure and dynamics that are elusive to other techniques.

PMID- 19756267
TI  - Elucidation of oxyanion coordination geometries at solid surfaces of varied
      electric field strengths.
AB  - Density functional theory calculations of oxyanions exposed to external electric
      fields revealed systematic variations in molecular geometries and vibration
      stretching frequencies. These variations can be used in laboratory studies to
      determine coordination geometries of oxyanions adsorbed on solid surfaces using
      infrared spectroscopy.

PMID- 19756268
TI  - Energy driven self-organization in nanoscale metallic liquid films.
AB  - Nanometre thick metallic liquid films on inert substrates can spontaneously dewet
      and self-organize into complex nanomorphologies and nanostructures with well
      defined length scales. Nanosecond pulses of an ultraviolet laser can capture the
      dewetting evolution and ensuing nanomorphologies, as well as introduce dramatic
      changes to dewetting length scales due to the nanoscopic nature of film heating.
      Here, we show theoretically that the self-organization principle, based on
      equating the rate of transfer of thermodynamic free energy to rate of loss in
      liquid flow, accurately describes the spontaneous dewetting. Experimental
      measurements of laser dewetting of Ag and Co liquid films on SiO(2) substrates
      confirm this principle. This energy transfer approach could be useful for
      analyzing the behavior of nanomaterials and chemical processes in which
      spontaneous changes are important.

PMID- 19756269
TI  - Electrochemical studies of capacitance in cerium oxide thin films and its
      relationship to anionic and electronic defect densities.
AB  - Small polaron carrier density in epitaxial, doped CeO(2) thin films under low
      oxygen partial pressure was determined from electrochemically-measured
      capacitance after accounting for interfacial effects and shown to agree well with
      bulk values.

PMID- 19756270
TI  - A low temperature investigation of the N(4S degrees) + NO reaction.
AB  - The kinetics of the N((4)S degrees) + NO(X(2)Pi) reaction have been studied in a
      continuous supersonic flow reactor over the range 48 K <or= T <or= 211 K.
      Nitrogen atoms were produced by microwave discharge upstream of the Laval nozzle
      and were probed in the vacuum ultraviolet by resonance fluorescence. The reaction
      has been found to exhibit a small negative temperature dependence, with a rate
      coefficient decreasing from (5.8 +/- 0.3) x 10(-11) cm(3) molecule(-1) s(-1) at
      48 K to (3.3 +/- 0.2) x 10(-11) cm(3) molecule(-1) s(-1) at 211 K with the
      statistical uncertainties cited at the level of a single standard deviation from
      the mean.

PMID- 19756271
TI  - The reactivity of CO2 with K atoms adsorbed on MgO powders.
AB  - In this combined quantum chemical and EPR study we have investigated the
      formation of CO(2)(-) radicals by contact of CO(2) molecules with a K precovered
      MgO surface. K atoms have been deposited on polycrystalline MgO samples, and then
      exposed to CO(2). The typical EPR signal of the isolated K atoms disappears when
      the reaction with CO(2) takes place and a new paramagnetic species attributed to
      CO(2)(-) is observed. DFT cluster model calculations show that there is a
      spontaneous electron transfer from the adsorbed K atom to the CO(2) molecule,
      with formation of K(+)CO(2)(-) surface complexes. These species have the same
      electronic characteristics and spin distribution of gas-phase M(+)CO(2)(-) (M =
      Li, Na, K) molecules, but are stabilized by the presence of the ionic surface.
      The most stable MgO sites where the adsorption of CO(2) occurs and the computed
      EPR properties are discussed.

PMID- 19756272
TI  - Energetic and electronic properties of X- (Si, Ge, Sn, Pb) doped TiO2 from first
      principles.
AB  - First-principles density functional theory calculations were performed on the
      electronic properties of substitutional Si, Ge, Sn, and Pb-doped rutile and
      anatase TiO(2), where Ti was replaced by dopants, to explore the effect of the
      dopants on the band edges and their possible efficacy for the visible light
      photocatalysis and solar energy conversion. Based on the optimized structures of
      X-doped TiO(2), the defect formation energies and the density of states were
      calculated to analyze the energetic properties, band edges, and the band gap
      states. Our calculated results show that dopants substituting for Ti is
      energetically unfavorable in the order Si < Sn < Ge < Pb under both O-rich and Ti
      rich growth conditions. The electronic structures show that there is a reduction
      of band gap about 0.1 approximately 0.55 eV in X-doped rutile TiO(2). Si- and Ge
      doped anatase TiO(2) also decrease by 0.20 and 0.15 eV, but broadening by 0.06
      and 0.02 eV occurs in Sn- and Pb-doped systems. The calculated results explain
      the experimental observations. Furthermore, it can be predicted that Ge-doped
      TiO(2) can be active for overall water splitting under visible light photons
      whereas Si-, Sn-, and Pb-doped TiO(2) are only suitable for photo-oxidation.

PMID- 19756273
TI  - Coupled mutual diffusion in solutions of micelles and solubilizates.
AB  - The coupled diffusion of micelles and solubilizates has been studied by measuring
      ternary mutual diffusion coefficients (D(ik)) for aqueous solutions of
      dodecylsulfobetaine (SB12) with added butanol, pentanol, or hexanol. SB12
      micelles solubilize alcohols, so diffusing SB12(1) might be expected to co
      transport alcohol(2). Negative values of cross-coefficient D(21) indicate,
      however, that the diffusion of SB12 drives substantial counterflows of alcohol.
      To help interpret the results, measured decreases in critical micelle
      concentrations with added alcohol (ROH) are used to evaluate equilibrium
      constants for the formation of (SB12)(m)(ROH)(n) mixed micelles. Increasing the
      concentration of SB12 along a diffusion path raises the concentrations of
      micelles and solubilized alcohol while lowering the concentration of free
      alcohol. The resulting flux of relatively mobile free alcohol molecules up SB12
      concentration gradients is larger than the flux of solubilized alcohol down SB12
      gradients, producing net countercurrent coupled fluxes of alcohol. The measured
      D(ik) coefficients are in close agreement (+/- 0.05 x 10(-5) cm(2) s(-1)) with
      predictions using self-diffusion coefficients (D(i)*) for SB12 and alcohol in
      solutions at thermodynamic equilibrium and the relations D(ik) = partial
      differential(C(i)D(i)*)/ partial differentialC(k) proposed recently for mutual
      diffusion in non-equilibrium solutions of associating solutes. Mutual diffusion
      coefficients for coupled surfactant-solubilizate diffusion are used to evaluate
      equilibrium constants for the formation of surfactant-solubilizate mixed
      micelles.

PMID- 19756274
TI  - Appraising the relative strengths of C-H***O[double bond, length as m-dash]C and
      N-H***O[double bond, length as m-dash]C interactions from cis-N-methylacetamide
      multimers.
AB  - The strength of C-H***O[double bond, length as m-dash]C interactions relative to
      regular N-H***O[double bond, length as m-dash]C hydrogen bonds is estimated from
      DFT quantum calculations on multimers of cis-N-methylacetamide (NMA). Assuming
      transferable hydrogen-bond increments, treatment of various constraint-free NMA
      dimers and trimers enables us to provide statistical values for (i) the direct
      energy difference between the two kinds of interaction (calculated around 5 kcal
      mol(-1)), and (ii) their associated binding energies, hence the ratio of their
      strengths. Combining the binding energies with other critically-analyzed
      observables, a relative strength of about 20%-say no more than one fifth-is
      finally proposed.

PMID- 19756275
TI  - Repair of O6-methylguanine to guanine by cysteine in the absence and presence of
      histidine and by cysteine thiolate anion: a quantum chemical study.
AB  - O6-methylguanine (O6mG) is known to be a potential mutagenic modification of
      guanine as it mispairs with thymine in DNA and causes GC to AT transversion
      mutation. It is experimentally known that O6mG can be repaired to guanine by the
      protein O6-alkylguanine-DNA alkyltransferase (AGT), a cysteine residue being the
      main active site. In the present work, the mechanisms of repair of cis-O6
      methylguanine (O6mG) to guanine due to its reaction with cysteine in the absence
      and presence of histidine and with cysteine thiolate anion were investigated
      theoretically using the B3LYP hybrid functional of density functional theory and
      the second order Moller-Plesset perturbation (MP2) theory. Reactant, intermediate
      and product complexes as well as transition states involved in these reactions
      were fully optimized at the B3LYP/6-31 + G* level of theory in the gas phase. The
      solvent effect of water was treated using the polarizable continuum model (PCM).
      Single point energy calculations were performed at the B3LYP/AUG-cc-pVDZ and
      MP2/6-31 + G* levels of theory in the gas phase and aqueous media. It is found
      that cysteine alone can repair the cis-O6mG to guanine, but the involvement of
      histidine along with cysteine lowers down the barrier energy significantly.
      However, when cysteine thiolate anion is used in place of cysteine, the barrier
      energy is strongly reduced. These results broadly support the suggestions based
      on experimental studies.

PMID- 19756276
TI  - Chaos in the classical mechanics of bound and quasi-bound HX-4He complexes with X
      = F, Cl, Br, CN.
AB  - The classical dynamics of weakly bound floppy van der Waals complexes have been
      extensively studied in the past except for the weakest of all, i.e., those
      involving He atoms. These complexes are of considerable current interest in light
      of recent experimental work focussed on the study of molecules trapped in small
      droplets of the quantum solvent (4)He. Despite a number of quantum
      investigations, details on the dynamics of how quantum solvation occurs remain
      unclear. In this paper, the classical rotational dynamics of a series of van der
      Waals complexes, HX-(4)He with X = F, Cl, Br, CN, are studied. In all cases, the
      ground state dynamics are found to be almost entirely chaotic, in sharp contrast
      to other floppy complexes, such as HCl-Ar, for which chaos sets in only at
      relatively high energies. The consequences of this result for quantum solvation
      are discussed. We also investigate rotationally excited states with J = 1 which,
      except for HCN-(4)He, are actually resonances that decay by rotational pre
      dissociation.

PMID- 19756277
TI  - A comparison of infrared spectroscopic methods for the study of heterogeneous
      reactions occurring on atmospheric aerosol proxies.
AB  - In this paper, the heterogeneous reaction between oleic acid and ozone has been
      studied using infrared spectroscopy in two distinctly different experimental
      configurations. The effect of the experiment on the observed products and rates
      of reaction is compared in order to derive a better understanding of some of the
      variations in oleic acid reaction rates reported by a range of researchers. One
      set of measurements is made using thin films of oleic acid in an attenuated total
      internal reflection configuration, and it is shown that a treatment in which the
      ATR evanescent wave is convolved with a moving reaction front is essential for
      the extraction of reliable kinetic data. The results are compared to similar
      measurements in a recently developed aerosol flow tube equipped with a cross-beam
      infrared spectroscopic probe. Rates of reaction in the aerosol phase are observed
      to be approximately 10 times faster and possible reasons for this discussed.

PMID- 19756278
TI  - Co oxidation accompanied by degradation of Pt-Co alloy cathode catalysts in
      polymer electrolyte fuel cells.
AB  - The electronic structure of Co ions in Pt(3)Co alloy cathode catalysts for
      polymer electrolyte fuel cells (PEFCs) under different operation conditions has
      been investigated using X-ray absorption spectroscopy (XAS). The line shapes of
      the Co 2p XAS spectra indicate that the Co atoms in the cathode layer are
      predominantly metallic in all cells, and the spectrum of the first-operated cell
      is the most metallic among them. The Co 2p XAS spectra slightly change depending
      on the operation conditions, and the differences in the spectra can be explained
      by the presence of cobalt oxides. Decomposition analysis of the Co 2p XAS spectra
      reveals that the operation of Pt-Co PEFCs yields trivalently oxidised cobalt in
      the cathode layer.

PMID- 19756279
TI  - A volcano curve: optimizing methanol electro-oxidation on Pt-decorated Ru
      nanoparticles.
AB  - Controlled Pt adlayers were deposited on commercial Ru nanoparticles (NPs) using
      an industrially scalable one-pot ethylene glycol (EG) reduction based method and
      were characterized by X-ray diffraction (XRD), electrochemical (EC) CO stripping
      voltammetry, inductively-coupled plasma optical emission spectrometry (ICP-OES),
      X-ray photoemission spectroscopy (XPS), and transmission electron microscopy
      (TEM). Compared with the previously used "spontaneous deposition", the wet
      chemistry-based EG method is less technically demanding, i.e. no need to handle
      high-temperature hydrogen reduction, offers a better control of the Pt packing
      density (PD), enables the formation of stable, segregated Pt surface adlayers for
      optimal tuning and use of Pt, and effectively prevents NPs sintering. Two batches
      of a total of 11 (8 vs. 3) samples with different values of Pt PD ranging from
      0.05 to 0.93 were prepared, with a time interval of more than 18 months between
      the sytheses of the two batches of samples, and an excellent reproducibility of
      results was observed. All samples were investigated in terms of methanol (MeOH)
      electro-oxidation (EO) by cyclic voltammetry (CV) and chronoamperometry (CA).
      Although the peak current of CV increased as the Pt content increased, the long
      term steady-state MeOH electro-oxidation current density of the Pt-decorated Ru
      NPs measured by CA showed a volcano curve as a function of the Pt PD, with the
      maximum appearing at the PD of 0.31. The optimal peak activity was approximately
      150% higher than that of the industrial benchmark PtRu (1 : 1) alloy NPs and
      could deliver the same performance at half the electrode material cost.
      Fundamentally, such a volcano curve in the reaction current is the result of two
      competing processes of the EO of MeOH: the triple dehydrogenation of MeOH that
      prefers more Pt ensemble sites, and the elimination of poisonous CO that is
      enhanced by more adjacent Ru/Pt sites via the so-called bifunctional mechanism
      and also by possible electronic effects at low Pt coverages.

PMID- 19756280
TI  - Electron attachment to trinitrotoluene (TNT) embedded in He droplets: complete
      freezing of dissociation intermediates in an extended range of electron energies.
AB  - Electron attachment to the explosive trinitrotoluene (TNT) embedded in Helium
      droplets (TNT@He) generates the non-decomposed complexes (TNT)(n)(-), but no
      fragment ions in the entire energy range 0-12 eV. This strongly contrasts the
      behavior of single TNT molecules in the gas phase at ambient temperatures, where
      electron capture leads to a variety of different fragmentation products via
      different dissociative electron attachment (DEA) reactions. Single TNT molecules
      decompose by attachment of an electron at virtually no extra energy reflecting
      the explosive nature of the compound. The complete freezing of dissociation
      intermediates in TNT embedded in the droplet is explained by the particular
      mechanisms of DEA in nitrobenzenes, which is characterized by complex
      rearrangement processes in the transient negative ion (TNI) prior to
      decomposition. These mechanisms provide the condition for effective energy
      withdrawal from the TNI into the dissipative environment thereby completely
      suppressing its decomposition.

PMID- 19756281
TI  - Efficiency of the NICSzz-scan curves to probe the antiaromaticity of organic and
      inorganic rings/cages.
AB  - In the present study it was demonstrated that the NICS(zz)-scan patterns along
      with symmetry-based selection rules can unequivocally probe the antiaromaticity
      in a wide range of antiaromatic organic and inorganic rings/cages. The NICS(zz)
      scan profiles typical of antiaromaticity correspond to symmetric curves around
      the axis perpendicular to the ring plane with the positive NICS(zz)(R) values
      decaying rapidly and monotonically with respect to the distance R from the ring
      center. The magnitude of the induced paratropic ring currents is determined by
      the magnitude of the excitation energies of the rotationally (R(z)) allowed HOMO 
      -> LUMO transitions. The appearance of the NICS(zz)-scan curves in conjunction
      with the symmetry-based selection rules constitute a powerful magnetic criterion
      of antiaromaticity capable of predicting the antiaromaticity in the realm of
      antiaromatic organic, inorganic and "all-metal" molecules lifting up all
      controversies with respect to the aromaticity/antiaromaticity for some peculiar
      aromatic/antiaromatic molecules.

PMID- 19756282
TI  - Photochemical deactivation pathways of the A-state allyl radical.
AB  - Ab initio direct molecular dynamics with trajectory surface hopping methods
      simulates the photochemical deactivation pathways of the allyl radical, C(3)H(5),
      following electronic excitation to the A-state. The electronically nonadiabatic
      dynamics mediated by two conical intersections produces predominantly hot ground
      state allyl radicals along both the disrotatory and conrotatory photochemical
      deactivation pathways with a near synchronous rotation of the terminal methylene
      groups. The electrocyclic transformation of the allyl radical to the cyclopropyl
      radical is a minor channel accounting for 8% of all trajectories with 98% of them
      following the disrotatory pathway.

PMID- 19756283
TI  - DFT calculations of the EPR parameters for Cu(ii) DETA imidazole complexes.
AB  - The electron paramagnetic resonance (EPR) parameters for Cu(ii)
      diethylenetriamine imidazole complexes, which serve as empirical models for
      copper-containing proteins, were calculated using density functional theory
      (DFT). The orientations of three different types of imidazole ligands, imidazole,
      1-methylimidazole and 4-methylimidazole, were investigated by rotating the ligand
      about the Cu(ii) imidazole bond. The calculated EPR values indicate that the
      imidazole ligands studied are oriented approximately +/-45 degrees with respect
      to the ligand plane. EPR parameters calculated using the B3LYP density functional
      in conjunction with the conductor-like solvent model (COSMO) show the best
      agreement with the experimentally determined EPR values. Good agreement with
      electron spin echo envelope modulation (ESEEM) data is achieved when an explicit
      water molecule is located near the remote nitrogen atom of the imidazole ligand.
      The implications of these DFT calculations for interpreting experimental pulsed
      EPR data for copper proteins containing imidazole ligands are discussed.

PMID- 19756284
TI  - The use of nanometer-sized hydrographene species for support material for fuel
      cell electrode catalysts: a theoretical proposal.
AB  - Density functional theory (DFT) calculations propose that nanometer-sized
      hydrographene species, graphene-based clusters terminated by H atoms are a
      promising candidate for a support material for Pt catalysts in fuel cell. The
      proposal is based on the following three criteria: a small HOMO-LUMO gap of a
      nanometer-sized hydrographene species with and without a Pt cluster being
      comparable to zero-gap in infinite-size graphene, strengthening interactions of a
      Pt cluster with hydrographene species by utilizing its edge, and spontaneous H(2)
      activation by a Pt cluster on a carbon surface.

PMID- 19756285
TI  - Micro-solvation of the Zn2+ ion-a case study.
AB  - The structures and thermodynamic parameters of hydrated zinc ion clusters
      incorporating a single zinc ion and up to eighteen water molecules have been
      determined with a quantum mechanical hybrid density functional, namely B3LYP
      using cc-PVDZ basis functions for H and O and a split valence 6-31G (d, p) basis
      function for Zn. The geometries for all the zinc ion water clusters are optimized
      with several initial guess structures and without imposing any initial symmetry
      restriction. Zinc metal ion is found to be preferably four coordinated for
      smaller sizes of hydrated cluster but attains an octahedral coordination for
      larger sizes (n >or= 11) of hydrated cluster. Structures with seven or more than
      seven water molecules attached directly to the central zinc ion are not found.
      The calculated gas phase coordination number in the first solvation sphere of a
      large hydrated zinc metal ion is found to be six and the same is also confirmed
      in the force field based classical molecular dynamics simulation study for an
      aqueous zinc ion and thus confirms the experimental findings. The equilibrium
      zinc-oxygen distance of 2.09328 A at the present B3LYP level of study is in
      excellent agreement with the X-ray diffraction result of 2.093 +/- 0.002 A for a
      hexahydrated zinc cluster.

PMID- 19756286
TI  - XPS study of nitrogen dioxide adsorption on metal oxide particle surfaces under
      different environmental conditions.
AB  - The adsorption of nitrogen dioxide on gamma aluminium oxide (gamma-Al(2)O(3)) and
      alpha iron oxide (alpha-Fe(2)O(3)) particle surfaces under various conditions of
      relative humidity, presence of molecular oxygen and UV light has been
      investigated. X-Ray photoelectron spectroscopy (XPS) is used to monitor the
      different surface species that form under these environmental conditions.
      Adsorption of NO(2) on aluminum oxide particle surfaces results primarily in the
      formation of surface nitrate, NO(3)(-) with an oxidation state of +5, as
      indicated by a peak with binding energy of 407.3 eV in the N1s region. An
      additional minority species, sensitive to the presence of relative humidity and
      molecular oxygen, is also observed in the N1s region with lower binding energy of
      405.9 eV. This peak is assigned to a surface species in the +4 oxidation state.
      When irradiated with UV light, other species form on the surface. These surface
      bound photochemical products all have lower binding energy, between 400 and 402
      eV, indicating reduced nitrogen species in the range of N oxidations states
      spanning +1 to -1. Co-adsorbed water decreases the amount of these reduced
      surface-bound products while the presence of molecular oxygen completely
      suppresses the formation of all reduced nitrogen species on aluminum oxide
      particle surfaces. For NO(2) on iron oxide particle surfaces, photoreduction is
      enhanced relative to gamma-Al(2)O(3) and surface bound photoreduced species are
      observed under all environmental conditions. Complementing the experimental data,
      N1s core electron binding energies (CEBEs) were calculated using DFT for a number
      of nitrogen-containing species in the gas phase and adsorbed on an Al(8)O(12)
      cluster. A range of CEBEs is calculated for various nitrogen species in different
      adsorption modes and oxidation states. These calculated values are discussed in
      light of the peaks observed in the XPS N1s region and the possible species that
      form following NO(2) adsorption and photoreaction on metal oxide particle
      surfaces under different conditions of relative humidity, presence of molecular
      oxygen and UV light.

PMID- 19756287
TI  - A comprehensive decomposition analysis of stabilization energy (CDASE) and its
      application in locating the rate-determining step of multi-step reactions.
AB  - Stabilization energy, as proposed by Parr and Pearson (J. Am. Chem. Soc., 1983,
      105, 7512) is decomposed into fragments. When the donor is not a perfect one and
      both the donor and the acceptor are ordinary organic molecules this decomposition
      is shown to provide energy fragments which, individually, can be correlated to
      the reaction rate of that particular step. It is shown how these different energy
      fragments can be used, together with the global electrophilicity value of the
      acceptor (w(A)), to locate the rate-determining step in multi-step reactions.

PMID- 19756288
TI  - Jet-cooled vibronic spectroscopy of potential intermediates along the pathway to
      PAH: phenylcyclopenta-1,3-diene.
AB  - The vibronic excitation spectrum of phenylcyclopenta-1,3-diene (PCP3D) has been
      recorded in a supersonic expansion using resonant-two-photon ionization (R2PI)
      and laser-induced fluorescence (LIF) techniques. The spectrum is dominated by the
      S(0)-S(1) origin transition (31,739 cm(-1)), with several low-frequency vibronic
      bands in the first 400 cm(-1), followed by a sharp cut-off in intensity due to
      turn-on of a non-radiative process. Single vibronic level fluorescence (SVLF)
      spectra were recorded for the S(1) origin and several vibronic bands of PCP3D.
      The excitation and emission spectra show that the molecule is planar with C(s)
      symmetry in both the ground and excited states. Torsional potentials were
      simulated from the observed torsional structure in the excitation and emission
      spectra. The S(0) potential (V(2) = 1237 cm(-1), V(4) = -256 cm(-1)) is
      associated with a flat-bottomed potential supporting large inter-ring angular
      changes with little cost in energy (+/-36 degrees at 200 cm(-1)), with a barrier
      of 1237 cm(-1) at the perpendicular geometry. The S(1) potential is much stiffer
      about the planar geometry, with a calculated barrier five times larger than in
      S(0) (V(2) = 6732 cm(-1), V(4) = -477 cm(-1)). Based on the torsional
      assignments, weak bands in the same frequency region assigned earlier to the
      structural isomer phenylcyclopenta-1,4-diene [J. J. Newby, J. A. Stearns, C. P.
      Liu and T. S. Zwier, J. Phys. Chem. A, 2007, 111, 10914-10927] have been re
      assigned as hot bands arising from v'' = 1 in the inter-ring torsion, nu(57).

PMID- 19756289
TI  - Jet-cooled vibronic spectroscopy and asymmetric torsional potentials of
      phenylcyclopentene.
AB  - The ultraviolet spectroscopy of the S(1) <-- S(0) transition of 1
      phenylcyclopentene (PCP) was studied by resonant-two-photon ionization (R2PI),
      laser-induced fluorescence (LIF) and single vibronic level fluorescence (SVLF).
      UV-UV hole-burning (UVHB) spectroscopy was used to determine that there is only
      one spectroscopically distinct conformer in the supersonic expansion. The
      excitation spectrum shows extensive vibronic structure extending to over 1000 cm(
      1) above the electronic origin (34,646 cm(-1)). Much of the vibronic structure is
      similar to that of styrene and other singly substituted benzene derivatives, with
      Franck-Condon (FC) activity predominantly in substituent-sensitive benzene modes.
      Sizeable FC progressions were also found in the inter-ring torsion, reflecting a
      large displacement in the inter-ring angle upon electronic excitation. No
      evidence for FC activity in the ring-puckering coordinate is observed. The
      torsional potentials of the ground and excited states were determined from the
      experimental transition frequencies by fitting the calculated to the experimental
      torsional frequency spacings in an automated least-squares fitting procedure. The
      S(1) torsional potential is a symmetric single-well potential centered around a
      locally planar equilibrium geometry at a torsional angle of varphi = 0 degrees .
      The energy levels are reproduced by a cosine term potential function with
      torsional parameters V(2) = 3765 cm(-1) and V(4) = -183 cm(-1). The S(0)
      torsional potential possesses a twisted equilibrium geometry that is strongly
      asymmetric about varphi = 0 degrees due to the non-planarity of the cyclopentene
      ring. The best-fit potential parameters uses a sin/cos potential function
      (odd/even), with V = 948 cm(-1), V = -195 cm(-1), V = -162 cm(-1) and V = -268
      cm(-1). The shape of the potentials are similar to those predicted by relaxed
      potential energy scans calculated at the DFT, CIS and TDDFT//CIS levels of
      theory. The change in the torsional angle varphi upon electronic excitation was
      determined to be approximately 15 degrees from fits of the displacement delta of
      the S(0) torsional potential with respect to the S(1) potential. The simulated
      shift of the S(0) potential with respect to the S(1) potential of approximately
      15 degrees is in very good agreement with that obtained from B3LYP calculations.

PMID- 19756290
TI  - Aggregation of antitumoral drug emodin on Ag nanoparticles: SEF, SERS and
      fluorescence lifetime experiments.
AB  - We have studied the fluorescence and Raman emission of the anthraquinone drug
      emodin immobilized molecules on nanostructured silver surfaces, prepared through
      two different methods. Two different pHs (pH = 10 and pH = 6) have been used. The
      dye aggregation favors SEF at pH = 6, whereas quenching of fluorescence is
      observed at pH = 10, due to the short distance between emodin and Ag particles.
      Along with these results, SERS spectra have given us information about the
      different species present in the solution. We have used two different reducing
      agents to obtain the Ag nanoparticles: hydroxylamine hydrochloride and sodium
      citrate. In all the cases analysed, the enhancement of both SEF and SERS spectra,
      is larger for hydroxylamine hydrochloride than that for sodium citrate. We have
      also measured fluorescence lifetime, observing a shorter lifetime for emodin
      molecules near Ag nanoparticles than that for emodin solved in pure water, thus
      corroborating the results obtained in fluorescence emission spectra.

PMID- 19756291
TI  - Geometrically asymmetric electrodes for probing electrochemical reaction
      kinetics: a case study of hydrogen at the Pt-CsH2PO4 interface.
AB  - Electrochemical reactions can exhibit considerable asymmetry, with the
      polarization behavior of oxidation at a given metal|electrolyte interface
      differing substantially from that of reduction. The reference-less, microcontact
      electrode geometry, in which the electrode overpotentials are geometrically
      constrained to the working electrode (by limiting its area) is experimentally
      convenient, particularly for fuel cell studies, because the results do not rely
      on accurate placement of a reference electrode nor must oxidant and reductant
      gases be sealed off from one another. Here, the conditions under which the
      critical assumption of this geometry applies-that the overpotential at the large
      area counter electrode can be ignored-is numerically assessed. It is found that,
      for cells of sufficiently large area, the effective radius of the counter
      electrode (which defines the area through which the majority of the current
      passes) can be expressed directly as a function of electrolyte thickness and the
      materials properties, sigma, the conductivity of the electrolyte, and k, the
      reaction rate constant for the electrochemical reaction at zero-bias. From this
      effective radius and the true radius of the working electrode, the fraction of
      electrode overpotential at the latter, defined as the extent of isolation, can be
      readily computed. Experimental studies of hydrogen electro-oxidation/proton
      electro-reduction at the Pt|CsH(2)PO(4) interface using two cells of differing
      dimensions both validate the computational results and demonstrate that asymmetry
      in such reactions are readily revealed in the micro-electrode, reference-less
      geometry. The study furthermore confirms the insensitivity of the results to the
      precise placement of the working electrode, while indicating the importance of
      very high isolation values (>99%) to ensure that overpotential contributions of
      the counter electrode do not influence the measurements, particularly as bias is
      increased.

PMID- 19756292
TI  - The formation of colloidal copper nanoparticles stabilized by zinc stearate: one
      pot single-step synthesis and characterization of the core-shell particles.
AB  - A highly efficient one-step process to generate Cu-Zn colloids was developed, in
      which the colloidal particles were synthesized from Cu and Zn stearates by
      reduction with H(2) in a continuously operated stirred tank reactor. The
      resulting spherical, well separated particles have a size of 5-10 nm, consisting
      of a crystalline Cu(0) core (fcc) stabilized by a Zn stearate shell without long
      range order. In situ attenuated total reflection FTIR spectroscopy was used to
      monitor the shift of the C-O stretching vibration of adsorbed CO as a function of
      temperature and pressure. The absence of the CO rotation-vibration bands of
      dissolved CO allowed us to obtain FTIR spectra at a CO pressure of 1.0 MPa at 473
      K resulting in three shifted CO bands at 2030-2025, 1979-1978, and 1920 cm(-1).
      These bands indicate the presence of reduced coadsorbed Zn species on the
      metallic Cu surface. Cyclic CO adsorption experiments demonstrated the dynamics
      of the interaction between the Cu core and the Zn stearate shell.

PMID- 19756293
TI  - Simple method for the rapid simultaneous screening of photocatalytic activity
      over multiple positions of self-cleaning films.
AB  - An intelligent ink, previously shown to be capable of rapidly assessing
      photocatalytic activity, was simply applied via a felt-pen onto a commercially
      available piece of Activ self-cleaning glass. The ink, comprising of redox dye
      resazurin and the sacrificial electron donor glycerol within an aqueous hydroxy
      ethyl cellulose (HEC) polymer media, was photocatalytically degraded in a two
      step process. The key initial stage was the photo-reductive conversion of
      resazurin to resorufin, whereby a colour change from blue to pink occurred. The
      latter stage was the subsequent photo-reduction of the resorufin, where a slower
      change from pink to colourless was seen. Red and green components of red-green
      blue colour extracted from flat-bed scanner digital images of resazurin ink
      coated photocatalytic films at intervals during the photocatalysis reaction were
      inversely proportional to the changes seen via UV-visible absorption spectroscopy
      and indicative of reaction kinetics. A 3 x 3 grid of intelligent ink was drawn
      onto a piece of Activ and a glass blank. The photocatalysis reaction was
      monitored solely by flat-bed digital scanning. Red-green-blue values of
      respective positions on the grid were extracted using a custom-built program
      entitled RGB Extractor. The program was capable of extracting a number of 5 x 5
      pixel averages of red-green-blue components simultaneously. Allocation of merely
      three coordinates allowed for the automatic generation of a grid, with scroll
      bars controlling the number of positions to be extracted on the grid formed. No
      significant change in red and green components for any position on the glass
      blank was observed; however, the Activ film displayed a homogenous photo
      reduction of the dye, reaching maxima in red and minima in green components in 23
      +/- 3 and 14 +/- 2 min, respectively. A compositionally graded N-doped titania
      film synthesised in house via a combinatorial APCVD reaction was also
      photocatalytically tested by this method where 247 positions on a 13 x 19 grid
      were simultaneously analysed. The dramatic variation in photocatalysis observed
      was rapidly quantified for all positions (2-3 hours) allowing for correlations to
      be made between thicknesses and N : Ti% compositions attained from Swanepoel and
      WDX analysis, respectively. N incorporation within this system was found to be
      detrimental to film activity for the photocatalysis reaction of intelligent ink
      under 365 nm light.

PMID- 19756298
TI  - The repertoire of glycan determinants in the human glycome.
AB  - The number of glycan determinants that comprise the human glycome is not known.
      This uncertainty arises from limited knowledge of the total number of distinct
      glycans and glycan structures in the human glycome, as well as limited
      information about the glycan determinants recognized by glycan-binding proteins
      (GBPs), which include lectins, receptors, toxins, microbial adhesins, antibodies,
      and enzymes. Available evidence indicates that GBP binding sites may accommodate
      glycan determinants made up of 2 to 6 linear monosaccharides, together with their
      potential side chains containing other sugars and modifications, such as
      sulfation, phosphorylation, and acetylation. Glycosaminoglycans, including
      heparin and heparan sulfate, comprise repeating disaccharide motifs, where a
      linear sequence of 5 to 6 monosaccharides may be required for recognition. Based
      on our current knowledge of the composition of the glycome and the size of GBP
      binding sites, glycoproteins and glycolipids may contain approximately 3000
      glycan determinants with an additional approximately 4000 theoretical
      pentasaccharide sequences in glycosaminoglycans. These numbers provide an
      achievable target for new chemical and/or enzymatic syntheses, and raise new
      challenges for defining the total glycome and the determinants recognized by
      GBPs.

PMID- 19756299
TI  - Understanding apoptosis by systems biology approaches.
AB  - Apoptosis is a process common to all multicellular organisms. Apoptosis leads to
      the elimination of cells via a complex but highly defined cellular programme.
      Defects in the regulation of apoptosis result in serious diseases such as cancer,
      autoimmunity, AIDS and neurodegeneration. Recently, a substantial step forward in
      understanding the complex apoptotic pathways has been made by utilising systems
      biology approaches. Systems biology combines rigorous mathematical modelling with
      experimental approaches in a closed loop cycle for advancing our knowledge about
      complex biological processes. In this review we describe the contemporary systems
      biology studies devoted to apoptotic signalling and focus on the question of how
      systems biology helps to understand life/death decisions made in the cell and to
      develop new approaches to rational treatment strategies.

PMID- 19756300
TI  - Receptor tyrosine kinase signaling: a view from quantitative proteomics.
AB  - Growth factor receptor signaling via receptor tyrosine kinases (RTKs) is one of
      the basic cellular communication principals found in all metazoans. Extracellular
      signals are transferred via membrane spanning receptors into the cytoplasm,
      reversible tyrosine phosphorylation being the hallmark of all RTKs. In recent
      years proteomic approaches have yielded detailed descriptions of cellular
      signaling events. Quantitative proteomics is able to characterize the exact
      position and strength of post-translational modifications (PTMs) providing
      essential information for understanding the molecular basis of signal
      transduction. Numerous new post-translational modification sites have been
      identified by quantitative mass spectrometry-based proteomics. In addition,
      plentiful new players in signal transduction have been identified underlining the
      complexity and the modular architecture of most signaling networks. In this
      review, we outline the principles of signal transduction via RTKs and highlight
      some of the new insights obtained from proteomic approaches such as protein
      microarrays and quantitative mass spectrometry.

PMID- 19756301
TI  - Phosphoproteomics--finally fulfilling the promise?
AB  - Networks of protein-protein and protein-metabolite interactions are commonly
      found in biological systems where signals must be passed from one location or
      component within a cell to another, such as from a receptor on the plasma
      membrane to a transcription factor in the nucleus. Regulation of such networks,
      or signal transduction pathways, is often achieved by transient, reversible
      modification of the components involved. Several types of post-translational
      modifications of proteins are employed in signal transduction including
      ubiquitylation of lysines and palmitoylation of cysteines, but by far the best
      appreciated and apparently the most important involves phosphorylation of serine,
      threonine and tyrosine residues. Whilst protein phosphorylation has long been
      recognized as functionally important, low stoichiometry has ultimately impeded
      global analyses (phosphoproteomics). Recent developments in the application of
      metal oxide chromatography and advanced mass spectrometric techniques have
      enabled phosphoproteomics to move beyond mere proof-of-principle experiments, to
      the stage where it can successfully address complex biological questions. Here we
      cover the development of phosphopeptide/protein analysis by mass spectrometry and
      the various techniques used to enrich phosphopeptides/proteins. We also speculate
      on the future of phosphoproteomic research, now that the goal of generating
      global phosphoproteomic datasets has been realized.

PMID- 19756302
TI  - Mitochondrial proteomics and its application in biomedical research.
AB  - Mitochondria are essential organelles that play key roles in a number of cellular
      processes. Therefore, it is not surprising that DNA mutations and mitochondrial
      protein dysfunctions have been associated with several diseases, aging and
      tumorigenic processes. To date, proteomic strategies have increased our knowledge
      about the functions of mitochondrial proteins. The use of proteomics technology
      will be essential to expand the analysis of mitochondrial protein dysfunctions
      and their pathogenic features. This review will focus on the state-of-art
      proteomic strategies in mitochondrial research, and their application to
      biomedicine.

PMID- 19756303
TI  - Fluorine--a new element in the design of membrane-active peptides.
AB  - Antimicrobial peptides (also known as genetically encoded peptide antibiotics)
      are a diverse class of short cationic amphipathic polypeptides that exhibit a
      broad-spectrum of antimicrobial activities by selectively disrupting the
      bacterial cell membrane. In this review article, we present the use of
      fluorinated amino acids in the design of antimicrobial peptides and other
      membrane-active peptides.

PMID- 19756304
TI  - Antibacterial activity and cytotoxicity of PEGylated poly(amidoamine) dendrimers.
AB  - We have investigated the antibacterial activity and cytotoxicity of a series of
      amino-terminated poly(amidoamine) (PAMAM) dendrimers modified with poly(ethylene
      glycol) (PEG) groups. The antibacterial activity of the PAMAM dendrimers and
      their derivatives against the common ocular pathogens, Pseudomonas aeruginosa and
      Staphylococcus aureus, was evaluated by their minimum inhibitory concentrations
      (MICs). For the unmodified third and fifth generation (G3 and G5) amino
      terminated dendrimers, the MICs against both P. aeruginosa and S. aureus were in
      the range of 6.3-12.5 microg mL(-1), comparable to that of the antimicrobial
      peptide LL-37 (1.3-12.5 microg mL(-1)) and within the wide range of 0.047-128
      microg mL(-1) for the fluoroquinolone antibiotics. PEGylation of the dendrimers
      decreased their antibacterial activities, especially for the Gram-positive
      bacteria (S. aureus). The reduction in potency is likely due to the decrease in
      the number of protonated amino groups and shielding of the positive charges by
      the PEG chains, thus decreasing the electrostatic interactions of the dendrimers
      with the negatively-charged bacterial surface. Interestingly, localization of a
      greater number of amino groups on G5 vs. G3 dendrimers did not improve the
      potency. Significantly, even a low degree of PEGylation, e.g. 6% with EG(11) on
      G3 dendrimer, greatly reduced the cytotoxicity towards human corneal epithelial
      cells while maintaining a high potency against P. aeruginosa. The cytotoxicity of
      the PEGylated dendrimers to host cells is much lower than that reported for
      antimicrobial peptides. Furthermore, the MICs of these dendrimers against P.
      aeruginosa are more than two orders of magnitude lower than other antimicrobial
      polymers reported to date. These results motivate further exploration of the
      potential of cationic dendrimers as a new class of antimicrobial agents that may
      be less likely to induce bacterial resistance than standard antibiotics.

PMID- 19756305
TI  - Zinc-activated C-peptide resistance to the type 2 diabetic erythrocyte is
      associated with hyperglycemia-induced phosphatidylserine externalization and
      reversed by metformin.
AB  - Insulin resistance can broadly be defined as the diminished ability of cells to
      respond to the action of insulin in transporting glucose from the bloodstream
      into cells and tissues. Here, we report that erythrocytes (ERYs) obtained from
      type 2 diabetic rats display an apparent resistance to Zn(2+)-activated C
      peptide. Thus, the aims of this study were to demonstrate that Zn(2+)-activated C
      peptide exerts potentially beneficial effects on healthy ERYs and that these same
      effects on type 2 diabetic ERYs are enhanced in the presence of metformin.
      Incubation of ERYs (obtained from type 2 diabetic BBZDR/Wor-rats) with Zn(2+)
      activated C-peptide followed by chemiluminescence measurements of ATP resulted in
      a 31.2 +/- 4.0% increase in ATP release from these ERYs compared to a 78.4 +/-
      4.9% increase from control ERYs. Glucose accumulation in diabetic ERYs, measured
      by scintillation counting of (14)C-labeled glucose, increased by 35.8 +/- 1.3% in
      the presence of the Zn(2+)-activated C-peptide, a value significantly lower than
      results obtained from control ERYs (64.3 +/- 5.1%). When Zn(2+)-activated C
      peptide was exogenously added to diabetic ERYs, immunoassays revealed a 32.5 +/-
      8.2% increase in C-peptide absorbance compared to a 64.4 +/- 10.3% increase in
      control ERYs. Phosphatidylserine (PS) externalization and metformin sensitization
      of Zn(2+)-activated C-peptide were examined spectrofluorometrically by measuring
      the binding of FITC-labeled annexin to PS. The incubation of diabetic ERYs with
      metformin prior to the addition of Zn(2+)-activated C-peptide resulted in values
      that were statistically equivalent to those of controls. Summarily, data obtained
      here demonstrate an apparent resistance to Zn(2+)-activated C-peptide by the ERY
      that is corrected by metformin.

PMID- 19756306
TI  - Quantification of the effect of amino acids on an integrated mTOR and insulin
      signaling pathway.
AB  - Integration of nutrient and growth factor signaling pathways through mammalian
      TOR (mTOR) plays a central role in the regulation of cell growth. However, the
      mechanism of integration of these two signals in mTOR activation is largely
      unknown. Moreover, the nutritional input involving amino acids is yet to be
      characterized. Excess amino acid conditions, such as in obesity and protein-rich
      diets, are known to regulate insulin signaling through mTOR activation resulting
      in insulin resistance. Here, we develop a dynamic model to identify the
      regulatory role of amino acids in mTOR activation and to study its effect on
      insulin signaling in relation to multiple feedback loops present in the insulin
      signaling pathway. The analysis revealed that amino acids bring about multiple
      effects in the regulation of mTOR that might be represented by a single
      mechanism. Insulin signaling was demonstrated to operate between two extreme
      conditions involving tumor growth and insulin resistance, with multiple feedback
      loops tightly controlling and maintaining a robust insulin response. The state of
      insulin resistance was characterized by a decrease in the time lag or an increase
      in the magnitude of the negative feedback loop facilitated through perturbations
      such as excess input of amino acids. Such a condition disturbs the delicate
      balance between positive and negative feedback loops to yield an insulin
      resistant state.

PMID- 19756307
TI  - Enhanced levels of mitochondrial enzyme 17beta-hydroxysteroid dehydrogenase type
      10 in patients with Alzheimer disease and multiple sclerosis.
AB  - The multifunctional mitochondrial enzyme 17beta-hydroxysteroid dehydrogenase type
      10 might play a role in the development of Alzheimer disease via its high
      affinity binding to amyloid beta peptides and its neuronal over-expression. It is
      suggested that the cerebrospinal fluid levels of the enzyme, free or bound to
      amyloid beta peptides, are a potential specific biomarker of Alzheimer disease.
      However, mitochondrial dysfunction seems to play a role in many neurological
      diseases including multiple sclerosis. In this study, the specificity of changes
      in relation to the enzyme over-expression was evaluated using enzyme-linked
      immunosorbent and surface plasmon resonance sensors. The data indicated
      pronounced increases in the enzyme levels, specifically to 179% in multiple
      sclerosis and to 573% in Alzheimer disease when compared to the age-matched
      controls. Although the differences between both diseases were statistically
      significant, enzyme levels do not appear to be a highly specific biomarker of
      Alzheimer disease. On the other hand, enhancement in levels of the enzyme bound
      to amyloid beta peptides was only observed in people with Alzheimer disease,
      which suggests that the complex should be further considered as a possible
      biomarker. In patients with multiple sclerosis, our results are the first to
      demonstrate significant changes in enzyme expression and to suggest possible
      alterations in amyloid beta peptides.

PMID- 19756308
TI  - Molecular cloning, sequence analysis and functional characterization of the gene
      cluster for biosynthesis of K-252a and its analogs.
AB  - Among the indolocarbazole alkaloids of antitumor antibiotics, K-252a represents a
      structurally unique indolocarbazole glycoside and exhibits potent neuroprotective
      and broad anticancer activities. K-252a consists of K-252c and the unusual
      dihydrostreptose moiety, linked together with oxidative and glycosidic C-N bonds.
      Herein, we reported a complete sequence of an approximately 45 kb genomic
      fragment harboring the gene cluster for the biosynthesis of indolocarbazole
      alkaloids in Nocardiopsis sp. K-252 (NRRL15532). The sequence of 35 open reading
      frames discovered several new, critical genes, hence shedding new light on
      biosynthesis, resistance and regulation of K-252a and its analogs. To
      functionally characterize the gene cluster in vitro and in enzyme level, a
      multigene expression cassette containing the K-252c biosynthetic genes was
      constructed and successfully overexpressed in Escherichia coli to yield soluble
      proteins for cell-free tandem enzymatic assays. Consequently, the heterologous
      expression with soluble NokA and NokB led to in vitro production of
      chromopyrrolic acid (CPA), thereby providing functional evidence for K-252c
      biosynthesis. Moreover, a facile production of CPA in culture broth was
      successfully accomplished by using an in vivo biotransformation of L-tryptophan
      with E. coli harboring the gene cassette. Importantly, by sequence analysis and
      the functional characterization here and in the companion paper, biosynthetic
      pathways leading to formation of K-252a and its analogs were hence proposed.
      Together, the results provide critical information and materials useful for
      combinatorial biosynthesis of K-252a and its analogs for therapeutic
      applications.

PMID- 19756309
TI  - Biochemical characterization and substrate specificity of the gene cluster for
      biosyntheses of K-252a and its analogs by in vitro heterologous expression system
      of Escherichia coli.
AB  - The indolocarbazole family of natural products has attracted great attention
      because of their unique structural features and potential therapeutic
      applications. Structurally distinct in the family, K-252a is characterized by an
      unusual dihydrostreptose moiety cross-bridged to K-252c aglycone with two C-N
      linkages. K-252a has served as a valuable lead for treatments of various cancers
      and neurodegenerative disorders. Recent cloning of the nok gene cluster for
      biosyntheses of K-252a and its analogs from Nocardiopsis sp. K-252 (NRRL15532)
      has revealed the nokABCD genes indispensible for K-252c biosynthesis and the key
      gene (nokL) coding for N-glycosylation. Herein, we report the first, successful
      demonstration of in vitro sugar transferase activity of indolocarbazole N
      glycosyltransferase (NokL) by use of soluble protein expressed from Escherichia
      coli. Notably, NokL was found to exhibit peculiar mode of substrate promiscuity.
      Moreover, NokA and NokB reactions were biochemically characterized thoroughly by
      natural and alternative (e.g. fluoro-) substrates and by ammonium hydroxide
      (NH(4)OH). Interestingly, the in vitro expression of NokA revealed high substrate
      stereoselectivity, giving several indole-3-pyruvic acid-derived compounds,
      including indol-3-carboxaldehyde (ICA) and indole-3-acetic acid. The use of
      NH(4)OH successfully dissected the in vitro NokA/NokB coupled reaction, revealing
      mechanistic insight into the enzymes and their cross-talking relationship. Also,
      a simple, useful method to synthesize K-252d, ICA and chromopyrrolic acid (the
      NokB product) was developed by the E. coli expression systems of NokL, NokA and
      NokA/NokB, respectively. Together with NokA and NokB, NokL may serve as a useful
      tool for combinatorial engineering of K-252a and its analogs for improved
      therapeutic values.

PMID- 19756310
TI  - Metabonomic characterization of aging and investigation on the anti-aging effects
      of total flavones of Epimedium.
AB  - A liquid chromatography coupled with mass spectrometry (LC/MS) based metabonomics
      approach was applied to characterize the aging of rats, and the anti-aging effect
      of total flavones of Epimedium (TFE), a traditional Chinese medicine, has also
      been investigated. Serum samples collected from 4, 10, 18 and 24 month-old rats
      and TFE-administered rats have been profiled by LC/MS. Thirty age-related
      endogenous metabolites were discovered by partial least squares (PLS) and
      Hotelling's T(2) control chart, among which 25 metabolites were structurally
      identified by MS(n) analysis and ten of them were further confirmed via authentic
      chemicals. All important age-related metabolites, such as unsaturated fatty
      acids, saturated fatty acids, nucleotides, carnosine, ergothioneine and amino
      acids, displayed age-related changes, and most of them were reset to a younger
      level after TFE administration. This study indicated that aging could be
      characterized by changes of lipid metabolisms and accumulation of free radicals.
      The anti-aging effects of TFE might due to the intervention on lipid metabolism
      and its property of anti-oxidation.

PMID- 19756311
TI  - Systems biology meets synthetic biology: a case study of the metabolic effects of
      synthetic rewiring.
AB  - We present a systems biology approach to study the global metabolic effects of
      the insertion of synthetic circuits in a cellular chassis. Our approach combines
      high-throughput proteomics with the MMG probabilistic tool, which integrates the
      data with the metabolic circuit's topology. We present a theoretical analysis of
      the foundations of our approach, as well as experimental results on a mutant
      strain of Escherichia coli where a light-receptor circuit was inserted and
      coupled with lactose metabolism. Our results show that the systems approach
      manages to extract meaningful information from the proteomic data that cannot be
      recovered by naive thresholding of the data. This tool can be used to
      characterise the relationship between new circuits and chassis in synthetic
      biology applications.

PMID- 19756312
TI  - Carbon nanotubes as a protein toxin transporter for selective HER2-positive
      breast cancer cell destruction.
AB  - The recombined ricin A chain protein (RTA) was transported into living cells by
      multiwalled carbon nanotubes (MWNTs) as a cellular carrier, as performed by
      natural ricin B chain protein (RTB). The conjugate of the toxin protein RTA and
      MWNT was found to translocate to the cytoplasm of various cell lines and
      performed biological functions, as evidenced by the induction of cell death. The
      delivery of RTA into the cells via nanotube carriers was directly visualized by
      transmission electron microscopy (TEM) and confocal microscopy. About three times
      higher cell death rates for L-929, HL7702, MCF-7, HeLa and COS-7 cells were
      demonstrated induced by MWNT-RTA conjugates, compared to those achieved by RTA
      alone. Especially for HeLa cells, the cell mortality reached approximately 75%.
      In addition, obvious selective destruction of cancer cells was achieved by
      coupling MWNTs-RTA-HER2, which selectively recognize the HER2/neu receptor on
      certain breast cancer cells. This is the first example of recombined protein
      toxin (RTA)-induced targeting destruction for tumor cells via carbon nanotube
      molecular transporters. The transporting capabilities of carbon nanotubes
      combined with functional proteins may open exciting new venues for drug delivery
      and cancer therapy.

PMID- 19756313
TI  - Network-level analysis of light adaptation in rod cells under normal and altered
      conditions.
AB  - Photoreceptor cells finely adjust their sensitivity and electrical response
      according to changes in light stimuli as a direct consequence of the feedback and
      regulation mechanisms in the phototransduction cascade. In this study, we
      employed a systems biology approach to develop a dynamic model of vertebrate rod
      phototransduction that accounts for the details of the underlying biochemistry.
      Following a bottom-up strategy, we first reproduced the results of a robust model
      developed by Hamer et al. (Vis. Neurosci., 2005, 22(4), 417), and then added a
      number of additional cascade reactions including: (a) explicit reactions to
      simulate the interaction between the activated effector and the regulator of G
      protein signalling (RGS); (b) a reaction for the reformation of the G-protein
      from separate subunits; (c) a reaction for rhodopsin (R) reconstitution from the
      association of the opsin apoprotein with the 11-cis-retinal chromophore; (d)
      reactions for the slow activation of the cascade by opsin. The extended network
      structure successfully reproduced a number of experimental conditions that were
      inaccessible to prior models. With a single set of parameters the model was able
      to predict qualitative and quantitative features of rod photoresponses to light
      stimuli ranging over five orders of magnitude, in normal and altered conditions,
      including genetic manipulations of the cascade components. In particular, the
      model reproduced the salient dynamic features of the rod from Rpe65(-/-) animals,
      a well established model for Leber congenital amaurosis and vitamin A deficiency.
      The results of this study suggest that a systems-level approach can help to
      unravel the adaptation mechanisms in normal and in disease-associated conditions
      on a molecular basis.

PMID- 19756315
TI  - [FT3 value is a possible risk indicator for patients undergoing vascular
      surgery].
AB  - A study on 28 patients undergoing vascular surgery was performed with the aims to
      confirm the postoperative decrease of serum FT3 value, to study the correlation
      between Euthyroid Sick Syndrome (ESS) and postoperative complications, to detect
      a possible correlation between markers of severity of atherosclerosis and ESS. A
      slight but significant decrease in postoperative FT3 value was observed (3.88 +/-
      0.73 vs 3.32 +/- 1.07 p < 0.05), while we could not find any difference in pre
      postoperative FT4 and TSH values. Six patients developed inflammation-related
      complications (Systemic Inflammatory Response Syndrome--SIRS) and they all showed
      a deeper postoperative decrease of FT3 value than non complicated subjects, even
      if the difference was not statistically significant (1st postop day 3.60 +/- 1.05
      vs 2.47 +/- 0.61 p = 0.06). Finally, a strong negative linear correlation was
      observed between preoperative fibrinogen value and FT3 (r = -0.48). FT3 value
      could be a good predictor of risk for inflammatory-related postoperative
      complications. Preoperative FT3 value in patients with atherosclerosis is
      inversely correlated with markers of inflammation activity, mainly with
      fibrinogen.

PMID- 19756316
TI  - [Management of combined psychotherapy and pharmacological treatment. A 'cross
      sectional' study on a selected sample of psychiatrists].
AB  - AIMS: The association between pharmacological treatment and psychotherapy is
      frequent. However doesn't exist any agreement or guide-line about the management
      of this combined therapy. Therefore we considered useful to evaluate which were
      the most frequent way of management of the combined therapy in a sample of 120
      psychiatrists. MATERIALS AND METHODS: A 10-items questionnaire finalized to
      explore the management way of the combined therapy was administered to a sample
      of 120 psychiatrists. A descriptive analysis of the data was made and the
      association between different variables was explored. The statistical analysis
      was performed using SPSS 13.0. RESULTS: 35% of the sample work as a private
      practitioner, 19.17% is involved in public health (CMHT'S). More than 50% of the
      sample consider the combined therapy as a effective. In the public field the
      combined treatment turn out to be the most utilized, opposite than in private
      practice. 75% of the sample manage alone the combined therapy, while 25% work in
      team with a colleague. 85% of the pharmacotherapy is utilized in psychosis with
      positive symptoms, followed by the mood disorder with psychotic symptoms.
      Neuroleptics are the most frequently prescribed drug. CONCLUSIONS: The combined
      therapy seems to be useful when coherently with the psychotherapy theory model.
      The pharmacological treatment should be utilized when strictly necessary and, if
      is possible, the combined therapy should be managed by one psychiatrist.

PMID- 19756317
TI  - Montelparo study: risk factors for age-related macular degeneration in a little
      rural community in Italy.
AB  - PURPOSE: To evaluate the prevalence of age-related maculopathy (ARM) and age
      related macular degeneration (AMD) lesions. Secondary outcome includes to examine
      16 potential risk factors and their prevalence for attribution of risk for ARM
      and AMD in Montelparo, a small, rural and homogeneous population in central
      Italy. MATERIALS AND METHODS: A population aged 65 years old and over underwent a
      detailed interview about demographic notices and possible main risk factors for
      ARM and AMD. The following information were assessed as medical variables with
      bivariate analysis: demographic variables such as age and gender, dietary intake
      (meat, alcohol, fresh and cooked vegetables, fruit and fish), lifestyle factors
      (smoking, time of sunlight exposure, physical activity), medical history
      (cataract, hypertension, glaucoma, drug intake and body-mass index). Clinical
      examination included visual acuity measurement, anterior and posterior segment
      examination, fundus photography grading using The International Classification
      and Grading System. Any image was further classified according to the Clinical
      Age-Related Maculopathy Staging (CARMS) system. RESULTS: 210 patients (79%) of a
      farmer community participated the study. Prevalence of ARM resulted in 38.5%,
      drusen larger than 125 micron were found in 14.81%, AMD was 4.28%. The
      attributable risk estimate, reveal that age (p = 0.014), prior cataract surgery
      (p = 0.00) and hypertension history (p = 0.005), have the greatest impact on the
      prevalence of ARM in the community. A vegetable based diet, seems to prevent such
      effect (p = 0,007). CONCLUSIONS: This study show age as the only dominant
      invariable factor. Prior cataract surgery and hypertension seems to play an
      effective role in increasing the risk of maculopathy. Our results provides
      further evidence that a diet poor in alcohol, rich in vegetables and in
      polyunsaturated fat could reduce risk of AMD.

PMID- 19756318
TI  - [Cognitive research about the use of virtual worlds among the students enrolled
      to the faculty of medicine and surgery "Campus Bio-Medico University" in Rome].
AB  - BACKGROUND AND AIMS: The main difference between a virtual reality and a generic
      representation is to be directly involved into the action you are performing. As
      a matter of fact, within the shift from real to virtual world, our biological
      physique does not mutate but is amplified and connected to the virtual world by
      technological interfaces. Training using a virtual reality simulator is an option
      to supplement (or replace) standard training. One of the two main goals of our
      study is to test, at first, how much students enrolled to the Faculty of Medicine
      at "University Campus Bio-Medico of Rome" are familiar with synthetic worlds, how
      long they have been using them and how they would like their Avatar to look like.
      Moreover, the second aim is to collect students' opinion about the use of
      virtual, interactive environments to enable learning and participation in
      dynamic, problem based, clinical, virtual simulations. Simulations might be used
      to allow learners to make mistakes safely in lieu of real life situations, learn
      from those mistakes and ultimately to improve performances by subsequent
      avoidance of those mistakes. MATERIALS AND METHODS: The selected approach to the
      study is based on a semi-structured questionnaire made of 14 questions
      administered to all the medical students. RESULTS: Most of the students appear
      not to be very confident with virtual worlds mostly because of a lack of
      interest. However, a large majority of them are likely to use a virtual world for
      fun or escaping from reality. Students would select and customize their Avatar by
      giving her/him the same sexual identity, same figure, same social class but
      different employment. CONCLUSIONS: It is important to notice that a wide majority
      of the students is interested in practicing on a virtual world in order to manage
      new experiences and being able to face them; their willing is to get benefits
      from the ability to make mistakes in a safe environment as well as to record a
      positive impact on their understanding.

PMID- 19756319
TI  - [Algometric approach in the diagnostic evaluation of chest pain].
AB  - OBJECTIVE: To contribute to a global clinical evaluation of the patients with
      chest pain, giving a quantitative analysis of the painful experience in the
      sensory, emotional, value and mixed component and searching significant
      differences among the different causes of the symptom. MATERIALS AND METHODS: We
      have administered the "Questionario Italiano del Dolore" by De Benedictis et al.
      to 92 patients with chest pain, who were divided into 4 diagnostic groups (acute
      coronary syndrome, coronary artery disease, oesophagus-gastric disease and other)
      and compared for the quantitative-qualitative features of the associated pain.
      RESULTS: PRIrcE (Global Value Component) resulted higher in the group "other" (A)
      compared to the patients with acute ischemic heart disease (CIA), with a
      statistically significant difference (test U-Mann-Whitney; p = 0.04). This group
      shows statistically significant differences in the emotional component (PRIrcA; p
      = 0.01) even compared to pain associated with oesophagus-gastric disease (G). In
      regard to PRIrcA, the difference between G group and the group of patients with
      chronic ischemic heart disease (CIC), as well as the "double" category, resulted
      markedly significant (p = 0.03 and p = 0.01 respectively). We extrapolated the
      "describers" chosen by at least 50% of patients in every category and obtained
      the semantics configuration of chest pain for every diagnosis. CONCLUSIONS:
      PRIrcE resulted lower in CIA group. PRIrcE e PR-IrcA are more represented in CIC
      group. The same conclusion is valid in the differentiation of pain between CIA
      and G group and between CIA and A group (the most representative of chronic
      pain). We found higher values in emotional component compared to pain of new
      onset as pain becomes chronic.

PMID- 19756320
TI  - Our experience on pain palliation of bone metastasis with Sr-89 or Sm-153 in
      cancer patients resistant to a conventional analgesic therapy. A retrospective
      study.
AB  - OBJECTIVES: These retrospective study is aimed to evaluate the efficacy of
      therapy with Stronthium-chloride 89 (89SrCl) and Samarium 153 conjugated with
      ethylenediaminetetramethylene phosphonic acid (153Sm-EDTMP) in the palliation of
      bone pain due to metastatic malignancy. MATERIALS AND METHODS: The study refers
      to a presentation sample of 27 patients with bone metastases caused by different
      cancers (16 prostate, 5 breast, 6 lung) who were enrolled and followed-up for
      11.5 +/- 6.3 months. 89SrCl (150MBq) was administered in 17 pts, 153Sm-EDTMP (37
      MBq/Kg) in 10 pts. All patients showed multiple metastatic sites of 99Tc-HDP
      uptake documented by a standard bone scintigraphy. Effectiveness of treatment was
      evaluated by questionnaires about pain and quality of life, Karnofsky index,
      specific cancer markers, a post-treatment bone scintigraphy. Presence of flare
      reaction and haematological toxicity were evaluated too. RESULTS: Questionnaire
      scores decreased both in patients treated with 89SrCl and in those given 153Sm
      EDTM, without significant difference. Karnofsky index significantly increased
      only in patients with prostate cancer. After therapy, there were no significant
      changes of tumor marker levels, neither in bone scintigraphic pattern. Flare
      reaction occurred in 44% of the cases within 2 weeks from the therapy. Remarkable
      variations of platelets and leukocytes occurred in 33.3% and 18.5% of patients,
      respectively, independently of the radiopharmaceutical used, but reversed within
      6 weeks after therapy. CONCLUSIONS: Radionuclide therapy with bone-seeker agents
      89Sr and 153Sm in the palliation of painful bone metastases allows a
      partial/total relief of pain with an improvement of quality of life. No tumoricid
      effect was found. Haematological toxicity was limited and reversible. Patients
      with prostate cancer seem to have a higher response rate.

PMID- 19756321
TI  - [MDCT in GIST evaluation.].
AB  - AIM: The aim of our study was to evaluate the accuracy of MDCT in the study of
      gastrointestinal stromal tumour (GIST), and to compare CT results with
      histological findings. MATERIALS AND METHODS: MDCT exams of 18 patients with 19
      lesions, with histological proven GISTs diagnosis, were retrospectively evaluated
      in order to assess the localization, the size, the contours, as well as the CT
      pattern and enhancement of the lesions. All the tumors were recorded with
      Fletcher and Miettinen classification, which evaluate the risk assessment in the
      gastrointestinal stromal tumours. CT findings were correlated with histological
      results after surgery. RESULTS: MDCT properly identified the localization and the
      size in all cases. CT features essentially agreed with histological features.
      CONCLUSIONS: The immunopositivity to c-KIT (CD117) is the key to making a
      diagnosis of GIST. CT is the modality of choice to study these neoplasms,
      evaluating the tumour's site and size with high accuracy. In our experience MDCT
      proved to be a valid diagnostic tool, highly correlated with histological
      features.

PMID- 19756322
TI  - Predisposing factors, clinical and microbiological aspects of bacterial
      keratitis: a clinical study.
AB  - PURPOSE: To identify predisposing factors and to evaluate clinical and
      microbiological characteristics of bacterial keratitis. MATERIALS AND METHODS: A
      retrospective analysis was performed on the charts of patients hospitalized for
      microbial keratitis and treated at the Department of Ophthalmology of the
      Policlinico Umberto I Hospital, Rome, Italy. The study was performed during a 42
      month period. Risk factors, clinical and microbiological data were collected.
      RESULTS: A total of 65 patients with bacterial keratitis were documented. Contact
      lens wear was the most common risk factor (46.1%). Trauma or a history of
      keratopathy was found in 18.5% and 15.4% of cases, respectively. An organism was
      identified in 62% of cases. 74% of all positive cultures involved gram negative
      bacteria. The most frequently cultured organism was Pseudomonas aeruginosa alone
      (72.2%) or in combination with other microorganisms (16.7%). Fifty-eight per cent
      of patients had visual acuity better than the level at admission, and 12% had
      very poor visual outcome. CONCLUSIONS: Contact lens wear is the most important
      risk factor. The role of initial therapy for microbial keratitis remains
      important.

PMID- 19756323
TI  - [Proctological surgery: advantages derived from the use of an innovative
      detergent in the post-operative period].
AB  - BACKGROUND: This study was aimed to verify the efficacy, in terms of healing,
      reepithelization and discomfort, of a detergent cream to be locally used after
      surgery for the most frequent pathologies of anal canal and perineal region.
      MATERIALS AND METHODS: The study was carried out on a "presentation sample" of 40
      patients, 30 with clinico-instrumental diagnosis of III-IV degree haemorrhoids,
      10 with diagnosis of chronic anal fissures, provided by 5 Colonproctological
      Centers, who entered a clinical follow-up after colonproctological surgery for
      their respective pathologies. The tested detergent cream (Anonet liquid) is
      composed by natural substances, such as Aloe vera, Hamamelis, Calendule e
      Hippocastane, as the lenitive and antiinflammatory principles, and Elastine, as a
      stimulatory agent of dermal elastic fibers, plus zincus oxide that has a
      protective, reparative and lenitive action, rice's starch with an anti
      inflammatory action, liver fish oil and potassium glicirizzinate with high
      lenitive and anti-inflammatory action. The product does not contain strong
      tensioactive substances as well as preservants. The patients were asked to apply
      the cream on the perianal and perineal region twice a day for at least 12 days
      after surgery. RESULTS: The study demonstrated that in 84% of tested patients the
      prescribed cream has favoured the prevention of infective complications by
      stimulating a normal reepithelization, and diminished the anal discomfort related
      to burning and pruritus. The cream did not cause irritative and allergic
      manifestations, skin damage as well as pharmacological toxicity. CONCLUSIONS: The
      post-surgical use of the tested detergent cream, composed by the above-cited
      active principles, is recommended for locally preventing the infections,
      promoting the reepithelization, minimizing the perineal discomfort in patients
      operated of haemorrhoids and anal fissures.

PMID- 19756324
TI  - Bilateral acute angle closure glaucoma and myopia induced by topiramate.
AB  - Topiramate is used in the management of epilepsy and migraine. In the present
      paper we present a case of bilateral acute angle closure glaucoma associated with
      myopia following the use of topiramate. The patient was admitted to our ward.
      Complete ophthalmological examination was carried out along with
      ultrabiomicroscopy of the anterior segment and confocal microscopic study of the
      corneal endothelium. Patients on treatment with topiramate should be monitored
      during the first two weeks of therapy and the drug should be discontinued in case
      of visual disturbances or other ocular symptoms.

PMID- 19756325
TI  - [Severe hypertriglyceridemia without organ complications in an alcoholic non
      diabetic patient].
AB  - A case report of a non-diabetic alcoholic patient (ethanol intake >220 g/d) who
      experienced severe hypertriglyceridemia (12.679 mg/dL) without pancreatitis or
      detectable genetic factors responsible for severe dyslipidemia is described.
      Following the normalization of triglyceride and cholesterol levels, through lipid
      free parenteral nutrition therapy, a regimen of alcohol withdrawal and a well
      balanced diet with less than 10% saturated fat maintained a normal lipid profile
      without requiring any lipid-lowering drug. The absence of organ damage in the
      patient is likely to be attributed to the short duration of the elevated
      triglyceride peak. The treatment of this disorder does not necessarily require
      LDL-apheresis but can be simply managed by parenteral therapy provided that no
      other risk factors are present.

PMID- 19756326
TI  - [Triage in the emergency department. Practical and ethical issues].
AB  - Triage is a complex and dynamic decisional process composed of sequential actions
      and necessary evaluations in order to establish the priority of access to medical
      attention in emergency care. In the Triage not only medical-biological knowledge
      is important but also the methods that together are inspired by ethical models.
      Following the historical considerations and after having brought out the methods
      and practice used in various countries and also having underlined the personal
      experience of the Emergency Department of the Emergency Department of the
      University Policlinic of the "Sapienza" University of Rome (Italy), the biggest
      hospital in Europe, the authors emphasized the nursing care in the "triage" and
      support the necessity of an adequate training period not only to acquired the
      technical knowledge required but also the psychological and social interaction as
      well as moral and practical competence. By "practical" we intend it to be
      explicitly a dimension in which moral competence has been acquired in using
      concrete first person action in a virtuous way towards the betterment of the sick
      person using the best modes of justice.

PMID- 19756327
TI  - [Is body surface area (BSA) suitable for indexing renal and dialysis clearances
      and other physiological parameters? A theoretical approach and a critical
      analysis (part 3)].
AB  - Many parameters of biological functions, interesting different branches of
      medicine, have to be indexed by the same value for each other comparison between
      single individuals or between-within groups. Body Surface Area (BSA) and 1.73 m2
      reference value are probably the most used tools for indexation, but a growing
      number of scientific papers emphasize the risk of under or over estimates of data
      by BSA indexation in overweight--obese or on the contrary underweight
      individuals. This study has been planned to evaluate this problem a) by a
      theoretical approach, indexing to 1.73 m2 the creatinine clearance (CtCl) in an
      ideal population and b) analysing and debating the doubts and problems about the
      indexation by BSA in many fields, the possibilities of indexation by other
      methods, or to use BSA with different approach, to reduce the risk of bias,
      evaluating the possibility of this target in a real population of 45 men and 84
      women undergoing Peritoneal Dialysis (PD)--III--There is a lack of significative
      correlation between BSA and GFR, this one on the contrary significantly
      correlated with lean body mass and body water, possible alternatives to BSA.
      Researches performed to validate the indirect estimates of above variables by
      creatinine excretion and bioimpedance don't seem up till now to give sufficient
      evidences for a general acceptance. In conclusion, it would be advisable or to
      drop the indexing by BSA or, if necessary, to use it by different methods, as
      theoretically shown in this paper.

PMID- 19756328
TI  - Antiviral drug treatment for emerging swine flu.
AB  - Of several infections, influenza virus infection is considered a serious problem.
      Emerging of atypical influenza virus infection is a big challenge in antiviral
      drug treatment. The efficacy of antiviral drug in atypical influenza is still
      doubtful. In this specific article, the author will discuss and detail on
      antiviral drug treatment for the new emerging swine flu. The problems for
      antiviral drug treatment in case of swine flu are discussed. The current practice
      on usage of all available antiviral drugs in swine flu is detailed. Also, the
      obstacles in usage of antiviral drug treatment in swine flu are summarized in
      this article.

PMID- 19756329
TI  - An unusual presentation of alveolar hemorrhage.
AB  - We report the case of a female patient with an atypical case of alveolar
      haemorrhage secondary to disseminated strongyloidiasis. Although uncommon,
      clinicians should consider the diagnosis of pneumonia by disseminated
      strongyloidiasis in patients with endemic exposure to Strongyloides stercoralis
      who present with symptoms of cough, wheezing, and dyspnoea. Primary care
      physicians should strongly consider screening for strongyloidiasis in patients
      from endemic areas prior to considering the use of steroids or any other
      immunosuppressants. The best screening test would be serological testing.

PMID- 19756330
TI  - Recent trends in lung cancer and its association with COPD: an analysis using the
      UK GP Research Database.
AB  - BACKGROUND: The association between lung cancer and COPD has not been
      investigated in the primary care setting. METHOD: We determined the recent trends
      of lung cancer in COPD patients in the UK during the period 1991-2004, by
      investigating the population aged 45 and over in the General Practice Research
      Database. RESULTS: The annual-incidence rates of lung cancer per 10,000 person
      years were at least four-fold higher in patients with prior COPD (increasing from
      45 to 64 in men; 29 to 48 in women) compared with the general population (from 10
      to 15 in men; 5 to 10 in women). These lung cancer trends had significant annual
      increases that were similar in men (5%) and in women (5.5%) with prior COPD; in
      contrast, the annual increases of lung cancer incidence rates in the general
      population differed by gender, being 4% in men but double in women (8%). The
      three-year survival for lung cancer patients among those with prior COPD was
      almost half that of the general population (15% versus 26%; p<0.01) and the
      highest mortality was observed in men aged 45-64 (83.79 per 100 person-years; 95%
      CI: 69.66-97.92). CONCLUSION: These results support the association of COPD and
      lung cancer observed in other settings.

PMID- 19756331
TI  - The effectiveness of a social marketing model on case-finding for COPD in a
      deprived inner city population.
AB  - AIM: To evaluate the effectiveness of a social marketing model on case-finding
      for COPD in a population with high smoking rates and COPD prevalence. METHODS: A
      two-week marketing campaign was conducted using high visibility posters, leaflets
      distributed with the local newspaper, and the creation of a free automated COPD
      information line. The primary outcome measure was the number of newly-diagnosed
      cases of COPD as a result of the campaign. Secondary outcomes measures were: the
      number of phone calls to the information line up to four weeks after the end of
      the campaign; the number of individuals who presented to their general
      practitioner (GP) for spirometry as a result of the campaign; and responses to a
      questionnaire sent to members of the public to analyse and assess the visibility
      and impact of the campaign. RESULTS: Ten people came forward to have spirometry
      performed and all had non-obstructive results. Nine calls were made to the
      dedicated COPD phone line. 135 out of 400 members of the public (34%) responded
      to the questionnaire; of these, only 34 (25%) recalled seeing a campaign poster.
      CONCLUSIONS: Posters and leaflets from this campaign were visible but only led to
      10 individuals coming forward for spirometry, none of whom had COPD. This form of
      healthcare marketing was costly and not effective for COPD case-finding in our
      area.

PMID- 19756332
TI  - Cortical laminar necrosis after carotid stenting.

PMID- 19756333
TI  - [Splitting of supplemental revenues in intensive care medicine].
AB  - In patient care several clinical departments are often involved in the treatment
      of a single case. Due to this shared work and internal patient transfer between
      departments the respective departments have to share the single reimbursement sum
      which is granted for each hospital case in the German DRG system. The intensive
      care unit in particular, at least if maintained as an independent department, has
      a high rate of internal transfers and most of the patients will be transferred
      back to the original department prior to discharge from hospital. Different
      models have been suggested regarding the splitting of DRG reimbursement between
      clinical departments, however, no research has been done on the splitting of
      supplemental revenues. The allocation of supplemental revenues is especially
      complex for revenues generated over many days of hospital care or for clustered
      revenues. In most cases the supplemental revenues are simply allocated to the
      department from which the patient is ultimately discharged. This would lead to a
      significant economic risk for the intensive care unit, as a considerable
      proportion of medical services which are eligible for triggering supplemental
      revenues are applied there. In this study all cases treated in two intensive care
      units in a university hospital in 2007 were analyzed in which supplemental
      revenue-related medical services were performed over a longer period of time or
      graduated according to different amounts. In a total of 385 cases, 691
      supplemental revenues were analyzed. Three different methods of supplemental
      revenues allocation were analyzed regarding the financial impact on the intensive
      care unit: allocation to the department from which the patient is discharged,
      allocation according to the length of stay in a particular department (in this
      case the intensive care unit) and allocation based on actually documented medical
      services eligible for supplemental revenues. The supplemental revenues take up a
      considerable share of the total reimbursement for intensive care. Based on the
      first 2 allocation methods the intensive care unit would receive 20% less
      supplemental revenues compared to the third allocation method, which supposedly
      reflects best the actual costs.

PMID- 19756334
TI  - [Successful treatment of extreme metabolic acidosis and profound hypothermia].
AB  - A case of extreme metabolic acidosis (pH 6.6) and severe hypothermia (27.3
      degrees C) is reported. The patient's anamnesis and medical examination led to
      the assumption of ketoacidosis. Pronounced ketoacidosis is not unusual in
      juvenile diabetics type 1 and the incidence in Europe is reported to be between
      15 and 70% for all type 1 diabetics. The case describes the targeted therapy of
      controlled re-warming to avoid neurological damage.

PMID- 19756335
TI  - [Cave canulam et dilatationem. Cardiopulmonary resuscitation and surgical repair
      of a vessel perforation following central venous catheterization].
AB  - A 58-year-old female patient was scheduled for minimally invasive cardiac
      surgery. For drainage of venous blood to the heart-lung machine insertion of a
      central venous large diameter catheter was a prerequisite. During insertion into
      the right internal jugular vein by the anesthesiologist a life-threatening
      perforation of the subclavian artery occurred. The patient suffered hemorrhagic
      shock and advanced cardiac life support was carried out for approximately 18 min.
      Immediate surgical repair was successful and the originally planned operation was
      then performed. Concurrently, mild therapeutic hypothermia was established for 24
      h to protect the cerebrum. Within 4 days the patient recovered without any
      neurological deficits.

PMID- 19756336
TI  - Childhood vaccination schedules in Europe vary widely. Is this a problem?
AB  - Childhood vaccination programmes in Europe are basically very safe and effective.
      On the other hand there are very large differences between countries in the way
      they are organised. In this paper we analyse the immunisation schedules used in
      29 European countries to highlight similarities and differences. One of the most
      evident differences is the total number of doses administered under 18 years of
      age, which ranges between 4 and 7 if we consider DT-containing vaccines. Any
      change in vaccination schedules is associated with costs. Thus, this process is
      worthy only if it can lead in the long run to an overall improvement in the
      national vaccination programmes. National sovereignty in the area of vaccination
      programmes prevails; therefore any step forward will be feasible only if
      consensus in Europe is reached.

PMID- 19756337
TI  - [Current vaccination coverage and immunization gaps of children and adolescents
      in Germany].
AB  - Available data show increasing vaccination coverage of children and adolescents
      in recent years in Germany. Vaccination coverage of children against diphtheria,
      tetanus, polio and haemophilus influenzae Type b is high. Vaccination gaps exist
      for pertussis, hepatitis B and for the second measles, mumps and rubella doses.
      Coverage is still insufficient to achieve effective herd immunity and measles
      elimination. Data from the representative German Health Interview and Examination
      Survey for Children and Adolescents reveal that vaccination of infants is
      markedly delayed compared to recommendations of the German Standing Committee on
      Vaccination (STIKO). Particularly older children and adolescents are often not
      fully vaccinated or are even unvaccinated. A high proportion is missing the
      recommended booster doses against diphtheria, tetanus, pertussis and polio.
      Vaccination compliance especially regarding completeness and timeliness is lower
      in western than eastern Germany, as well as in children of vaccine sceptics and
      foreign-born children. More comprehensive surveillance of vaccination coverage
      and adverse events following immunization as well as the implementation of a
      national immunization plan focussing on closure of immunization gaps could lead
      to improved vaccination coverage.

PMID- 19756338
TI  - [Repeated prevalence investigations of nursing home-associated  infections as a
      tool to assess the hygienic quality of care].
AB  - The rate of healthcare-associated infections can be regarded as an important
      outcome parameter of the hygienic quality of care in nursing homes. Our study
      aimed to evaluate the applicability of repeated prevalence investigations as a
      tool for surveillance of healthcare-associated infections in nursing homes. From
      December 2006 to September 2007 a total of five prevalence investigations were
      conducted in four nursing homes each (n=2,369 residents). Initially, defined
      structural and procedural parameters of the hygienic quality of the four nursing
      homes were evaluated based on a detailed inspection and a checklist including 40
      parameters. The results showed a uniformly high level of the hygienic quality
      with only minor variation (mean 84%, range 75%-93% of parameters fulfilled). In
      total, the prevalence of healthcare-associated infections was 6.8%, with a marked
      increase with higher categories of dependency (3.5%, 4.0%, 8.5%, and 12.3%,
      respectively, in the categories 0, I, II, and III of the German grading of
      skilled nursing care). Respiratory tract (4.1%), skin/soft tissue (1.5%), and
      urinary tract infections were the most prevalent healthcare-associated
      infections. Respiratory tract infections showed a marked seasonal pattern. During
      the second prevalence investigation (February 2007), an outbreak of upper
      respiratory tract infections occurred in one of the nursing homes (attack rate,
      17%). The crude prevalence rates showed considerable differences between the four
      nursing homes; however, after adjusting for the different categories of
      dependency, the standardized infection rates (SIR) were largely comparable
      (excluding the outbreak). After inclusion of the outbreak, the SIR of the
      specific nursing home was significantly higher compared to all other nursing
      homes. In conclusion, our study shows that repeated prevalence investigations can
      be an easy to use tool for surveillance of healthcare-associated infections as a
      surrogate parameter of the hygienic quality in nursing homes. This implies a
      knowledge of the seasonality of specific infections and a risk adjustment
      according to the categories of dependency. The primary intention of surveillance
      should be the identification of hygienic problems. However, the resources should
      preferentially be focused on hygienic structures and processes.

PMID- 19756339
TI  - Continuity from suicidal ideations to suicide attempts? An investigation in 18-55
      years old adult Iranian Kurds.
AB  - OBJECTIVES: Suicidal ideation as a critical point for the identification of
      individuals at risk of committing suicide/attempting suicide. METHODS: Cross
      sectional study; random sample; n = 1,000; attitudes towards Suicide
      questionnaire. RESULTS: Iranian Kurds reported very few suicide attempts, whereas
      the prevalence of reported suicidal thoughts was found to be very high. The
      reported frequency of suicidal thoughts and the number of suicide attempts during
      the last year was significantly higher than that from earlier in life.
      CONCLUSIONS: A continuum of suicidal behaviour is supported; but, this did not
      include self-reported suicide attempts. The reported frequency of suicidal
      thoughts and suicide attempts was highly dependent on applied response categories
      and the considered timeframe, which has to be considered thoroughly when
      interpreting related results.

PMID- 19756340
TI  - Perineal leiomyoma mimicking complex Bartholin mass.
AB  - Leiomyomas of the external genitalia are uncommon soft tissue tumors. We report
      the case of a 47-year-old woman with perineal leiomyomas mimicking Bartholin's
      gland mass according to the preoperative magnetic resonance imaging (MRI)
      findings. Leiomyomas in the vulvar region should be differentiated from
      complicated Bartholin's gland cysts and preoperative MRI findings may be
      misleading. The complete surgical excision should be the choice of treatment.

PMID- 19756341
TI  - A validated self-administered female pelvic floor questionnaire.
AB  - INTRODUCTION AND HYPOTHESIS: The aim of this study was to validate a self
      administered version of the already validated interviewer-administered Australian
      pelvic floor questionnaire. METHODS: The questionnaire was completed by 163 women
      attending an urogynecological clinic. Face and convergent validity was assessed.
      Reliability testing and comparison with the interviewer-administered version was
      performed in a subset of 105 patients. Responsiveness was evaluated in a subset
      of 73 women. RESULTS: Missing data did not exceed 4% for any question. Cronbach's
      alpha coefficients were acceptable in all domains. Kappa coefficients for the
      test-retest analyses varied from 0.64-1.0. Prolapse symptoms correlated
      significantly with the pelvic organ prolapse quantification. Urodynamics
      confirmed the reported symptom stress incontinence in 70%. The self and
      interviewer-administered questionnaires demonstrated equivalence. Effect sizes
      ranged from 0.6 to 1.4. CONCLUSIONS: This self-administered pelvic floor
      questionnaire assessed pelvic floor function in a reproducible and valid fashion
      and due to its responsiveness, can be used for routine clinical assessment and
      outcome research.

PMID- 19756342
TI  - TVT or TOT? When to avoid retropubic trocar passage.
AB  - Most surgeons have a preferred method for placing a minimally invasive
      suburethral sling for treatment of stress urinary incontinence. However, unique
      clinical circumstances may necessitate altering this approach. We describe two
      cases for which a retropubic approach to sling placement may be contraindicated.

PMID- 19756343
TI  - Genome-based expression profiles study for the pathogenesis of pelvic organ
      prolapse: an array of 33 genes model.
AB  - INTRODUCTION AND HYPOTHESIS: To explore the potential molecular mechanisms
      contributing to the pathogenesis of pelvic organ prolapse (POP) with the aid of
      high-density oligonucleotide microarrays. METHODS: We compared microarray gene
      expression profiles in pelvic connective tissue from women with POP and
      nonprolapse controls. The round ligament and uterosacral ligament tissues were
      removed from each subject at the time of laparoscopic hysterectomy. RNA was then
      extracted, and all labeled samples were hybridized to ABI Human Genome Survey
      Microarray version 2.0 (Applied Biosystems, CA, USA). RESULTS: The Mahalanobis
      distance in hierarchical cluster analysis revealed a model of 33 genes, which
      contained high expressions of round and uterosacral ligaments from women with
      POP. According to gene ontology, the expressions of mitochondrial genes encoding
      ribosomal protein were upregulated. Genes involved in potential interactions with
      mitochondrial electron transport, nucleosome assembly, cell cycle, and apoptosis
      were also upregulated. As a result, defective mitochondrial translation caused by
      ribosomal protein contributes to the potential molecular etiology of POP. Such
      changes, jointly termed "remodeling of pelvic connective tissue", can constitute
      an important long-term consequence of POP. CONCLUSIONS: Our results support the
      use of genome-based expression profiling as a commonplace platform for diagnostic
      tests of POP.

PMID- 19756344
TI  - The role of calpain-calpastatin system in the development of stress urinary
      incontinence.
AB  - INTRODUCTION AND HYPOTHESIS: The objective of this study is to investigate the
      expression of calpain-1, calpain-2, and calpastatin in the human periurethral
      vaginal tissues and to show the potential link between calpain system and stress
      urinary incontinence (SUI). METHODS: The periurethral vaginal tissues of 39 women
      with SUI and 31 women without SUI were collected to detect the expressions of
      calpains and calpastatin by using semi-quantitative competitive reverse
      transcription-polymerase chain reaction and Western blotting. RESULTS: There were
      no significant differences on the expressions of calpain-1 at the levels of
      messenger RNA (mRNA) and protein in both groups (P > 0.05), but the patients with
      SUI had significantly higher levels of calpain-2 mRNA and protein than the
      control (P < 0.05); and the mRNA expressions of calpastatin in women with SUI
      were significantly higher than the control (P < 0.05), while the protein
      expressions were significantly lower when compared to the control (P < 0.01).
      CONCLUSIONS: Overexpression of calpain-2 and low expression of calpastatin may
      involve in the pathological development of SUI.

PMID- 19756345
TI  - Pelvic floor muscle function in a general female population in relation with age
      and parity and the relation between voluntary and involuntary contractions of the
      pelvic floor musculature.
AB  - INTRODUCTION AND HYPOTHESIS: The objective of this study is to describe pelvic
      floor muscle function (PFMF) in relation to age and parity in a general female
      population and to test whether strength/endurance measurements represent all
      functions of the pelvic floor musculature. METHODS: A cross-sectional study was
      performed on 95% of the women aged 45-85 years from a small Dutch town. Validated
      questionnaires were used to obtain general information, and vaginal examination
      to test PFMF was performed on 649 women. Chi-square tests were used to analyse
      the relation between PFMF versus age and parity. Analysis of variance was used to
      compare muscle strength and endurance to the other PFMF items. RESULTS: Response
      rate to the questionnaire was 62.7% (1,869/2,979). PFM strength and endurance are
      not positively associated with the effective involuntary muscle contractions
      during coughing. CONCLUSIONS: Voluntary muscle contractions decreased with age,
      but there was no relation with parity. Muscle strength and endurance measurements
      alone are not sensitive enough to determine PFMF.

PMID- 19756346
TI  - Association of IL-15 polymorphisms with bone mineral density in postmenopausal
      Korean women.
AB  - Interleukin-15 (IL-15) has been suggested to participate in bone metabolism by
      stimulating osteoclast differentiation and mediating inflammatory bone loss. This
      study investigated the effect of IL-15 gene polymorphisms on the bone mineral
      density (BMD) and bone fracture rates of postmenopausal women. Sequencing of the
      IL-15 gene in 24 Koreans revealed 16 single-nucleotide polymorphisms (SNPs), of
      which five were selected for further study. Postmenopausal Korean women (n = 844)
      were genotyped for these SNPs, and their BMDs and risk of fractures were
      assessed. It was found that the +20A > G, +13467C > A, +13653A > T, and +13815A >
      T IL-15 gene polymorphisms were significantly associated with the BMD of the
      lumbar spine and femoral neck and that their effects were gene-dose dependent.
      BMD was reduced when the minor allele of +13467A and +13653T or the common allele
      of +20A and +13815A was present. Haplotype (ht) analyses revealed that ht1 (GCAT)
      and ht2 (AATA) were associated with BMD of the lumbar spine and femoral neck.
      However, there was no association between the risk of fracture and IL-15 SNPs or
      hts. These results suggest that the +20A > G, +13467C > A, +13653A > T, and
      +13815A > T SNPs in the IL-15 gene affect BMD and, thus, could be genetic markers
      of osteoporosis.

PMID- 19756347
TI  - Combination of nanoindentation and quantitative backscattered electron imaging
      revealed altered bone material properties associated with femoral neck fragility.
AB  - Osteoporotic fragility fractures were hypothesized to be related to changes in
      bone material properties and not solely to reduction in bone mass. We studied
      cortical bone from the superior and inferior sectors of whole femoral neck
      sections from five female osteoporotic hip fracture cases (74-92 years) and five
      nonfractured controls (75-88 years). The typical calcium content (Ca(Peak)) and
      the mineral particle thickness parameter (T) were mapped in large areas of the
      superior and inferior regions using quantitative backscattered electron imaging
      (qBEI) and scanning small-angle X-ray scattering, respectively. Additionally,
      indentation modulus (E) and hardness (H) (determined by nanoindentation) were
      compared at the local level to the mineral content (Ca(Ind)) at the indent
      positions (obtained from qBEI). Ca(Peak) (-2.2%, P = 0.002), Ca(Ind) (-1.8%, P =
      0.048), E (-5.6%, P = 0.040), and H (-6.0%, P = 0.016) were significantly lower
      for the superior compared to the inferior region. Interestingly, Ca(Peak) as well
      as Ca(Ind) were also lower (-2.6%, P = 0.006, and -3.7%, P = 0.002, respectively)
      in fracture cases compared to controls, while E and H did not show any
      significant reduction. T values were in the normal range, independent of region
      (P = 0.181) or fracture status (P = 0.551). In conclusion, it appears that the
      observed femoral neck fragility is associated with a reduced mineral content,
      which was not accompanied by a reduction in stiffness and hardness of the bone
      material. This pilot study suggests that a stiffening process in the organic
      matrix component contributes to bone fragility independently of mineral content.

PMID- 19756348
TI  - The effect of recombinant PTH(1-34) and PTH(1-84) on serum ionized calcium, 1,25
      dihydroxyvitamin D, and urinary calcium excretion: a pilot study.
AB  - We investigated the frequency of hypercalcemia and/or hypercalciuria following
      parathyroid hormone (PTH) 1-34 and 1-84 administration in a crossover trial. Ten
      postmenopausal osteoporotic women previously treated with bisphosphonates were
      subdivided into two groups of five patients each. A 24-h urine collection to
      determine baseline calcium (Ca) and creatinine (Cr) the day before administration
      of PTH was followed by determination of serum ionized Ca (Ca(2+)), Cr, 25(OH)D,
      and 1,25(OH)(2)D at baseline. Thereafter, 100 mcg of PTH(1-84) or 20 mcg of PTH(1
      34) was administered. A 24-h urinary collection and blood samples 2, 4, and 24-h
      after each PTH administration were again taken. One week after the first PTH
      administration patients were rechallenged with the second PTH. The PTH peptides
      did not differ with respect to changes in Ca(2+) at 2, 4, and 24 h postinjection;
      at the last time point the values were virtually identical to the initial values.
      There was no difference in urinary Ca on the day following PTH injection compared
      to baseline, in terms both of Ca/Cr and of Ca excretion. The two PTH peptides did
      not differ with respect to changes in 1,25(OH)(2)D at 2, 4, and 24 h considering
      both the absolute values and the percent changes with respect to baseline (24-h 1
      84 = 125.6 + or - 58.6 pg/ml, 153% increase; 1-34 = 124.1 + or - 64.7, 130%). Our
      results indicate no difference in postinjection serum Ca(2+), 1,25(OH)(2)D, or
      urinary Ca excretion after a single dose of either PTH(1-84) or PTH(1-34) in
      patients previously treated with bisphosphonates.

PMID- 19756349
TI  - Clinical study of peroneal artery perforators with computed tomographic
      angiography: implications for fibular flap harvest.
AB  - PURPOSE: Previous studies of cutaneous perforators of the peroneal artery have
      shown great variability, and attest to the significant anatomical variability in
      this region. Furthermore, the vascular anatomy of the region has been considered
      unreliable in the prediction of ideal perforator topography. Preoperative imaging
      has been suggested as a means for improving preoperative awareness, with Doppler
      ultrasound and eco-colour (duplex) ultrasound as useful tools. Multi-detector row
      computed tomographic angiography (CTA or angio CT), has emerged as a significant
      improvement, providing non-invasive operator-independent details of the vascular
      anatomy. We utilised this tool to perform an in vivo, anatomical study of the
      peroneal artery perforators, and demonstrating the usefulness of CTA in planning
      the osteocutaneous free fibula flap. METHODS: Forty-one consecutive patients (82
      limbs) underwent CTA of the lower limb vasculature, with the anatomical details
      of the peroneal artery cutaneous perforators assessed. RESULTS: CTA was able to
      demonstrate the size, course and penetration pattern of all perforators over 0.3
      mm in diameter, with measurements for perforators over 0.8 mm diameter recorded
      for analysis. Of 171 such perforators, accurate identification of the size (mean
      diameter 1.91 mm), course (59.6% septocutaneous, 29.2% musculocutaneous and 11.1%
      septomusculocutaneous) and location was achieved. CONCLUSION: The vascular
      anatomy of peroneal artery perforators is highly variable, and thus there is a
      role for preoperative imaging. CTA can demonstrate cases where there is aberrant
      or non-preferred anatomy, or select the limb of choice for harvest.

PMID- 19756350
TI  - In vitro 3D-kinematics of the upper cervical spine: helical axis and simulation
      for axial rotation and flexion extension.
AB  - PURPOSE: Registration of 3D-anatomical model and kinematics data is reported to
      be an accurate method to provide 3D-joint simulation. We applied this approach to
      discrete kinematics analysis of upper cervical spine (UCS) during axial rotation
      (AR) and flexion extension (FE) to create anatomical models with movement
      simulation including helical axis. METHODS: Kinematics and CT imaging data were
      sampled in ten anatomical specimens. Using technical and anatomical marker
      digitizing, spatial position of segments was computed for five discrete positions
      of AR and FE using a 3D-digitizer. Computerized tomography was used to create
      anatomical models and to assure kinematics and imaging data registration for
      simulation. Kinematics was processed using orientation vector and helical axis
      (HA) computation. RESULTS: Maximal standard error on marker digitizing was 0.47
      mm. Range of motion and coupled movement during AR was in agreement with previous
      in vitro studies. HA location and orientation have shown low variation at the
      occipitoaxial and atlantoaxial levels for FE and AR, respectively. CONCLUSIONS:
      We developed a protocol to create UCS anatomical model simulations including
      three-dimensional discrete kinematics, using previously validated methods. In
      this study, simultaneous segmental movement simulation and display of HA
      variations was shown to be feasible. Although partially confirming previous
      results, helical axis computation showed variations of motion patterns dependent
      on movement, level and specimen. Further in vivo investigations are needed to
      confirm relevance of this method in the clinical field.

PMID- 19756351
TI  - Incidental finding of fenestration of the supraclinoid internal carotid artery
      with appearances on magnetic resonance angiography.
AB  - A case of incidentally diagnosed fenestration of the supraclinoid internal
      carotid artery (ICA) with an associated aneurysm is presented. We present
      appearances on magnetic resonance angiography, which have not been previously
      described. Careful interrogation of the data in volume-rendered and multiplanar
      reformats was required to make the diagnosis. The relationship between
      fenestrations and aneurysms in the anterior circulation is discussed both in
      general terms and with specific regard to the supraclinoid ICA. We also review
      the embryology of the distal ICA, which may help explain the adult anatomy of
      this rare lesion as a failure of caudal separation of the rostral and caudal
      divisions of the primitive distal ICA.

PMID- 19756352
TI  - Viral factors influencing the response to the combination therapy  of
      peginterferon plus ribavirin in chronic hepatitis C.
AB  - Hepatitis C virus (HCV) is a single-stranded RNA virus known for its high genetic
      variability owing to the lack of a proofreading mechanism of its RNA dependent
      RNA polymerase. Until now, numerous studies have been undertaken to clarify the
      correlation between pretreatment HCV genetic variability and the therapeutic
      response. Even with the recent combination therapy of peginterferon plus
      ribavirin for chronic hepatitis C, viral response is variable, and only half of
      treated patients could clear the virus [sustained viral response (SVR)]. In this
      review, the contribution of viral genetic variability affecting the treatment
      outcome is discussed according to each HCV genomic region.

PMID- 19756353
TI  - Trigeminal neuralgia: a plea for microvascular decompression as the first
      surgical option. Anatomy should prevail.
AB  - Arguments are given to plead why micro-vascular decompression should be the first
      surgical option to treat primary trigeminal neuralgias resistant to
      anticonvulsants.

PMID- 19756354
TI  - Chronic sub-dural hematomas: twist drill craniostomy with a closed system of
      drainage, for 48 hours only, is a valuable surgical treatment.
AB  - Twist drill craniostomy with closed drainage system for 48-hour duration is an
      effective treatment of chronic subdural hematomas.

PMID- 19756355
TI  - PEEK cage cervical ventral fusion in spondylodiscitis.
AB  - PURPOSE: Cervical spondylodiscitis is a quite rare finding regarding the number
      and the common location of spinal abscesses in the lumbar region. While in
      thoracic and lumbar discitis, single-step surgery with neural decompression, disc
      space evacuation, and subsequent fusion is well known, there is no such report in
      cervical discitis. Here the authors present their experience with ventral
      polyetherketone (PEEK) cage fusion in cervical spondylodiscitis in a single-step
      procedure. METHODS: Between January 2006 and November 2008, five patients (three
      men, two woman; ages 71, 77, 58, 66 and 66 years) suffering from cervical
      spondylodiscitis and epidural abscess underwent disc evacuation, myelon
      decompression and subsequent ventral fusion using an empty PEEK cage disc
      replacement in one single setting. All five patients presented with significant
      neurological symptoms like cervicobrachialgia, tetraparesis and disturbance of
      the urinary incontinence. In all five patients, disc evacuation, myelon
      decompression and cervical fusion using a PEEK cage disc replacement in a single
      stage surgery were performed. All wounds were closed primarily. Postoperatively,
      all patients received a specific antibiotic therapy for at least 6 weeks.
      RESULTS: This treatment strategy was successful in all patients with respect to
      clinical signs, laboratory parameters and radiological findings. All patients
      improved neurologically. Follow-up revealed a stable osteosynthesis without signs
      of instability. One cage was explanted despite neurological improvement and
      normal infectious parameters at another surgical department. No complications
      were observed. CONCLUSIONS: In all, abscess drainage and ventral fusion with PEEK
      cage disc replacement in one single setting was proven to be a successful
      treatment option in cervical discitis and spinal epidural abscess.

PMID- 19756356
TI  - Treatment of communicating hydrocephalus by a lumbo-omental shunt: case report.
AB  - Based on preliminary experiences from the early 1970s, a patient with chronic and
      severe communicating hydrocephalus has been successfully treated with
      transposition of an omental pedicle to the lumbar subarachnoidal space. This
      patient, who suffered from congenital toxoplasmosis, at the age of 29 years had
      undergone no fewer than 82 shunt revisions. In the 5-year follow-up after
      treatment, she has had no further surgery or other treatment. She is in excellent
      condition and has demonstrated definite signs of improved CSF circulation. This
      case report confirms that a pedicle of the omentum may serve as an effective CSF
      absorber in patients presenting with persistent failures with conventional
      treatments of communicating hydrocephalus, avoiding the use of any implanted
      foreign material.

PMID- 19756357
TI  - Polyomaviruses KI and WU in children with respiratory tract infection.
AB  - The polyomaviruses KI (KIPyV) and WU (WUPyV) have recently been discovered in
      specimens from patients with respiratory tract infections. To analyze the
      frequency and clinical impact in a cohort of pediatric patients in a German
      University Children's Hospital. Nasopharyngeal aspirates or bronchoalveolar
      lavage specimens of 229 children with acute respiratory tract infection were
      screened for KIPyV and WUPyV using polymerase chain reaction-based methods. KIPyV
      was detected in 2 (0.9%) and WUPyV in 1 (0.4%) patients, without co-infections
      with other respiratory viruses but with co-detection of CMV, EBV and HHV 6 in one
      immunocompromised patient. Only a very small proportion (1.3%) of positive
      samples for KIPyV and WUPyV was documented in this study; the clinical relevance
      of these viruses remains unclear and requires further evaluation.

PMID- 19756358
TI  - Sequence and phylogenetic analysis of the RNA1 and RNA2 segments of Korean Rice
      stripe virus isolates and comparison with those of China and Japan.
AB  - Rice stripe virus (RSV) is one of the most destructive pathogens of rice plants
      in East Asia. The RSV genome consists of four single-stranded RNA segments. We
      have determined and compared the complete nucleotide sequences of the RNA1 and
      RNA2 segments and the deduced amino acid sequence of each ORF of the 13 Korean
      RSV isolates and established their relationships with reported RSV sequences from
      China and Japan. Our results showed that the average percent nucleotide
      divergence based on the full-length genome is higher in RNA2 (2.2%) than in RNA1
      (2.0%). The average percent amino acid variation of the RNA-dependent RNA
      polymerase (RdRp), glycoprotein and NS2 genes encoded by viral complementary (vc)
      RNA1, viral RNA2 and vcRNA2, showed 2.8, 2.5 and 6.46%, respectively. On the
      other hand, the average percent nucleotide variation in the intergenic region
      (IGR) of RNA2 among the 13 Korean-RSV isolates was 3.5%. Phylogenetic analysis of
      the 13 Korean, 1 Japanese and 5 Chinese isolates based on their complete
      nucleotide sequences revealed two distinct types of RNA1 and three distinct types
      of RNA2. Most Chinese isolates grouped with one of the RNA1 types, but they were
      distributed among the three types when grouped by RNA2. Japanese isolate T was
      grouped with Korean isolates into one of the RNA1 and RNA2 genotypes. Taken
      together, our results suggest that the RSV population in Korea consists of
      mixtures of RNA1-RNA4 genome segments originating from distinctive ancestors,
      most likely due to either reassortment or recombination events among isolates.

PMID- 19756359
TI  - A novel sugarcane-infecting mastrevirus from South Africa.
AB  - The sugarcane-infecting streak viruses (SISVs) are a diverse collection of
      mastreviruses (family Geminiviridae) within the African streak virus group. Four
      SISVs have currently been described, including the well-characterized maize
      streak virus. Here, we present a full annotated sequence record of an isolate of
      a new SISV species, Saccharum streak virus (SacSV), isolated in South Africa. The
      isolate shares less than 66% identity with any other mastrevirus, but is most
      closely related to Urochloa streak virus (USV), a mastrevirus from Nigeria that
      has until now been an outlier in the African streak virus phylogenetic tree. As
      with USV, the SacSV isolate we have characterized bears no obvious evidence of
      inter-species recombination.

PMID- 19756360
TI  - Expression and characterization of HPV-16 L1 capsid protein in Pichia pastoris.
AB  - Human papillomaviruses (HPVs) are responsible for the most common human sexually
      transmitted viral infections. Infection with high-risk HPVs, particularly HPV16,
      is associated with the development of cervical cancer. The papillomavirus L1
      major capsid protein, the basis of the currently marketed vaccines, self
      assembles into virus-like particles (VLPs). Here, we describe the expression,
      purification and characterization of recombinant HPV16 L1 produced by a
      methylotrophic yeast. A codon-optimized HPV16 L1 gene was cloned into a non
      integrative expression vector under the regulation of a methanol-inducible
      promoter and used to transform competent Pichia pastoris cells. Purification of
      L1 protein from yeast extracts was performed using heparin-sepharose
      chromatography, followed by a disassembly/reassembly step. VLPs could be
      assembled from the purified L1 protein, as demonstrated by electron microscopy.
      The display of conformational epitopes on the VLPs surface was confirmed by
      hemagglutination and hemagglutination inhibition assays and by immuno-electron
      microscopy. This study has implications for the development of an alternative
      platform for the production of a papillomavirus vaccine that could be provided by
      public health programs, especially in resource-poor areas, where there is a great
      demand for low-cost vaccines.

PMID- 19756361
TI  - Dimethyltryptamine and other hallucinogenic tryptamines exhibit substrate
      behavior at the serotonin uptake transporter and the vesicle monoamine
      transporter.
AB  - N,N-dimethyltryptamine (DMT) is a potent plant hallucinogen that has also been
      found in human tissues. When ingested, DMT and related N,N-dialkyltryptamines
      produce an intense hallucinogenic state. Behavioral effects are mediated through
      various neurochemical mechanisms including activity at sigma-1 and serotonin
      receptors, modification of monoamine uptake and release, and competition for
      metabolic enzymes. To further clarify the pharmacology of hallucinogenic
      tryptamines, we synthesized DMT, N-methyl-N-isopropyltryptamine (MIPT), N,N
      dipropyltryptamine (DPT), and N,N-diisopropyltryptamine. We then tested the
      abilities of these N,N-dialkyltryptamines to inhibit [(3)H]5-HT uptake via the
      plasma membrane serotonin transporter (SERT) in human platelets and via the
      vesicle monoamine transporter (VMAT2) in Sf9 cells expressing the rat VMAT2. The
      tryptamines were also tested as inhibitors of [(3)H]paroxetine binding to the
      SERT and [(3)H]dihydrotetrabenazine binding to VMAT2. Our results show that DMT,
      MIPT, DPT, and DIPT inhibit [(3)H]5-HT transport at the SERT with K ( I ) values
      of 4.00 +/- 0.70, 8.88 +/- 4.7, 0.594 +/- 0.12, and 2.32 +/- 0.46 microM,
      respectively. At VMAT2, the tryptamines inhibited [(3)H]5-HT transport with K ( I
      ) values of 93 +/- 6.8, 20 +/- 4.3, 19 +/- 2.3, and 19 +/- 3.1 muM, respectively.
      On the other hand, the tryptamines were very poor inhibitors of [(3)H]paroxetine
      binding to SERT and of [(3)H]dihydrotetrabenazine binding to VMAT2, resulting in
      high binding-to-uptake ratios. High binding-to-uptake ratios support the
      hypothesis that the tryptamines are transporter substrates, not uptake blockers,
      at both SERT and VMAT2, and also indicate that there are separate substrate and
      inhibitor binding sites within these transporters. The transporters may allow the
      accumulation of tryptamines within neurons to reach relatively high levels for
      sigma-1 receptor activation and to function as releasable transmitters.

PMID- 19756362
TI  - Arithmetic tasks in different formats and their influence on behavior and brain
      oxygenation as assessed with near-infrared spectroscopy (NIRS): a study involving
      primary and secondary school children.
AB  - This study investigated whether near-infrared spectroscopy (NIRS) can be used to
      measure the processing of arithmetic problems in school children. Another aim was
      to assess whether distinct formats of such problems would lead to different
      neural processing. Two large samples of school children from different age groups
      were examined while calculating or reading arithmetic problems that were either
      presented in numeric or in word format. As expected, we found that, compared to
      reading, calculation resulted in greater average oxygenation in parietal and
      posterior frontal regions. Neither format nor age had a significant effect on
      brain oxygenation. We were able to demonstrate that NIRS measurements can readily
      be conducted with children and in school settings, which is an indication for the
      ecological validity of this measurement technique.

PMID- 19756363
TI  - Methylphenidate treatment increases Na(+), K (+)-ATPase activity in the cerebrum
      of young and adult rats.
AB  - Methylphenidate is a central nervous system stimulant used for the treatment of
      attention-deficit hyperactivity disorder. Na(+), K(+)-ATPase is a membrane-bound
      enzyme necessary to maintain neuronal excitability. Considering that
      methylphenidate effects on central nervous system metabolism are poorly known and
      that Na(+), K(+)-ATPase is essential to normal brain function, the purpose of
      this study was to evaluate the effect of this drug on Na(+), K(+)-ATPase activity
      in the cerebrum of young and adult rats. For acute administration, a single
      injection of methylphenidate (1.0, 2.0, or 10.0 mg/Kg) or saline was given to
      rats on postnatal day 25 or postnatal day 60, in the young and adult groups,
      respectively. For chronic administration, methylphenidate (1.0, 2.0, or 10.0
      mg/Kg) or saline injections were given to young rats starting at postnatal day 25
      once daily for 28 days. In adult rats, the same regimen was performed starting at
      postnatal day 60. Our results showed that acute methylphenidate administration
      increased Na(+), K(+)-ATPase activity in hippocampus, prefrontal cortex, and
      striatum of young and adult rats. In young rats, chronic administration of
      methylphenidate also enhanced Na(+), K(+)-ATPase activity in hippocampus and
      prefrontal cortex, but not in striatum. When tested in adult rats, Na(+), K(+)
      ATPase activity was increased in all cerebral structures studied. The present
      findings suggest that increased Na(+), K(+)-ATPase activity may be associated
      with neuronal excitability caused by methylphenidate.

PMID- 19756364
TI  - Further evidence for the association between attention deficit/hyperactivity
      disorder and the serotonin receptor 1B gene.
AB  - Several evidences suggested that the serotonin 5-HT1B receptor gene (HRT1B) might
      be involved in the susceptibility to attention deficit/hyperactivity disorder
      (ADHD). Prior studies reported excess transmissions of the HRT1B gene 861G allele
      to affected ADHD children and of a haplotype block containing this variant and
      two functional promoter SNPs to probands with ADHD-inattentive subtype. However,
      some investigations did not replicate these findings. Therefore, we tested for
      biased transmissions of haplotypes derived from the 861G > C, -161A > T, and 
      261T > G SNPs from parents to 343 families with ADHD children. We also sought to
      replicate findings from the literature that the association between HTR1B is
      preferentially with ADHD-Inattentive subtype. Using a transmission disequilibrium
      test we found evidence for an excess transmission of haplotype. -261G/-161T/861G
      (P = 0.014) for affected children in the total sample. When the analysis was
      repeated with 143 families with ADHD-Inattentive subtype no significant
      associations were observed. Our results provide additional evidence that HRT1B
      gene may be an important risk factor for the development of ADHD, but this effect
      seems not to be attributable to inattentive cases.

PMID- 19756365
TI  - Accumulation of phosphorylated tyrosine hydroxylase into insoluble protein
      aggregates by inhibition of an ubiquitin-proteasome system in PC12D cells.
AB  - Tyrosine hydroxylase (TH) is a rate-limiting enzyme for the biosynthesis of
      catecholamines including dopamine. The relationship between proteasomal
      dysfunction and the etiology of Parkinson's disease has been suggested, but it is
      unknown if TH protein is affected by proteasomal dysfunctions. Here, we examined
      the effect of inhibition of ubiquitin-proteasomal pathway on biochemical
      characteristics of TH protein in the neuronal cells. Inhibition of 20S or 26S
      proteasome by proteasome inhibitor I, or MG-132 in NGF-differentiated PC12D cells
      induced dot-like immunoreactivities with the anti-(40)Ser-phosphorylated TH (p40
      TH) antibody. These dots were tightly co-localized with ubiquitin and positive to
      Thioflavine-S staining. These dot-like immunoreactivities were not obvious when
      immunostaining was performed against total-TH or choline acetyltransferase.
      Western blotting analysis showed time-dependent increase of p40-TH in the Triton
      insoluble fractions. We also examined the effect of okadaic acid, an inhibitor of
      protein phosphatase 2A, which is a phosphatase acting on p40-TH. Okadaic acid
      increased the amount of insoluble p40-TH. These data suggest that p40-TH is prone
      to be insolubilized and aggregated by dysfunction of an ubiquitin-proteasome
      system in PC12D cells.

PMID- 19756366
TI  - The LRRK2 G2019S mutation as the cause of Parkinson's disease in Ashkenazi Jews.
AB  - Mutations in the leucine rich repeat kinase 2 gene (LRRK2) are recognized as the
      most common cause of genetic Parkinsonism to date. The G2019S mutation has been
      implicated as an important determinant of Parkinson's disease (PD) in both
      Ashkenazi Jewish and North African Arab populations with carrier frequency of
      29.7% among familial and 6% in sporadic Ashkenazi Jewish PD cases. PD patients
      with the G2019S mutation display similar clinical characteristics to patients
      with sporadic PD. While the function of the LRRK2 protein has yet to be fully
      determined, its distribution coincides with brain areas most affected by PD. The
      G2019S mutation is believed to be responsible for up-regulation of LRRK2 kinase
      activity, which may ultimately play a role in neuronal loss. The utility of LRRK2
      G2019S screening in family members of Ashkenazi PD patients is discussed. LRRK2
      G2019S mutation carriers without PD may be an ideal population for the study of
      possible neuroprotective strategies as they become available, and for furthering
      the understanding of the pathogenesis and long-term clinical outcomes of the
      disease.

PMID- 19756367
TI  - Levetiracetam reduces myoclonus in corticobasal degeneration: report of two
      cases.
AB  - Levetiracetam (LEV) has been shown to suppress myoclonus of various origins.
      Corticobasal degeneration (CBD), a progressive neurodegenerative disorder with
      Parkinsonian syndrome, is frequently accompanied by myoclonus. We investigated
      the effect of LEV on myoclonus in two CBD patients. LEV remarkably decreased the
      myoclonic activity in both patients already at 1,500 mg/day dose. This is the
      first report on LEV alleviating myoclonus in CBD. Our data indicate that it might
      be worthwhile to assess this effect in an appropriately designed study.

PMID- 19756368
TI  - Lower CSF HVA and 5-HIAA in bipolar disorder type 1 with a history of childhood
      ADHD.
AB  - Bipolar disorder with childhood attention-deficit hyperactivity disorder (ADHD)
      is a subphenotype characterized by earlier age of onset, more frequent mood
      episodes, more suicide attempts, and more interpersonal violence than pure
      bipolar patients. The aim of this study was to test the biological validity of
      using childhood ADHD to subgroup bipolar disorder. The monoamine metabolites,
      homovanillinic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA) and 3-methoxy-4
      hydroxyphenylglycol (MHPG) were determined in the cerebrospinal fluid (CSF) of 53
      euthymic patients with bipolar disorder type 1, with (N = 17) and without (N =
      36) a history of childhood ADHD. In addition to structured clinical interviews,
      childhood ADHD was assessed by a next of kin using the Autism-Tics, ADHD and
      other comorbidities questionnaire (A-TAC), and by patients themselves using the
      Wender Utah rating scale (WURS-25). Current ADHD symptoms were assessed by the
      Brown attention-deficit disorder scale (Brown ADD). Bipolar patients with
      childhood ADHD had significantly lower CSF concentration (mean +/- SD nmol/l) of
      HVA (89.0 +/- 32.5 vs. 115.8 +/- 47.1, P = 0.039) and 5-HIAA (88.7 +/- 38.5 vs.
      116 +/- 47.9, P = 0.021) than pure bipolar patients. CSF MHPG did not differ
      between the groups. The WURS-25 score correlated negatively with both HVA (r = 
      0.27, P = 0.048) and 5-HIAA (r = -0.30, P = 0.027). Likewise, the Brown ADD total
      score correlated negatively with both HVA (r = -0.34, P = 0.013) and 5-HIAA (r = 
      0.35, P = 0.011). These findings indicate different monoaminergic function in
      patients with and without childhood ADHD in bipolar disorder type 1. This lends
      biological support to the notion that those with childhood ADHD represent a valid
      subphenotype of bipolar disorder.

PMID- 19756369
TI  - Is phosphoadenosine phosphate phosphatase a target of lithium's therapeutic
      effect?
AB  - Lithium, which is approved for treating patients with bipolar disorder, is
      reported to inhibit 3'(2')-phosphoadenosine-5'-phosphate (PAP) phosphatase
      activity. In yeast, deletion of PAP phosphatase results in elevated PAP levels
      and in inhibition of sulfation and of growth. The effect of lithium on PAP
      phosphatase is remarkable for the low Ki (approximately 0.2 mM), suggesting that
      this system would be almost completely shut down in vivo with therapeutic levels
      of 1 mM lithium, thereby elevating PAP levels. To test the hypothesis that
      lithium inhibition of PAP phosphatase is pharmacologically relevant to bipolar
      disorder, we fed rats LiCl for 6 weeks, and assayed brain PAP levels after
      subjecting the brain to high-energy microwaving. We also measured PAP phosphatase
      mRNA and protein levels in frozen brain tissue of lithium-treated mice. Brain
      adenosine phosphates were extracted by trichloroacetic acid and assayed by HPLC
      with a gradient system of two phases. PAP phosphatase mRNA was measured by RT
      PCR, and PAP phosphatase protein was measured by Western blotting. Brain PAP
      levels were below detection limit of 2 nmol/g wet weight, even following lithium
      treatment. Lithium treatment also did not significantly change brain PAP
      phosphatase mRNA or protein levels. These results question the relevance of PAP
      phosphatase to the therapeutic mechanism of lithium. A statistically significant
      25% reduced brain ADP/ATP ratio was found following lithium treatment in line
      with lithium's suggested neuroprotective effects.

PMID- 19756370
TI  - Peripheral cholinoceptor antagonist anisodamine counteracts cholinergic adverse
      effects and facilitates cognitive amelioration of rivastigmine.
AB  - Rivastigmine is a potent acetyl- and butyrylcholinesterase inhibitor widely used
      for cognitive improvement in Alzheimer's disease (AD) therapy. However, dose
      limiting adverse effects restrict its tolerability and clinical outcomes. This
      study explored new combined therapy, in which peripheral cholinergic adverse
      effects and central cognitive amelioration of rivastigmine were differentiated by
      a peripheral cholinoceptor antagonist anisodamine. The results demonstrated that
      rivastigmine (0.75 and 2.0 mg/kg) could significantly reverse the scopolamine
      induced cognitive deficit in mice through passive avoidance test. Nevertheless, a
      high dose of rivastigmine (3.25 mg/kg) would compromise cognitive amelioration
      and produce obvious adverse effects, including hypersalivation, intestinal
      hyperperistalsis and muscle cramp. Interestingly, concomitant administration of
      anisodamine (10 mg/kg) effectively counteracted both the muscarinergic and
      nicotinergic adverse effects, while facilitating cognitive amelioration of
      rivastigmine (3.25 mg/kg). These findings provide an insight into the feasibility
      of combined therapy with cholinesterase inhibitors and peripheral cholinoceptor
      antagonists for the treatment of AD.

PMID- 19756371
TI  - Salvage therapy with gemcitabine, ifosfamide, dexamethasone, and oxaliplatin
      (GIDOX) for B-cell non-Hodgkin's lymphoma: a consortium for improving survival of
      lymphoma (CISL) trial.
AB  - BACKGROUND: We investigated response rates to and toxicities of gemcitabine,
      ifosfamide, dexamethasone, and oxaliplatin (GIDOX) for the treatment of relapsed
      or refractory aggressive B-cell non-Hodgkin lymphoma (NHL). PATIENTS AND METHODS:
      Patients with recurrent or refractory diffuse large B-cell lymphoma or mantle
      cell lymphoma (DLBCL) were eligible for enrollment in this study. Treatment
      consisted of gemcitabine 1,000 mg/m(2) intravenously (i.v.) on Days 1 and 8,
      ifosfamide 2,000 mg/m(2) i.v. on Day 1, dexamethasone 40 mg orally on Days 1-4,
      and oxaliplatin 130 mg/m(2) i.v. on Day 2, every 21 days. The primary goal of
      treatment was to establish a response rate after three cycles. Afterwards,
      patients could proceed to high-dose chemotherapy followed by autologous stem cell
      transplantation (HDC-ASCT) or receive up to six treatment cycles. RESULTS: Twenty
      seven eligible patients were evaluated for toxicity and response. The median age
      of the patients was 54 years (range, 18-75 years), and most had DLBCL. After
      three cycles, there were four CR (15%) and 10 PR (37%) for an overall response
      rate (RR) of 52%. Among a total of 88 GIDOX cycles, grade 3 and 4 neutropenia
      occurred in 33% and 16% of the cycles, respectively. Likewise, grade 3 and 4
      thrombocytopenia occurred in 14% and 16% of the cycles, respectively. Two
      patients (2%) experienced febrile neutropenia, while seven patients (26%)
      proceeded to HDC-ASCT. CONCLUSIONS: GIDOX is an active salvage regimen for
      aggressive B-cell NHL and can be tolerated by patients with acceptable toxicity.

PMID- 19756372
TI  - Justification of the starting dose as the main determinant of accrual time in
      dose-seeking oncology phase 1 trials.
AB  - INTRODUCTION: New drug development is a time- and resource-consuming process.
      Phase 1 trials constitute a major key-step of this development. Shortening the
      accrual time is of major importance. METHODS: 292 published phase-1-trials were
      retrospectively reviewed to establish the determinants of accrual time using Log
      rank test and then Cox Model. RESULTS: Out of 292 trials (1997-2008), only 107
      reports (36%) described the accrual time (median: 20 months, 5-72). Phase-2
      recommended dose was established in 87 studies (81%). Most studies investigated
      regimens including cytotoxic drugs (77%) or molecular targeted therapies (29%).
      Under univariate analysis, two parameters shortened the accrual time: studies
      conducted in USA vs. other places (19 vs. 21 months p = 0.03) and regimen with
      more than 2 dose-escalated drugs (13 vs. 21 months, p = 0.003). One parameter was
      significantly associated with longer accrual time: starting dose justified by
      animal toxicology data vs. previous clinical trials (22 vs. 19 months, p = 0.03).
      Most of parameters did not significantly affect the accrual time: nature of
      investigated drugs, duration of treatment cycle, phase 1 dedicated to specific
      tumoral subtypes, number of centers, method of drug escalation (classical 3+3 vs.
      accelerated titration design), type of increment (modified Fibonacci method vs.
      others) and presence of expansion of cohort at the phase-II-recommended dose. Cox
      model analysis retained one determinant: starting dose justified by animal
      toxicology data: HR = 2.00 [1.45-5.20], p = 0.047. CONCLUSION: Few parameters
      influence the accrual time of dose-escalation phase-1 trials. Real first-in-man
      phase 1 studies based on starting dose estimated from animal toxicological data
      require longer accrual time.

PMID- 19756373
TI  - Preclinical activity of gefitinib in non-keratinizing nasopharyngeal carcinoma
      cell lines and biomarkers of response.
AB  - This study evaluated the preclinical activity and molecular predictors of
      response to gefitinib (Iressa(R), Astra Zeneca Inc, UK) in nasopharyngeal
      carcinoma (NPC). The activity of gefitinib was evaluated in four human NPC cell
      lines--HK1, HONE-1, CNE2, C666-1. A representative gefitinib-sensitive (HK1,
      IC(50) = 250 nM) and gefitinib-resistant cell line (HONE-1, IC(50) > 15 microM)
      were selected and compared for expression of epidermal growth factor receptor
      (EGFR) and related ligands, and activation of downstream proteins. Gefitinib
      induced G1 cycle arrest, apoptosis and inhibited cell invasion more significantly
      in HK1 than HONE-1 cells. HK1 expressed higher levels of p-EGFR, lower p-AKT and
      phospho-signal transducer and activator of transcription 3 (p-STAT3) than other
      cell lines. EGFR gene was found to be amplified in HK1. Gefitinib at IC(50)
      concentrations significantly suppressed EGF-induced activation of p-EGFR, phospho
      mitogen-activated protein kinase (p-MAPK) and p-STAT3, but p-AKT showed
      persistent activation in HK1 and HONE-1 cells. There was no difference in EGFR
      ligand expression between the 4 NPC cell lines. In NPC samples derived from non
      responders to gefitinib, 50% and 60% showed cytoplasmic and nuclear pi-EGFR
      expression, respectively, and 33% showed p-AKT expression. EGFR or KRAS mutations
      were not detected. This study suggests that most NPC cell lines are intrinsically
      resistant to gefitinib (except HK1 cells), and further studies are needed to
      confirm whether EGFR gene amplification and persistent AKT activation may
      influence response to gefitinib in NPC.

PMID- 19756374
TI  - Dysphonia induced by vascular endothelium growth factor/vascular endothelium
      growth factor receptor inhibitors.

PMID- 19756375
TI  - DH9, a novel PPARgamma agonist suppresses the proliferation of ADPKD epithelial
      cells: An association with an inhibition of beta-catenin signaling.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disease that
      exclusively progresses to renal failure. An important target for the treatment of
      ADPKD is to reduce cystic cell proliferation. PPARgamma agonists such as TZDs are
      insulin sensitizing agents that have also been reported to decrease tumor growth.
      Here we tested DH9, a newly synthesized PPARgamma agonist on the proliferation of
      an ADPKD cell line, WT9-12. DH9 showed a potent anti-proliferative activity
      against ADPKD cells. At high concentration, DH9 also induced apoptotic cell
      death. The effect of DH9 on cell proliferation was mediated by a PPARgamma
      independent mechanism. Since DH9 decreased the levels of beta-catenin in cells
      via a GSK3beta mediated degradation pathway, this acts as a mechanism for growth
      inhibition by DH9.

PMID- 19756376
TI  - Bevacizumab for salvage treatment of metastatic breast cancer: a systemic review
      and meta-analysis of randomized controlled trials.
AB  - Although various new agents have been developed for the treatment of patients
      with metastatic breast cancer (MBC), overall survival rates have changed little
      in the last half century. We conducted meta-analysis to verify the clinical
      efficacy of bevacizumab for the salvage treatment of MBC. Event-based hazard
      ratios (HR) with 95% confidence intervals (95% CIs) were derived, and a test of
      heterogeneity was applied. Four studies, with a total of 2,860 patients, met the
      inclusion criteria for analysis. The pooled results of clinical efficacies were:
      HR for progression free survival 0.69 (95% CI, 0.58-0.81, z = 4.54, P <0.001); HR
      for overall survival 0.92 (95% CI, 0.82-1.03, z =1.44, P = 0.15); and HR for the
      clinical objective response rate 1.53 (95% CI, 1.37-1.71, z = 7.37, P < 0.001).
      In terms of overall survival, subgroup analysis demonstrated statistically
      significant improvement for the bevacizumab combination in the initial therapy
      subgroup (HR, 0.878; 95% CI, 0.771-0.999, z = 1.98, P = 0.048). Hypertension and
      proteinura were more common in the bevacizumab combination arm; however, these
      toxicities were managed with therapy. In conclusion, meta-analysis suggested
      benefits of a carefully managed bevacizumab-containing salvage regimen for
      patients with histologically or cytologically confirmed Her-2 negative MBC who
      have not received previous cytotoxic therapy. This treatment could improve both
      progression free survival and overall survival rates.

PMID- 19756377
TI  - Synthesis, characterization and in vitro anti-tumor activities of novel 9-ethyl
      9H-purine derivatives.
AB  - Newer series of 9-ethyl-9H-purine derivatives (EPD) were synthesized and screened
      for their efficacy in inhibiting the proliferation of various tumor cells in
      vitro. We evaluated the effects of EPD against HeLa, SiHa, CaSki (human cervical
      cancer cells), LM8, LM8G7 (murine osteosarcoma cells), OVSAHO and SKOV-3 (human
      ovarian cancer cells). The chemical structures of the EPD were confirmed by (1)H
      NMR and LCMS analyses. The inhibitory effects of EPD were studied by using trypan
      blue exclusion, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      (MTT) and TetraColor One reagents. Furthermore, SAR studies revealed that the
      presence of trifluoromethoxy and trifluromethyl group in 4b and 4g, respectively
      are responsible for the significant activity of the EPD against cervical cancer
      cells and the presence of isopropoxy group in 4f has influence in inhibiting the
      proliferation of osteosarcoma and ovarian cancer cell types.

PMID- 19756378
TI  - Activation and repression of prion protein expression by key  regions of intron
      1.
AB  - Expression of the prion protein is necessary for infection with prion diseases.
      Altered expression levels may play an important role in susceptibility to
      infection. Therefore, understanding the mechanisms that regulate prion protein
      expression is of great importance. It was previously shown that expression of the
      prion protein is to some degree regulated by an alternative promoter within
      intron 1. Studies using GFP and luciferase reporter systems were undertaken to
      determine key sites for the repression and activation of expression of the prion
      protein driven by intron 1. We identified a region within intron 1 sufficient to
      drive prion protein expression. Our findings highlight two potential repressor
      regions. Both regions have binding sites for the known repressor Hes-1. Hes-1
      overexpression caused a dramatic decrease in PrP protein expression.
      Additionally, we have identified Atox-1 as a transcription factor that
      upregulates prion protein expression. These findings clearly indicate that intron
      1 plays a key role in regulation of prion protein expression levels.

PMID- 19756379
TI  - GABA transporter lysine 448: a key residue for tricyclic  antidepressants
      interaction.
AB  - The effects of three tricyclic antidepressants (TCAs) and two serotonin selective
      reuptake inhibitors (SSRIs) have been studied with an electrophysiological
      approach on Xenopus laevis oocytes expressing the rat GABA (gamma-Aminobutyric
      acid) transporter rGAT1. All tested TCAs and SSRIs inhibit the GABA-associated
      current in a dose-dependent way with low but comparable efficacy. The pre-steady
      state and uncoupled currents appear substantially unaffected. The efficacy of
      desipramine, but not of the other drugs, is strongly increased in the lysine
      glutamate or -aspartate mutants K448E and K448D. Comparison of I(max) and
      K(0.5GABA) in the absence and presence of desipramine showed that both parameters
      are reduced by the drug in the wild-type and in the K448E mutant. This suggests
      an uncompetitive inhibition, in which the drug can bind only after the substrate,
      an explanation in agreement with the lack of effects on the pre-steady-state and
      leak currents, and with the known structural data.

PMID- 19756380
TI  - Redox-sensitivity of the dimerization of occludin.
AB  - Occludin is a self-associating transmembrane tight junction protein affected in
      oxidative stress. However, its function is unknown. The cytosolic C-terminal tail
      contains a coiled coil-domain forming dimers contributing to the self
      association. Studying the hypothesis that the self-association is redox
      sensitive, we found that the dimerization of the domain depended on the
      sulfhydryl concentration of the environment in low-millimolar range. Under
      physiological conditions, monomers and dimers were detected. Masking the
      sulfhydryl residues in the domain prevented the dimerization but affected neither
      its helical structure nor cylindric shape. Incubation of cell extracts containing
      full-length occludin with sulfhydryl reagents prevented the dimerization; a
      cysteine/alanine exchange mutant also did not show dimer formation. This
      demonstrates, for the first time, that disulfide bridge formation of the domain
      is involved in the occludin dimerization. It is concluded that the redox
      dependent dimerization of occludin may play a regulatory role in the tight
      junction assembly under physiological and pathological conditions.

PMID- 19756381
TI  - Slug gene expression supports human osteoblast maturation.
AB  - This study aims to define the function of Slug transcription factor in human
      normal osteoblasts (hOBs). To date, Slug is considered exclusively a marker of
      malignancy in bone tissue. Here, we identified, for the first time, a role for
      Slug in hOBs using a knockdown approach. We demonstrated that Slug is positively
      correlated with osteoblast markers, including Runx2, osteopontin, osteocalcin,
      Collagen type 1, Wnt/beta-catenin signaling mediators, and mineral deposition. At
      the same time, Slug silencing potentiates the expression of Sox-9, a factor
      indispensable for chondrogenic development. These data, with the finding that
      Slug is in vivo recruited by the promoters of Runx2 and Sox-9 genes, suggest
      that, in hOBs, Slug may act both as positive and negative transcriptional
      regulator of Runx2 and Sox-9 genes, respectively. In summary, our results support
      the hypothesis that Slug functions as a novel regulator of osteoblast activity
      and may be considered a new factor required for osteoblast maturation.

PMID- 19756382
TI  - Hypoxia, hypoxia-inducible factors (HIF), HIF hydroxylases and oxygen sensing.
AB  - This article outlines the need for a homeostatic response to alterations in
      cellular oxygenation. It describes work on erythropoietin control that led to the
      discovery of the hypoxia-inducible transcription factor (HIF-1) and the parallel
      recognition that this system was responsive to a widespread oxygen-sensing
      mechanism. Subsequently, multiple HIF isoforms have been shown to have
      overlapping but non-redundant functions, controlling expression of genes involved
      in diverse processes such as angiogenesis, vascular tone, metal transport,
      glycolysis, mitochondrial function, cell growth and survival. The major role of
      prolyl and asparaginyl hydroxylation in regulating HIFs is described, as well as
      the identification of PHD1-3 and FIH as the oxygen-sensing enzymes responsible
      for these hydroxylations. Current understanding of other processes that modulate
      overall HIF activity, including influences from other signalling mechanisms such
      as kinases and nitric oxide levels, and the existence of a variety of feedback
      loops are outlined. The effects of some mutations in this pathway are documented
      as is knowledge of other substrates for these enzymes. The importance of PHD1-3
      and FIH, and the large family of 2-oxoglutarate and iron(II)-dependent
      dioxygenases of which they are a part, in biology and medicine are discussed.

PMID- 19756383
TI  - The response of human skeletal muscle tissue to hypoxia.
AB  - Hypoxia refers to environmental or clinical settings that potentially threaten
      tissue oxygen homeostasis. One unique aspect of skeletal muscle is that, in
      addition to hypoxia, oxygen balance in this tissue may be further compromised
      when exercise is superimposed on hypoxia. This review focuses on the cellular and
      molecular responses of human skeletal muscle to acute and chronic hypoxia, with
      emphasis on physical exercise and training. Based on published work, it is
      suggested that hypoxia does not appear to promote angiogenesis or to greatly
      alter oxidative enzymes in skeletal muscle at rest. Although the HIF-1 pathway in
      skeletal muscle is still poorly documented, emerging evidence suggests that
      muscle HIF-1 signaling is only activated to a minor degree by hypoxia. On the
      other hand, combining hypoxia with exercise appears to improve some aspects of
      muscle O(2) transport and/or metabolism.

PMID- 19756384
TI  - Breathing at high altitude.
AB  - Acclimatization to long-term hypoxia takes place at high altitude and allows
      gradual improvement of the ability to tolerate the hypoxic environment. An
      important component of this process is the hypoxic ventilatory acclimatization
      (HVA) that develops over several days. HVA reveals profound cellular and
      neurochemical re-organization occurring both in the peripheral chemoreceptors and
      in the central nervous system (in brainstem respiratory groups). These changes
      lead to an enhanced activity of peripheral chemoreceptor and re-inforce the
      central translation of peripheral inputs to efficient respiratory motor activity
      under the steady low O(2) pressure. We will review the cellular processes
      underlying these changes with a particular emphasis on changes of
      neurotransmitter function and ion channel properties in peripheral
      chemoreceptors, and present evidence that low O(2) level acts directly on
      brainstem nuclei to induce cellular changes contributing to maintain a high tonic
      respiratory drive under chronic hypoxia.

PMID- 19756385
TI  - Erythropoietin modulates the neural control of hypoxic ventilation.
AB  - Numerous factors involved in general homeostasis are able to modulate
      ventilation. Classically, this comprises several kind of molecules, including
      neurotransmitters and steroids that are necessary for fine tuning ventilation
      under different conditions such as sleep, exercise, and acclimatization to high
      altitude. Recently, however, we have found that erythropoietin (Epo), the main
      regulator of red blood cell production, influences both central (brainstem) and
      peripheral (carotid bodies) respiratory centers when the organism is exposed to
      hypoxic conditions. Here, we summarize the effect of Epo on the respiratory
      control in mammals and highlight the potential implication of Epo in the
      ventilatory acclimatization to high altitude, as well as in the several
      respiratory sickness and syndromes occurring at low and high altitude.

PMID- 19756386
TI  - Desmosomal interactome in keratinocytes: a systems biology approach leading to an
      understanding of the pathogenesis of skin disease.
AB  - We provide the first description of the desmosome network in keratinocytes using
      a systems level approach. The desmo-adhesome consists of 59 proteins connected by
      128 direct interactions and forms different functional subnets. Whilst the
      structure appears to be extremely robust against random perturbations, network
      fragmentation analysis suggests that the desmo-adhesome is susceptible to
      targeted attacks. To confirm this prediction, we applied this model to the
      autoimmune disease Pemphigus Vulgaris (PV), a paradigm of external perturbation
      of the desmosome. Our analysis showed that the adaptor protein plakophilin (Pkp)
      3 was in the highest percentile group for both connectivity rate and gene
      expression changes in experimental PV. This observation led us to speculate that
      Pkp3 was crucial in desmosomal remodelling, and therefore we designed the
      experiments to verify this hypothesis. Our data demonstrate that, whilst Pkp3 is
      important in conferring adhesive strength to keratinocytes, it also acts as a
      central molecule mediating cell-cell detachment induced by PV IgG.

PMID- 19756387
TI  - delta-Opioid receptors protect from anoxic disruption of Na+ homeostasis via Na+
      channel regulation.
AB  - Hypoxic/ischemic disruption of ionic homeostasis is a critical trigger of
      neuronal injury/death in the brain. There is, however, no promising strategy
      against such pathophysiologic change to protect the brain from hypoxic/ischemic
      injury. Here, we present a novel finding that activation of delta-opioid
      receptors (DOR) reduced anoxic Na+ influx in the mouse cortex, which was
      completely blocked by DOR antagonism with naltrindole. Furthermore, we co
      expressed DOR and Na+ channels in Xenopus oocytes and showed that DOR expression
      and activation indeed play an inhibitory role in Na+ channel regulation by
      decreasing the amplitude of sodium currents and increasing activation threshold
      of Na+ channels. Our results suggest that DOR protects from anoxic disruption of
      Na+ homeostasis via Na+ channel regulation. These data may potentially have
      significant impacts on understanding the intrinsic mechanism of neuronal
      responses to stress and provide clues for better solutions of hypoxic/ischemic
      encephalopathy, and for the exploration of acupuncture mechanism since
      acupuncture activates opioid system.

PMID- 19756389
TI  - Cell death and stress signaling in glycogen storage disease type I.
AB  - Cell death has been traditionally classified in apoptosis and necrosis.
      Apoptosis, known as programmed cell death, is an active form of cell death
      mechanism that is tightly regulated by multiple cellular signaling pathways and
      requires ATP for its appropriate process. Apoptotic death plays essential roles
      for successful development and maintenance of normal cellular homeostasis in
      mammalian. In contrast to apoptosis, necrosis is classically considered as a
      passive cell death process that occurs rather by accident in disastrous
      conditions, is not required for energy and eventually induces inflammation.
      Regardless of different characteristics between apoptosis and necrosis, it has
      been well defined that both are responsible for a wide range of human diseases.
      Glycogen storage disease type I (GSD-I) is a kind of human genetic disorders and
      is caused by the deficiency of a microsomal protein, glucose-6-phosphatase-alpha
      (G6Pase-alpha) or glucose-6-phosphate transporter (G6PT) responsible for glucose
      homeostasis, leading to GSD-Ia or GSD-Ib, respectively. This review summarizes
      cell deaths in GSD-I and mostly focuses on current knowledge of the neutrophil
      apoptosis in GSD-Ib based upon ER stress and redox signaling.

PMID- 19756388
TI  - Neuroscience of alcoholism: molecular and cellular mechanisms.
AB  - Alcohol use and abuse appear to be related to neuroadaptive changes at
      functional, neurochemical, and structural levels. Acute and chronic ethanol
      exposure have been shown to modulate function of the activity-dependent gene
      transcription factor, cAMP-responsive element binding (CREB) protein in the
      brain, which may be associated with the development of alcoholism. Study of the
      downstream effectors of CREB have identified several important CREB-related
      genes, such as neuropeptide Y, brain-derived neurotrophic factor, activity
      regulated cytoskeleton-associated protein, and corticotrophin-releasing factor,
      that may play a crucial role in the behavioral effects of ethanol and molecular
      changes in the specific neurocircuitry that underlie both alcohol addiction and a
      genetic predisposition to alcoholism. Brain chromatin remodeling due to histone
      covalent modifications may also be involved in mediating the behavioral effects
      and neuroadaptive changes that occur during ethanol exposure. This review
      outlines progressive neuroscience research into molecular and epigenetic
      mechanisms of alcoholism.

PMID- 19756390
TI  - Complete mitochondrial genome of brown marmorated stink bug Halyomorpha halys
      (Hemiptera: Pentatomidae), and phylogenetic relationships of hemipteran
      suborders.
AB  - The newly sequenced complete mitochondrial genome of the brown marmorated stink
      bug, Halyomorpha halys (Stal) (Hemiptera: Pentatomidae), is a circular molecule
      of 16,518 bp with a total A+T content of 76.4% and two extensive repeat regions
      in A+T rich region. Nucleotide composition and codon usage of H. halys are about
      average when compared with values observed in 19 other published hemipteran
      mitochondrial genomes. Phylogenetic analyses using these 20 hemipteran
      mitochondrial genomes support the currently accepted hypothesis that suborders
      Heteroptera and Auchenorrhyncha form a monophyletic group. The mitochondrial gene
      arrangements of the 20 genomes=are also consistent with our results.

PMID- 19756391
TI  - C. elegans behavior of preference choice on bacterial food.
AB  - Caenorhabditis elegans is a free living soil nematode and thus in its natural
      habitat, C. elegans encounters many different species of soil bacteria. Although
      some soil bacteria may be excellent sources of nutrition for the worm, others may
      be pathogenic. Thus, we undertook a study to understand how C. elegans can
      identify their preferred food using a simple behavioral assay. We found that
      there are various species of soil bacteria that C. elegans prefers in comparison
      to the standard laboratory E. coli strain OP50. In particular, two bacterial
      strains, Bacillus mycoides and Bacillus soli, were preferred strains.
      Interestingly, the sole feeding of these bacteria to wild type animals results in
      extended lifespan through the activation of the autophagic process. Further
      studies will be required to understand the precise mechanism controlling the
      behavior of identification and selection of food in C. elegans.

PMID- 19756392
TI  - Silibinin inhibits osteoclast differentiation mediated by TNF family members.
AB  - Silibinin is a polyphenolic flavonoid compound isolated from milk thistle
      (Silybum marianum), with known hepatoprotective, anticarcinogenic, and
      antioxidant effects. Herein, we show that silibinin inhibits receptor activator
      of NF-kappaB ligand (RANKL)-induced osteoclastogenesis from RAW264.7 cells as
      well as from bone marrow-derived monocyte/macrophage cells in a dose-dependent
      manner. Silibinin has no effect on the expression of RANKL or the soluble RANKL
      decoy receptor osteoprotegerin (OPG) in osteoblasts. However, we demonstrate that
      silibinin can block the activation of NF-kappaB, c-Jun N-terminal kinase (JNK),
      p38 mitogen-activated protein (MAP) kinase, and extracellular signal-regulated
      kinase (ERK) in osteoclast precursors in response to RANKL. Furthermore,
      silibinin attenuates the induction of nuclear factor of activated T cells (NFAT)
      c1 and osteoclast-associated receptor (OSCAR) expression during RANKL-induced
      osteoclastogenesis. We demonstrate that silibinin can inhibit TNF-alpha-induced
      osteoclastogenesis as well as the expression of NFATc1 and OSCAR. Taken together,
      our results indicate that silibinin has the potential to inhibit osteoclast
      formation by attenuating the downstream signaling cascades associated with RANKL
      and TNF-alpha.

PMID- 19756393
TI  - A computational approach for the classification of protein tyrosine kinases.
AB  - Protein tyrosine kinases (PTKs) play a central role in the modulation of a wide
      variety of cellular events such as differentiation, proliferation and metabolism,
      and their unregulated activation can lead to various diseases including cancer
      and diabetes. PTKs represent a diverse family of proteins including both receptor
      tyrosine kinases (RTKs) and non-receptor tyrosine kinases (NRTKs). Due to the
      diversity and important cellular roles of PTKs, accurate classification methods
      are required to better understand and differentiate different PTKs. In addition,
      PTKs have become important targets for drugs, providing a further need to develop
      novel methods to accurately classify this set of important biological molecules.
      Here, we introduce a novel statistical model for the classification of PTKs that
      is based on their structural features. The approach allows for both the
      recognition of PTKs and the classification of RTKs into their subfamilies. This
      novel approach had an overall accuracy of 98.5% for the identification of PTKs,
      and 99.3% for the classification of RTKs.

PMID- 19756394
TI  - The effector functions of mature T lymphocytes are impaired in transgenic mice
      expressing the SH2 domain of TSAd/Lad.
AB  - TSAd/Lad is a T cell adaptor molecule involved in p56(lck)-mediated T cell
      activation. To investigate the functions of TSAd in T cells, we generated
      transgenic (TG) mice expressing the SH2 domain of TSAd (TSAd-SH2) under the
      control of the p56(lck) proximal promoter. In T cells from TSAd-SH2 TG mice, T
      cell receptor (TCR)-mediated early signaling events, such as Ca(2+) flux and ERK
      activation, were normal; however, late activation events, such as IL-2 production
      and proliferation, were significantly reduced. Moreover, TCR-induced cell
      adhesion to extracellular matrix (ECM) proteins and migration through ECM
      proteins were defective in T cells from TSAd-SH2 TG mice. Furthermore, the
      contact hypersensitivity (CHS) reaction, an inflammatory response mainly mediated
      by T helper 1 (Th1) cells, was inhibited in TSAd-SH2 TG mice. Taken together,
      these results show that TSAd, particularly the SH2 domain of TSAd, is essential
      for the effector functions of T cells.

PMID- 19756395
TI  - Proteomic analysis of the triglyceride-rich lipoprotein-laden foam cells.
AB  - In hypertriglyceridaemic individuals, atherosclerogenesis is associated with the
      increased concentrations of very low density lipoprotein (VLDL) and VLDL
      associated remnant particles. In vitro studies have suggested that VLDL induces
      foam cells formation. To reveal the changes of the proteins expression in the
      process of foam cells formation induced by VLDL, we performed a proteomic
      analysis of the foam cells based on the stimulation of differentiated THP-1 cells
      with VLDL. Using two-dimensional gel electrophoresis (2-DE) and matrix-assisted
      laser-desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS)
      analysis, 14 differentially expressed proteins, containing 8 up-regulated
      proteins and 6 down-regulated proteins were identified. The proteins are involved
      in energy metabolism, oxidative stress, cell growth, differentiation and
      apoptosis, such as adipose differentiation-related protein (ADRP), enolase,
      S100A11, heat shock protein 27 and so on. In addition, the expression of some
      selected proteins was confirmed by Western blot and RT-PCR analysis. The results
      suggest that VLDL not only induces lipid accumulation, but also brings about foam
      cells diverse characteristics by altering the expression of various proteins.

PMID- 19756396
TI  - Involvement of Ca2+/calmodulin kinase II (CaMK II) in genistein-induced
      potentiation of leucine/glutamine-stimulated insulin secretion.
AB  - Genistein has been reported to potentiate glucose-stimulated insulin secretion
      (GSIS). Inhibitory activity on tyrosine kinase or activation of protein kinase A
      (PKA) was shown to play a role in the genistein-induced potentiation effect on
      GSIS. The aim of the present study was to elucidate the mechanism of genistein
      induced potentiation of insulin secretion. Genistein augmented insulin secretion
      in INS-1 cells stimulated by various energy-generating nutrients such as glucose,
      pyruvate, or leucine/glutamine (Leu/Gln), but not the secretion stimulated by
      depolarizing agents such as KCl and tolbutamide, or Ca(2+) channel opener Bay
      K8644. Genistein at a concentration of 50 MUM showed a maximum potentiation
      effect on Leu/Gln-stimulated insulin secretion, but this was not sufficient to
      inhibit the activity of tyrosine kinase. Inhibitor studies as well as
      immunoblotting analysis demonstrated that activation of PKA was little involved
      in genistein-induced potentiation of Leu/Gln-stimulated insulin secretion. On the
      other hand, all the inhibitors of Ca(2+)/calmodulin kinase II tested,
      significantly diminished genistein-induced potentiation. Genistein also elevated
      the levels of [Ca(2+)]i and phospho-CaMK II. Furthermore, genistein augmented
      Leu/Gln-stimulated insulin secretion in CaMK II-overexpressing INS-1 cells. These
      data suggest that the activation of CaMK II played a role in genistein-induced
      potentiation of insulin secretion.

PMID- 19756397
TI  - Important residue (G46) in erythroid spectrin tetramer formation.
AB  - Spectrin tetramerization is important for the erythrocyte to maintain its unique
      shape, elasticity and deformability. We used recombinant model proteins to show
      the importance of one residue (G46) in the erythroid alpha-spectrin junction
      region that affects spectrin tetramer formation. The G46 residue in the erythroid
      spectrin N-terminal junction region is the only residue that differs from that in
      non-erythroid spectrin. The corresponding residue is R37. We believe that this
      difference may be, at least in part, responsible for the 15-fold difference in
      the equilibrium constants of erythroid and non-erythroid tetramer formation. In
      this study, we replaced the Gly residue with Ala, Arg or Glu residues in an
      erythroid alpha-spectrin model protein to give G46A, G46R or G46E, respectively.
      We found that their association affinities with a beta-spectrin model protein
      were quite different from each other. G46R exhibited a 10-fold increase and G46E
      exhibited a 16-fold decrease, whereas G46A showed little difference, when
      compared with the wild type. The thermal and urea denaturation experiments showed
      insignificant structural change in G46R. Thus, the differences in affinity were
      due to differences in local, specific interactions, rather than conformational
      differences in these variants. An intra-helical salt bridge in G46R may stabilize
      the partial domain single helix in alpha-spectrin, Helix C', to allow a more
      stable helical bundling in the alphabeta complex in spectrin tetramers. These
      results not only showed the importance of residue G46 in erythroid alpha
      spectrin, but also provided insights toward the differences in association
      affinity between erythroid and non-erythroid spectrin to form spectrin tetramers.

PMID- 19756398
TI  - Yoga and qigong in the psychological prevention of mental health disorders: a
      conceptual synthesis.
AB  - The study proposes to explore two alternative medicine therapies-qigong and yoga
      for balancing the essential duo of holistic mind-body and consequently offer a
      solution for stress, uncertainty, anxiety and depression. Qualitative research
      methods have been used to create a conceptual synthesis of yoga and qigong. It is
      suggested that an increased sense of control is the interface between these two
      modalities. This conceptual congruence of qigong and yoga is thought to be a
      selective, curative method, a prescription for ideal living and a ground of human
      essence existence. Furthermore, this essence is thought to enhance the mind's
      self-regulatory processes and prevent mental health disorders. The two
      alternative therapies can prevent mental health disorders such as anxiety,
      depression and, minimize mental health disruptions such as stress and poor
      quality of life. It is suggested that patients and/or clients can benefit from
      this fusion.

PMID- 19756399
TI  - Antioxidant responses of wheat seedlings to exogenous selenium supply under
      enhanced ultraviolet-B.
AB  - The paper reports the effects of selenium (Se) supply on growth and antioxidant
      traits of wheat (Triticum aestivum L. cv Han NO.7086) seedlings exposed to
      enhanced ultraviolet-B (UV-B) stress. Antioxidant responses of seedlings were
      different depending on the Se concentration. Compared with the control, the lower
      amount used (0.5 mg Se kg(-1) soil) had no significant effect on biomass
      accumulation. The treatments with 1.0, 2.0, and 3.0 mg Se kg(-1) promoted biomass
      accumulation of wheat seedlings, and the increased amount in biomass was the most
      at 1.0 mg Se kg(-1) treatment. Se treatments with 1.0, 2.0, and 3.0 mg kg(-1)
      also significantly increased activities of peroxidase (POD) and superoxide
      dismutase (SOD) and reduced the rate of superoxide radical (O (2) (-) )
      production and malondialdehyde (MDA) content of wheat seedlings. In addition,
      anthocyanins and phenolic compounds content in wheat seedlings evidently
      increased by the treatments with 1.0 and 2.0 mg Se kg(-1). The lower Se treatment
      had no significant effect on MDA content, although it increased activities of
      antioxidant enzymes (POD, SOD, and catalase activities) and reduced the rate of O
      (2) (-) production in wheat seedlings. These results suggest that optimal Se
      supply is favorable for the growth of wheat seedlings and that optimal Se supply
      can reduce oxidative stress of seedlings under enhanced UV-B radiation.

PMID- 19756400
TI  - Effect of 3-(1H-Pyrrol-2-yl)-1H-indazole on the antioxidant status of rats.
AB  - The influence of injection periods of 3-(1H-pyrrol-2-yl)-1H-indazole regarding
      vitamins A, E, C, selenium (Se), malondialdehyde (MDA) levels, and glutathione
      peroxidase (GSH-Px) activity in rats has been investigated. The substance was
      given by subcutaneous injection at 20 mg/kg every other day for a total of 15
      injections. At the end of the treatment, Se levels in serum were determined by
      fluorimetry, and those of vitamins A, E, C, and malondialdehyde in serum, liver,
      and kidney were determined by high-performance liquid chromatography. GSH-Px
      activities in erythrocytes were determined spectrophotometrically. Vitamins A, E,
      C, and Se levels were generally lower than in the controls, while GSH-Px activity
      at the third injection period was maximally increased, with the activities after
      the other injection periods being higher than in the control group. In addition,
      vitamins A, E, and C levels were generally lower than the control groups, while
      serum, liver, and kidney MDA levels gradually increased depending on injection
      periods. On the other hand, GSH-Px activity was higher than in the control group.
      Thus, the results show that while vitamins A, E, C, and Se levels decreased, MDA
      levels and GSH-Px activities increased after administration of 3-(1H-pyrrol-2-yl)
      1H-indazole to the rats. These findings might be related to the increased amount
      of free radicals caused by 3-(1H-pyrrol-2-yl)-1H-indazole injection.

PMID- 19756401
TI  - Effects of parenteral supply of iron on RBC parameters, performance, and health
      in neonatal dairy calves.
AB  - The present study was designed to evaluate the effects of parenteral iron on red
      blood cell parameters, performance, and health in dairy Holstein calves. Twenty
      neonatal calves were equally divided at random into two groups, one of which
      served as controls. Care was taken to ensure homogeneity of sex, age, and general
      health status of the animals. The controls received a normal diet and water ad
      libitum, while the study animals were injected with 1 g iron as Fe-dextran 2 days
      after birth. A daily record was kept of the calves' weight and growth parameters.
      At periods of 24-48 h after birth and at 14, 28, and 42 days of age, jugular
      blood was drawn from all the experimental and control animals to measure the
      packed cell volume, red blood count, hemoglobin, mean corpuscular hemoglobin,
      mean corpuscular hemoglobin concentration, and iron levels. At the start of the
      experiments, there were no significant differences between these parameters
      between the two study groups (p > 0.05). With time, significant differences were
      seen between most of the values measured (p < 0.05) except for the mean
      corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and iron
      level. Significant differences were seen for total weight gain and mean daily
      weight gain, which were higher in the iron-supplemented group (p < 0.05).

PMID- 19756402
TI  - Histomorphometric and microchemical characterization of maturing dental enamel in
      rats fed a boron-deficient diet.
AB  - Few reports are available in the literature on enamel formation under nutritional
      deficiencies. Thus, we performed a study to determine the effects of boron (B)
      deficiency on the maturing dental enamel, employing the rat continuously erupting
      incisor as the experimental model. Male Wistar rats, 21 days old, were used
      throughout. They were divided into two groups, each containing ten animals: +B
      (adequate; 3-mg B/kg diet) and -B (boron deficient; 0.07-mg B/kg diet). The
      animals were maintained on their respective diets for 14 days and then
      euthanized. The mandibles were resected, fixed, and processed for embedding in
      paraffin and/or methyl methacrylate. Oriented histological sections of the
      continuously erupting incisor were obtained at the level of the mesial root of
      the first molar, allowing access to the maturation zone of the developing enamel.
      Dietary treatment did not affect food intake and body weight. Histomorphometric
      evaluation using undecalcified sections showed a reduction in enamel thickness
      (hypoplasia), whereas microchemical characterization by energy-dispersive X-ray
      spectrometry did not reveal alterations in enamel mineralization.

PMID- 19756403
TI  - Analysis of magnesium contents in commonly consumed foods and evaluation of its
      daily intake in Korean independent-living subjects.
AB  - Magnesium, an element involved in a variety of biochemical and physiological
      processes in the human body, is closely linked to maintaining health and
      preventing disease. Even so, studies on the status of magnesium intake have never
      been conducted sufficiently since only recently a dietary reference intake value
      was proposed, and data on magnesium contents in food items have always been
      insufficient. Therefore, in this study, we selected 366 food items commonly
      consumed by Korean people and then analyzed their magnesium content with
      inductively coupled plasma atomic emission spectroscopy. With these results, we
      evaluated daily magnesium intake in 239 healthy adult males and females. Using
      these 366 values based on magnesium content measurements, we evaluated the status
      of magnesium intake by our participants and found that the average daily
      magnesium intake was 279.2 mg, 90.4% of the recommended intake (RI). The results
      also showed that the magnesium intake by 54.8% of the subjects was lower than the
      estimated average requirement. In addition to this, the magnesium intake by 45.2%
      of the cohort was less than 75% of the RI. As such, a high percentage of the
      subjects showed inappropriate magnesium intake.

PMID- 19756404
TI  - Association between zinc, copper, and iron concentrations in breast milk and
      growth of healthy infants in Tabriz, Iran.
AB  - The aims of this study were to determine the effect of breast milk zinc, copper,
      and iron concentrations on infants' growth and their possible correlations with
      maternal dietary intake. Milk samples and information on food intake were
      collected from 182 lactating women. Concentrations of zinc, copper, and iron in
      milk were analyzed using atomic absorption spectrophotometry. The infant's weight
      for age Z-score (WAZ) and height for age Z-score (HAZ) were calculated. The mean
      milk zinc, copper, and iron concentrations were 1.85 +/- 0.5, 0.53 +/- 0.3, and
      0.85 +/- 0.2 mg/l, respectively. Only zinc mean level was lower than the
      recommended range. Association between zinc, copper, and iron concentrations of
      milk and WAZ or HAZ of infants were not significant. However, the WAZ of infants
      whose mothers' milk zinc was more than 2 mg/l was significantly (P < 0.039)
      higher than for others. The mean dietary zinc (5.31 +/- 2.3 mg/day) and copper
      (1.16 +/- 0.7 mg/day) intake of mothers was significantly less than the required
      daily intake (RDA) recommendations (P < 0.05). The mean dietary iron intake (11.8
      +/- 8.2 mg/day) was significantly higher than RDA recommendation (P < 0.001). No
      significant association was found between maternal mean dietary zinc, copper, and
      iron intakes with their concentrations in milk. Dietary consultation or/and zinc
      supplementation is suggested for lactating women and infants.

PMID- 19756405
TI  - Application of factorial design and box-behnken matrix in the optimization of a
      magnetic nanoparticles procedure for copper determination in water and biological
      samples.
AB  - This study describes the development by response surface methodology (RSM) of a
      procedure for copper determination by inductively coupled plasma optical emission
      spectrometry (ICP-OES) in water and biological samples after extraction by
      magnetic nanoparticles. Four variables such as, pH of solution, amount of
      extractant, amount of nanoparticles, and time were regarded as factors in the
      optimization study. Results of the two-level full factorial design (2(4)) based
      on an analysis of variance demonstrated that only the pH, amount of extractant
      (E), and amount of nanoparticles (N) were statistically significant. Optimal
      conditions for the extraction of copper samples were obtained by using Box
      Behnken design. Optimum conditions were 5.1, 7.2 mg, and 9.6 mg, for pH of
      solution, amount of nanoparticles, and amount of extractant, respectively. Under
      the optimized experimental conditions, the detection limit of the proposed method
      followed by ICP-OES was found to be 0.9 microg L(-1). The method was applied to
      the determination of copper in water and biological samples.

PMID- 19756406
TI  - Study of response of thymic and submaxillary lymph node lymphocytes to
      administration of lead by different routes.
AB  - A number of studies have reported that heavy metals are not only toxic for the
      organism but they may modulate immune responses. In the current study, the effect
      of 4-week administration of 200 ppm of PbAc(2), using different routes of
      administration (orally and intraperitoneal injection), on lymphatic organs was
      evaluated. In the thymus, the number of lymphocyte cells and the cellularity
      diminished significantly for both routes of treatment. Regarding the submaxillary
      lymph nodes, no significant variations took place. Cell-mediated immune response
      is commonly evaluated by cell proliferation assays. Mitogens are known to induce
      a vigorous proliferative response in lymphoid cells from mammals. An increase in
      the proliferation of T lymphocytes stimulated by concanavalin A and the
      proliferation of B lymphocytes stimulated with lipopolysaccharides was found in
      thymus for both routes of administration, whereas in the lymph nodes, there was a
      decrease in proliferation of T lymphocytes. Furthermore, lead administration by
      intraperitoneal route caused an effect on B and T lymphocyte subpopulations.
      Thus, there was an increase in B+ cells and a decrease in T+ cells. Regarding
      CD4+ and CD8+ T cells, there were only variations, concretely a drop in both
      subpopulations, in lymph nodes when lead was administered intraperitoneally. It
      is important to emphasize that an increase in apoptosis was found in this tissue.
      At the histological level, evident alterations were described in thymus both for
      the oral and for the intraperitoneal route. Therefore, it is possible to show
      that lead administered by both routes generated effects on an immunological
      level.

PMID- 19756407
TI  - Oral transgenic plant-based vaccine for hepatitis B.
AB  - In addition to improving vaccine formulations in order to elicit robust and long
      lasting immune responses, there is also an increasing need for improving the
      manner in which these vaccines are delivered. As most current vaccines are
      administered by injection by a health care giver, there is the ever-present
      danger of needlestick injuries. Therefore, needle-free vaccinations are a viable
      option toward limiting needle-associated injuries and additionally increasing
      compliance with vaccination schedules, as both children and adults have an
      aversion to injections. Noninvasive methods of vaccination will also facilitate
      speed of vaccine delivery and likely also reduce cost, both important factors for
      health care in developing countries. One alternative to current injectable
      immunizations is orally delivered vaccines. A specific approach that we and
      others are evaluating is the use of transgenic plant tissue that expresses
      vaccine antigens for oral immunization. Herein, we review the development of an
      oral HBV vaccine expressed in transgenic potato tubers and the immune responses
      generated in human subjects given this novel vaccine.

PMID- 19756408
TI  - A multi-functional role of interferon regulatory factor-8 in solid tumor and
      myeloid cell biology.
AB  - Understanding mechanisms of tumor escape are critically important not only to
      improving our knowledge of cancer biology, but also for the overall development
      of more effective anti-neoplastic therapies. Our laboratory focuses on mechanisms
      of apoptotic resistance, with emphasis on Fas loss of function as an important
      determinant of tumor progression. Our work in solid tumor systems has led to the
      identification of interferon regulatory factor-8 (IRF-8) as a differentially
      expressed gene important for tumor cell response to cytotoxicity, including Fas
      mediated apoptosis and host-anti-tumor immunosurveillance mechanisms. Although
      IRF-8 was originally identified in the regulation of normal and neoplastic
      myeloid cell development, these findings revealed a new functional role for IRF-8
      in non-hematopoietic malignancies and establish a molecular basis for its
      potential manipulation during cancer therapy.

PMID- 19756409
TI  - Tumor-mediated inhibition of dendritic cell differentiation is mediated by down
      regulation of protein kinase C beta II expression.
AB  - Tumor-mediated immune suppression occurs through multiple mechanisms, including
      dysregulation of dendritic cell differentiation. This block in differentiation
      results in fewer dendritic cells and an accumulation of immunosuppressive myeloid
      derived suppressor cells and is thought to contribute to tumor outgrowth and to
      act as an impediment to successful anti-cancer immunotherapy. Tumor-mediated
      myeloid dysregulation is known to be Stat3 dependent; however, the molecular
      mechanism of this Stat3 signaling remains poorly defined. We have previously
      shown that PKC betaII is required for dendritic cell differentiation. Here, we
      describe our finding that tumors mediate both Stat3 activation and PKC betaII
      down regulation in DC progenitor cells, a process mimicked by the expression of a
      constitutive active Stat3 mutant. This demonstrates that tumor-mediated myeloid
      dysregulation may be mediated by Stat3- induced PKC betaII down regulation.

PMID- 19756410
TI  - Diverse immune mechanisms may contribute to the survival benefit seen in cancer
      patients receiving hyperthermia.
AB  - There is increasing documentation of significant survival benefits achieved in
      cancer patients treated with hyperthermia in combination with radiation and/or
      chemotherapy. Most evidence collected regarding the mechanisms by which
      hyperthermia positively influences tumor control has centered on in vitro data
      showing the ability of heat shock temperatures (usually above 42 degrees C) to
      result in radio- or chemosensitization. However, these high temperatures are
      difficult to achieve in vivo, and new thermometry data in patients reveal that
      much of the tumor and surrounding region is only heated to 40-41 degrees C or
      less as a result of vascular drainage from the target zone of the heated tumor.
      Thus, there is now a growing appreciation of a role for mild hyperthermia in the
      stimulation of various arms of the immune system in contributing to long term
      protection from tumor growth. Indeed, a review of recent literature suggests the
      existence of an array of thermally sensitive functions which may exist naturally
      to help the organism to establish a new "set point" of immune responsiveness
      during fever. This review summarizes recent literature identifying complex
      effects of temperature on immune cells and potential cellular mechanisms by which
      increased temperature may enhance immune surveillance.

PMID- 19756411
TI  - Intermittent high glucose stimulate MCP-l, IL-18, and PAI-1, but inhibit
      adiponectin expression and secretion in adipocytes dependent of ROS.
AB  - Elevated circulating concentrations of interleukin-18 (IL-18), monocyte
      chemoattractant protein-1 (MCP-1), and plasminogen activator inhibitor-1 (PAI-1)
      and decrease of adiponectin are associated with obesity-related diseases. The
      mechanism that mediates the aberrant production of the adipokines remains poorly
      understood. The aim of this study was to investigate the effect of intermittent
      high glucose on the expression of IL-18, MCP-1, and PAI-1 and adiponectin in 3T3
      L1 adipocytes. 3T3-L1 adipocytes were incubated for 24 h in media containing
      different glucose concentrations: 5 mmol/l, 20 mmol/l and a daily alternating 5
      or 20 mmol/l glucose, with or without the addition of1.0 mmol/l N-acetylcysteine
      (NAC). The expression and secretion of IL-18, MCP-1, PAI-1, and adiponectin were
      determined by real-time RT-PCR and ELISA, respectively.The production of reactive
      oxygen species (ROS) and 8-hydroxydeoxyguanosine(8-OHdG) were measured. Stable
      high glucose significantly increased expression and secretion of IL-18, MCP-1,
      and PAI-1, and reduced adiponectin expression and secretion compared to normal
      glucose conditions.These effects were significantly greater under intermittent
      high glucose conditions compared to stable high glucose. The level of ROS and 8
      OHdG were significantly elevated under both intermittent and stable high glucose
      conditions, the effect being greater under intermittent high glucose. The
      intermittent glucose was more effective in triggering the generation of ROS than
      stable high glucose. The adding of the NAC, aspecific pharmacological inhibitor
      of ROS, normalized the expression of these adipokines and the levels of ROS and 8
      OHdG under both stable and intermittent glucose conditions.Intermittent high
      glucose induces a greater aberrant production of key adipokines than stable high
      glucose, and this effect seems to be related to over-production of ROS.

PMID- 19756412
TI  - Marine diatom, Navicula sp. strain JPCC DA0580 and marine green alga, Chlorella
      sp. strain NKG400014 as potential sources for biodiesel production.
AB  - Marine diatom, strain JPCC DA0580, and marine green microalga strain NKG400014
      were selected as high neutral lipid-producers from marine microalgal culture
      collection toward biodiesel production. These strains were tentatively identified
      as Navicula sp. and Chlorella sp., respectively, by 18S rDNA analysis. Growth and
      lipid accumulation conditions of both strains were analyzed by changing nutrient
      concentrations in growth media and initial illuminance intensity. The highest
      productivity of fatty acid methyl ester (FAME) reached to 154 mg/L/week for
      NKG400014 and 185 mg/L/week for JPCC DA0580. Gas chromatography/mass spectrometry
      analysis indicates that FAME fraction from NKG400014 mainly contained 9-12-15
      octadecatrienoate (C18:3) and that from JPCC DA0580 mainly contained methyl
      palmitate (C16:0) and methyl palmitoleate (C16:1). Furthermore, calorimetric
      analysis revealed that the energy content of strain was 4,233 +/- 55 kcal/kg
      (i.e., 15.9 +/- 0.2 MJ/kg) for NKG400014 and 6,423 +/- 139 kcal/mg (i.e., 26.9 +/
      0.6 MJ/kg) for JPCC DA0580, respectively. The value from JPCC DA0580 was
      equivalent to that of coal. The strains NKG400014 and JPCC DA0580 will become a
      promising resource that can grow as dominant species in the open ocean toward
      production of both liquid and solid biofuels.

PMID- 19756413
TI  - Rational approaches for drug designing against leishmaniasis.
AB  - Leishmaniasis has been ignored for many years mainly because it plagues remote
      and poor areas. However, recently, it has drawn attention of several
      investigators, and active research is going on for antileishmanial drug
      discovery. The current available drugs have high failure rates and significant
      side effects. Recently, liposomal preparations of amphotericin B are available
      and have proved to be a better drug, but they are very expensive. Miltefosine is
      one of the few orally administered drugs that are effective against Leishmania.
      However, it has exhibited teratogenicity, hence, should not be administered to
      pregnant women. Thus, the search for novel and improved antileishmanial drugs
      continue. A rational approach to design and develop new antileishmanials can be
      to identify several metabolic and biochemical differences between host and
      parasite that can be exploited as drug target. Moreover, many natural products
      also have significant antileishmanial activity and are yet to be exploited. In
      the current review, we aim to bring together various drug targets of Leishmania,
      recent development in the field, future prospects, and hope in the area.

PMID- 19756415
TI  - A combination povidone-iodine 0.4%/dexamethasone 0.1% ophthalmic suspension in
      the treatment of adenoviral conjunctivitis.
AB  - INTRODUCTION: The objective of this pilot study was to determine the preliminary
      efficacy of a novel ophthalmic suspension containing povidone-iodine 0.4% and
      dexamethasone 0.1% in the treatment of adenoviral conjunctivitis. METHODS: A
      prospective, open-label, single-armed, phase II clinical trial in humans.
      Eligible patients with the clinical signs and symptoms of acute conjunctivitis
      who tested positive for adenoviral antigen by Rapid Pathogen Screening (RPS)
      Adeno Detector were enrolled in a single treatment arm consisting of a
      combination povidone-iodine 0.4%/dexamethasone 0.1% sterile ophthalmic suspension
      given four times daily for a minimum of 5 days. RPS Adeno Detector testing was
      performed at baseline and at each follow-up visit along with ocular fluid
      sampling by conjunctival swabs. Subsequent analysis performed on all swabs
      included both adenoviral titer by quantitative polymerase chain reaction (qPCR)
      and cell culture with confirmatory immunofluorescence (CC-IFA). The primary
      endpoint was clinical resolution of conjunctival injection and discharge.
      Secondary measures included reduction of qPCR titers and eradication of
      infectious virus as determined by CC-IFA. RESULTS: A total of nine eyes of six
      patients with clinical signs and symptoms of acute viral conjunctivitis and a
      positive RPS Adeno Detector test result were enrolled in the study. In eight/nine
      eyes enrolled in the study, clinical resolution was observed by day 3 or day 4.
      In six/six eyes with detectable adenovirus by qPCR, significant reduction in
      viral titer was seen by day 3, day 4, or day 5. In five/six eyes with infectious
      virus confirmed by CC-IFA at enrollment, elimination of infectivity was achieved
      by day 4 or day 5. One patient was lost to followup. CONCLUSIONS: An ophthalmic
      suspension containing povidone-iodine 0.4% and dexamethasone 0.1% may be a useful
      agent in the treatment of acute RPS Adeno Detector-positive conjunctivitis. A
      further placebo-controlled study with a larger number of patients is warranted.

PMID- 19756416
TI  - Effect of glucosamine sulfate with or without omega-3 fatty acids in patients
      with osteoarthritis.
AB  - INTRODUCTION: A total of 177 patients with moderate-to-severe hip or knee
      osteoarthritis (OA) were tested over a period of 26 weeks in a two-center, two
      armed, randomized, double-blind, comparison study. The aim was to see if a
      combination of glucosamine sulfate (1500 mg/day) and the omega-3 polyunsaturated
      fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (group A),
      showed equivalence (noninferiority) or superiority as opposed to glucosamine
      sulfate alone (group B). METHODS: The primary therapy evaluation was performed
      using the Western Ontario and McMaster Universities Arthrosis index (WOMAC)
      score. At the end of the study, a reduction in the pain score of > or =20% was
      required (primary target criterion) and the quantitative difference in the WOMAC
      subscores pain, stiffness, and function were analyzed (secondary target
      criteria). RESULTS AND CONCLUSION: When a minimal pain reduction of > or =20% was
      chosen, there was no statistically significant difference in the number of
      responders between the two groups (92.2% group A, 94.3% group B). A higher
      responder criterion (> or =80% reduction in the WOMAC pain score) was chosen.
      Therefore, the frequency of responders showed a therapeutic and statistical
      superiority for the combination product of glucosamine sulfate and the omega-3
      polyunsaturated fatty acids in patients who complied with the study protocol
      (group A 44%, group B 32%; P=0.044). OA symptoms (morning stiffness, pain in hips
      and knees) were reduced at the end of the study: by 48.5%-55.6% in group A and by
      41.7%-55.3% in group B. The reduction was greater in group A than in group B.
      There was a tendency toward superiority shown in the secondary target criteria
      and concurrent variables. In the global safety evaluation, both products have
      been demonstrated to be very safe in long-term treatment over 26 weeks. To our
      knowledge, this is the first clinical trial in which glucosamine was given in
      combination with omega-3 fatty acids to patients with OA.

PMID- 19756417
TI  - Persistent Helicobacter canis bacteremia in a patient with gastric lymphoma.
AB  - A 78-year-old man with gastric diffuse large B cell lymphoma presented with
      persistent Helicobacter canis bacteremia while receiving chemotherapy. An
      examination of his medical history revealed a close exposure to dogs. The patient
      recovered after 4 weeks of antibiotic therapy. Immunocompromised persons who
      maintain close contacts with dogs maybe at risk for this infection.

PMID- 19756418
TI  - Tobramycin once- vs thrice-daily for elective intravenous antipseudomonal therapy
      in pediatric cystic fibrosis patients.
AB  - PURPOSE: We hypothesized that a single intravenous (iv) tobramycine infusion
      (treatment B) would have equivalent anti-infectious efficacy in chronic
      Pseudomonas aeruginosa (PA) infection in cystic fibrosis (CF) as the commonly
      performed treatment of three doses (treatment A) . Toxicity and practicability
      may even be improved in the single-dose regimen. METHODS: This was a randomized
      crossover study comparing outcome after 14 and 35 days. The primary end-point was
      a decrease in the leukocyte count, and the secondary end-points were clinical and
      lung function parameters, Pseudomonas quantification in sputum, and inflammation
      markers (immunoglobulin G, C-reactive protein) in serum. 30 patients (20 female,
      mean age 11.2 years, mean age range 1.7-18.1 years) received elective 14-day
      courses of treatments A or B, followed by the alternative treatment after a mean
      interval of 37 (+/- 21) weeks. RESULTS: With the exception of PA density, there
      were no significant differences between both treatment strategies after 14 days
      of treatment. After 35 days of treatment, there were no significant changes in
      the leukocyte count and inflammation markers. Both treatment strategies reduced
      the bacterial load in the airways, as reflected by a decreased PA density in
      sputum. Nephrotoxicity was equal in both groups, with a transient slight
      elevation of urinary N-acetyl-beta-glucosaminidase concentrations. Standard
      audiometry tests revealed no evidence of a hearing impairment in any patient
      following therapy. Mean body weight increased during the study period by 0.5 kg.
      Forced expiratory volume increased by approximately 5% of the predicted volume,
      forced vital capacity increased by 2% of predicted capacity, and forced mid
      expiratory flow rate increased by 7% (A) or 4% (B) of the predicted normal value,
      although these changes were not statistically significant. CONCLUSION: We
      conclude that tobramycin given in a daily single dose (with the advantage of
      being more practical in a home environment) has an efficacy equal to that of
      three daily doses in terms of elective antipseudomonal therapy in clinically
      stable patients with CF.

PMID- 19756419
TI  - Continuous vs thrice-daily ceftazidime for elective intravenous antipseudomonal
      therapy in cystic fibrosis.
AB  - BACKGROUND/AIM: We hypothesized that a continuous 24-h infusion of 100 mg/kg per
      day ceftazidime (treatment C) would result in equivalent or even superior anti
      infectious efficacy in chronic Pseudomonus aeruginosa (PA) infection in patients
      with cystic fibrosis (CF) in comparison to the usual application of 200 mg/kg per
      day ceftazidime in three doses (treatment T). METHODS: This was a randomized
      crossover study comparing outcome after 14 days and 35 days. Tobramycin
      administered once daily (10 mg/kg per day) was administered concomitantly in both
      groups. The primary end-point was a decrease in the leukocyte count, and the
      secondary endpoints were clinical and lung function parameters, Pseudomonas
      quantification in sputum, and inflammation markers (immunogloblulin [Ig] G, C
      reactive protein [CRP]) in serum. All patients received antibiotics electively as
      14-day courses on a regular basis, not for acute exacerbations. RESULTS: Fifty
      six patients (29 females, mean patient age 14.4 years, age range 5-37) initially
      received treatments C or T, followed by the alternative treatment after a mean
      interval of 37 (+/- 21) weeks. After 2 weeks of antibiotic treatment, the overall
      study group showed significant improvements compared to baseline for body weight,
      leukocyte counts, CRP, forced expiratory volume in 1 s (FEV(1)), FVC (forced
      vital capacity), and bacterial load in the airways, with no significant
      differences between treatment groups. Both regimens were well tolerated. Three
      weeks after cessation of antimicrobial therapy, leukocytes and PA density had
      returned to pre-treatment values. CONCLUSION: We conclude that continuous or
      thrice-daily dosing of intravenous ceftazidime, both combined with once-daily
      tobramycin, are equally effective application regimens for elective
      antipseudomonal therapy in clinically stable patients with CF.

PMID- 19756420
TI  - [Long-term investigation of the risk of malignant diseases following intravenous
      radium-224 treatment for ankylosing spondylitis].
AB  - BACKGROUND AND PURPOSE: In German-speaking countries, the intravenous treatment
      of ankylosing spondylitis (AS) with radium-224 ((224)Ra) was common between the
      late 1940s and 2005. In this long-term investigation, the risk of malignant
      diseases following intravenous (224)Ra treatment for AS was assessed. PATIENTS
      AND METHODS: In a prospective long-term study, 1,471 patients with AS who were
      treated with (224)Ra between 1948 and 1975 have been followed together with a
      control group of 1,324 AS patients treated neither with radioactive drugs nor
      with X-rays. Standardized questionnaires to evaluate the patients' health status
      were used. Observed numbers of malignant diseases were compared with those of the
      control group as well as with expected numbers for a normal population. RESULTS:
      After 26 years of follow-up, causes of death have been certified for 1,006
      patients of the exposure group (control group: 1,072 patients). Significantly
      increased rates of myeloid leukemia (12 cases observed vs. 2.9 expected; p <
      0.001), kidney cancer (18 vs. 9.1; p < 0.01), thyroid cancer (4 vs. 1.2; p =
      0.03) and borderline significantly increased rates of cancer of female genital
      organs (10 vs. 5.6; p = 0.06) were found in the exposure group in contrast to no
      significant increases of these diseases in the control group. Rates of pulmonary
      and gastrointestinal malignancies were not increased. Lymphatic leukemia
      (exposure group: 8 vs. 2.7; p < 0.01; control group: 7 vs. 3; p = 0.03) was
      significantly elevated due to a high rate of chronic lymphatic leukemia in both,
      the exposure as well as the control group. CONCLUSION: Treatment of AS with
      (224)Ra led to increased incidences of myeloid leukemia and malignancies of
      kidneys, thyroid and female genital organs. Although this kind of therapy is now
      abandoned, there is a need for close follow-up of patients who received it.

PMID- 19756421
TI  - Downstaging of pancreatic carcinoma after neoadjuvant chemoradiation.
AB  - BACKGROUND AND PURPOSE: Neoadjuvant chemoradiation could improve survival in
      patients with pancreatic cancer because of a higher rate of R0 resections, lower
      rate of nodal metastasis (ypN) and of local recurrence. This approach was tested
      in a cohort to estimate its effect on survival. PATIENTS AND METHODS: Three
      dimensional, conformal radiation to the primary tumor (55.8 Gy) and the
      lymphatics (50.4 Gy) was combined with chemotherapy. Resection was performed 6
      weeks after completion of chemoradiation. RESULTS: 38 of 120 patients with
      locally advanced cancer underwent tumor resection thereafter. Three patients (8%)
      had pathologic complete response. Median tumor-specific survival was 29 months
      and overall survival 25 months. Patients with clear margins (35/38; 89%) had a 3
      year disease-specific survival rate of 51% versus 0% with positive margins (p =
      0.008). Nodal disease rate decreased from 50% at pretherapeutic imaging to 32% at
      resection. Patients with ypN0 status (n = 26/38) had a 3-year tumor-specific
      survival rate of 50% compared to 31% in patients with ypN1 status. At
      multivariate analysis, resection status and nodal spread significantly predicted
      tumor-specific survival. Chemoradiation was generally well tolerated. CONCLUSION:
      The current results support randomized testing of neoadjuvant chemoradiation to
      prove survival prolongation. Compared to the literature this approach seems to
      reduce the number of positive nodes.

PMID- 19756422
TI  - Comparison of stereotactic radiosurgery and fractionated stereotactic
      radiotherapy of acoustic neurinomas according to 3-D tumor volume shrinkage and
      quality of life.
AB  - BACKGROUND AND PURPOSE: Stereotactic radiosurgery (SRS) and also fractionated
      stereotactic radiotherapy (SRT) offer high local control (LC) rates (> 90%). This
      study aimed to evaluate three-dimensional (3-D) tumor volume (TV) shrinkage and
      to assess quality of life (QoL) after SRS/SRT. PATIENTS AND METHODS: From 1999 to
      2005, 35/74 patients were treated with SRS, and 39/74 with SRT. Median age was 60
      years. Treatment was delivered by a linear accelerator. Median single dose was 13
      Gy (SRS) or 54 Gy (SRT). Patients were followed up > or = 12 months after
      SRS/SRT. LC and toxicity were evaluated by clinical examinations and magnetic
      resonance imaging. 3-D TV shrinkage was evaluated with the planning system. QoL
      was assessed using the questionnaire Short Form-36. RESULTS: Median follow-up was
      50/36 months (SRS/SRT). Actuarial 5-year freedom from progression/overall
      survival was 88.1%/100% (SRS), and 87.5%/87.2% (SRT). TV shrinkage was
      15.1%/40.7% (SRS/SRT; p = 0.01). Single dose (< 13 Gy) was the only determinant
      factor for TV shrinkage after SRS (p = 0.001). Age, gender, initial TV, and
      previous operations did not affect TV shrinkage. Acute or late toxicity (> or =
      grade 3) was never seen. Concerning QoL, no significant differences were observed
      after SRS/SRT. Previous operations and gender did not affect QoL (p > 0.05).
      Compared with the German normal population, patients had worse values for all
      domains except for mental health. CONCLUSION: TV shrinkage was significantly
      higher after SRT than after SRS. Main symptoms were not affected by SRS/SRT.
      Retrospectively, QoL was neither affected by SRS nor by SRT.

PMID- 19756423
TI  - Surface dose in the treatment of breast cancer with helical tomotherapy.
AB  - PURPOSE: Investigation of the effects of breathing motion- and misregistration
      induced errors on the superficial dose in the treatment of breast cancer using
      helical tomotherapy (HT). MATERIAL AND METHODS: Surface dose measurements were
      performed with thermoluminescence dosimetry (TLD). Two treatment plans with
      different planning target volume (PTV) definitions of the left breast were used:
      PTVskin had its ventral border exactly on skin level, while PTVair included also
      a 10-mm extension ventral to the PTVskin. With a thoracic static phantom,
      misregistration errors in an HT were simulated. A dynamic phantom was used to
      simulate a breathing patient during HT. Surface doses of breast cancer patients
      were measured both for an HT (179 points) and a conventional three-dimensional
      conformal treatment (70 points). RESULTS: In the static phantom misregistration
      setup, dose deviations of -31.9% for PTVskin to +35.4% for PTVair could be
      observed. The dynamic phantom measurements resulted in surface dose deviations
      from those in a static position between 0.8% and 3.8% without a significant
      difference for the PTV definitions. The measured surface doses on patients
      averaged (mean +/- standard deviation) 1.65 +/- 0.13 Gy for the HT and 1.42 +/-
      0.11 Gy for the three-dimensional conformal treatment. CONCLUSION: HT enables a
      homogeneous and reproducible surface dose with small dose deviations in the
      treatment of breast cancer. HT is a feasible method to treat breast cancer under
      free shallow breathing of the patient using a treatment plan with a ventral PTV
      border on the skin level.

PMID- 19756424
TI  - Concomitant radiochemotherapy of cervical cancer: is it justified to reduce the
      dosage of cisplatin?
AB  - PURPOSE: To review the experiences regarding the therapeutic response and side
      effects of concomitant radiochemotherapy of cervical cancer carried out with
      different cisplatin doses. PATIENTS AND METHODS: At the Municipal Center for
      Oncoradiology, Budapest, Hungary, 92 patients with cervical cancer were treated
      with concomitant radiochemotherapy in the period between July 2002 and March
      2007. The total dose of high-energy external radiation (megavoltage) treatment
      was 50.4 Gy with a fraction dose of 1.8 Gy on the small pelvis. Before
      irradiation, cisplatin 40 mg/m(2), 30 mg/m(2), or 20 mg/m(2) was administered
      once a week. RESULTS: In 17 cases, the cisplatin dose was 30 mg/m(2); during
      radiochemotherapy the number of cisplatin treatments was equal to or more than
      four in 14 patients (82%). After administering 40 mg/m(2) cisplatin to 64
      patients, chemotherapy in four or more treatments could only be applied in 37
      cases (58%). Eleven patients received cisplatin at the dose of 20 mg/m(2); in ten
      (91%) of them, the number of treatments was four or more. By comparing the side
      effects, it can be stated that hematologic side effects (mostly leukopenia) grade
      3 occurred in 12% of the patients receiving cisplatin 30 mg/m(2), and grade G3-4
      in 16% of the 40-mg/m(2) cisplatin group. For cisplatin 30 mg/m(2), 82% of
      hematologic side effects were in the G1 range. There was no significant
      difference between the 20- and 30-mg/m(2) regimens. As for the gastrointestinal
      toxicity, similar side effects grade 1 were detected, which occurred in 58% and
      38% of the patients receiving 30 mg/m(2) and 40 mg/m(2), respectively.
      CONCLUSION: On the basis of a detailed analysis, the correlation between the
      number of treatments, the therapeutic and the side effects could be verified. In
      the course of dose reduction, there was no significant difference when comparing
      the results of therapy, however, the quality of life was better if cisplatin 30
      mg/m(2) was administered instead of 40 mg/m(2). If cisplatin 20 mg/m(2) was
      given, the results were significantly worse. On the basis of the own results, it
      can be stated that the optimal weekly dose of cisplatin is 30 mg/m(2).

PMID- 19756425
TI  - Using cone-beam computed tomography to evaluate the impact of bladder filling
      status on target position in prostate radiotherapy.
AB  - PURPOSE: To assess bladder filling status and its impact on target position
      during daily intensity-modulated radiation therapy (IMRT) using cone-beam
      computed tomography (CBCT) in prostate cancer patients. PATIENTS AND METHODS: 23
      patients with prostate cancer undergoing image-guided IMRT (78 Gy in 39
      fractions) were included. On-board CBCT images were acquired daily and an
      endorectal balloon was placed daily. All patients were instructed to have a full
      bladder. The interfraction changes in bladder dimensions in left-right (LR),
      anterior-posterior (AP), and superior-inferior (SI) directions were measured from
      CBCT images. Distances from the uppermost part of prostate to pubic bone (PP) and
      from the uppermost part of prostate to treatment isocenter (PI) were measured to
      determine changes in target position. Standard deviation (SD) in all fractions of
      each patient was used to compare the variations between patients. Bladder
      dimension change ratio and Z-score were used to normalize data between patients.
      RESULTS: A total of 867 CBCT images were evaluated. The average LR, AP, and SI
      bladder dimensions were 7.8 +/- 1.5 cm, 6.7 +/- 1.4 cm, and 5.6 +/- 1.7 cm,
      respectively. The average LR, AP, and SI bladder dimension change ratios were
      0.88 +/- 0.17, 0.90 +/- 0.15, and 0.86 +/- 0.32, respectively. The SD was
      significantly greater in SI dimension than in LR (p < 0.001) and AP (p < 0.001)
      dimensions. The interfraction changes in the three bladder dimensions were
      significantly larger than those of target position, and did not correlate with
      target position changes. CONCLUSION: Though they were not negligible, changes in
      bladder filling status did not have a significant impact on target position.

PMID- 19756426
TI  - Effect of a prostaglandin--given rectally for prevention of radiation-induced
      acute proctitis--on late rectal toxicity. Results of a phase III randomized,
      placebo-controlled, double-blind study.
AB  - BACKGROUND AND PURPOSE: To assess the late effect of a prostaglandin, given
      rectally during irradiation, on late rectal toxicity. In the acute treatment
      setting no significant differences in reducing the incidence of acute proctitis
      symptoms in patients receiving misoprostol, however, significantly more rectal
      bleeding had been reported. PATIENTS AND METHODS: A total of 100 patients who had
      undergone radiotherapy for prostate cancer had been entered into this phase III
      randomized, placebo-controlled, double-blind study with misoprostol or placebo
      suppositories. The toxicity was evaluated yearly after cessation of irradiation
      by the RTOG/LENT-SOMA scale. RESULTS: The median follow-up was 50 months. 20
      patients suffered from grade 1, four patients from grade 2 as well, and three
      patients only from grade 2 toxicity. Frequency, bleeding and urgency were the
      most commonly reported symptoms. In keeping with other studies and clinical
      experience, the symptoms peaked within the first 2 years with a median for grade
      1 of 13 months and for grade 2 of 15 months. The presence of acute toxicity grade
      2 showed a correlation with the development of any late toxicity (p = 0.03). Any
      acute rectal bleeding was significant correlated with any late rectal bleeding (p
      = 0.017). CONCLUSION: Misoprostol given as once-daily suppository for prevention
      of acute radiation-induced proctitis does neither influence the incidence and
      severity of radiation-induced acute nor late rectal toxicity. Misoprostol has no
      negative impact on the incidence and severity of late rectal bleeding, in
      contrast to acute rectal bleeding. The routine clinical use of misoprostol
      suppositories cannot be recommended.

PMID- 19756427
TI  - Localized morphea--a rare but significant secondary complication following breast
      cancer radiotherapy. Case report and review of the literature on radiation
      reaction among patients with scleroderma/morphea.
AB  - PURPOSE AND APPROACH: To report a case of morphea (localized scleroderma) in a
      patient following breast cancer therapy and to summarize the current literature.
      RESULTS AND CONCLUSION: The occurrence of morphea is an unexpected late effect
      (approximately 1 year after the end of radiation therapy) which occurs frequently
      in the irradiated breast in women with breast-conserving therapy. The
      pathogenesis is unclear. The main differential diagnoses are recurrence of
      carcinoma and a radiogenic subcutaneous fibrosis (in most cases, the final
      diagnosis can only be made by means of a biopsy). Diagnosis and therapy must be
      performed in cooperation between dermatologist and radiooncologist.

PMID- 19756429
TI  - [PAUL procedure. A new biocompatible concept for the therapy of congenital
      abdominal wall defects].
AB  - Treatment of small congenital abdominal wall defects (e.g. omphalocele and
      gastroschisis) can be performed by direct closure. In large defects non
      resorbable artificial materials (e.g. Gore-Tex) are necessary to close the
      fascia. The aim of this study was to find out whether a new procedure, the PAUL
      pocedure, might be suitable for the treatment of large abdominal wall defects. A
      full thickness abdominal wall defect was created in young Wistar Rats. These
      defects were then closed by implantation of a 1x2 cm sized piece of PTFE (Dual
      Mesh), a polypropylene mesh (Prolene(R)) or by using the PAUL procedure. Over a
      period of 6 weeks no wound infections or hernias were monitored. In contrast to
      PTFE the PAUL procedure showed only minimal adhesion to the intestine and a high
      stability of the implanted material. A xenogenic extracellular matrix, such as
      that used in the PAUL procedure, may induce an immune response, which is
      comparable with a remodeling reaction rather than rejection. Based on these good
      results a large animal model study (Goettinger mini-piglets) was performed. No
      wound infections or hernias could be observed throughout the experiment. Control
      laparoscopy after 3, 6, 9, and 12 months showed only minimal adhesion to the
      intestine. Our results indicate that the PAUL procedure can be used easily and
      successfully for the therapy of congenital abdominal wall defects.

PMID- 19756430
TI  - [Surgical intensive care medicine. Current therapy concepts for septic diseases].
AB  - The clinical appearance of septic disorders is characterized by an enormous
      dynamic. The sepsis-induced dysbalance of the immune system necessitates
      immediate and aggressive therapeutic interventions to prevent further damage
      progression of the disease to septic shock and multiple organ failure. This
      includes supportive therapy to normalize and maintain organ and tissue perfusion
      as well as the identification of the infection focus. In cases where an
      infectious focus is identified, surgical source control frequently is a key
      element of the treatment strategy besides pharmacologic and supportive measures.
      The integrative approach of the management of septic patients requires rapid
      communication between the involved medical disciplines and the nursing personnel.
      Therefore, this article outlines current therapeutic concepts of septic diseases
      as well as central nursing aspects.

PMID- 19756431
TI  - [Neoadjuvant therapy in the upper gastro-intestinal tract. Gastric cancer from a
      surgical viewpoint].
AB  - The prognosis of locally advanced gastric cancer remains poor. It has been shown
      that multimodal treatment can improve the outcome in comparison to surgery alone.
      Two randomized studies that have been performed in Europe have shown that peri
      operative chemotherapy significantly improves the survival of patients with
      adenocarcinoma of the stomach and of the gastro-esophageal junction. These
      results have a profound effect on the treatment of patients presenting with stage
      II or stage III disease. For more than 10 years it has been accepted that
      responding patients have a significantly improved prognosis compared to non
      responding patients. Therefore, (early) response evaluation or response
      prediction is of utmost importance. After neoadjuvant chemotherapy patients
      should undergo a D-2 lymphadenectomy due to the high probability of lymph node
      metastasis. Neither mortality nor complication rate are increased after
      neoadjuvant chemotherapy for gastric cancer. Patients with locally advanced
      gastric cancer should always be referred to experienced high volume centers,
      where the findings are discussed in a multidisciplinary tumor board.

PMID- 19756432
TI  - [Hepatic trauma. Interventional and conservative therapy].
AB  - The non-operative management of hemodynamically stable patients with liver trauma
      has become the standard of care. Non-operative treatment has a success rate of
      >80%. In the majority of cases of hemodynamic instability or high grade liver
      injuries, however, a surgical approach is necessary. As for conservative
      treatment of liver trauma the surveillance of patients in the ICU is of utmost
      importance. Repeat CT scans are only necessary in patients with high grade
      injuries or in case of complications. Interventional procedures, such as the
      endoscopic retrograde cholangiopancreatography in cases of biliary complications
      or angiography for vascular complications, are increasingly being used in order
      to avoid surgery. The success rates of non-operative strategies have been
      improving continuously over the last decades.

PMID- 19756433
TI  - [Postoperative complications in trauma surgery].
AB  - In the literature it has been unanimously reported that here is a heavy burden on
      operative disciplines due to the occurrence of complications and the commonly
      resulting accusation of an error in treatment. Most of these accusations affect
      the discipline of surgery and in the main aspects trauma surgery is
      disproportionally represented. This substantial burden and high rate of
      accusations against trauma surgery arises from the high transparency as
      complications in trauma surgery are visualizable. Dealing with complications is
      therefore an elementary function of trauma surgeons. The analysis of
      postoperative complications shows clearly that in most cases they do not only
      result from the postoperative course. The causes of postoperative complications
      in many cases are more likely to have already begun in the pre-operative and peri
      operative phases. Pre-existing diseases and risk factors as well as operation
      planning and establishing indication status are in many cases the pre-operative
      and intra-operative origins of postoperative complications. In the present
      article the authors attempt to address the issues of new aspects of complications
      and therefore the quality management of trauma surgery, without making claim to
      completeness.

PMID- 19756434
TI  - [Solarium-induced pseudoporphyria and variegate porphyria as rare differential
      diagnoses of porphyria cutanea tarda].
AB  - Three patients presented with typical porphyria cutanea tarda-like vesicles,
      erosions and scars as well as increased fragility, primarily on the back of the
      hands. In two of the three, porphyrin workup was normal. Skin biopsy was
      compatible with porphyria cutanea tarda (PCT) or pseudoporphyria. The common
      aspect in the patients' history was the frequent use of solaria for many years,
      so that UV-induced pseudoporphyria was diagnosed. Treatment was strict abstention
      from UV radiation and regular dermatologic controls for signs of skin damage.
      Porphyrin analysis in the third patient showed normal excretion of total urine
      porphyrins and precursors; however, fecal porphyrins were elevated with
      dominating coproporphyrins in HPLC and the plasma fluorescence scan yielded a
      peak at 625 nm. Subsequent mutation analysis showed a mutation in the
      protoporphyrinogen oxidase gene, thereby confirming the diagnosis of variegate
      porphyria. Five months after the initial diagnosis the patient presented with the
      first acute attack. Further investigations revealed a metastasized carcinoma of
      the colon, which probably triggered the acute attack. Our cases show rare
      differential diagnoses in patients presenting with typical PCT-like skin lesions.
      The discrimination between porphyria cutanea tarda and its differential diagnoses
      is very important since it has an important impact not only on the treatment
      modality but also on the course and the prognosis of the disease.

PMID- 19756435
TI  - [Giant condyloma of the penis with malignant transformation associated with
      lichen sclerosus et atrophicus].
AB  - A 72-year old patient presented with a 6 months history of a rapidly growing
      tumor of the glans and foreskin. He had a long history of phimosis with lichen
      sclerosus et atrophicus-like lesions on the foreskin which had not been treated.
      The rest of the personal, family and sexual history was unremarkable. Treatment
      consists of circumcision and tumor excision. Histopathology confirmed a squamous
      cell carcinoma within a giant condyloma with a concomitant lichen sclerosus et
      atrophicus. CT- and ultrasound scans showed no metastases. Giant condylomas are a
      rare sexually transmitted disease usually caused by human papilloma virus
      subtypes 6, 11, but also by 16 and 18 among others. They are expansive,
      cauliflower-like destructive lesions that most frequently affect the anogenital
      region. In about 30 percent a giant condyloma progresses into a squamous cell
      carcinoma. Therapy of choice is the histopathologically controlled excision.
      Recurrences are often seen, so the patients should be monitored frequently after
      therapy.

PMID- 19756436
TI  - [Cutaneous side effects of hydroxyurea treatment for  polycythemia vera].
AB  - A 68-year-old women with polycythemia vera was treated with hydroxyurea for 8
      years and developed painful ulcers on her lower legs, multiple hypertrophic
      actinic keratoses and a squamous cell carcinoma. After discontinuing hydroxyurea
      therapy the leg ulcers resolved within 8 weeks. The hypertrophic actinic
      keratoses and squamous cell carcinoma were treated with cryotherapy and excision,
      respectively. Hydroxyurea induces a variety of cutaneous side effects such as
      painful leg ulcers and squamous cell carcinomas. Given the wide variety of
      adverse cutaneous side effects associated with long-term hydroxyurea therapy, the
      first step in management is to insure that physicians and patients are aware of
      the specific risks of this treatment. Patients under hydroxyurea therapy should
      be monitored closely by dermatologists to early detect and treat the cutaneous
      side effects.

PMID- 19756437
TI  - [Accumulation of tattoo pigment in sentinel lymph nodes].
AB  - A 22-year-old woman presented with a superficial spreading melanoma on her right
      thigh (tumor thickness 1.0 mm, Clark-Level III). She also had decorative tattoos
      on her right ankle, right groin and coccyx. The staging results gave no
      indication for metastases. Intra-operatively, we observed a black pigmented lymph
      node highly suspicious for metastatic disease, but histological examination
      excluded metastatic spread and detected the accumulation of black pigment within
      the lymph node. Clinical differentiation between tattoo pigments and metastatic
      disease within lymph nodes is not possible. Histological confirmation of an
      enlarged pigmented lymph node is therefore essential before radical surgery is
      performed. Hence, accumulation of tattoo pigment within enlarged and pigmented
      lymph nodes needs to be included into the differential diagnosis and the
      documentation of decorative tattoos is important during skin cancer screening as
      well as during the follow-up of melanoma patients.

PMID- 19756438
TI  - [Transition in internal medicine. Special care in the passage from adolescence to
      adult age].

PMID- 19756439
TI  - [60-year old woman with round lesion of the right upper lobe of the lung after
      heart transplantation].
AB  - We report on a woman presenting with fever and novel round lesion in the lung
      four months after heart transplantation. Microbiologic assessment of bronchial
      lavage and operative specimen revealed pulmonary nocardiosis. Furthermore,
      cerebral involvement has been observed. Antibiotic treatment according to the
      microbiological sensitivity test for eleven months resulted in complete remission
      of pulmonary and cerebral nocardiosis. Immunosuppressive treatment increases the
      risk for opportunistic infections early after transplantation as well as
      malignancies during the late course.

PMID- 19756440
TI  - [Severe anemia and chronic alcohol abuse lacking signs of gastrointestinal
      bleeding in a 40-year-old].
AB  - We report about a 40 year old patient presenting a severe anemia caused by a
      folate deficiency combined with chronic alcohol abuse and probable liver
      cirrhosis. Besides pathophysiology and etiology of folate deficiency the
      correlation of malnutrition and liver cirrhosis (in particular caused by alcohol
      abuse) is discussed. As a conclusion for clinical practice the necessity of an
      extensive investigation for causes of an existing anemia, even in cases, which
      very much seem to be caused by an acute bleeding event, shall be demonstrated.
      Furthermore this report shows the importance of a consistent nutrition counseling
      of patients with liver cirrhosis.

PMID- 19756441
TI  - [Hepatomegaly und elevated transaminases in a 24-year-old with type I diabetes
      mellitus].
AB  - Poorly controlled type I diabetes mellitus can lead to excessive hepatic glycogen
      storage, which is accompanied by elevated transaminases and hepatomegaly. Few
      cases have been reported and described as glycogenic hepatopathy. There is
      characteristically no progression to fibrosis and cirrhosis and the symptoms are
      reversible with improved glycemic control.

PMID- 19756442
TI  - [Congenital heart disease.   Transition from adolescence to adulthood].
AB  - There is a increasing clinical and scientific interest in adults with congenital
      heart disease. Germany is among, if not the first country worldwide, with a
      structured care of adults with congenital heart disease. Due to the advances in
      cardiology and in heart surgery, the primarily high mortality rate of relevant
      congenital heart disease has declined from 80% to less than 20% during the recent
      decades. Currently, in Europe the estimated number of adults with congenital
      heart disease is between 1.2 and 2.7 Mio., and the number in Germany exceeds
      180,000. Almost all congenital heart defects, either native or interventionally
      or surgically treated, need regular control, since even after successful primary
      treatment significant residua or sequels have to be expected. Optimal care of
      these patients begins in the childhood and must be continued down to the high
      adulthood. The complexity of congenital heart defects makes a multidisciplinary
      approach necessary. A specialized, interdisciplinary cooperation between
      cardiologists, pediatric cardiologists, cardiac surgeons and other specialists is
      mandatory.

PMID- 19756443
TI  - [Reduced bone density and bone pain :osteomalacia with hypophospatemia and
      hypophosphaturia].
AB  - Two patients aged 24 and 64 years presented at our hospital with similar symptoms
      including bone pain and muscle weakness. Basic laboratory tests and urinary
      diagnostics, bone densitometry and bone histology revealed severe osteomalacia
      with renal phosphate wasting. After the exclusion of other causes an extensive
      tumor search was performed due to suspected tumor-induced osteomalacia. In one
      patient a mesenchymal tumor was found in the thigh and completely resected. After
      surgery the patient showed a rapid recovery from osteomalacia. Because the search
      was unsuccessful in the other patient phosphorus supplementation in combination
      with calcitriol was started. Despite continuing renal phosphate wasting a
      significant increase in bone mineral density was observed.

PMID- 19756447
TI  - Therapeutic potential of olfactory ensheathing cells in neurodegenerative
      diseases.
AB  - The regenerative capacity of the olfactory system has generated interest in
      potential clinical application of cells from the olfactory epithelium in the
      treatment of neurodegenerative diseases. Experimental evidence from animal models
      and clinical studies suggest that transplantation of olfactory ensheathing cells
      (OEC), specialized glia in the olfactory system, may be therapeutically useful in
      neurodegenerative diseases such as spinal cord injury and stroke. This review
      article describes the different experimental approaches in OEC transplantation.
      We also discuss the possible effects of OEC implantation on the underlying
      pathophysiology in neurological disease, including neuroplasticity. Our recent
      study of this particular population of cells has disclosed some of the molecular
      basis of the regenerative mechanism of OECs. In summary OECs produce several
      neurotrophic factors such as stromal cell-derived factor 1alpha and brain-derived
      neurotrophic factor and enhance axonal regeneration to promote neuroplasticity in
      neurodegenerative diseases.

PMID- 19756448
TI  - A novel mechanism for inflammation-associated  carcinogenesis; an important role
      of activation-induced  cytidine deaminase (AID) in mutation induction.
AB  - Inflammation is a risk for cancer development; however, its mechanism is unknown.
      Recent studies have revealed that activation-induced cytidine deaminase (AID),
      which plays essential roles in both class-switch recombination and somatic
      hypermutation of immunoglobulin gene in B lymphocytes, is aberrantly expressed in
      non-lymphoid cells not only by H.pylori and HCV infection but also by various
      proinflammatory cytokines, leading to the generation of gene mutations. These
      findings not only suggested a new mechanism of inflammation-associated
      carcinogenesis but has also opened up a new field of tumor biology.

PMID- 19756449
TI  - Sgk1 activates MDM2-dependent p53 degradation and affects cell proliferation,
      survival, and differentiation.
AB  - Serum and glucocorticoid regulated kinase 1 (Sgk1) is a serine-threonine kinase
      that is activated by serum, steroids, insulin, vasopressin, and interleukin 2 at
      the transcriptional and post-translational levels. Sgk1 is also important in
      transduction of growth factors and steroid-dependent survival signals and may
      have a role in the development of resistance to cancer chemotherapy. In the
      present paper, we demonstrate that Sgk1 activates MDM2-dependent p53
      ubiquitylation. The results were obtained in RKO cells and other cell lines by
      Sgk1-specific RNA silencing and were corroborated in an original mouse model as
      well as in transiently and in stably transfected HeLa cells expressing wild-type
      or dominant negative Sgk1 mutant. Sgk1 contributes to cell survival, cell-cycle
      progression, and epithelial de-differentiation. We also show that the effects of
      Sgk1 on the clonogenic potential of different cancer cells depend on the
      expression of wild-type p53. Since transcription of Sgk1 is activated by p53, we
      propose a finely tuned feedback model where Sgk1 down-regulates the expression of
      p53 by enhancing its mono- and polyubiquitylation.

PMID- 19756450
TI  - Modulation of bone marrow stromal cell functions in infectious diseases by toll
      like receptor ligands.
AB  - Bone marrow-derived stromal cells (BMSCs, or as they are frequently referred to
      as mesenchymal stem cells) have been long known to support hematopoiesis and to
      regenerate bone, cartilage, and adipose tissue. In the last decade, however, a
      vast amount of data surfaced in the literature to suggest new roles for these
      cells including tissue regeneration and immunomodulation. A great number of
      review articles appeared that summarize these new data and focus on different
      aspects of the physiology of these cells. In this present short review, we will
      try to summarize the available data based on both mouse and human cells
      describing how the function of BMSCs might be affected by an infectious
      environment. These data strongly support the idea that different toll-like
      receptor ligands can lead to substantial changes in the function of BMSCs that
      affect their proliferation, apoptosis, migration, and their production and
      release of immunomodulatory factors.

PMID- 19756451
TI  - [Standardised primary care of multiple trauma patients. Prehospital Trauma Life
      Support und Advanced Trauma Life Support].
AB  - INTRODUCTION: Standardised management improves treatment results in seriously
      injured patients. For conditions like stroke or acute coronary syndrome (ACS)
      there are set treatment pathways which have been established for prehospital and
      primary hospital care. The treatment of critical trauma patients, however,
      follows varying procedures in both the prehospital and primary hospital phases.
      From an analysis of the trauma register of the German Society for Trauma Surgery
      (DGU), we know that a seriously injured patient remains on the road for 70 min on
      average before transferral to hospital. This requires improvement. With the 2003
      introduction of the ATLS programme in Germany, the initial clinical phase could
      be improved upon simply by means of standardised training. PHTLS und ATLS
      complement one another. RESULTS: PHTLS und ATLS represent training concepts which
      teach standardised, priority-based prehospital and hospital trauma management.
      The aim is to make an initial rapid and accurate assessment of the patient's
      condition, thereby identifying the"critical" patient. The concepts also make
      priority-based treatment possible and facilitate decision-making as to whether
      patients can receive further on-the-spot treatment or whether immediate transport
      is necessary. The procedure is identical in the shock room. The primary
      consideration is to prevent secondary damage, not to lose track of time and to
      ensure consistent quality of care. The courses teach systematic knowledge,
      techniques, skills and conduct in diagnosis and therapy. The courses are oriented
      to all medical specialities associated with trauma care. With the support of the
      German Society for Trauma Surgery (DGU) and the German Society for Anesthesiology
      and Intensive Medicine (DGAI), the German Professional Organisation of Rescue
      Services (DBRD) has adopted the PHTLS course system on licence from the National
      Association of Emergency Medical Technicians (NAEMT) and the American College of
      Surgeons (ACS) and has been offering it in Germany since late 2007. ATLS was
      established by the DGU in 2003 and represents successful and similarly structured
      shock-room management. CONCLUSION: PHTLS und ATLS are established and
      standardised concepts, which are constantly reviewed and updated according to the
      latest medical knowledge. They provide the opportunity to standardise prehospital
      and primary clinical trauma management for all specialties and hospitals, while
      incorporating own knowledge.

PMID- 19756452
TI  - [Surgical management of life-threatening injuries].
AB  - Life-threatening situations after multiple trauma which then require interruption
      of the diagnostic algorithm and immediate surgical treatment after admission are
      a challenge for the multidisciplinary trauma team. Emergency surgery after trauma
      may be necessary for the abdomen, the pelvis, the chest as well as the head.
      Therefore, several disciplines may be involved. Damage control surgery is the
      leading surgical strategy in emergency surgery in unstable trauma patients. The
      main aspects of damage control surgery are outlined in this article. The goal of
      damage control surgery is to gain control of bleeding as soon as possible without
      additional surgical trauma. Packing plays a central role in damage control
      surgery of the abdomen and the pelvis. Surgical decision-making occurs under
      unfavorable circumstances and extreme time pressure. However, surgical
      interventions in the shock room rarely occur in the German health system.
      Therefore, indications and decision-making processes of these challenging
      situations have to be practiced with standardized algorithms. The "Definitive
      Surgical Trauma Care" (DSTC)- courses may contribute to a straightforward
      performance in an emergency operation.

PMID- 19756453
TI  - [Medial hip neck fracture: influence of pre-operative delay on the quality of
      outcome. Results of data from the external in-hospital quality assurance within
      the framework of secondary data analysis].
AB  - PROBLEM: According to international and national studies and clinical guidelines,
      patients with medial hip neck fracture should receive surgery as soon as
      medically reasonable after hospitalization, preferably within 48 h. Analysis of
      the German quality registry data of 2006 showed, however, that in 13 out of the
      16 federal states less than 85% of patients were operated on within 48. Delayed
      surgery was found especially during the weekend. OBJECTIVE: The objective of the
      study was to examine whether German data confirm that a short preoperative
      waiting time after hip fracture improves the outcome. The study was commissioned
      by the Federal Joint Committee (G-BA) and was jointly performed by the German
      Society for Accident Surgery (DGU) and the National Institute for Quality in
      Healthcare (BQS). DATA AND METHODS: The analysis is based on the data of the
      nationwide quality registry of the years 2004-2006. Out of a total of 129,075
      patients with a medial hip neck fracture 22,171 received operative treatment
      later than 48 h after hospital admission. Comparable study groups were
      constructed with the help of a propensity score (1-to-1 matching). Study and
      control groups only differed in terms of delay of surgery. The comparison
      concerning the outcomes was made with the Fisher exact test (bilateral). RESULTS:
      In the group of patients with a delay of surgery longer than 48 h significantly
      higher rates of surgical complications (OR 1.10), general complications (OR 1.09)
      and pressure ulcers (1.27) were observed (all p<0.001). The in-hospital mortality
      showed no significant difference (OR 0.96, p=0.302). CONCLUSIONS: Patients with
      medial hip neck fracture should receive operative treatment without delay, if no
      medical contra-indications for immediate surgery. In particular appropriate
      organizational measures should be taken to ensure an early surgical treatment
      even during weekends.

PMID- 19756454
TI  - [Distribution planning of injured persons in mass disasters or catastrophes.
      Structuring of hospital capacities exemplified by the catastrophe network of the
      German Society for Trauma Surgery (DGU)].
AB  - Relevant changes have occurred in disaster management in Germany due to legal
      alterations and the introduction of the diagnosis-related groups (DRG) system.
      This has resulted in a reduction in bed capacities and an increase in bed
      utilization. In addition to the preclinical deployment strategy the provisional
      aspects of disaster medicine with the problem of the emergency service/hospital
      interface will be described. A suggestion for a solution for optimization of
      patient allocation in mass disasters or catastrophes will be demonstrated with
      the catastrophe network of the German Society for Trauma Surgery (DGU).

PMID- 19756455
TI  - [The Trauma Network of the German Society for Trauma 2009].
AB  - In 2009, 3 years after the foundation of the Trauma Network of the German Society
      for Trauma (TraumaNetzwerkD DGU), the majority of German hospitals participating
      in the treatment of seriously injured patients is registered in regional trauma
      networks (TNW). Currently there are 41 trauma networks with more than 660
      hospitals in existence, 18 more are registered but are still in the planning
      phase. Each Federal State has an average of 39 trauma centres of different levels
      taking part in the treatment of seriously injured patients and every trauma
      network has an average catchment area of 8708 km(2). The most favourable
      geographical infrastructure conditions exist in Nordrhein-Westfalen, the least
      favourable in Sachsen-Anhalt and Mecklenburg-Vorpommern. A total of 95 hospitals
      have already fulfilled the first audit of the structural, personnel and
      qualitative requirements by the certification bodies. Examination of the check
      lists of 26 hospitals showed shortcomings in the clinical structure so that these
      hospitals must be rechecked after correction of the shortcomings. A total of 59
      hospitals throughout Germany were successfully audited and only one failed to
      fulfil the requirements. Because of the varying sizes of the trauma networks
      there are differences in the areas covered by each trauma network and trauma
      centre. Concerning the process of certification and auditing (together with the
      company DIOcert) it could be seen that by careful examination of the check lists
      of each hospital unforeseen problems during the audit could be avoided. The
      following article will present the current state of development of the Trauma
      Network of the German Society for Trauma and describe the certification and
      auditing process.

PMID- 19756456
TI  - [Damage Control Orthopedics. What is the current situation?].
AB  - Damage Control Orthopedics is a strategy for treatment of fractures in severely
      injured patients. The aim is to reduce secondary damage and thereby improve the
      patient's outcome. The relevant fractures are primarily stabilized with external
      fixators instead of a primary definitive osteosynthesis. The less traumatic and
      shorter surgical procedure is thought to reduce the additional trauma load and
      should thereby minimize the "second hit" situation. After stabilization of the
      patient on the intensive care unit secondary definitive ostesynthesis can then be
      performed after 4-14 days.The available animal studies, retrospective clinical
      studies and prospective cohort studies seem to support the concept of damage
      control. The only available randomized study shows an advantage of this strategy
      in a subgroup of borderline patients. A meta-analysis could not find convincing
      evidence that definitively proves the advantage of this concept. A new multi
      center randomized study has been started to evaluate the concept of damage
      control in a defined group of critically injured patients with femoral shaft
      fractures.

PMID- 19756457
TI  - [Transpedicular osteotomy with dorsal wedge osteotomy: treatment of post
      traumatic or postinfection kyphotic malalignment of the thoraco-lumbar spine].
AB  - BACKGROUND: The purpose of the study was to evaluate the clinical and
      radiological follow-up of patients suffering from fixed post-traumatic and
      postinflammatory kyphotic deformities of the thoracic and lumbar spine and
      treated by posterior transpedicular wedge resection osteotomy of the spine.
      METHODS: A total of 28 patients received a posterior transpedicular wedge
      resection osteotomy. A prospective follow-up was performed preoperatively,
      postoperatively and after 3, 6 and 12 months. The kyphotic angle of the fractured
      segment was evaluated as well as the clinical parameters the self-reported visual
      analog scale (VAS) and the Oswestry score. RESULTS: The median pain scores (VAS)
      and the Oswestry disability scores (p<0.05) decreased significantly from
      pretreatment to post-treatment. Postoperatively a significant correction of the
      kyphotic angle could be achieved with a mean of 28 degrees (range 14-44 degrees
      ). In the follow-up after 1 year there was a 7 degrees increase in kyphosis.
      CONCLUSIONS: Transpedicular wedge resection osteotomy of the thoracic and lumbar
      spine offers a safe surgical technique for the treatment of fixed
      postinflammatory kyphotic deformities.

PMID- 19756460
TI  - Fat and fed: frequent use of summer torpor in a subtropical bat.
AB  - A widely held view is that torpor is avoided by mammals whenever possible because
      of potential costs associated with reduced body temperatures and slowed metabolic
      processes. We examined this hypothesis by quantifying use of torpor in relation
      to body condition of free-ranging northern long-eared bats (Nyctophilus bifax,
      approximately 10 g), a species known to hibernate, from a subtropical region
      during the austral summer when insects were abundant. Temperature-telemetry
      revealed that bats used torpor on 85% of observation days and on 38% of all
      nights. Torpor bouts ranged from 0.7 to 21.2 h, but the relationship between
      duration of torpor bouts and ambient temperature was not significant. However,
      skin temperature of torpid bats was positively correlated with ambient
      temperature. Against predictions, individuals with a high body condition index
      (i.e., good fat/energy reserves) expressed longer and deeper torpor bouts and
      also employed torpor more often during the activity phase at night than those
      with low body condition index. We provide the first evidence that use of torpor
      in a free-ranging subtropical mammal is positively related with high body
      condition index. This suggests that employment of torpor is maximised and
      foraging minimised not because of food shortages or low energy stores but likely
      to avoid predation when bats are not required to feed.

PMID- 19756458
TI  - [Tissue engineering of bone tissue. Principles and clinical applications].
AB  - Complex fractures are still a major clinical challenge. The treatment options of
      large bony defects either with autografts or allografts are limited in terms of
      material availability and tissue in-growth. Tissue engineering might offer a
      solution to this problem. In an interdisciplinary approach artificial bony tissue
      can be generated which mimics normal bone in terms of function and morphology. So
      far tissue engineering of bone is mainly confined to laboratory investigations
      whereas clinical applications are still in the beginning. This manuscript
      presents the most important scaffolds as well as growth factors and cell systems.
      Furthermore, it focuses on clinical studies for the treatment of large bony
      defects using tissue engineered cell-matrix constructs.

PMID- 19756461
TI  - 'Special agents' trigger social waves in giant honeybees (Apis dorsata).
AB  - Giant honeybees (Apis dorsata) nest in the open and have therefore evolved a
      variety of defence strategies. Against predatory wasps, they produce highly
      coordinated Mexican wavelike cascades termed 'shimmering', whereby hundreds of
      bees flip their abdomens upwards. Although it is well known that shimmering
      commences at distinct spots on the nest surface, it is still unclear how
      shimmering is generated. In this study, colonies were exposed to living tethered
      wasps that were moved in front of the experimental nest. Temporal and spatial
      patterns of shimmering were investigated in and after the presence of the wasp.
      The numbers and locations of bees that participated in the shimmering were
      assessed, and those bees that triggered the waves were identified. The findings
      reveal that the position of identified trigger cohorts did not reflect the
      experimental path of the tethered wasp. Instead, the trigger centres were
      primarily arranged in the close periphery of the mouth zone of the nest, around
      those parts where the main locomotory activity occurs. This favours the 'special
      agents' hypothesis that suggest that groups of specialized bees initiate the
      shimmering.

PMID- 19756462
TI  - Charles Darwin's Origin of Species, directional selection, and the evolutionary
      sciences today.
AB  - The book On the Origin of Species, published in November 1859, is an "abstract"
      without references, compiled by Charles Darwin from a much longer manuscript
      entitled "Natural Selection." Here, I summarize the five theories that can be
      extracted from Darwin's monograph, explain the true meaning of the phrase
      "struggle for life" (i.e., competition and cooperation), and outline Darwin's
      original concept of natural selection in populations of animals and plants. Since
      neither Darwin nor Alfred R. Wallace distinguished between stabilizing and
      directional natural selection, the popular argument that "selection only
      eliminates but is not creative" is still alive today. However, I document that
      August Weismann (Die Bedeutung der sexuellen Fortpflanzung fur die Selektions
      Theorie. Gustav Fischer-Verlag, Jena, 1886) and Ivan Schmalhausen (Factors of
      evolution. The theory of stabilizing selection. The Blackiston Company,
      Philadelphia, 1949) provided precise definitions for directional (dynamic)
      selection in nature and illustrate this "Weismann-Schmalhausen principle" with
      respect to the evolutionary development of novel phenotypes. Then, the modern
      (synthetic) theory of biological evolution that is based on the work of
      Theodosius Dobzhansky (Genetics and the origin of species. Columbia University
      Press, New York, 1937) and others, and the expanded version of this system of
      theories, are outlined. Finally, I document that symbiogenesis (i.e., primary
      endosymbiosis, a process that gave rise to the first eukaryotic cells), ongoing
      directional natural selection, and the dynamic Earth (plate tectonics, i.e.,
      geological events that both created and destroyed terrestrial and aquatic
      habitats) were the key processes responsible for the documented macroevolutionary
      patterns in all five kingdoms of life. Since the evolutionary development of the
      earliest archaic bacteria more than 3,500 mya, the biosphere of our dynamic
      planet has been dominated by prokaryotic microbes. Eubacteria, Archaea, and
      Cyanobacteria are, together with eukaryotic microorganisms (marine phytoplankton,
      etc.), the hidden "winners" in the Darwinian struggle for existence in nature.

PMID- 19756463
TI  - Seeing it coming: infants' brain responses to looming danger.
AB  - A fundamental property of most animals is the ability to see whether an object is
      approaching on a direct collision course and, if so, when it will collide. Using
      high-density electroencephalography in 5- to 11-month-old infants and a looming
      stimulus approaching under three different accelerations, we investigated how the
      young human nervous system extracts and processes information for impending
      collision. Here, we show that infants' looming related brain activity is
      characterised by theta oscillations. Source analyses reveal clear localised
      activity in the visual cortex. Analysing the temporal dynamics of the source
      waveform, we provide evidence that the temporal structure of different looming
      stimuli is sustained during processing in the more mature infant brain, providing
      infants with increasingly veridical time-to-collision information about looming
      danger as they grow older and become more mobile.

PMID- 19756464
TI  - [Color duplex sonography of extracranial brain-supplying arteries].
AB  - Ultrasound examination of extracranial blood-supplying arteries allows the
      simultaneous acquisition of morphologic and hemodynamic information with high
      spatial and temporal resolution. For detection and quantification of stenoses in
      the carotid and vertebral arteries, an intrastenotic peak systolic velocity of
      more than 120 cm/s is the threshold value for a diameter reduction of >50%. In
      addition there are further direct and indirect stenosis parameters (intrastenotic
      and poststenotic circulation disturbance, increased pulsatility in the
      prestenotic common carotid artery, intracranial or extracranial collateral
      pathways) which together with diameter and area reduction in the B-scan, lead to
      a high reliability of color duplex sonography for stenoses of the internal
      carotid artery (ICA). Sonographic and patho-anatomic comparative studies have
      shown a high agreement (r >0.9) by using a battery of several ultrasound
      criteria. Following stenting of the ICA the blood flow velocity in the stent is
      generally increased so that a > or =70% in-stent restenosis is present in case of
      a peak systolic velocity of 300-450 cm/s. For the description of arteriosclerotic
      plaques in the B-scan, ultrasound terminology but not histological terms should
      be used to describe the internal, surface and motion structure of plaques as well
      as the sonic shadow formation.

PMID- 19756465
TI  - [Head injuries in children].
AB  - Trauma is the reason for 40-60% of emergency callouts concerning children.
      Approximately half of the children have head injuries. As for adults early
      recognition of findings indicating an intervention are decisive for the
      prognosis. In children head injury can be divided into three categories: birth
      trauma, accidental and non-accidental trauma. This article concentrates on
      accidental trauma with respect to characteristics of causes, epidemiology,
      mechanisms of accidents and illustrated morphological findings.

PMID- 19756466
TI  - [Chronic PDE-5 inhibition in patients with erectile dysfunction: new treatment
      approach using once daily Tadalafil].
AB  - Erectile dysfunction (ED) is often associated with increased cardiovascular risk.
      There is increasing evidence suggesting that dysfunction of the vascular
      endothelium with reduced bioavailability of nitric oxide (NO) may be the
      pathogenetic link between ED and cardiovascular disease. The crucial importance
      of the NO-guanylatecyclase-cGMP-phosphodiesterase pathway for penile erection is
      mirrored by the efficacy of phosphodiesterase-5 (PDE5) inhibitors in the
      treatment of ED. In contrast to other currently available PDE5 inhibitors with a
      half-life time of about 4 h Tadalafil has a half-life time of about 17.5 h
      resulting in erectile responsiveness for up to 36 h after 1 single dose. Most
      clinical experience has been reported with on-demand use of PDE-5 inhibitors, but
      meanwhile several studies were able to demonstrate that Tadalafil given daily in
      low (2.5 and 5 mg) doses is both highly effective and well-tolerated. In three
      randomized, double-blind, placebo-controlled multi-center trials, various
      validated measures of erectile function indicated that once daily Tadalafil at
      doses of 2.5, 5, and 10 mg was significantly superior to placebo.In another mono
      center trial, once daily Tadalafil has shown significant efficacy even after
      failure of on-demand treatment. In a controlled cross-over study of on-demand
      versus daily Tadalafil treatment, 72% of the patients preferred once daily
      administration, mainly because of superior and longer efficacy allowing a more
      spontaneous sexual life. Interestingly in a pilot study of on-demand versus
      chronic administration of Tadalafil for 4 weeks, only regular dosing improved
      several markers of endothelial function.

PMID- 19756468
TI  - [Diagnostic and differential diagnosis of benign prostate syndrome (BPS):
      guidelines of the German Urologists].

PMID- 19756467
TI  - [Therapy of benign prostate syndrome (BPS): guidelines of the German Urologists
      (DGU)].

PMID- 19756469
TI  - Genetic diversity and population structure of common bean (Phaseolus vulgaris L.)
      landraces from the East African highlands.
AB  - The East African highlands are a region of important common bean production and
      high varietal diversity for the crop. The objective of this study was to uncover
      the diversity and population structure of 192 landraces from Ethiopia and Kenya
      together with four genepool control genotypes using morphological phenotyping and
      microsatellite marker genotyping. The germplasm represented different common bean
      production ecologies and seed types common in these countries. The landraces
      showed considerable diversity that corresponded well to the two recognized
      genepools (Andean and Mesoamerican) with little introgression between these
      groups. Mesoamerican genotypes were predominant in Ethiopia while Andean
      genotypes were predominant in Kenya. Within each country, landraces from
      different collection sites were clustered together indicating potential gene flow
      between regions within Kenya or within Ethiopia. Across countries, landraces from
      the same country of origin tended to cluster together indicating distinct
      germplasm at the national level and limited gene flow between the two countries
      highlighting divided social networks within the regions and a weak trans-national
      bean seed exchange especially for landrace varieties. One exception to this may
      be the case of small red-seeded beans where informal cross-border grain trade
      occurs. We also observed that genetic divergence was slightly higher for the
      Ethiopian landraces compared to Kenyan landraces and that Mesoamerican genotypes
      were more diverse than the Andean genotypes. Common beans in eastern Africa are
      often cultivated in marginal, risk-prone farming systems and the observed
      landrace diversity should provide valuable alleles for adaptation to stressful
      environments in future breeding programs in the region.

PMID- 19756470
TI  - Analysis of diversity and linkage disequilibrium along chromosome 3B of bread
      wheat (Triticum aestivum L.).
AB  - A highly polymorphic core collection of bread wheat and a more narrow-based
      breeding material, gathered from pedigrees of seven modern cultivars, was
      analysed in order to compare genetic diversity indices and linkage disequilibrium
      (LD) patterns along the chromosome 3B with microsatellite (SSR) and Diversity
      Arrays Technology markers. Five ancestral gene pools could be identified within
      the core collection, indicating a strong geographical structure (Northwest
      Europe, Southeast Europe, CIMMYT-ICARDA group, Asia, Nepal). The breeding
      material showed a temporal structure, corresponding to different periods of
      breeding programmes [old varieties (from old landraces to 1919), semi-modern
      varieties (1920-1959), modern varieties (1960-2006)]. Basic statistics showed a
      higher genetic diversity in the core collection than in the breeding material,
      indicating a stronger selection pressure in this latter material. More generally,
      the chromosome 3B had a lower diversity than the whole B-genome. LD was weak in
      all studied materials. Amongst geographical groups, the CIMMYT-ICARDA pool
      presented the longest ranged LD in contrast to Asian accessions. In the breeding
      material, LD increased from old cultivars to modern varieties. Genitors of seven
      modern cultivars were found to be different; most marker pairs in significant LD
      were observed amongst genitors of Alexandre and Koreli varieties, indicating an
      important inbreeding effect. At low genetic distances (0-5 cM), the breeding
      material had higher LD than the core collection, but globally the two materials
      had similar values in all classes. Marker pairs in significant LD are generally
      observed around the centromere in both arms and at distal position on the short
      arm of the chromosome 3B.

PMID- 19756471
TI  - Map-based cloning of the ERECT PANICLE 3 gene in rice.
AB  - Panicle architecture in rice can have a strong influence on yield. Using N-methyl
      N-nitrosourea mutagenesis, we isolated an erect panicle mutant, Hep, from
      Hwasunchalbyeo, a glutinous japonica rice cultivar. Genetic analysis revealed
      that the erect panicle phenotype was controlled by a single recessive mutation
      designated erect panicle 3 (ep3). Genetic mapping revealed that the ep3 mutation
      was located on the short arm of chromosome 2 in a 0.1 cM region delimited by the
      STS markers STS5803-5 and STS5803-7. The ep3 locus corresponded to 46.8 kb region
      and contained six candidate genes. Comparison of the DNA sequences of the
      candidate genes from wild-type and erect panicle plants revealed a single base
      pair change in the second exon of LOC_Os02g15950, which is predicted to result in
      a nonsense mutation. LOC_Os02g15950 encodes a putative F-box protein containing
      515 amino acids and is expressed throughout the plant during all growth stages. A
      line carrying a T-DNA insertion in LOC_ Os02g15950 was obtained and shown to have
      the same phenotype as the ep3 mutant, thus confirming the identification of
      LOC_Os02g15950 as the ERECT PANICLE 3 (EP3) gene. The ep3 mutation causes a
      significant increase in the number of small vascular bundles as well as the
      thickness of parenchyma in the peduncle, which results in the erect panicle
      phenotype.

PMID- 19756472
TI  - Mapping of QTL for resistance to the Mediterranean corn borer attack using the
      intermated B73 x Mo17 (IBM) population of maize.
AB  - The Mediterranean corn borer or pink stem borer (MCB, Sesamia nonagrioides
      Lefebvre) causes important yield losses as a consequence of stalk tunneling and
      direct kernel damage. B73 and Mo17 are the source of the most commercial valuable
      maize inbred lines in temperate zones, while the intermated B73 x Mo17 (IBM)
      population is an invaluable source for QTL identification. However, no or few
      experiments have been carried out to detect QTL for corn borer resistance in the
      B73 x Mo17 population. The objective of this work was to locate QTL for
      resistance to stem tunneling and kernel damage by MCB in the IBM population. We
      detected a QTL for kernel damage at bin 8.05, although the effect was small and
      two QTL for stalk tunneling at bins 1.06 and 9.04 in which the additive effects
      were 4 cm, approximately. The two QTL detected for MCB resistance were close to
      other QTL consistently found for European corn borer (ECB, Ostrinia nubilalis
      Hubner) resistance, indicating mechanisms of resistance common to both pests or
      gene clusters controlling resistance to different plagues. The precise mapping
      achieved with the IBM population will facilitate the QTL pyramiding and the
      positional cloning of the detected QTL.

PMID- 19756473
TI  - Development of wheat lines carrying stem rust resistance gene Sr39 with reduced
      Aegilops speltoides chromatin and simple PCR markers for marker-assisted
      selection.
AB  - The use of major resistance genes is a cost-effective strategy for preventing
      stem rust epidemics in wheat crops. The stem rust resistance gene Sr39 provides
      resistance to all currently known pathotypes of Puccinia graminis f. sp. tritici
      (Pgt) including Ug99 (TTKSK) and was introgressed together with leaf rust
      resistance gene Lr35 conferring adult plant resistance to P. triticina (Pt), into
      wheat from Aegilops speltoides. It has not been used extensively in wheat
      breeding because of the presumed but as yet undocumented negative agronomic
      effects associated with Ae. speltoides chromatin. This investigation reports the
      production of a set of recombinants with shortened Ae. speltoides segments
      through induction of homoeologous recombination between the wheat and the Ae.
      speltoides chromosome. Simple PCR-based DNA markers were developed for resistant
      and susceptible genotypes (Sr39#22r and Sr39#50s) and validated across a set of
      recombinant lines and wheat cultivars. These markers will facilitate the
      pyramiding of ameliorated sources of Sr39 with other stem rust resistance genes
      that are effective against the Pgt pathotype TTKSK and its variants.

PMID- 19756474
TI  - QTL mapping for adult-plant resistance to stripe rust in Italian common wheat
      cultivars Libellula and Strampelli.
AB  - Italian common wheat cultivars Libellula and Strampelli, grown for over three
      decades in Gansu province of China, have shown effective resistance to stripe
      rust. To elucidate the genetic basis of the resistance, F(3) populations were
      developed from crosses between the two cultivars and susceptible Chinese wheat
      cultivar Huixianhong. The F(3) lines were evaluated for disease severity in
      Beijing, Gansu and Sichuan from 2005 to 2008. Joint- and single-environment
      analyses by composite interval mapping identified five quantitative trait loci
      (QTLs) in Libellula for reduced stripe rust severity, designated QYr.caas-2DS,
      QYr.caas-4BL, QYr.caas-5BL.1, QYr.caas-5BL.2 and QYr.caas-7DS, and explained 8.1
      12.4, 3.6-5.1, 3.4-8.6, 2.6 and 14.6-35.0%, respectively, of the phenotypic
      variance across four environments. Six interactions between different pairs of
      QTLs explained 3.2-7.1% of the phenotypic variance. The QTLs QYr.caas-4BL,
      QYr.caas-5BL.1 and QYr.caas-7DS were also detected in Strampelli, explaining 4.5,
      2.9-5.5 and 17.1-39.1% of phenotypic variance, respectively, across five
      environments. Three interactions between different pairs of QTLs accounted for
      6.1-35.0% of the phenotypic variance. The QTL QYr.caas-7DS flanked by markers
      csLV34 and Xgwm295 showed the largest effect for resistance to stripe rust.
      Sequence analyses confirmed that the lines with the QYr.caas-7DS allele for
      resistance carried the resistance allele of the Yr18/Lr34 gene. Our results
      indicated that the adult-plant resistance gene Yr18 and several minor genes
      confer effective durable resistance to stripe rust in Libellula and Strampelli.

PMID- 19756475
TI  - Genetic variants of HvCbf14 are statistically associated with frost  tolerance in
      a European germplasm collection of Hordeum vulgare.
AB  - Two quantitative trait loci (Fr-H1 and Fr-H2) for frost tolerance (FT) have been
      discovered on the long arm of chromosome 5H in barley. Two tightly linked groups
      of CBF genes, known to play a key role in the FT regulatory network in A.
      thaliana, have been found to co- segregate with Fr-H2. Here, we investigate the
      allelic variations of four barley CBF genes (HvCbf3, HvCbf6, HvCbf9 and HvCbf14)
      in a panel of European cultivars, landraces and H. spontaneum accessions. In the
      cultivars a reduction of nucleotide and haplotype diversities in CBFs compared
      with the landraces and the wild ancestor H. spontaneum, was evident. In
      particular, in cultivars the loss of HvCbf9 genetic variants was higher compared
      to other sequences. In order to verify if the pattern of CBF genetic variants
      correlated with the level of FT, an association procedure was adopted. The
      pairwise analysis of linkage disequilibrium (LD) among the genetic variants in
      four CBF genes was computed to evaluate the resolution of the association
      procedure. The pairwise plotting revealed a low level of LD in cultivated
      varieties, despite the tight physical linkage of CBF genes analysed. A structured
      association procedure based on a general liner model was implemented, including
      the variants in CBFs,of Vrn-H1, and of two reference genes not involved in FT
      (alpha-Amy1 and Gapdh) and considering the phenotypic data for FT. Association
      analysis recovered two nucleotide variants of HvCbf14 and one nucleotide variant
      of Vrn-H1 as statistically associated to FT.

PMID- 19756476
TI  - Development and evaluation of single-nucleotide polymorphism  markers in
      allotetraploid rapeseed (Brassica napus L.).
AB  - Single-nucleotide polymorphisms (SNPs) and insertion-deletions (INDELs) are
      currently the important classes of genetic markers for major crop species. In
      this study, methods for developing SNP markers in rapeseed (Brassica napus L.)
      and their in silico mapping and use for genotyping are demonstrated. For the
      development of SNP and INDEL markers, 181 fragments from 121 different gene
      sequences spanning 86 kb were examined. A combination of different selection
      methods (genome-specific amplification, hetero-duplex analysis and sequence
      analysis) allowed the detection of 18 singular fragments that showed a total of
      87 SNPs and 6 INDELs between 6 different rapeseed varieties. The average
      frequency of sequence polymorphism was estimated to be one SNP every 247 bp and
      one INDEL every 3,583 bp. Most SNPs and INDELs were found in non-coding regions.
      Polymorphism information content values for SNP markers ranged between 0.02 and
      0.50 in a set of 86 varieties. Using comparative genetics data for B. napus and
      Arabidopsis thaliana, an allocation of SNP markers to linkage groups in rapeseed
      was achieved: a unique location was determined for seven gene sequences; two and
      three possible locations were found for six and four sequences, respectively. The
      results demonstrate the usefulness of existing genomic resources for SNP
      discovery in rapeseed.

PMID- 19756477
TI  - Allelic genome structural variations in maize detected by array comparative
      genome hybridization.
AB  - DNA polymorphisms such as insertion/deletions and duplications affecting genome
      segments larger than 1 kb are known as copy-number variations (CNVs) or
      structural variations (SVs). They have been recently studied in animals and
      humans by using array-comparative genome hybridization (aCGH), and have been
      associated with several human diseases. Their presence and phenotypic effects in
      plants have not been investigated on a genomic scale, although individual
      structural variations affecting traits have been described. We used aCGH to
      investigate the presence of CNVs in maize by comparing the genome of 13 maize
      inbred lines to B73. Analysis of hybridization signal ratios of 60,472 60-mer
      oligonucleotide probes between inbreds in relation to their location in the
      reference genome (B73) allowed us to identify clusters of probes that deviated
      from the ratio expected for equal copy-numbers. We found CNVs distributed along
      the maize genome in all chromosome arms. They occur with appreciable frequency in
      different germplasm subgroups, suggesting ancient origin. Validation of several
      CNV regions showed both insertion/deletions and copy-number differences. The
      nature of CNVs detected suggests CNVs might have a considerable impact on plant
      phenotypes, including disease response and heterosis.

PMID- 19756478
TI  - Combined randomised controlled trial experience of malignancies in studies using
      insulin glargine.
AB  - AIMS/HYPOTHESIS: Recent publications of data extracted from population registries
      have suggested a possible relationship between treatment with insulin glargine
      and increased incidence of cancer/breast cancer. The aim of the present study was
      investigate this possible relationship using data from the manufacturer's (sanofi
      aventis) pharmacovigilance database. METHODS: We analysed the manufacturer's
      (sanofi-aventis) pharmacovigilance database for all randomised clinical trials
      (RCTs; Phase 2-4) comparing insulin glargine with any comparator in type 1 or
      type 2 diabetes. We identified all serious adverse events coded under the System
      Organ Class of 'neoplasms, benign, malignant and unspecified'. Treatment-emergent
      neoplasms judged to be malignant were included in this analysis. RESULTS: The
      database included 31 studies, 12 in type 1 diabetes and 19 in type 2 diabetes.
      Twenty compared insulin glargine with NPH insulin, 29 were parallel-group studies
      and two had a crossover design. Studies were generally of 6 months' duration,
      except for trial reference number 4016 (n = 1,017), which had a duration of 5
      years. Overall, 10,880 people were included in the analysis (insulin glargine,
      5,657; comparator, 5,223). Forty-five people (0.8%) vs 46 people (0.9%) reported
      52 and 48 cases of malignant cancer in the insulin glargine and comparator
      groups, respectively (RR 0.90, 95% CI 0.60-1.36). Skin (12 people with 16 events
      vs six people with seven events, RR 1.85, 95% CI 0.69-4.92), colon and rectum
      (six vs ten people, RR 0.55, 95% CI 0.20-1.52), breast (four vs six people, RR
      0.62, 95% CI 0.17-2.18) and gastrointestinal tract (six vs four people, RR 1.38,
      95% CI 0.39-4.90) were the most commonly reported sites.
      CONCLUSIONS/INTERPRETATION: In these 31 RCTs, insulin glargine was not associated
      with an increased incidence of cancer, including breast cancer, compared with the
      comparator group.

PMID- 19756479
TI  - Contact frequency determines outcome of basal insulin initiation trials in type 2
      diabetes.
AB  - AIMS/HYPOTHESIS: The aim of the present study was to investigate whether
      predetermined contact frequency with the study team and endpoint insulin dose are
      associated with study outcomes in basal insulin initiation trials in type 2
      diabetes. METHODS: A systematic Medline search was performed. Using data from the
      selected studies, contact frequency was plotted against HbA(1c) reduction and
      endpoint insulin dose. The importance of face-to-face vs telephone contact was
      also analysed. Insulin dose was plotted against HbA(1c) reduction, hypoglycaemia
      rate and weight gain. To investigate non-specific study effects, the relationship
      between contact frequency and HbA(1c) was also assessed in dipeptidyl peptidase-4
      (DPP-4) inhibitor trials. RESULTS: The reduction in HbA(1c) was highly correlated
      with contact frequency and endpoint insulin dose (r (2) = 0.751, p < 0.001 and r
      (2) = 0.433, p = 0.008, respectively). However, after adjusting for contact
      frequency, the relationship between insulin dose and HbA(1c) reduction was no
      longer significant (p = 0.270). The frequency of both clinical and telephone
      contacts were independent predictors of HbA(1c) improvement (p = 0.010 and p <
      0.001, respectively). We found no dose-response relationship between end-of-study
      insulin dose and hypoglycaemia or weight gain. In DPP-4 inhibitor studies,
      contact frequency was not positively associated with HbA(1c).
      CONCLUSIONS/INTERPRETATION: The frequency of contact with the study team is
      highly correlated with the improvement in HbA(1c) achieved in basal insulin
      initiation trials in type 2 diabetic patients. This has important implications
      for trial design and interpretation, as well as for clinical care.

PMID- 19756480
TI  - Diagnosing diabetes--time for a change?

PMID- 19756481
TI  - Effect of type 2 diabetes on mortality risk associated with end-stage kidney
      disease.
AB  - AIMS/HYPOTHESIS: Patients with end-stage kidney disease (ESKD) and patients with
      diabetes mellitus experience higher mortality rates than the general population.
      Whether ESKD imparts the same excess in mortality risk for those with diabetes as
      it does for those without diabetes is unknown. METHODS: Included in the study
      were all white patients aged > or =25 years with incident ESKD and type 2
      diabetes (n = 4,141) or with incident ESKD but without diabetes (n = 13,289) in
      Australia from 1991 to 2005, and all the individuals aged > or =25 years without
      ESKD and with type 2 diabetes (n = 909) or without ESKD without diabetes (n =
      10,302) enrolled in the AusDiab Study--a nationwide Australian representative
      cohort--from 1999 to 2005. Excess mortality was analysed in patients with ESKD by
      diabetes status, using age-, sex- and diabetes-status-specific standardised
      mortality ratios (SMRs) in the first 8 years after first renal replacement
      therapy among ANZDATA patients relative to AusDiab participants. RESULTS: The
      SMRs in patients with ESKD were, in non-diabetic patients and in those with type
      2 diabetes, respectively: 14.2 (95% CI 13.9-14.6) and 10.8 (95% CI 10.4-11.2) (p
      < 0.01); in people aged <60 years, 28.7 (95% CI 27.2-30.4) and 18.6 (95% CI 17.1
      20.4) (p < 0.01); in people aged > or =60 years, 12.5 (95% CI 12.1-12.9) vs 9.7
      (95% CI 9.3-10.1) (p < 0.01); in men, 11.0 (95% CI 10.7-11.4) vs 8.9 (95% CI 8.4
      9.3) (p < 0.01); and in women, 23.4 (95% CI 22.5-24.3) vs 16.2 (95% CI 15.2-17.3)
      (p < 0.01). CONCLUSIONS/INTERPRETATION: ESKD was associated with a greater
      relative increase in mortality in the non-diabetic study populations than in the
      type 2 diabetes population. Excess mortality was greater among younger people and
      women.

PMID- 19756482
TI  - Insulin-mediated cortical activity in the slow frequency range is diminished in
      obese mice and promotes physical inactivity.
AB  - AIMS/HYPOTHESIS: There is evidence from mouse models and humans that alterations
      in insulin action in the brain are accompanied by an obese phenotype; however,
      the impact of insulin with regard to behavioural aspects such as locomotion is
      unknown. METHODS: To address insulin action in the brain with regard to cortical
      activity in distinct frequency bands and the behavioural consequences, the
      insulin signalling pathway was followed from the receptor to electrical activity
      and locomotion. Western blot analysis, electrocorticograms with
      intracerebroventricular (i.c.v.) application of insulin, and measurements of
      locomotor activity were performed in lean and obese, as well as Toll-like
      receptor (TLR) 2/4-deficient, mice. RESULTS: We show that insulin application
      i.c.v. into lean mice was accompanied by a profound increase in cortical activity
      in the slow frequency range, while diet-induced obese mice displayed insulin
      resistance. In parallel, insulin administered i.c.v. increased locomotor activity
      in lean mice, whereas a phosphatidylinositol-3 (PI3) kinase inhibitor or obesity
      abolished insulin-mediated locomotion. A potential candidate that links insulin
      signalling to locomotion is the Kv1.3 channel that is activated by PI3-kinase.
      Pharmacological inhibition of Kv1.3 channels that bypassed insulin receptor
      activation promoted activity. Moreover, mice deficient in TLR2/4-dependent
      signalling displayed an increase in cortical activity in the slow frequency range
      that was correlated with improved spontaneous and insulin-mediated locomotor
      activity. CONCLUSIONS/INTERPRETATION: Our data provide functional evidence for a
      direct effect of insulin on brain activation patterns in the slow frequency bands
      and locomotor activity in lean mice, while in obese mice, insulin-mediated
      locomotion is blunted and further aggravates physical inactivity.

PMID- 19756483
TI  - Medial arterial calcification in diabetes and its relationship to neuropathy.
AB  - Calcification of the media of arterial walls is common in diabetes and is
      particularly associated with distal symmetrical neuropathy. Arterial
      calcification also complicates chronic kidney disease and is an independent risk
      factor for cardiovascular and all-cause mortality. The term calcification is not
      strictly accurate because the morphological changes incorporate those of new bone
      formation, i.e. ossification. The processes are complex, but are closely related
      to those involved in bone homeostasis, and it is relevant that calcification of
      the arterial wall and osteopenia often co-exist. One particular factor linked to
      the development of arterial calcification is distal symmetrical neuropathy;
      indeed, it has been suggested that neuropathy explains the distal distribution of
      arterial calcification in diabetes. It has also been suggested that the link with
      neuropathy results from loss of neuropeptides, such as calcitonin gene-related
      peptide, which are inherently protective. The association between distal
      symmetrical neuropathy and calcification of the arterial wall highlights the fact
      that neuropathy may be an independent risk factor for cardiovascular mortality.

PMID- 19756484
TI  - Beta cell (dys)function in non-diabetic offspring of diabetic patients.
AB  - AIMS/HYPOTHESIS: The first-degree offspring of patients with type 2 diabetes are
      prone to develop type 2 diabetes, and have both insulin resistance and beta cell
      impairment. However, it is still unclear whether both pathophysiological features
      are inseparably combined and which is the outstanding determinant in the
      offspring. METHODS: Glucose metabolism, insulin sensitivity (calculated as M
      value divided by insulin [M/I]) and beta cell function were studied in the
      offspring of individuals with type 2 diabetes (n = 187; 57% females; age 43.8 +/-
      8.1 years; BMI 26.8 +/- 4.5 kg/m(2)) and in individuals without a family history
      of type 2 diabetes (controls, n = 519, 55% females; age 43.4 +/- 8.2 years; BMI
      26.4 +/- 3.7 kg/m(2), no significant differences between the groups for any
      characteristic) by performance of 75 g OGTT and 2 h hyperinsulinaemic (40 mU min(
      1) m(-2))-isoglycaemic clamp tests. Beta cell function was evaluated by
      calculating insulinogenic index (IGI) from C-peptide AUC:glucose AUC ratios from
      the first hour of OGTT (IGI[60 min]) and from the total OGTT (IGI[120 min]).
      RESULTS: During the OGTT, the offspring of individuals with type 2 diabetes
      showed 4-14% higher plasma glucose from 30 to 120 min (p < 0.05) and 20-29%
      higher serum insulin from 90 to 120 min, but decreased IGI(60 min) and IGI(120
      min) (p < 0.05). M/I was 11% lower in the offspring of affected individuals than
      in controls (p < 0.01). To study the offspring of patients with type 2 diabetes
      with insulin sensitivity similar to that of the control group, the offspring of
      affected patients were divided into M/I quartiles. Those in the third M/I
      quartile showed M/I values and major anthropometric characteristics similar to
      those of the controls, but insulin AUC and C-peptide AUC values were lower in the
      first hour and the total OGTT (p < 0.05). The third M/I quartile had lower IGI
      values at 60 min and 120 min: 11% and 14% lower, respectively (p < 0.02).
      CONCLUSIONS/INTERPRETATION: The first-degree offspring of type 2 diabetic
      patients show insulin resistance and beta cell dysfunction in response to oral
      glucose challenge. Beta cell impairment exists in insulin-sensitive offspring of
      patients with type 2 diabetes, suggesting beta cell dysfunction to be a major
      defect determining diabetes development in diabetic offspring.

PMID- 19756485
TI  - Seasonality of birth in adult type 2 diabetic patients in three Ukrainian
      regions.

PMID- 19756486
TI  - Biochemical and histological effects of exendin-4 (exenatide) on the rat
      pancreas.
AB  - AIMS/HYPOTHESIS: Exendin-4 is a 39 amino acid agonist of the glucagon-like
      peptide receptor and has been approved for treatment of type 2 diabetes. Many
      reports describe an increased incidence of acute pancreatitis in humans treated
      with exendin-4 (exenatide). Previous studies have evaluated the effect of exendin
      4 on beta cells and beta cell function. We evaluated the histological and
      biochemical effects of exendin-4 on the pancreas in rats. METHODS: We studied 20
      Sprague-Dawley male rats, ten of which were treated with exendin-4 and ten of
      which were used as controls. The study period was 75 days. Serum and pancreatic
      tissue were removed for biochemical and histological study. Blood glucose,
      amylase, lipase, insulin and adipocytokines were compared between the two groups.
      RESULTS: Animals treated with exendin-4 had more pancreatic acinar inflammation,
      more pyknotic nuclei and weighed significantly less than control rats. They also
      had higher serum lipase than control animals. Exendin-4 treatment was associated
      with lower insulin and leptin levels as well as lower HOMA values than in the
      untreated control group. CONCLUSIONS/INTERPRETATION: Although the use of exendin
      4 in rats is associated with decreased weight gain, lower insulin resistance and
      lower leptin levels than in control animals, extended use of exendin-4 in rats
      leads to pancreatic acinar inflammation and pyknosis. This raises important
      concerns about the likelihood of inducing acute pancreatitis in humans receiving
      incretin mimetic therapy.

PMID- 19756487
TI  - Interferon regulatory factor-1 is a key transcription factor in murine beta cells
      under immune attack.
AB  - AIMS/HYPOTHESIS: IFN-gamma, together with other inflammatory cytokines such as IL
      1beta and TNF-alpha, contributes to beta cell death in type 1 diabetes. We
      analysed the role of the transcription factor interferon regulatory factor (IRF)
      1, a downstream target of IFN-gamma/signal transducer and activator of
      transcription (STAT)-1, in immune-mediated beta cell destruction. METHODS: Islets
      from mice lacking Irf-1 (Irf-1 (-/-)) and control C57BL/6 mice were transplanted
      in overtly diabetic NOD mice. Viability and functionality of islets were
      evaluated in vitro. Chemokine expression by Irf-1 (-/-) islets and INS-1E cells
      transfected with Irf-1 short interfering RNA (siRNA) was measured by real-time
      PCR as well as in functional assays in vitro. RESULTS: IRF-1 deletion in islets
      was associated with higher prevalence of primary non-function (63% vs 25%, p <or=
      0.05) and shorter functioning graft survival (6.0 +/- 2.6 vs 10.4 +/- 4.8 days, p
      <or= 0.05) in contrast to similar skin graft survival. Although Irf-1 (-/-)
      islets were resistant to cytokine-induced cell death, insulin secretion by them
      was lower than that of control C57BL/6 islets under medium and cytokine
      conditions. IL-1 receptor antagonist partly restored the cytokine-induced
      secretory defect in vitro and completely prevented primary non-function in vivo.
      Cytokine-exposed Irf-1 (-/-) islets and INS-1E cells transfected with Irf-1 siRNA
      showed increased expression of Mcp-1 (also known as Ccl2), Ip-10 (also known as
      Cxcl10), Mip-3alpha (also known as Ccl20) and Inos (also known as Nos2) mRNA and
      elevated production of monocyte chemoattractant protein-1 (MCP-1) and nitrite
      compared with controls. In vivo, Irf-1 (-/-) islets displayed a higher potential
      to attract immune cells, reflected by more aggressive immune infiltration in the
      grafted islets. CONCLUSIONS/INTERPRETATION: These data indicate a key regulatory
      role for IRF-1 in insulin and chemokine secretion by pancreatic islets under
      inflammatory attack.

PMID- 19756488
TI  - Correlation of the leptin:adiponectin ratio with measures of insulin resistance
      in non-diabetic individuals.
AB  - AIMS/HYPOTHESIS: Obesity is the dominant cause of insulin resistance. In adult
      humans it is characterised by a combination of adipocyte hypertrophy and, to a
      lesser extent, adipocyte hyperplasia. As hypertrophic adipocytes secrete more
      leptin and less adiponectin, the plasma leptin:adiponectin ratio (LAR) has been
      proposed as a potentially useful measure of insulin resistance and vascular risk.
      We sought to assess the usefulness of the LAR as a measure of insulin resistance
      in non-diabetic white adults. METHODS: Leptin and adiponectin levels were
      measured in 2,097 non-diabetic individuals from the Ely and European Group for
      the Study of Insulin Resistance (EGIR) Relationship between Insulin Sensitivity
      and Cardiovascular Risk (RISC) study cohorts. LAR was compared with fasting
      insulin and HOMA-derived insulin sensitivity (HOMA-S) in all individuals and with
      the insulin sensitivity index (M/I) from hyperinsulinaemic-euglycaemic clamp
      studies in 1,226 EGIR RISC participants. RESULTS: The LAR was highly correlated
      with HOMA-S in men (r = -0.58, p = 4.5 x 10(-33) and r = -0.65, p = 1.1 x 10(-66)
      within the Ely and EGIR RISC study cohorts, respectively) and in women (r = 
      0.51, p = 2.8 x 10(-36) and r = -0.61, p = 2.5 x 10(-73)). The LAR was also
      strongly correlated with the clamp M/I value (r = -0.52, p = 4.5 x 10(-38) and r
      = -0.47, p = 6.6 x 10(-40) in men and women, respectively), similar to
      correlations between HOMA-S and the M/I value. CONCLUSIONS/INTERPRETATION: The
      leptin:adiponectin ratio is a useful measure of insulin resistance in non
      diabetic white adults. These data highlight the central role of adipocyte
      dysfunction in the pathogenesis of insulin resistance. Given that variations
      between fasting and postprandial leptin and adiponectin levels tend to be small,
      the leptin to adiponectin ratio might also have potential value in assessing
      insulin sensitivity in the non-fasted state.

PMID- 19756490
TI  - [Interdisciplinary treatment. Long-lasting, effective, and cost-effective].
AB  - The efficacy of intensive interdisciplinary pain management programs for patients
      with chronic low back pain has been repeatedly demonstrated. A controversial
      issue in previous studies is the cost-effectiveness of this treatment. Between
      2001 and 2006, a total of 575 patients with chronic nonspecific back pain took
      part in an outpatient pain management program at the German Red Cross Pain Center
      (DRK Schmerz-Zentrum Mainz) in Mainz, Germany. Complete follow-up data were
      available for 351 patients 1 year after the end of treatment and were included in
      the study. No differences between these patients and the dropouts were found.
      Pain, impairment, and mental well-being had significantly improved after 1 year.
      For employed patients, the number of absent days decreased to almost one-quarter.
      On the basis of the study by Wenig, who calculated pain-related costs as a
      function of Von Korff pain grades, the treatment resulted in a savings of euro
      3,329.50 per year per patient. Intensive multidisciplinary treatment of chronic
      back pain is highly effective and, at least for patients with high levels of
      disability, is also cost-effective.

PMID- 19756491
TI  - [Conservative strategies for treating low back pain].
AB  - This article discusses the importance of a careful patient history and a detailed
      clinical assessment to differentiate etiologic factors concerning the cause and
      continuation of low back pain. The indications and efficacy of various
      physiotherapeutic and balneological strategies are presented, with emphasis on
      the economic necessity of a targeted plan of care.

PMID- 19756492
TI  - [Risks and side effects of blood transfusion].
AB  - While transfusion of blood components is usually safe, there are risks of adverse
      effects that can have immunologic, nonimmunologic, or infectious causes. In
      patients, the fear of infectious disease transmission predominates, although the
      risk has been extremely low since the introduction of reliable serologic and
      molecular biological testing methods. This article addresses the incidence,
      clinical picture, and etiology of adverse effects of transfusion. It also reports
      on current knowledge concerning transfusion-associated acute lung injury, which
      has gained much attention in the last few years. Besides hepatitis and human
      immunodeficiency viruses, cytomegalovirus, parvovirus B19, prion transmission,
      and the risk of variant Creutzfeld-Jakob disease are also discussed.

PMID- 19756493
TI  - [Peri-operative adjustment and treatment of diabetes mellitus].
AB  - In all disciplines of operative medicine the number of patients who suffer from
      diabetes mellitus is increasing dramatically. The reason is that nowadays up to
      10% of the population is suffering from this disease. These patients must be
      treated with respect to the diabetes and also subsequent related conditions to
      prevent peri-operative complications. A special problem is that many patients do
      not know that they are suffering from diabetes. Pre-operatively and during the
      peri-operative course the coordinated efforts of surgeons, anaesthesiologists and
      diabetes specialists are essential to reach an optimal result. In all hospitals
      obligatory algorithms must be established for the treatment of these patients.

PMID- 19756494
TI  - [Treatment of postoperative thrombosis].
AB  - For the treatment of deep vein thrombosis (DVT), rapid diagnosis and prompt
      therapy are crucial to minimize the risk of fatal pulmonary embolism and long
      term complications, including the postthrombotic syndrome and recurrent
      thromboembolism. The treatment of acute DVT remains controversial. In this
      review, treatment options in relation to exposing and predisposing risk factors
      are discussed. Evidence-based data and recommendations from official guidelines
      are presented.

PMID- 19756495
TI  - [Diagnosis and treatment of foreign-body-associated infection in orthopaedic
      surgery].
AB  - Periprosthetic infection is a foreign-body-associated infection that is
      characterised by delayed osteomyelitis of bone tissue surrounding artificial
      joint replacement. Most of these infections result from intraoperative bacterial
      contamination of the prosthetic device implanted. The period from contamination
      to clinically apparent infection can last months or even years. In these cases,
      the initial surgical procedure is often not blamed for the actual infection.
      Moreover, these infections often produce minimal symptoms that can be mistaken
      for aseptic loosening of the artificial joint replacement. The bacterial burden
      of the causative pathogen is low in these cases, a fact that need to be
      considered in the diagnostic procedures.Knowledge of the pathogenesis allows the
      orthopaedic surgeon to plan the diagnostic procedures and therapy as well. In
      this context, the pathogen's ability to form biofilm is of crucial significance
      and explains why it is necessary to remove the foreign body (prosthesis or other
      artificial devices, such as material used for osteosynthesis or spinal
      stabilisation) to control this type of infection. This article gives some basic
      information for better understanding of foreign-body-associated infection in
      order to improve diagnostics and therapy in the clinical routine.

PMID- 19756496
TI  - Bacillus anthracis cell wall produces injurious inflammation but paradoxically
      decreases the lethality of anthrax lethal toxin in a rat model.
AB  - OBJECTIVES: The in vivo inflammatory effects of the Bacillus anthracis cell wall
      are unknown. We therefore investigated these effects in rats and, for comparison,
      those of known inflammatory stimulants, Staphylococcus aureus cell wall or
      lipopolysaccharide (LPS). METHOD AND RESULTS: Sprague-Dawley rats (n = 103) were
      challenged with increasing B. anthracis cell wall doses (10, 20, 40, 80, or 160
      mg/kg) or diluent (control) as a bolus or 24-h infusion. The three highest bolus
      doses were lethal (20-64% lethality rates) as were the two highest infused doses
      (13% with each). Comparisons among lethal or nonlethal doses on other measured
      parameters were not significantly different, and these were combined for
      analysis. Over the 24 h after challenge initiation with lethal bolus or infusion,
      compared to controls, ten inflammatory cytokines and NO levels were increased and
      circulating neutrophils and platelets decreased (P <or= 0.05). Changes with
      lethal doses were greater than changes with nonlethal doses (P <or= 0.01). Lethal
      bolus or infusion doses produced hypotension or hypoxemia, respectively (P <or=
      0.05). The effects with B. anthracis cell wall were similar to those of S. aureus
      cell wall or LPS. However, paradoxically administration of B. anthracis cell wall
      or LPS decreased the lethality of concurrently administered B. anthracis lethal
      toxin (P < 0.0001 and 0.04, respectively). CONCLUSION: B. anthracis cell wall has
      the potential to produce inflammatory injury during anthrax infection clinically.
      However, understanding why cell wall or LPS paradoxically reduced lethality with
      lethal toxin may help understand this toxin's pathogenic effects.

PMID- 19756497
TI  - Vitamin D deficiency in the intensive care unit: an invisible accomplice to
      morbidity and mortality?
AB  - The association between vitamin D deficiency and chronic illness is well-known.
      Vitamin D deficiency has been associated with increased mortality in the general
      population. Despite this knowledge, vitamin D insufficiency is seldom considered
      and rarely replaced adequately, if at all, in critically ill patients in
      intensive care. We present a hypothetic model demonstrating how vitamin D
      deficiency may be an unrecognized contributor to adverse outcome in intensive
      care patients.

PMID- 19756498
TI  - Increased plasma thioredoxin levels in patients with sepsis: positive association
      with macrophage migration inhibitory factor.
AB  - PURPOSE: To establish the relationship between plasma levels of thioredoxin (Trx)
      and macrophage migration inhibitory factor (MIF) in systemic inflammatory stress
      syndrome (SIRS)/sepsis. METHODS: Enzyme-linked immunosorbent assay measurements
      of Trx, MIF, IL-6, -8, and -10 and enzyme-linked fluorescent assay determination
      of procalcitonin (PCT) in plasma from patients with SIRS/sepsis, neutropenic
      sepsis, healthy volunteers and pre-oesophagectomy patients. RESULTS: Thioredoxin
      was significantly higher in SIRS/sepsis patients [101.3 ng ml(-1), interquartile
      range (IQR) 68.7-155.6, n = 32] compared with that in healthy controls (49.5 ng
      ml(-1), IQR 31.4-71.1, P < 0.001, n = 17) or pre-oesophagectomy patients (40.5 ng
      ml(-1), IQR 36.9-63.2, P < 0.01, n = 7), but was not raised in neutropenics (n =
      5). MIF levels were also significantly higher in SIRS/sepsis patients (12.1 ng
      ml(-1), IQR 9.5-15.5, n = 35), but not in the neutropenic group, when compared
      with healthy controls (9.3 ng ml(-1), IQR 7.3-10.7, P < 0.01, n = 20). Trx levels
      correlated, positively, with MIF levels and APACHE II scores. Plasma levels of IL
      6, -8 and -10 and PCT increased significantly in patients with SIRS/sepsis (P <
      0.001) and with neutropenic sepsis, but did not correlate with Trx or MIF levels.
      CONCLUSION: Plasma levels of Trx, MIF, IL-6, -8, -10 and PCT were raised in
      patients with SIRS/sepsis. Comparisons between mediators suggest a unique
      correlation of Trx with MIF. Moreover, Trx and MIF differed from cytokines and
      PCT in that levels were significantly lower in patients with neutropenia compared
      with the main SIRS/sepsis group. By contrast, IL-8 and PCT levels were
      significantly greater in the neutropenic patient group. The link between MIF and
      Trx highlighted in this study has implications for future investigations into the
      pathogenesis of SIRS/sepsis.

PMID- 19756499
TI  - Conflicts in the ICU: perspectives of administrators and clinicians.
AB  - PURPOSE: The purpose of this study is to understand conflicts in the ICU setting
      as experienced by clinicians and administrators and explore methods currently
      used to resolve such conflicts when there may be discordance between clinicians
      and families, caregivers or administration. METHODS: Qualitative case study
      methodology using semi-structured interviews was used. The sample included
      community and academic health science centres in 16 hospitals from across the
      province of Ontario, Canada. A total of 42 participants including hospital
      administrators and ICU clinicians were interviewed. Participants were sampled
      purposively to ensure representation. RESULTS: The most common source of conflict
      in the ICU is a result of disagreement about the goals of treatment. Such
      conflicts arise between the ICU and referring teams (inter-team), among members
      of the ICU team (intra-team), and between the ICU team and patients'
      family/substitute decision-maker (SDM). Inter- and intra-team conflicts often
      contribute to conflicts between the ICU team and families. Various themes were
      identified as contributing factors that may influence conflict resolution
      practices as well as the various consequences and challenges of conflict
      situations. Limitations of current conflict resolution policies were revealed as
      well as suggested strategies to improve practice. CONCLUSIONS: There is
      considerable variability in dealing with conflicts in the ICU. Greater attention
      is needed at a systems level to support a culture aimed at prevention and
      resolution of conflicts to avoid increased sources of anxiety, stress and
      burnout.

PMID- 19756500
TI  - An assessment of acute kidney injury with modified RIFLE criteria in pediatric
      patients with severe burns.
AB  - OBJECTIVE: To apply the modified pediatric RIFLE criteria for severity of acute
      kidney injury (AKI) to pediatric burn ICU patients and to evaluate the overall
      incidence of AKI, risk factors for AKI and influence of AKI on outcome. DESIGN:
      Retrospective, descriptive cohort study. SETTING: 10-bed burn PICU facility.
      PATIENTS: All consecutive patients with a burn injury of 10% or more of total
      body surface area percentage (TBSA, %) admitted during a 2 year period.
      MEASUREMENTS AND RESULTS: Data of 123 patients were studied. The incidence of AKI
      was 45.5%. Patients with AKI tended to have higher mortality than those without
      AKI (p = 0.057). All nonsurvivors attained pRIFLE AKI by combination of serum
      creatinine and urine output criteria. Patients with a more severe form of AKI
      (Failure and Injury) as well as patients with late AKI had more episodes of
      sepsis as compared to patients with early AKI and the Risk category of AKI.
      Logistic regression analysis indicated that PRISM score and TBSA were the
      independent risk factors for acute kidney injury in pediatric burn patients; the
      presence of sepsis and septic shock were the independent risk factors for the
      Failure class of AKI. CONCLUSION: We observed a high incidence of AKI in the burn
      PICU population. Sepsis seems to contribute to the development of the Failure
      class of AKI. Maximum Failure class of AKI is associated with high mortality.

PMID- 19756501
TI  - Neutrophil and monocyte CD64 indexes,  lipopolysaccharide-binding protein, 
      procalcitonin and C-reactive protein in sepsis  of critically ill neonates and
      children.
AB  - OBJECTIVE: To compare the diagnostic accuracy of neutrophil and monocyte CD64
      indexes (CD64in and CD64im) for sepsis in critically ill neonates and children
      with that of lipopolysaccharide-binding protein (LBP), procalcitonin (PCT) and C
      reactive protein (CRP). DESIGN AND SETTING: Prospective, observational study in a
      level III multidisciplinary neonatal and pediatric intensive care unit (ICU).
      PATIENTS: Forty-six neonates and 36 children with systemic inflammatory response
      syndrome (SIRS) and suspected infection, classified into two groups: those with
      bacterial sepsis (microbiologically proven or clinical sepsis) and those without
      bacterial sepsis (infection not supported by subsequent clinical course,
      laboratory data and microbiological tests). INTERVENTIONS AND MEASUREMENTS: Flow
      cytometric CD64in and CD64im, serum LBP, PCT and CRP measurement on 2 consecutive
      days from admission to the ICU. RESULTS: There were 17 cases of bacterial sepsis
      in neonates and 24 cases of bacterial sepsis in children. All neonates and the
      majority of children were mechanically ventilated, and more than two-thirds of
      neonates with sepsis and one-third of children with sepsis needed
      inotropic/vasopressor drugs. The highest diagnostic accuracy for sepsis on the
      1st day of suspected sepsis was achieved by LBP in neonates (0.86) and by CD64in
      in children (0.88) and 24 h later by CD64in in neonates (0.96) and children
      (0.98). CONCLUSIONS: Neutrophil CD64 index (CD64in) is the best individual marker
      for bacterial sepsis in children, while in neonates the highest diagnostic
      accuracy at the time of suspected sepsis was achieved by LBP and 24 h later by
      CD64in.

PMID- 19756502
TI  - Frequency and clinical impact of preserved bispectral index activity during deep
      sedation in mechanically ventilated ICU patients.
AB  - OBJECTIVE: Despite an overall correlation between the bispectral index of the EEG
      (BIS) and clinical sedation assessment, unexpectedly high BIS values can be
      observed at deep sedation levels. We assessed the frequency, interindividual
      variability and clinical impact of high BIS values during clinically deep
      sedation. DESIGN AND SETTING: Prospective observational study in two university
      affiliated intensive care units. PATIENTS: Sixty-two mechanically ventilated
      patients requiring intravenous sedation and analgesia for >or=24 h. MEASUREMENTS
      AND MAIN RESULTS: Paired measurements of BIS and sedation measured on the
      adaptation to intensive care environment (ATICE) score were obtained every 3 h
      until awakening. A paired measurement with BIS >60 at deep sedation (ATICE
      Awakeness <or=2) was defined as discordant. Patients were considered discordant
      if their individual ratio of number of discordant measurements to number of total
      measurements during deep sedation was above the median discordance ratio of the
      overall cohort. At least one discordant assessment was observed in 52 patients
      (83.9%). Median individual discordance ratio was 32% (14.3-50.0%). Time from
      awakening to first T-piece trial [16 h (4-34) vs. 46 h (9-109), p = 0.01] and to
      extubation [35 h (23-89) vs. 88 h (46-152 h), p = 0.05] were significantly
      shorter in discordant compared to concordant patients. BIS-ATICE discordance was
      independently associated with successful extubation within 48 h after awakening
      (OR 6.7, CI 95% 1.8-25.0, p = 0.005). The rate of ICU recall was not different in
      BIS-ATICE discordant and concordant patients. CONCLUSIONS: In mechanically
      ventilated ICU patients, discordance between high BIS values and deep clinical
      sedation is frequently observed and may suggest faster weaning from the
      ventilator.

PMID- 19756503
TI  - Evaluation of "Loss" and "End stage renal disease" after acute kidney injury
      defined by the Risk, Injury, Failure, Loss and ESRD classification in critically
      ill patients.
AB  - PURPOSE: The Risk, Injury, Failure, Loss and ESRD (RIFLE) classification has been
      widely accepted for the definition of acute kidney injury (AKI); however, no
      study has described in detail the last two stages of the classification: "Loss"
      and "ESRD". We aim to describe and evaluate the development of "Loss" and "ESRD"
      in a group of critically ill patients. METHODS: We conducted a retrospective
      analysis of cases prospectively collected from the Acute Physiology and Chronic
      Health Assessment (APACHE III) database. Subjects were consecutive critically ill
      patients >18 years of age admitted to three ICUs of two tertiary care academic
      hospitals, from January 2003 through August 2006, excluding those who denied
      research authorization, chronic hemodialysis therapy, kidney transplant
      recipients, readmissions, and admissions for less than 12 h for low risk
      monitoring. RESULTS: 11,644 patients were included in the study. The median age
      was 66 (interquartile range, 52-76), 90% were Caucasians and 54% of the patients
      were male. Half of the patients developed AKI, and most of the patients were in
      the Risk and Injury stages. From the patients that developed AKI, a total of
      1,065 (19%) patients required renal replacement therapy (RRT), 415 (39%)
      underwent continuous renal replacement therapy (CRRT) and 650 (61%) underwent
      intermittent hemodialysis. A total of 281 patients on RRT did not survive
      hospital discharge, 97 patients progressed to "Loss", and 282 patients progressed
      to "ESRD". After multivariable adjustment, the progression to "ESRD" was
      associated with higher baseline creatinine, odds ratio (OR) 1.19 per every
      increase in creatinine of 0.1 mg/dl (95% CI, 1.11-1.29) P < 0.001; and less
      frequent use of CRRT, OR 0.18 (95% CI, 0.11-0.29) P < 0.001. CONCLUSION: In this
      large retrospective study we found that almost 50% developed some form of AKI as
      defined by the RIFLE classification. Of these, 19% required RRT, and 4.9%
      progressed to "ESRD". "ESRD" was more likely in patients with elevated baseline
      creatinine and those treated with intermittent hemodialysis.

PMID- 19756504
TI  - Acute abdomen and severe lactic acidosis can lead to a surprising diagnosis.

PMID- 19756505
TI  - Comparing two different arginine vasopressin doses in advanced vasodilatory
      shock: a randomized, controlled, open-label trial.
AB  - PURPOSE: To compare the effects of two arginine vasopressin (AVP) dose regimens
      on the hemodynamic response, catecholamine requirements, AVP plasma
      concentrations, organ function and adverse events in advanced vasodilatory shock.
      METHODS: In this prospective, controlled, open-label trial, patients with
      vasodilatory shock due to sepsis, systemic inflammatory response syndrome or
      after cardiac surgery requiring norepinephrine >0.6 microg/kg/min were randomized
      to receive a supplementary AVP infusion either at 0.033 IU/min (n = 25) or 0.067
      IU/min (n = 25). The hemodynamic response, catecholamine doses, laboratory and
      organ function variables as well as adverse events (decrease in cardiac index or
      platelet count, increase in liver enzymes or bilirubin) were recorded before, 1,
      12, 24 and 48 h after randomization. A linear mixed effects model was used for
      statistical analysis in order to account for drop-outs during the observation
      period. RESULTS: Heart rate and norepinephrine requirements decreased while MAP
      increased in both groups. Patients receiving AVP at 0.067 IU/min required less
      norepinephrine (P = 0.006) than those infused with AVP at 0.033 IU/min. Arterial
      lactate and base deficit decreased while arterial pH increased in both groups.
      During the observation period, AVP plasma levels increased in both groups (both P
      < 0.001), but were higher in the 0.067 IU/min group (P < 0.001) and in patients
      on concomitant hydrocortisone. The rate of adverse events and intensive care unit
      mortality was comparable between groups (0.033 IU/min, 52%; 0.067 IU/min, 52%; P
      = 1). CONCLUSIONS: A supplementary AVP infusion of 0.067 IU/min restores
      cardiovascular function in patients with advanced vasodilatory shock more
      effectively than AVP at 0.033 IU/min.

PMID- 19756506
TI  - The performance and customization of SAPS 3 admission score in a Thai medical
      intensive care unit.
AB  - PURPOSE: The aim of this study was to evaluate the performance of Simplified
      Acute Physiology Score 3 (SAPS 3) admission scores, both the original and a
      customized version, in mixed medical critically ill patients. METHODS: A
      prospective cohort study was conducted over a 2-year period in the medical
      intensive care unit (MICU) of a tertiary referral university teaching hospital in
      Thailand. The probability of hospital mortality of the original SAPS 3 was
      calculated using the general and customized Australasia version (SAPS 3-AUS). The
      patients were randomly divided into equal calibration and validation groups for
      customization. RESULTS: A total of 1,873 patients were enrolled. The hospital
      mortality rate was 28.6%. The general equation of SAPS 3 had excellent
      discrimination with an area under the receiver operating characteristic curve of
      0.933, but poor calibration with the Hosmer-Lemeshow goodness-of-fit H = 106.7
      and C = 101.2 (P < 0.001), and it overestimated mortality with a standardized
      mortality ratio of 0.86 (95% confidence interval, 0.79-0.93). The calibration of
      SAPS 3-AUS was also poor. The customized SAPS 3 showed a good calibration of all
      patients in the validation group (H = 14, P = 0.17 and C = 11.3, P = 0.33) and
      all subgroups according to main diagnosis, age, gender and co-morbidities.
      CONCLUSIONS: The SAPS 3 provided excellent discrimination but poor calibration in
      our MICU. A first level customization of the SAPS 3 improved the calibration and
      could be used to predict mortality and quality assessment in our ICU or other
      ICUs with a similar case mix.

PMID- 19756507
TI  - Comparison of four methods of lung volume  recruitment during high frequency
      oscillatory  ventilation.
AB  - PURPOSE: To compare four methods of volume recruitment upon initiation of high
      frequency oscillatory ventilation (HFOV). METHODS: Anesthetized intubated
      neonatal piglets (n = 10) underwent repeated saline lavage, followed by
      conventional mechanical ventilation (CMV). After transition to HFOV at a mean
      airway pressure 8 cmH2O above CMV (P(basal)), four methods of lung volume
      recruitment were tested in each animal in random order: Escalating--step-wise
      pressure increments over 6 min to a peak mean airway pressure 12 cmH2O above
      P(basal); Sustained dynamic inflation (DI)--a 20 s inflation to the same peak
      pressure; DI repeated six times for 1 s; Standard--mean airway pressure set
      directly at P(basal). After each recruitment method, HFOV continued at P(basal)
      for 15 min. Thoracic gas volume and distribution of aeration were determined by
      single slice computed tomography, and oxygenation by arterial blood gas sampling.
      RESULTS: Escalating recruitment resulted in the greatest thoracic gas volume 15
      min post recruitment [77 +/- 3.3% of total lung capacity vs. 70 +/- 4.2%
      (Sustained DI), 65 +/- 3.5% (Repeated DI),63 +/- 5.1% (Standard); mean +/- SEM; P
      = 0.042, ANOVA]. All methods resulted in a reduction in non-aerated lung, with
      the greatest redistribution to normally aerated lung being with Escalating
      recruitment. Oxygenation 15 min post recruitment was better with the Escalating
      method than with Repeated DI or Standard recruitment (pO2 307 +/- 41 vs. 159 +/-
      36 vs. 134 +/- 39 mmHg, respectively; P = 0.016, ANOVA). CONCLUSIONS: Escalating
      recruitment produced the greatest increase in lung volume and resolution of
      atelectasis, and is recommended for lung volume recruitment upon initiation of
      HFOV.

PMID- 19756508
TI  - Oxygen, temperature and humidity of inspired gases and their influences on airway
      and lung tissue in near-term lambs.
AB  - PURPOSE: The relative contributions of factors influencing lung injury
      immediately after birth are poorly understood. We hypothesized that oxygen
      content and humidity of inspired air would influence markers of pulmonary
      inflammation in ventilated lambs. METHODS: Lambs delivered at 140 days gestation
      (term = 150 days) were assigned to one of five groups (n = 5-6/group):
      unventilated controls, or ventilation with 21 or 100% O(2) that was either heated
      and humidified or cold and dry. Lambs were ventilated gently for 3 h: blood gases
      were recorded regularly. Bronchoalveolar lavage and samples of tracheal mucosa
      and lung were collected post mortem. RESULTS: Arterial pH was lower [mean
      difference (95% CI): -0.07 (-0.13, -0.03)], while there was an increase in
      PaCO(2) [mean difference (95% CI): 10.2 (2.4, 17.9)] and fold change in lung pro
      inflammatory IL-1beta cytokine mRNA [mean difference (95% CI): 28.3 (0.3, 56.2)]
      or IL-8 [mean difference (95% CI): 27.8 (7.9, 47.7)] cytokine mRNA expression
      with 100% O(2) relative to 21% O(2). Cold dry inspired gas did not influence gas
      exchange or dynamic mechanics at 3 h compared to heated humidified gas. Compared
      to 100% inspired O(2), cold dry inspired gas had less marked effect on fold
      change in lung pro-inflammatory IL-1beta cytokine mRNA [mean difference (95% CI):
      27.2 (-0/8, 55.1)] or IL-8 [mean difference (95% CI): 14.5 (5.5, 34.4)] cytokine
      mRNA expression, although cilial dysfunction/damage was evident on electron
      microscopy, especially when exposure to cold dry gas was combined with hyperoxia.
      CONCLUSIONS: In near-term neonatal lambs ventilated for 3 h, hyperoxia was
      associated a more powerful stimulus for pulmonary dysfunction and upregulation of
      inflammatory cytokines than cold dry gas.

PMID- 19756509
TI  - Determining the economic cost of ICU treatment: a prospective "micro-costing"
      study.
AB  - OBJECTIVE: To prospectively assess the cost of patients in an adult intensive
      care unit (ICU) using bottom-up costing methodology and evaluate the usefulness
      of "severity of illness" scores in estimating ICU cost. METHODS AND DESIGN: A
      prospective study costing 64 consecutive admissions over a 2-month period in a
      mixed medical/surgical ICU. RESULTS: The median daily ICU cost (interquartile
      range, IQR) was 2,205 euro (1,932 euro-3,073 euro), and the median total ICU cost
      (IQR) was 10,916 euro (4,294 euro-24,091 euro). ICU survivors had a lower median
      daily ICU cost at <euro>2,164 per day, compared with 3,496 euro per day for ICU
      non-survivors (P = 0.08). The requirements for continuous haemodiafiltration,
      blood products and anti-fungal agents were associated with higher daily and
      overall ICU costs (P = 0.002). Each point increase in SAPS3 was associated with a
      305 euro (95% CI 31 euro-579 euro) increase in total ICU cost (P = 0.029).
      However, SAPS3 accounted for a small proportion of the variance in this model (R
      (2) = 0.08), limiting its usefulness as a stand-alone predictor of cost in
      clinical practice. A model including haemodiafiltration, blood products and anti
      fungal agents explained 54% of the variance in total ICU cost. CONCLUSION: This
      bottom-up costing study highlighted the considerable individual variation in
      costs between ICU patients and identified the major factors contributing to cost.
      As the requirement for expensive interventions was the main driver for ICU cost,
      "severity of illness" scores may not be useful as stand-alone predictors of cost
      in the ICU.

PMID- 19756510
TI  - Assessment of clinical risk predictive rules for invasive candidiasis in a
      prospective multicentre cohort of ICU patients.
AB  - PURPOSE: To assess the generalisability of published clinical risk predictive
      models for invasive candidiasis in ICU patients. METHODS: The performance
      characteristics of published clinical risk factor-only and Candida colonisation
      only predictive models for invasive candidiasis were assessed in a multicentre
      cohort of Australian ICU patients. Clinical risk factors and Candida colonisation
      parameters were collected prospectively from patients. RESULTS: The two clinical
      risk factor-only predictive models applied to an Australian patient cohort (n =
      615) performed less well than in published studies involving derivation
      populations. Model performance characteristics improved when Candida colonisation
      parameters were added post-hoc. CONCLUSIONS: Risk predictive models should factor
      in both clinical risk factors and Candida colonisation parameters. Integrating
      these models into therapeutic algorithms first requires external validation in
      different patient populations and settings.

PMID- 19756511
TI  - Patients' memory and psychological distress after ICU stay compared with
      expectations of the relatives.
AB  - PURPOSE: To compare patients' psychological distress and memories from intensive
      care unit (ICU) treatment 4-6 weeks after ICU discharge with expectations of
      their relatives. Further, to explore the relationship between personality traits
      and ICU memories with psychological distress. METHODS: A cross-sectional study of
      255 patients and 298 relatives. The questionnaire included: hospital anxiety and
      depression scale (HADS), impact of event scale (IES), life orientation test, ICU
      memory tool and memory of ICU; technical procedures, pain, lack of control and
      inability to express needs. Relatives were assessed for their expectations of the
      patients' memories and psychological distress. RESULTS: Twenty-five percent of
      the patients reported severe posttraumatic stress symptoms, IES-total >or= 35.
      The levels of anxiety and depression were significantly higher than in the
      general population, mean anxiety was 5.6 versus 4.2 (p < 0.001), and mean
      depression was 4.8 versus 3.5 (p < 0.001). Relatives expected more psychological
      distress and the relatives thought the patient was less able to express needs
      than the patients reported (p < 0.001). Higher age, unemployment, respirator
      treatment, pessimism, memory of pain, lack of control and inability to express
      needs were independent predictors of posttraumatic stress symptoms (p < 0.01).
      CONCLUSIONS: Psychological distress symptoms were frequent among ICU survivors.
      Relatives expected the patients to be more distressed after ICU treatment than
      the patients reported. The strongest predictors of posttraumatic stress symptoms
      from the ICU were memoris about pain, lack of control and inability to express
      needs. Pessimism may be a reason for psychological distress and should be
      addressed during follow up, as pessimistic patients may need more motivation and
      support.

PMID- 19756512
TI  - Improved detection of blood stream pathogens by real-time PCR in severe sepsis.
AB  - OBJECTIVE: Evaluation of the technical and diagnostic feasibility of commercial
      multiplex real-time polymerase chain reaction (PCR) for detection of blood stream
      infections in a cohort of intensive care unit (ICU) patients with severe sepsis,
      performed in addition to conventional blood cultures. DESIGN: Dual-center cohort
      study. SETTING: Surgical ICU of two university hospitals. PATIENTS AND
      PARTICIPANTS: One hundred eight critically ill patients fulfilling the American
      College of Chest Physicians/Society of Critical Care Medicine (ACCP/SCCM) severe
      sepsis criteria were included. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: PCR
      results obtained in 453 blood samples from 108 patients were compared with
      corresponding blood culture results. PCR resulted in a twofold higher positivity
      rate when compared with conventional blood culture (BC) testing (114 versus 58
      positive samples). In 40 out of 58 PCR positive assays the results of the
      corresponding blood cultures were identical to microorganisms detected by PCR. In
      18 samples PCR and BC yielded discrepant results. Compared with conventional
      blood culture the sensitivity and specificity of PCR was 0.69 and 0.81,
      respectively. Further evaluation of PCR results against a constructed gold
      standard including conventional microbiological test results from other
      significant patient specimen (such as bronchio-alveolar lavage fluid, urine,
      swabs) and additionally generated clinical and laboratory information yielded
      sensitivity of 0.83 and specificity of 0.93. CONCLUSIONS: Our cohort study
      demonstrates improved pathogen detection using PCR findings in addition to
      conventional blood culture testing. PCR testing provides increased sensitivity of
      blood stream infection. Studies addressing utility including therapeutic decision
      making, outcome, and cost-benefit following diagnostic application of PCR tests
      are needed to further assess its value in the clinical setting.

PMID- 19756514
TI  - Does the combination of chondroitin sulfate and glucosamine  delay the cartilage
      destruction in ochronopathy?

PMID- 19756515
TI  - Cold-active halophilic bacteria from the ice-sealed Lake Vida, Antarctica.
AB  - Lake Vida is a large, permanently ice-covered lake in the Victoria Valley of the
      McMurdo Dry Valleys, Antarctica and is unique among Dry Valley lakes because it
      is ice-sealed, with an ice-cover of nearly 19 m. Enrichment cultures of melt
      water from Lake Vida 15.9 m ice yielded five pure cultures of aerobic,
      heterotrophic bacteria. Of these, one strain grew at -8 degrees C and the four
      others at -4 degrees C. All isolates were either halotolerant or halophilic, with
      two strains capable of growth at 15% NaCl. Phylogenetic analysis revealed the
      Lake Vida isolates to be Gammaproteobacteria, related to species of Psychrobacter
      and Marinobacter. This is the first report of pure cultures of bacteria from Lake
      Vida, and the isolates displayed a phenotype consistent with life in a cold
      hypersaline environment.

PMID- 19756516
TI  - Histochemical study of intestinal mucins after administration of silver
      nanoparticles in Sprague-Dawley rats.
AB  - To investigate the effects of silver nanoparticles on the histological structure
      and properties of the mucosubstances in the intestinal mucosa, Sprague-Dawley
      rats were divided into four groups (10 rats in each group): vehicle control, low
      dose group (30 mg/kg), middle-dose group (300 mg/kg), and high-dose group (1,000
      mg/kg), and administered silver nanoparticles (60 nm) for 28 days, following OECD
      test guideline 407 and using GLP. The control sections contained no silver
      nanoparticles; however, the treated samples showed luminal and surface particles
      and the tissue also contained silver nanoparticles. A dose-dependent increased
      accumulation of silver nanoparticles was observed in the lamina propria in both
      the small and large intestine, and also in the tip of the upper villi in the
      ileum and protruding surface of the fold in the colon. The silver nanoparticle
      treated rats exhibited higher numbers of goblet cells that had released their
      mucus granules than the controls, resulting in more mucus materials in the crypt
      lumen and ileal lumen. Moreover, cell shedding at the tip of the villi was
      frequent. Lower amounts of neutral and acidic mucins were found in the goblet
      cells in the silver nanoparticle-treated rats, plus the amount of sialomucins was
      increased, while the amount of sulfomucins was decreased. In particular, in the
      colon of the silver nanoparticle-treated rats, sialyated mucins were detected in
      the lamina propria, the connective tissue under the epithelia. Therefore, the
      present results suggest that silver nanoparticles induce the discharge of mucus
      granules and an abnormal mucus composition in the goblet cells in the intestines.

PMID- 19756518
TI  - Effect of gestational and lactational exposure to perfluorooctanesulfonate on
      calcium-dependent signaling molecules gene expression in rats' hippocampus.
AB  - Perfluorooctanesulfonate (PFOS) is an environmental contaminant found in human
      and animal tissues worldwide. The developing nervous system is thought to be
      particularly sensitive to PFOS by the fact that PFOS can cross blood-brain and
      placental barriers. Effect of gestational and lactational exposure to PFOS on
      central nervous system (CNS) in Wistar rats was investigated by the cross-foster
      model built with PFOS at 0 or 3.2 mg/kg food. Real-time reverse transcription
      polymerase chain reaction was employed to evaluate the gene expression of calcium
      dependent signaling molecules in rats' hippocampus which are critical to the
      function of CNS. The expression of calcium-related signaling molecules, such as N
      methyl-D-aspartate receptor subtype-2B (NR2B), calmodulin (CaM), Ca2+/calmodulin
      dependent kinase II alpha (CaMKIIalpha) and cAMP-response element-binding (CREB)
      were increased in the PFOS exposure group at postnatal day 1 (PND 1). The
      decreased NR2B in the prenatal PFOS exposure group, the decreased CaM in the pre
      /postnatal PFOS exposure group, the increased CaMKIIalpha in the whole-life PFOS
      exposure group and the increased CREB in the prenatal/whole-life PFOS exposure
      group was observed at PND 7. At PND 35, rats exhibited the decreased NR2B in the
      pre-/postnatal and the whole-life PFOS exposure group, and the decreased CaM in
      the postnatal PFOS group. The results indicate that perinatal exposure to PFOS
      during the critical period of development of the brain may have neurotoxic effect
      on CNS by mediating the molecules of calcium signaling pathway.

PMID- 19756519
TI  - Peripheral nerve injury up-regulates expression of interactor protein for
      cytohesin exchange factor 1 (IPCEF1) mRNA in rat dorsal root ganglion.
AB  - Interaction protein for cytohesin exchange factors 1 (IPCEF1) is a recently
      identified protein that binds to cytohesin 2 and might participate in membrane
      receptor trafficking by enhancing the activity of cytohesin 2 in cultured cells.
      However, whether IPCEF1 is involved in this process in vivo is unknown. Here, we
      report that IPCEF1 messenger RNA (mRNA) is expressed in the dorsal root ganglions
      (DRGs) of adult rats. Moreover, peripheral nerve injury induced by fifth spinal
      nerve ligation and transection or sciatic nerve transection significantly up
      regulated expression of IPCEF1 mRNA in the injured DRGs. Because peripheral nerve
      injury leads to changes in membrane receptor trafficking in the injured DRG, the
      correlation of IPCEF1 mRNA expression with nerve injury input in the injured DRG
      suggests that IPCEF1 might participate in the mechanisms that underlie nerve
      injury-induced membrane receptor trafficking in the DRG under neuropathic pain
      conditions.

PMID- 19756521
TI  - Modelling psychosis.

PMID- 19756522
TI  - Impulsivity and cigarette craving: differences across subtypes.
AB  - RATIONALE: Cigarette smoking has been linked to a number of personality
      characteristics, including impulsivity. Smokers tend to endorse high levels of
      impulsivity, and more impulsive smokers have greater difficulty quitting, but
      little is known about potential explanatory mechanisms. Although indirect
      evidence suggests craving as a candidate mechanism, direct evidence has been
      mixed. MATERIALS AND METHODS: This study assessed whether specific aspects of
      impulsivity (sensation seeking, lack of premeditation, lack of perseverance, and
      urgency) were associated with cue-induced craving. Regular smokers (n = 60; 50%
      female) were exposed to a smoking cue and a neutral cue in a repeated measure
      counter-balanced design. RESULTS: Mixed effects regression models indicated that
      smokers who were high in sensation seeking reported greater increases in
      appetitive craving after smoking cue exposure, whereas, smokers who were high in
      urgency and lack of perseverance reported greater increases in negative affect
      craving. CONCLUSIONS: Findings suggest a complex relationship between impulsivity
      and cue-induced craving that may be masked by single construct conceptualizations
      of impulsivity.

PMID- 19756523
TI  - Diminished brain 5-HT transporter binding in major depression: a positron
      emission tomography study with [11C]DASB.
AB  - BACKGROUND: The serotonin transporter (5-HTT) plays a critical role in the
      regulation of serotonin neurotransmission and has been implicated in the
      pathophysiology of major depression. In a previous positron emission tomography
      study, we found no difference in brain 5-HTT binding between unmedicated
      recovered depressed patients and healthy controls. AIM: This study aims to assess
      brain 5-HTT binding in a group of unmedicated acutely depressed patients in
      comparison to healthy controls. METHODS: We studied 5-HTT binding using
      [(11)C]DASB in conjunction with positron emission tomography in 12 medication
      free depressed patients with a mean duration of illness of about 1 year and 24
      healthy controls. RESULTS: The depressed patients had lowered 5-HTT binding in
      several brain regions including brain stem, thalamus, caudate, putamen, anterior
      cingulate cortex and frontal cortex. CONCLUSIONS: These results suggest that
      diminished availability of the 5-HTT in the brain may be a state marker of acute
      depression. Alternatively, low 5-HTT binding may delineate a group of depressed
      patients with a poor long-term prognosis.

PMID- 19756524
TI  - Neural basis for a heritable phenotype: differences in the effects of apomorphine
      on startle gating and ventral pallidal GABA efflux in male Sprague-Dawley and
      Long-Evans rats.
AB  - RATIONALE: Prepulse inhibition (PPI) of startle is a measure of sensorimotor
      gating that is heritable and deficient in certain psychiatric disorders,
      including schizophrenia. Sprague-Dawley (SD) rats are more sensitive to PPI
      disruptive effects of dopamine (DA) agonists at long interstimulus intervals (60
      120 ms) and less sensitive to their PPI-enhancing effects at short (10-30 ms),
      compared with Long-Evans (LE) rats. These heritable strain differences in
      sensitivity to the PPI disruptive effects of DA agonists must ultimately reflect
      neural changes "downstream" from forebrain DA receptors. OBJECTIVE: The current
      study evaluated the effects of the DA agonist, apomorphine (APO), on ventral
      pallidal (VP) gamma-aminobutyric acid (GABA) and glutamate efflux and PPI in SD
      and LE rats. METHODS: PPI was tested in SD and LE rats after vehicle or APO (0.5
      mg/kg, subcutaneously (s.c.)) in a within-subject design. In different SD and LE
      rats, VP dialysate was collected every 10 min for 120 min after vehicle or APO
      (0.5 mg/kg, s.c.) and analyzed for GABA and glutamate content by capillary
      electrophoresis (CE) coupled with laser-induced fluorescence (LIF). RESULTS: As
      predicted, SD rats exhibited greater APO-induced PPI deficits at long intervals
      and less APO-induced PPI enhancement at short intervals compared to LE rats. APO
      significantly reduced VP GABA efflux in SD but not in LE rats; glutamate efflux
      was unaffected in both strains. CONCLUSION: Heritable strain differences in PPI
      APO sensitivity in SD vs LE rats parallel, and may be mediated by, strain
      differences in the VP GABA efflux.

PMID- 19756525
TI  - A dopamine transport inhibitor with markedly low abuse liability suppresses
      cocaine self-administration in the rat.
AB  - RATIONALE: N-substituted benztropine analogs are potent dopamine uptake
      inhibitors that display pharmacokinetic/dynamic properties consistent with the
      profile of a substitute medication for cocaine addiction. OBJECTIVES: The purpose
      of the present experiments was to characterize in rats the addictive-like
      properties of one such analog, 3 alpha-[bis(4'-fluorophenyl)methoxy]-tropane (AHN
      1055), incorporating probes of its stimulant and incentive/motivational effects
      and of its ability to influence cocaine self-administration. METHODS: We used
      open field activity and drug self-administration assays. To examine the effects
      of AHN-1055 on locomotor behavior, the analog was administered alone (0, 1, 3,
      and 10 mg/kg intraperitoneally) and in combination with cocaine (15 mg/kg i.p.).
      The influence of AHN-1055 on cocaine's intake was studied by administering the
      analog (0, 3, and 10 mg/kg i.p.) before the start of the self-administration
      sessions. To compare the addictive-like properties of AHN-1055 and cocaine,
      progressive ratio performance and abstinence-induced context-conditioned relapse
      were evaluated. RESULTS: AHN-1055 evoked robust and sustained locomotor activity
      when administered alone and increased cocaine-induced locomotor stimulation.
      Notably, the analog showed by comparison to cocaine weak reinforcing efficacy in
      a modified progressive ratio schedule of drug reinforcement, and contrary to
      cocaine, it showed no ability to promote context-conditioned relapse to drug
      seeking following stable self-administration and abstinence. Further, AHN-1055
      treatment blocked cocaine intake dose-dependently in rats with a steady history
      of cocaine self-administration without reducing responding for sucrose, a natural
      reward. CONCLUSIONS: These findings demonstrate essential psychopharmacological
      differences between AHN-1055 and cocaine and highlight important properties of
      the analog as a possible pharmacotherapy in cocaine addiction.

PMID- 19756526
TI  - Therapeutic potential of nicotine for methamphetamine-induced impairment of
      sensorimotor gating: involvement of pallidotegmental neurons.
AB  - INTRODUCTION: We have previously found that a disruption to prepulse inhibiton
      (PPI) induced by methamphetamine (METH) is associated with impaired functioning
      of pallidotegmental neurons, which play a crucial role in PPI of the startle
      reflex, through the activation of gamma-aminobutyric acid type B receptors in
      pedunculopontine tegmental neurons in mice. OBJECTIVES: Here, we examined the
      effect of nicotine on METH-induced impairment of PPI of the startle reflex
      focusing on dysfunctional pallidotegmental neurons and the neural system.
      RESULTS: Nicotine (0.15-0.5 mg/kg) ameliorated the deficit in PPI induced by
      acute METH, and the ameliorating effect of nicotine was antagonized by nicotinic
      receptor antagonists such as methyllycaconitine and dihydro-beta-erythroidine.
      The acute METH-induced disruption of PPI was accompanied by suppression of c-Fos
      expression in the lateral globus pallidus (LGP) as well as its induction in the
      caudal pontine reticular nucleus (PnC) in mice subjected to the PPI test.
      Nicotine-induced amelioration of PPI deficits in METH-treated mice was
      accompanied by a reversal of the changes in c-Fos expression in both the LGP and
      PnC to the basal level. CONCLUSIONS: Nicotine is effective in ameliorating the
      impairment of PPI caused by METH, which may be associated with normalization of
      the pallidotegmental neurons.

PMID- 19756527
TI  - Differential effects of escitalopram on attention: a placebo-controlled, double
      blind cross-over study.
AB  - RATIONALE: The role of serotonin (5-HT) in attention is not fully understood yet.
      OBJECTIVE: We aimed to investigate whether attention is modulated after treatment
      with escitalopram, a selective serotonin reuptake inhibitor (SSRI). METHODS: We
      administered 10 mg of escitalopram to 20 healthy subjects in a placebo
      controlled, double-blind cross-over design for 1 day or to another 20
      participants for a period of 7 days. Attention was assessed at time of plasma
      peak escitalopram concentration using the computerised Attention Network Test
      (ANT), which is a combined flanker and cued reaction time task. RESULTS: The
      results showed differential effects of serotonergic manipulation on attention
      depending on sequence of intake. For the acute treatment, we found significant
      differences between escitalopram and placebo for all warning conditions dependent
      of sequence of intake: participants receiving escitalopram as first treatment
      showed significant slower reaction times in all warning conditions as compared
      with placebo while participants receiving escitalopram as second treatment showed
      significant faster reaction times as compared with placebo. For the sub-chronic
      treatment, we found significant differences between escitalopram and placebo
      depending on sequence of intake, but only for the flanker condition: participants
      receiving escitalopram first had significant slower reaction times in incongruent
      trials with escitalopram as compared with placebo while participants starting
      with placebo had significant shorter reaction times in incongruent trials with
      escitalopram. CONCLUSIONS: Thus, the results showed a differential effect of
      escitalopram in cognition, especially in attention, and are discussed with regard
      to an interaction between serotonin and familiarity with the attention test.

PMID- 19756528
TI  - Effects of dimethylaminoethanol pyroglutamate (DMAE p-Glu) against memory
      deficits induced by scopolamine: evidence from preclinical and clinical studies.
AB  - RATIONALE: Dimethylaminoethanol pyroglutamate (DMAE p-Glu) is a compound
      resulting from the reaction between dimethylaminoethanol (an indirect precursor
      of acetylcholine) and pyroglutamic acid (a cyclic derivative of glutamic acid
      having procholinergic properties and promnesic effects in both animals and man).
      OBJECTIVES: The present study undertook preclinical and clinical evaluations to
      test a potential therapeutic utility for DMAE p-Glu in cognitive impairments
      related to central cholinergic deficit. MATERIALS AND METHODS: In preclinical
      study, DMAE p-Glu was studied in rats by intracerebral microdialysis in conscious
      freely moving animals, on performance of rats in the Morris water maze test of
      spatial memory, and on the deficit in passive avoidance behavior induced by
      scopolamine. The clinical study examined the effect of DMAE p-Glu on cognitive
      deficits induced by an intravenous injection of scopolamine in healthy young male
      subjects. RESULTS: In rat experiments, DMAE p-Glu increased the extracellular
      levels of choline and acetylcholine in the medial prefrontal cortex, as assessed
      by intracerebral microdialysis, improved performance in a test of spatial memory,
      and reduced scopolamine-induced memory deficit in passive avoidance behavior.
      Clinical study results show that scopolamine induced a memory deficit and that
      DMAE p-Glu produced a significant positive effect on scores in the Buschke test,
      as well as a slight but significant difference on choice reaction time.
      CONCLUSION: These results indicate that DMAE p-Glu reduces the deleterious effect
      of scopolamine on long-term memory in healthy volunteers and suggest that DMAE p
      Glu might be effective in reducing memory deficits in patients with cognitive
      impairment.

PMID- 19756529
TI  - Facilitation of intravenous nicotine self-administration in rats by a
      motivationally neutral sensory stimulus.
AB  - RATIONALE AND OBJECTIVE: Intravenous infusions of nicotine appear to exert little
      primary reinforcing effects in adult rats but, instead, maintain self
      administration behavior at least, in part, by increasing the intrinsic
      reinforcing effects of drug-paired sensory stimuli. The present study examined
      instead the impact of a motivationally neutral cue on self-administration.
      METHODS: Adult male Long-Evans rats were permitted to self-administer nicotine
      (0.015 mg/kg IV given over 30 s, 2 h/day) or saline presented with or without a
      sensory stimulus (light, white noise). Fixed and progressive ratio reinforcement
      schedules of nicotine reinforcement were tested. Experiment 2 determined whether
      noncontingent nicotine or mecamylamine (nicotinic antagonist) would induce lever
      pressing for either sensory stimulus. Experiment 3 tested whether the white noise
      stimulus alone could maintain responding after repeated pairing with self
      administered nicotine. Finally, the sensory stimuli were assessed for possible
      aversive properties. RESULTS: Nicotine infusions alone were at best weakly
      reinforcing. The white noise stimulus, presented alone, was neither reinforcing
      nor aversive, whereas the white light appeared marginally reinforcing. Both
      stimuli, however, facilitated intravenous nicotine self-administration. Neither
      nicotine nor mecamylamine challenge rendered the white noise reinforcing. The
      white noise, after being self-administered with nicotine, failed to maintain self
      administration behavior on its own. CONCLUSIONS: Even a motivationally neutral
      sensory stimulus, lacking detectable primary or secondary reinforcing properties,
      can facilitate self-administration of nicotine. Possibly, drug-paired stimuli
      provide a "response marker" or serve as a temporal bridge between the operant
      response and drug effect. Motivationally neutral stimuli may therefore serve to
      isolate primary reinforcing effects of nicotine.

PMID- 19756530
TI  - Alcohol-induced increases in smoking behavior for nicotinized and denicotinized
      cigarettes in men and women.
AB  - INTRODUCTION: Alcohol has been shown to increase smoking urges and smoking
      behavior. However, alcohol's effects on specific components of smoking behavior
      for nicotine versus non-nicotine factors and potential sex differences in this
      response have not been investigated. METHODS: Forty-two young male and female non
      dependent, heavy social drinking smokers participated in two double-blind
      laboratory sessions. They were randomized to either an alcohol (0.8 g/kg; n = 29)
      or placebo (n = 13) beverage pre-administration group. After beverage
      consumption, they were assessed for smoking urges and then given the opportunity
      to smoke cigarettes which were either all nicotinized (0.6 mg/cigarette) or
      denicotinized (< or =0.05 mg/cigarette) over a 3-h period; smoking behavior was
      quantified by a smoking topography device. Subjects took standardized puffs of
      the session's cigarette both before and after beverage administration to provide
      a reference when making future smoking choices. RESULTS: Alcohol, compared with
      placebo beverage, increased both men's and women's smoking urge, as well as
      subjective ratings of smoking reference puffs for either nicotinized or
      denicotinized cigarettes. In terms of smoking choice behavior, regardless of
      cigarette type, alcohol (>placebo) increased men's smoking behavior, including
      puff count, volume, and duration. In contrast, for women, smoking topography
      measures did not differ between alcohol and placebo conditions. DISCUSSION: In
      summary regardless of nicotine content, in men, alcohol increased smoking urge
      and behavior, whereas in women, alcohol increased smoking urge but did not
      increase smoking behavior. These results indicate that the mechanisms underlying
      co-use of alcohol and tobacco in women may be more complex than in men.

PMID- 19756531
TI  - Myosin-catalyzed ATP hydrolysis elucidated by 31P NMR kinetic studies and 1H PFG
      diffusion measurements.
AB  - We conducted (31)P NMR kinetic studies and (1)H-diffusion measurements on myosin
      catalyzed hydrolysis of adenosine triphosphate (ATP) under varied conditions. The
      data elucidate well the overall hydrolysis rate and various factors that
      significantly impact the reaction. We found that the enzymatic hydrolysis of ATP
      to adenosine diphosphate (ADP) was followed by ADP hydrolysis, and different
      nucleotides such as ADP and guanosine triphosphate acted as competitors of ATP.
      Increasing ATP or Mg(2+) concentration resulted in decreased hydrolysis rate, and
      such effect can be related to the decrease of ATP diffusion constants. Below 50
      degrees C, the hydrolysis was accelerated by increasing temperature following the
      Arrhenius' law, but the hydrolysis rate was significantly lowered at higher
      temperature (approximately 60 degrees C), due to the thermal-denaturation of
      myosin. The optimal pH range was around pH 6-8. These results are important for
      characterization of myosin-catalyzed ATP hydrolysis, and the method is also
      applicable to other enzymatic nucleotide reactions.

PMID- 19756532
TI  - Electrophoretic properties of BSA-coated quantum dots.
AB  - Low toxic InP/ZnS quantum dots (QDs), ZnS:Mn(2+)/ZnS nanocrystals and CdSe/ZnS
      nanoparticles were rendered water-dispersible by different ligand-exchange
      methods. Eventually, they were coated with bovine serum albumin (BSA) as a model
      protein. All particles were characterised by isotachophoresis (ITP), laser
      Doppler velocimetry (LDV) and agarose gel electrophoresis. It was found that the
      electrophoretic mobility and colloidal stability of ZnS:Mn(2+)/ZnS and CdSe/ZnS
      nanoparticles, which bore short-chain surface ligands, was primarily governed by
      charges on the nanoparticles, whereas InP/ZnS nanocrystals were not charged per
      se. BSA-coated nanoparticles showed lower electrophoretic mobility, which was
      attributed to their larger size and smaller overall charge. However, these
      particles were colloidally stable. This stability was probably caused by steric
      stabilisation of the BSA coating.

PMID- 19756533
TI  - Nanomaterial characterization: considerations and needs for hazard assessment and
      safety evaluation.
AB  - Nanotechnology is a rapidly emerging field of great interest and promise. As new
      materials are developed and commercialized, hazard information also needs to be
      generated to reassure regulators, workers, and consumers that these materials can
      be used safely. The biological properties of nanomaterials are closely tied to
      the physical characteristics, including size, shape, dissolution rate,
      agglomeration state, and surface chemistry, to name a few. Furthermore, these
      properties can be altered by the medium used to suspend or disperse these water
      insoluble particles. However, the current toxicology literature lacks much of the
      characterization information that allows toxicologists and regulators to develop
      "rules of thumb" that could be used to assess potential hazards. To effectively
      develop these rules, toxicologists need to know the characteristics of the
      particle that interacts with the biological system. This void leaves the
      scientific community with no options other than to evaluate all materials for all
      potential hazards. Lack of characterization could also lead to different
      laboratories reporting discordant results on seemingly the same test material
      because of subtle differences in the particle or differences in the dispersion
      medium used that resulted in altered properties and toxicity of the particle. For
      these reasons, good characterization using a minimal characterization data set
      should accompany and be required of all scientific publications on nanomaterials.

PMID- 19756534
TI  - Bag-SPE--a convenient extraction method for screening of pharmaceutical residues
      in influent and effluent water from sewage treatment plants.
AB  - Bag-SPE is a solid-phase extraction (SPE) technique here applied to sample
      pharmaceutical residues in wastewater. The device, consisting of 20 mg
      polystyrene-divinylbenzene (PS-DVB) enclosed in a woven polyester fabric was
      immersed into a 20-mL sample. Extraction of the analytes was performed under
      gentle rotation (25 rpm) until distribution equilibrium was achieved (4 h). The
      extraction efficiency for thirteen pharmaceuticals was evaluated for the bag-SPE
      sampler compared to a conventional SPE cartridge (Oasis HLB). All analyses were
      determined on an ultra-performance liquid chromatography (UPLC) coupled to a
      quadrupole time-of-flight (QToF) mass spectrometer. The detection limit of the
      bag-SPE technique for the analytes in wastewater ranged from 15-100 ng/L with
      recoveries between 20.7% and 58.2% and ion suppressions between 2.2% and 53.2%.
      Although the extraction efficiencies were lower with the bag-SPE sampler compared
      to the SPE technique, the two methods showed similar detection limits due to the
      lower ion suppression experienced with the bag-SPE. The results demonstrate that
      bag-SPE is an attractive alternative to the more, in terms of manual handling,
      demanding SPE technique.

PMID- 19756535
TI  - Electrochemical reduction of the iodinated contrast medium iomeprol: iodine mass
      balance and identification of transformation products.
AB  - Potentiostatic-controlled electrochemical reduction of iomeprol was used to
      deiodinate iomeprol (IMP), a representative of the iodinated X-ray contrast
      media. The reduction process was followed by product analysis with liquid
      chromatography-electrospray ionization-tandem mass spectrometry and ion
      chromatography-inductively coupled plasma-mass spectrometry. The identification
      is mainly based on the interpretation of the mass fragmentation. The product
      analysis showed a rather selective deiodination process with the successive
      occurrence of IMP-I, IMP-2I, IMP-3I, and a transformation product (TP),
      respectively. The TP was formed from IMP-3I by a further cleavage of an amide
      bond and release of a (C=O)CHOH group from the side chain of IMP. The iodine mass
      balance on the basis of IMP and iodide showed a gap of about 26% at the beginning
      of the electrolysis process which could be completely closed by taking the
      intermediates IMP-I and IMP-2I into consideration. This means that the major
      intermediates and the TPs were considered and that the reduction process is a
      rather selective one to remove organically bound iodine from X-ray contrast
      media. An attractive application area would be the electrochemical deiodination
      of X-ray contrast media in urine of patients or hospital effluents.

PMID- 19756536
TI  - Determination of melamine in animal feed based on liquid chromatography tandem
      mass spectrometry analysis and dynamic microwave-assisted extraction coupled on
      line with strong cation-exchange resin clean-up.
AB  - In this work, a new method was developed for the determination of melamine (MEL)
      in animal feed. The method was based on the on-line coupling of dynamic microwave
      assisted extraction (DMAE) to strong cation-exchange (SCX) resin clean-up. The
      MEL was first extracted by 90% acidified methanol aqueous solution (v/v, pH = 3)
      under the action of microwave energy, and then the extract was cooled and passed
      through the SCX resin. Thus, the protonated MEL was retained on the resin through
      ion exchange interaction and the sample matrixes were washed out. Some obvious
      benefits were achieved, such as acceleration of analytical process, together with
      reduction in manual handling, risk of contamination, loss of analyte, and sample
      consumption. Finally, the analyte was separated by a liquid chromatograph with a
      SCX analytical column, and then identified and quantitatived by a tandem mass
      spectrometry with positive ionization mode and multiple-reaction monitoring. The
      DMAE parameters were optimized by the Box-Behnken design. The linearity of
      quantification obtained by analyzing matrix-matched standards is in the range of
      50-5,000 ng g(-1). The limit of detection and limit of quantification obtained
      are 12.3 and 41.0 ng g(-1), respectively. The mean intra- and inter-day
      precisions expressed as relative standard deviations with three fortified levels
      (50, 250, and 500 ng g(-1)) are 5.1% and 7.3%, respectively, and the recoveries
      of MEL are in the range of 76.1-93.5%. The proposed method was successfully
      applied to determine MEL in different animal feeds obtained from the local
      market. MEL was detectable with the contents of 279, 136, and 742 ng g(-1) in
      three samples.

PMID- 19756537
TI  - Chemometric tools for identification of volatile aroma-active compounds in
      oregano.
AB  - One of the purposes of chemical analysis is to find quick and efficient methods
      to answer complex analytical questions in the life sciences. New analytical
      methods, in particular, produce a flood of data which are often very badly
      arranged. An effective way to overcome this problem is to apply chemometric
      methods. As part of the following investigations, three brands of oregano were
      analysed to identify their volatile aroma-active compounds. Two techniques were
      applied--gas chromatograpy-olfactometry (GC-O) and human sensory evaluation.
      Aroma-impact compounds could be identified in the main brands of oregano with the
      aid of chemometric methods (principal-components analysis, hierarchical cluster
      analysis, linear discriminant analysis, partial least-squares regression).
      Therefore, it is possible to reduce the analysis of sensory and olfactometry to
      relevant attributes. This makes classifying new species easier, much faster, and
      less expensive and is the premise for quick and more economic identification of
      new potential genotypes for oregano plant breeding. A comprehensive list of
      oregano key odourants, determined by GC-O and human sensory evaluation using
      different methods of supervised and unsupervised pattern cognition, has not
      previously been published.

PMID- 19756538
TI  - A reference-gene-based quantitative PCR method as a tool to determine Fusarium
      resistance in wheat.
AB  - In recent years, plant breeders made great progress in breeding Fusarium-tolerant
      wheat lines. However, total resistance to this genus of plant pathogenic fungi
      has not yet been achieved as the resistance genes are located on several distinct
      genetic regions. Visual scoring of disease symptoms in combination with the
      analysis of mycotoxins is commonly applied to assess the tolerance of new lines.
      Both approaches are indirect methods and do not mandatorily determine the
      accumulated fungal biomass. Quantitative PCR is a useful tool to assess fungal
      biomass based on the abundance of organism-specific DNA. The aim of this study
      was the development of a quantitative PCR assay for trichothecene-producing
      Fusarium species and to adapt this method for resistance assessment of wheat
      lines artificially infected with Fusarium graminearum and Fusarium culmorum.
      Several DNA-extraction methods for wheat samples were evaluated and optimized for
      downstream real-time PCR analysis and furthermore, a new reference-gene-based
      approach for more accurate quantification of Fusarium biomass in cereals is
      presented. The co-determination of a plant gene was used to compensate for
      unequal DNA-extraction efficiencies.

PMID- 19756539
TI  - A rapid lateral flow test for the determination of total type B fumonisins in
      maize.
AB  - A one-step lateral flow test was developed for the quantitative determination of
      total type B fumonisins in maize with a test range up to 4,000 microg/kg and a
      limit of detection of 199 microg/kg. The test presented gives a result within 4
      min, including 1 min strip drying, and does not require any sample cleanup steps
      after a previous 3-min sample extraction. Quantitative readout with a compact
      photometric strip reader will also indicate the best suited measurement range
      when needed. The test is based on a competitive immunoassay format where a ready
      to-use antibody-colloidal gold particle complex is mixed with 50 microL sample
      extract in a microwell and used as a signal reagent. The test strip is inserted
      into the well and the mixed content migrates onto the strip, which contains a
      test zone and a control zone. Mycotoxin-protein conjugate coated on the test zone
      captures free signal reagent, and colored particles concentrate, forming a
      visible line. The intensity of the test line is dependent on the total fumonisin
      concentration in the sample. Naturally contaminated quality-control maize
      material was used for matrix-matched calibration of photometric readout. The test
      presented is both quantitative and rapid, with no cross-reactivity to other
      mycotoxins. The applicability of the lateral flow test was shown by the screening
      of 23 naturally contaminated maize samples. Relative standard deviations ranged
      from 1.7 to 32.9%.

PMID- 19756540
TI  - Review of secondary metabolites and mycotoxins from the Aspergillus niger group.
AB  - Filamentous fungi in the Aspergillus section Nigri (the black aspergilli)
      represent some of the most widespread food and feed contaminants known but they
      are also some of the most important workhorses used by the biotechnological
      industry. The Nigri section consists of six commonly found species (excluding A.
      aculeatus and its close relatives) from which currently 145 different secondary
      metabolites have been isolated and/or detected. From a human and animal safety
      point of view, the mycotoxins ochratoxin A (from A. carbonarius and less
      frequently A. niger) and fumonisin B(2) (from A. niger) are currently the most
      problematic compounds. Especially in foods and feeds such as coffee, nuts, dried
      fruits, and grape-based products where fumonisin-producing fusaria are not a
      problem, fumonisins pose a risk. Moreover, compounds such as malformins, naptho
      gamma-pyrones, and bicoumarins (kotanins) call for monitoring in food, feed, and
      biotechnology products as well as for a better toxicological evaluation, since
      they are often produced in large amounts by the black aspergilli. For chemical
      differentiation/identification of the less toxic species the diketopiperazine
      asperazine can be used as a positive marker since it is consistently produced by
      A. tubingensis (177 of 177 strains tested) and A. acidus (47 of 47 strains
      tested) but never by A. niger (140 strains tested). Naptho-gamma-pyrones are the
      compounds produced in the highest quantities and are produced by all six common
      species in the group (A. niger 134 of 140; A. tubingensis 169 of 177; A. acidus
      44 of 47; A. carbonarius 40 of 40, A. brasiliensis 18 of 18; and A. ibericus
      three of three).

PMID- 19756541
TI  - Dispersive liquid-liquid microextraction using an in situ metathesis reaction to
      form an ionic liquid extraction phase for the preconcentration of aromatic
      compounds from water.
AB  - A novel microextraction method is introduced based on dispersive liquid-liquid
      microextraction (DLLME) in which an in situ metathesis reaction forms a water
      immiscible ionic liquid (IL) that preconcentrates aromatic compounds from water
      followed by separation using high-performance liquid chromatography. The
      simultaneous extraction and metathesis reaction forming the IL-based extraction
      phase greatly decreases the extraction time as well as provides higher enrichment
      factors compared to traditional IL DLLME and direct immersion single-drop
      microextraction methods. The effects of various experimental parameters including
      type of extraction solvent, extraction and centrifugation times, volume of the
      sample solution, extraction IL and exchanging reagent, and addition of organic
      solvent and salt were investigated and optimized for the extraction of 13
      aromatic compounds. The limits of detection for seven polycyclic aromatic
      hydrocarbons varied from 0.02 to 0.3 microg L(-1). The method reproducibility
      produced relative standard deviation values ranging from 3.7% to 6.9%. Four real
      water samples including tap water, well water, creek water, and river water were
      analyzed and yielded recoveries ranging from 84% to 115%.

PMID- 19756542
TI  - Solution to quality assurance challenge 8.

PMID- 19756543
TI  - Development of a voltammetric electronic tongue for discrimination of edible
      oils.
AB  - In this paper, we propose a novel strategy to perform cyclic voltammetric
      measurements with a platinum microelectrode directly in edible oil samples. The
      microelectrode was employed as an electronic tongue that, along with the
      application of chemometrics to the current-potential responses, proved useful for
      discriminating oils on the basis of their quality and geographical origin. The
      method proposed here is based on the use of suitable room temperature ionic
      liquids, added to oils as supporting electrolytes to provide conductivity to the
      low-polarity samples. The entire voltammograms, recorded directly on the oil/RTIL
      mixtures, were processed via principal component analysis and a classification
      technique (K nearest neighbors), to extract information on samples
      characteristics. Data processing showed that oils having different nature (i.e.
      maize and olive) or geographical origin (i.e. olive oils coming from different
      regions) can be distinguished.

PMID- 19756544
TI  - Evaluation of different calibration strategies for the analysis of pure copper
      and zinc samples using femtosecond laser ablation ICP-MS.
AB  - Solution-doped metal powder pellets as well as aspirated liquids were used as
      calibration samples to analyze pure copper and zinc certified reference materials
      (CRMs) by femtosecond laser ablation ICP-MS. It was demonstrated that calibration
      by copper pellets resulted in relative deviations up to 20%, whereas fs-LA-ICP-MS
      among copper-based CRMs led to inaccuracies in the same range unless nominal mass
      fractions were chosen to be <3 mg/kg. Calibration by zinc pellets generally
      provided better accuracy. Depending on the analyte considered, deviations below
      10% were obtained even for mass fractions close to the limit of quantification.
      Our data, therefore, indicate solution-doped metal powder pellets to be suitable
      as calibration samples for fs-LA-ICP-MS of metals. Furthermore, the utilization
      of liquid standards for calibration was found to result in stronger deviations of
      up to 50% for both copper and zinc samples which, in addition, turned out to be
      dependent on the plasma conditions.

PMID- 19756545
TI  - The study of bronze statuettes with the help of neutron-imaging techniques.
AB  - Until recently fabrication techniques of Renaissance bronzes have been studied
      only with the naked eye, microscopically, videoscopically and with X-radiography.
      These techniques provide information on production techniques, yet much important
      detail remains unclear. As part of an interdisciplinary study of Renaissance
      bronzes undertaken by the Rijksmuseum Amsterdam, neutron-imaging techniques have
      been applied with the aim of obtaining a better understanding of bronze
      workmanship during the Renaissance period. Therefore, an explanation of the
      fabrication techniques is given to better understand the data collected by these
      neutron-imaging techniques. The data was used for tomography studies, which
      reveal hidden aspects that could not at all or scarcely be seen using X
      radiography. For this specific study, the representative bronze 'Hercules
      Pomarius' of Willem van Tetrode (ca 1520-1588) has been examined, along with 20
      other Renaissance bronzes from the Rijksmuseum collection.

PMID- 19756546
TI  - The size distribution of 'gold standard' nanoparticles.
AB  - The spherical gold nanoparticle reference materials RM 8011, RM 8012, and RM
      8013, with a nominal radius of 5, 15, and 30 nm, respectively, have been
      available since 2008 from NIST. These materials are recommended as standards for
      nanoparticle size measurements and for the study of the biological effects of
      nanoparticles, e.g., in pre-clinical biomedical research. We report on
      determination of the size distributions of these gold nanoparticles using
      different small-angle X-ray scattering (SAXS) instruments. Measurements with a
      classical Kratky type SAXS instrument are compared with a synchrotron SAXS
      technique. Samples were investigated in situ, positioned in capillaries and in
      levitated droplets. The number-weighted size distributions were determined
      applying model scattering functions based on (a) Gaussian, (b) log-normal, and
      (c) Schulz distributions. The mean radii are 4.36 +/- 0.04 nm (RM 8011), 12.20 +/
      0.03 nm (RM 8012), and 25.74 +/- 0.27 nm (RM 8013). Low polydispersities,
      defined as relative width of the distributions, were detected with values of
      0.067 +/- 0.006 (RM 8011), 0.103 +/- 0.003, (RM 8012), and 0.10 +/- 0.01 (RM
      8013). The results are in agreement with integral values determined from
      classical evaluation procedures, such as the radius of gyration (Guinier) and
      particle volume (Kratky). No indications of particle aggregation and particle
      interactions--repulsive or attractive--were found. We recommend SAXS as a
      standard method for a fast and precise determination of size distributions of
      nanoparticles.

PMID- 19756547
TI  - Direct injection horse urine analysis for the quantification and identification
      of threshold substances for doping control. III. Determination of salicylic acid
      by liquid chromatography/quadrupole time-of-flight mass spectrometry.
AB  - In equine sport, salicylic acid is prohibited with a threshold level of 750
      microg mL(-1) in urine; hence, doping control laboratories have to establish
      quantitative and qualitative methods for its determination. A simple and rapid
      liquid chromatographic/mass spectrometric method was developed and validated for
      the quantification and identification of salicylic acid. Urine samples after 900
      fold dilution and addition of the internal standard (4-methylsalicylic acid) were
      directly injected to the liquid chromatography/quadrupole time-of-flight mass
      spectrometry system. Electrospray ionization in negative mode with full scan
      acquisition mode and product ion scan mode were chosen for the quantification and
      identification of salicylic acid, respectively. Run time was 2.0 min. The tested
      linear range was 2.5-50 microg mL(-1) (after 100-fold sample dilution). The
      relative standard deviations of intra- and inter-assay analysis of salicylic acid
      in horse urine were lower than 2.5% and 2.8%, respectively. Overall accuracy
      (relative percentage error) was less than 3.3%. Method was applied to two real
      samples found to be positive for salicylic acid, demonstrating simplicity,
      accuracy, and selectivity.

PMID- 19756548
TI  - Rapid, sensitive and simultaneous determination of fluorescence-labeled
      designated substances controlled by the Pharmaceutical Affairs Law in Japan by
      ultra-performance liquid chromatography coupled with electrospray-ionization time
      of-flight mass spectrometry.
AB  - A simultaneous determination method based on ultra-performance liquid
      chromatography (UPLC) with fluorescence (FL) detection and electrospray
      ionization time-of-flight mass spectrometry (ESI-TOF-MS) was developed for 16
      "designated substances" (Shitei-Yakubutsu) controlled by the Pharmaceutical
      Affairs Law in Japan. These substances were first labeled with 4-(N,N
      dimethylaminosulfonyl)-7-fluoro-2,1,3-benzoxadiazole at 60 degrees C for 2 h in
      0.1 M borax (pH 9.3). The resulting fluorophores were well separated by reversed
      phase chromatography using an Acquity UPLC BEH C(18) column (1.7 microm, 100 mm x
      2.1 mm i.d.) by isocratic elution with a mixture of water and acetonitrile
      methanol (20:80) containing 0.1% formic acid. The separated derivatives were
      sensitively detected by both FL and TOF-MS. However, the determination of several
      designated substances by FL detection showed interference from endogenous
      substances in biological samples. Therefore, the determination in real samples
      was carried out by a combination of UPLC separation and ESI-TOF-MS detection. The
      structures of the designated substances were identified from the protonated
      molecular ions [M+H](+) obtained from the TOF-MS measurement. The calibration
      curves obtained from the peak area ratios of the internal standard (I.S.), i.e.,
      3-phenyl-1-propylamine, and the designated substances versus the injection
      amounts showed good linearity. The limits of detection (S/N = 3) and the limits
      of quantification (S/N = 10) in 0.1 mL of human plasma and urine for the present
      method were 0.30-150 pmol and 1.0-500 pmol, respectively. Good accuracy and
      precision (according to intraday and interday assays) were also obtained with the
      present procedure. This method was applied to analyses of human plasma, urine and
      real products.

PMID- 19756549
TI  - Rapid induction of the immediate early gene c-fos in a chick forebrain system
      involved in memory.
AB  - Previous work has shown that expression of Fos protein in neurons of the
      intermediate and medial mesopallium (IMM), a memory region in the forebrain of
      the domestic chick, increases in a learning-related manner after behavioural
      imprinting. We show here, using in situ hybridisation, that when chicks are
      trained for 15 min with an imprinting stimulus, expression of c-fos mRNA in the
      IMM rises to a maximum at or before the end of this training period. The results
      suggest that the learning-related increase in Fos protein production, which
      occurs in identifiable neuronal sub-populations in the IMM, reflects events that
      make an early contribution to learning and/or memory processing.

PMID- 19756550
TI  - Head stability during quiet sitting in children with cerebral palsy: effect of
      vision and trunk support.
AB  - Deficits in postural control are one of the hallmarks of disability in children
      with cerebral palsy (CP). Yet, much remains unknown regarding the etiology of
      postural deficits in these children. Here we evaluated postural control at a
      simplified task level by measuring head stability during quiet sitting while
      systematically manipulating the level of trunk support and vision in 15 children
      with CP (6-16 years), 26 typically developing (TD) children (4-14 years), and 11
      adults. While TD children did not differ significantly from adults, children with
      CP had greater head movement than adults in both the sagittal and frontal planes
      under all conditions except frontal plane movement with Torso Support. Vision did
      not affect head stability in the sagittal plane for any group while it had
      differential effects on head stability in the frontal plane. Lack of vision
      improved head stability in adults and older TD children while destabilizing the
      head in young children (TD and CP) during the most unstable sitting position.
      Moreover, vision affected children with CP differently depending on their
      movement disorder. Children with spastic CP performed worse with eyes closed
      while those with dyskinetic CP had improved head stability with eyes closed. Our
      results demonstrate that children with mild to moderate CP have deficits in head
      stability even during quiet sitting.

PMID- 19756551
TI  - Overlapping functional anatomy for working memory  and visual search.
AB  - Recent behavioural findings using dual-task paradigms demonstrate the importance
      of both spatial and non-spatial working memory processes in inefficient visual
      search (Anderson et al. in Exp Psychol 55:301-312, 2008). Here, using functional
      magnetic resonance imaging (fMRI), we sought to determine whether brain areas
      recruited during visual search are also involved in working memory. Using
      visually matched spatial and non-spatial working memory tasks, we confirmed
      previous behavioural findings that show significant dual-task interference
      effects occur when inefficient visual search is performed concurrently with
      either working memory task. Furthermore, we find considerable overlap in the
      cortical network activated by inefficient search and both working memory tasks.
      Our findings suggest that the interference effects observed behaviourally may
      have arisen from competition for cortical processes subserved by these
      overlapping regions. Drawing on previous findings (Anderson et al. in Exp Brain
      Res 180:289-302, 2007), we propose that the most likely anatomical locus for
      these interference effects is the inferior and middle frontal cortex of the right
      hemisphere. These areas are associated with attentional selection from memory as
      well as manipulation of information in memory, and we propose that the visual
      search and working memory tasks used here compete for common processing resources
      underlying these mechanisms.

PMID- 19756552
TI  - Practice-related improvements in posture control differ between   young and older
      adults exposed to continuous, variable amplitude   oscillations of the support
      surface.
AB  - Healthy older adults were repeatedly exposed to continuous, variable amplitude
      oscillations of the support surface to determine (1) whether age affects the
      capacity for postural motor learning under continuous perturbation conditions
      with limited predictability and (2) whether practice leads to modifications in
      the control strategy used to maintain balance in older adults. During training, a
      translating platform underwent 45-s trials of constant frequency (0.5 Hz) and
      seemingly random amplitude oscillations (range +?- 2 to 15 cm). The middle 15 s
      of each trial contained the same sequence of oscillation amplitudes. This
      repeated middle segment was the same as the repeated segment used in Van Ooteghem
      et al. (Exp Brain Res 187(4): 603-611, 2008) and was therefore used for analyses.
      To examine learning, participants performed a retention test following a 24-h
      delay. Kinematic data were used to derive spatial and temporal measures of whole
      body centre of mass (COM), trunk, thigh, and shank segment orientation, and ankle
      and knee angle from performance during the repeated middle segment. Results
      showed that with training, older adults maintained the capacity to learn adaptive
      postural responses in the form of improved temporal control of the COM and
      minimization of trunk instability a a rate comparable to young adults. With
      practice, however older adults maintained a more rigid, 'platform-fixed' control
      strategy which differed from young adults who shifted towards 'gravity-fixed'
      control and decreased COM motion. This study provides important insight into the
      ability of older adults to demonstrate longer-term improvements in postural
      regulation.

PMID- 19756553
TI  - Receptive field plasticity of area 17 visual cortical neurons of adult rats.
AB  - In contrast to somatosensory cortex (SI), where the pervasiveness of
      reorganizational capacities is well-established, plasticity of receptive fields
      (RFs) of adult primary visual cortex (VI) remains controversial. To investigate
      RF plasticity in VI of adult rats, we here used intracortical microstimulation
      (ICMS) to overcome particularities related to stimulus presentation and training
      procedures which limit comparison across modalities. Our results show that VI RFs
      can be altered by ICMS; however, changes depended on the pre-ICMS RF size.
      Initially small RFs expanded after 2 h of ICMS with little signs of recovery
      within the next hours, while initially large RFs remained unaffected. Inspection
      of the time course of neuron responses revealed, however, that in large RFs early
      response components were enhanced, while late response components were reduced
      resulting in changes of the spatiotemporal RF properties. Although plastic
      changes in VI showed a substantial heterogeneity, our results indicate a capacity
      of VI neurons to undergo plastic changes comparable to SI neurons. However, the
      magnitude and aspects of reversibility appeared to be different suggesting a
      significant modality-specificity of reorganizational changes of cortical sensory
      neurons.

PMID- 19756554
TI  - Haptic curvature contrast in raised lines and solid shapes.
AB  - It is known that our senses are influenced by contrast effects and aftereffects.
      For haptic perception, the curvature aftereffect has been studied in depth but
      little is known about curvature contrast. In this study we let observers explore
      two shapes simultaneously. The shape felt by the index finger could either be
      flat or convexly curved. The curvature at the thumb was varied to quantify the
      curvature of a subjectively flat shape. We found that when the index finger was
      presented with a convex shape, a flat shape at the thumb was also perceived to be
      convex.The effect is rather strong, on average 20% of the contrasting curvature.
      The contrast effect was present for both raised line stimuli and solid shapes.
      Movement measurements revealed that the curvature of the path taken by the
      metacarpus (part of the hand that connects the fingers) was approximately the
      average of the path curvatures taken by the thumb and index finger. A failure to
      correct for the movement of the hand could explain the contrast effect.

PMID- 19756555
TI  - Rhabdomyolysis associated with fibrate therapy: review of 76 published cases and
      a new case report.
AB  - PURPOSE: Fibrates are used to manage mixed dyslipidemia. However, these drugs
      have the potential risk of inducing rhabdomyolysis. This paper gives an overview
      of the literature on rhabdomyolysis associated with fibrate therapy. METHODS: We
      reported a case of rhabdomyolysis induced by fenofibrate and reviewed the
      published rhabdomyolysis cases associated with fibrate therapy. RESULTS: Seventy
      six published rhabdomyolysis cases associated with fibrates were evaluated, and a
      nondiabetic, nonhypertensive patient who presented with rhabdomyolysis caused by
      fenofibrate was reported. The onset time of the reaction varied between 36 h and
      6 months. Gemfibrozil was the most frequent agent associated with rhabdomyolysis,
      followed by bezafibrate, fenofibrate, ciprofibrate, and clofibrate. Twenty-three
      cases were associated with fibrate monotherapy and 54 with fibrate therapy
      combined with statins or other drugs potentially interacting with fibrates.
      Sixteen cases had chronic renal failure before fibrate therapy, and 6 had
      hypothyroidism. Fifty-four complicated acute renal failure. After discontinuation
      of the fibrates and hydration, most patients recovered. CONCLUSIONS: Chronic
      renal failure may be a risk factor for rhabdomyolysis associated with fibrates.
      Although rhabdomyolysis usually occurred when fibrates were combined with
      statins, a well-known class of agents that potentially induce rhabdomyolysis,
      precautions against serious adverse effects should also be taken with fibrate
      monotherapy.

PMID- 19756556
TI  - Drug utilisation on a preterm and neonatal intensive care unit in Germany: a
      prospective, cohort-based analysis.
AB  - PURPOSE: This study aims to describe the drug use on a Neonatal Intensive Care
      Unit (NICU) at a University Children's Hospital in Germany, to investigate the
      licensing status of the drugs used and to conclude critical areas in neonatal
      intensive care to support prioritisation of future research. METHODS: An 11
      month, prospective cohort study was conducted on the NICU at the University
      Children's Hospital Erlangen, Germany. All products prescribed during the study
      period were analysed whether or not the SPC contains information on term and
      preterm neonates. RESULTS: A total of 183 patients (102 male) with a mean
      gestational age of 33.6 weeks (minimum = 24, maximum = 42) were included. The
      mean length of hospitalisation was 19.4 days (minimum = 2, maximum = 167). On
      average, patients received 11.1 drugs (minimum = 0, maximum = 46). The majority
      of prescriptions were accounted for by antibiotics (n = 515), which were received
      by 90% of all patients, followed by CNS drugs (n = 448) and respiratory drugs (n
      = 306). Of all the different drugs prescribed (n = 102) only 38% had information
      regarding their use in patients aged less than 1 month in their SPC. Analgesics
      and cardiovascular drugs were prescribed frequently, but without having
      information for use in neonates. Seventy percent of all patients and 100% of very
      preterm infants received at least one of these drugs. CONCLUSIONS: Treatment
      strategies on a preterm intensive care unit are complex and little information is
      available for the drugs used. Analgesics and cardiovascular drugs are of major
      concern. Efforts will have to be made to conduct well-designed and powered
      studies in this vulnerable population.

PMID- 19756557
TI  - Population pharmacokinetic analysis of infliximab in patients with ulcerative
      colitis.
AB  - PURPOSE: Infliximab, a monoclonal antibody, is approved for the treatment of
      inflammatory diseases at doses that depend on the patient disease population. It
      was the aim of this study to evaluate its population pharmacokinetics in patients
      with moderately to severely active ulcerative colitis and characterize patient
      covariates that affect its disposition in this population. METHODS: Information
      collected from 482 patients in two randomized, double-blind, placebo-controlled
      international studies were analyzed using NONMEM. RESULTS: A two-compartment,
      population pharmacokinetic model described the serum infliximab concentration
      time data. Population pharmacokinetic estimates (typical value +/- standard
      error), based on the final covariate model, were clearance (CL: 0.407 +/- 0.0103
      L/day), apparent volumes of distribution in the central (V(1): 3.29 +/- 0.0679 L)
      and peripheral (V(2): 4.13 +/- 0.16 L) compartments, and intercompartment
      clearance (Q: 7.14 +/- 0.489 L/day). Infliximab exhibited interindividual
      variability for CL and V(1) of 37.7% and 22.1%, respectively. Infliximab t(1/2)
      is approximately 14 days. Covariate analysis showed that V(1) increased as body
      weight increased, and CL was higher in patients who developed antibodies to
      infliximab. An additional novel covariate, serum albumin concentration, was found
      to be inversely and strongly related to infliximab clearance in this population.
      CONCLUSIONS: The disposition of infliximab in patients with moderately to
      severely active ulcerative colitis, unlike in rheumatoid arthritis, was not
      affected by coadministration of immunomodulators and corticosteroids but was
      related to formation of antibodies to infliximab and, notably, to serum albumin
      levels.

PMID- 19756558
TI  - Eltrombopag, an oral thrombopoietin receptor agonist, has no impact on the
      pharmacokinetic profile of probe drugs for cytochrome P450 isoenzymes CYP3A4,
      CYP1A2, CYP2C9 and CYP2C19 in healthy men: a cocktail analysis.
AB  - PURPOSE: It is likely that the thrombopoietin receptor agonist eltrombopag will
      be administered concomitantly with other medications in the treatment of
      thrombocytopenia. Therefore the potential for eltrombopag to interact with
      cytochrome P450 activity was investigated. METHODS: Twenty-four healthy men
      received eltrombopag 75 mg/day on days 3-9, midazolam 5 mg (a probe for CYP3A4)
      on days 1 and 8 and a probe cocktail on days 2 and 9 that included caffeine 100
      mg (CYP1A2), flurbiprofen 50 mg (CYP2C9) and omeprazole 20 mg (CYP2C19). RESULTS:
      Midazolam pharmacokinetic parameters were comparable before and after eltrombopag
      administration; geometric least squares (GLS) mean ratio (90% confidence
      intervals, CI) area under the curve from zero to infinity (AUC(0-infinity)) was
      1.03 (0.94,1.12) and maximum plasma concentration (C(max)) was 0.98 (0.86,1.07).
      Metabolic indices for other CYP isozymes were also equivalent before and after
      eltrombopag. GLS mean ratio (90% CI) for the paraxanthine:caffeine concentration
      ratio at 8 h postdose was 0.97 (0.92,1.03), for conjugated + unconjugated and
      unconjugated 4-hydroxy-flurbiprofen recovery in urine over 0-8 h was 0.95
      (0.93,0.97) and 0.93 (0.88,0.98), respectively, and for the plasma omeprazole:5
      hydroxyomeprazole concentration ratio at 2- and 3-h postdose was 1.00 (0.93,1.08)
      and 1.02 (0.88,1.18), respectively. CONCLUSION: Once-daily administration of
      eltrombopag 75 mg for 7 days did not alter CYP3A4, CYP1A2, CYP2C9 or CYP2C19
      activity in healthy volunteers.

PMID- 19756559
TI  - Effects of CYP2C19 and CYP2C9 genotypes on pharmacokinetic variability of
      valproic acid in Chinese epileptic patients: nonlinear mixed-effect modeling.
AB  - PURPOSE: To evaluate the effects of CYP2C19 and CYP2C9 genotypes on the
      pharmacokinetic variability of valproic acid (VPA) in epileptic patients using a
      population pharmacokinetic (PPK) approach. METHODS: VPA concentrations were
      measured in 287 epileptic patients, who were genotyped for CYP2C19*2/*3 and
      CYP2C9*3. Patients who were on monotherapy with VPA were divided into two groups,
      a PPK-model group (n = 177) and a PPK-valid group (n = 110). The PPK parameter
      values for VPA were calculated in the PPK-model group by using the NONMEM
      software. Ultimately, a biological model and a final model were established. Each
      model was then used to independently predict the concentrations of the PPK-valid
      group to validate the two models. RESULTS: There was a significant effect of the
      CYP2C19 and CYP2C9 genotypes on the pharmacokinetic (PK) variability (P < 0.01)
      in the final PPK model of CL/F. The interindividual CL was calculated according
      to the final model: CL/F = 0.0951 x (1 + e(0.0267 x (3 - genotype))) + 0.0071 x
      age (L/h). The coefficient of variation (CV) (omega CL/F) of the final model was
      29.3%, while that of the biological model was 31.7%. Based on the genotype, the
      individual PK parameters can be calculated more accurately than before.
      CONCLUSION: The CYP2C19 and CYP2C9 genotypes significantly influenced the PK
      variability of VPA, as quantified by NONMEM software.

PMID- 19756560
TI  - Endovascular stent-assisted thrombolysis in acute occlusive carotid artery
      dissection.
AB  - INTRODUCTION: Internal carotid artery dissection with tandem internal carotid and
      middle cerebral artery occlusion may be responsible for large cerebral infarction
      that carries a general poor prognosis. Recanalization of internal carotid artery
      (ICA) dissection by stent-assisted thrombolysis has been recently proposed. We
      report two cases of acute symptomatic ICA dissection with tandem occlusion
      successfully treated with emergent endovascular stent-assisted thrombolysis using
      new self-expandable intracranial stents. METHODS: A 37-year-old woman and a 59
      year-old man were admitted in our hospital after acute severe symptoms of right
      hemispheric stroke with National Institutes of Health Stroke Scale (NIHSS) scores
      of 15 and 18, respectively. In both cases, magnetic resonance angiography showed
      tandem occlusion and angiography confirmed tandem occlusion with ICA dissection.
      An extensive mismatch region was diagnosed by Perfusion-diffusion MRI of the
      brain within 3 h after symptoms onset. Treatment was initiated 4 h after symptom
      onset by implantation of self-expandable intracranial stents into the dissected
      ICA and administration of intra-arterial recombinant tissue plasminogen
      activator. RESULTS: Recanalization of the ICA and middle cerebral artery (MCA)
      was accomplished within 6 h after symptoms onset. In both cases, no
      periprocedural complication was observed and follow-up CT scan showed only a mild
      brain infarct in the MCA territory. After, respectively, 12 and 10 months follow
      up, patients had a favorable outcome with NIHSS 0 and mRS < or = 1. CONCLUSION:
      Endovascular stent-assisted thrombolysis appears to be a promising treatment in
      tandem occlusion due to ICA dissection. Our work underline the potential use of
      self-expandable intracranial stents in symptomatic acute ICA dissection.

PMID- 19756561
TI  - Visual discrimination among patients with depression and schizophrenia and
      healthy individuals using semiquantitative color-coded fast spin-echo T1-weighted
      magnetic resonance imaging.
AB  - INTRODUCTION: Fast spin-echo (FSE) T1-weighted (T1W) magnetic resonance imaging
      (MRI) at 3T, which is sensitive to neuromelanin-related contrast, can
      quantitatively detect signal alterations in the locus ceruleus (LC) and the
      substantia nigra pars compacta (SNc) of depressive and schizophrenic patients;
      however, its qualitative diagnostic performance remains unknown. We investigated
      whether visual interpretation of semiquantitative color maps can be used for
      discriminating between depressive and schizophrenic patients and healthy
      individuals. METHODS: We retrospectively examined 23 patients with major
      depression, 23 patients with schizophrenia, and 23 age-matched healthy controls
      by using a FSE-T1W MRI technique. Semiquantitative color maps of sections through
      the LC and SNc were visually interpreted by nine raters using a continuous
      confidence rating scale for receiver operating characteristic (ROC) analysis.
      RESULTS: The area under the ROC curve (Az), which reflects the performance in
      differentiating between depressive patients and controls, was 0.88, and the
      sensitivity and specificity at the maximum likelihood were 76% and 83%,
      respectively. In contrast, the Az value, sensitivity, and specificity values
      between schizophrenics and controls and between depressives and schizophrenics
      were 0.66 and 0.69, 42% and 48%, and 82% and 84%, respectively. CONCLUSION:
      Semiquantitative, color-coded FSE-T1W MRI at 3T can be used for visually
      differentiating depressive patients from healthy individuals with a substantially
      high likelihood, but this technique cannot be applied to distinguish
      schizophrenic patients from the other two groups.

PMID- 19756562
TI  - Evaluation of the toxicity of onyx compared with n-butyl 2-cyanoacrylate in the
      subarachnoid space of a rabbit model: an experimental research.
AB  - INTRODUCTION: The toxic effects of onyx, its solvent dimethyl sulphoxide (DMSO),
      and n-butyl 2-cyanoacrylate (NBCA) were evaluated after infusion into the
      subaracnoid space of a rabbit model. METHODS: Each of the two various
      concentrations of onyx, pure DMSO, NBCA, and normal saline solution were
      percutaneously infused into the pontocerebellar cisternae of 39 domestic male
      albino rabbits, after which, the brain stems and medial cerebellar tissues were
      harvested for biochemical and histopathological studies. RESULTS: The specimens
      infused in various concentration of onyx, DMSO, and NBCA showed neural tissue
      necrosis and edema with inflammatory cell infitration in the acute stage.
      Although the mean values of the lipid peroxidase in the control, saline, and NBCA
      groups were found to be almost similar, they were found to be low in the onyx and
      DMSO groups. CONCLUSION: This experimental study suggests that NBCA, and various
      concentrations of onyx and DMSO have toxic effects on the neural tissues of
      rabbits when infused into the subarachnoid space.

PMID- 19756563
TI  - Phase-contrast MRI and 3D-CISS versus contrast-enhanced MR cisternography on the
      evaluation of the aqueductal stenosis.
AB  - INTRODUCTION: In the current study, we aimed to compare the diagnostic efficacies
      of phase-contrast magnetic resonance imaging (PC-MRI) and three-dimensional
      constructive interference in steady-state (3D-CISS) sequence over detection of
      aqueductal stenosis (AS) on the basis of contrast-enhanced magnetic resonance
      cisternography (MRC). METHODS: Twenty-five patients with clinically and
      radiologically suspected AS were examined by PC-MRI, 3D-CISS, and MRC. Axial
      sagittal PC-MRI and sagittal 3D-CISS were applied to view the cerebral aqueduct.
      Following injection of 0.5-1 ml intrathecal gadolinium diethylenetriamine
      pentaacetic acid (Gd-DTPA) injection, postcontrast MRC images were obtained in
      three planes in early and late phases. Aqueductal patency was scored as follows:
      grade 0, normal; grade 1, partial narrowing; and grade 2, complete obstruction.
      Results of PC-MRI and 3D-CISS were compared with the findings of MRC. RESULTS: In
      PC-MRI, seven cases were assessed as grade 0, 16 cases grade 1, and two cases
      grade 2. As a result of 3D-CISS sequence, eight cases were evaluated as grade 0,
      12 cases grade 1, and five cases grade 2. Based on MRC, nine cases were assessed
      as grade 0, whereas nine and seven cases were evaluated to be grades 1 and 2,
      respectively. Five cases that demonstrated partial patency in PC-MRI or 3D-CISS
      showed complete obstruction by MRC. CONCLUSION: PC-MRI is helpful in confirming
      the AS. However, positive flow does not necessarily exclude the existence of AS.
      3D-CISS sequence provides excellent cerebrospinal fluid-to-aqueduct contrast,
      allowing detailed study of the anatomic features of the aqueduct. MRC should be
      performed on patients who demonstrate suspected AS findings on PC-MRI and/or 3D
      CISS sequences.

PMID- 19756564
TI  - Technical feasibility of 2D-3D coregistration for visualization of self
      expandable microstents to facilitate coil embolization of broad-based
      intracranial aneurysms: an in vitro study.
AB  - INTRODUCTION: The use of self-expandable microstents for treatment of broad-based
      intracranial aneurysms is widely spread. However, poor fluoroscopic visibility of
      the stents remains disadvantageous during the coiling procedure. Flat detector
      angiographic computed tomography (ACT) provides high resolution imaging of
      microstents even though integration of this imaging modality in the
      neurointerventional workflow has not been widely reported. METHODS: An acrylic
      glass model was used to simulate the situation of a broad-based sidewall
      aneurysm. After insertion of a self-expandable microstent, ACT was performed. The
      resulting 3D dataset of the Microstent was subsequently projected into a
      conventional 2D fluoroscopic roadmap. This 3D visualization of the stent
      supported the coil embolization procedure of the in vitro aneurysm. RESULTS: In
      vitro 2D-3D coregistration with integration of 3D ACT data of a self-expandable
      microstent in a conventional 2D roadmap is feasible. CONCLUSIONS: Unsatisfying
      stent visibility constrains clinical cases with complex parent vessel anatomy and
      challenging aneurysm geometry; hence, this technique potentially may be useful in
      such cases. In our opinion, the clinical feasibility and utility of this new
      technique should be verified in a clinical aneurysm embolization study series
      using 2D-3D coregistration.

PMID- 19756565
TI  - Correlation of signal intensity ratio on orbital MRI-TIRM and clinical activity
      score as a possible predictor of therapy response in Graves' orbitopathy--a pilot
      study at 1.5 T.
AB  - INTRODUCTION: This study seeks to describe the predictive value of the signal
      intensity ratio (SIR) in magnetic resonance imaging-turbo inversion recovery
      magnitude (MRI-TIRM) in patients with Graves' orbitopathy (GO) with regard to
      predictability of therapy response. METHODS: Included in this prospective pilot
      study were 36 consecutive patients with GO and 25 control subjects. Patients were
      clinically assessed according to the European Group on Graves' Orbitopathy
      recommendations with active GO defined by a clinical activity score (CAS) > or =
      3. On magnetic resonance (MR) imaging, muscle inflammation was measured with a
      region of interest set within the brightest extra-ocular muscle both on coronal
      turbo inversion recovery magnitude (TIRM) and on fat suppressed gadolinium
      enhanced T1-weighted sequences. To calculate the SIR, the measured signal
      intensity was set in proportion to that of the ipsilateral temporalis muscle.
      RESULTS: Signal intensity ratio in coronal T2-weighted TIRM sequences in either
      group ranged from 1.22 to 4.92 (mean 2.04) in patients with GO and from 1.18 to
      2.4 (mean 1.63) in controls without GO. The observed differences were significant
      on the TIRM sequences (right eye p = 0.023; left eye p = 0.022), whereas, no
      significant differences could be detected on the T1-weighted sequences (right eye
      p = 0.396; left eye p = 0.498). A cut off value of SIR > 2.5 for a CAS > or = 4
      to discriminate active from inactive patients was statistically calculated.
      CONCLUSION: T2 relaxation time is a reliable tool in detecting active GO. The
      difference in T2-SIR versus T1-SIR is helpful to distinguish inflammatory oedema
      of the extra ocular muscles from intra-orbital congestion due to reduced venous
      outflow.

PMID- 19756568
TI  - Pattern of family history in stone patients.
AB  - Genetic predisposition to urolithiasis is a much discussed topic. The objective
      of this paper is to identify the types of family members of proved urinary stone
      patients, who have a history of urinary stone formation. The study population
      consisted of 2,157 urinary stone patients interviewed in 2003-2007 in the urinary
      stone clinic. Family members with stone history were classified as group 1--first
      order single (one person in the immediate family-father, mother, siblings, or
      children), group 2--first order multiple (more than one member in the above
      group), group 3--second order single (one person in the blood relatives in family
      -grandparents, grandchildren, uncles, aunts, cousins, etc.) and group 4--second
      order multiple (more than one member in the above group). Of the 2,157 patients
      studied, 349 patients gave positive history of stone disease constituting 16.18%.
      Of these, 321 were males and 28 were females. Subdivision of the family members
      showed that 282 patients (80.80%) had single family member with stones and the
      rest 67 (19.20%) had multiple family members with history of stone disease. Group
      1 which constituted one family member in the immediate family had 255
      involvements (father: 88, mother: 16, brother: 135, sister: 2, son: 10, and
      daughter: 4); Group 2 with multiple members in the immediate family constituted
      51 relatives; of these, father and brother combination was the most common with
      35 occurrences. Group 3 with one person in the distant relatives in family namely
      grandparents, grand children, uncles, aunts, cousins, etc. constituted 27
      occurrences and Group 4 with more than one member in the distant family
      constituted 16 occurrences. It is concluded that single family member involvement
      was more than multiple involvements. Males predominated. Stone occurrence was
      more in the immediate family members than distant relatives. Brothers formed the
      most common group to be involved with stone disease. Study of stone risk in the
      family members should be centred on brothers and sons of stone patients.

PMID- 19756569
TI  - Cardiac fibroma in a neonate.

PMID- 19756570
TI  - Osteopetrorickets: infantile malignant osteopetrosis paradoxically complicated by
      rickets.

PMID- 19756573
TI  - Guanidine hydrochloride and urea-induced unfolding of Brugia malayi hexokinase.
AB  - Guanidine hydrochloride and urea-induced unfolding of B. malayi hexokinase
      (BmHk), a tetrameric protein, was examined in detail by using various optical
      spectroscopic techniques, enzymatic activity measurements, and size-exclusion
      chromatography. The equilibrium unfolding of BmHk by guanidine hydrochloride
      (GdmCl) and urea proceeded through stabilization of several unique oligomeric
      intermediates. In the presence of low concentrations of GdmCl, stabilization of
      an enzymatically active folded dimer of BmHk was observed. However an
      enzymatically inactive dimer of BmHk was observed for urea-treated BmHk. This is
      the first report of an enzymatically active dimer of hexokinase from any human
      filarial parasite. Furthermore, although complete recovery of the native enzyme
      was observed on refolding of BmHk samples denatured by use of low concentrations
      of GdmCl or urea, no recovery of the native enzyme was observed for BmHk samples
      denatured by use of high concentrations of GdmCl or urea.

PMID- 19756574
TI  - TCRJ and BCRJ gene segments contain 5' D-segment sequences that contribute to
      repertoire diversity.
AB  - T cell receptor (TCR) and B cell receptors (BCR) junctions, also known as the
      CDR3, are where the V, D, and J gene segments converge, coding for a loop
      structure important for contacting ligands. J segments contribute to the
      formation of the CDR3 loop through their 5' ends that vary in length and show
      high sequence variability. The 5' ends of J segments of TCRalpha genes show
      nucleotide sequence similarities to TCRDdelta segments as high as 89% and show a
      preponderance of murine TCRDdelta2 or human TCRDdelta3 amino acid sequence
      similarities. Surprisingly, most of the 5' ends of TCRJgamma segments show
      nucleotide and amino acid sequence similarities with TCRDbeta segments. All
      murine and human BCRJH segments and most TCRJdelta segments contain amino acid
      sequences at their 5' ends that resemble their own D segments, a finding that is
      not seen with TCRJbeta segments. TCRalpha and TCRgamma genes thus make up for
      their lack of separate D segments with distinct D-like segments that are built
      into the 5' ends of their J segments. Additionally, in some cases, TCR and BCR
      genes that utilize separate D segments also receive additional D-like
      contributions though the 5' ends of their J segments to add additional diversity
      to their CDR3 loops.

PMID- 19756575
TI  - Biodiversity in aerobic granule membrane bioreactor at high organic loading
      rates.
AB  - The aerobic granular sludge process and the membrane bioreactor process are
      promising, novel environmental bioprocesses for the reclamation of industrial and
      municipal wastewaters. They are practical and have attracted much research
      interest. The combination of these two processes in the aerobic granular membrane
      bioreactor (AGMBR), yields reclaimed water of high quality in a compact reactor.
      Information on the microbial community in an AGMBR operated at a high organic
      loading rate is lacking. This study elucidates the microbial dynamics in acetate
      fed AGMBR operated in sequencing batch reactor mode. The structure of the
      microbial community revealed by denaturing gradient gel electrophoresis,
      demonstrates the dominance of the denitrifying microbial community, which is
      affiliated with members of the families Comamonadaceae and Alcaligenaceae, of the
      class Betaproteobacteria. The role of the predominant strains in the AGMBR is
      discussed.

PMID- 19756576
TI  - Characterization of a chimeric enzyme comprising feruloyl esterase and family 42
      carbohydrate-binding module.
AB  - We engineered a chimeric enzyme (AwFaeA-CBM42) comprising of type-A feruloyl
      esterase from Aspergillus awamori (AwFaeA) and family 42 carbohydrate-binding
      module (AkCBM42) from glycoside hydrolase family 54 alpha-L-arabinofuranosidase
      of Aspergillus kawachii. The chimeric enzyme was successfully produced in Pichia
      pastoris and accumulated in the culture broth. The purified chimeric enzyme had
      an apparent relative molecular mass (M(r)) of 53,000. The chimeric enzyme binds
      to arabinoxylan; this indicates that the AkCBM42 in AwFaeA-CBM42 binds to
      arabinofuranose side chain moiety of arabinoxylan. The thermostability of the
      chimeric enzyme was greater than that of AwFaeA. No significant difference of the
      specific activity toward methyl ferulate was observed between the AwFaeA and
      chimeric enzyme, but the release of ferulic acid from insoluble arabinoxylan by
      the chimeric enzyme was approximately 4-fold higher than that achieved by AwFaeA
      alone. In addition, the chimeric enzyme and xylanase acted synergistically for
      the degradation of arabinoxylan. In conclusion, the findings of our study
      demonstrated that the components of the AwFaeA-CBM42 chimeric enzyme act
      synergistically to bring about the degradation of complex substrates and that the
      family 42 carbohydrate-binding module has potential for application in the
      degradation of polysaccharides.

PMID- 19756577
TI  - Tolerance and stress response to ethanol in the yeast Saccharomyces cerevisiae.
AB  - Eukaryotic cells have developed diverse strategies to combat the harmful effects
      of a variety of stress conditions. In the model yeast Saccharomyces cerevisiae,
      the increased concentration of ethanol, as the primary fermentation product, will
      influence the membrane fluidity and be toxic to membrane proteins, leading to
      cell growth inhibition and even death. Though little is known about the complex
      signal network responsible for alcohol stress responses in yeast cells, several
      mechanisms have been reported to be associated with this process, including
      changes in gene expression, in membrane composition, and increases in chaperone
      proteins that help stabilize other denatured proteins. Here, we review the recent
      progresses in our understanding of ethanol resistance and stress responses in
      yeast.

PMID- 19756578
TI  - Engineering Klebsiella oxytoca for efficient 2, 3-butanediol production through
      insertional inactivation of acetaldehyde dehydrogenase gene.
AB  - Ethanol was a major byproduct of 2,3-butanediol (2,3-BD) fermentation by
      Klebsiella oxytoca ME-UD-3. In order to achieve a high efficiency of 2,3-BD
      production, K. oxytoca mutants deficient in ethanol formation were successfully
      constructed by replace the aldA gene coding for aldehyde dehydrogenase with a
      tetracycline resistance cassette. The results suggested that inactivation of aldA
      led to a significantly improved 2,3-BD production. The carbon flux to 2,3-BD was
      enhanced by eliminating the byproducing ethanol and at the same time reducing the
      accumulation of another byproduct acetoin. At last, by fed-batch culturing of the
      mutant, the final 2,3-BD titer up to 130 g/l with the productivity of 1.63 g/l.h
      and the 2,3-BD yield relative to glucose of 0.48 g/g was obtained.

PMID- 19756579
TI  - Chitinase of Bacillus licheniformis from oyster shell as a probe to detect chitin
      in marine shells.
AB  - Bacillus licheniformis CBFOS-03 is a chitinase producing bacteria isolated from
      oyster (Crassostrea gigas) shell waste. We have cloned and expressed the chi18B
      gene of B. licheniformis CBFOS-03, which encodes a glycohydrolase family 18
      chitinase (GH18). Chi18B is a predicted 598 amino acid protein that consists of a
      catalytic domain (GH18), a fibronectin type III domain (Fn3), and a chitin
      binding domain (CBD). Purified Chi18B showed optimum chitinase activity at pH 9
      and 55 degrees C, and activity was stimulated with 25 mM Mn2+. In kinetic
      analysis, Chi18B showed Km values of 9.07 +/- 0.65 microM and 129.27 +/- 0.38
      microM with the substrates 4-methylumbelliferyl-N-N'-diacetylchitobiose and alpha
      chitin, respectively. Studies of C-terminal deletion constructs revealed that the
      GH18 domain with one amino acid in C-terminal region was sufficient for chitinase
      activity; however, fusions of full length and CBD-deleted constructs to green
      florescent protein (GFP) and yellow florescent protein (YFP) suggest that the C
      terminus is supposedly important in binding to shell powder. Full length Chi18B
      with GFP showed green fluorescence with oyster shell powder, but GH18+Fn3 with
      GFP did not. Similarly, full length Chi18B with YFP showed yellow fluorescence
      with clam (Chamelea gallina) shell and disk abalone (Haliotis discus) shell
      powder, but GH18+Fn3 with YFP construct did not. So, the CBD domain of Chi18B
      appears to play an important role in binding of oyster and other marine shells.
      It is likely to be used as a probe to identify the presence of chitin in marine
      shells like oyster shell, clam shell, and disk abalone shell using fusions of
      Chi18B with fluorescent proteins.

PMID- 19756580
TI  - In vitro synthesis of heparosan using recombinant Pasteurella multocida heparosan
      synthase PmHS2.
AB  - In vertebrates and bacteria, heparosan the precursor of heparin is synthesized by
      glycosyltransferases via the stepwise addition of UDP-N-acetylglucosamine and UDP
      glucuronic acid. As heparin-like molecules represent a great interest in the
      pharmaceutical area, the cryptic Pasteurella multocida heparosan synthase PmHS2
      found to catalyze heparosan synthesis using substrate analogs has been studied.
      In this paper, we report an efficient way to purify PmHS2 and to maintain its
      activity stable during 6 months storage at -80 degrees Celsius using His-tag
      purification and a desalting step. In the presence of 1 mM of each nucleotide
      sugar, purified PmHS2 synthesized polymers up to an average molecular weight of
      130 kDa. With 5 mM of UDP-GlcUA and 5 mM of UDP-GlcNAc, an optimal specific
      activity, from 3 to 6 h of incubation, was found to be about 0.145
      nmol/microg/min, and polymers up to an average of 102 kDa were synthesized in 24
      h. In this study, we show that the chain length distribution of heparosan
      polymers can be controlled by change of the initial nucleotide sugar
      concentration. It was observed that low substrate concentration favors the
      formation of high molecular weight heparosan polymer with a low polydispersity
      while high substrate concentration did the opposite. Similarities in the
      polymerization mechanism between PmHS2, PmHS1, and PmHAS are discussed.

PMID- 19756581
TI  - Global transcriptome analysis of the Mycobacterium bovis BCG response to sodium
      hypochlorite.
AB  - Tuberculosis is a common and often deadly infectious disease caused by
      mycobacteria, mainly Mycobacterium tuberculosis and infrequently by other
      subspecies of the M. tuberculosis complex, such as M. bovis. Sodium hypochlorite
      (bleach) is routinely used in hospitals and health care facilities for surface
      sterilization; however, the modes of action of bleach on M. bovis BCG and how
      this organism develops resistance to sodium hypochlorite have not been
      elucidated. In this study, we performed a global toxicogenomic analysis of the M.
      bovis response to 2.5 mM sodium hypochlorite after 10 and 20 min. M. bovis BCG
      growth was monitored by measuring the quantity of ATP in picomoles produced over
      a short exposure time (10-60 min) to sodium hypochlorite. This study revealed
      significant regulation of oxidative stress response genes of M. bovis BCG, such
      as oxidoreductase, peroxidase, heat shock proteins and lipid transport, and
      metabolism genes. We interpreted this response as a potentially more lethal
      interplay between fatty acid metabolism, sulfur metabolism, and oxidative stress.
      Our results also suggest that sodium hypochlorite repressed transcription of
      genes involved in cell wall synthesis of M. bovis. This study shows that the
      treatment of M. bovis BCG with bleach inhibits the biosynthesis of outer cell
      wall mycolic acids and also induces oxidative damage.

PMID- 19756582
TI  - Aptamers and riboswitches: perspectives in biotechnology.
AB  - Aptamers are short, single stranded nucleic acids which bind a wide range of
      different ligands with extraordinary high binding affinity and specificity. The
      steadily increasing number of aptamers is accompanied by an expanding range of
      applications in biotechnology. We will describe new developments in the field
      including the use of aptamers for conditional gene regulation and as biosensors.
      In addition, we will discuss the potential of aptamers as tags to visualize RNA
      and protein distribution in living cells and as therapeutics. Furthermore, we
      will consider biotechnological applications of riboswitches for gene regulation
      and as drug target.

PMID- 19756583
TI  - A novel alpha-amylase from the cyanobacterium Nostoc sp. PCC 7119.
AB  - Little information is yet available on the alpha-amylases of cyanobacteria. Here,
      the presence of an alpha-amylase in the cyanobacterium Nostoc sp. PCC 7119 is
      first demonstrated. A gene (amy1) encoding a cytoplasmic alpha-amylase (Amy1)
      protein has been identified, cloned, and overexpressed in Escherichia coli cells.
      The recombinant protein is a 56.7-kDa monomer, which has been purified to
      electrophoretic homogeneity by affinity chromatography. The substrate specificity
      and end product analyses confirm that it is a calcium-dependent alpha-amylase
      enzyme, which exhibits its maximum activity at 31 degrees C and at pH between 6.5
      and 7.5. The Amy1 protein breaks down mainly starch, is also able to cleave
      glycogen and dextrin, and exhibits no activity against xylan or pullulan. So the
      enzyme cannot efficiently attack the maltodextrins with degrees of polymerization
      below that of maltooctaose. Maltotriose, maltose, and maltotetraose are the major
      products of the enzymatic reaction with starch as substrate. The enzyme shows a
      very high turnover number against soluble potato starch (3,420 +/- 270 s(-1)), as
      compared with other alpha-amylases reported in the literature. The high catalytic
      efficiency and relatively low optimum temperature of the Nostoc Amy1 protein make
      this previously unexplored group of cyanobacterial enzymes of great interest for
      further physiological studies and industrial applications.

PMID- 19756584
TI  - Characterization and kinetic analysis of a thermostable GH3 beta-glucosidase from
      Penicillium brasilianum.
AB  - A GH3 beta-glucosidase (BGL) from Penicillium brasilianum was purified to
      homogeneity after cultivation on a cellulose and xylan rich medium. The BGL was
      identified in a genomic library, and it was successfully expressed in Aspergillus
      oryzae. The BGL had excellent stability at elevated temperatures with no loss in
      activity after 24 h of incubation at 60 degrees C at pH 4-6, and the BGL was
      shown to have significantly higher stability at these conditions in comparison to
      Novozym 188 and to other fungal GH3 BGLs reported in the literature. The BGL had
      significant lower affinity for cellobiose compared with the artificial substrate
      para-nitrophenyl-beta-D-glucopyranoside (pNP-Glc) and further, pronounced
      substrate inhibition using pNP-Glc. Kinetic studies demonstrated the high
      importance of using cellobiose as substrate and glucose as inhibitor to describe
      the inhibition kinetics of BGL taking place during cellulose hydrolysis. A novel
      assay was developed to characterize this glucose inhibition on cellobiose
      hydrolysis. The assay uses labelled glucose-13C6 as inhibitor and subsequent mass
      spectrometry analysis to quantify the hydrolysis rates.

PMID- 19756585
TI  - DNA profiling of complex bacterial populations: toxic cyanobacterial blooms.
AB  - Cyanobacteria are prokaryotic photosynthetic living organisms that inhabit our
      planet for over three billion years. With a worldwide distribution, they can be
      found in all types of environments: fresh, brackish and saltwater as well as
      terrestrial. Though beneficial in the development of life on earth, they also
      constitute a serious risk to our ecosystems since they can biologically produce
      harmful secondary metabolites named cyanotoxins. When studying cyanobacteria and
      their cyanotoxins, several methodologies have been applied with an increasing
      relevance to molecular methods. Therefore, the aim of this review is to describe
      alternative molecular methods that can be used as alternative methods for the
      identification of cyanobacteria. More traditional chemotaxonomic methods are
      discussed briefly as are the standard and somewhat dated techniques for assessing
      genome content for taxonomic classification schemes. The use of DNA amplification
      technology has been applied to the systematics and phylogeny of many bacterial
      groups, and the optimisation of methods for rapid identification and
      classification of cyanobacteria are presented. Together with novel methods
      developed for these photosynthetic microorganisms, the generated DNA profiles
      have been utilised to study cyanobacterial bloom population diversity and
      prediction of strain toxigenicity. Finally, the genotypes found were applied to a
      variety of phylogenetic analyses; trees were reconstructed and compared to the
      current morphological system of classification. The ecology and diversity of the
      cyanobacteria is discussed with respect to the derived molecular phylogenies and
      systematics.

PMID- 19756586
TI  - Inhibition of Candida albicans growth by brominated furanones.
AB  - Candida albicans is the most virulent Candida species of medical importance,
      which presents a great threat to immunocompromised individuals such as HIV
      patients. Currently, there are only four classes of antifungal agents available
      for treating fungal infections: azoles, polyenes, pyrimidines, and echinocandins.
      The fast spread of multidrug resistant C. albicans strains has increased the
      demand for new antifungal drugs. In this study, we demonstrate the antifungal
      activity of brominated furanones on C. albicans. Studying the structure and
      activity of this class of furanones reveals that the exocyclic vinyl bromide
      conjugated with the carbonyl group is the most important structural element for
      fungal inhibition. Furthermore, gene expression analysis using DNA microarrays
      showed that 3 microg/mL of 4-bromo-5Z-(bromomethylene)-3-butylfuran-2-one (BF1)
      upregulated 32 C. albicans genes with functions of stress response, NADPH
      dehydrogenation, and small-molecule transport, and repressed 21 genes involved
      mainly in cell-wall maintenance. Interestingly, only a small overlap is observed
      between the gene expression changes caused by the representative brominated
      furanone (BF1) in this study and other antifungal drugs reported in literature.
      This result suggests that brominated furanones and other antifungal drugs may
      target different fungal proteins or genes. The existence of such new targets
      provides an opportunity for developing new agents to control fungal pathogens
      which are resistant to currently available drugs.

PMID- 19756587
TI  - DyP-like peroxidases of the jelly fungus Auricularia auricula-judae oxidize
      nonphenolic lignin model compounds and high-redox potential dyes.
AB  - The jelly fungus Auricularia auricula-judae produced an enzyme with manganese
      independent peroxidase activity during growth on beech wood (approximately 300 U
      l(-1)). The same enzymatic activity was detected and produced at larger scale in
      agitated cultures comprising of liquid, plant-based media (e.g. tomato juice
      suspensions) at levels up to 8,000 U l(-1). Two pure peroxidase forms (A.
      auricula-judae peroxidase (AjP I and AjP II) could be obtained from respective
      culture liquids by three chromatographic steps. Spectroscopic and electrophoretic
      analyses of the purified proteins revealed their heme and peroxidase nature. The
      N-terminal amino acid sequence of AjP matched well with sequences of fungal
      enzymes known as "dye-decolorizing peroxidases". Homology was found to the N
      termini of peroxidases from Marasmius scorodonius (up to 86%), Thanatephorus
      cucumeris (60%), and Termitomyces albuminosus (60%). Both enzyme forms catalyzed
      not only the conversion of typical peroxidase substrates such as 2,6
      dimethoxyphenol and 2,2'-azino-bis(3-ethylthiazoline-6-sulfonate) but also the
      decolorization of the high-redox potential dyes Reactive Blue 5 and Reactive
      Black 5, whereas manganese(II) ions (Mn(2+)) were not oxidized. Most remarkable,
      however, is the finding that both AjPs oxidized nonphenolic lignin model
      compounds (veratryl alcohol; adlerol, a nonphenolic beta-O-4 lignin model dimer)
      at low pH (maximum activity at pH 1.4), which indicates a certain ligninolytic
      activity of dye-decolorizing peroxidases.

PMID- 19756588
TI  - Hereditary bone dysplasia with pathological fractures  and nodal
      osteoarthropathy.
AB  - A father and daughter both had multiple pathological fractures and nodal
      osteoarthropathy. The father, aged 50 years, had at least 20 healed fractures of
      the axial and appendicular skeleton, sustained by minor trauma over his 50-year
      lifespan, many of which had been surgically fixed prior to his first presentation
      to us. Fractures of the clavicles, thoracic cage and long bones of the arms and
      legs, had healed with malalignment and deformity. Healed fractures were
      complicated by ankylosis of the cervical vertebrae and both elbows. He also had
      osteoarthritis of the hands, with exuberant osteophytosis, and profound
      perceptive deafness. His general health was good, his intellect and facies were
      normal, and his sclerae were white. The daughter, aged 27 years, had sustained at
      least seven fractures of the axial and appendicular skeleton following trivial
      injuries, in distribution similar to those of the father.She had also experienced
      painful swelling of the fingers,which preceded progressive development of nodal
      osteoarthropathy.Her hearing was normal. In both individuals,biochemical and
      immunological investigations yielded normal results. It was not possible for
      molecular studies to be undertaken. Pedigree data were consistent with autosomal
      dominant transmission, and this disorder appeared to be a previously undocumented
      heritable skeletal dysplasia.

PMID- 19756589
TI  - Intra and inter-examiner reliability of the subacromial impingement index.
AB  - OBJECTIVE: The present study aimed to assess the reliability of intra and inter
      examiner subacromial impingement index (SII) measures obtained from radiographs.
      MATERIALS AND METHODS: Thirty-six individuals were enrolled and divided into two
      groups: control group, composed of 18 volunteers in good general health without
      shoulder problems, and a group of 18 patients with subacromial impingement
      syndrome (SIS). Radiographic images were taken with the dominant upper limb in
      neutral rotation, while the volunteers held their arm at 90 degrees of abduction
      in the frontal plane. The beam of radiation at 30 degrees craniocaudal
      inclination was used to provide an antero-posterior image view. Three blinded
      examiners each performed three measurements from the subacromial space (SS) and
      the anatomical neck of the humerus (NH). The SII was calculated as the ratio of
      the SS and the NH measures. The mean values of SII were compared using t-tests.
      The intra-class correlation coefficient (ICC) was used to assess intra- and inter
      examiner reliability of the measures. RESULTS: The mean values of SII were
      greater for the control group (0.12) than for the SIS group (0.08; p = 0.0071).
      SII measurements showed excellent intra (0.96-0.99) and inter-examiner
      reliability (0.94) for both the control and SIS group. CONCLUSION: The results of
      this study show the potential use of the SII; a greater mean value for the
      control group compared to the SIS group and excellent reliability for intra- and
      inter-examiner measurement. Validation studies of the index should be conducted
      to correlate the index with clinical findings from subacromial impingement
      syndrome.

PMID- 19756590
TI  - Determination of digitised radiograph magnification factors for pre-operative
      templating in hip prosthesis surgery.
AB  - OBJECTIVE: With digital radiography development, information technology (IT)
      companies have developed specific software for templating procedures, requiring
      individual magnification assessments for each patient. The aim of this study was
      to determine the mean magnification factor of digital radiographs and to evaluate
      the possibility of using the mean magnification factor or clinical information in
      templating. MATERIALS AND METHODS: We retrospectively evaluated 100 primary total
      hip arthroplasty digital radiographs using the femoral head prosthesis as a
      calliper to determinate the mean magnification factor. Working on the assumption
      that altitude of the hip during radiograph is decisive in modification of
      magnification factors, we also looked for a correlation between weight, body mass
      index (BMI), altitude and magnification factor. RESULTS: The magnification factor
      was 126% (121-130%). A relationship was found between magnification factor (Mf)
      and weight (Mf = 7.10(-4)x weight (kg) + 1.21), but not BMI. In 98% of cases, if
      the weight-correlated formula is used, the sizing is correct or the error is +/-
      1 mm. With the mean method the sizing is correct or within 1 mm in only 78.2% of
      cases. CONCLUSION: Levels of accuracy for the mean magnification factor and the
      weight-correlated formula are not as high as individual assessments using a
      calliper; however, they could be used in everyday practice where individual
      magnification factors have not been calculated.

PMID- 19756591
TI  - Role of PET/CT in malignant pediatric lymphoma.
AB  - INTRODUCTION: Malignant pediatric lymphoma accounts for 10-15% of all pediatric
      cancers, (representing 2-3% of all malignancies), with a peak incidence between 5
      9 years. Chemotherapy is usually the first and most common mode of treatment. The
      choice of treatment and prediction of prognosis depend on the histological type
      of tumor, initial staging, evaluating treatment response, and detection of early
      recurrence. Conventional imaging modalities have many limitations. PET/CT is more
      accurate, however so far the literature lacks the results of a large group of
      patients. AIM OF STUDY: To report the role of PET/CT in the above-mentioned
      objectives at the newly established Children's Cancer Hospital in Cairo, Egypt,
      which is one of the busiest dedicated pediatric oncology centers of such purposes
      in the world. All findings were proven by histopathology, clinically, and by
      clinical follow-up. PATIENT POPULATION: A total of 152 patients (35 girls and 117
      boys) with histologically proven malignant lymphoma (117 HD, 35 NHL) were
      included in this study. They were divided into four groups. Group I: 41 patients
      for initial staging. Group II: 51 patients for evaluating early treatment
      response after two to three cycles of chemotherapy. Group III: 42 patients for
      evaluating treatment response 4-8 weeks after the end of their treatment. Group
      IV: 18 patients evaluated for long-term follow-up. Results of PET/CT were
      compared with the other conventional imaging modalities (CIM). RESULTS: The
      sensitivity, specificity, accuracy, and positive and negative predictive values
      of PET/CT and CIM were as follows: In Group I: PET/CT modified staging and
      treatment in 11 out of 41 cases (26.8%), upstaged 5(12.2%) patients and down
      staged six (14.6%) patients. Group II: 100%, 97.7%, 98%, 85.7%, 100%,
      respectively, for PET/CT and 83%, 66.6%, 68.6%, 25%, 96.7% for CIM respectively
      Group III: At the end of chemotherapy 100%, 90.9%, 92.8%, 75%, 100%,
      respectively, for PET/CT and 55.5%, 57.5%, 57.1%, 26.3%, 82.6% for CIM,
      respectively. Group IV: For long-term follow-up, all the parameters scored 100%
      for PET/CT, 100%, 38.4%, 72.2%, 50%, 100% for CIM, respectively. CONCLUSION:
      PET/CT in pediatric lymphoma is more accurate than CIM. We recommend that it
      should be the first modality for all purposes in initial staging, evaluating
      treatment response and follow-up.

PMID- 19756592
TI  - Predictive factors of [(11)C]choline PET/CT in patients with biochemical failure
      after radical prostatectomy.
AB  - PURPOSE: Detection of recurrence in prostate cancer patients with biochemical
      failure after radical prostatectomy by [(11)C]choline PET/CT depends on the
      prostate-specific antigen (PSA) level. The role of other clinical and
      pathological variables has not been explored. METHODS: A total of 2,124 prostate
      cancer patients referred to our Institution for [(11)C]choline PET/CT from
      December 2004 to January 2007 for restaging of disease were retrospectively
      considered for this study. Inclusion criteria were: previous treatment by radical
      prostatectomy, and biochemical failure, defined as at least two consecutive PSA
      measurements of >0.2 ng/ml. These criteria were met for 358 patients. Binary
      logistic analysis was used to investigate the predictive factors of
      [(11)C]choline PET/CT. PET/CT findings were validated using criteria based on
      histological analysis, and follow-up clinical and imaging data. Receiver
      operating characteristic (ROC) analysis was used to assess the performance of
      [(11)C]choline PET/CT in relation to PSA levels. RESULTS: The mean PSA level was
      3.77 +/- 6.94 ng/ml (range 0.23-45 ng/ml; median 1.27 ng/ml). PET/CT was positive
      for recurrence in 161 of 358 patients (45%). On an anatomical region basis,
      [(11)C]choline pathological uptake was observed in lymph nodes (107/161 patients,
      66%), prostatectomy bed (55/161 patients, 34%), and in the skeleton (46/161
      patients, 29%). PET/CT findings were validated using histological criteria
      (46/358, 13%), and follow-up clinical and imaging criteria (312/358, 87%).
      Sensitivity, specificity, positive predictive value, negative predictive value,
      and overall accuracy were, respectively, 85%, 93%, 91%, 87%, and 89%. In
      multivariate analysis, high PSA levels, advanced pathological stage, previous
      biochemical failure and older age were significantly (P < 0.05) associated with
      an increased risk of positive PET/CT findings. The percentage of positive scans
      was 19% in those with a PSA level between 0.2 and 1 ng/ml, 46% in those with a
      PSA level between 1 and 3 ng/ml, and 82% in those with a PSA level higher than 3
      ng/ml. ROC analysis showed that PET/CT-positive and PET/CT-negative patients
      could be best distinguished using a PSA cut-off value of 1.4 ng/ml. CONCLUSIONS:
      In addition to PSA levels, pathological stage, previous biochemical failure and
      age should be considered by physicians when referring prostate cancer patients
      with biochemical failure after radical prostatectomy to [(11)C]choline PET/CT.

PMID- 19756593
TI  - Relationship between HLA class I antigen processing machinery component
      expression and the clinicopathologic characteristics of bladder carcinomas.
AB  - PURPOSE: The goal of this study was to analyze protein expression of antigen
      processing machinery (APM) components in bladder carcinoma (BC), and to assess
      the clinical significance of defects in their expression. EXPERIMENTAL DESIGN:
      Tissue from 167 cystectomies for primary BC was used to create a tissue
      microarray. 128 tumors were urothelial carcinoma (UC). Immunohistochemistry was
      performed using 14 monoclonal antibodies to APM components (beta2-microglobulin,
      calnexin, calreticulin, delta, Z, MB1, LMP2, LMP7, LMP10, HLA class I heavy
      chain, tapasin, TAP1, TAP2 and ERp57) and MHC class I-related antigen (MICA).
      Sections of normal urothelium from six subjects were used as controls. RESULTS:
      All APM components except MB1, LMP2 and TAP2 had significantly lower staining in
      UC than in normal urothelium. No significant differences were found in APM
      component scores between different grades of UC. Squamous cell carcinoma had the
      highest scores, with UC intermediate and other types of BC lowest. High-stage UC
      demonstrated significantly lower staining for calnexin, LMP2, LMP7 and LMP10 than
      low-stage UC. With mean 3.6 years follow up, significantly worse survival was
      associated with a higher delta score in UC (P = 0.038) and a lower calreticulin
      score in all tumor types (P = 0.028). CONCLUSIONS: Most APM components were
      downregulated in UC. High-stage UC had lower scores for immunoproteasome
      components compared to low-stage UC. Delta and calreticulin protein expression
      was associated with survival in UC and in all types of BC, respectively. These
      findings suggest that APM defects play a role in the clinical course of BC and
      should be considered in developing immunotherapeutic approaches for its control.

PMID- 19756594
TI  - Natural killer cell is a major producer of interferon gamma that is critical for
      the IL-12-induced anti-tumor effect in mice.
AB  - Although the anti-tumor effect of IL-12 is mediated mostly by IFNgamma, which
      cell types most efficiently produce IFNgamma and therefore initiate or promote
      the anti-tumor effect of IL-12 has not been clearly determined. In the present
      study, we demonstrated hydrodynamic injection of the IL-12 gene led to prolonged
      IFNgamma production, NK-cell activation and complete inhibition of liver
      metastasis of CT-26 colon cancer cells in wild-type mice, but not in IFNgamma
      knockout mice. NK cells expressed higher levels of STAT4 and upon IL-12
      administration displayed stronger STAT4 phosphorylation and IFNgamma production
      than non-NK cells. Adoptive transfer of wild-type NK cells into IFNgamma knockout
      mice restored IL-12-induced IFNgamma production, NK-cell activation and anti
      tumor effect, whereas transfer of the same number of wild-type non-NK cells did
      not. In conclusion, NK cells are predominant producers of IFNgamma that is
      critical for IL-12 anti-tumor therapy.

PMID- 19756596
TI  - Survivin as an immunotherapeutic target for adult and pediatric malignant brain
      tumors.

PMID- 19756595
TI  - Concurrent vaccination with two distinct vaccine platforms targeting the same
      antigen generates phenotypically and functionally distinct T-cell populations.
AB  - PURPOSE: Studies comparing two or more vaccine platforms have historically
      evaluated each platform based on its ability to induce an immune response and may
      conclude that one vaccine is more efficacious than the other(s), leading to a
      recommendation for development of the more effective vaccine for clinical
      studies. Alternatively, these studies have documented the advantages of a
      diversified prime and boost regimen due to amplification of the antigen-specific
      T-cell population. We hypothesize here that two vaccine platforms targeting the
      same antigen might induce shared and distinct antigen-specific T-cell
      populations, and examined the possibility that two distinct vaccines could be
      used concomitantly. EXPERIMENTAL DESIGN: Using recombinant poxvirus and yeast
      vaccines, we compared the T-cell populations induced by these two platforms in
      terms of serum cytokine response, T-cell gene expression, T-cell receptor
      phenotype, antigen-specific cytokine expression, T-cell avidity, and T-cell
      antigen-specific tumor cell lysis. RESULTS: These studies demonstrate for the
      first time that vaccination with a recombinant poxvirus platform (rV/F
      CEA/TRICOM) or a heat-killed yeast vaccine platform (yeast-CEA) elicits T-cell
      populations with both shared and unique phenotypic and functional
      characteristics. Furthermore, both the antigen and the vector play a role in the
      induction of distinct T-cell populations. CONCLUSIONS: In this study, we
      demonstrate that concurrent administration of two vaccines targeting the same
      antigen induces a more diverse T-cell population that leads to enhanced antitumor
      efficacy. These studies provide the rationale for future clinical studies
      investigating concurrent administration of vaccine platforms targeting a single
      antigen to enhance the antigen-specific immune response.

PMID- 19756598
TI  - Long-term results of intertrochanteric varus osteotomy for dysplastic
      osteoarthritis of the hip.
AB  - The beneficial role of intertrochanteric varus or valgus osteotomy in the
      treatment of hip osteoarthrosis has been recognised since the 1920s. Even today,
      it has an important role to delay the need for hip replacement in younger
      patients. The purpose of this study was to evaluate the long-term results of
      intertrochanteric varus osteotomy for dysplastic osteoarthritis of the hip.
      Between 1980 and 1995, 52 hips with dysplastic osteoarthritis underwent an
      intertrochanteric varus osteotomy. All patients could be followed up after 17.8
      years. Radiographic assessment included centre-edge (CE) angle of Wiberg and
      collodiaphyseal (CCD) angle. Dysplastic hip dislocation was classified according
      to Crowe. Osteoarthritis was graded according to Tonnis. Preoperative
      osteoarthritis was Tonnis grade 1 in 19 hips, grade 2 in 28 and grade 3 in five.
      Complications were also documented. Clinical evaluation included score according
      to Merle d'Aubigne, Harris Hip Score and range of motion. Six of 52 patients
      underwent total hip replacement (THR) within five years after intertrochanteric
      osteotomy. In these cases, preoperative osteoarthritis was grade 3 in four cases
      and grade 2 in one case according to Tonnis. Twenty-five of 52 patients underwent
      THR after an interval of five to ten years after intertrochanteric osteotomy. In
      these cases, preoperative osteoarthritis was grade 3 in one case and grade 2 in
      24 cases according to Tonnis. Sixteen of 52 patients underwent THR after an
      interval of ten to 15 years after intertrochanteric osteotomy. In these cases,
      preoperative osteoarthritis was grade 2 in four cases and grade 1 in 12 cases
      according to Tonnis. In five patients the hip was functioning well after a period
      longer than 15 years. In all these cases osteoarthritis was grade 1 according to
      Tonnis. In 40.4% of patients, THR was delayed longer than ten years. The
      osteotomy performed well at a mean time of 9.7 years after the procedure (range 3
      21). Intertrochanteric varus osteotomy for dysplastic osteoarthritis of the hip
      should be considered in early or mild osteoarthritic changes of the hip. Good
      prognosis with delay of THR of more than ten years can be expected to exceed 40%,
      even when indications are less than optimum.

PMID- 19756599
TI  - Reversal of multidrug resistance by curcumin through FA/BRCA pathway in multiple
      myeloma cell line MOLP-2/R.
AB  - Most patients with multiple myeloma (MM) will relapse eventually due to the
      acquired multidrug resistance (MDR). The objective of this study was to explore
      the reversal effect of curcumin on the MDR of human MM cell line, MOLP-2/R, and
      analyze the role of Fanconi anemia (FA)/BRCA pathway in this process. MOLP-2/R
      was selected by stepwise exposure of parental MOLP-2 cells to increasing
      concentrations of melphalan. The MTT assay was used to detect the reversal ratio
      of curcumin. The FANCD2 monoubiquitination expression was detected by western
      blotting to explore the role of FA/BRCA pathway. Cell cycle, apoptosis, and
      intracellular drug concentration were analyzed by flow cytometry. The results
      indicated that combination of melphalan with curcumin had stronger effects on the
      proliferation inhibition, inducement of apoptosis, G2/M phase arrest, and
      enhancement of intracellular drug concentration than melphalan alone in MOLP-2/R
      cells. These effects were accompanied with inhibition of FA/BRCA pathway by down
      regulation of FANCD2 protein monoubiquitination in a dose-dependent manner. In
      conclusion, curcumin reversed multidrug resistance of MOLP-2/R through inhibition
      of FA/BRCA pathway. The possible mechanisms include (1) reduction of DNA damage
      repair and stimulation of apoptosis of tumor cells through inhibition of FA/BRCA
      pathway, which is important for DNA repair, and (2) achievement of high
      concentration in target cells. Curcumin may be a safe reversal agent of multidrug
      resistance with low-dose DNA cross-linking agents.

PMID- 19756600
TI  - Decreased hemolysis following administration of antioxidant-fermented papaya
      preparation (FPP) to a patient with PNH.

PMID- 19756601
TI  - Dihydroartemisinin improves the efficiency of chemotherapeutics in lung
      carcinomas in vivo and inhibits murine Lewis lung carcinoma cell line growth in
      vitro.
AB  - PURPOSE: Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin,
      has exhibited the strongest antimalarial activity among the derivatives of
      artemisinin. There is growing evidence that DHA has some impact against tumors.
      Our purpose was to evaluate in vitro antitumoral properties of DHA in the murine
      Lewis lung carcinoma (LLC) cell line. At the same time, we observed the
      therapeutic effect of DHA combined with cyclophosphamide (CTX) in the LLC and
      combined with cisplatin (CDDP) in the human non-small cell lung cancer A549
      xenotransplanted carcinoma in vivo. METHODS: Cytotoxicity was measured by 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method, apoptosis was
      measured by AO/EB double staining and flow cytometry. The expression of vascular
      endothelial growth factor (VEGF) receptor KDR/flk-1 was analyzed by western
      blotting and RT-PCR. In vivo activity of DHA combined with CTX or CDDP was
      assayed through tumor growth and metastasis. RESULTS: Dihydroartemisinin
      exhibited high anti-cancer activity in LLC cell line. DHA also induced apoptosis
      of LLC cells and influenced the expression of VEGF receptor KDR/flk-1.
      Furthermore, in both tumor xenografts, a greater degree of growth inhibition was
      achieved when DHA and chemotherapeutics were used in combination. The affection
      by DHA combined CTX on LLC tumor metastasis was significant. CONCLUSIONS:
      Dihydroartemisinin is a potent compound against LLC cell line in vitro. In vivo,
      the combination strategy of DHA and chemotherapeutics holds promise for the
      treatment of relatively large and rapidly growing lung cancers.

PMID- 19756602
TI  - N(3)-o-toluyl-fluorouracil inhibits human hepatocellular carcinoma cell growth
      via sustained release of 5-FU.
AB  - PURPOSE: N(3)-o-toluyl-fluorouracil (TFU), the prodrug of 5-fluorouracil (5-FU),
      is the metabolite of N(1)-acetyl-N(3)-o-toluyl-fluorouracil (atofluding). In the
      present study, we aimed to evaluate the efficacy of TFU on the inhibition of
      human hepatocellular carcinoma cells via sustained release of 5-FU. The
      metabolism of TFU underlying the inhibitory effect was also analyzed. METHODS: In
      vitro assays, inhibition of cell growth by TFU was evaluated by the 3-[4,5
      dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide method. The levels of TFU
      and 5-FU in the cell culture supernatant fluid were measured by high-performance
      liquid chromatography (HPLC). In vivo assays, the efficacy of TFU was evaluated
      in a human hepatocellular carcinoma xenograft mice model after 3 weeks of oral
      administration. The distributions of TFU and 5-FU in plasma and homogenate
      tissues including liver, lung and tumor were determined by HPLC. RESULTS: N(3)-o
      toluyl-fluorouracil weakly inhibited the proliferation of SMMC-7721 and PLC/PRF/5
      cells in the absence of liver microsomal enzymes. In contrast, the inhibition
      rates were significantly increased in the presence of these enzymes. HPLC results
      revealed that TFU was metabolized slowly by liver microsomal enzymes and
      therefore the concentration of 5-FU was gradually increased with a longer
      retention time in cell culture supernatant fluid. The efficacy of TFU was
      confirmed in SMMC-7721 xenografts in Balb/c athymic (nu+/nu+) mice model. TFU
      treatment induced inhibition of SMMC-7721 growth with few side effects. HPLC
      results showed that high levels of TFU were still in liver 48 h after the end of
      oral administration, implying that TFU preferentially accumulated in liver with
      slow conversion to 5-FU by enzymes. This led to a long-lasting concentration of 5
      FU in plasma. Further, a high level of 5-FU was found in tumors with a relatively
      low level in lungs. These results suggest that the metabolite of TFU was
      preferentially converted or taken up by tumor cells. The distributions of 5-FU
      may contribute to its high anti-tumor activity and low adverse reactions in vivo.
      CONCLUSION: These results demonstrate that TFU is a promising prodrug of 5-FU for
      cancer treatment via sustained release of 5-FU in liver.

PMID- 19756603
TI  - Oxidative stress and enhanced paracellular permeability in the small intestine of
      methotrexate-treated rats.
AB  - PURPOSE: We previously demonstrated the increase of reactive oxygen species (ROS)
      production and myeloperoxidase (MPO) activity in the small intestine of
      methotrexate (MTX)-treated rats. In the present study, we investigated the role
      of ROS modulating intestinal mucosal permeability in this damage. METHOD: MTX (20
      mg/kg body weight) was administered to rats intravenously. N-Acetylcysteine (NAC;
      80 mg/kg body wt), an antioxidant and a precursor of glutathione (GSH) was
      administered to rats intraperitoneally to investigate the contribution of ROS to
      the intestinal permeability enhancement. Intestinal permeability was evaluated by
      determining that of a poorly absorbable marker, fluorescein isothiocyanate
      labeled dextran (FD-4; average molecular mass, 4.4 kDa) using the in vitro
      everted intestine technique. The occurrence of oxidative stress in the small
      intestine was assayed by measuring chemiluminescence and thiobarbituric acid
      reactive substances (TBARS) productions in mucosal homogenates of the small
      intestine. RESULTS: The mucosal permeability of FD-4 significantly (p < 0.01)
      increased in MTX-treated rats compared with control rats, as demonstrated by a
      twofold increase of FD-4 permeation clearance. This suggests an increase in
      paracellular permeability. Interestingly, the ROS production was observed
      preceding the increase of paracellular permeability. Treatment with NAC prevented
      the MTX-induced ROS production and the increase of paracellular permeability.
      CONCLUSIONS: NAC protected the small intestine of rats from MTX-induced change in
      paracellular permeability, suggesting that ROS played an important role in the
      enhanced paracellular permeability.

PMID- 19756604
TI  - Bevacizumab induced reversible thrombocytopenia in a patient with recurrent high
      grade glioma: a case report.
AB  - We report a case of bevacizumab (BEV)-induced thrombocytopenia in a 36-year-old
      woman treated with BEV as a single-agent for a recurrent high-grade glioma. The
      thrombocytopenia was both reversible and reproducible on multiple treatment
      cycles. The patient has improved clinically and by brain MR imaging with single
      agent BEV for approximately 7 months to date. She did not have bleeding or
      thromboembolic complications. Treatment delays have been 1-2 weeks relative to a
      conventional plan of treatment, i.e., 10 mg/kg every 2 weeks. This is a rare
      complication that has not been previously reported.

PMID- 19756605
TI  - Pharmacokinetics and enhanced bioavailability of candidate cancer preventative
      agent, SR13668 in dogs and monkeys.
AB  - PURPOSE: SR13668 (2,10-dicarbethoxy-6-methoxy-5,7-dihydro-indolo-(2,3
      b)carbazole), is a new candidate cancer chemopreventive agent under development.
      It was designed using computational modeling based on a naturally occurring
      indole-3-carbinol and its in vivo condensation products. It showed promising anti
      cancer activity and its preclinical toxicology profile (genotoxicity battery and
      subchronic rat and dog studies) was unremarkable. However, it exhibited a very
      poor oral bioavailability (<1%) in both rats and dogs. Therefore, a study was
      initiated to develop and evaluate in dogs and non-human primates formulations
      with a more favorable oral bioavailability. METHODS: Two formulations utilizing
      surfactant/emulsifiers, PEG400:Labrasol and Solutol, were tested in dogs and
      monkeys. Levels of SR13668 were measured in plasma and blood using a high
      performance liquid chromatograph-tandem mass spectrometer system. Non
      compartmental analysis was used to derive pharmacokinetic parameters including
      the bioavailability. RESULTS: The Solutol formulation yielded better
      bioavailability reaching a maximum of about 14.6 and 7.3% in dogs and monkeys,
      respectively, following nominal oral dose of ca. 90 mg SR13668/m(2). Blood levels
      of SR13668 were consistently about threefold higher than those in plasma in both
      species. SR13668 did not cause untoward hematology, clinical chemistry, or
      coagulation effects in dogs or monkeys with the exception of a modest, reversible
      increase in liver function enzymes in monkeys. CONCLUSIONS: The lipid-based
      surfactant/emulsifiers, especially Solutol, markedly enhanced the oral
      bioavailability of SR13668 over that previously seen in preclinical studies.
      These formulations are being evaluated in a Phase 0 clinical study prior to
      further clinical development of this drug.

PMID- 19756606
TI  - Gene expression dynamics in randomly varying environments.
AB  - A simple model of gene regulation in response to stochastically changing
      environmental conditions is developed and analyzed. The model consists of a
      differential equation driven by a continuous time 2-state Markov process. The
      density function of the resulting process converges to a beta distribution. We
      show that the moments converge to their stationary values exponentially in time.
      Simulations of a two-stage process where protein production depends on mRNA
      concentrations are also presented demonstrating that protein concentration tracks
      the environment whenever the rate of protein turnover is larger than the rate of
      environmental change. Single-celled organisms are therefore expected to have
      relatively high mRNA and protein turnover rates for genes that respond to
      environmental fluctuations.

PMID- 19756607
TI  - An islet population model of the endocrine pancreas.
AB  - An islet population model is proposed for pancreatic insulin secretion. Without
      detailing the chain of biochemical events giving rise to the delivery of insulin
      packets, the effect of the islets' bursting response to varying glucose
      concentration is described by a simple second order nonlinear model, of the same
      functional form for all islets, but with a random distribution of parameter
      values over the one million islets considered. The islet equations are coupled to
      a traditional model of the glucose/insulin dynamics to complete a description of
      the feed-back control of the glucose/insulin system. The model is thus based upon
      the completely random cooperation of a large number of independent controllers,
      all reacting to the same prevailing plasma glucose concentrations, but with
      distributed reaction characteristics. It is shown that the proposed model is able
      to replicate in silico different observed phenomena such as low frequency
      glycemia-insulinemia oscillations (ultradian oscillations, with a period between
      50 and 150 min, amplified by constant glucose administration and entrained by an
      oscillating exogenous glucose infusion), as well as concordant induction of high
      frequency insulin oscillations by a rapid periodic pulsatile glucose infusion. In
      order to reproduce by simulation all of the above observed phenomena, a single
      set of (hyper-)parameters has been used throughout, showing that it is indeed
      possible that a single model may explain the results of several published
      experimental protocols.

PMID- 19756608
TI  - Synchronized oscillation of the segmentation clock gene in vertebrate
      development.
AB  - In vertebrate somitogenesis, "segmentation clock" genes (her in zebrafish, hes in
      mouse, and hairy in chick) show oscillation, synchronized over nearby cells
      through intercellular interaction. In zebrafish, neighboring cells interact by
      Delta-Notch signaling to realize synchronization. Under Delta-Notch, however, a
      cell with a high expression of the segmentation clock gene tends to suppress its
      expression in adjacent cells, which might produce spatial heterogeneity instead
      of synchronized oscillation. Here we studied the conditions under which pre
      somitic mesoderm cells show synchronized oscillation of gene expression
      mathematically. We adopted a model that explicitly considers the kinetics of the
      mRNA and proteins of the segmentation clock gene and cell-cell interaction via
      Delta-Notch signaling. From statistical study of a model with randomly generated
      parameters, we revealed how the likelihood that the system generates stable
      synchronized oscillation depends on the rate of each reaction in the gene-protein
      kinetics.

PMID- 19756610
TI  - [Pediatric pathology: an interdisciplinary profession].

PMID- 19756611
TI  - [Diagnostic and therapy of salivary gland diseases: relevant aspects for the
      pathologist from the clinical perspective].
AB  - Significant progress in the diagnosis and therapy of salivary gland diseases has
      been made in recent years. The new technique of diagnostic and interventional
      sialendoscopy has made an important contribution and is indicated in every case
      of obstructive sialadenitis. The number of open resections of salivary glands due
      to stones will clearly decrease in the future in favor of endoscopic removal. Due
      to recent publications on the appropriate extent of salivary gland resection in
      benign tumors, more and more specimens with reduced cuffs of healthy salivary
      gland tissue will be sent to the pathologists. Ultrasound will stay the procedure
      of first choice for imaging of salivary gland diseases in Germany. In combination
      with fine-needle aspiration cytology high sensitivity and specificity for the
      assessment of salivary gland tumors can be achieved. Diffusion-weighted magnetic
      resonance imaging (MRI) is a new imaging tool and the power of distinction of
      pleomorphic adenoma from malignant tumors is promising. The use of botulinum
      toxin for salivary glands diseases is increasing. Intraglandular injections have
      been shown to induce salivary gland atrophy in animal experiments. The
      availability of biologicals is currently yielding new aspects for the treatment
      of Sjogren's disease.

PMID- 19756612
TI  - [Minutes of the meeting of the Dermatopathology Working Group].

PMID- 19756613
TI  - [Report of the oral pathology working group].

PMID- 19756614
TI  - [Inflammatory fibroid polyps are true neoplasms with PDGFRA mutations].
AB  - AIMS: Inflammatory fibroid polyps (IFP) are proliferations of CD34-positive
      spindle cells in the submucosa and mucosa of the gastrointestinal tract with an
      inflammatory infiltrate. IFP occur in the stomach, small bowel, colon and
      esophagus. To date, etiology and pathogenesis are unclear. METHODS: A total of 29
      IFP originating in the stomach, small bowel and colon were examined
      immunohistochemically, and mutational analyses of PDGFRA exons 10, 12, 14 and 18
      were conducted. RESULTS: Activating mutations in PDGFRA exons 12 and 18 were
      found in 20 cases (69%). The mutational types are related to mutations known from
      gastrointestinal stromal tumors (GIST). D842V was the most frequent mutation. No
      activating mutations were found in exons 10 and 14. CONCLUSIONS: The majority of
      IFP reveal activating PDGFRA mutations. Our data indicate that IFP are true
      neoplasms (true benign tumors) and not reactive lesions. In terms of
      pathogenesis, the relationship between PDGFRA-mutant GISTs and IFP remains to be
      determined.

PMID- 19756615
TI  - [Comparing immunohistochemical diagnosis of cancer of unknown primary with gene
      expression-based tumor classification].
AB  - Five percent of cancer cases present as metastases. If the primary tumor cannot
      be identified after diagnostic workup, the disease is referred to as cancer of
      unknown primary (CUP) and is classified as C80.9 according to ICD-10. In Germany,
      CUP is among the ten most common causes of tumor-related death, with mortality
      similar to mortality in gastric or pancreatic cancer. Biopsies of the tumor
      manifestation are generally examined histopathologically and by
      immunohistochemistry (IHC). Gene expression profiling (GEP) is a new diagnostic
      technique that might further contribute to tumor specification.In a retrospective
      study, 43 CUP cases underwent central immunohistochemical review and centrally
      performed GEP using a classifier based on 495 genes. There was concordance
      between IHC, GEP and clinical picture in 54% of cases. In four cases, the
      combination of methods led to an unequivocal identification of the primary
      tumor.In conclusion, we regard detailed IHC workup and complementary GEP
      advisable for the purposes of targeted therapy, as well as to identify or exclude
      specific tumors in a CUP situation.

PMID- 19756616
TI  - [Cervical cancer screening: past--present--future].
AB  - Despite the undisputed and impressive success which has been achieved since the
      1960s by cervical cytology in the fight against cervical cancer and its precursor
      stages, during which the mortality rate in industrialized countries over the last
      40 years has been reduced by two-thirds to three-quarters, a perfect and error
      free screening procedure is still a long way off and will probably never be
      reached. There are two main reasons for this, the lack of adequate coverage and
      suboptimal quality and assessment of smears. Two screening procedures are in use
      Europe, an opportunistic and an organized system. Both systems have many
      advantages but also disadvantages. In organized programs the coverage is higher
      (up to 80%), although similar numbers are also achieved by non-organized programs
      over a 3-year cycle, even if they cannot be so exactly documented. The decision
      on which system is used depends on the health system of the country, public or
      non-public, and many other national circumstances. However, in both systems
      prerequisites for a satisfactory result is a high quality in the sampling
      technique, the processing and the assessment. Therefore, several guidelines have
      been introduced by state and medical societies for internal and external quality
      assurance. New technologies, such as thin-layer cytology or automation for
      replacement or support of conventional cytology liquid-based cytology proved not
      to be superior enough to justify the high costs of these systems. The recognition
      of the strong causal relationship between persistent infection with high-risk
      human papillomavirus (HPV) types and cervical cancer and its precursors has
      resulted in the development of comparably simple tests. Primary screening using
      HPV typing alone is not recommended in opportunistic screening due to the low
      specificity but high sensitivity because it leads to many clinically irrelevant
      results which place women under stress. In organized screening HPV testing is
      always and only possible in combination with cytology. Various models and
      approaches are in the testing phase and appear promising. HPV testing is on the
      other hand well accepted and recommended as a triage test to select women with
      equivocal smear results (Pap group III, ASCUS) if a biopsy is required or can be
      followed up and also for follow-up of patients after cone biopsy. However,
      vaccination of young girls against oncogenic HPV types which has now become
      widespread still leaves many questions open for the future because the
      observation period is too short. There is justified hope that this will become a
      valuable tool in cervical cancer control and may lead to a substantial reduction
      in the burden of cervical cancer in the future. However, as the current vaccines
      on the market do not cover all oncogenic virus types and the effects of
      vaccination will only be observed after many years, the necessity of a
      cytological screening will remain unrestricted. Therefore, cervical cytology will
      remain as the trusted, simple to use, economic and proven, like no other method
      for early cancer detection, efficient procedure even in the foreseeable future.
      If carried out with the highest quality demands it will play a central role in
      the early detection of cervical cancer.

PMID- 19756617
TI  - [Opening speech by the conference president of the German Pathology Society].

PMID- 19756619
TI  - [MALDI imaging mass spectrometry for direct tissue analysis].
AB  - Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry is
      a new method for investigating the distribution of proteins and small molecules
      within biological systems through the in situ analysis of tissue sections using
      MALDI-TOF (time-of-flight) mass spectometry. The power of this technology lies in
      its capability to reliably combine protein data with specific cellular regions
      within the tissue. For the molecular image analysis, tissue samples are measured
      in a raster-like process in the mass spectrometer and for each spot a mass
      spectrum is obtained from molecules within the irradiated area. Software tools
      generate a mass spectrometry image or molecular weight-specific map of the sample
      at any desired molecular weight value and the presence and location of proteins
      and peptides are visualized in the tissue.There are three main fields of
      application, comprising molecular histology, screening for new biomarkers, and
      detection of drugs and their metabolites directly in the tissue.

PMID- 19756620
TI  - [Immunocytochemical identification of carcinomas of unknown primaries on fine
      needle-aspiration-biopsies].
AB  - Clinical investigations with imaging- and endoscopic techniques in order to
      identify the primary tumor sites in patients with CUP syndrome generally entail a
      significant diagnostic effort. If costs exceed <euro> 800.00, a financial loss
      ensues for German hospitals, as public health insurance companies do not
      reimburse above this amount. Combined cytological/immunocytochemical
      investigation of metastatic cancer cells represents a cost-effective, minimally
      invasive procedure to identify the probable primary cancer site that can be
      applied on an outpatient basis. We report on 85 fine needle aspiration biopsies
      of metastases to the liver, 30 to the lymph nodes and over 180 serous effusions
      and/or ascites with metastatic cancer cells in CUP. After conventional
      microscopic inspection, a routine panel of six monoclonal antibodies was applied
      (CK 5/6, CK 7, CK 20, Cdx 2, TTF 1 and CA 125). We were thus able to correctly
      identify the primary tumor sites in 90.3%, 92.0% and 85.1%, respectively, within
      three days. In total, 23 primary hepatocellular carcinomas could all be
      classified correctly, applying the antibodies HepPar 1, BerEp 4, AFP, CD 31, CD
      68 and Ki 67. In addition, 141 malignant epithelial mesotheliomas were typed
      correctly in 97.1%, using the antibodies BerEp 4, Calretinin, Mesothelin, EMA and
      WT. Therefore, immunocytochemical investigation of metastatic cancer cells from
      fine needle aspiration biopsies or in serous effusions offers an efficient, cost
      effective diagnostic alternative to imaging and endoscopic techniques in the
      workup of patients with CUP syndrome.

PMID- 19756621
TI  - [Update on immunohistological classification of amyloidoses].
AB  - The exact classification of amyloid in surgical pathology specimens is
      complicated by the increasing number of amyloid diseases, with more than 25
      different currently known amyloid proteins. Special attention has to be paid to
      distinguishing hereditary amyloidosis from AL amyloidosis. For this reason we
      started several years ago to search specifically for hereditary amyloidoses by
      improving the immunohistochemical classification of amyloid with new antibodies
      and by applying molecular biology. Since then we have found various cases of
      systemic and local amyloid diseases in Germany, including, AApoAI-, AFib-, AKer-,
      ALys- and ATTR-amyloidosis, as well as hitherto unknown amyloidoses. Based on an
      increasing number of referrals we also collected substantial numbers of cases,
      which allowed a direct comparison of the prevalences of the various amyloid
      diseases in organ biopsies.

PMID- 19756622
TI  - [Amyloid centers in Europe: the EURAMY project].
AB  - The systemic amyloidoses comprise a large group of serious protein deposition
      diseases. Although rather rare, the disorders are spread all over the world.
      Increasing understanding of pathogenic mechanisms and recent hope for treatment
      options demand further research and development of diagnostic procedures. The
      European Union Framework 6 program EURAMY (http://www.EURAMY.org) is devoted to
      all aspects of research on systemic amyloidoses, from molecular aspects to
      treatment of patients.

PMID- 19756624
TI  - [Minutes of the meeting of the Working Group on Uropathology: on the occassion of
      the 93rd Annual Conference of the German Society of Pathology in Freiburg].

PMID- 19756623
TI  - [Apoptosis resistance in malignant tumors: novel apoptosis-based therapeutic
      approaches].
AB  - Numerous data indicate that defects in apoptotic signaling pathways contribute to
      the development of cancer and to therapy resistance in many types of malignant
      tumors. Defective apoptotic cell death is not only a significant cause of cancer,
      but also increases tumor resistance to chemo- and radiotherapy. Therefore, there
      is an urgent need to elucidate the molecular basis of apoptosis resistance and to
      develop novel strategies to overcome this resistance. One important task is the
      identification of those anti-apoptotic proteins that render tumor cells resistant
      to therapy and to investigate how these resistance mechanisms can be regulated on
      a cellular and molecular level. Based on these findings, novel strategies to
      sensitize cancer cells to cell death induction can be developed. Moreover, the
      expression profiles of several apoptosis-regulating proteins can be used as
      prognostic factors in patients with diverse types of cancer.

PMID- 19756625
TI  - [Minutes of the meeting of the German Society of Pathology's Working Group on
      Information Technology: Freiburg, 04.06.2009].

PMID- 19756627
TI  - The complete mitochondrial genome sequence of the liverwort Pleurozia purpurea
      reveals extremely conservative mitochondrial genome evolution in liverworts.
AB  - Plant mitochondrial genomes have been known to be highly unusual in their large
      sizes, frequent intra-genomic rearrangement, and generally conservative sequence
      evolution. Recent studies show that in early land plants the mitochondrial
      genomes exhibit a mixed mode of conservative yet dynamic evolution. Here, we
      report the completely sequenced mitochondrial genome from the liverwort Pleurozia
      purpurea. The circular genome has a size of 168,526 base pairs, containing 43
      protein-coding genes, 3 rRNA genes, 25 tRNA genes, and 31 group I or II introns.
      It differs from the Marchantia polymorpha mitochondrial genome, the only other
      liverwort chondriome that has been sequenced, in lacking two genes (trnRucg and
      trnTggu) and one intron (rrn18i1065gII). The two genomes have identical gene
      orders and highly similar sequences in exons, introns, and intergenic spacers.
      Finally, a comparative analysis of duplicated trnRucu and other trnR genes from
      the two liverworts and several other organisms identified the recent lateral
      origin of trnRucg in Marchantia mtDNA through modification of a duplicated
      trnRucu. This study shows that the mitochondrial genomes evolve extremely slowly
      in liverworts, the earliest-diverging lineage of extant land plants, in stark
      contrast to what is known of highly dynamic evolution of mitochondrial genomes in
      seed plants.

PMID- 19756628
TI  - FgEnd1 is a putative component of the endocytic machinery and mediates
      ferrichrome uptake in F. graminearum.
AB  - The function of endocytic pathway in filamentous fungi has remained elusive.
      Recently, we have identified that FgEnd1, which has a 27% amino acid homology and
      shares specific EH3 domain with ScEnd3 of Saccharomyces cerevisiae, is a putative
      member of the endocytic machinery in Fusarium graminearum. The failure of the
      scend3 mutant to uptake Lucifer yellow (LY) was recovered by introducing FgEnd1
      into S. cerevisiae. The deletion of fgend1 in F. graminearum resulted in a 2-fold
      decrease in the rate of uptake of the endocytic marker FM4-64 when compared to
      wild-type cells. The rate of uptake was similar to that seen in latrunculin A
      (Lat-A)-treated cells. Furthermore, fgend1 deletion strain of F. graminearum
      showed lower ferrichrome (FC) uptake activity than wild-type F. graminearum, and
      the same rate as LatA-treated cells. Taken together, these results suggest that
      FgEnd1 is a putative member of the endocytic machinery, although it acts through
      a different mechanism from ScEnd3 or ScEnd4 of S. cerevisiae.

PMID- 19756629
TI  - Identification of transcribed and persistent variants of the psbA gene carried by
      plastid minicircles in a dinoflagellate.
AB  - Plastid genomes of the peridinin-containing dinoflagellates are composed of a
      limited number of genes that are contained separately on small circular molecules
      (minicircles). It has been shown that occasionally aberrant minicircles are
      generated, but they are usually small and contain little coding information. In
      this study, we discovered multiple variants, a putative "gene family", of the
      gene psbA in the plastid minicircles of the dinoflagellate Alexandrium tamarense,
      which have persisted for almost 3 years in culture. Each variant, like the
      ordinary psbA, existed on distinct minicircles of similar size (5-6 kb). These
      psbA variants retained all, or almost all, the coding sequence of the ordinary
      gene, and all four were transcribed and edited after transcription, even though
      they could not encode the entire protein due to intervening or translocated
      sequences. Repeat elements were generally found in the relatively large non
      coding region of these minicircles. Each psbA variant might have been generated
      by DNA recombination and/or replication slippage, as for previously reported
      aberrant minicircles. The fact that these minicircles are transcribed,
      individually edited and maintained in the genome suggests that they are
      functionally important, although their precise roles remain unclear.

PMID- 19756630
TI  - A COL2A1 gene polymorphism is related with advanced stages of osteoarthritis of
      the knee in Mexican Mestizo population.
AB  - Primary osteoarthritis (OA) is a multifactorial disease with several genetics
      factors involved. The COL2A1 gene is of particular interest because it encodes
      for the most abundant protein in articular cartilage. The aim was to evaluate the
      association of COL2A1 gene polymorphism with OA of the knee in Mexican Mestizo
      patients. A case-control study was conducted; cases comprised patients with a
      radiologic scoring > or = 2 and controls with a radiologic scoring <2. DNA was
      extracted from a peripheral blood sample, the polymorphic site of the COL2A1 gene
      was submitted to polymerase chain reaction (PCR), and the products were digested
      using PvuII restriction enzyme. For statistical analysis, a non-conditional
      logistic regression was developed. There were no associations among alleles in
      the overall sample, nevertheless, a significant association was found with p
      (Pp/pp) allele and OA of the knee grade 4 [odds ratio (OR), 95% confidence
      interval (CI 95%) 4.1 (1.2-14.6)] adjusted by gender, age, and body mass index
      (BMI). These results suggest an association of a COL2A1 gene polymorphism with
      advanced stages of OA of the knee in Mexican Mestizo population.

PMID- 19756631
TI  - The promoter of a gene encoding an isoflavone reductase-like protein in coffee
      (Coffea arabica) drives a stress-responsive expression in leaves.
AB  - A cDNA clone (designated CaIRL) encoding an isoflavone reductase-like protein
      from coffee (Coffea arabica) was retrieved during a search for genes showing
      organ/tissue-specific expression among the expressed sequence tags (EST) of the
      Brazilian coffee EST database. The CaIRL cDNA contains a single open reading
      frame of 946 nucleotides (nt) encoding 314 amino acids (predicted molecular
      weight of 34 kDa). Several features identified the predicted CaIRL protein as a
      new member of the PIP family of NADPH-dependent reductases. Expression studies
      demonstrated that CaIRL is expressed exclusively in coffee leaves and its
      transcript level is markedly increased in response to fungal infection and
      mechanical injury. Analysis of transgenic tobacco plants harboring a CaIRL 5'
      flanking region (862 nt) fused to uidA reporter gene (GUS) confirmed the
      responsiveness of the putative promoter to abiotic stress in wounded leaves. In
      turn, a 5' deletion to -404 completely abolished promoter activation by abiotic
      stimulus in transgenic plants. The lack of GUS expression in non-wounded leaf
      tissues in transgenic tobacco was in contrast to the basal level of CaIRL
      expression observed in non-stressed healthy coffee leaves.

PMID- 19756632
TI  - Accelerated stem cell labeling with ferucarbotran and protamine.
AB  - OBJECTIVE: To develop and characterize a clinically applicable, fast and
      efficient method for stem cell labeling with ferucarbotran and protamine for
      depiction with clinical MRI. METHODS: The hydrodynamic diameter, zeta potential
      and relaxivities of ferucarbotran and varying concentrations of protamine were
      measured. Once the optimized ratio was found, human mesenchymal stem cells (MSCs)
      were labeled at varying incubation times (1-24 h). Viability was assessed via
      Trypan blue exclusion testing. 150,000 labeled cells in Ficoll solution were
      imaged with T1-, T2- and T2*-weighted sequences at 3 T, and relaxation rates were
      calculated. RESULTS: Varying the concentrations of protamine allows for easy
      modification of the physicochemical properties. Simple incubation with
      ferucarbotran alone resulted in efficient labeling after 24 h of incubation while
      assisted labeling with protamine resulted in similar results after only 1 h. Cell
      viability remained unaffected. R2 and R2* relaxation rates were drastically
      increased. Electron microscopy confirmed intracellular iron oxide uptake in
      lysosomes. Relaxation times correlated with results from ICP-AES. CONCLUSION: Our
      results show internalization of ferucarbotran can be accelerated in MSCs with
      protamine, an approved heparin antagonist and potentially clinically applicable
      uptake-enhancing agent.

PMID- 19756633
TI  - Considerations on prostate cancer: diagnosis and treatment  decisions.

PMID- 19756634
TI  - Laser fragmentation of foreign bodies in the urinary tract: an in vitro study and
      clinical application.
AB  - PURPOSE: Foreign bodies of the urinary tract represent a urologic emergency.
      First-line treatment is endoscopic removal, but this is often impeded by
      restricted space, especially in the urethra. We postulated that foreign objects
      could be fragmented by Holmium:YAG laser and investigated its effect on objects
      of varying composition. METHODS: In a specially designed stage flushed with
      physiologic saline, medical and non-medical objects of differing composition and
      diameter were subjected to fragmentation by Holmium:YAG at powers of 18 and 30 W.
      In additional thermal experiments, 5,000 J was applied to differing volumes of
      0.9% sodium chloride. Experiments were repeated ten times. RESULTS: With one
      exception (16 Ch silicon catheter) all medical objects were fragmented (latex
      urinary catheter, ureteral stents, and guidewires). Of non-medical objects (wood,
      steel, copper, graphite, and nylon) only copper wire was not amenable to laser
      dissection. These in vitro results were applied in two patients who presented
      with a pencil (wood and graphite) in the urethra or bladder. After Holmium:YAG
      laser fragmentation, the pencil could be removed by forceps each. CONCLUSION:
      Foreign objects in the urinary tract can be fragmented with a Holmium:YAG laser.
      When foreign bodies are too big for initial endoscopic extraction, the clinician
      should consider this technique as a reasonable and atraumatic option to avoid
      open surgery.

PMID- 19756635
TI  - [Acute angle closure glaucoma with unilateral acute loss of vision].
AB  - We report the case of a 31-year-old patient who presented with unilateral acute
      loss of vision, severe headache, and symptoms of an acute angle-closure glaucoma.
      Surprisingly, a prepapillary uveal melanoma was the underlying reason; that is, a
      masquerade syndrome was seen. Enucleation and histopathological investigation of
      that eye were performed within 3 days after first presentation. Acute angle
      closure glaucoma as the initial presentation of uveal melanoma is rare.
      Nevertheless, clinicians should be aware that patients with refractory unilateral
      angle-closure glaucoma and asymmetrically opaque media may harbor an occult uveal
      melanoma.

PMID- 19756636
TI  - [Intracameral moxifloxacin: a safe option for endophthalmitis prophylaxis? In
      vitro safety profile for intraocular application].
AB  - BACKGROUND: Moxifloxacin (Vigamox), a 4th-generation fluoroquinolone, covers most
      isolates causing endophthalmitis. It is safe and effective for systemic and
      topical use; however, only very limited data are available on prophylactic
      intracameral administration to prevent endophthalmitis. This study investigated
      the safety of Vigamox for intracameral application in a cell-culture model.
      METHODS: The endothelial toxicity of moxifloxacin (Vigamox) was evaluated in
      cultured human corneas. Primary human retinal pigment epithelium cells (RPEs),
      trabecular meshwork cells (TMCs), lens epithelium cells (LECs), and corneal
      endothelial cells (CECs) were treated with concentrations of Vigamox. Toxic
      effects were evaluated after 24 h (MTT assay and live-dead assay). By treating
      TMC, CEC, and RPE cells either with oxidative stress or tumor necrosis factor
      alpha (TNF-a), lipopolysaccharide (LPS), and interleukin-6 (IL-6), the effects of
      moxifloxacin on cellular viability under conditions of inflammation were
      investigated. RESULTS: No corneal endothelial toxicity could be detected after 30
      days of treatment with moxifloxacin 500 microg/ml. Primary RPEs, TMCs, LECs, and
      CECs showed adverse effects on proliferation and viability only at concentrations
      higher than 150 microg/ml moxifloxacin. After preincubation with TNF-a, LPS, and
      IL-6 for 24 h and subsequent treatment with moxifloxacin at concentrations of 10
      150 microg/ml for 24 h, no significant decrease in proliferation or viability was
      observed. H2O2 exposure did not increase cellular toxicity CONCLUSION: Vigamox
      did not show significant toxicity on primary RPEs, TMCs, LECs, CECs, or human
      corneal endothelium at concentrations up to 150 microg/ml. The MIC90 of
      moxifloxacin for pathogens commonly encountered in endophthalmitis is known to be
      in the range of 0.25-2.5 microg/ml. Therefore, intracameral use of Vigamox at
      concentrations up to 150 microg/ml may be safe and effective for preventing
      endophthalmitis after intraocular surgery.

PMID- 19756637
TI  - [Subluxation of hydrophilic acrylate intraocular lenses due to massive capsular
      fibrosis].
AB  - BACKGROUND: Compared with other biomaterials, hydrophilic acrylate provides
      better uveal biocompatibility, lower adhesion rates of bacteria and silicone oil,
      and less glare. Because of reduced capsular biocompatibility, increased fibrosis
      may initiate dislocation of the intraocular lens (IOL). PATIENTS: In six eyes of
      four patients, enhanced fibroses led to IOL dislocation, leading to an IOL
      exchange an average of 40 weeks after implantation of the same hydrophilic
      acrylate lens type. DISCUSSION: Predisposing factors were found in 90% of all
      reported cases of IOL dislocation in the literature, but not in the cases
      described here. The lens type that was implanted was unable to adapt to the
      massive fibrosis induced by its hydrophilic biomaterial. CONCLUSIONS: The pattern
      of lens opacification should receive attention when one is choosing an IOL type.
      Eyes showing pseudoexfoliation syndrome as well as post-uveitis eyes might
      require a hydrophilic IOL for less cellular reaction, whereas a posterior
      subcapsular cataract might need a hydrophobic IOL to prevent a massive capsular
      fibrosis. In the case of increased capsular contraction, unreflected YAG laser
      capsulotomy may result in IOL subluxation when the lens design cannot handle
      capsule shrinkage, as demonstrated here.

PMID- 19756638
TI  - [Hereditary optic atrophies].
AB  - Hereditary optic neuropathies are caused by mutations either in the nuclear or
      mitochondrial genome and lead to retinal ganglion cell death mediated by reduced
      oxidative phosphorylation, fragmentation of the mitochondrial network, and
      increased sensitivity to apoptosis. Nuclear mutations result in autosomal
      dominant optic atrophy, autosomal recessive optic atrophy, or X-linked recessive
      optic atrophy, whereas mitochondrial mutations result in Leber's hereditary optic
      neuropathy, which is maternally inherited. A tentative diagnosis of a hereditary
      optic neuropathy can usually be made on the grounds of a thorough patient and
      family history, visual field and color vision tests, and a detailed assessment of
      the optic nerve head. The rarity of hereditary optic neuropathies makes it
      difficult to include these disorders in the differential diagnosis. Molecular
      genetic testing of a blood DNA sample should be performed on every patient, with
      implications for future genetic counseling and prediction of the disease course.

PMID- 19756639
TI  - [Retrospective case analysis of ophthalmological and systemic risk factors in
      patients with retinal vascular occlusion].
AB  - OBJECTIVE: The aim was to determine systemic risk factors for acute central
      retinal artery occlusion (CRAO) and central retinal vein occlusion (CRVO) and to
      evaluate the usefulness of systemic diagnostics in CRAO and CRVO. METHODS: The
      study consisted of a retrospective chart review including 80 patients (CRAO 38,
      CRVO 42). All patients underwent systemic diagnostics including blood pressure
      measurement, blood cholesterol level, carotid Doppler imaging, transthoracic
      echocardiography (TTE), intraocular pressure measurement, glaucoma history and
      presence of thrombophilic factors. A systemic medical history was obtained.
      RESULTS: Systemic hypertension was found in 76.3% CRAO and 75.6% CRVO patients.
      Abnormal cardiac findings were detected in 61% (CRAO) and 22% (CRVO). Abnormal
      carotid findings were detected in 44.1% for CRAO and 9.5% for CRVO. Pathological
      thrombophilic factors were found in both groups for approximately 15%.
      CONCLUSIONS: TTE and carotid Doppler are important tools in the diagnosis of
      sources of emboli in patients with CRAO, while for CRVO abnormal findings are
      revealed by TTE and carotid Doppler less often. Thrombophilia should be ruled out
      in the absence of common risk factors, especially in younger patients and
      systemic hypertension should be adequately controlled.

PMID- 19756640
TI  - [Unilateral occlusion of the retinal artery branch and retinal white dots].
AB  - BACKGROUND: Since the 1990s an increase in the incidence of syphilis has been
      observed. The classical course of syphilis can be subdivided into three stages.
      Ocular involvement is particularly possible in stage III. The disease can be
      efficiently treated by antibiotic therapy. METHODS: We report on the case of a 38
      year-old patient who presented with loss of nasal visual field and hazy vision in
      the left eye which had suddenly appeared 2 weeks previously. The patient had
      received an intravitreal injection of triamcinolon 6 weeks prior to this for
      mainly left-sided cystoid macular edema which had been interpreted as the
      manifestation of hypertensive retinopathy by blood pressures of 200/130. RESULTS:
      An arterial branch occlusion temporal superior could be detected
      biomicroscopically as well as multiple sharply defined, whitish-yellow,
      epiretinal and intraretinal spots and lightly blurred papillary edges. Lues
      serology revealed very high titers. After 2 weeks of i.v. penicillin G therapy
      there was a clear regression of the chorioretinal foci but persistence of the
      reduction in vision and loss of visual field. CONCLUSIONS: Because of the
      increasing incidence of syphilis it is becoming more important to consider this
      disease in the differential diagnosis not only for unclear symptom complexes but
      also in apparently obvious situations.

PMID- 19756641
TI  - [Retinal pigment epithelium atrophy and hypacousia in monozygotic twin sisters].
AB  - Mitochondrial A3243G point mutations cause variable pathologic changes in
      different organs. Funduscopy revealed sharply demarcated central areas of atrophy
      of the retinal pigment epithelium (RPE) which corresponded to the visual field
      defects. Fundus autofluorescence was reduced in the areas of RPE atrophy but
      showed granular hyperfluorescence of the adjacent RPE. Heteroplasmic
      mitochondrial mutations may cause variable changes in different organ systems.
      However, the ocular phenotype in the described pair of twins was almost
      identical. Fundus autofluorescence showed little progression of the RPE atrophy.

PMID- 19756642
TI  - [Intensive intracorneal keloid formation in a case of Peters plus syndrome and in
      Peters anomaly with maximum manifestation].
AB  - We present two cases of Peters anomaly (Peters plus syndrome and a maximum
      manifestation variant) with abnormally thickened cornea and corneal staphyloma.
      Both patients presented to our hospital shortly after birth and were treated with
      perforating keratoplasty and lensectomy. Histological analysis showed marked
      thickening of the corneal stroma due to abnormal stromal connective tissue
      deposition. Additionally, both eyes showed the characteristic changes of Peters
      anomaly with corneal opacity, adherence of the iris stroma and anterior lens
      surface to the posterior corneal surface, absence of the corneal endothelium,
      Descemet and Bowmans layers. Peters anomaly with abnormally thick intracorneal
      fibrosis with or without congenital corneal staphyloma is a very rare
      manifestation.

PMID- 19756643
TI  - ["Lacteocrumenasia"--Capsular block syndrome III].
AB  - Capsular block syndrome (CBS) is a complication of uncomplicated cataract
      surgery. Depending on etiology and the time of onset CBS can be subdivide into
      three types. The cases of 4 patients with CBS type III who presented with a milky
      fluid in the space between the posterior surface of the implanted intraocular
      lens (IOL) and the anterior surface of the distended posterior capsular bag are
      described. All patients complained of reduced vision. The therapy of choice is
      Nd:YAG laser posterior capsulotomy but with suspected low-grade endophthalmitis
      surgical intervention can also be carried out and submitting the plug for
      bacterial culture.

PMID- 19756644
TI  - [Acanthamoeba keratitis in patients with contact lens wear in the Department of
      Ophthalmology in Debrecen].
AB  - BACKGROUND: With increasing numbers of contact lens wearers, Acanthamoeba
      infections are also more frequent all over the world and also in Hungary. Despite
      improved diagnostic and therapeutic possibilities it can still cause serious
      visual loss. In this study the symptoms, signs, diagnostics and treatment options
      for Acanthamoeba keratitis (AK) in patients treated in our department are
      presented and compared to the literature. PATIENTS AND METHODS: Between 2001 and
      2006 a total of 11 patients were treated in our department for Acanthamoeba
      keratitis. RESULTS: The mean age of the patients was 30 years and the 8 female
      and 3 male patients were all contact lens wearers. In six cases the right eye was
      affected and in five cases the left eye. Poor and improper contact lens hygiene
      was the cause of infection in all cases and 82% of the infections occurred in the
      summer period between June and September. In addition to long-term conservative
      treatment, perforating keratoplasty was performed in six cases. After the therapy
      the best visual acuity was 0.6, but 4 of the patients had a serious visual loss.
      Follow-up time ranged from 6 months to 5 years. CONCLUSIONS: Early diagnosis and
      long-term suitable local therapy are necessary for effective recovery. If the
      patient wears contact lens and there is severe pain with ring infiltration in the
      cornea, Acanthamoeba infection should be considered and suitable therapy should
      be given. Immediately performed perforating keratoplasty does not lead to visual
      improvement. Prevention by informing the patients about adequate hygiene and use
      of the cleaning solutions is one of the most important tasks of contact lens
      specialists.

PMID- 19756645
TI  - [Retained Descemet's membrane after penetrating keratoplasty for macular corneal
      dystrophy].
AB  - A 35-year-old woman underwent excimer laser penetrating keratoplasty for macular
      corneal dystrophy in the right eye. Two months after surgery, a thin transparent
      membrane behind the clear corneal graft was noted. Anterior segment optical
      coherence tomography revealed duplication of the anterior chamber by this
      membrane, originating from the host cornea without direct contact to the donor
      tissue. Trypan-blue-assisted descemetorhexis was performed, and histopathology
      confirmed the diagnosis of retained Descemet's membrane. Four months later, the
      graft was clear with good visual acuity and no sign of retrocorneal membrane.

PMID- 19756646
TI  - [Continuous intraocular pressure measurement: First results with a pressure
      sensitive contact lens].
AB  - BACKGROUND: A prototype of a pressure-sensitive contact lens (CL-DCT) based on
      dynamic contour tonometry (DCT) has been developed for continuous intraocular
      pressure (IOP) monitoring. The purpose of the present study was to assess the
      clinical applicability of this CL-DCT. MATERIAL AND METHODS: In 24 healthy
      subjects continuous IOP recording with the CL-DCT for 100 s was accomplished
      including IOP monitoring during 2 consecutive Valsalva manoeuvres. The
      measurement procedure was repeated after 5 min on the same eye and compared with
      the initial measurement. RESULTS: Continuous pressure curves were recorded in 20
      subjects. The CL-DCT revealed an individual increase in IOP from 0.74 to 8.26
      mmHg during the Valsalva manoeuvres. Comparison of the 2 consecutive IOP
      measurements yielded a mean deviation of +/-0.4 mmHg. CONCLUSIONS: CL-DCT allows
      non-invasive and continuous measurements of IOP. The measured values are
      comparable to the expected ones. Further studies are necessary to compare the
      measurement accuracy of CL-DCT with that of slit lamp adapted DCT (SL-DCT).

PMID- 19756647
TI  - Habitat light and dewlap color diversity in four species of Puerto Rican anoline
      lizards.
AB  - Closely related species often have signals that differ dramatically in design.
      The evolution of such differences may be important in the process of speciation.
      Selection for signal detectability under different habitat conditions has been
      proposed as a mechanism leading to the evolution of signal diversity. We examined
      dewlap color in four closely related species of Anolis lizards that occupy
      habitats with different light conditions. Initially, we tested the hypothesis
      that lizards choose specific light conditions within each habitat in which to
      signal. We rejected this hypothesis for all four species. We next calculated the
      detectability of the dewlap color of all four species at display locations in
      each habitat. If selection for detectability under the different light conditions
      explained the divergence in signal design, the occupant of a given habitat was
      predicted to have the highest signal detectability in that habitat. However, the
      rank order of detectability of the four dewlap colors was nearly the same in all
      four habitats. We concluded that divergent selection for signal detectability
      does not, by itself, explain the evolution of dewlap color diversity. We
      hypothesize that the evolution of dewlap color diversity results from
      simultaneous selection for multiple functions of dewlap color.

PMID- 19756648
TI  - Comparing inclined locomotion in a ground-living and a climbing ant species:
      sagittal plane kinematics.
AB  - Formicine ants are able to detect slopes in the substrates they crawl on. It was
      assumed that hair fields between the main segments of the body and between the
      proximal leg segments contribute to graviception which triggers a change of
      posture in response to substrate slopes. The sagittal kinematics of two ant
      species were investigated and compared on different slopes. Cataglyphis fortis, a
      North African desert ant, is well known for its extraordinary sense of
      orientation in texturally almost uniform habitats, while Formica pratensis, a
      common central-European species, primarily uses landmarks and pheromone traces
      for orientation. A comparison of these two species reveals differences in
      postural adaptations during inclined locomotion. Only minor slope-dependent
      angular adjustments were observed. The largest is a 25 degrees head rotation for
      Cataglyphis, even if the slope is changed by 150 degrees, suggesting dramatic
      changes in the field of vision. The trunk's pitch adjustment towards the
      increasing slope is low in both species. On all slopes Cataglyphis achieves
      higher running speeds than Formica and displays greater slope-dependent variation
      in body height. This indicates different strategies for coping with changing
      slopes. These specific aspects have to be reflected in the ants' respective mode
      of slope perception.

PMID- 19756649
TI  - Walking in Fourier's space: algorithms for the computation of periodicities in
      song patterns by the cricket Gryllus bimaculatus.
AB  - Is discrimination of the envelope of an acoustic signal based on spectral or
      temporal computations? To investigate this question for the cricket Gryllus
      bimaculatus, pattern envelopes were constructed by the addition of several sine
      waves and modified by systematic phase changes. The phonotactic response of
      female crickets towards such sinusoidal but also rectangular pulse patterns was
      quantified on a locomotion compensator. Envelope patterns that exhibited a
      modulation frequency of 25 Hz as the dominant frequency were attractive and
      although changes of phase modified the temporal pattern, the values of
      attractiveness remained unaffected. Removal of the 25-Hz component reduced the
      phonotactic scores. Patterns in which other frequency components exhibited a
      larger amplitude than the 25-Hz component were less attractive. However, the
      combination of an unattractive pulse period with the attractive modulation
      frequency of 25 Hz in a pattern revealed that such stimuli were unattractive
      despite the presence of the 25-Hz component. A comparison of the attractiveness
      of all patterns revealed that female crickets evaluated the duration of pulse
      period over a wide range of duty cycles. The combined evidence showed that
      pattern envelopes were processed in the time- and not in the spectral domain.

PMID- 19756650
TI  - Behaviorally measured audiograms and gap detection thresholds in CBA/CaJ mice.
AB  - Tone detection and temporal gap detection thresholds were determined in CBA/CaJ
      mice using a Go/No-go procedure and the psychophysical method of constant
      stimuli. In the first experiment, audiograms were constructed for five CBA/CaJ
      mice. Thresholds were obtained for eight pure tones ranging in frequency from 1
      to 42 kHz. Audiograms showed peak sensitivity between 8 and 24 kHz, with higher
      thresholds at lower and higher frequencies. In the second experiment, thresholds
      for gap detection in broadband and narrowband noise bursts were measured at
      several sensation levels. For broadband noise, gap thresholds were between 1 and
      2 ms, except at very low sensation levels, where thresholds increased
      significantly. Gap thresholds also increased significantly for low pass-filtered
      noise bursts with a cutoff frequency below 18 kHz. Our experiments revised
      absolute auditory thresholds in the CBA/CaJ mouse strain and demonstrated
      excellent gap detection ability in the mouse. These results add to the baseline
      behavioral data from normal-hearing mice which have become increasingly important
      for assessing auditory abilities in genetically altered mice.

PMID- 19756651
TI  - Seasonal torpor and normothermic energy metabolism in the Eastern chipmunk
      (Tamias striatus).
AB  - To assess the changes in thermoregulatory characteristics that accompany the
      seasonal expression of torpor we measured seasonal differences in body mass
      adjustments, body temperature (T (b)) and metabolic rate (MR) in both summer- and
      winter-acclimated individuals from a species of food-storing hibernator, the
      Eastern chipmunk (Tamias striatus). Torpor occurred only in the winter and was
      associated with lower normothermic T (b), during inter-bout arousal periods than
      in the summer. Chipmunks increased body mass before the initiation of torpor in
      winter, and steadily lost mass as the hibernation season progressed. Torpor
      expression was correlated to initial mass gain, with the individuals who showed
      the largest mass increase in the fall showing the highest degree of torpor.
      Acclimation to winter-like conditions produced a decline in normothermic MR at
      all ambient temperatures examined. The findings indicate that torpor expression
      is accompanied by a decrease in T (b) and MR during normothermy, indicating that
      a conservation of energy metabolism occurs, not only in torpor, but also during
      the inter-bout arousal periods.

PMID- 19756652
TI  - Cupiennius salei: biomechanical properties of the tibia-metatarsus joint and its
      flexing muscles.
AB  - Hunting spiders are well adapted to fast locomotion. Space saving hydraulic leg
      extension enables leg segments, which consist almost soley of flexor muscles. As
      a result, the muscle cross sectional area is high despite slender legs.
      Considering these morphological features in context with the spider's segmented C
      shaped legs, these specifics might influence the spider's muscle properties.
      Moreover, these properties have to be known for modeling of spider locomotion.
      Cupiennius salei (n = 5) were fixed in a metal frame allowing exclusive flexion
      of the tibia-metatarsus joint of the second leg (counted from anterior). Its
      flexing muscles were stimulated supramaximally using needle electrodes.
      Accounting for the joint geometry, the force-length and the force-velocity
      relationships were determined. The spider muscles produce 0.07 N cm maximum
      isometric moment (corresponding to 25 N/cm(2) maximum stress) at 160 degrees
      tibia-metatarsus joint angle. When overextended to the dorsal limit at
      approximately 200 degrees , the maximum isometric moments decrease to 72%, and,
      when flexed to the ventral hinge stop at 85 degrees , they drop to 11%. The force
      velocity relation shows the typical hyperbolic shape. The mean maximum shortening
      velocity is 5.7 optimum muscle lengths per second and the mean curvature (a/F
      (iso)) of the Hill-function is 0.34. The spider muscle's properties which were
      determined are similar to those of other species acting as motors during
      locomotion (working range, curvature of Hill hyperbola, peak power at the
      preferred speeds), but they are relatively slow. In conjunction with the low
      mechanical advantage (muscle lever/load arm), the arrangement of three
      considerably actuated joints in series may nonetheless enable high locomotion
      velocities.

PMID- 19756653
TI  - Antiapoptotic and neuroprotective effects of mycophenolate   mofetil after acute
      spinal cord injury in young rats.
AB  - INTRODUCTION: The aim of this study was to investigate the possible beneficial
      effects of mycophenolate mofetil in comparison with methylprednisolone in an
      experimental model of spinal cord injury in young rats. MATERIALS AND METHODS:
      Young female Wistar albino rats weighing 100-120 g were used in this study. The
      animals were anesthetized, the paravertebral muscles were dissected to expose
      thoracic spinal nerve 7 (T7)-T11 vertebrae, and the spinal cord was exposed at T8
      T10 levels by laminectomy with the assistance of a surgical microscope. Weight
      drop trauma model was used to perform spinal cord trauma. The animals were
      subjected to an impact of 50 g/cm to the dorsal surface of the spinal cord. The
      animals were divided into six groups, and all the groups include 12 animals.
      Group 1 laminectomy, group 2 laminectomy+ trauma, group 3 was treated with
      mycophenolate mofetil, group 4 was treated with methylprednisolone, group 5 was
      treated with mycophenolate mofetil+methylprednisolone, and group 6 served as a
      vehicle. Immediately after the trauma, 25 mg/kg mycophenolate mofetil (to group 3
      and 5) and 30 mg/kg methylprednisolone (to group 4 and 5) were given in a single
      dose. Biochemical, behavioral, pathological, and immunohistochemical analysis
      were done. RESULTS: Significant decrease in the number of apoptotic cells were
      detected in the lesion zone 24 h after the spinal cord injury with the
      mycophenolate mofetil treatment group. Histologic and functional recovery was
      also significant. CONCLUSION: Our results showed that the administration of
      mycophenolate mofetil on traumatic spinal cord injury decreases apoptosis and
      improves neurologic recovery.

PMID- 19756654
TI  - Long-term complications following operative intervention for intestinal
      malrotation: a 10-year review.
AB  - Intestinal malrotation associated with a volvulus requires immediate surgical
      intervention. The long-term sequelae of Ladd's procedure and its complications
      are not well defined. We designed this study to investigate the long-term
      complications following operative intervention for intestinal malrotation.
      Patients who have undergone a Ladd's procedure for malrotation from January 1999
      till December 2008, from two tertiary centres, were identified using the Hospital
      Inpatient Enquiry system. Charts were analysed to obtain information about mode
      of presentation, method of diagnosis and postoperative outcomes. Patients were
      contacted for follow-up. One hundred and sixty-one patients were identified over
      the 10-year period with a postoperative follow-up time ranging from 2 months to
      10 years. The median age at surgery was 9 days (1 day-12 years); 38 (23%)
      underwent elective Ladd's procedure for malrotation. Thirty-eight patients had
      intraoperative incidental findings of a malrotation during different procedures;
      120 (74.5%) patients were performed as an emergency procedure. Fourteen patients
      (8.7%) developed complications following surgery. Nine patients developed
      adhesive small bowel obstruction, five required operative adhesiolysis having
      failed conservative treatment. There was one case of recurrent volvulus and three
      mortalities in our series. In our experience, looking at 161 patients with a mean
      follow-up of 5 years Ladd's procedure has a low postoperative morbidity and
      remains a vital treatment for malrotation in children.

PMID- 19756656
TI  - The effect on cell growth by Wnt1 RNAi in human neuroblastoma SH-SY5Y cell line.
AB  - PURPOSE: We tested the hypothesis that Wnt signaling pathways are critical to
      neuroblastoma development. Our objective was to explore the novel role that
      Wnt/beta-catenin plays in human neuroblastoma cell line SH-SY5Y, including
      detection of expression of wnt1 and beta-catenin in SH-SY5Y, and the
      morphological and proliferative changes after Wnt1 RNAi in SH-SY5Y. METHODS: PCR,
      Western blot and immunofluorescence technology were used to detect the expression
      of Wnt1 in human neuroblastoma SH-SY5Y cell line. RNAi technology was used to
      knock down the expression of Wnt1in SH-SY5Y. SiRNA targeting Wnt1 was transfected
      into SH-SY5Y cells by Lipofectamine2000. The protein expression of Wnt1 and beta
      catenin were detected by Western blotting 48 h after transfection. The quantity
      and the morphologic changes of the cells were recorded under light microscope.
      The growth curve of SH-SY5Y cells after RNAi transfection was drawn through MTT
      assay. RESULTS: Wnt1 was expressed in human neuroblastoma SH-SY5Y cells. The SH
      SY5Y cell was successfully transfected with siRNA targeting Wnt1 mediated by
      Lipofectamine in vitro. The proteins expression of Wnt1 and beta-catenin
      decreased after transfection with siRNA; the numbers of the cells were decreased,
      accompanying abundant floating and dead cells under the light microscope. SH-SY5Y
      cells transfected with siRNA targeting Wnt1 showed less viability. CONCLUSION:
      Wnt1 and beta-catenin expressed in SH-SY5Y cells. Knockdown of endogenous wnt1
      expression could result in cell death and inhibit cell growth. From our study, we
      suggest that the activated embryonal development-related wnt1/beta-catenin
      pathway might take part in the oncogenesis and growth of neural crest-derived
      neuroblastoma.

PMID- 19756655
TI  - Teratogens inducing congenital abdominal wall defects in animal models.
AB  - Congenital abdominal wall defects are common anomalies which include
      gastroschisis, omphalocele and umbilical cord hernia. Recent reports indicate
      that gastroschisis is increasing in prevalence, whereas omphalocele has remained
      steady, suggesting that environmental factors may play a part in their
      pathogenesis. The aim of this study is to review animal teratogen studies
      resulting in abdominal wall defects to investigate their possible causes. Each
      report was examined not only for the teratogens causing the defects, but also to
      carefully identify the defect occurring and its correlation with the known
      clinical anomalies. We found many discrepancies between the nomenclature used by
      animal teratology investigators and that used by clinicians. We were able to
      confirm the induction of gastroschisis by 22 teratogens, omphalocele by 9
      teratogens and umbilical cord hernia by 8. There is no doubt that environmental
      factors may be responsible, at least in part, for all three of the clinical
      abdominal wall defects. Future studies should take care to appreciate the
      differences between these anomalies and describe them in detail, so that accurate
      and meaningful conclusions can be obtained.

PMID- 19756657
TI  - Prospective evaluation of comorbidity and psychosocial need in children and
      adolescents with anorectal malformation. Part one: paediatric surgical evaluation
      and treatment of defecating disorder.
AB  - INTRODUCTION: Anorectal malformations represent a continuing challenge for the
      paediatric surgeon. Faecal and urinary incontinence can occur even with an
      excellent anatomic repair. We undertook a prospective evaluation of comorbidity
      and psychosocial needs in children and adolescents with anorectal malformation to
      test the hypothesis whether psychosocial workup in concert with an improved
      continence situation would lead to a better functional outcome in patients
      suffering from defecating disorders. Treatment of defecating disorder was based
      on differentiation between overflow pseudo-incontinence and true faecal
      incontinence. MATERIALS AND METHODS: Patients who presented with soiling
      regardless of the type of anomaly were included in the study: 44 patients were
      investigated, 14 patients did not meet the criteria of the study, 30 patients
      aged 4-18 were evaluated. The surgical diagnostic program comprised a careful
      clinical history, physical examination, exact classification of the malformation,
      evaluation for associated defects, stool protocol. RESULTS: Patients were grouped
      in two different management programs according to their continence situation.
      Patients with pseudo-incontinence were treated with enemas, diet, anal hygiene,
      behavioural therapy and physiotherapy. Patients with true faecal incontinence
      were included in a bowel management program: 28 patients were free of symptoms of
      soiling after 3 days of hospital treatment and remained free of symptoms 6 months
      and 1 year later at re-evaluation. Two patients did not follow the therapeutic
      regime and therefore did not show an improved condition concerning soiling in the
      long run. CONCLUSION: Differentiating between overflow pseudo-incontinence and
      true faecal incontinence is the basis of an effective treatment of defecating
      disorders. All patients born with anorectal malformation can be kept clean of
      stool if they are subjected to an adequate treatment. A multidisciplinary
      approach is a valuable supplement to standard therapy.

PMID- 19756658
TI  - Erythropoietin production caused by metastatic colon cancer.

PMID- 19756660
TI  - [Multinational evidence-based recommendations for the use of methotrexate in
      rheumatic disorders with the focus on rheumatoid arthritis. Integration of a
      systematic literature research with the expert opinion of a large international
      panel of rheumatologists within the framework of the 3e initiative].

PMID- 19756659
TI  - [Recommendations on therapy using interleukin-1beta-blocking agents].
AB  - In Germany, the only available interleukin-1beta (IL-1beta) blocking agent is
      anakinra (ANR) (as of August 2009) which is given subcutaneously at a dosage of
      100 mg/day (adults) and 1-2 mg/kg body weight/day (maximum 100 mg/day)
      (children), respectively. Based on published data and clinical experience the
      German Society of Rheumatology (Deutsche Gesellschaft fur Rheumatologie)
      recommends the following indications for ANR: (1) Rheumatoid arthritis, if
      treatment with two DMARDs (one of the two being methotrexate, MTX) for at least 6
      months has failed. (2) Adult-onset and juvenile-onset Still's disease (systemic
      juvenile idiopathic arthritis) in the case of insufficient response to
      glucocorticoids or inadequate long-term dosage, as well as failure of a
      conventional DMARD, usually MTX. For both indications the treatment should be
      supervised and documented by a rheumatologist or paediatric rheumatologist.
      Cryopyrin-associated periodic syndromes (CAPS) are recommended as an additional
      treatment option for IL-1 blocking therapy. The efficacy of the fusion protein
      rilonacept (RIC) and the monoclonal antibody canakinumab in the treatment of CAPS
      has been proven by randomized, placebo-controlled trials. In the US, RIL was
      recently approved by the FDA for the treatment of CAPS under the "Orphan Drug
      Status".

PMID- 19756661
TI  - [EULAR/PreS consensus criteria 2006 for the classification of childhood
      vasculitides].

PMID- 19756662
TI  - [Fred Siguier (1909-1972). A Paris physician who foresaw the significance of
      systemic disease].
AB  - Fred Siguier was one of the first clinicians in Europe to focus on a group of
      rare, little known and etiologically unclear diseases, which at the time were
      termed collagen diseases and are today known as systemic diseases. Siguier
      described not only the individual disease patterns, but also transitional and
      mixed forms and thereby recognised their innate relationship, although the
      immunological background was unknown at that time. More than half a century ago,
      he was convinced that he was dealing with"diseases of the future". His prognosis
      has been confirmed on every level.

PMID- 19756663
TI  - [Inflammatory myopathies].
AB  - Inflammatory myopathies cover infectious, focal and immunogenic myopathies. This
      review focuses on the clinical features, diagnostic techniques, pathogenesis and
      therapy of immunogenic myopathies. Besides myositis associated with other
      autoimmune disorders, dermatomyositis is the most common immunogenic myopathy.
      The independent diagnosis of polymyositis has come under debate, since within
      this group of patients some are now diagnosed as having either hereditary
      muscular dystrophy with inflammatory signs or inclusion body myositis (IBM). Even
      more strikingly, patients diagnosed with sporadic IBM may now be diagnosed with
      either a form of hereditary IBM or with a form belonging to the group of protein
      aggregate myopathies or myofibrillar myopathies. This re-classification reflects
      the well-known and clinically evident therapeutic dilemma in many of these
      patients. Thus the indication for muscle biopsy or rebiopsy requires new
      consideration and attention.

PMID- 19756664
TI  - [Health-economic assessment of combination therapy for rheumatoid arthritis with
      methotrexat and etanercept based on the TEMPO Study].
AB  - BACKGROUND: The TEMPO study has shown that the combination of etanercept and
      methotrexat (MTX) in the treatment of rheumatoid arthritis (RA) is superior to
      monotherapy. It further suggested that remission of RA is a realistic treatment
      objective. A health-economic assessment of the combination needs to demonstrate
      the suitability of the combination for daily clinical practice taking economic
      aspects into consideration. PATIENTS AND METHODS: For the 686 patients in the
      TEMPO study, a re-analysis was carried out in the form of a Monte-Carlo-Markov
      Chain simulation. Study types were cost-effectiveness analysis and cost-utility
      analysis. Comparators were combined etanercept and MTX vs. MTX alone; the
      perspective was that of society as a whole. RESULTS: The incremental cost
      effectiveness ratio of the combination is <euro>21,300 per life year in remission
      as compared with MTX alone. The incremental cost-utility ratio of the combination
      is <euro>38,700 per quality-adjusted life year. CONCLUSION: Both health-economic
      parameters suggest to adopt the combination therapy into daily clinical practice
      of RA patients.

PMID- 19756665
TI  - [Radiographic healing of sarcoid bone erosion].
AB  - Sarcoidosis is a systemic granulomatous disease that primarily affects the lung
      and other organs. Patients with dactylitis should be screened for abnormalities
      of the skin, eyes and lungs. Even in patients with normal-range ACE sarcoidosis
      could be confirmed by tissue biopsy. Treatment with methotrexate and steroids can
      relieve symptoms and stabilize the disease. In refractory cases leflunomide,
      azathioprine, hydroxychloroquine or antibodies against TNF-alpha can be
      additionally administered.

PMID- 19756666
TI  - [Abstracts of the 37th Congress of the German Society for Rheumatology. September
      23-26, 2009. Cologne, Germany].

PMID- 19756668
TI  - Prenatal stress alters microglial development and distribution in postnatal rat
      brain.
AB  - Stress affects microglial function and viability during adulthood and early
      postnatal life; however, it is unknown whether stress to the pregnant dam might
      alter offspring microglia. The effects of prenatal stress on microglial
      development and distribution in the postnatal brain were studied using Wistar
      rats. Prenatal stress consisting of 20 min of forced swimming occurred on
      embryonic days 10-20. On postnatal days 1 and 10, stressed and control pups were
      killed. Microglia were identified using Griffonia simplicifolia lectin and
      quantified in the whole encephalon. In addition, plasma corticosterone was
      measured in dams at embryonic day 20, and in pups on postnatal days 1 and 10. At
      postnatal day 1, there was an increase in number of ramified microglia in the
      parietal, entorhinal and frontal cortices, septum, basal ganglia, thalamus,
      medulla oblongata and internal capsule in the stressed pups as compared to
      controls, but also there was a reduction of amoeboid microglia and the total
      number of microglia in the corpus callosum. By postnatal day 10, there were no
      differences in the morphologic type or the distribution of microglia between the
      prenatal stress and control groups, except in the corpus callosum; where prenatal
      stress decreased the number of ramified microglia. The stress procedure was
      effective in producing plasma rise in corticosterone levels of pregnant rats at
      embryonic day 20 when compared to same age controls. Prenatal stress reduced the
      number of immature microglia and promoted an accelerated microglial
      differentiation into a ramified form. These findings may be related to an
      increase in plasma corticosterone in the pregnant dam.

PMID- 19756669
TI  - Effective arthroscopic treatment of large, anteriorly extended spinoglenoid
      cysts.
AB  - Despite their rarity, several modalities have been used to treat spinoglenoid
      cysts of the shoulder. Recently, a report was issued on arthroscopic
      decompression through a communication hole and posterior capsulotomy through the
      glenohumeral joint. However, complete cystectomy is not possible using these
      methods if a cyst is large or extends anteriorly. Here, the authors describe a
      method of extra-articular complete cystectomy through the bursal space, which was
      used in three patients with large spinoglenoid cysts that extended anteriorly.
      All three patients were able to return to work without restriction, and in the
      two patients that underwent follow-up MRIs, cysts were completely resolved and
      the infraspinatus muscle mass had partially recovered.

PMID- 19756670
TI  - Comparative survey of pain-alleviating effects between ultrasound-guided
      injection and blind injection of lidocaine alone in patients with painful
      shoulder.
AB  - BACKGROUND: Complaints of shoulder pain are very frequent in clinical practice.
      To relieve this type of pain, intra-subacromial bursa (SAB) injection therapy is
      commonly employed. Injection procedures include blind and ultrasound-guided
      injection. In clinical practice, blind injection is routinely performed. However,
      the SAB is a very thin tissue. Poor response to blind injection may be due to a
      misplaced injection. It is assumed that ultrasound-guided injections are more
      effective than blind injections. The purpose of this study was to compare pain
      alleviating effects between ultrasound-guided injection and blind injection with
      lidocaine alone. MATERIALS AND METHODS: The subjects were 16 patients (20
      shoulders) in whom pain was possibly derived from inflammation of the SAB.
      Initially, ultrasound-guided injection was performed with 2 ml of 1% lidocaine.
      After 1 week, blind injection was conducted in the same patient. They
      subjectively expressed the grade of pain at each time point (before and 1, 5, 10,
      15, 20, 25, and 30 min after injection) as pain scores. We calculated the
      amelioration rate by dividing differences between the scores at each time point
      and before injection by the pre-injection score. RESULTS: Pain scores of
      ultrasound-guided injection were lower than blind injection. Ultrasound-guided
      injection achieved higher mean amelioration rates compared to blind injection,
      showing significant differences at all time points (P < 0.01). CONCLUSIONS:
      Ultrasound-guided technique achieved higher effectiveness compared to blind
      technique.

PMID- 19756671
TI  - Health-related quality of life in patients with an anterior cruciate ligament
      injury.
AB  - INTRODUCTION: We evaluated the quality of life (QOL) in patients with an anterior
      cruciate ligament injury through SF-36 survey, which was a global health-related
      QOL survey, and investigated the correlation of its results with other clinical
      parameters. PATIENTS AND METHODS: Fifty-one patients (mean age 28.7 years) with
      an anterior cruciate ligament injury were studied. Clinical evaluations using SF
      36 version 2 and Lysholm scoring system were conducted, and the ratio of anterior
      tibial translation in affected compared to unaffected knees was obtained.
      RESULTS: In SF-36 survey, scores of both physical and mental health summary
      measures in our subjects were lower than the national standard values. The mean
      ratio of anterior tibial translation was 7.8 +/- 6.0, and no correlation with SF
      36 scores was observed. The mean Lysholm score was 53.3 +/- 17.1; which tended to
      be correlated with the mental health score of SF-36, but not with the physical
      health score. DISCUSSION: Our results clearly demonstrated that patients with an
      anterior cruciate ligament injury had a deterioration of mental health as well as
      physical health.

PMID- 19756672
TI  - The UV response of the skin: a review of the MAPK, NFkappaB and TNFalpha signal
      transduction pathways.
AB  - The sun emits different types of ultraviolet (UV) light. Our skin is a natural
      target of UV radiation which is involved in vitamin D3 production in our body. UV
      radiation at high doses is an environmental carcinogen which can elicit skin
      damage as well as inducing skin cancer. It can mediate inflammatory and
      immunological reactions through activation of receptors, DNA/RNA damage and
      production of reactive oxygen species. It is also involved in the release of pro
      inflammatory cytokines, of which TNFalpha has been implicated in tumorigenic
      activities. In order to mediate its effects, UV radiation is known to activate
      multiple signalling cascades such as the p38 MAPK, Jun N-terminal kinase,
      extracellular signal-regulated kinase 1/2 and NFkappaB pathways in skin cells.
      The role each of these pathways plays in mediating the release of cytokines such
      as TNFalpha remains to be fully characterized. Once the function of these
      pathways is known, this information may provide for the formulation of therapy
      which will prevent the release of immunosuppressive cytokines resulting in a
      reduction in skin cancer formation.

PMID- 19756673
TI  - Effect of lipopolysaccharide, skin sensitizers and irritants on thioredoxin-1
      expression in dendritic cells: relevance of different signalling pathways.
AB  - Thioredoxin-1 is a ubiquitous protein involved in phenotypical and functional
      changes in dendritic cells (DC). We investigated the effect of lipopolysaccharide
      (LPS), skin sensitizers, and irritants on thioredoxin-1 by Western blot and
      immunofluorescence and on mRNA by real-time PCR. As DC models, we used a skin DC
      line and DC derived from human blood monocytes. We observed that all tested
      chemicals increased thioredoxin-1 expression, which is only transient for
      irritants, being the strongest effect observed for LPS (63 +/- 15%). To address
      the involvement of thioredoxin-1 in DC maturation, we analysed the effect of an
      activator of thioredoxin-1 expression, hydrogen peroxide, on CD86 expression, a
      marker of DC maturation. We found that hydrogen peroxide increases thioredoxin-1
      and CD86 expression reinforcing thioredoxin-1 involvement in DC maturation.
      Because mitogen-activated protein kinases and PI3K are activated upon DC
      maturation, we also analysed their involvement in thioredoxin-1 modulation. We
      verified that LPS-induced upregulation of thioredoxin-1 expression was dependent
      on PI3K pathway.

PMID- 19756674
TI  - Prevalence and risk factors of anorectal dysfunction in women with urinary
      incontinence.
AB  - PURPOSE: To evaluate the prevalence and risk factors of anorectal dysfunction
      among women with urinary incontinence. METHOD: This cross-sectional study was
      conducted among women attending the urogynecology clinic. Women with symptoms of
      urinary incontinence were requested to complete a structured questionnaire.
      RESULTS: Four hundred and thirteen women participated in the study and 43.8% had
      at least one anorectal symptom. The prevalence rates of anal incontinence,
      constipation, and difficult defecation were 8.0, 38.0, and 25.7%, respectively.
      The risk factors associated with anorectal dysfunction were age and number of
      parity. CONCLUSION: Anorectal dysfunction was prevalent among women with urinary
      incontinence; age and number of parity were the risk factors. All women with
      symptoms of urinary incontinence should be evaluated about anorectal symptoms.

PMID- 19756675
TI  - The effect of retrieved oocyte count on pregnancy outcomes in an assisted
      reproduction program.
AB  - OBJECTIVE: To determine if women with less than five eggs retrieved do as well as
      women with more eggs retrieved in terms of pregnancy outcomes in our assisted
      reproduction program. METHOD: Two hundred one women undergoing in vitro
      fertilization treatment at Fertility Unit in Royal Prince Alfred Hospital,
      University of Sydney, Australia were selected for retrospective evaluation. The
      women were grouped according to the number of oocytes retrieved at ovum pick-up.
      Group A consisted of women with less than 5 oocytes, group B with 5 to 10 oocytes
      and group C with 11 to 15 oocytes collected. Clinical and ongoing pregnancy rates
      were compared. RESULTS: There was no difference between the groups in terms of
      clinical and ongoing pregnancy rates. CONCLUSION: With good IVF lab conditions,
      if a patient reaches embryo transfer, the number of eggs retrieved should not
      affect the likelihood of pregnancy outcome in an assisted reproductive technology
      treatment.

PMID- 19756676
TI  - Neuroaxial blocks and tattoos: a dilemma?
AB  - PURPOSE: Parturients with lumbar tattoos are often proposed to neuroaxial blocks
      (NB). There are no guidelines for this situation, and no reports of major
      complications derived from NB through tattoos. We conducted a survey of a sample
      of anaesthetists, to find out about their approach when facing NB on parturients
      with lumbar tattoos. METHODS: We surveyed 537 anaesthetists through a multiple
      choice questionnaire. The obtained data were subjected to a descriptive analysis.
      RESULTS: A total of 162 replies were received. Ninety-two anaesthetists had
      already been asked to carry out a NB through a tattoo. Fifty-five of them
      executed the NB on all occasions, always on pigment free skin, 6 always refused
      to do so, and 31 didn't always performed the NB. Most of these approaches were
      based on literature. This is according to the fact that literature is not
      unanimous, which explains opposite actions having similar backgrounds. Of the 70
      anaesthetists never confronted with this situation, 74.3% would carry it out when
      faced with that situation, being that 67.2% would do it over an ink free area,
      while 7.1% would choose the pigmented one. Personal opinion is the major
      grounding for this group. CONCLUSIONS: A tendency towards performing NB on
      pigment free skin, seems to exist. Literature has been the backup for
      anaesthetists confronted with the above scenario, while personal opinion seems to
      have been the basis for the remainders. The nonexistence of guidelines as well as
      the controversy regarding the risks involved in performing NB over tattoo,
      probably explain the diverse actions taken by the anaesthetists.

PMID- 19756677
TI  - Primary bilateral ovarian and uterine Burkitt's lymphoma following chemotherapy
      for breast cancer.
AB  - BACKGROUND: Burkitt's lymphoma is extremely rare in the United States, with
      reports of approximately 300 new cases each year. A case of Burkitt's lymphoma
      involving the uterus, cervix, ovaries and appendix 15 years after adjuvant
      chemotherapy for breast cancer is presented. CASE REPORT: A 58-year-old woman
      presented with an abdominal mass. MRI revealed a pelvic mass originating from the
      uterus. Her past medical history was significant for an infiltrating ductal
      carcinoma of the left breast with positive lymph nodes and extra nodal invasion
      diagnosed at age 43. She had a left modified radical mastectomy in 1990 with
      adjuvant chemotherapy. Histologic sections of the uterus, cervix, ovaries,
      appendix and external iliac lymph node obtained at laparotomy revealed diffuse
      neoplastic lymphoid infiltration with necrosis. Light microscopy revealed starry
      sky patterns and immunohistochemical staining demonstrated atypical lymphocytes
      which stained for CD20, CD10, bcl-6, and Ki-67. After complete staging,
      chemotherapy was started and the patient is presently tumor free 41 months after
      the diagnosis. CONCLUSION: Burkitt's lymphoma arising from the uterus/cervix is
      extremely rare and may present as a pelvic mass. Early diagnosis, aggressive
      chemotherapy, +/-surgical intervention, plays an important role in management and
      survival of patients with Burkitt's lymphoma.

PMID- 19756678
TI  - The evaluation of vestibular functions in patients with pseudoexfoliation
      syndrome.
AB  - The main objective of the study is to evaluate vestibular system of the inner ear
      with postural tests in the patients with pseudoexfoliation syndrome (PEX). It is
      clinical case-control study. The study group included 34 patients with PEX and 40
      controls without PEX. The patients and controls underwent complete ophthalmic and
      otorhinolaryngologic examinations. Vestibular functions were done by Fitzgerald
      and Dix-Hallpike, caloric tests, Romberg test, tandem Gait test, Quiks test in
      both control and study groups. Pur-tone and high-frequency audiography were also
      performed in all cases. The mean patient age was 63 years (+/-11.80) (range 47-74
      years) in the PEX group and 65 years (+/-8.70) (range 61-68 years) in the control
      group with no differences among the two groups (P > 0.05). Although none of the
      34 patients with PEX had clinical history of balance disturbance, 21 (61.76%) had
      significant pathologic sign in vestibular function tests (P < or = 0.05), while
      only 3 (7.5%) of 40 cases in the control group had pathologic sign in vestibular
      function tests. The scales from pure tone and high-frequency audiogram in the PEX
      group were similar to those of the control group. In conclusion, the patients
      with PEX, there may be a vestibular involvement in the pathological level in the
      inner ear. Larger clinical studies, experimental animal studies, and post mortem
      studies in humans are needed to disclose the pathology in the vestibulocochlear
      system in the patients with PEX.

PMID- 19756679
TI  - The response to sodium valproate of patients with sinus headaches with normal
      endoscopic and CT findings.
AB  - The objectives of this study are to evaluate the patients who have sinus
      headaches, either self-ascribed or physician-diagnosed, and to determinate the
      response to sodium valproate in a prophylactic treatment of the patients without
      positive sino-nasal findings. "Sinus headache" is a patient's complaint or
      physician-diagnosis that can have a variety of underlying causes. The patients
      are often treated with multiple courses of antibiotics and occasionally undergo a
      sinus surgery, often with little or no relief of their symptoms. One hundred and
      four patients with "sinus headaches" were evaluated prospectively. The patients
      with a normal rigid nasal endoscopy and a paranasal sinus computed tomography
      scan were treated with sodium valproate as a prophylactic treatment. After a 3
      month follow-up, the patients' response to the treatment was evaluated. Seventy
      two patients (69.2%) did not have any positive sino-nasal findings in the nasal
      endoscopy and the computed tomography scanning. The response rate to the
      treatment for these patients was as follows: significant improvement in 44
      patients (61.1%), partial response (9.7%), no response (15.3%), and ten patients
      (13.9%) withdrew or failed to follow-up. According to Wilcoxon test, the
      patients' response rate to sodium valproate was statistically significant (P =
      0.001). In conclusion, a majority of "sinus headache" patients do not show any
      positive sino-nasal pathologic finding. Therefore, we have to consider migraine
      headache as a considerable cause and sodium valproate as an effective
      conservative treatment.

PMID- 19756680
TI  - Speech and swallowing after surgical treatment of advanced  oral and
      oropharyngeal carcinoma: a systematic review  of the literature.

PMID- 19756681
TI  - Outcome of conservation surgery for laryngeal carcinoma:  an 8-year trial.
AB  - The purpose of this report is to review the experience of our institution with
      conservative surgery for laryngeal cancer. In this retrospective study, a review
      was made of 85 patients treated with conservation surgery between 1998 and 2005.
      At least 2 years of follow-up period (mean 46.6 months) was achieved for all the
      patients. We evaluated age, tobacco and alcohol intake, T stage,
      histopathological differentiation and localization of tumor, subglottic
      extension, anterior commissure invasion, vocal cord mobility, surgical margins,
      type of surgery applied, and post-operative radiotherapy (pRT) applied. Local
      control and 2-year survival rates were estimated. We managed with horizontal,
      vertical, and horizontovertical laryngectomies in 55, 26, and 4 patients,
      respectively. 28 patients were scheduled to have pRT. The actuarial and overall
      local control rates were 82.4 and 94.1%, respectively. On univariable analysis,
      significant factors for increased recurrences were positive resection margins,
      low differentiation of tumor, alcohol consumption and incompletion of the planned
      pRT. The 2-year survival rate was 60 and 95.7% for patients with and without
      local recurrence, respectively. Conservation surgery is a safe procedure for
      laryngeal cancer in proper endications.

PMID- 19756682
TI  - Ear microbiology reports: a need for better communication with the
      microbiologists.
AB  - Most ENT surgeons treat discharging ears with topical antibiotics but many may
      not routinely utilise ear microbiology specimens. One reason could be that ear
      microbiology reports may not reflect their usual therapeutic options. This paper
      explores how microbiology departments in England process ear swabs. We carried
      out a telephone questionnaire of 104 microbiology departments in England. Results
      were obtained from 95 hospitals. Various culture methods are used, with
      sensitivity testing for up to 51 different antibiotics. Only five are licensed
      for topical use. Systemic antibiotics seemed to be preferentially tested for over
      topical antibiotics. Anaerobes and fungus are routinely tested. Many microbiology
      departments do not routinely report on all sensitivities tested. Antibiotic
      sensitivity testing for various micro-organisms cultured from ear swabs seemed to
      be guided by protocols for systemic infections. Microbiologists may not fully
      appreciate ENT surgeons' preferential usage of topical antibiotics in treating
      discharging ears, albeit there are other factors in their consideration for
      antibiotics to test. To gain better guidance from swab results, and to reduce
      needless lab costs, discussion with the microbiologists may be of benefit.

PMID- 19756683
TI  - Safety aspects of Cluster immunotherapy with semi-depot allergen  extracts in
      seasonal allergic rhinoconjunctivitis.
AB  - In addition to allergen avoidance and pharmaceutical medication, specific
      immunotherapy (SIT) stands for the third most important mainstay offered to
      allergic patients. SIT has been widely used in pollen-allergic rhinitis,and
      clinical efficacy has been validated in several controlled clinical trials.
      Classic SIT protocols begin with an initial dose-increase period (subcutaneous
      injections of gradually ascending dosages of the allergen extract in weekly
      intervals) followed by the dose-maintenance period.However, dosage schedules are
      not commonly standardized yet. Cluster-SIT is an accelerated procedure to achieve
      the maintenance dose after a shorter time interval by the application of 2-3
      injections per treatment day.A total of 395 pollen-allergic patients (173
      females,222 males) aging from 18 to 61 years (mean age 32.6 +/- 5.9 years) have
      been investigated using a Cluster schedule for Alutard SQ that allows up dosing
      up to 100,000 SQ-U in six treatment days (within 5 weeks). The schedule was
      investigated with regard to the side effects during dosage increase. The total
      number of systemic reactions was n = 148 or 2.05% of all injections. Of these,119
      (80%) were classified as immediate reactions, 27(18%) were late-phase reactions
      and 2 (2%) were both immediate- and late-phase reactions. Of all systemic
      reactions, 124 (84%) were classified as grade 1 reactions,and 24 (16%) as grade
      2. No reactions of grades 3 and 4 occurred. Age, gender and the type of the
      allergen used had no influence on the frequency or severity of local or systemic
      reactions. The appearance and amount of adverse side effects in Cluster-SCIT is
      comparable to those in conventional schedules. With respect to safety aspects,
      this accelerated dosage schedule could turn into an interesting alternative for
      dosage increase during subcutaneous immunotherapy (SCIT).

PMID- 19756684
TI  - Long-term outcome analysis after surgical salvage for recurrent  tonsil carcinoma
      following radical radiotherapy.
AB  - The objective of this study is to report the longterm outcomes of salvage surgery
      following local and/or regional failure of tonsillar carcinoma treated with
      standard fractionation radiotherapy. All cases of carcinoma of the tonsil treated
      by radical radiotherapy at the Princess Margaret Hospital between January 1970
      and December 1990 were reviewed retrospectively. Patients who underwent salvage
      surgery for local and/or regional recurrent squamous cell carcinoma of the tonsil
      following radiation therapy were included for analysis. 239 out of 640 patients
      with tonsillar carcinoma recurred post radiotherapy. 175 patients were deemed
      candidates for surgical salvage. At the time of the last follow-up, only 13
      patients were alive and 162 patients had died. The majority of patients (n = 96,
      59%)died with disease. The median time to death was approximately 1.3 years
      following salvage surgery. The 5-year overall survival rate was 23%. The 5-year
      cause-specific survival was 40%. The probability of death due to disease was
      higher than the probability of death due to other causes. Both N-classification
      and T-classification were found to be significant predictors of time to death. In
      conclusion,in spite of the fact that the patients in this study had been treated
      prior to the widespread introduction of altered fractionation and concurrent
      chemoradiation for advanced tonsil carcinoma, it demonstrates the poor prognosis
      of recurrent disease. Despite the poor prognosis, 20% of patients will be alive
      at 5 years and therefore salvage surgery should be considered when possible.

PMID- 19756685
TI  - Mental health after laryngectomy and partial laryngectomy:  a comparative study.
AB  - Patients treated for laryngeal cancer are confronted daily with the effects of
      the operation. The choice of treatment method can have a significant impact on
      psychosocial adjustment. Three hundred and six out-patients who underwent
      surgical treatment for laryngeal cancer within the last two decades were
      interviewed in their own homes using the structured clinical interview for DSM-IV
      (SCID).Psychiatric disorders were diagnosed among 17.3% of the partial
      laryngectomy patients (PL) and 22.2% of the patients with total laryngectomy
      (LE). In comparing four variables (age, time elapsed since diagnosis, gender and
      subjective speech intelligibility), subjective speech intelligibility and age
      were the variables with a unique, significant effect on the frequency of
      psychiatric disorders, albeit only in the case of PL patients. The need for
      psychosocial rehabilitation for patients with partial laryngectomy tends to be
      underestimated. It is concluded that screening for psychological variables and
      subjective speech intelligibility can be beneficial for the identification of out
      patients lacking appropriate treatment.

PMID- 19756686
TI  - 210Pb concentration in household dust: a potential indicator of long-term indoor
      radon exposure.
AB  - Radon decays to a long-lived isotope 210Pb with a half-life of about 22 years.
      Measuring concentrations of 210Pb in household dust could be an alternative
      method of determining indoor radon levels. This novel method for estimating long
      term radon concentration was explored in over a hundred Canadian residential
      homes. The results demonstrate that 210Pb concentrations in household dust relate
      reasonably well to radon concentrations in homes.

PMID- 19756687
TI  - Overestimation of Chernobyl consequences: calculation of a latent period for
      tumors with unproven radiation etiology.

PMID- 19756688
TI  - In vitro radioprotection studies of organoselenium compounds: differences between
      mono- and diselenides.
AB  - Organoselenium compounds belonging to the class of monoselenides, such as
      selenomethionine (SeM) and methylselenocysteine (MSeCys) and diselenides
      including selenocystine (SeCys) and selenopropionic acid (SePA), were examined
      for their comparative radioprotective effects using in vitro models. Effects of
      these compounds on the inhibition of gamma-radiation induced lipid peroxidation
      in liposomes, protein carbonylation in bovine serum albumin (BSA) and strand
      breaks in pBR322 plasmid DNA, assessed, respectively, by the formation of
      thiobarbituric acid reactive substances, formation of 2,2'-dinitrophenyl
      hydrazine (DNPH) carbonyl complex and horizontal gel electrophoresis, were used
      to compare their radioprotective ability. The IC 50 values for SeCys, SePA, SeM
      and MSeCys for lipid peroxidation were 27 +/- 1, 33 +/- 2, 200 +/- 8 and 163 +/-
      4 microM, respectively, and the values for inhibition of protein carbonylation
      were >200, 300 +/- 6, 464 +/- 8 and 436 +/- 3 microM, respectively. Inhibition of
      DNA strand break formation was tested at 200 microM for all the compounds and
      SePA and SeCys exhibited a protective effect on DNA, while SeM and MSeCys did not
      lead to any protection. The in vitro cytotoxicity studies in normal and tumor
      cells revealed that MSeCys and SeM were not cytotoxic to lymphocytes and EL4
      tumor cells at the concentrations employed. In contrast, SeCys was toxic, with a
      higher effect on tumor cells than lymphocytes. Our studies suggest that the non
      toxic diselenides like SePA should be explored as protective agents against gamma
      irradiation induced damage.

PMID- 19756689
TI  - SUMOylation is required for normal development of linear elements and wild-type
      meiotic recombination in Schizosaccharomyces pombe.
AB  - In the fission yeast, Schizosaccharomyces pombe, synaptonemal complexes (SCs) are
      not formed during meiotic prophase. However, structures resembling the axial
      elements of SCs, the so-called linear elements (LinEs) appear. By in situ
      immunostaining, we found Pmt3 (S. pombe's SUMO protein) transiently along LinEs,
      suggesting that SUMOylation of some component(s) of LinEs occurs during meiosis.
      Mutation of the SUMO ligase Pli1 caused aberrant LinE formation and reduced
      genetic recombination indicating a role for SUMOylation of LinEs for the
      regulation of meiotic recombination. Western blot analysis of TAP-tagged Rec10
      demonstrated that there is a Pli1-dependent posttranslational modification of
      this protein, which is a major LinE component and a distant homolog of the SC
      protein Red1. Mass spectrometry (MS) analysis revealed that Rec10 is both
      phosphorylated and ubiquitylated, but no evidence for SUMOylation of Rec10 was
      found. These findings indicate that the regulation of LinE and Rec10 function is
      modulated by Pli1-dependent SUMOylation of LinE protein(s) which directly or
      indirectly regulates Rec10 modification. On the side, MS analysis confirmed the
      interaction of Rec10 with the known LinE components Rec25, Rec27, and Hop1 and
      identified the meiotically upregulated protein Mug20 as a novel putative LinE
      associated protein.

PMID- 19756690
TI  - Divergence in centromere structure distinguishes related genomes in Coix lacryma
      jobi and its wild relative.
AB  - Knowledge about the composition and structure of centromeres is critical for
      understanding how centromeres perform their functional roles. Here, we report the
      sequences of one centromere-associated bacterial artificial chromosome clone from
      a Coix lacryma-jobi library. Two Ty3/gypsy-class retrotransposons, centromeric
      retrotransposon of C. lacryma-jobi (CRC) and peri-centromeric retrotransposon of
      C. lacryma-jobi, and a (peri)centromere-specific tandem repeat with a unit length
      of 153 bp were identified. The CRC is highly homologous to centromere-specific
      retrotransposons reported in grass species. An 80-bp DNA region in the 153-bp
      satellite repeat was found to be conserved to centromeric satellite repeats from
      maize, rice, and pearl millet. Fluorescence in situ hybridization showed that the
      three repetitive sequences were located in (peri-)centromeric regions of both C.
      lacryma-jobi and Coix aquatica. However, the 153-bp satellite repeat was only
      detected on 20 out of the 30 chromosomes in C. aquatica. Immunostaining with an
      antibody against rice CENH3 indicates that the 153-bp satellite repeat and CRC
      might be both the major components for functional centromeres, but not all the
      153-bp satellite repeats or CRC sequences are associated with CENH3. The
      evolution of centromeric repeats of C. lacryma-jobi during the polyploidization
      was discussed.

PMID- 19756691
TI  - Interferon alpha for the treatment of melanocytic conjunctival lesions.
AB  - BACKGROUND: To evaluate the effect of topical interferon alpha-2b therapy in the
      treatment of melanocytic conjunctival lesions. DESIGN: Non-comparative
      prospective case series. METHODS: Nine patients with histologically proven
      acquired melanosis with atypia and/or conjunctival melanoma were treated with
      recombinant IFN alpha-2b (Intron A, Essex Pharma, Luzern, Switzerland). The agent
      was diluted under sterile conditions to one million international units per ml
      Intron A and packed in single-dose units (EDO) by the pharmacy. It was stored in
      the refrigerator and applied 5 x 1 drop/day topically by the patient for 6 weeks.
      The patients were seen after 2 weeks and after the end of the treatment. Endpoint
      of the treatment was the complete regression of pigmentation or absence of
      cytological atypia in a re-biopsy. RESULTS: Seven lesions of nine patients showed
      regression and lost pigmentation. Three patients required a second cycle after
      the first therapy because of incomplete regression and one patient needed a third
      cycle of interferon. Only one of the patients needed a fourth cycle of therapy
      and additional surgery to show stable regression. The follow-up is 24.8 months
      (median). No local or systemic side-effects were encountered. The pre- and post
      treatment photos of two cases will be presented. CONCLUSIONS: Our observations
      suggest that topical interferon alpha-2b might be an effective agent for the
      adjuvant treatment of melanocytic conjunctival tumors without side-effects. It
      might be an alternative to other more toxic chemotherapeutical agents. A
      prospective multicenter study will help to finally evaluate the potential of
      topical interferon therapy for melanocytic conjunctival tumors, in particular PAM
      with atypia and minimal invasive conjunctival melanoma.

PMID- 19756692
TI  - Venous retinal flow reperfusion mechanisms following radial optic neurotomy with
      adjunctive intraocular triamcinolone in central retinal vein occlusion.
AB  - BACKGROUND: To evaluate retinal reperfusion, anastomosis, and compensation
      following radial optic neurotomy for ischemic nonperfused central retinal vein
      occlusion. METHODS: Prospective, non-comparative, interventional case series of
      13 patients with ischemic, nonperfused central retinal vein occlusion who
      underwent decompression surgery with a radial optic neurotomy and adjunctive
      intraocular triamcinolone. Patients were followed for 1 year after surgery, and
      were analyzed in the preoperative and postoperative stages determining: visual
      acuity by ETDRS chart (LogMar) and retinal thickness with optical coherence
      tomography. Fluorescein angiography was performed at regular intervals to
      evaluate the capillary perfusion grade. Intraocular pressure was measured and
      fundus was examined. RESULTS: Visual acuity and retinal thickness improved in
      10/13 (77%) patients after surgery at 1-year follow-up. Adequate retinal
      reperfusion was achieved in ten of the 13 eyes. Acute reperfusion occurred in six
      eyes within 2 weeks of surgery and a shunt vessel at the optic disk developed in
      four eyes within 4 months. In the remaining three eyes, retinal reperfusion was
      not observed by fluorescein angiography. No complications were noted in any of
      the patients. CONCLUSION: Surgical decompression promoted mechanical reperfusion
      of the occluded vessel in 10/13 (77%) cases. In 6/13 patients (46%) reperfusion
      occurred within 2 weeks of surgery, and in 4/13 patients (31%) collateral vessels
      formed within 4 months.

PMID- 19756693
TI  - Distribution of the epilepsy-related Lgi1 protein in rat cortical neurons.
AB  - The Lgi1 protein is involved in the pathogenesis of autosomal dominant lateral
      temporal epilepsy because mutations in the leucine-rich, glioma-inactivated 1
      (LGI1) gene have been found in affected subjects and families; however, the
      function of Lgi1 is still unclear. Definition of the fine intracellular
      distribution of Lgi1 in normal cortical tissue would add in understanding its
      role and envisage pathogenetic mechanisms. Therefore, we analyzed normal rat
      cortex for Lgi1 by combining biochemistry, immunohistochemistry and
      immunoelectron microscopy. Our results demonstrate that Lgi1 is a cytoplasmic
      protein distributed both in the soma and in the processes of neurons: it occurs
      on the rough endoplasmic reticulum, the site of synthesis, in the Golgi complex,
      where it undergoes glycosylation, and in close proximity to neurotubules and
      neurofilaments, especially in the axons, but it is scarce at synapses and the
      neurilemma. Lgi1 association with axonal cytoskeletal structures would imply Lgi1
      is either transported along axons by motor proteins, or playing some role as a
      carrier in the axonal Xux, or it could be involved in the regulation of
      cytoskeletal organization.

PMID- 19756694
TI  - High expression of antizyme inhibitor 2, an activator of ornithine decarboxylase
      in steroidogenic cells of human gonads.
AB  - High activity of ornithine decarboxylase (ODC), the rate-limiting enzyme of
      polyamine synthesis, is typically present in rapidly proliferating normal and
      malignant cells. The mitotically inactive steroidogenic cells in rodent testis
      and ovaries, however, also display high ODC activity. The activity of ODC in
      these cells responds to luteinizing hormone, and inhibition of ODC reduces the
      production of steroid hormones. Polyamines and ODC also control proliferation of
      germ cells and spermiogenesis. The activity of ODC, especially in proliferating
      cells, is regulated by antizyme inhibitor (AZIN). This protein displaces ODC from
      a complex with its inhibitor, antizyme. We have previously identified and cloned
      a second AZIN, i.e. antizyme inhibitor 2 (AZIN2), which has the highest levels of
      expression in brain and in testis. In the present study, we have used
      immunohistochemistry and in situ hybridization to localize the expression of
      AZIN2 in human gonads. We found a robust expression of AZIN2 in steroidogenic
      cells: testicular Leydig cells and Leydig cell tumors, in ovarian luteinized
      cells lining corpus luteum cysts, and in hilus cells. The results suggest that
      AZIN2 is not primarily involved in regulating the proliferation of the germinal
      epithelium, indicating a different role for AZIN1 and AZIN2 in the regulation of
      ODC. The localization of AZIN2 implies possible involvement in the gonadal
      synthesis and/or release of steroid hormones.

PMID- 19756695
TI  - Global gene expression profiling reveals a key role of CD44 in hepatic oval-cell
      reaction after 2-AAF/CCl4 injury in rodents.
AB  - Liver progenitors, so-called oval cells, proliferate remarkably from periportal
      areas after severe liver injury when hepatocyte regeneration is compromised.
      These cells invade far into the liver parenchyma. Molecular mechanisms underlying
      these behaviors of oval cells remain poorly understood. In this study, we treated
      rats with 2-acetylaminofluorene/carbon tetrachloride to induce hepatic oval
      cells. By expression microarray analysis, we investigated global gene expression
      profiles in liver tissue, with an emphasis on adhesion molecules, extracellular
      matrix proteins, matrix metalloproteinases (MMPs), growth factors/cytokines, and
      receptors that might contribute to the distinct behaviors of oval cells. Genes
      upregulated at least twofold were selected. We then performed immunostaining to
      verify the microarray results and identified expression of MMP-7 and CD44 in oval
      cells. Staining of cytokeratin (CK)-19, an oval-cell marker, was similar between
      oval cells located next to periportal areas and those located far within the
      parenchyma. In contrast, CD44 staining was more intense in the parenchyma than in
      periportal areas, suggesting a role of CD44 in oval-cell invasion. Moreover,
      newly differentiated CK-19+ hepatocytes within foci did not show CD44 staining,
      suggesting that CD44 is related to the undifferentiated oval-cell phenotype. We
      then investigated oval-cell reactivity in CD44-deficient mice fed an oval cell
      inducing diet of 3,5-diethoxycarbonyl-1,4-dihydrocollidine. Results showed
      significantly reduced oval-cell reactivity in CD44-deficient mice. Thus, oval
      cells express MMP-7 and CD44, and CD44 appears to play critical roles in the
      proliferation, invasion, and differentiation of hepatic oval cells in rodents.

PMID- 19756696
TI  - Comparing working conditions and physical and psychological  health complaints in
      four occupational groups working  in female-dominated workplaces.
AB  - BACKGROUND: Dominant theories of working conditions and their effects on poor
      employee health have been criticized for failing to consider how psychosocial
      factors interact and how such relationships may differ across occupational
      groups. GOAL: This paper examines the associations between psychosocial factors
      and physical and psychological health complaints while at the same time taking
      into account differences between occupational groups in female-dominated
      professions. METHOD: Four female-dominated occupational groups were included:
      nurses, health care assistants, cleaners, and dairy industry workers. The
      relationships between influence, emotional and quantitative demands, social
      support, back pain, and behavioural stress were examined using structural
      equation modelling. RESULTS: Results supported a group-specific model: the
      overall pattern remained the same across groups while psychosocial factors had
      different impacts on poor health and interacted differently across groups. The
      results also indicated links between psychosocial factors and poor physical
      health. CONCLUSION: The study confirmed the importance of differentiating between
      female-dominated occupations rather than talking about women's working conditions
      as such. The study also emphasized the importance of considering psychosocial
      risk factors when examining physical health, in this case back pain.

PMID- 19756697
TI  - A review of the data quality and comparability of case-control studies of low
      level exposure to benzene in the petroleum industry.
AB  - PURPOSE: Published case-control studies of risks of leukaemia following low
      exposures to benzene in the distribution of petroleum (gasoline) have not all
      identified the same level of risk, but the studies have had differences in cohort
      inclusion, case determination and availability of occupational and lifestyle
      data. We reviewed the quality and comparability of the data from three (of four)
      studies. METHODS: Through site visits, discussions with the investigators and
      reading study reports, we reviewed and audited the methods used for selecting
      cases and controls, for estimating individual exposures and for analysing and
      interpreting the data. Case-control comparisons of exposures were examined using
      customized graphs. RESULTS: We found that there were no issues of subject
      selection, methods or general data quality that were likely to have distorted
      their internal comparisons; we could not check in detail whether the metric for
      exposure assessments was the same across the studies; the exposure assessments
      for the Australian study required the least backward estimation, and the
      Canadian, which also had fewest cases, the most; evidence of an increased risk at
      higher exposures in Australia was convincing. CONCLUSIONS: The findings are
      consistent with some effect of benzene at higher lifetime exposures. A proposed
      pooled analysis should improve quantification of any exposure-response
      relationship.

PMID- 19756698
TI  - Clinical and HRCT screening of heavily asbestos-exposed workers.
AB  - PURPOSE: To characterize asbestosis today and to clarify the indications for high
      resolution computed tomography (HRCT) in the surveillance of heavily exposed
      workers. METHODS: Six hundred and twenty-seven workers were screened and HRCT
      findings were classified and divided in two groups: pulmonary fibrosis (n = 86)
      and no fibrosis (n = 541). RESULTS: Most (65/86 = 76%) of the detected fibrosis
      cases were mild. The magnitude of asbestos exposure showed an unexpected inverse
      relation with fibrosis. In multivariate analyses, age, forced expiratory volume
      in 1 s/forced vital capacity ratio, and poor diffusing capacity were associated
      with HRCT fibrosis, but asbestos exposure was not. CONCLUSIONS: Asbestosis seems
      to be characterized by mild fibrosis today even in heavily exposed workers. To
      avoid radiation exposure in HRCT, age and lung function data may be used only to
      a limited extent to select imaging candidates. Selection and recollection biases
      may distort the relation between asbestos exposure and fibrosis.

PMID- 19756699
TI  - The psychometric properties of demand-control and effort-reward imbalance scales
      among Brazilian nurses.
AB  - PURPOSE: To compare the psychometric adequacy of the demand-control-support (DCS)
      and the effort-reward imbalance (ERI) questionnaires in relation to their
      respective theoretical models among workers within the same psychosocial work
      environment. METHODS: A self-report questionnaire was administered to 1,509
      nursing personnel at two Brazilian hospitals. Analyses were based on internal
      consistency, corrected item-total correlation, and confirmatory factor analysis
      models for ordinal data (conducted with Mplus software) to test the fit of each
      model. RESULTS: Internal consistency was satisfactory (>0.70) for most scales of
      the DCS and ERI questionnaires, except for the job decision latitude scale (alpha
      = 0.50). With reference to corrected item-total correlations, adequate
      performance was observed for most items of both questionnaires. The item 'Do you
      have to do same thing over and over again' had a very low corrected item-total
      correlation (-0.09) and the removal of this item increased the internal
      consistency of the skill discretion subscale. Overall, fit indices (of factorial
      validity) for the DCS and the ERI questionnaires were adequate. However, a low
      correlation between subscales of the decision latitude scale (-0.164) was
      observed. For the psychological job demands and overcommitment scales, the best
      adjustment of the model was obtained when correlated errors between items were
      considered. CONCLUSIONS: Strengths and limitations were observed in both the DCS
      and the ERI scales. The questionnaires could be improved by the revision of some
      items.

PMID- 19756700
TI  - Time course of changes in immuneoendocrine markers following an international
      rugby game.
AB  - Intense exercise is known to cause temporary impairments in immune function. Few
      studies, however, have investigated the effects of intense competitive exercise
      on immunoendocrine variables in elite team sport athletes. The aim of this study
      was to evaluate the time course of changes in selected immunoendocrine and
      inflammatory markers following an international rugby union game. Blood samples
      were taken from players (n = 10) on camp entry, the morning of the game (pre),
      immediately after (post) and 14 and 38 h into a passive recovery period. Players
      lost 1.4 +/- 0.2 kg of body mass during the game (ambient conditions, 11 degrees
      C, 45% RH). An acute phase inflammatory response was observed as reflected
      through immediate increases in serum cortisol and IL-6 (post) followed by delayed
      increases in serum creatine kinase (CK; 14 h) activity and C-reactive protein
      (CRP; 38 h); P < 0.05. Decreases in the number of circulating T lympocytes, NK
      cells and bacteria-stimulated neutrophil degranulation were also observed post
      exercise (P < 0.05), indicative of decreased host immune protection. Following a
      large decrease in serum testosterone to cortisol (T/C) ratio immediately post and
      14 h after exercise, T/C values then increased above those observed at camp entry
      38 h into recovery (P < 0.05). This rebound anabolic stimulus may represent a
      physiological requirement for recovery following intense tissue damage resulting
      from game collisions. The findings also suggest that a game of international
      rugby elicits disturbances in host immunity, which last up 38 h into the recovery
      period.

PMID- 19756701
TI  - Running from Paris to Beijing: biomechanical and physiological consequences.
AB  - The purpose of this study was to examine the physiological and biomechanical
      changes occurring in a subject after running 8,500 km in 161 days (i.e. 52.8 km
      daily). Three weeks before, 3 weeks after (POST) and 5 months after (POST+5)
      running from Paris to Beijing, energy cost of running (Cr), knee flexor and
      extensor isokinetic strength and biomechanical parameters (using a treadmill
      dynamometer) at different velocities were assessed in an experienced ultra
      runner. At POST, there was a tendency toward a 'smoother' running pattern, as
      shown by (a) a higher stride frequency and duty factor, and a reduced aerial time
      without a change in contact time, (b) a lower maximal vertical force and loading
      rate at impact and (c) a decrease in both potential and kinetic energy changes at
      each step. This was associated with a detrimental effect on Cr (+6.2%) and a loss
      of strength at all angular velocities for both knee flexors and extensors. At
      POST+5, the subject returned to his original running patterns at low but not at
      high speeds and maximal strength remained reduced at low angular velocities (i.e.
      at high levels of force). It is suggested that the running pattern changes
      observed in the present study were a strategy adopted by the subject to reduce
      the deleterious effects of long distance running. However, the running pattern
      changes could partly be linked to the decrease in maximal strength.

PMID- 19756702
TI  - Difference in the metabolic cost of postural actions during iso- and
      antidirectional coupled oscillations of the upper limbs in the horizontal plane.
AB  - When oscillating the upper limbs in the horizontal plane, the effort required to
      maintain posture is higher when the limbs move isodirectionally (ISO coupling)
      than when they move mirror symmetrical, i.e., antidirectionally (ANTI). Movements
      stability and accuracy are much lower in ISO than in ANTI and the higher postural
      requests may be one factor contributing to the coordination deficiency of ISO
      movements. On this background, we measured the metabolic cost of ISO and ANTI
      movements in order to (1) quantitatively evaluate the supplemental effort
      required by ISO coupling, (2) establish whether it can be entirely ascribed to
      postural activities, and (3) compare it with the effort paid for the primary
      movement. Breath-by-breath metabolic (VO2, VCO2) and cardio-respiratory (HR, VE)
      parameters were measured in six participants, who performed intermittent
      exercises (5 min long, 12 s movement, 12 s rest) of cyclic arm adduction
      abduction in the horizontal plane with either one arm or both arms in ISO or ANTI
      coupling, at 1.4 and 2.0 Hz. A force platform recorded the reaction forces to
      ground and the torque about the trunk vertical axis (Tz). At both frequencies and
      at metabolic steady-state, the mean values of both VO2 and Tz were found to be
      larger during ISO than ANTI coupling. Moreover, a linear relation was found
      between metabolic cost and Tz. Lastly, during ANTI coupling virtually all the
      energy was spent for the primary movement whilst the large increase in energy
      expenditure when passing from ANTI to ISO was almost entirely ascribable to
      postural activities.

PMID- 19756703
TI  - Relationship of an advanced glycation end product, plasma carboxymethyl-lysine,
      with slow walking speed in older adults: the InCHIANTI study.
AB  - Advanced glycation end products (AGEs) are bioactive molecules found in foods and
      generated endogenously in the body. AGEs induce cross-linking of collagen and
      increase the stiffness of skeletal muscle and cartilage. We characterized the
      relationship between a plasma AGE, carboxymethyl-lysine (CML), and slow walking
      speed (lowest quintile of walking speed) in older adults. Walking speed over a 4
      m course was assessed in 944 adults, aged >or=65 years, in the InCHIANTI study, a
      population-based study of aging and mobility disability conducted in two towns in
      Tuscany, Italy. Participants in the highest quartile of plasma CML were at higher
      risk of slow walking speed (Odds Ratio [O.R.] 1.56, 95% Confidence Interval
      [C.I.] 1.02-2.38, P = 0.04) compared to those in the lower three quartiles of
      plasma CML in a logistic regression models adjusting for age, education,
      cognitive function, smoking, and chronic diseases. After exclusion of
      participants with diabetes, participants in the highest quartile of plasma CML
      were at higher risk of slow walking speed (O.R. 1.87, 95% C.I. 1.15-3.04, P =
      0.01) adjusting for the same covariates. In older community-dwelling adults,
      elevated plasma CML is independently associated with slow walking speed.

PMID- 19756704
TI  - Vitamin D receptor gene FokI polymorphisms influence bone mass in adolescent
      football (soccer) players.
AB  - The genetic influence on bone mineralization during adolescence is unclear
      possibly due to modifying factors such as skeletal maturation and lifestyle. We
      evaluated the influence of polymorphisms of the vitamin D receptor (VDR) gene on
      longitudinal changes in bone mass, bone- and calcium-related hormones in 46
      adolescent soccer players (11.8-14.2 years). Total body bone mineral content
      (TBMC) and density (TBMD) were measured at baseline and after 6 months. Insulin
      like growth factor-I (IGF-1), testosterone, intact parathyroid hormone, and
      activity of plasma bone alkaline phosphatase were measured at baseline and after
      3 months. The influence of FokI or TaqI VDR genotypes on changes in the outcome
      variables were analyzed by univariate ANOVA with adjustment for chronological
      age, skeletal age and body weight at baseline. At baseline, boys with Ff genotype
      had higher TBMC, TBMD, TBMD Z-score compared to those with FF genotype (P <
      0.05). After 3 months, Ff boys also had higher increment in plasma IGF-1 (P <
      0.05). FokI polymorphism did not influence changes in bone mass measurements
      after 6 months, although differences detected at baseline remained significant
      after 6 months. There were no differences in the outcome variables according to
      TaqI genotypes. This study demonstrates that FokI polymorphisms affect bone mass
      in Brazilian adolescent soccer players and suggests that the FokI effect on bone
      mineralization occurs during bone maturation, possibly at the initial pubertal
      stages.

PMID- 19756705
TI  - Neural adaptations underlying cross-education after unilateral strength training.
AB  - The purpose of this study was to investigate the effects of 4-week (16 sessions)
      unilateral, maximal isometric strength training on contralateral neural
      adaptations. Subjects were randomised to a strength training group (TG, n = 15)
      or to a control group (CG, n = 11). Both legs of both groups were tested for
      plantar flexion maximum voluntary isometric contractions (MVCs), surface
      electromyogram (EMG), H-reflexes and V-waves in the soleus (SOL) and
      gastrocnemius medialis (GM) superimposed during MVC and normalised by the M-wave
      (EMG/M(SUP), H(SUP)/M(SUP), V/M(SUP), respectively), before and after the
      training period. For the untrained leg, the TG increased compared to the CG for
      MVC torque (33%, P < 0.01), SOL EMG/M(SUP) (32%, P < 0.05) and SOL V/M(SUP) (24%,
      P < 0.05). For the trained leg, the TG increased compared to the CG for MVC
      torque (40%, P < 0.01), EMG/M(SUP) (SOL: 38%, P < 0.05; GM: 60%, P < 0.05) and
      SOL V/M(SUP) (72%, P < 0.01). H(SUP)/M(SUP) remained unchanged for both limbs. No
      changes occurred in the CG. These results reinforce the concept that enhanced
      neural drive to the contralateral agonist muscles contributes to cross-education
      of strength.

PMID- 19756706
TI  - Hypoxic training increases metabolic enzyme activity and composition of alpha
      myosin heavy chain isoform in rat ventricular myocardium.
AB  - Cardiac muscle adaptation is essential for maintaining physical capacity after
      ascending to high altitude. This study examines the effects of high altitude
      training on myocardial metabolic enzyme activity and composition of alpha-myosin
      heavy chain (MHC). Rats were randomly divided into normobaric sedentary (NS) and
      training (NT) groups, and hypobaric sedentary (HS) and training (HT) groups. HS
      and HT rats were exposed to hypobaric hypoxia (simulated 4,000-5,000 m) for 5
      weeks (24 h/day), and HT rats simultaneously received swim training. Hypoxia
      exposure for 5 weeks led to a decrease in succinate dehydrogenase (SDH) and
      citrate synthase (CS) activities in the left ventricle (LV), and a decrease in
      CS, hexokinase (HK) and total lactate dehydrogenase (LDH) activities in the right
      ventricle (RV) (p < 0.05, HS vs. NS). Furthermore, 1 h/day swim training during
      hypoxia exposure enhanced the CS activity in LV and the SDH and CS activities in
      RV (p < 0.05, HT vs. HS). The percentages of alpha-MHC in both ventricles in HT
      were higher than those in HS (p < 0.05). We conclude that exercise training at
      high altitude is beneficial for cardiac muscle adaptation to hypoxia by
      increasing activities of enzymes and percentage of alpha-MHC. This may contribute
      to improved cardiac function and work capacity at high altitude.

PMID- 19756707
TI  - Intermittent hypoxic training: doping or what?

PMID- 19756708
TI  - Whole body immersion and hydromineral homeostasis: effect of water temperature.
AB  - This experiment was designed to assess the effects of prolonged whole body
      immersion (WBI) in thermoneutral and cold conditions on plasma volume and
      hydromineral homeostasis.10 navy "combat swimmers" performed three static 6-h
      immersions at 34 degrees C (T34), 18 degrees C (T18) and 10 degrees C (T10).
      Rectal temperature, plasma volume (PV) changes, plasma proteins, plasma and urine
      ions, plasma osmolality, renin, aldosterone and antidiuretic hormone (ADH) were
      measured. Results show that compared to pre-immersion levels, PV decreased
      throughout WBI sessions, the changes being markedly accentuated in cold
      conditions. At the end of WBI, maximal PV variations were -6.9% at T34, -14.3% at
      T18, and -16.3% at T10. Plasma osmolality did not change during and after T34
      immersion, while hyperosmolality was present at the end of T18 immersion and
      began after only 1 h of T10 immersion. In the three temperature conditions,
      significant losses of water (1.6-1.7 l) and salt (6-8 g) occurred and were
      associated with similar increases in osmolar and free water clearances.
      Furthermore, T18 and T10 immersions increased the glomerular filtration rate.
      There was little or no change in plasma renin and ADH, while the plasma level of
      aldosterone decreased equally in the three temperature conditions. In conclusion,
      our data indicate that cold water hastened PV changes induced by immersion, and
      increased the glomerular filtration rate, causing larger accumulated water
      losses. The iso-osmotic hypovolemia may impede the resumption of baseline fluid
      balance. Results are very similar to those repeatedly described by various
      authors during head-out water immersion.

PMID- 19756709
TI  - Physiological factors to predict on traditional rowing performance.
AB  - The purpose of this study was to determine the best prediction factors of
      traditional rowing performance in traditional elite (ER) and amateur (AR) rowers.
      Average power during the 20-min all-out test (W(20 min)), average power output
      which elicited a blood lactate concentration of 4 mmol l(-1) (W(4 mmol l(-1))),
      power output in 10 maximal strokes (W(10 strokes)), maximal strength and muscle
      power output during a bench pull (BP) and anthropometric values were all measured
      for 46 trained male rowers aged 21-30 with 8-15 years of rowing training
      experience. The ER group showed greater body mass (5%, p < 0.05), greater fat
      free body mass (5%, p < 0.05), greater 1RM(BP) (13%, p < 0.001), longer training
      experience (43%, p < 0.001), and a shorter time in the 2,000 m test (4%, p <
      0.05) than the AR group. The ER group showed higher power output values in W(10
      strokes) (9%, p < 0.01), W(20 min) (15.4%, p < 0.01) and (W(4 mmol l(-1)))
      (17.8%, p < 0.01) compared with the AR group. Significant relationships were
      observed between (W(4 mmol l(-1))) and W(20 min) (r = 0.65 and 0.80; p < 0.01 in
      ER and AR, respectively). The indices for rowing performance suggested that W(20
      min), (W(4 mmol l(-1))), W(10 strokes) and 1RM(BP) were the most important
      predictors of traditional rowing performance in elite and amateur rowers.

PMID- 19756710
TI  - Force variability during isometric wrist flexion in highly skilled and sedentary
      individuals.
AB  - The association of expertness in specific motor activities with a higher ability
      to sustain a constant application of force, regardless of muscle length, has been
      hypothesized. Ten highly skilled (HS group) young tennis and handball athletes
      and 10 sedentary (S group) individuals performed maximal and submaximal (5, 10,
      20, 50, and 75% of the MVC) isometric wrist flexions on an isokinetic dynamometer
      (Kin-Com, Chattanooga). The wrist joint was fixed at five different angles (230,
      210, 180, 150, and 1300). For each position the percentages of the maximal
      isometric force were calculated and participants were asked to maintain the
      respective force level for 5 s. Electromyographic (EMG) activation of the Flexor
      Carpi Ulnaris and Extensor Digitorum muscles was recorded using bipolar surface
      electrodes. No significant differences were observed in maximal isometric
      strength between HS and S groups. Participants of HS group showed significantly
      (P < 0.05) smaller force coefficient of variability (CV) and SD values at all
      submaximal levels of MVC at all wrist angles. The CV and SD values remained
      unaltered regardless of wrist angle. No difference in normalized agonist and
      antagonist EMG activity was observed between the two groups. It is concluded that
      long-term practice could be associated with decreased isometric force variability
      independently from muscular length and coactivation of the antagonist muscles.

PMID- 19756711
TI  - Coordination between upper- and lower-limb movements is different during
      overground and treadmill walking.
AB  - Locomotion studies employ either treadmill (TW) or overground walking (OW),
      considering that differences between them are negligible. The present study tests
      this notion by comparing coordination between upper- and lower-limb movements in
      healthy individuals during OW and TW at matched speeds. Results indicated that TW
      induced a higher cadence, which highly influenced interlimb coordination, in
      terms of frequency coupling and relative phase between arm and thigh motion. At
      low speed, the 2:1 pattern (double arm swing per stride) displayed lower
      incidence in TW compared to OW, and this was correlated with a lower sagittal
      acceleration at the shoulders, at twice the stride frequency, in the former
      condition. The low occurrence of the 2:1 coupling in TW, moreover, was correlated
      to a preferential adoption of a cadence exceeding 80% of the arm's resonant
      frequency, whereas higher incidence of this pattern in OW involved a preferential
      cadence below the 80% threshold. Results indicated also that the relative phase
      between arm and ipsilateral thigh swinging was smaller in TW, in relation to an
      earlier occurrence of maximum thigh extension, shortened stance phase, and
      increased cadence. These findings suggest that arm-leg coordination is different
      in OW and TW, and that difference can be mainly ascribed to condition-specific
      setting of central mechanisms for scaling stride frequency, for controlling
      dynamic axial posture (sagittal shoulder acceleration), and, possibly, for
      maintaining inter-limb synchrony. Awareness of a different "motor set" in TW and
      OW is critical if data from the two paradigms are used in physiological and patho
      physiological studies.

PMID- 19756712
TI  - Neuromuscular adaptations to 8-week strength training: isotonic versus isokinetic
      mode.
AB  - Previous studies attempted to compare the effectiveness of isokinetic and
      isotonic training. However, they have provided conflicting results. The purpose
      of this study was to compare the effects of isotonic versus isokinetic
      standardized concentric strength training programs of the knee extensors on the
      neuromuscular system. The standardization of these two training programs was
      ensured by the equalization of the total external amount of work performed and
      the mean angular movement velocity. Thirty healthy male students were randomly
      assigned to the isotonic (IT; n = 11), the isokinetic (IK; n = 11) or the control
      (C; n = 8) group. Both IT and IK groups trained their dominant lower leg 3
      sessions/week for 8 weeks on a dynamometer. The IT group exercised using a preset
      torque of 40% of the maximal voluntary isometric torque at 70 degrees (0 degrees
      = leg in horizontal position). The IK group exercised at a velocity ranging
      between 150 degrees and 180 degrees s(-1). Isotonic, isokinetic and isometric
      tests were performed on a dynamometer before and after strength training. Surface
      electromyographic activity of vastus lateralis, vastus medialis, rectus femoris,
      semitendinosus and biceps femoris muscles was recorded during the tests.
      Significant strength increases in both dynamic and static conditions were noticed
      for IT and IK groups without any significant difference between the two trained
      groups. Agonist muscle activity also increased with training but no change in
      antagonist muscle co-activity was observed. The two training methods could be
      proposed by clinicians and athletic coaches to improve concentric muscle strength
      in dynamic and static conditions.

PMID- 19756713
TI  - Impact of Loughborough Intermittent Shuttle Test versus soccer match on
      physiological, biochemical and neuromuscular parameters.
AB  - The aim of the present study was to analyze the impact of Loughborough
      Intermittent Shuttle Test (LIST) versus soccer match on heart rate (HR), muscle
      damage, redox status, blood leukocytes and neuromuscular function throughout 72 h
      recovery. Sixteen male soccer players (21.3 +/- 1.1 years; 175.0 +/- 6.0 cm; 70.7
      +/- 6.3 kg) completed LIST and performed a soccer match separated by 2 weeks and
      data were collected before, 30 min, 24, 48 and 72 h after LIST and match. HR,
      plasma creatine kinase (CK) activity, myoglobin (Mb), uric acid (UA), protein
      sulfhydryls (-SH), malondialdehyde (MDA) contents, total antioxidant status
      (TAS), blood leukocyte counts, delayed onset muscle soreness, 20 m sprint and
      jump performances, and maximal isokinetic knee extension and flexion were
      analyzed. HR after LIST was significantly lower than after the match. Post-match
      TAS was lower and UA was higher than after LIST. Thirty minutes and 24 h after
      soccer MDA was higher and -SH was lower than after LIST (P < 0.05). LIST and
      soccer match induced elevation in total leukocytes and a reduction in lymphocytes
      at 30 min. This reduction in blood lymphocytes 30 min after match was lower than
      after LIST. In conclusion, the impact of both exercises did not differ regarding
      the observed muscle damage markers and some neuromuscular parameters, although
      soccer requires higher cardiac demand and induced higher changes on redox status,
      adenine nucleotide metabolism and on lymphocyte counts than LIST, which should be
      taken into account when using LIST to simulate a match to study these type of
      physiological and biochemical-related endpoints.

PMID- 19756714
TI  - Evidence against a direct role of klotho in insulin resistance.
AB  - The klotho gene may be involved in the aging process. Klotho is a coactivator of
      FGF23, a regulator of phosphate and vitamin D metabolism. It has also been
      reported to be downregulated in insulin resistance syndromes and paradoxically to
      directly inhibit IGF-1 and insulin signaling. Our aim was to study klotho's
      regulation and effects on insulin and IGF-1 signaling to unravel this paradox. We
      studied klotho tissue distribution and expression by quantitative real-time
      polymerase chain reaction and Western blotting in obese Zucker rats and high-fat
      fed Wistar rats, two models of insulin resistance. Klotho was expressed in
      kidneys but at much lower levels (<1.5%) in liver, muscle, brain, and adipose
      tissue. There were no significant differences between insulin resistant and
      control animals. We next produced human recombinant soluble klotho protein (KLEC)
      and studied its effects on insulin and IGF-1 signaling in cultured cells. In
      HEK293 cells, FGF23 signaling (judged by FRS2-alpha and ERK1/2 phosphorylation)
      was activated by conditioned media from KLEC-producing cells (CM-KLEC); however,
      IGF-1 signaling was unaffected. CM-KLEC did not inhibit IGF-1 and insulin
      signaling in L6 and Hep G2 cells, as judged by Akt and ERK1/2 phosphorylation. We
      conclude that decreased klotho expression is not a general feature of rodent
      models of insulin resistance. Further, the soluble klotho protein does not
      inhibit IGF-1 and/or insulin signaling in HEK293, L6, and HepG2 cells, arguing
      against a direct role of klotho in insulin signaling. However, the hypothesis
      that klotho indirectly regulates insulin sensitivity via FGF23 activation remains
      to be investigated.

PMID- 19756716
TI  - High glucose inhibits HCO3(-) and fluid secretion in rat pancreatic ducts.
AB  - Cellular mechanisms underlying the impairment of pancreatic fluid and electrolyte
      secretion in diabetes were examined using interlobular ducts isolated from rat
      pancreas. Fluid secretion was assessed by monitoring changes in luminal volume.
      HCO3(-) uptake across the basolateral membrane was estimated from the recovery of
      intracellular pH following an acid load. Exposure to high glucose concentrations
      inhibited fluid secretion and reduced the rate of basolateral HCO3(-) uptake in
      secretin-stimulated ducts isolated from normal rats. In ducts isolated from
      streptozotocin-treated diabetic rats, fluid secretion and basolateral HCO3(-)
      uptake were also severely impaired but could be largely reversed by incubation in
      normal-glucose solutions. Sodium-dependent glucose cotransporter 1 (SGLT1),
      glucose transporter (GLUT)1, GLUT2, and GLUT8 transcripts were detected by
      reverse transcriptase polymerase chain reaction in isolated ducts. Raising the
      luminal glucose concentration in microperfused ducts caused a depolarization of
      the membrane potential, consistent with the presence of SGLT1 at the apical
      membrane. Unstimulated ducts filled with high-glucose solutions lost luminal
      fluid by a phlorizin-sensitive mechanism, indicating that pancreatic ducts are
      capable of active glucose reabsorption from the lumen via SGLT1. In ducts exposed
      to high glucose concentrations, continuous glucose diffusion to the lumen and
      active reabsorption via SGLT1 would lead to elevation of intracellular Na+
      concentration and sustained depolarization of the apical membrane. These two
      factors would tend to inhibit the basolateral uptake and apical efflux of Cl(-)
      and HCO3(-) and could therefore account for the impaired fluid and electrolyte
      secretion that is observed in diabetes.

PMID- 19756717
TI  - Telomere biology in healthy aging and disease.
AB  - Aging is a biological process that affects most cells, organisms and species.
      Telomeres have been postulated as a universal biological clock that shortens in
      parallel with aging in cells. Telomeres are located at the end of the chromosomes
      and consist of an evolutionary conserved repetitive nucleotide sequence ranging
      in length from a few hundred base pairs in yeast till several kilo base pairs in
      vertebrates. Telomeres associate with shelterin proteins and form a complex
      protecting the chromosomal deoxyribonucleic acid (DNA) from recognition by the
      DNA damage-repair system. Due to the "end-replication problem" telomeres shorten
      with each mitotic cycle resulting in cumulative telomere attrition during aging.
      When telomeres reach a critical length the cell will not further undergo cell
      divisions and become senescent or otherwise dysfunctional. Telomere shortening
      has not only been linked to aging but also to several age associated diseases,
      including tumorigenesis, coronary artery disease, and heart failure. In the
      current review, we will discuss the role of telomere biology in relation to aging
      and aging associated diseases.

PMID- 19756718
TI  - Cardiovascular determinants of life span.
AB  - The prevalence of cardiovascular diseases rises with aging and is one of the main
      causes of mortality in western countries. In view of the progressively aging
      population, there is an urge for a better understanding of age-associated
      cardiovascular diseases and its underlying molecular mechanisms. The risk factors
      for cardiovascular diseases include unhealthy diet, diabetes, obesity, smoking,
      alcohol consumption, physical inactivity, and aging. Increased production of
      oxygen-derived free radicals plays an important role in mediating cardiovascular
      diseases. Oxidative stress affects the availability and/or balance of key
      regulators of vascular homeostasis and favors the development of cardiovascular
      diseases. Reactive oxygen species are generated by different intracellular
      molecular pathways principally located in the cytoplasm and in the mitochondria.
      The mitochondrial protein p66Shc and the deacetylase enzyme SIRT1 were shown to
      be involved in different aspects of cardiovascular diseases. This review focuses
      on the latest scientific advances in understanding cardiovascular diseases
      associated to aging, as well as delineating the possible therapeutic implications
      of p66Shc and SIRT 1 in this process.

PMID- 19756719
TI  - Mitochondrial function as a determinant of life span.
AB  - Average human life expectancy has progressively increased over many decades
      largely due to improvements in nutrition, vaccination, antimicrobial agents, and
      effective treatment/prevention of cardiovascular disease, cancer, etc. Maximal
      life span, in contrast, has changed very little. Caloric restriction (CR)
      increases maximal life span in many species, in concert with improvements in
      mitochondrial function. These effects have yet to be demonstrated in humans, and
      the duration and level of CR required to extend life span in animals is not
      realistic in humans. Physical activity (voluntary exercise) continues to hold
      much promise for increasing healthy life expectancy in humans, but remains to
      show any impact to increase maximal life span. However, longevity in
      Caenorhabditis elegans is related to activity levels, possibly through
      maintenance of mitochondrial function throughout the life span. In humans, we
      reported a progressive decline in muscle mitochondrial DNA abundance and protein
      synthesis with age. Other investigators also noted age-related declines in muscle
      mitochondrial function, which are related to peak oxygen uptake. Long-term
      aerobic exercise largely prevented age-related declines in mitochondrial DNA
      abundance and function in humans and may increase spontaneous activity levels in
      mice. Notwithstanding, the impact of aerobic exercise and activity levels on
      maximal life span is uncertain. It is proposed that age-related declines in
      mitochondrial content and function not only affect physical function, but also
      play a major role in regulation of life span. Regular aerobic exercise and
      prevention of adiposity by healthy diet may increase healthy life expectancy and
      prolong life span through beneficial effects at the level of the mitochondrion.

PMID- 19756720
TI  - Insulin signaling and life span.
AB  - Hyperinsulinemia and metabolic diseases are known to be associated with a
      reduction in life span. In the presence of insulin resistance, insulin signaling
      is selectively impaired, contributing to longevity shortening. Insulin indeed
      activates a complex web of intracellular downstream pathways, which are involved
      in mechanisms regulating longevity, primarily affecting cellular proliferation
      and apoptosis. Insulin resistance promotes reactive oxygen species (ROS)
      formation and favors a pro-inflammatory milieu, both these conditions playing a
      critical role in the reduction of life span. Insulin resistance/hyperinsulinemia
      also influences longevity regulating other intracellular signaling downstream in
      a direct or indirect manner, such as the phosphoinositide 3-kinase pathway that
      appears selectively impaired by insulin resistance. Decreased NAD-dependent
      deacetylase sirtuin (Sirt) 1 activity may mediate the shortened life span in
      conditions of insulin resistance. Furthermore, insulin resistance and diabetes
      may also associate with the telomere shortening, another important regulator of
      life span. This review will focus on the main intracellular pathways and
      mediators regulated by insulin and altered by hyperinsulinemia/insulin
      resistance; it summarizes the underlying mechanisms and provides evidence of
      these observations in experimental animal models and in human, giving further
      insight on the hypothesis that insulin signaling may play an important role in
      life span.

PMID- 19756721
TI  - Specificities of olfactory receptor neuron responses to amino acids in the black
      bullhead catfish (Ameiurus melas).
AB  - In vivo investigations of catfish olfactory receptor neurons (ORNs) were
      previously limited to studying responses of spontaneously active cells. The
      olfactory organ, however, also contains ORNs that lack spontaneous activity and
      respond to amino acids. To record electrical activity of ORNs that were inactive
      prior to stimulation, we bathed the olfactory organ with low conductive, highly
      purified water that reduces shunting and enables detection of action potentials
      from ORNs distant to the electrode. After stimulation with amino acids, these
      ORNs elicited either phasic-tonic or tonic only activities. The spike frequency
      of the phasic activity consisted of transient frequencies up to 108 Hz that
      lasted <450 ms. All tonic activities saturated at action potential frequencies of
      17-21 Hz. Their durations were dose dependent over several log units of
      concentration as they closely followed that of the suprathreshold amino acid
      stimulation. Specificities of 44 ORNs were investigated with ten different amino
      acids tested at 10(-4) M. Thirteen ORNs were excited by only one amino acid, L
      norvaline, and 22 additional ORNs were excited by L-norvaline and L-methionine.
      Nine ORNs were excited by >2 amino acids that included L: -norvaline. In 29 of 31
      neurons responding to >1 amino acid, the duration of the responses to the most
      stimulatory amino acid was at least double compared to that to the other amino
      acids. The amplitude of electro-olfactogram (EOG) correlated significantly with
      the number of ORNs activated by the same amino acids confirming that the EOG
      represents the sum of ORN receptor potentials.

PMID- 19756722
TI  - Probing the bradycardic drug binding receptor of HCN-encoded pacemaker channels.
AB  - If (or Ih), encoded by the hyperpolarization-activated, cyclic nucleotide-gated
      (HCN1-4) channel gene family, contributes significantly to cardiac pacing.
      Bradycardic agents such as ZD7288 that target HCN channels have been developed,
      but the molecular configuration of their receptor is poorly defined. Here, we
      probed the drug receptor by systematically introducing alanine scanning
      substitutions into the selectivity filter (C347A, I348A, G349A, Y350A, G351A in
      the P-loop), outer (P355A, V356A, S357A, M358A in the P-S6 linker), and inner
      (M377A, F378A, V379A in S6) pore vestibules of HCN1 channels. When heterologously
      expressed in human embryonic kidney 293 cells for patch-clamp recordings, I348A,
      G349A, Y350A, G351A, P355A, and V356A did not produce measurable currents. The
      half-blocking concentration (IC50) of wild type (WT) for ZD7288 was 25.8+/
      9.7microM. While the IC50 of M358A was identical to WT, those of C347A, S357A,
      F378A, and V379A markedly increased to 137.6+/-56.4, 113.3+/-34.1, 587.1+/-167.5,
      and 1726.3+/-673.4microM, respectively (p<0.05). Despite the proximity of the S6
      residues studied, M377A was hypersensitive (IC50=5.1+/-0.7microM; p<0.05)
      implicating site specificity. To explore the energetic interactions among the S6
      residues, double and triple substitutions (M377A/F378A, M377A/V379A, F378A/V379A,
      and M377A/F378A/V379A) were generated for thermodynamic cycle analysis. Specific
      interactions with coupling energies (deltadeltaG)>1kT for M377-F378 and F378-V379
      but not M377-V379 were identified. Based on these new data and others, we
      proposed a refined drug-blocking model that may lead to improved antiarrhythmics
      and bioartificial pacemaker designs.

PMID- 19756723
TI  - Harmonin-b, an actin-binding scaffold protein, is involved in the adaptation of
      mechanoelectrical transduction by sensory hair cells.
AB  - We assessed the involvement of harmonin-b, a submembranous protein containing PDZ
      domains, in the mechanoelectrical transduction machinery of inner ear hair cells.
      Harmonin-b is located in the region of the upper insertion point of the tip link
      that joins adjacent stereocilia from different rows and that is believed to gate
      transducer channel(s) located in the region of the tip link's lower insertion
      point. In Ush1c (dfcr-2J/dfcr-2J) mutant mice defective for harmonin-b, step
      deflections of the hair bundle evoked transduction currents with altered speed
      and extent of adaptation. In utricular hair cells, hair bundle morphology and
      maximal transduction currents were similar to those observed in wild-type mice,
      but adaptation was faster and more complete. Cochlear outer hair cells displayed
      reduced maximal transduction currents, which may be the consequence of moderate
      structural anomalies of their hair bundles. Their adaptation was slower and
      displayed a variable extent. The latter was positively correlated with the
      magnitude of the maximal transduction current, but the cells that showed the
      largest currents could be either hyperadaptive or hypoadaptive. To interpret our
      observations, we used a theoretical description of mechanoelectrical transduction
      based on the gating spring theory and a motor model of adaptation. Simulations
      could account for the characteristics of transduction currents in wild-type and
      mutant hair cells, both vestibular and cochlear. They led us to conclude that
      harmonin-b operates as an intracellular link that limits adaptation and engages
      adaptation motors, a dual role consistent with the scaffolding property of the
      protein and its binding to both actin filaments and the tip link component
      cadherin-23.

PMID- 19756724
TI  - Transcriptional regulation of anthocyanin biosynthesis in red cabbage.
AB  - The color of red cabbage (Brassica oleracea var. capitata) is due to anthocyanin
      accumulation. To investigate the regulatory control of anthocyanin production in
      red cabbage, the expression of anthocyanin biosynthetic and regulatory genes from
      eight commercial cultivars was examined. While the four green varieties had
      negligible amount of anthocyanins under normal growth condition, the four red
      cultivars contained up to 1.60 mg g(-1) fresh weight. HPLC analysis of the four
      red cultivars revealed that they produced similar composition of various forms of
      cyanidin glucosides but at different concentrations. Molecular analysis indicated
      that all the red cabbage shared common mechanism of regulatory control for
      anthocyanin biosynthesis. Except CHI which showed similar expression levels
      between green and red cultivars, the other structural genes, CHS, F3H, F3'H, DFR,
      LDOX, and GST, were constitutively up-regulated during all stages of vegetative
      growth in red varieties. The expression of these structural genes was also
      dramatically increased in green and red cabbage under nutrient stresses. The
      increased expression of the structural genes coincided with a coordinated
      increase in transcript levels of a bHLH gene, BoTT8, and a MYB transcription
      factor, BoMYB2. These results indicate that activation of these two regulatory
      factors by unknown mechanisms constitutively up-regulates nearly the entire
      pathway genes for the onset of anthocyanin biosynthesis in red cabbage. Moreover,
      the amount of total anthocyanins in red cabbage was found to be positively
      correlated with total antioxidant power, implicating the potential health benefit
      of red cabbage to human health.

PMID- 19756725
TI  - Cell proliferation, cell shape, and microtubule and cellulose microfibril
      organization of tobacco BY-2 cells are not altered by exposure to near
      weightlessness in space.
AB  - The microtubule cytoskeleton and the cell wall both play key roles in plant cell
      growth and division, determining the plant's final stature. At near
      weightlessness, tubulin polymerizes into microtubules in vitro, but these
      microtubules do not self-organize in the ordered patterns observed at 1g.
      Likewise, at near weightlessness cortical microtubules in protoplasts have
      difficulty organizing into parallel arrays, which are required for proper plant
      cell elongation. However, intact plants do grow in space and therefore should
      have a normally functioning microtubule cytoskeleton. Since the main difference
      between protoplasts and plant cells in a tissue is the presence of a cell wall,
      we studied single, but walled, tobacco BY-2 suspension-cultured cells during an 8
      day space-flight experiment on board of the Soyuz capsule and the International
      Space Station during the 12S mission (March-April 2006). We show that the
      cortical microtubule density, ordering and orientation in isolated walled plant
      cells are unaffected by near weightlessness, as are the orientation of the
      cellulose microfibrils, cell proliferation, and cell shape. Likely, tissue
      organization is not essential for the organization of these structures in space.
      When combined with the fact that many recovering protoplasts have an aberrant
      cortical microtubule cytoskeleton, the results suggest a role for the cell wall,
      or its production machinery, in structuring the microtubule cytoskeleton.

PMID- 19756726
TI  - Tissue transglutaminase expression in celiac mucosa: an immunohistochemical
      study.
AB  - Tissue transglutaminase (tTG) constitutes the main autoantigen in celiac disease
      (CD). The aim of the study was to clarify weather celiac disease is associated
      with changes in tTG expression in duodenal mucosa. Tissue transglutaminase was
      assessed immunohistochemically (clone CUB 7402) in duodenal biopsy specimens from
      22 untreated CD patients, ten normal controls (NC) with unremarkable duodenal
      mucosa, and nine disease nonceliac controls (DC). In 15 CD patients duodenal
      biopsy specimens were repeatedly assessed after these patients had been
      prescribed gluten-free diet. Positive pixel count algorithm of ImageScope was
      used for quantitative evaluation of immunohistochemistry. Tissue transglutaminase
      expression in superficial epithelium differed significantly between the three
      groups (p < 0.001). It was increased in DC in relation to NC (p < 0.001) and in
      CD--in relation to NC (p < 0.001) and DC (p = 0.003). In CD and DC, cryptal
      epithelium was stained more intensively than in NC (p < 0.001), but there was no
      difference between CD and DC (p = 0.507). The same pattern was seen in lamina
      propria. A significant decrease in tTG expression in all the compartments was
      seen in repeatedly assessed samples. Untreated CD is associated with tTG
      overexpression, which is reversible. Tissue transglutaminase up-regulation does
      not seem to be specific for CD and can appear in other pathological conditions.

PMID- 19756727
TI  - Intestinal type of mucinous borderline tumor arising from mixed epithelial and
      stromal tumor of kidney.
AB  - We report a mucinous borderline tumor arising from a mixed epithelial and stromal
      tumor of left kidney (MESTK). The patient was an 82-year-old woman who presented
      with gross hematuria and recurrent urinary tract infection for years. The patient
      had a cytoscopy with a retrograde pyelogram, which indicated a dilated left
      kidney with a central mass lesion. Subsequently, she underwent a radical left
      nephrectomy. Cross-sections of left kidney showed a 4.5 x 3.5 x 1.5 cm ill
      defined cystic lesion with mucinous and solid areas. Histologic sections of the
      lesion showed numerous variable-sized dilated cysts with fibrous, fatty,
      vascular, and smooth muscle stroma. The cysts were lined by a various types of
      epithelium, including single layer of flat, cuboidal and mucinous epithelium,
      urothelium, intestinal epithelium, and endocervical epithelium. In areas, the
      mucinous epithelium showed complex proliferation with stratification, papillae
      formation, and nuclear atypia, resembling that of an ovarian mucinous borderline
      tumor, a colorectal tubular adenoma, or a low-grade appendiceal mucinous
      carcinoma. Immunohistochemically, the mucinous borderline tumor showed a
      colorectal phenotype, being strongly positive for CK20, CDX-2, and MUC2. There
      was no invasive mucinous tumor identified. We believe that this case represents
      the first reported example of mucinous borderline tumor arising from a MESTK.

PMID- 19756728
TI  - Spectrum of congenital heart defects in Croatia.
AB  - The aim of our study was to investigate the incidence of congenital defects in
      children born in Croatia during a period of 5 years, its association with
      extracardiac malformations, its treatment, and outcome. Medical information about
      the patients was obtained from 14 paediatric cardiology centres that cover the
      whole country. Diagnosis was made by clinical findings, electrocardiography,
      chest X-ray, echocardiography, catheterisation, or autopsy. Between October 1,
      2002 and October 1, 2007, there were 205,051 live births in Croatia, 1,480 of
      which were patients diagnosed with congenital heart disease, accounting for 0.72%
      of the live-born children. The distribution was made up of 34.6% children with
      ventricular septal defect, 15.9% with atrial septal defect, 9.8% with patency of
      arterial duct, 4.9% with pulmonary valvar stenosis, 3.3% with tetralogy of
      Fallot, 3.3% with transposed great arteries, 3.3% with aortic stenosis, 3.2% with
      aortic coarctation, 4.3% with atrioventricular septal defect and common
      atrioventricular orifice, 2.3% with hypoplastic left heart syndrome, and 8.3%
      other with severe defects. The average age in the time of diagnoses is 70.41 days
      (SD, 188.13), with low average time of diagnoses of severe heart defects, 9.6
      days (SD, 32.52). Among patients, 14.5% had chromosomal defects, syndromes,
      and/or other congenital major anomalies. During the study, 57 patients died
      because of cardiac anomalies or other related problems, 24 who died were
      operated. The rates of specific cardiac defects and association with extracardiac
      malformations are generally comparable with those reported in similar studies. In
      spite of all problems, mortality rate of 3.85% is low but could be improved.

PMID- 19756729
TI  - Sclerosing cholangitis and combination antifungal therapy for PNP deficiency
      patients.

PMID- 19756730
TI  - Does the severity of congenital heart defects affect disease-specific health
      related quality of life in children in Bosnia and Herzegovina?
AB  - The aim of this study was to assess whether the severity of congenital heart
      defects (CHD) affects disease-specific health-related quality of life (HRQOL) in
      children after open heart surgery. One hundred and fourteen children with CHD and
      one of their parents participated in the study. HRQOL was evaluated by the PedsQL
      3.0 Cardiac Module. The children were assigned to one of three groups according
      to severity of CHD. Children with cyanotic CHD (Group 3) reported that their
      HRQOL on several domains was lower than that of children with anomalies with the
      left-right shunt and children with obstructive anomalies. Also, by parent proxy
      report, patients with anomalies with the left-right shunt had statistically
      significant, better HRQOL scores for the heart problems and treatment scales,
      perceived physical appearance, treatment anxiety, cognitive problems, and
      communication scales in comparison to the children with cyanotic CHD. By self
      report, children of Group 1 reported that they had statistically significant,
      better HRQOL in the heart problems and treatment scales compared with Group 2.
      CONCLUSIONS: The results of the assessment by the PedsQL 3.0 Cardiac Module, a
      cardiac disease-specific instrument for children with CHD, indicate that HRQOL is
      poorest in children with complex CHD. Therefore, it is necessary to take the
      appropriate preventive measures for these patients, which include early (timely)
      cardiosurgical intervention and active psychological support to limit the
      negative impact of serious forms of CHD on the quality of life of these children.

PMID- 19756731
TI  - Familial primary carpal tunnel syndrome with possible skipped generation.
AB  - Carpal tunnel syndrome, an entrapment neuropathy of the median nerve, is rarely
      seen in childhood. Familial carpal tunnel syndrome, an even more exceptional
      entity, is frequently associated with inherited systemic disorders. Rarely it can
      be presented as a primary familial form with Mendelian autosomal dominant
      inheritance. We report the occurrence of carpal tunnel syndrome in two
      generations of a family in which the index case was a 6-year-old boy with
      bilateral hand pain and paresthesias. Our report demonstrates an interesting
      inheritance pattern of carpal tunnel syndrome in a family transmitted by an
      autosomal dominant gene with variable expressivity and reduced penetrance. To our
      knowledge, it is the first report of familial bilateral carpal tunnel syndrome in
      a family with possible skipped generation.

PMID- 19756732
TI  - Prevalence of flexible flatfoot in Taiwanese school-aged children in relation to
      obesity, gender, and age.
AB  - The objective of this study was to determine the prevalence of flexible flatfoot
      in elementary school children in Taiwan and evaluate the relationship between
      flatfoot and obesity, gender, and age. A sample of 2,083 children, between 7 and
      12 years of age from public elementary schools in northern Taiwan was analyzed.
      Children were stratified into groups according to age: 7, 8, 9, 10, 11, or 12
      years old. Demographic information was obtained, and the presence of flatfoot
      determined by footprint analysis and grading according to Denis flatfoot staging.
      A total of 1,222 (59%) children were documented with flatfoot. The incidence
      percentages of flatfoot were: 67% of males, 49% of females, and 75%, 65%, 57%,
      and 48% of obese, overweight, normal weight, and underweight children,
      respectively. A preponderance of flatfoot was observed among 8-year-olds.
      Multivariate analyses indicated that 8- and 9-year-olds were 1.52 and 0.72 times
      more likely to have flatfoot than 7-year-olds. Males were twice as likely to have
      flatfoot as females. Children who were obese or overweight were 2.66 and 1.39
      times more likely to have flatfoot than those of average weight. The results of
      this study indicate that the prevalence of flexible flatfoot is highest among
      males who are obese and overweight, particularly in the age range of 7 to 8
      years.

PMID- 19756733
TI  - Behcet disease: treatment of vascular involvement in children.
AB  - Behcet disease is the only primary vasculitis that affects both arteries and
      veins of any size. We present our treatment protocol in disease with vascular
      involvement in seven pediatric patients. All seven patients met the international
      criteria for the disease before the age of 16 years. Only one was a girl. The
      vascular involvement was as follows: Two patients had superficial vein
      thrombosis, two patients had atrial or ventricular thrombosis, one had arterial
      involvement with pulmonary aneurysms, and two had thrombosis of the venous
      sinuses in the central nervous system. The median duration of vascular
      involvement was 4 months (range 3-24 months) after the diagnosis of BD and was
      concomitant with diagnosis in three patients. All received colchicine and
      steroids. The ones with thrombosis in the venous system received additional
      azathioprine, whereas those with pulmonary arterial or cardiac involvement
      initially received cyclophosphamide for 150-180 mg/kg total dose (IV or oral) and
      then were switched to azathioprine for a further 6 months. All except the patient
      with pulmonary arterial involvement received a course of anticoagulation
      treatment as well. These patients have been followed up for a period of at least
      18 months and so far are free of vascular relapses. One has developed a severe
      uveitis necessitating further therapy. In conclusion, features of vascular
      involvement should be carefully sought for in patients with Behcet disease.
      Effective management has enabled disease-free survival in the presented patients.

PMID- 19756734
TI  - Identification of potential serum markers for endometrial cancer using protein
      expression profiling.
AB  - OBJECTIVES: Screening method of endometrial cancer (EC) has not been established
      yet. Our study was to explore serum biomarkers of EC patients using surface
      enhanced laser desorption and ionization-time-of-flight mass spectrometry (SELDI
      TOF MS). METHODS: Serum samples from 65 EC patients and 40 controls were analyzed
      by SELDI-TOF MS (training set). Single- and multi-variant analyses were performed
      to compare protein profiles in serum of EC patients and healthy controls.
      Subsequently, blind test set including 40 EC patients and 40 controls were
      analyzed for validation. RESULTS: A panel of four biomarker candidates were
      selected in training set analysis. These markers could also distinguish stage I
      patients from controls. Among them, two biomarkers were purified and identified
      as apolipoprotein A1 and a modified form of apolipoprotein C1. Screening for
      blind test set using dual-biomarker analysis yielded a sensitivity of 82% and a
      specificity of 86%. CONCLUSIONS: Involvement of apolipoproteins with EC is first
      suggested in this study. In addition to possibility of screening method for EC,
      findings of these new biomarkers might be related with carcinogenesis or
      predisposition to EC.

PMID- 19756735
TI  - Mina53, a novel c-Myc target gene, is frequently expressed in lung cancers and
      exerts oncogenic property in NIH/3T3 cells.
AB  - PURPOSE: Mina53, whose expression is directly induced by c-Myc, is overexpressed
      in various cancers and plays an important role in cell growth. To clarify the
      involvement of Mina53 in lung cancers, we investigated its expression in human
      lung cancer tissues as well as in various lung cancer cell lines. METHODS: Mina53
      expression was determined by real-time RT-PCR, western blotting, and
      immunohistochemistry using lung cancer cell lines, normal human bronchial
      epithelial cells, and lung cancer tissues. Biological effects of Mina53 were
      evaluated by soft agar colony formation assay and tumorigenicity in nude mice
      using Mina53-transfected NIH/3T3 cells. cDNA microarray analysis was performed to
      determine the gene alteration by Mina53 and confirmation was made using real-time
      RT-PCR with mina53 expression plasmid or mina53 shRNA-transfected NIH/3T3 cells.
      RESULTS: We observed that 62% of patients evidenced overexpression of Mina53 from
      the early clinical stages of lung cancer. Differences according to gender,
      smoking status, or histologic type were not statistically significant. Forced
      expression of Mina53 in NIH/3T3 cells induced cell transformation, and mina53
      transfected NIH/3T3 clones produced tumors in nude mice, demonstrating that
      Mina53 has oncogenic potential. cDNA microarray revealed that 254 genes had
      altered expression in a mina53-transfected NIH/3T3 clone. Mina53 regulates
      several genes related to cell adhesion and metabolism, which have also been
      reported to be regulated by c-Myc. Genes regulated by Mina53, but not by c-Myc
      included cytokine/growth factor related genes such as EGFR, IL-6, and HGF.
      CONCLUSION: Our results suggest that Mina53 plays an important role in
      carcinogenesis and may be a target for cancer prevention.

PMID- 19756736
TI  - Serum CA 125 expression as a tumor marker for diagnosis and monitoring the
      clinical course of epithelioid sarcoma.
AB  - PURPOSE: We report here, our experience of seven patients with epithelioid
      sarcomas and their serum CA 125 levels, as well as the results of an in vitro and
      in vivo study of CA 125 expression in epithelioid sarcoma cells and xenografts
      using three epithelioid sarcoma cell lines. METHODS: In the clinical study, the
      serum CA 125 levels of seven epithelioid sarcoma patients were examined at
      multiple time points. Expression of the MUC16 gene that encodes the CA 125
      sequence was examined using RT-PCR methods in three epithelioid sarcoma cell
      lines, FU-EPS-1, SFT-8606 and NEPS, and the CA 125 protein in each cell lysate
      was examined by Western blot using anti-CA 125 clone OC125 antibody. The
      concentration of CA 125 in the conditioned medium of each cell line was also
      measured. RESULTS: In five of the seven epithelioid sarcoma patients, CA 125
      levels reflected regression and progression of their disease. The CA 125
      concentrations in the conditioned medium of FU-EPS-1, SFT-8606 and NEPS cells
      were 259, 252, and 6 U/ml, respectively. Strong expression of MUC16 mRNA was
      shown in FU-EPS-1 and SFT-8606 cells: correspondingly, a thick band was observed
      by Western blot analysis in only FU-EPS-1 and SFT-8606 cells. CONCLUSION: We
      concluded that epithelioid sarcoma cells produce and secrete CA 125 into the
      blood serum and that the elevation of serum CA 125 correlates with disease
      progression. Therefore, measuring the serum CA 125 level should provide an useful
      index for diagnosing and monitoring the course of epithelioid sarcoma.

PMID- 19756737
TI  - Co-expression of survivin, c-erbB2, and cyclooxygenase-2 (COX-2): prognostic
      value and survival of endometrial cancer patients.
AB  - AIM: The purpose of this study was to investigate the co-expression of survivin,
      c-erbB2, and COX-2 in endometrial cancer tissues and evaluate its prognostic
      significance in endometrial cancer METHODS: Tumor tissue biopsies from 110
      patients with primary untreated endometrial carcinomas were studied by
      immunohistochemistry. Statistical analysis evaluated correlation of antigen
      expression with tumor stage, grade, myometrial invasion, and histologic type.
      Association with disease outcome was also investigated RESULTS: The results
      showed that expression of the three antigens was independently associated with
      histological grade, disease stage, and myometrial invasion. Clinicopathological
      parameters were also associated with the number of antigens expressed by each
      tumor, the expression of more antigens correlating with advanced stage disease
      and deep myometrial invasion. In a 10-year follow-up, patients with tumors
      expressing more of these three antigens had significantly lower survival rate
      that those with smaller expression score CONCLUSIONS: Our results indicate that
      the co-expression score has independent prognostic value for endometrial cancer.

PMID- 19756738
TI  - In vitro and in vivo documentation of quantum dots labeled Trypanosoma cruzi-
      Rhodnius prolixus interaction using confocal microscopy.
AB  - Semiconductor quantum dots (QDs) are highly fluorescent nanocrystals markers that
      allow long photobleaching and do not destroy the parasites. In this paper, we
      used fluorescent core shell quantum dots to perform studies of live parasite
      vector interaction processes without any observable effect on the vitality of
      parasites. These nanocrystals were synthesized in aqueous medium and
      physiological pH, which is very important for monitoring live cells activities,
      and conjugated with molecules such as lectins to label specific carbohydrates
      involved on the parasite-vector interaction. These QDs were successfully used for
      the study of in vitro and in vivo interaction of Trypanosoma cruzi and the
      triatomine Rhodnius prolixus. These QDs allowed us to acquire real time confocal
      images sequences of live T. cruzi-R. prolixus interactions for an extended
      period, causing no damage to the cells. By zooming to the region of interest, we
      have been able to acquire confocal images at the three to four frames per second
      rate. Our results show that QDs are physiological fluorescent markers capable to
      label living parasites and insect vector cells. QDs can be functionalized with
      lectins to specifically mark surface carbohydrates on perimicrovillar membrane of
      R. prolixus to follow, visualize, and understand interaction between vectors and
      its parasites in real-time.

PMID- 19756739
TI  - Multiplex PCR system for identifying the carnivore origins of faeces for an
      epidemiological study on Echinococcus multilocularis in Hokkaido, Japan.
AB  - A multiplex PCR system was developed to identify the carnivore origins of faeces
      collected in Hokkaido, Japan, for epidemiological studies on Echinococcus
      multilocularis. Primers were designed against the D-loop region of mitochondrial
      DNA. Two separate primer mixtures (mix 1, specific forward primers to fox,
      raccoon dog and dog, and a universal reverse primer [prH]; and mix 2, specific
      forward primers to cat, raccoon and weasels and prH) were used so that the PCR
      products (160 bp, fox and cat; 240 bp, raccoon dog and raccoon; and 330 bp, dog
      and weasel) were distinguished by size. The multiplex PCR exhibited no cross
      reactivity between carnivore species and did not amplify DNA from rodent prey.
      When 270 field-collected faeces were examined, 250 showed single PCR products
      belonging to specific target sizes, suggesting successful carnivore
      identification for 92.6% of samples. Taeniid eggs were detected in 11.1% of
      samples and coproantigen in 30.4%; whereas the prevalences of taeniid eggs and
      coproantigen were 12.9% and 34.0% in fox faeces, and 0% and 26.3% in cat faeces,
      respectively. These results suggest that the prevalence in different target
      animals can be evaluated individually and precisely using multiplex PCR system.

PMID- 19756740
TI  - Japanese monkey (Macaca fuscata) with alveolar echinococcosis after treatment
      with albendazole for 10 years: serodiagnosis and determination of albendazole
      metabolites.
AB  - In 1997, an outbreak of alveolar echinococcosis in Japanese monkeys (Macaca
      fuscata) occurred in a zoo in Hokkaido, Japan. Twelve infected monkeys from a
      colony (n = 57) were diagnosed serologically by Western blotting, and
      ultrasonography showed the presence of tumor-like tissue in the livers of nine
      monkeys. The 12 infected monkeys have been treated with albendazole for 10 years
      without surgical resection. Ten of these monkeys have died so far; diagnoses were
      confirmed histopathologically through autopsy. Two of these monkeys are still
      alive. Recently, a significant difference between the two living monkeys was
      recognized. A difference in curative effect was demonstrated between the two
      living monkeys by radiography, contrast enhanced computed tomography, and
      contrast ultrasound. One showed metastasis to various organs, and the other
      appeared to be almost cured, as demonstrated by size reduction and calcification
      of the lesion after albendazole treatment for 10 years. This time, serological
      reexamination was performed to corroborate this apparent difference. The
      serological tests supported the preliminary imaging findings. In addition, the
      presence of albendazole metabolites in sera was confirmed by high-performance
      liquid chromatography. In this study, it was demonstrated that tests which have
      been used in human cases were also effective for diagnosing alveolar
      echinococcosis and for assessing curative effects in nonhuman primates such as M.
      fuscata.

PMID- 19756741
TI  - Field validation of a competitive ELISA for detection of Theileria annulata
      infection.
AB  - In previous studies, Theileria annulata surface protein (TaSP) was identified as
      an immunodominant antigen and successfully used to develop a recombinant-protein
      based indirect enzyme-linked immunosorbent assay (ELISA) for the detection of
      circulating antibodies in serum of T. annulata-infected animals. To increase the
      specificity, a competitive ELISA (cELISA) was developed using recombinant TaSP
      antigen and a monoclonal antibody (1C7) specifically binding to TaSP. Since the
      cELISA accurately differentiated T. annulata-infected from uninfected animals, a
      study was performed to analyse the suitability of the cELISA in the field. For
      this, 230 sera with unknown status from different governorates in the north of
      Iraq were analysed using both the indirect and competitive ELISA and were
      compared. There was a significant (p < 0.5 x 10(-19)) correlation (r = 0.556)
      between the tests, whereby the cELISA detected more sera as negative (44/230)
      compared to the indirect ELISA (21/270). Accordingly, less sera were determined
      to be positive in the competitive (186/230) than in the indirect ELISA (209/230).
      Sensitivity and specificity of the cELISA taking the indirect ELISA as a
      reference were 84.2% and 52.4%, respectively. Accordingly, the calculated
      prevalence of T. annulata infection was 90.9%, and the positive predictive value
      was determined to be 94.6%. Taken together, the cELISA proved its suitability for
      field application and was found qualified for use in serological surveys to
      monitor the prevalence of T. annulata infection and to identify carrier animals.

PMID- 19756742
TI  - Newly acquired Onchocerca volvulus filariae after doxycycline treatment.
AB  - Despite successful mass drug administration and vector control programs, the
      nematode Onchocerca volvulus is far from being eradicated. Therefore, new long
      term sterilizing or macrofilaricidal drugs are needed. The depletion of Wolbachia
      endobacteria using doxycycline leads to long-term sterilizing effects and
      macrofilaricidal activity against female filariae of more than 60%. The worms die
      or degenerate 18-27 months after doxycycline. However, during this time patients
      may be exposed to new infections. We evaluated these newly acquired worms in
      onchocercomas of doxycycline-treated patients in relation to transmission using
      morphology, histochemistry, and immunohistology. On an average, 10% of the female
      filariae had been newly acquired per year in the treated groups. Our observations
      showed: (a) Sixty-three of 68 newly acquired worms harbored many intact
      Wolbachia, whereas none of the other surviving worms contained many bacteria. (b)
      Higher percentages of dead filariae than originally reported were calculated,
      when the new worms were excluded, indicating a stronger macrofilaricidal activity
      than previously reported. The difference was significant for female filariae
      after doxycycline treatment for 6 weeks. (c) Only newly acquired worms presented
      normal embryogenesis and microfilariae production after sufficient treatment. We
      conclude that newly acquired filariae have to be considered when evaluating drug
      efficacy in onchocerciasis.

PMID- 19756743
TI  - Coevolution between multiple helminth infestations and basal immune investment in
      mammals: cumulative effects of polyparasitism?
AB  - Animals often suffer from multiple parasite attacks in natural conditions (i.e.,
      polyparasitism). The community of these parasites, which simultaneously or
      sequentially infest given host species, has rarely been investigated as a
      parasitic pressure per se. From this perspective, and despite the impressive
      number of immunoecological or comparative studies, the impacts of polyparasitism
      on immune responses are far from being appreciated. Focusing on helminths across
      a wide range of mammalian species and using a phylogenetic comparative method, we
      show, for the first time, that an increase in the number of helminth parasite
      species is positively correlated with an increase in basal immune investment
      (estimated by the counts of white blood cells) across mammal species. After
      discussing inherent limits of this comparative approach, we put this result in
      the evolutionary perspective of multiple parasitic infestations.

PMID- 19756744
TI  - Experimental model in rats for study on transmission dynamics and evaluation of
      Clonorchis sinensis infection immunologically, morphologically, and
      pathologically.
AB  - This study aims to gain a better insight into the transmission patterns and
      immunologic profile of Clonorchis sinensis infection and make a headway on the
      pathogenesis regarding cholangiocarcinoma and hepatic lesions. Experimental
      models orally infected by C . sinensis metacercariae were constructed in rats.
      Immunological assays were performed to measure serum level of IgA, IgE, IgG1,
      IgG2a, IFN-gamma, and IL-4. Infection parameters were assessed by worm recovery
      rate, eggs per gram faece and worm size. Pathological sections with livers were
      managed with immunofluorescence, hematoxylin, eosin, and Masson's trichrome
      staining to evaluate the hepatic pathological changes. Interestingly, rats
      infected with only one C . sinensis metacercariae even gained a high worm
      recovery rate of 83.3% compared with rats infected with more metacercariae.
      Serological changes according to different infection doses indicated that immune
      response presented a tendency to Th2 type by expressing transient high level of
      IgG1, IL-4, and IgE. Hepatic tissues appeared inflammatory and fibrotic, revealed
      by different stainings. Intrahepatic bile ducts displayed cholangiectasis and
      proliferation with excreted/secreted antigen histologically located. C .
      sinensis, as a fish-borne zoonosis, presented novel transmission patterns which
      explained high infection rate in endemic areas; infection rate of C . sinensis
      was frequency-dependent and dose-related. Humoral immunity played a prevalent
      role in resisting to C . sinensis based on the rat models. C . sinensis infection
      played an undoubted role in biliary and hepatic diseases.

PMID- 19756745
TI  - Life cycle of Ixodes luciae (Acari: Ixodidae) in the laboratory.
AB  - The life cycle of Ixodes luciae was evaluated for five consecutive generations in
      the laboratory. Wild mice Calomys callosus and laboratory rats Rattus norvegicus
      were used as hosts for larvae and nymphs. For adult ticks, opossums Didelphis
      aurita were used as hosts. Off-host developmental periods were observed in an
      incubator at 27 degrees C and 95% RH. The life cycle of I. luciae lasted 95-97
      days, excluding prefeeding periods. C. callosus, one of the natural host species
      for I. luciae immature stages, was shown to be much more suitable than the
      artificial host R. norvegicus. Significantly (P < 0.05), more larvae and nymphs
      successfully fed on C. callosus than on R. norvegicus. When tick-naive C.
      callosus were exposed to three consecutive larval infestations at 24-day
      intervals, recovery of engorged larvae were greater in the second and third
      infestations, indicating that previous infestations did not induce acquired
      resistance to ticks. Larval feeding period typically varied from 5 to 10 days on
      R. norvegicus, but was significantly (P < 0.05), longer on C. callosus (range, 7
      34 days). The majority (71.7%) of I. luciae adult females successfully fed and
      oviposited after exposed to D. aurita. Mean engorged weight (581.9 mg; range,
      237.1-796.0 mg) of these females were much higher than those previously reported
      for other New World Ixodes species. Our results are in accordance to the current
      literature that appoints opossums Didelphidae and small rodents (e.g., C.
      callosus) natural hosts for I. luciae immature and adult stages, respectively.

PMID- 19756746
TI  - Molecular cloning, sequencing, and expression analysis of presenilin cDNA from
      Schistosoma mansoni.
AB  - Presenilins (PS) are integral membrane proteins involved, among other functions,
      in regulated intramembrane proteolysis. In this study, we report the
      identification and characterization of a complementary DNA from Schistosoma
      mansoni exhibiting a significant homology to human and nonvertebrate presinilins.
      S. mansoni contained a 1,485 bp open reading frame encoding a predicted protein
      of 494 amino acids. Alignment of predicted amino acid sequence of S. mansoni with
      PS (SmPS) from other species revealed up to 40% similarity shared among the
      investigated organisms. In addition, phylogenetic analyses demonstrated SmPS
      being closely related to its orthologues found in Schistosoma japonicum and
      Caenorhabditis elegans. Expression analysis of SmPS using quantitative real-time
      PCR revealed that the transcript is up-regulated in the egg stage. We hypothesize
      that the high level of SmPS in the S. mansoni embryo correlates to an important
      role during cellular signaling associated to larval development. To our
      knowledge, this study represents the first attempt to investigate the existence
      and abundance of PS from a helminth parasite.

PMID- 19756747
TI  - Steroid hormones alter AMP hydrolysis in intact trophozoites of Trichomonas
      vaginalis.
AB  - Trichomonas vaginalis infection may be influenced by the vaginal concentrations
      of estrogens. We have investigated the effects of 17beta-estradiol and
      dehydroepiandrosterone sulfate (DHEAS) on the ecto-5'-nucleotidase activity in
      fresh clinical (VP60) and in long-term-grown (30236 ATCC) isolates of T.
      vaginalis. In vitro exposure to DHEAS and 17beta-estradiol did not induce any
      changes in adenosine monophosphate (AMP) hydrolysis in these isolates. The
      treatment of parasites in the presence of DHEAS (0.01-1.0 microM) for 2 h
      inhibited AMP hydrolysis in VP60 isolate, whereas there were no significant
      changes in nucleotide hydrolysis in the presence of 17beta-estradiol. DHEAS and
      17beta-estradiol (0.01-1.0 microM) for 2 h inhibited AMP hydrolysis in 30236
      isolate. The 12 treatment with 0.1 microM DHEAS inhibited AMP hydrolysis, whereas
      17beta-estradiol did not alter the nucleotide hydrolysis in VP60 isolate. Our
      findings have shown that the complex effect of steroid hormones and their
      receptors on T. vaginalis may promote changes in ecto-5'-nucleotidase activity
      during exposure to these hormones.

PMID- 19756748
TI  - Ex vivo and in vivo biological behavior of Leishmania (Viannia) shawi.
AB  - Since the first description of Leishmania (Viannia) shawi, few studies were
      performed with this parasite. In the present work, the in vivo and ex vivo
      behavior of L. (Viannia) shawi infection was studied using murine model.
      Peritoneal macrophages from BALB/c and C57BL/6 mice were infected with
      promastigotes in the stationary phase of growth; after 24 h, the infection index
      and nitric oxide (NO) levels in the supernatant of the cultures were analyzed.
      BALB/c and C57BL/6 mice were infected into the hind footpad, and at each 2 weeks,
      mice were sacrificed, and the histological changes of the skin inoculation site,
      parasitism, and humoral immune responses were evaluated during 8 weeks. Ex vivo
      experiments showed that macrophages of BALB/c presented higher infection index
      and lesser NO levels than macrophages of C57BL/6. In vivo experiments showed that
      BALB/c presented higher lesion size than C57BL/6 mice; similarly, the
      histopathological changes and the parasitism in skin were more exacerbate in
      BALB/c mice. In draining lymph nodes, the main change was increase of germinative
      centers, and parasites were detected from 6 weeks pi onwards in both mice strain.
      IgG was detected in BALB/c mice from 4 weeks, while in C57BL/6, from 6 weeks pi
      onwards. Taken together, these results indicate that BALB/c showed a classical
      behavior of susceptibility when compared to C57BL/6 mice.

PMID- 19756749
TI  - Biological control of sheep gastrointestinal nematodiasis in a tropical region of
      the southeast of Brazil with the nematode predatory fungi Duddingtonia flagrans
      and Monacrosporium thaumasium.
AB  - Formulations in matrix of sodium alginate (pellets) of the nematode predatory
      fungi Duddingtonia flagrans and Monacrosporium thaumasium were evaluated in the
      biological control of sheep gastrointestinal nematodiasis. Three groups (1, 2,
      and 3), each one with eight sheep of the Santa Ines breed, at the ages of 15-48
      months, were placed in paddocks of Brachiaria decumbens for 5 months. In group 1,
      each animal received 1 g/10 kg of live weight (l.w.) of pellets of D. flagrans
      (0.2 g of fungus/10 kg l.w.). In group 2, each animal received 1 g/10 kg of l.w.
      of pellets of the fungus M. thaumasium (0.2 g of fungus/10 kg l.w.), twice a
      week, for 5 months. In group 3 (control), the animals received 1 g/10 kg of live
      weight of pellets without fungus. The monthly averages of the egg countings per
      gram of feces of the animals of groups 1 and 2 treated were 71.6% and 61.1%
      smaller, respectively, in comparison to the animals of group 3 (control). The
      treatment of sheep with pellets containing the nematophagous fungi D. flagrans
      and M. thaumasium may be used as an alternative for the control of sheep
      gastrointestinal nematodiasis.

PMID- 19756750
TI  - Histopathological alteration of juvenile Schistosoma japonicum in mice following
      treatment with single-dose mefloquine.
AB  - This study aims to observe the histopathological alterations in schistosomula of
      Schistosoma japonicum induced by mefloquine. Mice were infected with S. japonicum
      cercariae, and after 14 days, a single dose of mefloquine (400 mg/kg) was
      administered orally. After 8 h, 24 h, 3 days, 7 days, and 14 days, groups of two
      to three mice were sacrificed, and livers were removed, fixed and processed
      routinely, and examined by light microscopy. After 8 h, 51.5% of the
      schistosomula examined showed degeneration, which included high dilatation of
      gut, desquamation of gut epithelial cells, swelling of tegument, muscles, and
      parenchymal tissues, and adherence of inflammatory cells to the damaged tegument
      of the juveniles. After 24 h, the percentage of dead worm and degenerated worm
      were 43.2% and 48.4%, respectively, and the intensity of damage increased,
      including severe swelling and vesiculation of tegument, collapse of damaged gut,
      and loss of definition in the internal structure. In addition, dead worms were
      infiltrated by eosinophil-predominated inflammatory cells. After 3 days, more
      than 96% of schistosomula were severely degenerated and dead, and some of them
      were focally or extensively infiltrated by inflammatory cells accompanied by
      necrosis of internal structure. Seven to 14 days after treatment, most dead
      schistosomula developed to dead worm granulomas with the percentages of 60.1
      86.3%, while those of dead schistosomula were 26.7-8.4%. The results indicate
      that mefloquine exhibits an extensive and severe damage to juvenile S. japonicum
      harbored in mice.

PMID- 19756751
TI  - Immunodominant antigens in Naegleria fowleri excretory--secretory proteins were
      potential pathogenic factors.
AB  - Naegleria fowleri, a ubiquitous pathogenic free-living amoeba, is the most
      virulent species and causes primary amoebic meningoencephalitis in laboratory
      animals and humans. The parasite secretes various inducing molecules as
      biological responses, which are thought to be involved in pathophysiological and
      immunological events during infection. To investigate what molecules of N.
      fowleri excretory-secretory proteins (ESPs) are related with amoebic
      pathogenicity, N. fowleri ESPs fractionated by two-dimensional electrophoresis
      were reacted with N. fowleri infection or immune sera. To identify immunodominant
      ESPs, six major protein spots were selected and analyzed by N-terminal
      sequencing. Finally, six proteins, 58, 40, 24, 21, 18, and 16 kDa of molecular
      weight, were partially cloned and matched with reference proteins as follow: 58
      kDa of exendin-3 precursor, 40 kDa of secretory lipase, 24 kDa of cathepsin B
      like proteases and cysteine protease, 21 kDa of cathepsin B, 18 kDa of
      peroxiredoxin, and 16 kDa of thrombin receptor, respectively. These results
      suggest that N. fowleri ESPs contained important proteins, which may play an
      important role in the pathogenicity of N. fowleri.

PMID- 19756752
TI  - Cloning, characterization, and expression of a novel secretory lipase-like gene
      from Clonorchis sinensis.
AB  - A secretory lipase-like gene was isolated from total cDNA of adult Clonorchis
      sinensis. The gene has an open reading frame of 1,218 bp long and encodes for a
      protein of 406 amino acids including a putative signal peptide of 20 amino acids.
      The deduced amino acid sequence including signal peptide has 42-45% identity with
      lipase of other species and two typical enzymic active sites that contain
      consensus sequence (Gly-X-Ser-X-Gly) of lipase. The cDNA encoding this protein
      was subcloned into pET-28a (+) expression vector and expressed in Escherichia
      coli. The expressed fusion protein has a molecular mass of about 45 kDa.
      Prediction of signal peptide and Western blot analysis indicated that the
      secretory lipase-like protein is an excretory-secretory product of C. sinensis.
      Immunostaining revealed that the secretory lipase-like protein was localized in
      the tegument of the adult worm and metacercaria. These results provide basis for
      further studies on the nutrition taking and invasion of C. sinensis mediated by
      the secretory lipase-like protein.

PMID- 19756754
TI  - Basement membranes and human disease.
AB  - In 1990, the role of basement membranes in human disease was established by the
      identification of COL4A5 mutations in Alport's syndrome. Since then, the number
      of diseases caused by mutations in basement membrane components has steadily
      increased as has our understanding of the roles of basement membranes in organ
      development and function. However, many questions remain as to the molecular and
      cellular consequences of these mutations and the way in which they lead to the
      observed disease phenotypes. Despite this, exciting progress has recently been
      made with potential treatment options for some of these so far incurable
      diseases.

PMID- 19756753
TI  - Immunogenicity of self-adjuvanticity oral vaccine candidate based on use of
      Bacillus subtilis spore displaying Schistosoma japonicum 26 KDa GST protein.
AB  - One of the promising approaches in mucosal immunization relies on live
      recombinant vaccine carriers. In this study, we used a six-extracellular protease
      deficient Bacillus subtilis strain WB600 to express Schistosoma japonicum 26 kDa
      glutathione S-transferase (GST). Western blot, immunofluorescence, and flow
      cytometry analyses were used to identify SjGST expression on spore surface. SjGST
      recombinant spores were used for oral vaccination in mice and were shown to
      generate mucosal and systemic response. Both SjGST-specific secretory IgA in
      feces and IgG in serum augmented significantly on day 33 after oral
      administration. It seemed that surface display of recombinant S. japonicum SjGST
      on B. subtilis WB600 spores showed good immunogenicity, and B. subtilis spores
      could be used as potential mucosal delivery vehicles to provide more effective
      vaccination strategies for parasite prevention and control in the future.

PMID- 19756755
TI  - Mutual regulation of the Drosophila disconnected (disco) and Distal-less (Dll)
      genes contributes to proximal-distal patterning of antenna and leg.
AB  - The Drosophila disconnected (disco) gene encodes a C(2)H(2)-type zinc finger
      transcription factor required for the development of the central and peripheral
      nervous systems. We report that disco participates in a positive feedback loop
      with the Dll gene, a master regulator of ventral appendage development. Dll
      function is not only required for proper disco expression in antenna and leg
      discs, but is also sufficient for ectopic expression of disco in the developing
      retina and wing imaginal discs. Conversely, disco gene function is required for
      the maintenance of Dll expression. We show that Dll phenotypes are partially
      rescued by the up-regulation of disco expression in the Dll domain. Reduction in
      disco gene function disrupts antenna and leg development, and the phenotypes
      closely resemble that produced by Dll alleles. These observations demonstrate
      that disco plays a fundamental role in the Dll-dependent patterning of antenna
      and leg, perhaps as a regulator of Dll gene expression.

PMID- 19756756
TI  - Suprastructures of extracellular matrices: paradigms of functions controlled by
      aggregates rather than molecules.
AB  - Extracellular matrices (ECM) not only serve as structural scaffolds in organs and
      tissues, but also determine critical cellular functions through cell-matrix
      interactions. These are mediated by cell surface receptors that recognise
      specific structural features of ECMs and, hence, overall physical properties of
      the acellular environment. ECM structures are subject to hierarchic
      organisations, which are tightly adapted to the functions of tissues and organs.
      Only a few specialised tasks are reserved for isolated ECM macromolecules.
      Instead, molecular ECM components attain their prominent functions only after
      polymerising into insoluble suprastructural elements, i.e. fibrils, microfibrils,
      or networks that, in turn, are assembled into regional tissue structures, such as
      fibres or basement membranes. As an outstanding feature, most, if not all, ECM
      suprastructures are co-polymers of more than one molecular species that differ in
      their identity and relative abundance. Thus, ECM suprastructures are composite
      biological amalgamates. The analogy to metal alloys refers to structural and
      functional characteristics of ECM composites, which differ from those of each
      homo-polymeric aggregate. At the tissue level, biological alloys can themselves
      be assembled into conglomerates that again assume properties distinct from those
      of each individual alloy. Nevertheless, most studies in matrix biology solely
      focus on molecular features and mechanisms. Progress has however been made in
      identifying principles of interactions within suprastructural elements and their
      functional consequences. We are now only beginning to understand the impact of
      suprastructural organisation on the assembly and the functions of whole tissues
      and many fundamental issues in this almost pristine field await discovery.

PMID- 19756757
TI  - Mouse Odf2 localizes to centrosomes and basal bodies in adult tissues and to the
      photoreceptor primary cilium.
AB  - Odf2 (outer dense fiber 2) is the major protein of the cytoskeleton of the sperm
      tail. In somatic cells, it is a component of the centrosome in which it is
      located in the appendages of the mother centriole. Additionally, as shown
      previously by forced expression in cultured cells, Odf2 localizes to centrioles,
      basal bodies, and primary cilia, which are all structurally and functionally
      interconnected. The importance of Odf2 has become obvious by the absence of
      primary cilia in Odf2-deficient cells and by the embryonic lethality of the Odf2
      gene trap insertional mouse. However, nothing is known about the endogenous
      localization of Odf2 in the tissues of adult mice. We show here that Odf2 protein
      localizes to centrosomes, to photoreceptor primary cilia, and to basal bodies of
      ciliated cells of the respiratory epithelium and of the kidney. Our results thus
      suggest that Odf2 contributes to assorted ciliopathies.

PMID- 19756758
TI  - Localization of poly(A)(+) RNA and mRNA export factors in interchromatin granule
      clusters of two-cell mouse embryos.
AB  - Interchromatin granule clusters (IGCs), also known as nuclear speckles, splicing
      factor compartments, or SC35-domains, are one of the most universal nuclear
      organelles of the cell. We have used two-cell mouse embryos as an experimental
      system to study the possible association of poly(A)(+) RNA and factors involved
      in RNA export (Tip-associated protein [TAP] and heterogenous nuclear
      ribonucleoprotein A/B [hnRNP A/B]) with IGCs. Poly(A)(+) RNA was localized by
      microinjections of 2'-O-Me(U)(22) probes conjugated with tetramethylrhodamine.
      RNA export proteins were detected by immunofluorescence confocal laser microscopy
      and immunogold-labeling electron microscopy. We found that poly(A)(+) RNA was
      located in IGCs regardless of the transcriptional state of the nuclei. hnRNP A/B
      was also found to characterize IGCs of the embryo nuclei with various levels of
      transcription activity. In transcriptionally active embryo nuclei, TAP was
      detected in the vicinity of IGCs rather than inside them; however, when
      transcription was inhibited by drugs, TAP was localized to IGCs. Our data support
      the idea that IGCs not only serve as splicing factor reservoirs, but also take
      part in mRNA retention and export.

PMID- 19756759
TI  - Patterns of Tamarix water use during a record drought.
AB  - During a record drought (2006) in southwest Kansas, USA, we assessed groundwater
      dynamics in a shallow, unconfined aquifer, along with plant water sources and
      physiological responses of the invasive riparian shrub Tamarix ramosissima. In
      early May, diel water table fluctuations indicated evapotranspirative consumption
      of groundwater by vegetation. During the summer drought, the water table
      elevation dropped past the lowest position previously recorded. Concurrent with
      this drop, water table fluctuations abruptly diminished at all wells at which
      they had previously been observed despite increasing evapotranspirative demand.
      Following reductions in groundwater fluctuations, volumetric water content
      declined corresponding to the well-specific depths of the capillary fringe in
      early May, suggesting a switch from primary dependence on groundwater to vadose
      zone water. In at least one well, the fluctuations appear to re-intensify in
      August, suggesting increased groundwater uptake by Tamarix or other non-senesced
      species from a deeper water table later in the growing season. Our data suggest
      that Tamarix can rapidly shift water sources in response to declines in the water
      table. The use of multiple water sources by Tamarix minimized leaf-level water
      stress during drought periods. This study illustrates the importance of the
      previous hydrologic conditions experienced by site vegetation for controlling
      root establishment at depth and demonstrates the utility of data from high
      frequency hydrologic monitoring in the interpretation of plant water sources
      using isotopic methods.

PMID- 19756760
TI  - Neighbour identity hardly affects litter-mixture effects on decomposition rates
      of New Zealand forest species.
AB  - The mass loss of litter mixtures is often different than expected based on the
      mass loss of the component species. We investigated if the identity of neighbour
      species affects these litter-mixing effects. To achieve this, we compared
      decomposition rates in monoculture and in all possible two-species combinations
      of eight tree species, widely differing in litter chemistry, set out in two
      contrasting New Zealand forest types. Litter from the mixed-species litter bags
      was separated into its component species, which allowed us to quantify the
      importance of litter-mixing effects and neighbour identity, relative to the
      effects of species identity, litter chemistry and litter incubation environment.
      Controlling factors on litter decomposition rate decreased in importance in the
      order: species identity (litter quality) >> forest type >> neighbour species.
      Species identity had the strongest influence on decomposition rate. Interspecific
      differences in initial litter lignin concentration explained a large proportion
      of the interspecific differences in litter decomposition rate. Litter mass loss
      was higher and litter-mixture effects were stronger on the younger, more fertile
      alluvial soils than on the older, less-fertile marine terrace soils. Litter
      mixture effects only shifted percentage mass loss within the range of 1.5%. There
      was no evidence that certain litter mixtures consistently showed interactive
      effects. Contrary to common theory, adding a relatively fast-decomposing species
      generally slowed down the decomposition of the slower decomposing species in the
      mixture. This study shows that: (1) species identity, litter chemistry and forest
      type are quantitatively the most important drivers of litter decomposition in a
      New Zealand rain forest; (2) litter-mixture effects-although statistically
      significant-are far less important and hardly depend on the identity and the
      chemical characteristics of the neighbour species; (3) additive effects
      predominate in this ecosystem, so that mass dynamics of the mixtures can be
      predicted from the monocultures.

PMID- 19756761
TI  - Vertebrate diets derived from trophically transmitted fish parasites in the
      Bothnian Bay.
AB  - Parasites that are transmitted through predator-prey interactions may be used as
      indicators of trophic relationships between organisms. Yet, they are rarely used
      as such in the construction of topological (predator-prey) food webs. We
      constructed food webs of vertebrate trophic interactions using observed diet
      alone, trophically transmitted parasites alone, and the combination of the two
      based on data from 31 species of fish from the Bothnian Bay, Finland. The fish
      food web contained 530 links derived from observed diet, 724 links inferred from
      parasitism, and 1,058 links calculated from a combination of both stomach
      contents and parasites. This sub-web constructed from stomach contents had a mean
      of 17.1 links per fish species, while that using parasites had 23.4 links per
      fish. Combining the two diet indicators yielded 34.1 links per fish species,
      illustrating the complementarity of the two methods. Mean number of prey species
      per fish species was 12.5 using observed diet items, 15.8 using parasites, and
      24.5 using both measures together. Mean number of predators per fish species was
      7.4 using observed diet, 11.7 using parasites and 15.0 using both. A positive
      correlation was found between the mean number of parasites and the number of prey
      taxa in the diet among the fishes. Omnivorous fish had the highest diversity of
      both parasite species and prey items, while benthophagous fish had among the
      lowest. Mean total abundance and mean total prevalence of parasites correlated
      positively with fish size, with piscivores being the largest with the highest
      abundance and prevalence, while planktivores and benthivores had the lowest.
      Trophically transmitted parasites may be used to help construct vertebrate sub
      webs and derive information about food web processes. Parasites alone provided
      equivalent if not more information than observed diet. However, resolution is
      improved by using parasites and observed diet together.

PMID- 19756762
TI  - Above- and below-ground vertebrate herbivory may each favour a different
      subordinate species in an aquatic plant community.
AB  - At least two distinct trade-offs are thought to facilitate higher diversity in
      productive plant communities under herbivory. Higher investment in defence and
      enhanced colonization potential may both correlate with decreased competitive
      ability in plants. Herbivory may thus promote coexistence of plant species
      exhibiting divergent life history strategies. How different seasonally tied
      herbivore assemblages simultaneously affect plant community composition and
      diversity is, however, largely unknown. Two contrasting types of herbivory can be
      distinguished in the aquatic vegetation of the shallow lake Lauwersmeer. In
      summer, predominantly above-ground tissues are eaten, whereas in winter,
      waterfowl forage on below-ground plant propagules. In a 4-year exclosure study we
      experimentally separated above-ground herbivory by waterfowl and large fish in
      summer from below-ground herbivory by Bewick's swans in winter. We measured the
      individual and combined effects of both herbivory periods on the composition of
      the three-species aquatic plant community. Herbivory effect sizes varied
      considerably from year to year. In 2 years herbivore exclusion in summer
      reinforced dominance of Potamogeton pectinatus with a concomitant decrease in
      Potamogeton pusillus, whereas no strong, unequivocal effect was observed in the
      other 2 years. Winter exclusion, on the other hand, had a negative effect on
      Zannichellia palustris, but the effect size differed considerably between years.
      We suggest that the colonization ability of Z. palustris may have enabled this
      species to be more abundant after reduction of P. pectinatus tuber densities by
      swans. Evenness decreased due to herbivore exclusion in summer. We conclude that
      seasonally tied above- and below-ground herbivory may each stimulate different
      components of a macrophyte community as they each favoured a different
      subordinate plant species.

PMID- 19756763
TI  - Precipitation magnitude and timing differentially affect species richness and
      plant density in the sotol grassland of the Chihuahuan Desert.
AB  - Arid and semi-arid environments are dynamic ecosystems with highly variable
      precipitation, resulting in diverse plant communities. Changes in the timing and
      magnitude of precipitation due to global climate change may further alter plant
      community composition in desert regions. In this study, we assessed changes in
      species richness and plant density at the community, functional group, and
      species level in response to variation in the magnitude of natural seasonal
      precipitation and 25% increases in seasonal precipitation [e.g., supplemental
      watering in summer, winter, or summer and winter (SW)] over a 5-year period in a
      sotol grassland in the Chihuahuan Desert. Community species richness was higher
      with increasing winter precipitation while community plant density increased with
      greater amounts of winter and summer precipitation, suggesting winter
      precipitation was important for species recruitment and summer precipitation
      promoted growth of existing species. Herb and grass density increased with
      increasing winter and summer precipitation, but only grass density showed a
      significant response to supplemental watering treatments (SW treatment plots had
      higher grass density). Shrubs and succulents did not exhibit changes in richness
      or density in response to natural or supplemental precipitation. In this 5-year
      study, changes in community species richness and density were driven by responses
      of herb and grass species that favored more frequent small precipitation events,
      shorter inter-pulse duration, and higher soil moisture. However, due to the long
      life spans of the shrub and succulent species within this community, 5 years may
      be insufficient to accurately evaluate their response to variable timing and
      magnitude of precipitation in this mid-elevation grassland.

PMID- 19756764
TI  - Pre- and postcaptopril renal scintigraphy as a screening test for renovascular
      hypertension in children.
AB  - We studied the ability of pre- and postcaptopril renal scintigraphy to predict
      renovascular disease (RVD) in children. Retrospective review of medical notes and
      radiology reports of all hypertensive children who had had both pre- and
      postcaptopril renal scintigraphy with [(99m)Tc] dimercaptosuccinic acid (DMSA)
      and/or [(99m)Tc] mercaptoacetyltriglycine (MAG3) and digital subtraction
      angiography (DSA). 81 children aged 1-18 (median 10) years were studied with 62%
      (51) having a diagnosis of RVD. Main renal artery disease, intrarenal disease,
      and both main and intrarenal artery disease were present in 25, 14, and 12
      patients respectively. The isotope study accurately diagnosed RVD, confirmed by
      DSA, in 47% (24 of 51) children, with eight false positive studies. The
      sensitivity, specificity, and positive and negative predictive values of the
      isotope study to predict RVD were 48%, 73%, 76%, and 51%, respectively. Pre- and
      postcaptopril renal scintigraphy was unable to predict RVD in children.

PMID- 19756765
TI  - Comparison between fractional excretions of urea  and sodium in children with
      acute kidney injury.
AB  - Fractional excretion of sodium (FENa) has been said to be the most sensitive
      index for differentiating prerenal failure (PRF) from intrinsic renal failure
      (IRF). However, there are several instances of high FENa (>2%) in cases of PRF
      and low FENa (<1%) in IRF patients. In contrast, the fractional excretion of urea
      nitrogen (FEUN) is primarily dependent on passive forces, and many confounding
      variables that affect FENa have little effect on FEUN, if any. To compare FEUN
      with FENa, pediatric patients with acute kidney injury (AKI) were prospectively
      evaluated by history, physical examination, and obtaining appropriate laboratory
      data during a 1-year interval. Diagnosis of PRF or IRF was made in each patient,
      and renal failure indices were compared between two groups using chi-square and t
      test, as appropriate. Probability value (P value) <0.05 was considered
      significant. Receiver operating characteristic (ROC) plots for FEUN and FENa were
      drawn to compare the discriminative power of each index. Forty-three patients
      were enrolled in the study. There were 27 patients in the PRF and 16 in the IRF
      group. FENa was 2+/-0.4 in PRF and 4.5+/- 1% in IRF patients (P<0.05), and low
      FENa (<1%) was only seen in 44.4% of PRF patients, which was not statistically
      different from those with IRF (P>0.05). FEUN was 23.6+/- 4.9% in PRF and 41.6+/
      4.8% in IRF patients (P<0.05), and low FEUN (<35%) was seen in 77.8% of the PRF
      group (P<0.05). Cutoff values of 30% and 1.6% were reached for FEUN and FENa,
      respectively. In conclusion, FEUN <35% had higher sensitivity and specificity
      than FENa <1% for differentiation of PRF from IRF.

PMID- 19756766
TI  - [How many patient deaths can a team cope with? : a nationwide survey of
      palliative care units in Germany].
AB  - BACKGROUND: How many patient deaths the teams at palliative care units can cope
      with, the supporting factors in coping and the future prospects of the teams have
      not yet been subject to research in Germany. The aim of the study was to assess
      burden factors, burden symptoms and protective factors, the critical number and
      distribution of patient deaths as well as the prospects of the teams. SAMPLE AND
      METHODS: A total of 873 members of palliative care teams from 95 (60% of n=158)
      German palliative care units took part in this explorative evaluation. Basic
      factors could be identified using factor analysis. Differences between
      professional groups were checked with analysis of variance. RESULTS: Results
      showed that not having reached the objectives of palliative care was the central
      burden factor. In the majority of cases a team reacted by being loquacious. The
      team itself was ranked as the most important protective factor. The mean critical
      number of deaths was 4.4 per week. Consecutive patient deaths were rated as being
      significantly more stressful than evenly spread deaths. Ratings for the future
      prospects of the team were significantly lower in teams where not meeting the
      objectives of palliative care was considered a high burden factor. CONCLUSION: A
      clearer definition of the objectives of palliative care and support of team
      communication are desirable.

PMID- 19756767
TI  - [Neuromodulation of spasticity in children by intrathecal baclofen].
AB  - INTRODUCTION: Treatment with intrathecal baclofen (ITB) is an important part of
      the complex therapy of patients with cerebral spasticity aiming to improve the
      motoric functions and to reduce pain intensity. MATERIAL AND METHODS: ITB was
      started in the Orthopaedic Hospital in Speising in 1999. From 1999 to 2006 a
      total of 15 children aged 3 to 16 years old were selected for this special
      treatment. RESULTS: The average degree of spasticity according to Ashworth (scale
      1-5) could be reduced by ITB from 4.38 to 3.0, the time spent sitting could be
      increased from 3.3 to 5.8h per day and the pain intensity (VAS 1-10) could be
      reduced from 4.2 to 0.6. The time necessary for nursing treatment was shortened
      from 7.5 to 3.4 (VAS 1-10). Also improved was the emotional situation, the
      ability to swallow, the posture of the head and the concentration ability.
      CONCLUSION: ITB provides neuromodulation even in pediatric patients with complex
      neuromotoric spasticity.

PMID- 19756768
TI  - [Obligatory documentation for narcotic drugs over the course of time : the
      morphine and cocaine book for physicians according to the 1930 parliamentary law
      gazette].
AB  - According to the opium law and prescription statute of 1930, physicians were duty
      bound to maintain a stock ledger to allow a traceable record of the location of
      narcotic drugs. If a simplification of the prescription of opiates was welcomed
      10 years ago then 2 years after amendment of the addictive drugs statute thought
      should be give to safe use, as can be concluded from a morphine logbook from the
      time of the introduction of the Federal opium law. "Receipt and issue...
      deliverer and recipient" must be able to be extracted from the documentation,
      which means the delivery and the dispensing but not the individual application.

PMID- 19756769
TI  - [Neuroablative procedures in pain therapy].
AB  - Although surgical ablative procedures can be effective in the management of
      chronic pain of malignant and non-malignant origin, they are often disregarded as
      treatment options due to the fact that in the past these procedures were
      associated with high complication rates. The complications include the
      development of new neurological deficits and in cases of long-term follow-up, the
      occurrence of the old or new pain syndromes by deafferentation. On the other hand
      there exist many less invasive, e.g. neuromodulatory procedures or non-invasive
      measures (systemic oral or transdermal opioids) which are able to considerably
      reduce chronic pain. Nevertheless, there remain certain very restricted
      indications for the use of neuroablative procedures for the treatment of chronic
      pain even today.

PMID- 19756770
TI  - [Evaluation of a multimodal pain therapy at the University Pain Centre Dresden].
AB  - BACKGROUND: Data of a multimodal pain management program of the multidisciplinary
      pain management centre at the University Hospital of Dresden is presented. Over a
      period of 4 weeks, supplemented by an additional week 3 months later (booster
      week), patients with chronic pain of different origins are being treated in
      groups of 12. Based on the principles of the biopsychosocial pain model and the
      idea of functional restoration, the program is dedicated for pain patients where
      outpatient treatment was insufficient. METHODS: The program was evaluated on the
      basis of pain intensity (NRS), pain disability (PDI), fear and depression (HADS
      D), catastrophizing (CSQ) and health-related quality of life and vitality (SF
      36). The data were collected at the beginning and end of the initial 4 week
      treatment period, at the end of the booster period as well as 6 and 12 months
      after the end of active treatment. RESULTS: A total of 189 patients were included
      in the program in the period from January 2006 until August 2008. All outcome
      parameter showed statistically significant improvements with small to high effect
      sizes (ES 0.20-0.95). The results stayed stable even 1 year after the treatment.
      The highest effect sizes were found in catastrophizing (ES 0.86) and average pain
      intensity (ES 0.95). The primary pain diagnosis (e. g. low back pain versus
      headache) had no impact on treatment outcome. CONCLUSION: Significant and
      clinically relevant improvements could be achieved with the multimodal pain
      management program in groups of 12 patients. The results were stable over a time
      period of 1 year. Pain diagnosis had no impact on the outcome.

PMID- 19756771
TI  - Modelling radiation fluxes in simple and complex environments: basics of the
      RayMan model.
AB  - Short- and long-wave radiation flux densities absorbed by people have a
      significant influence on their energy balance. The heat effect of the absorbed
      radiation flux densities is parameterised by the mean radiant temperature. This
      paper presents the physical basis of the RayMan model, which simulates the short-
      and long-wave radiation flux densities from the three-dimensional surroundings in
      simple and complex environments. RayMan has the character of a freely available
      radiation and human-bioclimate model. The aim of the RayMan model is to calculate
      radiation flux densities, sunshine duration, shadow spaces and thermo
      physiologically relevant assessment indices using only a limited number of
      meteorological and other input data. A comparison between measured and simulated
      values for global radiation and mean radiant temperature shows that the simulated
      data closely resemble measured data.

PMID- 19756772
TI  - Heated (37 degrees C) oxaliplatin infusion in combination with capecitabine for
      metastatic colorectal carcinoma: can it reduce neuropathy?
AB  - BACKGROUND/PURPOSE: Oxaliplatin-associated neuropathy remains a dose-limiting
      toxicity of the standard chemotherapy regimen of oxaliplatin and capecitabine for
      metastatic colorectal cancer. No preventive strategy has definitively been
      established. Because this neuropathy is triggered by cold, we hypothesized that
      infusing oxaliplatin at 37 degrees C might reduce neuropathy. METHODS: In this
      open-label pilot feasibility trial, patients with no prior chemotherapy for
      metastatic colorectal cancer were included. Treatment consisted of capecitabine
      1,000 mg/m(2) bid on days 1-14 and oxaliplatin 130 mg/m2 on day 1 of a 21-day
      cycle. The oxaliplatin infusion was administered through a fluid-warming device
      at a constant temperature of 37 degrees C over 2 h. The primary endpoint was
      feasibility and drug reactions during the infusion. Secondary endpoints included
      acute and chronic neuropathy as well as response rate. RESULTS: Twenty patients
      were enrolled, and a total of 95 cycles administered. Median cumulative
      oxaliplatin dose was 735 mg/m(2). Apart from one patient with laryngeal spasm, no
      other infusion-related adverse events were observed. Of the patients, 35%
      reported grade 3/4 acute dysesthesia or paresthesia according to a patients
      questionnaire. Chronic neuropathy according to NCI CTC v3.0 was observed in 85%
      (grade 1) and 15% (grade 2), respectively. The overall response rate was 45% (95%
      CI 23-67%; 5% complete remission; 40% partial remission) and stable disease was
      achieved in another 30% of patients. CONCLUSION: Administration of heated
      oxaliplatin in combination with capecitabine is feasible and well tolerated
      without additional toxicity. While we have observed a relatively low rate of
      chronic cumulative neuropathy with heated oxaliplatin, this procedure appears not
      promising enough for us to recommend its further clinical evaluation.

PMID- 19756773
TI  - Treatment of cancer-related anorexia with olanzapine and megestrol acetate: a
      randomized trial.
AB  - PURPOSE: The purpose of the study was to determine the effectiveness of megestrol
      acetate (MA) and olanzapine (OLN) for the treatment of cancer-related anorexia
      (CRA). METHODS: Eighty adult patients with advanced gastrointestinal cancer or
      lung cancer (stages III and IV) with CRA (loss of appetite and greater than or
      equal to 5% loss of preillness stable weight) were randomized to receive daily MA
      or MA plus OLN for a period of 8 weeks. Patients were assessed weekly using the
      M.D. Anderson Symptom Inventory with specific measurement of weight, appetite,
      nausea, and quality of life (QOL) measures. RESULTS: For the 37 patients
      receiving MA, 15 patients had a greater than or equal to 5% weight gain, 2
      patients had an appetite improvement, 3 patients had an improvement in nausea,
      and 5 patients had an improvement in QOL at both 4 and 8 weeks. For the 39
      patients receiving MA plus OLN, 33 patients had a greater than or equal to 5%
      weight gain, 25 patients had an appetite improvement, 21 patients had an
      improvement in nausea, and 23 patients had an improvement in QOL at both 4 and 8
      weeks, and there was an improvement in general activity, mood, work, walking, and
      enjoyment at 8 weeks. There were no grade III or IV treatment-related toxicities
      in patients receiving MA or the combination of MA plus OLN. CONCLUSIONS: The
      combination of MA and OLN appears to be an effective intervention for patients
      with CRA.

PMID- 19756774
TI  - Evaluation of risk factors predictive of nausea and vomiting with current
      standard-of-care antiemetic treatment: analysis of two phase III trials of
      aprepitant in patients receiving cisplatin-based chemotherapy.
AB  - GOALS OF WORK: Certain patient and treatment characteristics are predictive of
      chemotherapy-induced nausea and vomiting (CINV). Objectives of this analysis
      were: (1) confirm the importance of several previously reported adverse risk
      factors for CINV in patients receiving chemotherapy, (2) assess the impact of the
      NK(1) receptor antagonist aprepitant according to these risk factors, and (3)
      assess the impact of age on antiemetic outcome. PATIENTS AND METHODS: Patients
      from two double-blind, placebo-controlled trials were randomized to an active
      control group (ondansetron 32 mg IV, dexamethasone 20 mg PO day 1; dexamethasone
      8 mg bid days 2-4) or an aprepitant group (aprepitant 125 mg PO, ondansetron 32
      mg IV, dexamethasone 12 mg day 1; aprepitant 80 mg days 2-3; dexamethasone 8 mg
      qd days 2-4). The primary endpoint was complete response (no emesis or rescue
      therapy use). In a post-hoc analysis, multivariate logistic regression models
      were used to assess the impact of treatment with aprepitant and previously
      reported risk factors, using a modified intent-to-treat approach. MAIN RESULTS:
      Treatment with aprepitant (p < 0.0001), male gender (p = 0.023), cisplatin dose
      <80 mg/m(2) (p = 0.001), age >or=65 years (p = 0.021), and five or more alcoholic
      drinks per week (p = 0.027) were all significantly associated with improved
      complete response. Aprepitant improved complete response regardless of risk for
      all factors and neutralized the risk associated with female gender. CONCLUSIONS:
      This analysis confirmed the relevance of several previously reported risk factors
      for CINV in patients receiving chemotherapy. Aprepitant improved complete
      response regardless of risk and eliminated the increased risk of CINV associated
      with the female gender.

PMID- 19756775
TI  - An onco-informatics database for anticancer drug interactions with complementary
      and alternative medicines used in cancer treatment and supportive care: an
      overview of the OncoRx project.
AB  - PURPOSE: Cancer patients are at high risk of manifesting interactions from use of
      anticancer drugs (ACDs) and complementary and alternative medicines (CAMs). These
      interactions can result in sub-therapeutic effects or increased toxicities which
      may compromise the outcome of chemotherapy. It is important for practitioners to
      gain convenient access to ACD-CAM interaction information so as to make better
      informed decisions in daily practice. This paper describes the creation of an
      oncology database (OncoRx) that documents ACD-CAM interactions, including
      traditional Chinese medicines (TCMs) that are commonly used for cancer treatment,
      prevention, and supportive care therapy. METHODS: Information regarding ACDs,
      CAMs, and drug interactions were collated from 14 sources, inclusive of hardcopy
      and online resources, and input into a modified web server with a database engine
      and a programming interface using a combination of software and programming
      scripts. RESULTS: OncoRx currently contains a total of 117 ACDs and 166 CAMs.
      Users are able to search for interactions based on various CAM uses: cancer
      treatment or prevention, immune-system-related, alopecia, nausea, and vomiting,
      peripheral neuropathy and pain, inflammation, fatigue, and non-cancer related.
      Pharmacokinetic data on ACDs and CAMs, characteristics of CAMs based on TCM
      principles, and drug interaction parameters such as effects, mechanisms,
      evidences, and proposed management plans, are shown in the search results.
      CONCLUSION: OncoRx is an oncology database which detects ACD interactions. It is
      currently able to detect interactions with CAMs. It is hoped that OncoRx will
      serve as a useful resource to clinicians, educators, trainers, and students
      working in the oncology setting.

PMID- 19756776
TI  - Ectomycorrhizal fungal communities of pedunculate and sessile oak seedlings from
      bare-root forest nurseries.
AB  - In this study, we present the detailed molecular investigation of the
      ectomycorrhizal (ECM) community of Quercus petraea and Quercus robur seedlings
      grown in bare-root forest nurseries. In all tested oak samples, mycorrhizal
      colonization was nearly 100%. Morphological observation and molecular
      investigations (sequencing of fungal ITS rDNA) revealed a total of 23 mycorrhizal
      taxa. The most frequent and abundant fungal taxa were Hebeloma sacchariolens,
      Tuber sp., and Peziza sp.; from the detected fungal taxa, 20 were noted for Q.
      petraea and 23 for Q. robur. Depending on the nursery, the species richness of
      identified ECM fungal taxa for both oak species ranged from six to 11 taxa. The
      mean species richness for all nurseries was 5.36 and 5.82 taxa per Q. petraea and
      Q. robur sample, respectively. According to the analysis of similarity, ECM
      fungal communities were similar for Q. petraea and Q. robur (R = 0.019; p =
      0.151). On the other hand, detected fungal communities were significantly
      different between nurseries (R = 0.927; p < 0.0001). Using the Spearman rank
      correlation, it was determined that the ectomycorrhizal diversity (in terms of
      richness, the Shannon diversity, evenness, and Simpson dominance indices) is
      significantly related to the soil parameters of each nursery. We conclude that
      individual nursery may be considered as separate ecological niches that strongly
      discriminate diversity of ECM fungi.

PMID- 19756777
TI  - Ectomycorrhizal species associated with Pinus radiata in New Zealand including
      novel associations determined by molecular analysis.
AB  - Ectomycorrhizal (ECM) associates of the exotic plantation species Pinus radiata
      were investigated above and below ground over two years in the North Island of
      New Zealand. ECM species were identified using morphological and molecular
      (restriction fragment length polymorphism and DNA sequencing) analysis. Eighteen
      ECM species were observed fruiting above ground; 19 ECM species were identified
      below ground. In the above ground study, Wilcoxina mikolae, Rhizopogon
      pseudoroseolus and Inocybe sindonia were noted for the first time as ECM
      associates of P. radiata in New Zealand. Below ground, the species W. mikolae, R.
      pseudoroseolus, Rhizopogon luteorubescens, Pseudotomentella sp., Pseudotomentella
      tristis and Tomentella sp. were found as new associates of P. radiata in New
      Zealand. Additionally, six ECM types were found that could not be identified with
      molecular analysis. The putative ECM taxa Tricholoma pessundatum, Laccaria
      laccata and Hebeloma crustuliniforme were examined by molecular analysis, and
      species identifications were proposed to be changed to Tricholoma sp., L. laccata
      and Hebeloma sp. for specimens associated with P. radiata in New Zealand. The
      species identity of I. sindonia, previously unidentified to species level, was
      determined with direct sequencing.

PMID- 19756778
TI  - Response of mycorrhizal periwinkle plants to aster yellows phytoplasma infection.
AB  - The objective of our research was to assess if arbuscular mycorrhizal (AM) fungal
      colonization can modify the effect of infection by two aster yellows phytoplasma
      strains (AY1, AYSim) in Catharanthus roseus plants. Both phytoplasma strains had
      a negative effect on the root fresh weight, but they differed in symptoms
      appearance and in their influence on photosynthetic and transpiration rates of
      the periwinkle plants. AM plants showed significantly reduced shoot fresh weight,
      while the transpiration rate was significantly increased. AM fungal colonization
      significantly affected shoot height and fresh weight of the plants infected by
      each phytoplasma strains as well as the root system of plants infected with the
      more aggressive AYSim phytoplasma strain. Double inoculation did not reduce the
      negative effects induced with phytoplasma alone on the photosynthetic activity of
      phytoplasma-infected plants.

PMID- 19756779
TI  - Arbuscular mycorrhiza partially protect chicory roots against oxidative stress
      induced by two fungicides, fenpropimorph and fenhexamid.
AB  - The present work examined the oxidative stress induced by different
      concentrations (0.02 and 0.2 mg l-1) of two sterol biosynthesis inhibitor
      fungicides (fenpropimorph and fenhexamid) in non-target chicory root colonised or
      not by Glomus intraradices in a monoxenic system. The fungicides were found to
      cause oxidative damage by increasing lipid peroxidation measured by
      malondialdehyde production in non-colonised roots. Detoxification of the H(2)O(2)
      product was measured at 0.2 mg l-1 of fenpropimorph by an increase in peroxidase
      activities suggesting an antioxidant capacity in these roots. Moreover, this
      study pointed out the ability of arbuscular mycorrhiza to alleviate partially the
      oxidative stress in chicory roots, probably by lowering reactive oxygen species
      concentrations, resulting from increases in antioxidant defences. Our results
      suggest that the enhanced fungicide tolerance in the AM symbiosis could be
      related to less cell membrane damage.

PMID- 19756780
TI  - Vertebroplasty: about sense and nonsense of uncontrolled "controlled randomized
      prospective trials".

PMID- 19756781
TI  - Transforaminal endoscopic surgery for symptomatic lumbar disc herniations: a
      systematic review of the literature.
AB  - The study design includes a systematic literature review. The objective of the
      study was to evaluate the effectiveness of transforaminal endoscopic surgery and
      to compare this with open microdiscectomy in patients with symptomatic lumbar
      disc herniations. Transforaminal endoscopic techniques for patients with
      symptomatic lumbar disc herniations have become increasingly popular. The
      literature has not yet been systematically reviewed. A comprehensive systematic
      literature search of the MEDLINE and EMBASE databases was performed up to May
      2008. Two reviewers independently checked all retrieved titles and abstracts and
      relevant full text articles for inclusion criteria. Included articles were
      assessed for quality and outcomes were extracted by the two reviewers
      independently. One randomized controlled trial, 7 non-randomized controlled
      trials and 31 observational studies were identified. Studies were heterogeneous
      regarding patient selection, indications, operation techniques, follow-up period
      and outcome measures and the methodological quality of these studies was poor.
      The eight trials did not find any statistically significant differences in leg
      pain reduction between the transforaminal endoscopic surgery group (89%) and the
      open microdiscectomy group (87%); overall improvement (84 vs. 78%), re-operation
      rate (6.8 vs. 4.7%) and complication rate (1.5 vs. 1%), respectively. In
      conclusion, current evidence on the effectiveness of transforaminal endoscopic
      surgery is poor and does not provide valid information to either support or
      refute using this type of surgery in patients with symptomatic lumbar disc
      herniations. High-quality randomized controlled trials with sufficiently large
      sample sizes are directly needed to evaluate if transforaminal endoscopic surgery
      is more effective than open microdiscectomy.

PMID- 19756782
TI  - Factors accounting for psychosocial functioning in patients with low back pain.
AB  - Low back pain (LBP) is a chronic disorder which exerts a profound impact on
      various spheres of psychosocial functioning, including emotional distress,
      functional limitations and decrements in social contacts. The objective of this
      study was to investigate the associations between the indices of psychosocial
      functioning in patients with chronic LBP and a range of psychological factors.
      Specifically, the study aimed at exploring the relative participation of
      personality, social support, disease-related cognitive appraisals and coping
      styles in accounting for the differences in psychosocial functioning of patients
      with LBP. One-hundred-twenty patients with LBP took part in the study and
      completed a battery of psychological questionnaires: NEO-Five Factors Inventory,
      Ways of Coping Questionnaire, Disease-Related Social Support Scale, Disease
      Related Appraisals Scale and Psychosocial Functioning Questionnaire (PFQ). The
      PFQ dimensions were used as dependent variables in a series of stepwise
      regression analysis models with the scores from other questionnaires entered as
      independent variables. A cognitive appraisal of the disease in terms of an
      obstacle was strongly related to all domains of functioning; however, other
      appraisals (threat, challenge, harm, profit and overall disease importance) were
      uniquely associated with particular domains of functioning. Deprivation of social
      support was a significant predictor of distress experienced in interpersonal
      context and of sense of being disabled. Among basic personality traits,
      agreeableness was negatively associated with distress in interpersonal context,
      and conscientiousness was positively related to acceptance of life with the
      disease. Problem-focus coping was linked to higher acceptance of life with the
      disease. Among sociodemographic variables, older age and lower educational level
      were related to greater subjective feelings of being disabled. Pain severity was
      found unrelated to any of psychosocial functioning domains. Different aspects of
      psychosocial functioning are best accounted for by diverse patterns of
      psychological factors, which suggests involvement of different psychological
      mechanisms in development of LBP-related disability.

PMID- 19756783
TI  - Aminequinone-hydroxylquinoneimine tautomeric equilibrium revisited: molecular
      modeling study of the tautomeric equilibrium and substituent effects in 4-(4-R
      phenylamino)naphthalene-1,2-diones.
AB  - Semi-empirical (AM1 and PM3) and DFT (B3LYP/6-31G(d)) calculations were employed
      to study the tautomeric equilibrium between the aminequinone A and
      hydroxylquinoneimine B forms of 4-(4-R-phenylamino)naphthalene-1,2-diones.
      Substituent effects on the tautomeric equilibrium as well as on geometric and
      electronic parameters were also determined. In the gas phase the
      hydroxylquinoneimine B form is the most stable, whereas in water the aminequinone
      A form becomes more stable. The substituents do not modify the relative energies
      of the two tautomers. These results are in accordance with experimental data
      reported in the literature.

PMID- 19756784
TI  - High stability of a new Granada medium agar that allows rapid and accurate
      detection of colonization with group B streptococci in pregnant women.

PMID- 19756785
TI  - Clonal spread of CC17 vancomycin-resistant Enterococcus faecium with multilocus
      sequence type 78 (ST78) and a novel ST444 in Taiwan.
AB  - From May 2007 to January 2008, 30 isolates of vancomycin-resistant enterococci
      (VRE), including 29 Enterococcus faecium (96.7%) and 1 E. faecalis (3.3%) were
      obtained from various clinical specimens of 30 patients treated at a university
      hospital in Taiwan. Among these patients, 27 had VRE infections, including
      urinary tract infection (n = 16), bacteremia (n = 5), wound infection (n = 5),
      and central nervous system infection (n = 1). Three patients had VRE
      colonization. All of these isolates belonged to the vanA genotype with vancomycin
      minimum inhibitory concentrations of 64>or=128 microg/ml. The isolate of E.
      faecalis had VanB phenotype-vanA genotype. All these isolates were susceptible to
      linezolid and were inhibited by tigecycline at 0.25 microg/ml. Multilocus
      sequence typing (MLST) analysis of the E. faecium isolates showed that 82.8% were
      ST78, which belongs to lineage C1. Transposon typing classified the 30 isolates
      of VRE into three types and most of the Tn1546-like elements contained an IS1251
      like insertion sequence. Mating experiments showed that the vanA gene clusters
      were transferable at a frequency of about 10(-6) to 10(-7). Our findings indicate
      that nosocomial spread of VRE resulted from dissemination of lineage C1 E.
      faecium clones, including a novel E. faecium MLST type (ST444), and the
      horizontal transfer of Tn1546 elements among enterococci.

PMID- 19756786
TI  - Performance of Oxoid Brilliance MRSA medium for detection of methicillin
      resistant Staphylococcus aureus: an in vitro study.
AB  - Oxoid Brilliance MRSA was evaluated for its ability to identify methicillin
      resistant Staphylococcus aureus. A well-defined collection of staphylococci was
      used (n = 788). After 20 h incubation, the sensitivity was 99.6% and the
      specificity was 97.3%. This new medium is a highly sensitive method of screening
      for MRSA.

PMID- 19756788
TI  - Sex-dependent gene regulatory networks of the heart rhythm.
AB  - Expression level, control, and intercoordination of 66 selected heart rhythm
      determinant (HRD) genes were compared in atria and ventricles of four male and
      four female adult mice. We found that genes encoding various adrenergic
      receptors, ankyrins, ion channels and transporters, connexins, cadherins,
      plakophilins, and other components of the intercalated discs form a complex
      network that is chamber dependent and differs between the two sexes. In addition,
      most HRD genes in atria had higher expression in males than in females, while in
      ventricles, expression levels were mostly higher in females than in males.
      Moreover, significant chamber differences were observed between the sexes, with
      higher expression in atria than ventricles for males and higher expression in
      ventricles than atria for females. We have ranked the selected genes according to
      their prominence (new concept) within the HRD gene web defined as extent of
      expression coordination with the other web genes and stability of expression.
      Interestingly, the prominence hierarchy was substantially different between the
      two sexes. Taken together, these findings indicate that the organizational
      principles of the heart rhythm transcriptome are sex dependent, with the newly
      introduced prominence analysis allowing identification of genes that are pivotal
      for the sexual dichotomy.

PMID- 19756789
TI  - Non-climacteric fruit ripening in pepper: increased transcription of EIL-like
      genes normally regulated by ethylene.
AB  - Only limited information has been published to date on the similarities and
      differences between climacteric and non-climacteric fruit ripening on
      transcriptional level. To address this issue, we performed a direct comparative
      transcriptome analysis between tomato and pepper fruits using heterologous
      microarray hybridization. Given the significant differences in the morphological,
      physiological, and biochemical characteristics of pepper and tomato fruits, the
      existence of extensive common regulons is surprising. This finding suggests the
      conservation of ripening mechanisms in climacteric and non-climacteric fruits.
      However, disparate expression profiles were also observed in both fruits. This
      study revealed that a gene that encodes an enzyme that converts lycopene to
      downstream carotenoids is induced in pepper but not in tomato. Most of the genes
      that encode ribosomal proteins are only induced in early fruit-stage pepper fruit
      and show rapidly diminishing expression in the later developmental stages. The
      genes involved in ethylene biosynthesis were not induced in pepper fruit.
      However, the EIL-like genes, ethylene-mediated signaling components, were induced
      in pepper fruit. Divergent types of transcription factors were expressed in
      ripening tomato and pepper fruits, suggesting they may be key factors that
      differentiate these distinct ripening processes.

PMID- 19756791
TI  - Commentary on "Adhesion and membrane tension of single vesicles and living cells
      using a micropipette-based technique" by M.-J. Colbert et al.

PMID- 19756790
TI  - Neuropeptide signaling near and far: how localized and timed is the action of
      neuropeptides in brain circuits?
AB  - Neuropeptide signaling is functionally very diverse and one and the same
      neuropeptide may act as a circulating neurohormone, as a locally released
      neuromodulator or even as a cotransmitter of classical fast-acting
      neurotransmitters. Thus, neuropeptides are produced by a huge variety of neuron
      types in different parts of the nervous system. Within the central nervous system
      (CNS) there are numerous types of peptidergic interneurons, some with strictly
      localized and patterned branching morphologies, others with widespread and
      diffuse arborizations. From morphology alone it is often difficult to predict the
      sphere of influence of a peptidergic interneuron, especially since it has been
      shown that neuropeptides can diffuse over tens of micrometers within neuropils,
      and that peptides probably are released exclusively in perisynaptic (or non
      synaptic) regions. This review addresses some questions related to peptidergic
      signaling in the insect CNS. How diverse are the spatial relations between
      peptidergic neurons and their target neurons and what determines the sphere of
      functional influence? At one extreme there is volume transmission and at the
      other targeted cotransmission at synapses. Also temporal aspects of peptidergic
      signaling are of interest: how transient are peptidergic messages? Factors
      important for these spatial and temporal aspects of peptidergic signaling are
      proximity between release sites and cognate receptors, distribution of peptidase
      activity that can terminate peptide action and colocalization of other
      neuroactive compounds in the presynaptic peptidergic neuron (and corresponding
      receptors in target neurons). Other factors such as expression of different
      channel types, receptor inactivation mechanisms and second messenger systems
      probably also contribute to the diversity in temporal properties of peptide
      signaling.

PMID- 19756792
TI  - Continuum theory of lipid bilayer electrostatics.
AB  - In order to address the concerns about the applicability of the continuum theory
      of lipid bilayers, we generalize it by including a film with uniaxial dielectric
      properties representing the polar head groups of the lipid molecules. As a
      function of the in-plane dielectric constant kappa|| of this film, we encounter a
      sequence of different phases. For low values of kappa||, transmembrane pores have
      aqueous cores, ions are repelled by the bilayer, and the ion permeability of the
      bilayer is independent of the ion radius as in the existing theory. For
      increasing kappa||, a threshold is reached--of the order of the dielectric
      constant of water--beyond which ions are attracted to the lipid bilayer by
      generic polarization attraction, transmembrane pores collapse, and the ion
      permeability becomes sensitively dependent on the ion radius, results that are
      more consistent with experimental and numerical studies of the interaction of
      ions with neutral lipid bilayers. At even higher values of kappa||, the ion/pore
      complexes are predicted to condense in the form of extended arrays. The
      generalized continuum theory can be tested quantitatively by studies of the ion
      permeability as a function of salt concentration and co-surfactant concentration.

PMID- 19756793
TI  - Defect structures in nematic liquid crystals around charged particles.
AB  - We numerically study the orientation deformations in nematic liquid crystals
      around charged particles. We set up a Ginzburg-Landau theory with inhomogeneous
      electric field. If the dielectric anisotropy epsilon 1 is positive, Saturn-ring
      defects are formed around the particles. For epsilon 1< 0 , novel "ansa" defects
      appear, which are disclination lines with their ends on the particle surface. We
      find unique defect structures around two charged particles. To lower the free
      energy, oppositely charged particle pairs tend to be aligned in the parallel
      direction for epsilon 1> 0 and in the perpendicular plane for epsilon 1< 0 with
      respect to the background director. For identically charged pairs the preferred
      directions for epsilon 1> 0 and epsilon 1< 0 are exchanged. We also examine
      competition between the charge-induced anchoring and the short-range anchoring.
      If the short-range anchoring is sufficiently strong, it can be effective in the
      vicinity of the surface, while the director orientation is governed by the long
      range electrostatic interaction far from the surface.

PMID- 19756794
TI  - Recirculation model for liquid flow in foam channels.
AB  - Although extensively studied in the past, drainage of aqueous foams still offers
      major unaddressed issues. Among them, the behaviour of foam films during drainage
      has great significance as the thickness of the films is known to control the
      Ostwald ripening in foams, which in turn impacts liquid drainage. We propose a
      model relating the films' behavior to the liquid flow in foam channels. It is
      assumed that Marangoni-driven recirculation counterflows take place in the
      transitional region between the foam channel and the adjoining films, and the
      Gibbs elasticity is therefore introduced as a relevant parameter. The velocity of
      these counterflows is found to be proportional to the liquid velocity in the
      channel. The resulting channel permeability is determined and it is shown that
      Marangoni stresses do not contribute to rigidify the channel's surfaces, in
      strong contrast with the drainage of horizontal thin liquid films. New
      experimental data are provided and support the proposed model.

PMID- 19756795
TI  - Elasticity of polymer solutions in Couette flow measured by fluorescence
      resonance energy transfer (FRET).
AB  - Polymer solutions are complex fluids that show elasticity and deformation in
      response to shear flows. A fluorescence resonance energy transfer (FRET)
      technique has been applied to measure the end-to-end distances of individual
      polymer molecules in Couette flow, using end-tagged reversible-addition
      fragmentation chain transfer (RAFT) polymerised poly(methyl methacrylate) (PMMA).
      Real-time rheofluorescence measurements on these polymers in solution above the
      critical overlap concentration are reported at several shear rates. The PMMA in
      Couette flow shows a systematic decrease in fluorescence, corresponding to a
      reduction in end-to-end distance of the polymer molecules with shear exposure.
      Full reversibility of the fluorescence signal is observed after the cessation of
      shear. These results show that polymer solution elasticity arises from
      compressive deformation of the polymer molecules in Couette flow. At polymer
      concentrations above the critical overlap, the polymer molecules are restricted
      by their neighbours and the net hydrodynamic forces are compressive rather than
      extensive.

PMID- 19756796
TI  - Health insurance for the poor: impact on catastrophic and out-of-pocket health
      expenditures in Mexico.
AB  - The goal of Seguro Popular (SP) in Mexico was to improve the financial protection
      of the uninsured population against excessive health expenditures. This paper
      estimates the impact of SP on catastrophic health expenditures (CHE), as well as
      out-of-pocket (OOP) health expenditures, from two different sources. First, we
      use the SP Impact Evaluation Survey (2005-2006), and compare the instrumental
      variables (IV) results with the experimental benchmark. Then, we use the same IV
      methods with the National Health and Nutrition Survey (ENSANUT 2006). We estimate
      naive models, assuming exogeneity, and contrast them with IV models that take
      advantage of the specific SP implementation mechanisms for identification. The IV
      models estimated included two-stage least squares (2SLS), bivariate probit, and
      two-stage residual inclusion (2SRI) models. Instrumental variables estimates
      resulted in comparable estimates against the "gold standard." Instrumental
      variables estimates indicate a reduction of 54% in catastrophic expenditures at
      the national level. SP beneficiaries also had lower expenditures on outpatient
      and medicine expenditures. The selection-corrected protective effect is found not
      only in the limited experimental dataset, but also at the national level.

PMID- 19756797
TI  - Copayments for ambulatory care in Germany: a natural experiment using a
      difference-in-difference approach.
AB  - In response to increasing health expenditures and a high number of physician
      visits, the German government introduced a copayment for ambulatory care in 2004
      for individuals with statutory health insurance (SHI). Because persons with
      private insurance were exempt from the copayments, this health-care reform can be
      regarded as a natural experiment. We used a difference-in-difference approach to
      examine whether the new copayment effectively reduced the overall demand for
      physician visits and to explore whether it acted as a deterrent to vulnerable
      groups, such as those with low income or chronic conditions. We found that there
      was no significant reduction in the number of physician visits among SHI members
      compared to our control group. At the same time, we did not observe a deterrent
      effect among vulnerable individuals. Thus, the copayment has failed to reduce the
      demand for physician visits. It is likely that this result is due to the design
      of the copayment scheme, as the copayment is low and is paid only for the first
      physician visit per quarter.

PMID- 19756798
TI  - An efficient two-stage approach for image-based FSI analysis of atherosclerotic
      arteries.
AB  - Patient-specific biomechanical modeling of atherosclerotic arteries has the
      potential to aid clinicians in characterizing lesions and determining optimal
      treatment plans. To attain high levels of accuracy, recent models use medical
      imaging data to determine plaque component boundaries in three dimensions, and
      fluid-structure interaction is used to capture mechanical loading of the diseased
      vessel. As the plaque components and vessel wall are often highly complex in
      shape, constructing a suitable structured computational mesh is very challenging
      and can require a great deal of time. Models based on unstructured computational
      meshes require relatively less time to construct and are capable of accurately
      representing plaque components in three dimensions. These models unfortunately
      require additional computational resources and computing time for accurate and
      meaningful results. A two-stage modeling strategy based on unstructured
      computational meshes is proposed to achieve a reasonable balance between meshing
      difficulty and computational resource and time demand. In this method, a coarse
      grained simulation of the full arterial domain is used to guide and constrain a
      fine-scale simulation of a smaller region of interest within the full domain.
      Results for a patient-specific carotid bifurcation model demonstrate that the two
      stage approach can afford a large savings in both time for mesh generation and
      time and resources needed for computation. The effects of solid and fluid domain
      truncation were explored, and were shown to minimally affect accuracy of the
      stress fields predicted with the two-stage approach.

PMID- 19756799
TI  - Enhanced FK506 production in Streptomyces clavuligerus CKD1119 by engineering the
      supply of methylmalonyl-CoA precursor.
AB  - FK506 is a 23-membered polyketide macrolide with immunosuppressant activity
      produced by Streptomyces species. The production of FK506 in S. clavuligerus
      CKD1119 (KCTC 10561BP) was improved by enhancing the supply of biosynthetic
      precursors. This improvement was approximately 2.5-fold (15 mg/l) with the
      supplementation of 10 mM methyl oleate, which is the probable source of acyl
      CoAs, to R2YE medium. When the level of FK506 production reached its maximum, the
      intracellular concentration of methylmalonyl-CoA in S. clavuligerus CKD1119
      supplemented with methyl oleate was 12.5-fold higher than that of the
      unsupplemented strain, suggesting that an increased methylmalonyl-CoA level
      caused the high-level production of FK506. The following three pathways for the
      production of (2S)-methylmalonyl-CoA were evaluated to identify the effective
      precursor supply pathway that can support the high production of FK506 in S.
      clavuligerus CKD1119: propionyl-CoA carboxylase, methylmalonyl-CoA mutase (MCM),
      and malonyl/methylmalonyl-CoA ligase. Of the three pathways examined, the MCM
      pathway supported the highest levels of FK506 production. The expression of MCM
      in S. clavuligerus CKD1119 led to a threefold and 1.5-fold increase in the
      methylmalonyl-CoA pool and FK506 production, respectively. Supplementing the
      culture broth of S. clavuligerus CKD1119 expressing MCM with methyl oleate
      resulted in an additional twofold increase in the FK506 titer (17.8 mg/l).
      Overall, these results show that the methylmalonyl-CoA supply is a limiting
      factor for FK506 biosynthesis and that among the three pathways analyzed, the MCM
      pathway is the most effective precursor supply pathway supporting the highest
      titer of FK506 in S. clavuligerus CKD1119.

PMID- 19756800
TI  - Strain development of Streptomyces sp. for tacrolimus production using sequential
      adaptation.
AB  - An immunosuppressant tacrolimus-producing strain of Streptomyces sp. TST8 was
      isolated and developed by the TS corporation in Korea using the sequential
      adaptation of media containing tacrolimus (600-1600 mg/l). The aim of the
      tacrolimus sequential adaptation protocol was to select those cells with
      tacrolimus resistance and to reduce product inhibition of the tacrolimus
      producing strain. The developed strains produced more tacrolimus than the
      original strain. In particular, the TST10 strain adapted in the medium containing
      900 mg/l of tacrolimus produced 972 mg/l of tacrolimus in the final titer after 7
      days of cultivation in a 5-l jar fermenter. This is the largest final titer of
      tacrolimus produced by a specific strain to date. Because the sequential
      adaptation protocol is limited by the solubility of tacrolimus in water, the
      final tacrolimus titer of TST11 adapted in the medium containing 1600 mg/l of
      tacrolimus was lower than that of TST10. The developed strains and the
      development method using sequential adaptation can facilitate the efficient and
      economical production of tacrolimus.

PMID- 19756801
TI  - Color Doppler imaging and pattern visual evoked potential in normal tension
      glaucoma and hypertension glaucoma.
AB  - To compare the differences in color Doppler imaging (CDI) and pattern visual
      evoked potential (P-VEP) examinations between normal tension glaucoma (NTG) and
      hypertension primary open angle glaucoma (HTG) patients, and investigate the
      relation between flow velocities measured by CDI and P-VEP examination in NTG and
      HTG patients. Sixty NTG patients, 66 HTG patients and 44 control subjects
      underwent CDI evaluation of the ophthalmic artery (OA), short posterior ciliary
      artery (SPCA) and central retinal arteries (CRA). The peak systolic velocities
      (PSV) and end-diastolic velocities (EDV) and resistive index (RI) of all
      retrobulbar vessels were measured. The latency and amplitude of P100 in P-VEP
      were recorded from the three groups. The differences of CDI and P-VEP parameters
      among NTG group, HTG group and control group were compared by one-way analysis of
      variance. The correlations between CDI parameters and visual field indices, P-VEP
      and visual field indices, P-VEP and CDI parameters in NTG and HTG patients were
      evaluated by Pearson's correlation analysis. NTG and HTG patients had the lower
      EDV and higher RI in the OA, CRA and SPCA comparing with that of control
      subjects. NTG and HTG patients also had lower PSV in OA and CRA comparing with
      that of control subjects. There was no significant difference in the blood flow
      velocities and RI of all retrobulbar vessels between NTG and HTG patients. The
      latency of P100 in VEP delayed and the amplitude of P100 decreased in the NTG and
      HTG patients comparing with that of the control group. There was no significant
      difference in the latency and amplitude of P100 between the NTG and HTG patients.
      The RI of OA and SPCA were negatively correlated with the mean deviation (MD)
      values in the NTG and HTG patients. The RI of OA was positively correlated with
      the PSD value in the NTG and HTG patients. The MD values in the NTG and HTG
      patients were negatively correlated with the latency time of P100. The RI of OA
      was positively correlated with the latency time of P100 in NTG and HTG patients.
      The RI of OA was negatively correlated with the amplitude of P100 in HTG
      patients. No significant difference was found in the parameters of CDI and P-VEP
      between NTG and HTG patients. The certain parameters of CDI were correlated with
      P-VEP parameters in NTG and HTG patients.

PMID- 19756803
TI  - Fixed-pressure nCPAP in patients with obstructive sleep apnea (OSA) syndrome and
      chronic obstructive pulmonary disease (COPD): a 24-month follow-up study.
AB  - PURPOSE: The aim of this study was to investigate the time course of body weight,
      daytime sleepiness, and functional cardiorespiratory parameters in patients with
      both chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea
      syndrome (OSA), after institution of domiciliary nasal continuous positive airway
      pressure (nCPAP). METHODS: Twelve consecutive obese outpatients (mean age = 61 +/
      11 years; four women) were evaluated before (baseline) and after 3, 12, and 24
      months of nocturnal nCPAP (4 h per night). RESULTS: At baseline, all patients
      were hypercapnic and hypoxemic, suffering from night desaturation (T (90) is the
      percentage of total recording time (TRT) spent with SaO(2) <or= 90% = 38 +/- 2%)
      and sleepy (Epworth sleepiness scale [ESS] = 16.58 +/- 0.86). Three months after
      the implementation of nCPAP, daytime PaCO(2) and PaO(2) improved up to 45.1 +/-
      0.9 and 69.0 +/- 1 mmHg, respectively; mean pulmonary artery pressure (MPAP)
      decreased from 24.7 +/- 1.1 to 19.2 +/- 04 mmHg. All other variables showed
      progressive improvements up to 12 months. At 3 and 12 months, mean body mass
      index was slightly decreased (to 31.6 +/- 0.2 and 30.7 +/- 0.1 kg/m(2),
      respectively); daytime sleepiness, nocturnal O(2) desaturation, and maximal
      inspiratory pressure were also improved and thereafter remained stable.
      CONCLUSIONS: In conclusion, in our patients with both severe OSA and mild-to
      moderate COPD, arterial blood gasses and MPAP improved and stabilized after 3
      months of nCPAP therapy, with the greatest improvements being in ESS score, T
      (90), and maximal inspiratory force from 3 up to 12 months; these parameters
      remained stable over the following 12 months. Finally, our data support early
      treatment with nCPAP in such patients.

PMID- 19756804
TI  - Degradation of hexane and other recalcitrant hydrocarbons by a novel isolate,
      Rhodococcus sp. EH831.
AB  - BACKGROUND, AIM, AND SCOPE: Hexane, a representative VOC, is used as a solvent
      for extraction and as an ingredient in gasoline. The degradation of hexane by
      bacteria is relatively slow due to its low solubility. Moreover, the
      biodegradation pathway of hexane under aerobic conditions remains to be
      investigated; therefore, a study relating to aerobic biodegradation mechanisms is
      required. Consequently, in this study, an effective hexane degrader was isolated
      and the biodegradation pathway examined for the first time. In addition, the
      degradation characteristics of a variety of recalcitrant hydrocarbons were
      qualitatively and quantitatively investigated using the isolate. MATERIALS AND
      METHODS: A hexane-degrading bacterium was isolated from an enrichment culture
      using petroleum-contaminated soil as an inoculum with hexane as the sole carbon
      and energy source. The bacterium was also identified using the partial 16S rRNA
      gene sequence. To test the hexane-degrading capacity of the isolate, 10 ml of an
      EH831 cell suspension was inoculated into a 600-ml serum bottle with hexane (7.6
      75.8 micromol) injected as the sole carbon source. The rates of hexane
      degradation were determined by analyzing the concentrations of hexane using
      headspace gas chromatography. In addition, the hexane biodegradation pathway
      under aerobic conditions was investigated by identifying the metabolites using
      gas chromatography-mass spectrometry with solid-phase microextraction. 14C-hexane
      was used to check if EH831 could mineralize hexane in the same experimental
      system. The degradabilities of other hydrocarbons were examined using EH831 with
      methanol, ethanol, acetone, cyclohexane, methyl tert-butyl ether (MTBE),
      dichloromethane (DCM), trichloroethylene, tetrachloroethylene, benzene, toluene,
      ethylbenzene, xylene (BTEX), pyrene, diesel, lubricant oil, and crude oil as sole
      carbon sources. RESULTS: A bacterium, EH831, was isolated from the enriched
      hexane-degrading consortium, which was able to degrade hexane and various
      hydrocarbons, including alcohols, chlorinated hydrocarbons, cyclic alkanes,
      ethers, ketones, monoaromatic and polyaromatic hydrocarbons, and petroleum
      hydrocarbons. The maximum hexane degradation rate (V max) of EH831 was 290
      micromol g dry cell weight(-1) h(-1), and the saturation constant (K s) was 15
      mM. Using 14C-hexane, EH831 was confirmed to mineralize approximately 49% of the
      hexane into CO2 and, converted approximately, 46% into biomass; the rest (1.7%)
      remained as extracellular metabolites in the liquid phase. The degradation
      pathway was assessed through the qualitative analysis of the hexane intermediates
      due to EH831, which were 2-hexanol, 2-hexanone, 5-hexen-2-one and 2,5
      hexanedione, in that order, followed by 4-methyl-2-pentanone, 3-methyl-1-butanol,
      3-methyl-1-butanone and butanal, and finally, CO2. EH831 could degrade methanol,
      ethanol, acetone, cyclohexane, MTBE, DCM, BTEX, pyrene, diesel, and lubricant
      oil. DISCUSSION: EH831 was able to degrade many recalcitrant hydrocarbons at
      higher degradation rates compared with previous well-known degraders.
      Furthermore, this study primarily suggested the aerobic biodegradation pathway,
      which may provide valuable information for researchers and engineers working in
      the field of environmental engineering. CONCLUSIONS: Rhodococcus sp. EH831 is a
      promising bioresource for removing hexane and other recalcitrant hydrocarbons
      from a variety of environments. Moreover, the aerobic biodegradation pathway is
      reported for the first time in this study, which offers valuable information for
      understanding the microbial degradation of hexane. RECOMMENDATIONS AND
      PERSPECTIVES: The utility of the strain isolated in this study needs to be proved
      by its application to biological process systems, such as biofilters and
      bioreactors, etc., for the degradation of hexane and many other recalcitrant
      hydrocarbons. Detailed investigations will also be needed to clarify the
      enzymatic characteristics relating the degradation of both recalcitrant
      hydrocarbons and hexane.

PMID- 19756805
TI  - Hybridization of the natural antibiotic, cinnamic acid, with layered double
      hydroxides (LDH) as green pesticide.
AB  - BACKGROUND, AIM, AND SCOPE: Heavy application of highly toxic synthetic
      pesticides has been committed to protect crops against insects and diseases,
      which have brought about serious environmental problems. Thus, an inevitable and
      fundamental issue has been how to protect crops without harmful effects on
      nature. As a fascinating nature-compatible approach, we have attempted to
      hybridize soil-compatible layered double hydroxides (LDHs) with natural
      antibiotic substances. Only a few of natural antibiotic substances are available
      for pest control mainly because of their inherent properties such as easy
      degradability, high minimum inhibition concentration for practical application,
      and often extremely low availability, whereas LDHs exhibit unique properties such
      as anion exchange capacity, acid lability, and high affinity to ubiquitous
      carbonate ion which make them an excellent inorganic matrix to carry labile
      biomolecules in soils. This study focuses on the behavior of cinnamate-LDH hybrid
      in soils and the evaluation of its potentials as a green pesticide. MATERIALS AND
      METHODS: The cinnamate-LDH hybrid was synthesized by a typical coprecipitation
      method. Cinnamic acid was analyzed by high performance liquid chromatography
      which was operated at 280 nm with C18 column. Its controlled release property was
      evaluated in a cultivated soil as well as a simulated soil solution. Its
      antifungal activity was examined against the growth of Phytophyhora capsici in a
      potato dextrose agar medium and a red pepper seedling, respectively. RESULTS AND
      DISCUSSION: Structural characterization by X-ray diffraction, infra-red, and
      thermal analysis indicates that cinnamate molecules are safely intercalated into
      the interlayer space of inorganic layers of LDH by the electrostatic interaction
      to have an empirical formula of Mg(3)Al(OH)(8).CAN . 3.1H(2)O. The overall
      release pattern of the intercalated cinnamate in the soil solution could be best
      described by the power-function equation [Formula: see text]. This suggests that
      diffusion-controlled processes besides simple ion-exchange process play an
      important role in release of the intercalated cinnamate. Furthermore, its
      behavior in a cultivated soil clearly shows that hybridization leads to
      protection of cinnamate against the degradation as well as to a controlled
      release in soils. Its antifungal activity against the growth of P. capsici in a
      potato dextrose agar medium and a red pepper seedling definitely shows that the
      hybrid is very effective in controlling the root rot of red pepper. CONCLUSION:
      This study demonstrates that the hybridization of natural antibiotic substances
      with layered double hydroxides could be a fascinating alternative for green
      formulation of pesticides. This unique hybrid system leads to the salient
      features such as protection of the substances against chemical and microbial
      degradations, controlled release, and nature compatibility. RECOMMENDATIONS AND
      PERSPECTIVES: This study suggests one of the sound strategies to make a
      breakthrough in the formulation of green pesticides. Hybridization with inorganic
      matrixes not only enables the natural antibiotic substances to replace the
      synthetic ingredients but also adjuvants to be excluded from the formulations.
      Furthermore, the resulting hybrid exhibits a controlled release of the
      intercalated substances. Although substantiated further, this study is expected
      to attract a great deal of attention to reliable application of natural
      antibiotic substances in green protection of crops and agricultural products.

PMID- 19756806
TI  - Hepatic expression of long-chain acyl-CoA synthetase 3 is upregulated in
      hyperlipidemic hamsters.
AB  - Members of the mammalian long-chain acyl-CoA synthetase (ACSL) family are key
      enzymes for cellular fatty acid metabolism that catalyze the initial step in
      activation of long-chain fatty acids. However, the specificity of individual
      isoforms of ACSL to the lipid metabolic process is not well studied. In addition,
      the regulation of expression of individual ACSL isoforms under hyperlipidemic
      conditions is largely unknown. We cloned the hamster ACSL3 cDNA coding region and
      generated specific antibodies recognizing the ACSL3 protein. We next observed the
      changes in ACSL3 mRNA and protein expression in hamsters fed a standard chow diet
      or a high fat and high cholesterol (HFHC) diet. HFHC feeding significantly
      increased ACSL3 mRNA and protein expression in liver and to a lesser extent in
      muscle but not in adipose, brain, heart, or testis. Additionally, ACSL3 mRNA
      abundance was differentially regulated by the nutritional status in different
      tissues with liver, muscle, and adipose being the most sensitive tissues.
      Importantly, the hepatic ACSL3 mRNA expression pattern in response to fasting and
      refeeding in hyperlipidemic hamsters differed from that observed in normal chow
      fed hamsters. Together, these results provide the first in vivo evidence of
      altered regulation of hepatic ACSL3 expression under hyperlipidemic conditions
      and suggest important regulatory roles for this enzyme in lipid metabolism.

PMID- 19756807
TI  - Percutaneous hemi-epiphysiodesis using transphyseal cannulated screws for genu
      valgum in adolescents.
AB  - PURPOSE: The purpose of this study was to assess percutaneous femoral distal hemi
      epiphysiodesis using transphyseal cannulated screws in order to correct valgus
      angular deformities of the knee in pediatric and adolescent patients. METHODS:
      This is a prospective longitudinal study in which our experience with 52 patients
      is described. RESULTS: We evaluated 100 knees surgically managed for pathologic
      genu valgum over a 68-month period. The average age at surgery for boys and girls
      was 14 years and 7 months (range 12.7-15.1 years) and 13 years and 6 months
      (range 12.9-14.8 years), respectively. The pre-surgical tibiofemoral (T-F) angle
      was measured at between 14.17 degrees  and 35.3 degrees , and the postoperative T
      F was measured at between 6.2 degrees  and 15.8 degrees  (7.2 degrees  +/- 0.65
      degrees , mean +/- standard deviation), for an average correction of 0.73 degrees
      +/- 0.45 degrees  per month). The mean follow-up after surgery was 3.2 years
      (range 2.3-5.3 years). CONCLUSIONS: We demonstrate a simple, fast and
      reproducible surgical technique for percutaneous epiphysiodesis with low
      morbidity, rapid rehabilitation and a rapid return to school and sports
      activities. We experienced no complications, such as overcorrection,
      undercorrection, postoperative hematoma or infection. We conclude that
      percutaneous screw epiphysiodesis is an excellent option for the treatment of
      genu valgum in adolescents.

PMID- 19756808
TI  - On quantitative effects of RNA shape abstraction.
AB  - Over the last few decades, much effort has been taken to develop approaches for
      identifying good predictions of RNA secondary structure. This is due to the fact
      that most computational prediction methods based on free energy minimization
      compute a number of suboptimal foldings and we have to identify the native
      folding among all these possible secondary structures. Using the abstract shapes
      approach as introduced by Giegerich et al. (Nucleic Acids Res 32(16):4843-4851,
      2004), each class of similar secondary structures is represented by one shape and
      the native structures can be found among the top shape representatives. In this
      article, we derive some interesting results answering enumeration problems for
      abstract shapes and secondary structures of RNA. We compute precise asymptotics
      for the number of different shape representations of size n and for the number of
      different shapes showing up when abstracting from secondary structures of size n
      under a combinatorial point of view. A more realistic model taking primary
      structures into account remains an open challenge. We give some arguments why the
      present techniques cannot be applied in this case.

PMID- 19756809
TI  - Neuroprotective molecular mechanisms of (-)-epigallocatechin-3-gallate: a
      reflective outcome of its antioxidant, iron chelating and neuritogenic
      properties.
AB  - Tea, the major source of dietary flavonoids, particularly the epicatechins,
      signifies the second most frequently consumed beverage worldwide, which varies
      its status from a simple ancient cultural drink to a nutrient component, endowed
      possible beneficial neuro-pharmacological actions. Accumulating evidence suggests
      that oxidative stress, resulting in reactive oxygen species generation, plays a
      pivotal role in neurodegenerative diseases, supporting the implementation of
      radical scavengers and metal chelating agents, such as natural tea polyphenols,
      for therapy. Vast epidemiology data indicate a correlation between occurrence of
      neurodegenerative disorders, such as Parkinson's and Alzheimer's diseases, and
      green tea consumption. In particular, recent literature strengthens the
      perception that diverse molecular signaling pathways, participating in the
      neuroprotective activity of the major green tea polyphenol, (-)-epigallocatechin
      3-gallate (EGCG), renders this natural compound as potential agent to reduce the
      risk of various neurodegenerative diseases. In the current review, we discuss the
      studies concerning the mechanisms of action implicated in EGCG-induced
      neuroprotection and discuss the vision to translate these findings into a
      lifestyle arena.

PMID- 19756810
TI  - Modulation of multiple pathways involved in the maintenance of neuronal function
      during aging by fisetin.
AB  - Multiple factors have been implicated in the age-related declines in brain
      function. Thus, it is unlikely that modulating only a single factor will be
      effective at slowing this decline. A better approach is to identify small
      molecules that have multiple biological activities relevant to the maintenance of
      brain function. Over the last few years, we have identified an orally active,
      novel neuroprotective and cognition-enhancing molecule, the flavonoid fisetin.
      Fisetin not only has direct antioxidant activity but it can also increase the
      intracellular levels of glutathione, the major intracellular antioxidant. Fisetin
      can also maintain mitochondrial function in the presence of oxidative stress. In
      addition, it has anti-inflammatory activity against microglial cells and inhibits
      the activity of 5-lipoxygenase, thereby reducing the production of lipid
      peroxides and their pro-inflammatory by-products. This wide range of actions
      suggests that fisetin has the ability to reduce the age-related decline in brain
      function.

PMID- 19756811
TI  - [Effect of increased social support on the well-being of cognitively impaired
      elderly people].
AB  - Social relationships are an important factor for maintaining life satisfaction in
      elderly people. Little is known, however, about the influence of increased social
      support towards the well-being of cognitively impaired people. This is why two
      comparative studies in Switzerland and Austria, with 84 cognitively impaired
      individuals (aged between 65 and 98) with in-patient treatment, used a control
      group design to examine whether increased social support would have a positive
      effect on the well-being of these individuals. To this end, interventions in the
      form of emotional social support through volunteer visitors for dementia patients
      were carried out. In both studies, a positive association between increased
      social support by volunteer assistants and well-being emerged. The investigations
      show that social support and attention are generally registered and perceived as
      creating a pleasantly soothing feeling in cognitively impaired people.

PMID- 19756812
TI  - [Evidence-based recommendations on primary diagnostics of peripheral arterial
      occlusive disease in geriatric patients].
AB  - The prevalence of peripheral arterial occlusive disease (PAOD) is high in elderly
      patients and its clinical manifestation is often atypical. Comorbidity and
      morbidity as a consequence of PAOD are significant. Therefore, standardized
      primary diagnostics are required among geriatric patients. Drawn from a search of
      the literature, evidence-based recommendations are provided. Pulse palpation and
      the evaluation of a patient's medical history are obligatory components of
      primary diagnostics, even in the absence of typical symptoms. In the case of
      pathological and ambiguous findings, measuring Doppler ankle pressures is
      suggested as the next diagnostic step. Further measures depend on the following
      factors: the presence of lesions on the leg with disturbed blood flow,
      predominantly in the foot and lower leg areas, degree of PAOD-related ailments,
      and, finally, intended surgery of the affected leg for other medical reasons.

PMID- 19756813
TI  - Benefits and limitations of cardiovascular pre-competition screening in
      international football.
AB  - BACKGROUND: Competitive sport can serve as a trigger for sudden cardiac death
      (SCD). The majority of athletes who die suddenly have previously unsuspected
      structural heart disease. Medical evaluation before competition offers the
      potential to identify cardiovascular abnormalities in asymptomatic athletes.
      Consensus on the ideal screening programme has not been reached. So, a
      cardiovascular pre-competition screening of elite football players was developed
      and implemented prior to the 2006 FIFA World Cup Germany to detect SCD risk
      factors. METHODS: Medical history, physical examination, 12-lead resting- and
      exercise electrocardiogram (ECG) and echocardiography results of the players were
      recorded on a standardised form by the team physicians and submitted after the
      final match for retrospective evaluation by two blinded independent cardiologic
      reviewers. RESULTS: Response rate was 82% (605 of 736 players). Completeness and
      quality of the recordings and examination methods differed amongst teams. In 25
      players (4.8%), the examining physicians evaluated the resting ECG as
      pathological. Suspicious echocardiographic findings demanding further
      investigations to rule out serious cardiovascular disease existed in 1% of the
      players. CONCLUSION: Cardiovascular pre-competition screening proved feasible in
      international elite football teams, but turned out to be vital to ensure high
      quality of data, particularly with regard to stress testing and echocardiography.
      The screening concept was revised mainly to improve completeness and quality of
      data acquisition. Resting ECG and echocardiography were retained, but it is
      questionable if exercise testing should be included in this context.

PMID- 19756814
TI  - Diagnostic performance of magnetic resonance first pass perfusion imaging is
      equally potent in female compared to male patients with coronary artery disease.
AB  - BACKGROUND: Noninvasive diagnosis of coronary artery disease (CAD) in women is
      crucial because of a lower prevalence of CAD in premenopausal women, different
      cardiac risk profile and pattern of CAD, lower exercise tolerance and more
      atypical symptoms compared to men. Therefore, we tested the diagnostic power of
      cardiac magnetic resonance first pass perfusion imaging (CMR-FPPI) for the
      diagnosis of significant coronary stenoses in females versus males. METHODS AND
      RESULTS: 256 consecutive patients, 77 females and 179 males with atypical or
      typical chest pain and intermediate risk of CAD were studied by coronary
      angiography and CMR-FPPI (1.5T Intera CV). A three-slice, short-axis perfusion
      scan with a saturation prepulse was performed during infusion of adenosine and at
      rest followed by late enhancement imaging for myocardial scar. Gadolinium-DTPA
      was administered at 0.1 mmol/kg body weight. Perfusion images were visually
      analysed, coronary stenoses by quantitative coronary angiography. Sensitivity,
      specificity and accuracy of CMR-FPPI for detection of a significant coronary
      artery stenosis (> or = 50% luminal narrowing) in the entire group were 91.3,
      81.7 and 88.6%, the corresponding values for females were 90.9, 90.6 and 90.8%
      and for males 91.4, 74.4 and 87.7%, and in the subgroup of females with suspected
      primary CAD 83.3, 96.0 and 93.6%, and for suspected progression 92.1, 71.4 and
      88.9%. CONCLUSION: Diagnostic accuracy of CMR-FPPI is very high in women with
      intermediate risk of CAD and comparable or in part superior to results in males.
      With the advantage of the absence of radiation exposure and high spatial and
      temporal resolution, CMR-FPPI has the potential to become the preferred imaging
      test to select women for coronary angiography.

PMID- 19756815
TI  - Non-invasive imaging in the diagnosis of acute viral myocarditis.
AB  - Autopsy series of consecutive cases have demonstrated an incidence of myocarditis
      at approximately 1-10%; on the contrary, myocarditis is seriously underdiagnosed
      clinically. In a traditional view, the gold standard has been myocardial biopsy.
      However, it is generally specific but invasive and less sensitive, mostly because
      of the focal nature of the disease. Thus, non-invasive approaches to detect
      myocarditis are necessary. The traditional diagnostic tools are
      electrocardiography, laboratory values, especially troponin T or I, creatine
      kinase and echocardiography. For a long period, nuclear technique with indium-111
      antimyosin antibody has been used as a diagnostic approach. In the last years,
      the use of this technique has declined because of radiation exposure and 48-h
      delay in obtaining imaging after injection to prevent blood pool effect. Thus, a
      non-invasive diagnostic approach without radiation and online image availability
      has been awaited. Cardiac magnetic resonance imaging has these promising
      characteristics. With this technique, it is possible to analyse inflammation,
      oedema and necrosis in addition to functional parameters such as left ventricular
      function, regional wall motion and dimensions. Thus, cardiovascular magnetic
      resonance imaging has emerged as the most important imaging tool in the
      diagnostic procedure and the review focus on this field. But there are also
      advances in echocardiography and computer tomography, which are described in
      detail.

PMID- 19756816
TI  - [Atrial pacing for prevention of atrial fibrillation.  Influence of septal atrial
      pacing, atrial overdrive and AV-delay-optimization on atrial fibrillation
      burden].
AB  - BACKGROUND: Atrial overdrive and optimized interatrial conduction time can reduce
      atrial fibrillation (AF). Increased ventricular stimulation results in a higher
      incidence of atrial fibrillation. PATIENTS AND METHODS: In 25 patients with
      paroxysmal AF, a dual-chamber pacemaker (Identity DR 5370, St. Jude Medical) was
      implanted. Atrial leads were placed randomly either septal (n=12) or conventional
      (n=13). Dynamic atrial overdrive (DAO) was activated and the AV delay was
      optimized according to Koglek's method. After 3, 6, 9, and 12 months automatic
      mode switch (AF burden) was analysed. RESULTS: No difference in implantation
      parameters were observed between groups. Technical implantation parameters were
      in the normal range for both groups. After 12 months patients in the septal group
      had less AF burden (1% vs. 7%, p=0.06), and the total number of AF episodes was
      reduced. CONCLUSION: Septal pacing is safe. In combination with DAO and AV delay
      optimization it may reduce the AF burden, which can be observed after 12 months.

PMID- 19756817
TI  - [Pacemaker ECG Quiz No. 20.   Multiple ventricular extrasystoles with a little
      extra].
AB  - A patient with ischemic heart disease and dual-chamber pacing for binodal
      disease, exhibiting a complex pacemaker ECG, is presented.

PMID- 19756818
TI  - [Cardiac resynchronization therapy. The electrophysiological contribution to the
      treatment of heart failure].

PMID- 19756819
TI  - Hippocampus, glucocorticoids and neurocognitive functions in patients with first
      episode major depressive disorders.
AB  - The aim of this study was to determine whether there was any relationship between
      hippocampal volume, and glucocorticoid regulation, and cognitive dysfunctions in
      drug-naive major depressive disorder (MDD) patients during their first episode.
      Twenty drug-free female MDD patients in their first episode and 15 healthy
      females as control subjects were included in the study. All subjects underwent
      3.0 Tesla (T) magnetic resonance imaging (MRI), comprehensive neuropsychological
      testing and dexamethasone suppression tests (DST). The volumes of the right and
      left hippocampus of the patients were found to be significantly smaller than
      those of the controls. Patients were found to have significantly lower scores on
      measures of attention, working memory, psychomotor speed, executive functions,
      and visual and verbal memory fields. The performance of the patients only in the
      recollection memory and memory of reward-associated rules were positively
      correlated with hippocampal volumes. The volumes of the left and right
      hippocampus did not correlate with basal or post-dexamethasone cortisol levels.
      Our findings indicate that depressed patients have smaller hippocampi even in the
      earlier phase of their illness. Further research efforts are needed to explain
      the mechanisms that are responsible for the small hippocampus in depressed
      patients.

PMID- 19756820
TI  - Brainstem raphe lesion in patients with major depressive disorder and in patients
      with suicidal ideation recorded on transcranial sonography.
AB  - Recent transcranial sonography (TCS) studies showed that disruption of echogenic
      midbrain line, corresponding to basal limbic system and raphe nuclei (RN) within,
      might represent functional marker for the development of depression. Major
      depressive disorder (MDD) is one of the most common psychiatric disorders
      associated with suicidal ideation. We initiated this study to assess the
      usefulness of TCS recording in a group of MDD patients and in MDD patients who
      also reported suicidal ideation, on the assumption that TCS might serve as a
      screening method for differentiating patients at risk of suicide. Altogether 71
      subjects: 17 patients with MDD, 14 patients with MDD who also reported suicidal
      ideation and 40 healthy controls, were studied using TCS by two independent
      physicians. Reduced raphe echogenicity was found in 8 of 17 (47%) of the patients
      with MDD but only in 6 of 40 (15%) controls. In patients with suicidal ideations
      that finding was even more pronounced (12 of 14, 86%) with the highest frequency
      of completely not visible TCS RN finding (10 of 14, 72%). Data showed that
      altered echogenicity of the RN is frequent in patients with suicidal ideation.
      Normal RN echogenicity in MDD patients was associated with less severe depressive
      symptoms and rarely with the presence of suicidal ideations. As far as we know,
      these are the first ever obtained results which show that TCS might help
      differentiating MDD patients with suicidal risk or eventually predict good
      disease recovery based on the findings of RN hypo- or normoechogenicity.

PMID- 19756821
TI  - A case of central sleep apnea strictly dependent upon REM-sleep.
AB  - Central sleep apnea (CSA) is characterized by the inability to generate regular
      breathing patterns as a result of the loss of metabolic drive and failure of
      respiratory muscle control. We present the case of a 54-year-old woman with a
      severe CSA strictly dependent upon REM-sleep. Extensive diagnostic workup
      excluded typical underlying causes and serological analysis revealed acute
      borreliosis infection. The severity of sleep apnea decreased after repeated
      polysomnographic studies without a specific therapy. CSA is usually associated
      with non-REM stages of slow-wave-sleep. This report illustrates the clinical
      presentation and diagnostic implications of an unusual case of a CSA strictly
      associated with REM-sleep. Anecdotally reports of severe respiratory failure in
      borreliosis indicate the potential of this infection to destabilize breathing
      control but the precise impact of the infection remains controversial. In our
      case, a relevant neuroborreliosis was not proven, since there were no other
      neurologic impairments and the patient refused studies of liquor fluid.

PMID- 19756822
TI  - Acquired pendular nystagmus in multiple sclerosis: an examiner-blind cross-over
      treatment study of memantine and gabapentin.
AB  - A prospective examiner-blind, cross-over study was conducted to compare the
      efficacy of memantine (40 or 60 mg/day) and gabapentin (1,200 mg/day) as therapy
      for acquired fixational pendular nystagmus (APN) in 11 patients with multiple
      sclerosis. APN was documented in 20 eyes by electrooculography (EOG). The primary
      objective of the study was an at least 50% reduction in amplitude and/or
      frequency of APN compared with baseline values in EOG. This aim was reached for
      17 of 20 APN-affected eyes with memantine 40-60 mg and for 11 eyes with
      gabapentin up to 1,200 mg. A complete cessation of APN was achieved in eight eyes
      (four patients) with memantine 40 mg and in a further four eyes (two patients)
      with memantine 60 mg. One patient achieved the same benefit with memantine 40 mg
      and gabapentin. In two other eyes APN completely subsided with gabapentin 1,200
      mg only, but not with memantine. Near visual acuity, a secondary outcome
      parameter, improved by at least 0.1 in 11 of 17 eyes treated with memantine and
      in 8 out of 16 eyes treated with gabapentin. In summary, memantine and gabapentin
      are safe and effective treatment options for APN.

PMID- 19756823
TI  - Oculomotor disorders in adult-onset Still's disease.

PMID- 19756824
TI  - Bilateral brainstem activation by thermal stimulation of the face in healthy
      volunteers.
AB  - Contralateral sensory deficits in Wallenberg's lateral medullary syndrome suggest
      bilateral processing of trigeminal afferent input in the human brainstem. On the
      basis of experiments in rodents and clinical data, the present study addresses
      the hypothesis of bilateral projection of facial nociceptive input onto the
      spinal trigeminal nucleus (STN) in healthy humans. Nociceptive processing in the
      brainstem was investigated by functional magnetic resonance imaging (fMRI) in 18
      healthy volunteers. Heat stimuli (39, 43, 46 degrees C) were applied by a Peltier
      type thermode to the left forehead (V1) and the left mental region (V3). Analyses
      of fMRI data were performed with SPM2 and BrainVoyager software. A region-of
      interest approach analyzed local activation in the STN. Heat evoked significant
      bilateral activation in the STN (P < 0.01, T > 2.8). Contralateral activation was
      more frequent during stimulation of the V1 than of the V3 region. Whereas
      activation by V1 stimulation was located in caudal STN, V3 stimulation induced
      activity in more rostral parts of the STN. Functional MRI data in humans suggest
      bilateral brainstem activation when heat is applied to the face. Contralateral
      brainstem activity is more pronounced by stimulation of V1 as compared to V3. The
      results indicate similar nociceptive processing in humans and rodents and may
      explain clinical findings.

PMID- 19756825
TI  - Predictors and outcome of acute symptomatic cerebral infarctions following
      aneurysmal subarachnoid hemorrhage.
AB  - The leading cause of unfavorable outcomes following aneurysmal subarachnoid
      hemorrhage (SAH) is cerebral infarction. In this 3-year retrospective study, we
      have retrospectively evaluated 172 hospitalized patients with aneurysmal SAH, and
      compared those who developed a complicated cerebral infarction with those who did
      not. In this study, acute symptomatic cerebral infarctions accounted for 22.6%
      (39/172) of all episodes. Significant statistical analysis between the two
      patient groups included age at onset, hypertension as the underlying disease,
      presence of symptomatic vasospasm, mean hospitalization days and Glasgow Outcome
      Score at the time of discharge. After a minimum 1.5-year follow-up period, the
      median (interquantile range) Barthel index score was 75 (6-85) for those patients
      who had cerebral infarctions, and 80 (0-90) for those who had no cerebral
      infarctions. Multiple logistic regression analysis demonstrated that the presence
      of symptomatic vasospasm was independently associated with the presence of acute
      symptomatic cerebral infarctions. The presence of symptomatic vasospasm implies
      the danger of acute symptomatic cerebral events after aneurysmal SAH. Although
      our study demonstrates a worse short-term outcome and longer duration of
      hospitalization in this special group of patients, the functional outcome for
      patients with cerebral infarction was not inferior to those patients without
      cerebral infarction after a follow-up of at least 1.5-years.

PMID- 19756826
TI  - Progressive development of augmentation during long-term treatment with levodopa
      in restless legs syndrome: results of a prospective multi-center study.
AB  - The European Restless Legs Syndrome (RLS) Study Group performed the first multi
      center, long-term study systematically evaluating RLS augmentation under levodopa
      treatment. This prospective, open-label 6-month study was conducted in six
      European countries and included 65 patients (85% treatment naive) with idiopathic
      RLS. Levodopa was flexibly up-titrated to a maximum dose of 600 mg/day. Presence
      of augmentation was diagnosed independently by two international experts using
      established criteria. In addition to the augmentation severity rating scale
      (ASRS), changes in RLS severity (International RLS severity rating scale (IRLS),
      clinical global impression (CGI)) were analyzed. Sixty patients provided
      evaluable data, 35 completed the trial and 25 dropped out. Augmentation occurred
      in 60% (36/60) of patients, causing 11.7% (7/60) to drop out. Median time to
      occurrence of augmentation was 71 days. The mean maximum dose of levodopa was 311
      mg/day (SD: 105). Patients with augmentation compared to those without were
      significantly more likely to be on higher doses of levodopa (> or =300 mg, 83 vs.
      54%, P = 0.03) and to show less improvement of symptom severity (IRLS, P =
      0.039). Augmentation was common with levodopa, but could be tolerated by most
      patients during this 6-month trial. Patients should be followed over longer
      periods to determine if dropout rates increase with time.

PMID- 19756827
TI  - Characterization of functioning in multiple sclerosis using the ICF.
AB  - The objective of this study was to explore whether it is possible to describe
      based on the International Classification of Functioning, Disability and Health
      (ICF) relevant aspects of functioning and disability affected in multiple
      sclerosis (MS) as well as environmental factors relevant to persons with MS. The
      specific aim was to identify most relevant 'Body functions', 'Body structures',
      'Activities and participation', as well as 'Environmental factors' in patients
      with MS using the ICF. Additionally, different MS forms were compared with
      respect to the identified problems. A multi-centre study was conducted in an
      empirical cross-sectional design. Data from 205 individuals with MS were
      collected in rehabilitation centres: disease related data, socio-demographic
      data, single interviews based on the Extended ICF Checklist and a patient
      questionnaire including ratings on general health and functioning status, Beck
      Depression Inventory II (BDI-II) and Comorbidity Questionnaire (SCQ). The 129 ICF
      categories identified represent a comprehensive classification of functioning in
      MS from the clinical perspective. Differences between MS forms were observed for
      several ICF categories, EDSS, general health and functioning status, but not for
      BDI and SCQ. The study showed that it is possible to describe based on the ICF
      the spectrum in functioning and disability affected in MS as well as
      environmental factors relevant to persons with MS.

PMID- 19756828
TI  - The influence of age on heart rate variability during morning wakefulness.
AB  - OBJECTIVE: Early morning wakefulness is associated with a peak in cardiac events.
      The influence of ageing on cardiac regulation during this time is unknown. This
      cross-sectional study of healthy men and women (n = 40, 20-30 and >60 years)
      investigated the effect of age on heart rate variability (HRV) during morning
      versus evening wakefulness and sleep. METHODS: Stable electrocardiogram data
      during each wake period and sleep stage was analysed using power spectral
      analysis. HRV measurements were assessed using two (young, older) by two (male,
      female) ANOVAs with repeated measures on wake/sleep stage. RESULTS: Young adults
      experienced increased low-frequency power and low-frequency/high-frequency ratios
      during morning wakefulness versus slow wave sleep (p < 0.01). Older adults did
      not show any variation in any HRV variables across wake and sleep stages. All
      effects were independent of gender. INTERPRETATION: Older adults did not
      experience increased sympathetic dominance during morning wakefulness; thus in
      the older population, fluctuations in autonomic control, indicated by HRV
      measurements, are unlikely to account for increased occurrence of cardiac events
      at this time.

PMID- 19756829
TI  - Circulating endocannabinoid concentrations during orthostatic stress.
AB  - BACKGROUND: In animals, the endocannabinoid system is activated during
      hemodynamic insults and restrains blood pressure in part through sympathetic
      inhibition. MATERIALS AND METHODS: We tested the hypothesis that hemodynamic
      stress elicited by head-up tilt testing increases systemic endocannabinoid
      concentrations in humans and that excessive endocannabinoid availability
      predisposes to presyncope. RESULTS: With head-up tilt, 2-arachidonoylglycerol
      increased, whereas anandamide remained unchanged. CONCLUSIONS: In contrast to our
      expectations, anandamide plasma concentration at rest was directly correlated
      with orthostatic tolerance, rather than intolerance.

PMID- 19756830
TI  - Hip structural geometry and incidence of hip fracture in postmenopausal women:
      what does it add to conventional bone mineral density?
AB  - SUMMARY: Hip geometry measurements of outer diameter and buckling ratio at the
      intertrochanter and shaft of the hip dual energy X-ray absorptiometry (DXA) scan
      predicted incident hip fracture in postmenopausal women. These associations,
      independent of age, body size, clinical risk factors, and conventional areal bone
      mineral density, suggest hip geometry plays a role in fracture etiology and may
      aid in improving identification of older women at high fracture risk.
      INTRODUCTION: This study examined whether hip geometry parameters predicted hip
      fracture independent of body size, clinical risk factors, and conventional
      femoral neck bone mineral density (aBMD) and whether summary factors could be
      identified to predict hip fracture. METHODS: We studied 10,290 postmenopausal
      women from the Women's Health Initiative. Eight thousand eight hundred forty
      three remained fracture free during follow-up to 11 years of follow-up, while 147
      fractured their hip, and 1,300 had other clinical fractures. Hip structural
      analysis software measured bone cross-sectional area, outer diameter, section
      modulus, average cortical thickness, and buckling ratio on archived DXA scans in
      three hip regions: narrow neck, intertrochanter, and shaft. Hazard ratios were
      estimated using Cox proportional hazards models for individual parameters and for
      composite factors extracted from principal components analysis from all 15
      parameters. RESULTS: After adjustment for age, body size, clinical risk factors,
      and aBMD, intertrochanter and shaft outer diameter measurements remained
      independent predictors of hip fracture with hazard ratios for a one standard
      deviation increase of 1.61 (95% confidence interval (CI), 1.25-2.08) for the
      intertrochanter and 1.36 (95% CI, 1.06-1.76) for the shaft. Average buckling
      ratios also independently predicted incident hip fracture with hazard ratios of
      1.43 (95% CI, 1.10-1.87) at the intertrochanter and 1.24 (95% CI, 1.00-1.55) at
      the shaft. Although two composite factors were extracted from principal
      components analysis, neither was superior to these individual measurements at
      predicting incident hip fracture. CONCLUSIONS: Two hip geometry parameters,
      intertrochanter outer diameter and buckling ratio, predict incident hip fracture
      after accounting for clinical risk factors and aBMD.

PMID- 19756831
TI  - Assessing interest in an osteoporosis website: a survey among women eligible for
      osteoporosis screening.
AB  - A survey was conducted to assess interest in an osteoporosis website. Two thirds
      of respondents indicated they would read about osteoporosis on a website, and
      half reported they might use the website more interactively. Women were receptive
      to the concept of web-based education and management of osteoporosis care.
      INTRODUCTION: As Americans increasingly use the Internet as a source for health
      information, healthcare providers continue to develop disease management and
      education websites. Providence Health & Services conducted a survey among female
      patients eligible for osteoporosis screening to assess interest in a physician
      prescribed osteoporosis website. METHODS: In 2006, a self-administered survey
      designed to assess osteoporosis status, Internet use, and the likelihood of using
      an osteoporosis website for information and disease management was sent to 3,000
      active female patients between the ages of 50 and 85 in the Portland, Oregon
      metropolitan area. RESULTS: Among 778 respondents, 80% reported having access to
      the Internet, and 70% indicated they were likely to use the Internet for health
      related information gathering. While 65% of respondents indicated they would be
      likely to read about osteoporosis on a dedicated website, only about half
      reported they might use the website for more interactive disease management
      activities such as scheduling appointments, receiving test results, or consulting
      with their physician. Both Internet access and interest in the osteoporosis
      website declined significantly with age. CONCLUSIONS: These data suggest that
      middle-aged women are moderately receptive to the concept of web-based care for
      certain components of osteoporosis management and education.

PMID- 19756832
TI  - Is there a U-shaped association between physical activity and falling in older
      persons?
AB  - This study tests whether the relationship between physical activity and
      (recurrent) falling is U-shaped. Among 1,337 community-dwelling older persons, no
      evidence for a nonlinear association was found. If all older persons increase
      their physical activity level with 100 units, 4% may be prevented to become
      recurrent fallers. INTRODUCTION: Previous studies suggest a U-shaped relationship
      between physical activity and falling. This study tests this hypothesis and
      examines whether this relationship is modified by level of physical functioning.
      METHODS: Community-dwelling persons (65+) from the Longitudinal Aging Study
      Amsterdam (LASA) were prospectively followed on falls for 3 years after baseline
      assessment in 1995/1996 (n = 1,337). Outcome measures were time to first fall and
      time to recurrent falling. The LASA Physical Activity Questionnaire was used to
      calculate physical activity in minutes per day weighted for intensity (range 0
      2000). Physical functioning was measured with physical performance tests and self
      reported functional limitations. Confounders were age, sex, body mass index,
      chronic diseases, psychotropic medication, cognitive functioning, depressive
      symptoms, and fear of falling. RESULTS: No evidence for a nonlinear association
      was found (p for physical activity(2) > 0.20). No significant association was
      found between physical activity and time to first fall. An increase in physical
      activity of 100 units led to a 4% decrease in risk of recurrent falling (adjusted
      hazard ratio 0.96, 95% confidence interval 0.92, 0.99). No interactions with
      physical performance or functional limitations were found (p > 0.50).
      CONCLUSIONS: The hypothesized U-shaped relationship between physical activity and
      falling could not be confirmed. At higher levels of physical activity, the risk
      of recurrent falling decreased, while no association was found with fall risk.

PMID- 19756833
TI  - Measurement uncertainty of 25-OH vitamin D determination with different
      commercially available kits: impact on the clinical cut offs.
AB  - SUMMARY: Due to "measurement uncertainty", the "true" 25-OH vitamin D (25(OH)D)
      of a patient (whatever the commercially available assay tested) will be >80
      nmol/L if its measured concentration is >100 nmol/L. Thus, if a physician
      considers that a normal VTD status is a 25(OH)D level >or=80 nmol/L, he should
      ensure that the patient's results are >or=100 nmol/L. INTRODUCTION: Many experts
      recommend that serum levels of 25(OH)D should be above a lower normal limit of 75
      80 nmol/L. However, the value delivered by laboratories is only an estimation of
      the "true" value due to "measurement uncertainty." When using a cut off,
      measurement uncertainty around the cut off is important because therapeutic
      actions may differ if the measured value is below or above the limit. We aimed to
      establish the "measurement uncertainty" at different levels of concentration for
      several commercially available 25(OH)D analytical techniques. METHODS: We
      constituted three pools of serum with different 25(OH)D concentrations. Each pool
      was assayed in triplicate during 5 days with the DiaSorin RIA, Liaison, Elecsys,
      and Chromsystems-HPLC assays. RESULTS: We report a relatively high "measurement
      uncertainty" for the measurement of 25(OH)D for the four different techniques:
      the mean relative uncertainties, all techniques confounded were 19.4%, 16.0%, and
      11.3% for pool 1 (35.3 nmol/L), pool 2 (79.5 nmol/L), and pool 3 (126.1 nmol/L),
      respectively. CONCLUSIONS: Our results show that, whatever the assay, the "true"
      25(OH)D of a patient will be >80 nmol/L if its measured concentration is >100
      nmol/L. In other words, if a physician considers that a normal VTD status is
      defined by a 25(OH)D level >or=80 nmol/L, he should ensure that the patients
      present a 25(OH)D >or=100 nmol/L.

PMID- 19756834
TI  - Fifteen-year experience of pediatric-onset mixed connective tissue disease.
AB  - The aim of this study was to investigate the initial clinical manifestations,
      laboratory data, complications, and outcomes of patients with pediatric-onset
      mixed connective tissue disease (MCTD) in Taiwan. We reviewed medical charts of
      patients younger than 18 years with a diagnosis of mixed connective tissue
      disease based on the criteria of Kasukawa (1) at the pediatric department of
      National Taiwan University Hospital from 1993 to 2008. A total of 12 patients
      were included. All of the patients were female. The mean age at disease onset was
      10.7 years (range 6.5 to 14 years). The most common symptoms at disease onset
      were polyarthritis (7/12 patients) and Raynaud's phenomenon (7/12 patients). The
      clinical symptoms changed with time, and other symptoms encompassing the criteria
      for MCTD developed sequentially. Inflammatory manifestations (arthritis, fever,
      and skin rash) improved following treatment, whereas sclerodermatous features
      (sclerodactyly, esophageal disease, and vasculopathy) persisted and were often
      unresponsive to therapy. The organ involvement-free rates at 2 years, 5 years,
      and 10 years were 91.7%, 78.6%, and 52.4%, respectively. In this retrospective
      study, sclerodermatous changes of internal organs were a poor prognostic factor
      in our population, and we emphasize that long-term follow-up is necessary, and
      appropriate treatment should be applied to improve the outcomes.

PMID- 19756835
TI  - Discontinuation of etanercept in patients with rheumatoid arthritis who were in
      clinical remission.
AB  - The appearance of tumor necrosis factor blockers changes the treatment goal of
      rheumatoid arthritis (RA) to include not only the inhibition of bone destruction,
      but also the induction of remission. We, herein, report two cases with RA that
      showed a prolonged remission after the discontinuation of etanercept. The two
      cases were 27 and 38 years of age, and their disease durations were 6 and 14
      months, respectively. Their disease activity score 28 (DAS28) before treatment
      were 4.43 and 5.07, respectively. Case two was resistant to infliximab as
      determined by previous treatment with this therapy. Both cases showed a dramatic
      clinical response and discontinued etanercept in the 15th month and the 14th
      month after the start of treatment, respectively. No exacerbation of arthritis
      was evident after the discontinuation of etanercept as supported by the
      maintenance of DAS28 at less than 2.6. Moreover, after the discontinuation of
      etanercept, radiographic progression was not evident and decreased modified Sharp
      scores were observed for at least 1 year in both cases. These findings indicate
      that clinical and radiographic remission is possible in some patients with RA
      after the discontinuation of etanercept.

PMID- 19756836
TI  - A pseudoleukemic blood differentiation in a 13-year-old child: an extraordinary
      presentation of Churg-Strauss syndrome.
AB  - Churg-Strauss syndrome (CSS) is a rare systemic vasculitis of the small- and
      medium-size vessels. It is mostly seen in elderly patients presenting as de novo
      asthma, eosinophilia, and vasculitic organ involvement. In childhood, CSS is
      extremely rare. The course of pediatric CSS is usually severe and often lethal.
      We present a case of a 13-year-old girl with a short history of asthma, marked
      eosinophilia, and multiorgan involvement. The extremely high level of blood
      eosinophilic granulocytes (51.6 * 10(9)/L) prompted a workup for eosinophilic
      leukemia before the diagnosis CSS could be made. Subsequently, the disease was
      successfully treated. This case report shows a classical case of childhood CSS,
      remarkable because of the presence of extreme hypereosinophilia. It underlines
      the importance of CSS as a life-threatening cause of hypereosinophilia in
      children.

PMID- 19756837
TI  - Advantages and esthetic results of erbium, chromium:yttrium-scandium-gallium
      garnet laser application in second-stage implant surgery in patients with
      insufficient gingival attachment: a report of three cases.
AB  - Traditional implant placement involves two surgical stages. Although the second
      stage is comparatively less aggressive for the patient, postoperative pain and
      swelling can be further reduced by the use of laser instead of a scalpel. Correct
      handling of peri-implant soft tissue is of major importance in obtaining adequate
      gingival tissue attachment around implants. The presence of this keratinized
      gingiva ensures adequate esthetic results and maintains implant health. We report
      on three patients with implants in the anterior area who were operated on under
      the above conditions. Traditionally, the tissue overlying the implants is removed
      and eliminated. In seeking a way to preserve the attached gingiva, we raised a
      trapezoidal flap, uncovering each implant and allowing apical repositioning and
      transpositioning of keratinized gingiva to the buccal side. The results obtained
      were compared with those from other patients operated on by conventional scalpel.
      The erbium, chromium:yttrium-scandium-gallium-garnet (Er,Cr:YSGG) laser minimized
      postoperative pain, and the time to prosthetic rehabilitation was also shortened.
      The esthetic results were far superior, and no complications were recorded.

PMID- 19756838
TI  - Apoptosis- and necrosis-induced changes in light attenuation  measured by optical
      coherence tomography.
AB  - Optical coherence tomography (OCT) was used to determine optical properties of
      pelleted human fibroblasts in which necrosis or apoptosis had been induced. We
      analysed the OCT data, including both the scattering properties of the medium and
      the axial point spread function of the OCT system. The optical attenuation
      coefficient in necrotic cells decreased from 2.2 +/- 0.3 mm(1) to 1.3 +/- 0.6 mm(
      1), whereas, in the apoptotic cells, an increase to 6.4 +/- 1.7 mm(-1) was
      observed. The results from cultured cells, as presented in this study, indicate
      the ability of OCT to detect and differentiate between viable, apoptotic, and
      necrotic cells, based on their attenuation coefficient. This functional
      supplement to high-resolution OCT imaging can be of great clinical benefit,
      enabling on-line monitoring of tissues, e.g. for feedback in cancer treatment.

PMID- 19756839
TI  - Provision of general paediatric surgical services in a regional hospital.
AB  - BACKGROUND: In Ireland, specialist paediatric surgery is carried out in
      paediatric hospitals in Dublin. General surgeons/consultants in other surgical
      specialities provide paediatric surgical care in regional centres. There has been
      a failure to train general surgeons with paediatric skills to replace these
      surgeons upon retirement. AIM: To assess paediatric surgical workload in one
      regional centre to focus the debate regarding the future provision of general
      paediatric surgery in Ireland. METHODS: Hospital in-patient enquiry (HIPE) system
      was used to identify total number of paediatric surgical admissions and
      procedures. Cases assessed requiring hospital transfer. RESULTS: Of 17,478
      surgical patients treated, 2,584 (14.8%) were under 14 years. A total of 2,154
      procedures were performed. CONCLUSION: Regional centres without dedicated
      paediatric surgeons deliver care to large numbers of paediatric patients. The
      demand for care highlights the need for formal paediatric services/appropriate
      surgical training for general surgical trainees.

PMID- 19756840
TI  - The repertoire and evolution of ATP-binding cassette systems in Synechococcus and
      Prochlorococcus.
AB  - Synechococcus and Prochlorococcus have made great contributions to earth's
      photosynthetic biomass. ATP-binding cassette (ABC) protein systems have been
      characterized to play important roles in various physiological functions,
      including carbon fixation, phosphate assimilation, and vitamin B(12) metabolism.
      In this study, the repertoire and domain architectures of ABC systems in
      Synechococcus and Prochlorococcus, as well as their potential evolutionary
      mechanism, have been surveyed extensively. Comparative analysis revealed an
      uneven phylogenetic distribution of the ABC systems in these organisms, and in
      particular that fresh-water Synechococcus strains contain more ABC systems than
      those of marine ones. Phylogenetic analysis indicated that lineage-specific gene
      expansion and duplication may be the important forces driving the variability of
      ABC systems in fresh-water Synechococcus and such an expansion was likely to be
      relevant to their ecological tolerance. At the domain level, ATP-binding domains
      in several ABC systems were found to fuse with many additional domains after the
      divergence from their common ancestor, indicating the versatile functions of ABC
      systems in cyanobacteria. Subsequently, 19 ABC system families were deduced to be
      the core set of ABC systems conserved in all marine-living Synechococcus and
      Prochlorococcus. In conclusion, the comprehensive survey of ABC systems in
      Synechococcus and Prochlorococcus provides novel insights into their potential
      evolutionary mechanism and the basis for further investigation of their
      physiological roles.

PMID- 19756841
TI  - Impact of the use of fluvalinate on different types of beeswax from Spanish
      hives.
AB  - Acaricides are applied in agriculture as phytosanitary products against pests and
      in apiculture to control the bee parasite Varroa destructor. Poor apicultural
      practices could result in an accumulation of residues in honeybees, in the
      environment, and in beeswax and other bee products by migration from the wax comb
      into stored honey through a process of diffusion and consequently constitute a
      potential risk for humans. In this study, six different types of beeswax samples
      were analysed for the determination of residues of fluvalinate, coumaphos, and
      bromopropylate and its metabolite 4,4'-dibromobenzophenone, all of which are the
      most commonly acaricides used by Spanish beekeepers against V. destructor. The
      analytic method consists of solid-phase extraction on a SPE Florisil cartridge
      and high-performance liquid chromatography separation using a photo diode array
      detector. The results show that fluvalinate residues were detected in 36.3% of
      samples, ranging from 1.2 to 6.6 microg/g wax. Residues of coumaphos,
      bromopropylate, and 4,4'-dibromobenzophenone were not found to be greater than
      their detection limits. This study indicates that the analysis of these compounds
      in beeswax samples could be used as bioindicators of fluvalinate sanitary
      treatment and handling practices applied by beekeepers.

PMID- 19756842
TI  - Effects of a chemically polluted discharge on the relationship between fecundity
      and parasitic infections in the chub (Leuciscus cephalus) from a river in
      southern England.
AB  - In fish there is a close association between endocrine and immune function that
      during seasonal changes in reproductive status can affect the fishes
      susceptibility to parasitic infection. The effects of endocrine-disrupting
      pollution on this association are not known. The present study investigates the
      effects of a chemically polluted (ammoniacal nitrogen, zinc, bromide) discharge
      in Cranleigh Waters, a river in southern England, on the fecundity and parasitism
      of chub, Leuciscus cephalus, over an 18-month period. In the polluted site, the
      gonado-somatic index (GSI) of fish was lower in females and higher in males
      compared to an unpolluted upstream site, indicating an androgenic effect on
      reproduction. Parasite species richness, especially the intestinal helminths
      Proteocephalus torulosus and Pomphorynchus laevis, was increased in fish in the
      polluted site. However, the occurrence of the two most common parasite species in
      the river-Myxobulus sp. 1, a gill myxozoan, and Diplostomum sp., a trematode
      found in the eye-was unchanged between polluted and unpolluted river sites.
      Nevertheless, there was a significant relationship between GSI and the prevalence
      of these two parasite species in the unpolluted site but not the polluted site
      suggesting that endocrine disruption of reproduction did not lead to an increase
      in host susceptibility. The reasons for this are discussed.

PMID- 19756843
TI  - Vitamin C and resveratrol supplementation to rat dams treated with di(2
      ethylhexyl)phthalate: impact on reproductive and oxidative stress end points in
      male offspring.
AB  - This study was carried out to assess the influence of di(2-ethylhexyl)phthalate
      (DEHP) alone or associated with antioxidants on the male reproductive system in
      newborn rats, emphasizing the implications of oxidative stress and hormonal
      balance during prenatal and early postnatal periods. Wistar females were exposed
      by oral route to DEHP alone or associated with antioxidants from gestational day
      7 to lactational day 2 according to the following treatment regimens: (C) vehicle
      control (canola oil + 1% Tween-80); (V) vitamin C (200 mg/kg) + canola oil; (R)
      resveratrol (10 mg/kg) + canola oil; (D) DEHP (500 mg/kg) + 1% Tween-80; (DV)
      DEHP (500 mg/kg) + vitamin C (200 mg/kg); and (DR) DEHP (500 mg/kg) + resveratrol
      (10 mg/kg). Two male pups per litter were randomly selected and necropsied on
      postnatal day 2. The brain and liver were removed and weighed and anogenital
      distance (AGD) was measured. Additionally, the testes were removed for assessment
      of intratesticular testosterone levels and histopathology; the liver was used to
      measure biomarkers of oxidative stress. Vitamin C and resveratrol alone did not
      affect the reproductive end points and did not induce oxidative stress. Exposure
      of dams to DEHP alone and associated with antioxidants resulted in hepatomegaly
      in offspring and significantly increased the incidence of multinucleated
      gonocytes in seminiferous cords. Testosterone and AGD presented a trend to
      decrease in DEHP-exposed groups. Catalase activity increased only in groups
      exposed to DEHP associated with antioxidants, although GST (gluthatione-S
      transferase) activity decreased in all DEHP-exposed groups. The levels of
      hydroperoxides increased only in group exposed to DEHP associated with vitamin C.
      These results indicate that the association of DEHP with antioxidants was unable
      to ameliorate DEHP-induced reproductive changes, and the coadministration of DEHP
      and these antioxidants might even contribute to an overall increase in oxidative
      stress.

PMID- 19756844
TI  - Effects of elevated nitrate concentration on mortality, growth, and egestion
      rates of Gammarus pseudolimnaeus amphipods.
AB  - There is relatively little known about nitrate toxicity in aquatic invertebrates,
      especially sublethal effects of elevated nitrate. We exposed the amphipod
      Gammarus pseudolimnaeus to elevated nitrate concentrations (up to 128 mg NO(3)
      N/L) in a laboratory experiment and measured mortality, growth rates, egestion
      rates, molting, and C:N ratio. Nitrate concentration did not affect mortality,
      egestion rate, molting, and C:N ratio. Amphipod growth decreased slightly with
      increasing nitrate concentration based on the results of a linear regression, but
      a one-way ANOVA suggested that mean growth rates were not different among nitrate
      treatments. We suggest that additional research is needed on the sublethal
      effects of elevated nitrate concentration on aquatic invertebrates, particularly
      for those taxa that have demonstrated sensitivity to other chemical stressors.

PMID- 19756845
TI  - Mass loadings of triclosan and triclocarbon from four wastewater treatment plants
      to three rivers and landfill in Savannah, Georgia, USA.
AB  - Triclosan (TCS) and triclocarbon (TCC) are bactericides used in various consumer
      and personal-care products. Recent studies have revealed considerable levels of
      these bactericides in wastewater, aquatic wildlife, and human samples.
      Consequently, in this study we measured TCS and TCC in influent and effluent,
      sludge, and pond water/sediment samples from four wastewater treatment plants
      (WWTPs) and three major rivers in Savannah, Georgia (USA). Among these treatment
      plants, the Wilshire plant showed elevated concentrations of TCS (influent,
      86,161; effluent, 5370 ng/L), whereas TCC was greater in the Georgetown plant
      (influent, 36,221) and the Wilshire plant effluent (3045 ng/L). Clearance of TCS
      and TCC were 95 and 92%, respectively, in the President Street plant, 94 and 85%,
      respectively, in the Wilshire plant, 99 and 80%, respectively, in the Travis
      Field plant, and 99 and 99%, respectively, in the Georgetown plant. Based on the
      mass flow estimate, 138 g/day of TCS and 214 g/day TCC are released into the
      Savannah River from the President Street, Travis Field, and Wilshire plants and
      1.60 g/day TCS and 1.64 g/day TCC are released to the Ogeechee River from the
      Georgetown plant. Based on the sludge data, the loading estimate can be
      calculated that 32 and 0.004 g/day TCS and 53 and 0.01 g/day TCC (nonincinerated
      and incinerated, respectively) are deposited in landfill from the President
      Street plant alone, whereas 4.6, 26, and 6.8 g/day TCS and 3.8, 23, and 5.9 g/day
      TCC (wet sludge) were produced and dumped in landfill from the rest of the WWTPs.
      Incineration of wet sludge can eliminate 99.99% of TCS and TCC. Concentrations of
      TCS and TCC in water and sediment were greater in the Vernon River, followed by
      the Savannah River and the Ogeechee River.

PMID- 19756846
TI  - Phosphate-solubilizing and plant-growth-promoting Pseudomonas aeruginosa PS1
      improves greengram performance in quizalafop-p-ethyl and clodinafop amended soil.
AB  - The quizalafop-p-ethyl- and clodinafop-tolerant phosphate-solubilizing and plant
      growth-promoting Pseudomonas aeruginosa PS1 isolated from the rhizospheric soils
      of mustard was used to determine its phosphate-solubilizing activity and other
      plant-growth-promoting traits both in the presence and absence of technical grade
      quizalafop-p-ethyl and clodinafop under in vitro conditions. Quizalafop-p-ethyl
      (at 40, 80, and 120 ppb) and clodinafop (at 400, 800, and 1200 ppb) reduced the P
      solubilizing activity, synthesis of indole-3-acetic acid, and siderophores
      progressively with increasing concentrations of each herbicide. Hydrogen cyanide
      and ammonia synthesisized by this strain, however, did not change. Furthermore,
      the effects of three concentrations each of quizalafop-p-ethyl [40 (recommended
      dose), 80, and 120 ppb] and clodinafop [400 (recommended dose), 800, and 1200
      ppb] were evaluated on plant-growth-promoting Pseudomonas aeruginosa strain PS1
      inoculated greengram plants, grown in sandy clay loam soil. Generally, all of the
      concentrations of both quizalafop-p-ethyl and clodinafop showed phytotoxicity and
      severely affected the growth, symbiosis, grain yield, and nutrient uptake by
      greengram plants. The toxicity of quizalafop-p-ethyl and clodinafop enhanced
      gradually with the increase in the dose rate of herbicides. Quizalafop-p-ethyl
      was more toxic than clodinafop. In contrast, herbicide-tolerant P. aeruginosa
      strain PS1 when used with herbicides increased the measured parameters at all
      concentrations. Both quizalafop-p-ethyl at 120 ppb and clodinafop at 400 ppb
      increased total chlorophyll content, leghemoglobin, root N, shoot N, root P,
      shoot P, seed yield, and seed protein, relative to the uninoculated control. The
      study suggests that the phytotoxicity of herbicides to legumes could be reduced
      by applying the growth-promoting herbicide-tolerant strain of Pseudomonas
      aeruginosa PS1.

PMID- 19756847
TI  - Long-term phosphorus fertilization impacts soil fungal and bacterial diversity
      but not AM fungal community in alfalfa.
AB  - Soil function may be affected by cropping practices impacting the soil microbial
      community. The effect of different phosphorus (P) fertilization rates (0, 20, or
      40 kg P(2)O(5) ha(-1)) on soil microbial diversity was studied in 8-year-old
      alfalfa monocultures. The hypothesis that P fertilization modifies soil microbial
      community was tested using denaturing gradient gel electrophoresis and
      phospholipids fatty acid (PLFA) profiling to describe soil bacteria, fungi, and
      arbuscular mycorrhizal (AM) fungi diversity. Soil parameters related to fertility
      (soil phosphate flux, soluble P, moisture, phosphatase and dehydrogenase assays,
      and carbon and nitrogen content of the light fraction of soil organic matter)
      were also monitored and related to soil microbial ribotype profiles. Change in
      soil P fertility with the application of fertilizer had no effect on crop yield
      in 8 years, but on the year of this study was associated with shifts in the
      composition of fungal and bacterial communities without affecting their richness,
      as evidenced by the absence of effect on the average number of ribotypes
      detected. However, variation in soil P level created by a history of differential
      fertilization did not significantly influence AM fungi ribotype assemblages nor
      AM fungi biomass measured with the PLFA 16:1omega5. Fertilization increased P
      flux and soil soluble P level but reduced soil moisture and soil microbial
      activity, as revealed by dehydrogenase assay. Results suggest that soil P
      fertility management could influence soil processes involving soil
      microorganisms. Seasonal variations were also recorded in microbial activity,
      soil soluble P level as well as in the abundance of specific bacterial and fungal
      PLFA indicators of soil microbial biomass.

PMID- 19756849
TI  - Nonrandom assembly of bacterial populations in activated sludge flocs.
AB  - The aim of this work was to investigate the dynamics of assembly of bacterial
      populations in activated sludge flocs. We approached this question by following
      the development of active bacterial populations during floc development in four
      replicated lab-scale activated sludge reactors, in which solid retention time
      (SRT) was set at 4 days. The null hypothesis was that the similarities in
      community composition could be accounted for by the probability that the same
      organisms occur in more than one replicated reactor. Microscopic imaging showed
      that the size of flocs in reactors with biomass retention increased during the
      first few days until a steady-state size was reached. The diversity and community
      structure of the sludge in all reactors were analyzed during a period of up to
      ten SRT, using denaturing gradient gel electrophoresis (DGGE) of reverse
      transcription polymerase chain reaction-amplified 16S rRNA. High rates of change
      in DGGE profiles from consecutive sampling points suggested a high level of
      dynamics in all reactors. This conclusion was confirmed by the application of the
      Raup and Crick probability-based similarity index (S(RC)) for the comparison of
      rRNA-based fingerprinting patterns, which indicated that bacterial communities
      within reactors were not significantly similar after three SRT (0.05 < S(RC) <
      0.95) and became significantly dissimilar after five SRT (S(RC) < 0.05). More
      importantly, significant similarity between replicate reactors was observed at
      all times analyzed (S(RC) > 0.95). The fact that the patterns between replicates
      were more reproducible than expected by chance under highly dynamic conditions
      allowed us to reject the null hypothesis that activated sludge floc communities
      assemble randomly from the available source pool of bacteria. We suggest that
      communities progressively recruit from the available pool of bacterial species,
      each with particular ecological requirements that determine their time of
      emergence into the community.

PMID- 19756850
TI  - Relationship of atmospheric pollution characterized by gas (NO2) and particles
      (PM10) to microbial communities living in bryophytes at three differently
      polluted sites (rural, urban, and industrial).
AB  - Atmospheric pollution has become a major problem for modern societies owing to
      its fatal effects on both human health and ecosystems. We studied the
      relationships of nitrogen dioxide atmospheric pollution and metal trace elements
      contained in atmospheric particles which were accumulated in bryophytes to
      microbial communities of bryophytes at three differently polluted sites in France
      (rural, urban, and industrial) over an 8-month period. The analysis of bryophytes
      showed an accumulation of Cr and Fe at the rural site; Cr, Fe, Zn, Cu, Al, and Pb
      at the urban site; and Fe, Cr, Pb, Al, Sr, Cu, and Zn at the industrial site.
      During this study, the structure of the microbial communities which is
      characterized by biomasses of microbial groups evolved differently according to
      the site. Microalgae, bacteria, rotifers, and testate amoebae biomasses were
      significantly higher in the rural site. Cyanobacteria biomass was significantly
      higher at the industrial site. Fungal and ciliate biomasses were significantly
      higher at the urban and industrial sites for the winter period and higher at the
      rural site for the spring period. The redundancy analysis showed that the physico
      chemical variables ([NO(2)], relative humidity, temperature, and site) and the
      trace elements which were accumulated in bryophytes ([Cu], [Sr], [Pb]) explained
      69.3% of the variance in the microbial community data. Moreover, our results
      suggest that microbial communities are potential biomonitors of atmospheric
      pollution. Further research is needed to understand the causal relationship
      underlined by the observed patterns.

PMID- 19756851
TI  - Peripheral zone prostate cancer. Pre-treatment evaluation with MR and 3D 1H MR
      spectroscopic imaging: correlation with pathologic findings.
AB  - The purpose of this study was to retrospectively characterize benign and
      malignant prostate peripheral zone tissue by using endorectal MRI and 3D 1H MRS.
      Fifty-two men with untreated biopsy-proven prostate cancer underwent combined
      endorectal MRI and MRSI. Whole-mount step-section histopathologic analysis
      constituted the reference standard. Biopsy correctly detected 74 locations; MRI
      correctly detected 72 locations; MRS correctly detected 72 locations; MRI + MRS
      correctly detected 78 locations. Cohen's test showed that biopsy had a lower
      degree of agreement with histology than MRI + MRS combined. The ratio of [(Cho +
      Cr)]/Cit correlates with the pathologic Gleason score. The addition of 3D1H MRSI
      to MRI can improve diagnosis of prostate cancer contributing indirectly to
      improve local staging. In addition, the correlation between metabolic 3D1H MRSI
      data with pathological Gleason grade may offer a non-invasive means to better
      predict prostate cancer aggressiveness.

PMID- 19756853
TI  - Three-dimensional CT enterography using oral gastrografin in patients with small
      bowel obstruction: comparison with axial CT images or fluoroscopic findings.
AB  - BACKGROUND: To evaluate the feasibility of 3D CT enterography using oral
      gastrografin in patients with small bowel obstruction (SBO), focusing on
      improving diagnostic performance as compared with the use of axial CT imagings
      and fluoroscopic findings. MATERIAL AND METHODS: For a 10-month period, 18
      patients with known SBO detected clinically and radiologically were enrolled. In
      all patients, gastrografin was ingested prior to CT enterography. Twelve patients
      underwent a fluoroscopic examination. Images were randomly assessed for
      confidence for the level, for the cause of SBO, and for the assessment of the
      interpretability of each image by two gastrointestinal radiologists. The results
      were considered statistically significant using the Wilcoxon rank sum test.
      RESULTS: All patients (100%) well tolerated the administration of oral
      gastrografin. The use of 3D CT enterography significantly improved diagnostic
      confidence for the interpretation of the level, cause of SBO, and the assessment
      of the interpretability of each image as compared with the use of axial CT images
      (P < 0.05). 3D CT enterography was superior as compared to fluoroscopic
      examination (P < 0.05). CONCLUSION: The use of gastrografin for 3D CT
      enterography is a safe and feasible technique for precise evaluation of known or
      suspected SBO.

PMID- 19756855
TI  - An uncommon complication of septorhinoplasty, acute dacryocystitis.
AB  - During septorhinoplasty procedures lacrimal drainage systems are susceptible to
      injury because of the close relationship of the nasal bones. Most of the injuries
      to the system remain asymptomatic. Here we report a case of septorhinoplasty
      which was complicated by acute dacryocystitis postoperatively. The patient was
      treated successfully with appropriate medical therapy.

PMID- 19756856
TI  - Using liposuction for late complication of Trachinus draco envenomation.

PMID- 19756857
TI  - Regarding the remote-knot technique.

PMID- 19756858
TI  - Quantifying the effect of ecological restoration on soil erosion in China's Loess
      Plateau region: an application of the MMF approach.
AB  - Land degradation due to erosion is one of the most serious environmental problems
      in China. To reduce land degradation, the government has taken a number of
      conservation and restoration measures, including the Sloping Land Conversion
      Program (SLCP), which was launched in 1999. A logical question is whether these
      measures have reduced soil erosion at the regional level. The objective of this
      article is to answer this question by assessing soil erosion dynamics in the Zuli
      River basin in the Loess Plateau of China from 1999 to 2006. The MMF (Morgan,
      Morgan and Finney) model was used to simulate changes in runoff and soil erosion
      over the period of time during which ecological restoration projects were
      implemented. Some model variables were derived from remotely sensed images to
      provide improved land surface representation. With an overall accuracy rate of
      0.67, our simulations show that increased ground vegetation cover, especially in
      forestlands and grasslands, has reduced soil erosion by 38.8% on average from
      1999 to 2006. During the same time period, however, the change in rainfall
      pattern has caused a 13.1% +/- 4.3% increase in soil erosion, resulting in a net
      25.7% +/- 8.5% reduction in soil erosion. This suggests that China's various
      ecological restoration efforts have been effective in reducing soil loss.

PMID- 19756859
TI  - Predicting morbidity and mortality after hepatic resection in patients with
      hepatocellular carcinoma: the role of Model for End-Stage Liver Disease score.
AB  - BACKGROUND: The Model for End-Stage Liver Disease (MELD) score is currently used
      as a disease severity index of cirrhotic patients awaiting liver transplantation.
      This study evaluated the usefulness of the MELD score in predicting mortality and
      morbidity of patients with hepatocellular carcinoma (HCC) undergoing hepatic
      resection. METHODS: The study cohort consisted of 1,017 patients who underwent
      hepatic resection for HCC between 1991 and 2005. Patient variables were examined
      by univariate and multivariate analyses to identify risk factors for morbidity
      and mortality. Accuracy in predicting mortality was assessed with the area under
      the receiver operator characteristic curve (AUC) analysis. RESULTS: The morbidity
      and mortality rates were 30.7% and 1.9%, respectively. Age, liver cirrhosis,
      operation time, and MELD score were risk factors for mortality, whereas
      indocyanine green retention rate at 15-min value, operation time, blood loss, and
      Child-Turcotte-Pugh score were risk factors for morbidity. Patients with MELD
      score >8 had higher mortality (4.0% vs. 0.6%, p = 0.004) and higher liver-related
      morbidities (16.1% vs. 4.3%, p < 0.001), including massive ascites, intra
      abdominal hemorrhage, and hepatic failure, compared with patients with MELD score
      <6. High MELD score also was related to longer postoperative hospital stay (score
      >8, 14.5 days vs. score <6, 12.6 days, p = 0.015). The AUC for MELD score as a
      predictor of mortality was 0.718, indicating high clinical usefulness.
      CONCLUSIONS: The MELD score relates with mortality and liver-related morbidities
      in HCC patients who undergo hepatic resection. A MELD score >8 represents the
      trigger for intensive treatment to improve patient outcome.

PMID- 19756860
TI  - Adhesional small bowel obstruction in the absence of previous operations:
      management and outcomes.
AB  - BACKGROUND: The majority of small bowel obstructions (SBO) are the result of
      adhesions caused by a previous abdominal operation. On rare occasions, adhesional
      SBO occurs in the absence of such an operation. Our objective was to describe the
      management, findings, and outcomes of unexplained adhesional SBO (UA-SBO) and
      examine whether preoperative diagnostic uncertainty leads to delays in therapy
      and complications. METHODS: The medical records of all adhesional SBO patients
      admitted to the Massachusetts General Hospital between January 1, 1997 and
      December 31, 2007 were screened. UA-SBO records were reviewed in detail. Each UA
      SBO patient was matched with an adhesional SBO patient with abdominal surgical
      history (SH-SBO) according to gender, age (+/-7 years), white blood cell count
      (+/-3000/mm3), time interval from the onset of symptoms to the time of admission
      (+/-24 h), and year of admission (+/-4 years). Outcomes included time from
      admission to operation, morbidity, mortality, and length of hospital stay.
      RESULTS: Of 1,036 patients with adhesional SBO, 34 (3.3%) had UA-SBO.
      Adhesiolysis was sufficient in 31 patients, whereas 3 required an enterectomy. UA
      SBO patients were similar in terms of demographics, clinical presentation, and
      initial laboratory tests with SH-SBO patients. There was no difference in any of
      the outcomes between the two groups. CONCLUSIONS: In this study of UA-SBO,
      diagnostic delays were not found and patient outcomes were similar to those of
      patients with SH-SBO.

PMID- 19756861
TI  - Resolution of hepatic encephalopathy following hepatic artery embolization in a
      patient with well-differentiated neuroendocrine tumor metastatic to the liver.
AB  - Hepatic encephalopathy is considered a contraindication to hepatic artery
      embolization. We describe a patient with a well-differentiated neuroendocrine
      tumor metastatic to the liver with refractory hepatic encephalopathy and normal
      liver function tests. The encephalopathy was refractory to standard medical
      therapy with lactulose. The patient's mental status returned to baseline after
      three hepatic artery embolization procedures. Arteriography and ultrasound
      imaging before and after embolization suggest that the encephalopathy was due to
      arterioportal shunting causing hepatofugal portal venous flow and portosystemic
      shunting. In patients with a primary or metastatic well-differentiated
      neuroendocrine tumor whose refractory hepatic encephalopathy is due to
      portosystemic shunting (rather than global hepatic dysfunction secondary to tumor
      burden), hepatic artery embolization can be performed safely and effectively.

PMID- 19756862
TI  - The march of extrahepatic collaterals: analysis of blood supply to hepatocellular
      carcinoma located in the bare area of the liver after chemoembolization.
AB  - The purpose of this study was to evaluate changes in vascular supply to
      hepatocellular carcinoma (HCC) located in the bare area of the liver in patients
      who were mainly treated with chemoembolization. Twenty-six patients with HCC
      showing a mean diameter of 3.1 +/- 1.4 cm (mean +/- standard deviation) were
      mainly treated with chemoembolization. All patients underwent 2.7 +/- 2.3
      chemoembolization sessions over 40.1 +/- 25.2 months. Tumor feeding branches
      demonstrated in each chemoembolization session were retrospectively evaluated.
      Initially, 18 tumors (59.2%) were supplied by the hepatic artery (H) and 8
      (30.8%) by both the hepatic and the extrahepatic arteries (H + C). Fourteen
      tumors (53.8%) recurred at the posterior aspect of the tumor and were supplied by
      H (n = 4), H + C (n = 5), and extrahepatic collaterals (C) (n = 5). Several
      tumors recurred despite repeated chemoembolization, and these were supplied by H
      (n = 1), H + C (n = 7), and C (n = 2) at the second recurrence, by H (n = 1), H +
      C (n = 2), and C (n = 3) at the third, by H + C (n = 2) and C (n = 2) at the
      fourth, by H + C (n = 2) and C (n = 2) at the fifth, and by H (n = 1) and C (n =
      1) at the sixth. One tumor was supplied by H at the seventh and by H + C at the
      eighth recurrence. As the number of local recurrences increased, the feeding
      vessel shifted from H to C. Especially, the right inferior phrenic artery (IPA)
      and renal capsular artery (RCA) supplied the tumor early, while the small right
      RCAs, adrenal arteries, and intercostal and lumbar artery supplied late
      recurrences in turns. In conclusion, HCCs located in the bare area are frequently
      supplied by extrahepatic vessels initially, while recurrence after
      chemoembolization is mainly due to extrahepatic blood supply. The right IPA and
      RCA are common feeding vessels demonstrated early, while other extrahepatic
      collateral supply from the retroperitoneal circulation occurs in turns during the
      later course.

PMID- 19756863
TI  - Biological remediation of groundwater containing both nitrate and atrazine.
AB  - Due to its high usage, mobility, and recalcitrant nature, atrazine is a common
      groundwater contaminant. Moreover, groundwaters that are contaminated with
      atrazine often contain nitrate as well. Nitrate interferes with the biological
      degradation of atrazine and makes it more difficult to use in situ biological
      methods to remediate atrazine contaminated groundwater. To solve this problem we
      used two reactors in sequence as models of in situ biobarriers; the first was a
      vegetable-oil-based denitrifying biobarrier and the second an aerobic reactor
      that oxygenated the denitrifying reactor's effluent. The reactors were inoculated
      with an atrazine-degrading microbial consortium and supplied with water
      containing 5 mg l(-1) nitrate-N and 3 mg l(-1) atrazine. Our hypothesis was that
      the denitrifying barrier would remove nitrate from the flowing water and that the
      downstream reaction would remove atrazine. Our hypothesis proved correct; the two
      reactor system removed 99.9% of the atrazine during the final 30 weeks of the
      study. The denitrifying barrier removed approximately 98% of the nitrate and
      approximately 30% of the atrazine while the aerobic reactor removed approximately
      70% of the initial atrazine. The system continued to work when the amount of
      nitrate-N in the influent water was increased to 50 mg l(-1). A mercury poisoning
      study blocked the degradation of atrazine indicating that biological processes
      were involved. An in situ denitrifying barrier coupled with an air injection
      system or other oxygenation process might be used to remove both nitrate and
      atrazine from contaminated groundwater or to protect groundwater from an atrazine
      spill.

PMID- 19756864
TI  - Use of mannitol inhalation challenge in assessment of cough.
AB  - Bronchial provocation testing uses a variety of direct and indirect inhalational
      challenges to evaluate airway hyperreactivity. Mannitol, a simple, easy-to
      administer hypertonic stimulus available in many countries, is currently under
      review by the FDA in the US. Healthy subjects show no airway response to inhaled
      mannitol; asthmatic patients respond with airway narrowing similar to challenges
      with hypertonic saline and exercise. Mannitol challenge also has a tussive effect
      that is independent of bronchoconstriction, suggesting different physiologic
      pathways. Patients with chronic cough show increased sensitivity to mannitol, and
      mannitol testing may be useful for evaluating heterogeneity in the cough
      response.

PMID- 19756865
TI  - Effect of pixel resolution on texture features of breast masses in mammograms.
AB  - The effect of pixel resolution on texture features computed using the gray-level
      co-occurrence matrix (GLCM) was analyzed in the task of discriminating
      mammographic breast lesions as benign masses or malignant tumors. Regions in
      mammograms related to 111 breast masses, including 65 benign masses and 46
      malignant tumors, were analyzed at pixel sizes of 50, 100, 200, 400, 600, 800,
      and 1,000 MUm. Classification experiments using each texture feature individually
      provided accuracy, in terms of the area under the receiver operating
      characteristics curve (AUC), of up to 0.72. Using the Bayesian classifier and the
      leave-one-out method, the AUC obtained was in the range 0.73 to 0.75 for the
      pixel resolutions of 200 to 800 MUm, with 14 GLCM-based texture features using
      adaptive ribbons of pixels around the boundaries of the masses. Texture features
      computed using the ribbons resulted in higher classification accuracy than the
      same features computed using the corresponding regions within the mass
      boundaries. The t test was applied to AUC values obtained using 100 repetitions
      of random splitting of the texture features from the ribbons of masses into the
      training and testing sets. The texture features computed with the pixel size of
      200 MUm provided the highest average AUC with statistically highly significant
      differences as compared to all of the other pixel sizes tested, except 100 MUm.

PMID- 19756866
TI  - Development and validation of automated 2D-3D bronchial airway matching to track
      changes in regional bronchial morphology using serial low-dose chest CT scans in
      children with chronic lung disease.
AB  - To address potential concern for cumulative radiation exposure with serial spiral
      chest computed tomography (CT) scans in children with chronic lung disease, we
      developed an approach to match bronchial airways on low-dose spiral and low-dose
      high-resolution CT (HRCT) chest images to allow serial comparisons. An automated
      algorithm matches the position and orientation of bronchial airways obtained from
      HRCT slices with those in the spiral CT scan. To validate this algorithm, we
      compared manual matching vs automatic matching of bronchial airways in three
      pediatric patients. The mean absolute percentage difference between the manually
      matched spiral CT airway and the index HRCT airways were 9.4 +/- 8.5% for the
      internal diameter measurements, 6.0 +/- 4.1% for the outer diameter measurements,
      and 10.1 +/- 9.3% for the wall thickness measurements. The mean absolute
      percentage difference between the automatically matched spiral CT airway
      measurements and index HRCT airway measurements were 9.2 +/- 8.6% for the inner
      diameter, 5.8 +/- 4.5% for the outer diameter, and 9.9 +/- 9.5% for the wall
      thickness. The overall difference between manual and automated methods was 2.1 +/
      1.2%, which was significantly less than the interuser variability of 5.1 +/-
      4.6% (p<0.05). Tests of equivalence had p<0.05, demonstrating no significant
      difference between the two methods. The time required for matching was
      significantly reduced in the automated method (p<0.01) and was as accurate as
      manual matching, allowing efficient comparison of airways obtained on low-dose
      spiral CT imaging with low-dose HRCT scans.

PMID- 19756867
TI  - Predicting early chemotherapy response with technetium-99m
      methoxyisobutylisonitrile SPECT/CT in advanced non-small cell lung cancer.
AB  - PURPOSE: The purpose of this study is to examine the prognostic value of
      prechemotherapy technetium-99m methoxyisobutylisonitrile ((99m)Tc-MIBI) uptake
      with single photon emission computed tomography/computed tomography (SPECT/CT) in
      relation to tumor size change measured by CT. METHODS: Eleven patients with stage
      IIIB/IV non-small cell lung cancer (NSCLC) underwent (99m)Tc-MIBI SPECT/CT within
      24 h before starting platinum-containing chemotherapy. Following the Response
      Evaluation Criteria in Solid Tumors guidelines, 20 lesions from the 11 patients
      were available for evaluation. Maximum (C (max)) and mean (C (mean)) MIBI counts
      were calculated for each lesion. One-dimensional (1D; longest diameter) and two
      dimensional (2D; area of the largest transverse surface) tumor measurements were
      assessed by two observers on the diagnostic CT and the response assessment CT
      after two cycles of chemotherapy. RESULTS: Bland-Altman analysis demonstrated no
      clinically significant bias between the observers. A solid correlation was found
      between (99m)Tc-MIBI C (mean) and change in the longest diameter (1D change) of
      the target lesion (rho = -0.62) using Spearman's rank correlation test. C (mean)
      also correlated negatively with change in the area of the largest transverse
      surface (2D change) of the target lesion (rho = -0.53). Furthermore, a
      correlation was established between (99m)Tc-MIBI C (max) and 1D change (rho = 
      0.56) in tumor size as well, though less strongly when compared to its C (mean)
      counterpart. CONCLUSIONS: Our series demonstrated solid, negative correlations
      between prechemotherapy (99m)Tc-MIBI uptake and tumor size change measured by CT
      for advanced NSCLC, particularly with C (mean) and 1D change.

PMID- 19756868
TI  - Deleterious effects of intermittent recombinant parathyroid hormone on cartilage
      formation in a rabbit microfracture model: a preliminary study.
AB  - Intermittent parathyroid hormone administration can enhance fracture healing in
      an animal model. Despite the success of exogenous parathyroid hormone on fracture
      healing and spine fusion, few studies have examined the role of parathyroid
      hormone on cartilage formation. We determined the effects of intermittent
      parathyroid hormone on cartilage formation in a rabbit microfracture model of
      cartilage regeneration. Twelve rabbits were divided into three equal groups: (1)
      microfracture alone, (2) microfracture + parathyroid hormone daily for 7 days,
      and (3) microfracture + parathyroid hormone for 28 days. Nonoperated
      contralateral knees were used as controls. The animals were sacrificed at 3
      months and gross and histologic analysis was performed. The microfracture alone
      group demonstrated the most healing on gross and histologic analysis. Treatment
      with either 1 or 4 weeks of parathyroid hormone inhibited cartilage formation.
      Although discouraging from a cartilage repair point of view, this study suggests
      that the role parathyroid hormone administration has in clinical fracture healing
      must be examined carefully. Although parathyroid hormone is beneficial to promote
      healing in spine fusion and midshaft fractures, its deleterious effects on
      cartilage formation suggests that it may have adverse effects on the outcomes of
      periarticular fractures such as tibial plateau injuries that require cartilage
      healing for a successful clinical outcome.

PMID- 19756869
TI  - Subungual exostosis of the finger with nail plate induction.

PMID- 19756870
TI  - Hand gangrene following unsuccessful cannulation of the internal jugular vein: a
      case report and literature review.
AB  - Hand gangrene following vascular cannula placement is uncommon and is usually the
      result of thrombotic occlusion of an artery. We describe a case of hand gangrene
      resulting in wrist disarticulation, following multiple unsuccessful attempts at
      internal jugular vein cannulation in a critically ill patient.

PMID- 19756871
TI  - Don't be 'mis-led': few herbal products have been implicated in lead poisoning.

PMID- 19756872
TI  - Do new drugs save lives?

PMID- 19756874
TI  - Limiting the influence of pharmaceutical industry gifts on physicians: self
      regulation or government intervention?
AB  - Concerns over the influence of pharmaceutical gifts on physicians have surged in
      recent years. This has prompted wide ranging legislative proposals in numerous
      states and in the federal government as well as stepped up efforts at self
      regulation by the pharmaceutical industry and the medical profession.
      Policymakers face the decision of whether to defer to self-regulation or support
      government intervention. This commentary describes efforts at self-regulation by
      the pharmaceutical industry and the medical profession. The author examines and
      critiques the wide ranging legislative strategies pursued to limit the influence
      of pharmaceutical gifts on physicians and concludes with suggestions for
      policymakers and the profession to limit influence and preserve public trust.

PMID- 19756875
TI  - Predictive and prognostic value of CA 19-9 in resected pancreatic adenocarcinoma.
AB  - BACKGROUND: Preoperative serum values of CA 19-9 have been reported to be
      associated with survival in patients undergoing resection of pancreatic
      adenocarcinoma. HYPOTHESIS: Preoperative CA 19-9 levels are associated with
      margin and/or lymph node status in patients undergoing pancreatoduodenectomy for
      pancreatic carcinoma. METHODS: We conducted a review of 143 patients undergoing
      pancreatoduodenectomy for pancreatic adenocarcinoma from July 2001 through April
      2006 at our institution. Preoperative serum values of CA 19-9 and total
      bilirubin, pathologic findings, and survival were analyzed. A cutoff value for CA
      19-9 (120 U/ml) was determined using a Cox proportional hazards model for
      survival. RESULTS: Overall survival at 1, 3, and 5 years for patients with CA 19
      9 < or = 120 U/ml was 76%, 41%, and 31%, respectively, versus 64%, 17%, and 10%
      for patients with CA 19-9 > 120 U/ml (p = 0.002). CA 19-9 > 120 U/ml was not
      associated, however, with a greater chance of an R1 or R2 resection (p = 0.86),
      tumor involving the SMA margin (p = 0.88), tumor at the portal vein groove (p =
      0.14), or lymph node metastases (p = 0.89). CONCLUSIONS: Our findings do not
      support a cutoff value for CA 19-9 that is associated with margin or lymph node
      involvement. Preoperative CA 19-9 < or = 120 U/ml is, however, associated with
      increased overall and recurrence-free survival.

PMID- 19756876
TI  - A standardized technique for laparoscopic rectal resection.
AB  - INTRODUCTION: Laparoscopic rectal resection (LRR) has not gained the same
      acceptance as laparoscopic segmental colonic resection because of technical
      challenges, increased operating time and costs, and concerns about the
      oncological outcome. DISCUSSION: One way to overcome these challenges is by
      standardizing the laparoscopic technique in the same way as has been done with
      the open rectal cancer surgery. We have established a standardized, stepwise
      laparoscopic procedure for rectal resections that enhances the transformation of
      laparoscopic skills, identifies indications for conversion early in the
      operation, and makes the operation predictable and reproducible for the whole
      surgical team. CONCLUSION: We believe this saves time in the operating room and
      builds up laparoscopic team expertise.

PMID- 19756877
TI  - Future applications of flexible endoscopy in esophageal surgery.
AB  - INTRODUCTION: Flexible endoscopy has long played a role in esophageal surgery,
      and procedures like perforation closure, stenting of occluding malignancies,
      antireflux procedures, and removal of Barretts are increasingly replacing open
      and laparoscopic procedures. We present early results of a series of acute animal
      experiments studying the feasibility of using flexible endoscopes for complex
      esophageal surgery such as Heller myotomy and esophagectomy. METHODS: A total of
      six animals and one human cadaver have been operated on in a series of three
      protocols. The first study involves extraluminal flexible endoscopy through a
      cervical incision. The esophagus is dissected to the phrenoesophageal junction
      and a Heller myotomy performed. The second study involves labeling specific
      mediastinal node areas using EUS and transesophageal tattooing. Transcervical
      access is once again obtained, and wide esophageal dissection is performed;
      sequential identification of the marked nodes is performed. The final study
      involves full thoracic esophageal mobilization and laparoscopic gastric
      mobilization for an esophagogastrectomy. RESULTS: Heller myotomy in five animals
      was performed via flexible endoscopy. Total operative time was 49 min with mean
      time for myotomy being 22 min. One animal had hemodynamic compromise from over
      insufflating the mediastinum with air. The second study involved three animals
      and one human cadaver. An average of four nodes was marked by EUS, and there was
      100% success in identifying all nodes with flexible medistinoscopy. Operative
      times had a mean of 187 min (147-227) for the animal model and 198 min for the
      cadaver model. CONCLUSION: There is a move to increase the role of flexible
      endoscopy in GI surgery. This is facilitated by the introduction of novel scopes
      and instrumentation designed for NOTES. We outline early favorable results from
      animal studies looking at the use of flexible endoscopy as a surgical tool for
      Heller myotomy and esophagectomy.

PMID- 19756878
TI  - Genetics in the pathogenesis of esophageal cancer: possible predictive and
      prognostic factors.
AB  - INTRODUCTION: Esophageal adenocarcinoma is the most rapidly increasing cancer in
      Western countries. Like esophageal squamous-cell carcinoma, these tumors are
      often detected at an advanced stage, requiring a multimodal concept. Despite
      improvements in detection, surgical resection, and (neo-) adjuvant therapy, the
      overall survival of esophageal cancer remains lower than other solid tumors. In
      fact, just 30-40% of the patients with advanced esophageal cancer benefit from a
      neoadjuvant therapy. Therefore, predictive/prognostic markers are needed to allow
      tailored multimodality therapy with increased efficacy. DISCUSSION: In recent
      years, there has been an exponential growth in our understanding of the cellular
      and molecular events associated with cell cycle regulation, programmed cell
      death, angiogenesis, and tumor growth. In this review, the classification of
      Hanahan and Weinberg is used concerning the six essential changes in
      carcinogenesis, i.e., the six hallmarks of cancer: (1) self-sufficiency in growth
      signals; (2) insensitivity to antigrowth signals; (3) avoidance of apoptosis; (4)
      limitless replicative potential; (5) sustained angiogenesis; and (6) tissue
      invasion and metastasis. CONCLUSIONS: According to these six steps, this review
      provides an update of the most recent data about predictive/prognostic molecular
      markers in patients with esophageal cancer.

PMID- 19756879
TI  - Non-acid gastroesophageal reflux measured using multichannel intraluminal
      impedance in older patients.
AB  - BACKGROUND: Diagnosing gastroesophageal reflux disease is challenging in the
      older population, as comorbid conditions can obscure the disease. METHODS: This
      prospective study included 97 participants: 25 healthy controls (group 1), 46
      reflux patients aged 26-64 (group 2), and 26 patients over 65 (group 3).
      Esophageal motility was assessed using conventional esophageal manometry, and 24
      h pH-metry and non-acid reflux episodes were assessed using multichannel
      intraluminal impedance. RESULTS: Among the older patients (group 3), 34% had
      reflux disease. The rate of lower esophageal sphincter insufficiency in group 3
      was comparable with that in group 2 and significantly different from group 1.
      Gastric 24-h pH-metry showed no significant differences between the groups.
      Esophageal pH-metry results for groups 1 and 3 differed significantly from those
      in group 2. Impedance assessment showed that older patients have non-acid reflux
      episodes in the recumbent position significantly more often in comparison with
      controls and reflux patients. Reflux patients and older patients had proximal
      reflux episodes significantly more often than healthy volunteers. CONCLUSIONS:
      Patients aged over 65 have non-acid reflux, particularly in the recumbent
      position, significantly more often than normal individuals and patients with
      reflux disease. Non-acid reflux may mimic a negative DeMeester score in older
      patients with severe reflux disease.

PMID- 19756880
TI  - Emerging concepts of bile reflux in the constellation of gastroesophageal reflux
      disease.
AB  - RATIONALE: Reflux of gastric and duodenal contents in patients with
      gastroesophageal reflux disease (GERD) has been postulated as a major cause of
      complications, such as Barrett's esophagus or malignant degeneration. FINDINGS:
      We present a summary of experimental, clinical, and immunohistochemical studies
      that show that acid and bile reflux are increased in patients who suffer from
      GERD, are the key factor in the pathogenesis of Barrett's esophagus, and are
      possibly related to the development of esophageal adenocarcinoma.

PMID- 19756881
TI  - Endoscopic and percutaneous preoperative biliary drainage in patients with
      suspected hilar cholangiocarcinoma.
AB  - INTRODUCTION: Controversy exists over the preferred technique of preoperative
      biliary drainage (PBD) in patients with hilar cholangiocarcinoma (HCCA) requiring
      major liver resection. The current study compared outcomes of endoscopic biliary
      drainage (EBD) and percutaneous transhepatic biliary drainage (PTBD) in patients
      with resectable HCCA. METHODS: One hundred fifteen consecutive patients were
      explored for HCCA between 2001 and July 2008 and assigned by initial PBD
      procedure to either EBD or PTBD. RESULTS: Of these patients, 101 (88%) underwent
      PBD; 90 patients underwent EBD as primary procedure, and 11 PTBD. The technical
      success rate of initial drainage was 81% in the EBD versus 100% in the PTBD group
      (P = 0.20). Stent dislocation was similar in the EBD and PTBD groups (23% vs.
      20%, P = 0.70). Infectious complications were significantly more common in the
      endoscopic group (48% vs. 9%, P < 0.05). Patients in the EBD group underwent more
      drainage procedures (2.8 vs. 1.4, P < 0.01) and had a significantly longer
      drainage period until laparotomy (mean 15 weeks vs. 11 weeks in the PTBD group; P
      < 0.05). In 30 patients, EBD was converted to PTBD due to failure of the
      endoscopic approach. CONCLUSIONS: Preoperative percutaneous drainage could
      outperform endoscopic stent placement in patients with resectable HCCA, showing
      fewer infectious complications, using less procedures.

PMID- 19756882
TI  - Surgical treatment and prognosis of esophageal cancer after distal gastrectomy.
AB  - BACKGROUND: The purpose of the present study was to explore the
      clinicopathological characteristics and operative therapeutic efficacy of
      thoracic esophageal cancer after gastrectomy and compare with those without
      gastrectomy. METHODS: From January 2000 to June 2007, 28 esophageal cancer
      patients with a history of distal gastrectomy underwent subtotal esophagectomy.
      Vascularized pedicle colonic conduit was most commonly used for esophageal
      substitution. Six hundred seventeen patients without a history of gastrectomy
      treated in the same period form the control group. After the operation,
      pathological characteristic, tumor staging, and survival statistics were
      analyzed. RESULTS: Of those patients with esophageal cancer associated with
      gastric remnant, the majority were male. There was an average of 16.5 years for
      diagnosing esophageal cancer from the initial partial gastrectomy, 75% (21/28) of
      them were patients with Billroth I anastomosis. The proportion of lower-third
      tumors in patients after gastrectomy (12 of 28 patients, 43%) was significantly
      higher compared with that of the patients with intact stomachs (124 of 617
      patients, 20%; P = 0.004). After surgical treatment, the overall 1-, 3-, and 5
      year survival rates of gastrectomized and nongastrectomized patients were 100%,
      35.00%, and 23.33% versus 98.93%, 59.42%, and 30.85% in stages I-II and 80.00%,
      30.00%, and 0% versus 98.59%, 62.03%, and 21.03% in stages III-IV. The log rank
      test of equality of survival distribution for the gastrectomized vs
      nongastrectomized patients was not significant in stages I-II (P = 0.5692) but
      was significant in stages III-IV (P = 0.0166). CONCLUSIONS: The patients with
      partial gastrectomy for more than 5 years, having upper gastrointestinal
      symptoms, should be considered having the risk of esophageal cancer associated
      with gastric remnant. For patients with a history of distal gastrectomy, a
      vascularized pedicle colonic conduit was most commonly used for esophageal
      substitution. Surgical efficacy was similar with the no-gastrectomy group in
      early stages I-II of esophageal cancer associated with gastric remnant but was
      lower compared with the no-gastrectomy group in stages III-IV. So, early
      diagnosis and an aggressive surgical approach may be crucial to achieve better
      outcomes for esophageal cancer patients with gastrectomy.

PMID- 19756883
TI  - Preoperative gastric acid secretion and the risk to develop Barrett's esophagus
      after esophagectomy for chagasic achalasia.
AB  - INTRODUCTION: The aim of this study was to determine the contribution of
      preoperative gastric secretory and hormonal response, to the appearance of
      Barrett's esophagus in the esophageal stump following subtotal esophagectomy.
      METHODS: Thirty-eight end-stage chagasic achalasia patients submitted to
      esophagectomy and cervical gastric pull-up were followed prospectively for a mean
      of 13.6 +/- 9.2 years. Gastric acid secretion, pepsinogen, and gastrin were
      measured preoperatively in 14 patients who have developed Barrett's esophagus
      (Group I), and the results were compared to 24 patients who did not develop
      Barrett's esophagus (Group II). RESULTS: In the group (I), the mean basal and
      stimulated preoperative gastric acid secretion was significantly higher than in
      the group II (basal: 1.52 vs. 1.01, p = 0.04; stimulated: 20.83 vs. 12.60, p =
      0.01). Basal and stimulated preoperative pepsinogen were also increased at the
      Group I compared to Group II (Basal = 139.3 vs. 101.7, p = 0.02; stimulated =
      186.0 vs. 156.5, p = 0.07. There was no difference in preoperative gastrin
      between the two groups. Gastritis was present during endoscopy in 57.1% of the
      Group I, while it was detected in 16.6% of the Group II, p = 0.014. CONCLUSIONS:
      Barrett's esophagus in the esophageal stump was associated to high preoperative
      levels of gastric acid secretion, serum pepsinogen, and also gastritis in the
      transposed stomach.

PMID- 19756884
TI  - CC chemokine receptor 9 enhances proliferation in pancreatic intraepithelial
      neoplasia and pancreatic cancer cells.
AB  - INTRODUCTION: Chemokine receptors may regulate the progression and metastasis of
      invasive malignancies. There are little data, however, regarding their role in
      premalignant lesions. Our objective was to determine the role of CC chemokine
      receptor 9 (CCR9) in pancreatic intraepithelial neoplasia (PanIN). METHODS: Human
      and murine formalin-fixed paraffin-embedded (FFPE) PanIN specimens were assessed
      for CCR9 expression. The established murine PanIN, invasive pancreatic cancer
      (5143PDA) and liver metastasis (5143LM) cell lines, and human pancreatic cancer
      cell line (PANC-1) were obtained to verify CCR9 expression and function. RESULTS:
      Immunohistochemistry of FFPE specimens demonstrated CCR9 expression in both
      murine and human PanIN lesions. CCR9 expression in murine and human cell lines
      was verified by Western blot assay, immunofluorescence, and flow cytometry. CCR9
      function was demonstrated by in vitro exposure to CCL25, the selective CCR9
      ligand, which resulted in significantly increased cell proliferation in PanIN and
      pancreatic cancer cell lines. CONCLUSIONS: This is the first report of chemokine
      receptor CCR9 expression in murine and human PanIN tissues. Our results
      demonstrate enhanced PanIN and pancreatic cancer cell proliferation with
      activation of CCR9 by its selective ligand CCL25. CCR9 may prove to be a novel
      therapeutic target for PanIN and its progression to invasive cancer.

PMID- 19756885
TI  - Variable optimization for the formation of three-dimensional self-organized heart
      muscle.
AB  - Cardiac tissue-engineering research is focused on the development of functional
      three-dimensional (3D) heart muscle in vitro. These models allow the detailed
      study of critical events in organogenesis, such as the establishment of cell-cell
      communication and construction and modification of the extracellular matrix. We
      have previously described a model for 3D heart muscle, termed cardioids, formed
      by the spontaneous delamination of a cohesive monolayer of primary cells in the
      absence of any synthetic scaffolding material. In an earlier publication, we have
      shown that, upon electrical stimulation, cardioids generate a twitch force in the
      range of 200-300 microN, generate a specific force (twitch force normalized to
      total cross-sectional area) of 2-4 kN/m(2), and can be electrically paced at
      frequencies of up to 10 Hz without any notable fatigue. We have two objectives
      for the current study: model development and model optimization. Our model
      development efforts are focused on providing additional characterization of the
      cardioid model. In this study, we show for the first time that cardioids show a
      pattern of gene expression comparable to that of cells cultured in two dimensions
      on tissue culture plastic and normal mammalian heart muscle. Compared with
      primary cardiac cells cultured on tissue culture plastic, the expression of alpha
      myosin heavy chain (MHC), beta-MHC, SERCA2, and phospholamban was significantly
      higher in cardioids. Our second objective, model optimization, is focused on
      evaluating the effect of several cell culture variables on cardioid formation and
      function. Specifically, we looked at the effect of plating density (1.0-4.0 x
      10(6) cells per cardioid), concentration of two adhesion proteins (laminin at 0.2
      2.0 microg/cm(2) and fibronectin at 1-10 microg/cm(2)), myocyte purity (using
      preplating times of 15 and 60 min), and ascorbic acid stimulation (1-100
      microl/ml). For our optimization studies, we utilized twitch force in response to
      electrical stimulation as our endpoint metric. Based on these studies, we found
      that cardioids formed with a plating density in the range 3-4 x 10(6) cells per
      cardioid generated the maximum twitch force, whereas increasing the surface
      adhesion protein (using either laminin or fibronectin) and increasing the myocyte
      purity both resulted in a decrease in twitch force. In addition, increasing the
      ascorbic acid concentration resulted in an increase in the baseline force of
      cardioids, which was recorded in the absence of electrical stimulation. Based on
      the model development studies, we have shown that cardioids do indeed exhibit a
      gene expression pattern similar to normal mammalian heart muscle. This provides
      further validity for the cardioid model. Based on the model optimization studies,
      we have identified specific cell culture regimes which support cardioid formation
      and function. These results are specific to the cardioid model; however, they may
      be translated and applied to other tissue-engineering models. Collectively, the
      work described in this study provides insight into the formation of functional 3D
      heart muscle and the effect of several cell culture variables on tissue formation
      and function.

PMID- 19756886
TI  - Case reports--resolution of Barrett's disease and esophageal epithelial atypia
      after gastric bypass and LAP-BAND.
AB  - Gastroesophageal reflux is a well-recognized complication of obesity. Long-term
      reflux is associated with the progression from esophageal injury to Barrett's
      esophagus then to carcinoma. Bariatric surgery may prevent reflux and the
      progression of esophageal injury. We present two cases that had remission of
      their esophageal problems after differing bariatric operations.

PMID- 19756887
TI  - Clinical utility of endoscopy and barium swallow X-ray in the diagnosis of
      sliding hiatal hernia in morbidly obese patients: a study before and after
      gastric bypass.
AB  - BACKGROUND: The main clinical consequence of sliding hiatal hernia (SHH) is
      gastroesophageal reflux disease (GERD). Endoscopy and barium swallow X-ray are
      commonly used to diagnose SHH. We aimed to assess the clinical utility of
      endoscopy and X-ray in the diagnosis of SHH in morbidly obese patients before and
      after gastric bypass (GBP). METHODS: Ninety-two patients underwent reflux
      symptoms evaluation, upper gastrointestinal endoscopy, and barium swallow X-ray
      before and 6 months after banded GBP. The performance of endoscopy in diagnosing
      SHH was assessed, taking X-ray as reference. Endoscopy and X-ray were tested as
      predictors of SHH with GERD. RESULTS: SHH was more prevalent when characterized
      by X-ray than endoscopy either before (33% vs. 17%; P = 0.017) or after GBP (26%
      vs. 7%; P = 0.001). Endoscopy showed low sensitivity (<or=40%) and high
      specificity (>or=94%) in diagnosing SHH. Before GBP, more patients with SHH had
      GERD compared to patients without SHH using either X-ray (83% vs. 58%; P = 0.016)
      or endoscopy (94% vs. 61%; P = 0.009). After GBP, only patients with radiologic
      evidence of SHH showed higher prevalence of GERD compared to patients without SHH
      (50% vs. 26%; P = 0.037). SHH patients also reported weekly or daily vomit more
      often than patients without SHH (59% vs. 32%; P = 0.026). CONCLUSIONS: In
      morbidly obese patients, X-ray is superior to endoscopy in diagnosing SHH either
      before or after banded GBP. In patients treated with this technique, the
      utilization of X-ray may help in the management of reflux symptoms and frequent
      vomit.

PMID- 19756888
TI  - Is obesity a contraindication for minimal invasive total knee replacement? A
      prospective randomized control trial.
AB  - BACKGROUND: Although total knee replacement (TKR) has been proven a very
      successful treatment modality for the end-stage knee osteoarthritis (OA) in obese
      patients, the rehabilitation period often is long and painful. Minimal invasive
      surgery (MIS) has gained much attention in TKR promising fast and less painful
      recovery. However, little is known about the effectiveness of the technique in
      the obese adult population. METHODS: One hundred consecutive patients with body
      mass index (BMI) > 30 kg/m(2) and tricompartmental knee OA were randomly assigned
      to undergo either standard TKR (50 patients) or MIS-TKR (50 patients). The
      patients were assessed clinically and radiologically before the procedure and at
      subsequent postoperative follow-up visits, until 2 years after the operation.
      RESULTS: Knee society function and pain scores were significantly higher in MIS
      group for 3 months following surgery. Patients after MIS had also lower levels of
      pain during hospitalization. Tourniquet time was on average 7 min longer during
      MIS-TKR (p = 0.03) but operative time was almost equal in both groups (p = 0.11).
      No statistical significant difference was found between groups regarding the
      amount of blood loss (p = 0.49) or incidence of allogeneic blood transfusion (p =
      0.27). Active straight leg raising was achieved 2.2 days earlier, on average,
      after MIS-TKR (p < 0.001). No severe complications or residual coronal and
      sagittal imbalance were identified. Component alignment was in normal limits and
      similar in both groups. In MIS group, higher BMI did not have a negative
      predictive effect on knee pain and function. CONCLUSIONS: MIS is a reliable and
      safe option in obese patients undergoing TKR regardless the level of BMI. It is
      associated with improved early clinical outcome without sacrificing radiographic
      positioning of the implants.

PMID- 19756889
TI  - A surgical rat model of sleeve gastrectomy with staple technique: long-term
      weight loss results.
AB  - BACKGROUND: Sleeve gastrectomy (SG) is one of the surgical procedures applied for
      treating morbid obesity consisting of removing the gastric fundus and
      transforming the stomach into a narrow gastric tube. The aim of this experimental
      study is to create a functional model of SG and to present the long-term weight
      loss results. METHODS: Twenty adult Wistar rats were fed with high fat diet for
      12 weeks before being divided randomly in two groups of ten rats each. One group
      underwent SG performed with the use of staples, and the other group underwent a
      sham operation (control group). The animals' weight was evaluated weekly for 15
      weeks after the operation. RESULTS: All animals survived throughout the
      experiment. After the operation both groups started to lose weight with maximum
      weight loss on the seventh postoperative day (POD) for the sham-operated group
      and on the 15th POD for the SG group. Thereafter, both groups started to regain
      weight but with different rates. By the fourth postoperative week (POW), the
      average weight of the sham group did not differ statistically significantly
      compared to the preoperative weight, while after the eighth POW, rats' average
      weight was statistically significantly increased compared to the preoperative
      value. On the other hand, average weight of the SG group was lower
      postoperatively until the end of the study compared to the preoperative average
      weight. CONCLUSION: We have created a surgical rat model of experimental SG
      model, enabling the further study of biochemical and hormonal parameters.

PMID- 19756890
TI  - The impact of various anthropometric measurements of obesity on pulmonary
      function in candidates for surgery.
AB  - BACKGROUND: Obesity has proven to be associated with respiratory symptoms and
      impaired pulmonary function, which could increase the incidence of postoperative
      complications after bariatric surgery. However, the component of obesity that has
      the most influence on pulmonary function has not been identified, especially in
      Asian-Pacific populations. METHODS: This cross-sectional study enrolled obese
      Chinese patients >or=18 years of age with a body mass index (BMI) >32 kg/m(2),
      who were being evaluated for bariatric surgery. All patients performed pulmonary
      function test, and the results were analyzed according to various anthropometric
      measurements. Multiple-regression analyses were also conducted and adjusted for
      age, sex, and smoking history to determine the factors that impaired the
      pulmonary function of the obese patients. RESULTS: A total of 150 consecutive
      patients were enrolled from July 2007 to August 2008. We found that body weight,
      BMI, waist circumference (WC), hip circumference, and waist-to-height ratio but
      not waist-to-hip ratio had a significant correlation with decreased forced vital
      capacity (FVC), forced expiratory volume in the first second (FEV1), total lung
      capacity (TLC), vital capacity (VC), and increased diffusing capacity of the lung
      for carbon monoxide to alveolar gas volume. After multiple linear regression
      analysis, only WC was associated with reductions in FEV1, FVC, TLC, and VC.
      CONCLUSIONS: Obesity is associated with a restrictive pattern of impaired
      pulmonary function in various anthropometric parameters measured in obese Chinese
      adults in Taiwan. Among these parameters, WC had the greatest impact on pulmonary
      function, which could also implicate the rate of postoperative complication and
      the need of more intensive care after bariatric surgery.

PMID- 19756891
TI  - Safe limits for aspirate volume under wet liposuction.
AB  - BACKGROUND: Hypovolemia is a hemodynamic disorder occasionally associated with
      liposuction. The purpose of this study is to settle a safe limit for the volume
      of aspirate under wet liposuction relating this volume to body weight. The
      criteria used to establish this limit were based on the Advanced Trauma Life
      Support (ATLS). METHODS: Thirty patients underwent wet liposuction and were
      submitted postoperatively to a 24-h noninvasive monitoring control of vital
      signs. Tachycardia (over 100 bpm) and systolic hypotension (below 100 mmHg) were
      recorded as well as urinary volume and respiratory rate. Hemoglobin, hematocrit,
      and leukocyte counts were determined preoperatively and also determined 1 and 6 h
      postoperatively. RESULTS: The volume of aspirate ranged from 1,480 to 3,980 ml
      (2.6% to 6.9% of body weight). Hemoglobin count decreased around 6 h
      postoperatively compared to the immediate preoperative period (p<0.0001). An
      increase of leukocytes was observed around 6 h postoperatively when compared with
      the preoperative period-nearly 30 min before surgery (p<0.0001). No association
      was found between hemoglobin or leukocyte counts and volume of aspirate. In 15
      patients, tachycardia and/or hypotension were recorded postoperatively. These
      hemodynamic disorders were associated to volumes of aspirate higher than 5% of
      body weight. CONCLUSIONS: Under wet liposuction, a volume of aspiration not
      superior to 5% of body weight is proposed as a safe limit. It has been found as a
      clue to avoid hypovolemia and subsequently the shock. This statement is in
      agreement with ATLS guidelines.

PMID- 19756892
TI  - Radiological findings in symptomatic internal hernias after laparoscopic gastric
      bypass.
AB  - BACKGROUND: Internal hernias (IHs) can complicate laparoscopic Roux-en-Y gastric
      bypass (LRYGB). A number of radiological investigations can be used in the
      diagnosis. These include plain X-rays, upper gastrointestinal (UGI) series,
      ultrasound, and computed tomography (CT) scanning. We present radiological
      findings in our series of 58 symptomatic internal hernias based on our 6-year
      experience (2000-2006) of 2,572 LRYGB patients. METHODS: A retrospective chart
      review was performed of all patients undergoing LRYGB who developed symptomatic
      internal hernia requiring operative intervention between January 1, 2000 and
      September 15, 2006. Types of radiological tests performed and their results were
      recorded. RESULTS: Fifty-eight symptomatic internal hernias were recorded, of
      which 56/58 (97%) underwent radiological investigation; 2/58 went directly to
      surgery. Of the 56 patients who underwent diagnostic imaging, 41 plain abdominal
      X-rays, 37 CT scans, 26 UGI series, and eight ultrasound scans were performed.
      Sixty-five percent of UGI series and 92% of CT scans had positive features
      diagnostic of internal hernia. Performing both CT and UGI series successfully
      diagnosed IH in 100% of cases. Subgroup analysis did not reveal any association
      between positive result of imaging test and type of internal hernia. CONCLUSION:
      CT scanning is the single most effective radiological investigation for
      diagnosing internal hernias post-LRYGB. In non-diagnostic cases, the addition of
      an upper GI series increases the diagnostic rate to 100%.

PMID- 19756893
TI  - Apelin levels are increased in morbidly obese subjects with type 2 diabetes
      mellitus.
AB  - BACKGROUND: The physiological role of apelin in obesity and diabetes remains
      unclear. Although apelin has been studied in persons with different conditions,
      no studies have yet examined the joint influence of obesity and diabetes on
      apelin levels. We measured the changes in apelin levels in morbidly obese
      subjects, with and without diabetes, and in the inverse situation of improvement
      in carbohydrate metabolism as a result of bariatric surgery. METHODS: The study
      was undertaken in 54 morbidly obese persons, 16 of whom had type 2 diabetes
      mellitus, before and 7 months after undergoing bariatric surgery, and in 12
      healthy, nonobese persons. Measurements were made of apelin levels and insulin
      sensitivity by an intravenous glucose tolerance test. RESULTS: The apelin levels
      in the morbidly obese patients prior to surgery were significantly higher than
      those of the controls only when the morbidly obese subjects were diabetic (P <
      0.005). Apelin levels correlated significantly in the morbidly obese patients
      with serum triglycerides (r = 0.292, P = 0.032) and glucose (r = 0.337, P =
      0.039). Bariatric surgery resulted in a significant decrease in apelin levels
      only in the morbidly obese subjects with impaired fasting glucose or diabetes.
      The change in apelin levels correlated significantly in the morbidly obese
      patients with the changes in serum glucose (r = 0.338, P = 0.038) and insulin
      sensitivity (r = -0.417, P = 0.043). CONCLUSIONS: This study demonstrates that
      obesity is not the main determinant of the rise in apelin levels. The association
      between apelin levels and glucose concentrations and insulin sensitivity provides
      evidence that apelin may play a role in the pathogenesis of diabetes.

PMID- 19756894
TI  - Laparoscopic gastric banding as revisional procedure to failed vertical
      gastroplasty.
AB  - BACKGROUND: Vertical gastroplasty (VG) was worldwide and until recently a very
      popular restrictive bariatric procedure. Unfortunately, many patients required
      revisional surgery for failure of this technique. The present study aimed to
      evaluate retrospectively the feasibility, safety, and efficiency of conversion of
      failed VGs to laparoscopic adjustable gastric banding (LAGB). METHODS: Forty
      patients underwent LAGB as revisional surgery between August 2001 and June 2008.
      Preceding VGs were performed either by open procedure {silastic ring vertical
      gastroplasty (SRVG, n = 21) and vertical-banded gastroplasty (VBG, n = 10)} or by
      laparoscopy {laparoscopic silastic ring vertical gastroplasty (L-SRVG, n = 9)}.
      The delay between initial and revisional surgery was significantly shorter for
      SRVG (5.5 +/- 1.7 years; p < 0.001) as compared to VBG and L-SRVG (9.2 +/- 2.3
      and 9.4 +/- 1.8 years, respectively). The reasons for failure of the VG were:
      disruption of the staple line (n = 23), excessive enlargement of the gastric
      pouch (n = 15) and inefficient stoma (n = 2). Patients were qualified for
      revisional surgery in case of uncontrolled weight regain with or without frequent
      vomiting. RESULTS: There were three conversions from laparoscopy to laparotomy
      (7.5%). There was no mortality. Minor morbidity was 12.5%. There were two major
      complications (5%); one incarcerated port-site hernia requiring small bowel
      resection, and one band erosion necessitating band removal. The mean BMI dropped
      from 38.9 kg/m(2) before revision to 30.7 kg/m(2) after conversion to LAGB
      (follow-up 6-88 months). CONCLUSIONS: Conversion of failed VGs to gastric banding
      is safe and efficient. The morbidity rate is acceptable. Gastric banding to
      correct failing VG is a reasonable option when performed in selected patients.

PMID- 19756895
TI  - The use of an improved intragastric balloon technique to reduce weight in pre
      obese patients--preliminary results.
AB  - BACKGROUND: In this study, a new safer and faster intragastric balloon procedure
      was also employed to treat pre-obese patients (body mass index (BMI) < 30).
      METHODS: From June 2006 to June 2009, 20 such patients were submitted to the
      Silimed Gastric Balloon treatment, as a part of a multidisciplinary program
      involving clinical, psychological, and behavioral approaches. For the 16 patients
      who had completed the 5-6-month treatment, the initial mean weight and mean BMI
      were 74 kg and 27.5 kg/m(2), respectively. RESULTS: After the treatment, the mean
      weight and BMI values decreased significantly to 65.9 kg and 24.5 kg/m(2),
      respectively. There were only minor complications--nausea and vomiting--with the
      exception of two cases of spontaneous deflation of the devices which were
      successfully removed by gastric endoscopy. CONCLUSIONS: Thus, preliminary data
      suggest that this new intragastric balloon procedure might also be a safe and
      effective treatment for weight loss in pre-obese patients.

PMID- 19756896
TI  - Cost-effectiveness and budget impact of obesity surgery in patients with type 2
      diabetes in three European countries(II).
AB  - BACKGROUND: This study aimed to establish a payer-perspective cost-effectiveness
      and budget impact model of adjustable gastric banding (AGB) and gastric bypass
      (GBP) vs. conventional treatment (CT) in patients with a body mass index (BMI) >
      or = 35 kg x m(-2) and type 2 diabetes mellitus (T2DM) in Austria, Italy, and
      Spain. METHODS: A health economics model described in a previous publication was
      applied to resource utilization and cost data in AGB, GBP, and CT from Austria,
      Italy, and Spain in 2009. RESULTS: The base case time scope is 5 years; the
      annual discount rate for utilities and costs is 3.5%. In Austria and Italy, both
      AGB and GBP are cost-saving and are thus dominant in terms of incremental cost
      effectiveness ratio compared to CT. In Spain, AGB and GBP yield a moderate cost
      increase but are cost-effective, assuming a willingness-to-pay threshold of
      30,000 euro per quality adjusted life-year. Under worst-case analysis, AGB and
      GBP remain cost-saving or around breakeven in Austria and Italy and remain cost
      effective in Spain. CONCLUSION: In patients with T2DM and BMI > or = 35 kg x m(
      2) at 5-year follow-up vs. CT, AGB and GBP are not only clinically effective and
      safe but represent satisfactory value for money from a payer perspective in
      Austria, Italy, and Spain.

PMID- 19756898
TI  - The ways of 'being' and 'becoming' human.
AB  - We argue that developing integrative models of psychological phenomenon require
      dealing simultaneously with information-theoretic and meaning making processes at
      the individual and group levels. Attempts to fuse these across levels based on
      intentionality become difficult because phenomena at the lower level organisms
      are conceptualized employing concrete systems language, while in case of human
      and social systems both concrete and abstracted systems concepts are used.
      Intentionality also needs to be looked at as arising out of the processes of both
      being and becoming. Fusing of psycho-and socio-logics necessarily requires taking
      into consideration psychological processes and notions of intentionality and
      future within cultural contexts in a more holistic manner. It is also argued that
      both at personal and collective levels, human intentionality operate as bounded
      intentionality alternating between states of being and becoming.

PMID- 19756899
TI  - Why dichotomies can be misleading while dualities fit the analysis of complex
      phenomena.
AB  - Humans' tendency to classify and categorize is definitely overspread, but it can
      be misleading at all fields, including epistemology, ontology, theory, and
      analysis of scientific knowledge construction itself. Sanchez and Loredo (IPBS:
      Integrative Psychological & Behavioral Science 43:4, 2009-DOI 10.1007/s12124-009
      9091-1) in their article on classification of contemporary constructivists fall
      exactly into such pitfall- even as their effort to make sense of many outstanding
      theorists is impressive and inriguing. A further analysis, however, points at the
      theoretical trap posed by such endeavor, for models arisen from different
      epistemological standpoints cannot be compared along the lines of a simplistic
      polarity between "objectivism" and "subjectivism". There is much more to be taken
      into account when a intrinsically complex subject like constructivism and
      constructionism epistemological approach and their welcome different versions-
      perspectives--are submitted to analysis and critical evaluation.

PMID- 19756900
TI  - Case report: reconstruction of the distal tibia with porous tantalum spacer after
      resection for giant cell tumor.
AB  - Treatment options for giant cell tumors of the distal tibia include curettage and
      cement packing, curettage and bone grafting, or resection and reconstruction for
      aggressive tumors. Curettage of aggressive tumors often leads to severe bone loss
      requiring reconstruction. Allograft and autograft may be effective options for
      reconstruction, but each is associated with drawbacks including the possibility
      of infection and collapse. We present a case of giant cell tumor of the distal
      tibia treated with curettage and arthrodesis using a porous tantalum spacer.
      Complete removal of the tumor and successful arthrodesis of the ankle were
      accomplished using the spacer. The patient returned to pain-free walking along
      with eradication of the giant cell tumor. We believe porous tantalum spacers are
      a reasonable option for reconstructing the distal tibia after curettage of a
      giant cell tumor with extensive bone loss.

PMID- 19756901
TI  - A new incision technique to reduce tibiofemoral mismatch in rotationplasty.
AB  - Rotationplasty provides stable and durable biologic reconstruction after tumor
      resection around the knee and renders reliable results, in young patients.
      However, after resection of the tumor, there is often a mismatch between the
      circumference of the proximal (femoral) and the distal (tibial) parts. Because
      rotationplasty includes an intercalary amputation where the ends are readapted,
      there is always a mismatch of the proximal and distal circumferences of the soft
      tissue envelope. To facilitate skin closure without tension and to avoid impaired
      wound healing and subsequent infections, the type of incision is critical and
      must be carefully planned. We present a new incision technique for rotationplasty
      about the knee. Half of the difference of the incision length of the proximal and
      distal circumferences represents the base of the triangle proximally, medially
      and laterally of the thigh. After adapting both ends, the peak of this flat
      triangle is distally adapted via a vertical incision which allows it to match
      unequal circumferences. This technique was used in eight patients, in all of whom
      the wounds healed uneventfully.

PMID- 19756902
TI  - Capacitively coupled electric field for pain relief in patients with vertebral
      fractures and chronic pain.
AB  - Fragility vertebral fractures often are associated with chronic back pain
      controlled by analgesic compounds. Capacitive coupling electrical stimulation is
      a type of electrical stimulation technology approved by the US FDA to
      noninvasively enhance fracture repair and spinal fusion. These uses suggest it
      would be a possible treatment for patients with back pain attributable to
      vertebral fractures. We therefore randomized 51 postmenopausal women with
      multiple fractures and chronic pain to the use of one of two indistinguishable
      devices delivering either the standard capacitive coupling electrical stimulation
      by Osteospine (active group) or low intensity pulse (control group). Twenty
      patients of the active group and 21 of the control group (80%) completed the
      study for a total duration of 3 months. The mean visual analog scale values for
      pain and the Quality of Life Questionnaire of the European Foundation for
      Osteoporosis (QUALEFFO) scores improved in both groups. We observed a
      relationship between hours of treatments and reductions in pain intensity only in
      the active group. Capacitive coupling electrical stimulation was not more
      effective than control treatment when comparing mean visual analog scale pain and
      QALEFFO scores in the two groups and when adjusting for the hours of treatment.
      However, the proportion of patients able to discontinue NSAIDs owing to
      elimination or reduction of pain was greater in the active group than in the
      control group. We interpret these findings as suggesting capacitive coupling
      electrical stimulation controls pain in some patients and reduces the use of
      NSAIDs. LEVEL OF EVIDENCE: Level I, therapeutic study. See Guidelines for Authors
      for a complete description of levels of evidence.

PMID- 19756903
TI  - Correlation of computed tomography with histology in the assessment of
      periprosthetic defect healing.
AB  - Computed tomography (CT) may more accurately assess the healing of grafted
      osteolytic lesions around acetabular components compared with plain radiographs,
      although clinical validation is lacking. To determine whether clinical or micro
      CT imaging could assess accurately the grafted lesion compared with histology, we
      therefore quantified bone healing and ingrowth to determine an effective rhBMP-2
      dose and ratio to allograft bone when grafted adjacent to a cementless porous
      coated component. We grafted surgically created acetabular defects in canines (n
      = 20) before uncemented total hip arthroplasty. At 6 weeks, embedded acetabula
      were imaged and the CT slice images matched to histology section images. The
      percentage of bone in the defect and growth into the porous surface was assessed
      quantitatively. Low-dose rhBMP-2 with allograft (1:5 ratio) resulted in a higher
      percentage of defect healing (43.8%) than rhBMP-2 alone (29.2%) and a higher
      percentage of bone ingrowth (15.7%) than allograft bone alone (1.1%) as measured
      by histology. Micro-CT measurements were similar to histologic measurements of
      defect healing, whereas clinical CT overestimated periprosthetic bone by 38%.
      Neither clinical CT nor micro-CT techniques are adequate for assessing ingrowth
      or the bone-implant interface with metal artifacts.

PMID- 19756905
TI  - The parathyroid hormone and bone. Franklin C. McLean, MD CORR 1957;9:46-60.

PMID- 19756904
TI  - Diagnosing suspected scaphoid fractures: a systematic review and meta-analysis.
AB  - Imaging protocols for suspected scaphoid fractures among investigators and
      hospitals are markedly inconsistent. We performed a systematic review and meta
      analysis to assess and compare the diagnostic performance of bone scintigraphy,
      MRI, and CT for diagnosing suspected scaphoid fractures. Twenty-six studies were
      included. Sensitivity, specificity, and diagnostic odds ratio were pooled
      separately and summary receiver operating characteristic curves were fitted for
      each modality. Meta-regression analyses were performed to compare these
      modalities. We obtained likelihood ratios derived from the pooled sensitivity and
      specificity and, using Bayes' theorem, calculated the posttest probability by
      application of the tests. The pooled sensitivity, specificity, natural logarithm
      of the diagnostic odds ratio, and the positive and negative likelihood ratios
      were, respectively, 97%, 89%, 4.78, 8.82, and 0.03 for bone scintigraphy; 96%,
      99%, 6.60, 96, and 0.04 for MRI; and 93%, 99%, 6.11, 93, and 0.07 for CT. Bone
      scintigraphy and MRI have equally high sensitivity and high diagnostic value for
      excluding scaphoid fracture; however, MRI is more specific and better for
      confirming scaphoid fracture. We believe additional studies are needed to assess
      diagnostic performance of CT, especially paired design studies or randomized
      controlled trials to compare CT with MRI or bone scintigraphy. LEVEL OF EVIDENCE:
      Level III, diagnostic study. See the Guidelines for Authors for a complete
      description of levels of evidence.

PMID- 19756906
TI  - Hip resurfacing results for osteonecrosis are as good as for other etiologies at
      2 to 12 years.
AB  - A bone-conserving prosthetic solution, such as hip resurfacing arthroplasty, is
      desirable for patients with osteonecrosis (ON) of the femoral head because of
      their young age. However, many surgeons are reluctant to perform hip resurfacing
      for ON because of large femoral head defects. To ascertain whether this
      reluctance is warranted, we determined the mid- to long-term effects of ON on the
      survivorship, radiographic implant fixation, and disease-specific and quality-of
      life scores of hip resurfacing. We compared the results of metal-on-metal
      resurfacing performed for ON of the hip (including large lesions) with those of
      resurfacing performed for other causes. The ON group had 70 patients (85 hips)
      and the control group 768 patients (915 hips) including all other etiologies
      operated on during the same period. The ON group was younger and had a greater
      incidence of femoral defects, a smaller component size, and a lower body mass
      index, three variables previously shown to reduce survivorship in hip
      resurfacing. We observed no difference in survivorship between the ON group and
      the control group even after adjusting for head size, body mass index, and defect
      size. Pain relief, walking, and function scores were comparable postoperatively.
      The activity level was lower in the ON group. Our data suggest ON is not a
      contraindication for resurfacing even with large femoral head defects. LEVEL OF
      EVIDENCE: Level III, therapeutic study. See Guidelines for Authors for a complete
      description of levels of evidence.

PMID- 19756907
TI  - The Otto Aufranc Award: Identification of a 4 Mb region on chromosome 17q21
      linked to developmental dysplasia of the hip in one 18-member, multigeneration
      family.
AB  - Developmental dysplasia of the hip (DDH) is a disabling condition that, depending
      on geography, can afflict between 20% and 80% of patients with end-stage
      arthritis of the hip. Despite its prevalence, the etiology of this disease
      remains unknown. DDH is a complex disorder with both environmental and genetic
      causes. Based on the literature the candidate genes for the disease are HOXB9,
      collagen type I alpha1, and DLX 3. The purpose of our study was to map and
      characterize the gene or genes responsible for this disorder by family linkage
      analysis. We recruited one 18-member, multigeneration affected family to provide
      cheek swabs and blood samples for isolation of DNA. Amplified DNA underwent a
      total genome scan using GeneChip Mapping 250 K Assay (Affymetrix, Santa Clara,
      CA). We observed only one region with a LOD score greater than 1.5: a 4 Mb region
      on chromosome 17q21.32, yielding a LOD score of 1.82. While a LOD score of 1.82
      does not meet the accepted standard for linkage we interpret these data as
      suggesting the responsible gene could be linked to this region, which includes a
      cluster of homeobox genes (HOX genes) that are part of the developmental
      regulatory system providing cells with specific positional identities along the
      developing joint and spine. Discovering the genetic basis of the disease would be
      an important step in understanding the etiology of this disabling condition.

PMID- 19756908
TI  - Physician collective bargaining.
AB  - Current antitrust enforcement policy unduly restricts physician collaboration,
      especially among small physician practices. Among other matters, current
      enforcement policy has hindered the ability of physicians to implement efficient
      healthcare delivery innovations, such as the acquisition and implementation of
      health information technology (HIT). Furthermore, the Federal Trade Commission
      and Department of Justice have unevenly enforced the antitrust laws, thereby
      fostering an increasingly severe imbalance in the healthcare market in which
      dominant health insurers enjoy the benefit of largely unfettered consolidation at
      the cost of both consumers and providers. This article traces the history of
      antitrust enforcement in healthcare, describe the current marketplace, and
      suggest the problems that must be addressed to restore balance to the healthcare
      market and help to ensure an innovative and efficient healthcare system capable
      of meeting the demands of the 21st century. Specifically, the writer explains how
      innovative physician collaborations have been improperly stifled by the policies
      of the federal antitrust enforcement agencies, and recommend that these policies
      be relaxed to permit physicians more latitude to bargain collectively with health
      insurers in conjunction with procompetitive clinical integration efforts. The
      article also explains how the unbridled consolidation of the health insurance
      industry has resulted in higher premiums to consumers and lower compensation to
      physicians, and recommends that further consolidation be prohibited. Finally, the
      writer discusses how health insurers with market power are improperly undermining
      the physician-patient relationship, and recommend federal antitrust enforcement
      agencies take appropriate steps to protect patients and their physicians from
      this anticompetitive conduct. The article also suggests such steps will require
      changes in three areas: (1) health insurers must be prohibited from engaging in
      anticompetitive activity; (2) the continuing improper consolidation of the health
      insurance industry must be curtailed; and (3) the physician community must be
      permitted to undertake the collaborative activity necessary for the establishment
      of a transparent, coordinated, and efficient delivery system.

PMID- 19756909
TI  - Recent advances in cardiac PET and PET/CT myocardial perfusion imaging.

PMID- 19756910
TI  - Who gets the heart attack: noninvasive imaging markers of plaque instability.

PMID- 19756912
TI  - Dynamic Monitoring of Cellular Remodeling Induced by the Transforming Growth
      Factor-beta1.
AB  - The plasticity of differentiated adult cells could have a great therapeutic
      potential, but at the same time, it is characteristic of progression of serious
      pathological states such as cancer and fibrosis. In this study, we report on the
      application of a real-time noninvasive system for dynamic monitoring of cellular
      plasticity. Analysis of the cell impedance profile recorded as cell index using a
      real-time cell analyzer revealed its significant increase after the treatment of
      prostate epithelial cells with the transforming growth factor-beta1. Changes in
      the cell index profile were paralleled with cytoskeleton rebuilding and induction
      of epithelial-mesenchymal transition and negatively correlated with cell
      proliferation. This novel application of such approach demonstrated a great
      potential of the impedance-based system for noninvasive and real-time monitoring
      of cellular fate.

PMID- 19756911
TI  - Are neuropathological conditions relevant to ethylmercury exposure?
AB  - Mercury and mercurial compounds are among the environmentally ubiquitous
      substances most toxic to both wildlife and humans. Once released into the
      environment from both natural and anthropogenic sources, mercury exists mainly as
      three different molecular species: elemental, inorganic, and organic. Potential
      health risks have been reported from exposure to all forms; however, of
      particular concern for human exposure relate to the potent neurotoxic effects of
      methylmercury (MeHg), especially for the developing nervous system. The general
      population is primarily exposed to MeHg by seafood consumption. In addition, some
      pharmaceuticals, including vaccines, have been, and some continue to be, a
      ubiquitous source of exposure to mercurials. A significant controversy has been
      whether the vaccine preservative ethylmercury thiosalicylate, commonly known as
      thimerosal, could cause the development of autism. In this review, we have
      discussed the hypothesis that exposure to thimerosal during childhood may be a
      primary cause of autism. The conclusion is that there are no reliable data
      indicating that administration of vaccines containing thimerosal is a primary
      cause of autism. However, one cannot rule out the possibility that the individual
      gene profile and/or gene-environment interactions may play a role in modulating
      the response to acquired risk by modifying the individual susceptibility.

PMID- 19756913
TI  - A computerized tomography scan method for calculating the hernia sac and
      abdominal cavity volume in complex large incisional hernia with loss of domain.
AB  - Preoperative progressive pneumoperitoneum (PPP) is a safe and effective procedure
      in the treatment of large incisional hernia (size > 10 cm in width or length)
      with loss of domain (LIHLD). There is no consensus in the literature on the
      amount of gas that must be insufflated in a PPP program or even how long it
      should be maintained. We describe a technique for calculating the hernia sac
      volume (HSV) and abdominal cavity volume (ACV) based on abdominal computerized
      tomography (ACT) scanning that eliminates the need for subjective criteria for
      inclusion in a PPP program and shows the amount of gas that must be insufflated
      into the abdominal cavity in the PPP program. Our technique is indicated for all
      patients with large or recurrent incisional hernias evaluated by a senior surgeon
      with suspected LIHLD. We reviewed our experience from 2001 to 2008 of 23
      consecutive hernia surgical procedures of LIHLD undergoing preoperative
      evaluation with CT scanning and PPP. An ACT was required in all patients with
      suspected LIHLD in order to determine HSV and ACV. The PPP was performed only if
      the volume ratio HSV/ACV (VR = HSV/ACV) was >or=25% (VR >or= 25%). We have
      performed this procedure on 23 patients, with a mean age of 55.6 years (range 31
      83). There were 16 women and 7 men with an average age of 55.6 years (range 31
      83), and a mean BMI of 38.5 kg/m(2) (range 23-55.2). Almost all patients (21 of
      23 patients-91.30%) were overweight; 43.5% (10 patients) were severely obese
      (obese class III). The mean calculated volumes for ACV and HSV were 9,410 ml
      (range 6,060-19,230 ml) and 4,500 ml (range 1,850-6,600 ml), respectively. The
      PPP is performed by permanent catheter placed in a minor surgical procedure. The
      total amount of CO(2) insufflated ranged from 2,000 to 7,000 ml (mean 4,000 ml).
      Patients required a mean of 10 PPP sessions (range 4-18) to achieve the desired
      volume of gas (that is the same volume that was calculated for the hernia sac).
      Since PPP sessions were performed once a day, 4-18 days were needed for
      preoperative preparation with PPP. The mean VR was 36% (ranged from 26 to 73%).
      We conclude that ACT provides objective data for volume calculation of both
      hernia sac and abdominal cavity and also for estimation of the volume of gas that
      should be insufflated into the abdominal cavity in PPP.

PMID- 19756914
TI  - Lightweight mesh improves functional outcome in laparoscopic totally extra
      peritoneal inguinal hernia repair.
AB  - BACKGROUND: Prosthetic mesh reinforcement is standard practice for inguinal
      hernia repair but can cause considerable pain and stiffness around the groin and
      affect physical functioning. This has led to various types of mesh being
      engineered, with a growing interest in a lighter weight mesh. The aim of this
      prospective study was to compare the outcome after laparoscopic totally extra
      peritoneal (TEP) inguinal repair using new lightweight or traditional heavyweight
      mesh performed in a single specialist centre. METHODS: Between November 2004 and
      July 2005, 250 patients underwent laparoscopic TEP inguinal repair using either
      lightweight (Ultrapro, 30 g/m(2)) or heavyweight (Prolene, 100 g/m(2)) mesh.
      Follow-up data was obtained using case note review and telephone-based
      questionnaire. Patients were followed up within the early and late post-operative
      periods to assess any changes in outcome. RESULTS: Follow-up information was
      obtained for 188 (75%) out of 250 patients. There was no difference between
      lightweight and heavyweight groups in the incidence or severity of
      pain/discomfort at mean 4 and 15 months follow-up. There was significantly less
      interference with physical activity at short and long term follow-up in the
      lightweight group, in particular lifting (9% vs 21% at mean 4 months, Mann
      Whitney U, P = 0.024), walking (1% vs 11% at mean 15 months, Mann-Whitney U, P =
      0.006) and vigorous activities (7% vs 19% at mean 15 months, Mann-Whitney-U, P =
      0.012). There was no significant difference in awareness of mesh or stiffness in
      the groin. CONCLUSIONS: Laparoscopic TEP inguinal hernia repair with a
      lightweight mesh improves functional outcome in the short and long term. There
      was significantly less interference with all aspects of physical activity with
      the lightweight mesh. Pain in both groups was very mild, highlighting the
      benefits of laparoscopic surgery.

PMID- 19756915
TI  - Amyand's hernia with adenocarcinoid tumor.
AB  - The contents of an incarcerated inguinal hernia sac usually consist of small
      bowel or omentum. Amyand's hernia, the situation in which appendicitis is noted
      in the hernia sac, is a rare occurrence. Also, neoplasms of the appendix is quite
      uncommon. The occurrence of these two conditions together is even more rarely
      reported. We report the case of a 62-year-old male with these two diseases
      simultaneously. Incarcerated inguinal hernia was noted before operation. Amyand's
      hernia was noted during the operation. Adenocarcinoid tumor of the appendix was
      noted after the operation. Operative decisions were changed during the medical
      course.

PMID- 19756917
TI  - Behavioral modifications in northern bearded saki monkeys (Chiropotes satanas
      chiropotes) in forest fragments of central Amazonia.
AB  - We investigated behavioral differences among seven groups of northern bearded
      saki monkeys (Chiropotes satanas chiropotes) living in five forest fragments and
      two areas of continuous forest at the Biological Dynamics of Forest Fragments
      Project study area, located approximately 80 km north of Manaus, Brazil. We
      collected data in six research cycles from July-August 2003 to January 2005-April
      2006. When bearded saki monkeys were present in a study area, we followed the
      group from dawn until dusk for three consecutive days. Every 5 min, we conducted
      behavioral scans of all visible individuals. There was a positive relationship
      between forest size and group size, but animals in the small forest fragments
      lived at greater densities. Bearded saki monkeys in the smaller fragments spent
      more time resting, less time traveling, and less time vocalizing, but there was
      no relationship between forest size and the amount of time spent feeding. Our
      results indicate that the main behavioral differences among the groups are
      related to the amount of forest resources (e.g., fruit trees, space) available to
      the monkeys in the smaller fragments, as well as the resulting smaller group
      sizes. We stress the need to preserve large tracts of forest and provide
      connectivity between forest patches.

PMID- 19756916
TI  - The potential of optical proteomic technologies to individualize prognosis and
      guide rational treatment for cancer patients.
AB  - Genomics and proteomics will improve outcome prediction in cancer and have great
      potential to help in the discovery of unknown mechanisms of metastasis, ripe for
      therapeutic exploitation. Current methods of prognosis estimation rely on
      clinical data, anatomical staging and histopathological features. It is hoped
      that translational genomic and proteomic research will discriminate more
      accurately than is possible at present between patients with a good prognosis and
      those who carry a high risk of recurrence. Rational treatments, targeted to the
      specific molecular pathways of an individual's high-risk tumor, are at the core
      of tailored therapy. The aim of targeted oncology is to select the right patient
      for the right drug at precisely the right point in their cancer journey. Optical
      proteomics uses advanced optical imaging technologies to quantify the activity
      states of and associations between signaling proteins by measuring energy
      transfer between fluorophores attached to specific proteins. Forster resonance
      energy transfer (FRET) and fluorescence lifetime imaging microscopy (FLIM) assays
      are suitable for use in cell line models of cancer, fresh human tissues and
      formalin-fixed paraffin-embedded tissue (FFPE). In animal models, dynamic deep
      tissue FLIM/FRET imaging of cancer cells in vivo is now also feasible. Analysis
      of protein expression and post-translational modifications such as
      phosphorylation and ubiquitination can be performed in cell lines and are
      remarkably efficiently in cancer tissue samples using tissue microarrays (TMAs).
      FRET assays can be performed to quantify protein-protein interactions within FFPE
      tissue, far beyond the spatial resolution conventionally associated with light or
      confocal laser microscopy. Multivariate optical parameters can be correlated with
      disease relapse for individual patients. FRET-FLIM assays allow rapid screening
      of target modifiers using high content drug screens. Specific protein-protein
      interactions conferring a poor prognosis identified by high content tissue
      screening will be perturbed with targeted therapeutics. Future targeted drugs
      will be identified using high content/throughput drug screens that are based on
      multivariate proteomic assays. Response to therapy at a molecular level can be
      monitored using these assays while the patient receives treatment: utilizing re
      biopsy tumor tissue samples in the neoadjuvant setting or by examining surrogate
      tissues. These technologies will prove to be both prognostic of risk for
      individuals when applied to tumor tissue at first diagnosis and predictive of
      response to specifically selected targeted anticancer drugs. Advanced optical
      assays have great potential to be translated into real-life benefit for cancer
      patients.

PMID- 19756918
TI  - Hydroxyespintanol and schefflerichalcone: two new compounds from Uvaria
      scheffleri.
AB  - A chemical investigation of the petroleum ether extract and chloroform extract of
      the root of Uvaria scheffleri Diels (Annonaceae) led to the isolation of two new
      compounds, named hydroxyespintanol (1) and schefflerichalcone (2), together with
      eight known compounds (3-10). The structural elucidation of compounds 1 and 2 by
      spectroscopic studies is described. The cytotoxicity of the isolated compounds
      against human promyelocytic leukemia HL-60 cells was studied. Among these, 2'
      hydroxy-3',4',6'-trimethoxychalcone (5) exhibited cytotoxicity (IC(50) 12
      microM), and espintanol (3), which was the main ingredient, also showed some
      cytotoxicity (IC(50) 44 microM).

PMID- 19756919
TI  - Clinical impact of whole body FDG-PET for recurrent biliary cancer: a multicenter
      study.
AB  - OBJECTIVE: To evaluate the clinical usefulness of positron emission tomography
      (PET) using (18)F-fluorodeoxyglucose (FDG) in patients with follow-up or
      suspected recurrent biliary cancer in a multicenter study. METHODS: We performed
      a retrospective review of 50 patients who underwent FDG-PET (either integrated
      PET/CT or manual fusion of dedicated PET and CT) scans for post-treatment
      surveillance of biliary cancer. Recurrence was suspected in 40 of these patients
      on the basis of tumor marker levels, and/or findings of conventional imaging
      (group A). Clinical findings in the remaining 10 patients showed them to be
      disease-free (group B). The diagnostic performance and clinical impact of PET
      were analyzed. RESULTS: Recurrence was confirmed in 28 out of the 40 patients in
      group A, and 1 of the 10 patients in group B. Patient-based analysis showed that
      the sensitivity, specificity, and accuracy of PET for detecting recurrence were
      86% (25/29), 91% (19/21), and 88% (44/50), respectively. The one patient with
      recurrence in group B was correctly interpreted by PET. Positive test likelihood
      ratio and negative test likelihood ratio were increased from 1.69 to 9.05, and
      0.08 to 0.32, respectively, after PET study. The findings of PET resulted in a
      change of management for 10 out of the 50 patients (20%) by initiating an
      unplanned treatment strategy (n = 7), by obviating the need for planned
      diagnostic procedures (n = 2), or by changing the treatment plan (n = 1).
      CONCLUSION: FDG-PET/CT or PET with CT yielded helpful information in patients
      with suspected recurrent biliary cancer.

PMID- 19756920
TI  - HHV8-positive, HIV-negative multicentric Castleman's disease: early and sustained
      complete remission with rituximab therapy without reactivation of Kaposi sarcoma.
AB  - Multicentric Castleman's disease (MCD) is a rare lymphoproliferative disorder
      with systemic symptoms and poor prognosis and is characterized by an abnormal
      proliferation of polyclonal plasmablasts in the mantle zone of B-cell follicles.
      The disease is found primarily in chronic HIV carriers and is usually strictly
      associated with human herpes virus type 8 (HHV-8) coinfection, which is believed
      to play a key role in the pathogenesis of MCD. The disease is also diagnosed in
      HIV-negative patients, who are usually elderly or immunosuppressed; however, in
      about half of these cases, no evidence of HHV8 infection is found. The anti-CD20
      monoclonal antibody rituximab is now the preferred treatment for HIV-positive
      MCD. However, it is not clear whether rituximab is effective in HIV-negative
      patients with MCD, particularly in the HHV8-positive subset. We report here the
      clinical and biologic courses of two HIV-negative, HHV8-positive patients with
      MCD who were treated with rituximab. In both cases, a significant clinical
      improvement was observed after the first two infusions, which was shortly
      followed by a drop in HHV8 viremia to undetectable levels. Both patients
      underwent complete clinical remission, which persisted without relapse at 30 and
      9 months of follow-up, respectively. No reactivation of the Kaposi sarcoma found
      in a lymph node of one of the patients was observed. Our report, along with
      additional data present in the literature, suggests that rituximab may be an
      appropriate and safe first-line therapy for HIV-negative, HHV8-positive MCD.

PMID- 19756922
TI  - Recent trends of HER-2 examination and a new strategy   of trastuzumab therapy
      for primary and metastatic breast cancer.

PMID- 19756921
TI  - Expression of annexin II in experimental abdominal aortic aneurysms.
AB  - Annexin II is a receptor of tissue-type plasminogen activator (t-PA). We have
      previously identified annexin II by immunolocalization in human atherosclerotic
      abdominal aortic aneurysms (AAAs). To investigate possible interactions between
      annexin II and AAA development, we examined annexin II mRNA and protein
      expression in a rat model of experimental AAA. AAAs were induced in rats by
      transient aortic infusion of elastase. The rats were divided into three groups: a
      saline-treated control group, a group with 15-min elastase infusion, and a group
      with 30-min elastase infusion. The 15-min elastase-infused group had smaller
      aneurysms and more preserved media than the 30-min elastase-infused group.
      Immunohistochemistry showed that annexin II expression was increased in the
      thickened intima and media of AAA rats as compared with the media of control
      rats. Furthermore, annexin II was colocalized with macrophages and smooth muscle
      cells. Quantitative real-time polymerase chain reaction showed that annexin II
      mRNA levels were up-regulated only in the smaller aneurysm group compared with
      the control group. In contrast, t-PA mRNA levels were increased in both the 15-
      and 30-min elastase-infused groups as compared with the control group. These
      results demonstrate various levels of annexin II expression within the aortic
      wall of rats with experimental AAAs. It has been suggested that alteration of
      fibrinolytic activity regulated by annexin II within the aortic wall may be
      associated with aneurysm formation.

PMID- 19756923
TI  - Comprehensive geriatric assessment in elderly breast cancer patients.
AB  - Treatment of elderly patients with breast cancer is limited by the lack of
      evidence-based medicine due to exclusion of elderly persons from clinical studies
      and the difficulty of decision-making in an elderly population comprising
      subjects with heterogeneous health backgrounds. Individual variation of health
      conditions is larger in elderly patients than in young people. Since the risk
      benefit balance of treatment depends on the health background, judgment of the
      vulnerability of individual patients is required in treatment planning. The
      comprehensive geriatric assessment (CGA) is a tool for acquisition of information
      for design of a cancer treatment plan based on evaluation of the vulnerability of
      elderly patients from various perspectives. The domains of the CGA include
      physical function, comorbidity, cognitive function, psychological status, social
      support system, nutrition, and medication. The CGA can be used to predict
      survival and adverse events; to identify health problems that cannot be detected
      based on medical history or examination; to recognize new problems that emerge
      during course observation; and to improve psychological conditions. However,
      application of the CGA in routine clinical practice requires establishment of a
      consensus regarding the survey method, evaluation scale, and use of results in
      decision-making. A prospective investigation of the CGA as an outcome index in
      elderly breast cancer patients is required to address these issues.

PMID- 19756924
TI  - The impact of sentinel lymph node biopsy in patients with a core biopsy diagnosis
      of ductal carcinoma in situ.
AB  - BACKGROUND: When ductal carcinoma in situ (DCIS) is found on core biopsy,
      histological underestimation can occur due to sampling error. When an invasive
      cancer is subsequently found, another operation is required for nodal staging.
      Sentinel lymph node biopsy (SLNB) enables nodal staging at the same operation. We
      examine the value of SLNB in patients with a preoperative diagnosis of DCIS
      focusing on the need for reoperation. METHODS: Patients with a preoperative core
      biopsy of DCIS underwent SLNB at the time of definitive surgery. The results of
      SLNB in relation to histological upstaging were analyzed. RESULTS: One hundred
      and seven patients with a core biopsy diagnosis of DCIS underwent simultaneous
      SLNB at the time of definitive surgery. SLNB was successful in 103 patients
      (96.3%) and 12 (11.7%) had SLN metastases. Thirty-two patients (29.9%) had
      histological upstaging and SLN was positive in nine (28.1%). Seventy-five
      patients had "pure DCIS" but three (4%) had SLN metastases. The presence of a
      palpable mass and radiological mass lesion were associated with histological
      upstaging. If SLNB were not performed, 32 patients (29.9%) with upstaging would
      require another surgery to stage the axilla. In the present series, 84% of these
      patients had appropriate axillary staging without the need for a second
      operation. CONCLUSION: Underestimation of invasive disease was frequent on core
      biopsy. Performing SLNB during definitive surgery allowed correct nodal staging
      in a single operation. SLN metastasis was rare in patients with "pure DCIS" on
      final pathology. However, additional systemic treatment may be indicated for
      patients with SLN micrometastases.

PMID- 19756925
TI  - Pure mucinous carcinoma with axillary lymph node metastasis in a male breast.
AB  - Pure mucinous carcinoma of the male breast is an extremely uncommon malignant
      breast neoplasm and usually occurs at advanced age. It is characterized by a
      higher degree of mucus production, a more benign behavior, a lower incidence of
      metastatic nodal involvement, and a subsequent higher survival rate. We describe
      such a case of a 59-year-old male, who displayed a gradually growing retroareolar
      tumor of the right breast. The tumor was well demarcated and had a soft
      consistency with a gelatinous appearance. Based on the preoperative clinical
      identification of right axillary lymphadenopathy, the patient eventually
      underwent right modified radical mastectomy and right axillary nodal dissection.
      Regarding histological findings, the neoplasm corresponded to a pure mucinous
      carcinoma with axillary lymph node metastasis. Although lymph node metastasis of
      pure mucinous carcinoma of the breast is rare, it is essential to perform careful
      clinical examination when the primary breast mass is suspicious for mucinous
      carcinoma, because the presence of axillary lymphadenopathy will subsequently
      define the proper choice of therapeutic strategy.

PMID- 19756926
TI  - High safety profile and activity of oral vinorelbine in an elderly patient with
      metastatic breast cancer.
AB  - Visceral metastases of breast cancer have been commonly treated with "aggressive"
      anthracyclines/taxanes-based chemotherapy. In contrast, this case report concerns
      an elderly patient with advanced breast cancer (pleural effusion, peritoneal
      carcinosis, and bone metastases) who firmly declined intravenous chemotherapy and
      was treated for a long time (28 months) with oral vinorelbine. The oral
      formulation of this drug had activity and a high safety profile, enabling the
      patient's wishes to be respected.

PMID- 19756927
TI  - Association between interpersonal relationship among high-school students and
      mental health.
AB  - OBJECTIVES: Adolescents have many anxieties, and having someone to consult is
      important for them to maintain their mental health. This study examines: whether
      students have someone to consult; if they have, whether there are differences in
      their depressive state and in their degree of satisfaction with their school
      lives depending on whom they consult; and how their mental health is affected by
      their human relations. METHODS: Persons whom high-school students consult about
      their worries, Depression Self-Rating Scale for Children (DSRS-C), and
      satisfaction of high-school students with their school lives were surveyed in
      2,646 students of public high schools in A Prefecture, and the persons selected
      for consultation were classified into four groups ("no one," "friends," "adults,"
      and "friends and adults") and analyzed. RESULTS: In terms of whom they consult we
      found that high-school students, especially girls, frequently consult "friends
      and adults." Mean DSRS-C score was significantly higher for those who consulted
      "no one" than for those who consulted "friends" or "friends and adults."
      Regarding hopelessness, the mean score of those who consulted "no one" was
      significantly higher than for those who consulted "friends and adults." Those who
      consulted "no one" had significantly lower mean score for satisfaction with
      school life than did those who consulted "friends and adults." CONCLUSIONS: Most
      of the students selected "friends and adults" for persons to consult, but boys
      were more likely to have "no one" to consult. Students (boys and girls) having no
      one to consult are likely to be more depressive and less satisfied with their
      school lives.

PMID- 19756928
TI  - Association between dioxin concentrations in breast milk and food group intake in
      Vietnam.
AB  - OBJECTIVES: To clarify the association between dioxin concentrations in breast
      milk and food group intake in herbicide-sprayed and nonsprayed areas in Vietnam.
      METHODS: This survey was conducted in August 2007 in sprayed and nonsprayed
      areas, respectively. The interviews were performed using a questionnaire to
      obtain information on personal characteristics and usual dietary intake. Eighty
      mothers of sprayed area and 42 mothers of nonsprayed area participated in the
      study. Breast milk was analyzed for concentration of polychlorinated dibenzo-p
      dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). RESULTS: Multiple
      regression analysis showed that location (sprayed or nonsprayed area) has the
      highest association with the toxic equivalents (TEQ)-PCDDs, TEQ-PCDFs, and TEQ
      Total rather than other factors. In the sprayed area, the adjusted R (2) values
      of regression were approximately 0.1. On the other hand, the adjusted R (2)
      values in the nonsprayed areas were higher than those in the sprayed area, i.e.,
      between 0.2 and 0.3, and showed that there were significant associations with
      body mass index (BMI) in all models. CONCLUSIONS: Dioxin exposure was less
      affected by usual dietary intake in the sprayed area than in the nonsprayed area
      in Vietnam. It was clear that past exposure rather than present dietary intake
      may affect present dioxin concentrations in breast milk in the sprayed area in
      Vietnam. This study suggests that present dioxin concentrations in breast milk
      were maintained by continuous past exposure even after 30-40 years had passed.

PMID- 19756929
TI  - The modulation of immunological activities in human NK cells by extracts of
      ginkgo.
AB  - OBJECTIVE: To investigate the association between extracts of ginkgo and the
      immune system by determining changes in natural killer (NK) cell activity and
      surface markers in human NK cells and by analyzing for surface markers. METHODS:
      Natural killer cell activity was determined in peripheral blood samples of three
      subjects who received ginkgo daily (250 ml/day; (ginkgo concentration 40 mg/ml)
      for 14 days by the non-radioisotopic Europium (non-RI Eu) release assay.
      Peripheral blood samples were taken three times during the study period: before
      ginkgo sample ingestion, on day 7 after ginkgo ingestion, and on day 14 after
      ginkgo ingestion). The peripheral blood samples were also analyzed for surface
      markers (CD56, CD3, CD19, CD20, CD4, CD8) using a fluorescence-activated cell
      sorter (FACScalibur). RESULTS: The non-RI Eu release assay revealed that the
      ingestion of ginkgo extracts elevated NK cell activity in the subjects, with the
      highest activity recorded following treatment with an extract at a concentration
      of 400-800 MUg/ml. The analysis for surface markers using the FACScalibur showed
      that the expression of CD56 (NK cell surface marker) was elevated and the
      expression of CD19 had dropped in our subjects by day 14 of ginkgo ingestion.
      There was no significant difference in surface markers after 7 days of ginkgo
      ingestion. CONCLUSION: Ginkgo extracts were found to affect immunological
      activities and surface markers (CD56) in human NK cells. Our results also reveal
      an optimal range of ginkgo concentration-from 400 to 800 MUg/ml-within which its
      immunopotentiating activity is highest. It took at least 2 weeks to affect
      surface markers in human NK cells after ginkgo ingestion, and surface markers
      were not affected after 7 days of ginkgo ingestion.

PMID- 19756931
TI  - Reoperation of the proximal aorta: impact of presternotomy extracorporeal
      circulation on clinical outcomes.
AB  - PURPOSE: Adverse events can occur during a sternotomy for reoperation of the
      proximal aorta. Presternotomy extracorporeal circulation is often employed to
      avoid catastrophic events. The purpose of this study was to investigate the
      impact of presternotomy extracorporeal circulation on clinical outcomes of redo
      proximal aortic surgery. METHODS: Between January 1990 and December 2005 a total
      of 21 aneurysms or dissections of the proximal aorta were repaired via a repeat
      sternotomy. Extracorporeal circulation was established before the sternotomy in 9
      (49%) patients and after the sternotomy in 12 (51%) patients. RESULTS: There were
      no statistically significant differences in the age, sex, emergency surgery,
      chronic obstructive pulmonary disease, and renal function between the groups.
      Femoral cannulation was used more often in the presternotomy extracorporeal
      circulation group (8/9, 89% vs. 1/12, 8.3%; P = 0.000). The difference in the
      pump time did not reach a statistically significant level. The 30-day and in
      hospital mortality rates were 11% (1/9) and 11% (1/9) in the presternotomy
      extracorporeal circulation group and 0% (0/12) and 17% (2/12) in the
      poststernotomy extracorporeal circulation group. There were no statistically
      significant differences in stroke, respiratory failure, myocardial infarction, or
      renal failure. There was a trend toward a longer hospital stay in the
      presternotomy extracorporeal circulation group (85.8 vs. 48.1 days; P = 0.06).
      CONCLUSION: Presternotomy extracorporeal circulation was not associated with any
      major adverse outcomes such as death, stroke, or renal failure.

PMID- 19756930
TI  - Lung cancer-associated tumor antigens and the present status of immunotherapy
      against non-small-cell lung cancer.
AB  - Despite recent advances in surgery, irradiation, and chemotherapy, the prognosis
      of patients with lung cancer is still poor. Therefore, the development and
      application of new therapeutic strategies are essential for improving the
      prognosis of this disease. Significant progress in our understanding of tumor
      immunology and molecular biology has allowed us to identify the tumor-associated
      antigens recognized by cytotoxic T lymphocytes. Immune responses and tumor
      associated antigens against not only malignant melanoma but also lung cancer have
      been elucidated at the molecular level. In a theoretical sense, tumor eradication
      is considered possible through antigen-based immunotherapy against such diseases.
      However, many clinical trials of cancer vaccination with defined tumor antigens
      have resulted in objective clinical responses in only a small number of patients.
      Tumor escape mechanisms from host immune surveillance remain a major obstacle for
      cancer immunotherapy. A better understanding of the immune escape mechanisms
      employed by tumor cells is necessary before we can develop a more effective
      immunotherapeutic approach to lung cancer. We review recent studies regarding the
      identification of tumor antigens in lung cancer, tumor immune escape mechanisms,
      and clinical vaccine trials in lung cancer.

PMID- 19756932
TI  - Usefulness of suplatast tosilate for chronic cough following lung cancer surgery.
AB  - OBJECTIVE: Chronic dry cough is reported to occur in about 25% of patients
      following lung cancer surgery. Experimental data suggest that it may be caused
      mainly by stimulation of C-fibers, which are widely distributed to the lower
      trachea and bronchi. We assessed the clinical usefulness of suplatast tosilate
      (IPD) for chronic dry cough after lung cancer surgery. METHODS: The subjects were
      patients with stage I lung cancer who had undergone lobectomy combined with
      mediastinal lymph node dissection. IPD was administered orally at 400 mg daily,
      and its efficacy was evaluated by patient interview 1, 2, and 3 months after the
      start of treatment. The subjects were 19 patients, and the duration of cough
      before entering the study was 393.2 days. RESULTS: The response rate was 84.2%
      (16/19) 1 month after the start of treatment. It seems that IPD inhibits cough
      resulting from stimulation of the bifurcated trachea with a high content of C
      fibers. CONCLUSION: The present study suggested the efficacy of IPD for
      controlling chronic dry cough after lung cancer surgery.

PMID- 19756933
TI  - Apicoaortic valved conduit with an apical connector for aortic stenosis with a
      calcified aorta.
AB  - We report a case of apicoaortic bypass using an apical connector for severe
      aortic stenosis. A 74-year-old woman suffered from severe aortic stenosis, with a
      small aortic annulus and a severely calcified aorta. A valved conduit with an
      apical connector was placed between the left ventricular apex and the descending
      thoracic aorta because the risk of aortic valve replacement was high. Use of an
      apical connector facilitated a secure connection between the conduit and the left
      ventricular apex. The pressure gradient across the native aortic valve fell from
      64 mm Hg before the operation to 19 mm Hg afterward. Apicoaortic bypass using the
      apical connector is a reliable option for relieving obstruction of the left
      ventricular outflow tract in the presence of aortic stenosis when aortic valve
      replacement is a high risk.

PMID- 19756934
TI  - Use of a Matsui-Kitamura stent-graft for endovascular repair of patent ductus
      arteriosus in an adult patient.
AB  - Open surgical repair of patent ductus arteriosus is difficult in the case of
      elderly patients because of calcification of the duct and the possibility of
      rupture. Furthermore, endovascular repair with the use of a coil or an occluding
      device poses problems such as residual shunt or migration of the device. We
      describe a case wherein closure of a large patent ductus arteriosus in an adult
      patient was achieved using a Matsui-Kitamura curved nitinol stent-graft.

PMID- 19756935
TI  - Fulminant apical ballooning syndrome after replacement of a prosthetic aortic
      valve.
AB  - A 70-year-old woman was readmitted to our hospital with a fever of 39 degrees C
      on the 30th day after replacement of a prosthetic aortic valve. She required
      percutaneous cardiopulmonary support for her heart failure and was weaned after 7
      days. Echocardiography revealed an akinetic and aneurysmally dilated left
      ventricular apex and hyperdynamic basal segments. This case indicates that
      fulminant apical ballooning syndrome might be added to the list of potential
      complications after cardiac surgery.

PMID- 19756936
TI  - Surgical treatment for papillary fibroelastoma of the aortic valve.
AB  - Although cardiac papillary fibroelastomas are benign tumors, they have the
      potential to cause life-threatening complications such as stroke and myocardial
      infarction and may even lead to sudden cardiac death. We report a case of
      surgical treatment for a papillary fibroelastoma of the aortic valve. The patient
      was a 62-year-old woman who was asymptomatic for cardiac papillary fibroelastoma.
      Echocardiography demonstrated a mobile, rounded mass on the left coronary cusp of
      the aortic valve. The patient underwent surgical excision, had an uneventful
      recovery, and was discharged 10 days after the operation. Pathology examination
      confirmed papillary fibroelastoma. Surgical excision of the tumor is recommended
      for patients with symptoms, but the treatment of asymptomatic patients is
      controversial. We believe that surgical treatment should be performed if the
      tumor is mobile.

PMID- 19756937
TI  - Large bronchial granular cell tumor.
AB  - We report a 20-year-old woman who underwent complete resection of a granular cell
      tumor (GCT). On chest computed tomography (CT) scan, a mass with a maximum
      diameter of 36 mm at the lower bronchus with atelectasis of the right lower lobe
      was noted. Bronchoscopic examination revealed a whitish mass in the truncus
      intermedius, and the middle and lower bronchus were unable to be seen. A
      cytopathological examination of the mass revealed GCT. A right middle and lower
      lobectomy was performed via a posterolateral thoracotomy. Microscopically, the
      tumor was composed of polygonal cells with oxyphilic granular cytoplasm and small
      ovoid nuclei. The cytoplasm of the neoplastic cells was positive for S-100
      protein and neuron-specific enolase. The patient's postoperative course was
      uneventful, and she was asymptomatic after 4 months. A large bronchial GCT is
      rare, which is why we report this case.

PMID- 19756938
TI  - Thoracic and cardiovascular surgery in Japan during 2007. Annual report by the
      Japanese Association for Thoracic Surgery.

PMID- 19756940
TI  - Pre-meiotic bands and novel meiotic spindle ontogeny in quadrilobed sporocytes of
      leafy liverworts (Jungermannidae, Bryophyta).
AB  - Indirect immunofluorescence and confocal microscopy were used to study the
      nucleation and organization of microtubules during meiosis in two species of
      leafy liverworts, Cephalozia macrostachya and Telaranea longifolia. This is the
      first such study of sporogenesis in the largest group of liverworts important as
      living representatives of some of the first land plant lineages. These studies
      show that cytoplasmic quadrilobing of pre-meiotic sporocytes into future spore
      domains is initiated by girdling bands of gamma-tubulin and microtubules similar
      to those recently described in lobed sporocytes of simple thalloid liverworts.
      However, spindle ontogeny is not like other liverworts studied and is, in fact,
      probably unique among bryophytes. Following the establishment of quadrilobing,
      numerous microtubules diverge from the bands and extend into the enlarging lobes.
      The bands disappear and are replaced by microtubules that arise from gamma
      tubulin associated with the nuclear envelope. This microtubule system extends
      into the four lobes and is gradually reorganized into a quadripolar spindle, each
      half spindle consisting of a pair of poles straddling opposite cleavage furrows.
      Chromosomes move on this spindle to the polar cleavage furrows. The reniform
      daughter nuclei, each curved over a cleavage furrow, immediately enter second
      meiotic division with spindles now terminating in the lobes. Phragmoplasts that
      develop in the interzones among the haploid tetrad nuclei guide deposition of
      cell plates that join with the pre-meiotic furrows resulting in cleavage of the
      tetrad of spores. These observations document a significant variation in the
      innovative process of sporogenesis evolved in early land plants.

PMID- 19756941
TI  - Microwave irradiation as a versatile tool for increasing reaction rates and
      yields in synthesis of optically active polyamides containing flexible L-leucine
      amino acid.
AB  - In this investigation, a series of thermally stable and optically active
      polyamides (PA)s containing bulky pendant chiral functionality from
      polymerization of a diacid monomer containing rigid phthalimide and flexible L
      leucine groups, (2S)-5-[4-(4-methyl-2
      phthalimidylpentanoylamino)benzoylamino]isophthalic acid with several aromatic
      and aliphatic diisocyanates such as 4,4'-methylenebis(phenyl isocyanate),
      toluylene-2,4-diisocyanate, isophorone diisocyanate, and hexamethylene
      diisocyanate under gradual heating method were prepared and compared with
      microwave-assisted polycondensation method. The polymerization reactions occurred
      rapidly under microwave irradiation and produced a series of PAs with good yields
      and moderate inherent viscosities of 0.26-0.68 dL/g. All of the new PAs showed
      good solubility and were readily dissolved in aprotic organic solvents. The
      resulting polymers were characterized by FT-IR, (1)H NMR spectroscopy, and
      elemental analysis technique. Thermal stability and thermal properties of PAs
      were evaluated by thermogravimetric analysis and differential scanning
      calorimetry. The interpretation of kinetic parameters (E, Delta H, Delta S, and
      Delta G) of thermal decomposition stages have been evaluated using Coats-Redfern
      equations.

PMID- 19756942
TI  - Tryptophan and iodothyronine transport interactions in HepG2 human hepatoma
      cells.
AB  - This study identifies interactions between transport of the aromatic amino acid
      L: -tryptophan (Trp) and thyroid hormones (TH) in HepG2 human hepatoma cells. The
      major portion of Trp uptake in HepG2 cells occurs via the NEM-sensitive amino
      acid transport System L2 (consistent with hepatic LAT3 expression), with a
      smaller aromatic-AA selective System T (MCT10) component. LAT3 and MCT10 mRNA
      were both detected in HepG2 cells. Uptake of TH does not involve System L2, but a
      significant portion of T(3) uptake is mediated by System T, alongside a
      taurocholate-sensitive organic anion transporter. T(4) uptake into HepG2 cells
      appears to be mediated principally by organic anion/monocarboxylate transporters,
      with smaller contributions by System T and receptor-mediated endocytosis. TH-Trp
      transport interactions in liver cells centre on System T which, due to a
      perivenous localisation alongside deiodinase 1, may impact on hepatic T(3)
      generation and release.

PMID- 19756943
TI  - Plasma catecholamine and nephrine responses following 7 weeks of sprint cycle
      training.
AB  - The catecholamine metabolites normetanephrine (NMET) and metanephrine (MET)
      increase in response to acute exercise. However, changes in catecholamine
      'nephrines' during sprint training are unclear. Therefore, the aim of this study
      was to examine the plasma nephrine and catecholamine (noradrenaline, NA;
      adrenaline, AD) responses to a laboratory-based cycle test before and after a 7
      week period of cycle sprint training. Ten healthy men completed a 2-min cycle
      test at a power output equivalent to 110% of pre-training VO(2)max before and
      after 7 weeks of laboratory based sprint cycle training, three times per week.
      Resting and post-sprint venous blood samples were taken. Resting plasma nephrines
      and catecholamines increased significantly following exercise (P < 0.05). Post
      exercise NA and NMET were reduced after training (P < 0.05) and a trend for a
      reduction in AD (P = 0.09) and MET (P = 0.07) was observed. The results
      demonstrate a reduction in exercise-induced increases in plasma nephrine
      concentrations following sprint training. This suggests catechol-O-methyl
      transferase activity is coupled to high intensity cycle exercise. These findings
      may aid in the understanding of catecholamine regulation during high intensity
      exercise and sprint training.

PMID- 19756944
TI  - Patent foramen ovale in patients with tension headache: is it as common as in
      migraineurs? An age- and sex-matched comparative study.
AB  - The association of patent foramen ovale (PFO) and atrial septal aneurysm (ASA)
      with migraine headache attack (MHA) has been clearly shown. The same findings
      have been recently demonstrated also in cluster headache. Although tension-type
      headaches (TTH) are the most common kind of headache, their association with
      these atrial septal abnormalities has never been studied before. The study was
      conducted to clarify whether there was a significant association between the
      presence of such atrial septal abnormalities and tension headache, when compared
      with migraineurs. One hundred consecutive patients with migraine and 100 age- and
      sex-matched subjects with TTH and 50 healthy volunteers with no headache were
      enrolled in the study and underwent a complete transesophageal echocardiographic
      study with contrast injections at rest and with the Valsalva maneuver. There was
      no significant difference between the age and the sex of the participants of the
      three groups. The overall prevalence of PFO was 23% in patients with TTH and that
      of large PFOs was only 11%. The 23% prevalence of PFO in patients with TTH was
      not statistically different from 16% found in our normal control group.
      Furthermore, we found a significantly higher prevalence of PFO in migraineurs
      (50%) when compared with patients with tension headache (p < 0.001). This was
      also true for the collective presence of large PFOs and ASAs (35%) (p < 0.001).
      Although atrial septal anomalies have an association with MHA, they do not have a
      significant association with TTH.

PMID- 19756945
TI  - The central analgesia induced by antimigraine drugs is independent from Gi
      proteins: superiority of a fixed combination of indomethacin, prochlorperazine
      and caffeine, compared to sumatriptan, in an in vivo model.
AB  - A hypofunctionality of Gi proteins has been found in migraine patients. The fixed
      combination of indomethacin, prochlorperazine and caffeine (Indoprocaf) is a drug
      of well-established use in the acute treatment of migraine and tension-type
      headache. The aim of this study was to investigate if Indoprocaf was able to
      exert its central antinociceptive action when Gi proteins activity is abolished
      by pertussis toxin (PTX), compared to its single active ingredients and to
      sumatriptan. The mice model of abdominal constriction test induced by an i.p.
      injection of a 0.6% solution of acetic acid was used. The study showed that
      Indoprocaf (a fixed combination of indomethacin 1 mg/kg, prochlorperazine 1 mg/kg
      and caffeine 3 mg/kg, s.c.) and sumatriptan (20 mg/kg, s.c.) exert their central
      antinociceptive action independently from the Gi proteins. In addition, the
      antinociceptive efficacy of Indoprocaf in this study was statistically superior
      to that of sumatriptan. This study also showed that the single active ingredients
      of Indoprocaf, indomethacin (1 mg/kg, s.c.), prochlorperazine (1 mg/kg, s.c.) and
      caffeine (3 mg/kg, s.c.), were able to exert their central antinociceptive action
      independently from the Gi proteins. However, Indoprocaf at analgesic doses was
      able to abolish almost completely the abdominal constrictions, with a
      statistically higher efficacy compared to the single active ingredients, showing
      an important synergic effect of Indoprocaf. This synergic effect was evident not
      only when Gi proteins activity was abolished by PTX, but also under control
      condition, when Gi proteins were active. This study suggests that the central
      antinociceptive action induced by antimigraine drugs is independent from Gi
      proteins.

PMID- 19756947
TI  - Contrast-enhanced ultrasonography (CEUS) immediately after percutaneous ablation
      of hepatocellular carcinoma.
AB  - PURPOSE: This study evaluated the effectiveness of contrast-enhanced ultrasound
      (CEUS), performed immediately after percutaneous ethanol injection (PEI) or
      radiofrequency thermal ablation (RFTA), by comparing results with the computed
      tomography (CT) follow-up. MATERIALS AND METHODS: Sixty-nine consecutive patients
      with a diagnosis of hepatocellular carcinoma (HCC) were included in this
      prospective study. All patients underwent PEI or RFTA. After treatment, three
      CEUS enhancement patterns were observed: isovascular, hypovascular and avascular,
      which were compared with the CT findings. Sensitivity of the avascular pattern at
      CEUS and effectiveness of the ablative procedures were evaluated and compared
      with the chi-square test. RESULTS: Ninety hypervascular HCCs, with a mean
      diameter of 2.6 cm (0.5-4.9 cm), underwent PEI (n=54) and RFTA (n=36). In the
      first group, CT identified complete necrosis in 28/54 (52%) lesions, 21 (75%) of
      which had avascular, one (4%) isovascular and six (21%) hypovascular patterns at
      CEUS. In the second group, CT showed complete necrosis in 31/36 (86%) lesions,
      all (100%) of which had a corresponding avascular pattern at CEUS. Sensitivity,
      specificity, positive predictive value, negative predictive value and accuracy of
      the avascular pattern at CEUS compared with CT findings were 75%, 69%, 72%, 72%
      and 72% for PEI and 100%, 20%, 89%, 100% and 89%, for RFTA, respectively. A
      statistically significant difference (p<0.05) between the sensitivity of CEUS
      after PEI and after RFTA and between the necrosis obtained by RFTA and PEI were
      observed. CONCLUSIONS: CEUS performed immediately after percutaneous ablation of
      hepatocellular carcinoma to evaluate treatment efficacy is compulsory in the case
      of RFTA but not for PEI.

PMID- 19756948
TI  - Role of fetal MRI in the diagnosis of cerebral ventriculomegaly assessed by
      ultrasonography.
AB  - PURPOSE: To evaluate the additional diagnostic value of fetal MRI to evaluate
      cerebral ventriculomegaly assessed by ultrasonography (US) for the possibility to
      change the diagnosis, the counseling and the management of pregnancy. MATERIALS
      AND METHODS: From february 2006 to october 2008, we studied 55 pregnant women by
      fetal MRI (mean age 28 years), 4 with twin pregnancy, for a total of 59 fetuses
      with mean gestational age of 27 weeks. The number of fetuses affected by
      ventriculomegaly assessed by US was 55. All fetuses had a US diagnosis of
      ventriculomegaly: 29 fetuses with isolated ventriculomegaly and 26 fetuses with
      ventriculomegaly associated with CNS (central nervous system) abnormalities (18)
      and with no CNS abnormalities (8). RESULTS: The findings showed that the two
      techniques are substantially in agreement in defining the degree of VM, with the
      exception of some cases in which the disagreement could be attributed to the
      possible progression of the dilatation between the US and MRI examinations, which
      sway between two days and two weeks. We proved a low correlation between US and
      MRI in the evaluation of ventriculomegaly associated either with CNS or non-CNS
      anomalies: in fact while fetal MRI detected 26/55 (47,3%) VM associated with CNS
      anomalies, US demonstrated only 18/55(32,7%). Referring to VM associated with non
      CNS anomalies, MRI diagnosed 10/55 cases (18,2%) compared to 8/55 fetuses (14,5%)
      showed by US. CONCLUSIONS: Our experience demonstrated that fetal MRI has an
      important role as adjunctive tool to sonography in the evaluation of cerebral
      ventriculomegaly for the additional informations given to parents and for the
      possibility to change the diagnosis, the counseling and the management of
      pregnancy.

PMID- 19756949
TI  - The use of a retrograde fixed-angle intramedullary nail for tibiocalcaneal
      arthrodesis after severe loss of the talus.
AB  - Tibiocalcaneal arthrodesis may be the only means of obtaining a painless and
      stable limb when there is loss of the talus. We present the early results of a
      prospective study on tibiocalcaneal arthrodesis using a latest-generation
      retrograde intramedullary nail. In the period 2006-2007, nine patients underwent
      tibiocalcaneal arthrodesis with retrograde intramedullary nailing. Five of these
      patients had infection-related loss of the talus. SF-36, AOFAS ankle-hindfoot,
      and Mazur Ankle Arthrodesis scores were obtained pre-fusion, and at 6 weeks, 6
      months and 1 year post-fusion. The patients were also followed up clinically and
      radiologically. Previous surgical procedures, chronic musculoskeletal problems
      and other comorbidities, and complications were recorded and analyzed. All
      patients were available for initial follow-up and were subjectively satisfied
      with their outcomes. Solid fusion was achieved and fully confirmed in nine cases.
      One subject died 8 weeks postoperatively of a pulmonary embolism. One patient had
      recurrent infection. At 1 year, only one patient still needed NSAIDs regularly
      for pain relief. The AOFAS score improved significantly (P = 0.012) from 32.1 pre
      fusion to 71.5 points at 1 year as did the Mazur score, which rose by 31.2 to
      72.5 points at 1 year (P = 0.012). The SF-36 score improved significantly in the
      domains physical functioning, role limitations due to physical problems, bodily
      pain, vitality, social functioning and mental health, as did the Physical
      Component Summary Score. Retrograde intramedullary nailing for tibiocalcaneal
      arthrodesis can produce a good outcome. However, in the presence of infection,
      patient selection for intramedullary procedures must be carefully considered on a
      case-by-case basis.

PMID- 19756950
TI  - New direct thrombin inhibitors.
AB  - Direct thrombin inhibitors (DTIs) are a class of anticoagulants that bind
      selectively to thrombin and block its interaction with its substrates. Dabigatran
      etexilate and AZD0837, the new generation of DTIs, are now under intense
      development, and are potentially of great interest for internists. Dabigatran
      etexilate is a potent, non-peptidic small molecule that specifically and
      reversibly inhibits both free and clot-bound thrombin by binding to the active
      site of thrombin molecule. It has been already licensed in the European Union and
      in Canada for the prevention of VTE in patients undergoing hip- and knee
      replacement surgery. Ongoing trials are evaluating its efficacy and safety for
      the treatment of deep venous thrombosis and pulmonary embolism, primary and
      secondary prevention of VTE, prevention of systemic embolism in patients with non
      valvular atrial fibrillation, and prevention of cardiac events in patients with
      acute coronary syndromes. AZD0837 is the prodrug of ARH06737, a potent,
      competitive, reversible inhibitor of free and fibrin-bound thrombin. At present,
      only limited, preclinical, phase I and phase II clinical data have been
      presented. The drug has now entered a phase III clinical program in the
      population of patients with atrial fibrillation. Their properties and the oral
      administration render these compounds, theoretically, more convenient than both
      vitamin K antagonist and low molecular weight heparins. However, only reports
      from clinical practice patterns over the next months and years will tell us how
      and when to use the new DTIs.

PMID- 19756951
TI  - Atrial fibrillation in a pregnant woman with a normal heart.

PMID- 19756952
TI  - A new approach to resident morning report: introducing "VAVUM".

PMID- 19756954
TI  - Noncompaction of ventricular myocardium in an elderly woman.

PMID- 19756955
TI  - Hepcidin mutation in a beta-thalassemia major patient with persistent severe iron
      overload despite chelation therapy.

PMID- 19756956
TI  - Neutral endopeptidase is a myristoylated protein.
AB  - Neutral endopeptidase (NEP) is a cell-surface peptidase normally expressed by
      prostate epithelial cells and lost in ~50% of primary prostate cancers. NEP
      directly associates with multiple proteins at the cell surface including
      Ezrin/Radixin/Moesin (ERM) proteins and the PTEN tumor suppressor protein.
      Analysis of the N-terminal sequence of the NEP cytosolic domain (N-terminal
      MGKSESQMDI TDINTPKPKK KQRWTR) identified a myristoylation consensus site.
      Mutation of Gly-2 to Arg significantly decreased (3)H-myristoylation activity,
      and correlated with translocation of NEP from the plasma membrane to a
      perinuclear domain as demonstrated by immunofluorescence staining and Western
      blotting with an NEP-specific antibody. Removal of this myristoylation residue
      did not affect NEP enzymatic specific activity. Myristoylated NEP recruited more
      PTEN protein to the cell membrane fraction than unmyristoylated NEP. These data
      demonstrate that NEP is myristoylated at Gly-2 and that this modification is an
      intrinsic signal for membrane targeting.

PMID- 19756957
TI  - Neonatal cardiac mitochondria and ischemia/reperfusion injury.
AB  - Postnatal maturation of the heart is characterized by decreasing tolerance to
      ischemia/reperfusion (I/R) injury associated with significant changes in
      mitochondrial function. The aim of this study is to test the hypothesis that the
      role of the mitochondrial membrane permeability transition pore (MPTP) in the I/R
      injury differs in the neonatal and in the adult heart. For this purpose, the
      effect of blockade of MPTP on the degree of I/R injury and the sensitivity of
      MPTP to swelling-inducing agents was compared in hearts from neonatal (7 days
      old) and adult (90 days old) Wistar rats. It was found that the release of NAD(+)
      from the perfused heart induced by I/R can be prevented by sanglifehrin A (SfA)
      only in the adult myocardium; SfA had no protective effect in the neonatal heart.
      Furthermore, the extent of Ca-induced swelling of mitochondria from neonatal rats
      was significantly lower than that from the adult animals; mitochondria from
      neonatal rats were more resistant at higher concentrations of calcium. In
      addition, not only the extent but also the rate of calcium-induced swelling was
      about twice higher in adult than in neonatal mitochondria. The results support
      the idea that lower sensitivity of the neonatal MPTP to opening may be involved
      in the mechanism of the higher tolerance of the neonatal heart to I/R injury.

PMID- 19756958
TI  - Advanced glycation endproducts alter functions and promote apoptosis in
      endothelial progenitor cells through receptor for advanced glycation endproducts
      mediate overpression of cell oxidant stress.
AB  - Endothelial progenitor cells (EPCs) play an important role in preventing
      atherosclerosis. The factors that regulate the function of EPCs are not
      completely clear. Increased formation of advanced glycation endproducts (AGEs) is
      generally regarded as one of the main mechanisms responsible for vascular damage
      in patients with diabetes and atherosclerosis. AGEs lead to the generation of
      reactive oxygen species (ROS) and part of the regenerative capacity of EPCs seems
      to be due to their low baseline ROS levels and reduced sensitivity to ROS-induced
      cell apoptosis. Therefore, we tested the hypothesis that AGEs can alter functions
      and promote apoptosis in EPCs through overpress cell oxidant stress. EPCs,
      isolated from bone marrow, were cultured in the absence or presence of AGEs (50,
      100, and 200 microg/ml). A modified Boyden's chamber was used to assess the
      migration of EPCs and the number of recultured EPCs was counted to measure the
      adhesiveness function. MTT assay was used to determine the proliferation
      function. ROS were analyzed using the ROS assay kit. A spectrophotometer was used
      to assess superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX)
      activity, and PCR was used to test mRNA expression of SOD and GSH-PX. SiRNA was
      used to block receptor for advanced glycation endproducts (RAGEs) expression.
      Apoptosis was evaluated by Annexin V immunostaining and TUNEL staining. Co
      culturing with AGEs increases ROS production, decreases anti-oxidant defenses,
      overpresses oxidant stress, inhibits the proliferation, migration, and adhesion
      of EPCs, and induces EPCs apoptosis. In addition, these effects were attenuated
      during block RAGE protein expression by siRNA. AGEs may serve to impair EPCs
      functions through RAGE-mediate oxidant stress, and promote EPCs sensitivity
      toward oxidative-stress-mediated apoptosis, which indicates a new
      pathophysiological mechanism of disturbed vascular adaptation in atherosclerosis
      and suggests that lower levels of AGEs might improve the success of progenitor
      cell therapy.

PMID- 19756959
TI  - Increased liver oxidative stress and altered PUFA metabolism precede development
      of non-alcoholic steatohepatitis in SREBP-1a transgenic spontaneously
      hypertensive rats with genetic predisposition to hepatic steatosis.
AB  - The temporal relationship of hepatic steatosis and changes in liver oxidative
      stress and fatty acid (FA) composition to the development of non-alcoholic
      steatohepatitis (NASH) remain to be clearly defined. Recently, we developed an
      experimental model of hepatic steatosis and NASH, the transgenic spontaneously
      hypertensive rat (SHR) that overexpresses a dominant positive form of the human
      SREBP-1a isoform in the liver. These rats are genetically predisposed to hepatic
      steatosis at a young age that ultimately progresses to NASH in older animals.
      Young transgenic SHR versus SHR controls exhibited simple hepatic steatosis which
      was associated with significantly increased hepatic levels of oxidative stress
      markers, conjugated dienes, and TBARS, with decreased levels of antioxidative
      enzymes and glutathione and lower concentrations of plasma alpha- and gamma
      tocopherol. Transgenic rats exhibited increased plasma levels of saturated FA,
      decreased levels of n-3 and n-6 polyunsaturated FA (PUFA), and increased n-6/n-3
      PUFA ratios. These results are consistent with the hypothesis that excess fat
      accumulation in the liver in association with increased oxidative stress and
      disturbances in the metabolism of saturated and unsaturated fatty acids may
      precede and contribute to the primary pathogenesis of NASH.

PMID- 19756960
TI  - Manganese superoxide dismutase: effect of the ala16val polymorphism on protein,
      activity, and mRNA levels in human breast cancer cell lines and stably
      transfected mouse embryonic fibroblasts.
AB  - The manganese superoxide dismutase (MnSOD) ala16val polymorphism has been
      associated with various diseases including breast cancer. In the present study,
      we investigated levels of MnSOD protein, enzymatic activity, and mRNA with
      respect to MnSOD genotype in several human breast carcinoma cell lines and in
      mouse embryonic fibroblasts (MEF), developed from the MnSOD knockout mouse,
      stably expressing human MnSOD-ala and MnSOD-val. In human breast cell lines, the
      MnSOD-ala allele was associated with increased levels of MnSOD protein and MnSOD
      protein per unit mRNA. In the MEF transformants, MnSOD activity correlated fairly
      well with MnSOD protein levels. MnSOD mRNA expression was significantly lower in
      MnSOD-ala versus MnSOD-val lines. MnSOD protein and activity levels were not
      related to MnSOD genotype in the transformed MEF, although, as observed in the
      human breast cell lines, the MEF human MnSOD-ala lines produced significantly
      more human MnSOD protein per unit mRNA than the human MnSOD-val lines. This
      suggests that there is more efficient production of MnSOD-ala protein compared to
      MnSOD-val protein. Examination of several indicators of reactive oxygen species
      levels, including superoxide and hydrogen peroxide, in wild-type MEF and in MEF
      expressing similar elevated amounts of MnSOD-ala or val activity did not show
      differences related to the levels of MnSOD protein expression. In conclusion, in
      both human breast carcinoma cell lines and MEF cell lines stably transfected with
      human MnSOD, the MnSOD-ala allele was associated with increased production of
      MnSOD protein per unit mRNA indicating a possible imbalance in MnSOD protein
      production from the MnSOD-val mRNA.

PMID- 19756961
TI  - The regulation of AMPK signaling in a natural state of profound metabolic rate
      depression.
AB  - In response to energy stress (and elevated AMP), the AMP-activated protein kinase
      (AMPK) coordinates the restoration of energy homeostasis. We determined that AMPK
      is activated in a model system (desert snail Otala lactea) during a physiological
      state of profound metabolic rate depression (estivation) in the absence of a rise
      in AMP. Kinetic characterization indicated a strong increase in AMPK activity and
      phosphorylation in estivation, consistent with an increase in P-Ser428 LKB, an
      established regulator of AMPK. Accordingly, approximately 2-fold increases in
      AMPKalpha1 protein and activity were observed with LKB1 immunoprecipitates from
      estivating snails. In vitro studies determined that AMPK in crude extracts was
      activated in the presence of cGMP and deactivated in conditions that permitted
      protein phosphatase type-2A (PP2A) activity. Furthermore, AMPKalpha1 protein and
      activity increased in PKG immunoprecipitates from estivating tissues, suggesting
      a novel role for PKG in the regulation of AMPK in vivo. We evaluated several
      downstream targets of AMPK. Acetyl-CoA carboxylase (ACC) activity was strongly
      inhibited in estivation, consistent with increased P-Ser79 content, and in vitro
      stimulation of AMPK negated citrate's ability to stimulate ACC aggregation.
      Analysis of other targets revealed a strong decrease in PPARgamma-coactivator
      1alpha expression in both tissues, which was related to decreased gluconeogenic
      protein expression in hepatic tissue, but no changes in mitochondrial biogenesis
      markers in muscle. We concluded that AMPK activation in O. lactea aids in
      facilitating the suppression of anabolic pathways, without necessarily activating
      ATP-generating catabolism.

PMID- 19756962
TI  - ST2 gene expression is proliferation-dependent and its ligand, IL-33, induces
      inflammatory reaction in endothelial cells.
AB  - ST2 gene products that are members of IL-1 receptor family are expressed in
      various cells such as growth-stimulated fibroblasts and Th2 helper T-cells, and
      recently, IL-33, which belongs to IL-1 family, was identified as the ligand for
      ST2L, the receptor type product of the ST2 gene. Subsequently, IL-33 and ST2L
      have been reported to be involved in Th2 immunity and inflammation, however,
      their functions on non-immunological cells are still obscure. Among non
      immunological adhesive cells, vascular endothelial cells were reported to express
      both ST2 gene products and IL-33, therefore, we investigated the expression
      manner of the ST2 gene in vascular endothelial cells and the effect of IL-33 on
      endothelial cells. ST2 gene was expressed in each of the vascular endothelial
      cell types tested, and the expression was growth-dependent and down-regulated
      when the cells were differentiated to form vascular structures on the
      extracellular membrane matrix. IL-33 scarcely affected the growth and tube
      formation of the endothelial cells, but induced IL-6 and IL-8 secretion from
      endothelial cells with the rapid activation of extracellular signal-regulated
      kinase (ERK) 1/2, so IL-33 is supposed to involve in inflammatory reaction of
      vascular endothelial cells through its receptor, ST2L.

PMID- 19756963
TI  - Rapid biomineralization of chitosan microparticles to apply in bone regeneration.
AB  - The aim of this study was to prepare bone like mineral (BLM) layers rapidly on
      the exterior surfaces of chitosan (CS) microparticles (MPs). The CS MPs were
      fabricated using a scale-up double emulsification method. The CS MPs were in the
      spherical shape and the size of 30-60 microm. The MPs were then placed in 5x
      concentrated simulated body fluid (5 x SBF) and allowed to undergo
      biomineralization to form a BLM layers on the surface of CS MPs at 37 degrees C
      over a 24 h period. The BML layers on the exterior surface of CS MPs were
      characterized using wide angle X-ray diffraction (XRD), Fourier transform
      infrared microscopy (FTIR), and scanning electron microscopy (SEM). Insulin like
      growth factor-1 (IGF-1) was dissolved at a concentration of 1 microg/ml in 5 x
      SBF to incorporate into the BLM layer. The CS MPs (100 mg) were incubated in a
      sample of 4 ml of 5 x SBF containing IGF-1 at a concentration of 1 microg/ml for
      24 h. The IGF-1 release from BML layers on CS MPs were studied by placing MPs in
      4 ml of phosphate buffered saline (PBS) and incubating MPs at 37 degrees C for 30
      days. Samples (100 microl) were taken over the course of the 30 days and analyzed
      using Enzyme-linked Immunosorbent assay (ELISA). The release IGF-1 from BML
      layers was in a burst manner followed by a sustained release during the 30-day
      period. This study suggests that the CS MPs have the potential to be used to help
      deliver therapeutic drugs to localized areas and hence increase and accelerate
      bone growth.

PMID- 19756964
TI  - Using small angle X-ray scattering to investigate the variation in composition
      across a graduated region within an intervertebral disc prosthesis.
AB  - The CAdisc-L is a polycarbonate urethane lumbar intervertebral disc prosthesis
      that aims to replicate the mechanical properties of a natural disc as closely as
      possible. In this work, Small Angle X-ray Scattering (SAXS) was used to
      investigate the variation in composition across prototype disc samples containing
      annulus and nucleus regions separated by a graduated region. An empirical data
      analysis method was developed involving the calculation of intensity ratios,
      since the SAXS data did not readily fit any of the standard analysis models.
      Calibration samples were used to quantify the variation in SAXS response with
      composition and a linescan method was employed to ascertain the change in
      composition across discs manufactured with different graduated region volumes.
      The graduated region width increases with the volume incorporated into it during
      manufacture, as expected, but the properties do not vary linearly across the
      graduated regions. The method developed during this work can be adapted for use
      with any series of polymer samples that shows a systematic variation in SAXS
      behaviour with composition.

PMID- 19756965
TI  - In vitro apatite formation on organic-inorganic hybrids in the CaO-SiO(2)-PO
      (5/2)-poly(tetramethylene oxide) system.
AB  - The osteoconduction potential of artificial materials is usually evaluated in
      vitro by apatite formation in a simulated body fluid (SBF) proposed by Kokubo and
      his colleagues. This paper reports the compositional dependence of apatite
      formation on organic-inorganic hybrids in the CaO-SiO(2)-PO(5/2)
      poly(tetramethylene oxide) system, initiated from tetraethoxysilane (TEOS),
      triethyl phosphate (OP(OEt)(3)), calcium chloride (CaCl(2)) and
      poly(tetramethylene oxide)(PTMO) modified with alkoxysilane. Formation of an
      apatite layer was observed on the surface of the organic-inorganic hybrids with
      molar ratios of TEOS/OP(OEt)(3) ranging from 100/0 to 20/80. The rate of apatite
      formation remarkably decreased when the hybrids were synthesized with
      TEOS/OP(OEt)(3) ratios of 40/60 or less. Hybrids without TEOS showed no apatite
      formation in SBF for up to 14 days. Addition of small amounts of OP(OEt)(3) to
      TEOS in the hybrids led to the high dissolution of calcium and silicate, while
      addition of large amounts of OP(OEt)(3) decreased the dissolution of calcium and
      silicate ions and resulted in reduced apatite formation regardless of the
      dissolution of phosphate ions from the hybrids.

PMID- 19756966
TI  - Spray-spinning: a novel method for making alginate/chitosan fibrous scaffold.
AB  - The subject of our investigations was the process of obtaining alginate/chitosan
      polyelectrolyte complex (PEC) fibers. In this study, a novel method named "spray
      spinning" was developed for the making of these hybrid fibers. In spray-spinning,
      a chitosan solution was sprayed into a flowing sodium alginate solution and
      sheared into streamlines. The elongated streamlines subsequently transformed into
      alginate/chitosan PEC fibers. Average diameter of the fibers increased with the
      increasing of chitosan concentration used in spinning. The fibers showed a high
      water-absorbability of about 45 folds of water to their dry weight and retained
      their integrity after incubation in Minimum Essential Medium (MEM) for up to 30
      days. In vitro co-culture experiments indicated that the fibers could support the
      three-dimensional growth of HepG2 cells and did not display any cyto-toxicity.
      Moreover, in vivo implanting experiments indicated that the connective tissue
      cells infiltrated into the implanted fibrous scaffolds in 3 weeks after surgery.
      These results demonstrated the potential applications of the as-spun fibers in
      regenerative medicine and tissue engineering.

PMID- 19756967
TI  - Influence of dynamic load on friction behavior of human articular cartilage,
      stainless steel and polyvinyl alcohol hydrogel as artificial cartilage.
AB  - Many biomaterials are being developed to be used for cartilage substitution and
      hemiarthroplasty implants. The lubrication property is a key feature of the
      artificial cartilage. The frictional behavior of human articular cartilage,
      stainless steel and polyvinyl alcohol (PVA) hydrogel were investigated under
      cartilage-on-PVA hydrogel contact, cartilage-on-cartilage contact and cartilage
      on-stainless steel contact using pin-on-plate method. Tests under static load,
      cyclic load and 1 min load change were used to evaluate friction variations in
      reciprocating motion. The results showed that the lubrication property of
      cartilage-on-PVA hydrogel contact and cartilage-on-stainless steel contact were
      restored in both 1 min load change and cyclic load tests. The friction
      coefficient of PVA hydrogel decreased from 0.178 to 0.076 in 60 min, which was
      almost one-third of the value under static load in continuous sliding tests. In
      each test, the friction coefficient of cartilage-on-cartilage contact maintained
      far lower value than other contacts. It is indicated that a key feature of
      artificial cartilage is the biphasic lubrication properties.

PMID- 19756968
TI  - In vitro and in vivo evaluation of the effects of demineralized bone  matrix or
      calcium sulfate addition to polycaprolactone-bioglass  composites.
AB  - The objective of this study was to improve the efficacy of
      polycaprolactone/bioglass (PCL/BG) bone substitute using demineralized bone
      matrix (DBM) or calcium sulfate (CS) as a third component. Composite discs
      involving either DBM or CS were prepared by compression moulding. Bioactivity of
      discs was evaluated by energy dispersive X-ray spectroscopy (ESCA) and scanning
      electron microscopy (SEM) following simulated body fluid incubation. The closest
      Calcium/Phosphate ratio to that of hydroxyl carbonate apatite crystals was
      observed for PCL/ BG/DBM group (1.53) after 15 day incubation. Addition of
      fillers increased microhardness and compressive modulus of discs. However, after
      4 and 6-week PBS incubations, PCL/BG/DBM discs showed significant decrease in
      modulus (from 266.23 to 54.04 and 33.45 MPa, respectively) in parallel with its
      highest water uptakes (36.3 and 34.7%). Discs preserved their integrity with only
      considerable weight loss (7.5-14.5%) in PCL/BG/DBM group. In vitro cytotoxicity
      tests showed that all discs were biocompatible.

PMID- 19756969
TI  - Structural properties of polysaccharide-based microcapsules  for soft tissue
      regeneration.
AB  - Autologous and eterologous cell encapsulation has been extensively studied for
      clinical application in functional organs substitution, recombinant cell
      transplantation in gene therapy or in muscle and cartilage regeneration to treat
      degenerative pathologies. In this work, calcium alginate, calcium
      alginate/chitosan, calcium alginate/gelatin and pectin/chitosan microcapsules
      were prepared to be used as innovative injectable scaffolds for soft issue
      regeneration by a simple extrusion method from aqueous solutions. Prepared
      microcapsules had spherical morphology, whereas their size was deeply influenced
      by the polymeric composition. When incubated in a physiological-like environment
      up to 30 days, they underwent an initial swelling, followed by weight loss at
      different rates, depending on the microcapsules formulation. The encapsulation of
      mouse myoblast cells (C2C12 cell line) was obtained in calcium alginate, calcium
      alginate/chitosan, calcium alginate/gelatin microcapsules. Cells were alive
      throughout the encapsulation procedure, and were recovered by a mechanical
      rupture of the microcapsules. After 7 days, fractured microcapsules led cells to
      migrate gradually out.

PMID- 19756970
TI  - Structural and compositional features of amorphous calcium  phosphate at the
      early stage of precipitation.
AB  - Precipitates formed at an early stage (during the first 6 h) of the
      hydroxyapatite crystallization of a solution were studied. A nitrous synthesis
      was used (0.583M (NH(4))(2)HPO(4) and 0.35 M Ca(NO(3))(2).4H(2)O solutions at pH
      11-12, 21 degrees C, fast mixing, lyophilization of aliquots). Although XRD
      patterns indicated an amorphous calcium phosphate (ACP), IR spectra revealed
      apatite nanocrystals in the precipitates. Some amount of free calcium was found
      in the mother solution by mass spectrometrical analysis of the aliquots. This
      amount considerably decreased as the synthesis proceeded, however, the decrease
      had a slight effect on the crystallinity of the precipitates. A new suggestion on
      the nature of delayed crystallization (under conditions as those in the present
      study) was proposed. The free calcium adsorbed by the nanoparticles from the
      solution formed a shell around a particle because the calcium diffusion into the
      bulk was poor at the low synthesis temperature. As such, the encapsulation
      delayed the crystallization of the nanoparticles. Evidence for this suggestion
      was given. New possibilities were proposed for preparation of bioactive materials
      of desired composition based on the structural and compositional peculiarities of
      the X-ray diffraction-amorphous calcium phosphates.

PMID- 19756971
TI  - In vitro evaluation of the PEtU-PDMS material  immunocompatibility: the influence
      of surface  topography and PDMS content.
AB  - The aim of the present work is to evaluate the in vitro immunocompatibility of an
      elastomeric material with feasible applications in the cardiovascular field. In
      particular, since it is well known that surface chemistry and topography play a
      key role in the foreign body response, their influence on human monocytes was
      evaluated. The material, constituted by a poly(ether)urethane (PEtU) and a
      polydimethylsiloxane (PDMS), was synthesized to manufacture films and small
      diameter vascular grafts with three different surface topographical features,
      smooth, rough and porous, and siloxane rates, 10, 30 and 40. Human THP-1
      monocytes have been cultured for 72 h on the films and human blood has been
      circulating for 2 h into the grafts to assess leukocyte adhesion and cytokine
      releases. Materials extracts were utilized to evaluate monocyte apoptosis. Smooth
      films showed lower cell adhesion degrees than rough and porous ones. All the PEtU
      PDMS (poly(ether)urethane-polydimethylsiloxane) films and vascular grafts induced
      a narrow inflammatory response, as demonstrated by slight cytokine secretion
      levels, in particular samples with the highest PDMS contents (30 and 40%) induced
      the lowest IL-1b secretion. Moreover, an absence of monocyte apoptosis advises
      that the negligible release values have not to be ascribed to material toxicity.
      In the end, surface topography showed to affect only monocyte adhesion while
      siloxane content the cytokine release. Therefore, the possibility to modify the
      above tested parameters during material synthesis and manufacture could allow to
      bound the inflammatory potency of the PEtU-PDMS devices and render them excellent
      candidates for cardiovascular reconstruction.

PMID- 19756972
TI  - Microneedle arrays allow lower microbial penetration than hypodermic needles in
      vitro.
AB  - METHODS: In this study we determined, for the first time, the ability of
      microorganisms to traverse microneedle-induced holes using two different in vitro
      models. RESULTS: When employing Silescol membranes, the numbers of Candida
      albicans, Pseudomonas aeruginosa and Staphylococcus epidermidis crossing the
      membranes were an order of magnitude lower when the membranes were punctured by
      microneedles rather than a 21G hypodermic needle. Apart from the movement of C.
      albicans across hypodermic needle-punctured membranes, where 40.2% of the
      microbial load on control membranes permeated the barrier over 24 h, the numbers
      of permeating microorganisms was less than 5% of the original microbial load on
      control membranes. Experiments employing excised porcine skin and radiolabelled
      microorganisms showed that the numbers of microorganisms penetrating skin beyond
      the stratum corneum were approximately an order of magnitude greater than the
      numbers crossing Silescol membranes in the corresponding experiments.
      Approximately 10(3) cfu of each microorganism adhered to hypodermic needles
      during insertion. The numbers of microorganisms adhering to MN arrays were an
      order of magnitude higher in each case. CONCLUSION: We have shown here that
      microneedle puncture resulted in significantly less microbial penetration than
      did hypodermic needle puncture and that no microorganisms crossed the viable
      epidermis in microneedle-punctured skin, in contrast to needle-punctured skin.
      Given the antimicrobial properties of skin, it is, therefore, likely that
      application of microneedle arrays to skin in an appropriate manner would not
      cause either local or systemic infection in normal circumstances in immune
      competent patients. In supporting widespread clinical use of microneedle-based
      delivery systems, appropriate animal studies are now needed to conclusively
      demonstrate this in vivo. Safety in patients will be enhanced by aseptic or
      sterile manufacture and by fabricating microneedles from self-disabling materials
      (e.g. dissolving or biodegradable polymers) to prevent inappropriate or
      accidental reuse.

PMID- 19756973
TI  - Pharmacokinetics and efficacy of a biweekly dosage formulation of exenatide in
      Zucker diabetic fatty (ZDF) rats.
AB  - PURPOSE: To develop an improved sustained-release (SR) formulation of exenatide
      (a therapy for patients with type 2 diabetes mellitus) in a biweekly dosage form
      with therapeutic efficacy comparable to that achieved with twice-daily injections
      of the drug. METHODS: A SR formulation of exenatide, DA-3091, was prepared by
      single-emulsion solvent evaporation using poly(D,L-lactide-co-glycolide). Plasma
      exenatide, as well as plasma insulin, non-fasting blood glucose and HbA1c
      concentrations, and changes in food intake and body weight were evaluated in both
      Zucker diabetic fatty (ZDF) and ZDF lean control rats. RESULTS: After a single SC
      administration of DA-3091 (i.e., 2 mg/kg of exenatide), the plasma exenatide
      concentration increased and remained elevated in both groups. The concentrations
      of non-fasting blood glucose and HbA1c decreased significantly following a single
      SC injection of DA-3091 only in ZDF rats, indicating that the effects of
      exenatide are dependent on blood glucose concentration. On the other hand, both
      food intake and body weight gain were reduced in ZDF and ZDF lean control rats. A
      single injection of DA-3091 (i.e., 2 mg/kg of exenatide) lowered non-fasting
      blood glucose and HbA1c concentrations more effectively than 14 days of twice
      daily administration of exenatide (i.e., 1.96 mg/kg of exenatide). CONCLUSION: DA
      3091 has the potential to be used safely and efficaciously in a biweekly dosing
      regimen.

PMID- 19756974
TI  - PLGA nanoparticles stabilized with cationic surfactant: safety studies and
      application in oral delivery of paclitaxel to treat chemical-induced breast
      cancer in rat.
AB  - PURPOSE: This study was carried out to formulate poly(lactide-co-glycolide)
      (PLGA) nanoparticles using a quaternary ammonium salt didodecyl dimethylammonium
      bromide (DMAB) and checking their utility to deliver paclitaxel by oral route.
      METHODS: Particles were prepared by emulsion solvent diffusion evaporation
      method. DMAB and particles stabilized with it were evaluated by MTT and LDH
      cytotoxicity assays. Paclitaxel was encapsulated in these nanoparticles and
      evaluated in a chemical carcinogenesis model in Sprague Dawley rats. RESULTS: MTT
      and LDH assays showed the surfactant to be safe to in vitro cell cultures at
      concentrations <33 microM. PLGA nanoparticles prepared using this stabilizer were
      also found to be non-toxic to cell lines for the duration of the study. When
      administered orally to rats bearing chemically induced breast cancer,
      nanoparticles were equally effective/better than intravenous paclitaxel in
      cremophor EL at 50% lower dose. CONCLUSIONS: This study proves the safety and
      utility of DMAB in stabilizing preformed polymers like PLGA resulting in
      nanoparticles. This preliminary data provides a proof of concept of enabling oral
      chemotherapy by efficacy enhancement for paclitaxel.

PMID- 19756975
TI  - At the biological modeling and simulation frontier.
AB  - We provide a rationale for and describe examples of synthetic modeling and
      simulation (M&S) of biological systems. We explain how synthetic methods are
      distinct from familiar inductive methods. Synthetic M&S is a means to better
      understand the mechanisms that generate normal and disease-related phenomena
      observed in research, and how compounds of interest interact with them to alter
      phenomena. An objective is to build better, working hypotheses of plausible
      mechanisms. A synthetic model is an extant hypothesis: execution produces an
      observable mechanism and phenomena. Mobile objects representing compounds carry
      information enabling components to distinguish between them and react accordingly
      when different compounds are studied simultaneously. We argue that the familiar
      inductive approaches contribute to the general inefficiencies being experienced
      by pharmaceutical R&D, and that use of synthetic approaches accelerates and
      improves R&D decision-making and thus the drug development process. A reason is
      that synthetic models encourage and facilitate abductive scientific reasoning, a
      primary means of knowledge creation and creative cognition. When synthetic models
      are executed, we observe different aspects of knowledge in action from different
      perspectives. These models can be tuned to reflect differences in experimental
      conditions and individuals, making translational research more concrete while
      moving us closer to personalized medicine.

PMID- 19756976
TI  - Multivariate analysis of the sequence dependence of asparagine deamidation rates
      in peptides.
AB  - PURPOSE: To develop a quantitative scheme to describe and predict asparagine
      deamidation in polypeptides using chemometric models employing reduced
      physicochemical property scales of amino acids. METHODS: Deamidation rates for
      306 pentapeptides, Gly-(n-1)-Asn-(n+1)-Gly, with the residues n-1 and n+1 varying
      over the naturally occurring amino acids, were obtained from literature. A
      multivariate regression technique, called projection to latent structures (PLS),
      was used to establish mathematical relationships between the physicochemical
      properties and the deamidation half-lives of the amino acid sequences. Three
      reduced physicochemical property scales, amide hydrogen exchange rates (to
      describe the relative acidity of the amide protons) and flexibility parameters
      for the sequences were evaluated for their predictive capacity. RESULTS: The most
      effective descriptors of the deamidation half-lives were reduced-property
      parameters for amino acids called zz-scores. The PLS models with the reduced
      property scales, combined with the hydrogen exchange rates and/or flexibility
      parameters, explained more than 95% of the sequence-dependent variation in the
      deamidation half-lives. The amide hydrogen exchange rate (i.e., amide proton
      acidity), hydrophilicity, polarizability, and size of amino acids in position n+1
      were found to be the principal factors governing the rate of deamidation. The
      effect of amino acids in position n-1 was found to be negligible. CONCLUSIONS:
      Chemometric analysis employing reduced physicochemical parameters can provide an
      accurate prediction of chemical instability in peptides and proteins. The
      relative importance of these various factors could also be determined.

PMID- 19756977
TI  - Use of the Behavioral Assessment System for Children 2nd Edition: Parent Report
      Scale in pediatric cancer populations.
AB  - This study examined the use of the Behavioral Assessment System for Children-2nd
      Edition: Parent Report Scale (BASC-2; Reynolds & Kamphaus, Behavior assessment
      system for children, 2004) in a pediatric cancer population. Comparisons of scale
      scores were made between pediatric cancer participants and controls. Within group
      comparisons were also made between subtypes of pediatric cancer. Parents of 111
      children and adolescents who had experienced pediatric cancer completed the BASC
      2 as part of larger studies of parent-child adjustment to cancer. Scores on the
      BASC-2 for cancer survivors were compared to a matched control group. Results
      from MANOVA analyses revealed that children with cancer were categorized as
      evidencing more emotional and cognitive complaints compared to the control
      children. Notably, no significant within group differences emerged on the
      subscales with regard to cancer subtype. Although preliminary, these results
      suggest that the BASC-2 can identify the cognitive and emotional differences
      between cancer survivors and controls.

PMID- 19756978
TI  - Government sanctioned "tight" and "loose" slot machines: how having multiple
      versions of the same slot machine game may impact problem gambling.
AB  - In Ontario, Canada, the regulator approves identical looking slot machine games
      with different payback percentages. We gained access to the design documents
      (called PAR Sheets) used to program these different versions of the same slots
      game and ran Gambler's Ruin simulations of 2,000 first-time players who each
      arrived with a $100 bankroll and played either the 85 or 98% version of the same
      game until broke. Simulations revealed that the typical (median) player's
      experience did not differ significantly between versions. However the payback
      percentage affected the experience of players in the upper tails of the
      distributions with those in the 98% version having dramatically more total spins,
      winning spins, entries into the "bonus mode", and "hand pays" (a win of $125 or
      more on a given spin). Most importantly, the number of simulated players who had
      a maximum peak balance in excess of $1,000 rose tenfold-from 5 in the 85% version
      to 54 in the 98% version. The results are discussed in terms of the Pathways
      Model of Problem and Pathological Gambling especially in terms of behavioural
      conditioning, cognitive beliefs, and early big wins. It may well be that those
      machines that are on the surface the "fairest" to the gambler, actually pose the
      most risk for ensuing gambling problems.

PMID- 19756979
TI  - The convergence of gambling and digital media: implications for gambling in young
      people.
AB  - Adolescents' use of the Internet and other digital media for the purpose of
      gambling represents a serious concern in modern society. This paper overviews
      some of the available monetary and non-monetary forms of gambling within new
      digital and online media and monetary forms of games with gambling-like
      experiences. With reference to current psychological knowledge on the risk
      factors that promote adolescent gambling, it is suggested that new gambling
      technologies may: (a) make gambling more accessible and attractive to young
      people, (b) may promote factually incorrect information about gambling, (c)
      provide an easy escape from real world problems such as depression and social
      isolation, (d) create a gambling environment that easily facilitates peer
      pressures to gamble, (e) ease parental transmission of gambling attitudes and
      beliefs, and (f) make gambling more ubiquitous and socially acceptable. The
      unique risks of Internet gambling for young people are critically discussed, as
      well as the lack of restricted classification for video games and other media
      that feature interactive, non-monetary forms of gambling.

PMID- 19756980
TI  - Analysis of PK/PD risk factors for development of type 2 diabetes in high risk
      population using Bayesian analysis of glucose-insulin kinetics.
AB  - This study was designed to investigate the pharmacokinetics/pharmacodynamics
      (PK/PD) risk factors preceding the onset of type 2 diabetes using a population
      based Bayesian nonlinear hierarchical model to describe the glucose-insulin
      kinetics. One hundred fifty-two healthy subjects with a family history of type 2
      diabetes were recruited. Each subject received an intravenous glucose tolerance
      test (IVGTT) and the data of glucose and insulin was collected when entering the
      study. After the test, subjects were followed up to 25 years and further divided
      into the diabetic outcome group and non-diabetic outcome group according to the
      follow-up results. A glucose-insulin kinetic model was developed to account for
      the physiology and molecular biology of the insulin biphasic secretion and
      glucose-insulin interactions with a minimal structure. The population PK/PD
      parameters of the two groups were estimated from the proposed glucose-insulin
      kinetic model. The relationships between the population PK/PD parameters and the
      diabetic follow-up results were evaluated. A high insulin baseline concentration,
      a lower maximum insulin-dependent glucose removal and a lower insulin removal
      rate constant were found associated with the development of type 2 diabetes in
      the high risk population. The study shows that the very early pre-diabetic
      pharmacokinetic differences exist and can be helpful for prediction of
      development of type 2 diabetes.

PMID- 19756981
TI  - Excited state absorption study in hematoporphyrin IX.
AB  - We present the study of the excited state absorption of Hematoporphyrin IX
      dissolved in dimethyl sulfoxide. All measurements were carried out using open
      aperture Z-scan and white-light continuum pump-probe with picosecond pulses to
      avoid triplet excited state absorption. Without the latter contribution, the
      results obtained with both techniques show a transition to a high singlet excited
      state. The vibronic progression of the Q-band is observed due to photobleaching
      of the ground state. In addition, we show that the excited state presents reverse
      saturable absorption for most of the spectral range studied. A long relaxation
      component of the first singlet excited state was evidenced with the pump-probe
      experiment. This result is in agreement with fluorescence lifetime and
      fluorescence quantum yield measurements. In order to elucidate the origin of the
      nonlinear effects, we used a three-level energy diagram to describe the principal
      singlet-singlet transitions.

PMID- 19756982
TI  - Effective critical micellar concentration of a zwitterionic detergent: a
      fluorimetric study on n-dodecyl phosphocholine.
AB  - We have investigated the effect of ionic strength on the aggregation behavior of
      n-dodecyl phosphocholine. On the basis of the classical Corrin-Harkins relation,
      the critical micellar concentration of this detergent decreases with a biphasic
      trend on lithium chloride addition. It is nearly constant below 150 mM salt, with
      a mean value of 0.91 mM, whereas it undergoes a dramatic 80-fold decrease in 7 M
      LiCl. Such a drop in the critical micellar concentration could be explained by
      the effect of salting out and the implication of phosphocholine head groups on
      the organization of surrounding water. Knowledge of the effective critical
      micellar concentration of n-dodecyl phosphocholine could be useful in the
      purification of membrane proteins in non-denaturing conditions.

PMID- 19756983
TI  - Synthesis and characterization of oxazine-doped silica nanoparticles for their
      potential use as stable fluorescent reagents.
AB  - The synthesis process to obtain silica nanoparticles (NPs) doped with two oxazine
      dyes, nile blue and cresyl violet, has been investigated using a modification of
      the reverse micelle microemulsion method and a procedure based on the Stober
      method. A micellar medium provided by the non-ionic surfactant Triton X-100 in a
      hexanol:water mixture and an ethanol:water mixture, have been used to provide the
      synthesis medium in each case. Tetraethoxysilane has been used as the initiator
      of the polymerization and condensation reactions after its hydrolysis in basic
      medium using ammonium hydroxide. Dye-silane precursor NPs have been also
      synthesized in order to compare their potential advantages against the NPs
      obtained by the direct encapsulation of the oxazine dyes. Size distribution and
      fluorescence of the synthesized NPs, which were monitored using Transmision
      Electron Microscopy (TEM) and a microplate reader, respectively, depend on the
      molar ratio and total concentration of the reagents involved in the synthesis.
      NPs obtained using the developed synthesis procedures had sizes below 400 nm in
      most instances and the best luminescent properties were observed for NPs with
      sizes ranging from 100 to 300 nm. Lower sizes result in a decrease in the
      fluorescence intensities of these nanomaterials. Parameters related with the
      luminescence features of these NPs were calculated in order to compare the
      feasibility of both synthesis approaches. The repeatability of the reverse
      micelle microemulsion procedure performed in different days gave a relative
      standard deviation of 10% for the fluorescence intensity values.

PMID- 19756984
TI  - Introduction--drinking deep: a tribute to John Stone.

PMID- 19756985
TI  - Medical education and disability studies.
AB  - The biomedicalist conceptualization of disablement as a personal medical tragedy
      has been criticized by disability studies scholars for discounting the difference
      between disability and impairment and the ways disability is produced by socio
      environmental factors. This paper discusses prospects for partnerships between
      disability studies teaching/research and medical education; addresses some of the
      themes around the necessity of critical disability studies training for medical
      students; and examines a selection of issues and themes that have arisen from
      disability education courses within medical schools globally. The paper concludes
      that providing there is a commitment from senior management, universities are
      well positioned to apply both vertical and horizontal approaches to teaching
      disability studies to medical students.

PMID- 19756986
TI  - Association of interferon-gamma gene polymorphisms in Taiwanese children with
      biliary atresia.
AB  - BACKGROUND: Biliary atresia (BA) is a devastating neonatal hepatobiliary disease
      characterized by bile duct inflammation and fibrosis. The pathogenesis remains
      unclear, but immunologically mediated injury to bile ducts following an
      infectious insult is likely to play a critical role. Interferon-gamma (IFN-gamma)
      is a key cytokine that affects immune-mediated inflammatory responses. OBJECTIVE:
      This study aims to investigate whether polymorphisms of the IFN-gamma (IFNG) gene
      were associated with susceptibility to BA. METHODS: The IFNG -1615 C/T, -183 G/T,
      +874 A/T, and +2197 A/G polymorphisms were genotyped using the TaqMan assay, and
      CA repeat microsatellite was analyzed using capillary electrophoresis in 50
      children with BA and 788 ethnically matched healthy controls. RESULTS: The
      distribution of genotype, allele, and haplotype frequencies of these IFNG gene
      variants did not differ significantly between children with BA and controls.
      CONCLUSION: Polymorphisms of the IFNG gene do not appear to play a major role in
      the genetic predisposition to BA in Taiwanese children.

PMID- 19756987
TI  - Implication of Th17 and Th1 cells in patients with chronic active hepatitis B.
AB  - OBJECTIVE: The pathogenesis of hepatitis B virus (HBV)-associated chronic liver
      disease is still not fully understood. The immune imbalance of cytokine profile
      exerts a profound influence on the resolution of HBV infections and HBV
      clearance. This present study aimed to evaluate the immune status of the
      peripheral T helper (Th) 17 and Th1 cells in the active patients with chronic HBV
      infection. MATERIALS AND METHODS: Thirty patients with chronic active hepatitis B
      were included in our present study. The frequency of peripheral Th 17 cells
      (CD3(+)CD8(-)IL-17(+) T cells), Th1 cells (CD3(+)CD8(-)IFN-gamma(+) T cells), and
      Tc1 cells (CD3(+)CD8(+)IFN-gamma(+) T cells) in chronic hepatitis B (CHB) were
      analyzed by flow cytometry. The protein and mRNA levels of interleukin-17 (IL-17)
      and interferon-gamma (IFN-gamma) were measured by enzyme-linked immunosorbent
      assay and quantitative real-time polymerase chain reaction (PCR). RESULTS: The
      percentage of Th17 cells in peripheral blood of CHB patients (1.53 +/- 0.52%) was
      significantly increased than that in normal controls (0.92 +/- 0.20%; P < 0.05).
      In contrast, the percentage of Th1 and Tc1 cells of CHB patients was
      significantly decreased as compared with that of control group. The frequency of
      Th17 cells had a negative correlation with Th1 cells, and a positive correlation
      with serum alanine aminotransferase in CHB patients. CONCLUSION: The elevated
      peripheral Th17 cells were obtained in the patient with chronic active hepatitis
      B, suggesting its potential role in the immune activation of chronic HBV
      infection.

PMID- 19756988
TI  - A new model of induced experimental systemic lupus erythematosus (SLE) in pigs
      and its amelioration by treatment with a tolerogenic peptide.
AB  - INTRODUCTION: Systemic lupus erythematosus (SLE) is characterized by a variety of
      autoantibodies and systemic clinical manifestations. A tolerogenic peptide,
      hCDR1, ameliorated lupus manifestations in mice models. The objectives of this
      study were to induce experimental SLE in pigs and to determine the ability of
      hCDR1 to immunomodulate the disease manifestations. RESULTS AND DISCUSSION: We
      report here the successful induction, by a monoclonal anti-DNA antibody, of an
      SLE-like disease in pigs, manifested by autoantibody production and glomerular
      immune complex deposits. Treatment of pigs with hCDR1 ameliorated the lupus
      related manifestations. Furthermore, the treatment downregulated the gene
      expression of the pathogenic cytokines, interleukin (IL)-1beta, tumor necrosis
      factor alpha, interferon gamma, and IL-10, and upregulated the expression of the
      immunosuppressive cytokine transforming growth factor beta, the antiapoptotic
      molecule Bcl-xL, and the suppressive master gene, Foxp3, hence restoring the
      expression of the latter to normal levels. Thus, hCDR1 is capable of ameliorating
      lupus in large animals and is a potential candidate for the treatment of SLE
      patients.

PMID- 19756989
TI  - Oral administration of OKT3 monoclonal antibody to human subjects induces a dose
      dependent immunologic effect in T cells and dendritic cells.
AB  - INTRODUCTION: Parenteral OKT3 is used to treat transplant rejection and a
      humanized anti-CD3 Mab has shown positive clinical effects in new onset diabetes.
      Oral administration of anti-CD3 has not been tested in humans, but suppresses
      autoimmunity in animal models. Beta-glucosylceramide enhances NKT cell and
      regulatory T cell activity and enhances the effects of oral anti-CD3 in animals.
      MATERIALS AND METHODS: Fifteen healthy volunteers (three per group) received
      orally administered OKT3 over a dose range of 0.2 to 5.0 mg daily with or without
      beta-glucosylceramide 7.5 mg for 5 days. Safety and immune parameters were
      measured on days 5, 10, and 30. RESULTS AND DISCUSSION: Oral OKT3 enhanced T cell
      proliferation, suppressed Th1 and Th17 responses by 43% and 41%, respectively,
      increased TGF-beta/IL-10 expression and decreased IL-23/IL-6 expression by
      dendritic cells, and affected the IgG repertoire as measured by antigen arrays.
      Co-administration of oral beta-glucosylceramide induced similar effects. No side
      effects were observed and no subjects developed human anti-mouse antibodies.
      CONCLUSION: These findings demonstrate that oral anti-CD3 monoclonal antibody is
      safe and biologically active in humans and presents a new avenue for the
      treatment of autoimmune diseases.

PMID- 19756990
TI  - Activation profile of intracellular mitogen-activated protein kinases in
      peripheral lymphocytes of patients with systemic lupus erythematosus.
AB  - INTRODUCTION: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease
      associated with aberrant activation of T and B lymphocytes. Abnormal activation
      of intracellular signaling molecules in lymphocytes by inflammatory cytokines can
      instigate the inflammation in SLE. MATERIALS AND METHODS: The activation of
      extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK) and
      p38 mitogen-activated protein kinase (MAPK) in inflammatory cytokine IL-18
      activated monocytes, CD4+ T helper (Th) lymphocytes, CD8+ T lymphocytes, and
      CD19+ B lymphocytes in 22 SLE patients and 20 sex- and age-matched control
      subjects were measured by flow cytometry. RESULTS AND DISCUSSION: The basal
      expressions of phospho-p38 MAPK in CD4+ T lymphocytes, CD8+ T lymphocytes, and B
      lymphocytes were significantly higher in SLE patients than controls (all p<0.05).
      The expression of phospho-p38 MAPK in CD4+ T lymphocytes, CD8+ T lymphocytes and
      B lymphocytes, and phospho-JNK in CD8+ T lymphocytes and B lymphocytes was also
      significantly elevated in SLE patients upon the activation by IL-18, exhibiting
      significant correlation with the plasma concentrations of Th1 chemokine CXCL10
      (all p<0.05). The expression of phospho-JNK in IL-18 activated CD8+ T lymphocytes
      and the relative % fold increase of the expression of phospho-JNK upon IL-18
      activation in B lymphocytes were significantly correlated with SLE disease
      activity index (both p<0.05). CONCLUSION: The inflammation-mediated activation of
      JNK and p38 MAPK signaling pathways in T and B lymphocytes can be the underlying
      intracellular mechanisms causing lymphocyte hyperactivity in SLE.

PMID- 19756991
TI  - Quantitative proteomic analysis of CMS-related changes in Honglian CMS rice
      anther.
AB  - Honglian (HL) cytoplasmic male sterility (CMS) is one of the rice CMS types and
      has been widely used in hybrid rice production in China. The CMS line (Yuetai A,
      YTA) has a Yuetai B (maintainer line, YTB) nuclear genome, but has a rearranged
      mitochondrial (mt) genome consisting of Yuetai B. The fertility of hybrid (HL-6)
      was restored by restorer gene in nuclear genome of restorer line (9311). We used
      isotope-code affinity tag (ICAT) technology to perform the protein profiling of
      uninucleate stage rice anther and identify the CMS-HL related proteins. Two
      separate ICAT analyses were performed in this study: (1) anthers from YTA versus
      anthers from YTB, and (2) anthers from YTA versus anthers from HL-6. Based on the
      two analyses, a total of 97 unique proteins were identified and quantified in
      uninucleate stage rice anther under the error rate of less than 10%, of which
      eight proteins showed abundance changes of at least twofold between YTA and YTB.
      Triosephosphate isomerase, fructokinase II, DNA-binding protein GBP16 and
      ribosomal protein L3B were over-expressed in YTB, while oligopeptide transporter,
      floral organ regulator 1, kinase and S-adenosyl-L: -methionine synthetase were
      over-expressed in YTA. Reduction of the proteins associated with energy
      production and lesser ATP equivalents detected in CMS anther indicated that the
      low level of energy production played an important role in inducing CMS-HL.

PMID- 19756992
TI  - Preventing non-suicidal self-injury in adolescents: the signs of self-injury
      program.
AB  - Non-suicidal self-injury (NSSI) continues to be a problem among youth and there
      is a great need for programming aimed at reducing NSSI in adolescents. The signs
      of self-injury program is the first known NSSI school-based prevention program
      for adolescents that attempts to increase knowledge, improve help-seeking
      attitudes and behaviors, and decrease acts of NSSI. A total of five schools
      implemented the program in selected classrooms (n = 274 adolescents; 51.5%
      female, mean age = 16.07 years) that consisted of predominantly Caucasian (73%)
      adolescents. Researchers collected pre-post evaluation surveys of the program and
      feasibility interviews were conducted with the school guidance personnel who ran
      the program. Results indicated the prevention program did not produce iatrogenic
      effects, increased accurate knowledge and improved help-seeking attitudes and
      intentions among students. No significant changes were found in regards to self
      reported formal help-seeking actions. Feasibility responses indicate the program
      is user-friendly and well received by school personnel. The data offer
      preliminary evidence that the program may be an effective prevention program for
      schools.

PMID- 19756994
TI  - Participating in sport and music activities in adolescence: the role of activity
      participation and motivational beliefs during elementary school.
AB  - This investigation examined the precursors of adolescents' participation in sport
      and music activities in the United States by testing a developmental model across
      7 years. Data were drawn from youth questionnaires in the Childhood and Beyond
      Study (92% European American; N = 594). Findings suggest that patterns of
      participation across a 3-year period in elementary school predict adolescents'
      participation through their motivational beliefs. Specifically, children who
      participated in an activity, children who participated consistently across
      multiple years, and children who were highly active had higher adolescent
      motivational beliefs 4 years later than their peers. These motivational beliefs,
      in turn, positively predicted adolescents' participation 1 year later. Cross
      domain analyses suggest that children typically maintain their orientation toward
      sports and music (e.g., high music-low sport orientation, not oriented toward
      either domain) as they age. These findings highlight the consistency in
      children's leisure pursuits and interests from childhood through adolescence.

PMID- 19756995
TI  - Variable-centered and person-centered approaches to studying Mexican-origin
      mother-daughter cultural orientation dissonance.
AB  - The overall aim of the current study was to identify the methodological approach
      and corresponding analytic procedure that best elucidated the associations among
      Mexican-origin mother-daughter cultural orientation dissonance, family
      functioning, and adolescent adjustment. To do so, we employed, and compared, two
      methodological approaches (i.e., variable-centered and person-centered) via four
      analytic procedures (i.e., difference score, interactive, matched/mismatched
      grouping, and latent profiles). The sample consisted of 319 girls in the 7th or
      10th grade and their mother or mother figure from a large Southwestern,
      metropolitan area in the US. Family factors were found to be important predictors
      of adolescent adjustment in all models. Although some findings were similar
      across all models, overall, findings suggested that the latent profile procedure
      best elucidated the associations among the variables examined in this study. In
      addition, associations were present across early and middle adolescents, with a
      few findings being only present for one group. Implications for using these
      analytic procedures in studying cultural and family processes are discussed.

PMID- 19756996
TI  - Sleep and circadian abnormalities in patients with cirrhosis: features of delayed
      sleep phase syndrome?
AB  - Sleep disturbances are common in patients with cirrhosis but their origins are
      unknown. The aim of this study was to investigate possible involvement of the
      circadian system. Sleep was monitored for two weeks, in the home environment,
      using sleep diaries and actigraphy, in 35 patients with cirrhosis (21 men; mean
      age [+/- 1SD] 58 +/- 10 yr) and 12 matched healthy controls (eight men; mean age
      56 +/- 15 yr); urinary 6-sulphatoxymelatonin (aMT6s), the major metabolite of
      melatonin, was measured over 56 h, to assess circadian rhythmicity. The patients
      woke up and got up significantly later than the healthy volunteers and their
      sleep was significantly more fragmented. Mean 24-hour urinary aMT6s outputs were
      comparable in the patients and controls (15.5 +/- 13.1 vs. 20.3 +/- 13.8
      microg/24 h) but were significantly lower in the decompensated patients (9.8 +/-
      11.3 vs. 17.0 +/- 13.3 microg/24 h; p = 0.03). Significant 24-hour urinary aMT6s
      rhythms were observed in 26 (79%) of the 33 patients with complete urine
      collections; 20 patients had a normally timed (midnight-06:00) urinary aMT6s
      peak, while it was delayed (> or = 06:00) in the remainder. Significant
      correlations were observed between abnormalities in the urinary aMT6s profile
      (delays and/or lack of a 24-hour rhythm) and indices of sleep timing; parallel
      delays were observed in sleep habits and urinary aMT6s peaks. The association
      between delayed circadian rhythms and delayed sleep habits observed in
      approximately one-third of the patients with cirrhosis is reminiscent of 'delayed
      sleep phase syndrome'; this condition is managed by attempting to resynchronise
      the circadian clock by exposure to bright light shortly after morning awakening.

PMID- 19756997
TI  - Suppressive effect on MDC and IP-10 expression in monocytes by endocrine
      disruptor chemicals.
AB  - The expression of chemokines is critical in leukocyte recruitment and
      inflammation, but the regulatory mechanisms involved remain incompletely defined.
      While endocrine disrupter chemicals (EDCs) are known to be ubiquitous in the
      environment and often associated with altered inflammatory response, their
      potential impact on chemokine expression in monocytes is at present unknown. To
      this end, the effects of EDCs on the expression of Th1- and Th2-related
      chemokines in a human monocytic cell line, THP-1, were investigated. THP-1 cells
      were pre-treated with varying concentrations of EDCs (nonylphenol and 4
      octylphenol) with or without the addition of an estrogen receptor (ER)
      antagonist, ICI 182,780 and then stimulated by lipopolysaccharide (LPS). The
      levels of chemokines, CXCL10/ IFN-alpha-inducible protein 10 (IP-10, a Th1
      chemokine) and monocyte-derived chemokine (MDC)/CCL22, a Th2 chemokine) were
      measured by ELISA. EDC-mediated signaling events and histone modifications were
      examined by the use of Western blotting and chromatin immunoprecipitation (ChIP)
      assay. Nonylphenol and 4-octylphenol were able to suppress LPS-induced MDC and IP
      10 expression. This suppressive effect was not reversed by the addition of ICI
      182,780. Nonylphenol and 4-octylphenol reduced LPS-induced activation of MAPK
      signaling pathway, MKK1/2 and ERK, concomitant with decreased levels of LPS
      induced acetylated histone 4 (H4) at the IP-10 and MDC gene loci. Nonylphenol and
      4-octylphenol suppressed LPS-induced MDC expression in monocytes via, at least in
      part, the MKK1/2-ERK MAPK pathway and histone H4 acetylation, but not the
      estrogen receptor.

PMID- 19756998
TI  - Release of the soluble urokinase-type plasminogen activator receptor (suPAR) by
      activated neutrophils in rheumatoid arthritis.
AB  - Soluble form of the urokinase-type plasminogen activator receptor (suPAR) is
      markedly increased in biological fluids during different inflammatory conditions.
      It has previously been observed that the highest suPAR concentrations in
      inflammatory exudates tend to be associated with the presence of high number of
      neutrophils. Guided by this observation and our recent finding that activated
      neutrophils release suPAR we investigated whether neutrophils can be a source of
      suPAR during the inflammatory response in vivo. To address this question we
      conducted the comparative analysis of neutrophils isolated from the paired
      samples of synovial fluid (SF) and peripheral blood (PB) of rheumatoid arthritis
      patients. Freshly isolated SF neutrophils released significantly (p < 0.01)
      higher amounts of suPAR compared with PB neutrophils. We demonstrated that
      neutrophils from both sources release predominantly the truncated D2D3 form of
      suPAR. Migration of formyl peptide receptor-like 1 (FPRL1)-transfected human
      embryonic kidney (HEK) 293 cells toward the supernatants harvested from in vitro
      cultured SF neutrophils was significantly diminished when D2D3 form of suPAR was
      immunodepleted from the supernatants. Taken together, these data demonstrate that
      neutrophils, first, contribute to or are responsible for the generation of the
      increased suPAR levels during the inflammatory response and, second, release the
      chemotactically active form of suPAR that might be involved in the recruitment of
      formyl peptide receptors-expressing leukocytes into the inflamed tissues.

PMID- 19756999
TI  - Anti-inflammatory and immunomodulatory effects of Baccharis trimera aqueous
      extract on induced pleurisy in rats and lymphoproliferation in vitro.
AB  - Baccharis trimera is a widespread South American plant known as "carqueja".
      Medicinal teas prepared from the aerial parts of this plant are used in folk
      medicine in cases of liver diseases and inflammatory processes. We evaluated the
      effects of aqueous extract of B. trimera in the experimental inflammatory model
      of carrageenan-induced pleurisy in rat. The injection of carrageenan into the
      pleural cavity induces an influx of cells and fluid accumulation with a large
      number of polymorphonuclear leukocytes and increase of protein levels. The
      inflammation parameters were attenuated when B. trimera (400 and 800 mg/kg, i.p.)
      was administrated 30 min before the carrageenan. The immunomodulatory effects
      were evaluated in vitro on human peripheral blood mononuclear cells. The extract
      in concentration of 25, 50 and 100 mg/mL presented inhibited the T-lymphocytes
      proliferation stimulated by phytohemagglutinin, but these extract concentrations
      also presented cytotoxic effect. These results showed that the aqueous extract of
      B. trimera has anti-inflammatory effect.

PMID- 19757001
TI  - Echo Doppler guidance for atrial fibrillation ablation: recognition of primary
      electropathy.
AB  - Atrial fibrillation (AF) is a multivariable disease. Young patients with
      paroxysmal AF without structural cardiac abnormality ("lone AF") likely have a
      primary electropathy with excellent results from radiofrequency ablation.
      However, with persistent AF with cardiac abnormalities, including left atrial
      enlargement and systolic ventricular dysfunction (ejection fraction percent), the
      electropathy is considered secondary and ablation results poor. We describe a
      case with persistent AF, depressed systolic function, and marked left atrial
      enlargement but without echo Doppler evidence of diastolic dysfunction. At
      electrophysiology study, findings were consistent with a primary electropathy,
      and the patient did well following ablation.

PMID- 19757002
TI  - Esophagus imaging for catheter ablation of atrial fibrillation: comparison of two
      methods with showing of esophageal movement.
AB  - AIMS: This study aims to evaluate whether visualization and integration of the
      computed tomography (CT) scan of the left atrium (LA) and the esophagus into the
      three-dimensional (3D) electroanatomical map the day before ablation is accurate
      compared with integration of an esophagus tag into the electroanatomic LA map
      visualizing the anatomic relationship during the radiofrequency ablation or
      whether esophagus movement prohibits esophagus visualization the day before
      ablation. METHODS AND RESULTS: Eighteen patients with highly symptomatic atrial
      fibrillation underwent cardiac CT imaging the day before pulmonary vein ablation.
      Before CT imaging, a gastric tube was introduced into the esophagus allowing its
      CT 3D reconstruction. During radiofrequency ablation, mapping of the esophagus
      was performed and integrated into the LA 3D map. By comparing the position of the
      gastric tube during CT on day 1 with real-time anatomical mapping using a 3D
      navigation catheter on day 2, an average distance of more than 10 mm was found in
      six of 18 patients (33%). In six of 18 (33%), the maximal distance between day 1
      and day 2 was even more than 15 mm. CONCLUSION: Reliance on CT images, even if
      acquired within 24 h before ablation, does not ensure adequate intraprocedural
      localization of the esophagus or enhance recognition of esophageal motility.

PMID- 19757003
TI  - Simultaneous epicardial and endocardial substrate mapping and radiofrequency
      catheter ablation as first-line treatment for ventricular tachycardia and
      frequent ICD shocks in chronic chagasic cardiomyopathy.
AB  - BACKGROUND AND AIMS: Slow conduction scarred areas are related with ventricular
      tachycardia (VT) arrhythmogenesis in nonischemic cardiomyopathy. The purpose of
      this study was to characterize the substrate in both epicardial and endocardial
      surfaces of the left ventricle and to evaluate the effectiveness of substrate
      mapping and ablation for VT in Chagas cardiomyopathy. METHODS AND RESULTS:
      Seventeen patients were evaluated prospectively using a simultaneous epicardial
      and endocardial electroanatomical substrate mapping and ablation. With a mean of
      201 +/- 94 epicardial and 169 +/- 77 endocardial points, the epicardial voltage
      areas < or =0.5 mV were 56.8 +/- 40.6 (range 4.4 to 154.8 cm(2)) as compared to
      22.5 +/- 15.8 cm(2) (range 5.4 to 61.0 cm(2); p = 0.004) in the endocardium.
      Analyzing the epicardial surface, there was a strong correlation between the
      bipolar voltage electrograms and the electrogram duration at the epicardium
      during sinus rhythm (r = 0.897, p < 0.0001). Acute success was obtained in 83.3%
      of patients with no serious complications. At the end of follow-up from 14
      patients with acute success, 11 (78.6%) had been event-free based on implantable
      cardioverter defibrillator (ICD) interrogation logs. CONCLUSION: Chronic Chagas
      cardiomyopathy patients have larger epicardial as compared to endocardial
      substrate areas. Combined epicardial endocardial substrate mapping and ablation
      during sinus rhythm proves effective in preventing VT recurrences and appropriate
      ICD therapies.

PMID- 19757004
TI  - How can we improve the management of vascular risk in type 2 diabetes: insights
      from FIELD.
AB  - PURPOSE: Intensive multifactorial risk factor intervention, targeting blood
      glucose, blood pressure and low-density lipoprotein cholesterol, is central to
      therapeutic management of type 2 diabetes. This strategy reduces, but does not
      eliminate the risk for cardiovascular complications, and microvascular
      complications such as diabetic retinopathy and nephropathy still continue to
      develop or progress. Fibrates have been shown to be effective in managing mixed
      dyslipidemia characterized by elevated triglycerides and low high-density
      lipoprotein cholesterol (HDL-C), typically associated with type 2 diabetes.
      METHODS: Data were reviewed from the largest fibrate study to date, the
      Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study which
      evaluated the effect of fenofibrate treatment in 9,795 patients with type 2
      diabetes (about 80% without prior cardiovascular disease or microvascular
      complications). RESULTS: Although FIELD did not show a significant benefit with
      fenofibrate for major coronary events (the primary outcome), there was
      significant reduction in total cardiovascular events (relative risk reduction
      [RRR] 11%, p = 0.035 vs. placebo). The clinical benefits of fenofibrate treatment
      were greater in patients with marked mixed dyslipidemia (elevated triglycerides
      >or=200 mg/dL and low plasma levels of HDL-C), features of the metabolic syndrome
      commonly observed in patients with type 2 diabetes, with a RRR of 27%, p = 0.005.
      These data are consistent with evidence from other fibrate trials showing
      increased treatment benefits in patients with metabolic syndrome or type 2
      diabetes and mixed dyslipidemia. The FIELD study also provided promising data for
      microvascular benefits with fenofibrate, specifically on the need for laser
      treatment for diabetic retinopathy, progression of albuminuria, and prevention of
      diabetes-related lower-limb amputation. CONCLUSIONS: Adding fenofibrate to
      primary statin therapy might be a useful strategy to address residual
      macrovascular and microvascular risk in type 2 diabetes.

PMID- 19757005
TI  - Older adults in prime-time television dramas in Taiwan: prevalence, portrayal,
      and communication interaction.
AB  - A content and thematic analysis of 109 episodes (94.9 h) of prime-time dramas
      examined the portrayals of aging and the nature of intergenerational interaction
      involving older adults on Taiwanese television. The content analysis revealed
      that older characters, regardless of sex, appeared less frequently and in less
      prominent roles than other adult characters, but not in comparison to adolescents
      and children. The older characters who did appear, however, were predominantly
      portrayed as cognitively sound and physically healthy. The thematic analysis
      provided a different picture, showing that older characters talked about age
      explicitly, strategically linking it to death and despondence, to influence
      younger characters. Communication behavior themes identified included supporting,
      superiority, and controlling for older characters, and reverence/respect for
      younger characters. Findings are compared to those from similar studies of U.S.
      media and discussed from a Cultivation Theory perspective in terms of their
      reinforcement of Chinese age stereotypes and the traditional values of filial
      piety and age hierarchy in the context of globalization and culture change.

PMID- 19757006
TI  - Correlation-distortion based identification of Linear-Nonlinear-Poisson models.
AB  - Linear-Nonlinear-Poisson (LNP) models are a popular and powerful tool for
      describing encoding (stimulus-response) transformations by single sensory as well
      as motor neurons. Recently, there has been rising interest in the second- and
      higher-order correlation structure of neural spike trains, and how it may be
      related to specific encoding relationships. The distortion of signal correlations
      as they are transformed through particular LNP models is predictable and in some
      cases analytically tractable and invertible. Here, we propose that LNP encoding
      models can potentially be identified strictly from the correlation
      transformations they induce, and develop a computational method for identifying
      minimum-phase single-neuron temporal kernels under white and colored random
      Gaussian excitation. Unlike reverse-correlation or maximum-likelihood,
      correlation-distortion based identification does not require the simultaneous
      observation of stimulus-response pairs-only their respective second order
      statistics. Although in principle filter kernels are not necessarily minimum
      phase, and only their spectral amplitude can be uniquely determined from output
      correlations, we show that in practice this method provides excellent estimates
      of kernels from a range of parametric models of neural systems. We conclude by
      discussing how this approach could potentially enable neural models to be
      estimated from a much wider variety of experimental conditions and systems, and
      its limitations.

PMID- 19757007
TI  - Identification of new variants of SCMV causing sugarcane mosaic in India and
      assessing their genetic diversity in relation to SCMV type strains.
AB  - Sugarcane mosaic virus (SCMV) is one of the two causative viruses of mosaic in
      sugarcane, a sugar crop widely grown under tropical and subtropical conditions
      worldwide. Although molecular characterization of SCMV strains was reported from
      many countries, strains occurring in India, a major sugarcane producer have not
      been reported so far. Twenty-six sugarcane samples represented by seven major
      sugarcane growing states in India and USA were subjected to reverse-transcription
      polymerase chain reaction (RT-PCR) using a pair of newly designed coat protein
      specific primers. Among them 17 were found positive to the SCMV infection. The
      lengths of the sequences derived in this study using the new set of primers
      varied between 812 and 866 nt. The amino acid sequence comparison of 30 Indian
      SCMV isolates showed wide range of sequence similarities in core region (88.80
      100%) and hyper variable region (51.3-100%). In the N-terminal region of the five
      Indian isolates, a deletion of 12 aa residues between aa 11 and 30 was observed,
      whereas the deletion was between aa 45 and 50 in SCMV-B and -D and between aa 61
      and 70 in SCMV-A. The phylogenetic analyses performed with 46 SCMV CP sequences
      for both hyper variable region and core region separated the isolates mostly
      according to their geographical origin. The 30 Indian SCMV isolates were included
      exclusively in four groups besides SCMV-IND, which was grouped with SCMV-SC, a
      type of strain from Australia. Nearly 97.0% of the Indian isolates have no signs
      for close relationships with previously characterized SCMV type strains (SCMV-A, 
      B, -D, -E, and -SC) reported from other countries. Our studies revealed that the
      sugarcane mosaic in India are caused by at least nine new SCMV variants (IND-CC1,
      -CC2, -CC3, -CC4, -CO1, -CO2, -CP, -CS, and -J) and a type strain SCMV-SC
      represented by SCMV-IND. This is the first report on the variability and
      occurrence of new SCMV population in India.

PMID- 19757008
TI  - Molecular characterization and phylogenetic relationships of Desmodium leaf
      distortion virus (DeLDV): a new begomovirus infecting Desmodium glabrum in
      Yucatan, Mexico.
AB  - The complete DNA-A component sequence of Desmodium leaf distortion virus (DeLDV,
      Begomovirus) isolated in Yucatan was determined to be 2569 nucleotides (nt) in
      length, and it was most closely related to Cotton leaf crumple virus-California
      (CLCrV-[Cal]), at 76%. The complete DNA-B component sequence was 2514 nt in
      length, and shared its highest nucleotide identity (60%) with Potato yellow
      mosaic Trinidad virus (PYMTV). Phylogenetic analyses group the DeLDV DNA-A
      component in the SLCV clade, whereas, the DeLDV DNA-B was grouped with the
      Abutilon mosaic virus clade, which also contains PYMV, suggesting that the DeLDV
      components have distinct evolutionary histories, possibly as the result of
      recombination and reassortment.

PMID- 19757009
TI  - Cognitive representations of sexual self differ as a function of gender and
      sexual debut.
AB  - This research evaluated the association between gender and sexual debut (initial
      sexual intercourse) and indirect measures of sexuality. A sample of 440 U.S.
      college students (pre-sexual debut: 144 women, 153 men; post-sexual debut: 49
      women, 94 men) completed the Sexual Self-Schema Scale (SSSS), which assessed
      cognitive representations about sexual aspects of oneself, and three Implicit
      Association Tests (IAT), which measured the strength of the associations between
      the concepts of self + sex, women + sex, and men + sex. Results replicated
      previous findings that (1) men more strongly associated self + sex and women +
      sex than did women, and (2) men and women had similarly strong associations of
      men + sex. Post-sexual debut women's self + sexual and women + sexual
      associations were stronger than pre-sexual debut women's. Men's associations did
      not differ significantly as a function of sexual debut. Post-sexual debut women's
      SSSS scores were more direct, more romantic, and less conservative than pre
      sexual debut women's. Post-sexual debut men's SSSS scores were more aggressive
      and more open-minded than pre-sexual debut men's. Sexual debut appeared to be
      associated with sexualized and sexually liberal cognitive representations in
      women and, to a lesser extent, sexually liberal and aggressive cognitive
      representations in men. Findings were consistent with theories of cognitive
      consistency and provide preliminary evidence that sexual debut status was
      associated with differing cognitive representations.

PMID- 19757010
TI  - The DSM diagnostic criteria for transvestic fetishism.
AB  - This paper contains the author's report on transvestism, submitted on July 31,
      2008, to the work group charged with revising the diagnoses concerning sexual and
      gender identity disorders for the fifth edition of the American Psychiatric
      Association's Diagnostic and Statistical Manual of Mental Disorders (DSM). In the
      first part of this report, the author reviews differences among previous editions
      of the DSM as a convenient way to illustrate problems with the nomenclature and
      uncertainties in the descriptive pathology of transvestism. He concludes this
      part by proposing a revised set of diagnostic criteria, including a new set of
      specifiers. In the second part, he presents a secondary analysis of a pre
      existing dataset in order to investigate the utility of the proposed specifiers.

PMID- 19757011
TI  - Sexual behaviors among club drug users: prevalence and reliability.
AB  - HIV prevention efforts require a focus on reducing high risk sexual behavior.
      Because these are self-reported, assessments that reduce memory bias and improve
      elicitation of data are needed. As part of a multi-site psychometric study of
      club drug use, abuse, and dependence, data were collected with a test-retest
      design that measured the reliability of the Washington University Risk Behavior
      Assessment for Club Drugs (WU-RBA-CD). Reliability was assessed separately by sex
      via kappa coefficients and intraclass correlation coefficients (ICC); z tests
      compared coefficients by sex. A total of 603 participants were interviewed by
      independent assessors with 5 days in between interviews. Reliability for all 51
      items of the sexual activity section of the WU-RBA-CD ranged from .23 to 1.00;
      71% (n = 36) of items resulted in moderate to high reliability (.55-1.00). Number
      of lifetime sex partners was consistently reported for same-sex partners for both
      men and women and opposite-sex partners. Items with high reliability included
      reporting ever being under the influence of ecstasy (.87) or GHB (.87) while
      having sex. Items with lower reliability included those that queried the
      determinants of condom use (.45-.82) and about behaviors and attitudes
      experienced while using drugs (.23-.87). Very few sex differences were revealed
      in the reliability of reported sexual activities. Overall, the WU-RBA-CD
      performed with fairly high reliability rates. Assessing situations of when, how,
      and why individuals use condoms may offer the clearest evaluation of determinants
      of sexual behaviors, yet those items are not as reliable.

PMID- 19757012
TI  - The DSM diagnostic criteria for pedophilia.
AB  - This paper contains the author's report on pedophilia, submitted on June 2, 2008,
      to the work group charged with revising the diagnoses concerning sexual and
      gender identity disorders for the fifth edition of the American Psychiatric
      Association's Diagnostic and Statistical Manual of Mental Disorders (DSM). The
      author reviews the previously published criticisms and empirical research
      concerning the diagnostic criteria for pedophilia and presents criticism and
      relevant research of his own. The review shows that the DSM diagnostic criteria
      for pedophilia have repeatedly been criticized as unsatisfactory on logical or
      conceptual grounds, and that published empirical studies on the reliability and
      validity of these criteria have produced ambiguous results. It therefore seems
      that the current (i.e., DSM-IV-TR) diagnostic criteria need to be examined with
      an openness to major changes in the DSM-V.

PMID- 19757013
TI  - Influences of mastery, spousal support, and adaptive coping on sexual drive and
      satisfaction among chinese gynecologic cancer survivors.
AB  - This study investigated sexual drive and satisfaction of Chinese gynecologic
      cancer survivors. It also examined the extent to which personal mastery, adaptive
      coping, and perceived spousal support would exert direct and/or indirect
      influences on sexual outcomes. The cancer survivor group included 134 Chinese
      women who had received treatment for gynecologic cancer, while the healthy
      control group included 105 Chinese women who did not have a known history or
      current diagnosis of cancer. Compared to healthy women, cancer survivors reported
      lower levels of sexual drive and sexual satisfaction. Among sexually active
      participants, cancer survivors relative to healthy women engaged in less
      masturbation, less kissing and caressing, and less sexual fantasy in the past
      month. Hierarchical multiple regression analyses showed that mastery and spousal
      support, but not adaptive coping, had a direct influence on sexual outcomes in
      cancer survivors. Contrary to moderation hypotheses, the three psychological
      factors did not interact with each other to influence sexual drive and
      satisfaction. Mediation analyses showed that spousal support fully mediated the
      influence of mastery on sexual satisfaction. Routine assessment of sexual
      functioning prior to and following treatment of gynecologic cancer is suggested.
      Sexual rehabilitation should also aim to enhance personal mastery and spousal
      support.

PMID- 19757014
TI  - Pathways between socioeconomic status and modifiable risk factors among African
      American smokers.
AB  - Although socioeconomic status is a major contributing factor to health
      disparities, the mechanisms through which socioeconomic status influences health
      remain unclear. The purpose of the present study was to evaluate an a priori
      conceptual model of the pathways between socioeconomic status and modifiable
      health risk factors in a sample of 399 African Americans seeking smoking
      cessation treatment. A latent variable modeling approach was utilized to
      characterize the interrelationships among socioeconomic status, neighborhood
      disadvantage, social support, negative affect/perceived stress, and three
      specific modifiable risk factors (i.e., overweight/obesity, insufficient physical
      activity, at-risk drinking). Findings indicated that neighborhood disadvantage,
      social support, and negative affect/perceived stress function as pathways linking
      socioeconomic status and modifiable risk factors among African American smokers,
      and negative affect/perceived stress appears to play a key mediating role.
      Policy, community, and individual-level interventions may attenuate the impact of
      socioeconomic status on health by targeting intermediate psychosocial,
      environmental, and behavioral pathways.

PMID- 19757015
TI  - Negative emotions and quality of life six months after cardiac surgery: the
      dominant role of depression not anxiety symptoms.
AB  - The specific syndromal aspects of depression and anxiety have not been explored
      in relation to changes in health related quality of life (HRQOL) after cardiac
      surgery. The purpose of this study was to examine the impact of general stress,
      depression and anxiety on HRQOL after coronary artery bypass graft (CABG)
      surgery. Utilizing a tripartite conceptual model of depression and anxiety, it
      was hypothesized that general stress symptoms, rather than unique depressive or
      anxiogenic symptoms, would be associated with lower HRQOL 6 months after CABG
      surgery. Elective CABG patients (n=226) completed baseline and postoperative self
      report measures of negative emotions and HRQOL, and 193 patients completed these
      measures at 6-month follow-up. Multiple linear regression analyses and logit link
      analyses were performed to test the hypothesis. Elevated depression symptoms
      before and after surgery showed an association with lower and worse HRQOL for
      vitality and social role functioning and physical and general health. This study
      adds to previous research by outlining discrete associations between specific
      HRQOL domains, and is perhaps the first to test a theoretical model of depression
      and anxiety in relation to cardiac CABG patients' perceptions of HRQOL. These
      findings encourage further research on negative emotions and HRQOL in cardiac
      surgery patients and the practical implications of these findings are discussed.

PMID- 19757016
TI  - Introgression of Brown Norway chromosome 1 onto the fawn hooded hypertensive
      background rescues long-term fear memory deficits.
AB  - The isolation of genes influencing long-term memory is critical for an
      understanding of learning at the molecular level. Recently, chromosomal
      substitution rat strains, known as consomics, have been developed. Here we report
      the results of the first study on aversive learning and memory with these
      consomic rats. We compared the Fawn Hooded Hypertensive (FHH) and Brown Norway
      (BN) parent strains with a Brown Norway chromosome 1 substitution on the FHH
      background (FHH-1(BN)). Results indicated that while all strains had normal short
      term memory, the FHH animals were impaired relative to BN in tests of long-term
      memory for a discrete auditory cue. This deficit was rescued by the introgression
      of the BN1 chromosome onto the FHH background. Furthermore, the FHH-1(BN)
      consomic showed an enhancement in long-term contextual fear memory relative to
      the FHH strain. These changes were not due to differences in pain sensitivity as
      both strains performed equally on two different pain tests. These results provide
      preliminary support that consomic rat strains can be a useful tool in identifying
      genes related to long-term fear memory formation.

PMID- 19757017
TI  - Acceptability of UC781 gel as a rectal microbicide among HIV-uninfected women and
      men.
AB  - We studied the overall acceptability of UC781 gel formulation when applied
      rectally. Ten women and twenty-six men, all HIV-uninfected, were enrolled in a
      Phase 1, randomized, blinded, placebo-controlled safety and acceptability study
      of the vaginal microbicide gel UC781 applied rectally. Participants were
      randomized to three groups: 0.1% UC781 gel, 0.25% UC781 gel, or a placebo gel.
      Acceptability was assessed using structured questionnaires and qualitative in
      depth interviews. After using UC781 gel rectally for seven consecutive days,
      participants' reports suggest that a UC781 gel formulation is highly acceptable
      and comparable to a placebo gel. The gels received favorable ratings overall and
      on attributes such as color, smell and consistency. All of the participants
      reported high intentions to use a gel like the one they used in this study.
      Acceptability research is essential in early phases of microbicide development to
      identify potential problems, understand user preferences, and introduce changes
      if needed.

PMID- 19757018
TI  - Acceptability and use of the diaphragm and Replens lubricant gel for HIV
      prevention in Southern Africa.
AB  - The acceptability and use of the diaphragm and lubricant gel were assessed as
      part of a large randomized controlled trial to determine the effectiveness of the
      methods in women's HIV acquisition. 2,452 intervention-arm women were enrolled at
      five Southern African clinics and followed quarterly for 12-24 months.
      Acceptability and use data were collected by face-to-face interviews at Month 3
      and Exit. Participants were "very comfortable" with the physical mechanics of
      diaphragm use throughout the trial, and approval of the gel consistency, quantity
      and the applicator was high. At Exit, consistent disclosure of use (AOR 1.97, 95%
      CI: 1.10-3.55); an overall high diaphragm rating (AOR 1.84, 95% CI: 1.45-2.34)
      and perception of partner approval (AOR 1.75, 95% CI: 1.35-2.26) were the most
      significant acceptability factors independently associated with consistent use.
      Despite being female-initiated, disclosure of use to male partners and his
      perceived approval of the products were factors significantly associated with
      their consistent use.

PMID- 19757019
TI  - Reducing HIV risks among active injection drug and crack users: the safety counts
      program.
AB  - The efficacy of Safety Counts, a CDC-diffused intervention, was reanalyzed. In a
      quasi experimental, cross-over design, injection drug users (IDU) and crack users
      in two neighborhoods were assigned by neighborhood to receive individual
      Voluntary HIV Counseling and Testing or Safety Counts and 78% were reassessed at
      5-9 months. Drug users in the Safety Counts program reported significantly
      greater reductions in risky sex, crack and hard drug use, and risky drug
      injection. The more sessions of Safety Counts attended, the greater were the
      reductions in risky acts. Different analytic decisions result in very different
      findings for the same intervention. Safety Counts is an effective intervention
      for IDU and crack users. Analytic decision of intervention outcomes is highly
      related to evaluations of an intervention's efficacy.

PMID- 19757020
TI  - Development of a patient-report measure of psychotherapy for depression.
AB  - Despite clear indications of need to improve depression treatment, practical
      tools that efficiently measure psychotherapy are not available. We developed a
      patient-report measure of psychotherapy for depression that assesses Cognitive
      Behavioral (CBT), Interpersonal (IPT), and Psychodynamic therapies. 420 patients
      with depression from a large managed behavioral health care organization
      completed the measure. The three subscales measuring CBT, IPT, and Psychodynamic
      Therapy showed good internal consistency, appropriate item-total correlations,
      and were supported by a 3-factor structure. Our results suggest that a patient
      questionnaire is a promising approach for assessing psychotherapy in quality
      improvement interventions.

PMID- 19757021
TI  - Methodological challenges of characterizing usual care psychotherapeutic
      practice.
AB  - There is minimal existing research providing detailed, reliable data
      characterizing usual community-based psychotherapy practice, and, thus, limited
      established methods for such research. This article identifies methodological
      challenges of usual care descriptive research, including, (a) general design
      considerations, (b) measurement, (c) data analytic, and (d) ethical challenges.
      Case examples drawn from studies reported in this special issue are used to
      illustrate the implications, strengths, and weaknesses of different
      methodological decisions. Central themes include achieving an acceptable balance
      of scientific rigor, feasibility, and generalizable practice relevance, as well
      as working collaboratively with practice partners to select and implement study
      methods.

PMID- 19757022
TI  - The synaptic remodeling between regenerated perforant pathway and granule cells
      in slice culture.
AB  - In order to understand the synaptic remodeling in the course of axonal
      regeneration, the synaptic remodeling of the perforant path in hippocampus was
      investigated in the present study with entorhino-hippocampal coculture, DiI
      DiOlistic assay and transmission electron microscopy. The results showed that the
      regeneration of the perforant pathway occurred in entorhino-hippocampal slice
      coculture, and putative synaptic contacts formed between the regenerated fibers
      and dendritic spines of granule cells. Ultrastructural analysis confirmed the
      formation of new synaptic contacts. In conclusion, the synaptic formation
      implicated in the neuroregeneration could integrate into the network in CNS.

PMID- 19757023
TI  - Therapeutic DNA vaccination as a repair strategy following spinal cord injury.
AB  - Myelin-derived proteins, such as tenascin-R (TN-R), myelin associate glycoprotein
      (MAG), oligodendrocyte-myelin glycoprotein (OMgp), and Nogo-A, inhibit the
      central nervous system regeneration. In this study, the DNA vaccine encoding for
      oligodendrocyte and myelin-related antigens was employed to attenuate the axonal
      growth inhibitory properties of myelin in the setting of spinal cord injury.
      Using a rat spinal cord dorsal hemisection model, the vaccine directed against
      the inhibitory epitopes of Nogo-A, MAG, OMgp, and TN-R was administered
      intramuscularly once a week following spinal cord injury, supplemented with local
      application of specific anti-sera against the four antigens. Anterograde labeling
      of dorsal column fibers showed active axonal regeneration through the lesion site
      at the eighth week following the treatment in experimental group but not in
      control groups. Light microscopic and ultrastructural analysis revealed that
      vaccination with these myelin-related antigens did not lead to demyelinating
      disease. OMgp and TN-R levels were down-regulated at the lesion site together
      with a parallel increase in growth-associated protein 43 levels in the treatment
      groups. This study reveals the effective approach of a DNA vaccine strategy by
      attaining the special antibody to direct neutralization of the myelin inhibitors
      during spinal cord injury.

PMID- 19757024
TI  - Study on DBH genetic polymorphisms and plasma activity in attention deficit
      hyperactivity disorder patients from Eastern India.
AB  - Dysfunctions in the norepinephric pathway have been speculated in the etiology of
      attention deficit hyperactivity disorder (ADHD), a common problem for children.
      Synthesis of norepinephrine from dopamine is catalyzed by the enzyme dopamine
      beta-hydroxylase and numerous polymorphisms in the DBH gene have been found to
      exert their direct influence on the enzyme activity independently. In the present
      study association of ADHD with four genetic polymorphisms, DBH-STR, rs1611115,
      rs1108580, and rs2519152, was examined in subjects belonging to eastern India.
      ADHD subjects (n = 111) were recruited following DSM-IV criteria. Peripheral
      blood samples were collected from nuclear families with ADHD probands. A group of
      ethnically matched healthy volunteers (n = 130) was also recruited. Genomic DNA
      was analyzed by PCR amplification followed by restriction digestion and
      genotyping. Data obtained were subjected to both family-based as well as
      population-based statistical analyses. Plasma DbetaH activity was measured using
      a photometric assay and its correlation with the genetic polymorphisms was
      analyzed using analysis of variance. Case-control analysis revealed no
      significant differences in allelic frequencies; however, significant paternal
      over-transmission (P = 0.02) of the rs2519152 'G' allele to ADHD probands was
      noticed. A haplotype, composed of 12R-C-G-G, also showed biased transmission.
      Strong correlation was observed between enzyme activity and rs1611115, rs1108580,
      and rs2519152 (P = 1.51E-6, 0.04, and 0.003, respectively). The present study
      hints toward the fact that DBH gene polymorphisms have some role in the etiology
      of ADHD in eastern Indian population and their study could be useful for
      therapeutic intervention.

PMID- 19757025
TI  - Has the influence of managed care waned? Evidence from the market for physician
      services.
AB  - Managed care has been the dominant organization of health care coverage in the
      United States, and seeks to achieve cost control by constraining services. The
      restrictive practices of managed care organizations have been widely criticized
      and the role of managed care in constraining health care services may be
      declining. Physician behavior is also believed to be influenced by the practices
      of managed care organization. This study examines the evolving nature of managed
      care and its restrictive effects on the provision of physician services.
      Physicians can choose whether and to what extent they are involved in managed
      care, so it is an endogenous decision. We employ instrumental variables method to
      correct for this endogeneity. Using data from the Community Tracking Study
      physician surveys from 2000-2001 and 2004-2005, we find that managed care
      organizations have became relatively less restrictive over time in terms of
      limiting the provision of physician services, compared to non-managed care
      organizations. These results suggest that managed care and non-managed care are
      converging in their effects on the provision of physician services.

PMID- 19757026
TI  - Multimeric bivalent immunogens from recombinant tetanus toxin HC fragment,
      synthetic hexasaccharides, and a glycopeptide adjuvant.
AB  - Using recombinant tetanus toxin H(C) fragment (rTT-H(C)) as carrier, we prepared
      multimeric bivalent immunogens featuring the synthetic hexasaccharide fragment of
      O-PS of Vibrio cholerae O:1, serotype Ogawa, in combination with either the
      synthetic hexasaccharide fragment of O-PS of Vibrio cholerae O:1, serotype Inaba,
      or a synthetic disaccharide tetrapeptide peptidoglycan fragment as adjuvant. The
      conjugation reaction was effected by squaric acid chemistry and monitored in
      virtually real time by SELDI-TOF MS. In this way, we could prepare well-defined
      immunogens with predictable carbohydrate-carrier ratio, whose molecular mass and
      the amount of each saccharide attached could be independently determined. The
      ability to prepare such neoglycoconjugates opens unprecedented possibilities for
      preparation of conjugate vaccines for bacterial diseases from synthetic
      carbohydrates.

PMID- 19757027
TI  - Eryptosis in hereditary spherocytosis and thalassemia: role of glycoconjugates.
AB  - The present work is aimed to study the mechanism of faster erythrocyte clearance
      in hereditary spherocytosis (HS), a heterogeneous disorders characterized by
      alterations in the proteins of the red cell membrane skeleton along with
      different kinds of thalassemia. The maximum exposure of phosphatidylserine (PS)
      is found in HS compared to those in both alpha- and beta-thalassemia.
      Interestingly, in HS more PS exposed cells were found in younger erythrocytes
      compared to normal and the thalassemics where aged cells showed higher loss of PS
      asymmetry. Loss of sialic acid and GlcNAc bearing glycoconjugates, presumably the
      glycophorins, was also found upon aging. The loss of PS asymmetry together with
      the cell surface glycoproteins mediated by membrane vesiculation, seemed to play
      key role in early clearance of erythrocytes from circulation following a
      mechanism similar to HbEbeta-thalassemia.

PMID- 19757028
TI  - Infection-associated FUT2 (Fucosyltransferase 2) genetic variation and impact on
      functionality assessed by in vivo studies.
AB  - The secretor (Se)/nonsecretor (se) histo-blood group variation depends on the
      action of the FUT2 enzyme and has major implications for human susceptibility to
      infections. To characterize the functionality of FUT2 variants, we assessed the
      correlation between saliva phenotypes and sequence variation at the FUT2 gene in
      sixty seven individuals from northern Portugal. While most non-secretor
      haplotypes were found to carry the 428G > A nonsense mutation in association with
      a 739G > A missense substitution, we have also identified a recombinant haplotype
      carrying the 739*A allele together with the efficient 428*G variant in
      individuals with the Se phenotype. This finding suggested, in contrast to
      previous results, that the 739*A allele encodes an efficient Se allele. To test
      this hypothesis we evaluated the in vivo enzyme activity of full coding
      expression constructs in transient transfection of CHO-K1 cells using FACS
      (fluorescence-activated cell sorting) analysis and expression of type 2 and type
      3 chain H structures as read out. We detected FUT2 activity for the 739*A
      expression construct, demonstrating that the 739G > A substitution is indeed not
      inactivating. In accordance with the hypothesis that FUT2 is under long standing
      balancing selection, we estimated that the time depth of FUT2 global genetic
      variation is as old as 3 million years. Age estimates of specific variants
      suggest that the 428G > A mutation occurred at least 1.87 million years ago while
      the 739G > A substitution is about 816,000 years old. The 385A > T missense
      mutation underlying the non-secretor phenotype in East Asians appears to be more
      recent and is likely to have occurred about 256,000 years ago.

PMID- 19757029
TI  - Architecture of the left ventricle: insights for optimal surgical ventricular
      restoration.
AB  - The normal left ventricular shape has been defined as prolate ellipsoid. This
      shape is an adaptation to evolution. A knowledge of its unique macro and micro
      architecture forms the cornerstone in the understanding of its complex function.
      The left ventricle has a unique architecture with three different myofiber
      orientations, the longitudinal, circumferential and oblique fibers. The oblique
      orientation of fibers is essential for effective clockwise and anticlockwise
      torsional movements during systole and diastole, for optimal ventricular ejection
      and filling. The orientation and fiber angle decide the shape of the ventricle.
      An ellipsoid shape is vital for optimal function. Pathological disease states
      such as ischemic heart disease, valvular heart disease and cardiomyopathies cause
      a loss of obliquity of the myofibers. The myofibers become more horizontal
      resulting in ventricular dilatation and increased sphericity. The change from
      ellipsoid to globular shape with disease heralds the onset of left ventricular
      dysfunction and initiates the cascade of heart failure. Several strategies have
      been successful in reverting ventricular dilatation and sphericity to a more
      ellipsoid geometry. Pharmacological therapies like beta blockade and angiotensin
      converting enzyme inhibition have proven beneficial in early stages of heart
      failure with pathological remodeling. However, these agents in isolation are
      limited in reversing pathological remodeling in advanced heart failure. In some
      cases of advanced heart failure due to postinfarction left ventricular aneurysms,
      ventricular volume reduction with restoration surgeries have a role in restoring
      ventricular geometry with beneficial clinical outcomes. Surgical ventricular
      restoration has progressively evolved from the 1950s. Initially, aneurysmal
      resection and linear repair was done. This was gradually replaced by
      endoventricular patch plasty, which had better results. The resulting left
      ventricle was smaller in size but still continued to have a spherical
      configuration. Exclusion of the infarct area with a smaller longitudinal patch
      results in realignment of the non-diseased ventricular fibers with a resulting
      ellipsoid shape. This ellipsoid shape ensures clinical benefits. The geometry of
      the endoventricular patch thus holds the key to optimal ventricular shape in
      these patients. The technique to optimally restore a diseased ventricle to normal
      continues to evolve. This requires insights into the normal architecture and
      function, and the pathophysiologic effects of disease.

PMID- 19757030
TI  - Ecotoxicological assessment of industrial effluent using duckweed  (Lemna minor
      L.) as a test organism.
AB  - This study aimed at assessing the toxic effects of industrial effluents using
      duckweed (Lemna minor L.) plants as a test system. Growth inhibition test
      according to standardized protocol (ISO 20079) was performed. The suitability of
      the Comet assay (indicates DNA damage) and certain parameters such as peroxidase
      activity and lipid peroxidation level, as biomarkers for environmental monitoring
      was evaluated. The water samples were collected monthly over a 3-month period
      from the stream near the industrial estate of Savski Marof, Croatia. All samples
      caused inhibition of growth rates based on frond number and biomass as well as
      decrease of chlorophylls content. In contrast, peroxidase activity,
      malondialdehyde content and tail extent moment (measure of DNA strand breaks)
      markedly increased. Obtained data demonstrate the relevance of duckweed as
      sensitive indicators of water quality as well as the significance of selected
      biological parameters in the reliable assessment of phyto- and genotoxic
      potential of complex wastewaters.

PMID- 19757031
TI  - Risk assessment for side-effects of neonicotinoids against  bumblebees with and
      without impairing foraging behavior.
AB  - Bombus terrestris bumblebees are important pollinators of wild flowers, and in
      modern agriculture they are used to guarantee pollination of vegetables and
      fruits. In the field it is likely that worker bees are exposed to pesticides
      during foraging. To date, several tests exist to assess lethal and sublethal side
      effects of pesticides on bee survival, growth/development and reproduction.
      Within the context of ecotoxicology and insect physiology, we report the
      development of a new bioassay to assess the impact of sublethal concentrations on
      the bumblebee foraging behavior under laboratory conditions. In brief, the
      experimental setup of this behavior test consists of two artificial nests
      connected with a tube of about 20 cm and use of queenless micro-colonies of 5
      workers. In one nest the worker bees constructed brood, and in the other food
      (sugar and pollen) was provided. Before exposure, the worker bees were allowed a
      training to forage for untreated food; afterwards this was replaced by treated
      food. Using this setup we investigated the effects of sublethal concentrations of
      the neonicotinoid insecticide imidacloprid, known to negatively affect the
      foraging behavior of bees. For comparison within the family of neonicotinoid
      insecticides, we also tested different concentrations of two other
      neonicotinoids: thiamethoxam and thiacloprid, in the laboratory with the new
      bioassay. Finally to evaluate the new bioassay, we also tested sublethal
      concentrations of imidacloprid in the greenhouse with use of queenright colonies
      of B. terrestris, and here worker bees needed to forage/fly for food that was
      placed at a distance of 3 m from their hives. In general, the experiments showed
      that concentrations that may be considered safe for bumblebees can have a
      negative influence on their foraging behavior. Therefore it is recommended that
      behavior tests should be included in risk assessment tests for highly toxic
      pesticides because impairment of the foraging behavior can result in a decreased
      pollination, lower reproduction and finally in colony mortality due to a lack of
      food.

PMID- 19757032
TI  - The mysid Siriella armata as a model organism in marine  ecotoxicology:
      comparative acute toxicity sensitivity  with Daphnia magna.
AB  - Siriella armata (Crustacea, Mysidacea) is a component of the coastal zooplankton
      that lives in swarms in the shallow waters of the European neritic zone, from the
      North Sea to the Mediterranean. Juveniles of this species were examined as
      standard test organisms for use in marine acute toxicity tests. The effects of
      reference toxicants, three trace metals (Copper, Cadmium and Zinc), and one
      surfactant, sodium dodecyl sulfate (SDS) were studied on S. armata neonates (?24
      h) reared in the laboratory. Acute toxicity tests were carried out with filtered
      sea water on individual chambers (microplate wells for metals or glass vials for
      SDS) incubated in an isothermal room at 20 degrees C, with 16 h light: 8 h dark
      photoperiod for 96 h. Each neonate was fed daily with 10-15 nauplii of Artemia
      salina. Acute (96 h) LC50 values, in increasing order, were 46.9 lg/L for Cu,
      99.3 lg/L for Cd, 466.7 lg/L for Zn and 8.5 mg/L for SDS. The LC(10), NOEC and
      LOEC values were also calculated. Results were compared with Daphnia magna, a
      freshwater cladoceran widely used as a standard ecotoxicological test organism.
      Acute (48 h) LC(50) values were 56.2 lg/L for Cu, 571.5 lg/L for Cd, 1.3 mg/L for
      Zn and 27.3 mg/L for SDS. For all the reference toxicants studied, the marine
      mysid Siriella armata showed higher sensitivity than the freshwater model
      organism Daphnia magna, validating the use of Siriella mysids as model organisms
      in marine acute toxicity tests.

PMID- 19757033
TI  - In vitro cell-toxicity screening as an alternative animal model  for coral
      toxicology: effects of heat stress, sulfide, rotenone,  cyanide, and cuprous
      oxide on cell viability and mitochondrial  function.
AB  - The logistics involved in obtaining and maintaining large numbers of corals
      hampers research on the toxicological effects of environmental contaminants for
      this ecologically and economically important taxon. A method for creating and
      culturing single-cell suspensions of viable coral cells was developed. Cell
      segregation/separation was based on specific cell densities and resulting cell
      cultures were viable for at least 2 mos. Low-density cells lacking symbiotic
      zooxanthallae and rich in mitochondria were isolated and cultured for toxicity
      studies. Cells were exposed to differing degrees or concentrations of heat
      stress, rotenone, cyanide, sulfide, and cuprous oxide. Cells were assayed for
      mitochondrial membrane potential using the fluorescent probe, JC-9, and for
      overall viability using the MTT/formazan spectrophotometric viability assay.
      Significant differences were observed between controls and treatments and the
      efficacy of this method was validated; only 2 cm(2) of tissue was required for a
      seven-point concentration-exposure series.

PMID- 19757034
TI  - The extracellular matrix protein SC1/Hevin localizes to multivesicular bodies in
      Bergmann glial fibers in the adult rat cerebellum.
AB  - SC1 is an extracellular matrix molecule prominent in the mammalian brain. In the
      cerebellum, SC1 localizes to Bergmann glial cells and perisynaptic glial
      processes that envelop synapses in the molecular layer. In the present study,
      confocal microscopy revealed a punctate distribution of SC1 along Bergmann glial
      fibers that colocalized with the intermediate filament GFAP when fibers were
      viewed in cross-section. Immunoelectron microscopy showed that the punctate SC1
      pattern corresponded to the localization of SC1 in multivesicular bodies situated
      within Bergmann glial fibers. The pattern of SC1 localization was not disrupted
      following hyperthermia or pilocarpine-induced status epilepticus. The present
      study suggests that SC1 protein may reach its destination in perisynaptic glial
      processes and glial endfeet by transport along Bergmann glial fibers in
      multivesicular bodies and that this process is preserved following stress.

PMID- 19757035
TI  - Promotion of lipid and protein oxidative damage in rat brain by ethylmalonic
      acid.
AB  - High concentrations of ethylmalonic acid are found in tissues and biological
      fluids of patients affected by ethylmalonic encephalopathy, deficiency of short
      chain acyl-CoA dehydrogenase activity and other illnesses characterized by
      developmental delay and neuromuscular symptoms. The pathophysiological mechanisms
      responsible for the brain damage in these patients are virtually unknown.
      Therefore, in the present work we investigated the in vitro effect of EMA on
      oxidative stress parameters in rat cerebral cortex. EMA significantly increased
      chemiluminescence and thiobarbituric acid-reactive species levels
      (lipoperoxidation), as well as carbonyl content and oxidation of sulfhydryl
      groups (protein oxidative damage) and DCFH. EMA also significantly decreased the
      levels of reduced glutathione (non-enzymatic antioxidant defenses). In contrast,
      nitrate and nitrite levels were not affected by this short organic acid. It is
      therefore presumed that oxidative stress may represent a pathomechanism involved
      in the pathophysiology of the neurologic symptoms manifested by patients affected
      by disorders in which EMA accumulates.

PMID- 19757036
TI  - Cocaine induces alterations in mitochondrial membrane potential and dual cell
      cycle arrest in rat c6 astroglioma cells.
AB  - Investigations with astroglial cells carry more prominence in drug abuse studies.
      However, due to earlier perception that astroglial cells were only passive
      bystanders in neural signal transmission, not many investigations were conducted
      on the toxicity of various abused drugs, like cocaine. The present study was
      aimed to discern the effect of cocaine on rat astroglioma cells and analyzed
      qualitatively for morphological features as well as vacuolation by phase contrast
      microscope, quantitatively for cytotoxicity, mitochondrial membrane potential by
      rhodamine- 123 fluorometric assay, and cell cycle analysis by flow cytometry.
      Based on population cell doubling time studies, glial cells were grown in 10% FBS
      in RPMI 1640 medium and treated with cocaine for 24 or 48 h. Microscopic
      assessments clearly demonstrated massive vacuolation and significant disruption
      at general architecture of glial cell morphology with cocaine. Chronic cocaine
      treatment (24 or 48 h) caused significant loss of cell viability. The sublethal
      dose of cocaine was found to be 4.307 and 3.794 mM at 24 and 48 h, respectively.
      Cocaine reduced the mitochondrial membrane potential in a dose dependent manner
      with ED(50) of 4 mM after 24 h. Cell cycle analysis suggested dual inhibition at
      G0/G1 and G2/M phases after 24 and 48 h, respectively. In summary, our findings
      suggest that cocaine toxicity was due to loss of mitochondrial membrane
      potential, vacuolation, and dual inhibition of cell cycle phases. These results
      may shed light in understanding the onset of some early key events in cocaine
      induced toxicity in glial cells.

PMID- 19757037
TI  - Scopolamine induced amnesia is reversed by Bacopa monniera through participation
      of kinase-CREB pathway.
AB  - Scopolamine, an anticholinergic drug, is reported to produce amnesia by
      interference of long term potentiation and has been used for discerning the
      efficacy of various antiamnesic drugs. The intoxication with anticholinergics and
      benzodiazepines tend to produce neurodegeneration which cause memory deficits.
      Our earlier reports have shown the antiamnesic drug, B. monniera to be capable of
      alleviating diazepam induced memory deficits. We have now tested how scopolamine
      affects downstream signaling molecules of long term potentiation and if B.
      monniera can also modulate the scopolamine induced amnesia. We used Morris water
      maze scale to test the amnesic effect of scopolamine and its reversal by B.
      monniera. Rota-rod test was used to screen muscle coordination activity of mice
      before water maze investigations were carried out. The results showed that
      scopolamine downregulated protein kinase C and iNOS without affecting cAMP,
      protein kinase A, calmodulin, MAP kinase, nitrite, CREB and pCREB. B. monniera
      reversed the scopolamine induced amnesia by significantly improving calmodulin
      and by partially attenuating protein kinase C and pCREB. These observations
      suggest involvement of calmodulin in evoking antiamnesic effects of B. monniera.

PMID- 19757038
TI  - SSeCKS is a suppressor in Schwann cell differentiation and myelination.
AB  - Src-suppressed protein kinase C substrate (SSeCKS) plays an important role in the
      differentiation process. In regeneration of sciatic nerve injury, expression of
      SSeCKS decreases, mainly in Schwann cells. However, the function of SSeCKS in
      Schwann cells differentiation remains unclear. We observed that SSeCKS was
      decreased in differentiated Schwann cells. In long-term SSeCKS-reduced Schwann
      cells, cell morphology changed and myelin gene expression induced by cAMP was
      accelerated. Myelination was also enhanced in SSeCKS-suppressed Schwann cells co
      culture with dorsal root ganglion (DRG). In addition, we found suppression of
      SSeCKS expression promoted Akt serine 473 phosphorylation in cAMP-treated Schwann
      cells. In summary, our data indicated that SSeCKS was a negative regulator of
      myelinating glia differentiation.

PMID- 19757039
TI  - Measurement error correction for the cumulative average model in the survival
      analysis of nutritional data: application to Nurses' Health Study.
AB  - The use of the cumulative average model to investigate the association between
      disease incidence and repeated measurements of exposures in medical follow-up
      studies can be dated back to the 1960s (Kahn and Dawber, J Chron Dis 19:611-620,
      1966). This model takes advantage of all prior data and thus should provide a
      statistically more powerful test of disease-exposure associations. Measurement
      error in covariates is common for medical follow-up studies. Many methods have
      been proposed to correct for measurement error. To the best of our knowledge, no
      methods have been proposed yet to correct for measurement error in the cumulative
      average model. In this article, we propose a regression calibration approach to
      correct relative risk estimates for measurement error. The approach is
      illustrated with data from the Nurses' Health Study relating incident breast
      cancer between 1980 and 2002 to time-dependent measures of calorie-adjusted
      saturated fat intake, controlling for total caloric intake, alcohol intake, and
      baseline age.

PMID- 19757041
TI  - Disaster in context: the effects of 9/11 on youth distant from the attacks.
AB  - Although an increasing amount of community mental health research has
      investigated the deleterious effects of disasters and the targeting and efficacy
      of treatment in their aftermath, little research has sought to identify
      preexisting characteristics of the social environment that are predictive of post
      disaster distress. A national US telephone survey fielded before and after
      September 11, 2001, was used to investigate the psychological distress among
      American adolescents related to the attacks, and to identify environmental and
      other characteristics that predisposed youth to experience higher or lower levels
      of post-disaster distress. The study found that widespread characteristics of
      children's school environments-school disorder and physical threats-were at least
      as strongly associated with a proxy for psychological distress as exposure to the
      events of 9/11. Further, children exposed to physical threats at school appeared
      to be more vulnerable to the psychological effects of disasters than children in
      safer school environments.

PMID- 19757042
TI  - Proinflammatory Th2 cytokines induce production of thymic stromal lymphopoietin
      in human colonic epithelial cells.
AB  - PURPOSE: Thymic stromal lymphopoietin (TSLP) is released by intestinal epithelial
      cells (IECs), and TSLP-conditioned dendritic cells appear to be involved in
      immune homeostasis of intestine and immunoglobulin A (IgA) class-switching in the
      physiological condition. In contrast, TSLP activates dendritic cells to induce
      strong T-cell proliferation and is involved in inflammatory T helper (Th) 2
      responses in human allergic diseases. However, it is not clear how TSLP
      production by IECs is regulated in ulcerative colitis (UC), which appears to
      involve inflammatory Th2 responses. The aim of this study is to examine how TSLP
      production by IECs is regulated in ulcerative colitis. RESULTS: We show here that
      expression of TSLP was enhanced in mucosal lesions from UC patients in which
      inflammatory Th2 cytokine production was predominant. In addition, using a human
      colonic epithelial cell line, we demonstrated that a combination of tumor
      necrosis factor-alpha (TNF-alpha) and interleukin-4 (IL-4) induced TSLP
      expression and that TSLP expression by TNF-alpha + IL-4 was further enhanced by
      either Toll-like receptor 3 ligand or interferon (IFN)-gamma. CONCLUSIONS: Taken
      together, as in human allergic diseases, an inflammatory Th2 condition in the
      mucosal lesions of UC patients may trigger increased TSLP expression by IECs,
      resulting in exacerbation of UC.

PMID- 19757043
TI  - Adipokines and cytokines in human pancreatic juice: unraveling the local
      pancreatic inflammatory milieu.
AB  - BACKGROUND: Differential adipokine expression in obesity influences the
      inflammatory milieu, and may explain in part obesity's negative impact on
      pancreatic disease. Pancreatic juice analysis may provide a good means to
      evaluate the local pancreatic inflammatory milieu. The presence of adipokines in
      pancreatic juice is unknown. AIMS: This proof-of-concept study was designed to
      determine the presence of adipokines and cytokines in human pancreatic juice.
      METHODS: With institutional review board approval, pancreatic juice was obtained
      from ten patients with a broad range of diagnoses at the time of endoscopic
      retrograde cholangiopancreatography. Pancreatic juice was assayed using enzyme
      linked immunosorbent assay (ELISA) for insulin, the proinflammatory adipokine
      leptin, the anti-inflammatory adipokine adiponectin, and the inflammatory
      mediators interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and
      monocyte chemoattractant protein-1 (MCP-1). Correlation between adipokine and
      inflammatory mediator expression was determined by linear regression analysis.
      Data are presented as mean +/- standard error of the mean (SEM); P < 0.05 was
      considered statistically significant. RESULTS: Leptin (0.16 +/- 0.05 ng/ml) and
      adiponectin (0.63 +/- 0.02 microg/ml) were both present, as were the inflammatory
      mediators IL-6 (112.6 +/- 28.1 pg/ml), TNF-alpha (49.0 +/- 18.8 pg/ml), and MCP-1
      (32.2 +/- 0.9 pg/ml). Paradoxically, the expression of the anti-inflammatory
      adipokine adiponectin correlated strongly with that of the proinflammatory
      cytokine IL-6 (R(2) = 0.98, P < 0.001). CONCLUSIONS: This report is the first to
      describe adipokine expression in human pancreatic juice. Human pancreatic juice
      inflammatory mediators and adipokines may provide an important measurement of the
      local pancreatic inflammatory milieu.

PMID- 19757044
TI  - A functional SNP of the Interleukin-18 gene is associated with the presence of
      hepatocellular carcinoma in hepatitis B virus-infected patients.
AB  - BACKGROUND/AIM: The natural course of hepatitis B virus (HBV) infection is likely
      related to host immune factors. Interleukin-18 (IL-18) plays a significant role
      in immune defense. This study was undertaken to determine the association between
      the presence of hepatocellular carcinoma (HCC) and single-nucleotide
      polymorphisms (SNPs) in the IL-18 gene in HBV-infected patients. METHODS: Between
      March 2002 and December 2004, 730 Korean subjects were enrolled in two different
      groups: (1) chronic carrier without HCC (n=637) and (2) HCC (n=93). We analyzed
      SNPs at four polymorphic sites in the IL-18 gene at positions -667G>T, -148G>C,
      +8925C>G, and +13925A>C in the study subjects. To evaluate the functional
      significance of SNPs in the IL-18 gene promoter region, we performed a reporter
      gene assay in HepG2 and Hep3B cells transfected with different alleles. RESULTS:
      The IL-18 -148C allele, +8925G allele, +13925C allele, and haplotype 3 (TCGC)
      were associated with the presence of HCC in codominant and dominant models.
      Furthermore, functional analyses using the reporter gene assay revealed that the 
      148C allele conferred significantly lower promoter activity. CONCLUSIONS: This
      study indicates that the -148C, +8925G, and +13925C alleles of the IL-18 gene are
      associated with the presence of HCC and the 148G>C SNP is functionally important
      in determining disease outcome.

PMID- 19757045
TI  - Reduction in neutrophil count during hepatitis C treatment: drug toxicity or
      predictor of good response?
AB  - BACKGROUND: Bone marrow suppression is a well-recognized toxicity of the
      treatment of hepatitis C virus (HCV). Reduction of the peginterferon dose because
      of neutropenia is common in clinical practice. However, reduction of
      peginterferon dose during the first weeks of HCV treatment is associated with
      failure to achieve sustained virological response. AIMS: The objective of this
      study is to investigate whether the fall of neutrophil count during hepatitis C
      treatment is associated with achieving sustained virological response. METHODS:
      We performed an observational study of patients who completed peginterferon and
      ribavirin treatment in an Infectious Diseases Department in Manchester, UK.
      RESULTS: Of the 74 patients included in the analysis, 78% had genotype 2 or 3
      hepatitis C and 15% had liver cirrhosis. Sustained virological response was
      achieved in 78% of patients. On univariate analysis, factors related to achieving
      sustained virological response were younger age, genotype 2 or 3, baseline
      neutrophil count, and fall of neutrophil count during treatment. Multivariate
      analysis showed baseline neutrophil count >3.5 x 10(3) cells/mm(3) [odds ratio
      (OR) 5.7; 95% confidence interval (CI) 1.24-26.3] and a reduction of neutrophil
      count >60% (OR 4.5; 95% CI 1.03-19.9) to be independently associated with
      achieving sustained virological response. Neutropenia was not associated with an
      increased risk of infections. CONCLUSIONS: In this observational study, higher
      baseline neutrophil count and fall of neutrophil count during the treatment of
      hepatitis C was associated with achieving sustained virological response. These
      findings could have important implications for the monitoring and management of
      HCV treatment with peginterferon if they are confirmed in other studies.

PMID- 19757046
TI  - Hereditary hemorrhagic telangiectasia of the liver complicated by ischemic bile
      duct necrosis and sepsis: case report and review of the literature.

PMID- 19757047
TI  - Expression of VEGF, EGFR, and IL-6 in gastric adenomas and adenocarcinomas by
      endoscopic submucosal dissection.
AB  - BACKGROUND: The degree of intratumoral microvascular density is thought to affect
      tumor metastasis and prognosis in various human cancers, including gastric
      cancer. Despite recent medical advancements, gastric adenoma or adenocarcinoma
      remains a considerable therapeutic challenge. Endoscopic submucosal dissection
      (ESD) is a more recent approach that is now commonly used for radical resection
      of gastric adenoma and adenocarcinoma. AIM AND METHODS: The expression of
      vascular endothelial growth factor (VEGF), epidermal growth factor receptor
      (EGFR), and interleukin-6 (IL-6) are related to the prognosis of gastric
      adenocarcinoma. However, the expression of these factors in gastric
      adenoma/adenocarcinoma following ESD has not been clearly evaluated. Here, we
      report on our study of the expression of VEGF, EGFR, and IL-6 by
      immunohistochemical staining in extracted tissue from adenoma or adenocarcinoma
      of the stomach by ESD and subsequent evaluation of the correlation of VEGF, EGFR,
      and IL-6 with other clinicopathological parameters. The patient cohort consisted
      of 102 patients with adenoma or adenocarcinoma of the stomach. RESULTS:
      Immunohistochemical staining for VEGF and IL-6 was significantly higher in both
      high grade dysplasia and adenocarcinoma than in low grade dysplasia (P < 0.05).
      There was significant correlation between histological grade and intensity of
      immunohistochemical staining of VEGF (P = 0.039). Histological differentiation of
      adenocarcinoma was related to IL-6 expression (P = 0.028). The immunoreactivity
      of VEGF and IL-6 increased significantly in lesions >2 cm compared to lesions <2
      cm (P < 0.05). CONCLUSION: The immunohistochemical expression of IL-6 and VEGF
      can be considered to be useful for clinical diagnosis and follow-up of adenoma or
      adenocarcinoma of the stomach.

PMID- 19757048
TI  - Chemoprevention of colonic polyps with balsalazide: an exploratory, double-blind,
      placebo-controlled study.
AB  - BACKGROUND: A number of agents, including aspirin, nonsteroidal antiinflammatory
      drugs, cyclooxygenase-2 inhibitors, folic acid, calcium, and vitamins, have been
      evaluated for their potential in chemoprevention of sporadic colorectal adenomas
      or cancer. Preclinical data suggest that 5-aminosalicylates also may have a
      chemopreventive effect. AIM: To investigate chemoprevention of colonic polyps
      with balsalazide, a 5-aminosalicylate prodrug. METHODS: In this randomized,
      double-blind, placebo-controlled study, adults diagnosed with small polyps in the
      rectosigmoid colon were treated with either balsalazide 3 g/d or placebo for 6
      months. Follow-up lower endoscopy was performed, and all polyps were measured and
      analyzed histologically. The primary endpoint was reduction in mean size of the
      largest polyp per subject. RESULTS: Among 241 participants screened, 86 were
      randomized to treatment, with 75 subjects evaluable. Balsalazide 3 g/d (n = 38)
      did not significantly reduce the mean size of the largest colonic polyp or the
      number of polyps compared with placebo (n = 37). Although not significant, post
      hoc analysis revealed that total adenoma burden per subject, calculated as the
      sum of the volumes of all adenomas in mm3, increased by 55% in the balsalazide
      group compared with 95% in the placebo group. CONCLUSIONS: Although balsalazide
      did not have significant chemopreventive effects on established colonic polyps,
      these results can aid in designing future prospective studies.

PMID- 19757049
TI  - Outcome of colonoscopy in elderly African-American patients.
AB  - BACKGROUND: Average-risk individuals should be offered a screening colonoscopy
      beginning at 50 years of age. However, there is no clear consensus on an age at
      which patients should no longer be offered a screening colonoscopy. The purpose
      of this study was to analyze the outcome of colonoscopy in elderly individuals
      based on the preprocedure indication. METHODS: A retrospective chart review was
      performed of all patients who underwent colonoscopy at Howard University Hospital
      from Jan 1, 2001 to Dec 31, 2005. Patients older than age 75 years were then
      stratified into two groups: one group classified as average risk for colon cancer
      and a second group classified as higher risk for finding cancer based on
      indication. Significant findings from colonoscopy were assigned if the patient
      was found to have an advanced adenoma, such as villous attributes, high-grade
      dysplasia, adenoma C1 cm, or cancer. All others findings at colonoscopy were
      categorized as having nonsignificant findings. RESULTS: During this period, 922
      elderly patients (75 years of age or older) underwent colonoscopy. Based on
      preprocedure indications, 606 patients were considered higher risk and 316
      average risk. Among the preprocedure higher-risk patients, 532 had nonsignificant
      findings include hemorrhoids, diverticulosis, telangiectasias, lipomas, and
      inflammatory polyps. Among the preprocedure average-risk patients, 286 had
      nonsignificant findings. From the 110 patients who underwent screening
      colonoscopy, 99 patients had nonsignificant findings. Malignancy was found in 42
      patients: 33 who had higher-risk indications and 9 who had average-risk
      indications. CONCLUSION: Average-risk patients are less likely to have
      significant findings, including cancer, on colonoscopy.

PMID- 19757050
TI  - Suppurative (phlegmonous) gastritis presenting as a gastric mass.

PMID- 19757051
TI  - Hydrogen peroxide improves the visibility of ulcer bases in acute non-variceal
      upper gastrointestinal bleeding: a single-center prospective study.
AB  - BACKGROUND: Acute non-variceal upper gastrointestinal bleeding (ANVB) or
      hemorrhage (used interchangeably) is an emergency. Endoscopically applied
      hydrogen peroxide (H2O2) has been shown to improve visualization of the ulcer
      base. AIMS: To test the hypothesis that ulcer base clot clearance with 3% H2O2
      improves the visualization of ANVB lesions compared to water alone. METHODS: In
      this single-center prospective study, 320 patients with ANVB were examined, of
      which 81 met the entry criteria for evaluation. All patients with ANVB underwent
      urgent endoscopy. Those with adherent clots on the ulcer base were sprayed with
      250 ml of water, followed by up to 100 ml of 3% H2O2. The main outcome
      measurement was Kalloo"s Visual Scores of the ulcer base before and after water
      and H2O2. RESULTS: Eighty-one patients with gastric ulcers (GU; 34) and duodenal
      ulcers (DU; 47) met the entry criteria. The mean improvement in grade from water
      to H2O2 was 2.04 (95% confidence interval [CI] (1.86, 2.23)). The mean volume of
      H2O2 used to clear clots was higher (70 ml) in patients who were negative for
      both Helicobacter pylori and non-steroidal anti-inflammatory drug (NSAID) use
      than in those who were positive for both (31 ml) (P = 0.00). More DU patients
      (72%) had visible vessels than GU patients (44%) (P = 0.01). CONCLUSIONS: H2O2
      improved the visualization of ulcer bases in ANVB. A smaller volume of H2O2 was
      required to clear clots in patients who used NSAIDs and had H. pylori infection.
      H2O2 identified more DU vessels. The use of H2O2 should be considered as a
      standard therapy in the management of clots in ANVB.

PMID- 19757052
TI  - The Project Towards No Drug Abuse (TND) dissemination trial: implementation
      fidelity and immediate outcomes.
AB  - One of the important research issues in the emerging area of research on
      dissemination of prevention programs relates to the type and extent of training
      needed by program providers to prepare them to implement effective programs with
      fidelity. The present paper describes the immediate outcomes of a dissemination
      and implementation trial of Project Toward No Drug Abuse, an evidence-based
      prevention program for high school students. A total of 65 high schools in 14
      school districts across the USA were recruited and randomly assigned to one of
      three experimental conditions: comprehensive implementation support for teachers,
      regular workshop training only, or standard care control. The comprehensive
      intervention was comprised of on-site coaching, web-based support, and technical
      assistance, in addition to the regular workshop. Students (n = 2,983) completed
      self-report surveys before and immediately after program implementation. Fidelity
      of implementation was assessed with a classroom observation procedure that
      focused on program process. Results indicated that relative to the controls, both
      intervention conditions produced effects on hypothesized program mediators,
      including greater gains in program-related knowledge; greater reductions in
      cigarette, marijuana and hard drug use intentions; and more positive changes in
      drug-related beliefs. There were stronger effects on implementation fidelity in
      the comprehensive, relative to the regular, training condition. However, seven of
      the ten immediate student outcome measures showed no significant differences
      between the two training conditions. The implications of these findings for
      dissemination research and practice are discussed.

PMID- 19757054
TI  - Indicators of acculturation related to Somali refugee women's birth outcomes in
      Minnesota.
AB  - We investigated the effect of indicators of acculturation among Somali refugee
      women's birth outcomes. Data were extracted from medical records of 584 Somali
      women delivering infants at a Midwestern hospital between 1993 and 2006.
      Bivariate analyses measured relationships between independent factors and the
      dependent variables of gestational age and birthweight. Structural equation
      modeling (SEM) determined the fit between factors hypothesized to reflect
      acculturation and the data. Significant increases noted over time were substance
      use/exposure, interpreter use, body mass index, hemoglobin levels, gestational
      diabetes and preterm birth. Bivariate analyses showed significance between
      prenatal care utilization and both preterm birth and gestational age. SEM results
      indicated a moderate to good fit between the hypothesized model and available
      data. Factors hypothesized to reflect acculturation and effect birth outcomes
      among Somali women are increasing but did not account for increased preterm
      birth. Further investigation is warranted to identify and truncate further
      disparate birth outcomes.

PMID- 19757055
TI  - Risk factors for obesity and high blood pressure in Chinese American children:
      maternal acculturation and children's food choices.
AB  - The objective of this study is to explore risk factors associated with overweight
      and high blood pressure in Chinese American children. Students and their parents
      were recruited from Chinese language schools in the San Francisco Bay Area. Data
      were collected on 67 children and their mothers, and included children's weight,
      height, waist and hip circumferences, blood pressure, level of physical activity,
      dietary intake, usual food choice, knowledge about nutrition and physical
      activity, and self-efficacy regarding diet and physical activity. Mothers
      completed questionnaires on demographic data and acculturation. About 46% of
      children had a body mass index exceeding the 85th percentile. Lower level of
      maternal acculturation is a risk factor for overweight and higher waist to hip
      ratio. Children's unhealthy food choices were predictive of high body mass index
      and high systolic blood pressure, whereas older age and less physical activity in
      children were predictors of high diastolic blood pressure. Developing culturally
      sensitive and developmentally appropriate interventions to reduce overweight and
      high blood pressure is critical to reduce health disparities among minority
      children.

PMID- 19757056
TI  - The feasibility of irreversible electroporation for the treatment of breast
      cancer and other heterogeneous systems.
AB  - Developments in breast cancer therapies show potential for replacing simple and
      radical mastectomies with less invasive techniques. Localized thermal techniques
      encounter difficulties, preventing their widespread acceptance as replacements
      for surgical resection. Irreversible electroporation (IRE) is a non-thermal,
      minimally invasive focal ablation technique capable of killing tissue using
      electric pulses to create irrecoverable nano-scale pores in the cell membrane.
      Its unique mechanism of cell death exhibits benefits over thermal techniques
      including rapid lesion creation and resolution, preservation of the extracellular
      matrix and major vasculature, and reduced scarring. This study investigates
      applying IRE to treat primary breast tumors located within a fatty extracellular
      matrix despite IREs dependence on the heterogeneous properties of tissue. In
      vitro experiments were performed on MDA-MB-231 human mammary carcinoma cells to
      determine a baseline electric field threshold (1000 V/cm) to cause IRE for a
      given set of pulse parameters. The threshold was incorporated into a three
      dimensional numerical model of a heterogeneous system to simulate IRE treatments.
      Treatment-relevant protocols were found to be capable of treating targeted tissue
      over a large range of heterogeneous properties without inducing significant
      thermal damage, making IRE a potential modality for successfully treating breast
      cancer. Information from this study may be used for the investigation of other
      heterogeneous tissue applications for IRE.

PMID- 19757057
TI  - Log energy entropy-based EEG classification with multilayer neural networks in
      seizure.
AB  - In this study, normal EEG series recorded from healthy volunteers and epileptic
      EEG series recorded from patients within and without seizure are classified by
      using Multilayer Neural Network (MLNN) architectures with respect to several time
      domain entropy measures such as Shannon Entropy (ShanEn), Log Energy Entropy
      (LogEn), and Sample Entropy (Sampen). In tests, the MLNN is performed with
      several numbers of neurons for both one hidden layer and two hidden layers. The
      results show that segments in seizure have significantly lower entropy values
      than normal EEG series. This result indicates an important increase of EEG
      regularity in epilepsy patients. The LogEn approach, which has not been
      experienced in EEG classification yet, provides the most reliable features into
      the EEG classification with very low absolute error as 0.01. In particular, the
      MLNN can be proposed to distinguish the seizure activity from the seizure-free
      epileptic series where the LogEn values are considered as signal features that
      characterize the degree of EEG complexity. The highest classification accuracy is
      obtained for one hidden layer architecture.

PMID- 19757058
TI  - Wall shear stress and pressure distribution on aneurysms and infundibulae in the
      posterior communicating artery bifurcation.
AB  - A growing number of cases of rupture at an infundibulum, progression of
      infundibulum to a frank aneurysm, and subarachnoid hemorrhage (SAH) in the
      posterior communicating artery (PCoA) have been reported. Using patient-specific
      geometric models of the supraclinoid internal carotid artery (ICA) with PCoA
      infundibulum or aneurysm, high-resolution computational fluid dynamics
      simulations were performed by solving the Navier-Stokes equations with a
      spectral/hp element method. Simulation results show that the flow impinges at the
      distal wall of infundibulum near the outside of the ICA bend and creates a region
      of higher pressure (4-5 mmHg) surrounded by a band of a high wall shear stress
      (WSS) (20-30 N/m(2) on average). At the proximal end of the infundibulum, another
      stagnation area is formed characterized by low WSS (<1 N/m(2)) and high
      oscillating shear index. This impingement region seems to coincide with the
      locations of the rupture of infundibulae or progression to aneurysms. In
      addition, the pulsatile flow becomes unstable due to the presence of aneurysms or
      aneurysm-like infundibulae, and this leads to WSS temporal fluctuations inside
      the aneurysm, which may accelerate the degenerative processes in the vessel
      walls.

PMID- 19757059
TI  - A conductivity approach to measuring fixed charge density in intervertebral disc
      tissue.
AB  - A new method for measuring the fixed charge density (FCD) in intervertebral disc
      (IVD) tissues employing a two-point electrical conductivity approach was
      developed. In this technique, the tissue is first confined and equilibrated in a
      potassium chloride (KCl) solution, and the tissue conductivity is then measured.
      This is then repeated with a second concentration of KCl solution. The FCD can be
      determined from the conductivity measurements. Using this method, the FCD values
      of bovine annulus fibrosus (AF) and nucleus pulposus (NP) tissues were determined
      to be 0.060 +/- 0.027 mEq/g wet tissue and 0.19 +/- 0.039 mEq/g wet tissue,
      respectively. The FCD of AF was significantly lower than that of NP tissue,
      similar to results in the literature for human IVD tissues. In order to verify
      the accuracy of the new method, the glycosaminoglycan (GAG) contents of the
      tissues were measured and used to estimate the tissue FCD. A strong correlation
      (R (2) = 0.84-0.87) was found to exist between FCD values measured and those
      estimated from GAG contents, indicating that the conductivity approach is a
      reliable technique for measuring the FCD of IVD tissues.

PMID- 19757060
TI  - Chondrogenesis and integration of mesenchymal stem cells within an in vitro
      cartilage defect repair model.
AB  - Integration of repair tissue is a key indicator of the long-term success of cell
      based therapies for cartilage repair. The objective of this study was to compare
      the in vitro chondrogenic differentiation and integration of agarose hydrogels
      seeded with either chondrocytes or bone marrow-derived mesenchymal stem cells
      (MSCs) in defects created in cartilage explants. Chondrocytes and MSCs were
      isolated from porcine donors, suspended in 2% agarose and then injected into
      cylindrical defects within the explants. These constructs were maintained in a
      chemically defined medium supplemented with 10 ng/mL of TGF-beta3. Cartilage
      integration was assessed by histology and mechanical push-out tests. After 6
      weeks in culture, chondrocyte-seeded constructs demonstrated a higher integration
      strength (64.4 +/- 8.3 kPa) compared to MSC-seeded constructs (22.7 +/- 5.9 kPa).
      Glycosaminoglycan (GAG) (1.27 +/- 0.3 vs. 0.19 +/- 0.03 kPa) and collagen (0.31
      +/- 0.08 vs. 0.09 +/- 0.01 kPa) accumulation in chondrocyte-seeded constructs was
      greater than that measured in the MSC-seeded group. The GAG, collagen, and DNA
      content of both chondrocyte- and MSC-seeded hydrogels cultured in cartilage
      explants was significantly lower than control constructs cultured in free
      swelling conditions. The results of this study suggest that the explant model may
      constitute a more rigorous in vitro test to assess MSC therapies for cartilage
      defect repair.

PMID- 19757061
TI  - Detecting mitoses in time-lapse images of embryonic epithelia using intensity
      analysis.
AB  - Although the frequency and orientation of mitoses can significantly affect the
      mechanics of early embryo development, these data have not been available due to
      a shortage of suitable automated techniques. Fluorescence imaging, though
      popular, requires biochemical intervention and is not always possible or
      desirable. Here, a new technique that takes advantage of a localized intensity
      change that occurs in bright field images is used to identify mitoses. The
      algorithm involves mapping a deformable, sub-cellular triangular mesh from one
      time-lapse image to the next so that corresponding regions can be identified.
      Triangles in the mesh that undergo darkening of a sufficient degree over a period
      consistent with mitosis are flagged. Mitoses are assumed to occur along the short
      axis of elliptical areas fit to suitably sized clusters of flagged triangles. The
      algorithm is less complex than previous approaches and it has strong
      discrimination characteristics. When applied to 15 image sets from neurulation
      stage axolotl (Ambystoma mexicanum) embryos, it was able to correctly detect 86%
      of the manually identified mitoses, had less than 5% false positives and produced
      average angular errors of only 15 degrees . The new algorithm is simpler to
      implement than those previously available, is substantially more accurate, and
      provides data that is important for understanding the mechanics of morphogenetic
      movements.

PMID- 19757062
TI  - Effect of eddy length scale on mechanical loading of blood cells in turbulent
      flow.
AB  - Non-physiological turbulent blood flow is known to occur in and near implanted
      cardiovascular devices, but its effects on blood are poorly understood. The
      objective of this work is to investigate the effect of turbulent eddy length
      scale on blood cell damage, and in particular to test the hypothesis that only
      eddies similar in size to blood cells can cause damage. The microscale flow near
      a red blood cell (RBC) in an idealized turbulent eddy is modeled computationally
      using an immersed boundary method. The model is validated for the special case of
      a tank-treading RBC. In comparisons between turbulent flow fields, based on
      Kolmogorov theory, the model predicts that damage due to the smallest eddies is
      almost independent of the Kolmogorov length scale. The model predicts that within
      a given flow field, however, eddies of sub-cellular scale are less damaging than
      larger eddies. Eddy decay time and the turbulent energy spectral density are
      highlighted as important factors. The results suggest that Kolmogorov scale is
      not an adequate predictor of flow-induced blood trauma, and highlights the need
      for deeper understanding of the microscale structure of turbulent blood flow.

PMID- 19757063
TI  - Endoplasmic reticulum stress-induced apoptosis  in the development of diabetes:
      is there a role  for adipose tissue and liver?
AB  - Diabetes mellitus (DM) is a multifactorial chronic metabolic disease
      characterized by hyperglycaemia. Several different mechanisms have been
      implicated in the development of the disease, including endoplasmic reticulum
      (ER) stress. ER stress is increasingly acknowledged as an important mechanism in
      the development of DM, not only for beta-cell loss but also for insulin
      resistance. Accumulating evidence suggests that ER stress-induced apoptosis may
      be an important mode of beta-cell loss and therefore important in the development
      of diabetes. Recent data also suggest a role of ER stress-induced apoptosis in
      liver and adipose tissue in relation to diabetes, but more extensive studies on
      human adipocyte and hepatocyte (patho)physiology and ER stress are needed to
      identify the exact interactions between environmental signals, ER stress and
      apoptosis in these organs.

PMID- 19757064
TI  - Up-regulation of GADD45alpha expression by NSAIDs leads to apoptotic and necrotic
      colon cancer cell deaths.
AB  - Growth arrest and DNA damage inducible 45 alpha (GADD45alpha) is a central player
      in mediating apoptosis induced by a variety of stress stimuli and genotoxic
      agents. Regular usage of nonselective nonsteroidal anti-inflammatory drugs
      (NSAIDs) such as indomethacin and sulindac is associated with reduced risk for
      various cancers, including colon cancer. The role of GADD45alpha in NSAID-induced
      colon cancer cell cytotoxicity is unknown. In this study, we report that
      indomethacin and sulindac sulfide treatments up-regulate GADD45alpha mRNA
      expression and protein levels in colon cancer HT-29, RKO and Caco-2 cells. This
      up-regulation of GADD45alpha is accompanied by necrotic cell death and apoptosis.
      Anti-sense suppression of GADD45alpha expression inhibited indomethacin and
      sulindac sulfide-induced necrotic cell death and apoptosis. These findings
      confirm a role for GADD45alpha in NSAID-induced cytotoxicity, a mechanism for the
      anti-neoplastic effect of NSAIDs in colon tumorigenesis and cancer growth.

PMID- 19757065
TI  - Activation of Akt/GSK-3beta signaling pathway is involved in intermedin(1-53)
      protection against myocardial apoptosis induced by ischemia/reperfusion.
AB  - Intermedin (IMD) is a novel member of the calcitonin/calcitonin gene-related
      peptide family. We investigated the cardioprotective mechanism of IMD(1-53) in
      the in vivo rat model of myocardial ischemia/reperfusion (I/R) injury and in
      vitro primary neonatal cardiomyocyte model of hypoxia/reoxygenation (H/R).
      Myocardial infarct size was measured by 2,3,5-triphenyl tetrazolium chloride
      staining. Cardiomyocyte viability was determined by trypan blue staining, cell
      injury by lactate dehydrogenase (LDH) leakage, and cardiomyocyte apoptosis by
      terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling assay,
      Hoechst staining, gel electrophoresis and caspase 3 activity. The translocation
      of mitochondrial cytochrome c of myocardia and expression of apoptosis-related
      factors Bcl-2 and Bax, phosphorylated Akt and phosphorylated GSK-3beta were
      determined by western blot analysis. IMD(1-53) (20 nmol/kg) limited the
      myocardial infarct size in rats with I/R; the infarct size was decreased by 54%,
      the apoptotic index by 30%, and caspase 3 activity by 32%; and the translocation
      of cytochrome c from mitochondria to cytosol was attenuated. IMD(1-53) increased
      the mRNA and protein expression of Bcl-2 and ratio of Bcl-2 to Bax by 81 and
      261%, respectively. IMD(1-53) (1 x 10(-7) mol/L) inhibited the H/R effect in
      cardiomyocytes by reducing cell death by 43% and LDH leakage by 16%; diminishing
      cellular apoptosis; decreasing caspase 3 activity by 50%; and increasing the
      phosphorylated Akt and GSK-3beta by 41 and 90%, respectively. The cytoprotection
      of IMD(1-53) was abolished with LY294002, a PI3K inhibitor. In conclusion, IMD(1
      53) exerts cardioprotective effect against myocardial I/R injury through the
      activation of the Akt/GSK-3beta signaling pathway to inhibit mitochondria
      mediated myocardial apoptosis.

PMID- 19757066
TI  - Serum deprivation induced autophagy and predominantly an AIF-dependent apoptosis
      in hippocampal HT22 neurons.
AB  - Neuronal death induced by serum deprivation (SD) in HT22-cells was accompanied by
      a moderate activation of caspase-3, a prominent upregulation of AIF and its
      translocation into the nucleus. In addition protein levels of autophagy markers
      such as LC3 and beclin-1 were affected by SD. The ratio of LC3-II/LC3-I was
      significantly increased in serum deprived cultures. Furthermore, the addition of
      the pan-caspase inhibitor z-VAD(OMe)-FMK (zVAD) does not protect HT22-cells from
      SD-induced neurodegeneration. However, addition of the autophagy inhibitors such
      as 3-methyladenine (3-MA) or bafilomycin A1 (BafA1) provided a potentiation of
      cell death induced by SD. z-VAD and 3-MA in combination were not only ineffective
      in rescuing cells from the damaging effects of SD, but seem likely to act in
      synergy to potentiate slightly SD-induced cell death. The results of the current
      study suggest that SD induced predominantly caspase-independent apoptosis in
      hippocampal HT22 cells and that inhibition of autophagy is rather deleterious
      than protective.

PMID- 19757067
TI  - Geographical location has greater impact on carotenoid content and
      bioaccessibility from tomatoes than variety.
AB  - The suggested health benefits of consuming tomatoes and tomato-based products
      have been attributed, in part, to the carotenoids present in these foods.
      Therefore, the objectives of the present study were to (i) analyse carotenoid
      content and bioaccessibility from different tomato (Lycopersicon esculentum L.)
      types namely cherry, plum, round, and certain tomatoes-on-the-vine; and (ii)
      determine if geographical location (Ireland vs Spain) influenced the content and
      bioaccessibility of carotenoids in tomatoes of the same variety. Carotenoid
      bioaccessibility is defined as the amount of ingested carotenoids that, after
      digestion, are available for absorption by intestinal cells. Differences were
      seen in carotenoid content and bioaccessibility between the different tomato
      types tested. For instance, Irish round high-lycopene tomatoes contained the
      greatest amounts of lycopene and lutein but lowest levels of beta-carotene
      compared with the other Irish tomatoes. Furthermore, the content and
      bioaccessibility of carotenoids that were sourced from Ireland and Spain also
      varied greatly. Spanish tomatoes were generally superior in the content,
      bioaccessibility, and micelle content of carotenoids. To conclude, our findings
      suggest that geographical location, rather than the type of tomato, seems to have
      a more pronounced effect on carotenoid bioaccessibility from tomatoes.

PMID- 19757068
TI  - Characterization of cell wall polysaccharides of cherry (Prunus cerasus var.
      Schattenmorelle) fruit and pomace.
AB  - The polysaccharide composition of cell wall of sour cherry (Prunus cerasus var.
      Schattenmorelle) fruit and pomace was investigated. Furthermore, the alcohol
      insoluble solids composition of 'Kelleriis' and 'Dobreczyn Botermo' varieties
      were studied too. Yield of alcohol insoluble solids for fruits was lower than
      10%, and for pomaces circa 50%. Uronic acid was the main pectin component of
      alcohol insoluble solids. Enzymes used as juice processing aids decreased the
      content of uronic acid. Araban and galactan side chains bonded tightly to
      cellulose presence was suggested by high content of arabinose and galactose in
      hemicellulose fraction. The process of drying at below 70 degrees C did not
      influence polysaccharide composition of sour cherry pomaces. Alcohol insoluble
      solids of fruits expressed higher hydration properties than of pomaces.

PMID- 19757070
TI  - Electroporation based on hydrodynamic focusing of microfluidics with low dc
      voltage.
AB  - Microfluidics-based cell electroporation has many advantages in delivering small
      molecules into cells. In this study, hydrodynamic focusing of fluids with
      different conductivities has been used for high through-put cell electroporation
      at low voltage (<3 V) of continuous direct current (dc) power. Simulation results
      showed that an input voltage of only 1.5 V could generate an electric field
      intensity of about 1.17 kV cm(-1) across the cell suspension flow in the squeezed
      area. The electropermeation of yeast cell was observed, showing a
      permeabilization percentage up to 70%.

PMID- 19757069
TI  - Microtube-based electrode arrays for low invasive extracellular recording with a
      high signal-to-noise ratio.
AB  - We report on the development of a microtube electrode array as a neural interface
      device. To combine the desired properties for the neural interface device, such
      as low invasiveness with a small needle and a good signal-to-noise ratio in
      neural recordings, we applied the structure of a glass pipette electrode to each
      microtube electrode. The device was fabricated as sub-5-microm-diameter out-of
      plane silicon dioxide microtube arrays using silicon microneedle templates, which
      are grown by the selective vapor-liquid-solid method. The microtubes had inner
      diameters of 1.9-6.4 microm and a length of 25 microm. Impedances ranged from 220
      kOmega to 1.55 MOmega, which are less than those for conventional microneedles.
      In addition, the microtube electrodes had less signal attenuation than
      conventional microneedle electrodes. We confirmed that the effects of parasitic
      capacitances between neighboring microtubes and channels were sufficiently small
      using a test signal. Finally, neural responses evoked from a rat peripheral nerve
      were recorded in vivo using a microtube electrode to confirm that this type of
      electrode can be used for both electrophysiological measurements and as a neural
      interface device.

PMID- 19757071
TI  - Targeted cell adhesion on selectively micropatterned polymer arrays on a
      poly(dimethylsiloxane) surface.
AB  - Herein, we introduce the fabrication of polymer micropattern arrays on a
      chemically inert poly(dimethylsiloxane) (PDMS) surface and employ them for the
      selective adhesion of cells. To fabricate the micropattern arrays, a mercapto
      ester-based photocurable adhesive was coated onto a mercaptosilane-coated PDMS
      surface and photopolymerized using a photomask to obtain patterned arrays at the
      microscale level. Robust polymer patterns, 380 microm in diameter, were
      successfully fabricated onto a PDMS surface, and cells were selectively targeted
      toward the patterned regions. Next, the performance of the cell adhesion was
      observed by anchoring cell adhesive linker, an RGD oligopeptide, on the surface
      of the mercapto-ester-based adhesive-cured layer. The successful anchoring of the
      RGD linker was confirmed through various surface characterizations such as water
      contact angle measurement, XPS analysis, FT-IR analysis, and AFM measurement. The
      micropatterning of a photocurable adhesive onto a PDMS surface can provide high
      structural rigidity, a highly-adhesive surface, and a physical pathway for
      selective cell adhesion, while the incorporated polymer micropattern arrays
      inside a PDMS microfluidic device can serve as a microfluidic platform for
      disease diagnoses and high-throughput drug screening.

PMID- 19757072
TI  - Microfluidic gradient PCR (MG-PCR): a new method for microfluidic DNA
      amplification.
AB  - This study develops a new microfluidic DNA amplification strategy for executing
      parallel DNA amplification in the microfluidic gradient polymerase chain reaction
      (MG-PCR) device. The developed temperature gradient microfluidic system is
      generated by using an innovative fin design. The device mainly consists of
      modular thermally conductive copper flake which is attached onto a finned
      aluminum heat sink with a small fan. In our microfluidic temperature gradient
      prototype, a non-linear temperature gradient is produced along the gradient
      direction. On the copper flake of length 45 mm, width 40 mm and thickness 4 mm,
      the temperature gradient easily spans the range from 97 to 52 degrees Celsius. By
      making full use of the hot (90-97 degrees Celsius) and cold (60-70 degrees
      Celsius) regions on the temperature gradient device, the parallel, two
      temperature MG-PCR amplification is feasible. As a demonstration, the MG-PCR from
      three parallel reactions of 112-bp Escherichia coli DNA fragment is performed in
      a continuous-flow format, in which the flow of the PCR reagent in the closed loop
      is induced by the buoyancy-driven nature convection. Although the prototype is
      not optimized, the MG-PCR amplification can be completed in less than 45 min.
      However, the MG-PCR thermocycler presented herein can be further scaled-down, and
      thus the amplification times and reagent consumption can be further reduced. In
      addition, the currently developed temperature gradient technology can be applied
      onto other continuous-flow MG-PCR systems or used for other analytical purposes
      such as parallel and combination measurements, and fluorescent melting curve
      analysis.

PMID- 19757073
TI  - A self-contained fully-enclosed microfluidic cartridge for lab on a chip.
AB  - We describe a self-contained fully-enclosed cartridge for lab-on-a-chip
      applications where sample and reagents can be applied sequentially as is
      performed in a heterogeneous immunoassay, or nucleic acid extraction. Both the
      self-contained and fully-enclosed features of the cartridge are sought to ensure
      its safe use in the field by unskilled staff. Simplicity in cartridge design and
      operation is obtained via adopting a valveless concept whereby reagents are
      stored and used in the form of liquid plugs isolated by air spacers around a
      fluidic loop. Functional components integrated in the loop include a microfluidic
      chip specific to the target application, a novel peristaltic pump to displace the
      liquid plugs, and a pair of removable tubing segments where one is used to
      introduce biological sample and while the other is to collect eluant. The novel
      pump is fabricated through soft-lithography technique and works by pinching a
      planar channel under stainless-steel ball bearings that have been magnetically
      loaded. The utility of the cartridge is demonstrated for automated extraction and
      purification of nucleic acids (DNA) from a cell lysate on a battery-operated
      portable system. The cartridge shown here can be further extended to sample-in
      answer-out diagnostic tests.

PMID- 19757074
TI  - Triangular neuronal networks on microelectrode arrays: an approach to improve the
      properties of low-density networks for extracellular recording.
AB  - Multi-unit recording from neuronal networks cultured on microelectrode arrays
      (MEAs) is a widely used approach to achieve basic understanding of network
      properties, as well as the realization of cell-based biosensors. However, network
      formation is random under primary culture conditions, and the cellular
      arrangement often performs an insufficient fit to the electrode positions. This
      results in the successful recording of only a small fraction of cells. One
      possible approach to overcome this limitation is to raise the number of cells on
      the MEA, thereby accepting an increased complexity of the network. In this study,
      we followed an alternative strategy to increase the portion of neurons located at
      the electrodes by designing a network in confined geometries. Guided settlement
      and outgrowth of neurons is accomplished by taking control over the adhesive
      properties of the MEA surface. Using microcontact printing a triangular two
      dimensional pattern of the adhesion promoter poly-D-lysine was applied to the MEA
      offering a meshwork that at the same time provides adhesion points for cell
      bodies matching the electrode positions and gives frequent branching points for
      dendrites and axons. Low density neocortical networks cultivated under this
      condition displayed similar properties to random networks with respect to the
      cellular morphology but had a threefold higher electrode coverage. Electrical
      activity was dominated by periodic burst firing that could pharmacologically be
      modulated. Geometry of the network and electrical properties of the patterned
      cultures were reproducible and displayed long-term stability making the
      combination of surface structuring and multi-site recording a promising tool for
      biosensor applications.

PMID- 19757075
TI  - Context-dependent dynamic processes in attention deficit/hyperactivity disorder:
      differentiating common and unique effects of state regulation deficits and delay
      aversion.
AB  - The ability to specify differential predictions is a mark of a scientific models'
      value. State regulation deficits (SRD) and delay aversion (DAv) have both been
      hypothesized as context-dependent dynamic dysfunctions in ADHD. However, to date
      there has been no systematic comparison of their common and unique elements. Here
      we review these hypotheses-and describe the core and secondary manifestations of
      the two constructs and review evidence in support of them. Second, we focus on
      what are seen as the hallmark indicators of the two deficits-preference of small
      immediate over large delayed rewards for DAv and the slow event rate effect for
      SRD. We describe the overlap between these two manifestations and then explore
      how experimental manipulations and the analysis of neuropsychological and
      physiological mediators of effects can allow us to differentiate these two
      patterns of neuropsychological dysfunction on the basis of specific predictions.
      Finally, we highlight the implications of neuropsychological heterogeneity for
      the practical implementation of tests of DAv and SRD.

PMID- 19757076
TI  - The distribution and frequency of seclusion and/or restraint among psychiatric
      inpatients.
AB  - This paper reports on the frequency and distribution of seclusion or restraint
      (SR) episodes among 1,266 adult inpatients at a state psychiatric hospital during
      the 2004 calendar year. Data on the concentration of SR episodes over patients
      and time can assist in planning alternative, recovery-oriented treatment models.
      Fifteen percent (N = 194) of patients experienced seclusion or restraint. Sixty
      three percent of all seclusion hours were concentrated among only ten patients.
      Likewise, the ten patients with the most restraint hours constituted nearly 65%
      of total restraint hours for the year and 48% of all restraint episodes.
      Variables accessible through administrative data accounted for modest seclusion
      and restraint variance. A comprehensive strategy to prevent SR episodes requires
      tailored interventions targeted to known high-risk individuals and development of
      general hospital-wide alternatives to SR. General alternatives require greater
      attention to staff education, administrative oversight, de-escalation and
      debriefing practices, patient involvement, and other recovery-oriented practices
      to reduce or eliminate use of seclusion and restraint.

PMID- 19757077
TI  - Defining larger roles for "tiny" RNA molecules: role of miRNAs in
      neurodegeneration research.
AB  - Many facets of transcriptional and translational regulation contribute to the
      proper functioning of the nervous system. Dysfunctional control of mRNA and
      protein expression can lead to neurodegenerative conditions. Recently, a new
      regulatory control element--small noncoding RNAs--has been found to play a
      significant role in many physiologic systems. Here, we review the microRNA
      (miRNA) field as it pertains to discovery-based and mechanistic studies on the
      brain and specifically in neurodegenerative disorders. Understanding the role of
      miRNAs in the brain will aid to open new avenues to the field of neuroscience
      and, importantly, neurodegenerative disease research.

PMID- 19757078
TI  - Identification of transcription start sites and preferential expression of select
      CB2 transcripts in mouse and human B lymphocytes.
AB  - Marijuana cannabinoids, the endocannabinoids, and cannabinoid cell receptors have
      been shown to play important roles in immune regulation particularly as potent
      modulators of anti-inflammatory cytokines. The predominant cannabinoid receptor
      involved in this immune regulation is cannabinoid receptor 2 (CB(2)), which is
      predominantly expressed in B lymphocytes. However, the promoter region and
      mechanisms of CB(2) gene regulation are unknown in this immune cell type.
      Utilizing a combination of bioinformatics, 5' rapid amplification of cDNA ends
      (5' RACE), real-time reverse transcription-polymerase chain reaction, DNA
      sequencing, and luciferase reporter assays, we show that human B cells express
      one CB(2) transcript while mouse B cells express three CB(2) transcripts, with
      specific transcript selection occurring during B cell activation by
      lipopolysaccharide. Alignment of our sequenced RACE products to either the mouse
      or human genome, along with the GenBank submitted mRNA sequences, revealed that
      the transcripts we isolated contained previously unidentified transcriptional
      start sites (TSS). In addition, expression construct testing of the genomic
      region containing the TSSs of the mouse CB(2) exon 1 transcripts showed an
      eightfold increase of promoter activity over baseline. These data show for the
      first time that human B cells use only one TSS for CB(2) while mouse B cells use
      multiple TSSs and that the mouse TSSs are in a genomic area with promoter
      activity, thus suggesting the location of the gene promoter region. Defining
      these TSSs also provides clues to the various gene regulatory factors involved in
      the expression of CB(2) during B cell activation.

PMID- 19757079
TI  - Nanocarrier for the transdermal delivery of an antiparkinsonian drug.
AB  - The purpose of the present study was to investigate the potential of
      nanoemulsions as nanodrug carrier systems for the percutaneous delivery of
      ropinirole. Nanoemulsions comprised Capryol 90 as the oil phase, Tween 20 as the
      surfactant, Carbitol as the cosurfactant, and water as an external phase. The
      effects of composition of nanoemulsion, including the ratio of surfactant and
      cosurfactant (Smix) and their concentration on skin permeation, were evaluated.
      All the prepared nanoemulsions showed a significant increase in permeation
      parameters such as steady state flux (Jss) and permeability coefficient (Kp) when
      compared to the control (p<0.01). Nanoemulsion composition (NEL3) comprising
      ropinirole (0.5% w/w), Capryol 90 (5% w/w), Smix 2:1 (35% w/w), and water (59.5%
      w/w) showed the highest flux (51.81+/-5.03 microg/cm2/h) and was selected for
      formulation into nanoemulsion gel. The gel was further optimized with respect to
      oil concentration (Capryol 90), polymer concentration (Carbopol), and drug
      content by employing the Box-Behnken design, which statistically evaluated the
      effects of these components on ropinirole permeation. Oil and polymer
      concentrations were found to have a negative influence on permeation, while the
      drug content had a positive effect. Nanoemulsion gel showed a 7.5-fold increase
      in skin permeation rate when compared to the conventional hydrogel. In
      conclusion, the results of the present investigation suggested a promising role
      of nanoemulsions in enhancing the transdermal permeation of ropinirole.

PMID- 19757080
TI  - Development and evaluation of buccal bioadhesive tablet of an anti-emetic agent
      ondansetron.
AB  - The aim of the present study was to develop and evaluate a buccal adhesive tablet
      containing ondansetron hydrochloride (OH). Special punches and dies were
      fabricated and used while preparing buccal adhesive tablets. The tablets were
      prepared using carbopol (CP 934), sodium alginate, sodium carboxymethylcellulose
      low viscosity (SCMC LV), and hydroxypropylmethylcellulose (HPMC 15cps) as
      mucoadhsive polymers to impart mucoadhesion and ethyl cellulose to act as an
      impermeable backing layer. The formulations were prepared by direct compression
      and characterized by different parameters such as weight uniformity, content
      uniformity, thickness, hardness, swelling index, in vitro drug release studies,
      mucoadhesive strength, and ex vivo permeation study. As compared with the
      optimized formulation composed of OH--5 mg, CP 934--30 mg, SCMC LV--165 mg, PEG
      6000--40 mg, lactose--5 mg, magnesium stearate--1.5 mg, and aspartame--2 mg,
      which gave the maximum release (88.15%), non-bitter (OH) that form namely
      ondansetron base and complexed ondansetron was used in order to make the selected
      formulation acceptable to human. The result of the in vitro release studies and
      permeation studies through bovine buccal mucosa revealed that complexed
      ondansetron gave the maximum release and permeation. The stability of drug in the
      optimized adhesive tablet was tested for 6 h in natural human saliva; both the
      drug and device were found to be stable in natural human saliva. Thus, buccal
      adhesive tablet of ondansetron could be an alternative route to bypass the
      hepatic first-pass metabolism and to improve the bioavailability of (OH).

PMID- 19757081
TI  - Preparation and evaluation of microemulsion systems containing salicylic acid.
AB  - Microemulsions (MEs) are clear, thermodynamically stable systems. They were used
      to solubilize drugs and to improve topical drug availability. Salicylic acid (SA)
      is a keratolytic agent used in topical products with antimicrobial actions. The
      objective of this work was to prepare and evaluate SA ME systems. Different
      concentrations of SA were incorporated in an ME base composed of isopropyl
      myristate, water, and Tween 80: propylene glycol in the ratio of 15:1. Three ME
      systems were prepared: S2%, S5%, and S10% which contain 2%, 5%, and 10% of SA,
      respectively. Evaluation by examination under cross-polarizing microscope,
      measuring of percent transmittance, pH measurement, determination of the specific
      gravity, assessment of rheological properties, and accelerated stability study
      were carried out. The data showed that the addition of SA markedly affected the
      physical properties of the base. All systems were not affected by accelerated
      stability tests. Stability study for 6 months under ambient conditions was
      carried out for S10%. No remarkable changes were recorded except a decrease in
      the viscosity value after 1 month. The results suggested that ME could be a
      suitable vehicle for topical application of different concentrations of SA.

PMID- 19757082
TI  - Lipidic systems for in vivo siRNA delivery.
AB  - The ability of small-interfering RNA (siRNA) to silence specific target genes not
      only offers a tool to study gene function but also represents a novel approach
      for the treatment of various human diseases. Its clinical use, however, has been
      severely hampered by the lack of delivery of these molecules to target cell
      populations in vivo due to their instability, inefficient cell entry, and poor
      pharmacokinetic profile. Various delivery vectors including liposomes, polymers,
      and nanoparticles have thus been developed in order to circumvent these problems.
      This review presents a comprehensive overview of the barriers and recent progress
      for both local and systemic delivery of therapeutic siRNA using lipidic vectors.
      Different strategies for formulating these siRNA-loaded lipid particles as well
      as the general concern about their safe use in vivo will also be discussed.
      Finally, current advances in the targeted delivery of siRNA and their impacts on
      the field of RNA interference (RNAi)-based therapy will be presented.

PMID- 19757083
TI  - Psychological aspects of cardiovascular disease.

PMID- 19757084
TI  - The construct validity of the illness cognition questionnaire: the robustness of
      the three-factor structure across patients with chronic pain and chronic fatigue.
AB  - BACKGROUND: The Illness Cognition Questionnaire (ICQ; Evers et al., J Consult
      Clin Psychol, 69:1026-1036, 2001) assesses three ways of cognitively evaluating
      the stressful and aversive character of a chronic illness: helplessness,
      acceptance, and perceived benefits. PURPOSE: The purpose of this study was to
      evaluate the construct validity of the ICQ in individuals with chronic pain and
      patients with chronic fatigue. METHOD: The ICQ was administered to 821
      individuals with chronic pain and 295 patients with chronic fatigue. Confirmatory
      factor analyses were performed to assess the hypothesized three-factor structure,
      containing the factors "helplessness," "acceptance," and "perceived benefits." A
      multigroup analysis was performed to investigate the stability of the factor
      structure in both groups. RESULTS: Results confirmed the three-factor structure
      in the two samples. The factor structure was invariant across individuals with
      chronic pain and chronic fatigue. CONCLUSION: As the three-factor structure
      provided a good fit in both groups, we confirm the usefulness of the subscale
      scores in research and clinical practice.

PMID- 19757085
TI  - An anti-inflammatory lectin from Luetzelburgia auriculata seeds inhibits adhesion
      and rolling of leukocytes and modulates histamine and PGE2 action in acute
      inflammation models.
AB  - OBJECTIVES: To study and characterize the in vivo effect of the lectin from
      Luetzelburgia auriculata seed on acute inflammation models. METHODS: The lectin
      was purified from the crude saline extract by affinity chromatography on a guar
      gum matrix. Native, heat-treated, and digested lectin was evaluated for anti
      inflammatory activity by using peritonitis and paw edema models. The anti
      inflammatory activity was characterized by intravital microscopy, nitric oxide
      production, and myeloperoxidase activity. RESULTS: The lectin exhibited anti
      inflammatory activity (2 mg/kg) on both models, reducing local myeloperoxidase
      activity. Galactose or heat treatment (100 degrees C, 10 min) reduced anti
      inflammatory action. Anti-inflammation involves the inhibition of adhesion and
      rolling of leukocytes along with augmentation of nitric oxide in serum. The
      lectin inhibited the edematogenic effect of histamine and prostaglandins (PGE2)
      but did not alter the chemoattractant effect of IL-8. CONCLUSIONS: The results
      indicate that this lectin is a potent anti-inflammatory molecule. Its effects
      engage diverse modulatory events.

PMID- 19757086
TI  - Interleukin-23 receptor gene variants in Hungarian systemic lupus erythematosus
      patients.
AB  - OBJECTIVE: We investigated the association between systemic lupus erythematosus
      (SLE) and polymorphisms of interleukin-23 receptor (IL23R) gene, which was
      recently found to be associated with autoimmune diseases, including Crohn's
      disease, rheumatoid arthritis, psoriasis and ankylosing spondylitis. SUBJECTS: We
      analysed 383 SLE patients and 253 controls for rs11805303, rs10889677, rs1004819,
      rs2201841, rs11209032, 11209026, rs10489629, rs7517847 and rs7530511 variants.
      METHODS: The analysis was carried out using PCR-RFLP methods. Logistic regression
      analysis was used to compare the genotype distributions of the polymorphisms and
      haplotypes between the SLE patients and healthy controls. RESULTS: We observed no
      significant difference of the examined variants between the patient and control
      groups. CONCLUSIONS: Our results suggest that neither single nucleotide variants
      nor haplotypes of IL23R indicate susceptibility to developing SLE in the
      Hungarian population.

PMID- 19757087
TI  - The role of the prostatic stroma in chronic prostatitis/chronic  pelvic pain
      syndrome.
AB  - OBJECTIVE: To confirm the hypothesis of prostatic stromal involvement in chronic
      prostatitis/chronic pelvic pain syndrome (CP/CPPS). MATERIALS AND METHODS: A
      literature review to analyze mechanisms commonly indicated as a cause of CP/CPPS
      that can interfere with the processes of cell growth of smooth muscle fibrocells
      and may cause smooth muscle cell hypertrophy, periurethral edema, and
      inflammation. RESULTS: Our review strongly suggests a prevalent stromal
      involvement, specifically of the smooth muscle cells, in CP/CPPS physiopathology.
      The involvement of the endocrine system, in particular the role of estrogens, the
      neurological pathway mediated by noradrenalin, and the presence of inflammation,
      support the hypothesis that CP/CPPS could be a disease with a prevalent role of
      smooth muscle stromal cells rather than glandular structures. Neurogenous
      inflammation, oxidative stress and psychological factors may be involved in the
      chronic nature of the disease. CONCLUSIONS: We believe that new studies regarding
      chronic prostatitis should also be focused on prostatic stromal involvement in
      the inflammatory pathway.

PMID- 19757088
TI  - Anti-fibrotic effect of thalidomide through inhibiting TGF-beta-induced ERK1/2
      pathways in bleomycin-induced lung fibrosis in mice.
AB  - OBJECTIVES: This study is designed to confirm the anti-fibrotic effect of
      thalidomide on bleomycin-induced lung fibrosis in a mouse model and to identify
      whether this anti-fibrotic effect is associated with inhibition of the
      transforming growth factor-beta (TGF-beta)-induced extracellular signal-regulated
      kinase1/2 (ERK1/2). METHODS AND MATERIALS: C57BL/6 female mice were administered
      blomycin sulfate. In cultured human lung fibroblasts, expressions of type I
      collagen, fibronectin, and either TGF-beta or IL-6 were measured after
      thalidomide treatment by reverse transcription-polymerase chain reaction (RT
      PCR). Expressions of ERK1/2, type I collagen, fibronectin, and TGF-beta1 from
      lung tissues of blomycin-induced mice and from mouse lung fibroblasts were
      evaluated using RT-PCR and western blotting. RESULTS: Thalidomide administration
      significantly inhibits TGF-beta1 mRNA expression in a dose-dependant manner
      following administration of IL-6 and IL-6R. In the analysis of BAL fluids, total
      BAL inflammatory cell counts, TGF-beta1, and IL-6 levels in thalidomide-treated
      mice were significantly reduced when compared with bleomycin-treated mice (p <
      0.01, p < 0.01, and p < 0.001, respectively). Thalidomide inhibited total ERK1/2
      and phospho-ERK1/2 expression after TGF-beta1 stimulation in the RT-PCR and
      western blotting. CONCLUSION: The results of our study suggest that the anti
      fibrotic effect of thalidomide on lung fibrosis may be related to suppression of
      the TGF-beta1-induced ERK1/2 signaling pathway.

PMID- 19757089
TI  - Involvement of constitutive nitric oxide synthase in ghrelin-induced cytosolic
      phospholipase A(2) activation in gastric mucosal cell protection against ethanol
      cytotoxicity.
AB  - Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor, is an
      important regulator of nitric oxide synthase (NOS) and cyclooxygenase (COX)
      enzyme systems, the products of which are of major significance to the processes
      of gastric mucosal defense and repair. Here, using primary culture of rat gastric
      mucosal cells, we report on the mechanism of ghrelin protection against ethanol
      cytotoxicity. We show that the protective effect of ghrelin was associated with
      the increase in NO and PGE2 production, and characterized by a marked up
      regulation in cytosolic phospholipase A(2) (cPLA(2)) activity and arachidonic
      acid (AA) release. The loss in countering effect of ghrelin on the ethanol
      cytotoxicity was attained with constitutive NOS (cNOS) inhibitor, L-NAME, as well
      as indomethacin and a specific COX-1 inhibitor, SC-560, while specific COX-2
      inhibitor, NS-398, and a selective inducible NOS (iNOS) inhibitor, 1400W, had no
      effect. The effect of L-NAME was reflected in the inhibition of ghrelin-induced
      mucosal cell capacity for NO production, cPLA(2) activation, and PGE2 generation,
      whereas indomethacin caused only the inhibition in PGE2 generation. Moreover, the
      ghrelin-induced up-regulation in AA release was reflected in the cPLA(2) enzyme
      protein phosphorylation and S-nitrosylation. Preincubation with L-NAME resulted
      in the inhibition of the ghrelin-induced S-nitrosylation, whereas the ERK
      inhibitor, PD98059, caused the blockage in cPLA(2) protein phosphorylation as
      well as S-nitrosylation. The findings demonstrate that ghrelin protection of
      gastric mucosa against ethanol cytotoxicity involves cNOS-derived NO induction of
      cPLA(2) activation for the increase in PGE2 synthesis. This activation process
      apparently includes the cPLA(2) phosphorylation followed by S-nitrosylation.

PMID- 19757090
TI  - Conformational analysis of thioglycoside derivatives of histo-blood group ABH
      antigens using an ab initio-derived reparameterization of MM4: implications for
      design of non-hydrolysable mimetics.
AB  - Histo-blood group ABH antigens serve as recognition sites for infectious
      microorganisms and tissue lectins in intercellular communication, e.g. in tumor
      progression. Thus, they are of interest as a starting point for drug design. In
      this respect, potent non-hydrolysable derivatives such as thioglycosides are of
      special interest. As prerequisite to enable estimations of ligand properties
      relative to their natural counterparts, conformational properties of the
      thioglycosidic derivatives of ABH trisaccharides and their disaccharide units
      were calculated using systematic and filtered systematic searches with the MM4
      force field. Parameters for the glycosidic torsions of thioglycosides were
      independently derived from ab initio calculations. The resulting energy
      deviations required a reparameterization of MM4 to a new parameter set called
      MM4R. The data sets obtained using MM4R reveal that the thioglycosides have
      somewhat increased levels of flexibility about the major low-energy conformations
      shared with the corresponding O-glycosides. In the trisaccharides, the
      thiosubstitution of the Gal[NAc]alpha1-3Gal linkage leads to a preference for a
      conformation which is the secondary minimum of the natural counterparts. This
      conformation also generates contacts between the N-acetyl group and the fucose
      moiety in the blood group A derivative. Calculations further indicate that
      thiosubstitution of only the Fucalpha1-2Gal linkage does not affect the
      conformational preferences compared to the natural trisaccharide.
      Thiosubstitution of both linkages in the trisaccharide results in increased
      flexibility but the favored conformation of the natural trisaccharides is
      preferred. The study suggests that thioglycoside derivatives of ABH antigens
      could have pharmaceutical interest as ligands of lectins and other carbohydrate
      binding proteins.

PMID- 19757092
TI  - Resolving the vexing question of credentialing: finding the Aristotelian mean.

PMID- 19757091
TI  - Homology modelling of the human adenosine A2B receptor based on X-ray structures
      of bovine rhodopsin, the beta2-adrenergic receptor and the human adenosine A2A
      receptor.
AB  - A three-dimensional model of the human adenosine A2B receptor was generated by
      means of homology modelling, using the crystal structures of bovine rhodopsin,
      the beta2-adrenergic receptor, and the human adenosine A2A receptor as templates.
      In order to compare the three resulting models, the binding modes of the
      adenosine A2B receptor antagonists theophylline, ZM241385, MRS1706, and PSB601
      were investigated. The A2A-based model was much better able to stabilize the
      ligands in the binding site than the other models reflecting the high degree of
      similarity between A2A and A2B receptors: while the A2B receptor shares about 21%
      of the residues with rhodopsin, and 31% with the beta2-adrenergic receptor, it is
      56% identical to the adenosine A2A receptor. The A2A-based model was used for
      further studies. The model included the transmembrane domains, the extracellular
      and the intracellular hydrophilic loops as well as the terminal domains. In order
      to validate the usefulness of this model, a docking analysis of several selective
      and nonselective agonists and antagonists was carried out including a study of
      binding affinities and selectivities of these ligands with respect to the
      adenosine A2A and A2B receptors. A common binding site is proposed for
      antagonists and agonists based on homology modelling combined with site-directed
      mutagenesis and a comparison between experimental and calculated affinity data.
      The new, validated A2B receptor model may serve as a basis for developing more
      potent and selective drugs.

PMID- 19757093
TI  - Cadmium effects on p38/MAPK isoforms in MDA-MB231 breast cancer cells.
AB  - Emerging evidence seems to indicate that the heavy metal cadmium (Cd) is able to
      regulate gene expression, drastically affecting the pattern of transcriptional
      activity in normal and pathological eukaryotic cells, also affecting
      intracellular signalization events. Human p38 is a family of mitogen-activated
      protein kinases consisting of four isoforms (alpha, beta, gamma and delta) which
      mediate signal transduction cascades controlling several aspects of cell
      physiology. In this study we examined whether exposure of MDA-MB231 tumor cells
      from the human breast to Cd may exert some effect on p38 isoform expression and
      accumulation, as well as on p38 activation. Employing a combination of
      proliferation tests, conventional and semiquantitative multiplex (SM)-polymerase
      chain reaction (PCR) and Western blot assays, we report that the treatment of
      breast cancer cells with 5 microM CdCl(2) induces a diversified modulation of the
      transcription patterns of p38 isoform genes and of the accumulation of the
      related protein products, which are, on the other hand, also affected by alpha
      and beta isoform functional inactivation induced by SB203580. Our findings
      suggest the existence of so far unexplored mechanisms of gene regulation in our
      model system and validate that MDA-MB231 cell line is a suitable in vitro model
      for further and more detailed studies on the intracellular mechanisms underlying
      the control of p38 expression, synthesis and activation in mammary tumor cells
      exposed to different stresses.

PMID- 19757094
TI  - A novel 4-hydroxycoumarin biosynthetic pathway.
AB  - Coumarin forms in melilotoside (trans-ortho-coumaric acid glucoside)-containing
      plant species upon cell damage. In moldy melilotoside-containing plant material,
      trans-ortho-coumaric acid is converted by fungi to 4-hydroxycoumarin, two
      molecules of which spontaneously combine with formaldehyde to give dicoumarol.
      Dicoumarol causes internal bleeding in livestock and is the forerunner of the
      warfarin group of medicinal anticoagulants. Here, we report 4-hydroxycoumarin
      formation by biphenyl synthase (BIS). Two new BIS cDNAs were isolated from
      elicitor-treated Sorbus aucuparia cell cultures. The encoded isoenzymes preferred
      ortho-hydroxybenzoyl (salicoyl)-CoA as a starter substrate and catalyzed a single
      decarboxylative condensation with malonyl-CoA to give 4-hydroxycoumarin. When
      elicitor-treated S. aucuparia cell cultures were fed with the N-acetylcysteamine
      thioester of salicylic acid, 4-hydroxycoumarin accumulated in the culture medium.
      Incubation of the BIS isoenzymes with benzoyl-CoA and malonyl-CoA resulted in the
      formation of 3,5-dihydroxybiphenyl which is the precursor of the phytoalexins of
      the Maloideae.

PMID- 19757095
TI  - Role of ENA ATPase in Na(+) efflux at high pH in bryophytes.
AB  - Potassium or Na(+) efflux ATPases, ENA ATPases, are present in all fungi and play
      a central role in Na(+) efflux and Na(+) tolerance. Flowering plants lack ENA
      ATPases but two ENA ATPases have been identified in the moss Physcomitrella
      patens, PpENA1 and PpENA2. PpENA1 mediates Na(+) efflux in Saccharomyces
      cerevisiae. To propose a general function of ENA ATPases in bryophytes it was
      necessary to demonstrate that these ATPases mediate Na(+) efflux in planta and
      that they exist in more bryophytes than P. patens. For these demonstrations (1)
      we cloned a third ATPase from P. patens, PpENA3, and studied the expression
      pattern of the three PpENA genes; (2) we constructed and studied the single and
      double Deltappena1 and Deltappena2 mutants; and (3) we cloned two ENA ATPases
      from the liverwort Marchantia polymorpha, MpENA1 and MpENA2, and expressed them
      in S. cerevisiae. The results from the first two approaches revealed that the
      expression of ENA ATPases was greatly enhanced at high pH and that Na(+) efflux
      at high pH depended on PpENA1. The ENA1 ATPase of M. polymorpha suppressed the
      defective growth of a S. cerevisiae mutant at high K(+) or Na(+) concentrations,
      especially at high K(+).

PMID- 19757096
TI  - Amplification of repetitive DNA and origin of a rare chromosomal sex bivalent in
      Deltochilum (Calhyboma) verruciferum (Coleoptera, Scarabaeidae).
AB  - The most intriguing karyotypic variation in the Coleoptera involves variation in
      sex chromosome structure, origin and behavior. In this report we describe
      chromosomal characteristics of Deltochilum (Calhyboma) verruciferum (Coleoptera,
      Scarabaeidae) using conventional and differential cytogenetic techniques, with
      emphasis on the description of a rare sex bivalent in the Coleoptera and
      dispersion of repetitive DNA. This species shows 2n = 20,XY(p) with biarmed
      chromosomes. Analysis of constitutive heterochromatin through C-banding revealed
      mainly diphasic autosomes with short heterochromatic arms, while the X was
      completely heterochromatic and the Y was heterochromatic in the long arm. This
      pattern was confirmed through the use of CMA(3) fluorochrome that stained all
      heterochromatic regions. Silver nitrate staining marked all heterochromatic
      regions and the lumen of the sex bivalent in metaphase I. These results indicated
      that karyotypic differentiation in D. (C.) verruciferum involved autosomal
      amplification and dispersion of repetitive DNA and the origin of unusual sex
      chromosomes (XY(p)), generating a unique karyotype in this species.

PMID- 19757097
TI  - Transposition of fly mariner elements into bacteria as a genetic tool for
      mutagenesis.
AB  - Mariner eukaryotic elements transpose randomly and independently of any host
      factors, making them ideal tools for random mutagenesis in bacteria, including
      genetically intractable microorganisms. The transposable element Himar1, a member
      of the mariner family of transposons, originally isolated from the horn fly
      (Haematobia irritans), has thus been extensively used to generate large numbers
      of insertion mutants. Transposon-based approaches greatly facilitate studies of
      bacterial biology. We summarize the current mariner-based transposon tools and
      techniques for conducting genetic studies in bacteria.

PMID- 19757098
TI  - Genital feelers: the putative role of parameres and aedeagal  sensilla in
      Coleoptera Phytophaga (Insecta).
AB  - The male copulatory organ (aedeagus) of the Curculionoidea and the Chrysomeloidea
      is originally composed of a median lobe and a tegmen with basal struts and distal
      parameres. Within the Phytophaga (=Pseudotetramera), the parameres have been
      reduced several times. Comparison of different types of parameres, median lobes,
      aedeagi lacking parameres, and investigation of dissected pairs in copula
      revealed that (1) parameres do not provide mechanical coupling, (2) mechanical
      footing is provided by the endophallus, (3) median lobes of Phytophaga bear
      different kinds of sensilla. Mechanical and behavioural interaction between male
      and female copulatory organs were studied morphologically and by observation of
      live, copulating pairs. For the first time, copulation of a Sagrinae-species
      (Chrysomelidae: Sagrinae: Mecynodera coxalgica) was investigated in detail.

PMID- 19757099
TI  - Life cycle and behaviour of the predaceous mite  Cunaxatricha tarsospinosa
      (Acari: Prostigmata:  Cunaxidae).
AB  - Life cycle and behaviour of Cunaxatricha tarsospinosa Castro & Den Heyer from
      rubber trees in Brazil were studied, with Tenuipalpus heveae Baker offered as
      prey.The study was conducted at 25.4 +/- 0.2 degree C, 83 +/- 5% RH and 12:12 h
      L:D photophase. The egg stage was the longest immature stage, lasting 17.1 +/-
      1.3 days (mean +/- SE); total juvenile development was completed in 33.2 +/- 2.8
      days. Lifetime fecundity was 12.0 +/- 2.2 eggs. Intrinsic rate of population
      increase was low, suggesting that T. heveae may not be a good prey for the
      predator. All specimens of C. tarsospinosa collected in the Weld for this study
      were females, no males were found. Concurrently, only females were obtained in
      the laboratory. This seems to be the first report of thelytokous parthenogenesis
      for cunaxids.Similar to earlier reports for some Cunaxinae and Coleoscirinae,
      prey were captured when predators were actively searching for them.

PMID- 19757100
TI  - The impact of eriophyoids on crops: recent issues on Aculus schlechtendali,
      Calepitrimerus vitis and Aculops lycopersici.
AB  - The nature of the damage caused by eriophyoid mites and the assessment of yield
      losses still require detailed studies if appropriate control and risk mitigation
      strategies are to be planned. The economic importance of eriophyoid mites is
      increasing worldwide and a lot of species have reached a permanent pest status in
      certain crops, while others represent a quarantine threat for several countries.
      Due to their relevant role in Europe and elsewhere, three eriophyoid mites that
      have been frequently reported in recent research, are here considered as case
      studies: two of them (the apple rust mite, Aculus schlechtendali, and the grape
      rust mite, Calepitrimerus vitis) colonise temperate fruits, while one (the tomato
      russet mite, Aculops lycopersici) affects vegetables. The damage assessment
      related to the apple rust mite has been evaluated on different apple varieties
      with implications for pest control. Some factors affecting the spread and
      economic importance of the grape rust mite have been identified. The complexity
      and difficulty in controlling the tomato russet mite by chemicals enhances the
      interest in biological control agents. Considerations on interactions between
      eriophyoids and host plants (e.g. resistance, varietal susceptibility), on pest
      management regimes (e.g. impact of fungicides, resistance to acaricides,
      perspectives on biological control) are presented.

PMID- 19757101
TI  - An orthopedic injection training instrument using flow impedance to indicate
      needle tip locations.
AB  - OBJECTIVE: The project aimed to design an instrument that can provide visual,
      quantitative feedback to medical students and help them develop intuitive,
      tactile-based injection skills. METHODS: The instrument uses force and
      displacement sensors to find flow impedance, the ratio of the pressure applied to
      fluid in the syringe to the fluid flow rate, of different tissues. A software
      program utilizes these flow impedances to identify needle tip location-either
      joint or tendon. Injection experiments with pork feet were completed to collect
      flow impedance data when the needle tip was located in joint or tendon.
      Injections used deionized water and aqueous pullulan solutions to study the
      instrument's effectiveness when medical therapies of different viscosities are
      injected. For each solution, at least 13 injections were conducted. The mean and
      standard deviation of the flow impedances from injections with each solution were
      obtained. RESULTS: In all experimental cases, the flow impedance demonstrated by
      the tendon is a number of times higher than that of the joint cavity: the
      impedance ratios (tendon to joint cavity) for water, 3 w/w% pullulan, and 15 w/w%
      pullulan are 74, 62, and 6, respectively. CONCLUSIONS: The results confirmed the
      concept of using flow impedance to index the needle tip location-whether the tip
      is positioned in joint or tendon. This instrument's user interface can serve as a
      training aid for medical students and infrequent operators.

PMID- 19757102
TI  - Guidelines for intraoperative neuromonitoring using raw (analog or digital
      waveforms) and quantitative electroencephalography: a position statement by the
      American Society of Neurophysiological Monitoring.
AB  - BACKGROUND CONTEXT: Electroencephalography (EEG) is one of the oldest and most
      commonly utilized modalities for intraoperative neuromonitoring. Historically,
      interest in the EEG patterns associated with anesthesia is as old as the
      discovery of the EEG itself. The evolution of its intraoperative use was also
      expanded to include monitoring for assessing cortical perfusion and oxygenation
      during a variety of vascular, cardiac, and neurosurgical procedures. Furthermore,
      a number of quantitative or computer-processed algorithms have also been
      developed to aid in its visual representation and interpretation. The primary
      clinical outcomes for which modern EEG technology has made significant
      intraoperative contributions include: (1) recognizing and/or preventing
      perioperative ischemic insults, and (2) monitoring of brain function for
      anesthetic drug administration in order to determine depth of anesthesia (and
      level of consciousness), including the tailoring of drug levels to achieve a
      predefined neural effect (e.g., burst suppression). While the accelerated
      development of microprocessor technologies has fostered an extraordinarily rapid
      growth in the use of intraoperative EEG, there is still no universal adoption of
      a monitoring technique(s) or of criteria for its neural end-point(s) by
      anesthesiologists, surgeons, neurologists, and neurophysiologists. One of the
      most important limitations to routine intraoperative use of EEG may be the lack
      of standardization of methods, alarm criteria, and recommendations related to its
      application. Lastly, refinements in technology and signal processing can be
      expected to advance the usefulness of the intraoperative EEG for both anesthetic
      and surgical management of patients. OBJECTIVE: This paper is the position
      statement of the American Society of Neurophysiological Monitoring. It is the
      practice guidelines for the intraoperative use of raw (analog and digital) and
      quantitative EEG. METHODS: The following recommendations are based on trends in
      the current scientific and clinical literature and meetings, guidelines published
      by other organizations, expert opinion, and public review by the members of the
      American Society of Neurophysiological Monitoring. This document may not include
      all possible methodologies and interpretative criteria, nor do the authors and
      their sponsor intentionally exclude any new alternatives. RESULTS: The use of the
      techniques reviewed in these guidelines may reduce perioperative neurological
      morbidity and mortality. CONCLUSIONS: This position paper summarizes commonly
      used protocols for recording and interpreting the intraoperative use of EEG.
      Furthermore, the American Society of Neurophysiological Monitoring recognizes
      this as primarily an educational service.

PMID- 19757103
TI  - Prooxidative effects of green tea polyphenol (-)-epigallocatechin-3-gallate on
      the HIT-T15 pancreatic beta cell line.
AB  - Epigallocatechin-3-gallate (EGCG) is the main polyphenolic constituent in green
      tea and is believed to function as an antioxidant. However, increasing evidence
      indicates that EGCG produces reactive oxygen species (ROS) and subsequent cell
      death. In this study, we investigated the prooxidative effects of EGCG on the HIT
      T15 pancreatic beta cell line. Dose-dependent cell viability was monitored with
      the cell counting kit-8 assay, while the induction of apoptosis was analyzed by a
      cell death ELISA kit and comet assay. Extracellular H(2)O(2) was determined using
      the Amplex Red Hydrogen Peroxide Assay Kit. Intracellular oxidative stress was
      measured by fluorometric analysis of 2',7'-dichlorofluorescin (DCFH) oxidation
      using DCFH diacetate (DA) as the probe. Treatment with EGCG (5-100 microM)
      decreased the viability of pancreatic beta cells, caused concomitant increases in
      apoptotic cell death, and increased the production of H(2)O(2) and ROS. Catalase,
      the iron-chelating agent diethylenetriaminepentaacetic acid, and the Fe(II)
      specific chelator o-phenanthroline all suppressed the effects of EGCG, indicating
      the involvement of both H(2)O(2) and Fe(II) in the mechanism of action of EGCG.
      The antioxidant N-acetyl-cysteine and alpha-lipoic acid also suppressed the
      effects of EGCG. Furthermore, EGCG did not scavenge exogenous H(2)O(2), but
      rather, it synergistically increased H(2)O(2)-induced oxidative cell damage in
      pancreatic beta cells. Together, these findings suggest that in the HIT-T15
      pancreatic beta cell line, EGCG mediated the generation of H(2)O(2), triggering
      Fe(II)-dependent formation of a highly toxic radical that in turn induced
      oxidative cell damage.

PMID- 19757104
TI  - Diverse actions of ouabain and its aglycone ouabagenin in renal cells.
AB  - The cellular actions of ouabain are complex and involve different pathways,
      depending on the cell type and experimental conditions. Several studies have
      reported that Madin-Darby canine kidney (MDCK) cellular sensitivity to ouabain is
      not related to Na-K-ATPase inhibition, and others showed that some cell types,
      such as Ma104, are resistant to ouabain toxicity albeit their Na-K-ATPase
      isoforms possess high affinity for this glycoside. We describe here that the
      effects of ouabain and ouabagenin also diverge in MDCK and Ma104 cells, being
      MDCK cells more resistant to ouabagenin, while Ma104 cells are resistant to both
      molecules. This feature seems to correlate with induction of cell signaling,
      since ouabain, but not ouabagenin, induced an intense and sustained increase in
      tyrosine phosphorylation levels in MDCK cells. Moreover, ouabain-induced
      phosphorylation in Ma104 cells was approximately half than that observed in MDCK
      cells. The proportion between alpha and beta subunits of Na-K-ATPase was similar
      in MDCK cells, though Ma104 cells presented more alpha subunits, located mainly
      at the cytoplasm. Furthermore, a fluorescent ouabain-analog labeled mainly the
      cytoplasm of Ma104 cells, the opposite of that seen in MDCK cells, corroborating
      the results using anti-Na-K-ATPase antibodies. Hence, the results suggest that
      ouabain and ouabagenin differ in terms of Na-K-ATPase inhibition and cell
      signaling activation in MDCK cells. Additionally, MDCK and Ma104 cell lines
      respond differently to ouabain, perhaps due to an intrinsic ability of this
      glycoside to selectively reach the cytoplasm of Ma104 cells.

PMID- 19757105
TI  - Unstable transmission of rice chromosomes without functional centromeric repeats
      in asexual propagation.
AB  - During sexual propagation of primary trisomic 8, chromosome 8 breaks in some rice
      plants, resulting in a telotrisomic (2n+.8S) line. In this study, we observed
      that the extra short arm of chromosome 8 (.8S) can easily be lost in the
      telotrisomic, and we determined by fluorescence in-situ hybridization (FISH)
      analysis that the centromeric region of the extra .8S did not contain the rice
      centromeric satellite repeat (CentO) and centromere-specific retrotransposon
      (CRR); however, the extra .8S contained part of the CentO and CRR sequences in
      the initially preserved telotrisomic line. We confirmed by real-time quantitative
      PCR (RQ-PCR) analysis that the original functional centromere of the extra .8S
      was lost. Using both FISH and RQ-PCR, the breakage point of the extra .8S was
      found within the BAC clone a0070J19 sequence containing the first part of the
      short arm near the centromere region of chromosome 8 but without any CentO or CRR
      sequences. However, part of the DNA sequence within the a0070J19 BAC clone played
      a role in the new functional centromere, contributing to the morphological
      variations by asexually propagated plants of rice telotrisomics in the field. We
      conclude that CENH3, a key element in the eukaryotic kinetochore, may not always
      bind properly with the new functional centromere, resulting in loss of the extra
      .8S during mitosis and the chromosome numbers returning to diploid levels in
      subsequent generations.

PMID- 19757106
TI  - Computer-aided quantification of retinal neovascularization.
AB  - Rodent models of retinal angiogenesis play a pivotal role in angiogenesis
      research. These models are a window to developmental angiogenesis, to
      pathological retinopathy, and are also in vivo tools for anti-angiogenic drug
      screening in cancer and ophthalmic research. The mouse model of oxygen-induced
      retinopathy (OIR) has emerged as one of the leading in vivo models for these
      purposes. Many of the animal studies that laid the foundation for the recent
      breakthrough of anti-angiogenic treatments into clinical practice were performed
      in the OIR model. However, readouts from the OIR model have been time-consuming
      and can vary depending on user experience. Here, we present a computer-aided
      quantification method that is characterized by (i) significantly improved
      efficiency, (ii) high correlation with the established hand-measurement
      protocols, and (iii) high intra- and inter-individual reproducibility of results.
      This method greatly facilitates quantification of retinal angiogenesis while at
      the same time increasing lab-to-lab reproducibility of one of the most widely
      used in vivo models in angiogenesis research.

PMID- 19757107
TI  - The impact of an industrial complex on freshly deposited sediments, Chener Rahdar
      river case study, Shiraz, Iran.
AB  - Concentrations of elements (As, Co, Cu, Ni, Mo, Pb, V, and Zn) are studied in the
      sediments of two adjacent stretches of Chenar Rahdar river. The first stretch
      (S1) is influenced by urban and arable land wastewater, and the second (S2) is
      mainly loaded with industrial effluents. The average abundance order of heavy
      metals content in S1 sediments is Ni > V > Zn > Cu > Co > As > Pb > Mo and in S2
      sediments is Ni > Zn > V > Cu > Mo > Pb > Co > As. The maximum average
      concentration for these heavy metals (except for As) occurs in the S2 sediments.
      The contamination factor (CF) base of background in S1 for eight analyzed
      elements is moderate. The CF for Cu, Zn, and Pb in S2 sediments is considerable.
      The highest CF in S1 and S2 sediments is observed for Mo (CF = 10.95 and 12.41)
      and indicates very high contamination. The application of modified degree of
      contamination values (mC(d)) indicates low and high degree of contamination (1.89
      4.15) in S1 and S2, respectively. Calculated enrichment factors (EF) reveal
      enrichment of Mo and As in S1 and Zn, Cu, Mo, and Pb in S2 compared to the
      average abundances of background level. The maximum EF for Mo is 7.61
      (significant enrichment), while Pb, Zn, and Cu with maximum EF between 2 and 5
      indicate moderate contamination. Principal component analysis (PCA) shows
      distinctly different elemental associations in S1 and S2 sediments. The strong
      association of Zn, Co, Ni, Sc, Cu, Al and Fe in S1 suggests a similar source. The
      results of PCA for Zn, Pb, Mo and Cu in S2 (componente2) indicate that these
      metals are influenced by anthropogenic activity. Also, high loading heavy metals
      with OC (0.97) indicate that organic carbon plays a significant role in the
      distribution and sorption of these heavy metals in the sediments. Factor analysis
      indicates that As and Mo behave differently in sediment samples.

PMID- 19757108
TI  - Temporal variation in density and diversity of cyanobacteria and cyanotoxins in
      lakes at Nagpur (Maharashtra State), India.
AB  - Toxic cyanobacteria (TCB) are known worldwide for the adverse impacts on humans
      and animals. Species composition and the seasonal variation of TCB in water
      bodies depend on interactions between physical and chemical factors. The present
      investigation delineates temporal variations in physico-chemical water quality
      parameters, viz. nutrients and density, diversity, and distribution of toxic
      cyanobacteria and cyanotoxins in Lake Ambazari (21 degrees 7'52''N, 79 degrees
      2'22''E) and Lake Phutala (21 degrees 9'18''N, 79 degrees 2'37''E) at Nagpur
      (Maharashtra State), India. These lakes are important sources of recreational
      activities and fisheries. Toxic cyanobacterial diversity comprised Anabaena,
      Oscillatoria, Lyngbya, Phormidium, and Microcystis, a well-known toxic
      cyanobacterial genus, as dominant. Chlorophyll-a concentrations in the lakes
      ranged from 1.44 to 71.74 mg/m(3). A positive correlation of Microcystis biomass
      existed with orthophosphate-P (p < 0.05) and nitrate-N (p > 0.05). Identification
      and quantification of microcystin variants were carried out by high performance
      liquid chromatography equipped with photodiode array detector. Among all the
      tested toxin variants, microcystin-RR (arginine-arginine) was consistently
      recorded and exhibited a positive correlation (p < 0.05) with Microcystis in both
      the water bodies. Microcystis bloom formation was remarkable between post-monsoon
      and summer. Besides nutrient concentrations governing bloom formation, the
      allelopathic role of microcystins needs to be established.

PMID- 19757109
TI  - Pesticide residues in soils, sediments, and vegetables in the Red River Delta,
      northern Vietnam.
AB  - This study assessed pesticide residues in soils, sediments, and vegetables in the
      Xuan Khe and Hop Ly communes located along the Chau Giang River in the Red River
      Delta, northern Vietnam. Samples were collected from agricultural areas within
      and outside of embankments built to prevent flooding. In Xuan Khe, the soils
      outside of the embankment were more clayey with higher organic matter contents
      compared with the inside, due to selective deposition during river flooding. Many
      of the soils contained significant amounts of pesticides including
      dichlorodiphenyltrichloroethane (DDT), dicofol, isoprothiolane, and metalaxyl
      although their levels were below the maximum allowable concentration set by the
      Vietnamese government. The spectrum of DDT derivatives found suggested that the
      source of DDTs was not contaminated dicofol. Soils in Hop Ly resembled soils in
      Xuan Khe but were relatively sandy; one field showed appreciable contents of DDT
      derivatives. The ratios of (p,p(')-dichlorodiphenyldichloroethylene + p,p(')
      dichlorodiphenyldichloroethane)/ summation operatorDDT in the surface and
      subsurface soils in Hop Ly were 0.34 and 0.57, suggesting that the DDTs
      originated from recent application. Pesticide residues in soils were not likely
      to translocate into vegetable crops, except for metalaxyl. High concentrations of
      cypermethrins in kohlrabi leaves could be ascribed to foliar deposition.

PMID- 19757110
TI  - Experimental investigation of cesium mobility in the course of secondary mineral
      formations in Hanford sediment columns at 50 degrees C.
AB  - Formation of secondary minerals and Cs mobility in Hanford sediments were
      investigated under conditions similar to the Hanford tank leak in a dynamic flow
      system at 50 degrees C. The objectives were to (1) examine the nature and
      locations of secondary mineral phases precipitated in the sediments and (2)
      quantify the amount of Cs retained by the sediment matrix at 50 degrees C. To
      this end, Hanford sediments were packed into 10-cm long columns and leached with
      simulated tank waste consisting of 1.4 M NaOH, 0.125 M NaAlO(2), 3.7 M NaNO(3),
      and 1.3 x 10(-4) M Cs at 50 degrees C. Compositions of outflow solution were
      monitored with time for up to 25 days, and the columns were then segmented into
      four 2.5-cm long layers. The colloidal fraction in these segments was
      characterized in terms of mineralogy, particle morphology, Cs content, and short
      range Al and Si structure. It was observed that cancrinite and sodalite
      precipitated at 50 degrees C. Approximately 53% Cs was retained in the column
      treated by the simulated tank waste at this temperature. Cesium retention in the
      column was lowered in the high ionic strength solution due to competition from Na
      for the exchange sites. This can be explained by alteration of distribution and
      number of sorption sites which reduces the selectivity of Cs for Na, and through
      the formation of cancrinite and sodalite. The formation of hydroxide complexes in
      highly alkaline solutions could also contribute to relatively poor retention of
      Cs by hindering ion exchange mechanism.

PMID- 19757111
TI  - Factors regulating trophic status in a large subtropical reservoir, China.
AB  - We evaluated a 4-year data set (July 2003 to June 2007) to assess the trophic
      state and its limiting factors of Three-Gorges Reservoir (TGR), China, a large
      subtropical reservoir. Based on Carlson-type trophic state index (TSI)(CHL), the
      trophic state of the system was oligotrophic (TSI(S) < 40) in most months after
      the reservoir became operational, although both TSI(TP) and TSI(TN) were higher
      than the critical value of eutrophic state (TSI(S) > 50). Using Carlson's (1991)
      two-dimensional approach, deviations of the TSI(S) indicated that factors other
      than phosphorus and nitrogen limited algal growth and that nonalgal particles
      affected light attenuation. These findings were further supported by the
      significant correlation among the values of TSI(CHL) - TSI(SD) and nonvolatile
      suspended solids and water residence time. The logarithmic model showed that an
      equivalent TSI(CHL) and TSI(SD) could be found at tau = 54 days in the TGR (Fig.
      7). Accordingly, nonalgal particulates dominated light attenuation and limited
      algal biomass of the reservoir when tau < 54 days.

PMID- 19757112
TI  - delta-Aminolevulinic acid dehydratase of Haloarcula argentinensis isolated from
      Tuz Lake in Turkey.
AB  - The delta-aminolevulinic acid dehydratase (ALAD) enzyme of a novel record for
      Turkish microbial flora was studied. The isolate I-113 was obtained from Tuz Lake
      in Turkey and identified as Haloarcula argentinensis. The ALAD enzyme of the
      isolate was assayed in order to determine its requirements and to be used as
      biomarker for lead pollution in it's ambient. In enzymic studies, the effects of
      various metals (Cd, Co, Mg, Mn, Ni, Pb, and Zn), pH (3-11), temperatures (25-55
      degrees C), and salinity (15-25%) conditions have been examined. The data
      obtained from the studies were analyzed statistically by using Kruskal-Wallis,
      Mann-Whitney, correlation, regression, variance analysis, and significance tests
      were performed by using SPSS 10.0 for Windows. Although its optimum pH was
      determined as 7, it was still active at pH 3-11. The optimal temperature for the
      enzyme was observed to be 30 degrees C. Mn and Pb inhibited its activity
      significantly (p < 0.05) while Zn increased it slightly. The ALAD enzyme in H.
      argentinensis could be used as a biomarker for Pb contamination.

PMID- 19757113
TI  - Sequential fractionation of phosphorus in sediments of El-Fayum lakes--Egypt.
AB  - The amounts and forms of potentially mobile phosphorus (P) in surface sediments
      of Qarun and Wadi El-Rayan lakes were evaluated during winter and summer using a
      sequential chemical extraction. Five sedimentary P fractions were separately
      quantified: loosely sorbed P (NH(4)Cl-P), iron-associated P (BD-P), calcium-
      bound P (HCl-P), metal oxide bound P (NaOH-P), and residual P (organic and
      refractory P). The results indicated that the fractional composition of the
      examined lakes was different while the total P concentrations were approached.
      The inorganic P in the surface sediment mainly consisted of Ca-P followed by Fe-P
      in Qarun Lake, while Al-P took the second order in Wadi El-Rayan lakes. The ranks
      order of the different P extracts were HCl-P > residual-P approximately NaOH-P >
      NH(4)Cl-P > BD-P and residual-P > NH(4)Cl-P > HCl-P > NaOH-P > BD-P for Qarun and
      Wadi El-Rayan lakes, respectively.

PMID- 19757114
TI  - Seasonal changes in the concentrations of nitrogen and phosphorus in farmland
      drainage and groundwater of the Taihu Lake region of China.
AB  - To reduce the harmful effects of irrigated agriculture on the environment, the
      evaluation of alternative irrigation water management practices is essential. The
      contents of total-phosphorus, nitrate nitrogen, and ammonium nitrogen in rural
      aquatic bodies typical of the Taihu Lake region (Yixing, Wangzhuang, and
      Xinzhuang) were determined during 2 years. The results showed that the
      concentrations of nitrogen and phosphorus during the rainy season were higher
      than in other months. The concentration of ammonium nitrogen in farmland drainage
      was higher than that of nitrate nitrogen. Ammonium nitrogen and nitrate nitrogen
      were the main pollution sources in rural groundwater. However, the pollution by
      ammonium nitrogen was worse than nitrate nitrogen. The annual average values of
      ammonium nitrogen in Yixing and Wangzhuang were 1.596 and 2.103 mg L(-1); with
      maximum values of 5.782 and 5.441 mg L(-1), respectively, exceeding the lower
      limit for type V water quality by a factor of 10. Concentrations of nitrate
      nitrogen in groundwater in Xinzhuang from May to September exceeded the limit
      value (10 mg L(-1)) for drinking water prescribed by the World Health
      Organization. Therefore, this groundwater was not suitable to drink. In Taihu
      Lake, the average concentration of phosphorus over 2 years was 0.492 mg L(-1) and
      pollution by phosphorus in Taihu Lake was worse than other farmland drainage
      because of the trend of total-phosphorus accumulation. In addition, the average
      concentrations of nitrate nitrogen and ammonium nitrogen in Taihu Lake were 2.152
      and 2.885 mg L(-1), respectively over 2 years, indicating that the water in the
      Taihu Lake is constantly in danger of eutrophication. Because of the
      transformation of ammonium nitrogen to nitrate nitrogen, there was a connection
      between the concentrations of ammonium nitrogen in farmland drainage and nitrate
      nitrogen in groundwater. There was also a significant positive linear correlation
      between the concentrations of ammonium nitrogen in farmland drainage and in
      shallow groundwater.

PMID- 19757115
TI  - The changes in different ozone metrics and their implications following precursor
      reductions over northern Taiwan from 1994 to 2007.
AB  - The changes of different O(3) metrics such as O(3_avg) (daily mean), O(X) (NO(2)
      + O(3)), O(3_8h) (daily maximum 8-h moving average), O(3_max) (daily maximum 1-h
      average), and exceedances of O(3_8h) and O(3_max) at 16 air quality monitoring
      stations over northern Taiwan from 1994 to 2007 are evaluated. The O(3_avg) at
      the background site displays an increasing trend at 0.54 +/-0.21 ppb (1.28 +/
      0.49%) per year. The O(X) at urban sites shows a significant increase, indicating
      that even with the effect of reduced NO titration increasing photochemical
      production is evident. The exceedances of O(3_8h) (>80 ppb) are about 14.9%
      higher than O(3_max) (>120 ppb) with more exceedances at coastal or background
      sites, where the anthropogenic O(3) precursor emissions are lower. In addition to
      increasing background O(3) and reductions in NO titration, increasing O(3)
      production efficiency also plays a key role in the increase of moderate to high
      O(3) concentrations. The findings help explain the different trends in
      exceedances and levels of O(3_8h) and O(3_max) and are likewise important in the
      formation of O(3) control strategies.

PMID- 19757116
TI  - Using a hybrid approach to optimize experimental network design for aquifer
      parameter identification.
AB  - This research develops an optimum design model of groundwater network using
      genetic algorithm (GA) and modified Newton approach, based on the experimental
      design conception. The goal of experiment design is to minimize parameter
      uncertainty, represented by the covariance matrix determinant of estimated
      parameters. The design problem is constrained by a specified cost and solved by
      GA and a parameter identification model. The latter estimates optimum parameter
      value and its associated sensitivity matrices. The general problem is simplified
      into two classes of network design problems: an observation network design
      problem and a pumping network design problem. Results explore the relationship
      between the experimental design and the physical processes. The proposed model
      provides an alternative to solve optimization problems for groundwater
      experimental design.

PMID- 19757117
TI  - Field evaluation of an innovative stormwater treatment device--the Stormvault
      system.
AB  - Stormvault is a new volume-control-based underground stormwater treatment system,
      which is well suited for implementation in urban areas. In order to evaluate the
      hydrologic and hydraulic function of the system and assess the pollutant removal
      capacity of the system, a field monitoring program was implemented during both
      wet and dry weather conditions for 2 years. The pollutants of interest were total
      suspended solids (TSS), chemical oxygen demand (COD), total phosphorus (TP), and
      orthophosphate (OP). Data of 35 storms obtained were then analyzed by using
      several methods, such as the efficiency ratios, the summation of loads, and the
      relative achievable efficiency (RAE) methods to obtain estimates for the
      pollutant removal efficiencies of the Stormvault unit. Results show the following
      average efficiencies: TSS 82.46%, COD 73.10%, TP 47.37%, and OP 52.54%.
      Statistical significance and variation of removal efficiency with inlet
      concentration were also examined.

PMID- 19757118
TI  - Occurrence and distribution of polycyclic aromatic carbons in sludges from
      wastewater treatment plants in Guangdong, China.
AB  - In this study, the occurrence and distribution of polycyclic aromatic
      hydrocarbons (PAHs) were investigated in six sludge samples collected from
      Guangdong Province, China. Concentrations of PAHs varying from 2,534.1 to 6,926.6
      microg kg(-1) (dry sludge) were observed in three municipal wastewater treatment
      plants with phenanthrene (Phe), fluoranthene, and pyrene being the main
      compounds. In addition, 682.6 microg kg(-1) PAHs were detected in one sludge
      sample from a food processing plant, with fluorene, Phe, and chrysene being the
      main components. No PAHs were detected in sludge samples obtained from two
      cosmetic plants. The levels and distributional characteristics of PAHs,
      polychlorinated biphenyls (PCBs), and polycyclic musks (PMs) from the samples
      were also compared. The results of this comparison indicated that petrochemical
      refineries and road traffic played important roles in the PAH loads in sludge,
      while PMs primarily originated from domestic wastewater and industrial wastewater
      from cosmetic plants. Finally, the presence of 98.8 microg kg(-1) PCBs in sludge
      suggested diffusional emission sources from electrical components containing
      PCBs.

PMID- 19757119
TI  - Assessment of current status of zinc in wastewater treatment plants to set
      effluent standards for protecting aquatic organisms in Japan.
AB  - New environmental standards for protecting aquatic organisms for zinc (e.g., 0.03
      mg/L) in surface waters were set in Japan in 2003. Although wastewater effluent
      might be one of the major pathways of zinc to public water bodies in Japan,
      current status of concentration of zinc in wastewater effluent was not clear due
      to higher detection limits (e.g., 0.5 mg/L) than the level required by the new
      regulations. This study aims at assessing current status of zinc in wastewater
      effluent in Japan to revise wastewater effluent standards for protecting aquatic
      organisms. Survey of zinc in wastewater treatment plants (WWTPs) was carried out
      in Japan in 2005, setting the detection limits at least 0.01 mg/L. The results of
      the survey suggested the difficulty to remove zinc (especially dissolved zinc)
      with conventional activated sludge treatment if concentration of zinc in influent
      was relatively low. And it was suggested that high concentration of dissolved
      zinc might be derived from some industries discharging high concentration of
      zinc. The concentration of zinc in wastewater influent without industrial
      discharges was about 0.1 mg/L which might be lower than that in wastewater from
      industries discharging high concentration of zinc. Finally, effluent standards
      for point sources including WWTPs to public water bodies were set at 2 mg/L in
      2006. Based on the results of the survey that it was difficult to remove
      dissolved zinc discharged from industries at WWTPs, the effluent standards from
      industries to sewerage were set at the same value of the effluent standards from
      WWTPs to public water bodies.

PMID- 19757120
TI  - Impact assessment and decontamination of pesticides from meat under different
      culinary processes.
AB  - A total of 75 animals between 1.5 and 8 years old were randomly selected for the
      study. Of these, 57.8% were cross-bred animals and the rest were non-descript.
      Moreover, 61.8% of the animals under study were brought for slaughter from local
      sources and the rest from farm houses. Samples collected from five districts
      revealed contamination with traces of organochlorine pesticides (0.01-0.22 microg
      g(-1)) and organophosphorus pesticides (0.111-0.098 microg g(-1)). In general,
      all the raw meat samples possessed dichlorodiphenyltrichloroethane at the highest
      level. Contamination was highest in cow meat samples and lowest in chicken
      samples. No particular district-wise trend was obtained for the pesticides
      selected for analysis. Subsequent decontamination study revealed that cooking is
      the best option in reducing pesticide load in raw meat samples. Cooked chicken is
      the safest foodstuff for consumption.

PMID- 19757121
TI  - Study of temporal variation in ambient air quality during Diwali festival in
      India.
AB  - The variation in air quality was assessed from the ambient concentrations of
      various air pollutants [total suspended particle (TSP), particulate matter < or
      =10 microm (PM(10)), SO(2), and NO(2)] for pre-Diwali, Diwali festival, post
      Diwali, and foggy day (October, November, and December), Delhi (India), from 2002
      to 2007. The extensive use of fireworks was found to be related to short-term
      variation in air quality. During the festival, TSP is almost of the same order as
      compared to the concentration at an industrial site in Delhi in all the years.
      However, the concentrations of PM(10), SO(2), and NO(2) increased two to six
      times during the Diwali period when compared to the data reported for an
      industrial site. Similar trend was observed when the concentrations of pollutants
      were compared with values obtained for a typical foggy day each year in December.
      The levels of these pollutants observed during Diwali were found to be higher due
      to adverse meteorological conditions, i.e., decrease in 24 h average mixing
      height, temperature, and wind speed. The trend analysis shows that TSP, PM(10),
      NO(2), and SO(2) concentration increased just before Diwali and reached to a
      maximum concentration on the day of the festival. The values gradually decreased
      after the festival. On Diwali day, 24-h values for TSP and PM(10) in all the
      years from 2002 to 2007 and for NO(2) in 2004 and 2007 were found to be higher
      than prescribed limits of National Ambient Air Quality Standards and
      exceptionally high (3.6 times) for PM(10) in 2007. These results indicate that
      fireworks during the Diwali festival affected the ambient air quality adversely
      due to emission and accumulation of TSP, PM(10), SO(2), and NO(2).

PMID- 19757122
TI  - Risk assessment and chemical decontamination of an oxime carbamate insecticide
      (methomyl) from eggplant, Solanum melongena L.
AB  - Methomyl, S-methyl (EZ)-N-(methylcarbamoyloxy)thioacetimidate, is a systemic
      insecticide chosen for the management of shoot and fruit borer, Leucinodes
      orbonalis G. Codex Alimentarious Commission has proposed a maximum residue limit
      (MRL) of 0.2 mg kg( - 1) of methomyl, and there is a need to validate this value
      on eggplant. First + first-order model can explain the nonlinear dissipation
      pattern of methomyl conveniently in comparison to first-order kinetics. The
      preharvest intervals (PHI) of 27.3 and 35.3 days as obtained from first + first
      order model for single and double doses would bring down the methomyl residue
      below MRL in actual practice. The respective half-lives were 6.6 and 7.8 days. On
      the other hand, first-order model suggests methomyl dissipated with a half-life
      value around 5 days and proposed PHIs of 6.57 and 8.57 days for single and double
      doses, which was far from reality. Hence, five different decontamination agents
      were chosen for the decontamination of methomyl from eggplant. Safety factors
      such as theoretical maximum daily intake and maximum permissible intake were used
      to evaluate risk assessment to human health. A 3-day waiting period for the both
      doses, following conventional agricultural practice and processing factor could
      not ensure sufficient margin of safety. Subjecting the data to a processing
      factor of 60% could not bring the residues below the proposed MRL by Codex.
      Methomyl is not found appropriate and effective for application in eggplant.
      Either the proposed MRL needs to be revised or good agricultural practice
      involving methomyl for plant protection in eggplant cultivation is questioned.

PMID- 19757123
TI  - Trace metal concentrations in tissues of two tinamou species in mining areas of
      Bolivia and their potential as environmental sentinels.
AB  - Mining has a long history in the Bolivian Andes and has left many tailing piles,
      from which trace metals may reach surface waters, soils, and biota. The potential
      of tinamous (Birds: Tinamidae) as sentinels has never been tested before,
      although their biological and ecological characteristics mean they could well be
      appropriate bioindicators. We captured 13 and nine individuals of the Ornate
      Tinamou (Nothoprocta ornata) from two polluted sites (P1 and P2) and 10 and five
      from control unpolluted sites (NP1 and NP2) and used, for comparative purposes,
      four specimens bred in captivity. We also captured six specimens of Darwin's
      Nothura (Nothura darwinii) from the polluted site, P2. We determined the
      concentration of As, Cd, Pb, and Sb in feathers, liver, and kidney and conducted
      histological analyses of liver and kidney. For the Ornate Tinamou, a site effect
      was found for all trace metals in all tissues, with the highest concentrations at
      polluted sites. At the P2 site, no differences between the two tinamou species
      were detected except in some cases where Darwin's Nothura shows near-double
      concentrations. In some cases, mean and/or individual values of trace metal
      concentrations reached toxicity levels at the polluted sites. Thesaurismosis in
      proximal convoluted renal tubules, probably related to Cd exposure, was observed
      in 30% of the samples from the P1 site. Significant correlations were observed
      between all tissues for all trace metals and also for all trace metals in each
      tissue. Because the species studied are ubiquitous and relatively abundant, we
      recommend monitoring programs based on feather analysis.

PMID- 19757124
TI  - Characterization of PM10 and PM2.5 and associated heavy metals at the crossroads
      and urban background site in Zabrze, Upper Silesia, Poland, during the smog
      episodes.
AB  - The concentrations of seven heavy metals (Cd, Cr, Cu, Fe, Mn, Ni, and Pb)
      associated with PM10 and PM2.5 at the crossroads and the background sites have
      been studied in Zabrze, Poland, during smog episodes. Although the background
      level was unusually elevated due to both high particulate emission from the
      industrial and municipal sources and smog favorable meteorological conditions,
      significant increase of the concentration of PM2.5 and PM10 as well as associated
      heavy metals in the roadside air compared to the urban background has been
      documented. The average daily difference between the roadside and corresponding
      urban background aerosol concentration was equal to 39.5 microg m(-3) for PM10
      and 41.2 microg m(-3) for PM2.5. The highest levels of the studied metals in
      Zabrze appeared for iron carried by PM10 particles: 1,706 (background) and 28,557
      ng m(-3) (crossroads). The lowest concentration level (in PM10) has been found
      for cadmium: 7 and 77 ng m(-3) in the background and crossroads site,
      respectively. Also the concentrations of heavy metals carried by the fine
      particles (PM2.5) were very high in Zabrze during the smog episodes.
      Concentrations of all studied metals associated with PM10 increased at the
      roadside compared to the background about ten times (one order) while metals
      contained in PM2.5 showed two to three times elevated concentrations (except Fe
      five times and Cr-no increase).

PMID- 19757125
TI  - Monitoring of total and bioavailable heavy metals concentration in agricultural
      soils.
AB  - The aim of this paper is to evaluate total and bioavailable concentration of
      heavy metals in agricultural soils in order to estimate their distribution, to
      identify the possible correlations among toxic elements and the pollution
      sources, to distinguish the samples in relation to sampling site or to sampling
      depth, and to evaluate the available fraction providing information about the
      risky for plants. In particular, we reinvestigated total concentrations of As,
      Be, Cd, Cr, Cu, Fe, Hg, Mn, Ni, Pb, Sb, V, and Zn and available concentrations of
      As, Be, Cd, Cr, Cu, Hg, Ni, Pb, Sb, and Zn in soil from Apulia (Southern Italy).
      Analytical results showed that total concentrations, for all soils, are in the
      range permitted by regulations in force in Italy, but some soils evidence slight
      enrichment of Cd, Cr, Cu, Pb, and Zn. All the heavy metals in the available
      fraction were below the detection limits of the analytical techniques used except
      Cu, Ni, Pb, and Zn.

PMID- 19757126
TI  - Macrofaunal recolonisation following the intertidal placement of fine-grained
      dredged material.
AB  - Dredged material is increasingly being regarded as a potential resource, and one
      of its many uses is to create and/or improve intertidal habitats (i.e. beneficial
      use). However, uncertainties over the longer-term environmental consequences of
      such schemes have, to date, limited the practice to small-scale applications in
      UK waters. This paper studies the macrofaunal recolonisation of fine-grained
      dredged material recharged concurrently at four adjacent recharge areas along the
      south-east coast of the UK in order to facilitate predictions regarding the
      recolonisation of comparable schemes and, thereby, to promote effective
      environmental management. During the 2-year study period, the four recharge areas
      were distinctly different in terms of their environmental characteristics,
      primarily wave exposure and bed level. These conditions resulted in different
      macrofaunal recolonisation rates and community structures. While the low-level,
      wave-sheltered area experienced rapid recolonisation, the process was delayed
      until 12 months post-recharge at the relatively wave-exposed areas. Bed level
      differences resulted in distinctly different communities in wave-sheltered areas
      but not under wave-exposed conditions. While we are unable to separate the
      effects of individual environmental variables on recolonisation, these results
      provide general conclusions as to the importance of environmental conditions on
      resulting macrofaunal communities.

PMID- 19757127
TI  - Students generating questions for their own written examinations.
AB  - Assessment partnerships between staff and students are considered a vital
      component of the student-centred educational process. To enhance the development
      of this partnership in a problem-based learning curriculum, all first-year
      students were involved in generating a bank of formative assessment questions
      with answers, some of which were included in their final written examination.
      Important principles to guide development of a sound methodology for such an
      assessment partnership have been described. These include organisational issues
      as well as matters pertaining to participation, education and motivation of
      students and teaching staff.

PMID- 19757128
TI  - Effect of first-encounter pretest on pass/fail rates of a clinical skills medical
      licensure examination.
AB  - Due to the high-stakes nature of medical exams it is prudent for test agencies to
      critically evaluate test data and control for potential threats to validity. For
      the typical multiple station performance assessments used in medicine, it may
      take time for examinees to become comfortable with the test format and
      administrative protocol. Since each examinee in the rotational sequence starts
      with a different task (e.g., simulated clinical encounter), those who are
      administered non-scored pretest material on their first station may have an
      advantage compared to those who are not. The purpose of this study is to
      investigate whether pass/fail rates are different across the sequence of pretest
      encounters administered during the testing day. First-time takers were grouped by
      the sequential order in which they were administered the pretest encounter. No
      statistically significant difference in fail rates was found between examinees
      who started with the pretest encounter and those who encountered the pretest
      encounter later in the sequence. Results indicate that current examination
      administration protocols do not present a threat to the validity of test score
      interpretations.

PMID- 19757129
TI  - The use of objective structured self-assessment and peer-feedback (OSSP) for
      learning communication skills: evaluation using a controlled trial.
AB  - Feedback is essential to guide students towards expected performance goals. The
      usefulness of teacher feedback on improving communication skills (CS) has been
      well documented. It has been proposed that self-assessment and peer-feedback has
      an equally important role to play in enhancing learning. This is the focus of
      this study. Objectively structured self-assessment and peer feedback (OSSP) was
      incorporated into small group CS teaching sessions of a group of semester one
      medical students who were learning CS for the first time, to minimise the
      influence of previous educational interventions. A control group matched for
      academic performance, gender and age was used to enable parallel evaluation of
      the innovation. A reflective log containing closed and open ended questions was
      used for OSSP. Facilitators and simulated patients provided feedback to students
      in both groups during CS learning as per routine practice. Student perceptions on
      OSSP and acceptability as a learning method were explored using a questionnaire.
      CS were assessed in both groups using objective structured clinical examination
      (OSCE) as per routine practice and assessors were blinded as to which group the
      student belonged. Mean total score and scores for specific areas of interview
      skills were significantly higher in the experimental group. Analysis of the
      questionnaire data showed that students gained fresh insights into specific areas
      such as empathy, addressing patients' concerns and interview style during OSSP
      which clearly corroborated the specific differences in scores. The free text
      comments were highly encouraging as to acceptability of OSSP, in spite of 67%
      being never exposed to formal self- and peer-assessment during pre-university
      studies. OSSP promotes effective CS learning and learner acceptability is high.

PMID- 19757130
TI  - The second prolactin receptor in Nile tilapia (Oreochromis niloticus): molecular
      characterization, tissue distribution and gene expression.
AB  - Prolactin (PRL) is one of the most versatile hormones found in the pituitary of
      vertebrates and exerts its actions through binding to a specific PRL receptor
      (PRLR). Here we describe the cloning and characterization of a second prolactin
      receptor (ntPRLR2), isolated from the ovary of Nile tilapia (Oreochromis
      niloticus). The newly identified PRLR cDNA was 2011 bp in length and encoded 529
      amino acids. It shared 31.6% identity in nucleotide sequence and 29.2% in deduced
      amino acid sequence with the first PRLR identified in Nile tilapia (ntPRLR1).
      Both of these ntPRLRs resemble the long form mammalian PRLRs. The nominated
      ntPRLR2 was further confirmed as a real prolactin receptor based on its
      competence to transactivate the beta-casein and c-fos promoters in the
      transiently ntPRLR2-transfected HEK293 cells. The ntPRLR2 gene also found to
      encode a 864-bp short form transcript in the ovary, which was confirmed by
      Northern blot analysis. A tissue distribution study by real-time PCR revealed
      that the mRNA of both receptors (ntPRLR1 and ntPRLR2) was widely expressed in
      different tissues, with an extremely high abundance in the osmoregulatory organs,
      including the gills, intestine and kidney. ntPRLR1 mRNA was more abundant than
      ntPRLR2 in the testis, while the reverse expression pattern was found in the
      ovary. In the ovary, ntPRLR2 mRNA demonstrated a distinct gonadal development
      dependent expression profile, with significantly higher levels at a sexual mature
      stage than at sexual recrudescent and sexual regressed stages. When challenged
      with estradiol, ntPRLR2 mRNA expression was up-regulated by E2, whereas E2 had no
      significant effect on ntPRLR1.

PMID- 19757131
TI  - Haematological and blood biochemical characteristics of Glyptosternum maculatum
      (Siluriformes: Sisoridae) in Xizang (Tibet).
AB  - This study investigated the haematological and blood biochemical characteristics
      of Glyptosternum maculatum. The haematological and biochemical parameters were
      measured in 30 adult fish collected from Nyingchi Reach of Yarlung Zangbo River
      in Tibet. The red blood cell count (RBC), haemoglobin concentration (Hb),
      haematocrit (Hct), erythrocyte osmotic fragility (maxEof and minEof), the
      erythrocyte sedimentation rate, mean cell volume (MCV), mean cellular haemoglobin
      content (MCH), and mean cell haemoglobin concentration (MCHC) were determined.
      Compared with other Siluriformes fishes, G. maculatum showed similar mean values
      for Hct, Hb, MCH, and MCHC and had slightly lower RBC and higher MCV. The
      biochemical parameters were assayed including alanine aminotransferase, aspartate
      aminotransferase (AST), alkaline phosphatase, total protein, albumin, globulin,
      albumin/globulin ratio, total bilirubin, direct bilirubin, urea, creatinine,
      glucose, total cholesterol, and triglyceride. The result showed that the value of
      AST in G. maculatum was obviously higher than that in Rhamdia quelen as well as
      in Silurus merdionalis.

PMID- 19757132
TI  - Morphology and changes of chloride cell of Rutilus rutilus Caspicus (Cyprinidea,
      teleost) in Caspian Sea.
AB  - An ultrastructural study was performed on chloride cells of euryhaline
      R.r.Caspicus of south of Caspian Sea. The chloride cells are distributed in the
      interlamellar region of filaments. They are oval to elongated form with an apical
      positioned nucleus, expanded tubular system and heteromorphic mitochondria. These
      cells are surrounded by pavement cell and accessory cell. A small and depressed
      surface formed by pavement cells is in contact with the aquatic milieu. There is
      also channel system in accessory cells. One of the typical features was the
      important changes in microtubules and mitochondria of chloride cells in some
      fishes. Swelling and rupture of cristae and degeneration of microtubules were
      from these changes.

PMID- 19757133
TI  - Problem formulation in the environmental risk assessment for genetically modified
      plants.
AB  - Problem formulation is the first step in environmental risk assessment (ERA)
      where policy goals, scope, assessment endpoints, and methodology are distilled to
      an explicitly stated problem and approach for analysis. The consistency and
      utility of ERAs for genetically modified (GM) plants can be improved through
      rigorous problem formulation (PF), producing an analysis plan that describes
      relevant exposure scenarios and the potential consequences of these scenarios. A
      properly executed PF assures the relevance of ERA outcomes for decision-making.
      Adopting a harmonized approach to problem formulation should bring about greater
      uniformity in the ERA process for GM plants among regulatory regimes globally.
      This paper is the product of an international expert group convened by the
      International Life Sciences Institute (ILSI) Research Foundation.

PMID- 19757134
TI  - Physiological change in camel milk composition (Camelus dromedarius) 1. Effect of
      lactation stage.
AB  - The change in the composition of camel milk in four dromedaries was studied by
      including the common measured parameters: protein, total fat, lactose, main
      minerals (calcium, phosphorus, and iron), and vitamin C. The fat matter varied
      from 4.34% to 7.81% with a slight decrease all along the lactation and a minimal
      value at the 14th week corresponding to the lactation peak. Those variations were
      less important for protein content (from 2.58% to 3.64%), but the minimal value
      was observed at the 14th week also. The lactose varied slightly around its mean
      of 3.46%. The vitamin C concentration varied from 48 to 256 mg/l with a tendency
      of increasing all along the lactation. Calcium and phosphorus concentrations were
      quite parallel and their ratio Ca/P was constant. The minimal values (1.43 g/l
      for calcium and 1.16 g/l for phosphorus) were observed at the beginning of the
      lactation. The iron concentrations varied around the mean of 1.73 mg/l.

PMID- 19757135
TI  - Comparison of different testing schemes to increase the detection Mycobacterium
      bovis infection in Ethiopian cattle.
AB  - Host immune responses to Mycobacterium bovis (M. bovis) infection are variable at
      the different severity stages of pathology of the disease. In countries like
      Ethiopia, where routine screening of bovine TB is not undertaken, the use of
      tests which measure cellular and antibody responses may help for the maximum
      detection of infection. In the present study, 701 cattle were tested for bovine
      tuberculosis (BTB) using comparative intradermal tuberculin (CIDT) test,
      interferon (IFN)-gamma test, and lateral flow assay. The apparent prevalence was
      32% when all the three tests were used, but varied from 23 to 25% when a pair of
      tests was used and from 9% to 15% when a single test was used. Agreement was
      observed between CIDT and IFN-gamma tests both at a cut-off >2 mm (Kappa +/-
      standard Error, k +/- SE, 0.129 +/- 0.045; 95%CI = 0.041,0.216) and a cut-off >4
      mm (k +/- SE, 0.094 +/- 0.044, 95%CI = 0.008,0.179) while no agreement was
      observed either between CIDT test and lateral flow assay (k +/- SE, -0.04 +/-
      0.033; 95%CI = -0.104,0.024) or between IFN-gamma tests and lateral flow assay (k
      +/- SE, -0.031 +/- 0.032; 95% CI = -0.093,0.031). Thus, the use of more than one
      test leads to the detection of the maximum number of infected animals.

PMID- 19757136
TI  - Unusual cause of proteinuria and re-renal failure after kidney transplantation:
      de novo localized AL amyloidosis in renal allograft.
AB  - Amyloidosis results from the deposition of amyloid proteins in organ and tissues.
      It can be systemic or localized. Localized primary amyloidosis in renal allograft
      is an extremely rare clinical condition. We describe here a 46-year-old man who
      developed proteinuria and re-renal failure 5 years after receiving deceased renal
      allograft and proved to be a case of isolated primary AL amyloidosis in renal
      allograft confirmed by clinical investigations and renal biopsy.

PMID- 19757138
TI  - Purification and biochemical characterization of a novel alpha-glucosidase from
      Aspergillus niveus.
AB  - An extracellular a-glucosidase produced by Aspergillus niveus was purified using
      DEAE-Fractogel ion-exchange chromatography and Sephacryl S-200 gel filtration.
      The purified protein migrated as a single band in 5% PAGE and 10% SDS-PAGE. The
      enzyme presented 29% of glycosylation, an isoelectric point of 6.8 and a
      molecular weight of 56 and 52 kDa as estimated by SDS-PAGE and Bio-Sil-Sec-400
      gel filtration column, respectively. The enzyme showed typical alpha-glucosidase
      activity, hydrolyzing p-nitrophenyl alpha-D-glucopyranoside and presented an
      optimum temperature and pH of 65 degrees C and 6.0, respectively. In the absence
      of substrate the purified alpha-glucosidase was stable for 60 min at 60 degrees
      C, presenting t(50) of 90 min at 65 degrees C. Hydrolysis of polysaccharide
      substrates by alpha-glucosidase decreased in the order of glycogen, amylose,
      starch and amylopectin. Among malto-oligosaccharides the enzyme preferentially
      hydrolyzed malto-oligosaccharide (G10), maltopentaose, maltotetraose, maltotriose
      and maltose. Isomaltose, trehalose and beta-ciclodextrin were poor substrates,
      and sucrose and alpha-ciclodextrin were not hydrolyzed. After 2 h incubation, the
      products of starch hydrolysis measured by HPLC and thin layer chromatography
      showed only glucose. Mass spectrometry of tryptic peptides revealed peptide
      sequences similar to glucan 1,4-alpha-glucosidases from Aspergillus fumigatus,
      and Hypocrea jecorina. Analysis of the circular dichroism spectrum predicted an a
      helical content of 31% and a beta-sheet content of 16%, which is in agreement
      with values derived from analysis of the crystal structure of the H. jecorina
      enzyme.

PMID- 19757139
TI  - Continuing education needs assessment of pharmacists in the United Arab Emirates.
AB  - OBJECTIVE: The main objective of this study was to offer an insight on the issue
      of continuing education (CE) in the UAE and to determine the type and format of
      CE pharmacists in this country prefer to attend and consider most effective.
      METHODS: A multi-theme survey was developed to find the reasons pharmacists
      choose to attend different CE programs, the survey assessed continuing education
      needs and preferences of pharmacists. Survey items included the types of formats
      and topics pharmacists prefer to attend and think are most useful to enhance
      their knowledge and skill. Finally the survey explored some barriers pharmacists
      conceive as such to attending effective CE. RESULTS: One hundred thirty-two
      surveys were included in this study, the vast majority of the participants were
      bachelor's degree holders who were 40 years and younger. The participant's main
      types of employment were marketing and hospital practice. Pharmacists'
      preferences as for the format and topic type for programs they would like to
      attend were identified and compared to other practice settings. Barriers to
      attending effective CE programs were also elicited. CONCLUSION: Interactive
      workshops were recognized as the most favorable format for CE in this study,
      computer and internet-based formats were also ranked highly by participants
      followed by live-in person and printed material-based programs. Topics covering
      innovations in pharmacy practice and disease management were at the top of
      priorities for pharmacists who would also like to see more certificate programs
      be offered to them.

PMID- 19757141
TI  - Paralytic ileus possibly associated with interaction between ritonavir/lopinavir
      and vincristine.
AB  - CASE DESCRIPTION: A French Caucasian man aged 39 with HIV infection was treated
      with abacavir/lamivudine and ritonavir/lopinavir. The patient (normal renal and
      liver functions) was diagnosed with a Burkitt lymphoma for which he was treated
      with cyclophosphamide day 1 to 5; doxorubicin day 1; methotrexate day 10; and
      vincristine day 1 and 8. At day 12, he suffered from abdominal pain associated
      with constipation. Paralytic ileus was diagnosed by study imaging. Ileus lasted
      10 days necessitating parenteral feeding. Later on, a further cycle of
      chemotherapy with etoposide replacing vincristine was given and was well
      tolerated. CONCLUSION: We speculate that an interaction between
      ritonavir/lopinavir and vincristine was responsible for this severe toxicity.
      Vincristine is transported by P-gp and is metabolized via CYP3A5. Ritonavir is a
      potent CYP3A5 isoenzyme and P-gp inhibitor. Lopinavir is also a P-gp inhibitor.
      Ritonavir and lopinavir might have delayed vincristine elimination. Clinicians
      should be aware of this possible interaction.

PMID- 19757142
TI  - Care of the stroke patient-communication between the community pharmacist and
      prescribers in the Republic of Ireland.
AB  - OBJECTIVE: This study sought to examine the perceptions that community
      pharmacists have of communication with prescribers in both primary and secondary
      care in Ireland, with respect to care of stroke patients. SETTING: Community
      pharmacies across Ireland, stratified into the four representative administrative
      regions. METHOD: Survey using a structured postal questionnaire. MAIN OUTCOME
      MEASURE: Perceptions of communication with prescribers based in primary and
      secondary care; pharmacy and pharmacy premises demographics. RESULTS: A response
      rate of 52% (n = 314) was achieved. Community pharmacists' perceptions of
      information provision from secondary care were low, the majority (83%) never
      received any information from the hospital, although they would welcome it.
      Communication with hospital based prescribers was considered by most (93%) to be
      poor. The majority (greater than 75%) of respondents expressed a desire for
      greater information provision concerning a stroke patient's medication and
      diagnostic information. Pharmacists' perceptions of interaction with general
      practitioners were generally regarded as good (63%) although information
      provision in both directions between pharmacist and general practitioner could be
      improved. CONCLUSION: The findings of this study indicated that community
      pharmacists perceive that there is room for improvement in the communication
      between themselves and prescribers in the primary and secondary care settings,
      concerning the care of the stroke patient. This highlights the need for the
      development of formal communication channels between community pharmacists and
      other members of the healthcare team involved in the care of the stroke patient.
      However, the challenges of communicating patient information across healthcare
      sectors are recognized.

PMID- 19757143
TI  - Introduction to imaging methods in photosynthesis.

PMID- 19757144
TI  - Neurometabolic disorders.

PMID- 19757145
TI  - Cardiomyopathy in the congenital disorders of glycosylation (CDG): a case of late
      presentation and literature review.
AB  - The congenital disorders of glycosylation (CDG) are a recently described group of
      inherited multisystem disorders characterized by defects predominantly of N- and
      O-glycosylation of proteins. Cardiomyopathy in CDG has previously been described
      in several subtypes; it is usually associated with high morbidity and mortality
      and the majority of cases present in the first 2 years of life. This is the first
      case with presentation in late childhood and the article reviews current
      literature. An 11-year-old female with a background of learning difficulties
      presented in cardiac failure secondary to severe dilated cardiomyopathy. Prior to
      the diagnosis of CDG, her condition deteriorated; she required mechanical support
      (Excor Berlin Heart) and was listed for cardiac transplant. Investigations
      included screening for glycosylation disorders, and isoelectric focusing of
      transferrin revealed an abnormal type 1 pattern. Analysis of phosphomannomutase
      and phosphomannose isomerase showed normal enzyme activity, excluding PMM2 (CDG
      Ia) and MPI (CDG Ib). Lipid-linked oligosaccharide and mutational studies have
      not yet defined the defect. Despite aggressive therapy there were persistent
      difficulties achieving adequate anticoagulation and she developed multiple life
      threatening thrombotic complications. She was removed from the transplant list
      and died from overwhelming sepsis 5 weeks following admission. This case
      emphasizes the need to screen all children with an undiagnosed cardiomyopathy for
      CDG, regardless of age, and where possible to exclude CDG before the use of
      cardiac bridging devices. It highlights the many practical and ethical challenges
      that may be encountered where clinical knowledge and experience are still
      evolving.

PMID- 19757146
TI  - Retinal detachment causing unilateral blindness in a 12-year-old  girl with
      gyrate atrophy.

PMID- 19757147
TI  - High incidence of profound biotinidase deficiency detected in newborn screening
      blood spots in the Somalian population in Minnesota.
AB  - Newborns identified with profound biotinidase deficiency (BTD) by the Minnesota
      Newborn Screening Program (MN NBS) between 1 October 2004 and 30 May 2008 were
      all from new immigrant groups. Thirty-three positive cases of BTD were identified
      out of 264 727 infants screened by the Wolf colorimetric system during the period
      of this study by MN NBS. Five cases of profound BTD (0.1 to <0.6 nmol/min per ml)
      and 26 cases of partial BTD (0.9 to 2.3 nmol/min per ml) were later confirmed
      through measurement of serum biotinidase activity. The incidence of combined
      partial and profound BTD of 1/8540 and that of profound BTD of 1/52 945 in
      Minnesota are unusually high in comparison with the reported worldwide numbers of
      1/61 067 for combined BTD and 1/137 401 for profound BTD. Four out of the 5 cases
      of profound BTD ascertained in the MN NBS cohort were of Somali ethnic
      background, and the remaining case was of Asian (Pakistani/Indian) ethnic
      background. All four Somali patients have the P497S mutation, with one of the
      four being homozygous for the mutation. The three compound heterozygotes all have
      a novel mutation (P142T) and two of them have another change (Y428Y) that has
      never been described. Within the last two decades, Minnesota has become home to
      an estimated 40 000 Somali immigrants and their children (<1% of the total
      Minnesota population). New population demographics prompt careful analysis of
      case cohorts to identify specific groups at risk for rare inborn errors of
      metabolism.

PMID- 19757148
TI  - Limited value of digital subtraction angiography in the evaluation of cell-based
      therapy in patients with limb ischemia.
AB  - Cell-based therapy has been proposed as a novel strategy for patients with severe
      peripheral arterial disease by stimulating vascular growth. In clinical studies
      of this therapy, the emphasis has been on demonstrating recovery of clinical
      parameters, rather than on evaluation of blood flow recovery. Angiography is
      still the gold standard for the assessment of lower leg arteries. Therefore, we
      studied the usefulness of angiography in the evaluation of cell-based therapy.
      Sixteen patients with critical leg ischemia (ischemic rest pain or ulcers), or
      persistent (>12 months) profound disabling claudication were unilaterally treated
      with autologous bone marrow-derived mononuclear cells. Pre- and 6 months post
      treatment digital subtraction angiographies (DSA) were assessed and compared in a
      blinded fashion twice by a panel of seven vascular surgeons and interventional
      radiologists. Inter- and intraobserver variability on qualitative
      (poor/moderate/rich) and semi-quantitative (increase/no difference/decrease)
      assessment of collateral circulation were evaluated. Agreement was expressed
      inter- and intraclass correlation coefficients (CC). Inter- and intraobserver
      agreement was moderate for the qualitative grading of collateral extent (CC =
      0.46 and 0.60, respectively). Agreement was moderate (inter-CC = 0.60) to good
      (intra-CC = 0.73) for comparing pre- and post-treatment DSA. Clinical response
      was based on limb salvage, pain-free walking distance, ankle-brachial pressure
      index and pain scores. No difference was observed in the extent of collateral
      circulation between pre- and post treatment DSA after separate analysis of
      clinical responding and non-responding patients (P = 0.92). DSA is not a suited
      modality for the evaluation of therapeutic angiogenesis.

PMID- 19757149
TI  - Evaluation of vascular reactivity of young male hypogonadotrophic hypogonadism
      patients.
AB  - We aimed to study the vascular reactivity of young male hypogonadal hypogonadism
      patients without any cardiovascular risk factors and compare these findings with
      the ones of age-matched healthy controls. Study population consisted of 26 young
      male hypogonadotrophic hypogonadism patients (20.9 +/- 1.3 years) and 25 age
      matched healthy male controls (21.8 +/- 2.9 years, P = NS). In addition to
      detailed hormonal analysis, each subject underwent ultrasound study of right
      brachial artery. Vessel diameter was measured at rest, during reactive hyperemia
      [endothelium-dependent flow-mediated vasodilation (FMD)] and after sublingual
      nitroglycerin administration (endothelium-independent vasodilation). Both flow
      mediated and endothelium-independent sublingual nitroglycerin mediated dilatation
      values of patients were higher compared to controls (12.98 +/- 10.76% vs. 7.92 +/
      1.96%, P = 0.003 and 21.44 +/- 10.36% vs. 14.72 +/- 3.57%, P = 0.023,
      respectively). Linear regression analysis revealed that only serum HDL levels
      (relative risk 2.94, 95% CI 0.12-0.66, P = 0.006) and baseline vessel diameter
      (relative risk -2.77, 95% CI -17.73 to -2.70, P = 0.009) were found to be
      independently associated with FMD values. Endogenous male sex hormones seem to
      exert negative effects on vascular reactivity parameters and much of their
      effects are indirect that is by the way of alteration on lipid profile.

PMID- 19757150
TI  - Intra-observer and interobserver variability of biventricular function, volumes
      and mass in patients with congenital heart disease measured by CMR imaging.
AB  - Cardiovascular magnetic resonance (CMR) imaging provides highly accurate
      measurements of biventricular volumes and mass and is frequently used in the
      follow-up of patients with acquired and congenital heart disease (CHD). Data on
      reproducibility are limited in patients with CHD, while measurements should be
      reproducible, since CMR imaging has a main contribution to decision making and
      timing of (re)interventions. The aim of this study was to assess intra-observer
      and interobserver variability of biventricular function, volumes and mass in a
      heterogeneous group of patients with CHD using CMR imaging. Thirty-five patients
      with CHD (7-62 years) were included in this study. A short axis set was acquired
      using a steady-state free precession pulse sequence. Intra-observer and
      interobserver variability was assessed for left ventricular (LV) and right
      ventricular (RV) volumes, function and mass by calculating the coefficient of
      variability. Intra-observer variability was between 2.9 and 6.8% and
      interobserver variability was between 3.9 and 10.2%. Overall, variations were
      smallest for biventricular end-diastolic volume and highest for biventricular end
      systolic volume. Intra-observer and interobserver variability of biventricular
      parameters assessed by CMR imaging is good for a heterogeneous group of patients
      with CHD. CMR imaging is an accurate and reproducible method and should allow
      adequate assessment of changes in ventricular size and global ventricular
      function.

PMID- 19757151
TI  - Intramyocardial hemorrhage and microvascular obstruction after primary
      percutaneous coronary intervention.
AB  - Reperfusion may cause intramyocardial hemorrhage (IMH) by extravasation of
      erythrocytes through severely damaged endothelial walls. The purpose of the study
      was to evaluate the clinical significance of IMH in relation to infarct size,
      microvascular obstruction (MVO) and function in patients after primary
      percutaneous intervention. Forty-five patients underwent cardiovascular MR
      imaging (CMR) 1 week and 4 months after primary stenting for a first acute
      myocardial infarction. T2-weighted spin-echo imaging (T2W) was used to assess
      infarct related edema and IMH, and delayed enhancement (DE) was used to assess
      infarct size and MVO. Cine CMR was used to assess left ventricular volumes and
      function at baseline and at 4 months follow-up. In 22 (49%) patients, IMH was
      detected as areas of attenuated signal in the core of the high signal intensity
      region on T2W images. Patients with IMH had larger infarcts, higher left
      ventricular volumes and lower ejection fraction. Contrast-to-noise ratio (CNR)
      between hyperintense periphery and the hypo-intense core of the T2W ischemic area
      correlated to peak CKMB, total infarct size and MVO size. Using univariable
      analysis, CNR predicted ejection fraction at baseline (beta = -0.62, P = 0.003)
      and follow-up (beta = -0.84, P < 0.001). However, after multivariable analysis,
      baseline ejection fraction and presence of MVO were the only parameters that
      predicted functional changes at follow-up. IMH was found in the majority of
      patients with MVO after reperfused myocardial infarction. It was closely related
      to markers of infarct size, MVO and function, but did not have prognostic
      significance beyond MVO.

PMID- 19757152
TI  - Determination of right ventricular end systole by cardiovascular magnetic
      resonance imaging: a standard method of selection.
AB  - For reproducible measurements of right ventricular (RV) volume and function, it
      may be important to use a consistent method to identify end systole (ES). We
      determined whether a significant difference exists between RV volumes measured
      using varying criteria from previous studies to define the timing of ES. In three
      normal subjects and nine patients with congenital heart disease, we measured RV
      volume from 3D reconstructions generated from 12 short and long axis magnetic
      resonance images (MRI). Cine frames analyzed included two frames before and three
      frames following ES, which we determined as the frame in which chamber area was
      most frequently minimum. ES coincided with onset of aortic valve closure in ten
      of 12 subjects; complete closure occurred 1 frame later. The tricuspid valve
      began to open 1-2 frames after ES, and completely opened 2-4 frames after ES. RV
      volume was unchanged between ES and the frame following. However, ES volume
      differed significantly from volume measured 1 or 2 frames before ES and from
      volume measured 2 or 3 frames following ES, although these volume differences lay
      within the range of observer variability. The time of minimum RV area in the 4
      chamber view agreed closely with that of ES (intraclass correlation coefficient =
      0.962). We conclude that minimum RV area in the 4-chamber view is a convenient
      marker of use for ES, and that aortic valve closure or onset of tricuspid valve
      opening could also be used, being unlikely to result in clinically significant
      errors.

PMID- 19757153
TI  - Production of antifungal cellobiose lipids by Trichosporon porosum.
AB  - The yeast Trichosporon porosum suppresses growth of ascomycetes and
      basidiomycetes belonging to 52 genera. It is due to secretion of a thermostable
      fungicidal agent. The suppression was maximal at pH 3.5-4.0. Fungicidal
      preparation obtained from the culture broth was shown to be a mixture of
      cellobiosides of dihydrodecane acid with different degree of acetylation of
      cellobiose residue. The preparation caused the death of Candida albicans and
      Filobasidiella neoformans cells in the concentrations of 0.2 and 0.03 mM,
      respectively.

PMID- 19757154
TI  - PhiC31 integrase interacts with TTRAP and inhibits NFkappaB activation.
AB  - Phage PhiC31 integrase-mediated gene delivery is believed to be safer than using
      retroviral vectors since the protein confines its insertion of the target gene to
      a limited number of sites in mammalian genomes. To evaluate its safety in human
      cells, it is important to understand the interactions between this integrase and
      cellular proteins. Here we show that PhiC31 integrase interacts with TTRAP as
      presented by yeast two-hybrid and co-immunoprecipitation assays. Reducing the
      expression of endogenous TTRAP can increase the efficiency of PhiC31 integrase
      mediated integration. A possible effect of interaction between PhiC31 integrase
      and TTRAP was highlighted by the fact that PhiC31 integrase inhibited the
      NFkappaB activation mediated by IL-1 in a dose-dependent manner. Because low dose
      of PhiC31 integrase can mediate considerable recombination events, we suggest
      that low dose of PhiC31 integrase be used when this integrase is applied in human
      cells.

PMID- 19757155
TI  - Protective effects of remifentanil on septic mice.
AB  - This study is to explore the effect of remifentanil on inducible nitric oxide
      synthase (iNOS) expression, IL-6 and IL-10 levels, myeloperoxidase (MPO)
      activity, white blood cell count in bronchoalveolar (BALF), ALT and AST activity
      in septic mice. Forty male KM mice were randomly divided into four groups, sham
      group, cecal ligation and puncture group (CLP group), remifentanil treatment
      group (R1 group), and remifentanil control group (R2 group). The mouse model of
      CLP was used to observe ALT and AST activity, white blood cell count in BALF and
      myeloperoxidase (MPO). IL-6 and IL-10 in lung and liver tissue were assayed by
      enzyme-linked immunosorbent assay (ELISA). Lung and liver tissues were harvested
      for determination of iNOS expression by Western blot analysis. The pathologic
      changes were observed under electron microscope. Compared with sham group, iNOS
      protein expression, white blood cell count in BALF, ALT and AST activity, MPO
      activity, IL-6 and IL-10 levels were markedly increased in CLP group. Compared
      with CLP group, iNOS protein expression, IL-6 and IL-10 levels, white blood cell
      count in BALF, ALT and AST activity, MPO activity of R1 group were significantly
      lower. The pathologic changes induced by sepsis were significantly attenuated by
      remifentanil under electron microscope. Remifentanil could suppress inflammatory
      responses and inhibit iNOS expression in septic mice. Remifentanil might have a
      protective effect against sepsis. Its action mechanisms are probably involved in
      the inhibition of inflammatory factor production and suppression of iNOS
      expression.

PMID- 19757156
TI  - A PCR-based SNP marker for specific authentication of Korean ginseng (panax
      ginseng) cultivar "Chunpoong".
AB  - Korean ginseng (Panax ginseng) has been developed as a horticultural crop due to
      the increasing demand in the world market. "Chunpoong" is an economically
      important cultivar with superior quality and high yield among nine cultivars of
      Korean ginseng. The aim of this work was to develop a simple technique for
      specific authentication of Chunpoong using DNA method. Molecular authentication
      of Chunpoong was investigated using DNA sequences of mitochondrial cytochrome
      oxidase subunit 2 (cox2) intron I and intron II regions. A single nucleotide
      polymorphism (SNP) specific to Chunpoong was detected and amplification
      refractory mutation system (ARMS)-PCR method was applied to specific
      identification of Chunpoong based on the SNP site. Ginseng samples collected from
      other locations were used to validate the SNP marker and the established method
      was determined to be effective. Thus, this work provides a rapid and reliable
      method for the specific identification of Chunpoong cultivar.

PMID- 19757157
TI  - Transcriptional regulation of human mucin gene MUC4 in pancreatic cancer cells.
AB  - The human mucin gene MUC4 is overexpressed in pancreatic cancer and cancer cell
      lines, while remaining undetectable in the normal pancreas, indicating its
      important role in pancreatic cancer pathogenesis. The molecular mechanisms
      involved in the regulation of MUC4 gene expression are not fully understood. In
      this report, we used pancreatic cancer cell line (Bxpc-3) to explore the
      potential transcription factors regulating MUC4 transcriptional activity. Through
      promoter screening, overexpressing methods and luciferase reporter studies, we
      found that transcription factors CREB, Ets-1, Elk-1 and STAT1 can positively
      regulate MUC4 expression at the promoter and mRNA level. Our findings will be
      helpful for better understanding the transcriptional regulation of MUC4 in
      pancreatic cancer cells and identifying key biologically relevant factors that
      may account for its aberrant expression in pancreatic cancer.

PMID- 19757158
TI  - Cloning and characterization of a wheat beta-1,3-glucanase gene induced by the
      stripe rust pathogen Puccinia striiformis f. sp. tritici.
AB  - b-1,3-Glucanases are a group of pathogenesis related proteins that have been
      reported to be involved in plant defense against pathogens in many other plant
      pathogen systems. However, it was not clear if these genes play similar role in
      wheat (Triticum aestivum L.) against Puccinia striiformis f. sp. tritici (Pst),
      the stripe rust pathogen. To investigate the role of b-1,3-glucanase (EC3.2.1.39)
      in the resistance response of wheat (cv. Suwon11) to stripe rust, a wheat b-1,3
      glucanase gene induced by Pst, designated as TaGlu, was cloned and
      characterized.TaGlu was predicted to encode a basic protein of 334 amino acids.
      Quantitative real-time PCR analyses revealed that the transcription of TaGlu was
      induced during both compatible and incompatible interactions with Pst, but the
      transcription level was much higher in the incompatible interaction than that in
      the compatible interaction. TaGlu also showed noticeable induction of gene
      expression in young green leaf tissues treated with salicylic acid, methyl
      jasmonate or ethylene. Immunogold labeling assays showed that the enzyme were
      localized mainly in the host cell wall and over the extra haustorial matrix, and
      the labeling densities were found significantly higher in the incompatible
      interaction than those in the compatible interaction.

PMID- 19757159
TI  - Molecular cloning and expression analysis of an F-box protein gene responsive to
      plant hormones in Brassica napus.
AB  - F-box protein family is characterized by an F-box motif that has been shown to be
      critical for the controlled degradation of regulatory proteins. In plant, F-box
      protein plays an important role in signal pathways and involved in various signal
      transduction systems. A full-length cDNA encoding a putative F-box protein,
      designated as BnSLY1, was isolated from Brassica napus. The full-length cDNA of
      BnSLY1 was 809 bp containing a 438 bp open reading frame encoding a precursor
      protein of 138 amino acid residues. Comparative and bioinformatic analyses
      revealed that BnSLY1 showed high degree of homology with F-box proteins from
      other plant species and contained F-box, GGF and LSL conserved motifs. The
      expression of BnSLY1 under exogenous gibberellins acid-3 (GA3), abscisic acid
      (ABA) and GA biosynthetic inhibitor paclobutrazol (PAC) was analyzed using real
      time PCR. The results showed that the expression of BnSLY1 was down-regulated
      after GA3 treatment and prominently induced by ABA in the low concentrations.
      Moreover, BnSLY1 was also induction in the high concentrations of PAC. These
      results suggest that the expression of BnSLY1 was regulated by the exogenous GA3,
      ABA and PAC and may be related to endogenous level of GA in B. napus.

PMID- 19757160
TI  - Regulation of GSK-3 beta in the proliferation and apoptosis of human thyrocytes
      investigated using a GSK-3 beta-targeting RNAi adenovirus expression vector:
      involvement the Wnt/beta-catenin pathway.
AB  - Disorders in the proliferation and apoptosis of thyrocytes may induce goitre,
      adenoma and carcinoma in the thyroid. The Wnt/beta-catenin pathway has been
      demonstrated to be involved in the regulation of cell proliferation,
      differentiation and apoptosis in various cell lines. The regulatory mechanism on
      the proliferation and differentiation of thyrocytes is not well characterized. In
      the present study, a GSK-3beta-targeting RNA interference (RNAi) adenovirus
      vector was constructed and delivered to primary human thyrocytes. Results showed
      that the expression of beta-catenin protein in primary human thyrocytes was
      increased after GSK-3beta-targeting RNAi adenovirus infection, the proliferation
      of primary human thyrocytes was significantly stimulated using Bromodeoxyuridine
      (BrdU) assay, while cell apoptosis was slightly affected which was observed
      through flow cytometry. It is concluded that the Wnt/beta-catenin pathway plays a
      significant role in the regulation of the proliferation of primary human
      thyrocytes.

PMID- 19757161
TI  - CD1d gene is a target for a novel amplicon at 1q22-23.1 in human  hepatocellular
      carcinoma.
AB  - Genome copy number variation (CNV) is one of the mechanisms to regulate the
      expression level of genes which contributes to the development and progression of
      cancer. In order to investigate the regions of high-level amplification and
      potential target genes within these amplicons in hepatocellular carcinoma (HCC),
      we analyzed HCC cell line (TJ3ZX-01) for CNV regions at the whole genome level
      using GeneChip Human Mapping 500K array, and also examined the relative copy
      number and expression levels of the related genes at candidate amplicons in 41
      HCC tissues via real-time fluorescence quantitative PCR methods. Through analysis
      of sequence tag site(STS) markers by quantitative PCR, The two candidate
      amplicons at 1q found by SNP array were shown to occur in56.1% (23/41) HCC
      samples at 1q21 and 80.5% (33/41) at 1q22-23.1. Wilcoxon signed rank test showed
      expression of CD1d, which located at amplicon of 1q22-23.1 increased
      significantly within tumor tissues compared with paired nontumor tissues. Our
      study provides evidences that a novel, high-level amplicon at 1q22-23.1 occurs in
      both HCC cell line and tissues. CD1d is a potential target for this amplicon in
      HCC. The up-regulation of CD1d may be used as a novel molecular signature for
      diagnosis and prognosis of HCC.

PMID- 19757162
TI  - Characterization of a novel human HMBOX1 splicing variant lacking the homeodomain
      and with attenuated transcription repressor activity.
AB  - We previously identified the human HMBOX1 (homeobox containing 1) gene, which
      represents a distinct group of HNF transcription factors, and is a potential
      transcription repressor with highly expression in pancreas. In our present work,
      we found that there exists a splicing variant of HMBOX1, designated HMBOX1b.
      Compared to HMBOX1, HMBOX1b encodes a 304 amino acids protein that shares the N
      terminal region but has no homeodomain and the C-terminal region because of an
      alternative exon 7 which results in reading frame shifting. Unlike the highly
      pancreatic expression of HMBOX1, HMBOX1b was ubiquitous expressed in all human
      tissues detected by RT-PCR. Immunofluorescence staining showed that HMBOX1b
      accumulated in both cytoplasm and nucleus, and transcriptional reporter assays
      indicated that HMBOX1b only retained faint transcriptional repressive activity.
      Taken together, our findings suggest a distinct role of HMBOX1b, and the control
      of mRNA splicing might be involved in homeobox genes regulation.

PMID- 19757163
TI  - A hybrid promoter-containing vector for direct cloning and enhanced expression of
      PCR-amplified ORFs in mammalian cells.
AB  - An efficient vector, designated as pCAGX, was designed for direct cloning and
      enhanced expression of PCR-amplified ORFs in mammalian cells. It relied on the
      well-known TA-cloning principle, and utilized the CMV enhancer/chicken beta
      actin/rabbit beta-globin (CAG) hybrid promoter instead of the classical CMV
      promoter to drive more efficient transgene expression in wider host cells. The
      specially designed cassette under CAG hybrid promoter contained two tandemly
      arrayed XcmI sites which were spaced by an additional EcoRV site. For direct
      cloning and expressing PCR-amplified ORFs, the T-vector was prepared by further
      digesting the EcoRV-linearized pCAGX with XcmI to produce T tails on both 3'
      ends, which could efficiently minimize the non-recombinant background of T-vector
      and eliminate the necessity of selective marker genes such as LacZ that allowed
      blue/white screening. Various PCR fragments in length were prepared to verify the
      cloning efficiency by ligation with this vector, and GFP gene expression under
      control of the CAG hybrid promoter in different host cells was assayed by flow
      cytometry. The results indicated that this vector was higher efficient,
      especially suitable for cloning and expressing a number of interesting ORFs in
      parallel, and higher-level transgene expression in different mammalian cells was
      obtained than the reported vectors using the CMV promoter.

PMID- 19757164
TI  - Constructing glucagon like peptide-1 receptor fused with derivatives of GFP for
      visualizing protein-protein interaction in living cells.
AB  - The glucagon-like peptide-1 receptor (GLP-1 receptor) mediates important
      antidiabetogenic effects on peripheral tissues. It appears to be one of the most
      promising therapeutic targets for treatment of diabetes mellitus type 2.
      Surprisingly, very little is known about the cellular mechanisms that regulate
      receptor function in living cells. One of the approaches how to study receptor
      dynamics is by using tagged fluorescent proteins. In this study, YFP-tagged GLP-1
      (YFP-GLP-1) receptor and CFP-tagged GLP-1 (CFP-GLP-1) receptor for visualizing
      protein-protein interaction in living cells were constructed and localized in CHO
      cells. Cells expressing YFP-GLP-1 and CFP-GLP-1 receptor showed characteristic
      GLP-1 mediated increase in cAMP, similar to cells expressing a wild type GLP-1
      receptor. This means that both types of receptors are functional and localized in
      plasma membrane.

PMID- 19757165
TI  - Identification of a new QTL for Fusarium head blight resistance in the wheat
      genotype "Wang shui-bai".
AB  - Fusarium head blight (FHB) is one of the most devastating wheat diseases, causing
      both yield loss and quality reduction. To detect quantitative trait loci (QTL)
      responsible for FHB resistance, plants of the F 2:3 population derived from a
      'Wangshui-bai' x 'Sy95-7' cross were artificially inoculated. Of 396 simple
      sequence repeats (SSRs), 125 amplified fragment length polymorphisms were used
      for FHB resistance QTL analysis. Five QTLs for FHB resistance were detected on
      chromosomes 3B, 6B, 7A, 1B and 2D. The effect of the QTL located on chromosome 3B
      on phenotypic variation was 31.69%, while that of the QTL found on 2D was the
      smallest and only accounted for 4.98% of the variation. The resistance alleles
      originated from 'Wangshibai' and association of the QTLs using these SSR markers
      may facilitate marker-assisted selection to improve FHB resistance in the wheat
      breeding programs of southwest China.

PMID- 19757166
TI  - Role of the Yes and Csk tyrosine kinases in the development of a pathological
      state in the human retina.
AB  - Amplification and a cloning of fragments of genes of human retina tyrosine
      kinases, the nucleotide sequences of which feature a high homology to the gene
      families of the Yes and Csk tyrosine kinases, and a cloning of the complete
      coding sequence of the cDNA of the Csk tyrosine kinase gene of the human
      lymphocytes have been carried out. It has been established that this sequence
      contains 1,624 bp and encodes a protein that, with a 99% homology, corresponds to
      the human tyrosine kinase. A comparative analysis of the nucleotide sequences of
      the full-size cDNA of the Csk tyrosine kinase of the lymphocytes of healthy
      donors and of patients with an eye choroidal melanoma has shown that a risk of
      development of an eye choroidal melanoma can be estimated by the frequency of
      occurrence of a mutant allele in the 10th exon.

PMID- 19757167
TI  - Maggot excretions/secretions induces human microvascular endothelial cell
      migration through AKT1.
AB  - Maggot therapy is a simple and highly successful method for healing of infected
      and necrotic wounds. The increasing evidences indicate that Maggot
      excretions/secretions (ES) plays important roles in the wounds healing process.
      But the precise molecular mechanisms remain undefined. Herein, we investigated if
      ES induced cell migration during wound healing process using microvascular
      endothelial cells (HMEC-1) as model, and this effect was associated with the
      activation of AKT1 and ERK1/2. Wound healing and transwell migration assays were
      performed to study the effects of ES on HMEC-1 cell migration. Our data showed
      that ES significantly induced HMEC-1 cell migration in both wound healing and
      transwell assays, and time-dependently (P < 0.05) activated AKT1, but not ERK1/2.
      Moreover LY294002 (a PI3K inhibitor) partially attenuated (P < 0.05) ES-induced
      cell migration in wound healing assay while completely inhibited (P < 0.05) ES
      induced AKT1 activation. These findings demonstrate that ES directly induces HMEC
      1 cell migration and this event is partially mediated by the activation of AKT1.

PMID- 19757168
TI  - Molecular characterization, chromosomal location, alternative splicing and
      polymorphism of porcine GFAT1 gene.
AB  - Glutamine: fructose-6-phosphate amidotransferase (GFAT) is the rate-limiting
      enzyme of the hexosamine synthesis pathway, which plays important roles in
      insulin resistance and glucose toxicity. GFAT1 is one of the two isoenzymes of
      GFAT. In the present study, we cloned cDNA sequence of the porcine GFAT1 gene and
      identified a GFAT1 splice variant (designed GFAT1-L) that contains a 54 bp
      insertion within the coding region. Nested RT-PCR revealed that GFAT1 was
      ubiquitously expressed in all tested tissues, but GFAT1-L was only expressed in
      skeletal muscle and heart, not in liver, spleen, lung, kidney, small intestine,
      stomach and fat tissue, suggested that GFAT1-L was selectively expressed in
      striate muscle in pig. Using both the somatic cell hybrid panel and radiation
      hybrid panel, the GFAT1 gene was mapped to porcine chromosome 3q21-q27, in which
      several significant QTLs for carcass traits were found. Among the SNPs we found
      in porcine GFAT1 gene, only the g. 101A>G polymorphism which located in intron 8
      was polymorphic in two pig populations we investigated in the study. Association
      analyses revealed that the g. 101A>G polymorphism has a significant effect on
      lean meat percentage (P < 0.05), corrected backfat thickness (P < 0.05) and
      backfat at the rump (P < 0.05).

PMID- 19757169
TI  - The influence of ADAR1's regulation on lymphocyte cell function during rejection.
AB  - The RNA editing adenosine deaminase gene (ADAR1) expression is wide-spread in
      lymphocytes. We explore the mechanism of ADAR1 regulation on the function of T
      primary lymphocytes when rejection occurs by knock-down the expression of ADAR1
      in mouse T primary lymphocytes in mixed lymphocyte cultures. The changes of cell
      proliferation, the expression of ADAR1 and the cell cycle related genes cyclin D1
      and A1, cell cycle and apoptosis analysis and mouse gene expression profiles was
      evaluated. We found that treatment with ADAR1-specific siRNA inhibited allogenic
      antigen stimulated T cell proliferation, arrested T cell cycle at G(0)/G(1)
      phases and promoted T cell apoptosis, which was associated with down-regulation
      of some related key genes transcription. These findings suggest that ADAR1 is
      essential for the maintenance of function of T lymphocytes during acute
      rejection. The mechanism underlying ADAR1's action might include editing of a
      currently unknown substrate and interacting with other proteins.

PMID- 19757170
TI  - Validation of endogenous reference genes for insecticide-induced and
      developmental expression profiling of Liposcelis bostsrychophila (Psocoptera:
      Liposcelididae).
AB  - Four housekeeping genes named Lbbeta-Actin1, Lbbeta-Actin2, Lbalpha-Tubulin, and
      LbGapdh were cloned from Liposcelis bostrychophila using the combined techniques
      of reverse transcriptase-PCR (RT-PCR) with rapid amplification of cDNA ends
      (RACE). The GenBank accession numbers were FJ196622, FJ447483, FJ595242, and
      FJ595241, respectively. The full-length cDNA of Lbbeta-Actin1 was a 1,772 bp
      sequence with an open reading frame (ORF) encoded 376 amino acids, while Lbbeta
      Actin2 was 1,350 bp in length containing an ORF encoded 376 amino acids.
      Furthermore, the 1,565 bp cDNA of Lbalpha-Tubulin had an ORF of 1,350 bp encoding
      450 amino acids. And LbGapdh possessed an ORF of 333 amino acids. Sequences
      analysis and phylogenetic trees generated from the nucleotide sequences of their
      coding regions revealed a relationship that was closer to other insects than to
      mammals. The four genes together with 18S rRNA were quantified for transcription
      stability in L. bostrychophila, and the geNorm software ranked from the most to
      least were Lbbeta-Actin1 > LbGapdh > Lbalpha-Tubulin > Lbbeta-Actin2 > Lb18S rRNA
      for deltamethrin induction, while ranked Lbbeta-Actin1 > Lbalpha-Tubulin > Lbbeta
      Actin2 > LbGapdh > Lb18S rRNA for the different developmental stages.

PMID- 19757171
TI  - Codon optimization of cry1Ab gene for hyper expression in plant organelles.
AB  - With the advent of genetic manipulation techniques, it has become possible to
      clone and insert gene into the genome of crop plants to confer resistance to
      insects and pests. Resistance to insects has been demonstrating in transgenic
      plants either by triggering defense system of plants or by expressing
      heterologous cry genes for delta-endotoxins from Bacillus thuringiensis. In the
      present study, synthetic cry1Ab gene was developed with optimized chloroplast
      preferred codons and is expressed in tobacco plastid genome called plastome,
      following chloroplast transformation strategy, which is environment friendly
      technique to minimize out-crossing of transgenes to related weeds and crops. In
      addition, due to high polyploidy of plastid genome transformation of chloroplast
      permits the introduction of thousands of copies of foreign genes per plant cell,
      leading to extraordinarily high levels of foreign protein expression. The
      chloroplast transformation technology aims to insert stably into the plastome
      through homologous recombination into pre-decided position. To characterize the
      synthetic cry1Ab gene, chloroplast transformation vectors were developed and
      bombarded to the leaf cells of tobacco plants maintained under aseptic
      conditions. After bombardment, the drug resistant shoots were selected and
      regenerated on drug containing regeneration medium. Homoplasmic shoots were
      recovered after successive rounds of selection and regeneration. Proliferated
      plants were subjected to genomic DNA analysis by using polymerase chain reaction
      (PCR) technique where cry1Ab gene-specific primers were used. PCR positive plants
      were subjected to protein analysis, and functionally expressed proteins were
      detected using Immuno-Strips specific for cry1Ab/Ac gene products. Transgenic
      plants carrying cry1Ab gene were found expressing Bt toxins confirming that
      engineered gene could be expressed in other plants as well.

PMID- 19757172
TI  - The growth-inhibition effect of tamoxifen in the combination chemotherapeutics on
      the human cholangiocarcinoma cell line QBC939.
AB  - In the individual application of adriamycin, mitomycin, vindesine and their
      combined application with tamoxifen for the pre-treatment of the human
      cholangiocarcinoma cell line QBC939, QBC939 was determined by MTT assay to
      investigate the inhibitive effect and its initial mechanism of TAM on cell
      growth. Growth cycle and apoptosis of each group were determined by flow
      cytometry. Concentration of ADM in QBC939 was detected by flow cytometry. The
      levels of their P-glycoprotein were detected by immunohistochemistry. The mRNA
      and protein levels of apoptotic-associated genes Bcl-2 and Bax were determined by
      western blot and real-time PCR. The inhibitive rates of adriamycin, mitomycin,
      vindesine to QBC939 and the apoptosis rates of QBC939 were enhanced after the pre
      treatment of tamoxifen. Influence of tamoxifen in their growth cycle was not so
      obvious except vindesine group because of the increasing cell numbers of G (2)/M
      phase in which cells may be blocked. The contents of adriamycin in cells rose
      after the pre-treatment of tamoxifen. Expression level of the multi-drug
      resistant protein on cell surface was shown as (+). Furthermore, real-time PCR
      and Western blot analysis revealed an upregulation of Bcl-2 and a downregulation
      of Bax in QBC939 after the pre-treatment of tamoxifen. Therefore, tamoxifen may
      have the ability to enhance the relative sensitivity of QBC939 to
      chemotherapeutics.

PMID- 19757173
TI  - Association of interleukin 1beta gene (+3953) polymorphism and severity of
      endometriosis in Turkish women.
AB  - Endometriosis is regarded as a complex trait, in which genetic and environmental
      factors contribute to the disease phenotype. We investigated whether the
      interleukin (IL) 1beta (+3953) polymorphism is associated with the severity of
      endometriosis. Diagnosis of endometriosis was made on the basis of laparoscopic
      findings. Stage of endometriosis was determined according to the Revised American
      Fertility Society classification. 118 women were enrolled in the study. 78 women
      did not have endometriosis, 6 women had stage I, 3 had stage II, 13 had stage III
      and 18 had stage IV endometriosis. Polymerase Chain Reaction (PCR), Restriction
      Fragment Length Polymorphism (RFLP), and agarose gel electrophoresis techniques
      were used to determine the IL 1beta (+3953) genotype. Frequencies of the IL-1beta
      (+3953) genotypes in the control group were: CC, 0.397; TT, 0.115; CT, 0.487.
      Frequencies of the IL-1beta (+3953) genotypes in cases were: CC, 0.375; TT,
      0.225; CT, 0.400. We found a 2.22 fold increase in TT genotype in the
      endometriosis group. However, the difference was not statistically significant (P
      > 0.05). We also observed an increase in the frequency of IL-1beta (+3953) T
      allele in the endometriosis group. However, the difference was not statistically
      significant. We also investigated the association between IL-1beta (+3953)
      polymorphism and the severity of endometriosis. The frequencies of CC+CT
      genotypes in stage I, III and IV endometriosis patients were 83.3, 84/6 and
      72.2%, respectively; and TT genotypes were 16.7, 15.4 and 27.8%, respectively. We
      observed a statistically insignificant increase in TT genotype in stage IV
      endometriosis (P > 0.05). We suggest that IL-1beta (+3953) polymorphism is not
      associated with endometriosis in Turkish women.

PMID- 19757174
TI  - Differential display reveals a novel pig gene, PRPF3, which is differentially
      expressed in Large White versus Wujin skeletal muscle tissues.
AB  - The mRNA differential display technique was performed to investigate gene
      expression differences in the longissimus dorsi muscle from Wujin and Large White
      pigs. A fragment of one differentially expressed gene was isolated and sequenced.
      A complete cDNA sequence of the gene was obtained using the rapid amplification
      of cDNA ends method. The open reading frame of this gene encodes a protein of 683
      amino acids, which is homologous with the PRP3 pre-mRNA processing factor 3
      (PRPF3) of five species: bovine (99%), human (99%), sumatran orangutan (99%),
      mouse (99%) and chicken (94%). This newly identified gene was respectively
      defined as the swine PRPF3 gene. This gene is structured in 15 exons and 14
      introns as revealed by computer-assisted analysis. The phylogenetic tree analysis
      revealed that the swine PRPF3 gene has a closer genetic relationship with the
      PRPF3 gene of sumatran orangutan.

PMID- 19757175
TI  - The role of lysophosphatidic acid receptors in phenotypic modulation of vascular
      smooth muscle cells.
AB  - Lysophosphatidic acid (LPA) is a bioactive lipid with diverse physiological
      effects via activation of G protein-coupled receptors (GPCRs). It has been
      implicated as a specific dedifferentiation factors that can promote phenotypic
      modulation of cultured vascular smooth muscle cells (VSMCs) which is critically
      involved in various vascular disease. However, the role of LPA receptors and
      details of their signaling in LPA induced phenotypic modulation are largely
      unexplored. In this study we detect the expression of LPA1 and LPA3 in rat aortic
      smooth muscle cells (RASMCs). LPA promoted RASMCs phenotypic modulation in a dose
      dependent manner and coordinated induced the phosphorylation of p38 mitogen
      activated protein kinase (p38MAPK) and extracellular signal-regulated kinase
      (ERK). LPA-induced cell phenotypic modulation was significantly inhibited by
      specific LPA1/LPA3-receptor antagonist dioctyl-glycerol pyrophosphate (DGPP8:0)
      at concentration, but this inhibitive effect was lost when the antagonist was
      coadministered with a highly selective LPA3 agonist,1-oleoyl-2-Omethyl-rac
      glycero-phosphothionate (OMPT). In addition, pertussis toxin (PTX), a Gi protein
      inhibitor had little affect on the LPA-induced phenotypic modulation in RASMC.
      These data suggest that LPA-induced phenotypic modulation is mediated through the
      PTX-insensitive G-protein(s), possibly Gq-coupled LPA3 receptor.

PMID- 19757176
TI  - cDNA sequence and tissues expression analysis of lipoprotein lipase from common
      carp (Cyprinus carpio Var. Jian).
AB  - A full-length cDNA coding lipoprotein lipase (LPL) was cloned from liver of adult
      common carp (Cyprinus carpio Var. Jian) by RT-PCR and rapid amplification of cDNA
      ends (RACE) approaches. The cDNA obtained was 2,411 bp long with a 1,524 bp open
      reading frame (ORF) encoding 507 amino acids. This amino acid sequence contains
      two structural regions: N-terminus (24-354 residues) and C-terminus (355-507
      residues). Before N-terminus, 1-23 residues is signal peptide, 6-23 residues is
      transmembrance helix. At N-terminus, some conversed functional sites were found,
      including two N-linked glycosylation sites Asn(41) and Asn(88); one catalytic
      triad Ser(174), Asp(198) and His(283); one conserved heparin-binding site
      Arg(321) to Arg(324) (RKNR); eight cysteines residues Cys(69) and Cys(82),
      Cys(258) and Cys(281), Cys(306) and Cys(325), Cys(317) and Cys(320) which are
      involved in four disulfide bridges; one polypeptide "lid" that participates in
      substrate specificity. At C-terminus, Asn(401) is another N-linked glycosylation
      site, and Trp(434) and Trp(435) (WW) is lipid-binding site. The amino acid
      sequence has a high similarity, and shows similar structural features to LPL of
      other species. Tissue distribution of LPL mRNA in liver, head kidney, mesenteric
      adipose tissue, heart and white muscle of common carp was analyzed by semi
      quantitative RT-PCR method using beta-actin gene as internal control. The result
      showed that the expressions of LPL mRNA were detected in all examined tissues of
      common carp. The expression levels of LPL in the mesenteric adipose tissue was
      highest among these tissues, following in liver and head kidney, and the lowest
      expression was found in heart and white muscle.

PMID- 19757177
TI  - Differential expression of a novel gene BRE (TNFRSF1A modulator/BRCC45) in
      response to stress and biological signals.
AB  - Stress-responsive genes play critical roles in many biological functions that
      includes apoptosis, survival, differentiation and regeneration. We have
      identified a novel stress-responsive gene called BRE which interacts with TNF
      receptor-1 and blocks the apoptotic effect of TNF-alpha. BRE enhances tumor
      growth in vivo and is up-regulated in hepatocellular and esophageal carcinomas.
      BRE also regulates the ubiquitination of the DNA repair complex BRCC, and the
      synthesis of steroid hormones. Here, we examined BRE-mRNA in cells after
      treatments with UV and ionizing radiation (IR). UV and IR treatment alone
      suppressed BRE-mRNA levels by more than 90% at 24 h, while hydroxyurea,
      fluorodeoxyuridine, aphidicolin, known inhibitors of S-phase DNA synthesis, had
      no significant effect. BRE protein expression was unaltered in cells treated with
      TNF-alpha, Interleukin-1 and Dexamethasone, while a threefold increase was
      observed following chorionic gonadotropin exposure. Although BRE plays a
      regulatory role in many different pathways, yet its expression is apparently
      under very stringent control.

PMID- 19757178
TI  - Phylogenetic analysis of 16S rRNA gene sequences reveals rumen bacterial
      diversity in Yaks (Bos grunniens).
AB  - Six matured male Yaks (Bos grunniens) with a mean live weight of 450 +/- 23 kg
      (mean +/- SD), were housed indoors in metabolism cages and fed pelleted lucerne
      (Medicago sativum). After an adjustment period of 24 days of feeding the diet,
      samples of rumen content were obtained for analysis of the bacteria in the
      liquor. The diversity of rumen bacteria was investigated by constructing a 16S
      rRNA gene clone library using the general bacterial primers F27 and R1492. A
      total of 130 clones, comprising nearly full length sequences (approx. 1.5 kb)
      were sequenced and submitted to BLAST and phylogenetic analysis. Using the
      criterion that similarity of 97% or greater with the sequences of cultivated
      bacteria, 16 clones were identified as Butyrivibrio fibrisolvens,
      Pseudobutyrivibrio ruminis, Ruminococcus flavefaciens, Succiniclasticum ruminis,
      Selenomonas ruminantium and Prevotella ruminicola, respectively. A further 10
      clones shared similarity ranging from 90 to 97% with cultivated bacteria but the
      similarity in sequences for the remaining 104 clones were less than 90% of those
      of cultivated bacteria. Using a phylogenetic analysis it was found that the
      majority of the clones identified (63.8%) were located in the Low G + C
      Subdivision, with most of the remainder (35.4% of clones) located in the
      Cytophaga-Flexibacter-Bacteroides phylum and one clone (0.8%) was identified as a
      Proteobacteria. It was apparent that Yaks have a large and diverse range of
      bacteria in the rumen content which differ from those of cattle and other
      ruminants.

PMID- 19757179
TI  - beta-Ionone-induced apoptosis in human osteosarcoma (U2os) cells occurs via a p53
      dependent signaling pathway.
AB  - beta-Ionone is a constituent of vegetables and fruits, and can induce apoptosis
      in some types of malignant cells. However, the mechanism of apoptosis in
      osteosarcoma (U2os) cells is currently unclear. In this study, we determined
      whether beta-ionone can induce apoptosis in U2os cells in vitro and which signal
      pathway(s) is involved. We found that beta-ionone inhibited cell proliferation in
      U2os cells in a concentration- and time-dependent manner and caused cell cycle
      arrest at the G1-S phase. TUNEL assay, DNA ladder and assessment of Caspase 3
      activity showed that apoptosis was the determinant in the effects of beta-ionone.
      Furthermore, Expression of the p53 protein increased in a concentration-dependent
      and time-dependent manner according to immunocytochemistry and immunoblotting
      after beta-ionone treatment. In addition, beta-ionone upregulated Bax protein and
      downregulated Bcl2 protein which led to Bax translocation and cytochrome c
      release, subsequently activated Caspase 3, thus resulting in apoptosis. In
      summary, these data suggested that beta-ionone induced apoptosis in a
      concentration-dependent manner in U2os cells via a p53-dependent mitochondrial
      pathway.

PMID- 19757180
TI  - Differential expression of TRPC channels in the left ventricle of spontaneously
      hypertensive rats.
AB  - This study was designed to identify the differential expression of the canonical
      transient receptor potential (TRPC) channels in the left ventricle of
      spontaneously hypertensive rats (SHR). Echocardiography studies were performed to
      compare the left ventricular function in SHR vs. Wistar-Kyoto rats (WKY), and the
      mRNA level of the TRPC channels was determined by quantitative real-time RT-PCR
      (qRT-PCR). Western blots were performed to examine whether the mRNA expression
      corresponded with the protein expression. Compared with the WKY, the mRNA
      expression of TRPC4 and TRPC5 was significantly increased in the 10-week-old SHR
      (P = 0.032 for TRPC4 and P = 0.043 for TRPC5), so did the TRPC4/5 protein
      content. The midwall fractional shortening (mFS) of SHR was lower than WKY (P =
      0.016). Furthermore, increased expression of TRPC4/5 was correlated with both
      increased blood pressure and decreased mFS. These findings suggest that TRPC4 and
      5 seem to be the main subtypes expressed in the heart of the SHR at the beginning
      period of hypertension. Theses channels may participate in the development of
      left ventricular systolic dysfunction.

PMID- 19757181
TI  - Characterization of gene expression of QM from Caragana jubata, a plant species
      that grows under extreme cold.
AB  - Caragana [Caragana jubata (Pall.) Poir] is a temperate plant that thrives well
      under extremes of cold in high altitude of Himalaya and hence the plant is
      expected to be a source of genes that might play an important role in tolerance
      to low temperature (LT). In order to identify LT inducible gene(s), differential
      display of mRNA (DD) was performed using the apical buds growing under snow as
      well as growing in the near vicinity without snow, and a LT inducible QM gene
      (CjQM) homologue was identified. Realizing the importance of QM gene (which
      encodes human Wilms' tumor suppressor QM protein) in aggregation of 40 and 60S
      ribosomal subunit and that not much has been reported on this gene in plant
      systems in relation to its relationship with LT, full length cDNA of CjQM was
      cloned through rapid amplification of cDNA ends. The gene (977 bp), encoded by
      small gene family, had an open reading frame of 651 bp and was found to be
      intronless. The gene exhibited up-regulation within 20 min of exposure to LT and
      abscisic acid (ABA), but no significant change in gene expression was observed in
      response to drought stress (DS), salicylic acid (SA) and methyl jasmonate (MJ)
      application. Up-regulation of CjQM was obtained in the tissues growing in situ
      under snow. Non-responsiveness of CjQM towards DS, SA and MJ, but up-regulation
      in response to LT and ABA suggested a specific regulation of the gene in Caragana
      under varied cues.

PMID- 19757182
TI  - RNA interference: a potent technology in studying and modulating of dendritic
      cells, and potential in clinical therapy.
AB  - RNA interference (RNAi) is a natural process by which small interfering RNA
      duplex directs sequencespecific post-transcriptional silencing of homologous
      genes by binding to its complementary mRNA and triggering its elimination. The
      history of RNAi has only about two decades, however, further studies have
      revealed that it is a potent method of gene silencing that has developed rapidly
      over the past few years as a result of its extensive importance in the study of
      genetics, molecular biology and physiology. RNAi technology has also recently
      yielded significant insight into dendritic cells (DCs) by helping to elucidate
      numerous mechanisms that regulate the development, activation and function of
      cells that mediate immunity. In addition, because of its ability to suppress gene
      expression effectively, this technique may be used to regulate the immune
      response for clinical purposes. As the key antigen presenting cells, DCs play a
      crucial part in the start of an immune response and in the enhancement and
      regulation of cell mediated immune reactions. The current studies indicated that
      targeting DCs with RNAi is a novel and effective therapeutic method for the
      fundamental research, and displayed great potential in clinical treatment.

PMID- 19757183
TI  - Effects of cyclic strain on rat tail tenocytes.
AB  - Cyclical mechanical strain is considered an important component in flexor tendon
      cell activation to prevent adhesions and enhance the healing process after tissue
      injury or surgery, but the biochemical events associated with this remain
      unclear. To address this, we examined the effects of cyclic tension on the
      expression of hyaluronic acid, an important lubricant and signal transducer in
      tendon, on its receptor (CD44), and on total glycosaminoglycan content in rat
      tail derived tendon fibroblasts in vitro. Tenocytes were plated on fibronectin
      coated silastic membranes and the cultures were held static or subjected to
      vacuum induced deformation for a period of 5 min once every 8 h as a model of
      cyclic mechanical stress. After 24 h medium and cell layers were collected for
      analyses by product specific ELISA, Western blot, and colorimetric dye-binding
      assays. Strained tenocytes produced a nearly two-fold increase in hyaluronic acid
      and a greater than 60% increase in CD44, but had an insignificant effect on total
      glycosaminoglycan content. Our results predict that high levels of strain may
      therefore rapidly enhance the expression of hyaluronic acid and cause, albeit
      still unresolved, downstream effects on CD44 activation, to influence tendon cell
      activity and enhance the process of tendon repair.

PMID- 19757184
TI  - Molecular cloning and expression characterization of translationally controlled
      tumor protein in silkworm pupae.
AB  - A Bombyx mori (B. mori) cDNA was isolated from silkworm pupae cDNA library
      encoding a homologue of translationally controlled tumor protein (BmTCTPk).
      BmTCTPk was expressed in E. coli; SDS-PAGE and Western blot showed the molecular
      weight of recombinant and native BmTCTPk is approximately 28 and 25 kDa,
      respectively; they are larger than the theoretical molecular weight.
      Immunohistochemical studies showed that BmTCTPk is uniformly distributed
      throughout the cytoplasm of BmN cells. In silkworm pupae, BmTCTPk is expressed in
      the midgut wall, the midgut cavity, and some fat body tissues lying between the
      midgut wall and body wall. Western blot and ELISAs performed on total protein
      extracts isolated from silkworm pupae at different development stages showed
      that, although BmTCTPk is expressed during all pupae stages, its expression level
      increases dramatically during late pupae stages, suggesting that BmTCTPk may play
      an important role during the developmental transition from pupa to imago.

PMID- 19757185
TI  - Role of dephosphorylation of FOXO1 on apoptosis induced by wortmannin for non
      Hodgkin's lymphoma cells.
AB  - The aim of this study was to ascertain the relationship between the
      phosphorylation of FOXO1 and the apoptosis and the proliferation of lymphoma
      cells so as to further clarify the cellular biology and pathogenesis of the
      disease. The lymphoma cells Namalwa and Jurkat were treated with PI3K inhibitor
      wortmannin or etoposide alone or wortmannin plus etoposide with different
      schedule. The inhibition rates of lymphoma cell growth were examined by XTT
      assay. Apoptosis were detected by flow cytometry. The expression of p-Akt, p
      FOXO1, FOXO1, bim were determined by western blot analysis. Wortmannin induced
      apoptosis of Jurkat cells and Namalwa cells and inhibited their survival
      effectively. The rate of growth inhibition and apoptosis of lymphoma cells
      induced by wortmannin plus etoposide were higher than those induced by etoposide
      alone. After treated with wortmannin, phosphorylation of FOXO1 remarkably reduced
      and bim increased. The dephosphorylation of FOXO1 inhibited proliferation of
      Jurkat cells and Namalwa cells, promoted their apoptosis and sensitized Non
      Hodgkin lymphoma cells to etoposide. Bim activated by FOXO1 promoted cells
      apoptosis.

PMID- 19757186
TI  - A comparative analysis of the complete mitochondrial genome of the Eurasian otter
      Lutra lutra (Carnivora; Mustelidae).
AB  - Otter populations are declining throughout the world and most otter species are
      considered endangered. Molecular methods are suitable tools for population
      genetic research on endangered species. In the present study, we analyzed the
      complete mitochondrial genome (mitogenome) sequence of the Eurasian otter Lutra
      lutra. The mitochondrial DNA sequence of the Eurasian otter is 16,505 bp in
      length and consists of 13 protein-coding genes, 22 tRNAs, 2 rRNAs, and a control
      region (CR). The CR sequence of otters from Europe and Asia showed nearly
      identical numbers and nucleotide sequences of minisatellites. Phylogenetic
      analysis of Mustelidae mitogenomes, including individual genes, revealed that
      Lutrinae and Mustelinae form a clade, and that L. lutra and Enhydra lutris are
      sister taxa within the Lutrinae. Phylogenetic analyses revealed that of the 13
      mitochondrial protein-coding genes, ND5 is the most reliable marker for analysis
      of phylogenetic relationships within the Mustelidae.

PMID- 19757187
TI  - Factors associated with health-related quality of life after successful kidney
      transplantation: a population-based study.
AB  - INTRODUCTION: Kidney transplantation improves the quality of life of end-stage
      renal disease patients. The quality of life benefits, however, pertain to
      patients on average, not to all transplant recipients. The aim of this study was
      to identify factors associated with health-related quality of life after kidney
      transplantation. METHODS: Population-based study with a cross-sectional design
      was carried out and quality of life was assessed by SF-36 Health Survey Version
      1. A multivariate linear regression model was constructed with sociodemographic,
      clinical and laboratory data as independent variables. RESULTS: Two hundred and
      seventy-two kidney recipients with a functioning graft were analyzed.
      Hypertension, diabetes, higher serum creatinine and lower hematocrit were
      independently and significantly associated with lower scores for the SF-36
      oblique physical component summary (PCSc). The final regression model explained
      11% of the PCSc variance. The scores of oblique mental component summary (MCSc)
      were worse for females, patients with a lower income, unemployed and patients
      with a higher serum creatinine. The regression model explained 9% of the MCSc
      variance. CONCLUSIONS: Among the studied variables, comorbidity and graft
      function were the main factors associated with the PCSc, and sociodemographic
      variables and graft function were the main determinants of MCSc. Despite
      comprehensive, the final regression models explained only a little part of the
      heath-related quality of life variance. Additional factors, such as personal,
      environmental and clinical ones might influence quality of life perceived by the
      patients after kidney transplantation.

PMID- 19757188
TI  - Determinants of global quality of life before and after major cancer surgery: an
      exploratory study.
AB  - OBJECTIVE: To explore whether determinants of global quality of life (QOL) change
      before and after major cancer surgery. METHODS: Consecutive patients (n = 145)
      undergoing surgery for upper gastrointestinal cancer were prospectively studied
      and asked to complete the EORTC QLQ-C30 before and after 6 months. Excluded were
      patients found to be inoperable (n = 12) and those with missing second
      questionnaires (because of death n = 20, poor health (n = 10), administrative
      failure (n = 7) or patient refusal (n = 4)). Multivariable linear regression
      models investigated associations between global QOL and other scales and items of
      QOL adjusting for clinical variables. RESULTS: Some 87 patients completed both
      questionnaires. Before surgery the main predictors of global QOL were physical
      and emotional function, with adjusted increases in global QOL of 0.55 (95% CI
      0.26-0.84; P < 0.001) and 0.30 (95% CI 0.14-0.45; P < 0.001) per unit increase of
      physical and emotional function, respectively. Six months after surgery, however,
      fatigue and dyspnea most strongly predicted global QOL, with adjusted differences
      in global QOL of -0.24 (95% CI -0.44 to -0.04; P = 0.02) per unit increase of
      fatigue and -6.28 (95% CI -12.64 to 0.07; P = 0.05) for those experiencing any
      symptoms of dyspnea. CONCLUSION: Further work is needed to test these findings,
      but the results suggest that the global QOL scale in the QLQ-C30 is difficult to
      interpret and it should be considered within the context of other clinical and
      patient reported outcomes.

PMID- 19757189
TI  - Coherent activation of a synthetic mammalian gene network.
AB  - A quantitative analysis of naturally-occurring regulatory networks, especially
      those present in mammalian cells, is difficult due to their high complexity. Much
      simpler gene networks can be engineered in model organisms and analyzed as
      isolated regulatory modules. Recently, several synthetic networks have been
      constructed in mammalian systems. However, most of these engineered mammalian
      networks have been characterized using steady-state population level
      measurements. Here, we use an integrated experimental-computational approach to
      analyze the dynamical response of a synthetic positive feedback network in
      individual mammalian cells. We observe a switch-like activation of the network
      with variable delay times in individual cells. In agreement with a stochastic
      model of the network, we find that increasing the strength of the positive
      feedback results in a decrease in the mean delay time and a more coherent
      activation of individual cells. Our results are important for gaining insight
      into biological processes which rely on positive feedback regulation. ELECTRONIC
      SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11693
      009-9044-5) contains supplementary material, which is available to authorized
      users.

PMID- 19757190
TI  - Between same-sex marriages and the Large Hadron Collider: making sense of the
      precautionary principle.
AB  - The Precautionary Principle is a guide to coping with scientific uncertainties in
      the assessment and management of risks. In recent years, it has moved to the
      forefront of debates in policy and applied ethics, becoming a key normative tool
      in policy discussions in such diverse areas as medical and scientific research,
      health and safety regulation, environmental regulation, product development,
      international trade, and even judicial review. The principle has attracted
      critics who claim that it is fundamentally incoherent, too vague to guide policy,
      and makes demands that are logically and scientifically impossible. In this paper
      we will answer these criticisms by formulating guidelines for its application
      that ensure its coherence as a useful normative guide in applied and policy
      ethics debates. We will also provide analyses of cases that demonstrate how our
      version of the principle functions in practice.

PMID- 19757191
TI  - Nucleolin/C23 is a negative regulator of hydrogen peroxide-induced apoptosis in
      HUVECs.
AB  - Nucleolin plays important roles in chromatin structure, rDNA transcription, rRNA
      maturation, nucleocytoplasmic transport, and ribosome assembly. Although it has
      been shown to be anti-apoptotic, the underlying mechanisms remain unclear. In the
      current study, we first examined endogenous nucleolin expression in response to
      oxidative stress-induced apoptosis in human umbilical vascular endothelial cells
      (HUVECs). Flow cytometry and caspase activity assays showed that H(2)O(2)
      treatment caused apoptosis of the cells; reverse-transcription polymerase chain
      reaction and Western blotting revealed the downregulation of nucleolin expression
      and increased protein cleavage during this process. Overexpression of nucleolin
      protein by transfecting cells with the full-length nucleolin cDNA inhibited
      apoptosis, but nucleolin deficiency brought about by transfection with antisense
      oligonucleotide increased apoptosis of HUVECs. Concurrently, the expression of
      the apoptotic protein gene Bax was also downregulated following nucleolin
      overexpression. All these results indicate an important negative regulatory role
      for nucleolin in the apoptosis of endothelial cells, likely involving the Bax
      pathway.

PMID- 19757192
TI  - IFN gamma gene polymorphism may contribute to the susceptibility to CLL.
AB  - The pathogenesis of B-cell chronic lymphocytic leukemia (B-CLL) has been linked
      with the production and activity of certain growth factors. However a significant
      proportion of CLL patients display immune abnormalities suggestive of aberrant
      cytokine secretion and/or response. In contrast to B lymphocytes, T cells of B
      CLL patients characterise with the increased production of interferon-gamma (IFN
      gamma) and this cytokine has been indicated to prevent malignant cells from
      entering apoptosis including the slowly expanding population of CD5+ B cells that
      characterizes chronic lymphocytic leukemia. The aim of the present study was to
      assess whether functionally relevant interferon-gamma gene (IFNG) polymorphism
      (+847 A/T) contributes to the pathogenesis of B-CLL. In total 110 individuals was
      investigates, including 61 CLL patients and 50 healthy individuals. The presence
      of the IFNG AA genotype was found to be associated with susceptibility to CLL
      (23/61 vs. 7/50, p < 0.005, for patients and controls, respectively). This
      results suggest that individuals rather prone to the lower level of IFN-gamma
      production (associated with the presence of the A allele) appear to be more
      susceptible to this malignant disease.

PMID- 19757193
TI  - Neoadjuvant chemotherapy: does it have benefits for the surgeon in the treatment
      of advanced squamous cell cancer of the oral cavity?
AB  - The purpose of this clinicopathological study was to evaluate the effects and
      efficiency of combined neoadjuvant chemotherapy related to surgical margin. 100
      consecutively treated squamous cell cancer patients receiving a combined
      neoadjuvant therapy were selected (Bleomycin-Vincristin-Methotrexate (BVM) or BVM
      + Mitolactol or BVM + Cisplatin). After three courses of chemotherapy, the
      patients were operated on. The largest diameter of the primary tumors was
      compared before and after chemotherapy. In the surgical specimen, the involvement
      of surgical margin was assessed. The largest diameter before chemotherapy was: T2
      30%; T3 55%; T4A 15%. After chemotherapy, the rest tumor was assessed in the
      surgical specimen as: no rest 11%; <2 cm 57%; 2-4 cm 28%; 4-6 cm 4%. The no rest
      and <2 cm (optimal operability) tumor was observed in T2: 94%; in T3: 73%; in the
      T4A: 0%. Severe side effects (Grade III-IV) were not observed. There was a
      significant decrease in size (P < 0.0001). Of the 100 surgical specimens, 83% had
      clear-, 9% close- and 8% involved margins. From T4A, there was a 40% (6 patients)
      involved margin. Based on the significantly better size and operability of
      primary T2-3, the mild side effects and the high (83%) percentage of clear
      surgical margins, that is better than other (without preoperative chemotherapy)
      results, sought the use of chemotherapy is recommended before surgery. Due to the
      40% involved margin, we don't suggest surgery in T4A.

PMID- 19757194
TI  - Association between histological type of tumour growth and patient survival in t2
      t3 lymph node-negative rectal cancer treated with sphincter-preserving total
      mesorectal excision.
AB  - For rectal cancer patients without nodal metastases the identification of
      unfavourable factors can be helpful for the better selection for adjuvant therapy
      and multimodality treatment. The aim of this study was to evaluate the impact of
      clinico-histological parameters on prognosis in node-negative rectal cancer
      patients. One hundred and thirty-nine consecutive node negative rectal cancer
      patients with complete five-year follow-up were studied prospectively. All of
      them underwent curative anterior resection with total mesorectal excision
      technique. Seventy-eight patients with tumour penetration beyond the bowel wall
      received neo-adjuvant short-course radiation (25 Gy) followed by surgery within 1
      week and postoperative chemotherapy with 5-fluorouracil and folinic acid in six
      cycles or adjuvant radiochemotherapy: irradiation (50.4 Gy) combined with
      chemotherapy (as above). Cancer-specific survival was calculated according to the
      Kaplan-Meier method. Variables significant in univariate analysis by log-rank
      test (P < 0.05) entered the Cox proportional hazard model. Survival was decreased
      for males, older patients (>60 years) with extraperitoneal, poorly differentiated
      cancers, tumours with mucinous histology and with the absence of lymphocytic
      infiltration but with the lack of statistical importance. Prognosis was
      significantly improved for patients with T2 tumours versus T3 (P < 0.01) and with
      cancers with expanding growth comparing to diffusely infiltrating ones (P <
      0.01). In multivariate analysis these parameters significantly and independently
      influenced survival (P < 0.01 and P < 0.05, respectively). Diffusely infiltrating
      growth of tumour can reflect the more aggressive cancer behaviour and
      unfavourable course of disease despite the optimised local control. Apart from
      the extent of tumour penetration the type of invasive margin can be an additional
      parameter helpful for the optimal treatment planning and better patient selection
      for postoperative chemotherapy.

PMID- 19757195
TI  - Is predisposition for nephroblastoma linked to polymorphisms of the WTX gene?
AB  - Inactivation of Wilms tumor X (WTX) gene has been linked to the pathogenesis of a
      varying percentage of nephroblastomas. In contrast, germline mutations of WTX
      were identified to cause bone dysplasia, but not to induce the development of
      nephroblastomas. In our study we investigated whether tumor promotion of
      nephroblastoma by inactivation of WTX gene is linked to certain single nucleotide
      polymorphisms (SNPs). Therefore 8 SNPs-distributed over the whole length of the
      WTX gene-were investigated by high resolution melting curve analysis (HRMA) and
      sequencing of genomic DNA from nephroblastoma patients (NB) and controls. No
      difference was detected in the 8 SNPs investigated, which were distributed over
      the whole length of the gene. Additionally, sequence analysis of the coding part
      of the WTX gene of the tumor samples revealed no chromosomal aberration. Our
      study indicates, that inactivation of WTX appears to be a late event in
      tumorigenesis of nephroblastoma in a subgroup of nephroblastomas.

PMID- 19757196
TI  - The effect of LMWH (Nadroparin) on tumor progression.
AB  - Recent clinical studies on patients with malignancies, who were treated with UHF
      and LMWHs raised the possibility, that these agents may possess an inhibitory
      effect on tumor progression. Further studies supported that this effect is
      independent from the anticoagulant and antithrombotic action. In this
      retrospective study oncological patients with an increased risk for
      thromboembolism were choosen, who received prophylactic treatment with an LMWH
      (nadroparin) at least for 6 months. Comparing with the control group, in some
      subgroups (T3 and T4, as well as M1) the LMWH-treated patients showed a
      significantly increased survival.

PMID- 19757197
TI  - Proximal-type epithelioid sarcoma in the groin presenting as a diagnostic
      dilemma.
AB  - Epithelioid sarcoma is an uncommon soft-tissue sarcoma typically presenting as a
      subcutaneous or deep dermal mass in the distal extremities of young adults.
      Lately, a 'proximal' subtype has been described, which occurs in the pelvic and
      genital areas of somewhat older individuals and tends to behave more aggressively
      than the conventional subtype. The correct diagnosis of this subtype is
      essential, since this tumor can be easily mistaken for other malignant tumors
      that exhibit epithelioid morphology. We report a case of proximal-type
      epithelioid sarcoma that presented as an inguinal mass in a 47-year-old man.
      Histologically, the tumor consisted of diffuse sheets of epithelioid cells with
      scattered rhabdoid morphology. By immunohistochemistry, the neoplastic cells
      expressed cytokeratin, epithelial membrane antigen, vimentin, CD34, CD99 and
      showed complete loss of nuclear INI1 protein expression. Fluorescence in situ
      hybridization was considered borderline for 22q deletion. We present this case to
      emphasize the importance of diagnosing this uncommon tumor and the role of INI1
      immunohistochemistry in establishing the diagnosis.

PMID- 19757198
TI  - Expression and prognostic value of PRL-3 in human intrahepatic
      cholangiocarcinoma.
AB  - Phosphatase of regenerating liver (PRL)-3 is involved in the metastasis of
      various tumors, but the expression of PRL-3 and its possible role in primary
      intrahepatic cholangiocarcinoma (ICC) has not been reported yet. In this study,
      we assessed the expression levels of PRL-3 by immunohistochemistry in 102 primary
      ICC samples, 62 matched lymph node metastases (LNM) and 102 adjacent normal liver
      tissues. Then we investigated the relationship between PRL-3 expression and
      clinicopathologic factors. Survival analysis was performed to determine the
      prognostic significance of PRL-3 expression in ICC. Immunochemistry results
      suggested PRL-3 expression was negative or weak in non-neoplastic intrahepatic
      bile ducts of adjacent liver tissue. In primary lesion and LNM high PRL-3
      expression was frequently detected. Furthermore, the rate of high PRL-3
      expression in LNM was higher than that in primary lesion (80.6% vs. 47.1%, P <
      0.05). High expression of PRL-3 in primary tumors was significantly associated
      with TNM (P < 0.001), T stage (P < 0.001), vascular invasion (P = 0.002), and LNM
      (P < 0.001). Survival analysis results with Kaplan-Meier method and Cox
      proportional hazard model indicated high expression of PRL-3 was correlated with
      decreased overall survival and was an independent prognostic marker of overall
      survival. Thus, our results suggested high expression of PRL-3 was correlated
      with progression and metastasis of ICC and indicated negative prognostic impact.
      PRL-3 might serve as a novel prognostic marker for patients with ICC.

PMID- 19757199
TI  - Clusterin as a diagnostic and prognostic marker for transitional cell carcinoma
      of the bladder.
AB  - We investigated the feasibility of profiling and measuring the concentration of
      clusterin in urine and serum for individuals with transitional cell carcinoma
      (TCC) of the bladder and comparing it with nontumor controls. In addition, we
      analyzed the correlation of expression of clusterin in specimens of TCC to
      various clinicopathologic parameters and prognosis of bladder cancer. Blood and
      urine samples were used from 68 patients with TCC of the bladder and from 61
      patients with benign urological diseases. Enzyme-linked immunosorbent assays
      (ELISA) were performed for clusterin from serum and urine. Quantitation of
      clusterin mRNA was carried out in 68 bladder tumor specimens from radical
      cystectomy or transurethral resection and 26 normal bladder specimens from BPH
      patients by using RT-PCR method. Correlation for the expression of clusterin mRNA
      with clinicopathologic parameters was analyzed. Serum and urine clusterin was
      significantly higher in individuals with bladder cancer than control (p = 0.001).
      Sensitivity and specificity of serum and urine clusterin as a tumor marker for
      TCC of the bladder was found to be 80%, 91%, 87.1% and 96.7% respectively.
      Clusterin expression was significantly higher in TCC specimens than normal tissue
      specimens (P < 0.001). Expression of clusterin was significantly higher in
      patients with invasive TCC of the bladder than that in patients with superficial
      TCC and control (P < 0.001). Overexpression of clusterin mRNA was significantly
      associated with tumor recurrence and overall survival (p < 0.001). The recurrence
      free survival time of patients with overexpression of clusterin was significantly
      shorter than that of patients with weak expression of clusterin (9.8 months vs.
      35.2 months). Clusterin may be considered as a potential diagnostic and
      prognostic biomarker for bladder cancer using urine, serum and/or molecular
      biology techniques.

PMID- 19757200
TI  - Effect of liver steatosis on therapeutic response in chronic hepatitis C virus
      genotype 1 infected patients in hungary.
AB  - Hepatic steatosis seems a frequent histological alteration seen in chronic
      hepatitis C virus infected patients. There is still a lot to learn about the
      exact mechanism of effect of liver steatosis and its influence on the progression
      of liver diseases. Our study involved 96 chronic hepatitis C genotype 1 infected
      Hungarian patients who received pegylated interferon and ribavirin treatment for
      the first time. Degree of steatosis, viral and host factors influencing its
      development and its effect on the efficiency of antiviral treatment were
      determined. In 61 (64%) of patients the liver tissue showed varying degree of
      steatosis, which did not show relationship with level of alcohol consumption (p =
      0.5792), diabetes mellitus (p = 0.5925) or body mass index (p = 0.9685) in type 1
      chronic hepatitis C patients. Degree of steatosis and virus titer showed strong
      relationship (OR = 2.1). Significant relationship was also found between degree
      of hepatic steatosis and stage (p = 0.0119), as well as between therapeutic
      response to combined pegylated interferon + ribavirin treatment and steatosis (p
      = 0.0012). Our results demonstrated that steatosis has clinical significance in
      hepatitis C virus genotype 1 infected patients.

PMID- 19757201
TI  - Mitochondrial preservation in Celsior versus histidine buffer solution during
      cardiac ischemia and reperfusion.
AB  - Various stressful conditions such as ischemia in cold cardioplegic solutions and
      reperfusion occur during heart transplantation. Since ATP production is essential
      for the maintenance of contractile activity, mitochondrial function may be a
      mediator of ischemia and ischemia/reperfusion (I/R) injury. We aimed at testing
      the ability of two distinct cardioplegic solutions, Celsior (Cs) and Histidine
      Buffer (HBS), to protect rat heart mitochondria (HM) function during ischemia
      alone or ischemia followed by reperfusion. A standard Krebs-Henseleit solution
      (KH) was used as "negative" control. Male and Female Wistar rats were divided
      into control (Ctrl), reperfusion control (Ctrl_R), ischemia and I/R groups.
      Ischemia and I/R were divided into three subgroups depending on the cardioplegic
      solution used (Cs, HBS or KH) and subjected to 4-or 6-h ischemia alone or
      followed by reperfusion. HM respiration and transmembrane electric potential
      (Deltapsi) were measured with oxygen and TPP(+)-selective electrodes,
      respectively. Mitochondrial electron microscopy and detection of protein carbonyl
      groups content were also performed. After ischemic heart preservation,
      mitochondrial respiration and Deltapsi were not significantly affected except for
      the respiratory control ratio (RCR). After I/R, state 3 respiration, RCR and
      Deltapsi were decreased, especially in HM from male and for complex I substrates
      (CxI). HM preserved in HBS had less membrane disruption, segregation or
      disintegration. We conclude that (a) female HM were less sensitive to I/R, (b)
      CxI was particularly affected by I/R, (c) two cardioplegic solutions tested act
      in different mitochondrial targets preventing mitochondrial collapse.

PMID- 19757202
TI  - RAGE gene polymorphisms in patients with multiple sclerosis.
AB  - The pathogenesis of multiple sclerosis (MS), a devastating neuroinflammatory
      disorder of the central nervous system, has been presumed to involve the possible
      importance of the receptor for advanced glycation end products (RAGE). The aim of
      this study was to investigate the relevance of the genetic polymorphisms of RAGE
      in MS patients. A total of 168 patients with MS were enrolled; 136 healthy blood
      donors served as controls. The -374 T/ A, -479 T/C, and the G82S polymorphisms of
      RAGE were determined by restriction fragment length polymorphism (RFLP). There
      was a significant difference in RAGE -374 T/A genotype distribution between the
      controls and the MS patients. The AA homozygote variants were detected in 8% of
      the patients with MS, as compared with 19% of healthy controls (OR=2.75; 95%
      CI=1.319-5.733, p = 0.007). No differences were observed between the MS patients
      and the controls, concerning the frequencies of the -479 T/C and G82S genotypes
      of the RAGE. Our results revealed an association between the -374 T/A
      polymorphism of the RAGE promoter and MS. The genetic variant -374 AA (which has
      previously been shown to exert significant effects on transcriptional activity)
      can be considered a preventive factor as regards the occurrence of MS. Our
      findings support the view that RAGE plays a role in the development of MS.

PMID- 19757204
TI  - Down-regulation synaptic vesicle protein 2A in the anterior temporal neocortex of
      patients with intractable epilepsy.
AB  - Synaptic vesicle protein 2A (SV2A) involvement has been reported in the animal
      models of epilepsy. The aim of this study was to investigate the expression of
      SV2A in human intractable epilepsy (IE) brain tissue. Using immunohistochemistry,
      immunofluorescence, and Western blot, we detected SV2A expression in tissue
      samples from the anterior temporal neocortex of 33 patients who had been
      surgically treated for IE. We compared these tissues with nine histologically
      normal anterior temporal lobe samples from controls. SV2A immunoreactive staining
      was 0.1651+/-0.0564 in patient group and 0.2347+/-0.0187 in the control group
      (p<0.05) using immunohistochemistry, and this finding was consistently observed
      with Western blot analysis (0.1727 +/- 0.0471 versus 0.3976+/-0.0983, p<0.05).
      Immunofluorescence staining showed that SV2A was mainly accumulated in neurons.
      Our findings demonstrate that down-regulation of SV2A is present in patients with
      temporal lobe epilepsy.

PMID- 19757205
TI  - 2q37 as a susceptibility locus for idiopathic basal ganglia calcification (IBGC)
      in a large South Tyrolean family.
AB  - Familial idiopathic basal ganglia calcification (FIBGC) is an inherited
      neurodegenerative disorder characterized by the accumulation of calcium deposits
      in different brain regions, particularly in the basal ganglia. FIBGC usually
      follows an autosomal dominant pattern of inheritance. Despite the mapping to
      chromosome 14q of a susceptibility locus for IBGC (IBCG1) in one family, this
      locus has been excluded in several others, demonstrating genetic heterogeneity in
      this disorder. The etiology of this disorder thus remains largely unknown. Using
      a large extended multigenerational Italian family from South Tyrol with 17
      affected in a total of 56 members, we performed a genome-wide linkage analysis in
      which we were able to exclude linkage to the IBCG1 locus on chromosome 14q and
      obtain evidence of a novel locus on chromosome 2q37. Electronic supplementary
      material. The online version of this article (doi:10.1007/s12031-009-9287-3)
      contains supplementary material, which is available to authorized users.

PMID- 19757206
TI  - Strategies to resolve the catalytic mechanism of acetylcholinesterase.
AB  - Acetylcholinesterase (AChE) hydrolyzes its physiological substrate acetylcholine
      at one of the highest known catalytic rates. Two sites of ligand interaction have
      been identified: an acylation site or A-site at the base of the active-site gorge
      and a peripheral site or P-site at its mouth. Although much is known about AChE
      structure and the role of specific residues in catalysis, a detailed
      understanding of the catalytic mechanism and the role of the P-site has lagged
      far behind. In recent years, we have clarified how the P-site and A-site interact
      to promote catalysis. Our studies revealed that the P-site mediates substrate
      trapping and that ligand binding to the P-site can result in steric blockade of
      the A-site as well as allosteric activation of substrate hydrolysis. Because a
      general, nonequilibrium treatment of AChE catalysis results in complex enzyme
      kinetic formulations, three simpler, overlapping strategies are presented here
      that provide significant insights into the AChE catalytic mechanism. The
      strategies are (1) to choose substrates, preferably close analogs of
      acetylcholine, that render some intermediates in the general reaction scheme
      negligible; (2) obtain some of the thermodynamic parameters in this scheme with
      experiments that are independent of kinetic measurements.

PMID- 19757207
TI  - Adequacy and diagnostic accuracy of aspiration vs. capillary fine needle thyroid
      biopsies.
AB  - Thyroid nodules can be biopsied by fine needle aspiration (FNA) or fine needle
      capillary (FNC) biopsies. However, there is controversy on whether one technique
      is superior to another. In a randomized cytopathologist-blinded cross-sectional
      study, 260 patients (238 females, age 43.2 +/- 12.6) with nodular (82.7%) and
      diffuse goiter (17.3%) underwent 520 FNAs and 520 FNCs (not guided by
      ultrasound). Smears were scored for sample adequacy, and diagnosed as malignant,
      benign, suspicious, or nondiagnostic. Diagnostic accuracy was calculated based on
      the histological findings of 58 patients submitted to surgery. Intra-technique
      diagnostic accuracy and sample adequacy was seen in all samples. FNA and FNC
      provided similar cytological diagnosis, respectively (benign: 75.8% vs. 74.2%, p
      = 0.600; malignant: 3.8% vs. 3.8%, p = 0.871; suspicious: 10.4% vs. 10.8%, p =
      0.913; and nondiagnostic: 10.0% vs. 11.2%, p = 0.598). Adequacy scores were
      similar by FNA (7.94 +/- 2.84) and FNC (7.96 +/- 2.81, p = 0.909). The same
      proportion of adequate or superior samples was seen in both techniques (91.6%).
      Sensitivity was equal to 85.7% for FNA and 100% for FNC. Similarly, specificity
      was 100% for both techniques. FNA and FNC provide the similar sample adequacy and
      diagnostic accuracy. The choice of technique should be based on the operator's
      personal preferences and experience.

PMID- 19757208
TI  - Alzheimer's disease amyloid beta-protein and synaptic function.
AB  - Alzheimer's disease (AD) is characterized neuropathologically by the deposition
      of different forms of amyloid beta-protein (A beta) including variable amounts of
      soluble species that correlate with severity of dementia. The extent of synaptic
      loss in the brain provides the best morphological correlate of cognitive
      impairment in clinical AD. Animal research on the pathophysiology of AD has
      therefore focussed on how soluble A beta disrupts synaptic mechanisms in
      vulnerable brain regions such as the hippocampus. Synaptic plasticity in the form
      of persistent activity-dependent increases or decreases in synaptic strength
      provide a neurophysiological substrate for hippocampal-dependent learning and
      memory. Acute treatment with human-derived or chemically prepared soluble A beta
      that contains certain oligomeric assemblies, potently and selectively disrupts
      synaptic plasticity causing inhibition of long-term potentiation (LTP) and
      enhancement of long-term depression (LTD) of glutamatergic transmission. Over
      time these and related actions of A beta have been implicated in reducing
      synaptic integrity. This review addresses the involvement of neurotransmitter
      intercellular signaling in mediating or modulating the synaptic plasticity
      disrupting actions of soluble A beta, with particular emphasis on the different
      roles of glutamatergic and cholinergic mechanisms. There is growing evidence to
      support the view that NMDA and possibly nicotinic receptors are critically
      involved in mediating the disruptive effect of A beta and that targeting
      muscarinic receptors can indirectly modulate A beta's actions. Such studies
      should help inform ongoing and future clinical trials of drugs acting through the
      glutamatergic and cholinergic systems.

PMID- 19757209
TI  - Dietary supplementation with S-adenosyl methionine delays the onset of motor
      neuron pathology in a murine model of amyotrophic lateral sclerosis.
AB  - The full range of causative factors in Amyotrophic lateral sclerosis (ALS)
      remains elusive, but oxidative stress is recognized as a contributing factor.
      Mutations in Cu/Zn superoxide dismutase 1 (SOD-1), associated with familial ALS,
      promote widespread oxidative damage. Mice-expressing G93A mutant human SOD-1 mice
      display multiple pathological changes characteristic of ALS and are therefore
      useful for therapeutic development. Dietary supplementation with S-adenosyl
      methionine (SAM) has provided multiple neuroprotective effects in mouse models of
      age-related cognitive pathology. We examined herein whether SAM supplementation
      could affect the course of motor neuron pathology in mice-expressing mutant human
      SOD-1. SAM delayed disease onset by 2-3 weeks. SAM also delayed hallmarks of
      neurodegeneration in these mice and in ALS, including preventing loss of motor
      neurons, and reducing gliosis, SOD-1 aggregation, protein carbonylation, and
      induction of antioxidant activity. SAM did not increase survival time. These
      preliminary findings, using a single concentration of SAM, suggest that SAM
      supplementation maybe useful as part of a comprehensive therapeutic approach for
      ALS.

PMID- 19757211
TI  - DNA chip analysis in diverse organisms with unsequenced genomes.
AB  - Whether for basic research or biotechnology, DNA microarrays have become
      indispensable tools for studying the transcriptome. Normally, analyses begin with
      a set of known cDNA sequences to prepare microarray chips specific for a target
      organism with an extensively sequenced and annotated genome. For many organisms,
      however, genome programs are not complete or have not been initiated. The present
      study demonstrates that, whether using homologous or heterologous arrays, the
      chances of seeing interesting differences are similar. When a specific DNA
      microarray is not available, the results indicate that a reverse approach based
      on a heterologous array can be used to probe for interesting differences in gene
      expression. This may be sufficient in many studies but, if necessary, the genes
      exhibiting the most significant changes subsequently could be identified by
      traditional molecular approaches. Such a reverse strategy can provide a
      convenient and inexpensive approach to probe for significant genetic changes in
      many diverse studies, to monitor or mine critical biological information for
      basic or applied research, long before complete sequence data are available.

PMID- 19757212
TI  - Development of real time RT-PCR assays for detection of type A influenza virus
      and for subtyping of avian H5 and H7 hemagglutinin subtypes.
AB  - Rapid detection and subtyping of H5 and H7 subtypes influenza A viruses are
      important for disease control in poultry and potential transmission to humans.
      Currently, virus isolation and subsequent HA and NA subtyping constitute the
      standard for avian influenza viruses detection and subtype identification. These
      methods are highly accurate and sensitive but are also laborious and time
      consuming. Reverse transcription PCR and real time reverse transcription PCR
      assays, suitable tests for rapid detection, have previously been used for the
      specific diagnosis of H5 and H7 viruses, however, at present, no primer and probe
      sets are available for the identification of all H5 and H7 strains. Herein, we
      have developed specific and sensitive real time reverse transcription PCR assays
      for the detection of type A influenza virus and for subtyping of avian H5 and H7
      hemagglutinin subtypes and we have also compared these molecular assays with
      viral isolation in terms of sensitivity. Our results demonstrate that the real
      time reverse transcription PCR assays are more sensitive, specific, less
      expensive compared to viral isolation. In conclusion, molecular assays could
      represent an useful tool for rapid detection and screening of H5 and H7 isolates
      during influenza A virus outbreaks alternatively to viral isolation.

PMID- 19757213
TI  - Berberine inhibits acute radiation intestinal syndrome in human with abdomen
      radiotherapy.
AB  - Radiation-induced acute intestinal symptoms (RIAISs) are the most relevant
      complication of abdominal or pelvic radiation. Considering the negative impact of
      RIAIS on patients' daily activities, the preventive effects of berberine on RIAIS
      in patients were investigated. Thirty-six patients with seminoma or lymphomas
      were randomized to receive berberine oral (n = 18) or not (n = 18). Forty-two
      patients with cervical cancer were randomized to a trial group (n = 21) and
      control group (n = 21). Radiotherapy used a parallel opposed anterior and
      posterior. 300-mg berberine was administered orally three times daily in trial
      groups. Eight patients with RIAIS were treated with 300-mg berberine three times
      daily from the third to the fifth week. Toxicities, such as fatigue,
      anorexia/nausea, etc., were graded weekly according to CTC version 2.0. Patients
      with abdominal/pelvic radiation in the control group showed grade 1 fatigue,
      anorexia/nausea, colitis, vomiting, proctitis, weight loss, diarrhea and grade 2
      anorexia/nausea, fatigue. Only grade 1 colitis, anorexia/nausea, and fatigue were
      seen in patients of abdominal radiation treated with berberine. Grade 1 fatigue,
      colitis, anorexia/nausea, and proctitis occurred in patients of pelvic
      radiotherapy treated with berberine. Pretreatment with berberine significantly
      decreased the incidence and severity of RIAIS in patients with abdominal/pelvic
      radiotherapy when compared with the patients of the control group (P < 0.05).
      RIAIS were reduced in patients with abdominal radiotherapy/pelvic radiation after
      receiving berberine treatment. Berberine significantly reduced the incidence and
      severity of RIAIS and postponed the occurrence of RIAIS in patients with
      abdominal or whole pelvic radiation.

PMID- 19757210
TI  - Are there common biochemical and molecular mechanisms controlling manganism and
      parkisonism.
AB  - Over the past several decades there has been considerable progress in our basic
      knowledge as to the mechanisms and factors regulating Mn toxicity. The disorder
      known as manganism is associated with the preferential accumulation of Mn in the
      globus pallidus of the basal ganglia which is generally considered to be the
      major and initial site of injury. Because the area of the CNS comprising the
      basal ganglia is very complex and dependent on the precise function and balance
      of several neurotransmitters, it is not surprising that symptoms of manganism
      often overlap with that of Parkinson's disease. The fact that neurological
      symptoms and onset of Mn toxicity are quite broad and can vary unpredictably
      probably reflects specific genetic variance of the physiological and biochemical
      makeup within the basal ganglia in any individual. Differences in response to Mn
      overexposure are, thus, likely due to underlying genetic variability which
      ultimately presents in deviations in both susceptibility as well as the
      characteristics of the neurological lesions and symptoms expressed. Although
      chronic exposure to Mn is not the initial causative agent provoking Parkinsonism,
      there is evidence suggesting that persistent exposure can predispose an
      individual to acquire dystonic movements associated with Parkinson's disease. As
      noted in this review, there appears to be common threads between the two
      disorders, as mutations in the genes, parkin and ATP13A2, associated with early
      onset of Parkinsonism, may also predispose an individual to develop Mn toxicity.
      Mutations in both genes appear to effect transport of Mn into the cell. These
      genetic difference coupled with additional environmental or nutritional factors
      must also be considered as contributing to the severity and onset of manganism.

PMID- 19757214
TI  - Folic acid supplementation for the prevention of recurrence of colorectal
      adenomas: metaanalysis of interventional trials.
AB  - Conflicting data have emerged from preclinical and clinical studies that examined
      the relationship between folic acid and the risk of recurrence of colorectal
      adenomas. To determine precisely that relation, we planned this metaanalysis. We
      searched literature to identify interventional randomized, placebo-controlled
      studies where folic acid in specific dose and for specific duration was
      administered to evaluate its effect on the recurrence of adenomatous colorectal
      polyps. Five eligible trials were identified. The total number of patients with
      history of colorectal adenomas in the folate and the placebo groups was 805 and
      775 patients, respectively. Our analysis showed that folate supplementation had
      no protective effects on the recurrence of colorectal adenomas [odds ratio = 1.08
      (95% CI; 0.87, 1.33; P = 0.49)], nor has a positive outcome on the number of
      recurrent polyps per patient (P = 0.41). Examination of folic acid dose effect
      showed that the two studies that have used folic acid as 1 mg/day favored folic
      acid over placebo with an odds ratio of 0.62 (95% CI; 0.48, 0.80). However, the
      overall effect for all included studies was not significant [odds ratio = 0.78
      (95% CI; 0.49, 1.24; P = 0.30)]. We found significant heterogeneity between
      trials, moreover, included trials exhibit inconsistency in methodological
      quality. The present metaanalysis has failed to show potential benefit for folate
      supplementation. Future trials should examine the effect of different dosage and
      duration. Moreover, the confounding effect of dietary and life style habits
      should be carefully controlled.

PMID- 19757215
TI  - Efficacy and safety of sorafenib in patients with advanced renal cell carcinoma
      with and without prior cytokine therapy, a subanalysis of TARGET.
AB  - Before the development of targeted therapies, administration of cytokines (e.g.,
      interleukin-2, interferon-alpha) was the primary systemic treatment option for
      advanced renal cell carcinoma. Sorafenib, an oral targeted, multikinase
      inhibitor, significantly prolonged progression-free survival and overall survival
      in the Treatment Approaches in Renal Cancer Global Evaluation Trial (TARGET), a
      large (N = 903) phase III, double-blind, randomised, placebo-controlled study of
      patients with advanced renal cell carcinoma resistant to standard therapy. This
      analysis of a patient subgroup from TARGET evaluated the safety and efficacy of
      sorafenib in patients who had received prior cytokine therapy (sorafenib: n =
      374; placebo: n = 368) and in patients who were cytokine-naive (sorafenib: n =
      77; placebo: n = 84). Progression-free survival was significantly prolonged with
      sorafenib therapy compared with placebo among patients with and without prior
      cytokine therapy (respectively 5.5 vs. 2.7 months; hazard ratio, 0.54; 95%
      confidence interval, 0.45-0.64 and 5.8 vs. 2.8 months; hazard ratio, 0.48; 95%
      confidence interval, 0.32-0.73). Clinical benefit rates for sorafenib-treated
      patients compared with placebo patients were also higher (cytokine-treated: 83
      vs. 54.3%; cytokine-naive: 85.7 vs. 56.0%). Sorafenib was well tolerated in both
      subgroups (grade 3/4: 20 and 22%, respectively). Sorafenib demonstrated a
      consistent, significant clinical benefit against advanced renal cell carcinoma,
      with a twofold improvement in progression-free survival and disease control rate,
      with similar toxicities in patients with or without prior cytokine treatment.

PMID- 19757216
TI  - Prediction and identification of tumor-specific noncoding RNAs from human
      UniGene.
AB  - Noncoding RNAs (ncRNAs) have been proven to actively participate in many diverse
      biologic processes. Some ncRNAs are strongly associated with tumorigenesis and
      could thus be regarded as tumor markers, or even as candidate therapeutic
      targets. In this study, we computationally analyzed the human UniGene dataset to
      predict potential tumor-specific ncRNAs, and then verified our predictions
      experimentally. We demonstrated that two of our predicted ncRNAs showed tumor
      specific expression in non-small cell lung cancer and endometrial carcinoma,
      respectively. Genomic analysis of these two ncRNAs suggests that they might play
      significant roles in tumorigenesis and are therefore worthy of further
      investigation.

PMID- 19757217
TI  - A commentary on the possible association of Ljungan virus and SIDS and issues in
      SIDS research.

PMID- 19757218
TI  - Children, adolescents and young adults suicide data from Epirus, northwestern
      Greece.
AB  - The aim of this study was to evaluate suicide trends among individuals < or = 24
      years of age in the region of Epirus, northwestern Greece, from January 1998 to
      December 2008. Twenty-one cases were classified as suicides out of 242 total
      deaths (8.7%). The male to female suicide ratio was 4.25 (17 males and 4
      females). The preferred suicide method for those aged > or = 19 years involved
      firearms, and for those aged < 19 years was hanging. Alcohol was implicated in
      more than 50% of the suicides and was consumed exclusively by those aged > 16
      years. Suicides by self-shooting were more often related to drinking than
      suicides by other methods. Children and adolescents (aged up to 15 years), older
      adolescents (15-18 years) and young adults (19-24 years) had suicide rates of
      0.05/100,000, 0.10/100,000 and 0.39/100,000 inhabitants per year, respectively.
      These suicide rates are the lowest reported so far in Europe. The main reason for
      this may be the traditional lifestyle of the local population and the strong
      family ties that protect against suicide, especially for the young.

PMID- 19757220
TI  - [Quality of life in major depressive disorder: a cross-sectional study].
AB  - OBJECTIVE: To investigate quality of life and its association with depression in
      patients with major depressive disorder. METHOD: The study included 74 patients
      diagnosed with major depressive disorder according to DSM-IV. The Hamilton
      Depression Rating Scale (HAM-D) was used to assess the severity of depression;
      and the, Medical Outcomes Study Short Form-36 (MOS SF-36) and EuroQol 5-D (EQ-5D)
      were used to measure quality of life. RESULTS: In the assessment of quality of
      life, it was determined that Patients with major depressive disorder scored
      significantly lower on all domains of MOS SF-36 compared to Turkish normative
      data. The depressive disorder patients had lower EQ-5D health utility index
      scores, in comparison to Turkish normative data. There was a significant negative
      correlation between mean HAM-D score and all domains of MOS SF-36 and EQ-5D
      health utility index scores. When quality of life in depressive patients was
      compared according to episode type, patients with recurrent type major depressive
      disorder had lower quality of life in terms of physical functioning, general
      health perception, and physical component summary score than patients with single
      episode type major depressive disorder. CONCLUSION: All domains of quality of
      life were lower in patients with major depressive disorder and quality of life
      decreased as severity of depression increased. Physical health perception was
      impaired to a greater degree in patients with recurrent major depressive disorder
      when compared with single episode depressive patients.

PMID- 19757221
TI  - [The effect of firearms in inducing stress in high school students in the city of
      Duzce (Turkey)].
AB  - OBJECTIVE: This study aimed to examine the behaviors of high school students
      exposed to firearms and firearms- related violence, which they had perpetrated or
      witnessed, and whether or not these events were related to stress. METHOD: The
      study was conducted in Duzce province, which is characterised by the widespread
      use of firearms. A questionnaire was prepared to ascertain students' attitudes
      and behaviors towards owning firearms, their thoughts about firearms- related
      violence, and whether or not they had been a victim or witness to firearms-
      related violence. After a stress level scale was added to the questionnaire, it
      was administered to 791 students randomly chosen from the 8304 students that were
      attending all high schools in Duzce. The results were evaluated with using SPSS
      v.11.0 software. RESULTS: The level of stress in students that had contact with
      firearms, whether or not they were faced with a violent act, may be reached the
      adaptation difficulty level. Aggressive behaviors like hectoring occurred between
      coequal groups and brothers/sisters, affectedstress levels. Exposure to and
      witnessing violent acts had important roles on level of stress. Gender, income
      level, and lack of a private room at home for adolescents affected stress levels.
      Contrary to expectations, the presence of firearms at home or in their
      surroundings did not have an effect on stress levels. Hearing the sound of
      gunfire was one of the most important factors related to stress levels.
      CONCLUSION: Because of its ability to induce stress in adolescents, they must be
      protected form exposure firearms and their use, which is widespread in Duzce.

PMID- 19757222
TI  - [Identity confusion and psychopathology in late adolescence].
AB  - OBJECTIVE: The aim of this study was to investigate the relationship of identity
      confusion with clinical diagnoses and personality pathology. METHOD: Participants
      in the first part of the study were 950 high school students or graduates. The
      participants were 484 males and 466 females ranging in age between 16 and 25
      years of age (X = 18.3, sd = 0.8). We first administered the Instrument for
      Assessing Identity Confusion (IFAIC), and following a random sampling procedure
      we selected 30 participants with an IFAIC score > or = 1 standard deviation above
      the mean score to constitute the identity confusion group, and 30 participants
      with an IFAIC score < or = 1 standard deviation below the mean score to
      constitute the non-confusion group. The 60 participants included in the second
      part of the study were clinically assessed by means of SCID-I and SCID-II
      interviews. FINDINGS: The percentage of the participants receiving at least one
      axis I diagnoses was 73.3 % in the identity confusion group as opposed to 6.6 %
      in the non-confusion group. Likewise, participants in the identity confusion
      group fulfilled more personality disorder criteria than those in the non
      confusion group. When the groups were compared for each personality disorder
      criteria, significant differences were observed in terms of avoidant, dependent,
      obsessive-compulsive, self-defeating, borderline and schizotypal personality
      disorders. CONCLUSION: Findings of the present study do not support the view that
      identity confusion is a condition emerging exclusively in adolescents with
      borderline or psychotic personality organization.

PMID- 19757223
TI  - [Attitudes and behaviors of psychiatry residents and psychiatrists working in
      training institutes towards the relationship between the pharmaceutical industry
      and physicians].
AB  - OBJECTIVE: To determine the attitudes and behaviors of psychiatrists and
      psychiatry residents towards pharmaceutical representatives and their promotional
      activities, and to evaluate the effect of the duration of residency and type of
      the training institution on these attitudes and behaviors. METHOD: A validated
      questionnaire for assessing the attitudes and behaviors of physicians towards the
      pharmaceutical industry was administered to psychiatrists and psychiatry
      residents at regional meetings. Of the 1973 participants, 348 responded. RESULTS:
      Although there was significant interaction between psychiatrists and
      pharmaceutical representatives, 50.7% of psychiatrists reported that they thought
      these interactions had no impact on their prescribing practices. First- and
      second-year residents agreed more than the other residents and the specialist
      that pharmaceutical representatives provided accurate information and had no
      effect on physician prescribing practices. First- and second-years residents
      agreed less than older residents that pharmaceutical representatives used
      marketing techniques. The psychiatrists regarded most of the pharmaceutical
      promotions as appropriate. State hospital staff agreed more than the university
      hospital staff that the pharmaceutical industry should support educational
      meetings in their institutions. CONCLUSION: There was intense interaction
      (3/4)characterized by undefined boundaries (3/4)between psychiatrists and the
      pharmaceutical industry. Most physicians were not provided any guidelines
      concerning their interactions with pharmaceutical representatives and there was
      general concern about the necessity of restricting these interactions.

PMID- 19757224
TI  - [The relationship between cognitive intelligence, emotional intelligence, coping
      and stress symptoms in the context of type A personality pattern].
AB  - OBJECTIVE: This study aimed to determine the relationships between cognitive and
      emotional intelligence, coping and stress symptoms in the context of Type A
      personality pattern. METHOD: The Raven Progressive Matrices, Emotional
      Intelligence Questionnaire, Ways of Coping Inventory, Stress Symptoms Scale, and
      Type A Personality Scale were administered to 271 university students. Two
      groups, Type As and Type Bs were created according to the Type A Personality
      Scale scores and were compared in terms of their scores on the other scales that
      were administered. RESULTS: Our analyses showed that stress symptoms were
      negatively correlated with effective coping, stress management, and general mood
      dimensions of the Emotional Intelligence Questionnaire. They were also positively
      correlated with ineffective coping and Type A behaviors. Being female also
      significantly predicted stress symptoms. When the participants were grouped
      according to Type A Personality Scale scores as Type As and Type Bs, the
      regression analysis showed that the stress symptoms of Type As were significantly
      predicted by the insufficient use of effective coping styles and deficiencies in
      the general mood component of emotional intelligence, whereas the stress symptoms
      of Type Bs were predicted by the insufficient use of effective coping styles,
      overuse of ineffective coping styles, and increase in the intrapersonal abilities
      component of emotional intelligence. CONCLUSION: Stress symptoms can be related
      to the variables associated with personality styles. It is suggested that stress
      management programs for Type As should include exercises that increase emotional
      intelligence, especially the components of drawing pleasure from their life
      situation, being more positive, hopeful and optimistic.

PMID- 19757225
TI  - [The effects of visual imagery on adjustment and quality in life of hemodialysis
      patients].
AB  - OBJECTIVE: Relaxation and imagery techniques have been widely used among patients
      with chronic physical illnesses other than end stage renal failure (ESRF). Case
      studies and some controlled studies suggest that relaxation and imagery
      techniques can be successfully used with hemodialysis patients to improve their
      adjustment. Nonetheless, randomized controlled studies are needed to
      systematically examine this effect. METHOD: The present study examined the effect
      of a specific visual imagery technique on adjustment and quality of life in a
      sample of 153 hemodialysis patients. Control procedures included an active
      control and a no-treatment control. The former consisted of relaxation training
      and general imagery techniques. Outcome variables included beliefs about
      hemodialysis treatment, ways of evaluating life, emotional adjustment, and
      quality of life. The ESRF Beliefs Questionnaire, the Life Evaluation
      Questionnaire for Hemodialysis Patients, the Hospital Anxiety and Depression
      Scale, the Ladder Scale, and 2 SF-36 summary scales were used to measure these
      outcome variables. RESULTS: The findings show that the specific imagery
      intervention did not have an effect on emotional adjustment or quality of life,
      either post-treatment or at follow-up; however, the rate of patient compliance
      with the interventions was moderately high and patients reported that they were
      satisfied with the intervention procedures. CONCLUSION: The present study is the
      first randomized controlled intervention study of the effects of relaxation and
      imagery on adjustment in hemodialysis patients. The findings are discussed in
      terms of their implications for future studies as well as their limitations.

PMID- 19757226
TI  - [Theory of mind in schizophrenia spectrum disorders].
AB  - OBJECTIVE: To review studies that investigated theory of mind (ToM) deficits in
      schizophrenia spectrum disorders. METHOD: After a thorough literature search, 71
      studies were included in this review. Data regarding the relationship between
      ToM, and other cognitive skills, symptoms, and the impact of the state of illness
      were reviewed. RESULTS: ToM instruments used in schizophrenia spectrum disorders
      have some major psychometric limitations; however, previous research was still
      able to provide some important findings regarding mentalizing impairments in
      schizophrenia. While ToM deficits are more pronounced in the acute phase of
      illness, it seems to persist during periods of remission. There is also evidence
      of ToM deficits in the healthy relatives of schizophrenics, patients with
      delusional disorder and bipolar disorder (BD), and individuals with high
      schizotypy scores. ToM dysfunction might be secondary to other cognitive deficits
      in patients with schizophrenia that have a good prognosis, asymptomatic
      schizophrenia, delusional disorder, and BD. Other cognitive deficits do not seem
      to explain ToM dysfunction in patients with psychosis and severe negative
      symptoms. These findings support the contribution of impairment in both domain
      general and domain-specific mechanisms to ToM deficits in schizophrenia spectrum
      disorders. ToM deficits may be important for understanding poor social
      functioning and poor insight in psychotic disorders. CONCLUSION: While ToM is
      influenced by state variables, it might be an endophenotype of schizophrenia;
      however, ToM is likely to be an indicator of other frontal lobe-related
      endophenotypes. Longitudinal studies conducted with high-risk individuals are
      particularly important.

PMID- 19757227
TI  - [Genetic studies of bipolar disorder: a review].
AB  - Bipolar disorder is a severe mental illness that afflicts approximately 1% of the
      world's population, and is characterized by mood swings from elation to
      depression. Although the etiology of bipolar disorder remains unclear, heritable
      factors have been shown to be involved. Family, twin, and adoption studies
      suggest a genetic etiology. Molecular genetic studies also support a genetic
      component. Many chromosomal regions have been implicated by these molecular
      genetic studies, but no single susceptibility gene has been identified. These
      findings show that bipolar disorder has a complex genetic etiology in which
      multiple unidentified genes and environmental factors play an important role in
      its pathogenesis. Herein, molecular genetic studies of bipolar disorder are
      reviewed based on a search of Medline using the key words, bipolar, genetic, and
      chromosome. Studies with positive results for bipolar disorder were selected
      first. The findings from these molecular genetic studies are reviewed
      systematically, chromosome by chromosome. Causes of the differences between the
      reported findings and of non-replication are discussed. Finally, important
      factors for designing a genetic study of bipolar disorder are examined.

PMID- 19757228
TI  - [Chronic manganese intoxication due to methcathinone (ephedron) abuse: a case
      report].
AB  - Known as an occupational disease, chronic manganese intoxication is recently
      being observed among abusers of psychoactive substances. Methcathinone
      hydrochloride is obtained by combining ephedrine/pseudoephedrine and potassium
      permanganate. Various neuropsychiatric symptoms have been reported among Efedron
      users. Our patient is a 29 year old male, who was referred to our hospital from a
      state general hospital with a diagnosis of Conversion Disorder. He was
      hospitalized and preliminary diagnoses of Facititous Disorder, Conversion
      Disorder, Psychiatric Disorder due to a General Medical Condition and Antisocial
      Personality Disorder. He was abstinent from any substance for five years upon
      referral to our hospital and had a history of methcathinone abuse for 4.5 years.
      The backache dated back to 6 years ago and a disturbance of gait was added to the
      clinical picture. A speech disturbance, falling while walking downhill and
      walking on tiptoe were added in the last 2-3 years. In the neurological
      examination, extrapyramidal system findings, gait disturbance and the report on
      use of manganese compunds were found. The setting was changed from psychiatric
      ward to neuorology ward and evaluated by consultant neurologist. The case was
      diagnosed as ?Manganese Intoxication'. The aim of this report is to demonstrate
      and emphasize the importance of questioning the presence of manganese compounds
      in case of history of substance abuse. Other areas of interest are the shortage
      of data on the intravenous use of manganese and the cases reported in the
      literature coming from the former Soviet Union.

PMID- 19757229
TI  - [Folie a deux between two unrelated individuals].
AB  - Folie a deux is a rare condition characterized by transmission of delusions from
      a primary patient to another individual, usually a blood relative or spouse,
      while living in relative isolation. We report a case of folie a deux, which
      resembled folie communiquee, in a 37-year-old man that acquired it from an older
      woman (primary patient). Although not related by blood, the patient was
      emotionally very close to the woman and they shared common features, including
      grandiose delusions about the supernatural powers of the primary patient and
      persecutory delusions concerning office colleagues, as the woman had, and then
      neighbors, fellow villagers, and even family members. Behavioral changes were
      observed in the secondary patient as he started wearing strange clothing and
      peculiar ornaments, and neglected his personal hygiene. He also started following
      the same rituals and routines as the primary patient, and changed his religious
      practices, which he had followed devoutly since adolescence. He began seeking her
      opinion concerning almost all decisions he had to make, including personal and
      professional matters. Yet, unlike the usual clinical picture, they did not live
      in social isolation; rather, they lived in an apartment in a well-known
      residential area of the city and he regularly worked at his office until the late
      stage of illness. Premorbidly, there were no features suggestive of dependency or
      low intelligence in the secondary case. After separation from the primary case,
      improvement was observed about 7 weeks after beginning risperidone treatment (6
      mg/day).

PMID- 19757230
TI  - An analysis of toxicology and medical journal conflict-of-interest polices.
AB  - Basic science and medical journals are increasingly requiring authors to disclose
      financial interests they have in the subject matter of contributed articles and
      letters. A comparison of journal conflict-of-interest (COI) policies can provide
      insight into published reports of low compliance rates and inconsistencies in
      disclosures by the same author found in different journals. The objective of this
      article is to compare the criteria, specificity, and scope of COI polices in
      toxicology and medical journals. We studied the COI policies of 47 toxicology and
      180 medical journals catalogued in Ulrich's International Periodicals Directory
      for criteria of competing interests, types of submissions covered, monetary or
      time thresholds for reporting, and penalties for violations. Indicators were
      constructed for rating policy specificity, author discretion, and policy scope.
      Written COI policies were found in 87% if the toxicology and 84% of the medical
      journals; 15% and 28% of the toxicology and medical journals, respectively, were
      explicit about the type of content covered by the policy; 20% and 29%,
      respectively, included a monetary threshold for reporting purposes; the level of
      author discretion for reporting COIs was found to be high in 46% of the
      toxicology and 41% of the medical journals respectively. The level of specificity
      for more than 75% of the written journal COI policies for both fields was minimal
      or practically nil, and the scope of more than 80% of the policies was minimal to
      narrow. Lack of specificity, high author discretion, and restricted scope were
      found to be prevalent among COI policies of toxicology and medical journals.

PMID- 19757231
TI  - Research misconduct policies of scientific journals.
AB  - The purpose of this study was to gather information on the misconduct policies of
      scientific journals. We contacted editors from a random sample of 399 journals
      drawn from the ISI Web of Knowledge database. We received 197 responses (49.4%
      response rate): 54.8% had a policy, and 47.7% had a formal (written) policy;
      28.9% had a policy that only outlined procedures for handling misconduct, 15.7%
      had a policy that only defined misconduct, 10.2% had a policy that included both
      a definition and procedures; 26.9% of journals had a policy that was generated by
      the publisher, 13.2% had a policy that was generated by the journal, and 14.7%
      had a policy that was generated by another source, such as a professional
      association. We analyzed the relationship between having a policy and impact
      factor, field of science, publishing house, and nationality. Impact factor was
      the only variable with a statistically significant association with having a
      policy. Impact factor was slightly positively associated with whether or not the
      publisher had a policy, with an odds ratio of 1.49 (P < .0004) per 10 units
      increase in the impact factor, with a 95% confidence interval (1.20, 1.88). Our
      research indicates that more than half of scientific journals have developed
      misconduct policies, but that most of these policies do not define research
      misconduct and most of these policies were not generated by the journal.

PMID- 19757232
TI  - Ethics instruction increases graduate students' responsible conduct of research
      knowledge but not moral reasoning.
AB  - The purpose of this study was to assess the short-term effectiveness of ethics
      courses in enhancing responsible conduct of research (RCR) knowledge and moral
      judgment among graduate students in health-related disciplines. Forty-eight
      graduate students completed a questionnaire about research experience, knowledge
      and judgments about appropriate research practices, and a standardized test of
      moral judgment at the beginning and end of a semester-long ethics course.
      Knowledge about RCR but not moral judgment increased significantly in some areas.
      The results are discussed in terms of implications for RCR instruction and of
      future research designed to improve RCR instruction.

PMID- 19757233
TI  - The experimental study of polyelectrolyte coatings suitability for encapsulation
      of cells.
AB  - Living cells encapsulated in polymeric shells are receiving increasing attention
      because of their possible biotechnological and biomedical applications. The aim
      of this work is to evaluate how different polyelectrolyte coatings, characterized
      by different numbers of polyelectrolyte layers and by different polyelectrolyte
      conformations, affect the viability of encapsulated biological material. We
      demonstrate the ability to individually encapsulate HL-60 cells as well as rat
      pancreatic islets within polymeric shells consisting of different PE layers using
      the layer-by-layer process. Coating of HL-60 cells allows for surviving and
      functioning of cells for all applied PE as well as for different numbers of
      layers. The islets encapsulated in applied polyelectrolytes exhibited the lower
      level of mitochondrial activity as compared to non-encapsulated islets.
      Nevertheless, encapsulated islets exhibited comparable absorbance values during
      the whole period of culture. Polyelectrolyte coating seems to be a promising way
      of allowing capsule void volume minimization in a model of encapsulated
      biological material for local production of biologically active substances.

PMID- 19757234
TI  - Effects of chondrogenic microenvironment on construction of cartilage tissues
      using marrow stromal cells in vitro.
AB  - OBJECTIVE: To investigate whether it is feasible to use the chondrogenic
      microenvironment provided by cartilage cells to construct cartilage tissues in
      vitro with bone marrow stromal cells (BMSC). MATERIALS AND METHODS: We isolated
      and cultured BMSC and cartilage cells from Sprague Dawley rats (SD rats). The
      supernatant of cartilage culture was used as inducing solution to cause
      differentiation of BMSC from the second generation of cells cultured in vitro.
      Cells were examined seven days later, using immunohistochemistry to determine the
      expression of collagen specific to type II cartilage. RT-PCR was used to detect
      the expression of type II collagen and aggrecan mRNA. BMSC and cartilage cells
      were isolated from SD rats and cultured in vitro. The BMSC and cartilage cells in
      culture were mixed evenly in an 8:2 ratio and inoculated into a polyglycolic
      acid/polylactic acid (PGA/PLA) scaffold to a final concentration of 5.0x10(7)
      cells/ml. PGA/PLA preparations with pure cartilage cells or pure BMSC served as
      the positive and negative controls, respectively. The control group of low
      concentration cartilage cells consisted of PGA/PLA preparations containing
      cartilage cells at 20% of the above mentioned concentration (1.0x10(7) cells/ml).
      Samples were collected eight weeks later, at which time general observations, wet
      weight, and glycosaminoglycan (GAG) levels were determined, and histological and
      immunohistochemical examinations were performed. RESULTS: Immunohistochemistry
      showed the induction of BMSC type II collagen, and RT-PCR indicated the
      expression of type II collagen and aggrecan mRNA. In the mixed-cell group and the
      positive control group, pure mature cartilage cells were produced after eight
      weeks of culture in vitro, and the size and shape of the scaffold were maintained
      throughout the culture period. The two groups gave rise to newly generated
      cartilage cells essentially identical in appearance and histological properties.
      The immunohistochemical results showed that the cartilage cells of both groups
      expressed abundant cartilage-specific type II collagen. The average wet weight
      and GAG content were more than 70% of the values in the positive control group.
      Only an extremely small amount of immature cartilage tissue formed in local
      regions in the BMSC-only sample, and the scaffold was obviously shrunken and
      deformed. Although the wet weight of newly generated cartilage tissue in the low
      concentration cartilage cell sample reached 30% of the value of the positive
      control group, the scaffold was obviously shrunken and deformed. Only regional
      and discontinuous cartilage tissues were formed, and the amount of newly
      generated cartilage was obviously less than in the co-culture and positive
      control groups. CONCLUSIONS: Cartilage cells can provide a microenvironment for
      cartilage formation to some extent, and also effectively induce BMSC to
      differentiate into cartilage cells and form tissue-engineered cartilage in vitro.

PMID- 19757235
TI  - Strategic retrieval, confabulations, and delusions: theory and data.
AB  - Based on Moscovitch and Winocur's "working with memory" framework, confabulation
      is described as a deficit in strategic retrieval processes. The present paper
      suggests that only a confluence of deficits on multiple memory-related processes
      leads to confabulation. These are divided into three categories. Core processes
      that are unique to confabulation and required for its evolution include: (1) an
      intuitive, rapid, preconscious "feeling of rightness" monitoring, (2) an
      elaborate conscious "editor" monitoring, and (3) control processes that mediate
      the decision whether to act upon a retrieved memory. The second category is
      deficits on constitutional processes which are required for confabulation to
      occur but are not unique to it. These include the formation of erroneous memory
      representation, (temporal) context confusion, and deficits in retrieval cue
      generation. Finally, associated Features of confabulations determine the content
      "flavour" and frequency of confabulation but are not required for their
      evolution. Some associated features are magnification of normal reconstructive
      memory processes such as reliance on generic/schematic representations, and
      positivity biases in memory, whereas others are abnormal such as perseveration or
      source memory deficits. Data on deficits in core processes in confabulation are
      presented. Next, the apparent correspondences between confabulation and delusion
      are discussed. Considering confabulation within a strategic memory framework may
      help elucidate both the commonalities and differences between the two symptoms.
      Delusions are affected by a convergence of abnormal perception and encoding of
      information, associated with aberrant cognitive schema structure and disordered
      belief monitoring. Whereas confabulation is primarily a disorder of retrieval,
      mnemonic aspects of delusions can be described as primarily a disorder of input
      and integration of information. It is suggested that delusions might share some
      of the associated features of confabulation but not its core and constitutional
      processes. Preliminary data in support of this view are presented.

PMID- 19757238
TI  - Endometriosis - an European perspective.

PMID- 19757237
TI  - Polycystic ovaries, as defined by the 2003 Rotterdam consensus criteria, are
      found to be very common in young healthy women.
AB  - BACKGROUND: The criteria for polycystic ovaries (PCO) as defined by the 2003
      Rotterdam consensus are based on the follicle number and ovarian volume, which
      decrease with age. A study was performed to assess the influence of age on the
      PCO prevalence. In addition, the relation between follicle number and ovulation
      day was studied. METHODS: Assessments were done in a spontaneous menstrual cycle
      in 171 healthy volunteers. The ovulation day and cycle duration were recorded.
      Transvaginal ultrasonography was performed between cycle day 6 and 9 to determine
      the follicle number and ovarian volume. RESULTS: In the age groups between 18 and
      22, 23 and 27, 28 and 32, 33 and 37, and 38 and 40 years, the prevalence of PCO
      was 83-84%, 66-84%, 42-79%, 19-33%, and 0-33%, respectively. Most PCO subjects
      had ovulatory cycles. The follicle number and ovarian volume decreased with age.
      There was a positive correlation between the follicle number and the ovulation
      day. CONCLUSIONS: PCO were found to be very common in young women. The follicle
      number and ovarian volume decreased with age, and therefore also the PCO
      prevalence decreased with age. We believe the PCO criteria should be reconsidered
      and adapted to the woman's age. Ovulation occurred later with increasing follicle
      number.

PMID- 19757242
TI  - The results of adjuvant radiotherapy in endometrial carcinoma.
AB  - AIM: To examine the clinical characteristics and treatment outcomes in patients
      with endometrial cancer receiving adjuvant radiotherapy. METHODS: A total of 157
      patients who received postoperative radiotherapy (RT) between 1999 and 2008 were
      evaluated, retrospectively. The mean age was 59 years (34-82). All patients
      received RT following surgery. Stage distribution was as follows: 92 patients
      (59%) stage I, 21 patients (13%) stage II, and 44 patients (28%) stage III.
      RESULTS: Overall survival rate was 95% at 2 years and 84% at 5 years. By the end
      of follow up, 135 patients (86%) were disease-free, and 4 (2%) were alive with
      disease. Univariate and multivariate analyses identified stage, grade, and
      serosal involvement as significant predictors for overall survival. CONCLUSION:
      The results of our study suggests that early stage, low-grade endometrial cancer
      with no serosal involvement is associated with a better survival and adjuvant
      radiotherapy is a well tolerated and effective therapeutic option.

PMID- 19757243
TI  - Activation of NF-kappaB and COX-2 expression is associated with breakthrough
      bleeding in patients using oral contraceptives in extended regimens.
AB  - The objective of the present study was to determine whether there is an increase
      in endometrial inflammation associated with the occurrence of breakthrough
      bleeding in patients using an oral contraceptive in extended regimens. The
      presence of nuclear factor NF-kappaB and Cox-2 expression was determined by
      immunohistochemistry in endometrial samples removed by hysteroscopy from patients
      with breakthrough bleeding during continuous use of an oral contraceptive
      containing gestodene. All patients had a history of menorrhagia associated or not
      with the presence of uterine pathology. The percentage of endometria showing a
      positive staining reaction for NF-kappaB in cell nuclei was significantly higher
      in patients with breakthrough bleeding than in those with amenorrhea. Cox-2
      expression in the endometrium was also significantly more frequent in patients
      with breakthrough bleeding. The occurrence of breakthrough bleeding in patients
      with uterine pathology using combined oral contraceptives is associated with the
      activation of endometrial inflammation through the NF-kappaB pathway.

PMID- 19757244
TI  - Effects of adding luteinizing hormone activity to gonadotropin  releasing  
      hormone antagonist protocols may differ according to age.
AB  - OBJECTIVE: In spite of previous reports on the beneficial effects of adding
      exogenous luteinizing hormone (LH) activity to gonadotropin releasing hormone
      (GnRH) antagonist protocols for conventional in vitro fertilization (IVF) or
      intracytoplasmic sperm injection (ICSI), these effects in various age groups are
      still controversial. This study was performed to evaluate the clinical efficacy
      of adding LH activity to GnRH antagonist protocols according to patient's age.
      METHODS: In this medical record review, responses to controlled ovarian
      hyperstimulation (COH) and IVF/ICSI outcomes were compared between follicle
      stimulating hormone (FSH) alone and FSH supplemented with LH activity groups in
      women < or =35 years (n=135) and those 435 years (n=97), respectively. RESULTS:
      Estradiol level on hCG day in LH-added group was higher (2.150.6+1.345.1 pg/ml
      vs. 1.606.2+994.6 pg/ml, P=0.011) in women < or =35 years, while it did not
      differ in those 435 years. Less oocytes were retrieved in LH-added group of women
      435 years (8.1+6.5 vs. 5.7+3.0, P=0.013), however, this figure did not differ in
      those < or =35 years. Regardless of age, the clinical pregnancy rates were not
      different between the two groups. CONCLUSIONS: Supplementation of exogenous LH
      activity to GnRH antagonist protocols affects the COH outcomes. These LH-adding
      effects may vary according to patient's age.

PMID- 19757245
TI  - Computerized analysis of fetal heart rate in pregnancies complicated  by
      gestational diabetes mellitus.
AB  - OBJECTIVE: We evaluated the value of computerized cardiotocography (cCTG) in
      pregnancies complicated by gestational diabetes mellitus (GDM). Purpose of study.
      We studied fetal heart rate (FHR) recordings from 100 pregnant women affected by
      GDM on diet therapy, 60 pregnant women affected by GDM on insulin therapy and 100
      normal pregnant controls. The results were compared among the groups and related
      to neonatal umbilical artery cord blood analysis at birth. RESEARCH DESIGN AND
      METHODS: Baseline FHR and the duration of episodes of low variation were
      significantly higher in diabetic than in controls and were negatively related to
      umbilical artery glycemia at birth, whereas the short-term variation in diabetics
      was significantly lower than in controls and was positively related to.
      CONCLUSIONS: Our study demonstrates that GDM does impact FHR. The alteration is
      slight but evident; it reflects fetal wellbeing and correlate with neonatal
      reactivity. Only cCTG may allow to detect those slight but significant
      differences.

PMID- 19757246
TI  - A review of the neurotoxic effect of palmyrah flour.
AB  - The present review covers the history of the neurotoxic effect of palmyrah
      (Borassus flabellifer L). The chemical nature of the active synergists is isomers
      of a spirostane tetraglycoside containing three rhamnosyl residues and one
      glucosamine where the position of the NH(2) appears to be the difference in the
      saponins. As neurotoxicity has not been reported in humans consuming palmyrah
      flour, it is hypothesized that this may be due to one or more of the following: a
      species effect; the mode of processing flour and cooking palmyrah flour recipes
      containing these water-soluble and dry-heat decomposable saponin primary amines;
      frequency of consumption of palmyrah flour-based products; and the nutritive
      value of other dietary components. It is hypothesized that the Hepatotoxic
      syndrome as reported previously is due to a collective effect of a number of
      biologically active compounds, most of which are water-soluble saponins, like
      neurotoxins.

PMID- 19757247
TI  - The use of principle component and cluster analyses to differentiate banana pulp
      flours based on starch and dietary fiber components.
AB  - Flour prepared from green and ripe Cavendish and Dream banana fruits were
      assessed for total starch, digestible starch, resistant starch, total dietary
      fiber, soluble dietary fiber and insoluble dietary fiber. Principle component
      analysis identified only one component responsible for explaining 83.83% of the
      total variance in the starch and dietary fiber components data to indicate that
      ripe banana flour had different characteristics from the green. Cluster analysis
      applied on similar data obtained two statistically significant clusters of green
      and ripe banana to indicate difference in behaviors according to the stages of
      ripeness. In conclusion, starch and dietary fiber components could be used to
      discriminate between flour prepared from fruits of different stage of ripeness.
      Results are also suggestive of the potential of green as well as the ripe banana
      flour as functional ingredients in food.

PMID- 19757248
TI  - Effect of banana pulp and peel flour on physicochemical properties and in vitro
      starch digestibility of yellow alkaline noodles.
AB  - The present study describes the utilization of banana--Cavendish (Musa acuminata
      L., cv cavendshii) and Dream (Musa acuminata colla. AAA, cv 'Berangan')--pulp and
      peel flours as functional ingredients in yellow alkaline noodles. Noodles were
      prepared by partial substitution of wheat flour with ripe banana pulp or peel
      flours. In most cases, the starch hydrolysis index, predicted glycaemic index
      (pGI) and physicochemical properties of cooked noodles were affected by banana
      flour addition. In general, the pGI values of cooked noodles were in the order;
      banana peel noodles < banana pulp noodles < control noodles. Since the peel flour
      was higher in total dietary fibre but lower in resistant starch contents than the
      pulp flour, the low pGI of banana peel noodles was mainly due to its high dietary
      fibre content. In conclusion, banana pulp and peel flour could be useful for
      controlling starch hydrolysis of yellow noodles, even though some physicochemical
      properties of the noodles were altered.

PMID- 19757249
TI  - Omega-6 (n-6) and omega-3 (n-3) fatty acids in tilapia and human health: a
      review.
AB  - A recent publication questions the nutritional value of tilapia in the human diet
      following the movement to eat fish for their omega fatty acid (FA) content. It
      suggests that tilapia have an elevated amount of omega-6 FAs (n-6) and a
      deficient amount of omega-3 FAs (n-3), a possibly unhealthy proportion for
      humans. A high n-6:n-3 ratio is problematic because too much arachidonic acid, an
      n-6 FA, promotes inflammation, which aggravates heart disease and other
      illnesses. This paper analyzes the numbers from different tilapia composition
      studies in an effort to understand the range of n-6 and n-3 totals and ratios
      present in both farmed and wild tilapia. Generally, wild tilapia have more n-3
      FAs than farmed tilapia, but diet adjustments can alter the body composition of
      the domesticated variety. Consumers should consider fish as part of a balanced
      diet and evaluate their FA needs on an individual basis.

PMID- 19757250
TI  - Assessment of energy intake of infants exclusively fed with infant formulae
      available on the European market.
AB  - The aim of the present study was to assess the total daily energy intake of
      infants (aged 0-4 months) exclusively fed with infant formulae available on the
      European Union market. All of the products were identified from the European
      market share data of the year 2007 covering 22 countries. The calculated daily
      energy intake based on the instructions labelled on these products was compared
      with the energy requirements based on World Health Organization recommendations,
      considering the standard body weight established by the Food and Agriculture
      Organization. In addition, the daily energy intake was also calculated based on
      direct measurements of the amount of formulae contained in the spoon provided by
      the supplier. It was found that the kcal/day intakes provided by the supplier
      were higher than the values recommended by international organizations. The
      energy intake values calculated based on the direct spoon measurements were even
      higher.

PMID- 19757256
TI  - Editorial comment.

PMID- 19757257
TI  - The rationale for the use of measles post-exposure prophylaxis in pregnant women:
      a review.
AB  - A review of published literature was undertaken to investigate the maternal and
      fetal effects of measles infection in pregnancy and to inform the need for post
      exposure prophylaxis. There is no evidence to support an association between
      measles in pregnancy and congenital defects. However, the need for effective post
      exposure protection is supported by studies suggesting a high risk of severe
      maternal morbidity, fetal loss and prematurity. Measles in late pregnancy can
      also lead to perinatal infection in the infant, which may be associated with a
      high mortality and the risk of subacute sclerosing panencephalitis. UK guidance
      recommends using human normal immunoglobulin for susceptible pregnant women
      exposed to measles. Although there is no direct evidence that this will reduce
      the complications of measles in pregnancy, it may attenuate disease and therefore
      reduce the rate of complications. Measures to identify women likely to be
      susceptible include assessment of age, vaccination history, and/or antibody
      testing.

PMID- 19757258
TI  - The pathophysiology of pre-eclampsia: current clinical concepts.
AB  - Despite decades of intense research on the problem, pre-eclampsia remains one of
      the great mysteries of medical science. This paper is an overview of the existing
      knowledge on the disease that unifies the essential and validated findings of
      past and current scientific investigation. A key focus has been an attempt to
      distinguish foundationally pathogenic mechanisms from multiple epiphenomena that
      continue to be elucidated. The hypothesis was developed after taking into
      consideration the various known risk factors for pre-eclampsia, epidemiologic
      trends, and the most available research to date regarding the pathogenesis of the
      disease. In summary, it may be stated that pre-eclampsia is a systemic disease of
      maternal endothelial cell dysfunction, resulting from a deficient endovascular
      invasion of fetal extravillous cytotrophoblasts into the maternal spiral
      arterioles--a process facilitated by cytokine and angiogenic factor producing
      uterine/decidual CD56bright Natural Killer (NK) cells and impeded by the more
      cytotoxic peripheral CD56dim NK cells of the innate immune system. Therefore, the
      disease process appears to be fundamentally one of a unique variant of immune
      maladaptation at the level of the maternal-fetal interface in the setting of more
      or less susceptible persons caused by a mixture of both insufficient maternal
      tolerance induction to the paternal antigens and unfavourable combinations of
      genetically determined maternal leukocyte receptors and fetal antigens.

PMID- 19757259
TI  - Urine HPV-DNA detection for cervical cancer screening: prospects and prejudices.
AB  - Oncogenic types of human papilloma viruses (HPVs) have been established to be the
      causative agents for cervical cancers and high-grade squamous intraepithelial
      lesions (HSILs). The clinical application of molecular tests for HPV detection
      for screening purposes has been of considerable interest. DNA amplification
      methods allow the use of self-collected samples (including urine) from material
      collected away from the original disease site. For screening of cervical
      pathology, detection of HPV-DNA in urine would be useful only if it represents
      cervical HPV infection and/or HPV-related cervical pathology. We conducted a
      review of the literature in order to ascertain: (1) if urine is an adequate
      sample for HPV-detection; (2) whether sensitive techniques are available for HPV
      detection in urine and (3) if detection of HPV in urine truly represents cervical
      infection/pathology. The review process consisted of assembling facts and
      analysing the published literature on the following facts: anatomical
      considerations of the lower genital and the lower urinary tract, biological
      behaviour of HPV and its shedding behaviour, technical issues regarding sample
      collection, processing and HPV-DNA assay systems, concordance rates of HPV-DNA
      detection and their type specificity in the paired samples (urine and cervical
      scrapes) obtained in different clinico-epidemiological settings and comparative
      detection rates of HSILs in the paired samples.

PMID- 19757260
TI  - Endometriosis: the elusive epiphenomenon.
AB  - The denervation-reinnervation view proposes that retrograde menstruation results
      from loss of normal, fundocervical polarity caused by injuries to uterine nerves.
      Injuries may be sporadic (following vaginal delivery) or recurrent (after
      persistent straining during defaecation) creating very different appearances at
      laparoscopy. Clinical symptoms of pelvic pain, menstrual problems, dyspareunia,
      and dysmenorrhoea result from aberrant reinnervation that may occur with, or
      without deposits of pelvic endometriosis. Endometrium, delivered by retrograde
      menstruation, adheres to any injured tissues in the lower pelvis. Classical
      'endometriosis' is largely an epiphenomenon to underlying processes of
      denervation and reinnervation.

PMID- 19757261
TI  - Adherence and tolerability of iron-containing prenatal multivitamins in pregnant
      women with pre-existing gastrointestinal conditions.
AB  - Prenatal multivitamin supplements (PMS) are recommended during pregnancy.
      Suboptimal adherence in women experiencing gastrointestinal (GI) conditions is
      thought to be attributed to the high elemental iron content in PMS. This study
      sought to quantify adherence and tolerability of iron-containing PMS in women
      with pre-existing GI conditions by recruiting women who called the Motherisk
      Helpline. Women with (n = 36) and without (n = 166) pre-existing GI conditions
      were randomised to either PregVit (n = 106) or Orifer F (n = 96). Monthly follow
      up interviews were conducted to assess pill intake and GI adverse effects
      associated with PMS. The results of our study suggest that with the use of small
      size and low dose iron PMS, women with pre-existing GI conditions do not
      experience (1) more GI adverse effects, (2) lower adherence than women with no
      such conditions, and (3) may experience less severe nausea and vomiting of
      pregnancy. Supplementing with small tablets of low dose iron PMS should be
      considered.

PMID- 19757262
TI  - Conjoint twinning in the Maltese Islands.
AB  - Conjoined twinning is a relatively rare event in any community, with a rate of
      1.58 per 100,000 maternities reported in the EUROCAT database. The present study
      reviews the historical records for conjoined twins born in a closed Central
      Mediterranean archipelago population with particular reference to the last three
      decades. While the natural monozygotic twinning rates in the Maltese Islands
      corresponds to that reported from other communities, the incidence of conjoined
      twinning in the Maltese Islands has been shown by the present study to be
      significantly 2.5-times higher than that reported by the remaining EUROCAT
      contributors. The rate reported from the Maltese Islands by this review is 3.98
      per 100,000 maternities.

PMID- 19757263
TI  - Symphysiofundal height growth curve and growth velocity in pregnant women in a
      Nigerian community.
AB  - A prospective survey of symphysiofundal height (SFH) was undertaken in 202
      Nigerian pregnant women in Uromi, Edo State, Nigeria, with the objective of
      constructing an SFH growth chart for the pregnant population in the community. A
      customised gravidogram and a growth velocity curve were also constructed and
      compared with those derived in other regions of the world. The average SFH growth
      rate between 20 and 40 weeks was 0.8 cm/week. The gradient of the curve was not
      constant and the SFH growth rate changed with the progression of pregnancy. While
      the average SFH growth rate between 20 and 36 weeks was 0.9 cm/week, from 36 to
      40 weeks there was a marked deceleration to 0.3 cm/week. The average deviation
      from the mean SFH was 1.96 cm. It is recommended that regional customised
      gravidograms be derived for different pregnant populations which should be
      reviewed periodically. With this, routine SFH assessments can help in early
      detection of fetal growth rate anomalies based on an understanding of the
      peculiarities of fetal growth patterns in each community.

PMID- 19757264
TI  - Infants of diabetic mothers with abnormal fetal growth missed by standard growth
      charts.
AB  - Diabetic pregnancies may result in fetal macrosomia when glycaemia is poorly
      controlled, and when associated with diabetic vasculopathy, with small for
      gestational age (SGA) neonates. Both groups of infants have high neonatal
      morbidity. As fetal growth depends on maternal genetic influences, ethnic group
      or parity, relying exclusively on population-based growth charts may wrongly
      categorise the growth pattern of these infants. We compared neonatal morbidity
      and mortality of a cohort of 214 infants of diabetic mothers (IDM), identified
      either by population standards or by customised birth weight percentiles
      (adjusted for maternal height, booking weight, parity, ethnic origin, gestational
      age at delivery and sex). A total of 68 (31.8%) were diagnosed with macrosomia,
      11 (16%) of whom were identified by the customised growth method alone, and 16
      were diagnosed as SGA (7.5%), of whom the majority (13 or 81.2%) were identified
      by the customised growth method alone. None had increased mortality and
      morbidity.

PMID- 19757265
TI  - Prevalence and significance of antiphospholipid antibodies in selected at-risk
      obstetrics cases: a comparative prospective study.
AB  - In a prospective comparative study we screened 112 women with a past history
      either of pre-eclampsia, eclampsia, recurrent abortion, IUGR, IUFD or abruptio
      placentae, with no apparent aetiology and a demographically matched cohort of 106
      women having a past history of uncomplicated pregnancy outcome for the presence
      of antiphospholipid antibodies (aPL) and their significance. In the former group,
      the prevalence of aPL ranged from 10-46.87% compared with 8.49% in the later
      group. In women with the presence of aPL, the incidence of pre-eclampsia, early
      onset pre-eclampsia and abruptio placentae were 25%, 14.58% and 18.75%,
      respectively. In the same group, the abortion rate was 25% and live-birth rate
      was 64.58% with IUFD rate of 10.42%. Fetal morbidity rates were also higher in
      the mothers with aPL positivity, the incidence of IUGR was 27.08% and
      oligohydramnios was 33.33% in them. All these complications were statistically
      significant when compared with those of aPL negative mothers.

PMID- 19757266
TI  - Maternal and perinatal outcomes of eclampsia in Gadarif Hospital, Sudan.
AB  - This study aimed to investigate the incidence of eclampsia and its maternal and
      perinatal outcome in the Hospital of Obstetrics and Gynecology at Gadarif, Sudan
      from March 2007 to April 2009. There were 45 cases of eclampsia in 8,894
      deliveries (5/1,000). Some 62% of first convulsions occurred antepartum, 15.5%
      occurred intrapartum, and the rest (11.1%) occurred postpartum. Ten patients died
      and there were 16 (35.5%) perinatal deaths; eight of these were stillbirths and
      eight were early neonatal deaths.

PMID- 19757267
TI  - Cardiac troponin levels in pregnant women with severe pre-eclampsia.
AB  - Pre-eclampsia is a multisystem disorder that involves vascular endothelial
      dysfunction and diffuse inflammatory response. The cardiac troponin (cTn-I)
      levels in pre-eclampsia are controversial. The objective of this study was to
      compare the cTn-I levels between normal pregnant women and those with severe pre
      eclampsia. A total of 78 patients who underwent caesarean section were included
      in the study. The patients were assigned into two groups as the severe pre
      eclamptic pregnant group (study group, n = 36) and normotensive pregnant group
      (control group, n = 42).The cTn-I levels of all patients were measured
      preoperatively and postoperatively. A statistically significant difference was
      not determined between the preoperative and postoperative cTn-I levels (p > 0.05)
      between the two groups. In the present study, a relation was not determined
      between pre-eclampsia and increased cTn-I levels. If high cTn-I levels are
      determined in pre-eclamptic patients, other pathologies that may cause myocardial
      damage should be investigated.

PMID- 19757268
TI  - Decreased hepatic perfusion in patients with HELLP syndrome.
AB  - A total of 20 women with HELLP syndrome (haemolysis, elevated liver enzymes and
      low platelets), and 20 gestational age-matched healthy controls participated in
      this study which was conducted at Assiut University Maternity Hospital, Egypt.
      Dual hepatic perfusion was assessed by evaluation of hepatic artery blood flow
      and portal vein blood flow. The total liver blood flow was taken as the sum of
      flow volumes in the common hepatic artery and portal vein as assessed by Doppler
      ultrasound. The total liver blood flow decreased significantly in women with
      HELLP syndrome, compared with controls.

PMID- 19757269
TI  - Primary atony of the lower uterine segment as a distinct cause of early
      postpartum haemorrhage: a case series and management recommendations.
AB  - Primary atony of the lower uterine segment appears to be a distinct cause of
      postpartum haemorrhage. We report a case series of women with postpartum
      haemorrhage where ultrasound and clinical findings revealed a well contracted
      fundus and upper uterine segment and a ballooned out lower uterine segment, a
      condition we have called primary atony of the lower uterine segment. We hope that
      this case series will lead to increased recognition of this condition, stimulate
      others to report their experience and lead to additional studies to better
      characterise this entity, and develop more effective therapies.

PMID- 19757270
TI  - The effect of sublingual misoprostol versus intravenous oxytocin in reducing
      bleeding after caesarean section.
AB  - In this study, 100 singleton pregnant women underwent a caesarean delivery under
      general anaesthesia and were studied in terms of postpartum bleeding using
      oxytocin or misoprostol. Patients were randomly divided into two equal groups.
      One group received two tabs of misoprostol 200 microg sublingually and the second
      group took intravenous infusion of 20 units of oxytocin at the rate of 10 cc/min
      immediately after delivery until full contraction of the uterine. The amount of
      blood loss was lower in misoprostol group comparing with oxytocin group (608.91
      ml vs 673.9 ml) (p = 0.048) and this difference was statistically significant.
      The need to give additional oxytocin therapy in oxytocin group (36%) was
      significantly higher than misoprostol group (14%) (p = 0.032). It seems that the
      efficacy of sublingual misoprostol is equivalent to that of low dose intravenous
      oxytocin in reducing postpartum haemorrhage at caesarean section. Misoprostol has
      some other advantages like long shelf -life, stability at room temperature and
      oral use.

PMID- 19757271
TI  - Currently performed continence surgery: how useful are hospital episode
      statistics?
AB  - The aim of this study was to examine current trends in selecting continence
      operations for female patients in the UK. An online data search was carried out
      using the Hospital Episode Statistics website (www.hesonline.nhs.uk). Only
      operations performed on women were included. A request for more detailed
      information was submitted but no information was provided. Data were available
      for 4 years, from 2002-2003 until 2005-2006. It was difficult to establish trends
      regarding mid-urethral slings, including tension-free vaginal tape and
      transobturator tape, both inside out and outside in, as well as single incision
      slings. A respectable number of operations were coded as other specified and
      unspecified. The poor specificity of codes used and delayed availability of data
      precluded obtaining clear information about trends in the surgical management of
      urinary incontinence in women. There is a need to develop new codes that match
      changes in continence surgery and to provide data at the end of each financial
      year. This will help monitoring performance, audit as well as research.

PMID- 19757272
TI  - Menopause and urogynaecology service standards: a UK consultant-based
      questionnaire survey of RCOG recommendations.
AB  - A postal questionnaire of UK consultant obstetricians and gynaecologists was
      performed to evaluate the number of hospitals which met the Royal College of
      Obstetricians and Gynaecologists recommended standards for urogynaecology and
      menopause services. A total of 359 responses were analysed. Sixty-four percent of
      the consultants worked in units with direct referral systems from primary care
      continence services, while 63% of the consultants worked in units without a
      dedicated menopause clinic integrated with other women's health facilities. Most
      of the criteria assessed for clinical service standards in these fields are not
      met.

PMID- 19757273
TI  - Aspects of psychosocial problems of patients with vesico-vaginal fistula.
AB  - Our objective was to evaluate psychosocial problems among patients presenting
      with vesico-vaginal fistula (VVF), and their close relatives. All patients
      presenting with VVF and their spouses or attendant close relatives were
      administered a structured questionnaire followed by an in-depth interview. A
      total of 20 patients and 10 attendant relatives were interviewed. The average age
      of patients was 24.7 years, range 16-38 years. A total of 11 patients (55%) had
      their first marriage between the ages of 15-20 years, with one nulliparous,
      unmarried patient, who acquired VVF following infertility treatment with herbs.
      Of the interviewed respondents, 19 affirmed that prolonged labour was the cause
      of VVF, while four patients developed VVF sequel to unsupervised vaginal birth
      after a previous caesarean section. Reported medical problems were dermatitis
      (20%), foul smell of urine (15%), recurrent UTI (10%), infertility (5%),
      amenorrhoea (5%), in that order. Socially, 45% felt ostracised and 50% were
      economically impoverished by job loss. The divorce rate was 25%, with one case of
      remarriage and childbirth with an unrepaired VVF. Some 56.6% respondents
      suggested hospital delivery was a preventive measure, while 33.3% felt avoidance
      of premarital sex and early marriage would prevent VVF. VVF is still a major
      social and reproductive health problem and most patients and relatives understand
      the place of difficult childbirth in VVF formation. The need to empower patients
      to timely access standard maternity and emergency obstetric care is recommended.

PMID- 19757274
TI  - Vulvodynia, a step-wise therapeutic prospective cohort study.
AB  - Vulvodynia is characterised by the presence of vulval allodynia (pain evoked by
      non-painful stimuli) and vulval dysaesthesias (burning, soreness, rawness,
      stinging and irritation). We assessed a protocol for the evaluation and
      management of vulvodynia. The protocol was based on the most recent evidence
      available. We began a simple evaluation and proceeded to an aggressive one. From
      the cohort of 74 patients, 69 patients (93.2%) were adherent to the protocol. A
      total of 25 patients (36.3%) improved after antibiotic therapy: 14 patients
      (20.4%) had a positive fungal culture and 11 patients (15.9%) had a positive
      bacterial culture; none with a positive viral culture. Eight patients (11.6%)
      improved with dietary modification. Ten patients (14.5%) benefitted from
      tricyclic medications; 13 patients (18.8%) improved after gabapentin therapy; 13
      patients (18.8%) did not show improvement of their condition. Some 56 patients
      (81.2%) manifested an improvement of their symptoms, which allowed them to
      achieve painless sexual intercourse.

PMID- 19757275
TI  - Metformin in the treatment of clomiphene citrate-resistant women with polycystic
      ovary syndrome undergoing in vitro fertilisation treatment: a randomised
      controlled trial.
AB  - This study was conducted to determine the efficacy of metformin vs placebo in
      women with polycystic ovary syndrome (PCOS) undergoing IVF treatment. A total of
      66 CC-resistant patients were studied prospectively. The women were randomly
      assigned to receive 850 mg of metformin (n = 34) or placebo (n = 32) twice daily
      that started 1 month before commencing the IVF treatment and continued to the day
      of the pregnancy test. Compared with the metformin-treated group, women who
      received a placebo had a significant increase in terms of days of stimulation
      with HMG, number of HMG ampoules, number of follicles >14 mm, number of oocytes
      retrieved, number of mature eggs, fertilisation rate and oestradiol level on the
      day of hCG administration. Similarly, women in the placebo group showed a
      significant increase in poor quality embryos, cancellation rate and the rate of
      ovarian hyperstimulation syndrome, as compared with the metformin-treated group.
      On the other hand, women who received metformin showed a significantly higher
      number of good quality embryos and implantation rate when compared with the
      placebo controls. Despite the transfer of a similar number of embryos, an
      insignificant increased in the pregnancy rate along with significant reduction in
      the abortion rate was observed in the metformin-treated group as compared with
      the placebo controls. No fetal abnormalities were encountered in the babies born
      in the metformin-treated group. It is concluded that metformin affects positively
      the quality of both oocytes and embryos without a significant increase in the
      pregnancy rate. It decreases significantly the rates of abortion and ovarian
      hyperstimulation syndrome.

PMID- 19757276
TI  - Do consultant obstetricians and gynaecologists comply with motor traffic
      regulations when recalled to hospital to attend emergencies? A national audit.
AB  - Consultant obstetricians and gynaecologists are often recalled from home back
      into hospital to attend emergencies. We audited their driving practices and
      compliance to motor traffic regulations on recall to these emergencies with the
      aid of a questionnaire survey. A total of 218 of the 300 UK consultants surveyed
      responded. Some 65% of those who owned a green warning light beacon (GWL)
      admitted to speeding on some journeys and 46% ignored red lights; 84% of non
      owners of a GWL would speed and 28% would ignore a red light. A total of 37
      consultants had been stopped for traffic violations, nine with a GWL and 28
      without. Five consultants had been involved in accidents returning to hospital to
      attend an emergency. Obstetricians and gynaecologists are disregarding motor
      traffic regulations in order to attend emergencies.

PMID- 19757277
TI  - Porphyria: a rare cause of abdominal pain in pregnancy.

PMID- 19757278
TI  - Use of inhalable insulin in pregnancy.

PMID- 19757279
TI  - Pregnancy outcome after bilateral ligation of internal iliac artery.

PMID- 19757280
TI  - Myelodysplasia diagnosed during pregnancy with temporary haematological
      improvement after delivery.

PMID- 19757281
TI  - Successful pregnancy following conservative surgery for early stage ovarian
      cancer in a 36-year-old woman: a case report.

PMID- 19757282
TI  - Desmoid tumour of the rectus abdominis muscle during pregnancy.

PMID- 19757283
TI  - Maternal death due to ruptured diaphragmatic hernia.

PMID- 19757284
TI  - A case of hyperreactio luteinalis with peripartum subacute ovarian accident.

PMID- 19757285
TI  - Bowel obstruction in the postpartum period as a result of caecal volvulus around
      a large uterine leiomyoma.

PMID- 19757286
TI  - Nicorandil associated vulval and inguinal ulceration.

PMID- 19757287
TI  - Consent and reproductive health in schizophrenia: how much does the patient
      decide?

PMID- 19757288
TI  - A heavily pigmented vaginal perivascular epithelioid cell neoplasm.

PMID- 19757289
TI  - Re: Ikechebelu JI, Obi RA, Udigwe GO, Joe-Ikechebelu NN. 2005. Comparison of
      carbon dioxide and room air pneumoperitoneum for day-case diagnostic laparoscopy.
      Journal of Obstetrics and Gynaecology 25:172-173.

PMID- 19757291
TI  - Measurements of airborne methylene diphenyl diisocyanate concentration in the
      U.S. workplace--comment.

PMID- 19757292
TI  - Molds and mycotoxins in indoor environments--a survey in water-damaged buildings.
AB  - Mycotoxins are toxic, secondary metabolites frequently produced by molds in water
      damaged indoor environments. We studied the prevalence of selected, potent
      mycotoxins and levels of fungal biomass in samples collected from water-damaged
      indoor environments in Sweden during a 1-year period. One hundred samples of
      building materials, 18 samples of settled dust, and 37 samples of cultured dust
      were analyzed for: (a) mycoflora by microscopy and culture; (b) fungal chemical
      marker ergosterol and hydrolysis products of macrocyclic trichothecenes and
      trichodermin (verrucarol and trichodermol) by gas chromatography-tandem mass
      spectrometry; and (c) sterigmatocystin, gliotoxin, aflatoxin B(1), and satratoxin
      G and H by high performance liquid chromatography-tandem mass spectrometry. Sixty
      six percent of the analyzed building materials samples, 11% of the settled dust
      samples, and 51% of the cultured dust samples were positive for at least one of
      the studied mycotoxins. In addition, except in the case of gliotoxin, mycotoxin
      positive building material samples contained 2-6 times more ergosterol than
      mycotoxin-negative samples. We show that (a) molds growing on a range of
      different materials indoors in water-damaged buildings generally produce
      mycotoxins, and (b) mycotoxin-containing particles in mold-contaminated
      environments may settle on surfaces above floor level. The mass spectrometry
      methods used in this study are valuable tools in further research to survey
      mycotoxin exposure and investigate potential links with health effects.

PMID- 19757293
TI  - Beryllium aerosol characteristics in the magnesium and aluminum transformation
      industry in Quebec: a comparison of four different sampling methodologies.
AB  - To examine the influence of the sampling method on beryllium (Be) exposure
      assessment, a study was conducted in foundries and smelters to contrast the
      performance of five different dust sampling devices. Six sampling surveys were
      conducted in four different settings, and both personal and fixed station samples
      were collected using the following sampling heads: IOM samplers (inhalable dust),
      35-mm plastic cassettes (total dust), aluminum SKC cyclones (respirable dust), 8
      stage Sierra cascade impactors, and 12-stage MOUDI impactors. In total, beryllium
      concentrations were determined for 66/68 inhalable dust samples, 62/62 total dust
      samples, 56/57 respirable dust samples, 54/64 8-stage Sierra samples, and 19/25
      12-stage MOUDI samples. In the magnesium foundry and aluminum smelters, the
      concentrations obtained during specific tasks could exceed the actual permissible
      exposure limit of the province of Quebec (0.15 microg/m(3)) or of the ACGIH
      threshold limit value (TLV) (0.05 microg/m(3)). The median of median dust
      concentration ratios computed from the sampling heads at the fixed station
      decreased as follows: IOM (1.00) > Sierra (0.76) > 37-mm cassette (0.61) > MOUDI
      (0.48) > respirable (0.12). The same trends were observed with the ratios of the
      median of median Be concentrations at the fixed station but with a larger
      scattering within sampling heads as follows: IOM (1.00) > Sierra (0.69) > 37-mm
      cassette (0.64) > MOUDI (0.54) > respirable (0.19). The median of median ratios
      of dust (IOM (1.00) > Sierra (0.56) > 37-mm cassette (0.35) > respirable (0.06))
      and Be (IOM (1.00) > Sierra (0.66) > 37-mm cassette (0.48) > respirable (0.11))
      in dust were lower, and there was less scattering for the 37-mm cassette and SKC
      cyclone used during breathing zone sampling than for the same sampling heads at
      the fixed station. Inhalable aerosol measurements should remain the tool for
      estimating the risk of exposure to beryllium in these settings until a clear dose
      response is established for these sampling heads.

PMID- 19757294
TI  - Assessment of exposure to secondhand smoke at outdoor bars and family restaurants
      in Athens, Georgia, using salivary cotinine.
AB  - Exposure to secondhand smoke (SHS) in outdoor settings is a growing public health
      concern due to recent indoor smoking bans. The objective of this study was to
      measure salivary cotinine, a metabolite of nicotine, in subjects aged 21-30
      exposed to SHS outside bars and restaurants in Athens, Georgia. Nonsmokers
      participated during 6-hr periods in outdoor standing or seating areas of bars and
      restaurants where indoor smoking was banned, as well as a control outdoor
      location with no smokers over six weekends during the summer and early fall of
      2007. Pre- and post-exposure saliva samples (N = 25 person-days at the bar site,
      N = 28 person-days at the restaurant site, and N = 11 person-days at the control)
      were collected and analyzed for cotinine. The mean change in the response,
      (ln(post) - ln(pre)) salivary cotinine levels, was significantly impacted by the
      type of site (bar, restaurant, control) (F = 5.09; d.f. = 2, 6.7; p = 0.0455).
      The median percent increase in salivary cotinine from pre-test to post-test was
      estimated to be 162%, 102%, and 16% at the bar, restaurant, and control sites,
      respectively, values that were significant increases at bars (t = 4.63; d.f. =
      9.24; p = 0.0011) and restaurants (t = 4.33; d.f. = 4.47; p = 0.0097) but not at
      the control sites. On average, these pre-test to post-test increases in salivary
      cotinine were significantly higher at bar sites than control sites (t = 3.05;
      d.f. = 9.85; p = 0.0176) and at restaurant sites compared with control sites (t =
      2.35; d.f. = 5.09; p = 0.0461). Nonsmokers outside restaurants and bars in
      Athens, Georgia, have significantly elevated salivary cotinine levels indicative
      of secondhand smoke exposure.

PMID- 19757296
TI  - The influence of match location, quality of opposition, and match status on
      possession strategies in professional association football.
AB  - The aim of this study was to examine the effects of match location, quality of
      opposition, and match status on possession strategies in a professional Spanish
      football team. Twenty-seven matches from the 2005-2006 domestic league season
      were notated post-event using a computerized match analysis system. Matches were
      divided into episodes according to evolving match status. Linear regression
      analysis showed that possession of the ball was greater when losing than when
      winning (P < 0.01) or drawing (P < 0.05), and playing against strong opposition
      was associated with a decrease in time spent in possession (P < 0.01). In
      addition, weighted mean percentage time spent in different zones of the pitch
      (defensive third, middle third, attacking third) was influenced by match status
      (P < 0.01) and match location (P < 0.05). A combination of these variables and
      their interactions can be used to develop a model to predict future possession in
      football. The findings emphasize the need for match analysts and coaches to
      consider independent and interactive potential effects of match location, quality
      of opposition, and match status during assessments of technical and tactical
      components of football performance. In particular, the findings indicate that
      strategies in soccer are influenced by match variables and teams alter their
      playing style during the game accordingly.

PMID- 19757297
TI  - Neuromuscular fatigue induced by an isotonic heavy-resistance loading protocol in
      knee extensors.
AB  - The main aim of this study was to assess neuromuscular fatigue during a typical
      high-load, low-repetition loading protocol. Muscle stimulations were used to
      assess maximum voluntary contraction, resting single- and double-pulse twitch
      characteristics, and superimposed double-pulse twitch force (used to calculate
      voluntary activation) before and after an acute knee extension loading protocol.
      In our participants, who had previous resistance training experience, the mean
      voluntary activation level was 96.2% in an unfatigued state. Maximum voluntary
      contraction (-11.8%), resting double-pulse twitch force (-10.6%), and voluntary
      activation (-2.1%) were markedly decreased as a consequence of loading (P <
      0.05). In addition, although potentiated twitch characteristics were observed
      during the loading protocol, this was short-lived, as fatigue surpassed the
      potentiation mechanisms. Our results show that both central and peripheral
      mechanisms contributed to neuromuscular fatigue during the present loading
      protocol.

PMID- 19757300
TI  - Limited prognostic value of the International Prognostic Score in advanced stage
      human immunodeficiency virus infection-related Hodgkin lymphoma treated with the
      doxorubicin, bleomycin, vinblastine, and dacarbazine regimen.

PMID- 19757302
TI  - T-box-expressed-in-T-cells (T-bet) expression by the tumor cells of hairy-cell
      leukemia correlates with interferon-gamma production.
AB  - Hairy cell leukemia (HCL) is an uncommon B-cell malignancy with unknown
      pathogenesis. In an earlier study, we demonstrated that HCL cells highly express
      the transcription factor T-box-expressed-in-T-cells (T-bet). T-bet is the master
      regulator of the T-helper (Th)1 cell response regulating interferon gamma (IFN
      gamma) production and also plays a central role in the T-cell independent Th1
      like B-cell response. Here, we demonstrate by fluorescence activated cell sorting
      (FACS) analysis that neoplastic cells from the peripheral blood of five patients
      with HCL showed an enhanced expression of IFN-gamma after stimulation.
      Additionally, a comparison with 55 healthy individuals revealed a significant
      elevation of IFN-gamma in the sera of patients with HCL. Based on our recent
      findings that a non-neoplastic B-cell subset, the monocytoid B-cells, are T-bet
      positive and produce IFN-gamma, we propose that monocytoid and hairy B-cells have
      a similar function and that the T-bet-IFN-gamma axis is involved in the
      pathogenesis of HCL.

PMID- 19757304
TI  - Charting the path to the cure of chronic lymphocytic leukemia: consolidation
      strategies currently lead the way.

PMID- 19757306
TI  - Exploring mammalian target of rapamycin (mTOR) inhibition for treatment of mantle
      cell lymphoma and other hematologic malignancies.
AB  - The mammalian target of rapamycin (mTOR) pathway regulates translation of key
      proteins that contribute to the pathogenesis of advanced hematologic
      malignancies. Inhibitors of mTOR (temsirolimus, everolimus, and deforolimus)
      constitute a new class of antitumor agents, with potential for treatment of
      relapsed and/or refractory hematologic malignancies. Mantle cell lymphoma (MCL)
      was the first hematologic malignancy in which mTOR inhibition was explored as a
      treatment strategy, owing to its characteristic overexpression of cyclin D1, a G1
      cyclin regulated by mTOR signaling. Temsirolimus and everolimus exhibited
      antitumor activity against relapsed, refractory disease in phase II studies. In a
      randomized phase III trial, once-weekly intravenous temsirolimus 175 mg for 3
      weeks followed by 75 mg once weekly was recently shown to improve progression
      free survival (p=0.0009) and objective response rate (p=0.0019) versus
      investigator's choice of therapy in relapsed or refractory MCL. Evidence of
      antitumor activity seen in early clinical trials for other non-Hodgkin lymphoma
      subtypes, multiple myeloma, and myeloid leukemias supports further studies of
      mTOR inhibitors, alone or in combination strategies, in these diseases. Overall,
      the clinical findings to date strengthen mTOR inhibition as a novel and promising
      strategy for the treatment of certain hematologic malignancies, particularly for
      MCL.

PMID- 19757308
TI  - A new co-operative group: the European Myeloma Network Trialist Group.

PMID- 19757309
TI  - Dramatic resolution of respiratory symptoms with imatinib mesylate in patients
      with chronic myeloid leukemia presenting with lower airway symptoms resembling
      asthma.

PMID- 19757310
TI  - The Simplified Mantle-Cell Lymphoma International Prognostic Index predicts
      overall survival but not progression-free survival in patients with mantle-cell
      lymphoma treated with fludarabine and cyclophosphamide +/- rituximab: results of
      a randomized phase II trial.

PMID- 19757311
TI  - Protein kinase C-beta II expression in diffuse large B-cell lymphoma predicts for
      inferior outcome of anthracycline-based chemotherapy with and without rituximab.
AB  - Protein kinase C-beta II (PKC-beta II) expression has been reported to indicate
      inferior prognosis in diffuse large B-cell lymphoma (DLBCL) treated with
      anthracycline-based chemotherapy. This study compared prognostic significance of
      immunohistochemically determined PKC-beta II expression in de novo DLBCL treated
      with cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP)
      chemotherapy with and without rituximab. Outcomes were assessed in 80 consecutive
      patients, 48 treated with CHOP, and 32 with rituximab plus CHOP (R-CHOP). PKC
      beta II expression correlated with inferior overall survival (OS) and progression
      free survival (PFS) in CHOP-treated patients with low-risk International
      Prognostic Index (IPI) disease (0-2 adverse factors), but not in the overall
      patient group unstratified by IPI. PKC-beta II expression correlated with
      inferior OS and PFS in R-CHOP-treated patients unstratified by IPI status.
      Immunohistochemically demonstrated PKC-beta II expression thus identified patient
      subgroups where alternative treatment strategies may confer superior outcome. We
      now report that PKC-beta II expression has prognostic significance not only for
      CHOP therapy in low-risk IPI disease, but also for all patients receiving CHOP
      plus rituximab.

PMID- 19757314
TI  - Rituximab maintenance therapy in central nervous system lymphoma?

PMID- 19757315
TI  - A prospective study of left ventricle function after treatment with rapid
      infusion rituximab in patients with non-Hodgkin lymphoma.
AB  - We designed a prospective study to measure the left ventricular ejection fraction
      of 42 patients with non-Hodgkin lymphoma treated with Rituximab-based
      chemotherapy in a 1-h infusion. Our patients were not selected on the basis of
      their cardiac status. Cardiac history and other forms of co-morbidity were to be
      identified on entry. Before treatment, basal left ventricular ejection function
      (LVEF) was measured and every 6 months after treatment. Most patients were
      treated with CHOP-Rituximab combinations (79%). A drop in the post-treatment
      ejection fraction of over 10% from the pre-treatment base figure was found in 13
      patients (31% of the total of the series, 39% of those receiving adriamycin-based
      chemotherapy). None of the patients without adriamycin had a decrease in LVEF.
      Three patients with drop >10% recovered normally, but when LVEF decreased by over
      15%, which occurred in six patients (14.2%), none of them recovered normal level.
      Patients with normal systolic function had LVEF with a mean of 64.09 (+/-3.86)
      and patients with decreased systolic function had LVEF with a mean of 59.38 (+/
      5.43). Though the data in this study suggest that rapid-infusion Rituximab does
      not cause relevant cardiac toxicity, there was a high percentage of reductions in
      LVEF of over 10%.

PMID- 19757319
TI  - Inhibition of stromal cell-derived factor-1/CXCR4 axis for the cure of BCR-ABL
      positive chronic myeloid leukemia.

PMID- 19757320
TI  - "I remember", "I thought", "I know I didn't say": silence and memory in trauma
      narratives.
AB  - Society's interest in sexual abuse waxes and wanes in ways that mirror the
      fluidity of memory narrated by trauma survivors. Although a great deal of
      research explores memory processes, including the neurophysiology of trauma,
      little considers the ways in which disclosure delays and socio-cultural pressures
      for silence appear in narratives of childhood sexual abuse survivors. This
      qualitative study examines the narratives of four female survivors and
      illustrates the importance of listening with an ear towards the various layers of
      silence held within them. The analysis draws attention to the potential
      limitations of memory research, including the importance of considering
      relational aspects when examining trauma narratives.

PMID- 19757324
TI  - Effects of heat on camel platelet structure and function - a comparative study
      with humans.

PMID- 19757321
TI  - Localisation of endothelin B receptor variants to plasma membrane microdomains
      and its effects on downstream signalling.
AB  - The endothelin B (ET(B)) receptor can undergo a proteolytic cleavage resulting in
      an unglycosylated N-terminally truncated receptor. We investigated whether ET(B)
      receptor processing affects caveolar localisation and mitogenic signalling.
      Distinct subcellular localisations of ET(B) receptor constructs and epidermal
      growth factor (EGF) receptor ligands were analysed performing detergent-free
      caveolae preparations and total internal reflection fluorescence microscopy.
      ET(B) receptor-induced transactivation of the EGF receptor and its downstream
      signalling was investigated performing shedding assays and ERK1/2 phosphorylation
      analyses. In COS7 cells, the N-terminally truncated but not the full-length or
      glycosylation-deficient ET(B) receptor localised to caveolae. In caveolae-free
      HEK293 cells, only ET(B) receptor constructs fused to caveolin-2 localised to
      membrane microdomains. A caveolar accumulation of the ET(B) receptor disfavoured
      EGF receptor ligand shedding. Nonetheless, the activation of ERK1/2 was efficient
      and long-lasting. In HEK293 cells, the shedding activity was also impaired by N
      terminal truncation. The subsequent ERK1/2 phosphorylation was long-lasting only
      for the full-length ET(B) receptor. We conclude that the ET(B) receptor
      localisation might depend on the presence of caveolae within the cell
      investigated. The data further suggest that caveolar enrichment of ET(B)
      receptors does not facilitate the release of EGF receptor ligands. However,
      independent of their localisation, ET(B) receptors are able to induce an ERK1/2
      phosphorylation.

PMID- 19757328
TI  - Predictors of sustained therapeutic change.
AB  - The authors integrate explorations by Blatt and colleagues of contributions of
      patient personality, therapeutic relationship, and change in mental
      representation to sustained therapeutic change. A pretreatment personality
      characteristic, self-critical perfectionism, a negative self-schema,
      significantly interfered with therapeutic progress in manual-directed, brief
      outpatient treatment for depression. The therapeutic relationship, however,
      facilitated changes in this negative self-representation, leading to sustained
      therapeutic change. The authors also explored change in the content and
      structural organization of representations of self and significant others in long
      term, intensive inpatient treatment. A detailed clinical example elaborates the
      processes through which the therapeutic relationship facilitates changes in the
      thematic content and cognitive structural organization of patients' interpersonal
      schemas that appear to be the basis for sustained therapeutic gain.

PMID- 19757329
TI  - Expression of renal aquaporins is down-regulated in children with congenital
      hydronephrosis.
AB  - OBJECTIVE: This study investigated mRNA and protein expression of four renal
      aquaporin isoforms [AQP1, 2, 3 and 4 (AQP1-4)] in congenital hydronephrotic
      kidneys (HK) due to pelviureteral junction obstruction and normal control
      kidneys. MATERIAL AND METHODS: The expression of AQP1-4 was evaluated in 22
      children (15 boys, seven girls, aged 58.9+/-54.3 months) using semi-quantitative
      reverse transcriptase-polymerase chain reaction (RT-PCR) techniques,
      immunoblotting and immunohistochemistry. Hydronephrosis was graded by ultrasound
      according to the Society for Fetal Urology. RESULTS: Both RT-PCR and
      immunoblotting showed significantly reduced mRNA and protein expression of AQP1-4
      in grade IV compared with those in grade III HK and controls. Sequencing
      demonstrated 99% homology of AQP1-4 with those in GenBank. Positive
      immunoreactivity of AQP1 was found in plasma membranes of the proximal tubule,
      thin descending limb of Henle and descending vasa recta; AQP2 in the apical
      membrane of collecting duct principal cells; and AQP3 and 4 in the basolateral
      membrane of the same cells. In kidneys with grade IV hydronephrosis there was
      reduction in the protein abundance of all four AQP isoforms which was more
      pronounced compared with the protein abundance seen in kidneys with grade III
      hydronephrosis and control kidneys. CONCLUSION: The expression of AQP1-4 mRNA and
      protein abundance is reduced in proportion with the degree of hydronephrosis
      graded by ultrasound in human congenital HK.

PMID- 19757330
TI  - Role of echocardiography on the evaluation of patent ductus arteriosus in
      newborns.
AB  - The echocardiogram is the preferred procedure in confirming the diagnosis and
      characterizing PDA. Doppler echocardiography proved more efficient than clinical
      examination in grading PDA and becomes essential in the evaluation of clinically
      significant ductal shunting. Four patterns of PDA shunt can be identified using
      pulsed Doppler echocardiography: pulmonary hypertension, growing pattern,
      pulsatile pattern, closing pattern. In this review we confirm that
      echocardiography can provide a reasonable as well as accurate prediction of the
      development of later clinically significant PDA by a combination of variables
      that are easy to measure and compare.

PMID- 19757331
TI  - Alpha1-acid glycoprotein for the early diagnosis of neonatal sepsis.
AB  - OBJECTIVE: We aimed to evaluate the diagnostic value of C-reactive protein (CRP)
      and alpha1-acid glycoprotein (alpha1AG) in the early diagnosis of neonatal
      sepsis. DESIGN: The study was prospectively conducted among newborns hospitalized
      for 'rule out sepsis' to neonatal intensive care unit (NICU). SETTING AND
      SUBJECTS: A total of 97 children [16 with confirmed sepsis (Group I), 34 with
      clinical sepsis (Group II), and 47 in control group (Group III)] were enrolled in
      the study. On admission to NICU, blood was sampled for CRP, blood culture, and
      alpha1AG before starting antibiotherapy. Twenty-four hours later CRP and alpha1AG
      levels were detected for second tests in the study group. RESULTS: In Group I and
      II, while the 1st and 2nd tests CRP levels were not different, the 2nd test
      alpha1AG levels were significantly higher than the 1st test results (p<0.01).
      Second test CRP and alpha1AG levels were also statistically higher in Group I
      than Group II (p<0.05). CONCLUSION: It is shown that CRP has limited value in the
      early diagnosis of neonatal sepsis. A significant increase in alpha1AG levels was
      detected in neonatal sepsis but its high specificity was accompanied with low
      sensitivity. Since the 2nd test alpha1AG values resulted with high sensitivity,
      we suggest that serial alpha1AG tests may be used but a single test for alpha1AG
      has limited usefulness in the neonatal sepsis which requires rapid diagnosis.

PMID- 19757333
TI  - Neonatal asphyxia and forensic medicine.
AB  - In the last decades, the scientific literature addressing neonatal encephalopathy
      has grown in a logarithmic way and malpractice claims in obstetrics and
      neonatology have become a major threat to the health service. At the moment,
      scientific evidence are insufficient to clearly identify in each single case
      whether the hypoxic insult has developed in the course of labor or in the first
      few hours after the birth or, otherwise, whether the damage has to recognize a
      remote and long-lasting cause acting during pregnancy. Several authors feel that
      this scientific uncertainty leads to a higher percentage of civil suit decisions
      prone to recognizing a guilty medical behavior, and they wish a more in-depth
      analysis of all these cases to clearly identify all the data either in favor or
      in contrary to the assumption of the existence of a causal correlation between
      neonatal encephalopathy and medical misbehavior. This article will focus on the
      medico-legal approach to a hypoxic-ischemic event in the perinatal period,
      addressing the relevant data to be collected in order to establish the medical
      and juridical cause of the neonatal damage.

PMID- 19757334
TI  - Effects of acupressure at the Sanyinjiao point (SP6) on the process of active
      phase of labor in nulliparas women.
AB  - Introduction. The reduction of the duration and pain of the active phase of labor
      is a very important issue and therefore always under serious investigation.
      Objective. The purpose of the present study is to evaluate the effect of
      acupressure at the Sanyinjiao point (SP6) on the duration and pain of the active
      phase of labor in nulliparas women. Method. A single blind randomized clinical
      trial was performed on 120 eligible nulliparas women who were at the beginning of
      active phase of labor (3-4 cm dilatation of cervix plus proper uterine
      contractions). The women were randomly assigned into two groups. The case group
      (n = 60), received acupressure at Sanyinjiao point (above the ankle), for 30 min
      during contractions. In the control group (n = 60), simply a touch at this point
      without massage was performed. Two hours later a second pelvic examination was
      performed and in the absence of good forceful contractions oxytocin in the
      classical form was infused. Finally, duration of active phase, severity of pain
      (using the Visual Analogue Scale), the amount of necessary oxytocin and necessity
      to administer oxytocin and the route of delivery were compared between the two
      groups and statistical analyses were performed using SPSS 15. Results. The mean
      duration of active phase was shorter in the case group (252.37 +/- 108.50 min vs.
      441.38 +/- 155.88, p = 0.0001). Six patients (10%) in the case group and 25
      patients (41.7%) in the control group delivered via cesarean section (p =
      0.0001). The severity of pain in the case group was less than the control group
      (5.87 +/- 1.77 vs. 6.79 +/- 1.52, p = 0.003). Twenty-five women (41.7%) in the
      case group and 38 women (63.3%) in the control group needed oxytocin (p = 0.017)
      The amount of necessary oxytocin in the case group was less than the control
      group (73.33 +/- 97.19 ml vs. 126.6 +/- 97.19 ml, p = 0.003). Conclusion.
      Acupressure at Sanyinjiao point (SP6) reduced the duration and severity of pain
      of the active phase of labor, cesarean section rates, and necessity and amount of
      oxytocin.

PMID- 19757335
TI  - Neonatal morbidity and mortality of late-preterm babies.
AB  - OBJECTIVE: To analyze neonatal morbidity and mortality rates of late-preterms and
      to compare them with their term counterparts in a tertiary care unit in Turkey.
      STUDY DESIGN: The study included 252 late-preterm newborns (34 0/7--36 6/7 weeks'
      gestational age), admitted to Neonatal Intensive Care Unit in the first 24 h of
      life between January 2005 and June 2007 and 252 newborns born in the same
      hospital in the same period of time. Babies with major congenital and/or
      chromosomal abnormalities were excluded. RESULTS: The mortality rate was 2.3% in
      late-preterms. None of the term newborns died. Compared to terms, late-preterms
      were 11 times more likely to develop respiratory distress, 14 times more likely
      to have feeding problems, 11 times more likely to exhibit hypoglycemia, 3 times
      more likely to be readmitted and 2.5 times more likely to be rehospitalized. Late
      prematurity, being large for gestational age, male gender, and cesarean delivery
      were significant risk factors for respiratory distress. CONCLUSION: Late-preterms
      have significantly higher risk of morbidity and mortality compared with term
      newborns. Greater concern and attention is required for the care of this ignored,
      at-risk population.

PMID- 19757336
TI  - Late occurrence of severe hyponatremia followed by extrapontine osmotic
      demyelination syndrome after successful conservative management of postpartum
      hemorrhage due to placenta accreta by uterine artery embolization.
AB  - Development of severe hyponatremia followed by extrapontine osmotic demyelination
      syndrome was reported as a significant late complication after successful
      conservative management of postpartum hemorrhage due to placenta accreta by
      uterine artery embolization.

PMID- 19757337
TI  - The effects of vascular intrauterine growth retardation on cortical astrocytes.
AB  - OBJECTIVE: We sought to determine the pathogenesis of neurodevelopmental
      impairments in survivors of intrauterine growth retardation (IUGR). METHODS: We
      used an experimental rabbit vascular IUGR model. We ligated 25% of uteroplacental
      vessels (partial ischemia) of one-half of the fetuses on day 25 at the end of the
      third trimester. We then determined hemispheral DNA and protein levels, and used
      glial fibrillary acidic protein (GFAP) staining to count the labeled astrocytes
      at the superficial cortical layers. RESULTS: Ischemic fetuses were significantly
      smaller than control fetuses and presented a disproportionately small body and a
      relatively larger head compared with the normal body/head ratio, confirming the
      study model as that of asymmetric IUGR. Hemispheral DNA was unchanged in IUGR
      fetuses, but they had decreased brain weight, hemispheral protein content, and a
      reduced number of mature (GFAP-positive) cortical astrocytes compared with
      control fetuses. CONCLUSION: Vascular IUGR, as demonstrated in our asymmetric
      IUGR model, adversely affected brain growth, cell size, and cortical astrocytes
      maturation. In view of the neurotrophic and neuroprotective functions of
      astrocytes, a reduced number of mature astrocytes during this critical period of
      development may be implicated in the pathogenesis of the neurodevelopmental
      impairments observed in IUGR.

PMID- 19757338
TI  - Coagulation abnormalities and severe intraventricular hemorrhage in extremely low
      birth weight infants.
AB  - BACKGROUND: The association between intraventricular hemorrhage (IVH) and
      coagulation in infants has been a subject of controversy. Only few publications
      assessing risk factors for development of IVH reported results of coagulation
      studies. OBJECTIVES: To evaluate the levels of coagulation and fibrinolysis
      systems in ELBW infants and determine their influence on IVH. PATIENTS AND
      METHODS: Following IRB approval coagulation status of 38 ELBW infants was
      evaluated on first and second day of life. Severity of IVH assessed by cerebral
      ultrasonography was graded according to Papile classification. Newborns were
      assigned to either Group A--Grade III or IV, or Group B--Grade I-II, or no IVH.
      RESULTS: Neonates with Grade III/IV IVH had significantly lower plasma Factor VII
      (FVII) level on first day of life and FVII differed significantly between Groups
      A and B with sensitivity of 100%, specificity 41% for a cut-off value of< 7%. In
      Group A there was no improvement of prothrombin and activated partial
      thromboplastin times on Day 2. A significant decline of platelet count was also
      observed. CONCLUSIONS: High-grade IVH coincides with severe derangement of
      coagulation in ELBW infants with FVII level being the most sensitive, it is not
      clear what the reason for such low FVII concentration is. Further studies are
      indicated.

PMID- 19757339
TI  - [Advances in the surgery of metastases].

PMID- 19757340
TI  - [Liver metastases from neuroendocrine tumours of the gastroenteropancreatic
      system--therapeutic strategies].
AB  - Neuroendocrine tumours (NET) differ appreciably with regard to their biological
      behaviour from tumours of epithelial origin. In general this leads to a better 5
      year survival rate. Liver metastases per se and also in cases of NET result in a
      significantly poorer survival in comparison to tumours without metastases. In
      contrast to those with epithelial tumours, about (2/3) of the NET patients
      already have liver metastases at the time of diagnosis. Thus, in spite of the
      rarity of these tumours, the surgeon is frequently confronted with this tumour
      entity. Among other factors the prognosis depends on the primary localisation of
      the NET (pancreatic NET poorer than non-pancreatic NET) as well as the staging
      and grading (proliferation index Ki-67) of the tumours. In this article, we
      characterise the surgical and ablative therapies for liver metastases from NET of
      the gastrointestinal tract from both curative and palliative points of view on
      the basis of the recently published guidelines of the ENETS (European
      Neuroendocrine Tumour Society). Furthermore, the various options for conservative
      therapy are discussed and assessed for their relative values. For localised
      tumour disease, also of both liver lobes, the resection of liver metastases
      (single or multi-stage operation, if necessary in combination with RFA) remains
      the standard therapy. Liver resections as debulking operations (target: resection
      of > 90 % tumour volume) with good preoperative planning can also be carried out
      under palliative criteria. For diffuse liver metastases with more than 50 %
      tumour volume in the liver, orthotopic liver transplantation, if necessary even
      as a multivisceral transplantation, may be considered in individual cases. For
      inoperable metastases, depending on the tumour load in the liver, the tumour
      localisation (intrahepatic versus intra- and extrahepatic), the tumour grading
      (proliferation index Ki-67), the dynamics of tumour growth, and the primary
      localisation of the tumour, differentiated biotherapy with somatostatin
      analogues, peptide-mediated radioreceptor therapy (PRRT), transarterial
      chemoembolisation (TACE) and selective intraarterial radiotherapy (SIRT),
      chemotherapy and new molecular target-directed therapy options can be employed.
      The utilities of these treatment options are presented and discussed.

PMID- 19757341
TI  - [Current surgical management of pulmonary metastases].
AB  - Surgical resection has been the first choice for the treatment of isolated
      pulmonary metastases secondary to extrapulmonary malignancies. Despite recent
      advances, systemic chemotherapy for metastatic disease without the use of surgery
      is considered to be merely palliative, as there are rarely long-term survivors.
      Criteria for resection and prognostic parameters help facilitate patient
      selection. In addition to the established parameters the most significant factors
      in selecting patients for operation include the number of pulmonary metastases,
      disease-free interval, serum tumour marker level, and the question of mediastinal
      and hilar lymph node metastases. Complete surgical resection is critical to
      achieving long-term survival and is best accomplished via open thoracotomy
      accompanied by a systematic mediastinal and hilar lymph node dissection. The
      recent development of video-assisted thoracoscopic surgery (VATS) and advances in
      thoracic imaging technique has made the VATS approach more amenable for resection
      of small pulmonary nodules. However, the oncological radicality of VATS is
      questionable for pulmonary metastasectomy, thus the VATS approach is mostly
      limited to diagnostic purposes and in highly selected groups of patients with
      limited, peripherally located lesions. These operations should be performed
      preferably within a prospective study setting. All results together demonstrate
      that resection and re-resection of pulmonary metastases can be beneficial in
      patients, carefully selected by a multidisciplinary tumour board of thoracic
      surgeons and medical oncologists.

PMID- 19757342
TI  - [Timing of resection in patients with colorectal carcinoma and synchronous liver
      metastases].
AB  - Timing of surgical therapy in patients with synchronous colorectal liver
      metastases is becoming more complex. The standard therapy for most of the
      patients remains resection of the colorectal cancer first followed 6 weeks later
      by liver resection. Simultaneous colon and liver resection is safe and advisable
      in cases of minor liver resections and right-sided colon tumours. Major liver
      resections in combination with resection of the colorectal cancer carry the risk
      of increased postoperative morbidity and mortality. They should be considered for
      selected patients only. A pre-requisite is, in addition, special expertise of the
      operating surgeon in colorectal as well as in hepatobiliary surgery. If the
      synchronous liver metastases are near to essential anatomic structures, the liver
      resection should be performed before the bowel resection. The same holds if the
      metastases are technically resectable, but the future liver remnant seems to be
      too small. Using well known techniques, the future liver remnant should be
      increased and the liver metastases resected before treatment of the colonic
      primary tumour. The risk for local complications is very low when leaving the
      colorectal tumour in situ during treatment of liver metastases. When synchronous
      liver metastases are technically not resectable or carry a high risk of an R1
      resection, patients should be treated first with systemic neo-adjuvant
      chemotherapy. If sufficient down-sizing of the metastases can be achieved, liver
      resection should be performed before bowel resection. A close cooperation between
      the oncologist and the hepatobiliary surgeon is most important, since the window
      for curative surgery is rather limited in these patients. In patients with
      resectable synchronous liver metastases, the advantage of a neoadjuvant
      chemotherapy has not been proven yet.

PMID- 19757343
TI  - [Liver resection for non-colorectal, non-neuroendocrine liver metastases--is
      hepatic resection justified as part of the oncosurgical treatment?].
AB  - BACKGROUND: The value of hepatic resection for non-colorectal, non-neuroendocrine
      liver metastases remains controversial and is still under debate. Although there
      are numerous reported cases, the results are inconsistent due to the
      heterogeneity of the enrolled patients. The aim of the present study was to
      determine the utility of liver resection in the long-term outcome of patients
      with non-colorectal, non-neuroendocrine liver metastases and to define prognostic
      factors predicting long-term survivors. METHODS: The records of patients
      undergoing liver resection for non-colorectal, non-neuroendocrine liver
      metastases between January 1994 and December 2008 were analysed. Patient
      demographics, tumour characteristics, type of resection, long-term outcome and
      prognostic factors were analysed. RESULTS: Between 1994 and December 2008 273
      liver resections were performed in 242 patients because of non-colorectal, non
      neuroendocrine liver metastases. The morbidity rate was 20.9 % (n = 57), the
      mortality rate was 2.2 % (n = 6). Patient survival at 1, 3, 5 and 10 years was 76
      %, 42 %, 28 % and 13 %, respectively. In multivariate analyses margin status (R0
      vs. R2; p = 0.001) and time to metastases (synchronous vs. metachronous) were
      predictors of survival. Patient's age, type of resection, number and size of
      metastases did not achieve significance. According to the primary tumour site,
      patient survival differed. Patients with urological and gynaecological primary
      tumours fared better whereas patients with liver metastases from gastrointestinal
      primary tumours did worse without reaching statistical significance. CONCLUSION:
      Liver resection for non-colorectal, non-neuroendocrine liver metastases is safe
      and effective. For individual patients with controlled systemic disease, liver
      resection can offer appropriate survival rates and should be a part of the onco
      surgical treatment.

PMID- 19757344
TI  - [Surgical technique and postoperative morbidity following radical
      inguinal/iliacal lymph node dissection--a prospective study in 67 patients with
      malignant melanoma metastatic to the groin].
AB  - BACKGROUND: The surgical radical inguinal / iliacal lymph node dissection (RLND)
      is the procedure of choice in patients presenting with lymphatic metastasis of
      melanoma of the lower extremity or the lower part of the trunk. The perioperative
      morbidity of patients includes not only local wound complications, seroma
      formation or lymphatic fistula but also leg oedema, deep venous thrombosis and
      neuralgic disorders postoperatively. The aim of this prospective study was the
      evaluation of postoperative morbidity in patients undergoing radical
      inguinal/iliacal RLND in a standardised surgical fashion. PATIENTS AND METHODS:
      67 patients suffering from malignant melanoma of the lower extremity or the lower
      trunk with metastatic lymph nodes in the groin or the iliacal region underwent a
      combined RLND of the inguinal / iliacal region or the groin alone between 2003
      and 2006. All operations were performed in a standardised technique. The main
      criterion of the study was the incidence of postoperative wound complications.
      Minor endpoints included the incidence of lymphatic fistula, the length of
      hospital stay, and the development of temporary or permanent leg oedema. RESULTS:
      64 patients underwent inguinal / iliacal and 3 patients only inguinal LND (lymph
      node dissection). All patients tolerated the procedure well. The overall wound
      complication rate was 34 %. One patient died on the 21st postoperative day due to
      a pulmonary embolism and a simultaneous cerebral apoplexy. Lymphatic fistula
      occurred in 22 (33 %) patients whereas seroma resulted in 23 (34 %) patients. The
      length of hospital stay was 15 (3-41) days. A relevant leg oedema was observed in
      9 (13 %) patients. CONCLUSION: Even with a proper perioperative management and a
      precise wound care management, one-third of the patients undergoing radical
      inguinal / iliacal lymphadenectomy suffer from a complication requiring medical
      or interventional treatment. Our data demonstrate that most of these
      complications can be treated sufficiently by conservative treatment. A fitted
      surgical support hose could prevent long-term complications.

PMID- 19757345
TI  - [Practical neoadjuvant and adjuvant therapies for rectal cancer. How many
      patients are actually recruited in multimodality therapy concepts? An analysis of
      the Tumour Centre Schwerin].
AB  - INTRODUCTION: For rectal cancer in UICC stage II or III, a neoadjuvant
      chemoradiotherapy or short-course radiotherapy is established to reduce the
      incidence of local relapses. It has been documented that the neoadjuvant therapy
      is superior to the adjuvant therapy. In spite of the formulation of therapeutic
      principles in guidelines, they are not consistently applied. The actual rate of
      application and the reasons for a change from the recommended treatment strategy
      have been investigated. MATERIAL AND METHOD: The data of the tumour centre West
      Mecklenburg were analysed. Data concerning the type and stage of rectal cancer,
      multimodal treatment (surgery with or without neoadjuvant therapy or adjuvant
      therapy) and treatment according to the level of medical care of hospitals were
      recorded from 2000 to 2008. In addition, in our clinic prospectively collected
      data of patients with rectal cancer (September 2006 until December 2008) were
      used to find out the reasons for the denial of neoadjuvant therapy. RESULTS:
      During the observation period we detected 348 patients with rectal cancer in UICC
      stage II or III in the area of the tumour centre West Mecklenburg. 16 % of these
      patients were treated pre-operatively. An increase in the preoperative multimodal
      treatment from 3 % to 39 % was observed. Hospitals with higher provisions of
      medical care applied the multimodal treatment 4-fold more frequently during this
      period of time. 55 patients of our own clinic were found to be of UICC stage II
      or III. 6 patients were emergency cases. The carcinoma was found in the lower or
      middle third of the rectum in 38 of our patients. The endosonographical
      examination could not adequately show the tumour or was falsely negative in 16 of
      these patients. A neoadjuvant treatment was started for 58 % of the patients.
      Overall, 76 of patients with rectal carcinoma were treated adjuvant or
      neoadjuvant, 62 of them with a complete treatment scheme. DISCUSSION: The
      application of neoadjuvant treatment for rectal carcinoma in UICC stage II or III
      in West Mecklenburg was unexpectedly low during the observation period. However,
      an increase in treatment frequency was detected. During the same period of time
      the number of patients treated in hospitals of basic and standard medical care
      decreased by half. This is the reason for the regional increase of neoadjuvant
      treatment. 47 % of the patients of our clinic received neoadjuvant
      chemoradiotherapy or a short-course radiotherapy. Including the adjuvant
      treatment, 76 % of all patients were treated multimodally. An increase in
      neoadjuvant treatment can only be achieved by shifting patients to centres with
      an appropriate diagnostic facility and a regular tumour board for rectal cancer.

PMID- 19757346
TI  - [Clinical and pathological prognostic factors for cancers of the esophagogastric
      junction].
AB  - INTRODUCTION: Adenocarcinoma of the esophagogastric junction (AEG) is a
      particular tumour entity because two substantially different surgical procedures
      are required according to the location. There is no difference in long-term
      prognosis between the tumour types in spite of the different surgical procedures.
      We were interested to evaluate the clinical and pathological prognostic factors
      of the AEGs which were operated in our department. PATIENTS AND METHODS: 108
      patients were operated for AEG between 1.1.2000 and 1.4.2006 in our institution.
      32 (29.6 %) patients with distal esophageal cancer (type I according to Siewert)
      underwent a transthoracic esophagectomy with gastric pull-up and two-field
      lymphadenectomy. 57 (52.8 %) patients with type II and 19 (17.6 %) patients with
      type III cancers received an extended gastrectomy with D2 lymphadenectomy. The
      retrospective analysis was focused on clinical and pathological parameters.
      Possible differences between the tumour types were also evaluated. Median follow
      up was 11.4 months (range: 1-57 months). RESULTS: Follow-up data were complete
      for 107 patients. A median survival of 17.4 +/- 3.25 months and a cumulative
      survival of 30 % were independent of the tumour location and the surgical
      procedure. Overall hospital mortality was 3.7 %. The univariate analysis showed
      that survival was significantly associated with the T category, lymph node
      status, lymphangio- and angioinvasion and tumour grading. In the multivariate
      analysis, only lymph node status was identified as an independent prognosis
      factor for survival. Where-as the R status was not a prognostic factor per se,
      how-ever, patients with an R0 situation without lymphangio- and angioinvasion had
      a significantly better survival compared to all other patients (p = 0.001). An
      increased angioinvasion rate was observed in type III tumours (52.6 %) in
      comparison to type I (21.9 %) and type II (21.1 %) tumours. CONCLUSION: The
      prognostic factors of our patients determined substantially the prognosis of the
      patients. Patients with lymph- or haemangioinvasion should regarded as high-risk
      patients independent of the R status. Close oncological follow-up including
      potential adjuvant treatment in these patients is recommended.

PMID- 19757347
TI  - [Surgical management of bevacizumab-associated peritonitis due to perforation].
AB  - INTRODUCTION: Bevacizumab (Avastin, Fa. Roche, Genentech) is the first anti
      angiogenic agent to be approved for the routine clinical treatment of cancer. Its
      toxicity profile is different to that of standard chemotherapeutic substances.
      Despite the rarity of gastrointestinal (GI) perforation in patients treated with
      bevacizumab, this serious adverse event results in significant morbidity and
      mortality. It was the aim of this study, based on exemplary cases of the
      reporting clinic as well as on published experiences, to characterise the
      specific clinical findings, the extraordinary pathogenesis, and the therapeutic
      outcome of such cases of peritonitis caused by perforation after antibody
      treatment. METHODS: Data of all patients with perforation-caused peritonitis due
      to bevacizumab therapy since its clinical inauguration were sought in i) the
      database of the reporting clinic (case series), ii) in the published literature
      for comparison (historical comparative group) and iii) analysed with regard to
      results of the surgical management (evaluated parameters: rate of anastomotic
      insufficiency / disturbances of wound healing, morbidity, mortality). RESULTS:
      Over a time period of 4 years (from 2 / 1 / 2004 to 1 / 31 / 2008), overall 15
      patients were found in this study, among whom 4 patients came from the reporting
      clinic (mean age, 57 years; males : females = 2 : 2). The mean duration of
      antibody (Ab) treatment until occurrence of the complication was 70 days (range:
      8-150 days). Thirteen patients underwent surgical intervention, 2 patients died
      due to severe peritonitis without any operation. The overall morbidity was 73.3 %
      (n = 11 / 15), the mortality was 33.3 % (n = 5 / 15). All patients with an
      anastomosis developed an anastomotic insufficiency (100 %). Wound healing
      complications occurred in 38.5 % of the subjects (n = 5 / 13). CONCLUSIONS:
      Peritonitis after GI perforation due to bevacizumab-based Ab treatment needs to
      be considered as a rare but serious and life-threatening complication. Impairment
      of wound healing because of the inhibition of angiogenesis is the reason for a
      different management of GI perforation under these conditions compared with the
      standard surgical treatment of peritonitis of other causes. In particular, it is
      recommended to avoid primary anastomosis and to prefer application of an
      intestinal stoma.

PMID- 19757348
TI  - [The interdisciplinary treatment of Merkel cell carcinoma: a retrospective case
      analysis and review of the current literature].
AB  - BACKGROUND: Merkel cell carcinoma is a rare, -aggressive, neuroendocrine
      malignancy of the skin. Over the period from June 2005 to January 2007 (18
      months) 7 Merkel cell carcinomas in different tumour stages and localisations
      were treated in our department for hand, plastic and reconstructive surgery.
      Given an incidence rate of approximately 0.1-0.4 per 100 000 inhabitants, this
      accumulation of cases is considerably higher than would be statistically
      expected. This led us to analyse our cases retrospectively and provided the
      opportunity to discuss the treatment modalities on the basis of the current
      literature. PATIENTS AND METHODS: All patients were referred to our clinic after
      incomplete tumour excision and histopathological diagnosis elsewhere, for further
      surgical treatment. Two female and 5 male patients, aged 63 to 83 years, were
      treated. The patients' data were collected and analysed retrospectively. RESULTS:
      In all cases an R0 resection could be achieved, with safety resection margins
      between 1.5 cm and 4.5 cm. The reconstruction of the resulting defects was
      achieved by skin transplants in six cases and a primary suture in one case. All
      patients received adjuvant radiotherapy. Furthermore, three patients received
      adjuvant chemotherapy due to metastases of the progressed Merkel cell carcinoma.
      Three patients remained free of recurrence and in two patients a progression of
      the tumour disease could be impeded, whilst two patients succumbed to their
      disease. CONCLUSIONS: In the case of an early diagnosis, an R0 resection can
      usually be achieved. A safety resection margin of a minimum of 1.5 cm in the face
      and 3 cm for localisation on the extremities should be obtained. To reduce the
      local recurrence rate, adjuvant radiotherapy should be conducted. The benefit
      from chemotherapy still remains unclear.

PMID- 19757349
TI  - [Alveolar adenoma--a rare pulmonary mass: case report and review of the
      literature].
AB  - This report describes the case of a 58-year-old man presenting with haemoptysis.
      Chest X-ray and CT scans showed a solitary pulmonary mass in the right lower lobe
      without radiographic signs of malignancy. Definitive histology following
      thoracoscopic wedge resection showed the distinctive findings of an alveolar
      adenoma, a very rare benign tumour of the lung of unknown histogenesis. Its
      existence was first described in 1986 with less than 30 cases published to this
      day. Alveolar adenoma usually presents as a peripheral solitary lesion in
      asymptomatic, older patients. Its histological features, the benign proliferation
      of alveolar epithelium and septal mesenchyme, allow for its distinction from
      other benign lesions of the lung. Complete excision is considered curative on the
      basis of current knowledge.

PMID- 19757350
TI  - [Metastasis of an esophageal carcinoma at a PEG site--case report and review of
      the literature].
AB  - We describe the case of a 54-year-old man with a tumour of the proximal esophagus
      (cT3-4,N1,M0), who underwent percutaneous endoscopic gastrostomy (PEG) for
      enteral feeding. Primary radiochemotherapy was initiated shortly after PEG
      insertion. Five months after PEG insertion the patient detected a nodule at the
      site. The general practitioner diagnosed this nodule as a brotic reaction.
      Another six weeks later, ulceration that had grown along the PEG probe at the PEG
      site was observed on gastroscopy. The primary tumour was not visible.
      Histological examination showed an abdominal wall metastasis of the esophageal
      cancer. Despite subtotal gastrectomy with en-bloc resection of the tumour,
      distant metastasis developed. The patient died six months after surgery. About 47
      cases of abdominal wall metastases as late complications at the site have been
      reported until now. The mechanism of tumour spread of PEG site is a subject of
      controversial discussion. As direct mechanical tumour implantation is the most
      likely mechanism, an alternative method like operative (laparoscopic) or
      radiological PEG placement should be considered in cases with advanced, stenotic
      tumours.

PMID- 19757351
TI  - [Multiple carcinoids in the midgut causing intestinal gangrene--a case report].
AB  - CASE REPORT: We report the case of multiple midgut carcinoids causing segmental
      intestinal ischaemia in a 77-year-old man. He was admitted to our hospital
      because of a 2-month history of postprandial abdominal pain with nausea /
      vomiting and anaemia. The extensive diagnostic examinations (blood tests,
      ultrasound, computed tomography, hydro magnetic resonance) did not reveal any
      pathological findings. The small-bowel capsule endoscopy demonstrated multiple
      areas of bleeding. A laparotomy showed a local ischaemia of the small bowel, a
      segmental resection of the jejunum / ileum was performed. There were no signs of
      occlusion of the mesenteric artery. The pathological examination revealed 8
      carcinoids of the midgut (jejunum / ileum). Immune histology demonstrated
      serotonin-synaptophysin-chromogranin-producing carcinoids. The patient was re
      operated because of suspected ongoing mesenteric ischaemia, but no further
      pathologies were found. The postoperative course was uneventful. A subsequent
      octreotide scan was negative for metastases. DISCUSSION: Carcinoids may become
      symptomatic mimicking intestinal ischaemia. Although this coincidence is
      considered to be typical, it is still a rare event. The diagnosis is often
      delayed. EVS ("elastic vascular sclerosis") of the mesenteric artery is
      pathognomonic for these carcinoids but, as our case demonstrates, not mandatory.
      According to the literature, the stage of the disease corresponds to the extent
      of the intestinal ischaemia.

PMID- 19757352
TI  - [Evidence-based diagnostic approach to inherited retinal dystrophies 2009].
AB  - BACKGROUND: Hereditary retinal dystrophies comprise a heterogeneous group of
      inherited retinal disorders with variable clinical presentation and multiple
      associated genes. Clinical diagnosis and differential diagnosis are difficult.
      The purpose of the current paper is to provide guidelines for an effective
      diagnostic approach. METHODS: A literature search was carried out and our own
      data on clinical (n = 3200) and molecular genetic (n = 4050) diagnosis of
      patients with retinal dystrophies were evaluated. RESULTS: For an early diagnosis
      it is of importance to include inherited retinal dystrophies in the differential
      diagnosis of unexplained visual disturbances. The most important clinical test is
      the full-field electroretinogram (ERG), which allows detection or exclusion of
      generalised retinal dystrophies. If the full-field ERG is normal, a multifocal
      ERG will distinguish macular dystrophies. Fundus autofluorescence, near-infrared
      autofluorescence and high resolution optical coherence tomography improve the
      early diagnosis because morphological alterations can be detected prior to their
      ophthalmoscopic visibility. In addition, these non-invasive imaging techniques
      reveal new phenomena which are important for the differential diagnosis and
      follow-up of retinal dystrophies as well as for an improved understanding of
      their pathogenesis. Routine molecular genetic diagnosis is available for an
      increasing number of retinal dystrophies. A succinct clinical diagnosis is a
      prerequisite to allow selection of the gene(s) to be analysed. If genetic testing
      is indicated, a human geneticist should be involved for counselling of the
      patient and possibly further family members and initiation of the necessary steps
      for DNA testing. CONCLUSION: The combination of electrophysiological testing,
      retinal imaging and molecular genetic analysis allows a differentiated diagnosis
      of inherited retinal dystrophies and an individual counselling of patients. If
      inherited retinal dystrophies are suspected, a detailed examination in a retinal
      centre specialised on inherited retinal dystrophies is recommended.

PMID- 19757353
TI  - [Surgical treatment of diabetic macular oedema].
AB  - The therapy for diabetic macular oedema often remains unsatisfactory for both
      patient and treating physician. Therapeutic approaches comprise laser therapy as
      the evidence-based "basic therapy" and increasingly also intravitreal injections
      of drugs which, however, have only a limited effect. One argument for the use of
      vitrectomy in the treatment of diabetic macular oedema is its potentially
      permanent positive effect. On the one hand, removal of the adherent vitreous may
      facilitate the supply of the inner retina "per diffusionem" from the vitreous, on
      the other hand it may allow movement of harmful cytokines from the retina into
      the vitreous also by diffusion. Furthermore, from the pathophysiological
      standpoint, the vitreoretinal interface itself is modified by glycosylation
      processes and may thereby contribute to the occurrence of macular oedema.
      Pathological vitreofoveolar adhesions, which now can be visualised by use of
      ocular coherence tomography, may also add to the development of macular oedema in
      a mechanical-tractive manner. A critical analysis of the published clinical
      studies reveals that the macular retinal thickness is indeed reduced after
      vitrectomy, disappointingly however, this does not translate into better visual
      acuity in patients without detectable tractive components. But, in the case of
      eyes with tractive components of the diabetic macular oedema, there is good
      evidence for a surgical approach.

PMID- 19757354
TI  - [Comparative investigation of treatments for evaporative dry eye].
AB  - BACKGROUND: Evaporative dry eye is the most common form of tear film dysfunction.
      The present trial aims to evaluate the efficacy of two established treatment
      options with different modes of action by comparison. PATIENTS/MATERIAL AND
      METHODS: 216 patients suffering from evaporative dry eye were included in this
      prospective, randomised two-centre trial. Divided into two treatment groups,
      patients either received treatment with hyaluronate artificial tears (Vismed
      light) or a phospholipid-liposome eye spray (Tears Again), each for three months.
      Tests (lid-parallel conjunctival folds [LIPCOF], non-invasive break-up time
      [NIBUT], Schirmer's test, inspection of lids and subjective assessment) were
      performed before as well as 4 and 12 weeks after initiation of this study.
      RESULTS: In the patients of the eye spray group there was a significantly greater
      reduction of the LIPCOF grade (p < 0.02) and the grade of inflammation of the lid
      margin (p < 0.002). With respect to the tear film break-up time (NIBUT) there was
      a significant difference between the results of both groups (p < 0.003). The
      improvement of the break-up time in patients of the eye spray group turned out to
      be more than twice as high as that in the artificial tears group. CONCLUSIONS:
      Both therapies improved evaporative dry eye, but patients on phospholipid
      liposomal eye spray demonstrated greater clinical benefit from their therapy,
      particularly regarding the degree of inflammation of the lid margins as well as
      the grade of LIPCOF. When compared to hyaluronate artificial tears, NIBUT more
      than doubled in the phospholipid-liposome eye spray group. Clinical severity of
      dry eye is more pronounced when evaporative dry eye and aqueous tear deficiency
      coincide. A combination of the phospholipid-liposome eye spray and artificial
      tears appears to represent a considerable advancement in tear replacement therapy
      for severe cases of dry eye.

PMID- 19757355
TI  - [Bilateral modified Hummelsheim procedure in severe bilateral abduction
      deficiency].
AB  - BACKGROUND: Bilateral sixth nerve paralysis is a rare motility disturbance. The
      functional and cosmetic problems, operative management and postoperative outcome
      in three patients are presented. MATERIAL AND METHODS: We report on the pre- and
      postoperative findings of three patients who in one operative session received
      bilateral transposition surgery in modification of the Hummelsheim procedure.
      RESULTS: All three patients postoperatively showed good cosmetic results with no
      significant head posture for far and near fixation. The abduction deficiency was
      reduced. In one case a field of binocular single vision at far fixation was
      established. This field was positioned centrally and measured 15 degrees in
      diameter. No intraoperative or postoperative complications occurred. CONCLUSION:
      Simultaneous bilateral transposition surgery as a modified Hummelsheim procedure
      can reduce head turn in patients with severe bilateral abduction deficiencies and
      may reestablish limited binocular single vision. In regard to their psycho-social
      interactions, the patients benefit from the diminished angle of squint.

PMID- 19757356
TI  - [Surgical treatment modalities in uveal melanomas].
AB  - The treatment of large uveal melanomas poses a therapeutic challenge, due to the
      expected treatment-related side-effects. After sole radiotherapy the majority of
      patients are faced with radiogenic complications secondary to the large amount of
      tumour necrosis. Alternative treatment modalities addressing this issue are
      transscleral resection in arterial hypotension in anteriorly located tumours and
      endoresection via pars plana vitrectomy in posteriorly located tumours. A
      surgical resection treatment was applied in 292 patients with large uveal
      melanomas. In 150 patients the tumour was treated by transscleral resection and
      postoperative adjuvant (106)ruthenium brachytherapy and 142 patients were treated
      by primary proton beam irradiation and secondary endoresection. The mean follow
      up time was 3.8 and 2.5 years, respectively. Local tumour control was achieved in
      76 % and 98 %, respectively. The 5-year metastatic rates were 28 % and 21 % and
      eye retention was achieved in 82 % and 97 %, respectively. Surgical resection of
      uveal melanomas with adjuvant radiotherapy is the treatment of choice in cases of
      large tumours, avoiding enucleation in the vast majority of cases in the long
      term, without increasing the incidence of tumour-related risks.

PMID- 19757357
TI  - Chromatographic fingerprint investigation for quality evaluation and control of
      Shengui hair-growth tincture.
AB  - The quality assessment and control of traditional Chinese medicines (TCM) has
      received a great deal of attention worldwide with its tremendous increasing use.
      Chromatographic fingerprinting is thought to be a good approach for this task and
      has been used for the quality assessment and control of many herbal medicines.
      However, there are only a few reports on the quality control of TCM preparation
      by chromatographic fingerprinting. In the present work, gas chromatography-mass
      spectrometry (GC-MS) combined with chemometric methods were used for the
      chromatographic fingerprint analysis and characterization of Shengui hair-growth
      tincture (SGHGT), which is a complex TCM prescription made from 9 herbs. Thirteen
      "common peaks" were identified by MS and a comparison of retention indices. The
      software "The Traditional Chinese Medicine Quality Control System 1.0" (TCMQCS,
      developed by Research Center of Modernization of Chinese Herbal Medicine, Central
      South University) was used to evaluate the similarities. Principal component
      analysis (PCA) was used for the classification of 23 batches of SGHGT samples
      provided by Hunan Fusheng Hairgrowth Pharmaceutical Factory. The 23 batches of
      samples made in different years had similar GC-MS fingerprints. Four clusters
      were obtained from PCA treatment according to their production year. The proposed
      method was validated in precision and repeatability through the calculation of
      relative retention times and relative peak areas of the 13 common compounds to
      the reference compound eugenol. The result indicated that the method is feasible
      and applicable for the quality control of SGHGT. SUPPORTING INFORMATION available
      online at http://www.thieme-connect.de/ejournals/toc/plantamedica.

PMID- 19757358
TI  - Prospective comparison of radial and linear endoscopic ultrasound for diagnosis
      of chronic pancreatitis.
AB  - BACKGROUND AND STUDY AIMS: Linear endoscopic ultrasonography (EUS) is currently
      favored by many endosonographers for the evaluation of pancreatic pathology.
      However, radial EUS was used in early studies validating EUS for chronic
      pancreatitis. Radial and linear EUS have never been compared for the diagnosis of
      chronic pancreatitis. The aim of this study was to compare radial and linear EUS
      for the diagnosis of chronic pancreatitis using the secretin-stimulated
      endoscopic pancreatic function test (ePFT) as the reference standard. PATIENTS
      AND METHODS: One hundred consecutive patients evaluated for pain of possible
      pancreatic origin underwent combined radial EUS, linear EUS, and secretin ePFT
      during a single endoscopic session. EUS images were acquired on videotape and
      blindly scored by three reviewers. The main outcome measure was diagnostic
      accuracy. RESULTS: The accuracy of radial EUS and linear EUS (cutpoint > or = 4
      criteria) was 84 % and 74 %, respectively. The statistical test for
      noninferiority was significant ( P < 0.001) suggesting that the accuracy of
      radial EUS is as good as or superior to linear EUS. The ratio of accuracy (pi
      (radial)/pi (linear)) was 1.14 (95 % confidence interval [CI] 0.99 to 1.28). No
      statistically significant differences were found between radial and linear EUS in
      terms of sensitivity, specificity, or overall discriminative ability (area under
      receiver operating characteristic curve 0.84 vs. 0.76, P = 0.10). Interobserver
      variability was similar for radial (Fleiss' kappa = 0.61, 95 %CI 0.43 to 0.79)
      and linear EUS (kappa = 0.50, 95 %CI 0.28 to 0.72). CONCLUSIONS: The accuracy of
      radial EUS is as good as linear EUS for the diagnosis of chronic pancreatitis.

PMID- 19757359
TI  - An unusual presentation of herpes simplex esophagitis: a nonhealing "peptic"
      ulcer.

PMID- 19757360
TI  - Symptomatic esophageal stricture and buried metaplasia after radiofrequency
      ablation of Barrett's esophagus.

PMID- 19757361
TI  - Multiple hemorrhagic duodenal ulcers caused by cytomegalovirus infection.

PMID- 19757362
TI  - End-organ ischemia as an unforeseen complication of endoscopic-ultrasound-guided
      celiac plexus neurolysis.

PMID- 19757363
TI  - A case of gastric carcinosarcoma.

PMID- 19757364
TI  - Appendiceal mucocele presenting with lower abdominal pain.

PMID- 19757365
TI  - Successful endoscopic treatment of spontaneous perforation of the common hepatic
      duct.

PMID- 19757366
TI  - Anisakiasis and vanishing tumor of the cecum.

PMID- 19757367
TI  - Splenic rupture as a complication of endoscopic esophageal bouginage.

PMID- 19757368
TI  - Identification and treatment of a duodenal diverticular hemorrhage: an
      illustration of the usefulness of the jumbo-channel therapeutic endoscope.

PMID- 19757369
TI  - Epithelioid angiosarcoma in the duodenal bulb.

PMID- 19757370
TI  - A first report of collagenous gastritis, sprue, and colitis in a 9-month-old
      infant: 14 years of clinical, endoscopic, and histologic follow-up.

PMID- 19757371
TI  - A case of colonic mantle cell lymphoma: new insights in a rare disease.

PMID- 19757372
TI  - Endoscopic therapy using novel fan devices.

PMID- 19757373
TI  - A new device for endoscopic submucosal dissection of a submucosal
      gastrointestinal stromal tumor.

PMID- 19757374
TI  - Successful bronchial artery embolization for refractory esophageal bleeding after
      failed endoscopic therapy.

PMID- 19757375
TI  - Life-threatening hemorrhage following large-balloon endoscopic papillary dilation
      successfully treated with angiographic embolization.

PMID- 19757376
TI  - [Promoting instead of controlling health--lessons learned, lessons to learn].
AB  - Health promotion, as laid down in the Ottawa Charta by the World Health
      Organisation, embraces the call for self-responsibility. Self-responsibility,
      however, is not merely directed towards apparently personal risk factors. The
      Ottawa Charta clearly puts health in a wider societal context and follows the
      line of early social medicine, which, as Virchow put it, understood politics as
      medicine on a large scale. With the increasing dominance of neoliberal thinking
      during the 1990s, this view of health in its societal context was pushed aside to
      make way for an individualistic understanding of self-responsibility. At the same
      time a resurgence of expert-led prevention strategies could be observed.
      Recently, however, the discussion on self-responsibility appears to be regaining
      societal aspects. The task on hand is, to support this societal approach to
      health whilst at the same time to ensure the field of health promotion does not
      overstretch itself.

PMID- 19757377
TI  - Pdx1-transfected adipose tissue-derived stem cells differentiate into insulin
      producing cells in vivo and reduce hyperglycemia in diabetic mice.
AB  - Insulin-dependent diabetes mellitus (IDDM) is characterized by the rapid
      development of potentially severe metabolic abnormalities resulting from insulin
      deficiency. The transplantation of insulin-producing cells is a promising
      approach for the treatment of IDDM. The transcription factor pancreatic duodenal
      homeobox 1 (Pdx1) plays an important role in the differentiation of pancreatic
      beta cells. In this study, the human Pdx1 gene was transduced and expressed in
      murine adipose tissue-derived stem cells (ASCs). To evaluate pancreatic repair,
      we used a mouse model of pancreatic damage resulting in hyperglycemia, which
      involves injection of mice with streptozotocin (STZ). STZ-treated mice
      transplanted with Pdx1-transduced ASCs (Pdx1-ASCs) showed significantly decreased
      blood glucose levels and increased survival, when compared with control mice.
      While stable expression of Pdx1 in ASCs did not induce the pancreatic phenotype
      in vitro in our experiment, the transplanted stem cells became engrafted in the
      pancreas, wherein they expressed insulin and C-peptide, which is a marker of
      insulin-producing cells. These results suggest that Pdx1-ASCs are stably
      engrafted in the pancreas, acquire a functional beta-cell phenotype, and
      partially restore pancreatic function in vivo. The ease and safety associated
      with extirpating high numbers of cells from adipose tissues support the
      applicability of this system to developing a new cell therapy for IDDM.

PMID- 19757378
TI  - Modeling and quantification of cancer cell invasion through collagen type I
      matrices.
AB  - Tumor invasion is the outcome of a complex interplay between cancer cells and the
      stromal environment. Considering the contribution of the stromal environment, we
      developed a membrane-free single-cell and spheroid based complementary model to
      study cancer invasion through native collagen type-I matrices. Cell morphology is
      preserved during the assays allowing real time monitoring of invasion-induced
      changes in cell structure and F-actin organization. Combining these models with
      computerized quantification permits the calculation of highly reproducible and
      operator-independent data. These assays are versatile in the use of fluorescent
      probes and have a flexible kinetic endpoint. Once the optimal experimental
      conditions are empirically determined, the collagen type-I invasion assays can be
      used for preclinical validation of small-molecule inhibitors targeting invasion.
      Initiation and monitoring of the single-cell and spheroid invasion model can be
      achieved in 8 h (over 3 days) and in 14 h (over 8 days) respectively.

PMID- 19757379
TI  - Insulin-like growth factor-2 regulates early neural and cardiovascular system
      development in zebrafish embryos.
AB  - The insulin-like growth factor (IGF) family is essential for normal embryonic
      growth and development and it is highly conserved through vertebrate evolution.
      However, the roles that the individual members of the IGF family play in
      embryonic development have not been fully elucidated. This study focuses on the
      role of IGF-2 in zebrafish embryonic development. Two igf-2 genes, igf-2a and igf
      2b, are present in the zebrafish genome. Antisense morpholinos were designed to
      knock down both igf-2 genes. The neural and cardiovascular defects in IGF-2
      morphant embryos were then examined further using wholemount in situ
      hybridisation, TUNEL analysis and O-dianisidine staining. Knockdown of igf-2a or
      igf-2b resulted in ventralised embryos with reduced growth, reduced eyes,
      disrupted brain structures and a disrupted cardiovascular system, with igf-2b
      playing a more significant role in development. During gastrulation, igf-2a and
      igf-2b are required for development of anterior neural structures and for
      regulation of genes critical to dorsal-ventral patterning. As development
      proceeds, igf-2a and igf-2b play anti-apoptotic roles. Gene expression analysis
      demonstrates that igf-2a and igf-2b play overlapping roles in angiogenesis and
      cardiac outflow tract development. Igf-2b is specifically required for cardiac
      valve development and cardiac looping. Injection of a dominant negative IGF-1
      receptor led to similar defects in angiogenesis and cardiac valve development,
      indicating IGF-2 signals through this receptor to regulate cardiovascular
      development. This is the first study describing two functional igf-2 genes in
      zebrafish. This work demonstrates that igf-2a and igf-2b are critical to neural
      and cardiovascular development in zebrafish embryos. The finding that igf-2a and
      igf-2b do not act exclusively in a redundant manner may explain why both genes
      have been stably maintained in the genome.

PMID- 19757380
TI  - Gonadal defects in Cited2-mutant mice indicate a role for SF1 in both testis and
      ovary differentiation.
AB  - Sex determination is regulated by a molecular antagonism between testis- and
      ovary-determining pathways in the supporting cell lineage of the gonadal
      primordia. Genes important for maintaining this lineage play critical roles in
      early gonadal development, but their influence on testis and ovary
      differentiation is unclear due to the severity of loss-of-function phenotypes.
      The transcription factor SF1 (Nr5a1/Ad4BP) is one such factor, required for
      establishing the supporting cell lineage, and for propagating the male pathway.
      In the gonad, Sf1 expression is enhanced by the transcriptional co-factor Cited2.
      We have used the reduced levels of Sf1 expression in Cited2(-/-) mice as a
      hypomorphic model to gain insight into the sex-specific roles of SF1 function in
      gonadal development. In XY mutant mice, we found that testis development was
      delayed in Cited2(-/-) gonads, and that testis structure was permanently
      disrupted. In XX Cited2(-/-) gonads, ectopic cell migration was observed which
      correlated with a transient upregulation of Fgf9, and a delay in Wnt4 then Foxl2
      expression. These data suggest a novel role for SF1 in promoting ovarian
      development in addition to its roles in testis differentiation.

PMID- 19757381
TI  - Expression of protocadherin-19 in the nervous system of the embryonic zebrafish.
AB  - We have analyzed the expression pattern of protocadherin-19, a member of the
      delta2-protocadherins, in the nervous system of developing zebrafish using in
      situ hybridization methods. mRNA encoding protocadherin-19 (Pcdh19) began to be
      expressed at about 12 hours post fertilization (hpf) showing a segmental
      expression pattern in the anterior 1/3 of the neural keel, with strong expression
      in the presumptive forebrain, cerebellum/rhombomere 1 and rhombomere 4. Pcdh19
      expression in the posterior neural keel was continuous and confined to the
      midline region. By 24 hpf, Pcdh19 was expressed widely in the brain and spinal
      cord, with higher expression levels in the ventral telencephalon, dorsal and
      central thalamus, optic tectum, central tegmentum, cerebellum and dorsolateral
      regions of the hindbrain. As development proceeded, Pcdh19 expression domains
      became restricted to the dorsal and/or lateral regions of the central nervous
      system, and Pcdh19 expression was not detected in the spinal cord of two- and
      three-day old embryos. Pcdh19 was also expressed by the eye primordium,
      developing retina, lens and otic vesicle. Similar to its expression in the brain,
      Pcdh19 expression in the eye and ear was also spatially and temporally regulated.

PMID- 19757382
TI  - Zebrafish grainyhead-like1 is a common marker of different non-keratinocyte
      epidermal cell lineages, which segregate from each other in a Foxi3-dependent
      manner.
AB  - Grainyhead/CP2 transcription factor family members are widely conserved among the
      animal kingdom and have been implicated in different developmental processes.
      Thus far, nothing has been known about their roles in zebrafish. Here we identify
      seven zebrafish grainyhead-like (grhl) / cp2 genes, with focus on grhl1, which is
      expressed in the periderm and in epidermal ionocyte progenitors, but
      downregulated when ionocytes differentiate. In addition, expression was detected
      in other "non-keratinocyte" cell types of the epidermis, such as pvalb8
      expressing cells, which according to our lineage tracing experiments are derived
      from the same pool of progenitor cells like keratinocytes and ionocytes.
      Antisense morpholino oligonucleotide-based loss-of-function analysis revealed
      that grhl1 is dispensable for the development and function of all investigated
      epidermal cell types, but required as a negative regulator of its own
      transcription during ionocyte differentiation. Knockdown of the transcription
      factor Foxi3a, which is expressed in a subset of the grhl1 population, caused a
      loss of ionocytes and a corresponding increase in the number of pvalb8-expressing
      cells, while leaving the number of grhl1-positive cells unaltered. We propose
      that grhl1 is a novel common marker of all or most "non-keratinocyte" epidermal
      progenitors, and that the sub-functionalisation of these cells is regulated by
      differential positive and negative effects of Foxi3 factors.

PMID- 19757383
TI  - Regulatory elements of Xenopus col2a1 drive cartilaginous gene expression in
      transgenic frogs.
AB  - This study characterizes regulatory elements of collagen 2 alpha 1 (col2a1) in
      Xenopus that enable transgene expression in cartilage-forming chondrocytes. The
      reporters described in this study drive strong cartilage-specific gene
      expression, which will be a valuable tool for further investigations of Xenopus
      skeletal development. While endogenous col2a1 mRNA is expressed in many embryonic
      tissues, its expression becomes restricted to tadpole and adult chondrocytes.
      This chondrocyte-specific expression is recapitulated by col2a1 reporter
      constructs, which were tested through I-SceI meganuclease-mediated transgenesis.
      These constructs contain a portion of the Xenopus tropicalis col2a1 intron, which
      aligns to a cartilage-specific intronic enhancer that has been well characterized
      in mammals. Two overlapping regions of the first intron that are 1.5-Kb and 665
      bp long, both of which contain this enhancer sequence, drove EGFP expression in
      both larval and adult chondrocytes when connected to an upstream promoter.
      However, neither a truncated 155-bp region that also contains the enhancer, nor a
      separate 347-bp intronic region that lacks it, was able to drive cartilaginous
      transgene expression. The two cartilage-specific transgenes are heritable in F1
      progeny, which exhibit none of the background expression observed in the injected
      founders. This study is the first to use the I-SceI technique to characterize an
      enhancer element in Xenopus, and the first to generate chondrocyte-specific gene
      expression in a non-mammalian vertebrate. The creation of novel cartilage
      specific gene expression provides a new tool for further studies of anuran
      skeletal development.

PMID- 19757384
TI  - In vitro germ cell differentiation during sex differentiation in a teleost fish.
AB  - To clarify the sexually dimorphic mechanisms of gonadal sex differentiation, we
      established an in vitro culture system for gonadal sex differentiation using the
      teleost fish Oreochromis niloticus. In vivo, the entry of germ cells into meiosis
      occurs around 35 days after hatching (dah) in XX gonads, whereas in XY gonads,
      meiotic cells became differentiated around 85 dah. In our in vitro culture system
      using gonads from young fry at 23 dah, the meiotic cells in the XX gonads
      appeared after 21 days of culture. In contrast, in the XY gonads, no meiotic
      cells were detected after 21 days. These results indicate that germ cell
      differentiation in this culture system progresses in a manner similar to that in
      vivo. To identify the gene products that are involved in the entry of germ cells
      into meiosis or in the arrest of germ cells at the gonial stage of gonadal sex
      differentiation, we performed subtractive hybridization screening with this in
      vitro culture system. From the screening process, we identified the female
      related gene, FR-3, which is a homolog of zebrafish nanos-related gene (nos). The
      nos gene was expressed after gonadal formation around 35 dah in XX gonads, but
      not in XY gonads. In situ hybridization indicated that nos is expressed in
      oogenic meiotic cells, but not in spermatogenic meiotic cells. Further
      examination revealed that nos was expressed in oogenic meiotic cells after
      gonadal formation, specifically in teleost fish. Together, nos may be also
      involved in oogenic meiosis, with the exception of primordial germ cell
      migration.

PMID- 19757385
TI  - TGFbeta3 is expressed in differentiating muscle of the embryonic mouse tongue.
AB  - The purpose of the present study was to elucidate the involvement of transforming
      growth factor betas (TGFbetas) in the differentiation of tongue striated muscles
      by analyzing the expression of TGFbetas, their receptors and factors of TGFbeta
      signal transduction in the mouse tongue between embryonic days 11 (E11) and E15.
      The expression levels of TGFbeta3 mRNA and protein were much higher than those of
      TGFbeta1 and TGFbeta2, and the immunolocalization of TGFbeta3 was more consistent
      with the differentiating muscle cells in comparison with those of TGFbeta1 and 2
      between E12 and E15. TGFbetaRI and II were localized to the differentiating
      muscle cells between E11 and E15. Phosphorylated-smad2/3 was localized to the
      nucleus of muscle cells which just began to differentiate. These results suggest
      that the signal of TGFbeta3, but not that of beta1 or beta2, may be involved in
      the early stages (particularly the beginning) of differentiation of mouse tongue
      muscle cells through TGFbetaRI, TGFbetaRII, and smad2/3.

PMID- 19757386
TI  - Immunoregulatory molecules in human placentas: potential for diverse roles in
      pregnancy.
AB  - Molecules with immunological functions abound in hemochorial mammalian placentas
      where maternal blood and tissues are in direct contact with fetal placental
      cells. For the most part, investigators have focused on the possibility that
      these molecules are primarily in place for the purpose of preventing maternal
      immune mechanisms from attacking the genetically different fetal cells. Yet
      information collected in recent years indicates that these immunological
      mediators may serve other, non-immunological functions in placentas. In this
      article we discuss two families of these molecules investigated in our and other
      laboratories, namely the tumor necrosis factor superfamily (TNFSF) and the human
      leukocyte antigen (HLA) family, and present accumulating evidence for dichotomy
      of function during gestation.

PMID- 19757387
TI  - Early expression of axon guidance molecules in the embryonic chick mesencephalon
      and pretectum.
AB  - Early axon tracts in the developing vertebrate brain are established along
      precise paths. Yet, little is known about axon guidance processes at early stages
      of rostral brain development. Using whole mount in situ hybridisation in
      combination with immunohistochemistry, we have analysed the expression patterns
      of Slits, Netrins, Semaphorins and the respective receptors during the formation
      of the early axon scaffold, particularly focusing on the pretectal-mesencephalic
      boundary. Many of these guidance molecules are expressed in close correlation
      with the growing tracts, and the nuclei of the corresponding neurons often
      express the respective receptors. The expression patterns of Slits and Netrins
      implicate them with the positioning of the longitudinal tracts along the
      dorsoventral axis, while Semaphorins could provide guidance at specific choice
      points. Our study provides a catalogue of gene expression for future studies on
      axon guidance mechanisms in the early brain.

PMID- 19757388
TI  - A stem cell-derived gene (Sddr) negatively regulates differentiation of embryonic
      stem cells.
AB  - Embryonic stem (ES) cells, derived from the inner cell mass of blastocysts, are
      pluripotent and continue to self-renew. To better understand the molecular
      mechanisms underlying self-renewal, we have been searching for a gene(s) which is
      specifically expressed in self-renewing ES cells. Here we report the isolation
      and characterization of a novel gene, Sddr (stem cell-derived differentiation
      regulator). Sddr was highly expressed in undifferentiated ES cells, and its
      expression was downregulated upon differentiation. In addition to ES cells, Sddr
      expression was observed strongly in ovary, and weakly in lung. Immunostaining and
      cellular fractionation analyses suggested that Sddr is a cytoplasmic protein
      associated with the cytoskeleton. Sddr-null ES cells showed no remarkable
      abnormalities in their undifferentiated state. In contrast, in differentiating
      Sddr-null cells, induction of several differentiation-associated markers was
      enhanced, and downregulation of self-renewal marker genes was accelerated, as
      compared with wild-type cells. These results suggest that although it is
      dispensable for ES cell self-renewal, Sddr is a negative regulator of ES cell
      differentiation.

PMID- 19757389
TI  - Retinoic acid is both necessary for and inhibits myogenic commitment and
      differentiation in the chick limb.
AB  - Retinoic acid (RA) plays an essential role in the development of many embryonic
      tissues, including the developing tetrapod limb bud. At early stages of limb
      development, RA levels are highest proximally and regulate the migration of
      myoblasts into the limb. As the premyogenic progenitor cells migrate into the
      limb and accumulate in premuscle masses, they express Pax3 and Meox2. Myogenic
      differentiation is initiated by expression of Myf5 and MyoD, and both Pax3 and
      Meox2 are required for normal Myf5 expression. We show by loss of function using
      the inhibitor citral, that RA signalling within the limb bud is required to
      maintain Pax3 and Meox2 in the progenitor and Myf5 and MyoD in the
      differentiating myoblasts. Treatment with excess RA showed a differential effect:
      Meox2 and Pax3 showed localised down-regulation of expression in the limb. In
      contrast, there was a dramatic down-regulation of expression of MyoD, Myf5 and
      Meox1. The down-regulation of myogenic gene expression in response to inhibition
      of RA signalling, and differential response to application of excess RA, in the
      absence of changes to cell proliferation and apoptosis, indicate that myogenic
      specification and differentiation in the developing limb possess a complex
      sensitivity to RA concentrations.

PMID- 19757390
TI  - Local regulation of implantation at the human fetal-maternal interface.
AB  - Embryo implantation and formation of a functional placenta are complex processes
      that require a plethora of regulatory molecules. In recent years, many of these
      mediators have been identified, often from studies in experimental animals.
      Furthermore, their expression patterns at the embryo-maternal interface in women
      have been characterized and provide clues to their potential actions. What has
      been missing in most cases is any experimental demonstration of their function.
      Proteases, cytokines and chemokines are among the molecules identified at the
      embryo-maternal interface. Functional studies of the protease, proprotein
      convertase (PC)6, the gp130 cytokines, leukemia inhibitory factor (LIF) and
      interleukin (IL)11 and the chemokines, CX3CL1 and CCL14 demonstrate potential
      actions within the uterine cavity. These actions include: enhancing blastocyst
      development, modifying adhesive properties of the blastocyst and the uterine
      epithelial surface, and providing chemotactic guidance to the blastocyst. As
      implantation proceeds, PC6 and IL-11 also act to drive decidualization. The
      products (proteases, chemokines and cytokines) produced by these decidual cells
      provide a unique environment. This is important for both directing and
      restraining trophoblast invasion and for leukocyte trafficking into the decidua
      until the placenta is fully established.

PMID- 19757391
TI  - The influence of the intrauterine environment on human placental development.
AB  - Development of the human placenta is modulated heavily by the intrauterine
      environment. During the first trimester, development takes place in a low oxygen
      environment supported by histiotrophic nutrition from the endometrial glands.
      Consequently, the rate of growth of the chorionic sac is almost invariable across
      this period, and is remarkably uniform between individuals. Towards the end of
      the first trimester the intrauterine environment undergoes radical transformation
      in association with onset of the maternal arterial circulation and the switch to
      haemotrophic nutrition. The accompanying rise in intraplacental oxygen
      concentration poses a major challenge to placental tissues, and extensive villous
      remodelling takes place at this time. Later in pregnancy a wide variety of
      stressors are capable of affecting placental growth, but in the human, the most
      common are nutrient deprivation and vascular compromise. The latter is usually
      secondary to deficient trophoblast invasion and can induce placental oxidative
      stress. Closely linked to oxidative stress is endoplasmic reticulum stress, and
      we recently provided the first evidence that the latter plays a major role in the
      pathophysiology of intrauterine growth restriction. The endoplasmic reticulum is
      a key regulator of protein synthesis, exerting its effects through the unfolded
      protein response. Consequently, we observed multiple blocks to translation
      initiation and elongation in growth restricted placentas. Nutrient deprivation
      also modulates protein synthesis through the mTOR pathway, and we demonstrated
      interactions between this pathway and endoplasmic reticulum stress. Protein
      synthesis inhibition therefore appears to be a common mechanism for regulating
      placental development under different adverse conditions.

PMID- 19757392
TI  - Trophoblast phagocytic program: roles in different placental systems.
AB  - Although not belonging to the class of professional phagocytes, in many species
      trophoblast cells exhibit intense phagocytic activity. The complete range of
      physiological functions of trophoblast phagocytosis has not yet been fully
      characterized. Close association between the trophoblast and nutrition was
      determined many years ago. Hubrecht (1889) when proposing for the first time the
      name trophoblast to the external layer of the blastocyst, directly established
      the nutritive significance of this embryonic layer. Indeed, histotrophic
      phagocytosis, i.e. the internalization of maternal cells and secreted materials,
      is considered an important function of the trophoblast before the completion of
      the placenta. Recently, however, unexpected characteristics of the trophoblast
      have significantly enhanced our understanding of this process. Roles in
      acquisition of space for embryo development, in tissue remodeling during
      implantation and placentation and in defense mechanisms are highlighting how this
      cellular activity may be relevant for the maternal-fetal relationship beyond its
      nutritional function.

PMID- 19757393
TI  - The contribution of Roberto Montesano to the study of interactions between
      epithelial sheets and the surrounding extracellular matrix.
AB  - The interactions between epithelial cells and the surrounding extracellular
      matrix are a central issue in morphogenesis studies. Roberto Montesano and
      colleagues at the University Medical Center of Geneva, Switzerland, have
      extensively investigated the mechanisms underlying two morphogenetic processes:
      the formation of new capillary blood vessels from pre-existing ones
      (angiogenesis) and the generation of branching epithelial tubules
      (tubulogenesis), which are crucial events in the development of most parenchymal
      organs. Dr. Montesano has contributed to clarifying some cellular and molecular
      mechanisms of angiogenesis and tubulogenesis using an original three-dimensional
      cell culture system which replicates key events of angiogenesis and
      tubulogenesis, thereby facilitating molecular analysis. A major advance of this
      technique over conventional monolayer cultures is that cells can be embedded
      within a lattice of reconstituted collagen fibrils which mimics the three
      dimensional organization of connective tissue matrices.The results of these
      studies support the notion that cell interactions with the surrounding
      extracellular matrix are crucial determinants of cell responses to growth factors
      and that epithelial tissues morphogenesis is governed by the interplay of two
      different classes of signaling molecules, i.e. paracrine-acting growth factors
      and insoluble extracellular matrix components.

PMID- 19757394
TI  - Identification of a target for CudA, the transcription factor which directs
      formation of the Dictyostelium tip organiser.
AB  - The tip of the Dictyostelium slug functions much like an embryonic organiser;
      when grafted onto the flank of a recipient slug, it recruits a mass of prespore
      cells and leads them away as part of a secondary slug. CudA is a nuclear protein
      which is expressed in prespore cells where it acts as a specific transcription
      factor. CudA is also expressed in an anteriorly located group of cells, the tip
      organiser, that is believed to constitute the functional tip. We identify an
      expansin-like gene, expl7, that is expressed within the tip-organiser region and
      which is not expressed in a cudA null strain. The expl7 promoter contains a
      region that binds to CudA in vitro and this region is necessary for expression in
      the tip-organiser. These results provide an end-point for a previously defined
      signal transduction pathway in which regionalized expression of the ACA adenylyl
      cyclase within the tip-organiser leads to localised cAMP-induced activation of
      STATa and consequent binding of STATa to the cudA promoter. STATa then induces
      expression of cudA and cudA directs the transcription of target genes such as
      expl7.

PMID- 19757395
TI  - Differential expression of the Brunol/CELF family genes during Xenopus laevis
      early development.
AB  - The BRUNOL/CELF family of RNA-binding proteins plays important roles in post
      transcriptional regulation and has been implicated in several developmental
      processes. In this study, we describe the cloning and expression patterns of five
      Brunol genes in Xenopus laevis. Among them, only Brunol2 is maternally expressed
      and the zygotic expression of the other four Brunol genes starts at different
      developmental stages. During Xenopus development, Brunol1, 4-5 are exclusively
      expressed in the nervous system including domains in the brain, spinal cord,
      optic and otic vesicles. Brunol2 and 3 are expressed in both the somatic mesoderm
      and the nervous system. Brunol2 is also extensively expressed in the lens. In
      transfected Hela cells, BRUNOL1, 2 and 3 proteins are localized in both the
      cytoplasm and the nucleus, while BRUNOL4 and 5 are only present in the cytoplasm,
      indicating their different functions.

PMID- 19757396
TI  - Jose-Antonio Campos-Ortega (1940-2004) and his scientific work - a personal
      perspective.
AB  - Jose Antonio Campos-Ortega (1940-2004), a Spanish scientist who became a leading
      figure in the developmental genetics of the nervous system, spent most of his
      scientific life in Germany. Nevertheless, he remained deeply rooted in his native
      country. His thinking, his ambition and his work were driven by scientific,
      philosophical and historical questions. He started as a neuroanatomist, working
      first in Valencia, then in Gottingen, Tubingen and Freiburg. He used primates,
      reptiles, then the house fly and finally Drosophila to address the question How
      is the brain or the eye structured in order to function?. While in Freiburg, the
      problem shifted to How does the nervous system come into being, into form? Campos
      Ortega tried to understand early neurogenesis in Drosophila through formal
      genetics, by identifying relevant genes and studying their genetic interactions.
      Since he was convinced that not only a single experimental approach could solve a
      problem as complex as the development of the nervous system, he also included the
      molecular biological approach when he moved to Cologne, while maintaining a
      strong focus on anatomy, embryology and genetics. There, he also started to work
      on the neurogenesis of the zebrafish, using similar concepts and approaches.
      Throughout his scientific career, he thought, wrote and taught about the
      evolution of methods and ideas in his field of research. At Campos-Ortegas early
      death, an unfinished book manuscript was left, entitled Developmental Genetics.
      The Path to the Biological Synthesis. Some parts of his introductory overview are
      included here.

PMID- 19757397
TI  - Epiblast-derived stem cells in embryonic and adult tissues.
AB  - Pluripotent cells can be isolated from the mammalian inner cell mass (ICM) of the
      embryo at the blastocyst stage, and maintained in culture as undifferentiated,
      embryonic stem cells (ES). These cells are an important model of mammalian
      development in vitro and are the focus of a great deal of research for their use
      in Cell Therapy. In vivo, shortly after the blastocyst stage, the ICM segregates
      into two layers: the hypoblast which will give rise to the yolk sac, and the
      epiblast. Epiblast stem cells, like ES cells, are pluripotent. The epiblast will
      differentiate very early into germ cell progenitors, the primordial germ cells
      (PGC). PGCs can give rise to embryonal carcinoma cells, the pluripotent stem
      cells of testicular tumors. During normal embryo development, PGCs migrate into
      the aorta-gonad-mesonephros region (AGM). Interestingly, this region also harbors
      the first wave of embryonic hematopoiesis. Subsequent waves of hematopoiesis
      involve AGM-hematopoietic stem cell (HSC) colonization of the fetal liver,
      thymus, spleen and ultimately, for adult hematopoiesis, the bone marrow (BM). The
      BM is also source of mesenchymal stem cells (MSCs). It is accepted that the AGM
      region cells give rise to the mesothelial cells which are the embryonic
      precursors of the HSC and MSC of the BM. Recent identification of a subpopulation
      of cells with markers typical of PGCs in the adult BM, which are capable of
      differentiating into HSCs, suggests that HSCs originate from a common precursor
      of PGCs and HSCs derived from the epiblast. Several groups have described the
      presence of stem cells with the same markers in epidermis, bronchial epithelium,
      pancreas, retina, hair follicle, heart and dental pulp among, other organs. This
      presence supports the hypothesis that during early development, epiblast/germ
      line-derived cells are deposited in various organs which persist into adulthood.
      The question remains whether these pluripotent stem cells are only developmental
      remnants or if they continuously contribute to the renewal of tissues, and thus
      can be reactivated for tissue regeneration without the need for stem cell
      transplantation for human cell therapies.

PMID- 19757398
TI  - A role for Dimethylarginine Dimethylaminohydrolase 1 (DDAH1) in mammalian
      development.
AB  - Nitric oxide has been linked to a number of embryonic processes, yet the role of
      nitric oxide signalling in development remains largely unknown. Dimethylarginine
      Dimethylaminohydrolase 1 and 2 (DDAH1/2) catalyse the breakdown of asymmetric
      dimethylarginine, an endogenous inhibitor of nitric oxide production, and may
      also have nitric oxide-independent functions. We have generated transgenic mice
      targeting the DDAH1 and DDAH2 loci. Here we report that homozygous DDAH1 null
      embryos are generated at low frequency, and do not progress through embryonic
      development. During normal development DDAH1 RNA is expressed in the left
      ventricle, cardiac outflow tract and developing vasculature. In contrast, DDAH2
      homozygous null mice are viable and fertile, with a normal lifespan. DDAH2
      expression is seen in the developing left ventricle and cardiac outflow tract,
      and additionally in the peripheral nervous system. Both DDAH1 and 2 are expressed
      in the developing limb buds in patterns overlapping areas with high nitric oxide
      synthase activity. These expression patterns implicate DDAH1 and DDAH2 in
      embryonic development, possibly through specific effects on nitric oxide
      pathways.

PMID- 19757399
TI  - A personal account of the development of modern biological research in Portugal.
AB  - Portugal celebrated in 2006 its first 20 years of the formal introduction of the
      practice of external evaluation of research proposals in the national funding
      system. Accounts of changes in numbers of publications, citations, numbers of
      research projects funded and budget figures can be found in Government Reports
      (www.oces.mctes.pt.). An offshoot of the decisive and firm implementation of that
      practice in what was to become the Health Sciences was that the area became an
      attractor for young researchers in the basic biological sciences, namely,
      molecular, cellular and developmental biology. Reciprocally, the entry of basic
      biological scientists into medically oriented groups totally changed the
      landscape, the soil, the seeding, the cross-fertilization and the flowering of
      biomedical research in the country. This paper is a personal account of the
      experience of a scientist who was asked by the then President of the National
      Research Council, Jose Mariano Gago to co-ordinate the introduction of external
      evaluation of research projects and research institutes in the Health Sciences in
      Portugal between 1986 and 1997.

PMID- 19757401
TI  - Confidence of expert ultrasound operators in making a diagnosis of adnexal tumor:
      effect on diagnostic accuracy and interobserver agreement.
AB  - OBJECTIVE: To assess the degree of confidence with which expert ultrasound
      operators make a diagnosis of benign, borderline and invasive malignant ovarian
      tumors and its effect on diagnostic accuracy and interobserver agreement. METHOD:
      Digitally stored static two-dimensional B-mode images of representative cases of
      benign, borderline and invasive malignant ovarian tumors were independently
      assessed by three expert ultrasound operators who had not performed the original
      real-time ultrasound examination. The experts classified the tumors as benign,
      borderline or invasive malignant and they also indicated the degree of confidence
      with which they made the diagnosis (certain, probable and uncertain). The
      diagnostic accuracy and interobserver agreement, in differentiating benign,
      borderline and invasive malignant ovarian tumors, were calculated depending on
      the level of confidence with which the diagnosis was made. RESULTS: One hundred
      and sixty-six cases were included in the final data analysis. The diagnostic
      accuracy of all three experts decreased with decreasing level of confidence.
      Interobserver agreement between any two experts was very high when they were
      certain of the diagnosis (rates of agreement 98%, 99% and 100%), but it was
      significantly lower with a moderate level of confidence (rates of agreement 78%,
      71% and 76%) (P < 0.01 for any two experts). The agreement in both diagnosis and
      confidence was lowest in cases of borderline ovarian tumors compared to benign
      and primary invasive lesions. CONCLUSIONS: The accuracy of expert ultrasound
      operators using pattern recognition depends on the degree of certainty with which
      the diagnosis is made. Interobserver variability is also influenced by the
      operators' confidence in making the diagnosis. Our findings suggest that the
      level of confidence with which the diagnosis is made should be included in the
      ultrasound report.

PMID- 19757402
TI  - Prenatal diagnosis and pulmonary pathology in congenital high airway obstruction
      sequence.

PMID- 19757403
TI  - Hydroacridines: part 30. 1H and 13C NMR spectra of 9-substituted 1,2,3,4,5,6,7,8
      octahydroacridines and of their N-oxides.
AB  - The 1H and 13C NMR chemical shifts of 1,2,3,4,5,6,7,8-octahydroacridine, 12 of
      its 9-substituted derivatives, and of the corresponding N-oxides were determined,
      assigned, and discussed in terms of 9-substituent effects and effects of N
      oxidation. A good linear correlation was found between the 13C chemical shifts of
      the aromatic carbons in octahydroacridines and those of respective carbons in the
      corresponding N-oxides.

PMID- 19757404
TI  - TNF-alpha, a potent lipid metabolism regulator.
AB  - As a multifunctional cytokine, tumor necrosis factor alpha (TNF-alpha) exerts a
      series of biological actions in different cells, tissues, organs, and species and
      has been demonstrated to regulate and interfere with energy metabolism,
      especially lipid homeostasis. A large body of researches suggested that the
      effects of TNF-alpha on lipid metabolism mainly include five aspects: (1)
      suppresses free fatty acid (FFA) uptake and promotes lipogenesis; (2) induces
      lipolysis; (3) inhibits lipid-metabolism-related enzymes activity; (4) regulates
      cholesterol metabolism; (5) regulates other adipocyte-derived adipokines. The
      molecular mechanisms underlying these actions are complex and several signal
      transduction pathways might be involved. Regulation of metabolism-related gene
      expression at transcriptional and protein levels and impact on enzymes activity
      might be of importance. Identification and verification of these pathways might
      provide novel potential strategies and drug targets for dyslipidemia therapy.
      However, the inconsistent and even conflict conclusions on lipid profile drawn
      from human subjects after infliximab therapy poses the possibility that the
      effect of TNF-alpha on lipid metabolism might be more complicated than it
      appeared to be.

PMID- 19757405
TI  - The effect of antagonists on the conformational exchange of the retinoid X
      receptor alpha ligand-binding domain.
AB  - The effect of retinoid X receptor (RXR) antagonists on the conformational
      exchange of the RXR ligand-binding domain (LBD) remains poorly characterized. To
      address this question, we used nuclear magnetic resonance spectroscopy to compare
      the chemical shift perturbations induced by RXR antagonists and agonists on the
      RXRalpha LBD when partnered with itself as a homodimer and as the heterodimeric
      partner with the peroxisome proliferator-activated receptor gamma (PPARgamma)
      LBD. Chemical shift mapping on the crystal structure showed that agonist binding
      abolished a line-broadening effect caused by a conformational exchange on
      backbone amide signals for residues in helix H3 and other regions of either the
      homo- or hetero-dimer, whereas binding of antagonists with similar binding
      affinities failed to do so. A lineshape analysis of a glucocorticoid receptor
      interacting protein 1 NR box 2 coactivator peptide showed that the antagonists
      enhanced peptide binding to the RXRalpha LBD homodimer, but to a lesser extent
      than that enhanced by the agonists. This was further supported by a lineshape
      analysis of the RXR C-terminal residue, threonine 462 (T462) in the homodimer but
      not in the heterodimer. Contrary to the agonists, the antagonists failed to
      abolish a line-broadening effect caused by a conformational exchange on the T462
      signal corresponding to the RXRalpha LBD-antagonist-peptide ternary complex.
      These results suggest that the antagonists lack the ability of the agonists to
      shift the equilibrium of multiple RXRalpha LBD conformations in favor of a
      compact state, and that a PPARgamma LBD-agonist complex can prevent the
      antagonist from enhancing the RXRalpha LBD-coactivator binding interaction.

PMID- 19757406
TI  - Competitive binding exchange between alkali metal ions (K+, Rb+, and Cs+) and Na+
      ions bound to the dimeric quadruplex [d(G4T4G4)]2: a 23Na and 1H NMR study.
AB  - A comparative study of the competitive cation exchange between the alkali metal
      ions K+, Rb+, and Cs+ and the Na+ ions bound to the dimeric quadruplex
      [d(G4T4G4)]2 was performed in aqueous solution by a combined use of the 23Na and
      1H NMR spectroscopy. The titration data confirm the different binding affinities
      of these ions for the G-quadruplex and, in particular, major differences in the
      behavior of Cs+ as compared to the other ions were found. Accordingly, Cs+
      competes with Na+ only for the binding sites at the quadruplex surface (primarily
      phosphate groups), while K+ and Rb+ are also able to replace sodium ions located
      inside the quadruplex. Furthermore, the 1H NMR results relative to the CsCl
      titration evidence a close approach of Cs+ ions to the phosphate groups in the
      narrow groove of [d(G4T4G4)]2. Based on a three-site exchange model, the 23Na NMR
      relaxation data lead to an estimate of the relative binding affinity of Cs+
      versus Na+ for the quadruplex surface of 0.5 at 298 K. Comparing this value to
      those reported in the literature for the surface of the G-quadruplex formed by 5'
      guanosinemonophosphate and for the surface of double-helical DNA suggests that
      topology factors may have an important influence on the cation affinity for the
      phosphate groups on DNA.

PMID- 19757407
TI  - Important roles of the hyphenated HPLC-DAD-MS-SPE-NMR technique in metabonomics.
AB  - Metabolite identification is a key step for metabonomics study. A fully automated
      hyphenation of HPLC-diode-array detector (DAD) mass spectrometry (MS) solid phase
      extraction (SPE)-NMR spectroscopy (HPLC-DAD-MS-SPE-NMR) is one of the most
      efficient methods to determine the structure of a given unknown metabolite in a
      complex mixture (metabonome) and hence represents one of the most important
      analytical techniques for the further development of metabonomics. In this
      review, some recent applications of this technique in identifying novel and trace
      metabolites in plant extracts and drug metabolism have been discussed.
      Modification of this hyphenated technique, enabling multiple trappings of strong
      polar metabolites for biofluids, needs further development.

PMID- 19757408
TI  - Implication of agathic acid from Utah juniper bark as an abortifacient compound
      in cattle.
AB  - Freshly ground Utah juniper [Juniperus osteosperma (Torr.) Little] bark was given
      via gavage at a dosage of 2.3 kg per cow twice daily to three pregnant cows
      starting on day 255 of gestation. All three cows aborted the calves after 4, 5
      and 6 days of treatment. A fourth cow was dosed with Utah juniper needles and
      this cow calved early on day 268 of gestation with complications consistent with
      pine needle abortion. Chemical analysis of Juniperus osteosperma bark identified
      the major diterpene acid as the labdane acid known as agathic acid. Agathic acid
      was measured in the bark at a concentration of 1.5% (dry weight basis). Analysis
      of sera samples obtained from treated cows found detectable quantities of agathic
      acid, dihydroagathic acid and tetrahydroagathic acid, which are known serum
      metabolites of the abortifacient compound isocupressic acid. Based on the high
      incidence of induced abortion and detection of known metabolites in affected
      animals, the labdane acid known as agathic acid is considered to be an
      abortifacient compound in late-term pregnant cattle.

PMID- 19757409
TI  - Cadmium chloride exposure modifies amino acid daily pattern in the mediobasal
      hypothalamus in adult male rat.
AB  - The present study was conducted to investigate the possible effects of cadmium
      exposure on the daily pattern of aspartate, glutamate, glutamine, gamma
      aminobutyric acid (GABA) and taurine levels in the mediobasal hypothalamus of
      adult male rats. For this purpose, animals were treated with cadmium at two
      different exposure doses (25 and 50 mg l(-1) of cadmium chloride, CdCl(2)) in the
      drinking water for 30 days. Control age-matched rats received CdCl(2)-free water.
      After the treatment, rats were killed at six different time intervals throughout
      a 24 h cycle. CdCl(2) exposure modified the amino acid daily pattern, as it
      decreased aspartate, glutamate, GABA and taurine levels at 12:00 h with both
      exposure doses employed. In addition, the treatment with 25 mg l(-1) of CdCl(2)
      induced the appearance of minimal values at 16:00 h and maximal values between
      04:00 and 08:00 h for glutamate, and a peak of glutamine content at 20:00 h. The
      heavy metal also decreased GABA medium levels around the clock in the mediobasal
      hypothalamus. However, CdCl(2) did not alter the metabolic correlation between
      glutamate, aspartate, glutamine and GABA observed in control animals. These
      results suggest that CdCl(2) induced several alterations in aspartate, glutamate,
      glutamine, GABA and taurine daily pattern in the mediobasal hypothalamus and
      those changes may be related to alterations in hypothalamic function.

PMID- 19757410
TI  - Metabolic fate of ultratrace levels of GeCl(4) in the rat and in vitro studies on
      its basal cytotoxicity and carcinogenic potential in Balb/3T3 and HaCaT cell
      linesdagger.
AB  - The use of germanium (Ge) and the possibility of exposure to trace and ultratrace
      amounts of this element is increasing. Germanium is widely used in the industrial
      field as a semiconductor and also as a dietary supplement, an elixir to 'promote
      health and cure disease' (e.g. cancer and AIDS). More recently, germanium
      nanoparticles, ranging in size from 60 to 80 nm, have been developed as a
      potential spleen imaging agent. Like other metal-based nanoparticles used in
      nanomedicine, Ge nanoparticles may release trace and ultratrace amounts of Ge
      ions when injected. The metabolic fate and toxicity of these ions still needs to
      be evaluated. In this study the metabolic fate of a cationic tetravalent Ge
      species was studied in vivo by injecting rats i.p. with ultratrace amounts of Ge
      (80 ng kg(-1)) as [(68)Ge]GeCl(4). The cytotoxicity and carcinogenic potential
      was assessed in vitro using immortalised human skin keratinocytes and mouse
      fibroblasts (HaCaT and Balb/c 3T3 cell lines, respectively). At 24 h post
      exposure Ge was poorly retained in rat tissues (kidney, liver, intestine, femur,
      spleen and the heart were the organs with the highest Ge concentration). In the
      blood, Ge was rapidly cleared, being almost equally distributed between plasma
      and red blood cells. The excretion was mainly via the urine. The hepatic and
      renal intracellular distribution showed the highest recovery of Ge in the cytosol
      and the nuclear fractions. Chromatographic separation and ultrafiltration
      experiments on kidney and liver cytosols showed that the bulk of Ge was
      associated with low molecular weight components, representing a 'mobile pool' of
      the element in the body. However, a significant part of the element was able to
      interact with biological macromolecules which could be responsible for the
      presence of Ge in the liver and kidney after 7 days. The in vitro experiments
      confirmed the low degree of cytotoxicity of GeCl(4) both in HaCaT and Balb/3T3.
      The latter model was more sensitive to the toxic effects induced by Ge as shown
      by a colony forming efficiency (CFE) greater than 70% at 700 microm of exposure.
      At the highest exposure concentration tested (700 microm) GeCl(4) failed to
      induce morphological neoplastic transformation of the cells, suggesting for the
      first time that a cationic form of Ge ions has no carcinogenic potential. This
      supports the results of the only study reported in mice, treated orally long-term
      to an anionic species of Ge such as sodium germanate (Kanisawa and Schroeder,
      1967).

PMID- 19757411
TI  - Identification of N-glycosylation in prolyl endoprotease from Aspergillus niger
      and evaluation of the enzyme for its possible application in proteomics.
AB  - An acidic prolyl endoprotease from Aspergillus niger was isolated from the
      commercial product Brewers Clarex to evaluate its possible application in
      proteomics. The chromatographic purification yielded a single protein band in
      sodium dodecyl sulfate polyacrylamide gel electrophoresis providing an apparent
      molecular mass of 63 kDa and a broad peak (m/z 58,061) in linear matrix-assisted
      laser desorption/ionization (MALDI) time-of-flight (TOF) mass spectrometry (MS)
      indicating the glycoprotein nature of the enzyme. Indeed, a colorimetric
      assessment with phenol and sulfuric acid showed the presence of neutral sugars
      (9% of weight). The subsequent treatment with N-glycosidase F released a variety
      of high-mannose type N-glycans, which were successfully detected using MALDI-TOF
      MS. MALDI-TOF/TOF tandem MS analysis of glycopeptides from a tryptic digest of
      prolyl endoprotease unraveled the identity of the N-glycosylation site in the
      primary structure. The data obtained also show that the enzyme is present in its
      processed form, i.e. without putative signal and propeptide parts.
      Spectrophotometric measurements demonstrated optimal activity at pH 4.0-4.5 and
      also high thermostability for the cleavage at the C-terminal part of proline
      residues. In-solution digestion of standard proteins (12-200 kDa) allowed to
      evaluate the cleavage specificity. The enzyme acts upon proline and alanine
      residues, but there is an additional minor cleavage at some other residues like
      Gly, Leu, Arg, Ser and Tyr. The digestion of a honeybee peptide comprising six
      proline residues (apidaecin 1A) led to the detection of specific peptides
      terminated by proline as it was confirmed by MALDI postsource decay analysis.

PMID- 19757412
TI  - Data mining on electronic health record databases for signal detection in
      pharmacovigilance: which events to monitor?
AB  - PURPOSE: Data mining on electronic health records (EHRs) has emerged as a
      promising complementary method for post-marketing drug safety surveillance. The
      EU-ADR project, funded by the European Commission, is developing techniques that
      allow mining of EHRs for adverse drug events across different countries in
      Europe. Since mining on all possible events was considered to unduly increase the
      number of spurious signals, we wanted to create a ranked list of high-priority
      events. METHODS: Scientific literature, medical textbooks, and websites of
      regulatory agencies were reviewed to create a preliminary list of events that are
      deemed important in pharmacovigilance. Two teams of pharmacovigilance experts
      independently rated each event on five criteria: 'trigger for drug withdrawal',
      'trigger for black box warning', 'leading to emergency department visit or
      hospital admission', 'probability of event to be drug-related', and 'likelihood
      of death'. In case of disagreement, a consensus score was obtained. Ordinal
      scales between 0 and 3 were used for rating the criteria, and an overall score
      was computed to rank the events. RESULTS: An initial list comprising 23 adverse
      events was identified. After rating all the events and calculation of overall
      scores, a ranked list was established. The top-ranking events were: cutaneous
      bullous eruptions, acute renal failure, anaphylactic shock, acute myocardial
      infarction, and rhabdomyolysis. CONCLUSIONS: A ranked list of 23 adverse drug
      events judged as important in pharmacovigilance was created to permit focused
      data mining. The list will need to be updated periodically as knowledge on drug
      safety evolves and new issues in drug safety arise.

PMID- 19757413
TI  - Calcium supplementation, cardiovascular disease and mortality in older women.
AB  - PURPOSE: To investigate the long-term cumulative effect of calcium and vitamin D
      supplementation on cardiovascular outcomes and death in older women. METHODS: We
      undertook an observational cohort study using UK electronic primary care records
      in the Doctor's Independent Network (DIN-LINK) database; 9910 women aged 60-89
      who started calcium and vitamin D supplementation between 2000 and 2005, with no
      heart disease or stroke history and who survived disease free for 2 years after
      supplement initiation were studied. The main outcome was first occurrence of
      myocardial infarction (MI), stroke or death more than 2 years after initiation.
      RESULTS: In the period from 2 years after supplement initiation, women who had
      received >600 days supplementation in these first 2 years were no more at risk of
      MI, stroke or death (hazard ratio 0.82 (0.67-1.01)) compared to women who
      received < or = 90 days supplementation in the first 2 years. Outcomes in the
      first 2 years were analysed separately and showed similar baseline risks in our
      comparison groups. CONCLUSION: Two years after initiation, women who have
      consistently received supplementation with calcium and vitamin D do not
      experience more cardiovascular events or deaths than women who received minimal
      supplementation.

PMID- 19757415
TI  - Change in editorial policy from January 2010: Discontinuation of the Spectral
      Assignments and Reference Data and Notes categories, and introduction of the new
      category MRC Letters.

PMID- 19757414
TI  - Systematic reviews of adverse effects of drug interventions: a survey of their
      conduct and reporting quality.
AB  - PURPOSE: There is a need for high quality evidence on the adverse effects of
      medical interventions to inform policy, practice and research. Methods to
      systematically review adverse effects have not been fully developed. We aimed to
      assess the current methods and reporting used by such reviews. METHODS: Survey of
      general medical, drug safety and pharmacology journals published in 2006. Methods
      including: searching, inclusion criteria, quality assessment and meta-analysis
      were assessed. RESULTS: Forty three systematic reviews from 2704 abstracts in 16
      journals were included. The search strategy was not reported by 10 (23%) of
      reviews. The collection and reporting of the adverse effects from primary studies
      was described by 4/37 (12%) reviews and the quality of included studies was
      assessed by 15 (35%) of reviews. Meta-analysis on rare outcomes and handling of
      zero event data were inconsistent. A polarity in the standard of reporting
      between reviews was observed. The reporting standard we found was similar to
      another survey of systematic reviews. CONCLUSION: Reporting was poor with respect
      to searching and definition/collection of adverse effects and guidelines such as
      QUOROM and MOOSE could be employed by authors. Comprehensive and clear reporting
      should be enforced by journals. The low proportion of reviews assessing quality,
      and the inconsistencies observed when modelling rare event data reflect the need
      for empirical research to underpin methods in these areas.

PMID- 19757416
TI  - Confounder summary scores when comparing the effects of multiple drug exposures.
AB  - PURPOSE: Little information is available comparing methods to adjust for
      confounding when considering multiple drug exposures. We compared three analytic
      strategies to control for confounding based on measured variables: conventional
      multivariable, exposure propensity score (EPS), and disease risk score (DRS).
      METHODS: Each method was applied to a dataset (2000-2006) recently used to
      examine the comparative effectiveness of four drugs. The relative effectiveness
      of risedronate, nasal calcitonin, and raloxifene in preventing non-vertebral
      fracture, were each compared to alendronate. EPSs were derived both by using
      multinomial logistic regression (single model EPS) and by three separate logistic
      regression models (separate model EPS). DRSs were derived and event rates
      compared using Cox proportional hazard models. DRSs derived among the entire
      cohort (full cohort DRS) was compared to DRSs derived only among the referent
      alendronate (unexposed cohort DRS). RESULTS: Less than 8% deviation from the base
      estimate (conventional multivariable) was observed applying single model EPS,
      separate model EPS or full cohort DRS. Applying the unexposed cohort DRS when
      background risk for fracture differed between comparison drug exposure cohorts
      resulted in -7 to + 13% deviation from our base estimate. CONCLUSIONS: With
      sufficient numbers of exposed and outcomes, either conventional multivariable,
      EPS or full cohort DRS may be used to adjust for confounding to compare the
      effects of multiple drug exposures. However, our data also suggest that unexposed
      cohort DRS may be problematic when background risks differ between referent and
      exposed groups. Further empirical and simulation studies will help to clarify the
      generalizability of our findings.

PMID- 19757417
TI  - Factors associated with a continuous regular analgesic use - a population-based
      study of more than 45,000 Danish women and men 18-45 years of age.
AB  - PURPOSE: Widespread use of and serious adverse effects associated with use of
      analgesics accentuates the need to consider factors related to analgesic use. The
      objective of this study was to describe continuous regular analgesics use and
      examine factors associated with a continuous regular analgesic use. METHODS: The
      study was based on data from two surveys and included a random sample of women
      and men aged 18-45 years from the general Danish population. Information on
      analgesics use, self-rated health, demographic and lifestyle factors was
      collected using a self-administered questionnaire. A total of 28,000 women and 33
      000 men were invited to participate and 22,199 women (response-rate 81.4%) and
      23,080 men (response-rate 71.0%), respectively, were included in the study. Data
      were analyzed using multivariate logistic regression. RESULTS: We found that 27%
      of the women and 18% of the men reported a regular monthly use of at least seven
      analgesic tablets during the last year (continuous regular analgesics use).
      Besides poor self-rated health we found in both sexes that increasing age, poor
      self-rated fitness, and smoking were related to a continuous regular analgesics
      use. Nulliparity, low level of education, overweight/obesity, binge drinking, and
      abstinence were associated with a continuous regular analgesics use for women,
      while underweight and marital/cohabiting status were associated with a continuous
      regular analgesics use only for men. CONCLUSIONS: Regular monthly analgesic use
      during the last year was generally prevalent. Besides self-rated health, several
      socio-demographic and lifestyle factors were associated with a continuous regular
      analgesic use, although with some gender differences.

PMID- 19757418
TI  - Advances in protein turnover analysis at the global level and biological
      insights.
AB  - The concept of a dynamic state of body constituents, a precursor of the modern
      term of proteome dynamics, was conceived over a century ago. But, not until
      recently can we examine the dynamics of individual "constituents" for example,
      proteins at a truly global level. The path of advancement in our understanding of
      protein turnover at the global level is marked by the introduction of some key
      technological innovations. These methods include the isotopic tracer technique in
      the 1930s, the two-dimensional gel electrophoresis technique in the 1970s, the
      sector mass spectrometer that could analyze isotopomers of peptides in the early
      1990s, the 2D gel/MALDI-TOF proteomics technology in the late 1990s, the booming
      liquid chromatography/mass spectrometry proteomics technology in this decade, and
      the recently emerging protein-tagging approaches that offer single-cell
      resolution for protein turnover measurements. The long-standing inquiry raised in
      the 1950s about the existence of a dynamic state in different organisms at
      different physiological conditions can now be answered with an individual
      "constituent" resolution on a truly global scale. Now it appears that protein
      degradation is not necessarily an end to the protein function. Rather, it can be
      the start of a new function because protein degradation clears the way for the
      action of other proteins. Protein turnover participates in a multi-layer complex
      regulatory network and shares equal importance with gene transcription and
      protein translation. The advances in technologies for protein turnover analysis
      and the improved understanding of the biological role of protein turnover will
      likely help to solve some long-standing biomedical problems such as the
      tuberculosis disease that at the present day still affects one-third of the world
      population.

PMID- 19757419
TI  - Segmental cystic renal disease: sonographic and CT findings.

PMID- 19757421
TI  - HPV-positive/p16-positive/EBV-negative nasopharyngeal carcinoma in white North
      Americans.
AB  - BACKGROUND: Human papillomavirus (HPV) has been detected in keratinizing
      nasopharyngeal carcinomas (NPCs); however, the relationship between HPV and
      Epstein-Barr virus (EBV) among whites with nonkeratinizing NPCs remains unclear.
      The HPV, p16, and EBV status was examined in current University of Michigan
      patients with NPC. METHODS: From 2003 to 2007, 89 patients, 84 with oropharyngeal
      cancer (OPC) and 5 with NPC, were enrolled in an organ-sparing trial. Biopsy
      tissues from all 89 patients were evaluated for HPV and p16 expression. A
      separate HPV analysis of the 84 OPC patients is in progress. Among the patients
      with NPC, tumor tissue was also analyzed for EBV-encoded RNA (EBER). RESULTS:
      Five of 89 patients (5.6%) had NPC, all with nonkeratinizing histology. The 4
      white patients with NPC were HPV(+) (subtype-16, subtype-18 [2 patients], and
      subtype-59)/p16(+)/EBER(-). One Asian patient with NPC had an HPV(-)/p16(
      )/EBER(+) NPC tumor that developed distant metastases. CONCLUSION: We postulate
      that HPV may be the etiologic factor in some EBV-negative, nonkeratinizing NPCs
      among whites.

PMID- 19757423
TI  - Splenic necrosis as a rare complication of dengue fever.

PMID- 19757422
TI  - Comprehensive IMRT plus weekly cisplatin for advanced head and neck cancer: the
      University of Wisconsin experience.
AB  - BACKGROUND: We retrospectively examined the treatment efficacy and toxicity
      profile of intensity-modulated radiotherapy (IMRT) plus concurrent weekly
      cisplatin chemotherapy in patients with locoregionally advanced head and neck
      squamous cell carcinoma (HNSCC). METHODS: A total of 57 patients with stage III
      or IV HNSCC were treated with IMRT and concurrent weekly cisplatin (dosed at 30
      mg/m(2)) between November 2001 and May 2007. The median prescription dose to the
      gross tumor volume was 70 Gy (using 2.0-2.2 Gy daily fractions). RESULTS: In
      field tumor control at 2 years was 89.1%, locoregional control was 85.5%, and
      overall survival was 86.9%. The median radiation dose delivered was 70 Gy. The
      mean dose intensity of cisplatin administered was 25.7 mg/m(2)/week. CONCLUSION:
      Comprehensive head and neck IMRT to 70 Gy delivered with weekly cisplatin
      chemotherapy (30 mg/m(2)) is feasible and generally well tolerated.

PMID- 19757424
TI  - Sonographic diagnosis and monitoring of an intramural duodenal hematoma following
      upper endoscopic biopsy in a child.
AB  - Intramural duodenal hematoma is an uncommon complication of pediatric endoscopic
      biopsy that occurs mainly in children with bleeding disorders. We report the case
      of a 5-year-old girl who presented with signs of partial duodenal obstruction and
      acute pancreatitis due to duodenal hematoma following endoscopic biopsy. The
      lesion was diagnosed and monitored by sonography and resolved with conservative
      management.

PMID- 19757426
TI  - Serial compression B-scan and Doppler sonography for the screening of deep venous
      thrombosis in patients with spinal cord injuries.
AB  - PURPOSE: To evaluate the usefulness of serial compression B-scan and Doppler
      sonography (US) in screening for deep venous thrombosis (DVT) of the lower
      extremities in patients with spinal cord injuries. METHOD: Patients with
      paraplegia and tetraplegia due to spinal cord injuries were screened by a serial
      compression B-scan and Doppler US protocol for DVT of the bilateral lower
      extremities within the first 36 hours after admission, at day 7 and at day 21. In
      patients with DVT, a follow-up US examination was performed 3 weeks after
      diagnosis to assess thrombi distribution. RESULTS: Between January 2007 and March
      2008, a total of 115 patients (75 males, 40 females), aged 19 to 85 years, were
      included. The first US examination documented a DVT in 44 cases (38.3%). After an
      initial negative scan, sonography after 7 days and 21 days showed DVT in 6
      patients and 2 patients, respectively. Cumulative rate of DVT after the first 3
      weeks was 45.2% (n=52). Follow-up US after 3 weeks in patients with DVT
      documented a complete recanalization in 19 patients (36.5%), no change in 12
      patients (23.1%), and residual thrombi with partial recanalization in 21 patients
      (40.4%). CONCLUSION: Our study supports the use of serial compression B-scan and
      Doppler US as a screening tool for DVT of the lower extremities in patients with
      spinal cord injuries early after injury.

PMID- 19757428
TI  - The trivialization of diagnosis.
AB  - Although it is widely recognized that diagnosis plays a central role in clinical
      medicine, in recent years the primacy of diagnosis has come under attack from
      several sources. 1. "Billable terms" are replacing traditional medical diagnoses.
      The former are based on International Classification of Diseases lists, which
      include many non-diagnoses such as symptoms and signs. 2. Diagnosis often gets
      short shrift because of the perceived urgency of discharge. 3. The problem
      oriented record, in practice, has frequently led to a shift in emphasis from
      synthesis of findings to fragmentation of problems. 4. Presumptive diagnoses
      frequently metamorphose into established diagnoses in medical records, even if
      incorrect. 5. A number of authors have apparently disparaged the importance of
      diagnosis. Nonetheless, it is clear that diagnosis must continue to play a
      central role in clinical medicine. We propose several ways by which we can resist
      these forces and assure that diagnosis retains its appropriate position of
      primacy.

PMID- 19757430
TI  - Enantioselective Friedel-Crafts alkylation of 4,7-dihydroindoles with enones
      catalyzed by primary-secondary diamines.

PMID- 19757431
TI  - Ferromagnetic Ni(II) discs.
AB  - A family of planar disc-like hexa-, octa- and decametallic Ni(II) complexes
      exhibit dominant ferromagnetic exchange. The deca- and octametallic clusters
      [Ni(II) (10)(tmp)(2)(N(3))(8)(acac)(6)(MeOH)(6)] (1, H(3)tmp=1,1,1
      tris(hydroxymethyl)propane; acac=acetylacetonate) and [Ni(II)
      (8)(thme)(2)(O(2)CPh)(4)(Cl)(6)(MeCN)(6)(H(2)O)(2)] (2, H(3)thme=1,1,1
      tris(hydroxymethyl)ethane) represent rare examples of Ni(II)-based single
      molecule magnets, and [Ni(II) (10)] (1) possesses the largest barrier to
      magnetisation reversal of any Ni(II) single-molecule magnet to date.

PMID- 19757432
TI  - Response adaptive designs with a variance-penalized criterion.
AB  - We consider a response adaptive design of clinical trials with a variance
      penalized criterion. It is shown that this criterion evaluates the performance of
      a response adaptive design based on both the number of patients assigned to the
      better treatment and the power of the statistical test. A new proportion of
      treatment allocation is proposed and the doubly biased coin procedure is used to
      target the proposed proportion. Under reasonable assumptions, the proposed design
      is demonstrated to generate an asymptotic variance of allocation proportions,
      which is smaller than that of the drop-the-loser design. Simulation comparisons
      of the proposed design with some existing designs are presented.

PMID- 19757433
TI  - Microchip CE analysis of amino acids on a titanium dioxide nanoparticles-coated
      PDMS microfluidic device with in-channel indirect amperometric detection.
AB  - In this paper, titanium dioxide nanoparticles (TiO(2) NPs) were employed to
      construct a functional film on PDMS microfluidic channel surface, which was
      formed by sequentially immobilizing poly(diallyldimethylammonium chloride) and
      TiO(2) NPs on PDMS surface by layer-by-layer assembly technique. The modified
      PDMS microchip exhibited a decreased and stable EOF, which was favorable for the
      separation of biomolecules with similar migration times. Arginine, phenylalanine,
      serine and threonine were used as model analytes to evaluate the performance of
      the modified microchip. The four amino acids were efficiently separated within
      100 s in a 3.7 cm long separation channel and successfully detected on the carbon
      fiber electrode in conjunction with in-channel indirect amperometry. Resolutions
      and theoretical plate numbers of the analytes were considerably enhanced in the
      presence of TiO(2) NPs. The modified microchip demonstrated excellent stability
      and reproducibility with improved RSDs of migration times and peak currents for
      run-to-run, day-to-day and chip-to-chip analyses, respectively. Variables
      influencing the separation efficiency and amperometric response, including
      injection and separation voltage, the working electrode position and buffer
      concentration, were optimized in detail.

PMID- 19757434
TI  - Design and adaptation of miniaturized electrochemical devices integrating carbon
      nanotube-based sensors to commercial CE equipment.
AB  - The design of new electrochemical devices integrating carbon nanotube sensors and
      their adaptation to commercial CE equipments are described. One of these designs
      was made for using commercial screen-printed electrodes, whereas the second was
      projected for coupling commercial glassy carbon electrodes. The electrochemical
      characterization of these devices revealed that their hydrodynamic behaviour is
      strongly influenced by the electrode modification with multi-wall carbon
      nanotubes that provided faster and/or more sensitive signals. The analytical
      applicability of these devices was illustrated for the CZE separation of
      chlorinated phenols and the MEKC separation of endocrine disruptors, where the
      use of carbon nanotube sensors has proved to be advantageous when compared with
      unmodified ones, with good electrocatalytic properties combined with acceptable
      background currents and a remarkable resistance to passivation.

PMID- 19757435
TI  - Study of acetylcholinesterase inhibitors using CE with contactless conductivity
      detection.
AB  - The hydrolysis of acetylcholine and acetylthiocholine as catalyzed by the enzyme
      acetylcholinesterase was monitored by CE with contactless conductivity detection
      by determining the acetate produced in the reaction. This approach eliminates the
      need for a color forming derivatization procedure. The effects of the three
      inhibitors galanthamine, hyperzine A and paraoxon on the enzyme kinetics could
      also be investigated by the new procedure and the IC(50) values were determined.
      The contactless conductivity detection was also found to be compatible with the
      electrophoretically mediated microanalyis approach, in which the enzymatic
      reaction is carried out directly inside the capillary prior to separation and
      quantification.

PMID- 19757436
TI  - A determination of submicromolar concentrations of glycine in periaqueductal gray
      matter microdialyzates using capillary zone electrophoresis with contactless
      conductivity detection.
AB  - CE with contactless conductivity detection has been used to determine the glycine
      neurotransmitter in periaqueductal gray matter (PAG) of rats. The LOD for glycine
      has been decreased to a value of 0.2 microM by adding 75% v/v of ACN to the
      samples and increasing the sample zone introduced to a value of 20% of the
      overall capillary length. The repeatabilities of the analyte migration times and
      the zone areas amount to 2.1 and 2.7%, respectively. The optimized CE/contactless
      conductivity detection method makes it possible to determine the micromolar
      concentrations of glycine in PAG microdialyzates without the necessity of sample
      derivatization. It follows from a pharmacological study that a local inflammation
      initiated by an application of carrageenan increased the glycine concentration in
      the rat PAG seven times, compared with a control. The glycine level in PAG can be
      decreased and the pain suppressed by administering paracetamol.

PMID- 19757437
TI  - A compact and high-resolution version of a capacitively coupled contactless
      conductivity detector.
AB  - An all-in-one version of a capacitively coupled contactless conductivity detector
      is introduced. The absence of moving parts (potentiometers and connectors) makes
      it compact (6.5 cm(3)) and robust. A local oscillator, working at 1.1 MHz, was
      optimized to use capillaries of id from 20 to 100 microm. Low noise circuitry and
      a high-resolution analog-to-digital converter (ADC) (21 bits effective) grant
      good sensitivities for capillaries and background electrolytes currently used in
      capillary electrophoresis. The fixed frequency and amplitude of the signal
      generator is a drawback that is compensated by the steady calibration curves for
      conductivity. Another advantage is the possibility of determining the inner
      diameter of a capillary by reading the ADC when air and subsequently water flow
      through the capillary. The difference of ADC reading may be converted into the
      inner diameter by a calibration curve. This feature is granted by the 21-bit ADC,
      which eliminates the necessity of baseline compensation by hardware. In a typical
      application, the limits of detection based on the 3sigma criterion (without
      baseline filtering) were 0.6, 0.4, 0.3, 0.5, 0.6, and 0.8 micromol/L for K(+),
      Ba(2+), Ca(2+), Na(+), Mg(2+), and Li(+), respectively, which is comparable to
      other high-quality implementations of a capacitively coupled contactless
      conductivity detector.

PMID- 19757438
TI  - B7-1/2, but not PD-L1/2 molecules, are required on IL-10-treated tolerogenic DC
      and DC-derived exosomes for in vivo function.
AB  - Costimulatory molecules, such as B7-1/2 and PD-L1/2 play an important role in the
      function of APC. The regulation of the surface levels of costimulatory molecules
      is one mechanism by which APC maintain the balance between tolerance and
      immunity. We examined the contributions of B7-1/2 and PD-L1/2 to the function of
      IL-10-treated, immunosuppressive DC as well as therapeutic exosomes derived from
      these DC. IL-10 treatment of DC significantly downregulated surface expression of
      MHC II, B7-1, B7-2, and decreased levels of MHC I and PD-L2. IL-10 treatment of
      DC resulted in a modified costimulatory profile of DC-secreted exosomes with a
      reduction in B7-1, PD-L1 and PD-L2. We further demonstrate that absence of B7-1
      or B7-2 on donor DC results in a loss of ability of IL-10-treated DC and their
      exosomes to suppress the delayed-type hypersensitivity response, whereas IL-10
      treated DC deficient in PD-L1/2 as well as their secreted exosomes retained the
      ability to suppress delayed-type hypersensitivity responses. We conclude that B7
      1 and B7-2, but not PD-L1 and PD-L2, on IL-10-treated DC and DC-derived exosomes
      play a critical role in immunosuppressive functions of both DC and exosomes.

PMID- 19757439
TI  - Antigen-dependent rescue of nose-associated lymphoid tissue (NALT) development
      independent of LTbetaR and CXCR5 signaling.
AB  - Nose-associated lymphoid tissue (NALT) in the rodent upper respiratory tract
      develops postnatally and is considered to be independent of several factors known
      to be involved in the organogenesis of LN and Peyer's patches (PP). In this study
      we demonstrate that at least two different pathways result in NALT development.
      Following NALT anlage formation the intrinsic pathway relies on a signaling
      cascade including those mediated through the chemokine receptor CXCR5 and the
      lymphotoxin beta receptor (LTbetaR). This allows for the formation of high
      endothelial venules and thereby the recruitment of lymphocytes into NALT.
      Alternatively, high endothelial venule formation and lymphocyte recruitment can
      be induced in the NALT anlage by environmental signals, which are independent of
      LT-betaR and chemokine receptor CXCR5 signaling but in part rely on CD40 ligand.
      Thus, our study identifies a novel mechanism that facilitates the rescue of NALT
      development at late stages in adult life independent of the canonical LTbetaR
      CXCR5 signaling axis.

PMID- 19757440
TI  - Myeloid-derived suppressor cells in inflammation: uncovering cell subsets with
      enhanced immunosuppressive functions.
AB  - Although originally described in tumor-bearing hosts, myeloid-derived suppressor
      cells (MDSC) have been detected under numerous pathological situations that cause
      enhanced demand of myeloid cells. Thus, MDSC might be part of a conserved
      response to different endogenous and exogenous stress signals, including
      inflammation. Two processes are fundamental for MDSC biology: differentiation
      from myeloid progenitors and full activation of their immune regulatory program
      by factors released from activated T cells or present in the microenvironment
      conditioned by either tumor growth or inflammation. How these two processes are
      controlled and linked is still an open question. In this issue of the European
      Journal of Immunology, a paper demonstrates that a combination of the known
      inflammatory molecules, IFN-gamma and LPS, sustains MDSC expansion and activation
      while suppressing differentiation of DC from bone marrow precursors. Moreover,
      this paper contributes to defining the cell subsets that possess immunoregulatory
      properties within the broad population of CD11b(+)Gr-1(+) cells, often altogether
      referred to as MDSC.

PMID- 19757441
TI  - Pharmacological targeting of CDK9 in cardiac hypertrophy.
AB  - Cardiac hypertrophy allows the heart to adapt to workload, but persistent or
      unphysiological stimulus can result in pump failure. Cardiac hypertrophy is
      characterized by an increase in the size of differentiated cardiac myocytes. At
      the molecular level, growth of cells is linked to intensive transcription and
      translation. Several cyclin-dependent kinases (CDKs) have been identified as
      principal regulators of transcription, and among these CDK9 is directly
      associated with cardiac hypertrophy. CDK9 phosphorylates the C-terminal domain of
      RNA polymerase II and thus stimulates the elongation phase of transcription.
      Chronic activation of CDK9 causes not only cardiac myocyte enlargement but also
      confers predisposition to heart failure. Due to the long interest of molecular
      oncologists and medicinal chemists in CDKs as potential targets of anticancer
      drugs, a portfolio of small-molecule inhibitors of CDK9 is available. Recent
      determination of CDK9's crystal structure now allows the development of selective
      inhibitors and their further optimization in terms of biochemical potency and
      selectivity. CDK9 may therefore constitute a novel target for drugs against
      cardiac hypertrophy.

PMID- 19757442
TI  - The impact of breast MRI on surgical decision-making: are patients at risk for
      mastectomy?
AB  - BACKGROUND AND OBJECTIVES: The goal of the current study was to determine whether
      MRI impacts multidisciplinary treatment planning and if it leads to increased
      mastectomy rates. METHODS: A retrospective review was conducted of 441 patients
      treated for breast cancer between January 2005 and May 2008 who underwent breast
      MRI. Data included number of additional findings and their imaging and pathologic
      work-up. This was analyzed to determine impact of MRI on treatment planning.
      RESULTS: Of 441 patients, 45% had > or =1 additional finding on MRI. Of 410
      patients with complete records, 29% had changes in the treatment plan, including
      36 patients who were initially considered for breast conservation but proceeded
      directly to mastectomy based on MRI findings of suspected multicentricity. Twenty
      three of those patients did not have a biopsy of the MRI lesion, with 87% having
      unicentric disease on final pathology. Overall, the mastectomy rate was 44%,
      which was significantly increased compared to patients not undergoing MRI (32%, P
      < 0.05). CONCLUSIONS: Breast MRI alters the treatment planning for many patients
      with newly diagnosed breast cancer. Mastectomy rates are increased when MRI
      results alone direct surgical planning. Biopsy of MRI-identified lesions should
      be performed to avoid over-treatment.

PMID- 19757443
TI  - Predictive factors of early relapse in UICC stage I-III colorectal cancer
      patients after curative resection.
AB  - BACKGROUND AND OBJECTIVES: To predict the clinicopathologic factors for early
      relapse of UICC stage I-III colorectal cancer (CRC) patients undergoing curative
      resection and thus to identify a subgroup of patients who are at high risk for
      postoperative early relapse. METHODS: Between January 2001 and June 2007, a total
      of 778 UICC stage I-III CRC patients who underwent a radical resection and
      regular follow-up were retrospectively analyzed. Of these 778 CRC patients, 521
      colon cancer and 257 rectal cancer cases were analyzed, respectively, to
      determine the predictors of early relapse postoperatively. These 778 patients
      were followed-up intensively, and their outcomes were investigated
      retrospectively. RESULTS: Out of 521 colon cancer patients, postoperative relapse
      after primary resection was found in 142 (27.3%) patients, and 77 (54.2%) of 142
      recurrent colon cancer patients were classified as postoperative early relapse.
      Meanwhile, among 257 rectal cancer patients, postoperative relapse was found in
      68 (26.5%) patients and 44 (64.7%) of 68 recurrent rectal cancer patients were
      identified as postoperative early relapse. Forty-nine (63.6%) of 77 early
      relapsed colon cancer patients were stage III, and likewise, 26 (59.1%) of 44
      early relapsed rectal cancer patients were stage III. Univariately, postoperative
      early relapse of colon cancer patients was significantly correlated with the
      presence of vascular invasion (P < 0.001), perineural invasion (P < 0.001), high
      postoperative carcinoembryonic antigen (CEA) level (P = 0.001), and type of
      surgery (P = 0.016). Using a Cox proportional hazards analysis, the presence of
      vascular invasion (P = 0.033), perineural invasion (P = 0.005), and high
      postoperative CEA levels (P = 0.001) were demonstrated to be independent
      predictors of postoperative early relapse of colon cancer patients, while in
      rectal cancer patients, both vascular invasion (P = 0.039) and perineural
      invasion (P = 0.008) were statistically significant predictors of early relapse
      by univariate analysis. Using a Cox proportional hazards analysis, only
      perineural invasion (P = 0.043) was an independent factor. Early relapse cases
      had significant lower overall survival rates than non-early relapse cases either
      in colon cancer (P < 0.001) or in rectal cancer (P = 0.0091) patients.
      CONCLUSIONS: This study suggests that vascular invasion, perineural invasion, and
      postoperative CEA level may be significant factors for postoperative early
      relapse of colon cancer; while only perineural invasion is considered to be a
      significant predictor in rectal cancer patients. Identification of these high
      risk UICC stage I-III CRC patients of early relapse is important, and thus could
      help to define patients with this tumor entity for an enhanced follow-up and
      therapeutic program.

PMID- 19757444
TI  - Balance diagnostics for comparing the distribution of baseline covariates between
      treatment groups in propensity-score matched samples.
AB  - The propensity score is a subject's probability of treatment, conditional on
      observed baseline covariates. Conditional on the true propensity score, treated
      and untreated subjects have similar distributions of observed baseline
      covariates. Propensity-score matching is a popular method of using the propensity
      score in the medical literature. Using this approach, matched sets of treated and
      untreated subjects with similar values of the propensity score are formed.
      Inferences about treatment effect made using propensity-score matching are valid
      only if, in the matched sample, treated and untreated subjects have similar
      distributions of measured baseline covariates. In this paper we discuss the
      following methods for assessing whether the propensity score model has been
      correctly specified: comparing means and prevalences of baseline characteristics
      using standardized differences; ratios comparing the variance of continuous
      covariates between treated and untreated subjects; comparison of higher order
      moments and interactions; five-number summaries; and graphical methods such as
      quantile-quantile plots, side-by-side boxplots, and non-parametric density plots
      for comparing the distribution of baseline covariates between treatment groups.
      We describe methods to determine the sampling distribution of the standardized
      difference when the true standardized difference is equal to zero, thereby
      allowing one to determine the range of standardized differences that are
      plausible with the propensity score model having been correctly specified. We
      highlight the limitations of some previously used methods for assessing the
      adequacy of the specification of the propensity-score model. In particular,
      methods based on comparing the distribution of the estimated propensity score
      between treated and untreated subjects are uninformative.

PMID- 19757445
TI  - Correction for misclassification of a categorized exposure in binary regression
      using replication data.
AB  - Continuous epidemiologic exposure data are often categorized according to one or
      more cut points before inclusion in a regression analysis involving some outcome
      variable. If the original data are subject to measurement error, the categorized
      data will be afflicted with misclassification, which is differential, and which
      induces biases in naive methods that ignore the misclassification. We propose a
      method for measurement error adjustment in these settings, when there are
      replicate data available on the original measurements, and when the outcome
      variable is dichotomous. Working on the continuous measurements, conditional
      densities of the exposure given the outcome are estimated and used to obtain odds
      ratios. The estimation of densities is done either parametrically or
      nonparametrically. The method is compared with the naive approach of simply
      categorizing the erroneous mean measurements in simulation studies, and although
      the nonparametric method is more variable, it has the best overall performance,
      the greatest differences being observed in settings where the effects and/or the
      measurement errors are large. The performance of the parametric method is highly
      dependent on the model fit. Applying the methods to a real-life data set from the
      Framingham Heart Study produced larger estimated odds ratios for coronary heart
      disease as a result of elevated systolic blood pressure, as compared with naive
      odds ratios. We provide some discussion of alternative procedures that might be
      considered including regression calibration, SIMEX and the use of estimated
      misclassification probabilities.

PMID- 19757446
TI  - Developments in asbestos cancer risk assessment.
AB  - BACKGROUND: Efforts have been made for 25 years to develop asbestos risk
      assessments that provide valid information about workplace and community cancer
      risks. Mathematical models have been applied to a group of workplace epidemiology
      studies to describe the relationships between exposure and risk. EPA's most
      recent proposed method was presented at a public meeting in July 2008. METHODS:
      Risk assessments prepared by USEPA, OSHA, and NIOSH since 1972 were reviewed,
      along with related literature. RESULTS AND CONCLUSIONS: None of the efforts to
      use statistical models to characterize relative cancer potencies for asbestos
      fiber types and sizes have been able to overcome limitations of the exposure
      data. Resulting uncertainties have been so great that these estimates should not
      be used to drive occupational and environmental health policy. The EPA has now
      rejected and discontinued work on its proposed methods for estimating potency
      factors. Future efforts will require new methods and more precise and reliable
      exposure assessments. However, while there may be genuine need for such work, a
      more pressing priority with regard to the six regulated forms of asbestos and
      other asbestiform fibers is to ban their production and use.

PMID- 19757447
TI  - Advantages of compound-specific stable isotope measurements over bulk
      measurements in studies on plant uptake of intact amino acids.
AB  - Increasing interest in the ability of plants to take up amino acids has given
      rise to questions on the accuracy of the commonly used bulk method to measure and
      calculate amino acid uptake. This method uses bulk measurements of 13C and 15N
      enrichment in plant tissues after application of dual-labelled amino acids but
      some authors have recommended the use of compound-specific stable isotope (CSI)
      analysis of the plants' amino acids instead. However, there has never been a
      direct evaluation of both methods. We conducted a field study applying dual
      labelled (13C, 15N) amino acids (glycine, valine, tyrosine and lysine) to soil of
      a Plantago lanceolata monoculture. Root and shoot samples were collected 24 h
      after label application and the isotope composition of the plant tissues was
      investigated using bulk and CSI measurements. Enrichment of 13C in the case of
      CSI measurements was limited to the applied amino acids, showing that no
      additional 13C had been incorporated into the plants' amino acid pool via the
      uptake of tracer-derived C-fragments. Compared with this rather conservative
      indicator of amino acid uptake, the 13C enrichment of bulk measurements was 8, 5,
      1.6 and 6 times higher for fine roots, storage roots, shoot and the whole plant,
      respectively. These findings show that the additional uptake of tracer-derived C
      fragments will result in a considerable overestimation of amino acid uptake in
      the case of bulk measurements. We therefore highly recommend the use of CSI
      measurements for future amino acid uptake studies due to their higher accuracy.

PMID- 19757448
TI  - Functionalized pyrolytic highly oriented graphite polymer film for surface
      assisted laser desorption/ionization mass spectrometry in environmental analysis.
AB  - The pyrolytic highly oriented graphite polymer film (PGS) was first employed to
      analyze low-mass analytes in environmental analysis by surface-assisted laser
      desorption/ionization mass spectrometry (SALDI-MS). PGS is a synthetic uniform
      and highly oriented graphite polymer film with high thermal anisotropic
      conductivity. We have found that negative ion mode SALDI-MS using oxidized PGS
      (PGS-SALDI-MS) can be used to detect [M-H]- ions from perfluorooctanoic acid
      (PFOA) and other perfluoroalkylcarboxylic acids when the PGS surface is modified
      with the cationic polymer polyethyleneimine (PEI). The signal intensity of PFOA
      when employing the PEI modification showed a ten-fold increase over that obtained
      from desorption/ionization on porous silicon (DIOS). PFOA was quantified using
      PGS-SALDI-MS and the calibration curve showed a wide linear dynamic range of
      response (20-1000 ppb). The combination of atmospheric pressure ionization and
      PGS (AP-PGS-SALDI) showed greater signal intensity than vacuum PGS-SALDI for
      deprotonated PFOA. Several other environmentally important chemicals, including
      perfluoroalkylsulfonic acid, pentachlorophenol, bisphenol A, 4-hydroxy-2
      chlorobiphenyl, and benzo[a]pyrene, were also successfully used to evaluate PGS
      SALDI-MS. In addition, we found that nonafluoro-1-butanesulfonic acid was able to
      produce protonated peptides in positive ion PGS-SALDI-MS, but that
      perfluoropentanoic acid and trifluoroacetic acid were not. It is suggested that
      perfluoroalkylsulfonic acids are better protonating agents than
      perfluoroalkylcarboxylic acids in SALDI-MS.

PMID- 19757449
TI  - Derivatization aids in the determination of end groups in poly(alkylene glycol)s
      by matrix-assisted laser desorption/ionization mass spectrometry.
AB  - A method for end-group characterization by matrix-assisted laser
      desorption/ionization (MALDI) mass spectrometry following preliminary
      derivatization with N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) and
      capryloyl chloride is described and applied to poly(alkylene glycol)s. The MALDI
      mass spectra of the products revealed peaks of sodiated derivative cations, whose
      shift by the respective increments allowed the determination of the number of end
      functional groups with active hydrogens. This approach is particularly efficient
      for the distinction of cyclic and linear dehydration products among minor
      components.

PMID- 19757450
TI  - Molecular depth profiling of multilayer structures of organic semiconductor
      materials by secondary ion mass spectrometry with large argon cluster ion beams.
AB  - In this study, we present molecular depth profiling of multilayer structures
      composed of organic semiconductor materials such as tris(8
      hydroxyquinoline)aluminum (Alq3) and 4,4'-bis[N-(1-naphthyl)-N
      phenylamino]biphenyl (NPD). Molecular ions produced from Alq3 and NPD were
      measured by linear-type time-of-flight (TOF) mass spectrometry under 5.5 keV
      Ar70) ion bombardment. The organic multilayer films were analyzed and etched with
      large Ar cluster ion beams, and the interfaces between the organic layers were
      clearly distinguished. The effect of temperature on the diffusion of these
      materials was also investigated by the depth profiling analysis with Ar cluster
      ion beams. The thermal diffusion behavior was found to depend on the specific
      materials, and the diffusion of Alq3 molecules was observed to start at a lower
      temperature than that of NPD molecules. These results prove the great potential
      of large gas cluster ion beams for molecular depth profiling of organic
      multilayer samples.

PMID- 19757451
TI  - Extending matrix-assisted laser desorption/ionization triple quadrupole mass
      spectrometry enzyme screening assays to targets with small molecule substrates.
AB  - Mass spectrometry (MS)-based high-throughput screening (HTS) has tremendous
      potential as an alternative to current screening methods due to its speed,
      sensitivity, reproducibility and label-free readout. We recently reported that a
      new generation matrix-assisted laser desorption/ionization triple quadrupole
      (MALDI-QqQ) mass spectrometer is ideally suited for a variety of enzyme assays
      and screening protocols. However, all the targets measured to date had peptide
      substrates that were easily monitored by selected ion monitoring (SIM) without
      interference from the MALDI matrix. To further extend the application to enzymes
      with small molecule, non-peptide substrates, we evaluated this method for
      measuring enzyme activity and inhibition of acetylcholinesterase (AChE). Due to
      the potential of MALDI matrix interference, multiple reaction monitoring (MRM)
      was investigated for selective MS/MS transitions and to accurately measure the
      conversion of acetylcholine into choline. Importantly, ionization, detection and
      MRM transition efficiency differences between the substrate and product can be
      overcome by pre-balancing the MRM transitions during method development, thus
      allowing for a direct readout of the enzyme activity using the ratio of the
      substrate and product signals. Further validation of the assay showed accurate
      concentration-dependent inhibition measurements of AChE with several known
      inhibitors. Finally, a small library of 1008 drug-like compounds was screened at
      a single dose (10 microM) and the top 10 inhibitors from this primary screen were
      validated in a secondary screen to determine the rank order of inhibitory potency
      for each compound. Collectively, these data demonstrate that a MALDI-QqQMS-based
      readout platform is amenable to measuring small molecule substrates and products
      and offers significant advantages over current HTS methods in terms of speed,
      sensitivity, reproducibility and reagent costs.

PMID- 19757452
TI  - Determination of rare earth elements in tomato plants by inductively coupled
      plasma mass spectrometry techniques.
AB  - In recent years identification of the geographical origin of food has grown more
      important as consumers have become interested in knowing the provenance of the
      food that they purchase and eat. Certification schemes and labels have thus been
      developed to protect consumers and genuine producers from the improper use of
      popular brand names or renowned geographical origins. As the tomato is one of the
      major components of what is considered to be the healthy Mediterranean diet, it
      is important to be able to determine the geographical origin of tomatoes and
      tomato-based products such as tomato sauce. The aim of this work is to develop an
      analytical method to determine rare earth elements (RRE) for the control of the
      geographic origin of tomatoes. The content of REE in tomato plant samples
      collected from an agricultural area in Piacenza, Italy, was determined, using
      four different digestion procedures with and without HF. Microwave dissolution
      with HNO3 + H2O2 proved to be the most suitable digestion procedure. Inductively
      coupled plasma quadrupole mass spectrometry (ICPQMS) and inductively coupled
      plasma sector field plasma mass spectrometry (ICPSFMS) instruments, both coupled
      with a desolvation system, were used to determine the REE in tomato plants in two
      different laboratories. A matched calibration curve method was used for the
      quantification of the analytes. The detection limits (MDLs) of the method ranged
      from 0.03 ng g(-1) for Ho, Tm, and Lu to 2 ng g(-1) for La and Ce. The precision,
      in terms of relative standard deviation on six replicates, was good, with values
      ranging, on average, from 6.0% for LREE (light rare earth elements) to 16.5% for
      HREE (heavy rare earth elements). These detection limits allowed the
      determination of the very low concentrations of REE present in tomato berries.
      For the concentrations of REE in tomato plants, the following trend was observed:
      roots > leaves > stems > berries.

PMID- 19757453
TI  - Determination of cylindrospermopsin in freshwaters and fish tissue by liquid
      chromatography coupled to electrospray ion trap mass spectrometry.
AB  - Cylindrospermopsin (CYN) is a toxic alkaloid-like compound produced by some
      strains of cyanobacteria, procariotic organisms occurring in water blooms,
      observed worldwide in eutrophic lakes and drinking water reservoirs. Methods for
      determination of CYN in freshwater and fish muscle by liquid chromatography
      coupled to electrospray ion trap mass spectrometry are herein described. The
      performances of both methods are reported; ion trap LC/ESI-MS/MS resulted highly
      selective and reliable in unambiguous identification of CYN, based on monitoring
      the precursor ion and three product ions. The methods developed showed
      satisfactory mean recoveries (higher than 63.6%) and relative standard
      deviations, ranging from 5.8 to 9.8%. The limits of quantification at 0.10 ng/mL
      in freshwaters and 1.0 ng/g in fish muscle, respectively, allow for determination
      of CYN also in early contamination stages. Ion trap LC/ESI-MS/MS was successfully
      applied to the identification and quantification of CYN in water and
      cyanobacteria extracts from Lake Averno, near Naples, representing the first case
      of contamination described in southern Italy.

PMID- 19757454
TI  - Efficient adenovirus-mediated gene transfer to gastric tissue by oral
      administration.
AB  - BACKGROUND: Recombinant adenoviruses (rAd) are well-characterized viral vectors
      and have been studied in many human diseases. However, there are no detailed
      methods for transferring genes to the stomach using rAd. METHODS: Gastric
      epithelial cells were infected with rAd encoding green fluorescence protein
      (AdGFP) for different times, or with AdGFP that had been incubated in artificial
      gastric juice at different pH values for 1 h. Gene expression was detected by
      fluorescence microscope and flow cytometry. Mice were infected via oral
      administration with rAd encoding red fluorescence protein and beta-galactosidase
      (AdRFP-lacZ) or rAd encoding mouse interleukin-17 (AdmIL-17), and tissues were
      collected at the indicated times after infection. LacZ expression in different
      tissues was detected by X-gal staining and IL-17 expression in the stomach was
      assessed by the real-time polymerase chain reaction and an enzyme-linked
      immunosorbent assay. Inflammation in the stomach was also assessed. RESULTS: rAd
      could infect the gastric epithelial cells and tolerate pH 5 for 1 h in vitro.
      Adenovirus-mediated genes were specifically expressed in the gastrointestinal
      tract and transgene expression persisted in gastric tissue for up to 7 days after
      oral administration of AdRFP-lacZ. Oral administration of AdmIL-17 induced mIL-17
      expression in gastric tissue at the mRNA and protein levels and protein level
      peaked on day 5 post-infection. IL-6, a target protein of IL-17, and gastric
      inflammation also increased in AdmIL-17-infected mice. CONCLUSIONS: The present
      study has established a detailed method for transferring adenovirus-mediated gene
      to the stomach, which may provide a valuable approach for gene therapy or the
      study of the basic biology of gastric diseases.

PMID- 19757455
TI  - Evaluation of the muscle gene transfer activity of a series of amphiphilic
      triblock copolymers.
AB  - BACKGROUND: Amphiphilic triblock copolymers such as the polyethylene oxide
      polypropylene oxide-polyethylene oxide L64 (PEO(13)-PPO(30)-PEO(13))
      significantly increase transgene expression after injection of DNA/polymer
      mixtures into skeletal muscles. To better understand the way such copolymers act,
      we studied the behaviour of different poloxamers, including L64, both in vitro
      and in vivo. METHODS: The in vitro and in vivo transfection activity of five
      copolymers that differ either by their molecular weight or by their
      hydrophilic/hydrophobic balance was evaluated. Furthermore, we also studied the
      membrane permeabilizing properties of the poloxamers. RESULTS: The results
      obtained indicate that, after intramuscular administration of DNA/poloxamer
      formulations, all five compounds were able to significantly increase the
      expression levels of luciferase compared to an injection of naked DNA. Using a
      LacZ expression cassette, up to 30% of the muscle fibers expressed the reporter
      gene. Furthermore, we show that the effect can be obtained using different
      promoters. Finally, we document that, to some extent, all five poloxamers possess
      membrane permeabilizing properties. CONCLUSIONS: Taken together, the results
      obtained in the present study show that there is a large flexibility in terms of
      molecular weight and EO/PO ratio for obtaining increased levels of transgene
      expression in vivo.

PMID- 19757456
TI  - Olfactory guidance of nipple attachment and suckling in kittens of the domestic
      cat: Inborn and learned responses.
AB  - In 60 kittens (11 litters) from free-ranging domestic cats we investigated the
      role of chemical cues in facilitating nipple attachment and suckling during the
      first month of postnatal life when kittens are totally dependent on the mother's
      milk. Kittens were tested both together and individually on sedated females in
      different reproductive states. We found (1) that newborn kittens with no suckling
      experience responded to the ventrum of lactating but not to the ventrum of
      nonlactating females with search behavior and attached to nipples within minutes;
      (2) that even in older kittens, nipple attachment depended on females'
      reproductive state, with virtually no attachments on nonreproducing females, some
      on pregnant females, the greatest number on early-lactating females, followed by
      a decline on late-lactating females; and (3) that kittens could locate their
      particular, most used nipple on their mother but not on a female of similar
      lactational age, even after eye opening. We suggest that kittens respond from
      birth with efficient nipple-search behavior to inborn olfactory cues on the
      mother's ventrum, that emission of these is under hormonal control, but that
      kittens also quickly learn olfactory cues specific to their own mother and to
      their own particular nipples.

PMID- 19757457
TI  - Sexually dimorphic effects of postnatal treatment on the development of activity
      based anorexia in adolescent and adult rats.
AB  - Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis is a marked
      feature of anorexia nervosa. Using a modified version of the activity-based
      animal model of anorexia nervosa, we examine whether factors known to affect HPA
      axis activity influence the development of activity-based anorexia (ABA). Male
      and female rats were subjected to maternal separation or handling procedures
      during the first two postnatal weeks and tested in a mild version of the ABA
      paradigm, comprised of 2-hr daily running wheel access followed by 1-hr food
      access, either in adolescence or adulthood. Compared to handled females,
      maternally separated females demonstrated greater increases in wheel running and
      a more pronounced running-induced suppression of food intake during adolescence,
      but not in adulthood. In contrast, it was only in adulthood that wheel running
      produced more prolonged anorexic effects in maternally separated than in handled
      males. These findings highlight the interplay between early postnatal treatment,
      sex of the animal, and developmental age on running, food intake, and rate of
      body weight loss in a mild version of the ABA paradigm.

PMID- 19757458
TI  - What we don't know can, and will, hurt us: thinking about what is not known is a
      crucial feature of science that needs defending.

PMID- 19757459
TI  - Humans as second orangutans: sense or nonsense?: a reminder of what the molecular
      data indicate, and why they can't be ignored or dismissed.

PMID- 19757463
TI  - Applications of protein biochips in biomedical and biotechnological research.
AB  - Progress in the development of protein-immobilization strategies and methods has
      made protein biochips increasingly accessible. The integration of these assay and
      analysis platforms into biomedical and biotechnological research has
      substantially expanded the repertoire of methods available for proteomics and
      biomarker research and for drug development. This Minireview highlights selected
      developments in the application of protein biochips in these fields.

PMID- 19757464
TI  - Cardiosulfa, a small molecule that induces abnormal heart development in
      zebrafish, and its biological implications.

PMID- 19757465
TI  - Coating nanocrystals with amphiphilic thermosensitive copolymers.

PMID- 19757466
TI  - A metal-collagen peptide framework for three-dimensional cell culture.

PMID- 19757467
TI  - Hydroxy oximes as organophosphorus nerve agent sensors.

PMID- 19757468
TI  - Propene epoxidation with dioxygen catalyzed by gold clusters.

PMID- 19757469
TI  - Liquid-crystalline triangle honeycomb formed by a dithiophene-based X-shaped
      bolaamphiphile.

PMID- 19757470
TI  - [O-NSR]TiCl3-catalyzed copolymerization of ethylene with functionalized olefins.

PMID- 19757471
TI  - pH-switchable helicity of DNA-templated assemblies.

PMID- 19757472
TI  - Exploiting tautomerism for switching and signaling.

PMID- 19757473
TI  - Et2SBrSbCl5Br: an effective reagent for direct bromonium-induced polyene
      cyclizations.

PMID- 19757476
TI  - Benzenesulfonamidoquinolino-beta-cyclodextrin as a cell-impermeable fluorescent
      sensor for Zn2+.
AB  - A water-soluble benzenesulfonamidoquinolino-beta-cyclodextrin has been
      successfully synthesized in 30% yield by incorporating a N-(8-quinolyl)-p
      aminobenzenesulfonamide (HQAS) group to beta-cyclodextrin through a flexible
      linker. This compound exhibits a good fluorescence response in the presence of
      Zn2+ in water but gives poor fluorescence responses with other metal ions
      commonly present in a physiological environment under similar conditions.
      Fluorescence microscopic and two-dimensional NMR experiments showed that
      benzenesulfonamidoquinolino-beta-cyclodextrin could bind to the loose bilayer
      membranes. As a result, benzenesulfonamidoquinolino-beta-cyclodextrin was found
      to act as an efficient cell-impermeable Zn2+ probe, showing a specific
      fluorescent sensing ability to Zn2+-containing damaged cells whilst exhibiting no
      response in the presence of healthy cells.

PMID- 19757477
TI  - Consecutive formation of G-quadruplexes in human telomeric-overhang DNA: a
      protective capping structure for telomere ends.

PMID- 19757478
TI  - The effect of experimental conditions on the detection of spermine in cell
      extracts and tissues.
AB  - The aim of this work was to investigate the effect of experimental conditions on
      the visibility of polyamines. In solution the chemical shift of the three groups
      of peaks (at approximately 1.8, 2.1 and 3.1 ppm) were found to be pH dependent.
      Relaxation times in aqueous solution at pH 7.0, 298 K and 11.74 T were measured
      to be: putrescine (T(1) = 2.49 s, T(2) = 2.07 s), spermidine (T(1) = 1.27 s, T(2)
      = 1.05 s) and spermine (T(1) = 1.02 s, T(2) = 0.82 s). Simple spin-echo sequences
      could not be used to measure T(2) as the spins also experience phase evolution
      from homonuclear coupling which imposes a modulation on the T(2) decay curve.
      This modulation is eliminated by using CPMG sequences with an echo spacing of
      <500 micros. Relaxation times for spermine in solution in presence of metal ions
      and protein showed that metal ions had little effect on T(2); however, addition
      of 15 mg/ml bovine serum albumin reduced T(2) of spermine (0.41 s at 298 K and
      0.19 s at 277 K) but was not as short as the T(2) of the polyamine peak in
      prostatic tissue (0.03 s at 277 K). The MR visibility of polyamines in prostate
      cell extracts, PC-3 xenograft (intact as well as extracted) and intact human
      prostatic tissues were investigated. Polyamines were not detected in
      methanol/chloroform extracts, but were visible in perchloric acid extracts of
      prostate tumour cells. No polyamines were detected in the HR MAS spectra of three
      samples of whole PC-3 xenograft tissue studied. In summary, the chemical shift of
      polyamine species is pH dependent, while protein binding causes peak broadening
      and reduction in T(2). Perchloric acid extraction improves visibility of
      intracellular polyamines, but whole tissue polyamines are not seen in xenografts
      without epithelial/ ductal structure.

PMID- 19757479
TI  - Efficient gene delivery into mammalian cells by recombinant baculovirus
      containing a hybrid cytomegalovirus promoter/Semliki Forest virus replicon.
AB  - BACKGROUND: Baculovirus, which is widely utilized as an excellent tool for the
      production of recombinant protein in insect cells, has recently emerged as a
      novel and attractive gene delivery vehicle for mammalian cells. Alphavirus, such
      as Semliki Forest virus (SFV), has also received considerable attention for use
      as expression vectors because of its self-replicating property. In the present
      study, we investigated the characterization of recombinant baculovirus
      incorporating a hybrid cytomegalovirus (CMV) promoter/SFV replicon. METHODS:
      Recombinant baculovirus containing the hybrid CMV promoter/SFV replicon was
      constructed. Using enhanced green fluorescence protein (EGFP) as the reporter
      gene, gene delivery efficiencies and the ability to express heterogenous protein
      in mammalian cells were evaluated. Optimal transduction conditions, including
      transduction temperature, time and dose, were also investigated. RESULTS: The
      obtained recombinant baculovirus, Bac-CMV/SFV-EGFP, exhibited high transduction
      efficiency and high-level expression of reporter protein in mammalian cells.
      Furthermore, this recombinant baculovirus could induce apoptosis in mammalian
      cells in the course of transduction, as demonstrated by the observed DNA
      laddering patterns and increased caspase-3 activity. CONCLUSIONS: The developed
      baculovirus vector has a high transduction efficiency and the ability to mediate
      foreign gene expression in mammalian cells. Taken together with its pro-apoptotic
      properties, this baculovirus vector may provide an alternative tool for vaccine
      development.

PMID- 19757481
TI  - Differential efficacy of three commonly used pyrethroids against laboratory and
      field-collected larvae and adults of Helicoverpa zea (Lepidoptera: Noctuidae) and
      significance for pyrethroid resistance management.
AB  - BACKGROUND: Helicoverpa zea (Boddie) pyrethroid resistance monitoring programs
      typically utilize cypermethrin in the adult vial test. Here we investigated if
      differences in insect growth stage and pyrethroid structure affect resistance
      ratios and discuss implications for pyrethroid resistance management. RESULTS:
      Vial bioassays with cypermethrin, esfenvalerate and bifenthrin were conducted on
      H. zea third instars and male moths from a susceptible laboratory colony and the
      F1 generation of a pyrethroid-resistant field population. In the susceptible
      population, both growth stages were most sensitive to bifenthrin and adults were
      more sensitive to esfenvalerate than cypermethrin. LC(50) resistance ratios for
      the larvae and adults of the resistant population were approximately two times
      higher for bifenthrin than cypermethrin or esfenvalerate. CONCLUSION: For the
      resistant population, vial assays using either growth stage gave similar
      resistance ratios for each of the three pyrethroids, respectively, proving the
      adult vial test accurately reflects larval resistance. However, as resistance
      ratios varied considerably depending on the pyrethroid used, resistance ratio
      values obtained with one pyrethroid may not be predictive of resistance ratios
      for other pyrethroids. Our results suggest that carefully chosen pyrethroid
      structures diagnostic for specific mechanisms of resistance could improve
      regional monitoring programs.

PMID- 19757480
TI  - Heritability of depressive symptoms: a case study using a multilevel approach.
AB  - We present a case study using a multilevel modeling approach to determine whether
      depressive symptoms are affected by genetic factors. Existing studies examining
      this question have focused on twins. The present study built on the literature by
      conducting a preliminary study of the heritability of depressive symptoms within
      extended families. At the same time, this study assessed the need for adjustment
      of a heritability measure in a family study using a multigenerational sample. The
      sample consisted of 230 community-dwelling extended families that included 431
      adult offspring, comprising full siblings, half siblings and cousins that
      participated in the University of Southern California Longitudinal Study of
      Generations. All participants filled out the Center for Epidemiologic Studies
      Depression (CES-D) scale. The multilevel analysis allowed us to model the natural
      hierarchy of the extended family. Results indicate that the proportion of the
      phenotypic variance for CES-D that occurs due to genetic differences is not
      significantly larger than zero among these participants [h(2) = 8.6%, 95%
      confidence interval (CI) = 0-57%, p = 0.71]. Our findings suggest that future
      studies examining depressive symptoms in this sample can focus on non-genetic
      explanatory factors without the necessity to control for genetic variation.
      However, our study may be limited by measurement of prevalent depressive
      symptoms, which may not generalize to lifetime depressive symptoms.

PMID- 19757482
TI  - Developmental plasticity, modularity, and heterochrony during the phylotypic
      stage of the zebra fish, Danio rerio.
AB  - We studied early embryonic development of zebra fish and tested if changes in the
      external raising conditions could elicit phenotypic changes during the phylotypic
      stage which, classically, is considered as a conserved embryonic stage. In
      particular, we tested for internal constraints, plasticity, and heterochrony
      during the early embryonic development. Our tested hypotheses predict (i) no
      change associated with developmental stability/internal constraints, (ii) change
      of the rate of development associated with developmental flexibility, and (iii)
      heterochronic disruption of developmental pattern associated with a modular
      organization of the embryo. We measured 14 traits of embryos raised in different
      conditions (temperature, salinity, oxygen concentration). The results of our
      study show that zebra fish embryos respond flexibly to changes in external
      parameters even during the conserved "phylotypic stage." It also showed that
      internal constraints canalize early development when exposed to moderate external
      challenges. Hypoxic conditions, however, elicited a heterochronic delay of the
      onset of the development of the Anlagen of the eye and the otic vesicle from the
      remaining embryo. Therefore, we concluded that the eye and the otic vesicle are
      modules that may develop, to a certain degree, independently of the rest of the
      embryo. Because these modules become recognizable only under specific raising
      conditions, we suggest that the modularization acts as buffering mechanism
      against extreme developmental deviations. Our results provide support to the idea
      that modularity is present during the phylotypic stage, but it is not effective
      under normal conditions.

PMID- 19757483
TI  - Constant time gradient HSQC-iDOSY: practical aspects.
AB  - An improved constant time gradient HSQC-iDOSY pulse sequence is presented, and
      the corresponding form of the Stejskal-Tanner equation is derived. The pulse
      sequence is particularly well suited to the problem of analysing mixtures of
      chemically cognate species, where the high spectral resolution afforded by 1H-13C
      correlation methods is needed for DOSY experiments to give good diffusion
      resolution. Its use is illustrated for a mixture of rutin and its aglycone
      quercetin.

PMID- 19757484
TI  - Missing values in longitudinal dietary data: a multiple imputation approach based
      on a fully conditional specification.
AB  - Multiple imputation (MI) has increasingly received attention as a flexible tool
      to resolve missing data problems both in observational and controlled studies.
      Our goal has been to develop a valid and efficient MI procedure for the Diabetes
      Prediction and Prevention Nutrition Study, in which the diet of a cohort of
      newborn children with HLA-DQB1-conferred susceptibility to type 1 diabetes is
      repeatedly measured by 3-day food records over early childhood. The estimation of
      risk is based on a nested case-control design setup within the cohort. We have
      used an iterative procedure known as the fully conditional specification (FCS) to
      generate appropriate values for the missing dietary data, here playing the role
      of time-dependent covariates. Our method extends the standard FCS to repeated
      measurements settings with the possibility of non-monotone missingness patterns
      by being doubly iterative over the follow-up time of the individuals. In
      addition, our proposed procedure is nonparametric in the sense that the variables
      can have distributions deviating strongly from normality: it makes use of
      quantile normal scores to transform to normality, performs imputations, and
      transforms back to the original scale. By the use of a moving time window and
      stepwise regression procedures, the two-fold FCS method operates well with a
      great number of variables each measured repeatedly over time. Extensive
      simulation studies demonstrate that the procedure together with the proposed
      transformations and variable selection methods provides tools for valid and
      efficient statistical inference in the nested case-control setting, and its
      applications extend beyond that.

PMID- 19757485
TI  - Targeting of plasmid DNA-lipoplexes to cells with molecules anchored via a metal
      chelator lipid.
AB  - BACKGROUND: The ability to deliver plasmid DNA (pDNA) to specific cells in vivo
      is crucial for achieving efficient targeted transfection with nonviral vectors.
      We previously used stealth liposomes containing the chelator lipid
      3(nitrilotriacetic acid)-ditetradecylamine (NTA(3)-DTDA) to target delivery of
      antigen and cytokines to immune cells in vivo. In the present study, we utilized
      liposomes containing NTA(3)-DTDA and the ionizable aminolipid 1,2-dioleoyl-3
      dimethyl-ammonium-propane (DODAP) to incorporate pDNA into complexes for
      targeting to cells. METHODS: Liposomes containing DODAP, NTA(3)-DTDA and helper
      lipids were acidified (pH 5.5) and mixed with pDNA to form complexes. These
      lipoplexes were neutralized and engrafted with His-tagged molecules for targeting
      to extracellular receptors. Targeted transfection efficiency was assessed using
      the enhanced green fluorescent protein reporter gene. RESULTS: Initial
      transfections of HEK-293 cells using a His-tagged peptide (T2) related to the Arg
      rich motif of HIV-1 TAT protein resulted in a low transfection efficiency
      (<2.5%). Optimization of the lipid formulation and use of an endosome
      destabilizing peptide and inhibitor of DNase II, increased transfection
      approximately 20-fold. These lipoplexes are approximately 250 nm in diameter, and
      transfection efficiencies were: approximately 50% for HEK-293 cells targeted with
      lipoplexes containing pEGFP-N1 and engrafted with T2, and 30-40% for HepG2 cells
      targeted with lipoplexes engrafted with a peptide specific for the VEGF receptor
      Flt-1. CONCLUSIONS: The results show that DODAP-containing lipoplexes
      incorporating NTA(3)-DTDA enable the engraftment of targeting molecules and the
      effective targeting of pDNA to cells in serum-containing media, resulting in
      efficient transgene expression. The strategy may provide a convenient approach
      for targeting pDNA to cells in vivo in therapeutic applications.

PMID- 19757486
TI  - Quadratic inference functions in marginal models for longitudinal data.
AB  - The quadratic inference function (QIF) is a new statistical methodology developed
      for the estimation and inference in longitudinal data analysis using marginal
      models. This method is an alternative to the popular generalized estimating
      equations approach, and it has several useful properties such as robustness, a
      goodness-of-fit test and model selection. This paper presents an introductory
      review of the QIF, with a strong emphasis on its applications. In particular, a
      recently developed SAS MACRO QIF is illustrated in this paper to obtain numerical
      results.

PMID- 19757487
TI  - Liver-restricted expression of the canine factor VIII gene facilitates prevention
      of inhibitor formation in factor VIII-deficient mice.
AB  - BACKGROUND: Gene therapy for hemophilia A with adeno-associated virus (AAV)
      vectors involves difficulties in the efficient expression of factor VIII (FVIII)
      and in antibody formation against transgene-derived FVIII. METHODS: AAV8 vectors
      carrying the canine B domain deleted FVIII (cFVIII) gene under the control of the
      ubiquitous beta-actin promoter, the liver-specific human alpha1 anti-trypsin
      promoter (HAAT) and the liver-specific hepatic control region (HCR)
      enhancer/human alpha1 anti-trypsin promoter complex (HCRHAAT) were used for the
      expression of cFVIII in FVIII deficient (fviii(-/-)) mice. RESULTS: Addition of
      the hepatic control region enhancer element to the HAAT promoter successfully
      augmented HAAT promoter activity without loss of liver-specificity in vivo. Using
      this enhancer/promoter complex, a high cFVIII transgene expression was achieved,
      resulting in increased blood cFVIII activities to more than 100% of the normal
      canine FVIII levels in fviii(-/-) mice at a 1 : 10 lower dose of the AAV8 vector
      carrying the cFVIII gene driven by the HAAT promoter. Under short-term
      immunosuppression, neutralizing antibodies against cFVIII developed in only one
      out of six mice when the HAAT promoter was used for cFVIII expression, whereas
      all the mice developed neutralizing antibodies against cFVIII when the beta-actin
      promoter was used for cFVIII expression. No neutralizing antibodies against
      cFVIII developed in fviii(-/-) mice that received the AAV8 vector carrying the
      cFVIII gene driven by the HCRHAAT enhancer/promoter complex without
      immunosuppression. CONCLUSIONS: These data suggest that AAV8 vector-mediated
      liver-restricted cFVIII gene expression is sufficient for immune hypo
      responsiveness to transgene-derived cFVIII in fviii(-/-) mice.

PMID- 19757488
TI  - A lentiviral vector-based adenovirus fiber-pseudotyping approach for expedited
      functional assessment of candidate retargeted fibers.
AB  - BACKGROUND: Many studies aimed at retargeting adenovirus (Ad) rationally focus on
      genetic modification of fiber, which is the primary receptor-binding protein of
      Ad. Retargeted fibers ultimately require functional validation in the viral
      context. METHODS: Lentiviral vectors (LV) were used to express fiber variants in
      cells. Infections with a fiber gene-deleted Ad vector yielded fiber-pseudotyped
      viruses. An enzyme-linked immunosorbent assay and slot blot-based assays probed
      target binding-ability of retargeted fibers. Differential treatments with an
      alkylating agent prior to western blot analysis allowed for examination of intra-
      and extracellular redox states of fibers. RESULTS: In the present study, LV-based
      fiber-pseudotyping of Ad is presented as an accelerated means to test new fibers.
      LV-mediated gene transfer yielded stable and uniform populations of fiber variant
      expressing cells. These populations were found to effectively support fiber
      pseudotyping of Ad. As a secondary objective of the study, we functionally
      assessed a chimeric fiber harboring a tumor antigen-directed single-chain
      antibody fragment (scFv). This fiber was shown to trimerize and achieve a degree
      of binding to its antigenic target. However, its capsid incorporation ability was
      impaired and, moreover, it was unable to confer a detectable level of target
      binding upon Ad. Importantly, subsequent analyses of this fiber revealed the
      improper folding of its scFv constituent. CONCLUSIONS: LV-based fiber
      pseudotyping was established as a convenient method for testing modified fibers
      for functionality within Ad particles. Furthermore, a new chimeric fiber was
      found to be inadequate for Ad retargeting. The folding difficulties encountered
      for this particular fiber might be generally inherent to the use (i.e. for
      genetic Ad capsid incorporation) of complex, disulfide bridge-containing natural
      ligands.

PMID- 19757489
TI  - PPARalpha and PPARgamma are co-expressed, functional and show positive
      interactions in the rat urinary bladder urothelium.
AB  - Some dual-acting PPARalpha + gamma agonists cause cancer in the rat urinary
      bladder, in some cases overrepresented in males, by a mechanism suggested to
      involve chronic stimulation of PPARalpha and PPARgamma, i.e. exaggerated
      pharmacology. By western blotting, we found that the rat urinary bladder
      urothelium expressed PPARalpha at higher levels than the liver and heart, and
      comparable to kidney. Urothelial expression of PPARgamma was above that of fat,
      heart, skeletal muscle and kidney. Male rats exhibited a higher
      PPARalpha/PPARgamma expression balance in the bladder urothelium than did female
      rats. Rats were treated by gastric gavage with rosiglitazone (PPARgamma agonist),
      fenofibrate (PPARalpha agonist) or a combination of rosiglitazone and fenofibrate
      for 7 days. In the urothelium, the transcription factor Egr-1 was induced to
      significantly higher levels in rats co-administered rosiglitazone and fenofibrate
      than in rats administered either rosiglitazone or fenofibrate alone. Egr-1 was
      also induced in the heart and liver of rats treated with fenofibrate, but a
      positive interaction between rosiglitazone and fenofibrate with regards to Egr-1
      induction was only seen in the urothelium. Thus, in the rat urinary bladder
      urothelium, PPARalpha and PPARgamma were expressed at high levels, were
      functional and exhibited positive interactions. Interestingly, fenofibrate
      induced the peroxisome membrane protein PMP70 not only in liver, but also in the
      bladder urothelium, opening the possibility that oxidative stress may contribute
      to rat urothelial carcinogenesis by dual-acting PPARalpha + gamma agonists.

PMID- 19757490
TI  - Physiological condition status and muscle-based biomarkers in rainbow trout
      (Oncorhynchus mykiss), after long-term exposure to carbamazepine.
AB  - Recently, residual pharmaceuticals are generally recognized as relevant sources
      of aquatic environmental pollutants. However, the toxicological effects of these
      contaminants have not been adequately researched. In this study, the chronic
      toxic effects of carbamazepine (CBZ), an anticonvulsant pharmaceutical commonly
      present in surface and ground water, on physiological condition status and muscle
      based biomarkers of rainbow trout were investigated. Fish were exposed at
      sublethal concentrations of CBZ (1.0 microg l(-1), 0.2 mg l(-1) and 2.0 mg l(-1))
      for 42 days. Compared with the control, there was a significant lower (P < 0.05)
      condition factor in fish exposed at the highest concentration of CBZ (2.0 mg l(
      1)), but the hepatosomatic indices in all groups were not significant changes. At
      lower CBZ concentration (1.0 microg l(-1), 0.2 mg l(-1)), the antioxidant enzyme
      activities were induced slightly, except catalase, while at the highest
      concentration (2.0 mg l(-1)) oxidative stress was apparent as reflected by the
      significant higher lipid peroxidation and protein carbonyls in the fish muscle,
      associated with a significant inhibition of antioxidant enzymes activities.
      Moreover, energy metabolic parameters (RNA-DNA ratio, Na(+)-K(+)-ATPase) were
      significantly inhibited in muscle of the fish exposed at the highest
      concentration (2.0 mg l(-1)), compared with the control. In short, CBZ-induced
      physiological and biochemical responses in fish were reflected in parameters
      measured in this study, which suggest that these biomarkers could be used as
      potential indicators for monitoring residual pharmaceuticals present in aquatic
      environment.

PMID- 19757492
TI  - Size, neurochemistry, and segmental distribution of sensory neurons innervating
      the rat tibia.
AB  - Retrograde labeling has been used to identify sensory neurons in the lumbar
      dorsal root ganglia (DRG) that innervate the rat tibial periosteum, medullary
      cavity, and trabecular bone. The size, neurochemical profile [isolectin B4 (IB4)
      binding, substance P (SP), calcitonin gene-related peptide (CGRP), and NF200
      immunoreactivity (-IR)], and segmental distribution of sensory neurons
      innervating each of these bony compartments are reported. After injections of
      fast blue into the periosteum, medullary cavity, and trabecular bone (epiphysis),
      retrogradely labeled neurons were observed throughout the ipsilateral (but not
      contralateral) lumbar DRG. They were predominantly small (<800 microm(2)) or
      medium-sized (800-1,800 microm(2)) neurons. CGRP-IR and SP-IR were found in 23%
      and 16% of the retrogradely labeled neurons, respectively. IB4 binding was
      observed in 20% and NF200-IR in 40% of the retrogradely labeled neurons. There
      were no significant differences in the percentage of neurons labeled with any one
      of the antisera following injections into each of the three bony compartments. To
      allow a direct comparison with sensory neurons innervating cutaneous tissues,
      injections of fast blue were also made into the skin overlying the tibia. The
      percentage of CGRP-IR neurons innervating bone was significantly lower than the
      percentage of CGRP-IR neurons innervating skin (ANOVA; P < 0.05). No other
      significant differences in the neurochemical profiles of neurons labeled from
      bone vs. skin were observed. The findings of the present study show that the
      periosteum, medullary cavity, and trabecular bone are all innervated by sensory
      neurons that have size and neurochemical profiles consistent with a role in
      nociception.

PMID- 19757493
TI  - Three-dimensional properties of GnRH neuroterminals in the median eminence of
      young and old rats.
AB  - The decapeptide gonadotropin-releasing hormone (GnRH), which regulates
      reproduction in all vertebrates, is stored in, and secreted from, large dense
      core secretory vesicles in nerve terminals in the median eminence. GnRH is
      released from these terminals with biological rhythms that are critical for the
      maintenance of normal reproduction. During reproductive aging in female rats,
      there is a loss of GnRH pulses and a diminution of the GnRH surge. However,
      information about the specific role of GnRH nerve terminals is lacking,
      particularly in the context of aging. We sought to gain novel ultrastructural
      information about GnRH neuroterminals by performing three-dimensional (3D)
      reconstructions of GnRH neuroterminals and their surrounding microenvironment in
      the median eminence of young (4-5 months) and old (22-24 months) ovariectomized
      Sprague-Dawley female rats. Median eminence tissues were freeze-plunge embedded
      and serial ultrathin sections were collected on slot grids for immunogold
      labeling of GnRH immunoreactivity. Sequential images were used to create 3D
      models of GnRH terminals. These reconstructions provided novel perspectives into
      the morphological properties of GnRH terminals and their neural and glial
      environment. We also noted that the cytoarchitectural features of the median
      eminence became disorganized with aging. Quantitative measures showed a
      significant decrease in the apposition between GnRH terminal membranes and glial
      cells. Our data suggest reproductive aging in rats is characterized by structural
      organizational changes to the GnRH terminal microenvironment in the median
      eminence.

PMID- 19757494
TI  - Distribution and neuronal expression of phosphatidylinositol phosphate kinase
      IIgamma in the mouse brain.
AB  - The role of cellular phosphatidylinositol 5-phosphate (PtdIns5P), as a signalling
      molecule or as a substrate for the production of small, compartmentalized pools
      of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P(2)], may be dependent on
      cell type and subcellular localization. PtdIns5P levels are primarily regulated
      by the PtdIns5P 4-kinases (type II PIP kinases or PIP4Ks), and we have
      investigated the expression and localization in the brain of the least-studied
      PIP4K isoform, PIP4Kgamma. In situ hybridization and immunohistochemistry, using
      antisense oligonucleotide probes and a PIP4Kgamma-specific antibody, revealed
      that this isoform has a restricted CNS expression profile. The use of antibodies
      to different cell markers showed that this expression is limited to neurons,
      particularly the cerebellar Purkinje cells, pyramidal cells of the hippocampus,
      large neuronal cell types in the cerebral cortex including pyramidal cells, and
      mitral cells in the olfactory bulb and is not expressed in cerebellar,
      hippocampal formation, or olfactory bulb granule cells. In neurons expressing
      this enzyme, PIP4Kgamma has a vesicular distribution and shows partial
      colocalization with markers of cellular compartments of the endomembrane
      trafficking pathway. The PIP4Kgamma isoform expression is established after day 7
      of postnatal development. Overall, our data suggest that PIP4Kgamma may have a
      role in neuron function, specifically in the regulation of vesicular transport,
      in specific regions of the developed brain.

PMID- 19757495
TI  - PICK1 expression in the Drosophila central nervous system primarily occurs in the
      neuroendocrine system.
AB  - The protein interacting with C kinase 1 (PICK1) protein was first identified as a
      novel binding partner for protein kinase C. PICK1 contains a membrane-binding BAR
      domain and a PDZ domain interacting with many synaptic proteins, including the
      alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor subunit
      GluR2 and the dopamine transporter. PICK1 is strongly implicated in GluR2
      trafficking and synaptic plasticity. In mammals, PICK1 has been characterized
      extensively in cell culture studies. To study PICK1 in an intact system, we
      characterized PICK1 expression immunohistochemically in the adult and larval
      Drosophila central nervous system. PICK1 was found in cell bodies in the
      subesophageal ganglion, the antennal lobe, the protocerebrum, and the
      neuroendocrine center pars intercerebralis. The cell types that express PICK1
      were identified using GAL4 enhancer trap lines. The PICK1-expressing cells form a
      subpopulation of neurons. PICK1 immunoreactivity was neither detected in
      glutamatergic nor in dopaminergic neurons. Also, we observed PICK1 expression in
      only a few GABAergic neurons, located in the antennal lobe. In contrast, we
      detected robust PICK1 immunolabeling of peptidergic neurons in the neuroendocrine
      system, which express the transcription factor DIMM and the amidating enzyme
      peptidylglycine-alpha-hydroxylating monooxygenase (PHM). The PICK1-positive cells
      include neurosecretory cells that produce the insulin-like peptide dILP2. PICK1
      expression in insulin-producing cells also occurs in mammals, as it was also
      observed in a rat insulinoma cell line derived from pancreatic beta-cells. At the
      subcellular level, PICK1 was found in the perinuclear zone but surprisingly not
      in synaptic domains. We conclude that PICK1 may serve an important role in the
      neuroendocrine system both in insects and vertebrates.

PMID- 19757496
TI  - Electrochemiluminescence detection of methamphetamine based on a Ru(bpy)3(2+)
      doped silica nanoparticles/Nafion composite film modified electrode.
AB  - An electrochemiluminescence (ECL) approach for methamphetamine determination was
      developed based on a glassy carbon electrode modified with a Ru(bpy)3 (2+)-doped
      silica nanoparticles/Nafion composite film. The monodispersed nanoparticles,
      which were about 50 nm in size, were synthesized using the water-in-oil
      microemulsion method. The ECL results revealed that Ru(bpy)3 (2+) doped in silica
      nanoparticles retained its original photo- and electrochemical properties. The
      ECL intensity was found to be proportional to methamphetamine concentration over
      the range from 1.0 * 10(-7) to 1.0 * 10(-5) mol L(-1), and the detection limit
      was found to be 2.6 * 10(-8) mol L(-1). The proposed ECL approach was used to
      analyze the methamphetamine content in drugs.

PMID- 19757497
TI  - Biocatalytic asymmetric amination of carbonyl functional groups - a synthetic
      biology approach to organic chemistry.
AB  - Transaminases catalyze amino transfer reactions from amino donors such as amino
      acids or amines to keto acids or ketones to give chiral amino acid or amines in
      optically pure form. alpha-Amino acid dehydrogenases catalyze the asymmetric
      reductive amination of alpha-keto acids using ammonia as amino donor to furnish L
      amino acids. The distinct features and synthetic application of these two enzymes
      are reviewed in an effort to illustrate their promising and challenging aspects
      in serving as approaches to the direct asymmetric synthesis of optically pure
      amines from the corresponding keto compounds, a formidable problem in organic
      chemistry.

PMID- 19757498
TI  - Eu3+ (orange/red) luminescence in LiXSO4Cl (X = Mg, Zn) halosulfate phosphor.
AB  - The wet chemical synthesis, X-ray diffraction and photoluminescence
      characteristics in alkaline halosulfate phosphors such as LiMgSO4Cl:Eu and
      LiZnSO4Cl:Eu are reported in this paper. The effect of Li ion on Eu3+
      luminescence (5D(0) --> 7F(2) electronic transition) and incorporation of Eu3+
      ion in lithium base alkaline halosulfate phosphor has been studied.

PMID- 19757499
TI  - Inheritance and stability of pyrethroid resistance in the cotton bollworm
      Helicoverpa armigera (Lepidoptera: Noctuidae) in Central Africa.
AB  - BACKGROUND: The cotton bollworm Helicoverpa armigera (Hubner) has developed
      esterase-mediated resistance to pyrethroids in Central Africa. To gain a better
      understanding of how quickly this resistance can evolve, its genetic basis and
      stability were examined in a field-derived strain of H. armigera (474-fold
      resistant to cypermethrin). RESULTS: Genetic crosses between susceptible,
      resistant and F(1) hybrids indicated that resistance was inherited as a dominant
      trait (D(LD) = 0.86) and conferred by a single autosomal gene. The dominance of
      resistance decreased as the cypermethrin dose increased, so that resistance was
      incompletely dominant (D(ML) = 0.73) at the highest dose tested. Resistance
      (DL(50)) of the F(1) hybrid progeny significantly decreased over five generations
      in the absence of pyrethroid exposure. CONCLUSION: Rapid selection of resistance
      alleles due to dominance supports the ability of H. armigera to develop
      resistance to pyrethroids in Central Africa. However, associated fitness costs
      provide useful information for managing the evolution of resistance.

PMID- 19757500
TI  - Evolutionary analysis of herbivorous insects in natural and agricultural
      environments.
AB  - Herbivorous insects offer a remarkable example of the biological diversity that
      formed the foundation for Darwin's theory of evolution by natural selection. The
      ability of insects to evolve resistance rapidly to insecticides and host-plant
      resistance present a continual challenge for pest management. This paper
      considers the manner in which genetic constraints, host-plant availability and
      trade-offs affect the evolution of herbivorous insects in natural and
      agricultural environments, and the extent to which lessons learned from studying
      natural systems may be applied to improve insect resistance management in
      agricultural systems. Studies on the genetic architecture of adaptation by
      herbivores to host plants and to insecticides are reviewed. The genetic basis of
      resistance is an important component of simulation models that predict the
      evolution of resistance. These models often assume monogenic resistance, but
      available data suggest that this assumption may be overly narrow and that
      modeling of resistance as oligogenic or polygenic may be more appropriate. As
      omics (e.g. genomics and proteomics) technologies become more accessible, a
      better understanding of the genetic basis of resistance will be possible. Trade
      offs often accompany adaptations by herbivores. Trade-offs arise when the benefit
      of a trait, such as the ability to feed on a novel host plant or to survive in
      the presence of an insecticide, is counterbalanced by fitness costs that decrease
      fitness in the absence of the selective agent. For resistance to insecticides,
      and resistance to insecticidal transgenic crops in particular, fitness costs may
      act as an evolutionary constraint and delay or prevent the evolution of
      resistance. An important observation is that certain ecological factors such as
      host plants and entomopathogens can magnify fitness costs, which is termed
      ecological negative cross-resistance. The application of omics technologies may
      allow for more efficient identification of factors that will impose ecological
      negative cross-resistance, thereby bolstering insect resistance management.

PMID- 19757501
TI  - Closeness in relationships as a mediator between sexual abuse in childhood or
      adolescence and psychopathological outcome in adulthood.
AB  - The risk of adverse psychological outcomes in adult victims of childhood and
      adolescent sexual abuse (CSA) has been documented; however, research on possible
      mediating variables is still required, namely with a clinical perspective. The
      attachment literature suggests that secure interpersonal relationships may
      represent such a variable. Twenty-eight women who had experienced episodes of
      CSA, and 16 control women, were interviewed using Bremner's Early Trauma
      Inventory and the DSM-IV Global Assessment of Functioning; they also responded to
      Collins' Relationship Scales Questionnaire, evaluating adult attachment
      representations in terms of Closeness, Dependence and Anxiety. Subjects with an
      experience of severe abuse reported significantly more interpersonal distance in
      relationships (low index of Closeness) than other subjects. The index of
      psychopathological functioning was correlated with both the severity of abuse and
      attachment (low index of Closeness). Regression analysis on the sample of abused
      women revealed that attachment predicted psychopathology when abuse was
      controlled for, whereas abuse did not predict psychopathology when attachment was
      controlled for. Therefore, preserving a capacity for closeness with attachment
      figures in adulthood appears to mediate the consequences of CSA on subsequent
      psychopathological outcome.

PMID- 19757502
TI  - Effect of reduced risk pesticides for use in greenhouse vegetable production on
      Bombus impatiens (Hymenoptera: Apidae).
AB  - BACKGROUND: Bumble bees [Bombus impatiens (Cresson)] are widely used for
      supplemental pollination of greenhouse vegetables and are at risk of pesticide
      exposure while foraging. The objective of this study was to determine the lethal
      and sub-lethal effects of four insecticides (imidacloprid, abamectin,
      metaflumizone and chlorantraniliprole) and three fungicides (myclobutanil,
      potassium bicarbonate and cyprodinil + fludioxonil) used or with potential for
      use in Ontario greenhouse vegetable production to B. impatiens. RESULTS:
      Imidacloprid, abamectin, and metaflumizone were harmful to worker bees following
      direct contact, while chlorantraniliprole and all fungicides tested were
      harmless. Worker bees fed imidacloprid-contaminated pollen had shortened life
      spans and were unable to produce brood. Worker bees consumed less pollen
      contaminated with abamectin. Metaflumizone, chlorantraniliprole and all
      fungicides tested caused no sub-lethal effects in bumble bee micro-colonies.
      CONCLUSION: We conclude that the new reduced risk insecticides metaflumizone and
      chlorantraniliprole and the fungicides myclobutanil, potassium bicarbonate and
      cyprodinil + fludioxonil are safe for greenhouse use in the presence of bumble
      bees. This information can be used preserve greenhouse pollination programs while
      maintaining acceptable pest management.

PMID- 19757503
TI  - Factors that affect risk of dementia.

PMID- 19757504
TI  - Hepatitis E in an HIV-infected patient.

PMID- 19757505
TI  - Congenital CMV- problems with diagnosis.

PMID- 19757506
TI  - PIC cystography: an effective test for the diagnosis of clinically significant
      occult reflux.

PMID- 19757507
TI  - An interview with Dr. Giuseppe Viglietto on his highly cited paper published in
      Cell Cycle.

PMID- 19757509
TI  - Obituary.

PMID- 19757508
TI  - [Management of patients with GERD. Clinical practice guideline. 2008 update.
      Clinical Practice Guideline Working Group on GERD].

PMID- 19757510
TI  - Five candidates compete for regional director of WHO EURO. Interview by Clare
      Kapp and Udani Samarasekera.

PMID- 19757511
TI  - Lead poisoning cases spark riots in China.

PMID- 19757512
TI  - The death of Ivan Ilyich and pain relief at the end of life.

PMID- 19757514
TI  - Comparison of two schemes of small bowel preparation  for capsule endoscopy with
      polyethylene glycol:  a prospective, randomized single-blind study.
AB  - OBJECTIVE: Small bowel preparation for capsule endoscopy remains controversial.
      This study was conducted to compare the efficacy of 2 and 4 l of polyethylene
      glycol. METHODS: One hundred and one patients (group A) received 2 l and 100
      (group B) received 4 l in a prospective, randomized single-blind trial. To
      objectively evaluate enteric preparation, a cleansing coefficient was calculated
      for each patient. RESULTS: The two groups were found comparable regarding age,
      sex, body mass index, and reason for referral. In 82 patients of group A and in
      76 of group B, examination of small bowel was completed (P =0.40). Gastric
      emptying time and small bowel transit time were found comparable in both groups.
      Cleansing coefficients, for small bowel as a whole or for proximal or distal
      separately, were similar among the two groups. However, the cleansing coefficient
      of the proximal bowel was significantly higher than that of the distal,
      independently of preparation (group A: P < 0.001, group B: P< 0.001). Small bowel
      preparation was related only with the age of the patients and gastric emptying
      time; the younger the patient or the shorter the gastric emptying time, the
      higher the cleansing coefficient. Pathological findings were found in 43 (42.6%)
      patients of group A and in 37 (37.0%) patients of group B (P =0.42). A final
      positive diagnosis was established in 33 (32.7%) patients of group A and in 29
      (29.0%) of group B (P = 0.57). CONCLUSION: The two schemes were equal regarding
      enteric cleansing and completion of the procedure. Therefore, 2 l seems to be an
      adequate preparation for capsule endoscopy.

PMID- 19757515
TI  - Proceedings of the 24th International Workshop on Surfactant Replacement.
      Workshop dedicated in memory of Bengt Robertson. Ljubljana, Slovenia June 4-6,
      2009.

PMID- 19757516
TI  - Proceedings of the First Symposium of the Reduced-Intensity Conditioning
      Subcommittee of the Acute Leukemia Working Party of the European Group for Blood
      and Marrow Transplantation (EBMT). Nantes, France. November 15, 2008.

PMID- 19757517
TI  - Training compensation or not?

PMID- 19757518
TI  - Single-payor systems.

PMID- 19757519
TI  - Ethical issues.

PMID- 19757521
TI  - Allergic manifestations in autoimmune pancreatitis.
AB  - OBJECTIVE: Autoimmune pancreatitis (AIP) is a peculiar type of pancreatitis of
      presumed autoimmune etiology. However, target antigens for AIP have not been
      detected. Furthermore, its preponderant occurrence in elderly men and the very
      dramatic response with no major residual deformity to oral steroid therapy within
      2 weeks suggest that the pathogenesis of AIP might not involve autoimmune
      mechanism. Recently, it was reported that the immune reaction closely involved in
      the pathogenesis of allergic disorders was upregulated in the affected tissues of
      AIP. This study aimed to examine the allergic manifestations in AIP patients.
      METHODS: This case series consisted of 45 AIP patients. Present and/or past
      histories of allergic diseases, clinical findings, and laboratory data were
      reviewed. RESULTS: Twenty patients (allergic-type AIP) had histories of allergic
      diseases, such as acute allergic rhinitis (n= 11), including rose and hay fever,
      atopic dermatitis (n= 5), bronchial asthma (n= 3), drug allergy (n= 2), and
      hypersensitivity pneumonitis (n= 1). Serum IgE levels were elevated in only 12
      allergic-type AIP patients, and they were significantly higher in allergic-type
      AIP patients than in AIP patients without allergic manifestations (P = 0.0001).
      The peripheral eosinophil count was significantly elevated in allergic-type AIP
      patients (P =0.048). With respect to initial symptoms, obstructive jaundice was
      less frequent in allergic-type AIP patients (P = 0.012), and abdominal pain was
      detected in only five patients with allergic-type AIP (P = 0.013). Allergic-type
      AIP occurred predominantly from September to February in 19 of 20 patients (P =
      0.001). CONCLUSION: Allergic manifestations were detected in about half of the
      AIP patients, and allergic mechanisms may be related to the occurrence of AIP in
      these patients.

PMID- 19757520
TI  - Stress questionnaires and stress biomarkers during pregnancy.
AB  - OBJECTIVE: Both self-reported indicators of stress and hormones such as cortisol
      and corticotrophin-releasing hormone (CRH) have been examined in relation to
      preterm birth. Although these hormones have been interpreted as biomarkers of
      stress, it is unclear whether psychosocial measures are empirically associated
      with biomarkers of stress in pregnant women. METHODS: We analyzed data from 1,587
      North Carolina pregnant women enrolled in the Pregnancy, Infection,and Nutrition
      study during 2000-2004 who provided at least one saliva sample for cortisol
      measurement or blood samples for CRH at 14-19 and 24-29 weeks' gestation.
      Cortisol measures were limited to those taken between 8 and 10 a.m. Perceived
      stress, state-trait anxiety, coping style, life events, social support, and
      pregnancy-specific anxiety were measured by questionnaires and interviews.
      Spearman correlations and multiple regressions were used to describe the
      relationship among the measures of stress. RESULTS: No correlations larger than r
      = 0.15 were seen between reported psychosocial measures and cortisol or CRH.
      Women with demographic characteristics associated with poor pregnancy outcomes
      (unmarried, African-American, young, low pre-pregnancy body mass index) reported
      higher levels of stress but did not consistently have higher levels of stress
      hormones. Pre-eclampsia was associated with higher CRH, but not with higher
      cortisol. CONCLUSIONS: The relationship between measurements of reported stress
      and biomarkers is not straightforward in large epidemiological studies of
      pregnancy.

PMID- 19757523
TI  - Proceedings of the Italian Group of Scoliosis Study Congress. 2008.

PMID- 19757522
TI  - Infliximab in clinical routine: experience with Crohn's disease and biomarkers of
      inflammation over 5 years.
AB  - INTRODUCTION: Infliximab was launched for the treatment of Crohn's disease (CD)
      in 1999. We set up a follow-up protocol to meticulously study disease development
      with repeated infusions of infliximab. AIM: To follow the effects of infliximab
      treatment on disease activity, blood chemistry, quality of life, plasma nitrite,
      and titers of Saccharomyces cerevisiae antibodies (ASCA). METHODS: During 1999
      2008, CD patients were monitored for disease activity by Harvey-Bradshaw index,
      blood chemistry with hemoglobin, albumin, C-reactive protein, platelet count,
      leukocyte count and creatinine, quality of life by the Short Health Scale, and
      plasma nitrite. During the first year of treatment, follow-up was done repeatedly
      before and 1 week after each infusion and thereafter every year before the last
      infusion for 5 years. ASCA was analyzed by flow cytometry with fluorescein
      isothiocyanate-labelled antibodies. RESULTS: A total of 1061 infusions were given
      to 103 patients; 92 responders and 11 nonresponders. Responders were further
      monitored and Harvey-Bradshaw index decreased with infusions during the first
      year of treatment (P < 0.0001), whereas hemoglobin (P < 0.01) and albumin (P
      <0.001) increased, C-reactive protein (P < 0.01) decreased, platelets (P <0.001)
      increased, and leukocytes (P< 0.01) decreased. Creatinine was not affected. Short
      Health Scale (questions analyzed separately) decreased (P < 0.0001), and nitrite
      (P < 0.001) increased. During the next 4 years the improved values remained
      stable. Adverse effects were noted among 32% of the patients; local circulatory
      reactions being most common. No correlation between ASCA titers and inflammatory
      activity or infliximab treatment was found. CONCLUSION: Infliximab treatment is
      highly effective in responders and maintains symptomatic improvement and low
      inflammatory activity over years in CD patients.

PMID- 19757524
TI  - Health tips.  West Nile virus.

PMID- 19757526
TI  - Groin rashes.  Find some relief.

PMID- 19757525
TI  - Beyond PSA:  will future biomarker tests be better?

PMID- 19757527
TI  - Fiber in food.  From good to great.

PMID- 19757528
TI  - I recently had a colonoscopy test that showed no polyps. But my doctor told me
      that I need to have another colonoscopy in the next couple of years because my
      colon preparation hadn't been thorough enough. Is this common? And what can I do
      prevent this from happening the next time?

PMID- 19757529
TI  - Walking: your steps to health.

PMID- 19757531
TI  - Age and performance.

PMID- 19757530
TI  - Arsenic and prostate cancer.

PMID- 19757532
TI  - On call. My husband subscribes to "Harvard Men's Health Watch," but I read it and
      like it as much as he does. Since he listens to your advice, I hope you can
      resolve a problem that worries me. My husband refuses to throw out pills that are
      past expiration dates. I never keep foods longer than I should, so I hope you'll
      convince him to clean out the medicine closet the way I take care of the fridge
      and pantry.

PMID- 19757533
TI  - On call. I don't have allergies, but my eyes often burn and itch. My vision is
      fine, but my eyes are sometimes bloodshot, and I come down with two or three
      sties a year. I don't want to bother my doctor with such a minor problem, but I
      wonder if you can help.

PMID- 19757534
TI  - [Humanism and freedom of choice: what do we want to buy--and what are we selling?
      ].

PMID- 19757535
TI  - Moral transgression and illness in the Early Modern North.
AB  - This article seeks to understand how people in the early modern age interpreted
      the nature of illness and the role that morality played in these interpretations.
      From this point of view illnesses were not only psycho-physical states or
      subjects for medical diagnosis but they were also subjects for narratives or
      stories through which people tried to understand what had caused their illness,
      and why it was happening to them. Illnesses were understood as strictly connected
      with the patient's character and were regarded as possible consequences of his
      personality. On the other hand, the interpretations also emphasised the
      ambivalence of a healer. Personal experiences and an understanding of one's life
      situation intertwined in these stories.

PMID- 19757536
TI  - Moral transgression, disease and holistic health in the Livingstonia Mission in
      late nineteenth and early twentieth-century Malawi.
AB  - This article examines ideas of morality and health, and connections between moral
      transgression and disease in both Scottish missionary and Central African thought
      in the context of the Livingstonia Mission of the Presbyterian Free Church of
      Scotland in Malawi during the late nineteenth and early twentieth centuries. By
      concentrating on debates, conflicts and co-operation between missionaries and
      Africans over the key issues of beer drinking and sexual morality, this article
      explores the emergence of a new "moral hygiene" among African Christian
      communities in Northern Malawi.

PMID- 19757537
TI  - The provision and reporting of community benefits by hospitals: lessons from
      Maryland.
AB  - (1) Most Maryland hospitals experienced a difficult learning curve in 2004 when
      they were required to begin filing annual reports on community benefit
      expenditures, but hospital leaders now generally see the reporting requirements
      to have been beneficial for hospitals. (2) Charity care and health professional
      education each account for about one-third of community benefit expenditures in
      Maryland hospitals, and mission-related services around 20 percent. (3) Community
      benefit accounts for more that [sic] 7.2 percent of hospitals' expenditures on
      average, with the range from less than two percent to more than 14 percent.
      Charity care averages 2.1 percent of expenditures, with the range from less than
      1 percent to more than 6 percent of expenses.

PMID- 19757538
TI  - Stimulus bill implementation: expanding meaningful use of health IT.
AB  - The American Recovery and Reinvestment Act authorizes an estimated $38 billion in
      incentives and supports for health information technology (IT) from 2009 to 2019.
      After years of sluggish HIT adoption, this crisis-driven investment of public
      funds creates a unique opportunity for rapid diffusion of a technology that is
      widely expected to improve care, save money, and facilitate transformation of the
      troubled U.S. health system. Achieving maximal effect from the stimulus funds is
      nevertheless a difficult challenge. The Recovery Act strengthens the federal
      government's leadership role in promoting HIT. But successful adoption and
      utilization across the health system will also require development of a
      supportive infrastructure and broad-based efforts by providers, vendors, state
      based agencies, and other health system stakeholders. Optimal use of IT for
      health care may require extensive reengineering of medical practice and of
      existing systems of payment. The future course of HIT adoption will also be
      subject to the effects of any health care reform legislation and of technological
      innovation in the fast-changing world of electronic communications

PMID- 19757539
TI  - [Ibuprofen induced agranulocytosis?].

PMID- 19757540
TI  - [Lymphocytic colitis probably due to etifoxine. A case with relapse after
      reintroduction].

PMID- 19757541
TI  - Re: Effects of maxillary protraction and fixed appliance therapy on the
      pharyngeal airway.

PMID- 19757542
TI  - Guest editors' introduction to the special section on probabilistic graphical
      models.

PMID- 19757543
TI  - Updates on dose conversion ratio between two botulinum toxin A preparations when
      injected in the sweat glands.

PMID- 19757544
TI  - Leadership committed to safety.

PMID- 19757545
TI  - Lameness in dairy cattle: A debilitating disease or a disease of debilitated
      cattle? A cross-sectional study of lameness prevalence and thickness of the
      digital cushion.
AB  - Lameness is the most significant challenge for the dairy industry to overcome,
      given its obvious disruption of animal welfare and severe economic losses. Sole
      ulcers and white line abscesses are ubiquitous chronic diseases with the highest
      associated economic losses among all foot lesions. Their underlying causes are
      still not fully understood. An observational cross-sectional study was carried
      out to investigate the association between claw horn lesions and the thickness of
      the digital cushion.The thickness of the digital cushion was evaluated by
      ultrasonographic examination of the sole at the typical ulcer site. A total of
      501 lactating Holstein dairy cows were enrolled in the study. The prevalence of
      sole ulcers was 4.2 and 27.8% for parity 1 and parity >1, respectively.The
      prevalence of white line disease was 1.0 and 6.5% for parity 1 and >1,
      respectively. The prevalence of lameness (visual locomotion score > or = 3) was
      19.8 and 48.2% for parity 1 and >1, respectively. The prevalence of sole ulcers
      and white line diseases was significantly associated with thickness of the
      digital cushion; cows in the upper quartile of digital cushion thickness had an
      adjusted prevalence of lameness 15 percentage points lower than the lower
      quartile. Body condition scores were positively associated with digital cushion
      thickness.The mean gray value of the sonographic image of the digital cushion had
      a negative linear association with digital cushion thickness (R2 = 0.14),
      indicating that the composition of the digital cushion may have changed with its
      thickness. Furthermore, digital cushion thickness decreased steadily from the
      first month of lactation and reached a nadir 120 d after parturition.These
      results support the concept that sole ulcers and white line abscesses are related
      to contusions within the claw horn capsule and such contusions are a consequence
      of the lesser capacity of the digital cushion to dampen the pressure exerted by
      the third phalanx on the soft tissue beneath.

PMID- 19757546
TI  - Teen driver tune-up: a move is underway to impose national standards on teen
      drivers.

PMID- 19757547
TI  - Improving the odds: dozens of states aim to help minorities and low-income
      residents receive better medical care and live healthier lives.

PMID- 19757548
TI  - Population pharmacokinetics and dosing recommendations for cisplatin during
      intraperitoneal peroperative administration.

PMID- 19757549
TI  - Tactics and economics of wildlife oral rabies vaccination, Canada and the United
      States.
AB  - Progressive elimination of rabies in wildlife has been a general strategy in
      Canada and the United States; common campaign tactics are trap-vaccinate-release
      (TVR), point infection control (PIC), and oral rabies vaccination (ORV). TVR and
      PIC are labor intensive and the most expensive tactics per unit area
      (approximately $616/km(2) [in 2008 Can$, converted from the reported $450/km(2)
      in 1991 Can$] and approximately $612/km(2) [$500/km(2) in 1999 Can$],
      respectively), but these tactics have proven crucial to elimination of raccoon
      rabies in Canada and to maintenance of ORV zones for preventing the spread of
      raccoon rabies in the United States. Economic assessments have shown that during
      rabies epizootics, costs of human postexposure prophylaxis, pet vaccination,
      public health, and animal control spike. Modeling studies, involving diverse
      assumptions, have shown that ORV programs can be cost-efficient and yield
      benefit:cost ratios >1.0.

PMID- 19757550
TI  - Spread of Cryptococcus gattii into Pacific Northwest region of the United States.
AB  - Cryptococcus gattii has emerged as a human and animal pathogen in the Pacific
      Northwest. First recognized on Vancouver Island, British Columbia, Canada, it now
      involves mainland British Columbia, and Washington and Oregon in the United
      States. In Canada, the incidence of disease has been one of the highest
      worldwide. In the United States, lack of cryptococcal species identification and
      case surveillance limit our knowledge of C. gattii epidemiology. Infections in
      the Pacific Northwest are caused by multiple genotypes, but the major strain is
      genetically novel and may have emerged recently in association with unique mating
      or environmental changes. C. gattii disease affects immunocompromised and
      immunocompetent persons, causing substantial illness and death. Successful
      management requires an aggressive medical and surgical approach and consideration
      of potentially variable antifungal drug susceptibilities. We summarize the study
      results of a group of investigators and review current knowledge with the goal of
      increasing awareness and highlighting areas where further knowledge is required.

PMID- 19757551
TI  - Expert consensus on treatment strategies in non- ST-segment elevation acute
      coronary syndromes in patients undergoing percutaneous coronary intervention--an
      evidence-based review of clinical trial results and treatment guidelines from an
      emergency medicine perspective: report on a roundtable discussion.

PMID- 19757552
TI  - Out of options: why so many workers in small businesses lack affordable health
      insurance, and how health care reform can help. Findings from the Commonwealth
      Fund Biennial Health Insurance Survey, 2007.
AB  - Although employer-sponsored health insurance forms the backbone of the health
      insurance system in the United States, small businesses are finding it
      increasingly difficult to provide their workers with comprehensive coverage. In
      2007, only 25 percent of employees in small businesses had coverage through their
      own employers, compared with 74 percent of workers in large firms. Because there
      are few sources of affordable coverage outside the employer-based system,
      millions of employees in small businesses are uninsured or have inadequate health
      insurance. In 2007, 52 percent of workers in small businesses were uninsured or
      underinsured during the year, compared with half as many employees in large
      businesses. Congressional bills to reform the health system include provisions
      specifically aimed at helping small businesses and their employees gain access to
      affordable, comprehensive coverage.

PMID- 19757553
TI  - Efficacy of imidacloprid on dogs and cats with natural infestations of fleas,
      with special emphasis on flea hypersensitivity.
AB  - In this study the efficacy of a 10% weight per volume solution of imidacloprid-
      registered as a flea control agent with the trademark Advantage topical solution-
      was assessed in Italy under field conditions in a total of 3272 dogs and cats.
      During the 4-week trial the number of fleas on each animal was assessed and
      lesions of flea allergy dermatitis (FAD; i.e., miliary or maculopapular
      dermatitis, hyperpigmentation, and crusty thickenings of the skin), alopecia, and
      pruritus were evaluated. Imidacloprid had a notable adulticidal effect and
      residual activity that controlled fleas and prevented reinfestation of treated
      animals for at least 4 weeks. In addition, a significant decrease of the clinical
      signs was documented regardless of each animal's breed, sex, body size, haircoat
      length, and living conditions. Some of the dogs were washed or shampooed after
      treatment without showing statistical differences in efficacy. This study
      demonstrates that a single treatment with imidacloprid is able to effectively
      control flea infestations in dogs and cats for at least 28 days and significantly
      contributes to the improvement or disappearance of clinical signs of FAD.

PMID- 19757554
TI  - Radiographic diagnosis of feline heartworm disease and correlation to other
      clinical criteria: results of a multicenter clinical case study.
AB  - Two-hundred fifteen cats with clinical signs consistent with feline heartworm
      disease (FHD) were entered into this clinical case study. In addition to physical
      examination, CBC, and heartworm antibody (Ab) and antigen (Ag) tests, thoracic
      radiographs were taken of 212 cats at initial examination. For cats that had a
      positive Ab or Ag test, or radiographic changes that could be associated with
      FHD, follow-up radiographs were taken at approximately 60 to 90 days after
      initial examination whenever possible. Each radiographic examination included VD,
      DV, and left lateral views, and each was read by the same board-certified
      radiologist who was blinded to heartworm serological results until after
      radiographic evaluation was completed. Criteria evaluated included heart size and
      shape, pulmonary artery enlargement, pulmonary parenchymal involvement,
      hyperinflation of lungs, tenting of the diaphragm, and pleural fluid
      accumulation. Summary interpretations and heartworm score were recorded. The
      heartworm score reflected the degree of suspicion of FHD based on radiographic
      signs: no radiographic signs of FHD; bronchointerstitial lung pattern only
      (consistent with but not specific for FHD); or pulmonary artery enlargement (with
      or without pulmonary or cardiac changes) mildly, moderately, or strongly
      indicative of FHD. Of 212 cats for which radiographs were taken at the initial
      examination, 38 (18%) had enlarged caudal lobar arteries indicative of FHD and 90
      (42%) had bronchointerstitial pulmonary disease consistent with heartworms and/or
      enlarged caudal lobar arteries. Radiographic changes consistent with or
      indicative of FHD were evident in 9/22 cats (41%) presenting with
      gastrointestinal signs, 39/78 cats (50%) presenting with respiratory signs, and
      41/80 cats (51%) presenting with both respiratory and gastrointestinal signs.
      Some cats presenting with only gastrointestinal signs had thoracic radiographic
      changes suggestive of FHD. Eleven cats tested DiroCHEK Ag positive, and
      radiographs were taken of 10. Of the 10 cats, 5 had radiographic changes
      indicative of FHD; one had changes consistent with FHD; and 4 cats showed no
      radiographic signs of FHD. Follow-up radiographs were taken of 6 of these 11
      cats: 1/6 worsened in radiographic score, 3/6 improved in radiographic score, and
      2/6 still demonstrated no radiographic signs of heartworm. Ninety-two cats tested
      Ab positive at initial examination, and radiographs were available for 91 of
      these cats. In 22/91 (24%), enlarged caudal lobar arteries indicated FHD. In
      39/91 cats (43%) cats, radiographic signs consistent with or indicative of FHD
      were seen. Of the 38 cats that had radiographic signs indicative of FHD, 22 (58%)
      were Ab positive on one or both tests. Seven (32%) had positive DiroCHEK Ag tests
      at initial or recheck examination. At recheck examinations, 2 cats that initially
      had radiographic signs indicative of FHD converted from DiroCHEK Ag negative to
      positive, confirming their infection with at least 1 sexually mature female
      heartworm. While many affected cats show pulmonary arterial enlargement and/or a
      bronchointerstitial pattern typical of FHD, some cats with serologic evidence of
      heartworms do not demonstrate any thoracic radiographic changes. Conversely, some
      cats show radiographic signs suggesting heartworm disease when concurrent
      serology is negative. These discrepancies may be caused by time between infection
      and examination, by differences in individual cats' immune response to the
      presence of larval or adult stages of heartworm, or by aberrant migrations.

PMID- 19757555
TI  - Prevalence of feline heartworm infections among cats with respiratory and
      gastrointestinal signs: results of a multicenter study.
AB  - Although heartworm infection in cats was first described in 1921, the diagnosis
      of the infection remains elusive in many cases. This is due to nonspecific
      clinical signs of feline heartworm disease, typically low worm burdens, unique
      pathophysiology in the cat, and the limitations of currently available heartworm
      tests. Consequently, knowledge about this disease is still limited. An objective
      of this study was to survey the occurrence and clinical presentation of feline
      heartworm infection among cats presenting with clinical signs consistent with
      heartworm disease. Two-hundred fifteen cases were submitted from 15 private
      practices in Florida, South Carolina, Tennessee, and Texas. Cats entered in the
      study were at least 6 months of age and presented with one or more of the
      following clinical signs: respiratory signs, including tachypnea, dyspnea, or
      coughing; gastrointestinal signs, including a pattern of intermittent vomiting
      unrelated to eating; or sudden death of uncertain etiology, particularly
      associated with respiratory distress prior to death. Data collected included:
      history and indoor/ outdoor lifestyle; physical examination findings; thoracic
      radiography evaluations; Knott or DIFIL test results, DiroCHEK antigen test
      results, and antibody test results (Animal Diagnostics, Inc. and Heska
      Corporation); and CBC results. Recheck examinations were scheduled for any cat
      with positive heartworm serological test results and for cats with radiographic
      signs consistent with or suggestive of feline heartworm disease. Data from 215
      cases were collected and analyzed: 94/215 (44%) tested antibody positive for one
      or both antibody tests that were performed; 18/94 (19%) of the antibody-positive
      cats were reported as living 100% indoors by their owners; (12%) of the antibody
      positive cats spent less than or equal to 10% of their time outdoors. Eleven of
      215 cats (5%) were DiroCHEK antigen positive on initial examination. One cat was
      both DiroCHEK and microfilariae positive, but negative for both antibody tests.
      Radiographs were obtained for 10 of these cats and 6/10 had radiographic signs
      consistent with or suggestive of feline heartworm infection. At necropsy,
      heartworms were found in one other cat from which blood was not obtained.
      Additionally, two cats that had positive radiographic signs of heartworm
      infection converted from antigen-negative to antigen-positive status at recheck
      examination for a total of 13/215 (6%) DiroCHEK antigen-positive cats. One case
      that was submitted after acute death was DiroCHEK antigen positive, but
      interestingly, had relatively low antibody levels for both antibody tests.
      Initial radiographs were available on 212 of the 215 cases. In 90/212 (42%)
      cases, initial thoracic radiographs showed signs consistent with or suggestive of
      heartworm disease. Follow-up radiographs showed varying progression with
      radiographic signs worsening, improving, or staying the same on individual cats.
      Feline heartworm disease should be among the primary differential diagnoses in
      cats with respiratory disease, vomiting, or acute death. Radiography, antibody
      testing, and antigen testing are all useful tools to aid in making the diagnosis.
      A confirmed diagnosis may require doing multiple tests and clinical reevaluation.
      Cats classified by their owners as indoor only cats were found to be heartworm
      infected, thus lifestyle of the cat cannot rule out the disease. Actual antibody
      levels (high or low) may not correspond to severity of disease.

PMID- 19757556
TI  - Efficacy of a nonadjuvanted, outer surface protein A, recombinant vaccine in dogs
      after challenge by ticks naturally infected with Borrelia burgdorferi.
AB  - In a blinded, controlled study, thirty purpose-bred, Borrelia burgdorferi
      negative, mixed-breed dogs 10 to 12 weeks of age were randomly divided into three
      groups of ten animals each for the purpose of evaluating a recombinant
      nonadjuvanted B. burgdorferi OspA vaccine (Recombitek Lyme [Merial Limited]) for
      efficacy and safety. Two groups received two doses of two different lots ofa
      nonadjuvanted, OspA, recombinant vaccine; the third group served as nonvaccinated
      controls. All dogs were challenged 3 weeks after the second vaccination with
      blacklegged deer ticks (Ixodes scapularis) harvested from a B. burgdorferi
      endemic area in Rhode Island. Clinical signs, antibody titers by ELISA, Western
      blot assays, and isolation and polymerase chain reaction analyses of spirochetes
      from biopsy specimens were used to evaluate vaccine efficacy. Direct fluorescent
      antibody assay was used to evaluate the infection rate in the challenge ticks and
      in naive ticks allowed to feed on study dogs after the dogs were infected
      (xenodiagnosis). Vaccinates responded with high levels of antibodies (determined
      by ELISA and measured by optical density [OD]), which did not rise after
      challenge. Vaccinates demonstrated no clinical signs, negative isolation of
      spirochetes on biopsy, only an OspA antibody pattern on Western blot assay, and
      negative isolation of spirochetes on biopsy, confirming that the vaccine blocked
      infection with B. burgdorferi in all vaccinated dogs (20/20). Control dogs
      demonstrated clinical signs (2/10), antibodies characteristic of infection with
      B. burgdoferi (10/10), isolation of spirochetes (10/10), and polymerase chain
      reaction (PCR) detection of spirochetes (9/10). The recombinant, nonadjuvanted B.
      burgdoferi vaccine protected 100% of vaccinates against infection after a severe
      challenge that infected 100% of control dogs. The OspA vaccine proved to be
      highly safe and effective in this study.

PMID- 19757557
TI  - Hematologic, hemostatic, and biochemical effects in cats receiving an oral
      chondroprotective agent for 30 days.
AB  - The objective of this study was to evaluate the effects of a chondroprotective
      agent on hematologic, hemostatic, and biochemical variables in clinically normal
      cats when administered at twice the recommended levels for 30 days. Fifteen
      clinically normal female domestic shorthaired cats were used. Twelve cats were
      given a chondroprotective agent orally, twice daily for 30 days. Three cats
      served as environmental controls and did not receive any treatment. The
      Wilcoxon's rank sum with a Bonferroni correction was used to evaluate the data
      statistically. Hematologic, hemostatic, and biochemical variables were assessed
      before treatment and on days 3, 14, and 30 of treatment. All cats remained
      healthy and showed no adverse reactions to treatment. No clinically and
      statistically significant shift outside a standard reference range was noted for
      any parameter. Hematocrit and red blood cell concentrations were decreased from
      pretreatment concentrations during days 3, 14, and 30 of treatment; however,
      these values were within a standard reference range at all time points. No
      significant changes were noted in platelet count, prothrombin time, or activated
      partial thromboplastin time. There were significant decreases in platelet
      aggregation response to high and low concentrations of collagen on day 3 and to
      the high concentration of collagen on days 14 and 30 compared with pretreatment
      values, but these values were not different from those of untreated cats. There
      was an increased time to response with the high concentration but not the low
      concentration of collagen on days 3, 14, and 30. Some parameters, such as
      potassium, anion gap, alkaline phosphatase, and bicarbonate, showed changes from
      pretreatment values at some but not all days of treatment. However, median
      concentrations remained within normal reference ranges, suggesting that these
      minor shifts were not indicative of clinical significance. Oral chondroprotective
      agents are widely prescribed in veterinary medicine for the treatment of
      degenerative joint disease. Safety studies have been performed in dogs; however,
      to date little is known about the safety of their use in cats. In this study,
      administration of this chondroprotective agent did not result in any clinically
      important change in hematologic, biochemical, and hemostatic variables when
      administered to healthy adult cats for 30 days at twice the recommended dosage.

PMID- 19757558
TI  - Effects of avilamycin on performance of broiler chickens.
AB  - The benefits of feeding avilamycin (Surmax/Maxus, Elanco Animal Health) to
      broiler chickens were demonstrated in a floor pen study (two trials) in which
      avilamycin was fed at 10 ppm in a 45-day growout. Final live weight of broilers
      fed avilamycin was significantly (P < or = .01) heavier (90 g) than that of
      control broilers fed for an equal number of days. Feed conversion was numerically
      but not significantly improved by avilamycin. Dressing percentage (hot
      eviscerated carcass weight/live weight) of broilers fed avilamycin was
      significantly improved (P < or = .01) relative to that of control broilers fed
      for an equal number of days.

PMID- 19757559
TI  - Cerebrospinal fluid and blood concentrations of toltrazuril 5% suspension in the
      horse after oral dosing.
AB  - Toltrazuril 5% suspension (Baycox, Bayer Canada, Ontario, Canada) was
      administered to six adult horses followed by blood collection and assay to
      determine the concentration of toltrazuril and its principal metabolites,
      toltrazuril sulfone and toltrazuril sulfoxide. From this data, the maximum
      concentration (C(max)), elimination half-life (T 1/2), and mean residence times
      of the plasma were determined from standard pharmacokinetic formulas. After a
      single oral dose of 10 mg/kg body weight a rapid absorption was found, with a
      mean peak serum concentration of 11.17 mg/L at 18 hours. Elimination was
      prolonged, with a mean T 1/2 for elimination of 61.4 hours. In addition,
      toltrazuril was administered to nine horses, and blood serum and cerebrospinal
      fluid (CSF) concentrations of toltrazuril and its principal metabolites were
      determined. Horses were randomly assigned to one of three treatment groups and
      received either 2.5 mg/kg body weight (Group A), 5.0 mg/kg body weight (Group B),
      or 7.5 mg/kg body weight (Group C) orally, once daily, for 10 days. Jugular
      venous blood was collected routinely on treatment days 2, 6, and 10, and CSF was
      collected on treatment day 10. Assay of toltrazuril and its metabolites revealed
      a dose-dependent effect within both the blood and CSF compartments. Mean
      concentrations within the CSF after 10 days of treatment were 0.146 mg/L in Group
      A, 0.190 mg/L in Group B, and 0.386 mg/L in Group C. Toltrazuril sulfone was the
      primary metabolite after 10 days of treatment, with concentrations that ranged
      from 39% to 116% of the parent drug in individual animals. Toltrazuril sulfone
      was also the predominant metabolite in the serum at treatment day 10; however, it
      did not always exceed the concentration of toltrazuril sulfoxide in the serum on
      treatment day 2. In the serum, drug concentrations at treatment day 2 were
      variable in the low-dose group (Group A), ranging from 4.0 to 11.61 mg/L; less
      variable in the high-dose group (Group C), ranging from 9.9 to 10.46 mg/L; and
      intermediate in Group B. This study confirms that toltrazuril is absorbed in the
      horse after oral administration and reaches effective in vitro concentrations
      within the CSF of the horse after once-daily dosing of 5 or 7.5 mg/kg. Although
      these data suggest that toltrazuril may have clinical value in the treatment of
      equine protozoal myeloencephalitis, clinical efficacy remains to be confirmed
      using appropriate methods. Effective in vitro concentrations are known; however,
      therapeutic concentrations in vivo have not been established. Further research in
      this area is needed to determine various drug values in the CSF (e.g., half-life,
      C(max), time to reach steady state).

PMID- 19757560
TI  - Effect of clindamycin hydrochloride on oral malodor, plaque, calculus, and
      gingivitis in dogs with periodontitis.
AB  - Periodontal disease is considered the most common disease of dogs and cats. The
      clinical sign most frequently reported by clients is oral malodor. Clindamycin
      hydrochloride has been used for several years for the treatment of periodontal
      disease in both cats and dogs. This study was designed to assess the effect of
      clindamycin HCl when used in two different post-prophylaxis treatment regimens on
      oral malodor and periodontal disease in a controlled clinical trial. This study
      demonstrated that a 5-day postprophylaxis regimen was significantly effective in
      reducing oral malodor compared with a dental prophylaxis alone. Clindamycin HCl
      significantly reduced oral malodor from the animals' baseline levels through 42
      days. In addition, although no effect was observed on periodontal pocket depth,
      this treatment regimen also resulted in significant reductions in dental plaque,
      dental calculus, and gingival bleeding.

PMID- 19757561
TI  - Satiety reduces adiposity in dogs.
AB  - The study reported here investigated the effect of satiety on body composition.
      Twelve beagle dogs were fed either a low-fiber (< 2%) or a high-fiber
      (approximately 20%) food that had previously been shown to cause differences in
      satiety. After 3 weeks the groups were fed the opposite food. Dogs were fed all
      they would voluntarily consume during one 45-minute meal per day. Each dog served
      as its own control. Although dogs consumed approximately equal amounts of food on
      a weight basis, they voluntarily ate significantly fewer calories (27% less) when
      fed the high-fiber food. Dogs lost four times as much fat mass when fed the high
      fiber food versus when fed the low-fiber food. Therefore this study indicates
      that foods enhanced with fiber increase satiety and reduce adiposity.

PMID- 19757562
TI  - Effects of a 1% hydrocortisone conditioner on hematologic and biochemical
      parameters, adrenal function testing, and cutaneous reactivity to histamine in
      normal and pruritic dogs.
AB  - The purpose of this double-blind study was to examine the effects of a 1%
      hydrocortisone, leave-on conditioner on hematologic and biochemical parameters,
      adrenal function tests, and cutaneous reaction to serial dilutions of histamine
      phosphate in healthy dogs and those with pruritic dermatitis. Groups 1 and 2 each
      consisted of eight healthy dogs. Seven pruritic dogs comprised Group 3. All dogs
      were bathed twice weekly for 6 weeks. Groups 1 and 3 had 1% hydrocortisone
      conditioner applied after each bath. Group 2 had vehicle from the conditioner
      applied after each bath. The amount of 1% hydrocortisone applied to the treated
      dogs ranged from 278 to 416 mg/m2. Hematologic and biochemical analysis and
      adrenocorticotrophic hormone (ACTH) stimulation tests were performed on all dogs
      on days 0,14, 28, and 42. Mean values for all blood and serum parameters remained
      within normal limits during the study. Post-ACTH cortisol levels were definitely
      lower in Group 3 than in Groups 1 and 2 on day 42 (P < 0.05) and when averaged
      over all days of the study (P < 0.05 and P < 0.01, respectively). Serum alkaline
      phosphatase levels were significantly lower in Group 3 on day 0 than on days 14
      (P < 0.05), 28 (P < 0.01), and 42 (P = 0.05). All dogs received intradermal
      injections of buffered saline and five serial dilutions of histamine phosphate on
      days 0, 14, 28, and 42. No significant differences were apparent among the groups
      in subjective and objective evaluation of intradermally injected dilutions of
      histamine. In this study, the use of a 1% hydrocortisone, leave-on conditioner
      did not result in clinically evident adverse effects, and only minor changes in
      blood parameters were detected. Although mean values in all groups remained
      within reference ranges throughout the study, the finding of statistically
      significant lower post-ACTH cortisol concentrations in the pruritic dogs (Group
      3) suggests that absorption of hydrocortisone may have occurred. The results of
      this study also show that this product does not significantly suppress cutaneous
      reactivity to histamine in normal and pruritic dogs.

PMID- 19757563
TI  - Efficacy of two canine parvovirus vaccines for inducing seroconversion in
      Rottweiler and Doberman pinscher pups with various levels of maternally derived
      antibodies.
AB  - The study reported here investigated the efficacy of two commonly used modified
      live virus vaccines to induce seroconversion against canine parvovirus (CPV) in
      213 Rottweiler and Doberman pinscher pups with various titers of maternally
      derived CPV antibody. Beginning at 6 to 8 weeks of age, pups were given a
      subcutaneous vaccination every 21 days (range, 18-24 days) in the dorsal region
      of the neck or shoulder area. Pups vaccinated with vaccine A(a) received three
      vaccinations and completed the vaccination series by 12 to 14 weeks of age. Pups
      vaccinated with vaccine Bb received four vaccinations and completed the
      vaccination series by 15 to 17 weeks of age. Antibody titers against CPV in both
      vaccine groups were similar before vaccination. Pups in the vaccine-A group
      seroconverted significantly earlier than those in the vaccine-B group. After the
      first vaccination, more pups with a CPV-2b hemagglutination inhibition (HI) titer
      of < or = 1:80 responded to vaccine A than to vaccine B. In addition, CPV-2b HI
      titers after vaccination were also significantly (P < or = 0.05) higher for the
      pups in the vaccine-A group after first, second, and third vaccinations, compared
      with those of pups in the vaccine-B group.

PMID- 19757564
TI  - Evaluation in vitro of the antimicrobial activity of two topical preparations
      used in the management of ear infections in the dog.
AB  - Products designed for ear cleansing (i.e., Epi-Otic and Epi-Otic New Formula
      [NF]a) were evaluated in vitro for their ability to kill clinical isolates of
      Staphylococcus intermedius, Pseudomonas aeruginosa, and the yeast Malassezia
      pachydermatis. Dilutions of the products at 1/5 and 1/25 in distilled water were
      inoculated with suspensions of the organisms and held at room temperature. The
      mixtures were sampled at intervals between 1 and 16 minutes, and numbers of
      viable colony-forming units of the microorganisms were determined by culture on
      blood agar or modified Dixon's agar (for the yeast) using the spread-plate
      method. At a dilution of 1/5, both products were able to eliminate S. intermedius
      within 1 minute. P. aeruginosa was eliminated within 2 minutes by both products.
      M. pachydermatis was eliminated by Epi-Otic NF and Epi-Otic within 4 and 8
      minutes, respectively. Lower activity was demonstrated following dilution at
      1/25. The findings support previously published data for Epi-Otic indicating
      antimicrobial activity both in vitro and in vivo. The findings suggest that Epi
      Otic may be useful in the control of ear infections.

PMID- 19757565
TI  - Response to modified live and killed multivalent viral vaccine in regularly
      vaccinated, fresh dairy cows.
AB  - Vaccination programs for viral pathogens in the dairy industry span the full
      spectrum of possibilities even though few of these have been evaluated in field
      situations. One such program is the vaccination of fresh cows 30 to 60 days
      postpartum with modified live viral (MLV) vaccines. The purpose of this study was
      to evaluate the antibody response to booster vaccinations during this period. The
      impact of vaccinations on milk production and reproductive performance was also
      examined. The response of cattle boosted with MLV bovine viral diarrhea virus
      (BVDV) was greatly enhanced compared with the saline controls and the killed
      vaccine test group. Similar increases were not seen with the MLV infectious
      bovine rhinotracheitis virus (IBR) and bovine respiratory syncytial virus (BRSV).
      Changes in milk production were not detected. There was a positive effect on the
      rate of conception with the MLV group even though there was no evidence of the
      presence of the three viruses in the herd at the time of study. Although this was
      a single field trial, and thus limited in scope and repeatability, the results
      indicate that the vaccines used had a positive effect.

PMID- 19757566
TI  - Salmonella derby cross-protection study.
AB  - An avirulent live (AVL), Salmonella choleraesuis vaccine (Salmo Shield Live
      [Grand Laboratories, Inc.]) was administered to pigs at weaning or 3 weeks of
      age. Two weeks after vaccination the vaccinated pigs as well as unvaccinated
      control pigs were challenged intranasally with a commonly isolated environmental
      Salmonella serotype, S. derby. At 2, 4, and 6 weeks after challenge, pigs were
      euthanized and cultured for S. derby. Although the number of pigs in this study
      was too small to draw any definite generalizable conclusions, the vaccinated pigs
      had significantly reduced reisolation rates of S. derby when compared with the
      control pigs. Further research in this area is needed.

PMID- 19757567
TI  - A Scoring Index for Clinical Signs of Flea Allergy Dermatitis in the cat.
AB  - This article describes the development, application, and validation of a scoring
      index for assessment of clinical signs in cats with flea allergy dermatitis
      (FAD). The Scoring Index for Clinical Signs of FAD was based on the evaluation
      and scoring of five signs over five anatomic areas, which is similar to the
      psoriasis area and severity index (PASI), a commonly used scoring method in human
      dermatology. The Scoring Index for Clinical Signs of FAD was used by different
      veterinarians to assess several groups of flea allergic research cats with
      varying signs of FAD. Analysis of the data shows a significant correlation and
      repeatability between investigators, making this a very useful scoring index.

PMID- 19757568
TI  - Comparison of bovine herpesvirus 1 vaccines for rapid induction of immunity.
AB  - The purpose of the study reported here was to compare four different vaccine
      regimens for their efficacy in protecting calves from challenge with bovine
      herpesvirus 1 (BHV1) at 5 and 14 days after vaccination. Nine experimental groups
      of five calves each were used to compare four vaccination regimens and a group
      that received no vaccine. The four vaccine regimens were: a BHV1 intramuscular
      (IM) vaccine containing both modified live virus (MLV) and killed virus (KV); an
      MLV intranasal (IN) vaccine; concurrent administration of MLV IN vaccine and MLV
      IM vaccine; and concurrent administration of MLV IN vaccine and KV vaccine. All
      vaccine regimens induced solid protection against BHV1 challenge at 14 days after
      vaccination. All of the vaccine regimens also induced statistically significant
      (P < .05) protective immunity at 5 days after vaccination; however, there were
      significant differences (P < .05) in the degree of protection. The best
      protection induced by 5 days after vaccination was provided by the MLV + KV
      combination vaccine injected IM and the MLV vaccines given IN and IM
      concurrently. The MLV + KV combination vaccine administered IM gave significantly
      (P < .05) better protection by 5 days after vaccination than the MLV vaccine
      administered IN. Administering a KV BHV1 vaccine IM at the same time as the MLV
      BHV1 IN vaccine significantly (P < .05) reduced the effectiveness of the IN
      vaccine for inducing early protective immunity.

PMID- 19757569
TI  - Comparative evaluation of the speed of flea kill of imidacloprid and selamectin
      on dogs.
AB  - Imidacloprid (Advantage, Bayer Corporation, Shawnee Mission, KS) and selamectin
      (Revolution [United States], Pfizer Animal Health, Exton, PA 19341; Stronghold
      [European Union], Pfizer Animal Health Ltd, Sandwich, Kent CT 13 9NJ, UK) were
      tested to assess the speed of flea kill achieved against existing flea
      infestations and subsequent reinfestations. Thirty-six dogs were infested with
      100 unfed adult fleas on day-1. On day 0, 12 dogs (group 1) were treated with
      imidacloprid at the minimum label dose of 10 mg/kg body weight. Twelve dogs
      (group 2) were treated with selamectin at the minimum label dose of 6 mg/kg body
      weight. Twelve dogs (group 3) remained as untreated controls. Four sub-groups (A
      through D) of three dogs each were designated within each group. All dogs were
      subsequently reinfested with fleas on days 6, 13, 20, 27, 34, and 41. Live flea
      counts were performed for subgroups A through D at 6, 12, 24, and 36 hours after
      treatment/reinfestation. Imidacloprid provided significantly and consistently
      greater flea kill than selamectin at 6, 12, and 24 hours after treatment and at 6
      and 12 hours after each reinfestation. Although both products are commercially
      labeled for monthly topical use, imidacloprid provided significantly greater 36
      hour flea kill at 34 and 41 days after treatment.

PMID- 19757570
TI  - Hypokalemia, muscle weakness, and recumbency in dairy cattle.
AB  - Seventeen cases of severe hypokalemia (serum or plasma potassium < or = 2.1
      mEq/L) in association with profound muscle weakness and recumbency in lactating
      dairy cattle were included in a retrospective study. The cattle were from 15
      different farms. Eleven of the 17 animals were recumbent at presentation while
      the remaining six became recumbent within 6 hours of admission. Both multiparous
      cows (n = 11) and first calf heifers (n = 6) were included. The median days in
      milk was 21 (range: 5 to 110), and chronic, recurrent ketosis (15 of the 17
      cases) was the most common preexistent condition. Potential musculoskeletal and
      neurologic causes of recumbency were ruled out on the basis of physical
      examination and ancillary diagnostics. Ten of the 17 animals were euthanized and
      underwent full necropsy examination that demonstrated ischemic muscle damage and
      varying degrees of hepatic lipidosis. Aggressive potassium supplementation was
      instituted in all 17 cases either orally, intravenously, or by a combination of
      both routes. In the seven individuals that survived, potassium supplementation
      was administered orally and intravenously in five, orally only in one, and
      intravenously only in one.

PMID- 19757571
TI  - A 10-day toxicity study of toltrazuril 5% suspension in the horse.
AB  - Equine protozoal myeloencephalitis (EPM) is a serious disorder of the nervous
      system of horses caused by Sarcocystis neurona. Recently, toltrazuril has begun
      to be used for treatment of EPM. The purpose of this study was to evaluate the
      potential toxicity of toltrazuril in horses when administered at a dose of 50
      mg/kg for 10 days. Five horses were given 50 mg/kg of toltrazuril once daily for
      10 days by nasogastric tube. Complete blood cell counts, serum chemistry values,
      and coagulation panels were evaluated before and after treatment; then a full
      postmortem examination was completed on day 11. Results of the study show that
      only mild clinical signs (i.e., anorexia, weight loss, and colic in one of the
      five horses) were observed after treatment. Minimal changes were noted in the
      serum chemistry analysis (i.e., increased bilirubin and serum protein, mildly
      increased hematocrit and hemoglobin concentration, and mildly increased albumin).
      Renal medullary congestion was noted on gross postmortem examination; however, no
      microscopic changes due to compound administration were noted in the kidneys or
      other tissue. Results of this study suggest that administration of toltrazuril at
      50 mg/kg (5x to 10x anticipated clinical dosage) for 10 days resulted in only
      mild clinical abnormalities.

PMID- 19757572
TI  - Clinical efficacy of selamectin for the control of fleas on dogs and cats.
AB  - The topical endectocide selamectin (Revolution, Pfizer Animal Health) was
      evaluated in seven veterinary dermatology specialty clinics for its ability to
      control fleas on 75 dogs and 46 cats from single- and multiple-animal households.
      All animals were treated on days 0, 30, and 60 with a minimum unit dose of 6
      mg/kg of selamectin(h) applied to the skin in a single spot at the base of the
      neck in front of the scapulae. The product was applied according to label
      instructions, and the use of other topical or environmental flea control products
      was prohibited during the study. Efficacy was assessed by percentage reductions
      in geometric mean flea comb counts. The reductions in flea numbers for dogs and
      cats combined were 90.6%, 97.0%, and 98.0% on days 30, 60, and 90, respectively,
      compared with day 0. This study demonstrates that selamectin, applied at 30-day
      intervals to dogs and cats, effectively controls flea infestations without other
      flea control products in single- and multiple-animal households.

PMID- 19757573
TI  - Evaluation of in vitro activity of two topical products against three organisms
      isolated from canine referral patients with otitis externa and cutaneous
      pyoderma.
AB  - Canine otitis externa and cutaneous pyoderma are common problems that are often
      associated with Staphylococcus intermedius, Pseudomonas aeruginosa, and
      Malassezia pachydermatis. In vitro activity of two topical products against these
      organisms isolated from canine referral patients were evaluated. Organisms were
      grown and diluted to a concentration equivalent to 10(7) colony-forming units
      (CFU) per mL and exposed to either a 0 or 1/5 dilution of Hexadene Flush with
      Spherulites (Virbac Animal Health Inc, Fort Worth, TX) or a 1/5 or 1/25 dilution
      of ResiCHLOR Lotion with Spherulites (Virbac Animal Health Inc, Fort Worth, TX)
      at time intervals from 1 to 30 minutes. Results showed that all three organisms
      were killed within 1 minute of contact time at 0 and 1/5 dilution of the flush.
      The lotion diluted to 1/5 also killed all three organisms. At 1/25 dilution, this
      lotion killed S. intermedius and P. aeruginosa within 1 minute of contact time,
      whereas M. pachydermatis was killed after 1 minute. The findings suggest that the
      two topical products exhibit efficacy against these common skin pathogens in
      vitro and can be useful in their clinical management.

PMID- 19757574
TI  - Effect of increasing dietary antioxidants on concentrations of vitamin E and
      total alkenals in serum of dogs and cats.
AB  - Oxidative damage to DNA, proteins, and lipids has been implicated as a
      contributor to aging and various chronic diseases. The presence of total alkenals
      (malondialdehyde and 4-hydroxyalkenals) in blood or tissues is an indicator of
      lipid peroxidation, which may be a result of in vivo oxidative reactions. Vitamin
      E functions as a chain-breaking antioxidant that prevents propagation of free
      radical damage in biologic membranes. This 6-week dose-titration study was
      conducted to assess the effect of selected dietary vitamin E levels on byproducts
      of in vivo oxidative reactions in dogs and cats. Forty healthy adult dogs and 40
      healthy adult cats were assigned to four equal groups per species in a complete
      random block design. A control group for both dogs and cats was fed dry food
      containing 153 and 98 IU vitamin E/kg of food (as fed), respectively. Canine and
      feline treatment groups were fed the same basal dry food with vitamin E added at
      three different concentrations. The total analyzed dietary vitamin E levels for
      the canine treatment groups were 293, 445, and 598 IU vitamin E/kg of food, as
      fed. The total analyzed dietary vitamin E levels for the feline treatment groups
      were 248, 384, and 540 IU vitamin E/kg of food, as fed. Increasing levels of
      dietary vitamin E in dog and cat foods caused significant increases in serum
      vitamin E levels compared with baseline values. Although all treatments increased
      concentrations of vitamin E in serum, all were not effective at decreasing serum
      alkenal levels. The thresholds for significant reduction of serum alkenal
      concentrations in dogs and cats were 445 and 540 IU vitamin E/kg of food,
      respectively, on an as-fed basis. The results of this study show that normal dogs
      and cats experience oxidative damage and that increased dietary levels of
      antioxidants may decrease in vivo measures of oxidative damage.

PMID- 19757575
TI  - Efficacy of 65% permethrin applied as a topical spot-on against walking dandruff
      caused by the mite, Cheyletiella yasguri in dogs.
AB  - The efficacy of a 65% permethrin topically applied spot-on formulation (Defend
      EXspot Topical Remedy for Dogs, Schering-Plough Animal Health, Union, NJ) was
      determined against the dog mite, Cheyletiella yasguri (Smiley, 1965). Female dogs
      and their litters comprised the experimental unit, and all dogs in an
      experimental unit were treated on the same day 4 to 6 weeks after whelping. Mites
      and mite eggs were counted weekly on an untreated control group of six litters
      (15 pups) and on a group of six litters (14 pups) treated with 65% permethrin.
      Pups in the untreated control group maintained high numbers of Cheyletiella
      yasguri throughout the 14- to 21-day observation period. No mites or mite eggs
      were detected on dogs within 7 to 21 days after application of 65% permethrin. No
      adverse reactions were noted during the study. Clinical signs of infestation with
      C. yasguri--which included skin irritation, thickening of the stratum corneum,
      scratching with resultant scabs, pruritus, and flaky, scaly skin-were eliminated
      when mites were killed by the 65% permethrin formulation.

PMID- 19757576
TI  - Double-blind, placebo-controlled study to evaluate two miconazole conditioners
      for the treatment of Malassezia dermatitis in dogs.
AB  - Eighteen dogs with Malassezia dermatitis participated in a clinical trial to
      evaluate the efficacy of miconazole conditioners. Dogs were randomly assigned to
      receive vehicle only, miconazole 1%, or miconazole 2% conditioner. Conditioners
      were used three times weekly for 2 weeks and then twice weekly for 2 weeks.
      Investigators evaluated erythema, pruritus, and yeast counts weekly. Owners
      scored pruritus daily. Yeast number decreased in all treatment groups. Yeast
      number in the vehicle group was higher than in both the miconazole treatment
      groups but was not different between the two miconazole groups. Clinical scores
      decreased but no difference was detected among groups.

PMID- 19757577
TI  - Effects of treatment with clindamycin hydrochloride on progression of canine
      periodontal disease after ultrasonic scaling.
AB  - This study was conducted to determine the benefit, if any, of combining
      antibiotic therapy with ultrasonic scaling, root planing, and polishing (USRP)
      over USRP alone as determined by improvements in plaque index, gingival index,
      and pocket depth measurements. Thirty dogs with signs of periodontal disease were
      randomly assigned to the USRP-only treatment group or to the USRP-antibiotic
      treatment group. USRP was performed on all dogs on study day 0. In addition, dogs
      in the USRP-antibiotic treatment group received clindamycin hydrochloride
      (Antirobe, Pharmacia & Upjohn, Kalamazoo, MI) dosed at 2.5 mg/lb body weight (BW)
      twice a day beginning on day 0 and continuing 8 days. Followup visits occurred 2,
      6, 13, and 25 weeks after the start of the study. Treatment differences were
      compared using a mixed model analysis for repeated measures. This analysis
      indicated that the clindamycin regimen, after USRP, had a significant effect on
      plaque and pocket depth measures of periodontal disease but not on gingivitis.
      For plaque, average index scores for the treatment group were lower at all follow
      up visits with significant differences at 2 and 6 weeks after cleaning. The
      antibiotic treatment group also maintained a significantly smaller average pocket
      depth, representing a 15% postcleaning reduction for the clindamycin group versus
      a 3% reduction in the control group.

PMID- 19757578
TI  - Repellency and efficacy of 65% permethrin and 9.7% fipronil against Ixodes
      ricinus.
AB  - Two topically applied spot-on products--65% permethrin (Defend Exspot Treatment
      for Dogs, Schering-Plough Animal Health, Union, NJ) and 9.7% fipronil (Frontline
      Spot On Dog, Merial Limited, Iselin, NJ)--used for canine flea and tick control
      were evaluated for repellency against Ixodes ricinus, the tick species that is
      the primary vector of Lyme disease in Europe. Eighteen dogs were randomly
      assigned to the following treatment groups (n = 6): (1) 65% permethrin, (2) 9.7%
      fipronil, or (3) untreated control. Dogs were exposed to ticks in individually
      assigned cages with a carpet that covered =70% of the cage bottom. Dogs in
      treatment groups 1 and 2 were treated in accordance with label directions for
      each re-spective product on study day 0. Fifty unfed, male and female adult ticks
      were placed in the cages 15 to 30 minutes before the dogs. The dogs were placed
      in the cages for a 2-hour exposure period at 2, 7, 14, 21, 28, 35, and 41 days
      after treatment. After a 2-hour exposure period, dogs were removed from the cages
      and live (attached and unattached) and dead ticks were counted on the dogs, on
      the carpets, and in the cages. Cages were thoroughly cleaned and new carpet was
      used for each tick exposure period. Treatment of dogs with 65% permethrin reduced
      tick numbers on dogs by 99.1% at 2 days, 99.0% at 1 week, 95.9% at 2 weeks, 88.5%
      at 3 weeks, 87.1% at 4 weeks, and 48.0% at 6 weeks after application. In
      contrast, treatment of dogs with 9.7% fipronil reduced tick numbers on dogs by
      61.4% at 2 days, 51.6% at 1 week, 37.0% at 2 weeks, 33.7% at 3 weeks, 10.8% at 4
      weeks, and 0% at 6 weeks after application. The efficacy of 65% permethrin was
      significant (P < or = .05) when compared to the control at all challenges,
      whereas the efficacy of 9.7% fipronil was not significant as compared to controls
      at 21, 28, 35, and 41 days after treatment. The 65% permethrin killed
      significantly more Ixodes ricinus ticks (P < or = .05) than 9.7% fipronil from 2
      to 41 days after treatment. The 65% permethrin repelled 1.9-, 2.0-, 3.0-, 43.3-,
      3.9-, 8.9-, and 17.3-fold more Ixodes ricinus than did 9.7% fipronil at 2, 7, 14,
      21, 28, 35, and 41 days after treatment, respectively, and all differences in
      repellency were significant (P < or = .05).

PMID- 19757579
TI  - Prevalence of exposure to Dirofilaria immitis in cats in multiple areas of the
      United States.

PMID- 19757580
TI  - Feline heartworm disease: correlations of clinical signs, serology, and other
      diagnostics--results of a multicenter study.
AB  - In cooperation with 15 practices in Florida, South Carolina, Tennessee, and
      Texas, data were collected on 215 cats with signs consistent with feline
      heartworm disease (FHD). Cats included in the study were over 6 months of age and
      presented with primary complaints of coughing or dyspnea, vomiting unrelated to
      eating, or acute death. Detailed signalment, thoracic radiographs, CBC, Knott or
      DIFIL test, DiroCHEK antigen test (Ag), and antibody (Ab) tests performed by
      Animal Diagnostics (AD) and Heska Corp (HC) were collected on each cat. Any cat
      that had positive antibody or antigen tests, and any cat with radiographic signs
      suggestive of FHD was scheduled for recheck examinations at 30 to 45 days and/or
      60 to 90 days after initial presentation. This study was designed to identify
      cats with concurrent or previous FHD, and to better characterize the presentation
      of this disease by following their progress. Of the 215 cats, 94 (44%) were Ab
      positive based on one or both tests. This indicated that the cat had been
      successfully infected with third-stage heartworm larvae and those larvae had
      developed to at least the fourth stage. Of the Ab-positive cats, 23/94 (24%)
      presented with vomiting; 39/94 (41%) presented with respiratory signs; and 27/94
      (29%) had vomiting and respiratory signs. Discordant results between the AD and
      HC antibody tests occurred, with the AD test detecting a higher number of
      antibody-positive cats. When comparing results of these Ab tests, no correlation
      was seen between the intensity of Ab level measured by the two tests, suggesting
      that different Ab is detected. One cat that died acutely with signs associated
      with FHD had relatively low Ab detected on both tests but had a positive DiroCHEK
      antigen test. No correlation between the level of antibody and the severity of
      clinical signs or radiographic pattern was found. Eleven cars were DiroCHEK Ag
      positive on initial presentation. Of the Ag-positive cats, 2 were AD negative and
      3 were HC negative. One cat was Ag positive and microfilaria positive but
      negative for Ab with both AD and HC tests. Although it has been presumed that
      most cats with FHD are Ag negative, it would appear that some individual cats
      with adult heartworms can also be Ab negative. Although eosinophilia and
      basophilia were more frequently associated with cats that were Ab positive,
      abnormal CBC values were observed in cats that were currently Ab negative.
      Radiographic lesions did not correlate with clinical signs or Ab levels. Some
      cats with no radiographic signs of FHD were Ag positive. Further, some cats with
      typical radiographic lesions of FHD were negative based on all serologic
      evaluations. These results demonstrate that successful transmission of heartworms
      to cats is more common than previously thought and is clinically associated with
      coughing, dyspnea, and vomiting. A cause and effect correlation cannot be proven
      between clinical signs and laboratory evaluation. Radiographic evidence of FHD in
      cats with repeated negative antibody results may be an indicator of residual
      damage from previous heartworm infections. Most experimental studies of FHD have
      been short-term (< 1 yr). However, in this study, many cats underwent repeated
      clinical evaluation over a relatively short time. This demonstrated that the
      clinical picture of spontaneous FHD is a constantly changing syndrome, highly
      dependent on the stage (immature L5, adult, adult death, residual damage) of the
      parasite in the cat and the individual cat's response. On evaluation of
      clinically affected cats, no one test proved to be definitive (without
      exceptions). The diagnosis of FHD continues to require a combination of clinical
      evaluation and a series of diagnostic tests, often requiring reevaluations over
      time.

PMID- 19757581
TI  - Immune responses and efficacy after administration of a commercial Brucella
      abortus strain RB51 vaccine to cattle.
AB  - Brucella abortus strain RB51 (SRB51) is a newly approved live vaccine to protect
      cattle against brucellosis. The purpose of this study was to evaluate the
      immunologic responses of cattle to a commercially available SRB51 vaccine and to
      characterize the efficacy of the vaccine to protect against abortion or infection
      after midgestational challenge with virulent B. abortus strain 2308 (S2308). All
      cattle were pasture bred, and pregnancy was confirmed by rectal palpation.
      Pregnant cattle were intraconjunctivally challenged with 1 x 10(7) colony-forming
      units (CFUs) of S2308 at 180 days gestation. Serologic responses were monitored
      in all heifers after vaccination using the standard tube agglutination test and a
      dot-blot assay using killed SRB51 as antigen. In one study, 3-month-old Hereford
      heifers were subcutaneously inoculated with 10(9) CFU or 10(10) CFU of a
      commercially available SRB51 vaccine or 2 mL of 0.15M sodium chloride (saline).
      In this study, four of eight nonvaccinates, two of four 10(9) CFU SRB51
      vaccinates, and two of 14 10(10) CFU SRB51 vaccinates aborted after
      midgestational challenge with virulent S2308. The challenge strain was recovered
      at necropsy from maternal or fetal tissue from six of nine nonvaccinates, four of
      four 10(9) CFU SRB51 vaccinates, and seven of 14 heifers vaccinated with 10(10)
      CFU of SRB51. In a separate study, 6-month-old Hereford heifers were
      subcutaneously inoculated with 10(10) CFU of SRB51 or saline. Peripheral blood
      mononuclear cells proliferative responses to gamma-irradiated SRB51 were
      monitored. In this study, three of seven nonvaccinates and one of 18 10(10) CFU
      SRB51 vaccinates aborted. The S2308 challenge strain was recovered from maternal
      or fetal tissue of five of seven nonvaccinates and seven of 18 SRB51 vaccinates.
      In both studies, cattle vaccinated with 10(10) CFU of SRB51 had greater (P < .05)
      antibody responses to SRB51 at 4 and 8 weeks after vaccination than
      nonvaccinates. SRB51-vaccinated cattle had greater lymphocyte proliferative
      responses to killed SRB51 at 10, 12, 14, and 16 weeks when compared with
      nonvaccinates. The data presented in this study indicate that 10(10) CFU of the
      commercial SRB51 vaccine was highly efficacious (P < .02) in preventing Brucella
      induced abortion or fetal infection. Considering that fetal infection and
      abortion are the predominant mechanisms for transmission of brucellosis, our data
      suggest that the commercially available SRB51 vaccine will be efficacious in
      preventing abortion and controlling brucellosis in cattle under field conditions.
      However, incidence of maternal infection with Brucella at necropsy did not differ
      (P > .05) among 10(10) CFU SRB51 vaccinates and nonvaccinates.

PMID- 19757582
TI  - Comparison of ivermectin SR bolus, benzimidazole anthelmintics, and topical
      fenthion on productivity of stocker cattle from grazing through feedlot.
AB  - A study was conducted to determine the effect of different parasite control
      programs on weight gain and other measurements for stocker beef calves during the
      grazing season and subsequent feedlot phase of production. One hundred eighty
      recently weaned beef steers were purchased from a Mississippi sale barn and were
      allocated by restricted randomization on pretreatment weight to three treatments:
      (1) no anthelmintic treatment; treated only with a topical organophosphate (OP)
      during processing into the feedlot; (2) one benzimidazole (BZD) treatment at
      initiation of grazing, and a second given at the time of processing upon arrival
      at the feedlot, along with a topical OP; and (3) ivermectin sustained-release
      (SR) bolus administered at initiation of grazing, with no further treatment given
      at the feedlot. The cattle grazed separately by treatment for 125 days, with six
      replicated pastures per treatment; then were penned according to the same
      groupings after entry into the feedlot on day 127. Cattle were individually
      weighed at approximately 2-month intervals, and feed consumption was measured
      during the 167 days in the feedlot. Fecal nematode egg counts were individually
      monitored for all animals during both phases of the trial. Carcass weight,
      quality grade, yield grade, and the incidence of liver abscesses were recorded
      for each animal at slaughter. Cattle treated with the ivermectin SR bolus gained
      significantly (P < .05) more weight through the grazing period and from the start
      of grazing through the end of the feedlot phase than the controls or the cattle
      treated with BZD products. There were no significant differences in feed
      efficiency between any of the groups. Mean carcass weight for cattle treated with
      boluses was significantly (P < .05) greater than that of the controls and the
      group treated with BZD. Dressing percentage and quality grade were significantly
      (P < .05) higher for the BZD and bolus groups, and yield grade was slightly (but
      not significantly) better for each of these groups than for controls.
      Significantly (P < .05) fewer livers of cattle treated with boluses had abscesses
      at slaughter than did livers of controls or cattle treated with BZDs. During both
      phases of the trial, fecal egg counts were significantly (P < .05) lower for the
      group treated with boluses than for the untreated group or the group treated with
      BZD. These data indicate that treatment with boluses for parasite control at the
      beginning of the grazing period had beneficial effects on weight gain as compared
      to no anthelmintic treatment or treatment with a BZD at the start of grazing and
      again at the time of introduction into the feedlot. These bolus benefits were
      sustained through the feedlot phase of production and provided further
      improvements with significantly (P < .05) increased carcass weights. The bolus is
      a tool that can significantly increase the efficiency of production for cattle
      producers who retain ownership into the feedlot phase of production or feedlot
      operators who graze stockers before feedlot entry.

PMID- 19757584
TI  - George Porter (1920-2002): kinetics research and the public understanding of
      science.

PMID- 19757583
TI  - Antibiotic sensitivity of an Argentine strain collection of Moraxella bovis.
AB  - The antimicrobial susceptibility of 88 isolates of Moraxella bovis of Argentine
      origin was evaluated for 12 antimicrobials by broth microdilution procedures. The
      isolates had a minimum inhibitory concentration (MIC90) of < or = 0.06 microg/mL
      to enrofloxacin; < or = 0.12 microg/mL to ceftiofur; < or = 0.25 microg/mL to
      ampicillin; < or = 0.5 microg/mL to florfenicol and gentamicin; < or = 1.0
      microg/mL to tilmicosin, erythromycin, and oxytetracycline; < or = 4.0 microg/mL
      to tylosin; < or = 8.0 microg/mL to spectinomycin; < or = 0.25/4.75 microg/mL to
      trimethoprim/sulfamethoxazole; and > or = 32 microg/mL to lincomycin. Modal MIC
      values for these antimicrobials were as follows: enrofloxacin, 0.03 microg/mL;
      ceftiofur, 0.06 pg/mL; ampicillin, 0.25 microg/mL; florfenicol, gentamicin,
      erythromycin, and oxytetracycline, 0.5 microg/mL; tilmicosin, 1.0 microg/mL;
      tylosin and spectinomycin, 4.0 microg/mL; lincomycin and erythromycin, 16
      microg/mL; and trimethoprim/ sulfamethoxazole, < or = 0.25/4.75 microg/mL. These
      data show that all antimicrobials except lincomycin have MICs suggestive of
      sensitivity in vitro, though confirmation of clinical efficacy can only be
      properly assessed based on pharmacologic and/or clinical data to support the MIC
      values.

PMID- 19757585
TI  - Welding, organizing, and planting organic molecules on substrate surfaces-
      promising approaches towards nanoarchitectonics from the bottom up.

PMID- 19757586
TI  - Bistable electrical, optical, and magnetic behavior in a molecule-based material.

PMID- 19757587
TI  - Hadamard transform time-of-flight mass spectrometry: more signal, more of the
      time.
AB  - Hadamard transform time-of-flight mass spectrometry (HT-TOF MS) is a type of mass
      analysis that was developed to couple continuous ion sources to the inherently
      pulsed nature of time-of-flight measurements. Unlike conventional TOF MS, the
      Hadamard transform method offers a duty cycle of 50%, with the possibility of
      extending it to 100%. Because it is a multiplexing technique, the attainable
      signal-to-noise ratio (SNR) is also significantly higher than that of
      conventional TOF MS. This review covers the basic principles behind HT-TOF MS. We
      illustrate, through examples, the source of the high-duty cycle and the increase
      in SNR. These features translate to a mass spectral storage rate that is the
      fastest among similar instruments, which enables its use as a detector for high
      speed separations.

PMID- 19757588
TI  - Gelsemine: a thought-provoking target for total synthesis.
AB  - Gelsemine and 21-oxogelsemine have been synthesized through several routes. This
      Review focuses on the comparison of the different strategies to assemble the
      bicyclo[3.2.1]octane core, to introduce the bridgehead quaternary C20 to form the
      pyrrolidine moiety, to construct the oxindole residue, and to close the
      tetrahydropyran ring en route to gelsemine.

PMID- 19757589
TI  - Thin-chip microspray system for high-performance Fourier-transform ion-cyclotron
      resonance mass spectrometry of biopolymers.

PMID- 19757590
TI  - Morphosynthesis of star-shaped titania-silica shells.

PMID- 19757591
TI  - Measurement of a Cu-Cu distance of 26 A by a pulsed EPR method.

PMID- 19757592
TI  - An efficient method for controlled propylene oxide polymerization: the
      significance of bimetallic activation in aluminum Lewis acids.

PMID- 19757593
TI  - Block-selected molecular recognition and formation of polypseudorotaxanes between
      poly(propylene oxide)-poly(ethylene oxide)-poly(propylene oxide) triblock
      copolymers and alpha-cyclodextrin.

PMID- 19757594
TI  - Aligning a single-lipid nanotube with moderate stiffness.

PMID- 19757595
TI  - Channels and cavities lined with interlocked components: metal-based
      polyrotaxanes that utilize pyridinium axles and crown ether wheels as ligands.

PMID- 19757596
TI  - Perfluorinated meso-aryl-substituted expanded porphyrins.

PMID- 19757597
TI  - A biomimetic synthesis of thiazolines using hexaphenyloxodiphosphonium
      trifluoromethanesulfonate.

PMID- 19757598
TI  - Hydrogen bonds around M(mu-O)2M rhombs: stabilizing a {CoIII(mu-O)2CoIII} complex
      at room temperature.

PMID- 19757599
TI  - Iridium-catalyzed Mizoroki-Heck-type reaction of organosilicon reagents.

PMID- 19757600
TI  - Activation of nitrous oxide and selective oxidation of alcohols and alkylarenes
      catalyzed by the [PV2Mo10O40]5(-) polyoxometalate ion.

PMID- 19757601
TI  - Probing specificity in carbohydrate-carbohydrate interactions with micelles and
      Langmuir monolayers.

PMID- 19757603
TI  - Synthesis and characterization of heterometallic {Cr7M} wheels.

PMID- 19757602
TI  - 1,2-Migration of the thio group in allenyl sulfides: efficient synthesis of 3
      thio-substituted furans and pyrroles.

PMID- 19757604
TI  - Novel T-shaped 14-electron platinum(II) complexes stabilized by one agostic
      interaction.

PMID- 19757606
TI  - The catalytic intermolecular orthoarylation of phenols.

PMID- 19757605
TI  - Reversible formation of iodosylbenzene-iron porphyrin intermediates in the
      reaction of oxoiron(IV) porphyrin pi-cation radicals and iodobenzene.

PMID- 19757607
TI  - Eta 6-germabenzene complexes of chromium and molybdenum.

PMID- 19757608
TI  - A diversity-oriented synthesis of alpha-amino acid derivatives by a
      silyltelluride-mediated radical coupling reaction of imines and isonitriles.

PMID- 19757609
TI  - Rats, mice, and germs.

PMID- 19757610
TI  - USDA hopes to continue current information collection practices; NIH finalizes
      data sharing rules.

PMID- 19757611
TI  - You can't go back--or can you?

PMID- 19757612
TI  - Nodular lesion on the eyelid of a dwarf rabbit. Malignant melanoma.

PMID- 19757613
TI  - Environmental monitoring: the key to effective sanitation.
AB  - Judicious and effective use of chemical decontaminants has a critical function in
      meeting the bioexclusion and biocontainment objectives established in every well
      managed animal research facility. The authors provide an overview of the
      components to consider when developing and implementing an environmental
      monitoring program.

PMID- 19757614
TI  - Quality assurance of animal watering systems.
AB  - Contaminants in the water supplied to laboratory animals pose a serious threat to
      both the health and welfare of the animals and the reliability of experimental
      data. The authors assess various systems for water purification, and suggest
      strategies for matching water quality assurance to the needs of the facility and
      its users.

PMID- 19757615
TI  - Rodent quality assurance testing: use of sentinel animal systems.
AB  - The ability to produce unique strains of genetically engineered mice has
      revolutionized biomedical research, but has also complicated the maintenance of
      "clean" facilities through an increase in the movement of animals between
      facilities and the production of immunodeficient strains. The authors discuss the
      use of sentinel and quarantine programs to minimize disease transmission between
      laboratory mice.

PMID- 19757616
TI  - Diagnostic testing of mouse and rat colonies for infectious agents.
AB  - Rodent health monitoring programs make an essential contribution to biomedical
      research by identifying the presence of infectious agents that might confound
      animal research. The authors discuss the types of diagnostic tests available,
      which agents deserve monitoring, and the appropriate frequency for such
      interventions.

PMID- 19757617
TI  - Rodent pain study lacked appropriate literature review.

PMID- 19757618
TI  - Comparison of three commercially available activated charcoal canisters for
      passive scavenging of waste isoflurane during conventional rodent anesthesia.
AB  - Chronic, low-level exposure to waste anesthetic gases has been linked to
      increased incidences of neurologic and reproductive dysfunction, hepatic and
      renal toxicity, and neoplasia in humans. We have shown previously that one brand
      of activated charcoal canister (F/Air) used for passive scavenging of halogenated
      gases does not completely remove isoflurane during anesthetic protocols used in
      conventional laboratory animal facilities. For the present study, we compared the
      scavenging capacities of three commercially available canister brands (Breath
      Fresh, EnviroPure, F/Air) using the same protocol. Well-maintained precision
      isoflurane vaporizers were equipped with two circuits (a nonrebreathing one
      hooked to a modified Bain facemask and the other to an induction box), each of
      which was attached to a canister. Isoflurane concentration and oxygen flow rate
      were set at 2% and 1 liter/min, respectively. Real-time atmospheric isoflurane
      emissions from canister exhaust ports were assessed using a portable infrared
      spectrophotometer. In a random survey of canisters that had not reached their
      maximal use life (specified by the manufacturers as a weight gain of 50 g), the
      percentage of canisters emitting > or = 5 ppm but < 100 ppm of waste isoflurane
      was 46% for Breath Fresh (n = 24), 8% for EnviroPure (n = 39), and 27% for F/Air
      (n = 37). Failure (defined as an isoflurane efflux of > or = 100 ppm) occurred in
      42% of Breath Fresh units but 0% for the other brands. In a subsequent experiment
      (n = 6/brand), all Breath Fresh and F/Air but no EnviroPure canisters had at
      least one reading of > or = 5 ppm by the time they gained 30 g. These data
      indicate that marked variability in gas-scavenging capacity exists between
      different brands of commercially available activated charcoal canisters and
      suggest that trace levels of waste isoflurane may occur in high-throughput
      laboratory animal anesthesia rooms unless canister exhaust also is captured.

PMID- 19757619
TI  - Successful management of long-term general anesthesia in rabbits used as an
      animal model of human disease.
AB  - The rabbit represents a popular animal model for basic science research, but
      projects requiring anesthesia and endotracheal intubation represent a technical
      challenge because of the difficulty in accessing the animal's airway and
      sensitivity to common anesthetic agents. We hypothesized that transoral
      intubation under direct visualization with guidewire assistance would improve
      airway access success and reduce perioperative mortality in the rabbit. Of the 39
      New Zealand White rabbits that had passive inhalation anesthesia and were
      intubated using wire-guided assistance under direct laryngeal visualization, 33
      were intubated using a flexible wire after the rigid guide had resulted in airway
      injury in three of the first six rabbits. Animals were then maintained under
      general anesthesia during a 4- to 5-h procedure. At the completion of the
      procedure, animals were recovered from anesthesia and extubated. All 39 animals
      were successfully intubated, mostly on the first attempt. There were two animal
      deaths, both in the first six animals; one death was a direct result of laryngeal
      injury from the rigid wire guide initially used. One additional animal in the
      first six had pulmonary difficulty after an airway injury but recovered and was
      successfully used in the experiment. Two animals developed gastric distention
      during anesthesia, which was alleviated with placement of an orogastric tube
      without adverse sequelae. No animals developed problems with oxygenation during
      the experiment, but over half (52.8%) had end-tidal CO2 (ETCO2) above 45 mmHg at
      least once during the surgery, and 13 rabbits were above this level for longer
      than 1 h. An average of 18 min elapsed between withdrawal of anesthesia and the
      time when spontaneous respirations and chewing movements returned. Animals then
      could be safely extubated. There was no correlation between high perioperative
      ETCO2 and time to recovery from anesthesia (P = 0.18, r = 0.23).

PMID- 19757620
TI  - Acetaminophen as a postsurgical analgesic in rats: a practical solution to
      neophobia.
AB  - Acetaminophen administration is gaining popularity as a postsurgical analgesic in
      many rodent labs despite reports that animals may consume suboptimal doses as a
      result of taste neophobia. The present study evaluated the presence, duration,
      and extent of acetaminophen neophobia in adult male and female rats (Long Evans)
      with the intent of developing a protocol for administration of this analgesic in
      the rodent surgery lab. After a 7-day baseline period in which average water
      consumption, food consumption, and body weight were established for 32 rats (20
      females and 12 males), cherry-flavored acetaminophen was administered (6 mg/ml)
      in the animals' water bottles for an additional 7 days. Fluid consumption, food
      consumption, and weight were monitored during this period of drug exposure. Male
      rats displayed a transient period (1 day) of reduced fluid consumption followed
      by elevated fluid consumption on subsequent days. Female animals displayed normal
      to elevated fluid consumption on all days of drug exposure. Both male and female
      animals, however, decreased their food intake after drug exposure and
      subsequently lost weight. Recommendations for the oral administration of
      acetaminophen as a postsurgical analgesic are discussed.

PMID- 19757621
TI  - An outbreak of Pasteurella pneumotropica in genetically modified mice: treatment
      and elimination.
AB  - A closed breeding colony comprising genetically engineered, wild-type, and stock
      mice presented with varying degrees of bilateral mucopurulent conjunctivitis and
      panophthalmitis. The one mouse with unilateral corneal ulceration, a knockout
      animal, was submitted for necropsy, and bacterial culture samples were obtained
      from the affected eye and uterus. In addition, ocular swabs from another 12
      clinically affected animals, consisting of knockout, transgenic, wild-type, and
      stock mice, were submitted for bacterial culture analysis. All samples revealed
      pure cultures of Pasteurella pneumotropica. At the time of the outbreak, there
      were approximately 600 mice in the affected colony, with the majority of clinical
      cases (58 of 79) involving knockout mice and the remainder (21 of 79) in the
      other strains. Treatment consisted of enrofloxacin in the drinking water at 85
      mg/kg daily for 14 days. Within 7 days of initiation of treatment, all existing
      clinical cases had resolved and no new clinical cases developed. Four weeks after
      completion of treatment, two groups of mice were submitted for multiple organ
      bacteriological analyses. One group of mice represented those animals which had
      complete resolution of clinical signs, and the second group of mice represented
      those individuals which had remained asymptomatic throughout the outbreak. All
      post treatment bacterial culture samples were negative for Pasteurella
      pneumotropica. By using the oral enrofloxacin suspension in the drinking water
      rather than the parenteral counterpart, concerns regarding the pharmacokinetics,
      specifically drug bioavailability via the oral route, problems with aqueous
      immiscibility and drug degradation within an aqueous medium were not potentially
      confounding variables. The clinical management, ease of administration, and
      efficacy of using an oral antibiotic formulation for the treatment and
      eradication of Pasteurella pneumotropica from a large mouse colony are presented
      in this paper.

PMID- 19757622
TI  - Validation study of social housing of canines in toxicology studies.
AB  - Optimal housing conditions for canines have evolved in light of changing research
      findings and animal welfare initiatives. Social housing of canines in toxicology
      studies was not considered standard housing in our facility. When the decision
      was made to explore social housing for toxicology studies in our facility, we
      noted a lack of published information. This study was performed to develop and
      validate social housing as an option for canines in toxicology studies. The
      potential impact to data gathered through toxicology studies in which the canines
      are socially housed is discussed.

PMID- 19757623
TI  - A combined and comparative study of physiologic and behavioral parameters in a
      systemic toxicity test.
AB  - A knowledge of the acute systemic effects of materials that come into contact
      with body tissues and fluids is necessary to assess their clinical safety. Here
      we describe the use of bioradiotelemetry to record the heart rate, body
      temperature, and motor activity of freely behaving rats in conjunction with
      weight gain, food, and water consumption after administration of the bacterial
      endotoxin lipopolysaccharide and the heavy metal nickel chloride. The results of
      our study reveal that body temperature change was the more sensitive index of the
      two physiological parameters tested. Core body temperature can be monitored
      diurnally or nocturnally depending on whether a hyper- or hypothermic response,
      respectively, to the test solution is anticipated. Weight gain was the most
      sensitive index of all parameters monitored, but its use as an index requires
      that the test substance be administered nocturnally. Monitoring physiological
      parameters offers a complementary assessment of a systemic response, but these
      markers are not superior to conventional indices such as reduced weight gain. The
      use of two diverse toxic substances in the present study illustrates that test
      conditions are dictated by the nature of the systemic response induced by the
      substance tested.

PMID- 19757624
TI  - Quantification of TNF-alpha and IL-6 bioactivity in response to
      lipopolysaccharide in the degu (Octodon degus).
AB  - The proinflammatory cytokines TNF-alpha and IL-6 are important inflammatory
      mediators that may be regulated by circadian rhythms. However, the production and
      detection of these cytokines have not been examined in the degu, a diurnal
      species used in some studies of circadian rhythms. In this study, we used
      bioassays to attempt to measure tumor necrosis factor (TNF-alpha) and interleukin
      6 (IL-6) levels in degus exposed to an inflammatory stimulus, lipopolysaccharide
      (LPS). In an in vitro study, whole blood was incubated with LPS. After 6 and 24 h
      of LPS stimulation, TNF-alpha levels were substantially increased. However, IL-6
      was not found in any of the samples. In an in vivo study, LPS was given to degus
      intraperitoneally. Similar to responses seen in other species, LPS stimulation
      resulted in marked neutrophil recruitment into the peritoneal space but not the
      alveolar space. TNF-alpha was present in large amounts in plasma and/or
      peritoneal lavage fluid. Again, IL-6 was not detectable with the bioassay. These
      findings suggest that degus do not produce IL-6, that they produce IL-6 in
      extremely small amounts, or that the bioassay is unable to detect IL-6 from
      degus. In conclusion, using well-established models of acute inflammation, this
      study demonstrated that TNF-alpha, but not IL-6, could be detected in plasma and
      peritoneal lavage fluids from degus with standard bioassays used for cytokine
      detection in other species.

PMID- 19757625
TI  - Polycystic and chronic kidney disease in a young degu (Octodon degus).
AB  - A young adult (approximately 20 months), 125 g, female degu (Octodon degus) was
      housed with a male degu for approximately 1.2 years as a breeding pair. The
      female was multiparous and had weaned its third litter 2 weeks earlier. The degu
      was reported to the veterinary service for bloody vaginal discharge and a
      hunched, thin appearance of 1 day's duration. On physical examination, it
      exhibited cachexia, molting, slight matting of the hair around the eyes, and
      moderate dehydration. Hematology results included anemia and leukopenia with
      lymphocytopenia. Biochemical abnormalities included severe azotemia and
      phosphatemia. Urine specific gravity was 1.016. The condition of this animal
      prohibited its continued use in the breeding colony, so it was submitted for
      necropsy. On gross examination, the left kidney measured 10 x 15 mm, had an
      irregular surface, and was pale and mildly enlarged, consistent with compensatory
      hypertrophy. The right kidney was small (5 x 8 mm) and cystic. Both adrenal
      glands appeared mildly enlarged. Histologically, the left kidney had multiple
      regions with chronic, diffuse interstitial nephritis, and the right kidney was
      polycystic. There was mild, focal, cortical nodular hyperplasia in the adrenal
      glands. In the uterus, there was unilateral, locally extensive necrosis of the
      endometrium. The clinical chemistry results and histopathology findings are
      supportive of a diagnosis of renal failure secondary to chronic nephritis and
      polycystic kidney disease. The etiology of the nephritis is unknown. Polycystic
      kidney disease can be congenital or hereditary in other rodents.

PMID- 19757626
TI  - Shelter enrichment for rats.
AB  - Nest boxes are a simple and effective form of environmental enrichment. Rats
      accept a wide range of nest-box types but have the strongest relative T-maze
      preference for enclosed, opaque, thermoplastic boxes. All laboratories should
      provide their rats some type of nest box, depending on the most convenient and
      effective method.

PMID- 19757627
TI  - The Morris water maze.

PMID- 19757628
TI  - Management tools for success.

PMID- 19757629
TI  - The Animal Welfare Act, USDA, & research.
AB  - In the above discussion, the concept and evolution of IACUC oversight of research
      facility animal care and use programs and common USDA citations concerning these
      programs was reviewed. The majority of USDA citations are program-related and
      involve both IACUC and veterinary care functions. Common IACUC-related citations
      concern inadequacies involving required information in protocols (such as
      rationales for the species and numbers used and descriptions of the procedures
      proposed), searches for alternatives to painful or distressful procedures, and
      minimization of pain and distress. Common veterinary care citations concern
      inadequacies involving veterinary care facilities, daily observation of the
      animals, and veterinary care itself (e.g., maintaining inadequate records or
      using expired medications). IACUC's are advised to ensure that their program
      records are comprehensive enough to demonstrate that their facility's animal care
      and use program complies with the AWA and USDA regulations. The overall ongoing
      success of self-regulation in the research industry is acknowledged, and APHIS's
      current concentration on the recognition and alleviation of distress, as well as
      pain, is noted. In the future, APHIS will continue in its oversight role as IACUC
      programs continue to evolve in their awareness and application of the advances in
      pain and distress recognition and management. Together, we will continue to work
      for the benefit of the animals used in research, whose welfare is so important to
      the quality of that very research.

PMID- 19757630
TI  - The 3 R's for laboratory animal zoonoses.

PMID- 19757631
TI  - Reflections on the IACUC process.

PMID- 19757632
TI  - Crisis management--from a facilities-design perspective.

PMID- 19757633
TI  - Post-traumatic atrophy of the olfactory tract: clinicopathological features.
AB  - We present the clinicopathological features of a 51-year-old male patient with
      post-traumatic atrophy of the olfactory bulb and tract, and additional contusion
      on the base of the temporal lobe. Prior to death, there was no clinical evidence
      of an impaired olfactory function; the lesions were identified during post-mortem
      evaluation. Macroscopically, the left olfactory tract appeared to be
      substantially diminished in volume, whereas the right olfactory tract could not
      be identified within the markedly fibrotic leptomeninges in the fronto-orbital
      region. Postmortem MRI examination of the brain demonstrated superficial defects
      in the fronto-orbital cortex on the right side, corresponding to the region of
      the atrophic olfactory tract. Microscopic examination revealed degenerative
      changes with reactive gliosis and a large amount of corpora amylacea most
      pronounced in the right olfactory tract. The pathophysiologic mechanisms of
      olfactory degeneration after head trauma are discussed.

PMID- 19757634
TI  - Splenic hemangiomatosis. A report of two cases and review of literature.
AB  - Splenic vascular tumors represent a wide spectrum of lesions, ranging from benign
      to highly aggressive neoplasms. Among benign tumors, localized hemangiomas are
      the most frequent. Splenic hemangiomatosis is currently considered a diffuse
      variant of hemangioma, characterized by total or subtotal replacement of the
      splenic parenchyma by a vascular proliferation featuring the usual morphological
      findings of hemangioma. To the best of our knowledge based on a review of the
      medical literature, less than twenty cases have been described. Moreover,
      pediatric cases are absolutely exceptional. We report two new cases of splenic
      hemangiomatosis respectively occurring in a 1-year-old child and in a 30-year-old
      woman, with particular attention to the histological and immunohistochemical
      findings; related problems of differential diagnosis are also discussed.

PMID- 19757635
TI  - Central nervous system microangioarchitecture in the human foetus.
AB  - It is thought that arterioles penetrating the central nervous system behave as
      terminal arteries and lack for anastomosys. The purpose of our study was to
      define the angiogenesys in the fetal encephalon at different stages of
      development. To this purpose, we examinated 13 fetal and newborn encephalons
      between the 10th and 33rd week. To label blood vessels, we used an
      immunohistochemical procedure based on the detection of two antigens located
      within endothelial cells: CD31 and CD34. The cerebral vascularization modifies in
      quantity and in structure during pregnancy, with important topographic
      differences between cerebral cortex and striatal-limbic areas. We observed two
      microarchitectural patterns: 1. Rectangular mesh pattern, characterized by
      capillaries that join transversally to one or more branches that deepen
      orthogonally from the surface of the meninges; 2. Hexagonal mesh pattern, which
      surrounds small groups of neurons and develops with a honeycomb shape. The
      rectangular mesh pattern is mostly observed from the 13th to 26th week in the
      white matter, in the hippocampus and in the cortex. The hexagonal mesh pattern is
      typical of the basal nuclei, and of the cerebral cortex during the 10th-12th week
      and after the 26th-27th week. Until the 26th week the vascularization increases
      mainly in the hippocampus and in the basal nuclei. The cortex shows a
      vascularization increment, greater than in the limbic system, with a pattern
      prevalently hexagonal in areas were the neurons' number increases. Our data
      demonstrate that, in the human fetus, cerebral capillaries are not of terminal
      type. On the contrary, they show a rich anastomotic network that has different
      patterns in white matter (rectangular pattern) or in grey matter (hexagonal
      pattern). The functional meaning of this difference is unknown, but we can
      suppose that its role is to warrant availability of nutritional substances within
      regions where a high number of neurons is present. Recent findings in
      computational neuroanatomy show that computer simulated axonall symmetric
      bifurcation can generate a dendritic tree with close similarities with real
      observed vascular patterns in fetal cortex.

PMID- 19757636
TI  - Sclerosing haemangioma with a predominant sclerotic pattern: an unusual pulmonary
      lesion which can be misdiagnosed.
AB  - AIMS: An unusual sclerosing haemangioma of the lung with a predominant sclerotic
      pattern is described. MAIN RESULTS AND CONCLUSIONS: The patient was a 51-year-old
      male, presenting with a well-circumscribed nodule, 0,6 cm in diameter, located in
      the lower lobe of the left lung. He is alive and well 9 years after surgical
      excision of the nodule. Microscopically, the lesion was well demarcated and
      mostly composed of sclerotic tissue, with numerous irregular entrapped alveolar
      spaces The characteristic bland, round cells with abundant pale cytoplasm,
      immunohistochemically positive for TTF-1 and negative for cytokeratin, were
      limited to small clusters embedded in the stroma at the periphery of the nodule.
      The most important differential diagnostic considerations of the sclerotic
      variant of pulmonary sclerosing haemangioma are briefly discussed.

PMID- 19757637
TI  - True prostatic blue nevus associated with melanosis: case report, histogenesis
      and review of the literature.
AB  - We describe a case of true blue nevus of the prostate associated with prostatic
      melanosis, occurring in a 66-year-old man, who underwent multiple echo-guided
      prostatic fine-needle biopsies for a suspect prostatic adenocarcinoma. The
      histological features observed in the bioptic samples were chronic and acute
      inflammation, together with the presence of polygonal or elongated dendritic
      elements, scattered within the fibromuscular stroma and containing in their
      cytoplasm a brown pigment, staining black with the Fontana Masson stain, negative
      for the Perls stain, bleaching with potassium permanganate treatment and
      imunoreactive for S-100 protein. The presence of melanin pigment in the prostate
      is an extremely rare occurence, which may be due to melanosis, blue nevus and
      malignant melanoma, the latter showing distinctive cytological atypia. The
      recognition of each entity is fundamental for clinical and prognostic
      implications.

PMID- 19757638
TI  - Clinical coding supplement. Issue 2: The bladder.

PMID- 19757639
TI  - Caldicott and healthcare information governance, from an acute trust's
      information governance manager's perspective.

PMID- 19757640
TI  - Successful salvage and restoration of damaged records after fire and flood.

PMID- 19757641
TI  - Blame Canada!

PMID- 19757642
TI  - There from here ... and home again.

PMID- 19757643
TI  - Sitting in someone else's chair: dentistry in Norway.

PMID- 19757644
TI  - Tax Act encourages business purchases in 2009.
AB  - In talking with dentists, the awareness level of the opportunity provided by the
      American Recovery and Reinvestment Act seems to be rather low. The Act provides
      tax breaks for dental practice owners to create jobs by making it attractive to
      invest in their practices. However, lower taxes should not be what drives the
      decision making process. First and foremost, the capital improvements need to
      make sense from a business and return-on-investment standpoint. There is not much
      time to complete the project(s) in 2009 and to benefit from the tax breaks
      afforded by the ARRA. Therefore, dentists should consult with their tax advisors
      as soon as possible to take full advantage of the provisions the Act provides.

PMID- 19757645
TI  - Horizons: the 2009 Table Clinics.

PMID- 19757646
TI  - RM matters: war of words.

PMID- 19757647
TI  - What's a dentist to do? The horses are out of the barn.

PMID- 19757648
TI  - Cross-training makes for a better dental team ... and a better dentist.

PMID- 19757650
TI  - "It's nice to be just one of the guys ... even though I'm not".

PMID- 19757649
TI  - Payor report card.

PMID- 19757651
TI  - Maximizing access to health care in New Jersey the case for advanced practice
      nurses: a White Paper.

PMID- 19757652
TI  - The demographics of this country are changing rapidly.

PMID- 19757653
TI  - Health literacy.

PMID- 19757654
TI  - [Changing paradigms in the diagnosis (primary and of recurrences) and the
      treatment of urothelial cancer: preparing the future].

PMID- 19757655
TI  - [Editorial comment on the analysis of bottled and tap water in Spain and the
      impact of its consumption on urinary lithiasis].

PMID- 19757656
TI  - [Editorial comment on how body mass index and diet affect the development of
      prostatic cancer].

PMID- 19757657
TI  - [The Open Access Initiative (OAI) in the scientific literature].
AB  - According to the declaration of the Budapest Open Access Initiative (OAI) is
      defined as a editorial model in which access to scientific journal literature and
      his use are free. Free flow of information allowed by Internet has been the basis
      of this initiative. The Bethesda and the Berlin declarations, supported by some
      international agencies, proposes to require researchers to deposit copies of all
      articles published in a self-archive or an Open Access repository, and encourage
      researchers to publish their research papers in journals Open Access. This paper
      reviews the keys of the OAI, with their strengths and controversial aspects; and
      it discusses the position of databases, search engines and repositories of
      biomedical information, as well as the attitude of the scientists, publishers and
      journals. So far the journal Actas Urologicas Espanolas (Act Urol Esp) offer
      their contents on Open Access as On Line in Spanish and English.

PMID- 19757658
TI  - [Body mass index and diet affect prostate cancer development].
AB  - INTRODUCTION: Prostate cancer (CaP) is one of the most important causes of
      morbidity and mortality in the world. There is evidence that obesity and
      inadequate eating habits may promote CaP development. OBJECTIVE: To analyze and
      compare the body mass index (BMI) and the food intake, especially fats and
      antioxidants, among subjects with CaP and those free of disease as a control
      group. MATERIAL AND METHODS: A sample of 40 men between 50 and 80 years old were
      selected for the study: 20 with CaP and 20 healthy men as control group. All
      volunteers underwent a digital rectal examination, prostate specific antigen
      level, ultrasound and transrectal prostate biopsy, and a nutritional interview
      where a dietary history and different anthropometric measurements were made.
      Statistical analysis was performed using the Student T test for independent
      samples (p < 0.05). RESULTS: BMI in the subjects with CaP was higher than in
      controls (29.8 kg/m2 vs. 27.96 kg/m2, p = 0.13) but not statistically
      significant. However, there was a direct correlation between BMI and tumor
      aggressiveness (r = 0.79, P < 0.001). Total, saturated, monounsaturated and
      polyunsaturated fat intake was significantly higher in subjects with CaP; while
      omega3 fatty acids, vitamin C and lycopene intake was significantly lower than in
      controls (p < 0.05). CONCLUSIONS: A healthy weight and a diet low in total fat,
      saturated, monounsaturated and polyunsaturated fat and rich in n3 fatty acids,
      vitamin C and lycopene is associated with a lower risk of CaP.

PMID- 19757659
TI  - [Prolonged hypogonadism after cessation of androgen deprivation therapy for
      prostate cancer].
AB  - OBJECTIVES: To study the levels of LH, testosterone and PSA after suspending
      prolonged treatment with LH-RH analogs. MATERIALS AND METHOD: Hormonal evolution
      was studied in 29 patients from whom treatment had been withdrawn. The patients
      had previously been receiving treatment with LH-RH analog for more than one year,
      and with LH< 2 mUI/mL and testosterone < 2.8 ng/mL. LH, testosterone and PSA were
      determined monthly, together with clinical assessment. The treatment was re
      initiated and the period of monitoring ended before the presence of clinical
      progression and/or PSA > or = 10 ng/mL. The cohort was described and survival was
      calculated using Kaplan-Meier and Cox regression. RESULTS: The mean period of
      time without treatment for the series was 35 months (CI 95%, 15.7-54.2 months).
      Prolonged hypogonadism (> 24 months) was presented by 17% of the patients. The
      recovery of the LH-T-PSA axis, when it occurred, followed the expected sequence.
      The variables that influenced the period of recovery of the PSA were the PSA
      pretreatment and the association of an antiandrogen. CONCLUSIONS: After
      withdrawing the prolonged treatment with LH-RH analogs, most of the patients
      recovered the levels of LH-T-PSA, although a subgroup remained hypogonadic for
      more than 24 months.

PMID- 19757660
TI  - [Laparoscopic radical nephrectomy in big surgical specimens].
AB  - INTRODUCTION: The retroperitoneal surgery is the clearer indication for the
      laparoscopic approach. Still there are indications for open surgery because of
      the complexity of the patient and the surgeon experience. OBJECTIVES: The main
      objective is to report our experience of laparoscopic radical nephrectomies in
      patient with tumors greater than 7 cm. or surgical specimens with more than 700 g
      of weight. We analyze their characteristics, complications rate, surgical time,
      postoperative outcome and hospital stay. MATERIALS AND METHODS: Since July 2004
      to July 2008 we have performed 104 laparoscopic radical nephrectomies. We have
      selected 41 patients with characteristics of big surgical specimens. RESULTS: The
      average surgical time has been of 184,3 min. Only 1 case has been converted into
      open surgery and only 1 intraoperative death because of cardiologic arrhythmia.
      The average hospital stay has been of 3,51 days. The complications rate and
      postoperative outcome are similar to the whole series. DISCUSSION: Laparoscopic
      nephrectomy is technically less complex than radical prostatectomy. However,
      their possible complication implies a much bigger severity. The more complex
      cases must be approach laparoscopically only after a wide experience. Actually,
      in our department we usually indicate an open approach when surgical specimen
      crossover the abdominal middle line and in those cases where the tumoral thrombus
      affect the main renal vein and/or the vena cava.

PMID- 19757661
TI  - [Robotic radical cystoprostatectomy: oncological and functional analysis].
AB  - INTRODUCTION: The da Vinci robotic laparoscopic surgery, has been shown in
      radical prostatectomy, optimal functional and oncological results with a lower
      learning curve, greater comfort and vision for the surgeon, and proper
      preservation of the neurovascular bundles. This has led to begin the experience
      with robotic radical cystectomy (RRC). OBJECTIVES: Review our initial experience
      in CRR, evaluating surgical and functional results obtained, and also immediate
      and short-term complications. MATERIAL AND METHODS: Between December 2007 and
      January 2009 we performed nine robotic radical cystoprostatectomy and in seven
      patients robotic lymphadenectomy (LDN). Five patients had a muscle-invasive
      disease and 4 non-muscle invasive bladder cancer. The median age was 57 years
      (range 34-81). Urinary diversion was performed extracorporeally in all cases, 3
      cases an ileal conduit and 6 an Studer neobladder in 3 of these 6 cases, the
      urethra-neobladder anastomosis was performed intracorporeally. RESULTS: The
      average time of surgery was 300 minutes (range 280-420) in the ileal conduit and
      360 (range 330-540) in the Studer. No cases required conversion or blood
      transfusion. The median number of nodes removed by LDN robotics was 10 (range 6
      18). The pathology revealed 3 pT0. 2 CIS, 3 pT3, 1 pT4b (positive margins). With
      a median follow up of 7 months there have been no peritoneal implant and only one
      ureteral stenosis. Oral diet was initiated in 5 cases at 48 hours. Of the 6
      patients with preserved sexual function preoperatively and followup of more than
      3 months, 2 had full erection at 1 month, 2 at 3 and 6 months, and the remaining
      2 presented with a full erection with 5 PD inhibitors at 3 and 9 months. All
      patients with neobladder presented correct daytime continence. The average
      hospital stay was 8.5 days (range 7-19). CONCLUSIONS: The radical robotic
      cystectomy with extracorporeal reconstruction of the urinary diversion offers
      good early functional and surgical outcomes. The careful preservation of the
      neurovascular bundles in radical pelvic surgery provides excellent results in
      urinary and sexual function.

PMID- 19757662
TI  - [Laparoscopic simple nephrectomy with transvaginal notes assistance and the use
      of standard laparoscopic instruments].
AB  - INTRODUCTION: Natural orifice transluminal endoscopic surgery (NOTES) is an
      emerging technique, which allows to performed surgical procedures avoiding any
      surgical scars. However there are some problems due to the lack of equipment
      available for these procedures. The aim of these study is to present our initial
      experience with the transvaginal nephrectomy NOTES using standard laparoscopic
      instruments. MATERIAL AND METHODS: Two female patients 23 and 29 years old, both
      of them with diagnosis of recurrent urinary tract infection and renal atrophy. A
      transvaginal simple nephrectomy was performed using a transvaginal Access for the
      camera port and two abdominal work ports of 10 and 3 mm. RESULTS: Total operation
      room time was 120 min in the first case and 40 min. in the second with an average
      blood loss of 200 cc. There were no perioperative complications, and both
      patients was discharged 36 hours after the surgery CONCLUSION: Laparoscopic
      nephrectomy with transvaginal NOTES assistance is technically feasible with the
      use of standard laparoscopic instruments. Special Access trocars and instruments
      development for this procedure will allow to perform a pure technique without the
      use of abdominal incisions.

PMID- 19757663
TI  - [Photoselective vaporization of the prostate with Laser Greenlight HPS: current
      role, technical aspects and review of the literature].
AB  - Photoselective vaporization of the prostate with 120W HPS Greenlight laser is one
      of the most attractive modalities of surgical treatment for benign prostatic
      hyperplasia at present. The specific physical characteristics of this laser
      provides an excellent safety and effectiveness profile, making it the ideal
      technique for high-risk patients or patients ongoing oral anticoagulation.
      Moreover, the undeniable reduction of urethral catheterization time and hospital
      stay compared to transurethral resection of prostate (TURP) involves a much more
      comfortable postoperative period for patients. We have conducted a Medline/Pubmed
      search, presenting in this review the outcomes and current surgical techniques
      described in recent studies. We have also reviewed the controversial aspects and
      limitations attributed to this technique.

PMID- 19757664
TI  - [Spanish bottled and tap water analysis and their relation with urinary
      lithiasis].
AB  - OBJECTIVE: To perform a chemical analysis of all the available waters in Spain
      with the idea of offering consume recommendations to lithiasic patients. MATERIAL
      AND METHODS: Information research of the chemical composition of Spanish tap and
      bottled water in publications, supermarkets and Internet. A descriptive study,
      and a correlation study between water components by means of Pearson test were
      performed. RESULTS: Information about composition from tap water of most of the
      main Spanish cities and 85 bottled water brands was found. A significant
      correlation between calcium and magnesium concentration (p = 0.0001) and high
      correlation between bicarbonate and sodium concentration (p = 0.0001, Pearson
      coefficient 0.958) was found. It is also offered water classifications according
      to calcium, bicarbonate, sodium and magnesium concentrations. CONCLUSION: A
      guideline about water election for lithiasic patients is offered according to
      their geographical origin and dietetic preferences, mainly lactic consume.

PMID- 19757665
TI  - [Female urethral stricture: etiology, diagnostic and treatment].
AB  - Female urethral stricture is an infrequent cause of bladder outlet obstruction,
      which is also a rare clinical entity in women. The most frequent etiology is the
      previous urogenital surgery. Periurethral fibrosis is the final cause regardless
      the etiology. Considerably controversie surrounds in the diagnostic criteria but
      the estrictures are structural obstructions which involve media and distal third
      of the female urethra. There is no treatment consensus, but less agresive
      maneuvers such as dilatations and urethrotomies are chosen to treat primary
      estrictures, although the high recurrence rates. Reconstructive tecniques with
      the use of several flaps and grafts should be considered in recurrent cases and
      when there is a partial or total urethral defect.

PMID- 19757666
TI  - [Coital urinary incontinence. Associated symptoms and severity of incontinence].
AB  - INTRODUCTION: The objective of present study was to analyze the relationship
      between coital urinary incontinence (UI) and the symptoms of Stress UI (SUI),
      Urge UI (UUI) and the extent to which they impair the patient's life, measured
      through the ICIQ-UI SF questionnaire in a sample of sexually active women with UI
      symptoms. METHODS: Epidemiologic, observational, cross-sectional and multicentric
      study of 1,735 women with diagnostic of urinary incontinence (UI). Patients who
      were not sexually active were excluded, remaining 1,292 patients for the
      analysis. All women filled in the ICIQ-UI SF questionnaire and the King's Health
      Questionnaire (KHQ). RESULTS: According to KHQ, the prevalence of coital
      incontinence was 29.4%. Women with coital incontinence compared to those who did
      not suffer from it, had similar mean age and body mass index, were more likely to
      have symptoms of SUI (37.6% vs. 27.7%) and less likely to have UUI (16.6% vs.
      27.4%) (p < 0.001). 36.1% of women with SUI had coital UI; this percentage was
      lower for women with UUI (20.1%). ICIQ-UI global score was higher in women with
      coital incontinence, 14.1 vs. 12.1 (p < 0.001), difference that was mainly due to
      the dimension "affectation" rather than "frequency" and "amount" dimension
      scores. DISCUSSION: Coital IU seem to be associated to SUI and to a higher
      severity of the urinary incontinence measured by the ICIQ-UI SF. Probably this
      association is due to the fact that ICIQ-UI-SF includes in its score the impact
      of patients' UI symptoms on their life and coital incontinence has an important
      effect on the quality of life of sexually active women.

PMID- 19757667
TI  - [Risk factors for bladder injuries during cesarean section].
AB  - OBJECTIVE: To identify risk factors for bladder injury during cesarean delivery,
      to let patients and doctors know them and their importance. METHODS: We conducted
      a case-control study of women undergoing cesarean delivery at the Instituto
      Nacional de PerinatologiaIsidro Espinosa de los Reyes between January 2001 and
      December 2007. Cases were women with bladder injuries at the time of cesarean
      section. Two controls per case were selected randomly. Medical records were
      reviewed for clinical and demographic data to compare them. RESULTS: Twenty-one
      bladder injuries were identified among 24, 057 cesarean sections, (incidence
      0.087%), only 19 were analized. Prior cesarean section was more prevalent among
      cases than controls (63% vs 42% p 0.134), with an OR of 2.35 (95% CI 0.759
      7.319), when we take only patients with one cesarea in contrast with no cesarea
      the OR is 3.75 (95% CI 1.002- 14.07). Statistically significant differences (P
      values < .05) between cases and controls were found in gestacional age (38.16 vs
      37.35 weeks), prior cesareans (42% vs 18%), adhesions (79% vs 5%), Odds ratio of
      67.5 (95% CI 11.14- 408), VBAC (31.5 vs 3%), median skin incision (16% vs 68%),
      Pfannenstiel (84% vs 32%), blood loss (744cc vs 509cc) and length of surgery 135
      vs 58 minutes). No differences were found among age, BMI, prior surgery, labor,
      premature rupture of membranes, station, chorioamnioitis, induction, uterine
      incision, timing of delivery, uterine rupture. CONCLUSION: Prior cesarean section
      and adhesions are risk factors for bladder injury at the time of repeat cesarean
      delivery. Elective cesarean delivery is valid but it is duty of physicians to
      inform patients the risks of it.

PMID- 19757668
TI  - [Liposarcoma of the espermatic cord: our experience and review of the
      literature].
AB  - INTRODUCTION: The paratesticular tumors represent 7-10% of the intraescrotales
      masses. Sarcomas includes 90% of the espermatic cord malignant lessons and
      approximately the 3-7% are liposarcomas. MATERIAL AND METHODS: We presented our
      experience with two cases of paratesticular liposarcomas. RESULTS: Actually it
      has been reported near 161 cases of paratesticular liposarcoma. Due to the rarely
      of this pathology it is difficult to know its natural history and to reach
      conclusions of the treatment results, which one until the moment continues being
      radical orchiectomy with wide local resection of the surrounding soft tissues,
      the value of adjuvant radiation and chemotherapy is even controversial.
      CONCLUSIONS: Sarcomas of the espermatic cord are rare, their initial treatment is
      surgical, we recommended the transoperatory valuation of the surgical edges to
      try to diminish the recurrence frequency.

PMID- 19757669
TI  - [Bladder leiomiosarcoma. A new case and a review of the literatura].
AB  - Bladder Leiomiosarcomas are exceptional mesenchimal tumours. Their differential
      diagnosis is basic to decide our therapeutic attitude. We present a new case of
      bladder leiomiosarcoma with a bad behavior and with multiple relapses, and
      perform a review of the literature in order to establish more properly the
      therapeutic attitudes.

PMID- 19757670
TI  - [Pulmonary fibrosis and endovesical mitomycin C].
AB  - The Mitomycin C is a chemotherapeutic agent used in several types of carcinomas.
      In the superficial vesical carcinoma comes using since more than a quarter
      century in the form of endovesical instillations. It is a drug relatively safe,
      although there have been described adverse effects related to its systemic
      administration as myelosuppression, anaemia, kidney toxicity and less frequently
      pulmonary fibrosis. In this article we presented the case of a patient who
      suffers a respiratory illness compatible with interstitial lung disease that
      develops a respiratory severe insufficiency finishing with the death, after the
      administration of endovesical mitomycin C, being this adverse effect exceptional
      for this route of administration.

PMID- 19757671
TI  - [Primary lymphoma of penis].
AB  - We describe a case of primary penis lymphoma in a 71 yr old man. We review the
      bibliography and we emphasize the peculiarity and different sorts of clinical
      presentation. The initial symptoms were insidious. Physical examination and
      ultrasound findings made it indistinguishable from other tumors. A MRI confirmed
      the presence of a tumoral process with a homogeneous density in the distal part
      of the penis whose biopsy with immune histological processing confirmed us the
      diagnosis of primary penis lymphoma. The combined treatment with chemotherapy and
      radiotherapy allowed preserving the sexual organ and being without disease at 48
      month of follow up.

PMID- 19757672
TI  - [Stab wounds of the kidney: conservative management. Two new cases and review of
      the literature].
AB  - INTRODUCTION: Stab wounds of the kidney have traditionally been managed by open
      surgery. Nowadays the conservative management of stab wounds injuries is extended
      in order to avoid unnecessaries nephrectomies and laparotomies without increasing
      morbidity and mortality. Although there is no a strong evidence to recommend when
      to operate or what sort of follow up we must do. MATERIAL AND METHODS: We present
      two new cases of stab wounds injuries managed conservatively. We performed a
      systematic review of the literature. RESULTS: Both patients evolved favorably
      although one of them presented hematuria 7 days after the traumatism and we
      performed an embolization of an arteriovenous fistula. Most of the articles are
      based on series of cases or retrosprospective studies. CONCLUSIONS: The diagnosis
      and staging of stab wounds of the kidney must be done with clinic and CT scan.
      Conservative management is required when the patient is not hemodinamically
      unstable and injuries do not require inmediate repair. These patients require a
      long-term follow up to prevent the appearance of complications. Randomized
      prospective multicenter trials are needed to support the optimum management for
      each kidney injury degree.

PMID- 19757673
TI  - [Renal cyst infected by Brucella].
AB  - OBJECTIVES: To report one case of renal cyst infected by Brucella, an exceptional
      pathology in our environment. METHODS: 82-year-old patient who was referred from
      his primary care physician for persistent microhematuria and piuria without
      evidence of infection. RESULTS: Radiological studies (XR+US+CTscan) showed a left
      renal cyst with parietal calcifications. Pathologic study was compatible with
      complicated cyst, with cultured (+) to Brucella spp. CONCLUSIONS: Renal
      involvement by Brucella is exceptional, and the cystic renal involvement is by
      far one of the more exceptional manifestations.

PMID- 19757674
TI  - [Urethral and bladder perforation by TOT urethropexy mesh].

PMID- 19757675
TI  - [Intestinal subocclusion after laparoscopy].

PMID- 19757676
TI  - [Penile incarceration with metallic ring].

PMID- 19757677
TI  - [Synchronous bilateral seminoma].

PMID- 19757678
TI  - Comparison of the oxidative status of vitamin E-supplemented and non-supplemented
      cows under field conditions.
AB  - The effect of oral vitamin E supplementation during the dry period on serum
      biomarkers of oxidative status was evaluated in an observational field study.
      Ninety-eight cows were selected from 26 herds in the Netherlands. On 15 farms dry
      cows were supplemented with a dry-cow mineral mix containing 1000 IU vitamin E
      (vitamin E+ group, n = 52), and on 11 other farms dry cows did not receive the
      supplement (control group, n = 48). A blood sample was taken from all cows
      between 0 and 28 days before calving. Serum levels of alpha-tocopherol,
      cholesterol, triacylglycerol, superoxide dismutase (SOD), glutathione peroxidase
      (GSHpx), uric acid, albumin, protein sulphydryl oxidation level, reactive oxygen
      metabolites (ROM), iron, the ferric reducing ability (FRAP), and malondialdehyde
      (MDA) were measured. Alpha-tocopherol levels were significantly higher in the
      vitamin E+ group, as was the alpha-tocopherol:cholesterol ratio. MDA levels were
      significantly lower in the vitamin E+ group, suggesting that levels of lipid
      peroxidation were lower with vitamin E supplementation. In conclusion, vitamin E
      supplementation increases alpha-tocopherol and lowers MDA serum levels.

PMID- 19757679
TI  - [Serious lungworm infection in dairy cows].

PMID- 19757680
TI  - [Instruments, books and other objects memorable to (almost) forgotten opinions,
      therapies, buildings, etc. What walks there?].

PMID- 19757681
TI  - [On the leash].

PMID- 19757682
TI  - [Birds and special animals in Europe under one umbrella?].

PMID- 19757683
TI  - [Oostvaardersplassen].

PMID- 19757684
TI  - [Veterinary Central Information System (Vetcis) has started].

PMID- 19757685
TI  - ['It does not only concern the testing of the rules, but also the effect'].

PMID- 19757686
TI  - ['Opting-out'].

PMID- 19757687
TI  - [European symposium about parasitic and arthropod transmitted diseases].

PMID- 19757688
TI  - [Multidisciplinary way to improve the welfare of farm animals].

PMID- 19757689
TI  - [European mastitis panel].

PMID- 19757690
TI  - The modern management of splenic injury: a model for coordinated trauma services.

PMID- 19757691
TI  - Study on the frequency of hepatitis B and C infection in chronic psychiatric
      patients in Hamedan in 2006-2007.
AB  - OBJECTIVE: To study on the frequency of hepatitis B and C infections in chronic
      psychiatric patients in Day Night Patient Care Centres in Hamedan in 2006-2007.
      METHODS: This is a cross sectional study done on 170 patients with chronic mental
      disorders admitted in patient care institutions of Hamedan in 2006-2007. Positive
      tests for HCV-Ab were confirmed by RIBBA test. RESULTS: Of 170 patients, 56% were
      males and 44% were females, (age range 15-71 years). Hepatitis B and C infection
      was found only in males, with Hepatitis B in 1.8% patients. All of Hepatitis B
      cases two thirds of Hepatitis C cases were institutionalized in one of the
      centers. CONCLUSIONS: Overall frequency of Hepatitis B and C infections in
      chronic psychiatric patients in care centers is more than the general population
      and centralization of these cases in one center causes transmission of infection
      if the standard precautions are not observed.

PMID- 19757692
TI  - CSF lactate level: a useful diagnostic tool to differentiate acute bacterial and
      viral meningitis.
AB  - OBJECTIVES: To evaluate the potential role of CSF lactate level in the diagnosis
      of acute bacterial meningitis and in the differentiation between viral and
      bacterial meningitis. METHODS: This was a hospital based observational study,
      conducted at Infectious Diseases Unit, Rashid Hospital Dubai, United Arab
      Emirates, from July 2004 to June 2007. The patients with clinical diagnosis of
      acute bacterial meningitis and who had CSF Gram stain/culture positive, CSF
      analysis suggestive of bacterial meningitis with negative Gram stain and culture
      but blood culture positive for bacteria and patients with clinical diagnosis
      suggestive of viral meningitis supported by CSF chemical analysis with negative
      Gram stain and culture as well as negative blood culture for bacteria were
      included in the study. CT scan brain was done for all patients before lumber
      puncture and CSF and blood samples were collected immediately after admission.
      CSF chemical analysis including lactate level was done on first spinal tap. The
      CSF lactate level was tested by Enzymatic Colorimetric method. RESULTS: A total
      95 adult patients of acute meningitis (53 bacterial and 42 viral) fulfilled the
      inclusion criteria. Among 53 bacterial meningitis patients, Neisseria
      meningitides were isolated in 29 (54.7%), Strept. Pneumoniae in 18 (33.96%),
      Staph. Aureus in 2 (3.77%), Klebsiell Pneumoniae in 2 (3.77%), Strept. Agalactiae
      in 1 (1.8%) and E. Coli in 1 (1.8%). All the patients with bacterial meningitis
      had CSF lactate > 3.8 mmol/l except one, whereas none of the patients with viral
      meningitis had lactate level > 3.8 mmol/l. The mean CSF lactate level in
      bacterial meningitis cases amounted to 16.51 +/- 6.14 mmol/l, whereas it was
      significantly lower in viral group 2.36 +/- 0.6 mmol/l, p < .0001. CONCLUSION:
      CSF lactate level was significantly high in bacterial than viral meningitis and
      it can provide pertinent, rapid and reliable diagnostic information. Furthermore,
      CSF lactate level can also differentiate bacterial meningitis from viral one in a
      quick and better way.

PMID- 19757693
TI  - Lipid profile in patients with psoriasis presenting at Liaquat University
      Hospital Hyderabad.
AB  - OBJECTIVE: To determine the lipid abnormalities in patients with psoriasis and
      compare it with healthy controls. METHODS: Across-sectional controlled study was
      conducted at the Department of Dermatology Liaquat University Hospital Hyderabad
      from January 2007 to November 2007. The study included 158 consecutive patients;
      among which 88 were males (44 patients and 44 controls) and 70 females (35
      patients and 35 controls). The patients with psoriasis having less than 30% body
      involvement were included in the study. Patients with severe psoriasis, high BMI
      (.30 kg/m2), hypertension, diabetes, smoking, alcohol consumption and personal or
      family history of hyperlipedemia were excluded. The patients were examined
      clinically and findings recorded on a pre-designed proforma. Fasting lipids were
      measured using SELECTRA XL chemistry analyzer using Spin react kits (made in
      Spain) by direct method. RESULTS: All patients had psoriasis involving less than
      30% of body surface. Their ages ranged from 18 years to 68 years (mean 37 +/-
      7.96 years). Family history of disease was positive in 10 (6.32%) patients. 134
      (84.8%) had plaque type psoriasis, 10 (6%) had in addition scalp and nail
      involvement, 05 (3.16%) guttate lesions, 05 (3.16%) had palmoplantar lesions
      while remaining 04 (2.43%) comprised of hyperkeratotic and flexural psoriasis.
      The duration of disease ranged between 18 months to 10 years with a mean of 4.5
      +/- 1.89 years. Serum cholesterol, triglycerides and low density lipoprotein
      (LDL) cholesterol were significantly higher than in the normal control group (P <
      0.01). There was no significant statistical difference in serum levels of very
      low density lipoprotein cholesterol (VLDL) and high density lipoprotein
      cholesterol (HDL-C) between the two groups. CONCLUSION: Psoriasis is an
      independent risk factor for hyperlipidaemia and its possible subsequent sequelae
      such as obstructive vascular disease.

PMID- 19757694
TI  - Predictors of lymph node involvement in bladder cancer treated with radical
      cystectomy.
AB  - OBJECTIVE: To identify the clinical variables associated with prevalence of lymph
      node metastasis in patients with bladder cancer treated by radical cystectomy and
      lymphadenectomy for primary bladder cancer. METHODS: Review of records of Ninety
      five patients who underwent radical cystectomy and pelvic lymph node (LN)
      dissection during the period of 1995-2008 from a prospectively maintained
      database. Eighteen patients were excluded due to lack of data on the nodal
      status, leaving 77 evaluable patients. Associations between LN metastasis and
      age, gender, duration of disease, number of transurethral resection (TUR) prior
      to cystectomy, pathological grade and tumour stage was analyzed. Data was
      analyzed using the SPSS software, version 15. Statistical tests applied were
      independent sample t test or the Mann Whitney U test, the chi-square test and the
      Fischer exact test. RESULTS: The median age of the patients was 58 years in lymph
      node negative group and 63 years in lymph node positive group. There were 87%
      males and 13% females. LN metastasis was detected in 19 (25%) patients. Mean
      duration of disease in LN negative patients was 537 +/- 997 days compared to 509
      +/- 708 days in LN positive patients. Mean number of TUR were same in both the
      groups, pathological grade was not found significantly different in both groups,
      where as primary tumour stage was found to be significantly (p < 0.05) higher in
      LN positive patients. CONCLUSIONS: Higher primary tumour stage at radical
      cystectomy is associated with higher prevalence of lymph node metastasis.

PMID- 19757695
TI  - Acute acalculous cholecystitis in dengue fever.
AB  - OBJECTIVE: To investigate the frequency, clinical features, management and
      outcome of acute acalculous cholecystitis in dengue fever patients. METHODS:
      Forty patients were admitted with the diagnosis of dengue fever, according to the
      clinical manifestations and laboratory investigations. The diagnosis of dengue
      fever was confirmed by a positive IgM antibody test result for a late or
      convalescent phase blood specimen. The diagnosis of acute acalculous
      cholecystitis was made according to clinical features and sonographic findings.
      Liver function tests, complete blood counts were determined. Abdominal ultrasound
      was performed with a real time scanner in patients with abdominal pain and
      abnormal results on liver function tests. RESULTS: Eleven out of 40 patients of
      dengue fever (27.5%) had complication of acute acalculous cholecystitis. There
      were 8 males and 3 females. The mean and standard deviation from the onset of
      fever to hospital visit was 3.3 +/- 0.8 days (range 2-5 days). The mean white
      cell counts was 4154 +/- 1577.5 cmm. The mean platelet counts were 26,727 +/-
      10460.3 cmm on presentation in hospital. The mean SGPT level was 148.5 +/- 190.17
      mg/dl. Mean alkaline phosphatase was 398 +/- 214.8 mg/dl. On sonography all had
      thickened gall bladder. The mean gall bladder wall thickness was 5.2 +/- 1.3 mm.
      Three patients had ascites and one patient had pleural effusion. CONCLUSION:
      Acute acalculous cholecystitis was seen in a significant proportion of patients
      with dengue fever. All patients improved with good hydration and correction of
      thrombocytopenia. Based on these observations it is suggested that close
      observation and initial treatment of thrombocytopenia is mandatory.

PMID- 19757696
TI  - Ptosis associated with monocular elevation deficiency.
AB  - OBJECTIVE: To document the various clinical features of ptosis associated with
      monocular elevation deficiency (MED) seen in patients, presenting to the
      Paediatric and Strabismus Unit, over a period of 2 years. METHODS: All patients
      seen with monocular elevation deficiency presenting to the Strabismus Clinic from
      January 2006 to December 2007 were examined and evaluated for presence of
      associated ptosis, jaw winking phenomenon and pseudoptosis. Patients having
      acquired causes of monocular limitation in elevation were excluded. RESULTS: A
      total of 22 patients having MED were seen. Out of these 50% were males (N = 11)
      and 50% females (N = 11). Twelve (54.54%) had MED in the left eye and 10 (45.45%)
      had MED in the right eye. Ptosis was present in the eye affected with MED in 16
      (72.72%) patients. Pseudoptosis was seen in 4 (18.18%) patients whereas no
      associated ptosis was noticed in 2 (9.09%) patients. Jaw winking phenomenon was
      present in 9 (40.90%) which comprise almost half (56%) the MED cases with ptosis.
      CONCLUSION: Careful clinical assessment for ptosis, pseudoptosis and jaw winking
      phenomenon before forced duction test, can help in planning the correct order of
      surgical management of patients having monocular elevation deficiency. The
      patient needs to be counseled regarding the multiple surgeries required according
      to associated clinical features present with MED.

PMID- 19757697
TI  - Scarring in acne patients--a study done at Isra University Hyderabad.
AB  - OBJECTIVES: To study the clinical presentation of acne in the Out Patient
      Department of Isra University Hospital. PATIENTS AND METHODS: A prospective study
      was done. The 100 patients with acne, who attended the Out Patient Department of
      Dermatology in Isra University Hospital, Hyderabad, from September 2007 to
      February 2008, were analyzed. RESULTS: In 100 patients with acne there were 65
      female and 35 male patients. The patient ages ranged from 11 to 35 years, most
      being in the age range from 15 to 19 years (mean, 18.70 +/- 4.50 years). Family
      history was positive in 49% of patients. Involvement of face was seen in 100% of
      patients. Scarring was observed in 59% patients. Premenstrual flare was seen in
      70% female patients. Most patients, 83% had pruritus in lesions. Face (cheeks,
      forehead and lower part of the face) were the most common sites to be involved.
      CONCLUSION: Acne is one of the common diseases, seen in the Out Patient
      Department, of Isra University Hospital. Study, concludes that female patients
      were more affected by acne and its complications like scarring as compared to the
      male patients.

PMID- 19757698
TI  - Overweight and obesity in students of a dental college of Karachi: lifestyle
      influence and measurement by an appropriate anthropometric index.
AB  - OBJECTIVE: To compare body mass index (BMI), waist circumference (WC), and body
      fat percentage (%BF), as index of overweight and obesity in young adults. We also
      intended to find an association between lifestyle behaviours and obesity.
      METHODS: A cross-sectional study was conducted at Fatima Jinnah Dental College,
      Karachi, during 2007 to 2008, with 192 first year dental students, (18-21years)
      of high socioeconomic class. All were questioned regarding lifestyle behaviours.
      Overweight and obesity were estimated by measuring %BF, BMI, and WC. For %BF,
      skinfold thickness was measured using skinfold calipers. BMI > or = 23.0-24.9
      kg/m2 was taken as overweight and > or = 25.0 kg/m2 as obese (Asians criteria
      proposed by Western Pacific Regional Office of World Health Organization). WC
      using Asian cutoff values for overweight and obesity were: males > or = 78 cm and
      > or = 90 cm; females > or = 72 cm and > or = 80 cm, respectively. Body fat
      percentage used to define overweight and obesity was: males 22.1-27.0 and > 27.1;
      females 27.1-32.0 and > 32.1, respectively. Pearson's correlation was done
      between the BMI, WC and %BF with statistical significance taken at P < 0.01.
      RESULTS: BMI (Expressed as mean +/- SD) in males and females was 23.82 +/- 3.88
      and 20.98 +/- 4.12 respectively. WC was 83.63 +/- 10.20 cm in males and 70.22 +/-
      9.36 cm in females. %BF was 22.32 +/- 6.27 in males and 28.73 +/- 6.65 in
      females, with an overall 60.8% females and 44.4% males found to be overweight or
      obese. Obesity was underpredicted by BMI when compared to skinfold calipers
      method. The obese were seen to skip breakfast more often [odds ratio (OR): 2.39],
      take frequent snacks (OR: 1.58), watch television more (OR: 1.58), and were
      physically less active than their non-obese counterparts. CONCLUSION: Body fat
      percentage using skinfold caliper is a reliable index of obesity. Lack of sleep
      and skipping of breakfast, are prominent promoters of obesity, in addition to
      other lifestyle behaviours.

PMID- 19757699
TI  - Prevalence of metabolic syndrome in renal transplant recipients--a single centre
      experience.
AB  - OBJECTIVE: To determine the prevalence of metabolic syndrome (MS) in renal
      transplant recipients (RTR) using the modified Asian National Cholesterol
      Education Programme-Adult Treatment Panel III (NCEP-ATP III) criteria. METHODS: A
      cross-sectional study was conducted on 200 RTRs between January 2008-August 2008.
      All were more than six months post transplant and above 18 years of age. Subjects
      with pre-transplant diabetes or New Onset Diabetes Mellitus after renal
      transplantation, with overt infections, dyslipidaemia or on lipid lowering
      medication and taking immunosuppressive drugs of the target organ inhibitor group
      as rapamycin, were excluded. The prevalence of MS was determined using the (NCEP
      ATP III) criteria modified for Asians which includes waist circumference,
      triglycerides, HDL cholesterol, blood pressure and fasting blood glucose.
      RESULTS: Of the 200 recipients studied, 87 (43.5%) had MS. There were 58 (39.4%)
      males and 29 (54.7%) females which shows female predominance. The mean age of the
      MS group was more then that of the non MS group (p < 0.0001). Hypertension and
      New Onset Diabetes Mellitus were prevalent more in MS group (p < 0.001 and p <
      0.0001 respectively). Mean serum creatinine was higher in MS group but there was
      no significant difference. The prevalence of MS was 4.5% in the first twelve
      months, with a rise in this figure to 41.3% between one to five years after
      transplantation. CONCLUSION: There is a high prevalence of MS in Renal Transplant
      Recipients specifically after one year of transplantation.

PMID- 19757700
TI  - The effect of Zizyphus spina-christi leaf extract on the isolated rat aorta.
AB  - OBJECTIVE: To investigate the effect of Zizyphus spina christi leaf
      hydroalcoholic extract (ZLHE) on the isolated rat aorta. METHODS: The rings of
      the endothelium intact and denuded thoracic aorta of Male and female Sprague
      Dawley rats were placed in Krebs-Henseleit solution to measure isometric
      contractile force. To study the involvement of voltage dependent L type calcium
      channels, concentration of 10 ?M verapamil was applied. Potassium chloride (50
      mM) was also added to the organ bath to compare the effect of extract and KCl.
      Potassium concentration of the extract at 2.5 and 5 mg/ml was measured. RESULTS:
      ZLHE induced contraction in the endothelium intact and denuded aorta dose
      dependently and significantly (P < 0.0001). Also, the response to extract at 5
      mg/ml was similar to that of KCl (50 mM). The application of verapamil reduced
      the contraction in the endothelium intact and denuded aorta by 66.7 +/- 3.1%
      (mean +/- SEM.) and 71.6 +/- 3.8% respectively. CONCLUSION: The results showed
      the vasoconstrictive effect of ZLHE which was not endothelium-dependent and
      largely blocked by verapamil, suggesting that the voltage-dependent Calcium
      channels play a pivotal role in the mechanism of action.

PMID- 19757701
TI  - Pattern of morphology in renal biopsies of nephrotic syndrome patients.
      Correlation with immunoglobulin and complement deposition and serology.
AB  - OBJECTIVE: To determine the morphological pattern in renal biopsies from
      nephrotic patients and their correlation with immunoglobulin and complement
      deposition as detected by immunofluorescence microscopy (IMF) and serology to
      arrive at correct diagnosis of glomerulonephritis (GN). METHODS: The study was
      carried out at the departments of Immunology and Histopathology, Sindh Institute
      of Urology and Transplantation (SIUT) from April 2007 to March 2008. A total of
      200 patients, including children and adults were included. All patients presented
      with nephrotic syndrome (NS). Clinical and laboratory investigations including
      serology were noted, renal biopsies performed and studied by light and
      immunofluorescence microscopy (IMF). RESULTS: Of 200 patients, 74 (37%) were
      children (< or = 18 years) and 126 (63%) adults (> or = 19 years). Mean age of
      children was 11.34 +/- 4.85 years (range 3-18 years) and that of adults was 35.44
      +/- 11.4 years (range: 19-70 years). The total percent change in L/M diagnosis
      after serological tests was 11.5% and after IMF studies, 23.5%. Combined
      serologic and IMF studies lead to 35% change in L/M diagnosis of the renal
      biopsies in nephrotic syndrome patients. CONCLUSION: Our results demonstrate that
      the ancillary techniques of IMF microscopy and serology are indispensable in the
      elucidation of final specific diagnosis causing nephrotic syndrome in a
      substantial number of cases and these should be employed routinely in the
      pathologic evaluation of renal biopsies. The study emphasizes the importance of
      combined approach in the investigation of renal biopsies in nephrotic syndrome.

PMID- 19757702
TI  - Clinical radiology research in Pakistan: from evidence to practice.
AB  - OBJECTIVE: To assess the clinical radiology research productivity in Pakistan by
      type of publication, sources of funding and name of journals. METHODS: A
      systematic search strategy using key words related to techniques and type of
      clinical radiology was carried out to identify various studies published in
      Indexed (Medline) and non-indexed (Pakmedinet) medical journals. RESULTS: Total
      of 397 studies were identified out of which 173(43%) from Medline (indexed
      database) and 220 (57%) from pakmedinet (Indexed and non- indexed database of
      Pakistan Medical journals). Original articles were 294 (74%) but most of them
      (68%) were published in non-indexed journals and significantly different from
      other articles types (case reports, short reports, review articles and letter to
      editors) (p-value < 0.001). No Randomized Controlled Trial was identified. No
      research was funded by any formal financial agency. As high as 78% of indexed
      studies were published by radiology centers of Sind province. Private hospitals
      having radiology department contributed significantly in indexed journals
      compared to government hospitals (p-value < 0.001). Majority (74%) of the studies
      were done by radiologists as compared to other non-radiology clinical colleagues
      (p-value < 0.001). The most preferred journal for publication was the Journal of
      Pakistan Medical Association (JPMA; N = 43) followed by Annals of King Edward
      medical college (Ann KEMC; N = 20). Australasian journal of radiology was the
      most preferred international journal for publication (Australas Radiol N = 3). No
      significant difference was found in radiology research production in terms of
      number of publication from and before the year 2000 (p-value 0.51). CONCLUSION:
      Clinical radiology research production from Pakistan is low in terms of quality
      and number. Only few studies reach the standard of publication in international
      medical journals. There is an urgent need of building the foundation of research
      programmes in radiology and strengthen research capacity building at facility and
      health policy level.

PMID- 19757703
TI  - Cancellation of surgery in patients attending the preoperative anaesthesia
      assessment clinic: a prospective audit.
AB  - OBJECTIVE: To find the causes of operating room cancellation in patients
      attending preoperative anaesthesia clinic and scheduled for surgery at our
      institution. METHODS: This audit included all those patients who presented to the
      pre anaesthesia clinic with their surgeries planned in the main operating rooms
      of our hospital. The duration of this audit was two months. Cancelled cases were
      identified from the operating room lists and the reasons for cancellations were
      categorized into above mentioned four factors. RESULTS: Fifty five (55)
      cancellations were identified; patient related factors (58%) were the most
      frequent cause followed by anaesthetic (22%), surgical (18.2%) and administrative
      (1.8%) factors. In patients related factors, most common causes appeared to be no
      shows and patient's financial issues. CONCLUSION: Most of the patient related
      factors were found to be uncontrollable. Anaesthetic related cancellations might
      be reduced with better communication between anaesthetist themselves and the
      surgeons. Overbooking of cases and other administrative issuescan be reduced with
      better organizational strategies

PMID- 19757704
TI  - Is Chaalia/Pan Masala harmful for health? practices and knowledge of children of
      schools in Mahmoodabad and Chanesar Goth, Karachi.
AB  - OBJECTIVE: To determine the practices and knowledge of harmful effects regarding
      use of Chaalia and Pan Masala in three schools of Mahmoodabad and Chanesar Goth,
      Jamshed Town, Karachi, Pakistan. METHODS: To achieve the objective a cross
      sectional design was used in three government schools of Mahmoodabad and Chanesar
      Goth, Jamshed Town, Karachi. Students of either gender drawn from these schools
      fulfilling the inclusion and exclusion criteria were interviewed using a pre
      coded structured questionnaire. Along with demographic data, questions regarding
      frequency of Chaalia and Pan Masala use, practices of this habit in friends and
      family and place of procurement of these substances, were inquired. Knowledge was
      assessed about harmful effects and its source of information. In addition,
      practices in relation to that knowledge were assessed. RESULTS: A total of 370
      students were interviewed over a period of six weeks, of which 205 (55.4%) were
      boys. The ages of the students were between 10 and 15 years. Thirty one percent
      of the fathers and 62% of the mothers were uneducated. The frequency of use of
      any brand of Chaalia was found to be 94% and that of Pan Masala was 73.8%. Eighty
      five percent of them were regular users. A large majority (88%) procured the
      substances themselves from near their homes. Ninety five percent of the children
      had friends with the same habits. Eighty four percent were using the substances
      in full knowledge of their families. Chaalia was considered harmful for health by
      96% and Pan Masala by 60%. Good taste was cited as a reason for continuing the
      habit by 88.5% of the children and use by friends by 57%. Knowledge about
      established harmful effects was variable. Knowledge about harmful effects was
      high in both "daily" and "less than daily users". CONCLUSION: The frequency of
      habits of Chaalia and Pan Masala chewing, by school children in lower socio
      economic areas is extremely high. The probable reasons for this high frequency
      are taste, the widespread use of these substances by family members and friends,
      low cost and easy availability.

PMID- 19757705
TI  - Old disease, new targets. Part-II, haematological malignancies.
AB  - In last two decades newer therapies in cancer treatment have emerged and have
      opened new horizons. New term of targeted therapy has emerged and for certain
      malignancies the paradigm has really changed after the introduction of these
      agents. We have learnt and have seen the outcome of some diseases after the
      addition of these monoclonal antibodies (MoABs) and tyrosine kinase inhibitors
      (TKIs). Rituximab a MoAB against CD-20 has really paved its role in the treatment
      of B-cell lymphomas and become the sort of standard therapy. The TKIs are newer
      agents available in a pill form and have inhibited many pathways at cellular
      level which are necessary for cancer development. Imatinib has really changed the
      prognosis and outcome of chronic myeloid leukemia (CML) remarkably. For those
      patients who develope intolerance to imatinib or their disease became resistant
      to the imatinib the newer agents like dasatinib and nilotinib are second line
      options. The major edge of these newer agents is more potency with low side
      effect profile. The major concern remains the cost.

PMID- 19757706
TI  - Subacute intestinal obstruction associated with a case of polycythemia vera--a
      rare combination.
AB  - Primary Polycythemia Vera (PV) is difficult to diagnose due to its varied and
      atypical 1 presentation. It is a myeloproliferative disorder which is managed
      conservatively. We submit a case report of a patient who was admitted in surgery
      with subacute intestinal obstruction due to compression by a massive splenic
      cyst. The investigations showed PV causing splenomegaly.

PMID- 19757707
TI  - Giant primary synchronously bilateral mesenteric dedifferentiated liposarcoma
      with hyperparathyroidism, hyperthyroidism, type-2 diabetes mellitus and
      hypertension.
AB  - Liposarcomas represent the single most common type of soft tissue sarcoma,
      occurring most commonly in the extremities and retroperitoneum. There is no
      relation between liposarcomas and multiple endocrine syndromes. We presented a 61
      year old woman with giant primary synchronously bilateral mesenteric
      dedifferentiated liposarcoma with hyperparathyroidism, hyperthyroidism, Type-2
      diabetes mellitus (T2DM) and hypertension. The mesenteric liposarcoma was
      reported neither synchronously bilateral nor with endocrine disorders. We must
      note if the patients' presentation was a co-incidence or an undescribed syndrome,
      waiting to be discovered.

PMID- 19757708
TI  - Epidural abscess and meningitis, a complication of spinal anesthesia in a
      bacteraemic patient.
AB  - Meningitis can be caused in experimental performing a lumbar puncture (LP) after
      bacteraemia. Several authors have speculated bacteraemic patient without having
      meningitis LP might actually cause meningitis. We meningitis and epidural abscess
      after spinal bacteraemic patient. A 57-year-old male, known admitted for below
      knee amputation, with infection and gangrene of the left foot. Intravenous were
      started and a below knee amputation date of admission under spinal anaesthesia.
      started having backache, fever and became operatively. A cerebrospinal fluid
      examination meningitis. Patient had seizures and developed failure. Cerebrospinal
      fluid smear showed the ie, Streptococcus agalactiae that grew on blood wound
      culture, sent at the time of admission. Resonance Imaging of LS spine showed an
      and was managed successfully with antibiotics.

PMID- 19757709
TI  - Vaginal clear cell adenocarcinoma with associated Mullerian duct anomalies, renal
      agenesis and situs inversus: report of a case with no known in-utero exposure
      with diethyl stilboestrol.
AB  - A 27 year old female presented with two months history of continuous vaginal
      bleeding. On evaluation, she was diagnosed as a case of vaginal clear cell
      adenocarcinoma (VCCA) along with associated Mullerian duct anomalies including
      didelphys uterus with double vagina; left sided renal agenesis and situs
      inversus. Although VCCA is strongly linked to in-utero exposure with Diethyl
      stillboestrol (DES), this patient had no known history regarding such exposure.
      Also, only a few cases have been described in the literature in which this tumour
      was seen in association with Mullerian duct anomalies and renal agenesis; in the
      absence of known DES exposure.

PMID- 19757710
TI  - Primary hypergonadotrophic hypogonadism, alopecia totalis, and mullerian
      hypoplasia: a clinical study.
AB  - Two sisters with primary hypergonadotrophic hypogonadism associated with alopecia
      totalis, streak ovaries, absent or rudimentary uterus and markedly hypo plastic
      internal and external genitalia are presented. Their parents were first cousins.

PMID- 19757711
TI  - Torture and doctors: an ethical dilemma?

PMID- 19757712
TI  - Frequency of hearing loss among textile industry workers of weaving unit in
      Karachi, Pakistan.
AB  - OBJECTIVE: To determine the frequency of hearing loss among textile industry
      workers of weaving department. To record the noise level in the weaving sections
      and to compare it with the international standards. To determine the awareness
      about the effects of noise on hearing amongst the workers and the protective
      measures adopted by them. METHODS: A cross-sectional study was carried out at
      weaving department of five renowned textile industries of Karachi. The study
      included 248 workers exposed to noise, through non-probability convenient
      sampling technique. Equivalent sound pressure level Leq was measured with the
      help of a Class-1 type digital sound level meter. Hearing status of the workers
      was assessed through questionnaire and clinical tests (WHISPER, RINNE'S and
      WEBER). RESULT: Results showed that noise level was in range of 88.4-104 dB(A).
      The questionnaire results showed that: (i) 92.7% of the workers were aware that
      high noise level cause speech interference. (ii) 57.2% were unaware about the
      effect of noise on health. (iii) 54.8% used ear protection devices. (iv) 22.5%
      did not respond well to whisper test while 16.9% were found to have defective
      hearing on the basis of Rinne's test and 17.4% through Weber's test. It was
      observed that hearing loss was significantly associated with working experience
      of more than 10 years (25%) and overtime (28.8%). CONCLUSION: The results of
      study establish the fact that noise level is more than acceptable limit of 85
      dB(A) for 8 hours exposure stipulated by OSHA.There is an immediate need to
      develop and implement noise regulations in Pakistan.

PMID- 19757713
TI  - A large chorioangioma causing intrauterine foetal demise.
AB  - Chorioangioma is a benign tumour of the placenta consisting of blood vessels and
      stroma that proliferates beyond normally developing chorionic villi. Most of the
      small tumours are asymptomatic but large placental tumours are associated with
      unfavourable outcomes for foetus and mother. We present a case of a 23 year old
      primigravida who had a large chorioangioma that lead to intrauterine foetal
      demise. Major complications and diagnostic tools for chrioangioma have been
      discussed.

PMID- 19757714
TI  - "Rota virus mortality: a dilemma for the developing world".

PMID- 19757715
TI  - "Collapsing FSGS, a need of awareness".

PMID- 19757716
TI  - The once and future debate on human embryonic stem cell research.

PMID- 19757717
TI  - Constitutional constraints on the regulation of cloning.

PMID- 19757718
TI  - Demythologizing the stem cell juggernaut.

PMID- 19757719
TI  - Beyond the low-hanging fruit: stem cell research policy in an Obama
      administration.

PMID- 19757720
TI  - Federal funding and the regulation of embryonic stem cell research: the Pontius
      Pilate maneuver.

PMID- 19757721
TI  - Cloning and stem cell debates in the context of genetic determinism.

PMID- 19757722
TI  - The ethics of embryonic stem cell research and the principle of "nothing is
      lost".

PMID- 19757723
TI  - Alternatives to embryonic stem cells and cloning: a brief scientific overview.

PMID- 19757724
TI  - Influencing policy to advance practice in ways that improve health.

PMID- 19757725
TI  - Commentary on child health and well-being... the policy-research interface.

PMID- 19757726
TI  - A critical examination of school-based occupational therapy collaborative
      consultation.
AB  - BACKGROUND: Although collaborative consultation has been widely adopted in school
      based occupational therapy practice, there is limited conceptual understanding of
      how collaboration contributes to educationally relevant outcomes for students
      with disabilities. Even without a clear understanding of the evidence related to
      school-based occupational therapy services, there continue to be decisions about
      funding and delivery of services. PURPOSE: This paper synthesizes and critically
      appraises the research literature on collaborative consultation services in
      school-based occupational therapy in order to provide program administrators with
      direction for critically examining decision making for service delivery in their
      districts. KEY ISSUES: Advancing occupational therapy practice in education
      settings requires a sound theoretical understanding of collaborative
      consultation. Distributed cognition offers a more robust understanding of the
      relationship between educator-therapist collaboration and outcomes of school
      based occupational therapy services. IMPLICATIONS: This review concludes with two
      fundamental conditions necessary for collaboration between educators and
      occupational therapists to flourish.

PMID- 19757727
TI  - Addressing pediatric wait times using the model of human performance technology.
AB  - BACKGROUND: When traditional approaches to waitlist management are unsuccessful,
      service managers and providers must consider alternatives. PURPOSE: To describe
      how the model of human performance technology was used to address an extensive
      pediatric waitlist. METHODS: Data were obtained from in-depth interviews with
      clinicians, educators, and parents and analyzed according to the model. FINDINGS:
      The need for a paradigm shift from a linear model of service delivery to a
      continuum of service was identified which could meet the unique needs of each
      child and family. Services include information, education, and supports, and all
      are grounded in principles of family-centred care. IMPLICATIONS: The model of
      human performance technology provided a systematic approach with which to reveal
      the reason for extensive wait times for pediatric occupational therapy service.
      The model suggested a paradigm shift from a linear model of care to a continuum
      of care grounded in family-centred care. Implementation and evaluation of this
      new care model are ongoing.

PMID- 19757728
TI  - Bridging research and policy in aging: issues of structure, process and
      communication.

PMID- 19757729
TI  - Client-centred home modifications improve daily activity performance of older
      adults.
AB  - BACKGROUND: Remaining at home is a high priority for many older adults, but the
      capacity to "age in place" often is threatened by environmental barriers.
      PURPOSE: To describe a client-centred occupational therapy home modification
      intervention program and examine the impact of the intervention on daily activity
      performance over time. METHODS: Using a competence-environmental press framework,
      a client-centred home modification program for older adults was implemented. In
      this quasiexperimental, single group prospective study, participants'subjective
      ratings of daily activity performance were evaluated before and after the
      intervention (baseline/post/post). FINDINGS: After home modification,
      participants'perception of their daily activity performance at home improved
      significantly and was maintained 2 years post-modification. IMPLICATIONS: Home
      modification may benefit older adults attempting to age in place.

PMID- 19757730
TI  - Criterion validity of a home health aide's algorithm for recommending bathroom
      equipment.
AB  - BACKGROUND: Occupational therapists are experts at adapting bathroom
      environments. However, to increase access to services, the algorithm "Prealables
      aux soins d'hygiene" (French for "Prerequisites for bathing care") has been
      developed to be used by trained home health aides to recommend bathroom
      equipment. PURPOSE: The purpose of this study was to assess the criterion
      validity of the algorithm by measuring the level of agreement between an
      occupational therapist's recommendations (gold standard) and those made by four
      home health aides using the algorithm. METHODS: Community-living adults with
      bathing difficulties (n = 96) were visited by both types of evaluators. FINDINGS:
      Home health aides correctly identified clinical situations in which they should
      feel confident about their ability (sensitivity: 96%, specificity: 69%) and,
      apart from type of bathing seat (K(W) = 0.63 [0.52; 0.75]), agreement between
      recommendations varied from substantial to almost perfect (delta > or = 0.72).
      IMPLICATIONS: Results increase confidence in the algorithm, but other studies are
      needed to ensure population safety and fulfil the occupational therapist's
      obligations.

PMID- 19757731
TI  - Surgical advances in periacetabular osteotomy for treatment of hip dysplasia in
      adults.
AB  - INTRODUCTION: Hip dysplasia is characterized by an excessively oblique and
      shallow acetabulum with insufficient coverage of the femoral head. It is a known
      cause of pain and the development of early osteoarthritis in young adults. The
      periacetabular osteotomy is the joint-preserving treatment of choice in young
      adults with symptomatic hip dysplasia. The surgical aim of this extensive
      procedure is to reorient the acetabulum to improve coverage and eliminate the
      pathological hip joint mechanics. Intraoperative assessment of the achieved
      acetabular reorientation is therefore crucial. The "classic" surgical approaches
      for the periacetabular osteotomy inflict extensive trauma to the tissues and some
      involve detachment of muscles. The type of surgical approach may affect the
      occurrence of complications, duration of surgery, intraoperative blood loss,
      transfusion requirements, and length of hospital stay. The aims of the PhD thesis
      were I) to assess the outcome of a new, minimally invasive transsartorial
      approach for periacetabular osteotomy; II) to compare the minimally invasive
      approach with the previously used "classic" ilioinguinal approach; and III) to
      assess the reliability of a novel device for intraoperative assessment of the
      achieved acetabular reorientation. METHODS: Three studies underly this PhD
      thesis. In studies I and II, the experience with the minimally invasive and
      ilioinguinal approaches was retrospectively assessed by database inquiry and
      evaluation of radiographic material. Data regarding patient demographics, patient
      history, intraoperative measures and complications was recorded in a validated
      database. Center-edge and acetabular index angles were measured in preoperative
      and postoperative pelvic radiographs to assess preoperative dysplasia and the
      achieved acetabular reorientation. The well-defined study groups consisted of 94
      and 263 periacetabular osteotomies in studies I and II, respectively. In study
      III, intraoperative angle measurements were carried out prospectively in 35
      periacetabular osteotomies. The obtained measures (center-edge and acetabular
      index angles) were compared with those of postoperative pelvic radiographs.
      Furthermore, a cadaver study was conducted to evaluate intra- and interobserver
      variability of the device and to assess whether pelvic positioning influenced the
      variability of measurements. The applied methodology was critically reviewed.
      RESULTS: Study I--The minimally invasive approach had the following outcome. The
      mean duration of surgery was 73 min and the median intraoperative blood loss was
      250 ml. Blood transfusion was required following 3% of the procedures. There were
      no cases of moderate or severe technical and neurovascular complications, and the
      achieved center-edge and acetabular index angles suggest that optimal
      reorientation can be achieved. Hip joint survival with total hip arthroplasty as
      the end point was 98% at 4.3 years. Study II--When compared with the outcome of
      the ilioinguinal approach, the procedures performed by using the minimally
      invasive approach had a statistically significant shorter duration of surgery,
      less intraoperative blood loss and hemoglobin reduction, and fewer transfusion
      requirements. The achieved reorientation was comparable between groups. There
      were no cases of moderate or severe complications in the minimally invasive group
      and three cases (3%) of arterial thrombosis in the ilioinguinal group. At follow
      up 4.9 years after hip joint surgery, survival rates were 97% in the minimally
      invasive group and 93% in the ilioinguinal group. Study III--Intraoperatively
      obtained angle measures differed less than +/- 5 degrees from measurements on
      postoperative pelvic radiographs, and the intra- and interobserver variability of
      the device was confined well within +/-5 degrees. Positioning did not influence
      the variation of angle measurements beyond intraobserver variability of the
      device. INTERPRETATION: The new minimally invasive transsartorial approach
      appears to be a safe technique, allowing optimal acetabular reorientation, and
      seems to minimize tissue trauma. In addition, short-term hip joint survival rate
      is encouraging. The outcome compares favorably with that of the ilioinguinal
      approach, and the results support continued use of the minimally invasive
      approach for periacetabular osteotomy. Optimal reorientation of the acetabulum is
      crucial in periacetabular osteotomy. The novel measuring device is a potentially
      helpful tool for intraoperative assessment of center-edge and acetabular index
      angels. It is simple to use and facilitates repeated reliable angle measurements
      during acetabular reorientation, making intraoperative radiographs unnecessary.
      The new, minimally invasive approach and the novel measuring device represent
      important surgical advances in contemporary periacetabular osteotomy.

PMID- 19757732
TI  - Perthes' disease in Norway. A prospective study on 425 patients.

PMID- 19757733
TI  - Periodontal and periimplant maintenance: a critical factor in long-term treatment
      success.
AB  - Periodontal maintenance (PM) is a critical factor in the long-term success of
      both periodontal and dental implant therapy. Studies have shown both modern
      periodontal and dental implant therapies are effective in maintaining natural
      teeth and replacing lost teeth, respectively. However, without a regular program
      of clinical reevaluation, plaque control, oral hygiene instruction, and
      reassessment of biomechanical factors, the benefits of treatment often are lost
      and inflammatory disease in the form of recurrent periodontitis or
      periimplantitis may result. This article reviews the goals, types, and
      appropriate frequency of PM in periodontal and dental implant therapy, as well as
      the incidence and etiology of periimplant disease and strategies for management
      when recurrent disease develops during the maintenance phase of treatment.

PMID- 19757734
TI  - Placement of immediate implants and a fixed provisional restoration to replace
      the four mandibular incisors.
AB  - A new approach to the replacement of four mandibular incisors with localized,
      chronic, severe periodontitis is proposed in this clinical report. Their
      replacement with immediately placed implants and a nonocclusally loaded
      provisional restoration is a simple, predictable, and successful treatment
      modality. Data from 10 consecutive clinical cases are presented, and a 100%
      implant survival rate is reported for a 6-year period of follow-up. Treatment
      outcomes for this approach compare favorably with alternative treatment options
      and should be considered an important primary treatment option for most patients
      requiring the replacement of the four mandibular incisors.

PMID- 19757735
TI  - Anterior wear: orthodontic and restorative management.

PMID- 19757737
TI  - Connecting teeth to implants: a critical review of the literature and
      presentation of practical guidelines.
AB  - Historically, connecting a tooth to an implant to function as an abutment to
      replace a missing tooth was discouraged. It was believed differences in mobility
      patterns of a tooth and an implant would result in the prosthesis being
      cantilevered off the implant, thereby stressing the implant. Several papers
      concluded increased stress caused technical and biologic complications, which led
      to a decreased survival rate for a tooth-implant supported prosthesis (TISP) when
      compared with an implant-only supported prosthesis (ISP). However, problems
      attributed to TISPs may have been overstated. This paper reviews animal studies
      and human clinical trials that monitored successful use of TISPs. In addition,
      numerous issues are addressed that question the data, which have been interpreted
      to indicate that a tooth should not be connected to an implant. Recommendations
      are made to facilitate attaining high success rates with TISPs.

PMID- 19757736
TI  - Strength of evidence relating periodontal disease and atherosclerotic disease.
AB  - This review assesses the strength of evidence relating periodontal disease and
      atherosclerotic disease (ischemic heart disease, peripheral arterial disease, and
      ischemic stroke). Periodontal disease and atherosclerotic disease may be linked
      causally, or their relationship could be explained, wholly or partially, by
      common risk factors. Many potential pathways for the relationship have been
      postulated. This article focuses on evaluating the overall body of evidence,
      according to the following standard causal inference criteria: strength of
      association, dose-response relationship, time sequence, consistency, specificity,
      biologic plausibility, and independence from confounding. Each criterion is
      reviewed and evaluated against the existing literature. In summary, the overall
      strength of evidence for causal criteria for the relation between periodontal
      disease and atherosclerotic disease is as follows: The magnitude and consistency
      of the association is stronger for ischemic stroke (and is low for ischemic heart
      disease), some evidence for dose response exists, time sequence has been
      established with more evidence for stroke, and there is definitely biologic
      plausibility for all these associations. Independence from confounding is also
      stronger for ischemic stroke and peripheral arterial disease. Specificity is not
      established for any of these associations, as there are multiple risk factors for
      atherosclerotic disease; however, specificity is not considered an important
      criterion for causality. Because the underlying pathogenesis of atherosclerosis
      is common across the diseases, it is likely that if additional studies show
      consistent associations, periodontal disease may be an important independent
      causal risk factor for atherosclerotic disease, especially for ischemic stroke.

PMID- 19757738
TI  - Implants.

PMID- 19757739
TI  - Collaboration and conflict management: a brief review of current thought.

PMID- 19757740
TI  - Responding to a disaster.

PMID- 19757741
TI  - What have I done?

PMID- 19757742
TI  - Red Cross celebrates 100 years of nursing.

PMID- 19757743
TI  - Maine to Nepal nursing.

PMID- 19757745
TI  - Mary Glover Lecture presented at the CANN Conference, Halifax, N.S., June 2009.

PMID- 19757744
TI  - Midline location of tumour is a risk factor for postoperative vomiting in
      children requiring posterior fossa tumour resection.
AB  - Children requiring posterior fossa brain tumour surgery form a unique and
      significant neuro-oncology population. Postoperative vomiting (POV) is a problem
      for these children. Also, severe vomiting that is refractory to treatment has
      been seen clinically in these children, but it is not well described in the
      literature. A subgroup of children requiring surgery for posterior fossa brain
      tumours (n=153) from a larger six-year retrospective chart audit (n=249) at two
      Canadian children's hospitals were reviewed for the presence of no, mild,
      moderate, and severe POV. Inter-rater reliability was established at 94%
      following a blinded process of comparing POV severity rankings between two data
      collector/researchers. Discrepancies were resolved through discussion in order to
      establish a consensus severity score. Findings from multivariable logistic
      regression analyses indicated that when age and intraoperative use of ondansetron
      were controlled for, the location of a tumour in a midline location had no
      overall effect (adjusted OR=1.37, 95% confidence interval: 0.64-2.96, p=0.43),
      but greater odds of severe vomiting (adjusted OR=7.08, 95% confidence interval:
      2.56-19.64, p<0.001). These results support theories of modulation of vomiting by
      the medullary midline and clinical observations that children with midline
      posterior fossa tumours are at greater risk for severe refractory vomiting. The
      development of clinical practice guidelines and further research to study the
      effectiveness of novel, multimodal antiemetic therapies are required for this
      patient population.

PMID- 19757746
TI  - Intrathecal baclofen and pregnancy: implications for clinical care.
AB  - Pregnancy in patients with intrathecal baclofen (ITB) pumps is rare. To our
      knowledge, only five reported cases of pregnancy exist in the literature. Thus,
      there is little experience to inform health care practitioners about the maternal
      and fetal safety of ITB or its efficacy throughout pregnancy. There are no
      reports of a pregnant female with an implanted ITB pump having a spontaneous,
      vaginal delivery at term. As far as we know, this is the first case described in
      the literature. Additionally, current literature does not address clinical
      implications for these patients. This paper reviews literature to date and
      presents unique aspects of our patient. It also discusses clinical implications
      for treating a pregnant patient with an ITB pump. The intent of this paper is to
      advance our body of knowledge in caring for pregnant clients with ITB pumps and
      reassure families about the safety and efficacy of this treatment.

PMID- 19757747
TI  - [Increase in the number of people with diabetes mellitus: need for a master
      plan].

PMID- 19757748
TI  - [The coming diabetes tsunami: the Netherlands should exploit its lead].

PMID- 19757749
TI  - [Diabetes mellitus in the Netherlands: estimate of the current disease burden and
      prognosis for 2025].

PMID- 19757750
TI  - [Variable presentation of antiglomerular basement membrane (anti-GBM) disease:
      rapid recognition vitally important].

PMID- 19757751
TI  - [Raynauds phenomenon. Diagnosis and treatment].

PMID- 19757752
TI  - [Diagnostic image. A breastfeeding woman with a painful, blue nipple].

PMID- 19757753
TI  - [Traumatic atlas fracture in a child following fall on head].

PMID- 19757755
TI  - [Cocaine use and sudden death: excited delirium syndrome].

PMID- 19757756
TI  - [Clinical reasoning and decision making in clinical practice: a boy with fatigue
      and abdominal pain].

PMID- 19757757
TI  - [Hyperchloremic metabolic acidosis in a patient with an ureteroileostomy
      according to Bricker].

PMID- 19757758
TI  - [Focal liver lesion after normal pregnancy].

PMID- 19757759
TI  - [Diagnostic image. A woman with a growth at a toe nail].

PMID- 19757760
TI  - [Narrative neurology: access to the patients' experiences].

PMID- 19757761
TI  - Complexity science--how may it help oncology nurses?

PMID- 19757762
TI  - Cancer survivorship: creating a national agenda.

PMID- 19757763
TI  - The human papillomavirus vaccine: an oncology nursing issue.
AB  - In Canada, approximately 1,500 women are diagnosed with cervical cancer every
      year, and 581 will die of the disease (WHO/ICO Information Centre on HPV and
      Cervical Cancer, 2007). The importance of preventing cervical cancer is clear, as
      the effects that this disease has on the lives of women and their families
      regardless of culture, sex, nationality or country is evident. With the recent
      media attention and release of the Human Papillomavirus (HPV) vaccine in Canada,
      it is crucial that oncology nurses understand HPV, its role in the development of
      cervical cancer, and the HPV vaccine. A brief overview of HPV and its involvement
      in the development of cervical cancer will be discussed in this paper. In
      addition, information on the HPV vaccine and its implications, as well as the
      current policy for the vaccine in Canada will be addressed. It will become
      evident how the role of the oncology nurse, as an educator and advocate regarding
      the implementation of this vaccine is crucial for successful acceptance of this
      vaccine. Finally, future implications of the vaccine and avenues of research will
      be touched upon.

PMID- 19757764
TI  - Helene Hudson Memorial Lectureship CANO 2008.
AB  - One in nine women will develop breast cancer in her lifetime (Canadian Cancer
      Society, 2007). Hereditary breast cancer accounts for only five to 10 per cent of
      all breast cancers. However, women carrying a single high-penetrance gene
      mutation have a 40% to 80% chance of developing breast cancer (Fackenthal &
      Olopade, 2007). Most of these breast cancers occur in women under the age of 50.
      The BRCA 1 gene mutation was first reported in 1994, and the BRCA 2 gene mutation
      in 1995. The BRCA 2 gene mutation is often carried in males, and accounts for
      approximately six per cent of male breast cancer. Women with this gene mutation
      have a lifetime risk of developing breast cancer of between 50% and 85%, a second
      breast cancer of between 30% and 50%, and ovarian cancer between 10% and 20%.
      Each parent with the BRCA 2 gene mutation has a 50% chance of passing this gene
      mutation to their children (National Cancer Institute, 2006). The emotional
      impact of receiving cancer risk information such as this is difficult to predict.
      When presented with information about risk-reduction surgery, chemoprevention,
      risk avoidance and increased screening, how does one make decisions? Walk with
      me, as I share how my family discovered we carry the Icelandic founder gene
      mutation, the steps we took together during the testing process, and the decision
      making by the family members who tested positive. We'll focus on my sister Rita-
      ordinary days, an extraordinary woman.

PMID- 19757765
TI  - [Monteregie Comprehensive Cancer Care Centre: integrating nurse navigators in
      Monteregie's oncology teams: the process. Part 2].
AB  - Quebec's Oncology Nurse Navigators (or "IPOs" after their French acronym) have
      been integrated in the entire Monteregie health care region. They have been
      agents of change mandated with implementing a philosophy of care that centres on
      the patients and their families, and is delivered by oncology teams. The goal of
      this second article is to describe the role of IPOs in practice, the problems
      encountered in the various contexts and the solutions brought forward to
      facilitate their integration. The training of IPOs, the support they receive from
      administrators, the deployment of interdisciplinary teams dedicated to oncology,
      the holding of regular structured interdisciplinary meetings and the training of
      professionals, and development of standardized work instruments are discussed.
      The observed impacts of introducing IPOs will also be examined.

PMID- 19757766
TI  - I'm nursing as fast as I can: how the history of cancer and cancer care informs
      the future of oncology nursing.

PMID- 19757767
TI  - Developing a national strategy for chemotherapy administration for oncology
      nurses in Canada.

PMID- 19757768
TI  - Pilot project for nutritional screening in persons with lung cancer.

PMID- 19757769
TI  - Perspectives on waiting on lung cancer.

PMID- 19757770
TI  - Ann Syme, BSN, MSN, PhD(c): a mentor and leader in palliative cancer care.

PMID- 19757771
TI  - Enzymatic synthesis and structural characterization of 13C, 15N-poly(ADP-ribose).
AB  - Poly(ADP-ribose) is a significant nucleic acid polymer involved with diverse
      functions in eukaryotic cells, yet no structural information is available. A
      method for the synthesis of (13)C, (15)N-poly(ADP-ribose) (PAR) has been
      developed to allow characterization of the polymer using multidimensional nuclear
      magnetic resonance (NMR) spectroscopy. Successful integration of pentose
      phosphate, nicotinamide adenine dinucleotide biosynthesis, and cofactor recycling
      pathways with poly(ADP-ribose) polymerase-1 permitted labeling of PAR from (13)C
      glucose and (13)C, (15)N-ATP in a single pot reaction. The scheme is efficient,
      yielding approximately 400 nmoles of purified PAR from 5 mumoles ATP, and the
      behavior of the synthetic PAR is similar to data from PAR synthesized by cell
      extracts. The resonances for (13)C, (15)N-PAR were unambiguously assigned, but
      the polymer appears to be devoid of inherent regular structure. PAR may form an
      ordered macromolecular structure when interacting with proteins, and due to the
      extensive involvement of PAR in cell function and disease, further studies of PAR
      structure will be required. The labeled PAR synthesis reported here will provide
      an essential tool for the future study of PAR-protein complexes.

PMID- 19757772
TI  - One-pot room-temperature synthesis of single-crystalline gold nanocorolla in
      water.
AB  - A room-temperature nanocarving strategy is developed for the fabrication of
      complex gold nanoplates having corolla- and propeller-like architectures. It is
      based on the simultaneous growth and etching of gold nanoplates in aqueous
      solution, which occur in the course of photoreduction of Au(OH)(4)(-) ions. The
      presence of bromide ion, poly(vinylpyrrolidone) (PVP), and molecular oxygen is
      indispensable, where bromide ions play multiple roles. First, they promote
      formation of nanoplate structures by forming adlayers on the fcc(111) surface.
      Second, they facilitate oxidative dissolution of gold nanocrystals by converting
      the oxidized Au(I) species to soluble AuBr(2)(-) ions, which lead to the
      formation of ultrathin nanocrevasses. PVP also stabilizes the nucleation of gold
      nanoplates. Although the overall reactions proceed in one-pot, the crystal growth
      and etching show interplay and occur with different kinetics due to changes in
      the concentration of Au(OH)(4)(-) and other species with time. Corolla- or
      propeller-like gold nanoplates formed under these conditions are single
      crystalline, as indicated by selected area electron diffraction patterns and the
      observation of moire fringes. The morphology of corolla- or propeller-like gold
      nanoplates is controllable depending on the concentration of bromide ion and PVP
      in the aqueous mixture. On the basis of these results, a preliminary mechanism is
      proposed which involves the concurrent crystal growth and oxidative etching on
      the surface of nanocrystals.

PMID- 19757773
TI  - Iridium(III) catalyzed diastereo- and enantioselective C-H bond
      functionalization.
AB  - Iridium(III)-salen complexes were found to efficiently catalyze the
      enantioselective C-H carbene insertion. The insertion reaction at the alpha
      position of tetrahydrofuran or at the methylene of 1,4-cyclohexadiene proceeded
      with high enantio- (up to 99%) and diastereoselectivity (up to >20:1 dr; in the
      former reaction) by using an appropriate combination of complex (1, 2, or 3) and
      alpha-diazoacetate (alpha-aryl-alpha-diazoacetates or alpha-diazopropionate) as
      the carbene source.

PMID- 19757774
TI  - Why the chromyl bond is stronger than the perchromyl bond in high-valent
      oxochromium(IV,V) complexes of tris(pentafluorophenyl)corrole.
AB  - Resonance Raman (RR) spectroscopy and density functional theory (DFT)
      calculations of oxochromium(IV,V) derivatives of 5,10,15
      tris(pentafluorophenyl)corrole (tpfpc) are shown to provide useful information
      about the relative strength of the metal-oxo bond in high-valent Cr(IV) versus
      Cr(V) corroles. Isotope labeling of the terminal oxo group with (18)O revealed
      that the Cr(V)-oxo (perchromyl) stretch of (tpfpc)Cr(V)O vibrates at a frequency
      of 986 cm(-1) in carbon disulfide, consistent with a triply bonded Cr(V)[triple
      bond]O unit. In contrast, an acetonitrile solution produced RR scattering that
      rapidly changed with the number of scans collected and eventually became
      dominated by an (18)O-sensitive vibration at a significantly higher frequency of
      1002 cm(-1). On the basis of DFT calculations and the observed (18/16)O isotopic
      shift, we assigned this new RR band at 1002 cm(-1) in acetonitrile as the Cr(IV)
      oxo (chromyl) stretch of the autoreduced [(tpfpc)Cr(IV)O](-) product, which
      previously has been shown to form only during the course of the oxygen atom
      transfer (OAT) reaction with triphenylphosphine in acetonitrile or in the
      presence of a reducing chemical (cobaltocene) and electrochemical agents in other
      solvents. Consequently, RR observations indicate that the pi-bonding character of
      the chromyl bond is actually increased relative to that of the perchromyl bond,
      which is of interest if the beneficial role of acetonitrile in OAT catalysis by
      high-valent oxochromium(IV,V) corroles is to be elucidated.

PMID- 19757775
TI  - Photoemission and photoabsorption spectroscopy of glycyl-glycine in the gas
      phase.
AB  - The high-resolution outer and inner valence band (VB) spectra, as well as core
      level X-ray photoemission (XPS) and near edge X-ray absorption fine structure
      (NEXAFS) spectra at the carbon, nitrogen, and oxygen K-edges of glycyl-glycine in
      the gas phase have been measured, and the results interpreted by means of ab
      initio calculations. By comparison with our previous glycine spectra, the
      features characteristic of the peptide bond in the carbon, nitrogen, and oxygen
      XPS and NEXAFS spectra of glycyl-glycine have been identified and assigned. The K
      edge NEXAFS spectra at all edges were found to be in reasonable agreement with
      published electron energy loss spectra, but showed more prominent structure due
      to the higher resolution. Effects on the nitrogen K-edge NEXAFS spectrum of
      glycyl-glycine due to intramolecular hydrogen bonding were observed. The N(NH(2))
      1s --> pi*(CN) resonance shifts to 0.6 eV lower energy, due to internal hydrogen
      bonding between the NH(2) and NH groups.

PMID- 19757776
TI  - Elastic depolarization of OH(A) by He and Ar: a comparative study.
AB  - Two color polarization spectroscopy has been employed to measure the collisional
      depolarization of OH(A(2)Sigma(+), v = 1) by He and Ar. Complementary experiments
      using Zeeman quantum beat spectroscopy have also been performed to determine
      separately the cross sections for rotational energy transfer (RET) out of
      selected rotational levels of OH(A, v = 0) + Ar, as well as those for elastic
      depolarization. This has been achieved by dispersing the emission, so as to
      observe a single fluorescence transition. Elastic depolarization of OH(A) by Ar
      is found to be significant with that for loss of rotational alignment exceeding
      that for loss of orientation. In the case of OH(A) + He, the polarization
      spectroscopy measurements suggest that elastic depolarization plays a relatively
      minor role in the loss of the polarization signal compared with RET. The
      experimental data for OH(A) + Ar are compared in detail with the results of quasi
      classical trajectory calculations that accommodate the effects of electron spin.
      These classical calculations are assessed against the results obtained using full
      close-coupled open shell quantum mechanical scattering methods. Overall the level
      of agreement between the two experiments, and between experiment and theory, is
      very reasonable. Surprisingly, at low N the elastic depolarization cross sections
      for OH(A) + Ar are found to be quite similar in magnitude to those observed for
      OH(X) + Ar despite the fact that the well depth in the latter system is
      considerably smaller than that for OH(A)-Ar. However, for OH(A) + Ar the
      depolarization cross sections are insensitive to N in the range 1-14. It is
      proposed that this behavior partly reflects the relatively anisotropic nature of
      the potential energy surface, which exhibits deep wells of different depths at
      the two linear configurations OH(A)-Ar and Ar-OH(A), and partly the nature of
      elastic depolarizing collisions, which must occur with a velocity component
      perpendicular to the plane of rotation of the diatomic molecule.

PMID- 19757777
TI  - A divergent synthesis of very large polyphenylene dendrimers with iridium(III)
      cores: molecular size effect on the performance of phosphorescent organic light
      emitting diodes.
AB  - This is a first report on a novel divergent procedure to synthesize higher
      generation polyphenylene dendrimers with an Ir(III) core up to G4, which up to
      now is the largest Ir(III) dendrimer, having a molecular diameter of 8 nm. Our
      synthetic method provides a much higher yield (>80%) than earlier reported
      traditional convergent strategies (<35%). Moreover, with a stepwise synthesis,
      the molecular sizes are controlled by different dendrimer generations from G1
      (R(1) approximately 15 A) to G4 (R(4) approximately 40 A). In this case,
      polyphenylene dendrons are used as a "matrix" which prevent iridium
      phosphorescent cores from triplet-triplet annihilation and improve their
      photoluminescence quantum yields (PLQYs). All dendrimers show strong
      phosphorescence at room temperature, and interestingly, their PLQYs tend to
      increase with subsequent generations up to 36% for G4 in solid state, almost 4
      times of that of the nondendritic iridium complex. We also fabricated all
      generation dendrimers in phosphorescent organic light-emitting diodes (PhOLEDs)
      and investigated the relationship between the Ir(III) dendrimer sizes and the
      device performances. Our results indicate that dendrimer G3 possesses the highest
      efficiency device compared to other generation dendrimers, since its appropriate
      dendrimer size (R(3) approximately 30 A) can not only prevent intermolecular
      triplet-triplet annihilation, thereby increasing the PLQY, but also provide an
      effective charge carrier mobility from the periphery to the Ir(III) core.

PMID- 19757778
TI  - Orthogonal coordinates and hyperquantization algorithm. The NH3 and H3O+ umbrella
      inversion levels.
AB  - In order to describe the umbrella inversion mode, which is characteristic of
      AB(3)-type molecules, we have introduced an alternative hyperspherical coordinate
      set based on a parametrization of Radau-Smith orthogonal vectors and have
      considered constraints which allow us to enforce the C(3v) symmetry. Structural
      properties and electronic energies at equilibrium and barrier configurations have
      been obtained at MP2 and CCSD(T) levels of theory. Energy profiles have been
      calculated using the CCSD(T) method with an aug-cc-pVQZ basis set. The NH(3) and
      H(3)O(+) umbrella inversion levels are obtained by the hyperquantization
      algorithm for a one-dimensional calculation, using a specially defined hyperangle
      as the inversion coordinate. The results are compared with experimental and
      theoretical energy levels, in particular, with those obtained by calculations
      based on two-dimensional models. The emerging picture of the umbrella inversion
      based on this hyperangular coordinate compares favorably with respect to the
      usual valence-type description.

PMID- 19757780
TI  - Structure, stability, and thermochemistry of the fullerene derivatives C(64)X(6)
      (X = H, F, Cl).
AB  - The geometrical structures, electronic properties, and stabilities of the
      unconventional fullerene derivatives C(64)X(6) (X = H, F, Cl) have been
      systematically studied by the first-principle calculations based on the density
      functional theory. The fullerene derivatives 1911(2)-C(64)X(6) generated from the
      pineapple-shaped C(64)X(4) are predicted to possess the lowest energies. The
      other two X atoms are added to the carbon atoms with the highest local strain
      assessed by the pyramidalization angles. The calculations of the nucleus
      independent chemical shifts suggest that the aromaticity of C(64)X(6) affects the
      stability order of the derivative isomers. To address why C(64)H(6) was not
      observed in the experimental study of Wang et al. (J. Am. Chem. Soc. 2006, 128,
      6605) and if the halogenated derivatives C(64)X(6) (X = F, Cl) can be
      synthesized, thermochemical analysis of the reaction C(64)X(4) + X(2) -->
      C(64)X(6) was also performed. The results indicate that the formation of
      C(64)H(6) and C(64)Cl(6) is not favored at high temperatures. The former may be a
      reason why C(64)H(6) was not found in the experiment. In sharp contrast, the
      Gibbs free energy change to form C(64)F(6) is found to be -23.29 kcal/mol at 2000
      K, suggesting that this compound may be formed and detected in experiments. The
      NMR and IR spectra of 1911(2)-C(64)F(6) are sequentially calculated and presented
      to facilitate future experimental identification.

PMID- 19757781
TI  - Quantum mechanical and NMR studies of ring puckering and cis/trans-rotameric
      interconversion in prolines and hydroxyprolines.
AB  - Nuclear magnetic resonance (NMR) and quantum mechanical (QM) studies have been
      carried out for proline (Pro) containing peptides: N-acetyl-l-proline (AcProOH)
      and N-acetyl-4-hydroxy-l-proline (AcHypOH). Preliminary results of variable
      temperature NMR measurements for Gly-Pro-Gly-Gly (GPGG), Val-Ala-Pro-Gly (VAPG),
      and Ala-Pro-Gly-Trp amide acetate salt (APGW) are also reported. The effect of
      solvent (D(2)O, DMSO-d(6) and CD(3)CN) on the pyrrolidine ring conformation and
      cis/trans-rotamerisation along the amide bond preceding Pro was investigated by
      temperature dependent NMR followed by detailed transition state (TS) searches for
      both conformational equilibria using QM methods. The results revealed the
      energetic characteristics of the TS, which were in satisfactory agreement with
      NMR, and the corresponding TS geometries, which are not available from
      experiment. The most remarkable feature of the cis/trans-rotamerisation is that
      the amide nitrogen in AcProOH and AcHypOH adopts a tetrahedral geometry in the
      TS. Various HF, DFT, and MP2 calculations together with implicit solvation
      modeling were employed in order to identify the most suitable QM protocols for
      reliable predictions of the geometry and the relative energies of the
      conformations of Pro and Hyp containing peptides in aqueous solution. Solution
      NMR results were used for the verification of the reliability of the QM
      predictions. The results indicate that the MP2 calculations combined with
      implicit solvation models are reasonably accurate in reproducing NMR measured
      populations of four different conformations of either AcProOH or AcHypOH in
      different solvents, whereas HF and DFT B3LYP calculations were significantly less
      accurate.

PMID- 19757782
TI  - Biomimetic conformation-specific assembly of proteins at artificial binding sites
      nanopatterned on silicon.
AB  - Biomolecules such as enzymes and antibodies possess binding sites where the
      molecular architecture and the physicochemical properties are optimum for their
      interaction with a particular target, in some cases even differentiating between
      stereoisomers. Here, we mimic this exquisite specificity via the creation of a
      suitable chemical environment by fabricating artificial binding sites for the
      protein calmodulin (CaM). By downscaling well-known surface chemical modification
      methodologies to the nanometer scale via silicon nanopatterning, the Ca(2+)-CaM
      conformer was found to selectively bind the biomimetic binding sites. The
      methodology could be adapted to mimic other protein-receptor interactions for
      sensing and catalysis.

PMID- 19757783
TI  - Synthesis, structure, and reaction chemistry of samarium(II), europium(II), and
      ytterbium(II) complexes of the unsymmetrical benzamidinate ligand
      [PhC(NSiMe(3))(NC(6)H(3)Pr(i)(2)-2,6)](-).
AB  - Neutral mononuclear lanthanide(II) bis(amidinate) complexes [LnL(2)(THF)(x)] [L =
      PhC(NSiMe(3))(NC(6)H(3)Pr(i)(2)-2,6)(-); Ln = Sm, x = 2 (3); Ln = Eu, x = 2, (4);
      Ln = Yb, x = 1 (5)] were synthesized by the reaction of the appropriate
      LnI(2)(THF)(2) with potassium amidinate [KL](n) (2). The reduction chemistry of 3
      5 was also examined. The reaction of the Sm(II) and Eu(II) amidinates 3 and 4
      with diphenyl dichalcogenides PhEEPh (E = Se, Te) led to the binuclear
      lanthanide(III) amidinate-chalcogenolate complexes [LnL(2)(mu-EPh)](2) [Ln = Sm,
      E = Se (6); Ln = Eu, E = Se (7); Ln = Sm, E = Te (9)], whereas reacting the
      Yb(II) bis(amidinate) 5 with PhSeSePh yielded the mononuclear [YbL(2)(SePh)(THF)]
      (8). The reaction of 5 with iodine led to the Yb(III) bis(amidinate) iodide
      complex [YbL(2)(I)(THF)] (10). Treatment of 3 with N,N'-dicyclohexylcarbodiimide
      afforded the mixed-ligand Sm(III) tris(amidinate) [SmL(2){CyNC(H)NCy}] (11) (Cy =
      cyclohexyl). The molecular structures of complexes 2-5 and 7-11 were elucidated
      by X-ray diffraction analyses.

PMID- 19757784
TI  - Single-molecule junctions with strong molecule-electrode coupling.
AB  - We fabricated Au-TTF-Au (tetrathiafulvalene, TTF) and Au-TSF-Au
      (tetraselenafulvalene, TSF) single-molecule junctions using a nanofabricated
      mechanically controllable break junction. We found that Au-TSF-Au and Au-TTF-Au
      single-molecule junctions have one and two stable configurations, respectively,
      and that the Au-TTF-Au single-molecule conductance is larger than that of Au-TSF
      Au. The difference in single-molecule conductances of the two types of junctions
      originates from the difference in the strength of the molecule-electrode coupling
      through face-to-face overlapping configurations.

PMID- 19757785
TI  - Classical collision spectrum of O + CO.
AB  - The work of Noid et al. [ J. Chem. Phys. 1977 , 67 , 404 ] has shown that sharp
      molecular spectra can be obtained through a Fourier transform of the
      autocorrelation function of a classical trajectory. In the present work, we
      extend this idea to obtain a spectrum by Fourier transform of the dipole moment
      function of collision product trajectories. We show that this "classical
      collision spectrum" (CCS) is related to the cross section for creating the
      product times an Einstein A factor. As a test case, we analyze product CO
      trajectories obtained from O + CO collisions at 8 km/s and focus on the spectral
      resolution of the CCS. The CCS of these trajectories shows rich quantum-like
      features, including well-separated vibrational overtones and rotational band
      heads, which become more pronounced with particular trajectory weighting methods.
      For polyatomic cases, the hope is that the CCS can be deconvolved into ro
      vibrational specific probabilities and cross sections for quasi-periodic
      trajectories, which would otherwise overlap in a conventional classical
      trajectory energy analysis. Chaotic trajectories are expected to broaden and
      decrease the achievable resolution of the CCS. Chaotic motion will therefore
      impact the ability to separate ro-vibrational specific cross sections, an issue
      that will be addressed in future work.

PMID- 19757786
TI  - Intramolecular amide stacking and its competition with hydrogen bonding in a
      small foldamer.
AB  - Attractive interactions between two carboxamide groups in a "stacked" geometry
      are explored under isolated molecule conditions. Infrared spectra of single
      conformations of a small gamma-peptide, Ac-gamma(2)-hPhe-NHMe, reveal the
      presence of a conformation in which the two amide planes are approximately
      parallel with the amide dipoles in an antialigned orientation. This stacked
      conformation is energetically comparable to conformations that contain an
      intramolecular amide-amide H-bond. Amide stacking interactions can compete with H
      bonding in circumstances where the amide groups can be brought into a stacking
      configuration with minimal strain, opening the way for its use in the design of
      future foldamer structures.

PMID- 19757787
TI  - Nanoscale friction switches: friction modulation of monomolecular assemblies
      using external electric fields.
AB  - This paper presents experimental investigations to actively modulate the
      nanoscale friction properties of a self-assembled monolayer (SAM) assembly using
      an external electric field that drives conformational changes in the SAM. Such
      "friction switches" have widespread implications in interfacial energy control in
      micro/nanoscale devices. Friction response of a low-density mercaptocarboxylic
      acid SAM is evaluated using an atomic force microscope (AFM) in the presence of a
      DC bias applied between the sample and the AFM probe under a nitrogen (dry)
      environment. The low density allows reorientation of individual SAM molecules to
      accommodate the attractive force between the -COOH terminal group and a
      positively biased surface. This enables the surface to present a hydrophilic
      group or a hydrophobic backbone to the contacting AFM probe depending upon the
      direction of the field (bias). Synthesis and deposition of the low-density SAM
      (LD-SAM) is reported. Results from AFM experiments show an increased friction
      response (up to 300%) of the LD-SAM system in the presence of a positive bias
      compared to the friction response in the presence of a negative bias. The
      difference in the friction response is attributed to the change in the structural
      and crystalline order of the film in addition to the interfacial surface
      chemistry and composition presented upon application of the bias.

PMID- 19757788
TI  - N-heterocyclic carbene-catalyzed generation of alpha,beta-unsaturated acyl
      imidazoliums: synthesis of dihydropyranones by their reaction with enolates.
AB  - Catalytic generation of alpha,beta-unsaturated acyl imidazolium cations and
      enolates has been achieved, and their involvement in a Michael addition acylation
      sequence exploited, to provide a range of dihydropyranones. alpha,beta
      Unsaturated enol esters, or alpha,beta-unsaturated acid fluorides in association
      with TMS enol ethers, serve as appropriate substrates for this reaction. The
      transformation can also be achieved enantioselectively using catalysts derived
      from chiral triazolium salts.

PMID- 19757789
TI  - Efficient and rapid template-directed nucleic acid copying using 2'-amino-2',3'
      dideoxyribonucleoside-5'-phosphorimidazolide monomers.
AB  - The development of a sequence-general nucleic acid copying system is an essential
      step in the assembly of a synthetic protocell, an autonomously replicating
      spatially localized chemical system capable of spontaneous Darwinian evolution.
      Previously described nonenzymatic template-copying experiments have validated the
      concept of nonenzymatic replication, but have not yet achieved robust, sequence
      general polynucleotide replication. The 5'-phosphorimidazolides of the 2'-amino
      2',3'-dideoxyribonucleotides are attractive as potential monomers for such a
      system because they polymerize by forming 2'-->5' linkages, which are favored in
      nonenzymatic polymerization reactions using similarly activated ribonucleotides
      on RNA templates. Furthermore, the 5'-activated 2'-amino nucleotides do not
      cyclize. We recently described the rapid and efficient nonenzymatic copying of a
      DNA homopolymer template (dC(15)) encapsulated within fatty acid vesicles using
      2'-amino-2',3'-dideoxyguanosine-5'-phosphorimidazolide as the activated monomer.
      However, to realize a true Darwinian system, the template-copying chemistry must
      be able to copy most sequences and their complements to allow for the
      transmission of information from generation to generation. Here, we describe the
      copying of a series of nucleic acid templates using 2'-amino-2',3'
      dideoxynucleotide-5'-phosphorimidazolides. Polymerization reactions proceed
      rapidly to completion on short homopolymer RNA and LNA templates, which favor an
      A-type duplex geometry. We show that more efficiently copied sequences are
      generated by replacing the adenine nucleobase with diaminopurine, and uracil with
      C5-(1-propynyl)uracil. Finally, we explore the copying of longer, mixed-sequence
      RNA templates to assess the sequence-general copying ability of 2'-amino-2',3'
      dideoxynucleoside-5'-phosphorimidazolides. Our results are a significant step
      forward in the realization of a self-replicating genetic polymer compatible with
      protocell template copying and suggest that N2'-->P5'-phosphoramidate DNA may
      have the potential to function as a self-replicating system.

PMID- 19757790
TI  - Enzyme-triggered disassembly of dendrimer-based amphiphilic nanocontainers.
AB  - We demonstrate a new enzyme-induced disassembly of amphiphilic nanocontainers
      based on dendrimers. Disassembly and the ensuing release of noncovalently bound
      guest molecules are of great interest because of their implications in areas such
      as drug delivery and sensing. Achieving these with a protein as the stimulus is
      of even greater importance, because proteins are the primary indicators of
      biological imbalances. We achieved disassembly of the nanocontainers by
      disturbing the hydrophilic-lipophilic balance in the amphiphilic dendrimer
      building blocks.

PMID- 19757791
TI  - Relating mechanical properties and chemical bonding in an inorganic-organic
      framework material: a single-crystal nanoindentation study.
AB  - We report the application of nanoindentation and atomic force microscopy to
      establish the fundamental relationships between mechanical properties and
      chemical bonding in a dense inorganic-organic framework material:
      Ce(C(2)O(4))(HCO(2)), 1. Compound 1 is a mixed-ligand 3-D hybrid which
      crystallizes in an orthorhombic space group, in which its three basic building
      blocks, i.e. the inorganic metal-oxygen-metal (M-O-M) chains and the two organic
      bridging ligands, (oxalate and formate) are all oriented perpendicular to one
      another. This unique architecture enabled us to decouple the elastic and plastic
      mechanical responses along the three primary axes of a single crystal to
      understand the contribution associated with stiff vs compliant basic building
      blocks. The (001)-oriented facet that features rigid oxalate ligands down the c
      axis exhibits the highest stiffness and hardness (E approximately 78 GPa and H
      approximately 4.6 GPa). In contrast, the (010)-oriented facet was found to be the
      most compliant and soft (E approximately 43 GPa and H approximately 3.9 GPa),
      since the formate ligand, which is the more compliant building block within this
      framework, constitutes the primary linkages down the b-axis. Notably,
      intermediate stiffness and hardness (E approximately 52 GPa and H approximately
      4.1 GPa) were measured on the (100)-oriented planes. This can be attributed to
      the Ce-O-Ce chains that zigzag down the a-axis (Ce...Ce metal centers form an
      angle of approximately 132 degrees) and also the fact that the 9-coordinated
      CeO(9) polyhedra are expected to be geometrically more compliant. Our results
      present the first conclusive evidence that the crystal orientation dominated by
      inorganic chains is not necessarily more robust from the mechanical properties
      standpoint. Rigid organic bridging ligands (such as oxalate), on the other hand,
      can be used to produce greater stiffness and hardness properties in a chosen
      crystallographic orientation. This study demonstrates that there exists a vast
      opportunity to design the mechanical properties of dense hybrid framework
      materials through the incorporation of organic multifunctional ligands of varying
      rigidity.

PMID- 19757792
TI  - All-polymer photovoltaic devices of poly(3-(4-n-octyl)-phenylthiophene) from
      Grignard Metathesis (GRIM) polymerization.
AB  - The synthesis of poly[3-(4-n-octyl)-phenylthiophene] (POPT) from Grignard
      Metathesis (GRIM) is reported. GRIM POPT is found to have favorable electronic,
      optical, and processing properties for organic photovoltaics (OPVs). Space-charge
      limited current and field effect transistor measurements for POPT yielded hole
      mobilities of 1 x 10(-4) cm(2)/(V s) and 0.05 cm(2)/(V s), respectively.
      Spincasting GRIM POPT from chlorobenzene yields a thin film with a 1.8 eV band
      gap, and PC(61)BM:POPT bulk heterojection devices provide a peak performance of
      3.1%. Additionally, an efficiency of 2.0% is achieved in an all-polymer, bilayer
      OPV using poly[2-methoxy-5-(2'-ethylhexyloxy)-1,4-(1-cyanovinylene)phenylene]
      (CNPPV) as an acceptor. This state-of-the-art all-polymer device is analyzed in
      comparison to the analogous poly(3-hexylthiophene) (P3HT)/CNPPV device. Counter
      to expectations based on more favorable energy level alignment, greater active
      layer light absorption, and similar hole mobility, P3HT/CNPPV devices perform
      less well than POPT/CNPPV devices with a peak efficiency of 0.93%.

PMID- 19757793
TI  - Well-defined Ir/Pd complexes with a triazolyl-diylidene bridge as catalysts for
      multiple tandem reactions.
AB  - The ligand 1,2,4-trimethyl-triazolyl-diylidene has been used for the preparation
      of a series of three iridium/palladium heterometallic complexes that have been
      fully characterized. The presence of the two different metals allows tandem
      processes to be designed by combining reactions that are typically catalyzed by
      Ir and Pd. Three tandem reactions have been studied: dehalogenation/transfer
      hydrogenation of haloacetophenones, Suzuki-coupling/transfer hydrogenation of p
      bromoacetophenone, and Suzuki-coupling/alpha-alkylation of p-bromoacetophenone.
      All three reactions yielded excellent outcomes to the corresponding final
      products, with the relevant feature that the heterodimetallic complexes are more
      active than the sum of the corresponding homodimetallic species. All three
      catalytic reactions reported here constitute unprecedented examples of tandem
      approaches to complex organic molecules.

PMID- 19757794
TI  - Ion/ion reactions: new chemistry for analytical MS.
AB  - Gas-phase ion/ion reactions are emerging as flexible means for probing and
      manipulating analyte ions with particular utility in bioanalysis.

PMID- 19757795
TI  - Modeling the syn disposition of nitrogen donors in non-heme diiron enzymes.
      Synthesis, characterization, and hydrogen peroxide reactivity of diiron(III)
      complexes with the syn N-donor ligand H2BPG2DEV.
AB  - In order to model the syn disposition of histidine residues in carboxylate
      bridged non-heme diiron enzymes, we prepared a new dinucleating ligand,
      H(2)BPG(2)DEV, that provides this geometric feature. The ligand incorporates
      biologically relevant carboxylate functionalities, which have not been explored
      as extensively as nitrogen-only analogues. Three novel oxo-bridged diiron(III)
      complexes, [Fe(2)(mu-O)(H(2)O)(2)(BPG(2)DEV)](ClO(4))(2) (6), [Fe(2)(mu-O)(mu
      O(2)CAr(iPrO))(BPG(2)DEV)](ClO(4)) (7), and [Fe(2)(mu-O)(mu-CO(3))(BPG(2)DEV)]
      (8), were prepared. Single-crystal X-ray structural characterization confirms
      that two pyridyl groups are bound syn with respect to the Fe-Fe vector in these
      compounds. The carbonato-bridged complex 8 forms quantitatively from 6 in a rapid
      reaction with gaseous CO(2) in organic solvents. A common maroon-colored
      intermediate (lambda(max) = 490 nm; epsilon = 1500 M(-1) cm(-1)) forms in
      reactions of 6, 7, or 8 with H(2)O(2) and NEt(3) in CH(3)CN/H(2)O solutions. Mass
      spectrometric analyses of this species, formed using (18)O-labeled H(2)O(2),
      indicate the presence of a peroxide ligand bound to the oxo-bridged diiron(III)
      center. The Mossbauer spectrum at 90 K of the EPR-silent intermediate exhibits a
      quadrupole doublet with delta = 0.58 mm/s and DeltaE(Q) = 0.58 mm/s. The isomer
      shift is typical for a peroxodiiron(III) species, but the quadrupole splitting
      parameter is unusually small compared to those of related complexes. These
      Mossbauer parameters are comparable to those observed for a peroxo intermediate
      formed in the reaction of reduced toluene/o-xylene monooxygenase hydroxylase with
      dioxygen. Resonance Raman studies reveal an unusually low-energy O-O stretching
      mode in the peroxo intermediate that is consistent with a short diiron distance.
      Although peroxodiiron(III) intermediates generated from 6, 7, and 8 are poor O
      atom-transfer catalysts, they display highly efficient catalase activity, with
      turnover numbers up to 10,000. In contrast to hydrogen peroxide reactions of
      diiron(III) complexes that lack a dinucleating ligand, the intermediates
      generated here could be re-formed in significant quantities after a second
      addition of H(2)O(2), as observed spectroscopically and by mass spectrometry.

PMID- 19757796
TI  - Chunganenol: an unusual antioxidative resveratrol hexamer from Vitis
      chunganensis.
AB  - Chunganenol (1), an unusual resveratrol hexamer, has been isolated from Vitis
      chunganensis. Its unprecedented structure has been assigned through detailed
      analyses of 2D NMR data and consideration of oligostilbene biosynthetic pathway,
      representing the first highly condensed stilbene oligomer from Vitaceous plants.
      It also featured a novel interunit lingkage where two stilbene units are
      connected by a methylene bridge. Moreover, 1 exhibited potent and selective
      quenching effects on singlet oxygen, and might play a role in the antioxidative
      defense system of the plant.

PMID- 19757797
TI  - Quantitative analyses of mixtures of 2-deuterio-1-vinylcyclobutanes.
AB  - Making distinctions between two stereoisomers characterized by diastereotopic
      deuterium atoms can ordinarily be achieved using standard NMR spectroscopic
      methods. Mixtures of stereoisomers having both diastereotopic and enantiotopic
      deuterium labels, however, may be difficult to analyze quantitatively. The
      present work introduces a simple way to gain quantitative analyses of mixtures of
      the four stereoisomeric 2-deuterio-1-vinylcyclobutanes, an essential prerequisite
      to establishing the stereochemical characteristics of the thermal stereomutations
      of vinylcyclobutane and its structural isomerizations to cyclohexene. The
      unconventional NMR method introduced and validated in this work will likely prove
      convenient and generally applicable to related stereochemical investigations.

PMID- 19757798
TI  - Fullerene/thiol-terminated molecules.
AB  - A series of fullerene-terminated oligo(phenylene ethynylene) (OPEs) have been
      synthesized for potential use in electronic or optoelectronic device monolayers.
      Electronic properties such as the energy levels and the distribution of HOMOs and
      LUMOs of fullerene-terminated OPEs have been calculated using the ab initio
      method at the B3LYP/6-31G(d) level. The calculations have revealed the
      concentration of frontier orbitals on the fullerene cage and a narrow
      distribution of HOMO-LUMO energy gaps. Ultraviolet photoelectron spectroscopy and
      inverse photoemission spectroscopy studies have been performed to further examine
      the electronic properties of the fullerene-terminated OPEs on gold surfaces. The
      obtained broad photoelectron spectra suggest that there are strong intermolecular
      interactions in the fullerene self-assembled monolayers, and the small bandgap
      (approximately 1.5 eV), determined by the photoelectron spectroscopy, indicates
      the unique nature of the fullerene-terminated OPEs in which the C(60) moiety can
      be connected to the Au surface through the conjugated OPE backbone.

PMID- 19757799
TI  - Protein tertiary structural changes visualized by time-resolved X-ray solution
      scattering.
AB  - We obtained a solution structural model of myoglobin (Mb) formed upon the CO
      photolysis of MbCO by analyzing time-resolved X-ray solution scattering data. An
      experiment-restrained rigid-body molecular dynamics simulation was used to find
      the best model whose theoretical difference scattering curve gives a satisfactory
      agreement with the experimental data at the time delay of 10 ns. The obtained
      solution model shows structural changes similar to crystallographic models for
      MbCO --> Mb but also displays a noticeable difference in that the N-terminus and
      F helix show larger structural changes.

PMID- 19757800
TI  - Ultrahigh-performance inverters based on CdS nanobelts.
AB  - We report ultrahigh-performance inverters, each consisting of two top-gate metal
      oxide-semiconductor field-effect transistors based on n-CdS nanobelts. High-kappa
      HfO(2) dielectrics are used as the top-gate oxide layers. The inverters have a
      large supply voltage (V(DD)) range (from 50 mV to 10 V) and very high voltage
      gain ( approximately 10, 100, and 1000 at V(DD) = 0.2, 1, and 10 V,
      respectively). Current consumption is less than 7 nA at V(DD) = 1 V,
      corresponding to a power consumption of less than 7 nW. The high and low output
      voltages are close to full rail. The inverters also exhibit good dynamic behavior
      with square wave input at frequencies up to 1 kHz. The operation of the inverters
      is analyzed in detail. The inverters are promising for future low power high
      performance logic circuit applications.

PMID- 19757801
TI  - Direct enantioselective organocatalytic hydroxymethylation of aldehydes catalyzed
      by alpha,alpha-diphenylprolinol trimethylsilyl ether.
AB  - The direct enantioselective hydroxymethylation of aldehydes utilizing alpha,alpha
      diphenylprolinol trimethylsilyl ether as an organocatalyst is described. The
      intermediate alpha-substituted beta-hydroxyaldehydes were not isolated but
      converted to the more readily isolable derivatives. For example, the derived
      hydroxy acids were isolated in up to 94% yield with excellent enantioselectivity.

PMID- 19757802
TI  - Solid-phase peptide synthesis in water using microwave-assisted heating.
AB  - An approach using water as a solvent (coupling and deprotection) was developed
      for the solid-phase synthesis of peptides using the most common Boc-amino acid
      derivatives. Key aspects of this methodology are the use of a PEG-based resin,
      EDC-HONB as a coupling method, and microwave irradiation as an energy source.

PMID- 19757803
TI  - Structure determination of two modulated gamma-brass structures in the Zn-Pd
      System through a (3 + 1)-dimensional space description.
AB  - The structure determination of two composite compounds in the Zn-Pd system with
      close relationships to the cubic gamma-brass structure Zn(11-delta)Pd(2+delta) is
      reported. Their structures have been solved from single crystal X-ray diffraction
      data within a (3 + 1)-dimensional [(3 + 1)D] formalism. Zn(75.7(7))Pd(24.3) and
      Zn(78.8(7))Pd(21.2) crystallize with orthorhombic symmetry, superspace group
      Xmmm(00gamma)0s0 (X = [(1/2,1/2,0,0); (0,1/2,1/2,1/2); (1/2,0,1/2,1/2)]), with
      the following lattice parameters, respectively: a(s) = 12.929(3) A, b(s) =
      9.112(4) A, c(s) = 2.5631(7) A, q = 8/13 c* and V(s) = 302.1(3) A(3) and a(s) =
      12.909(3) A, b(s) = 9.115(3) A, c(s) = 2.6052(6) A, q = 11/18 c* and V(s) =
      306.4(2) A(3). Their structures may be considered as commensurate because they
      can be refined in the conventional 3D space groups (Cmce and Cmcm, respectively)
      using supercells, but they also refined within the (3 + 1)D formalism to residual
      factors R = 3.14% for 139 parameters and 1184 independent reflections for
      Zn(75.7(7))Pd(24.3) and R = 3.16% for 175 parameters and 1804 independent
      reflections for Zn(78.8(7))Pd(21.2). The use of the (3 + 1)D formalism improves
      the results of the refinement and leads to a better understanding of the
      complexity of the atomic arrangement through the various modulations (occupation
      waves and displacive waves). Our refinements emphasize a unique Pd/Zn occupancy
      modulation at the center of distorted icosahedra, a modulation which correlates
      with the distortion of these polyhedra.

PMID- 19757804
TI  - Matrix-isolation and Ab initio study of the HKrCl...HCl complex.
AB  - The HKrCl complex with HCl is characterized by IR spectroscopy in a Kr matrix and
      by ab initio calculations. The HKrCl...HCl complex exhibits a strong blue shift
      of the H-Kr stretching mode in comparison with the HKrCl monomer, which indicates
      stabilization of the H-Kr bond upon complexation. The obtained maximal shift of
      ca. +300 cm(-1) is probably the largest blue shift experimentally observed for
      1:1 molecular complexes. The HCl absorptions are found to be strongly red-shifted
      upon complexation with HKrCl (up to ca. -500 cm(-1)). In the HKrCl synthesis
      procedure, an HCl/Kr matrix was first photolyzed at 193 nm to yield H and Cl
      atoms in a Kr matrix and then annealed at about 30 K to activate mobility of H
      atoms and to promote the H + Kr + Cl reaction. The HKrCl...HCl complex is mainly
      formed from the Cl...HCl intermediate complex that is produced by photolysis of
      HCl dimers. Bands of the HKrCl...(HCl)(2) complex are tentatively identified with
      a very large shift of ca. +700 cm(-1) for the H-Kr stretching mode. These
      experimental observations are supported and explained by ab initio calculations.

PMID- 19757805
TI  - Biomimetic and microbial approaches to solar fuel generation.
AB  - Photosynthesis is performed by a multitude of organisms, but in nearly all cases,
      it is variations on a common theme: absorption of light followed by energy
      transfer to a reaction center where charge separation takes place. This initial
      form of chemical energy is stabilized by the biosynthesis of carbohydrates. To
      produce these energy-rich products, a substrate is needed that feeds in reductive
      equivalents. When photosynthetic microorganisms learned to use water as a
      substrate some 2 billion years ago, a fundamental barrier against unlimited use
      of solar energy was overcome. The possibility of solar energy use has inspired
      researchers to construct artificial photosynthetic systems that show analogy to
      parts of the intricate molecular machinery of photosynthesis. Recent years have
      seen a reorientation of efforts toward creating integrated light-to-fuel systems
      that can use solar energy for direct synthesis of energy-rich compounds, so
      called solar fuels. Sustainable production of solar fuels is a long awaited
      development that promises extensive solar energy use combined with long-term
      storage. The stoichiometry of water splitting into molecular oxygen, protons, and
      electrons is deceptively simple; achieving it by chemical catalysis has proven
      remarkably difficult. The reaction center Photosystem II couples light-induced
      charge separation to an efficient molecular water-splitting catalyst, a Mn(4)Ca
      complex, and is thus an important template for biomimetic chemistry. In our aims
      to design biomimetic manganese complexes for light-driven water oxidation, we
      link photosensitizers and charge-separation motifs to potential catalysts in
      supramolecular assemblies. In photosynthesis, production of carbohydrates demands
      the delivery of multiple reducing equivalents to CO(2). In contrast, the two
      electron reduction of protons to molecular hydrogen is much less demanding.
      Virtually all microorganisms have enzymes called hydrogenases that convert
      protons to hydrogen, many of them with good catalytic efficiency. The catalytic
      sites of hydrogenases are now the center of attention of biomimetic efforts,
      providing prospects for catalytic hydrogen production with inexpensive metals.
      Thus, we might complete the water-to-fuel conversion: light + 2H(2)O --> 2H(2) +
      O(2). This reaction formula is to some extent already elegantly fulfilled by
      cyanobacteria and green algae, water-splitting photosynthetic microorganisms that
      under certain conditions also can produce hydrogen. An alternative route to
      hydrogen from solar energy is therefore to engineer these organisms to produce
      hydrogen more efficiently. This Account describes our original approach to
      combine research in these two fields: mimicking structural and functional
      principles of both Photosystem II and hydrogenases by synthetic chemistry and
      engineering cyanobacteria to become better hydrogen producers and ultimately
      developing new routes toward synthetic biology.

PMID- 19757806
TI  - Quartz crystal microbalance studies of Al2O3 atomic layer deposition using
      trimethylaluminum and water at 125 degrees C.
AB  - Al(2)O(3) atomic layer deposition (ALD) growth with Al(CH(3))(3)
      (trimethylaluminum (TMA)) and H(2)O as the reactants was examined at the
      relatively low temperature of 125 degrees C using quartz crystal microbalance
      (QCM) measurements. The total Al(2)O(3) ALD mass gain per cycle (MGPC) and MGPCs
      during the individual TMA and H(2)O reactions were measured versus TMA and H(2)O
      exposures. The Al(2)O(3) MGPC increased with increasing H(2)O and TMA exposures
      at fixed TMA and H(2)O exposures, respectively. However, the TMA and H(2)O
      reactions were not completely self-limiting. The slower surface reaction kinetics
      at lower temperature may require very long exposures for the reactions to reach
      completion. The Al(2)O(3) MGPCs increased quickly versus H(2)O exposure and
      slowly reached limiting values that were only weakly dependent on the TMA doses.
      Small TMA exposures were also sufficient for the Al(2)O(3) MGPCs to reach
      different limiting values for different H(2)O doses. The TMA MGPCs increased for
      higher TMA exposures at all H(2)O exposures. In contrast, the H(2)O MGPCs
      decreased for higher TMA exposures at all H(2)O exposures. This decrease may
      occur from more dehydroxylation at larger hydroxyl coverages after the H(2)O
      exposures. The hydroxyl coverage after the H(2)O exposure was dependent only on
      the H(2)O exposure. The Al(2)O(3) MGPC was also linearly dependent on the
      hydroxyl coverage after the H(2)O dose. Both the observed hydroxyl coverage
      versus H(2)O exposure and the Al(2)O(3) ALD growth versus H(2)O and TMA exposures
      were fit using modified Langmuir adsorption isotherm expressions where the
      pressures are replaced with exposures. These results should be useful for
      understanding low-temperature Al(2)O(3) ALD, which is important for coating
      organic, polymeric, and biological substrates.

PMID- 19757807
TI  - Ionic liquids and their interaction with cellulose.

PMID- 19757808
TI  - Chain-growth condensation polymerization for the synthesis of well-defined
      condensation polymers and pi-conjugated polymers.

PMID- 19757809
TI  - Enabling cleaner fuels: desulfurization by adsorption to microporous coordination
      polymers.
AB  - Microporous coordination polymers (MCPs) are demonstrated to be efficient
      adsorbents for the removal of the organosulfur compounds dibenzothiophene (DBT)
      and 4,6-dimethyldibenzothiophene (DMDBT) from model diesel fuel and diesel fuel.
      For example, packed bed breakthrough experiments utilizing UMCM-150 find
      capacities of 25.1 g S/kg MCP for DBT and 24.3 g S/kg MCP for DMDBT from
      authentic diesel indicating that large amounts of fuel are desulfurized before
      the breakthrough point. Unlike activated carbons, where selectivity has been a
      problem, MCPs selectively adsorb the organosulfur compounds over other, similar
      components of diesel. Complete regeneration using toluene at modest temperatures
      is achieved. The attainment of high selectivities and capacities, particularly
      for the adsorption of the refractory compounds that are difficult to remove using
      current desulfurization techniques, in a reversible sorbent indicates that fuel
      desulfurization may be an important application for MCPs.

PMID- 19757810
TI  - An unsymmetric oxo/imido-bridged germanium-centered singlet diradicaloid.
AB  - Reaction of the digermyne Ar'GeGeAr' (1) with ONC(6)H(4)-2-CH(3) affords a unique
      example of an unsymmetric singlet diradicaloid, the oxo/imido-bridged species
      Ar'Ge(mu-O)(mu-NC(6)H(4)-2-CH(3))GeAr' (2), which was characterized by
      spectroscopy, X-ray crystallography, and density functional theory computations.
      The direct reaction of 1 with O(2) to generate the symmetric diradicaloid
      Ar'Ge(mu(2)-O)(2)GeAr' led to the double-addition product Ar'Ge(mu(2)
      O)(2)(eta(1),eta(1):mu(2)-O(2))GeAr' (8), which was also characterized
      structurally and spectroscopically. Calculations on simple models showed that the
      HOMO-LUMO energy gap decreases as the imido bridges in MeGe(mu-NH)(2)GeMe are
      replaced by oxygens, which is consistent with the higher reactivity of
      Ar'Ge(mu(2)-O)(2)GeAr' toward further O(2) addition.

PMID- 19757811
TI  - Evaluation of an oral carrier system in rats: bioavailability and antioxidant
      properties of liposome-encapsulated curcumin.
AB  - To enhance the curcumin absorption by oral administration, liposome-encapsulated
      curcumin (LEC) was prepared from commercially available lecithins (SLP-WHITE and
      SLP-PC70) and examined for its interfacial and biochemical properties. A LEC
      prepared from 5 wt % of SLP-PC70 and 2.5 wt % of curcumin gave a good
      dispersibility with 68.0% encapsulation efficiency for curcumin, while those from
      SLP-WHITE did not. Moreover, the resulting LEC using SLP-PC70 was confirmed to be
      composed of small unilamellar vesicles with a diameter of approximately 263 nm.
      The resulting LEC was then examined for its effect on bioavailability in Sprague
      Dawley (SD) rats. Three forms of curcumin [curcumin, a mixture of curcumin and
      SLP-PC70 (lecithin), and LEC] were then administered orally to SD rats at a dose
      of 100 mg curcumin/kg body weight. The pharmacokinetic parameters following
      curcumin administration were determined in each form. Pharmacokinetic parameters
      after oral administration of LEC were compared to those of curcumin and a mixture
      of curcumin and lecithin. High bioavailability of curcumin was evident in the
      case of oral LEC; a faster rate and better absorption of curcumin were observed
      as compared to the other forms. Oral LEC gave higher C(max) and shorter T(max)
      values, as well as a higher value for the area under the blood concentration-time
      curve, at all time points. These results indicated that curcumin enhanced the
      gastrointestinal absorption by liposomes encapsulation. Interestingly, the plasma
      antioxidant activity following oral LEC was significantly higher than that of the
      other treatments. In addition, the plasma curcumin concentration was
      significantly correlated to plasma antioxidant activities, and enhanced curcumin
      plasma concentrations might exert a stronger influence on food functionality of
      curcumin. The available information strongly suggests that liposome encapsulation
      of ingredients such as curcumin may be used as a novel nutrient delivery system.

PMID- 19757812
TI  - Synthesis, stability, and photochemistry of pentacene, hexacene, and heptacene: a
      matrix isolation study.
AB  - The photochemical bisdecarbonylation of bridged alpha-diketones (Strating
      Zwanenburg reaction) to give the oligoacenes pentacene (2), hexacene (3), and
      heptacene (4) is investigated in solid inert gas matrices at cryogenic
      temperatures. The photodecomposition using visible light irradiation cleanly
      produces the corresponding oligoacene without formation of observable
      intermediates. This synthetic approach to the higher acenes allows a
      comprehensive comparative study of their electronic absorption and infrared
      spectral properties under identical conditions for the first time. In addition,
      the route makes it possible to investigate the thermal and photochemical
      stability of these higher acenes and addresses the problem of heptacene stability
      which dates back almost 70 years. This largest known member of the acene series
      is found to be unstable at room temperature. Furthermore, all oligoacenes 2-4
      undergo a photoredox reaction upon 185 nm excitation, resulting in the concurrent
      formation of radical cations and anions in the noble gas matrix. These polaron
      states of the oligoacenes are stable under the conditions of their generation but
      collapse to the uncharged acenes upon visible light irradiation.

PMID- 19757813
TI  - Effects of ultraviolet irradiation on the physicochemical and functional
      properties of gum arabic.
AB  - The impact of ultraviolet (UV) irradiation on the physicochemical and functional
      properties of gum arabic was investigated. Gum arabic samples were exposed to UV
      irradiation for 30, 60, 90, and 120 min; gum arabic was also treated with
      formaldehyde for comparison. Molecular weight analysis using gel permeation
      chromatography indicated that no significant changes occurred on the molecular
      structure on the samples exposed to UV irradiation. Free amino group analysis
      indicated that mild UV irradiation (30 min) could induce cross-linking on gum
      arabic; this result was comparable with that of samples treated with
      formaldehyde. However, viscosity break down was observed for samples exposed to
      UV irradiation for longer times (90 and 120 min). All irradiated and formaldehyde
      treated samples exhibited better emulsification properties than unirradiated
      samples. These results indicate that UV-irradiated gum arabic could be a better
      emulsifier than the native (unmodified) gum arabic and could be exploited
      commercially.

PMID- 19757814
TI  - Heterolytic cleavage of disulfides by frustrated Lewis pairs.
AB  - The addition of diphenyl disulfide (PhSSPh) to tBu(2)P(C(6)F(4))B(C(6)F(5))(2)
      (1) affords the zwitterionic phosphonium borate
      [tBu(2)P(SPh)(C(6)F(4))B(SPh)(C(6)F(5))(2)] (2), while the addition of a base or
      donor solvent to 2 effected the liberation of disulfide and the formation of
      [tBu(2)P(C(6)F(4))B(donor)(C(6)F(5))(2)]. The reaction of 1 with S(8) gave
      tBu(2)P(S)(C(6)F(4))B(C(6)F(5))(2) (3). In a similar fashion, the frustrated
      Lewis pair of tBu(3)P/B(C(6)F(5))(3) reacts with RSSR to give
      [tBu(3)P(SR)][(RS)B(C(6)F(5))(3)] (R = Ph (4), p-tolyl (5), iPr (6)). In
      contrast, the corresponding reaction of BnSSBn yields a 1:1:1 mixture of tBu(3)P
      horizontal lineS, Bn(2)S, and B(C(6)F(5))(3). Species 4 reacts with p-tolylSSp
      tolyl to give a mixture of 4, 5, PhSSPh, and p-tolylSS p-tolyl, while treatment
      of 5 with PhSSPh afforded a similar mixture. To probe this, a crossover
      experiment between [tBu(3)P(SPh)][B(C(6)F(5))(4)] (7) and [NBu(4)][(p
      tolylS)B(C(6)F(5))(3)] (9) was performed. The former species was prepared by a
      reaction of 4 with [Ph(3)C][B(C(6)F(5)) (4)], while cation exchange of
      [(Et(2)O)(2)Li( p-tolylS)B(C(6)F(5))(3)] (8) with [NBu(4)]Br gave 9. The reaction
      of compounds 7 and 9 gave a statistical mixture of the cations [tBu(3)P(SR)](+)
      and anions [(RS)B(C(6)F(5))(3)](-), R = Ph, Sp-tolyl. The mechanism of this
      exchange process was probed and is proposed to be an equilibrium involving
      disulfide and the frustrated Lewis pair. Crystallographic data are reported for
      compounds 4-8, and the natures of the P-S cations are examined via DFT
      calculations.

PMID- 19757815
TI  - Synthesis, biological evaluation, and structure-activity relationships for 5-[(E)
      2-arylethenyl]-3-isoxazolecarboxylic acid alkyl ester derivatives as valuable
      antitubercular chemotypes.
AB  - Tuberculosis (TB), mostly caused by Mycobacterium tuberculosis (Mtb), is one of
      the leading causes of death from infectious disease worldwide. Its coinfection
      with HIV and the emergence of multidrug-resistant TB (MDR-TB) and extensively
      drug-resistant TB (XDR-TB) strains have further worsened the TB pandemic. Despite
      its global impact, TB is considered a neglected disease and no new anti-TB
      therapeutics have been introduced over the last four decades. The nonreplicating
      persistent form of TB (NRP-TB) is responsible for the length of the treatment and
      is the putative cause of treatment failure. Therefore, new anti-TB agents, which
      are active against both the replicating form of Mtb (R-TB) and NRP-TB, are
      urgently needed. Herein, we report the synthesis and structure-activity
      relationships (SAR) of a series of 5-[(E)-2-arylethenyl]-3-isoxazolecarboxylic
      acid alkyl esters as potent anti-TB agents. Several compounds had submicromolar
      minimum inhibitory concentrations (MIC) against R-TB and were active against NRP
      TB in the low micromolar range, thus representing attractive lead compounds for
      the possible development of new anti-TB agents.

PMID- 19757816
TI  - New insights on CO2-methane separation using LTA zeolites with different Si/Al
      ratios and a first comparison with MOFs.
AB  - LTA zeolites can be synthesized with tailored adsorption properties by
      controlling the Al content in the framework. In this work, we have demonstrated
      that it is possible to adjust the polarity of the zeolitic adsorbent to optimize
      its thermodynamic adsorption properties for the energetically relevant
      CO(2)/CH(4) separation process. The thermodynamic study has been made from the
      corresponding adsorption isotherms of the pure gases carried out at different
      pressures and temperatures, as well as breakthrough separation experiments of
      CO(2)/CH(4) mixtures and the results were compared to those reported on MOFs. The
      separation values obtained allow us to conclude that LTA zeolites offer unique
      possibilities for CH(4) upgrading from natural gas.

PMID- 19757817
TI  - Silver cluster formation, dynamics, and chemistry in metal-organic frameworks.
AB  - Synthetic methods used to produce metal nanoparticles typically lead to a
      distribution of particle sizes. In addition, creation of the smallest clusters,
      with sizes of a few to tens of atoms, remains very challenging. Nanoporous metal
      organic frameworks (MOFs) are a promising solution to these problems, since their
      long-range crystalline order creates completely uniform pore sizes with the
      potential for both steric and chemical stabilization. We report a systematic
      investigation of silver nanocluster formation within MOFs using three
      representative MOF templates. The as-synthesized clusters are spectroscopically
      consistent with dimensions < or =1 nm, with a significant fraction existing as
      Ag(3) clusters, as shown by electron paramagnetic resonance. Importantly, we show
      conclusively that very rapid TEM-induced MOF degradation leads to agglomeration
      and stable, easily imaged particles, explaining prior reports of particles larger
      than MOF pores. These results solve an important riddle concerning MOF-based
      templates and suggest that heterostructures composed of highly uniform arrays of
      nanoparticles within MOFs are feasible.

PMID- 19757818
TI  - Synthesis of surfactants based on pentaerythritol. I. Cationic and zwitterionic
      gemini surfactants.
AB  - Simple strategies for the synthesis of five series of cationic gemini surfactants
      and one series of zwitterionic gemini surfactants from pentaerythritol have been
      developed. Two lipophilic groups were introduced onto pentaerythritol by
      alkylation of the known compound, O-benzylidenepentaerythritol, with 1
      bromooctane, 1-bromodecane, 1-bromododecane, and 1-bromotetradecane.
      Hydrogenolysis of the benzylidene acetals gave diols which were converted into
      three different series of trimethylammonium derivatives. The diiodides derived
      from the diols could be displaced by dimethylamine, even though they are adjacent
      to a quaternary carbon atom. Alkylation with methyl iodide gave the first series.
      The iodides were easily displaced by cyanide ion and the resulting dinitriles
      were hydrolyzed, converted to N,N-dimethylamides, and reduced to give a second
      series. Oxidation of the diols to dialdehydes under Swern conditions followed by
      Horner-Wadsworth-Emmons reactions with diethyl N,N
      dimethylcarbamoylmethylphosphonate followed by two-stage reduction gave a third
      series. The dialkoxides derived from the four di-O-alkylpentaerthritol diols were
      reacted with 2-dimethylaminoethyl chloride and 3-dimethylaminopropyl chloride in
      neighboring-group assisted double Williamson ether syntheses to give precursors
      to two more series. As expected because the neighboring group participation
      occurs through a four-membered-ring intermediate, considerably more vigorous
      conditions were required for the reactions with 3-dimethylaminopropyl chloride. 2
      Diethylaminoethyl bromide was found to be less reactive than 2-dimethylaminoethyl
      chloride. The products were alkylated with methyl iodide and, in some cases,
      other alkyl halides to give cationic gemini surfactants. Alkylation of one series
      with ethyl bromoacetate followed by anion exchange resin catalyzed ester
      hydrolysis gave zwitterionic gemini surfactants. The members of all series have
      superior surfactant properties.

PMID- 19757820
TI  - Synthesis of silver nanoparticles coated with OH-functionalized organic groups:
      dispersion and covalent bonding in epoxy networks.
AB  - The introduction of reactive functionalities in the organic groups used to
      stabilize inorganic nanoparticles (NPs) enables multiple applications based on
      their covalent fixation to a variety of materials, substrates and interfaces. In
      this paper we report the synthesis of silver nanoparticles (NPs) with an average
      diameter of about 4 nm, coated with particular organic groups that allow their
      solubility in a variety of organic solvents and the covalent bonding through
      secondary hydroxyl groups present in their structure. Water-dispersible NPs
      stabilized with 11-mercaptoundecanoate anions were first synthesized. The
      esterification of carboxylate groups with phenyl glycidyl ether generated 2
      hydroxyester functionalities and made the NPs dispersible in a variety of organic
      solvents. To illustrate the multiple possible applications of the synthesized
      NPs, their incorporation to an epoxy network is discussed. A solution of the
      silver NPs in diglycidyl ether of bisphenol A was polymerized in the presence of
      benzyldimethylamine as initiator. This led to an epoxy network containing a
      homogeneous dispersion of silver NPs as revealed by the constancy of the plasmon
      band location. Covalent bonding of the NPs to the epoxy matrix was produced by
      chain transfer reactions involving the hydroxyl groups. Nanocomposites were
      strongly colored and exhibited a dependence of the glass transition temperature
      on the concentration of NPs. Several applications are envisaged for these
      materials.

PMID- 19757819
TI  - An overview of chemical processes that damage cellular DNA: spontaneous
      hydrolysis, alkylation, and reactions with radicals.
AB  - The sequence of heterocyclic bases on the interior of the DNA double helix
      constitutes the genetic code that drives the operation of all living organisms.
      With this said, it is not surprising that chemical modification of cellular DNA
      can have profound biological consequences. Therefore, the organic chemistry of
      DNA damage is fundamentally important to diverse fields including medicinal
      chemistry, toxicology, and biotechnology. This review is designed to provide a
      brief overview of the common types of chemical reactions that lead to DNA damage
      under physiological conditions.

PMID- 19757821
TI  - Mechanistic insight into the inhibition of matrix metalloproteinases by platinum
      substrates.
AB  - Platinum compounds are among the most used DNA-damaging anticancer drugs, however
      they can also be tailored to target biological substrates different from DNA, for
      instance enzymes involved in cancer progression. We recently reported that some
      platinum complexes with three labile ligands inhibit matrix metalloproteinase
      activity in a selective way. We have now extended the investigation to a series
      of platinum complexes having three chlorido or one chlorido and a
      dimethylmalonato leaving ligands. All compounds are strong inhibitors of MMP-3 by
      a noncompetitive mechanism, while platinum drugs in clinical use are not.
      Structural investigations reveal that the platinum substrate only loses two
      labile ligands, which are replaced by an imidazole nitrogen of His224 and a
      hydroxyl group, while it retains one chlorido ligand. A chlorido and a hydroxyl
      group are also present in the zinc complex inhibitor of carboxypeptidase A, whose
      active site has strong analogies with that of MMP-3.

PMID- 19757822
TI  - Fluoro-pegylated chalcones as positron emission tomography probes for in vivo
      imaging of beta-amyloid plaques in Alzheimer's disease.
AB  - This paper describes the synthesis and biological evaluation of fluoro-pegylated
      (FPEG) chalcones for the imaging of beta-amyloid (Abeta) plaques in patients with
      Alzheimer's disease (AD). FPEG chalcone derivatives were prepared by the aldol
      condensation reaction. In binding experiments conducted in vitro using Abeta(1
      42) aggregates, the FPEG chalcone derivatives having a dimethylamino group showed
      higher Ki values (20-50 nM) than those having a monomethylamino or a primary
      amine group. When the biodistribution of 11C-labeled FPEG chalcone derivatives
      having a dimethyamino group was examined in normal mice, all four derivatives
      were found to display sufficient uptake for imaging Abeta plaques in the brain.
      18F-labeled 7c also showed good uptake by and clearance from the brain, although
      a slight difference between the 11C and 18F tracers was observed. When the
      labeling of Abeta plaques was carried out using brain sections of AD model mice
      and an AD patient, the FPEG chalcone derivative 7c intensely labeled Abeta
      plaques. Taken together, the results suggest 7c to be a useful candidate PET
      tracer for detecting Abeta plaques in the brain of patients with AD.

PMID- 19757824
TI  - Determination of molecular structure of bisphenylene homologues of BINOL-based
      phosphoramidites by chiroptical methods.
AB  - Vibrational (VCD), electronic circular dichroism (ECD), and IR absorption spectra
      together with transparent spectral region optical rotation (OR) of two
      derivatives of bisphenylene 1,1'-binaphthyl-based phosphoramidites containing
      three stereogenic axes were measured and the results were compared with simulated
      data obtained by ab initio calculations with density functional theory. An
      excellent agreement between experimental and predicted B3LYP/6-31G** and BPW91/6
      31G** VCD spectra enabled the assignment of all VCD bands in the experimental
      spectra, while the Gibbs free energy of all the conformers allowed the
      determination of their relative populations. The calculation of ECD spectra
      showed that CAM-B3LYP/6-311G** provided results superior to those of B3LYP/6
      311G**. The theoretical results for the OR at the B3LYP/6-311G** and CAM-B3LYP/6
      311G** levels were in good agreement with experimental optical rotations, but
      exhibited lower sensitivity in determining particular conformers than VCD and
      ECD. By a careful comparison of experimental VCD, IR, and ECD spectra and OR with
      calculated data, it was possible to assign the absolute configuration of all
      three stereogenic axes and to determine the molecular structure of the studied
      bisphenylene 1,1'-binaphthyl-based phosphoramidites in solution with a high
      degree of confidence.

PMID- 19757823
TI  - Aminoimidazoles as potent and selective human beta-secretase (BACE1) inhibitors.
AB  - The identification of small molecule aminoimidazoles as potent and selective
      human beta-secretase inhibitors is reported. These analogues demonstrate low
      nannomolar potency for BACE1 in a FRET assay, exhibit comparable activity in a
      cell-based (ELISA) assay, and show >100x selectivity for the other structurally
      related aspartyl proteases BACE2, cathepsin D, renin, and pepsin. Our design
      strategy was supported by molecular modeling studies based on the cocrystal
      structure of the HTS-hit 3 in the BACE1 active site. These strategies enabled us
      to integrate pyridine and pyrimidine groups on 3 extending deep into the S3
      region of the BACE1 binding pocket and enhancing the ligand's potency. Compound
      (R)-37 displayed an IC50 value for BACE1 of 20 nM, cellular activity of 90 nM,
      and >100-fold selectivity over related aspartyl proteases. Acute oral
      administration of (R)-37 at 30 mg/kg resulted in a significant 71% reduction of
      plasma Abeta40 measured at the 6 h time point in a Tg2576 mouse model (p <
      0.001).

PMID- 19757825
TI  - Tetrastyryl-Bodipy dyes: convenient synthesis and characterization of elusive
      near IR fluorophores.
AB  - 1,3,5,7-Tetramethyl-Bodipy derivatives undergo Knoevenagel-type condensations
      with aromatic aldehydes to ultimately yield tetrastyryl-Bodipy derivatives. The
      resulting dyes absorb and emit strongly in the near IR. As the versatility of the
      Bodipy dyes are fully appreciated, these new tetrastyryl dyes are likely to be
      featured in a variety of functional supramolecular systems.

PMID- 19757826
TI  - Iron-catalyzed Negishi coupling toward an effective olefin synthesis.
AB  - A selective iron-catalyzed cross-coupling of alkyl halides with alkenylzinc
      reagents is described. Primary and secondary alkyl chlorides, bromides, and
      iodides take part in the reaction to give the corresponding olefins in good to
      excellent yields in a stereospecific manner. High functional group compatibility
      is also demonstrated by using combinations of substrates possessing rather
      reactive substituents.

PMID- 19757827
TI  - Design of 2D binary colloidal crystals in a nematic liquid crystal.
AB  - In this paper, we examine directed self-assembly in a 2D binary system of dipolar
      and quadrupolar colloidal particles with normal surface boundary conditions,
      dispersed in the nematic liquid crystal. Using the laser tweezers, we assembled a
      large variety of stable 2D colloidal crystal structures. In all analyzed
      structures, the particles, their surface treatment and the cell conditions were
      the same, which gives us the ability to systematically follow the evolution of
      colloidal assembly when many particles are present. We present an analogy between
      molecular self-assembly and organization of colloidal microspheres in liquid
      crystalline medium to extend the strategy for designing colloidal crystalline
      structures of different level of complexity.

PMID- 19757828
TI  - Unexpected regioselectivity in the synthesis of pyranonaphthoquinone via the
      Diels-Alder reaction.
AB  - The unusual regioselectivity in the Diels-Alder reactions of pyranoquinone 1 with
      (4,4-dimethoxybuta-1,3-dien-2-yloxy)trimethylsilane 2 are explored by both
      computations and experiments. The regioselectivity is controlled by the
      electrostatic interaction of the lactone ring-oxygen and the vicinal quinone
      oxygen on the transition structure, which can be tuned by the terminal methyl
      group of the butadienes.

PMID- 19757830
TI  - Examination of DFT and TDDFT methods I.
AB  - We investigated DFT and TDDFT methods in the sense of the molecular orbital (MO)
      theory and in the framework of the quantum theory of atoms in molecules (QT-AIM).
      The detailed investigations for the ground state and the pi --> pi* excited state
      of ethene clarified three aspects about DFT and TDDFT methods: First, the DFT
      methods included electron correlation effects by directly changing MO energies
      and MO electron density distributions. Second, MO occupation numbers explained
      why the delocalization indices (DIs) obtained from DFT wave function files
      apparently differed from DIs obtained from the conventional correlated wave
      function files. At last, the significant underestimation of the excitation energy
      for the pi --> pi* adiabatic excited states of ethene by TDDFT methods can be
      attributed to the exact degeneracy of HOMO (pi) and LUMO (pi*), a special case of
      charge transfer (CT) excited states.

PMID- 19757832
TI  - Examination of DFT and TDDFT methods II.
AB  - We investigated the isomerization energies for C(8) alkanes (n-octane and 2,2,3,3
      tetra-methyl butane) and 1-X-propenes (X = CH(3), F, Cl, Br) and the excited
      states for tropolone. The recently implemented TDDFT gradients enabled us to
      optimize the adiabatic excited-state structures and to obtain wave function files
      for excited-state electron density analyses with 25 functionals. The dispersion
      interactions had been found to be important for predicting the isomerization
      energies for n-octane and 2,2,3,3-tetra-methyl butane and for cis- and trans-1-X
      propenes (X = CH(3), F, Cl, Br). B3LYP failed to predict the isomerization
      energies for the first case but succeeded for the latter. We noticed that the
      integrated electron density and the merging contour values in the electron
      density difference plots were related to the isomerization energies; the DFT
      functionals (LSDA, BHandH, VSXC, and M052X) that could correctly account for the
      dispersion forces produced a greater electron density response for 2,2,3,3
      tetramethyl butane than n-octane. Although the faster proton transfer reaction
      rate in the A(1)B(2) excited state relative to the X(1)A(1) ground state of
      tropolone could be reproduced only by M052X, the three newly designed functionals
      (BMK, CAM-B3LYP, and M052X) apparently performed better than other DFT
      functionals. The C-C' bond lengths of the C(s) symmetry excited state were
      possibly underestimated by DFT methods; the underestimation of C-C' bond lengths
      contributed to the high proton transfer barriers in the A(1)B(2) excited state of
      tropolone.

PMID- 19757833
TI  - High-frequency behavior of the dynamic mobility and dielectric response of
      concentrated colloidal dispersions.
AB  - A matched asymptotic analysis of the system of equations governing the
      electrokinetic cell model of ref 4 (Ahualli, S.; Delgado, A.; Miklavcic, S.;
      White, L. R. Langmuir 2006, 22, 7041) is performed. Asymptotic expressions are
      obtained for the dynamic mobility and complex conductivity response of a dense
      suspension of charged spherical particles to an applied electric field. The
      asymptotic expressions are compared with full numerical calculations of the
      linear response functions as a function of surface (zeta) potential, electrolyte
      strength, and particle density. We find that the numerical procedure used is
      robust and highly accurate at a very high frequency under a wide range of double
      layer conditions. The asymptotic form for the dielectric response of the system
      is accurate to megahertz frequencies. The asymptotic formulas for the other
      response functions have limited viability as predictive tools within the current
      range of experimentally accessible frequencies but are useful as checks on
      numerical calculations.

PMID- 19757831
TI  - Investigating the biochemical impact of DNA damage with structure-based probes:
      abasic sites, photodimers, alkylation adducts, and oxidative lesions.
AB  - DNA sustains a wide variety of damage, such as the formation of abasic sites,
      pyrimidine dimers, alkylation adducts, or oxidative lesions, upon exposure to UV
      radiation, alkylating agents, or oxidative conditions. Since these forms of
      damage may be acutely toxic or mutagenic and potentially carcinogenic, it is of
      interest to gain insight into how their structures impact biochemical processing
      of DNA, such as synthesis, transcription, and repair. Lesion-specific molecular
      probes have been used to study polymerase-mediated translesion DNA synthesis of
      abasic sites and TT dimers, while other probes have been developed for
      specifically investigating the alkylation adduct O(6)-Bn-G and the oxidative
      lesion 8-oxo-G. In this review, recent examples of lesion-specific molecular
      probes are surveyed; their specificities of incorporation opposite target lesions
      compared to unmodified nucleotides are discussed, and limitations of their
      applications under physiologically relevant conditions are assessed.

PMID- 19757834
TI  - Application of free energy calculations at an ultrahigh temperature for
      estimation of molecular diffusivities and permeabilities in zeolite nanopores at
      an ambient temperature.
AB  - Molecular diffusivities and gas permeabilities through zeolite nanopores, which
      have been difficult to simulate directly from conventional molecular dynamics
      (MD), were estimated at an ambient temperature by performing the free energy
      calculation at an ultrahigh temperature. In this method, the hopping rate of a
      guest molecule is calculated based on transition state theory. Using these
      hopping rates, molecular self-diffusivities for a CH(4)/CF(4) binary mixture
      through an LTA-type zeolite, as well as those for each single component, are
      calculated at 300 K. The diffusivities of CF(4) are in the order of ca. 10(-14)
      m(2)/s at 300 K and thus are within an extremely slow molecular diffusion regime.
      Gas permeabilities of each single component at 300 K are also estimated by
      combining these calculated diffusivities with Fick's first law. For predicting
      CH(4) permeabilities, nonequilibrium MD is also applied for comparison, giving
      results within the same order, ca. 10(-12) molm/m(2)sPa. This methodology
      dramatically reduces computational time when predicting molecular diffusivity and
      gas permeability.

PMID- 19757835
TI  - Molecular dynamics simulations of the dynamic and energetic properties of alkali
      and halide ions using water-model-specific ion parameters.
AB  - The dynamic and energetic properties of the alkali and halide ions were
      calculated using molecular dynamics (MD) and free energy simulations with various
      different water and ion force fields including our recently developed water-model
      specific ion parameters. The properties calculated were activity coefficients,
      diffusion coefficients, residence times of atomic pairs, association constants,
      and solubility. Through calculation of these properties, we can assess the
      validity and range of applicability of the simple pair potential models and
      better understand their limitations. Due to extreme computational demands, the
      activity coefficients were only calculated for a subset of the models. The
      results qualitatively agree with experiment. Calculated diffusion coefficients
      and residence times between cation-anion, water-cation, and water-anion showed
      differences depending on the choice of water and ion force field used. The
      calculated solubilities of the alkali-halide salts were generally lower than the
      true solubility of the salts. However, for both the TIP4P(EW) and SPC/E water
      model-specific ion parameters, solubility was reasonably well-reproduced.
      Finally, the correlations among the various properties led to the following
      conclusions: (1) The reliability of the ion force fields is significantly
      affected by the specific choice of water model. (2) Ion-ion interactions are very
      important to accurately simulate the properties, especially solubility. (3) The
      SPC/E and TIP4P(EW) water-model-specific ion force fields are preferred for
      simulation in high salt environments compared to the other ion force fields.

PMID- 19757836
TI  - Dynamic disorder-driven substrate inhibition and bistability in a simple
      enzymatic reaction.
AB  - Conformations and catalytic rates of enzymes (biological catalysts) fluctuate
      over a wide range of time scales. Recent experimental and theoretical
      investigations demonstrated case studies where the enzymatic catalysis rate
      follows the Michaelis-Menten (MM) rate law despite molecular fluctuations. In
      this paper, we investigate deviations from MM law and their effects on the
      dynamical behavior of the enzymatic network. We consider a simple kinetic scheme
      for a single substrate enzymatic reaction in which the product release step is
      treated explicitly. We examine how conformational fluctuations affect the
      underlying rate law in the quasi-static limit when conformational dynamics is
      very slow in one of the states. Our numerical results and analytically solvable
      model indicate that slow conformational fluctuations of the enzyme-substrate
      complex lead to non-MM behavior, substrate inhibition, and possible bistability
      of the reaction network.

PMID- 19757837
TI  - Interactions of the osmolyte glycine betaine with molecular surfaces in water:
      thermodynamics, structural interpretation, and prediction of m-values.
AB  - Noncovalent self-assembly of biopolymers is driven by molecular interactions
      between functional groups on complementary biopolymer surfaces, replacing
      interactions with water. Since individually these interactions are comparable in
      strength to interactions with water, they have been difficult to quantify.
      Solutes (osmolytes, denaturants) exert often large effects on these self-assembly
      interactions, determined in sign and magnitude by how well the solute competes
      with water to interact with the relevant biopolymer surfaces. Here, an osmometric
      method and a water-accessible surface area (ASA) analysis are developed to
      quantify and interpret the interactions of the remarkable osmolyte glycine
      betaine (GB) with molecular surfaces in water. We find that GB, lacking hydrogen
      bond donors, is unable to compete with water to interact with anionic and amide
      oxygens; this explains its effectiveness as an osmolyte in the Escherichia coli
      cytoplasm. GB competes effectively with water to interact with amide and cationic
      nitrogens (hydrogen bonding) and especially with aromatic hydrocarbon (cation
      pi). The large stabilizing effect of GB on lac repressor-lac operator binding is
      predicted quantitatively from ASA information and shown to result largely from
      dehydration of anionic DNA phosphate oxygens in the protein-DNA interface. The
      incorporation of these results into theoretical and computational analyses will
      likely improve the ability to accurately model intra- and interprotein
      interactions. Additionally, these results pave the way for development of solutes
      as kinetic/mechanistic and thermodynamic probes of conformational changes and
      formation/disruption of molecular interfaces that occur in the steps of
      biomolecular self-assembly processes.

PMID- 19757838
TI  - Barrier to linearity and anharmonic force field of the ketenyl radical.
AB  - The troublesome barrier to linearity of the ketenyl radical (HCCO) is precisely
      determined using state-of-the-art computations within the focal point approach,
      by combining complete basis set extrapolation, utilizing the aug-cc-pVXZ (X = D,
      T, Q, 5, 6) family of basis sets, with electron correlation treatments as
      extensive as coupled cluster theory with single, double, triple, and perturbative
      quadruple excitations [CCSDT(Q)]. Auxiliary terms such as diagonal Born
      Oppenheimer corrections (DBOCs) and relativistic contributions are included. To
      gain a definitive theoretical treatment and to assess the effect of higher-order
      correlation on the structure of HCCO, we employ a composite approximation (c
      approximately ) to all-electron (AE) CCSDT(Q) theory at the complete basis set
      (CBS) limit for geometry optimizations. A final classical barrier to linearity of
      630 +/- 30 cm(-1) is obtained for reaching the (2)Pi Renner-Teller configuration
      of HCCO from the (2)A'' ground state. Additionally, we compute fundamental
      vibrational frequencies and other spectroscopic constants by application of
      second-order vibrational perturbation theory (VPT2) to the full quartic force
      field at the AE-CCSD(T)/aug-cc-pCVQZ level. The resulting (nu(1), nu(2), nu(5))
      fundamental frequencies of (3212, 2025, 483) cm(-1) agree satisfactorily with the
      experimental values (3232, 2023, 494) cm(-1).

PMID- 19757839
TI  - The replacement of His(4) in angiotensin IV by conformationally constrained
      residues provides highly potent and selective analogues.
AB  - The histidine residue in angiotensin IV was replaced by various conformationally
      constrained amino acids. The substitution of the His(4)-Pro(5) dipeptide sequence
      by the constrained Trp analogue Aia-Gly, in combination with beta(2)hVal
      substitution at the N-terminus, provided a new stable analogue H-(R)-beta(2)hVal
      Tyr-Ile-Aia-Gly-Phe-OH (AL-40) that is a potent ligand for the Ang IV receptor
      IRAP and selective versus AP-N and the AT1 receptor.

PMID- 19757840
TI  - Synthesis and antiprotozoal properties of pentamidine congeners bearing the
      benzofuran motif.
AB  - Forty-eight cationically substituted pentamidine congeners possessing benzofuran
      rings were synthesized by a copper mediated heteroannulation of substituted o
      iodophenols with phenyl acetylenes. Activities of compounds 1-48 against
      Trypanosoma brucei rhodesiense, Plasmodium falciparum, and Leishmania donovani
      and cytotoxicities for mammalian cells were influenced by the nature of cationic
      substituents, placement of the benzofuran fragment, and the length of the carbon
      linker between aromatic moieties. Several dications exhibited superior
      antiplasmodial and antileishmanial potencies compared to pentamidine.

PMID- 19757842
TI  - Potential energy curves for the (1)Sigma(+) and (1,3)Pi states of CO.
AB  - Ab initio potential energy curves of CO are calculated to address a number of
      problems remaining in the interpretation of the experimental VUV absorption
      spectra. The calculations are of the type SCF MRSD-CI. We employed the aug-cc
      pVQZ basis set for both carbon and oxygen, augmented with twelve diffuse
      functions, of s-, p-, and d-type, located on both atomic centers. We focus on the
      energy region 85,000 cm(-1) < E < 110,000 cm(-1) characterized by strong
      interactions between Rydberg and valence states. In this work we deal
      specifically with the (1)Sigma(+), (1)Pi, and (3)Pi states lying in this region.
      Some of the relevant findings are as follows: The minimum of the C'(1)Sigma(+)
      valence state is found 1920 cm(-1) above the value inferred from an extrapolation
      of experimental data. A new (1)Pi valence state, labeled E', is found to perturb
      strongly the (X(2)Sigma(+))3ppi E(1)Pi Rydberg state. The electrostatic
      perturbation of the (X(2)Sigma(+))3ppi c(3)Pi Rydberg state by the k(3)Pi valence
      state is confirmed. The energy position of the (A(2)Pi)3ssigma (3)Pi state, the
      triplet companion of the W(1)Pi Rydberg state, is predicted.

PMID- 19757843
TI  - Mixing behavior and interphase formation in the diethylene triamine-water system
      studied by optical imaging and spatially resolved Brillouin scattering.
AB  - The injection of water beneath liquid diethylene triamine in a glass cuvette
      leads to an unexpected phase evolution behavior of the two liquids. The space and
      time dependent developments of the molecular structure and the underlying
      transport associated with mixing of the two liquids are monitored by optical
      imaging and scanning Brillouin microscopy. Apparently, results obtained by either
      experimental technique lead to disparate interpretations. Whereas optical imaging
      suggests the existence of a two phase structure, which disappears within a few
      hours, acoustic microscopy indicates the evolution of a more gradually evolving
      and longer-lived three phase structure. According to molecular acoustics, the
      transport of diethylene triamine into water and vice versa behaves strongly
      asymmetric in time. An attempt is made to reconcile the observed optical and
      acoustic manifestations of the mixing process on the basis of molecular complex
      formation.

PMID- 19757844
TI  - Polar mixtures under nanoconfinement.
AB  - We present results from molecular dynamics simulations describing structural and
      dynamical characteristics of equimolar mixtures of water and acetonitrile,
      confined between two silica walls separated at interplate distances of d=0.6, 1,
      and 1.5 nm. Two different environments were investigated: a first one where wall
      solvent dispersion forces prevail (hydrophobic confinement) and a second one in
      which the terminal O atoms at the silica surface are transformed into silanol
      groups (hydrophilic confinement). For the former case, we found that, at the
      shortest interplate distance examined, the confined region is devoid of water
      molecules. At an interplate distance of the order of 1 nm, water moves into the
      confined region, although, in all cases, there is a clear enhancement of the
      local concentration of acetonitrile in detriment of that of water. Within
      hydrophilic environments, we found clear distinctions between a layer of bound
      water lying in close contact with the silica substrates and a minority of
      confined water that occupies the inner liquid slab. The bound aqueous layer is
      fully coordinated to the silanol groups and exhibits minimal hydrogen bonding
      with the second solvation layer, which exclusively includes acetonitrile
      molecules. Dynamical characteristics of the solvent mixture are analyzed in terms
      of diffusive and rotational motions in both environments. Compared to bulk
      mixtures, we found significant retardations in all dynamical modes, with those
      ascribed to water molecules bound to the hydrophilic plates being the most
      dramatic.

PMID- 19757845
TI  - The influence of internal charge transfer on nonradiative decay in substituted
      terthiophenes.
AB  - Photophysical data for a series of end substitued 3',4'-dibutyl-2,2':5',2''
      terthiophenes are reported. Static absorption and fluorescence, quantum yields,
      time-resolved fluorescence, and time- and frequency-resolved pump-probe spectra
      are applied to investigate excited state relaxation in bromo, nitro, and
      tricyanovinyl substituted species in a variety of solvents. The effect of solvent
      polarizability and end-group substitution is discussed in the context of charge
      transfer in the excited state and its impact on nonradiative decay rates. In
      solution at room temperature, both symmetric and asymmetric addition of electron
      withdrawing end groups generate an excited state with substantial charge transfer
      character. Solvent polarizability has a significant influence on the excited
      state dynamics in the charge transfer compounds. Examples include a 20-fold
      reduction in the intersystem crossing rate going from hexane to toluene and an
      order of magnitude increase in the internal conversion rate between toluene and
      acetone. The results demonstrate that the impact of the substituents on
      intramolecular charge transfer, and the resulting amplification of the
      interactions between the excited state(s) and the local molecular environment,
      can dramatically change the excited state relaxation dynamics in substituted
      terthiophenes.

PMID- 19757846
TI  - Revisiting the laser dye Styryl-13 as a reference near-infrared fluorophore:
      implications for the photoluminescence quantum yields of semiconducting single
      walled carbon nanotubes.
AB  - The near-infrared (NIR) polymethine dye Styryl-13 emitting at approximately 925
      nm has recently been suggested as a reference fluorophore for determining the
      quantum yield (QY) of the NIR photoluminescence of dispersed single-walled carbon
      nanotubes (SWNTs). Ju et al. reported the QY for SWNTs to be as high as 20% on
      the basis of 11% QY for Styryl-13 in methanol (Science 2009, 323, 1319). We
      directly compared the fluorescence of Styryl-13 and Styryl-20 (emitting at
      approximately 945 nm) with that of the standard fluorophore Rhodamine 6G using a
      spectrometer with a broad visible-NIR detection range. QYs of 2.0 (4.5) and 0.52
      (0.80)% were determined for Styryl-13 and Styryl-20 in methanol (propylene
      carbonate), respectively. Correspondingly, the above-mentioned photoluminescence
      efficiency of SWNTs appears to be strongly overestimated. We also discuss singlet
      oxygen as an alternative NIR reference. A total QY of 1.4% was measured for the
      emission of singlet oxygen at 1275 nm, as photosensitized by C70 fullerene in air
      saturated carbon tetrachloride.

PMID- 19757847
TI  - Decomposition of methylbenzyl radicals in the pyrolysis and oxidation of xylenes.
AB  - Alkyl benzyl radicals are important initial products in thermal and combustion
      reactions of substituted aromatic fuels. The decomposition reactions of the three
      isomeric methylbenzyl radicals, formed as primary products in xylene combustion,
      are studied theoretically and are shown to be significantly more complex than
      previously reported. Thermochemical properties are calculated using the G3X and
      G3SX model chemistries, with isodesmic and atomization work reactions. G3X
      atomization calculations reproduce heats of formation for the 14 reference
      species in the work reactions to a mean unsigned error of 0.23 kcal mol(-1), and
      maximum error of 0.70 kcal mol(-1), slightly outperforming the G3SX method. For
      the target molecules the isodesmic and atomization heats of formation agree to
      within 0.20 kcal mol(-1), on average. We posit that this study approaches the
      crossover point at which atomization calculations offer improved accuracy over
      isodesmic ones, for these closed-shell hydrocarbons. Our results suggest that m
      xylylene is not the decomposition product of m-methylbenzyl, as was previously
      reported. Instead, the m-methylbenzyl radical decomposes to p-xylylene (and
      perhaps some of the less stable o-xylylene) via a ring-contraction/methylene
      migration (RCMM) mechanism, with activation energy of around 70 kcal mol(-1). At
      higher temperatures m-methylbenzyl is predicted to also decompose to 2- and 3
      methylfulvenallene + H, with activation energy of around 84 kcal mol(-1). The o
      methylbenzyl radical is shown to primarily decompose to o-xylylene + H with bond
      dissociation energy of 67.3 kcal mol(-1), with fulvenallene + CH3 proposed as a
      minor product set. Finally, the p-methylbenzyl radical decomposes solely to p
      xylylene + H with bond dissociation energy 61.5 kcal mol(-1). Rate expressions
      are estimated for all reported reactions, based on thermochemical kinetic
      considerations, with further modeling along with detailed experiments needed to
      better refine rate constants and branching ratios for methylbenzyl radical
      decomposition. These calculated reaction mechanisms and rate constants for
      methylbenzyl radical decomposition are consistent with the experimental data. Our
      results help explain the ignition behavior of the xylenes, and should lead to
      improved kinetic models for combustion of these and other alkylated aromatic
      hydrocarbons.

PMID- 19757848
TI  - On the origin of small band gaps in alternating thiophene-thienopyrazine
      oligomers.
AB  - We have studied experimentally and theoretically the optical and electrochemical
      properties of small band gap oligo(7,7'-bis(thiophen-2-yl)-5,5'-bisthieno[3,4
      b]pyrazine)s with alternating blocks of bithiophene units and bisthienopyrazine
      units up to a total length of 16 units. The optical absorptions of the ground
      state, the triplet excited state, and the corresponding radical cation have been
      identified and shift to lower energy with increasing chain length. The optical
      absorption correlates well with quantum chemical calculations and the
      electrochemical band gap. We show that reduction of the band gap with chain
      length results from a significant rise of the HOMO level and a moderate reduction
      of the LUMO energy. Comparison of the chain length dependence of the transition
      energy at maximum absorption (Emax) and of the redox potentials with previously
      published data on oligothiophenes and related mixed thiophene-thienopyrazine
      oligomers shows that the reduction of Emax is more easily induced by increasing
      the number of thienopyrazine units than by extending the chain, mainly because
      thienopyrazine is both a better donor and a better acceptor than thiophene.
      Strong interactions between neighboring thienopyrazine units, with some possible
      admixing of quinoid character, are the main cause of the small band gap in these
      oligomers.

PMID- 19757849
TI  - Counterintuitive substituent effect of the ethynyl group in ion-pi interactions.
AB  - In this article, we report a high-level theoretical study (SCS-RI-MP2(full)/aug
      cc-pVTZ) that deals with the substituent effect of the ethynyl group on ion-pi
      interactions in 1,3,5-triethynylbenzene systems. The ethynyl group is able to act
      as an electron-withdrawing group, thus favoring the anion-pi interaction.
      Unexpectedly, it has little influence on the cation-pi interaction. This behavior
      has been studied by examining the geometrical and energetic features of the
      complexes, AIM, and charge analyses and partitioning the interaction energy. The
      simultaneous interaction of 1,3,5-triethynylbenzene with cations and anions by
      opposite sides of the ring has also been studied.

PMID- 19757850
TI  - Theoretical study of the primary processes in the thermal decomposition of
      hydrazinium nitroformate.
AB  - The primary reactions of the thermal decomposition of hydrazinium nitroformate
      (HNF) as well as ammonium nitroformate (ANF) were investigated theoretically
      using the G3 multilevel procedure. Calculations were performed for the reactions
      in the gas phase and in the melt using a simplified model of the latter. The
      influence of the melt on the reaction barriers was taken into account by
      calculation of the solvation free energies using a PCM model. In contrast with
      many other energetic salts, the ionic salt structures of the HNF and ANF were
      found to be minima on the PES. However, the most energetically favorable
      structures of the HNF and ANF in the gas phase are H-bonded complexes. In the
      melt, on the contrary, the ionic structure is lowest in free energy because of
      solvation effects. In both the gas phase and melt, the HNF decomposes preferably
      to nitroform and hydrazine. This fact agrees well with the experimentally
      observed absence of HNF among the gas-phase decomposition products. Thermolysis
      of HNF occurs mainly through the intermediacy of nitroform; computations do not
      support the suggestion that the aci-nitroform is an important intermediate of HNF
      thermolysis. The primary dissociation reactions of ANF resemble those of the HNF.

PMID- 19757851
TI  - DFT study on the mechanisms of stereoselective C2-vinylation of 1-substituted
      imidazoles with 3-phenyl-2-propynenitrile.
AB  - Recently, the first examples of direct vinylation of 1-substituted imidazoles at
      the 2-position of the imidazole nucleus have been described (J. Org. Chem. 2008,
      73, 9155-9157). 1-Substituted imidazoles are C(2)-vinylated with 3-phenyl-2
      propynenitrile at room temperature without catalyst and solvent to afford 3-(1
      organyl-1H-imidazol-2-yl)-3-phenyl-2-propenenitriles, mainly (ca. 95%) as (Z)
      isomers, in 56-88% yield. Nevertheless, the stereoselectivity of vinylation,
      which has been elusive over the past decades, is still a big problem to explain.
      In this paper, the reaction mechanisms of stereoselective C(2)-vinylation of 1
      methylimidazole with 3-phenyl-2-propynenitrile have been investigated using
      density functional theory (DFT). The geometries of the reactants, transition
      states, intermediates, and products were optimized at the B3LYP/6-31G(d,p) level.
      The calculated results reveal that the reaction contains three processes:
      formation of zwitterion, proton transfer, and ring rearrangement. Four possible
      reaction channels are shown, including two (E)-isomer channels and two (Z)-isomer
      channels. One of the (Z)-isomer channels has the lowest energy barrier among all
      the four channels, with the highest energy barrier for 83.62 kJ/mol, so it occurs
      more often than the others at room temperature, which is in good agreement with
      experiment. Further calculations of solvation effects show that the title
      reaction can be carried out more smoothly in the gas phase.

PMID- 19757852
TI  - Solvation effects on isomeric preferences of curium(iii) complexes with
      multidentate phosphonopropionic acid ligands: CmH(2)PPA(2+) and CmHPPA(+)
      complexes.
AB  - We have carried out both time-resolved laser fluorescence spectroscopic and
      computational studies on the complexes of curium(III) with multidentate
      Phosphonopropionic (PPA) acid ligands. A number of complexes of Cm(III) with
      these ligands, such as CmH(2)PPA(2+), CmHPPA(+), Cm[H(2)PPA](2)(+), and
      Cm[HPPA](2)(-) have been studied. Our computational studies focused on all
      possible isomers in the gas phase and aqueous solution so that the relative
      binding strengths of carboxylic versus phosphoric groups can be assessed in these
      multidentate systems. The solvation effects play an important role in the
      determination of the preferred configurations and binding propensities of
      carboxylate versus phosphate sites of the ligands. Our computations assess the
      relative strengths of single and multidentate complexes in solutions for these
      systems. The computed free energies of solvation explain the experimentally
      observed fluorescence spectra and the lifetimes of these complexes in that as
      more water molecules are displaced from the first hydration sphere by the ligands
      that bind to Cm(III), the fluorescence lifetime increases. We have found that the
      most stable complex for CmH(2)PPA(2+) in the aqueous phase exhibits a monodentate
      complex where the curium(III) is bound to the deprotonated phosphate oxygen atom.
      Our computations support the observed longer fluorescence lifetime of
      CmH(2)PPA(2+) (112 mus) compared to the free Cm(III) aquo ion (65 mus),
      suggesting a greater degree of H(2)O displacement from the hydration sphere. For
      the Cm-HPPA(+) complex, we find a tridentate form as the most stable structure
      which supports the observed fluorescence lifetime for the CmHPPA(+) complex (172
      mus), confirming the removal of up to six water molecules from the inner
      hydration sphere. The relative stabilities of the complexes are found to vary
      substantially between the gas phase and solution, indicating a major role of
      solvation in the relative stabilities of these complexes.

PMID- 19757853
TI  - Identification of antiadipogenic constituents of the rhizomes of Anemarrhena
      asphodeloides.
AB  - Three new phenolic compounds, (E)-4'-demethyl-6-methyleucomin (1), anemarcoumarin
      A (2), and anemarchalconyn (3), were isolated from an ethyl acetate extract of
      the rhizomes of Anemarrhena asphodeloides, together with seven known compounds (4
      10). The structures of the new compounds (1-3) were determined on the basis of
      spectroscopic data interpretation. Compound 3 exhibited a potent inhibitory
      effect against the differentiation of preadipocyte 3T3-L1 cells with an IC50
      value of 5.3 microM.

PMID- 19757854
TI  - Platinum(II) terpyridyl acetylide complexes on platinized TiO(2): toward the
      photogeneration of H(2) in aqueous media.
AB  - New platinum(II) terpyridyl acetylide complexes having the ability to bind to
      TiO(2) have been synthesized and assayed in their ability to sensitize platinized
      titanium dioxide for the photogeneration of H(2) using visible light (lambda >
      410 nm). Specifically, the complexes [Pt(tpy-phen-COOH)(C[triple bond]C
      C(6)H(5))]Cl (1), where tpy-phen-COOH = 4'-(4-carboxyphenyl)
      [2,2';6',2'']terpyridine and C[triple bond]C-C(6)H(5) = phenylacetylide, and
      [Pt(tpy-COOH)(C[triple bond]C-C(6)H(5))]Cl (2), where tpy-COOH = 4'-carboxy
      2,2';6',2''-terpyridine, were prepared to investigate the effectiveness of
      attachment and proximity to the TiO(2) surface on hydrogen yield. Both complexes
      1 and 2 sensitize the photogeneration of hydrogen, but produce fewer turnovers
      than the unbound chromophore, [Pt(ttpy)(C[triple bond]C-C(6)H(5))]PF(6) (5). On
      the basis of these observations and electrochemical data, a major limitation to
      the effectiveness of these chromophores is their instability upon oxidation. To
      attempt to remedy this problem, two donor-chromophore (D-C) dyads, [Pt(tpy-phen
      COOH)(C[triple bond]C-C(6)H(4)CH(2)-PTZ)]PF(6) (3), where C[triple bond]C
      C(6)H(4)CH(2)-PTZ = N-(4-ethynylbenzyl)-phenothiazine and [Pt(tpy-COOH)(C[triple
      bond]C-C(6)H(4)CH(2)-PTZ)]Cl (4) were prepared to function as TiO(2)-attached
      sensitizers. Transient absorption measurements have shown that the PTZ moiety
      reductively quenches the Pt center in several picoseconds. While the resultant
      PTZ(+) radical cation is capable of oxidizing rapidly the triethanolamine
      sacrificial electron donor, dyads 3 and 4 attached to platinized TiO(2) do not
      function to generate hydrogen upon irradiation, in contrast with results seen for
      1 and 2.

PMID- 19757855
TI  - Chrotacumines A-D, chromone alkaloids from Dysoxylum acutangulum.
AB  - Four new chromone alkaloids, chrotacumines A-D (1-4), consisting of a 5,7
      dihydroxy-2-methylchromone, an N-Me piperidine ring, and an ester side chain were
      isolated from Dysoxylum acutangulum, and their structures including absolute
      configurations were elucidated on the basis of spectroscopic data interpretation
      including 2D NMR, CD spectra, and X-ray analysis. The known compound rohitukine
      (5) showed moderate cytotoxicity against human HL-60 promyelocytic leukemia and
      HCT-116 colon cancer cells.

PMID- 19757856
TI  - Axiphenylalaninium and axityrosinium, modified amino acids from the Mediterranean
      marine sponge Axinella polypoides.
AB  - Two new modified amino acids, axiphenylalaninium (1) and axityrosinium (2), along
      with four known metabolites, C2-alpha-D-mannosylpyranosyl-L-tryptophan (3), N3,5'
      cycloxanthosine (4), palythine (5), and taurine, were isolated from the marine
      sponge Axinella polypoides collected in the Mediterranean Sea. The structures
      were determined by spectroscopic studies and confirmed by X-ray analysis and
      chemical modifications.

PMID- 19757857
TI  - Antioxidant effects of xanthohumol and functional impact on hepatic ischemia
      reperfusion injury.
AB  - Therapeutic effects of dietary flavonoids have been attributed mainly to their
      antioxidant capacity. Xanthohumol (1), a prominent flavonoid of the hop plant,
      Humulus lupulus, was investigated for its antioxidant potential and for its
      effect on NF-kappaB activation. To examine the biological relevance of 1, a
      hepatic ischemia/reperfusion model was chosen as a widely accepted model of
      oxidative stress generation. The impact of 1 on endogenous antioxidant systems,
      on the NF-kappaB signal transduction pathway as well as on apoptotic parameters,
      and on hepatic tissue damage was evaluated. Compound 1 markedly decreased the
      level of reactive oxygen species in vitro. Furthermore, levels of enzymatic and
      nonenzymatic antioxidants were restored after pretreatment in postischemic
      hepatic tissue, and lipid peroxidation was attenuated. NF-kappaB activity was
      reduced in vitro as well as in hepatic tissue after ischemia/reperfusion upon
      pretreatment with 1. In addition, the phosphorylation of Akt was markedly
      inhibited. Surprisingly, 1 decreased the expression of the antiapoptotic protein
      Bcl-X and increased caspase-3 like-activity, a proapoptotic parameter. Moreover,
      hepatic tissue damage as well as TNF-alpha levels increased in xanthohumol
      pretreated liver tissue after ischemia/reperfusion. In summary, xanthohumol did
      not protect against ischemia/reperfusion injury in rat liver, despite its
      antioxidant and NF-kappaB inhibitory properties.

PMID- 19757858
TI  - Phosphorus doped Zn(1-x)Mg(x)O nanowire arrays.
AB  - We demonstrate the growth of phosphorus doped Zn(1-x)Mg(x)O nanowire (NW) using
      pulsed laser deposition. For the first time, p-type Zn(0.92)Mg(0.08)O:P NWs are
      likely obtained in reference to atomic force microscopy based piezoelectric
      output measurements, X-ray photoelectron spectroscopy, and the transport property
      between the NWs and a n-type ZnO film. A shallow acceptor level of approximately
      140 meV is identified by temperature-dependent photoluminescence. A piezoelectric
      output of 60 mV on average has been received using the doped NWs. Besides a
      control on NW aspect ratio and density, band gap engineering has also been
      achieved by alloying with Mg to a content of x = 0.23. The alloyed NWs with
      controllable conductivity type have potential application in high-efficiency all
      ZnO NWs based LED, high-output ZnO nanogenerator, and other optical or electrical
      devices.

PMID- 19757859
TI  - The effect of physical exercise on endothelial function.
AB  - Endothelium is essential for maintenance of health of the vessel wall and for the
      local regulation of vascular tone and structure and haemostasis. Regular physical
      exercise, which is known to promote a favourable cardiovascular state, may
      improve endothelial function via several mechanisms. Indeed, it augments blood
      flow and laminar shear stress, resulting in increased nitric oxide production and
      bioavailability. In this regard, the beneficial effects of training on
      endothelial function can be mediated in a number of ways, including synthesis of
      molecular mediators, changes in neurohormonal release and oxidant/antioxidant
      balance. On the other hand, physical exercise can also elicit systemic molecular
      pathways connected with angiogenesis and chronic anti-inflammatory action with
      consequent modification of the endothelial function. However, its benefit depends
      on the type and intensity of training performed. While strenuous exercise
      increases oxidative metabolism and produces a pro-oxidant environment, only
      regular moderate physical activity promotes an antioxidant state and preserves
      endothelial function. Thus, exercise may have a beneficial effect on the
      development of cardiovascular disease through preserving endothelial function.

PMID- 19757861
TI  - The analysis and utilization of cycling training data.
AB  - Most mathematical models of athletic training require the quantification of
      training intensity and quantity or 'dose'. We aim to summarize both the methods
      available for such quantification, particularly in relation to cycle sport, and
      the mathematical techniques that may be used to model the relationship between
      training and performance. Endurance athletes have used training volume
      (kilometres per week and/or hours per week) as an index of training dose with
      some success. However, such methods usually fail to accommodate the potentially
      important influence of training intensity. The scientific literature has provided
      some support for alternative methods such as the session rating of perceived
      exertion, which provides a subjective quantification of the intensity of
      exercise; and the heart rate-derived training impulse (TRIMP) method, which
      quantifies the training stimulus as a composite of external loading and
      physiological response, multiplying the training load (stress) by the training
      intensity (strain). Other methods described in the scientific literature include
      'ordinal categorization' and a heart rate-based excess post-exercise oxygen
      consumption method. In cycle sport, mobile cycle ergometers (e.g. SRM and
      PowerTap) are now widely available. These devices allow the continuous
      measurement of the cyclists' work rate (power output) when riding their own
      bicycles during training and competition. However, the inherent variability in
      power output when cycling poses several challenges in attempting to evaluate the
      exact nature of a session. Such variability means that average power output is
      incommensurate with the cyclist's physiological strain. A useful alternative may
      be the use of an exponentially weighted averaging process to represent the data
      as a 'normalized power'. Several research groups have applied systems theory to
      analyse the responses to physical training. Impulse-response models aim to relate
      training loads to performance, taking into account the dynamic and temporal
      characteristics of training and, therefore, the effects of load sequences over
      time. Despite the successes of this approach it has some significant limitations,
      e.g. an excessive number of performance tests to determine model parameters. Non
      linear artificial neural networks may provide a more accurate description of the
      complex non-linear biological adaptation process. However, such models may also
      be constrained by the large number of datasets required to 'train' the model. A
      number of alternative mathematical approaches such as the Performance-Potential
      Metamodel (PerPot), mixed linear modelling, cluster analysis and chaos theory
      display conceptual richness. However, much further research is required before
      such approaches can be considered as viable alternatives to traditional impulse
      response models. Some of these methods may not provide useful information about
      the relationship between training and performance. However, they may help
      describe the complex physiological training response phenomenon.

PMID- 19757860
TI  - Caffeine and anaerobic performance: ergogenic value and mechanisms of action.
AB  - The effect caffeine elicits on endurance performance is well founded. However,
      comparatively less research has been conducted on the ergogenic potential of
      anaerobic performance. Some studies showing no effect of caffeine on performance
      used untrained subjects and designs often not conducive to observing an ergogenic
      effect. Recent studies incorporating trained subjects and paradigms specific to
      intermittent sports activity support the notion that caffeine is ergogenic to an
      extent with anaerobic exercise. Caffeine seems highly ergogenic for speed
      endurance exercise ranging in duration from 60 to 180 seconds. However, other
      traditional models examining power output (i.e. 30-second Wingate test) have
      shown minimal effect of caffeine on performance. Conversely, studies employing
      sport-specific methodologies (i.e. hockey, rugby, soccer) with shorter duration
      (i.e. 4-6 seconds) show caffeine to be ergogenic during high-intensity
      intermittent exercise. Recent studies show caffeine affects isometric maximal
      force and offers introductory evidence for enhanced muscle endurance for lower
      body musculature. However, isokinetic peak torque, one-repetition maximum and
      muscular endurance for upper body musculature are less clear. Since relatively
      few studies exist with resistance training, a definite conclusion cannot be
      reached on the extent caffeine affects performance. It was previously thought
      that caffeine mechanisms were associated with adrenaline (epinephrine)-induced
      enhanced free-fatty acid oxidation and consequent glycogen sparing, which is the
      leading hypothesis for the ergogenic effect. It would seem unlikely that the
      proposed theory would result in improved anaerobic performance, since exercise is
      dominated by oxygen-independent metabolic pathways. Other mechanisms for caffeine
      have been suggested, such as enhanced calcium mobilization and phosphodiesterase
      inhibition. However, a normal physiological dose of caffeine in vivo does not
      indicate this mechanism plays a large role. Additionally, enhanced Na+/K+ pump
      activity has been proposed to potentially enhance excitation contraction coupling
      with caffeine. A more favourable hypothesis seems to be that caffeine stimulates
      the CNS. Caffeine acts antagonistically on adenosine receptors, thereby
      inhibiting the negative effects adenosine induces on neurotransmission, arousal
      and pain perception. The hypoalgesic effects of caffeine have resulted in
      dampened pain perception and blunted perceived exertion during exercise. This
      could potentially have favourable effects on negating decreased firing rates of
      motor units and possibly produce a more sustainable and forceful muscle
      contraction. The exact mechanisms behind caffeine's action remain to be
      elucidated.

PMID- 19757862
TI  - Psychological hallmarks of skilled golfers.
AB  - In this article, the psychological hallmarks of skilled golfers (professionals
      and amateurs with handicaps of </=4) are investigated. Professional golfers
      believe that attitude, desire and motivation are important psychological
      qualities necessary to succeed in tournaments. They are committed to golf, have
      goals they strive for, make plans, evaluate their performance and systematically
      train towards improving their game. The study of skilled golfers' traits, as
      measured by 16 personality factors, has provided ambiguous results and there may
      be more complex associations not yet investigated in golf. The effect of mood and
      emotions on golf scores seems to be individual. Differences in personality may
      explain why mood states, measured by mood state profiles, have not shown a strong
      correlation to golf scores. Task focus, confidence, imagery, patience, ability to
      focus on one shot at a time and performing automatically have been found to be
      important during competition. These variables need to be further researched
      before, during and after the swing. The psychological processes needed before,
      during and after the swing differ and should be further specified. A decrease in
      heart rate and a lower cortical activity moment before the swing may be signs of
      an optimal performance state. The effect of coping strategies may vary over time,
      and players should be able to switch and combine different strategies. Pre-shot
      routine is associated with performance. However, it is not clear if consistency
      of total duration and behavioural content in pre-shot routine cause improved
      performance. Pre-shot routine may also be an effect of psychological processes,
      such as a different task focus. It may facilitate an automatic execution of
      technique, which can lead to better performance. The psychological variables
      needed for competitive golf should be related to the physical, technical and game
      statistical variables in coaching and future research.

PMID- 19757863
TI  - Let them roam free? Physiological and psychological evidence for the potential of
      self-selected exercise intensity in public health.
AB  - In recommending physical activity for public health, authors have advocated
      either an approach in which the participant is to follow a prescription developed
      by a professional or an approach based on the participants' own preferences. This
      review explores the potential for convergence between these two approaches by
      examining: (i) whether the exercise intensity that participants select is within
      the range recommended by the American College of Sports Medicine for the
      development and maintenance of cardiorespiratory fitness and health; (ii) what is
      known about the determinants of self-selected intensity and the factors
      underlying interindividual differences; and (iii) the psychological consequences
      of imposing a level of intensity compared with allowing participants to select
      their preferred level. The results indicate that, among middle-aged or older,
      sedentary or obese participants, or those in cardiac rehabilitation, self
      selected exercise intensities are, on average, within the recommended range.
      However, some individuals select levels well below the recommended range and
      others select near-maximal levels. Most individuals apparently select intensities
      proximal to their ventilatory or lactate threshold, presumably because higher
      intensities would reduce pleasure. The factors underlying the large
      interindividual differences in self-selected intensity remain poorly understood.
      Imposed intensities lead to declines in pleasure, even when they exceed the self
      selected level by a small amount. These results demonstrate the compatibility of
      prescription-based and preference-based approaches. Public health practitioners
      can consider self-selected intensity as an appropriate option.

PMID- 19757864
TI  - The role of patient preferences in cost-effectiveness analysis: a conflict of
      values?
AB  - This paper reviews the role of patient preferences within the framework of cost
      effectiveness analysis (CEA). CEA typically adopts a system-wide perspective by
      focusing upon efficiency across groups in the allocation of scarce healthcare
      resources, whereas treatment decisions are made over individuals. However,
      patient preferences have been shown to have a direct impact on the outcome of an
      intervention via psychological factors or indirectly via patient
      adherence/compliance rates. Patient values may also be in conflict with the
      results of CEA through the valuation of benefits. CEA relies heavily on the QALY
      model to reflect individual preferences, although the healthy year equivalent
      offers an alternative measure that may be better at taking individual preferences
      into account. However, both measures typically use mean general population or
      mean patient values and therefore create conflict with individual-level
      preferences. For CEA to reflect practice, it must take into account the impact of
      individual patient preferences even where general population preferences are used
      to value the benefits of interventions. Patient preferences have implications for
      cost effectiveness through costs and outcomes, and it is important that cost
      effectiveness models incorporate these through its structure (e.g. allowing for
      differing compliance rates) and parameter values, including clinical
      effectiveness. It will also be necessary to try to predict patient preferences in
      order to estimate any impact on cost effectiveness through analyses of revealed
      and stated preference data. It is recognized that policy makers are concerned
      with making interventions available to patients and not forcing them to consume
      healthcare. One way of moving towards this would be to adopt a two-part decision
      process: the identification of the most cost-effective therapy using mean general
      population values (i.e. the current rule), then also making available those
      treatments that are cheaper than the most cost-effective therapy.

PMID- 19757865
TI  - Methods for measuring temporary health States for cost-utility analyses.
AB  - A variety of methods are available to measure preferences for temporary health
      states for cost-utility analyses. The objectives of this review were to summarize
      the available temporary health-state valuation methods, identify advantages and
      disadvantages of each, and identify areas for future research. We describe the
      key aspects of each method and summarize advantages and disadvantages of each
      method in terms of consistency with QALY theory, relevance to temporary health
      state-specific domains, ease of use, time preference, and performance in
      validation studies. Two broad categories of methods were identified: traditional
      and adapted. Traditional methods were health status instruments, time trade-off
      (TTO), and the standard gamble (SG). Methods adapted specifically for temporary
      health-state valuation were TTO with specified duration of the health state, TTO
      with a lifespan modification, waiting trade-off, chained approaches for TTO and
      SG, and sleep trade-off. Advantages and disadvantages vary by method and no 'gold
      standard' method emerged. Selection of a method to value temporary health states
      will depend on the relative importance of the following considerations: ability
      to accurately capture the unique characteristics of the temporary health state,
      level of respondent burden and cognition, theoretical consistency of elicited
      preference values with the overall purpose of the study, and resources available
      for study development and data collection. Further research should focus on
      evaluating validity, reliability and feasibility of temporary health-state
      valuation methods.

PMID- 19757866
TI  - Head lice treatments and school policies in the US in an era of emerging
      resistance: a cost-effectiveness analysis.
AB  - BACKGROUND: Head lice are a common infection in school-age children worldwide.
      Several authorities in the US have recommended different treatments and school
      policies in order to control this disease. Recent concerns of emerging lice
      resistance worldwide raise the necessity to reassess the current recommendations.
      OBJECTIVES: To perform a cost-effectiveness analysis (from the US caregiver
      perspective) of three head lice treatments commonly used in the US, permethrin
      1%, malathion 0.5% and the lice comb, in order to evaluate the cost effectiveness
      of different treatments in the current era, and to explore the effect of
      different factors in this analysis. METHODS: We used a decision-tree model to
      represent the costs and effectiveness of the different treatment strategies. A
      patient/caregiver perspective was applied, with a time horizon of 2 weeks.
      Probabilities of treatment success or failure of the three treatments were based
      on the literature. Effectiveness was measured as the successful eradication of
      head lice, and costs - including the costs of the treatment, the physician co-pay
      and the costs of days out of school - were calculated. One-way and multi-way
      analyses were performed using decision analysis software (Treeage Pro Healthcare
      2008). RESULTS: Combing was dominated by permethrin 1%. The incremental cost
      effectiveness ratio of malathion 0.5% versus permethrin 1% was $US161.75 per
      cure. For caregivers whose willingness to pay is <$US161.75 per cure, permethrin
      1% is the most cost-effective option. For those with a willingness to pay of > or
      =$US161.75 per cure malathion 1% may offer the highest net monetary benefit.
      Twenty percent of the uncertainty in the model is due to variation in permethrin
      1% resistance, and approximately 73% of the total variability of the model is
      attributed to the number of days the student has to be out of school because of
      the school's policy. CONCLUSIONS: Our study suggests that permethrin 1% was the
      most cost-effective treatment for those with a willingness to pay of <$US162 per
      cure. Sensitivity of lice to permethrin and the specific school head lice policy
      had major effects on the model. Thus, informing communities in a given
      geographical area about the degree of head lice resistance and sensitivity is
      necessary in order for the public to make a rational decision regarding
      treatment. Schools' head lice policies have a major effect on the cost of head
      lice treatments.

PMID- 19757867
TI  - A cost-effectiveness analysis to illustrate the impact of cost definitions on
      results, interpretations and comparability of pharmacoeconomic studies in the US.
AB  - BACKGROUND: There is a lack of a uniform proxy for defining direct medical costs
      in the US. This potentially important source of variation in modelling and other
      types of economic studies is often overlooked. The extent to which increased
      expenditures for an intervention can be offset by reductions in subsequent
      service costs can be directly related to the choice of cost definitions.
      OBJECTIVES: To demonstrate how different cost definitions for direct medical
      costs can impact results and interpretations of a cost-effectiveness analysis.
      METHODS: The IMS-CORE Diabetes Model was used to project the lifetime (35-year)
      cost effectiveness in the US of one pharmacological intervention 'medication A'
      compared with a second 'medication B' (both unspecified) for type 2 diabetes
      mellitus. The complications modelled included cardiovascular disease, renal
      disease, eye disease and neuropathy. The model had a Markov structure with Monte
      Carlo simulations. Utility values were derived from the published literature.
      Complication costs were obtained from a retrospective database study that
      extracted anonymous patient-level data from (primarily private payer) adjudicated
      medical and pharmaceutical claims. Costs for pharmacy services, outpatient
      services and inpatient hospitalizations were included. Cost definitions for
      complications included charged, allowed and paid amounts, and for medications
      included both wholesale acquisition cost (WAC) and average wholesale price (AWP).
      Costs were reported in year 2007 values. RESULTS: The cost-effectiveness results
      differed according to the particular combination of cost definitions employed.
      The use of charges greatly increased costs for complications. When the analysis
      incorporated WAC medication prices with charged amounts for complication costs,
      the incremental cost-effectiveness ratio (ICER) for medication A versus
      medication B was $US6337 per QALY. When AWP prices were used with charged
      amounts, medication A became a dominant treatment strategy, i.e. lower costs with
      greater effectiveness than medication B. For both allowed and paid scenarios,
      there was a difference in the ICER of over $US10,300 per QALY when medication
      prices were defined by WAC versus AWP. Ratios of medication costs to
      cardiovascular complication costs ranged from under 0.45 to over 1.7, depending
      upon the combination of costing definitions. CONCLUSIONS: Explicitly addressing
      the cost-definition issue can help provide meaningful cost-effectiveness data to
      payers for policy development and management of healthcare expenditures. It can
      also help move the pharmacoeconomics and outcomes research fields forward in
      terms of both methodology and practical application.

PMID- 19757868
TI  - Comparing three software tools for implementing markov models for health economic
      evaluations.
AB  - BACKGROUND: Various software packages are commonly used for the implementation
      and calculation of decision-analytic models for health economic evaluations.
      However, comparison of these programs with regard to ease of implementing a model
      is lacking. OBJECTIVES: (i) to compare the assets and drawbacks of three commonly
      used software packages for Markov models with regard to ease of implementation;
      and (ii) to investigate how a technical model validation can be conducted by
      comparing the results of the three implementations. METHODS: A Markov model on
      chronic obstructive pulmonary disease was implemented in TreeAge, Microsoft Excel
      and Arena with the same assumptions on model structure, transition probabilities
      and costs. A hypothetical smoking cessation programme for patients in stage 1 was
      evaluated against usual care. The packages were compared with respect to time and
      effort for implementation, run-time, features for the presentation of results,
      and flexibility. Agreement between the packages on average costs and life-years
      gained and on the incremental cost-effectiveness ratio was considered for
      technical validation in the form of expected values (between TreeAge and Excel
      only) and Monte Carlo simulations. RESULTS: Ease of implementation was best in
      TreeAge, whereas Arena offered the highest flexibility. Deterministic results
      were in agreement between TreeAge and Excel, as were simulated values between all
      three packages. CONCLUSIONS: Excel offers an intuitive spreadsheet interface, but
      the acquisition of and the training in TreeAge or Arena is worthwhile for more
      complex models. Double implementation is a practicable validation technique that
      should be conducted to ensure correct model implementation.

PMID- 19757869
TI  - The importance of clinical variables in comparative analyses using propensity
      score matching: the case of ESA costs for the treatment of chemotherapy-induced
      anaemia.
AB  - BACKGROUND: The erythropoiesis-stimulating agents (ESAs) epoetin alfa (EA) and
      darbepoetin alfa (DA) have comparable efficacy in treating chemotherapy-induced
      anaemia (CIA). Therapy choice depends on many factors, including cost. Previous
      estimates of ESA cost differences have been derived from claims data. These data
      lack clinical variables, such as baseline haemoglobin (Hb) level, which are
      likely to influence choice of ESA, dosing and costs. We estimated cost
      differences between DA and EA in patients with cancer receiving chemotherapy,
      using a propensity-score matched analysis of baseline patient characteristics
      with and without Hb values to assess the effect of this clinical variable on ESA
      cost estimates. METHODS: Data were extracted from electronic medical records in
      two US databases between January 2004 and December 2006. The study sample
      included 6743 patients receiving chemotherapy, with one or more visits during the
      study period, who received an ESA during a chemotherapy episode. Episodes of
      chemotherapy care were constructed using a 90-day gap in administration to
      identify the start and end. Patients receiving both DA and EA during their
      initial chemotherapy episode or with missing data were excluded, representing 42%
      of patients with CIA receiving an ESA. Drug costs were calculated from the
      cumulative dose multiplied by 106% of the average sales price (ASP) for DA or EA.
      Two propensity-score matches were conducted: first using variables available in
      administrative billing claims systems, then adding the baseline Hb test result.
      Regression-adjusted cost differences were estimated with and without baseline Hb,
      using generalized linear models. RESULTS: Using baseline Hb levels resulted in a
      better match of the baseline characteristics for the EA and DA treatment groups
      than the original sample or the matched sample without Hb variables. Mean ESA
      costs (year 2007 values) for the original sample were $US4171 for EA and $US3811
      for DA (mean difference $US360; p < 0.001, standard error [SE] $US99). With
      propensity-score matching without Hb variables, mean estimated costs were $US3836
      for EA and $US3599 for DA (mean difference $US237; p = 0.053, SE $US123). With
      propensity-score match including Hb variables, mean costs were $US3965 for EA and
      $US3536 for DA (mean difference $US429; p = 0.001, SE $US125). Cost differences
      in sensitivity analyses ranged between $US102 (p = 0.201) and $US261 (p = 0.003).
      CONCLUSIONS: Addition of baseline Hb level as a variable in propensity score and
      ESA cost models affects ESA treatment cost estimates in patients with cancer
      receiving chemotherapy. Cost comparisons based on observational data should use
      analytical methods that account for differences in clinical variables between
      treatment groups.

PMID- 19757870
TI  - Utilities of the EQ-5D: transferable or not?
AB  - BACKGROUND: Within the framework of economic evaluations, the transferability of
      utility scores between jurisdictions remains unclear. The EQ-5D is a generic
      instrument for measuring health-related quality of life in economic evaluations,
      which can be used for comparing utility scores across countries. At present, the
      EQ-5D has several national value sets or tariffs. Nevertheless, utility estimates
      from foreign studies are often used directly for cost-effectiveness estimates,
      without adapting by applying the appropriate national value set. It is unclear if
      this practice is advisable, due to dissimilarities between the national value
      sets. OBJECTIVES: To examine the effects of differences in national EQ-5D value
      sets on absolute and marginal utilities of health states, and determine to what
      degree these differences can be explained by methodological factors. METHODS:
      First, the relative importance of the EQ-5D domains for the utility estimates was
      compared across the 15 value sets. Second, two hypothetical health states for a
      depressed patient and a pain patient (21232 and 33321) were selected for
      additional analysis, by comparing the utilities as scored by the value sets. The
      marginal influence of a one-level deterioration in a domain of these health
      states on the utility estimate was then determined. Third, the differences
      between the value sets were examined in more detail by using multilevel analysis
      to examine the role of methodological differences in the valuation studies.
      RESULTS: Differences can be perceived between the national value sets of the EQ
      5D in the preferences for the domains. The utilities of the two hypothetical
      health states show that the value sets differ substantially. Furthermore, the
      differences between the marginal values of the deteriorations are large, which
      can be explained partly by the type of valuation method. Other methodological
      differences also influence the value sets. CONCLUSIONS: All results indicate that
      the differences between the EQ-5D value sets are considerable and should not be
      ignored. The differences can largely be explained by methodological differences
      in the valuation studies. The remaining differences may reflect cultural
      dissimilarities between countries. Therefore, further research should focus on
      investigating the transferability of utilities across countries or agreeing on a
      standard to perform valuation studies. For the time being, transferring utilities
      from one country to another without any adjustment is not advisable.

PMID- 19757871
TI  - Incremental 1-year medical resource utilization and costs for patients with
      herpes zoster from a set of US health plans.
AB  - BACKGROUND: Nearly 1 million new episodes of herpes zoster (HZ) occur annually in
      the US, yet little is known about the medical resource utilization (RU) and costs
      associated with HZ and its complications. OBJECTIVES: To describe the medical RU
      and cost burden of HZ in the first 90 days and the first year after diagnosis
      from the health insurer perspective and to stratify this burden for patients
      diagnosed with post-herpetic neuralgia (PHN) and those who are immunocompromised.
      In addition, this study explores costs from the societal perspective as a result
      of work loss in the first year after diagnosis. METHODS: The medical RU and cost
      data were obtained from the MarketScan Research Database for the years 1998-2003.
      This database contains inpatient, outpatient and prescription drug data for
      approximately 14 million individuals of all ages, covered under a variety of fee
      for-service and capitated provider reimbursement arrangements, including those
      with Medicare and private insurance. The work loss estimates were based on the
      MarketScan Health and Productivity Management Database. Claims for services
      incurred between 1 January 1998 and 31 December 2003 were screened to identify a
      cohort of HZ patients based on the presence of at least one International
      Classification of Diseases, 9th Revision (ICD-9) diagnosis code 053.xx. Each
      patient was assigned an index date based on the earliest observed occurrence of
      an HZ diagnosis. A cohort of PHN patients was identified as a subset of the HZ
      cohort with ICD-9 codes 053.12, 053.13, 053.19 or 729.2x in the period of 90 days
      to 12 months after the index date. Multivariable regression was used to compare
      HZ cases with matched controls after adjusting for demographic characteristics,
      insurance status, co-morbidities and medical expenditure in the 6 months prior to
      diagnosis for each of the endpoints. Separate regression models were developed,
      in which age and immune status were stratified. All costs were adjusted to March
      2008 values using the medical care component of the Consumer Price Index. The
      average per patient cost of all HZ cases was $US605 in the first 90 days after
      diagnosis and $US1052 at 1 year. For the subset with PHN, the average per patient
      cost of HZ at 1 year was $US3815. For the subset with an immunocompromising
      condition, the average HZ cost at 1 year was $US1745. The majority of the costs
      were the result of outpatient visits and prescription drugs. The subset of HZ
      cases that had both absence hour and short-term disability (STD) records
      available had 26.5 absence hours and 2.9 STD days. Healthcare utilization,
      medical care costs and work loss all increased with age for all HZ cases. Based
      on the results from the present study, the direct medical cost burden of HZ in
      the US is high, exceeding $US1000 per HZ patient. This direct medical cost may be
      nearly twice as high in immunocompromised patients and four times as high in the
      subset of HZ cases with PHN. The direct medical cost burden of HZ may exceed $US1
      billion annually in the US. The majority of medical RU and cost burden is
      incurred by the elderly. Although many people with HZ may no longer be in the
      workforce, HZ does contribute to lost work time.

PMID- 19757873
TI  - Castration of female ninespine stickleback by the pseudophyllidean cestode
      Schistocephalus pungitii: evolutionary significance and underlying mechanism.
AB  - Parasitic castration may result from manipulation of host energy allocation away
      from reproduction, which should result in castration of lightly infected hosts as
      well as heavily infected ones. Castration also may result from nutrient theft
      alone, which incidentally influences host energy allocation to reproduction and
      should cause reproduction to end in heavily infected hosts. Although the
      pseudophyllidean cestode Schistocephalus pungitii is a castrator of ninespine
      stickleback fish (Pungitius pungitius), the cause and significance of castration
      remain unknown. We used predictions about reproductive capacity in lightly and
      heavily infected hosts and host size (age) at which castration occurs to address
      these questions. In Airolo Lake, Alaska, we found that inhibition of reproduction
      in ninespine stickleback occurs in small fish before the size (age) of sexual
      maturity and is not instantaneous. Castration was observed in lightly and heavily
      infected adult-size hosts. Infected fish do not reach the same size as uninfected
      fish, possibly because of growth inhibition or selective predation. Castration in
      infected adult-size female ninespine stickleback appears to be the result of
      adaptive manipulation of host energy allocation by the parasite, but it could
      result from an energy budget readily influenced by parasitism.

PMID- 19757874
TI  - The effect of decibel level of music stimuli and gender on head circumference and
      physiological responses of premature infants in the NICU.
AB  - The purpose of this study was to examine different protocols with regard to the
      presentation of music stimuli and compare gender differential reactions to those
      stimuli. Subjects for this study (N = 63) were premature infants in the Neonatal
      Intensive Care Unit (NICU) between the gestational ages of 28 and 33 weeks. Half
      of the experimental infants listened to 20 mins of lullaby music (female voice
      with orchestral background) on 2 days followed by 20 mins of classical music
      (Mozart string music) on 2 days. The other half listened to the same music in the
      reverse order. One quarter of the males and one quarter of the females listened
      to music presented at an average of 65 dB, one quarter at an average of 70 dB,
      one quarter at an average of 75 dB, and one quarter did not listen to any music
      and served as control subjects. Head circumference data were collected four times
      by the researcher: (a) upon receipt of parental consent, (b) on the first day of
      music presentation (1 week after consent), (c) on the last day of music
      presentation, and (d) 1 week after music presentation. Physiological data (heart
      rate, respiratory rate, oxygen saturation) were recorded by the researcher at 2
      minute intervals starting 4 minutes prior to and ending 4 minutes after music
      presentation. There was a significant difference (p < .0001) in average daily
      head growth across time, but this seems unrelated to the music condition as the
      same curvilinear trend (larger gain during days of treatment, smaller gain during
      baseline before and after treatment) was noted for control infants who did not
      listen to music. Results indicate a significant (p = .002), but biologically
      unimportant, decrease in heart rate over the course of data collection. No
      differences due to gender were noted.

PMID- 19757875
TI  - The effects of music listening on inconsolable crying in premature infants.
AB  - Over the decades, medical staff have developed strategies to manage crying
      episodes of the critically ill and convalescing premature infant. These episodes
      of crying occur frequently after infants are removed from ventilation, but before
      they are able to receive nutrition orally. Not only are these episodes stressful
      to infants and upsetting to parents, but they are also stressful and time
      consuming for the staff that take care of these patients. Although the literature
      supports the benefits of music therapy in regard to physiological and certain
      behavioral measures with premature infants, no research exists that explores the
      use of music therapy with inconsolability related to the "nothing by mouth"
      status. This study explored the effects of music therapy on the crying behaviors
      of critically ill infants classified as inconsolable. Twenty-four premature
      infants with gestational age 32-40 weeks received a developmentally appropriate
      music listening intervention, alternating with days on which no intervention was
      provided. The results revealed a significant reduction in the frequency and
      duration of episodes of inconsolable crying as a result of the music
      intervention, as well as improved physiological measures including heart rate,
      respiration rate, oxygen saturation, and mean arterial pressure. Findings suggest
      the viability of using recorded music in the absence of a music therapist or the
      maternal voice to console infants when standard nursing interventions are not
      effective.

PMID- 19757876
TI  - Using the SCERTS model assessment tool to identify music therapy goals for
      clients with autism spectrum disorder.
AB  - The purposes of this paper were to identify and compare goals and objectives
      addressed by music therapists that are contained in the SCERTS Model, for use
      with children at risk or diagnosed with a communication impartment including
      Autism Spectrum Disorder (ASD). A video analysis of music therapists working with
      clients at risk or diagnosed with ASD (N = 33) was conducted to: (a) identify the
      areas of the SCERTS assessment model that music therapists are currently
      addressing within their sessions for clients with ASD, and (b) compare the
      frequency of SCERTS domains and goals addressed by music therapists within
      sessions. Results of the analysis revealed that all three domains of social
      communication, emotional regulation, and transactional support were addressed
      within music therapy sessions. Within each domain both broad goals were all
      addressed including joint attention and symbol use for social communication, self
      regulation and mutual regulation for emotional regulation, and interpersonal
      support and learning support for transactional support. Overall, music therapists
      addressed transactional support goals and subgoals more often than social
      communication and emotional regulation goals and subgoals. The highest frequency
      goal area addressed was interpersonal support (73.96%) and the lowest goal area
      addressed was joint attention (35.96%). For the social partner and language
      partner language stages, 58 of the 320 possible subgoals were addressed with 90%
      frequency or higher, while 13 of the same subgoals were never addressed. The
      SCERTS Model is designed for use by a multidisciplinary team of professionals and
      family members throughout a client's treatment and contains an ongoing assessment
      tool with resulting goals and objectives. This analysis indicates that many
      SCERTS goals and objectives can be addressed in music therapy interventions.
      Additionally, goals and subgoals not previously recognized in music therapy
      treatment can be generated by the use of the SCERTS Model.

PMID- 19757877
TI  - An examination of cue redundancy theory in cross-cultural decoding of emotions in
      music.
AB  - The present study investigated the effects of structural features of music (i.e.,
      variations in tempo, loudness, or articulation, etc.) and cultural and learning
      factors in the assignments of emotional meaning in music. Four participant
      groups, young Koreans, young Americans, older Koreans, and older Americans, rated
      emotional expressions of Korean folksongs with three adjective scales: happiness,
      sadness and anger. The results of the study are in accordance with the Cue
      Redundancy model of emotional perception in music, indicating that expressive
      music embodies both universal auditory cues that communicate the emotional
      meanings of music across cultures and cultural specific cues that result from
      cultural convention.

PMID- 19757878
TI  - Verticality and containment in song and improvisation: an application of schema
      theory to Nordoff-Robbins music therapy.
AB  - This study illustrates the use of a new musicological method for analyzing music
      in music therapy. It examines two pieces of clinical music through the constructs
      of schema theory. It begins with an argument for enhanced musical analysis in
      music therapy as a means of elevating the status of explanation in music therapy.
      Schema theory is introduced as a means of integrating musical with clinical
      concerns. Some basic ideas in schema theory are explained and the schemas of
      VERTICALITY and CONTAINER are presented as central ones in the analysis of music.
      Two transcriptions-one of a composed song and one of an improvisation-are
      examined in detail to illustrate how decisions in the temporal, melodic, and
      harmonic dimensions of the music are linked to specific clinical goals. The
      article concludes with a discussion of the implications of this type of
      musicological analysis for explanatory theory in music therapy.

PMID- 19757879
TI  - Gravity and observer's body orientation influence the visual perception of human
      body postures.
AB  - Since human behavior and perception have evolved within the Earth's gravitational
      field, humans possess an internal model of gravity. Although gravity is known to
      influence the visual perception of moving objects, the evidence is less clear
      concerning the visual perception of static objects. We investigated whether a
      visual judgment of the stability of human body postures (static postures of a
      human standing on a platform and tilted in the roll plane) may also be influenced
      by gravity and by the participant's orientation. Pictures of human body postures
      were presented in different orientations with respect to gravity and the
      participant's body. The participant's body was aligned to gravity (upright) or
      not (lying on one side). Participants performed stability judgments with respect
      to the platform, imagining that gravity operates in the direction indicated by
      the platform (that was or was not concordant with physical gravity). Such visual
      judgments were influenced by the picture's orientation with respect to physical
      gravity. When pictures were tilted by 90 degrees with respect to physical
      gravity, the human postures that were tilted toward physical gravity (down) were
      perceived as more unstable than similar postures tilted away from physical
      gravity (up). Stability judgments were also influenced by the picture's
      orientation with respect to the participant's body. This indicates that gravity
      and the participant's body position may influence the visual perception of static
      objects.

PMID- 19757880
TI  - Cross-orientation masking is speed invariant between ocular pathways but speed
      dependent within them.
AB  - In human (D. H. Baker, T. S. Meese, & R. J. Summers, 2007b) and in cat (B. Li, M.
      R. Peterson, J. K. Thompson, T. Duong, & R. D. Freeman, 2005; F. Sengpiel & V.
      Vorobyov, 2005) there are at least two routes to cross-orientation suppression
      (XOS): a broadband, non-adaptable, monocular (within-eye) pathway and a more
      narrowband, adaptable interocular (between the eyes) pathway. We further
      characterized these two routes psychophysically by measuring the weight of
      suppression across spatio-temporal frequency for cross-oriented pairs of
      superimposed flickering Gabor patches. Masking functions were normalized to
      unmasked detection thresholds and fitted by a two-stage model of contrast gain
      control (T. S. Meese, M. A. Georgeson, & D. H. Baker, 2006) that was developed to
      accommodate XOS. The weight of monocular suppression was a power function of the
      scalar quantity 'speed' (temporal-frequency/spatial-frequency). This weight can
      be expressed as the ratio of non-oriented magno- and parvo-like mechanisms,
      permitting a fast-acting, early locus, as benefits the urgency for action
      associated with high retinal speeds. In contrast, dichoptic-masking functions
      superimposed. Overall, this (i) provides further evidence for dissociation
      between the two forms of XOS in humans, and (ii) indicates that the monocular and
      interocular varieties of XOS are space/time scale-dependent and scale-invariant,
      respectively. This suggests an image-processing role for interocular XOS that is
      tailored to natural image statistics-very different from that of the scale
      dependent (speed-dependent) monocular variety.

PMID- 19757881
TI  - Attentional selection of noncontiguous locations: the spotlight is only
      transiently "split".
AB  - It is still a matter of debate whether observers can attend simultaneously to
      more than one location. Using essentially the same paradigm as was used
      previously by N. P. Bichot, K. R. Cave, and H. Pashler (1999), we demonstrate
      that their finding of an attentional "split" between separate target locations
      only reflects the early phase of attentional selection. Our subjects were asked
      to compare the shapes (circle or square) of 2 oddly colored targets within an
      array of 8 stimuli. After a varying stimulus onset asynchrony (SOA), 8 letters
      were flashed at the previous stimulus locations, followed by a mask. For a given
      SOA, the performance of subjects at reporting letters in each location was taken
      to reflect the distribution of spatial attention. In particular, by considering
      the proportion of trials in which none or both of the target letters were
      reported, we were able to infer the respective amount of attention allocated to
      each target without knowing, on a trial-by-trial basis which location (if any)
      was receiving the most attentional resources. Our results show that for SOAs
      under 100-150 ms, attention can be equally split between the two targets, a
      conclusion compatible with previous reports. However, with longer SOAs, this
      attentional division can no longer be sustained and attention ultimately settles
      at the location of one single stimulus.

PMID- 19757882
TI  - Simple differential latencies modulate, but do not cause the flash-lag effect.
AB  - When a brief static flash is presented in physical alignment with a moving
      target, the position of the flash can seem to lag behind that of the moving
      target. Various explanations exist. One of the most popular is the differential
      latency hypothesis. This assumes that neural latencies for moving stimuli are
      shorter than those for static stimuli. Accordingly, the flash lag would occur
      because perception is temporally fragmented, with moving stimuli seen before
      static. To test this, observers were asked to make different judgments concerning
      the same stimulus. Observers either judged if color changes in moving and static
      stimulus sections were synchronous, or whether the different stimulus sections
      were aligned at the time of a color change. If the flash-lag were driven by a
      simple differential latency, we would expect both judgments to be marked by a
      temporal advantage for moving stimuli. Our results suggest the contrary, as only
      the later judgment was marked by a flash-lag effect. The apparent timing of
      moving and static color changes was veridical. However, when we introduced a
      systematic differential latency, by modulating image contrast, both judgments
      were affected. Our data therefore suggest that a simple differential can modulate
      flash-lag type effects, but they do not cause the phenomenon.

PMID- 19757883
TI  - A study of N250 event-related brain potential during face and non-face detection
      tasks.
AB  - Face perception relies on activation of a complex set of different neural
      modules. In this study, we assessed the stimulus selectivity of the
      occipitotemporal N250 ERP component and the possible link between its neural
      substrates and modules underlying preceding (N170/VPP) and following (P400)
      category selective ERPs. We recorded N250 during face and leaf detection tasks
      while we varied stimulus visibility from trial to trial by using a backward
      masking paradigm. Our results revealed that N250, but not the other tested
      potentials, was exclusively sensitive to the visibility of faces even when the
      non-face stimuli served as the task target. We also found a correlation between
      evoked N170 and N250, in response to face stimuli and to a lesser extent in
      response to other non-face objects, irrespective of the subjects' task. Besides
      N250, P400 also showed a strong correlation with N170, but here, the amount of
      correlation was not affected by stimulus category. Interestingly, despite N250
      and N400 correlation with N170, we did not find any correlation between N250 and
      P400, suggesting that modules underlying these ERP components belong to two
      different face-processing pathways. We suggest that N250 is initiated by N170 and
      indexes processes exclusively responsible for encoding faces.

PMID- 19757884
TI  - Visual performance after correcting higher order aberrations in keratoconic eyes.
AB  - Keratoconic eyes are affected by an irregular optical blur induced by significant
      magnitude of higher order aberrations (HOAs). Although it is expected that
      correction of ocular aberrations leads to an improvement in visual performance,
      keratoconic eyes might not achieve the visual benefit predicted by optical theory
      because of long-term adaptation to poor retinal image quality. To investigate
      this, an adaptive optics (AO) system equipped with a large-stroke deformable
      mirror and a Shack-Hartmann wavefront sensor was used to correct the aberrations
      and measure high contrast tumbling E visual acuity (HCVA) in 8 keratoconic eyes.
      Eight normal eyes were employed as control. Aberrations were dynamically
      corrected with closed-loop AO during visual acuity testing, with residual root
      mean-square error of around 0.1 microm in both groups over 6-mm pupil (p = 0.11).
      With AO correction, the HCVA in logMAR was -0.26 +/- 0.063 in normal eyes, and in
      keratoconic eyes, it was -0.07 +/- 0.051 (p = 0.0001) for the same pupil size.
      There was no correlation in the AO-corrected HCVA for normals with the magnitudes
      of their native HOA. However, within keratoconic eyes, poorer AO-corrected HCVA
      was observed with an increase of the native magnitudes of HOA (R(2) = 0.67). This
      may indicate that long-term visual experience with poor retinal image quality,
      induced by HOA, may restrict the visual benefit achievable immediately after
      correction in keratoconic eyes.

PMID- 19757885
TI  - Center-surround patterns emerge as optimal predictors for human saccade targets.
AB  - The human visual system is foveated, that is, outside the central visual field
      resolution and acuity drop rapidly. Nonetheless much of a visual scene is
      perceived after only a few saccadic eye movements, suggesting an effective
      strategy for selecting saccade targets. It has been known for some time that
      local image structure at saccade targets influences the selection process.
      However, the question of what the most relevant visual features are is still
      under debate. Here we show that center-surround patterns emerge as the optimal
      solution for predicting saccade targets from their local image structure. The
      resulting model, a one-layer feed-forward network, is surprisingly simple
      compared to previously suggested models which assume much more complex
      computations such as multi-scale processing and multiple feature channels.
      Nevertheless, our model is equally predictive. Furthermore, our findings are
      consistent with neurophysiological hardware in the superior colliculus. Bottom-up
      visual saliency may thus not be computed cortically as has been thought
      previously.

PMID- 19757886
TI  - Characterizing global and local mechanisms in biological motion perception.
AB  - The perception of biological motion is subserved by both a global process that
      retrieves structural information and a local process that is sensitive to
      individual limb motions. Here, we present an experiment aimed to characterize
      these two mechanisms psychophysically. Naive observers were tested on one of two
      tasks. In a walker detection task designed to address global processing,
      observers were asked to discriminate coherent from scrambled walkers presented in
      separate intervals. In an alternate direction discrimination task designed to
      address primarily local processing, observers were asked to discriminate walking
      direction from both coherent and spatially scrambled displays. In both tasks, we
      investigated performance-specificity to human (versus non-human) motion and the
      effects of mask density and learning on task performance. Performance in the
      walker detection task was best for the human walker, was susceptible to learning,
      and was heavily hindered by increasing mask densities. In contrast, performance
      on the direction discrimination task, in particular for the scrambled walkers,
      was unaffected by walker type, did not show a learning trend, and was relatively
      robust to masking noise. These findings suggest that the visual system processes
      global and local information contained in biological motion via distinct neural
      mechanisms that have very different properties.

PMID- 19757887
TI  - Low-level mechanisms may contribute to paradoxical motion percepts.
AB  - A recent series of experiments demonstrated a surprising deterioration of visual
      motion discrimination with increasing stimulus size for stimuli of high contrast.
      This counterintuitive finding was explained as a result of surround suppression
      in visual area V5. Equally paradoxical was the finding that older observers
      showed better performance than younger observers. This second result was
      explained as an age-related reduction in surround suppression due to changes in
      GABA-mediated inhibition. Using an opponent motion stimulus, we find an analogous
      effect and also find that this effect is much reduced in older observers, to the
      point where they perform better than younger observers. Our long duration
      stimulus should be beyond the range at which surround-suppressed neurons in V5
      are preferentially activated. Having normalized our stimuli relative to contrast
      threshold, we show that our results can be entirely explained by the relative
      contrast of the stimulus and speculate that contrast sensitivity may play a role
      in previously reported results. Our older observers' data similarly can be
      explained by the relative contrast of the stimulus. The difference between older
      and younger observers appears to be a result of a weakening of spatial summation
      at high contrast in younger observers, perhaps caused by earlier saturation of
      motion mechanisms.

PMID- 19757888
TI  - Motion streaks in fast motion rivalry cause orientation-selective suppression.
AB  - We studied binocular rivalry between orthogonally translating arrays of random
      Gaussian blobs and measured the strength of rivalry suppression for static
      oriented probes. Suppression depth was quantified by expressing monocular probe
      thresholds during dominance relative to thresholds during suppression. Rivalry
      between two fast motions or two slow motions was compared in order to test the
      suggestion that fast-moving objects leave oriented "motion streaks" due to
      temporal integration (W. S. Geisler, 1999). If fast motions do produce motion
      streaks, then fast motion rivalry might also entail rivalry between the
      orthogonal streak orientations. We tested this using a static oriented probe that
      was aligned either parallel to the motion trajectory (hence collinear with the
      "streaks") or was orthogonal to the trajectory, predicting that rivalry
      suppression would be greater for parallel probes, and only for rivalry between
      fast motions. Results confirmed that suppression depth did depend on probe
      orientation for fast motion but not for slow motion. Further experiments showed
      that threshold elevations for the oriented probe during suppression exhibited
      clear orientation tuning. However, orientation-tuned elevations were also present
      during dominance, suggesting within-channel masking as the basis of the extra
      deep suppression. In sum, the presence of orientation-dependent suppression in
      fast motion rivalry is consistent with the "motion streaks" hypothesis.

PMID- 19757889
TI  - Aging alters surround modulation of perceived contrast.
AB  - It is well established that many visual functions deteriorate with age. Perhaps
      counter-intuitively, a recent study revealed that older people actually require
      less time to discriminate the direction of motion of large, high contrast moving
      stimuli than young adults (L. R. Betts, C. P. Taylor, A. B. Sekuler, & P. J.
      Bennett, 2005). L. R. Betts et al. (2005) proposed their finding as evidence for
      a reduction of cortical inhibitory function within the aging visual system. There
      is some neurophysiological support for this suggestion, as broadening of visual
      cortical neural tuning consistent with reduced inhibitory function has been
      observed in older animals. Here we explore the perceptual consequences of center
      surround suppression within the healthy aging human visual system and report data
      from a center-surround contrast discrimination task (the Chubb contrast
      illusion). We predicted that older observers would demonstrate less center
      surround suppression than younger subjects (consistent with reduced inhibition).
      Our data does not support this prediction as perceived contrast was altered more
      by surround modulation in the older than younger group (t(33) = 2.53, p = 0.02).
      A possible explanation for our findings is a decrease in perceptual brightness
      induction in the elderly group. Brightness induction relies on neural
      synchronization which might be disrupted by aging.

PMID- 19757890
TI  - Is the early modulation of brain activity by fearful facial expressions primarily
      mediated by coarse low spatial frequency information?
AB  - Rapidly decoding the emotional content of a face is an important skill for
      successful social behavior. Several Event Related brain Potential (ERP) have
      indicated that emotional expressions already influence brain activity as early as
      100 ms. Some studies hypothesized that this early brain response to fear depends
      on coarse-magnocellular inputs, which are primarily driven by Low Spatial
      Frequency (LSF) cues. Until now however, evidence is inconclusive probably due to
      the divergent methods used to match luminance and contrast across spatial
      frequencies and emotional stimuli. In the present study, we measured ERPs to LSF
      and HSF faces with fearful or neutral expressions when contrast and luminance was
      matched across SF or not. Our findings clearly show that fearful facial
      expressions increases the amplitude of P1 (only for contrast-luminance equated
      images) and N170 in comparison to neutral faces but only in LSF faces,
      irrespective of contrast or luminance equalization, further suggesting that LSF
      information plays a crucial role in the early brain responses to fear.
      Furthermore, we found that, irrespective of luminance or contrast equalization,
      N170 occurred faster when perceiving LSF faces than HSF faces, again emphasizing
      the primacy of LSF processing in early face perception.

PMID- 19757891
TI  - Asymmetric interference between the perception of shape and the perception of
      surface properties.
AB  - We previously showed that the processing of shape and the processing of surface
      properties linked to material properties engage different regions of the ventral
      stream (J. S. Cant & M. A. Goodale, 2007). Moreover, we recently used Garner's
      speeded-classification task to show that varying the surface (material)
      properties of objects does not interfere with shape judgments and vice versa (J.
      S. Cant, M. E. Large, L. McCall, & M. A. Goodale, 2008). In the present study, we
      looked at Garner interference when surface cues contributed to the perception of
      object shape and hypothesized that this would interfere with judgments about the
      width and the length of the objects. In contrast, we predicted that varying the
      width and the length of the objects would not interfere with surface-property
      judgments. This is precisely what we found. These results suggest that the shape
      and the surface properties of an object cannot be processed independently when
      both these sets of cues are linked to the perception of the object's overall
      shape. These observations, together with our previous findings, suggest that the
      surface cues that contribute to object shape are processed quite separately from
      the surface cues that are linked to an object's material properties.

PMID- 19757892
TI  - Color and shape interactions in the recognition of natural scenes by human and
      monkey observers.
AB  - Trichromatic color vision is a fundamental aspect of the visual system shared by
      humans and non-human primates. In human observers, color has been shown to
      facilitate object identification. However, little is known about the role that
      color plays in higher level vision of non-human primates. Here, we addressed this
      question and studied the interaction between luminance- and color-based
      structural information for the recognition of natural scenes. We present
      psychophysical data showing that both monkey and human observers equally profited
      from color when recognizing natural scenes, and they were equally impaired when
      scenes were manipulated using colored noise. This effect was most prominent for
      degraded image conditions. By using a specific procedure for stimulus
      degradation, we found that the improvement as well as the impairment in visual
      memory performance is due to contribution of image color independent of luminance
      based object information. Our results demonstrate that humans as well as non
      human primates exploit their sensory ability of color vision to achieve higher
      performance in visual recognition tasks especially when shape features are
      degraded.

PMID- 19757893
TI  - Optimal feature integration in visual search.
AB  - Despite embodying fundamentally different assumptions about attentional
      allocation, a wide range of popular models of attention include a max-of-outputs
      mechanism for selection. Within these models, attention is directed to the items
      with the most extreme-value along a perceptual dimension via, for example, a
      winner-take-all mechanism. From the detection theoretic approach, this MAX
      observer can be optimal under specific situations, however in distracter
      heterogeneity manipulations or in natural visual scenes this is not always the
      case. We derive a Bayesian maximum a posteriori (MAP)-observer, which is optimal
      in both these situations. While it retains a form of the max-of-outputs
      mechanism, it is based on the maximum a posterior probability dimension, instead
      of a perceptual dimension. To test this model we investigated human visual search
      performance using a yes/no procedure while adding external orientation
      uncertainty to distracter elements. The results are much better fitted by the
      predictions of a MAP observer than a MAX observer. We conclude a max-like
      mechanism may well underlie the allocation of visual attention, but this is based
      upon a probability dimension, not a perceptual dimension.

PMID- 19757894
TI  - The reference frame of the motion aftereffect is retinotopic.
AB  - Although eye-, head- and body-movements can produce large-scale translations of
      the visual input on the retina, perception is notable for its spatiotemporal
      continuity. The visual system might achieve this by the creation of a detailed
      map in world coordinates--a spatiotopic representation. We tested the coordinate
      system of the motion aftereffect by adapting observers to translational motion
      and then tested (1) at the same retinal and spatial location (full aftereffect
      condition), (2) at the same retinal location, but at a different spatial location
      (retinotopic condition), (3) at the same spatial, but at a different retinal
      location (spatiotopic condition), or (4) at a different spatial and retinal
      location (general transfer condition). We used large stimuli moving at high speed
      to maximize the likelihood of motion integration across space. In a second
      experiment, we added a contrast-decrement detection task to the motion stimulus
      to ensure attention was directed at the adapting location. Strong motion
      aftereffects were found when observers were tested in the full and retinotopic
      aftereffect conditions. We also found a smaller aftereffect at the spatiotopic
      location but it did not differ from that at the location that was neither
      spatiotopic nor retinotopic. This pattern of results did not change when
      attention was explicitly directed at the adapting stimulus. We conclude that
      motion adaptation took place at retinotopic levels of visual cortex and that no
      spatiotopic interaction of motion adaptation and test occurred across saccades.

PMID- 19757895
TI  - Temporal structure of chromatic channels revealed through masking.
AB  - The human color and luminance-driven systems appear to be mediated by mechanisms
      with distinct spatio-temporal tuning properties, with the iso-luminant color
      driven system comparatively less sensitive to high rates of temporal modulation.
      While color and luminance defined speed and rate discrimination studies indicate
      perceptual access to the outputs of multiple, overlapping temporal frequency
      selective mechanisms (channels), a detailed functional characterization of their
      response is currently restricted to the luminance-driven domain. Threshold
      elevations for 1- and 10-Hz targets were measured as a function of the temporal
      frequency of a spatio-temporally overlaid masking stimulus (1-30 Hz). Target and
      masking stimuli were iso-oriented gratings spatio-temporally modulated along each
      axis of human color space: L - M (red-green), S + S- (violet-yellow; S-cone
      isolating), and L + M + S (achromatic). Qualitatively equivalent patterns of
      temporal frequency-dependent masking were observed when measured within and, with
      one exception (red-green target, achromatic mask), between cardinal axes of human
      color space: fitted by one low-pass and one bandpass Gaussian function. That both
      low-pass and higher bandpass masking functions were evident between iso-luminant
      cardinal color axes (L - M and S + S-) suggests that both low and high temporal
      frequency masking may be cortically mediated.

PMID- 19757896
TI  - Identity processing in multiple-face tracking.
AB  - Research has shown that observers in a multiple-object tracking task are poor at
      recognizing the identity of successfully tracked objects (Z. W. Pylyshyn, 2004).
      Employing the same paradigm, we examined identity processing and its relationship
      with tracking performance for human faces. Experiment 1 showed that although
      identity recognition was poorer after the target faces were learned in a dynamic
      display, identification performance was still much higher than the chance level.
      The experiment also found that on average about two face identities can be
      correctly traced to their locations. Experiment 2 showed that tracking
      performance decreased significantly for unique upright faces relative to the
      unique inverted or identical upright faces, suggesting that upright faces
      activate some level of mandatory identity processing that interferes and competes
      with visual tracking for attentional resources. Experiment 3 found that only
      target faces receive identity processing in the tracking task. Experiment 4
      showed that switching face identities during tracking impaired tracking
      performance. This may indicate that identity encoding is to some extent
      obligatory during multiple-face tracking. Furthermore, Experiment 5 suggested
      that attentional resources can be consciously allocated either to maximize
      identity encoding or tracking, resulting in a tradeoff between the two. The
      results reveal a bias for face identity processing, which may differ
      significantly from multiple-object tracking.

PMID- 19757897
TI  - Free viewing of dynamic stimuli by humans and monkeys.
AB  - Due to extensive homologies, monkeys provide a sophisticated animal model of
      human visual attention. However, for electrophysiological recording in behaving
      animals simplified stimuli and controlled eye position are traditionally used. To
      validate monkeys as a model for human attention during realistic free viewing, we
      contrasted human (n = 5) and monkey (n = 5) gaze behavior using 115 natural and
      artificial video clips. Monkeys exhibited broader ranges of saccadic endpoints
      and amplitudes and showed differences in fixation and intersaccadic intervals. We
      compared tendencies of both species to gaze toward scene elements with similar
      low-level visual attributes using two computational models--luminance contrast
      and saliency. Saliency was more predictive of both human and monkey gaze,
      predicting human saccades better than monkey saccades overall. Quantifying
      interobserver gaze consistency revealed that while humans were highly consistent,
      monkeys were more heterogeneous and were best predicted by the saliency model. To
      address these discrepancies, we further analyzed high-interest gaze targets-
      those locations simultaneously chosen by at least two monkeys. These were on
      average very similar to human gaze targets, both in terms of specific locations
      and saliency values. Although substantial quantitative differences were revealed,
      strong similarities existed between both species, especially when focusing
      analysis onto high-interest targets.

PMID- 19757898
TI  - Comparing eye movements to detected vs. undetected target stimuli in an Identity
      Search task.
AB  - Why do we perceive some elements in a visual scene, while others remain
      undetected? To learn about the sequence of events leading to detection, we
      directly compared fixations on detected vs. undetected items. Our novel Identity
      Search task display comprised twelve cards, all different except for two pairs of
      identical cards. Participants search for one pair. Task properties allow us to
      monitor fixations on distinct card regions and study search dynamics. We find
      that detected pair cards were fixated more often and for longer times than
      undetected pair cards. Within the search sequence, there are fewer intervening
      fixations between detected than undetected pair cards. Only at an advanced stage
      of the search do fixations on pair cards become closer. We suggest that both the
      absolute number of fixations and their temporal proximity influence detection. In
      the dynamics of search, a bifurcation point is observed, when these differential
      characteristics begin. Analysis of the break point in the sequence of fixations
      on to-be-detected cards suggests that there is an early--perhaps unconscious-
      recognition stage, followed by more fixations and only later by detection. We
      suggest that several target fixations are needed for processing visual
      information to achieve recognition.

PMID- 19757899
TI  - The effect of notched noise on flicker detection and discrimination.
AB  - Flicker perception was investigated using two-alternative forced-choice detection
      and discrimination tasks with four different types of external noise: (1)
      broadband noise, (2) 5-Hz notched-noise--broadband noise with a 5-Hz band
      centered on the signal frequency removed, (3) 10-Hz notched-noise, and (4) no
      external noise. The signal was a burst of 10-Hz sinusoidal flicker presented in
      one of two observation intervals. In discrimination experiments, a pedestal-
      sinusoidal flicker with the same frequency, duration, and phase as the signal-
      was added to both observation intervals. With no noise, observers' performance
      first improved with increasing pedestal modulation, before deteriorating in
      accordance with Weber's Law, producing the typical "dipper" shaped plot of signal
      versus pedestal modulation. Noise affects performance, but the dipper effect
      persisted in each type of noise. The results exclude three models: the ideal
      observer in which the pedestal improves performance by specifying the signal
      exactly; off-frequency-looking models in which the dipper depends on detection by
      channels tuned to temporal frequencies different from that of the signal; and
      strict energy detectors. Our data are consistent with signal processing by a
      single mechanism with an expansive non-linearity for near-threshold signal
      modulations (with an exponent of six) and a compressive "Weberian" non-linearity
      for high modulations.

PMID- 19757900
TI  - Daily mixed visual experience that prevents amblyopia in cats does not always
      allow the development of good binocular depth perception.
AB  - Kittens reared with mixed daily visual input that consists of episodes of normal
      (binocular) exposure followed by abnormal (monocular) exposure can develop normal
      visual acuity in both eyes if the length of the former exposure exceeds a
      critical amount. However, later studies of the tuning of cells in primary visual
      cortex of animals reared in this manner revealed that their responses to
      interocular differences in phase were not reliable suggesting that their
      binocular depth perception may not be normal. We examined this possibility in 3
      kittens reared with mixed daily visual exposure (2 hrs binocular vision followed
      by 5 hrs monocular exposure) that allowed development of normal visual acuity in
      both eyes. Measurements made of the threshold differences in depth that could be
      perceived under monocular and binocular viewing revealed a 10-fold superiority of
      binocular over monocular depth thresholds in one animal while the depth
      thresholds of the other two animals were poor and there was no binocular
      superiority. Thus, there was evidence that only one animal possessed stereopsis
      while the other two were likely stereoblind. While 2 hrs of daily binocular
      vision protected against the development of amblyopia, the poor outcome with
      respect to stereopsis points to the need for additional measures to promote
      binocular vision.

PMID- 19757901
TI  - Bayesian priors are encoded independently from likelihoods in human multisensory
      perception.
AB  - It has been shown that human combination of crossmodal information is highly
      consistent with an optimal Bayesian model performing causal inference. These
      findings have shed light on the computational principles governing crossmodal
      integration/segregation. Intuitively, in a Bayesian framework priors represent a
      priori information about the environment, i.e., information available prior to
      encountering the given stimuli, and are thus not dependent on the current
      stimuli. While this interpretation is considered as a defining characteristic of
      Bayesian computation by many, the Bayes rule per se does not require that priors
      remain constant despite significant changes in the stimulus, and therefore, the
      demonstration of Bayes-optimality of a task does not imply the invariance of
      priors to varying likelihoods. This issue has not been addressed before, but here
      we empirically investigated the independence of the priors from the likelihoods
      by strongly manipulating the presumed likelihoods (by using two drastically
      different sets of stimuli) and examining whether the estimated priors change or
      remain the same. The results suggest that the estimated prior probabilities are
      indeed independent of the immediate input and hence, likelihood.

PMID- 19757902
TI  - Pulfrich phenomena are coded effectively by a joint motion-disparity process.
AB  - Pulfrich phenomena are a class of depth illusions generated by an interocular
      time delay. This may be demonstrated with continuously moving stimuli,
      stroboscopic displays undergoing apparent motion, or dynamic noise patterns.
      Previous studies suggest that neurons jointly tuned to motion and disparity may
      be responsible for the phenomena. Model cells with such joint coding can explain
      all Pulfrich phenomena in a unified way (N. Qian & R. A. Andersen, 1997).
      However, the joint-coding idea has been challenged by recent models (J. C. Read &
      B. G. Cumming, 2005a, 2005c) that focus on the S shaped functions of perceived
      disparity in stroboscopic Pulfrich effect (M. J. Morgan, 1979). Here we
      demonstrate fundamental problems with the recent models in terms of causality,
      physiological plausibility, and definitions for joint and separate coding, and we
      compare the two coding schemes under physiologically plausible assumptions. We
      show that joint coding of disparity and either unidirectional or bidirectional
      motion selectivity can account for the S curves, but unidirectional selectivity
      is required to explain direction-depth contingency in Pulfrich effects. In
      contrast, separate coding can explain neither the S curves nor the direction
      depth contingency. We conclude that Pulfrich phenomena are logically accounted
      for by joint encoding of unidirectional-motion and disparity.

PMID- 19757903
TI  - A model of top-down attentional control during visual search in complex scenes.
AB  - Recently, there has been great interest among vision researchers in developing
      computational models that predict the distribution of saccadic endpoints in
      naturalistic scenes. In many of these studies, subjects are instructed to view
      scenes without any particular task in mind so that stimulus-driven (bottom-up)
      processes guide visual attention. However, whenever there is a search task, goal
      driven (top-down) processes tend to dominate guidance, as indicated by attention
      being systematically biased toward image features that resemble those of the
      search target. In the present study, we devise a top-down model of visual
      attention during search in complex scenes based on similarity between the target
      and regions of the search scene. Similarity is defined for several feature
      dimensions such as orientation or spatial frequency using a histogram-matching
      technique. The amount of attentional guidance across visual feature dimensions is
      predicted by a previously introduced informativeness measure. We use eye-movement
      data gathered from participants' search of a set of naturalistic scenes to
      evaluate the model. The model is found to predict the distribution of saccadic
      endpoints in search displays nearly as accurately as do other observers' eye
      movement data in the same displays.

PMID- 19757904
TI  - The neural pathways mediating color shifts induced by temporally varying light.
AB  - In natural viewing, an object's background often changes over time. Temporally
      varying backgrounds were investigated here with a steady test field within a time
      varying surrounding chromaticity. With slow surround variation (below
      approximately 3 Hz), the color appearance of a steady test is also perceived to
      fluctuate. At somewhat higher temporal frequencies, however, temporal variation
      of the surround is visible but the test appears steady (R. L. De Valois, M. A.
      Webster, K. K. De Valois, & B. Lingelbach, 1986); also above approximately 3 Hz,
      temporal chromatic variation along the l- or s-axis of the MacLeod-Boynton space
      (symmetric about equal-energy-spectrum "white") shifts the steady appearance of
      the test field toward redness or yellowness, respectively (A. D. D'Antona & S. K.
      Shevell, 2006). In the study here, color shifts were measured with temporal
      surround modulation at 6 Hz or greater along axes intermediate to the l and s
      directions. Varying the relative phase of simultaneous surround variation in l
      and s should not change responses within independent l and s pathways but should
      differentially excite neural representations that combine l and s signals (so
      called higher order chromatic mechanisms). Varying the phase of l and s showed
      that the induced color shifts were accounted for by neural responses both from
      nearly independent l and s pathways and from higher order chromatic mechanisms.

PMID- 19757905
TI  - Figure-ground assignment to a translating contour: a preference for advancing vs.
      receding motion.
AB  - Past research on figure-ground assignment to contours has largely considered
      static stimuli. Here we report a simple and extremely robust dynamic cue to
      figural assignment, based on whether the bounding region of a contour is growing
      larger within the field of view ("advancing") rather than smaller ("receding").
      Subjects viewed a straight or jagged contour dividing two colored regions
      translating behind a virtual aperture and had to report which color they had seen
      "moving in front", effectively assigning figure to that side of the contour.
      Across three experiments, subjects showed a strong preference to assign figure
      such that the bounded contour was advancing. This was true regardless of the
      direction of motion of the contour and regardless of the initial/ending size of
      the bounded regions (i.e., the motion cue served to override the conventional cue
      to figure-ground of smaller area). In a fourth, control experiment, subjects
      showed no such bias when it was the aperture, rather than the contour, that
      moved, demonstrating that the effect depends on contour motion and not simply an
      increase in area. We discuss a possible explanation for this bias as well as the
      general implications regarding dynamic factors in form perception.

PMID- 19757906
TI  - Combination of noisy directional visual and proprioceptive information.
AB  - We present experimental and computational evidence for the estimation of visual
      and proprioceptive directional information during forward, visually driven arm
      movements. We presented noisy directional proprioceptive and visual stimuli
      simultaneously and in isolation midway during a pointing movement. Directional
      proprioceptive stimuli were created by brief force pulses, which varied in
      direction and were applied to the fingertip shortly after movement onset.
      Subjects indicated the perceived direction of the stimulus after each trial. We
      measured unimodal performance in trials in which we presented only the visual or
      only the proprioceptive stimulus. When we presented simultaneous but conflicting
      bimodal information, subjects' perceived direction fell in between the visual and
      proprioceptive directions. We find that the judged mean orientation matched the
      MLE predictions but did not show the expected improvement in reliability as
      compared to unimodal performance. We present an alternative model (probabilistic
      cue switching, PCS), which is consistent with our data. According to this model,
      subjects base their bimodal judgments on only one of two directional cues in a
      given trial, with relative choice probabilities proportional to the average
      stimulus reliability. These results suggest that subjects based their decision on
      a probability mixture of both modalities without integrating information across
      modalities.

PMID- 19757907
TI  - Post-saccadic location judgments reveal remapping of saccade targets to non
      foveal locations.
AB  - The present study addresses the question of how objects are localized across
      saccades. In a task requiring participants to compare the location of a post
      saccadic probe with the pre-saccadic target, we investigated the roles of saccade
      landing site and post-saccadic probe location. Saccade landing sites vary from
      trial to trial because of oculomotor error but can also be shifted by saccadic
      adaptation. Visual targets were extinguished during the saccade and reappeared
      after a short blank to counteract saccadic suppression of displacement.
      Performance in localizing targets after unadapted saccades was nearly veridical
      and independent of actual landing site, showing that trial-to-trial oculomotor
      error did not contribute to post-saccadic localization. This result suggests that
      much of the oculomotor error of saccades is included in the efference copy vector
      and this allows the recovery of a remapped target location that is often not
      foveal, but stable and accurate across trials. Displacement judgments relative to
      this remapped location will be independent of trial-to-trial variability in
      landing site. After adapted saccades, post-saccadic localization shifted in the
      direction opposite to adaptation but again, trial-by-trial landing site
      variability did not correlate with performance. This result suggests that the
      efference copy matches the planned upcoming saccade, be it adapted or not.

PMID- 19757908
TI  - Motion mechanisms with different spatiotemporal characteristics identified by an
      MAE technique with superimposed gratings.
AB  - We investigated spatiotemporal characteristics of motion mechanisms using a new
      type of motion aftereffect (MAE) we found. Our stimulus comprised two
      superimposed sinusoidal gratings with different spatial frequencies. After
      exposure to the moving stimulus, observers perceived the MAE in the static test
      in the direction opposite to that of the high spatial frequency grating even when
      low spatial frequency motion was perceived during adaptation. In contrast, in the
      flicker test, the MAE was perceived in the direction opposite to that of the low
      spatial frequency grating. These MAEs indicate that two different motion systems
      contribute to motion perception and can be isolated by using different test
      stimuli. Using a psychophysical technique based on the MAE, we investigated the
      differences between the two motion mechanisms. The results showed that the static
      MAE is the aftereffect of the motion system with a high spatial and low temporal
      frequency tuning (slow motion detector) and the flicker MAE is the aftereffect of
      the motion system with a low spatial and high temporal frequency tuning (fast
      motion detector). We also revealed that the two motion detectors differ in
      orientation tuning, temporal frequency tuning, and sensitivity to relative
      motion.

PMID- 19757909
TI  - An examination of binocular reading fixations based on sentence corpus data.
AB  - Binocular eye movements of normal adult readers were examined as they read single
      sentences. Analyses of horizontal and vertical fixation disparities indicated
      that the most prevalent type of disparate fixation is crossed (i.e., the left eye
      is located further to the right than the right eye) while the left eye frequently
      fixates somewhat above the right eye. The Gaussian distribution of the binocular
      fixation point peaked 2.6 cm in front of the plane of text, reflecting the
      prevalence of horizontally crossed fixations. Fixation disparity accumulates
      during the course of successive saccades and fixations within a line of text, but
      only to an extent that does not compromise single binocular vision. In reading,
      the version and vergence system interact in a way that is qualitatively similar
      to what has been observed in simple nonreading tasks. Finally, results presented
      here render it unlikely that vergence movements in reading aim at realigning the
      eyes at a given saccade target word.

PMID- 19757910
TI  - Demand-based dynamic distribution of attention and monitoring of velocities
      during multiple-object tracking.
AB  - The ability to track multiple moving objects with attention has been the focus of
      much research. However, the literature is relatively inconclusive regarding two
      key aspects of this ability, (1) whether the distribution of attention among the
      tracked targets is fixed during a period of tracking or is dynamically adjusted,
      and (2) whether motion information (direction and/or speed) is used to anticipate
      target locations even when velocities constantly change due to inter-object
      collisions. These questions were addressed by analyzing target-localization
      errors. Targets in crowded situations (i.e., those in danger of being lost) were
      localized more precisely than were uncrowded targets. Furthermore, the response
      vector (pointing from the target location to the reported location) was tuned to
      the direction of target motion, and observers with stronger direction tuning
      localized targets more precisely. Overall, our results provide evidence that
      multiple-object tracking mechanisms dynamically adjust the spatial distribution
      of attention in a demand-based manner (allocating more resources to targets in
      crowded situations) and utilize motion information (especially direction
      information) to anticipate target locations.

PMID- 19757911
TI  - Biological "bar codes" in human faces.
AB  - The structure of the human face allows it to signal a wide range of useful
      information about a person's gender, identity, mood, etc. We show empirically
      that facial identity information is conveyed largely via mechanisms tuned to
      horizontal visual structure. Specifically observers perform substantially better
      at identifying faces that have been filtered to contain just horizontal
      information compared to any other orientation band. We then show,
      computationally, that horizontal structures within faces have an unusual tendency
      to fall into vertically co-aligned clusters compared with images of natural
      scenes. We call these clusters "bar codes" and propose that they have important
      computational properties. We propose that it is this property makes faces
      "special" visual stimuli because they are able to transmit information as
      reliable spatial sequence: a highly constrained one-dimensional code. We show
      that such structure affords computational advantages for face detection and
      decoding, including robustness to normal environmental image degradation, but
      makes faces vulnerable to certain classes of transformation that change the
      sequence of bars such as spatial inversion or contrast-polarity reversal.

PMID- 19757912
TI  - Stereo vision requires an explicit encoding of vertical disparity.
AB  - Vertical disparities influence the perception of 3D depth, but little is known
      about the neuronal mechanisms underlying this. One possibility is that these
      perceptual effects are mediated by an explicit encoding of two-dimensional
      disparity. Recently, J. C. A. Read and B. G. Cumming (2006) pointed out that
      current psychophysical and physiological evidence is consistent with a much more
      economical one-dimensional encoding. Almost all relevant information about
      vertical disparity could in theory be extracted from the activity of purely
      horizontal-disparity sensors. Read and Cumming demonstrated that such a 1D system
      would experience Ogle's induced effect, a famous illusion produced by vertical
      disparity. Here, we test whether the brain employs this 1D encoding, using a
      version of the induced effect stimulus that simulates the viewing geometry at
      infinity and thus removes the cues which are otherwise available to the 1D model.
      This condition was compared to the standard induced effect stimulus, presented on
      a frontoparallel screen at finite viewing distance. We show that the induced
      effects experienced under the two conditions are indistinguishable. This rules
      out the 1D model proposed by Read and Cumming and shows that vertical disparity,
      including sign, must be explicitly encoded across the visual field.

PMID- 19757913
TI  - When a never-seen but less-occluded image is better recognized: evidence from
      same-different matching experiments and a model.
AB  - Empirical studies of human object recognition have found that a query image
      different from that previously seen almost invariably gives rise to inferior
      recognition performance than a query image identical to that previously seen. In
      the present study of same-different matching, we demonstrate that a query image
      of a face or a Chinese character that was less occluded than that previously seen
      can yield more accurate positive identification than a query image identical to
      that previously seen. However, when occlusion of the second image was further
      reduced, or when the faces were inverted, this effect disappeared. These findings
      indicate that the representation of a partially occluded object is effectively
      less occluded, and that the ability of the visual system to overcome occlusion is
      limited and dependent on its familiarity with the perceived object. A model with
      limited capacity to overcome occlusion was proposed to qualitatively account for
      the results.

PMID- 19757914
TI  - An experimental criterion for consistency in interpolation of partly occluded
      contours.
AB  - We develop an experimental measure of consistency of interpolation of partly
      occluded contours based entirely on observers' interpolation performance. We
      first describe the measure, which is based on a two-probe task that compares an
      observer's interpolation settings at a particular location with vs. without the
      observer's own setting presented at a nearby location. We then report two
      experiments aimed at investigating the behavior of the measure. The first
      compares the proposed measure to the predictions of contour completion models.
      The second investigates its performance in the Poggendorff and related
      configurations. We find that consistency covaries with relatability and
      cocircularity (both interpreted in graded terms) and, sensibly, yields a low
      measure for interpolation in the Poggendorff configuration. We conclude that the
      proposed measure of consistency operationalizes an important aspect of what is
      meant by the "strength" of a partly occluded contour.

PMID- 19757915
TI  - ARTSCENE: A neural system for natural scene classification.
AB  - How do humans rapidly recognize a scene? How can neural models capture this
      biological competence to achieve state-of-the-art scene classification? The
      ARTSCENE neural system classifies natural scene photographs by using multiple
      spatial scales to efficiently accumulate evidence for gist and texture. ARTSCENE
      embodies a coarse-to-fine Texture Size Ranking Principle whereby spatial
      attention processes multiple scales of scenic information, from global gist to
      local textures, to learn and recognize scenic properties. The model can
      incrementally learn and rapidly predict scene identity by gist information alone,
      and then accumulate learned evidence from scenic textures to refine this
      hypothesis. The model shows how texture-fitting allocations of spatial attention,
      called attentional shrouds, can facilitate scene recognition, particularly when
      they include a border of adjacent textures. Using grid gist plus three shroud
      textures on a benchmark photograph dataset, ARTSCENE discriminates 4 landscape
      scene categories (coast, forest, mountain, and countryside) with up to 91.85%
      correct on a test set, outperforms alternative models in the literature which use
      biologically implausible computations, and outperforms component systems that use
      either gist or texture information alone.

PMID- 19757916
TI  - Neuronal convergence in early contrast vision: binocular summation is followed by
      response nonlinearity and area summation.
AB  - We assessed summation of contrast across eyes and area at detection threshold
      (C(t)). Stimuli were sine-wave gratings (2.5 c/deg) spatially modulated by cosine
      and anticosine-phase raised plaids (0.5 c/deg components oriented at +/-45
      degrees ). When presented dichoptically the signal regions were interdigitated
      across eyes but produced a smooth continuous grating following their linear
      binocular sum. The average summation ratio (C(t1)/([C(t1+2)]) for this stimulus
      pair was 1.64 (4.3 dB). This was only slightly less than the binocular summation
      found for the same patch type presented to both eyes, and the area summation
      found for the two different patch types presented to the same eye. We considered
      192 model architectures containing each of the following four elements in all
      possible orders: (i) linear summation or a MAX operator across eyes, (ii) linear
      summation or a MAX operator across area, (iii) linear or accelerating contrast
      transduction, and (iv) additive Gaussian, stochastic noise. Formal equivalences
      reduced this to 62 different models. The most successful four-element model was:
      linear summation across eyes followed by nonlinear contrast transduction, linear
      summation across area, and late noise. Model performance was enhanced when
      additional nonlinearities were placed before binocular summation and after area
      summation. The implications for models of probability summation and uncertainty
      are discussed.

PMID- 19757917
TI  - Contrast independence of dynamic random dot correlogram evoked VEP amplitude.
AB  - Dynamic random dot correlograms (DRDCs) are binocular stimuli that evoke a
      percept and a visual evoked potential (VEP) only in case of a mature and
      functional binocular system. DRDC-VEP is a method extensively used to study
      cortical binocularity in human infants and nonverbal children. Although the DRDC
      VEP was invented 3 decades ago, neither the fundamental parameters, including
      contrast, of the stimulation nor the cerebral processing mechanisms have been
      clarified. The objective of the present study was to investigate the variability
      and detectability of adults' VEPs to DRDC under different stimulus contrast
      conditions. DRDCs were presented on the red and green channels of a computer
      monitor and were viewed with red-green goggles. The steady state DRDC-VEPs were
      recorded in healthy adult volunteers, and response reliability was assessed by
      the T(circ)(2) statistic. DRDC-VEP amplitude was independent of contrast, while
      VEP phases showed a weak correlation with contrast. Contrast invariance of DRDC
      VEP amplitude suggests a very high contrast gain and dominant magnocellular input
      to the binocular correlation processing system.

PMID- 19757918
TI  - Deficits in local and global motion perception arising from abnormal eye
      movements.
AB  - Albino mammals exhibit a range of visual deficits including disrupted hemispheric
      pathways, an underdeveloped central retina, and nystagmus. Recently, it has been
      reported that albino animals also show deficits in the processing of visual
      motion, exhibiting higher motion coherence thresholds (MCTs; the proportion of
      coherently moving elements within a field of randomly moving distracters required
      to reliably report direction). Here we compare MCTs-collected from human
      observers with albinism-with an equivalent noise analysis of their fine-direction
      discrimination and report that their loss in motion sensitivity operates at both
      the level of local motion processing (of small objects) and at the later stage of
      global motion pooling. We also compare results from observers with aniridia
      (characterized by underdeveloped central retina and nystagmus but normal
      hemispheric visual pathways) and a rare group of observers with albinism who show
      no nystagmus. For the observers tested, nystagmus proved to be a common feature
      of individuals showing elevated MCTs. Since it is likely that motion perception
      is influenced by environmental factors early in development we postulate that the
      effect of congenital nystagmus on the temporal structure of the natural visual
      diet disrupts the ability of motion pathways to form normally.

PMID- 19757919
TI  - Using fMRI to distinguish components of the multiple object tracking task.
AB  - Multiple object tracking (MOT) has proven to be a powerful technique for studying
      sustained selective attention. However, surprisingly little is known about its
      underlying neural mechanisms. Previous fMRI investigations have identified
      several brain areas thought to be involved in MOT, but there were disagreements
      between the studies, none distinguished between the act of tracking targets and
      the act of attending targets, and none attempted to determine which of these
      brain areas interact with each other. Here we address these three issues. First,
      using more observers and a random effects analysis, we show that some of the
      previously identified areas may not play a specific role in MOT. Second, we show
      that the frontal eye fields (FEF), the anterior intraparietal sulcus (AIPS), the
      superior parietal lobule (SPL), the posterior intraparietal sulcus (PIPS) and the
      human motion area (MT+) are differentially activated by the act of tracking, as
      distinguished from the act of attention. Finally, by using an algorithm modified
      from the computer science literature, we were able to map the interactions
      between these brain areas.

PMID- 19757920
TI  - Modeling visual search on a rough surface.
AB  - The LNL (linear, non-linear, linear) model has previously been successfully
      applied to the problem of texture segmentation. In this study we investigate the
      extent to which a simple LNL model can simulate human performance in a search
      task involving a target on a textured surface. Two different classes of surface
      are considered: 1/f(beta)-noise and near-regular textures. We find that in both
      cases the search performance of the model does not differ significantly from that
      of people, over a wide range of task difficulties.

PMID- 19757921
TI  - Early-vision brain responses which predict human visual segmentation and
      learning.
AB  - Brain processes underlying visual segmentation have been widely studied, being
      part of the basic processes underlying perception. However, the underlying
      constraints on perceptual thresholds, set by neuronal processing, remain unclear.
      Here, the relationship between human visual performance and brain activity was
      examined using the backward-masked texture segmentation task. Performance showed
      dependence on the time-interval between target and mask as well as on the amount
      of prior practice. Correspondingly, early components of human event-related
      potentials (ERPs) recorded over occipital electrodes showed strong interactions
      between target and mask responses, suggesting interference with perception
      processes when the presented mask interacts with sustained target processing.
      These interactions, revealing an otherwise undetected extended processing time
      course beyond the early component of the target response, enabled us to quantify
      individual neuronal thresholds that closely matched the behavioral thresholds (r
      = 0.93, p = 0.00003). Furthermore, these neuronal thresholds could be improved by
      practice, suggesting neuronal mechanisms affected by perceptual learning.
      Predicting performance level not directly detected in the ERP but rather by
      further interactions shown here in early stages of the visual hierarchy may have
      important implications in the study of human perception. Practice seems to reduce
      the temporal interactions between the successive stimuli, revealing brain
      processes underlying perceptual learning.

PMID- 19757923
TI  - Crowding, reading, and developmental dyslexia.
AB  - We tested the hypothesis that crowding effects are responsible for the reading
      slowness characteristic of developmental dyslexia. A total of twenty-nine Italian
      dyslexics and thirty-three age-matched controls participated in various parts of
      the study. In Experiment 1, we measured contrast thresholds for identifying
      letters and words as a function of stimulus duration. Thresholds were higher in
      dyslexics than controls for words (at a limited time exposure) but not for single
      letters. Adding noise to the stimuli produced comparable effects in dyslexics and
      controls. At the long time exposure thresholds were comparable in the two groups.
      In Experiment 2, we measured the spacing between a target letter and two flankers
      at a fixed level of performance as a function of eccentricity and size. With
      eccentricity, the critical spacing (CS) scaled in the control group with 0.62
      proportionality (a value of b close to Bouma's law, 0.50) and with a greater
      proportionality (0.95) in the dyslexic group. CS was independent of size in both
      groups. In Experiment 3, we examined the critical print size (CPS), that is, the
      increase in reading rate up to a critical character size (S. T. Chung, J. S.
      Mansfield, & G. E. Legge, 1998). CPS of dyslexic children was greater than that
      of controls. Individual maximal reading speed was predicted by individual bs
      (from Experiment 2). The maximal reading rate achieved by dyslexics at CPS (and
      also for larger print sizes) was below the values observed in controls. We
      conclude that word analysis in dyslexics is slowed because of greater crowding
      effects, which limit letter identification in multi-letter arrays across the
      visual field. We propose that the peripheral reading of normal readers might
      constitute a model for dyslexic reading. The periphery model accounts for 60% of
      dyslexics' slowness. After compensating for crowding, the dyslexics' reading rate
      remains slower than that of proficient readers. This failure is discussed in
      terms of a developmental learning effect.

PMID- 19757922
TI  - Perceptual consequences of visual performance fields: the case of the line motion
      illusion.
AB  - Illusory line motion (ILM) is the illusion that a line, preceded by a small dot
      (cue) near one end, is perceived to shoot out from the dot even though the line
      is physically presented at once. Does this illusion result from a low-level
      motion effect, a gradient of exogenous spatial attention, or both? Given that
      exogenous attention speeds visual processing unequally at isoeccentric cardinal
      locations (M. Carrasco, A. M. Giordano, & B. McElree, 2004), we hypothesized that
      the contribution of attention to ILM would follow the same pattern. We
      characterized psychometric functions of perceived line motion direction, for 1.5
      degrees stimuli with varying amounts of physical line motion (8 levels) at four
      cardinal locations. We used three cue conditions to separate the effects of
      attention from low-level motion-a single cue to draw focal attention to the
      stimulus location, a distributed cue with elements near all four possible
      stimulus locations, and no visual cue. Distributed and single cues generate
      identical effects along the horizontal meridian, but the effect of the single cue
      is progressively greater along the vertical meridian, more so at the top location
      ("North"). We conclude that the low-level motion explanation accounts for the
      majority of the canonical example of the ILM (line preceded by a single dot)
      effect used in our study.

PMID- 19757924
TI  - Interaction of spatial and temporal factors in psychophysical estimates of
      surround suppression.
AB  - Recent psychophysical work has shown that performance on a direction
      discrimination task decreases with increasing stimulus size, provided the
      stimulus is high in contrast. This psychophysical surround suppression has been
      linked to the inhibitory spatial surrounds that have been observed throughout the
      primate visual system. In this work we have examined a temporal factor that may
      also contribute to psychophysical surround suppression. Consistent with previous
      work, we found that psychophysical surround suppression is strongest when a high
      contrast motion stimulus is presented very briefly so that the appearance of the
      stimulus coincided with its motion. However, when a brief delay was inserted
      between the stimulus onset and the onset of motion, the counterintuitive effects
      of stimulus size disappeared. The effect of the motion onset asynchrony (MOA) was
      strongest when the stationary stimulus immediately preceded the stimulus motion
      and when stimulus orientation during the MOA was very similar to that during the
      motion presentation. We conclude that psychophysical surround suppression is
      partially linked to the temporal structure of the stimulus, more precisely to a
      masking effect caused by sudden stimulus onsets (and to a smaller degree stimulus
      offsets).

PMID- 19757925
TI  - Color constancy improves for real 3D objects.
AB  - In this study human color constancy was tested for two-dimensional (2D) and three
      dimensional (3D) setups with real objects and lights. Four different illuminant
      changes, a natural selection task and a wide choice of target colors were used.
      We found that color constancy was better when the target color was learned as a
      3D object in a cue-rich 3D scene than in a 2D setup. This improvement was
      independent of the target color and the illuminant change. We were not able to
      find any evidence that frequently experienced illuminant changes are better
      compensated for than unusual ones. Normalizing individual color constancy hit
      rates by the corresponding color memory hit rates yields a color constancy index,
      which is indicative of observers' true ability to compensate for illuminant
      changes.

PMID- 19757926
TI  - 'Zigzag motion' goes in unexpected directions.
AB  - In a novel 'zigzag motion' display, random dots made alternate long and short
      jumps, 10 mm downward and 1 mm to the right. The zigs and zags were either at
      right angles (differing by 90 degrees) or in opposite directions (180 degrees).
      RESULT: The perceived direction of motion varied with the viewing distance or
      spatial scale. During close-up [or distant] viewing the display appeared to move
      in the direction of the short [or long] jumps. When the motion was stopped after
      30 s, a motion aftereffect (MAE) was seen, driven by the short jumps but not the
      long jumps. Therefore, the perceived direction of motion was dissociated from its
      aftereffect. A picture rotated alternately 5 degrees clockwise (CW) and 1 degrees
      counterclockwise (CCW) and appeared to rotate jerkily CW. When stopped, a
      clockwise MAE was seen, appropriate to the small 1 degrees jumps. If the test
      field contained blurred, dynamic visual noise, the MAE was now CCW, appropriate
      to the large 5 degrees jumps; the large jumps drove the perceived motion
      direction and dynamic MAE, but the small jumps drove the static MAE. CONCLUSION:
      Winner-take-all competition between pathways tuned to fast and slow movements.
      Their independent adaptation gave opposite static and dynamic MAEs.

PMID- 19757927
TI  - Optimum spatiotemporal receptive fields for vision in dim light.
AB  - Many nocturnal insects depend on vision for daily life and have evolved different
      strategies to improve their visual capabilities in dim light. Neural summation of
      visual signals is one strategy to improve visual performance, and this is likely
      to be especially important for insects with apposition compound eyes. Here we
      develop a model to determine the optimum spatiotemporal sampling of natural
      scenes at gradually decreasing light levels. Image anisotropy has a strong
      influence on the receptive field properties predicted to be optimal at low light
      intensities. Spatial summation between visual channels is predicted to extend
      more strongly in the direction with higher correlations between the input
      signals. Increased spatiotemporal summation increases signal-to-noise ratio at
      low frequencies but sacrifices signal-to-noise ratio at higher frequencies. These
      results, while obtained from a model of the insect visual system, are likely to
      apply to visual systems in general.

PMID- 19757929
TI  - Contrast-reversal abolishes perceptual learning.
AB  - We tested the effects of contrast reversal on perceptual learning in a 10AFC
      texture identification task. Four groups of subjects performed the task on two
      consecutive days. One group saw the same textures on both days, whereas three
      other groups saw novel, rotated (180 deg), or contrast-reversed textures on the
      second day. Response accuracy improved during the first day in all groups.
      Accuracy decreased significantly at the start of Day 2 in the groups who saw
      novel, rotated or contrast-reversed textures, but not in the group who saw the
      same textures. Moreover, the drop in performance was the same in the groups who
      saw novel, rotated, and contrast-reversed textures. Control experiments showed
      that making subjects aware of the stimulus transformations at the start of either
      the first or second day did not alter the results. Hence, the effects of contrast
      reversal and 180 deg rotation on the generalization of learning were the same as
      the effect of using novel stimuli, and knowledge of the stimulus transformation
      did not reduce their effects. We consider the implications of this pattern of
      results for the neural mechanisms recruited during the identification and
      learning of two-dimensional visual patterns.

PMID- 19757928
TI  - Perceptual organization in the tilt illusion.
AB  - The tilt illusion is a paradigmatic example of contextual influences on
      perception. We analyze it in terms of a neural population model for the
      perceptual organization of visual orientation. In turn, this is based on a well
      found treatment of natural scene statistics, known as the Gaussian Scale Mixture
      model. This model is closely related to divisive gain control in neural
      processing and has been extensively applied in the image processing and
      statistical learning communities; however, its implications for contextual
      effects in biological vision have not been studied. In our model, oriented neural
      units associated with surround tilt stimuli participate in divisively normalizing
      the activities of the units representing a center stimulus, thereby changing
      their tuning curves. We show that through standard population decoding, these
      changes lead to the forms of repulsion and attraction observed in the tilt
      illusion. The issues in our model readily generalize to other visual attributes
      and contextual phenomena, and should lead to more rigorous treatments of
      contextual effects based on natural scene statistics.

PMID- 19757930
TI  - Learning in shifts of transient attention improves recognition of parts of
      ambiguous figure-ground displays.
AB  - Previously demonstrated learning effects in shifts of transient attention have
      only been shown to result in beneficial effects upon secondary discrimination
      tasks and affect landing points of express saccades. Can such learning result in
      more direct effects upon perception than previously demonstrated? Observers
      performed a cued Vernier acuity discrimination task where the cue was one of a
      set of ambiguous figure-ground displays (with a black and white part). The
      critical measure was whether, if a target appeared consistently within a part of
      a cue of a certain brightness, this would result in learning effects and whether
      such learning would then affect recognition of the cue parts. Critically the
      target always appeared within the same part of each individual cue. Some cues
      were used in early parts of streaks of repetition of cue-part brightness, and
      others in latter parts of such streaks. All the observers showed learning in
      shifts of transient attention, with improved performance the more often the
      target appeared within the part of the cue of the same brightness. Subsequently
      the observers judged whether cue-parts had been parts of the cues used on the
      preceding discrimination task. Recognition of the figure parts, where the target
      had consistently appeared, improved strongly with increased length of streaks of
      repetition of cue-part brightness. Learning in shifts of transient attention
      leads not only to faster attention shifts but to direct effects upon perception,
      in this case recognition of parts of figure-ground ambiguous cues.

PMID- 19757931
TI  - Adaptive precision pooling of model neuron activities predicts the efficiency of
      human visual learning.
AB  - When performing a perceptual task, precision pooling occurs when an organism's
      decisions are based on the activities of a small set of highly informative
      neurons. The Adaptive Precision Pooling Hypothesis links perceptual learning and
      decision making by stating that improvements in performance occur when an
      organism starts to base its decisions on the responses of neurons that are more
      informative for a task than the responses that the organism had previously used.
      We trained human subjects on a visual slant discrimination task and found their
      performances to be suboptimal relative to an ideal probabilistic observer. Why
      were subjects suboptimal learners? Our computer simulation results suggest a
      possible explanation, namely that there are few neurons providing highly reliable
      information for the perceptual task, and that learning involves searching for
      these rare, informative neurons during the course of training. This explanation
      can account for several characteristics of human visual learning, including the
      fact that people often show large differences in their learning performances with
      some individuals showing no performance improvements, other individuals showing
      gradual improvements during the course of training, and still others showing
      abrupt improvements. The approach described here potentially provides a unifying
      framework for several theories of perceptual learning including theories stating
      that learning is due to adaptations of the weightings of read-out connections
      from early visual representations, external noise filtering or internal noise
      reduction, increases in the efficiency with which learners encode task-relevant
      information, and attentional selection of specific neural populations which
      should undergo adaptation.

PMID- 19757932
TI  - Spatial localization: interpolating first- and second-order visual structure.
AB  - Human observers are able to localize the relative position of objects defined by
      Gaussian variations in either luminance (1st order) or contrast (2nd order).
      However, positional sensitivity is significantly poorer for 2nd- than for 1st
      order stimuli. These judgments require the visual system to construct a
      representation of pertinent variation from a number of individual retinal samples
      a process known as interpolation. We compared 1st- and 2nd-order interpolation
      mechanisms to examine whether differences in this process underlie differences in
      positional sensitivity. Observers were required to judge the relative position of
      two vertically separated 1st- or 2nd-order Gaussian distributions. The
      distributions were discretely sampled, and both sample number and separation were
      systematically varied. Results showed that with fixed sample separation (1.9 or
      7.7 arcmin), optimum localization was obtained with a minimum of 4-6 samples, for
      both 1st- and 2nd-order stimuli. When sample number is maintained above this
      critical value, marked changes in sample separation (0 to 9 arcmin) had
      relatively little impact on thresholds for both 1st-order and 2nd-order stimuli.
      These results suggest that both 1st-order and 2nd-order interpolation mechanisms
      are limited by sample number rather than separation, and require a similar number
      of samples to mediate positional judgments.

PMID- 19757933
TI  - A crowding model of visual clutter.
AB  - Visual information is difficult to search and interpret when the density of the
      displayed information is high or the layout is chaotic. Visual information that
      exhibits such properties is generally referred to as being "cluttered." Clutter
      should be avoided in information visualizations and interface design in general
      because it can severely degrade task performance. Although previous studies have
      identified computable correlates of clutter (such as local feature variance and
      edge density), understanding of why humans perceive some scenes as being more
      cluttered than others remains limited. Here, we explore an account of clutter
      that is inspired by findings from visual perception studies. Specifically, we
      test the hypothesis that the so-called "crowding" phenomenon is an important
      constituent of clutter. We constructed an algorithm to predict visual clutter in
      arbitrary images by estimating the perceptual impairment due to crowding. After
      verifying that this model can reproduce crowding data we tested whether it can
      also predict clutter. We found that its predictions correlate well with both
      subjective clutter assessments and search performance in cluttered scenes. These
      results suggest that crowding and clutter may indeed be closely related concepts
      and suggest avenues for further research.

PMID- 19757934
TI  - Meaningful auditory information enhances perception of visual biological motion.
AB  - Robust perception requires efficient integration of information from our various
      senses. Much recent electrophysiology points to neural areas responsive to
      multisensory stimulation, particularly audiovisual stimulation. However,
      psychophysical evidence for functional integration of audiovisual motion has been
      ambiguous. In this study we measure perception of an audiovisual form of
      biological motion, tap dancing. The results show that the audio tap information
      interacts with visual motion information, but only when in synchrony,
      demonstrating a functional combination of audiovisual information in a natural
      task. The advantage of multimodal combination was better than the optimal maximum
      likelihood prediction.

PMID- 19757935
TI  - Color perception in the intermediate periphery of the visual field.
AB  - Color perception changes across the visual field. It is best in the fovea and
      declines in the periphery. Sensitivity to red-green color variations declines
      more steeply toward the periphery than sensitivity to luminance or blue-yellow
      colors. It is thought that this decline is due to the increasing size of
      receptive fields of parvocellular retinal ganglion cells and the unselective or
      random contribution of L- and M-cones to the receptive field surround. In earlier
      psychophysical studies it has been found that L - M cone opponency becomes absent
      above 30 deg. However, physiological experiments in macaque monkeys have shown
      that midget ganglion cells exist in the intermediate zone of the peripheral
      retina (20-50 deg) that are strongly cone opponent. Here we explore this
      contradiction between physiological and psychophysical research, using stimuli of
      variable size at eccentricities of up to 50 deg. We found that chromatic
      detection gets worse with increasing eccentricity but is still possible even at
      large eccentricities. Our results show that chromatic detection at these
      eccentricities is mediated by cone-opponent mechanisms.

PMID- 19757936
TI  - Quantifying the effect of natural and arbitrary sensorimotor contingencies on
      chromatic judgments.
AB  - When a body movement systematically co-occurs with a stimulus, a change in
      perception to compensate for this correlation may occur. In Experiment 1 (similar
      to A. Bompas & J. K. O'Regan, 2006), we induced a correlation between leftward
      eye saccades and a red stimulus, and rightward eye saccades and a green stimulus.
      In a subsequent test phase, observers compared the color of two stimuli after
      leftward and rightward saccades. The major result was that stimuli tended to look
      greener after a leftward saccade and redder after a rightward saccade (A. Bompas
      & J. K. O'Regan, 2006). Measured here in meaningful units for the first time, the
      shift in the point of subjective equality was approximately d' = 0.4, a
      remarkably large effect for only 40 minutes of eye movement/color exposure. A
      control experiment ruled out a simple reduction in initial bias as the cause of
      the effect. In Experiment 2, we hypothesized that the blue of the sky might cause
      an initial bias to judge spots seen with upward gaze as "yellower"; this
      expectation was not met, but the basic effect was replicated and extended to
      other chromaticities and eye movement directions. Experiment 3 substituted
      listening to tones for the eye movements (a sensorisensory correlation) to
      explore differences between sensorimotor adaptation and sensory integration;
      neither effect was found for our task. Sensorimotor adaptation can be a
      remarkably powerful influence on perception; because it operates in a
      compensatory direction, it may oppose the effects of sensory integration,
      depending upon task demands.

PMID- 19757937
TI  - Transsaccadic identification of highly similar artificial shapes.
AB  - Multiple times per second, the visual system succeeds in making a seamless
      transition between presaccadic and postsaccadic perception. The nature of the
      transsaccadic representation needed to support this was commonly thought to be
      sparse and abstract. However, recent studies have suggested that detailed visual
      information is transferred across saccades as well. Here, we seek to confirm that
      preview effects of visual detail on postsaccadic perception do indeed occur. We
      presented subjects with highly similar artificial shapes, preceded by a
      congruent, an incongruent, or no preview. Postsaccadic recognition performance
      was measured, while the contrast of presaccadic and postsaccadic stimuli was
      manipulated independently. The results show that congruent previews provided a
      benefit to the recognition performance of postsaccadic stimuli, compared to no
      preview conditions. Incongruent previews induced a recognition accuracy cost,
      combined with a recognition speed benefit. A second experiment showed that these
      effects can disappear when stimulus presentation is interrupted with a
      postsaccadic visual mask. We conclude that visual detail contained in
      transsaccadic memory can affect the postsaccadic percept. Furthermore, we find
      that the transsaccadic representation supporting this process is contrast
      independent, but that postsaccadic contrast, through its effect on the
      reliability of information, can affect the degree to which it is employed.

PMID- 19757938
TI  - Brain responses strongly correlate with Weibull image statistics when processing
      natural images.
AB  - The visual appearance of natural scenes is governed by a surprisingly simple
      hidden structure. The distributions of contrast values in natural images
      generally follow a Weibull distribution, with beta and gamma as free parameters.
      Beta and gamma seem to structure the space of natural images in an ecologically
      meaningful way, in particular with respect to the fragmentation and texture
      similarity within an image. Since it is often assumed that the brain exploits
      structural regularities in natural image statistics to efficiently encode and
      analyze visual input, we here ask ourselves whether the brain approximates the
      beta and gamma values underlying the contrast distributions of natural images. We
      present a model that shows that beta and gamma can be easily estimated from the
      outputs of X-cells and Y-cells. In addition, we covaried the EEG responses of
      subjects viewing natural images with the beta and gamma values of those images.
      We show that beta and gamma explain up to 71% of the variance of the early ERP
      signal, substantially outperforming other tested contrast measurements. This
      suggests that the brain is strongly tuned to the image's beta and gamma values,
      potentially providing the visual system with an efficient way to rapidly classify
      incoming images on the basis of omnipresent low-level natural image statistics.

PMID- 19757939
TI  - Two contrast adaptation processes: contrast normalization and shifting,
      rectifying contrast comparison.
AB  - We present psychophysical results demonstrating the interaction of two contrast
      adaptation processes in human vision: (1) A contrast-gain-control process of the
      normalization type and (2) a recently-discovered shifting, rectifying contrast
      comparison process. Observers adapted (for 1 s) to a grid of Gabor patches at one
      contrast, then a brief (94 ms) test pattern was shown, and then the adapt pattern
      was shown again (1 s). The test pattern was the same as the adapt pattern except
      that the Gabor patches had two different contrasts arranged to create vertical or
      horizontal contrast-defined stripes. Observers identified the orientation of the
      test pattern's stripes. Performance is a complicated ("butterfly shaped")
      function of the average test contrast, centered at the adapt contrast. This shape
      is a consequence of the interaction of the two contrast adaptation processes. At
      the ends of the function are "Weber zones" in which the contrast-gain-control
      process dominates, and at the center of the function is a "Buffy zone" in which
      the recently-discovered contrast-comparison process dominates.

PMID- 19757940
TI  - Task precision at transfer determines specificity of perceptual learning.
AB  - Perceptual learning, the improvement in performance with practice, reflects
      plasticity in the adult visual system. We challenge a standard claim that
      specificity of perceptual learning depends on task difficulty during training,
      instead showing that specificity, or conversely transfer, is primarily controlled
      by the precision demands (i.e., orientation difference) of the transfer task.
      Thus, for an orientation discrimination task, transfer of performance improvement
      is observed in low-precision transfer tasks, while specificity of performance
      improvement is observed in high-precision transfer tasks, regardless of the
      precision of initial training. The nature of specificity places important
      constraints on mechanisms of transfer in visual learning. These results
      contribute to understanding generalization of practiced improvements that may be
      key to the development of expertise and for applications in remediation.

PMID- 19757941
TI  - Within-hemifield perceptual averaging of facial expressions predicted by neural
      averaging.
AB  - High-level visual neurons in the ventral stream typically have large receptive
      fields, supporting position-invariant object recognition but entailing poor
      spatial resolution. Consequently, when multiple objects fall within their large
      receptive fields, unless selective attention is deployed, their responses are
      averages of responses to the individual objects. We investigated a behavioral
      consequence of this neural averaging in the perception of facial expressions. Two
      faces (7 degrees -apart) were briefly presented (100-ms, backward-masked) either
      within the same visual hemifield (within-hemifield condition) or in different
      hemifields (between-hemifield condition). Face pairs included happy, angry, and
      valence-neutral faces, and observers rated the emotional valence of a post-cued
      face. Perceptual averaging of facial expressions was predicted only for the
      within-hemifield condition because the receptive fields of 'face-tuned' neurons
      are primarily confined within the contralateral field; the between-hemifield
      condition served to control for post-perceptual effects. Consistent with
      averaging, valence-neutral faces appeared more positive when paired with a happy
      face than when paired with an angry face, and affective intensities of happy and
      angry faces were reduced by accompanying valence-neutral or opposite-valence
      faces, in the within-hemifield relative to the between-hemifield condition. We
      thus demonstrated within-hemifield perceptual averaging of a complex feature as
      predicted by neural averaging in the ventral visual stream.

PMID- 19757942
TI  - Intermittent ambiguous stimuli: implicit memory causes periodic perceptual
      alternations.
AB  - When viewing a stimulus that has multiple plausible real-world interpretations,
      perception alternates between these interpretations every few seconds.
      Alternations can be halted by intermittently removing the stimulus from view. The
      same interpretation dominates over many successive presentations, and perception
      stabilizes. Here we study perception during long sessions of such intermittent
      presentation. We demonstrate that, rather than causing truly stable perception,
      intermittent presentation gives rise to a perceptual alternation cycle with its
      own characteristics and dependencies, different from those during continuous
      presentation. Alternations during intermittent viewing typically occur once every
      few minutes--much less frequently than the seconds-scale alternations during
      continuous viewing. Strikingly, alternations during intermittent viewing occur at
      fairly regular intervals, making for a surprisingly periodic alternation cycle.
      The duration of this cycle becomes longer as the blank duration between
      presentations is increased, reaching dozens of minutes in some cases. We
      interpret our findings in terms of a mathematical model that describes a neural
      network with competition between alternative interpretations. Network
      sensitivities depend on prior dominance, thus providing a memory for past
      perception. Slow changes in sensitivity produce both perceptual stabilization and
      the regular but infrequent alternations, meaning that the same memory traces are
      responsible for both. This model provides a good description of psychophysical
      findings, and offers several indications regarding their neural basis.

PMID- 19757943
TI  - Adaptive pooling of visual motion signals by the human visual system revealed
      with a novel multi-element stimulus.
AB  - The two-dimensional (2D) trajectory of visual motion is usually not directly
      available to the visual system. Local one-dimensional (1D) sensors initiate
      processing but can only restrict the solution to a set of speed and direction
      combinations consistent with the 2D trajectory. These 1D signals are then
      integrated across orientation and space to compute 2D signals. Both motion
      integrations are thought to occur in higher cortical areas, but it remains
      unclear whether 1D signals are integrated over orientation and space
      simultaneously (1D pooling process), or instead are integrated locally with the
      resulting 2D signals then spatially integrated (2D pooling process). From
      psychophysical responses to novel global-motion stimuli comprised of numerous
      Gabor (1D) or Plaid (2D) elements, here we show that the human visual system
      adaptively switches between 1D pooling and 2D pooling depending on the input.
      When local 2D signals cannot be determined, the visual system shows effective 1D
      pooling that approximately follows the intersection of constraints rule. On the
      other hand, when local 2D signals are available, the visual system shows 2D
      pooling that approximately follows the vector average rule. Spatial motion
      integration therefore exhibits great flexibility when estimating complex optic
      flows in natural scenes.

PMID- 19757944
TI  - Saliency, attention, and visual search: an information theoretic approach.
AB  - A proposal for saliency computation within the visual cortex is put forth based
      on the premise that localized saliency computation serves to maximize information
      sampled from one's environment. The model is built entirely on computational
      constraints but nevertheless results in an architecture with cells and
      connectivity reminiscent of that appearing in the visual cortex. It is
      demonstrated that a variety of visual search behaviors appear as emergent
      properties of the model and therefore basic principles of coding and information
      transmission. Experimental results demonstrate greater efficacy in predicting
      fixation patterns across two different data sets as compared with competing
      models.

PMID- 19757945
TI  - Viewing task influences eye movement control during active scene perception.
AB  - Expanding on the seminal work of G. Buswell (1935) and I. A. Yarbus (1967), we
      investigated how task instruction influences specific parameters of eye movement
      control. In the present study, 20 participants viewed color photographs of
      natural scenes under two instruction sets: visual search and memorization.
      Results showed that task influenced a number of eye movement measures including
      the number of fixations and gaze duration on specific objects. Additional
      analyses revealed that the areas fixated were qualitatively different between the
      two tasks. However, other measures such as average saccade amplitude and
      individual fixation durations remained constant across the viewing of the scene
      and across tasks. The present study demonstrates that viewing task biases the
      selection of scene regions and aggregate measures of fixation time on those
      regions but does not influence other measures, such as the duration of individual
      fixations.

PMID- 19757946
TI  - Stable individual differences in search strategy? The effect of task demands and
      motivational factors on scanning strategy in visual search.
AB  - Previous studies have demonstrated large individual differences in scanning
      strategy during a dynamic visual search task (E. Becic, A. F. Kramer, & W. R.
      Boot, 2007; W. R. Boot, A. F. Kramer, E. Becic, D. A. Wiegmann, & T. Kubose,
      2006). These differences accounted for substantial variance in performance.
      Participants who chose to search covertly (without eye movements) excelled,
      participants who searched overtly (with eye movements) performed poorly. The aim
      of the current study was to investigate the stability of scanning strategies
      across different visual search tasks in an attempt to explain why a large
      percentage of observers might engage in maladaptive strategies. Scanning strategy
      was assessed for a group of observers across a variety of search tasks without
      feedback (efficient search, inefficient search, change detection, dynamic
      search). While scanning strategy was partly determined by task demands, stable
      individual differences emerged. Participants who searched either overtly or
      covertly tended to adopt the same strategy regardless of the demands of the
      search task, even in tasks in which such a strategy was maladaptive. However,
      when participants were given explicit feedback about their performance during
      search and performance incentives, strategies across tasks diverged. Thus it
      appears that observers by default will favor a particular search strategy but can
      modify this strategy when it is clearly maladaptive to the task.

PMID- 19757947
TI  - Shape distortions and Gestalt grouping in anorthoscopic perception.
AB  - When a figure moves behind a stationary narrow slit, observers often report
      seeing the figure as a whole, a phenomenon called slit viewing or anorthoscopic
      perception. Interestingly, in slit viewing, the figure is perceived compressed
      along the axis of motion. As with other perceptual distortions, it is unclear
      whether the perceptual space in the vicinity of the slit or the representation of
      the figure itself undergoes compression. In a psychophysical experiment, we
      tested these two hypotheses. We found that the percept of a stationary bar,
      presented within the slit, was not distorted even when at the same time a circle
      underwent compression by moving through the slit. This result suggests that the
      compression of form results from figural rather than from space compression. In
      support of this hypothesis, we found that when the bar was perceptually grouped
      with the circle, the bar appeared compressed. Our results show that, in slit
      viewing, the distortion occurs at a non-retinotopic level where grouped objects
      are jointly represented.

PMID- 19757948
TI  - The contribution of human cone photoreceptors to the photopic flicker
      electroretinogram.
AB  - We aimed to noninvasively estimate the relative contribution of the cone
      photoreceptors to the photopic flicker electroretinogram (ERG) in humans.
      Responses to ganzfeld square-wave flicker (15, 30, and 60 Hz) were recorded in
      the presence of a rod-saturating background. We used a modified paired flash
      technique in which a bright probe flash was presented at different times during a
      flicker cycle and the ERG response was recorded. The cone photoreceptor response
      was estimated by comparing the relative amplitude of the response during a
      flicker cycle to the response in the absence of flicker, at early times after the
      presentation of the probe flash. The normalized responses were then scaled to
      absolute values based on the assumption that the response to 15-Hz flicker is
      dominated by the photoreceptor response at early times in a cycle (<15 ms). The
      postreceptoral contribution was obtained by subtracting the absolute
      photoreceptor response from the flicker response. The derived cone response
      showed a peak around 25 ms, from the start of the flicker cycle for 15-Hz and 30
      Hz flicker with no clear peak for 60-Hz flicker. In humans, the postreceptoral
      components dominate the photopic flicker ERG at 15, 30, and 60 Hz. The findings
      are comparable to those from pharmacological studies in monkeys.

PMID- 19757949
TI  - The S-cone contribution to luminance depends on the M- and L-cone adaptation
      levels: silent surrounds?
AB  - Under dim background conditions, the S-cones make little or no contribution to
      luminance (A. Eisner & D. I. MacLeod, 1980; W. Verdon & A. J. Adams, 1987), yet
      under conditions of intense long-wavelength adaptation, a small but robust
      contribution to luminance--as defined by heterochromatic flicker photometry (A.
      Stockman, D. I. MacLeod, & D. D. DePriest, 1987, 1991) or motion (J. Lee & C. F.
      Stromeyer, 1989)--can be found. Here, by using selective adaptation and/or
      tritanopic metamers to isolate the S-cone response, we investigate the dependence
      of the S-cone luminance input on changes in background wavelength and radiance.
      Interestingly, the S-cone luminance input disappears completely when no adapting
      background is present, even though the same S-cone stimulus makes a clear
      contribution to luminance when a background is present. The dependence of the S
      cone luminance input on the wavelength and radiance of the adapting background is
      surprising. We find that the S-cone signal can be measured on fields of 491 nm
      and longer wavelengths that exceed a criterion background radiance. These
      criterion radiances roughly follow an L + M spectral sensitivity, which suggests
      that the S-cone luminance input is silent unless the L- and M-cones are excited
      above a certain level. We hypothesize that the L + M cone signals produced by the
      steady adapting backgrounds somehow "gate" the S-cone luminance signals, perhaps
      by being modulated by them.

PMID- 19757950
TI  - Visual scanning in the recognition of facial affect: is there an observer sex
      difference?
AB  - This investigation assessed whether differences exist in the way males and
      females overtly orient their visual attention to salient facial features while
      viewing static emotional facial expressions. Eye movements were recorded while
      fifty healthy participants (23 males, 27 females) viewed a series of six
      universal facial expressions. Groups were compared with respect to accuracy and
      reaction time in emotional labeling. The number and duration of foveal fixations
      to four predefined facial areas of interest (AOIs)--each eye, nose, mouth--were
      also recorded. There were no significant group differences with respect to
      accuracy (p = 0.997), though females were significantly faster than males in
      correctly identifying expressions (p = 0.047). Analysis of the visual scan path
      revealed that while both groups spent more time and looked more frequently at the
      eye region, males spent significantly more time viewing the nose and mouth. The
      duration and number of fixations made to the nose were significantly greater in
      males (p < 0.05). This study is the first to show reaction time differences
      between the sexes across a range of universal emotions. Further, this is the
      first work to suggest the orienting of attention to the lower part of the face,
      especially the nose, appears to differentiate the sexes.

PMID- 19757951
TI  - Induced temporal variation at frequencies not in the stimulus: evidence for a
      neural nonlinearity.
AB  - The perceived color of a light depends on surrounding light. When the surround
      varies slowly over time, a central, physically steady light is perceived to vary
      also. This perceived temporal variation of the central region, however, is
      strongly attenuated when the surround varies faster than approximately 3 Hz (R.
      L. De Valois, M. A. Webster, K. K. De Valois, & B. Lingelbach, 1986). The
      classical explanation is low-pass temporal filtering at a cortical stage that
      attenuates the neural representation of temporal frequencies capable of causing
      induced temporal variation. This theory assumes neural responses are linear, so
      only temporal frequencies in the stimulus are represented in the neural response.
      The current experiments revealed that temporal frequencies above 3 Hz are capable
      of inducing temporal variation. Specifically, with two temporal frequencies
      superimposed in the surround, the induced temporal variation in the uniform
      region is at the difference frequency of these two frequencies, even though this
      frequency is not physically present in the stimulus. The results are accounted
      for by a nonlinear neural process, which causes temporal variation at the
      difference frequency, and a following linear temporal filter.

PMID- 19757953
TI  - Influence of accommodation on off-axis refractive errors in myopic eyes.
AB  - INTRODUCTION: This study aims to understand off-axis refraction during
      accommodation and to identify whether the relative hyperopia generally observed
      in myopic eyes changes with accommodation. METHOD: Twenty bilateral myopes (18 to
      33 years) between -0.50 D and -4.25 D (spherical equivalent) and astigmatism less
      than 1.25 D participated in this study. A soft contact lens was used to correct
      refractive error for all measurements. Non-cycloplegic autorefraction was
      measured at the fovea and 20 degrees, 30 degrees, and 40 degrees eccentricities
      in the nasal and temporal retina at distances of 2 m, 40 cm, and 30 cm. RESULTS:
      Peripheral refractive error, relative to central refraction, became less
      hyperopic with increasing eccentricity and with increasing accommodation. Lag of
      accommodation increased with accommodation (p < 0.001) shifting the image-shell
      backward relative to the retina. In the farther periphery, there was either no
      change in refractive error or increased myopic shifts with accommodation.
      Astigmatism increased with eccentricity and significantly increased in the
      farther eccentricities with accommodation (p < 0.001). CONCLUSION: Myopes display
      hyperopic shifts in the center and near peripheral field during near-viewing,
      while the farther periphery either remains unshifted or demonstrates a myopic
      shift. These results are due to the combined effect of lag of accommodation and
      an increased curvature of field during accommodation.

PMID- 19757952
TI  - Inter-ocular contrast normalization in human visual cortex.
AB  - The brain combines visual information from the two eyes and forms a coherent
      percept, even when inputs to the eyes are different. However, it is not clear how
      inputs from the two eyes are combined in visual cortex. We measured fMRI
      responses to single gratings presented monocularly, or pairs of gratings
      presented monocularly or dichoptically with several combinations of contrasts.
      Gratings had either the same orientation or orthogonal orientations (i.e.,
      plaids). Observers performed a demanding task at fixation to minimize top-down
      modulation of the stimulus-evoked responses. Dichoptic presentation of compatible
      gratings (same orientation) evoked greater activity than monocular presentation
      of a single grating only when contrast was low (<10%). A model that assumes
      linear summation of activity from each eye failed to explain binocular responses
      at 10% contrast or higher. However, a model with binocular contrast
      normalization, such that activity from each eye reduced the gain for the other
      eye, fitted the results very well. Dichoptic presentation of orthogonal gratings
      evoked greater activity than monocular presentation of a single grating for all
      contrasts. However, activity evoked by dichoptic plaids was equal to that evoked
      by monocular plaids. Introducing an onset asynchrony (stimulating one eye 500 ms
      before the other, which under attentive vision results in flash suppression) had
      no impact on the results; the responses to dichoptic and monocular plaids were
      again equal. We conclude that when attention is diverted, inter-ocular
      suppression in V1 can be explained by a normalization model in which the mutual
      suppression between orthogonal orientations does not depend on the eye of origin,
      nor on the onset times, and cross-orientation suppression is weaker than inter
      ocular (same orientation) suppression.

PMID- 19757954
TI  - Uncertainty reveals surround modulation of shape.
AB  - Noisy estimations of shape can be partially resolved by incorporating relevant
      information from the context. The effect of surround stimuli on shape perception
      becomes clear in illusions of shape contrast and assimilation. In this study, we
      answer the question how a surround-induced bias depends on the reliability of
      shape signals. This way, we assess the processes by which an observer
      incorporates relevant data from the context into the shape estimate. We
      selectively added visual noise to the center and surround and compared a bias in
      shape perception with a control condition where no noise was added. In the
      conditions where shape and surround stimuli were well defined, we found a shape
      contrast bias. When the surround stimuli were degraded, this contrast bias
      decreased. Most interestingly, when the central shape was degraded, an
      assimilation bias was observed. This bias was larger when the entire stimulus was
      degraded compared to when only the central shape was degraded. This suggests that
      shape contrast is the result of inference processes relying on local
      representations in early visual areas whereas assimilation is related to
      inference processes by global representations in higher visual areas.

PMID- 19757955
TI  - Estimated capacity of object files in visual short-term memory is not improved by
      retrieval cueing.
AB  - Visual short-term memory (VSTM) has been claimed to maintain three to five
      feature-bound object representations. Some results showing smaller capacity
      estimates for feature binding memory have been interpreted as the effects of
      interference in memory retrieval. However, change-detection tasks may not
      properly evaluate complex feature-bound representations such as triple
      conjunctions in VSTM. To understand the general type of feature-bound object
      representation, evaluation of triple conjunctions is critical. To test whether
      interference occurs in memory retrieval for complete object file representations
      in a VSTM task, we cued retrieval in novel paradigms that directly evaluate the
      memory for triple conjunctions, in comparison with a simple change-detection
      task. In our multiple object permanence tracking displays, observers monitored
      for a switch in feature combination between objects during an occlusion period,
      and we found that a retrieval cue provided no benefit with the triple conjunction
      tasks, but significant facilitation with the change-detection task, suggesting
      that low capacity estimates of object file memory in VSTM reflect a limit on
      maintenance, not retrieval.

PMID- 19757956
TI  - Binocular combination in anisometropic amblyopia.
AB  - Using a suprathreshold binocular summation paradigm developed by J. Ding and G.
      Sperling (2006, 2007) for normal observers, we investigated suprathreshold
      cyclopean perception in anisometropic amblyopia. In this paradigm, two
      suprathreshold sinewave gratings of the same spatial frequency but different
      spatial phases are presented to the left and right eyes of the observer. The
      perceived phase of the binocularly combined cyclopean image is measured as a
      function of the contrast ratio between the images in the two eyes. We found that
      both eyes contributed equally in normal subjects. However, stimulus of equal
      contrast was weighted much less in the amblyopic eye relative to the fellow eye
      in binocular combination. For the five amblyopes, the effective contrast of the
      amblyopic eye in binocular combination is equal to about 11%-28% of the same
      contrast presented to the fellow eye, much less than the ratio of contrast
      sensitivity between the two eyes (0.73-1.42). The results from the current study
      have many important implications in amblyopia research and treatment.

PMID- 19757957
TI  - Can illumination estimates provide the basis for color constancy?
AB  - Objects hardly appear to change color when the spectral distribution of the
      illumination changes: a phenomenon known as color constancy. Color constancy
      could either be achieved by relying on properties that are insensitive to changes
      in the illumination (such as spatial color contrast) or by compensating for the
      estimated chromaticity of the illuminant. We examined whether subjects can judge
      the illuminant's color well enough to account for their own color constancy. We
      found that subjects were very poor at judging the color of a lamp from the light
      reflected by the scene it illuminated. They were much better at judging the color
      of a surface within the scene. We conclude that color constancy must be achieved
      by relying on relationships that are insensitive to the illumination rather than
      by explicitly judging the color of the illumination.

PMID- 19757958
TI  - Impact of scattering and spherical aberration in contrast sensitivity.
AB  - We investigated the impact in spatial visual performance of the combined presence
      of different amounts of spherical aberration and intraocular scattering in the
      eye. In a group of subjects, contrast sensitivity at 6 cycles per degree was
      measured when viewing through holographic diffusers to produce different levels
      of scattering and with their spherical aberration simultaneously controlled using
      an adaptive-optics visual simulator. For elevated levels of scattering, the
      addition of small amounts of spherical aberration either does not decrease, or
      even may slightly increase, contrast sensitivity under some conditions. This
      seems to be due to an optical effect also demonstrated in an artificial eye.
      Although the visual effect is quite small, this finding could suggest a balancing
      mechanism where larger spherical aberration could keep relatively stable the
      retinal image quality under the presence of elevated scattering. This is actually
      the situation in older eyes with both spherical aberration and intraocular
      scatter being higher than in young eyes.

PMID- 19757959
TI  - Cross-orientation masking in human color vision.
AB  - Detection of a Gabor pattern is impaired in the presence of a similar pattern of
      orthogonal orientation, a phenomenon known as cross-orientation masking (XOM).
      Here we investigate the role of color in cross-orientation masking. We measured
      contrast detection thresholds to horizontally oriented Gabors overlaid by similar
      Gabors of a different orientation. Red-green chromatic masking was compared to
      achromatic masking for a wide range of spatial and temporal frequencies,
      orientations, and masks contrasts. We find that cross-orientation masking is
      significantly greater for chromatic than achromatic contrast. We also find it is
      invariant with the spatio-temporal conditions used, unlike achromatic cross
      orientation masking that is known to have a spatio-temporal dependence (greatest
      for low spatial frequencies at high temporal frequencies). Furthermore, chromatic
      masking is isotropic (invariant across the orientation difference between test
      and mask), whereas the achromatic version of the masking effect displays
      orientation tuning, a phenomenon that was originally used to indicate the
      presence of orientationally selective mechanisms in human vision. We conclude
      that the P cell pathway or its projections can support cross-orientation masking.
      We propose distinct physiological origins for chromatic and achromatic masking,
      with a predominantly cortical site for chromatic masking in contrast to the M
      cell subcortical influences on achromatic masking suggested by previous studies.

PMID- 19757960
TI  - Determination of foveal location using scanning laser polarimetry.
AB  - The fovea is the retinal location responsible for our most acute vision. There
      are several methods used to localize the fovea, but the fovea is not always
      easily identifiable. Landmarks used to determine the foveal location are variable
      in normal subjects and localization becomes even more difficult in instances of
      retinal disease. In normal subjects, the photoreceptor axons that make up the
      Henle fiber layer are cylindrical and the radial orientation of these fibers is
      centered on the fovea. The Henle fiber layer exhibits form birefringence, which
      predictably changes polarized light in scanning laser polarimetry imaging. In
      this study 3 graders were able to repeatably identify the fovea in 35 normal
      subjects using near infrared image types with differing polarization content.
      There was little intra-grader, inter-grader, and inter-image variability in the
      graded foveal position for 5 of the 6 image types examined, with accuracy
      sufficient for clinical purposes. This study demonstrates that scanning laser
      polarimetry imaging can localize the fovea by using structural properties
      inherent in the central macula.

PMID- 19757961
TI  - Spatial filtering versus anchoring accounts of brightness/lightness perception in
      staircase and simultaneous brightness/lightness contrast stimuli.
AB  - J. Cataliotti and A. Gilchrist (1995) reported that, consistent with anchoring
      theory, the lightness of a black step in a reflectance staircase was not altered
      by moving a white step from a remote to an adjacent location. Recently, E.
      Economou, S. Zdravkovic, and A. Gilchrist (2007) reported data supporting three
      additional predictions of the anchoring model (A. Gilchrist et al., 1999): 1)
      equiluminant incremental targets in staircase simultaneous lightness contrast
      stimuli appeared equally light; 2) the simultaneous lightness contrast effect was
      due mainly to the lightening of the target on the black surround; and 3) the
      strength of lightness induction was greatest for darker targets. We investigated
      similar stimuli using brightness/lightness matching and found, contrary to these
      reports, that: 1) the relative position of the steps in a luminance staircase
      significantly influenced their brightness/lightness; 2) equiluminant incremental
      targets in staircase simultaneous brightness/lightness contrast stimuli did not
      all appear equally bright/light; 3) an asymmetry due to a greater
      brightening/lightening of the target on the black surround was not general; and
      4) darker targets produced larger effects only when plotted on a log scale. In
      addition, the ODOG model (B. Blakeslee & M. E. McCourt, 1999) did an excellent
      job of accounting for brightness/lightness matching in these stimuli.

PMID- 19757962
TI  - Using graphical models to infer multiple visual classification features.
AB  - This paper describes a new model for human visual classification that enables the
      recovery of image features that explain performance on different visual
      classification tasks. Unlike some common methods, this algorithm does not explain
      performance with a single linear classifier operating on raw image pixels.
      Instead, it models classification as the result of combining the output of
      multiple feature detectors. This approach extracts more information about human
      visual classification than has been previously possible with other methods and
      provides a foundation for further exploration.

PMID- 19757963
TI  - Does gravity matter? Effects of semantic and syntactic inconsistencies on the
      allocation of attention during scene perception.
AB  - It has been shown that attention and eye movements during scene perception are
      preferentially allocated to semantically inconsistent objects compared to their
      consistent controls. However, there has been a dispute over how early during
      scene viewing such inconsistencies are detected. In the study presented here, we
      introduced syntactic object-scene inconsistencies (i.e., floating objects) in
      addition to semantic inconsistencies to investigate the degree to which they
      attract attention during scene viewing. In Experiment 1 participants viewed
      scenes in preparation for a subsequent memory task, while in Experiment 2
      participants were instructed to search for target objects. In neither experiment
      were we able to find evidence for extrafoveal detection of either type of
      inconsistency. However, upon fixation both semantically and syntactically
      inconsistent objects led to increased object processing as seen in elevated gaze
      durations and number of fixations. Interestingly, the semantic inconsistency
      effect was diminished for floating objects, which suggests an interaction of
      semantic and syntactic scene processing. This study is the first to provide
      evidence for the influence of syntactic in addition to semantic object-scene
      inconsistencies on eye movement behavior during real-world scene viewing.

PMID- 19757964
TI  - Slant cues are processed with different latencies for the online control of
      movement.
AB  - For the online control of movement, it is important to respond fast. The extent
      to which cues are effective in guiding our actions might therefore depend on how
      quickly they provide new information. We compared the latency to alter a movement
      when monocular and binocular cues indicated that the surface slant had changed.
      We found that subjects adjusted their movement in response to three types of
      information: information about the new slant from the monocular image,
      information about the new slant from binocular disparity, and information about
      the change in slant from the change in the monocular image. Responses to changes
      in the monocular image were approximately 40 ms faster than responses to a new
      slant estimate from binocular disparity and about 90 ms faster than responses to
      a new slant estimate from the monocular image. Considering these delays,
      adjustments of ongoing movements to changes in slant will usually be initiated by
      changes in the monocular image. The response will later be refined on the basis
      of combined binocular and monocular estimates of slant.

PMID- 19757965
TI  - Past rejections lead to future misses: selection-related inhibition produces
      blink-like misses of future (easily detectable) events.
AB  - Our recent experiences can have substantial effects on our future behavior. Here
      we show influences of prior visual experiences on the future workings of
      selective attention. Selective attention uses inhibitory processes to suppress
      distracting information on a given trial. We show that, once in place, this
      selective inhibition persists across trials and leads to misses of future targets
      when they belong to the previously distracting category of stimuli. This effect
      is documented using a single-target RSVP task, in which participants are asked to
      report the case (or color) of an oddball target. Furthermore, we show that
      selective inhibition is not present when observers are merely asked to detect the
      presence or absence of the oddball target. We argue that selective inhibition is
      a mechanism aimed at facilitating the access to secondary (non-target defining)
      features of the target stimuli, and that our results provide further evidence
      that visual stimuli are processed in a hierarchical, non-holistic manner.

PMID- 19757966
TI  - The pupils and optical systems of gecko eyes.
AB  - The nocturnal helmet gecko, Tarentola chazaliae, discriminates colors in dim
      moonlight when humans are color blind. The sensitivity of the helmet gecko eye
      has been calculated to be 350 times higher than human cone vision at the color
      vision threshold. The optics and the large cones of the gecko are important
      reasons why they can use color vision at low light intensities. Using
      photorefractometry and an adapted laboratory Hartmann-Shack wavefront sensor of
      high resolution, we also show that the optical system of the helmet gecko has
      distinct concentric zones of different refractive powers, a so-called multifocal
      optical system. The intraspecific variation is large but in most of the
      individuals studied the zones differed by 15 diopters. This is of the same
      magnitude as needed to focus light of the wavelength range to which gecko
      photoreceptors are most sensitive. We compare the optical system of the helmet
      gecko to that of the diurnal day gecko, Phelsuma madagascariensis grandis. The
      optical system of the day gecko shows no signs of distinct concentric zones and
      is thereby monofocal.

PMID- 19757967
TI  - Contributions of form, motion and task to biological motion perception.
AB  - The ability of human observers to detect 'biological motion' of humans and
      animals has been taken as evidence of specialized perceptual mechanisms. This
      ability remains unimpaired when the stimulus is reduced to a moving array of dots
      representing only the joints of the agent: the point light walker (PLW) (G.
      Johansson, 1973). Such stimuli arguably contain underlying form, and recent
      debate has centered on the contributions of form and motion to their processing
      (J. O. Garcia & E. D. Grossman, 2008; E. Hiris, 2007). Human actions contain
      periodic variations in form; we exploit this by using brief presentations to
      reveal how these natural variations affect perceptual processing. Comparing
      performance with static and dynamic presentations reveals the influence of
      integrative motion signals. Form information appears to play a critical role in
      biological motion processing and our results show that this information is
      supported, not replaced, by the integrative motion signals conveyed by the
      relationships between the dots of the PLW. However, our data also suggest strong
      task effects on the relevance of the information presented by the PLW. We discuss
      the relationship between task performance and stimulus in terms of form and
      motion information, and the implications for conclusions drawn from PLW based
      studies.

PMID- 19757968
TI  - Influence of visual path information on human heading perception during rotation.
AB  - How does visual path information influence people's perception of their
      instantaneous direction of self-motion (heading)? We have previously shown that
      humans can perceive heading without direct access to visual path information.
      Here we vary two key parameters for estimating heading from optic flow, the field
      of view (FOV) and the depth range of environmental points, to investigate the
      conditions under which visual path information influences human heading
      perception. The display simulated an observer traveling on a circular path.
      Observers used a joystick to rotate their line of sight until deemed aligned with
      true heading. Four FOV sizes (110 x 94 degrees, 48 x 41 degrees, 16 x 14 degrees,
      8 x 7 degrees) and depth ranges (6-50 m, 6-25 m, 6-12.5 m, 6-9 m) were tested.
      Consistent with our computational modeling results, heading bias increased with
      the reduction of FOV or depth range when the display provided a sequence of
      velocity fields but no direct path information. When the display provided path
      information, heading bias was not influenced as much by the reduction of FOV or
      depth range. We conclude that human heading and path perception involve separate
      visual processes. Path helps heading perception when the display does not contain
      enough optic-flow information for heading estimation during rotation.

PMID- 19757970
TI  - Flower power.

PMID- 19757969
TI  - On the automaticity and flexibility of covert attention: a speed-accuracy trade
      off analysis.
AB  - Exogenous covert attention improves discriminability and accelerates the rate of
      visual information processing (M. Carrasco & B. McElree, 2001). Here we
      investigated and compared the effects of both endogenous (sustained) and
      exogenous (transient) covert attention. Specifically, we directed attention via
      spatial cues and evaluated the automaticity and flexibility of exogenous and
      endogenous attention by manipulating cue validity in conjunction with a response
      signal speed-accuracy trade-off (SAT) procedure, which provides conjoint measures
      of discriminability and information accrual. To investigate whether
      discriminability and rate of information processing differ as a function of cue
      validity (chance to 100%), we compared how both types of attention affect
      performance while keeping experimental conditions constant. With endogenous
      attention, both the observed benefits (valid-cue) and the costs (invalid-cue)
      increased with cue validity. However, with exogenous attention, the benefits and
      costs in both discriminability and processing speed were similar across cue
      validity conditions. These results provide compelling time-course evidence that
      whereas endogenous attention can be flexibly allocated according to cue validity,
      exogenous attention is automatic and unaffected by cue validity.

PMID- 19757971
TI  - Does moderate fruit and vegetable intake protect against frequent mental distress
      in adult primary care patients?

PMID- 19757972
TI  - The antifungal activity of urine after ingestion of cranberry products.

PMID- 19757973
TI  - Altering the acid/alkaline balance of water via the use of an intention-host
      device.
AB  - BACKGROUND: The research presented in this article has satisfactorily followed
      the earlier protocols of the last 2 authors and has successfully replicated their
      earlier work, which utilized an intention-host device to increase the pH of
      highly purified water in equilibrium with air by approximately +1 pH units at
      room temperature with no intentional chemical additions. METHODS: In addition,
      the present experimental research, by the first 2 authors, breaks important new
      ground by revealing examples of both (1) different time-dependent pH-profiles
      than found in the earlier work and (2) a very nontraditional order of chemical
      like reaction kinetics than has heretofore been observed. CONCLUSIONS: The time
      dependence behavior of these reaction sequences support the hypothesis that such
      intention-host devices can produce a significant measure of coupling between two
      uniquely different, and normally noninteracting, levels of physical reality that
      exhibit a reciprocal-type of substance behavior.

PMID- 19757974
TI  - T'ai chi and qigong for health: patterns of use in the United States.
AB  - BACKGROUND: Little is known in the United States about those who practice t'ai
      chi and qigong, two mind-body techniques that originated in Asia. OBJECTIVE: The
      objective of this study is to characterize use of t'ai chi and qigong for health
      with regard to sociodemographics, health status, medical conditions, perceptions
      of helpfulness, and disclosure of use to medical professionals. METHODS: We
      analyzed associations of t'ai chi and qigong use for health using cross-sectional
      data from the 2002 National Health Interview Survey (NHIS) Alternative Medicine
      Supplement (n = 31,044). The 2002 NHIS estimated the number of t'ai chi and
      qigong users for health to be 2.5 and 0.5 million persons, respectively. We
      collapsed t'ai chi and qigong use into a single category (TCQ) for analysis,
      representing 2.8 million individuals. RESULTS: We found that neither age nor sex
      was associated with TCQ use. TCQ users were more likely than nonusers to be Asian
      than white (odds ratio [OR] 2.02, 95% confidence interval [CI] 1.30-3.15),
      college educated (OR 2.44, 95% CI 1.97-3.03), and less likely to live in the
      Midwest (OR 0.64, 95% CI 0.42-0.96) or the southern United States (OR 0.51, 95%
      CI 0.36-0.72) than the West. TCQ use was associated independently with higher
      reports of musculoskeletal conditions (OR 1.43, 95% CI 1.11-1.83), severe sprains
      (OR 1.65, 95% CI 1.14-2.40), and asthma (OR 1.50, 95% CI 1.08-2.10). Half of TCQ
      users also used yoga for health in the last 12 months. Most TCQ users reported
      their practice to be important to maintain health, but only a quarter of users
      disclosed their practice to a medical professional. CONCLUSIONS: In the United
      States, TCQ is practiced for health by a diverse population, and users report
      benefits for maintaining health. Further research is needed to establish efficacy
      and safety for target populations, including those with musculoskeletal and
      pulmonary disease, as well as for preventive health.

PMID- 19757975
TI  - Endocrinological evaluations of brief hand massages in palliative care.
AB  - BACKGROUND AND OBJECTIVES: Some patients with advanced cancer make use of
      complementary therapies for the reduction of anxiety and stress. These patients
      can suffer distressing end-of-life symptoms, which conventional treatments might
      not relieve satisfactorily. Although previous studies have suggested that
      complementary therapies could be useful for reducing distress in patients with
      cancer, it has remained unclear whether these benefits are applicable at the end
      of-life stage. The current study examined to validate salivary chromogranin A
      (CgA) as a biomarker for relieving stress by hand massage in terminally ill
      patients. METHODS: The study group comprised 34 inpatients in palliative care
      units. Each of these patients received a 5-minute massage to the upper extremity.
      Before and after the massage, saliva samples were collected in order to measure
      the CgA levels. RESULTS: The brief hand massage appears to reduce levels of
      stress according to the salivary CgA (p < 0.05). In addition, we found
      statistically significant changes in patient satisfaction with hand massage.
      CONCLUSIONS: Salivary CgA could potentially be used as a biomarker to measure
      relieving stress by hand massage in a palliative-care setting.

PMID- 19757976
TI  - Religion, clinicians, and the integration of complementary and alternative
      medicines.
AB  - OBJECTIVE: The aim of this study was to compare religious characteristics of
      general internists, rheumatologists, naturopaths, and acupuncturists, as well as
      to examine associations between physicians' religious characteristics and their
      openness to integrating complementary and alternative medicine (CAM). DESIGN: The
      design involved a national mail survey. The subjects were internists,
      rheumatologists, naturopaths, and acupuncturists. MEASURES: Physician outcome
      measures were use of and attitudes toward six classes of CAM. Predictors were
      religious affiliation, intrinsic religiosity, spirituality, and religious
      traditionalism. RESULTS: There was a 65% response. Naturopaths and acupuncturists
      were three times as likely as internists and rheumatologists to report no
      religious affiliation (35% versus 12%, p < 0.001), but were more likely to
      describe themselves as very spiritual (51% versus 20%, p < 0.001) and to agree
      they try to carry religious beliefs into life's dealings (51% versus 44%, p <
      0.01). Among physicians, increased spirituality and religiosity coincided with
      more personal use of CAM and willingness to integrate CAM into a treatment
      program. CONCLUSIONS: Current and future integrative medicine will be shaped in
      part by religious and spiritual characteristics of providers.

PMID- 19757977
TI  - Evidence from the Cochrane Collaboration for Traditional Chinese Medicine
      therapies.
AB  - BACKGROUND: The Cochrane Collaboration, an international not-for-profit
      organization that prepares and maintains systematic reviews of randomized trials
      of health care therapies, has produced reviews summarizing much of the evidence
      on Traditional Chinese Medicine (TCM). Our objective was to review the evidence
      base according to Cochrane systematic reviews. METHODS: In order to detect
      reviews focusing on TCM, we searched the titles and abstracts of all reviews in
      Issue 4, 2008 of the Cochrane Database of Systematic Reviews. For each review, we
      extracted data on the number of trials included and the total number of
      participants. We provided an indication of the strength of the review findings by
      assessing the reviewers' abstract conclusions statement. We supplemented our
      assessment of the abstract conclusions statements with a listing of the
      comparisons and outcomes showing statistically significant meta-analyses results.
      RESULTS: We identified 70 Cochrane systematic reviews of TCM, primarily
      acupuncture (n = 26) and Chinese herbal medicine (n = 42), and 1 each of
      moxibustion and t'ai chi. Nineteen (19) of 26 acupuncture reviews and 22/42
      herbal medicine reviews concluded that there was not enough good quality trial
      evidence to make any conclusion about the efficacy of the evaluated treatment,
      while the remaining 7 acupuncture and 20 herbal medicine reviews and each of the
      moxibustion and t'ai chi reviews indicated a suggestion of benefit, which was
      qualified by a caveat about the poor quality and quantity of studies. Most
      reviews included many distinct interventions, controls, outcomes, and
      populations, and a large number of different comparisons were made, each with a
      distinct forest plot. CONCLUSIONS: Most Cochrane systematic reviews of TCM are
      inconclusive, due specifically to the poor methodology and heterogeneity of the
      studies reviewed. Some systematic reviews provide preliminary evidence of Chinese
      medicine's benefits to certain patient populations, underscoring the importance
      and appropriateness of further research. These preliminary findings should be
      considered tentative and need to be confirmed with rigorous randomized controlled
      trials.

PMID- 19757978
TI  - Integration of acupuncture into family medicine teaching clinics.
AB  - OBJECTIVES: As growing numbers of patients use complementary and alternative
      medicine (CAM), improvement is needed in communication between providers of CAM
      and allopathic medicine. This study describes collaborative acupuncture clinics
      (CACs) run by providers from Oregon Health and Science University (OHSU) and the
      Oregon College of Oriental Medicine (OCOM) in the setting of family medicine
      teaching clinics. It examines patient demographics, quality of education for
      medical learners, referral practices of primary care physicians (PCPs), and
      quality of communication between acupuncturists and PCPs at these clinics.
      DESIGN: Demographic data were abstracted from electronic medical records of
      patients treated at least three times in the CACs between 2006 and 2007. A survey
      on quality of education at the CACs was given to acupuncture interns, medical
      students, and acupuncture supervisors. A separate survey collected information
      from PCPs at the family medicine clinics regarding referral practices to
      acupuncture and quality of communication between PCPs and acupuncturists.
      RESULTS: Of the 96 patients seen at the clinics, 74% were female, 76% were
      European-American, and the mean age was 45.9 years. Sixty-one percent (61%) of
      patients were insured through private insurance, 31.3% had Medicare or Medicaid,
      and 7.3% did not have insurance. Most of the 51 acupuncture providers who
      responded were satisfied with the quality of education at the CACs. Eighty
      percent of responding PCPs had referred at least one patient to the CACs. The
      majority of referrals was for a pain condition. Most PCPs would find a summary of
      the acupuncture visit helpful. Referral practices to different modalities were
      most influenced by patient interest and physician's belief in whether or not the
      modality would help. CONCLUSIONS: Demographics of patients at the CACs were
      comparable to those of patients seen in other acupuncture clinics. The
      collaborative structure of the CACs allowed for a unique learning experience and
      improved communication between providers of CAM and conventional medicine.

PMID- 19757979
TI  - Pattern differentiation in Traditional Chinese Medicine can help define specific
      indications for biomedical therapy in the treatment of rheumatoid arthritis.
AB  - OBJECTIVES: The objective of this study is to explore the role of Traditional
      Chinese Medicine (TCM) pattern differentiation in identifying a subset of
      patients with rheumatoid arthritis (RA) who are more likely to respond to
      biomedical combination therapy. METHODS: This study uses data from a previous
      multicenter randomized-controlled clinical trial. One hundred and ninety-four
      (194) patients were treated with biomedical combination therapy (diclofenac,
      methotrexate, and sulfasalazine). ACR20 response at 12 weeks and 24 weeks was
      used for evaluation of efficacy. Eight (8) symptoms, which are the most important
      for establishing TCM cold and hot patterns in patients with RA, were analyzed in
      this study. TCM patterns were obtained using factor analysis of the eight
      symptoms. Thirst, vexation, hot feeling in the joints, turbid yellow-colored
      urine, and fever were classified as factor 1. Cold feeling in the whole body,
      cold feeling in the limbs, and cold feeling in the joints were classified as
      factor 2. The classification into factor 1 and 2 is similar to TCM hot pattern
      and cold pattern differentiation, since the symptoms in factor 1 and 2 are the
      key symptoms in TCM hot and cold patterns, respectively. The effective rates in
      patients with different TCM patterns were analyzed with the chi(2) method.
      RESULTS: At 12 weeks, ACR20 response in patients treated with the biomedical
      combination therapy was 36.08%. At 24 weeks, ACR20 response was 69.59%. Based on
      the eight symptoms used in factor analysis, the effective rates in the patients
      with cold pattern and hot pattern were 51.67% and 29.09%, respectively, after 12
      weeks of treatment; and 88.52% and 55.36%, respectively, after 24 weeks of
      treatment. CONCLUSIONS: TCM pattern differentiation based on symptoms can help
      identify a subset of patients with RA that will more likely respond to biomedical
      therapy, consisting of diclofenac, methotrexate, and sulfasalazine.

PMID- 19757980
TI  - Acupressure therapy inhibits the development of diabetic complications in Chinese
      patients with type 2 diabetes.
AB  - OBJECTIVES: The objectives of this study were to investigate the effects of
      acupressure therapy (AT) on the development and progression of diabetic
      complications in Chinese patients with type 2 diabetes (T2D). DESIGN AND METHODS:
      A total of 80 patients with T2D were recruited for a randomized clinical study of
      the effect of AT on the progression and development of diabetic complications,
      and 64 patients were followed up for 3 years. All patients with T2D were treated
      with regular medicines and participated in diet and exercise programs for the
      control of hyperglycemia and hypertension. The patients in the AT group received
      additional treatment of a 90-minute AT 4-6 times per week for 3 consecutive
      years. Their blood lipids, fasting glucose levels, and heart and kidney functions
      and nerve conduction velocity (NCV) were longitudinally monitored before and
      every 12 months after AT. RESULTS: Following AT therapy for 3 years,
      significantly lower levels of total cholesterol, triglycerides, low-density
      lipoprotein-cholesterol, and higher levels of high-density lipoprotein
      cholesterol (HDL-C) were observed and no significantly increased levels of serum
      creatinine and urine protein were detected in the AT group, as compared with that
      in controls. Furthermore, the mean values of NCV in the AT group at 2 years post
      treatment were significantly greater than those of controls and were further
      elevated at the end of this study. Therefore, AT inhibited the progression of
      hyperlipidemia and improved diabetes-associated kidney function and neuropathy in
      Chinese patients with T2D. CONCLUSIONS: AT may be an effective nonpharmacological
      adjunctive strategy for alleviating the development and progression of T2D
      related complications.

PMID- 19757981
TI  - Resolving paradoxes in acupuncture research: a roundtable discussion.

PMID- 19757982
TI  - Effects of a combination of Hypericum perforatum and Vitex agnus-castus on PMS
      like symptoms in late-perimenopausal women: findings from a subpopulation
      analysis.
AB  - BACKGROUND: It has been suggested that some of the symptoms typically attributed
      to menopause may be more related to premenstrual syndrome (PMS) than menopause,
      as perimenopausal women appear to be more prone to PMS-like symptoms, or at least
      to tolerate them less well. OBJECTIVE: The objective of this study was to
      evaluate the effectiveness of a phytotherapeutic intervention comprising a
      combination of Hypericum perforatum (St. John's wort) and Vitex agnus-castus
      (chaste tree/berry) in the management of PMS-like symptoms in perimenopausal
      women. DESIGN: A double-blind, randomized, placebo-controlled parallel trial was
      conducted over 16 weeks on menopause-related symptoms. Data on PMS-like symptoms
      were collected at 4-weekly intervals from a small subgroup of late-perimenopausal
      women (n = 14) participating in this study. The primary endpoint was PMS scores
      measured on the Abrahams Menstrual Symptoms Questionnaire, comprising the
      subclusters of PMS-A (anxiety), PMS-D (depression), PMS-H (hydration), and PMS-C
      (cravings). Herbal combination therapy or placebo tablets were administered twice
      daily. RESULTS: At the end of the 16-week treatment phase, analyses of covariance
      showed the herbal combination to be superior to placebo for total PMS-like scores
      (p = 0.02), PMS-D (p = 0.006), and PMS-C clusters (p = 0.027). The active
      treatment group also showed significant reductions in the anxiety (p = 0.003) and
      hydration (p = 0.002) clusters, using paired-samples t tests. Results of trend
      analyses showed significant treatment group effects across the five phases for
      total PMS and all subscales, all in the clinically expected direction. No
      significant trends were evident in the placebo group. CONCLUSIONS: These results
      suggest a potentially significant clinical application for this phytotherapeutic
      combination in PMS-like symptoms among perimenopausal women. Further research is
      warranted through a randomized, controlled trial dedicated to investigation of
      these symptoms.

PMID- 19757983
TI  - Notice of retraction.

PMID- 19757984
TI  - Prevalence of COPD among symptomatic patients in a primary care setting.
AB  - OBJECTIVE: Spirometry is recognized as the gold standard assessment for the
      diagnosis of COPD. However, spirometry continues to be underused, perpetuating
      the underdiagnosis of COPD. The aim of this study was to evaluate the prevalence
      of COPD in a primary care setting in patients with a smoking history and self
      reported chronic bronchitis symptoms. RESEARCH DESIGN AND METHODS: This was a
      multi-center, cross-sectional study. The primary assessment was the percentage of
      patients with airway obstruction (post-bronchodilator FEV(1)/FVC ratio < or =
      0.70) compared to those without obstruction (post-bronchodilator FEV(1)/FVC ratio
      > 0.70). RESULTS: Airflow obstruction consistent with COPD was confirmed in 26%
      of patients (mean age 52.9 years, FEV(1) 81.4% predicted and smoking history 39.8
      pack-years) that reported chronic bronchitis symptoms. Airflow obstruction
      increased with age and smoking history. Slight or moderate dyspnea was reported
      by 68% of patients and the majority had not talked to their doctor about cough
      and continued to smoke. LIMITATIONS: Patients were evaluated at a single visit.
      The definition of airway obstruction used may have lead to overdiagnosis in
      patients aged 70 and older. CONCLUSION: This study confirms that many patients
      with COPD remain undiagnosed in the primary care setting. Evaluation of
      spirometry in patients with a smoking history and chronic bronchitis symptoms can
      aid in the diagnosis of COPD, allowing earlier treatment thereby reducing the
      burden of this debilitating disease. CLINICAL TRIAL REGISTRATION: Study code
      ADC109043; clinicaltrials.gov #NCT00442468.

PMID- 19757985
TI  - Impact of delaying 5-alpha reductase inhibitor therapy in men on alpha-blocker
      therapy to treat BPH: assessment of acute urinary retention and prostate-related
      surgery.
AB  - OBJECTIVE: Pharmacologic treatment of lower urinary tract symptoms from benign
      prostatic hyperplasia (BPH) commonly includes alpha-blockers (ABs) and 5alpha
      reductase inhibitors (5ARIs). Many clinicians use ABs for rapid symptom control
      and 5ARIs to modify long-term disease progression. The purpose of this study was
      to assess the clinical impact of delayed 5ARI therapy in patients treated with AB
      for lower urinary tract symptoms. RESEARCH DESIGN AND METHODS: Using two
      nationally representative databases, two retrospective analyses were conducted
      including patients aged > or =50 years treated for BPH between 2000 and 2007.
      Clinical outcomes for those using add-on 5ARI therapy early (within 30 days of
      initiating AB) and late (>30 days after initiating AB) were compared. Likelihood
      of clinical progression, defined as the presence of acute urinary retention (AUR)
      and prostate surgery, was assessed over 1 year after AB initiation, and modeled
      as a function of the treatment cohorts and the following baseline covariates:
      AUR, BPH stage, Charlson Comorbidity Index, age, and number of unique diagnosis
      codes, unique non-BPH-related classes of prescriptions filled, and specialty
      care. RESULTS: Of 6896 men included in the analyses, approximately 60% initiated
      5ARI therapy within 30 days of AB therapy (the early cohort). Patients in the
      early cohort were less likely to have clinical progression. Each 30-day delay in
      starting 5ARIs resulted in an increased likelihood of overall clinical
      progression (average 21.1%), AUR (average 18.6%), and prostate-related surgery
      (average 26.7%). CONCLUSIONS: These results suggest that delaying 5ARI therapy in
      men with BPH increases the risk of AUR and prostate surgery. LIMITATIONS:
      Confounding factors, such as symptom severity and prostate volume, may have
      influenced the findings of the study.

PMID- 19757987
TI  - Effects of metal compounds with distinct physicochemical properties on iron
      homeostasis and antibacterial activity in the lungs: chromium and vanadium.
AB  - In situ reactions of metal ions or their compounds are important mechanisms by
      which particles alter lung immune responses. The authors hypothesized that major
      determinants of the immunomodulatory effect of any metal include its redox
      behavior/properties, oxidation state, and/or solubility, and that the toxicities
      arising from differences in physicochemical parameters are manifest, in part, via
      differential shifts in lung iron (Fe) homeostasis. To test the hypotheses,
      immunomodulatory potentials for both pentavalent vanadium (VV; as soluble
      metavanadate or insoluble vanadium pentoxide) and hexavalent chromium (CrVI; as
      soluble sodium chromate or insoluble calcium chromate) were quantified in rats
      after inhalation (5h/day for 5 days) of each at 100 microg metal/m3. Differences
      in effects on local bacterial resistance between the two VV, and between each
      CrVI, agents suggested that solubility might be a determinant of in situ
      immunotoxicity. For the soluble forms, VV had a greater impact on resistance than
      CrVI, indicating that redox behavior/properties was likely also a determinant.
      The soluble VV agent was the strongest immunomodulant. Regarding Fe homeostasis,
      both VV agents had dramatic effects on airway Fe levels. Both also impacted local
      immune/airway epithelial cell Fe levels in that there were significant increases
      in production of select cytokines/chemokines whose genes are subject to
      regulation by HIF-1 (whose intracellular longevity is related to cell Fe status).
      Our findings contribute to a better understanding of the role that metal compound
      properties play in respiratory disease pathogenesis and provide a rationale for
      differing pulmonary immunotoxicities of commonly encountered ambient metal
      pollutants.

PMID- 19757988
TI  - The physics of oxygen delivery: facts and controversies.

PMID- 19757989
TI  - Epilepsy and insular Grade II gliomas: an interdisciplinary point of view from a
      retrospective monocentric series of 46 cases.
AB  - OBJECT: There are few data in the literature concerning a multimodal approach to
      insular WHO Grade II gliomas (GIIGs) and the control of epilepsy after treatment.
      In this paper, the authors describe a monocentric series of 46 cases in which
      patients underwent various sequential treatments for insular GIIGs. On the basis
      of global results with regard to epilepsy, the respective interests in the
      various treatments are discussed. METHODS: Available data on 46 patients
      harboring insular GIIGs were extracted from a local database of 288 GIIGs. The
      various therapeutic sequences were analyzed in parallel with the course of
      seizure frequency. RESULTS: Despite the usual difficulties with seizure
      quantification in retrospective studies, the authors showed that 1) the negative
      course of seizure frequency was mostly connected to tumor progression, 2) surgery
      almost always had a favorable effect on epilepsy, and 3) chemotherapy had a
      mostly favorable effect with acceptable tolerance. The authors were unable to
      draw conclusions about the role of radiotherapy given the too few cases.
      CONCLUSIONS: This extensive experience with insular GIIGs tends to confirm
      interest in their surgical removal and supports interest in chemotherapy from an
      epileptological point of view.

PMID- 19757990
TI  - Id proteins facilitate self-renewal and proliferation of neural stem cells.
AB  - Members of helix-loop-helix (HLH) protein family of Id (inhibitor of
      differentiation) dimerize with bHLH transcription factors and function as
      negative regulators of differentiation during development. Most of inhibitory
      roles of Id proteins have been demonstrated in non-neural tissues, and their
      roles in the developing nervous system are not clearly demonstrated. In this
      study, we show that Id1, Id2, and Id3 increase self-renewing and proliferation
      potential of cortical neural stem cells (NSCs) while inhibiting neuronal
      differentiation. In electrophoretic mobility gel shift and luciferase assays, Id
      proteins interfered with binding of NeuroD/E47 complexes to the E-box sequences
      and inhibited E-box-mediated gene expression. Overexpression of Id proteins in
      NSCs increased both the number and the size of neurospheres in colony-forming
      assays. Expression of Hes1 and Hes5 was not increased by overexpression of Id
      proteins under the condition in which Nestin expression was increased. In utero
      electroporation of Id yielded higher numbers of Ki67-positive and Sox2-positive
      cells in the mouse embryonic brain. The study suggests Id proteins play
      independent roles in the maintenance of neural stem properties.

PMID- 19757991
TI  - Transcriptional profiling of human embryonic stem cells differentiating to
      definitive and primitive endoderm and further toward the hepatic lineage.
AB  - Human embryonic stem cells (hESC) can differentiate into a variety of specialized
      cell types, and they constitute a useful model system to study embryonic
      development in vitro. In order to fully utilize the potential of these cells, the
      mechanisms that regulate the developmental processes of specific lineage
      differentiation need to be better defined. The aim of this study was to explore
      the molecular program involved in the differentiation of hESC toward definitive
      endoderm (DE) and further into the hepatic lineage, and to compare that with
      primitive endoderm (PrE) differentiation. To that end, we applied two protocols:
      a specific DE differentiation protocol and an intrinsic differentiation protocol
      that mainly mediates PrE formation. We collected hESC, hESC-derived DE, DE
      derived hepatocyte-progenitors (DE-Prog), DE-derived hepatocyte-like cells (DE
      Hep), and the corresponding PrE derivatives. The samples were analyzed using
      microarrays, and we identified sets of genes that were exclusively up-regulated
      in DE derivatives (compared to PrE derivatives) at discrete developmental stages.
      We also investigated known protein interactions among the set of up-regulated
      genes in DE-Hep. The results demonstrate important differences between DE and PrE
      differentiation on the transcriptional level. In particular, our results identify
      a unique molecular program, exclusively activated during development of DE and
      the subsequent differentiation of DE toward the hepatic lineage. We identified
      key genes and pathways of potential importance for future efforts to improve
      hepatic differentiation from hESC. These results reveal new opportunities for
      rational design of specific interventions with the purpose of generating enriched
      populations of DE derivatives, including functional hepatocytes.

PMID- 19757992
TI  - Finegoldia magna: a forgotten pathogen in prosthetic joint infection rediscovered
      by molecular biology.
AB  - In this study, we describe 13 patients with prosthetic infections due to
      Finegoldia magna (2% of our tested series). Patients presented with either
      polymicrobial infection after an open fracture or nosocomial infection after
      recent prosthesis implantation. Molecular techniques are critical for diagnosis,
      and recommended antibiotic prophylaxis has poor activity against F. magna.

PMID- 19757993
TI  - Switch from enfuvirtide to raltegravir in virologically suppressed multidrug
      resistant HIV-1-infected patients: a randomized open-label trial.
AB  - BACKGROUND: Among patients with multidrug-resistant human immunodeficiency virus
      type 1 (HIV-1) infection, salvage regimens including enfuvirtide have
      demonstrated sustained efficacy. Because of reluctance to use subcutaneous
      injections, raltegravir may be an alternative to replace enfuvirtide within a
      suppressive regimen. We conducted a prospective, randomized, open-label trial to
      compare the antiviral efficacy and safety of a switch to raltegravir with the
      efficacy and safety of continuing enfuvirtide. METHODS: A total of 170 patients
      with multidrug-resistant HIV-1 infection and plasma HIV-1 RNA levels <400
      copies/mL who were receiving enfuvirtide-based regimens were randomized 1:1 to
      maintain enfuvirtide or to switch to raltegravir. The primary efficacy end point
      was the cumulative proportion of patients with virologic failure, defined as a
      confirmed plasma HIV-1 RNA level >or=400 copies/mL, over 24 weeks. The secondary
      end points mainly involved safety. RESULTS: The switch to raltegravir was non
      inferior to the maintenance of enfuvirtide, with virologic failure rates of 1.2%
      in both treatment arms in the intention-to-treat analysis (beta = 0.01%; 95%
      confidence interval, -6.7 to 6.8) and 1.2% and 0%, respectively, in the on
      treatment analysis (beta = 1.22%; 95% confidence interval, -5.6 to 8.1). At week
      24, 88%-89% of patients in both arms had plasma HIV-1 RNA levels <50 copies/mL.
      No significant CD4 cell count changes occurred in either arm. Grade 3-4 adverse
      events and laboratory abnormalities were uncommon and were not different between
      the treatment arms. CONCLUSION: A switch to raltegravir was safe, well tolerated,
      and virologically non-inferior to the maintenance of enfuvirtide in patients
      infected with multidrug-resistant HIV-1 infection who were receiving suppressive
      antiretroviral therapy. CLINICAL TRIALS REGISTRATION: NCT00454337

PMID- 19757994
TI  - Research ethics and infection control.
AB  - The Keystone study of prevention of catheter-related infections in intensive care
      units raised important issues regarding infection control and research ethics.
      Infection control is an area common to public health and quality improvement. The
      performance of surveillance, the reporting of infection control data, and the
      response to complaints are all obligations raised by the international health
      regulations. The regulatory system around research ethics focuses on the
      individual subject in research and is not designed around areas such as infection
      control. Scientific methods are common to both infection control and research;
      both may result in "generalizable knowledge." Infection control physicians should
      work with their institutional review boards to try to streamline the process of
      ethics review. Regulatory change may be desirable to define and limit what
      infection control activities are construed as research.

PMID- 19757995
TI  - Sexual selection and the random union of gametes: testing for a correlation in
      fitness between mates in Drosophila melanogaster.
AB  - Both males and females vary in fitness. While high-fitness males typically have
      greater siring success, it is not clear whether these males sire an equal
      fraction of offspring from all females or a disproportionately large fraction
      with high-fitness females. The latter nonrandom reproductive pattern can arise as
      the result of sexual selection and creates a positive correlation in fitness
      between mates. Such a correlation, if it reflects a positive genetic correlation
      between mates with respect to fitness, increases the efficiency of selection,
      reducing mutation load and speeding adaptation. While there is evidence from many
      taxa that assortative mating for fitness may occur, these studies typically focus
      on observed matings rather than realized reproductive output. Here, we examine
      assortative mating for fitness in Drosophila melanogaster, first in the context
      of virgin matings and then using a measure of realized reproduction that
      incorporates remating and postcopulatory processes. We find evidence for positive
      assortative mating among virgins but no evidence of assortative mating using the
      more complete measure of reproduction.

PMID- 19757996
TI  - Cell delivery using an injectable and adhesive transglutaminase-gelatin gel.
AB  - In this study, we developed an injectable gelatin-transglutaminase (TGase) gel
      for cell delivery. The procedure provides a minimally invasive approach to
      deliver cells into tissue in a manner that improves localization. The results
      indicate gelatin-TGase to be noncytotoxic and to have adhesive properties that
      help localize and prevent the scattering of the cells after delivery. The in situ
      crosslinking between gelatin chains and endogenous collagen can create a strong
      attachment between the gel and tissue extracellular matrix, preventing cells from
      dissipation. The gelatin-TGase was also shown to maintain the carried cells to be
      viable and proliferative. Finally, through the adjustment of the enzymatic
      crosslinker concentration, the release rate of the cells into the surrounding
      tissue after injection was demonstrated to be controllable.

PMID- 19757998
TI  - Sclerostin and the unloading of bone.

PMID- 19758090
TI  - Aggressive behavior and performance in the Tegu lizard Tupinambis merianae.
AB  - Aggression is an important component of behavior in many animals and may be
      crucial to providing individuals with a competitive advantage when resources are
      limited. Although much is known about the effects of catecholamines and hormones
      on aggression, relatively few studies have examined the effects of physical
      performance on aggression. Here we use a large, sexually dimorphic teiid lizard
      to test whether individuals that show high levels of physical performance (bite
      force) are also more aggressive toward a potential threat (i.e., a human
      approaching the lizard). Our results show that independent of their sex, larger
      individuals with higher bite forces were indeed more aggressive. Moreover, our
      data show that individuals with higher bite forces tend to show decreased escape
      responses and are slower, providing evidence for a trade-off between fight and
      flight abilities. As bite force increased dramatically with body size, we suggest
      that large body size and bite force may reduce the threshold for an individual to
      engage in an aggressive encounter, allowing it to potentially gain or maintain
      resources and fight off predators while minimizing the risk of injury.

PMID- 19758091
TI  - Muscle metabolic capacities and plasma cortisol levels of the male three-spine
      stickleback Gasterosteus aculeatus: are there "femme fatale" or "macho male"
      effects?
AB  - To evaluate whether decreases in muscle metabolic capacities and increases in
      plasma cortisol explain the effects of neighboring conspecifics on male three
      spine sticklebacks Gasterosteus aculeatus, we housed mature males alone, with a
      mature female, or with a rival mature male. The neighbors were separated from the
      focal male by a partition that allowed him to smell, see, and hear his neighbor.
      In the first experiment, focal males were allowed to reproduce, whereas in the
      second experiment, no reproduction occurred. Coloration and behaviors were
      monitored while the males tended their nests (or for the same period in the
      second experiment). The presence of a neighbor markedly affected the reproductive
      coloration of the focal male, with solitary males being less colorful than males
      housed with a rival male or a female. Solitary males showed greater aggression
      toward a model male stickleback than did males with neighbors. The presence of
      neighbors affected the anatomic and metabolic characteristics of the focal males
      primarily during nesting, when males housed with rival males had a lower
      hepatosomatic index and lower activities of mitochondrial and glycolytic enzymes
      in the axial muscle than did solitary males or males housed with females.
      Cortisol levels were highly variable in nesting males and did not differ with
      social condition but were higher in males that had been quick to construct their
      nests. On the other hand, when focal males were not provided with nesting
      material, solitary males tended to have lower cortisol levels than did males
      housed with rival males. While these results do not provide a mechanism for a
      "femme fatale" effect, they indicate that nesting males decrease metabolic status
      when housed with rival "macho males."

PMID- 19758092
TI  - Jettisoning ballast or fuel? Caudal autotomy and locomotory energetics of the
      Cape dwarf gecko Lygodactylus capensis (Gekkonidae).
AB  - Many lizard species will shed their tail as a defensive response (e.g., to escape
      a putative predator or aggressive conspecific). This caudal autotomy incurs a
      number of costs as a result of loss of the tail itself, loss of resources (i.e.,
      stored in the tail or due to the cost of regeneration), and altered behavior. Few
      studies have examined the metabolic costs of caudal autotomy. A previous study
      demonstrated that geckos can move faster after tail loss as a result of reduced
      weight or friction with the substrate; however, there are no data for the effects
      of caudal autotomy on locomotory energetics. We examined the effect of tail loss
      on locomotory costs in the Cape dwarf gecko Lygodactylus capensis ( approximately
      0.9 g) using a novel method for collecting data on small lizards, a method
      previously used for arthropods. We measured CO(2) production during 5-10 min of
      exhaustive exercise (in response to stimulus) and during a 45-min recovery
      period. During exercise, we measured speed (for each meter moved) as well as
      total distance traveled. Contrary to our expectations, tailless geckos overall
      expended less effort in escape running, moving both slower and for a shorter
      distance, compared with when they were intact. Tailless geckos also exhibited
      lower excess CO(2) production (CO(2) production in excess of normal resting
      metabolic rate) during exercising. This may be due to reduced metabolically
      active tissue (tails represent 8.7% of their initial body mass). An alternative
      suggestion is that a change in energy substrate use may take place after tail
      loss. This is an intriguing finding that warrants future biochemical
      investigation before we can predict the relative costs of tail loss that lizards
      might experience under natural conditions.

PMID- 19758093
TI  - Macro- and microgeographic variation in metabolism and hormone correlates in big
      brown bats (Eptesicus fuscus).
AB  - To better understand intraspecific variation in basal metabolic rate (BMR), we
      examined environmental, physiological, and/or cellular bases for residual
      variation in BMR in big brown bats, Eptesicus fuscus. We measured BMR and plasma
      levels of thyroid hormone (T(3)) and leptin in bats captured in maternity
      colonies in eastern Massachusetts (MA; northern population) and in Alabama and
      Georgia (ALGA; southern population) to assess macrogeographic (between- or among
      population) and microgeographic (within-population) variation in those traits.
      After accounting for effects of body mass, stage of pregnancy, and within
      population variation, bats from the northern population did not differ
      significantly in BMR, T(3), or leptin values from those in the southern
      population. However, after accounting for the effects of body mass and stage of
      pregnancy, a test for differences in all traits among colonies from both
      populations was significant. For BMR, bats differed significantly among the
      northern colonies. Moreover, after removing the effects of body mass and stage of
      pregnancy, bats from the AL colony had significantly higher BMR than did bats
      from all other colonies except one in MA, and they had significantly higher T(3)
      levels but lower leptin levels than did bats from two other colonies. The
      presence of among-colony and within-population variation for these traits
      suggests that proximate (nonevolutionary) factors (e.g., microhabitat differences
      such as roost type) play an important role in shaping intraspecific variation in
      BMR and its hormone correlates.

PMID- 19758094
TI  - Risk factors for respiratory failure associated with respiratory syncytial virus
      infection in adults.
AB  - Risk factors associated with respiratory failure during respiratory syncytial
      virus (RSV) infection have not been assessed in adults. We identified RSV by
      quantitative reverse transcription polymerase chain reaction in 58 adults during
      the 2007-2008 winter. Clinical variables and respiratory secretion viral loads
      were compared in 26 outpatients and 32 inpatients. Cardiopulmonary diseases were
      more common among inpatients than outpatients (91% vs 31%, P = .0001), whereas
      mean RSV load was similar. Nasal viral load was higher in ventilated vs
      nonventilated hospitalized patients (log(10) 3.7 +/- 1.7 plaque-forming units
      (PFUs)/mL vs 2.4 +/- 1.1 PFUs/mL, P = .02), and high viral load was independently
      associated with respiratory failure.

PMID- 19758095
TI  - Effect of a point-of-use water treatment and safe water storage intervention on
      diarrhea in infants of HIV-infected mothers.
AB  - To reduce mother-to-child transmission of human immunodeficiency virus (HIV) in
      resource-poor settings, the World Health Organization recommends exclusive breast
      feeding for 6 months, followed by rapid weaning if replacement feeding is
      affordable, feasible, available, safe, and sustainable. In the Kisumu
      Breastfeeding Study (trial registration: Clinicaltrials.gov identifier
      NCT00146380), infants of HIV-infected mothers who received antiretroviral therapy
      experienced high rates of diarrhea at weaning. To address this problem, mothers
      in the Kisumu Breastfeeding Study were given safe water storage vessels, hygiene
      education, and bleach for household water treatment. We compared the incidence of
      diarrhea in infants enrolled before (cohort A) and after (cohort B)
      implementation of the intervention. Cohort B infants experienced less diarrhea
      than cohort A infants, before and after weaning (P < .001 and P = .047,
      respectively); however, during the weaning period, there were no differences in
      the frequency of diarrhea between cohorts (P = 0.89). Testing of stored water in
      cohort B homes indicated high adherence (monthly range, 80%-95%) to recommended
      chlorination practices. Among infants who were weaned early, provision of safe
      water may be insufficient to prevent weaning-associated diarrhea.

PMID- 19758096
TI  - Clean water helps but is not enough: challenges for safe replacement feeding of
      infants exposed to HIV.

PMID- 19758097
TI  - Altered nucleotide receptor expression in a murine model of cerebral malaria.
AB  - In cerebral malaria, the most severe complication of malaria, both
      neurotransmission mechanisms and energy metabolism are affected. To understand
      how metabolic changes modify neurotransmission, we examined P2 receptor
      expression in a murine model of cerebral malaria. Quantitative polymerase chain
      reaction experiments revealed that parasite deposition was greatest in the
      cerebellum, compared with other areas of the brain, suggesting a correlation
      between brain parasitemia and loss of control of movement. Infected mice showed
      modified patterns of expression of P2 receptor subtype messenger RNA (mRNA),
      depending on both the specific purinergic receptor and the cerebral region
      analyzed. Immunohistochemical studies indicated altered levels of protein
      expression by these receptors in infected brains and, in some cases, a pattern of
      expression different from that noted in control mice. These differences in both
      the amount of mRNA and the protein distribution of P2 receptors observed in the
      different brain sites in infected mice suggest an important role for P2 receptors
      in either provoking cerebral damage or conferring neuroprotection.

PMID- 19758098
TI  - Multidrug-resistant variants of HIV type 1 (HIV-1) can exist in cells as
      defective quasispecies and be rescued by superinfection with other defective HIV
      1 variants.
AB  - A tissue culture cell line infected with multidrug-resistant (MDR) human
      immunodeficiency virus type 1 (HIV-1) produced only noninfectious particles
      because of a lethal mutation in env. The defective MDR provirus was rescued by
      superinfection with either wild-type HIV-1 or a second replication-defective
      virus lethally mutated in capsid. Drug-resistance phenotyping revealed that the
      MDR viruses dominated if even single reverse-transcriptase inhibitors were
      present, reflecting linkage of the various drug resistance mutations on a single
      viral nucleic acid backbone. These results are most likely attributable to
      recombination during second rounds of infection and suggest that defective HIV-1
      variants may nonetheless constitute part of the HIV-1 reservoir.

PMID- 19758099
TI  - 3,4-Methylenedioxymethamphetamine increases susceptibility to genital herpes
      simplex virus infection in mice.
AB  - Abused by >1.2 million Americans, 3,4-methylenedioxymethamphetamine (MDMA)
      (commonly referred to as ecstasy) is popular in the dance club, rave, and circuit
      party scenes. MDMA and other similar drugs are reportedly associated with
      increased incidence of sexually transmitted infectious diseases, such as AIDS and
      genital herpes, and may have immunological effects. In the present study, we
      demonstrate that MDMA causes increased susceptibility to herpes simplex virus
      type 2 infection in mice and earlier onset of genital herpes. We also demonstrate
      that MDMA has an effect on the cytokines of the innate immune system-both
      systemically and, for the first time, in the genital tract. These data suggest
      that MDMA may play an important biological role in infection.

PMID- 19758100
TI  - Abstracts of the 16th North American Regional ISSX (International Society for the
      Study of Xenobiotics) Meeting. October 18-22, 2009. Baltimore, Maryland, USA.

PMID- 19758106
TI  - Glucose lowering and anti-atherogenic effects of incretin-based therapies: GLP-1
      analogues and DPP-4-inhibitors.
AB  - BACKGROUND: Type 2 diabetes is a chronic, progressive disease with a multi
      faceted pathophysiology. Beyond the known defects of insulin resistance and beta
      cell insufficiency, derangement of incretin hormones normally produced from the
      gut wall in response to food intake play an important role. In recent years, the
      'incretin-based' therapies (IBTs) have been developed to address hyperglycemia
      through either mimicking the action of the endogenous incretin glucagon-like
      polypeptide (GLP-1) (GLP-1 receptor agonists) or by inhibiting the activity of
      the enzyme that degrades GLP-1 (the dipeptyl peptidase-4 inhibitors). OBJECTIVE:
      We reviewed available evidence on the glucose lowering and anti-atherogenic
      effects of IBT. RESULTS: In addition to their glucose-lowering and weight-neutral
      or weight-reducing actions, IBT decrease systolic blood pressure and improve
      fasting and postprandial lipid parameters by reducing total-cholesterol, low
      density lipoprotein-cholesterol and triglycerides concentrations, and increasing
      high-density lipoprotein-cholesterol values. Reduced high-sensitivity C-reactive
      protein levels and improved endothelial dysfunction have been reported too.
      CONCLUSIONS: IBT have several beneficial effects on cardiovascular risk factors
      and, for this reason, it has been recently suggested to extend the use of these
      drugs in diabetic patients with cardiovascular complications. Yet, the long-term
      effects of IBT on subclinical or clinical atherosclerosis remain to be
      established by future studies.

PMID- 19758107
TI  - Histamine H3 and H4 receptors as novel drug targets.
AB  - The identification of histamine H3 (H3R) and H4 (H4R) receptors some years ago
      revived interest in histamine research and exposed attractive perspectives for
      the potential therapeutic exploitation of these new drug targets. While the H3R
      is mainly localised in the CNS, the H4R is primarily expressed in hematopoietic
      cells, indicating their function in neurotransmission and immunomodulation,
      respectively. Although structural similarities between H3R and H4R and species
      differences in their pharmacological profiles are causes of limitations in the
      evaluation of their biological profile, the development of selective ligands for
      these receptors facilitates the elucidation of their physiological and
      pathophysiological functions. The H3R is a recognised drug target for neuronal
      diseases, such as cognitive impairment, schizophrenia, sleep/wake disorders,
      epilepsy and neuropathic pain; a small number of selective H3R antagonists have
      already passed some clinical Phase II trials. The H4R is the newest identified
      member of the histamine receptor family. Preclinical data strongly suggest its
      potential therapeutic exploitation in allergy, inflammation, autoimmune disorders
      and possibly cancer. Considering the topicality of this area of research, this
      review focuses on the pharmacology of selected promising indications and the
      rationales for the application of H3R and H4R ligands.

PMID- 19758108
TI  - Agomelatine, a melatonin agonist with antidepressant properties.
AB  - Agomelatine (beta-methyl-6-chloromelatonin), which is structurally homologous to
      melatonin, is a potent agonist of melatonin MT1 and MT2 receptors as well as an
      antagonist of serotonin 5-HT(2C) receptors. Agomelatine appears to improve sleep
      without causing daytime sedation. It has not been found to be associated with
      sexual side effects and discontinuation symptoms. Three placebo-controlled
      trials, one of them a dose finding study and two of them pivotal trials, suggest
      that agomelatine is an antidepressant at doses of 25 - 50 mg/day. Agomelatine
      appears to be well tolerated, without sexual or cardiac adverse effects, weight
      gain or discontinuation syndromes. Animal studies suggest a possible
      neuroprotective action of agomelatine, although there are more data in favor of
      an anxiolytic effect. Substantially more research is needed to establish its role
      in the treatment of mood and circadian rhythm disorders.

PMID- 19758109
TI  - AVE8062: a new combretastatin derivative vascular disrupting agent.
AB  - Angiogenesis has an essential role in promoting and supporting tumor growth and
      it is an important therapeutic target. The tumor vascular network is the result
      of pro-angiogenic and inhibitory factors as well as of the interaction between
      endothelial cells and extracellular matrix. Different antiangiogenic therapeutics
      have been developed to improve tumor control through vascular-targeting agents
      (VTA). VTAs can be divided into two groups: antiangiogenic agents and vascular
      disrupting agents (VDAs). VTAs inhibit specific factors required to induce and
      direct the angiogenic process, with major activity against small tumor masses and
      at the tumor periphery, encompassing monoclonal antibodies and small molecules
      inhibitors of the tyrosine kinase domain of the VEGF receptor. VDAs specifically
      target and destroy well-established tumor vessels with ischemia and destruction
      of large masses with central hemorrhagic necrosis and survival of a thin
      peripheral tumor layer. VDAs can be divided into biologics, such as ligand-based,
      and small-molecule agents; this second group includes small-molecule VDAs like
      flavonoids, such as 5,6-dimethylxanthenone-4-acetic acid (DMXAA), and microtubule
      destabilizing agents. In this review we will discuss the mechanism of action, as
      well as the preclinical and clinical results, of one of the most promising
      antitubulin agents: the combretastatin A4-phosphate derivative, AVE8062A.

PMID- 19758110
TI  - Fospropofol disodium, a water-soluble prodrug of the intravenous anesthetic
      propofol (2,6-diisopropylphenol).
AB  - BACKGROUND: Today, propofol or 2,6-diisopropylphenol is the anesthetic mainly
      used for monitored anesthetic care sedation and during intravenous anesthesia.
      The formulation, a lipid macroemulsion, shows several disadvantages. Therefore,
      during the past years considerable scientific effort has been undertaken to find
      either a better formulation or a prodrug of propofol. Fospropofol is the first
      propofol prodrug that has been intensively studied in man. It has been licensed
      in 2008 by the FDA for monitored anesthetic care sedation. OBJECTIVES AND
      METHODS: This review describes first published study results of fospropofol with
      regard to its pharmacokinetics/pharmacodynamics, drug safety, tolerability and
      drug side effects. Using a Medline search all published articles and abstracts
      containing the words fospropofol or GPI 15715 were included. RESULTS AND
      CONCLUSION: As the impact of an errorness drug assay for propofol liberated from
      fospropofol is not exactly defined, no clear conclusions can be drawn from the
      first published pharmacokinetic/pharmacodynamic studies. Fospropofol was well
      tolerated in the first two clinical studies and no serious side effects were
      reported. After characterization of the true pharmacokinetic/pharmacodynamics
      profile, fospropofol, an aqueous solution, has the potential to favorably compare
      with benzodiazepines for procedural sedation and also may be used for long-term
      sedation and intravenous anesthesia.

PMID- 19758111
TI  - Reactive oxygen species and antioxidants in the pathophysiology of cardiovascular
      disease: does the actual knowledge justify a clinical approach?
AB  - There is evidence that reactive oxygen species (ROS) are related to the
      development of cardiovascular disease (CVD). Results from many studies support
      the hypothesis that ROS released from various sources or dysfunctional
      mitochondrial respiratory chain play a role in the development of atherosclerosis
      and its complications. This phenomenon is due to ROS-mediated signalling pathways
      that are involved in the modulation of several vascular mechanisms. Various
      animal models have demonstrated that ROS have a causal role in atherothrombosis
      and other vascular diseases. Oxidative stress is being proposed as the unifying
      mechanism for many CVD risk factors. In particular, ROS may be responsible for
      plaque rupture and subsequent thrombosis which lead to myocardial infarction and
      stroke. Many drugs or agents have been tested to prevent or block oxidation
      underlying atherothrombotic processes, often with discordant outcomes. We
      observed that pre-treatment with some antioxidants, such as pyrrolidine
      dithiocarbamate (PDTC) or N-acetylcysteine, as well as some vitamins with
      recognized antioxidant properties, namely ascorbic acid (vitamin C), all-trans
      Retinoic Acid (atRA) and alpha-tocopherol (vitamin E) can suppress oxidative
      stress (OS)-induced Tissue Factor (TF) expression in human coronary artery
      endothelial cells. The present review, starting from our experimental
      observations, focuses on the influence of redox balance on atherothrombotic
      processes and on the effects of antioxidant treatment. A better understanding of
      the complex regulation of cellular redox balance could facilitate the development
      of newer antioxidants aimed at specific cellular targets. Research could also
      help assess the role of combination pharmacological intervention for the
      treatment and prevention of vascular disease.

PMID- 19758112
TI  - Vascular toxicity of chemotherapeutic agents.
AB  - Cancer chemotherapy is not free of undesirable side effects. With respect to the
      cardiovascular system, cardiotoxicity is a well-described and potentially lethal
      side effect of certain chemotherapeutic agents, such as anthracyclines. However,
      in the last few years, several clinical studies have taken into account the fact
      that some non-anthracycline chemotherapy treated-patients also have a
      significantly increased risk of cardiovascular events. The exact mechanism of
      this toxicity is not known, and several possibilities, including vascular
      autonomic neuropathy and vascular damage, have been proposed. The aim of the
      present review was to collate information on the clinical and experimental
      evidence regarding vascular toxicity for each of the different groups of
      chemotherapeutic agents. The mechanisms proposed to underlie this toxicity are
      also discussed.

PMID- 19758113
TI  - Personalized medicine in psoriasis: concept and applications.
AB  - Personalized medicine is a new treatment modality where patients are the center
      of interest. Thus, one drug does not fit all; rather we look for a drug which
      fits the individual patients' disease. Treatment is moving towards molecular
      medicine driven by the growing knowledge and understanding of pharmacogenetics.
      Psoriasis is a common dermatological disease characterized by genetic
      polymorphism. The association of biomarkers and psoriasis is helpful to evaluate
      susceptibility to the disease, its severity and its progression. Additionally,
      the response to treatment will be anticipated. The growing expenses of health
      care systems worldwide are primarily due to increasing costs of chronic disease
      management. Hence, activation of preventive medicine will minimize treatment
      costs. A revolution in treatment modalities is expected to start at the level of
      pharmaceutical companies, as personalization of medicine will decrease the cost
      of clinical trials by minimizing the number of subjects required. In turn, this
      will decrease the cost of developing new medications. My vision for the future is
      that personalized medicine will mandate special physicians capable of
      understanding molecular medicine and using genetics and biomarkers for diagnosis,
      evaluation of the effect of drugs and overall prognosis. This new therapeutic
      modality will need special training.

PMID- 19758114
TI  - The rationale for comparative studies of accelerated atherosclerosis in rheumatic
      diseases.
AB  - The inflammatory pathogenesis of atherosclerosis is now well-established, owing
      to in vitro and in vivo studies and the application of high sensitivity assays
      for C-reactive protein (CRP) in the general population and specific groups at
      risk for cardiovascular disease (CVD). In view of the complexity of inflammation
      induced atherosclerosis, the rationale for comparative studies of atherogenesis
      in rheumatic diseases with diverse inflammatory pathogenesis seems obvious; they
      are human in vivo models to study inflammatory mechanisms involved in
      atherosclerosis and the impact of treatment. Factors implicated in atherogenesis
      in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), familial
      Mediterranean fever (FMF) and Behcet's disease (BD) are discussed in this review.
      Evidence suggests that enhanced atherosclerosis causes premature cardiovascular
      events in the autoimmune disease, SLE, and the "high-grade" inflammatory
      rheumatic disease, RA. Preliminary data suggest that enhanced atherogenesis may
      accompany FMF in the absence of sufficient suppression of inflammation by
      colchicine. In the setting of BD, the role of atherosclerosis in the premature
      manifestation of coronary pathology has not been confirmed; coronary vasculitis
      and aneurysms appear to constitute the basis of myocardial infarction (MI) in BD.
      A variety of established and novel risk factors are believed to influence
      enhanced atherogenesis in rheumatic diseases. Antiphospholipid antibodies are
      thought to be intimately involved in atherogenesis in SLE and to a lesser extend
      in RA. CRP may play a more universal role in all rheumatic diseases. The
      application of high resolution ultrasound of peripheral arteries and other non
      invasive techniques may allow targeted use of statins, ACE inhibitors,
      antiplatelet agents and other cardioprotective drugs in patients with rheumatic
      diseases, but this needs to be evaluated specifically in prospective studies.

PMID- 19758115
TI  - Dyslipidaemia in rheumatoid arthritis: the role of inflammation, drugs, lifestyle
      and genetic factors.
AB  - Rheumatoid arthritis (RA) associates with excess cardiovascular morbidity and
      mortality, resulting in significantly shortened lifespan. Traditional risk
      factors (e.g. dyslipidaemia and hypertension) and novel risk factors (e.g.
      systemic inflammation) contribute to the development of cardiovascular disease
      (CVD) in RA. In the general population, dyslipidaemia has been found to be
      central to the development of CVD, playing an important role in all stages of
      atherosclerotic plaque formation. In RA, lipid metabolism may be altered by
      systemic inflammation, environmental lifestyle factors, drug therapy and several
      genetic factors. This may result in changes in overall lipid levels, as well as
      modifications of lipid/lipoprotein structure and function. In this review, we
      discuss lipid abnormalities specifically in the context of RA and highlight the
      potential impact of inflammation, genetic factors, lifestyle, and anti-rheumatic
      drugs on lipid metabolism.

PMID- 19758116
TI  - The importance of early diagnosis and treatment in peripheral arterial disease:
      insights from the PARTNERS and REACH registries.
AB  - Peripheral arterial disease (PAD) is a progressive disease most often due to
      atherosclerosis and characterized by obstruction of arterial blood flow in the
      lower limbs. The defining symptom of PAD, intermittent claudication, is evident
      in only a minority of patients, leading to frequent underdiagnosis. Patients with
      PAD are more likely to suffer from polyvascular disease than patients with other
      cardiovascular conditions and have an increased risk of cardiovascular death and
      ischemic events. This review considers current PAD awareness and treatment,
      including important findings from the REduction of Atherothrombosis for Continued
      Health (REACH) and PAD Awareness, Risk and Treatment: New Resources for Survival
      (PARTNERS) registries. Information on simple diagnostic tools to aid early PAD
      detection and therapeutic options for global atherosclerosis risk factor
      management are also presented.

PMID- 19758117
TI  - Band assignment in hemoglobin porphyrin ring spectrum: using four-orbital model
      of Gouterman.
AB  - Band assignment for oxy, deoxy and methemoglobin using orbital promotion is
      crucial to understanding inter-relation of electronic transitions. Spectral
      changes may be correlated with conformational alteratiions. Conformational
      changes of hemoglobin were interpreted using four-orbital model of Gouterman. Our
      results indicated that Goutherman model can predict the predominant conformations
      of hemoglobin.

PMID- 19758118
TI  - Editorial [Hot topic: Label-free detection technologies (Guest editor: John D.
      McCarter)].

PMID- 19758119
TI  - Label-free detection of biomolecular interactions using BioLayer interferometry
      for kinetic characterization.
AB  - The analysis of biomolecular interactions is key in the drug development process.
      Label-free biosensor methods provide information on binding, kinetics,
      concentration, and the affinity of an interaction. These techniques provide real
      time monitoring of interactions between an immobilized ligand (such as a
      receptor) to an analyte in solution without the use of labels. Advances in
      biosensor design and detection using BioLayer Interferometry (BLI) provide a
      simple platform that enables label-free monitoring of biomolecular interactions
      without the use of flow cells. We review the applications of BLI in a wide
      variety of research and development environments for quantifying antibodies and
      proteins and measuring kinetics parameters.

PMID- 19758120
TI  - Mutational analysis of human heat-shock transcription factor 1 reveals a
      regulatory role for oligomerization in DNA-binding specificity.
AB  - HSF (heat-shock transcription factor) trimers bind to the HSE (heat-shock
      element) regulatory sequence of target genes and regulate gene expression. A
      typical HSE consists of at least three contiguous inverted repeats of the 5-bp
      sequence nGAAn. Yeast HSF is able to recognize discontinuous HSEs that contain
      gaps in the array of the nGAAn sequence; however, hHSF1 (human HSF1) fails to
      recognize such sites in vitro, in yeast and in HeLa cells. In the present study,
      we isolated suppressors of the temperature-sensitive growth defect of hHSF1
      expressing yeast cells. Intragenic suppressors contained amino acid substitutions
      in the DNA-binding domain of hHSF1 that enabled hHSF1 to regulate the
      transcription of genes containing discontinuous HSEs. The substitutions
      facilitated hHSF1 oligomerization, suggesting that the DNA-binding domain is
      important for this conformational change. Furthermore, other oligomerization
      prone derivatives of hHSF1 were capable of recognizing discontinuous HSEs. These
      results suggest that modulation of oligomerization is important for the HSE
      specificity of hHSF1 and imply that hHSF1 possesses the ability to bind to and
      regulate gene expression via various types of HSEs in diverse cellular processes.

PMID- 19758121
TI  - Functional insights into the role of novel type I cohesin and dockerin domains
      from Clostridium thermocellum.
AB  - Cellulosomes, synthesized by anaerobic microorganisms such as Clostridium
      thermocellum, are remarkably complex nanomachines that efficiently degrade plant
      cell wall polysaccharides. Cellulosome assembly results from the interaction of
      type I dockerin domains, present on the catalytic subunits, and the cohesin
      domains of a large non-catalytic integrating protein that acts as a molecular
      scaffold. In general, type I dockerins contain two distinct cohesin-binding
      interfaces that appear to display identical ligand specificities. Inspection of
      the C. thermocellum genome reveals 72 dockerin-containing proteins. In four of
      these proteins, Cthe_0258, Cthe_0435, Cthe_0624 and Cthe_0918, there are
      significant differences in the residues that comprise the two cohesin-binding
      sites of the type I dockerin domains. In addition, a protein of unknown function
      (Cthe_0452), containing a C-terminal cohesin highly similar to the equivalent
      domains present in C. thermocellum-integrating protein (CipA), was also
      identified. In the present study, the ligand specificities of the newly
      identified cohesin and dockerin domains are described. The results revealed that
      Cthe_0452 is located at the C. thermocellum cell surface and thus the protein was
      renamed as OlpC. The dockerins of Cthe_0258 and Cthe_0435 recognize,
      preferentially, the OlpC cohesin and thus these enzymes are believed to be
      predominantly located at the surface of the bacterium. By contrast, the dockerin
      domains of Cthe_0624 and Cthe_0918 are primarily cellulosomal since they bind
      preferentially to the cohesins of CipA. OlpC, which is a relatively abundant
      protein, may also adopt a 'warehouse' function by transiently retaining
      cellulosomal enzymes at the cell surface before they are assembled on to the
      multienzyme complex.

PMID- 19758122
TI  - Primary del 17 chronic lymphocytic leukaemia lymphocytes are hypersensitive to
      dasatinib in vitro.

PMID- 19758123
TI  - Preface. The autoimmunologist and the congresses of autoimmunity.

PMID- 19758124
TI  - Do we need autoimmune disease units in hospitals?
AB  - Autoimmune diseases are increasing worldwide, and associated morbidity,
      mortality, and health care costs are high. Biological therapies, however, have
      brought physicians an extraordinary opportunity to change natural disease
      history, although these therapies can also have high associated iatrogenic costs.
      These factors point to the necessity of having physicians that are dedicated to
      autoimmunology. The question regarding the creation of a new specialty, the
      autoimmunologist, should be addressed after an inquiry into the current practice
      in this field of medicine. This includes many classical specialties, such as
      internal medicine, rheumatology, and neurology, as well as clinical immunology.
      In clinical immunology, not counting the specialists in allergology and clinical
      immunology that mainly work only with allergies, heterogeneity is high in
      clinical practice, as the European Union of Medical Specialists documented some
      years ago. I am, at least for now, in favor of the creation of a transversal
      competency to which the different physicians working in the area could apply to
      in order to standardize the clinical practice in autoimmunology. It will be
      necessary to define a core curriculum, and in the end we shall have classical
      specialists and clinical immunologists with or without the competency of
      autoimmunology. Of utmost importance is that this new field of medicine should
      not be translated, as in the past happened with other areas, by walls between
      medical specialties. Instead it should help standardize and harmonize clinical
      practice. The time for autoimmunology is now, and, indeed, hospitals must have
      autoimmune disease units.

PMID- 19758125
TI  - Autoantibody standardization in The Netherlands.
AB  - Several initiatives have been undertaken, independent of the European
      Autoantibody Standardization Initiative (EASI), to standardize autoantibodies in
      The Netherlands. The Dutch EASI team has made an inventory of which initiatives
      on autoantibody standardization are already available and what future plans for
      autoantibody standardization exist. This inventory will subsequently be used to
      define what may be addressed by the Dutch EASI team. The Diagnostic Compass,
      initiated by the association of Dutch health insurance companies, describes
      methods and relevance of laboratory tests, including autoantibody tests.
      Recently, this initiative has been taken over by an independent publisher. There
      is also a national organization involved in developing guidelines in medicine,
      including guidelines for autoantibody testing. In addition, there is a national
      foundation for quality assessment in clinical laboratories (SKML). The quality
      assessment includes a wide array of autoantibodies. Samples are collected and
      thoroughly investigated by reference laboratories. Interpretation of results and
      advice to clinicians are part of the program. Feedback on the results of this
      proficiency testing is given in reports and during meetings to discuss trends,
      technical issues, and new developments. The last initiative that we discuss is
      the foundation Referentie Laboratorium Reuma Serologie (RELARES), which was
      founded to standardize serology in rheumatic diseases by preparing standard sera.
      Recently, RELARES has been combined with SKML. A new SKML working group,
      Standardization Autoimmune Serology, has been initiated to continue the work of
      RELARES. When comparing the already available Dutch initiatives to the
      international EASI goals, there appears to be a lack of harmonization in testing
      algorithms, and this issue is the most important topic to be addressed in the
      near future.

PMID- 19758126
TI  - Evaluation of a new ELISA assay for detection of BP230 autoantibodies in bullous
      pemphigoid.
AB  - The diagnosis of bullous pemphigoid is based on clinical observations and on the
      presence of autoantibodies directed against proteins of the dermoepidermal
      junction. Human recombinant BP180 and BP230 peptides have been used to develop
      new quantitative enzyme immunoassays (EIA) for the detection of specific
      antibodies. This study evaluated the sensitivity and specificity of a new
      immunoassay for the detection of BP230 autoantibodies and clinical correlations.
      Serum samples were tested from patients with bullous pemphigoid, other skin
      diseases, and from healthy donors. Autoantibodies anti-BP230 and anti-BP180 were
      assayed using the EIA method. Diagnostic specificity for both tests was over 98%;
      diagnostic sensitivity was 90% and 60% for anti-BP180 and anti-BP230,
      respectively. IgG anti-BP180 titers exhibited a significant correlation with
      disease activity. No patient in remission was positive for anti-BP230. In
      conclusion, anti-BP180 and anti-BP230 assays are useful in the diagnosis of
      bullous pemphigoid and provide information on disease activity.

PMID- 19758127
TI  - Accuracy of the first fully automated method for anti-cardiolipin and anti-beta2
      glycoprotein I antibody detection for the diagnosis of antiphospholipid syndrome.
AB  - In this study we evaluated the diagnostic accuracy for antiphospholipid syndrome
      (APS) of new fully automated immunoassays for anticardiolipin (aCL) and anti
      beta2 glycoprotein I (anti-beta2-GPI) auto-antibody detection (EliA-Phadia), and
      compared the results with those obtained with Orgentec and Inova ELISA methods.
      Sixty-two APS patients and 123 controls (20 syphilis, 33 Lyme disease, 30 HCV
      infection and cryoglobulinemia, 40 healthy subjects) were studied. Using the
      99(th) percentile cutoff, the sensitivity and specificity of EliA aCL IgG, aCL
      IgM, anti-beta2-GPI IgG, and anti-beta2-GPI IgM were 69.4% and 81.9%, 64.5% and
      86.7%, 64.5% and 98.8%, and 53.2% and 92.8%, respectively. Using the Sydney
      criteria cutoff (>40 GPL/MPL units), sensitivity and specificity of EliA aCL IgG
      and aCL IgM were 45.2% and 98.8%, and 35.5% and 97.5%, respectively. The best
      diagnostic efficiency was obtained combining the aCL tests (>40 GPL/MPL units)
      with the anti-beta2-GPI tests (sensitivity 85.7%, specificity 90.4%). The area
      under the ROC curves for EliA, Orgentec, and Inova methods were 0.870, 0.940, and
      0.850 for aCL IgG; 0.820, 0.820, and 0.820 for aCL IgM; 0.910, 0.960, and 0.920
      for anti-beta2-GPI IgG; 0.840, 0.840, and 0.820 for anti-beta2-GPI IgM,
      respectively. Finally, the overall agreement between EliA assays and the other
      two ELISA methods ranged from moderate (anti-beta2-GPI IgG EliA versus Orgentec:
      Cohen's k = 0.426) to good (anti-beta2-GPI IgM EliA vs. Inova: k = 0.841). In
      conclusion, newly developed EliA methods for antiphospholipid antibody detection
      perform similarly to other ELISA assays and represent a useful tool for APS
      laboratory diagnosis in daily practice.

PMID- 19758128
TI  - New developments in serodiagnosis of childhood celiac disease: assay of
      antibodies against deamidated gliadin.
AB  - Antibodies to deamidated gliadin present a new tool in the diagnosis of celiac
      disease (CD). In children, the ELISA for the determination of IgG antibodies to
      (deamidated) gliadin-analogous fusion peptides (GAF3X) has a superior performance
      compared to the ELISA for the determination of antibodies against native gliadin
      and is comparable to assays for IgA antibodies against tissue transglutaminase
      (IgA-anti-tTG). The combined investigation of IgG antibodies to GAF3X (IgG-anti
      GAF3X) and IgA-anti-tTG significantly increases the fraction of children
      definitely identified as either CD or non-CD patients. The new IgG-anti-GAF3X
      ELISA was also able to detect CD in three cases of IgA deficiency and in two
      cases of latent CD and was also useful in the diagnosis of children younger than
      2 years of age.

PMID- 19758129
TI  - Celiac G+ antibody assay for the detection of autoantibodies in celiac disease.
AB  - Celiac disease (CD) affects approximately 1% of the population and may present
      with varied symptomatic as well as asymptomatic clinical manifestations. Simple
      methods of detecting CD such as serum antibody tests have helped in the early
      identification of the disease thus preventing serious complications of the
      disorder. Our objective is to develop specific and sensitive immunoassays that
      are reliable in the detection of CD. To this end, immunoassays were developed for
      the detection of IgG and IgA antibodies to gliadin using synthetic peptides. Over
      200 serum samples were included in the study from individuals with CD submitted
      for endomysial (EMA) and tissue transglutaminase (tTG) antibody tests as well as
      from disease controls and healthy normals. To examine the reliability of the
      Celiac G+ antibody test in comparison with EMA, a test with higher sensitivity
      and specificity, samples with low and high EMA titers were included in the study.
      Comparative evaluations of the Celiac G+ antibody assay were made with EMA and
      another commercially available gliadin peptide assay along with tTG antibody
      assays. The data show that as the EMA levels increased the sensitivity of
      detection of antibodies to synthetic peptides on both systems increased, reaching
      100% at EMA titers greater than 160. The diagnostic performance of the newly
      developed Celiac G+ synthetic gliadin peptide assay is significantly superior in
      comparison with another available gliadin peptide immunoassay. Overall, the
      diagnostic performance of the Celiac G+ assay for IgA and IgG reached a
      sensitivity of 80% and 90% respectively in comparison with EMA. Similar
      comparison of the EMA positivity to the other available synthetic peptide
      immunoassay yielded sensitivities of 59% (IgA) and 75% (IgG). The specificity of
      the Celiac G+ antibody assay for IgA and IgG was 90-95% as compared to the other
      similar assay with specificity of 88-90%. In conclusion, the performance of the
      recently developed Celiac G+ ELISA is superior in both its sensitivity and
      specificity in comparison with other available synthetic gliadin peptide
      immunoassays. Furthermore, the IgG Celiac G+ antibody test and IgA tTG antibody
      test used in combination is an excellent screening algorithm for suspected cases
      of celiac disease.

PMID- 19758130
TI  - High-sensitivity detection of autoantibodies against proteinase-3 by a novel
      third-generation enzyme-linked immunosorbent assay.
AB  - The aim of this study was to evaluate a novel third-generation enzyme-linked
      immunosorbent assay (ELISA) for the high-sensitivity detection of autoantibodies
      to proteinase-3 (PR3) in patients with Wegener's granulomatosis (WG). First- and
      second-generation ELISA for the detection of antineutrophil cytoplasmic
      antibodies (ANCA) frequently demonstrate insufficient sensitivity due to
      inadequate presentation of autoantigenic epitopes. Human PR3 was immobilized on
      the solid phase of ELISA plates by anchoring technique. Anti-PR3 reactivity was
      measured in 34 C-ANCA positive patients with WG, 11 MPO-ANCA-positive patients
      with other autoimmune vasculitides, 65 patients with systemic lupus erythematosus
      (SLE), and 137 healthy blood donors. Thirty-three of 34 patients with WG (97.1%)
      showed positive anti-PR3 IgG antibody reactivity. None of 11 MPO-ANCA positive
      vasculitis patients, none of 137 blood donors, and 3 of 65 SLE patients expressed
      elevated IgG reactivity to PR3 (specificity: 98.4%). Comparison with another
      third-generation ELISA did not reveal different qualitative results. However,
      there was no significant correlation between quantitative results of both assays.
      Receiver operating characteristic (ROC) curve analysis revealed a significantly
      better assay performance compared with first (direct)- and second (capture)
      generation assays (P = 0.011 and P = 0.001, respectively). Third-generation
      (anchor) anti-PR3 ELISA exhibit significantly higher sensitivity than previous
      generation assays. Anchoring of PR3 renders the granulocyte protein more
      autoantigenic compared with direct or capture immobilization.

PMID- 19758131
TI  - Anti-C1q autoantibodies in lupus nephritis.
AB  - Anti-C1q antibodies are found in a variety of diseases, in addition to systemic
      lupus erythematosus (SLE), and in 3-5% of normal individuals. In particular, anti
      C1q antibodies are detected at a high titer in 100% of patients with
      hypocomplementemic urticarial vasculitis and in 30-48% of SLE patients. Their
      titer correlates with active renal disease with a sensitivity of 44-100% and a
      specificity of 70-92%. An increase in anti-C1q antibody titer has been suggested
      to be able to predict renal flares in lupus nephritis so that monitoring anti-C1q
      might be valuable for the clinical management of SLE patients as a noninvasive
      biological marker. Recently our group studied 228 patients affected by lupus
      nephritis and found that the association of anti-C1q, C3, and C4, in a
      multivariate analysis, provided the best prediction of renal flares, particularly
      in patients with focal and diffuse proliferative lupus nephritis and in the
      absence of antiphospholipid antibodies.

PMID- 19758132
TI  - Seronegative autoimmune diseases.
AB  - A close relationship exists between autoimmunity and autoantibodies; despite
      this, some patients are persistently negative for disease-specific
      autoantibodies. These conditions have been defined as seronegative autoimmune
      diseases. Although the prevalence of seronegative autoimmune diseases is low,
      they may represent a practical problem because they are often difficult cases.
      There are also situations in which autoantibodies are positive in healthy
      subjects. In particular, three different conditions can be described: latent
      autoimmunity, preclinical autoimmunity, and postclinical autoimmunity. Here, we
      analyze briefly the meaning of autoantibody negativity in the seronegative
      autoimmune diseases, focusing in particular on the specificities associated with
      systemic lupus erythematosus, antiphospholipid syndrome, and rheumatoid
      arthritis.

PMID- 19758133
TI  - Correlation between clinical activity and serological markers in a wide cohort of
      patients with systemic lupus erythematosus: an eight-year prospective study.
AB  - Titers of serum anti-double-stranded DNA antibodies (anti-dsDNA Abs) and C3 and
      C4 are used for monitoring systematic lupus erythematosus (SLE) patients. Here,
      we assessed the relationship between the clinical activity index (SLEDAI) and
      serum titers of anti-dsDNA Abs, C3, and C4 in an 8-year prospective study
      conducted in 194 SLE patients. The association of anti-dsDNA Abs and complement
      with M-SLEDAI was significant but low. Ninety-eight of the 194 patients were
      selected because they were followed for at least 5 years. We observed four types
      of clinical-serological patterns: parallelism between serum and clinical activity
      (n = 24), clinical quiescence with partial serum activity (n = 30), clinical
      quiescence but serologically fully active (n = 18), and clinical activity but
      serologically quiescent (n = 21). The serological markers evaluated are of
      limited utility in the monitoring of SLE patients and their use must be
      individualized.

PMID- 19758134
TI  - Circulating cardiac troponin-I autoantibodies in human plasma and serum.
AB  - We identified IgG reactive with human cardiac troponin-I (cTnI) in plasma and
      serum samples (N = 1930) from normal blood donors, and in sample cohorts
      characterized on the basis of clinical biomarkers associated with cardiac,
      infectious, and autoimmune diseases. cTnI and brain natriuretic peptide were the
      biomarkers chosen to reflect myocyte damage or left ventricular dysfunction,
      respectively. The infectious disease cohorts were serologically positive for
      antibodies to hepatitis B (natural infection), hepatitis C virus, and Chagas
      (i.e., T.cruzi). The autoimmune cohorts were represented by samples from
      diagnosed systemic lupus erythematosus (biomarker: dsDNA) and rheumatoid
      arthritis (biomarker: rheumatoid factor) subjects. The prevalence of IgG
      autoantibodies reactive with cTnI was high in the normal donor cohort (95/750,
      12.7%). The prevalence in the other sample cohorts was not significantly
      different from that in the normal blood donors, with the exception of a slight
      increase in the rheumatoid factor cohort (28/137, 20.4%). The presence of anti
      cTnI IgG in highly reactive samples was confirmed by inhibition with the antigen
      and further by screening with a library of peptides derived from the human cTnI
      amino acid sequence. Our data suggest that these autoantibodies are polyspecific,
      encompassing epitopes across the entire cTnI sequence, including the cardiac
      specific amino terminal region.

PMID- 19758135
TI  - Choroid plexus connexin 43 expression and gap junction flexibility are associated
      with clinical features of acute EAE.
AB  - Experimental autoimmune encephalomyelitis (EAE) induced by ventricular injection
      of antimyelin oligodendrocyte antibodies in DA rats showed severe clinical signs
      4 to 5 days after injection. Immunocytochemically, connexin 43 (Cx43) expression
      increased in the choroid plexus and in the subventricular and subgranular zones
      of the hippocampus during the development of acute EAE, and decreased after the
      beginning of the remission phase of the disease. Quantitative computing analysis
      showed a significantly increased Cx43 expression in the choroid plexus at the
      peak of the disease. Plaque-pattern expression of the Cx43 in the choroid plexus
      (CP) of acute EAE correlated with the increased docking and coupling of the Cx43
      hemichannels revealed by atomic force microscopy (AFM). The inner diameter of the
      gap junction (GJ) channels decreased in the CP of acute EAE, measured by AFM.
      Cell structure conformational changes showed influences the channels' flexibility
      in acute EAE.

PMID- 19758136
TI  - Autoantigens identified by screening a human heart cDNA library with acute
      rheumatic fever sera.
AB  - Acute rheumatic fever (ARF) is an autoimmune sequela of group A streptococcal
      infection mostly affecting school-aged children. Recurrent episodes of ARF can
      result in the development of rheumatic heart disease (RHD). One in 40 indigenous
      Australians in the Northern Territory is affected by RHD. This disease mostly
      impacts young people; 45% of those who require heart valve surgery in Australia
      due to RHD are younger than 25 years old. ARF is characterized by autoimmune
      attack of the heart; therefore, the presence of the autoantibodies involved could
      potentially be used to diagnose ARF. To this end, a human heart cDNA library was
      screened with serum from a patient with ARF, and 12 autoreactive human heart
      antigens were identified. They include five different IgG heavy chains and a
      range of tissue-specific cell-signaling proteins, species of which have been
      implicated in other autoimmune diseases. Preliminary ELISA results show that ARF
      patients have significantly higher levels of antibodies recognizing the cardiac
      autoantigens than controls. These antigens are promising candidates for the
      development of a serological assay for the diagnosis of ARF. The nature of the
      proteins identified has exciting implications for future research into the
      pathogenesis of ARF.

PMID- 19758137
TI  - Optimization of high-throughput autoantibody profiling for the discovery of novel
      antigenic targets in rheumatoid arthritis.
AB  - A major focus in rheumatoid arthritis (RA) research is the identification of the
      antigens that are targeted by the joint-directed autoimmune response. B cells and
      associated autoantibodies have been studied in RA to identify the antigenic
      targets and to discover RA-associated autoantibodies which can be used as disease
      markers. This research indicated the heterogeneity of the autoantibody profile in
      RA and the large overlap in antibody specificities with other rheumatic diseases
      pointing toward the need for multiplexing to identify an RA-associated
      autoantibody profile. The discovery of antibodies directed against cyclic
      citrullinated peptides (ACPA) has led to great advances in RA research. This
      finding generated novel autoantigen suspects in ACPA-positive RA patients, which
      comprise approximately two-thirds of the entire RA population, namely
      citrullinated peptides and/or proteins. One-third of the RA patients, however, do
      not show ACPA, and it is now postulated that ACPA-positive and ACPA-negative RA
      are two different disease entities with different genetic associations,
      pathogenesis, and etiology. The analysis of autoantibodies in ACPA-negative RA
      could provide insight into the identity of antigenic targets and markers for this
      disease subtype. We report here the optimization of an unbiased, high-throughput
      autoantibody profiling procedure based on cDNA phage display for the detection of
      novel autoantibody targets in ACPA-negative RA. The discovery of specific
      autoantibodies in this RA subtype could lead to great advances in the diagnosis
      of these patients and could provide clues regarding disease etiology and
      pathogenesis of ACPA-negative RA.

PMID- 19758138
TI  - White blood cell count abnormalities and infections in one-year follow-up of 124
      patients with SLE.
AB  - The purpose of our study was to evaluate the frequency of leukocyte count
      abnormalities in a large cohort of SLE patients and its association with
      infection. To make this evaluation, we studied consecutive patients with SLE
      diagnosis and prospectively followed them in the Coimbra Lupus Cohort. Data about
      white blood cell count abnormalities and infection during one-year follow-up were
      obtained. The presence of leukopenia, lymphopenia, and neutropenia was registered
      for one-year period. Infections were classified as severe or mild. We found that
      of the 124 patients who were included (91.1% female, mean age 41.2, mean disease
      duration 11.1), mild infections occurred in 43.5%, and severe in 3.2% of the
      patients. Twelve percent, 41.1%, and 4.8% of the patients had persistent
      leukopenia, lymphopenia, and neutropenia, respectively. Fourteen percent received
      a pneumococcal vaccination. Patients with neutropenia had a significantly higher
      number of infections (P = 0.033). Thus, our study showed that neutropenia was
      associated with an increased risk of infection during this one-year follow-up.
      Infections were frequent, but most of them were mild.

PMID- 19758139
TI  - Clinical significance of complement deficiencies.
AB  - The complement system is composed of more than 30 serum and membrane-bound
      proteins, all of which are needed for normal function of complement in innate and
      adaptive immunity. Historically, deficiencies within the complement system have
      been suspected when young children have had recurrent and difficult-to-control
      infections. As our understanding of the complement system has increased, many
      other diseases have been attributed to deficiencies within the complement system.
      Generally, complement deficiencies within the classical pathway lead to increased
      susceptibility to encapsulated bacterial infections as well as a syndrome
      resembling systemic lupus erythematosus. Complement deficiencies within the
      mannose-binding lectin pathway generally lead to increased bacterial infections,
      and deficiencies within the alternative pathway usually lead to an increased
      frequency of Neisseria infections. However, factor H deficiency can lead to
      membranoproliferative glomerulonephritis and hemolytic uremic syndrome. Finally,
      deficiencies within the terminal complement pathway lead to an increased
      incidence of Neisseria infections. Two other notable complement-associated
      deficiencies are complement receptor 3 and 4 deficiency, which result from a
      deficiency of CD18, a disease known as leukocyte adhesion deficiency type 1, and
      CD59 deficiency, which causes paroxysmal nocturnal hemoglobinuria. Most inherited
      deficiencies of the complement system are autosomal recessive, but properidin
      deficiency is X-linked recessive, deficiency of C1 inhibitor is autosomal
      dominant, and mannose-binding lectin and factor I deficiencies are autosomal co
      dominant. The diversity of clinical manifestations of complement deficiencies
      reflects the complexity of the complement system.

PMID- 19758140
TI  - An italian multicenter study for application of a diagnostic algorithm in
      autoantibody testing.
AB  - The presence in the serum of specific autoantibodies, such as antinuclear
      antibodies (ANA), anti-double-stranded DNA (anti-dsDNA), and antiextractable
      nuclear antigens (anti-ENA), is one of the diagnostic criteria for autoimmune
      rheumatic disease, and the requests for these tests in the last few years have
      grown remarkably. A guideline for reducing clinically inappropriate requests in
      autoantibody testing (ANA, anti-dsDNA, anti-ENA) has been applied in the Parma
      Hospital since 2007. The results for the period January-December 2007 were
      compared to those of the previous period January-December 2006, and a significant
      reduction in the number of anti-dsDNA (23.9%) and anti-ENA (20.7%) was found. The
      aim of this study was to assess the applicability of a similar guideline in a
      wide area (Parma, Modena, Piacenza, Reggio-Emilia) with reference to the
      diagnosis of autoimmune rheumatic disease. This project, supported by a regional
      grant for innovative research projects, was started in January 2008 and consists
      of three different steps: (1) a study group of clinicians and laboratory
      physicians to evaluate the diagnostic criteria, the analytical procedures, and
      the number of tests performed in different hospitals; (2) developing common
      guidelines for autoantibody testing that takes into account the different
      clinical needs with the aim of improving efficiency and clinical effectiveness of
      diagnosis and monitoring; and (3) assessing compliance with the guidelines in the
      different hospitals that are evaluating the second-level test (anti-dsDNA, anti
      ENA) decrease. We think that the validation of guidelines for the laboratory
      diagnosis of autoimmune rheumatic disease can represent a tool for improving
      patients' outcomes and economic efficiency.

PMID- 19758141
TI  - Antibodies to neurofilaments.
AB  - Immune responses to neuronal proteins are a frequent occurrence in
      neurodegenerative diseases. This study determines the occurrence of
      autoantibodies to the three neurofilament subunits in phosphorylated and
      dephosphorylated forms and relates these measures to age, human leukocyte antigen
      (HLA), and severity of disease in Down syndrome (DS). IgG-type antibodies to
      three neurofilament (NF) subunits, NF-L, NF-M, and NF-H, in both phosphorylated
      and dephosphorylated forms were tested by immunoblot in 128 patients with DS and
      compared to antibody levels in 94 normal controls. DS was revealed by karyotype
      analysis. Antibodies to dephospho-NF-M, NF-M, and NF-L were more common in DS
      samples than in controls. Total pools of DS and control samples had similar
      frequency of antibodies to NF-H, but there was a higher prevalence of antibodies
      against NF-H in DS patients with moderate or mild disability (43.0%) compared
      with those having serious disability (14.3%). No NF-H antibody was seen among
      young children (age 14 years or younger) of the latter group. The HLA-DR15 allele
      was negatively correlated with antibodies against NF-H. The high prevalence of
      antibodies to neurofilament proteins and the differences between DS and control
      samples may reflect the cross-talk between neural and immune systems that could
      have an important role in defending neural structures from neurodegenerative
      processes. In children with DS the presence of antibodies to NF-H might reflect a
      more favorable prognosis.

PMID- 19758142
TI  - Possible involvement of chemokine-induced platelet activation in thrombophilic
      diathesis of antiphospholipid syndrome.
AB  - Among the heterogeneous antiphospholipid antibodies, many studies suggest that
      those directed to beta2-glycoprotein I (beta2GPI) are the major pathogenic
      antibodies in antiphospholipid syndrome (APS). They have been shown to activate
      the coagulation pathway via several mechanisms, activate platelets via thrombin
      formation, and suppress fibrinolysis. Additionally, we propose another possible
      mechanism that involves certain chemokines and results in platelet activation.
      This hypothesis is based on the observations that anti-beta2GPI antibodies
      stimulated monocytes to secrete inflammatory cytokines such as IL-1beta and TNF
      alpha, which in turn stimulated vascular endothelial cells to express chemokines
      such as CX3CL1 and CCL5. CX3CL1 increased the ability of normal platelets to
      adhere to collagen at a high shear rate, while CCL5 induced platelet aggregation.
      Expression of tissue factor, IL-1beta, and TNF-alpha by monocytes stimulated with
      anti-beta2GPI antibodies, as well as CX3CL1 and CCL5 by vascular endothelial
      cells stimulated with IL-1beta or TNF-alpha were all suppressed by the NF-kappaB
      specific inhibitor DHMEQ. These results suggest that the NF-kappaB pathway may be
      a potential therapeutic target relating to both the coagulation pathway and
      platelet activity.

PMID- 19758143
TI  - Prevalence of anticardiolipin antibodies in patient cohorts with distinct
      clinical manifestations of the antiphospholipid syndrome.
AB  - Clinical manifestations of antiphospholipid syndrome (APS) vary from venous and
      arterial thrombosis to pregnancy loss and pre-eclampsia (PEC). Our aims were to
      establish the prevalence of anticardiolipin antibodies (aCLA) in patients with
      clinical features of APS and to compare the reference ELISA method with the novel
      automated EliA aCLA assay. Serum samples from 1278 patients with either deep
      venous thrombosis (DVT), young stroke (YS), PEC, or multiple sclerosis (MS) were
      included. The latter cohort was included because initial presentation of APS
      might resemble MS. Using the internationally accepted cutoff level of 40 MPL/GPL
      [IgM antiphospholipid units/mL (MPL)/IgG antiphospholipid units/mL (GPL)], 0.7%
      and 0.5% of the samples were positive for IgM and IgG aCLA by ELISA,
      respectively. Using the cutoff level recommended by the manufacturer (15
      MPL/GPL), the prevalence was 2.7% and 2.8%, respectively. The prevalence by EliA
      was 2.0% and 0.5% for IgM and IgG aCLA, respectively (40 MPL/GPL cutoff).
      However, with a low cutoff level, the prevalence of IgM aCLA, but not IgG aCLA,
      was higher in the DVT (14.3%), YS (14.6%), and PEC (17.7%) cohorts but not the MS
      cohort. The prevalence of aCLA was too low for reliable determination of
      concordance between assays. In patients with DVT, CVA, PEC, and MS, the
      prevalence of aCLA is low, in particular when internationally accepted cutoff
      values are applied. Our finding questions the efficacy of aCLA testing.
      Therefore, there might be either a need for defining specific clinical criteria
      to obtain a better rational for aCLA testing or aCLA testing should be excluded
      from the classification criteria.

PMID- 19758144
TI  - Characterization of antibodies directed against the immunoglobulin light kappa
      chain variable chain region (VK) of hepatitis C virus-related type-II mixed
      cryoglobulinemia and B-cell proliferations.
AB  - Autoimmune type-II cryoglobulinemia (II-MC) is sustained by hepatitis C virus
      (HCV) infection and B-cell (oligo)clones. This is the reason why the disease may
      be considered an "indolent B-cell lymphoma (NHL)." B clones show a restricted use
      of immunoglobulin variable genes (BCR), in particular in the use of the variable
      kappa (VK)3-20/15 light chain, and show a homology between their BCR functional
      regions and those of autoimmune rheumatoid factors. We underlined the BCR unique
      repertoire with frequent rheumatoid factor activity also observed in other
      autoimmune disorders associated with NHL. The immunoglobulin idiotype is a clonal
      B-cell marker and an ideal target for immunotherapy. Five monoclonal antibodies
      were produced in our laboratory toward the VK3-20 of a subject with HCV infection
      and a II-MC-associated NHL. Epitope determination was performed using the epitope
      excision approach. Monoclonal antibody reactivity was tested in vitro in ELISA,
      Western blot, and cytofluorimetry. Data confirmed that a panel of antibodies,
      reactive against shared idiotypes, can be produced from patients with HCV
      associated B-cell lymphoproliferative diseases, thus obviating the need to
      produce an anti-idiotype antibody for each patient.

PMID- 19758145
TI  - DNA-bound lactoferrin is the major target for antineutrophil perinuclear
      cytoplasmic antibodies in ulcerative colitis.
AB  - Lactoferrin has repeatedly been proposed to be a target for antineutrophil
      perinuclear cytoplasmic antibodies (P-ANCA), which are present in 67% of
      ulcerative colitis (UC) cases. However, this high prevalence has not been
      achieved with either Western blots or monospecific ELISA on the basis of purified
      lactoferrin bound to the solid phase. We reevaluated autoantibodies against
      lactoferrin by indirect immunofluorescence (IIF), using a lactoferrin-tuned
      granulocyte substrate. Slides with ethanol-fixed human granulocytes were stripped
      of their P-ANCA targets by high-salt treatment and then reconstituted with human
      lactoferrin (LFR granulocytes). The slides were then subjected to IIF with a
      panel of sera (39 UC, 10 antimyeloperoxidase-positive vasculitis, 50 healthy
      blood donors). The human sera were also analyzed with antilactoferrin ELISA. In
      28 of 39 (71.8%) sera from UC patients, antibodies could be determined that bound
      exclusively to LFR granulocytes. Nuclease-treated cells failed to show this
      reactivity. ELISA detected antilactoferrin antibodies in only two UC sera.
      Lactoferrin is a major P-ANCA target in UC but requires DNA to present the
      epitopes relevant for the reaction with the autoantibodies. Antigen-stripped and
      lactoferrin-reconstituted granulocytes can be used in IIF to diagnose
      antilactoferrin antibodies in UC more reliably than with existing ELISA systems.

PMID- 19758146
TI  - Autoantibody detection using indirect immunofluorescence on HEp-2 cells.
AB  - The detection of autoantibodies is an important element in the diagnosis and
      monitoring of disease progression in patients with autoimmune diseases. In
      laboratory diagnostic tests for connective tissue and autoimmune liver diseases,
      indirect immunofluorescence on HEp-2 cells plays a central role in a multistage
      diagnostic process. Despite the high quality of diagnostics, findings at
      different laboratories can differ considerably due to a lack of standardization,
      as well as subjective factors. The present paper formulates recommendations for
      the standardized processing and interpretation of the HEp-2 cell test for the
      detection of non-organ-specific (especially antinuclear) antibodies. It provides
      requirements regarding the diagnostic tests used, instructions for laboratory
      procedure and evaluation, and recommendations for interpretation. For an optimal
      laboratory diagnostic process, it is useful to have an informative, tentative
      clinical diagnosis and an experienced laboratory diagnostician. In addition, the
      following key elements are recommended: initial screening using indirect
      immunofluorescence on carefully chosen HEp-2 cells beginning with a serum
      dilution of 1:80 and evaluation under a microscope with powerful illumination;
      results from a titer of 1:160 upwards being considered positive; internal
      laboratory quality control; and standardized interpretation. The aim is to
      improve diagnostic tests and care of patients with autoimmune diseases as a
      central concern of the European Autoimmunity Standardization Initiative (EASI).

PMID- 19758147
TI  - Autoantibody screen in inflammatory myopathies high prevalence of antibodies to
      gliadin.
AB  - BACKGROUND: Inflammatory myopathies (IM) are associated with autoimmune diseases.
      AIM: To evaluate the titers of auto-antibodies specific to various autoimmune
      diseases in patients with IM compared with controls. METHODS: Sera from 99 IM
      patients and 100 healthy controls were tested for autoantibodies for vasculitis
      (myeloperoxidase, PR3, and glomerular basement membrane) and autoimmune
      gastrointestinal diseases (IgA and IgG antigliadin, antitissue transglutaminase,
      and Saccharomyces cerevisiae) utilizing the BioPlex 2200 Multiplexed Immunoassay
      method (Biorad). RESULTS: Antigliadin IgA levels were significantly elevated in
      IM patients compared with controls (0.37 units +/- 0.44 vs. 0.24 units +/- 0.15,
      P = 0.017). Antitissue transglutaminase IgA was marginally increased in IM
      patients versus controls (0.36 units +/- 1.12 vs. 0.2 units +/- 0.0, P = 0.08).
      CONCLUSIONS: Antibodies to gliadin and tissue transglutaminase characteristic for
      celiac disease were elevated in patients with IM compared with controls. This may
      indicate a higher prevalence of gluten sensitivity or celiac disease in IM.

PMID- 19758148
TI  - High sensitive detection of double-stranded DNA autoantibodies by a modified
      Crithidia luciliae immunofluorescence test.
AB  - Anti-double-stranded (ds)DNA antibodies are serological markers of systemic lupus
      erythematosus (SLE). Of all anti-dsDNA antibody detection methods, the Crithidia
      luciliae immunofluorescence test (CLIFT) is thought to have the highest
      specificity for SLE. However, the clinical application is hampered by the low
      diagnostic sensitivity. A CLIFT with modified assay buffer (mCLIFT) was developed
      and compared with conventional CLIFT, using sera from 110 patients with SLE, 89
      anti-dsDNA ELISA-positive patients with other diseases (non-SLE group A), 157 non
      SLE patients with undetectable anti-dsDNA antibodies by ELISA (non-SLE group B),
      77 disease controls (non-SLE group C), and 50 healthy blood donors. Out of the
      110 anti-dsDNA antibody ELISA-positive SLE patients, 84 (76.4%) demonstrated a
      positive kinetoplast staining, using the mCLIFT, compared to only 42.3%, using
      the conventional CLIFT. The diagnostic specificity of mCLIFT was 100% with
      healthy blood donors and 98.1% with the non-SLE group C (anti-nuclear antibodies
      negative; no signs or symptoms of an autoimmune disease) included. In the non-SLE
      groups A and B with various other autoimmune diseases or symptoms of a possible
      autoimmune disease, positive mCLIFT results were obtained in 33.7% and 3.2%,
      respectively. In conclusion, by modification of the assay buffer, a significant
      increase in sensitivity of the CLIFT could be observed while retaining the high
      specificity for SLE. Further investigation is required to check whether the CLIFT
      positive non-SLE patients develop SLE and whether anti-dsDNA antibodies detected
      by the mCLIFT represent a pathogenetic and diagnostic subgroup of autoantibodies
      that may improve the early diagnosis of SLE or SLE-overlap syndromes.

PMID- 19758149
TI  - The incidence of celiac disease antibodies in plasma specimens with low
      hemoglobin levels.
AB  - Antibodies to gliadin and tissue transglutaminase (TTG) are associated with
      celiac disease. Celiac patients often present with low hemoglobin levels;
      however, the incidence of celiac disease in patients with low hemoglobin levels
      is unknown. We investigated the incidence of celiac disease-associated antibodies
      in plasma obtained from individuals with low and normal hemoglobin levels. Our
      objective was to determine if antigliadin and anti-TTG antibodies are more
      prevalent in individuals with low hemoglobin levels than in control subjects with
      normal hemoglobin levels. Following IRB approval, we obtained 86 plasma specimens
      with hemoglobin levels less than or equal to 10 g/dL and 88 plasma specimens from
      individuals with hemoglobin levels greater than or equal to 13 g/dL. IgA and IgG
      antibodies to gliadin and TTG were determined by ELISA assays provided by BioRad,
      Inc. IgG antigliadin Ab was present in 6 out of 86 low hemoglobin specimens and
      in two of the normal hemoglobin specimens. The IgA antigliadin ELISA assay was
      positive in 19 out of 86 low hemoglobin specimens and in 21 out of 88 normal
      hemoglobin specimens. IgA anti-TTG was detected in 9 out of 86 low hemoglobin
      specimens and in 3 out of 88 normal hemoglobin specimens. IgG anti-TTG was not
      present in any of the specimens. IgA antibodies to TTG were more prevalent in
      individuals with low hemoglobin levels. The incidence of IgG anti-TTG and IgG and
      IgA antibodies to gliadin was not related to plasma hemoglobin levels in our
      sample.

PMID- 19758150
TI  - Development of recombinant human IgA for anticardiolipin antibodies assay
      standardization.
AB  - Controls and calibrators in autoimmune assays are typically developed from
      patient sera. However, the use of sera is accompanied by a number of
      disadvantages, such as lack of monospecificity, lack of assay comparability, and
      supply limitations. Ideally, the control reagent would be an antigen-specific
      human monoclonal antibody preparation that is defined and pure, easy to produce
      without any supply limitations, and of defined isotype (IgG, IgM, or IgA). The
      generation of antigen-specific human monoclonal antibodies has been complicated,
      but recent advances in development of fully human antibodies by means of in vitro
      antibody gene library selection has opened a way for the isolation of human
      antibodies to virtually any antigen, including self-antigens. Such antibodies can
      be converted to any isotype by gene cloning. Here we developed a set of human
      monoclonal IgA antibodies specific for the cardiolipin-beta2-glycoprotein 1
      complex, using the HuCAL technology. We evaluated the IgA variants of those
      antibodies for their use as standards in IgA anticardiolipin antibody assays and
      compared these reagents with serum controls. Such recombinant antibodies may
      ultimately replace patient sera as assay control and calibration reagents.

PMID- 19758151
TI  - Pneumatosis intestinalis presenting in autoimmune diseases: a report of three
      patients.
AB  - Pneumatosis intestinalis (PI) is an uncommon condition characterized by the
      presence of gas within the wall of the gastrointestinal tract. PI is a physical
      or imaging finding that is the result of an underlying pathological process or a
      disease. This finding may present in diverse conditions, such as obstructive
      pulmonary disease and intestinal disease, including obstruction, inflammation, or
      ischemia. PI has also been reported in different autoimmune conditions,
      especially in systemic sclerosis and rarely with systemic lupus erythematosus. In
      this report we present PI occurring in three patients with different autoimmune
      conditions and review the literature.

PMID- 19758152
TI  - Autoimmune bullous dermatoses: a review.
AB  - Bullous dermatoses are a variety of autoimmune skin diseases that are
      characterized by the presence of bullae or blisters. Most of these diseases are
      associated with substantial morbidity, and a few may result in death. Although
      most general approaches to the treatment and diagnosis of these entities are
      similar, the diagnosis of the specific disease is important, because the most
      appropriate dosage and timing of some commonly used medications vary
      considerably. The review covers the management of main autoimmune bullous
      dermatoses, including bullous pemphigoid and pemphigus vulgaris, linear IgA
      dermatosis, dermatitis herpetiformis, and bullous systemic lupus erythematosus.

PMID- 19758153
TI  - Autoimmune thyroid disease and autoimmune rheumatic disorders: a two-sided
      analysis.
AB  - Chronic autoimmune thyroiditis (ATD) frequently overlaps with autoimmune
      rheumatic diseases. The aim of this study was to evaluate the prevalence of
      various non-organ-specific autoantibodies in patients with ATD, as well as the
      presence of ATD in patients with systemic lupus erythematosus (SLE) and
      rheumatoid arthritis (RA). SUBJECTS AND METHODS: Group 1 comprised 80 patients
      with ATD, and group 2 contained 80 patients with SLE or RA. A control group
      consisted of 34 healthy subjects. Group 1 was examined for the presence of non
      organ-specific autoantibodies. Serum fT3, fT4, TSH, and antibodies against
      thyroglobulin, thyroperoxidase, as well as ultrasound of thyroid gland, were
      determined in group 2. RESULTS: Patients with ATD had a significantly higher
      prevalence of antinuclear antibodies (ANA) than control subjects (45% vs. 14.7%,
      P < 0.001). There were no significant differences in the prevalence of other
      antibodies between the groups. ANA-positive patients were younger than ANA
      negative ones and had significantly higher anti-TG values (P < 0.05). The
      prevalence of ATD in group 2 was significantly higher than in the control
      subjects (24% vs. 8%, P < 0.05). No significant differences in the prevalence of
      ATD were detected between SLE and RA. CONCLUSION: The authors conclude that ANA
      is the most frequent non-organ-specific antibody associated with ATD, while the
      other antibodies occur rarely. The prevalence of ATD in SLE and RA patients was
      24%. These results indicate that it is clinically important to screen patients
      with SLE and RA for the coexistence of thyroid autoimmune disease.

PMID- 19758154
TI  - Cognitive functioning in Behcet's disease.
AB  - The impact of Behcet's disease on higher cognitive functions is still poorly
      understood. We proposed (1) to characterize the neuropsychological profile of
      Behcet's disease patients with (Neuro-BD) and without (BD) neurological
      manifestations; (2) to identify which clinical, psychopathological, and genetic
      variables are related to neuropsychological performance; and (3) to explore the
      association between cognitive functioning and neuroimaging findings in BD
      patients. Fifteen Neuro-BD and 35 BD patients in the nonactive phase of their
      illness underwent a neurological examination, performed a comprehensive battery
      of neuropsychological tests, and answered the hospital anxiety and depression
      scale. Human leukocyte antigen (HLA)-B*51 genotyping was also performed.
      Patients' neuropsychological performances were compared to those of healthy
      demographically matched subjects. Within one month from the testing date, a
      subset of 20-BD patients underwent a magnetic resonance imaging (MRI) scan. Fifty
      three percent of Neuro-BD and 40% of BD patients were impaired at least on one
      neuropsychological measure (i.e., digit span-forward). Poorer cognitive
      functioning in Neuro-BD was associated with parenchymal involvement, whereas in
      BD it was related to presence of white matter changes in the frontal lobes,
      history of headache complaints, or higher levels of anxiety and depression.
      Current prednisone intake had a positive impact on neuropsychological
      performance. Disease duration, time since onset of neurological manifestations,
      or presence of HLA-B*51 allele had no significant influence. Our results indicate
      that Behcet's disease may affect cognitive abilities in the absence of overt
      neurological symptoms. These findings point to an insidious course of
      neurological involvement.

PMID- 19758155
TI  - Alexithymia in systemic lupus erythematosus patients.
AB  - This study aimed to determine the prevalence of alexithymic characteristics in
      patients with systemic lupus erythematosus (SLE), comparing them with a
      population of healthy subjects. Fifty-three SLE patients [American College of
      Rheumatology (ACR) criteria] and 31 healthy volunteer subjects were administered
      validated scales for alexithymia (Toronto alexythimia scale-20), psychopathology
      (brief symptom inventory; hospital anxiety and depression scale), personality
      dimensions (NEO five-factor inventory), and quality of life (short form-36 health
      survey). The SLE patient's clinical and laboratory evaluations were performed by
      computerized indicators of activity (SLE disease activity index), of accumulated
      damage (Systemic Lupus International Collaborating Clinics/American College of
      Rheumatology damage index), length of disease, and therapy. A high prevalence of
      alexithymia was found in SLE patients. Alexithymia was associated with
      psychopathology, personality, and quality of life dimensions. Clinical variables
      and therapy were not correlated significantly with alexithymia, psychopathology,
      or quality of life dimensions. Multiple regression analysis showed that openness
      and depression were the two predictors for alexithymia in SLE patients. The
      present findings showed that alexithymia may play an important role in SLE
      patients. The difficulty in the management of emotions may lead to psychological
      distress and instability affecting the patient's quality of life, a relevant
      finding for the psychological, psychiatric, and clinical intervention and
      approach.

PMID- 19758156
TI  - Anti-C1q antibodies in juvenile-onset systemic lupus erythematosus.
AB  - The objective of this study was to evaluate the presence of anti-C1q antibodies
      Hospital Israelita Albert Einstein Research Institute, Sao Paulo, Brazil in 67
      juvenile systemic lupus erythematosus (JSLE) patients and 26 healthy controls and
      to assess the association of these antibodies with disease activity, nephritis,
      and presence of anti-double-stranded (ds)DNA. Anti-C1q antibodies were detected
      by ELISA. A higher frequency of anti-C1q antibodies was observed in JSLE patients
      compared to controls (20% vs. 0%, P = 0.016). Specificity of these antibodies was
      100%[95% confidence interval (CI) 86.7-100%] and sensitivity was 19.4% (95% CI
      10.7-30.8%) for a lupus diagnosis. The median anti-C1q antibodies was higher in
      JSLE patients compared to controls [median (range) 9.4 (5.5-127) vs. 7.3 (5-20)
      units, P = 0.004]. Remarkably, a positive Spearman's coefficient was found
      between anti-dsDNA and anti-C1q units (r = 0.42, P = 0.0004, 95% CI 0.19-0.60).
      Our results confirm a low frequency of anti-C1q antibody in our lupus
      populations, but the presence of anti-Clq antibodies appears to be a good marker
      for JSLE diagnosis.

PMID- 19758157
TI  - A new year in autoimmunity.
AB  - Over the past year there have been several new developments in our understanding
      of autoimmunity, as well represented by several lines of evidence obtained from
      basic, translational, and clinical research alike. To summarize novel findings
      reported in 2008 this article will review selected publications from the most
      prominent scientific journals and ultimately suggest some links in the field of
      autoimmune diseases from leading journals dedicated to autoimmunity. The take
      home message from these readings is that autoimmunity ultimately becomes a
      uniform scenario in which similarities between conditions significantly outnumber
      differences in terms of pathogenesis and mechanisms.

PMID- 19758158
TI  - Relevance of anti-C1q autoantibodies to lupus nephritis.
AB  - The first component of the classical pathway of the complement system (C1q) is
      considered to have a crucial role in the clearance of immune complexes (ICs) as
      well as in the removal of waste material originating from apoptotic cells. A
      prolonged exposure of C1q epitopes to the immune system could eventually lead to
      an autoimmune response against itself. Although autoantibodies against C1q are
      found in several diseases, their clinical interest originates from their strong
      association to active lupus nephritis (LN). Several studies indicate that anti
      C1q autoantibodies could serve as a reliable serologic marker in the assessment
      of LN activity compared to other immunological tests. Additionally, it was
      suggested that anti-C1q autoantibodies could play a role in LN pathogenesis.
      Their potential pathogenic actions likely depend on genetic background, titers,
      Ig classes and subclasses, and specific epitopes of anti-C1q autoantibodies as
      well as C1q availability and allocation. It is still unclear which different
      types of anti-C1q autoantibodies dominate in each case and if their upregulation
      is pathogenic, an epiphenomenon of aberrant tissue damage, or compensatory to an
      uncontrolled immune response.

PMID- 19758159
TI  - Dysregulation of the vitamin D nuclear receptor may contribute to the higher
      prevalence of some autoimmune diseases in women.
AB  - Researchers have noted that the incidence of autoimmune diseases, such as
      Hashimoto's thyroiditis, is markedly higher in women than in men, but to date the
      reason for this disparity has been unclear. The vitamin D nuclear receptor (VDR)
      is expressed in the human cycling endometrium. Because the VDR controls
      expression of the cathelicidin and beta-defensin antimicrobial peptides (AmPs),
      dysregulation of the receptor greatly compromises the innate immune response.
      Increasing evidence indicates the presence of a chronic, intraphagocytic,
      metagenomic microbiota in patients with autoimmune disease that may survive by
      dysregulating the VDR. VDR dysregulation, in turn, prevents the breakdown of the
      active vitamin D metabolite 1,25-hydroxyvitamin D (1,25-D) by CYP24. In silico
      data suggest that when 1,25-D rises above its normal range, it binds the
      alpha/beta thyroid receptors, the glucocorticoid receptor (GCR), and the androgen
      receptor (AR), displacing their native ligands and causing an array of hormonal
      imbalances. If T3 is displaced from alpha-thyroid, thyroiditis may result.
      Because the VDR, GCR, and AR also express multiple families of AmPs, expression
      of these natural antibiotics further wanes in response to dysregulation by 1,25
      D. The end result is a system-wide drop in AmP expression that may allow
      pathogens to spread with greater ease. Because women have an extra site of VDR
      expression in the endometrium, the drop in AmP expression associated with nuclear
      receptor dysregulation may disproportionately affect them. This would cause women
      to accumulate higher bacterial loads than their male counterparts, particularly
      during early pregnancy when 1,25-D levels rise by 40%.

PMID- 19758160
TI  - Regulatory B cells in autoimmune diseases: how do they work?
AB  - B lymphocytes contribute to the pathogenesis of autoimmune disorders since B-cell
      depletion treatment improves such diseases. However, B cells seem ambivalent.
      Murine strains of nonorgan-specific as well as organ-specific autoimmune
      conditions present with aggravated symptoms when B cells are depleted. It is thus
      likely that some B cells are pathogenic while other have regulatory function.
      There is not only one regulatory B cell (Breg) subset, but different types of
      Breg cells. Regulatory function can thus be ascribed to autoreactive B cells,
      marginal zone B cells, transitional type 2-like B cells, or CD5(+) B cells.
      Regulatory activity is induced only following cell activation through a B-cell
      receptor, CD40, and/or TLR9. Regulatory effects are then mediated by a soluble
      agent, such as IL-10, and/or direct cell-to-cell contacts that involve CD40 or B7
      co-stimulatory molecules. Targeted cells also vary from one disease to another.
      Antigen-specific autoreactive T cells, dendritic cells, macrophages, and
      regulatory T lymphocytes can thus be either inhibited or activated to finally
      modulate the autoimmune response. Taken as a whole, it appears that Breg cells
      participate in the control of autoimmunity within a complex cellular network that
      may differ for each pathology. Adapted stimulation and control of regulatory
      activity would thus be a prerequisite to an efficient usage of these B cells as
      an alternative therapy for autoimmune diseases.

PMID- 19758161
TI  - B-lymphocyte stimulator and a proliferation-inducing ligand serum levels in IgA
      deficient patients with and without celiac disease.
AB  - IgA deficiency (IgAD) is the most common form of immunodeficiency and frequently
      associates with autoimmunity, especially with celiac disease (CD). The mechanisms
      underlying IgAD and the development of autoimmunity are still relatively unknown.
      Elevated B-lymphocyte stimulator (BLyS) and APRIL (a proliferation-inducing
      ligand) serum levels characterize several autoimmune diseases. We herein
      investigated BLyS and APRIL serum levels in IgAD patients with and without CD and
      compared these patients to CD patients with normal IgA and control patients
      (HBDs). Compared to HBDs, IgAD patients demonstrated a significant increase of
      BLyS (P < 0.0001) and APRIL (P = 0.003) levels, and no differences were seen
      between patients with or without CD. While BLyS appeared similarly overexpressed
      in IgAD and CD patients, APRIL was significantly increased only in IgAD patients.
      Because APRIL promotes IgA production, its overexpression may represent a
      physiological mechanism of compensation. BLyS upregulation may be involved in the
      increased risk of autoimmune disease development characterizing people carrying
      IgAD.

PMID- 19758162
TI  - The IgM response to modified LDL in experimental atherosclerosis: hypochlorite
      modified LDL IgM antibodies versus classical natural T15 IgM antibodies.
AB  - INTRODUCTION: It is hypothesized that IgM antibodies to oxidized LDL are anti
      atherogenic. Myeloperoxidase from plaque-infiltrating neutrophils catalyzes the
      production of hypochlorite (HOCl), which oxidizes LDL. Here we study the IgM
      response to HOCl-modified LDL in comparison to titers of T15 clonotypic natural
      antibodies. METHODS: Plasma of LDLR(-/-) mice fed a normal chow or high-fat diet
      was obtained after 6 and 16 weeks. The IgM responses to HOCl-modified LDL and T15
      clonotypic natural IgM antibodies were measured by ELISA. RESULTS: The IgM levels
      in response to HOCl-modified LDL increased dramatically in the atherosclerotic
      group after introduction of the high-fat diet, but not in mice on normal chow.
      The natural IgM T15 clonotypic antibody titers revealed a more moderate increase
      during atherogenesis. CONCLUSION: Our results show that during atherogenesis
      there is a strong induction of IgM antibodies to HOCl-modified LDL particles.
      Whether these induced IgM antibodies are pro- or anti-atherogenic remains to be
      established.

PMID- 19758163
TI  - IL-10 production by B cells expressing CD5 with the alternative exon 1B.
AB  - B lymphocytes are divided into two subpopulations, B1 and B2 cells based on
      expression of the T cell-associated protein CD5. Natural B1 cells are further
      divided into B1a cells that express CD5 on their membrane and B1b cells that do
      not but share most other biological characteristics of B1a cells. Recent studies
      from our laboratory have revealed, in humans, the existence of two alternative
      isoforms of the CD5 protein. A cell surface CD5 isoform which uses exon 1A (E1A)
      of the gene in B1a cells, and an intracellular isoform which uses exon 1B (E1B)
      mainly in human B1b cells. Indeed, the protein isoform encoded by transcripts
      containing E1B lack the leader peptide and is, thus, retained in the cytoplasm of
      B cells. The restriction of interleukin (IL)-10 to B1 lymphocytes in the mouse
      raises the possibility that the human CD5-E1B-expressing B cells produce IL-10.
      This prediction was confirmed in the CD5 negative Jok-1 B cells transfected with
      cDNA for either isoforms resulted in high level IL-10 production. Our data
      indicate that E1B-CD5-expressing B cells have the capacity to interfere with the
      immune response through their ability to produce high levels of IL-10.

PMID- 19758164
TI  - Cytokines and anxiety in systemic lupus erythematosus (SLE) patients not
      receiving antidepressant medication: a little-explored frontier and some of its
      brief history.
AB  - Autoimmunity travelled from the theoretical roots planted by Burnet with the
      clonal selection theory and the early finding of a mouse providing a test for the
      role of the thymus as a source of forbidden clones. This chapter briefly reviews
      early work with the NZB mouse and presents results of an analysis of associations
      between cytokines and physical and psychometric parameters in systemic lupus
      erythematosus (SLE) patients not medicated with antidepressants. Some cytokines,
      particularly IFN-gamma, relate significantly to physical symptoms and anxiety. We
      conclude with the speculation that anxiety is linked to innate immunity and more
      severe neuropsychiatric disease in SLE to adaptive immunity.

PMID- 19758165
TI  - Natural antibodies against phosphorylcholine in cardiovascular disease.
AB  - Atherosclerosis is a chronic inflammatory disease characterized by the presence
      of activated immune-competent cells in the lesions, producing mainly
      proinflammatory cytokines. Atherosclerosis is the underlying cause of
      cardiovascular disease (CVD), to a large extent occurring after damage and/or
      rupture of the atherosclerotic plaques. One major factor implicated as a cause of
      this immune activation is modified low-density lipoproteins (LDL), especially
      oxidized forms (oxLDL), which are abundant in plaques, both in foam cells and in
      the necrotic core. The LDL-oxidation process is very complex, and the nature of
      the antigens has been difficult to identify. We and others have focused on the
      phospholipids (PL) in oxLDL, especially oxidized forms of PL, including platelet
      activating factor (PAF)-like lipids and lysophosphatidylcholine (LPC), and
      demonstrated that these could play a major role through proinflammatory effects.
      One common epitope is phosphorylcholine (PC), which is also exposed on some
      microorganisms (including Streptococcus pneumoneae) and on apoptotic cells.
      Natural IgM antibodies against PC (anti-PC) have been known for a long time, but
      little has been reported about their role in human disease, especially in CVD. We
      have demonstrated that anti-PC IgM are negatively associated with atherosclerosis
      development in hypertensive individuals and that low levels of anti-PC
      independently predict development of CVD. Anti-PC IgM could, therefore, be a
      novel risk marker in CVD. Animal experiments indicate that both active
      immunization with PC and passive immunization with anti-PC ameliorate
      atherosclerosis development. The possibility that anti-PC could be used
      therapeutically in humans deserves further study.

PMID- 19758166
TI  - IL-18 activity in systemic lupus erythematosus.
AB  - Interleukin-18 (IL-18) is an inflammation-related cytokine that plays a central
      role both in innate defense reactions and in Th1 activation and specific immune
      responses. Increased levels of IL-18 can be detected in biological fluids and
      organs of individuals affected by several autoimmune pathologies, as well as in
      autoimmune animal models. In this review, the role of IL-18 in systemic lupus
      erythematosus (SLE) is critically examined, including its possible role in the
      pathogenesis of disease. In SLE, increased levels of IL-18 have been found in
      serum/plasma of affected persons, which positively correlated with disease
      severity. The possibility that circulating IL-18 levels are predictive of renal
      damage has been proposed, suggesting that IL-18 may be a prognostic marker of
      renal involvement useful to identify patients at risk of renal failure. The
      evaluation of urinary levels of free active IL-18 indeed suggests a correlation
      with the degree of renal involvement. The possible pathogenic role of IL-18 in
      lupus has been studied in a mouse model of progressive disease, which makes
      possible the identification, at the level of the different affected organs, of IL
      18 changes preceding disease development and those appearing after disease onset.
      It can be concluded that IL-18 has a multifaceted role in autoimmune lupus, being
      apparently involved both in the effector phases of the late organ damage and, in
      some organs, in the initial pathogenic events. Therapeutic strategies targeting
      IL-18 in autoimmunity are under development.

PMID- 19758167
TI  - CXCR3, inflammation, and autoimmune diseases.
AB  - CXCR3 is a G protein-coupled, seven-transmembrane receptor that binds and is
      activated by the three IFN-gamma-inducible chemokines of the CXC family named
      CXCL9, CXCL10, and CXCL11. These chemokines are not constitutively expressed but
      are up-regulated in a proinflammatory cytokine milieu. Consequently, their major
      function is to selectively recruit immune cells at inflammation sites, but they
      also play a role in angiogenesis mechanisms. In the last few years, strong
      experimental and clinical evidence has been obtained supporting the idea that the
      CXCR3 pathway is involved in the development of autoimmune diseases, especially
      by creating local amplification loops of inflammation in target organs, thereby
      inducing worsening of clinical manifestations. This article briefly reviews what
      we know today about the nature and functions of CXCR3, with special emphasis on
      its involvement in two main rheumatic systemic autoimmune diseases, namely
      rheumatoid arthritis and systemic lupus erythematosus.

PMID- 19758168
TI  - IL-6 during viral-induced chronic autoimmune myocarditis.
AB  - Interleukin (IL)-6 is a pleiotropic cytokine that plays a key role in a wide
      variety of diseases. Based on a number of adjuvant-induced experimental models,
      IL-6 is critical to the development of autoimmune diseases including experimental
      autoimmune encephalomyelitis, adjuvant-induced arthritis, and experimental
      autoimmune myocarditis. However, whether it plays a pathogenic role in viral
      induced autoimmune myocarditis has been less well defined. While experimental
      models of myocarditis have clearly linked IL-6 to the generation of pathogenic
      autoreactive T cells, IL-6 has exhibited a protective role in autoimmune disease
      development in viral-induced disease models. As pathogen infection has been
      linked to the majority of myocarditis patients, treatments aimed at decreasing IL
      6 levels in the hopes of limiting the autoimmune response run the risk of
      increasing disease severity.

PMID- 19758169
TI  - Clonal CD27+ CD19+ B cell expansion through inhibition of FC gammaIIR in HCV(+)
      cryoglobulinemic patients.
AB  - Persistent HCV infection may be associated with extrahepatic manifestations such
      as type II mixed cryoglobulinemia (II-MC), a clonal B cell proliferative
      disorder. In persistent HCV infection without II-MC, an increase in serum
      immunoglobulins (Ig) is commonly observed. This increase is polyclonal and is
      determined primarily by increased levels of IgG which include both HCV-specific
      and nonspecific antibodies. Nonetheless, memory CD27(+) B cells do not
      accumulate. This paradoxical phenomenon depends on heightened sensitivity of
      memory B cells to BCR-independent noncognate T cell help, which speeds up their
      terminal differentiation into antibody-secreting cells and makes them more prone
      to apoptosis. In persistent HCV infection with II-MC, serum Ig elevation is also
      a general occurrence, and characteristically includes IgM antibodies with
      rheumatoid factor activity, which are essential for the development of
      circulating, cryoprecipitable immune complexes. Hypergammaglobulinemia is
      sustained by a peripheral expansion of IgM(+)k(+)IgD(low/neg)CD21(low)CD27(+) B
      cells. These cells exhibit marked V(H), J(H), and V(K) gene segment usage
      restriction, indicating that a limited number of antigens drive their
      proliferation through BCR interaction. Recently, two epitopes, one of the human
      IgG and the second of the HCV(NS3) protein, had been identified and demonstrated
      able to link the BCR exposed on II-MC subjects. Based on the above findings, we
      propose a model whereby BCR binding the IgM/IgG/HCV(NS3) immune complexes
      deprives Fc gammaIIR of its natural ligand. This takes the brake off RF(+)CD27(+)
      B cell proliferation and promotes their selective accumulation, which is
      otherwise prevented by increased apoptosis susceptibility in persistent HCV
      infection without II-MC.

PMID- 19758170
TI  - Alterations in cytokine profile and dendritic cells subsets in peripheral blood
      of rheumatoid arthritis patients before and after biologic therapy.
AB  - Rheumatoid arthritis (RA) is an autoimmune disorder characterized by chronic
      joint inflammation and continuous immune cell infiltration in the synovium. These
      changes are linked to inflammatory cytokine release, leading to eventual
      destruction of cartilage and bone. During the last decade new therapeutic
      modalities have improved the prognosis, with the introduction of novel biological
      response modifiers including anti-TNFalpha CTLA4Ig and, more recently, anti-IL6.
      In the present study we looked at the immunological effects of these three forms
      of therapy. Serum, obtained from patients with RA was analyzed for TNFalpha, IL6,
      IL10, IFNgamma, and VEGF, and in parallel, circulating plasmacytoid and myeloid
      dendritic cells (DC) were enumerated before and after three infusions of the
      respective biological treatments. After treatment with anti-IL6, we found a
      significant reduction of IL6 and TNFalpha levels and the percentage of both DC
      subsets decreased. Although the results did not reach statistical significance
      for anti-TNFalpha treatment, similar trends were observed. Meanwhile, CTLA4Ig
      therapy led to the reduction IFNgamma levels only. None of the treatments
      modified significantly VEGF or IL10 levels. These findings may explain why
      patients with RA improve more rapidly on IL-6 therapy than with the other two
      modalities.

PMID- 19758171
TI  - Gluten sensitivity in multiple sclerosis: experimental myth or clinical truth?
AB  - Patients with neurological disease of unknown etiology sometimes present with
      antigliadin and antitissue transglutaminase antibodies. The association between
      these antibodies and multiple sclerosis has been previously suggested. The
      purpose of this study was to determine the prevalence of these antibodies in
      multiple sclerosis patients. We determined the level of serum immunoglobulin A
      and immunoglobulin G antigliadin and antitissue transglutaminase antibodies in 98
      patients with multiple sclerosis. We found a highly significant increase in
      titers of immunoglobulin G antibodies against gliadin and tissue transglutaminase
      in the multiple sclerosis patients. Seven patients had a positive IgG AGA,
      whereas only 2 controls presented positive titers (P = 0.03). Four patients had
      positive IgG anti-tTG while all the controls tested negative (P = 0.02). However,
      immunoglobulin A antibodies against gliadin and tissue transglutaminase were not
      statistically higher in the multiple sclerosis group in comparison to the control
      group. Our findings support the associations between antibodies against gliadin
      and tissue transglutaminase to multiple sclerosis. The specific role of these
      antibodies in the pathogenesis of multiple sclerosis remains uncertain and
      requires additional research. A gluten free diet should be considered in specific
      cases of patients who present with gluten antibodies.

PMID- 19758172
TI  - Chemokines as novel therapeutic targets for inflammatory bowel disease.
AB  - The inflammatory bowel diseases (IBD) such as Crohn's disease (CD) and ulcerative
      colitis (UC) are illness characterized by a chronic clinical course of relapse
      and remission associated with self-destructive inflammation of the
      gastrointestinal tract. In both UC and CD, leukocyte infiltration into the
      intestine is fundamental event in disease development and progression where the
      chemokines and their receptors are orchestrating the tissue-specific and the cell
      type-selective trafficking of leukocytes. In this review, we will discuss the
      homeostatic and inflammatory roles of the chemokines and their receptors with
      their potentials and promise as molecular targets for therapeutic interventions
      in human IBD, focusing on the recently identified role of the CX3CL1-CX3CR1 axis,
      as well as the CCL20-CCR6, CCL25-CCR9, and CXCL10-CXCR3 pathways.

PMID- 19758173
TI  - Galectin-10, eosinophils, and celiac disease.
AB  - Celiac disease (CD) is a chronic intestinal disease caused by intolerance to
      dietary wheat gluten in genetically susceptible individuals. There are a number
      of important open questions that impede the full explanation of the pathogenesis
      of this disease. We analyzed protein expression pattern in gut biopsies of CD
      subjects. Patients were selected and grouped according to histological
      inflammatory degree. Groups consisted of nine individuals with CD: three patients
      had a Marsh 0, three a Marsh I-II, and three a Marsh III. All CD patients showed
      a human leukocyte antigen DQ2/8 variant. Controls were three individuals with an
      excluded CD diagnosis. For the first time, galectin-10 expression was found
      related to the histological grade (P = 0.0092) and with the number of eosinophils
      in the lesion (P = 0.0040). Results suggest galectin-10 is a novel marker for
      evaluating CD tissue damage and eosinophils as a possible target for therapeutic
      approaches. Moreover, our data provide insights into alterations associated with
      CD tissue damage and pathogenesis.

PMID- 19758174
TI  - Defensins in systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease, resulting in
      inflammation and tissue damage. The precise etiology for SLE is so far unknown.
      It has been shown that the innate immunity plays a role in SLE pathogenesis. The
      innate immune system confers broad protection against pathogens by the secretion
      of broad-spectrum antibacterial and immunomodulatory substances named defensins.
      Recently, alpha-defensin, the products of neutrophils have been found to be
      upregulated at the mRNA and protein levels in SLE patients. In addition,
      increased antidefensin antibodies were found in sera of patients with SLE, but
      these levels decreased after therapy with corticosteroids. These recent findings
      suggest a role for defensins in the pathogenesis of SLE. Thus, activation and
      degranulation of neutrophils leads to alpha-defensin secretion in SLE patients.
      Given their immunomodulatory role, alpha-defensin secretion might activate the
      adaptive immune system leading to the stimulation of the immune system, as is
      manifested in SLE.

PMID- 19758175
TI  - Distribution of the NF-kappaB complex in the inflammatory exudates characterizing
      the idiopathic inflammatory myopathies.
AB  - The transcription factor nuclear factor-kappaB (NF-kappaB) is a ubiquitously
      expressed protein family that is considered crucial in autoimmunity. We describe
      NF-kappaB p50 and p65, and the inhibitor I-kappaB alpha in the inflammatory
      exudates characteristic for the different idiopathic inflammatory myopathies
      (IIM), that is, endomysial CD8(+) cytotoxic T cells invading non-necrotic fibers
      in polymyositis (PM) and sporadic inclusion body myositis (sIBM), and the
      perimysial/perivascular CD20(+) B cells and CD4(+) T cells in dermatomyositis
      (DM). We also analyzed other inflammatory cells in the vicinity of active
      inflammation sites. Strikingly, actively invading CD4(+) cells in PM and sIBM
      contained both p65 and p50, whereas I-kappaB alpha was absent. This could point
      to a high activation state in which these cells are capable of expressing a
      variety of inflammatory mediators, contributing to the degradation of non
      necrotic fibers. Secondly, CD68(+) macrophages in the infiltrates in all three
      IIM subtypes showed strong nuclear p50 and I-kappaB alpha staining. This may
      point to a role for p50 in counteracting inflammation, a reaction that could be
      enhanced by an upregulation of I-kappaB alpha as we observed with
      immunofluorescence. These results shed further light on the immunopathology of
      PM, sIBM and DM. CD4(+) and CD68(+) mononuclear cells may play a more prominent
      role than previously assumed.

PMID- 19758176
TI  - Sex differences in a murine model of Sjogren's syndrome.
AB  - Sex differences in a NOD.H2(h4) murine model of Sjogren's syndrome were analyzed.
      Compared to males, female NOD.H2(h4) mice have increased severity of
      sialoadenitis and have a significantly increased percentage of CD4(+) T cells in
      salivary gland infiltrates. CD4(+) T cells in female infiltrates produce more Th2
      and Th17 cytokines than in males, while males have greater Th1 responses. Females
      also have enhanced B cell responses, with higher levels of SSA and SSB serum
      antibodies, and B cell activation factor F (BAFF). Thus, sex has a strong impact
      on the severity of murine Sjogren's syndrome by affecting the immune mechanisms
      driving the autoimmune inflammation.

PMID- 19758177
TI  - Vitamin D metabolites as clinical markers in autoimmune and chronic disease.
AB  - Recent research has implicated vitamin D deficiency (serum levels of 25
      hydroxyvitamin D <50 nmol/L) with a number of chronic conditions, including
      autoimmune conditions such as multiple sclerosis, lupus, and psoriasis, and
      chronic conditions such as osteoporosis, osteoarthritis, metabolic syndrome,
      fibromyalgia and chronic fatigue syndrome. It has been assumed that low levels of
      25-hydroxyvitamin D (25-D) accurately indicate vitamin D storage and vitamin D
      receptor (VDR)-mediated control of calcium metabolism and innate immunity. To
      evaluate this assumption, 25-D and 1,25-dihydroxyvitamin D3 (1,25-D) levels were
      measured in 100 Canadian patients with these conditions. Additionally, other
      inflammatory markers (CK, CRP) were measured. Results showed a strong positive
      association between these autoimmune conditions and levels of 1,25-D >110 pmol/L.
      However, there was little association with vitamin D deficiency or the other
      inflammatory markers, meaning that the results challenge the assumption that
      serum levels of 25-D are a sensitive measure of the autoimmune disease state.
      Rather, these findings support the use of 1,25-D as a clinical marker in
      autoimmune conditions. High levels of 1,25-D may result when dysregulation of the
      VDR by bacterial ligands prevents the receptor from expressing enzymes necessary
      to keep 1,25-D in a normal range.

PMID- 19758178
TI  - Immmunopathogenesis of rheumatoid arthritis; induction of arthritogenic
      autoimmune responses by proinflammatory stimuli.
AB  - Rheumatoid arthritis (RA) is a severe autoimmune disorder of unknown etiology.
      Major autoantigens include immunoglobulin G (which is targeted by rheumatoid
      factor), citrullinated proteins, and the heterogeneous nuclear ribonucleoprotein
      (hnRNP) A2. To obtain more insight into the pathogenic role of arthritogenic
      autoantigens, we studied autoimmune responses in two animal models of RA, which
      are independent of immunization with exogenous antigens, namely human tumor
      necrosis factor-alpha (TNF-alpha)-transgenic (hTNFtg) mice and rats with pristane
      induced arthritis (PIA). Serologic and cellular studies revealed autoantibodies
      to hnRNP-A2 in these animals and pronounced T-cell reactivity to hnRNP-A2 and the
      presence of rheumatoid factor in PIA, while citrullinated antigens were not
      targeted. Furthermore, hnRNP-A2 was found to be highly overexpressed in the
      joints of mice and rats affected by arthritis. Thus, unspecific proinflammatory
      stimuli, such as TNF-alpha or pristane, may induce pathogenic autoimmune
      reactions that may drive an inflammatory process, leading to the development of
      erosive arthritis.

PMID- 19758179
TI  - Humoral mechanisms of atherogenesis.
AB  - The concept that atherosclerosis is an autoimmune disease is no longer
      controversial. Attention has been paid to cellular immune response, but current
      research is now focused on the humoral component of this complex disease. Heat
      shock proteins, oxidized low-density lipoproteins, beta2-glycoprotein 1,
      cardiolipins, and, more recently, high-density lipoproteins have been considered
      to be autoantigens that play a part in atherogenesis. The characterization and
      understanding of the mechanisms associated with the presence of these antigens
      and their respective autoantibodies might contribute to elucidating the
      atherosclerotic process. In the near future, immune modulation might constitute a
      very effective therapy of atherosclerosis.

PMID- 19758180
TI  - Microparticles and the hygiene hypothesis.
AB  - Departing from the functional parallelism that undoubtedly exists between the
      nervous and immune system, we suggest that the latter also counts with means for
      information exchange that may result in a mutual influence of immune processes
      between nearby individuals. Our concept relies on a molecular interface that is
      composed and, at the same time, interfered or modulated by the vast number of
      environmental agents from the surrounding milieu. We highlight the possibility
      that microparticles, previously shown to act as mediators of the transfer of
      receptors and other relevant immune molecules between distant cells, may
      represent a minor immune medium. In line with this argument, we envisage a
      potential role for the suggested interindividual immune link particularly in
      marginal conditions, such as those that shaped life in historical population
      centers or even in currently undeveloped countries. We speculate that
      overcrowding and unhygienic habits as dominant conditions may provide a suitable
      framework for the interconnection of individuals by means of their respective
      body wrapping microenvironments. As a corollary, we propose that collective means
      of defense may belong to the toolbox with which the immune system faces
      exceptional challenges. In the context, it seems highly suggestive to establish a
      link with the hygiene hypothesis. In this scenario, modern lifestyle appears as
      an interfering factor by dismantling the necessary conditions for the emergence
      of the immunological interface. Therefore, it is not implausible to confer to
      this modern 'immunological miscommunication' a role in current trends concerning
      the incidence of autoimmunity, allergy and chronic inflammation.

PMID- 19758181
TI  - Hyperactivity induced by antiphospholipid syndrome serum.
AB  - Antiphospholipid syndrome (APS) is a multisystem disorder characterized by
      arterial and venous thrombosis, pregnancy morbidity, and neuropsychiatric
      manifestations. Antiphospholipid IgG injected intracerebroventricularly (i.c.v.)
      cause behavioral hyperactivity in mice. In the present study we investigated the
      effects of APS whole-serum i.c.v. administration in female Balb/C mice. Control
      mice were injected with serum derived from healthy subjects or saline solution.
      Behavior was assessed by the staircase apparatus which combines locomotor (stair
      climbing) exploratory activities and rearing as a measure of anxiety. Mice
      injected with serum from APS patients or serum from normal subjects showed a
      trend to an increase in the number of stairs climbed in the APS group. The
      results suggest a differential effect of specific IgG and other serum components
      in the CNS manifestations of APS.

PMID- 19758182
TI  - Complement cascade in systemic lupus erythematosus: analyses of the three
      activation pathways.
AB  - The complement (C') cascade is an important part of the innate immunity. It acts
      through three major pathways: classical (CP), alternative (AP) and mannose
      binding-lectin (MP). C' reduction is a key feature in systemic lupus
      erythematosus (SLE), for its pathogenesis and for disease relapse. The aims of
      our study are to correlate C' variations with disease activity and verify the
      presence of C' deficiencies. We tested for three C' pathways 52 sera from 20
      patients affected by SLE. A significant correlation between the ECLAM score and
      the degree of activation of the CP (Mann-Whitney; P = 0.001) was recorded, while
      the correlation with anti-dsDNA antibodies did not reach statistical significance
      (Mann-Whitney; P > 0.05). In conclusion, the ELISA assay can be considered well
      suited for testing SLE samples. We detected a significant link between the phases
      of lupus activity and the reduction of the CP.

PMID- 19758183
TI  - The role of iNKT cells in the immunopathology of systemic lupus erythematosus.
AB  - An increasing body of evidence suggests that CD1d-restricted invariant natural
      killer T (iNKT) cells play an important immunoregulatory role in a variety of
      autoimmune diseases in both humans and mouse models. Their role in systemic lupus
      erythematosus (SLE), however, is not fully determined, as SLE mouse models have
      yielded conflicting results demonstrating both a protective function and a
      pathogenic role. The reduced frequency of iNKT cells in peripheral blood of lupus
      patients supports the idea of a protective role for these cells in the
      immunopathology of SLE. Therapeutic approaches using glycolipids provide a
      promising tool to correct numerical iNKT cell deficiencies and to modulate their
      function. This review highlights the potential role of iNKT cells in lupus
      immunopathology and summarizes recent studies concerning iNKT cells in SLE
      patients, lupus-prone murine models and glycolipid therapy.

PMID- 19758184
TI  - Autoimmunity triggers in the NOD mouse: a role for natural auto-antibody
      reactivities in type 1 diabetes.
AB  - The nonobese diabetic mouse (NOD) is widely used as a model to study human type 1
      diabetes (T1D). In the NOD mouse T1D is a T cell-mediated autoimmune disease of
      complex etiology in which B cells play an essential role. One of the major
      unresolved issues in T1D is the genetic and/or environmental factors that trigger
      the autoimmune reaction. In the NOD mouse, as in humans, auto-antibodies to
      pancreatic islets are present at early ages and are highly correlated to diabetes
      progression, but their etiological role has long been disputed. NOD auto
      antibodies have the characteristics of a natural repertoire, and B1 cells, the
      main natural antibody producers, exhibit functional differences in this strain
      that could have consequences for disease determination. Using a genetic approach,
      we propose to test if the NOD natural auto-antibody repertoire includes innate
      reactivities that participate in diabetes pathogenesis by promoting insulitis
      initiation.

PMID- 19758185
TI  - Oversecretion of cytokines and chemokines in lupus nephritis is regulated by
      intraparenchymal dendritic cells: a review.
AB  - Lupus nephritis (LN) occurs in more than one-third of patients with systemic
      lupus erythematosus. Its pathogenesis is attributed to the glomerular deposition
      of immune complexes as well as to imbalance of the cytokine homeostasis. In this
      context, high production of cytokines and chemokines by dendritic cells (DCs) may
      concur to LN. In addition, urinary cytokine excretion may reflect the
      accumulation of DCs within glomeruli. DCs are differentiated in both myeloid and
      plasmacytoid (p) subsets in relation to their typical antigen and chemokine
      expression. Both subsets migrate in response to chemotactic stimuli because pDCs
      are susceptible to IL-18 expressed by resident glomerular cells. pDCs bear the IL
      18R, and it is conceivable that DCs migrate to the kidney under the attraction of
      IL-18. Therefore, the depletion of DCs reflects the inflammation severity in LN,
      whereas measurement of Th1 cytokines may represent an effective tool for
      monitoring the onset of LN.

PMID- 19758186
TI  - Toll-like receptors in multiple sclerosis mouse experimental models.
AB  - Certain pathogen molecules trigger innate immune responses and drive subsequent
      adaptive immune responses toward an antigen presented simultaneously. Such
      bacterial or viral molecules constitute pathogen-associated molecular patterns
      (PAMPs) that bind to pattern-recognition receptors such as toll-like receptors
      (TLRs). Recently, endogenous molecules were identified that ligate the same
      receptors. The role of these receptors' response to complete Freund's adjuvant
      during initiation of CD4 T cell responses in EAE, the animal model for multiple
      sclerosis, is here discussed. Myeloid differentiation primary response gene 88
      (MyD88) is necessary for the induction of experimental autoimmune
      encephalomyelitis (EAE), and it is required for the activation of myeloid
      dendritic cells and differentiation of T helper 17 cells. The role of individual
      TLR, in particular TLR3, TLR4, and TLR9, signaling in modulation of EAE
      inflammation varies with the experimental model employed and the immune cells
      that drive pathology. The TLR-dependent production of proinflammatory cytokines
      is regulated by mechanisms that dampen the pathway and prevent excess damage.
      Development of TLR antagonists to treat autoimmune diseases must acknowledge the
      possibility of interference with regulatory mechanisms.

PMID- 19758187
TI  - A dual role for HSP90 and HSP70 in the inflammatory myopathies: from muscle fiber
      protection to active invasion by macrophages.
AB  - Chaperones assist the metamorphosis of polypeptides to fully functional proteins.
      The family of heat shock proteins 70 (HSP70) bind at an early stage, while the
      HSP90 bind to proteins near their active conformation. We studied HSP90 and HSP70
      in muscle biopsies from controls and patients diagnosed with the three main
      idiopathic inflammatory myopathies (IIM), namely dermatomyositis (DM), sporadic
      inclusion body myositis (IBM), and polymyositis (PM). Human skeletal muscle
      displayed constitutive levels of protein, but in IIM both HSP90 and HSP70 were
      upregulated. Regenerating muscle fibers of IIM and muscular dystrophy patients
      showed increased expression of HSP90 and HSP70, as did atrophic perifascicular
      muscle fibers of DM and vacuolated fibers of IBM. The infiltrates of IIM
      displayed weak homogeneous HSP70 staining. HSP90 were specifically upregulated in
      the CD68(+) cells, actively invading non-necrotic muscle fibers of IBM/PM and co
      localized with inducible NO synthase. HSP90:HSP70 ratios were increased in IBM
      and PM tissues displaying high inflammation grade. Our results point to a
      multifaceted role for chaperones in muscle tissue: a general protective role for
      both HSP90 and HSP70 families in damaged muscle fibers, and a specific cytotoxic
      role for HSP90 in muscle fiber invasion typically associated with IBM and PM.

PMID- 19758188
TI  - NGF and its receptor system: a new dimension in the pathogenesis of psoriasis and
      psoriatic arthritis.
AB  - A contributing role of nerve growth factor (NGF)-mediated neuroimmunologic
      mechanisms has provided a new dimension in the understanding of various cutaneous
      and systemic inflammatory diseases. Recent evidence implicates NGF as a key
      mediator of inflammation and pain. NGF influences an inflammatory reaction by
      regulating neuropeptides, angiogenesis, cell trafficking molecules, and T cell
      activation. All of these functions of NGF are relevant in maintenance or
      initiation of the critical biologic events in various rheumatologic conditions.
      The recognition of a pathologic role of NGF and its receptor system has provided
      an attractive opportunity to develop a novel class of therapeutics for
      inflammatory diseases and chronic pain syndromes. In this chapter we will discuss
      the role of NGF and its receptor system in psoriatic disease, inflammatory
      arthritis, and arthritic pain of osteoarthritis.

PMID- 19758189
TI  - Effector functions of antiaquaporin-4 autoantibodies in neuromyelitis optica.
AB  - NMO-IgG autoantibody is now considered a useful serum biomarker of neuromyelitis
      optica (NMO). A series of clinical and pathological observations suggest that NMO
      IgG may play a central role in NMO physiopathology. Although the exact role and
      function of NMO-IgG in vivo remain to be determined, recent reports suggest that
      this antibody that targets the aquaporin-4 (AQP-4) water channel expressed by
      astrocytes is able to destabilize the blood-brain barrier and contribute to
      astrocyte and oligodendrocyte damage. This review summarizes the latest molecular
      effector functions attributed to the NMO-IgG/anti-AQP4 antibody and discusses
      their potential role in NMO pathology.

PMID- 19758190
TI  - Preventing viral-induced type 1 diabetes.
AB  - The development of type 1 diabetes is, in part, dictated by the failure of
      regulatory T cells to maintain peripheral tolerance. As such, therapies aimed at
      correcting the declining function of regulatory T cells have been the subject of
      intense investigation. In this review, we discuss the potential of regulatory T
      cells to suppress autoreactive responses and prevent type 1 diabetes induced by
      viral infection while maintaining protective antiviral immunity.

PMID- 19758191
TI  - Shared and unique gene expression in systemic lupus erythematosus depending on
      disease activity.
AB  - Patients presenting with active systemic lupus erythematosus (SLE) manifestations
      may exhibit distinct pathogenetic features in relation to inactive SLE. Also,
      cDNA microarrays may potentially discriminate the gene expression profile of a
      disease or disease variant. Therefore, we evaluated the expression profile of
      4500 genes in peripheral blood lymphocytes (PBL) of SLE patients. We studied 11
      patients with SLE (seven with active SLE and four with inactive SLE) and eight
      healthy controls. Total RNA was isolated from PBL, reverse transcribed into cDNA,
      and postlabeled with Cy3 fluorochrome. These probes were then hybridized to a
      glass slide cDNA microarray containing 4500 human IMAGE cDNA target sequences. An
      equimolar amount of total RNA from human cell lines served as reference. The
      microarray images were quantified, normalized, and analyzed using the R
      environment (ANOVA, significant analysis of microarrays, and cluster-tree view
      algorithms). Disease activity was assessed by the SLE disease activity index.
      Compared to the healthy controls, 104 genes in active SLE patients (80 repressed
      and 24 induced) and 52 genes in nonactive SLE patients (31 induced and 21
      repressed) were differentially expressed. The modulation of 12 genes, either
      induced or repressed, was found in both disease variants; however, each disease
      variant had differential expression of different genes. Taken together, these
      results indicate that the two lupus variants studied have common and unique
      differentially expressed genes. Although the biological significance of the
      differentially expressed genes discussed above has not been completely
      understood, they may serve as a platform to further explore the molecular basis
      of immune deregulation in SLE.

PMID- 19758192
TI  - Association of polymorphisms in interleukin-10 gene promoter with autoantibody
      production in patients with rheumatoid arthritis.
AB  - Interleukin-10 (IL-10) is a major anti-inflammatory cytokine that plays a crucial
      role in the regulation of the immune system. Allelic polymorphisms in the IL-10
      gene promoter may contribute to the regulation of autoantibody production. To
      examine the association between both individuals IL-10 single nucleotide
      polymorphisms and the production of autoantibodies and the radiographic
      progression of rheumatoid arthritis (RA), a total of 144 RA patients were
      recruited into the study. We found significant differences in genotype
      distribution of the -1082G/A polymorphism between IgG, IgA, and IgM rheumatoid
      factor(RF)-positive/negative RA patients. We also found significant differences
      in allelic frequencies of the -3575T/A, -819C/T, and -592A/C polymorphisms
      between anticyclic citrullinated peptide (anti-CCP)-positive/negative RA
      patients. The haplotype TGAATA was found to be less frequent within anti-CCP
      positive RA patients. Results obtained in this study provide evidence of an
      association between polymorphisms in IL-10 gene promoter and the production of
      autoantibodies in RA patients.

PMID- 19758193
TI  - Val/Leu247 polymorphism of beta2-glycoprotein I in Brazilian patients with
      antiphospholipid syndrome--a genetic risk factor?
AB  - A genetic polymorphism of the beta2-glycoprotein I (beta2-GPI) is recognized by
      antiphospholipid antibodies (aPL) and may even play a role in the development of
      antiphospholipid syndrome (APS). The objectives of this study were to determine a
      Val/Leu SNP at position 247 of the beta2-GPI gene in Brazilian patients with APS
      and to compare these data with clinical and laboratory manifestations.
      Polymorphism assignment was performed by PCR followed by Rsa I restriction
      endonuclease. The titration of anti-beta2-GPI antibodies was detected by ELISA.
      The results showed significantly higher frequencies of the V-encoding allele and
      the homozygous VV genotype in patients with APS than in control subjects (OR =
      1.781, P = 0.0068; and OR = 6.413, P < 0.0001, respectively). The frequency of
      this genotype was also significantly higher in patients with arterial and venous
      thrombosis than in the control group (52% and 44%, respectively, versus 13%).
      Anti-beta2-GPI-positive patients had significantly higher frequencies of the VV
      genotype than the controls subjects (OR = 8.179, P < 0.0001). These results
      suggest that the V-encoding allele and the homozygous VV genotype at position 247
      of the beta2-GPI gene may play a role in the generation of anomalous beta2-GPI,
      with consequent auto-antibody production, and in phenotype expression of arterial
      and venous thrombosis in APS patients.

PMID- 19758194
TI  - Association study on two vitamin D receptor gene polymorphisms and vitamin D
      metabolites in multiple sclerosis.
AB  - BACKGROUND: An association of two single-nucleotide polymorphisms (SNPs) of the
      vitamin D receptor (VDR) gene, Apal (rs7975232) and Taql (rs731236), with
      multiple sclerosis (MS) has been reported in a Caucasian population. Another SNP
      of the VDR gene, Fokl (rs10735810), has been associated with serum levels of 25
      hydroxyvitamin D [25(OH)D]. OBJECTIVE: Since 25(OH)D status has been associated
      with MS incidence, we assessed the association Apal and Taql with the serum
      levels of 25(OH)D and 1,25(OH)(2)D, and MS in our population. METHODS: We
      determined the two SNPs as well as the summer and winter period serum levels of
      25(OH)D and 1,25(OH)(2)D in 212 MS patients. Additionally, we genotyped 289
      healthy controls and determined the metabolite levels. RESULTS: The genotype and
      allele distribution of the two VDR gene SNPs did not differ between patients and
      controls. There was no association of the Apal and Taql SNPs with 25(OH)D levels,
      1,25(OH)(2)D levels, or 1,25(OH)(2)D/25(OH)D ratios in patients or controls.
      DISCUSSION: We found no association of the Apal and Taql VDR gene SNPs with MS or
      with vitamin D metabolism in our population. Further research should assess the
      complex interaction between vitamin D, the VDR, and susceptibility to MS.

PMID- 19758195
TI  - Genetic susceptibility loci in rheumatoid arthritis establish transcriptional
      regulatory networks with other genes.
AB  - Linkage studies have identified the human leukocyte antigen (HLA)-DRB1 as a
      putative rheumatoid arthritis (RA) susceptibility locus (SL). Nevertheless, it
      was estimated that its contribution was partial, suggesting that other non-HLA
      genes may play a role in RA susceptibility. To test this hypothesis, we conducted
      microarray transcription profiling of peripheral blood mononuclear cells in 15 RA
      patients and analyzed the data, using bioinformatics programs (significance
      analysis of microarrays method and GeneNetwork), which allowed us to determine
      the differentially expressed genes and to reconstruct transcriptional networks.
      The patients were grouped according to disease features or treatment with tumor
      necrosis factor blocker. Transcriptional networks that were reconstructed allowed
      us to identify the interactions occurring between RA SL and other genes, for
      example, HLA-DRB1 interacting with FNDC3A (fibronectin type III domain containing
      3A). Given that fibronectin fragments can stimulate mediators of matrix and
      cartilage destruction in RA, this interaction is of special interest and may
      contribute to a clearer understanding of the functional role of HLA-DRB1 in RA
      pathogenesis.

PMID- 19758196
TI  - Genetic and epigenetic control of the major histocompatibility complex class Ib
      gene HLA-G in trophoblast cell lines.
AB  - The transcriptional regulation of the major histocompatibility complex class
      (MHC) Ib gene HLA-G differs from the classical MHC class I genes. The cis-acting
      regulatory elements typical for classical MHC class I promoters are divergent in
      the promoter of HLA-G, rendering this gene unresponsive to NF-kappaB, IRF-1, and
      class II transactivator (CIITA)-mediated activation pathways. However, as we have
      previously shown, transactivation of HLA-G is regulated by CREB-1. Because CREB-1
      is ubiquitously expressed, this observation does not explain the tissue
      restricted expression of HLA-G in extravillous cytotrophoblasts. Using HLA-G
      expressing JEG-3 cells and HLA-G-deficient JAR trophoblast-derived
      choriocarcinoma cells as a model, we have investigated the contribution of DNA
      methylation and histone acetylation in the transcriptional activation of HLA-G.
      Despite similar levels of DNA methylation both in JEG3 and JAR cells, we found
      the levels of histone acetylation in HLA-G promoter chromatin to be significantly
      enhanced in JEG3 cells coinciding with HLA-G expression.

PMID- 19758197
TI  - Human leukocyte antigen-DRB1 and -DQB1 genotyping in lupus patients with and
      without antiphospholipid syndrome.
AB  - We investigated the genetic background regarding major histocompatibility complex
      (MHC) II alleles in patients with systemic lupus erythematosus (SLE) only, in
      patients with SLE with secondary antiphospholipid syndrome (SLE+SAPS), and in
      patients whose clinical course began as primary antiphospholipid syndrome (PAPS)
      and subsequently progressed to SLE (PAPS+SLE) in order to explain the
      phenotypical differences found in our previous study. Those with primary or
      secondary APS present more thrombotic and less inflammatory activity. Fetal
      wastage was the highest in the PAPS+SLE group. We performed human leukocyte
      antigen (HLA)-DRB1 and HLA-DQB1 genotyping in 63 patients (26, 22, and 15 in SLE
      only, SLE+SAPS, and PAPS+SLE groups, respectively) and in 57 healthy controls,
      using PCR with sequence-specific primers. We found that, as reported in the
      literature, the occurrence of DRB1*03 and DQB1*0201 alleles was higher in SLE
      patients than in controls, but these alleles were rare in the PAPS+SLE group (13%
      in PAPS+SLE vs. 46% in the SLE only group; P = 0.044). HLA-DRB1*04 alleles were
      expressed frequently in both primary and secondary APS. DRB1*13, DQB1*06, and
      DQB1*0302 alleles were present more frequently in the PAPS+SLE patients than in
      the other groups, while the DQB1*0301 allele was rare. In this study we have
      shown that the SLE-associated DRB1*03/DQB1*02 alleles occurred frequently in our
      lupus patients as well as in SLE patients with secondary APS. In patients who
      started as PAPS and later progressed to SLE, the allele frequency was
      fundamentally different. Taken together, our results confirmed that the HLA-DRB1
      and HLA-DQB1 profile of PAPS and SAPS is different. Therefore it is unlikely that
      these alleles are responsible for the partly similar phenotype of the two groups.

PMID- 19758198
TI  - Race differences in immunogenetic features and photosensitivity of cutaneous
      lupus erythematosus from the aspect of Japanese studies.
AB  - Skin lesions of collagen diseases are influenced by environmental triggers, such
      as UV light, and are variable in cutaneous lupus erythematosus (LE), such as
      systemic LE (SLE), chronic discoid LE (CDLE), subacute cutaneous LE (SCLE), and
      LE tumidus (LET). Although there are a few conflicting reports on
      photosensitivity in collagen diseases, many Japanese dermatologists feel there
      are photosensitivity differences in LE between Asians and Caucasians with SCLE
      and LET. To address this issue, we have carried out genetic studies of Japanese
      SLE and CDLE patients and reviewed the race differences in photosensitivity of
      cutaneous LE from Japanese studies. Human leukocyte antigen (HLA) studies in
      Japanese patients revealed that HLA-DRB1*1501 association was with CDLE and SLE.
      The association between HLA-Cw6 and CDLE was first reported in a Japanese
      population, and a HLA-A33-B44-DRB1*1302 haplotype showed a positive association
      in CDLE. However, these results are not compatible with those from Caucasian
      subjects. There are no significant associations among HLA studies,
      photosensitivity, and anti-Ro/SS-A antibodies in Japanese CLE patients.
      Photosensitivity will be a key factor to dissolve multifactorial complexes of LE
      etiopathogenesis. An axis of photosensitivity, anti-Ro/SS-A antibodies, and
      apoptosis via tumor necrosis factor-alpha is the best marker to verify the
      contribution of genetics in CLE patients. The incidence and degree of
      photosensitivity of SCLE and LET are much lower in Japanese than in Caucasians.
      This discrepancy may lead to investigations of CLE pathogenesis through global
      collaborations.

PMID- 19758199
TI  - TNF-alpha polymorphisms in primary biliary cirrhosis: a northern and southern
      Italian experience.
AB  - Specific HLA alleles and immunoregulatory genes have been evaluated in primary
      biliary cirrhosis (PBC), but data are discordant. We determined whether TNF-alpha
      promoter polymorphisms (G-308A and G-238A) and alleles of HLA class II (HLA-DRB1)
      might be associated either with PBC occurrence and severity in Italian
      populations from two distinct areas. The distribution of TNF1 (G/G) genotype did
      not differ either between patients and controls or between patients from Northern
      and Southern Italy. Contrariwise, the HLA-DRB1*08 appeared positively linked to
      the occurrence of disease (8.4% in patients vs. 2.5% in controls, P = 0.003),
      whereas the HLA-DRB1*13 appeared to be protective, being more frequent in
      controls (12.8%) than in patients (7%) (P = 0.038). Neither positively nor
      negatively associated alleles of the two genomic loci had an effect on disease
      progression. We report a distinct genetic risk of developing PBC in the Italian
      population, with no interaction between the HLA and TNF alleles.

PMID- 19758200
TI  - HLA-B27 and HLA-B51 determination in Tunisian healthy subjects and patients with
      suspected ankylosing spondylitis and Behcet's disease.
AB  - The aim of this retrospective study is to assess the frequency of HLA-B27 and HLA
      B51 in healthy subjects from the center of Tunisia and to investigate their
      usefulness in the diagnosis of ankylosing spondylitis (AS) and Behcet's disease
      (BD), respectively. Microlymphocytotoxicity test was used to perform serologic
      HLA typing in a group of 124 healthy volunteers and a group of 365 patients
      suffering from clinical manifestations of AS and/or BD. HLA-B27 was found in 3.2%
      of healthy subjects and in 42.9% of patients with AS (P < 0.00006). HLA-B51 is,
      however, found in 16.1% of healthy subjects and in 30.0% of patients with BD (P >
      0.05). Unlike HLA-B51, which seems to be as frequent in Tunisian patients with BD
      as in healthy subjects, HLA-B27 is more frequent in patients with AS than in
      controls. This highlights the usefulness of HLA-B27, rather than that of HLA-B51,
      in the diagnosis of the respective diseases.

PMID- 19758201
TI  - HLA-B27 transgenic rat: an animal model mimicking gut and joint involvement in
      human spondyloarthritides.
AB  - The HLA-B27 gene is strongly associated with the spondyloarthropathies (SpA), a
      group of chronic inflammatory diseases affecting the bowel, the joints, and the
      axial skeleton. Yet the basis for this association remains unknown, despite
      extensive study in the past years. The HLA-B27 transgenic rat spontaneously
      develops a disease that strikingly resembles human SpA. The purpose of this
      article is to review the contribution of studies on the HLA-B27 transgenic rat
      model aimed to elucidate the intimate relationship between gut and joint
      involvement in SpA.

PMID- 19758202
TI  - HLA in Portuguese systemic lupus erythematosus patients and their relation to
      clinical features.
AB  - Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease
      translating the different genetic and environmental factors involved.
      Polymorphisms at several loci, including the major histocompatibility complex
      (MHC), have been associated worldwide with SLE, although inconsistencies exist
      among these studies mainly due to genetic heterogeneity between populations and
      sample characteristics. The aim of the present study was to investigate in
      Portuguese SLE the association of HLA-DRB1 alleles with clinical patterns of the
      disease and severity. Two hundred eighteen Portuguese patients with SLE--42% of
      whom had kidney involvement--were studied for HLA-DRB1. Clinical and laboratory
      manifestations were correlated with HLA allele frequencies. HLA-DRB1 * 03 allele
      frequency was significantly higher in SLE patients--as a whole and as either with
      or without renal involvement--compared to controls, while HLA-DRB1 * 09 and DRB1
      * 13 allele frequencies were decreased. Regarding the relationship with the
      presence or absence of specific clinical manifestations, it was only found that
      HLA-DRB1 * 08 allele frequency was increased in patients with neurological
      involvement. No association with the presence or absence of anti-dsDNA, anti-sm
      or antiphospholipid antibodies, or antiphospholipid syndrome, was observed. These
      results were reproducible when analysis was repeated only with patients with more
      than 5 years of evolution. As in other populations HLA-DRB1 * 03 is a
      susceptibility allele in Portuguese SLE patients, while HLA-DRB1 * 09 and DRB1 *
      13 alleles may be protective alleles, not only for the disease, but for the
      development of nephritis. No correlations with the different clinical
      manifestations were found, except with the neurological system.

PMID- 19758203
TI  - Ankylosing spondylitis susceptibility and severity--contribution of TNF gene
      promoter polymorphisms at positions -238 and -308.
AB  - Ankylosing spondylitis (AS) is a chronic inflammatory disease in which genetic
      factors play a central role. The efficacy of TNF blockers has reoriented research
      in this field in order to explain the influence of TNF in AS pathogenesis. The
      objective of this study was to access the influence of single nucleotide
      polymorphisms (SNPs) at positions -308 and -238 of the promoter region of TNF
      gene on AS susceptibility and prognosis. SNPs were determined by restriction
      fragment length polymorphisms in patients and controls. AS patients exhibited a
      decreased frequency of the A allele at position -238 (10%) when compared with
      controls (18%), suggesting that this could be a protective factor for disease
      susceptibility. In addition, the -308 GA/AA genotypes were associated with later
      disease onset in AS patients. These results suggest that TNF gene promoter
      polymorphisms at positions -238 and -308 could have a small influence on AS
      susceptibility and prognosis.

PMID- 19758204
TI  - Autoantibodies, polymorphisms in the serotonin pathway, and human leukocyte
      antigen class II alleles in chronic fatigue syndrome: are they associated with
      age at onset and specific symptoms?
AB  - This study aimed to determine the influence of autoantibodies, polymorphisms in
      the serotonin pathway, and human leukocyte antigen (HLA) class II genes on age at
      chronic fatigue syndrome (CFS) onset and symptoms. Eighty-one CFS patients were
      enrolled, and clinical data were recorded. Autoantibodies to different components
      of the central nervous system were tested. Polymorphisms in the promoter of the
      serotonin transporter gene (l/s) and a single nucleotide polymorphism in the
      serotonin receptor-2A gene (A/G) as well as HLA class II alleles were determined.
      Multivariate logistic-regression analyses were carried out. The mean age at CFS
      onset +/- SD was 33.5 +/- 12.5 years. An age at CFS onset (ACFSO) during the
      third decade of life was associated with the serotonin receptor AA genotype and
      the HLA-DRB1*03 allele. An ACFSO during the fourth decade of life was associated
      with the HLA-DRB1*07 allele, whereas an ACFSO > or = 43 years was associated with
      having at least one copy of the serotonin G allele. Concerning CFS symptoms, the
      serotonin AG genotype was protective against depressive symptoms. Although having
      at least one copy of the serotonin A allele and being female were associated with
      risk for arthralgia, the presence of antineuronal cell antibodies was protective
      against this. Episodes of unexplained fever were associated with the HLA-DRB1*11
      allele. None of the genetic or serological features was associated with myalgia.
      None of the antibodies determined correlated with any ACFSO or other symptoms.
      Our results reveal that in CFS, like other autoimmune diseases, different genetic
      features are related to age at CFS onset and symptoms.

PMID- 19758205
TI  - Infection, vaccination, and autoantibodies in chronic fatigue syndrome, cause or
      coincidence?
AB  - Chronic fatigue syndrome (CFS) is a heterogeneous syndrome of unknown etiology
      and physiopathology. CFS patients complain about disabling fatigue, depression,
      difficulty with memory, and concomitant skeletal and muscular pain. Interestingly
      enough, there is certain overlap between CFS symptoms, autoimmune rheumatic
      disease, and infectious diseases. Certain neuroendocrine-immune abnormalities
      have also been described, and autoantibodies commonly described in some
      autoimmune diseases have been found in CFS patients as well. An increasing number
      of autoantibodies, mainly directed against other nuclear cell components, have
      been illustrated. Likewise, an association between some infectious agents,
      antibody production, and later CFS onset has been reported. Similarly,
      vaccination is depicted as playing an important role in CFS onset. Recently, a
      case report pointed toward a causal association between silicone breast linkage,
      hepatitis B virus vaccination, and CFS onset in a previous healthy woman. Such
      findings suggest that there is a likely deregulation of the immune system
      influenced by specific agents (infections, vaccination, and products, such as
      silicone). Evidence suggests that CFS is a complex disease in which several risk
      factors might interact to cause its full expression. Thus, although different
      alterations have been found in CFS patients, undoubtedly the main feature is
      central nervous system involvement with immunological alterations. Therefore, a
      new term neuro-psycho-immunology must be quoted. New studies based on this
      concept are needed in order to investigate syndromes, such as CFS, in which
      immunological alterations are thought to be associated with concomitant
      psychological and health disturbances.

PMID- 19758206
TI  - Immunizations in adult patients with systemic sclerosis.
AB  - Immunizations are among the most efficient interventions available to prevent
      infectious diseases. However, there are no specific recommendations regarding
      vaccination in patients with systemic sclerosis (SSc). The aim of this review is
      to propose guidelines concerning immunization for patients with SSc. For SSc
      patients routine vaccine coverage should be assessed, including live vaccines,
      which are contraindicated after immunosuppressive therapy initiation;
      immunization against influenza and pneumococcus should be given especially in
      patients with pulmonary involvement and those receiving immunosuppressive
      therapy. To limit the risk of vaccine-preventable disease transmission to SSc
      patients, immunization of close contacts and healthcare professionals against
      influenza, measles-mumps-rubella, and varicella should be offered routinely. In
      conclusion, there is potential for serious illness and death in the
      underimmunization of high-risk patients, including those with SSc, and every
      effort should be made to ensure adequate protection through immunization.

PMID- 19758207
TI  - Influenza and autoimmunity.
AB  - Influenza infection can cause mild to severe illness and can even lead to death.
      The best way to prevent infection is vaccination against influenza. Complications
      of influenza infection are not only a consequence of acute infection but can also
      present as late autoimmune response. Influenza is not frequently implicated as a
      trigger for autoimmune diseases, but case reports of autoimmune adverse events
      have been published even following influenza vaccination. In this article we
      review published data on autoimmune diseases following influenza infection and
      vaccination. We also discuss immunity of influenza infection in connection to
      pathogenesis of autoimmune response and autoimmune disease.

PMID- 19758208
TI  - The role of infections in the immunopathogensis of systemic sclerosis--evidence
      from serological studies.
AB  - Infections are believed to often play a role in the immunopathogenesis of
      autoimmune disorders; such is the case in systemic sclerosis (SSc). In order to
      evaluate the potential role infections may have on the pathogenesis of SSc, we
      assessed serological reactivity against various infectious agents in patients
      with SSc and compared them with healthy controls. Serological samples obtained
      from 80 patients with SSc were compared with 296 compatible healthy controls.
      Both groups were of European origin. All samples were tested for the presence of
      antibodies directed against hepatitis B virus, hepatitis C virus, toxoplasmosis,
      rubella, CMV, EBV, and Treponema pallidum. We applied Bio-Rad commercial and
      experimental kits to assess most antigens and ELISA assays to complete the panel.
      Patients with SSc had elevated IgM and IgG against Toxoplasma gondii and against
      CMV. Higher titers were also detected against the hepatitis B virus core protein
      (recombinant HBc antigen) using MONOLISA anti-HBc Plus commercial kit (Bio-Rad).
      A significantly higher rate of IgM antibodies against the capsid antigen of the
      EBV was detected in SSc patients compared with healthy controls, as well. These
      data demonstrate that antibodies against CMV, HBV, and toxoplasmosis were
      detected more often in patients with SSc. This association implies that
      infectious agents may have a role in disease pathogenesis and expression.

PMID- 19758209
TI  - Anti-infectious antibodies and autoimmune-associated autoantibodies in patients
      with type I diabetes mellitus and their close family members.
AB  - Type 1 diabetes mellitus (T1DM) is an autoimmune disease with complex
      interactions between genetic and environmental factors. We compared antibody
      levels to various infectious agents and of autoimmune-associated autoantibodies
      between Colombian T1DM patients, their close family members and healthy controls.
      Significantly lower levels of antibodies against several infectious agents were
      detected in the T1DM patients. These included Helicobacter pylori (P = 0.01),
      cytomegalovirus (P = 0.001), Epstein-Barr virus (P = 0.02) and Toxoplasma (P =
      0.001). T1DM patients had significantly higher levels of IgG-anti-gliadin
      antibodies (P = 0.001) and IgG-antitissue transglutaminase antibodies (P = 0.03),
      and a borderline association with anticentromere antibodies (P = 0.06). The lower
      level of antibodies against infectious agents in T1DM patients may be related to
      their younger ages, but may also point to a protective role of those infections
      in T1DM development in susceptible individuals. Our results confirm the
      association between T1DM and celiac disease. A possible association with
      anticentromere antibody needs further studies.

PMID- 19758210
TI  - Infectious serologies and autoantibodies in inflammatory bowel disease:
      insinuations at a true pathogenic role.
AB  - The aim of this study was to reevaluate the role of infection in inflammatory
      bowel disease (IBD). Sera from 119 patients with IBD [80 with Crohn's disease
      (CD); 39 with ulcerative colitis] and 98 healthy controls were assessed using the
      Bio-Rad BioPlex 2200 for the presence of Toxoplasma gondii, cytomegalovirus,
      Epstein-Barr virus, Treponema pallidum, and Saccharomyces cerevisiae. Hepatitis B
      virus, hepatitis C virus (HCV), and anti-Helicobacter pylori antibodies were
      assessed by ELISA. In addition, sera were tested for a panel of antibodies
      associated with thrombophilia as well as various autoantibodies. Titers of
      antibodies toward HCV and T. gondii, and S. cerevisiae were higher in IBD
      patients than in controls, while the H. pylori autoantibodies were less prevalent
      among the patient population. Several thrombophilia-associated antibodies were
      more common in CD patients, and a single patient had a thromboembolic event. Our
      results show an excess of anti-HCV and anti-T. gondii antibodies among patients
      with IBD compared to healthy controls. Whereas the former may be the result of
      immunosuppression from the inflammatory disease itself or from the medications
      used to treat it, the latter association suggests that T. gondii is involved in
      the etiopathogenesis of IBD, and especially CD, in humans, as has been shown in
      the murine model. However, our findings also reiterate the positive association
      between CD and anti-S. cerevisiae antibodies as well as the negative association
      with H. pylori infections. These, in turn, lend indirect support to the "hygiene
      hypothesis" in IBD as well as the newly proposed role of commensal bacteria in
      the initiation of the disease process.

PMID- 19758211
TI  - Infectious serologies and autoantibodies in Wegener's granulomatosis and other
      vasculitides: novel associations disclosed using the Rad BioPlex 2200.
AB  - In this study we assess the presence of antibodies against infectious agents as
      well as for a variety of autoantibodies in an attempt to establish associations
      between various vasculitides and infections in order to shed light on the
      etiopathogenesis of these diseases and perhaps implicate a potential cure. Sera
      from patients with Wegener's granulomatosis (WG), polyarteritis nodosa,
      microscopic polyangiitis, Churg Strauss, and giant cell arteritis were compared
      to healthy control sera. Serum samples were assessed, using the Bio-Rad BioPlex
      2200, for the presence of Toxoplama gondii, cytomegalovirus (CMV), Epstein-Barr
      virus (EBV), Treponema pallidum, and Saccharomyces cerevisiae. Hepatitis B virus
      (HBV), hepatitis C virus (HCV), and anti-Helicobacter pylori antibodies were
      assessed by ELISA. In addition, sera were tested for a panel of antibodies
      associated with thrombophilia as well as various autoantibodies. The prevalence
      of antibodies toward HCV and H. pylori was significantly higher among patients
      with WG. IgG antibodies toward T. gondii and IgM antibodies toward CMV were
      significantly more common among WG patients than among controls. WG patients
      exhibited more antibodies toward EBV viral capsid antigen IgG and EBV early
      antigen IgG compared to sera from healthy controls. In WG, positive associations
      were disclosed between CMV IgG antibodies and the presence of gastrointestinal
      manifestations and renal involvement, and there was a higher Birmingham
      vasculitis activity score in association with elevated titers of EBV viral capsid
      antigen IgG antibodies. Otorhinolaryngeal manifestations were more common in
      those with positive IgG antibodies for EBV early antigen. Our results unveil
      novel associations between WG and various infectious agents, including HCV, H.
      pylori, T. gondii, CMV, and EBV. In addition to putative roles in initiation and
      exacerbation of the vasculitic process, it seems that these infectious agents
      also modulate the clinical phenotype of the disease.

PMID- 19758212
TI  - Exposure to Epstein-Barr virus infection is associated with mild systemic lupus
      erythematosus disease.
AB  - Infections may act as environmental triggers for the induction of systemic lupus
      erythematosus (SLE). In this study, we determine the relationship between disease
      manifestations of SLE patients and the titers of five Epstein-Barr virus (EBV)
      Abs. We evaluated the titers of early antigen IgG (EAG), nuclear antigen IgG,
      viral capsid antigen (VCA) IgG and IgM, and heterophile IgM, using the BioPlex
      2200 multiplexed immunoassay method in 260 sera (120 SLE patients and 140
      controls). EAG titers were significantly elevated (P < 0.024) in patients with
      cutaneous symptoms and increased anti-Ro antibody titers (P < 0.005). VCA IgG
      titers were significantly elevated (P < 0.003) in patients with joint
      involvement. None of the titers differed by central nervous system or renal
      involvement or antiphospholipid syndrome. We conclude that exposure to EBV
      infection may predict a disease phenotype of mild SLE disease with cutaneous and
      joint manifestations and elevated titers of anti-Ro Abs.

PMID- 19758213
TI  - Sugar-free antibodies--the bacterial solution to autoimmunity?
AB  - The enzyme EndoS from Streptococcus pyogenes is an immunomodulatory molecule
      hydrolyzing the conserved glycans in the effector part of immunoglobulin G (IgG).
      EndoS is remarkably specific for IgG, and hydrolysis has profound effects on IgG
      effector functions. EndoS pretreatment of IgG, or direct administration to
      animals with experimental antibody-mediated autoimmune diseases, inhibits
      development of disease or cures animals from established disease. The properties
      of EndoS make it a unique experimental tool and an attractive alternative to
      current therapies of conditions involving pathogenic antibodies. This review
      describes the discovery of EndoS, the effects of EndoS on IgG effector functions
      in vitro and in vivo, the biotechnological potential of EndoS, and the outcomes
      of EndoS treatment in animal models of autoimmunity.

PMID- 19758214
TI  - Infections may have a protective role in the etiopathogenesis of celiac disease.
AB  - Infectious agents have been implicated in the pathogenesis of many autoimmune
      diseases via various pathogenic mechanisms, such as molecular mimicry, resulting
      in modulation of the host's immune tolerance. In the following article we examine
      the association between serological evidence of past infection with Toxoplasma
      gondii, rubella virus, cytomegalovirus, Treponema pallidum, and Epstein-Barr
      virus, and the co-existence of celiac disease. Our results imply that certain
      infections may generate an immunological environment that disfavors future
      appearance of certain autoimmune conditions such as celiac disease.

PMID- 19758215
TI  - Antitreponemal antibodies leading to autoantibody production and protection from
      atherosclerosis in Kitavans from Papua New Guinea.
AB  - The objective of our study was to determine the prevalence of anti-infectious
      agent antibodies and autoantibodies in a unique non-Westernized population from
      Kitava, Papua New Guinea (PNG), compared to Western populations. We matched 120
      serum samples from Kitavans with 437 samples from four healthy control groups.
      Sera were tested for the presence of anti-infectious agent antibodies (treponema,
      toxoplsmosis, Epstein-Barr virus, cytomegalovirus, rubella) and autoantiobodies
      [anti-double-stranded (ds)DNA, anti-chromatin, anti-ribonucleoprotein (RNP), anti
      SSB, anti-SSA, anti-Scl-70, anti-Smith, anti-centromer, anti-SmRNP, anti-Jo-1,
      and anti-ribosomal-P] using the Bio-Rad BioPlex 2200. Antitreponemal antibodies
      were detected in 87% of PNG sera versus 0-6% of controls (P < 0.0001). Anti-dsDNA
      antibodies were detected in 31% of PNG samples, which was significantly higher
      than in three of the control groups (<10%). The outstanding high rate of
      antitreponemal antibodies detected in Kitavans possibly represents prior yaws
      disease. A low prevalence of cardiovascular disease was previously documented in
      Kitavans and has been attributed, in addition to their diet, to the high
      prevalence of natural cardioprotective autoantibodies (the IgM
      antiphosphorylcholine antibodies) in this population. Treponemal infection has
      been shown to induce the appearance of antiphosphorylcholine antibodies. These
      protective autoantibodies may cross-react with the pathogenic anti-dsDNA
      antibodies. Thus, it is suggested that infection with treponema is associated
      with the presence of protective as well as pathogenic autoantibodies.

PMID- 19758216
TI  - Rituximab in severe pemphigus.
AB  - Pemphigus is a life-threatening autoimmune bullous disorder that requires long
      term treatment with systemic corticosteroids mostly in conjunction with further
      immunosuppressants. Rituximab has opened a new avenue for severe and refractory
      pemphigus patients. In 95% of the 136 pemphigus patients reported to date in the
      English, French, and German literature, at least a partial remission has been
      achieved. In about two-thirds of communicated cases, application of rituximab
      resulted in the healing of all lesions. A controlled prospective study, however,
      has only recently being initiated. In pemphigus, rituximab is aimed at resetting
      the immune system to a condition in which autoreactive B lymphocytes are
      eliminated or sufficiently controlled. Here, we review mechanisms of action,
      different treatment protocols, clinical responses, and the safety profile of
      rituximab.

PMID- 19758217
TI  - Long-term effects of rituximab in rheumatoid arthritis: clinical, biologic, and
      pharmacogenetic aspects.
AB  - Rituximab selectively targets the B-cell compartment, including rheumatoid factor
      positive B cells. Short-term efficacy and safety of rituximab in rheumatoid
      arthritis (RA) has been established by multicenter randomized placebo-controlled
      studies. Results of long-term follow-up of the phase II/III clinical trials have
      confirmed the efficacy and safety of repeated courses of rituximab in the
      responders. However, mechanisms of action in humans, retreatment regimens,
      biologic effects on memory B cells and on immunoglobulin levels of prolonged
      exposure of the immune system to B-cell depletion over time, and pharmacogenetic
      aspects remain open and intriguing issues of rituximab therapy. Several studies
      are ongoing to clarify possible clinical and biologic predictors of response to
      rituximab in RA and in other autoimmune diseases where rituximab has been proven
      to be effective. Preliminary clinical and pharmacogenetic results of our cohort
      of RA patients managed with rituximab from the year 2000 are presented.

PMID- 19758218
TI  - Rituximab therapy in primary Sjogren's syndrome.
AB  - Primary Sjogren's syndrome is an autoimmune disease characterized by lymphocytic
      infiltration of glandular tissues leading to sicca symptoms, namely, dry eyes and
      dry mouth. In the majority of cases, the disease course is benign, albeit with
      considerable patient discomfort. Some patients, however, have systemic symptoms
      with arthritis, cutaneous vasculitis, low complement levels, and
      cryoglobulinemia. A small but not insignificant percentage of those patients
      evolve to B cell lymphoma. The increased expression of B cell survival factors,
      such as B cell activating factor, may promote the perpetuation of a B cell clone
      and precede the lymphoproliferative disease. Rituximab, a chimeric monoclonal
      antibody to CD20, leads to B cell depletion and may have a role in Sjogren
      systemic manifestations as well as in preventing and treating Sjogren-associated
      lymphoma.

PMID- 19758219
TI  - Role for CaMKII inhibition in rheumatoid arthritis: effects on HIF-1-induced VEGF
      production by rheumatoid synovial fibroblasts.
AB  - BACKGROUND AND AIMS: The present study was designed to investigate the effects of
      a novel CaMKII inhibitor SMP-114, which was effective in a collagen-induced
      arthritis model in rats, on rheumatoid synovial fibroblasts. METHODS: Rheumatoid
      synovial fibroblasts (RSF) were cultured under pro-inflammatory (IL-1beta
      stimulation) and hypoxic conditions. Protein and mRNA expression of HIF-1alpha
      and the effects of inhibitors of the CaMKII-, PI3K-, and ERK pathway on VEGF and
      IL-6 production were analyzed. RESULTS: Stimulation under hypoxic conditions
      induced higher expression of HIF-1alpha and VEGF mRNA than treatment with either
      IL-1beta or hypoxia alone. However, incubation with a specific CaMKII inhibitor
      did not result in reduced VEGF production in RSF. CONCLUSIONS: CaMKII activation
      has been reported to be involved in HIF-1alpha stabilization, but incubation with
      SMP-114, a specific CaMKII inhibitor, had no effect on HIF-1-induced VEGF
      production by rheumatoid synovial fibroblasts.

PMID- 19758220
TI  - Rituximab use in pediatric autoimmune diseases: four case reports.
AB  - Rituximab (RTX) is currently used in many diseases, but its efficacy and safety
      in juvenile systemic lupus erythematosus (SLEj) is still unknown. In this chapter
      we present four case reports of children treated with RTX: three SLE and one
      immune thrombocytopenic purpura (ITP). Two of the three SLEj patients had class
      IV lupus nephritis (LN) and hematologic manifestations (pancytopenia), both
      reaching complete recovery of blood counts and improvement of LN with RTX
      treatment. Our third SLE patient had a severe onset with generalized
      microangiopathic manifestations in association with antiphospholipid antibodies
      and has been in remission for almost 1 year after RTX. However, our fourth case,
      a patient with ITP and renal failure, was treated with RTX without either
      hematologic or renal response.

PMID- 19758221
TI  - Improvement of rituximab efficiency in chronic lymphocytic leukemia by CpG
      mediated upregulation of CD20 expression independently of PU.1.
AB  - Lipopolysaccharide (LPS), CpG-containing phosphothioate oligonucleotides (CpG)
      and various cytokines impact chronic lymphocytic leukemia (CLL) B cells. For
      example, they influence cell cycle entry, expression of co-receptors, and CD20.
      Rituximab (RTX), for which CD20 molecule is the target, proved to be less
      efficient in CLL than in lymphoma. This is accounted for by a lower CD20 level in
      the former than in the latter B lymphocytes. CD20 transcription is mediated by
      four transcription factors, of which only purine-rich box-1 (PU.1) is reduced in
      CLL. We thus examined the effects of LPS, CpG, tumor necrosis factor-alpha,
      interferon-alpha, interleukin (IL)-3, IL-4, IL-21, granulocyte macrophage-colony
      stimulating factor (CSF), and granulocyte-CSF on the transcription of PU.1, and
      the subsequent expression of CD20. It appeared that CpG was unique in that it
      raised the membrane expression of CD20 on malignant B cells, owing to a PU.1
      independent increase in its gene transcription. Moreover, RTX-induced complement
      mediated lysis was also ameliorated. Thus, CpG accelerates the transcription of
      CD20 independently of PU.1, and thereby improves the efficacy of RTX in CLL.

PMID- 19758222
TI  - B cell depletion in early rheumatoid arthritis: a new concept in therapeutics.
AB  - Rheumatoid arthritis is a severe, aggressive, and debilitating disease that has a
      high mortality rate. There have been considerable advances in the last few years
      as a result of developments in molecular biology, immunology, and biotechnology.
      The knowledge about the elements that directly participate in the genesis of the
      disease has been established. Nowadays, treatments are more rational and are
      directed to specific targets. Anticytokine agents, especially therapies that
      target tumor necrosis factor (TNF), are considered to be frontline biological
      agents for the treatment of rheumatoid arthritis. The blocking of lymphocyte B
      with rituximab, a genetically engineered chimerical monoclonal antibody, has been
      approved by the US Food and Drug Administration as a treatment in patients with
      rheumatoid arthritis who have severe disease not responding to conventional
      multiple therapies and to TNF-blocker agents. We propose that patients with
      severe aggressive rheumatoid arthritis could benefit from rituximab without
      previous exposure to anti-TNF agents as a biological agent, and we postulate that
      rituximab could be used as a first-line biological agent in this subgroup. We
      present our recent experience with patients having severe and active rheumatoid
      disease with whom we used rituximab as a first-line biological agent.

PMID- 19758223
TI  - Statins for the treatment of antiphospholipid syndrome?
AB  - Fluvastatin has been shown to revert proinflammatory/prothrombotic effects of
      antiphospholipid antibodies (aPL) in vitro and in mice. Here, we examined whether
      fluvastatin affects the levels of proinflammatory/prothrombotic markers in
      antiphospholipid syndrome (APS) patients. Vascular endothelial growth factor
      (VEGF), soluble tissue factor (sTF), tumor necrosis factor-alpha (TNF-alpha),
      soluble intercellular adhesion molecule-1 (sICAM-1), sE-selectin (E-sel), C
      reactive protein (CRP), and soluble vascular cell adhesion molecule (sVCAM-1),
      were measured in the sera of 93 APS patients and 60 controls and in the sera of
      nine patients with APS before and after 30 days of treatment with fluvastatin.
      Elevated levels of VEGF, sTF, and TNF-alpha were found in APS patients.
      Fluvastatin significantly reduced those markers in the majority of treated
      subjects. The data from this study show that statins may be beneficial in aPL
      positive patients and warrant larger clinical trials to confirm the efficacy of
      the drug for the treatment of APS clinical manifestations.

PMID- 19758224
TI  - Influence of statins on MHC class I expression.
AB  - Statins, inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase, are
      widely prescribed for their cholesterol-lowering properties to reduce
      atherogenesis and cardiovascular morbidity. However, compelling evidence exists
      that statins also have extensive immunomodulatory properties that operate
      independently of lipid lowering. Consequently, much attention has been directed
      toward their immunomodulatory effect and their potential as therapeutic agents
      for the treatment of autoimmune diseases. Statins have the ability to modulate a
      broad range of proinflammatory immune mechanisms through inhibition of small
      GTPases and other prenylated proteins. One of the statins' immunomodulatory
      effects is downregulation of MHC class II expression. In contrast, patients with
      statin-induced myopathy show high MHC class I expression. In this review, the
      effect of statins on MHC class I expression is reviewed alongside statins' effect
      on immune function.

PMID- 19758225
TI  - Proliferation signal inhibitors for the treatment of refractory autoimmune
      rheumatic diseases: a new therapeutic option.
AB  - Sirolimus and everolimus belong to the novel class of immunosuppressant agents
      known as proliferation signal inhibitors (PSIs). They act by preventing antigen
      driven T cell proliferation. While PSIs are widely used in transplantation, there
      are few reports of PSI usage in the treatment of autoimmune rheumatic diseases.
      The author has presented a series in the APLAR 2006 conference. This report
      summarizes the clinical experience with PSIs in the treatment of resistant or
      relapsed rheumatic diseases where conventional immunosuppressive agents have
      failed. This is a retrospective review of patients with various autoimmune
      rheumatic diseases who had sirolimus and everolimus treatment from the
      rheumatological clinics of Changi Hospital or the Arthritis and Rheumatism
      Specialist Medical Centre. The period of review was from April 2006 to April
      2008. A total of 46 patients were reviewed, 39 females and 7 males. The racial
      distribution was 33 Chinese, 7 Malays, and 6 Indians. Their disease conditions
      were as follows: 26 (57%) rheumatoid arthritis, 7 psoriatic arthritis, 4 systemic
      lupus erythematosus, 3 scleroderma, 2 anti-Jo-1 syndrome, 2 spondyloarthropathy,
      1 MCTD, and 1 vasculitis. All patients had failed at least three DMARDs or
      immunosuppressants. Twenty-eight patients received sirolimus and 28 patients
      received everolimus. Overall positive response rate was 48.2%. Twenty-seven
      percent had adverse events. 20% had no response. 7% relapsed after initial
      response. PSIs, namely sirolimus and everolimus, are a novel class of
      immunosuppressants that can be added to the armamentarium of rheumatologists for
      the treatment of patients with refractory autoimmune rheumatic diseases.

PMID- 19758226
TI  - Reversing bacteria-induced vitamin D receptor dysfunction is key to autoimmune
      disease.
AB  - Vitamin D research is discussed in light of the hypothesis that the lower average
      levels of vitamin D frequently observed in autoimmune disease are not a sign of
      deficiency. Instead, it is proposed that the lower levels result from chronic
      infection with intracellular bacteria that dysregulate vitamin D metabolism by
      causing vitamin D receptor (VDR) dysfunction within phagocytes. The VDR
      dysfunction causes a decline in innate immune function that causes susceptibility
      to additional infections that contribute to disease progression. Evidence has
      been accumulating that indicates that a number of autoimmune diseases can be
      reversed by gradually restoring VDR function with the VDR agonist olmesartan and
      subinhibitory dosages of certain bacteriostatic antibiotics. Diseases showing
      favorable responses to treatment so far include systemic lupus erythematosis,
      rheumatoid arthritis, scleroderma, sarcoidosis, Sjogren's syndrome, autoimmune
      thyroid disease, psoriasis, ankylosing spondylitis, Reiter's syndrome, type I and
      II diabetes mellitus, and uveitis. Disease reversal using this approach requires
      limitation of vitamin D in order to avoid contributing to dysfunction of nuclear
      receptors and subsequent negative consequences for immune and endocrine function.
      Immunopathological reactions accompanying bacterial cell death require a gradual
      elimination of pathogens over several years. Practical and theoretical
      implications are discussed, along with the compatibility of this model with
      current research.

PMID- 19758227
TI  - Colchicine revisited.
AB  - Purified from a Mediterranean plant nearly two centuries ago, colchicine has been
      discovered to inhibit many steps in the inflammatory process. The drug has good
      oral bioavailability and some enterohepatic recirculation, requiring dose
      adjustments for kidney disease and avoidance in liver disease. Toxicities are
      primarily gastrointestinal, hepatic, and hematologic. Colchicine is approved by
      the U.S. Federal Drug Administration for the treatment and prophylaxis of gout
      flares but has also been tried with varying success in the treatment of familial
      Mediterranean fever, primary biliary cirrhosis, psoriasis, Behcet's disease,
      aphthous stomatitis, linear IgA dermatosis, relapsing polychondritis, Sweet's
      syndrome, scleroderma, amyloidosis, leukocytoclastic vasculitis, epidermolysis
      bullosa, and dermatomyositis.

PMID- 19758228
TI  - A new bone marrow transplantation method for stem cell disorders.
AB  - Using animal models for autoimmune diseases, we have previously shown that
      allogeneic bone marrow transplantation (BMT) can be used to treat autoimmune
      diseases and that autoimmune diseases are hemopoietic stem cell (HSC) disorders.
      We have recently developed a new BMT method. The method consists of a perfusion
      method (PM) plus intrabone marrow (IBM)-BMT. The PM, in comparison with
      conventional aspiration, can minimize the contamination of BMCs with T cells from
      peripheral blood, and consequently no graft-versus-host disease develops. Because
      bone marrow cells collected by the PM contain not only HSCs but also mesenchymal
      stem cells (MSCs), the injection of both cells directly into the bone marrow
      cavity facilitates the engraftment of donor hemopoietic cells. Using this new
      method, we show that most age-associated diseases, such as osteoporosis and
      emphysema, are MSC disorders and, on the basis of this evidence, propose a new
      concept of stem cell disorders, including HSC and MSC disorders. We believe that
      the advent of IBM-BMT and our proposed concept herald a revolution in the field
      of transplantation (BMT and organ transplantation) and regeneration medicine.

PMID- 19758229
TI  - HE3286: a novel synthetic steroid as an oral treatment for autoimmune disease.
AB  - HE3286 (17alpha-ethynyl-5-androstene-3beta, 7beta, 17beta-triol) is a synthetic
      derivative of a natural anti-inflammatory steroid, beta-AET (5-androstene-3beta,
      7beta, 17beta-triol). HE3286 is orally bioavailable and treats established
      disease in models of ulcerative colitis, collagen-induced arthritis, and collagen
      antibody-induced arthritis, reducing clinical signs of disease and
      proinflammatory signals, including IL-6 and matrix metallopeptidase 3. HE3286
      modulates nuclear factor kappaB through an unknown mechanism but does not
      interact with any of the steroid-binding nuclear hormone receptors and is not
      immune suppressive. HE3286 was safe and well tolerated in phase I studies and is
      under evaluation in multicenter phase I/II clinical trials for ulcerative colitis
      and arthritis. HE3286 may provide a new treatment option for patients with
      inflammatory and autoimmune diseases.

PMID- 19758230
TI  - A fusion protein composed of IL-2 and caspase-3 ameliorates the outcome of
      experimental inflammatory colitis.
AB  - Targeted depletion of immune cells expressing the interleukin-2 (IL-2) receptor
      can exacerbate inflammatory bowel disease (IBD) through elimination of regulatory
      T (Treg) cells, or ameliorate its course by depletion of cytotoxic cells. To
      answer this question we used a fusion protein composed of IL-2 and caspase-3 (IL2
      cas) in an experimental model of DSS-induced toxic colitis. In a preventive
      setting, co-administration of DSS with a daily therapeutic dose of IL2-cas for
      seven days improved all disease parameters. Although CD4(+)CD25(+) T cells were
      depleted in the mesenteric lymph nodes, a fractional increase in CD4(+)FoxP3(+) T
      cells was observed in the spleen. Likewise, IL2-cas therapy improved the outcome
      of established disease in a chronic model of colitis. These data demonstrate that
      therapies that use IL-2 as a targeting moiety exert a protective effect over the
      colon under conditions of inflammation. The efficacy of IL-2-targeted therapy is
      attributed to reduced activity of reactive T cells, which ameliorates the
      secondary inflammatory infiltration. IL2-cas evolves as a potential therapeutic
      tool in IBD.

PMID- 19758231
TI  - Treatment of rat adjuvant arthritis with flavonoid (Detralex), methotrexate, and
      their combination.
AB  - In both adjuvant arthritis and rheumatoid arthritis, edema and inflammation
      appear in synovial joints. Edema or effusion reflects an imbalance in lymph
      dynamics. Purified micronized flavonoid fraction is mainly used in the treatment
      of chronic venous insufficiency. This compound improves lymphatic drainage with a
      significant increase in lymphatic flow and lymphatic pulsality. It is suggested
      that the beneficial effect of purified micronized flavonoid fraction may be
      involved in the treatment of adjuvant arthritis in rats. In this study treatment
      of adjuvant arthritis in rats with Detralex, methotrexate, and their combination
      were evaluated. Groups of rats with adjuvant arthritis were treated with
      methotrexate (0.6 mg/kg/week), Detralex (20 mg/kg/day), and their combination for
      50 days from adjuvant application. Hind paw swelling, arthrogram scores, serum
      albumin level, serum nitrite/nitrate concentrations, and whole-body mineral
      density were evaluated as markers of inflammation and destructive changes
      associated with arthritis. Long-term prophylactic treatment with low-dose
      methotrexate significantly inhibited the markers of both inflammation and
      arthritis. Detralex administered alone slightly decreased both the hind paw
      swelling and the arthritic score. Other inflammatory and arthritic markers were
      not significantly influenced. However, Detralex combined with methotrexate
      markedly potentiated the beneficial effects of methotrexate, which resulted in a
      more significant reduction in hind paw swelling, arthritic scores, and serum
      concentrations of nitrite/nitrate. Interestingly, the arthritis-induced decrease
      of bone mineral density in AA rats was significantly lower only in the group
      treated with the combination of Detralex and methotrexate. Our results indicate
      that Detralex increased the therapeutic efficacy of methotrexate basal treatment
      in AA. We suggest that this may be related to the beneficial effect of Detralex
      on microcirculation, especially on venules and lymphatic vessels.

PMID- 19758232
TI  - In vitro effects of antiphospholipid syndrome-IgG fractions and human monoclonal
      antiphospholipid IgG antibody on human umbilical vein endothelial cells and
      monocytes.
AB  - It has been shown that stimulation of endothelial cells and monocytes by
      antiphospholipid antibodies leads to a prothrombotic state involving upregulation
      of tissue factor (TF). We examined the in vitro effects of IgG fractions from
      patients with antiphospholipid syndrome (APS) and of a beta-2-glycoprotein 1
      independent human monoclonal antiphospholipid antibody (HL-5B) on human umbilical
      vein endothelial cells (HUVEC) in comparison to untreated cell controls and to
      exposure to monoclonal IgG control antibody. We also examined the effect of
      recombinant monocyte chemoattractant protein-1 (MCP-1) on peripheral blood
      monocytes. Stimulation of endothelial cells with APS IgG fractions or HL-5B
      resulted in time-dependent upregulation of MCP-1 mRNA and protein expression.
      Stimulation with HL-5B also led to time-dependent upregulation of interleukin
      (IL)-8 and intracellular adhesion molecule-1 (ICAM-1) mRNA and IL-8 protein
      expressions. Stimulation of monocytes with recombinant MCP-1 resulted in an
      upregulation of TF mRNA and TF protein. In conclusion these results might
      represent a mechanism for antiphospholipid antibody-mediated thrombosis in APS
      patients.

PMID- 19758233
TI  - Effects of biologics on vascular function and atherosclerosis associated with
      rheumatoid arthritis.
AB  - Endothelial dysfunction and accelerated atherosclerosis lead to increased
      cardiovascular morbidity and mortality in rheumatoid arthritis (RA). Sustained
      inflammation is a major risk factor. Apart from traditional vasculoprotective
      agents, biologics may also exert favorable effects on the vasculature. Indeed,
      tumor necrosis factor-alpha (TNF-alpha) inhibitors agents may transiently improve
      endothelial function. There are conflicting data regarding the effects of
      biologics on atherosclerosis and arterial stiffness. Infliximab stimulates the
      number and differentiation of endothelial progenitor cells that lead to vascular
      repair. There may be differences in the effects of TNF blockers on dyslipidemia,
      as long-term infliximab therapy may be proatherogenic, while some studies suggest
      that etanercept and adalimumab may exert beneficial effects on lipids. TNF
      blockers may decrease the incidence of cardiovascular events in RA. Preliminary
      data suggest that rituximab may also improve endothelial function and
      dyslipidemia. Further studies are needed to determine the net effects of
      biologics on the vasculature.

PMID- 19758234
TI  - Predictors of damage progression in Portuguese patients with systemic lupus
      erythematosus.
AB  - Patients with systemic lupus erythematosus (SLE) have a longer life expectancy.
      The occurrence of irreversible damage has become a major concern. The present
      study assessed damage progression in patients with SLE over a 2-year period and
      identified baseline features associated with damage accrual. Two hundred and
      twenty-one patients that fulfilled criteria for SLE and had a follow-up longer
      than 6 months were enrolled. Demographic, clinical, and immunological data were
      collected at baseline. Accumulated organ damage was scored using the Systemic
      Lupus International Collaborating Clinics/American College of Rheumatology damage
      index (SDI). Patients were prospectively followed and SDI assessment repeated at
      2 years. At baseline 72 patients (33%) presented some irreversible damage, and
      after 2 years 53 had accrued new damage. The mean SDI for the whole cohort
      increased from 0.582 to 0.980. Damage progression was higher in ocular,
      cardiovascular, and musculoskeletal systems. Older age [OR = 1.045; 95%
      confidence interval (CI) 1.021-1.069; P = 0.03], presence of antiphospholipid
      antibodies (OR = 3.047; 95% CI 1.169-7.941; P = 0.02), steroid use (OR = 6.401;
      95% CI 1.601-25.210; P = 0.008), azathioprine use (OR = 3.501; CI 1.224-10.012; P
      = 0.01), and hypertension (OR = 3.825; 95% CI 1.490-9.820; P = 0.005) were
      predictors of damage progression in multivariate analysis. Overall SDI increased
      over time, with some systems being affected more frequently. Demographic and
      clinical characteristics, co-morbidity, and treatment options may contribute to
      irreversible damage. It is necessary to determine whether the control of
      modifiable factors (e.g., hypertension and judicious use of medications) might
      prevent damage progression in SLE patients.

PMID- 19758235
TI  - An open-label study adding creatine monohydrate to ongoing medical regimens in
      patients with the fibromyalgia syndrome.
AB  - Fibromyalgia is an ill-defined condition that causes pain and disability but
      still lacks effective treatment. The aim of this open-label study was to assess
      the efficacy of administering a food supplement, creatine monohydrate, in an "add
      on" to existing therapies in patients with fibromyalgia. This study included 30
      patients with fibromyalgia. After 8 weeks of receiving creatine, we witnessed a
      significant improvement in parameters reflecting severity of fibromyalgia,
      quality of life and sleep, disability, and pain. These results deteriorated 4
      weeks after stopping creatine therapy. The findings of this study are preliminary
      and limited due to the small sample and relatively high rate of dropouts.

PMID- 19758236
TI  - TNF-alpha antagonist survival rate in a cohort of rheumatoid arthritis patients
      observed under conditions of standard clinical practice.
AB  - A cohort of rheumatoid arthritis (RA) patients in the Lombardy Rheumatology
      Network (LOHREN) registry and receiving anti-TNF therapy was evaluated after 6,
      12, 24, and 36 months. Of the 1114 patients in the registry 1064 met the clinical
      criteria for inclusion with 519 receiving infliximab, 303 adalimumab, and 242
      etanercept. The therapeutic survival curve of these patients showed that the
      likelihood of continuing anti-TNF therapy was 78.8% after 12 months, 65.2% after
      24 months, and 52.9% after 36 months, with a risk of dropout similar for
      inefficacy and adverse events. There were 405 anti-TNF therapy discontinuations
      (38.1%): 180 (16.9%) due to inefficacy, 194 (18.2%) adverse events, and 31 (2.9%)
      other reasons. Four deaths (2 septicemia, 1 postinfective cerebritis, 1 heart
      failure) were considered to be related to anti-TNF therapy. Of the
      discontinuations, 219 (54.1%) occurred within the first 12 months: 110 due to
      adverse events, 89 inefficacy, and 20 due to other reasons. After 36 months, the
      likelihood of survival on etanercept (62.5%) was significantly greater than the
      likelihood of survival on infliximab (49.1%) or adalimumab (53.6%). A higher risk
      of therapy discontinuations due to adverse events was associated with increasing
      age, a corticosteroid > 5 mg/day, a high erythrocyte sedimentation rate (ESR), a
      higher risk of therapy discontinuations due to inefficacy was associated with the
      previous use of > or = 4 disease-modifying antirheumatic drugs (DMARDs) and a
      high ESR. Comorbidities, increasing DAS28 values and co-therapy with methotrexate
      were associated with a lower risk of discontinuation.

PMID- 19758237
TI  - Treatment with PEG-interferon and ribavirin for chronic hepatitis C increases
      neutrophil and monocyte chemotaxis.
AB  - The incidence of infections increases during treatment with pegylated interferon
      (PEG-IFN) and ribavirin (RBV) for chronic hepatitis C (CHC). Despite a reduction
      in neutrophil count, there is no clear relationship between infection occurrence
      and neutropenia. In the present study we investigated whether HCV treatment
      alters leukocyte function. We studied cell chemotaxis, reactive oxygen species,
      neutrophil phagocytosis, CR3 expression, and plasma colony stimulating factors
      (CSF) in 20 healthy subjects and 20 patients with CHC (10 with cirrhosis) at
      baseline, during antiviral treatment (at 4, 12, 24 weeks), and 12 weeks after
      discontinuation. Our results demonstrate that neutrophil chemotaxis and oxidative
      burst significantly increased during treatment and returned to baseline at the
      end of therapy. CR3 neutrophil expression was enhanced in baseline CHC compared
      to controls but did not change during antiviral treatment. Chemotaxis, oxidative
      burst, phagocytosis, and CSF levels did not differ significantly between patients
      before treatment and control subjects or among CHC cases according to the
      presence of cirrhosis in either cell subpopulation. In conclusion, the innate
      immune cell activity is enhanced in patients with CHC during antiviral treatment
      and returns to normal after its discontinuation thus possibly playing a role in
      their susceptibility to infections.

PMID- 19758238
TI  - CpG ODN enhances the efficacy of rituximab in non-Hodgkin lymphoma.
AB  - The anti-CD20 monoclonal antibody rituximab (RTX) has been applied to the therapy
      of B-cell proliferative disease, but a number of factors, such as the expression
      level of its target antigen, modulate its efficacy. Since unmethylated CpG
      containing DNA sequences activate members of the immune systems, including B
      lymphocytes, their benefit to RTX treatment was determined on human lymphoma B
      cell line cells. These Daudi cells expressed high endosomal level of the CpG Toll
      like receptor 9, but CpG had effects neither on the viability, nor on the
      proliferation of the cells. In contrast, there appeared to be an increase in the
      expression of CD20, resulting in a higher efficiency of RTX for the killing of
      malignant Daudi cells.

PMID- 19758239
TI  - Enhancing the action of rituximab in chronic lymphocytic leukemia by adding fresh
      frozen plasma: complement/rituximab interactions & clinical results in refractory
      CLL.
AB  - Many patients with chronic lymphocytic leukemia (CLL) develop progressive
      treatment-resistant disease. Rituximab (RTX), a monoclonal antibody targeting
      CD20 on B lymphocytes and widely used in other indolent B-cell neoplasms is less
      efficacious in CLL, possibly because of associated complement deficiencies.
      Initial in vitro and in vivo observations support the central role of complement
      in rituximab-mediated loss of CD20(+) cells in CLL. In an open trial conducted in
      outpatient hematology clinics in Israel and Greece, we examined whether providing
      complement by concurrent administration of fresh frozen plasma (FFP) would
      enhance the effect of RTX in CLL. Five patients with severe treatment-resistant
      CLL were included in the trial. All had been previously treated with fludarabine,
      and three also failed treatment with RTX. Each patient was treated with two units
      of FFP followed with RTX 375 mg/m(2) as a single agent, repeated every 1-2 weeks
      as needed. A rapid and dramatic clinical and laboratory response was achieved in
      all patients. Lymphocyte counts dropped markedly followed by shrinkage of lymph
      nodes and spleen and improvement of the anemia and thrombocytopenia. This could
      be maintained over 8 months (median) with additional cycles if necessary.
      Treatment was well tolerated in all cases. In conclusion, adding FFP to RTX may
      provide a useful therapeutic option in patients with advanced CLL resistant to
      treatment. Further studies are needed to confirm and study the efficacy of the
      FFP/RTX combination in advanced CLL, establish the mechanisms, and possibly
      extend its use to other B-cell-dependent pathologies, such as treatment
      refractory autoimmune diseases.

PMID- 19758240
TI  - Effects of low-molecular-weight heparin on adhesion and vesiculation of
      phospholipid membranes: a possible mechanism for the treatment of
      hypercoagulability in antiphospholipid syndrome.
AB  - Heparins represent an efficient treatment of acute thrombosis and obstetric
      complications in antiphospholipid syndrome (APS). Enhanced microvesiculation of
      cell membranes, as detected by reduced membrane adhesion, can contribute to
      hypercoagulability in APS. Healthy donor IgG antibodies significantly increased
      beta2-glycoprotein I (beta2-GPI)-induced membrane adhesion, indicating that IgG
      antibodies might supplement the role of beta2-GPI in the regulation of membrane
      microvesiculation in healthy individuals. Anti-beta2-GPI IgG antibodies
      significantly reduced beta2-GPI-induced membrane adhesion, suggesting a direct
      role of anti-beta2-GPI antibodies in enhancing membrane microvesiculation in APS.
      Therapeutic concentration of nadroparin completely restored beta2-GPI-induced
      membrane adhesion in the presence of anti-beta2-GPI IgG antibodies. A novel
      anticoagulant mechanism of nadroparin in APS is suggested that supplements its
      direct effect on the coagulation cascade. Restoration of adhesion between
      negatively charged membranes in the presence of nadroparin might decrease
      shedding of microvesicles into the surrounding solution and could thus contribute
      to the efficacy of heparin treatment in APS.

PMID- 19758241
TI  - Phenotypic heterogeneity in expression of epitopes in the Cryptococcus neoformans
      capsule.
AB  - The opportunistic yeast Cryptococcus neoformans is surrounded by a polysaccharide
      capsule comprised primarily of glucuronoxylomannan (GXM). GXM is a key component
      of the antigenic character of the capsule. Expression of the epitope that allows
      for binding of mAbs that require O-acetylation of GXM for mAb recognition was
      greatly influenced by cell age, growth conditions and serotype. Yeast cells of
      serotype A grown in vitro under capsule induction conditions showed considerable
      cell-to-cell variability in binding of two O-acetyl-dependent mAbs, and such mAbs
      uniformly failed to bind to GXM that covers yeast buds. Expression of the O
      acetyl-dependent epitope increased with cell age. In contrast, all serotype A
      cells harvested from brain tissue bound the same O-acetyl-dependent mAbs. The
      ability of the cryptococcal capsule to activate the complement cascade and bind
      C3 occurred uniformly over the surface of all yeast cells, including the bud.
      Finally, the cell-to-cell variability in binding of O-acetyl-dependent mAbs with
      strains of serotype A was not found with strains of serotype D; almost all cells
      of serotype D showed homogeneous binding of O-acetyl-dependent mAbs. These
      results indicate that variability in expression of antigenic epitopes by GXM
      should be considered in selection of mAbs used for immunodiagnosis or
      immunotherapy.

PMID- 19758242
TI  - Model specification in oral health-related quality of life research.
AB  - The aim of this study was to analyze conventional wisdom regarding the
      construction and analysis of oral health-related quality of life (OHRQoL)
      questionnaires and to outline statistical complications. Most methods used for
      developing and analyzing questionnaires, such as factor analysis and Cronbach's
      alpha, presume psychological constructs to be latent, inferring a reflective
      measurement model with the underlying assumption of local independence. Local
      independence implies that the latent variable explains why the variables observed
      are related. Many OHRQoL questionnaires are analyzed as if they were based on a
      reflective measurement model; local independence is thus assumed. This assumption
      requires these questionnaires to consist solely of items that reflect, instead of
      determine, OHRQoL. The tenability of this assumption is the main topic of the
      present study. It is argued that OHRQoL questionnaires are a mix of both a
      formative measurement model and a reflective measurement model, thus violating
      the assumption of local independence. The implications are discussed.

PMID- 19758243
TI  - Consequences for enamel development and mineralization resulting from loss of
      function of ameloblastin or enamelin.
AB  - Although the nonamelogenin proteins, ameloblastin and enamelin, are both low
      abundance and rapidly degrading components of forming enamel, they seem to serve
      essential developmental functions, as suggested by findings that an enamel layer
      fails to appear on teeth of mice genetically engineered to produce either a
      truncated form of ameloblastin (exons 5 and 6 deleted) or no enamelin at all
      (null). The purpose of this study was to characterize, by direct micro weighing,
      changes in enamel mineralization occurring on maxillary and mandibular incisors
      of mice bred for these alterations in nonamelogenin function (Ambn(+/+, +/-5,6, 
      5,6/-5,6), Enam(+/+, +/- ,-/-)). The results indicated similar changes to enamel
      mineralization patterns within the altered genotypes, including significant
      decreases by as much as 50% in the mineral content of maturing enamel from
      heterozygous mice and the formation of a thin, crusty, and disorganized
      mineralized layer, rather than true enamel, on the labial (occlusal) surfaces of
      incisors and molars along with ectopic calcifications within enamel organ cells
      in Ambn(-5,6/-5,6) and Enam(-/-) homozygous mice. These findings confirm that
      both ameloblastin and enamelin are required by ameloblasts to create an enamel
      layer by appositional growth as well as to assist in achieving its unique high
      level of mineralization.

PMID- 19758244
TI  - Functional estrogen receptors alpha and beta are expressed in normal human
      salivary gland epithelium and apparently mediate immunomodulatory effects.
AB  - Salivary gland epithelial cells (SGECs) have been shown to participate in
      immunological responses and have been implicated in the pathogenesis of Sjogren's
      syndrome (SS). Experimental evidence from animal models indicates that estrogen
      deficiency may also participate in SS pathogenesis. However, the expression and
      functionality of the estrogen receptors alpha (ERalpha) and beta (ERbeta) in
      normal human salivary epithelium is unknown. To investigate these points,
      formalin-fixed, paraffin-embedded specimens and cultured non-neoplastic SGEC
      lines derived from nine minor salivary gland (MSG) biopsies with normal histology
      were studied. Immunohistochemical analyses detected the epithelial expression of
      ERalpha, ERbeta1, and ERbeta2 protein isoforms both in MSG tissues and in
      cultured SGECs. Such epithelial expression was verified by immunoblotting of
      various ER proteins in cellular extracts of cultured SGECs (full-length-ERalpha,
      ERalpha-Delta3, ERbeta1-long, ERbeta1-short, and ERbeta2-long isoforms).
      Estrogens did not induce growth or apoptosis in cultured SGECs. However,
      similarly to other cellular systems, treatment of cultured SGECs with estrogens
      (17beta-estradiol and the ERalpha- and ERbeta-selective agonists propylpyrazole
      triol and diarylpropiolnitrile, respectively) inhibited the interferon-gamma
      inducible expression of intercellular adhesion molecule-1. This finding
      corroborated the functionality of ER expressed by SGEC. Our results suggest that
      salivary epithelium expresses constitutively functional ERalpha and ERbeta
      proteins that apparently mediate immunomodulatory effects.

PMID- 19758245
TI  - Localization of antimicrobial peptides human beta-defensins in minor salivary
      glands with Sjogren's syndrome.
AB  - Sjogren's syndrome is a common systemic autoimmune disease associated with
      inflammatory cells that infiltrate exocrine glands. The antimicrobial peptides
      human beta-defensin-1, human beta-defensin-2, and human beta-defensin-3 are
      expressed in various human epithelial cells and in normal salivary glands.
      Antimicrobial peptides provide local protection against infection and participate
      in inflammatory responses. Because of the presence of inflammation, we
      hypothesized that human beta-defensin expression in minor salivary glands may be
      increased in subjects with Sjogren's syndrome. However, the expression of human
      beta-defensins 1 and 2 was decreased in salivary glands affected by Sjogren's
      syndrome in comparison with the human beta-defensin expression patterns in
      salivary glands from normal subjects. In addition, the reduction in expression of
      human beta-defensin-2 was greater than the reduction in expression of human beta
      defensin-1. The aforementioned result suggests that the reduction in expression
      of human beta-defensin-2 may occur earlier than the reduction in expression of
      human beta-defensin-1, which may lead to a greater decrease in human beta
      defensin-2 than in human beta-defensin-1 during disease progression.

PMID- 19758246
TI  - Signal transduction and gene transcription induced by TFF3 in oral keratinocytes.
AB  - Trefoil factor family 3 (TFF3) is secreted in saliva. The peptide improves the
      mechanical and chemical resistance of mucins, and it may act as a motility signal
      for oral keratinocytes during wound healing. This study aimed to identify novel
      functions of TFF3 in oral keratinocytes. To achieve this, we used phosphoprotein
      and messenger RNA (mRNA) arrays to compare TFF3-treated and untreated oral
      keratinocytes. Analysis of the phosphoprotein array indicated that TFF3 signals
      through the mitogen-activated protein kinases (MAPKs) c-Jun N-terminal kinase
      (JNK), p38, and extracellular signal-regulated kinase (ERK1/2), and through the
      phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB) pathway. Microarray
      analysis of mRNA showed that TFF3 stimulation induced changes in the expression
      of genes functionally related to cell death/survival, cell growth and
      proliferation, and cell movement. The reverse transcription-polymerase chain
      reaction (RT-PCR) results indicated that the transcription of some immediate
      early genes (IEGs) was downregulated, whereas the IEGs FBJ osteosarkoma oncogene
      (FOS) and C-MYC binding protein (MYCBP2) were transiently upregulated by TFF3
      stimulation. Together, the results of the arrays indicate that TFF3 is a
      modifying factor in pathways regulating cell survival, cell growth and
      proliferation, and cell migration of oral keratinocytes. Trefoil factor family 3
      may therefore promote oral wound healing and it should be considered for the
      treatment of oral ulcerating diseases, or of other diseases.

PMID- 19758247
TI  - Localization and potential function of kindlin-1 in periodontal tissues.
AB  - Kindlin-1 is an intracellular focal adhesion protein that regulates the actin
      cytoskeleton. Patients suffering from Kindler syndrome have a homologous mutation
      of the kindlin-1 gene and develop skin blisters, periodontal disease, and
      intestinal complications because of deficient adhesion of the basal epithelial
      cells. We investigated kindlin-1 localization in periodontal tissue and its
      functions in cultured keratinocytes and showed that kindlin-1 co-localizes with
      migfilin and paxillin in the basal epithelial cells of oral mucosa and in
      cultured keratinocytes. The kindlin-1-deficient oral mucosal tissue from a
      patient with Kindler syndrome showed a complete lack of paxillin and reduced
      migfilin immunostaining in the basal keratinocytes. Co-immunoprecipitation showed
      that migfilin directly interacted with kindlin-1. RNA interference-induced
      kindlin-1 deficiency in keratinocytes led to an altered distribution of migfilin
      containing focal adhesions, reduced cell spreading, decreased cell proliferation,
      and decelerated cell migration. Disruption of microtubules in the kindlin-1
      deficient cells further reduced cell spreading, suggesting that microtubules can
      partially compensate for kindlin-1 deficiency. Kindlin-1 supported mature cell
      extracellular matrix adhesions of keratinocytes, as downregulation of kindlin-1
      expression significantly reduced the cell-adhesion strength. In summary, kindlin
      1 interacts with migfilin and plays a crucial role in actin-dependent
      keratinocyte cell adhesion essential for epidermal and periodontal health.

PMID- 19758248
TI  - Epidermal growth factor-induced cyclooxygenase-2 expression in oral squamous cell
      carcinoma cell lines is mediated through extracellular signal-regulated kinase
      1/2 and p38 but is Src and nuclear factor-kappa B independent.
AB  - The intracellular signalling cascade(s) mediating epidermal growth factor (EGF)
      induced cyclooxygenase-2 (COX-2) expression is poorly defined in oral carcinomas.
      Investigation of two different oral squamous cell carcinoma (OSCC) cell lines
      with high EGF-induced COX-2 expression revealed, however, that this expression
      was dependent on two mitogen-activated protein kinase (MAPK) pathways
      [extracellular signal-regulated kinase 1/2 (ERK1/2) and p38] because combined
      inhibition of these pathways was needed to abolish EGF-induced COX-2 expression.
      Surprisingly, inhibition of phosphoinositide-3 kinase (PI3K) increased EGF
      induced COX-2 expression in the basaloid OSCC cell line (C12), suggesting a PI3K
      controlled, inhibitory COX-2-regulating pathway. Neither the transcription factor
      nuclear factor-kappaB (NF-kappaB), nor Src, was involved in EGF-induced COX-2
      expression. The results suggest that EGF-induced COX-2 expression is regulated by
      several pathways, and emphasizes that individual tumors use different strategies
      for intracellular signalling.

PMID- 19758249
TI  - Epstein-Barr virus prevalence in oral squamous cell cancer and in potentially
      malignant oral disorders in an eastern Hungarian population.
AB  - We tested 65, 44, and 116 patients with oral squamous cell cancer (OSCC), oral
      leukoplakia (OL), and oral lichen planus (OLP) against 68 age-matched controls
      for the presence of Epstein-Barr virus (EBV). Apparently healthy mucosa was
      simultaneously sampled and examined in all patients. Paraffin-embedded tissue
      sections of all EBV-positive patients with OSCC were examined for latent membrane
      protein-1 (LMP-1) expression (demonstrable in most EBV-associated malignancies)
      using immunohistochemistry. The prevalence of EBV in the controls and in OSCC,
      OL, and OLP lesions was 19.1%, 73.8%, 29.5%, and 46.6%, respectively, and 66.2%,
      22.7%, and 31.9% in the healthy mucosa of patients, respectively. The prevalence
      of EBV in OSCC patients was significantly higher than in controls or in
      respective samples of the other two patient groups both in the lesion and in the
      healthy mucosa. Comparisons including only patients with EBV-negative lesions
      yielded similar results. Lesions of patients with OLP, but not of patients with
      OL, differed significantly from controls in EBV prevalence. In OSCC, LMP-1
      expression was not detected, and EBV carriage was not significantly associated
      with any risk factors and did not influence the outcome. Although a high
      prevalence of EBV was found in OSCC, comparable carriage rates on healthy mucosa
      of patients indicated that an aetiological role of EBV is unlikely.

PMID- 19758250
TI  - Is diagnostic delay related to advanced-stage oral cancer? A meta-analysis.
AB  - Diagnostic delay in oropharyngeal cancer may be associated with poor prognosis.
      As controversy exists on this topic because of contradictory results, the aim of
      this study was to perform a systematic review of the relationship between total
      diagnostic delay and advanced disease stages. A systematic search of MEDLINE,
      EMBASE, and ISI proceedings was made to identify observational studies that
      provided relative risks (RRs) and 95% confidence intervals (CIs) for patients
      with confirmed pathological diagnosis. The outcome of interest was disease stage
      (TNM classification), while the exposure of interest was the total diagnostic
      delay. The study-specific adjusted log RRs for cohort studies were weighted by
      the inverse of their variance to compute a pooled RR and its 95% CI. The fixed
      effects pooled RR of advanced stages of oropharyngeal cancer when diagnostic
      delay is present was 1.32 (95% CI: 1.07-1.62). This association was stronger when
      the analysis was restricted to oral cancer (pooled RR: 1.47; 95% CI: 1.09-1.99)
      and when delay was longer than 1 month (pooled RR: 1.69; 95% CI: 1.26-2.77). The
      probability for patients with delayed diagnosis to present an advanced-stage
      tumour at diagnosis was significantly higher than that of patients with no delay
      in diagnosis. However, new prospective studies with strict methodology are needed
      to shed more light on this association.

PMID- 19758251
TI  - Contextual effects in the occurrence of periodontal attachment loss and
      necrotizing gingival lesions among adolescents.
AB  - The aim of this study was to assess and quantify the random effects resulting
      from clustering in the following individual-level periodontal outcomes: presence
      of clinical attachment loss of > or = 1 mm (CAL1), presence of clinical
      attachment loss of > or = 3 mm (CAL3), and presence of necrotizing ulcerative
      gingivitis (NUG); or in the following class-level periodontal outcomes: number of
      students with CAL1, number of students with CAL3, and number of students with
      NUG. Mixed-effects logistic regression analysis was used to model these outcomes
      among 9,162 adolescents in 310 classes in 98 schools spread over 20 communes in
      the Province of Santiago, Chile, who had been examined for clinical attachment
      level and NUG, and had completed questionnaires on oral health-related behaviors.
      The results of all six analyses demonstrated statistically significant random
      effects, which in all analyses were particularly related to the schools, whereas
      the class effects were smaller and the commune random effects were almost
      negligible. The random effects were quantified using the median odds ratio (MOR),
      and the class-level MOR ranged between 1.05 and 1.51, whereas the school-level
      MOR values ranged from 2.07 to 2.39. The results of the study demonstrate the
      potential of the application of multilevel modeling to periodontal epidemiologic
      data, over and beyond the conventional use of the technique to account for the
      intrinsic sites-teeth-subject hierarchy in periodontal data.

PMID- 19758252
TI  - Nitration of the salivary component 4-hydroxyphenylacetic acid in the human oral
      cavity: enhancement of nitration under acidic conditions.
AB  - 4-Hydroxyphenylacetic acid (HPA) and nitrite are present in human mixed whole
      saliva, and HPA can be nitrated by peroxidase/hydrogen peroxide
      (H(2)O(2))/nitrite systems in the oral cavity. Thus, the objectives of the
      present study were to estimate the concentrations of HPA, nitrated HPA [4-hydroxy
      3-nitrophenylacetic acid (NO(2)HPA)], nitrite, and thiocyanate (SCN(-)) in saliva
      from 73 patients with periodontal diseases and to elucidate the conditions
      necessary to induce nitration of HPA. High concentrations of HPA, nitrite, and
      SCN(-) were found in the saliva of patients older than 50 yr of age. NO(2)HPA was
      detected in seven patients who were older than 60 yr of age. Nitrite-dependent
      formation of NO(2)HPA by a bacterial fraction prepared from mixed whole saliva
      was faster at pH 5.3 than at pH 7, and increased as the rate of H(2)O(2)
      formation increased. The formation of NO(2)HPA was inhibited by SCN(-) and by
      salivary antioxidants such as uric acid, ascorbic acid, and glutathione. These
      results suggest that nitration can proceed at an acidic site in the oral cavity
      where H(2)O(2) is produced under conditions of decreased concentrations of SCN(-)
      and of antioxidants.

PMID- 19758253
TI  - Effect on de novo plaque formation of rinsing with toothpaste slurries and water
      solutions with a high fluoride concentration (5,000 ppm).
AB  - The aim of this study was to evaluate the effect, on de novo plaque formation, of
      rinsing with toothpaste slurries and water solutions containing a high
      concentration of fluoride (F). Sixteen subjects rinsed three times per day for 4
      d with dentifrice slurries containing 5,000, 1,500, and 500 ppm F, while 12
      subjects rinsed with water solutions containing 5,000, 1,500, 500, and 0 ppm F,
      and 1.5% sodium lauryl sulphate (SLS). Plaque was scored [using the Quigley &
      Hein index (QHI)] after each 4-d period. Plaque samples for F analysis were
      collected. Significantly less plaque was scored for the dentifrice slurry
      containing 5,000 ppm F (buccal and all surfaces) and for 1.5% SLS (buccal
      surfaces). The differences in plaque scores between dentifrice containing 5,000
      and 1,500 ppm F were 19% for all surfaces and 33% for buccal surfaces. The
      difference between the water solutions containing 1.5% SLS and 1,500 ppm F for
      buccal surfaces was 23%; the corresponding difference for 5,000 ppm F was 17%.
      The dentifrice slurry containing 5,000 ppm F accumulated 56% more F in plaque.
      The combination of high levels of F and SLS in dentifrice reduces de novo plaque
      formation and increases the accumulation of F in plaque after 4 d.

PMID- 19758254
TI  - Evaluation of the antimicrobial effect of photodynamic antimicrobial therapy in
      an in situ model of dentine caries.
AB  - Photodynamic antimicrobial therapy (PACT) promotes bacterial death as a result of
      the photosensitization of microbial components. This study evaluated the effect
      of PACT on dentine caries produced in situ. Over the course of 14 d, 20
      volunteers wore intra-oral devices containing human dentine slabs that were
      treated 10 times daily with a 40% sucrose solution. Afterwards, the antimicrobial
      effect of toluidine blue O, associated with 47 or 94 J cm(-2) of a light-emitting
      diode, was evaluated. Before and after the treatments, dentine samples were
      analysed with regard to the total number of microorganisms, total streptococci,
      mutans streptococci, and lactobacilli. Significant reductions in the bacterial
      count were observed for PACT with both energy densities tested, with the
      following values observed for 47 and 94 J cm(-2) of irradiation: for total
      streptococci, 3.45 and 5.18; for mutans streptococci, 3.08 and 4.16; for
      lactobacilli, 3.24 and 4.66; and for total microorganisms, 4.29 and 5.43,
      respectively. The control, treated with 94 J cm(-2) of irradiation alone, was
      also effective against all bacteria. To conclude, PACT was effective in killing
      oral microorganisms present in dentine caries produced in situ and may be a
      useful technique for eliminating bacteria from dentine carious lesions before
      restoration.

PMID- 19758255
TI  - Long-term effect of an oral healthcare programme on oral hygiene in a nursing
      home.
AB  - This article reports on the long-term effect of an oral healthcare programme
      aimed at improving and maintaining the oral hygiene of elderly residents in a
      nursing home. The method was based on (i) motivation and oral-care training of
      the nursing staff, (ii) production of picture-based oral-care procedure cards,
      (iii) distribution of adequate oral-care equipment, (iv) practical implementation
      of new routines, and (v) assessment of results attained. The level of oral
      hygiene in the nursing home was assessed using the mucosal-plaque score (MPS)
      index. Overall evaluation was made before the start of the study, after 3 months,
      and eventually after 6 yr. Before implementation of the oral healthcare
      programme, 36% of the residents had an acceptable score. Six years later, the
      proportion was 70%. The evaluation showed that the introduction of such an oral
      healthcare programme significantly improved the oral hygiene of the residents on
      a long-term basis. However, 30% of the residents did not achieve an acceptable
      score because they were very ill or dying, aggressive or wanted to brush their
      teeth themselves.

PMID- 19758256
TI  - Mixing ability test compared with a comminution test in persons with normal and
      compromised masticatory performance.
AB  - A mastication test was needed with a material that forms a bolus and is soft
      enough to be chewed by persons with compromised oral function, in particular
      patients confronted with oral cancer. We therefore developed a wax-mixing ability
      test and compared it with a comminution test using Optocal as test food. We
      hypothesized that the mixing ability test would be better at differentiating
      between groups of persons with compromised masticatory performance than the
      comminution test. Sixty healthy subjects were recruited in three groups of 20,
      matched for age and gender: a group with natural dentition; a group with full
      dentures; and a group with maxillary denture and implant-supported mandibular
      overdenture. The mixing ability test was found to discriminate better between the
      two full-denture groups than the comminution test.

PMID- 19758257
TI  - Influence of chlorhexidine digluconate concentration and application time on
      resin-dentin bond strength durability.
AB  - Although it is known that chlorhexidine application may preserve resin-dentin
      bonds from degradation, the lowest optimal concentration and application time
      have yet to be established. This study evaluated the effects of different
      concentrations of chlorhexidine digluconate and different application times on
      the preservation of resin-dentin bonds formed using two etch-and-rinse adhesives.
      In experiment 1, after acid etching, the occlusal demineralized dentin was
      rewetted either with water or with 0.002, 0.02, 0.2, 2, or 4% chlorhexidine for
      60 s. In experiment 2, the surfaces were rewetted with water, or with 0.002% or
      2% chlorhexidine for 15 or 60 s. After this, both adhesives and composite resin
      were applied and light-cured. Bonded sticks (0.8 mm(2)) were tested under tension
      (0.5 mm min(-1)) immediately or after 6 months of storage in water. Two bonded
      sticks from each tooth were immersed in silver nitrate and analyzed
      quantitatively using scanning electron microscopy. Reductions in microtensile
      bond strengths and higher silver nitrate uptake were observed for both adhesives
      when the rewetting procedure was performed with water. Stable bonds were
      maintained for up to 6 months under all chlorhexidine conditions tested,
      irrespective of the chlorhexidine concentration and application time. The use of
      0.002% chlorhexidine for 15 s seems to be sufficient to preserve resin-dentin
      interfaces over a 6-month period.

PMID- 19758258
TI  - Does endodontic post space irrigation affect smear layer removal and bonding
      effectiveness?
AB  - The effect of different post space irrigants on smear layer removal and dentin
      bond strength was evaluated. Sixty-six extracted sound maxillary central incisors
      were endodontically treated. After post space preparation, the teeth were
      assigned to three groups of 22 teeth each. The teeth of these three groups were
      irrigated for 1 min with 17% ethylenediaminetetracetic acid (EDTA) (group 1),
      5.25% sodium hypochlorite (NaOCl) (group 2), or 0.9% sodium chloride (NaCl)
      (group 3). In each group, eight specimens were split longitudinally for smear
      layer evaluation, and the other fourteen specimens were filled with a self
      etching adhesive system (Panavia F). Four of 14 specimens of each group were
      prepared for evaluation of the resin-dentin interdiffusion zone (RDIZ) and resin
      tags, and the other 10 specimens were serially sectioned for push-out test
      analysis. Smear layer removal and bond strength were affected by different post
      space irrigants. EDTA removed the smear layer extremely effectively and, as a
      result, improved the bond strength at each region (apical, middle, and coronal)
      of the roots. Resin tag formation and the RDIZ were also affected by different
      irrigants and in accordance with bond strength. Therefore, removal of the smear
      layer use a self-etching luting system plays an important role in bonding
      effectiveness.

PMID- 19758259
TI  - Effectiveness of bonding fiber posts to root canals and composite core build-ups.
AB  - This study investigated the effects of fiber posts, silanization, and luting
      agents on the interfacial strength to root dentin and composite cores. Root
      canals of 120 crownless human teeth were instrumented. Three different posts
      (opaque and translucent), with and without silane treatment, were bonded using
      etch-and-rinse, self-etch, and self-adhesive luting agents. The restored roots
      were built up with dual-curing composite. After storage in water for 24 h at 37
      degrees C, 2-mm-thick slices were cut from each sample: one from the composite
      core and one from the restored root. Interfacial push-out bond strengths of the
      posts were determined in a universal testing machine. Failure modes were analyzed
      using scanning electron microscopy. The post type and the luting agent had
      significant effects on both the post-to-dentin and post-to-core strengths.
      Silanization did not significantly influence post-to-dentin strengths, but
      enhanced post-to-core strengths. With etch-and-rinse luting agents, debonding
      occurred predominantly between the post and the cement, while the self-etch and
      self-adhesive luting agents showed more failures on root dentin. No failures
      occurred between the composite core and the cement. The combination of
      translucent posts and etch-and-rinse dual-curing luting agents can positively
      influence the retention of fiber posts in root canals. Silanization seems to be
      less relevant for intra-root canal bonding, but may have beneficial effects on
      post-to-core strengths.

PMID- 19758260
TI  - In vitro degradation of resin-dentin bonds with one-bottle self-etching
      adhesives.
AB  - The purpose of this study was to evaluate the durability of one-bottle self
      etching adhesive during long-term water-storage testing. Resin-dentin bonded
      specimens were prepared using four commercially available one-bottle self-etching
      adhesives. The specimens were sectioned perpendicular to the adhesive interface
      to produce beam-shaped specimens that were stored in water for 24 h (control
      group) and 100, 200, and 300 d (experimental groups). After each storage period,
      the beams were subjected to a microtensile bond test. After the bond test,
      fractured surfaces were examined using a scanning electron microscope. In
      addition, interfacial observations of the silver tracer were performed using the
      secondary and back-scatter modes of the scanning electron microscope. The bond
      strength of all tested adhesives decreased significantly after 100 or more days
      in water. The interfacial observations showed an oxygen-inhibition zone as
      electron lucent in the adhesive-composite border in control specimens, displaying
      silver impregnation with breakage after aging. The deterioration of the oxygen
      inhibition zone in the adhesive-resin composite junction resulted in a decrease
      in bond strength after 100 d in water for one-bottle self-etching adhesives.

PMID- 19758261
TI  - Analysis of differential artificial ageing of the adhesive interface produced by
      a two-step etch-and-rinse adhesive.
AB  - This study was performed to evaluate the effects of different in vitro ageing
      techniques on the dentine-bonded interface produced by a two-step etch-and-rinse
      adhesive. Composite build-ups were bonded to sectioned human molars using XP BOND
      and cut into non-trimmed dentine-composite beams for microtensile testing. Beams
      were assigned to one of the following storage conditions: (i) artificial saliva,
      24 h (control); (ii) 10% sodium hypochlorite (NaOCl), 1 h; (iii) 10% NaOCl, 3 h;
      (iv) 60,000 thermal cycles, 2 months; (v) artificial saliva, 2 months; (vi)
      60,000 thermal cycles, 6 months; and (vii) artificial saliva, 6 months. Beams
      were then pulled until failure and bond strength was calculated. Additional
      specimens were examined to investigate interfacial nanoleakage expression. NaOCl
      solution significantly reduced bonding compared with the control (group 2 = group
      3 < group 1); and thermocycling reduced the bond strength in comparison to
      specimens stored for the same time-period in artificial saliva (group 4 < group
      5; group 6 < group 7). Artificial ageing affected bond strength only after 6
      months of storage (group 7 < group 5 = group 1). Increased nanoleakage was found
      under all ageing conditions in comparison with controls. NaOCl solution is a
      rapid and reliable in vitro ageing method for examining the durability of the
      adhesive interface produced by two-step etch-and-rinse adhesive systems.

PMID- 19758262
TI  - Ageing appearance in China: biophysical profile of facial skin and its
      relationship to perceived age.
AB  - BACKGROUND: Perceived age is important to women and is a primary driver for
      topical product use and facial cosmetic surgery. Changes in facial features and
      biophysical skin parameters with chronological age and their associations with
      perceived age have not been described in Asian populations. OBJECTIVE: To
      investigate the relationship between biophysical properties of the skin, visual
      features of skin ageing and perceived facial age in Chinese women. METHODS:
      Facial photographs were collected of 250 Chinese women, aged 25-70 years in
      Shanghai, China. The perceived facial age was determined and related to the
      chronological age for each participant and to a range of visual assessments of
      skin appearance and objective biophysical measurements of the skin. The profile
      of changes in these parameters with age was investigated together with the
      differences in those parameters for women judged to look younger than their
      chronological age and those judged to look older than their chronological age.
      RESULTS: Large discrepancies in perceived age (up to 29 years) were found in
      women of the same chronological age. Each objective skin measure and visual
      assessment parameter had a stronger correlation with perceived age than with
      chronological age. The strongest relationships to perceived age were for wrinkles
      and hyperpigmentation. Skin colour, hydration and trans-epidermal water loss
      (TEWL) had weaker associations with perceived age. Women judged to look older
      than their chronological age had significantly higher scores than those judged to
      look younger for coarse wrinkles and hyperpigmentation across all age groups. The
      appearance differences between these groups were evident in composite facial
      images of the same average chronological age. CONCLUSIONS: We have identified the
      skin attributes which differ with perceived age in Chinese women. Perceived age
      is a better measure of the biological age of facial skin than is chronological
      age in this population.

PMID- 19758263
TI  - A familial case of tricho-rhino-phalangeal syndrome type III with a novel
      missense mutation in exon 6 of the TRPS1 gene.

PMID- 19758264
TI  - The spectrum of mucocutaneous manifestations in Adamantiades-Behcet's disease in
      Greece.
AB  - BACKGROUND: This is the largest specific demographic and clinical study performed
      until now in Greece. OBJECTIVES: To analyse the spectrum of mucocutaneous
      manifestations in 202 patients with Adamantiades-Behcet's disease (ABD) in
      Greece. METHODS: Any mucocutaneous symptom at disease onset and during the follow
      up was recorded in a particular questionnaire that included 58 items. All
      patients fulfilled the International Study Group Criteria for BD. RESULTS:
      Consecutive patients (130 men and 72 women) were included in this study. Their
      mean age was 42.03 +/- 12.41 and 44.96 +/- 11.99 years for male and female
      patients respectively. Pathergy test was positive in 38%, whereas HLA-B5 (51)
      positivity was evident in 76% of patients. Onset signs: oral aphthous ulcers were
      found in 64.36%, genital ulcers in 6.93%, skin lesions in 8.91%, erythema nodosum
      in 7.42% and pseudofolliculitis in 1.5%. One patient had leg ulcers. During the
      follow-up, oral aphthous ulcers were found in 100%, genital ulcers in 65.4% and
      in 51.4%, erythema nodosum in 42.9% and in 78.1%, whereas pseudofolliculitis in
      57.1% and in 21.9% in men and women respectively. Significant differences
      pointing to a different course of mucocutaneous disease were found between men
      and women. CONCLUSIONS: The nature and frequency of mucocutaneous manifestations
      at presentation are important for the diagnosis of ABD, whereas significant
      differences were found between genders in this Greek patient cohort. Significant
      differences were also observed when our results were compared with those of four
      other series, probably explained by genetic and environmental factors.

PMID- 19758265
TI  - Horizontal stretching concept in oncologic dermatologic surgery of the face.
AB  - BACKGROUND: Skin cancer surgery is usually performed on the face, and more
      specifically on and around the midfacial apertures. Each defect generated by the
      exeresis of a face tumor can be repaired by various advancement, rotation or
      transposition flaps techniques. Therefore the choice of the closure axis of a
      defect and its cicatricial and orificial consequences is decisive. RESULTS: The
      closure of a defect is usually made by symmetrically suturing its edges, across
      the incision axis according to the rule of halves. However, the closure axis of a
      defect is intentional and characterized by the subcutaneous suture axis which
      determines the induced tension orientation, and thus the possible displacement of
      the aperture free margins. The horizontal stretching principle guarantees the
      lack of impact on the 3 major apertures of the midfacial frame: eye, nostril and
      mouth. CONCLUSIONS: This biomechanical concept is decisive to repair midfacial
      defect with functional and aesthetic results. It also provides objective
      arguments for the reparative techniques prioritization and the ability to codify
      those to be recommended as first-line treatment in the surgical management of the
      face cutaneous tumours.

PMID- 19758266
TI  - Patient HSP70-hom TG haplotype is associated with decreased transplant-related
      mortality and improved survival after sibling HLA-matched hematopoietic stem cell
      transplantation.
AB  - Heat shock protein 70-hom (HSP70-hom) plays an important role in protein folding
      and immune responses. Therefore, HSP70-hom gene polymorphisms may act as
      important factors in predicting the prognosis of patients receiving allogeneic
      hematopoietic stem cell transplantation (HSCT). To evaluate the role of HSP70-hom
      gene polymorphisms in the prognosis of patients receiving sibling human leukocyte
      antigen (HLA)-matched allogeneic HSCT, the HSP70-hom polymorphisms, T2437C and
      G2763A, were genotyped in 147 patients receiving sibling HLA-matched allogeneic
      HSCT. Individual diplotypes were estimated from genotype data of the two HSP70
      hom polymorphisms using the expectation maximization algorithm. Patients with the
      2763GG or GA genotype showed longer overall survival compared with those with the
      2763AA genotype, and patients with a TG haplotype (TG/TA, TG/TG or TG/CG) also
      showed longer overall survival compared with those with a non-TG haplotype (TA/TA
      or TA/CG) (both G2763A genotype and diplotype, p<0.01). Moreover, the 2437TT
      genotype was found to be protective for treatment-related death compared with the
      2437TC genotype, and a TG haplotype was found to be very protective for treatment
      related death compared with a non-TG haplotype (T2437C genotype, p=0.04; and
      diplotype, p=0.02). Therefore, our results suggest that HSP70-hom polymorphisms
      play an important role in the prognosis of patients receiving sibling HLA-matched
      allogeneic HSCT.

PMID- 19758267
TI  - Acute rejection in low-toxicity regimens: clinical impact and risk factors in the
      Symphony study.
AB  - The Symphony study assessed whether mycophenolate mofetil (MMF)-based regimens
      containing reduced doses of adjunct immunosuppressants could reduce toxicity
      while maintaining efficacy. Here, we examined the impact of acute rejection and
      associated risk factors. The incidence of biopsy-proven acute rejection in the
      low-dose tacrolimus group was approximately half that of the standard-dose
      cyclosporine and low-dose cyclosporine groups, and a third of that in the low
      dose sirolimus group. The low-dose cyclosporine group had more severe rejection
      episodes (>=grade II) compared with other groups. Acute rejection was associated
      with a 10 mL/min glomerular filtration rate (GFR) reduction and a 5.3% absolute
      increase in graft loss at 12 months. Overall, the highest GFR was found in both
      rejecters and non-rejecters receiving low-dose tacrolimus, both in an intent-to
      treat analysis and in patients successfully treated according to the protocol. In
      Cox regression models, human leukocyte antigen (HLA) mismatches and expanded
      criteria donors increased the acute rejection risk, while recipient age, living
      related donor, and MMF dose were associated with a reduced risk. Acute rejection
      was associated with worse outcome but did not entirely explain the differences
      among the treatment groups. The 2 g MMF plus low-dose tacrolimus combination
      appears to be the most efficient of all regimens examined regardless of acute
      rejection.

PMID- 19758268
TI  - Non-organ-specific and anti-endothelial antibodies in relation to CMV infection
      and acute rejection in renal transplant recipients.
AB  - The presence of non-organ-specific (NOSA) and anti-endothelial antibodies (AECAs)
      and the onset of rejection in relation to cytomegalovirus (CMV) infection was
      investigated in 96 renal transplant recipients: 48 CMV pp65-antigenemia-negative
      (group 1) and 48 positive (group 2). The presence of autoantibodies (autoAbs) was
      evaluated before and following renal transplantation (first three months) by
      indirect immunofluorescence. Before transplantation, none of the patients was
      positive to AECAs, while eight (8.3%) were positive to NOSAs. Post
      transplantation, AECA were found in none of patients from group 1 vs. 15/48
      (31.2%) from group 2 (p<0.05); NOSAs were detected in 9/48 (18.8%) and 9/48
      patients from group 1 and 2, respectively. An acute rejection was diagnosed in
      ten cases: six of interstitial type (antigenemia-, and AECA-negative; two NOSA
      positive); four of vascular type (all of them NOSA-negative, 3/4 antigenemia-,
      and AECA-positive). CMV infection did not seem to be significantly associated
      with the appearance of NOSAs, while there was a significant correlation with the
      occurrence of AECAs. No significant correlation was found between acute rejection
      and the occurrence of NOSAs, while 75% of the cases of vascular rejection was
      associated to CMV infection and AECA-positivity, suggesting the pathogenic role
      of CMV-mediated endothelial damage.

PMID- 19758269
TI  - Response to adefovir or entecavir in renal allograft recipients with hepatitic
      flare due to lamivudine-resistant hepatitis B.
AB  - We studied the effects of adefovir or entecavir in six kidney transplant
      recipients (mean age 45.7 +/- 7.8 yr) who developed hepatitic flare due to
      lamivudine-resistant hepatitis B virus (HBV) infection, with 18 months of follow
      up. All patients had elevated alanine aminotransferase (ALT) levels and HBV DNA
      >10(5) copies/mL (median 2.15 x 10(8) copies/mL) at baseline. Serum creatinine
      and creatinine clearance levels were 137.8 +/- 59.7 mumol/L and 62.6 +/- 18.7
      mL/min, respectively. Four patients were treated with adefovir and two with
      entecavir. Median HBV DNA decreased to 1.99 x 10(5) copies/mL (p = 0.028) after
      six months, 1.5 x 10(4) copies/mL (p = 0.043) after 12 months, and 7.35 x 10(4)
      copies/mL (p = 0.068) after 18 months of treatment. There was a corresponding
      improvement in ALT (34.5 +/- 19.1 U/L after 18 months, p = 0.029 compared with
      baseline). The rate of HBV DNA suppression was variable, and three patients took
      over six months for the viral load to decrease to <10(5) copies/mL. After 18
      months, HBV DNA was <10(5) copies/mL in four patients and <10(2) copies/mL in one
      patient. Treatment was well-tolerated and renal function remained stable. We
      conclude that both adefovir and entecavir are effective in the treatment of
      lamivudine-resistant HBV in renal allograft recipients, and the reduction of HBV
      DNA to <10(5) copies/mL could be slow.

PMID- 19758270
TI  - Physical examination of the potential tissue donor, what do European tissue banks
      do?
AB  - According to the EU Directive 2006/17/EC, European tissue banks are required to
      perform a physical examination on every potential tissue donor. The directive
      itself, however, does not specify the content of this examination. The aim of
      this study was to investigate the current practice of physical examination in
      European tissue banks. A questionnaire was drawn up and sent to the members of
      the European Association of Tissue Banks and the European Eye Bank Association.
      Information was gathered on the type of procurement; the personnel involved
      (number, educational background and training); the content of physical
      examination; the problems encountered; and the outcome of the performed physical
      examinations. Completed questionnaires were received from 32 European tissue
      banks (response rate of 35%). Of these tissue banks, 73% perform a physical
      examination. The most frequently encountered problems are the inability to open
      the mouth due to rigor mortis, the inability to examine the total body surface
      and the incapacity to palpate the lymph nodes. Tissue banks reject potential
      donors, based on the results of the physical examination in 5% of cases (median
      rejection rate). Twenty-seven percent of the responding tissue banks do not
      perform a physical examination. This was most often due to a lack of adequate
      educational background and/or a lack of appropriate training.

PMID- 19758271
TI  - GB virus type C interactions with HIV: the role of envelope glycoproteins.
AB  - GB virus C/hepatitis G virus (GBV-C/HGV) is the most closely related human virus
      to hepatitis C virus (HCV). GBV-C is lymphotropic and not associated with any
      known disease, although it is associated with improved survival in HIV-infected
      individuals. In peripheral blood mononuclear cells, GBV-C induces the release of
      soluble ligands for HIV entry receptors (RANTES, MIP-1a, MIP-1b and SDF-1),
      suggesting that GBV-C may interact with lymphocytes to induce a chemokine and/or
      cytokine milieu that is inhibitory to HIV infection. Expression of GBV-C envelope
      glycoprotein E2 in CD4+ T cells or addition of recombinant E2 to CD4 cells
      recapitulates the HIV inhibition seen with GBV-C infection. Like HCV E2, GBV-C E2
      is predicted to be post-translationally processed in the endoplasmic reticulum
      and is involved with cell binding. The C-termini of GBV-C E1 and E2 proteins
      contain predicted transmembrane domains sharing features with HCV TM domains. To
      date, cellular receptor(s) for GBV-C E2 have not been identified. GBV-C E2
      mediated HIV inhibition is dose-dependent and HIV replication is blocked at the
      binding and/or entry step. In addition, a putative GBV-C E2 fusion peptide
      interferes with HIV gp41 peptide oligomerization required for HIV-1 fusion,
      further suggesting that GBV-C E2 may inhibit HIV entry. Additional work is needed
      to identify the GBV-C E2 cellular receptor, characterize GBV-C E2 domains
      responsible for HIV inhibition, and to examine GBV-C E2-mediated fusion in the
      context of the entire envelope protein or viral-particles. Understanding the
      mechanisms of action may identify novel approaches to HIV therapy.

PMID- 19758272
TI  - Safety and efficacy of an escalating dose regimen of pegylated interferon alpha
      2b in the treatment of haemodialysis patients with chronic hepatitis C.
AB  - Chronic hepatitis C is associated with increased morbidity and mortality in
      persons undergoing haemodialysis. This single-arm, open-label clinical trial
      investigated the safety and efficacy of an escalating dosage regimen of pegylated
      interferon (PEG-IFN) alpha-2b in this patient population. Patients with chronic
      hepatitis C who were undergoing haemodialysis began treatment with PEG-IFN alpha
      2b at a dose of 0.5 microg/kg/week, which was increased every 4 weeks to a
      maximum of 1 microg/kg/week. Treatment duration was 24 weeks for patients with
      genotype (G) 2 or 3 infection and 48 weeks for patients with G1 infection. The
      primary end point was sustained virological response (SVR). Of 46 patients
      screened, 34 (G1: 70.6%; G3: 29.4%) were treated and 23 (67.6%) completed
      treatment. Overall, 85.3% of patients experienced early virological response,
      52.9% experienced end-of-treatment response, and 50% attained SVR, with a trend
      toward higher SVR rates in G3 compared with G1 patients (80%vs 37.5%; P = 0.06).
      Anaemia was the main reason for discontinuation of treatment. Patients with
      chronic hepatitis C who are undergoing haemodialysis can be successfully treated
      with an escalating dosage regimen of PEG-IFN alpha-2b monotherapy. G3-infected
      patients can attain high rates of SVR with only 24 weeks of therapy.

PMID- 19758273
TI  - Prediction of significant liver fibrosis in kidney transplant patients with
      chronic hepatitis C virus infection: the TX-3 index.
AB  - HCV infection is highly prevalent among kidney transplant (KT) recipients. The
      natural history and management of these patients are controversial. We sought to
      assess the diagnostic value of noninvasive markers of liver fibrosis in KT HCV
      infected patients. This cross-sectional study included 102 KT individuals with
      positive HCV-RNA. Bivariate and multivariate analyses were used to identify
      variables associated with significant fibrosis (METAVIR > or = F2). Significant
      fibrosis was observed in 20 patients (20%). Time after transplantation, AST
      level, and platelet count were identified as independent predictors of
      significant fibrosis. Based on the regression model, a simplified index was
      devised. The AUROC for the TX-3 model was 0.867 +/- 0.081 (0.909, when adjusted
      by DANA). Values < or =4.0 of TX-3 showed a NPV of 97% and scores >9.6 exhibited
      a PPV of 71%. If biopsy indication was restricted to scores in the intermediate
      range of TX-3, this could have been correctly avoided in 68% of cases. The APRI
      score provided a correct diagnosis in only 47 individuals (46%) and exhibited
      lower diagnostic indices for both cutoffs, as compared to the TX-3 index.
      Comparison of AUROCs showed a trend towards superior diagnostic accuracy for TX-3
      over APRI, although the difference between AUROCs did not reach statistical
      significance (0.867 +/- 0.053 vs 0.762 +/- 0.066, respectively, P = 0.064). In
      conclusion, significant liver fibrosis can be reliably predicted in KT HCV
      infected subjects by simple and widely available parameters. If additional
      studies confirm our results, this model might obviate the requirement for a liver
      biopsy in a significant proportion of those patients.

PMID- 19758274
TI  - Hepatitis C Virus-related chronic liver disease in elderly patients: an Italian
      cross-sectional study.
AB  - Chronic hepatitis C virus (HCV) infection has been poorly investigated in the
      elderly. The aim of this study was to identify the age-specific characteristics
      of chronic hepatitis C by comparing patients > or =65 years with those <65 years.
      A cross-sectional study was performed on data collected from consecutive
      outpatients referred for the first time to two tertiary outpatient clinics for
      liver diseases located in Bologna (Northern Italy) and Paola, Cosenza (Southern
      Italy) over a two-year period. A total of 560 anti-HCV and HCV-RNA positive
      patients were enrolled, of whom 174 (31%) were 65 years or older. The proportion
      of older patients was significantly higher in the Southern Italy centre,
      accounting for more than 40%. Comparison of younger and older groups showed that
      51% patients > or =65 years had advanced liver disease (liver cirrhosis or
      hepatocellular carcinoma) compared with 26% younger patients (P < 0.0001). About
      half of the patients > or =65 years were not aware of their anti-HCV positive
      status, even if they tended to be more symptomatic than the younger group. By
      multivariate analysis, age > or = 65 years, alcohol consumption and diabetes were
      independently associated with advanced liver disease. Overall, 34 out of 174
      patients (20%) > or =65 years had received antiviral treatment compared with 122
      out of 386 (32%) younger patients (P = 0.003). Our results further emphasize the
      notion that chronic hepatitis C is becoming a disease of the elderly and that
      elderly patients with chronic HCV infection often have severe and underestimated
      disease.

PMID- 19758275
TI  - Investigating health-related quality of life, mood and neuropsychological test
      performance in a homogeneous cohort of Irish female hepatitis C patients.
AB  - Neurocognitive dysfunction has been reported in individuals with chronic
      hepatitis C (CHC) infection, but HCV populations investigated have often included
      participants with numerous potential confounding comorbidities. This pilot study
      sought to investigate functional capacity and neurocognitive function in a
      homogeneous state-infected HCV population with histologically defined mild liver
      disease, free from the comorbid factors typically associated with HCV
      populations. A further aim was to examine cognitive function in a treatment naive
      population with a similar history of iatrogenic HCV exposure and spontaneous
      viral clearance. A convenience sample of 29 women, all of whom were carefully
      screened to exclude relevant comorbidities, was recruited to the study. Twenty
      women with a history of iatrogenic HCV exposure were recruited from prospective
      specialist tertiary care liver clinics. A comparison group of healthy controls (n
      = 9) was also assessed. Study participants underwent mood, health-related quality
      of life and neuropsychological assessment. CHC patients reported significantly
      higher levels of cognitive fatigue than healthy controls (F = 3.4, P = 0.04). On
      cognitive testing, CHC patients showed impairments compared with healthy controls
      on estimates of general memory [F(2,25) = 4.1, P = 0.03, partial eta squared =
      0.25], delayed auditory recognition [F(2,25) = 4.2, P = 0.03, partial eta
      squared= 0.22] and sustained attention [F(2,25) = 3.6, P = 0.04, partial eta
      squared = 0.22]. Increased cognitive fatigue only correlated with delayed
      auditory memory recall ability (r = 0.724, P = 0.006). In conclusion, these
      findings appear to support the presence of neurocognitive abnormalities in an
      iatrogenically infected, homogeneous female HCV population who were carefully
      screened to eliminate other factors affecting neurocognitive test performance and
      may indicate underlying neurophysiological causative mechanisms.

PMID- 19758276
TI  - In vivo effects of fluvastatin on HCV replication in HIV-1 coinfected subjects.

PMID- 19758277
TI  - Does fluvastatin favour HCV replication in vivo? A pilot study on HIV-HCV co
      infected patients.

PMID- 19758278
TI  - Stringent cessation criterion results in better durability of lamivudine
      treatment: a prospective clinical study in hepatitis B e antigen-positive chronic
      hepatitis B patients.
AB  - The cessation criteria for lamivudine treatment vary in published articles and
      their results are contradictory, especially factors predicting relapse. To
      clarify these contradictions, this long-term follow-up study of 125 Chinese
      hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients was designed
      with stringent cessation criterion. All patients received lamivudine and achieved
      HBeAg seroconversion (group A, n = 82) or loss (group B, n = 43) with
      undetectable hepatitis B virus (HBV) DNA by PCR assay during the treatment.
      Lamivudine was withdrawn >or=6 months after HBeAg seroconversion/loss occurred.
      The median treatment durations were 24 (12-54) months and 36 (18-89) months in
      group A and group B, respectively. Patients were followed up for median 24 (2-84)
      months. The cumulative relapse (defined as serum HBV DNA >or=10(4) copies/mL)
      rates in the two groups at months 12, 24, 36 and 48 were 23.4%vs 35.0%, 25.0%vs
      37.7%, 25.0%vs 41.1% and 29.4%vs 41.1%, respectively (log-rank test, P = 0.119).
      For patients whose total treatment duration >or=18 months in group A, the
      cumulative relapse rates at months 12, 24, 36 and 48 were 18.3%, 20.1%, 20.1% and
      25.1%, which was significantly lower than those with a shorter duration (log-rank
      test, P = 0.002). The mean age and median total duration were statistically
      different between relapsers and nonrelapsers in group A (33.9 +/- 13.6 vs 23.1 +/
      11.0 years, P < 0.001 and 24 vs 26 months, P = 0.003). Cox regression revealed
      that age was the only predictive factor for relapse (RR, 1.069; 95% CI, 1.032
      1.106, P < 0.001). Patients aged <30 years relapsed less frequently in 5 years
      (12.3%vs 53.5%, P = 0.001). In conclusion, for patients who maintained HBeAg
      seroconversion for >or=6 months and total duration for >or=18 months, lamivudine
      withdrawal is a reasonable option. Prolonged treatment may be required for
      patients aged greater than 30 years to reduce relapse.

PMID- 19758279
TI  - Effect of ribavirin on the frequency of RNase L cleavage sites within the
      hepatitis C viral genome.
AB  - The mechanisms of synergy in antiviral activity of interferon-alpha and ribavirin
      in treating chronic hepatitis C virus (HCV) infection are still unknown.
      Interferon-alpha indirectly induces cleavage of viral RNA by RNase L at UU/UA
      dinucleotides. There is evidence that HCV genomes with a higher number of UU/UA
      dinucleotides are more sensitive to interferon-alpha. As a guanosine analogue,
      ribavirin exerts a mutagenic effect promoting G-to-A and C-to-U transitions. This
      study investigates whether ribavirin-induced mutagenesis causes a higher
      frequency of UU/UA dinucleotides in the viral progeny sequences. Increased
      mutational frequencies in favour of G-to-A and C-to-U transitions during
      ribavirin treatment was reported by Hofmann et al. (Gastroenterology 2007;132:921
      930). Overall, 937 nucleotide sequences from that publication were reanalysed for
      RNase L cleavage sites. These included HCV NS3 quasispecies from three patients
      with ribavirin monotherapy and NS5B quasispecies from patients who received
      ribavirin alone (n = 7) or in combination with interferon-alpha (n = 7) at
      baseline and during treatment; NS5B quasispecies from a subgenomic HCV replicon
      system after 24, 48 and 72 h of cultivation with or without ribavirin or with
      levovirin. For NS3 quasispecies during ribavirin monotherapy and NS5B
      quasispecies from patients who received ribavirin alone or in combination with
      interferon-alpha, analysis of RNase L cleavage sites did not reveal changes
      during treatment or differences between treatment regimes. Similarly, RNaseL
      cleavage sites from NS5B quasispecies of the HCV replicon did not differ
      significantly between time points or treatments. In conclusion, Ribavirin-induced
      mutagenesis did not increase RNase L cleavage sites (UU/UA dinucleotides) within
      the HCV NS3 or NS5B encoding regions.

PMID- 19758280
TI  - The Arabic version of the Erection Hardness Score.

PMID- 19758281
TI  - Design and application of a new rat-specific vacuum erectile device for penile
      rehabilitation research.
AB  - INTRODUCTION: Radical prostatectomy has a potential negative impact on penile
      health. The vacuum erection device (VED) has been used to promote the recovery of
      penile function and to maintain penile length. However, there is skepticism in
      the urological community due to its elusive mechanisms in penile rehabilitation.
      AIM: To design a rat-specific VED and assess its application and safety. METHODS:
      Based on rat penile measurement and the principle of human VED, the rat-specific
      VED was designed, and the application for rats was evaluated. MAIN OUTCOME
      MEASURES: The vacuum pressure of the rat-specific VED was measured. The VED
      application on rat penis and its side effects were studied. RESULTS: The rat
      specific VED is a safe and applicable device to study the mechanism of VED in
      penile rehabilitation. CONCLUSIONS: The newly designed rat-specific VED is a good
      simulator of the human VED. The application of this device on bilateral cavernous
      nerve crush rat model will be used to study the mechanisms of the VED in the
      penile rehabilitation.

PMID- 19758282
TI  - Patient and partner satisfaction after AMS inflatable penile prosthesis implant.
AB  - INTRODUCTION: The implantation of penile prostheses is an effective option for
      treating erectile dysfunction (ED), and nowadays it is used to treat those cases
      where pharmacological agents have not provided a useful result. AIMS: The primary
      aim of the present study was to verify the patient and their partner's
      satisfaction, in 80 patients who underwent AMS CX 700 prostheses implant in a
      single center, by the same surgeon, in the period between 2004 and 2008. METHODS:
      In the period between March 2004 and May 2008, 80 penile prostheses implantations
      have been performed. Any information regarding patients has been retrospectively
      collected consulting their case histories stored in our archive. Each patient was
      followed postoperatively, and surgical complications were recorded. MAIN OUTCOME
      MEASURE: All the patients entered in this study were contacted by phone by a
      single operator who asked for their consent to collect information regarding
      their operation, the use of the prostheses, and the couple satisfaction. Once the
      consent was obtained, a nine-point questionnaire was administered. RESULTS:
      Seventy-six patients (97%) affirmed to use penile prostheses frequently. Fifty
      four patients (69%) and 70 partners (90%) affirmed that they never had problems
      with the use of the prosthesis and they considered themselves satisfied. Sixty
      two patients (79%) answered that this therapeutic method has led to evident
      improvements in their sexual life. Sixty-two patients (79%) gave a score equal or
      major than seven and sixty-four partners (82%) gave a score equal or major than
      seven. All but two patients (97%) reported they would suggest this treatment to
      other people. CONCLUSIONS: Penile prosthetic surgery constitutes a valid
      therapeutic alternative, capable of modifying the prognosis and the course of ED.
      This consideration is emphasized by the high rate of patients and partner's
      satisfaction emerged in our series and in literature.

PMID- 19758283
TI  - Female sexual arousal disorder with and without a distress criterion: prevalence
      and correlates in a representative Czech sample.
AB  - INTRODUCTION: Sexual medicine would benefit from large representative surveys
      examining the prevalence of genital female sexual arousal disorder (FSAD)
      symptoms (with and without the increasingly controversial distress criterion), as
      well as novel FSAD correlates and potential "protective" factors. AIMS: To
      examine the extent to which genital FSAD symptoms, with and without a distress
      criterion, are associated with both historical and current aspects of sexual
      behavior. METHODS: In a representative sample of the Czech population (aged 15
      88), 1,000 women were asked whether they currently have impaired lubrication and
      vaginal swelling (and if so, if this produces marked distress or interpersonal
      difficulty). They provided details of vaginal orgasm (induced by penile-vaginal
      intercourse [PVI] without clitoral masturbation) consistency, feelings during
      their first PVI, estimates of their typical foreplay and PVI durations, their
      degree of mental focus on vaginal sensations during PVI, among other factors.
      MAIN OUTCOME MEASURES: The current prevalence of FSAD with and without a distress
      criterion and their associations with current and antecedent sexual behaviors and
      responses. RESULTS: The current prevalence of FSAD was 10.3% without, plus 7.5%
      with a distress criterion (which tended to be associated with more impairments
      than without distress). History of vaginal orgasm (odds ratio = 2.78), never
      masturbating (odds ratio = 2.4), not having felt pain and discomfort on first PVI
      (odds ratio = 2.27), and not having frequent anal intercourse are protective
      against FSAD with distress, but not without distress. Age (especially over 50)
      and inadequate focusing of mental attention on vaginal sensations during PVI are
      associated with increased FSAD risk both with and without distress. CONCLUSIONS:
      FSAD with and without distress appear to be different entities to some extent,
      with the distressed group showing more long-term signs of psychosexual
      impairment. We suggest that FSAD with and without distress be considered two
      different disorders.

PMID- 19758284
TI  - Autoeroticism, mental health, and organic disturbances in patients with erectile
      dysfunction.
AB  - INTRODUCTION: Masturbation is a common, but often neglected, male sexual
      behavior. AIM: To investigate the psychobiological correlates of self-reported
      masturbation in the last 3 months. METHODS: A consecutive series of 2,786
      heterosexual male patients (mean age 48.4 +/- 13.2) consulting an outpatient
      clinic for erectile dysfunction (ED) was studied. MAIN OUTCOME MEASURES: Several
      hormonal, biochemical and instrumental parameters (penile Doppler ultrasound
      [PDU]) were investigated. Patients were interviewed, prior to the beginning of
      any treatment, with Structured Interview on Erectile Dysfunction (SIEDY) and
      ANDROTEST structured interviews. They also completed the Middlesex Hospital
      Questionnaire, a brief self-reported questionnaire for the screening of the
      symptoms of mental disorders in a nonpsychiatric setting. RESULTS: Among the
      patients studied, 1,781 (61.9%) reported they had masturbated at least once per
      month in the preceding 3 months. The frequency of masturbation was inversely
      related to age (r = -0.329; P < 0.0001) and directly associated with education
      level (adj r = 0.052, P < 0.05 after adjustment for age). A feeling of guilt
      during masturbation was reported by 274 (15.4%) patients. After adjusting for
      age, masturbation was positively associated with testosterone levels, stressful
      conditions, and both unstable and long-lasting couple relationship. Urogenital
      problems such as varicocele and prostate abnormalities also increased the chance
      of masturbation. Reported guiltiness during autoeroticism was associated with
      psychological disturbances, low prolactin, low testosterone, and increased
      relational problems. An erection not normal during masturbation was declared by
      1,361 (76.4%) patients and associated with a prevalent organic component of ED,
      because of lower peak systolic velocity PDU and higher SIEDY Scale 1 scores.
      CONCLUSIONS: This study indicates that masturbation is a relatively frequent
      behavior in male subjects with ED. Inquiring about this sexual behavior is an
      important issue for understanding overall patients' sexual attitudes and
      behavior.

PMID- 19758285
TI  - The management of erectile dysfunction with placebo only: does it work?
AB  - INTRODUCTION: Randomized clinical trials (RCT) remain the gold standard in
      providing scientific evidence in medical practice in spite of the significant
      placebo effect in the treatment of several disorders. Although the first-line
      therapy for erectile dysfunction (ED) is oral phosphodiesterase type-5 inhibitor
      (iPDE5), the placebo effect in RCT of iPDE5 for ED occurs at a rate as high as
      50%. AIMS: To evaluate the role of therapeutic illusion in the oral treatment for
      ED. METHODS: A prospective, controlled, single-blind, parallel-group study was
      performed at single-center. One hundred and twenty-three patients with ED were
      randomly assigned into three groups and received different letters: Group 1 (G1)
      was informed to be receiving a substance for ED treatment; Group 2 (G2) was
      informed that they could be receiving an active drug or placebo; Group 3 (G3) was
      conscious to be using placebo. Starch capsules were dispensed to all patients.
      Median follow up was 12 weeks. MAIN OUTCOME MEASURES: ED improvement was assessed
      after 8 weeks of the intervention by the erectile function domain of the
      International Index of Erectile Function (IIEF) and the Quality of Erection
      Questionnaire. ED severity was classified by the IIEF erectile function (IIEF-EF)
      domain score into five categories: no ED (score of 26-30), mild (22-25), mild to
      moderate (17-21), moderate (11-16), and severe (6-10). Improvement in IIEF-EF
      domain was considered as a change in category of severity. RESULTS: ED severity
      improved in all three groups (G1 = 31.7%, P = 0.039; G2 = 36.8%, P = 0.028; G3 =
      36.8%, P = 0.002) and no difference was found among groups (P = 0.857).
      Improvement of quality of erection score was only significant in G2 (P = 0.005)
      and G3 (P < 0.001). CONCLUSIONS: Written-suggested therapeutic illusion for
      patients with ED has no major influence in the outcomes. However, treatment of ED
      with oral placebo capsules demonstrates clinical effects, improving erectile
      function and quality of erection.

PMID- 19758286
TI  - Female youth who sexually coerce: prevalence, risk, and protective factors in two
      national high school surveys.
AB  - INTRODUCTION: Sexual coercion is recognized as a serious societal problem.
      Correlates and risk factors of sexually abusive behavior in females are not well
      known. AIM: Etiological theory and empirical study of female perpetrators of
      sexual coercion are usually based on small or highly selected samples.
      Specifically, population-based data are needed to elucidate risk/protective
      factors. MAIN OUTCOME MEASURES: Main outcome measures include a self-report
      questionnaire containing 65 items tapping socio-demographic and health
      conditions, social relations, sexual victimization, conduct problems and a set of
      normative and deviant sexual cognitions, attitudes, and behaviors. METHODS: We
      used a 2003-2004 survey of sexual attitudes and experiences among high school
      students in Norway and Sweden to identify risk factors and correlates to sexually
      coercive behavior (response rate 80%); 4,363 females participated (Mean = 18.1
      years). RESULTS: Thirty-seven women (0.8%) reported sexual coercion (ever talked
      someone into, used pressure, or forced somebody to have sex). Sexually coercive
      compared with non-coercive women were similar on socio-demographic variables, but
      reported less parental care and more parental overprotection, aggression,
      depressive symptoms, and substance misuse. Also, sexually coercive females
      reported more sexual lust, sex partners, penetrative sexual victimization, rape
      myths, use of violent porn, and friends more likely to use porn. When using the
      Swedish subsample to differentiate risk factors specific for sexual coercion from
      those for antisocial behavior in general, we found less cannabis use, but more
      sexual preoccupation, pro-rape attitudes, and friends using violent porn in
      sexually coercive compared with non-sex conduct problem females. CONCLUSIONS:
      Sexually coercive behavior in high school women was associated with general
      risk/needs factors for antisocial behavior, but also with specific sexuality
      related risk factors. This differential effect has previously been overlooked,
      agrees with similar findings in men, and should have substantial etiological
      importance.

PMID- 19758287
TI  - Risk factors for individual domains of female sexual function.
AB  - INTRODUCTION: Female sexual function contains four major subtypes of desire,
      arousal, orgasm, and pain. Few studies used validated instruments to determine
      the dysfunction in these areas and assess their risk factors. AIM: To assess the
      prevalence of and risk factors for individual components of sexual difficulty in
      women. METHODS: A self-administered questionnaire containing the Female Sexual
      Function Index (FSFI) was given to 2,159 woman employees of two hospitals to
      assess their sexual function and its correlates. MAIN OUTCOME MEASURES: The
      associations between female sexual difficulty in individual domains defined by
      the FSFI domain scores and potential risk factors assessed by simple questions.
      RESULTS: Among the 1,580 respondents, 930 women's data were eligible for analysis
      with a mean age of 36.1 years (range 20-67). Of them, 43.8% had sexual difficulty
      in one or more domains, including low desire in 31.3%; low arousal, 18.2%; low
      lubrication, 4.8%; low orgasmic function, 10.4%; low satisfaction, 7.3%; and
      sexual pain, 10.5%. Compared with the younger women (20-49 years), the oldest age
      group (50-67 years) had a significantly higher prevalence in low desire, low
      arousal, and low lubrication, but not in the other domains. Based on multivariate
      logistic regression analyses, poor relationship with the partner and perception
      of partner's sexual dysfunction were major risk factors for low desire, low
      arousal, low orgasmic function, and low satisfaction. Age and urge urinary
      incontinence were associated with low lubrication and sexual pain. Most
      comorbidities were not related to these difficulties, except diabetes being
      related to low desire. CONCLUSIONS: Relationship factors had substantial impact
      on female sexual function in desire, arousal, orgasm, and satisfaction. On the
      other hand, women's lubrication problem and sexual pain were related
      predominantly with biological factors. These are initial results and future
      research is needed to confirm them.

PMID- 19758288
TI  - Reliability of maximum bite force measurements in age-varying populations.
AB  - In order for bite forces to be used clinically, they must be reliable. While bite
      force transducers are accurate and precise during bench tests, widely varying
      reliabilities of intra-oral bite forces have been reported when measured in human
      subjects. Because few studies have reported total reliability, the clinical use
      of intra-oral bite forces measurements remains questionable. The purposes of this
      study were to (i) estimate total reliability, including both within- and between
      session reliabilities, of repeated maximum incisor and molar bite force
      measurements and (ii) demonstrate how extraneous variation affects reliability by
      comparing estimates for which the effects of age have and have not been
      controlled. A sample of 28 healthy subjects with Class I normal occlusion (seven
      subjects in each of four age groups: 5, 8, 11 and 14 years) performed two
      sessions approximately 90 min apart. Each session consisted of three maximum
      voluntary bites at three bite positions (incisor and right and left molars). For
      each bite position, between-subject variance (true variance), between-session
      variance and within-session variance were calculated using Multilevel modelling
      procedures. The variances were used to estimate between-session reliabilities,
      within-session reliabilities and total reliabilities. Within-session
      reliabilities were substantially higher than between-session reliabilities, which
      in turn was higher than total reliabilities at all bite positions. Reliabilities
      were highest at the incisor bite position. Not controlling for age effects
      substantially overestimated total reliability at all bite positions. After
      controlling for age effects, total reliabilities of repeated maximum bite forces
      were low to moderate.

PMID- 19758289
TI  - Thromboembolism and rebleeding paradox in stent-assisted embolization for
      intracranial aneurysms.

PMID- 19758290
TI  - Investigating agenesis of the corpus callosum using functional MRI: a study
      examining interhemispheric coordination of motor control.
AB  - We report fMRI findings in 3 asymptomatic cases of agenesis of the corpus
      callosum, the largest white matter bundle in the brain, which is responsible for
      interhemispheric transfer of information. Sensory information was presented to 1
      hemisphere, and the patients had to generate a motor response governed by the
      contralateral hemisphere. Enhanced ipsilateral motor pathways have been suggested
      as a compensation method for people with agenesis of the corpus callosums; our
      functional magnetic resonance imaging data did not support this theory.

PMID- 19758291
TI  - Endovascular treatment of atypical posterior circulation aneurysms: technical
      results and review of the literature.
AB  - BACKGROUND: we report our technical success and complication rates in treating
      posterior circulation aneurysms at sites other than the basilar apex, superior
      cerebellar artery origin, or the posterior inferior cerebellar artery origin via
      endovascular embolization or sacrifice. MATERIALS AND METHODS: we retrospectively
      reviewed case records for patients undergoing coil embolization of atypical
      posterior circulation aneurysms from January 2003 to December 2007. RESULTS:
      thirty-two aneurysms in 32 patients were treated. Twenty-one patients (65%)
      presented with a subarachnoid hemorrhage. Twenty-two aneurysms were treated with
      coiling alone, 9 with stent-assisted coiling, and 1 with a combination of Onyx
      plus stent-assisted coiling. Twelve aneurysms were treated with vessel sacrifice.
      Immediately post procedure, 27/32 aneurysms (84%) were considered successfully
      treated, resulting in either vessel sacrifice, complete obliteration, or minimal
      neck remnant. Sixteen of 19 patients (84%) were considered successfully treated
      at a mean angiographic follow up of 8 months. The procedural morbidity and
      mortality was 15% and 6% respectively. CONCLUSION: endovascular embolization
      remains a viable and durable method of treatment for atypical posterior
      circulation aneurysms.

PMID- 19758292
TI  - Slow conduction or block of the cavotricuspid isthmus-treat or trick?

PMID- 19758293
TI  - The significance of early atrial tachyarrhythmias after catheter ablation of
      atrial fibrillation: a matter of time.

PMID- 19758294
TI  - Acquired perforating dermatoses in patients with diabetic kidney disease on
      hemodialysis.
AB  - Acquired perforating dermatoses (APD) is an uncommon skin disorder seen in
      patients with diabetes mellitus, chronic kidney disease, or both together. We
      present the clinicopathological features of APD in patients with diabetic kidney
      disease and discuss the recent advances in management. We retrospectively
      analyzed the data of 8 patients with APD presenting to our center. All patients
      were known cases of Type 2 diabetes and chronic kidney disease requiring
      maintenance dialysis. Acquired perforating dermatoses was diagnosed based on
      clinical presentation of itchy, keratotic papulonodular lesions, and
      characteristic histopathological features of transepithelial elimination on skin
      biopsy. The patients were subdivided into 4 types of APD based on the biopsy
      features. All our patients had Type 2 diabetes over 5 years duration and were on
      maintenance dialysis for more than 6 months before presentation. Acquired
      perforating dermatoses symptoms appeared 2 to 6 months before presentation. The
      majority of patients (6/8) had a subtype of reactive perforating collagenosis.
      All the patients showed significant resolution with topical glucocorticoid
      therapy. Acquired perforating dermatoses is a skin complication seen in Type 2
      diabetes, chronic kidney disease, or when both are present together. Early
      identification and therapy prevents the associated morbidity.

PMID- 19758295
TI  - Sexual function in women receiving maintenance dialysis.
AB  - While substantial attention has been paid to the issue of sexual dysfunction in
      men on chronic dialysis, less is known about this problem in women with end-stage
      renal disease. We sought to assess sexual dysfunction in women on chronic
      dialysis and determine whether patients discuss this problem with their providers
      and receive treatment. We prospectively enrolled women receiving chronic
      hemodialysis or peritoneal dialysis in Pittsburgh, PA. We asked patients to
      complete the 19-item Female Sexual Function Index (FSFI) to assess sexual
      function and a 5-item survey that assessed whether patients had discussed sexual
      dysfunction with their providers and/or received treatment for this problem in
      the past. We enrolled 66 patients; 59 (89%) on hemodialysis and 7 (11%) on
      peritoneal dialysis. All patients completed the FSFI, of whom 53 (80%) had FSFI
      scores <26.55, consistent with the presence of sexual dysfunction. Of 37 patients
      who were married or residing with a significant other, 27 (73%) had sexual
      dysfunction. Among 24 participants who reported having been sexually active over
      the previous 4 weeks, 11 (46%) had sexual dysfunction. Only 21% of patients with
      sexual dysfunction had discussed this problem with their gynecologist, renal or
      primary provider, and 3 (6%) reported having received treatment. Sexual
      dysfunction is common in women on dialysis, even among patients who are married
      or residing with a significant other and those who are sexually active. However,
      few women discuss this issue with their providers or receive treatment.

PMID- 19758296
TI  - Solute kinetics with short-daily home hemodialysis using slow dialysate flow
      rate.
AB  - "NxStage System One()" is increasingly used for daily home hemodialysis. The
      ultrapure dialysate volumes are typically between 15 L and 30 L per dialysis,
      substantially smaller than the volumes used in conventional dialysis. In this
      study, the impact of the use of low dialysate volumes on the removal rates of
      solutes of different molecular weights and volumes of distribution was evaluated.
      Serum measurements before and after dialysis and total dialysate collection were
      performed over 30 times in 5 functionally anephric patients undergoing short
      daily home hemodialysis (6 d/wk) over the course of 8 to 16 months. Measured
      solutes included beta(2) microglobulin (beta(2)M), phosphorus, urea nitrogen, and
      potassium. The average spent dialysate volume (dialysate plus ultrafiltrate) was
      25.4+/-4.7 L and the dialysis duration was 175+/-15 min. beta(2) microglobulin
      clearance of the polyethersulfone dialyzer averaged 53+/-14 mL/min. Total
      beta(2)M recovered in the dialysate was 106+/-42 mg per treatment (n=38).
      Predialysis serum beta(2)M levels remained stable over the observation period.
      Phosphorus removal averaged 694+/-343 mg per treatment with a mean predialysis
      serum phosphorus of 5.2+/-1.8 mg/dL (n=34). Standard Kt/V averaged 2.5+/-0.3 per
      week and correlated with the dialysate-based weekly Kt/V. Weekly beta(2)M,
      phosphorus, and urea nitrogen removal in patients dialyzing 6 d/wk with these
      relatively low dialysate volumes compared favorably with values published for
      thrice weekly conventional and with short-daily hemodialysis performed with
      machines using much higher dialysate flow rates. Results of the present study
      were achieved, however, with an average of 17.5 hours of dialysis per week.

PMID- 19758297
TI  - Quality of care assessment and adherence to the international guidelines
      considering dialysis, water treatment, and protection against transmission of
      infections in university hospital-based dialysis units in Cairo, Egypt.
AB  - End-stage renal disease has emerged as a major public health problem around the
      world. In recent decades, several important advances have been made in the
      therapy of hemodialysis (HD) with the introduction of international guidelines to
      ensure the delivery of optimum care to HD patients. An increased mortality risk
      in HD patients unable to meet six targets in different areas of HD practice has
      been reported by the Dialysis Outcomes and Practice Patterns Study investigators.
      In this retrospective study, we assessed the current practice patterns of care
      for HD patients in the Kaser El-Aini Nephrology and Dialysis Center in comparison
      with Dialysis Outcomes Quality Initiative Guidelines, European Best Practice
      Guidelines, Centers for Disease Control and Prevention guidelines for prevention
      of transmission of infections among HD patients, and American Association for
      Medical Instrumentation (AAMI) standards for dialysis water quality. The mean
      percent of urea reduction was 63 +/- 8.8% in prevalent HD patients. An
      arteriovenous fistula was the vascular access in 91% of prevalent HD patients,
      whereas a temporary catheter was used in 9% of cases mostly as a bridge till
      arteriovenous fistula creation/maturation. Bicarbonate was the base used in 80%
      of the cases. Ninty-seven percent patients had thrice-weekly sessions and 3% had
      two dialysis sessions/wk. The mean serum albumin was 4.19 +/- 0.39 g/dL; 66.66%
      of prevalent patients had serum albumin level >4 g/dL. The mean serum calcium was
      8.66 +/- 1.4 mg/dL, phosphorus was 6.26 +/- 2.54 mg/dL, and approximately 60% of
      patients had a serum phosphorus level >5.5 mg/dL. The CaxPi product was higher
      than 55 in around 40% of the cases, and the parathyroid hormone level was in the
      range of 150 to 300 pg/mL in around 10% of prevalent patients. The mean
      hemoglobin was 9.23 +/- 7.18 g/dL in prevalent cases; around 70% of cases had a
      hemoglobin level <11 g/dL. Iron deficiency was prevalent as 18% of patients, with
      serum ferritin <200 ng/L, and 34% had total serum test <20%. Seventy percent of
      the patients were hepatitis C virus positive and 4% were hepatitis B surface
      antigen positive, and all were negative for the human immunodeficiency virus
      serological test. Dialysis water was monitored regularly for chemical and
      bacterial contamination as recommended by the American Association for Medical
      Instrumentation, but an endotoxin assay is currently not included in the
      monitoring checklist. The annual mortality rate was 8% in 2007. The current audit
      revealed a reasonable quality of care for HD patients in the fields of vascular
      access care, dialysis adequacy, and nutrition areas. It also reveals the need for
      improving anemia management and control of hyperphosphatemia with dietary
      counseling and more frequent dialysis. To fully meet the guideline targets, each
      patient should be treated in an individualized way with more counseling,
      nutritional education, and individualized dialysis prescription. Besides, the
      unit needs to adopt primary and secondary intervention strategies to prevent and
      promptly correct any deviation from the desired targets.

PMID- 19758298
TI  - Treating mineral metabolism disorders in patients undergoing long hemodialysis: a
      search for an optimal strategy.
AB  - In hemodialysis (HD) patients, mineral metabolism (MM) disorders have been
      associated with an increased mortality rate. We report the evolution of MM
      parameters in a stable HD population undergoing long hemodialysis by performing
      an annual cross-sectional analysis for every year from 1994 to 2008. The
      therapeutic strategy has changed: the dialysate calcium concentration has
      decreased from a mean of 1.7 +/- 0.1 to 1.5 +/- 0.07 mmol/L and has been adapted
      to parathyroid hormone serum levels (from 1 to 1.75 mmol/L). The use of calcium
      based and aluminum-based phosphate binders has decreased and they have been
      replaced by sevelamer; alfacalcidol has partly been replaced by native vitamin D.
      The percentage of patients with a parathyroid hormone serum level between 150 and
      300 pg/mL has increased from 9% to 67% (P<0.001); the percentage of patients with
      phosphataemia between 1.15 and 1.78 mmol/L has increased from 39% to 84%
      (P<0.001). The percentage of those with albumin-corrected calcemia between 2.1
      and 2.37 mmol/L has increased from 29% to 61% (P<0.001), and that of patients
      with a calcium-phosphorous product (Ca x P) level >4.4 mmol/L decreased from 8.8%
      to 2% (P=0.02). Although patients undergo long and intensive HD treatment, MM
      disorders are common. However, an appropriate strategy, mostly consisting of
      native vitamin D supplementation, progressive replacement of calcium-based
      phosphate binders with non-calcium-based ones, and individualization of dialysis
      session duration and dialysate calcium concentration, would result in a drastic
      improvement.

PMID- 19758299
TI  - Variability in calcium, phosphorus, and parathyroid hormone in patients on
      hemodialysis.
AB  - Calcium, phosphorus, and parathyroid hormone (PTH) levels are routinely measured
      in patients undergoing chronic hemodialysis. Medications, diet, and dialytic
      therapies are modified based upon these lab values to achieve specific goal
      values in the hope of improving outcomes. However, the variability of these
      values in patients undergoing chronic hemodialysis has only been rarely studied.
      We prospectively investigated the variability of these measures in 35 patients
      undergoing chronic hemodialysis as well as the impact of this variability on
      clinical decision-making in a prospective manner over a month. There is
      significant session-to-session variability in phosphorus and PTH values (mean
      coefficient of variations [CV] of 0.19 and 0.31, respectively). Calcium
      variability is much lower (mean CV of 0.05). Not surprisingly, the CV for all
      values is increased during the long interdialytic interval. The impact of this
      variability on clinical decision-making was analyzed. The variability in calcium,
      phosphorus, and PTH values would lead to a different clinical decision in 23.6%,
      41.2%, and 39.7% of different session lab values. We also investigated the
      variability of these lab measures over a year in these patients and found that
      the session-to-session variability was very similar to the month-to-month
      variability. The high degree of variability of these parameters has important
      implications for clinical decision-making and for implementation of pay-for
      performance measures.

PMID- 19758300
TI  - Bioreactance: a new tool for cardiac output and thoracic fluid content monitoring
      during hemodialysis.
AB  - Outpatient hemodialysis therapy (HD) can be associated with hemodynamic
      compromise. Bioreactance has recently been shown to provide accurate,
      noninvasive, continuous, measurements of cardiac output (CO) and thoracic
      impedance (Zo) from which thoracic fluid content (TFC) can be derived assuming
      TFC=1000/Zo. This study was designed to evaluate the changes in TFC in comparison
      with the traditional indices of fluid removal (FR) and to understand the trends
      in CO changes in HD patients. Minute-by-minute changes in TFC and CO were
      prospectively collected using the bioreactance system (NICOM) in HD patients of a
      single unit. Changes in body weight (DeltaW), hematocrit (DeltaHct), and amount
      of FR were also measured. Twenty-five patients (age 77 +/- 11 years) were
      included. The TFC decreased in all patients by an average of 5.4 +/- 7.9 kohm(
      1), weight decreased by 1.48 +/- 0.98 kg, and FR averaged 2.07 +/- 1.93 L over a
      3- to 4-hour HD session. There were good correlations between DeltaTFC and DeltaW
      (R=0.80, P<0.0001) and FR (R=0.85, P<0.0001). DeltaHct (4.13 +/- 3.42%) was
      poorly correlated with DeltaTFC (R=0.35, P=0.12) and FR (R=0.40, P=0.07). The
      regression line between FR and TFC yielded FR=1.0024-0.1985TFC; thus, a 1 kohm(
      1) change of Zo correlates with an approximately 200 mL change in total body
      water. The change in CO (-0.52 +/- 0.49 L/min m(2)) during HD did not correlate
      with FR (R=0.15, P=NS). Changes in TFC represented the monitored variable most
      closely related to FR. CO remained fairly constant in this stable patient cohort.
      Further studies in high-risk patients are warranted to understand whether TFC and
      CO monitoring can improve HD session management.

PMID- 19758301
TI  - Higher arteriovenous fistulae blood flows are associated with a lower level of
      dialysis-induced cardiac injury.
AB  - Native arteriovenous fistulae (AVF) remain the vascular access of choice for
      hemodialysis (HD). Despite being associated with superior long-term outcomes (cf.
      catheter use), little is known about the systemic hemodynamic consequences of
      AVFs. Repetitive myocardial injury (myocardial stunning) is an under-recognized
      common consequence of HD. The aim of this study was to examine the impact of AVF
      flow (Qa) on dialysis-induced cardiac injury. We studied 50 chronic HD patients.
      All patients underwent echocardiography (and subsequent quantitative offline
      analysis) at baseline, during and post dialysis, to assess left ventricular
      function and the development of regional wall motion abnormalities. Qa was
      measured using ionic dialysance. Patients were divided into Qa tertiles (<500,
      mean 291+/-101 mL/min, 500-1000, mean 739+/-130 mL/min and >1000, mean 1265+/-221
      mL/min). There were no significant differences between the groups in terms of
      age, sex, diabetes, or resting ejection fraction. Patients with Qa>1000 mL/min
      had a lower prevalence of left ventricular hypertrophy (55% vs. 76%, P=0.01).
      Dialysis-induced myocardial stunning (seen in 65% of the patients studied) was
      significantly and sequentially reduced in those patients with higher Qas. This
      was seen in a lower number of segments and ventricular regions developing
      regional wall motion abnormalities, as well as a significantly reduced mean and
      cumulative percentage reduction in fractional shortening of those ventricular
      segments affected (-187+/-37%, -161+/-26%, and -101+/-25%, respectively, P=0.04).
      Relatively higher AVF flows appear to be associated with a lower level of
      observed HD-induced cardiac injury.

PMID- 19758302
TI  - Complementary parameter for dialysis monitoring based on UV absorbance.
AB  - An optical on-line monitoring system aimed at the estimation of dialysis dose has
      been tested clinically. The natural logarithmic slope is used to calculate
      Kt/V(urea) from ultraviolet (UV)-absorbance measurements. Errors in the
      calculation of Kt/V(urea) may appear due to changes in blood and dialysate flow
      or due to disturbances when the slope is used to estimate dialysis dose. This
      study introduces a new parameter for dialysis monitoring that may be used as a
      complementary parameter, the area under UV-absorbance curve (AUCa), to reflect a
      total solute removal during dialysis. The aim was to investigate the relationship
      between this new dialysis on-line monitoring parameter, AUCa, and the total
      removal of a few solutes. Fifteen patients were monitored during hemodialysis
      using UV absorbance at the wavelength of 297 nm. All spent dialysate passed
      through a flow cuvette in a spectrophotometer and then further to a collection
      tank where solute concentrations in the entire spent dialysate were determined.
      The AUCa at 297 nm was compared with the total amount of removed solute in the
      tank (reference method). The result shows strong correlations between AUCa and
      the total removal of urea, urate, creatinine, and phosphate during a given
      treatment and less strong correlation in all 15 patients together. A first
      indication of a new, possible, complementary parameter in hemodialysis treatment
      is presented, the AUCa, prospected to estimate solute removal.

PMID- 19758303
TI  - Streptococcus bovis bacteremia related to colon adenoma in a chronic hemodialysis
      patient.
AB  - Abstract We report the case of a 54-year-old hemodialysis patient who presented
      with recurrent fever due to Streptococcus bovis bacteremia related to colonic
      tubulovillous adenoma. Following polypectomy and broad-spectrum antibiotic
      therapy, the patient totally recovered. In this paper, we discussed the relation
      between S. bovis bacteremia, colonic adenomas, and hemodialysis. Awareness of
      this association is critical for early diagnosis and management.

PMID- 19758304
TI  - Hemodialysis access at initiation in the United States, 2005 to 2007: still
      "catheter first".
AB  - Despite the broad consensus that native arteriovenous fistula is the access of
      choice for hemodialysis, national-level information about vascular access at
      dialysis initiation has been unavailable in the United States. For incident
      hemodialysis patients, June 2005 to October 2007 (n=220,157), vascular access
      type was determined from the new Centers for Medicare & Medicaid Services Medical
      Evidence Report (form CMS-2728). Proportions with each type at first dialysis,
      demographic and clinical associations of each type, and associations between
      initial access type and survival were assessed. The mean patient age was 63.6
      years; 29.4% of patients were African American, and for 44.5%, end-stage renal
      disease was due to diabetes. Vascular access proportions were: fistula, 13.2% of
      patients; graft, 4.3%; catheter/maturing fistula, 16.0%; catheter/maturing graft,
      3.3%; and catheter alone, 63.2%. Adjusted odds ratios (vs. fistula) of catheter
      use alone were > or = 1.50 for lack of insurance (1.62 [95% confidence interval
      1.62-1.68]), nephrologist care for 0 to 12 months (2.75 [2.69-2.81]), other (2.19
      [2.09-2.29]), or unknown (1.53 [1.44-1.63]) cause of renal disease, institutional
      residence (1.51 [1.45-1.57]), and 7 of 18 end-stage renal disease networks. Over
      a mean follow-up of 1 year, 26.0% of the study population died. Compared with
      fistula, adjusted mortality hazards ratios were 1.39 (1.32-1.47) for grafts, 1.49
      (1.44-1.55) for catheters/maturing fistulas, 1.74 (1.65-1.84) for
      catheters/maturing grafts, and 2.18 (2.11-2.26) for catheters alone. While
      geographic variability is pronounced, vascular access at dialysis inception is
      typically suboptimal; suboptimal access exhibits a graded association with
      mortality. Lack of timely access to specialty care appears to limit optimal
      access.

PMID- 19758305
TI  - Renal dysfunction due to leukemic infiltration of kidneys in a case of chronic
      lymphocytic leukemia.
AB  - Renal failure due to leukemic infiltration of kidney in chronic lymphocytic
      leukemia is an extremely rare condition. The authors report a case of a 59-year
      old white female, with a past medical history of chronic lymphocytic leukemia
      (CLL) with 2 years of evolution without medical therapy, admitted with
      nonoliguric acute renal failure needing dialysis. Renal biopsy showed extensive
      small lymphocytes' infiltration in the cortical interstitium by CLL cells.
      Cyclophosphamide and prednisolone were started and 1 month later changed to
      fludarabine plus cyclophosphamide with improvement of renal function. Although
      renal failure due to leukemic infiltration has been described in many cases of
      acute leukemia, only 11 cases of renal failure due to CLL cells' infiltration
      have been described in the literature. Renal histology is an extremely important
      tool to confirm diagnosis.

PMID- 19758306
TI  - Reproductive senescence in a cooperatively breeding mammal.
AB  - 1. Senescence (or 'ageing') is a widespread and important process in wild animal
      populations, but variation in ageing patterns within and between species is
      poorly understood. 2. In cooperatively breeding species, the costs of
      reproduction are shared between breeders and one or more helpers. The effects of
      ageing in breeders may therefore be moderated by the presence of helpers, but
      there have been very few studies of senescence patterns in natural populations of
      cooperative breeders. 3. Here, we use 13 years of data from a long-term study
      population of wild meerkats (Suricata suricatta) to investigate age-related
      changes in several traits known to be key components of reproductive success in
      females of this species. 4. Four of the six traits studied exhibited significant
      declines with age, indicating senescence. Litter size, the number of litters
      produced per year and the number of pups that survived to emergence from the
      natal burrow per year all increased with female age up to a peak at c. 4 years,
      and declined steeply thereafter; the mean pup weight at emergence in a given
      litter declined steadily from age zero. 5. These results provide the first
      evidence of reproductive senescence in a wild population of a cooperatively
      breeding vertebrate. Breeding success declined with age despite the sharing of
      reproductive costs in this species, but further study is needed to investigate
      whether helping affects other aspects of senescence, including survival.

PMID- 19758307
TI  - Determinants of factor VIII plasma levels in carriers of haemophilia A and in
      control women.
AB  - Factor VIII (FVIII) levels show a considerable variability in female carriers of
      haemophilia A. Presently, the reasons for this are poorly understood. The aim of
      the study was to elucidate the influence of genetic and non-genetic parameters on
      FVIII plasma levels in carriers (n = 42). Results were compared with age-matched
      healthy women without carriership of haemophilia A (n = 42). Each carrier was
      tested for the family-specific mutation, ABO blood group, FVIII level, von
      Willebrand factor (VWF) antigen and activity and C-reactive protein (CRP). FVIII
      levels were lower in carriers compared to non-carriers [74% (51-103) vs. 142%
      (109-169), P < 0.001]. No statistically significant differences were observed
      between the two groups with respect to VWF activity, prothrombin-time, hs-CRP,
      fibrinogen, body mass index (BMI), age and smoking status as well as the
      distribution of ABO blood groups. In non-carriers, FVIII was statistically
      significantly correlated with BMI, activated partial thromboplastin time (APTT),
      VWF antigen, hs-CRP and fibrinogen. In carriers, significant correlations between
      FVIII and APTT, VWF antigen and activity were found, whereas BMI, hs-CRP or
      fibrinogen did not correlate with FVIII. In non-carriers, the association of
      FVIII with ABO blood groups was statistically significant (P = 0.006), but not in
      carriers of haemophilia A (P = 0.234). The type of FVIII gene mutation did not
      influence FVIII levels. Carrier status is the major determinant of a carrier;s
      FVIII plasma level. Factors known to influence FVIII levels in the general
      population do not significantly affect FVIII activity in carriers, neither does
      the type of mutation influence FVIII levels.

PMID- 19758308
TI  - Development, implementation and evaluation of a new self-help programme for
      mothers of haemophilic children in Korea: a pilot study.
AB  - Developing an effective support group programme is necessary to help the mothers
      of haemophilic children to encourage their children to live healthily and
      independently through early management, as well as to reduce the mothers'
      depression and stress. Although the need is high, there is no self-help group
      programme for mothers in Korea yet.The purpose of this study was to develop,
      implement and evaluate a new self-help group programme for mothers of children
      with haemophilia. Pre-experimental design was used to evaluate the effect of a
      pilot group. Participants were 12 mothers of haemophilic children below 15 years
      old. Knowledge on haemophilia, self-efficacy, depression, rearing stress and
      quality of life were evaluated using questionnaires. A Wilcoxon signed rank test
      was used to compare pre- and post-test.Knowledge, self-efficacy and quality of
      life were significantly increased, while depression was statistically reduced
      after the programme. The rearing stress was also reduced, but the result was not
      statistically significant.The self-help programme for mothers of haemophilic
      children increased the mothers' knowledge of haemophilia, self-efficacy and
      quality of life, while decreasing their depression symptoms. It seems that the
      programme was effective, but additional experimental study is necessary to verify
      the effects of the programme.

PMID- 19758309
TI  - Current challenges of pharmacovigilance in bleeding disorders: converting the
      burden to benefit.
AB  - SUMMARY: Safety surveillance studies have proven essential in research and
      development of new biological therapies for bleeding disorders as well as other
      diseases. Although product safety regarding HIV, hepatitis, and other blood-borne
      infections is currently excellent, potential new infectious agents require
      continued vigilant monitoring. Inhibitor development is the most common serious
      side effect of haemophilia replacement therapy. Several aetiological factors
      associated with inhibitors have been identified, but their true impact is still
      largely unknown. Moreover, whether plasma-derived and recombinant factor products
      differ in their immunogenic profiles is an unresolved issue. Coagulation factor
      products under development and those currently on the market require uniform,
      long-term surveillance. The European Haemophilia Safety Surveillance (EUHASS)
      project was recently established to meet these goals. The pharmaceutical industry
      and clinicians face common challenges complying with these requirements. In rare
      diseases like haemophilia, obtaining adequate patient numbers poses a challenge.
      Another challenge is a lack of methods for assessing disease severity, a
      surprising deficiency in the era of modern medical and laboratory technology.
      National and international registries can be used to gather required safety
      surveillance information. Simultaneously, clinicians benefit from well-organized
      registry data in their daily practice and harmonize the quality of comprehensive
      haemophilia care by homogeneous follow-up platforms. Experience with such
      registries comes, for example, from Europe (PEDNET), the USA (CDC/UDC), the UK
      (UKHCDO), and Sweden (Malmo). It is important to commit to future
      pharmacovigilance efforts, aiming at high-quality safety surveillance programmes
      at both the pharmaceutical research community and clinical levels.

PMID- 19758310
TI  - Effects of Sp1 overexpression on cultured human corneal stromal cells.
AB  - Sp1, a transcription factor, is upregulated in keratoconus, a cornea-thinning
      disease. Keratoconus corneas have also been shown to contain increased levels of
      degradative enzymes such as cathepsin B and decreased proteinase inhibitors such
      as alpha1-proteinase inhibitor (alpha1-PI). We transfected cultured human corneal
      stromal cells to overexpress Sp1. The resulting effects on cathepsin B and alpha1
      PI levels as well as the cellular proliferative and apoptotic activities were
      examined by Western blotting and cytochemical staining. It was found that the Sp1
      transfected cells contained a greater amount of cathepsin B than did mock
      transfected controls. The activity of cathepsin B was also increased. By
      contrast, the protein level of alpha1-PI was lowered in corneal stromal cells
      upon Sp1 overexpression. The Sp1-induced alterations thus mimicked closely those
      observed in keratoconus, supporting the notion that Sp1 upregulation may be a key
      factor contributing directly to the disease development. Furthermore, the
      apoptotic activity was unaffected in Sp1 transfectants but the proliferation was
      inhibited, consistent with the idea that Sp1 may play a role in differentiation
      of corneal cells.

PMID- 19758311
TI  - Detection of a rare Caucasoid HLA-DRB1*0337 in a Taiwanese bone marrow donor
      using sequence-based typing method.
AB  - We here describe the identification of HLA-DRB1*0337, using sequence-based typing
      (SBT) method, in a Taiwanese bone marrow donor intrigued by a casual curiosity on
      the donor's racial background. On high-resolution sequence-specific primer (SSP)
      typing we observed misleading reaction patterns due to similarity of DNA
      sequences in the exon 2 of DRB1*0301, *0317, *0337 and *1139. When encountering
      rare alleles in HLA typing, it is important to pay extra attentions to avoid
      pitfalls and shortcomings of SSP typing kits routinely used and bear in mind that
      constant up-dating of high-resolution SSP typing kits to be able to distinguish
      newly reported alleles. SBT may be considered as a back-up HLA typing method to
      confirm rare alleles.

PMID- 19758312
TI  - A unique display of toll-like receptor 4 Asp299Gly and Thr399Ile polymorphisms in
      non-Han Chinese Hani population.
AB  - The toll-like receptor 4 (TLR4) polymorphisms, Asp299Gly and Thr399Ile, were
      investigated with PCR-RFLP and DNA sequencing methods in 938 and 980 individuals
      from the Yunnan Hani ethnic minority and the majority Han population,
      respectively. Six heterozygotes for both Asp299Gly and Thr399Ile were detected in
      the Hani, a polymorphism frequency of 0.6397%, whereas no variants were found
      amongst the Han.

PMID- 19758313
TI  - Tyrosine kinase 2 and interferon regulatory factor 5 polymorphisms are associated
      with discoid and subacute cutaneous lupus erythematosus.
AB  - Lupus erythematosus (LE) is a heterogeneous disease ranging from skin-restricted
      manifestations to a progressive multisystem disease. The specific skin lesions
      include chronic cutaneous, subacute cutaneous and acute cutaneous LE. Both
      genetic and environmental factors are involved in the development of LE. However,
      reports on the genetic background of cutaneous lupus erythematosus (CLE) forms,
      namely discoid (DLE) and subacute cutaneous lupus erythematosus (SCLE), are
      sparse. We investigated whether the known systemic LE (SLE) susceptibility genes
      also predispose to CLE. Altogether, 219 Finnish patients with DLE or SCLE and 356
      healthy controls were recruited. Single nucleotide polymorphisms tagging reported
      risk genes were genotyped. Tyrosine kinase 2 (TYK2) rs2304256 was associated with
      increased risk of DLE (P = 0.012, OR = 1.47, 95% CI = 1.01-1.98). Expression of
      TYK2 was demonstrated by immunohistochemistry in macrophage-like cells and
      neutrophils and interferon regulatory factor 5 (IRF5) in macrophage- and
      fibroblast-like cells of DLE, SCLE and SLE skin. IRF5 rs10954213 showed
      association with DLE (P = 0.017, OR = 1.40, 95% CI = 1.06-1.86) and SCLE (P =
      0.022, OR = 1.87, 95% CI = 1.09-3.21). A haplotype of cytotoxic T-lymphocyte
      associated protein 4 (CTLA4) showed association with DLE (P = 0.0065, OR = 2.51,
      95% CI = 1.25-5.04). Our results show that the TYK2, IRF5 and CTLA4 genes
      previously associated with SLE also confer risk for DLE and SCLE, suggesting that
      different LE subphenotypes may share pathogenetic pathways.

PMID- 19758314
TI  - Tumor necrosis factor-alpha processing inhibitor-1 inhibits skin fibrosis in a
      bleomycin-induced murine model of scleroderma.
AB  - Elevated serum concentration of soluble tumor necrosis factor receptor p55
      (sTNFRp55) is known to correlate with the severity of systemic sclerosis (SSc).
      However, it has not been verified whether this increase contributes to the
      pathogenesis of SSc. In this study, we found that sTNFRp55 also is increased in
      the bleomycin (BLM)-induced murine model of SSc. Therefore, we examined the
      effect of tumor necrosis factor-alpha processing inhibitor-1 (TAPI-1), the
      inhibitor of TNFRp55 sheddase, in this model. TAPI-1 was administered weekly to
      mice with skin fibrosis induced by daily BLM injections. TAPI-1 significantly
      suppressed BLM-induced skin thickness and the number of myofibroblasts. It also
      inhibited the increase of serum sTNFRp55 after 3 weeks of BLM injections. The
      mRNA expression of collagen type I alpha1, transforming growth factor-beta1 and
      alpha smooth muscle actin were decreased by TAPI-1 administration. Taken
      together, these findings indicate that targeting the TNFalpha converting enzyme
      might be a new type of therapy for patients with SSc.

PMID- 19758315
TI  - Signal transducer and activator of transcription 3 upregulates interleukin-8
      expression at the level of transcription in human melanoma cells.
AB  - Many melanoma cells continuously produce interleukin-8 (IL-8). The involvement of
      signal transducer and activator of transcription 3 (STAT3) in the constant
      production of IL-8 in melanoma cells was examined. The level of IL-8 production
      correlated well with that of the phosphorylated (activated) STAT3 in six human
      melanoma cell lines. Introduction of the constitutively activated form of STAT3
      (STAT3-C) into WM35 melanoma cells, that show low levels of IL-8 and
      phosphorylated STAT3, enhanced IL-8 production. Knockdown of STAT3 suppressed IL
      8 production in WM1205Lu cells that contain a high level of IL-8 accompanied by
      STAT3 phosphorylation. Introduction of STAT3-C markedly increased the luciferase
      activity in WM1205Lu cells transfected with reporter vectors linked to the 5'
      flanking region of the IL-8 gene from -546 to +44 base pair (bp) and from -272 to
      +44 bp, but not in cells expressing reporter plasmids from -133 to +44 bp and
      from -98 to +44 bp. These results indicate that the upregulation of IL-8
      production is caused by constitutive STAT3 activation at the level of gene
      transcription in melanoma cells.

PMID- 19758316
TI  - CC chemokines as potential immunologic markers correlated with clinical
      improvement of atopic dermatitis patients by immunotherapy.
AB  - Although immunotherapy is not accepted as a curative treatment for atopic
      dermatitis (AD), most studies have shown positive effects of immunotherapy on AD
      patients. The serum levels of CC chemokine ligand 17 (CCL17), CCL22 and CCL18
      have been reported to be highly correlated with disease severity, which suggests
      important roles for CC chemokines in the pathogenesis of AD. OBJECTIVE: The
      purpose of this study was to investigate the changes in clinical and immunologic
      markers before and after immunotherapy and to find which CC chemokines correlate
      with clinical improvement after immunotherapy with house dust mite (HDM)
      allergens in AD patients. METHODS AND RESULTS: A total of 20 AD patients who were
      sensitized to HDM allergens through a skin-prick test and Pharmacia CAP system
      were treated with subcutaneous immunotherapy using HDM allergens (treatment
      duration 12-60 months). Eczema area and severity index scores in 20 patients with
      AD decreased significantly after immunotherapy (P < 0.001). Serum total
      immunoglobulin E (IgE) and Dermatophagoides pteronyssinus-specific IgE levels
      tended to decrease after treatment although this was not statistically
      significant, and the D. farinae-specific IgE level showed no change. Serum CCL17,
      CCL22 and CCL18 levels decreased significantly from baseline after treatment (P =
      0.043, 0.017 and <0.001, respectively). The percentage reductions in serum CCL17
      and CCL22 level were significantly correlated with reductions in disease severity
      (P = 0.007, R(2) = 0.301 and P = 0.037, R(2) = 0.177, respectively). CONCLUSION:
      We suggest that CCL17 and CCL22 are good immunological marker candidates that can
      be used to assess clinical improvement after immunotherapy in AD patients.

PMID- 19758317
TI  - Increased subcutaneous adipose tissue impairs dermal function in diet-induced
      obese mice.
AB  - Increment of subcutaneous adipose tissue is a risk factor for facial
      morphological changes, such as sagging, which may be at least partly because of
      the increased weight burden of accumulated fat. However, it is not clear how the
      increase of subcutaneous adipose tissue affects dermal structure and function. We
      examined this issue in HR-1 hairless mice given a high-fat diet (HFD). After
      having been fed with HFD for 12 weeks, the mice became obese and the subcutaneous
      adipose tissue layer was significantly thickened, while the dermal layer became
      significantly thinner than that of control mice fed normal diet. However, the
      thickness of the dermal layer was not changed in the ear pinna, which lacks a
      subcutaneous adipose layer, suggesting that increase of subcutaneous adipose
      tissue may induce dermal changes. The number of dermal fibroblasts in the dermis
      was significantly reduced in obese mice, although there was no change in gene
      expression levels of extracellular matrix components, including collagen,
      hyaluronic acid synthase, fibulin5, fibrillin-1, laminin beta1, matrix
      metalloproteinases and tissue inhibitor of metalloproteinases. Dermal elasticity
      was significantly decreased in obese hairless mice. These results suggest that
      subcutaneous adipose cells in obese mice may reduce the proliferation of dermal
      fibroblasts and induce a decrease of dermal thickness and elasticity. Therefore,
      the increment of the subcutaneous adipose layer in obese subjects may induce
      impairment of dermal biomechanical characteristics and promote the appearance of
      sagging.

PMID- 19758318
TI  - Human mast cells express androgen receptors but treatment with testosterone
      exerts no influence on IgE-independent mast cell degranulation elicited by
      neuromuscular blocking agents.
AB  - Women predominate in the anaphylactic reactions to neuromuscular blocking agents
      (NMBA). The expression of oestrogen receptors has been demonstrated in mast cells
      and oestrogen treatment can enhance mast cell degranulation, but the influence of
      androgens remains largely unclear. Our immunocytochemical study showed the
      expression of androgen receptor (AR) in mast cells isolated from human foreskin
      as well as in two human mast cell lines, HMC-1 and LAD2. The amount of AR was
      most abundant in human skin mast cells as determined by real-time polymerase
      chain reaction analysis. Treatment of the HMC-1 mast cells with testosterone or
      17beta-oestradiol, alone or in combination with different NMBA, did not affect
      mast cell degranulation as measured by the release of beta-hexosaminidase. Our
      study shows for the first time the expression of AR in human skin mast cells.
      Further studies using primary human mast cell cultures are needed to understand
      whether and how sex hormones can influence mast cell activation.

PMID- 19758319
TI  - IL-6 stimulates but is not essential for stratum corneum formation and
      permeability barrier development during gestation.
AB  - The regulation of epidermal ontogenesis is a complex process. Previous studies
      have shown that cytokines (IL-1, TNFalpha and IL-6) regulate permeability barrier
      homeostasis in adult mice. Recently, we reported that IL-1 and TNFalpha
      accelerate stratum corneum (SC) formation and permeability barrier development in
      foetal rodents. Here, we determined whether IL-6 also regulates SC formation and
      permeability barrier development during late gestation. Using a rat skin explant
      model, we demonstrated that IL-6 accelerates permeability barrier formation in a
      time- and dose-dependent fashion. This acceleration of barrier formation is
      attributable to (a) accelerated lamellar membrane maturation, (b) formation of a
      multi-layer SC and (c) enhanced expression of epidermal differentiation markers.
      When comparing epidermis of IL-6-deficient (knockout mice) and wild-type foetal
      mice at days 16-18, we could not detect any abnormalities in either SC formation
      or the expression of differentiation markers in knockout (KO) mice. In parallel,
      the basal expression levels of IL-6 mRNA in epidermis and IL-6 protein in
      amniotic fluid were very low, with only a minimal change in IL-6 receptor mRNA
      levels in epidermis of days 16-22 foetal mice. These low IL-6 levels may account,
      at least in part, for the absence of epidermal abnormalities in IL-6 KO mice. In
      conclusion, exogenous IL-6 accelerates epidermal ontogenesis, but it is not
      essential for normal epidermal maturation.

PMID- 19758320
TI  - Long-term efficacy of etanercept in hidradenitis suppurativa: results from an
      open-label phase II prospective trial.
AB  - OBJECTIVE: To evaluate the long-term efficacy of etanercept for the management of
      hidradenitis suppurativa. METHODS: Analysis was based on the long-term follow-up
      (weeks 24-144) of 10 patients enrolled in a prospective open-label phase II
      study; etanercept was initially administered subcutaneously 50 mg once weekly for
      12 weeks in 10 patients. Disease recurrence and the need to restart etanercept
      were recorded. RESULTS: Three patients did not report any disease recurrence. A
      second course of treatment with etanercept was needed in seven patients.
      Favourable responses were found in five; two patients failed treatment.
      CONCLUSIONS: The first treatment course achieved long-term disease remission in
      almost one-third of patients. The remaining needed a second treatment course but
      even in that case, their disease severity at restart was significantly lower
      compared with baseline.

PMID- 19758321
TI  - In vivo and in vitro evidence for epidermal H2O2-mediated oxidative stress in
      piebaldism.
AB  - Piebaldism is characterised by the absence of pigment in patches on the skin,
      usually present at birth. Mutations in the kit gene are documented. Clinically
      this disorder can mimic vitiligo. Here, we show for the first time the presence
      of oxidised pteridine-induced fluorescence in association with H2O2-mediated
      stress in piebald patches employing Wood's light and in vivo FT-Raman
      spectroscopy. In situ immunofluorescence data revealed low catalase and
      methionine sulphoxide reductase A (MSRA) levels whereas thioredoxin reductase and
      methionine sulphoxide reductase B (MSRB) are not affected. We also show low
      superoxide dismutase levels in these patients. The presence of thioredoxin
      reductase provides capacity to reduce H2O2, a mechanism which is absent in
      vitiligo. Importantly, this enzyme reduces biopterin back to the functioning
      cofactor 6-tetrahydrobiopterin. The absence of MSRA indicates deficient
      methionine sulphoxide repair in the cytosol, meanwhile the presence of MSRB is
      helpful to protect the nucleus. Taken together, we have identified H2O2-mediated
      stress in piebald skin with distinct differences to vitiligo.

PMID- 19758322
TI  - Activation of toll-like receptors 2, 3 or 5 induces matrix metalloproteinase-1
      and -9 expression with the involvement of MAPKs and NF-kappaB in human epidermal
      keratinocytes.
AB  - Toll-like receptors (TLRs) on epidermal keratinocytes are the first line of
      defense against microbe invasion, and matrix metalloproteases (MMPs) regulate
      inflammation, cell migration and wound healing. In this study, we demonstrate
      that the mRNA and protein expressions of MMP-1 and MMP-9 in human epidermal
      keratinocytes are induced by ligands for TLR2, TLR3 and TLR5 [Pam3CSK4, Poly(I:C)
      and flagellin, respectively] in a dose-dependent manner. We also found that the
      ligands for TLR2, TLR3 and TLR5 activate the MAP kinases, JNK and p38 MAPK, but
      not ERK1/2. Furthermore, treatment with the ligands for TLR2, TLR3 and TLR5 also
      induced the degradation of IkappaB-alpha and activated the nuclear translocation
      of NF-kappaB. MMP-1 induction by the ligands for TLR2, TLR3 and TLR5 was
      inhibited by pretreatment with BAY11-7082 (NF-kappaB inhibitor) or SP600125 (JNK
      inhibitor), whereas MMP-9 expression was inhibited by pretreatment with BAY11
      7082, SP600125 or SB203580. These findings demonstrate that the activation of
      TLR2, TLR3 or TLR5 induces the expression of MMP-1 and MMP-9 in human epidermal
      keratinocytes. In addition, NF-kappaB or JNK mediated the MMP-1 expression
      induced by TLR2, TLR3 and TLR5, whereas NF-kappaB, JNK or p38 MAPK mediated the
      MMP-9 expression induced by TLR2, TLR3 and TLR5.

PMID- 19758323
TI  - Efficacy of quantifying melanosome transfer with flow cytometry in a human
      melanocyte-HaCaT keratinocyte co-culture system in vitro.
AB  - In this study, we describe a simple, specific, reproducible and quantitative
      assay system to assess melanosome transfer. We first established a co-culture
      model of normal human epidermal melanocytes and HaCaT keratinocytes. The cells
      were co-cultured for 72 h in a serum-free keratinocyte growth media and double
      labelled with Fluorescein isothiocyanate (FITC)-conjugated antibody against the
      melanosome-specific protein gp100, and with Phycoerythrin (PE)-conjugated
      antibody against the keratinocyte-specific marker cytokeratin. Then, the cells
      were examined using co-focal microscope and flow cytometry. The increased
      melanosome transfer from melanocytes to HaCaT keratinocytes was observed in a
      time-dependent manner. To verify the accessibility of this method, two known
      melanosome transfer inhibitors and two known melanosome transfer stimulators were
      applied. Consistent with previous investigation, soybean trypsin inhibitor (STI),
      niacinamide inhibited melanosome transfer, alpha-melanocyte stimulating hormone
      (alpha-MSH) and keratinocyte growth factor (KGF) increased melanosome transfer,
      respectively, in a dose-dependent manner. The model used in this study could thus
      represent a rapid and reliable tool to identify modulators of human melanosome
      transfer.

PMID- 19758324
TI  - Topical calcitriol protects from UV-induced genetic damage but suppresses
      cutaneous immunity in humans.
AB  - Calcitriol, the biologically active form of vitamin D, has been reported to cause
      both suppressive and protective immune effects in mice. Its immune effects in
      vivo in humans are unclear. We investigated the in vivo effects of topical
      calcitriol on minimal erythema dose and skin immune responses in healthy
      volunteers. We found that calcitriol did not protect from ultraviolet (UV)
      induced erythema (sunburn) when applied either 24 h before or immediately after
      irradiation, although it decreased the density of sunburn cells and thymine
      dimers seen on biopsy when applied 24 h before and again immediately after
      irradiation. Using the Mantoux reaction as a model of skin immunity, we found
      that topical calcitriol applied at high total doses reduced the Mantoux responses
      of nearby untreated, unirradiated skin, suggesting a para-local or systemic
      immunosuppressive effect not observed with lower calcitriol doses. We then
      measured UV-induced suppression of Mantoux reactions at vehicle-treated sites and
      sites treated with low-dose calcitriol, and found that calcitriol neither reduced
      nor enhanced UV-induced immunosuppression. Despite calcitriol reducing UV-induced
      DNA damage, which should protect the immune system, it has immunosuppressive
      effects in our model which may help to explain the efficacy of analogues such as
      calcipotriol in the treatment of psoriasis.

PMID- 19758325
TI  - Intracellular delivery of major histocompatibility complex class I-binding
      epitopes: dendritic cells loaded and matured with cationic peptide/poly(I:C)
      complexes efficiently activate T cells.
AB  - Based on their role for the induction of T-cell responses, dendritic cells (DCs)
      are popular candidates in cancer vaccine development. We established a novel
      single-step intracellular delivery of peptide/poly(I:C) complexes for antigen
      loading and Toll-like receptor-3 (TLR3)-mediated maturation of human DCs using a
      cell-penetrating peptide (tat(49-57): RKKRRQRRR) as delivery vector. Towards this
      end, a cationic tat-sequence was fused with an antigenic, major
      histocompatibility complex (MHC) class I-binding melanoma epitope (Melan-A/Mart-1
      sequence: ELAGIGILTV) and then mixed with negatively charged poly(I:C) dsRNA to
      form peptide/nucleic acid complexes. Flow cytometry and confocal laser scanning
      microscopy confirmed intracellular localization of TLR3 in monocyte-derived
      immature DCs (iDCs). Peptide/poly(I:C) complexes were readily internalized by
      iDCs without negatively affecting cell viability. They induced DC maturation and
      secretion of bioactive interleukin (IL)-12p70. When peptide/poly(I:C) complex
      loaded DCs were used for autologous T cell stimulation, epitope-specific
      interferon-gamma secretion was quantitatively superior in comparison to peptide
      loaded DCs matured by a cytokine cocktail, as detected by enzyme-linked
      immunospot assays. Thus, complexes of cationic antigenic peptides and poly(I:C)
      might be of great utility for a TLR3-mediated DC maturation and intracellular
      peptide targeting in a single step. Resulting DCs induce a strong
      expansion/activation of antigen-specific T cells in the context of an IL-12p70
      secretion.

PMID- 19758326
TI  - Screening of lactic acid bacteria from Indonesia reveals glucansucrase and
      fructansucrase genes in two different Weissella confusa strains from soya.
AB  - Homopolysaccharide (glucan and fructan) synthesis from sucrose by sucrase enzymes
      in lactic acid bacteria (LAB) has been well studied in the genera Leuconostoc,
      Streptococcus and Lactobacillus. This study aimed to identify and characterize
      genes encoding glucansucrase/glucosyltransferase (GTF) and
      fructansucrases/fructosyltransferase (FTF) enzymes from genomic DNA of 'rare'
      Indonesian exopolysaccharide-producing LAB. From a total of 63 exopolysaccharide
      producing LAB isolates obtained from foods, beverages and environmental samples,
      18 isolates showing the most slimy and mucoid colony morphologies on sucrose were
      chosen for further study. By comparing bacterial growth on De Man, Rogosa and
      Sharpe (MRS)-sucrose with that on MRS-raffinose, and using the results of a
      previous PCR screening study with degenerate primer pairs targeting the conserved
      catalytic domain of GTFs, various strains were identified as producers of fructan
      (13), of glucan only (five) or as potential producers of both glucan and fructan
      (nine). Here, we report the characteristics of three gtf genes and one ftf gene
      obtained from Weissella confusa strains MBF8-1 and MBF8-2. Strain MBF8-1 harbored
      two putative gtf genes with high sequence similarity to GTFB of Lactobacillus
      reuteri 121 and GTF180 of L. reuteri 180, respectively. Strain MBF8-2 possessed
      single gtf and ftf genes with high sequence similarity to GTFKg3 of Lactobacillus
      fermentum Kg3 and DSRWC of Weissella cibaria, and FTF levansucrase of L. reuteri
      121, respectively.

PMID- 19758327
TI  - Tyrosine 9 is the key amino acid in microcin J25 superoxide overproduction.
AB  - Escherichia coli microcin J25 (MccJ25) is a lasso-peptide antibiotic comprising
      21 L-amino acid residues (G(1)-G-A-G-H(5)-V-P-E-Y-F(10)-V-G-I-G-T(15)-P-I-S-F
      Y(20)-G). MccJ25 has two independent substrates: RNA-polymerase (RNAP) and the
      membrane respiratory chain. The latter is mediated by oxygen consumption
      inhibition together with an increase of superoxide production. In the present
      paper, the antibiotic MccJ25 was engineered by substituting Tyr(9) or Tyr(20)
      with phenylalanine. Both mutants were well transported into the cells and
      remained active on RNAP. Only the Y9F mutant lost the ability to overproduce
      superoxide and inhibit oxygen consumption. The last results confirm that the
      Tyr(9), and not Tyr(20), is involved in the MccJ25 action on the respiratory
      chain target.

PMID- 19758328
TI  - Cloning, prokaryotic expression, and bioactivity of the calmodulin gene of
      Magnaporthe grisea.
AB  - The cDNA encoding the calmodulin (CaM) protein was isolated from the mycelia of
      Magnaporthe grisea PO-041 strain by reverse transcriptase (RT)-PCR and named
      MgCaM. High similarities in sequence to other reported CaMs suggested that CaM is
      highly conserved. The MgCaM gene was expressed in Escherichia coli BL21 using a
      pET32a(+) plasmid. MgCaM with or without a Trx tag exhibited a Ca(2+)-dependent
      electrophoretic migration shift, suggesting that the activity of MgCaM depends on
      the presence of Ca(2+). Western blot analysis showed that Trx-MgCaM possessed
      specific immunoreactivities and could be specifically recognized by an anti
      AtCaM2-Ig polyclonal antibody raised against AtCaM2 of Arabidopsis.
      Immunocytolocalization of MgCaM indicated that the number of gold particles was
      the most in germ tubes, next to conidia, followed by appressoria and the mycelia
      from liquid media, and the least in the aerial hypha from solid media. Also, in
      the germ tube, mycelium from liquid media and appressorium, the density of gold
      particles in the cell wall was markedly higher than that in the cytoplasm. In
      conidia, the number of MgCaM particles in the cytoplasm was obviously higher than
      that in the cell wall. However, in the aerial hypha, MgCaM only distributed at
      the cytoplasm and no gold particle was detected in the cell wall.

PMID- 19758330
TI  - Characterization of the proteins encoded by the Bacillus subtilis yoxA-dacC
      operon.
AB  - In Bacillus subtilis, the yoxA and dacC genes were proposed to form an operon.
      The yoxA gene was overexpressed in Escherichia coli and its product fused to a
      polyhistidine tag was purified. An aldose-1-epimerase or mutarotase activity was
      measured with the YoxA protein that we propose to rename as GalM by analogy with
      its counterpart in E. coli. The peptide D-Glu-delta-m-A(2)pm-D-Ala-m-A(2)pm-D-Ala
      mimicking the B. subtilis and E. coli interpeptide bridge was synthesized and
      incubated with the purified dacC product, the PBP4a. A clear dd-endopeptidase
      activity was obtained with this penicillin-binding protein, or PBP. The possible
      role of this class of PBP, present in almost all bacteria, is discussed.

PMID- 19758329
TI  - The type III secretion system is involved in the invasion and intracellular
      survival of Escherichia coli K1 in human brain microvascular endothelial cells.
AB  - Type III secretion systems (T3SSs) have been documented in many Gram-negative
      bacteria, including enterohemorrhagic Escherichia coli. We have previously shown
      the existence of a putative T3SS in meningitis-causing E. coli K1 strains,
      referred to as E. coli type III secretion 2 (ETT2). The sequence of ETT2 in
      meningitis-causing E. coli K1 strain EC10 (O7:K1) revealed that ETT2 comprises
      the epr, epa and eiv genes, but bears mutations, deletions and insertions. We
      constructed the EC10 mutants deleted of ETT2 or eivA gene, and their
      contributions to bacterial pathogenesis were evaluated in human brain
      microvascular endothelial cells (HBMECs). The deletion mutant of ETT2 exhibited
      defects in invasion and intracellular survival compared with the parental E. coli
      K1 strain EC10. The mutant deleted of eivA within ETT2 was also significantly
      defective in invasion and intracellular survival in HBMECs, and the defects of
      the eiv mutant were restored to the levels of the parent strain EC10 by
      transcomplementation. These findings suggest that ETT2 plays a role in the
      pathogenesis of E. coli K1 infection, including meningitis.

PMID- 19758331
TI  - Characterization of the NgoAXP: phase-variable type III restriction-modification
      system in Neisseria gonorrhoeae.
AB  - Methyltransferases associated with type III restriction-modification (RM) systems
      are phase-variably expressed in a variety of pathogenic bacteria. NgoAXP, the
      type III RM system encoded by Neisseria gonorrhoeae, was characterized in this
      study. The cloned resngoAXP and ngoAXPmod genes were expressed in Escherichia
      coli strains. The restriction and modification activities of NgoAXP were
      confirmed in vivo by the lambda phage restriction and modification test and in
      vitro by the methylation of DNA substrates in the presence of [methyl
      (3)H]AdoMet. As in all known type III systems, the restriction activity needed
      the presence of both genes, while the presence of the ngoAXPmod gene was
      sufficient for DNA methylation. Following its overexpression, the DNA
      methyltransferase M.NgoAXP was purified to apparent homogeneity using metal
      affinity chromatography. The specific sequence recognized by this enzyme was
      determined as a nonpalindromic sequence: 5'-CCACC-3', in which the adenine
      residue is methylated. We observed that in E. coli cells, the expression of the
      restriction phenotype associated with NgoAXP switched randomly. This phase
      variation was associated with the change in the number of pentanucleotide repeats
      (5'-CCAAC/G-3') present at the 5'-end of the coding region of the ngoAXPmod gene.

PMID- 19758332
TI  - Complete mitochondrial genome sequences of three Nakaseomyces species reveal
      invasion by palindromic GC clusters and considerable size expansion.
AB  - Here we report the sequence of three mitochondrial genomes from yeasts of the
      Nakaseomyces clade that includes the pathogenic yeast Candida glabrata, namely,
      that of Kluyveromyces delphensis, Candida castellii and Kluyveromyces
      bacillisporus. The gene content is equivalent to that of C. glabrata, but reveals
      the existence of new group I introns in COX1 and CYTB and new potential intronic
      endonucleases. Gene order is highly rearranged in these genomes, which contain
      numerous palindromic GC clusters. The more GC nucleotides these elements contain,
      the longer and more AT-rich are the intergenes containing them, leading to a
      direct relationship between the number of Gs and Cs within the elements and the
      size of the genomes. Thus, there is a fivefold difference in size between the
      smallest and the largest mitochondrial genome, with the largest being the most AT
      rich overall. Sequences are available under EMBL accession numbers FM995164,
      FM995165, and FM995166.

PMID- 19758333
TI  - Genetic improvement of thermo-tolerance in wine Saccharomyces cerevisiae strains
      by a backcross approach.
AB  - During red wine fermentation, high temperatures may cause stuck fermentation by
      affecting the physiology of fermenting yeast. This deleterious effect is the
      result of the complex interaction of temperature with other physicochemical
      parameters of grape juice, such as sugar and lipid content. The genetic
      background of fermenting yeast also interacts with this complex matrix and some
      strains are more resistant to high temperatures than others. Here, the
      temperature tolerance of nine commercial starters was evaluated, demonstrating
      that, at high sugar concentrations, half of them are sensitive to temperature.
      Using a classical backcross approach, one thermo-sensitive commercial starter was
      genetically improved by introducing quantitative trait loci conferring resistance
      to temperature. With this breeding program it is possible to obtain a thermo
      resistant strain sharing most of its genome with the initial commercial starter.
      The parental and improved strains were compared for population growth and
      fermentation ability in various conditions. Despite their common genetic
      background, these two strains showed slight physiological differences in response
      to environmental changes that enable identification of the key physiological
      parameters influencing stuck fermentation.

PMID- 19758334
TI  - Medicine or ecstasy? The importance of the logo.
AB  - Some pharmaceutical tablets have an appearance that resembles that of ecstasy (a
      logo and often a name referring to it, a given shape and/or a colour). These are
      sometimes sold in the street as 'ecstasy'. In order to assess the knowledge of
      this phenomenon, surveys were conducted among designer drug users (DDUsers),
      pharmacists and pharmaceutical firms. Three surveys were conducted: the first one
      was conducted among DDUsers by means of an anonymous questionnaire; the second
      one consisted of a 1-month postal survey within a network of 155 community
      pharmacies in the Aquitaine region, Southwestern France and the third one
      consisted of a postal questionnaire sent to 71 pharmaceutical firms. Nineteen
      users, 77 pharmacists and 25 pharmaceutical firms participated in the surveys.
      All DDUsers knew the existence of what they call ecstasy 'swindles', but less
      than one quarter of the pharmacists and one third of pharmaceutical firms were
      aware of the potential recreational and involuntary misuse of medicines. The
      phenomenon of 'swindle' in the illicit market is not new. However, the sale of
      medicines because of their appearance or logo seems to be quite rare. In order to
      limit this diversion, prevention should be reinforced. In addition,
      recommendations on the appearance of medicine tablets should be set up by
      regulatory agencies in charge of medicine approval.

PMID- 19758335
TI  - Association between the -159C/T CD14 gene polymorphism and tuberculosis in a
      Korean population.
AB  - The aim of the present study was to confirm the association between the CD14
      159C/T polymorphism and tuberculosis in the Korean population and to elucidate
      the functional basis for this putative association. CD14-159C/T genotypes were
      determined by PCR - restriction fragment length polymorphism analysis in 274
      tuberculosis patients and 422 healthy controls. Recombinant CD14 promoter
      luciferase reporter constructs, including the -159T or -159C allele, were
      transfected into K562 and BEAS-2B cells, and luciferase activities were measured
      and compared. Levels of serum sCD14 and interferon-gamma secreted by peripheral
      blood mononuclear cells (PBMCs) were measured using enzyme-linked immunosorbent
      assay.The frequency of -159TT genotypes was higher in tuberculosis patients than
      in healthy controls. The promoter activity of the -159T allele was higher than
      that of the -159C allele. Serum sCD14 levels were higher among tuberculosis
      patients with -159TT genotypes than among those with -159CC genotypes and
      interferon-gamma release by PBMCs was decreased in subjects with -159TT
      genotypes. In conclusion, the -159TT CD14 genotypes were associated with
      tuberculosis development in Koreans. This association might be a result of the
      higher promoter activity of the -159T allele, the higher level of sCD14, and the
      decreased interferon-gamma secretion in subjects with -159TT genotypes.

PMID- 19758337
TI  - Comparative in situ topoproteome analysis reveals differences in patch test
      induced eczema: cytotoxicity-dominated nickel versus pleiotrope pollen reaction.
AB  - A subgroup of patients with atopic eczema develops acute eczematous reactions to
      type I allergy-inducing agents such as pollen that clinically resemble type IV
      allergies induced by haptens like metal ions. To clarify the underlying
      immunologic mechanisms, this study was designed to map the inflammatory in situ
      topoproteome of eczematous responses to grass/birch pollen and nickel by using
      atopy patch test (APT) and nickel patch test (NPT) as an appropriate clinical
      model, respectively. Biopsies from NPT (n = 6) and APT (n = 6) with positive
      reactions at 72 h were analysed by multiple epitope ligand cartography (MELC),
      which enabled to investigate coexpression of 49 different epitopes
      immunohistochemically in a single given tissue section. Colocalisation of IgE and
      FcepsilonRI was investigated by confocal microscopy. Compared with APT responses,
      NPT reactions were dominated by cytotoxic TIA-1 + and CD8 + T cells. In contrast,
      the immune response in APT reactions appeared more pleiotrope - as detected by
      colocalisation analysis. Multiple combinatorial molecular phenotype (CMP) motifs
      containing naive, early maturation and memory T cell (CD45RA, CD7, CD44, CD45R0),
      and general activation markers (CLA, HLA-DR, CD13, CD29, CD58, CD71, CD138) were
      significantly higher expressed in APT when compared with NPT reactions. APT
      response was confirmed to be accompanied by IgE bound to FcepsilonRI. In summary,
      our results demonstrate that the NPT reaction is clearly dominated by cytotoxic
      events, while the APT reaction to pollen grains is more heterogeneous and elicits
      a combined humoral and cellular immune reaction.

PMID- 19758338
TI  - Fetuin-A promotes primary keratinocyte migration: independent of epidermal growth
      factor receptor signalling.
AB  - Previously, we reported that fetuin-A is a major component of ovine foetal skin
      and significantly enhances 'wound closure' in primary keratinocyte cultures. In
      this study, we found that in human newborn foreskin, a high level of fetuin-A
      protein is detected throughout the dermis. However, in adult skin a low level of
      fetuin-A is observed throughout the epidermal and dermal layers, except at
      regions surrounding hair follicles and at the epidermal-dermal junction where the
      level of fetuin-A is relatively high. Fetuin-A significantly induces actin-rich
      protrusions in human primary keratinocytes. Interestingly, blockade of epidermal
      growth factor (EGF) receptor signalling has a limited effect on fetuin-A promoted
      'wound closure' on primary human keratinocytes, but significantly inhibits fetuin
      A's effect on HaCaT cells. These results indicate that high levels of fetuin-A
      may partially contribute to less scar formation in newborn foreskin and that the
      effect of fetuin-A on primary keratinocyte migration is independent of EGF
      receptor signalling.

PMID- 19758339
TI  - Isolation of human eosinophils: microbead method has no impact on IL-5 sustained
      viability.
AB  - BACKGROUND/PURPOSE: In a recent issue of Experimental Dermatology (18, 2009,
      654), Schefzyk et al. concluded that multi-antibody eosinophil isolation
      (Miltenyi) should be abandoned, as differential purity was minimal, and
      eosinophils underwent accelerated apoptosis when compared with those isolated
      with traditional anti-CD16 microbeads. Our intent was to investigate the
      universality of these findings. METHODS: We isolated eosinophils from normal
      donor granulocyte packs using two methods, and evaluated purity, viability and
      annexin-V/propidium-iodide staining. RESULTS: Purity was substantially greater
      when multi-antibody isolation was used for eosinophil isolation from granulocyte
      packs (98% vs 69%). No differential survival was detected when eosinophils were
      maintained in culture with or without interleukin-5. CONCLUSIONS: Multi-antibody
      eosinophil isolation represents a substantial advantage over anti-CD-16
      microbeads when isolating large numbers of eosinophils from concentrated
      leucocyte preparations. No differential survival was observed. While appropriate
      consideration of methods is always crucial, multi-antibody eosinophil isolation
      should not be abandoned completely.

PMID- 19758340
TI  - The potential role of c-Jun activation in patients with cutaneous lichen planus.
AB  - c-Jun, a component of the activating protein-1 transcription factor family, has
      been known to play an important role in the control of cell proliferation. It is
      also suspected to be a critical mediator of tumor promotion. However,
      investigations of c-Jun activation patterns in inflammatory and inflammatory
      transforming skin diseases have not been described so far. In this work, we show
      the c-Jun activation pattern in skin samples of patients with cutaneous lichen
      planus (LP), squamous cell carcinoma (SCC), psoriasis and normal skin using an
      immunohistochemical approach and Western blot analysis. In addition, we studied
      the c-Jun activation pattern in histological samples of three patients in whom LP
      transformed to SCC. We show that c-Jun is rarely activated in normal skin and
      psoriasis in contrast to LP and SCC. Our results suggest that c-Jun activation in
      human skin is involved in (1) proliferation and (2) could potentially participate
      in the transformation of LP from an inflammatory to a carcinogenic state.
      Nevertheless, JNK1/2, an important c-Jun activating kinase, was not found to be
      differentially regulated in LP and SCC compared with normal skin.

PMID- 19758341
TI  - Enhanced T-cell activation by immature dendritic cells loaded with HSP70
      expressing heat-killed melanoma cells.
AB  - Vaccination protocols that utilize dendritic cells (DCs) to elicit therapeutic
      immunity against tumors are the subject of intense research. Given that the
      capacity of DCs to cross-present antigens is physiologically low, there is
      considerable interest to develop strategies that enhance that pathway. In order
      to best exploit the enhanced cross-presentation of antigens bound to heat shock
      protein 70 (HSP70), we analysed melanoma cell preparations for their HSP70
      expression. Western blotting revealed strong upregulation of HSP70 after heat
      killing in contrast to UV-B irradiation. When the uptake of heat-killed necrotic
      cells by DCs at various levels of maturation was assessed, 61 +/- 7% of immature
      DCs (iDCs) internalized fluorescence-labelled necrotic material. Apoptotic
      material from UV-B-irradiated cells was internalized by only 48 +/- 5% of iDCs.
      Maturation-inducing cytokines did not affect the uptake when added simultaneously
      with the tumor cell preparations. Loading DCs with heat-necrotic or apoptotic
      melanoma cells slightly reduced CD83 expression while leaving CD208 (DC-LAMP)
      expression unchanged. As determined by IFN-gamma-detecting enzyme-linked
      immunospot assays, iDCs loaded with heat-killed melanoma cells activated
      autologous T cells most effectively when used without any further maturation,
      whereas DCs loaded with apoptotic material required maturation. In conclusion,
      HSP70-expressing melanoma cells could be generated by heat-killing. Loading iDCs
      with heat-killed melanoma cells resulted in a superior priming of autologous T
      cells in vitro.

PMID- 19758342
TI  - Application of stereology to dermatological research.
AB  - Stereology is a set of mathematical and statistical tools to estimate three
      dimensional (3-D) characteristics of objects from regular two-dimensional (2-D)
      sections. In medicine and biology, it can be used to estimate features such as
      cell volume, cell membrane surface area, total length of blood vessels per volume
      tissue and total number of cells. The unbiased quantification of these 3-D
      features allows for a better understanding of morphology in vivo compared with 2
      D methods. This review provides an introduction to the field of stereology with
      specific emphasis on the application of stereology to dermatological research by
      supplying a short insight into the theoretical basis behind the technique and
      presenting previous dermatological studies in which stereology was an integral
      part. Both the theory supporting stereology and a practical approach in a
      dermatological setting are reviewed with the aim to provide the reader with the
      capability to better assess papers employing stereological estimators and to
      design stereological studies independently.

PMID- 19758343
TI  - Serum levels of IL-18 and sIL-2R in patients with alopecia areata receiving
      combined therapy with oral cyclosporine and steroids.
AB  - This study was to determine which immunologic factors contribute to the prognosis
      of patients with alopecia areata (AA) who were receiving oral cyclosporine A and
      methylprednisolone. Patients with > 25% hair regrowth were defined as responders,
      and patients exhibiting < or = 25% regrowth were poor-responders. The serum
      levels of IL-18 and soluble IL-2 receptor (sIL-2R) were measured at baseline in
      21 patients with AA and 22 control subjects. The mean serum level of IL-18 in the
      patients with extensive AA was significantly higher than that in the control
      subjects. The mean serum concentration of sIL-2R in the AA patients significantly
      decreased after 1 month of treatment. The mean basal serum level of IL-18 was
      highest in the responder, whereas the baseline level of sIL-2R was significantly
      higher in the poor-responder group than other groups. In conclusion, increased
      serum sIL-2R level and lower IL-18 level at baseline was associated with a poor
      prognosis in patients with AA.

PMID- 19758344
TI  - Haptoglobin binds the antiatherogenic protein apolipoprotein E - impairment of
      apolipoprotein E stimulation of both lecithin:cholesterol acyltransferase
      activity and cholesterol uptake by hepatocytes.
AB  - Haptoglobin (Hpt) binds apolipoprotein A-I (ApoA-I), and impairs its stimulation
      of lecithin:cholesterol acyltransferase (LCAT). LCAT plays a major role in
      reverse cholesterol transport (RCT). Apolipoprotein E (ApoE), like ApoA-I,
      promotes different steps of RCT, including LCAT stimulation. ApoE contains amino
      acid sequences that are homologous with the ApoA-I region bound by Hpt and are
      involved in the interaction with LCAT. Therefore, Hpt was expected to also bind
      ApoE, and inhibit the ApoE stimulatory effect on LCAT. Western blotting and ELISA
      experiments demonstrated that the Hpt beta-subunit binds ApoE. The affinity of
      Hpt for ApoE was higher than that for ApoA-I. High ratios of Hpt with either
      apolipoprotein, such as those associated with the acute phase of inflammation,
      inhibited, in vitro, the stimulatory effect of ApoE on the cholesterol
      esterification activity of LCAT. Hpt also impaired human hepatoblastoma-derived
      cell uptake of [(3)H]cholesterol from proteoliposomes containing ApoE or ApoA-I.
      We suggest that the interaction between Hpt and ApoE represents a mechanism by
      which inflammation affects atherosclerosis progression. Hpt might influence ApoE
      function in processes other than RCT.

PMID- 19758346
TI  - Environmental determinants correlated to Vibrio harveyi-mediated death of marine
      gastropods.
AB  - Vibrio harveyi is an emerging pathogen that causes mass mortality in a wide
      variety of marine animal species; however, it is still unclear which
      environmental determinants correlate V. harveyi dynamics and the bacterium
      mediated death of marine animal life. We conducted a correlation analysis over a
      5-year period (2003-2007) analysing the following data: V. harveyi abundance,
      marine animal mortality and environmental variables (seawater temperature,
      salinity, pH, chlorophyll a, rainfall and total viable bacterial counts). The
      samples were collected from a coastal area in northern Japan, where deaths of a
      marine gastropod species (Haliotis discus hannai) have been reported. Our
      analysis revealed significant positive correlations between average seawater
      temperature and average V. harveyi abundance (R = 0.955; P < 0.05), and between
      average seawater temperature and V. harveyi-mediated abalone death (R = 0.931; P
      < 0.05). Based on the regression model, n degrees C rise in seawater temperature
      gave rise to a 21(n)-fold increase in the risk of mortality caused by V. harveyi
      infection. This is the first report providing evidence of the strong positive
      correlation between seawater temperature and V. harveyi-mediated death of marine
      species.

PMID- 19758347
TI  - Detailed analysis of the microdiversity of Prochlorococcus populations along a
      north-south Atlantic ocean transect.
AB  - In order to understand how environmental factors shape the diversity of
      Prochlorococcus in the Atlantic Ocean, we have elucidated the microdiversity
      along a north-south transect. The polymerase chain reaction-restriction fragment
      length polymorphism analysis of the genetic diversity of rpoC1 gene fragments of
      Prochlorococcus at 12 sampling sites revealed a latitudinal pattern in
      Prochlorococcus RFLP-type diversity in the samples collected from two depths. At
      the depth to which 14% of surface irradiance penetrated, HLII clones dominated
      the stations closest to the equator. The percentage of HLI clones increased with
      distance from the equator and LL clones were found only at the most northern and
      southern stations. In contrast, deeper (1% light depth) water samples did not
      show any overall trend in Prochlorococcus diversity or clade dominance.
      Multivariate statistical analyses indicated that Prochlorococcus diversity was
      linked to water temperature (partially an effect of latitude) and depth (which
      was linked to light penetration and turbidity). Phylogenetic analysis of the
      sequences obtained from the 423 different environmental RFLP-types detected in
      this study indicated that the HLII and HLI populations were composed of a wide
      range of genetically different clones, while the LL Prochlorococcus clade was
      less diverse, although half of the samples screened in this study derived from
      the 1% light depth.

PMID- 19758348
TI  - Characterization and evolution of two bacteriome-inhabiting symbionts in cixiid
      planthoppers (Hemiptera: Fulgoromorpha: Pentastirini).
AB  - Like other plant sap-sucking insects, planthoppers within the family Cixiidae
      (Insecta: Hemiptera: Fulgoromorpha) host a diversified microbiota. We report the
      identification and first molecular characterization of symbiotic bacteria in
      cixiid planthoppers (tribe: Pentastirini). Using universal eubacterial primers we
      first screened the eubacterial 16S rRNA sequences in Pentastiridius leporinus
      (Linnaeus) with PCR amplification, cloning, and restriction fragment analysis. We
      identified three main 16S rRNA sequences that corresponded to a Wolbachia
      bacterium, a plant pathogenic bacterium, and a novel gammaproteobacterial
      symbiont. A fourth bacterial species affiliated with 'Candidatus Sulcia muelleri'
      was detected in PCR assays using primers specific for the Bacteroidetes. Within
      females of two selected cixiid planthoppers, P. leporinus and Oliarus filicicola,
      fluorescence In situ hybridization analysis and transmission electron microscopy
      observations showed that 'Ca. Sulcia muelleri' and the novel gammaproteobacterial
      symbiont were housed in separate bacteriomes. Phylogenetic analysis revealed that
      both of these symbionts occurred in at least four insect genera within the tribe
      Pentastirini. 'Candidatus Purcelliella pentastirinorum' was proposed as the novel
      gammaproteobacterial symbiont.

PMID- 19758349
TI  - Isolation and characterization of a novel Borrelia group of tick-borne borreliae
      from imported reptiles and their associated ticks.
AB  - The members of the genus Borrelia are transmitted by arthropods and known to be
      infectious to vertebrates. Here we found isolates and DNAs belonging to the
      Borrelia turcica and unknown Borrelia species from imported reptiles and their
      ectoparasites. The Borrelia strains were isolated from blood and multiple organs
      of exotic tortoises, and were experimentally infectious to captive-bred
      tortoises. These findings suggest that these tortoises may be a candidate as the
      reservoir host of the Borrelia species. In this study, the Borrelia strains were
      also isolated from and/or detected in hard-bodied ticks, Amblyomma ticks and
      Hyalomma ticks. In some of these ticks, immunofluorescence imaging analysis
      revealed that the Borrelia had also invaded into the tick salivary glands.
      Accordingly, these ticks were expected to be a potential vector of the Borrelia
      species. Sequencing analyses of both housekeeping genes (flaB gene, gyrB gene and
      16S rDNA gene) and 23S rRNA gene-16S rRNA gene intergenic spacer region revealed
      that these Borrelia strains formed a monophyletic group that was independent from
      two other Borrelia groups, Lyme disease Borrelia and relapsing fever Borrelia.
      From these results, the novel group of Borrelia comprises the third major group
      of arthropod-transmitted borreliae identified to date.

PMID- 19758350
TI  - Viral-mediated lysis of microbes and carbon release in the sub-Antarctic and
      Polar Frontal zones of the Australian Southern Ocean.
AB  - Viral production was determined in the sub-Antarctic zone (SAZ) to the southwest
      and southeast of Tasmania and in the Polar Frontal zone (PFZ) of the Australian
      sector of the Southern Ocean during Austral summer (January-February 2007).
      Concentrations of viruses were the lowest (6.6 x 10(9) particles l(-1)) in the
      PFZ and the highest (2.1 x 10(10) particles l(-1)) in the eastern SAZ where
      nutrient input from the East Australian Current (EAC) sustained higher
      concentrations of bacteria and bacterial production relative to the west. Rates
      of viral production in the PFZ (1.8 x 10(10) viruses l(-1) day(-1)) were lower
      than those in the western SAZ (2.5 x 10(10) viruses l(-1) day(-1)). Viral
      production in the eastern SAZ (2.2 x 10(11) viruses l(-1) day(-1)) was the
      highest recorded and was approximately one order of magnitude higher than at the
      other sites. In the western SAZ and PFZ, the percentage of available bacterial
      biomass lysed by viruses was similar (23.5% and 23% respectively) equating to the
      release of 3.3 and 2.3 microg carbon l(-1) day(-1) respectively (assuming a burst
      size of 50 viruses host(-1)). In the eastern SAZ the potential bacterial biomass
      lysed was higher (on average 40%) and corresponded to the release of 26.5 microg
      carbon l(-1) day(-1). These findings suggest the importance of the viral shunt in
      carbon cycling within these regions.

PMID- 19758351
TI  - Optimization of isolation and further characterization of umbilical-cord-blood
      derived very small embryonic/ epiblast-like stem cells (VSELs).
AB  - Because of their small size and density, umbilical cord blood (UCB)-derived very
      small embryonic/epiblast-like stem cells (VSELs) are usually lost at various
      steps of UCB preparation. Accordingly, we noticed that a significant number of
      these cells, which are smaller than erythrocytes, are lost during gradient
      centrifugation over Ficoll-Paque as well as during routine volume depletion of
      UCB units before freezing. To preserve these cells in final UCB preparations, we
      propose a relatively short and economical three-step isolation protocol that
      allows recovery of approximately 60% of the initial number of Lin(-)/CD45(
      )/CD133(+) UCB-VSELs present in freshly harvested UCB units. In this novel
      approach (i) UCB is lysed in a hypotonic ammonium chloride solution to deplete
      erythrocytes; (ii) CD133(+) including VSELs cells are enriched by employing
      immunomagnetic beads; and subsequently (iii) Lin(-)/CD45(-)/CD133(+) cells are
      sorted by fluorescence-activated cell sorting. The whole isolation procedure
      takes approximately 2-3 h per UCB unit and isolated cells are highly enriched for
      an Oct-4(+) and SSEA-4(+) population of small Lin(-)/CD45(-)/CD133(+) cells.

PMID- 19758352
TI  - Observer variation in the echocardiographic measurement of maximum atrial septal
      excursion: a comparison of M-mode with two-dimensional or transesophageal
      echocardiography.
AB  - BACKGROUND: Atrial septal aneurysm is typically diagnosed by transthoracic two
      dimensional or transesophageal echocardiography (2DE or TEE). Such techniques are
      highly dependent on visual inspection which predisposes to observer variation.
      This study compares inter- and intraobserver variations in the measurement of
      maximum atrial septal excursion (MASE) obtained using transthoracic M-mode
      echocardiography (MME) with that obtained using 2DE or TEE. METHODS: Consecutive
      patients with highly mobile atrial septal motion by visual inspection during 2DE
      or TEE were studied. MASE was estimated visually on 2DE or TEE. MME tracings were
      obtained with the cursor bisecting the parabola formed by the atrial septum at
      its maximum deviation from the midline. Electronic calipers were used to measure
      MASE for all echocardiographic techniques. Two observers provided two
      measurements each. Observer variation was determined by assessing standard
      deviation and confidence intervals of inter- and intraobserver differences.
      RESULTS: Interobserver analysis showed standard deviations of 0.077 cm (95% CI
      0.065-0.094) for MME and 0.280 cm (95% CI 0.242-0.334) for 2DE or TEE.
      Intraobserver analysis showed standard deviations of 0.08 cm (95% CI 0.068-0.101)
      for MME and 0.318 cm (95% CI 0.274-0.381) for 2DE or TEE. The mean magnitude of
      measured MASE was 0.44 cm higher with MME than with 2DE or TEE (95% CI 0.068
      0.101). CONCLUSIONS: MME assessment of MASE is associated with substantially
      lower inter- and intraobserver variation than 2DE or TEE assessment. The
      magnitude of MASE is substantially higher with MME than with 2DE or TEE.

PMID- 19758353
TI  - Mohs surgery for basal cell carcinoma assisted by dermoscopy: report of two
      cases.

PMID- 19758354
TI  - Case series of multiple recurrent reactive keratoacanthomas developing at
      surgical margins.

PMID- 19758355
TI  - Ulcerated malignant spindle-cell neoplasm of the finger: malignant peripheral
      nerve sheath tumor or desmoplastic malignant melanoma?

PMID- 19758356
TI  - Analysis of glycaemic control and weight change in patients initiated with human
      or analog insulin in an US ambulatory care setting.
AB  - BACKGROUND: Insulin is a mainstay in the treatment of type 1 diabetes and is a
      recommended option in patients with type 2 diabetes who fail to maintain
      glycaemic control on other non-insulin therapies. The purpose of this study was
      to describe patient characteristics and evaluate changes in glycaemic control and
      weight in patients treated with insulin in an ambulatory care setting. METHODS:
      Patients with diabetes were identified from the General Electric electronic
      medical record (EMR) database (1 September 2004 to 30 April 2008). Patients were
      > or =18 years, insulin naive, newly treated with monoinsulin therapy (index
      date). Baseline characteristics were identified overall and stratified by insulin
      type (basal, mixed, and rapid). Basal insulins were described by human versus
      analog and for insulin detemir and insulin glargine. Change in haemoglobin A1C
      (HbA1C) and weight from baseline (45 days pre- to 15 days postindex date) to 6
      months (+/-90 days) were compared. Regression analyses were used to evaluate
      HbA1C outcomes across insulins and for the likelihood of gaining 0.9 kg (2 lbs)
      for detemir versus glargine controlling for baseline characteristics. RESULTS: A
      total of 12 136 patients were included. A majority were initiated on a basal
      insulin (64.7%) followed by mixed (20.8%) and rapid (14.4%). Basal users had
      significantly higher mean body weight and lower mean baseline HbA1C than mixed
      users (p < 0.001 for all), and were significantly older, had higher baseline
      HbA1C and higher baseline body mass index (BMI) than rapid insulin users (p <
      0.001 for all). Glargine patients had a significantly higher mean baseline HbA1C
      (p = 0.003) than detemir patients. The adjusted reduction in HbA1C was greater
      for rapid insulin than for mixed or basal insulin (p < or = 0.05). The adjusted
      differences in HbA1C between basal human and basal analog insulins and between
      detemir and glargine were not statistically significant (p > 0.05). Patients
      using detemir were 30% less likely to gain 0.9 kg or more than glargine users (p
      < 0.05). CONCLUSIONS: HbA1C outcomes in the ambulatory care setting were
      generally not different between insulin classes. The likelihood of weight gain
      was less with insulin detemir than with insulin glargine. Thus, real-world weight
      outcomes for basal analog insulin may differ by specific product.

PMID- 19758357
TI  - The European Exenatide study of long-term exenatide vs. glimepiride for type 2
      diabetes: rationale and patient characteristics.
AB  - AIM: To describe the rationale for the European Exenatide (EUREXA) clinical study
      and describe the characteristics of the patient cohort. METHODS: EUREXA is a
      multinational study of long-term effects of add-on exenatide vs. glimepiride in
      patients with type 2 diabetes and failure of diet/lifestyle plus metformin
      monotherapy. Metformin failure was defined as hemoglobin A1c (HbA1c) > or = 6.5%
      and patients were overweight/obese (BMI > or = 25 to < 40 kg/m(2)). The primary
      end point is time to failure of combination treatment, defined from HbA1c
      concentration according to current criteria. At baseline, an oral glucose
      tolerance test (OGTT) was performed, fasting blood was taken for lipid profile
      and patients were randomized to add-on exenatide (5 microg b.i.d. for 4 weeks
      then 10 microg b.i.d.) or glimepiride (1 mg/day titrated to maximum dose).
      RESULTS: A total of 1039 patients were entered in the study, with mean (+/- s.d.)
      age 57.2 +/- 9.6 years, body mass index (BMI) 32.4 +/- 4.1 kg/m(2), duration of
      diabetes 5.6 +/- 4.5 years and HbA1c 7.4 +/- 0.7%. A history of cardiovascular
      disease (CVD) was present for 64.8% of patients overall and duration of diabetes
      was statistically significantly longer for patients with CVD than without (p =
      0.010). Lipid abnormalities were reported for 48.9% of patients and 40.9% were
      taking at least one lipid-lowering medication. CONCLUSION: Patients included in
      the EUREXA study had early failure of glucose control with metformin and
      presented typical features of type 2 diabetes: overweight/obesity and high
      prevalence of lipid abnormalities and CVD. In this population, the effects of
      exenatide vs. glimepiride will be evaluated over at least 2.5 years.

PMID- 19758358
TI  - Weight and blood pressure response to weight management and sibutramine in
      diabetic and non-diabetic high-risk patients: an analysis from the 6-week lead-in
      period of the sibutramine cardiovascular outcomes (SCOUT) trial.
AB  - OBJECTIVE: To assess treatment responses to sibutramine and weight management in
      diabetic patients during the lead-in period of the Sibutramine Cardiovascular
      OUTcomes (SCOUT) trial. METHODS: SCOUT is an ongoing, prospective, randomized,
      double-blind, placebo-controlled outcome trial in cardiovascular high-risk
      overweight/obese patients. A total of 10 742 patients received single-blind
      sibutramine and individualized weight management during the 6-week lead-in
      period; 84% had a history of type 2 diabetes mellitus and additional co
      morbidities. Post-hoc analyses assessed anthropomorphic and vital sign responses
      between patients with and without diabetes. RESULTS: Concomitant antidiabetic
      medication use was reported by 86% of the diabetic patients (approximately 30%
      required insulin-alone or in combination). Body weight and waist circumference
      decreased in diabetic patients: median 2.1 kg; 2.0 cm (both men and women); for
      those on insulin: 1.9 kg; 1.5/2.0 cm (men/women); without insulin: 2.3 kg; 2.0 cm
      (both men and women); blood pressure (BP) was also reduced (median
      systolic/diastolic 3.5/1.0 mmHg) with larger reductions in diabetic patients who
      were hypertensive and/or lost the most weight (>5%). In diabetic patients who
      entered with BP at target (<130/<85 mmHg) but did not lose weight (N = 245),
      increases of 3.5/2.0 mmHg were observed. Non-diabetic patients had greater weight
      losses (2.5 kg) but smaller reductions in BP (systolic/diastolic -2.5/-0.5 mmHg).
      Pulse rate increases were less in diabetic vs. non-diabetic patients (1.5 vs. 2.0
      bpm). CONCLUSION: In these high-risk diabetic patients, sibutramine and lifestyle
      modifications for 6 weeks resulted in small, but clinically relevant, median
      reductions in body weight, waist circumference and BP. A small median increase in
      pulse rate was recorded.

PMID- 19758359
TI  - Alogliptin added to insulin therapy in patients with type 2 diabetes reduces
      HbA(1C) without causing weight gain or increased hypoglycaemia.
AB  - AIMS: To assess the efficacy and safety of alogliptin added to insulin in
      patients with type 2 diabetes inadequately controlled with insulin alone or
      combined with metformin. METHODS: In this 26-week, double-blind, placebo
      controlled study, 390 patients were randomized to receive alogliptin 12.5 mg (n =
      131), alogliptin 25 mg (n = 129) or placebo (n = 130) once daily, as add-on to
      stable insulin therapy with or without metformin. The primary endpoint was change
      in haemoglobin A(1C) (HbA(1C)) at week 26. RESULTS: At week 26, mean HbA(1C)
      changes from the mean baseline value of 9.3% were significantly greater for
      alogliptin 12.5 mg (-0.63 +/- 0.08%) and alogliptin 25 mg (-0.71 +/- 0.08%) than
      placebo (-0.13 +/- 0.08%; p < 0.001). Significantly greater proportions of
      patients receiving alogliptin 12.5 or 25 mg than placebo had HbA(1C) decreases of
      > or =0.5, > or =1.0 and > or =1.5%. Insulin doses remained unchanged, and there
      were no differences in the proportions of patients experiencing hypoglycaemia
      among placebo (24%), alogliptin 12.5 mg (27%) and alogliptin 25 mg (27%). Mean
      weight increases from baseline at week 26 were similar for placebo (0.6 +/- 0.2
      kg), alogliptin 12.5 mg (0.7 +/- 0.2 kg) and alogliptin 25 mg (0.6 +/- 0.2 kg).
      Incidences of overall adverse events, and of gastrointestinal, dermatological and
      infection-related events, were similar among groups. CONCLUSIONS: Adding
      alogliptin to previous insulin therapy (with or without metformin) significantly
      improved glycaemic control in patients with type 2 diabetes inadequately
      controlled on insulin, without causing weight gain or increasing the incidence of
      hypoglycaemia. Further studies are warranted to explore the role of alogliptin
      added to optimized basal insulin regimens.

PMID- 19758360
TI  - Patient-reported outcomes in a survey of patients treated with oral
      antihyperglycaemic medications: associations with hypoglycaemia and weight gain.
AB  - AIM: To examine the association between medication side-effects (SEs) and patient
      reported outcomes (PROs) among patients with type 2 diabetes treated with oral
      antihyperglycaemic agents (OAHAs). METHODS: A total of 1984 participants
      responded to an internet-based survey in the United States. Data were collected
      on hypoglycaemia 6 months and weight gain 12 months prior to the survey. Health
      related quality of life (HRQoL) was measured using the EuroQol-5D (EQ-5D). Also
      administered were the Treatment Satisfaction Questionnaire for Medication v.1.4
      (TSQM) and the Hypoglycaemia Fear Survey II (HFS). RESULTS: Symptoms of
      hypoglycaemia were reported by 62.9% of participants, and 36.9% reported weight
      gain. For those reporting hypoglycaemia, mean scores were lower for TSQM and EQ
      5D and higher for HFS when compared with those with no symptoms (TSQM: 69.7 vs.
      75.1; EQ-5D: 0.78 vs. 0.86; HFS: 17.5 vs. 6.2; all p < 0.0001). The same remained
      true when accounting for symptom severity, where severity was monotonically
      related with PRO scores (all p < 0.0001). Similarly, reported weight gain was
      associated with lower treatment satisfaction (69.0 vs. 73.3) and HRQoL (0.77 vs.
      0.83), and increased fear of hypoglycaemia (15.7 vs. 11.8) (all p < 0.0001). In
      mixed linear regression analysis, the associations between medication SEs and
      PROs remained significant after adjusting for patient and disease
      characteristics. CONCLUSIONS: Among patients with type 2 diabetes treated with
      OAHAs, self-reported hypoglycaemia and weight gain were associated with decreased
      treatment satisfaction and HRQoL. In addition, the presence of these SEs was
      associated with increased fear of hypoglycaemia.

PMID- 19758361
TI  - Sterol regulatory element-binding protein-1c knockdown protected INS-1E cells
      from lipotoxicity.
AB  - OBJECTIVE: The reduction in insulin secretory capacity and beta-cell mass has
      been attributed, at least partially, to lipotoxicity, which may contribute to the
      development of type 2 diabetes. Chronic free fatty acids (FFA) exposure impairs
      pancreatic beta-cell function and induces beta-cell apoptosis. This study is to
      elucidate the underlying molecular mechanisms. RESEARCH DESIGN AND METHODS: We
      exposed INS-1E pancreatic beta-cell line to palmitate or oleate, and measured the
      glucose stimulated insulin secretion (GSIS). The effect of FFA on sterol
      regulatory element-binding protein (SREBP)-1c lipogenic pathway, and expression
      of genes involved in beta-cell functions, including AMPK (AMP-activated protein
      kinase), UCP-2 (uncoupling protein-2), IRS-2 (insulin receptor substrate-2), PDX
      1 (pancreatic duodenal homeobox-1), GLUT-2 (glucose transporter-2) and B cell
      lymphoma/leukaemia-2 (Bcl-2) were investigated. Apoptosis of these exposed cells
      was determined by MitoCapture, Annexin V-Cy3 or terminal deoxynucleotidyl
      transferase-mediated dUTP nick-end labeling assay. Cell lipid accumulation was
      measured by oil red O staining or TG extraction. Also SREBP-1c expression
      knockdown were used. RESULTS: FFA treatment resulted in SREBP-1c overexpression,
      impaired GSIS, lipid accumulation, apoptosis of INS-1E cells. In addition, the
      expression of lipogenic genes and UCP-2 were upregulated, but AMPK, IRS-2, PDX-1,
      GLUT-2 and Bcl-2 were downregulated in the exposed cells. However, these
      lipotoxic effects of FFA were largely prevented by induction of a SREBP-1c small
      interfering RNA. CONCLUSIONS: These data suggest a strong correlation between FFA
      treatment and SREBP-1c activation in INS-1E cells. SREBP-1c might be a major
      factor responsible for beta-cell lipotoxicity, and SREBP-1c knockdown could
      protect INS-1E cells from lipotoxicity, which is implicating a therapeutic
      potential for treating diabetes related to lipotoxicity.

PMID- 19758362
TI  - Cessation of sporadic hemiplegic migraine attacks after patent foramen ovale
      closure.

PMID- 19758363
TI  - Socio-economic achievements of individuals born very preterm at the age of 27 to
      29 years.

PMID- 19758364
TI  - Intensive speech and language therapy for older children with cerebral palsy: a
      systems approach.
AB  - AIM: To investigate whether speech therapy using a speech systems approach to
      controlling breath support, phonation, and speech rate can increase the speech
      intelligibility of children with dysarthria and cerebral palsy (CP). METHOD:
      Sixteen children with dysarthria and CP participated in a modified time series
      design. Group characteristics were as follows: seven males, nine females; age
      range 12 to 18 years (mean 14y, SD 2); CP type: nine spastic, two dyskinetic,
      four mixed, one Worster-Drought; Gross Motor Function Classification System
      levels range I to V (median IV). Children received three 30- to 45-minute
      sessions of individual therapy per week for 6 weeks. Intelligibility in single
      words and connected speech was compared across four points: 1 week and 6 weeks
      before therapy, and 1 week and 6 weeks after its completion. Three familiar
      listeners and three unfamiliar listeners scored each recording. Mean percentage
      intelligibility was compared using general linear modelling techniques. RESULTS:
      After treatment, familiar listeners understood 14.7% more single words and 12.1%
      more words in connected speech. Unfamiliar listeners understood 15% more single
      words and 15.9% more words in connected speech after therapy. INTERPRETATION:
      Therapy was associated with increases in speech intelligibility. Effects of the
      therapy should be investigated further, in an exploratory trial with younger
      children and in a randomized controlled trial.

PMID- 19758365
TI  - Are the cognitive functions of children with Down syndrome related to their
      participation?
AB  - AIM: There is a lack of investigation into the functional developmental profile
      of children with Down syndrome. On the basis of current international health
      paradigms, the purpose of this study was to assess the developmental profile of
      these children. METHOD: Sixty children (33 males, 27 females) with Down syndrome
      (age range 6-16y; mean age 9y 3mo, SD 28.8mo), who had received standard,
      holistic, early intervention, were assessed. Of these, 42 (70%) had congenital
      anomalies, 12 had severe congenital heart defects. Participants were assessed on
      measures of cognitive function (Beery-Buktenica Developmental Test of Visual
      Motor Integration; Stanford-Binet Intelligence Scale) and participation (Vineland
      Adaptive Behaviour Scales). RESULTS: No difference was found on any measure on
      the basis of severity of congenital anomaly. Results showed improvements in age
      related body function and correlations between specific body functions and
      participation. No decline in IQ was found with age, and significant correlations
      between IQ and all other measures were noted. Although sex differences were found
      in the body functions of short-term memory and motor function, no difference in
      measures of activity performance and participation was found. INTERPRETATION: Our
      findings emphasize the need for paediatric Down syndrome intervention to
      encourage improved body functions while emphasizing the acquisition of functional
      skills that enable enhanced participation in age-appropriate activities.

PMID- 19758366
TI  - Early head growth: relation with IQ at 8 years and determinants in term infants
      of low and appropriate birthweight.
AB  - AIM: To investigate the relation between head growth at different periods and IQ
      at 8 years, and to identify factors associated with more rapid head growth.
      METHOD: Two parallel cohorts of term low birthweight (LBW) and appropriate
      birthweight (ABW) infants were enrolled at birth in northeast Brazil.
      Anthropometric measurements were made at birth, 2 months, 6 months, 12 months, 24
      months, and 8 years. Cognition was assessed at 8 years (n=164) with the Wechsler
      Intelligence Scale for Children. Multivariable analysis with a two-stage residual
      model was used to relate head growth between successive time points with IQ.
      RESULTS: Mean birthweight was 2.35kg (SD 0.15) in the LBW group (33 males, 50
      females), and 3.21kg (SD 0.15) in the ABW group (28 males, 53 females). Mean
      gestational age was 38.8 weeks (SD 1.4) and 40.0 weeks (SD 1.3) respectively. In
      the LBW group, head growth from birth to 2 months and from 2 to 6 months,
      conditional on previous size, were significant independent predictors of IQ at 8
      years. Conditional head growth from 6 months to 8 years and head size at birth
      were unrelated to IQ. In the ABW group there was no significant relation between
      conditional head growth and IQ for any period. Determinants of more rapid head
      growth from birth to 6 months in LBW infants were maternal height and rate of
      infant weight gain. INTERPRETATION: Head growth from birth to 6 months in term
      LBW infants is more important than prenatal or later postnatal head growth in
      predicting IQ at 8 years.

PMID- 19758367
TI  - Umbilical cord blood processing using Prepacyte-CB increases haematopoietic
      progenitor cell availability over conventional Hetastarch separation.
AB  - BACKGROUND: Currently the most frequently used method for umbilical cord blood
      separation in many hospitals across the UK and the rest of the world, where small
      to-medium amounts of samples are processed, is Hetastarch, a mechanical, starch
      based method, which causes red cell agglutination by rouleaux formation. AIM: In
      this study, a novel method (Prepa-Cyte-CB), in comparison with Hetastarch as part
      of an FDA-approved clinical study, was evaluated. MATERIALS AND METHODS:
      Validation of data included recovery of nucleated and CD34+ cells, red blood cell
      reduction, colony forming unit potential, flow cytometric analysis and sterility
      tests. RESULTS: PrepaCyte-CB, in comparison with Hetastarch offers fast, reliable
      separation with improved recovery of nucleated cells, 72.03% (+/-8.48 SD)
      compared to 58.09% (+/-20.06 SD), and CD34+ haematopoietic progenitor cells, 76%
      (+/-19.54 SD) compared to 64.19% (+/-29.77 SD). PrepaCyte-CB was also 12-fold
      more efficient in removing red blood cells and haemoglobin (P < 0.001) than
      Hetastarch. CONCLUSIONS: These results show that PrepaCyte-CB offers superior
      separation of UCB when compared to Hetastarch.

PMID- 19758368
TI  - Influenza virus vaccination in kidney transplant recipients: serum antibody
      response to different immunosuppressive drugs.
AB  - INTRODUCTION: This study prospectively accessed the immune response to the
      inactivated influenza vaccine in renal transplant recipients receiving either
      azathioprine or mycophenolate mofetil (MMF). Side effects were investigated.
      METHODS: Sixty-nine patients received one dose of inactivated trivalent influenza
      vaccine. Antihemagglutinin (HI) antibody response against each strain was
      measured before and one to six months after vaccination. RESULTS: Geometric mean
      HI antibody titers for H1N1 and H3N2 strains increased from 2.57 and 2.44 to
      13.45 (p = 0.001) and 7.20 (p < 0.001), respectively. Pre- and post-vaccination
      protection rates for H1N1 and H3N2 increased from 8.7% to 49.3% (p < 0.001); and
      36.3% (p < 0.001) and seroconversion rates were 36% and 25.3%, respectively.
      There was no response to influenza B. The use of MMF reduced the H1N1 and H3N2
      protection rates and the seroconversion rate for the H1N1 strain when compared
      with the use of azathioprine, and subjects transplanted less than 87 months also
      had inferior antibody response. Adverse events were mild and there were no change
      on renal function post-vaccination. CONCLUSION: Renal transplant patients
      vaccinated against influenza responded with antibody production for influenza A
      virus strains, but not for influenza B. Use of MMF and shorter time from
      transplantation decreased the immune response to the vaccine.

PMID- 19758369
TI  - Successful treatment of hereditary angioedema with bradykinin B2-receptor
      antagonist icatibant.
AB  - The bradykinin B2 receptor antagonist icatibant has recently become available for
      treating hereditary angioedema. Our observations demonstrate icatibant to be
      effective and safe for the treatment of both, abdominal and cutaneous attacks in
      a practice setting beyond clinical studies.

PMID- 19758370
TI  - De novo intraepidermal epithelioid melanocytic dysplasia: a review of 263 cases.
AB  - BACKGROUND: De novo intraepidermal epithelioid melanocytic dysplasia (DNIEMD) is
      a newly characterized lesion that is associated with a personal and/or family
      history of malignant melanoma (MM) and/or dysplastic nevi (DN). However, the
      biological significance is still uncertain and the persons predisposed to this
      lesion have not been adequately described. METHODS: Clinicopathologic data of 258
      patients, from 263 biopsies diagnosed with DNIEMD, was obtained. A brief
      voluntary questionnaire was used to obtain demographic, risk factor and disease
      history. RESULTS: There is an 82% (n=263) predominance of women with DNIEMDs. For
      men and women, the distributions of these lesions occur on the lower extremities
      (71%), the upper extremities (24%) and trunk (5%). Thirty-one percent of the 258
      patients responded to the questionnaires. 48% of the 60 respondents had green or
      blue eyes. 26% of 62 respondents had a history of non-melanoma skin cancer
      (NMSC). Combined data revealed that 68% of 134 patients had a history of DN. As
      well, 24% of 89 patients had personal histories of melanoma, while 24% of 72
      patients had a family history of melanoma. CONCLUSION: Most of these DNIEMD
      lesions are found on the lower extremities of women and men, and they have an
      increased association with MM, DN and NMSC.

PMID- 19758371
TI  - Syringocystadenocarcinoma papilliferum in a linear nevus verrucosus.
AB  - Syringocystadenocarcinoma papilliferum (SCACP), the malignant counterpart of
      syringocystadenoma papilliferum (SCAP), is a rare form of adenocarcinoma of the
      skin. Only 11 well-documented case reports of SCACP have been published so far.
      An 83-year-old woman with a linear nevus verrucosus (LNV) on her right arm had a
      history of a nodule arising within this nevus that was diagnosed as SCAP by skin
      biopsy 7 years earlier. Since then, the nodule had enlarged gradually and formed
      an exophytic tumor with a moist surface, measuring 3 * 2.5 cm. The tumor was
      excised and studied by histologic examination. Although histologically the
      overall architecture of the tumor still resembled SCAP, transition to SCACP was
      obvious by the presence of areas of cytonuclear atypia, increased proliferative
      activity and infiltrative growth. The edges of the excised ellipse flanking the
      tumor showed typical microscopic features of LNV, but no organoid components of
      nevus sebaceus (NS).We report the 12th case of SCACP, the first case of SCACP on
      the arm and the first case of SCACP arising from pre-existing SCAP, in what
      appeared to be an epidermal nevus.

PMID- 19758372
TI  - Severe asthma: a consequence of over exuberant repair?

PMID- 19758373
TI  - Reduced helminth burden increases allergen skin sensitization but not clinical
      allergy: a randomized, double-blind, placebo-controlled trial in Vietnam.
AB  - BACKGROUND: Observational evidence suggests that infection with helminths
      protects against allergic disease and allergen skin sensitization. It is
      postulated that such effects are mediated by helminth-induced cytokine responses,
      in particular IL-10. OBJECTIVE: We tested this hypothesis in a rural area of
      central Vietnam where hookworm infection is endemic. METHODS: One thousand five
      hundred and sixty-six schoolchildren aged 6-17 were randomly allocated to receive
      either anti-helminthic therapy or a placebo at 0, 3, 6, and 9 months. We compared
      changes in the prevalence of exercise-induced bronchoconstriction, allergen skin
      sensitization, flexural eczema on skin examination, questionnaire-reported
      allergic disease (wheeze and rhinitis symptoms), and immunological parameters
      (hookworm-induced IFN-gamma, IL-5, IL-10) between 0 and 12 months. RESULTS: One
      thousand four hundred and eighty-seven children (95% of these randomized)
      completed the study. The most common helminth infections were hookworm (65%) and
      Ascaris lumbricoides (7%). There was no effect of the therapy on the primary
      outcome, exercise-induced bronchoconstriction (within-participant mean percent
      fall in peak flow from baseline after anti-helminthic treatment 2.25 (SD 7.3) vs.
      placebo 2.19 (SD 7.8, P=0.9), or on the prevalence of questionnaire-reported
      wheeze [adjusted odds ratio (OR)=1.16, 95% confidence interval (CI) 0.35-3.82,
      P=0.8] and rhinitis (adjusted OR=1.39, 0.89-2.15, P=0.1), or flexural dermatitis
      on skin examination (adjusted OR=1.15, 0.39-3.45, P=0.8). However, anti
      helminthic therapy was associated with a significantly higher allergen skin
      sensitization risk (adjusted OR=1.31, 1.02-1.67, P=0.03). This effect was
      particularly strong for children infected with A. lumbricoides at baseline
      (adjusted OR=4.90, 1.48-16.19, P=0.009). Allergen skin sensitization was
      inversely related to hookworm-specific IL-10 at baseline (adjusted OR=0.76, 0.59
      0.99, P=0.04). No cytokine tested, including IL-10, changed significantly after
      the anti-helminthic therapy compared with the placebo. CONCLUSION: A significant
      reduction in worm burden over a 12-month period in helminth-infected children
      increases the risk of allergen skin sensitization but not of clinical allergic
      disease. The effect on skin sensitization could not be fully explained by any of
      the immunological parameters tested.

PMID- 19758375
TI  - Plasmodium falciparum infection of the placenta impacts on the T helper type 1
      (Th1)/Th2 balance of neonatal T cells through CD4(+)CD25(+) forkhead box P3(+)
      regulatory T cells and interleukin-10.
AB  - Placental malaria infection affects the T helper type 1 (Th1)/Th2 balance in
      neonatal children. We investigated a potential role of regulatory T cells in this
      balance by comparing T cell responses of cord blood mononuclear cells (CBMC) from
      parasitized and non-parasitized placenta of Gambian women. CBMC were depleted of
      CD4(+)CD25(+) forkhead box P3 (FoxP3)(+) regulatory T cells and analysed in vitro
      for their ability to produce interferon (IFN)-gamma, sCD30 and interleukin (IL)
      10 in response to phytohaemagglutinin (PHA), live Plasmodium falciparum, schizont
      extracts and the recombinant P. falciparum blood stage antigen merozoite surface
      protein 1 (MSP1(19)). As expected, lower IFN-gamma and higher sCD30 responses
      were observed for the cells from the parasitized group. In addition, higher IL-10
      levels were produced by CBMC from the parasitized group. Depletion of regulatory
      T cells decreased IL-10 production, which resulted in a restoration of IFN-gamma
      expression in response to all stimuli. The Th2 marker sCD30 remained
      significantly higher in the parasitized group in response to malaria protein
      antigens while similar levels were recovered between both groups in response to
      live P. falciparum. Similar effects were observed by adding an antibody that
      blocks IL-10 function. These results suggest that the impact of P. falciparum
      infection on Th1 differentiation of neonatal T cells can be ascribed to
      regulatory T cells through production of IL-10.

PMID- 19758376
TI  - Novel and recurrent mutations in the AIRE gene of autoimmune polyendocrinopathy
      syndrome type 1 (APS1) patients.
AB  - Autoimmune polyendocrinopathy syndrome type 1 (APS1) is characterized by the
      presence of at least two out of three clinical features, which include Addison's
      disease, hypoparathyroidism, and chronic mucocutaneous candidiasis. This disorder
      is caused by mutations in the AIRE (autoimmune regulator) gene. While several
      AIRE mutations have been described in APS1 patients of various ethnic origins,
      the genetic cause of APS1 in Arab patients requires further investigation. This
      study describes seven Arab families, in which 18 patients had APS1. In addition
      to the cardinal features of APS1, some patients exhibited alopecia, diabetes
      mellitus, nephrocalcinosis and other phenotypes associated with APS1. DNA
      sequencing of the AIRE gene of patients from this study identified four novel and
      one recurrent mutation. These mutations likely result in loss of AIRE function in
      the patients. In addition, it was noted that the non-pathogenic c.834C> G
      mutation (rs1800520, encoding for p.Ser278Arg) occurs with high incidence in the
      AIRE gene of Arab individuals. Furthermore, this investigation demonstrates
      inflammation of the hair follicles in APS1 patients with alopecia universalis. We
      conclude that Arab APS1 patients carry novel and recurrent mutations in the AIRE
      gene.

PMID- 19758374
TI  - The role of T helper type 17 cells in inflammatory arthritis.
AB  - While T cells have been implicated in the pathogenesis of inflammatory arthritis
      for more than three decades, the focus on the T helper type 17 (Th17) subset of
      CD4 T cells and their secreted cytokines, such as interleukin (IL)-17, is much
      more recent. Proinflammatory actions of IL-17 were first identified in the 1990s,
      but the delineation of a distinct Th17 subset in late 2005 has sparked great
      interest in the role of these cells in a broad range of immune-mediated diseases.
      This review summarizes current understanding of the role of Th17 cells and their
      products in both animal models of inflammatory arthritis and human immune-driven
      arthritides.

PMID- 19758377
TI  - Dermatological signs in South Asian women induced by sari and petticoat
      drawstrings.
AB  - The sari, the elegant garment worn by Indian and many South Asian women, is
      associated with many cutaneous signs. With millions of South Asians settled all
      over the world, it is important for clinicians to be aware of the cutaneous
      associations of wearing a sari that is tied tightly around the waist with a
      drawstring. Lichenified linear hyperpigmented grooves, vitiligo, postinflammatory
      depigmentation, lichen planus and superficial cutaneous infections are some of
      the conditions seen in women wearing this garment. This review is one of the very
      few detailed reports of this widely worn garment and its dermatological
      associations.

PMID- 19758379
TI  - A case of Mycobacterium abscessus skin infection caused by multiple acupunctures.

PMID- 19758380
TI  - Recipient site preparation for epidermal grafting using carbon dioxide Silktouch
      laser.

PMID- 19758381
TI  - Physiological skin conditions of preterm and term neonates.
AB  - Skin problems in children during the first few weeks of life can raise concern,
      even for experienced neonatologists and paediatric dermatologists. The skin of
      preterm and term newborn babies has distinct differences from juvenile and adult
      skin. An understanding of the nature of neonatal skin, the physiological and
      nonphysiological skin conditions of preterm and term neonates, and skin care are
      essential in paediatric practice. This article discusses the nature of the
      neonatal skin and its physiological phenomena.

PMID- 19758382
TI  - An unusual presentation of lichen sclerosus et atrophicus in a tattoo.

PMID- 19758383
TI  - Takayasu's arteritis with pyoderma gangrenosum and necrotizing vasculitis.

PMID- 19758384
TI  - Dermatological aspects of medicine: highly active antiretroviral therapy and the
      treatment of human immunodeficiency virus.
AB  - This is the sixth in a series of CPD articles aimed at reviewing the recent
      general medical literature relating to topics that may be of interest to
      dermatologists. In this issue the new classes of anti-retroviral drugs will be
      described in the context of the replication cycle of human immunodeficiency virus
      (HIV). The regimens of drug treatments and the more common side-effects including
      HIV-lipodystrophy syndrome will be discussed along with the recommendations for
      testing of people for HIV from new guidelines.

PMID- 19758385
TI  - Calcipotriol induces apoptosis in psoriatic keratinocytes.
AB  - In recent years, vitamin D3 analogues have become one of the most widely
      prescribed topical treatments for mild or moderate chronic plaque psoriasis.
      These molecules are effective and safe, but their exact mechanism of action is
      not completely understood. In vitro studies have shown that D3 analogues decrease
      proliferation and induce differentiation of keratinocytes, and have strong
      immunomodulating effects, but there are no conclusive data about apoptosis. The
      aim of this study was to evaluate differences in apoptotic response between
      lesional and perilesional keratinocytes of patients with psoriasis before and
      after treatment with calcipotriol, a synthetic vitamin D3 analogue. Keratinocytes
      were isolated from psoriatic plaques including lesional and perilesional skin,
      and cultured. Cells were treated with calcipotriol for 20 h and examined under
      confocal microscopy after staining with propidium iodide. The number of apoptotic
      cells after incubation with calcipotriol was significantly higher in lesional
      than in perilesional keratinocytes (P < 0.05) or non-treated psoriatic
      keratinocytes (P < 0.05). In conclusion, calcipotriol seems to induce apoptosis
      in psoriatic keratinocytes.

PMID- 19758386
TI  - Successful treatment of dissecting cellulitis with ciprofloxacin.

PMID- 19758387
TI  - Lentigines following narrow-band ultraviolet B phototherapy for mycosis
      fungoides.

PMID- 19758388
TI  - Comparison of suction blister and carbon dioxide laser for recipient site
      preparation in epidermal grafting of segmental vitiligo.

PMID- 19758389
TI  - Cutaneous metastasis from gastric glomus tumour.
AB  - A 58-year-old man presented with a 4-month history of a rapidly enlarging
      asymptomatic tumour on the scalp vertex. Six years earlier, the patient had
      undergone subtotal gastrectomy for a presumed gastrointestinal stromal tumour
      (GIST). The tumour extended to the peritoneal surfaces, and foci of vascular
      invasion were also seen. No adjuvant treatment was given. Owing to diagnostic
      difficulties with the scalp tumour, a comparison was made with the previous
      gastric neoplasm. Both had features consistent with glomus tumour, which
      suggested a revised diagnosis of primary malignant gastric glomus tumour with
      subsequent cutaneous metastasis to the scalp some years later. This case
      highlights the features of glomus tumours and is a reminder that although rare,
      glomus tumours can be malignant and have the potential to metastasize. To our
      knowledge, this is the only reported case of a primary gastric glomus tumour with
      secondary metastasis to the skin.

PMID- 19758390
TI  - Academic research training for a nonacademic workplace: a case study of graduate
      student alumni who work in conservation.
AB  - Graduate education in conservation biology has been assailed as ineffective and
      inadequate to train the professionals needed to solve conservation problems. To
      identify how graduate education might better fit the needs of the conservation
      workplace, we surveyed practitioners and academics about the importance of
      particular skills on the job and the perceived importance of teaching those same
      skills in graduate school. All survey participants (n = 189) were alumni from the
      University of California Davis Graduate Group in Ecology and received thesis
      based degrees from 1973 to 2008. Academic and practitioner respondents clearly
      differed in workplace skills, although there was considerably more agreement in
      training recommendations. On the basis of participant responses, skill sets
      particularly at risk of underemphasis in graduate programs are decision making
      and implementation of policy, whereas research skills may be overemphasized.
      Practitioners in different job positions, however, require a variety of skill
      sets, and we suggest that ever-increasing calls to broaden training to fit this
      multitude of jobs will lead to a trade-off in the teaching of other skills. Some
      skills, such as program management, may be best developed in on-the-job training
      or collaborative projects. We argue that the problem of graduate education in
      conservation will not be solved by restructuring academia alone. Conservation
      employers need to communicate their specific needs to educators, universities
      need to be more flexible with their opportunities, and students need to be better
      consumers of the skills offered by universities and other institutions.

PMID- 19758391
TI  - Habitat split as a cause of local population declines of amphibians with aquatic
      larvae.
AB  - Most amphibian species have biphasic life histories and undergo an ontogenetic
      shift from aquatic to terrestrial habitats. In deforested landscapes, streams and
      forest fragments are frequently disjunct, jeopardizing the life cycle of forest
      associated amphibians with aquatic larvae. We tested the impact of habitat split-
      defined as human-induced disconnection between habitats used by different life
      history stages of a species--on four forest-associated amphibian species in a
      severely fragmented landscape of the Brazilian Atlantic Forest. We surveyed
      amphibians in forest fragments with and without streams (referred to as wet and
      dry fragments, respectively), including the adjacent grass-field matrix. Our
      comparison of capture rates in dry fragments and nearby streams in the matrix
      allowed us to evaluate the number of individuals that engaged in high-risk
      migrations through nonforested habitats. Adult amphibians moved from dry
      fragments to matrix streams at the beginning of the rainy season, reproduced, and
      returned at the end of the breeding period. Juveniles of the year moved to dry
      fragments along with adults. These risky reproductive migrations through
      nonforested habitats that expose individuals to dehydration, predation, and other
      hazards may cause population declines in dry fragments. Indeed, capture rates
      were significantly lower in dry fragments compared with wet fragments. Declining
      amphibians would strongly benefit from investments in the conservation and
      restoration of riparian vegetation and corridors linking breeding and nonbreeding
      areas.

PMID- 19758392
TI  - Trade-offs between species conservation and the size of marine protected areas.
AB  - Moving from single-species- to ecosystem-based management requires an
      understanding of how community-level attributes such as diversity change with
      area. We used survey data from bottom trawls to examine spatial patterns of
      species richness in U.S. Pacific coastal fishes. Specifically, we generated and
      compared species-area relationships (SARs) for species classified into several
      groups on the basis of maximum body size, trophic level, diet, maximum depth,
      geographic affinity, and taxonomic order. Because SARs among groups were not
      parallel and z values varied significantly for several groups, groups of species
      were under- or overrepresented (depending on the size of the area) relative to
      their proportions in the entire community (i.e., entire U.S. Pacific coast). In
      this way, differences in SARs help demonstrate trade-offs between species
      representation and coastal area and suggest strategies (such as targeting the
      protection of habitats and locations where a particular species or groups of
      species are maximized) that may minimize the size of marine protected areas
      (MPAs) but protect diversity at the level of the community and functional group.

PMID- 19758393
TI  - Extranodal NK / T-cell lymphoma, nasal type: new staging system and treatment
      strategies.
AB  - Extranodal NK/T-cell lymphoma (NTCL) is characterized by clinical heterogeneity
      based on clinical prognostic factors and survival outcome. NTCL subsets are
      classified as upper aerodigestive tract (UAT) NTCL or non-UAT NTCL; non-UAT has
      pathologic similarity to UAT-NTCL but is a clinically distinct subtype. Due to
      the clinical heterogeneity of NTCL, optimal treatment modalities and prognostic
      factors have been difficult to determine. Ann Arbor staging for lymphomas and the
      International Prognostic Index (IPI) have been used to predict prognosis for UAT
      NTCL; however, local tumor invasiveness (bony invasion or perforation or invasion
      of the overlying skin) is the most significant factor for poor outcomes in
      localized UAT-NTCL. Thus, a new staging system is proposed: limited disease
      (stage I/II UAT-NTCL without local tumor invasiveness) and extensive disease
      (stage I/II with local invasiveness or stage III/IV disease of UAT NTCL, and non
      UAT NTCL) based on treatment outcomes. NTCL is resistant to anthracycline-based
      chemotherapy, whereas non-anthracycline combination chemotherapy (such as
      ifosfamide, methotrexate, etoposide, and prednisolone) has an activity against
      NTCL as either a front-line or as a second-line treatment. The effectiveness of
      radiotherapy is evident in limited disease, but questionable in extensive
      disease.

PMID- 19758394
TI  - Engineered anti-CD20 antibodies with enhanced complement-activating capacity
      mediate potent anti-lymphoma activity.
AB  - One of the major issues in current antibody therapy is insufficient efficacy.
      Various biological factors relating to the host's immune system or tumor cells
      have been suggested to reduce the efficacy of anti-CD20 therapy in B-cell
      malignancies. In this study, we characterized the in vitro anti-lymphoma activity
      of anti-CD20 antibodies having a novel engineered heavy chain with enhanced
      complement-dependent cytotoxicity (CDC). Anti-CD20 antibodies having a variant
      heavy constant region of mixed IgG1/IgG3 isotype, which have previously been
      found to enhance CDC, were investigated for their in vitro CDC against lymphoma
      cells and whole blood B-cell depletion activity. Use of the variant constant
      region greatly increased the CDC of an anti-CD20 antibody having variable regions
      identical to those of rituximab to the level shown by an IgG1 antibody of
      ofatumumab. Although the whole blood assay showed different cytotoxicity patterns
      among individual blood donors, the CDC-enhancing variant of rituximab showed
      higher activity than the parent IgG1 and consistently showed maximized activity
      when further combined with antibody-dependent cellular cytotoxicity (ADCC)
      enhancing modification by fucose removal from Fc-linked oligosaccharides. In
      addition, the rituximab variant showed potent CDC against transfectant cells with
      lower CD20 expression and chronic lymphocytic leukemia-derived cell lines with
      higher complement regulatory proteins. These findings suggest that CDC
      enhancement, both alone and in combination with ADCC enhancement, increases the
      anti-lymphoma activity of anti-CD20 antibodies irrespective of individual
      differences in effector functions, and renders current anti-CD20 therapy capable
      of overcoming the potential resistance mechanisms.

PMID- 19758395
TI  - Platelet-derived growth factor beta receptor (PDGFRB) gene is rearranged in a
      significant percentage of myelodysplastic syndromes with normal karyotype.

PMID- 19758396
TI  - An unusual neurological complication of light chain amyloidosis.

PMID- 19758397
TI  - Systematic review: the effects of conservative and surgical treatment for obesity
      on gastro-oesophageal reflux disease.
AB  - BACKGROUND: Incidence rates of both obesity and gastro-oesophageal reflux disease
      (GERD) are increasing, particularly in the Western world. It has been suggested
      that GERD symptoms may be improved by weight reduction. AIM: To review the
      literature on the effect of various weight reducing modalities on manifestations
      of GERD in obese patients. METHODS: A literature search was performed using
      PubMed, EMBASE and the Cochrane Library, combining the words obesity and gastro
      oesophageal reflux with bariatric surgery, diet, lifestyle intervention and
      weight loss. RESULTS: With regard to diet/lifestyle intervention (conservative),
      four of seven studies reported an improvement of GERD. For Roux-en-Y gastric
      bypass, a positive effect on GERD was found in all studies, although this was
      mainly evaluated by questionnaires. In contrast, for vertical banded
      gastroplasty, no change or even an increase of GERD was noted, whereas the
      results for laparoscopic adjustable gastric banding were conflicting.
      CONCLUSIONS: Dietary and lifestyle intervention may improve GERD in obese
      patients; however, the most favourable effect is likely to be found after
      bariatric surgery, especially after Roux-en-Y gastric bypass. Future studies need
      to elucidate for which GERD patients laparoscopic adjustable gastric banding
      might have a beneficial effect and how they can be identified preoperatively.

PMID- 19758398
TI  - Clinical trial: oral ondansetron for reducing vomiting secondary to acute
      gastroenteritis in children--a double-blind randomized study.
AB  - BACKGROUND: Vomiting as a consequence of gastroenteritis frequently occurs in
      children. It is still debatable whether vomiting should be treated with
      antiemetic drugs. AIM: To investigate potential beneficial effects of ondansetron
      in treating vomiting during acute gastroenteritis. METHODS: A randomized, double
      blind, placebo-controlled trial was performed in our emergency departments.
      Children, aged 5 months to 8 years, were randomized to receive either ondansetron
      0.2 mg/kg or placebo at 8h intervals. The primary outcome measure was the
      frequency of emesis during an 8-h-period after enrollment. RESULTS: A hundred and
      nine patients were enrolled; 54 received placebo and 55 received ondansetron. As
      compared with the children who received placebo, children who received
      ondansetron were less likely to vomit both during the first 8-h follow-up in the
      emergency department [relative risk (RR): 0.33, 95% CI: 0.19-0.56, NNT: 2, 95%
      CI: 1.6-3.5], and during the next 24-h follow-up (RR: 0.15, 95% CI: 0.07-0.33,
      NNT: 2, 95% CI: 1.3-2.1). CONCLUSION: Ondansetron may be an effective and
      efficient treatment that reduces the incidence of vomiting from gastroenteritis
      during both the first 8 h and the next 24 h, and is probably a useful adjunct to
      oral rehydration.

PMID- 19758399
TI  - Regression of necrotizing scleritis in Wegener's granulomatosis after infliximab
      treatment.

PMID- 19758400
TI  - Intraocular pressure change after temporal clear corneal phacoemulsification in
      normal eyes.
AB  - PURPOSE: To evaluate short- and long-term intraocular pressure (IOP) changes
      after temporal clear corneal phacoemulsification in normal eyes. METHODS: The
      charts of 266 consecutive non-glaucoma patients who underwent uneventful cataract
      surgery were reviewed. We recorded preoperative and postoperative (1 day, 1 week,
      1 month, 3 months, 6 months, 1 year and 2 years) IOP measurements as well as
      anatomical properties obtained using Zeiss Humphrey IOL Master (Zeiss Meditech,
      Dublin, California, USA). RESULTS: Mean IOP reduction after cataract surgery was
      8.2%, 4.6%, 6.7% and 7.8% at 3 months, 6 months, 1 year and 2 years,
      respectively. Lens thickness was the only anatomical characteristic that
      correlated significantly with IOP decrease after surgery. CONCLUSION: Temporal
      clear corneal phacoemulsification results in a decrease in postoperative IOP that
      persists for 2 years following surgery.

PMID- 19758401
TI  - Angiotensin receptors in the eyes of arterial hypertensive rats.
AB  - PURPOSE: The aim of the present study was to determine whether the eye tissues of
      arterial hypertensive rats evince expression of angiotensin receptors (AT(1) and
      AT(2)) as well as the novel Mas receptor, whose endogenous ligand is vasorelaxing
      Angiotensin (1-7) [Ang (1-7)]. METHODS: Enucleated eyes from spontaneously
      hypertensive rats (SHR) and double transgenic rats harbouring human renin and
      angiotensinogen genes (dTGR) and their normotensive controls were used. Half of
      the rats were pretreated orally with an Angiotensin II (Ang II) type 1 receptor
      blocker (ARB). The eyes were snap-frozen in isopentane at -40 degrees and stored
      at -70 degrees for subsequent reverse transcriptase polymerase chain reaction (RT
      PCR) analysis or in vitro autoradiography. RESULTS: The mRNA expression of AT(1a)
      and AT(2) as well as the novel Mas receptor was detected in all rat groups, being
      markedly higher in the retina than in the ciliary body. dTGR had significantly
      more receptors than SHR, but no direct relation to blood pressure level was seen.
      According to the autoradiography, treatment with ARB blocked a part of AT(1)
      receptors but had no clear effect on AT(2) receptors. CONCLUSION: The novel Mas
      receptor was found by RT-PCR in eye tissue for the first time. Its specific
      ligand, Ang (1-7), may be involved in the regulation of intraocular pressure--as
      recently demonstrated by us--and in the pathogenesis of retinal diseases as a
      counter-regulatory component for the vascular and proliferative actions of Ang
      II. The results suggest that the density of AT(1) receptors in the eye is
      independent of the blood pressure level of the animal.

PMID- 19758402
TI  - Non-vitrectomizing vitreous surgery for premacular haemorrhage.
AB  - PURPOSE: We report three cases illustrating an alternative treatment option for
      premacular haemorrhage. METHODS: This retrospective interventional case study
      included three eyes in three patients with premacular haemorrhage caused by
      idiopathic thrombocytopenic purpura in the first case, trauma in the second case
      and retinal arterial macroaneurysm in the third case. All patients underwent non
      vitrectomizing vitreous surgery. Visual acuity as well as slit-lamp and indirect
      ophthalmoscopic examinations were performed pre- and postoperatively to evaluate
      the resolution of premacular haemorrhage and changes in lenticular opacity.
      RESULTS: At postoperative day 1, visual acuity had improved from counting fingers
      (CF) to 6/12 in case 1, from CF to 6/20 in case 2 and from CF to 3/60 in case 3.
      Examination of the fundus showed resolution of the premacular haemorrhage with
      mild vitreous haemorrhage in all cases. Final best corrected visual acuities were
      6/6, 6/7.5 and 6/15, respectively. The lens remained clear in two of two phakic
      eyes at the last follow-up visit. CONCLUSIONS: In these selected cases, non
      vitrectomizing vitreous surgery was a useful and safe alternative for the
      treatment of premacular haemorrhage.

PMID- 19758403
TI  - Glaucoma in aphakic and pseudophakic eyes following surgery for congenital
      cataract in the first year of life.
AB  - PURPOSE: To determine the incidence and risk factors for glaucoma in pseudophakic
      and aphakic eyes following surgery for congenital cataract within the first year
      of life. METHODS: We conducted a review of all cataract surgery performed at our
      unit over a 23-year period. Age at surgery, corneal diameter, intraocular lens
      implantation, presence of persistent foetal vasculature and visual axis
      opacification (VAO) were documented. Time to development of glaucoma, management
      and outcome were determined. One eye was selected randomly for analysis in cases
      of bilateral cataract. RESULTS: Duration of follow-up was significantly longer (p
      < 0.001) in the aphakic (113 +/- 69 months) compared to the pseudophakic group
      (56 +/- 44 months). Age at surgery was significantly less (p = 0.01) in the
      aphakic group. The incidence of glaucoma was significantly greater (p = 0.02) in
      the aphakic (15 eyes, 33%) compared to the pseudophakic (seven eyes, 13%) group.
      Each eye that developed glaucoma underwent cataract extraction aged < or = 2.5
      months. Analysis of all eyes that underwent surgery aged < or = 2.5 months
      revealed no statistical difference (p = 0.08) in the incidence of glaucoma.
      Smaller corneal diameter and VAO were not associated with increased risk of
      glaucoma development. Ahmed valves proved effective in controlling intraocular
      pressure but visual outcome was poor in the majority of cases. CONCLUSION:
      Surgery for congenital cataract at an early age increases the risk of glaucoma
      development, regardless of whether the eye is aphakic or pseudophakic.
      Intraocular pressure control with Ahmed valves is frequently required.
      Glaucomatous damage and dense amblyopia contribute to poor visual outcome in
      these eyes.

PMID- 19758404
TI  - Caries frequency and distribution in an early medieval Avar population from
      Austria.
AB  - OBJECTIVE: The aim of this study was to determine frequency and distribution of
      dental caries in an early medieval Avar population from Central Europe, namely
      Vienna. METHODS: The evaluation of caries was carried out in an anthropological
      sample consisting of the remains of 136 individuals and included 2215 permanent
      teeth. Age and sex estimations were based on dental development and on skeletal
      ageing methods. The presence of dental caries was determined according to
      clinical aspects using a dental probe. RESULTS: The frequency of ante mortem
      tooth loss in the sample was 23.8%; the total caries frequency was calculated as
      14.9%. The highest caries rate was recorded in the second mandibular molar
      (34.6%). The most affected tooth surface was found to be the root with 12.7%,
      followed by the approximal surface with 8.6%, but only 7.7% of the occlusal
      surfaces were affected by caries. CONCLUSION: This study revealed that Avars
      suffered from higher caries rates than most other medieval European populations,
      but experienced a similar dental caries distribution. Attrition of the occlusal
      surface resulting from a diet containing abrasive particles with accompanying
      posteruptive tooth movement is considered the major factor causing this premodern
      caries pattern.

PMID- 19758405
TI  - Langerhans cell histiocytosis: oral/periodontal involvement in adult patients.
AB  - OBJECTIVE: Langerhans cell histiocytosis (LCH) is a clonal proliferative
      multisystem disease. Although bone and mucosae have been classified as non-risk
      organs, their involvement may increase the risk of disease progression. Oral and
      periodontal lesions are burdened with a significant impairment of quality of life
      for associated signs, symptoms and loss of function. Most of information regards
      paediatric disease; the disease in adults has received limited attention.
      SUBJECTS AND METHODS: A total of 31 adult patients affected by immuno
      histopathology confirmed LCH have been prospectively examined; attention was paid
      to the occurrence and characterization of oral lesions. RESULTS: Twelve patients
      developed oral lesions. Posterior regions of jawbones were always affected; the
      involvement of anterior regions was not constant. Unifocal oral involvement was
      significantly associated with multisystemic disease while multifocal lesions were
      associated with unisystemic disease. Oral disease presented with soft tissue
      ulcers (50% of cases), gingival bleeding (66.7%), pain (83.4%), periodontal
      damage (50%), tooth mobility (16.7%), non-healing extraction socket (8.3%); 41.6%
      of patients complained of negative outcomes on quality of life. Oral lesions were
      easily handled with local measures. CONCLUSIONS: Posterior regions require
      attention; single oral lesions may be part of multisystemic disease; oral and
      periodontal lesions may be early signs of disease reactivation.

PMID- 19758406
TI  - Immune reconstitution inflammatory syndrome after highly active antiretroviral
      therapy: a review.
AB  - The use of highly active antiretroviral therapy (HAART) in the management of
      human immunodeficiency virus (HIV) restores immune responses against pathogens
      and has greatly decreased mortality. However, in about 25% to 35% of patients
      receiving HAART, the reconstituted immune system leads to a pathological
      inflammatory response, commonly known as immune reconstitution inflammatory
      syndrome (IRIS), which causes substantial short-term morbidity or even mortality.
      Although we have gleaned some knowledge on IRIS in the past few years, a number
      of unanswered questions remain. In this review, we discuss the definition,
      diagnostic criteria, pathogenesis, risk factors, clinical spectrum including oral
      manifestations, and management of IRIS.

PMID- 19758407
TI  - Clinical and psychological characteristics of TMD patients with trauma history.
AB  - OBJECTIVE: The purpose of this study was to investigate clinical and
      psychological characteristics of temporomandibular disorders (TMD) patients with
      trauma history. MATERIALS AND METHODS: The clinical and psychological
      characteristics of 34 TMD patients with trauma history were compared with those
      of 340 TMD patients without trauma history. Craniomandibular index (CMI) was used
      for clinical characteristics of TMD patients. Symptom severity index (SSI) was
      used to assess the multiple dimensions of pain. Symptom checklist-90-revision
      (SCL-90-R) was used for psychological evaluation. RESULTS: Temporomandibular
      disorders patients with trauma history displayed significantly higher CMI and
      palpation index. TMD patients with trauma history also exhibited higher values in
      duration, sensory intensity, affective intensity, tolerability, scope of symptom,
      and total SSI score. In addition, these patients showed significantly higher
      values in symptom dimensions of somatization, depression, anxiety, phobic
      anxiety, and paranoid ideation. Among the symptom dimensions of SCL-90-R,
      somatization showed the most significant correlations with CMI and SSI.
      CONCLUSIONS: Temporomandibular disorders patients with trauma history displayed
      more severe subjective, objective, and psychological dysfunction than those
      without trauma history. Pain of myogenous origin, history of physical trauma, and
      psychosocial dysfunction were all closely related.

PMID- 19758408
TI  - Na(+)/H(+) antiporter activity of the SOS1 gene: lifetime imaging analysis and
      electrophysiological studies on Arabidopsis seedlings.
AB  - Based on sequence analysis, the salt overly sensitive (SOS1) gene has been
      suggested to function as a Na(+)/H(+) antiporter located at the plasma membrane
      of plant cells, being expressed mostly in the meristem zone of the root and in
      the parenchyma cells surrounding the vascular tissue of the stem. In this study,
      we compared net H(+) and Ca(2+) fluxes and intracellular pH and [Ca(2+)](cyt) in
      the root meristem zone of Arabidopsis wild-type (WT) and sos mutants before and
      after salt stress. In addition, we studied the effect of pretreatment with
      amiloride (an inhibitor of Na(+)/H(+) antiporters) on net ion fluxes,
      intracellular pH and intracellular Ca(2+) activity ([Ca(2+)](cyt)) in WT plants
      and sos1 mutants before and after salt stress. Net ion fluxes were measured using
      microelectrode ion flux estimation (MIFE) and intracellular pH and [Ca(2+)](cyt)
      using fluorescence lifetime imaging microscopy (FLIM) techniques. During the
      first 15 min after NaCl application, sos1 mutants showed net H(+) efflux and
      intracellular alkalinization in the meristem zone, whereas sos2 and sos3 mutants
      and WT showed net H(+) influx and slight intracellular acidification in the
      meristem zone. Treatment with amiloride led to intracellular acidification and
      lower net H(+) flux in WT plants and to a decrease in intracellular Ca(2+) in WT
      and sos1 plants. WT plants pretreated with amiloride did not show positive net
      H(+) flux and intracellular acidification. After NaCl application, internal pH
      shifted to higher values in WT and sos1 plants. However, absolute values of H(+)
      fluxes were higher and internal pH values were lower in WT plants pretreated with
      amiloride compared with sos1 mutants. Therefore, the SOS1 transporter is involved
      in H(+) influx into the meristem zone of Arabidopsis roots, or it may function as
      a Na(+)/H(+) antiporter. Amiloride affects SOS1 and other Na(+)/H(+) antiporters
      in plant cells because of its ability to decrease the H(+) gradient across the
      plasma membrane.

PMID- 19758409
TI  - Activity pattern of swallowing-related muscles, food properties and body position
      in normal humans.
AB  - Activity patterns of the swallowing-related muscles were examined in normal
      subjects at different four body positions during swallowing of foods with
      different textural properties. Surface electromyograms were recorded from two
      muscle groups, the anterior tongue and suprahyoid muscles. The T(P) technique we
      developed was applied to the electromyograms for quantitative analysis of the
      activity patterns. Three test foods were prepared by dissolving 2.0% (low), 5.7%
      (middle) and 9.1% (high concentration) of a thickening agent into distilled
      water. Each subject was delivered randomly, one of the test foods to swallow at
      one of the four body positions i.e. horizontal supine, 30 degrees inclined, 60
      degrees inclined and upright. In this study, T(50) values were calculated in
      activity data of the two muscle groups, and the T(50) values were statistically
      examined analysis of variance with a linear model including four fixed effects of
      'concentrations', 'body positions', 'subjects' and 'sessions'. Three major
      findings obtained were that (i) the activity pattern of the anterior tongue was
      altered from a decrementing discharge pattern to an incrementing discharge
      pattern by shifting from the upright to the horizontal supine position, (ii) the
      activity pattern of the suprahyoid muscles was altered from a decrementing
      discharge pattern to an incrementing discharge pattern by shifting from the low
      concentration food to the higher ones and (iii) two subgroups were detected in
      subjects with the significant effects of 'concentrations' and 'body positions'.
      These findings lead a conclusion that activity patterns of the swallowing-related
      muscles are affected by food properties and body positions.

PMID- 19758410
TI  - Clinical study on the insertion torque and wireless resonance frequency analysis
      in the assessment of torque capacity and stability of self-tapping dental
      implants.
AB  - Resonance frequency (RF) analysis is a non-invasive, objective and sensitive
      technique developed for implantology where it measures the stability of the
      implant in osteotomy site. Although many studies were performed by the previous
      electronic version of RF analyzer, a very limited number of studies were carried
      out with the new magnetic wireless version. The aim of the study was to evaluate
      the relation between insertion torques, primary and secondary stability of self
      tapping tapered implant systems. Thirteen subjects were treated with 42
      endosseous implants using two-stage surgical procedure. The maximal insertion
      torque values were recorded prior to RF analysis during surgery. Six months after
      surgery, the secondary stability values were measured by the RF analysis. The
      average maximal insertion torque and primary and secondary magnetic RF values
      were 33 +/- 11 N cm and 66 +/- 12 ISQ and 71.9 +/- 6 ISQ for 42 implants
      respectively. The correlation between insertion torque and RF values were
      indicated to be statistically significant (P < 0.01). Significantly higher
      maximal insertion torque, and primary and secondary magnetic RF values were
      achieved in mandibular sites compared with maxillary areas (P < 0.01). No
      significant differences were measured for all parameters when both systems were
      compared with each other (P > 0.05). There was a strong correlation between the
      insertion torque, primary and secondary magnetic RF values of self-tapping
      tapered endosseous implant used. Further studies are needed to understand the
      impact of the wireless magnetic RF analysis technique in clinics.

PMID- 19758411
TI  - Histological evaluation of alveolar ridge augmentation using injectable calcium
      phosphate bone cement in dogs.
AB  - Alveolar ridge augmentation is an important procedure to restore tooth loss.
      Several types of graft materials have been used for augmenting the alveolar
      ridge. An injectable calcium phosphate cement (CPC) has been applied to
      periodontal bone defects and has shown favourable results. Thus, this CPC may
      work as an effective graft material for alveolar ridge augmentation. The aim of
      this study was to evaluate the effectiveness of the CPC for large-scaled (about 7
      x 8 x 6 mm) ridge augmentation in dogs. Alveolar ridge defects were created
      bilaterally in the maxilla of six beagle dogs. The CPC was applied to one of the
      bilateral maxillary defects. The untreated defect on the contralateral side
      served as control. The animals were sacrificed at 6 months after surgery and
      decalcified histological specimens of the alveolar ridge were prepared
      histometrically and evaluated under a light microscope. Newly formed and
      reconstructed alveolar ridges covering the CPC were observed in all experimental
      sites. In the control sites, only slight newly bone formation was observed.
      Histomorphometrical analysis indicated that the CPC grafted group exhibited
      significantly (P = 0.0001) increased area and height in new bone formation
      compared with those of the control group. The results indicate that the CPC
      appears to be an effective material for alveolar ridge augmentation and may act
      as a space maintainer to conduct new bone formation.

PMID- 19758412
TI  - Application of fluoride iontophoresis to improve remineralization.
AB  - Iontophoresis is generally used to maximize the therapeutic action of drugs in
      medicine. This technique can be used to improve the remineralization effect of
      topical fluoride applications in dentistry. The aim of this study was to compare
      the remineralization effect of fluoride iontophoresis (FI) with the conventional
      fluoride application (CFA) method in vitro. Sixty bovine enamel specimens were
      divided into three groups: no fluoride treatment, CFA and FI. Fluoride was
      applied to the demineralized specimens for 4 min in each experimental group. The
      types of fluoride system used for application were 1.23% acidulated phosphate
      fluoride gel (12 300 p.p.m. F, pH 3.5) and 2% sodium fluoride solution (9050
      p.p.m. F, pH 7) in the experimental groups. All the specimens were then placed in
      a remineralizing solution for 24 h. This cycle was repeated five times. An
      iontophoresis device (0.4 mA, 12 V) was used in the FI groups. The efficacy of
      this technique was evaluated by measuring changes in the surface microhardness
      and lesion depth of the specimens using confocal laser scanning microscope
      (CLSM). Data were analysed using anova and Tukey's post hoc test (P < 0.05).
      Although the FI groups showed higher DeltaVHN than the CFA groups, there were no
      significant differences between these fluoride application methods (P > 0.05).
      When the lesion depth was measured using CLSM imaging, there was also no
      significant difference between the FI and CFA groups (P > 0.05). In conclusion,
      FI was not significantly superior to CFA in terms of the remineralization effect.

PMID- 19758413
TI  - Chronic haemolytic anaemia because of pyruvate kinase (PK) deficiency in a child
      heterozygous for haemoglobin S and no clinical features of sickle cell disease.

PMID- 19758414
TI  - RNA interference-mediated knock-down of Bla g 1 in the German cockroach,
      Blattella germanica L., implicates this allergen-encoding gene in digestion and
      nutrient absorption.
AB  - We used RNA interference (RNAi) to silence the expression of a gene encoding Bla
      g 1, a human allergen produced by the German cockroach, Blattella germanica L.,
      to study its function in cockroach physiology. Females injected with 1 microg of
      double-stranded RNA contained 64% less Bla g 1 protein and Bla g 1 mRNA abundance
      was reduced by 91.4% compared to sham-injected females. Bla g 1 knockdown slowed
      the pace of weight gain, midgut growth, and colleterial gland and basal oocyte
      maturation, resulting in delayed egg case formation and lower fecundity.
      Exogenous juvenile hormone treatments rescued reproduction in RNAi-treated
      females, suggesting that Bla g 1 silencing lowered endogenous juvenile hormone,
      probably by reducing food intake and nutrient absorption.

PMID- 19758415
TI  - Towards a proposal for assessment of blinding success in clinical trials: up-to
      date review.
AB  - The CONSORT statement recommended that investigators should clearly report which
      key trial persons were blinded to treatment allocation and test for the success
      of blinding. Clinical researchers, however, more often than not overlook the
      assessment of the success of blinding. The severe under-reporting on the success
      of blinding may improve with awareness of existing quantitative methods. The two
      statistical methods, James' blinding index (BI) and Bang's BI, are currently
      available. Subjects could be asked to guess their treatment assignment, possibly
      with an option to express the degree of certainty. Assessments of blinding at
      various points may serve different purposes, i.e. to evaluate comparability
      between experimental versus control treatments before the trial by the third
      party; to examine further comparability and credibility of the control treatment
      and patients' expectation about treatment received in early stage of the trial,
      and to summarize the overall maintenance of the blinding success at the end of
      the trial. In this article, we review BIs and how to use these methods along with
      discussion of other issues in blinding assessment and reporting. We contend the
      two BIs that were independently developed but carry complementary properties
      would characterize blinding behaviours in clinical trials qualitatively as well
      as quantitatively, and may also shed some lights on the interpretation of the
      study findings. Finally we urge the Item 11b of the CONSORT statement to be
      revised to require the assessment/reporting of blinding success for all trials
      that adopt blinding schemes.

PMID- 19758416
TI  - Reactive oxygen species promote angiogenesis in the infarcted rat heart.
AB  - The purpose of this study was to determine whether reactive oxygen species (ROS)
      promote cardiac angiogenesis following myocardial infarction (MI) and contribute
      to cardiac repair. Rats with MI were treated with or without antioxidants, tempol
      and apocynin. Hearts of these rats were collected at days 2, 4, 7 and 14 post-MI.
      We examined the spatial and temporal relationship between oxidative stress and
      angiogenesis as well as the potential regulation of ROS in cardiac angiogenesis.
      We found: (i) following MI, gp91(phox), a subunit of NADPH oxidase, a key enzyme
      for ROS production, was significantly increased in the border zone at day 2,
      followed by the infarcted myocardium at day 4, peaked at day 7 and declined at
      day 14, while superoxide dismutase was significantly reduced; (ii)
      malondialdehyde, a marker of oxidative stress, was significantly increased in the
      infarcted myocardium at day 7; (iii) pre-existing blood vessels in the infarcted
      myocardium underwent necrosis post-MI, whereas newly formed vessels appeared at
      the border zone at day 4, and then extended into the infarcted myocardium, where
      microvascular density peaked at day 7 and (iv) antioxidant treatment
      significantly reduced microvascular density in the infarcted myocardium at day 7.
      These observations suggest that following MI, angiogenesis is mostly active in
      the infarcted myocardium in the first week, which is temporally and spatially
      coincident with enhanced ROS. Suppression of angiogenesis by antioxidants
      indicates that ROS promote angiogenesis in the infarcted myocardium and
      contribute to cardiac repair. Further studies are required to determine the
      mechanisms responsible for ROS-mediated cardiac angiogenesis.

PMID- 19758417
TI  - Gamma-delta T cell subsets are differentially associated with granuloma
      development and organization in a bovine model of mycobacterial disease.
AB  - The characteristic lesion in bovine tuberculosis is well-organized respiratory
      granulomas. This is typically associated with a strong T-helper 1 biased cell
      mediated immune response and eventual containment of the infection. In bovine
      paratuberculosis, the classic lesion is unorganized granulomatous intestinal
      inflammation. Clinical paratuberculosis is associated with a T-helper 2 biased
      humoral immune response and eventual death because of inability of the host to
      contain the infection. Recent reports have suggested that gamma-delta
      (gammadelta) T cells play a significant role in granuloma development and/or
      maintenance during initial stages of infection and may influence the subsequent
      adaptive immune response. The objective of this study was to use an in vivo
      bovine model to evaluate gammadelta T cells during the early host immune response
      to mycobacterial infection. We used immunofluorescent staining, hyperspectral
      microscopy, and computerized assisted morphometry to evaluate staining and
      distribution of gammadelta T cells during development of organized and
      unorganized granulomas. Our data suggest that bovine gammadelta T cell subsets
      are differentially recruited to early infection sites, and may be instrumental
      during the initial antimycobacterial host immune response as well as for
      granuloma organization.

PMID- 19758418
TI  - PDEs1-5 activity and expression in tissues of cirrhotic rats reveal a role for
      aortic PDE3 in NO desensitization.
AB  - Liver cirrhosis is associated with increased nitric oxide (NO) production in the
      vasculature. We have previously demonstrated that aorta from rats with liver
      cirrhosis have a reduced relaxant response to NO donors that is corrected by
      DMPPO, a PDE5-specific inhibitor. Vasodilator responses to DMPPO itself were also
      reduced in rings from cirrhotic rats. These results supported previous
      suggestions that upregulation of PDE5 in liver cirrhosis might contribute to
      renal sodium retention, and consequently modulate vascular reactivity in the
      context of increased NO production (Tahseldar-Roumieh et al. in Am. J. Physiol.
      Heart Circ. Physiol. 290, H481-H488, 2006). Here, we investigated the possible
      alteration in activity and expression of cyclic nucleotide phosphodiesterase PDE1
      PDE5 in kidney and vascular tissues in rats 4 weeks after bile duct ligation. The
      kidney of rats with cirrhosis had increased activity of PDE1 and PDE4 but not
      PDE5, and increased expression of PDE1A. Unexpectedly and interestingly, there
      was no change in cirrhotic aorta PDE5, but an increase in PDE3 and PDE4 activity
      associated with increased expression of PDE3A and PDE3B. Cilostamide, a specific
      PDE3 inhibitor, corrected the decreased response to an NO donor in isolated aorta
      from cirrhotic rats, suggesting that the difference in response to NO donors was
      due to differences in PDE3-induced hydrolysis of cGMP or to cGMP-induced
      inhibition of PDE3, rather than to differences in PDE5 contribution. In
      conclusion, these changes in PDE isozymes could greatly contribute to NO
      desensitization and to the regulation of vascular and renal function in liver
      cirrhosis.

PMID- 19758419
TI  - A physiologically relevant atherogenic diet causes severe endothelial dysfunction
      within 4 weeks in rabbit.
AB  - A physiological atherogenic human diet consists of 0.1% cholesterol, fat, as well
      as high levels of methionine, which is the precursor to homocysteine. The
      pathological effects of a diet enriched with physiologically high levels of
      cholesterol, methionine and fat over a short period on the aorta are unknown. In
      this regard, we sought to determine the effects of a 0.1% cholesterol diet in
      combination with a 1% methionine over a 4-week period on endothelial function and
      artery pathology and the expression of endothelial nitric oxide synthase as well
      as nitrosative stress by nitrotyrosine (NT), oxidative stress by heat shock
      protein 70 (HSP70) and endoplasmic reticulum stress by glucose regulated protein
      78 (GRP78). Rabbits were fed for 4 weeks a diet supplemented with 1% methionine +
      0.1% cholesterol + 5% peanut oil (MC). The endothelial function of the abdominal
      aorta was examined using organ bath techniques, atherosclerosis determined in
      each artery by microscopy and eNOS, NT, GRP78 and HSP70 by standard
      immunohistochemistry. Endothelium dependent relaxation in response to
      acetylcholine significantly decreased by 63% at 1 muM acetylcholine (P < 0.001)
      compared with control arteries. There was no evidence of atherosclerosis
      formation in any artery studied, however, eNOS, NT and GRP78 was clearly present
      in all arteries studied but HSP70 was not easily detectable. Severe endothelial
      dysfunction is present in the abdominal aorta of rabbits within 4 weeks of
      physiological dietary manipulation, possibly due to NT formation and endoplasmic
      reticulum stress. This model could be used to study the early onset of
      endothelial dysfunction prior to the initiation of atherosclerosis.

PMID- 19758420
TI  - Correlation between NGF/TrkA and microvascular density in human pterygium.
AB  - Pterygium is a surface ocular lesion that is associated with chronic UV exposure.
      The primary effect is a solar actinic elastosis within the stroma. All the other
      changes are secondary. Pterygium is characterized by proliferation, inflammatory
      infiltrates, fibrosis, angiogenesis and extracellular matrix breakdown. The aim
      of this study was to correlate microvascular density and nerve growth factor
      (NGF)/NGF-receptor transmembrane tyrosine kinase (TrkA) expression in endothelial
      cells in human pterygium. Specimens of human pterygium obtained from 30 patients
      who had undergone surgical excision and of 10 normal bulbar conjunctiva were
      investigated immunohistochemically by using anti-CD31, anti-NGF and anti-TrkA
      antibodies. Results showed that endothelial cells in human pterygium are
      immunoreactive to both NGF and its receptor TrkA, and that this immunoreactivity
      is correlated to microvascular density. The results of this study suggest that an
      autocrine loop between NGF and its receptor TrkA is activated in pterygium and
      that it is involved in the angiogenic response taking place in this pathological
      condition. These data are in accord with recent evidences, which have clearly
      established that NGF plays a role as an angiogenic factor in several pathological
      conditions. Understanding the mechanism of angiogenesis in pterygium provides a
      basis for a rational approach to the development of anti-angiogenic therapy in
      patients affected by this disease.

PMID- 19758421
TI  - Influenza A(H1N1) and infection control guidelines for optometrists.
AB  - The emergence of a novel influenza A virus (Influenza A[H1N1]), which has not
      circulated previously in humans, has led to the first global influenza pandemic
      in 41 years. Influenza A(H1N1), commonly called 'swine flu', is a novel influenza
      virus made up of porcine, avian and human genes, and preferentially infects
      younger people. Although Influenza A(H1N1) does not appear to be likely to cause
      as many fatalities as previous influenza pandemics, attempts to contain it are
      necessary because people whose health is already compromised through underlying
      chronic medical conditions are at risk of death if they contract the virus. In
      addition, pregnant women who become infected are at increased risk of
      complications. This paper provides figures on the number of cases of Influenza
      A(H1N1) and deaths associated with this virus in Australia (using World Health
      Organization and Australian Government figures) and discusses infection control
      measures that optometrists should put in place for themselves, their staff and
      their patients, in the event that there is suspicion of Influenza A(H1N1)
      infection. Measures include isolating those who display symptoms indicative of
      influenza, use of surgical masks (P2 [N95]) by the infected person, frequent hand
      washing, appropriate cough and sneeze etiquette, disposal of used tissues and
      rescheduling of non-urgent appointments for those thought to be infected. Any
      staff members who need to be closer than one metre to the infected person should
      also use personal protective equipment (for example, surgical masks, goggles or
      safety spectacles, gowns and gloves). The current evidence indicates that
      Influenza A(H1N1) should be treated by optometrists as another type of flu. As
      with other forms of influenza, following basic infection control guidelines will
      help reduce the spread of infection in optometric practices and within the
      community.

PMID- 19758422
TI  - Size-dependent foraging gene expression and behavioral caste differentiation in
      Bombus ignitus.
AB  - BACKGROUND: In eusocial hymenopteran insects, foraging genes, members of the cGMP
      dependent protein kinase family, are considered to contribute to division of
      labor through behavioral caste differentiation. However, the relationship between
      foraging gene expression and behavioral caste in honeybees is opposite to that
      observed in ants and wasps. In the previously examined eusocial Hymenoptera,
      workers behave as foragers or nurses depending on age. We reasoned that
      examination of a different system of behavioral caste determination might provide
      new insights into the relationship between foraging genes and division of labor,
      and accordingly focused on bumblebees, which exhibit size-dependent behavioral
      caste differentiation. We characterized a foraging gene (Bifor) in bumblebees
      (Bombus ignitus) and examined the relationship between Bifor expression and size
      dependent behavioral caste differentiation. FINDINGS: A putative open reading
      frame of the Bifor gene was 2004 bp in length. It encoded 668 aa residues and
      showed high identity to orthologous genes in other hymenopterans (85.3-99.0%). As
      in ants and wasps, Bifor expression levels were higher in nurses than in
      foragers. Bifor expression was negatively correlated with individual body size
      even within the same behavioral castes (regression coefficient = -0.376, P <
      0.001, all individuals; -0.379, P = 0.018, within foragers). CONCLUSION: These
      findings indicate that Bifor expression is size dependent and support the idea
      that Bifor expression levels are related to behavioral caste differentiation in
      B. ignitus. Thus, the relationship between foraging gene expression and
      behavioral caste differentiation found in ants and wasps was identified in a
      different system of labor determination.

PMID- 19758423
TI  - Pulmonary stenosis development and reduction of pulmonary arterial hypertension
      in atrioventricular septal defect: a case report.
AB  - A 24-year-old patient was admitted for dyspnoea and syncope. He had a previous
      history of complete atrio-ventricular septal defect and trisomy 21. At the age of
      6 months, in 1984, cardiac catheterization revealed a quasi-systemic pulmonary
      arterial hypertension with a bidirectional shunt corresponding to an Eisenmenger
      syndrome. Corrective cardiac surgery was not performed at this time because
      surgical risk was considered too high. Until the age of 20 years old, he showed
      few symptoms while under medical treatment. But since 2006, his functional status
      became worse with an increased dyspnoea, syncopes, and severe cyanosis. In these
      conditions, haemodynamic parameters have been re-evaluated in 2006 and 2008.They
      highlighted a late and progressive development of a valvular and infundibular
      pulmonary stenosis leading to a normalisation of pulmonary arterial pressures. At
      the age of 24 , the patient underwent corrective cardiac surgery which was
      successful. Late development of both infundibular and valvular pulmonary stenosis
      have not been described before in non operated congenital ventricular septal
      defects, but development of one or the other abnormality would be found in 8% of
      patients. The physiopathological mechanism of this obstruction is unclear.
      Nevertheless, in unoperated congenital cardiac shunt lesions, reversibility of
      severe pulmonary arterial hypertension should be reconsidered and re-assessed
      during follow up.

PMID- 19758424
TI  - Assessment of angle velocity in girls with adolescent idiopathic scoliosis.
AB  - BACKGROUND: Although it has been demonstrated that the peak height velocity (PHV)
      is a predictive factor of progression in adolescent idiopathic scoliosis (AIS),
      little is known about the usefulness of angle progression in clinical practice.
      The purpose of this study was to establish a relationship between height and
      angle velocities, as well as to determine if peak angle velocity (PAV) occurs at
      the same time than PHV. METHODS: A retrospective study of a cohort of girls with
      idiopathic scoliotic curves greater than 10 degrees . Data of 132 girls who
      participated in a previous retrospective study about growth in AIS were used to
      calculate height and angle velocities. Relationship between height and angle
      velocities was estimated by the use of a Linear Mixed Model. RESULTS: PHV and PAV
      take place simultaneously 1 year before menarche in progressive curves managed
      with a brace in AIS. Changes in angle velocity are influenced by changes in
      height growth velocity, in such a way that as from 6 months post-menarche, height
      growth velocity in this group of girls estimates curve progression velocity (beta
      coefficient -0.88, p = 0.04). CONCLUSION: As from 6 months post-menarche, there
      is an inverse relationship between height velocity and curve progression in the
      group of AIS girls with progressive curves managed with a brace. Because height
      velocity is decreasing from 1 year before menarche, this finding corroborates
      that at the end of puberty, there is still a risk of progression in this group of
      girls despite bracing. The assessment of both height and angle velocity might be
      useful in clinical practice at the time of assessing brace effectiveness and how
      long bracing has to be indicated.

PMID- 19758425
TI  - Is the association between acne and mental distress influenced by diet? Results
      from a cross-sectional population study among 3775 late adolescents in Oslo,
      Norway.
AB  - BACKGROUND: Several studies with conflicting findings have investigated the
      association between acne and mental health problems. Acne usually starts in
      adolescents, as does an increase in the prevalence of depression and anxiety.
      Recently, there has been more focus on the link between diet and acne and diet
      and mental health problems. The objective of this study is to investigate the
      association between acne and mental distress and to explore a possible influence
      of dietary factors on the relation. METHODS: A population-based cross-sectional
      study in Oslo of 18 or 19 year old adolescents. The participation rate was 80%.
      Acne was self-reported. To measure mental distress, the Hopkins Symptom Checklist
      10 was used. Diet and lifestyle variables were also collected by questionnaire
      and socio-demographic variables were obtained from Statistics Norway. RESULTS:
      The prevalence of acne was 14.4% among the males and 12.8% among the females. The
      mean score of mental distress increased when the severity of acne increased. In
      the crude analyses, the significant associations with acne among the males were:
      mental distress OR = 1.63, frequent consumption of chocolate/sweets OR = 1.40,
      frequent consumption of potato chips OR = 1.54. The significant crude
      associations with acne among the females were: mental distress OR = 2.16,
      infrequent consumption of raw vegetables OR = 1.41, non-Western background OR =
      1.77 and low family income OR = 2.14. No crude associations with acne were
      identified in either gender for the consumption of sugary soft drinks, fatty
      fish, cigarette smoking or alcohol. In adjusted models which included diet and
      socio-demographic variables, the association between acne and mental distress was
      unchanged for both males (OR = 1.68) and females (OR = 2.04), and between acne
      and infrequent consumption of raw vegetables among the females (OR = 1.38).
      CONCLUSION: Among late adolescents in Oslo, self-reported acne is significantly
      associated with mental distress and, among girls, with infrequent consumption of
      raw vegetables. Our finding does not support the hypothesis that dietary factors
      alter the relationship between acne and mental distress.

PMID- 19758426
TI  - Towards the prediction of essential genes by integration of network topology,
      cellular localization and biological process information.
AB  - BACKGROUND: The identification of essential genes is important for the
      understanding of the minimal requirements for cellular life and for practical
      purposes, such as drug design. However, the experimental techniques for essential
      genes discovery are labor-intensive and time-consuming. Considering these
      experimental constraints, a computational approach capable of accurately
      predicting essential genes would be of great value. We therefore present here a
      machine learning-based computational approach relying on network topological
      features, cellular localization and biological process information for prediction
      of essential genes. RESULTS: We constructed a decision tree-based meta-classifier
      and trained it on datasets with individual and grouped attributes-network
      topological features, cellular compartments and biological processes-to generate
      various predictors of essential genes. We showed that the predictors with better
      performances are those generated by datasets with integrated attributes. Using
      the predictor with all attributes, i.e., network topological features, cellular
      compartments and biological processes, we obtained the best predictor of
      essential genes that was then used to classify yeast genes with unknown
      essentiality status. Finally, we generated decision trees by training the J48
      algorithm on datasets with all network topological features, cellular
      localization and biological process information to discover cellular rules for
      essentiality. We found that the number of protein physical interactions, the
      nuclear localization of proteins and the number of regulating transcription
      factors are the most important factors determining gene essentiality. CONCLUSION:
      We were able to demonstrate that network topological features, cellular
      localization and biological process information are reliable predictors of
      essential genes. Moreover, by constructing decision trees based on these data, we
      could discover cellular rules governing essentiality.

PMID- 19758427
TI  - The Iranian version of 12-item Short Form Health Survey (SF-12): factor
      structure, internal consistency and construct validity.
AB  - BACKGROUND: The 12-item Short Form Health Survey (SF-12) as a shorter alternative
      of the SF-36 is largely used in health outcomes surveys. The aim of this study
      was to validate the SF-12 in Iran. METHODS: A random sample of the general
      population aged 15 years and over living in Tehran, Iran completed the SF-12.
      Reliability was estimated using internal consistency and validity was assessed
      using known groups comparison and convergent validity. In addition, the factor
      structure of the questionnaire was extracted by performing both exploratory
      factor analysis (EFA) and confirmatory factor analysis (CFA). RESULTS: In all,
      5587 individuals were studied (2721 male and 2866 female). The mean age and
      formal education of the respondents were 35.1 (SD = 15.4) and 10.2 (SD = 4.4)
      years respectively. The results showed satisfactory internal consistency for both
      summary measures, that are the Physical Component Summary (PCS) and the Mental
      Component Summary (MCS); Cronbach's alpha for PCS-12 and MCS-12 was 0.73 and
      0.72, respectively. Known-groups comparison showed that the SF-12 discriminated
      well between men and women and those who differed in age and educational status
      (P < 0.001). In addition, correlations between the SF-12 scales and single items
      showed that the physical functioning, role physical, bodily pain and general
      health subscales correlated higher with the PCS-12 score, while the vitality,
      social functioning, role emotional and mental health subscales more correlated
      with the MCS-12 score lending support to its good convergent validity. Finally
      the principal component analysis indicated a two-factor structure (physical and
      mental health) that jointly accounted for 57.8% of the variance. The confirmatory
      factory analysis also indicated a good fit to the data for the two-latent
      structure (physical and mental health). CONCLUSION: In general the findings
      suggest that the SF-12 is a reliable and valid measure of health related quality
      of life among Iranian population. However, further studies are needed to
      establish stronger psychometric properties for this alternative form of the SF-36
      Health Survey in Iran.

PMID- 19758428
TI  - Prevention of type 2 diabetes in adults with impaired glucose tolerance: the
      European Diabetes Prevention RCT in Newcastle upon Tyne, UK.
AB  - BACKGROUND: Diabetes prevalence is increasing. The Finnish Diabetes Prevention
      Study (DPS) showed a 58% reduction in Type 2 Diabetes (T2D) incidence in adults
      with impaired glucose tolerance (IGT). The European Diabetes Prevention Study
      (EDIPS) extends the DPS to different European populations, using the same study
      design. In the Newcastle arm of this study (EDIPS-Newcastle), we tested the
      hypothesis that T2D can be prevented by lifestyle intervention and explored
      secondary outcomes in relation to diabetes incidence. METHODS: We recruited 102
      participants (42 men and 60 women, mean age 57 years, mean BMI 34 kgm-2) with IGT
      to EDIPS-Newcastle and randomised to Intervention and usual care Control groups.
      The intervention included individual motivational interviewing aimed at: weight
      reduction, increase in physical activity, fibre and carbohydrate intake and
      reduction of fat intake (secondary outcomes). The primary outcome was diagnosis
      of T2D. RESULTS: Mean duration of follow-up was 3.1 years. T2D was diagnosed in
      16 participants (I = 5, C = 11). Absolute incidence of T2D was 32.7 per 1000
      person-years in the Intervention-group and 67.1 per 1000 person-years in the
      Control-group. The overall incidence of diabetes was reduced by 55% in the
      Intervention-group, compared with the Control-group: RR 0.45 (95%CI 0.2 to
      1.2).Explanatory survival analysis of secondary outcomes showed that those who
      sustained beneficial changes for two or more years reduced their risk of
      developing T2D. CONCLUSION: Our results are consistent with other diabetes
      prevention trials. This study was designed as part of a larger study and although
      the sample size limits statistical significance, the results contribute to the
      evidence that T2D can be prevented by lifestyle changes in adults with IGT. In
      explanatory analysis small sustained beneficial changes in weight, physical
      activity or dietary factors were associated with reduction in T2D incidence.
      TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number
      registry (ISRCTN) Registry number: ISRCTN15670600. (http://www.controlled
      trials.com/isrctn/search.html?srch=15670600&sort=3&dir=desc&max=10).

PMID- 19758429
TI  - Risk factors for operated carpal tunnel syndrome: a multicenter population-based
      case-control study.
AB  - BACKGROUND: Carpal tunnel syndrome (CTS) is a socially and economically relevant
      disease caused by compression or entrapment of the median nerve within the carpal
      tunnel. This population-based case-control study aims to investigate
      occupational/non-occupational risk factors for surgically treated CTS. METHODS:
      Cases (n = 220) aged 18-65 years were randomly drawn from 13 administrative
      databases of citizens who were surgically treated with carpal tunnel release
      during 2001. Controls (n = 356) were randomly sampled from National Health
      Service registry records and were frequency matched by age-gender-specific CTS
      hospitalization rates. RESULTS: At multivariate analysis, risk factors were blue
      collar/housewife status, BMI > or = 30 kg/m2, sibling history of CTS and
      coexistence of trigger finger. Being relatively tall (cut-offs based on tertiles:
      women > or =165 cm; men > or =175 cm) was associated with lower risk. Blue-collar
      work was a moderate/strong risk factor in both sexes. Raised risks were apparent
      for combinations of biomechanical risk factors that included frequent
      repetitivity and sustained force. CONCLUSION: This study strongly underlines the
      relevance of biomechanical exposures in both non-industrial and industrial work
      as risk factors for surgically treated CTS.

PMID- 19758430
TI  - Heterologous oligonucleotide microarrays for transcriptomics in a non-model
      species; a proof-of-concept study of drought stress in Musa.
AB  - BACKGROUND: 'Systems-wide' approaches such as microarray RNA-profiling are
      ideally suited to the study of the complex overlapping responses of plants to
      biotic and abiotic stresses. However, commercial microarrays are only available
      for a limited number of plant species and development costs are so substantial as
      to be prohibitive for most research groups. Here we evaluate the use of cross
      hybridisation to Affymetrix oligonucleotide GeneChip(R) microarrays to profile
      the response of the banana (Musa spp.) leaf transcriptome to drought stress using
      a genomic DNA (gDNA)-based probe-selection strategy to improve the efficiency of
      detection of differentially expressed Musa transcripts. RESULTS: Following cross
      hybridisation of Musa gDNA to the Rice GeneChip(R) Genome Array, ~33,700 gene
      specific probe-sets had a sufficiently high degree of homology to be retained for
      transcriptomic analyses. In a proof-of-concept approach, pooled RNA representing
      a single biological replicate of control and drought stressed leaves of the Musa
      cultivar 'Cachaco' were hybridised to the Affymetrix Rice Genome Array. A total
      of 2,910 Musa gene homologues with a >2-fold difference in expression levels were
      subsequently identified. These drought-responsive transcripts included many
      functional classes associated with plant biotic and abiotic stress responses, as
      well as a range of regulatory genes known to be involved in coordinating abiotic
      stress responses. This latter group included members of the ERF, DREB, MYB, bZIP
      and bHLH transcription factor families. Fifty-two of these drought-sensitive Musa
      transcripts were homologous to genes underlying QTLs for drought and cold
      tolerance in rice, including in 2 instances QTLs associated with a single
      underlying gene. The list of drought-responsive transcripts also included genes
      identified in publicly-available comparative transcriptomics experiments.
      CONCLUSION: Our results demonstrate that despite the general paucity of
      nucleotide sequence data in Musa and only distant phylogenetic relations to rice,
      gDNA probe-based cross-hybridisation to the Rice GeneChip(R) is a highly
      promising strategy to study complex biological responses and illustrates the
      potential of such strategies for gene discovery in non-model species.

PMID- 19758431
TI  - Automated seeding of specialised wiki knowledgebases with BioKb.
AB  - BACKGROUND: Wiki technology has become a ubiquitous mechanism for dissemination
      of information, and places strong emphasis on collaboration. We aimed to leverage
      wiki technology to allow small groups of researchers to collaborate around a
      specific domain, for example a biological pathway. Automatically gathered seed
      data could be modified by the group and enriched with domain specific
      information. RESULTS: We describe a software system, BioKb, implemented as a
      plugin for the TWiki engine, and designed to facilitate construction of a field
      specific wiki containing collaborative and automatically generated content.
      Features of this system include: query of publicly available resources such as
      KEGG, iHOP and MeSH, to generate 'seed' content for topics; simple definition of
      structure for topics of different types via an administration page; and
      interactive incorporation of relevant PubMed references. An exemplar is shown for
      the use of this system, in the creation of the RAASWiki knowledgebase on the
      renin-angiotensin-aldosterone system (RAAS). RAASWiki has been seeded with data
      by use of BioKb, and will be the subject of ongoing development into an extensive
      knowledgebase on the RAAS. CONCLUSION: The BioKb system is available from
      http://www.bioinf.mvm.ed.ac.uk/twiki/bin/view/TWiki/BioKbPlugin as a plugin for
      the TWiki engine.

PMID- 19758432
TI  - Gene networks in Drosophila melanogaster: integrating experimental data to
      predict gene function.
AB  - BACKGROUND: Discovering the functions of all genes is a central goal of
      contemporary biomedical research. Despite considerable effort, we are still far
      from achieving this goal in any metazoan organism. Collectively, the growing body
      of high-throughput functional genomics data provides evidence of gene function,
      but remains difficult to interpret. RESULTS: We constructed the first network of
      functional relationships for Drosophila melanogaster by integrating most of the
      available, comprehensive sets of genetic interaction, protein-protein
      interaction, and microarray expression data. The complete integrated network
      covers 85% of the currently known genes, which we refined to a high confidence
      network that includes 20,000 functional relationships among 5,021 genes. An
      analysis of the network revealed a remarkable concordance with prior knowledge.
      Using the network, we were able to infer a set of high-confidence Gene Ontology
      biological process annotations on 483 of the roughly 5,000 previously unannotated
      genes. We also show that this approach is a means of inferring annotations on a
      class of genes that cannot be annotated based solely on sequence similarity.
      Lastly, we demonstrate the utility of the network through reanalyzing gene
      expression data to both discover clusters of coregulated genes and compile a list
      of candidate genes related to specific biological processes. CONCLUSIONS: Here we
      present the the first genome-wide functional gene network in D. melanogaster. The
      network enables the exploration, mining, and reanalysis of experimental data, as
      well as the interpretation of new data. The inferred annotations provide testable
      hypotheses of previously uncharacterized genes.

PMID- 19758433
TI  - Matrix metalloproteinases in subjects with type 1 diabetes.
AB  - BACKGROUND: Nephropathy is serious complication of diabetes. We have previously
      shown that level of the proteoglycan syndecan-1 in blood is associated with
      ultrastructural kidney changes in young persons with type 1 diabetes.
      Dysregulation of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix
      metalloproteinases (TIMPs) may contribute to the development of nephropathy. The
      aim of this study was to investigate if the levels of MMPs in blood samples are
      potential markers of early nephropathy in type 1 diabetes. METHODS: Blood samples
      were collected from type 1 diabetes patients after 11 years of diabetes (n = 15)
      and healthy volunteers (n = 12) and stored at /80 degrees C until measurement.
      Levels and activities of serum MMP-2, MMP-9, TIMP-1 and TIMP- 2 were analyzed and
      compared to those of control individuals using ELISA, SDS-PAGE gelatin
      zymography, and Western blot analysis. RESULTS: The serum levels of both MMP-9
      and MMP-2 were significantly higher in subjects with type 1 diabetes, compared to
      controls (p = 0.016 and p = 0.008 respectively). Western blotting revealed no
      differences between the two groups in the levels of TIMP-1 or TIMP-2,
      respectively. CONCLUSION: Our MMP analysis of serum from a limited number of
      patients with type 1 diabetes suggest that such analysis is potentially useful as
      markers in studies of people at risk of progression to chronic kidney disease.

PMID- 19758434
TI  - Protective effect of geranylgeranylacetone, an inducer of heat shock protein 70,
      against drug-induced lung injury/fibrosis in an animal model.
AB  - BACKGROUND: To determine whether oral administration of geranylgeranylacetone
      (GGA), a nontoxic anti-ulcer drug that is an inducer of heat shock protein (HSP)
      70, protects against drug-induced lung injury/fibrosis in vivo. METHODS: We used
      a bleomycin (BLM)-induced lung fibrosis model in which mice were treated with
      oral 600 mg/kg of GGA before and after BLM administration. Inflammation and
      fibrosis were evaluated by histological scoring, hydroxyproline content in the
      lung and inflammatory cell count, and quantification by ELISA of macrophage
      inflammatory protein-2 (MIP-2) in bronchoalveolar lavage fluid. Apoptosis was
      evaluated by the TUNEL method. The induction of HSP70 in the lung was examined
      with western blot analysis and its localization was determined by
      immunohistochemistry. RESULTS: We confirmed the presence of inflammation and
      fibrosis in the BLM-induced lung injury model and induction of HSP70 by oral
      administration of GGA. GGA prevented apoptosis of cellular constituents of lung
      tissue, such as epithelial cells, most likely related to the de novo induction of
      HSP70 in the lungs. GGA-treated mice also showed less fibrosis of the lungs,
      associated with the findings of suppression of both production of MIP-2 and
      inflammatory cell accumulation in the injured lung, compared with vehicle-treated
      mice. CONCLUSION: GGA had a protective effect on drug-induced lung
      injury/fibrosis. Disease-modifying antirheumatic drugs such as methotrexate,
      which are indispensable for the treatment of rheumatoid arthritis, often cause
      interstitial lung diseases, an adverse event that currently cannot be prevented.
      Clinical use of GGA for drug-induced pulmonary fibrosis might be considered in
      the future.

PMID- 19758435
TI  - Effects of typical and atypical antipsychotic drugs on gene expression profiles
      in the liver of schizophrenia subjects.
AB  - BACKGROUND: Although much progress has been made on antipsychotic drug
      development, precise mechanisms behind the action of typical and atypical
      antipsychotics are poorly understood. METHODS: We performed genome-wide
      expression profiling to study effects of typical antipsychotics and atypical
      antipsychotics in the postmortem liver of schizophrenia patients using
      microarrays (Affymetrix U133 plus2.0). We classified the subjects into typical
      antipsychotics (n = 24) or atypical antipsychotics (n = 26) based on their
      medication history, and compared gene expression profiles with unaffected
      controls (n = 34). We further analyzed individual antipsychotic effects on gene
      expression by sub-classifying the subjects into four major antipsychotic groups
      including haloperidol, phenothiazines, olanzapine and risperidone. RESULTS:
      Typical antipsychotics affected genes associated with nuclear protein, stress
      responses and phosphorylation, whereas atypical antipsychotics affected genes
      associated with golgi/endoplasmic reticulum and cytoplasm transport. Comparison
      between typical antipsychotics and atypical antipsychotics further identified
      genes associated with lipid metabolism and mitochondrial function. Analyses on
      individual antipsychotics revealed a set of genes (151 transcripts, FDR adjusted
      p < 0.05) that are differentially regulated by four antipsychotics, particularly
      by phenothiazines, in the liver of schizophrenia patients. CONCLUSION: Typical
      antipsychotics and atypical antipsychotics affect different genes and biological
      function in the liver. Typical antipsychotic phenothiazines exert robust effects
      on gene expression in the liver that may lead to liver toxicity. The genes found
      in the current study may benefit antipsychotic drug development with better
      therapeutic and side effect profiles.

PMID- 19758436
TI  - Pepsin homologues in bacteria.
AB  - BACKGROUND: Peptidase family A1, to which pepsin belongs, had been assumed to be
      restricted to eukaryotes. The tertiary structure of pepsin shows two lobes with
      similar folds and it has been suggested that the gene has arisen from an ancient
      duplication and fusion event. The only sequence similarity between the lobes is
      restricted to the motif around the active site aspartate and a hydrophobic
      hydrophobic-Gly motif. Together, these contribute to an essential structural
      feature known as a psi-loop. There is one such psi-loop in each lobe, and so each
      lobe presents an active Asp. The human immunodeficiency virus peptidase,
      retropepsin, from peptidase family A2 also has a similar fold but consists of one
      lobe only and has to dimerize to be active. All known members of family A1 show
      the bilobed structure, but it is unclear if the ancestor of family A1 was similar
      to an A2 peptidase, or if the ancestral retropepsin was derived from a half
      pepsin gene. The presence of a pepsin homologue in a prokaryote might give
      insights into the evolution of the pepsin family. RESULTS: Homologues of the
      aspartic peptidase pepsin have been found in the completed genomic sequences from
      seven species of bacteria. The bacterial homologues, unlike those from
      eukaryotes, do not possess signal peptides, and would therefore be intracellular
      acting at neutral pH. The bacterial homologues have Thr218 replaced by Asp, a
      change which in renin has been shown to confer activity at neutral pH. No pepsin
      homologues could be detected in any archaean genome. CONCLUSION: The peptidase
      family A1 is found in some species of bacteria as well as eukaryotes. The
      bacterial homologues fall into two groups, one from oceanic bacteria and one from
      plant symbionts. The bacterial homologues are all predicted to be intracellular
      proteins, unlike the eukaryotic enzymes. The bacterial homologues are bilobed
      like pepsin, implying that if no horizontal gene transfer has occurred the
      duplication and fusion event might be very ancient indeed, preceding the
      divergence of bacteria and eukaryotes. It is unclear whether all the bacterial
      homologues are derived from horizontal gene transfer, but those from the plant
      symbionts probably are. The homologues from oceanic bacteria are most closely
      related to memapsins (or BACE-1 and BACE-2), but are so divergent that they are
      close to the root of the phylogenetic tree and to the division of the A1 family
      into two subfamilies.

PMID- 19758437
TI  - Evaluation of molecular descriptors for antitumor drugs with respect to
      noncovalent binding to DNA and antiproliferative activity.
AB  - BACKGROUND: Small molecules that bind reversibly to DNA are among the antitumor
      drugs currently used in chemotherapy. In the pursuit of a more rational approach
      to cancer chemotherapy based upon these molecules, it is necessary to exploit the
      interdependency between DNA-binding affinity, sequence selectivity and
      cytotoxicity. For drugs binding noncovalently to DNA, it is worth exploring
      whether molecular descriptors, such as their molecular weight or the number of
      potential hydrogen acceptors/donors, can account for their DNA-binding affinity
      and cytotoxicity. RESULTS: Fifteen antitumor agents, which are in clinical use or
      being evaluated as part of the National Cancer Institute's drug screening effort,
      were analyzed in silico to assess the contribution of various molecular
      descriptors to their DNA-binding affinity, and the capacity of the descriptors
      and DNA-binding constants for predicting cell cytotoxicity. Equations to predict
      drug-DNA binding constants and growth-inhibitory concentrations were obtained by
      multiple regression following rigorous statistical procedures. CONCLUSION: For
      drugs binding reversibly to DNA, both their strength of binding and their
      cytoxicity are fairly predicted from molecular descriptors by using multiple
      regression methods. The equations derived may be useful for rational drug design.
      The results obtained agree with that compounds more active across the National
      Cancer Institute's 60-cell line data set tend to have common structural features.

PMID- 19758438
TI  - Transcription factor AP-1 in esophageal squamous cell carcinoma: alterations in
      activity and expression during human Papillomavirus infection.
AB  - BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a leading cause of
      cancer-related deaths in Jammu and Kashmir (J&K) region of India. A substantial
      proportion of esophageal carcinoma is associated with infection of high-risk HPV
      type 16 and HPV18, the oncogenic expression of which is controlled by host cell
      transcription factor Activator Protein-1 (AP-1). We, therefore, have investigated
      the role of DNA binding and expression pattern of AP-1 in esophageal cancer with
      or without HPV infection. METHODS: Seventy five histopathologically-confirmed
      esophageal cancer and an equal number of corresponding adjacent normal tissue
      biopsies from Kashmir were analyzed for HPV infection, DNA binding activity and
      expression of AP-1 family of proteins by PCR, gel shift assay and immunoblotting
      respectively. RESULTS: A high DNA binding activity and elevated expression of AP
      1 proteins were observed in esophageal cancer, which differed between HPV
      positive (19%) and HPV negative (81%) carcinomas. While JunB, c-Fos and Fra-1
      were the major contributors to AP-1 binding activity in HPV negative cases, Fra-1
      was completely absent in HPV16 positive cancers. Comparison of AP-1 family
      proteins demonstrated high expression of JunD and c-Fos in HPV positive tumors,
      but interestingly, Fra-1 expression was extremely low or nil in these tumor
      tissues. CONCLUSION: Differential AP-1 binding activity and expression of its
      specific proteins between HPV--positive and HPV--negative cases indicate that AP
      1 may play an important role during HPV-induced esophageal carcinogenesis.

PMID- 19758439
TI  - Using the pea aphid Acrythociphon pisum as a tool for screening biological
      responses to chemicals and drugs.
AB  - BACKGROUND: Though the biological process of aphid feeding is well documented, no
      one to date has sought to apply it as a tool to screen the biological responses
      to chemicals and drugs, in ecotoxicology, genotoxicology and/or for interactions
      in the cascade of sequential molecular events of embryogenesis. Parthenogenetic
      insect species present the advantage of an anatomical system composed of multiple
      germarium/ovarioles in the same mother with all the intermediate maturation
      stages of embryos from oocyte to first instar larva birth. This could be used as
      an interesting model to visualize at which step drugs interact with the cell
      signalling pathway during the ordered developmental process. FINDINGS: We
      designed a simple test for screening drugs by investigating simultaneously zygote
      mitotic division, the progression of embryo development, cell differentiation at
      early developmental stages and finally organogenesis and population growth rate.
      We aimed to analyze the toxicology effects of compounds and/or their interference
      on cellular signalling by examining at which step of the cascade, from zygote to
      mature embryo, the developmental process is perturbed. We reasoned that a
      parthenogenetic founder insect, in which the ovarioles shelter numerous embryos
      at different developmental stages, would allow us to precisely pinpoint the step
      of embryogenesis in which chemicals act through specific molecular targets as the
      known ordered homeobox genes. CONCLUSION: Using this method we report the results
      of a genotoxicological and demographic analysis of three compound models bearing
      in common a bromo group: one is integrated as a base analog in DNA synthesis, two
      others activate permanently kinases. We report that one compound (Br-du) altered
      drastically embryogenesis, which argues in favor of this simple technique as a
      cheap first screening of chemicals or drugs to be used in a number of
      genotoxicology applications.

PMID- 19758440
TI  - Identification of biology-based breast cancer types with distinct predictive and
      prognostic features: role of steroid hormone and HER2 receptor expression in
      patients treated with neoadjuvant anthracycline/taxane-based chemotherapy.
AB  - INTRODUCTION: Reliable predictive and prognostic markers for routine diagnostic
      purposes are needed for breast cancer patients treated with neoadjuvant
      chemotherapy. We evaluated protein biomarkers in a cohort of 116 participants of
      the GeparDuo study on anthracycline/taxane-based neoadjuvant chemotherapy for
      operable breast cancer to test for associations with pathological complete
      response (pCR) and disease-free survival (DFS). Particularly, we evaluated if
      interactions between hormone receptor (HR) and human epidermal growth factor
      receptor 2 (HER2) expression might lead to a different clinical behavior of
      HR+/HER2+ co-expressing and HR+/HER2- tumors and whether subgroups of triple
      negative tumors might be identified by the help of Ki67 labeling index,
      cytokeratin 5/6 (CK5/6), as well as cyclooxygenase-2 (COX-2), and Y-box binding
      protein 1 (YB-1) expression. METHODS: Expression analysis was performed using
      immunohistochemistry and silver-enhanced in situ hybridization on tissue
      microarrays (TMAs) of pretherapeutic core biopsies. RESULTS: pCR rates were
      significantly different between the biology-based tumor types (P = 0.044) with
      HR+/HER2+ and HR-/HER2- tumors having higher pCR rates than HR+/HER2- tumors.
      Ki67 labeling index, confirmed as significant predictor of pCR in the whole
      cohort (P = 0.001), identified HR-/HER- (triple negative) carcinomas with a
      higher chance for a pCR (P = 0.006). Biology-based tumor type (P = 0.046 for
      HR+/HER2+ vs. HR+/HER2-), Ki67 labeling index (P = 0.028), and treatment arm (P =
      0.036) were independent predictors of pCR in a multivariate model. DFS was
      different in the biology-based tumor types (P < 0.0001) with HR+/HER2- and
      HR+/HER2+ tumors having the best prognosis and HR-/HER2+ tumors showing the worst
      outcome. Biology-based tumor type was an independent prognostic factor for DFS in
      multivariate analysis (P < 0.001). CONCLUSIONS: Our data demonstrate that a
      biology-based breast cancer classification using estrogen receptor (ER),
      progesterone receptor (PgR), and HER2 bears independent predictive and prognostic
      potential. The HR+/HER2+ co-expressing carcinomas emerged as a group of tumors
      with a good response rate to neoadjuvant chemotherapy and a favorable prognosis.
      HR+/HER2- tumors had a good prognosis irrespective of a pCR, whereas patients
      with HR-/HER- and HR-/HER+ tumors, especially if they had not achieved a pCR, had
      an unfavorable prognosis and are in need of additional treatment options.

PMID- 19758441
TI  - Dissecting the fission yeast regulatory network reveals phase-specific control
      elements of its cell cycle.
AB  - BACKGROUND: Fission yeast Schizosaccharomyces pombe and budding yeast
      Saccharomyces cerevisiae are among the original model organisms in the study of
      the cell-division cycle. Unlike budding yeast, no large-scale regulatory network
      has been constructed for fission yeast. It has only been partially characterized.
      As a result, important regulatory cascades in budding yeast have no known or
      complete counterpart in fission yeast. RESULTS: By integrating genome-wide data
      from multiple time course cell cycle microarray experiments we reconstructed a
      gene regulatory network. Based on the network, we discovered in addition to
      previously known regulatory hubs in M phase, a new putative regulatory hub in the
      form of the HMG box transcription factor SPBC19G7.04. Further, we inferred
      periodic activities of several less known transcription factors over the course
      of the cell cycle, identified over 500 putative regulatory targets and detected
      many new phase-specific and conserved cis-regulatory motifs. In particular, we
      show that SPBC19G7.04 has highly significant periodic activity that peaks in
      early M phase, which is coordinated with the late G2 activity of the forkhead
      transcription factor fkh2. Finally, using an enhanced Bayesian algorithm to co
      cluster the expression data, we obtained 31 clusters of co-regulated genes 1)
      which constitute regulatory modules from different phases of the cell cycle, 2)
      whose phase order is coherent across the 10 time course experiments, and 3) which
      lead to identification of phase-specific control elements at both the
      transcriptional and post-transcriptional levels in S. pombe. In particular, the
      ribosome biogenesis clusters expressed in G2 phase reveal new, highly conserved
      RNA motifs. CONCLUSION: Using a systems-level analysis of the phase-specific
      nature of the S. pombe cell cycle gene regulation, we have provided new testable
      evidence for post-transcriptional regulation in the G2 phase of the fission yeast
      cell cycle. Based on this comprehensive gene regulatory network, we demonstrated
      how one can generate and investigate plausible hypotheses on fission yeast cell
      cycle regulation which can potentially be explored experimentally.

PMID- 19758443
TI  - E box motifs as mediators of proviral latency of human retroviruses.
AB  - The palindromic sequence motifs (CANNTG) known as E boxes are considered as
      binding sites for the basic helix-loop-helix (bHLH) class of DNA-binding
      proteins. Their presence has been reported in the long terminal repeats (LTR) of
      the HIV-1 and HTLV-1 proviruses. Their close proximity with the TATA region of
      both LTRs indicates that the bHLH proteins may act as important regulators of the
      function of proviral transcription. Indeed, observations on HIV-1 and recent
      results on HTLV-1 underline that these E boxes may be critically involved in the
      regulation of the proviral transcription of these human retroviruses. Indeed, of
      the two E boxes flanking the TATA sequences of the HIV-1 provirus, the 3' E box
      has been implicated in the transcriptional inhibition of viral gene expression.
      Such a role might also be played by the unique 5' E box present in the HTLV-1
      LTR. In both cases, the expression of tissue-specfic bHLH proteins, like TAL1
      might counteract the inhibitory effect exerted by E box proteins, thereby
      increasing proviral transcription. Finally, a phylogenetic study encompassing
      several subtypes of these two human retroviruses underlines that these E box
      motifs have recently appeared in the proviral LTRs and may be considered as
      potential mediators in the establishment of proviral latency.

PMID- 19758442
TI  - Human cellular restriction factors that target HIV-1 replication.
AB  - Recent findings have highlighted roles played by innate cellular factors in
      restricting intracellular viral replication. In this review, we discuss in brief
      the activities of apolipoprotein B mRNA-editing enzyme 3G (APOBEC3G), bone marrow
      stromal cell antigen 2 (BST-2), cyclophilin A, tripartite motif protein 5 alpha
      (Trim5alpha), and cellular microRNAs as examples of host restriction factors that
      target HIV-1. We point to countermeasures encoded by HIV-1 for moderating the
      potency of these cellular restriction functions.

PMID- 19758444
TI  - HIV/AIDS, growth and poverty in KwaZulu-Natal and South Africa: an integrated
      survey, demographic and economy-wide analysis.
AB  - BACKGROUND: This paper estimates the economic impact of HIV/AIDS on the KwaZulu
      Natal province and the rest of South Africa. METHODS: We extended previous
      studies by employing: an integrated analytical framework that combined firm
      surveys of workers' HIV prevalence by sector and occupation; a demographic model
      that produced both population and workforce projections; and a regionalized
      economy-wide model linked to a survey-based micro-simulation module. This
      framework permits a full macro-microeconomic assessment. RESULTS: Results
      indicate that HIV/AIDS greatly reduces annual economic growth, mainly by lowering
      the long-run rate of technical change. However, impacts on income poverty are
      small, and inequality is reduced by HIV/AIDS. This is because high unemployment
      among low-income households minimises the economic costs of increased mortality.
      By contrast, slower economic growth hurts higher income households despite lower
      HIV prevalence. CONCLUSION: We conclude that the increase in economic growth that
      results from addressing HIV/AIDS is sufficient to offset the population pressure
      placed on income poverty. Moreover, incentives to mitigate HIV/AIDS lie not only
      with poorer infected households, but also with uninfected higher income
      households.Our findings reveal the substantial burden that HIV/AIDS places on
      future economic development in KwaZulu-Natal and South Africa, and confirms the
      need for policies to curb the economic costs of the pandemic.

PMID- 19758445
TI  - An unexpectedly long history of sexual selection in birds-of-paradise.
AB  - BACKGROUND: The birds-of-paradise (Paradisaeidae) form one of the most prominent
      avian examples of sexual selection and show a complex biogeographical
      distribution. The family has accordingly been used as a case-study in several
      significant evolutionary and biogeographical syntheses. As a robust phylogeny of
      the birds-of-paradise has been lacking, these hypotheses have been tentative and
      difficult to assess. Here we present a well supported species phylogeny with
      divergence time estimates of the birds-of-paradise. We use this to assess if the
      rates of the evolution of sexually selected traits and speciation have been
      excessively high within the birds-of-paradise, as well as to re-interpret
      biogeographical patterns in the group. RESULTS: The phylogenetic results confirm
      some traditionally recognized relationships but also suggest novel ones.
      Furthermore, we find that species pairs are geographically more closely linked
      than previously assumed. The divergence time estimates suggest that speciation
      within the birds-of-paradise mainly took place during the Miocene and the
      Pliocene, and that several polygynous and morphologically homogeneous genera are
      several million years old. Diversification rates further suggest that the
      speciation rate within birds-of-paradise is comparable to that of the enitre core
      Corvoidea. CONCLUSION: The estimated ages of morphologically homogeneous and
      polygynous genera within the birds-of-paradise suggest that there is no need to
      postulate a particularly rapid evolution of sexually selected morphological
      traits. The calculated divergence rates further suggest that the speciation rate
      in birds-of-paradise has not been excessively high. Thus the idea that sexual
      selection could generate high speciation rates and rapid changes in sexual
      ornamentations is not supported by our birds-of-paradise data. Potentially,
      hybridization and long generation times in polygynous male birds-of-paradise have
      constrained morphological diversification and speciation, but external ecological
      factors on New Guinea may also have allowed the birds-of-paradise to develop and
      maintain magnificent male plumages. We further propose that the restricted but
      geographically complex distributions of birds-of-paradise species may be a
      consequence of the promiscuous breeding system.

PMID- 19758447
TI  - The importance of individualized article-specific metrics for evaluating research
      productivity.
AB  - This editorial discusses the rationale for using article-specific rather than
      journal-specific metrics for evaluating highly published authors.

PMID- 19758446
TI  - Lack of efficacy of blueberry in nutritional prevention of azoxymethane-initiated
      cancers of rat small intestine and colon.
AB  - BACKGROUND: Blueberries may lower relative risk for cancers of the
      gastrointestinal tract. Previous work indicated an inhibitory effect of consumed
      blueberry (BB) on formation of aberrant crypt foci (ACF) in colons of male Fisher
      F344 rats (inbred strain). However, effects of BB on colon tumors and in both
      genders are unknown. METHODS: We examined efficacy of BB in inhibition of
      azoxymethane (AOM)-induced colon ACF and intestine tumors in male and female
      Sprague-Dawley rats (outbred strain). Pregnant rats were fed a diet with or
      without 10% BB powder; progeny were weaned to the same diet as their dam and
      received AOM as young adults. RESULTS: Male and female rats on control diet had
      similar numbers of ACF at 6 weeks after AOM administration. BB increased (P <
      0.05) ACF numbers within the distal colon of female but not male rats. There was
      a significant (P < 0.05) diet by gender interaction with respect to total colon
      ACF number. Colon and duodenum tumor incidences were less in females than males
      at 17 weeks after AOM. BB tended (0.1 > P > 0.05) to reduce overall
      gastrointestinal tract tumor incidence in males, however, tumor incidence in
      females was unaffected (P > 0.1) by BB. There was a tendency (0.1 > P > 0.05) for
      fewer adenocarcinomas (relative to total of adenomatous polyps plus
      adenocarcinomas) in colons of female than male tumor-bearing rats; in small
      intestine, this gender difference was significant (P < 0.05). BB favored (P <
      0.05) fewer adenocarcinomas and more adenomatous polyps (as a proportion of total
      tumor number) in female rat small intestine. CONCLUSION: Results did not indicate
      robust cancer-preventive effects of BB. Blueberry influenced ACF occurrence in
      distal colon and tumor progression in duodenum, in gender-specific fashion. Data
      indicate the potential for slowing tumor progression (adenomatous polyp to
      adenocarcinoma) by BB.

PMID- 19758448
TI  - A first principles approach to differential expression in microarray data
      analysis.
AB  - BACKGROUND: The disparate results from the methods commonly used to determine
      differential expression in Affymetrix microarray experiments may well result from
      the wide variety of probe set and probe level models employed. Here we take the
      approach of making the fewest assumptions about the structure of the microarray
      data. Specifically, we only require that, under the null hypothesis that a gene
      is not differentially expressed for specified conditions, for any probe position
      in the gene's probe set: a) the probe amplitudes are independent and identically
      distributed over the conditions, and b) the distributions of the replicated probe
      amplitudes are amenable to classical analysis of variance (ANOVA). Log-amplitudes
      that have been standardized within-chip meet these conditions well enough for our
      approach, which is to perform ANOVA across conditions for each probe position,
      and then take the median of the resulting (1 - p) values as a gene-level measure
      of differential expression. RESULTS: We applied the technique to the HGU-133A, HG
      U95A, and "Golden Spike" spike-in data sets. The resulting receiver operating
      characteristic (ROC) curves compared favorably with other published results. This
      procedure is quite sensitive, so much so that it has revealed the presence of
      probe sets that might properly be called "unanticipated positives" rather than
      "false positives", because plots of these probe sets strongly suggest that they
      are differentially expressed. CONCLUSION: The median ANOVA (1-p) approach
      presented here is a very simple methodology that does not depend on any specific
      probe level or probe models, and does not require any pre-processing other than
      within-chip standardization of probe level log amplitudes. Its performance is
      comparable to other published methods on the standard spike-in data sets, and has
      revealed the presence of new categories of probe sets that might properly be
      referred to as "unanticipated positives" and "unanticipated negatives" that need
      to be taken into account when using spiked-in data sets at "truthed" test beds.

PMID- 19758449
TI  - Educating the power: HIV/AIDS and parliamentarians of Pakistan.
AB  - Increasing rates of HIV have been recorded amongst the Injection Drug User
      community from all parts of Pakistan. This has mobilized the health authorities
      into definitive action before there is a general spread of the epidemic into the
      Pakistani populace. Lacking any formal research as pertains to HIV policy
      development in Pakistan, international collaborating agencies, including the
      United Nations, are aiding in the formulation of a national policy to tackle
      HIV/AIDS. This article discusses the progress and importance of interventions
      being conducted amongst the Parliamentarians of Pakistan, relatively unchartered
      waters. The series of Seminars help to appraise the Parliamentarians of the
      ground situation as pertains to HIV in their constituencies, aiming to ultimately
      generate federal and provincial governmental policies, and a solid strategy to
      combat the spread of HIV/AIDS in Pakistan.

PMID- 19758450
TI  - High-level chromate resistance in Arthrobacter sp. strain FB24 requires
      previously uncharacterized accessory genes.
AB  - BACKGROUND: The genome of Arthrobacter sp. strain FB24 contains a chromate
      resistance determinant (CRD), consisting of a cluster of 8 genes located on a
      10.6 kb fragment of a 96 kb plasmid. The CRD includes chrA, which encodes a
      putative chromate efflux protein, and three genes with amino acid similarities to
      the amino and carboxy termini of ChrB, a putative regulatory protein. There are
      also three novel genes that have not been previously associated with chromate
      resistance in other bacteria; they encode an oxidoreductase (most similar to
      malate:quinone oxidoreductase), a functionally unknown protein with a WD40 repeat
      domain and a lipoprotein. To delineate the contribution of the CRD genes to the
      FB24 chromate [Cr(VI)] response, we evaluated the growth of mutant strains
      bearing regions of the CRD and transcript expression levels in response to Cr(VI)
      challenge. RESULTS: A chromate-sensitive mutant (strain D11) was generated by
      curing FB24 of its 96-kb plasmid. Elemental analysis indicated that chromate
      exposed cells of strain D11 accumulated three times more chromium than strain
      FB24. Introduction of the CRD into strain D11 conferred chromate resistance
      comparable to wild-type levels, whereas deletion of specific regions of the CRD
      led to decreased resistance. Using real-time reverse transcriptase PCR, we show
      that expression of each gene within the CRD is specifically induced in response
      to chromate but not by lead, hydrogen peroxide or arsenate. Higher levels of chrA
      expression were achieved when the chrB orthologs and the WD40 repeat domain genes
      were present, suggesting their possible regulatory roles. CONCLUSION: Our
      findings indicate that chromate resistance in Arthrobacter sp. strain FB24 is due
      to chromate efflux through the ChrA transport protein. More importantly, new
      genes have been identified as having significant roles in chromate resistance.
      Collectively, the functional predictions of these additional genes suggest the
      involvement of a signal transduction system in the regulation of chromate efflux
      and warrants further study.

PMID- 19758451
TI  - Efficient oligonucleotide probe selection for pan-genomic tiling arrays.
AB  - BACKGROUND: Array comparative genomic hybridization is a fast and cost-effective
      method for detecting, genotyping, and comparing the genomic sequence of unknown
      bacterial isolates. This method, as with all microarray applications, requires
      adequate coverage of probes targeting the regions of interest. An unbiased tiling
      of probes across the entire length of the genome is the most flexible design
      approach. However, such a whole-genome tiling requires that the genome sequence
      is known in advance. For the accurate analysis of uncharacterized bacteria, an
      array must query a fully representative set of sequences from the species' pan
      genome. Prior microarrays have included only a single strain per array or the
      conserved sequences of gene families. These arrays omit potentially important
      genes and sequence variants from the pan-genome. RESULTS: This paper presents a
      new probe selection algorithm (PanArray) that can tile multiple whole genomes
      using a minimal number of probes. Unlike arrays built on clustered gene families,
      PanArray uses an unbiased, probe-centric approach that does not rely on
      annotations, gene clustering, or multi-alignments. Instead, probes are evenly
      tiled across all sequences of the pan-genome at a consistent level of coverage.
      To minimize the required number of probes, probes conserved across multiple
      strains in the pan-genome are selected first, and additional probes are used only
      where necessary to span polymorphic regions of the genome. The viability of the
      algorithm is demonstrated by array designs for seven different bacterial pan
      genomes and, in particular, the design of a 385,000 probe array that fully tiles
      the genomes of 20 different Listeria monocytogenes strains with overlapping
      probes at greater than twofold coverage. CONCLUSION: PanArray is an
      oligonucleotide probe selection algorithm for tiling multiple genome sequences
      using a minimal number of probes. It is capable of fully tiling all genomes of a
      species on a single microarray chip. These unique pan-genome tiling arrays
      provide maximum flexibility for the analysis of both known and uncharacterized
      strains.

PMID- 19758452
TI  - Low documentation of chronic kidney disease among high-risk patients in a managed
      care population: a retrospective cohort study.
AB  - BACKGROUND: Early detection of chronic kidney disease (CKD) is sub-optimal among
      the general population and among high risk patients. The prevalence and impact of
      major CKD risk factors, diabetes (DM) and hypertension (HTN), on CKD
      documentation among managed care populations have not been previously reported.
      We examined this issue in a Kaiser Permanente Georgia (KPG) CKD cohort. METHODS:
      KPG enrollees were included in the CKD cohort if they had eGFRs between 60 and
      365 days apart that were <90 ml/min during 1999-2006. The current analysis is
      restricted to participants with eGFR 10-59 ml/min/1.73 m2. CKD documentation was
      defined as a presenting diagnosis of CKD by a primary care physician or
      nephrologist using ICD-9 event codes. The association between CKD documentation
      and DM and HTN were assessed with multivariate logistic regression models.
      RESULTS: Of the 50,438 subjects within the overall KPG CKD cohort, 20% (N =
      10,266) were eligible for inclusion in the current analysis. Overall, CKD
      diagnosis documentation was low; only 14.4% of subjects had an event-based CKD
      diagnosis at baseline. Gender and types 2 diabetes interacted on CKD
      documentation. The prevalence of CKD documentation increased with the presence of
      hypertension and/or type 2 diabetes, but type 2 diabetes had a lower effect on
      CKD documentation. In multivariate analysis, significant predictors of CKD
      documentation were eGFR, hypertension, type 2 diabetes, congestive heart failure,
      peripheral artery disease, statin use, age and gender. CKD documentation was
      lower among women than similarly affected men. CONCLUSION: Among patients with an
      eGFR 10-59, documentation of CKD diagnosis by primary and subspecialty providers
      is low within a managed care patient cohort. Gender disparities in CKD
      documentation observed in the general population were also present among KPG CKD
      enrollees.

PMID- 19758453
TI  - High ambient temperature and mortality: a review of epidemiologic studies from
      2001 to 2008.
AB  - BACKGROUND: This review examines recent evidence on mortality from elevated
      ambient temperature for studies published from January 2001 to December 2008.
      METHODS: PubMed was used to search for the following keywords: temperature,
      apparent temperature, heat, heat index, and mortality. The search was limited to
      the English language and epidemiologic studies. Studies that reported mortality
      counts or excess deaths following heat waves were excluded so that the focus
      remained on general ambient temperature and mortality in a variety of locations.
      Studies focusing on cold temperature effects were also excluded. RESULTS: Thirty
      six total studies were presented in three tables: 1) elevated ambient temperature
      and mortality; 2) air pollutants as confounders and/or effect modifiers of the
      elevated ambient temperature and mortality association; and 3) vulnerable
      subgroups of the elevated ambient temperature-mortality association. The evidence
      suggests that particulate matter with less than 10 um in aerodynamic diameter and
      ozone may confound the association, while ozone was an effect modifier in the
      warmer months in some locations. Nonetheless, the independent effect of
      temperature and mortality was withheld. Elevated temperature was associated with
      increased risk for those dying from cardiovascular, respiratory, cerebrovascular,
      and some specific cardiovascular diseases, such as ischemic heart disease,
      congestive heart failure, and myocardial infarction. Vulnerable subgroups also
      included: Black racial/ethnic group, women, those with lower socioeconomic
      status, and several age groups, particularly the elderly over 65 years of age as
      well as infants and young children. CONCLUSION: Many of these outcomes and
      vulnerable subgroups have only been identified in recent studies and varied by
      location and study population. Thus, region-specific policies, especially in
      urban areas, are vital to the mitigation of heat-related deaths.

PMID- 19758454
TI  - Physician career satisfaction within specialties.
AB  - BACKGROUND: Specialty-specific data on career satisfaction may be useful for
      understanding physician workforce trends and for counseling medical students
      about career options. METHODS: We analyzed cross-sectional data from 6,590
      physicians (response rate, 53%) in Round 4 (2004-2005) of the Community Tracking
      Study Physician Survey. The dependent variable ranged from +1 to -1 and measured
      satisfaction and dissatisfaction with career. Forty-two specialties were analyzed
      with survey-adjusted linear regressions RESULTS: After adjusting for physician,
      practice, and community characteristics, the following specialties had
      significantly higher satisfaction levels than family medicine: pediatric
      emergency medicine (regression coefficient = 0.349); geriatric medicine (0.323);
      other pediatric subspecialties (0.270); neonatal/prenatal medicine (0.266);
      internal medicine and pediatrics (combined practice) (0.250); pediatrics (0.250);
      dermatology (0.249);and child and adolescent psychiatry (0.203). The following
      specialties had significantly lower satisfaction levels than family medicine:
      neurological surgery (-0.707); pulmonary critical care medicine (-0.273);
      nephrology (-0.206); and obstetrics and gynecology (-0.188). We also found
      satisfaction was significantly and positively related to income and employment in
      a medical school but negatively associated with more than 50 work-hours per-week,
      being a full-owner of the practice, greater reliance on managed care revenue, and
      uncontrollable lifestyle. We observed no statistically significant gender
      differences and no differences between African-Americans and whites. CONCLUSION:
      Career satisfaction varied across specialties. A number of stakeholders will
      likely be interested in these findings including physicians in specialties that
      rank high and low and students contemplating specialty. Our findings regarding
      "less satisfied" specialties should elicit concern from residency directors and
      policy makers since they appear to be in critical areas of medicine.

PMID- 19758455
TI  - Expression of oestrogen receptors, ERalpha, ERbeta, and ERbeta variants, in
      endometrial cancers and evidence that prostaglandin F may play a role in
      regulating expression of ERalpha.
AB  - BACKGROUND: Endometrial cancer is the most common gynaecological malignancy; risk
      factors include exposure to oestrogens and high body mass index. Expression of
      enzymes involved in biosynthesis of oestrogens and prostaglandins (PG) is often
      higher in endometrial cancers when compared with levels detected in normal
      endometrium. Oestrogens bind one of two receptors (ERalpha and ERbeta) encoded by
      separate genes. The full-length receptors function as ligand-activated
      transcription factors; splice variant isoforms of ERbeta lacking a ligand-binding
      domain have also been described. PGs act in an autocrine or paracrine manner by
      binding to specific G-protein coupled receptors. METHODS: We compared expression
      of ERs, progesterone receptor (PR) and cyclooxygenase-2 (COX-2) in stage 1
      endometrial adenocarcinomas graded as well (G1), moderately (G2) or poorly (G3)
      differentiated (n >or= 10 each group) using qRTPCR, single and double
      immunohistochemistry. We used endometrial adenocarcinoma cell lines to
      investigate the impact of PGF2alpha on expression of ERs and PR. RESULTS: Full
      length ERbeta (ERbeta1) and two ERbeta variants (ERbeta2, ERbeta5) were expressed
      in endometrial cancers regardless of grade and the proteins were immunolocalised
      to the nuclei of cells in both epithelial and stromal compartments.
      Immunoexpression of COX-2 was most intense in cells that were ERalphaneg/low.
      Expression of PR in endometrial adenocarcinoma (Ishikawa) cell lines and tissues
      broadly paralleled that of ERalpha. Treatment of adenocarcinoma cells with
      PGF2alpha reduced expression of ERalpha but had no impact on ERbeta1. Cells
      incubated with PGF2alpha were unable to increase expression of PR mRNA when they
      were incubated with E2. CONCLUSION: We have demonstrated that ERbeta5 protein is
      expressed in stage 1 endometrial adenocarcinomas. Expression of three ERbeta
      variants, including the full-length protein is not grade-dependent and most cells
      in poorly differentiated cancers are ERbetapos/ERalphaneg. We found evidence of a
      link between COX-2, its product PGF2alpha, and expression of ERalpha and PR that
      sheds new light on the cross talk between steroid and PG signalling pathways in
      this disease.

PMID- 19758456
TI  - Comparison of CT and integrated PET-CT based radiation therapy planning in
      patients with malignant pleural mesothelioma.
AB  - BACKGROUND: When combined with adequate tumoricidal doses, accurate target volume
      delineation remains to be the one of the most important predictive factors for
      radiotherapy (RT) success in locally advanced or medically inoperable malignant
      pleural mesothelioma (MPM) patients. Recently, 18-fluorodeoxyglucose positron
      emission tomography (PET) has demonstrated significant improvements in diagnosis
      and accurate staging of MPM. However, role of additional PET data has not been
      studied in RT planning (RTP) of patients with inoperable MPM or in those who
      refuse surgery. Therefore, we planned to compare CT with co-registered PET-CT as
      the basis for delineating target volumes in these patients group. METHODS:
      Retrospectively, the CT and co-registered PET-CT data of 13 patients with
      histologically proven MPM were utilized to delineate target volumes separately.
      For each patient, target volumes (gross tumor volume [GTV], clinical target
      volume [CTV], and planning target volume [PTV]) were defined using the CT and PET
      CT fusion data sets. The PTV was measured in two ways: PTV1 was CTV plus a 1-cm
      margin, and PTV2 was GTV plus a 1-cm margin. We analyzed differences in target
      volumes. RESULTS: In 12 of 13 patients, compared to CT-based delineation, PET-CT
      based delineation resulted in a statistically significant decrease in the mean
      GTV, CTV, PTV1, and PTV2. In these 12 patients, mean GTV decreased by 47.1% +/-
      28.4%, mean CTV decreased by 38.7% +/- 24.7%, mean PTV1 decreased by 31.1% +/-
      23.1%, and mean PTV2 decreased by 40.0% +/- 24.0%. In 4 of 13 patients, hilar
      lymph nodes were identified by PET-CT that was not identified by CT alone,
      changing the nodal status of tumor staging in those patients. CONCLUSION: This
      study demonstrated the usefulness of PET-CT-based target volume delineation in
      patients with MPM. Co-registration of PET and CT information reduces the
      likelihood of geographic misses, and additionally, significant reductions
      observed in target volumes may potentially allow escalation of RT dose beyond
      conventional limits potential clinical benefits in tumor control rates, which
      needs to be tested in future studies.

PMID- 19758457
TI  - Characterization of bovine miRNAs by sequencing and bioinformatics analysis.
AB  - BACKGROUND: MicroRNAs (miRNAs) are a family of approximately 22 nucleotide small
      RNA molecules which regulate gene expression by fully or partially binding to
      their complementary sequences in mRNAs or promoters. A large number of miRNAs and
      their expression patterns have been reported in human, mouse and rat. However,
      miRNAs and their expression patterns in live stock species such as beef cattle
      are not well studied. RESULTS: We constructed and sequenced small-RNA libraries
      to yield a total of 13,541 small-RNA sequences from 11 bovine tissues including
      brain, subcutaneous fat, muscle, liver, kidney, spleen and thymus. In total, 228
      miRNAs including 29 novel miRNA candidates were identified. Of the 199 miRNAs,
      101 have been previously reported as bovine miRNAs and the other 98 are bovine
      orthologs of known miRNAs that have been identified in at least one other
      mammalian species. Of the 29 novel miRNA candidates, 17 appeared at this point in
      time to be bovine specific, while the remaining 12 had evidence of evolutionary
      conservation in other mammalian species. Five miRNAs (miR-23a, -23b, -99a, -125b
      and -126-5p) were very abundant across the 11 tissues, accounting for 44.3% of
      all small RNA sequences. The expression analysis of selected miRNAs using qRT-PCR
      also showed that miR-26a and -99a were highly expressed in all tissues, while miR
      122 and miR-133a were predominantly expressed in liver and muscle, respectively.
      CONCLUSION: The miRNA expression patterns among 11 tissues from beef cattle
      revealed that most miRNAs were ubiquitously expressed in all tissues, while only
      a few miRNAs were tissue specific. Only 60% miRNAs in this study were found to
      display strand bias, suggesting that there are some key factors for mature miRNA
      selection other than internal stability. Most bovine miRNAs are highly conserved
      in other three mammalian species, indicating that these miRNAs may have a role in
      different species that are potential molecular markers for evolution.

PMID- 19758458
TI  - Factors affecting the outcome of human blastocyst vitrification.
AB  - With single blastocyst transfer practice becoming more common in ART, there is a
      greater demand for a convenient and reliable cryostorage of surplus blastocysts.
      Vitrification has emerged in the last decade as an alternative promising
      substitute for slow freezing. Blastocysts represent a unique challenge in
      cryostorage due to their size, multicellular structure and presence of
      blastocoele. The continuous acquisition of experience and introduction of many
      different technological developments has led to the improvement of vitrification
      as a technology and improved the results of its application in blastocyst
      cryostorage. The current information concerning safety and efficacy of the
      vitrification of blastocysts will be reviewed along with the variables that can
      impact the outcome of the procedure.

PMID- 19758459
TI  - Mortality in sepsis versus non-sepsis induced acute lung injury.
AB  - INTRODUCTION: Sepsis-induced acute lung injury (ALI) has been reported to have a
      higher case fatality rate than other causes of ALI. However, differences in the
      severity of illness in septic vs. non-septic ALI patients might explain this
      finding. METHODS: 520 patients enrolled in the Improving Care of ALI Patients
      Study (ICAP) were prospectively characterized as having sepsis or non sepsis
      induced ALI. Biologically plausible risk factors for in-hospital death were
      considered in multiple logistic regression models to evaluate the independent
      association of sepsis vs. non-sepsis ALI risk factors with mortality. RESULTS:
      Patients with sepsis-induced ALI had greater illness severity and organ
      dysfunction (APACHE II and SOFA scores) at ALI diagnosis and higher crude in
      hospital mortality rates compared with non-sepsis ALI patients. Patients with
      sepsis-induced ALI received similar tidal volumes, but higher levels of positive
      end expiratory pressure, and had a more positive net fluid balance in the first
      week after ALI diagnosis. In multivariable analysis, the following variables
      (odds ratio, 95% confidence interval) were significantly associated with hospital
      mortality: age (1.04, 1.02 to 1.05), admission to a medical intensive care unit
      (ICU) (2.76, 1.42 to 5.36), ICU length of stay prior to ALI diagnosis (1.15, 1.03
      to 1.29), APACHE II (1.05, 1.02 to 1.08), SOFA at ALI diagnosis (1.17, 1.09 to
      1.25), Lung Injury Score (2.33, 1.74 to 3.12) and net fluid balance in liters in
      the first week after ALI diagnosis (1.06, 1.03 to 1.09). Sepsis did not have a
      significant, independent association with mortality (1.02, 0.59 to 1.76).
      CONCLUSIONS: Greater severity of illness contributes to the higher case fatality
      rate observed in sepsis-induced ALI. Sepsis was not independently associated with
      mortality in our study.

PMID- 19758460
TI  - Zooplankton diversity analysis through single-gene sequencing of a community
      sample.
AB  - BACKGROUND: Oceans cover more than 70% of the earth's surface and are critical
      for the homeostasis of the environment. Among the components of the ocean
      ecosystem, zooplankton play vital roles in energy and matter transfer through the
      system. Despite their importance, understanding of zooplankton biodiversity is
      limited because of their fragile nature, small body size, and the large number of
      species from various taxonomic phyla. Here we present the results of single-gene
      zooplankton community analysis using a method that determines a large number of
      mitochondrial COI gene sequences from a bulk zooplankton sample. This approach
      will enable us to estimate the species richness of almost the entire zooplankton
      community. RESULTS: A sample was collected from a depth of 721 m to the surface
      in the western equatorial Pacific off Pohnpei Island, Micronesia, with a plankton
      net equipped with a 2-m2 mouth opening. A total of 1,336 mitochondrial COI gene
      sequences were determined from the cDNA library made from the sample. From the
      determined sequences, the occurrence of 189 species of zooplankton was estimated.
      BLASTN search results showed high degrees of similarity (>98%) between the query
      and database for 10 species, including holozooplankton and merozooplankton.
      CONCLUSION: In conjunction with the Census of Marine Zooplankton and Barcode of
      Life projects, single-gene zooplankton community analysis will be a powerful tool
      for estimating the species richness of zooplankton communities.

PMID- 19758461
TI  - Relative power and sample size analysis on gene expression profiling data.
AB  - BACKGROUND: With the increasing number of expression profiling technologies,
      researchers today are confronted with choosing the technology that has sufficient
      power with minimal sample size, in order to reduce cost and time. These depend on
      data variability, partly determined by sample type, preparation and processing.
      Objective measures that help experimental design, given own pilot data, are thus
      fundamental. RESULTS: Relative power and sample size analysis were performed on
      two distinct data sets. The first set consisted of Affymetrix array data derived
      from a nutrigenomics experiment in which weak, intermediate and strong PPARalpha
      agonists were administered to wild-type and PPARalpha-null mice. Our analysis
      confirms the hierarchy of PPARalpha-activating compounds previously reported and
      the general idea that larger effect sizes positively contribute to the average
      power of the experiment. A simulation experiment was performed that mimicked the
      effect sizes seen in the first data set. The relative power was predicted but the
      estimates were slightly conservative. The second, more challenging, data set
      describes a microarray platform comparison study using hippocampal deltaC
      doublecortin-like kinase transgenic mice that were compared to wild-type mice,
      which was combined with results from Solexa/Illumina deep sequencing runs. As
      expected, the choice of technology greatly influences the performance of the
      experiment. Solexa/Illumina deep sequencing has the highest overall power
      followed by the microarray platforms Agilent and Affymetrix. Interestingly,
      Solexa/Illumina deep sequencing displays comparable power across all intensity
      ranges, in contrast with microarray platforms that have decreased power in the
      low intensity range due to background noise. This means that deep sequencing
      technology is especially more powerful in detecting differences in the low
      intensity range, compared to microarray platforms. CONCLUSION: Power and sample
      size analysis based on pilot data give valuable information on the performance of
      the experiment and can thereby guide further decisions on experimental design.
      Solexa/Illumina deep sequencing is the technology of choice if interest lies in
      genes expressed in the low-intensity range. Researchers can get guidance on
      experimental design using our approach on their own pilot data implemented as a
      BioConductor package, SSPA
      http://bioconductor.org/packages/release/bioc/html/SSPA.html.

PMID- 19758462
TI  - Beneficial effect of the oxygen free radical scavenger amifostine (WR-2721) on
      spinal cord ischemia/reperfusion injury in rabbits.
AB  - BACKGROUND: Paraplegia is the most devastating complication of thoracic or
      thoraco-abdominal aortic surgery. During these operations, an ischemia
      reperfusion process is inevitable and the produced radical oxygen species cause
      severe oxidative stress for the spinal cord. In this study we examined the
      influence of Amifostine, a triphosphate free oxygen scavenger, on oxidative
      stress of spinal cord ischemia-reperfusion in rabbits. METHODS: Eighteen male,
      New Zealand white rabbits were anesthetized and spinal cord ischemia was induced
      by temporary occlusion of the descending thoracic aorta by a coronary artery
      balloon catheter, advanced through the femoral artery. The animals were randomly
      divided in 3 groups. Group I functioned as control. In group II the descending
      aorta was occluded for 30 minutes and then reperfused for 75 min. In group III,
      500 mg Amifostine was infused into the distal aorta during the second half-time
      of ischemia period. At the end of reperfusion all animals were sacrificed and
      spinal cord specimens were examined for superoxide radicals by an ultra sensitive
      fluorescent assay. RESULTS: Superoxide radical levels ranged, in group I between
      1.52 and 1.76 (1.64 +/- 0.10), in group II between 1.96 and 2.50 (2.10 +/- 0.23),
      and in group III (amifostine) between 1.21 and 1.60 (1.40 +/- 0.19) (p = 0.00),
      showing a decrease of 43% in the Group of Amifostine. A lipid peroxidation marker
      measurement ranged, in group I between 0.278 and 0.305 (0.296 +/- 0.013), in
      group II between 0.427 and 0.497 (0.463 +/- 0.025), and in group III (amifostine)
      between 0.343 and 0.357 (0.350 +/- 0.007) (p < 0.00), showing a decrease of 38%
      after Amifostine administration. CONCLUSION: By direct and indirect methods of
      measuring the oxidative stress of spinal cord after ischemia/reperfusion, it is
      suggested that intra-aortic Amifostine infusion during spinal cord ischemia
      phase, significantly attenuated the spinal cord oxidative injury in rabbits.

PMID- 19758463
TI  - Between proteins and phenotypes: annotation and interpretation of mutations.

PMID- 19758464
TI  - Extraction of human kinase mutations from literature, databases and genotyping
      studies.
AB  - BACKGROUND: There is a considerable interest in characterizing the biological
      role of specific protein residue substitutions through mutagenesis experiments.
      Additionally, recent efforts related to the detection of disease-associated SNPs
      motivated both the manual annotation, as well as the automatic extraction, of
      naturally occurring sequence variations from the literature, especially for
      protein families that play a significant role in signaling processes such as
      kinases. Systematic integration and comparison of kinase mutation information
      from multiple sources, covering literature, manual annotation databases and large
      scale experiments can result in a more comprehensive view of functional,
      structural and disease associated aspects of protein sequence variants.
      Previously published mutation extraction approaches did not sufficiently
      distinguish between two fundamentally different variation origin categories,
      namely natural occurring and induced mutations generated through in vitro
      experiments. RESULTS: We present a literature mining pipeline for the automatic
      extraction and disambiguation of single-point mutation mentions from both
      abstracts as well as full text articles, followed by a sequence validation check
      to link mutations to their corresponding kinase protein sequences. Each mutation
      is scored according to whether it corresponds to an induced mutation or a natural
      sequence variant. We were able to provide direct literature links for a
      considerable fraction of previously annotated kinase mutations, enabling thus
      more efficient interpretation of their biological characterization and
      experimental context. In order to test the capabilities of the presented
      pipeline, the mutations in the protein kinase domain of the kinase family were
      analyzed. Using our literature extraction system, we were able to recover a total
      of 643 mutations-protein associations from PubMed abstracts and 6,970 from a
      large collection of full text articles. When compared to state-of-the-art
      annotation databases and high throughput genotyping studies, the mutation
      mentions extracted from the literature overlap to a good extent with the existing
      knowledgebases, whereas the remaining mentions suggest new mutation records that
      were not previously annotated in the databases. CONCLUSION: Using the proposed
      residue disambiguation and classification approach, we were able to differentiate
      between natural variant and mutagenesis types of mutations with an accuracy of
      93.88. The resulting system is useful for constructing a Gold Standard set of
      mutations extracted from the literature by human experts with minimal manual
      curation effort, providing direct pointers to relevant evidence sentences. Our
      system is able to recover mutations from the literature that are not present in
      state-of-the-art databases. Human expert manual validation of a subset of the
      literature extracted mutations conducted on 100 mutations from PubMed abstracts
      highlights that almost three quarters (72%) of the extracted mutations turned out
      to be correct, and more than half of these had not been previously annotated in
      databases.

PMID- 19758465
TI  - Pairwise and higher-order correlations among drug-resistance mutations in HIV-1
      subtype B protease.
AB  - BACKGROUND: The reaction of HIV protease to inhibitor therapy is characterized by
      the emergence of complex mutational patterns which confer drug resistance. The
      response of HIV protease to drugs often involves both primary mutations that
      directly inhibit the action of the drug, and a host of accessory resistance
      mutations that may occur far from the active site but may contribute to restoring
      the fitness or stability of the enzyme. Here we develop a probabilistic approach
      based on connected information that allows us to study residue, pair level and
      higher-order correlations within the same framework. RESULTS: We apply our
      methodology to a database of approximately 13,000 sequences which have been
      annotated by the treatment history of the patients from which the samples were
      obtained. We show that including pair interactions is essential for agreement
      with the mutational data, since neglect of these interactions results in order-of
      magnitude errors in the probabilities of the simultaneous occurence of many
      mutations. The magnitude of these pair correlations changes dramatically between
      sequences obtained from patients that were or were not exposed to drugs. Higher
      order effects make a contribution of as much as 10% for residues taken three at a
      time, but increase to more than twice that for 10 to 15-residue groups. The
      sequence data is insufficient to determine the higher-order effects for larger
      groups. We find that higher-order interactions have a significant effect on the
      predicted frequencies of sequences with large numbers of mutations. While
      relatively rare, such sequences are more prevalent after multi-drug therapy. The
      relative importance of these higher-order interactions increases with the number
      of drugs the patient had been exposed to. CONCLUSION: Correlations are critical
      for the understanding of mutation patterns in HIV protease. Pair interactions
      have substantial qualitative effects, while higher-order interactions are
      individually smaller but may have a collective effect. Together they lead to
      correlations which could have an important impact on the dynamics of the
      evolution of cross-resistance, by allowing the virus to pass through otherwise
      unlikely mutational states. These findings also indicate that pairwise and
      possibly higher-order effects should be included in the models of protein
      evolution, instead of assuming that all residues mutate independently of one
      another.

PMID- 19758466
TI  - EnzyMiner: automatic identification of protein level mutations and their impact
      on target enzymes from PubMed abstracts.
AB  - BACKGROUND: A better understanding of the mechanisms of an enzyme's functionality
      and stability, as well as knowledge and impact of mutations is crucial for
      researchers working with enzymes. Though, several of the enzymes' databases are
      currently available, scientific literature still remains at large for up-to-date
      source of learning the effects of a mutation on an enzyme. However, going through
      vast amounts of scientific documents to extract the information on desired
      mutation has always been a time consuming process. In this paper, therefore, we
      describe an unique method, termed as EnzyMiner, which automatically identifies
      the PubMed abstracts that contain information on the impact of a protein level
      mutation on the stability and/or the activity of a given enzyme. RESULTS: We
      present an automated system which identifies the abstracts that contain an amino
      acid-level mutation and then classifies them according to the mutation's effect
      on the enzyme. In the case of mutation identification, MuGeX, an automated
      mutation-gene extraction system has an accuracy of 93.1% with a 91.5 F-measure.
      For impact analysis, document classification is performed to identify the
      abstracts that contain a change in enzyme's stability or activity resulting from
      the mutation. The system was trained on lipases and tested on amylases with an
      accuracy of 85%. CONCLUSION: EnzyMiner identifies the abstracts that contain a
      protein mutation for a given enzyme and checks whether the abstract is related to
      a disease with the help of information extraction and machine learning
      techniques. For disease related abstracts, the mutation list and direct links to
      the abstracts are retrieved from the system and displayed on the Web. For those
      abstracts that are related to non-diseases, in addition to having the mutation
      list, the abstracts are also categorized into two groups. These two groups
      determine whether the mutation has an effect on the enzyme's stability or
      functionality followed by displaying these on the web.

PMID- 19758467
TI  - Improved mutation tagging with gene identifiers applied to membrane protein
      stability prediction.
AB  - BACKGROUND: The automated retrieval and integration of information about protein
      point mutations in combination with structure, domain and interaction data from
      literature and databases promises to be a valuable approach to study structure
      function relationships in biomedical data sets. RESULTS: We developed a rule- and
      regular expression-based protein point mutation retrieval pipeline for PubMed
      abstracts, which shows an F-measure of 87% for the mutation retrieval task on a
      benchmark dataset. In order to link mutations to their proteins, we utilize a
      named entity recognition algorithm for the identification of gene names co
      occurring in the abstract, and establish links based on sequence checks. Vice
      versa, we could show that gene recognition improved from 77% to 91% F-measure
      when considering mutation information given in the text. To demonstrate practical
      relevance, we utilize mutation information from text to evaluate a novel
      solvation energy based model for the prediction of stabilizing regions in
      membrane proteins. For five G protein-coupled receptors we identified 35 relevant
      single mutations and associated phenotypes, of which none had been annotated in
      the UniProt or PDB database. In 71% reported phenotypes were in compliance with
      the model predictions, supporting a relation between mutations and stability
      issues in membrane proteins. CONCLUSION: We present a reliable approach for the
      retrieval of protein mutations from PubMed abstracts for any set of genes or
      proteins of interest. We further demonstrate how amino acid substitution
      information from text can be utilized for protein structure stability studies on
      the basis of a novel energy model.

PMID- 19758468
TI  - Annotation of protein residues based on a literature analysis: cross-validation
      against UniProtKb.
AB  - BACKGROUND: A protein annotation database, such as the Universal Protein Resource
      knowledge base (UniProtKb), is a valuable resource for the validation and
      interpretation of predicted 3D structure patterns in proteins. Existing studies
      have focussed on point mutation extraction methods from biomedical literature
      which can be used to support the time consuming work of manual database curation.
      However, these methods were limited to point mutation extraction and do not
      extract features for the annotation of proteins at the residue level. RESULTS:
      This work introduces a system that identifies protein residues in MEDLINE
      abstracts and annotates them with features extracted from the context written in
      the surrounding text. MEDLINE abstract texts have been processed to identify
      protein mentions in combination with taxonomic species and protein residues (F1
      measure 0.52). The identified protein-species-residue triplets have been
      validated and benchmarked against reference data resources (UniProtKb, average F1
      measure of 0.54). Then, contextual features were extracted through shallow and
      deep parsing and the features have been classified into predefined categories (F1
      measure ranges from 0.15 to 0.67). Furthermore, the feature sets have been
      aligned with annotation types in UniProtKb to assess the relevance of the
      annotations for ongoing curation projects. Altogether, the annotations have been
      assessed automatically and manually against reference data resources. CONCLUSION:
      This work proposes a solution for the automatic extraction of functional
      annotation for protein residues from biomedical articles. The presented approach
      is an extension to other existing systems in that a wider range of residue
      entities are considered and that features of residues are extracted as
      annotations.

PMID- 19758469
TI  - An integrated approach to the interpretation of single amino acid polymorphisms
      within the framework of CATH and Gene3D.
AB  - BACKGROUND: The phenotypic effects of sequence variations in protein-coding
      regions come about primarily via their effects on the resulting structures, for
      example by disrupting active sites or affecting structural stability. In order
      better to understand the mechanisms behind known mutant phenotypes, and predict
      the effects of novel variations, biologists need tools to gauge the impacts of
      DNA mutations in terms of their structural manifestation. Although many mutations
      occur within domains whose structure has been solved, many more occur within
      genes whose protein products have not been structurally characterized. RESULTS:
      Here we present 3DSim (3D Structural Implication of Mutations), a database and
      web application facilitating the localization and visualization of single amino
      acid polymorphisms (SAAPs) mapped to protein structures even where the structure
      of the protein of interest is unknown. The server displays information on 6514
      point mutations, 4865 of them known to be associated with disease. These
      polymorphisms are drawn from SAAPdb, which aggregates data from various sources
      including dbSNP and several pathogenic mutation databases. While the SAAPdb
      interface displays mutations on known structures, 3DSim projects mutations onto
      known sequence domains in Gene3D. This resource contains sequences annotated with
      domains predicted to belong to structural families in the CATH database. Mappings
      between domain sequences in Gene3D and known structures in CATH are obtained
      using a MUSCLE alignment. 1210 three-dimensional structures corresponding to CATH
      structural domains are currently included in 3DSim; these domains are distributed
      across 396 CATH superfamilies, and provide a comprehensive overview of the
      distribution of mutations in structural space. CONCLUSION: The server is publicly
      available at http://3DSim.bioinfo.cnio.es/. In addition, the database containing
      the mapping between SAAPdb, Gene3D and CATH is available on request and most of
      the functionality is available through programmatic web service access.

PMID- 19758470
TI  - From SNPs to pathways: integration of functional effect of sequence variations on
      models of cell signalling pathways.
AB  - BACKGROUND: Single nucleotide polymorphisms (SNPs) are the most frequent type of
      sequence variation between individuals, and represent a promising tool for
      finding genetic determinants of complex diseases and understanding the
      differences in drug response. In this regard, it is of particular interest to
      study the effect of non-synonymous SNPs in the context of biological networks
      such as cell signalling pathways. UniProt provides curated information about the
      functional and phenotypic effects of sequence variation, including SNPs, as well
      as on mutations of protein sequences. However, no strategy has been developed to
      integrate this information with biological networks, with the ultimate goal of
      studying the impact of the functional effect of SNPs in the structure and
      dynamics of biological networks. RESULTS: First, we identified the different
      challenges posed by the integration of the phenotypic effect of sequence variants
      and mutations with biological networks. Second, we developed a strategy for the
      combination of data extracted from public resources, such as UniProt, NCBI dbSNP,
      Reactome and BioModels. We generated attribute files containing phenotypic and
      genotypic annotations to the nodes of biological networks, which can be imported
      into network visualization tools such as Cytoscape. These resources allow the
      mapping and visualization of mutations and natural variations of human proteins
      and their phenotypic effect on biological networks (e.g. signalling pathways,
      protein-protein interaction networks, dynamic models). Finally, an example on the
      use of the sequence variation data in the dynamics of a network model is
      presented. CONCLUSION: In this paper we present a general strategy for the
      integration of pathway and sequence variation data for visualization, analysis
      and modelling purposes, including the study of the functional impact of protein
      sequence variations on the dynamics of signalling pathways. This is of particular
      interest when the SNP or mutation is known to be associated to disease. We expect
      that this approach will help in the study of the functional impact of disease
      associated SNPs on the behaviour of cell signalling pathways, which ultimately
      will lead to a better understanding of the mechanisms underlying complex
      diseases.

PMID- 19758471
TI  - MtSNPscore: a combined evidence approach for assessing cumulative impact of
      mitochondrial variations in disease.
AB  - BACKGROUND: Human mitochondrial DNA (mtDNA) variations have been implicated in a
      broad spectrum of diseases. With over 3000 mtDNA variations reported across
      databases, establishing pathogenicity of variations in mtDNA is a major
      challenge. We have designed and developed a comprehensive weighted scoring system
      (MtSNPscore) for identification of mtDNA variations that can impact pathogenicity
      and would likely be associated with disease. The criteria for pathogenicity
      include information available in the literature, predictions made by various in
      silico tools and frequency of variation in normal and patient datasets. The
      scoring scheme also assigns scores to patients and normal individuals to estimate
      the cumulative impact of variations. The method has been implemented in an
      automated pipeline and has been tested on Indian ataxia dataset (92 individuals),
      sequenced in this study, and other publicly available mtSNP dataset comprising of
      576 mitochondrial genomes of Japanese individuals from six different groups,
      namely, patients with Parkinson's disease, patients with Alzheimer's disease,
      young obese males, young non-obese males, and type-2 diabetes patients with or
      without severe vascular involvement. MtSNPscore, for analysis can extract
      information from variation data or from mitochondrial DNA sequences. It has a web
      interface http://bioinformatics.ccmb.res.in/cgi-bin/snpscore/Mtsnpscore.pl that
      provides flexibility to update/modify the parameters for estimating
      pathogenicity. RESULTS: Analysis of ataxia and mtSNP data suggests that rare
      variants comprise the largest part of disease associated variations. MtSNPscore
      predicted possible role of eight and 79 novel variations in ataxia and mtSNP
      datasets, respectively, in disease etiology. Analysis of cumulative scores of
      patient and normal data resulted in Matthews Correlation Coefficient (MCC) of
      ~0.5 and accuracy of ~0.7 suggesting that the method may also predict involvement
      of mtDNA variation in diseases. CONCLUSION: We have developed a novel and
      comprehensive method for evaluation of mitochondrial variation and their
      involvement in disease. Our method has the most comprehensive set of parameters
      to assess mtDNA variations and overcomes the undesired bias generated as a result
      of better-studied diseases and genes. These variations can be prioritized for
      functional assays to confirm their pathogenic status.

PMID- 19758472
TI  - Correlating protein function and stability through the analysis of single amino
      acid substitutions.
AB  - BACKGROUND: Mutations resulting in the disruption of protein function are the
      underlying causes of many genetic diseases. Some mutations affect the number of
      expressed proteins while others alter the activity on a per-molecule basis.
      Single amino acid substitutions as caused by non-synonymous Single Nucleotide
      Polymorphisms (nsSNPs) often disrupt function by altering protein structure
      and/or stability, but can also wreak havoc by directly impacting functional
      binding sites. Given the experimental three-dimensional (3D) structure of a
      protein, we can try to differentiate between the "effect on structure/stability"
      and the "effect on binding". However, experimental 3D structures are available
      for only 1% of all known proteins; the magnitude of stability change caused by a
      given mutation is more widely available. RESULTS: Here, we analyze to which
      extent the functional effect of a mutation can be predicted from the effect on
      protein stability. We find that simple sequence-based methods succeed in
      predicting functional effects of nsSNPs. In fact, such methods consistently
      outperform approaches that predict functional change through the application of
      binary thresholds to stability change. We also observed that if stability is
      affected, functional change is easier to predict than when stability is not
      affected. CONCLUSION: Our results confirmed that stability change is somehow
      related to function change. However, we also show that the knowledge of stability
      changes in no way suffices to predict functional changes and that many function
      changing mutations have no effect on stability.

PMID- 19758473
TI  - Using structural bioinformatics to investigate the impact of non synonymous SNPs
      and disease mutations: scope and limitations.
AB  - BACKGROUND: Linking structural effects of mutations to functional outcomes is a
      major issue in structural bioinformatics, and many tools and studies have shown
      that specific structural properties such as stability and residue burial can be
      used to distinguish neutral variations and disease associated mutations. RESULTS:
      We have investigated 39 structural properties on a set of SNPs and disease
      mutations from the Uniprot Knowledge Base that could be mapped on high quality
      crystal structures and show that none of these properties can be used as a sole
      classification criterion to separate the two data sets. Furthermore, we have
      reviewed the annotation process from mutation to result and identified the
      liabilities in each step. CONCLUSION: Although excellent annotation results of
      various research groups underline the great potential of using structural
      bioinformatics to investigate the mechanisms underlying disease, the
      interpretation of such annotations cannot always be extrapolated to proteome wide
      variation studies. Difficulties for large-scale studies can be found both on the
      technical level, i.e. the scarcity of data and the incompleteness of the
      structural tool suites, and on the conceptual level, i.e. the correct
      interpretation of the results in a cellular context.

PMID- 19758474
TI  - Differential uptake and selective permeability of fusarochromanone (FC101), a
      novel membrane permeable anticancer naturally fluorescent compound in tumor and
      normal cells.
AB  - The differential accumulation of fluorescent molecules in tumorigenic versus
      normal cells is a well-reported phenomenon and is the basis for photodiagnostic
      therapy. Through the use of confocal microscopy, the kinetic uptake and
      accumulation of fusarochromanone (FC101) was determined in two lines of living
      tumorigenic cells of mesenchymal-epithelial origin and normal fibroblast cells.
      Like other fluorescent cationic molecules, FC101 showed increased accumulation in
      tumorigenic cells; however, unlike other molecules, it appeared to be accumulated
      in a time-dependent manner. Also, unlike traditional fluorescent cationic
      molecules, FC101, a potent inhibitor of cell growth, showed preferential
      inhibition of tumorigenic B-16 melanoma cells and MCF7 cells derived from breast
      cancer adenocarcinoma when compared to normal cardiac fibroblasts. Further
      analysis of FC101's physicochemical properties using both experimentally obtained
      and simulated values revealed the likelihood of membrane permeation and oral
      bioavailability of the compound. These physicochemical properties of FC101 were
      also used to predict its intracellular localization lending credence to data
      observed by confocal microscopy.

PMID- 19758475
TI  - Listener impressions of speakers with Parkinson's disease.
AB  - Parkinson's disease (PD) has several negative effects on speech production and
      communication. However, few studies have looked at how speech patterns in PD
      contribute to linguistic and social impressions formed about PD patients from the
      perspective of listeners. In this study, discourse recordings elicited from
      nondemented PD speakers (n = 18) and healthy controls (n = 17) were presented to
      30 listeners unaware of the speakers' disease status. In separate conditions,
      listeners rated the discourse samples based on their impressions of the speaker
      or of the linguistic content. Acoustic measures of the speech samples were
      analyzed for comparison with listeners' perceptual ratings. Results showed that
      although listeners rated the content of Parkinsonian discourse as linguistically
      appropriate (e.g., coherent, well-organized, easy to follow), the PD speakers
      were perceived as significantly less interested, less involved, less happy, and
      less friendly than healthy speakers. Negative social impressions demonstrated a
      relationship to changes in vocal intensity (loudness) and temporal
      characteristics (dysfluencies) of Parkinsonian speech. Our findings emphasize
      important psychosocial ramifications of PD that are likely to limit opportunities
      for communication and social interaction for those affected, because of the
      negative impressions drawn by listeners based on their speaking voice.

PMID- 19758476
TI  - Haptoglobin and serum amyloid A in bulk tank milk in relation to raw milk
      quality.
AB  - The aim of the present study was to evaluate relationships between the presence
      of the two major bovine acute phase proteins haptoglobin (Hp) and serum amyloid A
      (SAA) and raw milk quality parameters in bulk tank milk samples. Hp and SAA have
      been suggested as specific markers of mastitis but recently also as markers for
      raw milk quality. Since mastitis has detrimental effects on milk quality, it is
      important to investigate whether the presence of Hp or SAA indicates such changes
      in the composition and properties of the milk. Bulk tank milk samples (n=91) were
      analysed for Hp, SAA, total protein, casein, whey protein, proteolysis, fat,
      lactose, somatic cell count and coagulating properties. Samples with detectable
      levels of Hp had lower casein content, casein number and lactose content, but
      higher proteolysis than samples without Hp. Samples with detectable levels of SAA
      had lower casein number and lactose content, but higher whey protein content than
      samples without SAA. The presence of acute phase proteins in bulk tank milk is
      suggested as an indicator for unfavourable changes in the milk composition, e.g.
      protein quality, due to udder health disturbances, with economical implications
      for the dairy industry.

PMID- 19758477
TI  - Influence of milk yield, stage of lactation, and body condition on dairy cattle
      lying behaviour measured using an automated activity monitoring sensor.
AB  - Time spent lying by lactating Holstein-Friesian cows of varying body condition
      scores (BCS) and milk yield was measured using an animal activity monitor. A 3
      week average BCS was calculated for each cow; and in total, 84 cows were selected
      with 28 cows each among three BCS categories (Thin: BCS<2.75; Moderate: 2.75 > or
      = BCS<3.25; Heavy: BCS> or = 3.25) and two stage of lactation categories (<150
      days in milk or >150 days in milk). Cows were kept in two management systems:
      parlour/freestall (n=60) or automated milking system/freestall (n=24). Behaviour
      was recorded for 5.3+/-0.1 d for each cow. Production levels were considered
      using a 28-d rolling average of daily milk production. Cows that exhibited
      clinical lameness before or during the observation period were excluded from
      analyses. For cows exhibiting oestrus, the day prior to, day of, and day
      following breeding were removed. The final analysis included 77 cows (408 d of
      observation). A mixed model was fitted to describe average daily hours spent
      lying. Results demonstrated that lying time increased as days in milk (DIM)
      increased (P=0.05). Variables that were tested but not significant (P>0.05) were
      BCS category, parity category (1 or 2) and 28-d rolling average daily milk
      production. Although a numerical trend for increasing hours spent lying with
      increasing BCS was observed, after accounting for other factors in the mixed
      model, BCS did not significantly impact lying time. Continued investigation of
      these management factors that impact lying time and bouts, using new
      technologies, more cows, and more herds will help dairy owners better manage
      facilities and cow movements to optimize this essential behaviour.

PMID- 19758478
TI  - Reliability of the bulk milk somatic cell count as an indication of average herd
      somatic cell count.
AB  - Bulk milk somatic cell count (BMSCC) is a frequently used parameter to estimate
      the subclinical mastitis prevalence in a dairy herd, but it often differs
      considerably from the average SCC of all individual cows in milk. In this study,
      first the sampling variation was determined on 53 dairy farms with a BMSCC
      ranging from 56 000 to 441 000 cells/ml by collecting five samples on each farm
      of the same bulk tank. The average absolute sampling variation ranged from 1800
      to 19 800 cells/ml. To what extent BMSCC represents all lactating cows was
      evaluated in another 246 farms by comparing BMSCC to the average herd SCC
      corrected for milk yield (CHSCC), after the difference was corrected for the
      sampling variation of BMSCC. On average BMSCC was 49 000 cells/ml lower than
      CHSCC, ranging from -10 000 cells/ml to 182 000 cells/ml, while the difference
      increased with an increasing BMSCC. Subsequently, management practices associated
      with existing differences were identified. Farms with a small (<20%) difference
      between BMSCC and CHSCC administered intramuscular antibiotics for the treatment
      of clinical mastitis more often, used the high SCC history when cows were dried
      off more frequently and had a higher number of treatments per clinical mastitis
      case compared with farms with a large (20%) difference. Farms feeding high-SCC
      milk or milk with antibiotic residues to calves were 2.4-times more likely to
      have a large difference. Although sampling variation influences the differences
      between BMSCC and CHSCC, the remaining difference is still important and should
      be considered when BMSCC is used to review the average herd SCC and the
      subclinical mastitis prevalence.

PMID- 19758479
TI  - Validity of the Bouchard activity diary in Spanish adolescents.
AB  - OBJECTIVE: Valid and simple instruments to assess physical activity (PA) in
      specific populations are required for health-related research. The aim of the
      present study was to assess the validity of the Bouchard activity diary (AD) in
      Spanish adolescents using an activity monitor to compare total PA and moderate-to
      vigorous PA (MVPA) obtained by both instruments. DESIGN: Sixty-one Spanish
      adolescents, aged 12-16 years, completed the Bouchard AD and wore the ActiGraph
      activity monitor for three consecutive days. Validity was assessed with the
      Spearman correlation coefficient (rho), the Bland-Altman method and the kappa
      coefficient. RESULTS: Thirty-seven adolescents were included in the final
      analysis. Correlations between the activity monitor and the AD administered over
      the three days (Thursday-Saturday) were moderate (rho = 0.33-0.35, P < 0.05) or
      non-significant for total PA and moderate (rho = 0.36, P < 0.05) for MVPA.
      Correlations between the two methods were progressively lower for each subsequent
      day of testing, for both total PA and MVPA. The Bland-Altman plot illustrated
      that the Bouchard AD overestimated MVPA (mean difference -32.05 (sd 74.56) min;
      95 % limits of agreement 109.61, -173.31 min). Agreements for classification into
      MVPA tertiles and accordance with the international recommendations of MVPA were
      fair and moderate, respectively, for the 3 d means. CONCLUSIONS: The Bouchard AD
      has reasonable validity to assess total PA and MVPA in Spanish adolescents. The
      results show lower levels of agreement on the third day but it is not clear if
      this is due to design features (weekday v. weekend) or to participant compliance
      with the survey or the activity monitoring protocol.

PMID- 19758480
TI  - Food consumption and nutritional status of people living with HIV/AIDS (PLWHA): a
      case of Thika and Bungoma Districts, Kenya.
AB  - OBJECTIVE: To establish the food consumption, dietary habits and nutritional
      status of people living with HIV/AIDS (PLWHA) and adults whose HIV status is not
      established. DESIGN: Cross-sectional descriptive survey. SETTING: Thika and
      Bungoma Districts, Kenya. SUBJECTS: A random sample of 439 adults; 174 adults
      living with HIV/AIDS and 265 adults whose HIV/AIDS status was not established in
      Thika and Bungoma Districts. RESULTS: Majority of PLWHA consume foods that are
      low in nutrients to build up the immune system and help maintain adequate weight,
      and there is little variety in the foods they consume. More adults who are HIV
      positive are undernourished than those whose status is not established. Of the
      HIV-positive adults, those with a BMI of <or=18.5 kg/m2 were 23.6 % (Thika 20.0 %
      and Bungoma 25.7 %) while of the adults whose status is not established those
      with BMI <or= 18.5 kg/m2 were 13.9 % (Thika 9.3 % and Bungoma 16.7 %).
      CONCLUSIONS: Adults who are HIV-positive are more likely to be undernourished
      than those whose status is not established, as there is a significant difference
      (P = 0.000) between the nutritional status (BMI) of PLWHA and those whose
      HIV/AIDS status is not established. PLWHA consume foods that are low in nutrients
      to promote their nutritional well-being and health.

PMID- 19758481
TI  - Cost-effectiveness of mandatory folate fortification v. other options for the
      prevention of neural tube defects: results from Australia and New Zealand.
AB  - OBJECTIVE: To provide input to Australian and New Zealand government decision
      making regarding an optimal strategy to reduce the rate of neural tube defects
      (NTD). DESIGN: Standard comparative health economic evaluation techniques were
      employed for a set of intervention options for promoting folate/folic acid
      consumption in women capable of or planning a pregnancy. Evidence of
      effectiveness was informed by the international literature and costs were derived
      for Australia and New Zealand. RESULTS: Population-wide campaigns to promote
      supplement use and mandatory fortification were the most effective at reducing
      NTD, at an estimated 36 and 31 fewer cases per annum respectively for Australia
      and New Zealand, representing an 8 % reduction in the current annual NTD rate.
      Population-wide and targeted approaches to increase supplement use were cost
      effective, at less than $AU 12,500 per disability-adjusted life year (DALY)
      averted ($US 9893, pound 5074), as was extending voluntary fortification.
      Mandatory fortification was not cost-effective for New Zealand at $AU 138,500 per
      DALY ($US 109 609, pound 56,216), with results uncertain for Australia, given
      widely varying cost estimates. Promoting a folate-rich diet was least cost
      effective, with benefits restricted to impact on NTD. CONCLUSIONS: Several
      options for reducing NTD appear to fall well within accepted societal cost
      effectiveness norms. All estimates are subject to considerable uncertainty,
      exacerbated by possible interactions between interventions, including impacts on
      currently effective strategies. The Australian and New Zealand governments have
      decided to proceed with mandatory fortification; it is hoped they will support a
      rigorous evaluation which will contribute to the evidence base.

PMID- 19758482
TI  - Prediction of hypertension by different anthropometric indices in adults: the
      change in estimate approach.
AB  - OBJECTIVE: To examine the relative contribution for the prediction of
      hypertension by waist circumference (WC), waist:stature ratio (WSR) or waist:hip
      ratio (WHR) with that by BMI, to ascertain if WC, WSR or WHR enhances the
      prediction of hypertension by BMI. DESIGN: Population-based, cross-sectional
      study. A change of >or=10 % in the prevalence ratio of BMI (PR) or the area under
      the receiver-operating characteristic curve (AUC) when WC, WSR or WHR was added
      to a model with BMI was used as the criterion for significant contribution to the
      prediction of hypertension by BMI. For greater contributions (>or=10 %) these
      waist measures were considered as better predictors. SETTING: Nine provinces in
      China. SUBJECTS: Chinese adults aged 18 to 65 years (n 7336) who participated in
      the 2004 China Health and Nutrition Survey. RESULTS: The prevalence of
      hypertension (17 % and 23 % for women and men, respectively) was significantly
      related to increased BMI, WC, WSR and WHR (P for trend <0.001). Although there
      was a better model fit when WC, WSR or WHR was added to a model with BMI (P <
      0.05; likelihood ratio test), the changes in PR and AUC were <10 % and <5 %,
      respectively. The sex-specific AUC for the prediction of hypertension by BMI (of
      0.7-0.8) was similar to that by WC, WSR or WHR. CONCLUSIONS: The waist indices do
      not perform better than BMI or markedly enhance the prediction of increased
      hypertension risk by BMI in Chinese adults.

PMID- 19758483
TI  - Association between intake of dietary protein and 3-year-change in body growth
      among normal and overweight 6-year-old boys and girls (CoSCIS).
AB  - OBJECTIVE: Growth hormone (GH) affects linear growth and body composition, by
      increasing the secretion of insulin-like growth factor-I (IGF-I), muscle protein
      synthesis and lipolysis. The intake of protein (PROT) as well as the specific
      amino acids arginine (ARG) and lysine (LYS) stimulates GH/IGF-I secretion. The
      present paper aimed to investigate associations between PROT intake as well as
      intake of the specific amino acids ARG and LYS, and subsequent 3-year-change in
      linear growth and body composition among 6-year-old children. DESIGN: Children's
      data were collected from Copenhagen (Denmark), during 2001-2002, and again 3
      years later. Boys and girls were separated into normal weight and overweight,
      based on BMI quintiles. Fat-free mass index (FFMI) and fat mass index (FMI) were
      calculated. Associations between change (Delta) in height, FMI and FFMI,
      respectively, and habitual PROT intake as well as ARG and LYS were analysed by
      multiple linear regressions, adjusted for baseline height, FMI or FFMI and energy
      intake, age, physical activity and socio-economic status. SETTING: Eighteen
      schools in two suburban communities in the Copenhagen (Denmark) area participated
      in the study. SUBJECTS: In all, 223 children's data were collected for the
      present study. RESULTS: High ARG intake was associated with linear growth (beta =
      1.09 (se 0.54), P = 0.05) among girls. Furthermore, in girls, DeltaFMI had a
      stronger inverse association with high ARG intake, if it was combined with high
      LYS intake, instead of low LYS intake (P = 0.03). No associations were found in
      boys.ConclusionIn prepubertal girls, linear growth may be influenced by habitual
      ARG intake and body fat gain may be relatively prevented over time by the intake
      of the amino acids ARG and LYS.

PMID- 19758484
TI  - The prevalence and determinants of breast-feeding initiation and duration in a
      sample of women in Ireland.
AB  - OBJECTIVE: To assess breast-feeding initiation and prevalence from birth to 6
      months in a sample of mothers in Dublin, and to determine the factors associated
      with breast-feeding initiation and 'any' breast-feeding at 6 weeks in a sample of
      Irish-national mothers. DESIGN: This prospective cross-sectional study involved
      the recruitment of women during the antenatal period, with subsequent follow-up
      of mothers who delivered healthy, term singleton infants, at 6 weeks and 6 months
      postpartum. SETTING: Participants were recruited from antenatal clinics in the
      Coombe Women and Infants University Hospital, Dublin. SUBJECTS: In all, 401 Irish
      national and forty-nine non-Irish-national mothers met the criteria for inclusion
      in the present study. RESULTS: Breast-feeding initiation rates of the Irish
      national and non-Irish-nationals were 47% and 79.6%, respectively. Factors that
      were significantly (P = 0.000) associated with both breast-feeding initiation and
      'any' breast-feeding at 6 weeks included mothers who were >or=35 years, educated
      to third level, reported positive postnatal encouragement to breast-feed from
      their partners and had a positive antenatal intention to breast-feed. The
      maternal negative perception that breast-feeding is an embarrassing way to feed
      an infant was demonstrated as a major barrier to initiation. CONCLUSIONS: Breast
      feeding initiation and prevalence rates of the Irish-national population remain
      low and lag considerably behind national and international targets. Inclusion of
      the partner in breast-feeding promotional initiatives during the antenatal period
      may be crucial to increase breast-feeding rates in Ireland. Public health
      campaigns that focus on increasing the social acceptability of breast-feeding may
      prove effective in addressing this cultural barrier.

PMID- 19758485
TI  - Differential involvement of beta3 integrin in pre- and postsynaptic forms of
      adaptation to chronic activity deprivation.
AB  - Neuronal networks can adapt to global changes in activity levels through
      compensatory modifications in pre- and postsynaptic parameters of synaptic
      transmission. These forms of synaptic plasticity are known as synaptic
      homeostasis, and are thought to require specific cellular interactions and
      signaling across the entire neuronal network. However, the molecular mechanisms
      underlying synaptic homeostasis have so far been investigated mostly in primary
      cultures of dissociated neurons, a preparation that lacks the specificity of in
      vivo circuitry. Here, we show that there are critical differences in the
      properties of synaptic homeostasis between dissociated neuronal cultures and
      organotypic slices, a preparation that preserves more precisely in vivo
      connectivity. Moreover, the cell adhesion molecule beta3 integrin, which
      regulates excitatory synaptic strength, is specifically required for a
      postsynaptic form of synaptic homeostasis called synaptic scaling in both
      dissociated cultures and organotypic slices. Conversely, another form of synaptic
      homeostasis that involves changes in presynaptic quantal content occurs
      independently of beta3 integrin. Our findings define the differential involvement
      of beta3 integrin in two forms of synaptic homeostasis.

PMID- 19758486
TI  - Skewed sex ratio at birth in India.
AB  - Scientists commonly use world average data on sex ratio at birth for India for
      want of dependable ones. Here an attempt is made to redress the problem to some
      extent. It is shown that this ratio has been high in India since the 1950s. The
      ratio has been strikingly high, even prior to the time of inception of prenatal
      sex identification technologies. The ratio shows a rising trend due to several
      biological reasons. In addition, it has been rising sharply for a couple of
      decades due to some socio-medical factors. The natural sex ratio at birth in
      India is noticeably higher than the world average.

PMID- 19758487
TI  - Mate choice in Olivenza: influence of border change on Spanish-Portuguese
      lineages.
AB  - The mating pattern in a population determines the next generation gene pool and
      therefore its genetic structure. Besides socio-cultural and geographic factors,
      political barriers may influence the formation of couples. The present paper
      studies how the change of national border affected the mating pattern of Olivenza
      in Badajoz Province (Spain), which experienced a change of domain from Portugal
      to Spain in 1801. For the period analysed (1750-1850), 954 Catholic marriage
      records were transcribed. Data were sorted by decades in order to make a temporal
      study possible and analysed by means of diversity and repeated-pairs of surnames.
      Following the change of border the mating pattern modified. Coinciding with a
      larger number of mixed marriages with Spaniards, there was a progressive rise in
      the diversity of surnames. From 1811 to 1820 the analysis of repeated-pairs of
      surnames indicates the existence of preferential matings within Spanish and
      Portuguese lineages. After 1821 the above pattern became less clear due to the
      disappearance of the Spanish-Portuguese restrictions on choice of mate.

PMID- 19758488
TI  - Symptom complaints following combat-related traumatic brain injury: relationship
      to traumatic brain injury severity and posttraumatic stress disorder.
AB  - Patients with a history of mild (n = 134) or moderate-to-severe (n = 91) TBI were
      asked to complete the Neurobehavioral Symptom Inventory (NSI) and the
      Posttraumatic Stress Disorder Checklist. Consistent with prior research,
      significantly more postconcussion symptoms were endorsed by the mild group. After
      controlling for age, time since injury, and mechanism of injury, TBI severity
      continued to be significantly related to postconcussion complaints on the NSI.
      However, after controlling for these same variables, along with posttraumatic
      stress disorder symptom severity, there no longer were differences between the
      TBI severity groups. That is, patients with mild TBI did not endorse
      significantly more complaints (adjusted mean = 22.4) than the moderate-to-severe
      group (adjusted mean = 21.8). These findings suggest that much of the symptom
      complaints in mildly injured patients may be due to emotional distress.

PMID- 19758489
TI  - [Women with acute coronary disease syndrome symptoms--the difficult diagnosis].

PMID- 19758490
TI  - [Recurrent case of Takotsubo syndrome].
AB  - We report the first case in Denmark of a woman with three episodes of transient
      myocardial injury (Takotsubo or stress cardiomyopathy). The condition, which
      mimicks acute myocardial infarction with chest pain, electrocardiographic changes
      and slightly elevated coronary enzymes has been explained by exaggerated
      sympathetic activity in the apical region of the left ventricle during emotional
      or physical stress causing apical ballooning. Despite this, coronary arteries are
      usually normal and ballooning is reversible.

PMID- 19758491
TI  - [Stress-induced Takotsubo cardiomyopathy].
AB  - A case of Takotsubo cardiomyopathy is described in a postmenopausal woman
      admitted for suspected recent myocardial infarction, triggered by significant
      social stress during a family Christmas dinner. Coronary angiography showed no
      significant lesions. Acute echocardiography demonstrated apical ballooning and an
      ejection fraction of 30%. The clinical course was uneventful and after one month,
      echocardiography showed complete resolution of the apical ballooning and recovery
      of left ventricular systolic function.

PMID- 19758492
TI  - [Takotsubo stress cardiomyopathy with mural thrombosis].
AB  - Takotsubo-cardiomyopathy is a stress-related acute cardiac disorder characterized
      by reversible systolic ballooning and hypokinesia of the distal part of the left
      ventricle, cardiac symptoms, and ECG-changes, but no coronary artery stenosis,
      and no other causable disease. In the present case, heart disease was suspected
      because of tachycardia and dyspnoea which continued after treatment for severe
      asthma. A mural thrombosis was an extraordinary finding in this otherwise typical
      case.

PMID- 19758493
TI  - [Water-pipe smoking--a survey of a Cochrane review].
AB  - More than half the younger population in Denmark have tried water-pipe smoking,
      but very few smoke daily or weekly. Water-pipe smoke contains approximately the
      same harmful substances as cigarette smoke. Accordingly, it is expected that
      water-pipe smoking will have the same harmful effect on health and be as
      addictive as other forms of tobacco smoking. The limited epidemiologic evidence
      seems to indicate that water-pipe smoking is as damaging to health as other forms
      of tobacco smoking. A Cochrane-review did not find a single study of water-pipe
      smoking cessation.

PMID- 19758494
TI  - [Analysis of quality data based on national clinical databases].
AB  - There is little agreement on the philosophy of measuring clinical quality in
      health care. How data should be analyzed and transformed to healthcare
      information is an ongoing discussion. To accept a difference in quality between
      health departments as a real difference, one should consider to which extent the
      selection of patients, random variation, confounding and inconsistency may have
      influenced results. The aim of this article is to summarize aspects of clinical
      healthcare data analyses provided from the national clinical quality databases
      and to show how data may be presented in a way which is understandable to readers
      without specialised knowledge of statistics.

PMID- 19758495
TI  - [Cardiac computer tomography in the investigation of atypical chest pain].
AB  - INTRODUCTION: Coronary CT angiography (CTA) is a promising method used for
      diagnostic evaluation of patients suspected of coronary artery disease (CAD). CTA
      is increasingly used as an alternative to conventional coronary angiography.
      Information on the diagnostic and therapeutic consequences of using CTA in the
      diagnostic work-up of patients suspected of CAD is sparse. MATERIAL AND METHODS:
      Out-clinic patients (n = 215) with chest pain and an intermediate pre-test
      probability of CAD were referred to diagnostic evaluation by CTA. RESULTS: CTA
      was not performed in 5% (11/215) due to extensive coronary calcification or
      arrhythmia, was non-conclusive in 7% (15/215) and was diagnostic in 88% (189/215)
      of the patients. CTA excluded CAD in 46% (99/215) of the patients. No further
      diagnostic or hospital follow-up after CTA was necessary in 73% (156/215) of the
      patients. CTA identified non-significant CAD in 27% (57/215) and significant CAD
      (>or= 50% stenosis) in 15% (33/215) of the patients. The proportion of patients
      with CAD in relevant antithrombotic and lipid-lowering medication increased
      following CTA. Further diagnostic evaluation with coronary angiography following
      CTA was indicated in 18% (39/215) of the patients due to obstructive CAD (n =
      21), non-diagnostic examination (n = 7), or the presence of extensive coronary
      calcification or arrhythmia (n = 11). CONCLUSION: CTA ruled-out CAD in 46% of the
      patients. No further diagnostic testing or hospital follow-up after CTA was
      necessary in 73% of the patients. CTA seems valuable in excluding CAD, and may
      prevent unnecessary invasive angiography in patients without CAD.

PMID- 19758496
TI  - [Retrograde intrarenal stone surgery--a minimally invasive method for treatment
      of minor kidney stones].
AB  - Retrograde intrarenal stone surgery (RIRS) is a safe and effective minimally
      invasive method for the treatment of minor (< 1.5 cm) kidney stones. This
      modality is the preferred treatment for minor ESWL-resistant kidney stones where
      resistance is due e.g. to anatomical abnormalities or stones of specific
      composition. The use of ureteric tone-modulating drugs in the irrigation fluid
      during the endoscopic procedure may prove to increase efficacy and safety of RIRS
      in the future.

PMID- 19758497
TI  - [Terminal phase hydration, pain and delirium].
AB  - Hydration of the terminal patient may relieve confusion and complaints of "dry
      mouth". But it may worsen oedema of the brain, lungs, and extremities, worsen
      terminal rattling and cause a need for frequent changing of diapers. The decision
      of whether and how to treat a dying patient with fluids should therefore be an
      integral part of the terminal treatment plan. Such plans should be discussed with
      the patient and the relatives, and it will very likely need to be revised as the
      condition worsens.

PMID- 19758498
TI  - [Evaluation of trainee doctors' skills].
AB  - The objective was to perform a needs assessment of trainee doctors' competences
      within lumbar puncture and bone marrow aspiration in paediatric oncology. Audit
      of 30 medical records revealed that five procedures, i.e. collegial, supervised
      administration of chemotherapy, examination of the child, length of bone marrow
      biopsy, erythrocytes in cerebrospinal fluid, and documentation of procedures in
      the medical record, were only handled as intended in half of the cases. Education
      and supervision of trainee doctors should be prioritized in order to increase
      their competences and decrease the risk of critical incidents.

PMID- 19758499
TI  - [Infantile haemangioma and intracranial vascular malformation].
AB  - A two-week-old female infant presented with a large haemangioma in the left
      superior palpebra, preventing her from opening the eye. Cerebral magnetic
      resonance imaging with angiography revealed another two facial haemangiomas and
      agenesia of the left internal carotid artery. The combination of facial
      haemangiomas and intracranial vascular malformation is diagnostic for the PHACES
      syndrome. When given oral prednisolone, the haemangioma regressed, allowing her
      to open the eye. She was treated for 29 weeks with slow tapering. Growth
      stagnation occurred during treatment, but otherwise her development was normal.

PMID- 19758500
TI  - [Gastrointestinal symptoms predominant in refugee children with malaria].
AB  - We present three cases of malaria in refugee children newly arrived from Sub
      saharan Africa. Only one of the three children had fever and all had high
      parasite loads (2,5-14% parasitemia). Malaria is an important differential
      diagnosis in refugees from endemic areas, regardless of whether they present with
      fever.

PMID- 19758501
TI  - [Cocaine-triggered ischaemic enteritis].
AB  - A 25-year-old woman was hospitalized repeatedly during a 5-year period due to
      abdominal pain, change in stool pattern, high CRP and leucocytosis. Ultrasound
      and small bowel examination showed oedema of terminal ileum, and morbus Crohn was
      initially suspected. A later ileocolonoscopy with biopsy and a pill cam capsule
      endoscopy were normal. In all cases the condition normalized spontaneously. A
      thorough interview revealed a recreational use of cocaine, and diary recordings
      confirmed the association between her abdominal pain and cocaine use. Ischaemic
      enteritis has previously been described in cocaine users.

PMID- 19758502
TI  - [Changes in Danish Medical Bulletin].

PMID- 19758503
TI  - [Indirect tuberculosis diagnostics. Has the Mantoux test got a successor?].

PMID- 19758504
TI  - [Comparison of QuantiFERON and tuberculin skin test in possible suspected
      tuberculosis infection].
AB  - INTRODUCTION: Two cases of tuberculosis were diagnosed at a high school. A
      contact investigation using Mantoux test (TST) and QuantiFERON TB in Tube test
      (QFT) was conducted in order to compare QFT with TST. METHODS: A total of 787
      individuals were invited to participate, of whom 734 had a TST applied and 490 a
      QFT test done. RESULTS: Of the skin test applied 689 (94%) were read, and 41
      (5.9%) were positive. TSTs were positive in 17/603 (2.8%) students and 24/87
      (28%) staff members. A total of 490 (62%) had a QFT performed; 11 (2.2%) were
      positive and four (0,8%) inconclusive. QFT positive results were found in 8/419
      (1.9%) students and 3/71 (4.2%) staff members. Agreement between the TST and the
      QFT was moderate 97% (Kappa 0.407; confidence interval (CI) 0.124-0.689) among
      students and poor among staff 68% (Kappa 0.036; CI -0.102-0.175). The majority of
      the TST-positive and all the QFT positive students were found in relation to the
      index case. Positive TST results and BCG vaccination (p < 0,05) were associated.
      Only 5/10 (50%) of the QFT-positive individuals were TST positive, which
      indicates a suboptimal TST sensitivity. CONCLUSION: The two tests identified an
      equal amount of Mycobacterium tuberculosis infected students, whereas a high
      proportion of the staff were TST positive. The discordant results underline that
      the two tests do not measure the same and that their sensitivity is not
      identical. Choice of test should rest on a case-by-case analysis and should be
      tailored to the desired level of safety and the cost for society and for the
      patients.

PMID- 19758505
TI  - [Interferon-gamma release assay on suspicion of active tuberculosis?].
AB  - INTRODUCTION: The purpose of this retrospective study was to outline the
      practical use and clinical value of the immunodiagnostic interferon-gamma release
      assay (IGRA) on suspicion of active Mycobacterium tuberculosis (TB) infection.
      MATERIAL AND METHODS: A retrospective study of all patients (n=91) tested with
      IGRA (Quantiferon-TB-Gold, Celletis International, Australia) for M. tuberculosis
      infection from 1 January 2005 to the 31 December 2006 at a Danish regional
      hospital. RESULTS: In 74 patients suspected of active TB, the sensitivity of IGRA
      was 80% (8/10), the specificity was 85% (50/59), PPV was 47% (8/17) and NPV was
      96% (50/52). The positive likelihood ratio (LR) was 5.3 and the negative LR was
      0.24. Due to a suboptimal diagnostic setup, the diagnosis of lung cancer in one
      patient was delayed significantly by a positive IGRA. CONCLUSION: In the current
      study, IGRA had a high false-positive rate for diagnosing active TB and had a
      rather low sensitivity which is in line with recent meta analyses. The
      physicians' use and judgement of this new test seemed suboptimal, as the
      overwhelming use of IGRA for suspected active TB was not in concordance with
      international guidelines. IGRA does not differentiate between active and latent
      M. tuberculosis infection, and IGRA may seldomly be used as a supplementary
      evaluative tool (with many false negative and "false positive" results).

PMID- 19758506
TI  - [New diagnostic test for tuberculosis].
AB  - The performance of two commercially-available Interferon Gamma Release Assays,
      QuantiFERON-TB-Gold and T-SPOT-TB, is reviewed. The tests can indirectly detect
      M. tuberculosis infection based on T-cell recognition of specific proteins which
      are not present in the BCG vaccine M. avium, or most other environmental
      mycobacteria.The sensitivity (76-88%) of the IGRAs is not optimal for a
      diagnostic test for active tuberculosis. However, the specificity is high (92
      97%), and the IGRAs may play an important role in the investigation for active
      tuberculosis and screening for latent tuberculosis infection in BCG vaccinated
      populations and immunosuppressed patients.

PMID- 19758507
TI  - [The myelodysplastic syndrome and autoimmunity].
AB  - INTRODUCTION: An increased incidence of autoimmune diseases has been reported in
      patients with myelodysplastic syndrome (MDS). The aim of the present study was to
      determine whether this association includes Danish MDS-patients. A possible
      association between autoimmune comorbidity and French-American-British
      Classification of Myelodysplastic Syndrome (FAB) or karyotype was also
      investigated. MATERIAL AND METHODS: The study is based on retrospective
      examination of medical records. The patients included in this study were
      identified by a search in Fyns Amts Sygehusvaesens Patientregister. Patients
      diagnosed with MDS from 2001 to 2005 were included. The search resulted in
      inclusion of 64 patients. On the basis of their autoimmune status, patients were
      divided into two groups: One group with MDS and autoimmune comorbidity and one
      group with only MDS. The two groups were compared by non-parametric statistics.
      RESULTS: There was a significantly increased incidence of autoimmune disease in
      patients with MDS. It was not possible to demonstrate an association between
      autoimmune comorbidity and age, sex, FAB- or karyotype. CONCLUSION: The present
      study shows an increased incidence of autoimmune disease among Danish patients
      with MDS which is in accordance with the majority of previous studies on this
      issue. Data suggests that treatment of autoimmune comorbidity may also improve
      some of the clinical and biochemical features of MDS.

PMID- 19758508
TI  - [Forensic anthropology].
AB  - Forensic anthropology is the application of biological or physical anthropology
      in the service of justice. One main area is the analysis of human remains. Such
      analyses involve person identification by assessment of age and sex of the
      deceased, and comparison with ante-mortem data. Another major area is the
      analysis of surveillance pictures and videos. Such analyses may comprise facial
      and bodily morphological comparisons, multi-angle photogrammetry and gait
      analysis. We also perform studies of human remains for archaeologists.

PMID- 19758509
TI  - [Does the mounting of gastrointestinal biopsies on millipore filter contribute to
      an improved section quality?].
AB  - INTRODUCTION: The quality of the histological sections of gastrointestinal
      biopsies (GIB) affects the diagnostic possibilities. One aspect is the
      orientation of GIB, whereby sectioning perpendicular to the mucosal surface can
      be performed more readily. With the purpose to achieve correct orientation, GIB
      is occasionally mounted on millipore filter (MF) in an attempt to place the deep
      cut side onto the MF. The importance of this technique for section quality is
      evaluated in this study. MATERIAL AND METHOD: The material comprised three
      consecutive series of GIB (60 gastric, duodenal, and colorectal GIB,
      respectively). Sections were grouped in MF-mounted versus non-mounted GIB, the
      proportion of fully acceptable sections among mounted versus non-mounted GIB was
      recorded. RESULTS: 77.2% of all GIBs were MF-mounted. 33.1% of mounted GIBs
      versus 48.8% of non-mounted GIBs were assessed as fully acceptable sections. The
      differences between these figures are not statistically significant. 41.7% of the
      mounted GIBs were placed with the mucosal surface facing the MF, which entails a
      risk of damaging the tissue. CONCLUSION: MF-mounting of GIB did not contribute to
      section quality. Since the handling of such specimens by the pathology lab
      technicians resulted in extra workload, this technique cannot be recommended in
      routine diagnostic work-up, as judged from a pathologist"s point of view.

PMID- 19758510
TI  - [Quality improvement in healthcare].
AB  - Quality improvement has been an important topic in Danish healthcare for the past
      20 years. Quality improvement in Denmark is based on Strategy for Quality
      Improvement in Health Care. A wide range of nationwide quality improvement
      projects have been initiated. From 2009 The Danish Health Care Quality Assessment
      Programme (the Accreditation Programme) will be implemented.

PMID- 19758511
TI  - [Vagoglossopharyngeal neuralgia treated with vascular decompression].
AB  - This case report describes a 63-year-old man referred with right-sided
      glossopharyngeal neuralgia. Magnetic resonance imaging (MRI) demonstrated
      asymmetry of the PICA vessels. A microvascular decompression was performed and
      complete remission of symptoms followed. After 14 months the neuralgia recurred,
      this time accompanied by sinus bradycardia/sinus arrest during attacks causing
      discomfort and syncopes. An MRI now demonstrated an arterial loop at the site of
      the vagoglossopharyngeal complex leaving the brainstem. After another
      microvascular decompression, complete remission of symptoms was observed.

PMID- 19758512
TI  - [Changing clinicians' prescription patterns].
AB  - In 2005 the Central Drug Committee in co-operation with the hospitals in the
      county of Copenhagen (H:S) focused on the increasing use of and expenditure
      derived from three tumour necrosis factor alpha (TNF-alpha) inhibitors. While the
      three inhibitors are estimated to be equivalent regarding efficacy and safety,
      eternacept and adalimumab are twice as expensive as infliximab. With a little
      effort, the Central Drug Committee succeeded in changing clinicians' prescription
      pattern in a cost-effective manner.

PMID- 19758513
TI  - [Missed stress fracture of the calcaneus].
AB  - A stress fracture of the calcaneus is the result of rhythmically recurring sub
      threshold traumata and is typically seen in athletes. The diagnosis is difficult
      because stress fractures are easily missed in traditional radiographs. It is
      therefore recommended to perform magnetic resonance imaging. Treatment includes
      paracetamol and rest - and in severe cases plaster bandage and/or walker. Stress
      fracture of the calcaneus should be considered in cases with acute onset of
      severe and persistent heel pain in physically active individuals.

PMID- 19758514
TI  - [Picture of the month: tinea capitis].

PMID- 19758515
TI  - Bipolar disorder: diagnostic conundrums and associated comorbidities.
AB  - Many patients with bipolar disorder are initially misdiagnosed. Clinicians may
      incorrectly diagnose bipolar disorder as unipolar depression, borderline
      personality disorder, schizophrenia, anxiety, or substance use disorder. The
      consequences of misdiagnosis can include intensified manic symptoms, reduced
      quality of life, and increased risk of suicide. To correctly diagnose patients
      with bipolar disorder, clinicians must be aware of associated comorbidities and
      methods of differentiating bipolar disorder from other illnesses.

PMID- 19758516
TI  - Medical monitoring in patients with bipolar disorder: clinical recommendations.
AB  - Treatments for bipolar disorder can increase the risk for thyroid dysfunction,
      weight gain, diabetes, and dyslipidemia. Because of these risks, a planned
      regimen of patient monitoring is recommended to track health concerns such as
      fluctuations in thyroid levels, weight, blood pressure, glucose levels, and lipid
      profile. Different health tests are needed depending on the type of medication
      the patient is prescribed.

PMID- 19758517
TI  - Practical lessons from effectiveness trials of care management and
      psychoeducation for bipolar disorder.
AB  - Bipolar disorder is a chronic condition with a tremendous economic burden, yet
      the majority of patients do not receive quality care. Organized treatment
      programs that employ features such as care coordinators and patient and family
      psychoeducation have been shown to improve clinical outcomes for patients with
      bipolar disorder. The implementation of organized care may also be a cost
      effective way to decrease bipolar symptoms and meet the individual patient's
      changing needs.

PMID- 19758518
TI  - Bipolar disorder and concurrent psychiatric and medical disorders.
AB  - A correct diagnosis of bipolar disorder is crucial to determining appropriate
      treatment strategies, but the majority of patients with this illness are
      initially misdiagnosed. Bipolar presentations share features with other
      psychiatric disorders such as unipolar depression and borderline personality
      disorder, and comorbid medical conditions further complicate diagnosis.
      Clinicians may minimize diagnostic and treatment issues by focusing on
      differential diagnosis and dual treatment of bipolar disorder and co-occurring
      conditions. The physical health of patients with bipolar disorder should be
      monitored, because this population is at risk for obesity, metabolic syndrome,
      and associated conditions.

PMID- 19758519
TI  - What have we learned about bipolar disorder from STEP-BD and other practical
      trials?
AB  - Certain developments are informing the treatment of patients with bipolar
      disorder. Results from the Systematic Treatment Enhancement Program for Bipolar
      Disorder (STEP-BD) study and other pragmatic clinical trials are providing
      practical information on relapse/recurrence, comorbidities, and pharmacologic and
      psychosocial treatment. Also, the Bipolar Trials Network (BTN) has been
      established to provide an infrastructure for National Institutes of Health (NIH)
      and trials with high public health significance. More research is needed to
      explore fundamental questions about bipolar disorder and its treatment.

PMID- 19758520
TI  - Antidepressant discontinuation and risk of suicide attempt: a retrospective,
      nested case-control study.
AB  - OBJECTIVE: Prior efforts to assess the impact of antidepressant use on risk of
      suicide attempt focused on antidepressant initiation or duration of use. Gaps
      remain in understanding risks associated with antidepressant discontinuation in
      the context of the drug regimen. We assessed the effects of antidepressant
      discontinuation on the risk of suicide attempt. METHOD: We report a nested case
      control study of suicide attempt with at least 12 months of prior observation. A
      retrospective cohort of 2.4 million patients with depression (ICD-9 codes 296.2,
      296.3, 300.4, and 311), aged 5-89 years, was created using standard Healthcare
      Effectiveness Data and Information Set (HEDIS) criteria; from this cohort, cases
      (n = 10,456) and controls (n = 41,815) were selected for study. Data were from a
      large, national, longitudinal, integrated claims database of managed care
      enrollees in the United States from calendar years 1999 through 2006. RESULTS:
      Compared to controls, cases were more likely to have used antidepressants, to
      have had multiple antidepressants, and to have had prior depressive episodes and
      inpatient stays that involved depression. After adjusting for confounding due to
      depression severity, comorbidities, and other medications, antidepressant use
      showed a protective effect for suicide attempt (OR = 0.62, P < .001). Compared to
      prior therapy, antidepressant discontinuation had a significant risk for suicide
      attempt (OR = 1.61, P < .05). Antidepressant initiation had the highest risk for
      suicide attempt (OR = 3.42, P < .05), followed by titration (titration up, OR =
      2.62; down, OR = 2.19; P < .05). CONCLUSIONS: Substantial confounding exists in
      examining the link between antidepressant use and suicide attempt, specifically
      regarding those factors associated with characteristics of depression.
      Antidepressant discontinuation showed a significant risk for suicide attempt, as
      did the period of an abbreviated trial, that is, stopping before a therapeutic
      regimen of 56 days had been reached. The highest risk was associated with
      initiation, a finding consistent with other studies, closely followed by periods
      of dosing changes and discontinuation. Patients should be closely monitored
      during these periods.

PMID- 19758521
TI  - Health benefit costs and absenteeism due to insomnia from the employer's
      perspective: a retrospective, case-control, database study.
AB  - OBJECTIVE: To objectively assess the economic impact of insomnia on direct
      medical and prescription costs and indirect absence-related salary replacement
      costs and on absences and to compare the prevalence and costs of comorbidities in
      employees with and without insomnia. METHOD: A retrospective analysis was
      performed on employee data from the Human Capital Management Services Research
      Reference Database (January 2001-September 2007). Employees were identified as
      having insomnia (ICD-9 criteria) based on history of receiving medications used
      to treat insomnia or physician's diagnosis of insomnia. Control employees had no
      history of medications used to treat insomnia and no insomnia diagnosis. Annual
      costs and number of absences were compared using 2-part regression models,
      controlling for demographics, job information, geographic region, comorbid
      disorders, and the Charlson Comorbidity Index score. Comorbidity prevalence,
      costs, and services were compared. RESULTS: Data were collected for 299,188
      employees (17,230 employees with insomnia and 281,958 control employees). Annual
      mean incremental costs were $2,053 greater (in total) for employees with insomnia
      compared with controls (specific increments: medical $751, drug $735, sick leave
      $208, short-term disability $179, long-term disability $10, and workers'
      compensation $170). Employees with insomnia missed a mean of 3.10 more workdays
      annually than those without insomnia. Nearly all comorbid conditions were more
      prevalent, were more costly, and resulted in a greater utilization of services in
      employees with insomnia compared to those without. All of the above comparisons
      were significant (P < .05). CONCLUSION: Insomnia was associated with increased
      costs, greater absenteeism, and an increased number of comorbid conditions in an
      employed population. Consistent with other analyses based on these data, the
      study estimated the annual cost of insomnia in the US civilian labor force to be
      approximately $15.0-17.7 billion (US dollars).

PMID- 19758522
TI  - Treatment of clozapine-induced hypersalivation with ipratropium bromide: a
      randomized, double-blind, placebo-controlled crossover study.
AB  - OBJECTIVE: Clozapine-induced hypersalivation (CIH) occurs in up to 57% of treated
      patients and can be the source of considerable subjective distress. Previous open
      label studies suggest that sublingual ipratropium bromide may be effective in
      treating CIH. METHOD: We conducted a randomized, double-blind, placebo-controlled
      crossover trial to evaluate the efficacy of ipratropium in 20 individuals with
      CIH between September 2006 and August 2007. This study was 5 to 6 weeks in
      duration, based on the participants' clozapine blood-monitoring schedule, and it
      consisted of two 2-week crossover phases separated by a 1- or 2-week washout
      period. Primary outcome measures included the reduction in the Toronto Nocturnal
      Hypersalivation Scale (TNHS) and the Clinical Global Impressions-Severity of
      Illness (CGI-S) and -Improvement (CGI-I) scales. Secondary outcomes included
      visual analog scales assessing hypersalivation severity (VAS-S) and distress (VAS
      D). RESULTS: No significant reduction in CIH was found on the TNHS (P = .379),
      CGI-S (P = .266), or CGI-I (P = .599). Moreover, no difference was noted between
      study groups on the VAS-S (P = .969) and VAS-D (P = .527). There was no
      difference in the number of CIH responders at the conclusion of the 2-week
      placebo (40%, n = 8) and ipratropium (45%, n = 9) study phases (45%, n = 9)
      according to the TNHS. Randomization order did not have a significant effect on
      TNHS, CGI-S, or CGI-I scores. Tolerability was comparable between groups, with
      dry mouth occurring in 1 placebo group subject and 2 ipratropium group subjects.
      CONCLUSIONS: Despite the reports of some preliminary studies that ipratropium is
      an efficacious treatment for CIH, ipratropium failed to demonstrate significant
      clinical effect in comparison to placebo. Further research should explore the
      efficacy of other locally acting anticholinergic agents or other classes of
      medications. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00381589.

PMID- 19758523
TI  - Neurocognitive dysfunctions in euthymic bipolar patients with and without prior
      history of alcohol use.
AB  - OBJECTIVE: Despite the additional complications associated with alcohol misuse in
      bipolar populations, it is generally the case that studies exploring
      neurocognitive aspects of bipolar disorder specifically exclude patients with
      alcohol abuse or dependence. Given the role of cognitive dysfunctions in overall
      illness outcome, this study addressed the neurocognitive functioning of patients
      with a history of alcohol abuse or dependence as compared to bipolar patients
      without such a history and healthy controls. METHOD: The study sample included
      100 subjects: 65 bipolar patients, 30 of whom with a history of alcohol abuse or
      dependence and 35 without a previous history of alcohol abuse or dependence,
      based on DSM-IV criteria, and a control group of 35 healthy subjects.
      Comprehensive neuropsychological tests were carried out during strictly defined
      clinical remission. Differences between groups were analyzed and a linear
      regression analysis was undertaken to establish predictors of psychosocial
      functioning as measured using the Global Assessment of Functioning. Data were
      collected from September 2006 to July 2007. RESULTS: Bipolar patients with a
      history of alcohol abuse or dependence obtained lower scores in the interference
      task of the Stroop test compared to the control group. Both patient groups showed
      a poorer performance in some verbal memory and executive function measures than
      healthy controls. Verbal learning impairment was significantly associated with
      poor psychosocial functioning. CONCLUSIONS: Cognitive dysfunctions appeared to be
      more strongly associated with bipolar disorder than with the "history of alcohol
      abuse or dependence" factor. Bipolar patients with history of alcohol misuse may
      have greater difficulties of inhibitory control, probably due to higher
      impulsivity.

PMID- 19758524
TI  - Assessing onset of treatment benefit in depression and anxiety: conceptual
      considerations.
AB  - OBJECTIVE: Methods for characterizing the onset of treatment benefit in major
      depressive disorder and generalized anxiety disorder have been studied for some
      time, yet there is no universal agreement as to the best approaches. Our purpose
      is to summarize the conceptual framework underlying modern methods for
      characterizing onset and detailed approaches for which there is consensus from
      the perspective of a clinician, clinical researcher, and statistician. Possible
      alternatives to unresolved issues are discussed. PARTICIPANTS: There were 17
      experts from academia, the pharmaceutical industry, and the US Food and Drug
      Administration who met on April 19, 2007, to consider the issues. Many others
      from sponsoring firms observed the proceedings. EVIDENCE: A series of papers was
      presented at a consensus meeting and, after discussions, a sense of the
      participants was obtained. A small group subsequently reviewed the material and
      articles from the literature and prepared this article, which was reviewed by all
      of the participants. CONCLUSIONS: The elements that form the basis for describing
      onset of treatment benefit include defining a clinical event or measurable
      threshold that validly signals that a treatment has begun to provide clinically
      meaningful and sustained improvement and utilizing methods for estimating the
      probability of crossing the onset threshold, the distribution of time to onset
      for those who do cross, and when to alter or change interventions if the
      treatment is unsuccessful.

PMID- 19758525
TI  - Trauma, emergency room visits, and cognition.

PMID- 19758526
TI  - Frequency and correlates of inappropriate pediatric psychiatric emergency room
      visits.
AB  - BACKGROUND: Despite increasing pediatric psychiatric emergency room service
      (PPERS) visits, data are lacking regarding visit characteristics and
      appropriateness. METHOD: This retrospective cohort study consecutively assessed
      youngsters aged < 18 years between January 1 and December 31, 2002, utilizing
      data from a 12-page semistructured institutional evaluation form.
      Appropriateness, severity, acuity, and harm potential of PPERS visits were rated
      on a Likert scale. RESULTS: Of 1,062 PPERS patient visits (mean +/- SD age: 13.5
      +/- 3.1 years, 51.1% male, and 51.2% white), 305 (28.7%) led to hospitalization.
      Although most patients (68.7%) were in outpatient care, only 21.9% sought and
      11.5% completed an outpatient evaluation prior to reaching the emergency room. As
      many as 34.4% of PPERS visits were somewhat/very inappropriate (optimal care:
      outpatient evaluation/treatment, even if delayed), 26.6% were somewhat
      appropriate/neutral (best served by outpatient evaluation/treatment, but timely
      appointment unavailable), and only 39.0% were fully appropriate. Main reasons for
      inappropriate PPERS visits were direct emergency room referral from school (P =
      .0056) or mental health provider (P = .0438) without prior psychiatrist
      evaluation, or unavailable appointment (P = .0304). Multivariate predictors of
      inappropriate PPERS visits (r(2) = .296, P < .0001) included current Global
      Assessment of Functioning score > 48 (P < .0001), absent suicidal
      ideation/attempt (P < .0001), low harm potential (< 4.4, P < .0001) and severity
      (< 4.8, P = .0136) (1- to 7-point scale) of presenting complaint, and absent
      psychosis (P = .0008). CONCLUSIONS: Over one third of PPERS visits were
      inappropriate, characterized by better functioning, low harm potential or
      severity of presenting complaint, and absent suicidality or psychosis.
      Development of and improved access to urgent child and adolescent psychiatric
      outpatient care services in the community and referral agent educational programs
      may minimize inappropriate PPERS visits.

PMID- 19758527
TI  - Genetic studies of drug response and side effects in the STAR*D study, part 1.

PMID- 19758528
TI  - Premature conclusions about psychotherapy for dysthymia.

PMID- 19758530
TI  - Overestimating the prevalence of subtherapeutic dosing of atypical
      antipsychotics.

PMID- 19758533
TI  - The importance of negative comorbidity.

PMID- 19758534
TI  - Selective serotonin reuptake inhibitor-induced spermatorrhea in 2 patients.

PMID- 19758536
TI  - Phenotypic expression of autoimmune autistic disorder (AAD): a major subset of
      autism.
AB  - BACKGROUND: Autism causes incapacitating neurologic problems in children that
      last a lifetime. The author of this article previously hypothesized that autism
      may be caused by autoimmunity to the brain, possibly triggered by a viral
      infection. This article is a summary of laboratory findings to date plus new data
      in support of an autoimmune pathogenesis for autism. METHODS: Autoimmune markers
      were analyzed in the sera of autistic and normal children, but the cerebrospinal
      fluid (CSF) of some autistic children was also analyzed. Laboratory procedures
      included enzyme-linked immunosorbent assay and protein immunoblotting assay.
      RESULTS: Autoimmunity was demonstrated by the presence of brain autoantibodies,
      abnormal viral serology, brain and viral antibodies in CSF, a positive
      correlation between brain autoantibodies and viral serology, elevated levels of
      proinflammatory cytokines and acute-phase reactants, and a positive response to
      immunotherapy. Many autistic children harbored brain myelin basic protein
      autoantibodies and elevated levels of antibodies to measles virus and measles
      mumps-rubella (MMR) vaccine. Measles might be etiologically linked to autism
      because measles and MMR antibodies (a viral marker) correlated positively to
      brain autoantibodies (an autoimmune marker)--salient features that characterize
      autoimmune pathology in autism. Autistic children also showed elevated levels of
      acute-phase reactants--a marker of systemic inflammation. CONCLUSIONS: The
      scientific evidence is quite credible for our autoimmune hypothesis, leading to
      the identification of autoimmune autistic disorder (AAD) as a major subset of
      autism. AAD can be identified by immune tests to determine immune problems before
      administering immunotherapy. The author has advanced a speculative
      neuroautoimmune (NAI) model for autism, in which virus-induced autoimmunity is a
      key player. The latter should be targeted by immunotherapy to help children with
      autism.

PMID- 19758537
TI  - Applied behavior analytic interventions for children with autism: a description
      and review of treatment research.
AB  - BACKGROUND: Autism is a disorder characterized by pervasive delays in the
      development of language and socialization, and the presence of stereotyped,
      repetitive behaviors or nonfunctional interests. Although a multitude of
      treatments for autism exist, very few have been the subject of scientific
      research. The only treatment that has been supported by substantial empirical
      research is treatment based on applied behavior analysis (ABA). METHODS: This
      article describes components of comprehensive ABA treatment programs, reviews
      research on effectiveness, and discusses issues related to collaboration between
      ABA and psychiatry. RESULTS: ABA has been supported by several hundred single
      case experiments and an increasing number of between-groups studies.
      Comprehensive ABA treatment programs are comprised of multiple intervention
      procedures, such as discrete trial instruction and natural environment training,
      and are founded on basic principles of learning and motivation, such as positive
      reinforcement, extinction, stimulus control, and generalization. Clinicians in
      the fields of ABA and psychiatry have similar goals regarding client outcome, and
      several ABA measurement and analysis procedures produce information that may be
      useful to psychiatrists. CONCLUSIONS: ABA treatment programs for individuals with
      autism are supported by a significant amount of scientific evidence and are
      therefore recommended for use. Patient care would likely benefit from a greater
      degree of collaboration between practitioners in the fields of ABA and
      psychiatry.

PMID- 19758535
TI  - The power and promise of identifying autism early: insights from the search for
      clinical and biological markers.
AB  - BACKGROUND: The biological changes that lead to autism likely occur during
      prenatal life. Although earlier identification of the disorder has occurred
      within the past decade, the mean age of diagnosis is still not made before a mean
      age of 3 years. This is because autism remains a behaviorally defined disorder,
      placing limits on the age at which a confident diagnosis can be made. The study
      of the biological basis of autism prior to age 3 is essential and can most
      directly be achieved with prospective research designs. METHODS: The literature
      on the early identification of autism is discussed, including the timescale for
      the onset of social symptoms. Also discussed is a new method for the prospective
      study of autism called the "1-Year Well-Baby Check-Up Approach," which allows for
      the prospective study of the disorder in simplex families with infants as young
      as 12 months of age. RESULTS: Although likely present at subtle, subclinical
      levels, early social abnormalities are not clearly detectable prior to 12 months
      in age in infants later diagnosed as having autism spectrum disorder.
      CONCLUSIONS: Using the 1-Year Well-Baby Check-Up Approach or other prospective
      design, examining early biomarkers related to early brain overgrowth, cerebellar
      development, gene expression patterns and immune system function may be key to
      early diagnosis efforts under 3 years. We also note the importance of comparing
      and contrasting the early "signature" of autism in children from singleton versus
      multiplex families, which may be etiologically distinct.

PMID- 19758538
TI  - Empowering families through Relationship Development Intervention: an important
      part of the biopsychosocial management of autism spectrum disorders.
AB  - BACKGROUND: Relationship Development Intervention (RDI) is a program designed to
      empower and guide parents of children, adolescents and young adults with autism
      spectrum disorders (ASD) and similar developmental disorders to function as
      facilitators for their children's mental development. RDI teaches parents to play
      an important role in improving critical emotional, social, and metacognitive
      abilities through carefully graduated, guided interaction in daily activities.
      METHODS: The paper reviews RDI's theoretical underpinnings, current methodology
      and preliminary research results. The clinical utilization of RDI is discussed as
      an important part of the biopsychosocial management of ASD. RESULTS: Although a
      controlled, blinded study of RDI has yet to be done, preliminary research
      suggests that parents, through the RDI curriculum and consultation process, have
      the potential to exert a powerful impact on their ASD children's experience
      sharing communication, social interaction, and adaptive functioning. CONCLUSIONS:
      RDI should be considered as part of a comprehensive treatment regimen, in which
      the physician plays a clinical management role, providing medical and psychiatric
      consultation. The RDI clinician can function as a remediation specialist,
      providing accurate feedback to the physician, along with individualized training
      and guidance to family members.

PMID- 19758540
TI  - Tuberculosis in a child - search for the infected adult nearby; case report,
      Portugal, 2007.
AB  - Tuberculosis (TB) transmission in a non-household setting is difficult to detect,
      because contact with the source case is often not obvious. Here, we report on a
      case of a four-year-old child who got infected through sporadic non-household
      exposure at a coffee shop. The source case was a woman who had suffered from
      weight loss, productive cough and fatigue for two months before being diagnosed
      with TB. Screening the child s contacts revealed two active TB cases within its
      family. Overall 148 contacts were screened for both cases and 18 cases of latent
      TB infection detected. The connection between the child and the source case, who
      were not aware of their contact, was confirmed by molecular fingerprinting. Our
      case report illustrates the difficulty in detecting non-household transmission
      between individuals that do not have significant contact, and draws attention to
      the need to look for the infected adult whenever a child falls ill with TB. This
      report is a reminder of the importance to consider possibly neglected ways of TB
      transmission and highlights once again the need of early diagnosis of TB.

PMID- 19758541
TI  - Detection of influenza A(H1N1)v virus by real-time RT-PCR.
AB  - Influenza A(H1N1)v virus was first identified in April 2009. A novel real-time RT
      PCR for influenza A(H1N1)v virus was set up ad hoc and validated following
      industry-standard criteria. The lower limit of detection of the assay was 384
      copies of viral RNA per ml of viral transport medium (95% confidence interval:
      273-876 RNA copies/ml). Specificity was 100% as assessed on a panel of reference
      samples including seasonal human influenza A virus H1N1 and H3N2, highly
      pathogenic avian influenza A virus H5N1 and porcine influenza A virus H1N1, H1N2
      and H3N2 samples. The real-time RT-PCR assay for the influenza A matrix gene
      recommended in 2007 by the World Health Organization was modified to work under
      the same reaction conditions as the influenza A(H1N1)v virus-specific test. Both
      assays were equally sensitive. Clinical applicability of both assays was
      demonstrated by screening of almost 2,000 suspected influenza (H1N1)v specimens,
      which included samples from the first cases of pandemic H1N1 influenza imported
      to Germany. Measuring influenza A(H1N1)v virus concentrations in 144 laboratory
      confirmed samples yielded a median of 4.6 log RNA copies/ml. The new methodology
      proved its principle and might assist public health laboratories in the upcoming
      influenza pandemic.

PMID- 19758542
TI  - Imported human African trypanosomiasis in Europe, 2005-2009.
AB  - Physicians in Europe are likely to see more African trypanosomiasis cases because
      of the increasing popularity of travel to Africa. In this paper the literature on
      imported cases in Europe, since 2005 is reviewed. Because of the high mortality
      risk associated with acute Rhodesian trypanosomiasis, travellers should be
      informed about preventive measures and the early disease manifestations.

PMID- 19758543
TI  - First identification of tick-borne encephalitis in Denmark outside of Bornholm,
      August 2009.
AB  - The incidence of tick-borne encephalitis (TBE) in Scandinavia is increasing and
      spreading geographically. Following two clinical cases of TBE hospitalised after
      tick bites in northern Zealand, Denmark, specific IgM and IgG antibodies against
      tick-borne encephalitis virus (TBEV) were demonstrated in acute serum samples of
      these patients. TBEV was identified by RT-PCR in ticks collected from the same
      location. This is the first report of TBEV in Ixodes ricinus leading to clinical
      cases in Denmark outside of Bornholm island.

PMID- 19758544
TI  - A neural network model of semantic memory linking feature-based object
      representation and words.
AB  - Recent theories in cognitive neuroscience suggest that semantic memory is a
      distributed process, which involves many cortical areas and is based on a
      multimodal representation of objects. The aim of this work is to extend a
      previous model of object representation to realize a semantic memory, in which
      sensory-motor representations of objects are linked with words. The model assumes
      that each object is described as a collection of features, coded in different
      cortical areas via a topological organization. Features in different objects are
      segmented via gamma-band synchronization of neural oscillators. The feature areas
      are further connected with a lexical area, devoted to the representation of
      words. Synapses among the feature areas, and among the lexical area and the
      feature areas are trained via a time-dependent Hebbian rule, during a period in
      which individual objects are presented together with the corresponding words.
      Simulation results demonstrate that, during the retrieval phase, the network can
      deal with the simultaneous presence of objects (from sensory-motor inputs) and
      words (from acoustic inputs), can correctly associate objects with words and
      segment objects even in the presence of incomplete information. Moreover, the
      network can realize some semantic links among words representing objects with
      shared features. These results support the idea that semantic memory can be
      described as an integrated process, whose content is retrieved by the co
      activation of different multimodal regions. In perspective, extended versions of
      this model may be used to test conceptual theories, and to provide a quantitative
      assessment of existing data (for instance concerning patients with neural
      deficits).

PMID- 19758545
TI  - Stochastic modeling of the transmission of respiratory syncytial virus (RSV) in
      the region of Valencia, Spain.
AB  - In this paper, we study the dynamics of the transmission of respiratory syncytial
      virus (RSV) in the population using stochastic models. The stochastic models are
      developed introducing stochastic perturbations on the demographic parameter as
      well as on the transmission rate of the RSV. Numerical simulations of the
      deterministic and stochastic models are performed in order to understand the
      effect of fluctuating birth rate and transmission rate of the RSV on the
      population dynamics. The numerical solutions of stochastic models are calculated
      using Euler-Maruyama and Milstein schemes, and confidence intervals for
      stochastic solutions are given using Monte-Carlo method. Analysis of the
      numerical results reveals that perturbations on the transmission rate are more
      decisive in the dynamics of RSV than perturbations on demographic parameters. In
      addition, the stochastic models show the advantage of reproducing more
      effectively the noisy RSV hospitalization data. It is concluded that these
      stochastic models are a viable option to provide a realistic modeling of the RSV
      dynamics on the population.

PMID- 19758546
TI  - Evolutionary games on networks and payoff invariance under replicator dynamics.
AB  - The commonly used accumulated payoff scheme is not invariant with respect to
      shifts of payoff values when applied locally in degree-inhomogeneous population
      structures. We propose a suitably modified payoff scheme and we show both
      formally and by numerical simulation, that it leaves the replicator dynamics
      invariant with respect to affine transformations of the game payoff matrix. We
      then show empirically that, using the modified payoff scheme, an interesting
      amount of cooperation can be reached in three paradigmatic non-cooperative two
      person games in populations that are structured according to graphs that have a
      marked degree inhomogeneity, similar to actual graphs found in society. The three
      games are the Prisoner's Dilemma, the Hawks-Doves and the Stag-Hunt. This
      confirms previous important observations that, under certain conditions,
      cooperation may emerge in such network-structured populations, even though
      standard replicator dynamics for mixing populations prescribes equilibria in
      which cooperation is totally absent in the Prisoner's Dilemma, and it is less
      widespread in the other two games.

PMID- 19758547
TI  - Implementation of a Hebbian chemoreceptor model for diffusive source
      localization.
AB  - While new approaches to chemical localization have been proposed, animals are
      still widely used for locating landmines and illegal substances. Existing
      electronic noses still do not have the necessary sensitivity and accuracy. By
      modeling a cell's chemical detection system, we can gain insight into the basic
      "olfactory" system. We use an inspiration from chemotaxis and Hebbian learning to
      enhance localization and tracking of gradient sources, which can be applied to
      both chemicals and heat. The eukaryotic receptor clustering model shows
      improvement over previous prokaryotic chemotaxis-inspired methods that do not
      take into account receptor clustering. Receptor clustering essentially adapts
      receptors spatio-temporally. For a mobile simulation, our method locates the
      source in less convergence time than the other chemotaxis algorithms and
      insignificantly less time compared to no spatio-temporal filtering (e.g. a single
      sensor memoryless case). We then show that local regions of receptor cooperation
      have the best performance reflecting observations of receptor behavior in
      biology. To demonstrate the performance of this system in real-time, a stationary
      4/8-sensor version of the array is implemented, and the algorithm improves the
      convergence time, mean, and variance of the Direction-of-Arrival calculation in
      diffusive, turbulent, and noisy environments.

PMID- 19758548
TI  - Self-organization in dissipative structures: a thermodynamic theory for the
      emergence of prebiotic cells and their epigenetic evolution.
AB  - This paper presents a discussion on self-organization processes in dissipative
      structures, in order to highlight the general conditions for raising complexity
      and generate order. In particular, some concepts were introduced from non
      equilibrium thermodynamics and from the Molecular Anamorphic Evolution Theory,
      especially concerning processes of matter randomization. Once a theoretical
      thermodynamics-based framework for understanding self-organizing systems had been
      presented, a spontaneous transition from macrostates richer in microstates to
      macrostates poorer in microstates was explained, as an attempt to point out the
      probable existing conditions at the formation of prebiotic structures. Closed
      systems, constrained by a lipid bilayer and with an internal water environment,
      were presented as cases of self-organization towards living systems. It was then
      highlighted that the origin of life depends on epigenetic and autopoietic
      processes, since metabolism plays a more relevant role than replication in making
      novelties emerge.

PMID- 19758549
TI  - Possibility of high performance quantum computation by superluminal evanescent
      photons in living systems.
AB  - Penrose and Hameroff have suggested that microtubules in living systems function
      as quantum computers by utilizing evanescent photons. On the basis of the theorem
      that the evanescent photon is a superluminal particle, the possibility of high
      performance computation in living systems has been studied. From the theoretical
      analysis, it is shown that the biological brain can achieve large quantum bits
      computation compared with the conventional processors at room temperature.

PMID- 19758550
TI  - Variable context Markov chains for HIV protease cleavage site prediction.
AB  - Deciphering the knowledge of HIV protease specificity and developing
      computational tools for detecting its cleavage sites in protein polypeptide chain
      are very desirable for designing efficient and specific chemical inhibitors to
      prevent acquired immunodeficiency syndrome. In this study, we developed a
      generative model based on a generalization of variable order Markov chains (VOMC)
      for peptide sequences and adapted the model for prediction of their cleavability
      by certain proteases. The new method, called variable context Markov chains
      (VCMC), attempts to identify the context equivalence based on the evolutionary
      similarities between individual amino acids. It was applied for HIV-1 protease
      cleavage site prediction problem and shown to outperform existing methods in
      terms of prediction accuracy on a common dataset. In general, the method is a
      promising tool for prediction of cleavage sites of all proteases and encouraged
      to be used for any kind of peptide classification problem as well.

PMID- 19758551
TI  - Creating abstract topographic representations: implications for coding, learning
      and reasoning.
AB  - Topographic maps are a fundamental and ubiquitous feature of the sensory and
      motor regions of the brain. There is less evidence for the existence of
      conventional topographic maps in associational areas of the brain such as the
      prefrontal cortex and parietal cortex. The existence of topographically arranged
      anatomical projections is far more widespread and occurs in associational regions
      of the brain as well as sensory and motor regions: this points to a more
      widespread existence of topographically organised maps within associational
      cortex than currently recognised. Indeed, there is increasing evidence that
      abstract topographic representations may also occur in these regions. For
      example, a topographic mnemonic map of visual space has been described in the
      dorsolateral prefrontal cortex and topographically arranged visuospatial
      attentional signals have been described in parietal association cortex. This
      article explores how abstract representations might be extracted from sensory
      topographic representations and subsequently code abstract information. Finally a
      simple model is presented that shows how abstract topographic representations
      could be integrated with other information within the brain to solve problems or
      form abstract associations. The model uses correlative firing to detect
      associations between different types of stimuli. It is flexible because it can
      produce correlations between information represented in a topographic or non
      topographic coordinate system. It is proposed that a similar process could be
      used in high-level cognitive operations such as learning and reasoning.

PMID- 19758552
TI  - The curious case of bivalent marks.
AB  - Bivalently marked chromatin, containing both histone H3 lysine 4 (H3K4) and H3K27
      trimethylation, is a hallmark of developmentally regulated paused promoters in
      mammalian embryonic stem cells. In this issue of Developmental Cell, Akkers et
      al. report that Xenopus tropicalis embryos transition through early development
      without the requirement for bivalently marked promoters.

PMID- 19758553
TI  - Shugoshin and PP2A: collaborating to keep chromosomes connected.
AB  - Timely release of sister chromatid cohesion is essential for accurate chromosome
      segregation during cell division. Shugoshin forms a complex with the phosphatase
      PP2A that has been proposed to dephosphorylate cohesin proteins to prevent
      premature loss of centromeric cohesion. A recent study in Molecular Cell by Xu et
      al. presents the structure of Shugoshin bound to PP2A and provides evidence that
      this interaction is required for cohesion protection.

PMID- 19758554
TI  - Orchestrating twosome and foursome chromosome parties.
AB  - The conserved centromere protein C (CENP-C) is indispensable for kinetochore
      function. Yet its mechanism of action has remained elusive. In this issue of
      Developmental Cell, Tanaka et al. report that the fission yeast homolog, Cnp3,
      acts as a linker protein that fulfills a variety of different roles in the bi-
      and mono-orientation of chromosomes during mitosis and meiosis I.

PMID- 19758555
TI  - Mechanisms of cellular protrusions branch out.
AB  - F-BAR domains bind curved membranes and induce membrane invagination. In a recent
      Cell paper, Guerrier et al. describe an "inverse" F-BAR family member that
      induces outward curvature and filopodia in migrating neurons. These findings
      suggest that F-BAR domains are functionally diverse and regulate different types
      of membrane morphology.

PMID- 19758556
TI  - Actin dynamics at the leading edge: from simple machinery to complex networks.
AB  - Cell migration is an essential feature of eukaryotic life, required for processes
      ranging from feeding and phagoctyosis to development, healing, and immunity.
      Migration requires the actin cytoskeleton, specifically the localized
      polymerization of actin filaments underneath the plasma membrane. Here we
      summarize recent developments in actin biology that particularly affect
      structures at the leading edge of the cell, including the structure of actin
      branches, the multiple pathways that lead to cytoskeleton assembly and
      disassembly, and the role of blebs. Future progress depends on connecting these
      processes and components to the dynamic behavior of the whole cell in three
      dimensions.

PMID- 19758557
TI  - CLIP-170-dependent capture of membrane organelles by microtubules initiates minus
      end directed transport.
AB  - Cytoplasmic microtubules (MTs) continuously grow and shorten at free plus ends.
      During mitosis, this dynamic behavior allows MTs to capture chromosomes to
      initiate their movement to the spindle poles; however, the role of MT dynamics in
      capturing organelles for transport in interphase cells has not been demonstrated.
      Here we use Xenopus melanophores to test the hypothesis that MT dynamics
      significantly contribute to the efficiency of MT minus-end directed transport of
      membrane organelles. We demonstrate that initiation of transport of membrane
      bounded melanosomes (pigment granules) to the cell center involves their capture
      by MT plus ends, and that inhibition of MT dynamics or loss of the MT plus-end
      tracking protein CLIP-170 from MT tips dramatically inhibits pigment aggregation.
      We conclude that MT dynamics are required for the initiation of MT transport of
      membrane organelles in interphase cells, and that +TIPs such as CLIP-170 play an
      important role in this process.

PMID- 19758558
TI  - CENP-C functions as a scaffold for effectors with essential kinetochore functions
      in mitosis and meiosis.
AB  - The conserved kinetochore protein CENP-C plays a fundamental role in chromosome
      segregation, but its specific functions remain elusive. We have gained insights
      into the role of CENP-C through identification of interacting effector proteins
      required for kinetochore function in fission yeast. Fta1/CENP-L is a primary
      effector that associates directly with Cnp3/CENP-C, and ectopic localization of
      Fta1 largely suppresses the mitotic kinetochore defects of cnp3Delta cells. Pcs1
      functions downstream of Cnp3 to prevent merotelic attachment. In meiosis, Cnp3
      further associates with and recruits Moa1, a meiosis-specific protein exclusively
      required for the mono-orientation of kinetochores. Genetic and biochemical
      analyses identified Cnp3 mutants that preserve intact mitotic kinetochore
      function but abolish the association with Moa1 and meiotic mono-orientation.
      Overall, therefore, our studies identify effectors of CENP-C in mitosis and
      meiosis and establish the concept that CENP-C serves as a scaffold for the
      specific recruitment of essential kinetochore proteins.

PMID- 19758559
TI  - Polo kinase and separase regulate the mitotic licensing of centriole duplication
      in human cells.
AB  - It has been proposed that separase-dependent centriole disengagement at anaphase
      licenses centrosomes for duplication in the next cell cycle. Here we test whether
      such a mechanism exists in intact human cells. Loss of separase blocked centriole
      disengagement during mitotic exit and delayed assembly of new centrioles during
      the following S phase; however, most engagements were eventually dissolved. We
      identified Polo-like kinase 1 (Plk1) as a parallel activator of centriole
      disengagement. Timed inhibition of Plk1 mapped its critical period of action to
      late G2 or early M phase, i.e., prior to securin destruction and separase
      activation at anaphase onset. Crucially, when cells exited mitosis after
      downregulation of both separase and Plk1, centriole disengagement failed
      completely, and subsequent centriole duplication in interphase was also blocked.
      Our results indicate that Plk1 and separase act at different times during M phase
      to license centrosome duplication, reminiscent of their roles in removing cohesin
      from chromosomes.

PMID- 19758560
TI  - Translational repression of cyclin E prevents precocious mitosis and embryonic
      gene activation during C. elegans meiosis.
AB  - Germ cells, the cells that give rise to sperm and egg, maintain the potential to
      recreate all cell types in a new individual. This wide developmental potential,
      or totipotency, is manifested in unusual tumors called teratomas, in which germ
      cells undergo somatic differentiation. Although recent studies have implicated
      RNA regulation, the mechanism that normally prevents the loss of germ cell
      identity remains unexplained. In C. elegans, a teratoma is induced in the absence
      of the conserved RNA-binding protein GLD-1. Here, we demonstrate that GLD-1
      represses translation of CYE-1/cyclin E during meiotic prophase, which prevents
      germ cells from re-entering mitosis and inducing embryonic-like transcription. We
      describe a mechanism that prevents precocious mitosis in germ cells undergoing
      meiosis, propose that this mechanism maintains germ cell identity by delaying the
      onset of embryonic gene activation until after fertilization, and provide a
      paradigm for the possible origin of human teratomas.

PMID- 19758561
TI  - Redefining the progression of lineage segregations during mammalian embryogenesis
      by clonal analysis.
AB  - Clonal lineage information is fundamental in revealing cell fate choices. Using
      genetic single-cell labeling in utero, we investigated lineage segregations
      during anteroposterior axis formation in mouse. We show that while endoderm and
      surface ectoderm segregate during gastrulation, neural ectoderm and mesoderm
      share a common progenitor persisting through all stages of axis elongation. These
      data challenge the paradigm that the three germ layers, formed by gastrulation,
      constitute the primary branchpoints in differentiation of the pluripotent
      epiblast toward tissue-specific precursors. Bipotent neuromesodermal progenitors
      show self-renewing characteristics and may represent the cellular substrate
      coupling sustained axial elongation and coordinated differentiation of these
      tissues. These findings have important implications for the interpretation of the
      phenotypic defects of several mouse mutants and the directed differentiation of
      embryonic stem (ES) cells in vitro.

PMID- 19758562
TI  - Local guidance of emerging vessel sprouts requires soluble Flt-1.
AB  - Blood vessel networks form via sprouting of endothelial cells from parent
      vessels. Extrinsic cues guide sprouts after they leave the initiation site, but
      these cues are likely insufficient to regulate initial outward movement, and many
      embryonic vessel networks form in the absence of a strong extrinsic gradient. We
      hypothesized that nascent sprouts are guided by spatial cues produced along their
      own vessels, and that soluble Flt-1 (sFlt-1) participates in this guidance.
      Analysis of developing vessels with perturbed flt-1 function revealed misguided
      emerging sprouts, and transgenic sFlt-1 rescued sprout guidance parameters. sflt
      1 activity in endothelial cells immediately adjacent to the emerging sprout
      significantly improved local sprout guidance. Thus, we propose that a vessel
      intrinsic system initially guides emerging sprouts away from the parent vessel,
      utilizing spatially regulated expression of sFlt-1 in conjunction with exogenous
      VEGF-A. Local sprout guidance defects are predicted to contribute to vessel
      dysmorphogenesis during perturbed development and disease.

PMID- 19758563
TI  - The vacuolar proton pump, V-ATPase, is required for notch signaling and endosomal
      trafficking in Drosophila.
AB  - We have identified Rabconnectin-3alpha and beta (Rbcn-3A and B) as two regulators
      of Notch signaling in Drosophila. We found that, in addition to disrupting Notch
      signaling, mutations in Rbcn-3A and B cause defects in endocytic trafficking,
      where Notch and other membrane proteins accumulate in late endosomal
      compartments. We show that Notch is transported to the surface of mutant cells
      and that signaling is disrupted after the S2 cleavage. Interestingly, the yeast
      homolog of Rbcn-3A, Rav1, regulates the V-ATPase proton pump responsible for
      acidifying intracellular organelles. We found that, similarly, Rbcn-3A and B
      appear to regulate V-ATPase function. Moreover, we identified mutants in VhaAC39,
      a V-ATPase subunit, and showed that they phenocopy Rbcn-3A and Rbcn-3B mutants.
      Our results demonstrate that Rbcn-3 affects Notch signaling and trafficking
      through regulating V-ATPase function, which implies that the acidification of an
      intracellular compartment in the receiving cells is crucial for signaling.

PMID- 19758564
TI  - A link between ER tethering and COP-I vesicle uncoating.
AB  - The yeast Dsl1p vesicle tethering complex, comprising the three subunits Dsl1p,
      Dsl3p, and Tip20p, is stably associated with three endoplasmic reticulum
      localized Q-SNAREs and is believed to play a central role in the tethering and
      fusion of Golgi-derived COP-I transport vesicles. Dsl1p also interacts directly
      with COP-I subunits. We now show that binding of Dsl1p to COP-I subunits involves
      binding sites identical to those involved in interactions between COP-I subunits
      that stabilize the COP-I coat. Cells with defects in Dsl/SNARE complex function
      show massive accumulation of COP-I-coated vesicles in a cluster to which COP-II
      coat proteins are also recruited. Our results suggest that binding of Dsl/SNARE
      complex to the COP-I coat complex serves two functions: to mediate vesicle
      tethering and to assist the uncoating process by blocking domains in COP-I that
      drive repolymerization and the formation of large COP-I aggregates.

PMID- 19758565
TI  - Drosophila maelstrom ensures proper germline stem cell lineage differentiation by
      repressing microRNA-7.
AB  - Nuage is a germline-unique perinuclear structure conserved throughout the animal
      kingdom. Maelstrom (Mael) is an unusual nuage component, as it is also found in
      the nucleus. Mael contains a High Mobility Group box, known to mediate DNA
      binding. We show that Mael nuclear function is required for proper
      differentiation in the Drosophila germline stem cell (GSC) lineage. In mael
      mutant testes, transit-amplifying cysts fail to differentiate into primary
      spermatocytes, instead breaking down into ectopic GSCs and smaller cysts, due to
      a depletion of Bag-of-marbles (Bam) protein. Mael regulates Bam via repression of
      miR-7. Mael binds the miR-7 promoter and is required for the local accumulation
      of HP1 and H3K9me3. miR-7 targets bam directly at its 3'UTR, and a reduction in
      miR-7 expression can rescue germline differentiation defects found in mael
      mutants by alleviating Bam repression. We propose that Mael ensures proper
      differentiation in the GSC lineage by repressing miR-7.

PMID- 19758566
TI  - A hierarchy of H3K4me3 and H3K27me3 acquisition in spatial gene regulation in
      Xenopus embryos.
AB  - Epigenetic mechanisms set apart the active and inactive regions in the genome of
      multicellular organisms to produce distinct cell fates during embryogenesis.
      Here, we report on the epigenetic and transcriptome genome-wide maps of gastrula
      stage Xenopus tropicalis embryos using massive parallel sequencing of cDNA (RNA
      seq) and DNA obtained by chromatin immunoprecipitation (ChIP-seq) of histone H3
      K4 and K27 trimethylation and RNA Polymerase II (RNAPII). These maps identify
      promoters and transcribed regions. Strikingly, genomic regions featuring opposing
      histone modifications are mostly transcribed, reflecting spatially regulated
      expression rather than bivalency as determined by expression profile analyses,
      sequential ChIP, and ChIP-seq on dissected embryos. Spatial differences in
      H3K27me3 deposition are predictive of localized gene expression. Moreover, the
      appearance of H3K4me3 coincides with zygotic gene activation, whereas H3K27me3 is
      predominantly deposited upon subsequent spatial restriction or repression of
      transcriptional regulators. These results reveal a hierarchy in the spatial
      control of zygotic gene activation.

PMID- 19758567
TI  - Genetic polymorphism of interleukin-16 and risk of nasopharyngeal carcinoma.
AB  - BACKGROUND: Common genetic variants in inflammatory cytokine genes can affect the
      risk of developing nasopharyngeal carcinoma (NPC). Interleukin-16 (IL-16), a pro
      inflammatory cytokine, plays a pivotal role in inflammatory diseases as well as
      in the pathogenesis of tumors. METHODS: We analyzed rs4778889 T/C, rs11556218
      T/G, and rs4072111 C/T polymorphisms of IL-16 in 206 patients with NPC and 373
      healthy controls in a Chinese population, using a polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) strategy and DNA sequencing
      methods. RESULTS: The rs11556218 T/G polymorphism of IL-16 gene was significantly
      associated with the susceptibility to NPC. The TG genotype was associated with a
      significantly higher risk of NPC as compared with the TT genotype (OR=1.67; 95%
      CI, 1.18-2.36). Patients carrying the G allele had a significantly higher risk
      for developing NPC compared to individuals carrying the T allele (OR=1.36; 95%
      CI, 1.03-1.78). CONCLUSIONS: This study shows an association between IL-16 gene
      polymorphisms and the risk of NPC, and our data suggests that IL-16 gene
      polymorphisms may be useful as genetic susceptibility markers for NPC.

PMID- 19758568
TI  - Pre-analytical factors that influence the interpretation of prothrombin time in
      the clinical laboratory: one year experience in a super speciality hospital in
      India.
AB  - BACKGROUND: Accuracy and precision of Laboratory results is a top most priority
      in a clinical laboratory. Errors in Laboratory results could be due to pre
      analytical, analytical and postanalytical variables. Here, we have discussed
      about pre-analytical variables during estimation of prothrombin time. METHODS:
      15,335 PT (prothrombin time) samples received in the department of clinical
      biochemistry from June 2008 to May 2009 were evaluated for the prevalence of pre
      analytical errors. The prothrombin time (PT) was analyzed on automated
      coagulometer-ACL 7000 with thromboplastin reagent supplied by Trinity Biotech,
      Ireland. RESULTS: Out of the 15,335 samples received in one year for analysis by
      the department, 464 samples showed the presence of pre-analytical variables and
      therefore, could not be assayed. Among the pre-analytical variables,
      inappropriate proportion between blood and anticoagulant was the most common
      error with a frequency of approximately 60%. Clotted samples and illegible
      handwriting accounted for another 15% each of the rejections respectively. Around
      6% of the samples were hemolysed and another 2% were rejected due to lipemia.
      CONCLUSION: Appropriate knowledge of blood sample collection is a need of an hour
      to have accuracy in Laboratory results.

PMID- 19758569
TI  - Genetic polymorphism of the tissue inhibitor of metalloproteinase-1 is associated
      with an increased risk of endometrial cancer.
AB  - BACKGROUND: Tissue inhibitors of metalloproteinases (TIMPs) are a family of
      multifunctional proteins known to possess a broad range of biological activities
      involved in tumorgenesis and mRNA expression of TIMP family members has been
      shown to be upregulated in numerous cancers and correlates with clinical
      outcomes. We investigated the association of TIMP-1 and TIMP-2 gene polymorphism
      with risk of endometrial cancer. METHODS: In the present case-control study, we
      enrolled a total of 118 endometrial cancer patients confirmed by histopathology
      and 229 unrelated healthy individuals. Polymorphism for TIMP-1 (_372C>T) and TIMP
      2 (_418G>C and _303C>T) genes was genotyped by PCR-RFLP. RESULTS: Frequency of
      TIMP-1_372C/C genotype and 372-C allele differed significantly between patients
      with endometrial cancer (38.1% and 56.4% respectively) and healthy individuals
      (22.7% and 44.1% respectively). Individuals with TIMP-1_372 C/C genotype were at
      higher risk of endometrial cancer (OR=2.37; 95%CI: 1.33-4.22). Stratification
      analysis showed that individuals with TIMP-1_372 C/C genotype were at increased
      risk for endometrioid (OR=2.46; 95% CI 1.34-4.53) and low stage (stages I-II)
      endometrial cancer (OR=3.24; 95% CI 1.22-4.13). However, no significant
      differences in TIMP-2_418G>C and TIMP-2_303C>T genotypes were observed between
      endometrial carcinoma cases and controls. CONCLUSION: Individuals with TIMP
      1_372C/C genotype were at significantly higher risk of endometrial cancer.

PMID- 19758571
TI  - Environmental causes of violence.
AB  - Violent and anti-social behavior is usually attributed to social factors,
      including poverty, poor education, and family instability. There is also evidence
      that many forms of violent behavior are more frequent in individuals of lower IQ.
      The role of exposure to environmental contaminants has received little attention
      as a factor predisposing to violent behavior. However a number of environmental
      exposures are documented to result in a common pattern of neurobehavioral
      effects, including lowered IQ, shortened attention span, and increased frequency
      of antisocial behavior. This pattern is best described for children exposed to
      lead early in life, but a similar pattern is seen upon exposure to
      polychlorinated biphenyls and methyl mercury. Although not as extensively
      studied, similar decrements in IQ are seen upon exposure to arsenic and
      secondhand smoke (SHS) exposure. Prenatal and postnatal SHS exposure is also
      associated with increased rates of conduct disorder and attention deficit
      hyperactivity. Recent evidence suggests that temporal trends in rates of violent
      crime in many nations are consistent with earlier preschool blood lead trends,
      with a lag of about 20 years. These ecologic correlations are consistent with
      many controlled studies suggesting that lead-exposed children suffer irreversible
      brain alterations that make them more likely to commit violent crimes as young
      adults. If this pattern is true for lead and other contaminants, the most
      effective way to fight crime may be to prevent exposure to these contaminants.

PMID- 19758570
TI  - Estrogen rapidly attenuates cannabinoid-induced changes in energy homeostasis.
AB  - We examined whether estrogen negatively modulates cannabinoid-induced regulation
      of food intake, core body temperature and neurotransmission at
      proopiomelanocortin (POMC) synapses. Food intake was evaluated in ovariectomized
      female guinea pigs abdominally implanted with thermal DataLoggers and treated
      s.c. with the cannabinoid CB(1)/CB(2) receptor agonist WIN 55,212-2, the CB(1)
      receptor antagonist AM251 or their cremephor/ethanol/0.9% saline vehicle, and
      with estradiol benzoate (EB) or its sesame oil vehicle. Whole-cell patch clamp
      recordings were performed in slices through the arcuate nucleus. WIN 55,212-2
      produced dose- and time-dependent increases in food intake. EB decreased food
      intake 8-24h after administration, but rapidly and completely blocked the
      increase in consumption caused by WIN 55,212-2. EB also attenuated the WIN 55,212
      2-induced decrease in core body temperature. The AM251-induced decrease in food
      intake was unaffected. The diminution of the WIN 55,212-2-induced increase in
      food intake caused by EB correlated with a marked attenuation of cannabinoid
      receptor-mediated decreases in glutamatergic miniature excitatory postsynaptic
      current frequency occurring within 10-15min of steroid application. Furthermore,
      EB completely blocked the depolarizing shift in the inactivation curve for the A
      type K(+) current caused by WIN 55,212-2. The EB-mediated, physiologic antagonism
      of these presynaptic and postsynaptic actions elicited upon cannabinoid receptor
      activation was observed in arcuate neurons immunopositive for phenotypic markers
      of POMC neurons. These data reveal that estrogens negatively modulate cannabinoid
      induced changes in appetite, body temperature and POMC neuronal activity. They
      also impart insight into the neuroanatomical substrates and effector systems upon
      which these counter-regulatory factors converge in the control of energy
      homeostasis.

PMID- 19758572
TI  - Ultrasonic communication in rats: effects of morphine and naloxone on vocal and
      behavioral responses to playback of 50-kHz vocalizations.
AB  - Rats emit ultrasonic vocalizations and it was hypothesized that these
      vocalizations have an important role in intra-specific communication. Recently,
      we demonstrated that playback of 50-kHz ultrasonic vocalizations can induce
      social approach, indicating that 50-kHz calls can serve to (re)establish or to
      maintain social contact. It is known that endogenous opioids are implicated in
      the regulation of social behavior, particularly in rough and tumble play. Here,
      we tested whether administration of opioid ligands can affect social approach in
      response to playback of 50-kHz calls in juvenile and adult rats. Rats were either
      treated with 1mg/kg naloxone, 1mg/kg morphine, or with saline vehicle.
      Administration of opioid ligands affected social approach at both ages.
      Specifically, in juvenile and adult rats, social approach displayed in response
      to playback of 50-kHz calls was reduced in case of naloxone treatment, but
      enhanced with morphine. Furthermore, juvenile rats treated with saline or
      morphine emitted a substantial amount of ultrasonic vocalizations in response to
      the playback of 50-kHz calls. Such ultrasonic calling was not seen in naloxone
      treated rats. Importantly, these drug-dependent differences were stimulus
      specific, i.e. seen only in response to playback of 50-kHz calls and not in
      response to playback of background noise. The present finding that opioid ligands
      can affect social approach and ultrasonic vocalizations induced by playback of 50
      kHz calls, indicates that an important feature of social interaction in rats,
      namely ultrasonic communication, is at least partially regulated by endogenous
      opioids.

PMID- 19758573
TI  - Target specific and long-acting delivery of protein, peptide, and nucleotide
      therapeutics using hyaluronic acid derivatives.
AB  - Hyaluronic acid (HA) is a biodegradable, biocompatible, non-toxic, non
      immunogenic and non-inflammatory linear polysaccharide, which has been used for
      various medical applications such as arthritis treatment, ocular surgery, tissue
      augmentation, and so on. In this review, the effect of chemical modification of
      HA on its distribution throughout the body was reported for target specific and
      long-acting delivery applications of protein, peptide, and nucleotide
      therapeutics. According to the real-time bio-imaging of HA derivatives using
      quantum dots (QDot), HA-QDot conjugates with 35mol% HA modification maintaining
      enough binding sites for HA receptors were mainly accumulated in the liver, while
      those with 68mol% HA modification losing much of HA characteristics were evenly
      distributed to the tissues in the body. The results are well matched with the
      fact that HA receptors are abundantly present in the liver with a high
      specificity to HA molecules. Accordingly, slightly modified HA derivatives were
      used for target specific intracellular delivery of nucleotide therapeutics and
      highly modified HA derivatives were used for long-acting conjugation of peptide
      and protein therapeutics. HA has been also used as a novel depot system in the
      forms of physically and chemically crosslinked hydrogels for various protein drug
      delivery. This review will give you a peer overview on novel HA derivatives and
      the latest advances in HA-based drug delivery systems of various
      biopharmaceuticals for further clinical development.

PMID- 19758575
TI  - Adjunctive quetiapine may help depression comorbid with pervasive developmental
      disorders.

PMID- 19758574
TI  - Micro- and nanotechnologies for intelligent and responsive biomaterial-based
      medical systems.
AB  - Advances in medical treatments of a wide variety of pathophysiological conditions
      require the development of better therapeutic agents, as well as a combination of
      the required therapeutic agents with device-integrated biomaterials that can
      serve as sensors and carriers. Combination of micro- and nano-fabricated systems
      with intelligent biomaterials that have the ability to sense and respond is a
      promising avenue for the development of better diagnostic and therapeutic medical
      systems. Micro- and nano-electromechanical systems (MEMs and NEMs) are now
      becoming a family of potentially powerful new technologies for drug delivery,
      diagnostic tools, and tissue engineering. Improvements in micro- and nano
      fabrication technologies have enhanced the ability to create better performing
      therapeutic systems for numerous pathophysiological applications. More
      importantly, MEMS- and NEMS-based tissue regeneration scaffolds, biosensors, and
      drug delivery devices provide new opportunities to mimic the natural intelligence
      and response of biological systems.

PMID- 19758576
TI  - The presence and quantification of splenic ice in the McMurdo Sound notothenioid
      fish, Pagothenia borchgrevinki (Boulenger, 1902).
AB  - Survival of some polar fishes is associated with high levels of circulating
      antifreeze glycoproteins (AFGPs). AFGP prevent ice growth giving rise to thermal
      hysteresis. The inhibiting action of AFGPs implies that polar fish contain ice to
      which AFGPs adsorb. Cryopelagic Pagothenia borchgrevinki, inhabiting the ice
      laden waters of McMurdo Sound, Antarctica, were assayed for ice and ice was found
      on skin, gills, in the intestine, and in the spleen. Two methods used to assess
      the number of ice crystals in spleens gave comparable results (12.1+/-1.9 and
      22+/-3.8 per spleen). Attempts were made to measure the rate of uptake of ice by
      P. borchgrevinki held in cages immediately beneath the sub-ice platelet layer in
      McMurdo Sound; uptake was sporadic. Introduction of ice into fish by spray
      freezing a small patch of the integument resulted in detection of splenic ice
      after 1h, illustrating that a mechanism exists for ice transport from the
      periphery to the spleen. Splenic ice did not seem to be eliminated from fish held
      in ice-free water at -1.6 degrees C for approximately two months. The relatively
      small number of splenic ice crystals and the slow rate of ice uptake suggest
      efficient ice barriers exist in P. borchgrevinki.

PMID- 19758577
TI  - The absorption efficiency and respiration rate of the Florida lancelet,
      Branchiostoma floridae.
AB  - The present study investigates some aspects of the digestive biology and
      physiological energetics of the Florida lancelet, Branchiostoma floridae. Florida
      lancelets are able to remove 47.2-56.9% of the energy from a diet of mixed algae.
      The respiration rate is 0.100mL O(2) (STPD) h(-1) g(-1) (wet), which estimates a
      metabolic rate of 0.248 J h(-1), at an average body mass of 0.125 g (wet).
      Published values of the chlorophyll a concentration in its natural habitat
      indicate that a 125 mg lancelet would need to filter 0.018-0.031 L h(-1) to
      remove sufficient food to support its resting metabolism. The filtration rate of
      lancelets has been reported as 0.138 L h(-1), indicating that the actual
      filtration rate is 4-7 times greater than the filtration rate needed to meet
      resting metabolic demands. It appears that lancelets have the potential to be
      raised in aquaculture, because their absorption efficiency and respiration rate
      are comparable to suspension-feeding invertebrates that have been successfully
      aquacultured.

PMID- 19758578
TI  - Identification of mitochondrial cytochrome P450 induced in response to polycyclic
      aromatic hydrocarbons in the mummichog (Fundulus heteroclitus).
AB  - Increasing evidence suggests that polycyclic aromatic hydrocarbons (PAHs) such as
      benzo[a]pyrene (BaP) are localized to the mitochondria. Because the toxic effects
      of many PAHs are the result of metabolism by cytochrome P4501A (CYP1A), it is
      important to investigate whether active forms of these enzymes can be identified
      in the mitochondria. In this study, we identified mitochondrial P450s with a
      monoclonal antibody against scup (Stenotomus chrysops) CYP1A in the isolated
      mitochondrial fraction of the liver from adult male mummichog (Fundulus
      heteroclitus) livers. The size of the protein in the mitochondria was similar to
      that of microsomal CYP1A. Fish dosed with 10mg/kg BaP had increased EROD activity
      in the mitochondrial fraction compared to controls. In mummichog larvae dosed
      with 100 microg/L BaP and 100 microg/L benzo[k]fluoranthene, CYP1A protein levels
      as well as enzyme activity were elevated. However, fish from a PAH-polluted
      Superfund site (Elizabeth River, Portsmouth VA) showed recalcitrant mitochondrial
      CYP1A protein levels and enzyme activity in a similar manner to microsomal CYP1A.

PMID- 19758579
TI  - Disappointment and drop-out rate after being allocated to control group in a
      smoking cessation trial.
AB  - BACKGROUND: If a patient agrees to take part in a randomised trial it is
      reasonable to presume that the patient would prefer to be allocated into the
      intervention. This study's aim was to investigate how patients react after they
      have been randomised into control group. METHODS: Nested study within two
      randomised trials. Telephone interviews with a structured questionnaire. The
      participants were invited after they had been randomised into the control group
      in two smoking cessation trials. The main outcome measures were reaction to
      control group allocation and drop-out rates. RESULTS: Twenty-seven out of 30
      possible interviews were successfully completed. Fourteen persons expressed that
      they were disappointed of being allocated to the control group. Five persons said
      that they had not understood the consent information and three of these were very
      disappointed. Surprisingly these three persons said that they had not expected a
      randomization. A woman expressed that she "felt as if I was being swindled".
      There were in total 9/117 (7.7%) lost to follow-up in the control group and there
      were 4/105 (3.8%) losses to follow-up in the intervention group (P=0.26). Active
      withdrawal of consent was slightly higher among the control group, five in the
      control group (4.3%) and no active withdrawals in the intervention group
      (P=0.06). CONCLUSIONS: Disappointment was common after allocation to the control
      group. This is a probable explanation of the higher drop-out rate in the control
      group. The consent information is of highest importance since those who were very
      disappointed claimed they did not receive understandable information.

PMID- 19758580
TI  - Healthy Living Partnerships to Prevent Diabetes (HELP PD): design and methods.
AB  - Although the Diabetes Prevention Program (DPP) developed a lifestyle weight loss
      intervention that has been demonstrated to prevent type 2 diabetes in high-risk
      individuals, it has yet to be widely adopted at the community level. The Healthy
      Living Partnership to Prevent Diabetes study (HELP PD) was designed to translate
      the DPP approach for use in community settings as a cost-effective intervention
      led by Community Health Workers (CHW's) and administered through a Diabetes Care
      Center (DCC). Approximately 300 overweight and obese (BMI 25-40 kg/m(2))
      individuals with prediabetes (fasting blood glucose 95-124 mg/dl) were randomly
      assigned to either a lifestyle weight loss intervention (LW) or an enhanced usual
      care comparison condition (UC). The goal of LW is >or=7% weight loss achieved
      through increases in physical activity (180 min/wk) and decreases in caloric
      intake (approximately 1500 kcal/day). The intervention consists of CHW-led group
      mediated cognitive behavioral meetings that occur weekly for 6 months and monthly
      thereafter for 18 months. UC consists of 2 individual meetings with a registered
      dietitian and a monthly newsletter. The primary outcome is change in fasting
      blood glucose. Secondary outcomes include cardiovascular risk factors, health
      related quality of life, and social cognitive variables. Outcomes are masked and
      are collected every 6 months. The cost-effectiveness of the program will also be
      assessed. A community-based program that is administered through local DCC's and
      that harnesses the experience of community members (CHW's) may be a promising
      strategy for the widespread dissemination of interventions effective at
      preventing type 2 diabetes in high risk individuals.

PMID- 19758581
TI  - Current knowledge about the functional roles of phosphorylative changes of
      membrane proteins in normal and diseased red cells.
AB  - With the advent of proteomic techniques the number of known post-translational
      modifications (PTMs) affecting red cell membrane proteins is rapidly growing but
      the understanding of their role under physiological and pathological conditions
      is incompletely established. The wide range of hereditary diseases affecting
      different red cell membrane functions and the membrane modifications induced by
      malaria parasite intracellular growth represent a unique opportunity to study
      PTMs in response to variable cellular stresses. In the present review, some of
      the major areas of interest in red cell membrane research have been considered as
      modifications of erythrocyte deformability and maintenance of the surface area,
      membrane transport alterations, and removal of diseased and senescent red cells.
      In all mentioned research areas the functional roles of PTMs are prevalently
      restricted to the phosphorylative changes of the more abundant membrane proteins.
      The insufficient information about the PTMs occurring in a large majority of the
      red membrane proteins and the general lack of mass spectrometry data evidence the
      need of new comprehensive, proteomic approaches to improve the understanding of
      the red cell membrane physiology.

PMID- 19758582
TI  - Mass and charge selective protein fractionation for the differential analysis of
      T-cell and CD34+ stem cell proteins from cord blood.
AB  - Studying biological processes through protein expression is difficult due to the
      dynamic flux of the proteome, the extreme diversity and heterogeneity, the wide
      range of cellular protein expression, and the limited detection range of
      technology. Fractionating complex biological mixtures can help overcome these
      issues but it can be a challenging process particularly when fractionating rare
      samples (<or=10(6)cells), due to the absolute limits in protein copy number and
      abundance. In this study, partitioning by charge and mass using the Microflow
      MF10 has been applied to CD34(+) haematopoietic stem/progenitor cells and
      CD4(+)/CD8(+) T-cells to separate proteins restricted by cell number. Less than
      10 microg total proteins per fraction was used for comparative analysis using SDS
      PAGE and identification of silver stained bands by LC-MS/MS revealed
      differentially expressed proteins between the 3 cell populations, which may be
      involved in cell differentiation.

PMID- 19758583
TI  - Cation-induced polyelectrolyte-polyelectrolyte attraction in solutions of DNA and
      nucleosome core particles.
AB  - The paper reviews our current studies on the experimentally induced cation
      compaction and aggregation in solutions of DNA and nucleosome core particles and
      the theoretical modelling of these processes using coarse-grained continuum
      models with explicit mobile ions and with all-atom molecular dynamics (MD)
      simulations. Recent experimental results on DNA condensation by cationic
      oligopeptides and the effects of added salt are presented. The results of MD
      simulations modelling DNA-DNA attraction due to the presence of multivalent ions
      including the polyamine spermidine and fragments of histone tails, which exhibit
      bridging between adjacent DNA molecules, are discussed. Experimental data on NCP
      aggregation, using recombinantly prepared systems are summarized. Literature data
      and our results of studying of the NCP solutions are compared with predictions of
      coarse-grained MD simulations, including the important ion correlation as well as
      bridging mechanisms. The importance of the results to chromatin folding and
      aggregation is discussed.

PMID- 19758584
TI  - Comparison of different force fields for the study of disaccharides.
AB  - Eighteen empirical force fields and the semi-empirical quantum method PM3CARB-1
      were compared for studying beta-cellobiose, alpha-maltose, and alpha-galabiose
      [alpha-D-Galp-(1-->4)-alpha-D-Galp]. For each disaccharide, the energies of 54
      conformers with differing hydroxymethyl, hydroxyl, and glycosidic linkage
      orientations were minimized by the different methods, some at two dielectric
      constants. By comparing these results and the available crystal structure data
      and/or higher level density functional theory results, it was concluded that the
      newer parameterizations for force fields (GROMOS, GLYCAM06, OPLS-2005 and CSFF)
      give results that are reasonably similar to each other, whereas the older
      parameterizations for Amber, CHARMM or OPLS were more divergent. However, MM3, an
      older force field, gave energy and geometry values comparable to those of the
      newer parameterizations, but with less sensitivity to dielectric constant values.
      These systems worked better than MM2 variants, which were still acceptable.
      PM3CARB-1 also gave adequate results in terms of linkage and exocyclic torsion
      angles. GROMOS, GLYCAM06, and MM3 appear to be the best choices, closely followed
      by MM4, CSFF, and OPLS-2005. With GLYCAM06 and to a lesser extent, CSFF, and OPLS
      2005, a number of the conformers that were stable with MM3 changed to other
      forms.

PMID- 19758585
TI  - One-pot synthesis of highly functionalized morphans from C-glycosides.
AB  - Highly functionalized morphan derivatives were synthesized from nitroalkene 2'
      (oxoalkyl)-C-glycosides by a tandem reaction that created three (two C-N and one
      C-C) new bonds and four stereogenic centers in a one-pot procedure under very
      mild conditions without the use of expensive reagents. The transformation was
      achieved from a beta-elimination/Michael addition cascade, followed by Michael
      addition of the amine and intramolecular enamination. In the presence of sodium
      cyanoborohydride the iminium intermediate was reduced in situ to afford the
      desired morphans.

PMID- 19758586
TI  - [Interest in morbidity scores and classification in general surgery].

PMID- 19758587
TI  - Cellular uptake, subcellular distribution and toxicity of arsenic compounds in
      methylating and non-methylating cells.
AB  - Arsenic is a known human carcinogen, inducing tumors of the skin, urinary
      bladder, liver and lung. Inorganic arsenic, existing in highly toxic trivalent
      and significantly less toxic pentavalent forms, is methylated to mono- and di
      methylated species mainly in the liver. Due to the low toxicity of pentavalent
      methylated species, methylation has been regarded as a detoxification process for
      many years; however, recent findings of a high toxicity of trivalent methylated
      species have indicated the contrary. In order to elucidate the role of speciation
      and methylation for the toxicity and carcinogenicity of arsenic, systematic
      studies were conducted comparing cellular uptake, subcellular distribution as
      well as toxic and genotoxic effects of organic and inorganic pentavalent and
      trivalent arsenic species in both non-methylating (urothelial cells and
      fibroblasts) and methylating cells (hepatocytes). The membrane permeability was
      found to be dependent upon both the arsenic species and the cell type. Uptake
      rates of trivalent methylated species were highest and exceeded those of their
      pentavalent counterparts by several orders of magnitude. Non-methylating cells
      (urothelial cells and fibroblasts) seem to accumulate higher amounts of arsenic
      within the cell than the methylating hepatocytes. Cellular uptake and extrusion
      seem to be faster in hepatocytes than in urothelial cells. The correlation of
      uptake with toxicity indicates a significant role of membrane permeability
      towards toxicity. Furthermore, cytotoxic effects are more distinct in
      hepatocytes. Differential centrifugation studies revealed that elevated
      concentrations of arsenic are present in the ribosomal fraction of urothelial
      cells and in nucleic and mitochondrial fractions of hepatic cells. Further
      studies are needed to define the implications of the observed enrichment of
      arsenic in specific cellular organelles for its carcinogenic activity. This
      review summarizes our recent research on cellular uptake, distribution and
      toxicity of arsenic compounds in methylating and non-methylating cells.

PMID- 19758588
TI  - Bioaccumulation of metals and effects of a landfill in small mammals Part III:
      Structural alterations.
AB  - The leachates from the Garraf landfill located in a protected site (NE Spain)
      contain several potentially toxic substances such as heavy metals. Here we report
      the histopathological alterations produced by this pollution in wild specimens of
      an omnivorous species, the wood mouse, Apodemus sylvaticus, and an insectivorous
      species, the greater white-toothed shrew, Crocidura russula. Hepatic tissue
      presented the most severe alterations in both the species, namely cell cycle
      arrest (apoptosis and necrosis), inflammation, preneoplasic nodules, vacuolation
      and microsteatosis. The kidneys were altered more in the mice (presenting tubular
      necrosis and dilatation, inflammation, and cylinders) than in the shrews,
      suggesting that different metabolic pathways render shrews more tolerant to renal
      toxicity induced by pollutants. No pollution-related alterations were observed in
      lung, spleen, pancreas, gonads, oesophagus, intestine, or adrenals. We conclude
      that the two species could be used in conjunction as bioindicators to assess the
      effects of environmental pollution at different trophic levels.

PMID- 19758589
TI  - EMMPRIN and its ligand cyclophilin A regulate MT1-MMP, MMP-9 and M-CSF during
      foam cell formation.
AB  - Upon coincubation with platelets, CD34(+) progenitor cells have the potential to
      differentiate into foam cells, and thereby may promote the progression of
      atherosclerosis. The exact mechanism of MMP-regulation during the cellular
      differentiation process to foam cells is still unclear. Thus, we investigated the
      role of EMMPRIN (CD147) and its ligand cyclophilin A (CyPA) during foam cell
      formation originating from both monocytes/macrophages and CD34(+) progenitor
      cells. METHODS AND RESULTS: Differentiation of CD34(+) progenitor to foam cells
      was analyzed in a coculture model of progenitor cells and platelets. While
      CD34(+) cells did not express EMMPRIN or MT1-MMP, mature foam cells strongly
      expressed EMMPRIN, which was associated with MT1-MMP expression as well as MMP-9.
      Gene silencing of EMMPRIN by siRNA during the cell differentiation process
      hindered not only the upregulation of MMPs (MT1-MMP, MMP-9), but also the
      secretion of the cytokine M-CSF. During the differentiation process CyPA was
      substantially released into the supernatant. The presence of the CyPA inhibitor
      NIM811 significantly reduced MMP-9 secretion during the differentiation process.
      Similar results were obtained using the classical pathway of foam cell formation
      by coincubating human macrophages with AcLDL. Additionally, the presence of
      soluble EMMPRIN ligands (CyPA, recombinant EMMPRIN) further enhanced MMP-9
      secretion by mature foam cells. Consistently, CyPA and EMMPRIN were found in
      atherosclerotic plaques of ApoE-deficient mice by immunohistochemistry.
      CONCLUSION: EMMPRIN is upregulated during the differentiation process from
      CD34(+) progenitor cells to foam cells, whereas its ligand, CyPA, is released.
      The CyPA/EMMPRIN activation pathway may play a relevant role in promoting the
      vulnerability of atherosclerotic plaques.

PMID- 19758590
TI  - Is uric acid protective or deleterious in acute ischemic stroke? A prospective
      cohort study.
AB  - Contrasting observations have been made between serum urate and ischemic stroke
      outcomes in studies involving Caucasian populations. To assess the hypothesis
      that urate is associated with stroke outcomes, a prospective follow-up study was
      performed in a cohort of Asian patients with ischemic stroke. Patients diagnosed
      with transient ischemic attack, first or recurrent ischemic stroke were included
      in this study. Serum urate, measured using high-performance liquid
      chromatography, was correlated with 12-month functional and vascular stroke
      outcomes. Poor functional outcome was defined as a modified Rankin scale
      exceeding 2 and vascular outcome was defined as a composite of recurrent stroke,
      myocardial infarction or vascular death during the study period. A total of 503
      patients of mean age 63 (SD 12) years were included. A U-shaped relationship
      between urate quartiles and poor functional outcomes was demonstrated. More
      patients with low (<280microM) and high (>410microM) urate levels had poor
      functional outcomes (36% and 27% respectively), compared to those with urate
      levels between 340 and 410microM (14%). No significant relationship was observed
      between urate and vascular outcomes. Depending on its level, serum urate may
      exhibit protective and deleterious effects on stroke outcomes.

PMID- 19758591
TI  - Blood vessel buckling within soft surrounding tissue generates tortuosity.
AB  - The stability of blood vessel under lumen pressure load is essential to the
      maintenance of normal arterial function. Previous mechanical models showed that
      blood vessels may buckle into a half sine wave but arteries and veins in vivo
      often demonstrate tortuous paths with multiple waves. The objective of this study
      was to analyze the buckling of blood vessels under lumen pressure with
      surrounding tissue support. Blood vessels were modeled as elastic cylindrical
      vessels within an elastic substrate. Buckling equations were established to
      determine the critical pressure and the wavelength. These equations and
      simulation results demonstrated that blood vessels do take higher order mode
      shapes when buckling inside an elastic substrate while they take the basal mode
      shape without the substrate. The wave number increases i.e. blood vessels take a
      higher mode shape, as the stiffness of the substrate increases. These results
      suggest that mechanical buckling is a possible mechanism for the development of
      tortuous blood vessels. The current model provides a powerful tool for further
      studying the tortuosity of arteries and veins.

PMID- 19758592
TI  - Mixing and matching in ceramic-on-metal hip arthroplasty: an in-vitro hip
      simulator study.
AB  - The clinical success of second-generation metal-on-metal hip replacement and the
      good tribological performance of alumina ceramic revived an interest in hip
      articulation as a solution to reduce wear. This study was aimed at characterizing
      the wear behaviour of new hybrid ceramic-on-metal bearings. In particular, this
      study investigated the wear behaviour of ceramic-on-metal hip components (three
      different diameters configurations: 28, 32 and 36 mm), not specifically proposed
      to be coupled, in order to compare them with ceramic-on-ceramic, which is
      considered to be the gold standard for wear resistance. For this purpose, the
      weight loss over a standard wear simulation was monitored. Moreover, scanning
      electronic microscope observations were used to verify if any carbides removal,
      for the metallic components, triggered wears debris production promoting abrasive
      third-body wear. After five million cycles, our results showed significantly
      greater wear-in ceramic-on-metal compared with ceramic-on-ceramic, and
      significant greater wear for the 32-mm diameter compared with the 36-mm one. Our
      findings showed an increase in wear for the proposed hybrid specimens with
      respect to that of the ceramic-on-ceramic ones confirming that even in the case
      of ceramic-on-metal bearings, mixing and matching could not prove effective wear
      behaviour, not even comparable with that of the ceramic-on-ceramic gold standard.
      Wear patterns and roundness tolerances certainly discourage the coupling of
      components not specifically intended to be coupled. Unsuitable geometrical
      conformity could, in fact, result in a poor dynamic behaviour and lead to
      clinical failure.

PMID- 19758593
TI  - Columns switch recycling size exclusion chromatography for high resolution
      protein separation.
AB  - Columns switch recycling size exclusion chromatography (csrSEC) was proposed to
      achieve high resolution protein separation with good biocompatibility. Proteins
      were firstly separated by two serially coupled SEC columns, and fractions were in
      sequence switched back to the first column by two-position valves for further
      separation in terms of close-loop recycling until satisfactory resolution was
      achieved. Compared to SEC, the separation window was broadened by increasing
      column length via cycling without further increase on back pressure. Compared to
      recycling SEC (rSEC), the overtaking of later eluted components by early eluted
      ones after several cycles could be avoided for complex sample analysis, by
      parking fractions in the second SEC column before transferred in turn back to the
      first one for cycling ordinally. In our experiments, the baseline separation of
      five proteins with molecular weight ranging from 10 kDa to 80kDa was achieved by
      csrSEC. Furthermore, a multidimensional csrSEC-RPLC platform was constructed, and
      peak capacity up to 3600 was obtained for protein separation. All these results
      demonstrated that csrSEC is a promising protein separation mode with good
      biocompatibility, broadened separation window and improved resolution.

PMID- 19758594
TI  - Support-free pulsed liquid-liquid chromatography.
AB  - A simple technique of support-free liquid-liquid chromatography is suggested that
      operates without incorporation of a centrifuge. The pulsed chromatography
      apparatus consists of a stationary coiled tube and a pulsation device to produce
      reciprocating motion of liquid phases within each individual coil segment. This
      reciprocating motion generates a centrifugal force field varying in intensity and
      direction that leads to an improved mixing of the two liquid phases and retains
      the stationary phase in the coiled tubing. The intensity of the back and forth
      motion of liquid phases within each coil unit can be varied by varying the
      frequency and/or the amplitude of the pulsations generated by the pulsation
      device. As the magnitude of the stationary phase retention is of paramount
      importance for success of the technique, the retention of the stationary phase in
      the pulsed coil column was experimentally studied. A few experiments were
      conducted to test the chromatographic behavior of valeric (n-pentanoic) and
      caproic (n-hexanoic) acids. The results obtained demonstrate the potential of the
      new separation method for preparative purposes.

PMID- 19758595
TI  - Capabilities of mixed-mode liquid chromatography coupled to inductively coupled
      plasma mass spectrometry for the simultaneous speciation analysis of inorganic
      and organically-bound selenium.
AB  - This work investigates for the first time the potential of mixed-mode (anion
      exchange with reversed-phase) high performance liquid chromatography coupled to
      inductively coupled plasma mass spectrometry (ICP-MS) for the simultaneous
      retention and selective separation of a range of inorganic and organically-bound
      selenium (Se) species. Baseline separation and detection of selenocystine
      (SeCys(2)), Se-methyl-selenocysteine (SeMC), selenomethionine (SeMet),
      methylseleninic acid (MSA), selenite, gamma-glutamyl-methyl-selenocysteine (gamma
      glutamyl-SeMC), and selenate in a Se standard mixture by mixed-mode HPLC-ICP-MS
      was achieved by switching between two citrate mobile phases of different pH and
      ionic strength within a single chromatographic run of 20 min. Limits of detection
      obtained for these Se species ranged from 80 ng kg(-1) (for SeMC) to 123 ng kg(
      1) (for selenate). Using this approach as developed for selenium speciation, an
      adequate separation of inorganic and organic As compounds was also achieved.
      These include arsenite, arsenate, arsenobetaine (AsB) and dimethylarsenic acid
      (DMA), which may coexist with Se species in biological samples. Application of
      the newly proposed methodology to the investigation of the elemental species
      distribution in watercress (used as the model sample) after enzymatic hydrolysis
      or leaching in water by accelerated solvent extraction (ASE) was addressed. Only
      SeMet, SeMC and selenate could be tentatively identified in watercress extracts
      by mixed-mode HPLC-ICP-MS and retention time matching with standards. Recoveries
      (n=3) of these Se species from samples spiked with standards averaged 102% (for
      SeMC), 94.9% (for SeMet) and 98.3% (for selenate). Verification of the presence
      of SeMet and SeMC in an enzymatic watercress extract was achieved by on-line HPLC
      ESI MS/MS in selected reaction monitoring (SRM) mode.

PMID- 19758596
TI  - Aggregation behavior in water of new imidazolium and pyrrolidinium
      alkycarboxylates protic ionic liquids.
AB  - A novel class of anionic surfactants was prepared through the neutralization of
      pyrrolidine or imidazole by alkylcarboxylic acids. The compounds, namely the
      pyrrolidinium alkylcarboxylates ([Pyrr][C(n)H(2n+1)COO]) and imidazolium
      alkylcarboxylates ([Im][C(n)H(2n+1)COO]), were obtained as ionic liquids at room
      temperature. Their aggregation behavior has been examined as a function of the
      alkyl chain length (from n=5 to 8) by surface tensiometry and conductivity.
      Decreases in the critical micelle concentration (cmc) were obtained, for both
      studied PIL families, when increasing the anionic alkyl chain length (n).
      Surprisingly, a large effect of the alkyl chain length was observed on the
      minimum surface area per surfactant molecule (A(min)) and, hence the maximum
      surface excess concentration (Gamma(max)) when the counterion was the
      pyrrolidinium cation. This unusual comportment has been interpreted in term of a
      balance between van der Waals and coulombic interactions. Conductimetric
      measurements permit determination of the degree of ionization of the micelle (a)
      and the molar conductivity (Lambda(M)) of these surfactants as a function of n.
      The molar conductivities at infinite dilution in water (Lambda(infinity)) of the
      [Pyrr]+ and [Im]+ cations have been then determined by using the classical
      Kohlraush equation. Observed change in the physicochemical, surface, and micellar
      properties of these new protonic ionic liquid surfactants can be linked to the
      nature of the cation. By comparison with classical anionic surfactants having
      inorganic counterions, pyrrolidinium alkylcarboxylates and imidazolium
      alkylcarboxylates exhibit a higher ability to aggregate in aqueous solution,
      demonstrating their potential applicability as surfactant.

PMID- 19758597
TI  - Antibacterial activity of DLC films containing TiO2 nanoparticles.
AB  - Diamond-like carbon (DLC) films have been the focus of extensive research in
      recent years due to their potential applications as surface coatings on
      biomedical devices. Titanium dioxide (TiO2) in the anatase crystalline form is a
      strong bactericidal agent when exposed to near-UV light. In this work we
      investigate the bactericidal activity of DLC films containing TiO2 nanoparticles.
      The films were grown on 316L stainless-steel substrates from a dispersion of TiO2
      in hexane using plasma-enhanced chemical vapor deposition. The composition,
      bonding structure, surface energy, stress, and surface roughness of these films
      were also evaluated. The antibacterial tests were performed against Escherichia
      coli (E. coli) and the results were compared to the bacterial adhesion force to
      the studied surfaces. The presence of TiO2 in DLC bulk was confirmed by Raman
      spectroscopy. As TiO2 content increased, I(D)/I(G) ratio, hydrogen content, and
      roughness also increased; the films became more hydrophilic, with higher surface
      free energy and the interfacial energy of bacteria adhesion decreased.
      Experimental results show that TiO2 increased DLC bactericidal activity. Pure DLC
      films were thermodynamically unfavorable to bacterial adhesion. However, the
      chemical interaction between the E. coli and the studied films increased for the
      films with higher TiO2 concentration. As TiO2 bactericidal activity starts its
      action by oxidative damage to the bacteria wall, a decrease in the interfacial
      energy of bacteria adhesion causes an increase in the chemical interaction
      between E. coli and the films, which is an additional factor for the increasing
      bactericidal activity. From these results, DLC with TiO2 nanoparticles can be
      useful for producing coatings with antibacterial properties.

PMID- 19758598
TI  - Epithelial and pancreatic choristoma in bovine lymph nodes.
AB  - Lymph nodes from 186 cows were evaluated as part of a bovine tuberculosis
      eradication programme. The mediastinal lymph nodes of 13 animals contained
      atypical structures. In 12 cases (6.45%) these consisted of multiple epithelial
      structures and, in one case, of pancreatic-like tissue. Immunohistochemistry
      (IHC) revealed that the epithelial structures were consistent with respiratory
      epithelium and with ectopic pancreatic tissue, respectively. To the best of our
      knowledge these are the first histological and immunohistochemical descriptions
      of epithelial and pancreatic choristomas in bovine lymph nodes.

PMID- 19758599
TI  - Predictors of treatment response to fluvoxamine in obsessive-compulsive disorder:
      an fMRI study.
AB  - Recent neuroimaging studies suggest that the pathophysiology of obsessive
      compulsive disorder (OCD) may involve more widely distributed large-scale brain
      systems, including the parietal, occipital, and cerebellar areas, rather than the
      conventional orbitofronto-striatal model. We hypothesized that not only
      orbitofrontal cortex and caudate nucleus activities but also posterior brain
      regions might be associated with subsequent treatment response to serotonin
      reuptake inhibitors in OCD. The participants were 17 patients with OCD. Each
      patient was required to undergo fluvoxamine pharmacotherapy for 12 weeks. Before
      treatment, fMRI images of the subjects were obtained in the context of a symptom
      provocation paradigm. The percentage changes in total Yale-Brown Obsessive
      Compulsive Scale (Y-BOCS) scores, from pre- to post-treatment, served as the
      index of treatment response. Statistical Parametric Mapping was used to identify
      brain loci where pre-treatment brain activation significantly correlated with the
      subsequent treatment response. Fifteen of 17 patients completed the 12-week
      treatment. During the symptom provocation task, patients showed brain activation
      in the left superior temporal gyrus (STG), left precuneus, left frontal cortices,
      right cerebellum, and right frontal cortices. We found that pre-treatment
      activation in the right cerebellum (Z-score=5.10, x,y,z=22,-84,-18) and the left
      STG (Z-score=4.95, x,y,z=-62,-22,0) was positively correlated with the
      improvement in the Y-BOCS score. Our results suggest that pre-treatment
      activation in the right cerebellum and in the left STG predict subsequent
      reduction in OCD symptom severity. There is every possibility that fMRI can be
      used as a tool to predict treatment response.

PMID- 19758600
TI  - Functional impact of biological rhythm disturbance in bipolar disorder.
AB  - Bipolar disorder (BD) is characterized by frequent recurrence, incomplete
      recovery, cognitive dysfunction and poor functioning. Impairment lingers in the
      interepisodic period and mechanisms leading to this dysfunctional state are not
      fully comprehended. To our knowledge the association of biological rhythm
      dysfunction with functioning in BD has not been assessed directly. The objective
      of this study was to measure and quantify the impact of rhythm dysfunction on
      interepisodic functioning in BD. We also tested the association between executive
      functioning and sleep and rhythm problems. Eighty-one outpatients with BD and 79
      matched control subjects were consecutively recruited. Functional impairment was
      assessed with the Functioning Assessment Short Test (FAST) and biological rhythms
      with the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN). A
      subsample had their executive functioning assessed with the Wisconsin Card
      Sorting Test (WCST). Patients and control subjects were well matched. Functioning
      and rhythm scores were correlated in patients and control subjects. The BRIAN
      score was the strongest predictor of functioning in the regression model.
      Biological rhythms partially mediated the impairment associated with bipolar
      disorder. The rhythm score was also associated with executive functioning.
      Biological rhythm dysfunction was a potent predictor of functioning in
      interepisodic patients with bipolar disorder; it may also mediate much of the
      disorder-induced disability. These results further the notion that biological
      rhythms may be interesting targets for diverse interventions aiming to improve
      functioning and prevent relapse in interepisodic bipolar disorder.

PMID- 19758601
TI  - Brainstem pathology and non-motor symptoms in PD.
AB  - Parkinson's disease (PD) is considered a multisystem disorder involving
      dopaminergic, noradrenergic, serotoninergic, and cholinergic systems,
      characterized by motor and non-motor symptoms. The causes of the non-motor
      symptoms in PD are multifactorial and unlikely to be explained by single lesions.
      However, several evidence link them to damage of specific brainstem nuclei.
      Numerous brainstem nuclei are engaged in fundamental homeostatic mechanisms,
      including gastrointestinal regulation, pain perception, mood control, and sleep
      wake cycles. In addition, these nuclei are locally interconnected in a complex
      manner and are subject to supraspinal control. The objective of this review is to
      provide a better overview of the current knowledge about the consequences of the
      involvement of specific brainstem nuclei to the most prevalent non-motor symptoms
      occurring in PD. The multidisciplinary efforts of research directed to these non
      nigral brainstem nuclei, in addition to the topographical and chronological
      spread of the disease - especially in the prodromal stages of PD, are discussed.

PMID- 19758602
TI  - The pathophysiological basis of sensory disturbances in Parkinson's disease.
AB  - The diagnosis of Parkinson's disease (PD) is still based on the recognition of
      the cardinal motor features. However, it is now recognized that non-motor
      manifestations (NMM) may actually precede the emergence of motor manifestations.
      NMM are very frequently present in the overall population of PD patients and are
      a major determinant of their quality of life. In this article we discuss the
      origin of sensory manifestations in PD, particularly focus on pain mechanisms,
      which is the most frequent and better studied NMM. Analysis of experimental and
      clinical data reveals that the basal ganglia (BG) indeed have an anatomo
      functional organization which sustains sensory functions. In addition, the
      dopaminergic system is also engaged in the modulation and integration of sensory
      information and the response to pain. In patients with PD, pain is often related
      with motor fluctuations and dyskinesias induced by dopaminergic treatments, which
      suggest some common mechanisms with the origin of motor complications in PD.
      Clinically, sensory manifestations are often disturbing and poorly treated and
      may occasionally become a major cause of disability for PD patients. Thus, more
      clinical and basic studies are warranted to clarify pain mechanisms in PD, with
      the aim of achieving better treatments.

PMID- 19758603
TI  - Clinical applicability of a mathematical model in assessing the functional
      ability of the communicating arteries of the circle of Willis.
AB  - BACKGROUND: The brain collateral blood supply, which is essential in patients
      suffering from significant stenoses or occlusions of the extracranial arteries,
      remains difficult to assess accurately in practice. We compared data obtained
      from transcranial color-coded duplex sonography (TCCD) combined with carotid
      compression tests to morphometric autopsy data and to results given by a
      mathematical model of the cerebral macrocirculation. METHODS AND RESULTS: In 16
      moribund patients, anterior and posterior communicating arteries of the circle of
      Willis were divided into functional and non-functional based on the results of
      the TCCD combined with carotid compression tests. After death of the patients
      diameters and lengths of the main intracranial arteries were measured at autopsy
      and these values were treated with a mathematical model for calculating blood
      flow and blood pressure in all the segments of the arterial network. The
      diameters and the blood flows through the communicating arteries were found to be
      significantly higher in the group of functional arteries than in that of non
      functional ones. However, blood flow was also shown to be dependent on other
      parameters such as the pressure difference between the two ends of the vessel.
      CONCLUSION: Our data indicate that functional ability of the Willisian
      collaterals depends on morphological and functional parameters, and is therefore
      better assessed by a functional method, such as TCCD, than by a solely
      morphological one, such as cerebral angiography. Mathematically based circulation
      modeling, when it will be possible, could be a more comprehensive tool for
      delineating patients at a higher risk for hemodynamic cerebrovascular
      insufficiency.

PMID- 19758604
TI  - Radiological features of craniopharyngiomas located in the posterior fossa.
AB  - BACKGROUND AND PURPOSE: Posterior fossa craniopharyngiomas (PFCP) constitute 1.6
      4% of all craniopharyngiomas and have long been neglected. The purpose of our
      study was to investigate neuroimaging features of this unique modality in a
      cohort of 7 cases. METHODS: CT and/or MR imaging features (with and without
      contrast enhancement) of 7 patients who underwent craniotomies for histologically
      proved PFCP were reviewed and analyzed retrospectively. Surgical management was
      also reviewed. RESULTS: All PFCPs arised from sellar/suprasellar region and
      extended into unilateral cerebellopontine angle in 6 cases, and bilateral in 1
      case. Seven tumors were of retrochiasmatic origin and 5 of 7 were of retrostalk
      growth pattern with location in the ventral area of brain stem. On CT scans,
      tumors were isodense in solid component and hypodense in cystic component with
      (4/7) or without calcification (3 /7) and destruction in sellae turcia (2/7).
      Tumors demonstrated cyst formation (7/7) with hypointense on T1-weighted imaging
      and hyperintense on T2-weighted imaging in 5 cases, hyperintense both on T1- and
      T2-weighted imaging in 2 cases. The solid components and capsule revealed mild to
      moderate inhomogeneous enhancement after administration of contrast agents. Total
      tumor removal was accomplished in 5 cases, subtotal removal and partial removal
      in 1 case respectively. CONCLUSIONS: PFCPs are well demarcated, contrast-enhanced
      tumors, typically with cystic parts or purely cyst. Most of PFCPs demonstrate a
      retrostalk growth pattern and characteristic connection. Tumor with cystic
      component arises from sellar region and then extends to posterior fossa, which
      should be strongly suspected as a PFCP. The combined supra- and infratentorial
      approach is an ideal choice for surgical management of PFCP.

PMID- 19758605
TI  - Is RNA manipulation a viable therapy for spinal muscular atrophy?
AB  - Childhood spinal muscular atrophy (SMA) is an autosomal recessive disorder
      characterised by loss of the alpha motor neurones of the spinal cord. SMA is
      cause by mutations in the survival motor neuron (SMN) gene. There are two copies
      of the SMN gene: SMN1 and SMN2. The two genes differ by only 11 nucleotides at
      the genomic level. One of these is a C to T single nucleotide polymorphism (SNP)
      at position 6 in exon 7. This change alters an exon splicing enhancer in exon 7,
      meaning that while SMN1 expresses exclusively full-length protein containing exon
      7, SMN2 is predominantly alternatively spliced and expresses a truncated
      transcript lacking exon 7 (SMN7). As all SMA patients are effectively null for
      SMN1 but retain at least one copy of SMN2, patients express considerably lower
      levels of functional SMN protein compared with uneffected individuals. Therefore,
      SMA is triggered by a fall in the levels of expressed full-length protein, and
      the levels expressed by the retained SMN2 gene control the severity. As a result,
      RNA manipulation to suppress the alternative splicing event and thus increase SMN
      exon 7 inclusion has emerged as an attractive therapeutic approach. In this
      review we have discussed the current state of bifunctional RNAs as a viable
      therapy, concentrating on recent advances and overall implications of this
      research on SMA.

PMID- 19758606
TI  - Brain-derived neurotrophic factor and TrkB receptor in experimental autoimmune
      encephalomyelitis and multiple sclerosis.
AB  - The interaction between the immune and nervous systems can be both detrimental
      and beneficial. Experimental autoimmune encephalomyelitis (EAE) is an animal
      model of autoimmune demyelination that histologically and clinically mimics
      multiple sclerosis (MS). Myelin-reactive T cells produce and release brain
      derived neurotrophic factor (BDNF) directly in the central nervous system, which
      stimulates tissue repair after traumatic injury. In EAE and MS, T cells in the
      vicinity of actively demyelinating lesions express BDNF, suggesting a
      neuroinflammatory reaction that is designed to limit brain damage and contribute
      to the repair process. Despite some evidence supporting MS therapies that enhance
      BDNF production by immune cells, no published reports have actually demonstrated
      that increased BDNF production can substantially ameliorate the clinical symptoms
      of MS. BDNF binds to a small subset of peripheral T cells that express TrkB,
      which is the BDNF receptor. This binding confers a partial resistance to
      apoptosis upon T cell activation, which could underlie the chronic nature of the
      inflammatory process. Here we will review the main aspects of BDNF and TrkB
      receptor involvement in neuroprotective autoimmunity in both EAE and MS. We will
      also discuss the latest findings with respect to the role of the BDNF/TrkB axis
      in regulating the survival of autoreactive T cells, with a focus on potential
      selectively immunomodulating strategies that may favor neuroprotection in MS.

PMID- 19758607
TI  - The Prevention of Post-Partum Relapses with Progestin and Estradiol in Multiple
      Sclerosis (POPART'MUS) trial: rationale, objectives and state of advancement.
AB  - Multiple sclerosis (MS) affects 1 in 1000 people in western countries, mainly
      women in their childbearing years. It is an autoimmune disease of the central
      nervous system, which results in a chronic focal inflammatory response with
      subsequent demyelination and axonal loss. It usually begins with acute episodes
      of neurological dysfunction, the relapses, followed by periods of partial or
      complete remission. This relapsing-remitting phase is usually followed by a
      steady, continuous and irreversible worsening of the neurological dysfunction,
      which characterizes the progressive phase of the disease. Recent prospective
      studies reported a significant decline by two-third in the rate of relapses
      during the third trimester of pregnancy and a significant increase by two-third
      during the first three months post-partum by comparison to the relapse rate
      observed during the year prior to the pregnancy. These dramatic changes in the
      relapse rate occur at a time when impregnation of many substances, among which
      sexual steroids, is at its highest, before a dramatic decline to the pre
      pregnancy levels, immediately following delivery. It may be hypothesized that
      sexual steroids could exert beneficial effects through a modulation of the immune
      state with a lowering of the pro-inflammatory lymphocyte responses of the Th1
      type and an enhancement of anti-inflammatory responses of the Th2 type. They may
      also play a direct role in remyelination of central nervous system lesions, as
      they do in the peripheral nervous system, where progesterone increases the extent
      of myelin sheath formation after a cryolesion of the male mouse sciatic nerve.
      The POPART'MUS study is a European, multicentre, randomized, placebo-controlled
      and double-blind clinical trial, which aims to prevent MS relapses related to the
      post-partum condition, by administrating high doses of progestin, in combination
      with endometrial protective doses of estradiol. Treatment is given immediately
      after delivery and continuously during the first three months post-partum. At
      present, 126 patients have been enrolled and 107 patients have completed the
      protocol. Assuming the results of the trial to be positive, this new treatment
      could be considered in the relapsing-remitting phase of the disease in women afar
      from pregnancy and post-partum. The trial is registered under the reference
      NTC00127075.

PMID- 19758609
TI  - Selective antegrade cerebral perfusion via right axillary artery cannulation
      reduces morbidity and mortality after proximal aortic surgery.
AB  - INTRODUCTION: Selective antegrade cerebral perfusion is a well-described
      neuroprotective technique used in proximal aortic surgery. This study
      investigated whether selective antegrade cerebral perfusion is associated with
      improved outcomes in both emergency and elective settings compared with deep
      hypothermic circulatory arrest alone. METHODS: Retrospective review was performed
      for all cases of proximal aortic surgery between January 2004 and May 2007. Of
      these 271 patients, 105 had emergency and 166 had elective operation. Selection
      bias was controlled using propensity scoring methods. Multivariable logistic
      regression analysis was used to model adverse outcomes as a function of selective
      antegrade cerebral perfusion, emergency status, and their interaction, adjusted
      for the propensity score. Adjusted odds ratios were formulated with 95%
      confidence intervals. RESULTS: Operative mortality occurred in 12.1% (33/271) of
      patients: 8.8% (18/205) in patients with selective antegrade cerebral perfusion
      versus 22.7% (15/66) in those with deep hypothermic circulatory arrest alone (P =
      .003). Temporary neurologic dysfunction occurred in 5.9% (15/255) of patients:
      4.5% (9/198) in selective antegrade cerebral perfusion versus 10.5% (6/57) in
      deep hypothermic circulatory arrest alone (P = .09). Stroke occurred in 4.3%
      (11/255) of patients with no difference between groups. In the elective setting,
      selective antegrade cerebral perfusion was associated with a significant decrease
      in operative mortality compared with deep hypothermic circulatory arrest alone.
      Overall, selective antegrade cerebral perfusion was associated with shorter
      intensive care unit and ventilator times and fewer renal and pulmonary
      complications. Significant multivariable predictors of operative mortality were
      emergency status, previous coronary surgery, and cardiopulmonary bypass time.
      CONCLUSIONS: Use of selective antegrade cerebral perfusion confers a survival
      advantage during proximal aortic surgery that is most apparent in the elective
      setting. Improved resource utilization and fewer pulmonary and renal
      complications were observed in patients with selective antegrade cerebral
      perfusion.

PMID- 19758610
TI  - Differing perceptions of quality of life in patients with prostate cancer and
      their doctors.
AB  - PURPOSE: As the number of prostate cancer survivors increases, urologists must
      recognize their quality of life impairment. In the past physician ratings of
      patient symptoms did not correlate with patient self-assessments. We determined
      if urologists have improved their reporting of patient health related quality of
      life. We also investigated if urologists assessed health related quality of life
      more accurately in the short or long term. MATERIALS AND METHODS: We identified
      1,366 men from CaPSURE, a national, prospective cohort, who had undergone
      prostatectomy, brachytherapy or external beam radiation therapy. At each visit
      urologists assessed fatigue, pain, and sexual, urinary and bowel dysfunction.
      Participants independently completed the SF-36 and the UCLA-PCI. We contrasted
      the frequency of impairment reported by physicians and participants in select
      health related quality of life domains in the short (less than 1 year) and long
      (greater than 2 years) term. We also compared physician-patient concordance
      between the periods 1995 to 2000 and 2001 to 2007. RESULTS: In short-term and
      long-term followup, and for the 1995 to 2000 and 2001 to 2007 cohorts, physician
      and participant assessments differed in all analyzed domains. Urologists noted
      impairment in urinary and sexual function more often than fatigue or pain.
      Disagreement between physician and participant ratings did not vary dramatically
      from short-term to long-term followup, or from the earlier to the later cohort.
      CONCLUSIONS: In men treated for localized prostate cancer physician ratings of
      symptoms do not correlate well with patient self-assessments of health related
      quality of life. Physician reporting did not improve over time. It is
      increasingly important to recognize and address impairments in quality of life
      from prostate cancer and its treatment.

PMID- 19758611
TI  - Increased low density lipoprotein and increased likelihood of positive prostate
      biopsy in black americans.
AB  - PURPOSE: Differences in prostate cancer incidence, grade and stage at diagnosis,
      and survival in black vs nonblack men are well documented. Recent studies
      indicate that lipids may have a role in oncogenesis, including that of prostate
      cancer. We investigated the relationship between circulating lipids in black and
      nonblack patients, and newly diagnosed prostate cancer. MATERIALS AND METHODS:
      The study population included consecutive patients who underwent prostate biopsy
      for increased prostate specific antigen and/or abnormal digital rectal
      examination at Atlanta Veterans Affairs Medical Center. Age, race, prostate
      specific antigen, prostate volume, body mass index, family history, high and low
      density lipoprotein, triglyceride and cholesterol lowering medications were
      included in data analysis. RESULTS: A total of 1,775 men with complete
      information were included in data analysis. A total of 521 black and 451 white
      men had positive biopsies. Using 100 mg/dl or less as the referent the adjusted
      OR reflecting the association of low density lipoprotein and prostate cancer
      diagnosis in black men was 1.49 (95% CI 1.04-2.13, p = 0.031), 1.51 (95% CI 0.96
      2.39, p = 0.076) and 3.24 (95% CI 1.59-6.92, p = 0.002) for low density
      lipoprotein greater than 100 to 130, greater than 130 to 160 and greater than 160
      mg/dl, respectively. Corresponding results in nonblack men showed no significant
      association. CONCLUSIONS: Increased serum low density lipoprotein is associated
      with an increased likelihood of prostate cancer diagnosis in black men but not in
      nonblack men. This association is strongest in the highest low density
      lipoprotein risk category. The reasons for the racial differences are unknown but
      may include genetic, dietary or other environmental factors.

PMID- 19758612
TI  - Editorial comment.

PMID- 19758613
TI  - Urinary diversion trends at a high volume, single American tertiary care center.
AB  - PURPOSE: We analyzed patient characteristics and practice patterns at our
      institution with time, and identified current patterns and factors contributing
      to the choice of urinary diversion. MATERIALS AND METHODS: We reviewed the
      records of 553 consecutive radical cystectomy and urinary diversions performed
      from January 2000 to July 2005. Multivariate analysis was done to determine
      significant differences in diversion choice. RESULTS: We analyzed the records of
      539 patients, including 338 with an ileal conduit and 201 with a neobladder.
      Patients with a neobladder were younger (mean age 62 vs 71 years) and had fewer
      comorbidities (American Society of Anesthesiologists class greater than 2 in 31%
      vs 69%) than those with an ileal conduit. Mean age and the percent of American
      Society of Anesthesiologists class 3 or 4 cases increased during the study.
      Neobladder represented 47% of urinary diversions in 2000 and 21% in 2005. On
      multivariate analysis age (p <0.001), gender (p = 0.004), surgery year (p =
      0.002), American Society of Anesthesiologists class greater than 2 (p = 0.004),
      organ confined disease (p = 0.01) and surgeon (p <0.001) independently predicted
      diversion choice. Patients were dichotomized into young (younger than 65 years)
      and old (65 years old or older) groups. Overall 59% of younger and 26% of older
      patients received a neobladder (p <0.001). CONCLUSIONS: There was a significant
      trend toward the more liberal use of ileal conduit urinary diversion. Patients
      with female gender, advanced age, significant medical comorbidity or locally
      advanced disease were less likely to undergo neobladder urinary diversion. This
      trend is partly explained by surgeon preference combined with an aging, more
      comorbid patient population. Neobladder continues to be the most commonly
      performed urinary diversion in patients younger than 65 years.

PMID- 19758614
TI  - Natural history of persistently elevated prostate specific antigen after radical
      prostatectomy: results from the SEARCH database.
AB  - PURPOSE: We examined natural history, predictors of biochemical recurrence and
      all cause mortality in patients with persistently elevated prostate specific
      antigen after radical prostatectomy in the Shared Equal Access Regional Cancer
      Hospital cohort. MATERIALS AND METHODS: We reviewed data on 1,156 men treated
      with radical prostatectomy after 1997. Prostate specific antigen persistence was
      defined as failure to achieve prostate specific antigen less than 0.03 ng/ml
      within 6 months postoperatively. Disease-free and overall survival was compared
      between men with and without persistence using the log rank test. Predictors of
      biochemical recurrence and all cause death were analyzed using the Cox model.
      RESULTS: A total of 291 men (25%) had persistence, which was associated with
      increased biochemical recurrence and all cause death (p <0.001 and 0.041,
      respectively). In patients with persistence 1 and 5-year biochemical recurrence
      free survival was 68% and 36%, significantly lower than 95% and 72%,
      respectively, in men without persistence. Ten-year overall survival in patients
      with vs without persistence was 63% vs 80%. In men with persistence independent
      predictors of prostate specific antigen recurrence were higher prostate specific
      antigen nadir (HR 2.19, p <0.001), positive surgical margins (HR 1.75, p = 0.022)
      and high pathological Gleason score (8-10 vs 2-6 HR 2.40, p = 0.026). Independent
      predictors of overall mortality were a higher prostate specific antigen nadir (HR
      1.46, p = 0.013) and seminal vesicle invasion (HR 3.15, p = 0.047). CONCLUSIONS:
      Prostate specific antigen persistence is associated with increased biochemical
      recurrence and overall mortality. In men with persistence the prostate specific
      antigen nadir is an independent predictor of recurrence and mortality. Thus,
      prostate specific antigen persistence and nadir are important tools for early
      postoperative risk stratification.

PMID- 19758615
TI  - Prognostic impact of histological subtype on surgically treated localized renal
      cell carcinoma.
AB  - PURPOSE: Despite the clear demonstration that different histological subtypes of
      renal cell carcinoma show distinct pathogenesis and genetic alterations, the
      impact of histology on prognosis remains controversial. We evaluated our
      experience with tumor histology in patients with localized renal cell carcinoma.
      MATERIALS AND METHODS: We identified 1,863 patients with localized clear cell,
      papillary or chromophobe renal cell carcinoma who were treated surgically between
      1989 and 2006 at our tertiary care center. Cox proportional hazards regression
      models were used to evaluate the relationship between tumor histology and
      outcome, defined as metastasis or death from disease, adjusting for age, sex,
      operation type, American Society of Anesthesiologists score, TNM stage and tumor
      size. RESULTS: Of 1,863 patients 1,333 (72%) had clear cell histology, and 310
      (17%) and 220 (12%) had papillary and chromophobe renal cell carcinoma,
      respectively. Median followup in patients without an event was 3.4 years. On
      univariate analysis patients with clear cell histology had a worse clinical
      outcome. Five-year probability of freedom from metastasis or death from disease
      was 86% (95% CI 84, 88), 95% (95% CI 91, 97) and 92% (95% CI 85, 96) in patients
      with clear cell, papillary and chromophobe histology, respectively (p <0.001). On
      multivariate analysis chromophobe (HR 0.40; 95% CI 0.20, 0.80) and papillary (HR
      0.62; 95% CI 0.34, 1.14) histology was also significantly associated with better
      outcome (p = 0.014). CONCLUSIONS: Clear cell histology seems to be independently
      associated with worse outcomes in patients who undergo surgery for renal cell
      carcinoma even after controlling for widely accepted factors influencing
      prognosis.

PMID- 19758616
TI  - Men older than 70 years have higher risk prostate cancer and poorer survival in
      the early and late prostate specific antigen eras.
AB  - PURPOSE: We clarified whether men older than 70 years have a higher risk of
      prostate cancer and poorer survival in the early and late prostate specific
      antigen eras. MATERIALS AND METHODS: A cohort of 4,561 men who underwent radical
      prostatectomy were stratified into 3 age groups (younger than 60, 60 to 70 and
      older than 70 years), and early and late prostate specific antigen eras based on
      the year of surgery (before 2000 and 2000 or later). Race, body mass index,
      prostate specific antigen, prostate weight, tumor volume, pathological Gleason
      sum, pathological tumor stage, extracapsular extension, seminal vesicle invasion
      and surgical margin status were submitted for univariate and multivariable
      analyses against the previously mentioned groups. Survivals (prostate specific
      antigen recurrence, distant metastasis and disease specific death) were compared
      among the 3 age groups using univariate and multivariable methods. RESULTS:
      Compared with younger age groups (younger than 60, 60 to 70 years) men older than
      70 years had a higher proportion of pathological tumor stage 3/4 (33.0 vs 44.3 vs
      52.1%, p <0.001), pathological Gleason sum greater than 7 (9.5% vs 13.4% vs
      17.2%, p <0.001) and larger tumor volume (3.7 vs 4.7 vs 5.2 cc, p <0.001).
      Pathological Gleason sum in men older than 70 years did not differ between the
      early and late prostate specific antigen eras (p = 0.071). Men older than 70
      years had a higher risk of prostate specific antigen recurrence, distant
      metastasis and disease specific death on univariate (p <0.05) but not
      multivariable analysis. CONCLUSIONS: Men older than 70 years had higher risk
      disease and poorer survival in the early and late prostate specific antigen eras.
      Pathological Gleason sums did not change between the 2 eras. Patient age was an
      important variable in prostate specific antigen screening, biopsy, treatment and
      prognosis.

PMID- 19758617
TI  - Editorial comment.

PMID- 19758618
TI  - Intravenous zoledronic acid to prevent osteoporosis in a veteran population with
      multiple risk factors for bone loss on androgen deprivation therapy.
AB  - PURPOSE: Androgen deprivation therapy for prostate cancer is associated with
      osteoporosis and increased fracture risk. Previous studies of zoledronic acid
      demonstrated bone loss prevention in patients initiating androgen deprivation
      therapy. There are limited data on patients on prolonged androgen deprivation
      therapy or in Veterans Affairs patients with multiple risk factors for
      osteoporosis. METHODS: We randomized 93 patients with M0 prostate cancer in this
      placebo controlled trial in the Veterans Affairs health care system. Preplanned
      strata included 50 patients on androgen deprivation therapy for less than 1 year
      (stratum 1) and 43 on androgen deprivation therapy for greater than 1 year
      (stratum 2). In each stratum patients were randomized to 4 mg zoledronic acid
      intravenously every 3 months for 4 treatments or intravenous placebo. The primary
      end point was the percent change in bone mineral density at the lumbar spine at
      12 months. RESULTS: Age, race, body mass index and osteoporosis risk factors were
      similar for the 2 treatments. Most patients were former smokers, had moderate
      alcohol intake, were not on calcium/vitamin D supplements and were relatively
      sedentary at baseline. In stratum 1 spine bone mineral density increased 5.95% in
      the zoledronic acid arm and decreased 3.23% in the placebo arm (p = 0.0044). In
      stratum 2 spine bone mineral density increased 6.08% in the zoledronic acid arm
      and only increased 1.57% in the placebo arm (p = 0.0005). Treatment was well
      tolerated with minimal impact on renal function. CONCLUSIONS: Zoledronic acid
      improved bone mineral density in patients with M0 prostate cancer on androgen
      deprivation therapy for 1 year or less, or greater than 1 year. This finding
      indicates that bisphosphonate therapy remains effective when initiated later in
      the course of androgen deprivation therapy and is efficacious in Veterans Affairs
      patients with multiple risk factors for osteoporosis.

PMID- 19758620
TI  - Exercise and prostate cancer risk in a cohort of veterans undergoing prostate
      needle biopsy.
AB  - PURPOSE: Epidemiological and molecular evidence suggest potential associations
      between exercise and prostate cancer risk reduction. We further characterized
      this relationship by examining exercise and cancer risk among men undergoing
      prostate needle biopsy. MATERIALS AND METHODS: A total of 190 men who underwent
      prostate biopsy at the Durham Veterans Affairs Medical Center completed a
      questionnaire on current exercise behavior. Participants were asked average
      frequency of mild, moderate and strenuous intensity exercise in a typical week,
      as well as average duration as assessed by the Godin Leisure Time Exercise
      Questionnaire. Total current exercise was calculated in terms of metabolic
      equivalent task hours per week. Primary outcome measures were prostate biopsy
      result and Gleason sum. RESULTS: After adjusting for age, race, body mass index,
      prostate specific antigen, digital rectal examination, family history, previous
      prostate biopsy and comorbidity score, men who reported 9 or more metabolic
      equivalent task hours per week of exercise were significantly less likely to have
      cancer on biopsy (OR 0.35, CI 0.17-0.75, p = 0.007). Furthermore, among men with
      malignant biopsy results, reporting moderate exercise (3 to 8.9 metabolic
      equivalent task hours weekly) was associated with a lower risk of high grade
      disease (Gleason 7 or greater, OR 0.14, CI 0.02-0.94, p = 0.04). CONCLUSIONS: To
      our knowledge these results provide the first evidence of an association between
      exercise and prostate cancer risk as well as grade at diagnosis in men scheduled
      to undergo prostate biopsy. Specifically moderate exercise was associated with a
      lower risk of prostate cancer and in men with cancer, lower grade disease.
      Further investigation using an objective measure of exercise in a larger sample
      size is required to confirm these findings.

PMID- 19758621
TI  - Predicting nonmuscle invasive bladder cancer recurrence and progression in
      patients treated with bacillus Calmette-Guerin: the CUETO scoring model.
AB  - PURPOSE: Bacillus Calmette-Guerin is the most effective therapy for nonmuscle
      invasive bladder cancer. Recently to calculate the risks of recurrence and
      progression based on data from 7 European Organisation for Research and Treatment
      of Cancer trials a scoring system was reported. However, in that series only 171
      patients were treated with bacillus Calmette-Guerin. We developed a risk
      stratification model to provide accurate estimates of recurrence and progression
      probability after bacillus Calmette-Guerin. MATERIALS AND METHODS: Data were
      analyzed on 1,062 patients treated with bacillus Calmette-Guerin and included in
      4 Spanish Urological Club for Oncological Treatment trials. Stepwise multivariate
      Cox models were used to determine the effect of prognostic factors. In each
      patient the weight of all factors was summed to a total score. Patients were then
      divided into groups, and cumulative recurrence and progression rates were
      calculated. RESULTS: A scoring system was calculated with a score of 0 to 16 for
      recurrence and 0 to 14 for progression. Patients were categorized into 4 groups
      by score, and recurrence and progression probabilities were calculated in each
      group. For recurrence the variables were gender, age, grade, tumor status,
      multiplicity and associated Tis. For progression the variables were age, grade,
      tumor status, T category, multiplicity and associated Tis. For recurrence
      calculated risks using Spanish Urological Club for Oncological Treatment tables
      were lower than those obtained with Sylvester tables. For progression
      probabilities were lower in our model only in patients with high risk tumors.
      CONCLUSIONS: We propose a scoring model to stratify the risk of recurrence and
      progression in patients treated with bacillus Calmette-Guerin.

PMID- 19758623
TI  - Clinical outcomes and recurrence predictors of lymph node positive urothelial
      cancer after cystectomy.
AB  - PURPOSE: Lymph node metastasis in patients who undergo radical cystectomy for
      bladder transitional cell carcinoma is considered a poor prognostic factor.
      However, patients with minimal lymph node involvement likely have a better
      outcome than those with extensive disease. We examined outcomes in patients with
      low volume lymph node metastasis and identified variables associated with disease
      recurrence. MATERIALS AND METHODS: Our institution maintains a database of 1,600
      patients with bladder transitional carcinoma who underwent radical cystectomy
      from 1971 to 2005 with intent to cure. All patients with low volume lymph node
      metastasis, defined as 1 or 2 positive lymph nodes, without concomitant distant
      metastasis were included in study. RESULTS: A total of 181 patients were
      identified. Median followup was 12.8 years, during which 96 patients experienced
      recurrence. Estimated 5 and 10-year recurrence-free survival was 43.8% and 40.9%,
      respectively. Multivariate analysis indicated that pathological stage/subgroup
      (RR 1.733, p = 0.015), lymph node density (RR 1.935, p = 0.014) and adjuvant
      chemotherapy (RR 0.538, p = 0.004) were significant independent predictors of
      recurrence-free survival. CONCLUSIONS: A considerable proportion of patients with
      low volume lymph node metastasis in our cohort remained free of recurrence during
      followup. Extravesical tumor extension and lymph node density greater than 4%
      were associated with a higher recurrence risk and adjuvant chemotherapy was
      associated with a lower risk. Although some patients with low volume lymph node
      metastasis may be cured by surgery alone, these data support adjuvant
      chemotherapy in these patients.

PMID- 19758625
TI  - A framework for the identification of men at increased risk for prostate cancer.
AB  - PURPOSE: We assessed the risk of prostate cancer over time, and the implications
      for screening strategies and potential risk reduction approaches to provide a
      framework for clinical use of this approach concordant with the use of prostate
      specific antigen as a marker of current prostate cancer risk. MATERIALS AND
      METHODS: A comprehensive review of the relevant literature was performed. In this
      article the phrase risk of/for prostate cancer refers to the risk of developing
      prostate cancer. RESULTS: Prostate specific antigen is the single most
      significant predictive factor for identifying men at increased risk for prostate
      cancer. A suspicious digital rectal examination, a family history of prostate
      cancer, the presence of high grade prostatic intraepithelial neoplasia or
      atypical small acinar proliferation and black ethnicity are also important
      predictive factors, while larger prostate volume and a previous negative biopsy
      are negative predictors. For men of screening age (50 to 70 years) a prostate
      specific antigen of greater than 1.5 ng/ml is a marker for greater than average
      risk up to 8 years (7.5-times greater risk vs 1.5 ng/ml or less). This prostate
      specific antigen threshold for a man at above average risk can be modified by the
      presence of other predictive factors. It should be lower for men with a prostate
      volume less than 40 cc, black ethnicity or a family history of prostate cancer.
      For younger men with longer followup a lower prostate specific antigen may be
      considered. CONCLUSIONS: The risk of prostate cancer can be estimated in
      individual men primarily using prostate specific antigen, but also using prostate
      volume, previous biopsy status, family history and ethnicity. Men at increased
      risk warrant enhanced surveillance and in the future may also be candidates for
      active risk reduction strategies.

PMID- 19758626
TI  - In vitro comparison of a disposable flexible ureteroscope and conventional
      flexible ureteroscopes.
AB  - PURPOSE: We compared and evaluated the objective characteristics (deflection
      characteristics, field of view and flow rate) of a disposable flexible
      ureteroscope and 6 established, commercially available flexible ureteroscopes.
      MATERIAL AND METHODS: Six commonly used ureteroscopes, including Olympus URF-P3,
      Storz(R) 11278AU and 11274AAU, ACMI DUR-8 Elite and DUR-8, and Wolf 7331.001
      (Richard Wolf Medical Instruments, Vernon Hills, Illinois), were compared with
      the recently introduced SemiFlex Scope disposable flexible ureteroscope.
      Specifications and purchase costs were acquired from each manufacturer. The
      disposable ureteroscope consisted of a reusable eyepiece and a semiflexible shaft
      with a 3.3Fr working channel. Active tip deflection was measured with and without
      the 3Fr basket, the 365 mum laser fiber and the 3Fr forceps. The flow rate and
      field of view of each scope were evaluated. RESULTS: Active tip deflection
      (down/up) was highest in the disposable ureteroscope at 300/265 degrees. Although
      deflection was decreased by inserting the different endoscopic tools in all
      ureteroscopes, the disposable ureteroscope had the highest loss in flexion
      characteristics (35.7% down and 39.3% up). The flow rate, measured at 25 ml per
      minute in the disposable ureteroscope, was significantly lower than that of other
      ureteroscopes. The disposable ureteroscope had a 72-degree field of view,
      comparable to the optical characteristics of the other scopes. Compared to the
      other 6 flexible ureteroscopes the purchase price of the disposable scope was
      significantly lower and no further maintenance/repair expenses were required.
      CONCLUSIONS: The disposable flexible ureteroscope has acceptable active tip
      deflection, field of view and flow rate compared to those of other flexible
      ureteroscopes on the market. Further evaluation of surgical outcomes will help
      delineate the definitive usefulness of the disposable flexible ureteroscope.

PMID- 19758628
TI  - A novel approach to using matrix metalloproteinases for bladder cancer.
AB  - PURPOSE: Given the steadily growing cancer survivor population, increasing
      pressure has been placed on more effective clinical approaches and biomarker
      assays to manage care. For bladder cancer despite the high probability of
      recurrence the number of patients with recurrent disease is significantly lower
      than the number that remains cancer free at any monitoring interval. We developed
      a noninvasive urine assay using a novel approach to identify patients without
      recurrent cancer with extremely high confidence. MATERIALS AND METHODS: Previous
      studies show that matrix metalloproteinases are increased in the urine of
      patients with cancer compared to that in disease-free individuals. To determine
      the clinical usefulness of these markers as monitors for bladder cancer
      recurrence we measured and compared metalloproteinase-2, metalloproteinase-9 and
      metalloproteinase-9/neutrophil gelatinase-associated lipocalin by enzyme-linked
      immunosorbent assay and zymography in a set of 530 samples, including 84 samples
      from patients with bladder cancer. RESULTS: Initial studies using urine
      metalloproteinase to discriminate disease-free patients from those with bladder
      cancer resulted in 80% sensitivity (67 of 84) and 71% specificity (318 of 446)
      for metalloproteinase-9. By applying our novel Clinical Intervention Determining
      Diagnostic() clinical approach to metalloproteinase-9 we correctly identified 42%
      of cases that were cystoscopy negative with 98% negative predictive value.
      CONCLUSIONS: A noninvasive urine diagnostic assay that uses metalloproteinases
      with the Clinical Intervention Determining Diagnostic could lead to more
      efficient treatment in bladder cancer survivors by decreasing the number of
      negative cystoscopies (42%), allowing physicians to more selectively monitor
      those at high risk.

PMID- 19758629
TI  - The urothelial glycosaminoglycan layer revisited.

PMID- 19758630
TI  - Editorial comment.

PMID- 19758631
TI  - Validating the incontinence symptom severity index: a self-assessment instrument
      for voiding symptom severity in women.
AB  - PURPOSE: Most voiding symptom self-assessment instruments assess either symptom
      bother or effect on quality of life. The Incontinence Symptom Severity Index is
      an instrument for self-assessment of severity of female urinary storage and
      voiding symptoms, rather than symptom bother or effects of symptoms on quality of
      life. We assessed the validity of the Incontinence Symptom Severity Index for
      female voiding symptom self-assessment. MATERIALS AND METHODS: The Incontinence
      Symptom Severity Index assesses 8 symptom domains, including emptying, urgency,
      urge incontinence, nocturia, daytime frequency, stress incontinence, leakage with
      physical activity and pad use. Three separate cohorts of women with a mean age of
      59, 60 and 63 years, respectively, who underwent evaluation for urinary
      complaints associated with incontinence and vaginal prolapse were analyzed.
      Internal consistency was assessed via item-total correlations and Cronbach's
      alpha. Concurrent validity against the Urogenital Distress Inventory and Pelvic
      Floor Distress Inventory-Short Form were studied by correlating similar symptom
      domains of the Incontinence Symptom Severity Index with both instruments. We
      assessed criterion validity by comparison with the objective measures of post
      void residual urine, voiding logs and self-reported pad use. Response to change
      was assessed by comparing pretreatment and posttreatment Incontinence Symptom
      Severity Index scores. RESULTS: Significant item total correlations were seen for
      each Incontinence Symptom Severity Index item and Cronbach's alpha was 0.69. All
      Incontinence Symptom Severity Index items significantly correlated with similar
      items of the Urogenital Distress Inventory and Pelvic Floor Distress Inventory
      Short Form. Significant posttreatment reductions were also observed for all 8
      Incontinence Symptom Severity Index items. Progressively higher post-void
      residual urine was noted for the 4 severity scores of Incontinence Symptom
      Severity Index item 1 (emptying) (p = 0.07). Incontinence Symptom Severity Index
      items 3 (nocturia) and 4 (daytime frequency) showed significantly increasing
      nighttime and daytime voids with worsening severity scores for each (p <0.0001
      and <0.0041, respectively). Incontinence Symptom Severity Index items 5 to 8
      (stress incontinence, urge incontinence, leakage with activity and pad use)
      showed significantly increasing trends in mean daily pad use (p <0.0001, 0.022,
      <0.0001 and <0.0001, respectively) among the 4 severity scores for each.
      CONCLUSIONS: The Incontinence Symptom Severity Index demonstrates good
      reliability and validity. It is a useful instrument for assessment of female
      incontinence and voiding symptom severity in clinical and research settings.

PMID- 19758632
TI  - Editorial comment.

PMID- 19758634
TI  - Editorial comment.

PMID- 19758633
TI  - Evidence for overlap between urological and nonurological unexplained clinical
      conditions.
AB  - PURPOSE: Unexplained clinical conditions share common features such as pain,
      fatigue, disability out of proportion to physical examination findings,
      inconsistent laboratory abnormalities, and an association with stress and
      psychosocial factors. We examined the extent of the overlap among urological and
      nonurological unexplained clinical conditions characterized by pain. We describe
      the limitations of previous research and suggest several possible explanatory
      models. MATERIALS AND METHODS: Using hallmark symptoms and syndromes as search
      terms a search of 12 databases identified a total of 1,037 full-length published
      articles in 8 languages from 1966 to April 2008. The search focused on the
      overlap of chronic pelvic pain, interstitial cystitis, painful bladder syndrome,
      chronic prostatitis/chronic pelvic pain syndrome or vulvodynia with fibromyalgia,
      chronic fatigue syndrome, temporomandibular joint and muscle disorders or
      irritable bowel syndrome. We abstracted information on authorship, type of case
      and control groups, eligibility criteria, case definitions, study methods and
      major findings. RESULTS: The literature suggests considerable comorbidity between
      urological and nonurological unexplained clinical conditions. The most robust
      evidence for overlap was for irritable bowel syndrome and urological unexplained
      syndromes with some estimates of up to 79% comorbidity between chronic pelvic
      pain and symptoms of irritable bowel syndrome. However, most studies were limited
      by methodological problems, such as varying case definitions and selection of
      controls. CONCLUSIONS: The overlap between urological and selected nonurological
      unexplained clinical conditions is substantial. Future research should focus on
      using standardized definitions, and rigorously designed, well controlled studies
      to further assess comorbidity, clarify the magnitude of the association and
      examine common pathophysiological mechanisms.

PMID- 19758635
TI  - Radical prostatectomy findings in patients in whom active surveillance of
      prostate cancer fails.
AB  - PURPOSE: Little data are available on radical prostatectomy findings in men who
      experience disease progression following active surveillance. MATERIALS AND
      METHODS: A total of 470 men in our active surveillance program underwent annual
      repeat needle biopsies to look for progression defined as any Gleason pattern
      grade 4/5, more than 50% cancer on any core or cancer in more than 2 cores.
      Slides were available for review in 48 of 51 radical prostatectomies with
      progression. RESULTS: The average time between the first prostate biopsy and
      radical prostatectomy was 29.5 months (range 13 to 70), with 44% and 75% of the
      patients showing progression by the second and third biopsy, respectively. There
      were 31 (65%) organ confined cases, of which 25 (52%) were Gleason score 6. Of 48
      cases 17 (35%) had extraprostatic extension, 3 had seminal vesicle/lymph node
      involvement and 7 (15%) had positive margins. Mean total tumor volume was 1.3
      cm(3) (range 0.02 to 10.8). Of the 48 tumors 13 (27%) were potentially clinically
      insignificant (organ confined, dominant nodule less than 0.5 cm(3), no Gleason
      pattern 4/5) and 19% (5 of 26) of the radical prostatectomies with a dominant
      tumor nodule less than 0.5 cm(3) demonstrated extraprostatic extension, 4 with
      Gleason pattern 4. All 10 tumors with a dominant nodule greater than 1 cm(3) were
      located predominantly anteriorly. CONCLUSIONS: Most progression after active
      surveillance occurs 1 to 2 years after diagnosis suggesting undersampling of more
      aggressive tumor rather than progression of indolent tumor. Even with progression
      most tumors have favorable pathology (27% potentially insignificant). A small
      percentage of men have advanced stage disease (pT3b or N1). The anterior region
      should be sampled in men on active surveillance.

PMID- 19758636
TI  - Should testosterone replacement be given to men with large prostates?

PMID- 19758637
TI  - Editorial comment.

PMID- 19758638
TI  - Pathological stage T2 subgroups to predict biochemical recurrence after
      prostatectomy.
AB  - PURPOSE: We evaluated whether the 2002 TNM substages of pathological T2 prostate
      cancer predict intermediate term biochemical recurrence-free survival. MATERIALS
      AND METHODS: The cohort consisted of men who underwent radical prostatectomy
      between January 2000 and June 2008, and had pT2 disease at final pathological
      evaluation. We excluded patients with prior treatment, less than 6 months of
      followup or missing data, leaving 1,370 available for analysis, including 340
      with pT2a, 35 with pT2b and 995 with pT2c disease. Clinical and pathological
      characteristics were compared between groups using univariate analysis.
      Biochemical recurrence-free survival was compared between substages using Kaplan
      Meier analysis. A Cox proportional hazards model was used to evaluate tumor
      substage as a biochemical recurrence-free survival predictor. RESULTS: Median
      followup was 21 months. No differences were seen in the likelihood of biochemical
      recurrence-free survival between T2 subclasses (p = 0.174). No patient with T2b
      disease had recurrence. The 3 and 5-year likelihood of freedom from biochemical
      recurrence was 95.5% (95% CI 90.9-97.8) and 93.8% (95% CI 87.3-97.0) for pT2a,
      and 94.3% (95% CI 91.8-96.0) and 87.5% (95% CI 82.7-91.1) for pT2c, respectively.
      Multivariate analysis showed that significant predictors of biochemical
      recurrence-free survival were margin status (HR 2.7, 95% CI 1.3-5.5, p = 0.006),
      preoperative prostate specific antigen (HR 1.0, 95% CI 1.0-1.1, p = 0.029),
      pathological Gleason score 7 (HR 2.5, 95% CI 1.1-5.7, p = 0.024) and pathological
      Gleason score 8-10 (HR 6.2, 95% CI 2.2-17.4, p <0.001). Compared to pathological
      stage T2a neither pT2b nor pT2c predicted biochemical recurrence-free survival (p
      = 0.99 and 0.42, respectively). CONCLUSIONS: Current pT2 prostate cancer
      substages may not have prognostic significance for intermediate term outcomes. If
      borne out during longer followup, future staging systems may collapse the
      substages into a single category.

PMID- 19758639
TI  - Impact of urine sodium on urine risk factors for calcium oxalate nephrolithiasis.
AB  - PURPOSE: Increased sodium intake is thought to promote nephrolithiasis by dietary
      sodium hypercalciuric effects. However, equivocal data exist on whether increased
      urine sodium actually increases the nephrolithiasis risk. We examined the
      relationship between urine sodium and urine risk factors for nephrolithiasis.
      MATERIALS AND METHODS: We retrospectively reviewed the records of 880 patients
      evaluated at a metabolic stone clinic to determine the relationship between urine
      sodium and urine calcium, volume and calcium oxalate supersaturation. Patients
      were separated into sodium excretion quintiles. Tests of linear trend were
      performed by examining the linear contrast in coefficients and using Cuzick's
      nonparametric linear trend test. Multivariate linear regression with urine sodium
      as a continuous variable was done to assess the relationship between urine sodium
      and other urine variables. RESULTS: Tests of linear trend showed that urine
      calcium and volume increased with increasing urine sodium (each p <0.01) but
      urine calcium oxalate supersaturation decreased with increasing urine sodium (p
      <0.01). Multivariate linear regression was adjusted for age, sex, body mass index
      and urine constituents. Urine sodium was positively associated with urine calcium
      (beta = 0.28, 95% CI 0.15 to 0.41, p <0.001) but negatively associated with urine
      calcium oxalate supersaturation (beta = -0.013, 95% CI -0.016 to -0.011, p
      <0.001). There was a trend toward a positive association of urine sodium and
      volume (beta = 0.001, 95% CI -0.00019 to 0.002, p = 0.10). CONCLUSIONS:
      Increasing urine sodium does not appear to increase the risk of calcium oxalate
      nephrolithiasis. Global sodium restriction may not necessarily alter the risk of
      stone formation, ie cause changes in calcium oxalate urine supersaturation, in
      patients with a history of nephrolithiasis.

PMID- 19758640
TI  - Do we need more rigorous standards for validation of new technology?

PMID- 19758641
TI  - Cytoreductive nephrectomy for kidney cancer with sarcomatoid histology--is up
      front resection indicated and, if not, is it avoidable?
AB  - PURPOSE: Cytoreductive nephrectomy has a survival advantage in select patients.
      Patients with sarcomatoid features are known to have poor outcomes. We reviewed
      the role of surgery in this population to see if these patients could be
      identified preoperatively. MATERIALS AND METHODS: Cytoreductive nephrectomy cases
      identified as having sarcomatoid features or spindle cells were reviewed. The
      histology, grade, and the presence and percentage of sarcomatoid elements were
      recorded. Clinicopathological characteristics, survival and systemic therapy were
      compared to cases without sarcomatoid histology. RESULTS: A total of 62 tumors
      with sarcomatoid histology were identified, accounting for 14.9% of the 417
      patients undergoing cytoreductive nephrectomy. The percentage of sarcomatoid
      transformation widely varied with a range of 2% to 100% and a mean/median of
      49.8%/50%. An increased percentage of sarcomatoid features is associated with a
      worse prognosis. Patients with and those without sarcomatoid features had similar
      clinical characteristics. In the sarcomatoid group a higher T stage (p <0.001)
      and increased incidence of nonclear cell histology (p <0.001) were noted. Median
      survival of patients with sarcomatoid features was 4.9 vs 17.7 months for
      nonsarcomatoid histology (p <0.001). Use of postoperative therapy was
      significantly worse for patients with sarcomatoid histology. CONCLUSIONS:
      Patients with sarcomatoid histology undergoing cytoreductive nephrectomy have a
      dire prognosis despite aggressive surgery and postoperative therapy. The
      variability in the sarcomatoid component and the lack of specific clinical
      features make preoperative identification challenging. Research should focus on
      identifying biomarkers for this subset of tumors that may allow up-front systemic
      therapy with surgery reserved for responding patients.

PMID- 19758642
TI  - Editorial comment.

PMID- 19758643
TI  - Editorial comment.

PMID- 19758644
TI  - Editorial comment.

PMID- 19758645
TI  - Can men reduce the risk of prostate cancer through lifestyle changes?

PMID- 19758646
TI  - Lack of an effect of high dose isoflavones in men with prostate cancer undergoing
      androgen deprivation therapy.
AB  - PURPOSE: The profound hypogonadism due to androgen deprivation therapy for
      prostate cancer results in complications such as sexual dysfunction, poor quality
      of life, vasomotor symptoms and altered cognition. Since estrogen is associated
      with cardiovascular risks, phytoestrogens are being increasingly evaluated as a
      potential treatment for these adverse effects. We evaluated the effects of high
      dose isoflavones, equivalent to that consumed by Asian populations, on the
      aforementioned consequences of androgen deprivation therapy. MATERIALS AND
      METHODS: A total of 33 men undergoing androgen deprivation therapy for prostate
      cancer were enrolled in this randomized, double-blind, placebo controlled, 12
      week pilot trial. Participants were randomly assigned to receive 20 gm soy
      protein containing 160 mg total isoflavones (17) vs taste matched placebo, that
      is 20 gm whole milk protein (16). The study was performed at a tertiary care
      center in the United States. RESULTS: At baseline the groups were well matched in
      demographic parameters, sleep quality, cognition and overall quality of life.
      However, men in the isoflavone group had a higher baseline prevalence of hot
      flashes and poor intercourse satisfaction compared to those on placebo. At 12
      weeks there were no significant differences between the 2 groups in any outcome
      measure. CONCLUSIONS: This pilot study of high dose isoflavones in androgen
      deprived men showed no significant improvement in cognition, vasomotor symptoms
      or any other aspect of quality of life measures compared to placebo. Future
      studies should use variable doses of isoflavones for a longer period before
      ruling out beneficial isoflavone effects in this population.

PMID- 19758647
TI  - Editorial comment.

PMID- 19758648
TI  - Gastric bypass procedures and renal calculi--how should we counsel patients and
      bariatric surgeons?

PMID- 19758650
TI  - Editorial comment.

PMID- 19758651
TI  - Laparoscopic radical nephrectomy for renal cell carcinoma: oncological outcomes
      at 10 years or more.
AB  - PURPOSE: We present oncological outcomes at a followup of 10 years or greater
      after laparoscopic radical nephrectomy for cancer. MATERIALS AND METHODS: Between
      February 1994 and March 1999 a total of 73 laparoscopic radical nephrectomies
      were performed by 2 surgeons for pathologically confirmed renal cell carcinoma.
      Data were obtained from patient charts, radiographic reports, telephone followup
      and a check of the Social Security Death Index. RESULTS: Mean followup was 11.2
      years (range 10 to 15). Each patient completed a minimum 10-year followup. Mean
      patient age at surgery was 60 years. Mean tumor size on computerized tomography
      was 5 cm (range 1.7 to 13). Pathological stage was pT1a in 41% of cases, pT1b in
      30%, pT2 in 15%, pT3a in 10%, pT3b in 3% and pT4 in 1%. High grade tumors
      (Fuhrman 3 or greater) were present in 18 cases (28%). A positive surgical margin
      occurred in 1 case. Actual 10-year overall, cancer specific and recurrence-free
      survival rates were 65%, 92% and 86%, respectively. Overall, cancer specific and
      recurrence-free survival rates at 12 years were 35%, 78% and 77%, respectively.
      At a mean of 67 months 10 patients (14%) had metastatic disease, of whom 8 (11%)
      died. CONCLUSIONS: Long-term oncological outcomes after laparoscopic radical
      nephrectomy for renal cell carcinoma are excellent and appear comparable to those
      of open surgery.

PMID- 19758652
TI  - Editorial comment.

PMID- 19758653
TI  - Editorial comment.

PMID- 19758654
TI  - Editorial comment.

PMID- 19758655
TI  - Minimally invasive nephron sparing management for renal tumors in solitary
      kidneys.
AB  - PURPOSE: We present a large series of minimally invasive nephron sparing surgery
      outcomes in solitary kidneys with a focus on treatment selection criteria, and
      oncological and functional outcomes. MATERIALS AND METHODS: Of 1,019 patients who
      underwent minimally invasive nephron sparing surgery since September 1997 at our
      institution 36, 36 and 29 underwent laparoscopic partial nephrectomy,
      cryoablation and radio frequency ablation, respectively, for tumors in a solitary
      kidney. Data, including patient and tumor characteristics, surgery details,
      complications, and postoperative renal function and intermediate term oncological
      outcomes in each patient, were obtained by telephone contact or from charts. The
      3 groups were compared for perioperative, functional and oncological outcomes.
      RESULTS: On multivariate analysis tumor size, aspect and remnant kidney status
      were independent predictors of treatment selection. Cancer specific and overall
      survival at 2 years was 100% and 91.2% for laparoscopic partial nephrectomy,
      88.5% and 88.5% for cryoablation, and 83.9% and 83.9% for radio frequency
      ablation, respectively. Disease-free survival was significantly better for
      laparoscopic partial nephrectomy than for cryoablation and radio frequency
      ablation (100% vs 69.6% and 33.2%, respectively, p <0.0001). The mean estimated
      glomerular filtration rate change for laparoscopic partial nephrectomy,
      cryoablation and radio frequency ablation of 17, 3 and 7 ml per minute per 1.73
      m(2) reflected a 26%, 6% and 13% decrease from baseline, respectively, which was
      statistically significant (p = 0.0016). CONCLUSIONS: Laparoscopic partial
      nephrectomy and probe ablative procedures can be safely and efficiently done for
      renal tumor in patients with a solitary kidney. Intermediate term oncological
      outcomes are superior for laparoscopic partial nephrectomy despite somewhat
      poorer renal function outcomes than those of cryoablation and radio frequency
      ablation.

PMID- 19758657
TI  - Prostate cancer early detection program recruitment methods and show rates in men
      at high risk.
AB  - PURPOSE: Men with a family history of prostate cancer and black men are at higher
      risk for prostate cancer. Recruitment and retention of these men at high risk
      into early detection programs is challenging. We report a comprehensive analysis
      of recruitment methods, show rates and participant factors from the Prostate
      Cancer Risk Assessment Program, a prospective, longitudinal prostate cancer
      screening study. MATERIALS AND METHODS: Men 35 to 69 years old were eligible for
      recruitment if they had a family history of prostate cancer, were black or had a
      BRCA1/2 mutation. Recruitment methods were analyzed using standard statistical
      methods with respect to participant demographics and presentation to the first
      program appointment. RESULTS: Of 707 men recruited 64.9% presented to the initial
      program appointment. More men were recruited via radio than via referral or other
      methods (chi-square = 298.13, p <0.0001). Men recruited by radio were more likely
      to be black (p <0.001), less educated (p = 0.003) and not married or partnered (p
      = 0.007), and have no prostate cancer family history (p <0.001). Men recruited by
      referral had a higher income (p = 0.007) and were more likely to attend the
      initial program visit than those recruited by radio or other methods (chi-square
      = 27.08, p <0.0001). CONCLUSIONS: This comprehensive analysis shows that radio
      led to higher recruitment of black men with lower socioeconomic status. However,
      these men at high risk have a lower presentation rate for prostate cancer
      screening. Targeted motivational measures must be studied to improve the show
      rate for prostate cancer risk assessment in these men at high risk.

PMID- 19758658
TI  - Prostanoid receptor subtypes: new targets for OAB drugs?

PMID- 19758659
TI  - Partial nephrectomy after previous radio frequency ablation: the National Cancer
      Institute experience.
AB  - PURPOSE: Development of new renal tumors or recurrence after radio frequency
      ablation not amendable for repeat ablation presents a difficult therapeutic
      dilemma. We report on the outcomes of partial nephrectomy on kidneys previously
      treated with radio frequency ablation. MATERIALS AND METHODS: We performed a
      chart review of 13 patients who underwent 16 attempted partial nephrectomies
      following radio frequency ablation. Hospital records and operative reports were
      reviewed for demographic data, perioperative data and outcomes. The outcomes of
      the present series were compared to historical controls of published studies in
      similar patient populations. RESULTS: No cases were converted to radical
      nephrectomy. Median time from radio frequency ablation to surgery was 2.75 years
      (range 1 to 7.1). A median of 7 tumors (range 2 to 40) were removed with a median
      estimated blood loss of 1,500 ml (range 500 to 3,500) and a median operative time
      of 7.8 hours (range 5 to 10.7). Operative notes commented on the presence of
      severe fibrosis in the operative field in 12 of 16 cases (75%). There was a
      modest but statistically significant decrease in renal function. Partial
      nephrectomy after radio frequency ablation had a higher reoperation rate compared
      to other series of primary or repeat partial nephrectomies but had the lowest
      rate of vascular or visceral injuries. CONCLUSIONS: Partial nephrectomy on
      kidneys previously treated with radio frequency ablation is a technically
      challenging but feasible procedure. Residual or metachronous disease after radio
      frequency ablation may be salvaged with partial nephrectomy with a modest
      decrease in renal function. A trend toward a higher chance of reoperation and
      urine leak after partial nephrectomy after radio frequency ablation may be useful
      information for the planning and discussion of treatment decisions.

PMID- 19758660
TI  - The expression of thrombospondin-1 and p53 in clear cell renal cell carcinoma:
      its relationship to angiogenesis, cell proliferation and cancer specific
      survival.
AB  - PURPOSE: We evaluated possible associations among thrombospondin-1, p53
      expression, microvessel density, cell proliferation index, nuclear grade, tumor
      stage and continuously coded tumor size in clear cell renal cell carcinoma. The
      value of thrombospondin-1 as a prognostic marker in clear cell renal cell
      carcinoma was examined. MATERIALS AND METHODS: A total of 172 consecutive
      patients with clear cell renal cell carcinoma treated with radical nephrectomy
      were initially enrolled in the study. However, due to technical problems and lack
      of material 12 cases were excluded from analysis. A total of 68 patients (43%)
      died of renal cell carcinoma and 46 (29%) died of other diseases. Median followup
      for the surviving 42 patients (29%) was 13.8 years. The expression of
      thrombospondin-1, Ki-67 (proliferation index), p53 and microvessel density were
      analyzed without knowledge of the clinical outcome on formalin fixed, paraffin
      embedded tissues. RESULTS: Low expression of thrombospondin-1 was significantly
      associated with advanced stage (p <0.001), high nuclear grade (p = 0.001),
      positive p53 status (p <0.001), high proliferation index (p = 0.001), high
      microvessel density (p = 0.036) and tumor progression (p = 0.006). On univariate
      analysis thrombospondin-1, microvessel density, proliferation index, p53 over
      expression, TNM stage, Fuhrman nuclear grade (p <0.001) and continuously coded
      tumor size (p = 0.002) had a significant impact on survival. Multivariate
      analysis revealed TNM stage, thrombospondin-1, p53, Ki-67 (proliferation index)
      and microvessel density were independent predictors of cancer specific survival.
      CONCLUSIONS: Thrombospondin-1 expression is strongly associated with prognostic
      tumor features in clear cell renal cell carcinoma and is an independent
      prognostic factor for cancer specific survival. Our findings revealed a
      significant correlation among p53, proliferation index, microvessel density and
      thrombospondin-1 expression, and indicate that thrombospondin-1 may have an
      impact on angiogenesis, proliferation and tumor aggressiveness in clear cell
      renal cell carcinoma.

PMID- 19758661
TI  - Reevaluation of renal cell carcinoma and perirenal fat invasion only.
AB  - PURPOSE: Controversy continues over whether perirenal fat invasion in pT3a renal
      cell carcinoma is a prognostic factor. We investigated the prognosis of renal
      cell carcinoma with perirenal fat invasion compared to the prognosis of other
      pathological stages by tumor size. MATERIALS AND METHODS: We reviewed the medical
      records of 946 patients who underwent curative surgery for pT1-pT3bN0M0 renal
      cell carcinoma between 1988 and 2006. Patients with pT3a stage disease and
      perirenal fat invasion only were divided into 2 subgroups by a 7 cm tumor size
      cutoff. The prognostic impact of perirenal fat invasion on disease-free and
      cancer specific survival was investigated. RESULTS: Patients with perirenal fat
      invasion and lesions greater than 7 cm had lower 5-year disease-free (49.5% vs
      77.2%, p = 0.004) and cancer specific (58.5% vs 95.6%, p = 0.003) survival than
      those with lesions 7 cm or less. Patients with perirenal fat invasion and lesions
      7 cm or less had similar 5-year disease-free and cancer specific survival
      compared to those with pT1 tumors (p = 0.109 and 0.602, respectively). For tumors
      7 cm or less multivariate analysis showed that perirenal fat invasion was not a
      significant predictor of disease-free (p = 0.119) or cancer specific (p = 0.208)
      survival. In contrast, perirenal fat invasion was an independent prognostic
      factor for disease-free (p = 0.002) and cancer specific (p = 0.027) survival in
      patients with tumors greater than 7 cm. CONCLUSIONS: Findings suggest that the
      prognostic significance of perirenal fat invasion depends on primary tumor size.
      Perirenal fat invasion included in the pT3a stage regardless of tumor size should
      be reevaluated by tumor size for a more accurate patient prognosis.

PMID- 19758662
TI  - Location of the primary tumor is not an independent predictor of cancer specific
      mortality in patients with upper urinary tract urothelial carcinoma.
AB  - PURPOSE: The prognostic significance of renal pelvis vs ureteral upper urinary
      tract urothelial carcinoma tumor location is controversial. We assessed the
      prognostic significance of upper urinary tract urothelial carcinoma tumor
      location in a large, population based data set. MATERIALS AND METHODS: Our
      analyses relied on 2,824 patients treated with nephroureterectomy for upper
      urinary tract urothelial carcinoma within 9 SEER registries between 1988 and
      2004. Univariable and multivariable models tested the effect of tumor location on
      cancer specific mortality rates. Covariates consisted of age, race, SEER
      registry, gender, type of surgery (nephroureterectomy with vs without bladder
      cuff removal), pT stage, pN stage, grade and year of surgery. RESULTS: Relative
      to ureteral tumors renal pelvis tumors were of higher stage (T3/T4 disease 38.4%
      vs 57.9%, p <0.001) and had a higher rate of lymph node metastases (6.0% vs 9.8%,
      p = 0.003) at nephroureterectomy. The respective 5-year cancer specific mortality
      free survival estimates were 81.0% vs 75.5% (p = 0.007). However, after
      multivariable adjustment tumor location failed to reach independent predictor
      status of cancer specific mortality (p = 0.8). CONCLUSIONS: To our knowledge this
      is the largest cohort in which the impact of upper urinary tract urothelial
      carcinoma tumor location on cancer specific mortality was examined. At
      nephroureterectomy renal pelvis tumors had significantly more advanced T and N
      stages compared to ureteral tumors. However, after adjustment for stage, grade
      and other covariates tumor location did not independently predict cancer specific
      mortality. Thus, the biological behavior of renal pelvis vs ureteral tumors is
      the same after nephroureterectomy as long as stage, grade, and other patient and
      tumor characteristics are accounted for.

PMID- 19758663
TI  - Editorial comment.

PMID- 19758664
TI  - Editorial comment.

PMID- 19758665
TI  - Temporal and spatial variability of trace metals in sediments of two adjacent
      tributaries of the Neuse River Estuary, North Carolina, USA.

PMID- 19758666
TI  - Mycorrhization alleviates benzo[a]pyrene-induced oxidative stress in an in vitro
      chicory root model.
AB  - Among chemicals that are widely spread both in terrestrial and aquatic
      ecosystems, benzo[a]pyrene is a major source of concern. However, little is known
      about its adverse effects on plants, as well as about the role of mycorrhization
      in protection of plant grown in benzo[a]pyrene-polluted conditions. Hence, to
      contribute to a better understanding of the adverse effects of polycyclic
      aromatic hydrocarbons on the partners of mycorrhizal symbiotic association,
      benzo[a]pyrene-induced oxidative stress was studied in transformed Cichorium
      intybus roots grown in vitro and colonized or not by Glomus intraradices. The
      arbuscular mycorrhizal fungus development (colonization, extraradical hyphae
      length, and spore formation) was significantly reduced in response to increasing
      concentrations of benzo[a]pyrene (35-280 microM). The higher length of arbuscular
      mycorrhizal roots, compared to non-arbuscular mycorrhizal roots following
      benzo[a]pyrene exposure, pointed out a lower toxicity of benzo[a]pyrene in
      arbuscular mycorrhizal roots, thereby suggesting protection of the roots by
      mycorrhization. Accordingly, in benzo[a]pyrene-exposed arbuscular mycorrhizal
      roots, statistically significant decreases were observed in malondialdehyde
      concentration and 8-hydroxy-2'-desoxyguanosine formation. The higher superoxide
      dismutase activity detected in mycorrhizal chicory roots could explain the
      benzo[a]pyrene tolerance of the colonized roots. Taken together, these results
      support an essential role of mycorrhizal fungi in protecting plants submitted to
      polycyclic aromatic hydrocarbon, notably by reducing polycyclic aromatic
      hydrocarbon-induced oxidative stress damage.

PMID- 19758667
TI  - [Nutcracker syndrome].

PMID- 19758668
TI  - In vitro algaecide effect of sodium hypochlorite and iodine based antiseptics on
      Prototheca zopfii strains isolated from bovine milk.
AB  - Prototheca zopfii has been considered one of the most important causes of
      environmental mastitis in Brazil. These algae are refractory to conventional
      therapy and cause great damage to the mammary gland. The present study evaluated
      the in vitro algaecide effect of sodium hypochlorite and iodine based antiseptics
      on 27 P. zopfii strains isolated from the milk of cattle. Low concentrations of
      sodium hypochlorite (0.0390625-0.15625%) and iodine (0.15625-0.625%) were
      effective against the isolates. These antiseptics may be recommended for hygiene
      routines, pre and postdipping and cauterization of bovine mammary glands infected
      by P. zopfii.

PMID- 19758669
TI  - [Fahr's syndrome: two case report].
AB  - INTRODUCTION: Fahr's syndrome is characterized by symmetrical and bilateral
      intracerebral calcifications, located in the basal ganglia and mostly associated
      with a phosphorus calcium metabolism disorder. It must be distinguished from
      genetic or sporadic Fahr's disease. OBSERVATIONS: We report two cases of this
      syndrome, the first was revealed by psychotic and cognitive disorders and the
      other by epilepsy. In both cases, brain imaging and biology resulted in the
      diagnosis of Fahr's syndrome. The outcome was favorable after treatment in both
      cases. CONCLUSION: These two observations illustrate various clinical signs of
      Fahr's syndrome.

PMID- 19758670
TI  - Dual hepatic artery reconstruction in living donor liver transplantation using a
      left hepatic graft with 2 hepatic arterial stumps.
AB  - BACKGROUND: A left hepatic graft in living donor liver transplantation (LDLT)
      often has 2 thin and short hepatic arterial stumps, which makes hepatic artery
      (HA) reconstructions much more difficult to perform. Consequently, some
      investigators regard using a left graft as a contraindication to LDLT, whereas
      others report that the reconstruction of only 1 HA is sufficient for most LDLTs.
      The aim of this retrospective study was to investigate whether 2 HAs on a left
      hepatic graft in an LDLT can be reconstructed safely and whether the outcomes of
      LDLTs are affected by reconstructing both HAs (dual reconstruction). METHODS: A
      total of 175 LDLTs using a left graft between October 1996 and April 2008 were
      divided into 3 groups: group 1 (n = 104): 1 HA stump with 1 HA reconstruction;
      group 2 (n = 47): 2 HA stumps with dual HA reconstruction; and group 3 (n = 24):
      2 HA stumps with only 1 HA reconstruction. We reconstructed HAs using
      microvascular surgical techniques. RESULTS: With technical advancement, we have
      been able to reconstruct both HAs in most cases without any HA-related
      complications, despite the fact that complex HA reconstructions were needed.
      Group 3 patients had a significantly greater incidence of anastomotic biliary
      stricture, which was decreased by dual HA reconstructions to the same level as
      observed in group 1. CONCLUSION: Dual HA reconstructions can be performed safely
      in LDLTs with a decreased incidence of anastomotic biliary stricture.

PMID- 19758671
TI  - Pneumatosis intestinalis and pneumoperitoneum during treatment by paclitaxel.

PMID- 19758672
TI  - Prognostic impact of the width of subserosal invasion in gastric cancer invading
      the subserosal layer.
AB  - BACKGROUND: The depth of wall invasion is one of the most important prognostic
      factors in patients with gastric cancers. We hypothesized that the horizontal
      width of spread of the neoplasm in the subserosal layer correlated with frequency
      of latent tumor exposure to the subserosal surface in subserosal (ss) gastric
      cancer. METHODS: We compared retrospectively the relationship between the
      horizontal width of ss invasion and other clinicopathologic factors in 124
      patients with ss cancer confirmed carefully to have T2 and not T3 neoplasms.
      Selected clinicopathologic parameters of these ss patients were compared to 134
      patients with serosal penetration (se) by gastric cancer, and 78 patients with
      invasion of the muscularis propria only (mp). RESULTS: The width of ss invasion
      was found to be an important prognostic factor on both univariate (P < .001) and
      multivariate analyses (P = .006). The prognosis of ss-cancer with narrow-width
      invasion (less than 20 mm) was similar to that of mp-cancer, while the prognosis
      of ss-cancer with wide width (more than 20 mm) was similar to that of se-cancer.
      CONCLUSION: Our findings showed that narrow-width ss-cancer (<20 mm) behaved very
      similar to mp-cancers, while wide ss-cancers (> or =20 mm) behaved very similar
      to se-cancers. These findings demonstrated the prognostic impact of the width of
      cancer invasion in subserosal layer in patients with ss-cancer. Intensive
      chemotherapy and close follow-up should be recommended for ss-cancer patients
      with greater than 20 mm involvement of the subserosal layer.

PMID- 19758673
TI  - Dual-mode transducers for ultrasound imaging and thermal therapy.
AB  - Medical imaging is a vital component of high intensity focused ultrasound (HIFU)
      therapy, which is gaining clinical acceptance for tissue ablation and cancer
      therapy. Imaging is necessary to plan and guide the application of therapeutic
      ultrasound, and to monitor the effects it induces in tissue. Because they can
      transmit high intensity continuous wave ultrasound for treatment and pulsed
      ultrasound for imaging, dual-mode transducers aim to improve the guidance and
      monitoring stages. Their primary advantage is implicit registration between the
      imaging and treatment axes, and so they can help ensure before treatment that the
      therapeutic beam is correctly aligned with the planned treatment volume. During
      treatment, imaging signals can be processed in real-time to assess acoustic
      properties of the tissue that are related to thermal ablation. Piezocomposite
      materials are favorable for dual-mode transducers because of their improved
      bandwidth, which in turn improves imaging performance while maintaining high
      efficiency for treatment. Here we present our experiences with three dual-mode
      transducers for interstitial applications. The first was an 11-MHz monoelement
      designed for use in the bile duct. It had a 25x7.5 mm(2) aperture that was
      cylindrically focused to 10mm. The applicator motion was step-wise rotational for
      imaging and therapy over a 360 degrees, or smaller, sector. The second transducer
      had 5-elements, each measuring 3.0x3.8 mm(2) for a total aperture of 3.0x20
      mm(2). It operated at 5.6 MHz, was cylindrically focused to 14 mm, and was
      integrated with a servo-controlled oscillating probe designed for sector imaging
      and directive therapy in the liver. The last transducer was a 5-MHz, 64-element
      linear array designed for beam-formed imaging and therapy. The aperture was
      3.0x18 mm(2) with a pitch of 0.280 mm. Characterization results included
      conversion efficiencies above 50%, pulse-echo bandwidths above 50%, surface
      intensities up to 30 W/cm(2), and axial imaging resolutions to 0.2 mm. The second
      transducer was evaluated in vivo using porcine liver, where coagulation necrosis
      was induced up to a depth of 20 mm in 120 s. B-mode and M-mode images displayed a
      hypoechoic region that agreed well with lesion depth observed by gross histology.
      These feasibility studies demonstrate that the dual-mode transducers had imaging
      performance that was sufficient to aid the guidance and monitoring of treatment,
      and could sustain high intensities to induce coagulation necrosis in vivo.

PMID- 19758674
TI  - Water temperature dependence of single bubble sonoluminescence threshold.
AB  - Water temperature dependence of single bubble sonoluminescence (SBSL) threshold
      has been experimentally measured to perform measurements at different
      temperatures on the very same bubble. Results show lower thresholds, i.e. an
      easier prime of mechanism, of sonoluminescence at lower water temperatures.
      Dependence is almost linear at lower temperatures while between 14 degrees C and
      about 20 degrees C the curve changes its slope reaching soon a virtual
      independence from water temperature above about 20 degrees C.

PMID- 19758675
TI  - Molecular characterization of human parvovirus B19 genotypes 2 and 3.
AB  - We have characterized the transcription profiles of parvovirus B19 (B19V)
      genotype-2 A6 and genotype-3 V9 variants. The A6 RNA profile differs from that of
      the prototype B19V in both B19V non-permissive and permissive cells, whereas the
      overall profile of the V9 RNA in these cells is similar to that of the prototype.
      A unique feature we have identified is that the genotype-2 A6 variant used only
      one splice acceptor to remove the first intron. We also demonstrated that the
      inverted terminal repeats (ITRs) of the prototype B19V support replication of the
      V9 genome, which produces infectious virus, but not that of the A6 genome, in
      B19V-permissive cells. Similar to the proapoptotic nature of the prototype B19V
      large non-structural protein (NS1), the A6 and V9 NS1 proteins also are potent
      inducers of apoptosis in B19V-permissive cells.

PMID- 19758676
TI  - Identification of recombinant human papillomavirus type 16 variants.
AB  - Intratypic diversity of human papillomavirus (HPV) genome is generally
      characterized by point mutation, insertion, and/or deletion. Using PCR-based
      cloning and sequencing, we detected concurrent infection with 8 HPV16 variants in
      a woman enrolled in the ASCUS-LSIL Triage Study. The European variant was the
      major variant; each of the 7 minor variants had partial DNA sequences identical
      to the European variant and another part identical to the African 2 variant. At a
      follow-up visit, only an HPV16 African 2 variant was detected. Results from the
      present study suggest presence of intratypic recombination of HPV genome in
      natural infection.

PMID- 19758677
TI  - A three-compartment model for micropollutants sorption in sludge: methodological
      approach and insights.
AB  - In sludge resulting from wastewater treatment, organic micropollutants sorb to
      particles and to dissolved/colloidal matter (DCM). Both interactions may
      influence their physical and biological fate throughout the wastewater treatment
      processes. To our knowledge, sludge has never been considered as a three
      compartment matrix, in which micropollutants coexist in three states: freely
      dissolved, sorbed-to-particles and sorbed-to-DCM. A methodology is proposed to
      concomitantly determine equilibrium constants of sorption to particles (K(part))
      and to DCM (K(DCM)). Polycyclic Aromatic Hydrocarbons (PAHs) were chosen as model
      compounds for the experiments. The logarithm of estimated equilibrium constants
      ranged from 3.1 to 4.3 and their usual correlation to PAH hydrophobicity was
      verified. Moreover, PAH affinities for particles and for DCM could be compared.
      Affinity for particles was found to be stronger, probably due to their physical
      and chemical characteristics. This work provided a useful tool to assess the
      freely dissolved, sorbed-to-particles and sorbed-to-DCM concentrations of
      contaminants, which are necessary to accurately predict their fate. Besides,
      guidelines to investigate the link between sorption and the fundamental concept
      of bioavailability were proposed.

PMID- 19758678
TI  - Toxicity assessment of sequential leachates of tire powder using a battery of
      toxicity tests and toxicity identification evaluations.
AB  - Approximately 460,000 ton of rubber are dispersed annually along the European
      roads due to tire wear. Tire rubber is known to leach compounds that are toxic to
      aquatic organisms. However, the potential effects of tire wear material on
      aquatic organisms at environmental relevant concentrations, and over time have so
      far not been extensively studied. In this study, rubber from three different
      tires was abraded and the powder leached in deionised water. The rubber powder
      was leached six times sequentially. All leachates were tested for toxicity using
      standardized toxicity tests including green algae (Pseudokirchneriella
      subcapitata, 72h growth inhibition), crustaceans (Daphnia magna, 24 and 48h
      immobility and Ceriodaphnia dubia, 48h survival and 9d reproduction and
      survival), and zebra fish eggs (Danio rerio, 48h lethality). The reproduction of
      C. dubia was the most sensitive endpoint tested, with an EC50 of 0.013 g L(-1) up
      to the third leaching of the most toxic tire, which is similar to a predicted
      concentration in road runoffs. The toxicity of all tires was reduced by the
      sequential leachings and after the sixth leaching the EC50s were >0.1 g L(-1) for
      all endpoints. Toxicity identification evaluations indicated that the toxicity
      was caused by zinc and organic compounds.

PMID- 19758679
TI  - Mixture toxicity assessment of cadmium and benzo[a]pyrene in the sea worm Hediste
      diversicolor.
AB  - In the present study, Hediste diversicolor biotransformation and anti-oxidant
      responses to acute exposure to cadmium (Cd) and to the polycyclic aromatic
      hydrocarbons benzo[a]pyrene (B[a]P) were investigated. Worms were submitted to
      0.2, 0.4 and 1 microM of each contaminant and to their mixture during a period of
      test of 48h. Following biological responses were measured: (1) NADPH cytochrome c
      reductase (NADPH cyt c) activity, as phase I biotransformation parameter; (2)
      gluthathione-S-transferase (GST) activity as a phase II conjugation enzyme, (3)
      catalase activity as anti-oxidant response and (4) malondialdehyde accumulation
      (MDA) as lipid peroxydation marker. The cholinergic system was evaluated using
      the acetylcholinesterase activity (AChE). Exposure to the mixture resulted in low
      dose level additive effects on the investigated biomarkers. However, worms
      exposed to 1 microM of the single compounds and to their mixture exhibited the
      highest MDA accumulation and the lowest enzymatic biomarkers activities
      suggesting severe toxicological effects. These data should be carefully
      considered in view of the biological effects of mixture pollutants and
      particularly in marine sediment ecosystems.

PMID- 19758680
TI  - The prehistory of handedness: archaeological data and comparative ethology.
AB  - Homo sapiens sapiens displays a species wide lateralised hand preference, with
      85% of individuals in all populations being right-handed for most manual actions.
      In contrast, no other great ape species shows such strong and consistent
      population level biases, indicating that extremes of both direction and strength
      of manual laterality (i.e., species-wide right-handedness) may have emerged after
      divergence from the last common ancestor. To reconstruct the hand use patterns of
      early hominins, laterality is assessed in prehistoric artefacts. Group right side
      biases are well established from the Neanderthals onward, while patchy evidence
      from older fossils and artefacts indicates a preponderance of right-handed
      individuals. Individual hand preferences and group level biases can occur in
      chimpanzees and other apes for skilled tool use and food processing. Comparing
      these findings with human ethological data on spontaneous hand use reveals that
      the great ape clade (including humans) probably has a common effect at the
      individual level, such that a person can vary from ambidextrous to completely
      lateralised depending on the action. However, there is currently no theoretical
      model to explain this result. The degree of task complexity and bimanual
      complementarity have been proposed as factors affecting lateralisation strength.
      When primatology meets palaeoanthropology, the evidence suggests species-level
      right-handedness may have emerged through the social transmission of increasingly
      complex, bimanually differentiated, tool using activities.

PMID- 19758681
TI  - Chemical composition of gases surgeons are exposed to during endoscopic
      urological resections.
AB  - OBJECTIVES: To identify any potentially harmful chemical constituents of the
      gaseous plume produced from urological endoscopic diathermy. METHODS: Chemical
      analysis was performed on the gaseous plume produced from prostatic resections
      and vaporizations using gas chromatography with mass spectroscopy and high
      performance liquid chromatography using ultraviolet and visible light detection.
      In addition, carbon monoxide levels were analyzed using a portable catalytic
      flammable gas sensor. RESULTS: This study identified a cocktail of volatile
      organic hydrocarbons produced during these procedures, some of which are known
      carcinogens. The most significant finding being high levels of carbon monoxide.
      CONCLUSIONS: From this preliminary study, we advocate the use of smoke evacuator
      systems for all urologists regularly performing these procedures, and suggest
      that further research is required to investigate potential long-term
      complications to the urologist.

PMID- 19758682
TI  - A 56-year-old man with a large nonfunctioning adrenal mass.

PMID- 19758683
TI  - Canary Prostate Active Surveillance Study: design of a multi-institutional active
      surveillance cohort and biorepository.
AB  - Active surveillance is a management plan for localized prostate cancer that
      offers selective delayed intervention on indication of disease progression,
      allowing patients to delay or avoid treatment and associated side-effects.
      Outcomes from centers that promote active surveillance are favorable, with high
      rates of disease-specific survival. However, there remains a need for prognostic
      variables or biomarkers that distinguish with high specificity the aggressive
      cancers that progress on surveillance from the indolent cancers. The Canary
      Prostate Active Surveillance Study is a multicenter study and a biorepository
      that will discover and confirm biomarkers of aggressive disease as defined by
      histologic, prostate-specific antigen, or clinical criteria.

PMID- 19758684
TI  - Pathological upstaging during radical cystectomy is associated with worse
      recurrence-free survival in patients with bacillus Calmette-Guerin-refractory
      bladder cancer.
AB  - OBJECTIVES: To compare the outcomes of patients who were upstaged to pT2 at the
      time of radical cystectomy (RC) to those who were correctly staged as T2 before
      RC. METHODS: The clinical and pathologic data were reviewed of 496 patients who
      underwent RC from 1994 to 2008. Patients who underwent RC for high-grade T1
      (HGT1) or carcinoma in situ (CIS) (184) were compared with those with known
      muscle-invasive cancer (312) before RC. Patients were substratified based on
      preoperative intravesical therapy status. Recurrence-free survival (RFS) for
      patients who were upstaged to muscle-invasive disease was compared with patients
      who were correctly staged T2 preoperatively. RESULTS: Patients who were upstaged
      to pT2 disease had significantly worse 3- and 5-year RFS compared with those who
      where accurately staged (cT2 = pT2) (64% and 61% vs 83% and 74%, respectively; P
      = .04). Upstaging to pT2 in patients with a history of bacillus Calmette-Guerin
      treatment resulted in worse 3- and 5-year RFS rates compared with those
      accurately staged (69% and 57% vs 100% and 86%, respectively; P = .03).
      CONCLUSIONS: Upstaging to pT2 among patients with HGT1 or CIS is associated with
      worse RFS compared with patients with known muscle invasion before RC (HGT1/CIS =
      pT2 vs cT2 = pT2). This finding was most significant among patients with a
      history of bacillus Calmette-Guerin treatment. Factors such as understaging of
      disease or treatment delay may contribute to worse outcomes among this subset of
      patients and should be considered when discussing treatment options.

PMID- 19758685
TI  - Pure natural orifice translumenal endoscopic surgery partial cystectomy:
      intravesical transurethral and extravesical transgastric techniques in a porcine
      model.
AB  - OBJECTIVES: To describe 2 pure natural orifice translumenal endoscopic surgery
      (NOTES) techniques for partial cystectomy in a porcine model. NOTES is a new
      minimally invasive modality for performing abdominal surgery without
      transcutaneous incision. METHODS: Transurethral-A rigid cystoscope is inserted
      into the porcine bladder with CO(2) insufflation. With an endoscopic loop device
      and a grasping device, the targeted area of the bladder is manipulated into the
      loop. The bladder segment is excised with electrocautery. Transgastric-A
      gastrotomy is made with a dual channel endoscope in the porcine stomach. The
      endoscope is inserted and pneumoperitoneum is established by insufflation through
      a channel. After identifying bladder, 2 endoscopic loops are placed at the
      intended area of resection. An incision is made between the loops to excise the
      specimen. In both cases, full-thickness specimen is removed en bloc with the
      scope and the defect is reapproximated with endoscopic clips. RESULTS:
      Transurethral and transgastric NOTES approaches were achieved using standard
      endoscopic equipment in a porcine model. Transurethral NOTES partial cystectomy
      was successful in acute (n = 2) and chronic (n = 2) models. The transgastric
      NOTES approach was successfully performed in an acute animal. CONCLUSIONS: NOTES
      partial cystectomy could potentially reduce morbidity of conventional methods of
      partial cystectomy. Transurethral NOTES may be the least invasive method possible
      for partial cystectomy. Potential advantages of a transgastric NOTES approach
      include visualization of adjacent structures, access to sites difficult to reach
      transurethrally, and lymph node sampling. However, a gastrotomy could be a source
      of morbidity. Further investigation is required to assess safety, efficacy, and
      adequate bladder healing.

PMID- 19758686
TI  - Cryoimmunotherapy in urologic oncology.
AB  - Cryoablation is gaining acceptance as a primary treatment of localized as well as
      a salvage therapy of metastatic urologic malignancies. Anecdotal clinical reports
      suggest cryoablation can induce a systemic anti-tumor immune response; this
      phenomenon has been confirmed in animal models. To capitalize on this stimulatory
      effect of cryotherapy for control of advanced malignancies, it must be further
      intensified. This article reviews the existing evidence regarding cryoimmunology
      and discusses the mechanisms for generation of an anti-tumor immune response.
      Several immunotherapy approaches that can be combined with cryoablation to devise
      a cryoimmunotherapeutic strategy with potential to affect the progression of
      metastatic disease are described.

PMID- 19758687
TI  - Health information quality on the internet in urological oncology: a multilingual
      longitudinal evaluation.
AB  - OBJECTIVES: To compare the quality of uro-oncological Web sites, to assess for
      language or disease differences across Western languages, and to perform a
      longitudinal comparison between 2004 and 2009. Uro-oncological Internet
      information quality is considered variable but no comprehensive analysis exists.
      METHODS: Health on the Net (HON) principles may be applied to Web sites using an
      automated toolbar function. Using the Google search engine
      (http://www.Google.com), in 2004 and 2009, 2400 Web sites were assessed using the
      keywords prostate, bladder, kidney, and testicular cancer in English, French,
      German, and Spanish. The first 150 Web sites in each language had HON principles
      measured-a comparison between 2004 and 2009 was done. A further analysis of site
      sponsorship was undertaken. RESULTS: Regardless of language or cancer type, most
      sites are not HON accredited. English has consistently more than English, French,
      Spanish, or German. For the respective languages in 2009, prostate has the most
      (29, 14%, 16%, 12%), followed by bladder (29%, 22%, 14%, 13%), kidney (25%, 15%,
      10%, 13%), and testis (26%, 19%, 7.11%). Significant differences were found
      comparing language and organ groups. The quality improved from 2004 to 2009.
      Nonprofit organizations (51%), government and/or educational (39%), commercial
      (20%), with urologists last (14%) were accredited. CONCLUSIONS: A lack of
      validation of most uro-oncological sites should be appreciated by urologists.
      Additionally, there is a discrepancy in quality and number of Web sites across
      uro-oncological diseases and major Western European languages, but with some
      improvement seen recently. We need to encourage informative, ethical, and
      reliable complimentary health Web sites on the Internet and direct patients to
      them.

PMID- 19758688
TI  - Prognostic factors for chronic kidney disease after curative surgery in patients
      with small renal tumors.
AB  - OBJECTIVES: To investigate the incidence and predictive factors associated with
      newly developed chronic kidney disease (CKD) after curative surgery in patients
      with small renal tumors. METHODS: From 1998 to 2005, we retrospectively
      investigated 225 patients undergoing partial nephrectomy (PN) or radical
      nephrectomy (RN) for renal tumors, of size <or= 4 cm, with normal contralateral
      kidney. The glomerular filtration rate (GFR) was calculated using the four
      variable modification of diet in renal disease formula. CKD was defined as GFR of
      < 60 mL/min per 1.73 m(2). Demographic and clinicopathologic parameters were
      evaluated using Cox proportional hazards model to determine the variables
      independently associated with the development of postoperative CKD. RESULTS: A
      total of 129 (57.3%) and 96 (42.7%) patients were included in the RN and PN
      groups. A total of 97 patients (43.1%) developed CKD; 86 (66.7%) underwent an RN
      and 11 (11.5%) underwent a PN. The 2-year probability of absence of CKD with an
      RN and a PN was 58.3% and 95.7%, respectively (P <.001). Among 20 patients with
      diabetes, 12 (60.0%) developed CKD: 10 patients underwent an RN and 2, a PN. The
      2-year probability of absence of CKD with and without diabetes was 46.5% and
      76.4%, respectively (P = .006). The multivariate analysis showed that age (P =
      .001), type of operation (P <.001), preoperative GFR (P = .001), and diabetes (P
      = .042) were associated with the development of CKD. CONCLUSIONS: The results of
      this study show that nephron-sparing surgery for small renal mass should be
      attempted to prevent CKD in all eligible patients, especially those with
      diabetes.

PMID- 19758689
TI  - Cardiac history and risk of post-cystectomy cardiac complications.
AB  - OBJECTIVES: To evaluate risk factors for postoperative cardiac complications
      (POCC). Patients undergoing cystectomy often have significant baseline cardiac
      disease. Despite preoperative medical optimization, postoperative cardiac
      complications remain a significant source of morbidity. METHODS: A retrospective
      review of all radical cystectomies for bladder cancer between January 2004 and
      September 2006 was performed. Twelve preoperative risk factors were evaluated,
      including age, Charlson Comorbidity Index, type of urinary diversion, and
      previous cardiac history. All complications, including myocardial infarction (MI)
      and new onset arrhythmia, were recorded for 90 days postoperatively. Univariate
      and multivariate analysis were performed. RESULTS: A total of 283 patients
      underwent cystectomy for bladder cancer between January/2004 and September 2006.
      The median age of the cohort was 70 (35-90) years. Of 283 patients, 64 (23%) had
      a significant preoperative cardiac history, including 18 (6%) with prior coronary
      artery bypass and 30 (11%) with a history of MIs. Thirty-one (11%) patients had
      either new onset arrhythmia (22, 8%) or MI (10, 4%) and 1 had both. On univariate
      analysis, cardiac history, age, type of urinary diversion, and the Charlson
      Comorbidity Index demonstrated significance. The risk of POCC was associated with
      ileal conduit urinary diversion (P = .026, OR 5.58 [1.23-25.36]) and the Charlson
      Index score (P = .030, OR 1.28 [1.024-1.60]) on multivariate analysis.
      CONCLUSIONS: Multiple, inter-related factors may predict cardiac complications in
      the early postoperative period. Despite perioperative optimization, patients with
      a prior cardiac history should be counseled, regarding the increased risk of
      postoperative cardiac complications. The association between cardiac
      complications and ileal conduit diversion highlights the selection bias toward
      patients with preexisting comorbid disease.

PMID- 19758690
TI  - Clinical audit in gynecological cancer surgery: development of a risk scoring
      system to predict adverse events.
AB  - BACKGROUND: Advanced gynecological surgery undertaken in a specialized
      gynecologic oncology unit may be associated with significant perioperative
      morbidity. Validated risk prediction models are available for general surgical
      specialties but currently not for gynecological cancer surgery. OBJECTIVE: The
      objective of this study was to evaluate risk factors for adverse events (AEs) of
      patients treated for suspected or proven gynecological cancer and to develop a
      clinical risk score (RS) to predict such AEs. METHODS: AEs were prospectively
      recorded and matched with demographical, clinical and histopathological data on
      369 patients who had an abdominal or laparoscopic procedure for proven or
      suspected gynecological cancer at a tertiary gynecological cancer center.
      Stepwise multiple logistic regression was used to determine the best predictors
      of AEs. For the risk score (RS), the coefficients from the model were scaled
      using a factor of 2 and rounded to the nearest integer to derive the risk points.
      Sum of all the risk points form the RS. RESULTS: Ninety-five patients (25.8%) had
      at least one AE. Twenty-nine (7.9%) and 77 (20.9%) patients experienced intra-
      and postoperative AEs respectively with 11 patients (3.0%) experiencing both. The
      independent predictors for any AE were complexity of the surgical procedure,
      elevated SGOT (serum glutamic oxaloacetic transaminase, > or /=35 U/L), higher
      ASA scores and overweight. The risk score can vary from 0 to 14. The risk for
      developing any AE is described by the formula 100 / (1 + e((3.697 - (RS /2)))).
      CONCLUSION: RS allows for quantification of the risk for AEs. Risk factors are
      generally not modifiable with the possible exception of obesity.

PMID- 19758691
TI  - A review of the challenges faced in the conservative treatment of young women
      with endometrial carcinoma and risk of ovarian cancer.
AB  - OBJECTIVE: The standard management for women diagnosed with endometrial carcinoma
      (EC) is hysterectomy with salpingo-oophorectomy. However, more conservative
      treatment approaches, including uterine and ovarian preservation, may be used for
      women who have a strong desire to maintain fertility in spite of potential
      oncologic risks. METHODS: We reviewed the literature regarding fertility
      preserving treatment for EC. We also conducted medical chart reviews for two
      young patients diagnosed with EC whose treatment deviated from the standard
      approach in order to preserve fertility. These patients were subsequently
      diagnosed with ovarian cancer. Our review summarizes the literature regarding the
      clinical and emotional implications of fertility preservation in young women.
      CASES: Two young nulliparous women (29 and 23 years, respectively) with grade 1
      endometrioid adenocarcinoma were initially treated with conservative fertility
      sparing endocrine therapy. Upon failure of endocrine treatment both women
      underwent hysterectomy and staging with ovarian preservation. During
      surveillance, both women were subsequently diagnosed with ovarian carcinoma and
      underwent bilateral salpingo-oophorectomy (BSO) and comprehensive staging.
      CONCLUSION: The management of young women with endometrial cancer can be complex
      and challenging. Patients and physicians are confronted with the dilemma of
      following standard surgical guidelines versus the desire to maintain fertility
      and avoid surgical menopause. Careful oncologic, psychotherapeutic, genetic and
      reproductive counseling is advised before offering a non-standard treatment
      strategy to young endometrial cancer patients.

PMID- 19758693
TI  - Clinically important head injuries after head trauma in children.

PMID- 19758694
TI  - The presence of both bone sialoprotein-binding protein gene and collagen adhesin
      gene as a typical virulence trait of the major epidemic cluster in isolates from
      orthopedic implant infections.
AB  - Staphylococcus aureus is a major, highly clonal, pathogen causing implant
      infections. This study aimed at investigating the diverse distribution of
      bacterial adhesins in most prevalent S. aureus strain types causing orthopaedic
      implant infections. 200 S. aureus isolates, categorized into ribogroups by
      automated ribotyping, i.e. rDNA restriction fragment length polymorphism
      analysis, were screened for the presence of a panel of adhesins genes. Within the
      collection of isolates, automated ribotyping detected 98 distinct ribogroups. For
      many ribogroups, characteristic tandem genes arrangements could be identified. In
      the predominant S. aureus cluster, enlisting 27 isolates, the bbp gene encoding
      bone sialoprotein-binding protein appeared a typical virulence trait, found in
      93% of the isolates. Conversely, the bbp gene was identified in just 10% of the
      remaining isolates of the collection. In this cluster, co-presence of bbp with
      the cna gene encoding collagen adhesin was a pattern consistently observed. These
      findings indicate a crucial role of both these adhesins, able to bind the most
      abundant bone proteins, in the pathogenesis of orthopaedic implant infections,
      there where biomaterials interface bone tissues. This study suggests that
      specific adhesins may synergistically act in the onset of implant infections and
      that anti-adhesin strategies should be targeted to adhesins conjointly present.

PMID- 19758692
TI  - Identification of children at very low risk of clinically-important brain
      injuries after head trauma: a prospective cohort study.
AB  - BACKGROUND: CT imaging of head-injured children has risks of radiation-induced
      malignancy. Our aim was to identify children at very low risk of clinically
      important traumatic brain injuries (ciTBI) for whom CT might be unnecessary.
      METHODS: We enrolled patients younger than 18 years presenting within 24 h of
      head trauma with Glasgow Coma Scale scores of 14-15 in 25 North American
      emergency departments. We derived and validated age-specific prediction rules for
      ciTBI (death from traumatic brain injury, neurosurgery, intubation >24 h, or
      hospital admission >or=2 nights). FINDINGS: We enrolled and analysed 42 412
      children (derivation and validation populations: 8502 and 2216 younger than 2
      years, and 25 283 and 6411 aged 2 years and older). We obtained CT scans on 14
      969 (35.3%); ciTBIs occurred in 376 (0.9%), and 60 (0.1%) underwent neurosurgery.
      In the validation population, the prediction rule for children younger than 2
      years (normal mental status, no scalp haematoma except frontal, no loss of
      consciousness or loss of consciousness for less than 5 s, non-severe injury
      mechanism, no palpable skull fracture, and acting normally according to the
      parents) had a negative predictive value for ciTBI of 1176/1176 (100.0%, 95% CI
      99.7-100 0) and sensitivity of 25/25 (100%, 86.3-100.0). 167 (24.1%) of 694 CT
      imaged patients younger than 2 years were in this low-risk group. The prediction
      rule for children aged 2 years and older (normal mental status, no loss of
      consciousness, no vomiting, non-severe injury mechanism, no signs of basilar
      skull fracture, and no severe headache) had a negative predictive value of
      3798/3800 (99.95%, 99.81-99.99) and sensitivity of 61/63 (96.8%, 89.0-99.6). 446
      (20.1%) of 2223 CT-imaged patients aged 2 years and older were in this low-risk
      group. Neither rule missed neurosurgery in validation populations.
      INTERPRETATION: These validated prediction rules identified children at very low
      risk of ciTBIs for whom CT can routinely be obviated. FUNDING: The Emergency
      Medical Services for Children Programme of the Maternal and Child Health Bureau,
      and the Maternal and Child Health Bureau Research Programme, Health Resources and
      Services Administration, US Department of Health and Human Services.

PMID- 19758695
TI  - Calcineurin activation by slow calcium release from intracellular stores
      suppresses protein kinase C regulation of L-type calcium channels in L6 cells.
AB  - L-type Ca(2+) channel activity was assayed in L6 cells as the rate of nifedipine
      sensitive Ba(2+) influx in a depolarizing medium. In the absence of extracellular
      Ca(2+), activation of protein kinase C (PKC) with phorbol-12-myristate-13-acetate
      (PMA) or thymeleatoxin (TMX) inhibited Ba(2+) influx by 38%. Thapsigargin (Tg), a
      selective inhibitor of the Ca(2+)-ATPase in the sarcoplasmic reticulum, evoked a
      rise in the cytosolic Ca(2+) concentration ([Ca(2+)](i)) in a Ca(2+)-free medium
      from 30 to approximately 80 nM. This [Ca(2+)](i) increase declined slowly, giving
      rise to a modest elevation of [Ca(2+)](i) that persisted for >5 min. The
      inhibitory effects of PMA and TMX on channel activity were abolished when tested
      in Tg-treated cells in a Ca(2+)-free medium. However, when the Ca(2+) ionophore,
      ionomycin, was applied with Tg, PMA and TMX retained their inhibitory effect on L
      type Ca(2+) channel activity, suggesting that a lower amplitude and prolonged
      release of Ca(2+) stores is necessary for abrogating PKC-mediated inhibition of
      LCC. Cyclosporin A (5 microM) and ascomycin (5 microM), inhibitors of the
      Ca(2+)/calmodulin-dependent protein phosphatase, calcineurin, fully restored the
      inhibitory effect of PMA and TMX on channel activity. Addition of 1mM CaCl(2) to
      the Tg-treated cells increased [Ca(2+)](i) to approximately 165 nM and also
      restored the inhibitory effects of PMA and TMX. These results indicate that a
      small, relatively prolonged [Ca(2+)](i) increase elicited by passive depletion of
      internal Ca(2+) stores led to activation of calcineurin, giving rise to an
      increase in protein phosphatase activity that counteracted the inhibitory effects
      of PKC on channel activity. A larger increase in [Ca(2+)](i) via store-dependent
      Ca(2+) entry enhanced the activity of PKC sufficiently to overcome the protein
      phosphatase activity of calcineurin. This study is the first to demonstrate that
      the regulation of L-type Ca(2+) channels in a myocyte model involves a balance
      between the differential Ca(2+) sensitivities and opposing actions of PKC and
      calcineurin.

PMID- 19758696
TI  - FISH and SNP-A karyotyping in myelodysplastic syndromes: improving cytogenetic
      detection of del(5q), monosomy 7, del(7q), trisomy 8 and del(20q).
AB  - Cytogenetic aberrations identified by metaphase cytogenetics (MC) have important
      diagnostic, prognostic and therapeutic roles in myelodysplastic syndromes (MDS).
      Fluorescence in situ hybridization (FISH) complements MC by the ability to
      evaluate large numbers of both interphase and metaphase nuclei. However,
      clinically practical FISH strategies are limited to detection of known lesions.
      Single nucleotide polymorphism array (SNP-A)-based karyotyping can reveal
      unbalanced defects with superior resolution over MC and FISH and identify
      segmental uniparental disomy (UPD) undetectable by either method. Using a
      standardized approach, we focused our investigation on detection of -5/del(5q), 
      7/del(7q), trisomy 8 and del(20q) in patients with MDS (N=52),
      MDS/myeloproliferative overlap syndromes (N=7) and acute myeloid leukemia (N=15)
      using MC, FISH and SNP-A karyotyping. The detection rate for del(5q) was 30, 32
      and 32% by MC, FISH, and SNP-A, respectively. No single method detected all
      defects, and detection rates improved when all methods were used. The rate for
      detection of del(5q) increased incrementally to 35% (MC+FISH), 38% (MC+SNP-A),
      38% (FISH+SNP-A) and 39% (all three methods). Similar findings were observed for 
      7/del(7q), trisomy 8 and -20/del(20q). We conclude that MC, FISH and SNP-A are
      complementary techniques that, when applied and interpreted together, can improve
      the diagnostic yield for identifying genetic lesions in MDS and contribute to the
      better description of abnormal karyotypes.

PMID- 19758697
TI  - Polymorphisms in glucocorticoid receptor gene and the outcome of childhood acute
      lymphoblastic leukemia (ALL).
AB  - Childhood acute lymphoblastic leukemia patients (n=310) were analyzed for four
      SNPs in the NR3C1 gene. Polymorphisms -627A/G, intron 2 +646C/G and 9bT/C were
      all associated with reduced event-free survival. Haplotypes composed of AGT
      alleles at these loci and tagged by the intron 2 +646G variant also associated
      with lower event-free survival (p=0.03). The progressive impact of this haplotype
      on outcome was seen with two copies associated with reduced overall survival
      (p=0.05). Quantitative mRNA analysis in lymphoblastoid cell lines showed that
      carriers of the AGT haplotype had a higher ratio of GR gamma/alpha isoforms
      (p=0.04), which possibly explains its association with reduced event-free
      survival and overall survival.

PMID- 19758698
TI  - Therapeutic implications of Src independent calcium mobilization in diffuse large
      B-cell lymphoma.
AB  - We report that 38% of primary large B-cell lymphoma (DLBCL) tested expressed
      active Src family kinases, which are targeted by dasatinib. The expression of
      active Src family of kinases (SFK) in primary DLBCL tumors correlated with
      unfavorable prognostic markers such as Ki67 and Mum1. Using four DLBCL cell lines
      we found that: (1) sensitivity to dasatinib (but not imatinib) varied 400-fold;
      (2) dasatinib resistance was associated with distinct signaling profiles
      downstream of BCR activation. In particular, although Src family kinase
      phosphorylation was inhibited by 100-150 nM dasatinib in all cell lines, this
      failed to inhibit BCR-mediated Blnk phosphorylation, calcium signaling and
      proliferation in a dasatinib resistant cell line.

PMID- 19758699
TI  - A validation study of the Dutch Childhood Trauma Questionnaire-Short Form: factor
      structure, reliability, and known-groups validity.

PMID- 19758700
TI  - Cultural protective and risk factors: professional perspectives about child
      sexual abuse in Kenya.
AB  - OBJECTIVE: The aim of this study was to explore perspectives on cultural risks
      and protective factors among professionals in Kenya. METHOD: An
      exploratory/descriptive survey of Kenyan professionals working to prevent or
      intervene with child sexual abuse was undertaken to determine their perspectives
      on how tribal culture impacts vulnerability to sexual abuse. Participants at a
      conference workshop, were grouped according to tribal affiliation and asked to
      list key factors that they believe increase or decrease risk to children of
      sexual abuse in that tribe. Participants from seven ethnic groupings (Somali,
      Miji Kendas, Luo, Kamba, Kikuyu, Kalenjin, Kisii) identified factors which were
      then categorized by themes using qualitative examination. RESULTS: Participants
      identified a number of cultural factors that protect children from sexual abuse
      as well as those that create risk for sexual abuse. Strong similarities were
      identified across groups; however in some cases factors viewed as risks by some
      were viewed as protective by others. CONCLUSIONS: In this exploratory study in
      Kenya, professionals identified many culturally supported practices that protect
      against or create potential risks for child sexual abuse. Awareness of traditions
      and practices may inform creation of interventions for preventing child sexual
      abuse. PRACTICE IMPLICATIONS: Cultural/community level factors must be considered
      in designing prevention and intervention programs, particularly in more
      collective societies.

PMID- 19758701
TI  - Development and psychometric evaluation of a new assessment method for childhood
      maltreatment experiences: the interview for traumatic events in childhood (ITEC).
AB  - OBJECTIVE: We conducted a comprehensive assessment of the reliability and
      validity of the Interview for Traumatic Events in Childhood (ITEC, Lobbestael,
      Arntz, Kremers, & Sieswerda, 2006), a retrospective, semi-structured interview
      for childhood maltreatment. The ITEC aims to yield dimensional scores for
      severity of experiences of different childhood maltreatment dimensions. METHODS:
      Initial psychometric properties were tested with the pilot version of the ITEC in
      362 participants. A second study assessed the revised ITEC in 217 participants,
      patients and non-patients. RESULTS: Factor analyses produced the best fit for a
      five-factor model (sexual, physical and emotional abuse, physical and emotional
      neglect). The scales had good internal consistency, except for the physical
      neglect subscale, and excellent inter-rater reliability. The scales were highly
      associated with equivalent scales of the Childhood Trauma Questionnaire (i.e.,
      good convergent validity), and showed good correspondence with patient file
      information (i.e., good criterion validity). CONCLUSION: These results support
      the reliability and validity of the ITEC, making it a potentially useful tool for
      assessing a broad range of traumatic events in childhood. PRACTICE IMPLICATION:
      The first step in therapy for dealing with childhood maltreatment is to map
      abusive experiences and assess their severity and impact. Since maltreatment is a
      sensitive topic that is not reported on easily, trauma interviews are promising
      assessment instruments since they provide the opportunity to probe and clarify.
      There are hardly any well-validated trauma interviews available that assess the
      extent of maltreatment in and outside the family in various dimensions. The
      current study tries to fill this gap by presenting a new trauma interview; the
      Interview for Traumatic Events in Childhood.

PMID- 19758702
TI  - Youth at work: adolescent employment and sexual harassment.
AB  - OBJECTIVE: An examination of the frequency and impact of workplace sexual
      harassment on work, health, and school outcomes on high school girls is presented
      in two parts. The first compares the frequency of harassment in this sample (52%)
      to published research on adult women that used the same measure of sexual
      harassment. The second part compares outcomes for girls who experienced
      harassment versus those who did not. METHODS: Students in a small, suburban high
      school for girls completed a paper and pencil survey during class. A modified
      version of the Sexual Experiences Questionnaire (SEQ: Fitzgerald et al., 1988)
      was used to identify sexually harassed working teenagers. Work attitudes,
      assessments of physical health and mental health, and school-related outcomes
      were measured using standardized scales. Data were analyzed using difference of
      proportions tests, t-tests, and regression. RESULTS: The percentage of harassed
      girls was significantly higher than the figures reported in most studies of
      working women. Girls who were sexually harassed were less satisfied with their
      jobs and supervisors, had higher levels of academic withdrawal, and were more apt
      to miss school than their non-harassed peers. CONCLUSIONS: Sexual harassment
      significantly impacts employed high school girls' connections to work and school.
      It not only taints their attitudes toward work but it also threatens to undermine
      their commitment to school. Educators, practitioners and community leaders should
      be aware of the negative impact this work experience may have on adolescents and
      explore these issues carefully with students who are employed outside of school.
      PRACTICE IMPLICATIONS: Teenage students, stressed by sexual harassment
      experienced at work may find their career development or career potential impeded
      or threatened due to school absence and poor academic performance. In addition,
      the physical safety of working students may be at risk, creating a need for
      teenagers to receive training to deal with sexual assault and other types of
      workplace violence. Educators, practitioners, and community leaders should be
      aware of the negative impact this work experience may have on adolescents and
      their overall school experience and explore the issue of sexual harassment
      carefully with students who are employed outside of school.

PMID- 19758703
TI  - Condition and pyloric caeca as indicators of food web effects in fish living in
      metal-contaminated lakes.
AB  - Variations in fish condition, pyloric caeca (PC) mass and tissue metal
      concentrations were examined in two consecutive summers in yellow perch collected
      along two polymetallic gradients in Canada, Sudbury (ON) and Rouyn-Noranda (QC).
      The potential of PC mass variations to help interpret food web-mediated changes
      in condition was also evaluated. The lack of relationships between PC weight and
      condition, even in reference lakes, indicated that factors other than feeding
      rate influenced fish condition. Inter-annual variations in fish condition (12
      58%), PC weight (14-20%) and tissue metal concentrations (30-550%) were often of
      greater magnitude than differences between reference and contaminated fish
      sampled in the same year. The apparent lack of correspondence between feeding
      rate and condition and the large inter-annual variation in examined metrics
      highlight the need to better understand the ecological underpinnings that
      influence metal toxicity in field situations.

PMID- 19758704
TI  - Personality predicts recurrence of late-life depression.
AB  - OBJECTIVE: To examine the association of personality with recurrence of
      depression in later life. METHOD: A subsample of 91 subjects from the
      Longitudinal Aging Study Amsterdam (LASA; baseline sample size n=3107; aged > or
      = 55 years) depressed at baseline, who had recovered in the course of three years
      (first follow-up cycle) was identified. 41 (45%) respondents experienced a
      recurrence during the subsequent six years. The influences of personality and
      late life stress (demographic factors, health and social factors) on recurrence
      were investigated prospectively. RESULTS: Recurrence of depression was associated
      with a high level of neuroticism and low level of mastery, residual depressive
      symptoms at time of recovery, female gender, pain complaints and feelings of
      loneliness. In multivariable analysis entering all predictors significant in
      single variable analysis, residual depressive symptoms and lack of mastery
      remained significantly associated with recurrence. CONCLUSION: In predicting the
      recurrence of depression in later life, the direct effects of personality remain
      important and comparable in strength with other late life stressors related to
      recurrence.

PMID- 19758705
TI  - Comparative study of neurocognitive function in euthymic bipolar patients and
      stabilized schizophrenic patients.
AB  - Few studies have compared neurocognitive performance in euthymic patients with
      bipolar disorder (BD), stabilized patients with schizophrenia (SC) and normal
      controls (NC) using a comprehensive neuropsychological battery, and those that
      have been conducted have yielded discrepant results. We evaluated the
      neurocognitive profile shown by 73 euthymic patients with BD, 89 stabilized
      patients with SC and 67 NC. All participants completed a cognitive battery in
      which the domains evaluated were executive functioning, sustained attention, and
      verbal and visual memory. Individuals with BD were administered the Quality of
      Life Scale (QLS). Patients with BD manifested dysfunction in executive
      functioning (moderate-to-large effect size), sustained attention (moderate effect
      size) and verbal/visual memory (large effect size) compared with NC. Verbal
      memory deficit in patients with BD was related to poor functional outcome on the
      QLS and Global Assessment of Functioning (GAF). Patients with BD performed
      significantly better than patients with SC on the Trail Making Test (TMT) part B,
      backward digit span, and California Verbal Learning Test (CVLT) learning trials.
      Other neuropsychological measures showed no significant differences between the
      two patient groups. These findings support the notion that euthymic BD patients
      suffer from an extensive neurocognitive deficit that affects all cognitive
      domains and is qualitatively similar to that in SC patients. Persistent verbal
      memory impairment in BD has clinical relevance because it is associated with poor
      psychosocial function.

PMID- 19758706
TI  - Are self-injurers impulsive?: Results from two behavioral laboratory studies.
AB  - Common clinical wisdom suggests that people who engage in self-injury are
      impulsive. However, virtually all prior work in this area has relied on
      individuals' self-report of impulsiveness, despite evidence that people are
      limited in their ability to accurately report on cognitive processes that occur
      outside awareness. To address this knowledge gap, we used performance-based
      measures of several dimensions of impulsiveness to assess whether people engaging
      in non-suicidal self-injury (NSSI) demonstrate greater impulsiveness than non
      injurers. In Study 1, we compared adolescent self-injurers (n=64) to age-, sex-,
      and race/ethnicity-matched, non-injurious controls (n=30) on self-reported
      impulsiveness (Schedule for Affective Disorders and Schizophrenia for School Age
      Children, Present and LifetimeVersion) and on performance-based measures of two
      dimensions of impulsiveness: behavioral disinhibition (Conners' Continuous
      Performance Test) and risky decision-making (Iowa Gambling Task). In Study 2, we
      compared adult female self-injurers (n=20) with age- and race/ethnicity-matched,
      non-injurious controls (n=20) on self-reported impulsiveness (Barratt
      Impulsiveness Scale-11), and performance-based measures of behavioral
      disinhibition, risky decision-making, and two measures of delay discounting. In
      both studies, self-injurers reported greater impulsiveness; however, performance
      based measures of impulsiveness failed to detect any between-group differences.
      We propose several potential explanations for the discrepancies observed between
      self-report and performance-based measures of impulsiveness and discuss
      directions for future research on impulsiveness and self-injury.

PMID- 19758707
TI  - Interferon-beta-1a treatment increases CD56bright natural killer cells and
      CD4+CD25+ Foxp3 expression in subjects with multiple sclerosis.
AB  - Disease modifying effects of interferon (IFN)-beta therapy in patients with
      multiple sclerosis (MS) may be mediated in part through enhanced immunoregulation
      by the CD56(bright) subpopulation of natural killer (NK) cells and by Foxp3+ (not
      italicized) CD4+CD25+ regulatory T cells (Treg). We found that IFN-beta-1a(IM)
      treatment of relapsing-remitting (RR)MS subjects over 12 months significantly
      increased both percentage of CD56(bright) NK cells and Foxp3 mRNA expression
      compared to baseline values, untreated RRMS subjects and healthy controls (HC).
      This striking enhancement of two prominent immunoregulatory pathways lends
      support to the idea that beneficial effects of IFN-beta-1a in MS include control
      of pernicious autoimmunity.

PMID- 19758708
TI  - A child with lipoid proteinosis of larynx, skin and lymph nodes.

PMID- 19758709
TI  - Endoscopic surgery for the treatment of pediatric subperiosteal orbital abscess:
      a report of 10 cases.
AB  - INTRODUCTION: The pediatric subperiosteal abscess is considered an infectious
      process characterized by an abscess pocket localized between the lamina papiracea
      and the periorbita. Usually the surgical management is used to drain the
      collection of pus. METHODS: Between January 2006 and January 2009, 10 patients of
      age under 18-year-old underwent through a transnasal endoscopic approach at the
      University of Bologna, Sant'Orsola Malpighi Hospital for the treatment of a
      subperiosteal orbital abscess. All these patients were taken to the operative
      room in order to drain the abscess only after that the CT scan was accomplished
      and it demonstrated the presence of a subperiosteal orbital abscess. RESULTS: The
      transnasal endoscopic approach was used alone in 9 cases while it was associated
      with an external approach in one case for the treatment of a superolateral based
      subperiosteal orbital abscess. In all cases the exudate was obtained during the
      surgical procedure for the microbiological examination, although only 2 out of 10
      cases had positive abscess cultures for Streptococcus pneumoniae. CONCLUSIONS:
      The transnasal endoscopic approach is an effective surgical treatment to drain
      the collection of pus in all medially based subperiosteal orbital abscess, while
      it can be associated with an external approach for the treatment of a
      superolateral based subperiosteal orbital abscess.

PMID- 19758710
TI  - Effectiveness of transnasal endoscopic powered adenoidectomy in patients with
      choanal adenoids.
AB  - OBJECTIVES: To demonstrate the technique and efficacy of powered assisted
      adenoidectomy using nasal endoscopy. PATIENTS AND METHODS: Between 2002 and 2003,
      forty children (age ranged from 3 to 17 years) with symptoms and signs suggestive
      of snoring and/or obstructive sleep apnea and choanal adenoids were randomly
      selected and distributed in two groups. Group A underwent transnasal endoscopic
      powered adenoidectomy (TEPA) and group B underwent curettage adenoidectomy (CA).
      Both groups underwent pre- and postoperative nasal endoscopy. Direct comparisons
      between the two groups were made with regards to operative time, amount of blood
      loss, postoperative morbidity, complications, and resolution of symptoms.
      RESULTS: Male to female distribution was equal 1:1. The mean age of both groups
      was 8 years. In group A, the mean blood loss was 8.2 ml compared to 22.1 ml in
      group B (p<0.05). The operative time in group A was 6.1 min vs 12.3 min in group
      B (p<0.05). There were no operative or postoperative complications in both
      groups. Postoperative follow up and nasal endoscopy showed no recurrence of
      symptoms or adenoid remnants. CONCLUSION: Using TEPA for removing choanal
      adenoids is an adequate and safe method. The TEPA technique can be added to the
      armamentarium of techniques used by pediatric otolaryngologists.

PMID- 19758711
TI  - Mastoiditis in a paediatric population: a review of 11 years experience in
      management.
AB  - OBJECTIVE: This study explores the experience at Sydney Children's Hospital (SCH)
      managing children with acute mastoiditis and establishes a robust treatment
      algorithm. METHODS: Retrospective review of all patients admitted to SCH with an
      ICD-10 coding of "Mastoiditis" from 1 January 1996 through 31 December 2006
      inclusive. Criteria assessed included demographic characteristics, clinical
      features, symptom duration and treatment initiated by the general practitioner.
      The results of investigations at SCH were reviewed including white blood cell
      count, microbiology and imaging. The presence of complications was determined and
      the results of medical and surgical treatment were assessed. RESULTS: Seventy
      nine episodes of acute mastoiditis were managed in 76 patients. Treatment prior
      to SCH was commenced by the family practitioner or district hospital doctor in
      53/79 patients. The mean duration of community initiated treatment before
      presentation to SCH was 3.7 days. In 33 episodes a previous history of acute
      otitis media was noted (42%). In the remaining 46 episodes (58%) mastoiditis was
      the initial diagnosis. Complications were found in 30 episodes (38%) and 36
      episodes (46%) required surgical treatment. CONCLUSIONS: Mastoiditis often
      develops rapidly but may be treated very effectively. The potential for
      significant morbidity remains high but excellent outcomes can be expected for
      those who are managed without delay. Children with acute mastoiditis should be
      managed in centres where timely and complete medical and surgical treatment is
      available.

PMID- 19758712
TI  - Bile-acid-activated receptors: targeting TGR5 and farnesoid-X-receptor in lipid
      and glucose disorders.
AB  - Bile acids are a family of steroid molecules generated in the liver by
      cholesterol oxidation. In addition to their role in nutrient absorption, bile
      acids are signaling molecules that exert genomic and non-genomic effects by
      activating TGR5 (M-BAR, GP-BAR1 or BG37) a G-protein-coupled receptor, and
      farnesoid X receptor (FXR), a member of the nuclear hormone receptor superfamily.
      Ligands for these receptors might be beneficial in treating disorders of lipid
      and glucose homeostasis. TGR5 ligands decrease blood glucose levels and increase
      energy expenditure by promoting intracellular thyroid hormone activation in
      thermogenically competent tissues. FXR agonists repress the synthesis of
      endogenous bile acids and reduce triglyceride, cholesterol and glucose plasma
      levels and are currently being tested in nonalcoholic steatohepatitis. FXR
      modulators are being developed to target selective gene clusters and avoid the
      negative impact of FXR on HDL biosynthesis. The development of dual FXR and TGR5
      ligands could provide new opportunities for the treatment of lipid and glucose
      disorders.

PMID- 19758713
TI  - From the top down: flexible reading of a fragmented odor map.
AB  - Animals that depend on smell for communication and survival extract multiple
      pieces of information from a single complex odor. Mice can collect information on
      sex, genotype, health and dietary status from urine scent marks, a stimulus made
      up of hundreds of molecules. This ability is all the more remarkable considering
      that natural odors are encountered against varying olfactory backgrounds; the
      olfactory system must therefore provide some mechanism for extracting the most
      relevant information. Here we discuss recent data indicating that the readout of
      olfactory input by mitral cells in the olfactory bulb can be modified by
      behavioral context. We speculate that the olfactory cortex plays a key role in
      tuning the readout of olfactory information from the olfactory bulb.

PMID- 19758715
TI  - Does heart rate predict allograft vasculopathy in heart transplant recipients?
AB  - Experimental data suggest that heart rate is directly associated with the
      progression of atherosclerosis. We evaluated the prognostic importance of heart
      rate measured at rest 3 months after transplantation in 143 heart transplant
      recipients. During the follow-up (mean 9.5 years, range 2-23 years) 56 patients
      had coronary lesions. Survival without coronary lesion at angiography did not
      significantly differ between patients with a basal heart rate > or <=97/min
      (median, p=0.44). This series does not support a prognostic influence of heart
      rate for cardiac allograft vasculopathy.

PMID- 19758714
TI  - Roles for nigrostriatal--not just mesocorticolimbic--dopamine in reward and
      addiction.
AB  - Forebrain dopamine circuitry has traditionally been studied by two largely
      independent specialist groups: students of Parkinson's disease who study the
      nigrostriatal dopamine system that originates in the substantia nigra (SN), and
      students of motivation and addiction who study the role of the mesolimbic and
      mesocortical dopamine systems that originate in the ventral tegmental area (VTA).
      The anatomical evidence for independent nigrostriatal and mesolimbic dopamine
      systems has, however, long been obsolete. There is now compelling evidence that
      both nominal "systems" participate in reward function and addiction. Electrical
      stimulation of both SN and VTA is rewarding, blockade of glutamatergic or
      cholinergic input to either SN or VTA attenuates the habit-forming effects of
      intravenous cocaine, and dopamine in both nigrostriatal and mesocorticolimbic
      terminal fields participates in the defining property of rewarding events: the
      reinforcement of memory consolidation. Thus, the similarities between
      nigrostriatal and mesolimbic dopamine systems can be as important as their
      differences.

PMID- 19758716
TI  - Reply to Sergej V. Jargin: shock wave therapy of ischemic heart disease in the
      light of general pathology.
AB  - Low energy shock wave therapy has developed as a treatment standard or
      alternative therapy for a variety of orthopaedic and soft tissue diseases. In
      experimental studies it shows very promising results for the treatment of
      ischemic heart disease. Sergei V. Jargin reported on a device on the basis of a
      modified lithotripter that is currently used in Russia. He supposes the tissue
      regenerative effect to be an injury-and-repair process, which may end up in
      myocardial function loss. This hypothesis is contradictory to findings of
      numerous research groups. Low energy shock waves show in both clinical and
      experimental studies a safe and highly effective tissue regenerative potential
      that is mediated by various molecular and sub-molecular effects. Therefore low
      energy shock wave therapy is a promising treatment option for ischemic heart
      disease.

PMID- 19758717
TI  - Herd and individual animal risks associated with bovine tuberculosis skin test
      positivity in cattle in herds in south west England.
AB  - The aim of this study was to investigate the cattle-exposure factors associated
      with the risk of a bovine animal reacting to a bovine tuberculosis (bTB) skin
      test at a whole herd test. There were 148 study farms enrolled. These were
      located in six counties of the south west of England in an area considered
      endemic for bovine tuberculosis (bTB): 24% were restocked after foot and mouth
      disease (FMD) in 2001; all farms were located within the Randomised Badger
      Culling Trial (RBCT) area. Data on cattle on these farms were sourced from the
      bTB Vetnet database from 1996 to 2004 and from the British Cattle Movement Scheme
      database. Individual animal records were created that included data on whether or
      not an animal became a reactor at a full-herd bTB test between 1 June 2001 and 19
      August 2004, their prior exposure to cattle with bTB (defined by presence at a
      bTB test where at least one reactor was detected), whether the animal was
      homebred, the farm history of bTB and the farm restocking status. Data from 144
      farms were used, 4 farms had no data. Cattle were more likely to react to the bTB
      skin test when they had been present at a previous bTB herd test (or tests) where
      other cattle had reacted to the skin test. This positively correlated with age
      and the number of bTB tests an animal had had. Cattle on restocked farms were
      less likely to react to the skin test compared with cattle on continuously
      stocked farms. These results highlight the likely importance of exposure to
      infected cattle at a previous test as a source of infection to cattle that
      subsequently became reactors and suggest that there was a lower risk of exposure
      to bTB to cattle in newly formed herds.

PMID- 19758718
TI  - Case control study to investigate risk factors for impaction colic in donkeys in
      the UK.
AB  - Impaction colic is the single most common type of colic diagnosed in a large
      population of donkeys (more than 2000 animals) at The Donkey Sanctuary, UK and
      the fatality rate from the disease is high. Here we identify risk factors for
      impaction colic in this population during 2006 using an unmatched case control
      study. There were 71 cases of impaction colic and multivariable analysis
      identified a number of variables associated with the disease. Management factors
      that increased the risk of impaction included paper bedding, feeding of
      concentrates, limited access to pasture and increasing number of carers. In
      addition health variables that were associated with an increased risk of
      impaction colic were weight loss, recent vaccination and a number of dental
      abnormalities. This study has identified variables which may help to identify
      donkeys at high risk of impaction colic; those with a history of weight loss and
      with concurrent dental pathology. Furthermore the study has also identified a
      number of variables that may be targeted to reduce the incidence of impaction
      colic in this donkey population, such as modification of concentrate feeding
      practices and pasture access.

PMID- 19758719
TI  - Plant biotechnology: the importance of being accurate.

PMID- 19758720
TI  - A pre-clinical assessment of an atlas-based automatic segmentation tool for the
      head and neck.
AB  - BACKGROUND AND PURPOSE: Accurate conformal radiotherapy treatment requires manual
      delineation of target volumes and organs at risk (OAR) that is both time
      consuming and subject to large inter-user variability. One solution is atlas
      based automatic segmentation (ABAS) where a priori information is used to
      delineate various organs of interest. The aim of the present study is to
      establish the accuracy of one such tool for the head and neck (H&N) using two
      different evaluation methods. MATERIALS AND METHODS: Two radiotherapy centres
      were provided with an ABAS tool that was used to outline the brainstem, parotids
      and mandible on several patients. The results were compared to manual
      delineations for the first centre (EM1) and reviewed/edited for the second centre
      (EM2), both of which were deemed as equally valid gold standards. The contours
      were compared in terms of their volume, sensitivity and specificity with the
      results being interpreted using the Dice similarity coefficient and a receiver
      operator characteristic (ROC) curve. RESULTS: Automatic segmentation took
      typically approximately 7min for each patient on a standard PC. The results
      indicated that the atlas contour volume was generally within +/-1SD of each gold
      standard apart from the parotids for EM1 and brainstem for EM2 that were over-
      and under-estimated, respectively (within +/-2SD). The similarity of the atlas
      contours with their respective gold standard was satisfactory with an average
      Dice coefficient for all OAR of 0.68+/-0.25 for EM1 and 0.82+/-0.13 for EM2. All
      data had satisfactory sensitivity and specificity resulting in a favourable
      position in ROC space. CONCLUSIONS: These tests have shown that the ABAS tool
      exhibits satisfactory sensitivity and specificity for the OAR investigated. There
      is, however, a systematic over-segmentation of the parotids (EM1) and under
      segmentation of the brainstem (EM2) that require careful review and editing in
      the majority of cases. Such issues have been discussed with the software
      manufacturer and a revised version is due for release.

PMID- 19758721
TI  - Modulated electron radiotherapy treatment planning using a photon multileaf
      collimator for post-mastectomized chest walls.
AB  - BACKGROUND AND PURPOSE: To evaluate the feasibility of using a photon MLC (xMLC)
      for modulated electron radiotherapy treatment (MERT) as an alternative to
      conventional post-mastectomy chest wall (CW) irradiation. A Monte Carlo (MC)
      based planning system was developed to overcome the inaccuracy of the 'pencil
      beam' algorithm. MC techniques are known to accurately calculate the dose
      distributions of electron beams, allowing the explicit simulation of electron
      interactions within the MLC. MATERIALS AND METHODS: Four real clinical CW cases
      were planned using MERT which were compared with the conventional electron
      treatments based on blocks and by a straightforward approach using the MLC, and
      not the blocks (as an intermediate step to MERT) to shape the same segments with
      SSD between 60 and 70 cm depending on PTV size. MC calculations were verified
      with an array of ionization chambers and radiochromic films in a solid water
      phantom. RESULTS: Tests based on gamma analysis between MC dose distributions and
      radiochromic film measurements showed an excellent agreement. Differences in the
      absolute dose measured with a plane-parallel chamber at a reference point were
      below 3% for all cases. MERT solution showed a better PTV coverage and a
      significant reduction of the doses to the organs at risk (OARs). CONCLUSION: MERT
      can effectively improve the current electron treatments by obtaining a better PTV
      coverage and sparing healthy tissues. More directly, block-shaped treatments
      could be replaced by MLC-shaped non-modulated segments providing similar results.

PMID- 19758722
TI  - A hands-on approach for fitting long-term survival models under the GAMLSS
      framework.
AB  - In many data sets from clinical studies there are patients insusceptible to the
      occurrence of the event of interest. Survival models which ignore this fact are
      generally inadequate. The main goal of this paper is to describe an application
      of the generalized additive models for location, scale, and shape (GAMLSS)
      framework to the fitting of long-term survival models. In this work the number of
      competing causes of the event of interest follows the negative binomial
      distribution. In this way, some well known models found in the literature are
      characterized as particular cases of our proposal. The model is conveniently
      parameterized in terms of the cured fraction, which is then linked to covariates.
      We explore the use of the gamlss package in R as a powerful tool for inference in
      long-term survival models. The procedure is illustrated with a numerical example.

PMID- 19758723
TI  - EUS-FNA in the preoperative staging of non-small cell lung cancer.
AB  - BACKGROUND: According to current guidelines, transesophageal ultrasound-guided
      fine needle aspiration (EUS-FNA) can be performed as an alternative for surgical
      staging to confirm mediastinal metastases in patients with non-small cell lung
      cancer (NSCLC). To date however, data regarding the routine use of EUS-FNA in the
      preoperative staging of unselected patients with NSCLC are limited. AIMS AND
      OBJECTIVES: (1) To evaluate the diagnostic value of EUS-FNA in consecutive,
      patients with NSCLC regardless of nodal size at CT. (2) To determine the impact
      of EUS-FNA on the prevention of surgical staging procedures. (3) To assess the
      accuracy of mediastinal staging by combining EUS-FNA and mediastinoscopy. (4) To
      investigate whether a subgroup of patients exists that can be accurately staged
      by EUS-FNA alone. METHODS: 152 consecutive operable patients with proven or
      suspected NSCLC who underwent EUS-FNA were retrospectively analyzed. In the
      absence of mediastinal metastases, mediastinoscopy and/or thoracotomy with lymph
      node dissection was performed. RESULTS: The prevalence of mediastinal metastases
      was 49%. Sensitivity, negative predictive value (NPV) and accuracy of EUS-FNA for
      N2/N3 disease were 74%, 73% and 85% respectively, whereas these values for the
      combined staging of EUS-FNA and mediastinoscopy were 92%, 85% and 95%. Additional
      surgical staging in patients staged N0 at EUS-FNA reduces the false negative EUS
      findings by 55%. The NPV of EUS-FNA for left-sided tumors was 68%. EUS-FNA
      prevented surgical staging procedures in 60 of 152 patients (39%). No major
      complications occurred during EUS-FNA. CONCLUSION: Routine use of EUS-FNA in
      unselected patients with NSCLC reduces the need for surgical staging procedures
      in nearly half of patients. Additional surgical staging in patients without nodal
      metastases at EUS-FNA reduces the false negative EUS-FNA findings considerably
      regardless of the location of the primary lung tumor.

PMID- 19758724
TI  - Scaling up from gardens: biodiversity conservation in urban environments.
AB  - As urbanisation increases globally and the natural environment becomes
      increasingly fragmented, the importance of urban green spaces for biodiversity
      conservation grows. In many countries, private gardens are a major component of
      urban green space and can provide considerable biodiversity benefits. Gardens and
      adjacent habitats form interconnected networks and a landscape ecology framework
      is necessary to understand the relationship between the spatial configuration of
      garden patches and their constituent biodiversity. A scale-dependent tension is
      apparent in garden management, whereby the individual garden is much smaller than
      the unit of management needed to retain viable populations. To overcome this,
      here we suggest mechanisms for encouraging 'wildlife-friendly' management of
      collections of gardens across scales from the neighbourhood to the city.

PMID- 19758725
TI  - Transcriptional effects of colony-stimulating factor-1 in mouse macrophages.
AB  - Colony-stimulating factor-1 (CSF-1) is a major regulator of macrophage
      development. CSF-1-dependent signalling has been implicated in proliferation,
      survival, and differentiation of mononuclear phagocytes, however, relatively
      little is known about the effects of CSF-1 on macrophage gene transcription and
      on CSF-1-responsive gene promoters. We used a combination of transcription
      profiling and in silico motif search to characterize genes that are regulated in
      mature bone marrow-derived macrophages cultured in the presence or absence of CSF
      1. The expression of many known differentiation-associated macrophage markers was
      not significantly affected in the absence of CSF-1. Genes repressed by CSF-1
      comprised a considerable number of granulocyte-specific genes. The respective
      gene promoters; however, were not significantly enriched for specific DNA
      patterns, suggesting that these genes are regulated by promoter-distal elements
      or at a post-transcriptional level. Genes downregulated upon CSF-1 deprivation
      showed a highly significant association with cell division which is in line with
      the known role of CSF-1 as a proliferation stimulus for mouse macrophages.
      Interestingly, three DNA patterns were significantly co-enriched in CSF-1
      dependent gene promoters, including motifs related to NFY, CHR, and E2F sites.
      These motifs showed a strong positional preference on target promoters at -60, 
      30 and 0 bp upstream of the transcription start site, and define the common
      promoter structure of CSF-1-responsive genes.

PMID- 19758726
TI  - Genetic engineering of novel flower colour by suppression of anthocyanin
      modification genes in gentian.
AB  - Ornamental gentian plants have vivid-blue flowers. The main factor contributing
      to the flower colour is the accumulation of a polyacylated delphinidin
      'gentiodelphin' in their petals. Although in vitro studies proposed that
      acylation plays an important role in the stability and development of gentian
      blue colour, the in vivo stability of the polyacylated anthocyanin was not
      clearly demonstrated. Thus, to reveal the importance of anthocyanin modification,
      especially acylation, and to engineer new colours of gentian flowers, we used
      chimeric RNAi technology to produce transgenic gentian plants with downregulated
      anthocyanin 5,3'-aromatic acyltransferase (5/3'AT) and flavonoid 3',5'
      hydroxylase (F3'5'H) activities, which are both essential enzymes for
      gentiodelphin biosynthesis. Two lines of flower colour-modified plants were
      obtained from fifteen transgenic gentian plants. Clone no. 1 exhibited a lilac
      flower colour and clone no. 15 exhibited pale-blue flowers. RNA gel blot analysis
      confirmed that both transgenic lines had markedly suppressed 5/3'AT transcripts,
      whereas clone no. 15 had fewer F3'5'H transcripts than clone no. 1 and
      untransformed control plants. HPLC analysis of anthocyanin compositions showed
      that downregulation of the 5/3'AT gene led to increased accumulation of non
      acylated anthocyanins, as expected. These results demonstrated that genetic
      engineering to reduce the accumulation of polyacylated anthocyanins could cause
      modulations of flower colour.

PMID- 19758727
TI  - [Endogenous cannabinoids in liver disease: Many darts for a single target].
AB  - Endogenous cannabinoids are ubiquitous lipid-signaling molecules able to
      partially mimic the actions produced by Delta(9)-tetrahydrocannabinol, the
      compound responsible for most of the psychological effects of marijuana.
      Endocannabinoids are derived from arachidonic acid and are involved in many
      physiological effects. This family of substances includes anandamide
      (arachidonylethanolamide), 2-arachydonylglycerol, noladin ether and virodhamine.
      The interaction of these substances with CB1 and CB2 receptors results in most of
      their biological effects. The endocannabinoid system is involved in the
      pathogenesis of the cardiovascular dysfunction occurring in advanced liver
      disease and also plays a role in the pathogenesis of portal hypertension and
      liver fibrosis. Moreover, this system is also altered in other processes
      associated with hepatic dysfunction, including encephalopathy, obesity and
      steatosis. These findings indicate that the endocannabinoid system may open new
      avenues for the therapeutic regulation of fibrosis and portal hypertension in
      advanced liver disease.

PMID- 19758728
TI  - Biological activity studies on metal complexes of novel tridentate Schiff base
      ligand. Spectroscopic and thermal characterization.
AB  - Metal complexes of novel Schiff base (HL) ligand, prepared via condensation of 4
      aminoantipyrine and 2-aminophenol, are prepared. The ligand is characterized
      based on elemental analysis, mass, IR and (1)H NMR spectra. Metal complexes are
      reported and characterized based on elemental analyses, IR, (1)H NMR, solid
      reflectance, magnetic moment, molar conductance, ESR spectra and thermal analyses
      (TG, DTG and DTA). From the elemental analyses, 1:1 [M]:[ligand] complexes are
      prepared with the general formulae [M(L)Cl(H(2)O)(2)] x yH(2)O (M = Mn(II),
      Co(II), Ni(II), Cu(II), Zn(II) and Cd(II), y = 3-4), [Fe(L)Cl(2)(H(2)O)] x 3
      H(2)O and [Th(L)Cl(H(2)O)(2)]Cl(2) x 3 H(2)O. The molar conductance data reveal
      that all the metal chelates are non-electrolytes (except Th(IV) complex, it is
      2:1 electrolyte). IR spectra show that HL is coordinated to the metal ions in a
      uninegatively tridentate manner with NNO donor sites of the azomethine-N, amino N
      and deprotonated phenolic-O. From the magnetic and solid reflectance spectra, it
      is found that the geometrical structures of these complexes are octahedral. The
      thermal behaviour of these chelates shows that the hydrated complexes losses
      water molecules of hydration in the first step followed immediately by
      decomposition of the anions and ligand molecules in the subsequent steps. The
      activation thermodynamic parameters are calculated from the DTG curves using
      Coats-Redfern method. The synthesized ligand, in comparison to its metal
      complexes is screened for its antibacterial activity against bacterial species,
      Escherichia coli, Pseudomonas putida, Exiguobacterium acetylicum and Bacillus
      simplex. The activity data show that the metal complexes to be more
      potent/antibacterial than the parent Schiff base ligand against one or more
      bacterial species.

PMID- 19758729
TI  - Researching student absence: methodological challenges and ethical issues.
AB  - This article describes the challenges encountered in a research project aiming to
      explore non-attendance from the perspective of absent students. These students
      are nursing students in a Faculty of Health and Social Care, but the issues
      raised here are of wider interest. Although attendance at the sessions monitored
      for this project is stated to be compulsory, there is typically a non-attendance
      rate of around 20%. Previous studies within the Faculty have reported positively
      on students' views of the sessions, but have relied on data collected from
      students present in the university and attending the sessions. We felt it was
      important to correct this imbalance with the views of those students who do not
      attend. We hoped to access the views of students not present in the university by
      means of telephone interviews, carried out by a researcher independent from the
      course management. This article explores a number of ethical and methodological
      issues which arose from the research, focusing on the difficulties in gaining
      informed consent from students who do not attend, and the challenges in moving
      beyond surface responses to questions on reasons for non-attendance.

PMID- 19758730
TI  - Gender, gender roles and completion of nursing education: a longitudinal study.
AB  - The current worldwide nursing shortage and high attrition of nursing students
      remain a challenge for the nursing profession. The aim of this paper was to
      investigate how key psychological attributes and constructions differentiate
      between completers and non-completers of nursing education. A questionnaire
      including measures of gender role identity and perceived gender appropriateness
      of careers was administered to 384 students early in the first year of the
      course. At the end of the programme attrition rates were obtained. The findings
      indicate that males were more likely to leave the course than females.
      Furthermore, those who completed the course tended to view nursing as more
      appropriate for women, in contrast to the non-completers who had less gender
      typed views. The female-dominated nature of nursing, prevalent stereotypes and
      gender bias inherent in nursing education seem to make this an uncomfortable
      place for males and those with less gendered typed views. Whilst it is
      acknowledged that attrition is undoubtedly a complex issue with many contributing
      factors, the nursing profession need to take steps to address this bias to ensure
      their profession is open equally to both female and male recruits.

PMID- 19758731
TI  - Improving cross-cultural care and antiracism in nursing education: a literature
      review.
AB  - PURPOSE: To appraise through literature review the available research evidence to
      guide teaching and learning regarding cross-cultural care for nursing students.
      Cross-cultural education of nurses with a focus on both culture and antiracism is
      one way of promoting ethical and effective cross-cultural health systems for
      people from culturally diverse backgrounds. Although cross-cultural care has long
      been recognised as necessary to nursing education there is no clear consensus
      regarding how it is to be taught or which theoretical perspectives should
      underpin this teaching. FINDINGS: Current literature supports the effectiveness
      of cross-cultural teaching interventions in promoting cultural competence and in
      facilitating attitudinal and belief changes in nursing students. The literature
      further suggests that racism persists in some students following participation in
      cross-cultural education and that there is a paucity of theory, teaching
      interventions and evaluations addressing antiracism. CONCLUSIONS: Cross-cultural
      education alone is insufficient to combat racism. Cross-cultural education
      focused on both cultural competence and antiracism is necessary to promote
      effective cultural care in nursing students.

PMID- 19758732
TI  - Extension of sensitivity and uncertainty analysis for long term dose assessment
      of high level nuclear waste disposal sites to uncertainties in the human
      behaviour.
AB  - Biosphere dose conversion factors are computed for the French high-level
      geological waste disposal concept and to illustrate the combined probabilistic
      and deterministic approach. Both (135)Cs and (79)Se are used as examples.
      Probabilistic analyses of the system considering all parameters, as well as
      physical and societal parameters independently, allow quantification of their
      mutual impact on overall uncertainty. As physical parameter uncertainties
      decreased, for example with the availability of further experimental and field
      data, the societal uncertainties, which are less easily constrained, particularly
      for the long term, become more and more significant. One also has to distinguish
      uncertainties impacting the low dose portion of a distribution from those
      impacting the high dose range, the latter having logically a greater impact in an
      assessment situation. The use of cumulative probability curves allows us to
      quantify probability variations as a function of the dose estimate, with the
      ratio of the probability variation (slope of the curve) indicative of
      uncertainties of different radionuclides. In the case of (135)Cs with better
      constrained physical parameters, the uncertainty in human behaviour is more
      significant, even in the high dose range, where they increase the probability of
      higher doses. For both radionuclides, uncertainties impact more strongly in the
      intermediate than in the high dose range. In an assessment context, the focus
      will be on probabilities of higher dose values. The probabilistic approach can
      furthermore be used to construct critical groups based on a predefined
      probability level and to ensure that critical groups cover the expected range of
      uncertainty.

PMID- 19758733
TI  - Creutzfeldt-Jakob disease affecting the maxillofacial region: a case report.
AB  - Creutzfeldt-Jakob disease (CJD) is a rare disorder caused by prions that can
      affect any part of the central nervous system. It is characterised by an initial
      non-specific illness of varying duration, followed by progressive neurological
      decline. We report a patient with sporadic CJD who presented with neurological
      symptoms and bilateral dislocation of the temporomandibular joints (TMJs). To our
      knowledge this is the first report of sporadic CJD that involved the
      maxillofacial region.

PMID- 19758734
TI  - Veterinary and radiological evaluations of open and closed treatment of type B
      diacapitular (intracapsular) fractures of the mandibular condyle in sheep.
AB  - The incidence of diacapitular (intracapsular) fractures of the mandibular condyle
      has increased in recent years, but their treatment remains inadequate,
      particularly of type B fractures. To evaluate and compare outcomes of open and
      closed treatments we created a sheep model of a type B fracture through an
      osteotomy. Eight sheep were randomly divided into two groups of four each to be
      given closed treatment or open reduction and internal fixation (ORIF) and were
      evaluated by veterinary and radiological examinations. Compared with before the
      osteotomy, there were significant reductions in maximum mouth opening (MMO) and
      left movement in the closed group, but no significant differences in the range of
      jaw movements in the ORIF group after 12 weeks of treatment. The two radiological
      scores that indicated the degree of osteoarthrotic changes and ankylosis of the
      temporomandibular joint (TMJ) in the ORIF group were significantly lower than
      those in the closed group. Anatomical observation confirmed the pathological
      changes in the right TMJ in the closed group and adaptive changes in the ORIF
      group. We conclude that ORIF is more efficient than closed treatment in restoring
      the function and shape of the TMJ to after a type B diacapitular condylar
      fracture.

PMID- 19758735
TI  - The effect of valgus bracing on the knee adduction moment during gait and running
      in male subjects with varus alignment.
AB  - BACKGROUND: Increased mechanical load is one risk factor for osteoarthritis. One
      possible treatment for this disorder is the use of knee braces in order to
      redistribute joint loading, which may inhibit the progression of the disease. The
      hypothesis was: knee adduction moment can be reduced with the use of a dedicated
      knee orthosis, which applies an abduction moment at the knee. METHODS: Sixteen
      healthy male subjects with varus alignment were analysed during walking and
      running while using an adjustable valgus orthosis. Peak knee adduction moments
      and knee adduction angular impulses were evaluated through inverse dynamics.
      Additionally, the abduction moment produced by the orthosis was measured in three
      different adjustments of valgus angulations (neutral, 4 degrees and 8 degrees
      valgus) using a strain gauge device. FINDINGS: During walking, mean reductions of
      25% and 36% in the knee adduction angular impulse were found between the
      conditions without orthosis and 4 degrees and between without orthosis and 8
      degrees, respectively. For the running trials mean reductions of 18% and 23% were
      observed between these same conditions. The first and second peak knee adduction
      moments also decreased during walking with different orthosis adjustments
      (changes from 5% to 33%). During running, a significant reduction was observed
      only between the conditions without orthosis and 8 degrees valgus adjustments
      (change of 11%). INTERPRETATION: The orthosis tested in this study was effective
      in reducing the knee adduction moments during walking and running. This reduction
      of knee adduction moments during locomotion should contribute to decelerate
      osteoarthritis progression.

PMID- 19758736
TI  - Governing childhood obesity: framing regulation of fast food advertising in the
      Australian print media.
AB  - Childhood obesity is widely constructed as reaching epidemic proportions with
      consumption of fast food viewed as a contributing factor. This paper analyses
      media reporting of the regulation of fast food consumption to children. A media
      search of five Australian newspapers for the period January 2006 to June 2008
      elicited 100 articles relating to the regulation of fast food advertising to
      children. Content and thematic analysis of the articles reveal conflicting
      perspectives on the role of the state; the level of accountability of the food
      and advertising industries; and responsibilities of parents for regulating fast
      food consumption in children. The Federal Government, food and advertising
      industries and free to air broadcasters favour industry self-regulation and
      personal responsibility for fast food consumption while the proponents of
      government regulation include consumer groups, state government health ministers,
      nutrition and public health academics and medical and health foundations. The
      regulation of fast food advertising to children is discussed in relation to ideas
      about governance and the public health strategies which follow from these ideas.
      The paper argues that all proposed solutions are indicative of a neoliberal
      approach to the governance of health insofar as the responsibility for regulation
      of food marketing is viewed as lying with industry and the regulation of
      lifestyle risk is viewed as an individual responsibility.

PMID- 19758737
TI  - A model of mother-child adjustment in Arab Muslim immigrants to the US.
AB  - We examined the mother-child adjustment and child behavior problems in Arab
      Muslim immigrant families residing in the U.S.A. The sample of 635 mother-child
      dyads was comprised of mothers who emigrated from 1989 or later and had at least
      one early adolescent child between the ages of 11 and 15 years old who was also
      willing to participate. Arabic speaking research assistants collected the data
      from the mothers and children using established measures of maternal and child
      stressors, coping, and social support; maternal distress; parent-child
      relationship; and child behavior problems. A structural equation model (SEM) was
      specified a priori with 17 predicted pathways. With a few exceptions, the final
      SEM model was highly consistent with the proposed model and had a good fit to the
      data. The model accounted for 67% of the variance in child behavior problems.
      Child stressors, mother-child relationship, and maternal stressors were the
      causal variables that contributed the most to child behavior problems. The model
      also accounted for 27% of the variance in mother-child relationship. Child active
      coping, child gender, mother's education, and maternal distress were all
      predictive of the mother-child relationship. Mother-child relationship also
      mediated the effects of maternal distress and child active coping on child
      behavior problems. These findings indicate that immigrant mothers contribute
      greatly to adolescent adjustment, both as a source of risk and protection. These
      findings also suggest that intervening with immigrant mothers to reduce their
      stress and strengthening the parent-child relationship are two important areas
      for promoting adolescent adjustment.

PMID- 19758738
TI  - A "usual occurrence:" stress incontinence among reproductive aged women in Sri
      Lanka.
AB  - Stress urinary incontinence (SUI) is a common condition among women of all ages,
      often with devastating consequences, such as depression, anxiety and reduced
      quality of life. Researchers have largely focused on its prevalence and clinical
      management, particularly in highly industrialized country settings. In this
      article, drawing on epidemiological, clinical and qualitative research undertaken
      in Sri Lanka, we discuss how stress incontinence affects women's lives and how
      they personally manage the problem. Quantitative data derive from a community
      based descriptive cross-sectional study, conducted in 2006-2007 with 1718 ever
      married women, aged 15-49, of whom 9.8% reported problems of stress incontinence.
      Six focus group discussions, eight key informant interviews and five case studies
      with women with SUI were also undertaken to gain insight and depth. Although
      incontinence affected outdoor activities, sexual life, and sense of wellbeing,
      women did not consider it a health problem, rarely discussed it with others, and
      rarely sought treatment. Barriers to help seeking included fear of vaginal
      examination, shame and embarrassment, and belief that SUI was a natural
      consequence of aging and childbirth. Women's reluctance to seek advice on their
      own initiative about managing incontinence indicates the importance for health
      providers to pay greater attention to the condition and introduce appropriate
      preventive measures for women. This might include creating greater public
      awareness of SUI as preventable and treatable, ensuring a clinical environment
      conducive to discussing problems related to bodily functions.

PMID- 19758739
TI  - [Analyzing the economy, something is changing concerning asthma].

PMID- 19758740
TI  - [The new A/H1N1 influenza: a pandemic with a great many protagonists].

PMID- 19758741
TI  - [Pulmonary haemorrhage and haemothorax after massive ingestion of clopidogrel as
      a suicide attempt].

PMID- 19758742
TI  - [Care results in a specialist stop-smoking unit].
AB  - BACKGROUND AND OBJECTIVE: To present the short, medium and long-term results of a
      stop-smoking clinic after 5 years of experience. The clinic was designed
      following the SEPAR Recommendations. PATIENTS AND METHODS: Two types of clinic
      protocols have been applied: individual and group. Both included the offer of a
      combination of psychological intervention and pharmacological treatment. The
      programme included 10 visits over 12 months. The pharmacological treatment
      consisted of: nicotine replacement therapy (NRT) or bupropion or varenicline or a
      combination. The psychological intervention consisted of: self-monitoring,
      copying skills, cognitive-behavioural therapy and social intra-treatment support.
      The treatment was always offered for free. RESULTS: A total of 3920 patients were
      seen in the clinic. These patients made 21,418 clinic visits. The analysis was
      performed on the 1850 smokers who attended the clinic consecutively. Their mean
      age was 47.83 (+/-11.03) and the mean fagerstrom test for nicotine dependence
      (FTND)-score was 6.56 (+/-2.41). 55.9% patients received NRT, 22.8% bupropion,
      18.9% varenicline and 2.4% did not receive any pharmacological treatment.
      Continuous abstinence rates at 6 and 12 months follow up were 58.5% and 54.9%,
      respectively. These abstinence rates at 36 and 57 months follow up were 42% and
      35%, respectively. The cost in medication for each patient was 118 euros and the
      cost in medication for a successful abstainer at 6, 12, 36, and 57 months of
      follow up were 202, 215, 281 and 338 euros, respectively. CONCLUSIONS: A stop
      smoking clinic that is designed according to SEPAR Recommendations is effective
      and has a good cost/effective ratio.

PMID- 19758743
TI  - [Clinical perspective as seen in Archivos de Bronconeumologia].
AB  - This article discusses the current main clinical problems of thoracic surgery and
      pneumology by means of the articles published in 2008 in the "clinical notes"
      section of the journal Archivos de Bronconeumologia. The 18 cases published 
      which deal with topics ranging from pharmacologic toxicity to lung function- will
      enable us to discuss the main novelties in each one of the various fields and
      highlight future areas for research.

PMID- 19758744
TI  - XIAP gene downregulation by small interfering RNA inhibits proliferation, induces
      apoptosis, and reverses the cisplatin resistance of ovarian carcinoma.
AB  - OBJECTIVE: XIAP is one of the most important members of the inhibitors of
      apoptosis family. It is upregulated in various malignancies, including human
      ovarian carcinomas, it promotes invasion, metastasis, growth, and survival of
      malignant cells, and it also confers resistance to some chemotherapeutic drugs.
      We observed the effect of XIAP gene RNA interference (RNAi) on the proliferation,
      apoptosis, tumorigenicity, and chemosensitivity of the human ovarian carcinoma
      cells A2780/cp70. STUDY DESIGN: We used a human U6 promoter-driven DNA template
      approach to induce short hairpin RNA-triggered RNAi to block XIAP gene expression
      in the human ovarian cancer cell line A2780/cp70. A corresponding site-mutated
      vector was constructed as a negative control (pSilencer 2.1-NC). The expression
      of XIAP mRNA and protein among the stable transfected cells and the untransfected
      ones was detected by RT-PCR and Western blotting. The cell growth was examined
      and drug sensitivity was assayed using the MTT assay. Cell apoptosis was measured
      by flow cytometry and the tumorigenicity by using nude mice. RESULTS: Three
      stable transfected cell lines: A2780/cp70-s2, A2780/cp70-NC, and A2780/cp70-neo
      were established. The expression levels of XIAP gene mRNA and protein in
      A2780/cp70-s2 were 63.3% and 60.8%, lower than in A2780/cp70-NC, A2780/cp70-neo,
      and untransfected A2780/cp70 cells. The cell proliferation of A2780/cp70-s2 was
      reduced by up to 62.2+/-1.9%. Compared with the other cell lines, the changes in
      apoptotic rate in A2780/cp70-s2 was 31.1+/-1.3%, obviously increasing (P<0.05).
      The knockdown of XIAP retards tumorigenicity in nude mice and after 21 days the
      average tumor weight of the A2780/cp70-s2 group was lower by 1.62+/-0.11g
      (P<0.05). And the survival index in A2780/cp70-s2 cells was markedly reduced with
      the addition of 1 microM and 10 microM cisplatinum, respectively (P<0.05).
      CONCLUSIONS: XIAP gene RNAi inhibited the proliferation of ovarian carcinoma
      cells and caused cells to be more sensitive to cisplatin through the reduction of
      its mRNA and protein. These results suggest that XIAP is an ovarian cancer
      related gene and that XIAP is a potential target for therapeutic anti-cancer
      drugs.

PMID- 19758745
TI  - Pesticide tolerance of Paenibacillus sp. D1 and its chitinase.
AB  - Excessive use of pesticides in agriculture has led to several problems pertaining
      to loss of soil fertility and environmental degradation. Biological control
      agents offer the best alternative to reduce use of toxic pesticides.
      Paenibacillus sp. D1 isolated from the effluent treatment plant of a seafood
      processing industry exhibited broad spectrum tolerance towards a number of
      pesticides at concentrations higher than recommended for field applications. The
      isolate showed enhanced growth and chitinase production in the presence of some
      protectant fungicides. None of the tested demethylase inhibitor (DMI) fungicides
      inhibited growth and chitinase production except triadimefon. The isolate was
      also tolerant to most commonly used insecticides belonging to the
      organophosphate, carbamate and cyclodiene organochloride classes. Chitinase of
      Paenibacillus sp. D1 was found to be more tolerant than the organism itself and
      was highly stable in the presence of pesticides at the temperature under field
      conditions in Gujarat, India, i.e. 40 degrees C. This was suggestive of its
      potential in integrated pest management (IPM) to significantly reduce the use of
      harmful chemicals. To our knowledge this is the first extensive study on
      pesticide tolerance of the Paenibacillus species and its chitinase.

PMID- 19758746
TI  - Platinum (IV) recovery from chloride solution by functionalized acrylic
      copolymers.
AB  - Two acrylic adsorbents with different morphological structures and bearing
      amidoethylenamine and thiol groups were obtained and used for platinum sorption
      from chloride solution by the batch method. Physico-chemical parameters that
      influence adsorption such as initial Pt(IV) concentration, stirring time, pH, and
      adsorbent amount were investigated. The thermodynamic parameters of Pt(IV)
      sorption on the synthesized adsorbent were also evaluated based on Langmuir and
      Freundlich isotherms. Thermodynamic parameters estimated from Langmuir constants
      indicated that the adsorption is spontaneous, exothermic and there is a
      disordered state at the molecular level. The models used to analyze the sorption
      rate led to the conclusion that the most important step in the sorption of Pt(IV)
      could be both particle diffusion and chemical reaction of [PtCl(6)](-) with amine
      functional groups. Thus, both the ion exchange and complex formation mechanisms
      can occur via nitrogen atoms in the recovery of Pt(IV) on the studied adsorbent.

PMID- 19758748
TI  - An unusual DNA binding compound, S23906, induces mitotic catastrophe in cultured
      human cells.
AB  - The biochemical pathways that lead cells to mitotic catastrophe are not well
      understood. To identify these pathways, we have taken an approach of treating
      cells with a novel genotoxic compound and characterizing whether cells enter
      mitotic catastrophe or not. S23906 is a novel acronycine derivative that forms
      adducts with the N2 residue of guanine in the minor groove of the DNA helix and
      destabilizes base pairing to cause helix opening. We observed, in HeLa and HT-29
      cells, that S23906 induced gamma-H2AX and activated checkpoint kinase 1, as did
      bleomycin, camptothecin, and cisplatin, when tested under equi-toxic conditions.
      S23906 also induced cyclin E1 protein, although this activity was not required
      for cytotoxicity because knock down of cyclin E1 by RNA interference did not
      affect the number of dead cells after treatment. Cyclin B1 levels first decreased
      and then increased after treatment with S23906. Cyclin B1 was associated with
      Cdk1 kinase activity, which correlated with an increase in the number of mitotic
      cells. By 32 h after treatment, at least 20% of the cells entered mitotic
      catastrophe as determined by microscopy. Suppression of the DNA checkpoint
      response by co-treatment with caffeine increased the number of cells in mitosis.
      These results suggest that mitotic catastrophe is one of the cellular responses
      to S23906 and that mitotic catastrophe may be a common cellular response to many
      different types of DNA damage.

PMID- 19758749
TI  - Removal and preconcentration of lead (II), copper (II), chromium (III) and iron
      (III) from wastewaters by surface developed alumina adsorbents with immobilized 1
      nitroso-2-naphthol.
AB  - The potential removal and preconcentration of lead (II), copper (II), chromium
      (III) and iron (III) from wastewaters were investigated and explored. Three new
      alumina adsorbents of acidic, neutral and basic nature (I-III) were synthesized
      via physical adsorption and surface loading of 1-nitroso-2-naphthol as a possible
      chelating ion-exchanger. The modified alumina adsorbents are characterized by
      strong thermal stability as well as resistance to acidic medium leaching
      processes. High metal up-take was found providing this order:
      Cu(II)>Cr(III)>Pb(II) owing to the strong contribution of surface loaded 1
      nitroso-2-naphthol. The outlined results from the distribution coefficient and
      separation factor evaluations (low metal ion concentration levels) were found to
      denote to a different selectivity order: Pb(II)>Cu(II)>Cr(III)) due to the strong
      contribution of alumina matrix in the metal binding processes. The potential
      applications of alumina adsorbents for removal and preconcentration of Pb(II),
      Cu(II), Cr(III) from wastewaters as well as drinking tap water samples were
      successfully accomplished giving recovery values of (89-100+/-1-3%) and (93-99+/
      3-4%), respectively without any noticeable interference of the wastewater or
      drinking tap water matrices.

PMID- 19758750
TI  - Energetic residues from field disposal of gun propellants.
AB  - Military training with howitzers and mortars produces excess propellant that is
      burned on the training range and can result in point sources containing high
      concentrations of unreacted propellant constituents. Propellants contain
      energetic compounds such as nitroglycerin (NG) and 2,4-dinitrotoluene (2,4-DNT),
      both of which are found at firing positions and propellant disposal areas. To
      quantify the mass of residue remaining from the field-expedient disposal of
      propellants, two mortar propellants and one howitzer propellant were burned under
      different field conditions. These conditions included burning on a snow pack, at
      the bottom of a snow pit, and in a pan surrounded by snow for the mortar
      propellants and on dry and wet sand for the howitzer propellant. For the mortar
      propellant, the energetics (NG) remaining after burning in the bowl, on frozen
      ground, and on snow were 0.21%, 5.2% and 18%, respectively. For the howitzer
      propellant, the difference in energetics (2,4-DNT) remaining after disposal on
      wet and dry sand was <0.1%, with the overall residue rate of around 1%, similar
      to that for the mortar propellant burned in an open container. These tests
      demonstrate that environmental factors, especially in winter, can play a
      significant role in the effectiveness of field-expedient disposal of propellants.

PMID- 19758751
TI  - Remediation of polluted soil by a two-stage treatment system: desorption of
      phenanthrene in soil and electrochemical treatment to recover the extraction
      agent.
AB  - In this study, the feasibility of a two-stage treatment process for the
      remediation of soil contaminated with phenanthrene as a model polycyclic aromatic
      hydrocarbon (PAH) has been assessed at laboratory scale. The initial stage of the
      process involved contacting contaminated soil with a solution of Tween 80 to
      enhance the desorption of phenanthrene from soil. In order to simulate a flushing
      process this initial stage was carried out in a washing packed-bed soil column.
      At the optimised conditions the total phenanthrene removal attained a value of
      almost 65% after 3 days. The second stage of the suggested treatment involved
      regeneration of the washing solution via phenanthrene degradation. The use of an
      electrochemical treatment was proposed for surfactant recovery and degradation of
      contaminants present in the solution collected. This oxidation was accomplished
      via an electrochemical cell by using graphite as electrode material. The
      phenanthrene was almost totally degraded in 3 days, reaching a degradation of
      about 96%. In addition, a test in which this regenerated solution was employed in
      the washing process was carried out in shake flask and washing column. The
      results demonstrate that selective degradation of pollutants by electrochemical
      treatment is potentially effective in reusing surfactant in another polluted soil
      treatment.

PMID- 19758752
TI  - Degradation of p-nitrophenol using acoustic cavitation and Fenton chemistry.
AB  - Due to increasing human requirements, newer chemical species are being observed
      in the effluent streams with higher loadings such that efficacy of conventional
      treatment techniques is decreased and a combination of advanced oxidation
      processes is implemented for enhanced treatment ability and better energy
      efficiency. In the present work, the efficacy of combination of sonochemistry and
      Fenton chemistry has been investigated for wastewater treatment considering p
      nitrophenol as model pollutant at pilot scale operation. Degradation of p
      nitrophenol has been investigated under various operating conditions based on the
      use of ultrasound, Fenton process, ultrasound and H(2)O(2), ultrasound and Fe,
      ultrasound and FeSO(4), ultrasound and conventional Fenton process and ultrasound
      and advanced Fenton process. Two different initial concentrations of 0.5 and 1%
      of p-nitrophenol have been used for the experiments. In conventional Fenton and
      advanced Fenton process, two loadings of FeSO(4) and Fe powder 0.5 and 1g/l and
      three ratios of FeSO(4):H(2)O(2) and Fe:H(2)O(2) (1:5, 1:7.5 and 1:10) were
      investigated respectively. In all the systems investigated, maximum extent of
      degradation (66.4%) was observed for 0.5% p-nitrophenol concentration (w/v) using
      a combination of ultrasound and advanced Fenton process. The novelty of the work
      is in terms of investigating the efficacies of combined advanced oxidation
      processes based on the use of cavitation and Fenton chemistry at pilot scale
      operation and tries to establish the missing design related information for large
      scale operation of wastewater treatment.

PMID- 19758753
TI  - Determination of Pb2+ ions by a modified carbon paste electrode based on multi
      walled carbon nanotubes (MWCNTs) and nanosilica.
AB  - A novel carbon paste ion selective electrode for determination of trace amount of
      lead was prepared. Multi-walled carbon nanotubes (MWCNTs) and nanosilica were
      used for improvement of a lead carbon paste sensor response. MWCNTs have a good
      conductivity which helps the transduction of the signal in carbon paste
      electrode. The electrode composition of 20 wt% paraffin oil, 57% graphite powder,
      15% ionophore (thiram), 5% MWCNTs, and 3% nanosilica showed the stable potential
      response to Pb(2+) ions with the Nernstian slope of 29.8 (+/-0.2)mV decade(-1)
      over a wide linear concentration range of 10(-7)-10(-2)mol L(-1). The electrode
      has fast response time, and long term stability (more than 2 months). The
      proposed electrode was used to determine the concentration of lead ions in waste
      water and black tea samples.

PMID- 19758754
TI  - Recovery of high surface area mesoporous silica from waste hexafluorosilicic acid
      (H2SiF6) of fertilizer industry.
AB  - In this article we report recovery of mesoporous silica from the waste material
      (hexafluorosilicic acid) of phosphate fertilizer industry. The process involves
      the reaction of hexafluorosilicic acid (50 ml, 24 wt% H(2)SiF(6)) and 100ml,
      0.297 M Na(2)CO(3) to generate the alkaline aqueous slurry. Silica was separated
      from the slurry by filtration and the sodium fluoride was extracted from the
      aqueous solution by evaporation method. The obtained mesoporous silica was
      characterized by N(2) absorption/desorption (BET), thermogravimetric analysis
      (TGA), X-ray diffraction (XRD), scanning electron microscope (SEM), and EDS. The
      results confirm that the separation of silica and NaF was successful and the
      final products have high purity. The silica product was found to have an average
      pore diameter of 4.14 nm and a high surface area (up to 800 m(2)/g). The process
      reported in this study may significantly reduce the release of hazardous
      materials into the environment and it might confer economic benefits to the
      responsible industries.

PMID- 19758755
TI  - Development of a coprecipitation system for the speciation/preconcentration of
      chromium in tap waters.
AB  - A method for the speciation of chromium(III), chromium(VI) and determination of
      total chromium based on coprecipitation of chromium(III) with dysprosium
      hydroxide has been investigated and applied to tap water samples. Chromium(III)
      was quantitatively recovered by the presented method, while the recovery values
      for chromium(VI) was below 10%. The influences of analytical parameters including
      amount of dysprosium(III), pH, centrifugation speed and sample volume for the
      quantitative precipitation were examined. No interferic effects were observed
      from alkali, earth alkali and some transition metals for the analyte ions. The
      detection limits (k=3, N=15) were 0.65 microg/L for chromium(III) and 0.78
      microg/L for chromium(VI). The validation of the presented method was checked by
      the analysis of certified reference materials.

PMID- 19758756
TI  - Understanding the mechanisms of cold-evoked pain in humans.

PMID- 19758757
TI  - Comparison of the efficiency of five suction light traps under field conditions
      in South Africa for the collection of Culicoides species.
AB  - Culicoides biting midges (Diptera: Ceratopogonidae) are involved in the
      transmission of a variety of pathogens, the economically most important being the
      orbiviruses that cause bluetongue and African horse sickness; both of which have
      been shown to be multi-vector diseases. The identification of all potential
      vectors will be crucial for the implementation of integrated control measures and
      disease risk analysis. The primary monitoring tools used for the collection of
      Culicoides midges are various models of suction light traps. In order to
      facilitate comparison of data between laboratories the efficiency of five traps
      (Onderstepoort, Rieb, mini-CDC, Pirbright, BG-sentinel), used at present and in
      the past in Europe, was compared in the field in South Africa. Comparisons were
      done either in three replicates of a 4x4 or two replicates of a 5x5 randomized
      Latin square design. The Onderstepoort trap collected significantly more
      Culicoides midges than the other traps. Relatively small but statistically
      significant differences were found in the species composition, parous rates, sex
      ratios as well as the ratio of Culicoides midges to other insects, as determined
      by the different traps. It will be important to determine the significance and
      underlying causes for these differences.

PMID- 19758758
TI  - V-ATPase inhibitors and implication in cancer treatment.
AB  - Acidity is one of the main features of the tumors. The V-ATPase is the primary
      responsible for the control of tumor microenvironment by proton extrusion to the
      extracellular medium. The acid environment favors tissue damage, activation of
      destructive enzymes in the extracellular matrix, the acquisition of metastatic
      cell phenotypes as well as increasing the destructive capacity. The application
      of specific inhibitors of V-ATPases, can decrease the acidity of tumor and may
      allow the reduction of tumor metastasis, acting on the survival of tumor cells
      and prevent the phenomena of chemoresistance. Among the most important inhibitors
      can be distinguished benzolactone enamides (salicylihalamide), lobatamide A and
      B, apicularen, indolyls, oximidine, macrolactone archazolid, lobatamide C, and
      cruentaren. The latest generation of inhibitors includes NiK12192, FR202126, and
      PPI SB 242784. The purpose of this paper is to describe the latest advances in
      the field of V-ATPase inhibitors, describe further developments related to the
      classic inhibitors, and discuss new potential applications of these drugs in
      cancer treatment.

PMID- 19758759
TI  - The role of topoisomerase IIalpha and HER-2 in predicting sensitivity to
      anthracyclines in breast cancer patients.
AB  - Human epidermal growth factor receptor-2 (HER-2) and topoisomerase IIalpha (topo
      IIalpha) co-inhabit chromosome 17. In the search for predictive biomarkers to
      refine clinical prescription of cytotoxic agents, both HER-2 and topo IIalpha are
      under exploration for their potential role in identifying individuals with early
      breast cancer who may benefit from anthracycline therapy. Whilst recent meta
      analyses support a predictive role for HER-2 amplification, it remains unclear
      whether HER-2 is the critical biomarker or whether it is a surrogate marker for
      topo IIalpha alteration, a known drug target of anthracyclines. The major
      limitation in considering HER-2 as a single marker is heterogeneity within the
      subgroups of HER-2 positive and HER-2 negative disease. For topo IIalpha, current
      data is inconclusive. Issues plaguing this field are technical variability in
      marker definition, complex regulation pathway of topo IIalpha and lack of
      prospective, adequately powered studies. With current evidence, neither HER-2 nor
      topo IIalpha gene status can be considered clinically valuable markers for
      anthracycline benefit. This paper will focus on issues relating to reliable
      detection and predictive analyses of HER-2 and topo IIalpha, and highlight
      potential developments in improving individualized approach to anthracycline use
      in early breast cancer patients.

PMID- 19758760
TI  - Second-line therapy for advanced pancreatic cancer: a review of the literature
      and future directions.
AB  - Whereas first-line chemotherapy (CT) with single-agent gemcitabine or gemcitabine
      based combinations provides a proven benefit in patients with locally advanced or
      metastatic pancreatic cancer (PC), the role of salvage CT after gemcitabine
      failure is not well-established and to date no regimen has emerged as preferred
      in this setting. Several clinical trials have investigated the efficacy and
      toxicity-profile of second-line CT and indicated that selected patients may
      obtain significant benefit from it, also with regard to survival. However,
      definitive results from large randomized phase III studies are still lacking, and
      the evidence for clinical benefit of salvage CT is based on small phase II trials
      that evaluated different treatment schedules in heterogeneous populations. The
      main goal of this paper is reviewing this topic.

PMID- 19758761
TI  - Neurosteroids: endogenous allosteric modulators of GABA(A) receptors.
AB  - In the mammalian central nervous system activation of the ionotropic GABA(A)
      receptor by the neurotransmitter GABA plays a crucial role in controlling
      neuronal excitability. This essential form of neuronal regulation may be subject
      to "fine tuning" by particular metabolites of progesterone and
      deoxycorticosterone, which bind directly to the GABA(A) receptor to enhance the
      actions of GABA. Originally such steroids were considered to act as endocrine
      messengers, being synthesised in peripheral glands such as the adrenals and
      ovaries and crossing the blood brain barrier to influence neuronal signalling.
      However, it is now evident that certain neurons and glia may produce such
      "neurosteroids" and that these locally synthesised modulators may act in a
      paracrine, or indeed an autocrine manner to influence neuronal activity.
      Neurosteroid synthesis may change dynamically in a variety of physiological
      situations (e.g. stress, pregnancy) and perturbations in their levels are
      implicated in a variety of neurological and psychiatric disorders. Here we will
      consider (1) evidence supporting the concept that neurosteroids act as local
      regulators of neuronal inhibition, (2) that extrasynaptic GABA(A) receptors
      appear to be a particularly important neurosteroid target and (3) recent advances
      in defining the neurosteroid binding site(s) on the GABA(A) receptor.

PMID- 19758762
TI  - Neural mechanisms underlying changes in stress-sensitivity across the menstrual
      cycle.
AB  - Hormonal fluctuations across the menstrual cycle are thought to play a central
      role in premenstrual mood symptoms. In agreement, fluctuations in gonadal hormone
      levels affect brain processes in regions involved in emotion regulation. Recent
      findings, however, implicate psychological stress as a potential mediating factor
      and thus, we investigated whether effects of moderate psychological stress on
      relevant brain regions interact with menstrual cycle phase. Twenty-eight healthy
      women were tested in a crossover design with menstrual cycle phase (late luteal
      versus late follicular) and stress (stress induction versus control) as within
      subject factors. After stress induction (or control), we probed neural responses
      to facial expressions using fMRI. During the late luteal phase, negative affect
      was highest and the stress-induced increase in heart rate was mildly augmented.
      fMRI data of the control condition replicate previous findings of elevated
      amygdala and medial prefrontal cortex responses when comparing the late luteal
      with the late follicular phase. Importantly, stress induction had opposite
      effects in the two cycle phases, with unexpected lower response magnitudes in the
      late luteal phase. Moreover, the larger the increase in allopregnanolone
      concentration across the menstrual cycle was, the smaller the amygdala and medial
      prefrontal cortex responses were after stress induction in the late luteal phase.
      Our findings show that moderate psychological stress influences menstrual cycle
      effects on activity in the emotion regulation circuitry. These results provide
      potential insights into how fluctuations in allopregnanolone that naturally occur
      during the menstrual cycle may change stress vulnerability.

PMID- 19758763
TI  - Cognitive modulation of endocrine responses to CRH stimulation in healthy
      subjects.
AB  - BACKGROUND: The hypothalamic-pituitary adrenal (HPA) axis is critical for
      biobehavioral adaptation to challenge and appears dysregulated in a range of
      psychiatric disorders. Its precise role in psychopathology remains unclear and
      discrepant and difficult to explain findings abound in the clinical literature.
      Basic research suggests this system is sensitive to psychosocial cues, but
      psychosocial milieu factors are rarely controlled or examined in psychiatric
      studies using biological probes of the HPA axis. To test the hypothesis that
      psychological factors might complicate HPA study results even in direct,
      pharmacological challenge paradigms, endocrine responses to corticotropin
      releasing hormone (CRH) were examined under two different cognitive preparation
      conditions. METHODS: Healthy subjects (n=32) received standard instructions or a
      cognitive intervention (CI) prior to injection with CRH and placebo, given on
      separate days in random order. The CI combined access to control over drug
      exposure with novelty reduction and coping enhancement. Blood samples were
      obtained via intravenous catheter before and after CRH. RESULTS: Cognitive
      intervention reduced corticotropin (ACTH) levels, but only when CRH was given
      first (intervention by order interaction). It did not reduce cortisol response.
      The CI and visit (1st or 2nd) both impacted cortisol levels on placebo day.
      CONCLUSIONS: Modifiable psychological factors may amplify or inhibit HPA axis
      activity in pharmacological activation paradigms, including CRH stimulation
      tests. The factors manipulated by the CI (novelty/familiarity, control and
      coping) may have particular salience to the HPA axis. Differential sensitivity to
      such factors could impact results in studies applying biological HPA probes to
      psychiatric populations.

PMID- 19758764
TI  - Local lipopolysaccharide injection: a potential novel treatment for heterotopic
      ossification.
AB  - Heterotopic ossification (HO) is a frequent complication after musculoskeletal
      trauma and surgical procedures. It usually decreases joint mobility and
      eventually causes loss of joint function. However, there is no satisfied
      treatment available for HO. Lipopolysaccharide (LPS) is traditionally recognized
      as an endotoxin. Recently, studies found LPS was associated with loss of bone
      during bacterial infection and periprosthetic osteolysis after total joint
      replacement. Cell and molecular biology studies further found that LPS initiated
      the osteoclast formation, stimulated osteoclast activity and inhibited osteoblast
      differentiation. Given HO is an abnormality in bone modeling which increases bone
      mass within extraskeletal soft tissues, we herein hypothesize that local LPS
      injection might be a potential novel treatment for HO.

PMID- 19758765
TI  - Platelet dysfunction can be the hidden risk factor for death in new influenza A
      (H1N1).

PMID- 19758766
TI  - Detection of lung cancer by oral examination.
AB  - Lung cancer continues to be the leading cause of cancer deaths worldwide.
      Cigarette smoking is the predominant cause of lung cancer. Researchers found that
      tobacco-induced molecular changes in the oral epithelium are similar to those in
      the lung epithelium. Furthermore, there has been considerable progress in
      investigating the tumorigenesis of oral epithelium using molecular markers. These
      results offer hope that we can predict lung cancer in smokers by oral
      examination, which is much easier and more practical than lung biopsy. The
      hypothesis is to collect oral epithelial cells by gently scraping the oral
      mucosa, and analyze the DNA variation in these cells using molecular biological
      methods. Therefore, the oral epithelium is serving as a surrogate tissue for
      assessing smoking-induced molecular damage to the lungs and thus have important
      implications for early detection of lung cancer.

PMID- 19758767
TI  - Duct obstruction: the possible etiopathogenesis of benign prostatic hyperplasia.
AB  - Benign prostatic hyperplasia (BPH) is a common disease of the aged. And its
      etiopathogenesis is still uncertain after centuries' research. Ducts of prostate
      were often found obstructed and ectasy in pathological examinations. Recent
      studies suggest that pressure can facilitate the proliferation of prostatic
      cells. Therefore we hypothesize that ductal obstruction can induce augmentation
      of intraductal pressure and facilitate the proliferation of prostatic cells.
      Ductal obstruction might play a role in the etiopathogenesis of BPH. If our
      hypothesis can be further supported by future researches, it may change the
      present etiopathogenesis theory of BPH as well as the treatment strategies of it.

PMID- 19758768
TI  - About strawberry, crab claws, and the Sir James Black's invention. Hypothesis:
      can we battle keloids with propranolol?
AB  - The cutaneous hemangiomas of infancy or infantile hemangiomas are the most common
      benign tumor of childhood. They were formerly known as strawberry hemangiomas in
      reason of its typical appearance although uncommon morphologic variations can be
      found. Usually hemangiomas are harmless growths that are the result of
      proliferation of endothelial cells during early childhood. Involution of the
      lesion occurs at 12-18 months and can last up to 7 years. Occasionally, infantile
      hemangiomas suffer dramatic overgrowth causing esthetical damages, as well
      compromises to vital structures that requires prompt intervention. Propranolol, a
      beta-adrenergic receptor antagonist that was invented by Sir James Black in
      1960s, appears to be an effective treatment for infantile hemangiomas and should
      now be used as a first-line treatment in hemangiomas when intervention is
      required. Keloids (that resembles crab claws) and hypertrophic scars are fibrous
      tissue outgrowths that result from a derailment in the normal wound-healing
      process. Systemic or intralesional propranolol may play a role in the
      amelioration of keloids and hypertrophic scars due to their potential to induce
      vasoconstriction of over proliferating tissues, triggering apoptosis of
      endothelial cells and also to their effect as modulator of inflammatory process
      during wound healing. In adding the propranolol to the melting pot of abnormal
      (or supra-normal) wound healing, we hypothesized that we can battle keloids with
      propranolol.

PMID- 19758769
TI  - Is gallium nitrate an effective kidney stone, calcified uterine fibroid,
      atherosclerosis and cataract anti-nanobacteria treatment? A case history and
      hypothesis.

PMID- 19758770
TI  - Patterns of illegal drug use among an adult alcohol dependent population: results
      from the National Survey on Drug Use and Health.
AB  - The use of illegal drugs is common in alcohol dependence and significant
      psychological and social consequences are associated with the concurrent use of
      alcohol and illegal drugs. However, little literature has examined the patterns
      of concurrent-drug use in alcohol dependent individuals. A latent class analysis
      (LCA) was used to determine whether patterns of past year illegal drug use
      existed in a national sample of 6059 alcohol dependent respondents of the
      combined 2005, 2006 and 2007 National Survey on Drug Use and Health. Multinomial
      logistic regression was then used to determine whether demographic variables,
      mental health disturbance and social consequences were predictive of drug use
      classes. Results of the LCA demonstrated a 5-class solution with optimal fit
      deduced by Bayesian Information Criterion minima. The five classes included: a
      close to zero probability of illegal drug use (class 1: 65%), medium marijuana,
      medium sedatives/tranquilizers and high analgesics (class 2: 7%), high marijuana,
      medium cocaine use (class 3: 21%), high probabilities of marijuana, cocaine,
      sedatives and analgesic use (class 4: 6%) and a high concurrent-drug use except
      other hallucinogens (class 5: 1%). Regression results suggest that younger age,
      comorbidity, engaging in deviant behaviors, sexually transmitted infection and
      incarceration are associated with concurrent illegal drug use in alcohol
      dependent individuals. Findings advocate that more intense psychiatric and drug
      dependence treatment resources may be needed for concurrent-drug using alcohol
      dependent populations and provide evidence for targeted prevention and treatment
      interventions.

PMID- 19758771
TI  - Smoking and drinking among college students: "it's a package deal".
AB  - BACKGROUND: This paper reports on qualitative research on smoking in contexts
      associated with drinking among college students. Although a plethora of survey
      research has shown a positive association between smoking and alcohol use, little
      attention has been given to the utility functions of these co-occurring
      behaviors. METHODS: Data are drawn from semi-structured interviews with college
      freshmen at a large Mid-western university in the U.S. (n=35). In addition,
      eleven focus groups with fraternity and sorority members were conducted (n=70).
      Interviews and focus groups focused on a range of issues including current
      smoking behavior, reasons for smoking, and smoking and drinking. RESULTS: A
      review of qualitative responses reveals that smoking served multiple utility
      functions for this population including (1) facilitating social interaction
      across gender, (2) allowing one to structure time and space at a party, (3)
      enabling "party" smokers to smoke with fewer negative side effects, and (4)
      helping to calm one down when drunk. CONCLUSIONS: Whereas smoking was stigmatized
      during the context of one's everyday life as a student, at parties while
      consuming alcohol, smoking was viewed as normative and socially acceptable.
      Preventive interventions are needed on college campus that target co-substance
      use and address widespread misperceptions about the harm of tobacco use and
      addiction.

PMID- 19758772
TI  - Seasonal variation in detection of bacterial DNA in arthritic stifle joints of
      dogs with cranial cruciate ligament rupture using PCR amplification of the 16S
      rRNA gene.
AB  - An underappreciated cause and effect relationship between environmental bacteria
      and arthritis may exist. Previously, we found that stifle arthritis in dogs was
      associated with the presence of environmental bacteria within synovium. Cranial
      cruciate ligament rupture (CCLR) is often associated with stifle arthritis in
      dogs. We now wished to determine whether seasonal variation in detection of
      bacterial material may exist in affected dogs, and to also conduct analyses of
      both synovium and synovial fluid. We also wished to analyze a larger clone
      library of the 16S rRNA gene to further understanding of the microbial population
      in the canine stifle. Synovial biopsies were obtained from 117 affected dogs from
      January to December 2006. Using PCR, synovium and synovial fluid were tested for
      Borrelia burgdorferi and Stenotrophomonas maltophilia DNA. Broad-ranging 16S rRNA
      primers were also used and PCR products were cloned and sequenced for bacterial
      identification. Overall, 41% of arthritic canine stifle joints contained
      bacterial DNA. Detection of bacterial DNA in synovial fluid samples was
      increased, when compared with synovium (p<0.01). Detection rates were highest in
      the winter and spring and lowest in the summer period, suggesting environmental
      factors influence the risk of translocation to the stifle. Organisms detected
      were predominately Gram's negative Proteobacteria, particularly the orders
      Rhizobiales (32.8% of clones) and Burkholderiales (20.0% of clones), usually as
      part of a polymicrobial population. PCR-positivity was inversely correlated with
      severity of arthritis assessed radiographically and with dog age. Bacterial
      translocation to the canine stifle may be associated with changes to the indoor
      environment.

PMID- 19758773
TI  - Prenatal presentation and postnatal management of congenital thoracic
      malformations.
AB  - The antenatal finding of a congenital thoracic malformation (CTM) leads to
      anxiety in the parents and uncertainty as to the optimal management. The
      antenatal spectrum of CTM includes congenital cystic adenomatoid malformation,
      sequestration, congenital lobar emphysema, enteric and bronchogenic cysts, and
      bronchial atresia. Most lesions require no antenatal intervention, and shrink
      substantially in the third trimester, but if fetal hydrops develops, then
      antenatal intervention is required, occasionally medical but more usually
      surgical, because mortality is high. If the baby is symptomatic in the newborn
      period, then some form of surgical intervention is clearly required. The
      asymptomatic baby presents a therapeutic dilemma. Advocates of early surgery
      point to the complications of CTM, which include infection, pneumothorax,
      bleeding and malignant transformation. Those who are proponents of conservative
      management retort that some CTM disappear postnatally, and that the complication
      rate is unknown; many children appear never to need surgery. Furthermore, there
      is clearcut evidence that excision of a CTM does not totally eliminate the risk
      of a subsequent malignancy. It is clear that, both antenatally and postnatally,
      counselling of the family on a case by case basis is needed. The limitations of
      present evidence should be stressed. Different families will make different
      decisions about postnatal surgery in an asymptomatic baby. If surgery is
      performed, morbidity is low, particularly with a video-assisted thoracoscopic
      (VATS) procedure.

PMID- 19758774
TI  - Cholesterol addition protects membrane intactness during cryopreservation of
      stallion sperm.
AB  - Addition of cholesterol to sperm membranes improved equine sperm stability during
      semen cryopreservation; however, it also reduced in vivo fertility. The objective
      of the present study was to determine the effects of adding cholesterol to
      stallion sperm prior to freezing, and subsequently removing it from frozen-thawed
      sperm. Semen from 12 stallions was subjected to four treatments: (T1) control,
      semen was diluted with Kenney extender, centrifuged, and resuspended to 100 x
      10(6)spermatozoa/mL in INRA 82 freezing extender, packaged into 0.5-mL straws,
      cooled to 5 degrees C, and cryopreserved in liquid nitrogen; (T2) T1 with the
      addition of cholesterol before cooling (the cholesterol was incorporated to the
      sperm membranes with the methyl-beta-cyclodextrin-cholesterol complex); (T3) T2
      with post-thaw removal of the cholesterol with 0.052 mg methyl-beta
      cyclodextrin/50 x 10(6) sperm; and (T4) T3 with 0.156 mg methyl-beta
      cyclodextrin/50 x 10(6) sperm. Sperm progressive motility and functional
      integrity of sperm plasma membranes were evaluated microscopically and by the
      hyposmotic swelling test, respectively. Using flow cytometry, physical integrity
      of sperm plasma membranes was assessed with propidium iodide, acrosomal integrity
      with fluoresceinated lectin peanut agglutinin, and rate of sperm acrosome
      reaction induced with of the calcium ionophore A23187. Cholesterol inclusion (T2)
      increased the proportion of frozen-thawed sperm with intact plasma membrane.
      Nevertheless, sperm from T2 (9.3+/-5.9%) had a lower rate of acrosome reaction
      after induction, compared to the control group (16.5+/-11.0%). After cholesterol
      removal, there was no increase in the induced acrosome reaction rate (T3: 11.3+/
      7.1% and T4: 11.8+/-9.9%). Perhaps the cyclodextrin concentrations used were too
      low to remove sufficient cholesterol from sperm membranes to restore the ability
      of cryopreserved sperm to undergo an acrosome reaction. Regardless, the addition
      of cholesterol to improve post-thaw sperm integrity, and its subsequent removal,
      still has potential for cryopreservation of stallion sperm.

PMID- 19758775
TI  - [Diagnosis of dyschezia].
AB  - Outlet constipation is a frustrating condition for both patients and clinicians.
      The former are reluctant to evoke this disabling condition. For the latter,
      decision-making remains uncertain since non-specific strategies are unhelpful
      (constipation). Thus, careful symptomatic assessment (stool consistencies),
      dynamic examination of the anorectal area (anismus, rectocele) and balloon
      expulsion test may plan therapeutic options in current situations.

PMID- 19758776
TI  - [Role of chromoendoscopy for the management of colorectal neoplasia].
AB  - Early detection of colorectal neoplasia is a major aim for gastroenterologists,
      much more than diagnosing advanced cancer. Chromoscopy using mostly indigo
      carmine dye at 0.2% is an important tool in this setting, with proven interest
      for the detection of flat neoplasia in specific at risk patients including Lynch
      syndrome and inflammatory bowel disease. No other diagnostic tool has
      demonstrated its superiority, or even its equivalence, to chromoscopy in these
      situations. With less scientific evidences, chromoscopy helps the endoscopist to
      delimitate neoplasia before and after endoscopic treatment, and in the specific
      situation of digestive polyposes. In contrast, there is no proven interest of
      systematic chromoscopy in the usual situation of coloscopy for cancer screening
      in moderate or high-risk patients. However, a frequent use of chromoscopy is
      probably associated with higher ability of the endoscopist, even in usual
      colonoscopy indications, to identify difficult colorectal lesions.

PMID- 19758777
TI  - [Diagnosis and follow-up of small intraductal papillary mucinous neoplasm of the
      pancreas].
AB  - Intraductal papillary mucinous tumours are diagnosed more and more often
      fortuitously. Initial work-up relies on CT scan, CP-MRI and endoscopic ultrasound
      of excellent technical quality. Their aspect might be extremely proteiform. They
      usually appear as cystic lesion, unique or multiple, localized or diffuse,
      involving main or branch pancreatic duct. The communication between the cystic
      lesion and the ductal system is essential for diagnosis. If main pancreatic duct
      is not involved and in absence of mural nodules, it is recommended not to resect
      them and to initiate follow-up. The follow-up examination relies on CP-MRI and,
      in case of symptomatic or imaging modifications, on endoscopic ultrasound. The
      interval between follow-up examinations remains to be determined. In case of
      imaging change might lead to resection.

PMID- 19758778
TI  - [Unexplained dysphagia in a young adult: management modalities].
AB  - Oropharyngeal dysphagia is very rare in young adults. Thoracic dysphagia work-up
      must include upper GI endoscopy and esophageal biopsies, to exclude eosinophilic
      esophagitis, which requires specific treatment with corticosteroids and
      endoscopic dilations. Esophageal manometry and barium swallow must be performed
      if upper GI endoscopy and biopsies are negative. High-resolution esophageal
      manometry, by disclosing a true functional imaging of swallow, appears as a real
      breakthrough for the diagnosis of dysphagia occurring after antireflux and
      bariatric surgery.

PMID- 19758779
TI  - Second- and third-line chemotherapy in patients with metastatic pancreatic
      adenocarcinoma: feasibility and potential benefits in a retrospective series of
      117 patients.
AB  - BACKGROUND: Chemotherapy is effective in metastatic pancreatic adenocarcinoma
      (PAC), but the benefits of second- and third-line chemotherapy remain unclear.
      METHODS: We studied all patients followed consecutively for metastatic PAC, and
      registered at our institution between 1997 and 2006. We retrospectively analyzed
      the following data in terms of chemotherapy: tumor response; time to tumor
      progression (TTP) for each line; and overall survival (OS). Efficacy of second
      line regimens was assessed using the growth modulation index (GMI). RESULTS: Out
      of 117 patients, 99 (85%) received at least one line of chemotherapy, 53 (45%)
      received two lines and 24 (21%) had three or more lines. Median OS was 6.7 months
      for all 117 patients, 1.8 months for 18 patients who never received chemotherapy,
      4.6 months for 46 patients who received one-line chemotherapy and 11.5 months for
      53 patients who received at least two lines. Median OS from the beginning of the
      second-line was 4.7 months. The GMI demonstrated beneficial effects of second
      line treatment on disease progression, with a GMI greater than 1.33 in 57%
      (30/53) of patients. CONCLUSION: More than half the patients with metastatic PAC
      progression while receiving one-line chemotherapy achieved better disease control
      on receiving two lines of treatment.

PMID- 19758780
TI  - Investigation of the HPLC response of NSAIDs by fractional experimental design
      and multivariate regression analysis. Response optimization and new retention
      parameters.
AB  - The optimization of the HPLC procedures and the investigation of the predictive
      models are generally seen as distinct tasks although they could be both
      approached by very similar chemometric methods. In this work we used chemometric
      approaches to both optimize the separation of a non-steroidal anti-inflammatory
      drugs (NSAIDs) set by isocratic reversed-phase HPLC and start-up the development
      of retention predictive models. The screening of responsive variables and the
      search for an optimal experimental domain provided also an insight into the
      structure-chromatographic response relationships for the considered compounds
      which were particularly helpful to derive new retention parameters.

PMID- 19758781
TI  - Quantitative determination of residual active pharmaceutical ingredients and
      intermediates on equipment surfaces by ion mobility spectrometry.
AB  - Ion mobility spectrometry (IMS) is an analytical technique that separates ions
      based on their gas phase mobility at atmospheric pressure. Since gas phase ion
      mobility is a function of the shape and structure of the ion, this technique has
      the potential to provide unique specificity and selectivity. Furthermore, IMS is
      very sensitive (subnanogram detection limits for many small molecules), and a
      single analysis is typically completed within 1 min. In principle, these features
      of IMS should make it an ideal choice for use in cleaning verification analysis
      of pharmaceutical manufacturing equipment. This report describes the successful
      development and validation of three different equipment cleaning verification
      methods using IMS. The methods were developed for a specific intermediate
      (Compound A) in the synthetic route for a drug substance as well as for final
      drug substances (active pharmaceutical ingredients Compounds B and C). The
      cleaning verification methods were validated with respect to specificity,
      linearity, precision, accuracy, stability, and limit-of-quantitation. In all
      cases, the limits-of-quantitation were determined to be at the nanogram or sub
      nanogram level. Both swab and rinse samples collected from the equipment surfaces
      were successfully analyzed and manufacturing equipment down-time was
      significantly minimized due to the reduction in cleaning verification analysis
      time (for example, the total analysis time for more than 30 samples using IMS was
      reduced to less than 2h).

PMID- 19758782
TI  - Practical comparison of 2.7 microm fused-core silica particles and porous sub-2
      microm particles for fast separations in pharmaceutical process development.
AB  - Fused-core silica stationary phases represent a key technological advancement in
      the arena of fast HPLC separations. These phases are made by fusing a 0.5 microm
      porous silica layer onto 1.7 microm nonporous silica cores. The reduced intra
      particle flow path of the fused particles provides superior mass transfer
      kinetics and better performance at high mobile phase velocities, while the fused
      core particles provide lower pressure than sub-2 microm particles. In this work,
      chromatographic performance of the fused-core particles (Ascentis Express) was
      investigated and compared to that of sub-2 microm porous particles (1.8 microm
      Zorbax Eclipse Plus C18 and 1.7 microm Acquity BEH C18). Specifically, retention,
      selectivity, and loading capacity were systematically compared for these two
      types of columns. Other chromatographic parameters such as efficiency and
      pressure drop were also studied. Although the fused-core column was found to
      provide better analyte shape selectivity, both columns had similar hydrophobic,
      hydrogen bonding, total ion-exchange, and acidic ion-exchange selectivities. As
      expected, the retention factors and sample loading capacity on the fused-core
      particle column were slightly lower than those for the sub-2 microm particle
      column. However, the most dramatic observation was that similar efficiency
      separations to the sub-2 microm particles could be achieved using the fused-core
      particles, without the expense of high column back pressure. The low pressure of
      the fused-core column allows fast separations to be performed routinely on a
      conventional LC system without significant loss in efficiency or resolution.
      Applications to the HPLC impurity profiling of drug substance candidates were
      performed using both types of columns to validate this last point.

PMID- 19758783
TI  - Proline-rich polypeptide complex (PRP) regulates secretion of inflammatory
      mediators by its effect on NF-kappaB activity.
AB  - A proline-rich polypeptide complex (PRP) with immunoregulatory and procognitive
      activities shows beneficial effects in the Alzheimer's disease (AD). The
      mechanism of action of PRP is not yet fully clarified, we have shown that the PRP
      complex inhibits overproduction of reactive oxygen species, nitric oxide and
      proinflammatory cytokines induced by lipopolysaccharide (LPS). LPS stimulation
      exerts its inflammatory effects through the activation of the classical nuclear
      factor-kappaB (NF-kappaB) pathway. The results presented in this study showed the
      ability of PRP to inhibit the NF-kappaB activity induced by LPS while it
      increased activity of NF-kappaB in untreated cells. Examining the effect of PRP
      on IkappaB it was shown that relative level of IkappaB was lowered in the
      presence of PRP. It seems that in cells untreated with LPS, PRP can activate
      proteasome system and stimulate IkappaB degradation. Our results suggest that the
      regulatory effect of PRP on inflammatory processes may be associated with the
      influence of PRP on NF-kappaB translocation. Inhibitory effect of PRP on NF
      kappaB activity might, at least in part, contribute to the beneficial therapeutic
      effects in the case of Alzheimer's disease.

PMID- 19758784
TI  - Clustering: a neural network approach.
AB  - Clustering is a fundamental data analysis method. It is widely used for pattern
      recognition, feature extraction, vector quantization (VQ), image segmentation,
      function approximation, and data mining. As an unsupervised classification
      technique, clustering identifies some inherent structures present in a set of
      objects based on a similarity measure. Clustering methods can be based on
      statistical model identification (McLachlan & Basford, 1988) or competitive
      learning. In this paper, we give a comprehensive overview of competitive learning
      based clustering methods. Importance is attached to a number of competitive
      learning based clustering neural networks such as the self-organizing map (SOM),
      the learning vector quantization (LVQ), the neural gas, and the ART model, and
      clustering algorithms such as the C-means, mountain/subtractive clustering, and
      fuzzy C-means (FCM) algorithms. Associated topics such as the under-utilization
      problem, fuzzy clustering, robust clustering, clustering based on non-Euclidean
      distance measures, supervised clustering, hierarchical clustering as well as
      cluster validity are also described. Two examples are given to demonstrate the
      use of the clustering methods.

PMID- 19758785
TI  - A discrimination method for the detection of pneumonia using chest radiograph.
AB  - This paper presents a statistical method for the detection of lobar pneumonia
      when using digitized chest X-ray films. Each region of interest was represented
      by a vector of wavelet texture measures which is then multiplied by the
      orthogonal matrix Q(2). The first two elements of the transformed vectors were
      shown to have a bivariate normal distribution. Misclassification probabilities
      were estimated using probability ellipsoids and discriminant functions. The
      result of this study recommends the detection of pneumonia by constructing
      probability ellipsoids or discriminant function using maximum energy and maximum
      column sum energy texture measures where misclassification probabilities were
      less than 0.15.

PMID- 19758786
TI  - Motion compensated iterative reconstruction of a region of interest in cardiac
      cone-beam CT.
AB  - A method for motion compensated iterative CT reconstruction of a cardiac region
      of-interest is presented. The algorithm is an ordered subset maximum likelihood
      approach with spherically symmetric basis functions, and it uses an ECG for
      gating. Since the straightforward application of iterative methods to CT data has
      the drawback that a field-of-view has to be reconstructed, which covers the
      complete volume contributing to the absorption, region-of-interest reconstruction
      is applied here. Despite gating, residual object motion within the reconstructed
      gating window leads to motion blurring in the reconstructed image. To limit this
      effect, motion compensation is applied. Hereto, a gated 4D reconstruction at
      multiple phases is generated for the region-of-interest, and a limited set of
      vascular landmarks are manually annotated throughout the cardiac phases. A dense
      motion vector field is obtained from these landmarks by scattered data
      interpolation. The method is applied to two clinical data sets at strongest
      motion phases. Comparing the method to standard gated iterative reconstruction
      results shows that motion compensation strongly improved reconstruction quality.

PMID- 19758787
TI  - Inhibitory IgG Fc receptor promoter region polymorphism is a key genetic element
      for murine systemic lupus erythematosus.
AB  - The autoimmune-type Fcgr2b with deletion polymorphism in AP-4-binding site in the
      promoter region is suggested to be one most plausible susceptibility gene for
      systemic lupus erythematosus (SLE). We previously found that there is a strong
      epistatic interaction between the autoimmune-type Fcgr2b polymorphism and Y
      chromosome-linked autoimmune acceleration (Yaa) mutation, thus severe SLE
      observed in BXSB males neither develops in BXSB females nor in the congenic
      BXSB.IIB(B6) males carrying wild C57BL/6-type Fcgr2b. Present studies examined
      whether the wild-type Fcgr2b could suppress SLE in mice carrying Yaa-unrelated
      SLE susceptibility genes. Comparison of disease features between SLE-prone (NZW x
      BXSB) F1 females and the congenic (NZW x BXSB.IIB(B6)) F1 females carrying wild
      type Fcgr2b showed that, as compared with findings in the former, SLE features
      including activation/proliferation of not only B cells but also T cells and
      monocytes/macrophages were all inhibited in the latter. It was concluded that the
      autoimmune-type Fcgr2b promotes and the wild-type inhibits SLE through mechanisms
      that promote and suppress activation/proliferation of a wide variety of immune
      cells, respectively. Thus, the Fcgr2b polymorphism is a key genetic element for
      not only Yaa-related but also Yaa-unrelated lupus.

PMID- 19758788
TI  - Unconditioned adult-derived neurosphere cells mainly differentiate towards
      astrocytes upon transplantation in sclerotic rat hippocampus.
AB  - PURPOSE: Cell transplantation is being investigated as an alternative treatment
      for medically refractory temporal lobe epilepsy (TLE). In this study the fate of
      adult-derived neurosphere cells was evaluated after transplantation in the
      lesioned hippocampus of the intrahippocampal kainic acid (KA) model for TLE.
      METHODS: Neurosphere-forming cells were derived from the subventricular zone
      (SVZ) of transgenic green fluorescent protein (GFP) reporter mice and expanded in
      culture. After 10 passages in vitro neurosphere-derived cells were transplanted
      in the hippocampus three days (KA3d group) and three weeks (KA3w group) after
      intrahippocampal KA injection. Survival and differentiation of neurosphere cells
      were evaluated three and six weeks after transplantation. RESULTS: A fraction
      (about 1%) of GFP-expressing neurosphere cells survived for at least six weeks
      after transplantation with a higher and more robust survival rate in the KA3d
      compared to the KA3w group. Although a small fraction of the cells expressed the
      neuronal marker NeuN, neurosphere cells mainly differentiated towards astrocytes.
      DISCUSSION: Our results indicate that adult-derived neurosphere cells are able to
      survive upon transplantation in the sclerotic hippocampus. The transplanted cells
      do not or hardly contribute to neuronal replacement and mainly adopt an
      astrogliotic fate.

PMID- 19758789
TI  - HTR2A gene variation is involved in antidepressant treatment response.
AB  - Two serotonin 2A receptor (HTR2A) SNPs recently reported to be associated with
      antidepressant treatment response in STARD (rs7997012; rs1928040) were analyzed
      for association with treatment response in two independent Caucasian samples of
      patients with a Major Depressive Episode. In the combined sample (n=637) SNP
      rs7997012 was significantly associated with remission after five weeks providing
      first replicative support for the initial finding, with, however, an inverse
      allelic association as compared to the STARD sample.

PMID- 19758790
TI  - The time course of unconditioned morphine-induced psychomotor sensitization
      mirrors the phosphorylation of FADD and MEK/ERK in rat striatum: role of PEA-15
      as a FADD-ERK binding partner in striatal plasticity.
AB  - Drugs of abuse induce behavioral neuroadaptations whose molecular mechanisms,
      partly known, are crucial to understanding drug addictions. The multifunctional
      adaptor Fas-associated protein with death domain (FADD) was recently associated
      with the induction of neuroplasticity. This study investigated the modulation of
      FADD and MAP kinase signaling, as well as their interactions with PEA-15
      (phosphoprotein enriched in astrocytes-15 kDa) and Akt1 pathways, during the
      expression of unconditioned morphine-induced psychomotor sensitization. In
      morphine-pretreated rats (10mg/kg during 5 days), a challenge dose of the opiate
      induced a robust psychomotor sensitization at early withdrawal (3 days, SW 3),
      but not after a prolonged abstinence period (14 days), which was coincident with
      an accelerated dopamine turnover in the striatum. Marked concomitant increases in
      the content of p-FADD (48%) and the activation of MEK-ERK (46-79%) were
      quantified during the short-term expression of morphine sensitization (SW 3, in
      the absence of morphine challenge). At SW 3, p-PEA-15, a FADD-ERK binding
      partner, was also upregulated (51%) as well as the activation of its
      phosphorylating Akt1 kinase (49%). Notably, the MEK inhibitor SL 327 attenuated
      (58%) the expression of morphine-induced psychomotor sensitization (SW 3) and
      fully prevented the upregulation of p-FADD, p-PEA-15 and p-Akt1 at SW 3. The
      results indicate that the activation of MEK/ERK, the upregulation of p-FADD and
      that of the linking partners PEA-15/Akt1 have a major role in mediating the short
      lasting expression of unconditioned psychomotor sensitization induced by morphine
      in rats.

PMID- 19758791
TI  - Preface. In honour of professor Hans Kuhn.

PMID- 19758792
TI  - [Emergence of invasive nonvaccine pneumococcal serotypes: 2 cases involving 19A
      and 10A serotypes].
AB  - The authors report 2 cases of invasive pneumococcal disease. One case consisted
      in occult bacteremia due to a 19A serotype in a child who had received 3 doses
      and a booster dose of the heptavalent pneumococcal conjugate vaccine (Prevenar).
      The 2nd case was pneumococcal meningitis due to a 10A serotype. The incidence of
      nonvaccine serotypes is increasing, notably the 19A serotype. They must be
      closely monitored because of the high antimicrobial resistance of certain
      strains.

PMID- 19758793
TI  - G-protein-coupled receptor 40 (GPR40) expression and its regulation in human
      pancreatic islets: the role of type 2 diabetes and fatty acids.
AB  - BACKGROUND AND AIMS: GPR40 is a membrane-bound receptor paired with medium and
      long-chain fatty acids (FFA) as endogenous ligands. Its acute activation
      potentiates insulin secretion from beta cells, whereas prolonged binding might
      contribute to the deleterious effects of chronic exposure to FFA. Little
      information is available on the expression of GPR40 and its regulation in human
      islets (HI). MATERIAL AND METHODS: HI were prepared by enzymatic digestion and
      gradient separation from the pancreas of 20 non-diabetic (Ctrl) and 13 type 2
      diabetic (T2DM) multiorgan donors, and functional and molecular studies were then
      performed. RESULTS: By qualitative and quantitative PCR experiments, mRNA
      expression was shown in HI. Both in T2DM islets and in Ctrl islets pre-exposed
      for 24 h to 1.0 mmol/l FFA (palmitate:oleate, 2:1), GPR40 mRNA expression was
      significantly reduced (p<0.01) in the T2DM cells as compared to Ctrl cells. A
      significant positive correlation was found between glucose-stimulated insulin
      secretion and GPR40 expression. CONCLUSIONS: These results show the expression of
      GPR40 in human pancreatic islets which are regulated by FFA. The finding that
      T2DM islets have a lower GPR40 expression, and the correlation of these genes
      with insulin secretion, raises the possibility of an involvement of GPR40 in
      human diabetes beta-cell dysfunction.

PMID- 19758794
TI  - ROS-mediated autophagy was involved in cancer cell death induced by novel
      copper(II) complex.
AB  - In this study, we investigated autophagy induced in HeLa cells by copper(II)
      complex of ethyl 2-[bis(2-pyridylmethyl)amino] propionate ligand (ETDPA)
      (formula: [(ETDPA)Cu(phen)](ClO4)2 (abbreviated as LCu),a novel synthetic
      copper(II) complex whose DNA binding activity has been proved. Cell viability,
      autophagic levels and generation of ROS were evaluated following the exposure to
      LCu. LCu-induced cell death in a dose- and time-dependent manner, which was
      demonstrated by enhanced fluorescence intensity of monodansylcadervarine (MDC),
      as well as elevated expression of autophagy-related protein MAP-LC3. These
      phenomena were all attenuated after pretreatment with autophagy inhibitors 3-MA
      or NH(4)Cl. Furthermore, our data indicated that LCu-triggered autophagy through
      ROS: cellular ROS levels were increased after LCu treatment, which was reversed
      by ROS scavenger NAC (N-acetylcysteine). As a consequence, Lcu-mediated autophagy
      was partly blocked by NAC. In summary, we synthesized a novel copper(II) complex
      and showed that this compound was effective in killing HeLa cells via ROS
      triggered autophagic pathway.

PMID- 19758795
TI  - Effects of total glucosides of paeony on oxidative stress in the kidney from
      diabetic rats.
AB  - TGP, extracted from the traditional Chinese herb root of Paeonia lactiflora pall,
      has been shown to have therapeutic effect in experimental diabetic nephropathy.
      However, its mechanism is not fully understood. In this study, the effects of TGP
      on oxidative stress were investigated in the kidney of diabetic rats induced by
      streptozotocin. TGP (50, 100, 200mg/kg) was orally administered once a day for 8
      weeks. TGP treatment in all three doses significantly lowered 24 h urinary
      albumin excretion rate in diabetic rats and attenuated glomerular volume. TGP
      treatment with 100 and 200mg/kg significantly reduced indices for
      tubulointerstitial injury in diabetic rats. The level of MDA was significantly
      increased in the kidney of diabetic rats and attenuated by TGP treatment at the
      dose of 200mg/kg. TGP treatment in a dose-dependent manner decreased the level of
      3-NT protein of the kidney which increased under diabetes. T-AOC was
      significantly reduced in diabetic rat kidney and remarkably increased by TGP
      treatment at the dose of 100 and 200mg/kg. Activity of antioxidant enzyme such as
      SOD, CAT was markedly elevated by TGP treatment with 200mg/kg. Western blot
      analysis showed that p-p38 MAPK and NF-kappaB p65 protein expression increased in
      diabetic rat kidney, which were significantly decreased by TGP treatment. It
      seems likely that oxidative stress is increased in the diabetic rat kidneys,
      while TGP can prevent diabetes-associated renal damage against oxidative stress.

PMID- 19758796
TI  - Computational design tools for synthetic biology.
AB  - Computer-aided design, pervasive in other engineering disciplines, is currently
      developing in synthetic biology. Concepts for standardization and hierarchies of
      parts, devices and systems provide a basis for efficient engineering in biology.
      Recently developed computational tools, for instance, enable rational (and
      graphical) composition of genetic circuits from standard parts, and subsequent
      simulation for testing the predicted functions in silico. The computational
      design of DNA and proteins with predetermined quantitative functions has made
      similar advances. The biggest challenge, however, is the integration of tools and
      methods into powerful and intuitively usable workflows-and the field is only
      starting to address it.

PMID- 19758797
TI  - Biomass production of papyrus (Cyperus papyrus) in constructed wetland treating
      low-strength domestic wastewater.
AB  - In this study, the pilot-scale constructed wetlands were fed with low-strength
      domestic wastewater to investigate the energy-capturing efficiency and plant
      productivity. Papyrus was a selected emergent macrophyte planted in the systems.
      The wastewater was intermittently fed to the systems, corresponding to the
      organic loading rates of 10, 16, 31, and 63 kg BOD/ha-d. With abundant sunshine
      in the tropical-climate area, papyrus converted solar radiation to biomass of
      about 2200-3100 g dry weight/m(2) from the two-month period of the experiments.
      Furthermore, the energy contents of papyrus are 16.2, 17.2, and 16.8 MJ/kg for
      culms, umbels, and total above-ground parts, respectively. From the plant
      productivity and the energy contents of papyrus obtained from this study, the
      energy capturing efficiencies can be estimated to be in the range of 4.4-6.0%,
      which are relatively high, compared with those of other plants.

PMID- 19758798
TI  - An innovative attached-growth biological system for purification of pond water.
AB  - This study applied the non-woven material from used diaper as the carrier for bio
      film process to purify the recycled water from a landscape pond at the Tainan
      City Municipal Culture Center (TCMCC), Taiwan. An on-site system was installed
      and the experiment was accomplished through three stages in 192 days with
      different time periods of 70 days, 63 days, and 59 days, respectively. The
      results showed that the non-woven media is functional for SS removal. The average
      SS removal of stages 1, 2, and 3 were 91%, 96%, and 95%, respectively. The
      highest SCOD removal efficiency of 90% occurred at stage 3. A significant color
      improvement of the pond water was achieved through this non-woven bio-carrier
      treatment system. Whole system can be without any maintenance for 139 days. The
      result indicated that the non-woven medium system was with a great potential in
      treating and recycling the pond water with stable operation and satisfactory
      removal performance.

PMID- 19758799
TI  - Composition and acaricidal activity of Lippia sidoides essential oil against two
      spotted spider mite (Tetranychus urticae Koch).
AB  - The essential oils from accessions of Lippia sidoides Cham. (Verbenaceae) were
      characterized by GC and GC/MS and investigated for their acaricidal activity
      against the two-spotted spider mite (Tetranychus urticae Koch). Twenty-nine
      compounds were identified with potential acaricidal activity. Glass receptacles
      were used as test chambers. For each dose and exposure time combination, three
      replicates were used. Each replicate consisted of 30 adult females of T. urticae,
      10 mites in each leaf disk of Canavalia ensiformis placed in a Petri dish.
      Increasing amounts of oil or terpene were applied on a blotting paper strip,
      fixed on the inner surface of the glass recipient cover, corresponding to 2, 4,
      6, 8, and 10 microL/L of air, respectively. Exposure periods were 24, 48, and 72
      h. Data obtained in these experiments were submitted to probit analysis. The
      essential oil of L. sidoides, thymol and carvacrol exhibited potent acaricidal
      activity against T. urticae.

PMID- 19758800
TI  - Performance evaluation of adding ethanol production into an existing combined
      heat and power plant.
AB  - In this paper, the configuration and performance of a polygeneration system are
      studied by modelling the integration of a lignocellulosic wood-to-ethanol process
      with an existing combined heat and power (CHP) plant. Data from actual plants are
      applied to validate the simulation models. The integrated polygeneration system
      reaches a total efficiency of 50%, meeting the heating load in the district
      heating system. Excess heat from the ethanol production plant supplies 7.9 MW to
      the district heating system, accounting for 17.5% of the heat supply at full
      heating load. The simulation results show that the production of ethanol from
      woody biomass is more efficient when integrated with a CHP plant compared to a
      stand-alone production plant. The total biomass consumption is reduced by 13.9%
      while producing the same amounts of heat, electricity and ethanol fuel as in the
      stand-alone configurations. The results showed that another feature of the
      integrated polygeneration system is the longer annual operating period compared
      to existing cogeneration. Thus, the renewable electricity production is increased
      by 2.7% per year.

PMID- 19758801
TI  - Recovery of plastic wastes from dumpsite as refuse-derived fuel and its
      utilization in small gasification system.
AB  - An effort to utilize solid wastes at dumpsite as refuse-derived fuel (RDF) was
      carried out. The produced RDF briquette was then utilized in the gasification
      system. These wastes were initially examined for their physical composition and
      chemical characteristics. The wastes contained high plastic content of 24.6
      44.8%, majority in polyethylene plastic bag form. The plastic wastes were
      purified by separating them from other components through manual separation and
      trommel screen after which their content increased to 82.9-89.7%. Subsequently,
      they were mixed with binding agent (cassava root) and transformed into RDF
      briquette. Maximum plastic content in RDF briquette was limit to 55% to maintain
      physical strength and maximum chlorine content. The RDF briquette was tested in a
      down-draft gasifier. The produced gas contained average energy content of 1.76
      MJ/m(3), yielding cold gas efficiency of 66%. The energy production cost from
      this RDF process was estimated as USD0.05 perkWh.

PMID- 19758802
TI  - Design and synthesis of substituted nicotinamides as inhibitors of soluble
      epoxide hydrolase.
AB  - A series of potent nicotinamide inhibitors of soluble epoxides hydrolase (sEH) is
      disclosed. This series was designed using structure-based deconstruction and a
      combination of two HTS hit series, resulting in hybrid analogs that retained the
      optimal potency from one series, and acceptable in vitro metabolic stability from
      the other. Structure-guided optimization of these analogs gave rise to nanomolar
      inhibitors of human sEH that had acceptable plasma exposure to qualify them as
      probes to determine the in vivo phenotypic consequences of sEH inhibition.

PMID- 19758803
TI  - Crosstalk in Met receptor oncogenesis.
AB  - The Met receptor tyrosine kinase (RTK) regulates several distinct biological
      processes, including cell scatter, cell invasion, cell survival and epithelial
      remodeling. MET is genetically altered through several mechanisms in multiple
      human cancers; these events are causally related to cancer initiation and
      progression, identifying Met as a potential therapeutic target. Recent evidence
      highlights additional roles for Met in cancer through crosstalk with other
      receptors and cell surface proteins. In this review, we discuss recent progress
      in our understanding of mechanisms of interaction between Met, the epidermal
      growth factor receptor family and other cell surface protein families, and how
      these contribute to signal crosstalk, oncogenesis and drug resistance.

PMID- 19758804
TI  - The use of mushroom-forming fungi for the production of N-glycosylated
      therapeutic proteins.
AB  - The market for N-glycosylated therapeutic proteins represents multi-billion
      dollars in sales and is growing more than 10% each year. This requires cost
      effective production platforms that display correct and homogeneous N
      glycosylation. Based on recent results, we propose to use mushroom-forming
      basidiomycetes for the production of N-glycosylated therapeutic proteins.

PMID- 19758805
TI  - An "omics" approach to uropathogenic Escherichia coli vaccinology.

PMID- 19758806
TI  - Postoperative morbidity and mortality following total knee arthroplasty with
      computer navigation.
AB  - The incidence of postoperative complications following computer navigated total
      knee arthroplasty is unknown. There is no published evidence to support decreased
      morbidity compared to standard conventional technique. The Nationwide Inpatient
      Sample database was used to identify 101,596 patients who underwent total knee
      arthroplasty in 2005. Of these patients, 1156 were coded as having a computer
      assisted procedure. Bivariate analysis and regression modeling were used to
      compare postoperative in-hospital outcomes between the computer-assisted and non
      navigated cohorts. We found no differences in postoperative mortality or
      complications for the majority of our measured outcomes. Under multivariate
      regression analysis, computer navigation was associated with a lower rate of
      postoperative cardiac complications (odds ratio 0.40, p=0.042), a shorter length
      of stay, and a trend towards fewer hematomas. Further clinical study is required
      to examine the possible association of computer navigation with postoperative
      morbidity following knee arthroplasty.

PMID- 19758807
TI  - Indene-based frameworks targeting the 5-HT6 serotonin receptor: ring constraint
      in indenylsulfonamides using cyclic amines and structurally abbreviated
      counterparts.
AB  - Further studies in quest of 5-HT(6) serotonin receptor ligands led to the design
      and synthesis of a few selected examples of N-(inden-5-yl)sulfonamides with a
      ring-constrained aminoethyl side chain at the indene 3-position, some of which
      exhibited a high binding affinity, such as the pyrrolidine analogue 28
      (K(i)=3nM). Moreover, the structurally abbreviated N-(inden-5-yl)sulfonamides
      showed K(i) values > or = 43 nM, which indicates that neither the N,N-aminoethyl
      nor the conformationally restricted aminoethyl side arm at the indene 3-position
      are required for binding. Selected compounds were then tested in a functional
      cAMP stimulation assay and found to act as 5-HT(6) antagonists, although with
      moderate potency at the micromolar level.

PMID- 19758808
TI  - Ursolic acid derivatives induce cell cycle arrest and apoptosis in NTUB1 cells
      associated with reactive oxygen species.
AB  - Twenty-three ursolic acid (1) derivatives 2-24 including nine new 1 derivatives
      5, 7-11, 20-22 were synthesized and evaluated for cytotoxicities against NTUB1
      cells (human bladder cancer cell line). Compounds 5 and 17 with an isopropyl
      ester moiety at C-17-COOH and a succinyl moiety at C-3-OH showed potent
      inhibitory effect on growth of NTUB1 cells. Compounds 23 and 24 with seco
      structures prepared from 1 also showed the increase of the cytotoxicity against
      NTUB1 cells. Exposure of NTUB1 to 5 (40 microM) and 23 (20 and 50 microM) for 24h
      significantly increased the production of reactive oxygen species (ROS) while
      exposure of NTUB1 to 5 (20 and 40 microM) and 23 (20 and 50 microM) for 48 h also
      significantly increased the production of ROS while exposure of cells to 17 did
      not increase the amount of ROS. Flow cytometric analysis exhibited that treatment
      of NTUB1 with 5 or 17 or 23 led to the cell cycle arrest accompanied by an
      increase in apoptotic cell death after 24 or 48 h. These data suggest that the
      presentation of G1 phase arrest and apoptosis in 5- and 23-treated NTUB1 for 24 h
      mediated through increased amount of ROS in cells exposed with 5 and 23,
      respectively, while the presence of G2/M arrest before accumulation of cells in
      sub-G1 phase in 5-treated cells for 48 h also due to increased amount of ROS in
      cells exposed with 5. The inhibition of tubulin polymerization and cell cycle
      arrest at G2/M following by apoptosis presented in the cell cycle of 23 also
      mediates through the increase amount of ROS induced by treating NTUB1 with 23 for
      48 h.

PMID- 19758809
TI  - Benzamide derivatives as dual-action hypoglycemic agents that inhibit glycogen
      phosphorylase and activate glucokinase.
AB  - A series of benzamide derivatives which can simultaneously inhibit glycogen
      phosphorylase (GP) and activate glucokinase (GK) were prepared and evaluated. The
      structure-activity relationships (SAR) of these compounds were also presented.
      Among these, compounds 12, 13l, 13q, and 13v showed moderate activities towards
      both GK and GP. Compound 13h inhibited hLGP with an IC(50) of 8.95 microM and
      activated GK with an EC(50) of 1.87 microM. The possible binding modes of
      compounds 12, 13l, 13h, and 13q with GP and GK were also explored by molecular
      docking simulation.

PMID- 19758810
TI  - The fine structure of coelomocytes in the sipunculid Phascolosoma esculenta.
AB  - Ultrastructural characteristics of coelomocytes of the sipunculid Phascolosoma
      esculenta were studied by transmission electron microscopy. There are several
      cell types in the coelomic fluid, including three kinds of granulocytes,
      vesicular cells, germ cells, amoebocytes, phagocytes, and erythrocytes; there are
      also a new cell complex which is composed of podocytes and granular cells. And
      several other cell types (erythrocyte and different kinds of granulocytes)
      gathering together was discovered in the coelomic fluid of P. esculenta.
      Functional interpretations were provided for these cells using morphological
      evidence. The coelomocytes from different sipunculid genera and Annelida were
      compared. The structural diversity of coelomocytes provides both taxonomic
      characteristics for discriminative identification and phylogenetic markers in
      Phascolosoma and other sipunculid taxa.

PMID- 19758811
TI  - Formation of zona radiata and ultrastructural analysis of egg envelope during
      oogenesis of Chinese perch Siniperca chuatsi.
AB  - During oocyte maturation, egg envelope undergoes a series of changes in structure
      and function. We investigated the follicular envelope, zona radiata and
      plasmalemma of Chinese perch, Siniperca chuatsi at five different developmental
      stages by light, scanning and transmission electron microscopy. An octopus-like
      structure in the zona radiata was observed for the first time. The increasing
      thickness of zona radiata during these stages suggests the microvilli's
      functional transition from transferring vital materials for the protection of the
      oocyte. That the egg envelope fully matures later than the oocyte is well
      supported by the disappearance of the follicular envelope. We have discovered
      several characteristic structures in the semi-floating egg and propose that the
      octopus-like structure is essential for oocyte migration and fertilization.

PMID- 19758812
TI  - Molecular cloning and characterization of five annexin genes from Indian mustard
      (Brassica juncea L. Czern and Coss).
AB  - Plant annexins constitute a multigene family having suggested roles in a variety
      of cellular processes including stress responses. We have isolated and
      characterized five different cDNAs of mustard, Brassica juncea (AnnBj1, AnnBj2,
      AnnBj3, AnnBj6 and AnnBj7) encoding annexin proteins using a RT-PCR/RACE-PCR
      based strategy. The predicted molecular masses of these annexins are
      approximately 36.0 kDa with acidic pIs. At the amino acid level, they share high
      sequence similarity with each other and with annexins from higher plants.
      Phylogenetic analysis revealed their evolutionary relationship with corresponding
      orthologous sequences in Arabidopsis and deduced proteins in various plant
      species. Expression analysis by semi-quantitative RT-PCR revealed that these
      genes are differentially expressed in various tissues. The expression patterns of
      these genes also showed regulation by various stress conditions such as exposure
      to signaling molecules, salinity and oxidative stress and wounding. Additionally,
      the in silico promoter analysis (of AnnBj1, AnnBj2 and AnnBj3) showed the
      presence of different cis-responsive elements that could respond to various
      stress conditions. These results indicate that AnnBj genes may play important
      roles in adaptation of plants to various environmental stresses.

PMID- 19758813
TI  - Simulative operation on congenital heart disease using rubber-like urethane
      stereolithographic biomodels based on 3D datasets of multislice computed
      tomography.
AB  - OBJECTIVE: Stereolithographic biomodelling is a technique where photosensitive
      liquid resin is polymerised with a pinpoint laser beam controlled by three
      dimensional (3D) datasets. This study was designed to assess whether a
      stereolithographic biomodelling technique is applicable for precise anatomical
      diagnosis and simulation surgery of complicated congenital heart disease.
      METHODS: Twelve stereolithographic biomodels were manufactured with multislice
      computed tomography (MSCT)-based 3D datasets. They were made of photosensitive
      liquid epoxy or urethane. RESULTS: All the solid epoxy and rubber-like urethane
      biomodels reproduced the complex anatomical structures of the arteries and veins
      in congenital heart diseases. Furthermore, the rubber-like urethane biomodels
      allowed the surgeon to cut and suture, thus facilitating the simulation of the
      surgical operation. CONCLUSIONS: Stereolithographic biomodelling is a promising
      technique for the preoperative practice and simulation of individual surgery.
      This technique would be useful in the planning of novel and innovative surgical
      procedures of congenital heart disease.

PMID- 19758814
TI  - Selective right ventricular impairment following coronary artery bypass graft
      surgery.
AB  - BACKGROUND: The right ventricle (RV) may be selectively impaired following
      coronary artery bypass graft (CABG) surgery. We tested this hypothesis in two
      study parts: a prospective cohort undergoing CABG, and a retrospective cross
      sectional cohort of heart-failure patients with and without a history of CABG.
      METHODS: In the prospective study, 20 patients undergoing CABG had
      echocardiography prior to surgery and 3 months postoperatively. In the
      retrospective study, 101 patients with established heart failure underwent
      echocardiography, 40 of whom had undergone previous CABG and 61 of whom had not.
      Myocardial tissue Doppler velocities were used as a measure of left and right
      ventricular function. To adjust for varying degrees of overall cardiac
      impairment, we calculated the ratio between the velocities of the RV and left
      ventricle (LV). RESULTS: In the prospective study, there was a significant fall
      in RV:LV ratio following CABG surgery. For S', the ratio fell from 2.27 to 1.13
      (50%, p<0.0001), for E' from 1.49 to 0.94 (37%, p<0.0001) and for A' from 1.66 to
      1.05 (37%, p<0.0001). In the retrospective study, the RV:LV ratio was lower in
      the CABG group compared with the non-CABG group for S' (by 32%, p<0.001), E' (by
      39%, p<0.001) and A' (by 37%, p<0.001). In the retrospective study, even when the
      CABG patients were compared with the ischaemic aetiology heart-failure patients
      without CABG, a similar relative impairment was seen: 25% in S' (p<0.001), 34% in
      E' (p<0.001) and by 38% in A' (p<0.002). CONCLUSIONS: Both prospectively and
      cross-sectionally, there is evidence of substantial, selective right ventricular
      impairment following CABG. These features cannot be explained simply by some
      general feature of ischaemia and, therefore, must be a consequence of surgery.

PMID- 19758815
TI  - Bronchopulmonary arteriovenous malformation - demonstrated by multidetector
      computed tomography angiography.

PMID- 19758816
TI  - Vascular endothelial growth factor C: the predicator of early recurrence in
      patients with N2 non-small-cell lung cancer.
AB  - OBJECTIVE: Mediastinal lymph node metastasis (N2) is a key prognostic factor for
      lung carcinoma. This study was undertaken to investigate the relationship between
      vascular endothelial growth factor C (VEGF-C) expression and postoperative early
      recurrence in patients with N2 non-small-cell lung cancer. METHODS: Cancer tissue
      samples from 92 patients with pN2 non-small-cell lung cancer and benign lung
      disease tissues samples from 30 patients were examined by reverse transcription
      polymerase chain reaction (RT-PCR) and immunohistochemistry assays to detect VEGF
      C expression. The difference of VEGF-C expression was compared by chi(2) test.
      All patients with N2 disease were evaluated within 1 year after surgery to detect
      early tumour recurrence. Cox regression analysis was performed to determine the
      risk factors of postoperative early recurrence of N2 lung cancer. RESULTS: VEGF-C
      mRNA expression was observed in 64 (70%) pN2 lung cancer tissues, but was not
      found in benign lung disease tissues. Early recurrence occurred in 43 patients
      (47%) at 1 year after operation. The main pattern was distant recurrence, and the
      most frequent sites were the brain and lung. The early recurrence rate in
      patients with positive VEGF-C expression was significantly higher than that of
      those with negative VEGF-C expression (P=0.006, log-rank test). Cox regression
      analysis revealed that positive VEGF-C expression in tumours (hazard ratio
      (HR)=2.523, P=0.037) was an independent risk factor of postoperative early
      recurrence of N2 lung cancer. CONCLUSIONS: VEGF-C expression was high in N2 lung
      cancer, with significant correlation to postoperative early recurrence. About one
      half of the patients with N2 non-small-cell lung cancer would develop recurrence
      disease within 1 year after surgery, frequently with mediastinal nodes, brain or
      lung metastases. VEGF-C might be a predictor of postoperative early recurrence in
      patients with N2 non-small-cell lung cancer.

PMID- 19758817
TI  - Aberrant left brachiocephalic vein.

PMID- 19758818
TI  - Long-term results after mitral valve repair in children.
AB  - OBJECTIVE: We analysed the long-term results of mitral valve (MV) repair in
      children. METHODS: We reviewed clinical records of 139 children (<18 years) who
      underwent MV repair between 1988 and 2007. Patients with atrioventricular septal
      defect, single ventricle or atrioventricular discordance were excluded. Median
      age was 2.3 years (2 months to 17.6 years), and 47 children (34%) were infants.
      Mitral regurgitation (MR) was predominant in 125 patients (90%), and 91 (73%) of
      these showed MR grade > or = 3. Mitral stenosis (MS) was predominant in 14
      patients (10%), and median mean pressure gradient across the MV was 9.0 mmHg (0
      20 mmHg). Associated cardiac lesions were present in 111 patients (80%) and were
      addressed concurrently in 105 patients. Various surgical techniques were used
      according to the functional and pathologic findings of MV. RESULTS: There was no
      early death. Median follow-up was 8 years (2 months to 20 years, 78% complete).
      Twenty-six patients required 29 MV re-operations, and 11 of these required MV
      replacements. At 15 years, freedom from MV re-operation and MV replacement was
      77% and 90%, respectively. Diagnosis of MS and MV status on discharge (MR grade >
      or =3 or MS gradient > or =10 mmHg) were significant risk factors for re
      operation. There were three late deaths, and the overall survival was 97% at 15
      years. Among 122 survivors with MR, 102 patients (84%) underwent echocardiography
      during follow-up. The degree of MR decreased significantly and only five patients
      showed MR grade 3. Among 14 survivors with MS, eight patients (57%) underwent
      echocardiography during follow-up. The degree of MS decreased significantly and
      median MS gradient was 2.8 mmHg (0-10 mmHg). All survivors remain in the NYHA
      class I or II. CONCLUSIONS: MV repair in children showed excellent survival,
      acceptable re-operation rate and satisfactory valve function at long-term follow
      up. Residual MV dysfunction was a significant risk factor for re-operation, but
      re-repair was successful in more than half of the patients who underwent re
      operation.

PMID- 19758819
TI  - Absorption and emission spectroscopic characterization of BLUF protein Slr1694
      from Synechocystis sp. PCC6803 with roseoflavin cofactor.
AB  - The wild-type BLUF protein Slr1694 from Synechocystis sp. PCC6803 (BLUF=blue
      light sensor using FAD) has flavin adenosine dinucleotide (FAD) as natural
      cofactor. This light sensor causes positive phototaxis of the marine
      cyanobacterium. In this study the FAD cofactor of the wild-type Slr1694 was
      replaced by roseoflavin (RoF) and the roseoflavin derivatives RoFMN and RoFAD
      during heterologous expression in a riboflavin auxotrophic E. coli strain. An
      absorption and emission spectroscopic characterization of the cofactor-exchanged
      Slr1694 (RoSlr) was carried out both under dark conditions and under illuminated
      conditions. The behaviour of RoF embedded in RoSlr in aqueous solution at pH 8 is
      compared with the behaviour of RoF in aqueous solution. The fluorescence of RoF
      and RoSlr is quenched by photo-induced twisted intra-molecular charge transfer at
      room temperature with stronger effect for RoF. The fluorescence quenching is
      diminished at liquid nitrogen temperature. Light exposure of RoSlr causes
      irreversible conversion of the protein embedded roseoflavins to 8-methylamino
      flavins, 8-dimethylamino-lumichrome and 8-methylamino-lumichrome.

PMID- 19758820
TI  - Association of serum amyloid A levels with adipocyte size and serum levels of
      adipokines: differences between men and women.
AB  - The aim of this study was to characterize the association between adipocyte
      enlargement and circulating levels of serum amyloid A (SAA). Furthermore, we
      wanted to search for possible associations with measures of glycemic control and
      levels of circulating adipokines and/or inflammatory markers in men and women
      with a large range in body mass index. The study cohort consisted of 167
      subjects, 114 non-diabetic and 53 with Type 2 diabetes. Adipocyte diameter as
      well as circulating levels of SAA, C-reactive protein (CRP), adiponectin, leptin,
      interleukin-6, tumor necrosis factor alpha, glucose and insulin were measured.
      Women had higher serum levels of SAA than men (p=0.044). SAA levels were weakly
      but positively correlated with BMI (p=0.043) and % body fat (p=0.027) in all
      subjects as well as subcutaneous adipocyte diameter (p=0.034) in women.
      Furthermore, in all subjects we found correlations between SAA levels and levels
      of CRP (p<0.001), interleukin-6 (p<0.001), leptin (p=0.003), insulin (p=0.006),
      HbA1c (p=0.02) and HOMA-IR (p=0.002). A majority of the correlations were
      strongest in women. In conclusion, serum levels of SAA are strongly correlated
      with serum levels of inflammatory markers as well as measures of glycemic
      control. There seems to be large sex differences in these associations suggesting
      that sex-specific factors need to be considered when analyzing SAA levels in
      relation to metabolic disease.

PMID- 19758821
TI  - Influence of size on apparent scrambling of sequence during CID of b-type ions.
AB  - We investigated the influence of peptide size on the apparent loss of sequence
      during collision-induced dissociation (CID) of b ions using a group of peptides
      containing from between 4 and 10 residues. Although scrambling of sequence for
      b3+ generated from tetrapeptides is minimal, significant formation of nondirect
      sequence ions (i.e., ions for which scrambling has apparently occurred) was
      observed for all larger b ions included in the study.

PMID- 19758822
TI  - Combined vaccines - case study.
AB  - Application of the principles outlined in the WHO Guideline on Stability
      Evaluation of Vaccines is complicated by the nature of combination vaccines.
      Differences in degradation rates among the immunogens impose the restriction that
      shelf life is based on the most labile component. There is also a testing
      challenge with numerous components held at different stages of production.

PMID- 19758823
TI  - Methodological aspects of SEMG recordings for force estimation--a tutorial and
      review.
AB  - Insight into the magnitude of muscle forces is important in biomechanics
      research, for example because muscle forces are the main determinants of joint
      loading. Unfortunately muscle forces cannot be calculated directly and can only
      be measured using invasive procedures. Therefore, estimates of muscle force based
      on surface EMG measurements are frequently used. This review discusses the
      problems associated with surface EMG in muscle force estimation and the solutions
      that novel methodological developments provide to this problem. First, some basic
      aspects of muscle activity and EMG are reviewed and related to EMG amplitude
      estimation. The main methodological issues in EMG amplitude estimation are
      precision and representativeness. Lack of precision arises directly from the
      stochastic nature of the EMG signal as the summation of a series of randomly
      occurring polyphasic motor unit potentials and the resulting random constructive
      and destructive (phase cancellation) superimpositions. Representativeness is an
      issue due the structural and functional heterogeneity of muscles. Novel methods,
      i.e. multi-channel monopolar EMG and high-pass filtering or whitening of
      conventional bipolar EMG allow substantially less variable estimates of the EMG
      amplitude and yield better estimates of muscle force by (1) reducing effects of
      phase cancellation, and (2) adequate representation of the heterogeneous activity
      of motor units within a muscle. With such methods, highly accurate predictions of
      force, even of the minute force fluctuations that occur during an isometric and
      isotonic contraction have been achieved. For dynamic contractions, EMG-based
      force estimates are confounded by the effects of muscle length and contraction
      velocity on force producing capacity. These contractions require EMG amplitude
      estimates to be combined with modeling of muscle contraction dynamics to achieve
      valid force predictions.

PMID- 19758824
TI  - Soy-protein consumption and kidney-related biomarkers among type 2 diabetics: a
      crossover, randomized clinical trial.
AB  - OBJECTIVE: Renal disease is a major problem among diabetic patients. The type of
      protein consumed may affect alterations in kidney-related biomarkers in these
      patients. This study sought to assess the effects of soy-protein consumption on
      renal-related markers among type 2 diabetic patients with nephropathy. METHODS: A
      crossover, randomized clinical trial was conducted among 14 patients (10 men and
      4 women). One diet contained 0.8 g/kg protein (70% animal and 30% vegetable
      proteins), and a similar diet contained the same amount of protein with 35%
      animal protein, 35% soy protein, and 30% other vegetable proteins. These two
      diets were prescribed in each phase of the trial for 7 weeks. There was a 4-week
      washout between the two phases of the study. RESULTS: Consumption of soy protein
      reduced urinary urea nitrogen (-0.9 +/- 0.8 vs. 0.2 +/- 0.6 mg/dL, respectively,
      SD; P < .001), proteinuria (-78 +/- 37 vs. 42 +/- 39 mg/day, respectively, SD; P
      < .001), blood sodium (-2 +/- 0.04 vs. 2.0 +/- 0.06 mg/dL, respectively, SD; P <
      .01), and serum phosphorus (-0.03 +/- 0.2 vs. 0.2 +/- 0.3 mg/dL, respectively,
      SD; P < .01) compared with animal protein. Serum and urinary creatinine, blood
      urea nitrogen, serum calcium, and potassium levels were not significantly changed
      in soy-protein versus anima-protein consumption. CONCLUSION: Soy-protein
      consumption reduces proteinuria in type 2 diabetes with nephropathy.

PMID- 19758825
TI  - Autogenous brachial-brachial fistula for vein access. Haemodynamic factors
      predicting outcome and 1 year clinical data.
AB  - Two-stage autogenous brachial vein-brachial artery access (ABBA) has been
      proposed as an option where adequate superficial vein is not available for the
      creation of conventional haemodialysis fistulae. METHODS: This report depicts the
      clinical outcome of a series of 17 consecutive patients who underwent ABBA in a
      single centre. Of the 17 patients, nine had had at least one previous
      arterioventricular (AV) fistula or graft, and eight were new to haemodialysis.
      Patencies were assessed using the Kaplan-Meier survival analysis. RESULTS: In 14
      patients, the brachial vein was transposed (82%) and the time to transposition
      ranged from 4 to 26 weeks (median time: 6 weeks). The functional patency rate was
      45.75% at 12 months. After stage one, all fistulas that went on to develop well
      had a brachial vein flow of at least 900 ml min(-1), and this was significantly
      higher than in fistulas that failed to develop (p=0.005). The maturation rate in
      our study was 65% and the median time to cannulation of the fistula was 8 weeks
      from the stage 1. Of the 17 patients, 12 (71%) experienced at least one
      complication. Ten (59%) demonstrated moderate-to-severe stenoses; eight of which
      necessitated angioplasty and/or percutaneous mechanical thrombolysis.
      CONCLUSIONS: ABBA was characterised by a high incidence of complications and a
      long period to achieve maturation. Despite close monitoring and a high rate of
      secondary interventions, the patency rate was low. With this experience, we now
      only consider it an alternative in patients without adequate superficial veins,
      who have had failed grafts or where there is a very high risk of infection.

PMID- 19758826
TI  - Hb M Dothan [beta 25/26 (B7/B8)/(GGT/GAG-->GAG//Gly/Glu-->Glu]; a new mechanism
      of unstable methemoglobin variant and molecular characteristics.
AB  - A new unstable beta globin chain variant associated with methemoglobin (Met-Hb)
      phenotype was found in a Caucasian infant. Molecular analysis of the beta globin
      gene using polymerase chain reaction (PCR) amplification and sequencing led to
      the detection of a new in frame deletion in exon-1. Direct sequencing of the PCR
      product revealed a 3 bp deletion (-GTG) between codons 25/26, which resulted in
      the loss of a single amino acid (-Gly). We propose that this newly discovered
      unstable M-hemoglobin (M-Hb) variant, named Hb Dothan [GGT/GAG-->GAG//Gly/Glu-
      >Glu], is caused by a shift in the amino acid sequence and altered packing of the
      B and E helices during beta globin synthesis, and also changes the orientation of
      the critical proximal and distal histidine in the F and E helices respectively.
      Phenotype/Genotype features and molecular characteristics of this new beta chain
      are presented in this communication.

PMID- 19758827
TI  - Ultrasound-guided block of the sciatic and femoral nerves in dogs: a descriptive
      study.
AB  - Ten canine cadavers were used to investigate the anatomy and ultrasonographic
      approaches to the sciatic (ScN) and femoral (FN) nerves and to assess the
      accuracy of an ultrasound (US) guided technique to locate and block these nerves
      in the dog. The nerves of four sedated dogs were sought using US, blocked with 1%
      lidocaine and successful location confirmed by peripheral neurostimulation. The
      ScN was identified by US in all cases whereas the FN was not located in all
      cases. This study validates the usefulness of the US-guided technique to locate
      and block the ScN at the midfemoral level but the acoustic window of the inguinal
      region was less successful for locating and blocking the FN.

PMID- 19758828
TI  - Control of bovine fasciolosis in dairy cattle in Switzerland with emphasis on
      pasture management.
AB  - Thirty-two dairy cattle farms with fasciolosis as an established herd problem
      were visited and divided into groups according to the location of the habitats of
      the intermediate host of Fasciola hepatica. The farms were revisited 4-5 years
      later and those that had followed the recommended measures were compared to those
      that had not. Egg shedding and seroprevalence was significantly reduced in cows
      on farms complying with the control recommendations but was not reduced on farms
      that had not complied.

PMID- 19758829
TI  - Association of Stenotrophomonas maltophilia infection with lower airway disease
      in the horse: a retrospective case series.
AB  - Stenotrophomonas maltophilia is being reported with increasing frequency as a
      human nosocomial pathogen, especially among immuno-compromised patients. To the
      authors' knowledge, this pathogen has not previously been associated with lower
      airway disease in the horse. In this paper the clinical findings, laboratory
      diagnosis and response to treatment of seven cases of respiratory infection with
      S. maltophilia in horses, presented at three equine referral hospitals in Denmark
      in 2007, are described. In all cases there was a clinical history of chronic
      coughing and abundant mucopurulent exudate was observed in the lower trachea on
      endoscopy. On culture of tracheal aspirate, grey, slow-growing colonies,
      identified as S. maltophilia by both API 20NE identification and 16s ribosomal
      DNA sequencing, were identified. All isolates had a similar antibiotic
      susceptibility pattern characterised by resistance to all penicillins and
      cephalosporins, and to imipenem, gentamicin, amikacin and rifampicin. Ribotyping
      and pulsed-field gel electrophoresis of the S. maltophilia isolates from
      different patients indicated that they were either indistinguishable or closely
      related. This study indicates that S. maltophilia can be associated with chronic
      lower airway disease in the horse and provides useful initial insights into the
      diagnosis, therapy and epidemiology of this novel condition.

PMID- 19758830
TI  - Serum concentrations of the derivatives of reactive oxygen metabolites (d-ROMs)
      in dogs with leishmaniosis.
AB  - Leishmania infantum interferes with the oxidative metabolism of phagocytes. In
      order to assess whether derivatives of reactive oxygen metabolites (d-ROMs)
      decrease due to infection or increase due to inflammation, d-ROMs were measured
      in serum collected from control dogs (Group 1; n = 12), from dogs seropositive
      for Leishmania either symptomatic (Group 2; n = 27) or not (Group 3; n = 14), and
      from dogs with other diseases (Group 4; n = 16). The concentrations of d-ROMs in
      the four groups, expressed in Carratelli Units (U CARR) were, respectively, 75.4
      +/- 39.5 (median, 81.6), 108.2 +/- 96.3 (73.4), 73.5 +/- 62.2 (62.0), 127.7 +/-
      97.3 (94.3). There were no significant differences between groups, but dogs with
      values higher than the reference interval were found, mostly in Groups 2 and 4
      (which had serum C-reactive protein levels consistent with inflammation), whilst
      low values were occasionally found in Groups 2 and 3. Inflammation may mask
      decreases in d-ROMs induced by Leishmania infection.

PMID- 19758831
TI  - A pulsed EPR method to determine distances between paramagnetic centers with
      strong spectral anisotropy and radicals: the dead-time free RIDME sequence.
AB  - Methods to determine distances between paramagnetic metal centers and radicals
      are scarce. This is unfortunate because paramagnetic metal centers are frequent
      in biological systems and so far have not been employed much as distance markers.
      Successful pulse sequences that directly target the dipolar interactions cannot
      be applied to paramagnetic metal centers with fast relaxation rates and large g
      anisotropy, if no echos can be detected and the excitation bandwidth is not
      sufficient to cover a sufficiently large part of the spectrum. The RIDME method
      Kulik et al. (2002) [20] circumvents this problem by making use of the T(1)
      induced spin-flip of the transition-metal ion. Designed to measure distance
      between such a fast relaxing metal center and a radical, it suffers from a dead
      time problem. We show that this is severe because the anisotropy of the metal
      center broadens the dipolar curves, which therefore, only can be analyzed if the
      full curve is known. Here, we introduce five-pulse RIDME (5p-RIDME) that is
      intrinsically dead-time free. Proper functioning of the sequence is demonstrated
      on a nitroxide biradical. The distance between a low-spin Fe(III) center and a
      spin label in spin-labeled cytochrome f shows the complete dipolar trace of a
      transition-metal ion center and a spin label, yielding the distance expected from
      the structure.

PMID- 19758832
TI  - Primary retroperitoneal abscesses due to Rhodococcus equi in a patient with
      severe nephrotic syndrome: successful antibiotic treatment with linezolid and
      tigecycline.
AB  - We present a case of Rhodococcus equi primary retroperitoneal abscesses without
      pulmonary involvement in an immunocompromised patient with severe nephrotic
      syndrome. No risk factors for exposure to R. equi were present. The infection was
      successfully treated with long-term combination antibiotic treatment including
      linezolid and tigecycline.

PMID- 19758833
TI  - Comparative analysis of methods for automatic detection and quantification of
      microvolt T-wave alternans.
AB  - Microvolt T-wave alternans (TWA), consisting of every-other-beat changes in ECG T
      wave morphology, is an index of susceptibility to malignant ventricular
      arrhythmias, requiring automatic techniques to be identified. Five of these,
      namely, fast-Fourier-transform spectral method (FFTSM), complex-demodulation
      method (CDM), modified-moving-average method (MMAM), Laplacian-likelihood-ratio
      method (LLRM) and adaptive-match-filter method (AMFM), were applied here to
      simulated and sample clinical data. The aim was to compare individual methods
      ability to properly identify stationary and time-varying TWA, avoiding false
      positive detections. The MMAM provided false-positive TWA when applied to
      simulated ECGs affected by amplitude variability, but TWA. Stationary TWA was
      properly quantified by the MMAM and, occasionally, underestimated by all other
      methods. The AMFM properly identified time-varying TWA. By contrast, the FFTSM
      detected not-stationary TWA as stationary, the MMAM introduced a time-delay in
      the estimated TWA-amplitude signal, while the CDM and LLRM were reliable only in
      the presence of slow-varying TWA. Altogether, the AMFM accomplished the best
      compromise between the needs to avoid false-positive TWA and to detect and
      characterize true-positive TWA. Results of our simulation approach were useful to
      explain different TWA levels measured by each competing methods applied to sample
      Holter ECGs from healthy subjects and coronary artery disease patients.

PMID- 19758834
TI  - The impact of duration of residence on cause-specific mortality: a cohort study
      of migrants from the Former Soviet Union residing in Israel and Germany.
AB  - A cohort study of migrants from the Former Soviet Union in Israel (N=528,848) and
      in Germany (N=34,393) was conducted. The impact of length of residence on cause
      specific mortality was investigated using Poisson regression and differences
      between the migrant groups were assessed. In both migrant cohorts, all cause
      mortality in males but not in females significantly decreased with increasing
      duration of residence (RR=0.76, 95% CI: 0.73-0.79 for 9+years of residence
      compared to 0-3 years), specifically in Israel for infectious diseases, cancer
      and CVD. For male and female migrants in Israel there was a large reduction in
      external cause mortality. The cancer risk in male migrants declined from 1 to
      0.76 (95% CI: 0.69-0.83) and in female migrants to 0.85 (95% CI: 0.78-0.93) after
      nine and more years of stay. Adjusting for several covariables, there were
      differences between migrants in the cause of death patterns in the two host
      countries, which may be associated with differences in their initial conditions
      or with effects of the destination country. The study highlights the need for
      migrant-specific prevention approaches.

PMID- 19758836
TI  - Experimental approaches for the discovery and characterization of regulatory
      small RNA.
AB  - Following the pioneering screens for small regulatory RNAs (sRNAs) in Escherichia
      coli in 2001, sRNAs are now being identified in almost every branch of the
      eubacterial kingdom. Experimental strategies have become increasingly important
      for sRNA discovery, thanks to increased availability of tiling arrays and fast
      progress in the development of high-throughput cDNA sequencing (RNA-Seq). The new
      technologies also facilitate genome-wide discovery of potential target mRNAs by
      sRNA pulse-expression coupled to transcriptomics, and immunoprecipitation with
      RNA-binding proteins such as Hfq. Moreover, the staggering rate of new sRNAs
      demands mechanistic analysis of target regulation. We will also review the
      available toolbox for wet lab-based research, including in vivo and in vitro
      reporter systems, genetic methods and biochemical co-purification of sRNA
      interaction partners.

PMID- 19758835
TI  - Topographic maps in human frontal and parietal cortex.
AB  - Retinotopic mapping of functional magnetic resonance (fMRI) responses evoked by
      visual stimuli has resulted in the identification of many areas in human visual
      cortex and a description of the organization of the visual field representation
      in each of these areas. These methods have recently been employed in conjunction
      with tasks that involve higher-order cognitive processes such as spatial
      attention, working memory, and planning and execution of saccadic eye movements.
      This approach has led to the discovery of multiple areas in human parietal and
      frontal areas, each containing a topographic map of visual space. In this review,
      we summarize the anatomical locations, visual field organization, and functional
      specialization of these new parietal and frontal topographic cortical areas. The
      study of higher-order topographic cortex promises to yield unprecedented insights
      into the neural mechanisms of cognitive processes and, in conjunction with
      parallel studies in non-human primates, into the evolution of cognition.

PMID- 19758837
TI  - Synthesis and characterization of the luminescent lanthanide complexes with two
      similar benzoic acids.
AB  - 2-((4-Methoxyphenoxy) carbonyl) benzoic acid, 2-(1-methoxyvinyl) benzoic acid and
      their rare earth complexes LnL(2)(OH).3H(2)O (Ln=La, Eu, Tb) were synthesized and
      characterized by means of elemental analysis, FTIR, (1)H NMR, UV and luminescence
      spectroscopy. The FTIR and (1)H NMR results show that the carboxylic groups in
      the complexes coordinated to the rare earth ions in the form of one dentate, and
      the ester carboxylic groups have taken part in the coordination. Among these
      complexes, Eu(III) complexes and Tb(III) complexes exhibit characteristic
      fluorescence with comparatively high brightness and good monochromaticity, which
      indicated that the ligands of HL(I) and HL(II) are good organic chromophore to
      absorb and transfer energy to metal ions.

PMID- 19758838
TI  - Study on the interaction among molecules and the determination of DNA by light
      scattering with a new type rhodanine derivative.
AB  - In this paper the resonance Rayleigh scattering (RRS) and second-order scattering
      (SOS) spectrums of interaction between deoxyribonucleic acid (DNA) and 3-(4'
      methylphenyl)-5-(2'-sulfophenylazo) rhodanine (4MRASP) in the environment of
      surface active substance sodium dodecyl sulfate (SDS) were reported. The light
      scattering intensity of 4MRASP was enhanced obviously and directly proportional
      to the concentrations of DNA when DNA was present. Based on this, two new
      determination methods of DNA were established with high sensitivity and
      selectivity, and the limits of detection were 8.00 and 1.07ngmL(-1). They were
      applied to the determination of trace amounts of nucleic acid in synthetic and
      practical samples with satisfactory results. At last, the active mechanism among
      molecules was studied by ultraviolet spectrum, scattering spectrum and
      thermodynamics, which showed that the active force was changed from hydrophobic
      force to electrostatic force before and after SDS was added, and the mechanism of
      sensitization effect of SDS was proposed.

PMID- 19758839
TI  - Improvement in the aetiological diagnosis of acute hepatitis C: a diagnostic
      protocol based on the anti-HCV-IgM titre and IgG Avidity Index.
AB  - BACKGROUND: The gold standard for the diagnosis of acute hepatitis C (AHC) is
      seroconversion to anti-HCV/HCV-RNA positivity, an occurrence frequently missed in
      clinical practice. OBJECTIVES: This study aims to diagnose AHC by the combined
      use of the HCV Avidity Index (HCV-AI) and HCV-IgM titre. STUDY DESIGN: We
      enrolled 45 patients with AHC diagnosed by seroconversion to anti-HCV/HCV-RNA
      positivity and 36 with exacerbation of chronic hepatitis C (e-CHC) diagnosed at
      least 1 year earlier. HCV-IgM titres were determined by a commercial enzyme
      linked immunosorbent assay (ELISA) and HCV-AI by an ELISA for detection of HCV
      IgG with a partial modification. For each test, specific cut-off values at four
      selected checking points were established during the observation (<10 days, 11-15
      days, 16-20 days and >20 days from the onset of symptoms): for the HCV-IgM assay,
      the highest value in e-CHC +5% and for HCV-AI assay, the lowest value in e-CHC 
      5%. RESULTS: Around 90% of patients with AHC or e-CHC were correctly diagnosed at
      all checking points by combining the results of both tests. This practice
      afforded an improvement in sensitivity for the diagnosis of AHC, with the highest
      values at first and third checking points (92.3% and 92.6%, respectively) and an
      improvement in negative predictive value (NPV), with the highest value at first
      checking point (92.6%). CONCLUSIONS: The diagnosis of AHC, made by seroconversion
      to anti-HCV/HCV-RNA positivity, was confirmed in more than 90% of patients by
      combining the results of IgG Avidity Index (IgG-AI) and HCV-IgM obtained in a
      single serum sample.

PMID- 19758840
TI  - Early effects of drugs responsible for DRESS on HHV-6 replication in vitro.

PMID- 19758841
TI  - Development of a real-time multiplex RSV detection assay for difficult
      respiratory samples, using ultrasone waves and MNAzyme technology.
AB  - BACKGROUND: Elderly infected with Human Respiratory Syncytial Virus (RSV) often
      bear low viral loads that stay below the detection limits of commercial assays. A
      more sensitive detection of RSV infections can improve patient management, guide
      containment strategies, and possibly prevent morbidity and mortality among
      populations most severely affected by RSV. OBJECTIVE: To test the sensitivity for
      RSV detection by using an alternative extraction method in combination with a new
      amplification procedure. STUDY DESIGN: Nasopharyngeal washes and sputum samples
      (n=78) form clinical cases, and broncheo-alveolar lavages (n=27) from an
      experimental RSV rat model were obtained. An ultrasone-based RNA extraction
      method was combined with a multi-component Nucleic Acid enzymes (MNAzyme)
      amplification procedure for simultaneous detection of RSV-A, RSV-B, and an
      Internal Extraction control IEC. RESULTS: Compared to standard real-time PCR
      technology, this method resulted in an increased detection sensitivity, ranging
      from 0.9 to 4.93 log (average 2.05+/-1.01) for RSV-A and 0.76 to 4.28 log
      (average 1.30+/-0.92) for RSV-B. CONCLUSIONS: An ultrasone-based extraction
      method with MNAzyme amplification resulted in improved detection of RSV in
      different respiratory samples, including sputum. This generic method for nucleic
      acid extraction should be readily applicable for any other respiratory pathogen.

PMID- 19758842
TI  - Lack of habituation in the light adapted flicker electroretinogram of normal
      subjects: a comparison with pattern electroretinogram.
AB  - OBJECTIVE: Sustained pattern stimulation (SPS) induces habituation in the normal
      pattern electroretinogram (PERG). In this study, the authors evaluated whether
      sustained flicker stimulation (SFS) induces habituation in the normal flicker ERG
      (FERG). METHODS: FERGs were elicited in normal volunteers by an 8Hz flicker
      stimulus, presented continuously over 3 min after 20 min of light adaptation. One
      stimulus temporal period was sampled and averaged in packets (n=20) of 60 events,
      each of 8s duration. Amplitudes and phases of the response 1st and 2nd harmonics
      (1F and 2F, respectively) were measured. FERG results were compared with those
      obtained by recording PERGs with a similar SPS paradigm. RESULTS: During SFS,
      FERG 2F showed a modest increase in amplitude (about 25%, p<0.05). No changes
      were observed for the 1F amplitude and for the phase of both components. In
      contrast, PERG amplitude showed SPS-induced habituation, described by an
      exponential decay with a time constant of approximately 20s. CONCLUSIONS: The
      normal FERG, unlike PERG, does not show habituation, suggesting that the adaptive
      changes of retinal neurons underlying FERG are different from those of PERG
      generators. SIGNIFICANCE: Our findings may have implications for diagnosis and/or
      pathophysiology of retinal disorders involving the inner retina.

PMID- 19758843
TI  - Feasibility of testing three salivary stress biomarkers in relation to
      naturalistic traffic noise exposure.
AB  - BACKGROUND AND OBJECTIVES: Stress dependent alterations of the salivary
      biomarkers alpha-amylase (sAA), salivary chromogranin A (sCgA) and salivary
      cortisol (sC) have been reported in numerous studies recently. The aim of this
      pilot study was to investigate the feasibility of testing sAA, sCgA and sC in
      relation to naturalistic traffic noise exposure in order to monitor a direct
      stress response in a laboratory setup. METHODS: A total of twenty study
      participants were exposed to binaurally recorded naturalistic traffic noise
      samples containing 75 dB (L(A,)eq) for 20 minutes via a loudspeaker system.
      Saliva was collected directly before and after defined exposure to naturalistic
      traffic noise. Determination of sAA was performed enzymatically on a Hitachi 912
      laboratory analyzer, sCgA was determined by ELISA technique and sC was determined
      using a RIA assay. RESULTS AND CONCLUSIONS: There was a significant increase of
      sAA and sC concentrations after traffic noise exposure (p=0.045; p=0.01), whereas
      for sCgA this was not observed (p=0.48). Measuring of sAA and sC appear to be
      feasible to investigate direct stress effects in relation to naturalistic traffic
      noise exposure in a laboratory setup. Considering the small sample size of this
      pilot study, these observations need to be further proved in a larger explorative
      study.

PMID- 19758844
TI  - Stress hormones: physiological stress and regulation of metabolism.
AB  - Stress, defined as a state of threatened homeostasis, mobilizes a complex
      spectrum of adaptive physiologic and behavioral responses that aim to re
      establish the challenged body homeostasis. The hypothalamic-pituitary-adrenal
      (HPA) axis and the sympathetic nervous system (SNS) constitute the main effector
      pathways of the stress system, mediating its adaptive functions. In western
      societies, indices of stress correlate with increasing rates of both obesity and
      metabolic syndrome which have reached epidemic proportions. Recent data indicate
      that chronic stress, associated with mild hypercortisolemia and prolonged SNS
      activation, favors accumulation of visceral fat and contributes to the clinical
      presentation of visceral obesity, type 2 diabetes, and related cardiometabolic
      complications. Reciprocally, obesity promotes a systemic low-grade inflammation
      state, mediated by increased adipokine secretion, which can chronically stimulate
      the stress system.

PMID- 19758846
TI  - Direct electron transfer and electrocatalysis of hemoglobin in ZnO coated
      multiwalled carbon nanotubes and Nafion composite matrix.
AB  - ZnO coated multiwalled carbon nanotubes (ZnO-MWCNTs) nano-composite was
      synthesized by the hydrothermal method and expected to offer a promising template
      for biosensor fabrication due to satisfying biocompatibility and improved
      properties. The ZnO-MWCNTs nano-composite was mixed with Nafion solution to form
      a composite matrix for the fabrication of hemoglobin (Hb) biosensor. This
      composite matrix combined the advantages of inorganic composite (ZnO-MWCNTs) and
      organic polymer (Nafion) and could promote the direct electron transfer of Hb.
      The Hb/ZnO-MWCNTs/Nafion film exhibited a pair of well-defined, quasi-reversible
      redox peaks with a formal potential of -0.353V (vs. SCE), characteristic of heme
      redox couple (Fe(III)/Fe(II)) of Hb. Hb retained its near-native conformation in
      the composite film. The immobilized Hb showed fast and excellent electrocatalytic
      activity to H(2)O(2) with a linear range from 2x10(-7) to 1.2x10(-5)M, and the
      detection limit was 8.4x10(-8)M. The sensitivity and apparent Michaelis-Menten
      constant were 1.31A/(M x cm(2)) and 82.8microM, respectively, which indicated
      that Hb had a high affinity to H(2)O(2). This biosensor also showed excellent
      electrocatalytic activity towards trichloroacetic acid.

PMID- 19758847
TI  - Purification and partial characterization of Cu/Zn superoxide dismutase from
      Kluyveromyces marxianus yeast.
AB  - A new thermostable Cu/Zn SOD from a thermotolerant yeast strain Kluyveromyces
      marxianus NBIMCC 1984 has been purified and characterized. The purification
      procedure comprises thermal treatment and dialysis, ion-exchange chromatography
      and chromatofocusing. The methodology is a rapid, efficient and highly specific,
      generating pure preparation (specific activity 996 U mg of protein(-1)) with a
      yield of 53%. The purified enzyme is a homodimer with Mw of 34,034 Da and has
      high N-terminal homology with other yeasts' Cu/Zn SOD enzymes. The protein is
      characterized with some unique features such as-thermostability (t(1/2) at 70
      degrees C=30 min), pH stability in the alkaline range (7.5-8.5) and resistance to
      inhibitors and variety of chemicals. These characteristics reveal possibilities
      for wide practical application of K. marxianus Cu/Zn SOD enzyme.

PMID- 19758845
TI  - High-throughput screening for inhibitors of Mycobacterium tuberculosis H37Rv.
AB  - There is an urgent need for the discovery and development of new antitubercular
      agents that target new biochemical pathways and treat drug resistant forms of the
      disease. One approach to addressing this need is through high-throughput
      screening of medicinally relevant libraries against the whole bacterium in order
      to discover a variety of new, active scaffolds that will stimulate new biological
      research and drug discovery. Through the Tuberculosis Antimicrobial Acquisition
      and Coordinating Facility (www.taacf.org), a large, medicinally relevant chemical
      library was screened against M. tuberculosis strain H37Rv. The screening methods
      and a medicinal chemistry analysis of the results are reported herein.

PMID- 19758848
TI  - Serum complement-reactive protein (CRP) trends following local and free-tissue
      reconstructions for traumatic injuries or chronic wounds of the lower limb.
AB  - BACKGROUND: Soft-tissue reconstructions of the lower limb for open fractures,
      chronic infections and nonunion carry a high risk of infection, nonunion,
      osteomyelitis and amputation. Inflammatory markers can be difficult to interpret
      in the context of recent surgery and trauma and little is known of their
      behaviour. AIM: To profile the behaviour of complement-reactive protein (CRP)
      following soft-tissue reconstructions for the lower limb performed for acute
      injuries(open fractures) and chronic wounds(nonunion and osteomyelitis). PATIENTS
      AND METHODS: Patients who had soft-tissue reconstructions following open
      fractures of the lower limbs, chronic infection, osteomyelitis and nonunion were
      identified and their notes and postoperative CRP levels reviewed. RESULTS: 52
      patients were identified. 41 reached peak CRP < or =4 days of surgery. A peak CRP
      >4 days indicated infection or further surgery (p<0.01). Acute and chronic groups
      showed a peak in mean CRP at day 2. Chronic wound patients showed significantly
      elevated CRP levels compared to acute wound patients at day 7 (p=0.05) and 8
      (p<0.001). Muscle and fasciocutaneous flaps showed similar CRP profiles. Patients
      with nonunion or deep infections showed persistently elevated CRP levels.
      CONCLUSIONS: CRP peaks on day 2 following soft-tissue coverage and falls
      thereafter. Peaks after day 4 indicate infective complications or further
      surgery. Patients with chronic wounds show a slower decrease in their CRP.
      Persistently elevated CRP following surgery is associated with infection and
      nonunion.

PMID- 19758849
TI  - Functional imaging of spinal cord electrical activity from its evoked magnetic
      field.
AB  - This paper investigates dynamic source imaging of the spinal cord
      electrophysiological activity from its evoked magnetic field by applying the
      spatial filter version of standardized low-resolution brain electromagnetic
      tomography (sLORETA). Our computer simulation shows that the sLORETA-based
      spatial filter can reconstruct the four current sources typically associated with
      the elicitation of the spinal cord evoked magnetic field (SCEF). The results from
      animal experiments show that significant changes in the latency and intensity of
      the reconstructed volume current arise near the location of the artificial
      incomplete conduction block. The results from the human SCEF show that the SCEF
      source imaging can visualize the dynamics of the volume currents and other nerve
      electrical activity propagating along the human spinal cord. These experimental
      results demonstrate the potential of SCEF source imaging as a future clinical
      tool for diagnosing cervical spinal cord disorders.

PMID- 19758850
TI  - Automatic segmentation and classification of multiple sclerosis in multichannel
      MRI.
AB  - We introduce a multiscale approach that combines segmentation with classification
      to detect abnormal brain structures in medical imagery, and demonstrate its
      utility in automatically detecting multiple sclerosis (MS) lesions in 3-D
      multichannel magnetic resonance (MR) images. Our method uses segmentation to
      obtain a hierarchical decomposition of a multichannel, anisotropic MR scans. It
      then produces a rich set of features describing the segments in terms of
      intensity, shape, location, neighborhood relations, and anatomical context. These
      features are then fed into a decision forest classifier, trained with data
      labeled by experts, enabling the detection of lesions at all scales. Unlike
      common approaches that use voxel-by-voxel analysis, our system can utilize
      regional properties that are often important for characterizing abnormal brain
      structures. We provide experiments on two types of real MR images: a multichannel
      proton-density-, T2-, and T1-weighted dataset of 25 MS patients and a single
      channel fluid attenuated inversion recovery (FLAIR) dataset of 16 MS patients.
      Comparing our results with lesion delineation by a human expert and with
      previously extensively validated results shows the promise of the approach.

PMID- 19758851
TI  - Robust detection of premature ventricular contractions using a wave-based
      Bayesian framework.
AB  - Detection and classification of ventricular complexes from the ECG is of
      considerable importance in Holter and critical care patient monitoring, being
      essential for the timely diagnosis of dangerous heart conditions. Accurate
      detection of premature ventricular contractions (PVCs) is particularly important
      in relation to life-threatening arrhythmias. In this paper, we introduce a model
      based dynamic algorithm for tracking the ECG characteristic waveforms using an
      extended Kalman filter. The algorithm can work on single or multiple leads. A
      "polargram"--a polar representation of the signal--is introduced, which is
      constructed using the Bayesian estimations of the state variables. The polargram
      allows the specification of a polar envelope for normal rhythms. Moreover, we
      propose a novel measure of signal fidelity by monitoring the covariance matrix of
      the innovation signals throughout the filtering procedure. PVCs are detected by
      simultaneous tracking the signal fidelity and the polar envelope. Five databases,
      including 40 records from MIT-BIH arrhythmia database, are used for
      differentiating normal, PVC, and other beats. Performance evaluation results show
      that the proposed method has an average detection accuracy of 99.10%, aggregate
      sensitivity of 98.77%, and aggregate positive predictivity of 97.47%.
      Furthermore, the method is capable of 100% accuracy for records that contain only
      PVCs and normal sinus beats. The results illustrate that the method can
      contribute to, and enhance the performance of clinical PVC detection.

PMID- 19758852
TI  - A novel concept for a prosthetic hand with a bidirectional interface: a
      feasibility study.
AB  - A conceptually novel prosthesis consisting of a mechatronic hand, an
      electromyographic classifier, and a tactile display has been developed and
      evaluated by addressing problems related to controllability in prosthetics:
      intention extraction, perception, and feeling of ownership. Experiments have been
      performed, and encouraging results for a young transradial amputee are reported.

PMID- 19758853
TI  - An implantable microactuated intrafascicular electrode for peripheral nerves.
AB  - Important advancements have been recently achieved in the field of neural
      interfaces to restore lost sensory and motor functions. The aim of this letter
      was to develop an innovative approach to increase the selectivity and the
      lifetime of polyimide-based intrafascicular electrodes. The main idea was to
      obtain a neural interface that is able to restore a good signal quality by
      improving the electrical connection between the active sites and the surrounding
      axons. The high flexibility of polyimide-based neural interfaces allows to embed
      microactuators in the interface core and achieve desired microdisplacements of
      the active sites. Nearly equiatomic nickel-titanium alloy was selected as a
      microactuator because of its shape memory effect. A single TiNi thin film was
      obtained by dc magnetron sputtering, and was segmented into four distinct
      sectors. This solution allowed the independent actuation of the different active
      sites (multiactuation). A corrugated profile was impressed to the new actuated
      intraneural (ACTIN) interface. The active sites were positioned in correspondence
      to the peaks of the corrugation, thus maximizing the effects of the single
      actuations. The technological results, the electrical properties, the thermal
      behavior, and eventually, the actuation performances of the current ACTIN
      prototype are shown and discussed. The actuation cycle was thermally compatible
      for biomedical applications. Promising results were obtained from the current
      ACTIN prototype with an average controlled movement of 7 microm of the peaks.

PMID- 19758854
TI  - Convolution power spectrum analysis for FMRI data based on prior image signal.
AB  - Functional MRI (fMRI) data-processing methods based on changes in the time domain
      involve, among other things, correlation analysis and use of the general linear
      model with statistical parametric mapping (SPM). Unlike conventional fMRI data
      analysis methods, which aim to model the blood-oxygen-level-dependent (BOLD)
      response of voxels as a function of time, the theory of power spectrum (PS)
      analysis focuses completely on understanding the dynamic energy change of
      interacting systems. We propose a new convolution PS (CPS) analysis of fMRI data,
      based on the theory of matched filtering, to detect brain functional activation
      for fMRI data. First, convolution signals are computed between the measured fMRI
      signals and the image signal of prior experimental pattern to suppress noise in
      the fMRI data. Then, the PS density analysis of the convolution signal is
      specified as the quantitative analysis energy index of BOLD signal change. The
      data from simulation studies and in vivo fMRI studies, including block-design
      experiments, reveal that the CPS method enables a more effective detection of
      some aspects of brain functional activation, as compared with the canonical PS
      SPM and the support vector machine methods. Our results demonstrate that the CPS
      method is useful as a complementary analysis in revealing brain functional
      information regarding the complex nature of fMRI time series.

PMID- 19758855
TI  - An optically coupled system for quantitative monitoring of MRI-induced RF
      currents into long conductors.
AB  - The currents induced in long conductors such as guidewires by the radio-frequency
      (RF) field in magnetic resonance imaging (MRI) are responsible for potentially
      dangerous heating of surrounding media, such as tissue. This paper presents an
      optically coupled system with the potential to quantitatively measure the RF
      currents induced on these conductors. The system uses a self shielded toroid
      transducer and active circuitry to modulate a high speed light-emitting-diode
      transmitter. Plastic fiber guides the light to a photodiode receiver and
      transimpedance amplifier. System validation included a series of experiments with
      bare wires that compared wire tip heating by fluoroptic thermometers with the RF
      current sensor response. Validations were performed on a custom whole body 64 MHz
      birdcage test platform and on a 1.5 T MRI scanner. With this system, a variety of
      phenomena were demonstrated including cable trap current attenuation, lossy
      dielectric Q-spoiling and even transverse electromagnetic wave node patterns.
      This system should find applications in studies of MRI RF safety for
      interventional devices such as pacemaker leads, and guidewires. In particular,
      variations of this device could potentially act as a realtime safety monitor
      during MRI guided interventions.

PMID- 19758856
TI  - Multiscale model of liver DCE-MRI towards a better understanding of tumor
      complexity.
AB  - The use of quantitative imaging for the characterization of hepatic tumors in
      magnetic resonance imaging (MRI) can improve the diagnosis and therefore the
      treatment of these life-threatening tumors. However, image parameters remain
      difficult to interpret because they result from a mixture of complex processes
      related to pathophysiology and to acquisition. These processes occur at variable
      spatial and temporal scales. We propose a multiscale model of liver dynamic
      contrast-enhanced (DCE) MRI in order to better understand the tumor complexity in
      images. Our design couples a model of the organ (tissue and vasculature) with a
      model of the image acquisition. At the macroscopic scale, vascular trees take a
      prominent place. Regarding the formation of MRI images, we propose a distributed
      model of parenchymal biodistribution of extracellular contrast agents. Model
      parameters can be adapted to simulate the tumor development. The sensitivity of
      the multiscale model of liver DCE-MRI was studied through observations of the
      influence of two physiological parameters involved in carcinogenesis (arterial
      flow and capillary permeability) on its outputs (MRI images at arterial and
      portal phases). Finally, images were simulated for a set of parameters
      corresponding to the five stages of hepatocarcinogenesis (from regenerative
      nodules to poorly differentiated HepatoCellular Carcinoma).

PMID- 19758857
TI  - Segmentation of the optic disc in 3-D OCT scans of the optic nerve head.
AB  - Glaucoma is the second leading ocular disease causing blindness due to gradual
      damage to the optic nerve and resultant visual field loss. Segmentations of the
      optic disc cup and neuroretinal rim can provide important parameters for
      detecting and tracking this disease. The purpose of this study is to describe and
      evaluate a method that can automatically segment the optic disc cup and rim in
      spectral-domain 3-D OCT (SD-OCT) volumes. Four intraretinal surfaces were
      segmented using a fast multiscale 3-D graph search algorithm. After surface
      segmentation, the retina in each 3-D OCT scan was flattened to ensure a
      consistent optic nerve head shape. A set of 15 features, derived from the
      segmented intraretinal surfaces and voxel intensities in the SD-OCT volume, were
      used to train a classifier that can determine which A-scans in the OCT volume
      belong to the background, optic disc cup and rim. Finally, prior knowledge about
      the shapes of the cup and rim was incorporated into the system using a convex
      hull-based approach. Two glaucoma experts annotated the cup and rim area using
      planimetry, and the annotations of the first expert were used as the reference
      standard. A leave-one-subject-out experiment on 27 optic nerve head-centered OCT
      volumes (14 right eye scans and 13 left eye scans from 14 patients) was
      performed. Two different types of classification methods were compared, and
      experimental results showed that the best performing method had an unsigned error
      for the optic disc cup of 2.52+/-0.87 pixels (0.076+/-0.026 mm) and for the
      neuroretinal rim of 2.04+/-0.86 pixels (0.061+/-0.026 mm). The interobserver
      variability as indicated by the unsigned border positioning difference between
      the second expert observer and the reference standard was 2.54+/-1.03 pixels
      (0.076+/-0.031 mm for the optic disc cup and 2.14+/-0.80 pixels (0.064+/-0.024 mm
      for the neuroretinal rim. The unsigned error of the best performing method was
      not significantly different (p > 0.2) from the interobserver variability.

PMID- 19758858
TI  - Data specific spatially varying regularization for multimodal fluorescence
      molecular tomography.
AB  - Fluorescence molecular tomography (FMT) allows in vivo localization and
      quantification of fluorescence biodistributions in whole animals. The ill-posed
      nature of the tomographic reconstruction problem, however, limits the attainable
      resolution. Improvements in resolution and overall imaging performance can be
      achieved by forming image priors from geometric information obtained by a
      secondary anatomical or functional high-resolution imaging modality such as X-ray
      computed tomography or magnetic resonance imaging. A particular challenge in
      using image priors is to avoid the use of assumptions that may bias the solution
      and reduced the accuracy of the inverse problem. This is particularly relevant in
      FMT inversions where there is not an evident link between secondary geometric
      information and the underlying fluorescence biodistribution. We present here a
      new, two step approach to incorporating structural priors into the FMT inverse
      problem. By using the anatomic information to define a low dimensional inverse
      problem, we obtain a solution which we then use to determine the parameters
      defining a spatially varying regularization matrix for the full resolution
      problem. The regularization term is thus customized for each data set and is
      guided by the data rather than depending only on user defined a priori
      assumptions. Results are presented for both simulated and experimental data sets,
      and show significant improvements in image quality as compared to traditional
      regularization techniques.

PMID- 19758859
TI  - Generalized encoding and decoding operators for lattice-based associative
      memories.
AB  - During the 1990s Ritter, introduced a new family of associative memories based on
      lattice algebra instead of linear algebra. These memories provide unlimited
      storage capacity, unlike linear-correlation-based models. The canonical lattice
      based memories, however, are susceptible to noise in the initial input data. In
      this brief, we present novel methods of encoding and decoding lattice-based
      memories using two families of ordered weighted average (OWA) operators. The
      result is a greater robustness to distortion in the initial input data, and a
      greater understanding of the effect of the choice of encoding and decoding
      operators on the behavior of the system, with the tradeoff that the time
      complexity for encoding is increased.

PMID- 19758860
TI  - Automatic histogram threshold using fuzzy measures.
AB  - In this paper, an automatic histogram threshold approach based on a fuzziness
      measure is presented. This work is an improvement of an existing method. Using
      fuzzy logic concepts, the problems involved in finding the minimum of a criterion
      function are avoided. Similarity between gray levels is the key to find an
      optimal threshold. Two initial regions of gray levels, located at the boundaries
      of the histogram, are defined. Then, using an index of fuzziness, a similarity
      process is started to find the threshold point. A significant contrast between
      objects and background is assumed. Previous histogram equalization is used in
      small contrast images. No prior knowledge of the image is required.

PMID- 19758861
TI  - Unequal power allocation for JPEG transmission over MIMO systems.
AB  - With the introduction of multiple transmit and receive antennas in next
      generation wireless systems, real-time image and video communication are expected
      to become quite common, since very high data rates will become available along
      with improved data reliability. New joint transmission and coding schemes that
      explore advantages of multiple antenna systems matched with source statistics are
      expected to be developed. Based on this idea, we present an unequal power
      allocation scheme for transmission of JPEG compressed images over multiple-input
      multiple-output systems employing spatial multiplexing. The JPEG-compressed image
      is divided into different quality layers, and different layers are transmitted
      simultaneously from different transmit antennas using unequal transmit power,
      with a constraint on the total transmit power during any symbol period. Results
      show that our unequal power allocation scheme provides significant image quality
      improvement as compared to different equal power allocations schemes, with the
      peak-signal-to-noise-ratio gain as high as 14 dB at low signal-to-noise-ratios.

PMID- 19758862
TI  - Directional lapped transforms for image coding.
AB  - In this paper, we present the design of directional lapped transforms for image
      coding. A lapped transform, which can be implemented by a prefilter followed by a
      discrete cosine transform (DCT), can be factorized into elementary operators. The
      corresponding directional lapped transform is generated by applying each
      elementary operator along a given direction. The proposed directional lapped
      transforms are not only nonredundant and perfectly reconstructed, but they can
      also provide a basis along an arbitrary direction. These properties, along with
      the advantages of lapped transforms, make the proposed transforms appealing for
      image coding. A block-based directional transform scheme is also presented and
      integrated into HD Phtoto, one of the state-of-the-art image coding systems, to
      verify the effectiveness of the proposed transforms.

PMID- 19758863
TI  - Laplacian Regularized D-optimal Design for active learning and its application to
      image retrieval.
AB  - In increasingly many cases of interest in computer vision and pattern
      recognition, one is often confronted with the situation where data size is very
      large. Usually, the labels are expensive and the challenge is, thus, to determine
      which unlabeled samples would be the most informative (i.e., improve the
      classifier the most) if they were labeled and used as training samples.
      Particularly, we consider the problem of active learning of a regression model in
      the context of experimental design. Classical optimal experimental design
      approaches are based on least square errors over the measured samples only. They
      fail to take into account the unmeasured samples. In this paper, we propose a
      novel active learning algorithm which operates over graphs. Our algorithm is
      based on a graph Laplacian regularized regression model which simultaneously
      minimizes the least square error on the measured samples and preserves the local
      geometrical structure of the data space. By constructing a nearest neighbor
      graph, the geometrical structure of the data space can be described by the graph
      Laplacian. We discuss how results from the field of optimal experimental design
      may be used to guide our selection of a subset of data points, which gives us the
      most amount of information. Experiments demonstrate its superior performance in
      comparison with conventional algorithms.

PMID- 19758864
TI  - Optical flow estimation for a periodic image sequence.
AB  - We propose a temporal modeling approach for determining image motion from a
      sequence of images wherein the inherent motion is periodic over time. To exploit
      the periodic nature of the motion, we use a Fourier harmonic representation to
      model the temporal evolution of the motion field for the entire sequence. We then
      determine the motion field simultaneously for the different image frames by
      estimating the parameters of this representation model, where the model order in
      the Fourier representation serves as a regularization parameter on the temporal
      coherence of the motion field. This approach can take advantage of the statistics
      of all the available data in the image sequence. In our experiments, we tested
      the proposed approach on several motion types at different noise levels,
      including translational motion, convergent/divergent motion, and cardiac motion.
      Our results demonstrate that this approach could lead to more robust estimation
      of the motion field in the presence of strong imaging noise compared to a frame
      by-frame estimation approach.

PMID- 19758865
TI  - Lightweight probabilistic texture retrieval.
AB  - This paper contemplates the framework of probabilistic image retrieval in the
      wavelet domain from a computational point of view. We not only focus on achieving
      high retrieval rates, but also discuss possible performance bottlenecks which
      might prevent practical application. We propose a novel retrieval approach which
      is motivated by previous research work on modeling the marginal distributions of
      wavelet transform coefficients. The building blocks of our work are the dual-tree
      complex wavelet transform and a number of statistical models for the coefficient
      magnitudes. Image similarity measurement is accomplished by using closed-form
      solutions for the Kullback-Leibler divergences between the statistical models. We
      provide an in-depth computational analysis regarding the number of arithmetic
      operations required for similarity measurement and model parameter estimation.
      The experimental retrieval results on a widely used texture image database show
      that we achieve competitive retrieval results at low computational cost.

PMID- 19758866
TI  - A hybrid frame concealment algorithm for H.264/AVC.
AB  - In packet-based video transmissions, packets loss due to channel errors may
      result in the loss of the whole video frame. Recently, many error concealment
      algorithms have been proposed in order to combat channel errors; however, most of
      the existing algorithms can only deal with the loss of macroblocks and are not
      able to conceal the whole missing frame. In order to resolve this problem, in
      this paper, we have proposed a new hybrid motion vector extrapolation (HMVE)
      algorithm to recover the whole missing frame, and it is able to provide more
      accurate estimation for the motion vectors of the missing frame than other
      conventional methods. Simulation results show that it is highly effective and
      significantly outperforms other existing frame recovery methods.

PMID- 19758867
TI  - Unsupervised multiphase segmentation: a phase balancing model.
AB  - Variational models have been studied for image segmentation application since the
      Mumford-Shah functional was introduced in the late 1980s. In this paper, we focus
      on multiphase segmentation with a new regularization term that yields an
      unsupervised segmentation model. We propose a functional that automatically
      chooses a favorable number of phases as it segments the image. The primary
      driving force of the segmentation is the intensity fitting term while a phase
      scale measure complements the regularization term. We propose a fast, yet simple,
      brute-force numerical algorithm and present experimental results showing the
      robustness and stability of the proposed model.

PMID- 19758868
TI  - The history of EuroPCR... and why a new journal?

PMID- 19758869
TI  - Next generation of drug eluting stents'Sirolimus-analogues'.

PMID- 19758870
TI  - The future of cardiac surgery.

PMID- 19758871
TI  - Drug-eluting stents: the equalizers in treatment of bifurcational lesions.

PMID- 19758872
TI  - Treatment of de novo bifurcation lesions: comparison of Sirolimus- and Paclitaxel
      eluting stents.
AB  - OBJECTIVE: Both the sirolimus-(SES) and paclitaxel-eluting (PES) stents have been
      shown to reduce restenosis rates when used in relatively simple lesions. This
      study aimed to evaluate the results of a consecutive series of patients treated
      with drug-eluting stent implantation for de novo bifurcation lesions, and
      compared outcomes with respect to stenting strategy and stent type. PATIENTS:
      From April 2002 to September 2003, all patients at our institution were treated
      with drug-eluting stent implantation. A consecutive series of 144 patients were
      treated for 167 de novo bifurcation lesions with SES, followed by 104 patients
      treated with PES for 113 lesions. RESULTS: Clinical follow-up at 6 months was
      obtained in 99% patients with survival-free of major adverse cardiac events
      (MACE) of 93.7% for SES versus 85.8% for PES, p=0.05. By multivariate analysis,
      factors predictive for MACE were age, diabetes mellitus, previous CABG,
      multivessel disease, treatment for acute myocardial infarction, and treatment
      with PES. Survival-free of target lesion revascularization (TLR) was 95.7% for
      SES versus 86.8% for PES, p=0.01, with stent type being the only independent
      predictor. Technique of stenting was not a predictor of either MACE or TLR.
      CONCLUSIONS: MACE rates for both the SES and PES are low compared with historical
      data of bare metal stents. The most effective techniques for bifurcation stenting
      remain undefined. Our data suggests a higher need for TLR for the PES compared
      with the SES, however further randomized studies are needed to fully evaluate
      both stenting strategy, and any difference between the stents.

PMID- 19758873
TI  - Influence of technical strategies on the outcome of coronary bifurcation
      stenting.
AB  - OBJECTIVES: The purpose of this study was to analyze from a large prospective
      database started in 1996, the immediate and mid term results of coronary
      bifurcation stenting using bare metal stents. BACKGROUND: Stenting of bifurcation
      lesions remains a challenging subset. Various approaches have been advocated and
      no large prospective studies are available on this subject. METHODS: Between 1996
      and 2002, data were prospectively collected on all patients with bifurcation
      lesions treated with coronary stenting in our institution. Seven-month follow-up
      data were obtained in 96.7% of patients and coronary angiogram was performed in
      the presence of clinical or stress test ischemia. The database was analyzed to
      extract uni-variate and multivariate predictors of acute and 7 months adverse
      events. RESULTS: A total of 1,149 patients were included, median age 65 years,
      19% diabetic patients, unstable angina in 37.3% of cases and acute MI 10.5%. The
      target was the LAD-diagonal bifurcation in 53.2% of cases. Angiographic success
      (residual stenosis < 30%) was obtained in 96.3% of cases for the main branch (MB)
      and side branch (SB) 92.9 % (residual stenosis < 50%). The in-hospital MACE rate
      was 4.6 %. At seven months follow-up, a total MACE rate of 18.1% was observed
      including a target vessel revascularization rate of 13.2% and death rate of 1.6%.
      By multivariate analysis, independent predictors of MACE at seven month follow-up
      were unstable angina (OR 5.02 , p = 0.001, 95 % CI : 3.5 - 7.2), type 4 lesion
      (OR 3.31, p = 0.005, 95 % CI : 1.4 - 7.7), a MB < 2.7 mm (OR 1.8, p = 0.024, 95 %
      CI : 1.08 - 3.01), non use of a provisional T stenting strategy for the SB (OR
      0.48, p = 0.006, 95 % CI : 0.40 - 0.86), and SB stenting (OR 1.48, p = 0.035, 95
      % CI : 1.32 - 2.14). CONCLUSION: Provisional T stenting strategy applied to the
      SB is a predictor of favourable outcome after coronary bifurcation stenting using
      bare metal stents. It significantly reduces the rate of MACE as well as the need
      for repeat TVR at 7-month follow-up.

PMID- 19758874
TI  - Relation between the A1166C angiotensin II type 1 receptor gene polymorphism and
      cardiovascular outcomes after myocardial infarction.
AB  - BACKGROUND: The A1166C polymorphism of the angiotensin II type 1 receptor (AT1R)
      gene, which appears to be the main receptor mediating the pleitropic vascular
      effects of angiotensin II in human beings, has been associated with the risk of
      myocardial infarction (MI), the severity of coronary vasoconstriction and the
      occurrence of sudden death. The question therefore arises whether the A1166C
      polymorphism constitutes a hereditary risk factor of survival after an acute
      myocardial infarction. METHODS AND RESULTS: In a large prospective study of 970
      consecutive patients with a recent myocardial infarction the A1166C polymorphism
      was detected using a PCR based protocol. During the follow-up period (median, 2.5
      years), 75 patients died and 62 from cardiovascular causes. The prespecified
      primary and secondary end points considered were total mortality and
      cardiovascular mortality. No differences between AA, AC, and CC groups were
      observed with respect to baseline clinical characteristics. Beyond conventional
      risk factors like age (RR=2.8 [1.6-5.0] 95% CI; p<0.001), hypercholesterolemia
      (RR=2.1 [1.2-3.7] 95% CI; p<0.014) or low left ventricular ejection fraction
      (RR=2.7 [1.5-4.8] 95% CI; p<0.002), the AT1R CC genotype was also identified as a
      strong independent predictor of death after myocardial infarction (RR=3.2 [1.5
      7.0] 95% CI ; p<0.004). After adjustment for mortality causes, the AT1R CC
      genotype was confirmed to be an independent predictor of cardiovascular death
      after myocardial infarction (RR=2.8 [1.2-6.5] 95% CI; p<0.021). CONCLUSIONS: The
      AT1R CC genotype after adjustment is a strong predictor of death in post MI
      patients. This new finding may help to identify high risk post MI patients who
      may benefit from new therapeutic strategies.

PMID- 19758875
TI  - Primary transcatheter closure of postinfarction ventricular septal defects with
      the Amplatzer septal occluder- immediate results and up-to 5 years follow-up.
AB  - AIM: To report the periprocedural and long-term results of using the Amplatzer
      septal occluder for primary closure of post myocardial infarction ventricular
      septal defects. METHODS AND RESULTS: Transcatheter closure was considered in
      patients with significant left-to-right shunting and defect anatomy and location
      thought to be suitable for closure with such a device. From December 1999 until
      February 2005 eleven patients (9 males) aged 52-81 years (mean 67,9) underwent an
      attempted closure. The time from the onset of infarction to the procedure ranged
      between 2 days and 58 weeks (mean 15,4 weeks). There were three patients in an
      acute phase of infarction (three weeks or less). They were in critical condition
      and required inotropic and ventilatory support. Eight patients (all in a chronic
      infarction phase) were hemodynamically stable and in NYHA class III-IV (6
      patients) or class II (2 patients). A successful device implantation occurred in
      all but one patient, in whom a 26 mm occluder pulled through a 16 mm defect on
      day 8 of infarction. An infarct exclusion surgery was successfully performed in
      this patient. In the remaining 10 patients, the defect size ranged 8-21 mm (mean
      14,3), and the devices 11-30 mm (mean 19,3) were implanted. The procedure and
      screening time ranged 134-286 (mean 187,2) and 23-90 minutes (mean 43,6)
      respectively. The successful implantation did not clinically succeed in both
      patients with the acute septal rupture - they died 2 and 15 days after the
      procedure. In the eight patients in whom the procedure was performed late (3,5-56
      weeks) after the infarction onset, the defect was either completely closed or the
      shunt was insignificant, and they improved dramatically. In the most recent
      follow-up from 1 to 62 months (mean 25,5), the patients have been alive and
      feeling well, and in NYHA I or II class. CONCLUSION: Primary transcatheter
      closure of postinfarction ventricular septal defects may be an alternative to
      surgery in patients with suitable anatomy and completed necrosis. In our
      experience, primary transcatheter closure of ventricular septal defects in
      patients who are in the acute phase of infarction does not improve their
      survival.

PMID- 19758876
TI  - Percutaneous closure of patent foramen ovale: head-to-head comparison of two
      different devices.
AB  - Percutaneous closure of patent foramen ovale (PFO) has been proposed as the
      treatment of choice for young high-risk patients who suffered cryptogenic stroke
      and/or peripheral paradoxical embolism. We sought to compare prospectively two
      different devices used for percutaneous PFO closure.Prospective data were
      collected on 40 high risk patients (females: 38%, mean age : 44 +/- 11 years,
      interatrial septal aneurysm >10 mm: 68%) who underwent percutaneous PFO closure
      after cryptogenic stroke (n = 38) or peripheral paradoxical embolism (n = 2).
      Chronologically, 20 patients were first treated by a PFO-Star (Cardia,
      Burnsville, MI) device. Then, 20 other patients received a Starflex occluder
      (NMT, Boston, MA). The primary endpoint was complete PFO closure at 6 months as
      assessed by transthoracic contrast echocardiography. Secondary endpoints were
      major peri- or post procedural complications and clinical recurrence at 1 year
      follow-up.Baseline clinical and anatomical characteristics were comparable for
      both groups. Complete PFO closure was observed in 50% (PFO-Star) and 90%
      (Starflex) of patients (p=0.001) respectively. Major peri-procedural
      complications occurred in the PFO-star group only: right-sided device thrombus (1
      patient) and aorto-right atrial fistula (1 patient). At 1 year follow-up, no
      clinical recurrence occurred.In conclusion, despite the absence of clinical
      recurrence in this high-risk population with presumed paradoxical embolism,
      complete PFO closure at 6 months follow-up was significantly related to the type
      of closure device used.

PMID- 19758877
TI  - Six-month results of a randomized study to evaluate safety and efficacy of a
      Biolimus A9 eluting stent with a biodegradable polymer coating.
AB  - OBJECTIVES: The STEALTH (STent Eluting A9 BioLimus Trial in Humans) trial was the
      first-in-man study to assess the safety and efficacy of the bioabsorbable-polymer
      coated Biolimus A9-eluting BioMATRIX-Stent, as compared to a bare metal stent
      control (S-Stent). METHODS: One hundred twenty patients were enrolled in a
      prospective, 2:1 randomised, double-blind, multi-center clinical study. Patients
      with single de novo coronary lesions received either a Biolimus-eluting stent
      (n=80 patients with 82 lesions) or bare metal control stent (n=40 patients with
      40 lesions). The primary study endpoint was in-lesion late lumen loss at 6 month
      follow-up. RESULTS: The six month in-lesion late loss was significantly reduced
      in the Biolimus-eluting stent group (0.14 +/- 0.45mm) as compared to the control
      (0.40 +/- 0.41mm) (p=0.004). The in-stent late loss was 0.26 +/- 0.43mm in the
      Biolimus-eluting stent group vs. 0.74 +/- 0.45mm in the control (p<0.001). The
      secondary study endpoint of event-free survival at 6-months was similar in both
      groups (96.3% Biolimus group vs. 97.5% control; p=0.72). There was no significant
      difference in target lesion revascularizations due to the low binary restenosis
      rates in both groups (3.9% in Biolimus group vs. 7.7% in control; p=ns).
      CONCLUSIONS: In this first-in-man feasibility trial, the bioabsorbable-polymer
      coated Biolimus A9-eluting stent demonstrated superior efficacy in reducing 6
      month in-stent and in-lesion late loss and percent diameter stenosis, with
      clinical safety similar to bare metal control stents.

PMID- 19758878
TI  - A randomized comparison of a durable polymer Everolimus-eluting stent with a bare
      metal coronary stent: The SPIRIT first trial.
AB  - BACKGROUND: Everolimus is a sirolimus analogue with similar efficacy in animal
      models, and has been previously successfully tested in humans using an erodable
      polymer. METHODS: This first-in-man single blind multi-centre randomized
      controlled trial assessed the safety and efficacy of everolimus eluting from a
      durable polymer on a cobalt chromium stent in patients with de novo native
      coronary artery lesions. Sixty patients were allocated to stent implantation with
      an everolimus-eluting stent (n=28) or an identical bare stent (n=32). Patients
      had either stable, unstable angina or silent ischaemia. Suitable lesions treated
      were single de novo native coronary lesions with 50-99% stenosis and could be
      covered by a 18 mm stent. The primary endpoint was in-stent late loss at 180
      days, analysed on a per treatment basis. The major secondary endpoint was percent
      in-stent volume obstruction (%VO) as measured by intravascular ultrasound (IVUS)
      at 180 days. The clinical secondary endpoint was major adverse cardiac events
      (MACE) at 180 days. RESULTS: At 6 months, (matched pairs angiographic analysis),
      the in-stent late loss, percentage diameter stenosis and percentage of patients
      with binary restenosis were 0.10 mm, 16% and 0% respectively, in the everolimus
      arm (n=23), as compared with 0.87 mm, 39% and 25.9%, respectively in the bare
      stent arm (n=27, p<0.001 for late loss and diameter stenosis, p = 0.01 for
      restenosis). Significantly less neointimal hyperplasia was observed in the
      everolimus group compared to the bare stent group (10 +/- 13 mm3 vs 38 +/- 19
      mm3, p<0.001) and similarly, less volume obstruction (8.0 +/- 10.4% versus 28.1
      +/- 14.0%, p<0.001). A major adverse cardiac event occurred in 2 patients in the
      everolimus arm versus 6 in the bare stent arm. CONCLUSION: Everolimus eluted from
      a durable polymer on a cobalt chromium stent effectively suppresses neointimal
      growth at 6 months compared to an identical bare stent.

PMID- 19758879
TI  - In-laboratory femoral sheath removal after heparin reversal by protamine after
      percutaneous coronary intervention.
AB  - OBJECTIVE: To evaluate the safety of heparin neutralisation by protamine
      immediately after PCI. DESIGN: Retrospective analysis of prospectively registered
      data. SETTING: A Danish mono-centre study. PATIENTS: All angina pectoris patients
      treated with PCI between January 1999 and December 2002. The cohort was divided
      into two groups. Group I (n=1.129 procedures) were patients admitted January 1999
      to December 1999, and group II n=4.193 procedures) were admitted January 1, 2000
      to December 31, 2002. INTERVENTIONS: In group I, the femoral sheath was removed 4
      hours after the PCI procedure. In group II, circulating heparin was neutralised
      by protamine sulphate, and the femoral sheath removed immediately after the
      procedure. MAIN OUTCOME MEASURES: Rates of puncture site complications, stent
      thrombosis, non-fatal myocardial infarction and death during admission. RESULTS:
      The rates of stent thrombosis, non-fatal myocardial infarction and in-hospital
      mortality were similar in the two groups. The rate of puncture site complications
      were 4,7% in group 1 and 2,6% in group 2 (p<0,001). CONCLUSIONS: Circulating
      heparin can be safely neutralised by protamine sulphate immediately after PCI.

PMID- 19758880
TI  - Safety and feasibility of Bivalirudin with either Cypher and Taxus drug-eluting
      stent during percutaneous coronary intervention.
AB  - OBJECTIVE: This open label, prospective, non-comparative trial is the first to
      evaluate the safety and feasibility of bivalirudin (Angiomax(R), the Medicines
      Company, Parsippany, NJ), during PCI with implantation of the sirolimus eluting
      stent (Cypher, Cordis a J & J, Warren, NJ) or the paclitaxel eluting stent
      (Taxus, Boston Scientific, Natick, MA). METHODS: Patients who were referred for
      elective PCI suitable for stent implantation were recruited. Bivalirudin was
      administrated as a bolus of 1.0 mg/kg followed by 2.5 mg/kg/hour infusion for up
      to 4 hours in the first 68 patients. Following REPLACE 2 study, patients were
      treated with a lower dose of bivalirudin (0.75 mg/kg followed by 1.75 mg/kg/hour
      infusion). RESULTS: 111 patients with 139 lesions were included in the study.
      Thirty-one (27.9%) were diabetics, 14 (12.6%) had unstable angina and 79 (66.6%)
      had multivessel disease. Complex lesion morphology was present in 65 (46.7%), in
      stent restenosis in 32 (23%), total occlusion 7 (5%) and bifurcations 22 (15.8%).
      Activated clotting time (ACT) was verified to be therapeutic following
      bivalirudin administration. During the index procedure no patients required
      provisional use of glycoprotein (GP) IIb/IIIa inhibitors. One patient had
      intracoronary thrombosis which resolved after stenting. An additional 2 patients
      had non-Q wave myocardial infarction (MI). No patients died, had major bleeding,
      required transfusions or sustained vascular complications. 1 patient developed
      thrombosis at 4 months with a documented MI. At 6 month follow-up, 3 (2.7%)
      patients died and 12 (10.8%) patients had target lesion revascularization (1 CABG
      and 11 re-PCI). Angiographic follow-up was achieved in 98 patients (89.9%).
      CONCLUSIONS: This study indicates the safety and feasibility of Cypher or Taxus
      stent implantation in conjunction with bivalirudin administration, with no
      elective use of GP IIb/IIIa inhibitors.

PMID- 19758881
TI  - Critical limb ischemia: a global epidemic.A critical analysis of current
      treatment unmasks the clinical and economic costs of CLI.
AB  - BACKGROUND: Multiple reports document the higher costs of primary amputation (PA)
      compared to infrainguinal bypass surgery (IBS). Recent reports document 40-50%
      cost-effectiveness for percutaneous transluminal angioplasty (PTA) compared to
      IBS. The literature suggests appropriate initial treatment for critical limb
      ischemia (CLI) to be IBS = 38%, PTA = 28%, and PA = 16%. The encouraging 6-month
      Laser Angioplasty for Critical Limb Ischemia (LACI) 93% limb salvage rate
      prompted an independent CLI and LACI clinical and economic analysis. METHODS:
      Between 1999-2001 a reference amputation population (RAP) of 417 patients with at
      least one infrainguinal amputation were identified from a 2.5 million patients
      Medicare/insurance dataset. Clinical data and all medical cost claims for 18
      continuous months, 12-month prior and 6-month post-amputation, were analyzed for
      PTA, IBS, and PA treatment pathways. Based on multiple assumptions and the LACI
      phase II results, economic outcomes were used for a LACI pathway analysis
      compared to PTA, IBS and PA pathways by substituting the LACI trial pathway as
      the initial treatment in lieu of the RAP actual treatment. RESULTS: Initial
      treatments for CLI RAP were PA = 67%, IBS = 23%, PTA = 10%; A majority of wound
      complications (80%) and myocardial infarction 7/9 (77.7%), stroke 13/16 (81.2%),
      and death 2/2 (100%) occurred in the PA RAP. Only 35% of the RAP had an ankle
      brachial index (ABI) and only 16% angiography before PA. 227/417 (56%) of the RAP
      had multiple procedures. Average total costs / patient = $31,638 without LACI and
      $25,373 with LACI. Average savings/patient with LACI = $6,265. CONCLUSION: The
      most common current treatments in the US for CLI are still characterized by high
      rates of primary amputations, multiple procedures, and high rates of procedure
      related complications. Despite the limitations and assumptions of this analysis,
      the utilization of a LACI pathway first revascularization treatment strategy may
      provide clinical and economic cost savings in treating patients with CLI.

PMID- 19758882
TI  - Usefulness and clinical impact of a fractional flow reserve and angiographic
      targeted strategy for coronary artery stenting: FROST III, a multicenter
      prospective registry.
AB  - BACKGROUND: Fractional flow reserve (FFR) is correlated with angiographic and
      intravascular ultrasound assessments of stent placement. Post-stenting FFR has
      been described as a good predictor of clinical events after 6 months. OBJECTIVE:
      To evaluate the feasibility and clinical impact of targeting an FFR > 0.95 via
      incremental in-stent inflation pressures. METHODS: In this multicenter
      prospective study, 100 consecutive patients underwent FFR measurement at
      baseline, after balloon predilatation, and after stenting with 4-atm inflation
      pressure increments from 8 to 20 atmospheres. Inflations were stopped when FFR
      increased above 0.95 and angiographic stenosis was less than 20%. RESULTS: FFR >
      0.95 was achieved in 81% of cases; this FFR target was reached at 8 atm in 47% of
      patients, 12 atm in 16 %, 16 atm in 15%, and 20 atm in 3%. Fifty percent of
      patients with adequate angiographic result had an FFR less than 0.95 and needed
      further higher inflations. FFR was correlated with residual stenosis when the
      total procedure was evaluated, and this correlation persisted when in-stent
      inflations alone were considered. Final FFR was significantly correlated with
      anginal status after 6 months. CONCLUSIONS: Angiography guided PCI does not allow
      optimization of FFR. Since optimal post stenting FFR is correlated to better
      anginal status at 6-months, this suggests that FFR guided PCI is required to
      achieve optimal functional results of PCI.

PMID- 19758883
TI  - Microcoil embolization for ablation of septal hypertrophy in hypertrophic
      obstructive cardiomyopathy.
AB  - BACKGROUND: Percutaneous transcatheter occlusion with ethanol injection of septal
      arteries is an efficient treatment procedure of hypertrophic obstructive
      cardiomyopathy (HOCM). The aim of our study is to evaluate the feasibility and
      efficiency of septal artery embolization with microcoils. METHODS: The microcoils
      were delivered through the guide-wire lumen of a 2mm-diameter coaxial balloon
      positioned inside the target vessel as distally as possible. One or more 0.018"
      straight microcoils (Hilal straight coils, Cook, USA) were used for each target
      vessel until complete flow obstruction was noted. The intraventricular pressure
      gradient was measured before, during and after the procedure. Septal branch
      occlusion was finally documented by coronary angiography. RESULTS: We treated 7
      patients (pts) (male: 5 pts; mean age: 48 (10 years). All patients were
      symptomatic (NYHA class 3 or 4). The target vessels were successfully occluded in
      all patients, without complications. Moderate pain was recorded during and after
      the procedure and the CK level increased five- to ten-fold. The pressure gradient
      diminished during the procedure from 72 +/- 21 mm Hg to 30 +/- 15 mm Hg. The
      number of coils delivered ranged from 3 to 7 / patient. The embolized septal
      branches: 1 vessel in 5 patients; 2 vessels in 1 patient; 3 vessels in 1 case.
      After the procedure the pressure gradient, evaluated by transthoracic
      echocardiography, was 34 +/- 16 mm Hg and 42 +/- 12 mm Hg at 3 month-follow-up.
      Clinical improvement was recorded in all patients after the procedure (NYHA class
      1 or 2). Temporary pacing was necessary in 3 patients during and immediately
      after the procedure but no patient needed permanent pacing. CONCLUSIONS:
      Microcoil embolization is an efficient and safe approach for transcatheter
      ablation of septal hypertrophy in HOCM. This technique induced myocardial
      necrosis without the toxic effects of alcohol, reducing the risk of complications
      (permanent pace-maker implantation, ethanol flow to other myocardial regions).

PMID- 19758884
TI  - Long-term clinical outcome after percutaneous transluminal coronary angioplasty
      with provisional stenting.
AB  - OBJECTIVES: This study reports the 9-year clinical outcome of 409 consecutive
      patients, who underwent coronary angioplasty with provisional stenting during the
      years 1995 to 1999 in the University Hospital of Northwestern Greece. BACKGROUND:
      Despite the rapid changes of interventional cardiology, long-term follow-up
      studies are useful for identifying its limitations and indicating future changes.
      METHODS: Baseline characteristics and information on survival, major cardiac
      events and symptoms were retrospectively obtained from medical records or
      telephone contact. Patient survival rates were calculated and predictive factors
      for survival and cardiac events were identified. RESULTS: Follow-up information
      was obtained in 403 patients (98.5%). Three hundred and thirty-one patients (82%)
      were alive with 150 (45%) being symptom free. The cumulative 5- and 9-year
      survival rates were 87% and 78% respectively, and the corresponding survival free
      from major adverse cardiac events was 65% and 55%. Independent factors affecting
      survival were age>65 years, diabetes, hypertension, multivessel disease and
      ejection fraction<50%, while stenting and the indication of acute myocardial
      infarction for intervention influenced independently survival from cardiac death.
      Non-diabetics, aged</=65, with single-vessel disease suffering from unstable or
      stable angina had a survival rate similar to that of the general Greek population
      (survival at 9 years: 92% vs. 93% respectively). CONCLUSIONS: Certain factors
      influence long-term survival after balloon angioplasty with provisional stenting
      and almost half of the patients (45%) experience a further cardiac event during a
      9 year follow-up period.

PMID- 19758885
TI  - Intracoronary thermography: heat generation, transfer and detection.
AB  - Intracoronary thermography is a potential vulnerable plaque detection technique
      of which the development is ongoing. This review discusses the past and present
      status of this technique from a more fundamental perspective, in which heat
      generation, heat transfer and heat detection are considered. Details of the
      presumed heat source, the macrophage clusters in vulnerable, atherosclerotic
      plaques, are discussed, including their increased energy consumption and heat
      production values. Heat transfer by ways of conduction, convection by blood flow
      and radiation are considered in a quantitative way. Ways to detect heat that are
      currently used are discussed and suggestions for improvement as well as for
      utilization of unexplored possibilities are given. This review enables
      interpretation of previously published results and likely also of results to be
      published in the future.

PMID- 19758886
TI  - Initial clinical experience with an IVUS-guided transmembrane puncture device to
      facilitate recanalization of total femoral artery occlusions.
AB  - PURPOSE: Failure to recanalize chronic superficial femoral artery occlusions is
      frequently caused by subintimal passage of the occlusion with inability to re
      enter the true lumen with the guide-wire. The present study details our initial
      experience with the Pioneer crossing device (Medtronic, Menlo Park, CA) to
      facilitate recanalization of total femoral artery occlusions. MATERIAL AND
      METHODS: 25 consecutive patients (18 male, mean age 63 years) whose failed
      recanalization attempts of chronic superficial femoral artery occlusions (mean
      occlusion length 12.7 cm) with standard techniques were re-scheduled for a
      secondary recanalization procedure. The Pioneer crossing device is a 6.2F rapid
      exchange catheter, which tracks over a 0.014"-wire. A 20MHz phased array IVUS
      transducer is integrated into the tip of the catheter allowing visualization of
      the vessel morphology. Using the guidance of the IVUS cross-sectional image
      supported by colour-flow imaging, the true lumen is punctured with an integrated
      24G needle allowing delivery of a second 0.014"-wire. RESULTS: Re-entry into the
      true lumen was successfully accomplished in all cases without complications. In 8
      cases with severe calcification predilatation of the false channel was necessary
      to allow advancement of the Pioneer crossing device. Furthermore, in 7 patients
      with severe calcification multiple puncture attempts were necessary to penetrate
      the dissection membrane. A procedural success (<25% residual stenosis) could be
      achieved in all cases after predilatation and stenting of the occlusion with self
      expanding nitinol stents. CONCLUSION: The Pioneer crossing device is an effective
      and save tool to facilitate true lumen re-entry during recanalization of total
      superficial femoral artery occlusions.

PMID- 19758887
TI  - Introduction and thoughts on the second issue of EuroIntervention.

PMID- 19758889
TI  - The Endeavor Stent System: will it be the new kid on the block?Numero uno, first
      among equals or equal?

PMID- 19758888
TI  - Coin of the realm: do only randomized trials count or is ART okay?

PMID- 19758890
TI  - Blowing against the wind?

PMID- 19758891
TI  - Beyond crossing a chronic total occlusionAre the drug-eluting stents the solution
      for this old problem?

PMID- 19758892
TI  - Launching a new journal dedicated to interventional cardiology is a great
      challenge.Why does it represent such an event?

PMID- 19758893
TI  - Training in interventional cardiology in Europe: how to move from chaos to
      rational common programmes?

PMID- 19758895
TI  - EuroIntervention: a politician's viewEuroPCR 2005 - Palais des Congres - Paris -
      Tuesday 24th May 2005.

PMID- 19758894
TI  - EuroPCR highlights 2005.

PMID- 19758896
TI  - Arterial Revascularisation Therapies Study Part II - Sirolimus-eluting stents for
      the treatment of patients with multivessel de novo coronary artery lesions.
AB  - AIM: To determine the safety and effectiveness of CYPHER(R) sirolimus-eluting
      stent implantation in patients with multivessel disease; and to compare outcomes
      against the historical results of the two arms of the Arterial Revascularisation
      Therapies Study (ARTS I). METHODS AND RESULTS: ARTS II is a 45 center, 607
      patient single arm trial; the1-year outcomes were compared to the historical
      controls of the ARTS I trial, using conventional and Bayesian statistical
      methods. Patients were stratified by clinical site to ensure that at least one
      third had 3-vessel disease to achieve the number of treatable lesions per patient
      comparable to ARTS I. Multivessel stenting was performed with sirolimus-eluting
      stents according to local institutional practice with the goal of achieving
      complete revascularisation. The majority of patients (53.5%) had 3-vessel disease
      and diabetes was present in 26.2%. Mean stented length was 72.5mm, with 3.7
      stents implanted per patient. The 1-year survival rate was 99.0%, the composite
      of death / stroke and MI-free survival was 96.9%, freedom from revascularisation
      was 91.5% and the composite endpoint of MACCE-free survival was 89.5% (the
      primary endpoint). Diabetic patients treated with sirolimus-eluting stents were
      more likely to undergo repeat revascularisation (RR 1.97, 95% CI 1.16 - 3.34) and
      experience a MACCE (RR 1.85, 95% CI 1.16 - 2.97) than non-diabetics at 1-year. In
      the unadjusted comparison with the historical control arms of ARTS-I-CABG and
      ARTS-I-PCI, the respective relative risks (RR) and associated 95% confidence
      intervals (CI) for the endpoints were: (1) freedom from repeat revascularisation
      RR 2.03 (1.23-3.34) and RR 0.44 (0.31-0.61) respectively; and (2) MACCE free
      survival RR 0.89 (0.65-1.23) and RR 0.39 (0.30-0.51) respectively. CONCLUSION:
      The low incidence of MACCE and repeat revascularisation in ARTS II suggests that
      contemporary PCI with sirolimus-eluting stents is safe and efficacious for the
      treatment of multivessel coronary artery disease. Compared to the historical
      population of ARTS I, surgery still afforded a lower need for repeat
      revascularisation although overall MACCE rates in ARTS II approached the surgical
      results and were significantly better than bare stenting in ARTS I.

PMID- 19758897
TI  - First-in-human study of the Endeavor ABT-578-eluting phosphorylcholine
      encapsulated stent system in de novo native coronary artery lesions: Endeavor I
      Trial.
AB  - AIMS: The Endeavor I study was the first clinical study evaluating the safety and
      feasibility of the Endeavor stent system in the treatment of symptomatic coronary
      artery disease. The Endeavor Stent System comprises a new cytostatic,
      antiproliferative and immunosuppressive agent in the same class of drugs as
      sirolimus, (ABT-578), a phosphorylcholine polymer-based coating, and an
      established cobalt-alloy stent with thin struts, (Driver stent). METHODS AND
      RESULTS: One hundred consecutive patients with symptomatic ischemic heart disease
      due to de novo, obstructive lesions of native coronary arteries were treated with
      the Endeavor stent system at eight centers in Australia and New Zealand according
      to contemporary practice. The acute lesion, procedure, and device-deployment
      success rates were all 100%. Independent core laboratories analyzed quantitative
      coronary angiography (QCA) and intravascular ultrasound (IVUS) data immediately
      after stent implantation, and at 4 and 12 month follow-up. At 12 months, in-stent
      late lumen loss was 0.61+/-0.44 mm; in-segment late lumen loss was 0.43+/-0.44
      mm, and neointimal hyperplasia volume was 14.2+/-11.8 mm3 (corresponding to a
      percent volume obstruction of 9.7%+/-8.5%). By QCA and IVUS, the pattern of
      neointimal hyperplasia was greatest within stent and not at the stent edges. The
      binary angiographic restenosis rate (defined as >50% diameter stenosis) at 4 and
      12 months was 2.1% (2/97) and 5.4% (5/93) respectively. The cumulative incidence
      of major adverse cardiac events (MACE, defined as death, myocardial infarction,
      emergent cardiac surgery or repeat revascularization of the index lesion), was 1%
      at 30 days and 2% at 4 and 12 months. CONCLUSION: This 100 patient pilot study
      demonstrates that the Endeavor stent system is a reliable and safe treatment for
      obstructive coronary disease, providing durable event free clinical outcomes to
      12 months by suppression of neointimal proliferation of the target lesion. The
      results support further pivotal evaluation in larger randomized clinical trials.

PMID- 19758898
TI  - One-year clinical outcome of various doses and pharmacokinetic release
      formulations of paclitaxel eluted from an erodable polymer - Insight in the
      Paclitaxel In-Stent Controlled Elution Study (PISCES).
AB  - AIMS: The one year clinical benefit of various doses and release durations of
      paclitaxel eluted from an erodable polymer has not been evaluated so far. METHODS
      AND RESULTS: Conor paclitaxel-eluting stents have intra-stent wells in which drug
      and polymer are deposited. Stents with six different release formulations (dose:
      10 microg or 30 microg, duration: 5, 10 or 30 days, direction: mural or
      bidirectional) were implanted in 6 patient cohorts. Clinical follow-up was
      conducted at 4 and 12 months. Quantitative angiography and IVUS were performed at
      4 months, and additional angiographic and IVUS follow-up were performed for
      groups D5 (10microg/30days/mural) and D6 (30microg/30days/mural), as they had
      shown the most favorable results at 4 months. At one year, the lowest major
      adverse cardiac event rates were observed in the slow release (30 day) group
      (5.1% in D5 and 6.9% in D6). One-year in-stent late loss was 0.52+/-0.34 mm in D5
      and 0.36+/-0.50mm in D6 (p=0.20) while neointimal area was 0.99+/-0.54 mm2 in D5
      and 0.77+/-0.92 mm2 in D6 (p=0.42). Corresponding in-stent binary restenosis at
      one year was 0% and 5.6% respectively (p=0.36). CONCLUSIONS: Patients who
      received the slow release formulation stent had better clinical outcome at one
      year than those who received the fast release formulation. However, the effect on
      neointimal suppression requires investigation in a larger population to determine
      whether the high dose formulation confers an additional clinical benefit.

PMID- 19758899
TI  - Immunosuppressive oral prednisone after percutaneous interventions in patients
      with multi-vessel coronary artery disease. The IMPRESS-2/MVD study.
AB  - AIMS: To assess efficacy and safety of oral treatment with prednisone at
      immunosuppressive dose after percutaneous coronary interventions (PCI) in
      patients with multi-vessel coronary artery disease (CAD). METHODS AND RESULTS:
      Eighty-six consecutive patients with multi-vessel CAD were successfully treated
      with multiple PCI. Forty-three patients (115 coronary stenoses), with C-reactive
      protein >3mg/L 48 hours after PCI and in absence of contra-indications received
      45-day high-dose oral prednisone treatment (study-group). Forty-three patients
      (106 coronary stenoses), did not receive prednisone (control-group). The primary
      clinical endpoint was 12-month event-free survival rate (defined as freedom from
      death, myocardial infarction, and the need for target vessel revascularisation).
      Angiographic restenosis at 8 months was assessed in the study group only. Event
      free survival rates were 93 and 69.8% in the study and the control group,
      respectively (relative risk 0.34, 95%CI: 0.12 to 0.96, p=0.006). Target vessel
      revascularisation rate in the study group was 7% compared to 27.9% in the control
      group (p=0.01). Quantitative coronary angiography performed on 104 lesions of 39
      prednisone-treated patients (91%) showed 4 restenotic lesions (3.8%). The mean
      late lumen loss was 0.61+/-0.35mm and loss index 31.3+/-21.6%. CONCLUSION: Oral
      immunosuppression with prednisone effectively reduces clinical restenosis in
      patients undergoing complex, multi-vessel PCI.

PMID- 19758900
TI  - Drug-eluting stent-supported percutaneous coronary intervention in high risk
      patients refused cardiac surgery.
AB  - AIMS: Randomized trials of drug-eluting stents (DES) have demonstrated their
      ability to improve clinical outcome in relatively simple lesion/patient subsets.
      Their potential in patients for whom the risk of coronary bypass grafting is
      judged prohibitive, remains largely unexplored. To investigate periprocedural and
      one-year outcome of percutaneous coronary intervention (PCI) using DES in
      patients refused for coronary artery bypass grafting (CABG). METHODS AND RESULTS:
      At our institution, the therapeutic approach for all patients with multi-vessel
      disease is decided, by consensus at a conjoint session with the clinical
      cardiologist, interventionalist and cardiothoracic surgeon enabling unequivocal
      identification of patients, refused surgery, who were referred for PCI. The
      EuroSCORE was used to predict peri-operative mortality. From April 2002 to
      December 2003 we identified 84 such patients. The mean age was 70.9+/-10.1 years
      and 68% were men. More than one third had prior CABG. Most patients presented
      with stable or unstable angina pectoris. The reasons for refusal for CABG were:
      unsuitable coronary anatomy (37%), poor functional status (28%), patent grafts
      other than the culprit vessel (25%), prior CABG (28%), severe left ventricular
      dysfunction (13%), co-existing malignancy (18%), prior disabling stroke (12%) and
      morbid obesity (11%). Using the standard and logistic EuroSCORE methods, the
      predicted in-hospital mortality rates were 7.8+/-3.3% and 13.2+/-11.1%
      respectively. In this study, the actual mortality rate was 1.2% at 30 days, 3.6%
      at 6 months and 4.8% at 1 year follow-up. CONCLUSIONS: PCI in high risk patients
      who were refused for CABG in the DES-era resulted in an early and 1-year
      mortality rate that was significantly lower than the predicted operative
      mortality.

PMID- 19758901
TI  - Early and late results of percutaneous revascularization in patients with
      ischemic cardiomyopathy and decreased left ventricular ejection fraction.
      (Revascularisation in Heart Failure Trial, REHEAT Registry).
AB  - AIMS: REvascularization in Ischaemic HEart Failure Trial (REHEAT) is a registry
      prospectively evaluating the outcomes of percutaneous myocardial
      revascularization in postinfarction patients with ischemic cardiomyopathy and
      various categories of surgical risk. METHODS AND RESULTS: One hundred seventy
      consecutive postinfarction patients with LVEF <40% and angiographically
      documented coronary stenoses eligible for PCI were enrolled to the study. The
      study end-points included: angiographic success of PCI, major adverse events at
      30 days and 1 year after procedure, long-term survival, functional status (CCS
      and NYHA class) and LVEF 12 months after the intervention. Angiographic success
      rate was 98,8% and complete revascularization was achieved in 38.8% cases. No
      periprocedural deaths were registered. Thirtieth-days survival was 97% and was
      better in comparison to calculated survival for CABG patients; 1-year survival
      was 94.4% and was not inferior to predicted survival after CABG. In the general
      study population a significant improvement of LVEF (27,8+/-7,0 to 35,9+/-9,4%)
      was shown (absolute change mean 6.45+/-10%). In low/intermediate risk group the
      LVEF increase was lower (6.5+/-10,9) in comparison to high risk group (10,3+/
      9,6%)(p=0,042). In both groups a significant and comparable reduction of angina
      and heart failure severity was shown in 1-year follow-up. CONCLUSION: PCI in
      postinfarction patients with markedly reduced LVEF is associated with a
      significant increase of LVEF and favorable clinical outcome (CCS and NYHA class).
      PCI is safe, feasible and can be an alternative approach to CABG both in
      low/intermediate and high surgical risk patients.

PMID- 19758902
TI  - Drug-eluting stent implantation for chronic total occlusions: comparison between
      the Sirolimus- and Paclitaxel-eluting stent.
AB  - AIMS: Long-term results following percutaneous coronary intervention (PCI) with
      bare metal stents in the treatment of chronic total occlusions (CTOs) is hindered
      by a significant rate of restenosis and re-occlusion. Drug-eluting stents have
      shown dramatically reduced restenosis rates for the treatment of relatively
      simple non-occlusive lesions, though there is only limited data as to the
      efficacy in CTO's. We evaluated the long-term results of the sirolimus-eluting
      stent (SES) and paclitaxel-eluting stent (PES) for the treatment of CTOs. METHODS
      AND RESULTS: From April 2002, all patients at our institution were treated with
      SES as the device of choice during PCI. During the first quarter of 2003 the
      default strategy changed to the use of PES. Drug-eluting stent implantation was
      carried out in CTOs (defined as >3 months' duration) in 9% of de novo PCI
      procedures. A total of 76 consecutive patients were treated with SES
      implantation, followed by a consecutive series of 57 patients treated with PES
      implantation. These patients were compared with a similar group of patients
      (n=26) treated with BMS in the 6-month period preceding April 2002. At 400 days,
      the cumulative survival-free of target vessel revascularization was 80.8% in the
      BMS group versus 97.4% and 96.4% in the SES and PES groups respectively (p=0.01).
      CONCLUSIONS: The use of both the SES and PES in the treatment of chronic total
      coronary occlusions reduces the need for target vessel revascularization compared
      to bare metal stents.

PMID- 19758903
TI  - Primary stenting for left-main shock syndrome.
AB  - AIMS: Acute myocardial infarction (AMI) complicated by unprotected left-main
      shock (LMS) remains a highly morbid event among acute coronary syndromes. Whether
      early percutaneous coronary intervention (PCI) in the stent era improves the
      clinical outcome remains poorly defined. METHOD AND RESULTS: 25 consecutive
      patients who presented with LMS were treated by primary stenting of bare metal
      stents for the unprotected left main lesion with an aid of conventional
      supportive measures. Mean age of the patients was 67 (range, 46-89), 84% were
      male, with an initial mean systolic BP of 88mmHg (range, 40-120), HR of 82 bpm
      (range, 38-130), and symptom onset to reperfusion of 4.8hours (range, 1.5-17). An
      initial TIMI grade 0 flow was noted on the emergent CAG among 56% of the
      patients, but after PTCA and stenting, TIMI grade 3 flow was obtained among 84%.
      30-day mortality was 32%, while one patient underwent emergent CABG for subacute
      stent thrombosis and 3 patients required elective CABG for residual disease
      during admission. Among 11 patients who were discharged alive, one required
      further institutionalization for ischemic brain injury, and the 2 required target
      vessel revascularization for restenoses. The major adverse cardiac events (death,
      re-infarction, stroke, and target vessel revascularization) occurred in 68%
      (17/25) over a 12-month follow-up, including 40% of mortality. CONCLUSIONS: AMI
      complicated by unprotected LMS could be treated effectively with a prompt
      application of stenting and result in an acceptable mortality and morbidity.

PMID- 19758904
TI  - 150 microgram intracoronary adenosine bolus for accurate fractional flow reserve
      assessment of angiographically intermediate coronary stenosis.
AB  - AIMS: Fractional flow reserve measurement is based upon achieving maximum
      hyperemia. A 40 microg intracoronary (IC) adenosine bolus sometimes seems
      insufficient, and we therefore sought to assess the possible role of 100-150
      microg boli in routine. METHODS AND RESULTS: 108 intermediate (49+/-16%) stenoses
      were consecutively studied with 6F catheters. A history of myocardial infarction
      in the territory of the explored artery or myocardial hypertrophy were the
      exclusion criteria. Mean FFR was 0.82+/-0.12 with a 40 microg adenosine bolus and
      decreased to 0.80+/-0.12 and 0.80+/-13 respectively with 100microg and 150 microg
      boli (P<0.001 vs 40microg in both cases; 100 vs 150 microg, NS). The 40 microg
      bolus failed to diagnose 8 out of 30 (27%) significant stenoses (i.e., final FFR
      <0.75). The large boli led to 12 (11%) transient asymptomatic and spontaneously
      resolving AV blocks without other side-effects. CONCLUSION: FFR underestimated a
      quarter of intermediate stenoses with the currently used 40microg IC adenosine
      bolus. A large bolus up to 150 microg appears to be accurate and safe for routine
      FFR measurement.

PMID- 19758905
TI  - Preprocedural creatinine clearance and long term survivalafter successful
      coronary stenting.
AB  - AIM: The clinical outcome of patients with severe renal dysfunction undergoing
      percutaneous coronary intervention (PCI) is poor. However little is known
      concerning the impact of mild renal insufficiency on long-term clinical outcomes
      after successful coronary stenting. The present prospective observational study
      was designed to evaluate long-term clinical outcomes in relation to renal
      insufficiency after successful coronary stenting. METHODS AND RESULTS: A
      consecutive series of 1454 patients were enrolled between January 4th 1997 and
      January 4th 1999 Demographic and clinical characteristics and long term clinical
      outcome were compared for patients with normal creatinine clearance (>60 ml/mn),
      mild renal dysfunction (creatinine clearance rates 30-60 ml/mn) and severe renal
      dysfunction (creatinine clearance rates <30 ml/mn). Patients with moderate or
      severe renal dysfunction were older and with more severe coronary artery disease.
      Beyond conventional risk factors like age (RR = 1.72 [1.10-2.68] 95% CI ;
      p<0.018), or low left ventricular ejection fraction (RR = 2.60 [1.72-3.94] 95% CI
      ; p<0.001), severe (creatinine clearance rates < 30 ml/min) and mild (creatinine
      clearance 30-60 ml/min) renal dysfunction were also identified as strong
      independent predictors of death after successful coronary stenting (RR = 4.91
      [2.63-9.15] 95% CI, p<0.001 and RR = 1.57 [1.03-2.40] 95% CI, p<0.034,
      respectively). CONCLUSIONS: In patients with successful coronary stenting,
      preprocedural creatinine clearance remains an important independent predictor of
      long term death. These data reinforce the importance of widespread application of
      prevention strategies especially in patients with coronary artery disease
      complicated by renal dysfunction.

PMID- 19758906
TI  - CMR assessment of AMI patients treated by PCI shows delays in myocardial
      reperfusion despite initial achievement of TIMI 3 flow.
AB  - AIMS: Cardiovascular magnetic resonance imaging (CMR) perfusion studies performed
      early after successful angioplasty in AMI nearly always shows incomplete tissue
      reperfusion despite normal coronary blood flow by TIMI score. In contrast, when
      performed a few weeks or months after AMI, CMR first-pass perfusion (FP) is
      usually normal. This study was conducted to determine the kinetics of tissue
      reperfusion after reperfused AMI in humans. METHODS AND RESULTS: We prospectively
      analyzed patients who presented with ST-segment elevation myocardial infarction
      between July 2002 and January 2005. Included patients had TIMI 3 flow after acute
      PCI and CMR FP imaging within four months post-MI. CMR FP was performed after
      injection of 20 cc of gadolinium chelate and imaging was performed with a Siemens
      Symphony 1.5 T. For FP analysis, each slice was divided into 8 segments which
      were subdivided into subepicardial and subendocardial layers. Normal perfusion
      was defined as less than 5% of segments involved by hypoperfusion. Patients were
      divided into groups according to the delay between MI/reperfusion and CMR. The
      reperfusion curve was established by plotting the percentage of patients with
      normal perfusion in each subgroup. A total of 184 CMR were analysed out of 146
      patients included in the study. Probability of normal perfusion was 24%, 31%,
      35%, 33% and 43% at respectively day 1, day 2, day 4, day 6 and day 8. This
      probability increased to 67% at week 2, and at week 3 reached a 100% probability
      (Spearman's rho -0.471, p = 0.001). CONCLUSIONS: Despite complete restoration of
      epicardial flow, early myocardial reperfusion as assessed by CMR is very
      uncommon. Myocardial perfusion is progressively restored and capillary blood
      volume recovered normal values between weeks 2 and 4 after MI.

PMID- 19758907
TI  - The SYNTAX Score: an angiographic tool grading the complexity of coronary artery
      disease.

PMID- 19758908
TI  - The effect of variable release kinetics on Paclitaxel efficacy from a drug
      eluting stent in a porcine model.
AB  - AIMS: Paclitaxel is a potent and effective inhibitor of neointimal proliferation
      after coronary stenting. The Conor stent loaded with Paclitaxel can be programmed
      with multi-parameter matrix of dose, temporal release profiles and release
      pathways. The aim of this study was to determine the most efficacious dose and
      release pattern of Paclitaxel in a porcine model and parallels the PISCES trial.
      METHODS: 32 farm pigs were implanted with Conor stents loaded with 10 or 30
      microg of Paclitaxel with, 10 or 30 day and mural or bidirectional release
      patterns. Angiographic and histomorphometric analysis was -performed at 30 and 90
      days. RESULTS: All doses of Paclitaxel were angiographically superior to control
      (P < 0.01). At 30 days, intimal thickness was similar between Pisces D4 (30
      microg/10 days, bidirectional release), D5 (10 microg/30 day mural) and D6 (30
      microg/30 day, mural) with D4 having the lowest intimal thickness (167+/-59
      microm). There was a significant increase in the mural injury associated with D4
      in comparison to all other doses (P < 0.00001). At 90 days D4 was significantly
      worse in comparison to Pisces D5 and D6; (P < 0.01) and Pisces D5 and D6 were
      similar to controls. CONCLUSIONS: 10 day release of Paclitaxel may be too short a
      period to inhibit neointimal proliferation after coronary stenting, or the rapid
      release of Paclitaxel may induce chemical injury causing secondary insult to the
      artery resulting in a rebound increase in intimal thickness at 90 days. These
      data parallel clinical findings in the PISCES trial.

PMID- 19758909
TI  - Inhibition of intimal hyperplasia by the tetracycline derived mmp inhibitor
      doxycycline in vein graft disease in vitro and in vivo.
AB  - AIMS: Intimal hyperplasia, characterised by smooth muscle cell migration and
      proliferation, requires extracellular matrix degradation which is mediated by
      matrix metalloproteinases (MMPs). In this study, the effect of tetracycline
      derived doxycycline, a specific MMP inhibitor of both activity and synthesis, on
      intimal hyperplasia in vitro and in vivo was assessed. METHODS AND RESULTS:
      Segments of human saphenous veins were cultured for 4 weeks in absence or
      presence of doxycycline (10microg/ml) (n=6). A 81% inhibition in intimal
      hyperplasia was observed in the doxycycline treated segments compared to
      controls. To assess the effect of doxycycline on intimal hyperplasia in vivo,
      perivascular cuffs were placed around femoral arteries in mice with or without
      doxycycline in the drinking water (3 mg/ml). In this in vivo model for intimal
      hyperplasia doxycycline significantly reduced (68%, n=6) intimal hyperplasia when
      compared to controls. In addition the effect of doxycycline on vein graft
      thickening was assessed in a murine venous interposition model. In this in vivo
      model vein graft thickening was reduced by 35 % in the doxycycline treated mice
      (3 mg/ml in drinking water). Furthermore, a reduction in vascular MMP expression
      was observed in these mice. CONCLUSION: Treatment with tetracycline derived
      doxycycline results in significant inhibition of intimal hyperplasia in vitro and
      in vivo and may be an effective strategy to prevent post interventional
      restenosis and vein graft disease.

PMID- 19758910
TI  - Assessment of stent dimensions with a novel intracoronary balloon-based system:
      comparative study versus intravascular ultrasound and quantitative coronary
      angiography. The CAMUS - Coronary Angioplasty Metricath vs. UltraSound Trial.
AB  - AIMS: To compare measurements of coronary stent dimensions using a novel, low
      pressure balloon catheter-based technique - Metricath (MC), with those obtained
      by intravascular ultrasound (IVUS) and quantitative coronary angiography (QCA).
      BACKGROUND: Intravascular ultrasound (IVUS), the current gold standard to
      optimize stent placement is expensive, not widely available, and needs expertise
      for interpretation. METHODS AND RESULTS: We compared cross-sectional diameter and
      area measurements obtained by MC, IVUS, and QCA immediately after successful
      stent implantation. The order of measurements was randomized. Both on-line and
      off-line (independent core lab) analysis was performed.Measurements were obtained
      in 21 patients at 22 stents in the LAD (n=10), RCA (n=6), and LCx (n=6). Nominal
      stent diameter was 2.5-3.5 mm. Average stent diameter was 2.54+/-0.28 mm by QCA,
      2.77+/-0.31 mm by IVUS, and 2.86+/-0.28 mm by MC (P<0.001 QCA versus MC, P=0.13
      IVUS versus MC). Results of on-line area measurements showed a small but
      significant difference between IVUS and MC 0.53 mm2, 95% confidence interval 0.17
      0.90 mm2, P<0.01. Regression analysis demonstrated, however, that MC correlated
      best with off-line IVUS (diameter: y=1.01x, R2=0.83, P<0.001; area: y=1.02x,
      R2=0.81, P<0.001). Bland-Altman analysis showed a mean difference in diameter
      between on-line MC and off-line IVUS of 0.03+/-0.12 mm and between MC and off
      line QCA of 0.10+/-0.23 mm. CONCLUSION: MC is a new, promising method providing
      information on average stent dimensions that is equivalent to that obtained by
      off-line IVUS analyzed in an independent core lab.

PMID- 19758911
TI  - Serial assessment of tissue growth inside and outside the stent after
      implantation of drug-eluting stent in clinical trials. - Does delayed neointimal
      growth exist?

PMID- 19758912
TI  - Magnetic wire navigation in PCI:Should magnetism "attract" the
      interventionalist's attention?

PMID- 19758913
TI  - Spirit First - Another hurdle is cleared.

PMID- 19758914
TI  - 2005 Business meeting of the Working Group on Interventional Cardiology.

PMID- 19758915
TI  - One-year results of a durable polymer everolimus-eluting stent in de novo
      coronary narrowings (The SPIRIT FIRST Trial).
AB  - AIM: Short-term results of durable polymer everolimus-eluting stents have shown
      significant improvements in clinical and angiographic outcomes. This report
      presents the 1-year clinical and angiographic data from the SPIRIT FIRST Trial.
      METHODS AND RESULTS: This first-in-man single blind multi-centre randomized
      controlled trial assessed the safety and efficacy of everolimus and a durable
      polymer on a cobalt chromium stent in patients with de novo native coronary
      artery lesions. Of the 60 patients enrolled, a total of 56 patients (27
      everolimus arm and 29 bare stent arm) were qualified to per-treatment analyses at
      1 year. Quantitative angiographic and intravascular ultrasound (IVUS) analyses
      were performed. Angiographic late loss, IVUS neointimal volume obstruction and
      major adverse cardiac events (MACE) at 1 year were assessed as the study
      endpoints. At 1 year, the in-stent late loss and diameter stenosis of patients
      were 0.24 mm and 18% in the everolimus arm (n=20), as compared with 0.84 mm and
      37% in the bare stent arm (n=25, p < 0.001). Significantly less neointimal
      hyperplasia was observed in the everolimus arm compared to the bare stent arm
      (neointimal volume, 13+/-9 mm3 vs. 37+/-17 mm3, p < 0.001; volume obstruction,
      10+/-7% vs. 28+/-12%, p < 0.001). The overall MACE rate was 15.4% in the
      everolimus arm and 21.4% in the bare stent arm. CONCLUSION: The safety and
      efficacy of everolimus-eluting stent with a durable polymer observed at 6 months
      was sustained at 1 year.

PMID- 19758916
TI  - Randomized comparison of deliverability and in-hospital complications in
      implantation of BxSonic(R), Express(R), and Flexmaster(R) coronary stents.
AB  - AIMS: To compare deliverability and in-hospital complications in implantation of
      BxSonic(R), Express(R), and Flexmaster(R) coronary stents in a randomized
      multicenter trial in five Danish interventional centres. METHODS AND RESULTS:
      Patients with planned stenting of at least one stenotic lesion in a native
      coronary artery were included in the study. There were 494 (664) patients
      (treated lesions) in the BxSonic(R), 499 (657) in the Express(R) and 500 (658) in
      the Flexmaster(R) groups. The groups were well matched with regard to age, sex,
      diabetes, smoking, hypercholesterolemia, hypertension, indication for PCI and
      coronary artery lesion complexity. The study stents were implanted with or
      without predilatation according to ordinary -clinical practice.Rates of
      successful stent implantation and in-hospital stent thrombosis, re-intervention,
      non-fatal myocardial infarction or death. The BxSonic(R), Express(R) and
      Flexmaster(R) stents were successfully implanted in 92,2%, 89,3% and 91,6% of all
      lesions (ns). There were no in-hospital deaths and the rates of in-hospital
      complications were similar in the three stent groups. CONCLUSION: We found
      similar deliverability and in-hospital complication rates of the BxSonic(R),
      Express(R) and Flexmaster(R) stents.

PMID- 19758917
TI  - One year effectiveness of BiodivYsio dexamethazone-eluting stent compared to
      BiodivYsio stent implantation in the treatment of single vessel coronary artery
      disease.
AB  - OBJECTIVE: To investigate the impact of BiodivYsio dexamethazone-eluting stent
      versus BiodivYsio stent on the 12-month outcomes after revascularisation of
      patients with single vessel coronary artery disease. METHODS: From March 2003 to
      February 2004, 102 patients with non-ST elevation acute coronary syndromes,
      angina or silent ischemia after recent ST elevation myocardial infarction (<1
      month) or stable angina pectoris, and single-vessel coronary artery disease were
      treated solely with dexamethazone-eluting stent implantation in our institution.
      Patients were followed up prospectively for twelve months. We compared their
      outcomes to a control group with similar clinical and angiographic
      characteristics of 160 patients treated solely with BiodivYsio stents in the
      preceding study enrolment period (January 2002 to March 2003). RESULTS:
      Approximately 85% of the patients in both groups were treated after an acute
      coronary syndrome. At 12 months, the major adverse cardiac events rates (death or
      non-fatal myocardial infarction or target lesion revascularization) were similar
      in the 2 groups (10.8% in the dexamethazone-eluting and 11.3% in the BiodivYsio
      group, p=1.00). No difference was found in the individual rates of death, non
      fatal myocardial infarction and target lesion revascularization between the 2
      groups. CONCLUSIONS: We conclude that utilization of dexamethazone-eluting stents
      has no effect in reducing the incidence of major adverse cardiac events after 12
      months, as compared with BiodivYsio stent implantation in the treatment of single
      vessel coronary artery disease.

PMID- 19758918
TI  - First-in-man prospective evaluation of temporal changes in coronary plaque
      composition by in vivo intravascular ultrasound radiofrequency data analysis: an
      Integrated Biomarker and Imaging Study (IBIS) substudy.
AB  - BACKGROUND: The composition of atherosclerotic coronary plaque is a major
      determinant of future clinical events. Spectral analysis of IVUS radiofrequency
      data has demonstrated potential to provide detailed quantitative information on
      plaque composition. We prospectively assessed plaque composition in matched
      coronary segments at a six-month interval and sought to explore correlations
      between temporal changes in plaque composition and circulating biomarkers.
      METHODS AND RESULTS: Twenty coronary segments (mean baseline length, 29.9+/
      14.1mm) with non-significant angiographic (<50 % diameter) stenosis, in non
      culprit vessels of patients (n=20) referred for percutaneous intervention, were
      studied at baseline and six-month follow-up. Spectral analysis of IVUS
      radiofrequency data, obtained with a 30 MHz catheter in segments matched on
      predefined anatomic landmarks, was performed with IVUS-Virtual Histology
      software. After 6 months, an overall decrease in the level of different
      biomarkers of instability was present. There were no significant changes in
      absolute values (mm2) of plaque components; calcium (0.036+/-0.05 vs. 0.033+/
      0.04), fibrous (2.68+/-1.5 vs. 2.90+/-1.5), fibrolipidic (0.77+/-0.4 vs. 0.73+/
      0.4), and lipid core (0.42+/-0.4 vs. 0.52+/-0.5), between baseline and six
      months. Nor did any conventional IVUS variable (lumen, vessel, or plaque cross
      sectional area, or percent area stenosis). Change in lipid core area (r=0.51,
      p=0.024), fibrous area (r=0.49, p=0.033) and calcium area (r=0.63, p=0.004), were
      significantly correlated with change in Lp-PLA2 activity. CONCLUSIONS: Routine
      medical care does not result in significant overall changes in IVUS-derived
      plaque size or composition over a 6-month period. This study provides indication
      of quantifiable boundaries beyond which modifications in tissue composition might
      be interpreted as statistically significant.

PMID- 19758919
TI  - Carotid angioplasty and stenting: lesion related treatment strategies.
AB  - AIMS: To evaluate the feasibility of lesion related treatment strategies in
      patients treated for severe carotid artery disease with angioplasty and stenting
      (CAS) under embolic protection devices (EPD). METHODS AND RESULTS: From December
      2001 to August 2004 a total of 377 consecutive patients were enrolled to undergo
      CAS. The procedure was conducted by using several types of stents (cobalt-alloy
      frame, nitinol frame) and of EPD (filter-wires, proximal endovascular clamping
      devices) applied to specific lesions and/or anatomies.Primary endpoint was to
      assess the death and stroke rate at discharge.Secondary endpoints were to test
      the feasibility and safety of tailored CAS (angiographic success, any 
      complication between discharge and 30 days, death of any cause at 30 days).The
      procedural success was achieved in 377/377 patients (100%).Adverse events
      included:1. during procedure: 2 TIAs (0.53%)2. at discharge: 1 death procedure
      related (0.27%), 1 major stroke (0.27%), 2 minor strokes (0.53%), 4 TIAs (1.06%),
      1 intracranial hemorrhage (0.27%); all adverse event rate at discharge 2.92%; all
      strokes and death rate at discharge 1.06%;3. at 30 day f.u.: one death not
      procedure related (0.27%), 1 minor stroke (0.27%);4. overall procedure related
      stroke and death rate: 1.33%. CONCLUSIONS: Our data suggest that using new
      materials/devices matched to specific lesions or anatomies is safe and effective.

PMID- 19758920
TI  - Treatment planning in patients with PAOD:Comparison of CE-MRA employing a
      dedicated peripheral MRA coil and high dose single volume contrast material
      application with i.a. DSA.
AB  - AIM: To evaluate whether contrast enhanced MRA (CE-MRA), including a dedicated
      MRA coil and a high dose of contrast material, correlates to i.a. digital
      subtraction angiography (DSA) when used for treatment planning in patients with
      peripheral arterial obstructive disease (PAOD). METHODS AND RESULTS: A
      retrospective CE-MRA and i.a. DSA comparison was used to evaluate 2200 vessel
      segments with stenosis or occlusion in the pelvic or lower extremity arteries in
      100 patients. A 1.5T MR unit (Magnetom Symphony Quantum, Siemens) employing a
      peripheral angiography array surface coil and automatic table movement was used.
      The interventional approach was planned according to both CE-MRA and DSA
      findings. Visual material was blinded and reviewed by two experienced
      radiologists.In 98.95% (Observer 1) and 98.1% (Observer 2) CE-MRA revealed an
      exact correlation of the grade as well as length of stenosis compared to DSA. The
      sensitivity was 100% and 95.3% for observers 1 and 2 and its specificity 98.3%
      and 100%, respectively. The interobserver agreement between was 0.98 and 0.96 for
      observers 1 and 2, respectively. Suggested treatment and interventional approach
      based on the CE-MRA findings corresponded to DSA in 97%. CONCLUSION: CE-MRA is an
      excellent modality for treatment planning in patients with PAOD. Especially in
      patients with restenosis or reocclusion, CE-MRA enables an accurate, non-invasive
      diagnosis and facilitates treatment planning.

PMID- 19758921
TI  - Local intra-renal fenoldopam infusion causes greater increases in renal artery
      flow velocity than systemic intravenous fenoldopam infusion: a pilot study.
AB  - AIM: Typical intravenous fenoldopam doses result in only minimal increases in
      renal blood flow and glomerular filtration, while higher doses are associated
      with systemic hypotension. We hypothesized that local infusion of fenoldopam into
      the renal arteries would enhance renal perfusion with reduction of arterial
      hypotension. METHODS AND RESULTS: Of 20 patients with renal impairment undergoing
      coronary intervention, 10 received infusion of fenoldopam into the left renal
      artery (IR). Doses were increased progressively (0.1,0.2,0.4 mcg/kg/min) at 5 min
      intervals, separated by a 10 min "wash out" period without drug application.
      Average and maximum peak renal blood flow velocities (APV and MPV) were measured
      using a flow-wire. A comparison group of 10 patients received renal flow
      measurements during IV fenoldopam application using the same escalating dose
      protocol without a drug-free period.The average peak flow velocity increased from
      29.9+/-10.7 cm/s in the IR group and 25.9+/-7.7 cm/s in the IV group at baseline
      (p=ns) to 50.0+/-13.1 cm/s (IR) versus 31.0+/-11.9 cm/s (IV) at the maximum dose
      level (p=0.011). There was a trend towards attenuated reduction of the systemic
      pressure in the IR group compared to the IV group. CONCLUSION: In patients with
      renal insufficiency, local renal infusion of fenoldopam resulted in an
      approximately 50% increase in renal artery velocities without substantial blood
      pressure reduction compared to IV fenoldopam.

PMID- 19758922
TI  - Time-to-reperfusion therapy influences outcome of patients with myocardial
      infarction subjected to facilitated PCI.
AB  - AIM: The purpose of this study was to evaluate the impact of time-to-reperfusion
      on outcome after facilitated percutaneous coronary intervention (PCI) i.e. PCI
      following early pharmacological reperfusion therapy in ST-segment elevation
      myocardial infarction (STEMI). METHODS AND RESULTS: The study population
      consisted of 262 consecutive patients with STEMI, aged <75 years, without
      cardiogenic shock, presenting <12 hours of chest pain onset, transferred from
      community hospitals to a catheterization laboratory with time delay >90 min after
      pharmacological reperfusion therapy (alteplase i.v. bolus 15 mg followed by an
      infusion - 35 mg/60 min; abciximab i.v. bolus 0.25 mg/kg followed by a 12-hour
      infusion - 0.125 microg/kg/min; unfractionated heparin i.v. bolus 40 U/kg
      [maximum 3000 U]). One hundred seventeen patients (44.7%) received
      pharmacological reperfusion therapy <3 h after chest pain onset, 101 (38.5%) at 3
      6 h and 44 patients (16.8%) >6 h. Patent infarct-related artery rates at initial
      angiography were similar among the study groups. PCI significantly improved
      epicardial flow in all three groups. Mortality at 12 months was significantly
      related to time-to-pharmacological reperfusion (3.4% [<3 h], 4.0% [3-6 h], 13.6%
      [>6 h], p = 0.027). At 6 months left ventricular ejection fraction was
      significantly improved in the two groups of patients with time-to-pharmacological
      reperfusion <6 hours and the time-to-pharmacological reperfusion was the
      independent predictor of lack of left ventricular ejection fraction recovery.
      CONCLUSION: Our study shows that among STEMI patients undergoing facilitated PCI,
      time-to-pharmacological reperfusion significantly affects left ventricular
      function recovery and long-term mortality.

PMID- 19758923
TI  - Effect of early statin and selective cyclooxygenase-2 inhibitor therapy on C
      reactive protein level after percutaneous coronary angioplasty in unstable
      angina.
AB  - AIMS: We evaluated the effect of cyclooxygenase-2 inhibitor rofecoxib added to
      atorvastatin, initiated immediately after percutaneous coronary angioplasty
      (PCI), on C-reactive protein (CRP) and interleukin-6 (IL-6) in patients with
      unstable angina (UA). METHODS AND RESULTS: Sixty patients were prospectively
      randomized to receive: (A) 10 mg atorvastatin or (B) 40mg atorvastatin or (C)
      atorvastatin 40 mg plus rofecoxib 12.5 mg. Treatment was continued for 6 months.
      CRP and IL-6 levels increased within 48 hours after PCI in all groups, in
      comparison with A and B, a more pronounced decrease in CRP (mg/l) and IL-6
      (pg/ml) levels at 3- and 6-month follow-up was present in C: CRP at 6 months:
      0.76 vs. 1.92 vs. 0.11, p<0.05; IL-6 at 6 months: 0.02 vs. 0.04 vs. 0.01, p<0.05.
      At 6-month follow-up the reduction in CRP level occurred in 70% of subjects with
      CRP higher than median (3.6mg/l) at baseline vs. 15% of patients with CRP lower
      than median (p<0.041). CONCLUSION: After PCI in UA, cyclooxygenase-2 inhibitor
      rofecoxib added to atorvastatin reduced CRP and IL-6 levels more profoundly than
      atorvastatin alone at 3- and 6-month after intervention. In the group receiving
      combined therapy, reduction in CRP levels was more frequently observed in
      patients with higher CRP at baseline.

PMID- 19758924
TI  - Magnetic navigation in a coronary phantom: experimental results.
AB  - OBJECTIVE: The objective was to investigate the efficacy of a magnetic navigation
      system (MNS) in a coronary phantom. BACKGROUND: The number of coronary
      interventional procedures performed is steadily increasing with the availability
      of new devices to treat more complex lesions. Vessel tortuosity remains an
      important limiting factor in percutaneous coronary intervention. MATERIAL AND
      METHODS: The MNS can orient the tip of magnetized wire. The coronary phantom is a
      representation of the coronary tree. Two operators using both a magnetic wire and
      a standard wire, measured the procedural time (PT), the fluoroscopic time (FT)
      and the radiation exposure/area product (DAP) required to navigate through to
      fourteen segments. Ten wire advancements were performed per segment. RESULTS: In
      all but two segments, the PT was significantly longer using magnetic navigation
      than using manual navigation. The median FT in the left main artery (LMA) - first
      septal segment was 7 seconds vs. 18 seconds, with magnetic and manual navigation
      respectively, (p=0.05); in the LMA - obtuse marginal segment the median FT was 15
      seconds with magnetic navigation vs. 29.5 seconds with manual navigation,
      (p=0.01); in the segment from proximal right coronary artery (RCA1) to the acute
      marginal branch, the median FT was 8 seconds with magnetic vs. 11 seconds with
      manual navigation, (p=0.05); and in the RCA1 -posterior descending segment the
      median FT was 9.5 seconds with magnetic vs. 15 seconds with manual navigation,
      (p=0.006). CONCLUSION: The MNS facilitates wire access to distal segments in a
      coronary phantom, with a reduction in FT and radiation exposure using magnetic
      navigation in tortuous segments.

PMID- 19758925
TI  - Feasibility and safety of guidewire navigation using a magnetic navigation system
      in coronary artery stenoses.
AB  - AIM: Few studies are available on magnetic navigation system (MNS) for coronary
      artery disease. The present investigation was conducted to evaluate the
      feasibility and safety of guidewire navigation with a MNS in diseased coronary
      arteries. METHODS AND RESULTS: Between February 2004 and August 2005, a total of
      59 patients (68 target vessels) underwent magnetic-assisted guidewire navigation
      in coronary arteries with stenoses amenable to coronary intervention. Patients
      were excluded if any of the following conditions applied: pacemakers or
      cardioverter defibrillator implanted; acute myocardial infarction; thrombotic
      lesions; chronic total occlusion; claustrophobia; and renal dysfunction with
      serum creatinine > 2.5mg/dl. Procedural success was defined as successful
      guidewire passage distal to the stenoses with no procedural events, defined as
      either perforation or dissection. Magnetic guidewires successfully crossed 60
      (88%) lesions. Only 1 patient experienced a minor dissection of vessel wall in a
      circumflex lesion and was treated with a coronary stent. There was no other
      complication related to the magnetic guidewire. Nineteen (27.3%) coronary
      interventions were performed with magnetic guidewires. In 4 complex lesions (a
      lesion located in saphenous vein graft with proximal severe tortuosity; 3
      approaches to stent-jailed side branch), where conventional wires failed to cross
      the culprit lesions, magnetic navigation achieved successful guidewire passage.
      CONCLUSIONS: Guidewire navigation using a MNS was feasible and safe. In the four
      complex cases, magnetic navigation enabled crossing of lesions in which
      conventional attempts failed. Further studies are needed to better evaluate the
      efficacy of MNS compared with conventional manual navigation.

PMID- 19758926
TI  - Use of the novel magnetic navigation system Niobe in percutaneous coronary
      interventions; the Hamburg experience.
AB  - INTRODUCTION: In interventional cardiology an increasing demand to treat complex
      coronary lesions (i.e. distal lesions, tortuous vessels, chronic occlusions) has
      developed within the last years. New devices to fulfill this demand are therefore
      needed. METHODS AND RESULTS: The magnetic navigation system (Niobe System;
      Stereotaxis Inc.) represents a novel system which allows 3-dimensional control of
      the guide wire tip using magnetic fields. Two computer controlled permanent
      magnets on each side of the patient create a uniform magnetic field which can
      freely be directed. A small magnet at the guide wire tip will align according to
      the vector of the magnetic field. Advancing and retracting of the wire is to be
      done manually. The remaining steps of angioplasty (i.e. balloon angioplasty and
      stent implantation) are performed conventionally, after magnetically guided
      crossing of the target lesion.The study was performed to proof the feasibility of
      the technique in the treatment of coronary lesions. Seventy seven patients with
      82 coronary lesions underwent magnetic guided coronary interventions. Sixty three
      lesions (77%) could be crossed successfully using magnetic guidance, 13 more by
      switching to conventional guide wires. Successful angioplasty (with or without
      stent implantation) was achieved in 74 lesions (90%). Mean fluoroscopy time was
      13,9+/-8 min. CONCLUSIONS: The use of magnetic guidance in coronary interventions
      is a promising tool to treat complex coronary lesions. With more experience and
      improved devices (i.e. coated wires, steerable microcatheters) the safety and
      efficacy of the procedures should be improved.

PMID- 19758927
TI  - Concept, design and pre-clinical studies for remote control percutaneous coronary
      interventions.
AB  - INTRODUCTION: Percutaneous Coronary Interventions (PCI) is conducted manually
      with the operator standing at the bed side, exposed to continuous X-ray
      radiation. A system where the operator can remotely navigate the wire and device
      during PCI may improve operator safety and convenience and can possibly enhance
      procedural precision. AIM: To develop a remote navigation system (RNS) that will
      allow computer controlled, remote manipulation of percutaneous coronary
      interventions.. METHODS AND RESULTS: The remote navigation system (RNS) is
      designed to handle both coronary guide wire and balloon / stent delivery system
      and can be loaded either with the coronary wire or with both wire and device in
      parallel. The RNS is comprised of a bedside unit and a remote manipulation unit.
      The bed side unit has individual wire and device manipulators, capable of precise
      maneuvering and positioning of the wires and devices. The system was tested in a
      wire glass model and was evaluated in a normal coronary sheep model. The wire
      glass model experiments showed that the wire could be navigated to the required
      branch and the stent/ balloon adequately positioned, as required. The animal
      experiments showed that the wire could access any required coronary branch and
      the stent could be adequately positioned under x-ray fluoroscopy, without causing
      dissection or other vessel trauma. CONCLUSION: A system that enables remote
      control percutaneous coronary procedures was developed and tested in vitro and in
      vivo models. Preclinical studies have demonstrated the feasibility of the concept
      of remote control PCI and have provided the basis for the pilot clinical study of
      remote control, stent-assisted PCI.

PMID- 19758928
TI  - Percutaneous Transvenous Mitral Annuloplasty (PTMA) with the Viking device
      reduces pacing-induced mitral regurgitation.
AB  - OBJECTIVES: The new percutaneous mitral annuloplasty Viking device was evaluated
      in surviving sheep with pacing-induced mitral regurgitation. METHODS AND RESULTS:
      Twenty sheep were subjected to rapid ventricular pacing for one to three months,
      leading to cardiomyopathy and mitral regurgitation. Device implantation could be
      successfully performed in 11 of these animals after pacemaker treatment for 64+/
      7 days. The device-related procedure time was 12+/-2 min. The mean follow-up time
      was 58+/-8 days after implantation of the device. Mitral annulus septo-lateral
      diameter was significantly reduced after insertion of the device, from 35+/-1 mm
      before implantation to 30+/-1 mm at the final follow up intracardiac
      echocardiography (P = 0.0097). The degree of mitral regurgitation (on a scale
      from 0 to 4) was 2.6+/-0.2 before device implantation and decreased to 0.8+/-0.2
      after treatment (P = 0.0039), and the vena contracta was reduced from 7+/-0.4 mm
      to 3+/-0.8 mm (P = 0.0019). Angiography showed no signs of impairment of the
      coronary arteries. No thrombosis was observed. CONCLUSIONS: These results
      indicate that the septo-lateral diameter of the mitral annulus, and the degree of
      experimentally induced mitral regurgitation, can be significantly reduced with a
      percutaneous catheter technique in surviving sheep.

PMID- 19758929
TI  - Adjunctive Antiplatelet / Antithrombotic therapy in percutaneous coronary
      intervention.
AB  - Antiplatelet and antithrombotic treatment is successful in minimising acute and
      subacute stent thrombosis as well as reducing recurrent cardiac events and
      mortality in PCI. In this review we explore the evidence for different treatment
      strategies.Aspirin and clopidogrel together with heparin at the time of the
      procedure are now well established. Glycoprotein (GP) IIb/IIIa blockers have been
      shown to reduce events in high risk patients. However, their routine use has been
      questioned in recent studies.Clopidogrel 600 mg given at least 2 hours
      preprocedure negates the need for additional routine GP IIb/IIIa blockade in
      elective, even diabetic patients. Bivalirudin is equivalent to the routine use of
      GP IIb/IIIa blockade in both elective and ACS patients. Replacing routine GP
      IIb/IIIa blockade in these patients would be significantly cost saving, reduce
      bleeding complications and facilitate rapid discharge policies. However, these
      studies do not have the patient selection to advocate the wholesale replacement
      of GP IIb/IIIa blockade since high risk patients were excluded. Furthermore, with
      the advent of drug eluting stents, progressively more complex lesions are being
      treated that are underrepresented in these trials. Therefore, there still remains
      a rational for continuing to use GP IIb/IIIa blockade in high risk subsets of
      both elective and ACS patients. These subsets are yet to be defined. In the
      setting of primary PCI clear benefits have been shown for the use of adjunctive
      abciximab, with the greatest benefits seen for upfront treatment. Future studies
      will test combinations of GP IIb/IIIa blockade and thrombolytic treatment in
      these patients.

PMID- 19758930
TI  - Percutaneous septal ablation in hypertrophic obstructive cardiomyopathy: current
      status.
AB  - This article reviews aetiology, natural history, and current treatment options in
      hypertrophic cardiomyopathy with a special focus on percutaneous septal ablation,
      which has evolved as an alternative to myectomy in patients with outflow
      obstruction and symptoms refractory to medical treatment. Literature data and the
      own series of 382 interventions (in-hospital mortality and pacemaker implantation
      rates: 1.2% and 7%, respectively) are discussed. Overall satisfactory clinical
      results were seen in about 90% of the patients treated with septal ablation.

PMID- 19758931
TI  - Detection of a necrotic core-rich, highly deformable plaque in an
      angiographically non-diseased proximal LAD.

PMID- 19758932
TI  - Medicine in Europe: proudly forging our own unique identity.

PMID- 19758933
TI  - Retrograde approach for chronic total occlusion: present status and prospects.

PMID- 19758934
TI  - Chronic total occlusions (CTO): the paradox of "premature balloon support".

PMID- 19758935
TI  - EAPCI: update on subspecialty accreditation in Europe.

PMID- 19758936
TI  - Retrograde approach to coronary chronic total occlusions: preliminary single
      European centre experience.
AB  - AIMS: The retrograde approach via septal or epicardial collaterals holds promise
      in improving the success rate of chronic total occlusion (CTO) recanalisation but
      is still viewed as an esoteric practice reserved to a selected group of operators
      using materials not available in Western countries. We sought to introduce the
      novel technique of retrograde CTO recanalisation to our institution using
      materials and resources available outside Japan. METHODS AND RESULTS: Between
      April 2005 and 2007, all patients with a failed antegrade attempt at CTO
      recanalisation were considered and selected based on their appropriateness to
      have a retrograde procedure. Seventeen patients were included. Average age was
      65.3 years. The mean occlusion duration was 33.3 months. Successful CTO
      recanalisation was achieved in 15 of 17 (88.2%) patients. A retrograde wire was
      successfully advanced into the distal occluded vessel and facilitated successful
      CTO recanalisation in 13 (76.5%) patients. Final retrograde wire crossing was
      achieved in seven cases, while in the remaining cases, the CART technique (n=4)
      and 'knuckle' technique (n=2) were successful. In two cases (11.8%), the
      retrograde wire did not reach the distal occlusion because of septal tortuosity
      but a repeat antegrade attempt, aided by contralateral visualisation, was
      successful. In two (11.8%) patients, the procedure was unsuccessful. Cardiac
      magnetic resonance imaging performed in five of the successfully treated
      retrograde cases (45.5%) showed variable degrees of fibrosis in the territory of
      the occluded artery with no significant change after the procedure with the
      exception of one case of contained contrast extravasation within the septum.
      CONCLUSIONS: The novel method of retrograde recanalisation of CTOs was performed
      with a high procedural success in this series and was applicable in 37.1% of
      previously failed antegrade procedures. This technique can also be successfully
      employed despite newly created dissections immediately following a failed
      antegrade attempt.

PMID- 19758937
TI  - Contemporary treatment of patients with chronic total occlusion: critical
      appraisal of different state-of-the-art techniques and devices.
AB  - AIMS: To describe the contemporary approach of chronic total occlusion (CTO)
      treatment of patients at the Thoraxcenter, Rotterdam, The Netherlands.
      Additionally, to make a critical appraisal of the performance of state-of-the-art
      CTO dedicated guidewires and devices in a prospective registry of patients.
      METHODS AND RESULTS: During 20 months, a total of 160 consecutive patients (165
      CTOs) were enrolled. The mean age was 61.5+/-11.1 years and 83.6% were male. In
      91.5% of the patients this was the first attempt to open the CTO and 93.8% were
      de novo. The overall success rate was 60.6%. A median of 1 guiding catheter was
      used per case (Range: 1 to 9) and a median of 4 guidewires (Range: 1 to 11; 13
      different types). 74.5% patients required more than one guidewire/device for the
      treatment of the CTO. The guidewires that most frequently crossed the CTO were
      the following: PT Graphix intermediate 33.0%, Miracle 3 g 27.4% and Crosswire NT
      25.5%. The only device tested as a first option for the treatment of the CTOs was
      the CROSSER. Overall, the CROSSER system was used in 23 (13.9%) patients with a
      success rate of 60.9%. The Point 9(R) X-80 Laser catheter was used in 10 (6.1%)
      patients with a success rate of 60%. Another 3 patients were treated with the
      Point 7(R) laser catheter. Both were used either to facilitate the crossing of
      the balloon, or to treat primarily in-stent restenosis occlusions. The
      SafeCross(R) System was used in 15 (9.1%) patients and the success rate in these
      patients was 46.7%. The most common strategy used in this registry was the use of
      an over-the-wire balloon in 81.5% of the cases. The parallel wire technique was
      used in 27.3% of the cases and in 12.7% was converted into a "see-saw" technique.
      When a large false lumen was created, re-entry into the true lumen was attempted
      in 21.2% of the cases, by means of IVUS guided approach and/or the use of stiffer
      guidewires, such as a Confianza guidewire. Retrograde recanalisation was
      attempted in 10 cases (6.1%), in three cases a graft was used; the remaining
      cases were treated either via collaterals or the septal branches. CONCLUSIONS:
      The treatment of CTOs requires the use of a high number of guiding catheters and
      guidewires, as well as the use of sophisticated devices. The procedure must be
      carefully planned in advance as far as possible, as well as considering a prompt
      change in approach during the performance of the procedure to prevent
      complications derived from long procedures by using specific techniques such as
      parallel wire, see-saw, anchoring balloon, etc.

PMID- 19758938
TI  - Small coronary arteries treated with sirolimus-eluting stents: one-year results
      of the PORTO multicentre registry.
AB  - AIMS: To assess the effectiveness and safety of sirolimus-eluting stents (SES) in
      de novo native coronary lesions in small vessels (</= 2.5 mm). METHODS AND
      RESULTS: PORTO was a multicentre, prospective registry, performed in 274
      patients. Of these, 120 (43.8%) patients were diabetic. A total of 324 lesions
      were treated with 347 SES. The primary end-point was 6-month in-stent late
      luminal loss (LL); secondary end-points included in-stent and in-segment binary
      restenosis (BR), target lesion revascularisation (TLR), target vessel
      revascularisation (TVR) and major adverse cardiac events (MACE) rate at six
      months and one-year. Pre-specified subgroup analysis included the comparison
      between diabetic and non-diabetic patients, and patients with stents of different
      diameter (2.25 mm vs. 2.5 mm) and length (</= 18 mm vs. >/= 23 mm).The mean (SD)
      reference vessel diameter of the treated segment was 2.08 (0.33) mm and lesion
      length 11.04 (6.0) mm. After six months, LL was 0.07 (0.37) mm. BR was 5.1% in
      stent and 9.1% in-segment. At one year, TLR was 5.6% and TVR was 9.0%. MACE rate
      was 2.6% at six months and 8.6% at one year with 2.3% cardiac death and 1.5% non
      fatal myocardial infarction. Stent thrombosis rate at one year was 0.8% per
      protocol. There were more MACE in diabetic patients (12.8%) than in non-diabetic
      (5.4%, p=0.046), but no other significant differences in clinical and
      angiographic parameters were noted between the subgroups analysed. CONCLUSIONS:
      The use of SES for lesions in very small coronary arteries proved to be safe and
      efficacious, irrespective of the size and length of the stents, with low
      restenosis and repeat revascularisation rates at one year.

PMID- 19758939
TI  - Two-year results of a durable polymer everolimus-eluting stent in de novo
      coronary artery stenosis (The SPIRIT FIRST Trial).
AB  - AIMS: The successful use of everolimus on a durable polymer was earlier reported
      with 6 and 12 months data from this first-in-man study. This reports the long
      term follow-up of the XIENCE V everolimus-eluting stent. METHODS AND RESULTS:
      This prospective, single-blinded, randomised, multicentre clinical trial
      evaluated the safety and efficacy of the XIENCE V everolimus-eluting coronary
      stent system versus an identical bare metal stent in the treatment of patients
      with a single de novo coronary artery stenosis of >/=50% and <100% and a vessel
      diameter of 3.0 mm as assessed by on-line quantitative coronary angiography that
      could be covered by a single 18 mm stent.Sixty patients were randomised and at
      two-year follow-up, clinical data was available in 96% and 97% of patients in the
      everolimus and control arm, respectively. Four patients were excluded due to
      protocol violations and two patients withdrew consent.In the everolimus arm no
      additional death, myocardial infarction, clinically driven TLR, or TVR events
      were observed between one and two-year follow-up. The 2-year hierarchical MACE
      rate for the everolimus arm remained 15.4% (4/26). In the control group, two
      patients had a clinically driven target lesion revascularisation. MACE rate
      increased from 21.4% (6/28) to 25.0% (7/28) in the control group. CONCLUSIONS:
      This report confirms and extends the safety and efficacy results of the durable
      polymer XIENCE V everolimus-eluting stent up to two years as compared to
      identical bare metal stents.

PMID- 19758940
TI  - Safety and efficacy of multiple, overlapping polymer-based paclitaxel-eluting
      stents.
AB  - AIMS: To provide insight on the patients with long lesions that received
      multiple, overlapping stents by reporting clinical outcomes, together with a
      detailed angiographic and intravascular ultrasound analysis of the overlap zone.
      METHODS AND RESULTS: TAXUS VI is a prospective, multicentre, double-blind, trial,
      specifically designed to assess outcomes of paclitaxel-eluting stents in longer
      lesions by randomising 446 patients (1:1) between a drug-eluting TAXUS Express2
      Moderate Release (MR) and an uncoated Express2 control stent. Multiple
      overlapping stents were implanted in 124 patients (27.8%) and are the subject of
      this report. Clinical, angiographic and IVUS outcomes at nine months were
      compared in the overlap group for patients receiving the TAXUS Express2 MR stent
      and the uncoated Express2 stent. In the overlap group, mean lesion length was
      25.1 mm with a mean stent length of 43.6 mm. At nine months, TVR was reduced by
      94% from 25.0% to 1.6% in the TAXUS patients compared with control (p=<0.0001);
      TLR was reduced by 93% from 23.3% to 1.6% (p=0.0002). Binary restenosis in the
      stented area was reduced by 89% from 45.5% in the control patients to 4.8% in the
      TAXUS patients (p<0.0001). There was a trend towards a higher 30-day myocardial
      infarction rate in the TAXUS group (7.9% vs. 1.6%; p=0.21), but by nine months,
      MACE was significantly reduced by 62.0%, from 25.0% to 9.5% in favour of the
      TAXUS patients (p=0.0305). Late acquired incomplete apposition on IVUS was
      infrequent in either group and was not located in the overlap zone, nor was the
      finding associated with late MACE. No stent thrombosis occurred in either group.
      CONCLUSIONS: The use of multiple overlapping TAXUS MR stents appears safe and
      effective in the treatment of long complex coronary artery lesions.

PMID- 19758941
TI  - Clinical results of two year dual antiplatelet therapy after primary percutaneous
      coronary intervention with paclitaxel-eluting stents: a single centre study.
AB  - AIMS: The long-term outcome of extended dual antiplatelet therapy after
      percutaneous coronary intervention (PCI) is unexplored. The purpose of the study
      was to evaluate the 2 year safety and efficacy of continuous dual antiplatelet
      treatment in patients undergoing primary PCI with paclitaxel-eluting stent (PES)
      for acute ST segment elevation myocardial infarction (STEMI). METHODS AND
      RESULTS: A series of 145 consecutive patients with STEMI underwent primary PCI
      with PES. All patients received intracoronary high dose bolus and 24 hours i.v.
      infusion of tirofiban and were then treated with dual anti-aggregation up to 2
      years. The incidence of major adverse cardiac events (MACE) was evaluated at 1
      month, 1 year, and 2 years during the follow-up period. Overall, the rate of
      cumulative MACE detected at follow-up was 2.7%, with a 1.4% incidence of
      mortality and a 0.7% need for target vessel revascularisation. No major bleeding
      occurred during follow-up (95% C.I. 0-2.6%). Safety analysis revealed that minor
      bleeding occurred in 5 patients (3.4%) at the time of PCI, and that
      thrombocytopenia developed in 3 patients (2.1%) with the extended clopidogrel
      course. During the 2 year follow-up, in-stent thrombosis was seen in only 1
      patient who stopped drug treatment against medical advice, but did not occur in
      patients who remained on dual antiplatelet therapy. CONCLUSIONS: This study shows
      in a 'real world' scenario that sustained dual antiplatelet therapy following
      primary PCI with PES in patients with STEMI is associated with very good 2 year
      clinical results.

PMID- 19758942
TI  - A randomised controlled trial of upstream administration of eptifibatide in
      patients presenting non-ST segment elevation acute coronary syndrome treated with
      an invasive strategy.
AB  - AIMS: To prospectively evaluate the benefit of upstream administration of
      eptifibatide in patients with non ST-segment elevation acute coronary syndrome
      (NSTEACS) pretreated with aspirin and clopidogrel. METHODS AND RESULTS: The
      PRACTICE study was an international, randomised, multicentre trial of 393
      patients (of 766 planned) who presented with NSTEACS. Patients were randomly
      assigned to double-blind treatment with eptifibatide (n=196) or placebo (n=197).
      Investigators used aspirin, clopidogrel with a loading dose of 300 mg followed by
      a daily dose of 75 mg, and heparin (unfractionated or low molecular weight) in
      both groups. An invasive strategy was planned within 6 to 48 hours. The primary
      endpoint was a composite of death, myocardial infarction, or urgent
      revascularisation at 30 days. The primary end point occurred in 31 patients
      (15.8%) in the eptifibatide group and in 33 patients (16.8%) in the placebo group
      (odds ratio 0.93, 95 percent confidence interval 0.53 to 1.53, P=0.70). The
      overall incidence of bleeding was not significantly different in the eptifibatide
      and the placebo groups (14.4% vs 11.3%, p=0.35). CONCLUSIONS: We did not find a
      measurable benefit of upstream administration of eptifibatide on top of aspirin
      and clopidogrel in patients presenting with NSTEACS managed by an invasive
      strategy. Further studies are warranted to further evaluate the clinical benefit
      of upstream eptifibatide in patients pretreated by clopidogrel in a larger
      population.

PMID- 19758943
TI  - Stabilisation of coronary stents using rapid right ventricular pacing.
AB  - AIMS: Excessive movement of coronary stents within the artery can make precise
      stent placement difficult. This study assessed the use of rapid right ventricular
      pacing to reduce stent motion to improve the accuracy of placement. METHODS AND
      RESULTS: During percutaneous coronary intervention, if excessive stent movement
      prevented accurate stent placement, rapid right ventricular pacing was performed
      to reduce stent motion within the coronary artery during both stent positioning
      and deployment. Post procedural angiograms were analysed by two independent
      operators to measure stent movement during sinus rhythm and during rapid right
      ventricular pacing. Rapid right ventricular pacing was considered necessary in
      ten patients. No procedural complications occurred. Mean stent excursion for all
      patients in sinus rhythm was 2.9 mm (SD 1.6) and during rapid right ventricular
      pacing this was reduced to 0.8 mm (SD 0.6) (p<0.001). Movement assessed by
      individual operators ranged from 0.7 to 6.5 mm during sinus rhythm and from 0.1
      to 2.4 mm during right ventricular pacing. CONCLUSIONS: Rapid right ventricular
      pacing is an effective and safe method to reduce stent movement and facilitate
      accurate stent deployment. This simple technique can be easily applied in any
      interventional cardiac catheterisation laboratory without the need for additional
      training or equipment.

PMID- 19758944
TI  - Rapid ventricular pacing can reduce heart motion and facilitate stent deployment
      to the optimal position during coronary artery stenting: initial experience.
AB  - AIMS: We have sometimes encountered difficulty in stent positioning, and managed
      to achieve optimal positioning of the stent by luck when there was extensive
      movement of the stent delivery system in association with the cardiac cycle. We
      assessed the safety and efficacy of rapid ventricular pacing in order to achieve
      precise positioning of the stent in this percutaneous coronary intervention (PCI)
      situation. METHODS AND RESULTS: Among 363 patients who underwent PCI, difficulty
      in positioning of the stent was encountered in 7 consecutive patients due to
      extensive movement of the stent delivery system. We applied rapid ventricular
      pacing in these 7 patients. We measured the length of motion of the stent
      delivery system relative to the coronary artery and systolic blood pressure
      before and under rapid ventricular pacing at a rate of 160 min-1. The extent of
      motion was markedly reduced by rapid ventricular pacing (7.3+/-2.6 mm to 1.7+/
      0.6 mm; p<0.001). Systolic blood pressure was decreased slightly by rapid
      ventricular pacing (116+/-15 mmHg to 90+/-7 mmHg; p=0.002), but there were no
      cases of haemodynamic degeneration or ventricular arrhythmia. CONCLUSIONS: Rapid
      ventricular pacing is a safe and promising option for precise stent positioning,
      when movement of the stent delivery system prevents precise deployment.

PMID- 19758945
TI  - Diffusion-weighted imaging to compare different cerebral protection devices in
      carotid artery stenting.
AB  - AIMS: Carotid artery stenting (CAS) is commonly performed with cerebral
      protection devices. New hyperintense lesions on diffusion-weighted MR imaging
      (DWI) were used to compare different cerebral protection devices. METHODS AND
      RESULTS: Patients (n=33) with high-grade symptomatic carotid stenosis were
      treated with CAS. Two different methods of cerebral embolic protection were used.
      In 23 patients, a filter device was placed in the distal internal carotid artery.
      In 10 patients a protection system based on the reversed-flow principle was used.
      DWI was performed before and after CAS. The number and volume of new hyperintense
      lesions in the ipsilateral hemisphere were assessed.No stroke or death was
      recorded. Twenty-three new hyperintense lesions in the ipsilateral cerebral
      hemisphere were recorded on the post-treatment DWI-series after stent placement
      in 12 of the 33 procedures (36%). In 8 of the 23 procedures (35%) performed with
      a filter device and in 4 of the 10 procedures (40%) performed with the reversed
      flow device new hyperintense lesions were revealed (13 and 10, respectively). No
      significant differences were found in the number of lesions and lesion load. The
      volume per lesion was significantly smaller in the patient group treated with
      reversed-flow device in comparison to the patient group treated with a filter
      device (median 0,048 mm3 and 0,013 mm3, respectively; p=0.03). CONCLUSION: This
      non-randomised study revealed no difference in new subclinical ischaemic lesions
      in the ipsilateral hemisphere between procedures performed with filter devices
      and procedures performed with embolic protection using the reversed-flow
      principle.

PMID- 19758946
TI  - A novel ultra-thin bare metal stent (BMS): results from a worldwide registry.
AB  - AIMS: To evaluate a new generation, thin strut, stainless steel Tsunami coronary
      stent in a contemporary percutaneous coronary intervention (PCI) practice across
      a wide geographical area. METHODS AND RESULTS: Patients (n=1,437) with single or
      multiple vessel coronary artery disease undergoing PCI in 82 sites in Europe,
      Asia, and Australia were enrolled in the MATSURI registry. Clinical follow-ups
      were scheduled at 1, 6 and 18 months. Primary endpoint was major adverse cardiac
      events (MACE) rate at 6 months. Diabetes was present in 25% of patients, 40% had
      unstable angina, 54% multivessel disease and 31% previously underwent PCI/CABG.
      Procedural success was achieved in 98.1% of patients. MACE rate was 1.8%, 7.3%,
      and 12.6% for 1, 6 and 18 month follow-up, respectively. At 6 months, the
      incidence of cardiac death, MI and TLR were 1%, 1.9% and 4.5% respectively, and
      confirmed stent thrombosis occurred in 0.2% of patients. Lower risk patients (43%
      of registry population) had six months MACE free survival of 96.7%. CONCLUSIONS:
      Based on the results of this large registry we can conclude that the Tsunami BMS
      combines excellent deliverability and safety for all, together with very low MACE
      rates for lower risk patients. Long term follow-up confirmed sustained clinical
      benefit.

PMID- 19758947
TI  - 'Fused-Gold' vs. 'Bare' stainless steel NIRflex stents of the same geometric
      design in diseased native coronary arteries. Long-term results from the NIR TOP
      Study.
AB  - OBJECTIVES: We evaluated the long-term clinical and angiographic results of
      'fused-gold' (NIRFlex Royal) and 'bare' (NIRFlex) stainless steel stents in
      patients undergoing percutaneous coronary intervention (PCI). BACKGROUND: Recent
      studies have shown high clinical and angiographic restenosis rates following the
      intracoronary implantation of 'gold-coated' stainless steel stents. The new
      'fused-gold' stent, with improved surface characteristics and flexibility, was
      developed to improve procedural and long-term results, while maintaining enhanced
      radiopacity. METHODS: A total of 305 patients (358 lesions) with symptomatic
      native coronary artery disease (CAD) undergoing native vessel PCI were randomised
      to receive a 'fused-gold' (n=147) or 'bare' (n=158) stent. Primary endpoint was
      minimal luminal diameter (MLD) at 6 months angiographic follow-up. Secondary
      endpoints included technical and procedural success, major adverse cardiac events
      (MACE), target vessel failure (TVF), angiographic binary restenosis rates, and
      additional angiographic comparisons. RESULTS: There were no major differences in
      the baseline angiographic variables or patient characteristics between the two
      groups, however there was a trend towards a higher risk in the 'fused-gold' stent
      group. Clinical and angiographic follow-up was 100% and 87% respectively. MLD at
      6 months follow-up was smaller in the 'fused-gold' stent group compared to the
      'bare' stent group (1.61+/-0.65 vs. 1.81+/-0.60 mm, respectively); Therefore, the
      null hypothesis of non-inferiority cannot be rejected (p=0.49); equivalency
      cannot be claimed for the two stent types. The 'fused-gold' stents were also
      associated with a higher angiographic binary and clinical restenosis rates (33
      vs. 18%; p=0.002 & 26.9 vs. 20.3%; p<0.001, respectively). CONCLUSION: The 'bare'
      NIRflex stent was associated with excellent long-term clinical and angiographic
      results. Taking into account the equivalence margin, the null hypothesis of non
      equivalence between the 'fused-gold' NIRflex Royal stent and the 'bare' NIRflex
      stent cannot be rejected (p=0.49), so equivalence cannot be claimed for the two
      stent types.

PMID- 19758948
TI  - Registry on a new T technique for bifurcation coronary lesions: the Utrech-"T"-
      experience.
AB  - AIMS: The goal of this study was to clinically evaluate the effectiveness of a
      new coronary stenting approach for bifurcation lesions designed to provide
      adequate main and side-branch ostial scaffolding and provide a simplified
      technique. METHODS AND RESULTS: The technique was used in 100 consecutive
      patients with suitable bifurcation lesions. Sequential placement of two stents
      was performed in all patients, resulting in complete coverage of the bifurcation
      ostium and carina with minimal crushing of a small portion of the side-branch
      stent. Clinical follow-up was done for a six months period. The rate of
      clinically driven target vessel revascularisation at six months was 4%. One
      patient died during follow-up. Subacute thrombosis occurred in two patients.
      CONCLUSIONS: Treatment of bifurcation lesions using this new approach is
      feasible, with a low rate of procedural and clinical events. Larger trials with
      angiographic follow-up are necessary to prove the potential advantage of this
      approach relatively to the currently used techniques for the treatment of
      coronary bifurcations.

PMID- 19758949
TI  - Proximal protection in carotid artery stenting: rationale and recent findings.

PMID- 19758950
TI  - Uncoupling protein 2-mediated thermogenesis in vulnerable atherosclerotic
      plaques.
AB  - Timely detection of vulnerable atherosclerotic plaques is of the utmost
      importance to prevent acute clinical events, such as unstable angina, myocardial
      infarction and sudden death. Advanced plaques show a dense infiltration of
      macrophages, of which a subpopulation strongly expresses uncoupling protein 2
      (UCP2). This protein uncouples adenosine triphosphate (ATP) production from
      mitochondrial respiration and thereby converts the loss of potential energy in
      heat production. In early atherosclerotic lesions, UCP2 seems to fulfil an
      atheroprotective effect by reducing reactive oxygen species (ROS) production
      and/or by inhibiting monocyte recruitment. Because the amount of macrophages in
      these lesions is limited, effects on plaque temperature cannot be detected. As
      the macrophage content of the plaque increases and the plaque progresses toward
      an unstable phenotype, ROS production is overwhelming, and possibly cannot be
      counteracted by the antioxidant properties of UCP2. However, the increasing
      number of UCP2-positive macrophages inside advanced plaques correlates with
      increased plaque temperature. This thermogenic effect can be detected by
      intravascular thermography and may be indicative of rupture-prone regions. Thus,
      UCP2 expression in macrophages in advanced plaques can be considered a
      biochemical link between plaque temperature and vulnerability.

PMID- 19758951
TI  - Coronary sinus stent implantation improves acute ischaemic mitral valve
      regurgitation; an experimental safety and efficacy study.
AB  - AIMS: Percutaneous implantation of a large stent was performed in the coronary
      sinus of pigs, to assess safety and immediate efficacy for reduction of acute
      ischaemic mitral regurgitation. METHODS AND RESULTS: Acute ischaemic mitral
      regurgitation (MR) was produced in seven pigs, continuously monitored with
      echocardiography, during repeated balloon inflations in the proximal left
      circumflex artery. The protocol was repeated following placement of a stent in
      the coronary sinus. Five pigs survived the period of acute ischaemia and
      developed severe mitral regurgitation (>/=3+/4+). Following successful stent
      implantation, the MR area decreased from 2.4+/-0.4 cm2 to 1.1+/-0.6 cm2 (p=0.016)
      and the proximal isovelocity surface area (PISA) MR flow from 63.9+/-37.3 ml/sec
      to 44.0+/-35.0 ml/sec (p=0.029). Coronary sinus stent prevented the ischaemia
      induced increase in septal-lateral mitral annulus dimension (p=0.041) and left
      ventricular dilatation. Three animals were allowed to recover and underwent
      histological analysis of the coronary sinus stent at 30 days, showing
      endothelialisation and minimal hyperplasia, without thrombus formation.
      CONCLUSIONS: A percutaneously deployed stent in the coronary sinus may help to
      decrease the severity of acute ischaemic mitral regurgitation.

PMID- 19758952
TI  - GENIE catheter for liquid local drug delivery.

PMID- 19758953
TI  - Kartagener's Syndrome.

PMID- 19758954
TI  - Ultrasonic and pathological evidence of a neo-intimal plaque rupture in patients
      with bare metal stents.

PMID- 19758955
TI  - Congenital multiple clustered dermatofibroma: dermatoscopic findings.

PMID- 19758956
TI  - Is it really possible to differentiate insect bite-like reaction and nodular
      variant of eosinophilic cellulitis in a healthy person?

PMID- 19758957
TI  - Analysis of myeloperoxidase promotor polymorphism and enzyme activity in Turkish
      patients with vitiligo.
AB  - Vitiligo is an acquired depigmentary disorder characterized by white areas of the
      skin due to loss of epidermal melanocytes. Oxidative stress and free radicals are
      suggested as important phenomena in the pathogenesis of vitiligo. Myeloperoxidase
      is a lysosomal enzyme of polymorphonuclear leukocytes and acts as a catalyst in
      the production of hypochlorous acid, a powerful oxidant. In this study we
      analysed enzyme activity and gene polymorphism of myeloperoxidase in patients
      with vitiligo. Fifty-four patients with vitiligo and 58 healthy controls were
      enrolled to this study. Patient groups were subdivided according to localization
      of the lesions; generalized, acrofacial and local. Plasma myeloperoxidase enzyme
      activity was determined with ELISA and G-463A gene (-463) polymorphism with the
      PCR-RFLP (AciI) method. The plasma MPO level was significantly lower in vitiligo
      patients than in the healthy controls (p = 0.005), however, it was not
      significantly different among subtypes of vitiligo (p = 0.8). A significant
      difference was not observed for G-463A genotype and allele distribution in
      patients with vitiligo. In conclusion, the present study is the first study
      investigating MPO G-463A polymorphism and enzyme levels, which warrants further
      studies with higher patient numbers and broader polymorphism panels.

PMID- 19758958
TI  - Cellular neurothekeoma of the vulva, an unusual location.

PMID- 19758959
TI  - [PET/CT in breast cancer: an update].
AB  - The authors discuss the various roles of 18F-FDG PET/CT in the management of
      breast cancer. Roles of new tracers such as F-18 fluoro-L-thymidine (a marker of
      cell proliferation), 18-fluoro-17-B-estradiol (marker of estrogen receptor) and
      sodium fluoride (marker of bone matrix) are also mentioned. There is little
      justification for the use of FDG-PET/CT in patient with clinically T1 (< or = 2
      cm) N0 tumours. Notably, it cannot be used as a substitute to SLNB "sentinel
      lymph node biopsy" for axillary staging due to limited sensitivity for the
      detection of small metastases. The case is different in higher risk patients, and
      especially so in patients with locally advanced disease. FDG-PET/CT in these
      patients might depict lymph node involvement in the level III of Berg or in
      supraclavicular or internal mammary basins. It might also uncover occult distant
      metastases, notably, early osteomedullary infiltration. Thus, for these tumors,
      initial PET/CT can enable better intramodality treatment planning or a change in
      treatment. PET/CT as a whole-body examination is also very efficient in case of
      suspicion of recurrence. On the other hand, many studies show that this
      functional imaging could be used to assess early response to neoadjuvant
      chemotherapy or to chemotherapy of metastatic disease. 18FDG-PET/CT could thus
      become an unavoidable modality to answer various clinical situations.

PMID- 19758960
TI  - [Treatment of pituitary adenomas].
AB  - According to epidemiological studies, the prevalence of pituitary adenomas is
      16.5% and the majority of them are "incidentalomas". The symptoms of pituitary
      disorders are often non-specific; disturbances of pituitary function, compression
      symptoms, hypophysis apoplexy or accidental findings may help the diagnosis. The
      hormonal evaluation of pituitary adenomas is different from the algorithm used in
      the disorders of peripheral endocrine organs. The first-line therapy of
      prolactinomas are the dopamine agonists, and the aims of the treatment are to
      normalize the prolactin level, restore fertility in child-bearing age, decrease
      tumor mass, save or improve the residual pituitary function and inhibit the
      relapse of the disease. The available dopamine agonists in Hungary are
      bromocriptine and quinagolide. In case of tumors with good therapeutic response,
      medical therapy can be withdrawn after 3-5 years; hyperprolactinemia will not
      recur in 2/3 of these patients. Neurosurgery is the primary therapy of GH-, ACTH
      , TSH-producing and inactive adenomas. In the last decades, significant
      improvement has been reached in surgical procedures, resulting in low mortality
      rates. Acromegalic patients with unresectable tumors have a great benefit from
      somatostatin analog treatment. The growth hormone receptor antagonist pegvisomant
      is the newest modality for the treatment of acromegaly. The medical therapy of
      Cushing's disease is still based on the inhibition of steroid production. A new,
      promising somatostatin analog, pasireotide is evaluated in clinical trials. The
      rare TSH-producing tumor can respond to both dopamine agonist and somatostatin
      analog therapy. The application of conventional radiotherapy has decreased;
      radiotherapy is mainly used in the treatment of invasive, incurable or malignant
      tumors. Further studies are needed to elucidate the exact role of radiosurgery
      and fractionated stereotaxic irradiation in the treatment of pituitary tumors.

PMID- 19758961
TI  - [Hypertension in diabetes mellitus].
AB  - Hypertension can be detected very often in patients with diabetes mellitus. In
      some cases, hypertension develops as a consequence of diabetic nephropathy.
      Although diabetic nephropathy may occur both in type 1 and in type 2 diabetes,
      some differences can be observed in the clinical picture according to the type of
      diabetes. In the majority of patients with type 2 diabetes or prediabetes, the
      pathomechanism of hypertension can be explained by the concept of the metabolic
      syndrome. In order to avoid or decrease target organ damage, the goal of
      antihypertensive treatment in diabetes mellitus is to be set at <130/80 mmHg. The
      initial antihypertensive therapy is usually based on the evaluation of the global
      cardiovascular risk. Apart from modifying nutrition and lifestyle,
      pharmacological treatment with combination of antihypertensive drugs is generally
      required in order to achieve treatment goal. Diabetic or antidiabetic properties
      of antihypertensive drugs and antihypertensive characteristics of some
      antidiabetic drugs should be considered in the everyday clinical practice.

PMID- 19758962
TI  - [Ocular signs of increased intracranial pressure].
AB  - Ocular signs developing as a result of increased intracranial pressure help the
      early diagnosis and prevention of severe and progressive pathological processes.
      Functional signs of the forming papillary oedema and central eye movement
      disorders may be predictors of increasing intracranial pressure. The functional
      tests of the antechiasmal optic nerve (i.e. the measurement of the visual field,
      fluorescein angiography of the retinal vessels, optic coherent tomography,
      ultrasound examinations of the carotid or vertebral arteries, and state-of-the
      art neuroradiological methods) may provide help in determining the
      progression/remission of the increasing intracranial pressure and the efficacy of
      the treatment, and in differential diagnosis, as well. Adequate systemic therapy
      in time allows preventing irreversible incomplete or complete blindness,
      accompanied by the atrophy of the optic nerve, which is caused by increased
      intracranial pressure.

PMID- 19758963
TI  - [New method for evaluation of left ventricular dyssynchrony and of the success of
      cardiac resynchronization therapy: real-time 3-dimensional echocardiography].
AB  - Based on recently available clinical experiences and criteria, one third of heart
      failure patients prove to be non-responder despite cardiac resynchronization
      therapy (CRT) and lack improvement in their clinical status despite optimal
      treatment. This fact leaded to a new research direction to find a parameter
      measured by a non-invasive imaging method (for instance echocardiography), which
      is able to evaluate left ventricular dyssynchrony and to select patients capable
      for CRT. The aim of this review is to demonstrate the possible role of the newest
      echocardiography method, the real-time three-dimensional echocardiography based
      on the available literature.

PMID- 19758965
TI  - Compound heterozygosity for hemoglobin S [beta6(A3)Glu6Val] and hemoglobin Korle
      Bu [beta73(E17)Asp73Asn].
AB  - We report a case of compound heterozygous hemoglobins S [beta6(A3)Glu6Val] and
      Korle-Bu [beta73(E17)Asp73Asn] in a 2-year-old girl. This hemoglobin genotype is
      associated with a benign clinical course, much like the sickle cell trait;
      however, its laboratory characteristics are very similar to compound heterozygous
      hemoglobin S and hemoglobin D-Los Angeles [beta121(GH4)Glu121Gln], which produces
      severe sickling hemolytic anemia. We describe laboratory data used to resolve
      this important differential diagnosis and review the interactions between
      hemoglobin S and the variant hemoglobins that may account for the different
      clinical phenotypes in compound heterozygotes.

PMID- 19758966
TI  - Ethnic and genetic causes of neutropenia: clinical and therapeutic implications.
AB  - The white blood cell count represents clinical data linked with different
      pathologic conditions, as well as with lifestyle. Another very important
      condition that affects the number of leukocytes is race and ethnic group-the
      geographic zone of origin. Genetic studies have identified the gene that controls
      the expression of the Duffy antigen receptor for chemokine (DARC), which is
      associated with the ethnic group to which individuals belong. The single
      nucleotide polymorphism strongly associated with race is DARC rs2814778.
      Currently, it is the only condition that can explain the difference in white
      blood cell count between different ethnic groups. In a society increasingly
      characterized by multiracial issues, the leukopenia and/or neutropenia in ethnic
      groups must be known and accurately assessed clinically. Improved knowledge of
      this association may help in optimizing therapeutic approaches, mainly for
      African patients with severe diseases, cancer in particular. Recently,
      preclinical data have also suggested a link between the Duffy antigen and
      coagulation. This review also discusses the main causes of genetic neutropenia.

PMID- 19758967
TI  - The coinheritance of beta- and alpha- thalassemia: a review of one patient and
      her family.
AB  - The diagnosis and management of alpha-thalassemia may be complicated by the
      variability of the phenotype, which is due to the interaction of coinherited
      alpha-thalassemia and the variable severity of beta-thalassemia mutations. A well
      documented case of complex beta- and alpha-thalassemia coinheritance is
      described. Laboratory and clinical data for the patient and her family are
      reviewed. The patient is an asymptomatic girl, one of identical twins. She
      presented at 1 month of age for follow-up of an abnormal newborn-screening result
      (hemoglobin F only), which initially suggested homozygosity for beta-thalassemia.
      Extensive studies on the patient and family revealed that she had coinherited
      alpha-thalassemia traits and homozygous beta-thalassemia. This case demonstrates
      the interaction of coinherited alpha- and beta-thalassemia with the resultant
      amelioration of the clinical phenotype. It also highlights the importance of
      family studies and close follow-up in diagnosing complex hemoglobinopathies.

PMID- 19758969
TI  - High plasma endostatin level unaffected by low-molecular weight heparin in
      hemodialysis patients--a preliminary report.
AB  - PURPOSE: Endostatin (ES) is a potent inhibitor of angiogenesis and
      neoangiogenesis, and interestingly its activity is modified by heparin. To
      understand if low-molecular weight heparins have different clinical profiles
      regarding this cytokine, we studied the effects of enoxaparin, nadroparin and
      dalteparin administered for hemodialysis (HD) anticoagulation on plasma ES
      levels. MATERIAL AND METHODS: Seventeen chronic HD patients completed this
      prospective, crossover trial. They were randomized into 6 groups - each patient
      was administered enoxaparin (effective dose of 0.75 mg/kg), nadroparin (70.4
      IU/kg) and dalteparin (78.6 IU/kg) in 3 time periods of 2 months each. At the end
      of each period plasma levels of ES were measured at the start and at 10 min and
      180 min of the HD procedure. RESULTS: Mean predialysis plasma ES levels in HD
      patients were extremely high for all three heparins used. We observed no changes
      in ES levels during dialysis, there were also no differences in ES profiles for
      each of the low-molecular weight heparins used. CONCLUSIONS: Plasma ES levels are
      unusually high in chronic HD patients and the significance of this fact needs
      future research. ES levels do not change after heparin administration and at
      least in that aspect enoxaparin, nadroparin and dalteparin are equal.

PMID- 19758970
TI  - Pelvic confined idiopathic retroperitoneal fibrosis  mimicking a large tumor.
AB  - Idiopathic retroperitoneal fibrosis (IRF) entirely confined to the pelvic cavity
      is an extremely rare clinical entity. Herein, is described the case of a 36- year
      old male who presented with clinical and imaging manifestations of a large pelvic
      tumor. Exploratory laparotomy revealed a large mass in the right pelvis
      originating from the retroperitoneal space, displacing the right iliac vessels,
      the right ureter and the urinary bladder completely to the left. A laborious
      resection of the mass measuring 14 x 10cm was performed. Histopathological
      examination and detailed immunohistochemistry analysis were suggestive of
      idiopathic retroperitoneal fibrosis with no evidence of malignancy. This is a
      very rare case regarding localization and clinical presentation of idiopathic
      retroperitoneal fibrosis. We conclude that IRF should be included in the
      differential diagnosis of patients presenting with a pelvic mass even if there is
      no involvement of the typical para aortic area.

PMID- 19758971
TI  - Assessment of aprotinin influence on periodontal  clinical status and matrix
      metalloproteinases 1, 2  and their tissue inhibitors saliva concentrations  in
      patients with chronic periodontitis.
AB  - PURPOSE: Assessment of the effect of treatment with aprotinin-containing drug on
      the clinical status of the periodontal tissue and on the concentrations of
      metalloproteinases released in the course of periodontitis (MMP-1, MMP-2) as well
      as their tissue inhibitors (TIMP-1 and TIMP-2) in the saliva of patients with
      chronic periodontitis (CP). MATERIAL/METHODS: The study involved 25 subjects with
      CP (39-68 years), including 16 women and 9 men. The patients were prescribed
      aprotinin preparation to be taken for 2 weeks. The control group (C) involved 14
      healthy subjects (41-65 years), including 10 women and 4 men. Two periodontal
      indices were assessed: the approximal plaque index (API) and bleeding on probing
      index (BOP). Periodontal pocket depth and clinical attachment level were also
      evaluated. The concentrations of MMP-1 and MMP-2 as well as TIMP-1 and TIMP-2
      were determined by the ELISA method. RESULTS: The mean salivary MMP-1
      concentration in patients with CP was significantly higher before and after
      treatment, as compared to healthy subjects. The mean salivary MMP-2 concentration
      in CP patients at baseline was also higher as compared to the C group and
      increased after treatment. The mean salivary TIMP-1 and TIMP-2 concentration in
      CP patients was higher as compared to C group and increased after treatment.
      CONCLUSIONS: Since the mean MMPs levels were found to be growing it can be
      assumed that aprotinin has no significant effect on the regulation of MMPs in the
      saliva of CP patients. It thus seems that aprotinin application after scaling has
      no additional therapeutic effect.

PMID- 19758972
TI  - Targeting Notch signaling in pancreatic cancer patients--rationale for new
      therapy.
AB  - Pancreatic cancer is one of the most aggressive and devastating human
      malignancies. Despite new knowledge in the molecular profile of pancreatic cancer
      and its precursor lesions, survival rates have changed very little over the last
      40 years. Therefore, a better understanding of the detailed mechanisms underlying
      the pathogenesis of this disease is critical if we expect to develop new and
      effective strategies for prevention, early diagnosis and treatment of pancreatic
      cancer. The review herein focuses on a distinctive signaling pathway, the Notch
      pathway, which has recently been associated with carcinogenesis, including
      pancreatic cancer. It is aimed at summarizing key results which support a role
      for this pathway in the initiation, progression and maintenance of pancreatic
      cancer as a rationale for targeting and inhibiting this pathway in pancreatic
      cancer patients.

PMID- 19758973
TI  - Reciprocal chromosome translocations involving short arm  of chromosome 9 as a
      risk factor of unfavorable pregnancy  outcomes after meiotic malsegregation 2:2.
AB  - PURPOSE: Genetic counseling of carriers with individual chromosome translocation
      requires information on how balanced reciprocal chromosome translocations (RCT)
      will segregate, what possible form of unbalanced embryo/fetus/child can occur,
      and the survival rates that have been observed in the particular families. We
      collected new empirical data and evaluated pedigrees of RCT carriers involving 9p
      in order to improve risk figures. MATERIAL AND METHODS: Empirical data on 241
      pregnancies of 70 carriers were collected from 32 pedigrees of carriers of RCT at
      risk for a single 9p segment imbalance (RCT9p) from the literature and
      unpublished data. The probability rates of particular types of pathology have
      been calculated according to the method of Stengel-Rutkowski and Stene.
      Cytogenetic interpretation was based on GTG, RBG and FISH techniques. RESULTS:
      The probability rate for unbalanced offspring at birth for the whole group of
      pedigrees was calculated as 17.8+/-3% (33/185) (high risk). Considering the size
      of the imbalanced segment of 9p, the probability rates for RCT carriers with a
      breakpoint position at 9p22 at 9p13 and at 9p11.2 were estimated separately, and
      were found as 21.2+/-4.4% (18/85), 25+/-8.8% (6/24) and 11.8+/-3.7% (9/76),
      respectively. For unbalanced fetuses at 2nd prenatal diagnosis, we found the risk
      value as 57.9+/-11.3 % (11/19). The risk value for unkaryotyped stillbirths/early
      deaths of newborns and miscarriages were 5.4+/-1.7% (10/185) (medium risk) and
      13+/-2.8% (rate 24/185) (high risk) respectively. CONCLUSIONS: Our results showed
      that the recurrence probability rates are different for particular categories of
      unfavorable pregnancy outcomes. How much they are dependent on the size of 9p
      chromosome segments taking part in the imbalance needs further studies based on a
      larger number of observations.

PMID- 19758974
TI  - Serum concentration of interleukin 10, anti-mannan  Candida antibodies and the
      fungal colonization  of the gastrointestinal tract in patients with ulcerative
      colitis.
AB  - PURPOSE: There is evidence for the immunomodulation disorders in the response to
      intestinal flora in inflammatory bowel disease, however, the role of yeasts in
      the aetiopathogenesis of ulcerative colitis has not been fully clarified. The aim
      of this study was to assess the serum concentration of interleukin 10 (IL-10),
      serum levels of anti-mannan Candida antibodies and fungal colonization of the
      lower part of the gastrointestinal tract in accordance with the clinical course
      of ulcerative colitis. MATERIAL/METHODS: In 42 consecutive patients with
      ulcerative colitis serum concentration of IL-10 and anti-mannan Candida
      antibodies serum levels were measured with ELISA and the quantitative and
      qualitative fungal cultures of stool samples were performed. RESULTS: In 20
      patients IL-10 serum concentration was below the test sensitivity and in 11
      patients it ranged between 0.78 and 9.43 (mean 3.38 +/- 2.8) pg/mL. Anti-mannan
      Candida antibodies were detected in 8 subjects (19.04%). Stool cultures revealed
      significant fungal colonization in 3 (8.33%) patients with the predominance of
      Candida albicans. In comparison with mild/moderate UC, IL-10 serum concentration
      was not higher in patients with severe course of the disease. CONCLUSIONS: The
      results of our study show that IL-10 serum concentration correlates neither with
      the disease activity nor with the levels of anti-mannan Candida antibodies and
      the fungal colonization of the gastrointestinal tract in ulcerative colitis. It
      seems that IL-10 serum concentration cannot be a universal marker for the
      assessment of ulcerative colitis activity. Moreover, anti-mannan Candida
      antibodies and significant fungal colonization are present in the minority of
      patients with ulcerative colitis suggesting that yeasts have minor, if any,
      influence on the clinical course of the disease.

PMID- 19758975
TI  - Intimate partner violence attitudes and experience among women and men in Uganda.
AB  - This study examines intimate partner violence (IPV) attitudes and experience
      among women and men in Uganda to inform IPV-prevention programs in the region.
      Nationally representative population-based data from women aged 15 to 49 and men
      aged 15 to 54 were collected between May and October 2006 as part of the Uganda
      Demographic and Health Survey. The survey included questions on women's and men's
      attitudes toward wife beating and information on IPV victimization (women) and
      perpetration (men). More than half of men and nearly three quarters of women have
      attitudes supportive of wife beating in Uganda. More than half of married women
      report IPV victimization, and 40% of married men report perpetration. Women and
      men who reported witnessing their fathers beating their mothers were more likely
      to report IPV victimization (perpetration for men). Witnessing violence was also
      associated with positive attitudes toward wife beating among men. IPV-prevention
      programs need to address the important role of having witnessed wife beating
      between the mother and the father on men's subsequent attitudes and behaviors.
      Women who witnessed wife beating are also the most likely to have supportive
      attitudes and IPV experience, possibly indicating that their relationship
      expectations are different than women who did not witness violence. Community
      based prevention programs targeting men and women are needed in Uganda and
      elsewhere in sub-Saharan Africa where gender norms that justify IPV prevail.

PMID- 19758976
TI  - Can good law make up for bad politics? The case of Eluana Englaro.

PMID- 19758977
TI  - The representativeness of sentinel practice networks.
AB  - BACKGROUND: The representativeness of practice networks is important when using
      the information obtained to guide health policy. AIM: To develop a model for
      examining the representativeness of practice networks. METHODS: Comparison of
      surveyed population, practice structure and prescribing characteristics with the
      national data using the Weekly Returns Service (WRS) for 2006 as an example of
      practice network. The population monitored was compared with the national PCT
      population. The practice postcode was linked to the Index of Multiple Deprivation
      and the distribution compared with the national equivalents. Doctor and practice
      specific structural data (obtained by questionnaire) and practice-prescribing
      data were compared with the national equivalents. The significance of differences
      was evaluated using non-parametric tests. RESULTS: The WRS population was closely
      matched with the national data by age, gender and deprivation index. Compared
      with the national equivalents, WRS practices, included more younger GPs, had a
      larger average list per GP and fewer practices with a list of less than 1499 per
      GP. Prescribing patterns were similar to their PCT equivalents excepting for
      small reductions of antibacterial prescribing (items 7% and cost 5%). CONCLUSION:
      We demonstrate a low-cost model methodology for examining the representativeness
      of practice networks using independent data with minimum practice input.

PMID- 19758978
TI  - Challenges in investigating transient rash illness in nursery children.
AB  - INTRODUCTION: In October 2007, the Thames Valley Health Protection Unit (TVHPU)
      was notified by a parent that her child developed a transient rash after eating
      lunch at a nursery in Oxfordshire. An initial investigation undertaken by TVHPU
      was escalated when similar incidents were reported in nurseries in other parts of
      England. METHODS: A detailed epidemiological and food tracing investigation was
      conducted to ascertain the aetiology. RESULTS: Investigations revealed 11
      incidents affecting 164 children between July and November 2007 in six nurseries
      operated by two companies. The symptoms included a transient rash around the
      mouth and hands of children who ate meals prepared on site by the nurseries.
      Consumption of the lunch main course appeared to be a strong aetiological factor.
      Expert opinion pointed to biogenic amines (e.g. histamine) as a possible cause
      for the symptoms displayed, but there was insufficient evidence to support
      testing of food samples. CONCLUSION: The incident highlighted significant gaps in
      reporting of unexplained symptoms among children in nurseries, indicating that
      such incidents do not always come to the attention of public health authorities.
      Timely notification to HPUs will enable prompt investigation, increase the
      likelihood of identifying the cause and inform appropriate responses to prevent
      future incidents.

PMID- 19758980
TI  - Microvolt T-wave alternans during exercise and pacing are not comparable.
AB  - AIMS: The absence of microvolt T-wave alternans (MTWA) identifies a group of
      patients who are at low risk for ventricular arrhythmia or sudden cardiac death.
      However, in exercised assessed MTWA, 20-40% of all test results are
      indeterminate. We hypothesised that MTWA during pacing would yield less
      indeterminate results. METHODS AND RESULTS: Thirty patients with ischaemic
      cardiomyopathy and prior dual chamber implantable cardioverter defibrillator
      implantation were enrolled. All patients underwent sequential MTWA testing using
      an exercise (E), atrial-paced (A), and atrioventricular-paced (AV) protocol. The
      number of indeterminate tests was lower during pacing (A: 17%; AV: 3%) compared
      with exercise (37%) (E vs. A: P = 0.015, E vs. AV: P = <0.001). When positive and
      indeterminate test results were grouped as non-negative, the concordance rates
      between E and A, E and AV, and A and AV were 60% (kappa = 0.17), 57% (kappa =
      0.058), and 70% (kappa = 0.348), respectively. If indeterminate results were
      excluded, agreements were 60% (kappa = 0.19), 50% (kappa = 0.129) and 67% (kappa
      = 0.33), respectively. CONCLUSION: Indeterminate test results are less common
      during pacing. However, there is a low concordance rate between test results
      using different protocols. This necessitates further study to determine the
      predictive value of each method in high risk patients with ischaemic
      cardiomyopathy.

PMID- 19758979
TI  - Phenotyping male infertility in the mouse: how to get the most out of a 'non
      performer'.
AB  - BACKGROUND: Functional male gametes are produced through complex processes that
      take place within the testis, epididymis and female reproductive tract. A
      breakdown at any of these phases can result in male infertility. The production
      of mutant mouse models often yields an unexpected male infertility phenotype. It
      is with this in mind that the current review has been written. The review aims to
      act as a guide to the 'non-reproductive biologist' to facilitate a systematic
      analysis of sterile or subfertile mice and to assist in extracting the maximum
      amount of information from each model. METHODS: This is a review of the original
      literature on defects in the processes that take a mouse spermatogonial stem cell
      through to a fully functional spermatozoon, which result in male infertility.
      Based on literature searches and personal experience, we have outlined a step-by
      step strategy for the analysis of an infertile male mouse line. RESULTS: A wide
      range of methods can be used to define the phenotype of an infertile male mouse.
      These methods range from histological methods such as electron microscopy and
      immunohistochemistry, to hormone analyses and methods to assess sperm maturation
      status and functional competence. CONCLUSION: With the increased rate of
      genetically modified mouse production, the generation of mouse models with
      unexpected male infertility is increasing. This manuscript will help to ensure
      that the maximum amount of information is obtained from each mouse model and, by
      extension, will facilitate the knowledge of both normal fertility processes and
      the causes of human infertility.

PMID- 19758981
TI  - Riboflavin-responsive lipid-storage myopathy caused by ETFDH gene mutations.
AB  - BACKGROUND: Lipid-storage myopathy (LSM), defined by triglyceride accumulation in
      muscle fibres, is a heterogeneous group of lipid metabolic disorders
      predominantly affecting skeletal muscle. In the past 15 years, more than 200
      cases of LSM have been reported in the Chinese literature, but the accurate
      pathogenic mechanisms are still unknown. OBJECTIVE: In order to gain more insight
      into the metabolic and genetic dysfunctions of LSM, the authors described a group
      of Chinese patients with LSM who were very responsive to isolated riboflavin
      treatment (riboflavin responsive LSM, RR-LSM). METHODS: Nineteen consecutive LSM
      patients collected during 1995-2007 in our Neuromuscular Laboratory who were
      dramatically responsive to riboflavin and presented with proximal muscle
      weakness, exercise intolerance and elevated serum CK but without episodic
      encephalopathy were subjected to pathological, biochemical and molecular
      analysis. RESULTS: On the basis of muscle pathology, all 19 patients were
      diagnosed as LSM. Seventeen patients were suspected of having multiple acyl
      coenzyme A dehydrogenase deficiency (MADD) according to blood acylcarnitine
      profiles and urine organic acid analysis. Genetic analysis identified 19 novel
      mutations in ETFDH gene in 18 patients, among which one was homozygote, 16 were
      compound heterozygotes, and one was a single heterozygote. No pathogenic mutation
      was detected in ETFA or ETFB genes. Western blot analysis showed there was no
      significant decrease in ETF:QO expression except for one patient. CONCLUSIONS:
      The research findings suggest that the majority of Chinese patients with RR-LSM
      are caused by a mild type of MADD with unique myopathy which is due to ETFDH gene
      mutation.

PMID- 19758982
TI  - Freezing of gait in Parkinson's disease: a perceptual cause for a motor
      impairment?
AB  - While freezing of gait (FOG) is typically considered a motor impairment, the fact
      that it occurs more frequently in confined spaces suggests that perception of
      space might contribute to FOG. The present study evaluated how doorway size
      influenced characteristics of gait that might be indicative of freezing. Changes
      in spatiotemporal aspects of gait were evaluated while walking through three
      different-sized doorways (narrow (0.675 m wide x 2.1 m high), normal (0.9 m wide
      x 2.1 m high) and wide (1.8 m wide x 2.1 m high)) in three separate groups: 15
      individuals with Parkinson's disease confirmed to be experiencing FOG at the time
      of test; 16 non-FOG individuals with Parkinson's disease and 16 healthy age
      matched control participants. Results for step length indicated that the FOG
      group was most affected by the narrow doorway and was the only group whose step
      length was dependent on upcoming doorway size as indicated by a significant
      interaction of group by condition (F(4,88)=2.73, p<0.034). Importantly, the FOG
      group also displayed increased within-trial variability of step length and step
      time, which was exaggerated as doorway size decreased (F(4,88)=2.99, p<0.023). A
      significant interaction between group and condition for base of support measures
      indicated that the non-FOG participants were also affected by doorway size
      (similar to Parkinson's disease FOG) but only in the narrow doorway condition.
      These results support the notion that some occurrences of freezing may be the
      result of an underlying perceptual mechanism that interferes with online movement
      planning.

PMID- 19758983
TI  - Molecular basis of transcriptional mutagenesis at 8-oxoguanine.
AB  - Structure-function analysis has revealed the mechanism of yeast RNA polymerase II
      transcription at 8-oxoguanine (8-oxoG), the major DNA lesion resulting from
      oxidative stress. When polymerase II encounters 8-oxoG in the DNA template
      strand, it can misincorporate adenine, which forms a Hoogsteen bp with 8-oxoG at
      the active center. This requires rotation of the 8-oxoG base from the standard
      anti- to an uncommon syn-conformation, which likely occurs during 8-oxoG loading
      into the active site. The misincorporated adenine escapes intrinsic proofreading,
      resulting in transcriptional mutagenesis that is observed directly by mass
      spectrometric RNA analysis.

PMID- 19758984
TI  - Hydrophobic core mutations associated with cataract development in mice
      destabilize human gammaD-crystallin.
AB  - The human eye lens is composed of fiber cells packed with crystallins up to 450
      mg/ml. Human gammaD-crystallin (HgammaD-Crys) is a monomeric, two-domain protein
      of the lens central nucleus. Both domains of this long lived protein have double
      Greek key beta-sheet folds with well packed hydrophobic cores. Three mutations
      resulting in amino acid substitutions in the gamma-crystallin buried cores (two
      in the N-terminal domain (N-td) and one in the C-terminal domain (C-td)) cause
      early onset cataract in mice, presumably an aggregated state of the mutant
      crystallins. It has not been possible to identify the aggregating precursor
      within lens tissues. To compare in vivo cataract-forming phenotypes with in vitro
      unfolding and aggregation of gamma-crystallins, mouse mutant substitutions were
      introduced into HgammaD-Crys. The mutant proteins L5S, V75D, and I90F were
      expressed and purified from Escherichia coli. WT HgammaD-Crys unfolds in vitro
      through a three-state pathway, exhibiting an intermediate with the N-td unfolded
      and the C-td native-like. L5S and V75D in the N-td also displayed three-state
      unfolding transitions, with the first transition, unfolding of the N-td, shifted
      to significantly lower denaturant concentrations. I90F destabilized the C-td,
      shifting the overall unfolding transition to lower denaturant concentrations.
      During thermal denaturation, the mutant proteins exhibited lowered thermal
      stability compared with WT. Kinetic unfolding experiments showed that the N-tds
      of L5S and V75D unfolded faster than WT. I90F was globally destabilized and
      unfolded more rapidly. These results support models of cataract formation in
      which generation of partially unfolded species are precursors to the aggregated
      cataractous states responsible for light scattering.

PMID- 19758985
TI  - Two pathways for cyclooxygenase-2 protein degradation in vivo.
AB  - COX-2, formally known as prostaglandin endoperoxide H synthase-2 (PGHS-2),
      catalyzes the committed step in prostaglandin biosynthesis. COX-2 is induced
      during inflammation and is overexpressed in colon cancer. In vitro, an 18-amino
      acid segment, residues 595-612, immediately upstream of the C-terminal
      endoplasmic reticulum targeting sequence is required for N-glycosylation of
      Asn(594), which permits COX-2 protein to enter the endoplasmic reticulum
      associated protein degradation system. To determine the importance of this COX-2
      degradation pathway in vivo, we engineered a del595-612 PGHS-2 (Delta 18 COX-2)
      knock-in mouse lacking this 18-amino acid segment. Delta 18 COX-2 knock-in mice
      do not exhibit the renal or reproductive abnormalities of COX-2 null mice. Delta
      18 COX-2 mice do have elevated urinary prostaglandin E(2) metabolite levels and
      display a more pronounced and prolonged bacterial endotoxin-induced febrile
      response than wild type (WT) mice. Normal brain tissue, cultured resident
      peritoneal macrophages, and cultured skin fibroblasts from Delta 18 COX-2 mice
      overexpress Delta 18 COX-2 relative to WT COX-2 expression in control mice. These
      results indicate that COX-2 can be degraded via the endoplasmic reticulum
      associated protein degradation pathway in vivo. Treatment of cultured cells from
      WT or Delta 18 COX-2 mice with flurbiprofen, which blocks substrate-dependent
      degradation, attenuates COX-2 degradation, and treatment of normal mice with
      ibuprofen increases the levels of COX-2 in brain tissue. Thus, substrate turnover
      dependent COX-2 degradation appears to contribute to COX-2 degradation in vivo.
      Curiously, WT and Delta 18 COX-2 protein levels are similar in kidneys and
      spleens from WT and Delta 18 COX-2 mice. There must be compensatory mechanisms to
      maintain constant COX-2 levels in these tissues.

PMID- 19758986
TI  - Limiting role of protein disulfide isomerase in the expression of collagen-tailed
      acetylcholinesterase forms in muscle.
AB  - The expression of acetylcholinesterase (AChE) in skeletal muscle is regulated by
      muscle activity; however, the underlying molecular mechanisms are incompletely
      understood. We show here that the expression of the synaptic collagen-tailed AChE
      form (ColQ-AChE) in quail muscle cultures can be regulated by muscle activity
      post-translationally. Inhibition of thiol oxidoreductase activity decreases
      expression of all active AChE forms. Likewise, primary quail myotubes transfected
      with protein disulfide isomerase (PDI) short hairpin RNAs showed a significant
      decrease of both the intracellular pool of all collagen-tailed AChE forms and
      cell surface AChE clusters. Conversely, overexpression of PDI, endoplasmic
      reticulum protein 72, or calnexin in muscle cells enhanced expression of all
      collagen-tailed AChE forms. Overexpression of PDI had the most dramatic effect
      with a 100% increase in the intracellular ColQ-AChE pool and cell surface enzyme
      activity. Moreover, the levels of PDI are regulated by muscle activity and
      correlate with the levels of ColQ-AChE and AChE tetramers. Finally, we
      demonstrate that PDI interacts directly with AChE intracellularly. These results
      show that collagen-tailed AChE form levels induced by muscle activity can be
      regulated by molecular chaperones and suggest that newly synthesized exportable
      proteins may compete for chaperone assistance during the folding process.

PMID- 19758987
TI  - AIPL1, a protein associated with childhood blindness, interacts with alpha
      subunit of rod phosphodiesterase (PDE6) and is essential for its proper assembly.
AB  - Mutations in the gene coding for AIPL1 cause Leber congenital amaurosis (LCA), a
      severe form of childhood blindness. The severity in disease is reflected in the
      complete loss of vision and rapid photoreceptor degeneration in the retinas of
      mice deficient in AIPL1. Our previous observations suggest that rod photoreceptor
      degeneration in retinas lacking AIPL1 is due to the massive reduction in levels
      of rod cGMP phosphodiesterase (PDE6) subunits (alpha, beta, and gamma). To date,
      the crucial link between AIPL1 and the stability of PDE6 subunits is not known.
      In this study using ex vivo pulse label analysis, we demonstrate that AIPL1 is
      not involved in the synthesis of PDE6 subunits. However, ex vivo pulse-chase
      analysis clearly shows that in the absence of AIPL1, rod PDE6 subunits are
      rapidly degraded by proteasomes. We further demonstrate that this rapid
      degradation of PDE6 is due to the essential role of AIPL1 in the proper assembly
      of synthesized individual PDE6 subunits. In addition, using a novel monoclonal
      antibody generated against AIPL1, we show that the catalytic subunit (alpha) of
      PDE6 associates with AIPL1 in retinal extracts. Our studies establish that AIPL1
      interacts with the catalytic subunit (alpha) of PDE6 and is needed for the proper
      assembly of functional rod PDE6 subunits.

PMID- 19758988
TI  - Effect of anaplerotic fluxes and amino acid availability on hepatic
      lipoapoptosis.
AB  - To identify metabolic pathways involved in hepatic lipoapoptosis, metabolic flux
      analysis using [U-(13)C(5)]glutamine as an isotopic tracer was applied to
      quantify phenotypic changes in H4IIEC3 hepatoma cells treated with either
      palmitate alone (PA-cells) or both palmitate and oleate in combination (PA/OA
      cells). Our results indicate that palmitate inhibited glycolysis and lactate
      dehydrogenase fluxes while activating citric acid cycle (CAC) flux and glutamine
      uptake. This decoupling of glycolysis and CAC fluxes occurred during the period
      following palmitate exposure but preceding the onset of apoptosis. Oleate co
      treatment restored most fluxes to their control levels, resulting in steatotic
      lipid accumulation while preventing apoptosis. In addition, palmitate strongly
      increased the cytosolic NAD(+)/NADH ratio, whereas oleate co-treatment had the
      opposite effect on cellular redox. We next examined the influence of amino acids
      on these free fatty acid-induced phenotypic changes. Increased medium amino acids
      enhanced reactive oxygen species (ROS) generation and apoptosis in PA-cells but
      not in PA/OA-cells. Overloading the medium with non-essential amino acids induced
      apoptosis, but essential amino acid overloading partially ameliorated apoptosis.
      Glutamate was the most effective single amino acid in promoting ROS. Amino acid
      overloading also increased cellular palmitoyl-ceramide; however, ceramide
      synthesis inhibitors had no effect on measurable indicators of apoptosis. Our
      results indicate that free fatty acid-induced ROS generation and apoptosis are
      accompanied by the decoupling of glycolysis and CAC fluxes leading to abnormal
      cytosolic redox states. Amino acids play a modulatory role in these processes via
      a mechanism that does not involve ceramide accumulation.

PMID- 19758989
TI  - Involvement of ionizable groups in catalysis of human liver glycolate oxidase.
AB  - Glycolate oxidase is a flavin-dependent, peroxisomal enzyme that oxidizes alpha
      hydroxy acids to the corresponding alpha-keto acids, with reduction of oxygen to
      H(2)O(2). In plants, the enzyme participates in photorespiration. In humans, it
      is a potential drug target for treatment of primary hyperoxaluria, a genetic
      disorder where overproduction of oxalate results in the formation of kidney
      stones. In this study, steady-state and pre-steady-state kinetic approaches have
      been used to determine how pH affects the kinetic steps of the catalytic
      mechanism of human glycolate oxidase. The enzyme showed a Ping-Pong Bi-Bi kinetic
      mechanism between pH 6.0 and 10.0. Both the overall turnover of the enzyme
      (k(cat)) and the rate constant for anaerobic substrate reduction of the flavin
      were pH-independent at pH values above 7.0 and decreased slightly at lower pH,
      suggesting the involvement of an unprotonated group acting as a base in the
      chemical step of glycolate oxidation. The second-order rate constant for capture
      of glycolate (k(cat)/K(glycolate)) and the K(d)((app)) for the formation of the
      enzyme-substrate complex suggested the presence of a protonated group with
      apparent pK(a) of 8.5 participating in substrate binding. The k(cat)/K(oxygen)
      values were an order of magnitude faster when a group with pK(a) of 6.8 was
      unprotonated. These results are discussed in the context of the available three
      dimensional structure of GOX.

PMID- 19758990
TI  - Probing the catalytic sites and activation mechanism of photoreceptor
      phosphodiesterase using radiolabeled phosphodiesterase inhibitors.
AB  - Retinal photoreceptor phosphodiesterase (PDE6) is unique among the
      phosphodiesterase enzyme family not only for its catalytic heterodimer but also
      for its regulatory gamma-subunits (Pgamma) whose inhibitory action is released
      upon binding to the G-protein transducin. It is generally assumed that during
      visual excitation both catalytic sites are relieved of Pgamma inhibition upon
      binding of two activated transducin molecules. Because PDE6 shares structural and
      pharmacological similarities with PDE5, we utilized radiolabeled PDE5 inhibitors
      to probe the catalytic sites of PDE6. The membrane filtration assay we used to
      quantify [(3)H]vardenafil binding to PDE6 required histone II-AS to stabilize
      drug binding to the active site. Under these conditions, [(3)H]vardenafil binds
      stoichiometrically to both the alpha- and beta-subunits of the activated PDE6
      heterodimer. [(3)H]vardenafil fails to bind to either the PDE6 holoenzyme or the
      PDE6 catalytic dimer reconstituted with Pgamma, consistent with Pgamma blocking
      access to the drug-binding sites. Following transducin activation of membrane
      associated PDE6 holoenzyme, [(3)H]vardenafil binding increases in proportion to
      the extent of PDE6 activation. Both [(3)H]vardenafil binding and hydrolytic
      activity of transducin-activated PDE6 fail to exceed 50% of the value for the
      PDE6 catalytic dimer. However, adding a 1000-fold excess of activated transducin
      can stimulate the hydrolytic activity of PDE6 to its maximum extent. These
      results demonstrate that both subunits of the PDE6 heterodimer are able to bind
      ligands to the enzyme active site. Furthermore, transducin relieves Pgamma
      inhibition of PDE6 in a biphasic manner, with only one-half of the maximum PDE6
      activity efficiently attained during visual excitation.

PMID- 19758991
TI  - Hepatic autophagy is suppressed in the presence of insulin resistance and
      hyperinsulinemia: inhibition of FoxO1-dependent expression of key autophagy genes
      by insulin.
AB  - Autophagy is essential for maintaining both survival and health of cells.
      Autophagy is normally suppressed by amino acids and insulin. It is unclear what
      happens to the autophagy activity in the presence of insulin resistance and
      hyperinsulinemia. In this study, we examined the autophagy activity in the
      presence of insulin resistance and hyperinsulinemia and the associated mechanism.
      Insulin resistance and hyperinsulinemia were induced in mice by a high fat diet,
      followed by measurements of autophagy markers. Our results show that autophagy
      was suppressed in the livers of mice with insulin resistance and
      hyperinsulinemia. Transcript levels of some key autophagy genes were also
      suppressed in the presence of insulin resistance and hyperinsulinemia.
      Conversely, autophagy activity was increased in the livers of mice with
      streptozotocin-induced insulin deficiency. Levels of vps34, atg12, and gabarapl1
      transcripts were elevated in the livers of mice with insulin deficiency. To study
      the mechanism, autophagy was induced by nutrient deprivation or glucagon in
      cultured hepatocytes in the presence or absence of insulin. Autophagy activity
      and transcript levels of vps34, atg12, and gabarapl1 genes were reduced by
      insulin. The effect of insulin was largely prevented by overexpression of the
      constitutive nuclear form of FoxO1. Importantly, autophagy of mitochondria
      (mitophagy) in cultured cells was suppressed by insulin in the presence of
      insulin resistance. Together, our results show that autophagy activity and
      expression of some key autophagy genes were suppressed in the presence of insulin
      resistance and hyperinsulinemia. Insulin suppression of autophagy involves FoxO1
      mediated transcription of key autophagy genes.

PMID- 19758992
TI  - Transition States.

PMID- 19758993
TI  - Ligand binding turns moth pheromone-binding protein into a pH sensor: effect on
      the Antheraea polyphemus PBP1 conformation.
AB  - In moths, pheromone-binding proteins (PBPs) are responsible for the transport of
      the hydrophobic pheromones to the membrane-bound receptors across the aqueous
      sensillar lymph. We report here that recombinant Antheraea polyphemus PBP1
      (ApolPBP1) picks up hydrophobic molecule(s) endogenous to the Escherichia coli
      expression host that keeps the protein in the "open" (bound) conformation at high
      pH but switches to the "closed" (free) conformation at low pH. This finding has
      bearing on the solution structures of undelipidated lepidopteran moth PBPs
      determined thus far. Picking up a hydrophobic molecule from the host expression
      system could be a common feature for lipid-binding proteins. Thus, delipidation
      is critical for bacterially expressed lipid-binding proteins. We have shown for
      the first time that the delipidated ApolPBP1 exists primarily in the closed form
      at all pH levels. Thus, current views on the pH-induced conformational switch of
      PBPs hold true only for the ligand-bound open conformation of the protein.
      Binding of various ligands to delipidated ApolPBP1 studied by solution NMR
      revealed that the protein in the closed conformation switches to the open
      conformation only at or above pH 6.0 with a protein to ligand stoichiometry of
      approximately 1:1. Mutation of His(70) and His(95) to alanine drives the
      equilibrium toward the open conformation even at low pH for the ligand-bound
      protein by eliminating the histidine-dependent pH-induced conformational switch.
      Thus, the delipidated double mutant can bind ligand even at low pH in contrast to
      the wild type protein as revealed by fluorescence competitive displacement assay
      using 1-aminoanthracene and solution NMR.

PMID- 19758994
TI  - Factor VIII-von Willebrand factor complex inhibits osteoclastogenesis and
      controls cell survival.
AB  - Factor VIII-von Willebrand factor (FVIII.vWF) complex, a molecule involved in
      coagulation, can be physically associated with osteoprotegerin (OPG). OPG is an
      anti-osteoclastic protein and a soluble receptor for the proapoptotic protein
      TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), suggesting a
      potential role of FVIII.vWF complex in bone and cancer biology. We, thus,
      assessed the effects of FVIII.vWF complex on osteoclastogenesis and cell
      survival. We first evidenced that FVIII.vWF complex inhibited RANKL-induced
      osteoclastogenesis and enhanced the inhibitory effect of OPG. Interestingly, we
      revealed by surface plasmon resonance that FVIII.vWF complex bound to RANKL,
      whereas recombinant FVIII and vWF did not. By modeling, we showed that the OPG
      binding domain to the A1 domain of vWF was closely located and partially
      overlapped to its binding site to RANKL. Then, we demonstrated that FVIII.vWF
      complex cancelled the inhibitory activity of OPG on TRAIL-induced apoptosis and
      characterized interactions between these molecules. The present work evidenced a
      direct activity of FVIII.vWF complex on osteoclasts and on induced cell
      apoptosis, pointing out its potential involvement in physiological bone
      remodeling or in bone damages associated with severe hemophilia and cancer
      development.

PMID- 19758995
TI  - Crystal structure of a mucus-binding protein repeat reveals an unexpected
      functional immunoglobulin binding activity.
AB  - Lactobacillus reuteri mucus-binding protein (MUB) is a cell-surface protein that
      is involved in bacterial interaction with mucus and colonization of the digestive
      tract. The 353-kDa mature protein is representative of a broadly important class
      of adhesins that have remained relatively poorly characterized due to their large
      size and highly modular nature. MUB contains two different types of repeats (Mub1
      and Mub2) present in six and eight copies, respectively, and shown to be
      responsible for the adherence to intestinal mucus. Here we report the 1.8-A
      resolution crystal structure of a type 2 Mub repeat (184 amino acids) comprising
      two structurally related domains resembling the functional repeat found in a
      family of immunoglobulin (Ig)-binding proteins. The N-terminal domain bears
      striking structural similarity to the repeat unit of Protein L (PpL) from
      Peptostreptococcus magnus, suggesting binding in a non-immune Fab-dependent
      manner. A distorted PpL-like fold is also seen in the C-terminal domain. As with
      PpL, Mub repeats were able to interact in vitro with a large repertoire of
      mammalian Igs, including secretory IgA. This hitherto undetected activity is
      consistent with the current model that antibody responses against commensal flora
      are of broad specificity and low affinity.

PMID- 19758996
TI  - Caspase-9 activation by the apoptosome is not required for fas-mediated apoptosis
      in type II Jurkat cells.
AB  - Activation of executioner caspases during receptor-mediated apoptosis in type II
      cells requires the engagement of the mitochondrial apoptotic pathway. Although it
      is well established that recruitment of mitochondria in this context involves the
      cleavage of Bid to truncated Bid (tBid), the precise post-mitochondrial signaling
      responsible for executioner caspase activation is controversial. Here, we used
      distinct clones of type II Jurkat T-lymphocytes in which the mitochondrial
      apoptotic pathway had been inhibited to investigate the molecular requirements
      necessary for Fas-induced apoptosis. Cells overexpressing either Bcl-2 or Bcl
      x(L) were protected from apoptosis induced by agonistic anti-Fas antibody. By
      comparison, Apaf-1-deficient Jurkat cells were sensitive to anti-Fas, exhibiting
      Bid cleavage, Bak activation, the release of cytochrome c and Smac, and
      activation of executioner caspase-3. Inhibiting downstream caspase activation
      with the pharmacological inhibitor Z-DEVD-fmk or by expressing the BIR1/BIR2
      domains of X-linked inhibitor of apoptosis protein (XIAP) decreased all anti-Fas
      induced apoptotic changes. Additionally, pretreatment of Bcl-x(L)-overexpressing
      cells with a Smac mimetic sensitized these cells to Fas-induced apoptosis.
      Combined, our findings strongly suggest that Fas-mediated activation of
      executioner caspases and induction of apoptosis do not depend on apoptosome
      mediated caspase-9 activation in prototypical type II cells.

PMID- 19758997
TI  - Human BAMBI cooperates with Smad7 to inhibit transforming growth factor-beta
      signaling.
AB  - Transforming growth factor beta (TGF-beta) and related growth factors are
      essential regulators of embryogenesis and tissue homeostasis. The signaling
      pathways mediated by their receptors and Smad proteins are precisely modulated by
      various means. Xenopus BAMBI (bone morphogenic protein (BMP) and activin membrane
      bound inhibitor) has been shown to function as a general negative regulator of
      TGF-beta/BMP/activin signaling. Here, we provide evidence that human BAMBI
      (hBAMBI), like its Xenopus homolog, inhibits TGF-beta- and BMP-mediated
      transcriptional responses as well as TGF-beta-induced R-Smad phosphorylation and
      cell growth arrest, whereas knockdown of endogenous BAMBI enhances the TGF-beta
      induced reporter expression. Mechanistically, in addition to interfering with the
      complex formation between the type I and type II receptors, hBAMBI cooperates
      with Smad7 to inhibit TGF-beta signaling. hBAMBI forms a ternary complex with
      Smad7 and the TGF-beta type I receptor ALK5/TbetaRI and inhibits the interaction
      between ALK5/TbetaRI and Smad3, thus impairing Smad3 activation. These findings
      provide a novel insight to understand the molecular mechanism underlying the
      inhibitory effect of BAMBI on TGF-beta signaling.

PMID- 19758998
TI  - Hetero-oligomerization of CCR2, CCR5, and CXCR4 and the protean effects of
      "selective" antagonists.
AB  - Chemokine receptors constitute an attractive family of drug targets in the frame
      of inflammatory diseases. However, targeting specific chemokine receptors may be
      complicated by their ability to form dimers or higher order oligomers. Using a
      combination of luminescence complementation and bioluminescence resonance energy
      transfer assays, we demonstrate for the first time the existence of hetero
      oligomeric complexes composed of at least three chemokine receptors (CCR2, CCR5,
      and CXCR4). We show in T cells and monocytes that negative binding cooperativity
      takes place between the binding pockets of these receptors, demonstrating their
      functional interaction in leukocytes. We also show that specific antagonists of
      one receptor (TAK-779 or AMD3100) lead to functional cross-inhibition of the
      others. Finally, using the air pouch model in mice, we show that the CCR2 and
      CCR5 antagonist TAK-779 inhibits cell recruitment promoted by the CXCR4 agonist
      SDF-1 alpha, demonstrating that cross-inhibition by antagonists also occurs in
      vivo. Thus, antagonists of the therapeutically important chemokine receptors
      regulate the functional properties of other receptors to which they do not bind
      directly with important implications for the use of these agents in vivo.

PMID- 19758999
TI  - Dynein dysfunction induces endocytic pathology accompanied by an increase in Rab
      GTPases: a potential mechanism underlying age-dependent endocytic dysfunction.
AB  - Growing evidence suggests that endocytic dysfunction is intimately involved in
      early stage Alzheimer disease pathology, such as the accumulation of beta-amyloid
      precursor protein in enlarged early endosomes. However, it remains unclear how
      endocytic dysfunction is induced in an age-dependent manner. Cytoplasmic dynein,
      a microtubule-based motor protein, interacts with another microtubule-associated
      protein, dynactin. The resulting dynein-dynactin complex mediates minus end
      directed vesicle transport, including endosome trafficking. We have previously
      shown that the interaction between dynein-dynactin complexes is clearly
      attenuated in aged monkey brains, suggesting that dynein-mediated transport
      dysfunction exists in aged brains. Our immunohistochemical analyses revealed that
      age-dependent endocytic pathology was accompanied by an increase in Rab GTPases
      in aged monkey brains. Here, we demonstrated that siRNA-induced dynein
      dysfunction reproduced the endocytic pathology accompanied by increased Rab
      GTPases seen in aged monkey brains and significantly disrupted exosome release.
      Moreover, it also resulted in endosomal beta-amyloid precursor protein
      accumulation characterized by increased beta-site cleavage. These findings
      suggest that dynein dysfunction may underlie age-dependent endocytic dysfunction
      via the up-regulation of Rab GTPases. In addition, this vicious circle may worsen
      endocytic dysfunction, ultimately leading to Alzheimer disease pathology.

PMID- 19759000
TI  - Isolation and characterization of patient-derived, toxic, high mass amyloid beta
      protein (Abeta) assembly from Alzheimer disease brains.
AB  - Amyloid beta-protein (Abeta) assemblies are thought to play primary roles in
      Alzheimer disease (AD). They are considered to acquire surface tertiary
      structures, not present in physiologic monomers, that are responsible for
      exerting toxicity, probably through abnormal interactions with their target(s).
      Therefore, Abeta assemblies having distinct surface tertiary structures should
      cause neurotoxicity through distinct mechanisms. Aiming to clarify the molecular
      basis of neuronal loss, which is a central phenotype in neurodegenerative
      diseases such as AD, we report here the selective immunoisolation of neurotoxic
      10-15-nm spherical Abeta assemblies termed native amylospheroids (native ASPDs)
      from AD and dementia with Lewy bodies brains, using ASPD tertiary structure
      dependent antibodies. In AD patients, the amount of native ASPDs was correlated
      with the pathologic severity of disease. Native ASPDs are anti-pan oligomer A11
      antibody-negative, high mass (>100 kDa) assemblies that induce degeneration
      particularly of mature neurons, including those of human origin, in vitro.
      Importantly, their immunospecificity strongly suggests that native ASPDs have a
      distinct surface tertiary structure from other reported assemblies such as
      dimers, Abeta-derived diffusible ligands, and A11-positive assemblies. Only ASPD
      tertiary structure-dependent antibodies could block ASPD-induced
      neurodegeneration. ASPDs bind presynaptic target(s) on mature neurons and have a
      mode of toxicity different from those of other assemblies, which have been
      reported to exert their toxicity through binding postsynaptic targets and
      probably perturbing glutamatergic synaptic transmission. Thus, our findings
      indicate that native ASPDs with a distinct toxic surface induce neuronal loss
      through a different mechanism from other Abeta assemblies.

PMID- 19759001
TI  - Molecular basis of reduced pyridoxine 5'-phosphate oxidase catalytic activity in
      neonatal epileptic encephalopathy disorder.
AB  - Mutations in pyridoxine 5'-phosphate oxidase are known to cause neonatal
      epileptic encephalopathy. This disorder has no cure or effective treatment and is
      often fatal. Pyridoxine 5'-phosphate oxidase catalyzes the oxidation of
      pyridoxine 5'-phosphate to pyridoxal 5'-phosphate, the active cofactor form of
      vitamin B(6) required by more than 140 different catalytic activities, including
      enzymes involved in amino acid metabolism and biosynthesis of neurotransmitters.
      Our aim is to elucidate the mechanism by which a homozygous missense mutation
      (R229W) in the oxidase, linked to neonatal epileptic encephalopathy, leads to
      reduced oxidase activity. The R229W variant is approximately 850-fold less
      efficient than the wild-type enzyme due to an approximately 192-fold decrease in
      pyridoxine 5'-phosphate affinity and an approximately 4.5-fold decrease in
      catalytic activity. There is also an approximately 50-fold reduction in the
      affinity of the R229W variant for the FMN cofactor. A 2.5 A crystal structure of
      the R229W variant shows that the substitution of Arg-229 at the FMN binding site
      has led to a loss of hydrogen-bond and/or salt-bridge interactions between FMN
      and Arg-229 and Ser-175. Additionally, the mutation has led to an alteration of
      the configuration of a beta-strand-loop-beta-strand structure at the active site,
      resulting in loss of two critical hydrogen-bond interactions involving residues
      His-227 and Arg-225, which are important for substrate binding and orientation
      for catalysis. These results provide a molecular basis for the phenotype
      associated with the R229W mutation, as well as providing a foundation for
      understanding the pathophysiological consequences of pyridoxine 5'-phosphate
      oxidase mutations.

PMID- 19759002
TI  - The molecular chaperone Hsp90 modulates intermediate steps of amyloid assembly of
      the Parkinson-related protein alpha-synuclein.
AB  - Alpha-synuclein is an intrinsically unstructured protein that binds to membranes,
      forms fibrils, and is involved in neurodegeneration. We used a reconstituted in
      vitro system to show that the molecular chaperone Hsp90 influenced alpha
      synuclein vesicle binding and amyloid fibril formation, two processes that are
      tightly coupled to alpha-synuclein folding. Binding of Hsp90 to monomeric alpha
      synuclein occurred in the low micromolar range, involving regions of alpha
      synuclein that are critical for vesicle binding and amyloidogenesis. As a
      consequence, both processes were affected. In the absence of ATP, the
      accumulation of non-amyloid alpha-synuclein oligomers prevailed over fibril
      formation, whereas ATP favored fibril growth. This suggests that Hsp90 modulates
      the assembly of alpha-synuclein in an ATP-dependent manner. We propose that Hsp90
      affects these folding processes by restricting conformational fluctuations of
      alpha-synuclein.

PMID- 19759003
TI  - A slow ATP-induced conformational change limits the rate of DNA binding but not
      the rate of beta clamp binding by the escherichia coli gamma complex clamp
      loader.
AB  - In Escherichia coli, the gamma complex clamp loader loads the beta-sliding clamp
      onto DNA. The beta clamp tethers DNA polymerase III to DNA and enhances the
      efficiency of replication by increasing the processivity of DNA synthesis. In the
      presence of ATP, gamma complex binds beta and DNA to form a ternary complex.
      Binding to primed template DNA triggers gamma complex to hydrolyze ATP and
      release the clamp onto DNA. Here, we investigated the kinetics of forming a
      ternary complex by measuring rates of gamma complex binding beta and DNA. A
      fluorescence intensity-based beta binding assay was developed in which the
      fluorescence of pyrene covalently attached to beta increases when bound by gamma
      complex. Using this assay, an association rate constant of 2.3 x 10(7) m(-1) s(
      1) for gamma complex binding beta was determined. The rate of beta binding was
      the same in experiments in which gamma complex was preincubated with ATP before
      adding beta or added directly to beta and ATP. In contrast, when gamma complex is
      preincubated with ATP, DNA binding is faster than when gamma complex is added to
      DNA and ATP at the same time. Slow DNA binding in the absence of ATP
      preincubation is the result of a rate-limiting ATP-induced conformational change.
      Our results strongly suggest that the ATP-induced conformational changes that
      promote beta binding and DNA binding differ. The slow ATP-induced conformational
      change that precedes DNA binding may provide a kinetic preference for gamma
      complex to bind beta before DNA during the clamp loading reaction cycle.

PMID- 19759004
TI  - Cooperative transcriptional regulation of the essential pancreatic islet gene
      NeuroD1 (beta2) by Nkx2.2 and neurogenin 3.
AB  - Nkx2.2 and NeuroD1 are two critical regulators of pancreatic beta cell
      development. Nkx2.2 is a homeodomain transcription factor that is essential for
      islet cell type specification and mature beta cell function. NeuroD1 is a basic
      helix-loop-helix transcription factor that is critical for islet beta cell
      maturation and maintenance. Although both proteins influence beta cell
      development directly downstream of the endocrine progenitor factor, neurogenin3
      (Ngn3), a connection between the two proteins in the regulation of beta cell fate
      and function has yet to be established. In this study, we demonstrate that Nkx2.2
      transcriptional activity is required to facilitate the activation of NeuroD1 by
      Ngn3. Furthermore, Nkx2.2 is necessary to maintain high levels of NeuroD1
      expression in developing mouse and zebrafish islets and in mature beta cells.
      Interestingly, Nkx2.2 regulates NeuroD1 through two independent promoter
      elements, one that is bound and activated directly by Nkx2.2 and one that appears
      to be regulated by Nkx2.2 through an indirect mechanism. Together, these findings
      suggest that Nkx2.2 coordinately activates NeuroD1 with Ngn3 within the endocrine
      progenitor cell and also plays a role in the maintenance of NeuroD1 expression to
      regulate beta cell function in the mature islet. Collectively, these findings
      further define the conserved regulatory networks involved in islet beta cell
      formation and function.

PMID- 19759005
TI  - Nucleotide binding by Lhs1p is essential for its nucleotide exchange activity and
      for function in vivo.
AB  - Protein translocation and folding in the endoplasmic reticulum of Saccharomyces
      cerevisiae involves two distinct Hsp70 chaperones, Lhs1p and Kar2p. Both proteins
      have the characteristic domain structure of the Hsp70 family consisting of a
      conserved N-terminal nucleotide binding domain and a C-terminal substrate binding
      domain. Kar2p is a canonical Hsp70 whose substrate binding activity is regulated
      by cochaperones that promote either ATP hydrolysis or nucleotide exchange. Lhs1p
      is a member of the Grp170/Lhs1p subfamily of Hsp70s and was previously shown to
      function as a nucleotide exchange factor (NEF) for Kar2p. Here we show that in
      addition to this NEF activity, Lhs1p can function as a holdase that prevents
      protein aggregation in vitro. Analysis of the nucleotide requirement of these
      functions demonstrates that nucleotide binding to Lhs1p stimulates the
      interaction with Kar2p and is essential for NEF activity. In contrast, Lhs1p
      holdase activity is nucleotide-independent and unaffected by mutations that
      interfere with ATP binding and NEF activity. In vivo, these mutants show severe
      protein translocation defects and are unable to support growth despite the
      presence of a second Kar2p-specific NEF, Sil1p. Thus, Lhs1p-dependent nucleotide
      exchange activity is vital for ER protein biogenesis in vivo.

PMID- 19759006
TI  - Selective activation of the p38 MAPK pathway by synthetic monophosphoryl lipid A.
AB  - TLR4 stimulation by lipopolysaccharide can cause both MAL/MyD88- and TRAM/TRIF
      (Toll IL-1 receptor domain-containing adaptor-inducing IFNbeta)-dependent
      signaling events. Monophosphoryl lipid A (MPLA), a low toxicity derivative of
      endotoxic lipopolysaccharide, enhances antibody responses, T cell expansion, and
      recall responses against antigens without causing excessive inflammatory side
      effects. Previously, we proposed that TRIF-biased activation of TLR4 by MPLA is
      responsible for its reduced toxicity while retaining potent adjuvant effects.
      However, some TRIF-associated genes, such as MCP-1, are only weakly expressed,
      and some MyD88-associated inflammatory and anti-inflammatory cytokines, such as
      tumor necrosis factor alpha and interleukin-10, are strongly activated after MPLA
      stimulation despite weak NF-kappaB but strong IRF3 activation. We now report that
      synthetic derivatives of MPLA retained TRIF bias as compared with synthetic
      diphosphoryl lipid A, indicating a change in a single phosphoryl group is
      sufficient for TRIF-biased TLR4 stimulation. We extend our previous observations
      by showing that sMLA induces strong p38 MAPK but weak JNK activation, resulting
      in high IP-10 (interferon-inducible protein 10), tumor necrosis factor alpha, and
      interleukin-10 but low MCP-1 transcript levels. Results of this study identify a
      novel biochemical mechanism for regulation of sMLA-induced gene expression.

PMID- 19759007
TI  - C-terminal residues regulate localization and function of the antiapoptotic
      protein Bfl-1.
AB  - Unlike other antiapoptotic members of the Bcl-2 family, Bfl-1 does not contain a
      well defined C-terminal transmembrane domain, and whether the C-terminal tail of
      Bfl-1 functions as a membrane anchor is not yet clearly established. The
      molecular modeling study of the full-length Bfl-1 performed within this work
      suggests that Bfl-1 may co-exist in two distinct conformational states: one in
      which its C-terminal helix alpha9 is inserted in the hydrophobic groove formed by
      the BH1-3 domains of Bfl-1 and one with its C terminus. Parallel analysis of the
      subcellular localization of Bfl-1 indicates that even if Bfl-1 may co-exist in
      two distinct conformational states, most of the endogenous protein is tightly
      associated with the mitochondria by its C terminus in both healthy and apoptotic
      peripheral blood lymphocytes as well as in malignant B cell lines. However, the
      helix alpha9 of Bfl-1, and therefore the binding of Bfl-1 to mitochondria, is not
      absolutely required for the antiapoptotic activity of Bfl-1. A particular feature
      of Bfl-1 is the amphipathic character of its C-terminal helix alpha9. Our data
      clearly indicate that this property of helix alpha9 is required for the anchorage
      of Bfl-1 to the mitochondria but also regulates the antiapoptotic function Bfl-1.

PMID- 19759008
TI  - Characterization of a disease-associated mutation affecting a putative splicing
      regulatory element in intron 6b of the cystic fibrosis transmembrane conductance
      regulator (CFTR) gene.
AB  - Cystic fibrosis (CF) is a common recessive disorder caused by >1600 mutations in
      the CF transmembrane conductance regulator (CFTR) gene. About 13% of CFTR
      mutations are classified as "splicing mutations," but for almost 40% of these,
      their role in affecting the pre-mRNA splicing of the gene is not yet defined. In
      this work, we describe a new splicing mutation detected in three unrelated
      Italian CF patients. By DNA analyses and mRNA studies, we identified the c.1002
      1110_1113delTAAG mutation localized in intron 6b of the CFTR gene. At the mRNA
      level, this mutation creates an aberrant inclusion of a sequence of 101
      nucleotides between exons 6b and 7. This sequence corresponds to a portion of
      intron 6b and resembles a cryptic exon because it is characterized by an upstream
      ag and a downstream gt sequence, which are most probably recognized as 5'- and 3'
      splice sites by the spliceosome. Through functional analysis of this splicing
      defect, we show that this mutation abolishes the interaction of the splicing
      regulatory protein heterogeneous nuclear ribonucleoprotein A2/B1 with an intronic
      splicing regulatory element and creates a new recognition motif for the SRp75
      splicing factor, causing activation of the cryptic exon. Our results show that
      the c.1002-1110_1113delTAAG mutation creates a new intronic splicing regulatory
      element in intron 6b of the CFTR gene exclusively recognized by SRp75.

PMID- 19759009
TI  - Electrophilic affibodies forming covalent bonds to protein targets.
AB  - Antibody affinity limits sensitivity of detection in many areas of biology and
      medicine. High affinity usually depends on achieving the optimal combination of
      the natural 20 amino acids in the antibody binding site. Here, we investigate the
      effect on recognition of protein targets of placing an unnatural electrophile
      adjacent to the target binding site. We positioned a weak electrophile,
      acrylamide, near the binding site between an affibody, a non-immunoglobulin
      binding scaffold, and its protein target. The proximity between cysteine, lysine,
      or histidine on the target protein drove covalent bond formation to the
      electrophile on the affibody. Covalent bonds did not form to a non-interacting
      point mutant of the target, and there was minimal cross-reactivity with serum,
      cell lysate, or when imaging at the cell surface. Electrophilic affibodies showed
      more stable protein imaging at the surface of mammalian cells, and the
      sensitivity of protein detection in an immunoassay improved by two orders of
      magnitude. Thus electrophilic affibodies combined good specificity with improved
      detection of protein targets.

PMID- 19759010
TI  - Single vesicle millisecond fusion kinetics reveals number of SNARE complexes
      optimal for fast SNARE-mediated membrane fusion.
AB  - SNAREs mediate membrane fusion in intracellular vesicle traffic and neuronal
      exocytosis. Reconstitution of membrane fusion in vitro proved that SNAREs
      constitute the minimal fusion machinery. However, the slow fusion rates observed
      in these systems are incompatible with those required in neurotransmission. Here
      we present a single vesicle fusion assay that records individual SNARE-mediated
      fusion events with millisecond time resolution. Docking and fusion of
      reconstituted synaptobrevin vesicles to target SNARE complex-containing planar
      membranes are distinguished by total internal reflection fluorescence microscopy
      as separate events. Docking and fusion are SNAP-25-dependent, require no Ca(2+),
      and are efficient at room temperature. Analysis of the stochastic data with
      sequential and parallel multi-particle activation models reveals six to nine fast
      activating steps. Of all the tested models, the kinetic model consisting of eight
      parallel reaction rates statistically fits the data best. This might be
      interpreted by fusion sites consisting of eight SNARE complexes that each
      activate in a single rate-limiting step in 8 ms.

PMID- 19759011
TI  - Adenosine-to-inosine genetic recoding is required in the adult stage nervous
      system for coordinated behavior in Drosophila.
AB  - Adenosine deaminases acting on RNA (ADARs) catalyze the deamination of adenosine
      to inosine in double-stranded RNA templates, a process known as RNA editing. In
      Drosophila, multiple ADAR isoforms are generated from a single locus (dAdar) via
      post-transcriptional modifications. Collectively, these isoforms act to edit a
      wide range of transcripts involved in neuronal signaling, as well as the
      precursors of endogenous small interfering RNAs. The phenotypic consequences of a
      loss of dADAR activity have been well characterized and consist of profound
      behavioral defects manifested at the adult stage, including extreme
      uncoordination, seizures, and temperature-sensitive paralysis. However, the
      spatio-temporal requirements of adenosine to inosine editing for correct behavior
      are unclear. Using transgenic RNA interference, we show that network-wide editing
      in the nervous system is required for normal adult locomotion. Regulated
      restoration of editing activity demonstrates that the neuronal requirement of
      dADAR activity has a significant adult stage component. Furthermore we show that
      in relation to behavior there are no observable genetic interactions between
      dAdar and several loci encoding RNA interference components, suggesting that
      editing of neuronal transcripts is the key mode of ADAR activity for normal
      behavior in Drosophila.

PMID- 19759012
TI  - The dexamethasone-induced inhibition of proliferation, migration, and invasion in
      glioma cell lines is antagonized by macrophage migration inhibitory factor (MIF)
      and can be enhanced by specific MIF inhibitors.
AB  - Glioblastomas (GBMs) are the most frequent and malignant brain tumors in adults.
      Glucocorticoids (GCs) are routinely used in the treatment of GBMs for their
      capacity to reduce the tumor-associated edema. Few in vitro studies have
      suggested that GCs inhibit the migration and invasion of GBM cells through the
      induction of MAPK phosphatase 1 (MKP-1). Macrophage migration inhibitory factor
      (MIF), an endogenous GC antagonist is up-regulated in GBMs. Recently, MIF has
      been involved in tumor growth and migration/invasion and specific MIF inhibitors
      have been developed on their capacity to block its enzymatic tautomerase activity
      site. In this study, we characterized several glioma cell lines for their MIF
      production. U373 MG cells were selected for their very low endogenous levels of
      MIF. We showed that dexamethasone inhibits the migration and invasion of U373 MG
      cells, through a glucocorticoid receptor (GR)- dependent inhibition of the ERK1/2
      MAPK pathway. Oppositely, we found that exogenous MIF increases U373 MG migration
      and invasion through the stimulation of the ERK1/2 MAP kinase pathway and that
      this activation is CD74 independent. Finally, we used the Hs 683 glioma cells
      that are resistant to GCs and produce high levels of endogenous MIF, and showed
      that the specific MIF inhibitor ISO-1 could restore dexamethasone sensitivity in
      these cells. Collectively, our results indicate an intricate pathway between MIF
      expression and GC resistance. They suggest that MIF inhibitors could increase the
      response of GBMs to corticotherapy.

PMID- 19759013
TI  - Bax1 is a novel endonuclease: implications for archaeal nucleotide excision
      repair.
AB  - The helicases XPB and XPD are part of the TFIIH complex, which mediates
      transcription initiation as well as eukaryotic nucleotide excision repair (NER).
      Although there is no TFIIH complex present in archaea, most species contain both
      XPB and XPD and serve as a model for their eukaryotic homologs. Recently, a novel
      binding partner for XPB, Bax1 (binds archeal XPB), was identified in archaea. To
      gain insights into its role in NER, Bax1 from Thermoplasma acidophilum was
      characterized. We identified Bax1 as a novel Mg(2+)-dependent structure-specific
      endonuclease recognizing DNA containing a 3' overhang. Incision assays conducted
      with DNA substrates providing different lengths of the 3' overhang indicate that
      Bax1 specifically incises DNA in the single-stranded region of the 3' overhang 4
      6 nucleotides to the single-stranded DNA/double-stranded DNA junction and thus is
      a structure-specific and not a sequence-specific endonuclease. In contrast, no
      incision was detected in the presence of a 5' overhang, double-stranded DNA, or
      DNA containing few unpaired nucleotides forming a bubble. Several Bax1 variants
      were generated based on multiple sequence alignments and examined with respect to
      their ability to perform the incision reaction. Residues Glu-124, Asp-132, Tyr
      152, and Glu-155 show a dramatic reduction in incision activity, indicating a
      pivotal role in catalysis. Interestingly, Bax1 does not exhibit any incision
      activity in the presence of XPB, thus suggesting a role in NER in which the
      endonuclease activity is tightly regulated until the damage has been recognized
      and verified prior to the incision event.

PMID- 19759014
TI  - Demonstration and characterization of the heterodimerization of ZnT5 and ZnT6 in
      the early secretory pathway.
AB  - The majority of CDF/ZnT zinc transporters form homo-oligomers. However, ZnT5,
      ZnT6, and their orthologues form hetero-oligomers in the early secretory pathway
      where they load zinc onto zinc-requiring enzymes and maintain secretory pathway
      functions. The details of this hetero-oligomerization remain to be elucidated,
      and much more is known about homo-oligomerization that occurs in other CDF/ZnT
      family proteins. Here, we addressed this issue using co-immunoprecipitation
      experiments, mutagenesis, and chimera studies of hZnT5 and hZnT6 in chicken DT40
      cells deficient in ZnT5, ZnT6, and ZnT7 proteins. We found that hZnT5 and hZnT6
      combine to form heterodimers but do not form complexes larger than heterodimers.
      Mutagenesis of hZnT6 indicated that the sites present in transmembrane domains II
      and V in which many CDF/ZnT proteins have conserved hydrophilic amino acid
      residues are not involved in zinc binding of hZnT6, although they are required
      for zinc transport in other CDF/ZnT family homo-oligomers. We also found that the
      long N-terminal half of hZnT5 is not necessary for its functional interaction
      with hZnT6, whereas the cytosolic C-terminal tail of hZnT5 is important in
      determining hZnT6 as a partner molecule for heterodimer formation. In DT40 cells,
      cZnT5 variant lacking the N-terminal half was endogenously induced during periods
      of endoplasmic reticulum stress and so seemed to function to supply zinc to zinc
      requiring enzymes under these conditions. The results outlined here provide new
      information about the mechanism of action through heterodimerization of CDF/ZnT
      proteins that function in the early secretory pathway.

PMID- 19759015
TI  - Structure and interdomain dynamics of apoptosis-associated speck-like protein
      containing a CARD (ASC).
AB  - The human protein ASC is a key mediator in apoptosis and inflammation. Through
      its two death domains (pyrin and CARD) ASC interacts with cell death
      executioners, acts as an essential adapter for inflammasome integrity, and
      oligomerizes into functional supramolecular assemblies. However, these functions
      are not understood at the structural-dynamic level. This study reports the
      solution structure and interdomain dynamics of full-length ASC. The pyrin and
      CARD domains are structurally independent six-helix bundle motifs connected by a
      23-residue linker. The CARD structure reveals two distinctive characteristics;
      helix 1 is not fragmented as in all other known CARDs, and its electrostatic
      surface shows a uniform distribution of positive and negative charges, whereas
      these are commonly separated into two areas in other death domains. The linker
      adopts residual structure resulting in a back-to-back orientation of the domains,
      which avoids steric interference of each domain with the binding site of the
      other. NMR relaxation experiments show that the linker is flexible despite the
      residual structure. This flexibility could help expand the relative volume
      occupied by each domain, thus increasing the capture radius for effectors. Based
      on the ASC structure, a tentative model is proposed to illustrate how ASC
      oligomerizes via CARD and pyrin homophilic interactions. Moreover, ASC oligomers
      have been analyzed by atomic force microscopy, showing a predominant species of
      disk-like particles of approximately 12-nm diameter and approximately 1-nm
      height. Taken together, these results provide structural insight into the
      behavior of ASC as an adapter molecule.

PMID- 19759016
TI  - Naturally occurring mutations alter the stability of polycystin-1 polycystic
      kidney disease (PKD) domains.
AB  - Mutations in polycystin-1 (PC1) can cause autosomal dominant polycystic kidney
      disease, which is a leading cause of renal failure. The available evidence
      suggests that PC1 acts as a mechanosensor, receiving signals from the primary
      cilia, neighboring cells, and extracellular matrix. PC1 is a large membrane
      protein that has a long N-terminal extracellular region (about 3000 amino acids)
      with a multimodular structure including 16 Ig-like polycystic kidney disease
      (PKD) domains, which are targeted by many naturally occurring missense mutations.
      Nothing is known about the effects of these mutations on the biophysical
      properties of PKD domains. Here we investigate the effects of several naturally
      occurring mutations on the mechanical stability of the first PKD domain of human
      PC1 (HuPKDd1). We found that several missense mutations alter the mechanical
      unfolding pathways of HuPKDd1, resulting in distinct mechanical phenotypes.
      Moreover, we found that these mutations also alter the thermodynamic stability of
      a structurally homologous archaeal PKD domain. Based on these findings, we
      hypothesize that missense mutations may cause autosomal dominant polycystic
      kidney disease by altering the stability of the PC1 ectodomain, thereby
      perturbing its ability to sense mechanical signals.

PMID- 19759017
TI  - DNA polymerase beta substrate specificity: side chain modulation of the "A-rule".
AB  - Apurinic/apyrimidinic (AP) sites are continuously generated in genomic DNA. Left
      unrepaired, AP sites represent noninstructional premutagenic lesions that are
      impediments to DNA synthesis. When DNA polymerases encounter an AP site, they
      generally insert dAMP. This preferential insertion is referred to as the A-rule.
      Crystallographic structures of DNA polymerase (pol) beta, a family X polymerase,
      with active site mismatched nascent base pairs indicate that the templating (i.e.
      coding) base is repositioned outside of the template binding pocket thereby
      diminishing interactions with the incorrect incoming nucleotide. This effectively
      produces an abasic site because the template pocket is devoid of an instructional
      base. However, the template pocket is not empty; an arginine residue (Arg-283)
      occupies the space vacated by the templating nucleotide. In this study, we
      analyze the kinetics of pol beta insertion opposite an AP site and show that the
      preferential incorporation of dAMP is lost with the R283A mutant. The
      crystallographic structures of pol beta bound to gapped DNA with an AP site
      analog (tertrahydrofuran) in the gap (binary complex) and with an incoming
      nonhydrolyzable dATP analog (ternary complex) were solved. These structures
      reveal that binding of the dATP analog induces a closed polymerase conformation,
      an unstable primer terminus, and an upstream shift of the templating residue even
      in the absence of a template base. Thus, dATP insertion opposite an abasic site
      and dATP misinsertions have common features.

PMID- 19759018
TI  - Drosophila RecQ4 has a 3'-5' DNA helicase activity that is essential for
      viability.
AB  - Members of the RecQ family of proteins are highly conserved DNA helicases that
      have important functions in the maintenance of genomic stability. Deficiencies in
      RecQ4 have been linked to human diseases including Rothmund-Thomson, RAPADILINO,
      and Baller-Gerold syndromes, all of which are characterized by developmental
      defects, tumor propensity, and genetic instability. However, there are
      conflicting results shown in the literature regarding the DNA helicase activity
      of RecQ4. We report here the expression of Drosophila melanogaster RecQ4 with a
      baculoviral vector and its purification to near homogeneity. The purified protein
      has a DNA-dependent ATPase activity and is a 3'-5' DNA helicase dependent on
      hydrolysis of ATP. The presence of 5'-adenylyl-beta,gamma-imidodiphosphate
      (AMPPNP), a nonhydrolyzable ATP analog, promotes stable complex formation between
      RecQ4 and single-stranded DNA. Drosophila RecQ4 can also anneal complementary
      single strands; this activity was reduced in the presence of AMPPNP, possibly
      because of the stable protein-DNA complex formed under such conditions. A point
      mutation of the highly conserved lysine residue in the helicase domain, although
      retaining the wild type level of annealing activity, inactivated ATPase and
      helicase activities and eliminated stable complex formation. These results
      suggest that the helicase domain alone is responsible for the DNA unwinding
      action of the Drosophila enzyme. We generated a null recq4 mutant that is
      homozygous lethal, which we used to test the genetic function of the helicase
      dead mutant in flies. Complementation tests showed that the helicase-dead mutant
      recq4 transgenes are incapable of rescuing the null mutation, demonstrating that
      the helicase activity has an essential biological function.

PMID- 19759019
TI  - Integrator3, a partner of single-stranded DNA-binding protein 1, participates in
      the DNA damage response.
AB  - Single-stranded DNA-binding protein 1 (SSB1) plays an important role in the DNA
      damage response and maintenance of genomic stability. Here, by using protein
      affinity purification, we have identified Integrator3 (INT3) as a novel partner
      of SSB1. INT3 forms a complex with SSB1 by constitutively interacting with SSB1
      regardless of DNA damage. However, following DNA damage, along with SSB1, INT3
      relocates to the DNA damage sites and regulates the accumulation of TopBP1 and
      BRCA1 there. Moreover, INT3 controls DNA damage-induced Chk1 activation and
      G(2)/M checkpoint activation. In addition, INT3 is involved in homologous
      recombination repair by regulating Rad51 foci formation following DNA damage.
      Taken together, these results demonstrate that INT3 plays a key role in the DNA
      damage response.

PMID- 19759020
TI  - The clamp loader assembles the beta clamp onto either a 3' or 5' primer terminus:
      the underlying basis favoring 3' loading.
AB  - Clamp loaders assemble sliding clamps onto 3' primed sites for DNA polymerases.
      Clamp loaders are thought to be specific for a 3' primed site, and unable to bind
      a 5' site. We demonstrate here that the Escherichia coli gamma complex clamp
      loader can load the beta clamp onto a 5' primed site, although with at least 20
      fold reduced efficiency relative to loading at a 3' primed site. Preferential
      clamp loading at a 3' site does not appear to be due to DNA binding, as the clamp
      loader forms an avid complex with beta at a 5' site. Preferential loading at a 3'
      versus a 5' site occurs at the ATP hydrolysis step, needed to close the ring
      around DNA. We also address DNA structural features that are recognized for
      preferential loading at a 3' site. Although the single-stranded template strand
      extends in opposite directions from 3' and 5' primed sites, thus making it a
      favorite candidate for distinguishing between 3' and 5' sites, the single-strand
      polarity at a primed template junction does not determine 3' site selection for
      clamp loading. Instead, we find that clamp loader recognition of a 3' site lies
      in the duplex portion of the primed site, not the single-strand portion. We
      present evidence that the beta clamp facilitates its own loading specificity for
      a 3' primed site. Implications to eukaryotic clamp loader complexes are proposed.

PMID- 19759021
TI  - Catabolism of 4-hydroxyacids and 4-hydroxynonenal via 4-hydroxy-4-phosphoacyl
      CoAs.
AB  - 4-Hydroxyacids are products of ubiquitously occurring lipid peroxidation (C(9),
      C(6)) or drugs of abuse (C(4), C(5)). We investigated the catabolism of these
      compounds using a combination of metabolomics and mass isotopomer analysis.
      Livers were perfused with various concentrations of unlabeled and labeled
      saturated 4-hydroxyacids (C(4) to C(11)) or 4-hydroxynonenal. All the compounds
      tested form a new class of acyl-CoA esters, 4-hydroxy-4-phosphoacyl-CoAs,
      characterized by liquid chromatography-tandem mass spectrometry, accurate mass
      spectrometry, and (31)P-NMR. All 4-hydroxyacids with five or more carbons are
      metabolized by two new pathways. The first and major pathway, which involves 4
      hydroxy-4-phosphoacyl-CoAs, leads in six steps to the isomerization of 4
      hydroxyacyl-CoA to 3-hydroxyacyl-CoAs. The latter are intermediates of
      physiological beta-oxidation. The second and minor pathway involves a sequence of
      beta-oxidation, alpha-oxidation, and beta-oxidation steps. In mice deficient in
      succinic semialdehyde dehydrogenase, high plasma concentrations of 4
      hydroxybutyrate result in high concentrations of 4-hydroxy-4-phospho-butyryl-CoA
      in brain and liver. The high concentration of 4-hydroxy-4-phospho-butyryl-CoA may
      be related to the cerebral dysfunction of subjects ingesting 4-hydroxybutyrate
      and to the mental retardation of patients with 4-hydroxybutyric aciduria. Our
      data illustrate the potential of the combination of metabolomics and mass
      isotopomer analysis for pathway discovery.

PMID- 19759022
TI  - Heme transfer to the bacterial cell envelope occurs via a secreted hemophore in
      the Gram-positive pathogen Bacillus anthracis.
AB  - To initiate and sustain an infection in mammals, bacterial pathogens must acquire
      host iron. However, the host's compartmentalization of large amounts of iron in
      heme, which is bound primarily by hemoglobin in red blood cells, acts as a
      barrier to bacterial iron assimilation. Bacillus anthracis, the causative agent
      of the disease anthrax, secretes two NEAT (near iron transporter) proteins, IsdX1
      and IsdX2, which scavenge heme from host hemoglobin and promote growth under low
      iron conditions. The mechanism of heme transfer from these hemophores to the
      bacterial cell is not known. We present evidence that the heme-bound form of
      IsdX1 rapidly and directionally transfers heme to IsdC, a NEAT protein covalently
      attached to the cell wall, as well as to IsdX2. In both cases, the transfer of
      heme is mediated by a physical association between the donor and recipient.
      Unlike Staphylococcus aureus, whose NEAT proteins acquire heme from hemoglobin
      directly at the bacterial surface, B. anthracis secretes IsdX1 to capture heme in
      the extracellular milieu and relies on NEAT-NEAT interactions to deliver the
      bound heme to the envelope via IsdC. Understanding the mechanism of NEAT-mediated
      iron transport into pathogenic Gram-positive bacteria may provide an avenue for
      the development of therapeutics to combat infection.

PMID- 19759023
TI  - CK1alpha plays a central role in mediating MDM2 control of p53 and E2F-1 protein
      stability.
AB  - The ubiquitin ligase murine double minute clone 2 (MDM2) mediates ubiquitination
      and degradation of the tumor suppressor p53. The activation and stabilization of
      p53 by contrast is maintained by enzymes catalyzing p53 phosphorylation and
      acetylation. Casein kinase 1 (CK1) is one such enzyme; it stimulates p53 after
      transforming growth factor-beta treatment, irradiation, or DNA virus infection.
      We analyzed whether CK1 regulates p53 protein stability in unstressed conditions.
      Depletion of CK1 using small interfering RNA or inhibition of CK1 using the
      kinase inhibitor (D4476) activated p53 and destabilized E2F-1, indicating that
      steady-state levels of these proteins are controlled by CK1. Co
      immunoprecipitation of endogenous CK1 with MDM2 occurred in undamaged cells,
      indicating the existence of a stable multiprotein complex, and as such, we
      evaluated whether the MDM2 Nutlin had similar pharmacological properties to the
      CK1 inhibitor D4476. Indeed, D4476 or Nutlin treatments resulted in the same p53
      and E2F-1 steady-state protein level changes, indicating that the MDM2 x CK1
      complex is both a negative regulator of p53 and a positive regulator of E2F-1 in
      undamaged cells. Although the treatment of cells with D4476 resulted in a partial
      p53-dependent growth arrest, the induction of p53-independent apoptosis by D4476
      suggested a critical role for the MDM2 x CK1 complex in maintaining E2F-1 anti
      apoptotic signaling. These data highlighting a pharmacological similarity between
      MDM2 and CK1 small molecule inhibitors and the fact that CK1 and MDM2 form a
      stable complex suggest that the MDM2 x CK1 complex is a component of a genetic
      pathway that co-regulates the stability of the p53 and E2F-1 transcription
      factors.

PMID- 19759024
TI  - Ferredoxin:NADP+ oxidoreductase association with phycocyanin modulates its
      properties.
AB  - In photosynthetic organisms, ferredoxin:NADP(+) oxidoreductase (FNR) is known to
      provide NADPH for CO(2) assimilation, but it also utilizes NADPH to provide
      reduced ferredoxin. The cyanobacterium Synechocystis sp. strain PCC6803 produces
      two FNR isoforms, a small one (FNR(S)) similar to the one found in plant plastids
      and a large one (FNR(L)) that is associated with the phycobilisome, a light
      harvesting complex. Here we show that a mutant lacking FNR(L) exhibits a higher
      NADP(+)/NADPH ratio. We also purified to homogeneity a phycobilisome subcomplex
      comprising FNR(L,) named FNR(L)-PC. The enzymatic activities of FNR(L)-PC were
      compared with those of FNR(S). During NADPH oxidation, FNR(L)-PC exhibits a 30%
      decrease in the Michaelis constant K(m)((NADPH)), and a 70% increase in
      K(m)((ferredoxin)), which is in agreement with its predicted lower activity of
      ferredoxin reduction. During NADP(+) reduction, the FNR(L)-PC shows a 29/43%
      decrease in the rate of single electron transfer from reduced ferredoxin in the
      presence/absence of NADP(+). The increase in K(m)((ferredoxin)) and the rate
      decrease of single reduction are attributed to steric hindrance by the
      phycocyanin moiety of FNR(L)-PC. Both isoforms are capable of catalyzing the
      NADP(+) reduction under multiple turnover conditions. Furthermore, we obtained
      evidence that, under high ionic strength conditions, electron transfer from
      reduced ferredoxin is rate limiting during this process. The differences that we
      observe might not fully explain the in vivo properties of the Synechocystis
      mutants expressing only one of the isoforms. Therefore, we advocate that FNR
      localization and/or substrates availability are essential in vivo.

PMID- 19759025
TI  - WITHDRAWN: TcJAMYC: A bHLH transcription factor that activates paclitaxel
      biosynthetic pathway genes in yew.
AB  - This article was withdrawn by the authors before final publication on October 1,
      2009.

PMID- 19759026
TI  - SAGA and Rpd3 chromatin modification complexes dynamically regulate heat shock
      gene structure and expression.
AB  - The chromatin structure of heat shock protein (HSP)-encoding genes undergoes
      dramatic alterations upon transcriptional induction, including, in extreme cases,
      domain-wide nucleosome disassembly. Here, we use a combination of gene knock-out,
      in situ mutagenesis, chromatin immunoprecipitation, and expression assays to
      investigate the role of histone modification complexes in regulating heat shock
      gene structure and expression in Saccharomyces cerevisiae. Two histone
      acetyltransferases, Gcn5 and Esa1, were found to stimulate HSP gene
      transcription. A detailed chromatin immunoprecipitation analysis of the Gcn5
      containing SAGA complex (signified by Spt3) revealed its presence within the
      promoter of every heat shock factor 1-regulated gene examined. The occupancy of
      SAGA increased substantially upon heat shock, peaking at several HSP promoters
      within 30-45 s of temperature upshift. SAGA was also efficiently recruited to the
      coding regions of certain HSP genes (where its presence mirrored that of pol II),
      although not at others. Robust and rapid recruitment of repressive, Rpd3
      containing histone deacetylase complexes was also seen and at all HSP genes
      examined. A detailed analysis of HSP82 revealed that both Rpd3(L) and Rpd3(S)
      complexes (signified by Sap30 and Rco1, respectively) were recruited to the gene
      promoter, yet only Rpd3(S) was recruited to its open reading frame. A consensus
      URS1 cis-element facilitated the recruitment of each Rpd3 complex to the HSP82
      promoter, and this correlated with targeted deacetylation of promoter
      nucleosomes. Collectively, our observations reveal that SAGA and Rpd3 complexes
      are rapidly and synchronously recruited to heat shock factor 1-activated genes
      and suggest that their opposing activities modulate heat shock gene chromatin
      structure and fine-tune transcriptional output.

PMID- 19759027
TI  - Identification of the GATA factor TRPS1 as a repressor of the osteocalcin
      promoter.
AB  - A proteomic analysis of proteins bound to the osteocalcin OSE2 sequence of the
      mouse osteocalcin promoter identified TRPS1 as a regulator of osteocalcin
      transcription. Mutations in the TRPS1 gene are responsible for human tricho-rhino
      phalangeal syndrome, which is characterized by skeletal and craniofacial
      abnormalities. TRPS1 has been shown to bind regulatory promoter sequences
      containing GATA consensus binding sites and to repress transcription of genes
      involved in chondrocyte differentiation. Here we show that TRPS1 can directly
      bind the osteocalcin promoter in the presence or absence of Runx2. TRPS1 binds
      through a GATA binding sequence in the proximal promoter of the osteocalcin gene.
      The GATA binding site is conserved in mice, humans, and rats, although its
      location and orientation are not. Mutation of the mouse or human GATA binding
      sequence abrogates binding of TRPS1 to the osteocalcin promoter. We show that
      TRPS1 is expressed in osteosarcoma cells and upon induction of osteoblast
      differentiation in primary mouse bone marrow stromal cells and that TRPS1
      regulates the expression of osteocalcin in both cell types. The expression of
      TRPS1 modulates mineralized bone matrix formation in differentiating osteoblast
      cells. These data suggest a role for TRPS1 in osteoblast differentiation, in
      addition to its previously described role in chondrogenesis.

PMID- 19759028
TI  - Diffuse involvement of the heart and great vessels in primary cardiac lymphoma.
AB  - Primary cardiac lymphoma (PCL) is an extremely rare disorder. In this report, a
      57-year-old male with diffuse large B-cell lymphoma involving the heart and great
      vessels is presented. Trans-thoracic echocardiography was the first modality used
      to establish the diagnosis. Fluorine-18-fluorodeoxyglucose positron emission
      tomography/computed tomography (FDG PET/CT) showed diffuse increased metabolic
      activity of the heart walls and hypermetabolic lesions occupying cardiac chambers
      in some areas. The patient underwent systemic chemotherapy, and after 13 days, a
      marked regression of the tumour mass was evident based on echocardiographic
      examination. After completing six R-CHOP chemotherapy treatments, PET imaging was
      planned to control the residual mass, but the patient was intubated due to
      pneumonia that developed after the sixth chemotherapy session and subsequently
      died due to sepsis.

PMID- 19759029
TI  - Factors affecting the validity of ankle-brachial index in the diagnosis of
      peripheral arterial obstructive disease.
AB  - We evaluated 158 legs from 79 consecutive patients who had undergone both ankle
      brachial index (ABI) measurements and angiography for claudication symptoms
      between January 2007 and December 2008. The diagnosis of peripheral arterial
      disease (PAD) in the individual legs was established by angiography. Ankle
      brachial index was considered abnormal if it was <0.9. The sensitivity and
      specificity of ABI was 61% and 87%, respectively. To assess the factors affecting
      the validity of ABI in the diagnosis of PAD, multivariate logistic regression
      analysis was conducted. The odds ratios (ORs) for the false negative result of
      ABI were 4.36 (95% confidence interval [CI] 1.36-13.92) in patients with diabetes
      mellitus (DM), 3.41 (95% CI 1.10-10.48) in patients with distal lesions, 3.02
      (95% CI 1.07-8.49) in elderly patients, and 1.13 (95% CI 0.34-3.42) in patients
      with mild stenosis. Although ABI is the method of choice for the primary
      diagnosis of PAD, other supplementary investigations should be considered when
      there is clinical suspicion of PAD but an ABI <0.9.

PMID- 19759030
TI  - Do men and women respond differently to percutaneous renal artery interventions?
AB  - BACKGROUND: Women have higher risk of contrast-induced nephropathy than men. The
      purpose of this study was to determine the relative impact of gender on long-term
      renal function after percutaneous renal interventions (PRI). METHODS AND RESULTS:
      We included all patients undergoing PRI. Men (n = 72) and women (n = 28) had
      similar age, men had more diabetes, coronary and peripheral artery disease,
      higher serum creatinine and similar glomerular filtration rate (GFR), and
      prevalence of chronic kidney disease (CKD) stage > or =3 when compared with
      females. At follow-up, men had a significant improvement in GFR and systolic
      blood pressure, while females did not. The presence of severe CKD and male gender
      were the only predictors of long-term GFR improvement. CONCLUSION: Male patients
      and patients with poor baseline renal function showed an important benefit with
      PRI, suggesting that it is not too late for renal revascularization if properly
      indicated.

PMID- 19759031
TI  - Oxidative stress and platelet activation: markers of myocardial infarction in
      type 2 diabetes mellitus.
AB  - We compared lipids, lipid peroxidation product malondialdehyde (MDA), the acute
      phase reactant high-sensitivity C-reactive protein (hsCRP), interleukin 1beta (IL
      1beta), and platelet selectin (P-selectin) between healthy controls, type 2
      diabetes mellitus (DM) participants without myocardial infarction (MI), as well
      as type 2 DM participants with MI. Malondialdehyde, IL-1beta, and P-selectin
      levels were significantly higher in the diabetic participants with MI than in
      either healthy controls or diabetic participants without MI. In the diabetic
      groups, fasting blood glucose (FBG) level, glycated hemoglobin (HbA(1c)), MDA,
      hsCRP, and P-selectin were all significantly positively correlated with each
      other. This study suggests that increased levels of oxidative stress markers,
      proinflammatory markers, and adhesion molecules contribute to the atherosclerotic
      process that eventually leads to coronary artery disease in diabetic patients.

PMID- 19759032
TI  - Response to facial massage and bilateral carotid and bilateral vertebral artery
      dissection.

PMID- 19759034
TI  - The bounce of the body in hopping, running and trotting: different machines with
      the same motor.
AB  - The bouncing mechanism of human running is characterized by a shorter duration of
      the brake after 'landing' compared with a longer duration of the push before
      'takeoff'. This landing-takeoff asymmetry has been thought to be a consequence of
      the force-velocity relation of the muscle, resulting in a greater force exerted
      during stretching after landing and a lower force developed during shortening
      before takeoff. However, the asymmetric lever system of the human foot during
      stance may also be the cause. Here, we measure the landing-takeoff asymmetry in
      bouncing steps of running, hopping and trotting animals using diverse lever
      systems. We find that the duration of the push exceeds that of the brake in all
      the animals, indicating that the different lever systems comply with the basic
      property of muscle to resist stretching with a force greater than that developed
      during shortening. In addition, results show both the landing-takeoff asymmetry
      and the mass-specific vertical stiffness to be greater in small animals than in
      large animals. We suggest that the landing-takeoff asymmetry is an index of a
      lack of elasticity, which increases with increasing the role of muscle relative
      to that of tendon within muscle-tendon units.

PMID- 19759035
TI  - Evolution of weaponry in female bovids.
AB  - Weaponry is ubiquitous in male ungulates and is driven by intrasexual selection,
      but the mystery surrounding its sporadic presence in females remains unsolved.
      Female horns are often smaller and shaped differently to male horns, suggesting a
      different function; indeed, hypotheses explaining the presence of female horns
      include competition for food, male mollification and defence against predators.
      Here we use comparative phylogenetic analyses to show that females are
      significantly more likely to bear horns in bovids that are conspicuous due to
      large body size and living in open habitats than inconspicuous species living in
      closed habitats or that are small. An inability to rely on crypsis or take refuge
      in deep vegetation has apparently driven the evolution of horns for defence
      against predators in female bovids, a finding supported by many field
      observations. Typically, exceptions are small species where females are
      territorial (e.g. duikers) and use horns in intrasexual contests. Furthermore, we
      suggest that conspicuousness and territoriality hypotheses may explain other
      instances of female cranial weaponry (i.e. antlers and ossicones) in other horned
      ruminants. Our phylogenetic reconstruction indicates that the primary function of
      horns in females is linked to antipredator defence in most clades, but
      occasionally to intrasexual competition in others.

PMID- 19759036
TI  - Assessing the root of bilaterian animals with scalable phylogenomic methods.
AB  - A clear picture of animal relationships is a prerequisite to understand how the
      morphological and ecological diversity of animals evolved over time. Among
      others, the placement of the acoelomorph flatworms, Acoela and Nemertodermatida,
      has fundamental implications for the origin and evolution of various animal organ
      systems. Their position, however, has been inconsistent in phylogenetic studies
      using one or several genes. Furthermore, Acoela has been among the least stable
      taxa in recent animal phylogenomic analyses, which simultaneously examine many
      genes from many species, while Nemertodermatida has not been sampled in any
      phylogenomic study. New sequence data are presented here from organisms targeted
      for their instability or lack of representation in prior analyses, and are
      analysed in combination with other publicly available data. We also designed new
      automated explicit methods for identifying and selecting common genes across
      different species, and developed highly optimized supercomputing tools to
      reconstruct relationships from gene sequences. The results of the work
      corroborate several recently established findings about animal relationships and
      provide new support for the placement of other groups. These new data and methods
      strongly uphold previous suggestions that Acoelomorpha is sister clade to all
      other bilaterian animals, find diminishing evidence for the placement of the
      enigmatic Xenoturbella within Deuterostomia, and place Cycliophora with
      Entoprocta and Ectoprocta. The work highlights the implications that these
      arrangements have for metazoan evolution and permits a clearer picture of
      ancestral morphologies and life histories in the deep past.

PMID- 19759037
TI  - Social learning about egg-laying substrates in fruitflies.
AB  - Social learning, defined as learning from other individuals, has had dramatic
      effects on some species, including humans, in whom it has generated a rich
      culture. As a first step in examining the evolution of and mechanisms underlying
      social learning in insects, we tested for social learning in fruitflies
      (Drosophila melanogaster). Focal females (observers) that experienced novel food
      together with mated females (models), who had laid eggs on that food,
      subsequently exhibited a stronger preference for laying eggs on that food over
      another novel food compared with focal females that experienced the food alone.
      We observed no social learning, however, when observers experienced food with
      potentially more ambiguous social information provided by the presence of either
      virgin models or aggregation pheromone. This first documentation of social
      learning about egg-laying substrates in fruitflies builds on recent data
      indicating intricate use of social information by fruitflies and opens up
      exciting avenues for research on the evolution and neurogenetics of social
      learning using biology's major model system.

PMID- 19759038
TI  - Shifts in leaf vein density through accelerated vein formation in C4 Flaveria
      (Asteraceae).
AB  - BACKGROUND AND AIMS: Leaf venation in many C(4) species is characterized by high
      vein density, essential in facilitating rapid intercellular diffusion of C(4)
      photosynthetic metabolites between different tissues (mesophyll, bundle sheath).
      Greater vein density has been hypothesized to be an early step in C(4)
      photosynthesis evolution. Development of C(4) vein patterning is thought to occur
      from either accelerated or prolonged procambium formation, relative to ground
      tissue development. METHODS: Cleared and sectioned tissues of phylogenetically
      basal C(3) Flaveria robusta and more derived C(4) Flaveria bidentis were compared
      for vein pattern in mature leaves and vein pattern formation in developing
      leaves. KEY RESULTS: In mature leaves, major vein density did not differ between
      C(3) and C(4) Flaveria species, whereas minor veins were denser in C(4) species
      than in C(3) species. The developmental study showed that both major and minor
      vein patterning in leaves of C(3) and C(4) species were initiated at comparable
      stages (based on leaf length). An additional vein order in the C(4) species was
      observed during initiation of the higher order minor veins compared with the C(3)
      species. In the two species, expansion of bundle sheath and mesophyll cells
      occurred after vein pattern was complete and xylem differentiation was continuous
      in minor veins. In addition, mesophyll cells ceased dividing sooner and enlarged
      less in C(4) species than in C(3) species. CONCLUSIONS: Leaf vein pattern
      characteristic to C(4) Flaveria was achieved primarily through accelerated and
      earlier offset of higher order vein formation, rather than other modifications in
      the timing of vein pattern formation, as compared with C(3) species. Earlier
      cessation of mesophyll cell division and reduced expansion also contributed to
      greater vein density in the C(4) species. The relatively late expansion of bundle
      sheath and mesophyll cells shows that vein patterning precedes ground tissue
      development in C(4) species.

PMID- 19759039
TI  - Early reproductive developmental anatomy in Decaisnea (Lardizabalaceae) and its
      systematic implications.
AB  - BACKGROUND AND AIMS: Decaisnea insignis, known as 'dead man's fingers'
      (Lardizabalaceae), is widely distributed in China and the Himalayan foothill
      countries. This economically important plant, which is the only species in the
      genus, has not been the subject of any embryological studies aside from one
      brief, older paper that lacks micrographs. Data on Decaisnea are also important
      because its systematic position has been unstable since the genus was established
      in 1855. Therefore, the objectives of this study were: (a) to use modern
      microscopy to document early reproductive anatomical development in Decaisnea;
      and (b) to compare qualitatively these early embryological characters with allied
      taxa in a systematic context. METHODS: Decaisnea insignis floral buds and
      inflorescences were regularly collected from Shaanxi Province, China and prepared
      for light microscopy. The embryological characters studied were qualitatively
      compared with those of allied taxa via a thorough examination of the existing
      literature. KEY RESULTS: Early reproductive anatomy in Decaisnea was documented
      and novel revelations made. It was discovered that the pollen is shed when three
      celled (not two-celled, as previously reported), and that endosperm formation is
      nuclear (not cellular or helobial, as previously reported). These two newly
      revealed embryological characters are not found in any other members of
      Lardizabalaceae. Furthermore, neither are persistent antipodal cells, which we
      confirmed to be present in Decaisnea. CONCLUSIONS: Decaisnea and other
      Lardizabalaceae characteristically have tetrasporangiate anthers, a secretory
      tapetum, simultaneous microsporocyte cytokinesis, primarily bitegmic,
      crassinucellate ovules, and a Polygonum type embryo sac. However, in the family,
      persistent antipodals, nuclear endosperm, and pollen shed at the three-celled
      stage are only found in Decaisnea. These embryological data prompted the
      suggestion that Decaisnea needs elevation above the level of genus.

PMID- 19759040
TI  - Cellular pharmacokinetics and intracellular activity of torezolid (TR-700):
      studies with human macrophage (THP-1) and endothelial (HUVEC) cell lines.
AB  - BACKGROUND AND AIMS: Optimal treatment of infections caused by Staphylococcus
      aureus, Listeria monocytogenes and Legionella pneumophila requires antibiotics
      with intracellular activity. Linezolid accumulates poorly within cells. Torezolid
      (TR-700) is a novel methyltetrazolyl oxazolidinone with potentially different
      cellular pharmacokinetic properties. Our aim was to examine the accumulation and
      intracellular activities of torezolid in this context. METHODS: Measurement of
      torezolid cell content and antibacterial activity in comparison with linezolid
      using human macrophages (THP-1) and human endothelial cells [human umbilical vein
      endothelial cells (HUVECs)], applying models allowing for the quantitative
      evaluation of the pharmacodynamics of antibiotics towards intracellular bacteria.
      RESULTS: Torezolid accumulated rapidly in THP-1 macrophages, reaching a stable
      intracellular to extracellular ratio of approximately 10 (compared with
      approximately 1-2 for linezolid) within 15 min. On a weight concentration basis
      (mg/L), torezolid was approximately 5- to 10-fold more potent intracellularly
      (lower concentration needed to achieve a bacteriostatic effect) than linezolid
      against phagocytosed S. aureus, L. monocytogenes and L. pneumophila, with no
      change in maximal efficacy (approximately 1 log(10) reduction of the original,
      post-phagocytosis inoculum). When drugs were compared at equipotent
      concentrations (multiples of the MIC), no difference was seen between linezolid
      and torezolid, but the higher potency of torezolid allowed control of
      intracellular infections caused by linezolid-resistant S. aureus. CONCLUSIONS:
      Torezolid exerts intracellular activity at lower extracellular concentrations
      than linezolid because of its greater potency independent of its greater
      intracellular accumulation. This may confer an advantage to torezolid in vivo if
      the drug can be used at dosages creating serum concentrations similar to those
      achieved with linezolid.

PMID- 19759041
TI  - Comparative antibacterial effects of daptomycin, vancomycin and teicoplanin
      studied in an in vitro pharmacokinetic model of infection.
AB  - OBJECTIVES: To compare the antibacterial effects (ABEs) of the free (f) drugs
      daptomycin, vancomycin and teicoplanin against methicillin-resistant
      Staphylococcus aureus (MRSA) and vancomycin-resistant S. aureus (VRSA), using
      high and low inocula in a pharmacokinetic in vitro model. To determine the
      daptomycin fAUC/MIC ratio for a static effect and 3 log reduction in viable count
      and relate this target to the clinical breakpoint. METHODS: Five clinical MRSA
      isolates held at Southmead Hospital were used (SMH 15841, SMH 40289, SMH 40275,
      SMH 33922 and SMH 33024) together with a VRSA isolate (SMH 19898); inocula of
      10(6) and 10(8) cfu/mL were used. Daptomycin (6 mg/kg once daily), vancomycin (1
      g twice daily) and teicoplanin (400 mg once daily) regimens were simulated. ABEs
      were measured using the 24 h area-under-the-bacterial kill curve (AUBKC) and log
      change in viable count at 24 h (Delta24). For daptomycin, dose escalation was
      used to determine the relationship between ABE and AUC/MIC. RESULTS: Daptomycin
      was bactericidal against the MRSA strains. Daptomycin and vancomycin were active
      against the VRSA strain; teicoplanin had a static effect. The higher inoculum
      reduced the ABEs. Analysis of variance (ANOVA) indicated that daptomycin had a
      superior ABE to teicoplanin and vancomycin. Daptomycin fAUC/MIC was related to
      AUBKC and Delta24; the fAUC/MIC ratios for a static effect and 1 log and 3 log
      drop were 37.2 +/- 16.5, 40.6 +/- 17.8 and 49.8 +/- 19.2, respectively.
      CONCLUSIONS: These data define the fAUC/MIC sizes for daptomycin for
      bacteriostatic and bactericidal ABEs and indicate that a 6 mg/kg dose of
      daptomycin is superior to vancomycin and teicoplanin against MRSA and VRSA
      strains.

PMID- 19759042
TI  - Effects of interactions of antibacterial drugs with each other and with 6
      mercaptopurine on in vitro growth of Mycobacterium avium subspecies
      paratuberculosis.
AB  - OBJECTIVES: Mycobacterium avium subspecies paratuberculosis (MAP) has been
      targeted for treatment with clarithromycin and rifamycin derivatives in numerous
      cases of Crohn's disease (CD). 6-Mercaptopurine and its pro-drug azathioprine are
      widely used as immunomodulators in the treatment of CD and have recently been
      shown to have anti-MAP activity in vitro. The objectives of the study were to
      evaluate the in vitro effects on MAP of (i) 6-mercaptopurine when combined with
      each of eight conventional antibacterial agents with in vitro anti-MAP activity
      and (ii) antibacterial combinations consisting of two drugs (clarithromycin
      combined with amikacin, rifampicin, ciprofloxacin or ethambutol) and three drugs
      (clarithromycin, rifabutin and clofazimine). METHODS: The drug interaction
      effects on nine human isolates of MAP were determined by the chequerboard method
      adapted for the BACTECMGIT960 culture system and by calculation of the fractional
      inhibitory concentration index (FICI) for drug combinations. RESULTS: Synergism
      (FICI < or = 0.5) was observed between 6-mercaptopurine and azithromycin (seven
      isolates), clarithromycin, rifampicin, rifabutin (four isolates each) and
      ethambutol (two isolates). 6-Mercaptopurine was not antagonistic with any of the
      antibacterial agents tested. Among the combinations of two and three
      antibacterials tested, the clarithromycin/rifampicin combination was synergistic
      against four isolates, while all other combinations showed no interaction.
      CONCLUSIONS: This in vitro study suggests that 6-mercaptopurine may be
      synergistic with macrolides and rifamycin derivatives against MAP. The activity
      of clarithromycin against MAP seems to be enhanced by rifampicin.

PMID- 19759043
TI  - Efficacy and safety of a single daily dose of gentamicin in hospitalized Indian
      children: a quasi-randomized trial.
AB  - OBJECTIVES: To compare the clinical efficacy, pharmacokinetic profiles and safety
      of once-daily dosing (ODD) and multiple daily dosing (MDD) of gentamicin in
      hospitalized Indian children. PATIENTS AND METHODS: Four hundred children
      admitted to our hospital were studied prospectively. The patients were randomized
      to ODD or MDD groups alternately. The primary outcomes were: (i) a good clinical
      outcome, as defined; and (ii) occurrence of side effects, if any. Clinical
      efficacy was determined by comparing the proportion of patients with a favourable
      response between the two groups, while pharmacokinetic profile was assessed by
      comparing the peak and trough concentrations of the drug in a subgroup of
      patients. Safety of the two regimens was compared, besides recording any symptoms
      due to side effects of the drug, with the help of serum creatinine and brainstem
      evoked response audiometry (in a subgroup of the patients). RESULTS: We found ODD
      of gentamicin in hospitalized Indian children to be efficacious and safe. A
      favourable clinical response was achieved in 167 of the 188 patients (89%) in the
      ODD group and in 161 of the 212 patients (76%) in the MDD group. Similarly, a
      higher number of patients in the ODD group showed favourable gentamicin peak
      concentrations as compared with the MDD group (100% versus 87%). The MDD group
      showed a higher number of trough concentrations in the undesirable range as
      compared with the ODD group (17% versus 0%). CONCLUSIONS: The study supports
      extended-interval (single daily) dosing in hospitalized Indian children due to
      its efficacy and safety with the added advantage of needing fewer injections.

PMID- 19759044
TI  - Exposure of Escherichia coli and Salmonella enterica serovar Typhimurium to
      triclosan induces a species-specific response, including drug detoxification.
AB  - OBJECTIVES: The use of triclosan within various environments has been linked to
      the development of multiple drug resistance (MDR) through the increased
      expression of efflux pumps such as AcrAB-TolC. In this work, we investigate the
      effect of triclosan exposure in order to ascertain the response of two species to
      the presence of this widely used biocide. METHODS: The transcriptomes of
      Salmonella enterica serovar Typhimurium SL1344 and Escherichia coli K-12 MG1655
      after exposure to the MIC of triclosan (0.12 mg/L) were determined in microarray
      experiments. Phenotypic validation of the transcriptomic data included RT-PCR,
      ability to form a biofilm and motility assays. RESULTS: Despite important
      differences in the triclosan-dependent transcriptomes of the two species,
      increased expression of efflux pump component genes was seen in both. Increased
      expression of soxS was observed in Salmonella Typhimurium, however, within E.
      coli, decreased expression was seen. Expression of fabBAGI in Salmonella
      Typhimurium was decreased, whereas in E. coli expression of fabABFH was
      increased. Increased expression of ompR and genes within this regulon (e.g. ompC,
      csgD and ssrA) was seen in the transcriptome of Salmonella Typhimurium. An
      unexpected response of E. coli was the differential expression of genes within
      operons involved in iron homeostasis; these included fhu, fep and ent.
      CONCLUSIONS: These data indicate that whilst a core response to triclosan
      exposure exists, the differential transcriptome of each species was different.
      This suggests that E. coli K-12 should not be considered the paradigm for the
      Enterobacteriaceae when exploring the effects of antimicrobial agents.

PMID- 19759045
TI  - Off-label use of antibiotics in hospitalized patients: focus on tigecycline.

PMID- 19759046
TI  - Creating community action plans for obesity prevention using the ANGELO (Analysis
      Grid for Elements Linked to Obesity) Framework.
AB  - Community-based interventions are an important component of obesity prevention
      efforts. The literature provides little guidance on priority-setting for obesity
      prevention in communities, especially for socially and culturally diverse
      populations. This paper reports on the process of developing prioritized,
      community-participatory action plans for obesity prevention projects in children
      and adolescents using the ANGELO (Analysis Grid for Elements Linked to Obesity)
      Framework. We combined stakeholder engagement processes, the ANGELO Framework
      (scans for environmental barriers, targeted behaviours, gaps in skills and
      knowledge) and workshops with key stakeholders to create action plans for six
      diverse obesity prevention projects in Australia (n = 3), New Zealand, Fiji and
      Tonga from 2002 to 2005. Some sites included sociocultural contextual analyses in
      the environmental scans. Target groups were under-5-year-olds (Australia), 4-12
      year-olds (Australia) and 13-18-year-olds (all four countries). Over 120
      potential behavioural, knowledge, skill and environmental elements were
      identified for prioritization leading into each 2-day workshop. Many elements
      were common across the diverse cultural communities; however, several unique
      sociocultural elements emerged in some cultural groups which informed their
      action plans. Youth were actively engaged in adolescent projects, allowing their
      needs to be incorporated into the action plans initiating the process of
      ownership. A common structure for the action plan promoted efficiencies in the
      process while allowing for community creativity and innovation. The ANGELO is a
      flexible and efficient way of achieving an agreed plan for obesity prevention
      with diverse communities. It is responsive to community needs, combines local and
      international knowledge and creates stakeholder ownership of the action plan.

PMID- 19759047
TI  - The evolution of an integrated sexual health service.
AB  - The objective of the study was to assess the contributions of different providers
      across an integrated sexual health-care network to the diagnosis of sexually
      transmitted infections (STIs). The method employed was retrospective cross
      sectional survey of laboratory tests for Chlamydia trachomatis, Neisseria
      gonorrhoeae and Trichomonas vaginalis between 01 April 2004 and 31 March 2007.
      The total number of STI screens in all venues rose from 17,126 to 23,679. The
      proportion of STI screens occurring in the genitourinary (GU) medicine clinic
      fell from 75% to 55% (P < 0.0001). There was an 11% increase in male screens
      performed in the community. The number of STIs diagnosed rose from 2354 in 2004
      to 3128 in 2007, with an upward trend of community-diagnosed STIs. In conclusion,
      the role of community services increased during the evolution of the integrated
      sexual health network, although the majority of STIs were diagnosed within in the
      GU medicine clinic. Male screens accounted for one-third of those performed. A
      gap in male attendances remains despite the plurality of services.

PMID- 19759048
TI  - Sexual behaviour, condom use and rates of sexually transmitted infections in HIV
      clinic attendees in South East London.
AB  - The aim of this study was to examine sexual behaviour, condom use and rates of
      sexually transmitted infections (STIs) among attendees at a dedicated on-site STI
      clinic at a South London HIV centre. Data were prospectively collected by using a
      nurse-completed questionnaire. Ninety-eight percent of women reported one or no
      sexual partners in the preceding three months, whereas 57% of men who have sex
      with men (MSM) reported two or more partners. Only 28% of women, 53% of
      heterosexual men and 29% of MSM always used a condom for vaginal or anal
      intercourse. Positive STI diagnoses were found in 17.5% of women, 20% of
      heterosexual men and 49% of MSM. Twenty percent of patients who reported always
      using a condom and 38% of MSM reporting no sexual activity in the preceding three
      months had an STI. These results highlight the need for safe sex promotion and
      STI screening in HIV-infected patients regardless of self-reported sexual
      activity.

PMID- 19759049
TI  - Further observations, mainly serological, on a cohort of women with or without
      pelvic inflammatory disease.
AB  - An analysis was undertaken of data pertaining to over 100 women with lower
      abdominal pain who were laparoscoped. Prior to laparoscopy, 11 of the women were
      considered to almost certainly have salpingitis, of whom six (55%) had
      salpingitis at laparoscopy; 17 to probably have salpingitis, of whom six (35%)
      did; 28 to possibly have salpingitis, of whom five (18%) did; and 56 to be very
      unlikely to have salpingitis, of whom five (9%) did. Of the 22 women who had
      salpingitis at laparoscopy, 14 (64%) had a Chlamydia trachomatis IgG antibody
      titre of >or=1:128 and might reasonably be regarded as having chlamydial disease
      on this basis; six without such a titre probably did not have chlamydial disease
      as C. trachomatis could not be detected at any genital site. At laparoscopy, 18
      women had adhesions without obvious tubal inflammation; clinically, 15 of them
      had been regarded as possibly having salpingitis or unlikely to have it, with 12
      having chronic pelvic pain. Twelve (67%) of the 18 women had a chlamydial IgG
      antibody titre of >or=1:128. IgM antibody was also detected most often in the
      'salpingitis' group. Of 49 women without any abnormality detected at laparoscopy,
      nine (18%) had a high chlamydial IgG antibody titre. Overall, a woman who had a
      high titre of chlamydial IgG antibody and acute pelvic pain, together with a
      clinical picture of pelvic inflammation, was more likely to have salpingitis than
      adhesions alone. Likewise, a woman who had a high titre of chlamydial IgG
      antibody and chronic pelvic pain, together with a clinical picture suggesting
      that salpingitis was unlikely, was more likely to have adhesions alone than acute
      chlamydial salpingitis. However, while antibody measurement and seeking cervical
      C. trachomatis may help in formulating a diagnosis, there seems no simple way of
      detecting the small proportion of women who are infected by C. trachomatis in the
      upper genital tract but whose laparoscopic findings indicate normality. So far as
      patient care is concerned, the only way of preventing damage to the upper genital
      tract is to treat early on the basis of suspicion.

PMID- 19759050
TI  - A comparison of the rates of cisplatin (cDDP)--induced nephrotoxicity associated
      with sodium loading or sodium loading with forced diuresis as a preventative
      measure.
AB  - OBJECTIVE: To determine whether forced diuresis and sodium loading or sodium
      loading alone is better at preventing cisplatin-induced nephrotoxicity. METHODS:
      Records of 92 patients receiving cisplatin >40 mg/m(2) and sodium loading with or
      without mannitol were reviewed to determine the incidence of nephrotoxicity,
      average decline in creatinine clearance, degree of nephrotoxicity, time to
      resolution, rates of hospitalization, and electrolyte abnormalities among
      patients receiving sodium loading or sodium loading with forced diuresis.
      RESULTS: The mean cisplatin dose was 64.5 mg/m(2) with a majority of the subjects
      receiving treatment for lung cancer. The patients who received sodium loading
      experienced an average decline in creatinine clearance of 33.9 mL/min versus a
      decline of 38.9 mL/min in the group receiving forced diuresis and sodium loading
      (p = 0.09). Incidence of nephrotoxicity, rate of hospitalization and rates of
      hypokalemia or hypomagnesemia were similar between the groups. Time to resolution
      of nephrotoxicity was significantly different between the groups, although there
      were limitations in evaluating this outcome. Majority of the subjects in the
      sodium loading group experienced NCIC-TC Grade 0 nephrotoxicity, whereas half of
      the patients in the forced diuresis group experienced Grade 2 nephrotoxicity.
      CONCLUSION: We detected no difference in the prevention of cisplatin-induced
      nephrotoxicity when patients were treated with sodium loading alone or with
      sodium loading with mannitol. No differences were detected in average decrease in
      creatinine clearance, incidence of nephrotoxicity, or rates of hypomagnesemia and
      hypokalemia. The difference in time to resolution of toxicity appeared to be
      significant, however there were limitations in evaluating this outcome.

PMID- 19759051
TI  - Long-term stability of tramadol chlorhydrate and metoclopramide hydrochloride in
      dextrose 5% polyolefin bag at 4 degrees C.
AB  - OBJECTIVES: Preparation of intravenous solution in advance could be efficient to
      improve quality assurance, security, time management, and cost saving of drug
      delivery. The purpose of this study was to investigate the stability of a mixture
      of tramadol chlorhydrate and metoclopramide hydrochloride in dextrose 5%
      polyolefin bags at 4 degrees C. METHODS: The stability of five bags of solution
      containing 100 mg tramadol and 10 mg metoclopramide per 100 mL dextrose 5% and
      stored at 4 degrees C was studied during 32 days and concentrations measured by
      high performance liquid chromatography-diode array detection. RESULTS: No
      degradation interference nor modification in retention times were observed
      throughout the study period. At day 32, tramadol concentration was 96.9% +/- 2.1
      and metoclopramide 97.2% +/- 1.3 of the initial concentration. CONCLUSION: Based
      on a shelf-life of 90% residual potency, tramadol and metoclopramide were
      compatible and stable for at least 32 days at 4 degrees C and can be prepared in
      advance in a centralized intravenous additive service facility.

PMID- 19759052
TI  - Busulfan systemic exposure after oral administration of extemporeanously prepared
      high-dose busulfan capsules.
AB  - PURPOSE: The aim of the study was to analyze patients' busulfan (BU) exposure
      after oral administration of extemporeanously prepared BU capsules prior to blood
      stem cell transplantation. METHODS: Patients were treated with 1 mg/kg body
      weight BU administered orally every 6h on each of 4 consecutive days prior to
      blood stem cell transplantation. Each BU dose was administered in 1 gelatine
      capsule to be swallowed and containing the individually calculated dose of pure
      BU active substance. Blood samples were obtained from 6 adult patients 0, 30, 60,
      90, 120, 180, 240, 300, and 360 min after the 1st, 5th, and 13th BU dose, frozen
      and analyzed subsequently by using a HPLC assay with UV detection. In addition,
      in two patients concomitant TDM was executed. BU exposure was monitored
      concurrently and BU doses were targeted to achieve a steady-state plasma
      concentration (C(SS)) of 600-900 ng/mL or 900-1100 ng/mL depending on the
      underlying disease. In these patients blood samples were obtained 0, 60, 120,
      180, 240, and 360 min after the 1st, 5th, 9th, and 13th BU dose and analyzed
      concurrently. RESULTS: For the six patients monitored retrospectively, the time
      to reach peak plasma BU concentration (C(max)) ranged from 1 to 5 h (mean 2.4 h).
      BU C(max) - values varied from 728 to 1807 ng/ mL (mean 1174 ng/mL), and BU
      clearance (CL/F) from 2.32 to 3.75 mL/min/kg (mean 2.97 mL/min/ kg). The mean BU
      steady state (C(SS)) concentration calculated was 973 ng/mL (range 754-1226
      ng/mL) with a mean AUC of 5818 ng.h/mL (range 4521- 7171 ng.h/mL). One of the two
      patients receiving targeted BU doses required an upward dose adjustment. None of
      the eight patients suffered from vomiting during BU therapy. CONCLUSIONS: BU
      active substance encapsulated without further excipients in gelatine capsules is
      highly suitable for oral BU therapy. However, therapeutic drug monitoring and BU
      dose adjustment is still advisable to achieve optimal systemic BU exposure in
      each individual patient.

PMID- 19759053
TI  - Aprepitant-associated ifosfamide neurotoxicity.

PMID- 19759055
TI  - Optical imaging-guided cancer therapy with fluorescent nanoparticles.
AB  - The diagnosis and treatment of cancer have been greatly improved with the recent
      developments in nanotechnology. One of the promising nanoscale tools for cancer
      diagnosis is fluorescent nanoparticles (NPs), such as organic dye-doped NPs,
      quantum dots and upconversion NPs that enable highly sensitive optical imaging of
      cancer at cellular and animal level. Furthermore, the emerging development of
      novel multi-functional NPs, which can be conjugated with several functional
      molecules simultaneously including targeting moieties, therapeutic agents and
      imaging probes, provides new potentials for clinical therapies and diagnostics
      and undoubtedly will play a critical role in cancer therapy. In this article, we
      review the types and characteristics of fluorescent NPs, in vitro and in vivo
      imaging of cancer using fluorescent NPs and multi-functional NPs for imaging
      guided cancer therapy.

PMID- 19759056
TI  - Neighbourhood socioeconomic status and biological 'wear and tear' in a nationally
      representative sample of US adults.
AB  - OBJECTIVE: To assess whether neighbourhood socioeconomic status (NSES) is
      independently associated with disparities in biological 'wear and tear' measured
      by allostatic load in a nationally representative sample of US adults. DESIGN:
      Cross-sectional study. SETTING: Population-based US survey, the Third National
      Health and Nutrition Examination Survey (NHANES III), merged with US census data
      describing respondents' neighbourhoods. PARTICIPANTS: 13,184 adults from 83
      counties and 1805 census tracts who completed NHANES III interviews and medical
      examinations and whose residential addresses could be reliably geocoded to census
      tracts. MAIN OUTCOME MEASURES: A summary measure of biological risk,
      incorporating nine biomarkers that together represent allostatic load across
      metabolic, cardiovascular and inflammatory subindices. RESULTS: Being male,
      older, having lower income, less education, being Mexican-American and being both
      black and female were all independently associated with a worse allostatic load.
      After adjusting for these characteristics, living in a lower NSES was associated
      with a worse allostatic load (coefficient -0.46; CI -0.079 to -0.012). The
      relationship between NSES and allostatic load did not vary significantly by
      gender or race/ethnicity. CONCLUSIONS: Living in a lower NSES in the USA is
      associated with significantly greater biological wear and tear as measured by the
      allostatic load, and this relationship is independent of individual SES
      characteristics. Our findings show that where one lives is independently
      associated with allostatic load, thereby suggesting that policies that improve
      NSES may also yield health returns.

PMID- 19759057
TI  - Psychosocial and sociodemographic predictors of attrition in a longitudinal study
      of major depression in primary care: the predictD-Spain study.
AB  - BACKGROUND: Few data exist on the psychosocial factors associated with attrition
      in longitudinal surveys. This study was undertaken to determine psychosocial and
      sociodemographic predictors of attrition from a longitudinal study of the onset
      and persistence of episodes of major depression in primary care. METHODS: A
      systematic random sample of general practice attendees was recruited in seven
      Spanish provinces between October 2005 and February 2006. Major depression was
      diagnosed using the Composite International Diagnostic Interview and a set of 39
      individual and environmental risk factors for depression were assessed at
      baseline and after 6 and 12 months of follow-up. Data were analysed using
      multilevel logistic regression. RESULTS: 7777 primary care attendees aged 18-75
      years were selected, of whom 1251 (16.1%) were excluded. Of the remaining 6526,
      1084 (16.6%) refused to participate. Thus, 5442 patients (attending 231 family
      physicians in 41 health centres) were interviewed at baseline, of whom 3804 (70%)
      and 3567 (66%) remained at 6 and 12 months of follow-up, respectively. The
      province and sociodemographic factors were stronger predictors of attrition than
      psychosocial factors. Depression and anxiety had no effect but other psychosocial
      factors affected attrition. There were different profiles for the patients lost
      at 12 months when predictors measured at baseline versus 6 months were included.
      CONCLUSIONS: These findings suggest that several psychosocial factors might be
      considered factors of attrition in primary care cohorts and confirm that baseline
      characteristics are insufficient for analysing non-response in longitudinal
      studies, indicating that different retention strategies should be applied for
      patients interviewed at 6 and 12 months.

PMID- 19759058
TI  - Proteome-wide substrate analysis indicates substrate exclusion as a mechanism to
      generate caspase-7 versus caspase-3 specificity.
AB  - Caspase-3 and -7 are considered functionally redundant proteases with similar
      proteolytic specificities. We performed a proteome-wide screen on a mouse
      macrophage lysate using the N-terminal combined fractional diagonal
      chromatography technology and identified 46 shared, three caspase-3-specific, and
      six caspase-7-specific cleavage sites. Further analysis of these cleavage sites
      and substitution mutation experiments revealed that for certain cleavage sites a
      lysine at the P5 position contributes to the discrimination between caspase-7 and
      -3 specificity. One of the caspase-7-specific substrates, the 40 S ribosomal
      protein S18, was studied in detail. The RPS18-derived P6-P5' undecapeptide
      retained complete specificity for caspase-7. The corresponding P6-P1 hexapeptide
      still displayed caspase-7 preference but lost strict specificity, suggesting that
      P' residues are additionally required for caspase-7-specific cleavage. Analysis
      of truncated peptide mutants revealed that in the case of RPS18 the P4-P1
      residues constitute the core cleavage site but that P6, P5, P2', and P3' residues
      critically contribute to caspase-7 specificity. Interestingly, specific cleavage
      by caspase-7 relies on excluding recognition by caspase-3 and not on increasing
      binding for caspase-7.

PMID- 19759059
TI  - The mtDNA nt7778 G/T polymorphism affects autoimmune diseases and reproductive
      performance in the mouse.
AB  - Mitochondria are organelles of all nucleated cells, and variations in mtDNA
      sequence affect a wide spectrum of human diseases. However, animal models for
      mtDNA-associated diseases are rare, making it challenging to explore mechanisms
      underlying the contribution of mitochondria. Here, we identify a polymorphism in
      the mitochondrial genome, G-to-T at position 7778, which results in an aspartic
      acid-to-tyrosine (D-Y) substitution in the fifth amino acid of the highly
      conserved N-terminus of ATP synthase 8 (ATP8). Using a series of conplastic
      strains we show that this polymorphism increases susceptibility to multiple
      autoimmune diseases, including collagen-induced arthritis, autoimmune diabetes,
      nephritis and autoimmune pancreatitis. In addition, it impairs reproductive
      performance in females, but only in the MRL/MpJ strain. We also demonstrate that
      the mtAtp8 polymorphism alters mitochondrial performance, increasing H(2)O(2)
      production and affecting mitochondrial structure. Functional analysis reveals
      that the polymorphism increase the CD4 T cell adaptive potential to an oxidative
      phosphorylation impaired condition. Our findings provide direct experimental
      evidence for the role of mitochondria in autoimmunity and reproduction.

PMID- 19759060
TI  - Regional cerebral perfusion for surgical correction of neonatal aortic arch
      obstruction.
AB  - One-stage repair of aortic arch obstruction and associated cardiac anomalies is a
      surgical challenge in infants.The purpose of the present study is to review the
      current outcome using regional cerebral perfusion (RCP) during a procedure
      correcting interrupted aortic arch (IAA) and also isolated aortic coarctation
      (CoA) and CoA combined with hypoplastic aortic arch (CoA-HyAA) in our center.
      Between January 2007 and July 2008, 24 infant patients with interrupted aortic
      arch (IAA) (n=3), isolated aortic coarctation (iCoA) (n=9) and aortic coarctation
      with hypoplastic aortic arch (CoA-HyAA) (n=12) underwent one-stage surgical
      correction in our hospital. End-to-end anastomosis was employed in 12 infants
      (IAA n=3 and iCoA n=9); for the other 12 patients with CoA-HyAA, an end-to-end
      extended anastomosis was used in 8 cases, end-to-side anastomosis in 2 cases, and
      composite heterologous pericardial patch in 2 cases. RCP with 40 mL/kg/min
      through the innominate artery during aortic arch reconstruction was employed for
      all pediatric patients. One single-dose histidine-ketoglutarate-tryptophan (HTK)
      solution was used for myocardial protection during CPB. Cardiopulmonary bypass
      time and aortic cross-clamp time were 165.6+/-32.4 min and 81.7+/-30.0 min,
      respectively. The mean regional cerebral perfusion time was 31.0+/-10.6 min;
      lowest nasopharyngeal temperature was 19.1+/-1.1 degrees C. Operative mortality
      rate in both groups was 8.3%. Mean follow-up was 10.5+/-4.8 months. There was no
      late mortality or postoperative neurologic, renal or hepatic complications. All
      patients are asymptomatic and are developing normally. One-stage total arch
      repair using the RCP technique is an excellent method that may minimize
      neurologic and renal complications. Our surgical strategy for arch anomaly has a
      low rate of residual and recurrent coarctation when performed in these infants.

PMID- 19759061
TI  - Adapter proteins and promoter regulation of the angiotensin AT2 receptor-
      implications for cardiac pathophysiology.
AB  - The angiotensin AT( 2) receptor (AT(2)R) represents an important component of the
      renin-angiotensin system since it is involved in the (patho) physiology of
      different cardiovascular and neuronal diseases. Furthermore, AT(2) receptors can
      partly mediate beneficial effects of angiotensin AT( 1) receptor (AT(1)R)
      blockers, and direct pharmacological AT( 2) receptor agonism emerges as a novel
      therapeutic strategy. This review discusses the constitutive and ligand-mediated
      activity as well as the signal transduction of the AT(2) receptor, focusing on
      adapter proteins which directly bind to this receptor. Direct protein-protein
      interaction partners of the AT(2) receptor described so far include the
      transcription factor promyelocytic zinc finger protein, AT(2) receptor binding
      protein and the AT(1) receptor. In addition, the putative crosstalk of the AT(2)
      receptor with the renin/ prorenin receptor (RER) via the promyelocytic zinc
      finger protein (PLZF) and the role of oestrogens on the regulation of the AT(2)
      receptor are presented. Conceiving the coupling of the AT(2) receptor to
      different adapter proteins with distinct and partly opposing cellular effects and
      the implications of its constitutive activity might help to overcome the current
      controversies on the (patho)physiological role of the AT(2) receptor.

PMID- 19759062
TI  - Emotional and behavioural adjustment in siblings of children with intellectual
      disability with and without autism.
AB  - Siblings of children with autism may be at greater risk for psychological
      problems than siblings of children with another disability or of typically
      developing (TD) children. However, it is difficult to establish whether autism or
      the presence of intellectual disability (ID) explains the findings in previous
      research. Mothers rated the emotional and behavioural adjustment of siblings of
      children with ID with (N = 25) or without (N = 24) autism. Data were also
      available 18 months later for siblings of children with autism and ID (N = 15).
      Siblings of children with autism and ID had more emotional problems compared with
      siblings of children with ID only and with normative data. Three variables were
      pertinent: increasing age of the child with autism, having a brother with autism,
      and being younger than the child with autism. Behavioural and emotional
      difficulties of siblings of children with autism and ID were relatively stable
      over 18 months.

PMID- 19759063
TI  - Which DSM-IV-TR criteria best differentiate high-functioning autism spectrum
      disorder from ADHD and anxiety disorders in older children?
AB  - Diagnosis of autism spectrum disorder (ASD) is often delayed in high-functioning
      children with milder and more varied forms of ASD. The substantial overlap
      between ASD and other psychiatric disorders is thought to contribute to this
      delay. This study examined the endorsement of DSM-IV-TR diagnostic criteria for
      ASD based on semi-structured parent interviews across three groups of older
      children referred to an ASD clinic: 55 children diagnosed with high-functioning
      ASD, 27 children diagnosed with attention-deficit/hyperactivity disorder (ADHD),
      and 23 children diagnosed with anxiety disorder. Results indicate that the
      criteria within the domains of communication and social relatedness were largely
      able to discriminate the high-functioning ASD group from the ADHD and anxiety
      disorder groups, but criteria within the domain of
      restricted/repetitive/stereotyped patterns were not.

PMID- 19759064
TI  - Autistic features in girls from a psychiatric sample are strongly associated with
      a low 2D:4D ratio.
AB  - Autistic features such as deficits in social interactions and communication have
      been associated with a low 2D:4D ratio in normal children.This study assessed
      this association in a large sample of children with a variety of psychiatric
      disorders (n = 35 girls and n = 147 boys). Autistic features were assessed with a
      highly valid and reliable measure (Autism Diagnostic Observation Schedule
      Generic). Correlations between the 2D:4D ratio and autistic features were
      computed separately for boys and girls. Some small negative correlations (r = 
      0.17 and r = -0.19) were found in the right hand for boys; however, particularly
      in girls, large negative correlations (r = -0.51 to r = -0.64) were found in the
      left hand. A low 2D:4D ratio in girls was highly predictive of the presence of
      autistic features. Thus, a low ratio could possibly be used as a diagnostic
      predictor in clinical practice.

PMID- 19759065
TI  - Set-shifting in children with autism spectrum disorders: reversal shifting
      deficits on the Intradimensional/Extradimensional Shift Test correlate with
      repetitive behaviors.
AB  - Research examining set-shifting has revealed significant difficulties for adults
      with autism spectrum disorders (ASDs). However, research with high-functioning
      children with ASDs has yielded mixed results. The current study tested 6- to 13
      year-old high-functioning children with ASD and typically developing controls
      matched on age, gender, and IQ using the Intradimensional/Extradimensional
      (ID/ED) Shift Test from the Cambridge Neuropsychological Test Automated Battery.
      Children with ASDs completed as many ED shifts and reversal ED shifts as
      controls; however, they made significantly more errors than controls while
      completing the ED reversal shifts. Analyses on a subset of cases revealed a
      significant positive correlation between ED reversal errors and the number of
      repetitive behavior symptoms in the ASD group. These findings suggest that high
      functioning children with ASDs require additional feedback to shift successfully.
      In addition, the relationship between set-shifting and non-social symptoms
      suggests its utility as a potentially informative intermediate phenotype in ASDs.

PMID- 19759066
TI  - Editorial: organizational matters.

PMID- 19759067
TI  - Enough's enough: conversations with myself and other practitioners.
AB  - Amidst considerable media focus on the stresses and strains on health services
      personnel who choose to leave the service, the author interviewed child mental
      health colleagues about how they coped with organizational stress in the UK
      National Health Service (NHS). The themes that emerged suggest that clinical
      staff feel senior managers have lost touch with what is described as the primary
      task - that of caring for the children and families that use the service.
      Practitioners feel undervalued and overwhelmed by nonclinical activities.
      Although stressed, the kinds of coping mechanisms described are likely to
      maintain high levels of stress, rather than reduce them. It is suggested that the
      cognitive dissonance paradigm explains both the stressful nature of practitioner
      experience and the tendency for clinical staff to work even harder in
      circumstances of perceived oppression. Perceptual Control and general systemic
      theories may help provide a framework in which to understand the dynamic forces
      at work that maintain the clinical and senior management groups in a state of
      perpetual conflict.

PMID- 19759068
TI  - Working appreciatively to improve services for children and families.
AB  - Service improvement approaches are described that specifically focus on
      appreciating the positive that individuals bring to contexts related to children
      and family services. This includes application of Solution-Focused approaches,
      Appreciative Inquiry and other approaches that promote a positive emotional
      climate and focus on what works. Their conceptual foundations are explored and
      particularly their value in supporting working well with complex adaptive
      systems. Specific applications described include leadership and management
      practice, work in school settings, engaging clinicians in healthcare improvement,
      establishing clinical networks, work with homeless youth, child protection and
      approaches to drawing out best practice and community development. The theme that
      unites is a focus on developing effective relationships at all levels and a
      pragmatic focus on what works so that we can find opportunities to do more of it.

PMID- 19759069
TI  - Do unconscious processes affect educational institutions?
AB  - In this article I discuss the way that aspects of school and teaching have
      unconscious roots. Where anxiety about the process, for teachers and children, is
      high then there is the risk that unconscious defensive processes may occur
      resulting in institutionalized phenomena. These take the form of cultural
      attitudes and common practices which may not necessarily enhance the work and in
      some cases may actively interfere.

PMID- 19759070
TI  - Test of time: a case study in the functioning of social systems as a defence
      against anxiety: rereading 50 years on.
AB  - In this paper I revisit Isabel Menzies's classic 'nursing paper' (I.E.P. Menzies
      [1960]. A case-study in the functioning of social systems as a defence against
      anxiety: A report on a study of the nursing service of a general hospital. Human
      Relations, 13, 95-121). I outline the main findings of the paper and connect it
      to the major theoretical developments made by the Tavistock Institute of Human
      Relations and consider the current relevance of the paper in the contemporary
      field of health and social care.

PMID- 19759071
TI  - Soapbox: interprofessional working: choice or destiny?
AB  - This article suggests that there may be profound obstacles to our capacity to
      work together effectively across professional or disciplinary boundaries. These
      problems are rooted in our love of ourselves and our professions and our dislike
      of those not like us, dynamics which are also central to the production of our
      positive professional identities. Such a thickly textured notion of professional
      identity is at odds with contemporary health and welfare policy trends which
      stress 'role performance' as the start and finish of professional activity. Such
      shallow concepts of identity are an affront to the real ethical difficulties
      facing us as we struggle to move beyond professional narcissism and engage with
      the different professional 'other'.

PMID- 19759072
TI  - Visiting the native land.

PMID- 19759073
TI  - A controlled clinical evaluation of the parents plus children's programme: a
      video-based programme for parents of children aged 6 to 11 with behavioural and
      developmental problems.
AB  - This article describes the development and the clinic-based evaluation of the
      Parents Plus Children's Programme (PPCP), a group-based video-modelling-assisted
      programme for parents of children aged 6 to 11 referred to a Child Mental Health
      Service with significant behavioural problems both with and without associated
      developmental difficulties. In evaluating the programme, a sequential block
      design was used to assign 74 parents of children referred to the service to the
      PPCP group (n = 42) or the Treatment as Usual (TAU) Comparison Group (n = 32).
      Assessment took place before and immediately following the 8-week intervention
      for both groups and at 5-month follow-up for the PPCP Group. Compared to the TAU
      Group postprogramme, the PPCP Group displayed significant reductions in total
      difficulties and conduct problems as measured by the Strengths and Difficulties
      Questionnaire, decreased parental stress, increased parental confidence and
      significant improvements in parent-defined problems and goals. These positive
      changes were maintained at 5-month follow-up for the PPCP group, in addition to
      further significant improvements in peer problems and prosocial behaviour. The
      analysis also suggests that the programme is more effective for parents of
      children with behavioural problems only, than for those with associated
      developmental difficulties. The strengths and limitations of the study are
      discussed, as well as the difficulties of conducting practice-based research.

PMID- 19759074
TI  - Attachment research and eating disorders: a review of the literature.
AB  - The aim of this article is to review the clinical literature which examines the
      association between attachment patterns and eating disorders with a focus on
      anorexia nervosa, and to examine the varieties of methods and measures employed
      in attachment research. A literature review was carried out and the relevant
      articles are examined in terms of their contribution to this area. The literature
      indicates a number of important considerations when working with this group,
      including extreme separation anxiety and unresolved loss and trauma, and
      discusses the implications of these findings for treatment. The results also
      indicate conflicting evidence regarding associations between attachment style and
      eating disorder subgroup suggesting that severity of disorder matters more than
      eating disorder subtype. The different ways of investigating attachment patterns
      and experiences are explored in this paper. It is suggested that the attachment
      classification system runs the risk of reducing complex human experience to
      typologies and that qualitative research might help to address this problem.

PMID- 19759075
TI  - Medically unexplained physical symptoms in children: exploring hospital staff
      perceptions.
AB  - Many children present at GP surgeries with debilitating symptoms with no obvious
      physical cause and are then referred to acute settings for investigation.
      Research with GPs suggests caring for this group of patients presents a
      significant challenge, however, the impact upon the range of hospital staff with
      whom they have contact has been little studied. This study aimed to explore
      perceptions and experiences of caring for children with medically unexplained
      physical symptoms (MUPS) and their families among the paediatric staff at one
      large UK hospital Trust. Data demonstrated staff awareness that children affected
      by MUPS have complex needs and the perception that those needs resulted in extra
      demands and anxieties, especially regarding time management, care protocols and
      communication. There was a clear desire by general paediatric staff for more
      information and training from psychiatric services to help them care for this
      group. Results also revealed staff perceptions of the quality of current MUPS
      care and suggestions as to how this could be improved.

PMID- 19759076
TI  - Understanding and knowledge of psychiatric treatment among adolescents and
      adults.
AB  - We evaluated the level of adolescent psychiatric patients' knowledge and
      understanding of their treatment in light of their competency to participate in
      decision-making processes related to their receiving treatment, and compared the
      adolescents' levels of understanding and knowledge to those of adult psychiatric
      patients. The study group consisted of 30 adolescents and 30 adults who were
      randomly selected from the inpatients of our mental health center. Consenting
      participants were interviewed and their objective knowledge of psychiatric
      treatments was evaluated by a specially designed questionnaire. Adolescents knew
      significantly more about adverse effects of treatment and showed a higher level
      of comprehensive general knowledge. These data indicate that adolescents are no
      less knowledgeable than adults and should be regarded as competent partners in
      the process of therapeutic decision making.

PMID- 19759077
TI  - A qualitative exploration of children's understanding of indiscriminate
      friendliness.
AB  - Eight young people (aged 9-14) were interviewed about indiscriminately friendly
      behaviour. The majority of the sample had a history of maltreatment and
      placements within foster and care settings. These young people were described as
      indiscriminately friendly by clinicians, guardians and via the Relationships
      Problems Questionnaire. Interview transcripts were analysed using Interpretative
      Phenomenological Analysis, a qualitative methodology. Emergent themes were drawn
      from interview data which highlighted the young people's experiences of rejection
      and feelings of insecurity within their social interactions. While being aware of
      the risks associated with speaking to strangers and the efforts of adults
      attempting to protect them from the potential danger associated with
      indiscriminate friendliness, this group of young people demonstrated a trust of
      new people and a craving for kindness from others. Evidence was also collected
      which showed that these children attempted to exert control over others during
      social contact. These findings offer clinicians an insight into the social
      interactions of this vulnerable group of children and offer considerations for
      clinical practice.

PMID- 19759078
TI  - Letter to the editors on the nature and balance of articles.

PMID- 19759079
TI  - Metformin associated lactic acidosis.

PMID- 19759080
TI  - Climate Change. Population: the forgotten priority.

PMID- 19759084
TI  - Swine flu vaccine is a "thousandfold" safer than the infection, say experts.

PMID- 19759087
TI  - A review of radiology staff doses and dose monitoring requirements.
AB  - Studies of radiation doses received during X-ray procedures by radiology,
      cardiology and other clinical staff have been reviewed. Data for effective dose
      (E), and doses to the eyes, thyroid, hands and legs have been analysed. These
      data have been supplemented with local measurements to determine the most exposed
      part of the hand for monitoring purposes. There are ranges of 60-100 in doses to
      individual tissues reported in the literature for similar procedures at different
      centres. While ranges in the doses per unit dose-area product (DAP) are between
      10 and 25, large variations in dose result from differences in the sensitivity of
      the X-ray equipment, the type of procedure and the operator technique, but
      protection factors are important in maintaining dose levels as low as possible.
      The influence of shielding devices is significant for determining the dose to the
      eyes and thyroid, and the position of the operator, which depends on the
      procedure, is the most significant factor determining doses to the hands. A
      second body dosemeter worn at the level of the collar is recommended for
      operators with high workloads for use in assessment of effective dose and the
      dose to the eye. It is proposed that the third quartile values from the
      distributions of dose per unit DAP identified in the review might be employed in
      predicting the orders of magnitude of doses to the eye, thyroid and hands, based
      on interventional operator workloads. Such dose estimates could be employed in
      risk assessments when reviewing protection and monitoring requirements. A
      dosemeter worn on the little finger of the hand nearest to the X-ray tube is
      recommended for monitoring the hand.

PMID- 19759088
TI  - Persistent diarrhoea in a young woman.

PMID- 19759090
TI  - An itchy ear that became painful.

PMID- 19759092
TI  - Psychiatric genocide: Nazi attempts to eradicate schizophrenia.
AB  - Although the Nazi genocide of Jews during World War II is well known, the
      concurrent Nazi genocide of psychiatric patients is much less widely known. An
      attempt was made to estimate the number of individuals with schizophrenia who
      were sterilized and murdered by the Nazis and to assess the effect on the
      subsequent prevalence and incidence of this disease. It is estimated that between
      220,000 and 269,500 individuals with schizophrenia were sterilized or killed.
      This total represents between 73% and 100% of all individuals with schizophrenia
      living in Germany between 1939 and 1945. Postwar studies of the prevalence of
      schizophrenia in Germany reported low rates, as expected. However, postwar rates
      of the incidence of schizophrenia in Germany were unexpectedly high. The Nazi
      genocide of psychiatric patients was the greatest criminal act in the history of
      psychiatry. It was also based on what are now known to be erroneous genetic
      theories and had no apparent long-term effect on the subsequent incidence of
      schizophrenia.

PMID- 19759094
TI  - Dioxin-dependent and dioxin-independent gene batteries: comparison of liver and
      kidney in AHR-null mice.
AB  - The aryl hydrocarbon receptor (AHR) is a widely expressed ligand-dependent
      transcription factor that mediates cellular responses to dioxins and other planar
      aromatic hydrocarbons. Ahr-null mice are refractory to the toxic effects of
      dioxin exposure. Although some mechanistic aspects of AHR activity are well
      understood, the tissue specificity of AHR effects remains unclear, both during
      development and following administration of exogenous ligands. To address the
      latter issue, we defined and compared transcriptional responses to dioxin
      exposure in the liver and kidney of wild-type and Ahr-null adult C57BL/6J mice
      treated with either 2,3,7,8-tetrachlorodibenzo-p-dioxin or corn-oil vehicle. In
      both tissues, essentially all effects of dioxin on hepatic mRNA levels were
      mediated by the AHR. Although 297 genes were altered by dioxin exposure in the
      liver, only 17 were changed in the kidney, including a number of well-established
      AHR target genes. Ahr genotype had a large effect in both tissues, profoundly
      remodeling both the renal and hepatic transcriptomes. Surprisingly, a large
      number of genes were affected by Ahr genotype in both tissues, suggesting the
      presence of a basal AHR gene battery. Alterations of the renal transcriptome in
      Ahr-null animals were associated with perturbation of specific functional
      pathways and enrichment of specific DNA motifs. Our results demonstrate the
      importance of intertissue comparisons, highlight the basal role of the AHR in
      liver and kidney, and support a role in development or normal physiology.

PMID- 19759093
TI  - Gray matter in first-episode schizophrenia before and after antipsychotic drug
      treatment. Anatomical likelihood estimation meta-analyses with sample size
      weighting.
AB  - BACKGROUND: Cerebral morphological abnormalities in schizophrenia may be
      modulated by treatment, chronicity, and duration of illness. Comparing brain
      imaging studies of individuals with first-episode schizophrenia and neuroleptic
      naive (NN-FES) with that of their neuroleptic-treated counterparts (NT-FES) can
      help to dissect out the effect of these potential confounders. METHODS: We used
      the anatomical likelihood estimation method to compare voxel-based morphometric
      studies of NN-FES (n = 162 patients) and NT-FES (n = 336 patients) studies. The
      analysis included a sample size weighting step based on the Liptak-Stouffer
      method to reflect the greater power of larger studies. RESULTS: Patient samples
      were matched for age, gender, and duration of illness. An extensive network of
      gray matter deficits in frontal, temporal, insular, striatal, posterior
      cingulate, and cerebellar regions was detected in the NN-FES samples as compared
      with healthy controls. Major deficits were detected in the frontal, superior
      temporal, insular, and parahippocampal regions for the NT-FES group compared with
      the NN-FES group. In addition, the NT-FES group showed minor deficits in the
      caudate, cingulate, and inferior temporal regions compared with the NN-FES group.
      There were no regions with gray matter volumetric excess in the NT-FES group.
      CONCLUSION: Frontal, striato-limbic, and temporal morphological abnormalities are
      present in the early stage of schizophrenia and are unrelated to the effects of
      neuroleptic treatment, chronicity, and duration of illness. There may be dynamic
      effects of treatment on striato-limbic and temporal, but not frontal, regional
      gray matter volumes of the brain.

PMID- 19759095
TI  - Chronic sterile empyema.

PMID- 19759096
TI  - Functional diversity in gravitropic reaction among tropical seedlings in relation
      to ecological and developmental traits.
AB  - Gravitropism is necessary for plants to control the orientation of their axes
      while they grow in height. In woody plants, stem re-orientations are costly
      because they are achieved through diameter growth. The functional diversity of
      gravitropism was studied to check if the mechanisms involved and their efficiency
      may contribute to the differentiation of height growth strategies between forest
      tree species at the seedling stage. Seedlings of eight tropical species were
      grown tilted in a greenhouse, and their up-righting movement and diameter growth
      were measured over three months. Morphological, anatomical, and biomechanical
      traits were measured at the end of the survey. Curvature analysis was used to
      analyse the up-righting response along the stems. Variations in stem curvature
      depend on diameter growth, size effects, the increase in self-weight, and the
      efficiency of the gravitropic reaction. A biomechanical model was used to
      separate these contributions. Results showed that (i) gravitropic movements were
      based on a common mechanism associated to similar dynamic patterns, (ii) clear
      differences in efficiency (defined as the change in curvature achieved during an
      elementary diameter increment for a given stem diameter) existed between species,
      (iii) the equilibrium angle of the stem and the anatomical characters associated
      with the efficiency of the reaction also differed between species, and (iv) the
      differences in gravitropic reaction were related to the light requirements:
      heliophilic species, compared to more shade-tolerant species, had a larger
      efficiency and an equilibrium angle closer to vertical. This suggests that traits
      determining the gravitropic reaction are related to the strategy of light
      interception and may contribute to the differentiation of ecological strategies
      promoting the maintenance of biodiversity in tropical rainforests.

PMID- 19759097
TI  - Is it good noise? The role of developmental instability in the shaping of a root
      system.
AB  - Root architecture plays a major part in determining a root system's ability to
      function effectively and efficiently in its essential roles of anchorage and the
      capture of soil resources. The characteristics of root development that are
      conventionally considered to be the main determinants of root architecture are
      the rate, angle, and duration of root growth and the pattern of root branching.
      In this review, the case is made that there is an additional trait that has been
      largely ignored but which has a significant influence on root architecture,
      namely the degree to which stochasticity (or 'developmental instability') affects
      the developmental process. Although the intrinsic variability in the development
      and growth of lateral roots has been recognized for some time, in almost every
      study of root development this remarkable facet of root behaviour tends to be
      hidden beneath the veil of statistical averaging. Progress in other fields is
      providing intriguing insights into the phenomenon of developmental instability,
      how it is generated at the molecular and cellular levels and the genetic
      mechanisms by which it is buffered. This review will consider the existence of
      developmental instability in roots, its underlying causes, its effects on root
      architecture, and the evidence that it is under genetic control. The hypothesis
      will be advanced that developmental instability in roots is an adaptive trait,
      and its potential relevance to root function will be discussed in both an
      ecological and an agronomic context.

PMID- 19759098
TI  - Exposure to indoor biomass fuel and tobacco smoke and risk of adverse
      reproductive outcomes, mortality, respiratory morbidity and growth among newborn
      infants in south India.
AB  - BACKGROUND: Exposure to indoor air pollution due to open burning of biomass fuel
      is common in low- and middle-income countries. Previous studies linked this
      exposure to an increased risk of respiratory illness, low birth weight (LBW) and
      other disorders. We assessed the association between exposure to biomass fuel
      sources and second-hand tobacco smoke (SHTS) in the home and adverse health
      outcomes in early infancy in a population in rural south India. METHODS: A
      population-based cohort of newborns was followed from birth through 6 months.
      Household characteristics were assessed during an enrolment interview including
      the primary type of cooking fuel and smoking behaviour of household residents.
      Follow-up visits for morbidity were carried out every 2 weeks after delivery.
      Infants were discharged at 6 months when anthropometric measurements were
      collected. RESULTS: 11 728 live-born infants were enrolled and followed, of whom
      92.3% resided in households that used wood and/or dung as a primary source of
      fuel. Exposure to biomass fuel was associated with an adjusted 49% increased risk
      of LBW, a 34% increased incidence of respiratory illness and a 21% increased risk
      of 6-month infant mortality. Exposed infants also had 45 and 30% increased risks
      of underweight and stunting at 6 months. SHTS exposure was also associated with
      these adverse health outcomes except for attained growth. CONCLUSIONS: Open
      burning of biomass fuel in the home is associated with significant health risks
      to the newborn child and young infant. Community-based trials are needed to
      clarify causal connections and identify effective approaches to reduce this
      burden of illnesses.

PMID- 19759099
TI  - 18F-FDG PET/CT for image-guided and intensity-modulated radiotherapy.
AB  - Advances in technology have allowed extremely precise control of radiation dose
      delivery and localization within a patient. The ability to confidently delineate
      target tumor boundaries, however, has lagged behind. (18)F-FDG PET/CT, with its
      ability to distinguish metabolically active disease from normal tissue, may
      provide a partial solution to this problem. Here we review the current
      applications of (18)F-FDG PET/CT in a variety of disease sites, including non
      small cell lung cancer, head and neck cancer, and pancreatic adenocarcinoma. This
      review focuses on the use of (18)F-FDG PET/CT to aid in planning radiotherapy and
      the associated benefits and challenges. We also briefly consider novel
      radiopharmaceuticals that are beginning to be used in the context of radiotherapy
      planning.

PMID- 19759100
TI  - Radiolabeled humanized anti-CD3 monoclonal antibody visilizumab for imaging human
      T-lymphocytes.
AB  - Visilizumab is an IgG(2) humanized monoclonal antibody (mAb) characterized by non
      FcgammaR binding and specific to the CD3 antigen, expressed on more than 95% of
      circulating resting T-lymphocytes and on activated T-lymphocytes homing in
      inflamed tissues. We hypothesized that the use of a radiolabeled anti-CD3
      antibody might serve as a diagnostic tool for imaging T-cell traffic and
      lymphocytic infiltration of tissues and organs affected by autoimmune diseases.
      Here we describe the results of in vitro and animal experiments with (99m)Tc
      succinimidyl-6-hydrazinonicotinate hydrochloride (SHNH)-visilizumab. METHODS: For
      mAb labeling, we used a 2-step method with a heterobifunctional linker SHNH.
      Several titrations were performed to obtain the best labeling efficiency. In
      vitro quality controls included stability assay, cysteine challenge, sodium
      dodecyl sulfate polyacrylamide gel electrophoresis, binding assay, and
      immunoreactivity assay. In vivo studies by high-resolution images were performed
      at 6 and 24 h after the injection of (99m)Tc-SHNH-visilizumab. These included
      cell-targeting experiments in BALB/c mice xenografted subcutaneously with an
      increasing number of HuT78 cells in the leg and displaced with an excess of cold
      antibody. We also studied irradiated severe combined immunodeficient (SCID) mice
      reconstituted with human peripheral blood mononuclear cells (hPBMCs) and injected
      with (99m)Tc-labeled visilizumab or control mAb. After dynamic imaging for 3 h,
      major organs were removed, counted, and processed for immunohistologic
      examination. RESULTS: Visilizumab was labeled with HYNIC with high labeling
      efficiency (>90%) and high specific activity (SA; 10,360-11,100 MBq/mg), with
      retained biochemical integrity and in vitro binding activity to CD3-positive
      cells. The in vivo targeting experiment showed a proportional increase of
      specific uptake with the number of injected cells, both at 6 and at 24 h, and the
      in vivo competition study demonstrated more than 60% decreased uptake after an
      excess of unlabeled antibody. In SCID mice, hPBMCs in different tissues were
      detected by (99m)Tc-labeled visilizumab and confirmed by histology. CONCLUSION:
      Visilizumab can be efficiently labeled with (99m)Tc with high efficiency and SA
      and could be a valuable tool for the study of human T-lymphocyte trafficking and
      lymphocytic infiltration of tissues and organs.

PMID- 19759102
TI  - The 18F-FDG PET cingulate island sign and comparison to 123I-beta-CIT SPECT for
      diagnosis of dementia with Lewy bodies.
AB  - Neuroimaging is increasingly used to supplement the clinical diagnosis of
      dementia with Lewy bodies (DLB) by showing reduced occipital metabolism and
      perfusion and reduced striatal dopaminergic innervation. We aimed to optimize the
      interpretation of (18)F-FDG PET images for differentiating DLB from Alzheimer
      disease (AD) and to compare the results with dopamine transporter imaging using
      (123)I-beta-carbomethoxy-3ss-(4-iodophenyl)tropane ((123)I-beta-CIT) SPECT.
      METHODS: Fourteen subjects with a clinical diagnosis of DLB and 10 with AD
      underwent both (18)F-FDG PET and (123)I-beta-CIT SPECT. Four DLB and 1 AD
      diagnoses were subsequently confirmed at autopsy. Diagnostic accuracy was
      calculated for visual interpretation by 3 readers of standard 3-plane and
      stereotactic surface projection (18)F-FDG PET images, receiver-operating
      characteristic analysis of regional (18)F-FDG uptake, and a cutoff value for the
      striatal-to-occipital binding ratio of beta-CIT defined by receiver-operating
      characteristic analysis. RESULTS: Visual interpretation of 3-plane (18)F-FDG PET
      images had a sensitivity of 83% and specificity of 93% for DLB, slightly higher
      than the results with the stereotactic surface projection images. Regionally,
      hypometabolism in the lateral occipital cortex had the highest sensitivity (88%),
      but relative preservation of the mid or posterior cingulate gyrus (cingulate
      island sign) had the highest specificity (100%). Region-of-interest analysis
      revealed that occipital hypometabolism and relative preservation of the posterior
      cingulate both had a sensitivity of 77% and specificity of 80%. beta-CIT achieved
      100% accuracy and greater effect size than did (18)F-FDG PET (Cohen d = 4.1 vs.
      1.9). CONCLUSION: Both (18)F-FDG PET and (123)I-beta-CIT SPECT appear useful for
      the diagnosis of DLB, although the latter provides more robust results. The
      cingulate island sign may enhance the specificity of (18)F-FDG PET.

PMID- 19759103
TI  - NEMA NU4-2008 image quality performance report for the microPET focus 120 and for
      various transmission and reconstruction methods.
AB  - This work aimed to evaluate the image quality and accuracy of attenuation and
      scatter corrections provided with the microPET Focus 120 scanner using the
      National Electrical Manufacturers Association NU4-2008 image quality phantom.
      METHODS: Attenuation correction was obtained from transmission measurements using
      either a (68)Ge or a (57)Co point source. Fully corrected emission images were
      reconstructed using Fourier rebinning (FORE) and filtered backprojection (FBP).
      For attenuation data obtained with the (57)Co source, fully corrected emission
      images were also reconstructed using FORE and 2-dimensional (2D) ordered-subset
      expectation maximization (OSEM), 3-dimensional (3D) filtered backprojection
      (3DRP), 3D OSEM, and 3D maximum a posteriori methods. The mean activity, the
      coefficients of variation (COVs) of the uniform slices, the recovery coefficients
      (RCs) for hot rods, and the spillover ratio (SOR) for nonemitting water and air
      compartments were measured. RESULTS: For (57)Co-based attenuation correction, the
      mean activity value differed by less than 3% from the true activity. Measuring
      the attenuation with (68)Ge resulted in lower reconstructed activity and higher
      COV. On the basis of (57)Co measurements, the SORs for air and water nonemitting
      compartments were the closest to zero for attenuation correction. The RC measured
      on emission images corrected for attenuation but not for scatter did not show any
      significant difference linked to the transmission method. However, higher RCs
      were noted for transmission measurement with (68)Ge in coincidence with windowing
      when emission data were corrected for attenuation and scatter. This resulted from
      a lower mean value in the uniform area. 2D and 3DRP reconstruction methods showed
      little effect on the mean activity value, whereas iterative 3D methods gave 7%
      higher values. Higher RCs were found with iterative reconstruction than with FBP
      and 3DRP. However, the SOR seemed to be optimal with FBP. SORs were higher with
      iterative methods and decreased with the number of iterations. CONCLUSION: For
      studies of small rodents with the Focus 120, (57)Co transmission seems to be the
      most suitable method for attenuation correction. FORE and 2D reconstruction
      methods appear to be a good compromise between overall image quality and
      reconstruction time: OSEM provides the largest contrasts, but FBP provides
      superior attenuation and scatter correction.

PMID- 19759104
TI  - Quantitative analysis of myocardial perfusion SPECT anatomically guided by
      coregistered 64-slice coronary CT angiography.
AB  - Sequential testing by coronary CT angiography (CTA) and myocardial perfusion
      SPECT (MPS) obtained on stand-alone scanners may be needed to diagnose coronary
      artery disease in equivocal cases. We have developed an automated technique for
      MPS-CTA registration and demonstrate its utility for improved MPS quantification
      by guiding the coregistered physiologic (MPS) with anatomic CTA information.
      METHODS: Automated registration of MPS left ventricular (LV) surfaces with CTA
      coronary trees was accomplished by iterative minimization of voxel differences
      between presegmented CTA volumes and motion-frozen MPS data. Studies of 35
      sequential patients (26 men; mean age, 67 +/- 12 y) with 64-slice coronary CTA,
      MPS, and available results of the invasive coronary angiography performed within
      3 mo were retrospectively analyzed. Three-dimensional coronary vessels and CTA
      slices were extracted and fused with quantitative MPS results mapped on LV
      surfaces and MPS coronary regions. Automatically coregistered CTA images and
      extracted trees were used to correct the MPS contours and to adjust the standard
      vascular region definitions for MPS quantification. RESULTS: Automated
      coregistration of MPS and coronary CTA had the success rate of 96% as assessed
      visually; the average errors were 4.3 +/- 3.3 mm in translation and 1.5 +/- 2.6
      degrees in rotation on stress and 4.2 +/- 3.1 mm in translation and 1.7 +/- 3.2
      degrees in rotation on rest. MPS vascular region definition was adjusted in 17
      studies, and LV contours were adjusted in 11 studies using coregistered CTA
      images as a guide. CTA-guided myocardial perfusion analysis, compared with
      standard MPS analysis, resulted in improved area under the receiver-operating
      characteristic (ROC) curves for the detection of right coronary artery (RCA) and
      left circumflex artery (LCX) lesions (0.84 +/- 0.08 vs. 0.70 +/- 0.11 for LCX, P
      = 0.03, and 0.92 +/- 0.05 vs. 0.75 +/- 0.09 for RCA, P = 0.02). CONCLUSION:
      Software image coregistration of stand-alone coronary CTA and MPS obtained on
      separate scanners can be performed rapidly and automatically, allowing CTA-guided
      contour and vascular territory adjustment on MPS for improved quantitative MPS
      analysis.

PMID- 19759105
TI  - Repeatability of 18F-FDG PET in a multicenter phase I study of patients with
      advanced gastrointestinal malignancies.
AB  - (18)F-FDG PET is often used to monitor tumor response in multicenter oncology
      clinical trials. This study assessed the repeatability of several
      semiquantitative standardized uptake values (mean SUV [SUV(mean)], maximum SUV
      [SUV(max)], peak SUV [SUV(peak)], and the 3-dimensional isocontour at 70% of the
      maximum pixel value [SUV(70%)]) as measured by repeated baseline (18)F-FDG PET
      studies in a multicenter phase I oncology trial. METHODS: Double-baseline (18)F
      FDG PET studies were acquired for 62 sequentially enrolled patients. Tumor
      metabolic activity was assessed by SUV(mean), SUV(max), SUV(peak), and SUV(70%).
      The effect on SUV repeatability of compliance with recommended image-acquisition
      guidelines and quality assurance (QA) standards was assessed. Summary statistics
      for absolute differences relative to the average of baseline values and
      repeatability analysis were performed for all patients and for a subgroup that
      passed QA, in both a multi- and a single-observer setting. Intrasubject precision
      of baseline measurements was assessed by repeatability coefficients, intrasubject
      coefficients of variation (CV), and confidence intervals on mean baseline
      differences for all SUV parameters. RESULTS: The mean differences between the 2
      SUV baseline measurements were small, varying from -2.1% to 1.9%, and the 95%
      confidence intervals for these mean differences had a maximum half-width of about
      5.6% across the SUV parameters assessed. For SUV(max), the intrasubject CV varied
      from 10.7% to 12.8% for the QA multi- and single-observer datasets and was 16%
      for the full dataset. The 95% repeatability coefficients ranged from -28.4% to
      39.6% for the QA datasets and up to -34.3% to 52.3% for the full dataset.
      CONCLUSION: Repeatability results of double-baseline (18)F-FDG PET scans were
      similar for all SUV parameters assessed, for both the full and the QA datasets,
      in both the multi- and the single-observer settings. Centralized quality
      assurance and analysis of data improved intrasubject CV from 15.9% to 10.7% for
      averaged SUV(max). Thresholds for metabolic response in the multicenter
      multiobserver non-QA settings were -34% and 52% and in the range of -26% to 39%
      with centralized QA. These results support the use of (18)F-FDG PET for tumor
      assessment in multicenter oncology clinical trials.

PMID- 19759106
TI  - Safety of radial arterial catheterization in PET research subjects.

PMID- 19759107
TI  - Imaging tumor phenotype: 1 plus 1 is more than 2.

PMID- 19759108
TI  - 2-18F-Fluoropropionic acid as a PET imaging agent for prostate cancer.
AB  - There is a high interest in developing an (18)F-labeled PET tracer that can aid
      in diagnosis and therapy monitoring of prostate cancer. In the current study, we
      have evaluated the potential of 2-(18)F-fluoropropionic acid ((18)F-FPA) as a PET
      tracer for imaging prostate cancer. METHODS: (18)F-FPA was synthesized starting
      from methyl-2-bromopropionate. Small-animal PET studies were performed on mice
      with CWR22rv1, PC-3, DU-145, and LNCaP prostate xenografts, and comparison of
      imaging characteristics of (18)F-FPA with (18)F-FDG uptake is reported.
      Biodistribution studies with (18)F-FPA were performed on mice with CWR22rv1
      xenografts and compared with (14)C-acetate. RESULTS: (18)F-FPA was synthesized in
      44% overall radiochemical yield (decay-corrected). Small-animal PET studies
      revealed that (18)F-FPA can delineate both androgen-dependent and androgen
      independent prostate xenografts with high tumor-to-background ratios. Comparative
      imaging studies demonstrate the superior performance of (18)F-FPA over (18)F-FDG
      for imaging prostate cancer, with excellent tumor-to-background contrast.
      Biodistribution studies show that tumor uptake of the tracer was 5.52 +/- 0.35,
      5.53 +/- 0.42, 5.74 +/- 0.54, and 5.34 +/- 0.19 percentage injected dose (%ID)
      per gram at 1, 2, 3, and 4 h, respectively, after injection. The %ID/g values for
      (18)F-FPA and (14)C-acetate 1 h after tail vein injection were 7.08 +/- 0.80 and
      0.36 +/- 0.08 in tumor, and the corresponding tumor-to-muscle ratios were 1.94
      and 2.06, respectively. CONCLUSION: The data presented here indicate that (18)F
      FPA accumulates in prostate cancers with high tumor-to-background ratios. (18)F
      FPA has potential for use in the clinical diagnosis of prostate cancer in humans.

PMID- 19759109
TI  - Detection of aggressive primary prostate cancer with 11C-choline PET/CT using
      multimodality fusion techniques.
AB  - The aim of the study was to assess whether (11)C-choline PET/CT could identify
      high-risk primary adenocarcinoma of the prostate. METHODS: (11)C-choline PET/CT
      and transpelvic MRI were performed in 14 patients with untreated localized
      primary adenocarcinoma of the prostate, followed by radical prostatectomy as a
      form of primary monotherapy within 14 d of in vivo imaging. To allow accurate
      coregistration of whole-mount histology with in vivo imaging, additional ex vivo
      MR images of the prostatectomy specimen were obtained. Nonlinear 3-dimensional
      image deformations were used for registrations of PET/CT, MRI, and histology.
      Volumes of interest from tumor and benign tissue were defined on the basis of
      histology and were transferred into coregistered (11)C-choline PET/CT volumes to
      calculate the mean (T((mean))/B) and maximum (T((max))/B) ratio of tumor to
      benign prostate background. On the basis of MIB-1/Ki-67 expression in tumor
      tissues represented on a tissue microarray, we assessed whether (11)C-choline
      uptake correlated with local Gleason score and tumor proliferation. RESULTS:
      Histology confirmed 42 tumor nodules with Gleason scores between 3 + 2 and 4 + 4,
      with volumes ranging from 0.03 to 12.6 cm(3). T((mean))/B (P < 0.01) and
      T((max))/B (P < 0.001) ratios were significantly increased in high-Gleason score
      (>or=4 + 3) lesions versus 3 + 4 and lower disease but failed to distinguish
      between 3 + 4 disease versus 3 + 3 and lower. T((mean))/B and T((max))/B ratios
      were significantly increased in tumors with an MIB-1/Ki-67 labeling index greater
      than or equal to 5% (P < 0.01). CONCLUSION: On the basis of our preliminary data
      using ratios of tumor to benign prostate background, (11)C-choline preferentially
      identified aggressive primary prostate cancer.

PMID- 19759110
TI  - Three-step, "one-pot" radiosynthesis of 6-fluoro-3,4-dihydroxy-L-phenylalanine by
      isotopic exchange.
AB  - The (18)F-labeled aromatic amino acid 6-fluoro-3,4-dihydroxy-L-phenylalanine (6
      (18)F-fluoro-L-DOPA) is widely used as a radiopharmaceutical in neurologic and
      oncologic PET. In this study, a novel approach to the preparation of carrier
      added (CA) 6-(18)F-fluoro-L-DOPA in 3 radiosynthesis steps was developed and
      evaluated; in this approach, direct nucleophilic (18)F fluorination of a
      protected amino acid derivative was used. The method currently used for the
      routine preparation of 6-(18)F-fluoro-L-DOPA by electrophilic labeling is limited
      to the production of small amounts of activity at high costs. Alternative
      syntheses based on the advantage of large-scale production of nucleophilic (18)F
      fluoride, however, either have resulted in insufficient enantiomeric purity or
      are difficult to automate because of the complexity of the necessary multiple
      steps. METHODS: An isotopic exchange reaction on the precursor (2S,5S)-tert-butyl
      5-(4-benzyloxy-2-fluoro-5-formylbenzyl)-2-tert-butyl-3-methyl-4-oxoimidazolidine
      1-carboxylate was used. The formyl group served as the activating group in the
      (18)F-for-(19)F exchange with tetrabutylammonium bicarbonate for anion activation
      in N,N-dimethylformamide. The intermediate was converted to a hydroxy group by
      Baeyer-Villiger oxidation with meta-chloroperbenzoic acid. After final
      deprotection with hydrobromic acid, CA 6-(18)F-fluoro-L-DOPA was isolated by high
      performance liquid chromatography. RESULTS: The precursor was obtained by an 11
      step organic synthesis. The optimized isotopic (18)F exchange proceeded with a
      radiochemical yield of about 50%. The complete preparation and isolation of CA 6
      (18)F-fluoro-L-DOPA thus far are possible with a radiochemical yield of about
      22%, within a synthesis time of 105 min, and at a much higher specific activity
      than with the electrophilic method. The enantiomeric excess of the desired L
      isomer was greater than 96%. CONCLUSION: The pathway to 6-(18)F-fluoro-L-DOPA by
      isotopic exchange not only is more efficient but also is suited to automation as
      a "one-pot" procedure.

PMID- 19759111
TI  - Single 20-second acquisition of deep-inspiration breath-hold PET/CT: clinical
      feasibility for lung cancer.
AB  - This study was designed to compare tumor (18)F-FDG uptake between a single 20-s
      acquisition of deep-inspiration breath-hold PET/CT and free-breathing PET/CT for
      lung cancer. METHODS: Before the clinical study, a phantom study was performed to
      determine the optimum breath-hold time for the PET scan. We studied 47 patients
      with lung cancer who underwent free-breathing PET/CT with the standard clinical
      protocol, followed by deep-inspiration breath-hold PET/CT of the thorax. In
      breath-hold PET/CT, the patients were asked to hold their breath in deep
      inspiration for 10 s during the CT scan and for 20 s during the PET scan. Maximum
      tumor (18)F-FDG standardized uptake value (SUVmax) was measured in free-breathing
      PET and breath-hold PET, and the percentage difference between these 2 values was
      calculated. RESULTS: Breath-hold PET showed a significant increase in SUVmax, as
      compared with free-breathing PET (8.26 +/- 4.59 vs. 11.25 +/- 7.24, P < 0.0001).
      The mean difference in SUVmax was 39.5% +/- 43.4%, and the range was 2.9%-248.3%.
      The difference in SUVmax was significant when compared between tumors in the
      upper lung (n = 22) and tumors in the lower lung (n = 25) (24.4% +/- 17.7% vs.
      52.9% +/- 54.3%, P = 0.0077). The mean tumor size of the group with a high SUVmax
      difference (n = 13) was significantly smaller than that of the group with a low
      SUVmax difference (n = 34) (2.45 +/- 0.87 cm vs. 3.21 +/- 1.22 cm, P = 0.043),
      using a cutoff of 39.5%. CONCLUSION: The single 20-s acquisition of breath-hold
      PET/CT enabled more precise measurement of SUVmax, especially in the lower lung
      field and for small tumors, which may be affected by respiratory motion. This
      technique is feasible in the clinical setting and requires only a minor increase
      in examination time.

PMID- 19759112
TI  - Functional images reflect aggressiveness of endometrial carcinoma: estrogen
      receptor expression combined with 18F-FDG PET.
AB  - The grade of histologic differentiation is one of the most important prognostic
      factors in patients with endometrial carcinoma and postoperative staging. The aim
      of this study was to investigate whether 16alpha-(18)F-fluoro-17beta-estradiol
      ((18)F-FES) and (18)F-FDG PET reflect clinicopathologic features in patients with
      endometrial tumors. METHODS: A total of 22 patients with endometrial
      adenocarcinoma and 9 with endometrial hyperplasia (mean age, 56.0 +/- 15.3 y)
      underwent (18)F-FES PET for estrogen receptor imaging and (18)F-FDG PET. Regional
      values of tracer uptake were evaluated using standardized uptake value (SUV) and
      the SUV ratio of (18)F-FDG to (18)F-FES. The accuracy for predicting tumor
      aggressiveness defined as high-risk carcinoma (International Federation of
      Gynecology and Obstetrics [FIGO] stage >or= Ic or histologic grade >or= 2), low
      risk carcinoma (FIGO stage <or= Ib and grade 1), and hyperplasia was compared for
      each PET parameter using receiver-operating-characteristic (ROC) analysis. The
      diagnostic accuracy of MRI findings for clinical staging was also compared.
      RESULTS: Although the SUV for (18)F-FDG was significantly lower in endometrial
      hyperplasia than in carcinoma, a significant difference between high-risk and low
      risk carcinoma was observed only in SUV for (18)F-FES. High-risk carcinoma showed
      a significantly greater (18)F-FDG-to-(18)F-FES ratio (3.6 +/- 2.1) than did low
      risk carcinoma (1.3 +/- 0.5, P < 0.01) and hyperplasia (0.3 +/- 0.1, P < 0.005).
      Low-risk carcinoma showed a significantly higher (18)F-FDG-to-(18)F-FES ratio
      than hyperplasia (P < 0.0001). In ROC analysis, the most accurate diagnostic PET
      parameter for predicting high-risk and low-risk carcinoma was the (18)F-FDG-to
      (18)F-FES ratio. The optimal (18)F-FDG/(18)F-FES cutoff value of 2.0, determined
      by ROC analysis, revealed 73% sensitivity, 100% specificity, and 86% accuracy,
      which was better than the 77% accuracy for MRI. The (18)F-FDG-to-(18)F-FES ratio
      of 0.5 yielded a correct diagnosis for carcinoma from hyperplasia with 100%
      accuracy. CONCLUSION: Endometrial carcinoma reduces estrogen dependency with
      accelerated glucose metabolism as it progresses to a higher stage or grade. (18)F
      FES and (18)F-FDG PET studies provide a new index of the (18)F-FDG-to-(18)F-FES
      ratio, which is considered the most informative index reflecting tumor
      aggressiveness. This index will be useful for making noninvasive diagnoses and
      deciding the appropriate therapeutic strategy for patients with endometrial
      carcinoma.

PMID- 19759113
TI  - Observer variation in interpreting 18F-FDG PET/CT findings for lymphoma staging.
AB  - Many studies demonstrate a high accuracy for PET in staging lymphoma, but few
      assess observer variation. This study quantified agreement for staging lymphoma
      with PET/CT. METHODS: The PET/CT images of 100 patients with lymphoma who had
      been referred for staging were reviewed by 3 experienced observers, with 2
      observers reviewing each series a second time. Ann Arbor stage and individual
      nodal and extranodal regions were assessed. Weighted kappa (kappa(w)) and
      intraclass correlation coefficient were used to compare ratings. RESULTS: Intra-
      and interobserver agreement was high for Ann Arbor stage (kappa(w) = 0.79-0.91),
      number of nodal regions involved (intraclass correlation coefficient, 0.83-0.93),
      and presence of extranodal disease (kappa = 0.74-0.86). High agreement was also
      observed for all nodal regions (kappa(w) > 0.60) except hilar (kappa(w) = 0.56
      0.82) and infraclavicular (kappa(w) = 0.14-0.55). Lower agreement was observed
      for bowel involvement (kappa(w) = 0.37-0.71). CONCLUSION: Experienced observers
      had a high level of agreement using PET/CT for lymphoma staging, supporting its
      use as a robust noninvasive staging tool. Further research is needed to evaluate
      observer variability for restaging during and after chemotherapy.

PMID- 19759114
TI  - Salivary gland side effects commonly develop several weeks after initial
      radioactive iodine ablation.
AB  - Salivary gland side effects (SSEs) can be a source of significant morbidity in
      thyroid cancer patients receiving radioactive iodine (RAI) for remnant ablation
      or therapy. However, the incidence, time course, and ultimate resolution of SSEs
      that develop in the first few months after a single administered activity of RAI
      for remnant ablation has not be adequately defined. METHODS: We retrospectively
      reviewed the clinical records of patients after RAI remnant ablation (RRA) to
      determine the incidence of salivary gland-related side effects reported within
      the first year of RRA, the dose-response relationship between administered
      activity and specific SSEs, and the incidence of specific SSEs based on the
      method of preparation for remnant ablation (recombinant human thyroid-stimulating
      hormone [rhTSH] vs. traditional thyroid hormone withdrawal [THW]). RESULTS: SSEs
      were reported within the first year of RAI ablation in 39% of a cohort of 262
      patients (66% women, 93% papillary thyroid cancer; median dose, 5,217 MBq [141
      mCi]). Persistent side effects were noted after a median of 7 y in 5% or less of
      the entire cohort. However, when side effects developed in patients during the
      first year, the incidence of persistence of the symptom at last follow-up ranged
      from 5% to 13%. A statistically significant dose response was seen between
      administered activity of RAI and development of salivary gland swelling (P =
      0.001, logistic dose-response curve) but not with dry mouth (P = 0.63), altered
      taste (P = 0.27), or salivary gland pain (P = 0.152). SSEs developed in 14% of
      patients receiving administered activities of 1,110 MBq (30 mCi); administered
      activities of 2,775 MBq (75 mCi) or more were associated with symptoms in 40% of
      patients (P = 0.046). Despite receiving a statistically higher administered
      activity (5,661 +/- 2,997 MBq [153 +/- 81 mCi] for THW vs. 4,958 +/- 2,294 MBq
      [134 +/- 62 mCi] for rhTSH), THW was associated with a lower rate of salivary
      gland swelling than the rhTSH preparation (20% vs. 10%; P = 0.017), without
      differences in the development of dry mouth, altered taste, or salivary gland
      pain. CONCLUSION: Although SSEs occurred in 39% of patients after routine RRA,
      they were usually transient, so that the overall incidence of persistent side
      effects at a median follow-up of 7 y was only 5%. Even though the risk for
      persistent side effects is rather small, these data do emphasize the need to
      select patients carefully for RRA who are thought to be at moderate to high risk
      for recurrence and to use the minimally effective dose of RAI activity, in an
      attempt to maximize the potential benefit while minimizing the risk for adverse
      events for an individual patient.

PMID- 19759115
TI  - A biomathematical modeling approach to central nervous system radioligand
      discovery and development.
AB  - The development of a successful PET or SPECT molecular imaging probe is a
      complex, time-consuming, and expensive process that suffers from high attrition.
      To address this problem, we have developed a biomathematical modeling approach
      that aims to predict the in vivo performance of radioligands directly from in
      silico/in vitro data. METHODS: The method estimates the in vivo nondisplaceable
      and total uptake of a ligand in a target tissue using a standard input function
      and a 1-tissue-compartment model with a parsimonious parameter set (influx rate
      constant K(1), efflux rate constant k(2), and binding potential BP(ND)) whose
      values are predicted from in silico/in vitro data including lipophilicity,
      molecular volume, free fraction in plasma and tissue, target density, affinity,
      perfusion, capillary surface area, and apparent aqueous volume in plasma and
      tissue. The coefficient of variation of the BP(ND) (%COV[BP(ND)]) metric, derived
      from Monte Carlo simulations, is used to estimate the in vivo performance of
      candidate compounds. A total of 28 compounds for 10 targets was evaluated using
      our method to predict their in vivo performance and validated against measured in
      vivo PET data in the Yorkshire/Danish Landrace pig. RESULTS: The predicted K(1),
      k(2), and BP(ND) values were generally consistent with the values estimated from
      in vivo PET data. The model resulted in small %COV[BP(ND)] values for widely
      accepted good ligands such as (11)C-flumazenil (2.02%) and (11)C-raclopride
      (2.55%), whereas higher values resulted from poor ligands such as (11)C-(R)
      PK11195 (13.34%). Of 4 candidates for the GlyT1 transporter, the model selected
      (11)C-GSK931145 (2.11%) as the most promising ligand, which was consistent with
      historical decisions made on the in vivo PET data. CONCLUSION: A biomathematical
      modeling approach has the potential to predict the in vivo performance of ligands
      from in silico/in vitro data and aid in the development of molecular imaging
      probes.

PMID- 19759116
TI  - Melanin-targeted preclinical PET imaging of melanoma metastasis.
AB  - Dialkylamino-alkyl-benzamides possess an affinity for melanin, suggesting that
      labeling of such benzamides with (18)F could potentially produce melanin-targeted
      PET probes able to identify melanotic melanoma metastases in vivo with high
      sensitivity and specificity. METHODS: In this study, N-[2-(diethylamino)ethyl]-4
      (18)F-fluorobenzamide ((18)F-FBZA) was synthesized via a 1-step conjugation
      reaction. The sigma-receptor binding affinity of (19)F-FBZA was determined along
      with the in vitro cellular uptake of radiofluorinated (18)F-FBZA in B16F10 cells.
      In vivo distribution and small-animal PET studies were conducted on mice bearing
      B16F10 melanoma, A375M amelanotic melanoma, and U87MG tumors, and comparative
      studies were performed with (18)F-FDG PET in the melanoma models. RESULTS: In
      vitro, uptake of (18)F-FBZA was significantly higher in B16F10 cells treated with
      l-tyrosine (P < 0.001). In vivo, (18)F-FBZA displayed significant tumor uptake;
      at 2 h, 5.94 +/- 1.83 percentage injected dose (%ID) per gram was observed in
      B16F10 tumors and only 0.75 +/- 0.09 %ID/g and 0.56 +/- 0.13 %ID/g was observed
      in amelanotic A375M and U87MG tumors, respectively. Lung uptake was significantly
      higher in murine lungs bearing melanotic B16F10 pulmonary metastases than in
      normal murine lungs (P < 0.01). Small-animal PET clearly identified melanotic
      lesions in both primary and pulmonary metastasis B16F10 tumor models.
      Coregistered micro-CT with small-animal PET along with biopsies further confirmed
      the presence of tumor lesions in the mouse lungs. CONCLUSION: (18)F-FBZA
      specifically targets primary and metastatic melanotic melanoma lesions with high
      tumor uptake and may have translational potential.

PMID- 19759117
TI  - 18F-FDG PET/CT identifies patients at risk for future vascular events in an
      otherwise asymptomatic cohort with neoplastic disease.
AB  - Our objective was to evaluate the association of arterial (18)F-FDG uptake and
      calcifications in large arteries as detected by (18)F-FDG PET/CT with the
      subsequent occurrence of vascular events in otherwise asymptomatic cancer
      patients. METHODS: Clinical follow-up information was obtained for 932 cancer
      patients examined with whole-body (18)F-FDG PET/CT (median follow-up time, 29
      mo). Among this cohort, 279 patients had died from their oncologic disease. In 15
      of 932 patients (1.6%), a vascular event, defined as ischemic stroke, myocardial
      infarction, or revascularization, was registered. The maximal standardized uptake
      value (SUV) was divided by the blood-pool SUV, yielding a target-to-background
      ratio (TBR) for each arterial segment. The mean TBR as well as a calcified plaque
      sum score per patient were calculated in the major vessels: ascending,
      descending, and abdominal aorta, aortic arch, as well as iliac and carotid
      arteries. RESULTS: A significant correlation was observed between mean TBR and
      calcified plaque sum (P < 0.001). Although calcified plaque sum significantly
      correlated with all conventional risk factors for vascular events, mean TBR
      correlated only with age, the male sex, and hypertension. The Cox regression
      hazard model identified a mean TBR >or= 1.7 and a calcified plaque sum >or= 15 as
      independent predictors for the occurrence of a vascular event. Patients with both
      mean TBR and calcified plaque sum above these thresholds were identified as
      having the highest risk for a future vascular event. However, a mean TBR >or= 1.7
      had greater prognostic value than did a calcified plaque sum >or= 15. CONCLUSION:
      In a large cohort of cancer patients, increased (18)F-FDG uptake in major
      arteries emerged as the strongest predictor of a subsequent vascular event.
      Concomitant severe vascular calcifications seemed to impart a particularly high
      risk. Given the small event rate in the present study, larger, prospective trials
      of patients without cancer are required to substantiate these promising results.

PMID- 19759118
TI  - Clinical imaging characteristics of the positron emission mammography camera: PEM
      Flex Solo II.
AB  - We evaluated a commercial positron emission mammography (PEM) camera, the PEM
      Flex Solo II. This system comprises two 6 x 16.4 cm detectors that scan together
      covering up to a 24 x 16.4 cm field of view (FOV). There are no specific
      standards for testing this detector configuration. We performed several tests
      important to breast imaging, and we propose tests that should be included in
      standardized testing of PEM systems. METHODS: We measured spatial resolution,
      uniformity, counting- rate linearity, recovery coefficients, and quantification
      accuracy using the system's software. Image linearity and coefficient of
      variation at the edge of the FOV were also characterized. Anecdotal examples of
      clinical patient data are presented. RESULTS: The spatial resolution was 2.4 mm
      in full width at half maximum for image planes parallel to the detector faces.
      The background variability was approximately 5%, and quantification accuracy and
      recovery coefficients varied within the FOV. Positioning linearity began at
      approximately 13 mm from the edge of the detector housing. The coefficient of
      variation was significantly higher close to the edge of the FOV because of
      limited sensitivity in these image planes. CONCLUSION: A reconstructed spatial
      resolution of 2.4 mm represented a significant improvement over conventional
      whole-body PET scanners and should reduce the lower threshold on lesion size and
      tracer uptake for detection in the breast. Limited-angle tomography and a lack of
      data corrections result in spatially variable quantitative results. PEM
      acquisition geometry limits sampling statistics at the chest-wall edge of the
      camera, resulting in high variance in that portion of the image. Example patient
      images demonstrate that lesions can be detected at the chest-wall edge despite
      variance artifacts, and fine structure is visualized routinely throughout the FOV
      in the focal plane. The PEM Flex camera should enable the functional imaging of
      breast cancer earlier in the disease process than whole-body PET.

PMID- 19759119
TI  - Multispectral fluorescence imaging.
AB  - Multispectral fluorescence imaging (MSFI) is a rapidly growing field with broad
      applications in both preclinical and clinical settings. Application of this novel
      technology in small-animal imaging and microscopy produces enhanced sensitivity
      and reliable quantification and resolves multiple simultaneous signals. MSFI flow
      cytometry can quantify multiple fluorescent parameters with morphologic or
      subcellular spatial details on millions of cells. MSFI has the potential to
      improve the accuracy of disease detection or differentiation and intrasurgical
      metastatic diagnosis, guide neurosurgeries, and monitor treatment response.

PMID- 19759121
TI  - In vivo optical imaging of cellular inflammatory response in granuloma formation
      using fluorescence-labeled macrophages.
AB  - Near-infrared imaging such as fluorescence reflectance imaging (FRI) and
      fluorescence-mediated tomography (FMT) yields high signal-to-noise ratios (SNRs)
      and should thus be well suited for cell-tracking studies. Extravasation of
      monocytes or macrophages (Ms) is one of the earliest events in inflammation. The
      purpose of this study was to assess whether FRI and FMT allow for the
      visualization and quantification of early inflammatory processes by tracing the
      migration of fluorescence-labeled murine Ms in a cutaneous granuloma model.
      METHODS: Ms were labeled with a membrane-selective carbocyanine dye (1,1
      dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide [DiR]). Cellular
      viability and function (nitric oxide production, phagocytosis, adherence) were
      assessed in vitro. Local inflammation was induced in mice by the subcutaneous
      injection of polyacrylamide gel pellets including or excluding a strong
      inflammatory stimulus (lipopolysaccharide). Labeled Ms were injected
      intravenously, and FRI and FMT were performed up to 7 d. SNRs were calculated for
      the pellets, and the 3-dimensional distribution of Ms was assessed using FMT.
      Cells were harvested from gel pellets and analyzed by flow cytometry. RESULTS:
      DiR labeling did not affect cell viability or cell function. FRI revealed the
      migration of labeled Ms into gel pellets and the homing of Ms to different body
      compartments. The lipopolysaccharide-containing pellets exhibited significantly
      higher SNRs than did pellets without lipopolysaccharide. FMT showed that Ms
      distributed mainly in the periphery of the pellets. The cellular infiltrates
      extracted from the harvested pellets revealed the presence of approximately 10%
      23% DiR-positive Ms-expressing typical markers, confirming the transendothelial
      migration of injected Ms. CONCLUSION: The tagging of Ms with DiR allows the
      noninvasive tracking of inflammatory cells for several days in vivo. FRI and FMT
      are versatile techniques to monitor and quantify cellular inflammatory responses
      in vivo.

PMID- 19759122
TI  - 131I-6beta-iodomethyl-19-norcholesterol SPECT/CT for primary aldosteronism
      patients with inconclusive adrenal venous sampling and CT results.
AB  - The 2 main causes of primary aldosteronism (PA) are aldosterone-producing adenoma
      (APA) and idiopathic adrenal hyperplasia (IAH). Dexamethasone-suppression (131)I
      6beta-iodomethyl-19-norcholesterol (NP-59) adrenal scintigraphy can assess the
      functioning of the adrenal cortex. This study evaluated the diagnostic usefulness
      of NP-59 SPECT/CT in differentiating APA from IAH and in predicting
      postadrenalectomy clinical outcome for PA patients who had inconclusive adrenal
      venous sampling (AVS) and CT results. METHODS: We retrospectively reviewed the 31
      adrenal lesions of 27 patients (age range, 33-71 y; mean age +/- SD, 50.4 +/-
      10.9 y) who had been clinically confirmed (by saline infusion and captopril
      tests) to have PA, had inconclusive CT and AVS test results, and had undergone NP
      59 imaging before adrenalectomy. The accuracy of NP-59 imaging was determined by
      comparison with histopathologic findings. RESULTS: NP-59 SPECT/CT gave us 18 true
      positive, 3 false-positive, 6 true-negative, and 4 false-negative results.
      Compared with planar imaging, SPECT/CT significantly improved diagnostic accuracy
      and prognostic predicting ability (P = 0.0390 and P = 0.0141, respectively). The
      NP-59 results were negative for 7 of the 23 patients with unilateral adrenal
      lesions, and none of these 7 patients had shown postsurgical clinical
      improvement. CONCLUSION: NP-59 SPECT/CT is an effective imaging tool for
      differentiating APA from IAH in PA patients whose CT and AVS results are
      inconclusive. Our results suggest that patients with presurgically negative NP-59
      results should be treated medically and that noninvasive NP-59 SPECT/CT may be
      suited for use as the first lateralization modality after CT in patients with
      clinically confirmed PA.

PMID- 19759123
TI  - Population response to contextual influences in the primary visual cortex.
AB  - Collinear proximal flankers can facilitate the detection of a low-contrast target
      or generate false-alarm target detection in the absence of a target. Although
      these effects are known to involve subthreshold neuronal interactions beyond the
      classical receptive field, the underlying neuronal mechanisms are not fully
      understood. Here, we used voltage-sensitive dye imaging that emphasizes
      subthreshold population activity, at high spatial and temporal resolution and
      imaged the visual cortex of fixating monkeys while they were presented with a low
      contrast Gabor target, embedded within collinear or orthogonal flankers. We found
      that neuronal activity at the target site in area primary visual cortex increased
      and response latency decreased due to spatial spread of activation from the
      flankers' site. This increased activity was smaller than expected by a linear
      summation. The presentation of flankers alone induced strong spatial filling-in
      at the target site. Importantly, the increased neuronal activity at the target
      site was synchronized over time, both locally and with neuronal population at the
      flanker's site. This onset synchronization was higher for collinear than for
      orthogonal flankers. We further show that synchrony is a superior code over
      amplitude, for discriminating collinear from orthogonal pattern. These results
      suggest that population synchrony can serve as a code to discriminate contextual
      effects.

PMID- 19759124
TI  - Perceptual expectation evokes category-selective cortical activity.
AB  - Selective visual attention directed to a location (even in the absence of a
      stimulus) increases activity in the corresponding regions of visual cortex and
      enhances the speed and accuracy of target perception. We further explored top
      down influences on perceptual representations by manipulating observers'
      expectations about the category of an upcoming target. Observers viewed a display
      in which an object (either a face or a house) gradually emerged from a state of
      phase-scrambled noise; a cue established expectation about the object category.
      Observers were faster to categorize faces (gender discrimination) or houses
      (structural discrimination) when the category of the partially scrambled object
      matched their expectation. Functional magnetic resonance imaging revealed that
      this expectation was associated with anticipatory increases in category-specific
      visual cortical activity, even in the absence of object- or category-specific
      visual information. Expecting a face evoked increased activity in face-selective
      cortical regions in the fusiform gyrus and superior temporal sulcus. Conversely,
      expecting a house increased activity in parahippocampal gyrus. These results
      suggest that visual anticipation facilitates subsequent perception by recruiting,
      in advance, the same cortical mechanisms as those involved in perception.

PMID- 19759125
TI  - Dual effect of glutamate on GABAergic interneuron survival during cerebral cortex
      development in mice neonates.
AB  - In term and preterm neonates, massive glutamate release can lead to excitotoxic
      white-matter and cortical lesions. Because of its high permeability toward
      calcium, the N-methyl-D-aspartic acid (NMDA) receptor is thought to play an
      important role in excitotoxic lesions and NMDA antagonists therefore hold promise
      for neuroprotection. We found that, in neonatal mouse cortex, a given NMDA
      concentration exerted either excitotoxic or antiapoptotic effects depending on
      the cortical layers. In layer VI, NMDA led to excitotoxicity, sustained calcium
      mobilization, and necrosis of Gad67GFP neurons. In the immature layers II-IV,
      NMDA decreased apoptosis and induced transient calcium mobilization. The NMDA
      antagonist MK801 acted as a potent caspase-3 activator in immature layers II-IV
      and affected gamma aminobutyric acid (GABA)ergic interneurons. The apoptotic
      effect of MK801-induced BAX expression, mitochondrial potential collapse and
      caspase-9 activation. In vivo Bax small interfering ribonucleic acid and a
      caspase-9 inhibitor abrogated MK801-induced apoptosis and pyknotic nucleus
      formation. Ketamine, an anesthetic with NMDA antagonist properties, mimicked the
      apoptotic effects of MK801. These data indicate a dual effect of glutamate on
      survival of immature and mature GABAergic neurons and suggest that ketamine may
      induce apoptosis of immature GABAergic neurons.

PMID- 19759126
TI  - Cleavage specificity of the UL48 deubiquitinating protease activity of human
      cytomegalovirus and the growth of an active-site mutant virus in cultured cells.
AB  - The human cytomegalovirus (HCMV) open reading frame UL48 encodes a 253-kDa
      tegument protein that is closely associated with the capsid and was recently
      shown to have ubiquitin-specific protease activity (J. Wang, A. N. Loveland, L.
      M. Kattenhorn, H. L. Ploegh, and W. Gibson, J. Virol. 80:6003-6012, 2006). Here,
      we examined the cleavage specificity of this deubiquitinase (DUB) and replication
      characteristics of an active-site mutant virus. The purified catalytic domain of
      the UL48 DUB (1 to 359 amino acids), corresponding to the herpes simplex virus
      UL36(USP) DUB (L. M. Kattenhorn, G. A. Korbel, B. M. Kessler, E. Spooner, and H.
      L. Ploegh, Mol. Cell 19:547-557, 2005), efficiently released ubiquitin but not
      ubiquitin-like modifications from a hemagglutinin peptide substrate. Mutating the
      active-site residues Cys24 or His162 (C24S and H162A, respectively) abolished
      this activity. The HCMV UL48 and HSV UL36(USP) DUBs cleaved both Lys48- and Lys63
      linked ubiquitin dimers and oligomers, showing more activity toward Lys63
      linkages. The DUB activity of the full-length UL48 protein immunoprecipitated
      from virus-infected cells also showed a better cleavage of Lys63-linked
      ubiquitinated substrates. An HCMV (Towne) mutant virus in which the UL48 DUB
      activity was destroyed [UL48(C24S)] produced 10-fold less progeny virus and
      reduced amounts of viral proteins compared to wild-type virus at a low
      multiplicity of infection. The mutant virus also produced perceptibly less
      overall deubiquitination than the wild-type virus. Our findings demonstrate that
      the HCMV UL48 DUB contains both a ubiquitin-specific carboxy-terminal hydrolase
      activity and an isopeptidase activity that favors ubiquitin Lys63 linkages and
      that these activities can influence virus replication in cultured cells.

PMID- 19759127
TI  - Maribavir inhibits epstein-barr virus transcription in addition to viral DNA
      replication.
AB  - Although many drugs inhibit the replication of Epstein-Barr virus (EBV) in cell
      culture systems, there is still no drug that is effective and approved for use in
      primary EBV infection. More recently, maribavir (MBV), an l-ribofuranoside
      benzimidazole, has been shown to be a potent and nontoxic inhibitor of EBV
      replication and to have a mode of action quite distinct from that of acyclic
      nucleoside analogs such as acyclovir (ACV) that is based primarily on MBV's
      ability to block the phosphorylation of target proteins by EBV and human
      cytomegalovirus protein kinases. However, since the antiviral mechanisms of the
      drug are complex, we have carried out a comprehensive analysis of the effects of
      MBV on the RNA expression levels of all EBV genes with a quantitative real-time
      reverse transcription-PCR-based array. We show that in comparisons with ACV, the
      RNA expression profiles produced by the two drugs are entirely different, with
      MBV causing a pronounced inhibition of multiple viral mRNAs and with ACV causing
      virtually none. The results emphasize the different modes of action of the two
      drugs and suggest that the action of MBV may be linked to indirect effects on the
      transcription of EBV genes through the interaction of BGLF4 with multiple viral
      proteins.

PMID- 19759128
TI  - Cell cycle arrest by transforming growth factor beta1 enhances replication of
      respiratory syncytial virus in lung epithelial cells.
AB  - Respiratory syncytial virus (RSV) is a common respiratory viral infection in
      children which is associated with immune dysregulation and subsequent induction
      and exacerbations of asthma. We recently reported that treatment of primary human
      epithelial cells (PHBE cells) with transforming growth factor beta (TGF-beta)
      enhanced RSV replication. Here, we report that the enhancement of RSV replication
      is mediated by induction of cell cycle arrest. These data were confirmed by using
      pharmacologic inhibitors of cell cycle progression, which significantly enhanced
      RSV replication. Our data also showed that RSV infection alone resulted in cell
      cycle arrest in A549 and PHBE cells. Interestingly, our data showed that RSV
      infection induced the expression of TGF-beta in epithelial cells. Blocking of TGF
      beta with anti-TGF-beta antibody or use of a specific TGF-beta receptor signaling
      inhibitor resulted in rescue of the RSV-induced cell cycle arrest, suggesting an
      autocrine mechanism. Collectively, our data demonstrate that RSV regulates the
      cell cycle through TGF-beta in order to enhance its replication. These findings
      identify a novel pathway for upregulation of virus replication and suggest a
      plausible mechanism for association of RSV with immune dysregulation and asthma.

PMID- 19759129
TI  - Transcriptional analysis of the adeno-associated virus integration site.
AB  - The nonpathogenic human adeno-associated virus type 2 (AAV-2) has adopted a
      unique mechanism to site-specifically integrate its genome into the human MBS85
      gene, which is embedded in AAVS1 on chromosome 19. The fact that AAV has evolved
      to integrate into this ubiquitously transcribed region and that the chromosomal
      motifs required for integration are located a few nucleotides upstream of the
      translation initiation start codon of MBS85 suggests that the transcriptional
      activity of MBS85 might influence site-specific integration and thus might be
      involved in the evolution of this mechanism. In order to begin addressing this
      question, we initiated the characterization of the human MBS85 promoter region
      and compared its transcriptional activity to that of the AAV-2 p5 promoter. Our
      results clearly indicate that AAVS1 is defined by a complex transcriptional
      environment and that the MBS85 promoter shares key regulatory elements with the
      viral p5 promoter. Furthermore, we provide evidence for bidirectional MBS85
      promoter activity and demonstrate that the minimal motifs required for AAV site
      specific integration are present in the 5' untranslated region of the gene and
      play a posttranscriptional role in the regulation of MBS85 expression. These
      findings should provide a framework to further elucidate the complex interactions
      between the virus and its cellular host in this unique pathway to latency.

PMID- 19759130
TI  - Dephosphorylation of eIF2alpha mediated by the gamma134.5 protein of herpes
      simplex virus 1 facilitates viral neuroinvasion.
AB  - The gamma(1)34.5 protein, a virulence factor of herpes simplex viruses, redirects
      protein phosphatase 1 to dephosphorylate the alpha subunit of translation
      initiation factor 2 (eIF2alpha). Additionally, it inhibits the induction of
      antiviral genes by TANK-binding kinase 1. Nevertheless, its precise role in vivo
      remains to be established. Here we show that eIF2alpha dephosphorylation by
      gamma(1)34.5 is crucial for viral neuroinvasion. V(193)E and F(195)L
      substitutions in gamma(1)34.5 abrogate viral replication in the eye and spread to
      the trigeminal ganglia and brain. Intriguingly, inhibition of antiviral gene
      induction by gamma(1)34.5 is not sufficient to exhibit viral virulence.

PMID- 19759131
TI  - Interaction of the vaccinia virus RNA polymerase-associated 94-kilodalton protein
      with the early transcription factor.
AB  - A multisubunit RNA polymerase (RPO) encoded by vaccinia virus (VACV), in
      conjunction with specific factors, transcribes early, intermediate, and late
      viral genes. However, an additional virus-encoded polypeptide referred to as the
      RPO-associated protein of 94 kDa (RAP94) is tightly bound to the RPO for the
      transcription of early genes. Unlike the eight RPO core subunits, RAP94 is
      synthesized exclusively at late times after infection. Furthermore, RAP94 is
      necessary for the packaging of RPO and other components needed for early
      transcription in assembling virus particles. The direct association of RAP94 with
      NPH I, a DNA-dependent ATPase required for transcription termination, and the
      multifunctional poly(A) polymerase small subunit/2'-O
      methyltransferase/elongation factor was previously demonstrated. That RAP94
      provides a structural and functional link between the core RPO and the VACV early
      transcription factor (VETF) has been suspected but not previously demonstrated.
      Using VACV recombinants that constitutively or inducibly express VETF subunits
      and RAP94 with affinity tags, we showed that (i) VETF associates only with RPO
      containing RAP94 in vivo and in vitro, (ii) the association of RAP94 with VETF
      requires both subunits of the latter, (iii) neither viral DNA nor other virus
      encoded late proteins are required for the interaction of RAP94 with VETF and
      core RPO subunits, (iv) different domains of RAP94 bind VETF and core subunits of
      RPO, and (v) NPH I and VETF bind independently and possibly simultaneously to the
      N-terminal region of RAP94. Thus, RAP94 provides the bridge between the RPO and
      proteins needed for transcription initiation, elongation, and termination.

PMID- 19759132
TI  - Fusion between perinuclear virions and the outer nuclear membrane requires the
      fusogenic activity of herpes simplex virus gB.
AB  - Herpesviruses cross nuclear membranes (NMs) in two steps, as follows: (i) capsids
      assemble and bud through the inner NM into the perinuclear space, producing
      enveloped virus particles, and (ii) the envelopes of these virus particles fuse
      with the outer NM. Two herpes simplex virus (HSV) glycoproteins, gB and gH (the
      latter, likely complexed as a heterodimer with gL), are necessary for the second
      step of this process. Mutants lacking both gB and gH accumulate in the
      perinuclear space or in herniations (membrane vesicles derived from the inner
      NM). Both gB and gH/gL are also known to act directly in fusing the virion
      envelope with host cell membranes during HSV entry into cells, i.e., both
      glycoproteins appear to function directly in different aspects of the membrane
      fusion process. We hypothesized that HSV gB and gH/gL also act directly in the
      membrane fusion that occurs during virus egress from the nucleus. Previous
      studies of the role of gB and gH/gL in nuclear egress involved HSV gB and gH null
      mutants that could potentially also possess gross defects in the virion envelope.
      Here, we produced recombinant HSV-expressing mutant forms of gB with single amino
      acid substitutions in the hydrophobic "fusion loops." These fusion loops are
      thought to play a direct role in membrane fusion by insertion into cellular
      membranes. HSV recombinants expressing gB with any one of four fusion loop
      mutations (W174R, W174Y, Y179K, and A261D) were unable to enter cells. Moreover,
      two of the mutants, W174Y and Y179K, displayed reduced abilities to mediate HSV
      cell-to-cell spread, and W174R and A261D exhibited no spread. All mutant viruses
      exhibited defects in nuclear egress, enveloped virions accumulated in herniations
      and in the perinuclear space, and fewer enveloped virions were detected on cell
      surfaces. These results support the hypothesis that gB functions directly to
      mediate the fusion between perinuclear virus particles and the outer NM.

PMID- 19759133
TI  - Transgenic expression of the 3D polymerase inhibits Theiler's virus infection and
      demyelination.
AB  - The RNA-dependent RNA polymerase 3D(pol) is required for the elongation of
      positive- and negative-stranded picornavirus RNA. During the course of
      investigating the effect of the transgenic expression of viral genes on the host
      immune response, we evaluated the viral load present in the host after infection.
      To our surprise, we found that 3D transgenic expression in genetically
      susceptible FVB mice led to substantially lower viral loads after infection with
      Theiler's murine encephalomyelitis virus (TMEV). As a result, spinal cord damage
      caused by chronic viral infection in the central nervous system was reduced in
      FVB mice that expressed 3D. This led to the preservation of large-diameter axons
      and motor function in these mice. The 3D transgene also lowered early viral loads
      when expressed in FVB-D(b) mice resistant to persistent TMEV infection. The
      protective effect of 3D transgenic expression was not altered in FVB-Rag(-/-).3D
      mice that are deficient in T and B cells, thus ruling out a mechanism by which
      the overexpression of 3D enhanced the adaptive immune clearance of the virus.
      Understanding how endogenously overexpressed 3D polymerase inhibits viral
      replication may lead to new strategies for targeting therapies to all
      picornaviruses.

PMID- 19759134
TI  - Association of the pr peptides with dengue virus at acidic pH blocks membrane
      fusion.
AB  - Flavivirus assembles into an inert particle that requires proteolytic activation
      by furin to enable transmission to other hosts. We previously showed that
      immature virus undergoes a conformational change at low pH that renders it
      accessible to furin (I. M. Yu, W. Zhang, H. A. Holdaway, L. Li, V. A.
      Kostyuchenko, P. R. Chipman, R. J. Kuhn, M. G. Rossmann, and J. Chen, Science
      319:1834-1837, 2008). Here we show, using cryoelectron microscopy, that the
      structure of immature dengue virus at pH 6.0 is essentially the same before and
      after the cleavage of prM. The structure shows that after cleavage, the
      proteolytic product pr remains associated with the virion at acidic pH, and that
      furin cleavage by itself does not induce any major conformational changes. We
      also show by liposome cofloatation experiments that pr retention prevents
      membrane insertion, suggesting that pr is present on the virion in the trans
      Golgi network to protect the progeny virus from fusion within the host cell.

PMID- 19759135
TI  - Persistence of transgene expression influences CD8+ T-cell expansion and
      maintenance following immunization with recombinant adenovirus.
AB  - Previous studies determined that the CD8(+) T-cell response elicited by
      recombinant adenovirus exhibited a protracted contraction phase that was
      associated with long-term presentation of antigen. To gain further insight into
      this process, a doxycycline-regulated adenovirus was constructed to enable
      controlled extinction of transgene expression in vivo. We investigated the impact
      of premature termination of transgene expression at various time points (day 3 to
      day 60) following immunization. When transgene expression was terminated before
      the maximum response had been attained, overall expansion was attenuated,
      yielding a small memory population. When transgene expression was terminated
      between day 13 and day 30, the memory population was not sustained, demonstrating
      that the early memory population was antigen dependent. Extinction of transgene
      expression at day 60 had no obvious impact on memory maintenance, indicating that
      maintenance of the memory population may ultimately become independent of
      transgene expression. Premature termination of antigen expression had significant
      but modest effects on the phenotype and cytokine profile of the memory
      population. These results offer new insights into the mechanisms of memory CD8(+)
      T-cell maintenance following immunization with a recombinant adenovirus.

PMID- 19759136
TI  - The CDK inhibitor p21Cip1/WAF1 is induced by FcgammaR activation and restricts
      the replication of human immunodeficiency virus type 1 and related primate
      lentiviruses in human macrophages.
AB  - Macrophages are major targets of human immunodeficiency virus type 1 (HIV-1). We
      have previously shown that aggregation of activating immunoglobulin G Fc
      receptors (FcgammaR) by immune complexes inhibits reverse transcript accumulation
      and integration of HIV-1 and related lentiviruses in monocyte-derived
      macrophages. Here, we show that FcgammaR-mediated restriction of HIV-1 is not due
      to enhanced degradation of incoming viral proteins or cDNA and is associated to
      the induction of the cyclin-dependent kinase inhibitor p21(Cip1/WAF1) (p21).
      Small interfering RNA-mediated p21 knockdown rescued viral replication in
      FcgammaR-activated macrophages and enhanced HIV-1 infection in unstimulated
      macrophages by increasing reverse transcript and integrated DNA levels. p21
      induction by other stimuli, such as phorbol myristate acetate and the histone
      deacetylase inhibitor MS-275, was also associated with preintegrative blocks of
      HIV-1 replication in macrophages. Binding of p21 to reverse
      transcription/preintegration complex-associated HIV-1 proteins was not detected
      in yeast two-hybrid, pulldown, or coimmunoprecipitation assays, suggesting that
      p21 may affect viral replication independently of a specific interaction with an
      HIV-1 component. Consistently, p21 silencing rescued viral replication from the
      FcgammaR-mediated restriction also in simian immunodeficiency virus SIV(mac)- and
      HIV-2-infected macrophages. Our results point to a role of p21 as an inhibitory
      factor of lentiviral infection in macrophages and to its implication in FcgammaR
      mediated restriction.

PMID- 19759137
TI  - Chloroquine administration does not prevent Nipah virus infection and disease in
      ferrets.
AB  - Hendra virus and Nipah virus, two zoonotic paramyxoviruses in the genus
      Henipavirus, have recently emerged and continue to cause sporadic disease
      outbreaks in humans and animals. Mortality rates of up to 75% have been reported
      in humans, but there are presently no clinically licensed therapeutics for
      treating henipavirus-induced disease. A recent report indicated that chloroquine,
      used in malaria therapy for over 70 years, prevented infection with Nipah virus
      in vitro. Chloroquine was assessed using a ferret model of lethal Nipah virus
      infection and found to be ineffective against Nipah virus infection in vivo.

PMID- 19759138
TI  - Evolutionary dynamics of GII.4 noroviruses over a 34-year period.
AB  - Noroviruses are a major cause of epidemic gastroenteritis in children and adults,
      and GII.4 has been the predominant genotype since its first documented occurrence
      in 1987. This study examined the evolutionary dynamics of GII.4 noroviruses over
      more than three decades to investigate possible mechanisms by which these viruses
      have emerged to become predominant. Stool samples (n = 5,424) from children
      hospitalized at the Children's Hospital in Washington, DC, between 1974 and 1991
      were screened for the presence of noroviruses by a custom multiplex real-time
      reverse transcription-PCR. The complete genome sequences of five GII.4
      noroviruses (three of which predate 1987 by more than a decade) in this archival
      collection were determined and compared to the sequences of contemporary strains.
      Evolutionary analysis determined that the GII.4 VP1 capsid gene evolved at a rate
      of 4.3 x 10(-3) nucleotide substitutions/site/year. Only six sites in the VP1
      capsid protein were found to evolve under positive selection, most of them
      located in the shell domain. No unique mutations were observed in or around the
      two histoblood group antigen (HBGA) binding sites in the P region, indicating
      that this site has been conserved since the 1970s. The VP1 proteins from the 1974
      to 1977 noroviruses contained a unique sequence of four consecutive amino acids
      in the P2 region, which formed an exposed protrusion on the modeled capsid
      structure. This protrusion and other observed sequence variations did not affect
      the HBGA binding profiles of recombinant virus-like particles derived from
      representative 1974 and 1977 noroviruses compared with more recent noroviruses.
      Our analysis of archival GII.4 norovirus strains suggests that this genotype has
      been circulating for more than three decades and provides new ancestral strain
      sequences for the analysis of GII.4 evolution.

PMID- 19759139
TI  - Identification of proteins from prunus persica that interact with peach latent
      mosaic viroid.
AB  - Peach latent mosaic viroid (PLMVd) is a small, single-stranded, circular RNA
      pathogen that infects Prunus persica trees. As with all other known viroids, the
      PLMVd genome does not encode any proteins. Consequently, it must interact with
      host cellular factors in order to ensure its life cycle. With the objective of
      identifying cellular proteins that interact with PLMVd, Northwestern
      hybridizations were performed using partially purified peach leaf extracts. Mass
      spectrometric analysis of the detected RNA-protein complexes led to the
      identification of six putative RNA-binding proteins. One of these was found to be
      elongation factor 1-alpha (eEF1A), and because of its known involvement in the
      replication and translation of various RNA viruses, further characterizations
      were performed. Initially, the existence of this interaction received support
      from an experiment that immunoprecipitated the eEF1A from a crude extract of
      infected peach leaves, coupled with reverse transcription-PCR detection of the
      PLMVd. Subsequently, eEF1A interaction with PLMVd strands of both polarities was
      confirmed in vitro by electrophoresis mobility shift assays, fluorescence
      spectroscopy, and the prediction of an altered PLMVd RNase mapping profile in the
      presence of the protein. The potential contribution of eEF1A to the molecular
      biology of PLMVd, including for viroid replication, is discussed.

PMID- 19759140
TI  - Clade-specific evolution mediated by HLA-B*57/5801 in human immunodeficiency
      virus type 1 clade A1 p24.
AB  - HLA-B*57-mediated selection pressure leads to a typical escape pathway in human
      immunodeficiency virus type 1 (HIV-1) CD8 epitopes such as TW10. Whether this
      T242N pathway is shared by all clades remains unknown. We therefore assessed the
      nature of HLA-B*57 selection in a large, observational Kenyan cohort where clades
      A1 and D predominate. While T242N was ubiquitous in clade D HLA-B*57(+) subjects,
      this mutation was rare (15%) in clade A1. Instead, P243T and I247L were selected
      by clade A1-infected HLA-B*57 subjects but not by HLA-B*5801(+) subjects. Our
      data suggest that clade A1 consensus proline at Gag residue 243 might represent
      an inherent block to T242N escape in clade A1. We confirmed immunologically that
      P243T and I247L likely represent escape mutations. HLA-B*57 evolution also
      differed between clades in the KF11 and IW9 epitopes. A better understanding of
      clade-specific evolution is important for the development of HIV vaccines in
      regions with multiple clades.

PMID- 19759141
TI  - Interaction of ICP34.5 with Beclin 1 modulates herpes simplex virus type 1
      pathogenesis through control of CD4+ T-cell responses.
AB  - Autophagy is an important component of host innate and adaptive immunity to
      viruses. It is critical for the degradation of intracellular pathogens and for
      promoting antigen presentation. Herpes simplex virus type 1 (HSV-1) infection
      induces an autophagy response, but this response is antagonized by the HSV-1
      neurovirulence gene product, ICP34.5. This is due, in part, to its interaction
      with the essential autophagy protein Beclin 1 (Atg6) via the Beclin-binding
      domain (BBD) of ICP34.5. Using a recombinant virus lacking the BBD, we examined
      pathogenesis and immune responses using mouse models of infection. The BBD
      deficient virus (Delta68H) replicated equivalently to its marker-rescued
      counterpart (Delta68HR) at early times but was cleared more rapidly than
      Delta68HR from all tissues at late times following corneal infection. In
      addition, the infection of the cornea with Delta68H induced less ocular disease
      than Delta68HR. These results suggested that Delta68H was attenuated due to its
      failure to control adaptive rather than innate immunity. In support of this idea,
      Delta68H stimulated a significantly stronger CD4(+) T-cell-mediated delayed-type
      hypersensitivity response and resulted in significantly more production of gamma
      interferon and interleukin-2 from HSV-specific CD4(+) T cells than Delta68HR.
      Taken together, these data suggest a role for the BBD of ICP34.5 in precluding
      autophagy-mediated class II antigen presentation, thereby enhancing the virulence
      and pathogenesis of HSV-1.

PMID- 19759142
TI  - A novel picornavirus associated with gastroenteritis.
AB  - A novel picornavirus genome was sequenced, showing 42.6%, 35.2%, and 44.6% of
      deduced amino acid identities corresponding to the P1, P2, and P3 regions,
      respectively, of the Aichi virus. Divergent strains of this new virus, which we
      named salivirus, were detected in 18 stool samples from Nigeria, Tunisia, Nepal,
      and the United States. A statistical association was seen between virus shedding
      and unexplained cases of gastroenteritis in Nepal (P = 0.0056). Viruses with
      approximately 90% nucleotide similarity, named klassevirus, were also recently
      reported in three cases of unexplained diarrhea from the United States and
      Australia and in sewage from Spain, reflecting a global distribution and
      supporting a pathogenic role for this new group of picornaviruses.

PMID- 19759143
TI  - Ty3 nuclear entry is initiated by viruslike particle docking on GLFG
      nucleoporins.
AB  - Yeast retrotransposons form intracellular particles within which replication
      occurs. Because fungal nuclear membranes do not break down during mitosis,
      similar to retroviruses infecting nondividing cells, the cDNA produced must be
      translocated through nuclear pore complexes. The Saccharomyces cerevisiae long
      terminal repeat retrotransposon Ty3 assembles its Gag3 and Gag3-Pol3 precursor
      polyproteins into viruslike particles in association with perinuclear P-body
      foci. These perinuclear clusters of Ty3 viruslike particles localized to sites of
      clustered nuclear pore complexes (NPCs) in a nup120Delta mutant, indicating that
      Ty3 particles and NPCs interact physically. The NPC channels are lined with
      nucleoporins (Nups) with extended FG (Phe-Gly) motif repeat domains, further
      classified as FG, FxFG, or GLFG repeat types. These domains mediate partitioning
      of proteins between the cytoplasm and the nucleus. Here we have systematically
      examined the requirements for FG repeat domains in Ty3 nuclear transport. The
      GLFG domains interacted in vitro with virus-like particle Gag3, and this
      interaction was disrupted by mutations in the amino-terminal domain of Gag3,
      which is predicted to lie on the external surface of the particles. Accordingly,
      Ty3 transposition was decreased in strains with the GLFG repeats deleted. The
      spacer-nucleocapsid domain of Gag3, which is predicted to be internal to the
      particle, interacted with GLFG repeats and nucleocapsid localized to the nucleus.
      We conclude that Ty3 particle docking on nuclear pores is facilitated by
      interactions between Gag3 and GLFG Nups and that nuclear entry of the
      preintegration complex is further promoted by nuclear localization signals within
      the nucleocapsid and integrase.

PMID- 19759144
TI  - Mixed infections of Pepino mosaic virus strains modulate the evolutionary
      dynamics of this emergent virus.
AB  - Pepino mosaic virus (PepMV) is an emerging pathogen that causes severe economic
      losses in tomato crops (Solanum lycopersicum L.) in the Northern hemisphere,
      despite persistent attempts of control. In fact, it is considered one of the most
      significant viral diseases for tomato production worldwide, and it may constitute
      a good model for the analysis of virus emergence in crops. We have combined a
      population genetics approach with an analysis of in planta properties of virus
      strains to explain an observed epidemiological pattern. Hybridization analysis
      showed that PepMV populations are composed of isolates of two types (PepMV-CH2
      and PepMV-EU) that cocirculate. The CH2 type isolates are predominant; however,
      EU isolates have not been displaced but persist mainly in mixed infections. Two
      molecularly cloned isolates belonging to each type have been used to examine the
      dynamics of in planta single infections and coinfection, revealing that the CH2
      type has a higher fitness than the EU type. Coinfections expand the range of
      susceptible hosts, and coinfected plants remain symptomless several weeks after
      infection, so a potentially important problem for disease prevention and
      management. These results provide an explanation of the observed epidemiological
      pattern in terms of genetic and ecological interactions among the different viral
      strains. Thus, mixed infections appear to be contributing to shaping the genetic
      structure and dynamics of PepMV populations.

PMID- 19759145
TI  - Autographa californica multiple nucleopolyhedrovirus core gene ac96 encodes a per
      Os infectivity factor (PIF-4).
AB  - Autographa californica multiple nucleopolyhedrovirus (AcMNPV) ac96 is a core
      gene, but its role in virus replication is still unknown. To determine its role
      in the baculovirus life cycle, we used the AcMNPV bacmid system to generate an
      ac96-null virus (vAc(96)(null)). Our analyses showed that the absence of ac96
      does not affect budded virus (BV) production or viral DNA replication in infected
      Sf9 cells. Western blotting and confocal immunofluorescence analysis showed that
      AC96 is expressed in both the cytoplasm and the nucleus throughout infection. In
      addition, AC96 was detected in the envelope fractions of both BV and occlusion
      derived virus. Injection of vAc(96)(null) BV into the hemocoel killed
      Trichoplusia ni larvae as efficiently as repaired and control viruses; however,
      vAc(96)(null) was unable to infect the midgut tissue of Trichoplusia ni larvae
      when inoculated per os. Therefore, the results of this study show that ac96
      encodes a new per os infectivity factor (PIF-4).

PMID- 19759146
TI  - A proteomic approach to identify candidate substrates of human adenovirus E4orf6
      E1B55K and other viral cullin-based E3 ubiquitin ligases.
AB  - It has been known for some time that the human adenovirus serotype 5 (Ad5) E4orf6
      and E1B55K proteins work in concert to degrade p53 and to regulate selective
      export of late viral mRNAs during productive infection. Both of these functions
      rely on the formation by the Ad5 E4orf6 protein of a cullin 5-based E3 ubiquitin
      ligase complex containing elongins B and C. E1B55K is believed to function as the
      substrate recognition module for the complex and, in addition to p53, Mre11 and
      DNA ligase IV have also been identified as substrates. To discover additional
      substrates we have taken a proteomic approach by using two-dimensional difference
      gel electrophoresis to detect cellular proteins that decrease significantly in
      amount in p53-null H1299 human lung carcinoma cells after expression of E1B55K
      and E4orf6 using adenovirus vectors. Several species were detected and identified
      by mass spectroscopy, and for one of these, integrin alpha3, we went on in a
      parallel study to confirm it as a bone fide substrate of the complex (F. Dallaire
      et al., J. Virol. 83:5329-5338, 2009). Although the system has some limitations,
      it may still be of some general use in identifying candidate substrates of any
      viral cullin-based E3 ubiquitin ligase complex, and we suggest a series of
      criteria for substrate validation.

PMID- 19759147
TI  - Elevated levels of innate immune modulators in lymph nodes and blood are
      associated with more-rapid disease progression in simian immunodeficiency virus
      infected monkeys.
AB  - Cytokines and chemokines are critical for establishing tissue-specific immune
      responses and play key roles in modulating disease progression in simian
      immunodeficiency virus (SIV)-infected macaques and human immunodeficiency virus
      (HIV)-infected humans. The goal here was to characterize the innate immune
      response at different tissue sites and to correlate these responses to clinical
      outcome, initially focusing on rhesus macaques orally inoculated with SIV and
      monitored until onset of simian AIDS. Cytokine and chemokine mRNA transcripts
      were assessed at lymph nodes (LN) and peripheral blood cells utilizing
      quantitative real-time PCR at different time points postinfection. The mRNA
      expression of four immune modulators-alpha interferon (IFN-alpha), oligoadenylate
      synthetase (OAS), CXCL9, and CXCL10-was positively associated with disease
      progression within LN tissue. Elevated cytokine/chemokine expression in LN did
      not result in any observed beneficial outcome since the numbers of CXCR3(+) cells
      were not increased, nor were the SIV RNA levels decreased. In peripheral blood,
      increased OAS and CXCL10 expression were elevated in SIV(+) monkeys that progress
      the fastest to simian AIDS. Our results indicate that higher IFN-alpha, OAS,
      CXCL9, and CXCL10 mRNA expression in LN was associated with rapid disease
      progression and a LN environment that may favor SIV replication. Furthermore,
      higher expression of CXCL10 and OAS in peripheral blood could potentially serve
      as a diagnostic marker for hosts that are likely to progress to AIDS.
      Understanding the expression patterns of key innate immune modulators will be
      useful in assessing the disease state and potential rates of disease progression
      in HIV(+) patients, which could lead to novel therapy and vaccine approaches.

PMID- 19759148
TI  - Mouse hepatitis virus stem-loop 2 adopts a uYNMG(U)a-like tetraloop structure
      that is highly functionally tolerant of base substitutions.
AB  - Stem-loop 2 (SL2) of the 5'-untranslated region of the mouse hepatitis virus
      (MHV) contains a highly conserved pentaloop (C47-U48-U49-G50-U51) stacked on a 5
      bp stem. Solution nuclear magnetic resonance experiments are consistent with a 5'
      uYNMG(U)a or uCUYG(U)a tetraloop conformation characterized by an anti-C47-syn
      G50 base-pairing interaction, with U51 flipped out into solution and G50 stacked
      on A52. Previous studies showed that U48C and U48A substitutions in MHV SL2 were
      lethal, while a U48G substitution was viable. Here, we characterize viruses
      harboring all remaining single-nucleotide substitutions in the pentaloop of MHV
      SL2 and also investigate the degree to which the sequence context of key
      pentaloop point mutations influences the MHV replication phenotype. U49 or U51
      substitution mutants all are viable; C47 substitution mutants also are viable but
      produce slightly smaller plaques than wild-type virus. In contrast, G50A and G50C
      viruses are severely crippled and form much smaller plaques. Virus could not be
      recovered from G50U-containing mutants; rather, only true wild-type revertants or
      a virus, G50U/C47A, containing a second site mutation were recovered. These
      functional data suggest that the Watson-Crick edges of C47 and G50 (or A47 and
      U50 in the G50U/C47A mutant) are in close enough proximity to a hydrogen bond
      with U51 flipped out of the hairpin. Remarkably, increasing the helical stem
      stability rescues the previously lethal mutants U48C and G50U. These studies
      suggest that SL2 functions as an important, but rather plastic, structural
      element in stimulating subgenomic RNA synthesis in coronaviruses.

PMID- 19759149
TI  - Control of herpes simplex virus replication is mediated through an interferon
      regulatory factor 3-dependent pathway.
AB  - The type I interferon (IFN) cascade is critical in controlling viral replication
      and pathogenesis. Recognition pathways triggered by viral infection rapidly
      induce the type I IFN cascade, often in an IFN regulatory factor 3 (IRF-3)
      dependent fashion. This dependence predicts that loss of IRF-3 would render early
      recognition pathways inoperative and thereby impact virus replication, but this
      has not been observed previously with herpes simplex virus type 1 (HSV-1) in
      vitro. In this study, HSV-1-infected IRF-3(-/-) bone marrow-derived dendritic
      cells (BMDCs) and macrophages supported increased HSV replication compared to
      control cells. In addition, IRF-3-deficient BMDCs exhibited delayed type I IFN
      synthesis compared to control cells. However, while IFN pretreatment of IRF-3(-/
      ) BMDCs resulted in reduced virus titers, a far greater reduction was seen after
      IFN treatment of wild-type cells. This suggests that even in the presence of
      exogenously supplied IFN, IRF-3(-/-) BMDCs are inherently defective in the
      control of HSV-1 replication. Together, these results demonstrate a critical role
      for IRF-3-mediated pathways in controlling HSV-1 replication in cells of the
      murine immune system.

PMID- 19759150
TI  - The minimum replication origin of merkel cell polyomavirus has a unique large T
      antigen loading architecture and requires small T-antigen expression for optimal
      replication.
AB  - Merkel cell polyomavirus (MCV) is a recently discovered human polyomavirus
      causing the majority of human Merkel cell carcinomas. We mapped a 71-bp minimal
      MCV replication core origin sufficient for initiating eukaryotic DNA replication
      in the presence of wild-type MCV large T protein (LT). The origin includes a
      poly(T)-rich tract and eight variably oriented, GAGGC-like pentanucleotide
      sequences (PS) that serve as LT recognition sites. Mutation analysis shows that
      only four of the eight PS are required for origin replication. A single point
      mutation in one origin PS from a naturally occurring, tumor-derived virus reduces
      LT assembly on the origin and eliminates viral DNA replication. Tumor-derived LT
      having mutations truncating either the origin-binding domain or the helicase
      domain also prevent LT-origin assembly. Optimal MCV replication requires
      coexpression of MCV small T protein (sT), together with LT. An intact DnaJ domain
      on the LT is required for replication but is dispensable on the sT. In contrast,
      PP2A targeting by sT is required for enhanced replication. The MCV origin
      provides a novel model for eukaryotic replication from a defined DNA element and
      illustrates the selective pressure within tumors to abrogate independent MCV
      replication.

PMID- 19759151
TI  - Identification and characterization of broadly neutralizing human monoclonal
      antibodies directed against the E2 envelope glycoprotein of hepatitis C virus.
AB  - Nearly all livers transplanted into hepatitis C virus (HCV)-positive patients
      become infected with HCV, and 10 to 25% of reinfected livers develop cirrhosis
      within 5 years. Neutralizing monoclonal antibody could be an effective therapy
      for the prevention of infection in a transplant setting. To pursue this treatment
      modality, we developed human monoclonal antibodies (HuMAbs) directed against the
      HCV E2 envelope glycoprotein and assessed the capacity of these HuMAbs to
      neutralize a broad panel of HCV genotypes. HuMAb antibodies were generated by
      immunizing transgenic mice containing human antibody genes (HuMAb mice; Medarex
      Inc.) with soluble E2 envelope glycoprotein derived from a genotype 1a virus
      (H77). Two HuMAbs, HCV1 and 95-2, were selected for further study based on
      initial cross-reactivity with soluble E2 glycoproteins derived from genotypes 1a
      and 1b, as well as neutralization of lentivirus pseudotyped with HCV 1a and 1b
      envelope glycoproteins. Additionally, HuMAbs HCV1 and 95-2 potently neutralized
      pseudoviruses from all genotypes tested (1a, 1b, 2b, 3a, and 4a). Epitope mapping
      with mammalian and bacterially expressed proteins, as well as synthetic peptides,
      revealed that HuMAbs HCV1 and 95-2 recognize a highly conserved linear epitope
      spanning amino acids 412 to 423 of the E2 glycoprotein. The capacity to recognize
      and neutralize a broad range of genotypes, the highly conserved E2 epitope, and
      the fully human nature of the antibodies make HuMAbs HCV1 and 95-2 excellent
      candidates for treatment of HCV-positive individuals undergoing liver
      transplantation.

PMID- 19759152
TI  - Loss of raltegravir susceptibility by human immunodeficiency virus type 1 is
      conferred via multiple nonoverlapping genetic pathways.
AB  - The human immunodeficiency virus type 1 (HIV-1) integrase mutations N155H and
      Q148R(H)(K) that reduce susceptibility to the integrase inhibitor raltegravir
      have been identified in patients failing treatment regimens containing
      raltegravir. Whether these resistance mutations occur individually or in
      combination within a single virus genome has not been defined, nor do we fully
      understand the impact of these primary mutations and other secondary mutations on
      raltegravir susceptibility and viral replication capacity. To address these
      important questions, we investigated the raltegravir susceptibility and
      replication capacity of viruses containing mutations at positions 155 and 148
      separately or in combination with secondary mutations selected in subjects
      failing treatment regimens containing raltegravir. Clonal analysis demonstrated
      that N155H and Q148R(H)(K) occur independently, not in combination. Viruses
      containing a Q148R(H)(K) mutation generally displayed larger reductions in
      raltegravir susceptibility than viruses with an N155H mutation. Analysis of site
      directed mutants indicated that E92Q in combination with N155H resulted in a
      higher level of resistance to raltegravir than N155H alone. Viruses containing a
      Q148R(H) mutation together with a G140S mutation were more resistant to
      raltegravir than viruses containing a Q148R(H) mutation alone; however, viruses
      containing G140S and Q148K were more susceptible to raltegravir than viruses
      containing a Q148K mutation alone. Both N155H and Q148R(H)(K) mutations reduced
      the replication capacity, while the addition of secondary mutations either
      improved or reduced the replication capacity depending on the primary mutation.
      This study demonstrates distinct genetic pathways to resistance in subjects
      failing raltegravir regimens and defines the effects of primary and secondary
      resistance mutations on raltegravir susceptibility and replication capacity.

PMID- 19759153
TI  - Origin and phylodynamics of rabbit hemorrhagic disease virus.
AB  - To determine the origin, phylogenetic relationships, and evolutionary dynamics of
      rabbit hemorrhagic disease virus (RHDV), we examined 210 partial and complete
      capsid gene nucleotide sequences. Using a Bayesian Markov chain Monte Carlo
      approach, we estimated that these sequences evolved at a rate of 3.9 x 10(-4) to
      11.9 x 10(-4) nucleotide substitutions per site per year. This rate was
      consistent across subsets of data, was robust in response to recombination, and
      casts doubt on the provenance of viral strains isolated from the 1950s to the
      1970s, which share strong sequence similarity to modern isolates. Using the same
      analysis, we inferred that the time to the most recent common ancestor for a
      joint group of RHDV and rabbit calicivirus sequences was <550 years ago and was
      <150 years ago for the RHDV isolates that have spread around the world since
      1984. Importantly, multiple lineages of RHDV were clearly circulating before the
      major Chinese outbreak of 1984, a finding indicative of an early evolution of
      RHDV virulence. Four phylogenetic groups within RHDV were defined and analyzed
      separately. Each group shared a common ancestor in the mid-1960s or earlier, and
      each showed an expansion of populations starting before 1984. Notably, the group
      characterized by the antigenic variant RHDVa harbors the greatest genetic
      diversity, compatible with an elevated fitness. Overall, we contend that the high
      virulence of RHDV likely evolved once in the early part of the 20th century, well
      before the documented emergence of rabbit hemorrhagic disease in 1984.

PMID- 19759154
TI  - Reticuloendotheliosis virus strain T induces miR-155, which targets JARID2 and
      promotes cell survival.
AB  - The oncogenic microRNA miR-155 is upregulated by several oncogenic viruses. The
      precursor of miR-155, termed bic, was first observed to cooperate with myc in
      chicken B-cell lymphomas induced by avian leukosis proviral integrations. We
      identified another oncogenic retrovirus, reticuloendotheliosis virus strain T
      (REV-T), that upregulates miR-155 in chicken embryo fibroblasts. We also observed
      very high levels of miR-155 in REV-T-induced B-cell lymphomas. To study the role
      of miR-155 in these tumors, we identified JARID2/Jumonji, a cell cycle regulator
      and part of a histone methyltransferase complex, as a target of miR-155. The
      overexpression of miR-155 decreased levels of endogenous JARID2 mRNA. We
      confirmed that miR-155 directly targets both human and chicken JARID2 by assaying
      the repression of reporters containing the JARID2 3'-untranslated regions.
      Further, the overexpression of a sponge complementary to miR-155 in a tumor cell
      line increased endogenous JARID2 mRNA levels. The overexpression of JARID2 in
      chicken fibroblasts led to decreased cell numbers and an increase in apoptotic
      cells. The overexpression of miR-155 rescued cells undergoing cytopathic effect
      caused by infection with subgroup B avian retroviruses. Therefore, we propose
      that miR-155 has a prosurvival function that is mediated through the
      downregulation of targets including JARID2.

PMID- 19759155
TI  - Adeno-associated virus site-specific integration is mediated by proteins of the
      nonhomologous end-joining pathway.
AB  - Adeno-associated virus type 2 (AAV 2) is the only eukaryotic virus capable of
      site-specific integration; the target site is at chromosome 19q13.4, a site
      termed AAVS1. The biology of AAV latency has been extensively studied in cell
      culture, yet the precise mechanism and the required cellular factors are not
      known. In this study, we assessed the relative frequencies of stable site
      specific integration by characterization of cell clones containing integrated AAV
      vectors. By this assay, two proteins involved in nonhomologous end joining
      (NHEJ), DNAPKcs and ligase IV, exhibit differential effects on AAV site-specific
      integration. DNAPKcs is not required; its presence increases the frequency of
      junction formation indicative of site-specific integration, but seems to reduce
      the ratio of site-specific integration to random integration (i.e., the latter is
      even more enhanced). In contrast, site-specific integration is significantly
      reduced relative to random integration in cells deficient in ligase IV
      expression. Furthermore, we show that single-stranded AAV vectors are better
      substrates for site-specific integration than are self-complementary AAV vectors;
      the absence of DNAPKcs did not affect the targeted integration of these double
      stranded AAV vectors. Together, these data suggest that NHEJ proteins participate
      in site-specific integration, and indicate a role for the single-stranded form of
      AAV DNA in targeted integration.

PMID- 19759156
TI  - The z protein of the new world arenavirus tacaribe virus has bona fide budding
      activity that does not depend on known late domain motifs.
AB  - The arenavirus small RING finger Z protein has been shown to be the main driving
      force of budding for several arenaviruses. This Z budding activity was found to
      be mediated by the late (L)-domain motifs P(T/S)AP and PPXY, located at the C
      terminus of Z. Here, we show that the Z protein of Tacaribe virus (TACV), a New
      World arenavirus, buds efficiently from cells despite lacking the canonical L
      domain motifs P(T/S)AP and PPXY. Likewise, potential L-domain motifs ASAP and
      YLCL present in TACV Z did not exhibit any significant contribution to TACV Z
      budding activity. Budding of TACV Z was Tsg101 independent but required the
      activity of Vps4A/B. These results indicate that TACV Z utilizes a budding
      mechanism distinct from that reported for other arenaviruses.

PMID- 19759157
TI  - The crystal structure of PF-8, the DNA polymerase accessory subunit from Kaposi's
      sarcoma-associated herpesvirus.
AB  - Kaposi's sarcoma-associated herpesvirus is an emerging pathogen whose mechanism
      of replication is poorly understood. PF-8, the presumed processivity factor of
      Kaposi's sarcoma-associated herpesvirus DNA polymerase, acts in combination with
      the catalytic subunit, Pol-8, to synthesize viral DNA. We have solved the crystal
      structure of residues 1 to 304 of PF-8 at a resolution of 2.8 A. This structure
      reveals that each monomer of PF-8 shares a fold common to processivity factors.
      Like human cytomegalovirus UL44, PF-8 forms a head-to-head dimer in the form of a
      C clamp, with its concave face containing a number of basic residues that are
      predicted to be important for DNA binding. However, there are several differences
      with related proteins, especially in loops that extend from each monomer into the
      center of the C clamp and in the loops that connect the two subdomains of each
      protein, which may be important for determining PF-8's mode of binding to DNA and
      to Pol-8. Using the crystal structures of PF-8, the herpes simplex virus
      catalytic subunit, and RB69 bacteriophage DNA polymerase in complex with DNA and
      initial experiments testing the effects of inhibition of PF-8-stimulated DNA
      synthesis by peptides derived from Pol-8, we suggest a model for how PF-8 might
      form a ternary complex with Pol-8 and DNA. The structure and the model suggest
      interesting similarities and differences in how PF-8 functions relative to
      structurally similar proteins.

PMID- 19759158
TI  - Mutations in the thumb allow human immunodeficiency virus type 1 reverse
      transcriptase to be cleaved by protease in virions.
AB  - Although human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT)
      has been extensively studied, there are still significant questions about the
      effects of mutations on the maturation and stability of RT. We show here that a
      significant fraction (>80%) of the single point mutations we generated in the
      thumb subdomain of HIV-1 (RT) affect the stability of RT in virions. Fragments of
      the unstable mutant RTs can be detected in Western blots of virion proteins;
      however, the degree of degradation varies. The titers of the mutants whose
      virions contain degraded RTs are reduced. Some, but not all, of the unstable RT
      thumb subdomain mutants we analyzed have a temperature-sensitive phenotype. A
      preliminary survey of mutations in other subdomains of RT shows that some of
      these mutations also destabilize RT. The stability of the RT mutants is enhanced
      by the addition of a protease inhibitor, suggesting that the viral protease plays
      an important role in the degradation of the mutant RTs. These results confirm and
      extend earlier reports of mutations that affect the stability of RT in virions.
      The data suggest that the stability of a mutant RT in virions could be a major
      factor in determining the virus titer and, by extension, viral fitness, which
      could affect whether a mutation in RT is acceptable to the virus.

PMID- 19759159
TI  - The pre-S1 and antigenic loop infectivity determinants of the hepatitis B virus
      envelope proteins are functionally independent.
AB  - The hepatitis B virus (HBV) envelope proteins bear two determinants of viral
      entry: a receptor-binding site (RBS) in the pre-S1 domain of the large envelope
      protein and a conformation-dependent determinant, of unknown function, in the
      antigenic loop (AGL) of the small, middle, and large envelope proteins. Using an
      in vitro infection assay consisting of susceptible HepaRG cells and the hepatitis
      delta virus (HDV) as a surrogate of HBV, we first investigated whether
      subelements of the pre-S1 determinant (amino acids 2 to 75), i.e., the N-terminal
      myristoyl anchor, subdomain 2-48 (RBS), and subdomain 49-75, were functionally
      separable. In transcomplementation experiments, coexpression of two distinct
      infectivity-deficient pre-S1 mutants at the surface of HDV virions failed to
      restore infectivity, indicating that the myristoyl anchor, the 2-48 RBS, and the
      49-75 sequence, likely cooperate in cis at viral entry. Furthermore, we showed
      that as much as 52% of total pre-S1 in the HDV envelope could bear infectivity
      deficient lesions without affecting entry, indicating that a small number of pre
      S1 polypeptides-estimated at three to four per virion-is sufficient for
      infectivity. We next investigated the AGL activity in the small or large envelope
      protein background (S- and L-AGL, respectively) and found that lesions in S-AGL
      were more deleterious to infectivity than in L-AGL, a difference that reflects
      the relative stoichiometry of the small and large envelope proteins in the viral
      envelope. Finally, we showed that C147S, an AGL infectivity-deficient
      substitution, exerted a dominant-negative effect on infectivity, likely
      reflecting an involvement of C147 in intermolecular disulfide bonds.

PMID- 19759160
TI  - The Nedd4-type Rsp5p ubiquitin ligase inhibits tombusvirus replication by
      regulating degradation of the p92 replication protein and decreasing the activity
      of the tombusvirus replicase.
AB  - Recent in vitro proteomics screens revealed that many host proteins could
      interact with the replication proteins of Tomato bushy stunt virus (TBSV), which
      is a small, plus-stranded RNA virus (Z. Li, D. Barajas, T. Panavas, D. A. Herbst,
      and P. D. Nagy, J. Virol. 82:6911-6926, 2008). To further our understanding of
      the roles of host factors in TBSV replication, we have tested the effect of
      Rsp5p, which is a member of the Nedd4 family of E3 ubiquitin ligases. The full
      length Rsp5p, via its WW domain, is shown to interact with p33 and the central
      portion of p92(pol) replication proteins. We find that overexpression of Rsp5p
      inhibits TBSV replication in Saccharomyces cerevisiae yeast, while downregulation
      of Rsp5p leads to increased TBSV accumulation. The inhibition is caused by Rsp5p
      guided degradation of p92(pol), while the negative effect on the p33 level is
      less pronounced. Interestingly, recombinant Rsp5p also inhibits TBSV RNA
      replication in a cell-free replication assay, likely due to its ability to bind
      to p33 and p92(pol). We show that the WW domain of Rsp5p, which is involved in
      protein interactions, is responsible for inhibition of TBSV replication, whereas
      the HECT domain, involved in protein ubiquitination, is not necessary for Rsp5p
      mediated inhibition of viral replication. Overall, our data suggest that direct
      binding between Rsp5p and p92(pol) reduces the stability of p92(pol), with
      consequent inhibition of TBSV replicase activity.

PMID- 19759161
TI  - Phosphorylation of the nuclear form of varicella-zoster virus immediate-early
      protein 63 by casein kinase II at serine 186.
AB  - Varicella-zoster virus (VZV) open reading frame (ORF) 63 is abundantly
      transcribed in latently infected human ganglia and encodes a 278-amino-acid
      protein, IE63, with immediate-early kinetics. IE63 is expressed in the cytoplasm
      of neurons during VZV latency and in both the cytoplasm and the nucleus during
      productive infection; however, the mechanism(s) involved in IE63 nuclear import
      and retention has remained unclear. We constructed and identified a recombinant
      monoclonal antibody to detect a posttranslationally modified form of IE63.
      Analysis of a series of IE63 truncation and substitution mutants showed that
      amino acids 186 to 195 are required for antibody binding. Synthetic peptides
      corresponding to this region identified IE63 S186 as a target for casein kinase
      II phosphorylation. In addition, acidic charges supplied by E194 and E195 were
      required for antibody binding. Immunofluorescence analysis of VZV-infected MeWo
      cells using the recombinant monoclonal antibody detected IE63 exclusively in the
      nuclei of infected cells, indicating that casein kinase II phosphorylation of
      S186 occurs in the nucleus and possibly identifying an initial molecular event
      operative in VZV reactivation.

PMID- 19759162
TI  - Multifaceted sequence-dependent and -independent roles for reovirus FAST protein
      cytoplasmic tails in fusion pore formation and syncytiogenesis.
AB  - Fusogenic reoviruses utilize the FAST proteins, a novel family of nonstructural
      viral membrane fusion proteins, to induce cell-cell fusion and syncytium
      formation. Unlike the paradigmatic enveloped virus fusion proteins, the FAST
      proteins position the majority of their mass within and internal to the membrane
      in which they reside, resulting in extended C-terminal cytoplasmic tails (CTs).
      Using tail truncations, we demonstrate that the last 8 residues of the 36-residue
      CT of the avian reovirus p10 FAST protein and the last 20 residues of the 68
      residue CT of the reptilian reovirus p14 FAST protein enhance, but are not
      required for, pore expansion and syncytium formation. Further truncations
      indicate that the membrane-distal 12 residues of the p10 and 47 residues of the
      p14 CTs are essential for pore formation and that a residual tail of 21 to 24
      residues that includes a conserved, membrane-proximal polybasic region present in
      all FAST proteins is insufficient to maintain FAST protein fusion activity.
      Unexpectedly, a reextension of the tail-truncated, nonfusogenic p10 and p14
      constructs with scrambled versions of the deleted sequences restored pore
      formation and syncytiogenesis, while reextensions with heterologous sequences
      partially restored pore formation but failed to rescue syncytiogenesis. The
      membrane-distal regions of the FAST protein CTs therefore exert multiple effects
      on the membrane fusion reaction, serving in both sequence-dependent and sequence
      independent manners as positive effectors of pore formation, pore expansion, and
      syncytiogenesis.

PMID- 19759163
TI  - Impacts on work absence and performance: what really matters?
AB  - BACKGROUND: A number of factors influence an individual's decision to take
      sickness absence or to remain at work while ill. The relationship between health,
      work characteristics, individual perceptions of work and sickness absence and
      performance is complex and further clarification of the interactions between
      these factors is necessary. AIMS: To assess the relative impact of health, work
      characteristics and perceptions of work on absence and performance. METHODS:
      Cross-sectional survey of two public sector organizations (n = 505). Data were
      analysed using multivariate linear regression to assess the individual and
      combined influence of each class of independent variables on the following: days
      sickness absence, spells of sickness absence, VAS performance and presenteeism.
      RESULTS: Characteristics of work were weakly associated with days absence and
      performance. Perceptions of work were more strongly associated with performance
      than absence. Measures of mental health, rather than physical health, had the
      greatest influence on ability to work. Poor health had a greater impact on work
      performance than work absence. When considered together, health variables
      accounted for the largest proportion of explained variance in both absence and
      performance when compared with characteristics of work and work perceptions.
      CONCLUSIONS: Using absence as a marker of health-associated compromise at work
      may lead to an underestimation of the impact of health on work. This study
      demonstrates the need to manage the impact of health problems on the workforce
      not only from a bio-medical perspective but also in terms of the psychological
      pressures and the social context in which employees work.

PMID- 19759164
TI  - Pregnancy outcomes related to gestational weight gain in women defined by their
      body mass index, parity, height, and smoking status.
AB  - BACKGROUND: Recommendations for gestational weight gain (GWG) account for a
      woman's prepregnancy body mass index (BMI), but other factors may be important.
      OBJECTIVES: The objectives were to investigate whether, within BMI categories,
      the GWG with the lowest risks to mother and infant varied with parity and to
      describe these risks in short (<160 cm), young (<20 y), and smoking women.
      DESIGN: Of 27,030 primiparous and 31,407 multiparous women with term births
      within the Danish National Birth Cohort, self-reported GWG was divided into 6
      categories (<5, 5-9, 10-15, 16-19, 20-24, and > or =25 kg). Population-based
      registers provided information about birth outcomes. GWG-specific absolute
      adjusted risks for emergency cesarean delivery, birth of a small-for-gestational
      age (SGA) or large-for-gestational-age (LGA) infant, and postpartum (6 mo) weight
      retention (PPWR) were compared across different types of women. RESULTS: The risk
      of SGA decreased with increasing GWG in both parity groups, but SGA risk <10% was
      reached at 2-3 GWG categories lower in multiparae than in primiparae. An excess
      risk of LGA was present only in obese primiparae and multiparae, but the PPWR
      risk increased with increasing GWG irrespective of BMI and parity. Young
      primiparae had better outcomes than other primiparae. Short women had a higher
      risk of emergency cesarean delivery that varied minimally with GWG. Smokers had a
      higher SGA risk and had a PPWR risk similar to that of nonsmokers. CONCLUSIONS:
      The tradeoff in risk between mother and infant is reached at lower GWG in
      multiparae than in primiparae; therefore, a lower GWG may be needed among
      multiparae. Differential guidelines seem unnecessary for short or young women or
      smokers.

PMID- 19759165
TI  - Alcohol consumption is associated with high concentrations of urinary
      hydroxytyrosol.
AB  - BACKGROUND: Previously, we reported the presence of hydroxytyrosol in red wine
      and higher human urinary recovery of total hydroxytyrosol than that expected
      after a single red wine intake. We hypothesized that the alcohol present in wine
      could promote endogenous hydroxytyrosol generation. OBJECTIVE: The objective was
      to assess the relation between alcohol consumption and urinary hydroxytyrosol
      concentrations. DESIGN: This was a cross-sectional study with baseline data from
      a subsample of the PREvencion con DIeta MEDiterranea (PREDIMED) trial, an
      intervention study directed at testing the efficacy of the Mediterranean diet on
      the primary prevention of cardiovascular disease. Participants included 1045
      subjects, aged 55-80 y, who were at high cardiovascular risk. Alcohol consumption
      was estimated through a validated food-frequency questionnaire. Urinary
      hydroxytyrosol and ethyl glucuronide, a biomarker of alcohol consumption, were
      measured. RESULTS: Urinary ethyl glucuronide concentrations were directly related
      to alcohol and wine consumption (P < 0.001) as well as to urinary hydroxytyrosol
      in both sexes (P < 0.001). The degree of alcohol consumption was directly
      associated with urinary hydroxytyrosol in male alcohol consumers (P < 0.001).
      Multivariate logistic regression analyses showed a significant linear trend (P <
      0.05) for elevated hydroxytyrosol concentrations with an increase in alcohol
      consumption. Intakes of >20 g (2 drinks)/d and >10 g (1 drink)/d alcohol in men
      and women, respectively, were associated (P < 0.05) with elevated concentrations
      of hydroxytyrosol. CONCLUSIONS: We report for the first time a direct association
      between urinary hydroxytyrosol and alcohol consumption at a population level.
      These findings reinforce previous work in human and animal models that examines
      wine as a source of hydroxytyrosol and alcohol as an indirect promoter of
      endogenous hydroxytyrosol generation. This trial was registered at controlled
      trials.com/isrctn/ as ISRCTN 35739639.

PMID- 19759166
TI  - Soy isoflavone supplementation and bone mineral density in menopausal women: a 2
      y multicenter clinical trial.
AB  - BACKGROUND: Isoflavones are naturally occurring plant estrogens that are abundant
      in soy. Although purported to protect against bone loss, the efficacy of soy
      isoflavone supplementation in the prevention of osteoporosis in postmenopausal
      women remains controversial. OBJECTIVE: Our aim was to test the effect of soy
      isoflavone supplementation 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 of soy hypocotyl aglycone isoflavones
      plus calcium and vitamin D on bone changes in 403 postmenopausal women. Study
      subjects were tested annually and changes in whole-body and regional bone mineral
      density (BMD), bone mineral content (BMC), and T scores were assessed. Changes in
      serum biochemical markers of bone metabolism were also assessed. RESULTS: After
      study site, soy intake, and pretreatment values were controlled for, subjects
      receiving a daily supplement with 120 mg soy isoflavones had a statistically
      significant smaller reduction in whole-body BMD than did the placebo group both
      at 1 y (P < 0.03) and at 2 y (P < 0.05) of treatment. Smaller decreases in whole
      body BMD T score were observed among this group of women at 1 y (P < 0.03) but
      not at 2 y of treatment. When compared with the placebo, soy isoflavone
      supplementation had no effect on changes in regional BMD, BMC, T scores, or
      biochemical markers of bone metabolism. CONCLUSION: Daily supplementation with
      120 mg soy hypocotyl isoflavones reduces whole-body bone loss but does not slow
      bone loss at common fracture sites in healthy postmenopausal women. This trial
      was registered at clinicaltrials.gov as NCT00665860.

PMID- 19759167
TI  - Plasma pharmacokinetics of alkylresorcinol metabolites: new candidate biomarkers
      for whole-grain rye and wheat intake.
AB  - BACKGROUND: Alkylresorcinols are phenolic compounds that are present almost
      exclusively in rye and wheat fiber. Alkylresorcinols are absorbed and thereafter
      metabolized to 3,5-dihydroxybenzoic acid (DHBA) and 3-(3,5-dihydroxyphenyl)-1
      propanoic acid (DHPPA), which have been detected in human urine and plasma.
      OBJECTIVE: The objective was to determine the plasma pharmacokinetics of DHBA and
      DHPPA in human subjects to estimate whether they show potential as biomarkers for
      whole-grain rye and/or wheat intake. DESIGN: Fifteen human volunteers followed a
      low-alkylresorcinol diet for 2 d before ingesting a single dose of high-fiber rye
      bread containing 100 mg alkylresorcinols [corrected]. Plasma samples were
      collected for 25 h, and the alkylresorcinol metabolites were quantified by HPLC
      with coulometric electrode array detection. RESULTS: Maximum concentrations were
      reached at approximately 6 h for both metabolites, although interindividual
      variation was found. The half-life was significantly (P < 0.0002) longer for
      DHPPA (16.3 h) than for DHBA (10.1 h). No significant differences were discovered
      between women and men in the half-life of each metabolite, which, from a
      pharmacokinetic point of view, is the most important parameter. The area under
      the curve differed significantly between DHBA and DHPPA (P < 0.0001) and between
      women and men (P = 0.03 for DHBA and P = 0.01 for DHPPA). However, when corrected
      for body weight, the difference between sexes was no longer significant.
      CONCLUSIONS: Our results suggest that DHBA and DHPPA are both good candidate
      biomarkers for whole-grain rye and/or wheat intake; however, DHPPA is the better
      indicator because of its longer half-life. This could provide a practical tool
      when investigating the association between diet and diseases.

PMID- 19759168
TI  - Low serum folate and vitamin B-6 are associated with an altered cancellous bone
      structure in humans.
AB  - BACKGROUND: Several clinical trials have reported B vitamins to be associated
      with osteoporosis. OBJECTIVE: Our objective was to investigate whether low serum
      B vitamins are associated with altered structural and biomechanical properties of
      human bone. DESIGN: Femoral heads of 94 men and women who underwent hip
      arthroplasty were analyzed by using dual-energy X-ray absorptiometry (DXA),
      biomechanical testing (indentation method), and histomorphometry. In addition,
      blood was collected to measure serum concentrations of homocysteine, folate,
      vitamin B-6, vitamin B-12, the bone formation marker osteocalcin, and the bone
      resorption marker tartrate-resistant acid phosphatase (TRAP). Measurement
      outcomes were grouped according to subjects with high and low serum
      concentrations, respectively, of folate, vitamin B-6, and vitamin B-12 (n = 47
      for each group). RESULTS: Histomorphometric analysis showed a significantly lower
      trabecular thickness and trabecular area in subjects with low serum folate
      concentrations than in those with high serum folate concentrations and a
      significantly lower trabecular number in subjects with low serum vitamin B-6
      concentrations than in those with high serum vitamin B-6 concentrations. In
      contrast, we found a comparable trabecular structure in subjects with high and
      low serum vitamin B-12 concentrations. DXA and biomechanical testing did not show
      significant differences between subjects with high and low serum B vitamin
      concentrations. Osteocalcin was significantly lowered in subjects with a low
      serum B vitamin concentration, whereas there was no association between serum B
      vitamins and TRAP. CONCLUSION: The results of the present study indicate that low
      serum folate and vitamin B-6 concentrations, but not low serum vitamin B-12
      concentrations, are associated with an altered morphology of human bone.

PMID- 19759169
TI  - Increased breast cancer risk at high plasma folate concentrations among women
      with the MTHFR 677T allele.
AB  - BACKGROUND: Folate is involved in DNA synthesis and methylation and may thereby
      influence carcinogenesis. OBJECTIVES: We examined plasma folate (P-folate)
      concentration in relation to genotypes of the folate-metabolizing enzyme
      methylenetetrahydrofolate reductase [MTHFR 677C-->T (rs1801133) and 1298A-->C
      (rs1801131)]. We also explored whether P-folate was associated with risk of
      postmenopausal breast cancer overall and in subgroups with genetic variants of
      the MTHFR single nucleotide polymorphisms (SNPs). DESIGN: This nested case
      control study included 313 cases (age 55-73 y at baseline) with invasive breast
      cancer and 626 control subjects, matched on age and blood-sample date, from the
      population-based Malmo Diet and Cancer cohort. P-folate and MTHFR genotypes were
      determined for 310 cases and 611 controls. P-folate according to genotype was
      calculated by using analysis of variance. Odds ratios were obtained by using
      logistic regression. All tests were 2-sided. RESULTS: The variant 677T allele was
      associated with lower P-folate. In women with the 677T allele, a high P-folate
      concentration was associated with increased breast cancer risk (P for trend
      across P-folate tertiles = 0.03). Interaction was seen between the 677C-->T SNP
      and P-folate (P = 0.002). A positive association, which was seen between P-folate
      and breast cancer risk in 1298AA women (P = 0.01), was probably due to linkage
      between the 2 SNPs. Overall, and in women with other genotypes, no significant
      associations were observed. CONCLUSIONS: Our results suggest an association of
      high P-folate concentration with increased risk of postmenopausal breast cancer
      in carriers of the 677T allele. The findings underline the importance of genetic
      variation of MTHFR in the complex relation between folate and cancer.

PMID- 19759170
TI  - Consumption of 2 and 4 egg yolks/d for 5 wk increases macular pigment
      concentrations in older adults with low macular pigment taking cholesterol
      lowering statins.
AB  - BACKGROUND: Lutein and zeaxanthin may reduce the risk of dry, age-related macular
      degeneration because of their photo-oxidative role as macular pigment. OBJECTIVE:
      The present study evaluated serum lutein, zeaxanthin, and macular pigment optical
      density (MPOD) responses at 0.25 degrees , 0.5 degrees , and 1 degree retinal
      eccentricities to the consumption of 2 and 4 egg yolks/d by older adults taking
      cholesterol-lowering medications. DESIGN: Subjects consumed foods containing 2
      followed by 4 egg yolks/d for 5 wk each with a 4-wk egg-free period at baseline
      and between the 2 interventions. RESULTS: Changes in MPOD (n = 37) with egg yolk
      consumption were inversely associated (P < 0.05) with baseline MPOD. Subjects
      with low-baseline MPOD (defined as MPOD < or =0.5 at 0.25 degrees , < or =0.4 at
      0.5 degrees , and < or =0.35 at 1 degrees ) showed increases of < or =50% (P <
      0.05) with 4 egg yolks at the 3 retinal eccentricities. MPOD increased by 31% (P
      = 0.059) at 0.5 degrees with 2 egg yolks. Serum lutein increased by only 16% and
      24% (P < 0.05) compared with increases of 36% and 82% (P < 0.001) in serum
      zeaxanthin (n = 52) after consumption of 2 and 4 egg yolks, respectively. Serum
      HDL cholesterol increased by 5% (P < 0.05) after consumption of 2 and 4 egg
      yolks. Serum LDL cholesterol did not change with either egg yolk treatment.
      CONCLUSIONS: Consumption of 4 egg yolks/d, and possibly of 2 egg yolks/d, for 5
      wk benefited macular health in older adults with low MPOD. Serum HDL cholesterol
      increased without an increase in LDL cholesterol in this study population, most
      of whom were taking cholesterol-lowering statins.

PMID- 19759171
TI  - Perinatal risk factors for childhood obesity and metabolic dysregulation.
AB  - BACKGROUND: Childhood obesity has increased significantly in recent decades.
      OBJECTIVE: The objective was to examine the perinatal risk factors related to
      childhood obesity. DESIGN: In a prospective study, 89 women with normal glucose
      tolerance (NGT) or gestational diabetes mellitus (GDM) and their offspring were
      evaluated at birth and at 8.8 +/- 1.8 y. At birth, obstetrical data, parental
      anthropometric measures, and neonatal body composition were assessed; at follow
      up, diet and activity were assessed and laboratory studies were conducted. Weight
      was classified by using weight for age and sex, and body composition was measured
      by using dual-energy X-ray absorptiometry. In childhood, data were analyzed as
      tertiles and prediction models were developed by using logistic and stepwise
      regression. RESULTS: No significant differences in Centers for Disease Control
      and Prevention weight percentiles, body composition, and most metabolic measures
      were observed between children of mothers with NGT and GDM at follow-up. Children
      in the upper tertile for weight had greater energy intake (P = 0.02), skinfold
      thickness (P = 0.0001), and leptin concentrations (P < 0.0001) than did those in
      tertiles 1 and 2. Children in the upper tertile for percentage body fat had
      greater waist circumference (P = 0.0001), insulin resistance (P = 0.002), and
      triglyceride (P = 0.009) and leptin (P = 0.0001) concentrations than did children
      in tertiles 1 and 2. The correlation between body fat at birth and follow-up was
      r = 0.29 (P = 0.02). The strongest perinatal predictor for a child in the upper
      tertile for weight was maternal pregravid body mass index (BMI; kg/m(2)) >30
      (odds ratio: 3.75; 95% CI: 1.39, 10.10; P = 0.009) and for percentage body fat
      was maternal pregravid BMI >30 (odds ratio: 5.45; 95% CI: 1.62, 18.41; P =
      0.006). CONCLUSION: Maternal pregravid BMI, independent of maternal glucose
      status or birth weight, was the strongest predictor of childhood obesity.

PMID- 19759172
TI  - Characterization and assessment of dermal and inhalable nickel exposures in
      nickel production and primary user industries.
AB  - The aim of this study was to measure the levels of nickel in the skin contaminant
      layer of workers involved in specific processes and tasks within the primary
      nickel production and primary nickel user industries. Dermal exposure samples
      were collected using moist wipes to recover surface contamination from defined
      areas of skin. These were analysed for soluble and insoluble nickel species.
      Personal samples of inhalable dust were also collected to determine the
      corresponding inhalable nickel exposures. The air samples were analysed for total
      inhalable dust and then for soluble, sulfidic, metallic, and oxidic nickel
      species. The workplace surveys were carried out in five different workplaces,
      including three nickel refineries, a stainless steel plant, and a powder
      metallurgy plant, all of which were located in Europe. Nickel refinery workers
      involved with electrolytic nickel recovery processes had soluble dermal nickel
      exposure of 0.34 microg cm(-2) [geometric mean (GM)] to the hands and forearms.
      The GM of soluble dermal nickel exposure for workers involved in packing nickel
      salts (nickel chloride hexahydrate, nickel sulphate hexahydrate, and nickel
      hydroxycarbonate) was 0.61 microg cm(-2). Refinery workers involved in packing
      nickel metal powders and end-user powder operatives in magnet production had the
      highest dermal exposure (GM = 2.59 microg cm(-2) soluble nickel). The hands,
      forearms, face, and neck of these workers all received greater dermal nickel
      exposure compared with the other jobs included in this study. The soluble nickel
      dermal exposures for stainless steel production workers were at or slightly above
      the limit of detection (0.02 microg cm(-2) soluble nickel). The highest inhalable
      nickel concentrations were observed for the workers involved in nickel powder
      packing (GM = 0.77 mg m(-3)), although the soluble component comprised only 2% of
      the total nickel content. The highest airborne soluble nickel exposures were
      associated with refineries using electrolytic processes for nickel recovery (GM =
      0.04 mg m(-3) total nickel, containing 82% soluble nickel) and those jobs
      involving contact with soluble nickel compounds (GM = 0.02 mg m(-3) total nickel
      content, containing 76% soluble nickel). The stainless steel workers were exposed
      to low concentrations of relatively insoluble airborne nickel species (GM = 0.03
      mg m(-3) total nickel, containing 1% soluble nickel). A statistically significant
      correlation was observed between dermal exposures for all anatomical areas across
      all tasks. In addition, the dermal and inhalable (total) nickel exposures were
      similarly associated. Overall, dermal exposures to nickel, nickel compounds, and
      nickel alloys were relatively low. However, exposures were highly variable, which
      can be explained by the inconsistent use of personal protective equipment,
      varying working practices, and different standards of automation and engineering
      controls within each exposure category.

PMID- 19759173
TI  - Exposure to polycyclic aromatic hydrocarbons (PAHs), mutagenic aldehydes, and
      particulate matter in Norwegian a la carte restaurants.
AB  - OBJECTIVES: The aim of the study was to characterize the exposure regarding
      polycyclic aromatic hydrocarbons (PAHs) and higher mutagenic aldehydes in the
      breathing zone of the cook during work in Norwegian a la carte restaurants.
      Levels of particle exposure were also measured to make the results comparable to
      other studies. METHODS: Personal measurements of the levels of PAHs, higher
      aldehydes, and total particles were performed in three restaurants in the city of
      Trondheim in the middle of Norway. RESULTS: Naphthalene was detected within the
      range of 0.05-0.27 microg m(-3) air, and the total mean value for all three
      restaurants was 0.18 microg m(-3) air. The measured levels of mutagenic aldehydes
      were between 1.03 and 17.67 microg m(-3) air. The mean mass concentration of
      total particles measured in the three restaurants was 1.93 mg m(-3), and the
      levels registered were within the range 0.32-7.51 mg m(-3). CONCLUSIONS: Working
      as a cook in a Norwegian a la carte restaurant with some manual panfrying
      involves exposure to components in cooking fumes which may cause adverse health
      effects. Additional studies are necessary in order to identify relations between
      exposure levels and the adverse health effects of cooking fumes.

PMID- 19759174
TI  - Paternal DNA packaging in spermatozoa: more than the sum of its parts? DNA,
      histones, protamines and epigenetics.
AB  - Haploid male germ cells package their DNA into a volume that is typically 10% or
      less that of a somatic cell nucleus. To achieve this remarkable level of
      compaction, spermatozoa replace most of their histones with smaller, highly basic
      arginine and (in eutherians) cysteine rich protamines. One reason for such a high
      level of compaction is that it may help optimise nuclear shape and hence support
      the gametes' swimming ability for the long journey across the female reproductive
      tract to the oocyte. Super-compaction of the genome may confer additional
      protection from the effects of genotoxic factors. However, many species including
      the human retain a fraction of their chromatin in the more relaxed nucleosomal
      configuration that appears to run counter to the ergonomic, toroidal and
      repackaging of sperm DNA. Recent research suggests that the composition of this
      'residual' nucleosomal compartment, a generally overlooked feature of the male
      gamete, is far more significant and important than previously thought. In this
      respect, the transport and incorporation of modified paternal histones by the
      spermatozoon to the zygote has been demonstrated and indicates another potential
      paternal effect in the epigenetic reprogramming of the zygote following
      fertilisation that is independent of imprinting status. In this review, the most
      recent research into mammalian spermatozoal chromatin composition is discussed
      alongside evidence for conserved, non-randomly located nucleosomal domains in
      spermatozoal nuclei, all supporting the hypothesis that the spermatozoon delivers
      a novel epigenetic signature to the egg that may be crucial for normal
      development. We also provide some thoughts on why this signature may be required
      in early embryogenesis.

PMID- 19759175
TI  - Streamlined architecture and glycosylphosphatidylinositol-dependent trafficking
      in the early secretory pathway of African trypanosomes.
AB  - The variant surface glycoprotein (VSG) of bloodstream form Trypanosoma brucei
      (Tb) is a critical virulence factor. The VSG glycosylphosphatidylinositol (GPI)
      anchor strongly influences passage through the early secretory pathway. Using a
      dominant-negative mutation of TbSar1, we show that endoplasmic reticulum (ER)
      exit of secretory cargo in trypanosomes is dependent on the coat protein complex
      II (COPII) machinery. Trypanosomes have two orthologues each of the Sec23 and
      Sec24 COPII subunits, which form specific heterodimeric pairs:
      TbSec23.1/TbSec24.2 and TbSec23.2/TbSec24.1. RNA interference silencing of each
      subunit is lethal but has minimal effects on trafficking of soluble and
      transmembrane proteins. However, silencing of the TbSec23.2/TbSec24.1 pair
      selectively impairs ER exit of GPI-anchored cargo. All four subunits colocalize
      to one or two ER exit sites (ERES), in close alignment with the postnuclear
      flagellar adherence zone (FAZ), and closely juxtaposed to corresponding Golgi
      clusters. These ERES are nucleated on the FAZ-associated ER. The Golgi matrix
      protein Tb Golgi reassembly stacking protein defines a region between the ERES
      and Golgi, suggesting a possible structural role in the ERES:Golgi junction. Our
      results confirm a selective mechanism for GPI-anchored cargo loading into COPII
      vesicles and a remarkable degree of streamlining in the early secretory pathway.
      This unusual architecture probably maximizes efficiency of VSG transport and
      fidelity in organellar segregation during cytokinesis.

PMID- 19759176
TI  - Interaction between Poly(ADP-ribose) and NuMA contributes to mitotic spindle pole
      assembly.
AB  - Poly(ADP-ribose) (pADPr), made by PARP-5a/tankyrase-1, localizes to the poles of
      mitotic spindles and is required for bipolar spindle assembly, but its molecular
      function in the spindle is poorly understood. To investigate this, we localized
      pADPr at spindle poles by immuno-EM. We then developed a concentrated mitotic
      lysate system from HeLa cells to probe spindle pole assembly in vitro.
      Microtubule asters assembled in response to centrosomes and Ran-GTP in this
      system. Magnetic beads coated with pADPr, extended from PARP-5a, also triggered
      aster assembly, suggesting a functional role of the pADPr in spindle pole
      assembly. We found that PARP-5a is much more active in mitosis than interphase.
      We used mitotic PARP-5a, self-modified with pADPr chains, to capture mitosis
      specific pADPr-binding proteins. Candidate binding proteins included the spindle
      pole protein NuMA previously shown to bind to PARP-5a directly. The rod domain of
      NuMA, expressed in bacteria, bound directly to pADPr. We propose that pADPr
      provides a dynamic cross-linking function at spindle poles by extending from
      covalent modification sites on PARP-5a and NuMA and binding noncovalently to NuMA
      and that this function helps promote assembly of exactly two poles.

PMID- 19759177
TI  - Rabex-5 is a Rab22 effector and mediates a Rab22-Rab5 signaling cascade in
      endocytosis.
AB  - Rabex-5 targets to early endosomes and functions as a guanine nucleotide exchange
      factor for Rab5. Membrane targeting is critical for Rabex-5 to activate Rab5 on
      early endosomes in the cell. Here, we report the identification of Rab22 as a
      binding site on early endosomes for direct recruitment of Rabex-5 and activation
      of Rab5, establishing a Rab22-Rab5 signaling relay to promote early endosome
      fusion. Rab22 in guanosine 5'-O-(3-thio)triphosphate-loaded form, but not
      guanosine diphosphate-loaded form, binds to the early endosomal targeting domain
      (residues 81-230) of Rabex-5 in pull-down assays. Rabex-5 targets to Rab22
      containing early endosomes, and Rab22 knockdown by short hairpin RNA abrogates
      the membrane targeting of Rabex-5 in the cell. In addition, coexpression of Rab22
      and Rab5 shows synergistic enlargement of early endosomes, and this synergy is
      dependent on Rabex-5, providing further support for the collaboration of the two
      Rab GTPases in regulation of endosome dynamics. This novel Rab22-Rabex-5-Rab5
      cascade is functionally important for the endocytosis and degradation of
      epidermal growth factor.

PMID- 19759178
TI  - Sox9 family members negatively regulate maturation and calcification of
      chondrocytes through up-regulation of parathyroid hormone-related protein.
AB  - Sox9 is a transcription factor that plays an essential role in chondrogenesis and
      has been proposed to inhibit the late stages of endochondral ossification.
      However, the molecular mechanisms underlying the regulation of chondrocyte
      maturation and calcification by Sox9 remain unknown. In this study, we attempted
      to clarify roles of Sox9 in the late stages of chondrocyte differentiation. We
      found that overexpression of Sox9 alone or Sox9 together with Sox5 and Sox6
      (Sox5/6/9) inhibited the maturation and calcification of murine primary
      chondrocytes and up-regulated parathyroid hormone-related protein (PTHrP)
      expression in primary chondrocytes and the mesenchymal cell line C3H10T1/2.
      Sox5/6/9 stimulated the early stages of chondrocyte proliferation and
      development. In contrast, Sox5/6/9 inhibited maturation and calcification of
      chondrocytes in organ culture. The inhibitory effects of Sox5/6/9 were rescued by
      treating with anti-PTHrP antibody. Moreover, Sox5/6/9 bound to the promoter
      region of the PTHrP gene and up-regulated PTHrP gene promoter activity.
      Interestingly, we also found that the Sox9 family members functionally
      collaborated with Ihh/Gli2 signaling to regulate PTHrP expression and chondrocyte
      differentiation. Our results provide novel evidence that Sox9 family members
      mediate endochondral ossification by up-regulating PTHrP expression in
      association with Ihh/Gli2 signaling.

PMID- 19759179
TI  - Expression and activity of phosphodiesterase isoforms during epithelial
      mesenchymal transition: the role of phosphodiesterase 4.
AB  - Epithelial-mesenchymal transition (EMT) has emerged as a critical event in the
      pathogenesis of organ fibrosis and cancer and is typically induced by the
      multifunctional cytokine transforming growth factor (TGF)-beta1. The present
      study was undertaken to evaluate the potential role of phosphodiesterases (PDEs)
      in TGF-beta1-induced EMT in the human alveolar epithelial type II cell line A549.
      Stimulation of A549 with TGF-beta1 induced EMT by morphological alterations and
      by expression changes of the epithelial phenotype markers E-cadherin, cytokeratin
      18, zona occludens-1, and the mesenchymal phenotype markers, collagen I,
      fibronectin, and alpha-smooth muscle actin. Interestingly, TGF-beta1 stimulation
      caused twofold increase in total cAMP-PDE activity, contributed mostly by PDE4.
      Furthermore, mRNA and protein expression demonstrated up-regulation of PDE4A and
      PDE4D isoforms in TGF-beta1-stimulated cells. Most importantly, treatment of TGF
      beta1 stimulated epithelial cells with the PDE4-selective inhibitor rolipram or
      PDE4 small interfering RNA potently inhibited EMT changes in a Smad-independent
      manner by decreasing reactive oxygen species, p38, and extracellular signal
      regulated kinase phosphorylation. In contrast, the ectopic overexpression of
      PDE4A and/or PDE4D resulted in a significant loss of epithelial marker E-cadherin
      but did not result in changes of mesenchymal markers. In addition, Rho kinase
      signaling activated by TGF-beta1 during EMT demonstrated to be a positive
      regulator of PDE4. Collectively, the findings presented herein suggest that TGF
      beta1 mediated up-regulation of PDE4 promotes EMT in alveolar epithelial cells.
      Thus, targeting PDE4 isoforms may be a novel approach to attenuate EMT-associated
      lung diseases such as pulmonary fibrosis and lung cancer.

PMID- 19759180
TI  - Glucose promotes stress resistance in the fungal pathogen Candida albicans.
AB  - Metabolic adaptation, and in particular the modulation of carbon assimilatory
      pathways during disease progression, is thought to contribute to the
      pathogenicity of Candida albicans. Therefore, we have examined the global impact
      of glucose upon the C. albicans transcriptome, testing the sensitivity of this
      pathogen to wide-ranging glucose levels (0.01, 0.1, and 1.0%). We show that, like
      Saccharomyces cerevisiae, C. albicans is exquisitely sensitive to glucose,
      regulating central metabolic genes even in response to 0.01% glucose. This
      indicates that glucose concentrations in the bloodstream (approximate range 0.05
      0.1%) have a significant impact upon C. albicans gene regulation. However, in
      contrast to S. cerevisiae where glucose down-regulates stress responses, some
      stress genes were induced by glucose in C. albicans. This was reflected in
      elevated resistance to oxidative and cationic stresses and resistance to an azole
      antifungal agent. Cap1 and Hog1 probably mediate glucose-enhanced resistance to
      oxidative stress, but neither is essential for this effect. However, Hog1 is
      phosphorylated in response to glucose and is essential for glucose-enhanced
      resistance to cationic stress. The data suggest that, upon entering the
      bloodstream, C. albicans cells respond to glucose increasing their resistance to
      the oxidative and cationic stresses central to the armory of immunoprotective
      phagocytic cells.

PMID- 19759181
TI  - SUN-1 and ZYG-12, mediators of centrosome-nucleus attachment, are a functional
      SUN/KASH pair in Caenorhabditis elegans.
AB  - Klarsicht/ANC-1/Syne/homology (KASH)/Sad-1/UNC-84 (SUN) protein pairs can act as
      connectors between cytoplasmic organelles and the nucleoskeleton. Caenorhabditis
      elegans ZYG-12 and SUN-1 are essential for centrosome-nucleus attachment.
      Although SUN-1 has a canonical SUN domain, ZYG-12 has a divergent KASH domain.
      Here, we establish that the ZYG-12 mini KASH domain is functional and, in
      combination with a portion of coiled-coil domain, is sufficient for nuclear
      envelope localization. ZYG-12 and SUN-1 are hypothesized to be outer and inner
      nuclear membrane proteins, respectively, and to interact, but neither their
      topologies nor their physical interaction has been directly investigated. We show
      that ZYG-12 is a type II outer nuclear membrane (ONM) protein and that SUN-1 is a
      type II inner nuclear membrane protein. The proteins interact in the luminal
      space of the nuclear envelope via the ZYG-12 mini KASH domain and a region of SUN
      1 that does not include the SUN domain. SUN-1 is hypothesized to restrict ZYG-12
      to the ONM, preventing diffusion through the endoplasmic reticulum. We establish
      that ZYG-12 is indeed immobile at the ONM by using fluorescence recovery after
      photobleaching and show that SUN-1 is sufficient to localize ZYG-12 in cells.
      This work supports current models of KASH/SUN pairs and highlights the diversity
      in sequence elements defining KASH domains.

PMID- 19759182
TI  - Filamin A regulates caveolae internalization and trafficking in endothelial
      cells.
AB  - Transcytosis via caveolae is critical for maintaining vascular homeostasis by
      regulating the tissue delivery of macromolecules, hormones, and lipids. In the
      present study, we test the hypothesis that interactions between F-actin cross
      linking protein filamin A and caveolin-1 facilitate the internalization and
      trafficking of caveolae. Small interfering RNA-mediated knockdown of filamin A,
      but not filamin B, reduced the uptake and transcytosis of albumin by
      approximately 35 and 60%, respectively, without altering the actin cytoskeletal
      structure or cell-cell adherens junctions. Mobility of both intracellular
      caveolin-1-green fluorescent protein (GFP)-labeled vesicles measured by
      fluorescence recovery after photobleaching and membrane-associated vesicles
      measured by total internal reflection-fluorescence microscopy was decreased in
      cells with reduced filamin A expression. In addition, in melanoma cells that lack
      filamin A (M2 cells), the majority of caveolin-1-GFP was localized on the plasma
      membrane, whereas in cells in which filamin A expression was reconstituted (A7
      cells and M2 cells transfected with filamin A-RFP), caveolin-1-GFP was
      concentrated in intracellular vesicles. Filamin A association with caveolin-1 in
      endothelial cells was confirmed by cofractionation of these proteins in density
      gradients, as well as by coimmunoprecipitation. Moreover, this interaction was
      enhanced by Src activation, associated with increased caveolin-1 phosphorylation,
      and blocked by Src inhibition. Taken together, these data suggest that filamin A
      association with caveolin-1 promotes caveolae-mediated transport by regulating
      vesicle internalization, clustering, and trafficking.

PMID- 19759183
TI  - CD26 expression in donor stem cell harvest and its correlation with engraftment
      in human haematopoietic stem cell transplantation: potential predictor of early
      engraftment.
AB  - BACKGROUND: The efficiency of haematopoietic stem and progenitor cells (HSPCs) is
      important when donor cell numbers are limiting. Stable white blood cell (WBC) and
      platelet engraftment is crucial for the outcome of haematopoietic stem cell
      transplantation (HSCT). DESIGN: This article evaluates CD26/dipeptidyl peptidase
      IV expression on mobilised peripheral blood stem cell (PBSC) harvest of donors
      and its correlation with engraftment in HSCT. We have analysed CD26 expression on
      cells in various gates, that is, lymphocytes, monocytes, neutrophils and all
      populations using flow cytometry tool. RESULTS: Ours is the first study on human
      mobilised PBSC harvest from cancer patients or allogeneic related donors (n = 28)
      to demonstrate that increased CD26 expression leads to early engraftment in
      transplanted cancer patients. Correlation of CD26 expression with WBC engraftment
      was statistically significant (lymphocyte gate: P < 0.00001; monocyte gate: P <
      0.00001; neutrophil gate: P < 0.00001; all populations: P < 0.00001). CD34
      expression is a known predictor of engraftment. Nevertheless, there was no
      correlation between CD34 and CD26 expression in these cases. CONCLUSIONS: This
      study has given important leads indicating that CD26 expression may be an
      independent predictor of engraftment. Further study with large number of patients
      as well as study on circulatory CD26 may add valuable information towards
      improving current knowledge on CD26.

PMID- 19759184
TI  - IVS10+12A>G polymorphism in hMSH2 gene associated with prognosis for patients
      with colorectal cancer.
AB  - BACKGROUND: The polymorphisms in DNA repair genes may contribute to a variation
      in the DNA repair capacity, thereby affecting the risk of carcinogenesis and
      prognosis of colorectal cancer. Accordingly, the present study analyzed 14
      polymorphisms in DNA repair genes and their impact on the prognosis for patients
      with colorectal cancer. MATERIALS AND METHODS: Three hundred and ninety-seven
      consecutive patients with curatively resected colorectal adenocarcinoma were
      enrolled in the present study. The genomic DNA was extracted from fresh
      colorectal tissue and 14 polymorphisms of DNA repair genes determined using a
      real-time PCR genotyping assay. RESULTS: The median age of the patients was 63
      years, and 218 (54.9%) patients had colon cancer, while 179 (45.1%) patients had
      rectal cancer. A multivariate survival analysis, including age, differentiation,
      carcinoembryonic antigen level, and stage, revealed a better survival for the
      patients with the combined IVS10+12AG and GG genotype than for the patients with
      the IVS10+12AA genotype [disease-free survival: hazard ratio (HR) 0.47, 95%
      confidence interval (CI) 0.30-0.75, P = 0.002; overall survival: HR 0.50, 95% CI
      0.26-0.98, P = 0.042]. None of the other polymorphisms was associated with
      survival. CONCLUSION: The IVS10+12A>G polymorphism in the hMSH2 gene was found to
      be an independent prognostic marker for patients with colorectal cancer.

PMID- 19759185
TI  - Stanford V program for locally extensive and advanced Hodgkin lymphoma: the
      Memorial Sloan-Kettering Cancer Center experience.
AB  - BACKGROUND: The Stanford group has reported excellent results with the Stanford V
      regimen for patients with bulky and/or advanced Hodgkin lymphoma (HL). However,
      Gobbi reported markedly inferior failure-free survival (FFS) comparing Stanford V
      to other regimens but included major deviations from the original program. We
      retrospectively examined whether treatment at our institution carefully following
      Stanford V guidelines would confirm the original Stanford outcome data. PATIENTS
      AND METHODS: From June 1995 to May 2002, 126 patients with either locally
      extensive or advanced HL were treated with the 12-week Stanford V chemotherapy
      program followed by 36-Gy involved-field radiotherapy to sites initially > or =5
      cm and/or to macroscopic splenic disease. Overall, 26% had stage IV disease and
      20% had international prognostic score (IPS) > or =4. Overall survival (OS),
      disease-specific survival, progression-free survival (PFS), FFS, and freedom from
      second relapse (FF2R) were determined. RESULTS: The 5- and 7-year OS were 90% and
      88%, respectively. The 5-year FFS was 78%. IPS > or =4 was a significant
      independent predictor of worse OS and PFS. The FF2R was 64% at 3 years.
      CONCLUSION: Stanford V with appropriate radiotherapy is a highly effective
      regimen for locally extensive and advanced HL.

PMID- 19759186
TI  - Surrogate end points for overall survival and local control in neoadjuvant rectal
      cancer trials: statistical evaluation based on the FFCD 9203 trial.
AB  - BACKGROUND: In resectable rectal cancer trials, pathological parameters are early
      preoperative treatment efficacy measures. Their validation as surrogate end
      points for long-term clinical outcomes would allow to reduce trial duration. The
      aim was to evaluate potential surrogates for overall survival (OS) and local
      control (LC) in preoperative T3/T4 rectal cancer trials. Candidate variables
      included ypT and ypN stages, T downstaging, tumor regression grade (TRG), and
      circumferential resection margin (CRM) status. PATIENTS AND METHODS: In the
      Federation Francophone de Cancerologie Digestive (FFCD) 9203 trial, 742 eligible
      patients were randomly assigned to receive preoperative radiotherapy with or
      without concurrent chemotherapy. Surrogacy was evaluated using Prentice criteria
      and the proportion of treatment effect (PTE) explained by each potential
      surrogate. RESULTS: None of the candidate surrogates fulfilled all Prentice
      criteria. Data analyses did not provide interpretable PTE measures for OS.
      Regarding LC, the highest PTE was reached by TRG, which explained 12% of the
      effect on local recurrence. This proportion may not exceed 41% [95% confidence
      interval (CI) -1% to 41%]. PTE explained by the CRM status was associated with a
      wide uncertainty (95% CI -81% to 105%), which does not exclude a potentially high
      degree of surrogacy. CONCLUSION: In the FFCD 9203 trial, pathological parameters
      were not surrogate for OS or LC.

PMID- 19759187
TI  - Are we representing the true population in oncology trials?

PMID- 19759188
TI  - Metabolic syndrome and cancer-related mortality among Korean men and women.
AB  - BACKGROUND: We examined the association between the metabolic syndrome and cancer
      mortality in Koreans. MATERIALS AND METHODS: This study included 42 336 men and
      32 168 women aged > or =20 years who took health examination and were followed up
      for 5.6 years. Mortality data were analyzed according to the metabolic syndrome.
      RESULTS: The relative risk (RR) and 95% confidence interval (CI) of cancer
      mortality in subjects with metabolic syndrome compared with subjects without
      metabolic syndrome was 1.41 (1.08-1.84) after adjustment for possible confounding
      factors. The association is significant only among men [RR 1.52 (1.10-2.10)], but
      not among women. The RRs and 95% CIs for cancer deaths in subjects with elevated
      body mass index, blood pressure, fasting glucose, and triglycerides were 1.36
      (1.07-1.71), 1.34 (1.07-1.69), 1.45 (1.14-1.86), and 1.60 (1.26-2.02) after
      mutual adjustment, respectively. Upon increasing the number of metabolic risk
      factors to 1, 2-3, and 4-5, the RRs and 95% CIs of death from cancer were 1.32
      (0.83-1.48), 1.47 (1.10-1.96), and 2.42 (1.25-4.68), respectively, with a graded
      fashion (P for trend < 0.005). CONCLUSION: Our results indicate that metabolic
      syndrome is a risk factor for cancer-related death in Korean adults. Prevention
      and management of the metabolic syndrome would be needed to reduce cancer
      mortality.

PMID- 19759189
TI  - A dendritic cell tumor in an HIV-infected patient: case report.

PMID- 19759190
TI  - Somatostatin receptor tissue distribution in lung neuroendocrine tumours: a
      clinicopathologic and immunohistochemical study of 218 'clinically aggressive'
      cases.
AB  - BACKGROUND: The management of pulmonary neuroendocrine tumours (NETs), with
      special reference to clinically aggressive carcinoids and large-cell
      neuroendocrine carcinomas (LCNECs), is poorly standardised and data about
      somatostatin receptor (SSTR) expression or therapeutic guidelines for
      somatostatin analogue administration are still debated. MATERIALS AND METHODS: A
      series of 218 lung NETs [24 metastatic typical carcinoids (TCs), 73 atypical
      carcinoids (ACs), 60 LCNECs and 61 surgically resected small-cell lung
      carcinomas] were investigated for SSTR types 2A and 3 tissue distribution using
      immunohistochemistry, in correlation with clinicopathologic parameters, outcome,
      scintigraphy and treatment. RESULTS: SSTRs were heterogeneously distributed with
      a significant progressive decrease from low- to high-grade forms. SSTR type 2A
      was strikingly overexpressed in metastatic TCs as compared with ACs and
      clinically benign TCs. SSTR tissue immunolocalization correlated with octreotide
      scintigraphy in 20 of 28 cases. CONCLUSION: The immunohistochemical determination
      of SSTRs, with special reference to low-grade/intermediate-grade tumours, may
      assist the clinical approach with somatostatin analogue-based diagnostic and
      therapeutic procedures in clinically aggressive pulmonary NETs.

PMID- 19759191
TI  - Fascin1 expression predicts poor prognosis in patients with nasopharyngeal
      carcinoma and correlates with tumor invasion.
AB  - BACKGROUND: The purpose of this study was to investigate prognostic significance
      of fascin1 in nasopharyngeal carcinoma (NPC) and evaluate the association of
      fascin1 with tumor invasion. MATERIALS AND METHODS: Immunohistochemical staining
      for fascin1 was carried out on paraffin-embedded tissue sections from 161
      patients with NPC. Data were subjected to statistical analysis with respect to
      clinicopathological variables and survival. Small interfering RNA (siRNA)
      approach was used to knockdown fascin1 expression in NPC cells to determine
      whether fascin1 contributes to tumor cell invasion. RESULTS: Immunohistochemical
      analysis showed that fascin1 was highly expressed in 95 (59.0%) of 161 paraffin
      embedded NPC tissues. Fascin1 expression was significantly correlated with
      clinical stage (P < 0.001) and N classification (P < 0.001). Statistical analysis
      showed that fascin1 expression was inversely correlated with both overall and
      disease-free survival of NPC patients. Multivariate analysis showed that fascin1
      expression was an independent prognostic indicator for patient's survival.
      Moreover, disruption of endogenous fascin1 expression in NPC cells using siRNA
      technique suppressed NPC cell invasiveness and decreased cell filopodia and
      lamellopodia. CONCLUSION: The present study indicates that fascin1 expression is
      inversely correlated with NPC patient survival and directly correlated with the
      malignant status of NPC.

PMID- 19759192
TI  - IL-12 deficiency suppresses 12-O-tetradecanoylphorbol-13-acetate-induced skin
      tumor development in 7,12-dimethylbenz(a)anthracene-initiated mouse skin through
      inhibition of inflammation.
AB  - Interleukin (IL)-12 deficiency exacerbates tumorigenesis in ultraviolet (UV)
      radiation-induced skin. Here, we assessed the effects of IL-12 deficiency on 12-O
      tetradecanoylphorbol-13-acetate (TPA)-induced tumor promotion in 7,12
      dimethylbenz(a)anthracene (DMBA)-initiated mouse skin. Using this two-stage
      chemical carcinogenesis protocol, we found that the development of DMBA/TPA
      induced skin tumors was diminished in IL-12p40-knockout mice than in their wild
      type counterparts. At the termination of the experiment (at 24 weeks), the skin
      tumor incidence and tumor multiplicity were significantly lower (P < 0.005) in
      interleukin-12-knockout (IL-12 KO) mice than in their wild-type counterparts, as
      was the malignant transformation of DMBA/TPA-induced papillomas to carcinomas (P
      < 0.01). Analysis of samples collected at the termination of the experiments for
      biomarkers of inflammation by immunohistochemical analysis, western blotting,
      enzyme-linked immunosorbent assay and real-time polymerase chain reaction
      revealed significantly lower levels of cyclooxygenase-2 (COX-2), prostaglandin
      (PG) E(2), proliferating cell nuclear antigen, cyclin D1 and the proinflammatory
      cytokines (tumor necrosis factor-alpha, IL-1beta and IL-6) in the DMBA/TPA
      treated tumors and tumor-uninvolved skin of IL-12 KO mice than the skin and
      tumors of DMBA/TPA-treated wild-type mice. Analysis of the skin 6 h after TPA
      treatment showed that the TPA-induced promotion of skin edema, inflammatory
      leukocyte infiltration, COX-2 expression and PGE(2) production was significantly
      lower in the skin of the IL-12-KO mice than their wild-type counterparts. These
      results indicate that DMBA/TPA-induced skin tumor development differs from UVB
      induced skin tumor development in that endogenous IL-12 acts to inhibit UVB
      induced skin tumor development and malignant progression of the skin tumors to
      carcinoma. In the case of DMBA/TPA-induced skin tumor development, the endogenous
      IL-12 modulates the tumor promoter stimulation of inflammatory responses.

PMID- 19759193
TI  - Selenium modifies the osteoblast inflammatory stress response to bone metastatic
      breast cancer.
AB  - Breast cancer frequently metastasizes to the skeleton resulting in bone
      degradation due to osteoclast activation. Metastases also downregulate
      differentiation and the bone-rebuilding function of osteoblasts. Moreover, cancer
      cells trigger osteoblast inflammatory stress responses. Pro-inflammatory
      mediators such as interleukin (IL)-6, monocyte chemoattractant protein-1 (MCP-1),
      cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), expressed by
      osteoblasts (MC3T3-E1) stimulated with human breast cancer cell (MDA-MB-231)
      conditioned medium, are pivotal to osteoclast activation and metastasis. Given
      that these genes are regulated by nuclear factor-kappaB (NF-kappaB), a redox
      sensitive transcription factor, we hypothesized that selenium (Se) could abrogate
      the inflammatory response to metastatic breast cancer cells by modulating NF
      kappaB. Caffeic acid phenethyl ester and parthenolide inhibited NF-kappaB
      activation, as seen by gel shift assays and immunoblotting for p65 in nuclear
      fractions, as well as decreased production of IL-6 and MCP-1. Supplementation of
      MC3T3-E1 with methylseleninic acid (MSA) (0.5 microM to 4 microM) reduced the
      activation of NF-kappaB leading to a decrease in IL-6, MCP-1, COX-2 and iNOS in
      response to MDA-MB-231 conditioned medium. Addition of MSA to osteoblasts for as
      little as 15 min suppressed activation of NF-kappaB suggesting that short-lived
      active metabolites might be involved. However, brief exposure to MSA also brought
      about an increase in selenoprotein glutathione peroxidase 1. In summary, our data
      indicate that the osteoblast response to metastatic breast cancer cells is
      regulated by NF-kappaB activation, which can be effectively suppressed by MSA
      either through short-lived active metabolites and/or selenoproteins. Thus, Se
      supplementation may prevent the osteoblast inflammatory response or dampen the
      vicious cycle established when breast cancer cells, osteoblasts and osteoclasts
      interact.

PMID- 19759194
TI  - TSH receptor activation and body composition.
AB  - The impacts of hyper and hypothyroidism on body composition, i.e. the relative
      quantity and quality of bone, adipose tissue and muscle, have traditionally been
      attributed uniquely to abnormal levels of free thyroid hormones. The presence of
      biologically active TSH receptors in bone, fat and muscle, raises the possibility
      that both thyroid hormones and TSH contribute to the changes in body composition
      associated with thyroid disease. This review evaluates the evidence for this in
      terms of the in vitro experimental approaches applied, data from in vivo sources
      (i.e. mouse models) and patient-based studies.

PMID- 19759195
TI  - 3D-SURFER: software for high-throughput protein surface comparison and analysis.
AB  - SUMMARY: We present 3D-SURFER, a web-based tool designed to facilitate high
      throughput comparison and characterization of proteins based on their surface
      shape. As each protein is effectively represented by a vector of 3D Zernike
      descriptors, comparison times for a query protein against the entire PDB take, on
      an average, only a couple of seconds. The web interface has been designed to be
      as interactive as possible with displays showing animated protein rotations, CATH
      codes and structural alignments using the CE program. In addition, geometrically
      interesting local features of the protein surface, such as pockets that often
      correspond to ligand binding sites as well as protrusions and flat regions can
      also be identified and visualized. AVAILABILITY: 3D-SURFER is a web application
      that can be freely accessed from: http://dragon.bio.purdue.edu/3d-surfer CONTACT:
      dkihara@purdue.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at
      Bioinformatics online.

PMID- 19759196
TI  - A dictionary to identify small molecules and drugs in free text.
AB  - MOTIVATION: From the scientific community, a lot of effort has been spent on the
      correct identification of gene and protein names in text, while less effort has
      been spent on the correct identification of chemical names. Dictionary-based term
      identification has the power to recognize the diverse representation of chemical
      information in the literature and map the chemicals to their database
      identifiers. RESULTS: We developed a dictionary for the identification of small
      molecules and drugs in text, combining information from UMLS, MeSH, ChEBI,
      DrugBank, KEGG, HMDB and ChemIDplus. Rule-based term filtering, manual check of
      highly frequent terms and disambiguation rules were applied. We tested the
      combined dictionary and the dictionaries derived from the individual resources on
      an annotated corpus, and conclude the following: (i) each of the different
      processing steps increase precision with a minor loss of recall; (ii) the overall
      performance of the combined dictionary is acceptable (precision 0.67, recall 0.40
      (0.80 for trivial names); (iii) the combined dictionary performed better than the
      dictionary in the chemical recognizer OSCAR3; (iv) the performance of a
      dictionary based on ChemIDplus alone is comparable to the performance of the
      combined dictionary. AVAILABILITY: The combined dictionary is freely available as
      an XML file in Simple Knowledge Organization System format on the web site
      http://www.biosemantics.org/chemlist.

PMID- 19759197
TI  - Integrative clustering of multiple genomic data types using a joint latent
      variable model with application to breast and lung cancer subtype analysis.
AB  - MOTIVATION: The molecular complexity of a tumor manifests itself at the genomic,
      epigenomic, transcriptomic and proteomic levels. Genomic profiling at these
      multiple levels should allow an integrated characterization of tumor etiology.
      However, there is a shortage of effective statistical and bioinformatic tools for
      truly integrative data analysis. The standard approach to integrative clustering
      is separate clustering followed by manual integration. A more statistically
      powerful approach would incorporate all data types simultaneously and generate a
      single integrated cluster assignment. METHODS: We developed a joint latent
      variable model for integrative clustering. We call the resulting methodology
      iCluster. iCluster incorporates flexible modeling of the associations between
      different data types and the variance-covariance structure within data types in a
      single framework, while simultaneously reducing the dimensionality of the
      datasets. Likelihood-based inference is obtained through the Expectation
      Maximization algorithm. RESULTS: We demonstrate the iCluster algorithm using two
      examples of joint analysis of copy number and gene expression data, one from
      breast cancer and one from lung cancer. In both cases, we identified subtypes
      characterized by concordant DNA copy number changes and gene expression as well
      as unique profiles specific to one or the other in a completely automated
      fashion. In addition, the algorithm discovers potentially novel subtypes by
      combining weak yet consistent alteration patterns across data types.
      AVAILABILITY: R code to implement iCluster can be downloaded at
      http://www.mskcc.org/mskcc/html/85130.cfm

PMID- 19759198
TI  - Genome analysis with inter-nucleotide distances.
AB  - MOTIVATION: DNA sequences can be represented by sequences of four symbols, but it
      is often useful to convert the symbols into real or complex numbers for further
      analysis. Several mapping schemes have been used in the past, but they seem
      unrelated to any intrinsic characteristic of DNA. The objective of this work was
      to find a mapping scheme directly related to DNA characteristics and that would
      be useful in discriminating between different species. Mathematical models to
      explore DNA correlation structures may contribute to a better knowledge of the
      DNA and to find a concise DNA description. RESULTS: We developed a methodology to
      process DNA sequences based on inter-nucleotide distances. Our main contribution
      is a method to obtain genomic signatures for complete genomes, based on the inter
      nucleotide distances, that are able to discriminate between different species.
      Using these signatures and hierarchical clustering, it is possible to build
      phylogenetic trees. Phylogenetic trees lead to genome differentiation and allow
      the inference of phylogenetic relations. The phylogenetic trees generated in this
      work display related species close to each other, suggesting that the inter
      nucleotide distances are able to capture essential information about the genomes.
      To create the genomic signature, we construct a vector which describes the inter
      nucleotide distance distribution of a complete genome and compare it with the
      reference distance distribution, which is the distribution of a sequence where
      the nucleotides are placed randomly and independently. It is the residual or
      relative error between the data and the reference distribution that is used to
      compare the DNA sequences of different organisms.

PMID- 19759199
TI  - Characterization of 1H NMR spectroscopic data and the generation of synthetic
      validation sets.
AB  - MOTIVATION: Common contemporary practice within the nuclear magnetic resonance
      (NMR) metabolomics community is to evaluate and validate novel algorithms on
      empirical data or simplified simulated data. Empirical data captures the complex
      characteristics of experimental data, but the optimal or most correct analysis is
      unknown a priori; therefore, researchers are forced to rely on indirect
      performance metrics, which are of limited value. In order to achieve fair and
      complete analysis of competing techniques more exacting metrics are required.
      Thus, metabolomics researchers often evaluate their algorithms on simplified
      simulated data with a known answer. Unfortunately, the conclusions obtained on
      simulated data are only of value if the data sets are complex enough for results
      to generalize to true experimental data. Ideally, synthetic data should be
      indistinguishable from empirical data, yet retain a known best analysis. RESULTS:
      We have developed a technique for creating realistic synthetic metabolomics
      validation sets based on NMR spectroscopic data. The validation sets are
      developed by characterizing the salient distributions in sets of empirical
      spectroscopic data. Using this technique, several validation sets are constructed
      with a variety of characteristics present in 'real' data. A case study is then
      presented to compare the relative accuracy of several alignment algorithms using
      the increased precision afforded by these synthetic data sets. AVAILABILITY:
      These data sets are available for download at
      http://birg.cs.wright.edu/nmr_synthetic_data_sets.

PMID- 19759200
TI  - Impact of genotype misclassification on genetic association estimates and the
      bayesian adjustment.
AB  - Genotypes of single nucleotide polymorphisms are subject to misclassification. If
      ignored, such misclassification can seriously distort the estimated genotype
      effects on the disease or outcome of interest. Validation data (gold standard or
      replicated surrogates) are required to assess the degree of misclassification and
      make adjustments. In practice, gold standard measurements may be unavailable or
      impractical. Collecting replicated surrogates is a reasonable option for
      validation data. In most practical applications, collecting replicated surrogates
      on all study subjects is not feasible; however, obtaining replicated surrogates
      on a subsample of the study population may be quite feasible. Generating
      duplicate data for a subsample of the study population is now common practice
      among genotyping laboratories. The authors propose a Bayesian method that can
      adjust for genotype misclassification using partial validation data. Simulation
      results show that the proposed method substantially reduces misclassification
      bias from the estimated genotype-disease association and provides appropriate
      uncertainty assessment, as well as improves other desirable properties of the
      estimated effects. The authors also provide an example showing the application of
      the proposed method to study data relating non-Hodgkin lymphoma to a single
      nucleotide polymorphism in the aryl hydrocarbon receptor gene.

PMID- 19759201
TI  - Sporadic Creutzfeldt-Jakob disease: discrete subtypes or a spectrum of disease?

PMID- 19759202
TI  - Language networks in semantic dementia.
AB  - Cognitive deficits in semantic dementia have been attributed to anterior temporal
      lobe grey matter damage; however, key aspects of the syndrome could be due to
      altered anatomical connectivity between language pathways involving the temporal
      lobe. The aim of this study was to investigate the left language-related cerebral
      pathways in semantic dementia using diffusion tensor imaging-based tractography
      and to combine the findings with cortical anatomical and functional magnetic
      resonance imaging data obtained during a reading activation task. The left
      inferior longitudinal fasciculus, arcuate fasciculus and fronto-parietal superior
      longitudinal fasciculus were tracked in five semantic dementia patients and eight
      healthy controls. The left uncinate fasciculus and the genu and splenium of the
      corpus callosum were also obtained for comparison with previous studies. From
      each tract, mean diffusivity, fractional anisotropy, as well as parallel and
      transverse diffusivities were obtained. Diffusion tensor imaging results were
      related to grey and white matter atrophy volume assessed by voxel-based
      morphometry and functional magnetic resonance imaging activations during a
      reading task. Semantic dementia patients had significantly higher mean
      diffusivity, parallel and transverse in the inferior longitudinal fasciculus. The
      arcuate and uncinate fasciculi demonstrated significantly higher mean
      diffusivity, parallel and transverse and significantly lower fractional
      anisotropy. The fronto-parietal superior longitudinal fasciculus was relatively
      spared, with a significant difference observed for transverse diffusivity and
      fractional anisotropy, only. In the corpus callosum, the genu showed lower
      fractional anisotropy compared with controls, while no difference was found in
      the splenium. The left parietal cortex did not show significant volume changes on
      voxel-based morphometry and demonstrated normal functional magnetic resonance
      imaging activation in response to reading items that stress sublexical
      phonological processing. This study shows that semantic dementia is associated
      with anatomical damage to the major superior and inferior temporal white matter
      connections of the left hemisphere likely involved in semantic and lexical
      processes, with relative sparing of the fronto-parietal superior longitudinal
      fasciculus. Fronto-parietal regions connected by this tract were activated
      normally in the same patients during sublexical reading. These findings
      contribute to our understanding of the anatomical changes that occur in semantic
      dementia, and may further help to explain the dissociation between marked single
      word and object knowledge deficits, but sparing of phonology and fluency in
      semantic dementia.

PMID- 19759203
TI  - A clinico-pathological study of subtypes in Parkinson's disease.
AB  - We have carried out a systematic review of the case files of 242 donors with
      pathologically verified Parkinson's disease at the Queen Square Brain Bank for
      Neurological Disorders in an attempt to corroborate the data-driven subtype
      classification proposed by Lewis and colleagues (Heterogeneity of Parkinson's
      disease in the early clinical stages using a data driven approach. J Neurol
      Neurosurg Psychiatry 2005; 76: 343-8). Cases were segregated into earlier disease
      onset (25%), tremor dominant (31%), non-tremor dominant (36%) and rapid disease
      progression without dementia (8%) subgroups. We found a strong association
      between a non-tremor dominant disease pattern and cognitive disability. The
      earlier disease onset group had the longest duration to death, and greatest delay
      to the onset of falls and cognitive decline. Patients with a tremor dominant
      disease pattern did not live significantly longer than non-tremor dominant
      patients and showed no difference in mean time to onset of falls and
      hallucinations. Rapid disease progression was associated with older age, early
      depression and early midline motor symptoms, and in 70% of the cases, tremulous
      onset. The non-tremor dominant subgroup had a significantly higher mean
      pathological grading of cortical Lewy bodies than all other groupings (P < 0.05)
      and more cortical amyloid-beta plaque load and cerebral amyloid angiopathy than
      early disease onset and tremor dominant groups (P = 0.047). An analysis of cases
      with pathologically defined neocortical Lewy body disease confirmed the link
      between bradykinetic onset, cognitive decline and Lewy body deposition in the
      neocortex. Although neuropathological examination failed to distinguish the other
      subtypes, the classification scheme was supported by an analysis of clinical data
      that were independent of the basic subgroup definitions.

PMID- 19759204
TI  - Case report. Intra-arterial chemotherapy for laryngeal cancer via a non
      bifurcating carotid artery.
AB  - The common carotid artery (CCA) usually divides into the internal carotid artery
      (ICA) and the external carotid artery (ECA). We present an extremely rare case of
      a non-bifurcating carotid artery through which intra-arterial chemotherapy for
      laryngeal cancer was administered. The CCA angiogram, as well as ultrasonographic
      evaluation of the carotid arteries, demonstrated a non-bifurcating CCA that
      subsequently constituted the ICA. Furthermore, several branches normally given
      off by the ECA arose directly from the single carotid artery. Superselective
      intra-arterial infusion of cis-diamminedichloroplatinum (II) (CDDP) was
      subsequently performed.

PMID- 19759205
TI  - Case report. Multilocular cystadenoma of the prostate presenting as a giant
      pelvic mass.
AB  - Here, we report the largest case of a multilocular cystadenoma of the prostate,
      causing visceral compression and symptoms of obstructive uropathy. The diagnostic
      and management dilemmas posed by this rare condition are discussed.

PMID- 19759206
TI  - Case report. Isolated complete congenital sternal cleft in an adult: MDCT imaging
      findings.
AB  - Sternal cleft is a very rare midline defect. Incomplete forms are more common
      than complete ones. In this challenging anomaly, the underlying mediastinal
      structures (especially the heart and great vessels) can easily be injured by
      external trauma. In addition, the deformity is cosmetically unpleasant and quite
      alarming to the young patient and the patient's family. In this report, we
      describe the multidetector CT (MDCT) images that demonstrate the complete sternal
      cleft.

PMID- 19759207
TI  - Case report. Glioblastoma multiforme presenting as a haemorrhagic minimally
      enhancing mass of the trigone.
AB  - Tumours of the trigone are rare, representing less than 2.5% of all intracranial
      tumours. The most common cause in adults is a meningioma. Glioblastoma multiforme
      of the trigone is extremely rare, with only six cases reported in the literature.
      We present a case of a glioblastoma multiforme of the trigone presenting in a 57
      year-old man with temporal lobe seizures. Imaging revealed a haemorrhagic
      minimally enhancing mass of the trigone. Histology showed a high-grade malignant
      glial-derived neoplasm of World Health Organization Grade IV.

PMID- 19759208
TI  - Case report. Tuberculous cervical lymphadenitis mimicking metastatic lymph nodes
      from papillary thyroid carcinoma.
AB  - We report two unusual cases of tuberculous lymphadenitis mimicking metastatic
      lymph nodes from papillary thyroid carcinoma (PTC). Pre-operative ultrasonography
      of the cervical nodes suggested a metastasis with cystic necrosis and
      calcification in PTC patients, but permanent pathology revealed tuberculosis
      lymphadenitis after neck dissection. In cases suspicious for metastatic cervical
      nodes in patients with PTC, fine-needle aspiration cytology may be indicated for
      the differential diagnosis of tuberculosis lymphadenitis, especially in those who
      have experienced tuberculosis in the past.

PMID- 19759209
TI  - Case report. Schwannoma of both intrahepatic and extrahepatic bile ducts: a rare
      case.
AB  - Schwannoma of the biliary tree is extremely uncommon, with only a few cases
      having been reported so far. They commonly present with obstructive jaundice.
      Although involvement of the extrahepatic duct is common, occurrence in the
      intrahepatic ducts has not been reported. We report a case of combined
      intrahepatic and extrahepatic schwannoma in a 46-year-old man presenting with
      obstructive jaundice.

PMID- 19759210
TI  - "Why have I got a 'dead ear', doctor"?

PMID- 19759211
TI  - The Staphylococcus aureus pSK41 plasmid-encoded ArtA protein is a master
      regulator of plasmid transmission genes and contains a RHH motif used in
      alternate DNA-binding modes.
AB  - Plasmids harbored by Staphylococcus aureus are a major contributor to the spread
      of bacterial multi-drug resistance. Plasmid conjugation and partition are
      critical to the dissemination and inheritance of such plasmids. Here, we
      demonstrate that the ArtA protein encoded by the S. aureus multi-resistance
      plasmid pSK41 is a global transcriptional regulator of pSK41 genes, including
      those involved in conjugation and segregation. ArtA shows no sequence homology to
      any structurally characterized DNA-binding protein. To elucidate the mechanism by
      which it specifically recognizes its DNA site, we obtained the structure of ArtA
      bound to its cognate operator, ACATGACATG. The structure reveals that ArtA is
      representative of a new family of ribbon-helix-helix (RHH) DNA-binding proteins
      that contain extended, N-terminal basic motifs. Strikingly, unlike most well
      studied RHH proteins ArtA binds its cognate operators as a dimer. However, we
      demonstrate that it is also able to recognize an atypical operator site by
      binding as a dimer-of-dimers and the extended N-terminal regions of ArtA were
      shown to be essential for this dimer-of-dimer binding mode. Thus, these data
      indicate that ArtA is a master regulator of genes critical for both horizontal
      and vertical transmission of pSK41 and that it can recognize DNA utilizing
      alternate binding modes.

PMID- 19759212
TI  - Involvement of p54(nrb), a PSF partner protein, in DNA double-strand break repair
      and radioresistance.
AB  - Mammalian cells repair DNA double-strand breaks (DSBs) via efficient pathways of
      direct, nonhomologous DNA end joining (NHEJ) and homologous recombination (HR).
      Prior work has identified a complex of two polypeptides, PSF and p54(nrb), as a
      stimulatory factor in a reconstituted in vitro NHEJ system. PSF also stimulates
      early steps of HR in vitro. PSF and p54(nrb) are RNA recognition motif-containing
      proteins with well-established functions in RNA processing and transport, and
      their apparent involvement in DSB repair was unexpected. Here we investigate the
      requirement for p54(nrb) in DSB repair in vivo. Cells treated with siRNA to
      attenuate p54(nrb) expression exhibited a delay in DSB repair in a gamma-H2AX
      focus assay. Stable knockdown cell lines derived by p54(nrb) miRNA transfection
      showed a significant increase in ionizing radiation-induced chromosomal
      aberrations. They also showed increased radiosensitivity in a clonogenic survival
      assay. Together, results indicate that p54(nrb) contributes to rapid and accurate
      repair of DSBs in vivo in human cells and that the PSF.p54(nrb) complex may thus
      be a potential target for radiosensitizer development.

PMID- 19759213
TI  - Multiplex primer prediction software for divergent targets.
AB  - We describe a Multiplex Primer Prediction (MPP) algorithm to build multiplex
      compatible primer sets to amplify all members of large, diverse and unalignable
      sets of target sequences. The MPP algorithm is scalable to larger target sets
      than other available software, and it does not require a multiple sequence
      alignment. We applied it to questions in viral detection, and demonstrated that
      there are no universally conserved priming sequences among viruses and that it
      could require an unfeasibly large number of primers ( approximately 3700 18-mers
      or approximately 2000 10-mers) to generate amplicons from all sequenced viruses.
      We then designed primer sets separately for each viral family, and for several
      diverse species such as foot-and-mouth disease virus (FMDV), hemagglutinin (HA)
      and neuraminidase (NA) segments of influenza A virus, Norwalk virus, and HIV-1.
      We empirically demonstrated the application of the software with a multiplex set
      of 16 short (10 nt) primers designed to amplify the Poxviridae family to produce
      a specific amplicon from vaccinia virus.

PMID- 19759214
TI  - RNA-protein binding kinetics in an automated microfluidic reactor.
AB  - Microfluidic chips can automate biochemical assays on the nanoliter scale, which
      is of considerable utility for RNA-protein binding reactions that would otherwise
      require large quantities of proteins. Unfortunately, complex reactions involving
      multiple reactants cannot be prepared in current microfluidic mixer designs, nor
      is investigation of long-time scale reactions possible. Here, a microfluidic
      'Riboreactor' has been designed and constructed to facilitate the study of
      kinetics of RNA-protein complex formation over long time scales. With computer
      automation, the reactor can prepare binding reactions from any combination of
      eight reagents, and is optimized to monitor long reaction times. By integrating a
      two-photon microscope into the microfluidic platform, 5-nl reactions can be
      observed for longer than 1000 s with single-molecule sensitivity and negligible
      photobleaching. Using the Riboreactor, RNA-protein binding reactions with a
      fragment of the bacterial 30S ribosome were prepared in a fully automated fashion
      and binding rates were consistent with rates obtained from conventional assays.
      The microfluidic chip successfully combines automation, low sample consumption,
      ultra-sensitive fluorescence detection and a high degree of reproducibility. The
      chip should be able to probe complex reaction networks describing the assembly of
      large multicomponent RNPs such as the ribosome.

PMID- 19759215
TI  - Genome-wide colonization of gene regulatory elements by G4 DNA motifs.
AB  - G-quadruplex (or G4 DNA), a stable four-stranded structure found in guanine-rich
      regions, is implicated in the transcriptional regulation of genes involved in
      growth and development. Previous studies on the role of G4 DNA in gene regulation
      mostly focused on genomic regions proximal to transcription start sites (TSSs).
      To gain a more comprehensive understanding of the regulatory role of G4 DNA, we
      examined the landscape of potential G4 DNA (PG4Ms) motifs in the human genome and
      found that G4 motifs, not restricted to those found in the TSS-proximal regions,
      are bias toward gene-associated regions. Significantly, analyses of G4 motifs in
      seven types of well-known gene regulatory elements revealed a constitutive
      enrichment pattern and the clusters of G4 motifs tend to be colocalized with
      regulatory elements. Considering our analysis from a genome evolutionary
      perspective, we found evidence that the occurrence and accumulation of certain
      progenitors and canonical G4 DNA motifs within regulatory regions were
      progressively favored by natural selection. Our results suggest that G4 DNA
      motifs are 'colonized' in regulatory regions, supporting a likely genome-wide
      role of G4 DNA in gene regulation. We hypothesize that G4 DNA is a regulatory
      apparatus situated in regulatory elements, acting as a molecular switch that can
      modulate the role of the host functional regions, by transition in DNA structure.

PMID- 19759216
TI  - Transcription from bacteriophage lambda pR promoter is regulated independently
      and antagonistically by DksA and ppGpp.
AB  - The stringent response effector, guanosine tetraphosphate (ppGpp), adjust gene
      expression and physiology in bacteria, by affecting the activity of various
      promoters. RNA polymerase-interacting protein, DksA, was proposed to be the co
      factor of ppGpp effects; however, there are reports suggesting independent roles
      of these regulators. Bacteriophage lambda major lytic promoter, pR, is down
      regulated by the stringent response and ppGpp. Here, we present evidence that
      DksA significantly stimulates pR-initiated transcription in vitro in the
      reconstituted system. DksA is also indispensable for pR activity in vivo. DksA
      mediated activation of pR-initiated transcription is predominant over ppGpp
      effects in the presence of both regulators in vitro. The possible role of the
      opposite regulation by ppGpp and DksA in lambda phage development is discussed.
      The major mechanism of DksA-mediated activation of transcription from pR involves
      facilitating of RNA polymerase binding to the promoter region, which results in
      more productive transcription initiation. Thus, our results provide evidence for
      the first promoter inhibited by ppGpp that can be stimulated by the DksA protein
      both in vivo and in vitro. Therefore, DksA role could be not only independent but
      antagonistic to ppGpp in transcription regulation.

PMID- 19759217
TI  - Molecular and phenotypic evaluation of Lichtheimia corymbifera (formerly Absidia
      corymbifera) complex isolates associated with human mucormycosis: rehabilitation
      of L. ramosa.
AB  - Thirty-eight isolates (including 28 isolates from patients) morphologically
      identified as Lichtheimia corymbifera (formerly Absidia corymbifera) were studied
      by sequence analysis (analysis of the internal transcribed spacer [ITS] region of
      the ribosomal DNA, the D1-D2 region of 28S, and a portion of the elongation
      factor 1alpha [EF-1alpha] gene). Phenotypic characteristics, including
      morphology, antifungal susceptibility, and carbohydrate assimilation, were also
      determined. Analysis of the three loci uncovered two well-delimited clades. The
      maximum sequence similarity values between isolates from both clades were 66, 95,
      and 93% for the ITS, 28S, and EF-1alpha loci, respectively, with differences in
      the lengths of the ITS sequences being detected (763 to 770 bp for isolates of
      clade 1 versus 841 to 865 bp for isolates of clade 2). Morphologically, the
      shapes and the sizes of the sporangiospores were significantly different among
      the isolates from both clades. On the basis of the molecular and morphological
      data, we considered isolates of clade 2 to belong to a different species named
      Lichtheimia ramosa because reference strains CBS 269.65 and CBS 270.65 (which
      initially belonged to Absidia ramosa) clustered within this clade. As neotype A.
      corymbifera strain CBS 429.75 belongs to clade 1, the name L. corymbifera was
      conserved for clade 1 isolates. Of note, the amphotericin B MICs were
      significantly lower for L. ramosa than for L. corymbifera (P < 0.005) but were
      always <or=0.5 microg/ml for both species. Among the isolates tested, the
      assimilation of melezitose was positive for 67% of the L. ramosa isolates and
      negative for all L. corymbifera isolates. In conclusion, this study reveals that
      two Lichtheimia species are commonly associated with mucormycosis in humans.

PMID- 19759218
TI  - Evaluation of a new test, genotype HelicoDR, for molecular detection of
      antibiotic resistance in Helicobacter pylori.
AB  - The eradication rate of Helicobacter pylori by standard therapy is decreasing due
      to antibiotic resistance, mainly to clarithromycin. Our aim was to provide a new
      molecular test to guide the treatment of new and relapsed cases. We first studied
      126 H. pylori strains for phenotypic (MIC) and genotypic resistance to
      clarithromycin (rrl mutation) and levofloxacin (gyrA mutation) and then developed
      a DNA strip genotyping test on the basis of the correlation results and
      literature data. Clinical strains (n = 92) and gastric biopsy specimens
      containing H. pylori (n = 105) were tested blindly with the new molecular test
      GenoType HelicoDR. The presence of mutations or the absence of hybridization with
      wild-type sequences was predictive, in rrl for clarithromycin resistance in 91
      cases (mostly the A2147G mutation) and in gyrA for levofloxacin resistance in 58
      cases (mutations at codon 87 or 91). Genotyping revealed a mix of genotypes in
      33% of the cases, reflecting a coinfection or selection for resistant mutants.
      The sensitivity and specificity of detecting resistance were 94% and 99% for
      clarithromycin and 87% and 98.5% for levofloxacin, respectively. The concordance
      scores were 0.96 for clarithromycin and 0.94 for levofloxacin. With global
      resistance rates of 46% for clarithromycin and 25% for levofloxacin, which were
      observed for consecutive positive biopsy specimens from 2007 and 2008, the
      positive and negative predictive values for detecting resistance were 99% and 94%
      for clarithromycin and 96% and 96% for fluoroquinolone. GenoType HelicoDR is
      efficient at detecting mutations predictive of antibiotic resistance in H. pylori
      when applied to strains or directly to gastric biopsy specimens.

PMID- 19759219
TI  - False-negative results of a validated real-time PCR protocol for diagnosis of
      newcastle disease due to genetic variability of the matrix gene.

PMID- 19759220
TI  - Emergence in Italy of Klebsiella pneumoniae sequence type 258 producing KPC-3
      Carbapenemase.

PMID- 19759221
TI  - Mycobacterium tuberculosis strains with highly discordant rifampin susceptibility
      test results.
AB  - The objectives of this study were to investigate the origin of highly discordant
      rifampin (rifampicin) (RMP) drug susceptibility test results obtained for
      Mycobacterium tuberculosis strains during proficiency testing. Nine Supra
      National Tuberculosis Reference Laboratories tested the RMP susceptibilities of
      19 selected M. tuberculosis strains, using standard culture-based methods. The
      strains were classified as definitely resistant (R) (n = 6) or susceptible (S) (n
      = 2) or probably resistant (PR) (n = 8) or susceptible (PS) (n = 3) based on rpoB
      mutations and treatment outcome. All methods yielded a susceptible result for the
      two S and three PS strains lacking an rpoB mutation and a resistant result for
      one R strain with a Ser531Leu mutation and one PR strain with a double mutation.
      Although the remaining 12 R and PR strains had rpoB mutations (four Asp516Tyr,
      three Leu511Pro, two Leu533Pro, one each His526Leu/Ser, and one Ile572Phe), they
      were all susceptible by the radiometric Bactec 460TB or Bactec 960 MGIT methods.
      In contrast, only one was susceptible by the proportion method on Lowenstein
      Jensen medium and two on Middlebrook 7H10 agar. Low-level but probably clinically
      relevant RMP resistance linked to specific rpoB mutations is easily missed by
      standard growth-based methods, particularly the automated broth-based systems.
      Further studies are required to confirm these findings, to determine the
      frequency of these low-level-resistant isolates, and to identify technical
      improvements that may identify such strains.

PMID- 19759222
TI  - Non-spa-typeable clinical Staphylococcus aureus strains are naturally occurring
      protein A mutants.
AB  - Staphylococcus aureus is a major human pathogen responsible for increasing the
      prevalence of community- and hospital-acquired infections. Protein A (SpA) is a
      key virulence factor of S. aureus and is highly conserved. Sequencing of the
      variable-number tandem-repeat region of SpA (spa typing) provides a rapid and
      reliable method for epidemiological studies. Rarely, non-spa-typeable S. aureus
      strains are encountered. The reason for this is not known. In this study, we
      characterized eight non-spa-typeable bacteremia isolates. Sequencing of the
      entire spa locus was successful for five strains and revealed various mutations
      of spa, all of which included a deletion of immunoglobulin G binding domain C, in
      which the upper primer for spa typing is located, while two strains were truly
      spa negative. This is the first report demonstrating that nontypeability of S.
      aureus by spa sequencing is due either to mutation or to a true deficiency of
      spa.

PMID- 19759223
TI  - Evidence of pathogenic subgroups among atypical enteropathogenic Escherichia coli
      strains.
AB  - We describe the characterization of 126 atypical enteropathogenic Escherichia
      coli (aEPEC) isolates from 1,749 Brazilian children. Classic aEPEC strains were
      more frequently found in children with diarrhea than in controls (P < 0.001),
      showing their importance as acute diarrhea agents in our country. Only aEPEC
      strains carrying either the ehxA or paa gene were significantly associated with
      diarrhea.

PMID- 19759224
TI  - Airway obstruction is increased in pneumocystis-colonized human immunodeficiency
      virus-infected outpatients.
AB  - We investigated the relationship of Pneumocystis colonization, matrix
      metalloprotease levels in sputum, and airway obstruction in a cohort of human
      immunodeficiency virus (HIV)-infected outpatients. Pneumocystis-colonized
      subjects had worse obstruction of airways and higher levels of matrix
      metalloprotease-12 in sputa, suggesting that Pneumocystis colonization may be
      important in HIV-associated chronic obstructive pulmonary disease.

PMID- 19759225
TI  - Two distinct clones of methicillin-resistant Staphylococcus aureus (MRSA) with
      the same USA300 pulsed-field gel electrophoresis profile: a potential pitfall for
      identification of USA300 community-associated MRSA.
AB  - Analysis of methicillin-resistant Staphylococcus aureus (MRSA) characterized as
      USA300 by pulsed-field gel electrophoresis identified two distinct clones. One
      was similar to community-associated USA300 MRSA (ST8-IVa, t008, and Panton
      Valentine leukocidin positive). The second (ST8-IVa, t024, and PVL negative) had
      different molecular characteristics and epidemiology, suggesting independent
      evolution. We recommend spa typing and/or PCR to discriminate between the two
      clones.

PMID- 19759226
TI  - Molecular and phenotypic characteristics of methicillin-resistant and vancomycin
      intermediate staphylococcus aureus isolates from patients with septic arthritis.
AB  - Staphylococcus aureus is one of the most common pathogens in community- and
      hospital-associated infections and frequently causes severe and intractable
      infections in osteoarticular tissues. S. aureus isolates that are resistant to
      methicillin (meticillin) (MRSA isolates) and intermediately resistant to
      vancomycin (VISA isolates) have emerged. In this report, we described two
      patients, one female and one male, diagnosed with septic arthritis due to S.
      aureus infections. A total of 13 MRSA isolates were obtained from these two
      patients. All but one isolate belonged to the VISA group. All seven isolates from
      the female patient were determined to be community associated, multilocus
      sequence type (MLST) 59, and staphylococcal cassette chromosome mecA (SCCmec)
      type IV; had direct repeat units (DRUs) of nine repeats; were spa type t437; and
      were susceptible to sulfa and quinolone antibiotics. The other six isolates, from
      the male patient, were determined to be hospital associated, MLST 239, and SCCmec
      type III; had DRUs of 14 repeats; were spa type t037; and were resistant to sulfa
      and quinolone antibiotics. All 13 MRSA isolates were in agr group I, were pvl
      negative, and showed no evidence of any association between vancomycin resistance
      and autolysis.

PMID- 19759227
TI  - Characterization of fHbp, nhba (gna2132), nadA, porA, sequence type (ST), and
      genomic presence of IS1301 in group B meningococcal ST269 clonal complex isolates
      from England and Wales.
AB  - Highly effective glycoconjugate vaccines exist against four of the five major
      pathogenic groups of meningococci: A, C, W-135, and Y. An equivalent vaccine
      against group B meningococci (menB) has remained elusive due to the poorly
      immunogenic capsular polysaccharide. A promising alternative, the investigational
      recombinant menB (rMenB)- outer membrane vesicle (OMV) vaccine, contains fHBP,
      NHBA (previously GNA2132), NadA, and outer membrane vesicles (OMVs) from the New
      Zealand MeNZB vaccine. MenB currently accounts for 90% of meningococcal disease
      in England and Wales, where the multilocus sequence type (ST) 269 (ST269) clonal
      complex (cc269) has recently expanded to account for a third of menB cases. To
      assess the potential cc269 coverage of the rMenB-OMV vaccine, English and Welsh
      cc269 isolates from the past decade were genetically characterized with respect
      to fHBP, NHBA, and NadA. All of the isolates harbored fHbp and nhba alleles,
      while 98% of the cc269 isolates were devoid of nadA. Subvariant profiling of
      fHbp, nhba, and porA against STs revealed the presence of two broadly distinct
      and well-defined clusters of isolates, centered around ST269 and ST275,
      respectively. An additional molecular marker, insertion sequence IS1301, was
      found to be present in 100% and <2% of isolates of the respective clusters. On
      the basis of the genetic data, the potential rMenB-OMV coverage of cc269 in
      England and Wales is high (up to 100%) within both clusters. Expression studies
      and serum bactericidal antibody assays will serve to enhance predictions of
      coverage and will augment ongoing studies regarding the significance of IS1301
      within the ST269 cluster.

PMID- 19759228
TI  - Epidemiology and clinical presentations of human coronavirus NL63 infections in
      hong kong children.
AB  - Human coronavirus NL63 (HCoV-NL63) has been found in children presenting with
      respiratory tract infections (RTIs). However, the epidemiology and clinical
      course of this newly identified virus have not been fully elucidated. This study
      investigated the epidemiology, seasonality, and clinical features of HCoV-NL63 in
      Hong Kong children. This study consisted of two cohorts of children hospitalized
      in a university-affiliated teaching hospital. In the 12-month retrospective part
      of the study, reverse transcription-PCR was used to detect HCoVs in
      nasopharyngeal aspirates (NPAs). Positive samples were sequenced to confirm the
      identity of the virus and to determine its phylogenetic relationship with the
      HCoV-NL63 strains found elsewhere. The second part covered a subsequent 12-month
      period in which patients were prospectively recruited. Altogether, 1,981 and
      1,001 NPA specimens were studied in 2005-2006 and 2006-2007, respectively.
      Seventy-four (2.5%) HCoV isolates were identified and consisted of 17 (0.6%) HCoV
      NL63 isolates, 37 (1.2%) HCoV-OC43 isolates, 14 (0.5%) HCoV-HKU1 isolates, and 6
      (0.2%) HCoV-229E isolates. HCoV-NL63 infection was more common in 2006-2007 than
      2005-2006 (1.2% and 0.3%, respectively; P = 0.006). From 2005 to 2007, the peak
      season for HCoV-NL63 infection was in September-October, which was earlier than
      the peak for HCoV-OC43 infections (December-January). HCoV-NL63-infected patients
      were younger and more likely to have croup, febrile convulsions, and acute
      gastroenteritis. The majority of local HCoV-NL63 isolates were phylogenetically
      closely related to those found in Belgium and The Netherlands. In conclusion,
      HCoV-NL63 is an important yet uncommon virus among our hospitalized children with
      acute RTIs.

PMID- 19759229
TI  - Chronic hepatitis, hepatic dysplasia, fibrosis, and biliary hyperplasia in
      hamsters naturally infected with a novel Helicobacter classified in the H. bilis
      cluster.
AB  - We recently described helicobacter-associated progressive, proliferative, and
      dysplastic typhlocolitis in aging (18- to 24-month-old) Syrian hamsters. Other
      pathogens associated with typhlocolitis in hamsters, Clostridium difficile,
      Lawsonia intracellularis, and Giardia spp., were not indentified. The presence of
      Helicobacter genus-specific DNA was noted by PCR in cecal and paraffin-embedded
      liver samples from aged hamsters by the use of Helicobacter-specific PCR primers.
      By 16S rRNA analysis, the Helicobacter sp. isolated from the liver tissue was
      identical to the cecal isolates from hamsters. The six hamster 16S rRNA sequences
      form a genotypic cluster most closely related to Helicobacter sp. Flexispira
      taxon 8, part of the Helicobacter bilis/H. cinaedi group. Livers from aged
      helicobacter-infected hamsters showed various stages of predominantly
      portocentric and, to a lesser extent, perivenular fibrosis. Within nodules, there
      was cellular atypia consistent with nodular dysplasia. The livers also exhibited
      a range of chronic active portal/interface and lobular inflammation, with
      significant portal hepatitis being present. The inflammation was composed of a
      mixture of lymphocytes, neutrophils, and macrophages, indicative of its chronic
      active nature in these aged hamsters infected with Helicobacter spp. The
      isolation of novel Helicobacter spp., their identification by PCR from the
      diseased livers of aged hamsters, and their taxonomic classification as belonging
      to the Helicobacter bilis cluster strengthen the argument that H. bilis and
      closely related Helicobacter spp. play an etiological role in hepatobiliary
      disease in both animals and humans.

PMID- 19759230
TI  - Foot-and-mouth disease virus antigen detection enzyme-linked immunosorbent assay
      using multiserotype-reactive monoclonal antibodies.
AB  - Monoclonal antibody (MAb)-based sandwich direct enzyme-linked immunosorbent assay
      (MSD-ELISA) methods that can detect foot-and-mouth disease virus (FMDV) antigens,
      both multiserotype (MSD-ELISA/MS) (for O, A, C, and Asia 1) and single-serotype
      (MSD-ELISA/SS) (for O, A, and Asia 1, specifically), were developed. MAb 1H5 was
      used as an antigen-trapping antibody that reacted with all seven serotypes of
      FMDV. The MAbs 71F2, 70C4, 16C6, and 7C2 were used as peroxidase-labeled
      detecting antibodies for multiple serotypes (O, A, C, and Asia 1), type O, type
      A, and type Asia 1, respectively, in both MSD-ELISA/MS and MSD-ELISA/SS. Our MSD
      ELISAs showed high specificity. They produced a very low background of negative
      samples (buffer, plasma, and saliva) and were able to detect FMDV antigens from
      clinical samples (plasma and saliva), with results correlating with those of real
      time reverse transcription-PCR. In terms of sensitivity, the MSD-ELISAs showed
      higher optical density values against each diluted serotype antigen than the
      indirect sandwich ELISA method, which is currently recommended in the manual of
      the World Organization for Animal Health. The sensitivity and specificity of the
      MSD-ELISAs seem to be sufficient for the antigenic diagnosis of FMDV.

PMID- 19759231
TI  - Antigenemia in patients with mediterranean visceral leishmaniasis.
AB  - Antigenemia in patients with Mediterranean visceral leishmaniasis (MVL) due to
      Leishmania infantum was retrospectively assessed by sandwich enzyme-linked
      immunosorbent assay (ELISA). Circulating Leishmania antigens, partially in free
      form, were in evidence in 53% of serum samples from immunocompetent individuals
      with MVL. Following successful therapy, antigenemia decline as measured by ELISA
      was more pronounced than antibody decrease.

PMID- 19759232
TI  - Clinical and resistance consequences of misquantification of plasma and
      cerebrospinal fluid human immunodeficiency virus type 1 (HIV-1) RNA in samples
      from an HIV-1 subtype G-infected patient.
AB  - Human immunodeficiency virus (HIV) load is the main marker used to monitor
      antiviral treatment efficacy and resistance. We report a case of
      underquantification of HIV type 1 (HIV-1) RNA in plasma and cerebrospinal fluid
      from an HIV-1 subtype G-infected woman, leading to delayed diagnosis of HIV
      encephalitis and to the emergence of drug resistance.

PMID- 19759233
TI  - Uncovering the footprint of positive selection on the X chromosome of Drosophila
      melanogaster.
AB  - A usual approach to detect the spatial footprint left by recent adaptive events
      has been to follow up putative candidates emerging from multilocus scans of
      variation by sequencing additional fragments. We have used a similar experimental
      and analytical approach to study variation at 15 independently evolving and
      randomly chosen regions of the X chromosome of Drosophila melanogaster. These
      incompletely sequenced regions, each extending over approximately 40 kb, were
      subjected to two tests of positive selection that take into account the spatial
      distribution of nucleotide variation. Our analysis of variation at these genomic
      regions in a European population of D. melanogaster has allowed us to uncover a
      candidate region for positive selection and to empirically evaluate the
      comparative performance of the two tests of selection under a bottleneck
      scenario. Moreover, the boundaries here estimated for both the rate of adaptive
      substitution (delta) and the average selection coefficient (s) would support
      previous estimates obtained by maximum likelihood that suggest rather strong but
      uncommon positive selection.

PMID- 19759234
TI  - Evolutionary dynamics of rhodopsin type 2 opsins in vertebrates.
AB  - Among the five groups of visual pigments in vertebrates, the rhodopsin type 2
      (RH2) group shows the largest number of gene duplication events. We have isolated
      three intact and one nonfunctional RH2 opsin genes each from Northern lampfish
      (Stenobrachius leucopsarus) and scabbardfish (Lepidopus fitchi). Using the
      deduced amino acid sequences of these and other representative RH2 opsin genes in
      vertebrates, we have estimated the divergence times and evolutionary rates of
      amino acid substitution at various stages of RH2 opsin evolution. The results
      show that the duplications of the lampfish and scabbardfish RH2 opsins have
      occurred approximately 60 and approximately 30 million years ago (Ma),
      respectively. The evolutionary rates of RH2 opsins in the early vertebrate
      ancestors were approximately 0.25 x 10(-9)/site/year, which increased to
      approximately 1 x 10(-9) to 3 x 10(-9)/site/year in euteleost lineages and to
      approximately 0.3 x 10(-9) to 0.5 x 10(-9)/site/year in coelacanth and tetrapods.

PMID- 19759235
TI  - Distributions of selectively constrained sites and deleterious mutation rates in
      the hominid and murid genomes.
AB  - Protein-coding sequences make up only about 1% of the mammalian genome. Much of
      the remaining 99% has been long assumed to be junk DNA, with little or no
      functional significance. Here, we show that in hominids, a group with
      historically low effective population sizes, all classes of noncoding DNA evolve
      more slowly than ancestral transposable elements and so appear to be subject to
      significant evolutionary constraints. Under the nearly neutral theory, we
      expected to see lower levels of selective constraints on most sequence types in
      hominids than murids, a group that is thought to have a higher effective
      population size. We found that this is the case for many sequence types examined,
      the most extreme example being 5'UTRs, for which constraint in hominids is only
      about one-third that of murids. Surprisingly, however, we observed higher
      constraints for some sequence types in hominids, notably 4-fold sites, where
      constraint is more than twice as high as in murids. This implies that more than
      about one-fifth of mutations at 4-fold sites are effectively selected against in
      hominids. The higher constraint at 4-fold sites in hominids suggests a more
      complex protein-coding gene structure than murids and indicates that methods for
      detecting selection on protein-coding sequences (e.g., using the d(N)/d(S)
      ratio), with 4-fold sites as a neutral standard, may lead to biased estimates,
      particularly in hominids. Our constraint estimates imply that 5.4% of nucleotide
      sites in the human genome are subject to effective negative selection and that
      there are three times as many constrained sites within noncoding sequences as
      within protein-coding sequences. Including coding and noncoding sites, we
      estimate that the genomic deleterious mutation rate U = 4.2. The mutational load
      predicted under a multiplicative model is therefore about 99% in hominids.

PMID- 19759236
TI  - Molecular evolutionary dynamics of Ross River virus and implications for vaccine
      efficacy.
AB  - Ross River virus (RRV) is a mosquito-borne member of the genus Alphavirus that
      causes epidemic polyarthritis in humans, costing the Australian health system at
      least US$10 million annually. Recent progress in RRV vaccine development requires
      accurate assessment of RRV genetic diversity and evolution, particularly as they
      may affect the utility of future vaccination. In this study, we provide novel RRV
      genome sequences and investigate the evolutionary dynamics of RRV from time
      structured E2 gene datasets. Our analysis indicates that, although RRV evolves at
      a similar rate to other alphaviruses (mean evolutionary rate of approx. 8x10(-4)
      nucleotide substitutions per site year(-1)), the relative genetic diversity of
      RRV has been continuously low through time, possibly as a result of purifying
      selection imposed by replication in a wide range of natural host and vector
      species. Together, these findings suggest that vaccination against RRV is
      unlikely to result in the rapid antigenic evolution that could compromise the
      future efficacy of current RRV vaccines.

PMID- 19759237
TI  - A region at the left end of the fowl adenovirus 9 genome that is non-essential in
      vitro has consequences in vivo.
AB  - The regions at the left and right ends of fowl adenovirus (FAdV) genomes are not
      well-characterized in comparison to those of human adenoviruses. Using a series
      of deletion mutants, we analysed a 2.4 kb region near the left end of the FAdV-9
      genome (nt 400-2782) that contains packaging-signal motifs VI and VII and open
      reading frames (ORFs) 0, 1, 1A, 1B, 1C and 2. Viable viruses with specific
      deletions in this region had wild-type characteristics in vitro, as measured by
      cytopathic effect, plaque morphology, virus titres and growth kinetics. However,
      one mutant (FAdV-9Delta4), which lacked these ORFs and retained the packaging
      motifs, did not replicate at wild-type levels in vivo, as judged in infected eggs
      by virus titres in allantoic fluid and in infected chickens by antibody
      responses, virus titres in faeces and virus genome copy numbers in tissues. These
      findings indicate that some of the ORFs in this region, although dispensable in
      vitro, are important for in vivo replication of FAdV-9.

PMID- 19759238
TI  - Novel circular DNA viruses in stool samples of wild-living chimpanzees.
AB  - Viral particles in stool samples from wild-living chimpanzees were analysed using
      random PCR amplification and sequencing. Sequences encoding proteins distantly
      related to the replicase protein of single-stranded circular DNA viruses were
      identified. Inverse PCR was used to amplify and sequence multiple small circular
      DNA viral genomes. The viral genomes were related in size and genome organization
      to vertebrate circoviruses and plant geminiviruses but with a different location
      for the stem-loop structure involved in rolling circle DNA replication. The
      replicase genes of these viruses were most closely related to those of the much
      smaller (approximately 1 kb) plant nanovirus circular DNA chromosomes. Because
      the viruses have characteristics of both animal and plant viruses, we named them
      chimpanzee stool-associated circular viruses (ChiSCV). Further metagenomic
      studies of animal samples will greatly increase our knowledge of viral diversity
      and evolution.

PMID- 19759239
TI  - Comprehensive full-length sequence analyses of human parechoviruses: diversity
      and recombination.
AB  - Human parechoviruses (HPeVs) are highly prevalent pathogens among very young
      children. Although originally classified into two serologically distinct types,
      HPeV1 and -2, recent analyses of variants collected worldwide have revealed the
      existence of 12 further types classified genetically by sequence comparisons of
      complete genome sequences or the capsid (VP1) gene. To investigate the nature of
      HPeV evolution, its population dynamics and recombination breakpoints, this study
      generated 18 full-length genomic sequences of the most commonly circulating
      genotypes, HPeV1 and -3, collected over a time span of 14 years from The
      Netherlands. By inclusion of previously published full-length sequences, 35
      sequences were analysed in total. Analysis of contemporary strains of HPeV1 and
      those most similar to the prototype strain (Harris) showed that HPeV1 variants
      fall into two genetically distinct clusters that are much more divergent from
      each other than those observed within other HPeV types. Future classification
      criteria for HPeVs may require modification to accommodate the occurrence of
      variants with intermediate degrees of diversity within types. Recombination was
      frequently observed among HPeV1, -4, -5 and -6, but was much more restricted
      among HPeV3 strains. Favoured sites for recombination were found to flank the
      capsid region, and further sites were found within the non-structural region, P2.
      In contrast to other HPeV types, the majority of the HPeV3 sequences remained
      monophyletic across the genome, a possible reflection of its lower diversity and
      potentially more recent emergence than other HPeV types, or biological and/or
      epidemiological constraints that limit opportunities for co-infections with
      potential recombination partners.

PMID- 19759240
TI  - Characterization of phylogenetically diverse astroviruses of marine mammals.
AB  - Astroviruses are small, non-enveloped, positive-stranded RNA viruses. Previously
      studied mammalian astroviruses have been associated with diarrhoeal disease.
      Knowledge of astrovirus diversity is very limited, with only six officially
      recognized astrovirus species from mammalian hosts and, in addition, one human
      and some bat astroviruses were recently described. We used consensus PCR
      techniques for initial identification of five astroviruses of marine mammals:
      three from California sea lions (Zalophus californianus), one from a Steller sea
      lion (Eumetopias jubatus) and one from a bottlenose dolphin (Tursiops truncatus).
      Bayesian and maximum-likelihood phylogenetic analysis found that these viruses
      showed significant diversity at a level consistent with novel species.
      Astroviruses that we identified from marine mammals were found across the
      mamastrovirus tree and did not form a monophyletic group. Recombination analysis
      found that a recombination event may have occurred between a human and a
      California sea lion astrovirus, suggesting that both lineages may have been
      capable of infecting the same host at one point. The diversity found amongst
      marine mammal astroviruses and their similarity to terrestrial astroviruses
      suggests that the marine environment plays an important role in astrovirus
      ecology.

PMID- 19759241
TI  - Sequence diversity, population genetics and potential recombination events in
      grapevine rupestris stem pitting-associated virus in Pacific North-West
      vineyards.
AB  - Grapevine rupestris stem pitting-associated virus (GRSPaV; genus Foveavirus,
      family Flexiviridae) is present in many grape-growing regions of the world. A
      total of 84 full-length coat protein (CP) sequences and 57 sequences representing
      the helicase-encoding region (HR) of the RNA-dependent RNA polymerase were
      obtained from wine grape cultivars grown in the Pacific North-West (PNW) of the
      United States and their molecular diversity was compared with corresponding
      sequences previously reported from other grape-growing regions. In pairwise
      comparisons, the CP sequences from PNW isolates showed identities between 80 and
      100% at the nucleotide level and the HR sequences showed identities between 79
      and 100%. A global phylogenetic analysis of the CP and HR sequences revealed
      segregation of GRSPaV isolates into four major lineages with isolates from PNW
      distributed in all four lineages, indicating a lack of clustering by geographical
      origin. Scion cultivars grafted onto rootstock were found to contain mixtures of
      more genetic variants belonging to different lineages than own-rooted cultivars.
      Assessment of population genetic parameters found that the CP was more variable
      than the HR region. The discordant gene phylogenies obtained for some CP and HR
      sequences and the identification of potential recombination events involving
      parents from different lineages provided strong evolutionary evidence for genetic
      diversity among GRSPaV isolates. These results underscore the highly variable
      nature of the virus with implications for grapevine health status and
      distribution of virus-tested planting materials. This study also contributes to
      an increased understanding of molecular population genetics of viruses infecting
      deciduous woody perennials.

PMID- 19759242
TI  - The genetic backbone modulates the phenotype of hepatitis B surface antigen
      mutants.
AB  - Hepatitis B virus (HBV) vaccine and diagnostic escape mutants are a growing
      concern. The principle target of detection, hepatitis B surface antigen (HBsAg),
      encoded by S, is completely overlapped by the reverse transcriptase encoding P.
      With the increased incidence of nucleos(t)ide analogue resistance altering P, the
      concurrent impact on S must be assessed. HBV DNA from 59 HBsAg-positive plasma
      samples was sequenced across the polymerase/surface region and the amino acid
      sequence of HBsAg was inferred. ELISAs were formatted containing individually
      bound monoclonal antibodies directed against three discrete epitopes on HBsAg.
      Similar point mutations occurring in different genotypes were shown to influence
      epitope conformation differently, indicating that the genetic backbone is a major
      factor in predicting phenotype. C-terminal changes associated with antiviral
      resistance were found to modulate epitope profiles of HBsAg. Treatment options
      which may promote drug resistance should be avoided to both protect antiviral
      treatment and prevent facilitation of vaccine and diagnostic escape mutants.

PMID- 19759243
TI  - Trans-11 vaccenic acid reduces hepatic lipogenesis and chylomicron secretion in
      JCR:LA-cp rats.
AB  - Trans-11 vaccenic acid (VA) is the predominant trans isomer in ruminant fat and a
      major precursor to the endogenous synthesis of cis9,trans11-conjugated linoleic
      acid in humans and animals. We have previously shown that 3-wk VA supplementation
      has a triglyceride (TG)-lowering effect in a rat model of dyslipidemia, obesity,
      and metabolic syndrome (JCR:LA-cp rats). The objective of this study was to
      assess the chronic effect (16 wk) of VA on lipid homeostasis in both the liver
      and intestine in obese JCR:LA-cp rats. Plasma TG (P < 0.001), total cholesterol
      (P < 0.001), LDL cholesterol (P < 0.01), and nonesterified fatty acid
      concentrations, as well as the serum haptoglobin concentration, were all lower in
      obese rats fed the VA diet compared with obese controls (P < 0.05). In addition,
      there was a decrease in the postprandial plasma apolipoprotein (apo)B48 area
      under the curve (P < 0.05) for VA-treated obese rats compared with obese
      controls. The hepatic TG concentration and the relative abundance of fatty acid
      synthase and acetyl-CoA carboxylase proteins were all lower (P < 0.05) in the VA
      treated group compared with obese controls. Following acute gastrointestinal
      infusion of a VA-triolein emulsion in obese rats that had been fed the control
      diet for 3 wk, the TG concentration was reduced by 40% (P < 0.05) and the number
      of chylomicron (CM) particles (apoB48) in nascent mesenteric lymph was reduced by
      30% (P < 0.01) relative to rats infused with a triolein emulsion alone. In
      conclusion, chronic VA supplementation significantly improved dyslipidemia in
      both the food-deprived and postprandial state in JCR:LA-cp rats. The appreciable
      hypolipidemic benefits of VA may be attributed to a reduction in both intestinal
      CM and hepatic de novo lipogenesis pathways.

PMID- 19759244
TI  - Maternal milk, but not formula, regulates the immune response to beta
      lactoglobulin in allergy-prone rat pups.
AB  - Controversy exists regarding the timing of the introduction of allergic foods
      into the diet. We investigated the immune response of rat pups exposed to beta
      lactoglobulin (BLG), one of the main allergenic proteins in cow milk. Brown
      Norway allergy-prone rats were allocated into groups: dam-reared and unchallenged
      (DR), DR challenged with BLG via gavage (11 mg/d), or rats fed via gastric
      cannula a formula containing BLG (11 mg/d). BLG was given from d 4 of life. Rats
      were killed at d 10, 14, or 21. Sera were assayed for total IgE, BLG-specific
      IgG1, and rat mucosal mast cell protease II (RMCPII; indicator of mucosal mast
      cell degranulation). Ileum was assessed for cytokine mRNA. Mesenteric lymph nodes
      (MLN) were assessed for forkhead boxP3 (Foxp3) and chemokine (C-C motif) receptor
      7 (CCR7) expression by real-time PCR and immunostained for Foxp3(+) CD4(+)
      regulatory cells. Formula feeding compared with dam-rearing with or without oral
      BLG challenge resulted in significantly greater serum IgE, BLG-specific IgG1,
      RMCPII, and intestinal mast cells but reduced MLN Foxp3(+) cells, Foxp3, and CCR7
      expression and ileal cytokines, interleukin (IL)-4, IL-10, and interferon-gamma
      (P < 0.05). Importantly, giving BLG in the presence of maternal milk resulted in
      an immune response profile similar to that of unchallenged DR rats but with
      greater Foxp3 and CCR7 mRNA expression and CD4(+) Foxp3(+) cells (P < 0.05). We
      conclude that introducing an allergenic food with breast milk reduces
      immunological indicators of an allergic response, whereas introduction during
      formula feeding generates an allergic response.

PMID- 19759245
TI  - 1,2-vinyldithiin from garlic inhibits differentiation and inflammation of human
      preadipocytes.
AB  - Obesity is a state of chronic low-grade inflammation. Limiting white adipose
      tissue (WAT) expansion and therefore reducing inflammation could be effective in
      preventing the progression of obesity and the development of associated
      complications. We investigated the effects of 1,2-vinyldithiin (1,2-DT), a garlic
      derived organosulfur, on the differentiation and inflammatory state of human
      preadipocytes. Preadipocytes were prepared from subcutaneous adipose tissue of
      nonobese young women and differentiated in the presence of 1,2-DT. Inflammatory
      preadipocytes were obtained following treatment with human macrophage-secreted
      factors. 1,2-DT (100 micromol/L) significantly reduced gene expression of
      PPARgamma2 (-40%), CCAAT/enhancer binding protein-alpha (-25%), lipoprotein
      lipase (-22%), leptin (-30%), and adiponectin (-15%). Lipid accumulation was also
      significantly diminished in preadipocytes differentiated in the presence of 100
      micromol/L 1,2-DT (-37%) compared with controls. Furthermore, 100 micromol/L 1,2
      DT treatment for 10 d significantly reduced PPARgamma activity (-27%). The
      protein expression of perilipin and the secretion levels for 2 adipokines, leptin
      and adiponectin, were significantly diminished in 1,2-DT-cultured preadipocytes (
      37, -51, and -43%, respectively). Moreover, the secretion of inflammatory
      molecules (interleukin-6 and monocyte chemoattractant protein-1) induced by
      macrophage-secreted factors was partially abolished in 100 micromol/L 1,2-DT
      treated preadipocytes (-28 and -25%, respectively). In conclusion, we
      demonstrated that 1,2-DT, a garlic-derived organosulfur, has antiadipogenic and
      antiinflammatory actions on human preadipocytes and may be a novel, antiobesity
      nutraceutical.

PMID- 19759246
TI  - Feeding acutely stimulates fibrinogen synthesis in healthy young and elderly
      adults.
AB  - Fibrinogen is a positive acute-phase protein and its hepatic synthesis is
      enhanced following inflammation and injury. However, it is not clear whether
      fibrinogen synthesis is also responsive to oral nutrients and whether the
      response to a meal may be affected by age. Our aim in this study was to
      investigate the acute effect of oral feeding on fibrinogen synthesis in both
      young and elderly men and women. Fibrinogen synthesis was determined in 3
      separate occasions from the incorporation of l[(2)H(5)]phenylalanine (43 mg/kg
      body weight) in 8 young (21-35 y) and 8 elderly (>60 y) participants following
      the ingestion of water (control), a complete liquid meal (15% protein, 30% fat,
      and 55% carbohydrate), or only the protein component of the meal. The ingestion
      of the complete meal enhanced fibrinogen fractional synthesis rates (FSR) by 17
      +/- 6% in the young and by 38 +/- 10% in the elderly participants compared with
      the water meal (P < 0.02). A comparable stimulation of FSR occurred with only the
      protein component of the meal in both young (29 +/- 7%) and elderly participants
      (41 +/- 9%) compared with the water meal (P < 0.005). Similar results were
      obtained when fibrinogen synthesis was expressed as absolute synthesis rates
      (i.e. mg.kg(-1).d(-1)). The results demonstrate that fibrinogen synthesis is
      acutely stimulated after ingestion of a meal and that this effect can be
      reproduced by the protein component of the meal alone, both in young and elderly
      adults.

PMID- 19759247
TI  - Satiation due to equally palatable sweet and savory meals does not differ in
      normal weight young adults.
AB  - Sensory properties are greatly involved in the process of satiation. Regarding
      the nature of sensory signals, an important distinction can be made between sweet
      and savory taste. It is unclear, however, whether sweet and savory differ in
      their influence on satiation. Our objective was to investigate the difference
      between a sweet and savory taste on satiation, independent of palatability,
      texture, energy density, and macronutrient composition. A crossover design was
      used, consisting of 3 test conditions in which 2 tastes (sweet and savory) were
      compared. Sixty-four healthy, nonsmoking, unrestrained participants (18 males and
      46 females), with a mean age of 22.3 +/- 2.4 y and a mean BMI of 21.6 +/- 1.7
      kg/m(2), enrolled. Rice was used as a test meal served in either a sweet or
      savory version. The meals were similar in palatability, texture, energy density,
      and macronutrient composition. Ad libitum intake, eating rate, and changes in
      pleasantness and appetite during the meals were measured. Ad libitum intake did
      not differ between the 2 meals; participants ate a mean of 314 +/- 144 g of the
      sweet meal and 333 +/- 159 g of the savory meal. Eating rate (sweet, 38 +/- 14
      g/min; savory, 37 +/- 14 g/min) and changes in pleasantness and appetite during
      the meals were similar. Homogeneous meals with a sweet or savory taste, similar
      in palatability, texture, energy density, and macronutrient composition, do not
      differ in their influence on satiation in normal weight young adults.

PMID- 19759248
TI  - Western-style diets induce oxidative stress and dysregulate immune responses in
      the colon in a mouse model of sporadic colon cancer.
AB  - A Western-style diet (WD), defined by high-fat, low-calcium, and vitamin D
      content, is associated with increased risk of human colorectal cancer.
      Understanding molecular mechanisms altered by the WD is crucial to develop
      preventive and therapeutic strategies. Effects of a WD on the colonic
      transcriptome of C57Bl/6J mice, a model for sporadic colon cancer, were studied
      at endpoints before tumors occur. To assess whether a WD induces inflammatory
      changes, expression profiles of a broad spectrum of inflammatory proteins were
      performed and numbers of lamina propria macrophages were determined with
      semiquantitative morphometry. Transcriptome changes were translated into
      molecular interaction network maps and pathways. Pathways related to oxidative
      stress response; lipid, glutathione, and xenobiotic metabolism; and the immune
      response were perturbed by the WD. Several nuclear factor-erythroid 2-related
      factor 2- and aryl hydrocarbon receptor-dependent genes, including those coding
      for enzymes involved in phase 1 and 2 drug metabolism and oxidative stress
      responses, were induced. Oxidative stress was demonstrated by measurements of
      endogenous colonic redox-sensitive compound concentrations. Perturbations in
      immune response-related pathways, expression of inflammatory proteins, and
      increased numbers of lamina propria macrophages showed that the WD significantly
      alters the local colonic immune response. Collectively, these data suggest that
      consumption of a WD interferes with networks of related biological response
      pathways involving colonic lipid metabolism, oxidative stress, and the immune
      response. These new findings impact our understanding of links between
      consumption of WD and colon carcinogenesis, providing additional information for
      developing preventive means for decreasing colorectal cancer risk.

PMID- 19759249
TI  - A high mixed protein diet reduces body fat without altering the mechanical
      properties of bone in female rats.
AB  - Long-term consumption of high-protein (HP) diets at 35% of energy is postulated
      to negatively influence bone health. Previous studies have not comprehensively
      examined the biochemical, physical, and biomechanical properties of bone required
      to arrive at this conclusion. Our objective in this study was to examine the long
      term effect of a HP diet on bone metabolism, mass, and strength in rats. Adult
      female Sprague-Dawley rats (n = 80) were randomized to receive for 4, 8, 12, or
      17 mo a normal-protein (NP) control diet (15% of energy) or a HP diet (35% of
      energy). Diets were balanced for calcium because the protein sources were rich in
      calcium. At each time point, measurements included weight, body composition, and
      bone mass using dual-energy X-ray absorptiometry, mechanical strength at the mid
      diaphysis of femur and tibia, microarchitecture of femurs using microcomputerized
      tomography and serum osteocalcin, carboxy-terminal crosslinks of type I collagen
      (CTX), insulin-like growth factor-1 (IGF-1), leptin, and adiponectin. Effects of
      diet, time, and their interaction were tested using factorial ANOVA. The HP diet
      resulted in lower body weight, total body, and abdominal fat and higher lean
      mass. Serum leptin and adiponectin were greater in HP-fed than in NP-fed rats,
      but IGF-1 did not differ between the groups. Whereas the HP diet resulted in
      higher relative bone mineral content (g/kg) in the femur, tibia, and vertebrae,
      serum osteocalcin and CTX and bone internal architecture and biomechanical
      strength were unaffected. In conclusion, HP diets at 35% of energy lower body fat
      content without hindering the mechanical and weight-bearing properties of bone.

PMID- 19759250
TI  - Recombinant Sindbis virus vectors designed to express protective antigen of
      Bacillus anthracis protect animals from anthrax and display synergy with
      ciprofloxacin.
AB  - Recombinant Sindbis viruses were engineered to express alternative forms of the
      protective antigen (PA) of Bacillus anthracis. The recombinant viruses induced PA
      specific immunoglobulin G and neutralizing antibodies in Swiss Webster mice.
      Vaccination with the recombinant viruses induced immunity that offered some
      protection from a lethal Ames strain spore challenge and synergized the
      protective effects of ciprofloxacin.

PMID- 19759251
TI  - A novel 5-lipoxygenase-activating protein inhibitor, AM679, reduces inflammation
      in the respiratory syncytial virus-infected mouse eye.
AB  - Respiratory syncytial virus (RSV) is an important cause of viral respiratory
      disease in children, and RSV bronchiolitis has been associated with the
      development of asthma in childhood. RSV spreads from the eye and nose to the
      human respiratory tract. Correlative studies of humans and direct infection
      studies of BALB/c mice have established the eye as a significant pathway of entry
      of RSV to the lung. At the same time, RSV infection of the eye produces symptoms
      resembling allergic conjunctivitis. Cysteinyl leukotrienes (CysLTs) are known
      promoters of allergy and inflammation, and the first step in their biogenesis
      from arachidonic acid is catalyzed by 5-lipoxygenase (5-LO) in concert with the 5
      LO-activating protein (FLAP). We have recently developed a novel compound, AM679,
      which is a topically applied and potent inhibitor of FLAP. Here we show with the
      BALB/c mouse eye RSV infection model that AM679 markedly reduced the RSV-driven
      ocular pathology as well as the synthesis of CysLTs in the eye. In addition,
      AM679 decreased the production of the Th2 cell cytokine interleukin-4 but did not
      increase the viral load in the eye or the lung. These results suggest that FLAP
      inhibitors may be therapeutic for RSV-driven eye disease and possibly other
      inflammatory eye indications.

PMID- 19759252
TI  - Human immune proteome in experimental colonization with Staphylococcus aureus.
AB  - More than 20% of adults are persistently colonized with Staphylococcus aureus.
      When hospitalized, these carriers have increased risks of infection with their
      own strains. However, a recent study demonstrated a lower incidence of bacteremia
      related death among carriers than among noncarriers, raising the question whether
      the adaptive immune system plays a protective role. In fact, S. aureus carriers
      mount a highly specific neutralizing antibody response against superantigens of
      their colonizing strains. We now used 2-dimensional immunoblotting to investigate
      the profiles of antibodies from healthy individuals against S. aureus
      extracellular proteins. Moreover, we tested whether symptom-free experimental
      colonization of these individuals with an S. aureus strain of low virulence, 8325
      4, is sufficient to induce an antibody response. Sera obtained before and 4 weeks
      after colonization were screened for immunoglobulin G (IgG) antibody binding to
      extracellular staphylococcal proteins. At baseline, most volunteers harbored IgG
      directed against conserved virulence factors, including alpha-hemolysin (Hla),
      beta-hemolysin (Hlb), phospholipase C (Plc), staphylococcal serine protease
      (SspA), and cysteine protease (SspB). However, the variability of spot patterns
      and intensities was striking and could be important in case of infection.
      Experimental nasal colonization with S. aureus 8325-4 did not elicit new
      antibodies or boost the humoral response. Thus, the high antibody prevalence in
      humans is likely not induced by short-term nasal colonization, and presumably
      minor infections are required to trigger anti-S. aureus antibody responses.

PMID- 19759253
TI  - The role of caregiver prosody in conversations with persons who have Alzheimer's
      disease.
AB  - This research was supported in part by funding from the British Columbia Medical
      Services Foundation (BCM02-0115). The funding source had no role in the design,
      methods, participant recruitment, data collection, interpretation of the study,
      or in the preparation of the manuscript for publication. Approval for the study
      was granted by the University of British Columbia Behavioural Ethics Review
      Board, and participants provided informed consent. This study investigated
      whether aspects of family caregivers' prosody (pitch and loudness) would be
      associated with successful or unsuccessful conversations with spouses who have
      Alzheimer's disease (AD). Secondary analysis was conducted of 12 caregivers'
      speech when interacting with spouses who have AD. Acoustic analyses were
      conducted to calculate the fundamental frequency (pitch) and intensity (loudness)
      of caregivers' speech. The results showed no significant overall differences
      between the caregivers' pitch or loudness in either successful or unsuccessful
      conversations. However, for 1 subgroup of caregivers, an increase in pitch
      variation and loudness was associated with unsuccessful communication, whereas
      for another subgroup the opposite pattern was observed-reduced pitch variation
      and loudness with unsuccessful communication. The results provide preliminary
      directions for helping family caregivers become aware of how characteristics of
      their speech prosody may relate to the quality of communication when interacting
      with persons who have AD.

PMID- 19759254
TI  - Longitudinal verbal fluency in normal aging, preclinical, and prevalent
      Alzheimer's disease.
AB  - BACKGROUND: Few longitudinal studies evaluate differences in patterns of change
      of category compared to letter fluency across the spectrum of cognitive
      impairment. METHODS: We compared change in category (animal and supermarket) and
      letter (F, A, S) fluency among 239 participants in 3 groups: remained cognitively
      normal throughout follow-up (n = 96), developed Alzheimer's Disease (AD;
      preclinical AD, n = 21), and with AD at initial testing (prevalent AD, n = 122).
      RESULTS: At baseline, prevalent and preclinical AD groups scored lower on animal
      than letter fluency. On all fluency measures, the prevalent AD declined faster
      than other groups (all P < .0001), and preclinical AD declined faster than
      unimpaired (all P <or= .02). Overall, animal fluency declined faster than letter
      fluency; animal fluency declined significantly faster than letter fluency among
      cognitively normal and prevalent AD participants. CONCLUSION: Greater
      longitudinal declines in category compared to letter fluency are consistent with
      cross-sectional studies. Steeper declines on both fluency measures distinguish
      preclinical AD from cognitively unimpaired individuals.

PMID- 19759255
TI  - HIV-infected Thais need help to adjust to a normal life in society.

PMID- 19759256
TI  - Comparison of 3-drug versus 4-drug and PI versus non-PI combinations as initial
      HAART: experience from 1998 to 2007.
AB  - Although established in controlled studies that there is no advantage to 4-drug
      highly active antiretroviral therapy (HAART) or regimens with or without protease
      inhibitors (PIs), we questioned this finding in a clinical setting (ie, no
      inclusion criteria). Ours is a single clinic retrospective study including all
      participants >18 years of age during their first year of HAART. A total of 190
      participants were reviewed, with 168 (88%) attaining a viral load <400 copies/mL
      at the end of a year of HAART; 144 of 164 (88%) succeeded with 3 drugs and 24 of
      26 (92%) with 4 drugs (P = .51). In all, 59 of 71 (83%) succeeded using a PI
      versus 109 of 119 (92%) without a PI (P = .08). Male gender and exposure time to
      HAART were significant variables for a successful outcome. Failures were due to
      side effects (50%), nonadherence (45%), and drug allergy (5%). Our results
      support current guidelines recommending 3-drug HAART.

PMID- 19759257
TI  - First HAART in HIV-infected patients with high viral load: value of HIV RNA
      levels at 12 weeks to predict virologic outcome.
AB  - The aim of this study is to identify the role of incomplete suppression during
      the first months of highly active antiretroviral treatment (HAART) to predict
      virologic failure in patients with high levels of HIV replication. In a
      retrospective, longitudinal, and multicenter study, response to HAART was
      assessed in treatment-naive adults with HIV RNA >100 000 copies/mL, and factors
      predicting failure were analyzed through regression analyses. A total of 118
      patients were included. Virologic failure occurred more often in patients with
      >500 copies/mL at week 12 (Cox regression: Exp (B) 3.22; P = .02). HIV RNA >500
      copies/mL at week 12 predicted incomplete virologic response (odds ratio [OR] =
      9.33; P = .002] but not viral rebound. Major antiretroviral resistant mutations
      were present in 11 of 14 patients. HIV RNA >500 copies/mL at week 12 of first
      HAART predicts incomplete virologic response in patients with high levels of
      replication at baseline. Most patients carried resistance mutations at the time
      of failure.

PMID- 19759258
TI  - Association between age and the initiation of antihypertensive, lipid lowering
      and antiplateletet medications in elderly individuals newly treated with
      antidiabetic drugs.

PMID- 19759259
TI  - Delirium and long haul travel.

PMID- 19759260
TI  - Breaking down bone: new insight into site-specific mechanisms of breast cancer
      osteolysis mediated by metalloproteinases.
AB  - Bone metastases are the most common skeletal complication of malignancy. Tumor
      cells disrupt normal bone remodeling to promote bone destruction and its
      associated morbidity. In the August 15, 2009, issue of Genes & Development, Lu
      and colleagues (pp. 1882-1894) propose a novel molecular mechanism by which tumor
      produced metalloproteinases release epidermal growth factor (EGF) ligands to
      activate the central osteoclastogenic pathway receptor activator of NF-kappaB
      ligand (RANKL) to promote breast cancer osteolysis. This work has important
      therapeutic applications that may quickly translate to more effective treatment
      for bone metastases.

PMID- 19759261
TI  - Genomic imprinting: employing and avoiding epigenetic processes.
AB  - Genomic imprinting refers to an epigenetic mark that distinguishes parental
      alleles and results in a monoallelic, parental-specific expression pattern in
      mammals. Few phenomena in nature depend more on epigenetic mechanisms while at
      the same time evading them. The alleles of imprinted genes are marked
      epigenetically at discrete elements termed imprinting control regions (ICRs) with
      their parental origin in gametes through the use of DNA methylation, at the very
      least. Imprinted gene expression is subsequently maintained using noncoding RNAs,
      histone modifications, insulators, and higher-order chromatin structure.
      Avoidance is manifest when imprinted genes evade the genome-wide reprogramming
      that occurs after fertilization and remain marked with their parental origin.
      This review summarizes what is known about the establishment and maintenance of
      imprinting marks and discusses the mechanisms of imprinting in clusters.
      Additionally, the evolution of imprinted gene clusters is described. While
      considerable information regarding epigenetic control of imprinting has been
      obtained recently, much remains to be learned.

PMID- 19759262
TI  - Contextual extracellular cues promote tumor cell EMT and metastasis by regulating
      miR-200 family expression.
AB  - Metastatic disease is a primary cause of cancer-related death, and factors
      governing tumor cell metastasis have not been fully elucidated. Here, we address
      this question by using tumor cell lines derived from mice that develop metastatic
      lung adenocarcinoma owing to expression of mutant K-ras and p53. Despite having
      widespread somatic genetic alterations, the metastasis-prone tumor cells retained
      a marked plasticity. They transited reversibly between epithelial and mesenchymal
      states, forming highly polarized epithelial spheres in three-dimensional culture
      that underwent epithelial-to-mesenchymal transition (EMT) following treatment
      with transforming growth factor-beta or injection into syngeneic mice. This
      transition was entirely dependent on the microRNA (miR)-200 family, which
      decreased during EMT. Forced expression of miR-200 abrogated the capacity of
      these tumor cells to undergo EMT, invade, and metastasize, and conferred
      transcriptional features of metastasis-incompetent tumor cells. We conclude that
      tumor cell metastasis is regulated by miR-200 expression, which changes in
      response to contextual extracellular cues.

PMID- 19759263
TI  - MicroRNA dynamics in the stages of tumorigenesis correlate with hallmark
      capabilities of cancer.
AB  - While altered expression of microRNAs (miRs) in tumors has been well documented,
      it remains unclear how the miR transcriptome intersects neoplastic progression.
      By profiling the miR transcriptome we identified miR expression signatures
      associated with steps in tumorigenesis and the acquisition of hallmark
      capabilities in a prototypical mouse model of cancer. Metastases and a rare
      subset of primary tumors shared a distinct miR signature, implicating a discrete
      lineage for metastatic tumors. The miR-200 family is strongly down-regulated in
      metastases and met-like primary tumors, thereby relieving repression of the
      mesenchymal transcription factor Zeb1, which in turn suppresses E-cadherin.
      Treatment with a clinically approved angiogenesis inhibitor normalized angiogenic
      signature miRs in primary tumors, while altering expression of metastatic
      signature miRs similarly to liver metastases, suggesting their involvement in
      adaptive resistance to anti-angiogenic therapy via enhanced metastasis. Many of
      the miR changes associated with specific stages and hallmark capabilities in the
      mouse model are similarly altered in human tumors, including cognate pancreatic
      neuroendocrine tumors, implying a generality.

PMID- 19759264
TI  - Phosphorylation modulates rapid nucleocytoplasmic shuttling and cytoplasmic
      accumulation of Neurospora clock protein FRQ on a circadian time scale.
AB  - The Neurospora clock protein FREQUENCY (FRQ) is an essential regulator of the
      circadian transcription factor WHITE COLLAR COMPLEX (WCC). In the course of a
      circadian period, the subcellular distribution of FRQ shifts from mainly nuclear
      to mainly cytosolic. This shift is crucial for coordinating the negative and
      positive limbs of the clock. We show that the subcellular redistribution of FRQ
      on a circadian time scale is governed by rapid, noncircadian cycles of nuclear
      import and export. The rate of nuclear import of newly synthesized FRQ is
      progressively reduced in a phosphorylation-dependent manner, leading to an
      increase in the steady-state level of cytoplasmic FRQ. The long-period frq(7)
      mutant displays reduced kinetics of FRQ(7) protein phosphorylation and a
      prolonged accumulation in the nucleus. We present a mathematical model that
      describes the cytoplasmic accumulation of wild-type and mutant FRQ on a circadian
      time scale on the basis of frequency-modulated rapid nucleocytoplasmic shuttling
      cycles.

PMID- 19759265
TI  - TBP2 is essential for germ cell development by regulating transcription and
      chromatin condensation in the oocyte.
AB  - Development of the germline requires consecutive differentiation events.
      Regulation of these has been associated with germ cell-specific and pluripotency
      associated transcription factors, but the role of general transcription factors
      (GTFs) remains elusive. TATA-binding protein (TBP) is a GTF involved in
      transcription by all RNA polymerases. During ovarian folliculogenesis in mice the
      vertebrate-specific member of the TBP family, TBP2/TRF3, is expressed exclusively
      in oocytes. To determine TBP2 function in vivo, we generated TBP2-deficient mice.
      We found that Tbp2(-/-) mice are viable with no apparent phenotype. However,
      females lacking TBP2 are sterile due to defective folliculogenesis, altered
      chromatin organization, and transcriptional misregulation of key oocyte-specific
      genes. TBP2 binds to promoters of misregulated genes, suggesting that TBP2
      directly regulates their expression. In contrast, TBP ablation in the female
      germline results in normal ovulation and fertilization, indicating that in these
      cells TBP is dispensable. We demonstrate that TBP2 is essential for the
      differentiation of female germ cells, and show the mutually exclusive functions
      of these key core promoter-binding factors, TBP and TBP2, in the mouse.

PMID- 19759266
TI  - Ipl1/Aurora B kinase coordinates synaptonemal complex disassembly with cell cycle
      progression and crossover formation in budding yeast meiosis.
AB  - Several protein kinases collaborate to orchestrate and integrate cellular and
      chromosomal events at the G2/M transition in both mitotic and meiotic cells.
      During the G2/M transition in meiosis, this includes the completion of crossover
      recombination, spindle formation, and synaptonemal complex (SC) breakdown. We
      identified Ipl1/Aurora B kinase as the main regulator of SC disassembly. Mutants
      lacking Ipl1 or its kinase activity assemble SCs with normal timing, but fail to
      dissociate the central element component Zip1, as well as its binding partner,
      Smt3/SUMO, from chromosomes in a timely fashion. Moreover, lack of Ipl1 activity
      causes delayed SC disassembly in a cdc5 as well as a CDC5-inducible ndt80 mutant.
      Crossover levels in the ipl1 mutant are similar to those observed in wild type,
      indicating that full SC disassembly is not a prerequisite for joint molecule
      resolution and subsequent crossover formation. Moreover, expression of meiosis I
      and meiosis II-specific B-type cyclins occur normally in ipl1 mutants, despite
      delayed formation of anaphase I spindles. These observations suggest that Ipl1
      coordinates changes to meiotic chromosome structure with resolution of crossovers
      and cell cycle progression at the end of meiotic prophase.

PMID- 19759267
TI  - Renal salt wasting and chronic dehydration in claudin-7-deficient mice.
AB  - Claudin-7, a member of the claudin family, is highly expressed in distal nephrons
      of kidneys and has been reported to be involved in the regulation of paracellular
      Cl(-) permeability in cell cultures. To investigate the role of claudin-7 in
      vivo, we generated claudin-7 knockout mice (Cln7(-/-)) by the gene-targeting
      deletion method. Here we report that Cln7(-/-) mice were born viable, but died
      within 12 days after birth. Cln7(-/-) mice showed severe salt wasting, chronic
      dehydration, and growth retardation. We found that urine Na(+), Cl(-), and K(+)
      were significantly increased in Cln7(-/-) mice compared with that of Cln7(+/+)
      mice. Blood urea nitrogen and hematocrit were also significantly higher in Cln7(
      /-) mice. The wrinkled skin was evident when Cln7(-/-) mice were approximately 1
      wk old, indicating that they suffered from chronic fluid loss. Transepidermal
      water loss measurements showed no difference between Cln7(+/+) and Cln7(-/-)
      skin, suggesting that there was no transepidermal water barrier defect in Cln7(-/
      ) mice. Claudin-7 deletion resulted in the dramatic increase of aldosterone
      synthase mRNA level as early as 2 days after birth. The significant increases of
      epithelial Na(+) channel alpha, Na(+)-Cl(-) cotransporter, and aquaporin 2 mRNA
      levels revealed a compensatory response to the loss of electrolytes and fluid in
      Cln7(-/-) mice. Na(+)-K(+)-ATPase alpha(1) expression level was also greatly
      increased in distal convoluted tubules and collecting ducts where claudin-7 is
      normally expressed. Our study demonstrates that claudin-7 is essential for NaCl
      homeostasis in distal nephrons, and the paracellular ion transport pathway plays
      indispensable roles in keeping ionic balance in kidneys.

PMID- 19759268
TI  - Exercise activates redox-sensitive transcription factors and restores renal D1
      receptor function in old rats.
AB  - We have previously reported that age-associated oxidative stress via protein
      kinase C (PKC) increases D1 receptor (D1R) phosphorylation and causes D1R-G
      protein uncoupling in renal proximal tubules (RPTs) of old Fischer 344 rats. This
      results in reduced ability of D1R agonist SKF-38393 to inhibit Na+-K+-ATPase in
      RPTs of old rats. Here, we studied the effect of treadmill exercise on markers of
      oxidative stress, PKC, D1R phosphorylation, D1R-G protein coupling, and Na+-K+
      ATPase activity in RPTs of adult and old rats. We found increased levels of
      malondialdehyde, a marker of oxidative stress, in RPTs of old rats, which
      decreased during exercise. Nuclear levels of nuclear erythroid-related factor
      (Nrf)-2 and nuclear factor (NF)-kappaB in RPTs, transcription factors involved in
      antioxidant enzyme gene transcription, increased in exercised old rats. This was
      accompanied by an increase in the activity and expression of antioxidant enzymes,
      superoxide dismutase and heme oxygenase-1. Age-related decrease in the levels of
      D1R mRNAs and proteins was attenuated during exercise. Furthermore, exercise in
      old rats decreased PKC activity and D1R phosphorylation and increased SKF-38393
      mediated [35S]guanosine 5'-O-(3-thiotriphosphate) binding (an index of D1R-G
      protein coupling). SKF-38393 also caused inhibition of Na+-K+-ATPase in these
      animals. Also, exercise caused a decrease in proteinuria and increase in
      phosphaturia in old rats. These results suggest beneficial effects of exercise in
      terms of increasing antioxidant defenses, decreasing oxidative stress, and
      improving kidney function in general and D1R function in particular in aging.
      Both Nrf-2 and NF-kappaB seem to play key role in this phenomenon.

PMID- 19759269
TI  - Maternal nutrient restriction during early fetal kidney development attenuates
      the renal innate inflammatory response in obese young adult offspring.
AB  - Obesity is an independent risk factor for developing chronic kidney disease. Toll
      like receptor 4 (TLR4), interleukin (IL)-18, and uncoupling protein 2 (UCP2) are
      important components of the innate immune system mediating inflammatory renal
      damage. Early to midgestation maternal nutrient restriction appears to protect
      the kidney from the deleterious effects of early onset obesity, although the
      mechanisms remain unclear. We examined the combined effects of gestational
      maternal nutrient restriction during early fetal kidney development and early
      onset obesity on the renal innate immune response in offspring. Pregnant sheep
      were randomly assigned to a normal (control, 100%) or nutrient-restricted (NR,
      50%) diet from days 30 to 80 gestation and 100% thereafter. Offspring were killed
      humanely at 7 days or, following rearing in an obesogenic environment, at 1 yr of
      age, and renal tissues were collected. IL-18 and TLR4 expression were strongly
      correlated irrespective of intervention. Seven-day NR offspring had significantly
      lower relative renal mass and IL-18 mRNA expression. At 1 yr of age, obesity
      resulted in increased mRNA abundance of TLR4, IL-18, and UCP2, coupled with
      tubular atrophy and greater immunohistological staining of glomerular IL-6 and
      medullary tumor necrosis factor (TNF)-alpha. NR obese offspring had a marked
      reduction of TLR4 abundance and renal IL-6 staining. In conclusion, maternal
      nutrient restriction during early fetal kidney development attenuates the effects
      of early onset obesity-related nephropathy, in part, through the downregulation
      of the innate inflammatory response. A better understanding of maternal nutrition
      and the in utero nutritional environment may offer therapeutic strategies aimed
      at reducing the burden of later kidney disease.

PMID- 19759270
TI  - Is nephrogenesis affected by preterm birth? Studies in a non-human primate model.
AB  - Nephrogenesis occurs predominantly in late gestation at a time when preterm
      infants are already delivered. The aims of this study were to assess the effect
      of preterm birth and the effect of antenatal glucocorticoid treatment on
      nephrogenesis. Preterm baboons, which were delivered at 125 days gestation and
      ventilated for up to 21 days postnatally, were compared with gestational
      controls. A cohort of preterm baboons that had been exposed to antenatal
      glucocorticoids were compared with unexposed preterm baboons. The number of
      glomerular generations was estimated using a medullary ray glomerular-counting
      method, and glomerular number was estimated using unbiased stereology. CD31 and
      WT-1 localization was examined using immunohistochemistry and VEGF was localized
      using in situ hybridization. The number of glomerular generations was not
      affected by preterm birth, and total glomerular numbers were within the normal
      range. Kidneys were significantly enlarged in preterm baboons with a significant
      decrease in glomerular density (number of glomeruli per gram of kidney) in the
      preterm kidney compared with gestational controls. Neonates exposed to antenatal
      steroids had an increased kidney-to-body weight ratio and also more developed
      glomeruli compared with unexposed controls. Abnormal glomeruli, with a cystic
      Bowman's space and shrunken glomerular tuft, were often present in the
      superficial renal cortex of both the steroid-exposed and unexposed preterm
      kidneys; steroid exposure had no significant effect on the proportion of abnormal
      glomeruli. The proportion of abnormal glomeruli in the preterm kidneys ranged
      from 0.2 to 18%. In conclusion, although nephrogenesis is ongoing in the
      extrauterine environment, our findings demonstrate that preterm birth,
      independent of steroid exposure, is associated with a high proportion of abnormal
      glomeruli in some, but not all neonatal kidneys. Whether final nephron endowment
      is affected in those kidneys exhibiting a high proportion of abnormal glomeruli
      is yet to be confirmed.

PMID- 19759271
TI  - Bradykinin induces formation of vesicle-like structures containing vinculin and
      PtdIns(4,5)P2 in renal papillary collecting duct cells.
AB  - Focal adhesions (FAs) are structures of cell attachment to the extracellular
      matrix. We previously demonstrated that the intrarenal hormone bradykinin (BK)
      induces the restructuring of FAs in papillary collecting duct cells by
      dissipation of vinculin, but not talin, from FAs through a mechanism that
      involves PLCbeta activation, and that it also induces actin cytoskeleton
      reorganization. In the present study we investigated the mechanism by which BK
      induces the dissipation of vinculin-stained FAs in collecting duct cells. We
      found that BK induces the internalization of vinculin by a noncaveolar and
      independent pinocytic pathway and that at least a fraction of this protein is
      delivered to the recycling endosomal compartment, where it colocalizes with the
      transferrin receptor. Regarding the reassembly of vinculin-stained FAs, we found
      that BK induces the formation of phosphatidylinositol 4,5-bisphosphate
      [PtdIns(4,5)P2]-enriched vinculin-containing vesicles, which, by following a
      polarized exocytic route, transport vinculin to the site of FA assembly, an
      action that depends on actin filaments. The present study, which was carried out
      with cells that were not genetically manipulated, shows for the first time that
      BK induces the formation of vesicle-like structures containing vinculin and
      PtdIns(4,5)P2, which transport vinculin to the site of FA assembly. Therefore,
      the modulation of the formation of these vesicle-like structures could be a
      physiological mechanism through which the cell can reuse the BK-induced
      internalized vinculin to be delivered for newly forming FAs in renal papillary
      collecting duct cells.

PMID- 19759272
TI  - Impaired TGF-beta signalling enhances peritoneal inflammation induced by E. coli
      in rats.
AB  - BACKGROUND: Peritonitis is a common and severe complication of peritoneal
      dialysis (PD). Although TGF-beta is a key mediator in peritoneal fibrosis with
      chronic PD, its role in acute peritoneal inflammation remains unclear. METHODS:
      Potential role of TGF-beta signalling in acute peritonitis was investigated in a
      rat model by infecting peritoneum with E. coli and in primary culture of
      peritoneal mesothelial cells (PMC) by LPS. RESULTS: We found that a single
      infection of E. coli caused an acute, but transient peritonitis by a significant
      increase in ascites white blood cells (WBC), peritoneal CD45+ leukocytes,
      upregulation of TNFalpha, activation of NF-kappaB/p65 and impaired peritoneal
      function (all P < 0.01). Interestingly, spontaneous recovery of acute peritonitis
      occurred with upregulation of TGF-beta1 and activation of Smad2/3, suggesting a
      protective role of TGF-beta signalling in acute peritonitis. This was
      demonstrated by the finding that blockade of the TGF-beta signalling pathway with
      gene transfer of Smad7 inactivated peritoneal Smad2/3 but worsened E. coli
      induced, NF-kappaB-dependent peritoneal inflammation and peritoneal dysfunction
      (all P < 0.01). Furthermore, studies in vitro also found that impaired TGF-beta
      signalling by overexpressing Smad7 in PMC were able to overcome the inhibitory
      effect of TGF-beta on LPS-induced, NF-kappaB-mediated peritoneal inflammation.
      CONCLUSION: Results from this study demonstrate that TGF-beta signalling is
      essential in protection against acute peritoneal inflammation induced by
      bacterial infection.

PMID- 19759273
TI  - Effects of icodextrin peritoneal dialysis solution on the peritoneal membrane in
      the STZ-induced diabetic rat model with partial nephrectomy.
AB  - BACKGROUND: Application of icodextrin-based peritoneal dialysis fluid (PDF)
      provides a potential benefit in patients with diabetes and end-stage renal
      failure treated with continuous ambulatory peritoneal dialysis (CAPD) because of
      better ultrafiltration capacity and avoidance of direct glucose exposure. We
      examined the effect of glucose and icodextrin-based PDF on histological
      alterations of peritoneal membranes. METHODS: Thirty-two male Wistar rats were
      divided into four groups: control Wistar rats with non-treated (n = 8),
      streptozotocin (STZ)-induced diabetic rats with 5/6 kidney ablation (n = 8), STZ
      induced diabetic rats with 5/6 kidney ablation injected with a standard lactate
      buffered 4.25% glucose-based PDF (Dianeal; n = 8) and STZ-induced diabetic rats
      with 5/6 kidney ablation injected with 7.5% icodextrin-based PDF (Extraneal; n =
      8). Intraperitoneal injection was performed once daily with an instillation
      volume of 20 ml per injection during 8 weeks. RESULTS: Chronic high-glucose-based
      PDF exposure resulted in increased vascular endothelial growth factor (VEGF) and
      basic fibroblast growth factor (bFGF) expression, accumulation of advanced
      glycation end-products (AGEs), and up-regulation of the receptor for AGE (RAGE),
      which were ameliorated in the icodextrin-based PDF group. The peritoneal damages,
      such as neoangiogenesis and submesothelial fibrosis, were significantly reduced
      in icodextrin-based PDF compared to high-glucose-based PDF. CONCLUSIONS: Long
      term in vivo exposure to high glucose-based PDF promotes the fibrosing process of
      peritoneal membranes. Icodextrin-based PDF may be helpful in slowing the PDF
      induced deterioration of peritoneal function and prolonging the use of peritoneal
      dialysis in patients with diabetes.

PMID- 19759274
TI  - Current status of renal and urinary proteomics: ready for routine clinical
      application?

PMID- 19759275
TI  - Glycome-DB.org: a portal for querying across the digital world of carbohydrate
      sequences.
AB  - Despite ongoing harmonization efforts, the major carbohydrate sequence databases
      following the first initiative in this field, CarbBank, are still isolated
      islands, with mechanisms for automatic structure exchange and comparison largely
      missing. This unfavorable situation has been overcome with a systematic data
      integration effort, resulting in the GlycomeDB, a meta-database for public
      carbohydrate sequences. It contains at present 35,056 unique structures in
      GlycoCT encoding, referencing more than 100,000 external records from 1845
      different taxonomic sources. We have created a user-friendly, web-based graphical
      interface which allows taxonomic and structural data to be entered and searched
      for. The structural search possibilities include substructure search, similarity
      search, and maximum common substructure. A novel search refinement mechanism
      allows the assembly of complex queries. With GlycomeDB (www.glycome-db.org), it
      is now possible to use a single portal to access all digitally encoded, public
      structural data in glycomics and to perform complex queries with the help of a
      web-based user interface.

PMID- 19759276
TI  - Endomannosidase undergoes phosphorylation in the Golgi apparatus.
AB  - Glucose residues from N-linked oligosaccharides are removed by glucosidases I and
      II in the endoplasmic reticulum (ER) or by the alternate endomannosidase pathway
      in the Golgi apparatus. Our morphological analysis demonstrates that recombinant
      rat endomannosidase exhibited a cis- and medial-Golgi localization alike the
      endogenous enzyme and its ER to Golgi transport is COP II mediated. Recombinant
      endomannosidase undergoes a posttranslational modification, which is not related
      to N-or O-glycosylation. A shift in molecular mass of recombinant endomannosidase
      was observed upon phosphatase digestion but not for ER-retained CHO cell
      endomannosidase. Furthermore, immunoprecipitation of (35)S- and (33)P-labeled
      endomannosidase expressed in CHO-K1 cells suggests that recombinant
      endomannosidase undergoes phosphorylation. Substitution of the single cytoplasmic
      threonine residue of rat endomannosidase by either an alanine or valine residue
      resulted in the same posttranslational modification alike the wild-type enzyme.
      The subcellular localization and the in vivo activity of the mutant
      endomannosidase were not affected. Thus, endomannosidase phosphorylation is
      occurring in luminal sequences. Modification was prevented when endomannosidase
      was synthesized using reticulocyte lysates in the presence of canine microsomes.
      Treatment of cells with brefeldin A blocked the posttranslational modification of
      endomannosidase, suggesting that phosphorylation is occurring in the Golgi
      apparatus, the residence of endomannosidase.

PMID- 19759277
TI  - Impact of tryptophan metabolism on the vulnerability to alcohol-related blackouts
      and violent impulsive behaviours.
AB  - AIMS: We examined (1) the association of SLC6A4 genotypes and alcohol dependence
      (AD) in a sample of alcoholics; (2) the validity of lifetime occurrence of
      blacked-out violent impulsive behaviour (BOVIB) during binge drinking bouts as a
      criterion for subtyping AD patients and (3) a mechanistic hypothesis for BOVIB
      involving tryptophan-2,3-dioxygenase (TDO) activity. METHODS: Three common
      polymorphisms of the SLC6A4 gene (5-HTTLPR, A/G SNP of LPR region and VNTR in
      intron 2) were genotyped. An oral tryptophan (Trp) load (OTL) was administered to
      a sample of patients seeking help for AD. BOVIB history and psychological status
      were screened by BOVIB-Q, depression (BDI), anxiety (BAI, STAI) and personality
      (TCI) questionnaires. During the 7 h following Trp load, serum kynurenine (Kyn)
      and Trp were monitored. RESULTS: BOVIB+ patients showed significantly higher
      scores on depression, anxiety and character scales but no significant association
      was found between SLC6A4 polymorphisms and BOVIB. Patients with a history of
      BOVIB (BOVIB+ subgroup) differed from those exempt from such episodes (BOVIB-
      subgroup) for TDO activity response to OTL assessed by the Kyn:Trp ratio (P =
      0.043) and the slope of concentration increase ratio (SCIR) of serum Kyn (P =
      0.043). CONCLUSIONS: Put together, these findings support the validity of the
      BOVIB criterion to differentiate a sub-group of vulnerable AD subjects and
      suggest that OTL may help to concurrently define a specific endophenotype.

PMID- 19759278
TI  - Introduction to the special issue of Alcohol and Alcoholism on sex/gender
      differences in responses to alcohol.

PMID- 19759279
TI  - Sex differences in caffeine neurotoxicity following chronic ethanol exposure and
      withdrawal.
AB  - AIMS: Caffeine is a central nervous system stimulant that produces its primary
      effects via antagonism of the A(1) and A(2A) adenosine receptor subtypes.
      Previous work demonstrated a sex difference in neurotoxicity produced by specific
      adenosine A(1) receptor antagonism during ethanol withdrawal (EWD) in vitro that
      was attributable to effects downstream of A(1) receptors at NMDA receptors. The
      current studies were designed to examine the effect of non-specific adenosine
      receptor antagonism with caffeine during ethanol withdrawal on hippocampal
      toxicity in cultures derived from male and female rats. METHODS: At 5 days in
      vitro (DIV), half of the male and female organotypic hippocampal slice cultures
      were exposed to 50 mM ethanol (EtOH) in culture media for 10 days before exposure
      to caffeine (5, 20 and 100 microM) for the duration of a 24 h EWD period. In
      keeping with this timeline, the remaining ethanol-naive cultures were given media
      changes at 10 and 15 DIV and exposed to caffeine (5, 20 and 100 microM) for 24 h
      at 15 DIV. Cytotoxicity was assessed by fluorescent microscopy and quantification
      of propidium iodide (PI) uptake in the pyramidal cell layers of the CA1 and CA3
      regions and the granule cell layer of the dentate gyrus (DG). A two-way (sex x
      treatment) ANOVA was conducted within each hippocampal region. RESULTS: Twenty
      four-hour withdrawal from 10-day exposure to 50 mM ethanol did not produce
      increased PI uptake in any hippocampal region. Caffeine exposure (5, 20 and 100
      microM) in ethanol-naive cultures did not produce toxicity in the DG or CA1
      region, but 20 microM caffeine produced modest toxicity in the CA3 region.
      Exposure to 20 microM caffeine during EWD produced cytotoxicity in all
      hippocampal regions, though toxicity was sex-dependent in the DG and CA1 region.
      In the DG, both 5 and 20 microM caffeine produced significantly greater PI uptake
      in ethanol-exposed female cultures compared to ethanol-naive female cultures and
      all male cultures. Similarly, 20 microM caffeine caused markedly greater toxicity
      in female cultures as compared to male cultures in the CA1 region. CONCLUSIONS:
      Twenty-four-hour exposure to caffeine during EWD produced significant toxicity in
      the pyramidal cell layer of the CA3 region in male and female cultures, though
      toxicity in the granule cell layer of the DG and pyramidal cell layer of the CA1
      region was observed only in female cultures. Greater sensitivity of the female
      slice cultures to toxicity upon caffeine exposure after prolonged ethanol
      exposure is consistent with previous studies of effects of a specific A(1)
      receptor antagonism during EWD on toxicity and indicate that this effect is
      independent of the hormonal milieu. Together, these data suggest that the A(1)
      receptor subtype is predominant in mediating caffeine's neurotoxic effects during
      EWD. These findings demonstrate the importance of considering gender/sex when
      examining neuroadaptive changes in response to ethanol exposure and withdrawal.

PMID- 19759280
TI  - The axonal repellent, Slit2, inhibits directional migration of circulating
      neutrophils.
AB  - In inflammatory diseases, circulating neutrophils are recruited to sites of
      injury. Attractant signals are provided by many different chemotactic molecules,
      such that blockade of one may not prevent neutrophil recruitment effectively. The
      Slit family of secreted proteins and their transmembrane receptor, Robo, repel
      axonal migration during CNS development. Emerging evidence shows that by
      inhibiting the activation of Rho-family GTPases, Slit2/Robo also inhibit
      migration of other cell types toward a variety of chemotactic factors in vitro
      and in vivo. The role of Slit2 in inflammation, however, has been largely
      unexplored. We isolated primary neutrophils from human peripheral blood and mouse
      bone marrow and detected Robo-1 expression. Using video-microscopic live cell
      tracking, we found that Slit2 selectively impaired directional migration but not
      random movement of neutrophils toward fMLP. Slit2 also inhibited neutrophil
      migration toward other chemoattractants, namely C5a and IL-8. Slit2 inhibited
      neutrophil chemotaxis by preventing chemoattractant-induced actin barbed end
      formation and cell polarization. Slit2 mediated these effects by suppressing
      inducible activation of Cdc42 and Rac2 but did not impair activation of other
      major kinase pathways involved in neutrophil migration. We further tested the
      effects of Slit2 in vivo using mouse models of peritoneal inflammation induced by
      sodium periodate, C5a, and MIP-2. In all instances, Slit2 reduced neutrophil
      recruitment effectively (P<0.01). Collectively, these data demonstrate that Slit2
      potently inhibits chemotaxis but not random motion of circulating neutrophils and
      point to Slit2 as a potential new therapeutic for preventing localized
      inflammation.

PMID- 19759281
TI  - Modulation of human plasmacytoid DC function by IFN-lambda1 (IL-29).
AB  - The type III family of IFNs displays immunomodulatory and antiviral activity.
      Each member (IFN-lambda1, -2, and -3) signals through the same heterodimeric
      receptor complex, which consists of the binding and signaling subunit (IL
      28Ralpha) plus the IL-10Rbeta chain. Although the receptor has a wide tissue
      distribution, the direct effects of IFN-lambda on various immune cell subsets
      have not been fully characterized. We have identified high levels of IL-28Ralpha
      mRNA in pDC from peripheral blood and hypothesized that IFN-lambda plays an
      important role in pDC maturation and development. We show that stimulation of pDC
      with HSV or Imiquimod causes an increase in IL-28Ralpha mRNA. In these cells, IFN
      lambda1 alters expression of the costimulatory molecules CD80 and ICOS-L and
      synergizes with IFN-alpha to up-regulate CD83. In addition, IFN-lambda1 has a
      variable effect on the homing molecule expression of pDC and mDC. IFN-lambda1
      treated pDC display a marked difference in their ability to stimulate production
      of the signature cytokines IL-13, IFN-gamma, and IL-10 in a MLR. This work
      characterizes the variable effects of IFN-lambda on DC surface molecule
      expression and identifies a role in pDC activation and immunostimulatory
      potential.

PMID- 19759282
TI  - Dynamins at a glance.

PMID- 19759283
TI  - Internalization and intracellular sorting of the EGF receptor: a model for
      understanding the mechanisms of receptor trafficking.
AB  - The epidermal growth factor receptor (EGFR; also known as ErbB1) is one of four
      related receptor tyrosine kinases. These receptors (EGFR, ErbB2, ErbB3 and ErbB4)
      are frequently overexpressed in cancer and such overexpression is associated with
      poor clinical outcome. Understanding the mechanisms involved in growth-factor
      receptor downregulation is medically important, as several drugs that interfere
      with the function and trafficking of ErbB proteins are currently being developed
      or are already in clinical trials. EGFR has become a model protein for
      understanding the biology and endocytosis of related growth-factor receptors, and
      the mechanisms involved in its endocytosis and degradation have been scrutinized
      for several decades. Nevertheless, the details and principles of these processes
      are still poorly understood and often controversial. In particular, the
      literature describing how the ubiquitylation and recruitment of EGFR to clathrin
      coated pits are connected is inconsistent and confusing. In this Opinion article,
      we discuss the impact of signaling motifs, kinase activity and ubiquitylation on
      clathrin-dependent endocytosis and lysosomal sorting of EGFR. In addition, we
      discuss potential explanations for contradicting reports, and propose models for
      the recruitment of ligand-activated EGFR to clathrin-coated pits as well as for
      lysosomal sorting of ligand-activated EGFR.

PMID- 19759285
TI  - Variations in the requirement for v-SNAREs in GLUT4 trafficking in adipocytes.
AB  - Vesicle transport in eukaryotic cells is regulated by SNARE proteins, which play
      an intimate role in regulating the specificity of vesicle fusion between discrete
      intracellular organelles. In the present study we investigated the function and
      plasticity of v-SNAREs in insulin-regulated GLUT4 trafficking in adipocytes.
      Using a combination of knockout mice, v-SNARE cleavage by clostridial toxins and
      total internal reflection fluorescence microscopy, we interrogated the function
      of VAMPs 2, 3 and 8 in this process. Our studies reveal that the simultaneous
      disruption of VAMPs 2, 3 and 8 completely inhibited insulin-stimulated GLUT4
      insertion into the plasma membrane, due to a block in vesicle docking at the
      plasma membrane. These defects could be rescued by re-expression of VAMP2, VAMP3
      or VAMP8 alone, but not VAMP7. These data indicate a plasticity in the
      requirement for v-SNAREs in GLUT4 trafficking to the plasma membrane and further
      define an important role for the v-SNARE proteins in pre-fusion docking of
      vesicles.

PMID- 19759284
TI  - Regulation of cell migration and morphogenesis by Abl-family kinases: emerging
      mechanisms and physiological contexts.
AB  - The Abl-family non-receptor tyrosine kinases are essential regulators of the
      cytoskeleton. They transduce diverse extracellular cues into cytoskeletal
      rearrangements that have dramatic effects on cell motility and morphogenesis.
      Recent biochemical and genetic studies have revealed several mechanisms that Abl
      family kinases use to mediate these effects. Abl-family kinases stimulate actin
      polymerization through the activation of cortactin, hematopoietic lineage cell
      specific protein (HS1), WASp- and WAVE-family proteins, and Rac1. They also
      attenuate cell contractility by inhibiting RhoA and altering adhesion dynamics.
      These pathways impinge on several physiological processes, including development
      and maintenance of the nervous and immune systems, and epithelial morphogenesis.
      Elucidating how Abl-family kinases are regulated, and where and when they
      coordinate cytoskeletal changes, is essential for garnering a better
      understanding of these complex processes.

PMID- 19759286
TI  - DUOX2-derived reactive oxygen species are effectors of NOD2-mediated
      antibacterial responses.
AB  - Generation of microbicidal reactive oxygen species (ROS) is a pivotal protective
      component of the innate immune system in many eukaryotes. NOD (nucleotide
      oligomerisation domain containing protein)-like receptors (NLRs) have been
      implicated as phylogenetically ancient sensors of intracellular pathogens or
      endogenous danger signals. NOD2 recognizes the bacterial cell wall component
      muramyldipeptide leading to NFkappaB and MAPK activation via induced proximity
      signalling through the serine-threonine kinase RIP2. In addition to the
      subsequent induction of cytokines and antimicrobial peptides, NOD2 has been shown
      also to exert a direct antibacterial effect. Using a fluorescence-based ROS
      detection assay we demonstrate controlled ROS generation as an integral component
      of NOD2-induced signalling in epithelial cells. We demonstrate that the NAD(P)H
      oxidase family member DUOX2 is involved in NOD2-dependent ROS production.
      Coimmunoprecipitation and fluorescence microscopy were used to show that DUOX2
      interacts and colocalizes with NOD2 at the plasma membrane. Moreover,
      simultaneous overexpression of NOD2 and DUOX2 was found to result in cooperative
      protection against bacterial cytoinvasion using the Listeria monocytogenes
      infection model. RNAi-based studies revealed that DUOX2 is required for the
      direct bactericidal properties of NOD2. Our results demonstrate a new role of ROS
      as effector molecules of protective cellular signalling in response to a defined
      danger signal carried out by a mammalian intracellular NLR system.

PMID- 19759287
TI  - Kidins220/ARMS downregulation by excitotoxic activation of NMDARs reveals its
      involvement in neuronal survival and death pathways.
AB  - Functional and protein interactions between the N-methyl-D-aspartate type of
      glutamate receptor (NMDAR) and neurotrophin or ephrin receptors play essential
      roles in neuronal survival and differentiation. A shared downstream effector for
      neurotrophin- and ephrin-receptor signaling is kinase D-interacting substrate of
      220 kDa (Kidins220), also known as ankyrin repeat-rich membrane spanning (ARMS).
      Because this molecule is obligatory for neurotrophin-induced differentiation, we
      investigated whether Kidins220/ARMS and NMDAR functions were related. Here, we
      identify an association between these proteins and discover that excitotoxicity,
      a specific form of neuronal death induced by NMDAR overstimulation, dramatically
      decreases Kidins220/ARMS levels in cortical neurons and in a model of cerebral
      ischemia. Kidins220/ARMS downregulation is triggered by overactivation of NMDARs
      containing NR2B subunits and subsequent Ca(2+) influx, and involves a dual
      mechanism: rapid cleavage by the Ca(2+)-dependent protease calpain and calpain
      independent silencing of Kidins220/Arms gene transcription. Additionally,
      Kidins220/ARMS knockdown decreases ERK activation and basal neuronal viability,
      and enhances neuronal death under excitotoxic conditions. Our results demonstrate
      Kidins220/ARMS participation in neuronal life and death pathways, and constitute
      the first report of its regulation under pathological conditions.

PMID- 19759288
TI  - We must face the threats.

PMID- 19759289
TI  - Animal rights terrorists: what every neuroscientist should know.

PMID- 19759290
TI  - Novel hypotheses from a neuropsychological case study: is the visual ventral
      cortex critical for both category-generic and category-specific form perception?

PMID- 19759291
TI  - Medial prefrontal cortex, secondary hyperalgesia, and the default mode network.

PMID- 19759292
TI  - Stepwise maturation of apicobasal polarity of the neuroepithelium is essential
      for vertebrate neurulation.
AB  - During vertebrate neurulation, extensive cell movements transform the flat neural
      plate into the neural tube. This dynamic morphogenesis requires the tissue to
      bear a certain amount of plasticity to accommodate shape and position changes of
      individual cells as well as intercellular cohesiveness to maintain tissue
      integrity and architecture. For most of the neural plate-neural tube transition,
      cells are polarized along the apicobasal axis. The establishment and maintenance
      of this polarity requires many polarity proteins that mediate cell-cell adhesion
      either directly or indirectly. Intercellular adhesion reduces tissue plasticity
      and enhances tissue integrity. However, it remains unclear how apicobasal
      polarity is regulated to meet the opposing needs for tissue plasticity and tissue
      integrity during neurulation. Here, we show that N-Cad/ZO-1 complex-initiated
      apicobasal polarity is stabilized by the late-onsetting Lin7c/Nok complex after
      the extensive morphogenetic cell movements in neurulation. Loss of either N-Cad
      or Lin7c disrupts neural tube formation. Furthermore, precocious overexpression
      of Lin7c induces multiaxial mirror symmetry in zebrafish neurulation. Our data
      suggest that stepwise maturation of apicobasal polarity plays an essential role
      in vertebrate neurulation.

PMID- 19759293
TI  - Selective expression of ligand-gated ion channels in L5 pyramidal cell axons.
AB  - NMDA receptor (NMDAR)-dependent strengthening of neurotransmitter release has
      been widely observed, including in layer 5 (L5) pyramidal cells of the visual
      cortex, and is attributed to the axonal expression of NMDARs. However, we failed
      to detect NMDAR-mediated depolarizations or Ca(2+) entry in L5 pyramidal cell
      axons when focally stimulated with NMDAR agonists. This suggests that NMDARs are
      excluded from the axon. In contrast, local GABA(A) receptor activation alters
      axonal excitability, indicating that exclusion of ligand-gated ion channels from
      the axon is not absolute. Because NMDARs are restricted to the dendrite, NMDARs
      must signal to the axon by an indirect mechanism to alter release. Although
      subthreshold somatic depolarizations were found to spread electrotonically
      hundreds of micrometers through the axon, the resulting axonal potential was
      insufficient to open voltage-sensitive Ca(2+) channels. Therefore, if NMDAR
      mediated facilitation of release is cell autonomous, it may depend on voltage
      signaling but apparently is independent of changes in basal Ca(2+).
      Alternatively, this facilitation may be even less direct, requiring a cascade of
      events that are merely triggered by NMDAR activation.

PMID- 19759295
TI  - Reaching in depth: hand position dominates over binocular eye position in the
      rostral superior parietal lobule.
AB  - Neural activity was recorded in area PE (dorsorostral part of Brodmann's area 5)
      of the posterior parietal cortex while monkeys performed arm reaching toward
      memorized targets located at different distances from the body. For any given
      distance, arm movements were performed while the animal kept binocular eye
      fixation constant. Under these conditions, the activity of a large proportion
      (36%) of neurons was modulated by reach distance during the memory period. By
      varying binocular eye position (vergence angle) and initial hand position, we
      found that the reaching-related activity of most neurons (61%) was influenced by
      changing the starting position of the hand, whereas that of a smaller, although
      substantial, population (13%) was influenced by changes of binocular eye position
      (i.e., by the angle of vergence). Furthermore, the modulation of the neural
      activity was better explained expressing the reach movement end-point,
      corresponding to the memorized target location, in terms of distance from the
      initial hand position, rather than from the body. These results suggest that the
      activity of neurons in area PE combines information about eye and hand position
      to encode target distance for reaching in depth predominantly in hand
      coordinates. This encoding mechanism is consistent with the position of PE in the
      functional gradient that characterizes the parieto-frontal network underlying
      reaching.

PMID- 19759294
TI  - Antidepressant actions of histone deacetylase inhibitors.
AB  - Persistent symptoms of depression suggest the involvement of stable molecular
      adaptations in brain, which may be reflected at the level of chromatin
      remodeling. We find that chronic social defeat stress in mice causes a transient
      decrease, followed by a persistent increase, in levels of acetylated histone H3
      in the nucleus accumbens, an important limbic brain region. This persistent
      increase in H3 acetylation is associated with decreased levels of histone
      deacetylase 2 (HDAC2) in the nucleus accumbens. Similar effects were observed in
      the nucleus accumbens of depressed humans studied postmortem. These changes in H3
      acetylation and HDAC2 expression mediate long-lasting positive neuronal
      adaptations, since infusion of HDAC inhibitors into the nucleus accumbens, which
      increases histone acetylation, exerts robust antidepressant-like effects in the
      social defeat paradigm and other behavioral assays. HDAC inhibitor [N-(2
      aminophenyl)-4-[N-(pyridine-3-ylmethoxy-carbonyl)aminomethyl]benzamide (MS-275)]
      infusion also reverses the effects of chronic defeat stress on global patterns of
      gene expression in the nucleus accumbens, as determined by microarray analysis,
      with striking similarities to the effects of the standard antidepressant
      fluoxetine. Stress-regulated genes whose expression is normalized selectively by
      MS-275 may provide promising targets for the future development of novel
      antidepressant treatments. Together, these findings provide new insight into the
      underlying molecular mechanisms of depression and antidepressant action, and
      support the antidepressant potential of HDAC inhibitors and perhaps other agents
      that act at the level of chromatin structure.

PMID- 19759296
TI  - The convergence of information about rewarding and aversive stimuli in single
      neurons.
AB  - Neuroscientists, psychologists, clinicians, and economists have long been
      interested in how individuals weigh information about potential rewarding and
      aversive stimuli to make decisions and to regulate their emotions. However, we
      know relatively little about how appetitive and aversive systems interact in the
      brain, as most prior studies have investigated only one valence of reinforcement.
      Previous work has suggested that primate orbitofrontal cortex (OFC) represents
      information about the reward value of stimuli. We therefore investigated whether
      OFC also represents information about aversive stimuli, and, if so, whether
      individual neurons process information about both rewarding and aversive stimuli.
      Monkeys performed a trace conditioning task in which different novel abstract
      visual stimuli (conditioned stimuli, CSs) predicted the occurrence of one of
      three unconditioned stimuli (USs): a large liquid reward, a small liquid reward,
      or an aversive air-puff. Three lines of evidence suggest that information about
      rewarding and aversive stimuli converges in individual neurons in OFC. First, OFC
      neurons often responded to both rewarding and aversive USs, despite their
      different sensory features. Second, OFC neural responses to CSs often encoded
      information about both potential rewarding and aversive stimuli, even though
      these stimuli differed in both valence and sensory modality. Finally, OFC neural
      responses were correlated with monkeys' behavioral use of information about both
      rewarding and aversive CS-US associations. These data indicate that processing of
      appetitive and aversive stimuli converges at the single cell level in OFC,
      providing a possible substrate for executive and emotional processes that require
      using information from both appetitive and aversive systems.

PMID- 19759297
TI  - PP2A and GSK-3beta act antagonistically to regulate active zone development.
AB  - The synapse is composed of an active zone apposed to a postsynaptic cluster of
      neurotransmitter receptors. Each Drosophila neuromuscular junction comprises
      hundreds of such individual release sites apposed to clusters of glutamate
      receptors. Here, we show that protein phosphatase 2A (PP2A) is required for the
      development of structurally normal active zones opposite glutamate receptors.
      When PP2A is inhibited presynaptically, many glutamate receptor clusters are
      unapposed to Bruchpilot (Brp), an active zone protein required for normal
      transmitter release. These unapposed receptors are not due to presynaptic
      retraction of synaptic boutons, since other presynaptic components are still
      apposed to the entire postsynaptic specialization. Instead, these data suggest
      that Brp localization is regulated at the level of individual release sites. Live
      imaging of glutamate receptors demonstrates that this disruption to active zone
      development is accompanied by abnormal postsynaptic development, with decreased
      formation of glutamate receptor clusters. Remarkably, inhibition of the serine
      threonine kinase GSK-3beta completely suppresses the active zone defect, as well
      as other synaptic morphology phenotypes associated with inhibition of PP2A. These
      data suggest that PP2A and GSK-3beta function antagonistically to control active
      zone development, providing a potential mechanism for regulating synaptic
      efficacy at a single release site.

PMID- 19759298
TI  - Negative shift in the glycine reversal potential mediated by a Ca2+- and pH
      dependent mechanism in interneurons.
AB  - Cartwheel cells are glycinergic auditory interneurons which fire Na(+)- and
      Ca(2+)-dependent spike bursts, termed complex spikes, and which synapse on both
      principal cells and one another. The reversal potential for glycine (E(gly)) can
      be hyperpolarizing or depolarizing in cartwheel cells, and many cells are even
      excited by glycine. We explored the role of spike activity in determining E(gly)
      in mouse cartwheel cells using gramicidin perforated-patch recording. E(gly) was
      found to shift toward more negative potentials after a period of complex spiking
      or Ca(2+) spiking induced by depolarization, thus enhancing glycine's inhibitory
      effect for approximately 30 s following cessation of spiking. Combined perforated
      patch electrophysiology and imaging studies showed that the negative E(gly) shift
      was triggered by a Ca(2+)-dependent intracellular acidification. The effect on
      E(gly) was likely caused by bicarbonate-Cl(-) exchanger-mediated reduction in
      intracellular Cl(-), as H(2)DIDS and removal of HCO(3)(-)/CO(2) inhibited the
      negative E(gly) shift. The outward Cl(-) flux underlying the negative shift in
      E(gly) opposed a positive shift triggered by passive Cl(-) redistribution during
      the depolarization. Thus, a Ca(2+)-dependent mechanism serves to maintain or
      enhance the strength of inhibition in the face of increased excitatory activity.

PMID- 19759299
TI  - Reactive astrocytes form scar-like perivascular barriers to leukocytes during
      adaptive immune inflammation of the CNS.
AB  - Factors that regulate leukocyte entry and spread through CNS parenchyma during
      different types of CNS insults are incompletely understood. Reactive astrocytes
      have been implicated in restricting the spread of leukocytes from damaged into
      healthy parenchyma during the acute and local innate inflammatory events that
      follow CNS trauma, but the roles of reactive astrocytes during the chronic and
      widespread CNS inflammation associated with adaptive or acquired immune responses
      are uncertain. Here, we investigated the effects of transgenically targeted
      ablation of proliferating, scar-forming reactive astrocytes on the acquired
      immune inflammation associated with experimental autoimmune encephalitis (EAE).
      In wild-type mice with EAE, we found that reactive astrocytes densely surrounded
      perivascular clusters of leukocytes in a manner reminiscent of astrocyte scar
      formation after CNS trauma. Transgenically targeted ablation of proliferating
      astrocytes disrupted formation of these perivascular scars and was associated
      with a pronounced and significant increase in leukocyte entry into CNS
      parenchyma, including immunohistochemically identified macrophages, T lymphocytes
      and neutrophils. This exacerbated inflammation was associated with a
      substantially more severe and rapidly fulminant clinical course. These findings
      provide experimental evidence that reactive astrocytes form scar-like
      perivascular barriers that restrict the influx of leukocytes into CNS parenchyma
      and protect CNS function during peripherally initiated, acquired immune
      inflammatory responses in the CNS. The findings suggest that loss or disruption
      of astrocyte functions may underlie or exacerbate the inflammation and
      pathologies associated with autoimmune diseases of the CNS, including multiple
      sclerosis.

PMID- 19759300
TI  - The representation of tool use in humans and monkeys: common and uniquely human
      features.
AB  - Though other species of primates also use tools, humans appear unique in their
      capacity to understand the causal relationship between tools and the result of
      their use. In a comparative fMRI study, we scanned a large cohort of human
      volunteers and untrained monkeys, as well as two monkeys trained to use tools,
      while they observed hand actions and actions performed using simple tools. In
      both species, the observation of an action, regardless of how performed,
      activated occipitotemporal, intraparietal, and ventral premotor cortex,
      bilaterally. In humans, the observation of actions done with simple tools yielded
      an additional, specific activation of a rostral sector of the left inferior
      parietal lobule (IPL). This latter site was considered human-specific, as it was
      not observed in monkey IPL for any of the tool videos presented, even after
      monkeys had become proficient in using a rake or pliers through extensive
      training. In conclusion, while the observation of a grasping hand activated
      similar regions in humans and monkeys, an additional specific sector of IPL
      devoted to tool use has evolved in Homo sapiens, although tool-specific neurons
      might reside in the monkey grasping regions. These results shed new light on the
      changes of the hominid brain during evolution.

PMID- 19759301
TI  - Spatial spread of the local field potential and its laminar variation in visual
      cortex.
AB  - We developed a new method to estimate the spatial extent of summation, the
      cortical spread, of the local field potential (LFP) throughout all layers of
      macaque primary visual cortex V1 by taking advantage of the V1 retinotopic map.
      We mapped multi-unit activity and LFP visual responses with sparse-noise at
      several cortical sites simultaneously. The cortical magnification factor near the
      recording sites was precisely estimated by track reconstruction. The new method
      combined experimental measurements together with a model of signal summation to
      obtain the cortical spread of the LFP. This new method could be extended to
      cortical areas that have topographic maps such as S1 or A1, and to cortical areas
      without functional columnar maps, such as rodent visual cortex. In macaque V1,
      the LFP was the sum of signals from a very local region, the radius of which was
      on average 250 microm. The LFP's cortical spread varied across cortical layers,
      reaching a minimum value of 120 microm in layer 4B. An important functional
      consequence of the small cortical spread of the LFP is that the visual field maps
      of LFP and MUA recorded at a single electrode site were very similar. The similar
      spatial scale of the visual responses, the restricted cortical spread, and their
      laminar variation led to new insights about the sources and possible applications
      of the LFP.

PMID- 19759302
TI  - Striatal expression of a calmodulin fragment improved motor function, weight
      loss, and neuropathology in the R6/2 mouse model of Huntington's disease.
AB  - Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder,
      caused by a polyglutamine expansion in the huntingtin protein (htt). Increasing
      evidence suggests that transglutaminase (TGase) plays a critical role in the
      pathophysiology of HD possibly by stabilizing monomeric, polymeric and aggregated
      htt. We previously reported that in HEK293 and SH-SY5Y cells expression of a
      calmodulin (CaM)-fragment, consisting of amino acids 76-121 of CaM, decreased
      binding of CaM to mutant htt, TGase-modified htt and cytotoxicity associated with
      mutant htt and normalized intracellular calcium release. In this study, an adeno
      associated virus (AAV) that expresses the CaM-fragment was injected into the
      striatum of HD transgenic R6/2 mice. The CaM-fragment significantly reduced body
      weight loss and improved motor function as indicated by improved rotarod
      performance, longer stride length, lower stride frequency, fewer low mobility
      bouts and longer travel distance than HD controls. A small but insignificant
      increase in survival was observed in R6/2 mice with CaM-fragment expression.
      Immunoprecipitation studies show that expression of the CaM-fragment reduced
      TGase-modified htt in the striatum of R6/2 mice. The percentage of htt-positive
      nuclei and the size of intranuclear htt aggregates were reduced by the CaM
      fragment without striatal volume changes. The effects of CaM-fragment appear to
      be selective, as activity of another CaM-dependent enzyme, CaM-dependent kinase
      II, was not altered. Moreover, inhibition of TGase-modified htt was substrate
      specific since overall TGase activity in the striatum was not altered by
      treatment with the CaM-fragment. Together, these results suggest that disrupting
      CaM-htt interaction may provide a new therapeutic strategy for HD.

PMID- 19759303
TI  - Decisions in changing conditions: the urgency-gating model.
AB  - Several widely accepted models of decision making suggest that, during simple
      decision tasks, neural activity builds up until a threshold is reached and a
      decision is made. These models explain error rates and reaction time
      distributions in a variety of tasks and are supported by neurophysiological
      studies showing that neural activity in several cortical and subcortical regions
      gradually builds up at a rate related to task difficulty and reaches a relatively
      constant level of discharge at a time that predicts movement initiation. The
      mechanism responsible for this buildup is believed to be related to the temporal
      integration of sequential samples of sensory information. However, an alternative
      mechanism that may explain the neural and behavioral data is one in which the
      buildup of activity is instead attributable to a growing signal related to the
      urgency to respond, which multiplicatively modulates updated estimates of sensory
      evidence. These models are difficult to distinguish when, as in previous studies,
      subjects are presented with constant sensory evidence throughout each trial. To
      distinguish the models, we presented human subjects with a task in which evidence
      changed over the course of each trial. Our results are more consistent with
      "urgency gating" than with temporal integration of sensory samples and suggest a
      simple mechanism for implementing trade-offs between the speed and accuracy of
      decisions.

PMID- 19759304
TI  - The role of granulocyte-colony stimulating factor (G-CSF) in the healthy brain: a
      characterization of G-CSF-deficient mice.
AB  - Granulocyte-colony stimulating factor (G-CSF) is a hematopoietic growth factor
      that controls proliferation and differentiation of neural stem cells. Although
      recent studies have begun to explore G-CSF-related mechanisms of action in
      various disease models, little is known about its function in the healthy brain.
      In the present study, the effect of G-CSF deficiency on memory formation and
      motor skills was investigated. The impact of G-CSF deficiency on the structural
      integrity of the hippocampus was evaluated by analyzing the generation of
      doublecortin-expressing cells, the amount of bromodeoxyurine-labeled cells, the
      dendritic complexity in hippocampal neurons, the binding densities of NMDA and
      GABA(A) receptors and the induction of long-term potentiation (LTP). G-CSF
      deficiency caused a disruption in memory formation and in the development of
      motor skills. These impairments were associated with reduced ligand binding
      densities of NMDA receptors in hippocampal subfields CA3 and the dentate gyrus.
      The reduced excitation was potentiated by increased ligand binding densities of
      GABA(A) receptors resulting in a relative shift in favor of inhibition and
      impaired behavioral performance. These alterations were accompanied by impaired
      induction of LTP in the CA1 region. Moreover, G-CSF deficiency led to decreased
      dendritic complexity in hippocampal neurons in the dentate gyrus and the CA1
      region. G-CSF deficiency also caused a reduction of neuronal precursor cells in
      the dentate gyrus. These findings confirm G-CSF as an essential neurotrophic
      factor, and point to a role in the proliferation, differentiation and functional
      integration of neural cells necessary for the structural and functional integrity
      of the hippocampal formation.

PMID- 19759305
TI  - Enhanced Stat3 activation in POMC neurons provokes negative feedback inhibition
      of leptin and insulin signaling in obesity.
AB  - Leptin-stimulated Stat3 activation in proopiomelanocortin (POMC)-expressing
      neurons of the hypothalamus plays an important role in maintenance of energy
      homeostasis. While Stat3 activation in POMC neurons is required for POMC
      expression, the role of elevated basal Stat3 activation as present in the
      development of obesity has not been directly addressed. Here, we have generated
      and characterized mice expressing a constitutively active version of Stat3 (Stat3
      C) in POMC neurons (Stat3-C(POMC) mice). On normal chow diet, these animals
      develop obesity as a result of hyperphagia and decreased POMC expression
      accompanied by central leptin and insulin resistance. This unexpected finding
      coincides with POMC-cell-specific, Stat3-mediated upregulation of SOCS3
      expression inhibiting both leptin and insulin signaling as insulin-stimulated
      PIP(3) (phosphatidylinositol-3,4,5 triphosphate) formation and protein kinase B
      (AKT) activation in POMC neurons as well as with the fact that insulin's ability
      to hyperpolarize POMC neurons is largely reduced in POMC cells of Stat3-C(POMC)
      mice. These data indicate that constitutive Stat3 activation is not sufficient to
      promote POMC expression but requires simultaneous PI3K (phosphoinositide 3
      kinase)-dependent release of FOXO1 repression. In contrast, upon exposure to a
      high-fat diet, food intake and body weight were unaltered in Stat3-C(POMC) mice
      compared with control mice. Taken together, these experiments directly
      demonstrate that enhanced basal Stat3 activation in POMC neurons as present in
      control mice upon high-fat feeding contributes to the development of hypothalamic
      leptin and insulin resistance.

PMID- 19759306
TI  - Neuropathy target esterase is required for adult vertebrate axon maintenance.
AB  - The enzyme neuropathy target esterase (NTE) is present in neurons and deacylates
      the major membrane phospholipid, phosphatidylcholine (PtdCho). Mutation of the
      NTE gene or poisoning by neuropathic organophosphates--chemical inhibitors of NTE
      -causes distal degeneration of long spinal axons in humans. However, analogous
      neuropathological changes have not been reported in nestin-cre:NTEfl/fl mice with
      NTE-deficient neural tissue. Furthermore, altered PtdCho homeostasis has not been
      detected in NTE-deficient vertebrates. Here, we describe distal degeneration of
      the longest spinal axons in approximately 3-week-old nestin-cre:NTEfl/fl mice and
      in adult C57BL/6J mice after acute dosing with a neuropathic organophosphate: in
      both groups early degenerative lesions were followed by swellings comprising
      accumulated axoplasmic material. In mice dosed acutely with organophosphate,
      maximal numbers of lesions, in the longest spinal sensory axon tract, were
      attained within days and were preceded by a transient rise in neural PtdCho. In
      nestin-cre:NTEfl/fl mice, sustained elevation of PtdCho over many months was
      accompanied by progressive degeneration and massive swelling of axons in sensory
      and motor spinal tracts and by increasing hindlimb dysfunction. Axonal lesion
      distribution closely resembled that in hereditary spastic paraplegia (HSP). The
      importance of defective membrane trafficking in HSP and the association of NTE
      with the endoplasmic reticulum--the starting point for the constitutive secretory
      pathway and transport of neuronal materials into axons--prompted investigation
      for a role of NTE in secretion. Cultured NTE-deficient neurons displayed modestly
      impaired secretion, consistent with neuronal viability and damage in vivo
      initially restricted to distal parts of the longest axons.

PMID- 19759307
TI  - Activity of Hb9 interneurons during fictive locomotion in mouse spinal cord.
AB  - Hb9 interneurons (Hb9 INs) are putative components of the mouse spinal locomotor
      central pattern generator (CPG) and candidates for the rhythm-generating kernel.
      Studies in slices and hemisected spinal cords showed that Hb9 INs display TTX
      resistant membrane potential oscillations, suggesting a role in rhythm
      generation. To further investigate the roles of Hb9 INs in the locomotor CPG, we
      used two-photon calcium imaging in the in vitro isolated whole neonatal mouse
      spinal cord preparation to record the activity of Hb9 INs, which were
      subsequently stained for unambiguous genetic identification. We elicited fictive
      locomotion by transmitter application or by electrically stimulating the caudal
      tip of the spinal cord. Although most Hb9 INs were rhythmically active during
      fictive locomotion, their activity was sparse and they failed to fire with each
      cycle of the episode. If Hb9 INs are the principal pacemakers of the CPG in the
      hemisegment in which they are located, they should direct the firing of motor
      neurons, with their activity preceding that of their ipsilateral segmental
      ventral roots. Instead, during each locomotor cycle, onset of Hb9 IN activity
      lagged behind the onset of the ipsilateral ventral root burst by a mean phase of
      0.21 during electrical stimulation and 0.28 during transmitter application. Whole
      cell recordings in intact and hemisected spinal cords confirmed the imaging
      results. Our data suggest that Hb9 INs participate in fictive locomotion, but the
      delayed onset of activity relative to ipsilateral motoneurons suggests that Hb9
      INs are unlikely to be the sole intrasegmental rhythm-generating kernel of the
      CPG.

PMID- 19759308
TI  - The structural integrity of an amygdala-prefrontal pathway predicts trait
      anxiety.
AB  - Here, we used diffusion tensor imaging (DTI) and showed that the strength of an
      axonal pathway identified between the amygdala and prefrontal cortex predicted
      individual differences in trait anxiety. A functional magnetic resonance imaging
      (fMRI) functional localizer that has been shown to produce reliable amygdala
      activation was collected in 20 psychiatrically healthy subjects. Voxelwise
      regression analyses using this fMRI amygdala reactivity as a regressor were
      performed on fractional anisotropy images derived from DTI. This analysis
      identified a white matter pathway between the amygdala and ventromedial
      prefrontal cortex. Individual differences in the structural integrity of this
      putative amygdala-prefrontal pathway were inversely correlated with trait anxiety
      levels (i.e., higher pathway strength predicted lower anxiety). More generally,
      this study illustrates a strategy for combining fMRI and DTI to identify
      individual differences in structural pathways that predict behavioral outcomes.

PMID- 19759309
TI  - Orbitofrontal and anterior cingulate cortex neurons selectively process cocaine
      associated environmental cues in the rhesus monkey.
AB  - Encounters with stimuli associated with drug use are believed to contribute to
      relapse. To probe the neurobiology of environmentally triggered drug use, we have
      conducted single-unit recordings in rhesus monkeys during presentation of two
      distinct types of drug paired cues that differentially support drug-seeking. The
      animals were highly conditioned to these cues via exposure during self
      administration procedures conducted over a 4 year period. The cues studied were a
      discriminative cue that signaled response-contingent availability of cocaine, and
      a discrete cue that was temporally paired with the cocaine infusion (0.1 or 0.5
      mg/kg). Two cortical regions consistently activated by cocaine-associated cues in
      human imaging studies are the orbitofrontal (OFC) and anterior cingulate cortex
      (ACC), though little is known about cortical neuronal activity responses to drug
      cues. We simultaneously recorded single-unit activity in OFC and ACC as well as
      in dorsal striatum in rhesus monkeys during cocaine self-administration. Dorsal
      striatal neurons were less engaged by drug cues than cortical regions. Between
      OFC and ACC, distinct functionality was apparent in neuronal responses. OFC
      neurons preferentially responded to the discriminative cue, consistent with a
      role in cue-induced drug-seeking. In contrast, the ACC did not respond more to
      the discriminative cue than to the discrete cue. Also distinct from the OFC, ACC
      showed sustained firing throughout the 18 s duration of the discrete cue. This
      pattern of sustained activation in ACC is consistent with a role in reward
      expectation and/or in mediating behavioral effects of discrete cues paired with
      drug infusions.

PMID- 19759310
TI  - APC2 plays an essential role in axonal projections through the regulation of
      microtubule stability.
AB  - Growth cones at the tip of growing axons are key cellular structures that detect
      guidance cues and mediate axonal growth. An increasing number of studies have
      suggested that the dynamic regulation of microtubules in the growth cone plays an
      essential role in growth cone steering. The dynamic properties of microtubules
      are considered to be regulated by variegated cellular factors but, in particular,
      through microtubule-interacting proteins. Here, we examined the functional role
      of adenomatous polyposis coli-like molecule 2 (APC2) in the development of axonal
      projections by using the chick retinotectal topographic projection system. APC2
      is preferentially expressed in the nervous system from early developmental stages
      through to adulthood. Immunohistochemical analysis revealed that APC2 is
      distributed along microtubules in growth cones as well as axon shafts of retinal
      axons. Overexpression of APC2 in cultured cells induced the stabilization of
      microtubules, whereas the knockdown of APC2 in chick retinas with specific short
      hairpin RNA reduced the stability of microtubules in retinal axons. APC2
      knockdown retinal axons showed abnormal growth attributable to a reduced response
      to ephrin-A2 in vitro. Furthermore, they showed drastic alterations in
      retinotectal projections without making clear target zones in the tectum in vivo.
      These results suggest that APC2 plays a critical role in the development of the
      nervous system through the regulation of microtubule stability.

PMID- 19759311
TI  - Multisensory congruency as a mechanism for attentional control over perceptual
      selection.
AB  - The neural mechanisms underlying attentional selection of competing neural
      signals for awareness remains an unresolved issue. We studied attentional
      selection, using perceptually ambiguous stimuli in a novel multisensory paradigm
      that combined competing auditory and competing visual stimuli. We demonstrate
      that the ability to select, and attentively hold, one of the competing
      alternatives in either sensory modality is greatly enhanced when there is a
      matching cross-modal stimulus. Intriguingly, this multimodal enhancement of
      attentional selection seems to require a conscious act of attention, as passively
      experiencing the multisensory stimuli did not enhance control over the stimulus.
      We also demonstrate that congruent auditory or tactile information, and combined
      auditory-tactile information, aids attentional control over competing visual
      stimuli and visa versa. Our data suggest a functional role for recently found
      neurons that combine voluntarily initiated attentional functions across sensory
      modalities. We argue that these units provide a mechanism for structuring
      multisensory inputs that are then used to selectively modulate early (unimodal)
      cortical processing, boosting the gain of task-relevant features for willful
      control over perceptual awareness.

PMID- 19759312
TI  - GABA(B) receptor activation triggers BDNF release and promotes the maturation of
      GABAergic synapses.
AB  - GABA, the main inhibitory neurotransmitter in the adult brain, has recently
      emerged as an important signal in network development. Most of the trophic
      functions of GABA have been attributed to depolarization of the embryonic and
      neonatal neurons via the activation of ionotropic GABA(A) receptors. Here we
      demonstrate a novel mechanism by which endogenous GABA selectively regulates the
      development of GABAergic synapses in the developing brain. Using whole-cell patch
      clamp recordings on newborn mouse hippocampi lacking functional GABA(B) receptors
      (GABA(B)-Rs) and time-lapse fluorescence imaging on cultured hippocampal neurons
      expressing GFP-tagged brain-derived neurotrophic factor (BDNF), we found that
      activation of metabotropic GABA(B) receptors (GABA(B)-Rs) triggers secretion of
      BDNF and promotes the development of perisomatic GABAergic synapses in the
      newborn mouse hippocampus. Because activation of GABA(B)-Rs occurs during the
      characteristic ongoing physiological network-driven synaptic activity present in
      the developing hippocampus, our results reveal a new mechanism by which synaptic
      activity can modulate the development of local GABAergic synaptic connections in
      the developing brain.

PMID- 19759313
TI  - Mapping a barbiturate withdrawal locus to a 0.44 Mb interval and analysis of a
      novel null mutant identify a role for Kcnj9 (GIRK3) in withdrawal from
      pentobarbital, zolpidem, and ethanol.
AB  - Here, we map a quantitative trait locus (QTL) with a large effect on
      predisposition to barbiturate (pentobarbital) withdrawal to a 0.44 Mb interval of
      mouse chromosome 1 syntenic with human 1q23.2. We report a detailed analysis of
      the genes within this interval and show that it contains 15 known and predicted
      genes, 12 of which demonstrate validated genotype-dependent transcript expression
      and/or nonsynonymous coding sequence variation that may underlie the influence of
      the QTL on withdrawal. These candidates are involved in diverse cellular
      functions including intracellular trafficking, potassium conductance and spatial
      buffering, and multimolecular complex dynamics, and indicate both established and
      novel aspects of neurobiological response to sedative-hypnotics. This work
      represents a substantial advancement toward identification of the gene(s) that
      underlie the phenotypic effects of the QTL. We identify Kcnj9 as a particularly
      promising candidate and report the development of a Kcnj9-null mutant model that
      exhibits significantly less severe withdrawal from pentobarbital as well as other
      sedative-hypnotics (zolpidem and ethanol) versus wild-type littermates. Reduced
      expression of Kcnj9, which encodes GIRK3 (Kir3.3), is associated with less severe
      sedative-hypnotic withdrawal. A multitude of QTLs for a variety of complex
      traits, including diverse responses to sedative-hypnotics, have been detected on
      distal chromosome 1 in mice, and as many as four QTLs on human chromosome 1q have
      been implicated in human studies of alcohol dependence. Thus, our results will be
      primary to additional efforts to identify genes involved in a wide variety of
      behavioral responses to sedative-hypnotics and may directly facilitate progress
      in human genetics.

PMID- 19759314
TI  - Axonal targeting of Trk receptors via transcytosis regulates sensitivity to
      neurotrophin responses.
AB  - Axonal targeting of trophic receptors is critical for neuronal responses to
      extracellular developmental cues, yet the underlying trafficking mechanisms
      remain unclear. Here, we report that tropomyosin-related kinase (Trk) receptors
      for target-derived neurotrophins are anterogradely trafficked to axons via
      transcytosis in sympathetic neurons. Using compartmentalized cultures, we show
      that mature receptors on neuronal soma surfaces are endocytosed and remobilized
      via Rab11-positive recycling endosomes into axons. Inhibition of dynamin
      dependent endocytosis disrupted anterograde transport and localization of TrkA
      receptors in axons. Anterograde TrkA delivery and exocytosis into axon growth
      cones is enhanced by nerve growth factor (NGF), acting locally on distal axons.
      Perturbing endocytic recycling attenuated NGF-dependent signaling and axon growth
      while enhancing recycling conferred increased neuronal sensitivity to NGF. Our
      results reveal regulated transcytosis as an unexpected mode of Trk trafficking
      that serves to rapidly mobilize ready-synthesized receptors to growth cones, thus
      providing a positive feedback mechanism by which limiting concentrations of
      target-derived neurotrophins enhance neuronal sensitivity.

PMID- 19759315
TI  - Mechanisms of tactile information transmission through whisker vibrations.
AB  - In their natural environment, rodents use their whiskers to locate and
      distinguish between objects of different textures and shapes. They do so by
      moving their whiskers actively as well as passively, through body and head
      movements. To determine the mechanisms by which surface coarseness is translated
      into neuronal discharges through passive whisker movements, we monitored head
      movements of awake behaving rats while approaching objects. We then replayed
      these movements in anesthetized rats, monitored the whiskers' movements across
      various surfaces, and concurrently recorded the activity of first-order sensory
      neurons. We found that whiskers, being the first stage of sensory information
      translation, shape transduction by amplifying small-amplitude high-frequency
      signals. Thus, surface coarseness is transmitted through high-velocity
      micromotions. Consistent with this, we find that during surface contact, discrete
      high-velocity movements, or stick-slip events, evoke first-order neuronal
      discharge. Transient ringing in whiskers, which primarily represents resonance
      vibrations, follows these events, but seldom causes neurons to discharge. These
      sensory transformations are influenced by the whiskers' biomechanical properties.
      To determine the resemblance of these tactile transformations during passive
      whisker movements and active whisking, we induced artificial whisking across
      various surface textures. We found that the processes by which tactile
      information becomes available to the animal are similar for these different modes
      of behavior. Together, these findings indicate that the temporal bandpass
      properties for spike generation in first-order neurons are matched by the
      biomechanical characteristics of whiskers, which translate surface coarseness
      into high-frequency whisker micromotions. These properties enable rodents to
      acquire tactile information through passive and active movements of their
      whiskers.

PMID- 19759316
TI  - Basal forebrain lactate release and promotion of cortical arousal during
      prolonged waking is attenuated in aging.
AB  - The wake-promoting basal forebrain (BF) is critically involved in sustaining
      cortical arousal. In the present study, we investigated how aging affects the
      capacity of the BF to cope with continuous activation during prolonged waking.
      Increased neuronal activity induces lactate release in the activated brain area,
      and BF stimulation increases cortical arousal. We used in vivo microdialysis to
      measure lactate levels in the BF, and electroencephalography (EEG) to measure
      cortical arousal, during 3 h sleep deprivation (SD) in three age groups of rats.
      Lactate increased during SD in young but not in aged (middle-aged and old) rats.
      The increase in high-frequency (HF) EEG theta power (7-9 Hz), a marker of
      cortical arousal and active waking, was attenuated in the aged. Furthermore, a
      positive correlation between BF lactate release and HF EEG theta increase was
      found in young but not in aged rats. We hypothesized that these age-related
      attenuations result from reduced capacity of the BF to respond to increased
      neuronal activation. This was tested by stimulating the BF with glutamate
      receptor agonist NMDA. Whereas BF stimulation increased waking in young and old
      rats, lactate increase and the HF EEG theta increase were attenuated in the old.
      Also, the homeostatic increase in sleep intensity after SD was attenuated in aged
      rats. Our results suggest that an age-related attenuation in BF function reduces
      cortical arousal during prolonged waking. As the quality of waking is important
      in regulating the subsequent sleep, reduced cortical arousal during SD may
      contribute to the age-related reduction in sleep intensity.

PMID- 19759317
TI  - Voluntary motor output is altered by spike-timing-dependent changes in the human
      corticospinal pathway.
AB  - Repeated pairs of timed presynaptic and postsynaptic potentials cause lasting
      changes in efficacy of transmission at many synapses. The corticospinal tract is
      the major pathway controlling voluntary movement in humans, and corticospinal
      neurons have monosynaptic connections to motoneurons of many muscles. We
      hypothesized that corticospinal transmission in humans could be altered by
      delivering, to the corticospinal-motoneuronal synapses, timed pairs of
      presynaptic volleys (produced by cortical stimulation) and antidromic
      postsynaptic volleys (by peripheral nerve stimulation). To test corticospinal
      transmission, electrical cervicomedullary stimuli evoked motor responses
      [cervicomedullary motor-evoked potentials (CMEPs)] in biceps brachii before and
      for 1 h after conditioning with 50 paired cortical and peripheral nerve stimuli.
      Seven interstimulus intervals (ISIs) of conditioning stimulus pairs were tested
      on different days. With one ISI (+3 ms; cortical before peripheral nerve
      stimulation), CMEPs were significantly increased in size by 33 +/- 30% (mean +/-
      SD; n = 7) from 4 until 32 min after conditioning. With two other ISIs (-13 ms,
      +22 ms), CMEPs were decreased from approximately 30 until 60 min after
      conditioning (by 25 +/- 23% and 27 +/- 32%; n = 8). The remaining ISIs produced
      no changes. In a second study, subjects performed weak bilateral voluntary elbow
      flexion contractions before and after conditioning of the right elbow flexors.
      Conditioning ISIs that increased or decreased CMEPs similarly increased or
      decreased voluntary force and EMG on the right. Thus, depending on their timing,
      repeated paired stimuli can potentiate or depress corticospinal transmission, and
      these changes are functionally relevant. We suggest that bidirectional spike
      timing-dependent plasticity can be induced at corticospinal-motoneuronal synapses
      and can influence voluntary motor output.

PMID- 19759318
TI  - Effect of the calcimimetic R-568 [3-(2-chlorophenyl)-N-((1R)-1-(3
      methoxyphenyl)ethyl)-1-propanamine] on correcting inactivating mutations in the
      human calcium-sensing receptor.
AB  - Over 257 mutations in the human calcium-sensing receptor (hCaSR) gene have been
      reported. Heterozygous inactivating mutations can result in familial
      hypocalciuric hypercalcemia (FHH), whereas homozygous inactivating mutations can
      cause life-threatening neonatal severe hyperparathyroidism (NSHPT). Activating
      mutations in the hCaSR can result in hypercalciuria and hypocalcemia. A recent
      publication on the successful treatment of a patient suffering from FHH with the
      hCaSR positive allosteric modulator cinacalcet prompted our interest in exploring
      the molecular pharmacology of calcimimetics to correct signaling defects
      associated with inactivating hCaSR mutations. We prepared 11 mutant hCaSRs,
      previously identified in patients suffering from NSHPT or FHH, and tested their
      ability to couple to inositol phosphate accumulation and intracellular calcium
      mobilization in transiently transfected human embryonic kidney 293 and Chines
      hamster ovary cells using the calcimimetic R-568 [3-(2-chlorophenyl)-N-((1R)-1-(3
      methoxyphenyl)ethyl)-1-propanamine]. We found that extracellular Ca(2+) was
      significantly less potent on the mutated receptors compared with wild-type hCaSR.
      However, R-568 was able to enhance the potency of extracellular Ca(2+) toward the
      mutant hCaSRs. Furthermore, R-568 increased the maximal agonist response on
      several of the mutant CaSRs. We applied a novel operational model of allosteric
      modulation/agonism that provided a common mechanism to account for the behavior
      of the wild-type and mutant hCaSRs. The data provide evidence for the potential
      use of calcimimetics to treat diseases such as FHH and NSHPT where severe
      hypercalcemia can be life-threatening.

PMID- 19759319
TI  - Omigapil ameliorates the pathology of muscle dystrophy caused by laminin-alpha2
      deficiency.
AB  - Laminin alpha2-deficient congenital muscular dystrophy, called MDC1A, is a rare,
      devastating genetic disease characterized by severe neonatal hypotonia ("floppy
      infant syndrome"), peripheral neuropathy, inability to stand or walk, respiratory
      distress, and premature death in early life. Transgenic overexpression of the
      apoptosis inhibitor protein BCL-2, or deletion of the proapoptotic Bax gene in a
      mouse model for MDC1A prolongs survival and mitigates pathology, indicating that
      apoptotic events are involved in the pathology. Here we demonstrate that the
      proapoptotic glyceraldehyde-3-phosphate dehydrogenase (GAPDH)-Siah1-CBP/p300-p53
      pathway is activated in a mouse model for MDC1A. Moreover, we show that omigapil,
      which inhibits GAPDH-Siah1-mediated apoptosis, ameliorates several pathological
      hallmarks in the MDC1A mouse model. Specifically, we demonstrate that treatment
      with omigapil inhibits apoptosis in muscle, reduces body weight loss and skeletal
      deformation, increases locomotive activity, and protects from early mortality.
      These data qualify omigapil, which is in late phase of clinical development for
      human use, as a drug candidate for the treatment of MDC1A.

PMID- 19759320
TI  - Filling-in, spatial summation, and radiation of pain: evidence for a neural
      population code in the nociceptive system.
AB  - The receptive field organization of nociceptive neurons suggests that noxious
      information may be encoded by population-based mechanisms. Electrophysiological
      evidence of population coding mechanisms has remained limited. However,
      psychophysical studies examining interactions between multiple noxious stimuli
      can provide indirect evidence that neuron population recruitment can contribute
      to both spatial and intensity-related percepts of pain. In the present study,
      pairs of thermal stimuli (35 degrees C/49 degrees C or 49 degrees C/49 degrees C)
      were delivered at different distances on the leg (0, 5, 10, 20, 40 cm) and
      abdomen (within and across dermatomes) and subjects evaluated pain intensity and
      perceived spatial attributes of stimuli. Reports of perceived pain spreading to
      involve areas that were not stimulated (radiation of pain) were most frequent at
      5- and 10-cm distances (chi(2) = 34.107, P < 0.0001). Perceived connectivity
      between two noxious stimuli (filling-in) was influenced by the distance between
      stimuli (chi(2) = 16.756, P < 0.01), with the greatest connectivity reported at 5
      and 10-cm separation distances. Spatial summation of pain occurred over probe
      separation distances as large as 40 cm and six dermatomes (P < 0.05), but was
      maximal at 5- and 10-cm separation distances. Taken together, all three of these
      phenomena suggest that interactions between recruited populations of neurons may
      support both spatial and intensity-related dimensions of the pain experience.

PMID- 19759321
TI  - Influence of context and behavior on stimulus reconstruction from neural activity
      in primary auditory cortex.
AB  - Population responses of cortical neurons encode considerable details about
      sensory stimuli, and the encoded information is likely to change with stimulus
      context and behavioral conditions. The details of encoding are difficult to
      discern across large sets of single neuron data because of the complexity of
      naturally occurring stimulus features and cortical receptive fields. To overcome
      this problem, we used the method of stimulus reconstruction to study how complex
      sounds are encoded in primary auditory cortex (AI). This method uses a linear
      spectro-temporal model to map neural population responses to an estimate of the
      stimulus spectrogram, thereby enabling a direct comparison between the original
      stimulus and its reconstruction. By assessing the fidelity of such
      reconstructions from responses to modulated noise stimuli, we estimated the range
      over which AI neurons can faithfully encode spectro-temporal features. For
      stimuli containing statistical regularities (typical of those found in complex
      natural sounds), we found that knowledge of these regularities substantially
      improves reconstruction accuracy over reconstructions that do not take advantage
      of this prior knowledge. Finally, contrasting stimulus reconstructions under
      different behavioral states showed a novel view of the rapid changes in spectro
      temporal response properties induced by attentional and motivational state.

PMID- 19759322
TI  - Normal spatial attention but impaired saccades and visual motion perception after
      lesions of the monkey cerebellum.
AB  - Lesions of the cerebellum produce deficits in movement and motor learning.
      Saccadic dysmetria, for example, is caused by lesions of the posterior cerebellar
      vermis. Monkeys and patients with such lesions are unable to modify the amplitude
      of saccades. Some have suggested that the effects on eye movements might reflect
      a more global cognitive deficit caused by the cerebellar lesion. We tested that
      idea by studying the effects of vermis lesions on attention as well as saccadic
      eye movements, visual motion perception, and luminance change detection. Lesions
      in posterior vermis of four monkeys caused the known deficits in saccadic
      control. Attention tested by examination of acuity threshold changes induced by
      prior cueing of the location of the targets remained normal after vermis lesions.
      Luminance change detection was also unaffected by the lesions. In one case, after
      a lesion restricted to lobulus VIII, the animal had impaired visual motion
      perception.

PMID- 19759323
TI  - Distinct electrophysiological properties in subtypes of nonspiking olfactory
      local interneurons correlate with their cell type-specific Ca2+ current profiles.
AB  - A diverse population of local interneurons (LNs) helps to process, structure, and
      spatially represent olfactory information in the insect antennal lobe. In
      Periplaneta americana, we identified two subtypes of nonspiking local
      interneurons (type II LNs) by their distinct morphological and intrinsic
      electrophysiological properties. As an important step toward a better
      understanding of the cellular mechanisms that mediate odor information
      processing, we present a detailed analysis of their distinct voltage-activated
      Ca(2+) currents, which clearly correlated with their distinct intrinsic
      electrophysiological properties. Both type II LNs did not posses voltage
      activated Na(+) currents and apparently innervated all glomeruli including the
      macroglomerulus. Type IIa LNs had significant longer and thicker low-order
      neurites and innervated each glomerulus entirely and homogeneously, whereas type
      IIb LNs innervated only parts of each glomerulus. All type II LNs were broadly
      tuned and responded to odorants of many chemical classes with graded changes in
      the membrane potential. Type IIa LNs responded with odor-specific elaborate
      patterns of excitation that could also include "spikelets" riding on the
      depolarizations and periods of inhibition. In contrast, type IIb LNs responded
      mostly with sustained, relatively smooth depolarizations. Consistent with the
      strong active membrane properties of type IIa LNs versus type IIb LNs, the
      voltage-activated Ca(2+) current of type IIa LNs activated at more hyperpolarized
      membrane potentials and had a larger transient component.

PMID- 19759324
TI  - Multicomponent control strategy underlying production of maximal hand velocity
      during horizontal arm swing.
AB  - Movement control responsible for generation of maximal hand velocity was studied
      on the example of horizontal arm swing that is a component of various sports
      activities. The movement was performed with the nondominant arm in similarity
      with the baseball bat swing. The task was to generate maximum hand velocity at a
      target. The movement included trunk long-axis rotation and horizontal shoulder
      and elbow extension. Kinematics and torque analyses were performed to study the
      organization of fastest movements and to compare trials representing the best and
      worst performance in each subject. Results revealed complex control strategy,
      with the trunk, shoulder, and elbow playing unique roles in generation of maximal
      hand velocity. The trunk provided a crucial contribution, directly, rotating the
      entire arm, and indirectly, exerting interaction torque that caused swift elbow
      extension. The major role of the shoulder was to transfer the mechanical effect
      of trunk motion to the elbow. However, the shoulder became the primary motion
      generator when the trunk reached its limits of rotation, revealing sequential
      organization of control. The role of the elbow was to maximally comply with
      passive influence of proximal joints. The findings are discussed in light of the
      leading joint hypothesis that offers a straightforward interpretation of control
      of horizontal arm swing as well as practically efficient recommendations for
      increases in movement speed. The revealed role of intersegmental dynamics in
      production of high movement speed suggests that movement slowness characteristic
      for some motor disorders may be partially a compensatory strategy that
      facilitates regulation of interaction torque.

PMID- 19759325
TI  - Generalization of visuomotor learning between bilateral and unilateral
      conditions.
AB  - A long history of behavioral and physiological research has suggested that
      bilateral coordination invokes unique neural processes that are not involved in
      unilateral movements. This hypothesis predicts that motor learning should show
      limited transfer between unilateral and bilateral conditions, which is consistent
      with a recent finding that indicated partial, but not complete, transfer of
      learning between the two conditions. However, during learning of new motor
      skills, transformations must also be made between visual and proprioceptive
      coordinate systems, a process that may occur upstream to the processes that
      differentiate bilateral from unilateral movements. We now investigate whether
      visuomotor adaptations are shared between unilateral and bilateral movement
      conditions. Our results indicate substantial transfer from bilateral to
      subsequent unilateral conditions for both arms. Interestingly, whereas the
      nondominant arm never showed complete adaptation to visual rotation under
      bilateral conditions, this interference, or lack of improvement, in bilateral
      performance did not disturb the visuomotor adaptation process or transfer, as
      reflected by superb unilateral performances immediately following the bilateral
      conditions. These findings unambiguously indicate that visuomotor adaptation can
      extensively generalize between bilateral and unilateral conditions, thus
      suggesting a substantial overlap in the neural processes underlying visuomotor
      transformations between the two movement conditions. Our findings provide support
      for a two-stage model of motor planning, in which the visuomotor transformation
      process precedes the processes that convert the visuomotor plan into effector
      specific commands that incorporate bilateral synergies and that result in the
      forces that determine motion.

PMID- 19759326
TI  - Radial biases in the processing of motion and motion-defined contours by human
      visual cortex.
AB  - Luminance gratings reportedly produce a stronger functional magnetic resonance
      imaging (fMRI) blood oxygen level-dependent (BOLD) signal in those parts of the
      retinotopic cortical maps where they are oriented radially to the point of
      fixation. We sought to extend this finding by examining anisotropies in the
      response of cortical areas V1-V3 to motion-defined contour stimuli. fMRI at 3
      Tesla was used to measure the BOLD signal in the visual cortex of six human
      subjects. Stimuli were composed of strips of spatial white noise texture
      presented in an annular window. The texture in alternate strips moved in opposite
      directions (left-right or up-down). The strips themselves were static and tilted
      45 degrees left or right from vertical. Comparison with maps of the visual field
      obtained from phase-encoded retinotopic analysis revealed systematic patterns of
      radial bias. For motion, a stronger response to horizontal was evident within V1
      and along the borders between V2 and V3. For orientation, the response to
      leftward tilted contours was greater in left dorsal and right ventral V1-V3.
      Radial bias for the orientation of motion-defined contours analogous to that
      reported previously for luminance gratings could reflect cue-invariant processing
      or the operation of distinct mechanisms subject to similar anisotropies in
      orientation tuning. Radial bias for motion might be related to the phenomenon of
      "motion streaks," whereby temporal integration by the visual system introduces
      oriented blur along the axis of motion. We speculate that the observed forms of
      radial bias reflect a common underlying anisotropy in the representation of
      spatiotemporal image structure across the visual field.

PMID- 19759327
TI  - Excitatory and inhibitory synapses in neuropeptide Y-expressing striatal
      interneurons.
AB  - Although rare, interneurons are pivotal in governing striatal output by extensive
      axonal arborizations synapsing on medium spiny neurons. Using a genetically
      modified mouse strain in which a green fluorescent protein (GFP) is driven to be
      expressed under control of the neuropeptide Y (NPY) promoter, we identified NPY
      interneurons and compared them with striatal principal neurons. We found that the
      bacteria artificial chromosome (BAC)-npy mouse expresses GFP with high fidelity
      in the striatum to the endogenous expression of NPY. Patch-clamp analysis from
      NPY neurons showed a heterogeneous population of striatal interneurons. In the
      majority of cells, we observed spontaneous firing of action potentials in
      extracellular recordings. On membrane rupture, most NPY interneurons could be
      classified as low-threshold spiking interneurons and had high-input resistance.
      Voltage-clamp recordings showed that both GABA and glutamate gated ion channels
      mediate synaptic inputs onto these striatal interneurons. AMPA receptor-mediated
      spontaneous excitatory postsynaptic currents (sEPSCs) were small in amplitude and
      infrequent in NPY neurons. Evoked EPSCs did not show short-term plasticity but
      some rectification. Evoked N-methyl-d-aspartate (NMDA) EPSCs had fast decay
      kinetics and were poorly sensitive to an NR2B subunit containing NMDA receptor
      blocker. Spontaneous inhibitory postsynaptic currents (sIPSCs) were mediated by
      GABA(A) receptors and were quite similar among all striatal neurons studied. On
      the contrary, evoked IPSCs decayed faster in NPY neurons than in other striatal
      neurons. These data report for the first time specific properties of synaptic
      transmission to NPY striatal interneurons.

PMID- 19759328
TI  - Locally balanced dendritic integration by short-term synaptic plasticity and
      active dendritic conductances.
AB  - The high degree of variability observed in spike trains and membrane potentials
      of pyramidal neurons in vivo is thought to be a consequence of a balance between
      excitatory and inhibitory inputs, which depends on the dynamics of the network.
      We simulated synaptic currents and ion channels in a reconstructed hippocampal
      CA1 pyramidal cell and show here that a local balance can be achieved on a
      dendritic branch with a different mechanism, based on presynaptic depression of
      quantal release interacting with active dendritic conductances. This mechanism,
      which does not require synaptic inhibition, allows each dendritic branch to
      remain sensitive to correlated synaptic inputs, induces a high degree of
      variability in the output spike train, and can be combined with other balance
      mechanisms based on network dynamics. This hypothesis makes a testable prediction
      for the cause of the observed variability in the firing of hippocampal place
      cells.

PMID- 19759329
TI  - An environmental sensor, TRPV4 is a novel regulator of intracellular Ca2+ in
      human synoviocytes.
AB  - The activation of a vanilloid type 4 transient receptor potential channel (TRPV4)
      has an obligatory role in regulation of intracellular Ca(2+) (Ca(2+)(i)) in
      several types of cells including vascular and sensory organs. In this study, we
      provide evidence that TRPV4 is a functional regulator of Ca(2+)(i) in human
      synoviocytes. Although significant expression of TRPV4 in synoviocytes from
      patients with (RA) and without (CTR) rheumatoid arthritis was detected at mRNA
      and protein level, those in the human fibroblast-like synoviocyte line MH7A were
      rather lower. Consistently, the selective TRPV4 agonist 4alpha-phorbol 12,13
      didecanoate (4alphaPDD) effectively elevated Ca(2+)(i) in the RA and CTR cells,
      which was abolished by the removal of external Ca(2+). Moreover, the elevation
      was inhibited by ruthenium red, a blocker of TRPVs. In MH7A cells transfected
      with human TRPV4 (MH7A-V4), 4alphaPDD elevated the Ca(2+)(i) in a similar manner
      to those in the RA and CTR cells. Electrophysiological analysis also revealed
      that 4alphaPDD activated nonselective cationic currents in RA cells. Application
      of 227 mosM solution to the RA and MH7A-V4 cells elevated their Ca(2+)(i), but
      this does not occur when it was applied to MH7A cells. Treatment of RA but not
      MH7A cells with 4alphaPDD for 24 h reduced their production of IL-8. These
      results suggest that an environmental sensor, TRPV4, is a novel regulator of
      intracellular Ca(2+) in human synoviocytes.

PMID- 19759330
TI  - Molecular regulation of cigarette smoke induced-oxidative stress in human retinal
      pigment epithelial cells: implications for age-related macular degeneration.
AB  - Cigarette smoke is the most important environmental risk factor for developing
      age-related macular degeneration (AMD). Damage to the retinal pigment epithelium
      (RPE) caused by cigarette smoke may underlie the etiology of AMD. This study
      investigated the molecular and cellular effects of cigarette smoke exposure on
      human RPE cells. ARPE-19 or primary human RPE cells were exposed to cigarette
      smoke extract (CSE) or hydroquinone (HQ), a component of cigarette smoke. The
      effect of this exposure on key aspects of RPE vitality including viability, cell
      size, mitochondrial membrane potential (DeltaPsi(m)), superoxide production, 4
      hydroxy-2-nonenal (4-HNE), vascular endothelial growth factor (VEGF), and heme
      oxygenase-1 (HO-1) expression was determined. Exposure of RPE cells to CSE or HQ
      caused oxidative damage and apoptosis, characterized by a reduction in cell size
      and nuclear condensation. Evidence of oxidative damage also included increased
      lipid peroxidation (4-HNE) and mitochondrial superoxide production, as well as a
      decrease in intracellular glutathione (GSH). Exogenous administration of
      antioxidants (GSH and N-acetyl-cysteine) prevented oxidative damage to the RPE
      cells caused by CSE. Cigarette smoke also induced expression of VEGF, HO-1, and
      the transcription factor nuclear factor erythroid-derived 2, like 2 (NRF2).
      However, NRF2 was only modestly involved in CSE-induced HO-1 expression, as shown
      by the NRF2 small interfering RNA studies. These new findings demonstrate that
      cigarette smoke is a potent inducer of oxidative damage and cell death in human
      RPE cells. These data support the hypothesis that cigarette smoke contributes to
      AMD pathogenesis by causing oxidative damage and cell death to RPE cells.

PMID- 19759331
TI  - Myostatin inhibits IGF-I-induced myotube hypertrophy through Akt.
AB  - Myostatin is a highly conserved negative regulator of skeletal muscle growth.
      Loss of functional myostatin in cattle, mice, sheep, dogs, and humans results in
      increased muscle mass. The molecular mechanisms responsible for this increase in
      muscle growth are not fully understood. Previously, we have reported that
      phenylephrine-induced cardiac muscle growth and Akt activation are enhanced in
      myostatin knockout mice compared with controls. Here we report that skeletal
      muscle from myostatin knockout mice show increased Akt protein expression and
      overall activity at baseline secondary to an increase in Akt mRNA. We examined
      the functional role of myostatin modulation of Akt in C2C12 myotubes, a well
      established in vitro model of skeletal muscle hypertrophy. Adenoviral
      overexpression of myostatin attenuated the insulin-like growth factor-I (IGF-I)
      mediated increase in myotube diameter, as well as IGF-I-stimulated Akt
      phosphorylation. Inhibition of myostatin by overexpression of the NH(2)-terminal
      portion of myostatin was sufficient to increase myotube diameter and Akt
      phosphorylation. Coexpression of myostatin and constitutively active Akt (myr
      Akt) restored the increase in myotube diameter. Conversely, expression of
      dominant negative Akt (dn-Akt) with the inhibitory myostatin propeptide blocked
      the increase in myotube diameter. Of note, ribosomal protein S6 phosphorylation
      and atrogin-1/muscle atrophy F box mRNA were increased in skeletal muscle from
      myostain knockout mice. Together, these data suggest myostatin regulates muscle
      growth at least in part through regulation of Akt.

PMID- 19759332
TI  - Selective and specific regulation of ectodomain shedding of angiotensin
      converting enzyme 2 by tumor necrosis factor alpha-converting enzyme.
AB  - Angiotensin-converting enzyme 2 (ACE2) is a newly identified regulator of the
      renin-angiotensin system. This type I membrane-anchored protein has a
      catalytically active ectodomain that undergoes shedding. Tumor necrosis factor
      alpha-converting enzyme (TACE) has been shown to be involved in ACE2 shedding.
      Although pathophysiological significance of ACE2 shedding has been suggested,
      regulation of this process by TACE is not clearly defined. We characterized TACE
      mediated constitutive ectodomain shedding of ACE2 using wild-type Chinese Hamster
      Ovary (WT-CHO), the TACE-mutant M2 (M2-CHO) cells, and EC-4 and EC-2 cells that
      are fibroblasts from wild-type and TACE-null mice, respectively. ACE2 was
      constitutively cleaved to release two distinct major soluble forms. The
      deglycosylated molecular masses of the larger (LSF) and smaller soluble form
      (SSF) were approximately 80 and 70 kDa, respectively. These forms had equivalent
      enzyme activities. Reduced shedding for the LSF from M2-CHO and EC-2 cells when
      compared with WT-CHO and EC-4 cells, respectively, was noted. TACE reconstitution
      in EC-2 cells expressing ACE2 resulted in increase in LSF but not SSF release,
      demonstrating a main role of TACE in LSF release and distinct regulations of
      release of the two soluble forms. Deletions of the juxtamembrane region of ACE2
      reduced LSF release in CHO cell lines, whereas it abolished TACE-induced shedding
      in EC-2 cells. Analysis of TACE structural domains confirmed that the active site
      in the catalytic domain is essential for ACE2 shedding but that noncatalytic
      domains also play additional roles. These results demonstrate selective and
      specific regulation of constitutive shedding of ACE2 by TACE.

PMID- 19759333
TI  - Peripheral osmotic stimulation inhibits the brain's innate immune response to
      microdialysis of acidic perfusion fluid adjacent to supraoptic nucleus.
AB  - During the brain's innate immune response microglia, astroglia and ependymal
      cells resolve/repair damaged tissue and control infection. Released interleukin
      1beta (IL-1beta) reaching cerebroventricles stimulates circumventricular organs
      (CVOs; subfornical organ, SFO; organum vasculosum lamina terminalis, OVLT), the
      median preoptic nucleus (MePO), and magnocellular and parvocellular neurons in
      the supraoptic (SON) and paraventricular (PVN) nuclei. Hypertonic saline (HS)
      also activates these osmosensory CVOs and neuroendocrine systems, but, in
      contrast to IL-1beta, inhibits the peripheral immune response. To examine whether
      the brain's innate immune response is attenuated by osmotic stimulation, sterile
      acidic perfusion fluid was microdialyzed (2 microl/min) in the SON area of
      conscious rats for 6 h with sterile HS (1.5 M NaCl) injected subcutaneously (15
      ml/kg) at 5 h. Immunohistochemistry identified cytokine sources (IL-1beta(+); OX
      42(+) microglia) and targets (IL-1R(+); inducible cyclooxygenase, COX-2(+); c
      Fos(+)) near the probe, in CVOs, MePO, ependymal cells, periventricular
      hypothalamus, SON, and PVN. Inserting the probe stimulated magnocellular neurons
      (c-Fos(+); SON; PVN) via the MePO (c-Fos(+)), a response enhanced by HS.
      Microdialysis activated microglia (OX-42(+); amoeboid/hypertrophied; IL-1beta(+))
      in the adjacent SON and bilaterally in perivascular areas of the PVN,
      periventricular hypothalamus and ependyma, coincident with c-Fos expression in
      ependymal cells and COX-2 in the vasculature. These microglial responses were
      attenuated by HS, coincident with activating parvocellular and magnocellular
      neuroendocrine systems and elevating circulating IL-1beta, oxytocin, and
      vasopressin. Acidosis-induced cellular injury from microdialysis activated the
      brain's innate immune response by a mechanism inhibited by peripheral osmotic
      stimulation.

PMID- 19759334
TI  - Inhibition of biliverdin reductase increases ANG II-dependent superoxide levels
      in cultured renal tubular epithelial cells.
AB  - Induction of heme oxygenase-1 (HO-1) in the renal medulla increases carbon
      monoxide and bilirubin production and decreases ANG II-mediated superoxide
      production. The goal of this study was to determine the importance of increases
      in bilirubin to the antioxidant effects of HO-1 induction in cultured mouse thick
      ascending loop of Henle (TALH) and inner medullary collecting duct (IMCD3) cells.
      Bilirubin levels were decreased by using small interfering RNAs (siRNAs) targeted
      to biliverdin reductase (BVR), which is the cellular enzyme responsible for the
      conversion of biliverdin to bilirubin. Treatment of cultured TALH or IMCD-3 cells
      with BVR siRNA (50 or 100 nM) resulted in an 80% decrease in the level of BVR
      protein and decreased cellular bilirubin levels from 46 +/- 5 to 23 +/- 4 nM (n =
      4). We then determined the effects of inhibition of BVR on ANG II-mediated
      superoxide production. Superoxide production induced by ANG II (10(-9) M)
      significantly increased in both TALH and IMCD-3 cells. Treatment of TALH cells
      with BVR siRNA resulted in a significant increase in ouabain-sensitive rubidium
      uptake from 95 +/- 6 to 122 +/- 5% control (n = 4, P < 0.05). Lastly, inhibition
      of BVR with siRNA did not prevent the decrease in superoxide levels observed in
      cells pretreated with the HO-1 inducer, hemin. We conclude that decreased levels
      of cellular bilirubin increase ANG II-mediated superoxide production and sodium
      transport; however, increases in bilirubin are not necessary for HO-1 induction
      to attenuate ANG II-mediated superoxide production.

PMID- 19759335
TI  - Ischemia-induced brain damage is enhanced in human renin and angiotensinogen
      double-transgenic mice.
AB  - To investigate the role of brain angiotensin II (ANG II) in the pathogenesis of
      injury following ischemic stroke, mice overexpressing renin and angiotensinogen
      (R+A+) and their wild-type control animals (R-A-) were used for experimental
      ischemia studies. Focal brain ischemia was induced by middle cerebral artery
      occlusion (MCAO). The severity of ischemic injury was determined by measuring
      neurological deficits and histological damage at 24 and 48 h after MCAO,
      respectively. To exclude the influence of blood pressure and local collateral
      blood flow, brain slices were used for oxygen and glucose deprivation (OGD)
      studies. The severity of OGD-induced damage was determined by measuring
      indicators of tissue swelling and cell death, the intensity of the intrinsic
      optical signal (IOS), and the number of propidium iodide (PI) staining cells,
      respectively. Results showed 1) R+A+ mice showed higher neurological deficit
      score (3.8 +/- 0.5 and 2.5 +/- 0.3 for R+A+ and R-A-, respectively, P < 0.01) and
      larger infarct volume (22.2 +/- 1.6% and 14.1 +/- 1.2% for R+A+ and R-A-,
      respectively, P < 0.01); 2) The R+A+ brain slices showed more severe tissue
      swelling and cell death in the cortex (IOS: 140 +/- 6% and 114 +/- 10%; PI: 139
      +/- 20 cells/field and 39 +/- 9 cells/field for R+A+ and R-A-, respectively, P <
      0.01); 3) treatment with losartan (20 micromol/l) abolished OGD-induced
      exaggeration of cell injury seen in R+A+ mice. The data indicate that activation
      of ANG II/AT(1) signaling is harmful to brain exposed to ischemia.

PMID- 19759337
TI  - Maternal low-protein diet alters pancreatic islet mitochondrial function in a sex
      specific manner in the adult rat.
AB  - Mitochondrial dysfunction may be a long-term consequence of a poor nutritional
      environment during early life. Our aim was to investigate whether a maternal low
      protein (LP) diet may program mitochondrial dysfunction in islets of adult
      progeny before glucose intolerance ensues. To address this, pregnant Wistar rats
      were fed isocaloric diets containing either 20% protein (control) or 8% protein
      (LP diet) throughout gestation. From birth, offspring received the control diet.
      The mitochondrial function was analyzed in islets of 3-mo-old offspring. Related
      to their basal insulin release, cultured islets from both male and female LP
      offspring presented a lower response to glucose challenge and a blunted ATP
      production compared with control offspring. The expression of malate
      dehydrogenase as well as the subunit 6 of the ATP synthase encoded by
      mitochondrial genome (mtDNA) was lower in these islets, reducing the capacity of
      ATP production through the Krebs cycle and oxidative phosphorylation. However,
      mtDNA content was unchanged in LP islets compared with control. Several
      consequences of protein restriction during fetal life were more marked in male
      offspring. Only LP males showed an increased reactive oxygen species production
      associated with a higher expression of mitochondrial subunits of the electron
      transport chain NADH-ubiquinone oxireductase subunit 4L, an overexpression of
      peroxisome proliferator-activated receptor-gamma and uncoupling protein-2, and a
      strongly reduced beta-cell mass. In conclusion, mitochondrial function is clearly
      altered in islets from LP adult offspring in a sex-specific manner. That may
      provide a cellular explanation for the earlier development of glucose intolerance
      in male than in female offspring of dams fed an LP diet.

PMID- 19759336
TI  - Mice lacking the G protein gamma3-subunit show resistance to opioids and diet
      induced obesity.
AB  - Contributing to the obesity epidemic, there is increasing evidence that
      overconsumption of high-fat foods may be analogous to drug addiction in that the
      palatability of these foods is associated with activation of specific reward
      pathways in the brain. With this perspective, we report that mice lacking the G
      protein gamma(3)-subunit (Gng3(-/-) mice) show resistance to high-fat diet
      induced weight gain over the course of a 12-wk study. Compared with Gng3(+/+)
      controls, female Gng3(-/-) mice exhibit a 40% reduction in weight gain and a 53%
      decrease in fat pad mass, whereas male Gng3(-/-) mice display an 18% reduction in
      weight gain and no significant decrease in fat pad mass. The basis for the
      lowered weight gain is related to reduced food consumption for female and male
      Gng3(-/-) mice of 13% and 14%, respectively. Female Gng3(-/-) mice also show a
      lesser preference for high-fat chow than their female Gng3(+/+) littermates,
      suggesting an attenuated effect on a reward pathway associated with
      overconsumption of fat. One possible candidate is the micro-opioid receptor
      (Oprm1) signaling cascade. Supporting a defect in this signaling pathway, Gng3(-/
      ) mice show marked reductions in both acute and chronic morphine responsiveness,
      as well as increases in endogenous opioid mRNA levels in reward-related regions
      of the brain. Taken together, these data suggest that the decreased weight gain
      of Gng3(-/-) mice may be related to a reduced rewarding effect of the high-fat
      diet resulting from a defect in Oprm1 signaling and loss of the G protein
      gamma(3)-subunit.

PMID- 19759338
TI  - Intramuscular VEGF repairs the failing heart: role of host-derived growth factors
      and mobilization of progenitor cells.
AB  - Skeletal muscle produces a myriad of mitogenic factors possessing cardiovascular
      regulatory effects that can be explored for cardiac repair. Given the reported
      findings that VEGF may modulate muscle regeneration, we investigated the
      therapeutic effects of chronic injections of low doses of human recombinant VEGF
      A(165) (0.1-1 microg/kg) into the dystrophic hamstring muscle in a hereditary
      hamster model of heart failure and muscular dystrophy. In vitro, VEGF stimulated
      proliferation, migration, and growth factor production of cultured C2C12 skeletal
      myocytes. VEGF also induced production of HGF, IGF2, and VEGF by skeletal muscle.
      Analysis of skeletal muscle revealed an increase in myocyte nuclear [531 +/- 12
      VEGF 1 microg/kg vs. 364 +/- 19 for saline (number/mm(2)) saline] and capillary
      [591 +/- 80 VEGF 1 microg/kg vs. 342 +/- 21 for saline (number/mm(2))] densities.
      Skeletal muscle analysis revealed an increase in Ki67(+) nuclei in the VEGF 1
      microg/kg group compared with saline. In addition, VEGF mobilized c-kit(+),
      CD31(+), and CXCR4(+) progenitor cells. Mobilization of progenitor cells was
      consistent with higher SDF-1 concentrations found in hamstring, plasma, and heart
      in the VEGF group. Echocardiogram analysis demonstrated improvement in left
      ventricular ejection fraction (0.60 +/- 0.02 VEGF 1 microg/kg vs. 0.45 +/- 0.01
      mm for saline) and an attenuation in ventricular dilation [5.59 +/- 0.12 VEGF 1
      microg/kg vs. 6.03 +/- 0.09 for saline (mm)] 5 wk after initiating therapy.
      Hearts exhibited higher cardiomyocyte nuclear [845 +/- 22 VEGF 1 microg/kg vs.
      519 +/- 40 for saline (number/mm(2))] and capillary [2,159 +/- 119 VEGF 1
      microg/kg vs. 1,590 +/- 66 for saline (number/mm(2))] densities. Myocardial
      analysis revealed approximately 2.5 fold increase in Ki67+ cells and
      approximately 2.8-fold increase in c-kit(+) cells in the VEGF group, which
      provides evidence for cardiomyocyte regeneration and progenitor cell expansion.
      This study provides novel evidence of a salutary effect of VEGF in the
      cardiomyopathic hamster via induction of myogenic growth factor production by
      skeletal muscle and mobilization of progenitor cells, which resulted in
      attenuation of cardiomyopathy and repair of the heart.

PMID- 19759339
TI  - Functional analysis of alpha-DOX2, an active alpha-dioxygenase critical for
      normal development in tomato plants.
AB  - Plant alpha-dioxygenases initiate the synthesis of oxylipins by catalyzing the
      incorporation of molecular oxygen at the alpha-methylene carbon atom of fatty
      acids. Previously, alpha-DOX1 has been shown to display alpha-dioxygenase
      activity and to be implicated in plant defense. In this study, we investigated
      the function of a second alpha-dioxygenase isoform, alpha-DOX2, in tomato
      (Solanum lycopersicum) and Arabidopsis (Arabidopsis thaliana). Recombinant
      Slalpha-DOX2 and Atalpha-DOX2 proteins catalyzed the conversion of a wide range
      of fatty acids into 2(R)-hydroperoxy derivatives. Expression of Slalpha-DOX2 and
      Atalpha-DOX2 was found in seedlings and increased during senescence induced by
      detachment of leaves. In contrast, microbial infection, earlier known to increase
      the expression of alpha-DOX1, did not alter the expression of Slalpha-DOX2 or
      Atalpha-DOX2. The tomato mutant divaricata, characterized by early dwarfing and
      anthocyanin accumulation, carries a mutation at the Slalpha-DOX2 locus and was
      chosen for functional studies of alpha-DOX2. Transcriptional changes in such
      mutants showed the up-regulation of genes playing roles in lipid and
      phenylpropanoid metabolism, the latter being in consonance with the anthocyanin
      accumulation. Transgenic expression of Atalpha-DOX2 and Slalpha-DOX2 in
      divaricata partially complemented the compromised phenotype in mature plants and
      fully complemented it in seedlings, thus indicating the functional
      exchangeability between alpha-DOX2 from tomato and Arabidopsis. However, deletion
      of Atalpha-DOX2 in Arabidopsis plants did not provoke any visible phenotypic
      alteration indicating that the relative importance of alpha-DOX2 in plant
      physiology is species specific.

PMID- 19759340
TI  - Characterization of the entire cystatin gene family in barley and their target
      cathepsin L-like cysteine-proteases, partners in the hordein mobilization during
      seed germination.
AB  - Plant cystatins are inhibitors of cysteine-proteases of the papain C1A and
      legumain C13 families. Cystatin data from multiple plant species have suggested
      that these inhibitors act as defense proteins against pests and pathogens and as
      regulators of protein turnover. In this study, we characterize the entire
      cystatin gene family from barley (Hordeum vulgare), which contain 13 nonredundant
      genes, and identify and characterize their target enzymes, the barley cathepsin L
      like proteases. Cystatins and proteases were expressed and purified from
      Escherichia coli cultures. Each cystatin was found to have different inhibitory
      capability against barley cysteine-proteases in in vitro inhibitory assays using
      specific substrates. Real-time reverse transcription-polymerase chain reaction
      revealed that inhibitors and enzymes present a wide variation in their messenger
      RNA expression patterns. Their transcripts were mainly detected in developing and
      germinating seeds, and some of them were also expressed in leaves and roots.
      Subcellular localization of cystatins and cathepsin L-like proteases fused to
      green fluorescent protein demonstrated the presence of both protein families
      throughout the endoplasmic reticulum and the Golgi complex. Proteases and
      cystatins not only colocalized but also interacted in vivo in the plant cell, as
      revealed by bimolecular fluorescence complementation. The functional relationship
      between cystatins and cathepsin L-like proteases was inferred from their common
      implication as counterparts of mobilization of storage proteins upon barley seed
      germination. The opposite pattern of transcription expression in gibberellin
      treated aleurones presented by inhibitors and enzymes allowed proteases to
      specifically degrade B, C, and D hordeins stored in the endosperm of barley
      seeds.

PMID- 19759341
TI  - Identification of an Arabidopsis feruloyl-coenzyme A transferase required for
      suberin synthesis.
AB  - All plants produce suberin, a lipophilic barrier of the cell wall that controls
      water and solute fluxes and restricts pathogen infection. It is often described
      as a heteropolymer comprised of polyaliphatic and polyaromatic domains. Major
      monomers include omega-hydroxy and alpha,omega-dicarboxylic fatty acids,
      glycerol, and ferulate. No genes have yet been identified for the aromatic
      suberin pathway. Here we demonstrate that Arabidopsis (Arabidopsis thaliana) gene
      AT5G41040, a member of the BAHD family of acyltransferases, is essential for
      incorporation of ferulate into suberin. In Arabidopsis plants transformed with
      the AT5G41040 promoter:YFP fusion, reporter expression is localized to cell
      layers undergoing suberization. Knockout mutants of AT5G41040 show almost
      complete elimination of suberin-associated ester-linked ferulate. However, the
      classic lamellar structure of suberin in root periderm of at5g41040 is not
      disrupted. The reduction in ferulate in at5g41040-knockout seeds is associated
      with an approximate stoichiometric decrease in aliphatic monomers containing
      omega-hydroxyl groups. Recombinant AT5G41040p catalyzed acyl transfer from
      feruloyl-coenzyme A to omega-hydroxyfatty acids and fatty alcohols, demonstrating
      that the gene encodes a feruloyl transferase. CYP86B1, a cytochrome P450
      monooxygenase gene whose transcript levels correlate with AT5G41040 expression,
      was also investigated. Knockouts and overexpression confirmed CYP86B1 as an
      oxidase required for the biosynthesis of very-long-chain saturated alpha,omega
      bifunctional aliphatic monomers in suberin. The seed suberin composition of
      cyp86b1 knockout was surprisingly dominated by unsubstituted fatty acids that are
      incapable of polymeric linkages. Together, these results challenge our current
      view of suberin structure by questioning both the function of ester-linked
      ferulate as an essential component and the existence of an extended aliphatic
      polyester.

PMID- 19759342
TI  - A systems-level analysis of the effects of light quality on the metabolism of a
      cyanobacterium.
AB  - Photosynthetic organisms experience changes in light quantity and light quality
      in their natural habitat. In response to changes in light quality, these
      organisms redistribute excitation energy and adjust photosystem stoichiometry to
      maximize the utilization of available light energy. However, the response of
      other cellular processes to changes in light quality is mostly unknown. Here, we
      report a systematic investigation into the adaptation of cellular processes in
      Synechocystis species PCC 6803 to light that preferentially excites either
      photosystem II or photosystem I. We find that preferential excitation of
      photosystem II and photosystem I induces massive reprogramming of the
      Synechocystis transcriptome. The rewiring of cellular processes begins as soon as
      Synechocystis senses the imbalance in the excitation of reaction centers. We find
      that Synechocystis utilizes the cyclic photosynthetic electron transport chain
      for ATP generation and a major part of the respiratory pathway to generate
      reducing equivalents and carbon skeletons during preferential excitation of
      photosystem I. In contrast, cytochrome c oxidase and photosystem I act as
      terminal components of the photosynthetic electron transport chain to produce
      sufficient ATP and limited amounts of NADPH and reduced ferredoxin during
      preferential excitation of photosystem II. To overcome the shortage of NADPH and
      reduced ferredoxin, Synechocystis preferentially activates transporters and
      acquisition pathways to assimilate ammonia, urea, and arginine over nitrate as a
      nitrogen source. This study provides a systematic analysis of cellular processes
      in cyanobacteria in response to preferential excitation and shows that the
      cyanobacterial cell undergoes significant adjustment of cellular processes, many
      of which were previously unknown.

PMID- 19759343
TI  - A nuclear factor regulates abscisic acid responses in Arabidopsis.
AB  - Abscisic acid (ABA) is a plant hormone that regulates plant growth as well as
      stress responses. In this study, we identified and characterized a new
      Arabidopsis (Arabidopsis thaliana) protein, Nuclear Protein X1 (NPX1), which was
      up-regulated by stress and treatment with exogenous ABA. Stomatal closure, seed
      germination, and primary root growth are well-known ABA responses that were less
      sensitive to ABA in NPX1-overexpressing plants. NPX1-overexpressing plants were
      more drought sensitive, and the changes in response to drought were due to the
      altered guard cell sensitivity to ABA in transgenic plants and not to a lack of
      ABA production. The nuclear localization of NPX1 correlated with changes in the
      expression of genes involved in ABA biosynthesis and ABA signal transduction. To
      understand the function of NPX1, we searched for interacting proteins and found
      that an ABA-inducible NAC transcription factor, TIP, interacted with NPX1. Based
      on the whole plant phenotypes, we hypothesized that NPX1 acts as a
      transcriptional repressor, and this was demonstrated in yeast, where we showed
      that TIP was repressed by NPX1. Our results indicate that the previously unknown
      protein NPX1 acts as a negative regulator in plant response to changes in
      environmental conditions through the control of ABA-regulated gene expression.
      The characterization of this factor enhances our understanding of guard cell
      function and the mechanisms that plants use to modulate water loss from leaves
      under drought conditions.

PMID- 19759344
TI  - Three sequenced legume genomes and many crop species: rich opportunities for
      translational genomics.

PMID- 19759345
TI  - Starch synthesis in Arabidopsis is achieved by spatial cotranscription of core
      starch metabolism genes.
AB  - Starch synthesis and degradation require the participation of many enzymes, occur
      in both photosynthetic and nonphotosynthetic tissues, and are subject to
      environmental and developmental regulation. We examine the distribution of starch
      in vegetative tissues of Arabidopsis (Arabidopsis thaliana) and the expression of
      genes encoding core enzymes for starch synthesis. Starch is accumulated in
      plastids of epidermal, mesophyll, vascular, and root cap cells but not in root
      proper cells. We also identify cells that can synthesize starch heterotrophically
      in albino mutants. Starch synthesis in leaves is regulated by developmental stage
      and light. Expression of gene promoter-beta-glucuronidase fusion constructs in
      transgenic seedlings shows that starch synthesis genes are transcriptionally
      active in cells with starch synthesis and are inactive in root proper cells
      except the plastidial phosphoglucose isomerase. In addition, ADG2 (for ADPG
      PYROPHOSPHORYLASE2) is not required for starch synthesis in root cap cells.
      Expression profile analysis reveals that starch metabolism genes can be clustered
      into two sets based on their tissue-specific expression patterns. Starch
      distribution and expression pattern of core starch synthesis genes are common in
      Arabidopsis and rice (Oryza sativa), suggesting that the regulatory mechanism for
      starch metabolism genes may be conserved evolutionarily. We conclude that starch
      synthesis in Arabidopsis is achieved by spatial coexpression of core starch
      metabolism genes regulated by their promoter activities and is fine-tuned by cell
      specific endogenous and environmental controls.

PMID- 19759346
TI  - Deletion-based reverse genetics in Medicago truncatula.
AB  - The primary goal of reverse genetics, the identification of null mutations in
      targeted genes, is achieved through screening large populations of randomly
      mutagenized plants. T-DNA and transposon-based mutagenesis has been widely
      employed but is limited to species in which transformation and tissue culture are
      efficient. In other species, TILLING (for Targeting Induced Local Lesions IN
      Genomes), based on chemical mutagenesis, has provided an efficient method for the
      identification of single base pair mutations, only 5% of which will be null
      mutations. Furthermore, the efficiency of inducing point mutations, like
      insertion-based mutations, is dependent on target size. Here, we describe an
      alternative reverse genetic strategy based on physically induced genomic
      deletions that, independent of target size, exclusively recovers knockout
      mutants. Deletion TILLING (De-TILLING) employs fast neutron mutagenesis and a
      sensitive polymerase chain reaction-based detection. A population of 156,000
      Medicago truncatula plants has been structured as 13 towers each representing
      12,000 M2 plants. The De-TILLING strategy allows a single tower to be screened
      using just four polymerase chain reaction reactions. Dual screening and three
      dimensional pooling allows efficient location of mutants from within the towers.
      With this method, we have demonstrated the detection of mutants from this
      population at a rate of 29% using five targets per gene. This De-TILLING reverse
      genetic strategy is independent of tissue culture and efficient plant
      transformation and therefore applicable to any plant species. De-TILLING mutants
      offer advantages for crop improvement as they possess relatively few background
      mutations and no exogenous DNA.

PMID- 19759347
TI  - Stable transcription activities dependent on an orientation of Tam3 transposon
      insertions into Antirrhinum and yeast promoters occur only within chromatin.
AB  - Transposon insertions occasionally occur in the promoter regions of plant genes,
      many of which are still capable of being transcribed. However, it remains unclear
      how transcription of such promoters is able to occur. Insertion of the Tam3
      transposon into various genes of Antirrhinum majus can confer leaky phenotypes
      without its excision. These genes, named Tam3-permissible alleles, often contain
      Tam3 in their promoter regions. Two alleles at different anthocyanin biosynthesis
      loci, nivea(recurrensTam3) (niv(rec)) and pallida(recurrensTam3) (pal(rec)), both
      contain Tam3 at a similar position immediately upstream of the promoter TATA-box;
      however, these insertions had different phenotypic consequences. Under conditions
      where the inserted Tam3 is immobilized, the niv(rec) line produces pale red
      petals, whereas the pal(rec) line produces no pigment. These pigmentation
      patterns are correlated with the level of transcripts from the niv(rec) or
      pal(rec) alleles, and these transcriptional activities are independent of DNA
      methylation in their promoter regions. In niv(rec), Tam3 is inserted in an
      orientation that results in the 3' end of Tam3 adjacent to the 5' region of the
      gene coding sequence. In contrast, the pal(rec) allele contains a Tam3 insertion
      in the opposite orientation. Four of five different nonrelated genes that are
      also Tam3-permissible alleles and contain Tam3 within the promoter region share
      the same Tam3 orientation as niv(rec). The different transcriptional activities
      dependent on Tam3 orientation in the Antirrhinum promoters were consistent with
      expression of luciferase reporter constructs introduced into yeast chromosomes
      but not with transient expression of these constructs in Antirrhinum cells. These
      results suggest that for Tam3 to sustain stable transcriptional activity in
      various promoters it must be embedded in chromatin.

PMID- 19759348
TI  - Miniature1-encoded cell wall invertase is essential for assembly and function of
      wall-in-growth in the maize endosperm transfer cell.
AB  - The miniature1 (mn1) seed phenotype in maize (Zea mays) is due to a loss-of
      function mutation at the Mn1 locus that encodes a cell wall invertase (INCW2)
      that localizes exclusively to the basal endosperm transfer cells (BETCs) of
      developing seeds. A common feature of all transfer cells is the labyrinth-like
      wall-in-growth (WIG) that increases the plasma membrane area, thereby enhancing
      transport capacity in these cells. To better understand WIG formation and roles
      of INCW2 in the BETC development, we examined wild-type and mn1 mutant developing
      kernels by cryofixation and electron microscopy. In Mn1 seeds, WIGs developed
      uniformly in the BETC layer during 7 to 17 d after pollination, and the
      secretory/endocytic organelles proliferated in the BETCs. Mitochondria
      accumulated in the vicinity of WIGs, suggesting a functional link between them.
      In the mn1 BETCs, WIGs were stunted and their endoplasmic reticulum was swollen;
      Golgi density in the mutant BETCs was 51% of the Mn1 Golgi density. However, the
      polarized distribution of mitochondria was not affected. INCW2-specific
      immunogold particles were detected in WIGs, the endoplasmic reticulum, Golgi
      stacks, and the trans-Golgi network in the Mn1 BETCs, while immunogold particles
      were extremely rare in the mutant BETCs. Levels of WIG development in the empty
      pericarp4 mutant was heterogeneous among BETCs, and INCW2 immunogold particles
      were approximately four times more abundant in the larger WIGs than in the
      stunted WIGs. These results indicate that polarized secretion is activated during
      WIG formation and that INCW2 is required for normal development of WIGs to which
      INCW2 is localized.

PMID- 19759349
TI  - Guidelines for establishing a donor human milk depot.
AB  - Human milk is the preferred choice for infant feeding. When a sick or premature
      infant's own mother's milk is unavailable, donor human milk is becoming more
      widely used. Many potential milk donors do not live within close proximity to the
      10 North American not-for-profit milk banks. Transporting milk via commercial
      carriers can be inconvenient and costly for recipient banks. A network of donor
      human milk depots is one practical way to increase the quantity of available
      donor human milk. This article provides guidelines and practical suggestions for
      establishing a donor human milk depot.

PMID- 19759350
TI  - Evaluation of a breastfeeding assessment score in a diverse population.
AB  - A previous study performed in a predominately suburban population developed a
      breastfeeding assessment score (BAS) that was designed to predict, prior to
      hospital discharge, those mothers who would discontinue breastfeeding within the
      first 10 days of age. The purpose of the present study was to assess the BAS in a
      more diverse population. Patients were solicited from 3 urban hospitals serving
      patients primarily supported by public funding. Results of the present study with
      1182 mother-infant pairs confirmed that 5 variables scored on a 0-2 scale
      (maternal age, previous breastfeeding experience, latching difficulty,
      breastfeeding interval, number bottles) remained highly significant for
      predicting discontinuation of breastfeeding. The data also demonstrate that the
      BAS is inversely related to the risk of cessation of breastfeeding at 7 to 10
      days of age. Those at an early risk of cessation of breastfeeding, identified by
      the BAS, may benefit from early identification and a lactation consultation.

PMID- 19759351
TI  - Formula feeding is associated with increased hospital admissions due to
      infections among infants younger than 6 months in Manila, Philippines.
AB  - This case control study evaluates the association between hospitalization due to
      infection and feeding practices among infants aged >or= 3 days to < 6 months.
      Mothers of 191 cases hospitalized for infections and 208 healthy controls were
      interviewed using a standardized questionnaire documenting infant-feeding
      history. Results given in odds ratio and 95% confidence intervals (OR, 95% CI)
      were adjusted for age, education, and place of delivery. Exclusively formula-fed
      infants were more likely to be hospitalized for any infection (3.7, 1.8-7.5),
      pneumonia (3.0, 1.2-7.4), and diarrhea (10.5, 2.5-41.9) compared to exclusively
      breastfed infants. Infants who did not receive any breast milk were more likely
      to be hospitalized for any infection (3.5, 2.1-5.9), neonatal sepsis (4.9, 1.3
      18.3), pneumonia (2.8, 1.5-5.4), and diarrhea (19.6, 6.5-58.6) than infants who
      received any breast milk. This study showed a strong positive association between
      the intake of formula and/or nonbreast milk supplements and the risk of
      hospitalization for infectious causes.

PMID- 19759352
TI  - Frozen breast milk at -20 degrees C and -80 degrees C: a longitudinal study of
      glutathione peroxidase activity and malondialdehyde concentration.
AB  - When breast milk extraction and storage is required before ingestion, it is
      important to establish the conditions that ensure the least losses in milk
      quality, like the antioxidant capacity. The present study evaluates glutathione
      peroxidase activity and malondialdehyde concentration of breast milk when stored
      frozen, comparing the effects of 2 temperatures (-20 degrees C and -80 degrees C)
      and different storage times (15, 30, and 60 days). The results indicate that
      freezing induces losses in the antioxidant properties of breast milk and that
      such losses increase with the duration of storage and differ in intensity
      according to the temperature. It is concluded that to maximally preserve the
      antioxidant properties of breast milk, it is advisable to store the latter at -80
      degrees C for a period of less than 30 days, rather than for shorter time periods
      at the usual temperature of -20 degrees C.

PMID- 19759353
TI  - Transfer of metyrapone and its metabolite, rac-metyrapol, into breast milk.
AB  - Metyrapone, an inhibitor of corticosteroid biosynthesis, is used in the diagnosis
      and treatment of adrenocortical hyperfunction. The authors describe the excretion
      of metyrapone and its metabolite, rac-metyrapol, in milk from a lactating woman
      requiring metyrapone treatment (250 mg 4 times daily). At steady state, the
      average concentrations in milk and absolute and relative infant doses were 11
      microg/L, 1.7 microg/kg/d, and 0.02%, respectively, for metyrapone, and 48.5
      microg/L, 7.3 microg/kg/d, and 0.08%, respectively, for rac-metyrapol. The
      findings suggest that maternal metyrapone use during breastfeeding is extremely
      unlikely to be a significant risk for the breastfed infant.

PMID- 19759354
TI  - Quantification of Gi-mediated inhibition of adenylyl cyclase activity reveals
      that UDP is a potent agonist of the human P2Y14 receptor.
AB  - The P2Y14 receptor was initially identified as a G protein-coupled receptor
      activated by UDP-glucose and other nucleotide sugars. We have developed several
      cell lines that stably express the human P2Y14 receptor, allowing facile
      examination of its coupling to native Gi family G proteins and their associated
      downstream signaling pathways (J Pharmacol Exp Ther 330:162-168, 2009). In the
      current study, we examined P2Y14 receptor-dependent inhibition of cyclic AMP
      accumulation in human embryonic kidney (HEK) 293, C6 glioma, and Chinese hamster
      ovary (CHO) cells stably expressing this receptor. Not only was the human P2Y14
      receptor activated by UDP-glucose, but it also was activated by UDP. The apparent
      efficacies of UDP and UDP-glucose were similar, and the EC50 values (74, 33, and
      29 nM) for UDP-dependent activation of the P2Y14 receptor in HEK293, CHO, and C6
      glioma cells, respectively, were similar to the EC50 values (323, 132, and 72 nM)
      observed for UDP-glucose. UDP and UDP-glucose also stimulated extracellular
      signal-regulated kinase (ERK) 1/2 phosphorylation in P2Y14 receptor-expressing
      HEK293 cells but not in wild-type HEK293 cells. A series of analogs of UDP were
      potent P2Y14 receptor agonists, but the naturally occurring nucleoside
      diphosphates, CDP, GDP, and ADP exhibited agonist potencies over 100-fold less
      than that observed with UDP. Two UDP analogs were identified that selectively
      activate the P2Y14 receptor over the UDP-activated P2Y6 receptor, and these
      molecules stimulated phosphorylation of ERK1/2 in differentiated human HL-60
      promyeloleukemia cells, which natively express the P2Y14 receptor but had no
      effect in wild-type HL-60 cells, which do not express the receptor. We conclude
      that UDP is an important cognate agonist of the human P2Y14 receptor.

PMID- 19759355
TI  - Stage-specific Arf tumor suppression in Notch1-induced T-cell acute lymphoblastic
      leukemia.
AB  - Frequent hallmarks of T-cell acute lymphoblastic leukemia (T-ALL) include
      aberrant NOTCH signaling and deletion of the CDKN2A locus, which contains 2
      closely linked tumor suppressor genes (INK4A and ARF). When bone marrow cells or
      thymocytes transduced with a vector encoding the constitutively activated
      intracellular domain of Notch1 (ICN1) are expanded ex vivo under conditions that
      support T-cell development, cultured progenitors rapidly induce CD4+/CD8+ T-ALLs
      after infusion into healthy syngeneic mice. Under these conditions, enforced ICN1
      expression also drives formation of T-ALLs in unconditioned CD-1 nude mice,
      bypassing any requirements for thymic maturation. Retention of Arf had relatively
      modest activity in suppressing the formation of T-ALLs arising from bone marrow
      derived ICN1+ progenitors in which the locus is epigenetically silenced, and all
      resulting Arf (+/+) tumors failed to express the p19(Arf) protein. In striking
      contrast, retention of Arf in thymocyte-derived ICN1+ donor cells significantly
      delayed disease onset and suppressed the penetrance of T-ALL. Use of cultured
      thymocyte-derived donor cells expressing a functionally null Arf-GFP knock-in
      allele confirmed that ICN1 signaling can induce Arf expression in vivo. Arf
      activation by ICN1 in T cells thereby provides stage-specific tumor suppression
      but also a strong selective pressure for deletion of the locus in T-ALL.

PMID- 19759356
TI  - Generation of Epstein-Barr virus-specific cytotoxic T lymphocytes resistant to
      the immunosuppressive drug tacrolimus (FK506).
AB  - Adoptive transfer of autologous Epstein-Barr virus-specific cytotoxic T
      lymphocytes (EBV-CTLs) to solid organ transplant (SOT) recipients has been shown
      safe and effective for the treatment of EBV-associated posttransplantation
      lymphoproliferative disorders (PTLDs). SOT recipients, however, require the
      continuous administration of immunosuppressive drugs to prevent graft rejection,
      and these agents may significantly limit the long-term persistence of transferred
      EBV-CTLs, precluding their use as prophylaxis. Tacrolimus (FK506) is one of the
      most widely used immunosuppressive agents in SOT recipients, and its
      immunosuppressive effects are largely dependent on its interaction with the 12
      kDa FK506-binding protein (FKBP12). We have knocked down the expression of FKBP12
      in EBV-CTLs using a specific small interfering RNA (siRNA) stably expressed from
      a retroviral vector and found that FKBP12-silenced EBV-CTLs are FK506 resistant.
      These cells continue to expand in the presence of the drug without measurable
      impairment of their antigen specificity or cytotoxic activity. We confirmed their
      FK506 resistance and anti-PTLD activity in vivo using a xenogenic mouse model,
      suggesting that the proposed strategy may be of value to enhance EBV-specific
      immune surveillance in patients at high risk of PTLD after transplantation.

PMID- 19759357
TI  - BMP4 regulates the hematopoietic stem cell niche.
AB  - Bone morphogenetic protein 4 (BMP4) is required for mesoderm commitment to the
      hematopoietic lineage during early embryogenesis. However, deletion of BMP4 is
      early embryonically lethal and its functional role in definitive hematopoiesis is
      unknown. Consequently, we used a BMP4 hypomorph to investigate the role of BMP4
      in regulating hematopoietic stem cell (HSC) function and maintaining steady-state
      hematopoiesis in the adult. Reporter gene expression shows that Bmp4 is expressed
      in cells associated with the hematopoietic microenvironment including
      osteoblasts, endothelial cells, and megakaryocytes. Although resting
      hematopoiesis is normal in a BMP4-deficient background, the number of c-Kit+, Sca
      1+, Lineage- cells is significantly reduced. Serial transplantation studies
      reveal that BMP4-deficient recipients have a microenvironmental defect that
      reduces the repopulating activity of wild-type HSCs. This defect is even more
      pronounced in a parabiosis model that demonstrates a profound reduction in wild
      type hematopoietic cells within the bone marrow of BMP4-deficient recipients.
      Furthermore, wild-type HSCs that successfully engraft into the BMP4-deficient
      bone marrow show a marked decrease in functional stem cell activity when tested
      in a competitive repopulation assay. Taken together, these findings indicate BMP4
      is a critical component of the hematopoietic microenvironment that regulates both
      HSC number and function.

PMID- 19759358
TI  - Defects in osteoblast function but no changes in long-term repopulating potential
      of hematopoietic stem cells in a mouse chronic inflammatory arthritis model.
AB  - Recent studies support the notion that there is an intricate relationship between
      hematopoiesis and bone homeostasis in normal steady states. Using mice undergoing
      chronic inflammatory arthritis, we investigated the relationship between
      hematopoiesis and bone homeostasis in pathologic conditions. We demonstrate that
      mice undergoing chronic inflammatory arthritis displayed osteoporosis resulting
      from a severe defect in osteoblast function. Despite the defective osteoblast
      function, however, the hematopoietic stem cells from these mice exhibited normal
      properties in either long-term repopulation or cell cycling. Therefore, the bone
      forming capacity of osteoblasts is distinct from their ability to maintain
      hematopoietic stem cells in chronic inflammatory conditions.

PMID- 19759361
TI  - High test-retest reliability of the extended version of the "Sniffin' Sticks"
      test.
AB  - The "Sniffin' Sticks" test kit is a validated and commonly used tool for
      assessment of olfactory function in subjects with normal sense of smell and in
      individuals with smell loss. That test incorporates subtests for odor threshold,
      discrimination, and identification. To gain higher subtest reproducibility, tests
      on odor discrimination and odor identification were extended using 32 instead of
      the usually applied 16 single trials each. In developing the extended Sniffin'
      Sticks test, a number of preliminary experiments were performed in 46 healthy,
      normosmic individuals 1) to evaluate intensity and familiarity of the
      additionally selected odors, 2) to select distractors for the discrimination and
      identification test, and 3) to evaluate the test-retest reliability of each
      subtest. Furthermore, the extended test was applied to 126 patients with
      olfactory loss and 71 normosmic individuals. Follow-up investigation could be
      performed in 69 controls within an average interval of 4 days. Results revealed
      significant differences between patients and healthy subjects. Estimated
      intensity and familiarity of the newly selected 16 items of the discrimination
      test did not differ significantly from the 16 standard items. Test-retest
      reliability was found to be r = 0.80 (odor discrimination), r = 0.88 (odor
      identification), and r = 0.92 (odor threshold). In conclusion, the extended test
      kit allows a precise evaluation of olfactory function, especially when different
      olfactory tasks are assessed using individual subtests. Furthermore, the high
      test-retest reliability of both the 16 and the 32-item tests allows the
      evaluation of even relatively small changes of olfactory function over time by
      means of either test.

PMID- 19759360
TI  - Expression patterns of odorant receptors and response properties of olfactory
      sensory neurons in aged mice.
AB  - The sense of smell deteriorates in normal aging, but the underling mechanisms are
      still elusive. Here we investigated age-related alterations in expression
      patterns of odorant receptor (OR) genes and functional properties of olfactory
      sensory neurons (OSNs)-2 critical factors that define the odor detection
      threshold in the olfactory epithelium. Using in situ hybridization for 9
      representative OR genes, we compared the cell densities of each OR in coronal
      nose sections at different ages (3-27 months). The cell density for different ORs
      peaked at different time points and a decline was observed for 6 of 9 ORs at
      advanced ages. Using patch clamp recordings, we then examined the odorant
      responses of individual OSNs coexpressing a defined OR (MOR23) and green
      fluorescent protein. The MOR23 neurons recorded from aged animals maintained a
      similar sensitivity and dynamic range in response to the cognate odorant (lyral)
      as those from younger mice. The results indicate that although the cell densities
      of OSNs expressing certain types of ORs decline at advanced ages, individual OSNs
      can retain their sensitivity. The implications of these findings in age-related
      olfactory deterioration are discussed.

PMID- 19759362
TI  - Profiles of volatiles in male rat urine: the effect of puberty on the female
      attraction.
AB  - Rat urine contains many volatile constituents that may be used for chemical
      communication. The levels of certain urinary volatiles are strongly dependent on
      the sex and endocrine status (e.g., puberty). We performed chemical and
      behavioral studies to identify the volatiles in adult male rat urine that attract
      mature females. Our results demonstrated that adult male rats have higher levels
      of 2-heptanone (2-HP), 4-methylphenol (4-MP), and 4-ethylphenol (4-EP) than
      prepubescent male rats; furthermore, female rats are more attracted to the odor
      of adult male rat urine than that of prepubescent males. When prepubescent rat
      urine was supplemented with 2-HP, 4-MP, and 4-EP to the levels found in adult
      male urine, the attractiveness of the urine to females was markedly enhanced. Our
      results suggested that this attraction is due to an increased level of
      chemosignaling.

PMID- 19759363
TI  - Chemical polymorphism and chemosensory recognition between Iberolacerta monticola
      lizard color morphs.
AB  - In the lizard Iberolacerta monticola, there are 2 discrete color morphs ("blue"
      vs. "green") that seem to have alternative reproductive strategies. Because scent
      marking of territories and chemoreception are important in social organization of
      these lizards, we explored whether there is also chemical polymorphism and
      chemosensory recognition between color morphs. Analyses by gas chromatography
      mass spectrometry showed that adult males of different morphs had similar
      chemical compounds in femoral gland secretions, but the proportions of some
      shared chemicals were different; blue morph males had higher proportions of
      steroids and lower proportions of fatty acids than green males. Differential
      tongue-flick rates to scents from femoral secretions of males indicated that
      males were able to detect the scent of any male from a baseline odorless control
      (water) but did not discriminate between the scent of males of different morphs.
      In contrast, females detected and discriminated between scents of the 2 male
      morphs by chemical cues alone. We suggest that differences in males' chemical
      signals between morphs and the ability of females of discriminating chemically
      between male morphs might be required to maintain spatial behavior, social
      organization, and mate choice decisions and, thus, be important for the
      maintenance of alternative reproductive strategies and polymorphism in lizards.

PMID- 19759364
TI  - Decreased incidence of hepatocellular carcinoma in hepatitis B vaccinees: a 20
      year follow-up study.
AB  - BACKGROUND: Hepatitis B virus (HBV) infection is a major cause of hepatocellular
      carcinoma. This population-based study aimed to investigate whether prevention of
      hepatocellular carcinoma by the universal Taiwanese HBV vaccine program, launched
      in July 1984, has extended beyond childhood and to identify the predictors of
      hepatocellular carcinoma for vaccinated birth cohorts. METHODS: Data on 1958
      patients with hepatocellular carcinoma who were aged 6-29 years at diagnosis in
      Taiwan between 1983 and 2004 were collected from two national hepatocellular
      carcinoma registries. Age- and sex-specific incidence among vaccinated and
      unvaccinated birth cohorts were analyzed by using Poisson regression models. All
      statistical tests were two-sided. Records of 64 hepatocellular carcinoma patients
      and 5 524 435 HBV vaccinees who were born after the initiation of the vaccination
      program were compared for HBV immunization characteristics during infancy and
      prenatal maternal hepatitis B surface antigen (HBsAg) and e antigen (HBeAg)
      serostatus. RESULTS: Hepatocellular carcinoma incidence was statistically
      significantly lower among children aged 6-19 years in vaccinated compared with
      unvaccinated birth cohorts (64 hepatocellular cancers among vaccinees in 37 709
      304 person-years vs 444 cancers in unvaccinated subjects in 78 496 406 person
      years, showing an age- and sex-adjusted relative risk of 0.31, P < .001, for
      persons vaccinated at birth). The risk of developing hepatocellular carcinoma for
      vaccinated cohorts was statistically significantly associated with incomplete HBV
      vaccination (for those who received fewer than three doses of HBV vaccine, odds
      ratio [OR] = 4.32, 95% confidence interval [CI] = 2.34 to 7.91); with prenatal
      maternal HBsAg seropositivity (OR = 29.50, 95% CI = 13.98 to 62.60); with
      prenatal maternal HBeAg seropositivity (with administration of hepatitis B
      immunoglobulin at birth, OR = 5.13, 95% CI = 2.24 to 11.71; and without it, OR =
      9.43, 95% CI = 3.54 to 25.11). CONCLUSION: The prevention of hepatocellular
      carcinoma by this HBV vaccine extends from childhood to early adulthood. Failure
      to prevent hepatocellular carcinoma results mostly from unsuccessful control of
      HBV infection by highly infectious mothers.

PMID- 19759365
TI  - Rapid appearance of new cerebral microbleeds after acute ischemic stroke.
AB  - BACKGROUND: It is unknown whether the development of cerebral microbleeds (MBs),
      small areas of signal loss on T2*-weighted gradient-echo imaging (GRE), follows a
      slow or a rapid process. We hypothesized that MBs may develop rapidly after
      certain critical events, such as strokes, and investigated the frequency,
      location, and factors associated with the formation of new MBs after acute
      ischemic stroke. METHODS: We retrospectively examined 237 consecutive acute
      ischemic stroke patients who underwent MRI within 24 hours and follow-up MRI
      during the week after symptom onset. We defined new MBs as MBs that newly
      appeared on follow-up GRE outside the infarcted area. We examined the association
      of new MBs with demographics, risk factors, laboratory data, baseline MBs, and
      small vessel disease (SVD; leukoaraiosis and lacunar infarctions). RESULTS:
      Seventy-five patients (31.6%) had baseline MBs, and 30 (12.7%) developed new MBs.
      Multiple logistic regression analysis indicated that the presence of baseline MBs
      (odds ratio [OR] 5.72, 95% confidence interval [CI] 2.12-15.42, p = 0.001) and
      severe SVD (OR 2.94, 95% CI 1.12-7.77, p = 0.03) independently predicted the
      development of new MBs. Of the 56 new MBs, 29 (51.8%) appeared in the lobar
      location, 17 (30.4%) appeared in the deep location, and 10 (17.9%) appeared in
      the infratentorial location. CONCLUSIONS: This study suggests that new
      microbleeds (MBs) can develop rapidly after acute ischemic stroke. Baseline MBs
      and severe small vessel disease are predictors for the development of new MBs.
      Further studies will be needed to investigate the clinical implications and
      mechanisms of these findings.

PMID- 19759366
TI  - Phosphoglycerate kinase 2 (PGK2) is essential for sperm function and male
      fertility in mice.
AB  - Phosphoglycerate kinase 2 (PGK2), an isozyme that catalyzes the first ATP
      generating step in the glycolytic pathway, is encoded by an autosomal retrogene
      that is expressed only during spermatogenesis. It replaces the ubiquitously
      expressed phosphoglycerate kinase 1 (PGK1) isozyme following repression of Pgk1
      transcription by meiotic sex chromosome inactivation during meiotic prophase and
      by postmeiotic sex chromatin during spermiogenesis. The targeted disruption of
      Pgk2 by homologous recombination eliminates PGK activity in sperm and severely
      impairs male fertility, but does not block spermatogenesis. Mating behavior,
      reproductive organ weights (testis, excurrent ducts, and seminal vesicles),
      testis histology, sperm counts, and sperm ultrastructure were indistinguishable
      between Pgk2(-/-) and wild-type mice. However, sperm motility and ATP levels were
      markedly reduced in males lacking PGK2. These defects in sperm function were
      slightly less severe than observed in males lacking glyceraldehyde-3-phosphate
      dehydrogenase, spermatogenic (GAPDHS), the isozyme that catalyzes the step
      preceding PGK2 in the sperm glycolytic pathway. Unlike Gapdhs(-/-) males, the
      Pgk2(-/-) males also sired occasional pups. Alternative pathways that bypass the
      PGK step of glycolysis exist. We determined that one of these bypass enzymes,
      acylphosphatase, is active in mouse sperm, perhaps contributing to phenotypic
      differences between mice lacking GAPDHS or PGK2. This study determined that PGK2
      is not required for the completion of spermatogenesis, but is essential for sperm
      motility and male fertility. In addition to confirming the importance of the
      glycolytic pathway for sperm function, distinctive phenotypic characteristics of
      Pgk2(-/-) mice may provide further insights into the regulation of sperm
      metabolism.

PMID- 19759367
TI  - Proteasomal activity is required to initiate and to sustain translational
      activation of messenger RNA encoding the stem-loop-binding protein during meiotic
      maturation in mice.
AB  - Developmentally regulated translation plays a key role in controlling gene
      expression during oogenesis. In particular, numerous mRNA species are
      translationally repressed in growing oocytes and become translationally activated
      during meiotic maturation. While many studies have focused on a U-rich sequence,
      termed the cytoplasmic polyadenylation element (CPE), located in the 3'
      untranslated region (UTR) and the CPE-binding protein (CPEB) 1, multiple
      mechanisms likely contribute to translational control in oocytes. The stem-loop
      binding protein (SLBP) is expressed in growing oocytes, where it is required for
      the accumulation of nonpolyadenylated histone mRNAs, and then accumulates
      substantially during meiotic maturation. We report that, in immature oocytes,
      Slbp mRNA carries a short poly(A) tail, and is weakly translated, and that a CPE
      like sequence in the 3'-UTR is required to maintain this low activity. During
      maturation, Slbp mRNA becomes polyadenylated and translationally activated.
      Unexpectedly, proteasomal activity is required both to initiate and to sustain
      translational activation. This proteasomal activity is not required for the
      polyadenylation of Slbp mRNA during early maturation; however, it is required for
      a subsequent deadenylation of the mRNA that occurs during late maturation.
      Moreover, although CPEB1 is degraded during maturation, inhibiting its
      degradation by blocking mitogen-activated protein kinase 1/3 activity does not
      prevent the accumulation of SLBP, indicating that CPEB1 is not the protein whose
      degradation is required for translational activation of Slbp mRNA. These results
      identify a new role for proteasomal activity in initiating and sustaining
      translational activation during meiotic maturation.

PMID- 19759368
TI  - Influences of sex, incubation temperature, and environmental quality on gonadal
      estrogen and androgen receptor messenger RNA expression in juvenile American
      alligators (Alligator mississippiensis).
AB  - Gonadal steroid hormone receptors play a vital role in transforming ligand
      signals into gene expression. We have shown previously that gonads from wild
      caught juvenile alligators express greater levels of estrogen receptor 1 (ESR1)
      than estrogen receptor 2 (ESR2). Furthermore, sexually dimorphic ESR2 mRNA
      expression (female > male) observed in animals from the reference site (Lake
      Woodruff, FL, USA) was lost in alligators from the contaminated Lake Apopka (FL,
      USA). We postulated that environmental contaminant exposure could influence
      gonadal steroid hormone receptor expression. Here, we address questions regarding
      gonadal estrogen and androgen receptor (AR) mRNA expression in 1-yr-old,
      laboratory-raised alligators. What are relative expression levels within gonads?
      Do these levels vary between sexes or incubation temperatures? Can contaminant
      exposure change these levels? We observed a similar pattern of expression (ESR1 >
      AR > ESR2) in ovary and testis. However, both incubation temperature and
      environment modulated expression. Males incubated at 33.5 degrees C expressed
      greater AR levels than females incubated at 30 degrees C; dimorphic expression
      was not observed in animals incubated at 32 degrees C. Compared to Lake Woodruff
      alligators, Lake Apopka animals of both sexes showed lesser ESR2 mRNA expression
      levels. Employing cluster analyses, we integrated these receptor expression
      patterns with those of steroidogenic factors. Elevated ESR2 and CYP19A1
      expressions were diagnostic of alligator ovary, whereas elevated HSD3B1, CYP11A1,
      and CYP17A1 expressions were indicative of testis. In contrast, AR, ESR1, and
      NR5A1 showed variable expressions that were not entirely associated with sex.
      These findings demonstrate that the mRNA expression of receptors required for
      steroid hormone signaling are modified by exposure to environmental factors,
      including temperature and contaminants.

PMID- 19759370
TI  - Genetic susceptibility to restenosis: role of bone marrow cells and inflammatory
      response.

PMID- 19759371
TI  - Factor XI binding to platelets: glycoprotein Ib alpha has an accomplice.

PMID- 19759372
TI  - ATVB in focus. Monocyte subsets and their relevance to cardiovascular diseases.
      Editorial.

PMID- 19759373
TI  - Regulation of the migration and survival of monocyte subsets by chemokine
      receptors and its relevance to atherosclerosis.
AB  - Monocytes are central mediators in the advance of atherosclerotic plaque, making
      them a natural therapeutic target for reducing disease burden. Here, we highlight
      recent advances in our current understanding of monocyte heterogeneity and its
      relevance to regulation of monocyte accumulation and function within
      atherosclerotic plaques. Differences that distinguish monocyte subsets include
      differential expression of chemokine receptors, especially CCR2 and CX3CR1.
      Ablation of expression of these 2 receptors (or their ligands) in mice has an
      additive inhibition on monocyte recruitment to atherosclerotic plaques. Moreover,
      simultaneously interfering with 3 key pathways--CCR2, CX3CR1, and CCR5-
      essentially abolishes atherosclerosis in mice. Here, we discuss how these
      chemokine receptors act at multiple points on at least 1 monocyte subset,
      regulating their mobilization from bone marrow, survival, or recruitment to
      plaques. Finally, we discuss how this knowledge may be useful clinically,
      emphasizing that CX3CR1 may in particular be a viable target for therapeutic
      manipulation of monocyte-derived cell fate in cardiovascular disease.

PMID- 19759374
TI  - Estrogen decreases atherosclerosis in part by reducing hepatic acyl
      CoA:cholesterol acyltransferase 2 (ACAT2) in monkeys.
AB  - OBJECTIVE: Estrogens decrease atherosclerosis progression, mediated in part
      through changes in plasma lipids and lipoproteins. This study aimed to determine
      estrogen-induced changes in hepatic cholesterol metabolism, plasma lipoproteins,
      and the relationship of these changes to atherosclerosis extent. METHODS AND
      RESULTS: Ovariectomized monkeys (n=34) consumed atherogenic diets for 30 months
      which contained either no hormones (control, n=17) or conjugated equine estrogens
      (CEE, n=17) at a human dose equivalent of 0.625 mg/d. Hepatic cholesterol
      content, low-density lipoprotein (LDL) receptor expression, cholesterol 7 alpha
      hydroxylase and acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity, and
      expression levels were determined. CEE treatment resulted in lower plasma
      concentrations of very-low- and intermediate- density lipoprotein cholesterol
      (V+IDLC; P=0.01), smaller LDL particles (P=0.002), and 50% lower hepatic
      cholesterol content (total, free, and esterified; P<0.05 for all). Total ACAT
      activity was significantly lower (P=0.01), explained primarily by reductions in
      the activity of ACAT2. Estrogen regulation of enzymatic activity was at the
      protein level as both ACAT1 and 2 protein, but not mRNA levels, were lower
      (P=0.02 and <0.0001, respectively). ACAT2 activity was significantly associated
      with hepatic total cholesterol, plasma V+IDLC cholesterol, and atherosclerosis.
      CONCLUSIONS: Atheroprotective effects of estrogen therapy may be related to
      reduced hepatic secretion of ACAT2-derived cholesteryl esters in plasma
      lipoproteins.

PMID- 19759375
TI  - PYK2/PDZ-RhoGEF links Ca2+ signaling to RhoA.
AB  - OBJECTIVE: Ras homolog gene family member A (RhoA)/Rho-kinase-mediated Ca(2+)
      sensitization is a critical component of constrictor responses. The present study
      investigates how angiotensin II activates RhoA. METHODS AND RESULTS: Adenoviral
      vectors were used to manipulate the expression of regulator of G protein
      signaling (RGS) domain containing Rho-specific guanine exchange factors (RhoGEFs)
      and proline-rich tyrosine kinase 2 (PYK2), a nonreceptor tyrosine kinase, in
      primary rat vascular smooth muscle cells. As an evidence of RhoA activation, RhoA
      translocation and MYPT1 (the regulatory subunit of myosin light chain
      phosphatase) phosphorylation were analyzed by Western blot. Results showed that
      overexpression of PDZ-RhoGEF, but not p115-RhoGEF or leukemia-associated RhoGEF
      (LARG), enhanced RhoA activation by angiotensin II. Knockdown of PDZ-RhoGEF
      decreased RhoA activation by angiotensin II. PDZ-RhoGEF was phosphorylated and
      activated by PYK2 in vitro, and knockdown of PDZ-RhoGEF reduced RhoA activation
      by constitutively active PYK2, indicating that PDZ-RhoGEF links PYK2 to RhoA.
      Knockdown of PYK2 or PDZ-RhoGEF markedly decreased RhoA activation by A23187, a
      Ca(2+) ionophore, demonstrating that PYK2/PDZ-RhoGEF couples RhoA activation to
      Ca(2+). CONCLUSIONS: PYK2 and PDZ-RhoGEF are necessary for angiotensin II-induced
      RhoA activation and for Ca(2+) signaling to RhoA.

PMID- 19759376
TI  - Differential associations between soluble cellular adhesion molecules and
      atherosclerosis in the Dallas Heart Study: a distinct role for soluble
      endothelial cell-selective adhesion molecule.
AB  - OBJECTIVE: Endothelial cell-selective adhesion molecule (ESAM) is a junctional
      type cellular adhesion molecule (CAM) that is uniquely expressed in vascular
      endothelium and activated platelets and mediates neutrophil and monocyte
      diapedesis across the endothelium. Given its role in endothelial pathobiology, we
      hypothesized that soluble ESAM (sESAM) would be independently associated with
      atherosclerosis and vascular stiffness. METHODS AND RESULTS: We measured sESAM,
      soluble intercellular adhesion molecule (sICAM)-1, and soluble vascular cell
      adhesion molecule (sVCAM)-1 in 3222 subjects participating in the Dallas Heart
      Study, a probability-based population sample. Coronary artery calcium (CAC) was
      measured by electron beam computed tomography, and abdominal aortic wall
      thickness (AWT), aortic plaque burden (APB), and aortic compliance (AC) by MRI.
      Increasing levels of sESAM were associated with all major cardiovascular risk
      factors as well as with inflammatory markers such as monocyte chemoattractant
      protein-1, but only weakly correlated with sICAM-1 and sVCAM-1. In multivariate
      analyses, sESAM was independently associated with prevalent CAC (OR 1.2 per SD
      increase, 95% CI 1.1 to 1.3; P=0.005), AWT (P=0.035), and AC (P=0.006), but not
      APB (P=0.15). In contrast, no independent associations were observed between
      sICAM-1 or sVCAM-1 and any of the atherosclerosis phenotypes. CONCLUSIONS: In
      this first reported clinical study of sESAM in humans, sESAM levels were
      independently associated with CAC, AWT, and AC, whereas sICAM-1 and sVCAM-1 were
      not. These findings support a unique role of this cellular adhesion molecule in
      atherosclerosis and suggest the need for further exploration of sESAM as a
      predictive biomarker and potential mediator of atherosclerosis.

PMID- 19759378
TI  - Opportunities and challenges for the NIH--an interview with Francis Collins.
      Interview by Robert Steinbrook.

PMID- 19759377
TI  - The public health and economic benefits of taxing sugar-sweetened beverages.

PMID- 19759379
TI  - Images in clinical medicine. Uvular necrosis after endoscopy.

PMID- 19759380
TI  - Clinical practice. Screening for colorectal cancer.

PMID- 19759381
TI  - Images in clinical medicine. Acquired melanonychia.

PMID- 19759382
TI  - Case records of the Massachusetts General Hospital. Case 29-2009. An 81-year-old
      man with weight loss, odynophagia, and failure to thrive.

PMID- 19759383
TI  - Good law from tragic facts--Congress, the FDA, and preemption.

PMID- 19759384
TI  - Duration of androgen suppression in prostate cancer.

PMID- 19759385
TI  - Fomepizole for toxic alcohol poisoning.

PMID- 19759386
TI  - More on B-cell-depleting induction therapy and acute cellular rejection.

PMID- 19759387
TI  - A classic twin study of external ear malformations, including microtia.

PMID- 19759388
TI  - Luteinizing hormone-releasing hormone and postmenopausal flushing.

PMID- 19759389
TI  - Preparation of fatty acid methyl esters for gas-liquid chromatography.
AB  - A convenient method using commercial aqueous concentrated HCl (conc. HCl; 35%,
      w/w) as an acid catalyst was developed for preparation of fatty acid methyl
      esters (FAMEs) from sterol esters, triacylglycerols, phospholipids, and FFAs for
      gas-liquid chromatography (GC). An 8% (w/v) solution of HCl in methanol/water
      (85:15, v/v) was prepared by diluting 9.7 ml of conc. HCl with 41.5 ml of
      methanol. Toluene (0.2 ml), methanol (1.5 ml), and the 8% HCl solution (0.3 ml)
      were added sequentially to the lipid sample. The final HCl concentration was 1.2%
      (w/v). This solution (2 ml) was incubated at 45 degrees C overnight or heated at
      100 degrees C for 1-1.5 h. The amount of FFA formed in the presence of water
      derived from conc. HCl was estimated to be <1.4%. The yields of FAMEs were >96%
      for the above lipid classes and were the same as or better than those obtained by
      saponification/methylation or by acid-catalyzed methanolysis/methylation using
      commercial anhydrous HCl/methanol. The method developed here could be
      successfully applied to fatty acid analysis of various lipid samples, including
      fish oils, vegetable oils, and blood lipids by GC.

PMID- 19759390
TI  - Safety evaluation of calcium administered intranasally to mice.
AB  - Calcium, a component of approved human vaccines administered via systemic routes,
      has a good safety profile. Recently, intranasally administered vaccines
      containing calcium have shown promise in generating mucosal immune responses in
      animal models. However, the safety of intranasally administered calcium is
      unknown. This study evaluates the safety of intranasally administered calcium at
      2- to 13-fold higher doses than used in experimental vaccines. At a calcium dose
      of 22 mg/kg, 80% of the Balb/c and 20% of the C57BL/6 mice die within the first
      24 hours. At 11.0 mg/kg, there is no overt toxicity in either strain, based on
      body weight, clinical scores, blood chemistry, and histopathology of major organs
      at 7 days post administration. In C57BL/6 mice, apart from acute and subacute
      inflammation in the lungs at up to 3 days post administration, especially at the
      22-mg/kg dose, there is no overt toxicity. Doses of calcium up to 11 mg/kg appear
      to be safe in a mouse model.

PMID- 19759391
TI  - Safety and risk management interventions in hospitals: a systematic review of the
      literature.
AB  - The aim of this systematic review was (a) to synthesize the evidence on the
      effectiveness of detection, mitigation, and actions to reduce risks in hospitals
      and (b) to identify and describe components of interventions responsible for
      effectiveness. Thirteen literature databases were explored using a structured
      search and data extraction strategy. All included studies dealing with incident
      reporting described positive effects. Evidence regarding the effectiveness and
      efficiency of safety analysis is scarce. No studies on mitigation were included.
      The collected evidence on risk reduction concerns a variety of interventions to
      reduce medication errors, fall incidents, diagnostic errors, and adverse events
      in general. Most studies reported positive effects; however, interventions were
      often multifaceted, and it was difficult to disentangle their impact. This made
      it difficult to draw generic lessons from this body of research. More rigorous
      evaluations are needed, in particular, of continuous learning and safety analysis
      techniques.

PMID- 19759393
TI  - Kinesin-1 regulates microtubule dynamics via a c-Jun N-terminal kinase-dependent
      mechanism.
AB  - In the kinesin family, all the molecular motors that have been implicated in the
      regulation of microtubule dynamics have been shown to stimulate microtubule
      depolymerization. Here, we report that kinesin-1 (also known as conventional
      kinesin or KIF5B) stimulates microtubule elongation and rescues. We show that
      microtubule-associated kinesin-1 carries the c-Jun N-terminal kinase (JNK) to
      allow its activation and that microtubule elongation requires JNK activity
      throughout the microtubule life cycle. We also show that kinesin-1 and JNK
      promoted microtubule rescues to similar extents. Stimulation of microtubule
      rescues by the kinesin-1/JNK pathway could not be accounted for by the rescue
      factor CLIP-170. Indeed only a dual inhibition of kinesin-1/JNK and CLIP-170
      completely blocked rescues and led to extensive microtubule loss. We propose that
      the kinesin-1/JNK signaling pathway is a major regulator of microtubule dynamics
      in living cells and that it is required with the rescue factor CLIP-170 to allow
      cells to build their interphase microtubule network.

PMID- 19759394
TI  - The ATPase cycle of the mitotic motor CENP-E.
AB  - We have previously shown that the mitotic motor centrosome protein E (CENP-E) is
      capable of walking for more than 250 steps on its microtubule track without
      dissociating. We have examined the kinetics of this molecular motor to see if its
      enzymology explains this remarkable degree of processivity. We find that like the
      highly processive transport motor kinesin 1, the enzymatic cycle of CENP-E is
      characterized by rapid ATP binding, multiple enzymatic turnovers per diffusive
      encounter, and gating of nucleotide binding. These features endow CENP-E with a
      high duty cycle, a prerequisite for processivity. However, unlike kinesin 1, neck
      linker docking in CENP-E is slow, occurring at a rate closer to that for Eg5, a
      mitotic kinesin that takes only 5-10 steps per processive run. These results
      suggest that like kinesin 1, features outside of the catalytic domain of CENP-E
      may also play a role in regulating the processive behavior of this motor.

PMID- 19759395
TI  - N terminus of CtIP is critical for homologous recombination-mediated double
      strand break repair.
AB  - DNA double-strand breaks (DSBs) represent one of the most lethal types of DNA
      damage cells encounter. CtIP (also known as RBBP8) acts together with the MRN
      (MRE11-RAD50-NBS1) complex to promote DNA end resection and the generation of
      single-stranded DNA, which is critically important for homologous recombination
      repair. However, it is not yet clear exactly how CtIP participates in this
      process. Here, we demonstrate that besides the known conserved C terminus, the N
      terminus of CtIP protein is also required in DSB end resection and DNA damage
      induced G(2)/M checkpoint control. We further show that both termini of CtIP can
      interact with the MRN complex and that the N terminus of CtIP, especially
      residues 22-45, binds to MRN and plays a critical role in targeting CtIP to sites
      of DNA breaks. Collectively, our results highlight the importance of the N
      terminus of CtIP in directing its localization and function in DSB repair.

PMID- 19759396
TI  - Interactions of plakoglobin and beta-catenin with desmosomal cadherins: basis of
      selective exclusion of alpha- and beta-catenin from desmosomes.
AB  - Plakoglobin and beta-catenin are homologous armadillo repeat proteins found in
      adherens junctions, where they interact with the cytoplasmic domain of classical
      cadherins and with alpha-catenin. Plakoglobin, but normally not beta-catenin, is
      also a structural constituent of desmosomes, where it binds to the cytoplasmic
      domains of the desmosomal cadherins, desmogleins and desmocollins. Here, we
      report structural, biophysical, and biochemical studies aimed at understanding
      the molecular basis of selective exclusion of beta-catenin and alpha-catenin from
      desmosomes. The crystal structure of the plakoglobin armadillo domain bound to
      phosphorylated E-cadherin shows virtually identical interactions to those
      observed between beta-catenin and E-cadherin. Trypsin sensitivity experiments
      indicate that the plakoglobin arm domain by itself is more flexible than that of
      beta-catenin. Binding of plakoglobin and beta-catenin to the intracellular
      regions of E-cadherin, desmoglein1, and desmocollin1 was measured by isothermal
      titration calorimetry. Plakoglobin and beta-catenin bind strongly and with
      similar thermodynamic parameters to E-cadherin. In contrast, beta-catenin binds
      to desmoglein-1 more weakly than does plakoglobin. beta-Catenin and plakoglobin
      bind with similar weak affinities to desmocollin-1. Full affinity binding of
      desmoglein-1 requires sequences C-terminal to the region homologous to the
      catenin-binding domain of classical cadherins. Although pulldown assays suggest
      that the presence of N- and C-terminal beta-catenin "tails" that flank the
      armadillo repeat region reduces the affinity for desmosomal cadherins,
      calorimetric measurements show no significant effects of the tails on binding to
      the cadherins. Using purified proteins, we show that desmosomal cadherins and
      alpha-catenin compete directly for binding to plakoglobin, consistent with the
      absence of alpha-catenin in desmosomes.

PMID- 19759397
TI  - Multivalency in the assembly of intrinsically disordered Dynein intermediate
      chain.
AB  - Dynein light chains are thought to increase binding efficiency of dynein
      intermediate chain to both dynein heavy chain and dynactin, but their exact role
      is not clear. Isothermal titration calorimetry and x-ray crystallography reported
      herein indicate that multivalency effects underlie efficient dynein assembly and
      regulation. For a ternary complex of a 60-amino acid segment of dynein
      intermediate chain (IC) bound to two homodimeric dynein light chains Tctex1 and
      LC8, there is a 50-fold affinity enhancement for the second light chain binding.
      For a designed IC construct containing two LC8 sites, observed the 1000-fold
      enhancement reflects a remarkably pure entropic chelate effect of a magnitude
      commensurate with theoretical predictions. The lower enhancement in wild-type IC
      is attributed to unfavorable free energy changes associated with incremental
      interactions of IC with Tctex1. Our results show assembled dynein IC as an
      elongated, flexible polybivalent duplex, and suggest that polybivalency is an
      important general mechanism for constructing stable yet reversible and
      functionally versatile complexes.

PMID- 19759398
TI  - Dynamic interaction of amphiphysin with N-WASP regulates actin assembly.
AB  - Amphiphysin 1, an endocytic adaptor concentrated at synapses that couples
      clathrin-mediated endocytosis to dynamin-dependent fission, was also shown to
      have a regulatory role in actin dynamics. Here, we report that amphiphysin 1
      interacts with N-WASP and stimulates N-WASP- and Arp2/3-dependent actin
      polymerization. Both the Src homology 3 and the N-BAR domains are required for
      this stimulation. Acidic liposome-triggered, N-WASP-dependent actin
      polymerization is strongly impaired in brain cytosol of amphiphysin 1 knock-out
      mice. FRET-FLIM analysis of Sertoli cells, where endogenously expressed
      amphiphysin 1 co-localizes with N-WASP in peripheral ruffles, confirmed the
      association between the two proteins in vivo. This association undergoes
      regulation and is enhanced by stimulating phosphatidylserine receptors on the
      cell surface with phosphatidylserine-containing liposomes that trigger ruffle
      formation. These results indicate that actin regulation is a key function of
      amphiphysin 1 and that such function cooperates with the endocytic adaptor role
      and membrane shaping/curvature sensing properties of the protein during the
      endocytic reaction.

PMID- 19759399
TI  - GM3 synthase overexpression results in reduced cell motility and in caveolin-1
      upregulation in human ovarian carcinoma cells.
AB  - In this paper, we describe the effects of the expression of GM3 synthase at high
      levels in human ovarian carcinoma cells. Overexpression of GM3 synthase in A2780
      cells consistently resulted in elevated ganglioside (GM3, GM2 and GD1a) levels.
      GM3 synthase overexpressing cells had a growth rate similar to wild-type cells,
      but showed a strongly reduced in vitro cell motility accompanied by reduced
      levels of the epithelial-mesenchymal transition marker alpha smooth muscle actin.
      A similar reduction in cell motility was observed upon treatment with exogenous
      GM3, GM2, and GM1, but not with GD1a. A photolabeling experiment using
      radioactive and photoactivable GM3 highlighted several proteins directly
      interacting with GM3. Among those, caveolin-1 was identified as a GM3-interacting
      protein in GM3 synthase overexpressing cells. Remarkably, caveolin-1 was markedly
      upregulated in GM3 synthase overexpressing cells. In addition, the motility of
      low GM3 synthase expressing cells was also reduced in the presence of a Src
      kinase inhibitor; on the other hand, higher levels of the inactive form of c-Src
      were detected in GM3 synthase overexpressing cells, associated with a ganglioside
      and caveolin-rich detergent insoluble fraction.

PMID- 19759400
TI  - Insulin enhances the biogenesis of nuclear sterol regulatory element-binding
      protein (SREBP)-1c by posttranscriptional down-regulation of Insig-2A and its
      dissociation from SREBP cleavage-activating protein (SCAP).SREBP-1c complex.
AB  - The regulation of lipid homeostasis by insulin is mediated in part by the
      enhanced transcription of the gene encoding sterol regulatory element-binding
      protein-1c (SREBP-1c). The nascent SREBP-1c is embedded in the endoplasmic
      reticulum (ER) and must be transported to the Golgi where two sequential
      cleavages generate its NH(2)-terminal fragment, nSREBP-1c. We have shown recently
      that in primary cultures of rat hepatocytes, insulin rapidly and selectively
      stimulates proteolytic processing of the nascent SREBP-1c by enhancing the
      affinity of the SREBP cleavage-activating protein (SCAP).SREBP-1c complex for
      coatomer protein complex II (COPII) vesicles. The SCAP.SREBP complex is retained
      in the ER by Insig proteins. We report here that insulin persistently stimulates
      controlled proteolysis of the nascent SREBP-1c by selectively reducing the level
      of Insig-2a protein via accelerated degradation of its cognate mRNA. Insulin
      enhanced the rate of turnover of Insig-2a mRNA via its 3'-untranslated region.
      Insulin-induced depletion of Insig-2a promotes association of the SCAP.SREBP-1c
      complex with COPII vesicles and subsequent migration to the Golgi where site-1
      and site-2 proteases process the nascent SREBP-1c. Consistent with this
      mechanism, experimental knockdown of Insig-2a expression with small interfering
      RNA mimicked insulin-induced proteolysis of the nascent SREBP-1c, whereas
      exogenous expression of Insig-2a in hepatocytes led to reduced intramembrane
      proteolysis of the newly synthesized SREBP-1c. The action of insulin on the
      processing of the nascent SREBP-1c via Insig-2a was highly selective, as
      proteolysis of the newly synthesized SREBP-2 remained unchanged under identical
      conditions. On the basis of these data, we propose that the stimulation of SREBP
      1c processing by insulin is mediated by a selective depletion of Insig-2a protein
      by promoting decay of its cognate mRNA. Thus, insulin-induced reduction in Insig
      2a protein leads to an enhanced export of the SCAP.SREBP-1c complex from ER to
      the Golgi.

PMID- 19759401
TI  - Characterization of the time course of the superior mesenteric, abdominal aorta,
      internal carotid and vertebral arteries blood flow response to the oral glucose
      challenge test using magnetic resonance imaging.
AB  - Blood flow to the splanchnic circulation increases postprandially which may cause
      a reduction in systemic and cerebral perfusion leading to postprandial syncope in
      the elderly who lack adequate cardiovascular reserve. We used multi-station 2D
      phase contrast cine magnetic resonance imaging (PC-MRI) with the aim of
      characterizing the time course of the haemodynamic response to an oral glucose
      challenge test (OGCT) in the large arteries perfusing the splanchnic, systemic
      and cerebral circulations (superior mesenteric artery SMA, abdominal aorta AA,
      internal carotid arteries, ICA and vertebral arteries VA). In this study nine
      fasted healthy volunteers were studied. Separate cine PC-MRI scans were acquired
      in the neck and in the abdomen every 88 s, these two measurements being
      interleaved for ten baseline scans at each station with the scanner automatically
      moving the subject between the two stations. After ingestion of the OGCT, a
      further 30 cine PC-MRI scans were acquired at each station. Using this technique
      we were able to characterize with frequent sampling of volumetric blood flow the
      time course of blood flow response to the OGCT of the SMA, AA and both VA and
      ICA. We found a substantial variation between individuals in the amplitude and
      the time to the peak of the SMA blood flow response to the OGCT which correlated
      positively with body mass index. MRI provides a robust, non-invasive method of
      studying normal physiology that could be valuable in studies of diseases such as
      postprandial hypotension.

PMID- 19759402
TI  - The application of particle filters in single trial event-related potential
      estimation.
AB  - In this paper, an approach for the estimation of single trial event-related
      potentials (ST-ERPs) using particle filters (PFs) is presented. The method is
      based on recursive Bayesian mean square estimation of ERP wavelet coefficients
      using their previous estimates as prior information. To enable a performance
      evaluation of the approach in the Gaussian and non-Gaussian distributed noise
      conditions, we added Gaussian white noise (GWN) and real electroencephalogram
      (EEG) signals recorded during rest to the simulated ERPs. The results were
      compared to that of the Kalman filtering (KF) approach demonstrating the
      robustness of the PF over the KF to the added GWN noise. The proposed method also
      outperforms the KF when the assumption about the Gaussianity of the noise is
      violated. We also applied this technique to real EEG potentials recorded in an
      odd-ball paradigm and investigated the correlation between the amplitude and the
      latency of the estimated ERP components. Unlike the KF method, for the PF there
      was a statistically significant negative correlation between amplitude and
      latency of the estimated ERPs, matching previous neurophysiological findings.

PMID- 19759403
TI  - Measurement of the modification and interference rate of urinary albumin detected
      by size-exclusion HPLC.
AB  - The measurement of the excretion of urinary albumin (albuminuria) is an important
      and well-established method to assess clinical outcomes. A high-performance
      liquid chromatography (HPLC) method has been introduced to measure albuminuria.
      Using this method, it was found that commonly used immunological methods do not
      measure a fraction of urinary albumin. Some authors presumed that the reason of
      immuno-unreactivity is the modification of urinary albumin; some others presumed
      that the difference is merely because of interference. In order to decide this
      question, we established an HPLC method equipped with tandem UV and fluorescent
      detection to assess the changes in the detectability of albumin with the rate of
      modification. For this measurement, differently modified forms of albumin were
      used. Urine samples of diabetic patients were also measured to find a potential
      connection between the modification rate and clinical parameters. Secondly, we
      have established a reversed phase HPLC method to assess the interference rate. We
      conclude that albumin modification does not affect immunoreactivity. The
      modification rate of urinary albumin in diabetic patients showed a correlation
      with renal function. The interference rate of the albumin peak was found to be
      12.7% on average, which does not explain the difference between the two methods.

PMID- 19759404
TI  - Evaluation of the dose enhancement of iodinated compounds by polyacrylamide gel
      dosimetry.
AB  - In this study, polyacrylamide gel (PAG) dosimetry is used to quantitatively
      assess the efficiency of radiation sensitizers. The local dose enhancement caused
      by the K-edge absorption of certain atoms such as bromine and iodine can be
      employed to increase the damage to neighboring molecules and cells. Clonogenic
      assays can assess the radiation survival of cells to evaluate the efficiency of
      radiation sensitizers, but this technique requires reliable cell growth in
      culture media and is time consuming. Our purpose is to use PAG dosimetry to
      investigate the sensitizing potential of radiation sensitizers such as iodinated
      compounds. Incorporation of iodinated radiation sensitizers such as NaI and an
      iodinated contrast agent leads to a quantifiable dose enhancement ratio. When
      irradiated at low energy (approximately 40 keV), the dose enhancement ratio of
      the iodinated contrast agent at concentrations of 0.01 (3.5 mg ml(-1)), 0.05 (6
      mg ml(-1)) and 0.1 (12 mg ml(-1)) M are 1.16 +/- 0.02, 1.39 +/- 0.03 and 1.82 +/-
      0.04, respectively. No dose enhancement was observed when the samples were
      irradiated with 1.25 MeV gamma photons.

PMID- 19759405
TI  - The effect of activity outside the field of view on image quality for a 3D LSO
      based whole body PET/CT scanner.
AB  - The purpose of this study was to quantify the influence of outside field of view
      (FOV) activity concentration (A(c)(,out)) on the noise equivalent count rate
      (NECR), scatter fraction (SF) and image quality of a 3D LSO whole-body PET/CT
      scanner. The contrast-to-noise ratio (CNR) was the figure of merit used to
      characterize the image quality of PET scans. A modified International
      Electrotechnical Commission (IEC) phantom was used to obtain SF and counting
      rates similar to those found in average patients. A scatter phantom was
      positioned at the end of the modified IEC phantom to simulate an activity that
      extends beyond the scanner. The modified IEC phantom was filled with (18)F (11
      kBq mL(-1)) and the spherical targets, with internal diameter (ID) ranging from
      10 to 37 mm, had a target-to-background ratio of 10. PET images were acquired
      with background activity concentrations into the FOV (A(c)(,bkg)) about 11, 9.2,
      6.6, 5.2 and 3.5 kBq mL(-1). The emission scan duration (ESD) was set to 1, 2, 3
      and 4 min. The tube inside the scatter phantom was filled with activities to
      provide A(c)(,out) in the whole scatter phantom of zero, half, unity, twofold and
      fourfold the one of the modified IEC phantom. Plots of CNR versus the various
      parameters are provided. Multiple linear regression was employed to study the
      effects of A(c)(,out) on CNR, adjusted for the presence of variables (sphere ID,
      A(c)(,bkg) and ESD) related to CNR. The presence of outside FOV activity at the
      same concentration as the one inside the FOV reduces peak NECR of 30%. The
      increase in SF is marginal (1.2%). CNR diminishes significantly with increasing
      outside FOV activity, in the range explored. ESD and A(c)(,out) have a similar
      weight in accounting for CNR variance. Thus, an experimental law that adjusts the
      scan duration to the outside FOV activity can be devised. Recovery of CNR loss
      due to an elevated A(c)(,out) activity seems feasible by modulating the ESD in
      individual bed positions according to A(c)(,out).

PMID- 19759406
TI  - In vivo electrical conductivity measurements during and after tumor
      electroporation: conductivity changes reflect the treatment outcome.
AB  - Electroporation is the phenomenon in which cell membrane permeability is
      increased by exposing the cell to short high-electric-field pulses. Reversible
      electroporation treatments are used in vivo for gene therapy and drug therapy
      while irreversible electroporation is used for tissue ablation. Tissue
      conductivity changes induced by electroporation could provide real-time feedback
      of the treatment outcome. Here we describe the results from a study in which
      fibrosarcomas (n = 39) inoculated in mice were treated according to different
      electroporation protocols, some of them known to cause irreversible damage.
      Conductivity was measured before, within the pulses, in between the pulses and
      for up to 30 min after treatment. Conductivity increased pulse after pulse.
      Depending on the applied electroporation protocol, the conductivity increase
      after treatment ranged from 10% to 180%. The most significant conclusion from
      this study is the fact that post-treatment conductivity seems to be correlated
      with treatment outcome in terms of reversibility.

PMID- 19759407
TI  - A method of adaptive wavelet filtering of the peripheral blood flow oscillations
      under stationary and non-stationary conditions.
AB  - The paper describes an original method for analysis of the peripheral blood flow
      oscillations measured with the laser Doppler flowmetry (LDF) technique. The
      method is based on the continuous wavelet transform and adaptive wavelet theory
      and applies an adaptive wavelet filtering to the LDF data. The method developed
      allows one to examine the dynamics of amplitude oscillations in a wide frequency
      range (from 0.007 to 2 Hz) and to process both stationary and non-stationary
      short (6 min) signals. The capabilities of the method have been demonstrated by
      analyzing LDF signals registered in the state of rest and upon humeral occlusion.
      The paper shows the main advantage of the method proposed, which is the
      significant reduction of 'border effects', as compared to the traditional wavelet
      analysis. It was found that the low-frequency amplitudes obtained by adaptive
      wavelets are significantly higher than those obtained by non-adaptive ones. The
      method suggested would be useful for the analysis of low-frequency components of
      the short-living transitional processes under the conditions of functional tests.
      The method of adaptive wavelet filtering can be used to process stationary and
      non-stationary biomedical signals (cardiograms, encephalograms, myograms, etc),
      as well as signals studied in the other fields of science and engineering.

PMID- 19759408
TI  - Measurements of attenuation coefficient for evaluating the hardness of a cataract
      lens by a high-frequency ultrasonic needle transducer.
AB  - A cataract is a clouding of the lens in the eye that affects vision.
      Phacoemulsification is the mostly common surgical method for treating cataracts,
      and determining that the optimal phacoemulsification energy is dependent on
      measuring the hardness of the lens. This study explored the use of an ultrasound
      needle transducer for invasive measurements of ultrasound attenuation coefficient
      to evaluate the hardness of the cataract lens. A 47 MHz high-frequency needle
      transducer with a diameter of 0.9 mm was fabricated by a polarized PMN-33%PT
      single crystal in the present study. The attenuation coefficients at different
      stages of an artificial porcine cataract lens were measured using the spectral
      shift approach. The hardness of the cataract lens was also evaluated by
      mechanical measurement of its elastic properties. The results demonstrated that
      the ultrasonic attenuation coefficient was increased from 0.048 +/- 0.02 to 0.520
      +/- 0.06 dB mm(-1) MHz(-1) corresponding to an increase in Young's modulus from 6
      +/- 0.4 to 96 +/- 6.2 kPa as the cataract further developed. In order to evaluate
      the feasibility of combining needle transducer and phacoemulsification probe for
      real-time measurement during cataract surgery, the needle transducer was mounted
      on the phacoemulsification probe for a vibration test. The results indicated that
      there was no apparent damage to the tip of the needle transducer and the pulse
      echo test showed that a good performance in sensitivity was maintained after the
      vibration test.

PMID- 19759409
TI  - A Kramers-Kronig-based quality factor for shear wave propagation in soft tissue.
AB  - Shear wave propagation techniques have been introduced for measuring the
      viscoelastic material properties of tissue, but assessing the accuracy of these
      measurements is difficult for in vivo measurements in tissue. We propose using
      the Kramers-Kronig relationships to assess the consistency and quality of the
      measurements of shear wave attenuation and phase velocity. In ex vivo skeletal
      muscle we measured the wave attenuation at different frequencies, and then
      applied finite bandwidth Kramers-Kronig equations to predict the phase
      velocities. We compared these predictions with the measured phase velocities and
      assessed the mean square error (MSE) as a quality factor. An algorithm was
      derived for computing a quality factor using the Kramers-Kronig relationships.

PMID- 19759410
TI  - Evaluation of quantitative planar 90Y bremsstrahlung whole-body imaging.
AB  - With high-dose administration of (90)Y labeled antibodies, it is possible to
      image (90)Y without an admixture of (111)In. We have earlier shown that it is
      possible to perform quantitative (90)Y bremsstrahlung SPECT for dosimetry
      purposes with reasonable accuracy. However, whole-body (WB) activity
      quantification with the conjugate view method is not as time consuming as SPECT
      and has been the method of choice for dosimetry. We have investigated the
      possibility of using a conjugate view method where scatter-, backscatter- and
      septal-penetration compensations are performed by inverse filtering and
      attenuation correction is performed with a WB x-ray image, for total-body and
      organ activity quantification of (90)Y. The method was evaluated using both Monte
      Carlo simulated scintillation camera images using realistic source distributions,
      and by an experimental phantom study. The method was evaluated in terms of image
      quality and accuracy of the activity quantification. The experimental phantom
      study was performed using the RSD torso phantom with (90)Y activity uniformly
      distributed in the liver insert. A GE Discovery VH/Hawkeye system was used to
      acquire the image. The simulation study was performed for a realistic activity
      distribution in the NCAT anthropomorphic phantom where (90)Y bremsstrahlung
      images were generated using the SIMIND MC program. Two different phantom
      configurations and two activity distributions were simulated. To mimic the RSD
      phantom experiment one simulation study was also made with (90)Y activity located
      only in the liver. The SIMIND program was configured to resemble a GE Discovery
      VH/Hawkeye system. An x-ray projector program was used to generate whole-body x
      ray images from the NCAT phantom for attenuation correction in the conjugate view
      method. Organ activities were calculated from ROIs that exactly covered the
      organs. Corrections for background activity, overlapping activity and source
      extension in the depth direction were applied on the ROI data. The total-body
      activities for the simulated images were generally overestimated by around 10%,
      which is reasonable since the correction for source extension was not applied on
      the total-body values. The accuracy of the organ activities was mostly within 15%
      for both the simulation study and the experimental study. The results suggest
      that it is possible to quantify (90)Y activity in ROIs with reasonable accuracy
      using this method.

PMID- 19759411
TI  - The discrepancy between human peripheral nerve chronaxie times as measured using
      magnetic and electric field stimuli: the relevance to MRI gradient coil safety.
AB  - Peripheral nerve stimulation (PNS) resulting from electric fields induced from
      the rapidly changing magnetic fields of gradient coils is a concern in MRI.
      Nerves exposed to either electric fields or changing magnetic fields would be
      expected to display consistent threshold characteristics, motivating the direct
      application of electric field exposure criteria from the literature to guide the
      development of gradient magnetic field exposure criteria for MRI. The consistency
      of electric and magnetic field exposures was tested by comparing chronaxie times
      for electric and magnetic PNS curves for 22 healthy human subjects. Electric and
      magnetic stimulation thresholds were measured for exposure of the forearm using
      both surface electrodes and a figure-eight magnetic coil, respectively. The
      average chronaxie times for the electric and magnetic field conditions were 109
      +/- 11 micros and 651 +/- 53 micros (+/-SE), respectively. We do not propose that
      these results call into question the basic mechanism, namely that rapidly
      switched gradient magnetic fields induce electric fields in human tissues,
      resulting in PNS. However, this result does motivate us to suggest that special
      care must be taken when using electric field exposure data from the literature to
      set gradient coil PNS safety standards in MRI.

PMID- 19759412
TI  - RPI-AM and RPI-AF, a pair of mesh-based, size-adjustable adult male and female
      computational phantoms using ICRP-89 parameters and their calculations for organ
      doses from monoenergetic photon beams.
AB  - This paper describes the development of a pair of adult male and adult female
      computational phantoms that are compatible with anatomical parameters for the
      50th percentile population as specified by the International Commission on
      Radiological Protection (ICRP). The phantoms were designed entirely using
      polygonal mesh surfaces--a Boundary REPresentation (BREP) geometry that affords
      the ability to efficiently deform the shape and size of individual organs, as
      well as the body posture. A set of surface mesh models, from Anatomium 3D P1
      V2.0, including 140 organs (out of 500 available) was adopted to supply the basic
      anatomical representation at the organ level. The organ masses were carefully
      adjusted to agree within 0.5% relative error with the reference values provided
      in the ICRP Publication 89. The finalized phantoms have been designated the RPI
      adult male (RPI-AM) and adult female (RPI-AF) phantoms. For the purposes of organ
      dose calculations using the MCNPX Monte Carlo code, these phantoms were
      subsequently converted to voxel formats. Monoenergetic photons between 10 keV and
      10 MeV in six standard external photon source geometries were considered in this
      study: four parallel beams (anterior-posterior, posterior-anterior, left lateral
      and right lateral), one rotational and one isotropic. The results are tabulated
      as fluence-to-organ-absorbed-dose conversion coefficients and fluence-to
      effective-dose conversion coefficients and compared against those derived from
      the ICRP computational phantoms, REX and REGINA. A general agreement was found
      for the effective dose from these two sets of phantoms for photon energies
      greater than about 300 keV. However, for low-energy photons and certain
      individual organs, the absorbed doses exhibit profound differences due to
      specific anatomical features. For example, the position of the arms affects the
      dose to the lung by more than 20% below 300 keV in the lateral source directions,
      and the vertical position of the testes affects the dose by more than 80% below
      150 keV in the PA source direction. The deformability and adjustability of organs
      and posture in the RPI adult phantoms may prove useful not only for average
      workers or patients for radiation protection purposes, but also in studies
      involving anatomical and posture variability that is important in future
      radiation protection dosimetry.

PMID- 19759413
TI  - A panel of high resolution melting (HRM) technology-based assays with direct
      sequencing possibility for effective mutation screening of EGFR and K-ras genes.
AB  - BACKGROUND: Increasing data from clinical trials support EGFR and K-ras mutation
      status as predictive markers of tumour response to EGFR-targeted therapies.
      Consequently, rapid and reliable mutation screening assays are demanded to guide
      rational use of EGFR-targeted therapies. METHODS: In this study, we describe the
      development of high resolution melting (HRM) technology-based assays with direct
      sequencing confirmation possibility for mutation screening of the EGFR gene
      (exons 19, 20 and 21) in routine diagnostic specimens, and compared assay
      findings to those of conventional nested-PCR following cycle-sequencing. RESULTS:
      In reconstruction experiments, each HRM assay following sequencing demonstrated a
      sensitivity of < or =5% of mutated DNA in a background of wild-type DNA. The
      panel of EGFR HRM assays following sequencing applied to a series of genomic DNA
      samples isolated from 68 FFPE NSCLC specimens correctly identified all EGFR
      mutations that were previously found by nested-PCR following cycle-sequencing.
      The HRM approach additionally scored two mutations not detected by the
      conventional assay. Complementary HRM following sequencing for K-ras revealed
      three mutations. EGFR and K-ras mutations were mutually exclusive. CONCLUSIONS:
      The panel of designed HRM assays with direct reflex sequencing possibility
      provides an effective method for mutation screening of EGFR and K-ras genes in
      routine diagnostic specimens, thereby allowing the selection of the treatment of
      choice in clinical practice.

PMID- 19759414
TI  - LOH at 1p31 (ARHI) and proliferation in lymph node-negative breast cancer.
AB  - BACKGROUND: The mitotic activity index (MAI) is a strong prognosticator in node
      negative invasive breast cancer patients. Recently, a correlation between the MAI
      and specific chromosomal aberrations at chromosome 1p was described. METHODS:
      Analysis of MAI, immunohistochemical staining patterns for proliferation
      associated phosphohistone H3 (PPH3), phosphorylated ERK1/2, p21, cyclin E, Ki67
      and cyclin D1 proteins; and prognosis in 158 adjuvant chemotherapy-treated T1
      2N0M0 invasive breast cancer patients, analysis of LOH at 1p31 (including ARHI)
      using the dinucleotide repeats D1S207, D1S430 and D1S464 in 76 patients. Single
      and multivariate survival analysis was used to evaluate the importance of the
      various markers tested. RESULTS: LOH at 1p31 did not correlate with MAI nor
      provide prognostic information. Phosphohistone H3 was the best prognosticator for
      patients in all age groups with 20 year distant metastasis free survival of
      distant metastases 93% vs. 72% respectively (p=0.004, HR=4.5). In multivariate
      analysis, phosphohistone H3<13 vs. > or =13 exceeded the prognostic value of the
      mitotic activity index. CONCLUSIONS: LOH at 1p31 is common in breast cancer, and
      correlates with loss of proliferation-associated proteins, but not with MAI, PPH3
      or prognosis. PPH3 is the best prognosticator in this study group of adjuvant
      chemotherapy-treated lymph node-negative breast cancer patients.

PMID- 19759415
TI  - Pla2g2a attenuates colon tumorigenesis in azoxymethane-treated C57BL/6 mice;
      expression studies reveal Pla2g2a target genes and pathways.
AB  - BACKGROUND: The group IIA secretory phospholipase A2 gene, Pla2g2a, confers
      resistance to intestinal tumorigenesis in the Apc(Min/+) mouse model. However, it
      is unclear how Pla2g2a exerts its tumor-suppressive effects and whether its mode
      of action depends on Apc-germline mutations. METHODS: We tested whether
      expression of a Pla2g2a transgene provides protection against carcinogen-induced
      colon tumors, and examined whether the normal colon microenvironment is modulated
      by Pla2g2a expression. RESULTS: Pla2g2a strongly inhibited colon tumorigenesis in
      mice following treatment with the DNA alkylating agent azoxymethane (AOM).
      Moreover, AOM-induced duodenal tumors were also attenuated by Pla2g2a expression.
      These tumors demonstrated upregulation of beta-catenin, indicative of involvement
      of the Wnt signaling pathway. Comparison of genome-wide microarray expression
      profiles of healthy (non-pathologic) colon tissues from Pla2g2a-transgenic to non
      transgenic mice revealed 382 genes that were differentially expressed, comprising
      clusters of genes involved in inflammation and microbial defense, cell signaling
      and cell cycle, transactivation, apoptosis and mitochondrial function, DNA
      repair, and lipid and energy metabolism. Pathway analysis using Gene Set
      Enrichment Analysis (GSEA) indicated that Pla2g2a suppresses the expression of
      interferon-induced genes. CONCLUSION: Our results demonstrate that Pla2g2a
      attenuates colon tumorigenesis independent of Apc-germline mutations, and reveal
      Pla2g2a target genes and pathways in non-pathologic colon microenvironment that
      influence conditions for colorectal cancer development.

PMID- 19759416
TI  - Multiple localization of endogenous MARK4L protein in human glioma.
AB  - BACKGROUND: We have previously shown that the sustained expression of MARK4L
      transcripts in glioma and neural progenitors (NHNPs) declines after exposure to
      antisense MARK4L oligonucleotides in glioblastoma cell lines. Array-CGH confirmed
      the genomic duplication of MARK4L identified by FISH in a glioblastoma cell line.
      This background together with literature data on the exogenous association of
      MARK4 with interphase centrosome prompted us to investigate the sub-cellular
      localization of the endogenous MARK4L protein aiming at achieving insights on its
      possible role in the pathomechanisms of glioma. METHODS: Immunodetection was
      carried out to validate the specificity of MARK4L antibody in gliomas and NHNPs.
      Mass spectrometry was applied for MARK4L protein identification in a
      representative glioblastoma cell line. Combined biochemical fractionation and
      immunodetection analyses were performed to confirm the sub-cellular localization
      of MARK4L achieved by immunofluorescence in glioma cell lines. RESULTS: By
      assigning MARK4L protein within the band immunoprecipitated by the specific
      antibody we validated our anti-MARK4L antibody. We demonstrated that the
      endogenous MARK4L: (i) colocalizes with centrosomes at all mitotic stages and
      resides in centrosome-enriched fractions; (ii) associates with the nucleolus and
      the midbody and respective fractions, and (iii) co-stains the aberrant centrosome
      configurations observed in glioma cell lines. CONCLUSION: The overall data merge
      on the multiplex entry of MARK4L into the cell cycle and link it to the aberrant
      centrosomes in glioma cell lines suggesting a possible role of this kinase in the
      abnormal mitotic processes of human glioma.

PMID- 19759417
TI  - Different angiogenic potential in low and high grade sporadic clear cell renal
      cell carcinoma is not related to alterations in the von Hippel-Lindau gene.
AB  - BACKGROUND: von Hippel-Lindau (VHL) inactivation is common in sporadic clear cell
      renal cell carcinomas (ccRCC). pVHL is part of the ubiquitin ligase complex that
      targets the alpha subunits of hypoxia-inducible transcription factor (HIF) for
      degradation under well-oxygenated conditions. In the absence of wild-type pVHL,
      as observed in VHL patients and most sporadic ccRCCs, constitutive upregulation
      of HIF results in transcriptional activation of angiogenesis-related genes, such
      as VEGF. Differences in angiogenic activity within the group of ccRCCs were
      reported and strong genotype-phenotype correlations were found in patients with
      VHL disease, raising a question about the importance of VHL inactivation status
      in angiogenic behaviour and tumour progression. METHODS: To address this
      question, we investigated the influence of VHL mutation (direct
      sequencing)/hypermethylation (methylation-specific PCR) on angiogenesis/tumour
      parameters (immunohistochemistry) in 150 patients with sporadic ccRCC. RESULTS:
      We found no significant association between VHL mutation or methylation and
      angiogenesis/tumour parameters. CONCLUSION: These data indicate that tumour
      progression and angiogenesis are not directly influenced by VHL alterations and
      that additional genetic/epigenetic events should be considered to explain the
      diverse angiogenic and proliferative behaviour during tumour progression.

PMID- 19759418
TI  - Protein oxidation in breast microenvironment: Nipple aspirate fluid collected
      from breast cancer women contains increased protein carbonyl concentration.
AB  - BACKGROUND: Protein carbonyl levels are the most frequently used biomarker of
      protein oxidation in several human diseases, including cancer. Breast cancer, a
      worldwide disease with increasing incidence, develops from ductal/lobular
      epithelium from which nipple aspirate fluid can be collected and analysed to
      assess tissue metabolic activity. Our aims were to perform an exploratory
      investigation on the protein carbonyl accumulation in breast secretions from
      healthy and cancer patients and its correlation with lipid peroxidation markers.
      METHODS: Protein carbonyls were determined by ELISA in 288 Nipple Aspirate Fluids
      (NAF) from Control, Pre-malignant and Cancer patients. RESULTS: Significantly
      higher protein carbonyl concentration was found in NAF from breast cancer (BC)
      patients compared to Control subjects. Cancer patients accumulated in NAF
      significantly higher levels of carbonyls in post-menopausal condition. A
      significant inverse relationship between carbonyls and 8-F2alpha-isoprostanes in
      NAF was found in Cancer patients. NAF levels of protein carbonyls are
      significantly higher in women with pre-malignant conditions than in healthy
      subjects. CONCLUSION: Our results support the hypothesis that oxidative stress in
      breast microenvironment plays a role in breast cancer; measurement of protein and
      lipid oxidative products in NAF may improve the identification of women at
      increased breast cancer risk.

PMID- 19759419
TI  - Dual function microtubule- and mitochondria-associated proteins mediate mitotic
      cell death.
AB  - BACKGROUND: Survival and evolution of aneuploid cells after an asymmetric
      segregation of chromosomes at mitosis may be the common initiating event and
      underlying cause of the genetic diversity and adaptability of cancers. We
      hypothesize that mechanisms exist to detect impending aneuploidy and prevent it
      before completion of an aberrant mitosis. METHODS: The distribution of isoforms
      of C19ORF5, an interactive partner with mitochondria-associated LRPPRC and tumor
      suppressor RASSF1A, state of spindle microtubules and mitochondrial aggregation
      was analyzed in synchronized mitotic cells and cells stalled in mitosis after
      treatment with paclitaxel. RESULTS: C19ORF5 distributed broadly across the
      mitotic spindle and reversibly accumulated during reversible mitotic arrest.
      Prolonged stabilization of microtubules caused an accumulation of a C19ORF5
      product with dual MAP and MtAP properties that caused irreversible aggregation of
      mitochondria and death of mitotic cells. CONCLUSION: Dual function microtubule
      associated (MAP) and mitochondria-associated (MtAP) proteins generated by
      prolonged mitotic arrest trigger mitochondrial-induced mitotic cell death. This
      is a potential mechanism to prevent minimal survivable aneuploidy resulting from
      an aberrant cell division and cancers in general at their earliest common origin.

PMID- 19759420
TI  - Absence of Granzyme B positive tumour-infiltrating lymphocytes in primary
      melanoma excisional biopsies is strongly associated with the presence of sentinel
      lymph node metastasis.
AB  - BACKGROUND: Sentinel Lymph Node (SLN) status is strongly related to clinical
      outcome in melanoma patients. In this study we investigated the possible
      association between the presence of activated and/or suppressive Tumour
      Infiltrating Lymphocytes (TILs) and SLN status in clinically stage I/II melanoma
      patients. METHODS: Diagnostic primary melanoma samples from 20 patients with a
      sentinel lymph node metastasis were compared to melanoma samples from 20 patients
      with a negative sentinel lymph node, who were matched for gender, age and Breslow
      thickness. Presence of activated Granzyme B positive (GrB+) TILs, presence of
      suppressive (FoxP3+) TILs and MHC class I antigen expression on tumour cells were
      analysed by immunohistochemistry. RESULTS: FoxP3 and MHC-I expression had no
      direct bearing on the presence of melanoma metastases in the SLN. Whereas the
      presence of activated GrB+ TILs in the primary melanoma had no predictive value
      for SLN status either, their absence was strongly associated with the presence of
      metastasis in the SLN (p=0.001). While both GrB+ and FoxP3+ TILs could be
      detected in SLN metastases, a majority did not display MHC-I expression.
      CONCLUSION: These data support a role for cytotoxic T cells in the prevention of
      early metastasis of melanoma to the draining lymph nodes.

PMID- 19759421
TI  - From the editor.

PMID- 19759422
TI  - The clinical utility of functional capacity evaluations: the opinion of health
      professionals working within occupational rehabilitation.
AB  - Functional Capacity Evaluations (FCE's) are used within the occupational
      rehabilitation arena with the aim of assessing an individual's functional
      abilities in relation to work tasks. Therapists use a variety of different FCE's,
      both standardized and non standardized. This study aimed to investigate
      therapists' views on the clinical utility of FCE's in general and to identify if
      these differed between professional groups. A cross sectional study design was
      used. Health professionals who conduct FCE's and who worked for WorkCover
      accredited rehabilitation providers in NSW were surveyed. Surveys were returned
      from 79 participants working for 65 different rehabilitation providers. Of those
      who replied, 82?% (n=63) were occupational therapists, 13% (n=10)
      physiotherapists and 5% (n=5) exercise physiologists. The mean years of
      professional experience was 10.9 years and the mean years of FCE experience was
      5.3 years. Data were analyzed using STATA [v8.0] and the clinical utility of
      FCE's was considered relating to: usefulness & relevance; adaptability and
      flexibility; therapist perceived requirements and issues in practice. No
      differences were found related to the clinical utility of FCE's between
      professional groups or years of professional experience. The results suggest
      consistency and similarities in how FCE's are currently used in practice across
      NSW (Australia). Limitations of this study and areas for further research are
      suggested.

PMID- 19759423
TI  - Therapy practice within a minimal lift environment: perceptions of therapy staff.
AB  - The purpose of this research was to explore the perceptions of occupational and
      physical therapy staff regarding a minimal lift policy implemented in a
      midwestern health system. Researchers used a qualitative focus group approach,
      facilitating four focus groups with 23 members of the hospital therapy staff.
      Transcripts of the focus groups were coded and analyzed for emergent themes.
      Several themes emerged from the data: Therapist risk of injury, Attitudes towards
      and use of equipment, Professional relationships and teamwork, and Effectiveness
      of minimal lift programs: barriers and supports. In general, therapists felt they
      were susceptible to work-related injury because of the nature of their work,
      environmental factors, and the actions of others. The therapists served as
      trainers in the minimal lift program. They trained other staff in equipment use;
      were resources for staff on the floors; and they used the equipment in the
      context of therapeutic intervention. Equipment was seen as useful primarily for
      the rehabilitation of low functioning or bariatric patients. Further research
      about the design and effect of equipment in therapy is recommended.

PMID- 19759424
TI  - Lifestyle determinants of depressive feeling and a feeling of unhappiness among
      workers: a study in Japan.
AB  - BACKGROUND: Lifestyle determinants of depressive state and a feeling of
      unhappiness in daily life were evaluated among the workers in Japan by adjusting
      obesity and age. METHODS: A total of 3630 men aged 34 to 60 years from a
      workplace in Japan participated in this cross-sectional study conducted in 2006.
      The prevalence of depressive state and a feeling of unhappiness were evaluated by
      a questionnaire with questions pertaining to the age, body mass index, and six
      lifestyle factors. The six lifestyle factors were frequency of exercise and
      alcohol intake per week, smoking habit, hours of sleep per day, and frequency of
      eating breakfast and snack per week. The associations between depressive state
      and/or a feeling of unhappiness and the lifestyle factors were tested by logistic
      regression analysis. RESULTS: The prevalence of depressive state and a feeling of
      unhappiness among the workers was 8.1% and 20.3%, respectively. The prevalence of
      workers who sleep at least for 6 hours on average, exercise regularly and eat
      breakfast everyday increased as the age of the workers increased. Depressive
      state and a feeling of unhappiness were significantly associated with age and a
      reduced duration of sleep even after adjustment for the other variables. No
      significant associations were found between the other lifestyle factors examined
      and depressive state and/or a feeling of unhappiness. CONCLUSIONS: Depressive
      state and/or a feeling of unhappiness were significantly associated with a
      reduced duration of sleep among the workers. Aging was a preventative factor of
      depressive state and/or a feeling of unhappiness. The effect of obesity was
      adjusted in this study, but the cause-effect relation between lifestyles and
      depressive state and/or a feeling of unhappiness should be clarified by the
      follow-up study.

PMID- 19759425
TI  - Older workers: an exploration of the benefits, barriers and adaptations for older
      people in the workforce.
AB  - The continuation of older people in the paid workforce is regarded as beneficial
      for both the economy and older workers. While there have been attempts to
      encourage older people to continue working, little is understood about older
      workers' perspectives. This qualitative study explored the lived experiences and
      perceptions of paid workers aged 60 years and older with the aim of understanding
      why older people continue to work and the barriers and facilitators they
      encounter. Sixteen older Australians (eight males and eight females, mean age 67
      years) who participated in paid employment for at least 12 hours per month were
      interviewed. Thematic analysis elicited themes of benefits of work, problems
      encountered at work and the ways in which older people respond to these
      challenges. Financial considerations, the desire to contribute and the absence of
      competing interests were reasons given for continuing involvement in work. Older
      workers identified stress, lack of support, physical demands and overemphasis on
      qualifications as barriers to their participation. Maintaining a healthy
      lifestyle, having a passion for work, and education were factors that
      participants identified as supporting continued work. These findings enhance the
      understanding of the experiences of older workers and may have implications for
      encouraging workforce participation of older people.

PMID- 19759426
TI  - A behavioral approach to RTW after sickness absence: the development of
      instruments for the assessment of motivational determinants, motivation and key
      actors' attitudes.
AB  - INTRODUCTION: On the basis of a motivational framework for return to work (RTW)
      after sickness absence, scales were developed to measure absentee attitudes
      towards RTW, perceived social norm with respect to RTW, RTW self-efficacy, RTW
      motivation, and the RTW attitudes of six types of key actors. METHODS: Both
      theory and 33 in-depth interviews with sickness absentees and occupational
      physicians produced 95 items. A sample of 119 absentees who had reported sick for
      more than one month completed these items. Absentees varied with respect to
      gender, age, educational level, and work sector. RESULTS: Factor analyses and
      reliability analyses yielded seventeen scales with sufficient reliability
      (Cronbach's alpha: 0.60-0.86). CONCLUSIONS: The new scales appear to be valid and
      promising for future research on RTW. Validation in larger samples is necessary
      and the predictive validity should to be tested.

PMID- 19759427
TI  - Predictors of work presence--sickness absence in a salutogenic perspective.
AB  - The objective of the study was to identify determinants of work presence, i.e.
      factors that counteract short and/or long term sickness absence. The analyses
      were based on logistic regression analyses on Swedish regional survey data.
      Individuals who had not reported sickness absence during the preceding year were
      compared to on one hand individuals with short term sickness absence (< 28 days)
      and on the other hand with long term sickness absence (> 28 days). We found
      predictors of work presence in personal background as well as in work related
      variables. A high level of sense of coherence was found to counteract short as
      well as long term sickness absence. Gender specific differences were observed.
      Although a set of predictors common for the short and long term perspective were
      found the predictors in general were found to differentiate substantially with
      respect to short or long term sickness absence. Implications for sickness absence
      prevention and health promotion could be drawn from the results. Primarily
      different aspects of control over working situation, work satisfaction and for
      women a high level of sense of coherence were believed to have these
      implications.

PMID- 19759428
TI  - Effect of yoga on musculoskeletal discomfort and motor functions in professional
      computer users.
AB  - The self-rated musculoskeletal discomfort, hand grip strength, tapping speed, and
      low back and hamstring flexibility (based on a sit and reach task) were assessed
      in 291 professional computer users. They were then randomized as Yoga (YG; n=146)
      and Wait-list control (WL; n=145) groups. Follow-up assessments for both groups
      were after 60 days during which the YG group practiced yoga for 60 minutes daily,
      for 5 days in a week. The WL group spent the same time in their usual
      recreational activities. At the end of 60 days, the YG group (n=62) showed a
      significant decrease in the frequency, intensity and degree of interference due
      to musculoskeletal discomfort, an increase in bilateral hand grip strength, the
      right hand tapping speed, and low back and hamstring flexibility (repeated
      measures ANOVA and post hoc analysis with Bonferroni adjustment). In contrast,
      the WL group (n=56) showed an increase in musculoskeletal discomfort and a
      decrease in left hand tapping speed. The results suggest that yoga practice is a
      useful addition to the routine of professional computer users.

PMID- 19759429
TI  - Safety and ergonomic considerations for an aging workforce in the US construction
      industry.
AB  - The US construction workforce is aging as millions of baby boomers move toward
      retirement age. Older workers make a substantial contribution to construction in
      terms of skills and experience. However, construction is still one of the most
      physically demanding occupations, hence the health implications for older
      workers. Descriptions of injuries, illnesses and fatalities among older workers
      in the US construction industry from recent literature are presented along with
      the practical health and safety interventions that have been proposed including:
      ergonomic interventions, wellness programs, worksite housekeeping, training, and
      safety climate. Understanding the risks and hazards in specific industries could
      help identify training and intervention requirements to meet the challenges
      facing aging workers in these occupational groups.

PMID- 19759430
TI  - Predictive factors of sustained return to work for persons with musculoskeletal
      disorders who participated in rehabilitation.
AB  - Musculoskeletal disorders (MSD) account for the majority of total morbidity cases
      in the working-age Swedish population. These disorders are thought to be the
      reason given for one-third of total certified sick leave requests. In addition to
      the high cost to society, MSD involve both physical and emotional suffering, pain
      and financial and social problems for the injured persons. The aim of this study
      was to identify predictive multidimensional factors for sustainable return to
      work (RTW) in a long-term follow-up persons with MSD. During the period 1992
      1999, 385 persons participated in a rehabilitation program. Ten years later, 354
      of these took part in a prospective follow-up study. The average post
      rehabilitation time was ten years (range=7-13 years) and 243 persons (69%)
      completed a questionnaire. The "working full-time" group (n=110) and the "sick
      listed" group (n=73) were included in the study. The two groups were compared in
      terms of predictors for RTW. Multiple stepwise logistic regression and bivariate
      analysis, as well as parametric and non-parametric tests, were used to identify
      predictive factors. The number of sick-listed days before rehabilitation, age,
      self-rated pain, life events, gender, physical capacity, self-rated functional
      capacity, educational level and light physical labor were predictors of long-term
      RTW. Return to work an be facilitated by planning at an early stage of the
      certified sick leave period using instrument that take these predictors into
      account.

PMID- 19759431
TI  - Correlation between work concentration level and background music: a pilot study.
AB  - It is a common phenomenon for office workers {to listen to music} while executing
      daily routines at their desks. The aim of this study was to investigate the
      correlation between work concentration level and background music. This research
      would first follow examples in previous researches, and then explore the
      influence of background music on participants' scores on attention tests. We hope
      to gain a preliminary understanding of the possible influence of background music
      on people's focus and concentration when doing work. Thirty-two college students
      were separated into three controlled groups; all were given the attention test.
      Group [a] listened to background music while being tested for 10 minutes; group
      [b] had no background music at all; and group [c] listened to the music for 10
      minutes prior to the attention test. The test was conducted in a "noise free"
      environment. The means and error rates for each group were then calculated. The
      findings showed that, in comparison with "no music at all", those who listened to
      music prior to testing obtained higher scores in attentiveness (most probably a
      supplemental effect of the music), whereas those who listened to music during
      attention test showed extremely high level of variation in attention test
      scoring. Background music does affect people's job-site behavior. In fact, all
      three test conditions - no background music at all, background music before the
      work shift, and background music during work - have affected worker performance
      on different levels.

PMID- 19759432
TI  - The HADRIAN approach to accessible transport.
AB  - This paper describes research carried out at Loughborough University in the UK
      into the areas of 'design for all' and accessible transport. The research
      addresses two common needs for designers and ergonomists working towards
      developing more inclusive products and environments, namely data on users that is
      accessible, valid, and applicable and a means of utilising the data to assess the
      accessibility of designs during the early stages of development. HADRIAN is a
      computer-based inclusive design tool that has been developed to support designers
      in their efforts to develop products that meet the needs of a broader range of
      users. Currently HADRIAN is being expanded to support transport design. This
      includes data on an individual's ability to undertake a variety of transport
      related tasks, such as vehicle ingress/egress, coping with uneven surfaces,
      steps, street furniture and complex pedestrian environments. The subsequent use
      of this data will be supported either through a task analysis system that will
      allow a designer to evaluate a design for a part of the transport infrastructure
      (ticket barrier, train carriage etc.), or alternatively allow the designer or an
      end user to evaluate a whole journey. The 'journey planner' feature of the
      HADRIAN tool will compare an individual's physical, cognitive and emotional
      abilities with the demands placed upon that individual by the mode(s) of
      transport available and the route options selected. It is envisaged that these
      developments will prove extremely useful to users, designers, planners and all
      those involved with transport use and implementation.

PMID- 19759433
TI  - Hospitalization for lifestyle related diseases in long haul drivers compared with
      other truck drivers and the working population at large.
AB  - Personal lifestyle and working conditions are closely linked for long haul truck
      drivers. We compare lifestyle related diseases in long haul drivers with other
      drivers of goods and the working population at large. Standardized hospital
      treatment ratios (SHR) for lifestyle related diseases were compared for long haul
      truck drivers and other truck drivers to the working population at large. The
      follow up group comprised of 2,175 long haul drivers and 15,060 other truck
      drivers. An increased risk was found for lifestyle related diseases among truck
      drivers except for alcohol related diseases. We identified a strong association
      between hospital treatment for obesity and working as a driver and an association
      between diabetes and working as a driver. No major differences in lifestyle
      related diseases were found in long haul drivers compared to other truck drivers
      with the exception of a significant lower risk for alcohol-related diseases and a
      possibly higher risk for lung cancer in long haul drivers. It is concluded that
      diseases related to excess caloric intake or lack of exercise may be a problem
      for truck drivers. This risk is preventable and of importance both in
      occupational medicine as in public health.

PMID- 19759434
TI  - Improving a workstation in an existing cab by means of a participatory approach:
      the case of subway operators' workstations.
AB  - A study was conducted to identify possible solutions for redesigning a subway cab
      in order to improve the posture of drivers working in a restricted space. The
      approach used included the participation of a working group comprised of
      operations, maintenance, and engineering managers as well as several drivers.
      After 6 meetings in which different simulation techniques were used, the working
      group proposed changes for increasing the available space inside the cab and
      three seat designs. The involvement of the actors from the three departments
      affected by the changes, as well as the operators, throughout the process, was a
      determining factor in the advancement and acceptance of the projects. The fact
      that 400 cars are currently in service and must be modified means that it will
      take several years to implement the modifications in the entire fleet.

PMID- 19759435
TI  - Truck drivers hours-of-service regulations and occupational health.
AB  - Major industrialised countries, like the United States, Canada, Australia and
      countries of the European Union (EU) have Hours-of-Service (HoS) regulations for
      truck drivers that stipulate duration of continuous driving and rest periods. The
      purported aim is the improvement of road safety by reducing fatigue and
      drowsiness, but the regulations can also have a strong impact on the working
      conditions for drivers. Better working conditions for truck drivers is one of the
      aims of the EU HoS regulations, but they do not seem to fully produce the desired
      benefits. Truck drivers continue to have a high prevalence of back disorders,
      which have been linked with the time spent driving. They also have a high
      incidence of heart disease, which might be due to stress factors at work. Stress
      levels can be affected by HoS regulations, that leave the driver little job
      control and lead to social isolation. HoS regulations could contribute more to
      the improvement of working conditions of truck drivers through counteracting
      irregular work schedules, night driving and social isolation. Moving the focus
      from simple control of time spent driving or not driving to fatigue management
      could improve job control and working conditions for truck drivers without loss
      of traffic safety.

PMID- 19759436
TI  - Coping with chronic pain: current advances and practical information for
      clinicians.
AB  - Transferring knowledge and evidence from the pain psychology literature to all
      types of practitioners is one small but important step towards reducing the
      economic and personal cost of injuries. Through early identification of at-risk
      clients, it may be possible to prevent chronic pain from developing. Pain is a
      perception which is affected by physical, psychological and social factors, yet
      many health care professionals are only beginning to consider the relative
      contributions of each of these elements. It is essential that clinicians
      understanding of how a client's pain coping strategies impact progress and
      functional outcomes. For clients endorsing maladaptive methods of coping, one
      step is to refer the client to a psychologist; however, understanding of key
      underlying principles can also inform any type of treatment. All care providers
      involved with the client should discourage maladaptive strategies where
      appropriate and encouraging adaptive ones. Of equal importance is knowing whether
      or not the client is ready to adapt to change. Clinician knowledge of coping
      strategies and readiness may also help reduce the likelihood of clients
      withdrawing from treatment in frustration. The end result will hopefully be less
      disability and improved functioning of clients experiencing chronic pain.

PMID- 19759437
TI  - Narrative reflections on occupational transitions.

PMID- 19759438
TI  - Simulation study with minimised additional data requirements to analyse control
      and operation of WWTP Dorsten, Germany.
AB  - This paper describes a method to decrease the additional measurement effort
      during a model calibration/verification to create reliable models for plant
      optimisation. The method is based on the deterministic processes creating the dry
      weather inflow to municipal treatment plants, which can be described by a simple
      influent composition model. This method was applied to two wastewater treatment
      plants of Lippeverband and the usability is indicated by the good correlation
      between routine online effluent measurements and simulation results. This paper
      presents one of these applications, the case study WWTP Dorsten. The resulting
      model is used to analyse the current plant performance, to analyse bottlenecks
      and to develop future improvements of operation and control of this plant. A
      selection of control options is demonstrated.

PMID- 19759439
TI  - Foam formation on an Austrian-Hungarian lowland river: reasons, methods and
      solutions.
AB  - The occurrence of foam in a lowland river in Austria and shortly after the border
      with Hungary and the consequent protests from Hungarian inhabitants led to
      investigations concerning the reasons for foam formation. The aims of the study
      were (i) to specify objectively the scale of appearing of foam, (ii) to evaluate
      reasons for foam formation, and (iii) to develop abatement measures.

PMID- 19759440
TI  - Acquiring reproducible fluorescence spectra of dissolved organic matter at very
      low concentrations.
AB  - A method that would allow for fast and reliable measurements of dissolved organic
      matter (DOM), both at low and high concentration levels would be a valuable tool
      for online monitoring of DOM. This could have applications in a variety of areas
      including membrane treatment systems for drinking water applications which is of
      interest to our group. In this study, the feasibility of using fluorescence
      spectroscopy for monitoring DOM at very low concentration levels was demonstrated
      with an emphasis on optimizing the instrument parameters necessary to obtain
      reproducible fluorescence signals. Signals were acquired using a cuvette or a
      fibre optic probe assembly, the latter which may have applications for on-line or
      in-line monitoring. The instrument parameters such as photomultiplier tube (PMT)
      voltage, scanning rate and slit width were studied in detail to find the optimum
      parameter settings required. The results showed that larger excitation and
      emission slit widths were preferred, over larger PMT voltage or lower scanning
      rates, to obtain reproducible and rapid measurements when measuring very low
      concentration levels of DOM. However, this approach should be implemented with
      caution to avoid any reduction of the signal resolution.

PMID- 19759441
TI  - Nitrite formation during low pressure ultraviolet lamp irradiation of nitrate.
AB  - During ultraviolet light (UV) disinfection, nitrate (NO3-) present in raw water
      may transform to nitrite (NO2-) that can cause serious human diseases. In this
      study, the formation of NO2- from NO3- was studied at different experimental
      conditions under the irradiation of a low-pressure ultraviolet (LPUV) lamp at
      253.9 nm. The investigated experimental variables included initial NO3-
      concentration, solution pH (6.2-9.5), and hydrogen peroxide (H2O2) dose (0-25 mg
      L(-1)). Moreover, the effect of titanium dioxide (TiO2) was determined. Results
      showed that the formation of NO2- was enhanced at a high initial NO3-
      concentration and a high pH, but was inhibited, to some different degrees, by
      introduction of H2O2 or photocatalyst TiO2. The effect of pH on NO2- formation
      was probably due to the impact of hydrogen ion on the stability of several
      intermediates such as peroxynitrite (ONOO-), N2O3, and N2O4. And the inhibiting
      effects of H2O2 and TiO2 were attributable to production of additional hydroxyl
      radical (OH) that scavenged NO2-. At pH 9.5 and an initial NO3- concentration of
      10 mg L(-1) NO3--N, the concentration of NO2- produced was above 0.1 mg L(-1) NO2
      -N, the Germany drinking water standard. When 25 mg L(-1) H2O2 was added, the NO2
      level was decreased below the standard.

PMID- 19759442
TI  - Bioaugmentation to degrade the organic de-icers acetate and monopropylene glycol
      at low temperatures.
AB  - Two de-icers, potassium acetate and monopropylene glycol (MPG), used widespread
      as a runway and wing de-icer respectively, can exert high BOD in the surrounding
      waters. A bioaugmentation approach to degrade these de-icer compounds in the
      drainage water prior to discharge has been tested. A microbial consortium
      originating from soil was enriched at low temperatures (4 degrees C) in order to
      adapt to wintertime conditions. With 0.05 g CDW/L of biocatalyst, maximum
      specific removal rates up to 1.46 and 3.33 g acetate/g CDW d at 4 degrees C were
      achieved with and without biostimulation respectively. An acetate:MPG mixture of
      1:3 at a total COD concentration of 0.80 and 1.20 g/L was degraded in 12 days by
      83 and 70% respectively. Bioaugmentation in the field over a period of 25 days
      showed a removal of 88% MPG compared to 46% in the control. These results
      demonstrate that bioaugmentation of airport runoff water can be successfully
      applied to prevent organic de-icer compounds from entering the receiving surface
      waters.

PMID- 19759443
TI  - Evaluation of microbial fuel cell coupled with aeration chamber and bio-cathode
      for organic matter and nitrogen removal from synthetic domestic wastewater.
AB  - For simultaneous carbon and nitrogen removal via single stream, a microbial fuel
      cell (MFC) coupled with an aeration chamber and a bio-cathode was investigated.
      Without catalysts and any additional buffer, the MFC produced electricity
      continuously and the power density reached 1.3 W/m3 at a loading rate of 1.6 kg
      COD/m3 d. Simultaneously, the COD and the nitrate removal rate were 1.4 kg COD/m3
      d and 67 g NO3-N/m3 d, respectively. When the hydraulic retention time was
      changed from 6 to 0.75 hours, the power density significantly increased from 0.2
      to 10.8 W/m3 due to an increase of cathodic potential. When the aeration chamber
      was removed and the nitrate was injected into the cathode, the power density
      increased to 3.7 W/m3. At a high recirculation rate of 10 ml/min, the power
      density and the nitrate removal rate greatly increased to 34 W/m3 and 294 g NO3-
      N/m3 d, respectively.

PMID- 19759444
TI  - Methylene blue removal from contaminated waters using O3, natural zeolite, and
      O3/zeolite.
AB  - This paper compares experimental results on methylene blue (MB) removal systems
      based on ozone oxidation, zeolite adsorption, and simultaneous adsorption
      oxidation using ozone in the presence of natural zeolite. The effect of pH (2-8),
      and the presence of radical scavengers (sodium acetate) on process rates and
      removal efficiencies are assessed at laboratory scale. The experimental system
      consisted of a 1 L differential circular flow reactor and an ozone generator
      rated at 5 g O3/h. Results show that ozone oxidation combined with zeolite
      adsorption increases the overall MB oxidation rate with respect to ozonation
      process and zeolite adsorption. In presence of free radical scavenger, only a 25%
      of reduction on MB removal rate are observed in the simultaneous treatment, as
      compared with 70% when ozonation treatment is used, suggesting that MB oxidation
      reactions take mainly place on the zeolite surface.

PMID- 19759445
TI  - Heavy metals in a constructed wetland treating industrial wastewater:
      distribution in the sediment and rhizome tissue.
AB  - This study assessed copper and zinc distribution in the surface layer of sediment
      and rhizome tissue within the saturated surface vertical flow constructed wetland
      of CSBP Ltd, a fertiliser and chemical manufacturer located in Western Australia.
      Sediment and Schoenoplectus validus rhizome samples were collected at various
      distances from the inlet pipe while water samples are routinely collected. Water
      samples were analysed for nutrients and metals, sediments were analysed for total
      and bioavailable metals and rhizomes were analysed for total metals only. Mean
      influent copper and zinc concentrations were 0.19 mg/L and 0.24 mg/L
      respectively. The distribution of bioavailable Cu and Zn in the top sediment
      layer follows a horizontal profile. Analysis of variance (ANOVA) showed that the
      bioavailable fraction of these metals in sediments near the inlet pipe (30.2
      mg/kg Cu and 60.4 mg/kg Zn) is significantly higher than in sediments at the
      farthest location (10.3 mg/kg Cu and 26.1 mg/kg Zn). The average total Cu
      concentration in the sediment at the 2 m location has reached the 65 mg/kg
      trigger value suggested by the Interim Sediment Quality Guidelines (ANZEEC 2000).
      Cu and Zn concentrations in the rhizome of S. validus do not vary significantly
      among different locations. Whether Cu and Zn concentrations at the CSBP wetland
      may reach toxic levels to plants and bacteria is still unknown and further
      research is required to address this issue. The surface component of the wetland
      favours sedimentation and binding of metals to the organic matter on the top of
      the sediment, furthermore, the sediment which tends to be anoxic with reducing
      conditions acts as a sink for metals.

PMID- 19759446
TI  - Drinking water from alternative water sources: differences in beliefs, social
      norms and factors of perceived behavioural control across eight Australian
      locations.
AB  - Australia is facing serious challenges in the management of water in various
      urban and regional locations. Two popular responses to these challenges are
      increasing supply through alternative water sources such as recycled and
      desalinated water. However, significant gaps exist in our knowledge of community
      attitudes to these alternative sources of water, particularly for potable use.
      This paper reports results from an Australian study of community attitudes to
      alternative water sources. Sixty six qualitative interviews were held at eight
      locations with distinctly different water situations. This paper explores all
      three antecedents to the behaviour of drinking recycled water and desalinated
      water as postulated by the Theory of Planned Behaviour: attitudes, social norms
      and factors of perceived behavioural control. Key results indicate that while
      people hold both positive and negative beliefs (mostly cost, health and
      environmental concerns) about water from alternative sources, nearly all of them
      are willing to drink it if the water crisis were to deteriorate further. People
      also feel they lack knowledge and state that information from scientists would
      influence their decision to drink recycled and desalinated water most. Friends
      and relatives are most influential in preventing people from drinking recycled
      water. The findings reported in this paper have major implications for water
      policy, and will be of particular interest to water engineers. The paper raises a
      provocative question: Is it better to avoid public consultation in introducing
      water from alternative sources?

PMID- 19759447
TI  - Disintegration of sewage sludge with bifrequency ultrasonic treatment.
AB  - A bifrequency ultrasonic generating trough was used to improve disintegration of
      sewage sludge from thickener tanks. Ultrasonic operating parameters such as
      frequency, power, and time were optimized. Ultrasonic treatment successfully
      disintegrated the floc structure of sewage sludge and promoted the release of
      organic matter and metal ions such as Ca2+ and Mg2+. After ultrasonic treatment,
      soluble chemical oxygen demand (SCOD) in the sludge solution increased 11.28
      49.06%, while the concentrations of Ca2+ and Mg2+ rose 5.5-25.0% and 2.7-19.0%,
      respectively. The ultrasonic frequency of 25 kHz was most effective in
      disintegrating sludge, and high energy densities and longer treatment time
      increased SCOD and metal ion release. The optimal parameters that promoted the
      increase SCOD were 25 kHz, 75 W/L and 60 s. Under these conditions, double
      frequency ultrasonication was more effective than single-frequency
      ultrasonication.

PMID- 19759448
TI  - Application of particle-size analysis in coagulation/flocculation for reclamation
      of a secondary effluent.
AB  - Reclaimed secondary effluent is an important alternative water resource for urban
      areas; the particle-size distribution approach was applied in this study for
      purpose of screening and evaluating treatment processes for reclamation of a
      secondary effluent. Two particle-size analysing technologies namely (1) the laser
      light scattering technology and (2) the sequential membrane filtration technology
      were used in this study; particulate characteristics of the secondary effluent,
      of the reclaimed water by coagulation and of the reclaimed water by combined
      coagulation/flocculation were investigated. Optimisation of coagulation and/or
      combined coagulation/flocculation technologies were carried out with the help of
      particulate analysis of priority pollutants, following which studies on turbidity
      removing mechanisms of both processes were discussed. Comparison studies
      indicated that increase of turbidity removal efficiency by flocculation happened
      mainly in the particulate range of 0.2-0.3 microm and 5-8 microm; flocculation
      did not help or even slightly deteriorated turbidity removal of particles whose
      sizes are smaller than 0.2 microm and/or in the range of 0.3-5 microm.

PMID- 19759449
TI  - Re-thinking wastewater landscapes: combining innovative strategies to address
      tomorrow's urban wastewater treatment challenges.
AB  - Most major cities worldwide face urban water management challenges relating to
      drinking supply, stormwater and wastewater treatment, and ecological
      preservation. In light of climate change and finite natural resources, addressing
      these challenges in sustainable ways will require innovative solutions arising
      from interdisciplinary collaboration. This article summarizes five major urban
      water management strategies that bridge the fields of engineering, ecology,
      landscape architecture, and urban planning. A conceptual implementation of these
      strategies is demonstrated through a design for a small constructed wetland
      treatment system in San Francisco, California. The proposed decentralized system
      described in this article consists of a detention basin, vegetated and open free
      water surface wetlands, and ultraviolet disinfection. In wet weather, the system
      would detain and treat combined sewer discharges (CSD), and in dry weather it
      would treat residential greywater for toilet flushing and irrigation in a nearby
      neighborhood. It is designed to adapt over time to changing climatic conditions
      and treatment demands. Importantly, this proposal demonstrates how constructed
      wetland engineers can incorporate multiple benefits into their systems, offering
      a vision of how wastewater infrastructure can be an attractive community,
      educational, recreational, and habitat amenity through the integration of
      engineering, ecology, and landscape design.

PMID- 19759450
TI  - Modelling of COD removal in a biological wastewater treatment plant using
      adaptive neuro-fuzzy inference system and artificial neural network.
AB  - This work evaluated artificial neural network (ANN) and adaptive neuro-fuzzy
      inference system (ANFIS) modelling methods to estimate organic carbon removal
      using the correlation among the past information of influent and effluent
      parameters in a full-scale aerobic biological wastewater treatment plant. Model
      development focused on providing an adaptive, useful, practical and alternative
      methodology for modelling of organic carbon removal. For both models, measured
      and predicted effluent COD concentrations were strongly correlated with
      determination coefficients over 0.96. The errors associated with the prediction
      of effluent COD by the ANFIS modelling appeared to be within the error range of
      analytical measurements. The results overall indicated that the ANFIS modelling
      approach may be suitable to describe the relationship between wastewater quality
      parameters and may have application potential for performance prediction and
      control of aerobic biological processes in wastewater treatment plants.

PMID- 19759451
TI  - Arsenic removal by iron oxide coated sponge: treatment and waste management.
AB  - One of the problems in drinking water that raises concern over the world is that
      millions of people still have to use arsenic-contaminated water. There is a
      worldwide need to develop appropriate technologies to remove arsenic from water
      for household and community water supply systems. In this study, a new material
      namely iron oxide coated sponge (IOCSp) was developed and used to remove arsenic
      (As) from contaminated groundwater in Vietnam. The results indicated that IOCSp
      has a high capacity in removing both As (V) and As (III). The adsorption capacity
      of IOCSp was up to 4.6 mg As/g IOCSp, showing better than many other materials.
      It was observed from a pilot study that a small quantity of IOCSp (180 g) could
      reduce As concentration of 480 microg/L in 1.5 m3 of contaminated natural water
      to below 40 microg/L. In addition, an exhausted IOCSp, containing a large amount
      of arsenic (up to 0.42 wt %) could safely be disposed through the
      solidification/stabilization with cement. Addition of fly ash also reduced the
      amount of arsenic in the leachate.

PMID- 19759452
TI  - Effectiveness of ozonation and chlorination on municipal wastewater treatment
      evaluated by a battery of bioassays and biomarkers.
AB  - A battery of bioassays, including biological toxicity as well as in vitro mouse
      spleen lymphoproliferative responses and cytokine production, was conducted to
      compare the effectiveness of tertiary treatment methods such as coagulation
      (Coag) and absorption on granular activated carbon (GAC) and disinfection
      processes such as chlorination and ozonation in removing toxic or stress inducing
      agents from reclaimed wastewater. Whole effluent toxicity (WET) testing of
      secondary treated (ST) wastewater using as test species Vibrio fischeri, Daphnia
      magna and Tetrahymena thermophila as well as phytotoxicity revealed moderate
      toxicity effects that depend on the organism used. All bioassays exhibited
      decrease of the ecotoxicological responses after tertiary treatment. However,
      mitogenic responses were proved to be more sensitive. Endotoxin present in ST
      samples may be responsible for the increased strong lymphoproliferative activity
      as well as interleukin-1 (IL-1) production by mouse splenocytes. Tertiary
      treatment of ST with coagulation and/or adsorption on granular activated carbon
      (GAC) in combination with ozonation reduced WET to control levels. Ozonation
      alone or in combination with any other treatment removed endotoxin more
      efficiently than chlorination and thus reduced spleen lymphoproliferative
      responses and IL-1 production.

PMID- 19759453
TI  - Hydrological modeling in alpine catchments: sensing the critical parameters
      towards an efficient model calibration.
AB  - For the Tyrolean part of the river Inn, a hybrid model for flood forecast has
      been set up and is currently in its test phase. The system is a hybrid system
      which comprises of a hydraulic 1D model for the river Inn, and the hydrological
      models HQsim (Rainfall-runoff-discharge model) and the snow and ice melt model
      SES for modeling the rainfall runoff form non-glaciated and glaciated tributary
      catchment respectively. Within this paper the focus is put on the hydrological
      modeling of the totally 49 connected non-glaciated catchments realized with the
      software HQsim. In the course of model calibration, the identification of the
      most sensitive parameters is important aiming at an efficient calibration
      procedure. The indicators used for explaining the parameter sensitivities were
      chosen specifically for the purpose of flood forecasting. Finally five model
      parameters could be identified as being sensitive for model calibration when
      aiming for a well calibrated model for flood conditions. In addition two
      parameters were identified which are sensitive in situations where the snow line
      plays an important role.

PMID- 19759454
TI  - Comparison of biological activated carbon (BAC) and membrane bioreactor (MBR) for
      pollutants removal in drinking water treatment.
AB  - Biological activated carbon (BAC) and membrane bioreactor (MBR) were
      systematically compared for the drinking water treatment from slightly polluted
      raw water under the same hydraulic retention time (HRT) of 0.5 h. MBR exhibited
      excellent turbidity removal capacity due to the separation of the membrane; while
      only 60% of influent turbidity was intercepted by BAC. Perfect nitrification was
      achieved by MBR with the 89% reduction in ammonia; by contrast, BAC only
      eliminated a moderate amount of influent ammonia (by 54.5%). However, BAC was
      able to remove more dissolved organic matter (DOM, especially for organic
      molecules of 3,000 approximately 500 Daltons) and corresponding disinfection by
      product formation potential (DBPFP) in raw water than MBR. Unfortunately,
      particulate organic matter (POM) was detected in the BAC effluent. On the other
      hand, BAC and MBR displayed essentially the same capacity for biodegradable
      organic matter (BOM) removal. Fractionation of DOM showed that the removal
      efficiencies of hydrophobic neutrals, hydrophobic acids, weakly hydrophobic acids
      and hydrophilic organic matter through BAC treatment were 11.7%, 8.8%, 13.9% and
      4.8% higher than that through MBR; while MBR achieved 13.8% higher hydrophobic
      bases removal as compared with BAC.

PMID- 19759455
TI  - Ultrasound pre-treatment for anaerobic digestion improvement.
AB  - Prior research indicates that ultrasounds can be used in batch reactors as pre
      treatment before anaerobic digestion, but the specific energy required at
      laboratory-scale is too high. This work evaluates both the continuous ultrasound
      device performance (efficiency and solubilisation) and the operation of anaerobic
      digesters continuously fed with sonicated sludge, and presents energy balance
      considerations. The results of sludge solubilisation after the sonication
      treatment indicate that, applying identical specific energy, it is better to
      increase the power than the residence time. Working with secondary sludge, batch
      biodegradability tests show that by applying 30 kWh/m3 of sludge, it is possible
      to increase biogas production by 42%. Data from continuous pilot-scale anaerobic
      reactors (V=100 L) indicate that operating with a conventional HRT=20 d, a
      reactor fed with pre-treated sludge increases the volatile solids removal and the
      biogas production by 25 and 37% respectively. Operating with HRT=15 d, the
      removal efficiency is similar to the obtained with a reactor fed with non
      hydrolysed sludge at HTR=20 d, although the specific biogas productivity per
      volume of reactor is higher for the pretreated sludge. Regarding the energy
      balance, although for laboratory-scale devices it is negative, full-scale
      suppliers state a net generation of 3-10 kW per kW of energy used.

PMID- 19759456
TI  - Contamination, bioaccumulation and toxic effects of perfluorinated chemicals
      (PFCs) in the water environment: a review paper.
AB  - Perfluorinated compounds such as perfluorooctane sulfonate (PFOS) and
      perfluorooctane acid (PFOA) have been recognized as emerging environmental
      pollutants because of their ubiquitous occurrence in the environment, biota and
      humans. The paper focuses on the distribution, bioaccumulation and toxic effects
      of PFOS and PFOA in the water. From the available literature, tap and surface
      water samples in several countries were found to be contaminated with PFOS and
      PFOA. These compounds were detected globally in the tissues of fish, bird and
      marine mammals. Their concentrations from relatively more industrialized areas
      were greater than those from the less populated and remote locations. Blood
      samples of occupationally exposed people and the general population in various
      countries were found to contain PFOS and PFOA which suggested a possibility of
      atmospheric transport of these compounds. There is still a death of information
      about the environmental pathways of PFOS and PFOA. The presence of these
      compounds in the tap water, surface water and animal and human tissues indicates
      their global contamination and bioaccumulative phenomena in the ecosystems.

PMID- 19759457
TI  - Impact of input data uncertainties on urban stormwater model parameters.
AB  - The use of urban drainage models requires careful calibration, where model
      parameters are selected in order to minimize the difference between measured and
      simulated results. It has been recognized that often more than one set of
      calibration parameters can achieve similar model accuracy. A probability
      distribution of model parameters should therefore be constructed to examine the
      model's sensitivity to its parameters. With increasing complexity of models, it
      also becomes important to analyze the model parameter sensitivity while taking
      into account uncertainties in input and calibration data. In this study a
      Bayesian approach was used to develop a framework for quantification of impacts
      of uncertainties in the model inputs on the parameters of a simple integrated
      stormwater model for calculating runoff, total suspended solids and total
      nitrogen loads. The framework was applied to two catchments in Australia. It was
      found that only systematic rainfall errors have a significant impact on flow
      model parameters. The most sensitive flow parameter was the effective impervious
      area, which can be calibrated to completely compensate for the input data
      uncertainties. The pollution model parameters were influenced by both systematic
      and random rainfall errors. Additionally an impact of circumstances (e.g.
      catchment type, data availability) has been recognized.

PMID- 19759458
TI  - A case independent approach on the impact of climate change effects on combined
      sewer system performance.
AB  - Design and construction of urban drainage systems has to be done in a predictive
      way, as the average lifespan of such investments is several decades. The design
      engineer has to predict many influencing factors and scenarios for future
      development of a system (e.g. change in land use, population, water consumption
      and infiltration measures). Furthermore, climate change can cause increased rain
      intensities which leads to an additional impact on drainage systems. In this
      paper we compare the behaviour of different performance indicators of combined
      sewer systems when taking into account long-term environmental change effects
      (change in rainfall characteristics, change in impervious area and change in dry
      weather flow). By using 250 virtual case studies this approach is--in principle-
      a Monte Carlo Simulation in which not only parameter values are varied but the
      entire system structure and layout is changed in each run. Hence, results are
      more general and case-independent. For example the consideration of an increase
      of rainfall intensities by 20% has the same effect as an increase of impervious
      area of +40%. Such an increase of rainfall intensities could be compensated by
      infiltration measures in current systems which lead to a reduction of impervious
      area by 30%.

PMID- 19759459
TI  - A constructed wetland model for synthetic reactive dye wastewater treatment by
      narrow-leaved cattails (Typha angustifolia Linn.).
AB  - Textile wastewater is contaminated by reactive dye causing unattractive levels of
      wastewater color, high pH and high salt content when discharged into public water
      systems. Decolorization of textile wastewater by plant, phytoremediation, is an
      alternative, sustainable method which is suitable for long term operation. Narrow
      leaved cattails are one species of wetland plant with efficiency for decolorizing
      and remediating textile wastewater. In addition, chemical oxygen demand (COD) can
      be lowered and dye residue can be removed. The plant also showed a good salt
      tolerance even after being exposed to a salt solution for 15 days. The narrow
      leaved cattails were set up in a constructed wetland model with a vertical flow
      system operating from bottom to top for synthetic reactive dye wastewater (SRDW)
      removal. Narrow-leaved cattails could achieve the removal of SRDW at
      approximately 0.8 g(SRDW) m(-2) day(-1). Decolorization of SRDW by this plant was
      approximately 60%. The advantage of this method is that it is suitable for
      textile wastewater management and improvement of wetland. These plants could
      lower COD, remove dye, sodium and total dissolved solids (TDS) whereas other
      biological and chemical methods could not remove TDS and dye in the same time.
      These results suggested that the spongy cell structure of this plant has the
      ability to absorb large amounts of water and nutrients. Physico-chemical analysis
      revealed increasing amounts of sulfur, silicon, iron and calcium in the plant
      leafs and roots after exposure to wastewater. Proteins or amide groups in the
      plant might help in textile dye removal. Regarding decolorization, this plant
      accumulates dye in the intercellular space and still grows in this SRDW
      condition. Hence, it can be noted here that narrow-leaved cattails are efficient
      for textile dye wastewater treatment.

PMID- 19759460
TI  - Road runoff management using over-the-shoulder infiltration: real-scale
      experimentation.
AB  - A new management policy regarding road runoff was proposed in 2002 by the Swiss
      Federal Office for the Environment (FOEN). This new concept is based on the
      diffuse infiltration of road runoff into embankment slopes, where soils will
      filter particles and contaminants. The shoulder lying between road surface and
      infiltration slopes must be impervious in order to maximise the amount of water
      reaching the slope and avoid losses in the road structure. The implementation of
      this new concept should lower the impact of roads on the environment, improve
      aquifer recharge and reduce construction costs. The Swiss Federal Road Office
      (FedRO) decided to carry out real-scale investigations regarding this new policy
      and thus commissioned the GEOLEP to design, build, and test 5 different shoulder
      structures. This paper presents the results of a 2-years survey of infiltration
      processes in these shoulders to establish the best performing structure. The
      first three shoulders were overlaid with 5 cm of gravel mixed with humus, gravel
      mixed with clay, and seeded with lawn, respectively. The latter two had
      impervious layers located 26 cm deep: the road bituminous basement (road base)
      was prolonged and coated with bitumen in the first case, and a sodic-bentonite
      geotextile was used in the second. Both were covered with gravel. All shoulders
      were equipped with basal collecting devices that measured hydraulic fluxes
      seeping through the shoulders. In total, 112 natural precipitations and 3
      artificial events were monitored. Artificial events mimicked known transitory
      regimes (thunderstorms) or were performed with constant regime. The goal was to
      effectively assess infiltration processes in shoulders. Results showed that
      shoulders made of gravel and humus or lawn were highly ineffective (only 30 to
      40% of runoff is conducted to the infiltration slope). Gravel and clay was more
      efficient with a proportion of approximately 60%. The shoulder with prolonged
      road base showed similar results since the bituminous coating was in fact rather
      permeable. The best results were exhibited by the shoulder waterproofed with
      bentonitic geotextile, which allowed no water to penetrate. This material already
      proved to be very powerful in groundwater catchments. The authors thus proposed a
      combination of sodic-bentonite geotextile covered by a gravel and clay mixture.
      This would be the most efficient shoulder: it will convey all the runoff to
      infiltration slopes, thereby optimising its filtration, which in turn will
      enhance environmental conditions in the vicinity of roads.

PMID- 19759461
TI  - Visible light assisted photocatalytic degradation of acid red 88 using Au-ZnO
      nanophotocatalysts.
AB  - Photocatalytic degradation of acid red 88 (AR88) in aqueous suspensions of Au-ZnO
      nanoparticles under visible light illumination was studied in order to evaluate
      various effects of the Au deposition on the ZnO photocatalytic activity. Au-ZnO
      nanoparticles were prepared by deposition precipitation method and characterized
      by different analytical techniques. In Au-ZnO system, all gold nanoparticles were
      tethered on the surface of zinc oxide particles. This enhanced the AR88
      adsorption on the Au-ZnO surface and acted as electron traps which is the main
      reason for significant enhancement in the AR88 photodegradation under visible
      light illumination compared to ZnO alone. Further in the presence of electron
      acceptors complete decolorization of the dye was observed, which might be due to
      immediate trapping of the photogenerated electrons by electron acceptors.

PMID- 19759462
TI  - Transformation of nitrogen and distribution of nitrogen-related bacteria in a
      polluted urban stream.
AB  - Most researchers focused on either nitrogen species or microbial community for
      polluted urban stream while ignoring the interaction between them and its effect
      on nitrogen transformation, which restricted the rational selection of an
      effective and feasible remediation technology. Taking Buji stream in Shenzhen
      (China) as target stream, the distribution of nitrogen-related bacteria was
      investigated by most probable number (MPN) besides analysis of nitrogen species
      etc. The nitrogen-related bacteria in sediment were 10(2) times richer than those
      in water. Owing to their faster growth, the MPN of ammonifying bacteria and
      denitrifying bacteria were 10(5) and 10(2) times higher than those of nitrifying
      bacteria, respectively. The ammonifying bacteria numbers were significantly
      related to BOD5 in water, while nitrifying bacteria in sediment correlated well
      with nitrate in water. Thus, nitrification occurred mainly in sediment surface
      and was limited by low proportion of nitrifying bacteria. The denitrifying
      bacteria in sediment had good relationship with BOD5 and nitrite and nitrate in
      water. Low DO and rich organic compounds were beneficial to denitrification but
      unfavourable to nitrification. Denitrification was restricted by low nitrite and
      nitrate concentration. These results could be served as a reference for
      implementing the remediation scheme of nitrogen polluted urban stream.

PMID- 19759463
TI  - Removal of endocrine disrupting chemicals from aqueous phase using spherical
      microporous carbon prepared from waste polymeric exchanger.
AB  - A spherical microporous carbon adsorbent (CR-1), which was developed by
      carbonization and activation of the waste polysulfonated cation-exchanger, was
      used to remove Dimethyl phthalate (DMP) and 2, 4-dichlorophenol (2, 4-DCP) as the
      model compounds of EDCs from the aqueous solution. Four adsorption isotherm
      models, Langmuir, Freundlich, Toth and Polanyi-Dubinin-Manes equations were
      tested to correlate the experimental data, Toth and Polanyi-Dubinin-Manes
      isotherms models provided the best correlation. The Henry's law constants
      calculated from Toth equation were found to be 705.957 and 6,724.713 L g(-1) for
      2, 4-DCP and DMP at 298 K, respectively, and the larger exponents n of the
      Freundlich model were 9.011 and 9.93 for 2, 4-DCP and DMP at 298 K, respectively.
      The values of Henry's law constants and exponent n of the Freundlich suggested
      that CR-1 was an effective adsorbent for removal of low concentrations of DMP and
      2, 4-DCP from aqueous solution. Moreover, the adsorption kinetics results showed
      that adsorption of 2, 4-DCP and DMP on CR-1 was a pseudo-second-order process
      controlled by intra-particle diffusion and that adsorption uptake reached quickly
      half of equilibrium capacities within 20 min.

PMID- 19759464
TI  - Influence of sample preservation on endotoxin measurement in water.
AB  - Appropriate preservation of a range of water types prior to analysis for
      endotoxin was investigated, including sample storage and addition of sodium
      thiosulphate. Biologically active endotoxin in water samples was assayed using a
      chromogenic Limulus Amoebocyte Lysate (LAL) assay. Statistical analysis of
      measured mean endotoxin levels obtained for samples with and without sodium
      thiosulphate showed no significant difference in results. There was a 44% mean
      decline in the concentration of detectable endotoxin in water samples stored at 
      80 degrees C for 4 weeks compared with samples stored at 4 degrees C and analysed
      within 24 hours. Freezing of water samples at -80 degrees C in pyrogen-free
      containers for 4 weeks or longer, then thawing may lead to considerable endotoxin
      loss; however the addition of sodium thiosulphate to water samples interferes
      minimally with the LAL assay. These results provide methodological information
      that can be used to assist researchers in future water endotoxin monitoring
      studies. The validation and standardisation of water sample preservation
      protocols are necessary, given the likely increase in the quantification of
      endotoxin levels in a variety of water sources and the use of such results for
      health effect determinations.

PMID- 19759465
TI  - Vulnerability of water services in Pacific Island Countries: combining
      methodologies and judgment.
AB  - Water services in Pacific Island Countries are particularly vulnerable due to a
      range of circumstances such as the scale of operation, remoteness of location,
      financial constraints, cultural complexity and the ability to access technical
      and other capacity by their administrations. Additionally, the authors argue that
      comparative assessment of water needs for differing locations is fraught with
      difficulty because of the combination of systemic complexity, diversity of
      situations and lack of suitable, consistent and objective data. In these
      challenging situations, a method for assessment of the vulnerability of water
      services has been developed on the basis of knowledge and experiences of water
      professionals, elicited using a structured group interaction known as a Delphi
      survey. The Delphi survey has been undertaken with a range of stakeholders
      including panels of experts, funding agencies and local decision makers. Through
      the Delphi process, key factors contributing to vulnerability have been
      identified and the output has been used to develop an index methodology. Such an
      index methodology, similar to the Climate Vulnerability Index, has a number of
      dimensions, variables and appropriate weights expressed within a set of
      equations. Given quantification of variables, this method can be used to assess
      the relative vulnerability of water services in Pacific Island Countries. The
      method used to develop this index could also be applied to other contexts where
      appropriate.

PMID- 19759466
TI  - Nitrogen removal via nitrite in domestic wastewater treatment using combined salt
      inhibition and on-line process control.
AB  - Nitrogen removal through the nitrite pathway has been successfully achieved using
      on-line aeration length control. However, it takes a long time period to get
      steady performance when using on-line control as the sole strategy. On the other
      hand, salt inhibition has also been used to achieve the nitrite pathway, with
      potentially adverse effects on the overall microbial community at high salt
      concentrations. The objective of this study is to develop a control strategy
      based on the combination of low salt inhibition levels and on-line control to
      accelerate the achievement of nitrite pathway in a sequencing batch reactor (SBR)
      treating domestic wastewater. Salt concentrations and on-line control parameters
      were chosen in batch tests. The recovery of the nitrite-oxidizing bacteria (NOB)
      activity was examined after stopping on-line control and salt dosing. The
      findings clearly show that combining salt inhibition at low salinity (5 g/L) with
      on-line pH control is an efficient strategy to achieve nitrogen removal via
      nitrite quickly and steadily.

PMID- 19759467
TI  - Use of surrogate modelling for multiobjective optimisation of urban wastewater
      systems.
AB  - Simulation models are now available to represent the sewer network, wastewater
      treatment plant and receiving water as an integrated system. These models can be
      combined with optimisation methods to improve overall system performance through
      optimal control. Evolutionary algorithms (EAs) have been proven to be a powerful
      method in developing optimal control strategies; however, the intensive
      computational requirement of these methods imposes a limit on their application.
      This paper explores the potential of surrogate modelling in multiobjective
      optimisation of urban wastewater systems with a limited number of model
      simulations. A surrogate based method, ParEGO, is combined with an integrated
      urban wastewater model to solve real time control problems. This method is
      compared with the popular NSGA II, by using performance indicators: the
      hypervolume indicator, additive binary epsilon-indicator and attainment surface.
      Comparative results show that ParEGO is an efficient and effective method in
      deriving optimal control strategies for multiple objective control problems with
      a small number of simulations. It is suggested that ParEGO can greatly improve
      computational efficiency in the multiobjective optimisation process, particularly
      for complex urban wastewater systems.

PMID- 19759468
TI  - Possible link between the severe respiratory illness outbreak in Mexico and swine
      influenza in southwestern United States?
AB  - Reminiscent of the Severe Acquired Respiratory Syndrome (SARS) outbreak during
      the spring and fall of 2003, an outbreak of Severe Respiratory Illness (SRI) in
      Mexico has world health officials in a state of concern. The concern centers on
      the fact that as of April 24, 2009 over 134 cases have been reported in Mexico
      with an accompanying high mortality rate in healthy young adults. With new
      information surfacing from public health investigations of recent cases of swine
      influenza in the United States, here we discuss putative links between the
      outbreak of SRI in Mexico and the emergence of a novel swine influenza A (H1N1)
      strain in several southwestern U.S. states.

PMID- 19759469
TI  - Macrolides for the treatment of severe respiratory illness caused by novel H1N1
      swine influenza viral strains.

PMID- 19759470
TI  - Drug resistant Mycobacterium tuberculosis in Mexico.
AB  - Tuberculosis (TB) remains a serious public health problem, worsened by an
      increased frequency of multidrug-resistant (MDR) Mycobacterium tuberculosis
      strains. The World Health Organization (WHO) and the International Union Against
      Tuberculosis and Lung Disease (IUATLD) launched the Global Project on Anti
      Tuberculosis Drug Resistance Surveillance to measure the prevalence of drug
      resistance. Data from the global reports on resistance to anti-tuberculosis (anti
      TB) drugs have shown that drug resistance still presents worldwide and that MDR
      TB is present in almost all the world. Though the Global Project (WHO) has been
      operating since 1994, very few countries and states have reported new
      information. Data from repeated surveys employing comparable methodologies over
      several years are essential to determine with any certainty in which direction
      the prevalence of drug resistance is moving. Drug-resistant tuberculosis and MDR
      TB have been identified in Mexico, even with the existence of a National
      Tuberculosis Program based on Directly Observed Treatment, Short-course (DOTS).
      This review discusses available surveillance data on drug susceptibility data for
      TB in different states of Mexico.

PMID- 19759471
TI  - Enterotoxigenic coagulase positive Staphylococcus in milk and milk products, lben
      and jben, in northern Morocco.
AB  - BACKGROUND: The aim of this research was to determine the prevalence of
      enterotoxin genes (sea-seo) in Coagulase Positive Staphylococcus (CPS) isolated
      from unpasteurized milk and milk products. These results were compared with the
      results obtained by using the detection kit SET-RPLA for the specific detection
      of staphylococcal enterotoxins (SEA-SED). METHODOLOGY: Eighty-one samples of milk
      and milk products were analyzed for the presence of Staphylococcus strains. Forty
      six coagulase positive Staphylococcus isolates were tested for the production of
      staphylococcal enterotoxins (SEA-SED) by using the reversed passive latex
      agglutination method. The strains were also tested for the presence of se genes
      (sea-seo) by polymerase chain reaction. RESULTS: One or more classical
      enterotoxin products (SEA-SED) were observed in 39% of the strains tested, while
      se genes were detected in 56.5%. SEA and sea were most commonly detected. For
      newly discovered se genes among CPS isolates tested in this study, except the seh
      gene which was revealed in four isolates (8.7 %), none of the strains harbored
      any of the other se genes (see, seg, sei, sej, sek, sel, sem, seo and sen).
      CONCLUSIONS: The finding of a pathogen such as staphylococci-producing SEs and
      containing se genes in milk and milk products in northern Morocco may indicate a
      problem for public health in this region. The presence of enterotoxigenic strains
      in food does not always necessarily mean that the toxin will be produced. For
      that reason, the combination of both methods (RPLA and PCR) is a guarantee for
      success in diagnostic analysis tests.

PMID- 19759472
TI  - Extended spectrum AmpC and metallo-beta-lactamases in Serratia and Citrobacter
      spp. in a disc approximation assay.
AB  - OBJECTIVES: This study aimed to develop a novel model for detection of extended
      spectrum beta-lactamase (ESBL), AmpC and metallo-beta-lactamase (MBL) producing
      Serratia and Citrobacter species using cefoperazone sulbactam as well as other
      inducer-substrate combinations in a disc approximation assay. In the absence of
      molecular tools in developing countries, we attempted to standardize simple
      phenotypic techniques for detection of beta-lactamases to allow effective patient
      care in our countries. These techniques have been scarcely used in Serratia and
      Citrobacter spp., which are emerging as significant pathogens in our region.
      METHODOLOGY: Clinical isolates of Serratia and Citrobacter were tested for ESBL
      production. Cefoperazone (CP)/cefoperazone sulbactam (CPS), piperacillin
      (PIP)/piperacillin-tazobactam (TZP) and ceftazidime (CAZ)/ceftazidime-clavulanic
      acid (CAZ-CLAV) combinations were compared for their ability to detect ESBL
      producers phenotypically. Multi-drug resistant strains were further tested for
      detection of inducible/derepressed AmpC mutants by a disc approximation assay.
      Isolates were screened for MBL production by Imipenem (IMI). MBL production was
      confirmed using Ethylenediaminetetraacetic acid (EDTA) in a double disc synergy
      assay and Hodge test. Minimal inhibitory concentration (MIC) was performed for
      CP, CPS and IMI by agar dilution method for all isolates of Serratia and
      Citrobacter spp. RESULTS: Thirty-three percent of isolates of Serratia spp. and
      35.4% of Citrobacter spp. were ESBL producers. CPS was a more sensitive inducer
      of ESBL than TZP and CAZ/CAZ-CLAV. AmpC producers were detected in 25.6% of the
      isolates of Serratia spp. (40% inducible and 60% derepressed mutants) and in
      35.4% of the isolates of Citrobacter spp. (33% inducible and 66% derepressed
      mutants). Six isolates (four class B and two class A) of Serratia and eight
      isolates (seven class B and one class A) of Citrobacter spp. were MBL producers.
      Multiple mechanisms co-existed in eight isolates of Serratia and 15 isolates of
      Citrobacter spp. CPS was more effective in identifying ESBLs and inducible AmpC
      producers as well as type 1 carbapenemases than TZP and CAZ-CLAV were able to
      identify inducible AmpC producers. CONCLUSIONS: The high prevalence of ESBL,
      AmpC, and MBL in Serratia and Citrobacter species in this study suggests that
      detection of these by phenotypic methods in the absence of more specific
      molecular tests should be actively considered in not only developing countries
      but also in the developed world as this approach can lead to timely and
      appropriate antibiotic treatment. CPS may be advised due to the triple advantage
      of detection of all three types of beta-lactamases.

PMID- 19759473
TI  - Increasing prevalence of antimicrobial resistance among Enterobacteriaceae
      uropathogens in Bangui, Central African Republic.
AB  - BACKGROUND: Because of the previous high prevalence of resistance to usual
      antibiotics among uropathogens in Bangui, Central African Republic (CAR), a
      survey focused on Enterobacteriaceae, the most prevalent group responsible for
      urinary tract infections (UTIs), was conducted. The aim was to help health
      authorities revise antibiotic policies. METHODOLOGY: We performed a retrospective
      analysis of all cases of confirmed UTIs due to Enterobacteriaceae in outpatients
      attending the Institut Pasteur de Bangui (IPB), CAR, between 2004 and 2006.
      RESULTS: During the study period, 560 (10.9% of urine submissions) UTIs were
      confirmed and 443 Enterobacteriaceae strains were isolated, representing 79% of
      the causative agents for UTIs. Among these 560 strains, E. coli was the most
      common, representing 64% of the isolates, followed by K. pneumoniae (10%) and
      other Enterobacteriaceae (5%). Extended-spectrum beta-lactamase (ESBL) producing
      Enterobacteriaceae significantly increased from five (3.7%) to thirty-three
      (19.3%) between 2004 and 2006. A significantly increased resistance rate to
      nalidixic acid, ciprofloxacin and gentamicin was observed in ESBL-nonproducing
      Enterobacteriaceae over the study period. CONCLUSIONS: Empiric treatment for UTIs
      in Bangui should be reconsidered and prudent use of antibiotics, particularly
      ciprofloxacin, is highly recommended. The recent spread of ESBL-producing
      Enterobacteriaceae in central African outpatients is striking and underlines the
      need for further studies.

PMID- 19759474
TI  - Seroprevalence of antibodies against Chlamydia trachomatis inclusion membrane
      proteins B and C in infected symptomatic women.
AB  - BACKGROUND: Proteins in the inclusion membrane of Chlamydia trachomatis (CT) have
      been anticipated to play pivotal roles in the molecular and cellular interactions
      between the pathogen and host. However, there is lack of data on host immunity
      with respect to antibody responses against chlamydial inclusion proteins.
      METHODOLOGY: We used full-length fusion proteins for CT inclusion membrane
      proteins B and C (IncB and IncC respectively), two early-infection phase
      proteins, to study their role in antibody generation during human infection.
      RESULTS: Three hundred and fifty-five women (aged 22-36 years) attending the
      Gynaecology outpatient department, Safdarjang Hospital, New Delhi, India were
      enrolled in this hospital ethical committee approved study. Out of these, 108
      were diagnosed to be cervical CT-positive. Of these 108 patients, 67 (62.03%)
      showed ELISA positivity for IncB IgG, and 64 (59.25%) for IncC IgG. There was a
      positive correlation between antibody titres against IncB and IncC and with
      antibodies against CT major outer membrane protein (MOMP) in CT-positive sera.
      Our data also showed a positive association between antibody titres against IncB
      and IncC in patients with cervicitis and pelvic inflammatory disease (PID).
      Significantly high antibody titres were detected in cervicitis cases compared
      with PID. There were significantly higher levels of serum cytokines (TNF-alpha,
      IFN-gamma and IL-12) in Inc-positive cervicitis cases than in PID cases. In
      addition, our study also showed higher IncB and IncC IgG(2) titres in comparison
      to respective IgG1, IgG3 and IgG4 titres in CT-positive sera. CONCLUSION: Our
      data suggested that antibodies against CT IncB and IncC were prevalent in CT
      positive women diagnosed with cervicitis or PID.

PMID- 19759475
TI  - Clinico-pathological study of atypical pathogens in community-acquired pneumonia:
      a prospective study.
AB  - BACKGROUND: Atypical respiratory pathogens such as Mycoplasma pneumoniae,
      Legionella species, and Chlamydia pneumoniae are isolated with increasing
      frequency from community-acquired pneumonia (CAP). This study highlights the
      importance of organisms responsible for CAP. METHODOLOGY: One hundred consecutive
      patients with clinically and radiographically diagnosed CAP were evaluated from
      October 2005 to October 2006. Sputum, bronchoalveolar lavage, and blood samples
      were collected for microbiological culture. Determination was performed for
      specific immunoglobulin M (IgM) for Chlamydia pneumoniae, Mycoplasma pneumoniae,
      Legionella pneumophila, Coxiella burnettii, adenovirus, and influenza virus.
      RESULTS: The most common isolated bacteria was Streptococcus pneumoniae (22%)
      followed by Haemophilus influenzae (18%). Mycoplasma pneumoniae was isolated from
      5% and Legionella pneumophila was isolated from 5% of patients. The most common
      positive serological reaction was for Chlamydia pneumoniae (30%) and Adenovirus
      (30%). In the study of accuracy of determination of specific IgM for Mycoplasma
      pneumoniae and Legionella pneumophila compared to culture, the sensitivity was
      60% and 80% respectively, specificity was 93.7 %, and 98.9 % respectively, and
      accuracy was 92 % and 97 % respectively. CONCLUSION: This study highlights the
      prominence of mixed bacterial/viral infections in lower respiratory tract
      infection diagnosis. Our data showed that at least 30% of our patients had
      concurrent infections. This observation raises two important questions: 1)
      whether sequential or concurrent viral and bacterial infections have a
      synergistic impact on the evolution of disease in children; and 2) should
      diagnostic batteries for any patient with CAP include methods for detecting both
      the typical and atypical bacterial or viral pathogens.

PMID- 19759476
TI  - Escherichia coli shares T- and B-lymphocyte epitopes with Schistosoma mansoni.
AB  - BACKGROUND: In this study, we tested the cross-reaction between crude Escherichia
      coli antigen (ECA) and 3 crude Schistosoma mansoni antigens. METHODOLOGY: The
      schistosomal antigens used were cercarial antigen preparation (CAP), soluble worm
      antigen preparation (SWAP), and soluble egg antigen (SEA). Four groups each of 3
      mice received 2 intraperotineal immunizations with the above-mentioned antigens
      at a two-week interval. The dose of the ECA was 20 microg/100 microl PBS/mouse
      and that of any of the used schistosomal antigens was 50 microg/100 microl
      PBS/mouse. IgM and IgG reactivities and cross-reactivities were tested in
      individual immunized mice sera (IMS) against the above-mentioned antigens by
      ELISA and Western blotting. The changes in the B, CD4+ and CD8+ -T cells' counts
      post immunization were recorded. RESULTS: Priming with ECA caused significant
      increases in IgM (P<0.05) against CAP and SWAP, while both priming and boosting
      with ECA caused a significant elevation in the IgG only against SWAP. Priming and
      boosting with ECA or schistosomal antigens caused significant increases in IgM
      against ECA. Priming with ECA or SWAP caused significant elevation in IgG against
      ECA. In Western blotting, ECA-IMS recognized 16, 33, 38 and 94 kDa ECA peptides
      that cross-reacted with CAP-IMS. ECA peptides at 30 and 38 kDa cross-reacted
      among ECA, SWAP and SEA-IMS. CAP peptides at 40, 71, 85 and 97 kDa cross-reacted
      with ECA-IMS. A 59 kDa SWAP peptide cross-reacted with ECA. SEA peptides at
      approximately 55, 96 and 101 kDa cross-reacted with ECA-IMS. Immunization with
      ECA, CAP, SWAP or SEA caused significant increases in mesentric lymph nodes (MLN)
      CD4+, CD8+ -T cells and MLN-B cells. For thymocytes, CD4+ -T cells significantly
      increased upon immunization with ECA and SWAP while CD8+-T cells significantly
      increased upon immunization with SWAP. CONCLUSION: It is necessary to include E.
      coli antigens as controls while establishing schistosomal antigens-based
      diagnostic tests to ensure the specificity of the detected immune responses.
      Characterization of the cross-reactive ECA antigens with protective potential
      against S. mansoni infection remains a future research objective.

PMID- 19759477
TI  - Seroprevalence of parvovirus B19 among pregnant women in Tripoli, Libya.
AB  - BACKGROUND: Human parvovirus B19 has been implicated as a primary etiologic agent
      of erythema infectiosum (fifth disease) and aplastic crisis in patients with
      chronic haemolytic anemias. Human parvovirus B19 is known to be associated with
      adverse effects on fetuses such as hydrops fetalis, intrauterine fetal death, and
      chronic anaemia in immunocompromized individuals. The objective of this study was
      to assess the seroprevalence of human parvovirus B19 among the pregnant women in
      Tripoli, Libya. METHODOLOGY: A total number of 150 participants were included in
      the study, consisting of women of child-bearing age ranging from 18 to 41 years,
      and divided into age groups as follows: < or = 21 years, 22-27, 28-32, 33-37, and
      > or = 38 years. Specific IgM and IgG antibodies were measured using a commercial
      ELISA kit. RESULTS: IgG was observed to be prevalent (61%) among the women of
      child-bearing age. The sero-prevalence of IgM was found to be 5% overall and
      there was no detectable IgM in the age group between 33 and 37. CONCLUSION: The
      presence of IgG and absence of IgM indicate immunity to primary infection, but a
      significant percentage of child-bearing aged women are at risk of primary
      infection with parvovirus B19 which could adversely affect their pregnancy.

PMID- 19759478
TI  - Wound infections secondary to snakebite.
AB  - BACKGROUND: The study was performed to identify the important bacterial pathogens
      responsible for wound infections secondary to snakebite and to determine their
      antimicrobial susceptibility. METHODOLOGY: All cases of wound infection secondary
      to snakebite were included in this retrospective study. Infected tissues were
      surgically debrided and inoculated on blood agar and MacConkey agar for aerobic
      bacterial culture, followed by antimicrobial susceptibility testing of the
      isolates by Kirby-Bauer disk diffusion method. RESULTS: Staphylococcus aureus
      (32%) was the most common isolate followed by Escherichia coli (15%);
      monomicrobial infections were more frequent than polymicrobial infections. The
      majority of the isolates were antibiotic sensitive. Ciprofloxacin, an oral drug
      covering both Gram-positive and Gram-negative isolates, was the most frequently
      prescribed antibiotic. The patients responded well to the treatment. CONCLUSION:
      The results of this study will be helpful in deciding the empirical antibiotic
      therapy in cases of wound infection secondary to snakebite in regions of
      Southeast Asia.

PMID- 19759479
TI  - Staphylococcus aureus recovery from cotton towels.
AB  - BACKGROUND: Staphylococcus aureus is an emerging pathogen afflicting healthy
      individuals without known risk factors, and methicillin-resistant Staphylococcus
      aureus has been shown to colonize multiple family members sharing households.
      Because household items such as towels are often shared by family members, this
      study investigated whether cotton towel absorbency or washing conditions affect
      Staphylococcus aureus cell viability or cell retention, and whether the levels
      may be sufficient for person-to-person transmission. METHODOLOGY: Staphylococcus
      aureus ATCC 25923 was added to a 48 mm(2) template area on three cotton towel
      types (terry, pima, and Egyptian), and subjected to hand washing, without manual
      wringing, in three conditions (water only, bleach addition, or liquid detergent
      addition). Serial dilutions plated onto mannitol salt plates quantified bacteria
      for inoculations, pre- and post-wash water samples, towel surfaces, and hand
      transfer. Hand transfer of bacteria was determined on towels immediately, one,
      24, and 48 hours post inoculation. RESULTS: Bleach (p < or = .05) was the most
      effective at reducing bacterial viability on all towel types compared to
      detergent and water. Although not statistically significant, more Staphylococcus
      colonies were recovered from higher absorbency towels and from inside directly
      inoculated template areas. A paired t-test showed a difference between immediate
      and one-hour CFUs versus 24- and 48-hour recoveries (0.0002) for hand transfers.
      CONCLUSIONS: Cell viability decreased for over 48 hours on towels, but sufficient
      quantities may remain for colonization. More absorbent towels may harbor more
      Staphylococci than less absorbent ones, and may serve as a transmission mechanism
      for the bacterium.

PMID- 19759480
TI  - Prevalence of multi-gastrointestinal infections with helminth, protozoan and
      Campylobacter spp. in Guatemalan children.
AB  - BACKGROUND: The prevalence of multi-infections with helminthes, protozoans and
      Campylobacter spp. in Guatemalan children is a reflection of differences in the
      risk factors related to pathogen transmission. METHODOLOGY: Two hundred and
      eighty-nine fecal samples were collected from children of the Guatemalan
      highlands and patterns of pathogen occurrences were evaluated using an
      immunoassay for Campylobacter spp., a formalin-ether concentration followed by
      observation of unstained slides for helminthes and trichome stains of fecal
      smears for protozoans. Specimens were examined microscopically using 100, 400 and
      1000x magnification. RESULTS: Prevalence of Ascaris lumbricoides, Campylobacter
      spp., Giardia duodenalis, Entamoeba histolytica/E. dispar and Trichuris trichiura
      were 55.1%, 30.8%, 21.5%, 19.8% and 19.4%, respectively. Overall, the prevalence
      of at least one intestinal pathogen was 85.5%. Multi-infections were found in 43%
      of the children harboring pathogens. CONCLUSIONS: Infections with Campylobacter
      spp., E. histolytica/E. dispar, T. trichiura and G. duodenalis were closely
      associated with the presence of co-infection with A. lumbricoides. T. trichiura
      infection was related to co-infection with A. lumbricoides and Campylobacter spp.
      Infections with G. duodenalis and T. trichiura were related to co-infections with
      either Campylobacter spp. or E. histolytica/E. dispar. The prevalence of multi
      gastrointestinal infections with helminthes, protozoans and Campylobacter spp. in
      children was found to be related to age and gender.

PMID- 19759481
TI  - Detection of Hepatitis C virus and Human immunodeficiency virus in expatriates in
      Saudi Arabia by antigen-antibody combination assays.
AB  - BACKGROUND: The simultaneous detection of antigen and antibody was originally
      described for the early detection of the human immunodeficiency virus (HIV). The
      same approach was applied to detect the hepatitis C virus (HCV). The aim of this
      work was to use the antigen and antibody combination assay for the detection of
      HCV and HIV infections in expatriates in Eastern Saudi Arabia. METHODOLOGY: The
      study group (N = 875) included expatriate workers of both sexes who were
      undergoing mandatory pre-employment testing. Detection of anti-HCV antibodies,
      HCV core antigen, HCV viral RNA, HIV antigens and antibodies was conducted using
      commercially available kits. RESULTS: Of the 875 samples that were screened for
      HCV-specific antibodies, four (0.46%) tested positive (two from Pakistan, one
      from India, and one from the Philippines) and two (0.23%) were equivocal (one
      from Egypt and one from Nepal). All four samples that were positive for HCV
      specific antibodies also tested positive using HCV RNA assay and the HCV antigen
      antibody combination assay. The two samples that were equivocal tested positive
      using the HCV RNA assay and the HCV antigen-antibody combination assay. Of the
      875 samples that were tested for HIV antibodies, only one (0.11%) sample gave
      repeatedly positive results. The same sample also tested repeatedly positive
      using the HIV combination assay. These results were subsequently confirmed by HIV
      western blot assay. CONCLUSIONS: Our study indicates that the addition of antigen
      detection to the screening of HCV and HIV may lower the risk of transmission of
      these viruses in the host country and contribute to the overall control of HCV
      and HIV in Saudi Arabia.

PMID- 19759482
TI  - Brucellosis mimicking enteric fever.
AB  - Brucellosis is a systemic infection with multiple presentations. Despite its oral
      transmission and gastrointestinal pathogenesis, systemic symptoms are usually
      more prominent than gastrointestinal complaints. We report a patient with enteric
      fever caused by Brucella melitensis.

PMID- 19759483
TI  - A case of meningitis caused by Streptococcus pyogenes in a previously healthy
      woman.
AB  - BACKGROUND: Streptococcus pyogenes is a well-known cause of a variety of clinical
      infections including local symptoms such as tonsillopharyngitis, cervical
      lymphadenitis, otitis media, cellulites, erysipelas, as well as more severe
      diseases such as scarlet fever, osteomyelitis, necrotizing fasciitis, sepsis, and
      toxic shock syndrome. However, acute bacterial meningitis caused by this pathogen
      is unusual. OBJECTIVE: We report a case of group A streptococcus (GAS) meningitis
      in a previously healthy woman with a dramatically rapid course and fatal outcome.
      CASE: A 41-year-old previously healthy woman presented a history of fever,
      headache, vomiting, and sore throat of three days' duration. Neurological
      examination revealed diminished consciousness and neck rigidity. The
      cerebrospinal fluid (CSF) was turbid with 10,000 leukocytes/mm(3). Direct
      examination of CSF showed Gram-positive cocci in chains, and cultures yielded S.
      pyogenes. Blood cultures yielded growth of S. pyogenes. The patient was treated
      initially with ceftriaxone (4 g/day) and the control CSF examination was not
      changed on the third day, so vancomycin (2 g/day) was added to the treatment;
      however, she died on the fourth day of the treatment. CONCLUSION: S. pyogenes
      meningitis is uncommon and the incidence seems to be persistently low;
      nevertheless, clinicians should be aware that sporadic cases may occur and may
      have a fulminant course with a relevant neurological sequel.

PMID- 19759484
TI  - Prevalence of Trypanosomosis of small ruminants in Guangua district of Awi Zone,
      northwestern Ethiopia.

PMID- 19759485
TI  - Preliminary bibliometric evaluation of scientific publications produced in Latin
      America in the field of tropical and infectious diseases using SciELO.

PMID- 19759486
TI  - Food-borne botulism in Argentina.
AB  - Botulism is a severe neuroparalytic disease caused by Clostridium botulinum
      toxins. Although the disease is uncommon it is a cause of great concern due to
      its high rate of mortality. Food-borne outbreaks of botulism occur worldwide and
      require immediate public health attention and acute care resources. Analysis of
      outbreaks showed that the food products most often involved were fermented fish
      products in Alaska; home-canned food, oil preservation and restaurant sauce in
      the rest of the United States (US) and in London and; and home-canned vegetables,
      airtight packed food with inappropriate refrigeration, and aerosols in Argentina.
      The diagnosis is based only on clinical findings matching the disease and
      previous exposure to suspicious food. Botulism must be immediately identified as
      even one case suggests the start of an epidemic and should be treated as a public
      health emergency. Therefore, the purpose of the following review is to recognize
      the risks associated with the consumption of potentially dangerous foods, and to
      encourage prevention by seeking to make all public health professionals aware of
      the dangers of this potentially lethal disease.

PMID- 19759487
TI  - Breast brucellosis in Taif, Saudi Arabia: cluster of six cases with emphasis on
      FNA evaluation.
AB  - BACKGROUND: Brucellosis is an endemic zoonosis seen in a variety of geographical
      locations such as the Middle East and Latin American and Mediterranean countries.
      Brucellosis is hyper-endemic in Saudi Arabia with an incidence of 5.4 per 1000
      per year. Breast involvement very rarely occurs as a focal complication of
      brucellosis. METHODOLOGY: We report six cases of breast brucellosis retrieved
      from the files of the patients. Fine needle aspiration (FNA) was performed on all
      patients. In all cases direct smears were made at the patient's side for
      assessment of sample quality. Cytospin and cell block preparation was done and
      Gram, periodic acid-Schiff and Ziel-Nelson stains were done on all samples.
      Microbiological analysis included routine fungal and bacterial culture for
      tuberculosis. RESULTS: Age range was 20 to 48 years with a median of 22 years.
      Two patients gave history of raw milk ingestion, one was lactating, and one
      patient was pregnant. Cytomorphologic features of brucellosis in the breast
      include an abscess-like background with granulomatous inflammation. Cytology of
      the patients presented with breast abscess showed predominant neutrophilic
      infiltrate compatible with acute pyogenic inflammation. Culture was positive for
      B. melitensis in all cases. CONCLUSION: Brucellosis should be kept in mind in the
      differential diagnosis of breast abscess in endemic areas where ingestion of
      unpasteurized milk and milk products is common. Needle aspiration establishes a
      preliminary diagnosis and has the advantage of material submission for
      microbiologic cultures and provides focal treatment along with long-term combined
      antibacterial treatment for the control of systemic infection.

PMID- 19759488
TI  - The role of unpasteurized "hawked" milk in the transmission of brucellosis in
      Eldoret municipality, Kenya.
AB  - BACKGROUND: Brucellosis is a zoonotic disease that continues to infect many
      people worldwide. Though its mortality rate is low, long convalescent periods
      associated with brucellosis translate into reduced socio-economic capacity of the
      people affected. Human brucellosis is mostly transmitted from animals. In Kenya,
      the prevalence of the disease has increased recently, along with the increased
      hawking of unpasteurized milk. The extent of the risk such raw milk poses to
      human health with respect to brucellosis is unknown. This study investigates the
      possibility of brucellosis being transmitted through unprocessed milk sold by
      hawkers in Eldoret municipality. METHODOLOGY: In this cross-sectional study, 130
      samples of unpasteurized pooled milk from hawkers and 14 pasteurized milk samples
      were collected from shops in selected estates using cluster and simple random
      sampling techniques. All samples were subjected to the Brucella Milk Ring Test
      (MRT) for screening. A milk consumption questionnaire was administered to
      households in the selected estates to establish their milk sources and
      consumption patterns. Data analysis involved comparing computed percentages of
      different variables. RESULTS: A high proportion of households (77.5%) consume
      unpasteurized milk from hawkers. However, no antibody to Brucella was detected in
      any of the milk samples collected. CONCLUSION: We find no evidence that hawked
      milk in Eldoret is responsible for transmitting brucellosis to consumers. More
      research in the potential transmission of brucellosis through milk consumption is
      recommended.

PMID- 19759489
TI  - High mortality among patients with positive blood cultures at a children's
      hospital in Tbilisi, Georgia.
AB  - BACKGROUND: The etiology and outcomes of blood-stream infections (BSI) among
      paediatric patients is not well described in resource-limited countries including
      Georgia. METHODOLOGY: Patients with positive blood cultures at the largest
      paediatric hospital in the country of Georgia were identified by review of the
      medical and laboratory records of patients who had blood for cultures drawn
      between January 2004 and June 2006. RESULTS: Of 1,693 blood cultures obtained
      during the study period, 338 (20%) were positive; of these, 299 were included in
      our analysis. The median age was 14 days from a range of 2 days to 14 years of
      which 178 (60%) were male; 53% of the patients with a positive culture were
      admitted to the Neonatal Intensive Care Unit (NICU). Gram-negative bacilli (GNB)
      represented 165 (55%) of 299 cultures. Further speciation of 135 (82%) of 165
      Gram-negative rod (GNR) was not possible because of lack of laboratory capacity.
      Overall, mortality was 30% (90 of 299). Among the 90 children who died, 80 (89%)
      were neonates and 68 (76%) had BSI caused by Gram-negative organisms. In
      multivariate analysis, independent risk factors for in-hospital mortality
      included an age of less than 30 days (OR=4.00, 95% CI 1.89-8.46) and having a
      positive blood culture for a Gram-negative BSI (OR = 2.38, 95% CI 1.32-4.29).
      CONCLUSIONS: A high mortality rate was seen among children, particularly
      neonates, with positive blood cultures at the largest paediatric hospital in
      Georgia. Because of limited laboratory capacity, microbiological identification
      of common organisms known to cause BSI in children was not possible and
      susceptibility testing was not performed. Improving the infrastructure of
      diagnostic microbiology laboratories in countries with limited resources is
      critical in order to improve patient care and clinical outcomes, and from a
      public health standpoint, to improve surveillance activities.

PMID- 19759490
TI  - Nosocomial Burkholderia cepacia infections in a Turkish university hospital: a
      five-year surveillance.
AB  - BACKGROUND: Burkholderia cepacia has the potential to cause fatal infections in
      ICUs, and multidrug resistance makes them a serious threat in hospital settings.
      The aim of this study was to evaluate the epidemiology of B. cepacia infections
      in our hospital. METHODOLOGY: The incidence, clinical characteristics,
      antimicrobial susceptibility, and outcomes of nosocomial B. cepacia infections
      during a five-year period were retrospectively analysed according to the
      infection control committee records. RESULTS: A total of 39 cases with nosocomial
      B. cepacia infection were included in the study. B. cepacia was identified from
      0.7% of the nosocomial isolates. Its incidence was 0.26 per 1,000 admissions with
      53.8% crude mortality rate. The most frequent nosocomial B. cepacia infection was
      pneumonia (58.9%), followed by bloodstream infections (25.6%), surgical site
      infections (7.6%), urinary tract infections, (5.1%), and skin-soft tissue
      infections (2.5%). Nosocomial B. cepacia infections were most commonly observed
      in intensive care units (61.5%). The most active antimicrobial agents were
      piperacillin-tazobactam, cefoperazone-sulbactam, and carbapenems. CONCLUSIONS:
      The incidence of nosocomial B. cepacia infections was rare in our hospital, and
      no outbreak was detected during the study period. However, infections caused by
      B. cepacia should be taken into consideration because of their high mortality due
      to multidrug resistance in ICU settings.

PMID- 19759491
TI  - Analysis of isoniazid, streptomycin and ethambutol resistance in Mycobacterium
      tuberculosis isolates from Morocco.
AB  - BACKGROUND: Drug-resistant tuberculosis is a major problem worldwide. Based on
      the knowledge of specific mutations occurring in Mycobacterium tuberculosis
      genome, drug resistance can be detected earlier. The aim of this study was to
      determine the prevalence of the most common mutations associated with resistance
      to Isoniazid (INH), Streptomycin (SM) and Ethambutol (EMB) in Mycobacterium
      tuberculosis isolates from Morocco in order to select target mutations to develop
      tests for rapid detection of drug-resistant Mycobacterium tuberculosis Moroccan
      isolates. METHODOLOGY: A total of 199 M. tuberculosis isolates collected from the
      National Tuberculosis Reference Laboratory in Morocco were subject to katG, inhA,
      rrs, rpsL and emb mutation analysis by PCR probe-based assay. The genotypic
      results were then compared to drug susceptibility testing results for the
      corresponding drugs. RESULTS: Among 66 phenotypically INH resistant isolates,
      80.3% (53/66) were found to be genotypically INH resistant from which 77.3%
      (51/66) and 3% (2/66) had respective mutations in katG315 and inhp-15 codons. Of
      the 58 phenotypically SM resistant isolates, genotypic SM resistance was
      confirmed in 17.2% (10/58) cases. Nucleotide mutations at codons 43 and 88 of
      rpsL gene and at codon 512 of rrs gene were found respectively in 12.1% (7/58);
      1.7% (1/58) and 3.4% (2/58) of the phenotypically SM resistant Mycobacterium
      tuberculosis isolates. Finally, mutations at codon 306 of embB gene were
      identified in 42.3% (11/26) of Mycobacterium tuberculosis isolates phenotypically
      EMB resistant. CONCLUSION: This study showed that a large proportion of
      Mycobacterium tuberculosis resistant isolates from Morocco carry a large number
      of mutations in different codons (especially katG315, embB306 and rpsL43) of the
      corresponding genes associated with drug resistance. Thus, molecular analysis
      based on the identification of such mutations is useful but not fully sufficient
      to predict all drug resistance cases. Based on these results, rapid drug
      resistance genotyping can be used as an adjunct to the traditional culture based
      methods in reference laboratories.

PMID- 19759492
TI  - Extended spectrum AmpC and metallo-beta-lactamases in Serratia and Citrobacter
      spp. in a disc approximation assay.
AB  - OBJECTIVES: This study aimed to develop a novel model for detection of extended
      spectrum beta-lactamase (ESBL), AmpC and metallo-beta-lactamase (MBL) producing
      Serratia and Citrobacter species using cefoperazone sulbactam as well as other
      inducer-substrate combinations in a disc approximation assay. In the absence of
      molecular tools in developing countries, we attempted to standardize simple
      phenotypic techniques for detection of beta-lactamases to allow effective patient
      care in our countries. These techniques have been scarcely used in Serratia and
      Citrobacter spp., which are emerging as significant pathogens in our region.
      METHODOLOGY: Clinical isolates of Serratia and Citrobacter were tested for ESBL
      production. Cefoperazone (CP)/cefoperazone sulbactam (CPS), piperacillin
      (PIP)/piperacillin-tazobactam (TZP) and ceftazidime (CAZ)/ceftazidime-clavulanic
      acid (CAZ-CLAV) combinations were compared for their ability to detect ESBL
      producers phenotypically. Multi-drug resistant strains were further tested for
      detection of inducible/derepressed AmpC mutants by a disc approximation assay.
      Isolates were screened for MBL production by Imipenem (IMI). MBL production was
      confirmed using Ethylenediaminetetraacetic acid (EDTA) in a double disc synergy
      assay and Hodge test. Minimal inhibitory concentration (MIC) was performed for
      CP, CPS and IMI by agar dilution method for all isolates of Serratia and
      Citrobacter spp. RESULTS: Thirty-three percent of isolates of Serratia spp. and
      35.4% of Citrobacter spp. were ESBL producers. CPS was a more sensitive inducer
      of ESBL than TZP and CAZ/CAZ-CLAV. AmpC producers were detected in 25.6% of the
      isolates of Serratia spp. (40% inducible and 60% derepressed mutants) and in
      35.4% of the isolates of Citrobacter spp. (33% inducible and 66% derepressed
      mutants). Six isolates (four class B and two class A) of Serratia and eight
      isolates (seven class B and one class A) of Citrobacter spp. were MBL producers.
      Multiple mechanisms co-existed in eight isolates of Serratia and 15 isolates of
      Citrobacter spp. CPS was more effective in identifying ESBLs and inducible AmpC
      producers as well as type 1 carbapenemases than TZP and CAZ-CLAV were able to
      identify inducible AmpC producers. CONCLUSIONS: The high prevalence of ESBL,
      AmpC, and MBL in Serratia and Citrobacter species in this study suggests that
      detection of these by phenotypic methods in the absence of more specific
      molecular tests should be actively considered in not only developing countries
      but also in the developed world as this approach can lead to timely and
      appropriate antibiotic treatment. CPS may be advised due to the triple advantage
      of detection of all three types of beta-lactamases.

PMID- 19759493
TI  - Extended spectrum beta-lactamases (ESBL) in Escherichia coli and Klebsiella
      pneumoniae: trends in the hospital and community settings.
AB  - BACKGROUND: To assess the prevalence of extended spectrum beta-lactamase (ESBL)
      producing Escherichia coli and Klebsiella strains in nosocomial and community
      acquired infections. METHODOLOGY: The study was conducted at a centralized
      microbiology laboratory in the Eastern Province of Saudi Arabia. Laboratory
      records (January 2004 - December 2005) were assessed. Associated resistance to a
      panel of antibiotics was determined. RESULTS: A total of 6,750 Gram-negative
      organisms were assessed for ESBL-phenotype. ESBL was detected in 6% (409/6,750)
      of isolates, the majority of which were E. coli (83%). ESBL producers were
      significantly higher among isolates from in-patients 15.4% (143/927) versus out
      patients (4.5%; 266/5,823); p < 0.05. Old age (older than 60 years) represented a
      significant risk for having an ESBL-producing pathogen. Urine was the major
      source of ESBL isolates in in-patients (46.1%) and out-patients (74.4%). The
      proportion of urinary E. coli isolates which were ESBL producers was
      significantly higher among in-patients (53/506; 10.4%) compared to out-patients
      (182/4,074; 4.4%); p<0.05. Old age (older than 60 years) represented a
      significant risk for having an ESBL-producing pathogen. Urine was the major
      source of ESBL isolates in in-patients (46.1%) and out-patients (74.4%). The
      proportion of urinary E. coli isolates which were ESBL producers was
      significantly higher among in-patients (53/506; 10.4%) compared to out-patients
      (182/4,074; 4.4%); p<0.05. Among in-patients, 60% of the ESBL associated
      infections were nosocomial. All were sensitive to imipenem but high levels of
      resistance to gentamicin, amikacin, amoxicillin-clavulanic acid and ciprofloxacin
      was shown. CONCLUSION: The findings document evidence of the spread of
      multiresistant ESBL-producers into the community. This has significant
      implications for patient management, and indicates the need for increased
      surveillance and molecular characterization of these isolates.

PMID- 19759494
TI  - Molecular characterization of ESBL-producing Shigella sonnei isolates from
      patients with bacilliary dysentery in Lebanon.
AB  - BACKGROUND: Emergence of extended-spectrum beta-lactamases (ESBLs) in Shigella
      species imparting resistance to third-generation cephalosporins is a growing
      concern worldwide. The aim of this study is to molecularly characterize the newly
      emerging beta-lactam resistant Shigella sonnei, specifically ESBLs in Lebanon,
      and compare them to beta-lactam sensitive isolates. METHODOLOGY: We compared five
      beta-lactam-resistant S. sonnei isolates to six isolates susceptible to beta
      lactams. Presence of ESBLs was established by the combination disk method. PCR
      amplification and sequence analysis of the beta-lactamase-encoding genes, along
      with other antimicrobial resistance genes, were performed. The localization of
      beta-lactamase genes was established by conjugation experiments. Beta-lactamase
      gene transcription levels were determined by real-time RT-PCR. Molecular typing
      was performed by pulsed-field gel electrophoresis (PFGE). RESULTS: Four of five
      beta-lactam resistant isolates were extended spectrum beta-lactamase producers.
      These harbored the bla-CTX-M-15 gene borne on a 70 Kb plasmid and class 2
      integron genes on their chromosomes. The bla-CTX-M-15 gene was flanked by an
      insertion element ISEcp1. A chromosomal bla-TEM-1 gene was detected in one beta
      lactam resistant Shigella isolate and two of the ESBL producing isolates. The bla
      CTX-M-15 gene transcription levels were increased in EBSL isolates exposed to
      subinhibitory concentrations of ceftazidime. PFGE analysis revealed that the four
      bla-CTX-M-15 positive isolates were nonclonal but two of them shared genotypes
      with -lactam susceptible isolates. CONCLUSION: Dissemination of broad-spectrum
      beta-lactam resistance in Shigella sonnei is mediated by bla-CTX-M-15 through
      horizontal plasmid transfer rather than by clonal spread of the resistant
      isolates. Expression of this gene is further induced in the presence of
      ceftazidime.

PMID- 19759495
TI  - Endemic dengue fever: a seldom recognized hazard for Pakistani children.
AB  - BACKGROUND: Dengue fever (DF) has gained prominence as an epidemic disease in
      Pakistan in the recent years. However, little data exists to show its likely
      endemic nature. METHODOLOGY: We retrospectively analyzed blood for dengue IgM on
      samples obtained during a community-based surveillance for febrile illnesses in
      two slum areas of Karachi, Pakistan, between June 1999 and December 2001. In this
      period, no epidemic of DF occurred in the city. Participants were children older
      than 16 years who had fever >or=38 degrees C for more than 72 hours and in whom
      other common infections were excluded, based on clinical examination and
      laboratory tests (blood culture, urinalysis, complete blood count, Typhidot test
      and peripheral blood film for malaria). RESULTS: One hundred and fourteen blood
      samples were analyzed for dengue IgM ELISA, out of which 54 (47.4%) tested
      positive. The incidence of DF in this community was possibly as high as 185 (95%
      CI: 145 - 242) per hundred thousand population/year. Older children (10 - 15
      years) appeared 5.5 times more likely to be affected than their younger (0 - 5
      years) counterparts. CONCLUSIONS: DF is probably endemic in children in slums of
      Karachi, and likely to have high incidence rate. Older children are more
      susceptible to the disease. Further prospectively designed research is needed to
      confirm these findings. Until that time, DF may be included in the differential
      diagnosis of fever without focus in children in Karachi slums even in non
      epidemic periods.

PMID- 19759496
TI  - Superficial fungal infections: clinical and epidemiological study in adolescents
      from marginal districts of Lima and Callao, Peru.
AB  - BACKGROUND: Since limited data on superficial fungal infections in teenagers
      exist in our setting, this study provides the first description of the clinical
      and epidemiological characteristics of these infections among teenagers in Lima
      and Callao, Peru. METHODOLOGY: The study involved 1,387 adolescents in five
      public schools from June to November 2006. Participants were examined for
      superficial fungal lesions. Samples of skin scrapings for microbiological
      investigations were obtained from suspicious lesions. RESULTS: A total of 257
      subjects were identified with suspected superficial fungal infections.
      Microbiological assessment was positive for 166 of 257 (64.59%). The average
      prevalence was 12.61% with variation between different districts. Males were more
      affected (64%) than females (36%) (p = 0.001). Pet ownership, use of public
      baths, and wearing sneakers were identified as important risk factors. The
      majority (61.5%) of the subjects presented with itching although 38.5% were
      asymptomatic. Tinea pedis was observed in 62.6%, onychomycosis in 24% and
      pityriasis versicolor in 10.8%. Dermatophytes were isolated in 105 cases with T.
      rubrum being identified in 86 cases (59.7%), T. mentagrophytes in 14 (9.7%) and
      yeast in 39 (23.4%). Malassezia spp. was found by direct examination in 18 cases
      (12.5%), C. kruseii in 8 cases (5.6%), and C. albicans in 2 cases (1.4%). Mixed
      infections were found in 22 cases. CONCLUSIONS: Superficial fungal infection
      manifesting as tinea pedis, onychomycosysis and tinea versicolor is prevalent in
      our setting. As many infections remain asymptomatic, regular examination of this
      population is advocated. The associated risk factors for these infections also
      need to be addressed.

PMID- 19759497
TI  - Dual infection with dengue virus 3 and human immunodeficiency virus 1 in Havana,
      Cuba.
AB  - Although dengue virus (DEN) endemic regions overlap with human immunodeficiency
      virus 1 (HIV) high incidence areas, little has been documented on HIV and DEN
      mixed infection. Here we report DEN/HIV concurrent infections recorded during the
      DEN-3 epidemic in 2001-2002 in Havana. Serologic-confirmed DEN is described in
      two HIV-infected subjects with dengue fever symptoms. Although patients had
      dengue disease, the CD4+ cells remained within normal levels and no accelerated
      progression of HIV disease was observed. To our knowledge, DEN cases caused by
      DEN-3 in HIV-infected individuals have not been reported previously. Further
      research is needed to diagnose this likely underreported mixed viral infection in
      DEN endemic areas.

PMID- 19759498
TI  - First case of extensive spinal cord infection with Aspergillus nidulans in a
      child with chronic granulomatous disease.
AB  - Chronic granulomatous disease (CGD) is characterized by a defect in phagocytic
      cells that lead to recurrent bacterial and fungal infections. The etiology of
      most common fungal infections in CGD are Aspergillus species. Aspergillus
      nidulans is one of several species of Aspergillus with low pathogenicity.
      However, it was reported to cause fatal invasive Aspergillosis in patients with
      CGD. Here we report the first cured invasive Aspergillus nidulans infection with
      extensive involvement of the spinal cord in a five-year-old child with CGD.

PMID- 19759499
TI  - Controversial role of smallpox on historical positive selection at the CCR5
      chemokine gene (CCR5-Delta 32).

PMID- 19759500
TI  - On the spread of the novel influenza A (H1N1) virus in Mexico.
AB  - A novel influenza A H1N1 virus of swine origin is responsible for the influenza
      epidemic affecting Mexico, the United States of America (USA), and 39 other
      countries. While the origin of this emerging pathogen remains uncertain, an
      increase in the reported incidence of respiratory diseases was noted during March
      2009 at the town of La Gloria, in the southeastern state of Veracruz, Mexico. So
      far, this is the first community in which a case of novel influenza A H1N1 virus
      has been identified. Further cases were rapidly detected in other areas of Mexico
      and elsewhere. Initially, the atypical respiratory disease outbreak caused great
      uncertainty posing a challenge to the Mexican health system. Control measures
      such as social distancing, timely medical care, and personal hygiene have so far
      proven effective in containing the outbreak, resulting in a decline of the number
      of new cases. To the best of our knowledge, it appears that the virus might not
      be as virulent or contagious as previously thought. Here we provide a description
      of the influenza epidemic spread in Mexico. As the virus disseminates worldwide,
      there is concern about the possibility of a new reassortment resulting in a more
      pathogenic strain that will pose a threat for every country. The influenza
      epidemic provided lessons that underscore the importance of epidemiologic
      surveillance and preparedness. Further investigation to address questions about
      this new virus and conditions for its spread is warranted.

PMID- 19759501
TI  - Influenza pandemics: a historical retrospect.

PMID- 19759502
TI  - Carbapenem resistance in Acinetobacter baumannii: the molecular epidemic features
      of an emerging problem in health care facilities.
AB  - Acinetobacter baumannii is an opportunistic gram-negative pathogen with
      increasing relevance in a variety of nosocomial infections especially among
      intensive-care-unit (ICU) patients. Carbapenems have been widely used to treat
      serious multidrug-resistant A. baumannii infections; however, incidences of
      carbapenem-resistant A. baumannii are rising in several parts of the world and
      large and sustained outbreaks caused by such bacteria have been described.
      Carbapenem-resistant A. baumannii epidemics are sustained by clusters of highly
      similar strains that successfully spread among different cities and countries;
      their resistance phenotype is mainly due to the acquisition of carbapenem
      hydrolyzing class D beta-lactamase (CHDL) genes flanked by insertion sequence
      (IS) elements. Multi-facility outbreaks can be also sustained by inter-hospital
      transfer of colonized patients. Here, we review the global epidemiology of
      carbapenem-resistant A. baumannii, with the emphasis on the molecular
      epidemiology and genetic characterization of carbapenem resistance in epidemic
      strains.

PMID- 19759503
TI  - Detection of icaA, icaD genes and biofilm production by Staphylococcus aureus and
      Staphylococcus epidermidis isolated from urinary tract catheterized patients.
AB  - BACKGROUND: Staphylococci are a common cause of catheter-associated urinary tract
      infections. The present study evaluated biofilm forming capacity and the presence
      of both icaA and icaD genes among staphylococci strains isolated from patients
      undergoing ureteral catheterization. METHODOLOGY: Different bacterial strains
      were isolated from urine and stents segments collected from 100 patients. Strains
      were identified by traditional microbiological methods. Stents were examined for
      biofilm using a scanning electron microscope (SEM). Staphylococcal isolates were
      tested for their ability to produce biofilm using the tissue culture plate assay
      method (TCP). The presence of icaA and icaD genes was determined by PCR
      technique. RESULTS: Fifty-three staphylococcal strains were isolated and
      identified from 284 samples (18.7%). Forty-six staphylococcal strains were
      isolated from stent segment cultures while only seven strains were isolated from
      urine samples at the day of stent removal. S. aureus represented 6.3%, and S.
      epidermidis represented 12.3%. Out of the 18 S. aureus strains, 15 (83.3%) were
      biofilm producers and out of 35 S. epidermidis strains, 31 (88.6%) were biofilm
      producers. Staphylococcal strains were further classified as high (56.6%),
      moderate (30.2%) and non biofilm producers (13.2%). All biofilm producing strains
      were positive for icaA and icaD genes, and all biofilm negative strains were
      negative for both genes. CONCLUSION: Staphylococci isolated from catheter
      segments showed a higher extent of biofilm production than that isolated from
      urine samples. All biofilm producing staphylococci were positive for icaA and
      icaD genes, which indicates the important role of ica genes as virulence markers
      in staphylococcal infections associated with urinary catheterization.

PMID- 19759504
TI  - Hand hygiene practices in a neonatal intensive care unit in Ghana.
AB  - BACKGROUND: Compliance with hand hygiene recommendations is the most important
      measure in preventing health care-associated infections. The objective of this
      study was to assess the nature of patient contact and the hand hygiene practices
      of nurses and physicians in the neonatal intensive care unit in a tertiary
      hospital in Ghana. METHODOLOGY: Unobtrusive observation of patient contact, hand
      hygiene practices, and hand washing technique among nurses and physicians
      attending randomly selected newborns for five hours daily for two weeks. Patient
      contact categorized as low-risk or high-risk. Hand hygiene practice before and
      after patient contact categorized as clean uncontaminated, clean recontaminated,
      new gloves, unchanged gloves. Compliance to alcohol rub use assessed. RESULTS:
      The patient to nurse/physician ratio varied from 9:1 to 12:1. There were 97
      patient contacts of which 49 were high-risk and 48 low-risk. Most (73%) patient
      contacts were from nurses. Compliance to hand hygiene recommendations before
      versus after patient contact was 15.4% versus 38.5% for physicians and 14.1%
      versus 9.9% for nurses. Gloves were used for 60.8% patient contacts (85.7% high
      risk, 35.4% low-risk); however, compliance to recommended procedure occurred in
      only 12.2% of high-risk contacts and none of the low-risk contacts. Gloves were
      not changed between patients in 43.7% of high-risk contacts and 88.2% of low-risk
      contacts. Hand washing protocol was generally followed. Alcohol hand rub was
      always available but was not used for hand hygiene. CONCLUSIONS: Hand hygiene
      compliance of physicians and nurses was low. Gloves and alcohol rub were not used
      according to recommended guidelines. Incorporating effective education programs
      that improve adherence to hand hygiene guidelines into the continuing education
      curriculum of health professionals is recommended.

PMID- 19759505
TI  - A multicentre study of doctors' approaches to the diagnosis and treatment of
      tuberculosis in Turkey.
AB  - BACKGROUND: Inappropriate anti-tuberculosis (TB) treatment, particularly at the
      beginning of the disease, is a major cause of drug resistance. This survey was
      performed to evaluate doctors' approaches to the diagnosis and treatment of TB.
      METHOD: The study was conducted in 12 cities, each from a different geographical
      region of Turkey. A prepared questionnaire about their academic careers and
      experience in TB and its treatment was distributed to the doctors. RESULTS: The
      research group consisted of 1,112 doctors. The mean age was 32.7 +/- 6.6 years.
      The results showed that 75.9% of the doctors had insufficient knowledge about TB.
      The results of the study further showed that chest specialists, female doctors,
      physicians who work in a first stage hospital, doctors who had previously
      diagnosed TB and those who had access to a microbiology laboratory had a better
      level of knowledge about tuberculosis and its treatment than other doctors.
      CONCLUSION: A great diversity was seen between daily practice of doctors and
      national guidelines about TB. Educational programmes conducted by specialists in
      TB control may help to standardize and increase the knowledge of TB.

PMID- 19759506
TI  - Status of zinc in pulmonary tuberculosis.
AB  - BACKGROUND: To study the status of zinc as a micronutrient in pulmonary
      tuberculosis, in our population, with the aim to see the effectiveness of
      therapy. METHODOLOGY: This prospective study includes 50 patients with pulmonary
      tuberculosis and 30 subjects as the control group. The patients were placed into
      three stages (1 to 3) on the basis of chest radiographic findings. Serum zinc
      levels were estimated before, during, and after completion of antituberculosis
      therapy. RESULTS: Statistically significant fall in serum zinc levels was seen
      with advanced age and disease, and the levels improved after initiation of
      antituberculosis therapy. CONCLUSION: Estimation of serum zinc levels is an
      important tool in diagnosis and monitoring of response to treatment in pulmonary
      tuberculosis, and even a booster of the immunological mechanisms if instituted
      during the course of treatment.

PMID- 19759507
TI  - Hepatitis B and C virus co-infection in Nigerian patients with HIV infection.
AB  - INTRODUCTION: We set out to determine the seroprevalence of hepatitis B and
      hepatitis C viruses among human immunodeficiency virus infected individuals and
      its impact on pattern of presentation. METHODOLOGY: A serological study for
      hepatitis B and hepatitis C viruses was performed on 260 HIV-positive
      individuals. These patients were tested for the presence of hepatitis B surface
      antigen and anti-hepatitis C virus (HCV) antibody. RESULTS: Thirty (11.5%)
      patients tested positive for hepatitis B surface antigen, six (2.3%) tested
      positive for anti-hepatitis C virus antibody, four (1.5%) were positive for both
      hepatitis B surface antigen and anti-hepatitis C virus and the overall prevalence
      was 15.4% . Individuals younger than 40 years of age were more affected, and the
      odds ratio of a female being co-infected was 1.2, 25% versus 75% p value = 0.03.
      The prevalence of HIV and hepatitis co-infection rises with age except for
      hepatitis C. There was no significant difference in the mean levels of liver
      enzymes (AST, ALT) among the various groups. The groups differ significantly in
      their mean CD4 count: it was lowest for those co-infected with hepatitis B and
      hepatitis C; 106 cells/mm(3), 171 cells/mm(3) for those with HIV alone; and the
      highest value of 260 cells/mm(3) was obtained in those who tested positive for
      anti-HCV. Scarification marks and multiple blood transfusions were more common
      among those infected. There was no case of intravenous drug abuse identified.
      CONCLUSION: This low frequency of HIV/HCV co-infection is probably due to the
      uncommon intravenous drug abuse in this population. Co-infection with hepatitis B
      virus is common among our HIV-infected patients and should be a major
      consideration in the initiation and choice of therapy.

PMID- 19759508
TI  - Trend in seroprevalence of Hepatitis B virus infection among blood donors of
      coastal Karnataka, India.
AB  - BACKGROUND: Hepatitis B is one of the transfusion transmissible infections. The
      prevalence of this infection varies across the different geographies. Noting the
      trend in seroprevalence is useful to assist the preventive strategies. The aim of
      this study was to determine the trend of seroprevalence of hepatitis B in costal
      Karnataka over a three-year period. METHODOLOGY: The study was conducted at the
      blood bank of a tertiary care hospital serving predominantly the people of
      coastal Karnataka. A retrospective analysis of blood donors over a period of
      three years was done to assess the seroprevalence and the trend of hepatitis B
      infection. ELISA was used to detect the hepatitis B surface antigen in the donors
      as a marker of infection. RESULTS: A total of 30,428 blood donors were studied.
      189 (0.62%) were positive, which comes under the "low prevalence ( < 2%) zone"
      per World Health Organization (WHO) guidelines. A decreasing trend over three
      years was seen. Replacement donors and male blood donors showed higher
      seropositivity compared to voluntary donors and female donors. Chi-square test
      was used to calculate the significance of difference between the groups.
      CONCLUSION: Coastal Karnataka has a low prevalence of hepatitis B in blood donors
      with a decreasing trend over the last three-year period.

PMID- 19759509
TI  - The prevalence of resistance-associated mutations to protease and reverse
      transcriptase inhibitors in treatment-naive (HIV1)-infected individuals in
      Casablanca, Morocco.
AB  - BACKGROUND: The widespread use of antiretroviral agents and the growing
      occurrence of HIV-1 strains resistant to these drugs have given rise to serious
      concerns regarding the transmission of resistant viruses to newly infected
      persons, which may reduce the efficacy of a first-line antiretroviral therapy.
      METHODOLOGY: RNA was extracted from plasma samples of 98 treatment-naive
      individuals with a plasma HIV RNA viral load of at least 1,000 copies/ml. Both
      protease (pr) and reverse transcriptase (rt) were amplified and sequenced using
      an automated sequencer. National Agency for AIDS Research (ANRS) and Stanford HIV
      database algorithms were used for interpretation of resistance data. RESULTS: In
      the protease segment, various minor mutations were present in the majority of the
      sequenced samples with high frequencies. Only two major mutations, M46L and V82L,
      were separately found in three individuals of 71 (4.2%) with one carrying both
      mutations. In the reverse transcriptase gene, no NNRTIs-associated resistance
      mutations were detected. Only one patient of 70 (1.4%) carried the F77L mutation
      that is associated with NRTIs resistance. Genetic subtyping revealed that 74.6%
      of samples were infected with subtype B, 15.5% with CRF02_AG, 4.2% with CRF01_AE,
      1.4% with C, 2.8% with G and 1.4% with subtype F2. CONCLUSIONS: The low
      prevalence of major mutations associated with resistance to antiretroviral drugs
      (ARVs) among drug-naive individuals studied suggests that the routine of drug
      resistance testing may be unnecessary for all Moroccan individuals newly
      diagnosed or all patients beginning antiretroviral therapy. Nevertheless,
      continuous surveillance is required since greater access to antiretroviral drugs
      is expected in Morocco.

PMID- 19759510
TI  - Characteristics of the immune response during acute brucellosis in Sprague-Dawley
      rats.
AB  - BACKGROUND: Brucella is a facultative, intracellular pathogen that causes severe
      disease in animals and humans. Immunity against Brucella involves both humoral
      and cellular responses. To investigate the characteristics of immune response in
      acute brucellosis in Sprague-Dawley (SD) rats, IgG and its subclass specific
      immunoglobulins' (IgG1 and IgG2a) response in sera against B. abortus biotype 1
      infection were studied. METHODOLOGY: Thirty-six rats were inoculated
      intraperitoneally with 0.1 ml apyrogenic saline containing 1x10(10) colony
      forming unit (CFU) of B. abortus biotype 1 Korean bovine isolate. Four rats were
      used as uninfected controls. The sera were collected from infected rats at 3, 7,
      14, 21, 28, 35, 42, 49, and 56 days post infection (DPI) and screened for
      Brucella specific antibody response by the rose bengal plate test (RBPT). IgG and
      its subclass specific immunoglobulins' (IgG1 and IgG2a) response in the sera were
      measured by a lipopolysaccharide (LPS) based indirect enzyme-linked immunosorbent
      assay (IELISA). RESULTS: Brucella specific IgG, IgG1 and IgG2a responses in the
      sera of infected rats were detected from 3 DPI by IELISA. IgG and IgG1
      concentrations in sera reached the peak level at 35 DPI, and then the
      concentrations gradually declined to the end of the experiment. IgG2a
      concentrations in the sera remained almost constant from 7 DPI until the end of
      this study. CONCLUSION: In acute brucellosis, IgG2a response (indicative of a Th1
      response) was found to be significantly dominant over IgG1 response (indicative
      of Th2 response) (P < 0.001).

PMID- 19759511
TI  - Susceptibility of Mexican isolates of yeasts and moulds to amphotericin B and
      triazole antifungals.
AB  - BACKGROUND: Resistance to antifungal drugs, especially towards triazoles, is
      commonly referred to by clinicians, but data on its prevalence in developing
      countries is limited. METHODOLOGY: To determine the prevalence of triazole
      resistance amongst pathogenic yeasts and moulds, we assessed the in vitro
      susceptibility of 250 isolates from hospitalized patients at five Mexican cities
      towards amphotericin B, fluconazole and voriconazole, by E-test. RESULTS: All
      yeasts were susceptible to voriconazole, according to E-test interpretive
      criteria (MIC < or = 1 microg/mL), and all filamentous or dimorphic fungi also
      had voriconazole MIC < or = 1 microg/mL, except for one isolate each of Mucor sp.
      and Acremonium sp. Candida krusei and one isolate of C. glabrata were resistant
      to fluconazole, a drug that had MIC > or = 192 microg/mL for filamentous fungi.
      Although no breakpoints for amphotericin B are available, all three C. krusei,
      2/25 C. glabrata, 3/22 C. parapsilosis and 1/108 C. albicans had MIC > or = 2
      microg/mL. CONCLUSION: In vitro, voriconazole is active against yeasts and moulds
      commonly causing severe mycoses in Mexico.

PMID- 19759512
TI  - Miliary tuberculosis accompanying paravertebral tuberculosis abscess in an
      adolescent.
AB  - Although miliary tuberculosis (TB) is well known, the incidence of miliary TB
      accompanying paravertebral abscess is extremely rare in adolescent children. We
      report a case of paravertebral TB abscess and miliary TB in a 17-year-old male
      initially presenting with fever, general weakness, back pain, sweating, cough,
      dyspnea and weight loss. The patient was diagnosed as paravertebral TB abscess
      and miliary TB. The anti-tuberculous drugs were started and the follow-up imaging
      showed that the lesions had disappeared without surgery. Although seldom
      observed, TB should be kept in mind in the differential diagnosis of
      paravertebral abscess.

PMID- 19759513
TI  - Bilateral pedal edema in an HIV patient: Lopinavir/Ritonavir-containing treatment
      regimen as a potential cause?
AB  - A large number of patients are switched to second-line antiretroviral therapy,
      especially in resource limited settings. Lopinavir/Ritonavir is the main drug
      used in second-line treatment regimens. We describe a patient attending an HIV
      treatment centre in Kampala, Uganda, who presented with bilateral non-tender
      pitting inflammatory edema two weeks after switching to a Lopinavir/Ritonavir
      containing second-line treatment regimen. The lack of an alternate explanation
      led us to suspect that Lopinavir/Ritonavir was potentially responsible for the
      edema.

PMID- 19759514
TI  - TNF-alpha drives remodeling of blood vessels and lymphatics in sustained airway
      inflammation in mice.
AB  - Inflammation is associated with blood vessel and lymphatic vessel proliferation
      and remodeling. The microvasculature of the mouse trachea provides an ideal
      opportunity to study this process, as Mycoplasma pulmonis infection of mouse
      airways induces widespread and sustained vessel remodeling, including enlargement
      of capillaries into venules and lymphangiogenesis. Although the mediators
      responsible for these vascular changes in mice have not been identified, VEGF-A
      is known not to be involved. Here, we sought to determine whether TNF-alpha
      drives the changes in blood vessels and lymphatics in M. pulmonis-infected mice.
      The endothelial cells, but not pericytes, of blood vessels, but not lymphatics,
      were immunoreactive for TNF receptor 1 (TNF-R1) and lymphotoxin B receptors. Most
      TNF-R2 immunoreactivity was on leukocytes. Infection resulted in a large and
      sustained increase in TNF-alpha expression, as measured by real-time quantitative
      RT-PCR, and smaller increases in lymphotoxins and TNF receptors that preceded
      vessel remodeling. Substantially less vessel remodeling and lymphangiogenesis
      occurred when TNF-alpha signaling was inhibited by a blocking antibody or was
      silenced in Tnfr1-/- mice. When administered after infection was established, the
      TNF-alpha-specific antibody slowed but did not reverse blood vessel remodeling
      and lymphangiogenesis. The action of TNF-alpha on blood vessels is probably
      mediated through direct effects on endothelial cells, but its effects on
      lymphangiogenesis may require inflammatory mediators from recruited leukocytes.
      We conclude that TNF-alpha is a strong candidate for a mediator that drives blood
      vessel remodeling and lymphangiogenesis in inflammation.

PMID- 19759515
TI  - Endogenous glucocorticoids and impaired insulin signaling are both required to
      stimulate muscle wasting under pathophysiological conditions in mice.
AB  - Muscle wasting is associated with a number of pathophysiologic conditions,
      including metabolic acidosis, diabetes, sepsis, and high angiotensin II levels.
      Under these conditions, activation of muscle protein degradation requires
      endogenous glucocorticoids. As the mechanism(s) underlying this dependence on
      glucocorticoids have not been identified, we analyzed the effects of
      glucocorticoids on muscle wasting in a mouse model of acute diabetes.
      Adrenalectomized, acutely diabetic mice given a physiologic dose of
      glucocorticoids exhibited decreased IRS-1-associated PI3K activity in muscle and
      progressive muscle atrophy. These responses were related to increased association
      of PI3K with the glucocorticoid receptor (GR). In mice with muscle-specific GR
      deletion (referred to as MGRKO mice), acute diabetes minimally suppressed IRS-1
      associated PI3K activity in muscle and did not cause muscle atrophy. However,
      when a physiologic dose of glucocorticoids was given to mice with muscle-specific
      IR deletion, muscle protein degradation was accelerated. Fluorescence resonance
      energy transfer and an in vitro competition assay revealed that activated GRs
      competed for PI3K, reducing its association with IRS-1. Reexpression of WT GRs or
      those with a mutation in the nuclear localization signal in the muscle of MGRKO
      mice indicated that competition for PI3K was a prominent mechanism underlying
      reduced IRS-1-associated PI3K activity. This nongenomic influence of the GR
      contributes to activation of muscle protein degradation. We therefore conclude
      that stimulation of muscle proteolysis requires 2 events, increased
      glucocorticoid levels and impaired insulin signaling.

PMID- 19759516
TI  - SPDEF is required for mouse pulmonary goblet cell differentiation and regulates a
      network of genes associated with mucus production.
AB  - Various acute and chronic inflammatory stimuli increase the number and activity
      of pulmonary mucus-producing goblet cells, and goblet cell hyperplasia and excess
      mucus production are central to the pathogenesis of chronic pulmonary diseases.
      However, little is known about the transcriptional programs that regulate goblet
      cell differentiation. Here, we show that SAM-pointed domain-containing Ets-like
      factor (SPDEF) controls a transcriptional program critical for pulmonary goblet
      cell differentiation in mice. Initial cell-lineage-tracing analysis identified
      nonciliated secretory epithelial cells, known as Clara cells, as the progenitors
      of goblet cells induced by pulmonary allergen exposure in vivo. Furthermore, in
      vivo expression of SPDEF in Clara cells caused rapid and reversible goblet cell
      differentiation in the absence of cell proliferation. This was associated with
      enhanced expression of genes regulating goblet cell differentiation and protein
      glycosylation, including forkhead box A3 (Foxa3), anterior gradient 2 (Agr2), and
      glucosaminyl (N-acetyl) transferase 3, mucin type (Gcnt3). Consistent with these
      findings, levels of SPDEF and FOXA3 were increased in mouse goblet cells after
      sensitization with pulmonary allergen, and the proteins were colocalized in
      goblet cells lining the airways of patients with chronic lung diseases. Deletion
      of the mouse Spdef gene resulted in the absence of goblet cells in
      tracheal/laryngeal submucosal glands and in the conducting airway epithelium
      after pulmonary allergen exposure in vivo. These data show that SPDEF plays a
      critical role in regulating a transcriptional network mediating the goblet cell
      differentiation and mucus hyperproduction associated with chronic pulmonary
      disorders.

PMID- 19759517
TI  - Restimulation-induced apoptosis of T cells is impaired in patients with X-linked
      lymphoproliferative disease caused by SAP deficiency.
AB  - X-linked lymphoproliferative disease (XLP) is a rare congenital immunodeficiency
      that leads to an extreme, usually fatal increase in the number of lymphocytes
      upon infection with EBV. It is most commonly defined molecularly by loss of
      expression of SLAM-associated protein (SAP). Despite this, there is little
      understanding of how SAP deficiency causes lymphocytosis following EBV infection.
      Here we show that T cells from individuals with XLP are specifically resistant to
      apoptosis mediated by TCR restimulation, a process that normally constrains T
      cell expansion during immune responses. Expression of SAP and the SLAM family
      receptor NK, T, and B cell antigen (NTB-A) were required for TCR-induced
      upregulation of key pro-apoptotic molecules and subsequent apoptosis. Further,
      SAP/NTB-A signaling augmented the strength of the proximal TCR signal to achieve
      the threshold required for restimulation-induced cell death (RICD). Strikingly,
      TCR ligation in activated T cells triggered increased recruitment of SAP to NTB
      A, dissociation of the phosphatase SHP-1, and colocalization of NTB-A with CD3
      aggregates. In contrast, NTB-A and SHP-1 contributed to RICD resistance in XLP T
      cells. Our results reveal what we believe to be novel roles for NTB-A and SAP in
      regulating T cell homeostasis through apoptosis and provide mechanistic insight
      into the pathogenesis of lymphoproliferative disease in XLP.

PMID- 19759518
TI  - The inability to disrupt the immunological synapse between infected human T cells
      and APCs distinguishes HIV-1 from most other primate lentiviruses.
AB  - Viruses that infect T cells, including those of the lentivirus genus, such as HIV
      1, modulate the responsiveness of infected T cells to stimulation by interacting
      APCs in a manner that renders the T cells more permissive for viral replication.
      HIV-1 and other primate lentiviruses use their Nef proteins to manipulate the T
      cell/APC contact zone, the immunological synapse (IS). It is known that primate
      lentiviral Nef proteins differ substantially in their ability to modulate cell
      surface expression of the TCR-CD3 and CD28 receptors critical for the formation
      and function of the IS. However, the impact of these differences in Nef function
      on the interaction and communication between virally infected T cells and primary
      APCs has not been investigated. Here we have used primary human cells to show
      that Nef proteins encoded by HIV-2 and most SIVs, which downmodulate cell surface
      expression of TCR-CD3, disrupt formation of the IS between infected T cells and
      Ag-presenting macrophages or DCs. In contrast, nef alleles from HIV-1 and its
      simian precursor SIVcpz failed to suppress synapse formation and events
      downstream of TCR signaling. Our data suggest that most primate lentiviruses
      disrupt communication between virally infected CD4+ Th cells and APCs, whereas
      HIV-1 and its SIV precursor have largely lost this capability. The resulting
      differences in the levels of T cell activation and apoptosis may play a role in
      the pathogenesis of AIDS.

PMID- 19759519
TI  - The antiapoptotic protein Bcl-xL negatively regulates the bone-resorbing activity
      of osteoclasts in mice.
AB  - The B cell lymphoma 2 (Bcl-2) family member Bcl-xL has a well-characterized
      antiapoptotic function in lymphoid cells. However, its functions in other cells-
      including osteoclasts, which are of hematopoietic origin--and other cellular
      processes remain unknown. Here we report an unexpected function of Bcl-xL in
      attenuating the bone-resorbing activity of osteoclasts in mice. To investigate
      the role of Bcl-xL in osteoclasts, we generated mice with osteoclast-specific
      conditional deletion of Bcl-x (referred to herein as Bcl-x cKO mice) by mating
      Bcl-xfl/fl mice with mice in which the gene encoding the Cre recombinase has been
      knocked into the cathepsin K locus and specifically expressed in mature
      osteoclasts. Although the Bcl-x cKO mice grew normally with no apparent
      morphological abnormalities, they developed substantial osteopenia at 1 year of
      age, which was caused by increased bone resorption. Bcl-x deficiency increased
      the bone-resorbing activity of osteoclasts despite their high susceptibility to
      apoptosis, whereas Bcl-xL overexpression produced the opposite effect. In
      addition, Bcl-x cKO osteoclasts displayed increased c-Src activity, which was
      linked to increased levels of vitronectin and fibronectin expression. These
      results suggest that Bcl-xL attenuates osteoclastic bone-resorbing activity
      through the decreased production of ECM proteins, such as vitronectin and
      fibronectin, and thus provide evidence for what we believe to be a novel cellular
      function of Bcl-xL.

PMID- 19759520
TI  - Dual targeting of EGFR can overcome a major drug resistance mutation in mouse
      models of EGFR mutant lung cancer.
AB  - EGFR is a major anticancer drug target in human epithelial tumors. One effective
      class of agents is the tyrosine kinase inhibitors (TKIs), such as gefitinib and
      erlotinib. These drugs induce dramatic responses in individuals with lung
      adenocarcinomas characterized by mutations in exons encoding the EGFR tyrosine
      kinase domain, but disease progression invariably occurs. A major reason for such
      acquired resistance is the outgrowth of tumor cells with additional TKI-resistant
      EGFR mutations. Here we used relevant transgenic mouse lung tumor models to
      evaluate strategies to overcome the most common EGFR TKI resistance mutation,
      T790M. We treated mice bearing tumors harboring EGFR mutations with a variety of
      anticancer agents, including a new irreversible EGFR TKI that is under
      development (BIBW-2992) and the EGFR-specific antibody cetuximab. Surprisingly,
      we found that only the combination of both agents together induced dramatic
      shrinkage of erlotinib-resistant tumors harboring the T790M mutation, because
      together they efficiently depleted both phosphorylated and total EGFR. We suggest
      that these studies have immediate therapeutic implications for lung cancer
      patients, as dual targeting with cetuximab and a second-generation EGFR TKI may
      be an effective strategy to overcome T790M-mediated drug resistance. Moreover,
      this approach could serve as an important model for targeting other receptor
      tyrosine kinases activated in human cancers.

PMID- 19759521
TI  - Semi-automated Optical Heartbeat Analysis of small hearts.
AB  - We have developed a method for analyzing high speed optical recordings from
      Drosophila, zebrafish and embryonic mouse hearts (Fink, et. al., 2009). Our Semi
      automatic Optical Heartbeat Analysis (SOHA) uses a novel movement detection
      algorithm that is able to detect cardiac movements associated with individual
      contractile and relaxation events. The program provides a host of physiologically
      relevant readouts including systolic and diastolic intervals, heart rate, as well
      as qualitative and quantitative measures of heartbeat arrhythmicity. The program
      also calculates heart diameter measurements during both diastole and systole from
      which fractional shortening and fractional area changes are calculated. Output is
      provided as a digital file compatible with most spreadsheet programs.
      Measurements are made for every heartbeat in a record increasing the statistical
      power of the output. We demonstrate each of the steps where user input is
      required and show the application of our methodology to the analysis of heart
      function in all three genetically tractable heart models.

PMID- 19759522
TI  - Insulin teaches a new lesson in tolerance.

PMID- 19759524
TI  - Combination therapy with paricalcitol and trandolapril reduces renal fibrosis in
      obstructive nephropathy.
AB  - Growing evidence suggests that active vitamin D slows the progression of chronic
      kidney diseases. Here we compared the individual renal protective efficacy of
      paricalcitol and trandolapril (an angiotensin-converting enzyme inhibitor) in
      obstructive nephropathy, and examined any potential additive effects of their
      combination on attenuating renal fibrosis and inflammation. Mice underwent
      unilateral ureteral obstruction and were treated individually with paricalcitol
      or trandolapril or their combination. Compared to vehicle-treated controls,
      monotherapy with paricalcitol or trandolapril inhibited the expression and
      accumulation of fibronectin and type I and type III collagen, suppressed alpha
      smooth muscle actin, vimentin, and Snail1 expression, and reduced total collagen
      content in the obstructed kidney. Combination therapy led to a more profound
      inhibition of all parameters. Monotherapy also suppressed renal RANTES (regulated
      on activation, normal T cell expressed and secreted) and tumor necrosis factor
      (TNF)-alpha expression and inhibited renal infiltration of T cells and
      macrophages, whereas the combination had additive effects. Renin expression was
      induced in the fibrotic kidney and was augmented by trandolapril. Paricalcitol
      blocked renin induction in the absence or presence of trandolapril. Our study
      indicates that paricalcitol has renal protective effects, comparable to that of
      trandolapril, in reducing interstitial fibrosis and inflammation. Combination
      therapy had additive efficacy in retarding renal scar formation during
      obstructive nephropathy.

PMID- 19759525
TI  - Occurrence of adverse, often preventable, events in community hospitals involving
      nephrotoxic drugs or those excreted by the kidney.
AB  - Medication errors in patients with reduced creatinine clearance are harmful and
      costly; however, most studies have been conducted in large academic hospitals. As
      there are few studies regarding this issue in smaller community hospitals, we
      conducted a multicenter, retrospective cohort study in six community hospitals
      (100 to 300 beds) to assess the incidence and severity of adverse drug events
      (ADEs) in patients with reduced creatinine clearance. A chart review was
      performed on adult patients hospitalized during a 20-month study period with
      serum creatinine over 1.5 mg/dl who were exposed to drugs that are nephrotoxic or
      cleared by the kidney. Among 109,641 patients, 17,614 had reduced creatinine
      clearance, and in a random sample of 900 of these patients, there were 498
      potential ADEs and 90 ADEs. Among these ADEs, 91% were preventable, 51% were
      serious, 44% were significant, and 4.5% were life threatening. Of the potential
      ADEs, 54% were serious, 44% were significant, 1.6% were life threatening, and
      96.6% were not intercepted. All 82 preventable events could have been intercepted
      by renal dose checking. Our study shows that ADEs were common in patients with
      impaired kidney function in community hospitals, and many appear potentially
      preventable with renal dose checking.

PMID- 19759526
TI  - A prospective study of protein excretion using short-interval timed urine
      collections in patients with lupus nephritis.
AB  - The 24-h urine protein-to-creatinine ratio is the gold standard in evaluating
      proteinuria in lupus nephritis; however, the urine collection is inconvenient to
      the patient. Random spot urine protein-to-creatinine ratios, although convenient,
      have poor agreement with the 24-h ratios in these patients. Here, we sought to
      define a timed collection interval providing accurate and precise data and
      patient convenience. Urine from 41 patients, in 2 medical centers, with biopsy
      proven lupus nephritis was collected at 6-h intervals for 24 h. The protein-to
      creatinine ratio of each short collection was then compared with that of a 24-h
      collection made by combining the 6-h samples. A first morning void and spot urine
      samples were collected before and after the 24-h collection, respectively. There
      was significant diurnal variation with peak proteinuria at 6-12 h and nadir at 18
      24 h. Each 6-h collection showed excellent correlation and concordance with the
      24-h protein-to-creatinine ratio, but the 12-24-h interval had the best
      agreement. In contrast to the random spot urines, the first morning void also had
      excellent correlation and concordance, but underestimated the 24-h protein-to
      creatinine ratio. Our study shows that a 12-h overnight urine collection is the
      best surrogate, with excellent agreement with the 24-h protein-to-creatinine
      ratio, and it is convenient for patients. There was little variability between
      centers, an important feature for clinical trials.

PMID- 19759527
TI  - Experimental ischemia-reperfusion: biases and myths-the proximal vs. distal
      hypoxic tubular injury debate revisited.
AB  - Although the understanding of processes associated with hypoxic tubular cell
      injury has remarkably improved, controversies remain regarding the
      appropriateness of various animal models to the human syndrome of acute kidney
      injury (AKI). We herein compare available experimental models of hypoxic acute
      kidney damage, which differ both conceptually and morphologically in the
      distribution of tubular cell injury. Tubular segment types differ in their
      capacity to mount hypoxia-adaptive responses, mediated by hypoxia-inducible
      factors (HIFs), and in cell type-specific molecules shed into the urine, which
      may serve as early biomarkers for renal damage. These differences may be of value
      in the perception of the human AKI, its detection, and prevention.

PMID- 19759529
TI  - The glycine transporter-1 inhibitor SSR103800 displays a selective and specific
      antipsychotic-like profile in normal and transgenic mice.
AB  - Schizophrenia has been initially associated with dysfunction in dopamine
      neurotransmission. However, the observation that antagonists of the glutamate N
      methyl-D-aspartate (NMDA) receptor produce schizophrenic-like symptoms in humans
      has led to the idea of a dysfunctioning of the glutamatergic system via its NMDA
      receptor. As a result, there is a growing interest in the development of
      pharmacological agents with potential antipsychotic properties that enhance the
      activity of the glutamatergic system via a modulation of the NMDA receptor. Among
      them are glycine transporter-1 (GlyT1) inhibitors such as SSR103800, which
      indirectly enhance NMDA receptor function by increasing the glycine (a co-agonist
      for the NMDA receptor) levels in the synapse. This study aimed at investigating
      the potential antipsychotic-like properties of SSR103800, with a particular focus
      on models of hyperactivity, involving either drug challenge (ie, amphetamine and
      MK-801) or transgenic mice (ie, NMDA Nr1(neo-/-) and DAT(-/-)). Results showed
      that SSR103800 (10-30 mg/kg p.o.) blocked hyperactivity induced by the non
      competitive NMDA receptor antagonist, MK-801 and partially reversed spontaneous
      hyperactivity of NMDA Nr1(neo-/-) mice. In contrast, SSR103800 failed to affect
      hyperactivity induced by amphetamine or naturally observed in dopamine
      transporter (DAT(-/-)) knockout mice (10-30 mg/kg p.o.). Importantly, both
      classical (haloperidol) and atypical (olanzapine, clozapine and aripiprazole)
      antipsychotics were effective in all these models of hyperactivity. However,
      unlike these latter, SSR103800 did not produce catalepsy (retention on the bar
      test) up to 30 mg/kg p.o. Together these findings show that the GlyT1 inhibitor,
      SSR103800, produces antipsychotic-like effects, which differ from those observed
      with compounds primarily targeting the dopaminergic system, and has a reduced
      side-effect potential as compared with these latter drugs.

PMID- 19759528
TI  - Attention-deficit/hyperactivity disorder and attention networks.
AB  - Research attempting to elucidate the neuropathophysiology of attention
      deficit/hyperactivity disorder (ADHD) has not only shed light on the disorder
      itself, it has simultaneously provided new insights into the mechanisms of normal
      cognition and attention. This review will highlight and integrate this
      bidirectional flow of information. Following a brief overview of ADHD clinical
      phenomenology, ADHD studies will be placed into a wider historical perspective by
      providing illustrative examples of how major models of attention have influenced
      the development of neurocircuitry models of ADHD. The review will then identify
      major components of neural systems potentially relevant to ADHD, including
      attention networks, reward/feedback-based processing systems, as well as a
      'default mode' resting state network. Further, it will suggest ways in which
      these systems may interact and be influenced by neuromodulatory factors. Recent
      ADHD imaging data will be selectively provided to both illustrate the field's
      current level of knowledge and to show how such data can inform our understanding
      of normal brain functions. The review will conclude by suggesting possible
      avenues for future research.

PMID- 19759530
TI  - Invasive circuitry-based neurotherapeutics: stereotactic ablation and deep brain
      stimulation for OCD.
AB  - Psychiatric neurosurgery, specifically stereotactic ablation, has continued since
      the 1940s, mainly at a few centers in Europe and the US. Since the late 1990s,
      the resurgence of interest in this field has been remarkable; reports of both
      lesion procedures and the newer technique of deep brain stimulation (DBS) have
      increased rapidly. In early 2009, the US FDA granted limited humanitarian
      approval for DBS for otherwise intractable obsessive-compulsive disorder (OCD),
      the first such approval for a psychiatric illness. Several factors explain the
      emergence of DBS and continued small-scale use of refined lesion procedures. DBS
      and stereotactic ablation have been successful and widely used for movement
      disorders. There remains an unmet clinical need: current drug and behavioral
      treatments offer limited benefit to some seriously ill people. Understandings of
      the neurocircuitry underlying psychopathology and the response to treatment,
      while still works in progress, are much enhanced. Here, we review modern lesion
      procedures and DBS for OCD in the context of neurocircuitry. A key issue is that
      clinical benefit can be obtained after surgeries targeting different brain
      structures. This fits well with anatomical models, in which circuits connecting
      orbitofrontal cortex (OFC), medial prefrontal cortex (mPFC), basal ganglia, and
      thalamus are central to OCD pathophysiology and treatment response. As in
      movement disorders, dedicated interdisciplinary teams, here led by psychiatrists,
      are required to implement these procedures and maintain care for patients so
      treated. Available data, although limited, support the promise of stereotactic
      ablation or DBS in carefully selected patients. Benefit in such cases appears not
      to be confined to obsessions and compulsions, but includes changes in affective
      state. Caution is imperative, and key issues in long-term management of
      psychiatric neurosurgery patients deserve focused attention. DBS and contemporary
      ablation also present different patterns of potential benefits and burdens.
      Translational research to elucidate how targeting specific nodes in putative OCD
      circuitry might lead to therapeutic gains is accelerating in tandem with clinical
      use.

PMID- 19759531
TI  - Mechanisms of locomotor sensitization to drugs of abuse in a two-injection
      protocol.
AB  - A single exposure to psychostimulants or morphine is sufficient to induce
      persistent locomotor sensitization, as well as neurochemical and
      electrophysiological changes in rodents. Although it provides a unique model to
      study the bases of long-term behavioral plasticity, sensitization mechanisms
      remain poorly understood. We investigated in the mouse, a species suited for
      transgenic studies, the mechanisms of locomotor sensitization showed by the
      increased response to a second injection of drug (two-injection protocol of
      sensitization, TIPS). The first cocaine injection induced a locomotor
      sensitization that was completely context-dependent, increased during the first
      week, and persisted 3 months later. The induction of sensitized responses to
      cocaine required dopamine D1 and glutamate NMDA receptors. A single injection of
      the selective dopamine transporter blocker GBR12783 was sufficient to activate
      extracellular signal-regulated kinase (ERK) in the striatum to the same level as
      cocaine and to induce sensitization to cocaine, but not to itself. The induction
      of sensitization was sensitive to protein synthesis inhibition by anisomycin
      after cocaine administration. Morphine induced a pronounced context-dependent
      sensitization that crossed with cocaine. Sensitization to morphine injection was
      prevented in knockin mutant mice bearing a Thr-34-Ala mutation of DARPP-32, which
      suppresses its ability to inhibit protein phosphatase-1 (PP1), but not mutation
      of Thr-75 or Ser-130. These results combined with previous ones show that TIPS in
      mouse is a context-dependent response, which involves an increase in
      extracellular dopamine, stimulation of D1 and NMDA receptors, regulation of the
      cAMP-dependent and ERK pathways, inhibition of PP1, and protein synthesis. It
      provides a simple and sensitive paradigm to study the mechanisms of long-term
      effects of drugs of abuse.

PMID- 19759532
TI  - Serial mitogen-stimulated cytokine production from continuously ill patients with
      schizophrenia.
AB  - Aberrant activation of the immune system has been implicated in an increasingly
      large number of disease states and can influence cognition, mood, and memory.
      There is a long and controversial history of reports of immune activation
      associated with schizophrenia. In this study, we measured mitogen-stimulated
      cytokine levels serially in 100 medication-stabilized continuously ill subjects
      with schizophrenia and compared and contrasted them with mitogen-stimulated
      cytokine levels from 51 normal volunteers. The subjects with schizophrenia had
      consistently higher mitogen-stimulated IL-2 levels and lower IL-6 levels than the
      normal volunteers. These effects could not be explained by medications, smoking,
      or other clinical variables. We conclude that continuously symptomatic medication
      stabilized subjects with schizophrenia have a mitogen-stimulated cytokine
      expression pattern that is suggestive of ongoing immune activation.

PMID- 19759533
TI  - Genetic variation in IL28B and spontaneous clearance of hepatitis C virus.
AB  - Hepatitis C virus (HCV) infection is the most common blood-borne infection in the
      United States, with estimates of 4 million HCV-infected individuals in the United
      States and 170 million worldwide. Most (70-80%) HCV infections persist and about
      30% of individuals with persistent infection develop chronic liver disease,
      including cirrhosis and hepatocellular carcinoma. Epidemiological, viral and host
      factors have been associated with the differences in HCV clearance or
      persistence, and studies have demonstrated that a strong host immune response
      against HCV favours viral clearance. Thus, variation in genes involved in the
      immune response may contribute to the ability to clear the virus. In a recent
      genome-wide association study, a single nucleotide polymorphism (rs12979860) 3
      kilobases upstream of the IL28B gene, which encodes the type III interferon IFN
      3, was shown to associate strongly with more than a twofold difference in
      response to HCV drug treatment. To determine the potential effect of rs12979860
      variation on outcome to HCV infection in a natural history setting, we genotyped
      this variant in HCV cohorts comprised of individuals who spontaneously cleared
      the virus (n = 388) or had persistent infection (n = 620). We show that the C/C
      genotype strongly enhances resolution of HCV infection among individuals of both
      European and African ancestry. To our knowledge, this is the strongest and most
      significant genetic effect associated with natural clearance of HCV, and these
      results implicate a primary role for IL28B in resolution of HCV infection.

PMID- 19759534
TI  - Gene therapy for red-green colour blindness in adult primates.
AB  - Red-green colour blindness, which results from the absence of either the long-
      (L) or the middle- (M) wavelength-sensitive visual photopigments, is the most
      common single locus genetic disorder. Here we explore the possibility of curing
      colour blindness using gene therapy in experiments on adult monkeys that had been
      colour blind since birth. A third type of cone pigment was added to dichromatic
      retinas, providing the receptoral basis for trichromatic colour vision. This
      opened a new avenue to explore the requirements for establishing the neural
      circuits for a new dimension of colour sensation. Classic visual deprivation
      experiments have led to the expectation that neural connections established
      during development would not appropriately process an input that was not present
      from birth. Therefore, it was believed that the treatment of congenital vision
      disorders would be ineffective unless administered to the very young. However,
      here we show that the addition of a third opsin in adult red-green colour
      deficient primates was sufficient to produce trichromatic colour vision
      behaviour. Thus, trichromacy can arise from a single addition of a third cone
      class and it does not require an early developmental process. This provides a
      positive outlook for the potential of gene therapy to cure adult vision
      disorders.

PMID- 19759535
TI  - Integration of neuronal clones in the radial cortical columns by EphA and ephrin
      A signalling.
AB  - The cerebral cortex is a laminated sheet of neurons composed of the arrays of
      intersecting radial columns. During development, excitatory projection neurons
      originating from the proliferative units at the ventricular surface of the
      embryonic cerebral vesicles migrate along elongated radial glial fibres to form a
      cellular infrastructure of radial (vertical) ontogenetic columns in the
      overlaying cortical plate. However, a subpopulation of these clonally related
      neurons also undergoes a short lateral shift and transfers from their parental to
      the neighbouring radial glial fibres, and intermixes with neurons originating
      from neighbouring proliferative units. This columnar organization acts as the
      primary information processing unit in the cortex. The molecular mechanisms, role
      and significance of this lateral dispersion for cortical development are not
      understood. Here we show that an Eph receptor A (EphA) and ephrin A (Efna)
      signalling-dependent shift in the allocation of clonally related neurons is
      essential for the proper assembly of cortical columns. In contrast to the
      relatively uniform labelling of the developing cortical plate by various
      molecular markers and retrograde tracers in wild-type mice, we found alternating
      labelling of columnar compartments in Efna knockout mice that are caused by
      impaired lateral dispersion of migrating neurons rather than by altered cell
      production or death. Furthermore, in utero electroporation showed that lateral
      dispersion depends on the expression levels of EphAs and ephrin-As during
      neuronal migration. This so far unrecognized mechanism for lateral neuronal
      dispersion seems to be essential for the proper intermixing of neuronal types in
      the cortical columns, which, when disrupted, might contribute to neuropsychiatric
      disorders associated with abnormal columnar organization.

PMID- 19759536
TI  - Inhibitors selective for mycobacterial versus human proteasomes.
AB  - Many anti-infectives inhibit the synthesis of bacterial proteins, but none
      selectively inhibits their degradation. Most anti-infectives kill replicating
      pathogens, but few preferentially kill pathogens that have been forced into a non
      replicating state by conditions in the host. To explore these alternative
      approaches we sought selective inhibitors of the proteasome of Mycobacterium
      tuberculosis. Given that the proteasome structure is extensively conserved, it is
      not surprising that inhibitors of all chemical classes tested have blocked both
      eukaryotic and prokaryotic proteasomes, and no inhibitor has proved substantially
      more potent on proteasomes of pathogens than of their hosts. Here we show that
      certain oxathiazol-2-one compounds kill non-replicating M. tuberculosis and act
      as selective suicide-substrate inhibitors of the M. tuberculosis proteasome by
      cyclocarbonylating its active site threonine. Major conformational changes
      protect the inhibitor-enzyme intermediate from hydrolysis, allowing formation of
      an oxazolidin-2-one and preventing regeneration of active protease. Residues
      outside the active site whose hydrogen bonds stabilize the critical loop before
      and after it moves are extensively non-conserved. This may account for the
      ability of oxathiazol-2-one compounds to inhibit the mycobacterial proteasome
      potently and irreversibly while largely sparing the human homologue.

PMID- 19759537
TI  - Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling.
AB  - The stability of the Wnt pathway transcription factor beta-catenin is tightly
      regulated by the multi-subunit destruction complex. Deregulated Wnt pathway
      activity has been implicated in many cancers, making this pathway an attractive
      target for anticancer therapies. However, the development of targeted Wnt pathway
      inhibitors has been hampered by the limited number of pathway components that are
      amenable to small molecule inhibition. Here, we used a chemical genetic screen to
      identify a small molecule, XAV939, which selectively inhibits beta-catenin
      mediated transcription. XAV939 stimulates beta-catenin degradation by stabilizing
      axin, the concentration-limiting component of the destruction complex. Using a
      quantitative chemical proteomic approach, we discovered that XAV939 stabilizes
      axin by inhibiting the poly-ADP-ribosylating enzymes tankyrase 1 and tankyrase 2.
      Both tankyrase isoforms interact with a highly conserved domain of axin and
      stimulate its degradation through the ubiquitin-proteasome pathway. Thus, our
      study provides new mechanistic insights into the regulation of axin protein
      homeostasis and presents new avenues for targeted Wnt pathway therapies.

PMID- 19759538
TI  - Neural activity predicts attitude change in cognitive dissonance.
AB  - When our actions conflict with our prior attitudes, we often change our attitudes
      to be more consistent with our actions. This phenomenon, known as cognitive
      dissonance, is considered to be one of the most influential theories in
      psychology. However, the neural basis of this phenomenon is unknown. Using a
      Solomon four-group design, we scanned participants with functional MRI while they
      argued that the uncomfortable scanner environment was nevertheless a pleasant
      experience. We found that cognitive dissonance engaged the dorsal anterior
      cingulate cortex and anterior insula; furthermore, we found that the activation
      of these regions tightly predicted participants' subsequent attitude change.
      These effects were not observed in a control group. Our findings elucidate the
      neural representation of cognitive dissonance, and support the role of the
      anterior cingulate cortex in detecting cognitive conflict and the neural
      prediction of attitude change.

PMID- 19759539
TI  - p53 and metabolism.
AB  - Although metabolic alterations have been observed in cancer for almost a century,
      only recently have the mechanisms underlying these changes been identified and
      the importance of metabolic transformation realized. p53 has been shown to
      respond to metabolic changes and to influence metabolic pathways through several
      mechanisms. The contributions of these activities to tumour suppression are
      complex and potentially rather surprising: some reflect the function of basal p53
      levels that do not require overt activation and others might even promote, rather
      than inhibit, tumour progression.

PMID- 19759541
TI  - Sexual activity and erectile dysfunction in elderly men with angiographically
      documented coronary artery disease.
AB  - We studied the prevalence of erectile dysfunction (ED) in elderly men, aged 65
      years or above, with coronary artery disease (CAD) documented by coronary
      angiography. A total of 123 men (112 men with CAD and 11 men without CAD), mean
      age 74.6+/-5.9 years, was included. To detect ED and assess its severity, all
      participants were asked to complete the Sexual Health Inventory for Males (SHIM)
      questionnaire. Lack of sexual activity was more prevalent among men with CAD
      relative to men without CAD (31.3 vs 0.0%). Among the sexually active men, ED was
      more prevalent among men with CAD relative to men without CAD (85.7 vs 72.7%). A
      general linear model showed that age was the only factor associated with SHIM
      scores among the sexually active men with CAD (P=0.001). Other factors, such as
      the number of occluded coronary arteries, diabetes mellitus, hypertension,
      smoking, various medications and marital status, were not associated with SHIM
      scores in elderly men with CAD. We conclude that lack of sexual activity and ED
      are very common in elderly men with CAD. Among the sexually active men with CAD,
      ED severity is associated only with age.

PMID- 19759542
TI  - The effect of anti-tumor necrosis factor agents on sexual dysfunction in male
      patients with ankylosing spondylitis: a pilot study.
AB  - Sexual dysfunction is a common problem among patients with ankylosing spondylitis
      (AS). This study was an open-label study without placebo to assess sexual
      dysfunction in male patients with AS, and to determine whether sexual function
      might improve with the use of tumor necrosis factor (TNF)-alpha blockers. Twenty
      two males with AS (age, 29-48 years) were treated for 3 months with TNF-alpha
      blockers. Before and after treatment, Bath Ankylosing Spondylitis Disease
      Activity Index (BASDAI) was measured, and all patients completed the
      International Index of Erectile Function (IIEF) questionnaire, a self
      administered measure of sexual dysfunction with five domains: erectile function
      (EF), intercourse satisfaction (IS), orgasmic function (OF), sexual desire (SD)
      and overall satisfaction (OS). There were significant improvements in BASDAI
      after treatment with TNF-alpha blockers (P<0.001). Anti-TNF-alpha treated
      patients showed significant improvements in four out of the five IIEF domains
      (EF, P<0.001; IS, P<0.001; SD, P=0.006; OS, P=0.033). Among patients with
      erectile dysfunction, there were significant improvements in three IIEF domains
      (EF, P=0.006; IS, P=0.007; SD, P=0.018). Only IS domain of IIEF showed a
      significant correlation with BASDAI (partial correlation coefficient = -0.484,
      P=0.026). This study showed that anti-TNF-alpha therapy may improve sexual
      dysfunction in male AS patients, in addition to reducing disease activity.

PMID- 19759543
TI  - Erectile function in men with diabetes type 2: correlation with glycemic control.
AB  - Men with diabetes have an increased risk for erectile dysfunction (ED) than those
      without diabetes. The diabetes control and complications trial clearly showed
      that better long-term control of blood glucose in diabetes type 1 is associated
      with decreased frequency and delayed the onset of microvascular complications.
      The aim of this study is to explore the role of glycemic control, and its
      correlation to sexual function in patients with diabetes type 2. One hundred
      patients were selected for the study according to the following criteria: all the
      cases were presenting with diabetes type 2 as a single risk factor for ED, age
      being between 35 and 50 years and free of liver and kidney failure, and blood
      dyscrasis. The selected patients were evaluated for sexual function by asking the
      patients to complete the abridged form of the International Index of Erectile
      Function (IIEF). The evaluation of glycemic control was based on the measurement
      of hemoglobin A(1c) (HbA(1c)) values. Our results showed that the level of
      HbA(1c) is significantly higher with declining degrees of potency (P
      value=0.003). Also, there is an association between potency degree and glycemic
      control (P=0.002). We conclude that glycemic control is independently and
      inversely associated with ED in men with diabetes type 2.

PMID- 19759544
TI  - Yohimbine relaxes the human corpus cavernosum through a non-adrenergic mechanism
      involving the activation of K+ATP-dependent channels.
AB  - The mechanism by which yohimbine relaxes the human corpus cavernosum remains
      unclear. Using the human corpus cavernosum strips immersed in isometric baths
      containing Krebs-Henseleit solution, this study investigates the effect of
      yohimbine on the relaxation of the human corpus cavernosum through nitrergic
      pathways involving the activation of ATP-dependent potassium channels (K(ATP)).
      The maximal relaxation induced by yohimbine in the human corpus cavernosum strips
      pre-contracted with phenylephrine was 100+/-0% and only 30.5+/-5.0% when they
      were pre-contracted with 60-mM potassium (K(+)) solution. The maximal relaxation
      induced by yohimbine in phenylephrine pre-contracted tissues was significantly
      inhibited by tetrodotoxin, 1H-[1,2,4] oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) or
      7-nitroindazole (43.6, 36.1 and 42.6%, respectively). Neither the combination
      charybdotoxin-apamin nor tetraethylammonium altered the response of the human
      corpora cavernosa strips to yohimbine. Nevertheless, glibenclamide decreased the
      maximum relaxant response to yohimbine by 29.8% (P<0.05; n=12). The results
      suggest that yohimbine relaxes the human corpus cavernosum by a non-adrenergic,
      non-cholinergic mechanism, probably activating the nitrergic-soluble guanylate
      cyclase (NO-sGc) pathway and K(ATP).

PMID- 19759545
TI  - Long-term morbidities associated with vocal cord paralysis after surgical closure
      of a patent ductus arteriosus in extremely low birth weight infants.
AB  - OBJECTIVE: Determine associations between left vocal cord paralysis (LVCP) and
      poor respiratory, feeding and/or developmental outcomes in extremely low birth
      weight (ELBW) infants following surgical closure of a patent ductus arteriosus
      (PDA). STUDY DESIGN: ELBW infants who underwent PDA ligation between January 2004
      and December 2006 were identified. We compared infants with and without LVCP
      following ligation to determine relationships between LVCP and respiratory
      morbidities, feeding and growth difficulties and neurodevelopmental impairment at
      18 to 22-month follow-up. Student's t-test, Fisher's exact test and multivariable
      regression analyses were used to determine associations. RESULT: In all, 60 ELBW
      infants with a mean gestational age of 25 weeks and mean birth weight of 725 g
      had a PDA surgically closed. Twenty-two of 55 survivors (40%) were diagnosed with
      LVCP post-operatively. Infants with LVCP were significantly more likely to
      develop bronchopulmonary dysplasia (82 vs 39%, P=0.002), reactive airway disease
      (86 vs 33%, P<0.0001), or need for gastrostomy tube (63 vs 6%, P<0.0001).
      CONCLUSION: LVCP as a complication of surgical ductal ligation in ELBW infants is
      associated with persistent respiratory and feeding problems. Direct laryngoscopy
      should be considered for all infants who experience persistent respiratory and/or
      feeding difficulties following PDA ligation.

PMID- 19759546
TI  - Persistent inflammation and angiogenesis during wound healing in K14-directed
      Hoxb13 transgenic mice.
AB  - Chronic, nonhealing wounds and inadequate tissue repair characterized by
      excessive fibrosis continue to have a considerable negative effect on health and
      quality of life. Understanding the molecular events required for adequate
      healing, including the transcriptional control of wound repair, will be important
      for the development of future therapies. We previously showed that loss of Hoxb13
      from murine skin results in enhanced cutaneous wound healing, suggesting that
      Hoxb13 has a negative effect on wound repair. To test this, we generated skin
      specific Hoxb13 transgenic (TG) mice that overexpress Hoxb13 in the basal layer
      of the epidermis by the human keratin 14 promoter. Using these mice, we evaluated
      the effects of Hoxb13 overexpression on cutaneous wound healing. Transgenic
      wounds were characterized by persistence of the fibrin clot and prolonged
      inflammation. Notably, neutrophils, which had cleared from wild-type wounds, were
      still pronounced in TG wounds. Marked epidermal hyperplasia was observed at TG
      wound edges, and dermal vessels were grossly abnormal compared with wild-type
      mice. Both vascular endothelial growth factor and tumor necrosis factor-alpha
      were upregulated in Hoxb13 TG skin. Together, our results identify Hoxb13 as a
      potential important clinical target in wound healing and other pathologies
      characterized by abnormal or excessive inflammation, angiogenesis, or epidermal
      proliferation.

PMID- 19759547
TI  - Impact of NAD(P)H:quinone oxidoreductase-1 on pigmentation.
AB  - We obtained metastasized melanoma tissue from a primary acral lentiginous
      melanoma (ALM) patient and established a melanoma cell line named primary culture
      of melanoma cell derived from lymph node (PML)-1. PML-1 cells had a light brown
      color and decreased the expression of melanogenesis markers, including tyrosinase
      (TYR), microphthalmia-associated transcription factor, and tyrosinase-related
      protein-1. To identify genes differentially regulated in PML-1 melanoma cells, we
      performed DNA microarray and two-dimensional matrix-assisted laser desorption
      ionization-time of flight mass spectrometry analyses. Among the candidate genes
      identified, we chose NAD(P)H:quinone oxidoreductase-1 (NQO1) for further study.
      Reverse transcription-PCR and western blot analyses showed that NQO1 was markedly
      decreased in PML-1 cells and in several amelanotic melanoma cell lines. To
      investigate whether NQO1 affects the melanogenesis, we treated the cultured
      normal human melanocytes (NHMC) and zebrafish with NQO1 inhibitors, ES936 and
      dicoumarol. Interestingly, melanogenesis was significantly decreased by the
      addition of NQO1 inhibitors in both NHMC and zebrafish models. In contrast,
      overexpression of NQO1 using a recombinant adenovirus clearly induced
      melanogenesis, concomitantly with an increase of TYR protein level. These results
      suggest that NQO1 is a positive regulator of the pigmentation process.

PMID- 19759548
TI  - Downregulation of Fas gene expression in Sezary syndrome is associated with
      promoter hypermethylation.
AB  - Sezary Syndrome (SS) is an aggressive leukemic variant of primary cutaneous T
      cell lymphoma characterized by the presence of tumor or Sezary cells that
      generally display a mature memory T-cell immunophenotype. Sezary cells
      proliferate poorly and therefore their accumulation may be due to defective T
      cell homeostasis involving resistance to apoptosis. In this study, we analyzed
      Fas expression in CD4+ lymphocytes at the mRNA and protein levels in a large
      cohort of SS patients as compared with healthy controls. Fas mRNA expression was
      dysregulated in 34/47 patients, with significant under- and overexpression of Fas
      mRNA detected in 21 and 13 patients respectively (P<0.01). Examination of cell
      surface Fas expression showed correlation with the observed downregulation of
      mRNA in CD4+ T cells. Mutational analysis demonstrated that functional FAS gene
      mutations are rare. Moreover, 16 SS patients who showed significant under
      expression of Fas mRNA also showed significant positional hypermethylation within
      the FAS CpG island, which was not present in healthy controls or SS patients
      determined to have normal or overexpression of Fas mRNA. These data demonstrate
      that dysregulation of Fas expression is a common feature of SS, and provide a
      rationale for targeted therapies to restore the extrinsic Fas-dependent apoptotic
      pathway in this malignancy.

PMID- 19759549
TI  - Loss of epidermal Langerhans cells occurs in human papillomavirus alpha, gamma,
      and mu but not beta genus infections.
AB  - Human papillomaviruses (HPVs), which are contained in the alpha, beta, gamma, mu,
      and nu genera, differ in their oncogenic potential and their tropism for
      cutaneous or mucosal epidermis. Langerhans cells (LC), the only epidermal
      professional antigen-presenting cells, are readily detected in normal mucosal and
      cutaneous epithelium. The aim of this study is to determine whether LC loss,
      which has been reported for HPV16, occurs in other HPV genera and establish its
      significance in viral pathology. We found that, as for HPV16, LCs were reduced in
      lesions infected with high-risk mucosal (alpha7 and alpha9 species) and low-risk
      cutaneous (gamma and mu) types. Lesions infected with alpha10 low-risk genital
      types had reduced LC but contained epidermal LC patches, coincident with dermis
      localized regulatory T cells (T-regs). In contrast to other genera, LCs were
      common in the epidermis, and T-regs occupied the dermis of the potentially high
      risk cutaneous beta-HPV type infected lesions. Therefore, LC loss in the infected
      lesions occurred irrespective of tropism or oncogenic potential of the HPV type.
      LC depletion in the HPV-infected epidermis may create an environment that is
      permissive for viral persistence and in HPV lesions in which LCs are found, the
      presence of typically immunosuppressive T-regs may compensate for their continued
      presence.

PMID- 19759550
TI  - Induction of terminal differentiation in melanoma cells on downregulation of beta
      amyloid precursor protein.
AB  - The incidence of melanoma, the most aggressive type of skin cancer, is increasing
      dramatically, and an effective treatment for patients with advanced disease is as
      yet unavailable. Greater insight into the molecular features of primary and
      metastatic melanoma is required, particularly the identification of key
      regulatory genes that shield the tumor cells from terminal differentiation and
      apoptosis. The beta-amyloid precursor protein (APP) is a cell surface receptor
      and the transmembrane precursor of the Abeta-peptide, which has an important role
      in Alzheimer's disease. The study presented here provides evidence that APP is
      expressed at high levels in advanced-stage melanomas, and that the cells cleave
      APP and secrete sAPP. We show that blocking the expression of APP by RNA
      interference impairs the proliferation of metastatic melanoma cells and leads to
      their terminal and irreversible differentiation. In addition, suppressing APP
      expression in a metastatic melanoma cell line renders the cells susceptible to
      several chemotherapeutic agents. Targeting APP may thus constitute a new approach
      to the treatment of this disease.

PMID- 19759551
TI  - Coexisting NRAS and BRAF mutations in primary familial melanomas with specific
      CDKN2A germline alterations.

PMID- 19759552
TI  - Protein kinase C-dependent upregulation of miR-203 induces the differentiation of
      human keratinocytes.
AB  - Terminal differentiation of keratinocytes is a multistep process that requires a
      coordinated program of gene expression. We aimed to explore the possible
      involvement of a previously unreported class of non-coding RNA genes, microRNAs
      (miRNAs) in keratinocyte differentiation by using miRNA expression profiling. Out
      of 365 miRNAs tested, 7 showed significant change between keratinocytes cultured
      in low or high calcium concentration. The highest-ranked upregulated gene was miR
      203, whose expression was significantly upregulated in response to calcium and
      other inducers of keratinocyte differentiation such as 12-O-tetradecanoylphorbol
      13-acetate (TPA) and vitamin D(3). Differentiation-induced upregulation of miR
      203 expression was blocked by treatment with specific inhibitors of protein
      kinase C (PKC), GF109203X, and Ro31-8220. Moreover, our results showed that the
      activator protein-1 (AP-1) proteins c-Jun and JunB regulate miR-203 expression in
      keratinocytes. In contrast to inducers of keratinocyte differentiation, epidermal
      growth factor and keratinocyte growth factor suppressed miR-203 expression in
      keratinocytes below the basal level. Overexpression of miR-203 in keratinocytes
      resulted in enhanced differentiation, whereas inhibition of miR-203 suppressed
      calcium-induced terminal differentiation as judged by involucrin expression.
      These results suggest that upregulation of miR-203 in human keratinocytes is
      required for their differentiation and is dependent on the activation of the
      PKC/AP-1 pathway.

PMID- 19759554
TI  - Oligonucleotide array-CGH identifies genomic subgroups and prognostic markers for
      tumor stage mycosis fungoides.
AB  - Mycosis fungoide (MF) patients who develop tumors or extracutaneous involvement
      usually have a poor prognosis with no curative therapy available so far. In the
      present European Organization for Research and Treatment of Cancer (EORTC)
      multicenter study, the genomic profile of 41 skin biopsies from tumor stage MF
      (MFt) was analyzed using a high-resolution oligo-array comparative genomic
      hybridization platform. Seventy-six percent of cases showed genomic aberrations.
      The most common imbalances were gains of 7q33.3q35 followed by 17q21.1, 8q24.21,
      9q34qter, and 10p14 and losses of 9p21.3 followed by 9q31.2, 17p13.1, 13q14.11,
      6q21.3, 10p11.22, 16q23.2, and 16q24.3. Three specific chromosomal regions,
      9p21.3, 8q24.21, and 10q26qter, were defined as prognostic markers showing a
      significant correlation with overall survival (OS) (P=0.042, 0.017, and 0.022,
      respectively). Moreover, we have established two MFt genomic subgroups
      distinguishing a stable group (0-5 DNA aberrations) and an unstable group (>5 DNA
      aberrations), showing that the genomic unstable group had a shorter OS (P=0.05).
      We therefore conclude that specific chromosomal abnormalities, such as gains of
      8q24.21 (MYC) and losses of 9p21.3 (CDKN2A, CDKN2B, and MTAP) and 10q26qter (MGMT
      and EBF3) may have an important role in prognosis. In addition, we describe the
      MFt genomic instability profile, which, to our knowledge, has not been reported
      earlier.

PMID- 19759553
TI  - Genetic and environmental risk factors for childhood eczema development and
      allergic sensitization in the CCAAPS cohort.
AB  - Eczema is very common and increasing in prevalence. Prospective studies
      investigating environmental and genetic risk factors for eczema in a birth cohort
      are lacking. We evaluated risk factors that may promote development of childhood
      eczema in the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) birth
      cohort (n=762) of infants with at least one atopic parent. Objective
      environmental exposure data were available for each participant. At annual
      physical examinations, children underwent skin prick tests (SPTs), eczema was
      diagnosed by a clinician, and DNA was collected. Among Caucasian children, 39%
      developed eczema by age 3. Children with a pet dog were significantly less likely
      to have eczema at age one (odds ratio (OR)=0.62, 95% confidence interval (CI):
      0.40-0.97) or at both ages 2 and 3 (OR=0.54, 95% CI: 0.30-0.97). This finding was
      most significant among children carrying the CD14-159C/T CC genotype. Carriers of
      the CD14-159C/T and IL4Ralpha I75V single-nucleotide polymorphisms (SNPs) had an
      increased risk of eczema at both ages 2 and 3 (OR=3.44, 95% CI: 1.56-7.57),
      especially among children who were SPT+. These results provide new insights into
      the pathogenesis of eczema in high-risk children and support a protective role
      for early exposure to dog, especially among those carrying the CD14-159C/T SNP.
      The results also demonstrate a susceptibility effect of the combination of CD14
      and IL4Ralpha SNPs with eczema.

PMID- 19759555
TI  - Association of insulin-like growth factor-1 receptor gene polymorphisms with left
      ventricular mass and geometry in essential hypertension.
AB  - Stimulation of insulin-like growth factor (IGF)-1 receptor by IGF-1 and insulin
      strongly induces cardiomyocyte hypertrophy. In this study, we assessed the
      hypothesis that genetic variations of the IGF-1 receptor may be linked to the
      diversity of left ventricular (LV) structure in hypertensive patients. Genotypes
      in 12 single nucleotide polymorphisms (SNPs) of the IGF-1 receptor gene
      identified by direct sequencing were determined in 795 Japanese patients with
      essential hypertension. In echocardiographic examinations, LV mass index (LVMI)
      and relative wall thickness (RWT) were measured. Among 12 SNPs, promoter -328C>T
      and intron-13 275124A>C polymorphisms were significantly associated with LV
      hypertrophy (LVMI> or =125 g m(-2)) and concentric change (RWT> or =0.44),
      respectively. In allele frequencies, the C allele of -328C>T was related to LV
      hypertrophy, and the A allele of 275124A>C was related to LV concentric change.
      In fact, LVMI and prevalence of LV hypertrophy increased in CC genotype of 
      328C>T. RWT and prevalence of LV concentric change increased in AA genotype of
      275124A>C. A multiple logistic regression analysis revealed that the presence of
      CC genotype of -328C>T or AA genotype of 275124A>C was an independent determinant
      for LV hypertrophy or concentric change, respectively. Furthermore, the
      combination of CC of -328C>T and AA of 275124A>C genotypes was significantly
      associated with abnormal LV geometry, especially concentric hypertrophy. Our
      findings show that two SNPs of the IGF-1 receptor gene are related to LV
      hypertrophy in patients with essential hypertension, suggesting that the genetic
      variation of the IGF-1 receptor may be involved in the diversity of LV structure
      in hypertensives.

PMID- 19759556
TI  - TP53 mutations in myeloid malignancies are either homozygous or hemizygous due to
      copy number-neutral loss of heterozygosity or deletion of 17p.

PMID- 19759557
TI  - A different ontogenesis for chronic lymphocytic leukemia cases carrying
      stereotyped antigen receptors: molecular and computational evidence.
AB  - Chronic lymphocytic leukemia (CLL) is uniquely characterized by the existence of
      subsets of cases with quasi-identical, 'stereotyped' B-cell receptors (BCRs).
      Herein we investigate this stereotypy in 2662 patients with CLL, the largest
      series yet, using purpose-built bioinformatics methods based on sequence pattern
      discovery. Besides improving the identification of 'stereotyped' cases, we
      demonstrate that CLL actually consists of two different categories, based on the
      BCR repertoire, with important biological and ontogenetic differences. The first
      ( approximately 30% of cases) shows a very restricted repertoire and is
      characterized by BCR stereotypy (clustered cases), whereas the second includes
      cases with heterogeneous BCRs (nonclustered cases). Eleven major CLL clusters
      were identified with antigen-binding sites defined by just a few critically
      positioned residues, regardless of the actual immunoglobulin (IG) variable gene
      used. This situation is closely reminiscent of the receptors expressed by cells
      participating in innate immune responses. On these grounds, we argue that whereas
      CLL cases with heterogeneous BCRs likely derive from the conventional B-cell
      pool, cases with stereotyped BCRs could derive from progenitor cells
      evolutionarily adapted to particular antigenic challenges, perhaps intermediate
      between a true innate immune system and the conventional adaptive B-cell immune
      system, functionally similar to what has been suggested previously for mouse B1
      cells.

PMID- 19759558
TI  - A phase I/II trial of TLR-7 agonist immunotherapy in chronic lymphocytic
      leukemia.

PMID- 19759559
TI  - Extensive mutational status of genes and clinical outcome in pediatric acute
      myeloid leukemia.

PMID- 19759560
TI  - Different isoforms of the B-cell mutator activation-induced cytidine deaminase
      are aberrantly expressed in BCR-ABL1-positive acute lymphoblastic leukemia
      patients.
AB  - The main reason for the unfavorable clinical outcome of BCR-ABL1-positive acute
      lymphoblastic leukemia (ALL) is genetic instability. However, how normal B-cell
      precursors acquire the genetic changes that lead to transformation has not yet
      been completely defined. We investigated the expression of the activation-induced
      cytidine deaminase (AID) and its role in clinical outcome in 61 adult BCR-ABL1
      positive ALL patients. AID expression was detected in 36 patients (59%); it
      correlated with the BCR-ABL1 transcript levels and disappeared after treatment
      with tyrosine kinase inhibitors. Different AID splice variants were identified:
      full-length isoform; AIDDeltaE4a, with a 30-bp deletion of exon 4; AIDDeltaE4,
      with the exon 4 deletion; AIDins3, with the retention of intron 3; AIDDeltaE3-E4
      isoform without deaminase activity. AID-FL predominantly showed cytoplasmic
      localization, as did the AID-DeltaE4a and AID-DeltaE3E4 variants, whereas the C
      terminal-truncated AID-DeltaE4 showed a slightly increased nuclear localization
      pattern. AID expression correlated with a higher number of copy number
      alterations identified in genome-wide analysis using a single-nucleotide
      polymorphism array. However, the expression of AID at diagnosis was not
      associated with a worse prognosis. In conclusion, BCR-ABL1-positive ALL cells
      aberrantly express different isoforms of AID that may act as mutators outside the
      immunoglobulin (Ig) gene loci in promoting genetic instability.

PMID- 19759561
TI  - The function of the pleckstrin homology domain in BCR-ABL-mediated
      leukemogenesis.

PMID- 19759562
TI  - Dose-dependent restoration of dystrophin expression in cardiac muscle of
      dystrophic mice by systemically delivered morpholino.
AB  - We have earlier shown that antisense morpholino oligomers are able to restore
      dystrophin expression by systemic delivery in body-wide skeletal muscles of
      dystrophic mdx mice. However, the levels of dystrophin expression vary
      considerably and, more importantly, no dystrophin expression has been achieved in
      cardiac muscle. In this study, we investigate the efficiency of morpholino
      induced exon skipping in cardiomyoblasts and myocytes in vitro, and in cardiac
      muscle in vivo by dose escalation. We showed that morpholino induces targeted
      exon skipping equally effectively in both skeletal muscle myoblasts and
      cardiomyoblasts. Effective exon skipping was achieved in cardiomyocytes in
      culture. In the mdx mice, morpholino rescues dystrophin expression dose
      dependently in both skeletal and cardiac muscles. Therapeutic levels of
      dystrophin were achieved in cardiac muscle albeit at higher doses than in
      skeletal muscles. Up to 50 and 30% normal levels of dystrophin were induced by
      single systemic delivery of 3 g kg(-1) of morpholino in skeletal and cardiac
      muscles, respectively. High doses of morpholino treatment reduced the serum
      levels of creatine kinase without clear toxicity. These findings suggest that
      effective rescue of dystrophin in cardiac muscles can be achieved by morpholino
      for the treatment of Duchenne muscular dystrophy.

PMID- 19759563
TI  - A versatile nonviral vector system for tetracycline-dependent one-step
      conditional induction of transgene expression.
AB  - In this study, we describe a novel self-contained, nonviral vector system for the
      rapid development of tetracycline (Tet)-inducible transgene expression systems in
      mammalian cell lines. To avoid multiple rounds of clonal selection for the
      establishment of stably transfected cell clones, as is necessary with
      conventional systems, we constructed a multicomplementary DNA(cDNA) expression
      vector that enables both one-step targeted genomic integration and conditional
      induction of transgene expression. This vector system consists of several modules
      including a Tet-inducible promoter directing the expression of a transgene and
      two Tet repressor expression units placed in tandem on a single vector. The cell
      clones, generated using a one-step phiC31 integrase-mediated chromosomal
      integration of the multi-cDNA expression construct, showed a stable and robust
      expression with high induction rates upon addition of doxycycline inducer in five
      different cell lines tested. By using this system, we show c-Src-induced cell
      transformation and anticancer cell therapy for this transformation in cultured
      fibroblast cells. The results show a rapid production and accumulation of target
      protein on addition of the inducer starting from extremely low background levels
      and reduction to background levels in a matter of days after the inducer was
      withdrawn from the culture medium.

PMID- 19759564
TI  - The impact of antigen expression in antigen-presenting cells on humoral immune
      responses against the transgene product.
AB  - Treatment of genetic diseases by gene therapy is hampered by immune responses
      against the transgene product. Promoter choice has been shown to be an important
      parameter of the presence or absence of antibodies against the transgene product
      after gene transfer. Here, the generality of some of these observations was
      tested by comparing different murine strains and different transgene products. We
      show immunological unresponsiveness for human apolipoprotein (apo) A-I in six
      murine strains after transfer with E1E3E4-deleted adenoviral vectors containing
      hepatocyte-specific expression cassettes. However, differences in the induction
      of a humoral immune response against human apo A-I after gene transfer with
      vectors driven by the major histocompatibility complex class II Ebeta promoter
      and the ubiquitously active cytomegalovirus promoter were not consistent in these
      six murine strains. Furthermore, use of a potent hepatocyte-specific expression
      cassette did not prevent a humoral immune response against human plasminogen in
      C57BL/6 mice. In contrast, human microplasminogen transfer resulted in stable
      expression in the absence of an immune response against the transgene product.
      Taken together, the molecular design of strategies to abrogate or induce an
      immune response against the transgene product may be hampered by the multitude of
      parameters affecting the outcome, thus limiting the external validity of results.

PMID- 19759565
TI  - A vaccine that delivers rather than induces antibodies.

PMID- 19759566
TI  - AAV5-mediated gene transfer to the parotid glands of non-human primates.
AB  - Salivary glands are potentially useful target sites for multiple clinical
      applications of gene transfer. Previously, we have shown that serotype 2 adeno
      associated viral (AAV2) vectors lead to stable gene transfer in the parotid
      glands of rhesus macaques. As AAV5 vectors result in considerably greater
      transgene expression in murine salivary glands than do AAV2 vectors, herein we
      have examined the use of AAV5 vectors in macaques at two different doses (n = 3
      per group; 10(10) or 3 x 10(11) particles per gland). AAV5 vector delivery, as
      with AAV2 vectors, led to no untoward clinical, hematological or serum chemistry
      responses in macaques. The extent of AAV5-mediated expression of rhesus
      erythropoietin (RhEpo) was dose-dependent and similar to that seen with an AAV2
      vector. However, unlike results with the AAV2 vector, AAV5 vector-mediated RhEpo
      expression was transient. Maximal expression peaked at day 56, was reduced by
      approximately 80% on day 84 and thereafter remained near background levels until
      day 182 (end of experiment). Quantitative PCR studies of high-dose vector
      biodistribution at this last time point showed much lower AAV5 copy numbers in
      the targeted parotid gland (approximately 1.7%) than found with the same AAV2
      vector dose. Molecular analysis of the conformation of vector DNA indicated a
      markedly lower level of concatamerization for the AAV5 vector compared with that
      of a similar AAV2 vector. In addition, cellular immunological studies suggest
      that host response differences may occur with AAV2 and AAV5 vector delivery at
      this mucosal site. The aggregate data indicate that results with AAV5 vectors in
      murine salivary glands apparently do not extend to macaque glands.

PMID- 19759567
TI  - Partial protection against SIV challenge by vaccination of adenovirus and MVA
      vectors in rhesus monkeys.
AB  - This study explores the effect of priming rhesus monkeys with an Ad5/35 vector
      expressing simian immunodeficiency virus (SIV) gag and gp120, and then boosting
      the animals with an modified vaccinia virus Ankara (MVA) vector encoding the same
      antigens after a 2-month interval. The animals were intravenously challenged with
      100 TCID50 of highly pathogenic SIVmac239 virus 2 months after the booster
      vaccination. The priming vaccination induced robust SIV-specific cell-mediated
      and humoral immune responses, and boosting further enhanced the cellular
      immunity. Vaccination reduced peak and long-term viral loads by 1-2 logs for a
      period of >6 months, as reflected by a reduction in both the SIV RNA and DNA
      levels. Of considerable interest, the immunized monkeys did not suffer from loss
      of CD4 T cells, particularly central memory CD4 T cells. These results
      demonstrate that prophylactic vaccination with Ad5/35 followed by MVA reduces
      viral replication and prevents CD4 T-cell loss, and that these effects may
      decrease the likelihood of disease progression.

PMID- 19759573
TI  - Taking the NICE path.

PMID- 19759568
TI  - VEGFR1-activity-independent metastasis formation.
AB  - Molecules such as vascular endothelial growth factor (VEGF) or placental growth
      factor-critical regulators of tumour angiogenesis-are also thought to mobilize
      into blood circulation bone marrow-derived cells (BMDCs), which may subsequently
      be recruited to tumours and facilitate tumour growth and metastasis. A study has
      suggested that BMDCs form 'metastatic niches' in lungs before arrival of cancer
      cells, and showed that pharmacological inhibition of VEGF receptor 1 (VEGFR1,
      also known as Flt1)-cognate receptor for VEGF and placental growth factor
      prevented BMDC infiltration in lungs and 'metastatic niche' formation. Here we
      report that blockade of VEGFR1 activity does not affect the rate of spontaneous
      metastasis formation in a clinically relevant and widely used preclinical model.
      Therefore, alternative pathways probably mediate the priming of tissues for
      metastasis.

PMID- 19759574
TI  - Trust, but verify.

PMID- 19759575
TI  - SETI at 50.

PMID- 19759583
TI  - Journal club. A coastal ecologist sees the hidden effects of hurricanes.

PMID- 19759588
TI  - Vaccine venture boosts health hopes.

PMID- 19759589
TI  - Ear to the Universe starts listening.

PMID- 19759590
TI  - Ghosts still present in the medical machine.

PMID- 19759591
TI  - Choon Fong Shih. Interviewed by Daniel Cressey.

PMID- 19759592
TI  - Wonder weed plans fail to flourish.

PMID- 19759593
TI  - Money in biomedicine: The senator's sleuth.

PMID- 19759594
TI  - Health economics: Life in the balance.

PMID- 19759595
TI  - Keeping track of the Earth's carbon-cycle components.

PMID- 19759596
TI  - Don't overlook the rigorously reviewed novel work in patents.

PMID- 19759597
TI  - Non-lethal weapons and the civilian death toll in war time.

PMID- 19759598
TI  - The need for a fresh symbol to designate copernicium.

PMID- 19759599
TI  - Were crocodiles responsible for the stones we call tools?

PMID- 19759600
TI  - Ethical concerns over use of new cloning technique in humans.

PMID- 19759601
TI  - Plan B for Copenhagen.

PMID- 19759602
TI  - An alien concept.

PMID- 19759603
TI  - Ocean fertilization: time to move on.

PMID- 19759606
TI  - Q&A: The inventor with an ear for the past. Interview by Jascha Hoffman.

PMID- 19759607
TI  - Atmospheric chemistry: Thwarting the seeds of clouds.

PMID- 19759608
TI  - Developmental biology: Asexual healing.

PMID- 19759610
TI  - Fluid dynamics: To merge or not to merge ...

PMID- 19759611
TI  - Genomics: Hepatitis C virus gets personal.

PMID- 19759612
TI  - Biological chemistry: Beyond radical thinking.

PMID- 19759613
TI  - Epigenetics: Ready for the marks.

PMID- 19759614
TI  - Microbiology: Showering with bacteria.

PMID- 19759615
TI  - Misaligned spin and orbital axes cause the anomalous precession of DI Herculis.
AB  - The orbits of binary stars precess as a result of general relativistic effects,
      forces arising from the asphericity of the stars, and forces from any additional
      stars or planets in the system. For most binaries, the theoretical and observed
      precession rates are in agreement. One system, however-DI Herculis-has resisted
      explanation for 30 years. The observed precession rate is a factor of four slower
      than the theoretical rate, a disagreement that once was interpreted as evidence
      for a failure of general relativity. Among the contemporary explanations are the
      existence of a circumbinary planet and a large tilt of the stellar spin axes with
      respect to the orbit. Here we report that both stars of DI Herculis rotate with
      their spin axes nearly perpendicular to the orbital axis (contrary to the usual
      assumption for close binary stars). The rotationally induced stellar oblateness
      causes precession in the direction opposite to that of relativistic precession,
      thereby reconciling the theoretical and observed rates.

PMID- 19759616
TI  - Non-coalescence of oppositely charged drops.
AB  - Electric fields induce motion in many fluid systems, including polymer melts,
      surfactant micelles and colloidal suspensions. Likewise, electric fields can be
      used to move liquid drops. Electrically induced droplet motion manifests itself
      in processes as diverse as storm cloud formation, commercial ink-jet printing,
      petroleum and vegetable oil dehydration, electrospray ionization for use in mass
      spectrometry, electrowetting and lab-on-a-chip manipulations. An important issue
      in practical applications is the tendency for adjacent drops to coalesce, and
      oppositely charged drops have long been assumed to experience an attractive force
      that favours their coalescence. Here we report the existence of a critical field
      strength above which oppositely charged drops do not coalesce. We observe that
      appropriately positioned and oppositely charged drops migrate towards one another
      in an applied electric field; but whereas the drops coalesce as expected at low
      field strengths, they are repelled from one another after contact at higher field
      strengths. Qualitatively, the drops appear to 'bounce' off one another. We
      directly image the transient formation of a meniscus bridge between the bouncing
      drops, and propose that this temporary bridge is unstable with respect to
      capillary pressure when it forms in an electric field exceeding a critical
      strength. The observation of oppositely charged drops bouncing rather than
      coalescing in strong electric fields should affect our understanding of any
      process involving charged liquid drops, including de-emulsification, electrospray
      ionization and atmospheric conduction.

PMID- 19759617
TI  - New particle formation in forests inhibited by isoprene emissions.
AB  - It has been suggested that volatile organic compounds (VOCs) are involved in
      organic aerosol formation, which in turn affects radiative forcing and climate.
      The most abundant VOCs emitted by terrestrial vegetation are isoprene and its
      derivatives, such as monoterpenes and sesquiterpenes. New particle formation in
      boreal regions is related to monoterpene emissions and causes an estimated
      negative radiative forcing of about -0.2 to -0.9 W m(-2). The annual variation in
      aerosol growth rates during particle nucleation events correlates with the
      seasonality of monoterpene emissions of the local vegetation, with a maximum
      during summer. The frequency of nucleation events peaks, however, in spring and
      autumn. Here we present evidence from simulation experiments conducted in a plant
      chamber that isoprene can significantly inhibit new particle formation. The
      process leading to the observed decrease in particle number concentration is
      linked to the high reactivity of isoprene with the hydroxyl radical (OH). The
      suppression is stronger with higher concentrations of isoprene, but with little
      dependence on the specific VOC mixture emitted by trees. A parameterization of
      the observed suppression factor as a function of isoprene concentration suggests
      that the number of new particles produced depends on the OH concentration and
      VOCs involved in the production of new particles undergo three to four steps of
      oxidation by OH. Our measurements simulate conditions that are typical for
      forested regions and may explain the observed seasonality in the frequency of
      aerosol nucleation events, with a lower number of nucleation events during summer
      compared to autumn and spring. Biogenic emissions of isoprene are controlled by
      temperature and light, and if the relative isoprene abundance of biogenic VOC
      emissions increases in response to climate change or land use change, the new
      particle formation potential may decrease, thus damping the aerosol negative
      radiative forcing effect.

PMID- 19759618
TI  - Holocene thinning of the Greenland ice sheet.
AB  - On entering an era of global warming, the stability of the Greenland ice sheet
      (GIS) is an important concern, especially in the light of new evidence of rapidly
      changing flow and melt conditions at the GIS margins. Studying the response of
      the GIS to past climatic change may help to advance our understanding of GIS
      dynamics. The previous interpretation of evidence from stable isotopes
      (delta(18)O) in water from GIS ice cores was that Holocene climate variability on
      the GIS differed spatially and that a consistent Holocene climate optimum-the
      unusually warm period from about 9,000 to 6,000 years ago found in many northern
      latitude palaeoclimate records-did not exist. Here we extract both the Greenland
      Holocene temperature history and the evolution of GIS surface elevation at four
      GIS locations. We achieve this by comparing delta(18)O from GIS ice cores with
      delta(18)O from ice cores from small marginal icecaps. Contrary to the earlier
      interpretation of delta(18)O evidence from ice cores, our new temperature history
      reveals a pronounced Holocene climatic optimum in Greenland coinciding with
      maximum thinning near the GIS margins. Our delta(18)O-based results are
      corroborated by the air content of ice cores, a proxy for surface elevation.
      State-of-the-art ice sheet models are generally found to be underestimating the
      extent and changes in GIS elevation and area; our findings may help to improve
      the ability of models to reproduce the GIS response to Holocene climate.

PMID- 19759619
TI  - Genotypic sex determination enabled adaptive radiations of extinct marine
      reptiles.
AB  - Adaptive radiations often follow the evolution of key traits, such as the origin
      of the amniotic egg and the subsequent radiation of terrestrial vertebrates. The
      mechanism by which a species determines the sex of its offspring has been linked
      to critical ecological and life-history traits but not to major adaptive
      radiations, in part because sex-determining mechanisms do not fossilize. Here we
      establish a previously unknown coevolutionary relationship in 94 amniote species
      between sex-determining mechanism and whether a species bears live young or lays
      eggs. We use that relationship to predict the sex-determining mechanism in three
      independent lineages of extinct Mesozoic marine reptiles (mosasaurs,
      sauropterygians and ichthyosaurs), each of which is known from fossils to have
      evolved live birth. Our results indicate that each lineage evolved genotypic sex
      determination before acquiring live birth. This enabled their pelagic radiations,
      where the relatively stable temperatures of the open ocean constrain temperature
      dependent sex determination in amniote species. Freed from the need to move and
      nest on land, extreme physical adaptations to a pelagic lifestyle evolved in each
      group, such as the fluked tails, dorsal fins and wing-shaped limbs of
      ichthyosaurs. With the inclusion of ichthyosaurs, mosasaurs and sauropterygians,
      genotypic sex determination is present in all known fully pelagic amniote groups
      (sea snakes, sirenians and cetaceans), suggesting that this mode of sex
      determination and the subsequent evolution of live birth are key traits required
      for marine adaptive radiations in amniote lineages.

PMID- 19759622
TI  - Deconvolution of spatial-correlation spectra for high-resolution astronomical
      imaging.
AB  - A number of techniques used for high-resolution speckle imaging in astronomy
      generate average spatial-correlation spectra of objects. Here a straightforward
      method for iteratively deconvolving these noisy spectra to obtain high-resolution
      images is described.

PMID- 19759623
TI  - Phase-only entropy-optimized filter generated by simulated annealing.
AB  - Highly selective and efficient optical pattern recognition is implemented by
      using phase-only entropy-optimized filters generated by simulated annealing. An
      electro-optic architecture is proposed for filter generation.

PMID- 19759620
TI  - Optogenetic dissection of a behavioural module in the vertebrate spinal cord.
AB  - Locomotion relies on neural networks called central pattern generators (CPGs)
      that generate periodic motor commands for rhythmic movements. In vertebrates, the
      excitatory synaptic drive for inducing the spinal CPG can originate from either
      supraspinal glutamatergic inputs or from within the spinal cord. Here we identify
      a spinal input to the CPG that drives spontaneous locomotion using a combination
      of intersectional gene expression and optogenetics in zebrafish larvae. The photo
      stimulation of one specific cell type was sufficient to induce a symmetrical tail
      beating sequence that mimics spontaneous slow forward swimming. This neuron is
      the Kolmer-Agduhr cell, which extends cilia into the central cerebrospinal-fluid
      containing canal of the spinal cord and has an ipsilateral ascending axon that
      terminates in a series of consecutive segments. Genetically silencing Kolmer
      Agduhr cells reduced the frequency of spontaneous free swimming, indicating that
      activity of Kolmer-Agduhr cells provides necessary tone for spontaneous forward
      swimming. Kolmer-Agduhr cells have been known for over 75 years, but their
      function has been mysterious. Our results reveal that during early development in
      zebrafish these cells provide a positive drive to the spinal CPG for spontaneous
      locomotion.

PMID- 19759624
TI  - Phase measurement of a Fourier spectrum by a fringe-scanning phase-conjugate
      interferometer.
AB  - We present a novel method for obtaining the phase distribution of an object
      spectrum by using a fringe-scanning phase-conjugate interferometer. A detailed
      analysis of the proposed technique is provided, and experimental demonstrations
      for validating this technique are also given. The major advantages of this method
      are its potentially high accuracy and its low space-bandwidth-product requirement
      for the detection system.

PMID- 19759625
TI  - Two-wavelength photorefractive dynamic optical interconnect.
AB  - A novel architecture for a reconfigurable optical routing switch using
      photorefractive crystals with nondestructive readout is presented. This design
      reduces the order of complexity from n(2) to n for a general two-wavelength n x n
      holographic interconnection network. The packing capacity of the network is
      discussed and is calculated to be of the order of 1000 x 1000 for an ideal volume
      holographic recording material. In practice, we show that the actual value is
      constrained by the number of gratings that can be multiplexed in a single
      photorefractive crystal. A 2 x 3 switch is demonstrated by using a Bi(12)GeO(20)
      crystal with 514-nm writing beams and 633-nm signal (readout) beams.

PMID- 19759626
TI  - Acousto-optic photonic switch.
AB  - An acousto-optic architecture is presented to implement a nonblocking space
      division switch with O(N) complexity. Signal degradation is minimal so that the
      switch is suitable for nonregenerative application within optical networks; it is
      also capable of rapid reconfiguration. Experiments for a 1 x 4 switch show an
      insertion loss ranging from 4.6 to 5.6 dB, a worst-case signal-to-cross-talk
      ratio of better than 30 dB, and a reconfiguration time of 1.46 microsec.

PMID- 19759627
TI  - Wideband temperature-compensated optical isolator or circulator configuration
      using two Faraday elements.
AB  - Two Faraday elements are configured with two linear retardation elements such
      that the variations in their individual rotations due to wavelength and
      temperature changes are compensated for. Wideband isolation between 1250 and 1650
      nm is demonstrated using 45 degrees and 90 degrees yttrium iron garnet elements
      and two 45 degrees right-angle glass prisms (n ~ 1.73) that produce approximately
      60 degrees linear retardations on total internal reflection.

PMID- 19759628
TI  - Comparison of surface scattering between identical, randomly rough metal and
      dielectric diffusers.
AB  - A method of replicating randomly rough surfaces fabricated in photoresist has
      been developed, enabling comparisons of the scattered light to be made between
      identical diffusers made from different materials. Experimental measurements on
      one-dimensional metal (gold) and dielectric surfaces are presented, and some
      initial comparisons with numerical calculations are made.

PMID- 19759629
TI  - Uncertainty-limited position measurement of moving atoms using optical fields.
AB  - A method for measuring atomic spatial distributions is suggested, based on Raman
      transitions in an applied force field. This technique eliminates the Doppler
      effect and provides high-frequency resolution for long-lived states, leading to
      position resolution that is fundamentally limited by the uncertainty principle.
      The effects of atomic motion are discussed, and a simplified analysis of the
      method is presented.

PMID- 19759630
TI  - Injection locking of a 13-W cw Nd:YAG ring laser.
AB  - A lamp-pumped, 13-W cw Nd:YAG ring laser at 1.064 microm is injection locked
      using a 40-mW single-frequency diodelaser-pumped Nd:YAG laser as the master
      oscillator. The phase fidelity of the injected slave to the master is measured
      using an all-optical technique.

PMID- 19759631
TI  - Coupled-cavity mode locking of a KCl:Tl laser using an erbium-doped optical
      fiber.
AB  - An erbium-doped monomode fiber that exhibits enhanced optical nonlinearity has
      been incorporated into a coupled-cavity mode-locked (CCM) KCl:Tl laser, from
      which stable, sub-100-fsec pulses have been produced near 1.5 microm. Spectral
      measurements of the CCM laser output also indicate the existence of a self
      frequency shift that can provide pulse generation in two distinct wavelength
      regimes.

PMID- 19759632
TI  - Synchronously pumped, femtosecond dye laser insensitive to cavity-length
      variations of up to 15 microm.
AB  - A synchronously pumped, hybridly mode-locked, antiresonant-ring dye laser that is
      insensitive to cavity-length variations of up to 15 microm is described. At a
      cavity length that is 70-80 microm shorter than the synchronous cavity length
      this laser generates stable pulses as short as 55 fsec, with a pulse width of 65
      fsec being typical (assuming a sech(2) pulse shape). No evidence for colliding
      pulse mode-locking effects is observed.

PMID- 19759633
TI  - Two-beam coupling with a photoconductor-thermoplastic device.
AB  - Two-beam coupling of coherent optical beams using a photoconductor-thermoplastic
      device is discussed. Calculations of the optical gain as a function of various
      recording parameters are presented. A method to control the relative phase
      between the interference pattern of the recording beams to the resulting surface
      deformation is described. Experimental results demonstrate that a gain factor of
      close to 5 can be achieved.

PMID- 19759634
TI  - Second-harmonic diffraction from a monolayer grating.
AB  - Diffracted surface second-harmonic radiation emerging in several orders has been
      observed from a periodically modulated monolayer of adsorbed dye molecules. The
      molecular grating was produced by laser-induced desorption in the field of two
      crossed beams. An elementary theory is presented that relates the characteristics
      of the second-harmonic diffraction pattern to the spatially varying properties of
      the surface and is applied to infer the adsorbate density profile of the
      spatially modulated grating. The density profile is compared with the predictions
      of a model of grating formation based on thermal desorption.

PMID- 19759635
TI  - Index-of-refraction change in optically pumped solid-state laser materials.
AB  - Degenerate four-wave mixing measurements were made on several Nd(3+)-doped laser
      materials by resonantly pumping the Nd(3+) ions. The dominant contribution to the
      signal under these conditions is associated with the difference in
      polarizabilities of the Nd(3+) ions in the metastable state versus the ground
      state. Absolute measurements of the signal strengths imply a laser-induced
      polarizability change of the order of 0.01-0.05 A(3). The results indicate that,
      for the case of a single-shot laser amplifier system, the beam distortion induced
      by this population induced change in the refractive index is comparable with the
      distortion arising from thermal effects.

PMID- 19759636
TI  - Intensity-dependent loss properties of window materials at 248 nm.
AB  - Transmission of fused silica, CaF(2), LiF, and MgF(2) is measured using 450-fsec,
      248-nm pulses in the range 10-120 GW/cm(2). Different loss mechanisms such as
      scattering of transmitted radiation, color-center formation, and multiphoton
      absorption were studied separately. For fused silica a two-photon absorption
      mechanism is found, while for CaF(2), LiF, and MgF(2) three-photon absorption and
      absorption due to color-center formation are found as dominant absorption
      mechanisms.

PMID- 19759637
TI  - Adaptive fringe-locked running hologram in photorefractive crystals.
AB  - We have recorded running holograms in a photorefractive crystal with an applied
      electric field, using a 90 degrees phase-shift fringe-locked interference pattern
      of light. This method provides a simple way to obtain optimal conditions for
      nonstationary holographic recording. The experiment that we describe allows us to
      calculate the crystal diffusion length L(D) and provides direct evidence of the
      occurrence of running holograms in photorefractive crystals. Experimental results
      for a Bi(12)SiO(20) sample are reported.

PMID- 19759638
TI  - Instabilities and self-pulsation in a ring cavity with a photorefractive wave
      mixer.
AB  - We find instabilities and self-pulsation in an optical ring cavity with a
      photorefractive two-wave mixer. The mean field limit is used to obtain a single
      criterion for instabilities that originate from a Hopf bifurcation.

PMID- 19759639
TI  - Raman cross talk of soliton collision in a lossless fiber.
AB  - The cross talk induced by soliton collision with a Raman effect in a lossless
      fiber is discussed. There are frequency-shift enhancements for the two colliding
      solitons in addition to the energy transfer. The maximum rate-distance product
      limited by energy depletion is obtained for the soliton-based wavelength-division
      multiplexing system.

PMID- 19759640
TI  - Resistance of solitons to the effects of polarization dispersion in optical
      fibers.
AB  - Using numerical simulation, we show that solitons of any pulse width can avoid
      splitting or excessive broadening in response to birefringence of randomly
      varying orientation as long as the fiber's polarization-dispersion parameter (in
      psec/km((1/2))) is less than ~0.3D((1/2)), where D is the dispersion parameter
      (in psec nm(-1) Km(-1)). Nevertheless, we also find that polarization dispersion
      tends to produce a significant amount of dispersive wave radiation from the
      soliton.

PMID- 19759641
TI  - Coupled-mode formulations.
AB  - Vector coupled-mode theory is extended beyond the conventional first-order
      treatment. Good results are obtained from the extended theory in the case of
      waveguides with large index discontinuity.

PMID- 19759642
TI  - Optical-fiber Fabry-Perot embedded sensor.
AB  - A reflectively monitored optical-fiber Fabry-Perot interferometer was embedded in
      a graphite-epoxy composite material. Its performance as a temperature sensor was
      demonstrated from 20 to 200 degrees C. The change in relative phase shift with
      temperature, Deltao/oDeltaT, was measured to be 8.0 x 10(-6)/ degrees C for this
      embedded sensor. This value is 4% lower than for one employing a similar fiber in
      an air ambient. A thermal expansion coefficient for the composite material in the
      direction of the fiber axis is estimated from these data to be 2.1 x 10(-7)/
      degrees C.

PMID- 19759643
TI  - Polarization multiplexing applied to a fiber current sensor.
AB  - The measurement of Faraday rotation can be made insensitive to linear
      birefringence by time multiplexing of different states of polarization at the
      input of the fiber. This offers a new possibility of overcoming the linear
      birefringence effect in fiber current sensors. Experimental results and the
      measurement accuracy versus the quality of the optical components used are
      presented.

PMID- 19759644
TI  - Radiation loss in bent step-index slab waveguides.
AB  - Based on the exact scalar wave equations of bent slab waveguides, locally leaky
      mode attenuation constants for both TE and TM modes are derived by using the WKB
      tunneling theory. Changes in propagation constant due to waveguide bending are
      considered in our calculation. Under some assumptions, our results are found to
      be identical to other results obtained using entirely different methods.

PMID- 19759645
TI  - Phase-matched electromagnetic scattering in active dielectric films.
AB  - An investigation of oblique plane-wave electromagnetic scattering from active
      dielectric films reveals the existence of anomalously large resonances that occur
      at discrete plane-wave angles of incidence. These resonances may be understood
      from a leaky-wave phase-matching condition whose predictions for the first few
      modes agree to within a few percent of those obtained from a rigorous treatment
      using Maxwell's equations. Enhancement in the scattered-field intensities of the
      order of 100 was observed in experiments using finite-diameter pump and probe
      laser beams and active films as thin as 6 microm.

PMID- 19759646
TI  - Chaos in a conventional nonlinear coupler.
AB  - Conventional optical-fiber directional couplers composed of isotropic material
      can exhibit chaotic power splitting when the input polarization is inclined to
      the geometric axes of coupler.

PMID- 19759647
TI  - Integrated-optic acoustically tunable reflection filter.
AB  - We demonstrate a two-stage, integrated-optic, acoustically tunable filter formed
      by reflecting the output of a single stage acousto-optic filter back through the
      filter by means of an integral mirror. Relative to a single-stage device, this
      double-pass configuration provides greatly improved sidelobe suppression (to
      approximately -20 dB) and a 72% reduction in filter bandwidth (to less than 0.9
      nm at a wavelength of 1.52 microm). The performance of this device is shown to be
      equal to the far more difficult to fabricate cascaded pair of strictly matched
      acousto-optic filters.

PMID- 19759648
TI  - Ferroelectric liquid-crystal tunable filter.
AB  - A new discrete-channel tunable Lyot filter that uses ferroelectric liquid-crystal
      (FLC) smectic C* wave plates is described and demonstrated. The device is tuned
      by changing the retardation of each birefringent element. This is achieved by
      electrically rotating the FLC wave plates in each stage by 45 degrees , which
      effectively changes the design wavelength of the Lyot filter. The transmission
      characteristics of such a device are demonstrated in a three-stage filter and
      show good agreement with theory. Advantages of the FLC tunable filter over
      existing filter structures include low switching voltages (+/-10 V), rapid
      tunability (~100 kHz), potentially high transmission and wide field of view, and
      large entrance aperture.

PMID- 19759649
TI  - Automatic shadow moire topography: a moving-light-source method.
AB  - A method for automatically determining in real time the absolute order of shadow
      moire fringes is developed. The intensity variations on an object surface caused
      by a light source moving with constant speed are analyzed by fast-Fourier
      transform methods. Experimental results show that this procedure can be
      successfully applied to shadow moire topography and does not require object
      surface continuity.

PMID- 19759650
TI  - Content-addressable-memory-based single-stage optical modified-signed-digit
      arithmetic.
AB  - Using a novel nonholographic optoelectronic content-addressable memory in a free
      space angular multiplexing geometry, a single-optical-stage compact parallel
      optical modified-signed-digit arithmetic processing architecture is proposed.
      Some spatial light modulator based experimental results are also presented.

PMID- 19759651
TI  - Ultrafast all-optical logic gates based on soliton trapping in fibers.
AB  - Ultrafast all-optical soliton-trapping logic gates, including an inverter,
      exclusive OR, and AND, are experimentally demonstrated in birefringent fibers.
      The soliton-trapping logic gates are three terminal devices with orthogonally
      polarized inputs, phase-insensitive nonlinear operation, and switching energies
      of ~42 pJ. Using a 0.2-THz bandpass filter, the contrast ratio for the exclusive
      OR gate is ~8:1, but the output pulses are ~10 times broader than the input pulse
      width. By widening the filter bandpass to 0.58 THz, an inverter is demonstrated
      with an ~4:1 contrast ratio and output pulses that can propagate as solitons in a
      fiber. Numerical simulations show that the output from the inverter can be
      cascaded to other trapping gates.

PMID- 19759652
TI  - Investigation of the infrared properties of ZnS:diamond composites.
AB  - A tough, IR, transparent dielectric has been fabricated from a sintered
      ZnS:diamond composite. Far-IR reflectivity measurements of the reststrahlen band
      with volume fill fractions as large as 33% diamond give results consistent with
      the predictions of the effective medium approximation.

PMID- 19759653
TI  - Variation of the temporal delay to threshold in nanosecond-tunable dye lasers.
AB  - We present an experimental study, complemented by numerical simulations, of the
      delay from the peak of the pump pulse to threshold of the dye laser pulse as a
      function of the selected wavelength. Delay variations of up to 0.2 nsec/nm were
      observed in Rhodamine dyes pumped by a N(2) laser. We conclude that the
      variations are intrinsic to the gain-loss characteristics and that excited-state
      singlet absorption can play a significant role.

PMID- 19759654
TI  - Efficient erbium-doped fiber amplifier at a 1.53-microm wavelength with a high
      output saturation power.
AB  - An efficient erbium-doped fiber amplifier providing gains from +25 to +37 dB with
      pump powers at lambda = 1.49 microm in the 11-54-mW range is described.
      Corresponding saturation output powers of +2.5 to +11 dBm were achieved. A
      maximum gain coefficient of 2.1 +/- 0.1 dB/mW was measured, which is to our
      knowledge the highest value reported for erbium-doped fiber amplifiers pumped
      near lambda = 1.49 microm and matches previously reported results for a lambda =
      980-nm pump.

PMID- 19759655
TI  - Mode-locked erbium-doped fiber laser with soliton pulse shaping.
AB  - We have generated pulses as short as 4 psec at 1530 nm from a mode-locked erbium
      doped fiber laser. The mode locker is a wide-bandwidth, lithium niobate guided
      wave modulator, and the fiber laser is completely integrated. We present evidence
      that soliton pulse shaping is playing a key role in the formation of the pulses.

PMID- 19759656
TI  - 64-dB amplification of 19-psec laser-diode pulses in a Ti-sapphire laser.
AB  - We report 64-dB amplification of 19.4-psec pulses at 820 nm at a 2-kHz repetition
      rate in an injection-seeded Ti:Al(2)O(3) laser oscillator. In a single-pass
      amplifier configuration, a 5.2-dB gain was measured. We discuss the advantages of
      the short-pulse injection-seeding technique as a means of constructing an all
      solid-state tunable source of picosecond and subpicosecond laser pulses in the
      near infrared.

PMID- 19759657
TI  - Noise suppression in photorefractive image amplifiers.
AB  - We propose and experimentally demonstrate a simple technique capable of
      significantly enhancing the signal-to-noise ratio of photorefractive amplifiers.
      The optical noise due to amplified scattered light and multiple interface
      reflections is removed by performing two-wave mixing in off-axis-rotating
      BaTiO(3) and Bi(12)SiO(20) crystals. A 20-fold improvement of the signal-to-noise
      ratio is achieved, and virtually noise-free image amplifiers are demonstrated.

PMID- 19759658
TI  - Optical and photorefractive properties of InP:Ti: a new photorefractive
      semiconductor.
AB  - The optical and photorefractive properties of Ti-doped InP are investigated. Four
      wave mixing at wavelengths of 1.06 and 1.32 microm has been observed for the
      first time to our knowledge in semi-insulating InP:Ti. Room-temperature
      diffraction efficiencies for zero applied bias are larger than efficiencies
      measured previously for InP:Fe because of the absence of bipolar
      photoconductivity. Photoconductivity is observed out to 2 microm, which raises
      the possibility of photorefractive mixing at longer wavelengths than previously
      explored.

PMID- 19759659
TI  - Dark-soliton generation in optical fibers.
AB  - We study the generation of dark-pulse solitons in nonlinear-optical fibers in the
      normal dispersion regime. We demonstrate that dark solitons may be created as
      pairs by an arbitrary dark pulse without a threshold and obtain the parameters of
      the generated solitons. The cases of soliton creation by a boxlike dark pulse and
      a random Gaussian pulse are also described.

PMID- 19759660
TI  - Experimental observation of soliton interaction over long fiber paths: discovery
      of a long-range interaction.
AB  - We have studied the interaction of ~55-psec-duration soliton pulse pairs over
      thousands of kilometers of optical fiber with loss periodically compensated by
      Raman gain. We indeed observe the expected short-range, phase-dependent
      interaction. But we also observe a long-range, phase-independent interaction
      caused by dispersive-wave radiation from the solitons.

PMID- 19759661
TI  - Universal dynamic phase-calibration technique for fiber-optic interferometric
      sensors and phase modulators.
AB  - A new technique for dynamic phase calibration that utilizes only visual
      observation of the fringe pattern is demonstrated for use in fiber-optic
      interferometric sensors and phase modulators. The need for a photodetector and
      its associated electronic circuitry is completely eliminated. Observations show
      that random changes in phase, source intensity, and fringe visibility do not
      affect the phase calibration. Since no phase bias or feedback is necessary, the
      new method is simple and fast. This technique is of universal applicability to
      any two-beam interferometer incorporating dynamic sinusoidal displacements.

PMID- 19759662
TI  - Dispersion-related multimode instabilities and self-sustained oscillations in
      nonlinear counterpropagating waves: erratum.

PMID- 19759663
TI  - Achromatic volume holography using dispersive compensation for grating tilt.
AB  - A method for achromatic volume holography is described using a combination of
      material and grating dispersion. With barium titanate as the dispersive material,
      a bandwidth of 250 nm is realized. The device may be used for broadband phase
      conjugation and image reconstruction.

PMID- 19759664
TI  - Maximum fractional energy transmissible over a linear dispersive medium.
AB  - We investigate the problem of transmitting the maximum fractional energy over a
      given length of a linear dispersive medium (e.g., a single-mode optical fiber)
      once the input pulse duration and the output detection time are assigned.

PMID- 19759665
TI  - Holographic implementation of a learning machine based on a multicategory
      perceptron algorithm.
AB  - An optical learning machine that has multicategory classification capability is
      demonstrated. The system exactly implements the single-layer perceptron algorithm
      and is fully parallel and analog. Experimental results on the learning by
      examples obtained from the system are described.

PMID- 19759666
TI  - Tunable-diode-laser frequency-modulation spectroscopy using balanced homodyne
      detection.
AB  - Quantum-limited frequency-modulation spectroscopy (FMS) has been performed with
      tunable diode lasers at 5.4 and 1.3 microm by employing a dual-beam balanced
      homodyne detection scheme to suppress optical fringes, residual amplitude
      modulation, and excess laser noise by 15-20 dB. Performing FMS at the two
      wavelengths involved different lasers (lead salt and InGaAsP, respectively),
      optics, and detectors, which emphasizes the versatility and applicability of the
      technique. System sensitivities of 1 x 10(-7) and 2 x 10(-7) were obtained for
      the respective systems.

PMID- 19759667
TI  - Off-axis folded laser beam trajectories in a strip-line CO(2) laser.
AB  - Using an rf-excited strip-line CO(2) laser with large lateral dimensions (a high
      Fresnel number) in a hemiconfocal optical cavity configuration, we observe modes
      that are distinctively off axial. They can be viewed as folded Gaussian beams
      with trajectories in the shapes of the letters M and W. Either of these modes can
      be isolated by suppressing the other mode through the introduction of a suitably
      positioned obstacle into the cavity. Computer simulations of the radiation
      propagation in the cavity yielded field distributions conforming to the observed
      pattern.

PMID- 19759668
TI  - Lau cavity and phase locking of laser arrays.
AB  - The Lau cavity is the self-imaging cavity with a phase corrector under the Lau
      reimaging condition. I propose the use of the Lau cavity to utilize both the
      Talbot and the Lau effects for phase locking one-dimensional and two-dimensional
      diode-laser arrays into a single-lobe coherent beam. Analyses on the self
      reproducing of a coherent lasing field and the reimaging of initial incoherent
      radiation are given.

PMID- 19759669
TI  - Optically induced reorientational aggregation and the stability of F(2)(+) color
      center lasers.
AB  - Spectroscopic evidence is presented showing that F(2) centers in KCI optically
      convert to an array of higher Faggregate centers at temperatures as low as 40 K.
      This aggregation occurs through random diffusion of F(2)(+) centers by means of
      repeated optical reorientation. Stable lasing of the F(2)(+) center has been
      achieved at a crystal temperature below which this reorientational aggregation
      ceases.

PMID- 19759670
TI  - Gain-switched pulsed operation of microchip lasers.
AB  - Microchip lasers have produced single-frequency, gain-switched pulses with a FWHM
      as short as 760 psec for Nd:YAG (Nd(x)Y(3-x)Al(5)O(12)) and 80 psec for
      LiNdP(4)O(12) (LNP).

PMID- 19759671
TI  - Nonlinear-optical response in polythiophene films using four-wave mixing
      techniques.
AB  - We report measurement of X(3) in polythiophene and a homologous series of
      polycondensed thiophene-based polymers above and below the absorption edge using
      the folded-boxcar four-wave mixing technique. Above gap the nonlinear coefficient
      X(3) was found to be one of the largest and fastest in a polymer.

PMID- 19759672
TI  - Magnetically compensated supersonic beams for nonlinear optics.
AB  - Doppler frequently shifts for a laser field interacting with a diverging
      supersonic atomic beam are canceled using spatially varying Zeeman shifts. Dense
      atomic beams with long interaction path lengths and narrow linewidths are
      obtained for spectroscopic and nonlinear-optics applications.

PMID- 19759673
TI  - Fiber-optic coupling based on nonimaging expanded-beam optics.
AB  - We have fabricated and experimentally tested low-cost and mass-producible
      multimode fiber-optic couplers and connectors based on nonimaging beam-expanding
      optics and Liouville's theorem. Analysis indicates that a pair coupling loss of 
      0.25 dB can be achieved. Experimentally, we measured insertion losses as low as 
      0.38 dB. The beam expanders can be mass produced owing to the use of plastic
      injection-molding fabrication techniques and packaged in standard connector
      housings. This design is compatible with the fiber geometry and can yield highly
      stable coupling owing to its high tolerance for misalignments.

PMID- 19759674
TI  - Quasi-distributed single-length polarimetric sensor.
AB  - A quasi-distributed polarimetric sensor employing a single length of polarization
      preserving fiber is described. The sensing segments are identified by miniature
      rings that squeeze the fiber to couple power from one optical mode to the
      orthogonal mode while avoiding any mechanical damage to the fiber. A
      superluminescent-diode source allows us to exploit the coherent-multiplexing
      concept, which yields high resolution and high precision. Experimental results
      confirm this approach and point toward the development of a quasi-distributed
      sensor with polarimetric sensitivity, high spatial resolution, and fiber-optic
      mechanical integrity.

PMID- 19759675
TI  - Integrated-optic polarization-splitting directional coupler.
AB  - We present a novel integrated-optic polarization-splitting directional coupler
      consisting of two channel waveguides coated with thin layers of metal with
      different thicknesses. Using an effective-index method and a recently developed
      matrix method, we show that such a structure can have extinction ratios of better
      than -20 dB and a loss of less than 1.0 dB.

PMID- 19759676
TI  - High-accuracy picosecond characterization of gain-switched laser diodes.
AB  - A unique combination of the time-correlated photon-counting technique and single
      photon avalanche diode detectors gives an accurate characterization of gain
      switched semiconductor lasers with picosecond resolution. The high sensitivity
      and the clean shape of the time response reveal even small features (reflections
      and relaxation oscillations), making a true optimization of the laser-diode
      operation possible. The technique outperforms the standard characterization with
      ultrafast p-i-n photodiodes and a sampling oscilloscope. In addition, compared
      with other methods, it has favorable features that greatly simplify the
      measurement.

PMID- 19759677
TI  - Lasers without inversion: interference of dressed lifetime-broadened states.
AB  - We describe the use of a coupling electromagnetic field to provide a general
      method of producing inversion-free laser systems. The interference between
      dressed states produces a zero in absorption while allowing gains of the order of
      that of the uncoupled system.

PMID- 19759678
TI  - Amplification of femtosecond pulses in Ti:Al(2)O(3) using an injection-seeded
      laser.
AB  - A 440-fsec, 0.1-pJ pulse from a dye laser is injected into a high-repetition-rate
      Ti:Al(2)O(3) laser pumped by a copper-vapor laser to study the amplification and
      pulse broadening of femtosecond pulses in Ti:Al(2)O(3). Gains of 2 x 10(7) are
      achieved with output pulse durations of 1.1 psec. After recompression with a
      grating pair to compensate dispersion broadening, pulses as short as 275 fsec are
      obtained.

PMID- 19759679
TI  - Enhancement of Stokes conversion by diode-laser injection in a para-H(2) Raman
      laser.
AB  - The injection effect of weak Stokes seed radiation is demonstrated in a para-H(2)
      Raman laser. Injected radiation from a PbSnTe diode laser as low as several
      microwatts resulted in an enhancement of 4 orders of magnitude in the output
      Stokes energy and a reduction in the pumping threshold energy of 22%.
      Characteristics of the injection are investigated as functions of the pumping
      energy, the Stokes seed frequency, and the polarization.

PMID- 19759680
TI  - Self-induced reflection at a saturable interface.
AB  - The reflection properties of an interface between a dielectric and a saturable
      dye solution are investigated. A simple phenomenological approach describes the
      switching behavior, including self-phase-modulation effects induced at the
      interface.

PMID- 19759681
TI  - Polarization-resolved optical phase conjugation in an artificial anisotropic Kerr
      medium.
AB  - Optical phase conjugation by degenerate four-wave mixing has been achieved in a
      liquid suspension of polymer microellipsoids as a result of light-induced
      rotational effects. Different polarization configurations of the pump and probe
      beams have been used, and the resulting conjugate polarization states have been
      discriminated. The results are discussed in terms of different kinds of particle
      orientational gratings.

PMID- 19759682
TI  - Influence of alternating field frequency on enhanced photorefractive gain in two
      beam coupling.
AB  - We derive an analytic expression describing the intensity and field frequency
      dependence of photorefractive gain in two-beam coupling under an alternating
      square-wave electric field. We determine the frequency and intensity ranges over
      which the gain is maximum and time independent. Experimental results for
      Bi(12)GeO(20) crystals are presented.

PMID- 19759683
TI  - Model for resonant intensity dependence of photorefractive two-wave mixing in
      InP:Fe.
AB  - We present a new model, which incorporates both temperature and electron-hole
      effects, for two-beam coupling in photorefractive semiconductors under an
      external dc field E(0). We show that the exponential gain ? exhibits an intensity
      dependent resonance. The application of this model to InP:Fe allows us to predict
      a value of ? near 20 cm(-1) for a thin sample at 1.06 microm with E(0) = 10
      kV/cm.

PMID- 19759684
TI  - Interaction of solitons in tunnel-coupled optical fibers.
AB  - A pair of weakly interacting optical fibers, which are described by two nonlinear
      Schrodinger equations with linear coupling terms, is considered in the framework
      of perturbation theory. It is shown that the interaction of optical solitons in
      this system is inelastic and that they may form a bound state (bisoliton). The
      stability and internal oscillations of the bisoliton are also investigated.

PMID- 19759685
TI  - Continuous-wave-pumped modulational instablity in an optical fiber.
AB  - Continuous-wave-pumped modulational instability in an optical fiber has been
      demonstrated for the first time to our knowledge by using a 5-km single-mode
      fiber that has a small core area and anomalous group-velocity dispersion. This cw
      pumped modulational instability has permitted the generation of a continuous
      optical pulse train with a pulse repetition rate of greater than 100 GHz,
      although stimulated Brillouin scattering occurred along with the modulational
      instability.

PMID- 19759686
TI  - Interactions between dark solitons.
AB  - The interaction forces between two dark solitons are numerically investigated. It
      is found that dark solitons are less affected than bright solitons by their
      respective interaction forces. An empirical expression for the separation of two
      solitons as a function of initial separation and traveling distance is deduced,
      which agrees well with numerical results.

PMID- 19759687
TI  - Polarization coupling power in single-mode single-polarization optical fibers.
AB  - A set of coupled power equations has been derived from a set of coupled amplitude
      equations for a single-mode single-polarization (SMSP) optical fiber. Our results
      indicate that the power coupling coefficients are related not only to the
      birefringence of the SMSP fiber but also to the leaky-mode loss.

PMID- 19759689
TI  - Quadrature phase detector using two-mode waveguides.
AB  - We present a novel design for quadrature phase detection utilizing two-mode
      optical waveguides for optical interferometric systems. A pair of interferometric
      signals having quadrature optical phase information can be obtained from the near
      field and far-field patterns of a two-mode waveguide output. The operational
      principle is based on a pi/2 differential phase shift between two modal beams
      occurring during their transition from near-field to far-field radiation
      patterns.

PMID- 19759688
TI  - Circular Fourier analysis of arbitrarily shaped optical fibers.
AB  - Propagation constants of weakly guiding optical fibers with arbitrary shapes can
      be efficiently calculated through a limited circular Fourier expansion of the
      wave equation, with a direct numerical integration.

PMID- 19759690
TI  - Conjugate generation and beam steering by nearly degenerate four-wave mixing in
      waveguide arrays.
AB  - We analyze the frequency-shifted conjugate beam generated by nearly degenerate
      four-wave mixing in an array of single-mode waveguides. We show that if the array
      sufficiently samples the signal beam, a high-quality conjugate will be generated
      when the pump beams are counterpropagating. The ability of a waveguide mode to
      couple to incoming beams over a range of incident directions relaxes the strict
      phase-matching requirement present in bulkmedia four-wave mixing. A shift in the
      propagation direction of one of the pump beams changes the propagation direction
      of the generated beam while maintaining the spatial phase coherence.

PMID- 19759691
TI  - Probability distribution of phase-induced intensity noise generated by
      distributed-feedback lasers.
AB  - Highly non-Gaussian, short-tailed photocurrent distributions due to laser-phase
      induced intensity noise have been observed in fiber-optic systems employing
      distributed-feedback lasers and wideband receivers. This behavior, which has
      implications for the correct prediction of performance in systems containing
      intentional or spurious interferometers, results from the cosinusoidal
      nonlinearity introduced by the interference process. The laser frequency noise is
      thereby converted to non-Gaussian intensity fluctuations at the system output.
      The intensitynoise statistics rapidly revert to Gaussian form, however, in
      systems whose receiver bandwidth is smaller than the laser linewidth.

PMID- 19759692
TI  - n-Soliton solution of the modified nonlinear Schrodinger equation.
AB  - An n-soliton solution of the modified nonlinear Schrodinger equation is
      presented, and its relationship to the nonlinear Schrodinger equation is given.

PMID- 19759693
TI  - Lensless imaging through phase-conjugated backscattering in SF(6).
AB  - A phase-conjugate mirror based on stimulated Brillouin scattering in gaseous
      SF(6) at 248 nm was used for pattern transfer. We measured the pressure
      dependence of backscattering efficiency of the Brillouin mirror, which approached
      40% reflectivity and was limited by the onset of gas breakdown. Measurement of
      the image contrast ratio showed high statistical fluctuation due to the threshold
      behavior of Brillouin scattering.

PMID- 19759694
TI  - Order-of-magnitude reduction of the photorefractive response time in rhodium
      doped Sr(0.6)Ba(0.4)Nb(2)O(6) with a dc electric field.
AB  - We present what is to our knowledge the first report on the photorefractive
      properties of Rh-doped Sr(0.6)Ba(0.4)Nb(2)O(6) and experimental results showing a
      reduction of the photorefractive two-beam coupling response time by more than an
      order of magnitude with an external dc field of 10 kV/cm.

PMID- 19759695
TI  - Self-pumped phase conjugation with nanosecond pulses in strontium barium niobate.
AB  - We report the observation of self-pumped phase conjugation by means of internal
      reflection in a photorefractive medium produced by a series of intense nanosecond
      pulses. Nanosecond pulses from a YAG laser ranging in intensity from 9 x 10(4) to
      9 x 10(5) W/cm(2) were used. The crystal was rhodium-doped strontium barium
      niobate. The conjugate signal began with the first pulse, and the time to reach
      63% of its equilibrium value scaled as I(-2). The equilibrium reflectivity was
      29%. A similar cw experiment with the 514-nm line of an argon laser produced a
      response time that scaled as I(-1.1).

PMID- 19759696
TI  - Effects of bending on multimode step-index fibers.
AB  - The influence of bends on light propagation in a step-index, nearly single-mode
      fiber is examined. We extend our theoretical results to the case of our
      particular fiber, and our experiments show good agreement with theory.

PMID- 19759697
TI  - Solitons emerging from pulses launched in the vicinity of the zero-dispersion
      point in a single-mode optical fiber.
AB  - It is shown that solitons emerging from pulses launched with frequencies at, or
      close to, the zero-dispersion point in a single-mode optical fiber are ordinary
      bright solitons corresponding to the nonlinear Schrodinger equation. These
      solitons are inherently frequency shifted into the anomalous-dispersion regime,
      where the third-order dispersion acts as a small perturbation. We therefore
      conclude that an optical-soliton-based communication system should be designed
      with the carrier frequency in the anomalous-dispersion regime but not too close
      to the zero-dispersion point, where the formation of an unwanted dispersive-wave
      component would degrade the system performance.

PMID- 19759698
TI  - Soliton intensity-dependent polarization rotation.
AB  - We show experimentally and numerically that intensity-dependent polarization
      rotation does not lead to pulseshape distortions for fundamental solitons because
      the soliton rotates as a unit. We demonstrate an optical limiter based on
      nonlinear polarization rotation in a standard, single-mode fiber followed by a
      polarizer. The output pulse shape from the limiter resembles that of the input,
      although the pulse width may be different.

PMID- 19759699
TI  - Nonstationary simulation of nonlinearly coupled TE-TM waves propagating down
      dielectric slab structures by the step-by-step finite-element method.
AB  - Propagation phenomena of two nonlinearly coupled orthogonal waves in a slab
      waveguide are demonstrated numerically. It is shown that the propagation behavior
      is strongly dependent on the particular nonlinear mechanism as well as on the
      optical power allotted to each polarization component.

PMID- 19759700
TI  - Two-dimensional coupled-mode theory for modeling leaky-mode arrays.
AB  - The use of a two-dimensional coupled-mode theory for modeling buried-ridge
      waveguide index-guided arrays in general and leaky-mode arrays in particular is
      described. This formalism provides a framework for understanding the complicated
      modal structure of leaky-mode arrays by expressing their modes as linear
      combinations of the two dimensional modes of the buried-ridge waveguides and the
      active-region confinement structure. As a result, the inherently large parameter
      space of these devices may be collapsed dramatically so that the device behavior
      is describable in terms of only the propagation constant mismatch between the
      buried-ridge modes and the activeregion modes and their coupling coefficient.

PMID- 19759701
TI  - Photorefractive integrated-optical switch arrays in LiNbO(3).
AB  - A new optical switch design is reported that consists of two sets of parallel
      channel waveguides intersecting at right angles. Arrays based on Ti:LiNbO(3)
      technology, with waveguide intersections iron doped to provide photorefractive
      sensitivity, have been fabricated. Interfering guided beams are used to write
      index gratings at the waveguide intersections, which in turn diffract a portion
      of an incident signal beam into the crossing waveguide. Arrays ranging from 15 x
      15 up to 50 x 50 waveguides are constructed in an active area of 5 mm x 5 mm.
      Diffraction efficiency and writing-time measurements are reported along with a
      proposal for a practical architecture.

PMID- 19759702
TI  - High-power superfluorescent fiber source.
AB  - The output of a broad-stripe laser diode is used to pump a neodymium-doped offset
      core fiber to produce over 80 mW of superfluorescent emission. The power
      dependence of the spectral bandwidth shows a minimum near 10 mW that increases to
      5 nm at 80 mW. Above 15 mW, obtaining a smooth spectrum depended on the specific
      configuration.

PMID- 19759703
TI  - Solar-pumped Er,Tm,Ho:YAG laser.
AB  - Direct solar illumination was used to pump a 5-mm-diameter 62-mm exposed-length
      rod of Er,Tm,Ho:YAG to achieve a quasi-cw lasing of the Ho ion at an average
      power of 12 W. The solar radiation was chopped at a 20% duty cycle to avoid
      overloading of the cooling system. The peak power output was more than 65 W
      during the chopper's open times. The slope efficiency is 3.8%, and the threshold
      input energy is approximately 100 W. The laser was operated for long times (up to
      hours) while maintaining its performance. This is, to our knowledge, the first
      directly solar-pumped laser operating at 77 K.

PMID- 19759704
TI  - High-intensity subpicosecond XeCl laser system.
AB  - A terawatt-class laser, based on the amplification of subpicosecond pulses in
      XeCl discharge amplifiers, is described. The system generates 250-mJ, 335-fsec
      pulses at a sustained 1-Hz repetition rate. Using f/3.7 optics, focal-spot
      dimensions of 3.4 microm x 4.1 microm are measured for the fully amplified output
      beam, thus demonstrating a mean focalvolume intensity of 4.6 x 10(18) W/cm(2).
      With f/l optics, this system is therefore capable of producing a focused
      intensity of 6.4 x 10(19) W/cm(2).

PMID- 19759705
TI  - Efficient room-temperature operation of a flash-lamp-pumped, Cr,Tm:YAG laser at
      2.01 microm.
AB  - We report what is to our knowledge the first room-temperature operation of an
      efficient flash-lamp-pumped Cr,Tm:YAG laser at 2.014 microm. Thresholds as low as
      43 J, output energies exceeding 2 J, and slope efficiencies as high as 4.5% have
      been achieved using a compact diffuse-reflecting pump cavity. These efficiencies
      are an order of magnitude higher than those previously reported for a 2.01-microm
      Cr,Tm:YAG laser operated at cryogenic temperatures.

PMID- 19759706
TI  - High-frequency acousto-optic mode locker for picosecond pulse generation.
AB  - We modeled, designed, and built a 500-MHz acousto-optic mode locker with a
      diffraction efficiency of 28% per 1 W drive power. The transducer is zinc oxide
      sputtered onto a sapphire substrate. A new figure of merit is defined for the
      mode-locker design, which indicates that sapphire is a good substrate material.
      Pulse widths of less than 10 psec with an average power of 150 mW were achieved
      from a 500-MHz pulse-rate, diode-pumped, cw mode-locked Nd:YLF laser using a pump
      power of 700 mW.

PMID- 19759707
TI  - Measurements of the phase shift and reshaping of terahertz pulses due to total
      internal reflection.
AB  - Using time-domain spectroscopic techniques with freely propagating
      electromagnetic beams of terahertz pulses, we have measured the phase shift and
      reshaping of subpicosecond pulses due to total internal reflection from a
      crystalline quartz prism. Our measured value of the phase shift is in excellent
      agreement with the theoretical prediction.

PMID- 19759708
TI  - Generation of terahertz-rate trains of femtosecond pulses by phase-only
      filtering.
AB  - We describe a simple linear filtering technique for transforming individual
      femtosecond light pulses into terahertzrepetition-rate bursts of femtosecond
      pulses. By using phase-only filtering, high efficiency is achieved. Pulse
      repetition rates approaching 6 THz are obtained.

PMID- 19759709
TI  - Measurements of the anisotropic nonlinear refractive-index coefficients of ruby.
AB  - The real part n(2)' of the complex nonlinear refractive-index coefficients of
      ruby crystal (Cr(3+):Al(2)O(3)) are measured by the Mach-Zehnder interferometric
      method. The n(2)' values measured at 514.5 nm for the light polarization
      perpendicular (sigma) and parallel (pi) to the crystal c axis are (2.81 +/- 0.36)
      10(-8) and (1.33 +/- 0.17) x 10(-8) cm(2)/W, respectively. From the results
      obtained the ratio of the polarizability difference between the excited and
      ground states of Cr(3+) in ruby for sigma polarization to that for pi
      polarization is found to be 1.05 +/- 0.30.

PMID- 19759710
TI  - Frequency locking of a laser by injected atomic coherence.
AB  - We consider a single-mode unidirectional ring laser containing a homogeneously
      broadened two-level medium whose atoms are injected in a coherent superposition
      of states. Provided that appropriate phase-matching conditions are met, the
      injected coherence contributes directly to the polarization of the medium and
      hence to the laser gain. We assume that the field is classical and perfectly
      phase matched with the injected coherence. We find that laser oscillation can
      occur below the usual laser threshold, and even in the absence of an inversion,
      with a frequency locked to the atomic line center. Mode locking is unstable for
      sufficiently strong relative excitation.

PMID- 19759711
TI  - How fast is excitonic electroabsorption?
AB  - Many semiconductor light modulators rely on changes in excitonic absorption
      induced by electric fields. We study their temporal response in the framework of
      a one-dimensional model, for which we solve exactly the timedependent Schrodinger
      equation. For a homogeneously broadened system, the electroabsorption response
      time is found to be simply the inverse of the (field-induced) exciton linewidth,
      which can be as short as 50 fsec.

PMID- 19759712
TI  - Saturation spectroscopy in optically thick three-level gas media.
AB  - High-contrast transmission spectra arising from saturated absorption in optically
      thick Doppler-broadened threelevel media are analyzed within the formalism of
      Maxwell-Bloch-type equations. It is found that although in the strong pumping
      engine propagation-induced line narrowing and light-shift elimination occur,
      spectral features lying within the natural linewidth cannot be resolved.

PMID- 19759713
TI  - High-sensitivity surface-photoacoustic spectroscopy.
AB  - The sensitivity of surface-acoustic-wave detection is extended by several orders
      of magnitude to a surface-specific absorbance of alphal ~ 10(-9) for a power
      density of 1 GW/cm(2) using a narrow-bandwidth interdigitated surface
      acousticwave detector and an optical irradiation pattern to provide a matched
      acoustic signal. Major advantages include narrow-bandwidth detection and a large
      irradiated area that permits more optical energy on the sample. A rapid,
      nondestructive, reproducible liquid-bonding technique, which permits the
      extension of these measurements to a wide variety of samples, is demonstrated.
      Results for AlN and ZrO(2) films (alphal ~ 10(-4)) and fused-silica substrates
      (alphal ~ 10(-6)-10(-7)) are reported.

PMID- 19759714
TI  - Nonlinear holography: a novel approach for creating near-infrared narrow-notch
      reflectors.
AB  - It is shown that the nonlinearity in the response function of a holographic
      medium can lead to formation of gratings at the sum and difference frequencies of
      the exposing standing-wave patterns. This nonlinear feature can be utilized to
      create reflection holograms at spectral regions where conventional techniques are
      not applicable. Specifically, it is suggested that near-infrared or infrared
      rejection filters that are sensor centered can be obtained by using this
      approach.

PMID- 19759715
TI  - Measurement of OH rotational temperatures in a flame using degenerate four-wave
      mixing.
AB  - Temperatures have been measured in a laminar premixed propane-air diffusion flame
      using degenerate four-wave mixing (DFWM) of the OH radical. The spectra were
      recorded simultaneously with laser-induced fluorescence through the (0, 0) band
      of the OH A(2)Sigma-X(2)II transition. Individual rotational lines are more
      clearly resolved in the DFWM spectrum than in the laser-induced fluorescence
      spectrum, although both are power broadened at laser intensities of 1-2 MW/cm(2)
      at 307 nm. Rotational temperatures have been determined from the DFWM spectra and
      are in close agreement with temperatures measured with coherent anti-Stokes Raman
      spectroscopy of nitrogen.

PMID- 19759716
TI  - Multilayer system for a high-precision surface plasmon resonance sensor.
AB  - A multilayer surface plasmon resonance system was designed for high-precision
      chemical sensor applications. In this sensor, the angular distribution of
      reflectance from a thin metal film-which is in contact with a sample-is measured.
      An absorption peak is observed whose angular distribution of reflectance, owing
      to the excitation of surface plasmon resonance, is measured. The refractive index
      of the sample is determined from this peak angle. The resolution limit for
      refractive-index measurements is determined by the absorption peak width. We
      describe a multilayer system in which an additional layer is added to the
      conventional Kretschmann geometry; as a result, peak widths are significantly
      reduced. The angular distribution of reflectance is calculated using Fresnel's
      formulas and multiple-reflectance theory in order to understand the effect of
      thickness and refractive index of the additional layer. By optimizing the
      thickness of the layer, peak widths are reduced to approximately one third of
      that obtained using the Kretschmann geometry. Experimental results demonstrate
      the feasibility of this approach.

PMID- 19759717
TI  - Time-resolved two-photon-excited fluorescence detection of atomic hydrogen in
      flames.
AB  - We describe time-resolved fluorescence decay measurements of atomic hydrogen in
      20-Torr flames using twophoton, 205-nm excitation with 50-psec laser pulses.
      These studies provide measurements of the variations in collisional quenching
      rates of hydrogen atoms measured directly in combustion environments.

PMID- 19759718
TI  - Single-pass imaging through a thick dynamic distorter using four-wave mixing.
AB  - We have reconstructed images after a single pass through a thick, turbulent
      aberrator. The reconstructed image's resolution was independent of the presence,
      severity, and length of a hot-air aberrator (at least 50 times the collecting
      optics' depth of field). The slowly responding four-wave mixing medium,
      fluorescein-doped boric acid glass, averaged out rapidly varying intensity
      apodizations, which would otherwise degrade the reconstructed image quality.

PMID- 19759719
TI  - Blazed reflection micro-Fresnel lenses fabricated by electron-beam writing and
      dry development.
AB  - The microfabrication of a blazed reflection micro-Fresnel lens (RMFL) using
      electron-beam writing and dry development is proposed and demonstrated. The
      electron-beam-written resist film made of polymethyl isopropenyl ketone and an
      aromatic azido compound achieved the blazed structure by O(2) plasma development.
      The surface roughness of the RMFL was improved without the bridge and scum. The
      fabricated RMFL exhibited the diffraction-limited characteristics. A high
      efficiency of 71% was obtained at a period of 10 microm. The margin for the
      electron-beam writing condition to achieve high efficiency was much broader than
      in the conventional process. This process would be effective for the fabrication
      of blazed RMFL's and other grating components.

PMID- 19759720
TI  - Electrically tunable liquid-crystal wave plate in the infrared.
AB  - Phase retardance of a liquid-crystal-based, electrically tunable wave plate as a
      function of voltage and incident light intensity at 10.6 microm is measured using
      the Stokes-MacCullaugh ellipsometry technique. At intensities of up to 900
      W/cm(2), device performance is found to be driven by thermal effects and not
      optically induced reorientation effects.

PMID- 19759721
TI  - Optical multichannel-scale range-tunable Fourier-transforming system: experiment.

PMID- 19759722
TI  - Evidence of saturation-enhanced switching at a nonlinear interface.

PMID- 19759723
TI  - Control of self-pumped phase-conjugate reflectivity using incoherent erasure.

PMID- 19759724
TI  - Photoinduced refractive-index changes in germanosilicate fibers.

PMID- 19759725
TI  - Method for analysis of complex refractive-index-profile fibers.

PMID- 19759726
TI  - Controllable integrated-optic polarization splitter - combiner.

PMID- 19759727
TI  - Quasi-cw-pumped Nd:YAG laser using a negative-branch unstable resonator with a
      phase-unifying output coupler.

PMID- 19759728
TI  - Partial-integration method for analysis of mode-locked semiconductor lasers.

PMID- 19759729
TI  - All-solid-state passively Q-switched mode-locked Nd-doped fiber laser.

PMID- 19759730
TI  - Ultrashort-pulse energy-extraction measurements in XeCl amplifiers.

PMID- 19759731
TI  - Improvement of slab-laser beam divergence by using an off-axis unstable - stable
      resonator.

PMID- 19759732
TI  - High-peak-power operation of a diode pumped Q-switched Nd:YAG laser.

PMID- 19759733
TI  - Third-order group-velocity dispersion in a colliding-pulse mode-locked dye laser.

PMID- 19759734
TI  - Supercontinuum generation at 248 nm using high-pressure gases.

PMID- 19759736
TI  - Continuous-wave mode-locked and dispersion-compensated femtosecond optical
      parametric oscillator.

PMID- 19759735
TI  - Tunable, femtosecond soliton generation from amplified continuous-wave diode
      laser signals.

PMID- 19759737
TI  - Enhanced squeezing in a squeezed vacuum.

PMID- 19759739
TI  - Polarization-independent, broadband, bistable, 2 x 2 optical exchange switch.

PMID- 19759738
TI  - Relaxation-oscillator detection of optogalvanic spectra.

PMID- 19759740
TI  - Electro-optic effects in thin-film lanthanum-doped lead zirconate titanate.
AB  - We report the deposition and characterization of highly oriented thin-film
      lanthanum-doped lead zirconate titanate (28/0/100) on fused-silica substrates by
      rf planar magnetron sputtering. The quadratic electro-optic effect gives a
      birefringence of Deltan ~ 0.018 at an applied field of 39 kV/mm. Optical
      modulation at a switching speed of 3 nsec (instrumentation limited) is achieved.
      Results of optically induced decay of the birefringence in these films are also
      reported.

PMID- 19759741
TI  - Berry's phase in optical interferometry: a simple derivation.
AB  - When an electromagnetic wave propagates around a circuit that is closed in k
      space, the value of Berry's topological phase can be deduced by solving Maxwell's
      equations in a rotating frame of reference.

PMID- 19759742
TI  - Observation of input and output structural resonances in the Raman spectrum of a
      single spheroidal dielectric microparticle.
AB  - The Raman spectrum measured on a slowly evaporating liquid droplet trapped by
      radiation pressure shows two sets of resonances: one set of strong but narrow
      resonances that can be interpreted as resonances in the transmitted field (input
      resonances) and a second set caused by resonances in the inelastically scattered
      field (output resonances). The second set is much weaker, but its peaks are
      spectrally broader by an order of magnitude. Comparison with calculated input
      resonances and comparison of the elastically scattered light with the calculated
      spectrum indicate that the optically levitated particle is spheroidal in shape.

PMID- 19759743
TI  - Effect of multiple scattering on the intensity fluctuation of speckle
      backscattered from a randomly rough metal surface.
AB  - In laser speckle backscattered to the far field from a randomly rough metal
      surface the effect of multiple scattering on the intensity fluctuation g((2))(0)
      is investigated. The s-polarized (perpendicular to the incidence plane) laser
      beam is incident with an angle of -30 degrees on the slowly rotating ground
      glass. The ground surface is aluminum coated, and the angular distributions of
      the mean intensity and the g((2))(0) of the dynamic speckle are measured. The
      results show that depolarization is significant in the mean intensity, and
      g((2))(0) is found to be less than 2 in the Gaussian scattering region. The
      relation between the depolarization and g((2))(0) is derived theoretically and
      verified experimentally.

PMID- 19759744
TI  - Application of optical cross talk to switching between bistable soliton states.
AB  - The dynamics of bistable soliton propagation and switching in a fiber whose
      intensity-dependent refractive index is described by the linear plus smooth-step
      model is numerically investigated under conditions where the fiber is
      evanescently coupled to an identical, initially empty, parallel fiber. The
      initially empty fiber can perform a number of useful operations on solitons in
      the first fiber, which could be of interest in optical device design.

PMID- 19759745
TI  - Intracavity sum-frequency generation of blue light in a synchronously mode-locked
      cw dye laser.
AB  - Intracavity upconversion is demonstrated in a synchronously pumped Styryl 9M dye
      laser. Picosecond blue pulses at 463 nm are generated by type II nearly
      noncritical phase-matched intracavity sum-frequency mixing in KTiOPO(4) of the
      dye-laser pulses at 824 nm and injected pulses from a mode-locked cw Nd:YAG laser
      at 1064 nm.

PMID- 19759746
TI  - Power-flux-dependent polarization of nonlinear surface waves.
AB  - The complete set of Maxwell's equations coupled by means of intrinsic
      nonlinearities in Kerr-type media has been analyzed and the integrated power flux
      has been found as a function of refractive index for hybrid TE-TM nonlinear
      surface waves. We demonstrate that for a fixed refractive index the electric
      field vector of the nonlinear surface waves rotates with an adiabatic increase of
      the power flux from pure TE polarization at the threshold to pure TM polarization
      at the cutoff, passing through all possible hybrid polarization states for
      intermediate power fluxes.

PMID- 19759747
TI  - Unification of nonlinear-optical fiber devices.
AB  - Nonlinear coupling can be described in a universal form applicable to a general
      class of optical fiber devices involving the interaction of two modes. By knowing
      the solution to one type of device, we then have the solution to all other types.
      For example, the descriptions of birefringent fibers used as switches and
      amplifiers have their direct counterparts in directional (twin-core) couplers,
      found by merely redefining the meaning of subscripts in equations or on the phase
      space portrait. The key to this unification follows, not by actually solving any
      one problem but rather by interrelating the coupling of normal modes with the
      coupling of submodes, e.g., the individual core modes of directional couplers.

PMID- 19759748
TI  - Forward wide-angle light propagation in semiconductor rib waveguides.
AB  - We derive and examine a new nonparaxial wide-angle equation for unidirectional
      light propagation. We then develop a rapid unitary solution procedure utilizing
      both the split-step fast-Fourier-transform and finite-difference techniques. Our
      calculated losses for the test case of a strongly guiding semiconductor rib
      waveguide Y junction are in good agreement with the results of Fresnel equation
      methods.

PMID- 19759749
TI  - Semiconductor-laser-pumped, cw mode-locked Nd:phosphate glass laser oscillator
      and regenerative amplifier.
AB  - An all-diode-pumped Nd:glass mode-locked laser oscillator and regenerative
      amplifier are described. The oscillator produces a train of 58-psec transform
      limited pulses at a 113.6-MHz repetition rate. The output of the oscillator is
      amplified by a regenerative amplifier. The pulse energy at the input of the
      amplifier is 39 pJ. The amplifier provides a gain of 51 dB, producing 5.4-microJ
      pulses at a repetition rate of 355 Hz. The amplifier produces no measurable
      broadening of the pulse.

PMID- 19759750
TI  - Compression of picosecond pulses from diode lasers using a modified grating-pair
      compressor.
AB  - Optical pulses from gain-switched diode lasers were compressed using a grating
      pair compressor containing an internal telescope. Original pulses of 20-30 psec
      were compressed to 5-7 psec, with the largest compression factor ~5. Diode-laser
      pulse compression is well modeled by transmission of Gaussian pulses with excess
      bandwidth through a dispersive system.

PMID- 19759751
TI  - Self-starting condition for additive-pulse mode-locked lasers.
AB  - We analyze self-starting in additive-pulse mode-locked lasers and find that
      dynamic gain saturation can play a determining role. A simple condition for self
      starting is presented for comparison with experiments on different laser systems.

PMID- 19759752
TI  - Switching types and all-optical flip-flop operations in a ring cavity with four
      nonlinear elements.
AB  - We consider an optical ring cavity with four nonlinear elements and investigate
      its all-optical flip-flop operation and the types of switching between its
      multiple stable states. All-optical flip-flop operation is shown to exist, and
      the possible switching modes are determined. We also discuss the difference
      between the slowly varying input and pulse-injection processes. Moreover a
      procedure to obtain the preinjection states that are needed for operation is
      proposed.

PMID- 19759753
TI  - Nonlinear-optical absorption in InGaAs/InAlAs multiple quantum wells.
AB  - We have measured the room-temperature intensity dependence of the optical
      transmission of an In(0.53)Ga(0.47)As/In(0.52)Al(0.48)As multiple-quantum-well
      structure from 1.5 to 1.7 microm. The absorption is calculated from the
      transmission by taking into account the wavelength dependence of the reflection
      coefficients. An intensityof 15 kW cm(-2) is required to reduce the absorption by
      one half for excitation at the edge of the 1H-lC transition absorption band. For
      intensities exceeding 10(7) W cm(-2), complete saturation of the absorption is
      observed. A theoretical model is described that fits the intensity dependence of
      the absorption right upto saturation at two wavelengths and predicts a carrier
      lifetime of 0.75 nsec, which has been confirmed by independent measurements.

PMID- 19759754
TI  - White-light joint-transform correlator.
AB  - The spatial and temporal coherence requirements in the formation of the joint
      transform hologram and in the readout process are described, and experimental
      results are given.

PMID- 19759755
TI  - 248-Bit optical data storage in Eu(3+):YAlO(3) by accumulated photon echoes.
AB  - The successful storage and retrieval of 248-bit temporal optical data in
      Eu(3+):YAlO(3) by accumulated photon echoes is reported. Owing to the long
      storage time of this crystal, the input data can be written bit by bit by quickly
      varying the separation of two laser pulses, while the stored data are recalled
      simultaneously after some storage period, which extends up to a few hours. The
      maximum data length, previously thought to be limited by the optical dephasing
      time T(2), has been found to be four times shorter than T(2) and attributable to
      spectral diffusion.

PMID- 19759756
TI  - Two-mode fiber-optic resonant ring interferometer as a sensor.
AB  - A fiber-optic resonant ring interferometer using a directional coupler was
      fabricated using a single-mode fiber. It is an unbalanced interferometer
      functioning on the optical path-length difference. We have measured the phase
      shift caused by temperature changes with this setup and can determine the
      direction of temperature variance when a light source of appropriate wavelength
      is used. Using a prism output coupler for an optical fiber in the resonant ring
      interferometer, we determine the intensity variation of the radiation pattern
      caused by the thermally induced phase shift.

PMID- 19759757
TI  - Laser-diode microscope that generates weakly speckled images.
AB  - We describe a laser-diode microscope that produces images that are almost free of
      speckles. Speckle reduction is achieved by large-signal current modulation of the
      laser diode and the introduction of a dispersing section as part of the
      illumination arrangement.

PMID- 19759758
TI  - Delay of explosive vaporization in pulsed laser-heated droplets.
AB  - Measurements of time delays for explosion of pulsed CO(2) laser-heated droplets
      are presented. A simple model based on classical nucleation theory in superheated
      liquids, which neglects heat and mass transport, is used to interpret the data.
      The model shows good agreement with the experimental observations.

PMID- 19759759
TI  - Orientational dependence of photorefractive two-beam coupling in InP:Fe.
AB  - We present the theory for photorefractive two-beam coupling without optical
      activity in cubic crystals rotated around the [110] axis. We also describe two
      beam coupling experiments in InP:Fe that fit the theory closely. The 15.5% gain
      enhancement for grating wave vectors aligned along the <111> directions is
      demonstrated explicitly.

PMID- 19759760
TI  - Shallow buried waveguides made by purely thermal migration of K+ ions in glass.
AB  - Buried planar optical waveguides made by a purely thermal backdiffusion K(+)
      Na(+) ion-exchange process have been demonstrated, for the first time to our
      knowledge, on soda-lime glass substrates. The potassium-ion concentration profile
      is determined using a scanning electron microscope technique, which is then
      correlated to the numerical simulation of the ion-exchange fabrication process.

PMID- 19759761
TI  - Preferential operation of an end-pumped Nd:YAG laser in high-order Laguerre-Gauss
      modes.
AB  - A small Nd:YAG laser with plano-concave resonator end pumped by a dye laser is
      observed to possess single Laguerre-Gauss transverse modes as the lowest-loss
      modes. This anomalous behavior occurs when the transverse dimension of the gain
      spot is much smaller than the fundamental TEM(00)-mode spot size of the
      resonator; the Laguerre-Gauss transverse-mode order varies with resonator length.

PMID- 19759762
TI  - Observation of mode locking in a synchronously pumped Nd:YAG laser.
AB  - We report on the mode-locking behavior of a 1.06-microm Nd:YAG ring oscillator
      synchronously pumped by a 76-MHz, 20-psec dye laser at 0.59 microm with an
      average power of 600 mW. Gain modulation is based on relaxation from the pump
      band to the upper laser level with a time constant (minimum gain modulation time)
      of 470 psec; stable modelocked operation is achieved with a gain modulation of
      only 10(-4). Preliminary results give a minimum pulse width of 140 psec and
      suggest a novel way of mode locking rare-earth waveguide lasers.

PMID- 19759763
TI  - Active frequency stabilization of a 1.062-microm, Nd:GGG, diode-laser-pumped
      nonplanar ring oscillator to less than 3 Hz of relative linewidth.
AB  - We present results on the frequency stabilization of two diode-laser-pumped ring
      lasers that are independently locked to the same high-finesse interferometer. We
      measure the relative frequency stability by locking the lasers one free spectral
      range apart and observing the heterodyne beat note. The resultant beat note width
      of 2.9 Hz is consistent with the theoretical system noise-limited linewidth and
      is approximately 20 times that expected for shot-noise-limited performance.

PMID- 19759764
TI  - Effect of intrapulse stimulated Raman scattering on soliton-effect pulse
      compression in optical fibers.
AB  - The effect of intrapulse stimulated Raman scattering (ISRS) on the quality of
      soliton-effect pulse compression is analyzed by solving the generalized nonlinear
      Schrodinger equation numerically. The results show that ISRS can improve the
      performance of soliton-effect pulse compressors both qualitatively and
      quantitatively. The compressed pulse is shorter with a higher peak power when
      ISRS is taken into account. Furthermore it is pedestal free as it separates from
      the background. The separation is due to the soliton self-frequency shift
      initiated by the process of ISRS. It can also be understood in terms of the
      soliton decay. The optimum fiber length is found to be longer than that expected
      in the absence of ISRS.

PMID- 19759765
TI  - Optical implementation of large-scale neural networks using a time-division
      multiplexing technique.
AB  - A new architecture for optical implementation of large-scale neural networks is
      proposed. This architecture is based on a time-division-multiplexing technique,
      in which both the neuron state vector and the interconnection matrix are divided
      in the time domain. Computer simulation and experimental results for associative
      memories show the effectiveness in implementing large-scale networks.

PMID- 19759766
TI  - Analysis of neodymium-to-erbium energy transfer in yttrium aluminum garnet with a
      nonuniform-distribution model.
AB  - Data indicating energy transfer between erbium and neodymium in yttrium aluminum
      garnet have been analyzed. The observed rate of transfer cannot be explained by
      the standard model, which assumes that the transfer occurs through the dipole
      dipole interaction between randomly distributed acceptors and donors. A new model
      for energy transfer is presented in which donors and acceptors affect each
      other's placement in the crystal. A much closer fit to the observed experimental
      data is obtained with this model and by assuming that the location of erbium ions
      in the nearest-neighbor sites to neodymium ions is not energetically favorable.

PMID- 19759767
TI  - Generation of macroscopic superpositions in a micromaser.
AB  - At low temperatures steady-state macroscopic superpositions can be generated in
      the field of a micromaser pumped by a stream of two-level atoms injected in a
      coherent superposition of their upper and lower states. The onset of these
      superpositions resembles a second-order phase transition, with the control
      parameter being the ratio of the atomic injection rate to the cavity damping
      rate.

PMID- 19759768
TI  - 422.7-nm atomic filter with superior solar background rejection.
AB  - A novel atomic resonance filter with powerful solar background rejection is
      proposed. The filter wavelength matches the g Fraunhofer line at 422.7 nm. Atomic
      filtering occurs within the singlet manifold of neutral calcium. Superior
      sunlight discrimination arises mainly from two factors: overlay with an intense
      Fraunhofer line and signal levels devoid of fine and hyperfine structures. The
      new filter should exhibit high throughput and low noise.

PMID- 19759769
TI  - Soliton-collision interferometer for the quantum nondemolition measurement of
      photon number: numerical results.
AB  - Using analytic theory and numerical experiments, we show that a quantum
      nondemolition measurement of the photon number of optical solitons in a single
      mode optical fiber can be made. We describe the soliton-collision interferometer
      with which we propose to make this measurement and discuss simulations of the
      performance of this interferometer.

PMID- 19759770
TI  - Fabrication of birefringent gratings using nonlinear polysilane thin films.
AB  - Birefringence is shown to be induced in polysilane thin films by the process of
      chain scission induced by nonlinear absorption at visible wavelengths. This
      writable birefringence is easy to control and can be used for the fabrication of
      birefringent gratings and other optical devices.

PMID- 19759771
TI  - Polarization-based optical logic using laser-excited gratings.
AB  - We present a novel way of performing optical logic. The proposed logic device is
      based on the polarization switching observed in the first-order diffraction from
      a laser-excited grating in a dye-doped solid.

PMID- 19759772
TI  - Two-wavelength operation of the nonlinear fiber loop mirror.
AB  - We describe the two-wavelength operation of the nonlinear fiber loop mirror. In
      this mode of operation a high-power signal at one wavelength switches a low-power
      signal at another wavelength. This device is investigated both theoretically and
      experimentally. The experimental results show that the nonlinear loop mirror
      performs as an optical modulator that consists of all-fiber components.

PMID- 19759773
TI  - Residual aluminum and its dichroism in anodized alumina thin films.
AB  - Aluminum is anodized in a sulfuric acid solution with a large current density. It
      is shown for the first time to our knowledge that the aluminum is only partially
      oxidized in the process and that the alumina thin film containing the residual
      aluminum acts as a polarizer with a large extinction ratio in the infrared
      wavelength region.

PMID- 19759774
TI  - Light scattering from cylindrical structures on surfaces.
AB  - Light scattering from a dielectric cylindrical structure on a surface by a plane
      wave with field vector along the cylinder axis is calculated with a modification
      of the coupled-dipole method. The interaction matrix is calculated with the use
      of both the direct contribution of a polarization current filament and its
      reflection from the surface. The reflected cylindrical waves are computed with
      the use of the Sommerfeld-type integral expression. Light scattering from
      structures of arbitrary cross section and the size of the order of a wavelength
      can be quickly determined with this method.

PMID- 19759775
TI  - Formation of transverse spatial ring structures in increasing-absorption optical
      bistability.
AB  - We report the observation of transverse spatial ring structures in the
      transmitted beam profile using a thin CdS platelet that exhibits increasing
      absorption optical bistability. The observed ring structure is in good agreement
      with our theoretical predictions.

PMID- 19759776
TI  - Instability in an illuminated nonlinear waveguide: a phase-conjugation effect.
AB  - We consider a laser beam incident normally upon a waveguide with a Kerr
      nonlinearity. Although the laser is uniform in the plane of the waveguide, we
      show that the waveguide fields can be unstable to growth, forming coherent
      periodic structures. The initial, exponential time dependence is determined, and
      we find a steady-state solution. Finally, we note that the mechanism necessary
      for this instability is that responsible for phase conjugation by means of
      degenerate four-wave mixing.

PMID- 19759777
TI  - Resonant photodiffractive four-wave mixing in semi-insulating GaAs/AlGaAs quantum
      wells.
AB  - We have performed photodiffractive four-wave mixing in semi-insulating multiple
      GaAs/AlGaAs quantum wells at a wavelength of 0.83 microm. The quantum wells were
      made semi-insulating by proton implantation, which introduces defects that are
      available to trap and store charge during holographic recording. The experiments
      demonstrate how photodiffractive behavior using the large resonant nonlinearities
      of quantum-confined excitons yields highly sensitive material for optical image
      processing. When pump powers of 1 mW/cm(2) are used, the measured sensitivity is
      2 orders of magnitude greater than that of bulk, nonresonant photorefractive
      semiconductors.

PMID- 19759778
TI  - Second-harmonic generation in ferroelectric liquid crystals.
AB  - We present phase-matched, second-harmonic generation in the ferroelectric liquid
      crystal material SCE9 (manufactured by BDH Ltd.). From the analysis of these
      results, the absolute values of all nonzero components of the d tensor have been
      obtained. A direct comparison between this material and the most efficient
      ferroelectric liquidcrystal material reported so far (ZLI3654) is made, which
      shows that SCE9 is four times more efficient at frequency doubling. At the phase
      matching angle (theta = 19.1 degrees ) a d(eff) of 0.010(1) x 10(-12) m/V is
      measured. The results are consistent with near uniaxiality, the extent of which
      has been determined from experimental data (n(y) - n(x) = 0.0003, n(2) - n(x) =
      0.17).

PMID- 19759779
TI  - Optical waveguiding in a single-crystal layer of germanium silicon grown on
      silicon.
AB  - Low-loss waveguiding at lambda = 1.3 microm has been observed in a partially
      strained, 10-microm-thick, single-crystal layer of Ge(0.1)Si(0.9) grown by
      chemical-vapor deposition upon an intrinsic (100) silicon substrate. The TM-mode
      propagation loss in the multimode planar guide was 1.9 dB/cm.

PMID- 19759780
TI  - Electronically tunable, 1.55-microm erbium-doped fiber laser.
AB  - An erbium-doped, silica-based fiber laser was electronically tuned over two
      ranges from 1529.6 to 1533.3 nm and from 1543.8 to 1563.0 nm with more than 13 mW
      of maximum power. The tuning element was an intracavity acousto-optic modulator
      (Bragg cell) configured to feed back the first-order, frequency-shifted deflected
      beam. The maximum optical/acoustic tuning coefficient was -15 nm/MHz.

PMID- 19759781
TI  - Determination of the scattering and absorption lengths from the temporal profile
      of a backscattered pulse.
AB  - The temporal profiles of the backscattered pulse from random media are studied
      experimentally with femtosecond laser and streak-camera technologies. For a
      weakly scattering medium, the temporal profile of a backscattered pulse can be
      described by a simple exponential function. In the strongly scattering regime the
      temporal profile becomes nonexponential. The attenuation lengths arising from
      scattering and absorption can be directly determined from an analysis of the
      temporal profile of the backscattered pulse.

PMID- 19759782
TI  - Optoelectronic chip implementation of a quadratic associative memory.
AB  - High-order associative memories are of interest because of their potentially
      large storage capacity. We describe an optoelectronic implementation of a second
      order, or quadratic, associative memory. The two-layer network is based on an
      inner-product representation, which allows for a compact implementation using an
      optical chip design. Experimental results obtained from our system are discussed.

PMID- 19759783
TI  - Measurement of the subnanosecond, nonradiative relaxation time from excited
      states of Nd(3+) in a Nd:YAG crystal.
AB  - We have time resolved the nonradiative relaxation from the (4)G(7/2) manifold to
      the upper laser level (for lambda = 1.06 microm) of Nd(3+) in a Nd:YAG crystal.
      This has been performed by monitoring the onset of gain for the associated
      (4)F(3/2)-(4)I(11/2) transitionfollowing excitation of the (4)G(7/2) pump band by
      a 40-psec, 0.53-micro m pump pulse. The nonradiative relaxation time was found to
      be 470 +/- 60 psec at room temperature and no shorter than 400 psec at 440 K.

PMID- 19759784
TI  - Bistable spatial light modulator using a ferroelectric liquid crystal.
AB  - A bistable spatial light modulator is developed by utilizing optical bistability
      of ferroelectric liquid-crystal molecule.Both positive and negative images are
      read out by changing the polarity of applied electric pulses. A binary image is
      stored for more than 2 h, and gray-level operation is also possible during the
      gradual decay after writing.

PMID- 19759785
TI  - Efficient array illuminator using binary-optics phase plates at fractional-Talbot
      planes.
AB  - We describe a phase plate based on the fractional-Talbot effect that converts a
      single expanded laser beam into a regular array of uniformly illuminated
      apertures with virtually 100% efficiency. The size, spacing, and fill factor of
      the illuminated aperture grid can be freely chosen to interface with a variety of
      electro-optic devices. A binaryoptics phase plate is demonstrated that converts
      uniform illumination into an array of square illumination cells with a fill
      factor of 1/16.

PMID- 19759786
TI  - Ferroelectric-liquid-crystal/silicon-integrated-circuit spatial light modulator.
AB  - We present the design and characterization of a spatial light modulator (SLM)
      comprising a ferroelectric-liquid-crystal light-modulating layer on top of a
      silicon integrated circuit. Our SLM consists of two electrically addressed arrays
      on the same integrated-circuit die. The first, a 1 x 128 linear array with a 20
      microm center-to-center element spacing, used shift register addressing, while
      the second, a 64 x 64 square array with 60-microm pitch, used static random
      access memory addressing. The resulting SLM could be addressed at frame rates of
      up to 4.5 kHz and gave singleelement intensity contrast ratios of 12:1.

PMID- 19759788
TI  - Spherical chirolenses.

PMID- 19759787
TI  - Fast atomic line filter/field ionization detector.
AB  - An experimental demonstration of a fast atomic line filter/field ionization
      detector (FALF/FID) is presented. The FALF/FID detects incoming signal photons by
      resonant absorption in an atomic vapor cell containing a strong electric field.
      Excited atoms are electric-field ionized after further excitation to a Stark
      shifted Rydberg level by a pump laser tuned to a resonance in the ionization
      spectrum, providing an observed enhancement in the ionization rate of ten times
      over the continuum ionization threshold. Preliminary measurements of time
      response (<10 nsec) and quantum efficiency (>25%) indicate that with optimization
      the FALF/FID will provide high quantum efficiency, fast time response, and narrow
      linewidth detection.

PMID- 19759789
TI  - Eye-safe 2.1-Mu m Ho lidar for measuring atmospheric density profiles.

PMID- 19759790
TI  - Optical characteristics of supercontinuum generation.

PMID- 19759791
TI  - Aberration correction of acousto-optically modulated laser beams by phase
      conjugation.

PMID- 19759792
TI  - Observation of polarization instabilities and modulational gain in a low
      birefringence optical fiber.

PMID- 19759793
TI  - Electrostriction mechanism of soliton interaction in optical fibers.

PMID- 19759794
TI  - Operation of a 1-kHz pulse-pumped Ti:sapphire regenerative amplifier.

PMID- 19759795
TI  - Time-resolved coherent and incoherent components of forward light scattering in
      random media.

PMID- 19759796
TI  - Subpicosecond electromagnetic pulses from large-aperture photoconducting
      antennas.

PMID- 19759797
TI  - Programmable femtosecond pulse shaping by use of a multielement liquid-crystal
      phase modulator.

PMID- 19759798
TI  - Self-phase modulation of incoherent light.

PMID- 19759799
TI  - Magnetic circular differential scattering in FeF2.

PMID- 19759800
TI  - Coherent ringing in pulses from a mode-locked argon laser.

PMID- 19759801
TI  - Computer-generated holography in photorefractive materials.

PMID- 19759802
TI  - Compact and ultrafast holographic memory using a surface-emitting microlaser
      diode array.

PMID- 19759803
TI  - Diffraction efficiency of strong volume holograms.

PMID- 19759804
TI  - Optimality of the Holm procedure among general step-down multiple testing
      procedures.
AB  - We study the class of general step-down multiple testing procedures, which
      contains the usually considered procedures determined by a nondecreasing sequence
      of thresholds (we call them threshold step-down, or TSD, procedures) as a
      parametric subclass. We show that all procedures in this class satisfying the
      natural condition of monotonicity and controlling the family-wise error rate
      (FWER) at a prescribed level are dominated by one of them - the classical Holm
      procedure. This generalizes an earlier result pertaining to the subclass of TSD
      procedures (Lehmann and Romano, Testing Statistical Hypotheses, 3rd ed., 2005).
      We also derive a relation between the levels at which a monotone step-down
      procedure controls the FWER and the generalized FWER (the probability of k or
      more false rejections).

PMID- 19759805
TI  - Convenient Synthesis of Acetonide Protected 3,4-Dihydroxyphenylalanine (DOPA) for
      Fmoc Solid-Phase Peptide Synthesis.
AB  - We report a facile approach to the synthesis of acetonide and Fmoc protected 3,4
      dihydroxyphenylalanine (DOPA), Fmoc-DOPA(acetonide)-OH. By protecting the amino
      group of DOPA with a phthaloyl group and the carboxyl group as a methyl ester,
      acetonide protection of the catechol of DOPA derivative was realized in the
      presence of p-toluenesulfonic acid. Following removal of protecting groups, the
      intermediate was converted to Fmoc-DOPA(acetonide)-OH, which was successfully
      incorporated into a short DOPA-containing peptide, derived from marine tubeworm
      cement proteins Pc1 and Pc2.

PMID- 19759806
TI  - Laser-Machined Shape Memory Alloy Sensors for Position Feedback in Active
      Catheters.
AB  - Catheter-based interventions are a form of minimally invasive surgery that can
      decrease hospitalization time and greatly lower patient morbidity compared to
      traditional methods. However, percutaneous catheter procedures are hindered by a
      lack of precise tip manipulation when actuation forces are transmitted over the
      length of the catheter. Active catheters with local shape-memory-alloy (SMA)
      actuation can potentially provide the desired manipulation of a catheter tip, but
      hysteresis makes it difficult to control the actuators. A method to integrate
      small-volume, compliant sensors on an active catheter to provide position
      feedback for control would greatly improve the viability of SMA-based active
      catheters. In this work, we describe the design, fabrication, and performance of
      resistance-based position sensors that are laser-machined from superelastic SMA
      tubing. Combining simple material models and rapid prototyping, we can develop
      sensors of appropriate stiffness and sensitivity with simple modifications in
      sensor geometry. The sensors exhibit excellent linearity over the operating range
      and are designed to be easily integrated onto an active catheter substrate.

PMID- 19759807
TI  - Optimal minimax designs over a prespecified interval in a heteroscedastic
      polynomial model.
AB  - Minimax optimal designs can be useful for estimating response surface but they
      are notoriously difficult to study analytically. We provide formulae for three
      types of minimax optimal designs over a user-specified region. We focus on
      polynomial models with various types of heteroscedastic errors but the design
      strategy is applicable to other types of linear models and optimality criteria.
      Relationships among the three types of minimax optimal designs are discussed.

PMID- 19759808
TI  - Identification of differentially expressed spatial clusters using humoral
      response microarray data.
AB  - The antibody microarray is a powerful chip-based technology for profiling
      hundreds of proteins simultaneously and is used increasingly nowadays. To study
      humoral response in pancreatic cancers, Patwa et al. (2007) developed a two
      dimensional liquid separation technique and built a two-dimensional antibody
      microarray. However, identifying differential expression regions on the antibody
      microarray requires the use of appropriate statistical methods to fairly assess
      the large amounts of data generated. In this paper, we propose a permutation
      based test using spatial information of the two-dimensional antibody microarray.
      By borrowing strength from the neighboring differentially expressed spots, we are
      able to detect the differential expression region with very high power
      controlling type I error at 0.05 in our simulation studies. We also apply the
      proposed methodology to a real microarray dataset.

PMID- 19759809
TI  - Analysis of protein chameleon sequence characteristics.
AB  - Conversion of local structural state of a protein from an alpha-helix to a beta
      strand is usually associated with a major change in the tertiary structure.
      Similar changes were observed during the self assembly of amyloidogenic proteins
      to form fibrils, which are implicated in severe diseases conditions, e.g.,
      Alzheimer disease. Studies have emphasized that certain protein sequence
      fragments known as chameleon sequences do not have a strong preference for either
      helical or the extended conformations. Surprisingly, the information on the local
      sequence neighborhood can be used to predict their secondary at a high accuracy
      level. Here we report a large scale-analysis of chameleon sequences to estimate
      their propensities to be associated with different local structural states such
      as alpha -helices, beta-strands and coils. With the help of the propensity
      information derived from the amino acid composition, we underline their
      complexity, as more than one quarter of them prefers coil state over to the
      regular secondary structures. About half of them show preference for both alpha
      helix and beta-sheet conformations and either of these two states is favored by
      the rest.

PMID- 19759810
TI  - A putative nuclear growth factor-like globular nematode specific protein.
AB  - Expressed sequence tags (ESTs) are an effective approach for discovery of novel
      genes. In the current study, approximately 250 ESTs of the cattle parasitic
      nematode Setaria digitata were examined and a cDNA clone identified whose coding
      sequence could not be functionally annotated by searching over publicly available
      genome, protein, EST and STS databases. Here, we report the extensive
      characterization of this ORF (UP) and its homologues using a bioinformatic
      approach. Uncharacterized protein (SDUP) of S. digitata consists of 204 amino
      acids with a predicted molecular weight and isoelectric point of 22.8KDa and
      9.94, respectively. A search carried out using SDUP over nucleotide, EST and
      protein databases at NCBI, NEMBASE3 and Parasite Genome Database (PGD) identified
      homologous counterparts from the human parasitic nematodes Wuchereria bancrofti
      (WB), Brugia malayi (BM), Onchocerca volvulus (OV), the mouse filarial worm
      Litomosoides sigmodontis (LS), swine parasitic nematodes Ascaris suum (AS) and
      diverged counterparts from the plant parasitic nematode Meloidogyne hapla (MH)
      and free living nematodes Caenorhabditis elegans (CE) and Caenorhabditis briggsae
      (CB). Phylogenetic analyses revealed the UPs to be undergoing divergent
      evolution. A search of the ESTs at PGD showed that UP is expressed in all the
      stages of BM. Secondary structure analyses of multiply-aligned sequences of
      homologues using Jpred server indicated UPs to be rich in beta-pleated
      structures. TMMHH server and beta barrel finder programme indicated, UPs to be
      neither transmembrane or beta barrels proteins but are likely to be globular
      proteins. Further, the Motif discovery tool of MEME identified three novel
      potential motifs for UPS, of which only two are present in CE, CB & MH. Analyses
      of UPs using Signal IP, TargetP, Psort servers predicted this group of proteins
      to be devoid of signal peptide cleavage sites, are not mitochondrial targeting
      peptides but appear to be localized to the nucleus, respectively. Further
      analyses of the UPs using ScanProsite server for phosphorylation revealed
      potential sites for cAMP- and cGMP-dependent protein kinase, Protein kinase C and
      Casein kinase II. Putative functional analysis using ProtFun 2.1 Server indicated
      UPs to be nonenzymatic, growth factor like protein. Finally, collating all the
      information derived from bioinformatic analyses, we conclude that the UPs of
      nematodes are most likely to be expressed at all stages in the life cycle,
      localized to the nucleus, regulated by phosphorylation, rich in beta-pleated
      strands and are growth factor like nematode specific proteins.

PMID- 19759811
TI  - Regulatory elements in the 5'region of 16SrRNA gene of Bacillus sp. strain SJ
      101.
AB  - Advancement in bioinformatics with the development of computational tools has
      enabled the in-silico prediction and identification of transcription regulatory
      factors and other genetic elements with great ease. In this study, computational
      analysis of sequence homology of 546 bp 5' region of 16SrRNA gene of Bacillus sp.
      strain SJ-101 resulted in identification of promoter-like sequences within the
      rrn gene. Using BPROM tool, the regulatory motifs like -35 and -10 boxes were
      mapped at 392 and 411 positions, respectively. Furthermore, the cis-acting
      elements as the binding sites for transcription factors (TF) cpxR and argR were
      identified at positions 413 and 416 at the upstream of an open reading frame
      (ORF). The probable functions of the putative TFs were predicted through the Uni
      Prot/Swiss-Prot protein database. Search for the Shine-Dalgarno sequence (SD)
      found the presence of highly conserved SD sequence (AATACC), and a short 42 bp
      coding sequence/ORF bounded with characteristic transcription start site (AAC)
      and a stop codon (TGA) at positions 426 and 465 downstream to the promoter
      elements. A 13 amino acid long translation product of a short ORF has exhibited
      100% homology with protein sequences of Bacillus spp., while showing some degree
      of polymorphism with other reference strains. The comparative homology of the
      small protein exhibited maximum similarity with Prolyl-4 hydroxylase of
      Chlamydomonas reinhardtii with 4.11 ZSCORE. The highly conserved regulatory
      elements and the putative ORF predicted within the 16SrRNA gene may help
      understand the role of relatively unexplored short ORFs within rrn operon, and
      their functional products in genetic regulatory mechanisms in eubacteria.

PMID- 19759812
TI  - Identification of Comamonas species using 16S rRNA gene sequence.
AB  - A bacterial strain Bz02 was isolated from a water sample collected from river
      Gomti at the Indian city of Lucknow. We characterized the strain using 16S rRNA
      sequence. Phylogenetic analysis showed that the strain formed a monophyletic
      clade with members of the genus Comamonas. The closest phylogenetic relative was
      Comamonas testosteroni with 95% 16S rRNA gene sequence similarity. It is proposed
      that the identified strain Bz02 be assigned as the type strain of a species of
      the genus Comamonas (Comamonas sp Bz02) based on 16S rRNA gene sequence search in
      Ribosomal Database Project, small subunit rRNA and large subunit rRNA databases
      together with the phylogenetic tree analysis. The sequence is deposted in GenBank
      with the accession number FJ211417.

PMID- 19759813
TI  - A simple approach discriminating cardio-safe drugs from toxic ones.
AB  - More than 130 FDA-approved drugs have been identified for now to prolong the QT
      interval and possibly lead to sudden cardiac death. Due to their toxic effect,
      some of these drugs have been withdrawn from the pharmaceutical market. In this
      study, we have formulated few rules to assess the ability to prolong QT interval
      and thereby discriminate between cardiotoxic and -safe drugs. These rules have
      clearly determined that cardio-toxic drugs are more likely to obey Lipinski rule
      of 5 and Oprea lead-like rule. Moreover, the cardio-toxic drugs have been found
      to have in common values of -0.5 to 6.5 log P, 1-5 nitrogen atoms, up to 4 oxygen
      atoms, 5-27 hydrophobic atoms, and 15-53 single bonds. Matthews Correlation
      Coefficient with the value of 0.6 was also attained and nearly 96% of the cardio
      toxic drugs were successfully covered. Thus, despite the simplicity of this
      methodology, we have obtained interesting and informative results. The proposed
      set of these simple rules could be employed to infer cardio-toxicity or -safety
      for current and potential drugs. The present study will have important impact on
      decision making in the fields of drug development, molecule screening in
      biological assays, and other applications as well.

PMID- 19759814
TI  - A molecular model for diacylglycerol acyltransferase from Mortierella ramanniana
      var. angulispora.
AB  - Acyl CoA diacylglycerol acyltransferase (DGAT, EC 2.3.120) is recognized as a key
      player of cellular diacylglycerol metabolism. It catalyzes the terminal, yet the
      committed step in triacylglycerol synthesis using diacylglycerol and fatty acyl
      CoA as substrates. The protein sequence of diacylglycerol acyltransferse (DGAT)
      Type 2B in Moretierella ramanniana var. angulispora (Protein_ID = AAK84180.1) was
      retrieved from GenBank. However, a structure is not yet available for this
      sequence. The 3D structure of DGAT Type 2B was modeled using a template structure
      (PDB ID: 1K30) obtained from Protein databank (PDB) identified by searching with
      position specific iterative BLAST (PSI-BLAST). The template (PDB ID: 1K30)
      describes the structure of DGAT from Cucurbita moschata. Modeling was performed
      using Modeller 9v2 and protein model is hence generated. The DGAT type 2B protein
      model was subsequently docked with six inhibitors (sphingosine;
      trifluoroperazine; phosphatidic acid; lysophospatidylserine; KCl; 1, 2-diolein)
      using AutoDock (a molecular docking program). The binding of inhibitors to the
      protein model of DGAT type 2B is discussed.

PMID- 19759815
TI  - Abyssinones and related flavonoids as potential steroidogenesis modulators.
AB  - Abyssinones and related flavonoids were screened against 3 enzymes (3betaHSD,
      17betaHSD and Aromatase) of steroidogenesis pathway. The virtual screening
      experiment shows high affinity for flavonones than their respective chalcones. A
      4' -OH blocked prenylated flavonone 2b (2-(2', 2'-dimethyl chroman-6'-yl)-7
      hydroxy chroman-4-one) had consistent binding affinity to all the three enzymes
      used in this study showing higher binding affinity to aromatase. A good
      correlation was observed between cytotoxic data (MCF-7, breast cancer cell line)
      and docking results indicating flavonone as a better steroidogenesis modulator in
      hormone dependent cancer.

PMID- 19759816
TI  - Prediction of MHC class I binding peptides using probability distribution
      functions.
AB  - Binding of peptides to specific Major Histo-compatibility Complex (MHC) molecule
      is important for understanding immunity and has applications to vaccine discovery
      and design of immunotherapy. Artificial neural networks (ANN) are widely used by
      predictions tools to classify the peptides as binders or non-binders (BNB).
      However, the number of known binders to a specific MHC molecule is limited in
      many cases, which poses a computational challenge for prediction of BNB and
      hence, needs improvement in learning of ANN. Here, we describe, the application
      of probability distribution functions to initialize the weights and biases of the
      artificial neural network in order to predict HLA-A*0201 binders and non-binders.
      The 10-fold cross validation has been used to validate the results. It is evident
      from the results that the A(ROC) for 90% of test cases for Weibull, Uniform and
      Rayleigh distributions is in the range 0.90-1.0. Further, the standard deviation
      for AROC was minimum for Weibull distribution, and may be used to train the
      artificial neural network for HLA-A*0201 MHC Class-I binders and non-binders
      prediction.

PMID- 19759817
TI  - Role of large hydrophobic residues in proteins.
AB  - Large Hydrophobic Residues (LHR) such as phenylalanine, isoleucine, leucine,
      methionine and valine play an important role in protein structure and activity.
      We describe the role of LHR in complete set of protein sequences in 15 different
      species. That is the distribution of LHR in different proteins of different
      species is reported. It is observed that the proteins prefer to have 27% of large
      hydrophobic residues in total and all along the sequence. It is also observed
      that proteins accumulate more LHR in its active sites. A window analysis on these
      protein sequences shows that the 27% of LHR is more frequent at window length of
      45 amino acids. The influenza virus and P. falciparum show a random distribution
      of LHR in its proteins compared to other model organisms.

PMID- 19759818
TI  - A non-humanoid robot in the "uncanny valley": experimental analysis of the
      reaction to behavioral contingency in 2-3 year old children.
AB  - Infants' sensitivity to social or behavioral contingency has been examined in the
      field of developmental psychology and behavioral sciences, mainly using a double
      video paradigm or a still face paradigm. These studies have shown that infants
      distinguish other individuals' contingent behaviors from non-contingent ones. The
      present experiment systematically examined if this ability extends to the
      detection of non-humanoids' contingent actions in a communicative context. We
      examined two- to three-year-olds' understanding of contingent actions produced by
      a non-humanoid robot. The robot either responded contingently to the actions of
      the participants (contingent condition) or programmatically reproduced the same
      sequence of actions to another participant (non-contingent condition). The
      results revealed that the participants exhibited different patterns of response
      depending on whether or not the robot responded contingently. It was also found
      that the participants did not respond positively to the contingent actions of the
      robot in the earlier periods of the experimental sessions. This might reflect the
      conflict between the non-humanlike appearance of the robot and its humanlike
      contingent actions, which presumably led the children to experience the uncanny
      valley effect.

PMID- 19759819
TI  - Spatial distribution of human Schistosoma japonicum infections in the Dongting
      Lake Region, China.
AB  - BACKGROUND: The aim of this study was to spatially model the effect of
      demographic, reservoir hosts and environmental factors on human Schistosoma
      japonicum infection prevalence in the Dongting Lake area of Hunan Province, China
      and to determine the potential of each indicator in targeting schistosomiasis
      control. METHODOLOGY/PRINCIPAL FINDINGS: Cross-sectional serological,
      coprological and demographic data were obtained from the 2004 nationwide periodic
      epidemiologic survey for Hunan Province. Environmental data were downloaded from
      the USGS EROS data centre. Bayesian geostatistical models were employed for
      spatial analysis of the infection prevalence among study participants. A total of
      47,139 participants from 47 administrative villages were selected. Age, sex and
      occupation of residents and the presence of infected buffaloes and environmental
      factors, i.e. NDVI, distance to the lake and endemic type of setting, were
      significantly associated with S. japonicum infection prevalence. After taking
      into account spatial correlation, however, only demographic factors (age, sex and
      occupation) and the presence of infected buffaloes remained significant
      indicators. CONCLUSIONS/SIGNIFICANCE: Long established demographic factors, as
      well presence of host reservoirs rather than environmental factors are driving
      human transmission. Findings of this work can be used for epidemiologic
      surveillance and for the future planning of interventions in the Dongting Lake
      area of Hunan Province.

PMID- 19759820
TI  - The NlpD lipoprotein is a novel Yersinia pestis virulence factor essential for
      the development of plague.
AB  - Yersinia pestis is the causative agent of plague. Previously we have isolated an
      attenuated Y. pestis transposon insertion mutant in which the pcm gene was
      disrupted. In the present study, we investigated the expression and the role of
      pcm locus genes in Y. pestis pathogenesis using a set of isogenic surE, pcm, nlpD
      and rpoS mutants of the fully virulent Kimberley53 strain. We show that in Y.
      pestis, nlpD expression is controlled from elements residing within the upstream
      genes surE and pcm. The NlpD lipoprotein is the only factor encoded from the pcm
      locus that is essential for Y. pestis virulence. A chromosomal deletion of the
      nlpD gene sequence resulted in a drastic reduction in virulence to an LD(50) of
      at least 10(7) cfu for subcutaneous and airway routes of infection. The mutant
      was unable to colonize mouse organs following infection. The filamented
      morphology of the nlpD mutant indicates that NlpD is involved in cell separation;
      however, deletion of nlpD did not affect in vitro growth rate. Trans
      complementation experiments with the Y. pestis nlpD gene restored virulence and
      all other phenotypic defects. Finally, we demonstrated that subcutaneous
      administration of the nlpD mutant could protect animals against bubonic and
      primary pneumonic plague. Taken together, these results demonstrate that Y.
      pestis NlpD is a novel virulence factor essential for the development of bubonic
      and pneumonic plague. Further, the nlpD mutant is superior to the EV76 prototype
      live vaccine strain in immunogenicity and in conferring effective protective
      immunity. Thus it could serve as a basis for a very potent live vaccine against
      bubonic and pneumonic plague.

PMID- 19759821
TI  - Solution behavior and activity of a halophilic esterase under high salt
      concentration.
AB  - BACKGROUND: Halophiles are extremophiles that thrive in environments with very
      high concentrations of salt. Although the salt reliance and physiology of these
      extremophiles have been widely investigated, the molecular working mechanisms of
      their enzymes under salty conditions have been little explored.
      METHODOLOGY/PRINCIPAL FINDINGS: A halophilic esterolytic enzyme LipC derived from
      archeaon Haloarcula marismortui was overexpressed from Escherichia coli BL21. The
      purified enzyme showed a range of hydrolytic activity towards the substrates of p
      nitrophenyl esters with different alkyl chains (n = 2-16), with the highest
      activity being observed for p-nitrophenyl acetate, consistent with the basic
      character of an esterase. The optimal esterase activities were found to be at pH
      9.5 and [NaCl] = 3.4 M or [KCl] = 3.0 M and at around 45 degrees C.
      Interestingly, the hydrolysis activity showed a clear reversibility against
      changes in salt concentration. At the ambient temperature of 22 degrees C, enzyme
      systems working under the optimal salt concentrations were very stable against
      time. Increase in temperature increased the activity but reduced its stability.
      Circular dichroism (CD), dynamic light scattering (DLS) and small angle neutron
      scattering (SANS) were deployed to determine the physical states of LipC in
      solution. As the salt concentration increased, DLS revealed substantial increase
      in aggregate sizes, but CD measurements revealed the maximal retention of the
      alpha-helical structure at the salt concentration matching the optimal activity.
      These observations were supported by SANS analysis that revealed the highest
      proportion of unimers and dimers around the optimal salt concentration, although
      the coexistent larger aggregates showed a trend of increasing size with salt
      concentration, consistent with the DLS data. CONCLUSIONS/SIGNIFICANCE: The
      solution alpha-helical structure and activity relation also matched the highest
      proportion of enzyme unimers and dimers. Given that all the solutions studied
      were structurally inhomogeneous, it is important for future work to understand
      how the LipC's solution aggregation affected its activity.

PMID- 19759822
TI  - Major role of microbes in carbon fluxes during Austral winter in the Southern
      Drake Passage.
AB  - Carbon cycling in Southern Ocean is a major issue in climate change, hence the
      need to understand the role of biota in the regulation of carbon fixation and
      cycling. Southern Ocean is a heterogeneous system, characterized by a strong
      seasonality, due to long dark winter. Yet, currently little is known about
      biogeochemical dynamics during this season, particularly in the deeper part of
      the ocean. We studied bacterial communities and processes in summer and winter
      cruises in the southern Drake Passage. Here we show that in winter, when the
      primary production is greatly reduced, Bacteria and Archaea become the major
      producers of biogenic particles, at the expense of dissolved organic carbon
      drawdown. Heterotrophic production and chemoautotrophic CO(2) fixation rates were
      substantial, also in deep water, and bacterial populations were controlled by
      protists and viruses. A dynamic food web is also consistent with the observed
      temporal and spatial variations in archaeal and bacterial communities that might
      exploit various niches. Thus, Southern Ocean microbial loop may substantially
      maintain a wintertime food web and system respiration at the expense of summer
      produced DOC as well as regenerate nutrients and iron. Our findings have
      important implications for Southern Ocean ecosystem functioning and carbon cycle
      and its manipulation by iron enrichment to achieve net sequestration of
      atmospheric CO(2).

PMID- 19759823
TI  - Design parameters to control synthetic gene expression in Escherichia coli.
AB  - BACKGROUND: Production of proteins as therapeutic agents, research reagents and
      molecular tools frequently depends on expression in heterologous hosts. Synthetic
      genes are increasingly used for protein production because sequence information
      is easier to obtain than the corresponding physical DNA. Protein-coding sequences
      are commonly re-designed to enhance expression, but there are no experimentally
      supported design principles. PRINCIPAL FINDINGS: To identify sequence features
      that affect protein expression we synthesized and expressed in E. coli two sets
      of 40 genes encoding two commercially valuable proteins, a DNA polymerase and a
      single chain antibody. Genes differing only in synonymous codon usage expressed
      protein at levels ranging from undetectable to 30% of cellular protein. Using
      partial least squares regression we tested the correlation of protein production
      levels with parameters that have been reported to affect expression. We found
      that the amount of protein produced in E. coli was strongly dependent on the
      codons used to encode a subset of amino acids. Favorable codons were
      predominantly those read by tRNAs that are most highly charged during amino acid
      starvation, not codons that are most abundant in highly expressed E. coli
      proteins. Finally we confirmed the validity of our models by designing,
      synthesizing and testing new genes using codon biases predicted to perform well.
      CONCLUSION: The systematic analysis of gene design parameters shown in this study
      has allowed us to identify codon usage within a gene as a critical determinant of
      achievable protein expression levels in E. coli. We propose a biochemical basis
      for this, as well as design algorithms to ensure high protein production from
      synthetic genes. Replication of this methodology should allow similar design
      algorithms to be empirically derived for any expression system.

PMID- 19759824
TI  - Glutamic acid decarboxylase-derived epitopes with specific domains expand
      CD4(+)CD25(+) regulatory T cells.
AB  - BACKGROUND: CD4(+)CD25(+) regulatory T cell (Treg)-based immunotherapy is
      considered a promising regimen for controlling the progression of autoimmune
      diabetes. In this study, we tested the hypothesis that the therapeutic effects of
      Tregs in response to the antigenic epitope stimulation depend on the structural
      properties of the epitopes used. METHODOLOGY/PRINCIPAL FINDINGS: Splenic
      lymphocytes from nonobese diabetic (NOD) mice were stimulated with different
      glutamic acid decarboxylase (GAD)-derived epitopes for 7-10 days and the
      frequency and function of Tregs was analyzed. We found that, although all
      expanded Tregs showed suppressive functions in vitro, only p524 (GAD524-538)
      expanded CD4(+)CD25(+) T cells inhibited diabetes development in the co-transfer
      models, while p509 (GAD509-528)- or p530 (GAD530-543)-expanded CD4(+)CD25(+) T
      cells had no such effects. Using computer-guided molecular modeling and docking
      methods, the differences in structural characteristics of these epitopes and the
      interaction mode (including binding energy and identified domains in the
      epitopes) between the above-mentioned epitopes and MHC class II I-A(g7) were
      analyzed. The theoretical results showed that the epitope p524, which induced
      protective Tregs, possessed negative surface-electrostatic potential and bound
      two chains of MHC class II I-A(g7), while the epitopes p509 and p530 which had no
      such ability exhibited positive surface-electrostatic potential and bound one
      chain of I-A(g7). Furthermore, p524 bound to I-A(g7) more stably than p509 and
      p530. Of importance, we hypothesized and subsequently confirmed experimentally
      that the epitope (GAD570-585, p570), which displayed similar characteristics to
      p524, was a protective epitope by showing that p570-expanded CD4(+)CD25(+) T
      cells suppressed the onset of diabetes in NOD mice. CONCLUSIONS/SIGNIFICANCE:
      These data suggest that molecular modeling-based structural analysis of epitopes
      may be an instrumental tool for prediction of protective epitopes to expand
      functional Tregs.

PMID- 19759825
TI  - The Schizosaccharomyces pombe Hsp104 disaggregase is unable to propagate the
      [PSI] prion.
AB  - The molecular chaperone Hsp104 is a crucial factor in the acquisition of
      thermotolerance in yeast. Under stress conditions, the disaggregase activity of
      Hsp104 facilitates the reactivation of misfolded proteins. Hsp104 is also
      involved in the propagation of fungal prions. For instance, the well
      characterized [PSI(+)] prion of Saccharomyces cerevisiae does not propagate in
      Deltahsp104 cells or in cells overexpressing Hsp104. In this study, we
      characterized the functional homolog of Hsp104 from Schizosaccharomyces pombe
      (Sp_Hsp104). As its S. cerevisiae counterpart, Sp_hsp104(+) is heat-inducible and
      required for thermotolerance in S. pombe. Sp_Hsp104 displays low disaggregase
      activity and cannot propagate the [PSI(+)] prion in S. cerevisiae. When
      overexpressed in S. cerevisiae, Sp_Hsp104 confers thermotolerance to Deltahsp104
      cells and reactivates heat-aggregated proteins. However, overexpression of
      Sp_Hsp104 does not propagate nor eliminate [PSI(+)]. Strikingly, [PSI(+)] was
      cured by overexpression of a chimeric chaperone bearing the C-terminal domain
      (CTD) of the S. cerevisiae Hsp104 protein. Our study demonstrates that the
      ability to untangle aggregated proteins is conserved between the S. pombe and S.
      cerevisiae Hsp104 homologs, and points to a role of the CTD in the propagation of
      the S. cerevisiae [PSI(+)] prion.

PMID- 19759826
TI  - Histidine residue 94 is involved in pH sensing by histidine kinase ArsS of
      Helicobacter pylori.
AB  - BACKGROUND: The ArsRS two-component system is the master regulator of acid
      adaptation in the human gastric pathogen Helicobacter pylori. Low pH is supposed
      to trigger the autophosphorylation of the histidine kinase ArsS and the
      subsequent transfer of the phosphoryl group to its cognate response regulator
      ArsR which then acts as an activator or repressor of pH-responsive genes.
      Orthologs of the ArsRS two-component system are also present in H. pylori's close
      relatives H. hepaticus, Campylobacter jejuni and Wolinella succinogenes which are
      non-gastric colonizers. METHODOLOGY/PRINCIPAL FINDINGS: In order to investigate
      the mechanism of acid perception by ArsS, derivatives of H. pylori 26695
      expressing ArsS proteins with substitutions of the histidine residues present in
      its periplasmic input domain were constructed. Analysis of pH-responsive
      transcription of selected ArsRS target genes in these mutants revealed that H94
      is relevant for pH sensing, however, our data indicate that protonatable amino
      acids other than histidine contribute substantially to acid perception by ArsS.
      By the construction and analysis of H. pylori mutants carrying arsS allels from
      the related epsilon-proteobacteria we demonstrate that WS1818 of W. succinogenes
      efficiently responds to acidic pH. CONCLUSIONS/SIGNIFICANCE: We show that H94 in
      the input domain of ArsS is crucial for acid perception in H. pylori 26695. In
      addition our data suggest that ArsS is able to adopt different conformations
      depending on the degree of protonation of acidic amino acids in the input domain.
      This might result in different activation states of the histidine kinase allowing
      a gradual transcriptional response to low pH conditions. Although retaining
      considerable similarity to ArsS the orthologous proteins of H. hepaticus and C.
      jejuni may have evolved to sensors of a different environmental stimulus in
      accordance with the non gastric habitat of these bacteria.

PMID- 19759827
TI  - High efficiency lipid-based siRNA transfection of adipocytes in suspension.
AB  - BACKGROUND: Fully differentiated adipocytes are considered to be refractory to
      introduction of siRNA via lipid-based transfection. However, large scale siRNA
      based loss-of-function screening of adipocytes using either electroporation or
      virally-mediated transfection approaches can be prohibitively complex and
      expensive. METHODOLOGY/PRINCIPAL FINDINGS: We present a method for introducing
      small interfering RNA (siRNA) into differentiated 3T3-L1 adipocytes and primary
      human adipocytes using an approach based on forming the siRNA/cell complex with
      the adipocytes in suspension rather than as an adherent monolayer, a variation of
      "reverse transfection". CONCLUSIONS/SIGNIFICANCE: Transfection of adipocytes with
      siRNA by this method is economical, highly efficient, has a simple workflow, and
      allows standardization of the ratio of siRNA/cell number, making this approach
      well-suited for high-throughput screening of fully differentiated adipocytes.

PMID- 19759828
TI  - Earlier onset of delta-retrovirus-induced leukemia after splenectomy.
AB  - Infection by delta-retroviruses such as human T-lymphotropic virus type 1 (HTLV
      1) and bovine leukemia virus (BLV) is mostly asymptomatic. Indeed, only a
      minority (<5%) of delta-retrovirus infected hosts will develop either
      lymphoproliferative or neurodegenerative diseases after long latency periods. In
      fact, the host immune response is believed to tightly control viral replication
      but this assumption has not been definitely proven in vivo. Here, we provide
      direct experimental evidence demonstrating that integrity of the spleen is
      required to control pathogenesis. In the BLV model, we show that asplenia
      decreases efficiency of the immune response and induces an imbalance in cell
      dynamics resulting in accelerated onset of leukemia. These observations enlighten
      a potential threat in splenectomized HTLV-1 carriers and justify a regular
      preventive evaluation.

PMID- 19759829
TI  - Genomic analysis suggests that mRNA destabilization by the microprocessor is
      specialized for the auto-regulation of Dgcr8.
AB  - BACKGROUND: The Microprocessor, containing the RNA binding protein Dgcr8 and
      RNase III enzyme Drosha, is responsible for processing primary microRNAs to
      precursor microRNAs. The Microprocessor regulates its own levels by cleaving
      hairpins in the 5'UTR and coding region of the Dgcr8 mRNA, thereby destabilizing
      the mature transcript. METHODOLOGY/PRINCIPAL FINDINGS: To determine whether the
      Microprocessor has a broader role in directly regulating other coding mRNA
      levels, we integrated results from expression profiling and ultra high-throughput
      deep sequencing of small RNAs. Expression analysis of mRNAs in wild-type, Dgcr8
      knockout, and Dicer knockout mouse embryonic stem (ES) cells uncovered mRNAs that
      were specifically upregulated in the Dgcr8 null background. A number of these
      transcripts had evolutionarily conserved predicted hairpin targets for the
      Microprocessor. However, analysis of deep sequencing data of 18 to 200nt small
      RNAs in mouse ES, HeLa, and HepG2 indicates that exonic sequence reads that map
      in a pattern consistent with Microprocessor activity are unique to Dgcr8.
      CONCLUSION/SIGNIFICANCE: We conclude that the Microprocessor's role in directly
      destabilizing coding mRNAs is likely specifically targeted to Dgcr8 itself,
      suggesting a specialized cellular mechanism for gene auto-regulation.

PMID- 19759830
TI  - Evidence for limited genetic compartmentalization of HIV-1 between lung and
      blood.
AB  - BACKGROUND: HIV-1 is frequently detected in the lungs of infected individuals and
      is likely important in the development of pulmonary opportunistic infections. The
      unique environment of the lung, rich in alveolar macrophages and with specialized
      local immune responses, may contribute to differential evolution or selection of
      HIV-1. METHODOLOGY AND FINDINGS: We characterized HIV-1 in the lung in relation
      to contemporaneous viral populations in the blood. The C2-V5 region of HIV-1 env
      was sequenced from paired lung (induced sputum or bronchoalveolar lavage) and
      blood (plasma RNA and proviral DNA from sorted or unsorted PBMC) from 18
      subjects. Compartmentalization between tissue pairs was assessed using 5
      established tree or distance-based methods, including permutation tests to
      determine statistical significance. We found statistical evidence of
      compartmentalization between lung and blood in 10/18 subjects, although lung and
      blood sequences were intermingled on phylogenetic trees in all subjects. The
      subject showing the greatest compartmentalization contained many nearly identical
      sequences in BAL sample, suggesting clonal expansion may contribute to reduced
      viral diversity in the lung in some cases. However, HIV-1 sequences in lung were
      not more homogeneous overall, nor were we able to find a lung-specific genotype
      associated with macrophage tropism in V3. In all four subjects in whom predicted
      X4 genotypes were found in blood, predicted X4 genotypes were also found in lung.
      CONCLUSIONS: Our results support a picture of continuous migration of HIV-1
      between circulating blood and lung tissue, with perhaps a very limited degree of
      localized evolution or clonal replication.

PMID- 19759831
TI  - First things first: effectiveness and scalability of a basic prehospital trauma
      care program for lay first-responders in Kampala, Uganda.
AB  - BACKGROUND: We previously showed that in the absence of a formal emergency
      system, lay people face a heavy burden of injuries in Kampala, Uganda, and we
      demonstrated the feasibility of a basic prehospital trauma course for lay people.
      This study tests the effectiveness of this course and estimates the costs and
      cost-effectiveness of scaling up this training. METHODS AND FINDINGS: For six
      months, we prospectively followed 307 trainees (police, taxi drivers, and
      community leaders) who completed a one-day basic prehospital trauma care program
      in 2008. Cross-sectional surveys and fund of knowledge tests were used to measure
      their frequency of skill and supply use, reasons for not providing aid, perceived
      utility of the course and kit, confidence in using skills, and knowledge of first
      aid. We then estimated the cost-effectiveness of scaling up the program. At six
      months, 188 (62%) of the trainees were followed up. Their knowledge retention
      remained high or increased. The mean correct score on a basic fund of knowledge
      test was 92%, up from 86% after initial training (n = 146 pairs, p = 0.0016). 97%
      of participants had used at least one skill from the course: most commonly
      haemorrhage control, recovery position and lifting/moving and 96% had used at
      least one first-aid item. Lack of knowledge was less of a barrier and trainees
      were significantly more confident in providing first-aid. Based on cost estimates
      from the World Health Organization, local injury data, and modelling from
      previous studies, the projected cost of scaling up this program was $0.12 per
      capita or $25-75 per life year saved. Key limitations of the study include small
      sample size, possible reporter bias, preliminary local validation of study
      instruments, and an indirect estimate of mortality reduction. CONCLUSIONS: Lay
      first-responders effectively retained knowledge on prehospital trauma care and
      confidently used their first-aid skills and supplies for at least six months. The
      costs of scaling up this intervention to cover Kampala are very modest. This may
      be a cost-effective first step toward developing formal emergency services in
      Uganda other resource-constrained settings. Further research is needed in this
      critical area of trauma care in low-income countries.

PMID- 19759832
TI  - DETECTING DYNAMIC AND GENETIC EFFECTS ON BRAIN STRUCTURE USING HIGH-DIMENSIONAL
      CORTICAL PATTERN MATCHING.
AB  - We briefly describe a set of algorithms to detect and visualize effects of
      disease and genetic factors on the brain. Extreme variations in cortical anatomy,
      even among normal subjects, complicate the detection and mapping of systematic
      effects on brain structure in human populations. We tackle this problem in two
      stages. First, we develop a cortical pattern matching approach, based on
      metrically covariant partial differential equations (PDEs), to associate
      corresponding regions of cortex in an MRI brain image database (N=102 scans).
      Second, these high-dimensional deformation maps are used to transfer within
      subject cortical signals, including measures of gray matter distribution, shape
      asymmetries, and degenerative rates, to a common anatomic template for
      statistical analysis. We illustrate these techniques in two applications: (1)
      mapping dynamic patterns of gray matter loss in longitudinally scanned
      Alzheimer's disease patients; and (2) mapping genetic influences on brain
      structure. We extend statistics used widely in behavioral genetics to cortical
      manifolds. Specifically, we introduce methods based on h-squared distributed
      random fields to map hereditary influences on brain structure in human
      populations.

PMID- 19759833
TI  - Turning Unorganized Points into Contours.
AB  - There are a variety of research applications that require reconstruction of
      objects from unorganized points. In our implementation, we accomplish this task
      in two steps: first by connecting points to contours and then contours to
      objects. We focus on the first step in this paper. We present a Voxel-coding
      algorithm which assembles unorganized points into contours in a straightforward
      and efficient way. First the points are converted into a binary volumetric object
      using simple 3D Voxel-coding starting with voxels that include the sample points.
      Then contours are interpreted as centerlines of cross-sections. The centerlines
      are obtained by using a series of2D Voxel-coding operations.Input points are
      sampled from an unknown object satisfying certain sampling criteria. No
      additional details about the input data are needed. Output contours pass through
      or approximate sample points. The algorithm is tested with several data sets,
      showing its efficiency.

PMID- 19759834
TI  - Sit Down to Float: The Cultural Meaning of Ketamine Use in Hong Kong.
AB  - From the late 1990s onward, ketamine use among young persons in Hong Kong grew
      rapidly becoming the drug of choice. This article examines ketamine's attraction
      in Hong Kong, and in so doing uncover the cultural meaning of ketamine use. The
      analysis is organized around the emergence and shifts in meanings and experiences
      of those who initiate and continue to use ketamine. The data stems from a
      comparative study of the social setting of club drug use in Hong Kong, San
      Francisco, and Rotterdam. Here we draw from 100 in-depth interviews to examine
      the experiences of young persons who have used drugs in dance venues in Hong
      Kong. Our findings indicate that ketamine has become embedded in a distinctively
      working class youth dance scene, is accessible in terms of supply and cost,
      shared among a group of friends, and results in a stimulating yet liberating
      experience beyond that of ecstasy.

PMID- 19759835
TI  - Mapping Ancient Forests: Bayesian Inference for Spatio-temporal Trends in Forest
      Composition Using the Fossil Pollen Proxy Record.
AB  - Ecologists use the relative abundance of fossil pollen in sediments to estimate
      how tree species abundances change over space and time. To predict historical
      forest composition and quantify the available information, we build a Bayesian
      hierarchical model of forest composition in central New England, USA, based on
      pollen in a network of ponds. The critical relationships between abundances of
      taxa in the pollen record and abundances as actual vegetation are estimated for
      the modern and colonial periods, for which both pollen and direct vegetation data
      are available, based on a latent multivariate spatial process representing forest
      composition. For time periods in the past with only pollen data, we use the
      estimated model parameters to constrain predictions about the latent spatio
      temporal process conditional on the pollen data. We develop an innovative
      graphical assessment of feature significance to help to infer which spatial
      patterns are reliably estimated. The model allows us to estimate the spatial
      distribution and relative abundances of tree species over the last 2500 years,
      with an assessment of uncertainty, and to draw inference about how these patterns
      have changed over time. Cross-validation suggests that our feature significance
      approach can reliably indicate certain large-scale spatial features for many
      taxa, but that features on scales smaller than 50 km are difficult to
      distinguish, as are large-scale features for some taxa. We also use the model to
      quantitatively investigate ecological hypotheses, including covariate effects on
      taxa abundances and questions about pollen dispersal characteristics. The
      critical advantages of our modeling approach over current ecological analyses are
      the explicit spatio-temporal representation, quantification of abundance on the
      scale of trees rather than pollen, and uncertainty characterization.

PMID- 19759836
TI  - Recruiting Urban Latina Adolescents and Their Families: Challenges and Lessons
      Learned in Suicide Attempts Research.
AB  - Recruiting samples with unique characteristics dispersed across services and
      geography is hard to identify because of legal status and stigma create research
      challenges. Public health, however, requires sustained recruitment efforts. We
      describe challenges and solutions in recruiting urban adolescent Latinas who had
      attempted suicide. Procedures for recruitment and human subject protections were
      established, yet logistic obstacles emerged. Program directors failed to support
      the research; therapists were slow to identify subjects and to meet inclusionary
      criteria; numbers of prospective participants were lower than originally
      calculated; girls and parents were hard to reach; and interview appointments were
      missed. From challenges came solutions: to use fewer agencies, do better
      participant surveillance, monitor staff participation, and build rapport and
      relationships with staff. In-service research training to develop agency research
      infrastructure generated support among providers and administrators. Our
      experience may be helpful to other researchers conducting studies with similar
      populations.

PMID- 19759837
TI  - Use of coronal simultaneous optical coherence tomography/scanning laser
      ophthalmoscopy to demonstrate cystoid macular edema secondary to extrafoveal
      retinal hole.
AB  - PURPOSE: To describe a clinical appearance of macular edema secondary to
      extrafoveal retinal hole using coronal (en-face) optical coherence
      tomography/scanning laser ophthalmoscopy (OCT/SLO) imaging. METHOD: Case report.
      RESULTS: A 76-year-old man developed an extrafoveal retinal hole in his right eye
      after pars plana vitrectomy and epiretinal membrane removal 1 year after surgery.
      He complained of decreased central vision. Coronal scan showed extrafoveal
      retinal hole with multiple retinal cysts surrounding the retinal hole and
      communicating with the macular area. CONCLUSION: The OCT/SLO ophthalmoscope can
      be useful in understanding pathophysiology of macular edema.

PMID- 19759838
TI  - Significant analgesic effects of one session of postoperative left prefrontal
      cortex repetitive transcranial magnetic stimulation: a replication study.
AB  - BACKGROUND: In a recent preliminary trial in 20 patients after gastric bypass
      surgery, 20 minutes of repetitive transcranial magnetic stimulation (TMS) over
      the left prefrontal cortex was associated with a 40% reduction in postoperative
      patient-controlled morphine use. As is the case with all novel scientific
      findings, and especially those that might have an impact on clinical practice,
      replicability is paramount. This study sought to test this finding for
      replication and to more accurately estimate the effect size of this brief
      intervention on postoperative morphine use and postoperative pain and mood
      ratings. METHODS: Twenty participants who underwent gastric bypass surgery
      completed this replication and extension study. Beck Depression Inventory and
      Center for Epidemiological Studies Depression scale scores were collected before
      surgery and at the time of discharge from the hospital. Immediately after
      surgery, participants were randomly assigned to receive 20 minutes of real or
      sham repetitive TMS (rTMS) (10 Hz, 10 seconds-ON, 20 seconds-OFF for a total of
      4000 pulses). Patient-controlled morphine pump usage was tracked throughout each
      participant's postoperative hospital stay. In addition, pain and mood ratings
      were collected via visual analogue scales twice per day. RESULTS: Findings from
      the original postoperative TMS trial were replicated, as cumulative morphine
      usage curves were significantly steeper among patients receiving sham TMS, and
      participants receiving real TMS had used 35% less morphine at the time of
      discharge than participants receiving sham TMS. At the time of discharge,
      subjects who had received real TMS had used 42.50 mg of morphine, whereas
      subjects receiving sham TMS had used an average of 64.88 mg. When the data from
      the original preliminary trial were combined with the data from this replication
      trial, a significant difference in cumulative morphine usage was observed between
      subjects receiving real and sham TMS. Overall, participants who received real TMS
      used 36% less morphine and had significantly lower ratings of postoperative pain
      on-average, and pain-at-its-worst than participants receiving sham. In addition,
      participants who received real TMS rated their mood-at-its-worst as significantly
      better than participants receiving sham. The effect of a single 20-minute session
      of TMS on postoperative pain and morphine use appears to be large (Cohen's d =
      0.70) and clinically meaningful. Lastly, cross-lag correlational analyses
      indicate that improvements in mood follow improvements in pain by approximately
      12 hours, supporting the notion that postoperative analgesic TMS effects are not
      driven by antidepressant effects. CONCLUSIONS: Although more research is needed
      to verify these observed effects independently, findings from the original
      postoperative TMS trial were replicated. TMS may have the potential to
      significantly improve current standards of postoperative care among gastric
      bypass patients, and further studies may be warranted on other surgical
      populations. Future investigations should use methodology that permits more
      definitive conclusions about causal effects of TMS on postoperative pain (for
      example, double-blinding, sham stimulation that is matched with real TMS with
      respect to scalp discomfort).

PMID- 19759839
TI  - Flexible Frames and Control Sampling in Case-Control Studies: Weighters (Survey
      Statisticians) Versus Anti-Weighters (Epidemiologists).
AB  - We propose two innovations in statistical sampling for controls to enable better
      design of population-based case-control studies. The main innovation leads to
      novel solutions, without using weights, of the difficult and long-standing
      problem of selecting a control from persons in a household. Another advance
      concerns the drawing (at the outset) of the households themselves and involves
      random-digit dialing with atypical use of list-assisted sampling. A common
      element throughout is that one capitalizes on flexibility (not broadly available
      in usual survey settings) in choosing the frame, which specifies the population
      of persons from which both cases and controls come.

PMID- 19759840
TI  - High Resolution Space-Time Ozone Modeling for Assessing Trends.
AB  - The assessment of air pollution regulatory programs designed to improve ground
      level ozone concentrations is a topic of considerable interest to environmental
      managers. To aid this assessment, it is necessary to model the space-time
      behavior of ozone for predicting summaries of ozone across spatial domains of
      interest and for the detection of long-term trends at monitoring sites. These
      trends, adjusted for the effects of meteorological variables, are needed for
      determining the effectiveness of pollution control programs in terms of their
      magnitude and uncertainties across space. This paper proposes a space-time model
      for daily 8-hour maximum ozone levels to provide input to regulatory activities:
      detection, evaluation, and analysis of spatial patterns of ozone summaries and
      temporal trends. The model is applied to analyzing data from the state of Ohio
      which has been chosen because it contains a mix of urban, suburban, and rural
      ozone monitoring sites in several large cities separated by large rural areas.
      The proposed space-time model is auto-regressive and incorporates the most
      important meteorological variables observed at a collection of ozone monitoring
      sites as well as at several weather stations where ozone levels have not been
      observed. This problem of misalignment of ozone and meteorological data is
      overcome by spatial modeling of the latter. In so doing we adopt an approach
      based on the successive daily increments in meteorological variables. With regard
      to modeling, the increment (or change-in-meteorology) process proves more
      attractive than working directly with the meteorology process, without
      sacrificing any desired inference. The full model is specified within a Bayesian
      framework and is fitted using MCMC techniques. Hence, full inference with regard
      to model unknowns is available as well as for predictions in time and space,
      evaluation of annual summaries and assessment of trends.

PMID- 19759841
TI  - Wavelet-based functional mixed models.
AB  - Increasingly, scientific studies yield functional data, in which the ideal units
      of observation are curves and the observed data consist of sets of curves that
      are sampled on a fine grid. We present new methodology that generalizes the
      linear mixed model to the functional mixed model framework, with model fitting
      done by using a Bayesian wavelet-based approach. This method is flexible,
      allowing functions of arbitrary form and the full range of fixed effects
      structures and between-curve covariance structures that are available in the
      mixed model framework. It yields nonparametric estimates of the fixed and random
      effects functions as well as the various between-curve and within-curve
      covariance matrices. The functional fixed effects are adaptively regularized as a
      result of the non-linear shrinkage prior that is imposed on the fixed effects'
      wavelet coefficients, and the random-effect functions experience a form of
      adaptive regularization because of the separately estimated variance components
      for each wavelet coefficient. Because we have posterior samples for all model
      quantities, we can perform pointwise or joint Bayesian inference or prediction on
      the quantities of the model. The adaptiveness of the method makes it especially
      appropriate for modelling irregular functional data that are characterized by
      numerous local features like peaks.

PMID- 19759842
TI  - Discerning the Division of Cognitive Labor: An Emerging Understanding of How
      Knowledge Is Clustered in Other Minds.
AB  - The division of cognitive labor is fundamental to all cultures. Adults have a
      strong sense of how knowledge is clustered in the world around them and use that
      sense to access additional information, defer to relevant experts, and ground
      their own incomplete understandings. One prominent way of clustering knowledge is
      by disciplines similar to those that comprise the natural and social sciences.
      Seven studies explored an emerging sense of these discipline-based ways of
      clustering of knowledge. Even 5-year-olds could cluster knowledge in a manner
      roughly corresponding to the departments of natural and social sciences in a
      university, doing so without any explicit awareness of those academic
      disciplines. But this awareness is fragile early on and competes with other ways
      of clustering knowledge. Over the next few years, children come to see discipline
      based clusters as having a privileged status, one that may be linked to
      increasingly sophisticated assumptions about essences for natural kinds. Possible
      mechanisms for this developmental shift are examined.

PMID- 19759843
TI  - Tumor spreading to the contralateral ovary in bilateral ovarian carcinoma is a
      late event in clonal evolution.
AB  - Cancer of the ovary is bilateral in 25%. Cytogenetic analysis could determine
      whether the disease in bilateral cases is metastatic or two separately occurring
      primary tumors, but karyotypic information comparing the two cancerous ovaries is
      limited to a single report with 11 informative cases. We present a series of 32
      bilateral ovarian carcinoma cases, analyzed by karyotyping and high-resolution
      CGH. Our karyotypic findings showed that spreading to the contralateral ovary had
      occurred in bilateral ovarian cancer cases and that it was a late event in the
      clonal evolution of the tumors. This was confirmed by the large number of similar
      changes detected by HR-CGH in the different lesions from the same patient. The
      chromosomal bands most frequently involved in structural rearrangements were
      19p13 (n = 12) and 19q13 (n = 11). The chromosomal bands most frequently gained
      by both tumorous ovaries were 5p14 (70%), 8q23-24 (65%), 1q23-24 (57%), and 12p12
      (48%), whereas the most frequently lost bands were 17p11 (78%), 17p13 (74%),
      17p12 (70%), 22q13 (61%), 8p21 and 19q13 (52%), and 8p22-23 (48%). This is the
      first time that 5p14 is seen gained at such a high frequency in cancer of the
      ovary; possibly oncogene(s) involved in bilateral ovarian carcinogenesis or tumor
      progression may reside in this band.

PMID- 19759844
TI  - Discovery and validation of urinary biomarkers for prostate cancer.
AB  - Only 30% of patients with elevated serum prostate specific antigen (PSA) levels
      who undergo prostate biopsy are diagnosed with prostate cancer (PCa). Novel
      methods are needed to reduce the number of unnecessary biopsies. We report on the
      identification and validation of a panel of 12 novel biomarkers for prostate
      cancer (PCaP), using CE coupled MS. The biomarkers could be defined by comparing
      first void urine of 51 men with PCa and 35 with negative prostate biopsy. In
      contrast, midstream urine samples did not allow the identification of
      discriminatory molecules, suggesting that prostatic fluids may be the source of
      the defined biomarkers. Consequently, first void urine samples were tested for
      sufficient amounts of prostatic fluid, using a prostatic fluid indicative panel
      ("informative" polypeptide panel; IPP). A combination of IPP and PCaP to predict
      positive prostate biopsy was evaluated in a blinded prospective study. Two
      hundred thirteen of 264 samples matched the IPP criterion. PCa was detected with
      89% sensitivity, 51% specificity. Including age and percent free PSA to the
      proteomic signatures resulted in 91% sensitivity, 69% specificity.

PMID- 19759845
TI  - Three-Dimensional Microfluidic Tissue-Engineering Scaffolds Using a Flexible
      Biodegradable Polymer.

PMID- 19759846
TI  - Sex differences in responding to rectal  cancer symptoms.
AB  - Many people who develop cancer symptoms wait inordinate amounts of time before
      seeking medical attention. Studies have found that symptom appraisal time--the
      time that passes before the individual concludes that their symptoms could be
      serious--accounts for most of the total delay time across subjects. It is thus
      important to understand the individual characteristics associated with slow
      recognition of dangerous symptoms. In this study, 62 patients (38 males) recently
      diagnosed with rectal cancer answered questions regarding the development of
      symptoms as well as their decisions and behaviors prior to seeking help. One
      subgroup of patients--males with the lowest scores on a measure of trait anxiety-
      took significantly longer to recognize the seriousness of their symptoms as
      compared to all other patients. This finding is discussed in the context of
      recent studies where the interaction of sex and negative affect is related to
      symptom reporting and other health-related behaviors.

PMID- 19759848
TI  - Modifications of DCDHF single molecule fluorophores to impart water solubility.
AB  - A series of dicyanomethylenedihydrofuran (DCDHF) fluorophores with different
      hydrophilic groups were synthesized and their photophysical properties and water
      solubilities were measured. Significant water solubility was achieved without
      compromising desirable photophysical properties, permitting applications of these
      fluorophores in biological systems.

PMID- 19759847
TI  - Proteomic strategies in multiple sclerosis and its animal models.
AB  - The early and precise diagnosis, the prognosis, and the clinical management of
      multiple sclerosis, remain a considerable challenge. In recent years, the
      development of novel and powerful proteomic techniques prompted the use of these
      approaches for the search of unique biomarkers in the cerebrospinal fluid of
      multiple sclerosis patients. A few studies have also utilized proteomics to
      delineate the profile of differentially expressed proteins in animal models of
      the human disease in order to gain global insights into affected pathways. The
      identification of differentially expressed proteins may be an initial step in the
      discovery of novel targets and mechanisms that play critical roles in the
      pathology of multiple sclerosis. Based on these findings, future investigations
      may elucidate the events leading to demyelination, axonal damage, and
      neurodegeneration, providing better insights into mechanisms governing the onset
      and progression of the disease. Although these proteomic studies provide valuable
      information, they are also faced with a number of challenges. The present review
      discusses some of the strengths and limitations of proteomic investigations as
      applied to multiple sclerosis.

PMID- 19759849
TI  - SDU: A Semidefinite Programming-Based Underestimation Method for Stochastic
      Global Optimization in Protein Docking.
AB  - This paper introduces a new stochastic global optimization method targeting
      protein-protein docking problems, an important class of problems in computational
      structural biology. The method is based on finding general convex quadratic
      underestimators to the binding energy function that is funnel-like. Finding the
      optimum underestimator requires solving a semidefinite programming problem, hence
      the name semidefinite programming-based underestimation (SDU). The underestimator
      is used to bias sampling in the search region. It is established that under
      appropriate conditions SDU locates the global energy minimum with probability
      approaching one as the sample size grows. A detailed comparison of SDU with a
      related method of convex global underestimator (CGU), and computational results
      for protein-protein docking problems are provided.

PMID- 19759850
TI  - A splice variant of ASC regulates IL-1beta release and aggregates differently
      from intact ASC.
AB  - The apoptosis-associated speck-like protein containing a caspase recruit domain
      (ASC) is involved in apoptosis and innate immunity and is a major adaptor
      molecule responsible for procaspase-1 activation. ASC mRNA is encoded by three
      exons: exons 1 and 3 encode a pyrin domain (PYD) and caspase recruit domain
      (CARD), respectively, and exon 2 encodes a proline and glycine-rich (PGR) domain.
      Here, we identified a variant ASC protein (vASC) lacking the PGR domain that was
      smaller than full length ASC (fASC) derived from fully transcribed mRNA and
      searched for differences in biochemical and biological nature. Both fASC and vASC
      were found to activate procaspase-1 to a similar degree, but the efficiency of IL
      1beta excretion was significantly higher for vASC. There was also a marked
      structural difference observed in the fibrous aggregates formed by fASC and vASC.
      These results suggest that although the PGR domain is dispensable for procaspase
      1 activation, it plays an important role in the regulation of the molecular
      structure and activity of ASC.

PMID- 19759852
TI  - Heterocyclic amines for the construction of peptoid oligomers bearing multi
      dentate ligands.
AB  - Peptoids are oligomers of N-substituted glycine that can be readily assembled
      using haloacetic acids and primary amines as synthons. Here, we report the
      synthesis and characterization of three new heterocyclic amines, 2-(2,2':6',2''
      terpyridine-4'-yloxy) ethylamine, 2-(1,10-phenanthroline-5-yloxy) ethylamine and
      8-hydroxy-2-quinolinemethylamine, and their incorporation into a series of
      different peptoid oligomer sequences. Since the heterocycles are all known to
      coordinate metal ions, the peptidomimetic products are designed to bind metal
      species with the potential for applications in catalysis and materials science.

PMID- 19759851
TI  - The ataxia (axJ) mutation causes abnormal GABAA receptor turnover in mice.
AB  - Ataxia represents a pathological coordination failure that often involves
      functional disturbances in cerebellar circuits. Purkinje cells (PCs) characterize
      the only output neurons of the cerebellar cortex and critically participate in
      regulating motor coordination. Although different genetic mutations are known
      that cause ataxia, little is known about the underlying cellular mechanisms. Here
      we show that a mutated ax(J) gene locus, encoding the ubiquitin-specific protease
      14 (Usp14), negatively influences synaptic receptor turnover. Ax(J) mouse
      mutants, characterized by cerebellar ataxia, display both increased GABA(A)
      receptor (GABA(A)R) levels at PC surface membranes accompanied by enlarged IPSCs.
      Accordingly, we identify physical interaction of Usp14 and the GABA(A)R alpha1
      subunit. Although other currently unknown changes might be involved, our data
      show that ubiquitin-dependent GABA(A)R turnover at cerebellar synapses
      contributes to ax(J)-mediated behavioural impairment.

PMID- 19759853
TI  - Synthetic and Computational Studies on the ABC Trioxadispiroketal Subunit of the
      Marine Biotoxin Azaspiracid-1.
AB  - The trioxadispiroketal residue in the marine biotoxin azaspiracid-1, which exists
      in a configuration capable of exhibiting a double anomeric effect, is believed to
      be the thermodynamically most stable bis-spiroketal diastereomer. In order to get
      insight into how structural factors affect this equilibrium, a simplified ABC
      trioxadispiroketal analog of azaspiracid-1 was synthesized and subjected to
      equilbration and computational studies. Compound 7, which represents a double
      anomeric effect was obtained as the major isomer, together with diastereomers 14
      and 15, in a respective ratio of 62:22:16. DFT calculations for 7, 14 and 15
      qualitatively matched this observation. These results suggest that while a double
      anomeric effect may play a major role in the stability of the trioxadispiroketal
      configuration in the more complex natural product, the substitution pattern of
      the C ring is also a contributing factor.

PMID- 19759854
TI  - Control of gel swelling and phase separation of weakly charged thermoreversible
      gels by salt addition.
AB  - Doping of thermoreversible polymer gels with charged monomers provides a way to
      control phase separation and gelation conditions by coupling the properties of
      the gel with a tunable ionic environment. We analyze the dependence of the
      gelation and phase separation conditions on the amount of salt present using a
      mean field model of weakly charged associative polymers. The ions and co-ions
      present are explicitly considered at the mean field level, and we determine their
      concentrations in the different equilibrium phases when the system undergoes
      phase separation. For weak polymer charge, the entropic contributions of the ions
      to the free energy of the system play a central role in the determination of the
      location of phase equilibrium. In the simplest case, when the associative
      interaction responsible for gel formation is independent of the electrostatic
      interaction, the addition of salt changes the polymer equilibrium concentrations
      and indirectly changes the measurable swelling of the gel. We construct phase
      diagrams of these systems showing the location of the coexistence region, the gel
      sol boundary and the location of the tie-lines. We determine the swelling of the
      gel within the co-existence region. Our main result is that the description of
      the effect of the salt on the properties of the weakly charged gel can be
      described through an extra contribution to the effective immiscibility parameter
      chi proportional to the square of the doping degree f(2) and to the inverse
      square of the added salt concentration s(-2).

PMID- 19759855
TI  - Explaining Changes in the Patterns of Black Suicide in the United States From
      1981 to 2002: An Age, Cohort, and Period Analysis.
AB  - To explore the different trends of suicide incidence among Blacks and possible
      contributing factors, the current study compared national epidemiologic data of
      suicide in the United States from 1981 to 2002. For the first time, period and
      birth-cohort effects on the incidence trends of Black suicide were evaluated
      using an age-period-cohort analysis. Cohort effects were found for males and
      females, suggesting that younger generations of Blacks are at higher risk. If
      younger cohorts carry their increased suicide risk into later life, then the
      recent decline in Black suicide rates will be reversed. The results of the
      current study are only interpretable in terms of group-level characteristics and
      population suicide rates and not individual-level characteristics. The possible
      explanation and the implications for prevention and future research are
      discussed.

PMID- 19759856
TI  - Structural Learning of Chain Graphs via Decomposition.
AB  - Chain graphs present a broad class of graphical models for description of
      conditional independence structures, including both Markov networks and Bayesian
      networks as special cases. In this paper, we propose a computationally feasible
      method for the structural learning of chain graphs based on the idea of
      decomposing the learning problem into a set of smaller scale problems on its
      decomposed subgraphs. The decomposition requires conditional independencies but
      does not require the separators to be complete subgraphs. Algorithms for both
      skeleton recovery and complex arrow orientation are presented. Simulations under
      a variety of settings demonstrate the competitive performance of our method,
      especially when the underlying graph is sparse.

PMID- 19759857
TI  - Probing the heme-thiolate oxygenase domain of inducible nitric oxide synthase
      with Ru(II) and Re(I) electron tunneling wires.
AB  - Nitric oxide synthase (NOS) catalyzes the production of nitric oxide from L
      arginine and dioxygen at a thiolate-ligated heme active site. Although many of
      the reaction intermediates are as yet unidentified, it is well established that
      the catalytic cycle begins with substrate binding and rate-limiting electron
      transfer to the heme. Here we show that Ru(II)-diimine and Re(I)-diimine electron
      tunneling wires trigger nanosecond photoreduction of the active-site heme in the
      enzyme. Very rapid generation of a reduced thiolate-ligated heme opens the way
      for direct observation of short-lived intermediates in the NOS reaction cycle.

PMID- 19759858
TI  - Variable increased expression of program death-1 and program death-1 ligands on
      peripheral mononuclear cells is not impaired in patients with systemic lupus
      erythematosus.
AB  - Programmed death-1 (PD-1) was shown to deliver an inhibitory signal after binding
      to its ligands, PD-L1 (B7-H1) or PD-L2 (B7-DC). Recently, up-regulated expression
      of PD-1 molecule and/or its ligands was demonstrated in human diseases including
      rheumatoid arthritis and inflammatory colitis. The study aimed to investigate the
      expression and function of PD-1 and PD-1 ligands on circulating T cells, B cells
      and monocytes from patient with systemic lupus erythematosus (SLE). The results
      showed that patients with SLE had significantly increased percentages of PD-1
      expressing CD3+T cells and CD19+B cells, PD-L1-expressing CD19+B cells and PD-L2
      expressing CD14+B monocytes. In selected SLE patients and normal subjects,
      functional study of PD-1/ PD-1 ligands pathway on the production of cytokines by
      stimulated PBMC was examined. Blockages of PD-1 or PD-1 ligands substantially
      increased the production of IL-2, IFN-gamma and IL-10, the amplitude of increase
      roughly ranged from one to three times. There were no significant differences of
      the enhancing effects on cytokine production by blockage of PD-1/PDL pathway
      between SLE patients and normal subjects. The study indicates that there are no
      intrinsically defective expression and function of PD-1 and PD-1 ligands on PBMC
      in patients with SLE.

PMID- 19759859
TI  - DNA loci cross-talk through thermodynamics.
AB  - The recognition and pairing of specific DNA loci, though crucial for a plenty of
      important cellular processes, are produced by still mysterious physical
      mechanisms. We propose the first quantitative model from Statistical Mechanics,
      able to clarify the interaction allowing such "DNA cross-talk" events. Soluble
      molecules, which bind some DNA recognition sequences, produce an effective
      attraction between distant DNA loci; if their affinity, their concentration, and
      the relative DNA binding sites number exceed given thresholds, DNA colocalization
      occurs as a result of a thermodynamic phase transition. In this paper, after a
      concise report on some of the most recent experimental results, we introduce our
      model and carry out a detailed "in silico" analysis of it, by means of Monte
      Carlo simulations. Our studies, while rationalize several experimental
      observations, result in very interesting and testable predictions.

PMID- 19759860
TI  - DECOMP: a PDB decomposition tool on the web.
AB  - The protein databank (PDB) contains high quality structural data for
      computational structural biology investigations. We have earlier described a fast
      tool (the decomp_pdb tool) for identifying and marking missing atoms and residues
      in PDB files. The tool also automatically decomposes PDB entries into separate
      files describing ligands and polypeptide chains. Here, we describe a web
      interface named DECOMP for the tool. Our program correctly identifies multi
      monomer ligands, and the server also offers the preprocessed ligand-protein
      decomposition of the complete PDB for downloading (up to size: 5GB) AVAILABILITY:
      http://decomp.pitgroup.org.

PMID- 19759861
TI  - D-MATRIX: a web tool for constructing weight matrix of conserved DNA motifs.
AB  - Despite considerable efforts to date, DNA motif prediction in whole genome
      remains a challenge for researchers. Currently the genome wide motif prediction
      tools required either direct pattern sequence (for single motif) or weight matrix
      (for multiple motifs). Although there are known motif pattern databases and tools
      for genome level prediction but no tool for weight matrix construction.
      Considering this, we developed a D-MATRIX tool which predicts the different types
      of weight matrix based on user defined aligned motif sequence set and motif
      width. For retrieval of known motif sequences user can access the commonly used
      databases such as TFD, RegulonDB, DBTBS, Transfac. D-MATRIX program uses a simple
      statistical approach for weight matrix construction, which can be converted into
      different file formats according to user requirement. It provides the possibility
      to identify the conserved motifs in the co-regulated genes or whole genome. As
      example, we successfully constructed the weight matrix of LexA transcription
      factor binding site with the help of known sos-box cis-regulatory elements in
      Deinococcus radiodurans genome. The algorithm is implemented in C-Sharp and
      wrapped in ASP.Net to maintain a user friendly web interface. D-MATRIX tool is
      accessible through the CIMAP domain network. AVAILABILITY:
      http://203.190.147.116/dmatrix/

PMID- 19759862
TI  - PINAT1.0: protein interaction network analysis tool.
AB  - Cellular processes are regulated by interaction of various proteins i.e.
      multiprotein complexes and absences of these interactions are often the cause of
      disorder or disease. Such type of protein interactions are of great interest for
      drug designing. In host-parasite diseases like Tuberculosis, non-homologous
      proteins as drug target are first preference. Most potent drug target can be
      identifying among large number of non-homologous protein through protein
      interaction network analysis. Drug target should be those non-homologous protein
      which is associated with maximum number of functional proteins i.e. has highest
      number of interactants, so that maximum harm can be caused to pathogen only. In
      present work, Protein Interaction Network Analysis Tool (PINAT) has been
      developed to identification of potential protein interaction for drug target
      identification. PINAT is standalone, GUI application software made for protein
      protein interaction (PPI) analysis and network building by using co-evolutionary
      profile. PINAT is very useful for large data PPI study with easiest handling
      among available softwares. PINAT provides excellent facilities for the assembly
      of data for network building with visual presentation of the results and
      interaction score. The software is written in JAVA and provides reliability
      through transparency with user. AVAILABILITY: PINAT is available at
      www.manit.ac.in/pinat.

PMID- 19759863
TI  - CanGeneBase (CGB)--a database on cancer related genes.
AB  - The advent of genomic and proteomic technologies in this post-genomic era has
      urged the researchers to develop novel research strategies against cancer by
      targeting the human genes that would greatly facilitate to identify more
      promising treatment and to develop accurate early diagnosis for cancer. To
      harness the power of cancer genetic information towards better treatment we have
      developed a cancer gene database called CanGeneBase (CGB). It is a comprehensive
      data collection of cancer-related genes with the intention of helping the
      researchers to stay on a single platform to gain exclusive information on the
      genes of their interest. According to the Cancer Gene Data Curation Project,
      about 4,700 genes have been identified as being related to cancer. The present
      CanGeneBase covers about 12 different types of cancer which includes 190 unique
      gene entries. Each entry encompasses about 33 useful parameters to provide
      detailed information about specific gene. CanGeneBase is made in such a way that
      it can be easily accessed by either gene symbol or by the type of cancer.
      AVAILABILITY: The database is freely available at
      http://122.165.25.137/bioinfo/cancerdb/

PMID- 19759864
TI  - Study of codon bias perspective of fungal xylanase gene by multivariate analysis.
AB  - Fungal xylanases has important applications in food, baking, pulp and paper
      industries in addition to various other industries. Xylanases are produced
      extensively by both bacterial and fungal sources and has tremendous potential of
      being active at extremes of temperature and pH. In the present study an effort
      has been made to explore the codon bias perspective of this potential enzyme
      using bioinformatics tools. Multivariate analysis has been used as a tool to
      study codon bias perspectives of xylanases. It was further observed that the
      codon usage of xylanases genes from different fungal sources is not similar and
      to reveal this phenomenon the relative synonymous codon usage (RSCU) and base
      composition variation in fungal xylanase genes were also studied. The codon
      biasing data like GC content at third position (GC(3S)), effective codon number
      (N(C)), codon adaptive index (CAI) were further analyzed with statistical
      softwares like Sigma1plot 9.0 and Systat 11.0. Furthermore, study of translation
      selection was also performed to verify the influences of codon usage variation
      among the 94 xylanase genes. In the present study xylanase gene from 12 organisms
      were analyzed and codon usages of all xylanases from each organism were compared
      separately. Analysis indicates biased codon among all 12 fungi taken for study
      with Aspergillus nidulans, Chaetomium globosum, Aspergillus terreus and
      Aspergillus clavatus showing maximum biasing. N(C) plot and correspondence
      analysis on relative synonymous codon usage indicate that mutation bias and
      translation selection influences codon usage variation in fungal xylanase gene.
      To reveal the relative synonymous codon usage and base composition variation in
      xylanase, 94 genes from 12 fungi were used as model system.

PMID- 19759865
TI  - High temperature unfolding of Bacillus anthracis amidase-03 by molecular dynamics
      simulations.
AB  - The stability of amidase-03 structure (a cell wall hydrolase protein) from
      Bacillus anthracis was studied using classical molecular dynamics (MD)
      simulation. This protein (GenBank accession number: NP_844822) contains an
      amidase-03 domain which is known to exhibit the catalytic activity of N
      acetylmuramoyl-L-alanine amidase (digesting MurNAc-Lalanine linkage of bacterial
      cell wall). The amidase-03 enzyme has stability at high temperature due to the
      core formed by the combination of several secondary structure elements made of
      beta-sheets. We used root-mean-square-displacement (RMSD) of the simulated
      structure from its initial state to demonstrate the unfolding of the enzyme using
      its secondary structural elements. Results show that amidase-03 unfolds in
      transition state ensemble (TSE). The data suggests that alpha-helices unfold
      before beta-sheets from the core during simulation.

PMID- 19759866
TI  - Predicted RNA secondary structures for the conserved regions in dengue virus.
AB  - Dengue fever, dengue hemorrhagic fever and dengue shock syndrome are the
      prevalent mosquito borne viral infections worldwide. The dengue virus belongs to
      the genus flavivirus with conserved RNA domains peptidase_S7 and dexHc among its
      members. The secondary structures for RNA domains peptidase_S7 and DexHc are
      hence predicted and discussed with other known viral RNA structures to glean
      structural insights through comparison.

PMID- 19759867
TI  - Possible role of amyloid-beta, adenine nucleotide translocase and cyclophilin-D
      interaction in mitochondrial dysfunction of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a common neurodegenerative disease characterized by
      both extra- as well as intracellular deposition of amyloid beta peptides (Abeta).
      The accumulation of Abeta in mitochondria is associated with mitochondrial
      dysfunction and oxidative stress in AD. Recent evidences suggest the involvement
      of Abeta interaction with mitochondrial proteins such as cyclophilin-D (CypD) in
      oxidative stress, mitochondrial permeability transition (MPT) and Alzheimer's
      associated neurodegeneration. The present study is an effort to elucidate the
      molecular interaction of Abeta with other proteins involved in MPT like adenine
      nucleotide translocase (ANT). Based on our prediction for sub-cellular
      localization using WolfPSORT and other experimental evidences, we suggest that
      Abeta molecules localize in mitochondrial inner membrane in close vicinity with
      ANT. Our simulation study for protein-protein interaction clearly suggests that
      the ANT-Abeta interaction is stronger than CypD-Abeta interaction. Further the
      lipophilic nature and evidences regarding the localization of Abeta in the
      mitochondrial inner-membrane also support the possibility of strong interaction
      between ANT and Abeta. Interaction between ANT and Abeta may affect normal
      physiological function of ANT i.e. transport of ATP and ADP. Since both the CypD
      Abeta as well as ANT-Abeta interaction are energetically favorable and both CypD
      and ANT are associated with the regulation of MPT, the functional impact of both
      these interactions warrants more in-depth investigations for elucidating the
      mechanisms involved in Abeta-induced oxidative stress.

PMID- 19759868
TI  - Comparative characterization of commercially important xylanase enzymes.
AB  - Xylanase is an industrially important enzyme having wide range of applications
      especially in paper industry. It is crucial to gain an understanding about the
      structure and functional aspects of various xylanases produced from diverse
      sources. In this study, a bioinformatics and molecular modeling approach was
      adopted to explore properties and structure of xylanases. Physico-chemical
      properties were predicted and prediction of motifs, disulfide bridges and
      secondary structure was performed for functional characterization. Apart from
      these analyses, three dimensional structures were constructed and stereo-chemical
      quality was evaluated by different structure validation tools. Comparative
      catalytic site analysis and assessment was performed to extract information about
      the important residues. Asn72 was found to be the common residue in the active
      sites of the proteins P35809 and Q12603.

PMID- 19759869
TI  - Prediction of nucleosome positions in the yeast genome based on matched mirror
      position filtering.
AB  - Nucleosome positioning can affect the accessibility of the underlying DNA to the
      nuclear environment and as such plays an essential role in the regulation of
      cellular processes. Specific patterns have been found in the underlying DNA
      sequences of the nucleosome, and one of the most important patterns includes
      dinucleotides distributed every 10 to 11 base pairs. Based on this property, we
      propose to match each dinucleotide in the sequence against its mirror occurrences
      for 10 to 11 base pairs on both left-hand and right-hand sides. A large number of
      matches in a local region will then signify the existence of a nucleosome. In
      this paper, we propose the matched mirror position filters for efficient matching
      of periodic dinucleotide patterns and computationally predict the nucleosome
      positions. Experimental results on the Saccharomyces cerevisiae (yeast) genome
      show that the proposed algorithm can predict nucleosome positions effectively.
      More than 50% of our predicted nucleosomes are within 35 base pairs of those
      detected by biological experiments.

PMID- 19759870
TI  - Pathology, pathogenesis and therapy of growth hormone (GH)-producing pituitary
      adenomas: technical advances in histochemistry and their contribution.
AB  - Growth hormone (GH)-producing adenomas (GHomas) are one of the most frequently
      occurring pituitary adenomas. Differentiation of hormone-producing cells in the
      pituitary gland is regulated by transcription factors and co-factors. The
      transcription factors include Pit-1, Prop-1, NeuroD1, Tpit, GATA-2, SF-1.
      Aberrant expression of transcription factors such as Pit-1 results in
      translineage expression of GH in adrenocorticotropic hormone-producing adenomas
      (ACTHomas). This situation has been substantiated by GFP-Pit-1 transfection
      expression in the AtT20 cell line. Experimentally, GHomas have been induced in GH
      releasing hormone (GHRH) or Prop-1 transgenic animals. Immunohistochemical
      detection of somatostatin receptor (SSTR2a) has recently emphasized their role in
      the response of GHomas to somatostatin analogue therapy. In this review, the
      advances in technology and their contribution to cell biology and medical
      practice are discussed.

PMID- 19759871
TI  - Immunohistochemical demonstration of membrane-bound prostaglandin E2 synthase-1
      in papillary thyroid carcinoma.
AB  - Microsomal prostaglandin E(2) synthase-1 (mPGES-1) is an inducible enzyme that
      catalyzes the conversion of prostaglandin (PG) H(2) to PGE(2) in downstream of
      cyclooxygenase-2 (COX-2). Recent studies have obtained in vitro evidence that
      PGE(2) participates in carcinogenesis, angiogenesis, and induction of matrix
      metalloproteinase-9 (MMP-9), which plays a crucial role in cancer invasion.
      However, implications for mPGES-1 in thyroid carcinomas remain to be determined.
      To address this issue, we performed an immunohistochemical analysis for mPGES-1,
      COX-2 and MMP-9 in 20 papillary thyroid carcinoma (PTC) patients. mPGES-1
      immunoreactivity was localized in the cytoplasm of carcinoma cells in 19 cases,
      with an intensity that tended to be distinct at the interface between the tumor
      and the surrounding non-neoplastic tissue. Staining was more intense in regions
      with papillary arrangement, while it was less intense in regions with trabecular
      or solid arrangement. In many cases, immunohistochemical localization of COX-2
      and MMP-9 resemble that of mPGES-1. Taken together, our results suggest the
      involvement of mPGES-1 in proliferation and differentiation of PTC as well as
      local invasion of PTC.

PMID- 19759872
TI  - Neurokinin-1 receptor immunoreactive neuronal elements in the superficial dorsal
      horn of the chicken spinal cord: with special reference to their relationship
      with the tachykinin-containing central axon terminals in synaptic glomeruli.
AB  - Synaptic glomeruli that involve tachykinin-containing primary afferent central
      terminals are numerous in lamina II of the chicken spinal cord. Therefore, a
      certain amount of noxious information is likely to be modulated in these
      structures in chickens. In this study, we used immunohistochemistry with confocal
      and electron microscopy to investigate whether neurokinin-1 receptor (NK-1R)
      expressing neuronal elements are in contact with the central primary afferent
      terminals in synaptic glomeruli of the chicken spinal cord. We also investigated
      which neuronal elements (axon terminals, dendrites, cell bodies) and which
      neurons in the spinal cord possess NK-1R, and are possibly influenced by
      tachykinin in the glomeruli. By confocal microscopy, NK-1R immunoreactivities
      were seen in a variety of neuronal cell bodies, their dendrites and smaller
      fibers of unknown origin. Some of the NK-1R immunoreactive profiles also
      expressed GABA immunoreactivities. A close association was observed between the
      NK-1R-immunoreactive neurons and tachykinin-immunoreactive axonal varicosities.
      By electron microscopy, NK-1R immunoreactivity was seen in cell bodies,
      conventional dendrites and vesicle-containing dendrites in laminae I and II.
      Among these elements, dendrites and vesicle-containing dendrites made contact
      with tachykinin-containing central terminals in the synaptic glomeruli. These
      results indicate that tachykinin-containing central terminals in the chicken
      spinal cord can modulate second-order neuronal elements in the synaptic
      glomeruli.

PMID- 19759873
TI  - The effects of diuretics on intracellular Ca2+ dynamics of arteriole smooth
      muscles as revealed by laser confocal microscopy.
AB  - The regulation of cytosolic Ca(2+) homeostasis is essential for cells, including
      vascular smooth muscle cells. Arterial tone, which underlies the maintenance of
      peripheral resistance in the circulation, is a major contributor to the control
      of blood pressure. Diuretics may regulate intracellular Ca(2+) concentration
      ([Ca(2+)](i)) and have an effect on vascular tone. In order to investigate the
      influence of diuretics on peripheral resistance in circulation, we investigated
      the alteration of [Ca(2+)](i) in testicular arterioles with respect to several
      categories of diuretics using real-time confocal laser scanning microscopy. In
      this study, hydrochlorothiazide (100 microM) and furosemide (100 microM) had no
      effect on the [Ca(2+)](i) dynamics. However, when spironolactone (300 microM) was
      applied, the [Ca(2+)](i) of smooth muscles increased. The response was
      considerably inhibited under either extracellular Ca(2+)-free conditions, the
      presence of Gd(3+), or with a treatment of diltiazem. After the thapsigargin
      induced depletion of internal Ca(2+) store, the spironolactone-induced
      [Ca(2+)](i) dynamics was slightly inhibited. Therefore, the spironolactone
      induced dynamics of [Ca(2+)](i) can be caused by either a Ca(2+) influx from
      extracellular fluid or Ca(2+) mobilization from internal Ca(2+) store, with the
      former being dominant. As tetraethylammonium, an inhibitor of the K(+) channel,
      slightly inhibited the spironolactone-induced [Ca(2+)](i) dynamics, the K(+)
      channel might play a minor role in those dynamics. Tetrodotoxin, a neurotoxic
      Na(+) channel blocker, had no effect, therefore the spironolactone-induced
      dynamics is a direct effect to smooth muscles, rather than an indirect effect via
      vessel nerves.

PMID- 19759875
TI  - Reasons for resubmission of research projects to the research ethics committee of
      a university hospital in Sao Paulo, Brazil.
AB  - INTRODUCTION: It is important to know the reasons for resubmitting research
      projects to the Research Ethics Committee in order to help researchers to prepare
      their research projects, informed consent forms and needed research
      documentation. OBJECTIVES: To verify the reasons for resubmitting projects that
      were previously rejected by the Ethics Committee. METHOD: This is a cross
      sectional study that evaluated research projects involving human beings. Research
      projects were submitted in 2007 to the Research Ethics Committee of the Hospital
      das Clinicas, Faculdade de Medicina da Universidade de Sao Paulo. RESULTS: One
      thousand two hundred and fifty six research projects were submitted to the ethics
      committee and the average time for evaluating the research projects and related
      documents until a final decision was reached was 49.95 days. From the total, 399
      projects were reviewed in 2 or more meetings until a final decision was reached.
      Of these, 392 research projects were included in the study; 35 projects were
      subsequently excluded for involving animals. Among the research projects
      included, 42.5% concerned research with new drugs, vaccines and diagnostic tests,
      48.5% consisted of undergraduate students' research projects, 68.9% of the
      research had no sponsorship, and 97.5% were eventually approved. The main reasons
      for returning the projects to the researchers were the use of inadequate language
      and/or difficulty of understanding the informed consent form (32.2%), lack of
      information about the protocol at the informed consent form (25.8%), as well as
      doubts regarding methodological and statistical issues of the protocol (77.1%).
      Other reasons for returning the research projects involved lack of, inaccuracy on
      or incomplete documentation, need of clarification or approval for participation
      of external entities on the research, lack of information on financial support.
      CONCLUSION: Among the research projects that were returned to the researchers for
      additional clarification, the main reasons were inadequacies or doubts about the
      terms used in the informed consent form as well as lack of information regarding
      the research at the informed consent form and methodological and statistical
      issues regarding the protocol.

PMID- 19759876
TI  - Analysis of HFE and non-HFE gene mutations in Brazilian patients with
      hemochromatosis.
AB  - BACKGROUND: Approximately one-half of Brazilian patients with hereditary
      hemochromatosis (HH) are neither homozygous for the C282Y mutation nor compound
      heterozygous for the H63D and C282Y mutations that are associated with HH in
      Caucasians. Other mutations have been described in the HFE gene as well as in
      genes involved in iron metabolism, such as transferrin receptor 2 (TfR2) and
      ferroportin 1 (SCL40A1). AIMS: To evaluate the role of HFE, TfR2 and SCL40A1
      mutations in Brazilian subjects with HH. PATIENTS AND METHODS: Nineteen male
      subjects (median age 42 [range: 20-72] years) with HH were evaluated using the
      Haemochromatosis StripAssay A. This assay is capable of detecting twelve HFE
      mutations, which are V53M, V59M, H63D, H63H, S65C, Q127H, P160delC, E168Q, E168X,
      W169X, C282Y and Q283, four TfR2 mutations, which are E60X, M172K, Y250X, AVAQ594
      597del, and two SCL40A1 mutations, which are N144H and V162del. RESULTS: In our
      cohort, nine (47%) patients were homozygous for the C282Y mutation, two (11%)
      were heterozygous for the H63D mutation, and one each (5%) was either
      heterozygous for C282Y or compound heterozygous for C282Y and H63D. No other
      mutations in the HFE, TfR2 or SCL40A1 genes were observed in the studied
      patients. CONCLUSIONS: One-third of Brazilian subjects with the classical
      phenotype of HH do not carry HFE or other mutations that are currently associated
      with the disease in Caucasians. This observation suggests a role for other yet
      unknown mutations in the aforementioned genes or in other genes involved in iron
      homeostasis in the pathogenesis of HH in Brazil.

PMID- 19759877
TI  - Oral maxillofacial fractures seen at a Ugandan tertiary hospital: a six-month
      prospective study.
AB  - AIM: To investigate the epidemiological characteristics of maxillofacial
      fractures and associated fractures in patients seen in the Oral Surgery Unit of
      Mulago Hospital, Kampala, Uganda. METHODOLOGY: A six-month prospective study was
      conducted. Data collected included socio-demographic factors, type and etiology
      of injury, additional fractures, and post-surgery complications. RESULTS: One
      hundred thirty-two (132) cases ranging from 5-70 yrs of age were reported, with a
      male: female ratio of 7.7:1. The 21-30 yr age group was the largest, comprising
      51.51% of cases (n=68). Road traffic accidents contributed to 56.06% (n=74) of
      fractures. In total, 66% of the sample (n=87) suffered isolated mandibular
      fractures. Symphyseal and maxillary fractures were the most common mandibular and
      mid-facial fractures, respectively. Among associated fractures, the femur was
      most affected. A total of 39 (29.54%) of patients had post-operative
      complications, of which infection accounted for 48.71% (n=19), and malocclusion
      accounted for 17.94% (n=7). CONCLUSIONS: Anticipated changes in maxillofacial
      trauma trends necessitate regular epidemiologic studies of facial fractures to
      allow for development and implementation of timely novel preventive measures.

PMID- 19759878
TI  - Prognostic influence of clinical and pathological factors in medullary thyroid
      carcinoma: a study of 53 cases.
AB  - OBJECTIVES AND INTRODUCTION: Medullary thyroid carcinoma, a neoplasia of
      intermediate prognosis and differentiation, does not always respond predictably
      to known treatments. This study aimed to correlate the clinical progression of
      surgically treated patients with clinical and pathological data. METHODS: A total
      of 53 patients were followed for 75 months (mean average) in tertiary-care
      hospital. The clinical status of patients at the end of the study period was
      characterized to determine correlations with a range of disease aspects. A value
      of p < 0.05 was considered statistically significant. RESULTS: Twenty-two
      patients (41.5%) were alive and disease-free at the end of the follow-up period;
      twenty-three patients (43.4%) had persistent disease; and eight patients (15.1%)
      had recurrent disease. Four patients (7.6%) died from medullary thyroid carcinoma
      with clinical and/or imaging evidence of neoplasia. The following aspects
      demonstrated statistically significant correlations with the final medical
      condition: positive initial cervical examination (p = 0.002); neoplastic
      extensions to the thyroid capsule (p = 0.004) and adjacent tissues (p = 0.034);
      cervical lymph node metastases (p < 0.001); diameter of neoplasia (p = 0.018);
      TNM (tumor, node and metastasis) Stage (p = 0.001) and evidence of distant and/or
      cervical diseases in the absence of a cure (p = 0.011). Through logistic
      regression, the presence of cervical lymph node metastases was considered an
      independent variable (p < 0.001). CONCLUSIONS: Clinical and pathological aspects
      of patients with surgically treated medullary thyroid carcinomas are predictors
      of disease progression. Specifically, even treated cervical lymph node metastases
      are significantly correlated with disease progression.

PMID- 19759879
TI  - Crack cocaine use and its relationship with violence and HIV.
AB  - OBJECTIVES: To evaluate crack cocaine use practices, risk behaviors associated
      with HIV infection among drug users, and their involvement with violence.
      INTRODUCTION: HIV infections are frequent among drug users due to risky sexual
      behavior. It is generally accepted that crack cocaine use is related to increased
      levels of violence. Several reports point to an increase in violence from those
      involved in drug trafficking. Although HIV infections and risky sexual behavior
      among drug users have been quite well studied, there are few studies that
      evaluate violence as it relates to drugs, particularly crack. METHODS: A total of
      350 drug users attending drug abuse treatment clinics in Sao Paulo, Brazil were
      interviewed about their risky behaviors. Each patient had a serological HIV test
      done. RESULTS: HIV prevalence was 6.6% (4.0 to 10.2). Violence was reported by
      97% (94.7 to 99.1) of the subjects (including cases without personal
      involvement). Acts of violence such as verbal arguments, physical fights,
      threats, death threats, theft, and drug trafficking were significantly higher
      among crack users. A decrease in frequency of sexual intercourse was observed
      among users of injected drugs, though prostitution was observed as a means of
      obtaining drugs. A high number of crack cocaine users had a history of previous
      imprisonment, many for drug-related infractions. DISCUSSION: The data presented
      are in accordance with other reports in the literature, and they show a
      correlation between drug use, imprisonment, violence, and drug trafficking.
      CONCLUSION: A high HIV prevalence and associated risky sexual behaviors were
      observed among crack cocaine users. The society and the authorities that deal
      with violence related to crack users and drug trafficking should be aware of
      these problems.

PMID- 19759880
TI  - Quality of life among HIV-infected patients in Brazil after initiation of
      treatment.
AB  - INTRODUCTION: Despite improvement in clinical treatment for HIV-infected
      patients, the impact of antiretroviral therapy on the overall quality of life has
      become a major concern. OBJECTIVE: To identify factors associated with increased
      levels of self-reported quality of life among HIV-infected patients after four
      months of antiretroviral therapy. METHODS: Patients were recruited at two public
      health referral centers for AIDS, Belo Horizonte, Brazil, for a prospective
      adherence study. Patients were interviewed before initiating treatment (baseline)
      and after one and four months. Quality of life was assessed using a psychometric
      instrument, and factors associated with good/very good quality of life four
      months after the initiation of antiretroviral therapy were assessed using a cross
      sectional approach. Logistic regression was used for analysis. RESULTS: Overall
      quality of life was classified as 'very good/good' by 66.4% of the participants
      four months after initiating treatment, while 33.6% classified it as 'neither
      poor nor good/poor/very poor'. Logistic regression indicated that >8 years of
      education, none/mild symptoms of anxiety and depression, no antiretroviral
      switch, lower number of adverse reactions and better quality of life at baseline
      were independently associated with good/very good quality of life over four
      months of treatment. CONCLUSIONS: Our results highlight the importance of
      modifiable factors such as psychiatric symptoms and treatment-related variables
      that may contribute to a better quality of life among patients initiating
      treatment. Considering that poor quality of life is related to non-adherence to
      antiretroviral therapy, careful clinical monitoring of these factors may
      contribute to ensuring the long-term effectiveness of antiretroviral regimens.

PMID- 19759881
TI  - Quality of life in the late follow-up of ulcerative colitis patients submitted to
      restorative proctocolectomy with sphincter preservation over ten years ago.
AB  - OBJECTIVE: To evaluate, by means of the Inflammatory Bowel Disease Questionnaire
      (IBDQ), the quality of life of ulcerative colitis patients submitted to
      proctocolectomy with sphincter preservation using J-pouch reconstruction over ten
      years ago. METHODS: The study consisted of 36 patients interviewed using the
      Inflammatory Bowel Disease Questionnaire. The score scale, resulting from the
      addition of each answer, ranged from 32 to 224, where the highest score indicates
      the best quality of life. The chi square test was used to verify the existence of
      meaningful differences between the results of the questionnaire and age, and
      gender proportion. For each section, as well as for all of them combined, the
      Kruskal-Wallis test was used to verify if there were differences in the
      Inflammatory Bowel Disease Questionnaire scores among the groups in relation to
      the proportions. RESULTS: After applying the Inflammatory Bowel Disease
      Questionnaire, it was determined that quality of life was considered excellent
      for 9 (25%), good for 11 (30.6%), regular for 13 (36.1%), and bad for 3 (8.3%)
      patients. In our study, we determined that 85% of the patients were pleased with
      and thankful for the surgery that they underwent. CONCLUSION: We can conclude
      that the possibility of sphincter preservation should always be taken into
      account, since patients remain clinically stable and have a high quality of life
      even after long periods.

PMID- 19759882
TI  - Comparative evaluation of oculometric variables in Graves' ophthalmopathy.
AB  - OBJECTIVES: To estimate oculometric parameters of Graves' ophthalmopathy in
      comparison to healthy eyes using digital photography and digital image analysis.
      INTRODUCTION: Graves' ophthalmopathy is the main cause of eye proptosis. Because
      these protrusions cause clinically perceived distortions in orbital architecture,
      digital photographs can be used to detect and quantify these changes. METHODS: We
      carried out a cross-sectional study comprising 12 healthy volunteers and 15
      Graves' ophthalmopathy patients with the purpose of evaluating the use of simple,
      non-invasive digital photography to estimate oculometric parameters of Graves'
      ophthalmopathy and compare them with the parameters of unaffected eyes. Facial
      photographs of cases and controls were taken in a standardized manner.
      Oculometric parameters were compared between the groups and then correlated to
      proptometer measures. RESULTS: All estimated oculometric variables showed
      significant differences between the groups, in particular with regard to
      mediopupilar aperture, lateral height, distance from the iris edge to the lateral
      boundary of the palpebral fissure, and distance from the higher point of the iris
      to the lateral limit of the palpebral fissure. The product of medial aperture and
      horizontal palpebral fissure also revealed greater discrepancy between the
      groups. Proptometer measures showed significant linear correlation between the
      distance from the iris edge to the lateral boundary of the palpebral fissure and
      between the distance from the higher point of the iris to the lateral limit of
      palpebral fissure (p<0.05). CONCLUSIONS: Comparative analysis of oculometric
      parameters in Graves' ophthalmopathy suggests that eye proptosis is related to an
      asymmetric increase in lateral oculometric measures. Standardized digital
      photographs can be used in clinical practice to objectively estimate oculometric
      parameters of Graves' ophthalmopathy patients.

PMID- 19759883
TI  - Does the evaluation of coagulation factors contribute to etiological diagnosis of
      pleural effusions?
AB  - OBJECTIVE: The aim of this study was to identify the participation of the
      coagulation system in the differential diagnosis of pleural effusions.
      INTRODUCTION: Imbalance between immunologic and metabolic factors triggers a
      sequence of events resulting in pleural reactions and accumulation of fluid. The
      coagulation system, which is fundamental for the maintenance of homeostasis,
      contributes to the inflammatory process responsible for pleural effusions, and
      participates in cellular proliferation and migration as well as in the synthesis
      of inflammatory mediators. METHODS: We evaluated the laboratory profile of
      coagulation and fibrinolysis in 54 pleural fluids (15 transudates and 39
      exudates). RESULTS: The coagulation system acts according to the pathophysiologic
      mechanisms involved in the development of pleural effusions. In inflammatory
      effusions (exudates), there is activation of coagulation with increased levels of
      fragment 1+2 and thrombin-antithrombin complex in addition to reduction of
      fibrinogen levels due to fibrinolysis and fibrin tissue incorporation. As a
      consequence, there is activation of the fibrinolytic system with increased levels
      of fibrin degradation products, including the D-dimer. These changes are not
      sufficient for differentiation of different subgroups of exudates. In
      transudates, these events were observed to a lesser degree. CONCLUSION: The
      coagulation system plays an important role in the development of pleural
      diseases. Coagulation tests show differences between transudates and exudates but
      not among exudate subgroups. Understanding the physiopathological mechanisms of
      pleural disorders may help to define new diagnostic and therapeutic approaches.

PMID- 19759884
TI  - Variability in the origin of the obturator artery.
AB  - INTRODUCTION: General surgeons dealing with laparoscopic herniorrhaphy should be
      aware of the aberrant obturator artery that crosses the superior pubic ramus and
      is susceptible to injuries during dissection of the Bogros space and mesh
      stapling onto Cooper's ligament. The obturator artery is usually described as a
      branch of the anterior division of the internal iliac artery, although variations
      have been reported. MATERIALS AND METHODS: The present study was conducted on 98
      pelvic halves of embalmed cadavers, and the origin and course of the obturator
      artery were traced and noted. RESULTS: In 79% of the specimens, the obturator
      artery was a branch of the internal iliac artery. It branched off at different
      levels either from the anterior division or posterior division, individually or
      with other named branches. In 19% of the cases, the obturator artery branched off
      from the external iliac artery as a separate branch or with the inferior
      epigastric artery. However, in the remaining 2% of the specimens, both the
      internal and the external iliac arteries branched to form an anastomotic
      structure within the pelvic cavity. CONCLUSION: The data obtained in this study
      show that it is more common to find an abnormal obturator artery than was
      reported previously, and this observation has implications for pelvic surgeons
      and is of academic interest to anatomists. Surgeons dealing with direct,
      indirect, femoral, or obturator hernias need to be aware of these variations and
      their close proximity to the femoral ring.

PMID- 19759885
TI  - The scientific production of full professors of the Faculdade de Medicina da
      Universidade de Sao Paulo: a view of the period of 2001-2006.
AB  - INTRODUCTION: The scientific production of institutions of higher education, as
      well as the dissemination and use of this published work by peer institutions,
      can be assessed by means of quantitative and qualitative measurements. This type
      of analysis can also serve as the basis of further academic actions. Variables
      such as the type of evaluation, the number of faculty members and the decision to
      include or exclude researchers who are not professors are difficult to measure
      when comparing different schools and institutions. OBJECTIVES: The purpose of
      this study was to assess the scientific production of tenured faculty from the
      Universidade de Sao Paulo, Faculdade de Medicina performed from 2001 to 2006.
      METHODS: Medline/PubMed database was considered and the Impact factors (IFs-
      Journal Citation Report, 2006) and the number of generated citations (Web of
      Science/ISI Thomson) were also evaluated. RESULTS: The analysis of the scientific
      production of 66 full professors (level MS-6) revealed 1,960 scientific articles
      published in 630 scientific journals, of which 31.3% were Brazilian and 68.7%
      were from international sources. Among these, 47% of the articles were published
      in 62.9% of the journals with IFs above 10, although 16.4% of the journals did
      not have assigned IF values. We verified that 45% of the published articles
      received 9,335 citations (average of 11 + 17), with the majority of these (8,968
      citations) appearing in international scientific journals. CONCLUSIONS: Our
      results indicate that it is possible to analyze the scientific production of a
      learning institution by the number of papers published by full professors, taking
      into account not only their academic position and influence, but also the fact
      that publication is an opportunity to stimulate joint projects with other members
      of the same institution.

PMID- 19759886
TI  - Mesenteric microcirculatory dysfunctions and translocation of indigenous bacteria
      in a rat model of strangulated small bowel obstruction.
AB  - PURPOSE: Bacterial translocation has been shown to occur in critically ill
      patients after extensive trauma, shock, sepsis, or thermal injury. The present
      study investigates mesenteric microcirculatory dysfunctions, the bacterial
      translocation phenomenon, and hemodynamic/metabolic disturbances in a rat model
      of intestinal obstruction and ischemia. METHODS: Anesthetized (pentobarbital 50
      mg/kg, i.p.) male Wistar rats (250-350 g) were submitted to intestinal
      obstruction or laparotomy without intestinal obstruction (Sham) and were
      evaluated 24 hours later. Bacterial translocation was assessed by bacterial
      culture of the mesenteric lymph nodes (MLN), liver, spleen, and blood. Leukocyte
      endothelial interactions in the mesenteric microcirculation were assessed by
      intravital microscopy, and P-selectin and intercellular adhesion molecule (ICAM)
      1 expressions were quantified by immunohistochemistry. Hematocrit, blood gases,
      lactate, glucose, white blood cells, serum urea, creatinine, bilirubin, and
      hepatic enzymes were measured. RESULTS: About 86% of intestinal obstruction rats
      presented positive cultures for E. coli in samples of the mesenteric lymph nodes,
      liver, and spleen, and 57% had positive hemocultures. In comparison to the Sham
      rats, intestinal obstruction induced neutrophilia and increased the number of
      rolling (approximately 2-fold), adherent (approximately 5-fold), and migrated
      leukocytes (approximately 11-fold); this increase was accompanied by an increased
      expression of P-selectin (approximately 2-fold) and intercellular adhesion
      molecule-1 (approximately 2-fold) in the mesenteric microcirculation. Intestinal
      obstruction rats exhibited decreased PaCO2, alkalosis, hyperlactatemia, and
      hyperglycemia, and increased blood potassium, hepatic enzyme activity, serum
      urea, creatinine, and bilirubin. A high mortality rate was observed after
      intestinal obstruction (83% at 72 h vs. 0% in Sham rats). CONCLUSION: Intestinal
      obstruction and ischemia in rats is a relevant model for the in vivo study of
      mesenteric microcirculatory dysfunction and the occurrence of bacterial
      translocation. This model parallels the events implicated in multiple organ
      dysfunction (MOD) and death.

PMID- 19759887
TI  - Memantine prevents cardiomyocytes nuclear size reduction in the left ventricle of
      rats exposed to cold stress.
AB  - OBJECTIVES: Memantine is an N-methyl-d-aspartate (NMDA) glutamate receptor
      antagonist used to treat Alzheimer's disease. Previous studies have suggested
      that receptor blockers act as neuroprotective agents; however, no study has
      specifically investigated the impact that these drugs have on the heart. We
      sought to evaluate the effects of memantine on nuclear size reduction in cardiac
      cells exposed to cold stress. METHOD: We used male EPM-Wistar rats (n=40) divided
      into 4 groups: 1) Matched control (CON); 2) Memantine-treated rats (MEM); 3) Rats
      undergoing induced hypothermia (IH) and 4) Rats undergoing induced hypothermia
      that were also treated with memantine (IHM). Animals in the MEM and IHM groups
      were treated by oral gavage administration of 20 mg/kg/day memantine over an
      eight-day period. Animals in the IH and IHM groups were submitted to 4 hours of
      hypothermia in a controlled environment with a temperature of -8 degrees C on the
      last day of the study. RESULTS: The MEM group had the largest cardiomyocyte
      nuclear size (151 +/- 3.5 microm(3) vs. CON: 142 +/- 2.3 microm(3); p<0.05),
      while the IH group had the smallest mean value of nuclear size. The nuclear size
      of the IHM group was preserved (125 +/- 2.9 microm(3)) compared to the IH group
      (108 +/- 1.7 microm(3); p<0.05). CONCLUSION: Memantine prevented the nuclear size
      reduction of cardiomyocytes in rats exposed to cold stress.

PMID- 19759888
TI  - Acute chest syndrome in pregnant women with hemoglobin SC disease.

PMID- 19759889
TI  - Classic abdominoplasty: a new approach to the correction of the abdominal wall
      deformity in patients with bladder exstrophy--a case report.

PMID- 19759890
TI  - Unusual combination of reversible splenial lesion and meningitis-retention
      syndrome in aseptic meningomyelitis.

PMID- 19759891
TI  - VON MISES-FISHER MIXTURE MODEL OF THE DIFFUSION ODF.
AB  - High angular resolution diffusion imaging (HARDI) permits the computation of
      water molecule displacement probabilities over the sphere. This probability is
      often referred to as the orientation distribution function (ODF). In this paper
      we present a novel model for representing this diffusion ODF namely, a mixture of
      von Mises-Fisher (vMF) distributions. Our model is compact in that it requires
      very few parameters to represent complicated ODF geometries which occur
      specifically in the presence of heterogeneous nerve fiber orientations. We
      present a Riemannian geometric framework for computing intrinsic distances (in
      closed-form) and for performing interpolation between ODFs represented by vMF
      mixtures. We also present closed-form equations for entropy and variance based
      anisotropy measures that are then computed and illustrated for real HARDI data
      from a rat brain.

PMID- 19759892
TI  - A novel liposome-based adjuvant CAF01 for induction of CD8(+) cytotoxic T
      lymphocytes (CTL) to HIV-1 minimal CTL peptides in HLA-A*0201 transgenic mice.
AB  - BACKGROUND: Specific cellular cytotoxic immune responses (CTL) are important in
      combating viral diseases and a highly desirable feature in the development of
      targeted HIV vaccines. Adjuvants are key components in vaccines and may assist
      the HIV immunogens in inducing the desired CTL responses. In search for
      appropriate adjuvants for CD8(+) T cells it is important to measure the necessary
      immunological features e.g. functional cell killing/lysis in addition to
      immunological markers that can be monitored by simple immunological laboratory
      methods. METHODOLOGY/PRINCIPAL FINDINGS: We tested the ability of a novel two
      component adjuvant, CAF01, consisting of the immune stimulating synthetic
      glycolipid TDB (Trehalose-Dibehenate) incorporated into cationic DDA
      (Dimethyldioctadecylammonium bromide) liposomes to induce CD8(+) T-cell
      restricted cellular immune responses towards subdominant minimal HLA-A0201
      restricted CTL epitopes from HIV-1 proteins in HLA-A*0201 transgenic HHD mice.
      CAF01 has an acceptable safety profile and is used in preclinical development of
      vaccines against HIV-1, malaria and tuberculosis. CONCLUSIONS/SIGNIFICANCE: We
      found that CAF01 induced cellular immune responses against HIV-1 minimal CTL
      epitopes in HLA-A*0201 transgenic mice to levels comparable with that of
      incomplete Freund's adjuvant.

PMID- 19759893
TI  - Crosstalk between spinal astrocytes and neurons in nerve injury-induced
      neuropathic pain.
AB  - Emerging research implicates the participation of spinal dorsal horn (SDH)
      neurons and astrocytes in nerve injury-induced neuropathic pain. However, the
      crosstalk between spinal astrocytes and neurons in neuropathic pain is not clear.
      Using a lumbar 5 (L5) spinal nerve ligation (SNL) pain model, we testified our
      hypothesis that SDH neurons and astrocytes reciprocally regulate each other to
      maintain the persistent neuropathic pain states. Glial fibrillary acidic protein
      (GFAP) was used as the astrocytic specific marker and Fos, protein of the
      protooncogene c-fos, was used as a marker for activated neurons. SNL induced a
      significant mechanical allodynia as well as activated SDH neurons indicated by
      the Fos expression at the early phase and activated astrocytes with the increased
      expression of GFAP during the late phase of pain, respectively. Intrathecal
      administration of c-fos antisense oligodeoxynucleotides (ASO) or astroglial toxin
      L-alpha-aminoadipate (L-AA) reversed the mechanical allodynia, respectively.
      Immunofluorescent histochemistry revealed that intrathecal administration of c
      fos ASO significantly suppressed activation of not only neurons but also
      astrocytes induced by SNL. Meanwhile, L-AA shortened the duration of neuronal
      activation by SNL. Our data offers evidence that neuronal and astrocytic
      activations are closely related with the maintenance of neuropathic pain through
      a reciprocal "crosstalk". The current study suggests that neuronal and non
      neuronal elements should be taken integrally into consideration for nociceptive
      transmission, and that the intervention of such interaction may offer some novel
      pain therapeutic strategies.

PMID- 19759894
TI  - Does the order of invasive species removal matter? The case of the eagle and the
      pig.
AB  - BACKGROUND: Invasive species are recognized as a primary driver of native species
      endangerment and their removal is often a key component of a conservation
      strategy. Removing invasive species is not always a straightforward task,
      however, especially when they interact with other species in complex ways to
      negatively influence native species. Because unintended consequences may arise if
      all invasive species cannot be removed simultaneously, the order of their removal
      is of paramount importance to ecological restoration. In the mid-1990s, three
      subspecies of the island fox Urocyon littoralis were driven to near extinction on
      the northern California Channel Islands owing to heightened predation by golden
      eagles Aquila chrysaetos. Eagles were lured to the islands by an abundant supply
      of feral pigs Sus scrofa and through the process of apparent competition pigs
      indirectly facilitated the decline in foxes. As a consequence, both pigs and
      eagles had to be removed to recover the critically endangered fox. Complete
      removal of pigs was problematic: removing pigs first could force eagles to
      concentrate on the remaining foxes, increasing their probability of extinction.
      Removing eagles first was difficult: eagles are not easily captured and lethal
      removal was politically distasteful. METHODOLOGY/PRINCIPAL FINDINGS: Using prey
      remains collected from eagle nests both before and after the eradication of pigs,
      we show that one pair of eagles that eluded capture did indeed focus more on
      foxes. These results support the premise that if the threat of eagle predation
      had not been mitigated prior to pig removal, fox extinction would have been a
      more likely outcome. CONCLUSIONS/SIGNIFICANCE: If complete eradication of all
      interacting invasive species is not possible, the order in which they are removed
      requires careful consideration. If overlooked, unexpected consequences may result
      that could impede restoration.

PMID- 19759895
TI  - Paternal mtDNA and maleness are co-inherited but not causally linked in mytilid
      mussels.
AB  - BACKGROUND: In marine mussels of the genus Mytilus there are two mitochondrial
      genomes. One is transmitted through the female parent, which is the normal
      transmission route in animals, and the other is transmitted through the male
      parent which is an unusual phenomenon. In males the germ cell line is dominated
      by the paternal mitochondrial genome and the somatic cell line by the maternal.
      Research to date has not allowed a clear answer to the question of whether
      inheritance of the paternal genome is causally related to maleness.
      METHODOLOGY/PRINCIPAL FINDINGS: Here we present results from hybrid crosses, from
      triploid mussels and from observations of sperm mitochondria in fertilized eggs
      which clearly show that maleness and presence of the paternal mitochondrial
      genome can be decoupled. These same results show that the female mussel has
      exclusive control of whether her progeny will inherit the mitochondrial genome of
      the male parent. CONCLUSIONS/SIGNIFICANCE: These findings are important in our
      efforts to understand the mechanistic basis of this unusual mode of mitochondrial
      DNA inheritance that is common among bivalves.

PMID- 19759896
TI  - Effects of endotoxaemia on protein metabolism in rat fast-twitch skeletal muscle
      and myocardium.
AB  - BACKGROUND: It is unclear if the rat myocardium undergoes the same rapid
      reductions in protein content that are classically observed in fast-twitch
      skeletal muscle during endotoxaemia. METHODOLOGY/PRINCIPAL FINDINGS: To
      investigate this further, and to determine if there is any divergence in the
      response of skeletal muscle and myocardium in the mechanisms that are thought to
      be largely responsible for eliciting changes in protein content, Sprague Dawley
      rats were implanted with vascular catheters and administered lipopolysaccharide
      (LPS; 150 microg kg(-1) h(-1)) intravenously for 2 h, 6 h or 24 h (saline
      administered control animals were also included), after which the extensor
      digitorum longus (EDL) and myocardium were removed under terminal anaesthesia.
      The protein-to-DNA ratio, a marker of protein content, was significantly reduced
      in the EDL following 24 h LPS administration (23%; P<0.05), but was no different
      from controls in the myocardium. At the same time point, a significant increase
      in MAFbx/atrogin-1 and MuRF1 mRNA (3.7+/-0.7- and 19.5+/-1.9-fold increase vs.
      controls, respectively; P<0.05), in addition to protein levels of alpha1-3, 5-7
      subunits of the 20S proteasome, were observed in EDL but not myocardium. In
      contrast, elevations in phosphorylation of p70 S6K residues Thr(421)/Ser(424),
      and 4E-BP1 residues Thr(37)/Thr(46) (P<0.05), consistent with an elevation in
      translation initiation, were seen exclusively in the myocardium of LPS-treated
      animals. CONCLUSIONS/SIGNIFICANCE: In summary, these findings suggest that the
      myocardium does not undergo the same catabolic response as skeletal muscle during
      early endotoxaemia, partly due to the absence of transcriptional and signalling
      events in the myocardium typically associated with increased muscle proteolysis
      and the suppression of protein synthesis.

PMID- 19759898
TI  - High prevalence of Methanobrevibacter smithii and Methanosphaera stadtmanae
      detected in the human gut using an improved DNA detection protocol.
AB  - BACKGROUND: The low and variable prevalence of Methanobrevibacter smithii and
      Methanosphaera stadtmanae DNA in human stool contrasts with the paramount role of
      these methanogenic Archaea in digestion processes. We hypothesized that this
      contrast is a consequence of the inefficiencies of current protocols for archaeon
      DNA extraction. We developed a new protocol for the extraction and PCR-based
      detection of M. smithii and M. stadtmanae DNA in human stool.
      METHODOLOGY/PRINCIPAL FINDINGS: Stool specimens collected from 700 individuals
      were filtered, mechanically lysed twice, and incubated overnight with proteinase
      K prior to DNA extraction using a commercial DNA extraction kit. Total DNA was
      used as a template for quantitative real-time PCR targeting M. smithii and M.
      stadtmanae 16S rRNA and rpoB genes. Amplification of 16S rRNA and rpoB yielded
      positive detection of M. smithii in 95.7% and M. stadtmanae in 29.4% of
      specimens. Sequencing of 16S rRNA gene PCR products from 30 randomly selected
      specimens (15 for M. smithii and 15 for M. stadtmanae) yielded a sequence
      similarity of 99-100% using the reference M. smithii ATCC 35061 and M. stadtmanae
      DSM 3091 sequences. CONCLUSIONS/SIGNIFICANCE: In contrast to previous reports,
      these data indicate a high prevalence of the methanogens M. smithii and M.
      stadtmanae in the human gut, with the former being an almost ubiquitous
      inhabitant of the intestinal microbiome.

PMID- 19759899
TI  - Zebrafish IGF genes: gene duplication, conservation and divergence, and novel
      roles in midline and notochord development.
AB  - Insulin-like growth factors (IGFs) are key regulators of development, growth, and
      longevity. In most vertebrate species including humans, there is one IGF-1 gene
      and one IGF-2 gene. Here we report the identification and functional
      characterization of 4 distinct IGF genes (termed as igf-1a, -1b, -2a, and -2b) in
      zebrafish. These genes encode 4 structurally distinct and functional IGF
      peptides. IGF-1a and IGF-2a mRNAs were detected in multiple tissues in adult
      fish. IGF-1b mRNA was detected only in the gonad and IGF-2b mRNA only in the
      liver. Functional analysis showed that all 4 IGFs caused similar developmental
      defects but with different potencies. Many of these embryos had fully or
      partially duplicated notochords, suggesting that an excess of IGF signaling
      causes defects in the midline formation and an expansion of the notochord. IGF
      2a, the most potent IGF, was analyzed in depth. IGF-2a expression caused defects
      in the midline formation and expansion of the notochord but it did not alter the
      anterior neural patterning. These results not only provide new insights into the
      functional conservation and divergence of the multiple igf genes but also reveal
      a novel role of IGF signaling in midline formation and notochord development in a
      vertebrate model.

PMID- 19759900
TI  - Pertussis toxin stimulates IL-17 production in response to Bordetella pertussis
      infection in mice.
AB  - In a mouse model of respiratory tract infection by Bordetella pertussis, bacteria
      multiply in the airways over the first week and are then cleared over the next 3
      4 weeks by the host immune response. Pertussis toxin (PT), a virulence factor
      secreted exclusively by B. pertussis, promotes bacterial growth in the airways by
      suppression and modulation of host immune responses. By comparison of wild type
      and PT-deficient strains, we examined the role of PT in modulating airway
      cytokine and chemokine responses affecting neutrophil recruitment during B.
      pertussis infection in mice. We found that, despite early inhibition of
      neutrophil recruitment by PT, high numbers of neutrophils were recruited to the
      airways by 4 days post-infection with the wild type strain, but not with the PT
      deficient strain, and that this correlated with upregulation of neutrophil
      attracting chemokine gene expression. In addition, there was similar upregulation
      of genes expressing the cytokines IL-17A (IL-17), TNF-alpha and IFN-gamma,
      indicating a mixed Th1/Th17 response. Expression of IL-6, a cytokine involved in
      Th17 induction, was upregulated earlier than the IL-17 response. We showed that
      PT, rather than bacterial numbers, was important for induction of these
      responses. Flow cytometric analysis revealed that the IL-17-producing cells were
      macrophages and neutrophils as well as T cells, and were present predominantly in
      the airways rather than the lung tissue. Antibody neutralization of IL-17
      significantly reduced chemokine gene expression and neutrophil recruitment to the
      airways, but only modestly increased peak bacterial loads. These data indicate
      that PT stimulates inflammatory responses by induction of Th1- and Th17
      associated cytokines, including IL-17, during B. pertussis infection in mice, but
      a role for IL-17 in protection against the infection remains to be established.

PMID- 19759901
TI  - Anti-leukemia activity of MS-275 histone deacetylase inhibitor implicates 4
      1BBL/4-1BB immunomodulatory functions.
AB  - Histone deacetylase inhibitors (HDACi) have demonstrated promising therapeutic
      potential in clinical trials for hematological malignancies. HDACi, such as
      SAHA/Vorinostat, Trichostatin A, and MS-275 were found to induce apoptosis of
      leukemic blasts through activation of the death receptor pathway and
      transcriptional induction of the Tumor Necrosis Factor (TNF)-related pro
      apoptotic family members, TRAIL and FasL. The impact of HDACi on TNF-related
      costimulatory molecules such as 4-1BB ligand (4-1BBL/TNFSF9) is however not
      known. Following exposure to SAHA/Vorinostat, Trichostatin A, and MS-275,
      transcript levels were determined by real time PCR in Jurkat, Raji and U937
      cells. Treatment with HDACi up-regulated TNFSF9 gene expression in the three
      leukemia cell lines, yet to different extend and with distinct kinetics, which
      did not require de novo protein synthesis and was not associated with DNAse I
      hypersensitive chromatin remodeling. Transcriptional activity of TNFSF9 promoter
      luciferase constructs was induced up to 12 fold by HDACi, and implication of
      Sp1/Sp3 transcription factors binding to functional GC-box elements was evidenced
      by reporter gene assays, site-directed mutagenesis, and electrophoretic mobility
      shift assays. Functionality of modulated target genes was assessed in allogeneic
      mixed leukocyte reaction experiments. MS-275- and to a lesser extent Trichostatin
      A- and SAHA-treated Raji cells significantly up regulated T lymphocytes
      proliferation which was reduced by about 50% by a 4-1BB blocking recombinant
      protein, while MS-275- but neither Trichostatin A- nor SAHA-treated cells up
      regulated IFNgamma secretion by T lymphocytes. Our results identify 4-1BBL/4-1BB
      as a downstream target of HDACi, especially of MS-275 anti-leukemia action in
      vitro. Thus, HDACi such as MS-275 displaying dual TNF-dependent proapoptotic and
      costimulatory activities might be favored for inclusion in HDACi-based anti
      cancer therapeutic strategies.

PMID- 19759902
TI  - Dopamine in motor cortex is necessary for skill learning and synaptic plasticity.
AB  - Preliminary evidence indicates that dopamine given by mouth facilitates the
      learning of motor skills and improves the recovery of movement after stroke. The
      mechanism of these phenomena is unknown. Here, we describe a mechanism by
      demonstrating in rat that dopaminergic terminals and receptors in primary motor
      cortex (M1) enable motor skill learning and enhance M1 synaptic plasticity.
      Elimination of dopaminergic terminals in M1 specifically impaired motor skill
      acquisition, which was restored upon DA substitution. Execution of a previously
      acquired skill was unaffected. Reversible blockade of M1 D1 and D2 receptors
      temporarily impaired skill acquisition but not execution, and reduced long-term
      potentiation (LTP) within M1, a form of synaptic plasticity critically involved
      in skill learning. These findings identify a behavioral and functional role of
      dopaminergic signaling in M1. DA in M1 optimizes the learning of a novel motor
      skill.

PMID- 19759903
TI  - SBDS expression and localization at the mitotic spindle in human myeloid
      progenitors.
AB  - BACKGROUND: Shwachman-Diamond Syndrome (SDS) is a hereditary disease caused by
      mutations in the SBDS gene. SDS is clinically characterized by pancreatic
      insufficiency, skeletal abnormalities and bone marrow dysfunction. The
      hematologic abnormalities include neutropenia, neutrophil chemotaxis defects, and
      an increased risk of developing Acute Myeloid Leukemia (AML). Although several
      studies have suggested that SBDS as a protein plays a role in ribosome
      processing/maturation, its impact on human neutrophil development and function
      remains to be clarified. METHODOLOGY/PRINCIPAL FINDINGS: We observed that SBDS
      RNA and protein are expressed in the human myeloid leukemia PLB-985 cell line and
      in human hematopoietic progenitor cells by quantitative RT-PCR and Western blot
      analysis. SBDS expression is downregulated during neutrophil differentiation.
      Additionally, we observed that the differentiation and proliferation capacity of
      SDS-patient bone marrow hematopoietic progenitor cells in a liquid
      differentiation system was reduced as compared to control cultures.
      Immunofluorescence analysis showed that SBDS co-localizes with the mitotic
      spindle and in vitro binding studies reveal a direct interaction of SBDS with
      microtubules. In interphase cells a perinuclear enrichment of SBDS protein which
      co-localized with the microtubule organizing center (MTOC) was observed. Also, we
      observed that transiently expressed SDS patient-derived SBDS-K62 or SBDS-C84
      mutant proteins could co-localize with the MTOC and mitotic spindle.
      CONCLUSIONS/SIGNIFICANCE: SBDS co-localizes with the mitotic spindle, suggesting
      a role for SBDS in the cell division process, which corresponds to the decreased
      proliferation capacity of SDS-patient bone marrow CD34(+) hematopoietic
      progenitor cells in our culture system and also to the neutropenia in SDS
      patients. A role in chromosome missegregation has not been clarified, since
      similar spatial and time-dependent localization is observed when patient-derived
      SBDS mutant proteins are studied. Thus, the increased risk of myeloid malignancy
      in SDS remains unexplained.

PMID- 19759904
TI  - Jak3 is involved in dendritic cell maturation and CCR7-dependent migration.
AB  - BACKGROUND: CCR7-mediated signalling is important for dendritic cell maturation
      and homing to the lymph nodes. We have previously demonstrated that Jak3
      participates in the signalling pathway of CCR7 in T lymphocytes. METHODOLOGY AND
      PRINCIPAL FINDINGS: Here, we used Jak3(-/-) mice to analyze the role of Jak3 in
      CCR7-mediated dendritic cells migration and function. First, we found no
      differences in the generation of DCs from Jak3(-/-) bone marrow progenitors, when
      compared to wild type cells. However, phenotypic analysis of the bone marrow
      derived DCs obtained from Jak3(-/-) mice showed reduced expression of co
      stimulatory molecules compared to wild type (Jak3(+/+)). In addition, when we
      analyzed the migration of Jak3(-/-) and Jak3(+/+) mature DCs in response to CCL19
      and CCL21 chemokines, we found that the absence of Jak3 results in impaired
      chemotactic responses both in vitro and in vivo. Moreover, lymphocyte
      proliferation and contact hypersensitivity experiments showed that DC-mediated T
      lymphocyte activation is reduced in the absence of Jak3. CONCLUSION/SIGNIFICANCE:
      Altogether, our data provide strong evidence that Jak3 is important for DC
      maturation, migration and function, through a CCR7-mediated signalling pathway.

PMID- 19759905
TI  - Evaluation and validation of a real-time PCR assay for detection and quantitation
      of human adenovirus 14 from clinical samples.
AB  - In 2007, the Centers for Disease Control and Prevention (CDC) reported that Human
      adenovirus type 14 (HAdV-14) infected 106 military personnel and was responsible
      for the death of one U.S. soldier at Lackland Air Force Base in Texas.
      Identification of the responsible adenovirus, which had not previously been seen
      in North America and for which rapid diagnostic tools were unavailable, required
      retrospective analysis at reference laboratories. Initial quarantine measures
      were also reliant on relatively slow traditional PCR analysis at other locations.
      To address this problem, we developed a real-time PCR assay that detects a 225
      base pair sequence in the HAdV-14a hexon gene. Fifty-one oropharyngeal swab
      specimens from the Naval Health Research Center, San Diego, CA and Advanced
      Diagnostic Laboratory, Lackland AFB, TX were used to validate the new assay. The
      described assay detected eight of eight and 19 of 19 confirmed HAdV-14a clinical
      isolates in two separate cohorts from respiratory disease outbreaks. The real
      time PCR assay had a wide dynamic range, detecting from 10(2) to 10(7) copies of
      genomic DNA per reaction. The assay did not cross-react with other adenoviruses,
      influenza, respiratory syncytial virus, or common respiratory tract bacteria. The
      described assay is easy to use, sensitive and specific for HAdV-14a in clinical
      throat swab specimens, and very rapid since turnaround time is less than four
      hours to obtain an answer.

PMID- 19759906
TI  - Myeloid cells contribute to tumor lymphangiogenesis.
AB  - The formation of new blood vessels (angiogenesis) and lymphatic vessels
      (lymphangiogenesis) promotes tumor outgrowth and metastasis. Previously, it has
      been demonstrated that bone marrow-derived cells (BMDC) can contribute to tumor
      angiogenesis. However, the role of BMDC in lymphangiogenesis has largely remained
      elusive. Here, we demonstrate by bone marrow transplantation/reconstitution and
      genetic lineage-tracing experiments that BMDC integrate into tumor-associated
      lymphatic vessels in the Rip1Tag2 mouse model of insulinoma and in the TRAMP-C1
      prostate cancer transplantation model, and that the integrated BMDC originate
      from the myelomonocytic lineage. Conversely, pharmacological depletion of tumor
      associated macrophages reduces lymphangiogenesis. No cell fusion events are
      detected by genetic tracing experiments. Rather, the phenotypical conversion of
      myeloid cells into lymphatic endothelial cells and their integration into
      lymphatic structures is recapitulated in two in vitro tube formation assays and
      is dependent on fibroblast growth factor-mediated signaling. Together, the
      results reveal that myeloid cells can contribute to tumor-associated lymphatic
      vessels, thus extending the findings on the previously reported role of
      hematopoietic cells in lymphatic vessel formation.

PMID- 19759907
TI  - High resolution genome-wide analysis of chromosomal alterations in Burkitt's
      lymphoma.
AB  - Additional chromosomal abnormalities are currently detected in Burkitt's
      lymphoma. They play major roles in the progression of BL and in prognosis. The
      genes involved remain elusive. A whole-genome oligonucleotide array CGH analysis
      correlated with karyotype and FISH was performed in a set of 27 Burkitt's
      lymphoma-derived cell lines and primary tumors. More than half of the 145 CNAs<2
      Mb were mapped to Mendelian CNVs, including GSTT1, glutathione s-transferase and
      BIRC6, an anti-apoptotic protein, possibly predisposing to some cancers. Somatic
      cell line-specific CNVs localized to the IG locus were consistently observed with
      the 244 K aCGH platform. Among 136 CNAs >2 Mb, gains were found in 1q (12/27),
      13q (7/27), 7q (6/27), 8q(4/27), 2p (3/27), 11q (2/27) and 15q (2/27). Losses
      were found in 3p (5/27), 4p (4/27), 4q (4/27), 9p (4/27), 13q (4/27), 6p (3/27),
      17p (3/27), 6q (2/27),11pterp13 (2/27) and 14q12q21.3 (2/27). Twenty one minimal
      critical regions (MCR), (range 0.04-71.36 Mb), were delineated in tumors and cell
      lines. Three MCRs were localized to 1q. The proximal one was mapped to
      1q21.1q25.2 with a 6.3 Mb amplicon (1q21.1q21.3) harboring BCA2 and PIAS3. In the
      other 2 MCRs, 1q32.1 and 1q44, MDM4 and AKT3 appeared as possible drivers of
      these gains respectively. The 13q31.3q32.1 <89.58-96.81> MCR contained an
      amplicon and ABCC4 might be the driver of this amplicon. The 40 Kb 2p16.1 <60.96
      61> MCR was the smallest gained MCR and specifically encompassed the REL oncogene
      which is already implicated in B cell lymphomas. The most frequently deleted MCR
      was 3p14.1 <60.43-60.53> that removed the fifth exon of FHIT. Further
      investigations which combined gene expression and functional studies are
      essential to understand the lymphomagenesis mechanism and for the development of
      more effective, targeted therapeutic strategies.

PMID- 19759908
TI  - Classical morphology of plants as an elementary instance of classical invariant
      theory.
AB  - It has long been known that structural chemistry shows an intriguing
      correspondence with Classical Invariant Theory (CIT). Under this view, an
      algebraic binary form of the degree n corresponds to a chemical atom with valence
      n and each physical molecule or ion has an invariant-theoretic counterpart. This
      theory was developed using the Aronhold symbolical approach and the symbolical
      processes of convolution/transvection in CIT was characterized as a potential
      "accurate morphological method". However, CIT has not been applied to the formal
      morphology of living organisms. Based on the morphological interpretation of
      binary form, as well as the process of convolution/transvection, the First and
      Second Fundamental Theorems of CIT and the Nullforms of CIT, we show how CIT can
      be applied to the structure of plants, especially when conceptualized as a series
      of plant metamers (phytomers). We also show that the weight of the
      covariant/invariant that describes a morphological structure is a criterion of
      simplicity and, therefore, we argue that this allows us to formulate a
      parsimonious method of formal morphology. We demonstrate that the "theory of
      axilar bud" is the simplest treatment of the grass seedling/embryo. Our
      interpretations also represent Troll's bauplan of the angiosperms, the principle
      of variable proportions, morphological misfits, the basic types of stem
      segmentation, and Goethe's principle of metamorphosis in terms of CIT. Binary
      forms of different degrees might describe any repeated module of plant organisms.
      As bacteria, invertebrates, and higher vertebrates are all generally shared a
      metameric morphology, wider implications of the proposed symmetry between CIT and
      formal morphology of plants are apparent.

PMID- 19759909
TI  - Something old, something new, something borrowed; how the thermoacidophilic
      archaeon Sulfolobus solfataricus responds to oxidative stress.
AB  - To avoid molecular damage of biomolecules due to oxidation, all cells have
      evolved constitutive and responsive systems to mitigate and repair chemical
      modifications. Archaea have adapted to some of the most extreme environments
      known to support life, including highly oxidizing conditions. However, in
      comparison to bacteria and eukaryotes, relatively little is known about the
      biology and biochemistry of archaea in response to changing conditions and repair
      of oxidative damage. In this study transcriptome, proteome, and chemical
      reactivity analyses of hydrogen peroxide (H(2)O(2)) induced oxidative stress in
      Sulfolobus solfataricus (P2) were conducted. Microarray analysis of mRNA
      expression showed that 102 transcripts were regulated by at least 1.5 fold, 30
      minutes after exposure to 30 microM H(2)O(2). Parallel proteomic analyses using
      two-dimensional differential gel electrophoresis (2D-DIGE), monitored more than
      800 proteins 30 and 105 minutes after exposure and found that 18 had significant
      changes in abundance. A recently characterized ferritin-like antioxidant protein,
      DPSL, was the most highly regulated species of mRNA and protein, in addition to
      being post-translationally modified. As expected, a number of antioxidant related
      mRNAs and proteins were differentially regulated. Three of these, DPSL,
      superoxide dismutase, and peroxiredoxin were shown to interact and likely form a
      novel supramolecular complex for mitigating oxidative damage. A scheme for the
      ability of this complex to perform multi-step reactions is presented. Despite the
      central role played by DPSL, cells maintained a lower level of protection after
      disruption of the dpsl gene, indicating a level of redundancy in the oxidative
      stress pathways of S. solfataricus. This work provides the first "omics" scale
      assessment of the oxidative stress response for an archeal organism and together
      with a network analysis using data from previous studies on bacteria and
      eukaryotes reveals evolutionarily conserved pathways where complex and
      overlapping defense mechanisms protect against oxygen toxicity.

PMID- 19759910
TI  - Climate change and the potential spreading of marine mucilage and microbial
      pathogens in the Mediterranean Sea.
AB  - BACKGROUND: Marine snow (small amorphous aggregates with colloidal properties) is
      present in all oceans of the world. Surface water warming and the consequent
      increase of water column stability can favour the coalescence of marine snow into
      marine mucilage, large marine aggregates representing an ephemeral and extreme
      habitat. Marine mucilage characterize aquatic systems with altered environmental
      conditions. METHODOLOGY/PRINCIPAL FINDINGS: We investigated, by means of
      molecular techniques, viruses and prokaryotes within the mucilage and in
      surrounding seawater to examine the potential of mucilage to host new microbial
      diversity and/or spread marine diseases. We found that marine mucilage contained
      a large and unexpectedly exclusive microbial biodiversity and hosted pathogenic
      species that were absent in surrounding seawater. We also investigated the
      relationship between climate change and the frequency of mucilage in the
      Mediterranean Sea over the last 200 years and found that the number of mucilage
      outbreaks increased almost exponentially in the last 20 years. The increasing
      frequency of mucilage outbreaks is closely associated with the temperature
      anomalies. CONCLUSIONS/SIGNIFICANCE: We conclude that the spreading of mucilage
      in the Mediterranean Sea is linked to climate-driven sea surface warming. The
      mucilage can act as a controlling factor of microbial diversity across wide
      oceanic regions and could have the potential to act as a carrier of specific
      microorganisms, thereby increasing the spread of pathogenic bacteria.

PMID- 19759911
TI  - PSSA-2, a membrane-spanning phosphoprotein of Trypanosoma brucei, is required for
      efficient maturation of infection.
AB  - The coat of Trypanosoma brucei consists mainly of glycosylphosphatidylinositol
      anchored proteins that are present in several million copies and are
      characteristic of defined stages of the life cycle. While these major components
      of the coats of bloodstream forms and procyclic (insect midgut) forms are well
      characterised, very little is known about less abundant stage-regulated surface
      proteins and their roles in infection and transmission. By creating epitope
      tagged versions of procyclic-specific surface antigen 2 (PSSA-2) we demonstrated
      that it is a membrane-spanning protein that is expressed by several different
      life cycle stages in tsetse flies, but not by parasites in the mammalian
      bloodstream. In common with other membrane-spanning proteins in T. brucei, PSSA-2
      requires its cytoplasmic domain in order to exit the endoplasmic reticulum.
      Correct localisation of PSSA-2 requires phosphorylation of a cytoplasmic
      threonine residue (T(305)), a modification that depends on the presence of
      TbMAPK4. Mutation of T(305) to alanine (T(305)A) has no effect on the
      localisation of the protein in cells that express wild type PSSA-2. In contrast,
      this protein is largely intracellular when expressed in a null mutant background.
      A variant with a T(305)D mutation gives strong surface expression in both the
      wild type and null mutant, but slows growth of the cells, suggesting that it may
      function as a dominant negative mutant. The PSSA-2 null mutant exhibits no
      perceptible phenotype in culture and is fully competent at establishing midgut
      infections in tsetse, but is defective in colonising the salivary glands and the
      production of infectious metacyclic forms. Given the protein's structure and the
      effects of mutation of T(305) on proliferation and localisation, we postulate
      that PSSA-2 might sense and transmit signals that contribute to the parasite's
      decision to divide, differentiate or migrate.

PMID- 19759912
TI  - Induction of epithelial mesenchimal transition and vasculogenesis in the lenses
      of Dbl oncogene transgenic mice.
AB  - BACKGROUND: The Dbl family of proteins represents a large group of proto
      oncogenes involved in cell growth regulation. The numerous domains that are
      present in many Dbl family proteins suggest that they act to integrate multiple
      inputs in complicated signaling networks involving the Rho GTPases. Alterations
      of the normal function of these proteins lead to pathological processes such as
      developmental disorders and neoplastic transformation. We generated transgenic
      mice introducing the cDNA of Dbl oncogene linked to the metallothionein promoter
      into the germ line of FVB mice and found that onco-Dbl expression in mouse lenses
      affected proliferation, migration and differentiation of lens epithelial cells.
      RESULTS: We used high density oligonucleotide microarray to define the
      transcriptional profile induced by Dbl in the lenses of 2 days, 2 weeks, and 6
      weeks old transgenic mice. We observed modulation of genes encoding proteins
      promoting epithelial-mesenchymal transition (EMT), such as down-regulation of
      epithelial cell markers and up-regulation of fibroblast markers. Genes encoding
      proteins involved in the positive regulation of apoptosis were markedly down
      regulated while anti-apoptotic genes were strongly up-regulated. Finally, several
      genes encoding proteins involved in the process of angiogenesis were up
      regulated. These observations were validated by histological and
      immunohistochemical examination of the transgenic lenses where vascularization
      can be readily observed. CONCLUSION: Onco-Dbl expression in mouse lens correlated
      with modulation of genes involved in the regulation of EMT, apoptosis and
      vasculogenesis leading to disruption of the lens architecture, epithelial cell
      proliferation, and aberrant angiogenesis. We conclude that onco-Dbl has a
      potentially important, previously unreported, capacity to dramatically alter
      epithelial cell migration, replication, polarization and differentiation and to
      induce vascularization of an epithelial tissue.

PMID- 19759913
TI  - Barrier-to-autointegration factor proteome reveals chromatin-regulatory partners.
AB  - Nuclear lamin filaments and associated proteins form a nucleoskeletal ("lamina")
      network required for transcription, replication, chromatin organization and
      epigenetic regulation in metazoans. Lamina defects cause human disease
      ("laminopathies") and are linked to aging. Barrier-to-autointegration factor
      (BAF) is a mobile and essential component of the nuclear lamina that binds
      directly to histones, lamins and LEM-domain proteins, including the inner nuclear
      membrane protein emerin, and has roles in chromatin structure, mitosis and gene
      regulation. To understand BAF's mechanisms of action, BAF associated proteins
      were affinity-purified from HeLa cell nuclear lysates using BAF-conjugated beads,
      and identified by tandem mass spectrometry or independently identified and
      quantified using the iTRAQ method. We recovered A- and B-type lamins and core
      histones, all known to bind BAF directly, plus four human transcription factors
      (Requiem, NonO, p15, LEDGF), disease-linked proteins (e.g., Huntingtin, Treacle)
      and several proteins and enzymes that regulate chromatin. Association with
      endogenous BAF was independently validated by co-immunoprecipitation from HeLa
      cells for seven candidates including Requiem, poly(ADP-ribose) polymerase 1
      (PARP1), retinoblastoma binding protein 4 (RBBP4), damage-specific DNA binding
      protein 1 (DDB1) and DDB2. Interestingly, endogenous BAF and emerin each
      associated with DDB2 and CUL4A in a UV- and time-dependent manner, suggesting BAF
      and emerin have dynamic roles in genome integrity and might help couple DNA
      damage responses to the nuclear lamina network. We conclude this proteome is a
      rich source of candidate partners for BAF and potentially also A- and B-type
      lamins, which may reveal how chromatin regulation and genome integrity are linked
      to nuclear structure.

PMID- 19759914
TI  - A family of diverse Kunitz inhibitors from Echinococcus granulosus potentially
      involved in host-parasite cross-talk.
AB  - The cestode Echinococcus granulosus, the agent of hydatidosis/echinococcosis, is
      remarkably well adapted to its definitive host. However, the molecular mechanisms
      underlying the successful establishment of larval worms (protoscoleces) in the
      dog duodenum are unknown. With the aim of identifying molecules participating in
      the E. granulosus-dog cross-talk, we surveyed the transcriptomes of protoscoleces
      and protoscoleces treated with pepsin at pH 2. This analysis identified a
      multigene family of secreted monodomain Kunitz proteins associated mostly with
      pepsin/H(+)-treated worms, suggesting that they play a role at the onset of
      infection. We present the relevant molecular features of eight members of the E.
      granulosus Kunitz family (EgKU-1 - EgKU-8). Although diverse, the family includes
      three pairs of close paralogs (EgKU-1/EgKU-4; EgKU-3/EgKU-8; EgKU-6/EgKU-7),
      which would be the products of recent gene duplications. In addition, we describe
      the purification of EgKU-1 and EgKU-8 from larval worms, and provide data
      indicating that some members of the family (notably, EgKU-3 and EgKU-8) are
      secreted by protoscoleces. Detailed kinetic studies with native EgKU-1 and EgKU-8
      highlighted their functional diversity. Like most monodomain Kunitz proteins,
      EgKU-8 behaved as a slow, tight-binding inhibitor of serine proteases, with
      global inhibition constants (K(I) (*)) versus trypsins in the picomolar range. In
      sharp contrast, EgKU-1 did not inhibit any of the assayed peptidases.
      Interestingly, molecular modeling revealed structural elements associated with
      activity in Kunitz cation-channel blockers. We propose that this family of
      inhibitors has the potential to act at the E. granulosus-dog interface and
      interfere with host physiological processes at the initial stages of infection.

PMID- 19759915
TI  - Variants in neuropeptide Y receptor 1 and 5 are associated with nutrient-specific
      food intake and are under recent selection in Europeans.
AB  - There is a large variation in caloric intake and macronutrient preference between
      individuals and between ethnic groups, and these food intake patterns show a
      strong heritability. The transition to new food sources during the agriculture
      revolution around 11,000 years ago probably created selective pressure and shaped
      the genome of modern humans. One major player in energy homeostasis is the
      appetite-stimulating hormone neuropeptide Y, in which the stimulatory capacity
      may be mediated by the neuropeptide Y receptors 1, 2 and 5 (NPY1R, NPY2R and
      NPY5R). We assess association between variants in the NPY1R, NPY2R and NPY5R
      genes and nutrient intake in a cross-sectional, single-center study of 400 men
      aged 40 to 80 years, and we examine whether genomic regions containing these
      genes show signatures of recent selection in 270 HapMap individuals (90 Africans,
      90 Asians, and 90 Caucasians) and in 846 Dutch bloodbank controls. Our results
      show that derived alleles in NPY1R and NPY5R are associated with lower
      carbohydrate intake, mainly because of a lower consumption of mono- and
      disaccharides. We also show that carriers of these derived alleles, on average,
      consume meals with a lower glycemic index and glycemic load and have higher
      alcohol consumption. One of these variants shows the hallmark of recent selection
      in Europe. Our data suggest that lower carbohydrate intake, consuming meals with
      a low glycemic index and glycemic load, and/or higher alcohol consumption, gave a
      survival advantage in Europeans since the agricultural revolution. This advantage
      could lie in overall health benefits, because lower carbohydrate intake,
      consuming meals with a low GI and GL, and/or higher alcohol consumption, are
      known to be associated with a lower risk of chronic diseases.

PMID- 19759916
TI  - Molecular phylogeny and description of the novel katablepharid Roombia truncata
      gen. et sp. nov., and establishment of the Hacrobia taxon nov.
AB  - BACKGROUND: Photosynthetic eukaryotes with a secondary plastid of red algal
      origin (cryptophytes, haptophytes, stramenopiles, dinoflagellates, and
      apicomplexans) are hypothesized to share a single origin of plastid acquisition
      according to Chromalveolate hypothesis. Recent phylogenomic analyses suggest that
      photosynthetic "chromalveolates" form a large clade with inclusion of several non
      photosynthetic protist lineages. Katablepharids are one such non-photosynthetic
      lineage closely related to cryptophytes. Despite their evolutionary and
      ecological importance, katablepharids are poorly investigated.
      METHODOLOGY/PRINCIPAL FINDINGS: Here, we report a newly discovered flagellate,
      Roombia truncata gen. et sp. nov., that is related to katablepharids, but is
      morphologically distinct from othermembers of the group in the following ways:
      (1) two flagella emerge from a papilla-like subapical protrusion, (2) conspicuous
      ejectisomes are aligned in multiple (5-11) rows, (3) each ejectisome increases in
      size towards the posterior end of the rows, and (4) upon feeding, a part of
      cytoplasm elastically stretch to engulf whole prey cell. Molecular phylogenies
      inferred from Hsp90, SSU rDNA, and LSU rDNA sequences consistently and strongly
      show R. truncata as the sister lineage to all other katablepharids, including
      lineages known only from environmental sequence surveys. A close association
      between katablepharids and cryptophytes was also recovered in most analyses.
      Katablepharids and cryptophytes are together part of a larger, more inclusive,
      group that also contains haptophytes, telonemids, centrohelids and perhaps
      biliphytes. The monophyly of this group is supported by several different
      molecular phylogenetic datasets and one shared lateral gene transfer; therefore,
      we formally establish this diverse clade as the "Hacrobia."
      CONCLUSIONS/SIGNIFICANCE: Our discovery of R. truncata not only expands our
      knowledge in the less studied flagellate group, but provide a better
      understanding of phylogenetic relationship and evolutionary view of plastid
      acquisition/losses of Hacrobia. Being an ancestral to all katablepharids, and
      readily cultivable, R. truncata is a good candidate for multiple gene analyses
      that will contribute to future phylogenetic studies of Hacrobia.

PMID- 19759917
TI  - Prodepth: predict residue depth by support vector regression approach from
      protein sequences only.
AB  - Residue depth (RD) is a solvent exposure measure that complements the information
      provided by conventional accessible surface area (ASA) and describes to what
      extent a residue is buried in the protein structure space. Previous studies have
      established that RD is correlated with several protein properties, such as
      protein stability, residue conservation and amino acid types. Accurate prediction
      of RD has many potentially important applications in the field of structural
      bioinformatics, for example, facilitating the identification of functionally
      important residues, or residues in the folding nucleus, or enzyme active sites
      from sequence information. In this work, we introduce an efficient approach that
      uses support vector regression to quantify the relationship between RD and
      protein sequence. We systematically investigated eight different sequence
      encoding schemes including both local and global sequence characteristics and
      examined their respective prediction performances. For the objective evaluation
      of our approach, we used 5-fold cross-validation to assess the prediction
      accuracies and showed that the overall best performance could be achieved with a
      correlation coefficient (CC) of 0.71 between the observed and predicted RD values
      and a root mean square error (RMSE) of 1.74, after incorporating the relevant
      multiple sequence features. The results suggest that residue depth could be
      reliably predicted solely from protein primary sequences: local sequence
      environments are the major determinants, while global sequence features could
      influence the prediction performance marginally. We highlight two examples as a
      comparison in order to illustrate the applicability of this approach. We also
      discuss the potential implications of this new structural parameter in the field
      of protein structure prediction and homology modeling. This method might prove to
      be a powerful tool for sequence analysis.

PMID- 19759919
TI  - Insights into electron tunneling across hydrogen-bonded base-pairs in complete
      molecular circuits for single-stranded DNA sequencing.
AB  - We report a first-principles study of electron ballistic transport through a
      molecular junction containing deoxycytidine-monophosphate (dCMP) connected to
      metal electrodes. A guanidinium ion and guanine nucleobase are tethered to gold
      electrodes on opposite sides to form hydrogen bonds with the dCMP molecule
      providing an electric circuit. The circuit mimics a component of a potential
      device for sequencing unmodified single-stranded DNA. The molecular conductance
      is obtained from DFT Green's function scattering methods and is compared to
      estimates from the electron tunneling decay constant obtained from the complex
      band structure. The result is that a complete molecular dCMP circuit of
      'linker((CH(2))(2))-guanidinium-phosphate-deoxyribose-cytosine-guanine' has a
      very low conductance (of the order of fS) while the hydrogen-bonded guanine
      cytosine base-pair has a moderate conductance (of the order of tens to hundreds
      of nS). Thus, while the transverse electron transfer through base-pairing is
      moderately conductive, electron transfer through a complete molecular dCMP
      circuit is not. The gold Fermi level is found to be aligned very close to the
      HOMO for both the guanine-cytosine base-pair and the complete molecular dCMP
      circuit. Results for two different plausible geometries of the hydrogen-bonded
      dCMP molecule reveal that the conductance varies from fS for an extended
      structure to pS for a slightly compressed structure.

PMID- 19759918
TI  - An evolutionary perspective of animal microRNAs and their targets.
AB  - MicroRNAs (miRNAs) are short noncoding RNAs that regulate gene expression through
      translational inhibition or mRNA degradation by binding to sequences on the
      target mRNA. miRNA regulation appears to be the most abundant mode of
      posttranscriptional regulation affecting approximately 50% of the transcriptome.
      miRNA genes are often clustered and/or located in introns, and each targets a
      variable and often large number of mRNAs. Here we discuss the genomic
      architecture of animal miRNA genes and their evolving interaction with their
      target mRNAs.

PMID- 19759920
TI  - The 'PREXCEL-Q Method' for qPCR.
AB  - The purpose of this manuscript is to describe a reliable approach to quantitative
      real-time polymerase chain reaction (qPCR) assay development and project
      management, which is currently embodied in the Excel 2003-based software program
      named "PREXCEL-Q" (P-Q) (formerly known as "FocusField2-6Gallup-qPCRSet-upTool
      001," "FF2-6-001 qPCR set-up tool" or "Iowa State University Research Foundation
      [ISURF] project #03407"). Since its inception from 1997-2007, the program has
      been well-received and requested around the world and was recently unveiled by
      its inventor at the 2008 Cambridge Healthtech Institute's Fourth Annual qPCR
      Conference in San Diego, CA. P-Q was subsequently mentioned in a review article
      by Stephen A. Bustin, an acknowledged leader in the qPCR field. Due to its
      success and growing popularity, and the fact that P-Q introduces a unique/defined
      approach to qPCR, a concise description of what the program is and what it does
      has become important. Sample-related inhibitory problems of the qPCR assay,
      sample concentration limitations, nuclease-treatment, reverse transcription (RT)
      and master mix formulations are all addressed by the program, enabling
      investigators to quickly, consistently and confidently design uninhibited,
      dynamically-sound, LOG-linear-amplification-capable, high-efficiency-of
      amplification reactions for any type of qPCR. The current version of the program
      can handle an infinite number of samples.

PMID- 19759922
TI  - Potassium channels in brain mitochondria.
AB  - Potassium channels are the most widely distributed class of ion channels. These
      channels are transmembrane proteins known to play important roles in both normal
      and pathophysiological functions in all cell types. Various potassium channels
      are recognised as potential therapeutic targets in the treatment of Parkinson's
      disease, Alzheimer's disease, brain/spinal cord ischaemia and sepsis. In addition
      to their importance as therapeutic targets, certain potassium channels are known
      for their beneficial roles in anaesthesia, cardioprotection and neuroprotection.
      Some types of potassium channels present in the plasma membrane of various cells
      have been found in the inner mitochondrial membrane as well. Potassium channels
      have been proposed to regulate mitochondrial membrane potential, respiration,
      matrix volume and Ca(+) ion homeostasis. It has been proposed that mitochondrial
      potassium channels mediate ischaemic preconditioning in various tissues. However,
      the specificity of a pharmacological agents and the mechanisms underlying their
      effects on ischaemic preconditioning remain controversial. The following
      potassium channels from various tissues have been identified in the inner
      mitochondrial membrane: ATP-regulated (mitoK(ATP)) channel, large conductance
      Ca(2+)-regulated (mitoBK(Ca)) channel, intermediate conductance Ca(2+)-regulated
      (mitoIK(Ca)) channel, voltage-gated (mitoKv1.3 type) channel, and twin-pore
      domain (mitoTASK-3) channel. It has been shown that increased potassium flux into
      brain mitochondria induced by either the mitoK(ATP) channel or mitoBK(Ca) channel
      affects the beneficial effects on neuronal cell survival under pathological
      conditions. Recently, differential distribution of mitoBK(Ca) channels has been
      observed in neuronal mitochondria. These findings may suggest a neuroprotective
      role for the mitoBK(Ca) channel in specific brain structures. This minireview
      summarises current data on brain mitochondrial potassium channels and the efforts
      to identify their molecular correlates.

PMID- 19759923
TI  - High sequence homology between protein tyrosine acid phosphatase from boar
      seminal vesicles and human prostatic acid phosphatase.
AB  - Boar seminal vesicle protein tyrosine acid phosphatase (PTAP) and human prostatic
      acid phosphatase (PAP) show high affinity for protein phosphotyrosine residues.
      The physico-chemical and kinetic properties of the boar and human enzymes are
      different. The main objective of this study was to establish the nucleotide
      sequence of cDNA encoding boar PTAP and compare it with that of human PAP cDNA.
      Also, the amino-acid sequence of boar PTAP was compared with the sequence of
      human PAP. PTAP was isolated from boar seminal vesicle fluid and sequenced. cDNA
      to boar seminal vesicle RNA was synthesized, amplified by PCR, cloned in E. coli
      and sequenced. The obtained N-terminal amino-acid sequence of boar PTAP showed
      92% identity with the N-terminal amino-acid sequence of human PAP. The determined
      sequence of a 354 bp nucleotide fragment (GenBank accession number: GQ184596)
      showed 90% identity with the corresponding sequence of human PAP. On the basis of
      this sequence a 118 amino acid fragment of boar PTAP was predicted. This fragment
      showed 89% identity with the corresponding fragment of human PAP and had a
      similar hydropathy profile. The compared sequences differ in terms of their
      isoelectric points and amino-acid composition. This may explain the differences
      in substrate specificity and inhibitor resistance of boar PTAP and human PAP.

PMID- 19759926
TI  - [NiFe] hydrogenases: structural and spectroscopic studies of the reaction
      mechanism.
AB  - [NiFe] hydrogenases catalyze the reversible oxidation of dihydrogen. For this
      simple reaction the molecule has developed a complex catalytic mechanism, during
      which the enzyme passes through various redox states. The [NiFe] hydrogenase
      contains several metal centres, including the bimetallic Ni-Fe active site, iron
      sulfur clusters and a Mg(2+) ion. The Ni-Fe active site is located in the inner
      part of the protein molecule, therefore a number of pathways are involved in the
      catalytic reaction route. These consist of an electron transfer pathway, a proton
      transfer pathway and a gas-access channel. Over the last 10-15 years we have been
      investigating the crystal structures of the [NiFe] hydrogenase from Desulfovibrio
      vulgaris Miyazaki F, which is a sulfate-reducing anaerobic bacterium. So far the
      crystal structures of the oxidized, H(2)-reduced and carbon monoxide inhibited
      states have been determined at high resolution and have revealed a rather unique
      structure of the hetero-bimetallic Ni-Fe active site. Furthermore, intensive
      spectroscopic studies have been performed on the enzyme. Based on the crystal
      structure, a water-soluble Ni-Ru complex has been synthesized as a functional
      model for the [NiFe] hydrogenases. The present review gives an overview of the
      catalytic reaction mechanism of the [NiFe] hydrogenases.

PMID- 19759927
TI  - A categorization of metal anticancer compounds based on their mode of action.
AB  - The development of new metal anticancer compounds is a challenge for inorganic
      chemists. We have to face the fact that four decades of research in this field
      have only produced a small number of clinically used compounds, most often
      developed through serendipity rather than through rational chemical design.
      Nevertheless, by virtue of the wealth of knowledge acquired in these years,
      medicinal inorganic chemistry is probably mature for making significant steps
      forward and there are great expectations for future developments. With the aim of
      contributing to the rationalization of this field, we suggest here a
      categorization of metal anticancer compounds into five classes based on their
      mode of action: (i) the metal has a functional role, i.e. it must bind to the
      biological target; (ii) the metal has a structural role, i.e. it is instrumental
      in determining the shape of the compound and binding to the biological target
      occurs through non-covalent interactions; (iii) the metal is a carrier for active
      ligands that are delivered in vivo; (iv) the metal compound is a catalyst; and
      (v) the metal compound is photoactive and behaves as a photo-sensitizer. Selected
      examples for each category are given. The few metal anticancer drugs that are in
      clinical use are all believed to be functional compounds. Our classification,
      that is clearly focused on the metal compound and is independent from the nature
      of its bio-target(s)-most often still unknown-has the purpose of providing an
      intellectual tool that might be helpful in the rational development of new drugs.

PMID- 19759928
TI  - Three-component assembly of a metal-inorganic 3D Co(II) polymer containing
      bridging hydrazine.
AB  - Three-component metal-inorganic assembly of a Co(ii) network representing the
      first example of a 3D coordination polymer containing a hydrazine bridging
      ligand, has been synthesized and characterized.

PMID- 19759929
TI  - Evidence for heterogeneous Sonogashira coupling of phenylacetylene and
      iodobenzene catalyzed by well defined rhodium nanoparticles.
AB  - Sonogashira coupling of phenylacetylene with iodobenzene has been studied in the
      presence of metallic Rh nanoparticle catalysts and found to occur via a surface
      mediated heterogeneous route. Homogeneous catalytic processes due to Rh species
      that may leach into solution were barely detectable within the sensitivity of our
      experiments. Moreover, larger (8 nm) nanoparticles were found to be much better
      catalysts than very small ones (2 nm), which is consistent with the hypothesis
      that steric limitations adversely affect the efficiency of the latter.

PMID- 19759930
TI  - Ethanol electrooxidation on Pt/C catalysts promoted with praseodymium oxide
      nanorods.
AB  - The Pt/C electrocatalysts containing Pr(6)O(11) nanorods were successfully
      prepared. By various electrochemical characterization methods, it was
      demonstrated that the Pr(6)O(11) nanorods have an obviously promotive role for
      ethanol electrooxidation catalyzed by Pt/C. However, according to the stripping
      experiment, the promotive effect of Pr(6)O(11) does not result from the easier
      electrooxidation of the intermediate adsorbate on Pt-Pr(6)O(11)/C than on Pt/C.
      It was supposed that Pr(6)O(11) could promote a certain step in ethanol
      oxidation, and that the special morphology of the nanorods could further enhance
      the activity compared with nanoparticles.

PMID- 19759931
TI  - Isolation and structures of sulfonium salts derived from thioethers: [{o
      C(6)H(4)(CH(2)SMe)(2)}H][NbF(6)] and [{[9]aneS(3)}H][NbF(6)].
AB  - Two very unusual sulfonium salts, [{o-C(6)H(4)(CH(2)SMe)(2)}H][NbF(6)] and
      [{[9]aneS(3)}H][NbF(6)], obtained from reaction of the thioethers with NbF(5) in
      CH(2)Cl(2) solution, are reported and their structures described; the eight
      coordinate tetrafluoro Nb(v) cation of the dithioether is obtained from the same
      reaction.

PMID- 19759932
TI  - First reductive dimerization of a polycyclic azine.
AB  - The tptz molecule is reduced by potassium into its anion-radical in the compound
      K(tptz)(2) (), whereas it is reductively coupled by SmI(2) and UI(3)(py)(4) into
      the bis-triazinide ligand in the dinuclear complexes [Sm(2)(tptz
      tptz)(DMF)(8)][I](4).3.5DMF (.3.5DMF) and U(2)I(6)(tptz-tptz)(MeCN)(2).2MeCN
      (.2MeCN) where each metal ion occupies a pentadentate N(5) cavity of the [tptz
      tptz](2-) ligand.

PMID- 19759933
TI  - Robust recognition of malonate and 2-amino-4-picolinium in conjunction with M(II)
      as a triad (M = Ni/Co/Mn): role of this highly stable hydrogen-bonded motif in
      driving supramolecular self-assembly.
AB  - The crystal lattice of the three isostructural compounds ,
      (C(6)H(8)N(2)H)(2)[M(C(3)H(2)O(4))(2)(H(2)O)(2)].4H(2)O (C(6)H(8)N(2)H =
      protonated 2-amino-4-picoline, M = Ni/Co/Mn, C(3)H(4)O(4) = malonate dianion;
      hereafter, malonate) is formed by supramolecular 2D layers. Hydrogen-bonding,
      pi...pi and lone pair...pi interactions play crucial role in organizing monomeric
      [M(II)(mal)(2)(H(2)O)(2)] units into 2D sheets along the ab plane, through the
      self-association between two different supramolecular building blocks, namely a
      tetrameric water cluster including metal-coordinated water molecules, and
      R(2)(2)(8) and R(2)(2)(7) hydrogen-bonded recognition synthons between 2-amino-4
      picolinium and malonate. DFT calculations clearly show that the robust 2-amino-4
      picolinium/malonate hydrogen-bonded motif drives the self-assembly of the
      supramolecular network observed.

PMID- 19759934
TI  - In search for tuneable intramolecular intermetallic interactions in polynuclear
      lanthanide complexes.
AB  - Reaction of unsymmetrical tridentate 2-benzimidazolyl-6-carboxamidopyridine
      binding units in the ligands (b) and with neutral Ln(NO(3))(3) (Ln is a trivalent
      lanthanide) gives mononuclear [Ln((b))(NO(3))(3)(solvent)] and binuclear
      [Ln(2)(L5)(NO(3))(6)(solvent)(2)] complexes. The crystal structures of (b) and
      [Eu((b))(NO(3))(3)(CH(3)CN)] unravel the conformational change of the tridentate
      binding units required for its coordination to the metal, a process responsible
      for the change in electronic absorption spectra and in (1)H NMR spectra recorded
      in acetonitrile solution. In the solid state, the bis-tridentate ligand shows
      variable helical conformations of its central diphenylmethane spacer in its
      uncoordinated form (amphiverse helix) and in its complexed form in
      [Eu(2)(L5)(NO(3))(6)(H(2)O)(2)] (regular helix), which puts the two metals at a
      contact distance of 8.564(1) A. In solution, fast rearrangements yield an average
      planar extended conformation of the spacer, which increases the intramolecular
      intermetallic contact distance by 30% in [Ln(2)(L5)(NO(3))(6)(H(2)O)(2)].
      Surprisingly, the thermodynamic analysis of the complexation processes in
      solution points to unusual, and to some extent non-predicted charge effects
      because the intramolecular intermetallic repulsive interaction measured in the
      neutral complex [Ln(2)(L5)(NO(3))(6)] (Ln...Ln approximately 12 A) is comparable
      with that found in the highly charged triple-stranded helicate [Ln(2)(L5)(3)](6+)
      (Ln...Ln approximately 9 A). The origin of this effect and its consequences on
      programming stable polynuclear complexes is discussed.

PMID- 19759935
TI  - Structural diversity of benzil bis(benzoylhydrazone): Mononuclear, binuclear and
      trinuclear complexes.
AB  - The coordination behaviour of the Schiff-base, benzil bis(benzoylhydrazone),
      LH(2) towards divalent nickel, lead, cadmium, zinc and copper ions has been
      investigated. The complexes have been fully characterized by techniques including
      (113)Cd and (207)Pb NMR, as well as (13)C and (113)Cd CP/MAS NMR and by single
      crystal X-ray diffraction. All the complexes have the general formula [ML](n) (n
      = 1-3 depending on the metal ion), with the ligand doubly deprotonated. The
      nickel complex [NiL] is a monomeric compound, the lead complex [PbL](2) shows a
      binuclear structure, whereas zinc [ZnL](3) and copper [CuL](3) complexes are
      trinuclear helicates. The cadmium complex seems to be a dimer with a structure
      similar to that of . In the nickel and lead derivatives, the ligand behaves as a
      tetradentate N(2)O(2) chelate and in complex also as a bridge through one of the
      O atoms. In the crystal structures of Zn and Cu complexes [ML](3) each metal is
      in a pentadentate N(3)O(2) environment formed by two different ligands, one
      tridentate chelate and the other bidentate chelate, giving rise to trinuclear
      helicates. These results point out the versatility of benzil
      bis(benzoylhydrazone) on its coordination.

PMID- 19759936
TI  - Synthesis and catalytic activity of an electron-deficient copper-ethylene
      triazapentadienyl complex.
AB  - The copper(i) ethylene complex [N{(C(3)F(7))C(Dipp)N}(2)]Cu(C(2)H(4)) (Dipp = 2,6
      diisopropylphenyl) has been synthesized by treating
      [N{(C(3)F(7))C(Dipp)N}(2)]Cu(NCCH(3)) with ethylene at room temperature.
      [N{(C(3)F(7))C(Dipp)N}(2)]Cu(C(2)H(4)) is an air stable, yellow solid. X-Ray
      crystallographic data of [N{(C(3)F(7))C(Dipp)N}(2)]Cu(C(2)H(4)) show that the
      1,3,5-triazapentadienyl ligand coordinates to copper in kappa(2)-fashion. The
      copper atom adopts a trigonal-planar geometry.
      [N{(C(3)F(7))C(Dipp)N}(2)]Cu(C(2)H(4)) and [N{(C(3)F(7))C(Dipp)N}(2)]Cu(NCCH(3))
      effectively catalyze carbene and nitrene transfer to a variety of substrates in
      high efficiencies.

PMID- 19759937
TI  - Syntheses, structures and photophysical properties of tetranuclear Cd-Ln
      coordination complexes.
AB  - Four novel hetero-tetranuclear d-f coordination complexes, [Ln2Cd2(p
      toluylate)10(phen)2] (Nd, 1; Pr, 2; Sm, 3) and [Ho2Cd2(p-chloro
      benzoate)10(phen)2](4) (phen = 1, 10-phenanthroline), are synthesized by the
      hydrothermal method, and their structures are studied by single-crystal X-ray
      diffraction. Structures 1-3 are isomorphous and structure 4 has a similar
      molecular structure. In the near-infrared (NIR) region or in the visible region,
      complexes 1-4 show the characteristic emission bands of Ln(III) ions, which are
      attributed to the sensitization from the ligands and d-block (cadmium-ligand
      section) to f-block (lanthanide-ligand section). Moreover, in the Cd-Ln
      complexes, the CdLn separation is very close, so the d-orbital of the Cd(II) ion
      and the f-orbital of the Ln(III) ion may influence each other, which probably
      cause the intra-levels to be adjusted. This can have a significant effect on the
      emission bands in the NIR region, hence the corresponding emission bands of
      complexes 1, 2 and 4 exhibit shift or splitting compared with isolated Ln(III)
      ions. At the same time in the UV-Vis-NIR absorption spectra of the complexes, the
      corresponding absorption bands also show shift or splitting. The shift or
      splitting of bands in the NIR emission spectra and in the absorption spectra can
      evidence each other.

PMID- 19759938
TI  - Ferromagnetic coupled mu-phenoxo-mu-carboxylato heterodinuclear complexes based
      on the Cr(salen) moiety: structural and magnetic characterization.
AB  - The synthesis, crystal structure, and magneto-chemical characterization of two
      new unprecedented -phenoxo--carboxylato heterodinuclear complexes based on the
      Cr(salen) moiety (salen = N,N-bis(salicylidene)ethylenediamine),
      [MII(O2C(CH3)3)(OH2)2(mu-O2C(CH3)3)(-salen)CrIII(O2C(CH3)3)], M = Ni (2), Co(3)
      are reported. The dinuclear complexes were obtained starting from the mononuclear
      trans-[Cr(salen)(CN)2]PPh4 (1), whose crystal structure is also reported. They
      show a trans arrangement of the Cr(salen) unit, bridging through the phenolate O
      atoms to a second metal center. An additional 2-O2-carboxylato bridge and a
      further monodentating carboxylate ligand complete the roughly octahedral Cr(III)
      coordination sphere. The highly distorted octahedral M(II) coordination
      environment is completed by two coordinated water molecules and an additional
      monodentating carboxylate. Variable-temperature solid-state DC magnetization
      studies were carried out in the 2.0-300 K range. Ferromagnetic isotropic pairwise
      exchange parameters were found with values of J = 4.1 cm-1 (2) and J = 2.1 cm-1
      (3). Additionally, for complex 3, a ZFS parameter, D, was employed to properly
      fit the experimental data. Magnetization (M) vs. field (H) and temperature (T)
      data further support the presence of this anisotropic component and confirm
      ground states S = 5/2 and S = 3 for 2 and 3, respectively. Broken symmetry DFT
      calculations properly reproduce the experimental J values supporting the
      ferromagnetic exchange interaction experimentally observed. No out of phase
      susceptibility signal was observed in 0 DC magnetic field for both complexes.
      However, in the case of complex 3 a non-zero is observed when a small external
      field is applied below 3 K, suggesting slow relaxation of the magnetization which
      at 0 DC field is suppressed, probably due to efficient tunnelling relaxation
      pathways. The low symmetry of the Co(II) site in complex 3 may lead to the
      presence of transversal anisotropic components which could be responsible for the
      enhanced tunnelling pathway.

PMID- 19759939
TI  - Activation of ethylene and ammonia at iridium: C-H versus N-H oxidative addition.
AB  - The ammine complexes cis-trans-[Ir(4-C5NF4)(H)2(NH3)(PiPr3)2] (3) and cis-[Ir(4
      C5NF4)(H){(E)-(MeO2C)CCH(CO2Me)}(NH3)2(PiPr3)] (5) are generated on reaction of
      cis-trans-[Ir(4-C5NF4)(H)2(PiPr3)2] (1) or of the vinyl compound trans-[Ir(4
      C5NF4)(H){(E)-(MeO2C)CCH(CO2Me)}(PiPr3)2] (4) with NH3, respectively. Photolysis
      of 5 gives complex [Ir(4-C5NF4)(H){kappa2-(C,O)-(Z)
      (MeO2C)CCH(COOMe)}(NH3)(PiPr3)] (6). Treatment of the ethylene compound trans
      [Ir(4-C5NF4)(C2H4)(PiPr3)2] (2) with ammonia yields C-H activation products such
      as the hydrido vinyl species trans-[Ir(4-C5NF4)(H)(C2H3)(NH3)(PiPr3)2] (7) and
      the cyclometallation products [Ir(4-C5NF4)(H)(NH3){kappa2-(P,C)
      CH2CH(CH3)PiPr2}(PiPr3)] (8a, 8b). A subsequent reaction leads to the generation
      of the binuclear oxidative addition product of ammonia [Ir(4-C5NF4)(H)(
      NH2)(NH3)(PiPr3)]2 (9).

PMID- 19759940
TI  - Steric, geometrical and solvent effects on redox potentials in salen-type
      copper(II) complexes.
AB  - Two diastereomers of the Schiff base ligand [N,N'-bis(2'
      hydroxyphenyl)phenylmethylidene]-1,2-diamino-1,2-diphenylethane (H(2)L) were used
      for the analyses of the redox behaviour of the copper(ii) complexes
      [Cu(L(R,R/S,S))] (rac-) and [Cu(L(R,S))] (meso-). Both complexes were
      structurally characterised by X-ray crystallographic studies and showed square
      planar geometries. The reduction potential of Cu(II) to Cu(I) for meso- was
      higher than that for rac-. This is due to the steric effect of the phenyl
      substituents and the geometrical change in the copper(i) state, which is
      supported by DFT calculations. A red shift of the absorption spectrum was
      observed for meso- in the visible region by the change of solvent from
      dichloromethane to pyridine, while rac- did not show a significant change. The
      effect of solvent on the reduction potential was found to be relatively small.
      The geometrical effect is more important for understanding the electrochemical
      behaviour in this system.

PMID- 19759941
TI  - Reaction of isocyanides with a molybdenum complex containing a tridentate silyl
      phosphine ligand: the Si ligand effect on site preference of the isocyanide
      ligands.
AB  - A molybdenum trihydride complex containing a tridentate silyl-phosphine ligand
      reacts with isocyanides to give isocyanide complexes, in which the Si atom and
      the isocyanides are cis to each other; the preferred configuration in the
      resulting complexes is reasonably explicable provided the Si fragment is acting
      as a good pi-acid ligand.

PMID- 19759942
TI  - One, two and three-dimensional organometallic networks constructed from silver(i)
      pyridyldiethynide complexes.
AB  - Two diethynylpyridines with different geometries were utilized to synthesize
      silver pyridyldiethynide complexes in order to investigate the relation between
      the structure of the coordination network and the geometry of the ligand as well
      as counter anion. Reactions of 2,5-diethynylpyridine with CF3CO2Ag and AgNO3
      afforded [Ag2(2,5-C2PyC2).4CF3CO2Ag] (1) and [Ag2(2,5-C2PyC2).3AgNO3] (2),
      respectively, and a reaction of 2,6-diethynylpyridine with CF3CO2Ag gave [Ag2(2,6
      C2PyC2)3CF3CO2Ag] (3). X-Ray crystallographic studies revealed that in 1, 2,5
      pyridyldiethynide groups as linkers connect silver chains to form a 2D
      organo.etallic network, and are further bridged by CF3CO2- anions to generate a
      3D network, but in 2, 2,5-pyridyldiethynide groups link novel 2D silver layers to
      afford a 3D organometallic network. In 3, 2,6-pyridyldiethynide groups connect
      Ag10 units to generate an organometallic chain as bridging ligands, which are
      further linked by CF3CO2- ligands to form a 2D network. It is demonstrated that
      both the geometry of the ligand and coexisting anions are important factors that
      influence the structures of coordination networks based on silver
      pyridyldiethynide complexes.

PMID- 19759943
TI  - A chemical preformulation study of a host-guest complex of cucurbit[7]uril and a
      multinuclear platinum agent for enhanced anticancer drug delivery.
AB  - Single crystal and powder X-ray diffraction have been used to examine the host
      guest complex of cucurbit[7]uril (CB[7]) and the model dinuclear platinum
      anticancer complex trans-[{PtCl(NH(3))(2)}(2)mu-dpzm](2+) (di-Pt, dpzm= 4,4'
      dipyrazolylmethane). The single crystal structure shows that the host-guest
      complex forms with the di-Pt dpzm ligand within the CB[7] cavity and with the
      platinum groups just beyond the macrocycle portals. Binding is stabilised through
      hydrophobic interactions and six hydrogen bonds between the platinum ammine
      ligands and the dpzm pyrazole amine to the CB[7] carbonyls. Each host-guest
      complex crystallises with two chloride counterions and 5.5 water molecules. The
      unit cell comprises four asymmetric units, each of which contains three
      crystallographically independent CB[7]-di-Pt moieties. X-Ray powder diffraction
      demonstrated structural consistency of the bulk crystals with a single
      polycrystalline phase that is identical with the single crystal structure.
      Finally, the effect of CB[7] encapsulation of the thermal stability of di-Pt was
      examined by thermogravimetric analysis (TGA) and differential scanning
      calorimetry (DSC). From the TGA experiments it was found that free CB[7] and the
      CB[7]-di-Pt complex lose 11 and 3.5% of their mass respectively, through the loss
      of water molecules, upon heating to 160 degrees C. The DSC results showed that
      the free dpzm ligand melts between 186 and 199 degrees C, with a standard
      enthalpy of fusion of 27.92 kJ mol(-1). As a 2+ inorganic salt the metal complex
      does not melt but undergoes several decomposition events between 140 and 290
      degrees C. Encapsulation by CB[7] completely stabilises di-Pt with no
      decomposition of either the macrocycle or metal complex at temperatures up to 290
      degrees C.

PMID- 19759944
TI  - Synthesis and solid-state characterization of platinum complexes with hexadentate
      amino- and iminophosphine ligands.
AB  - Hexadentate ligands cis,cis-C(6)H(9)(N[double bond, length as m
      dash]CHC(6)H(4)(PPh(2)))(3) () and cis,cis-C(6)H(9)(NHCH(2)C(6)H(4)(PPh(2)))(3)
      () were synthesized starting from cis,cis-1,3,5-triaminocyclohexane, and
      characterized using NMR spectroscopy and single-crystal X-ray diffraction. These
      ligands can bind both Pt(0) and Pt(II) metal centers using either or both of the
      soft phosphine moieties and the hard amine/imine moieties. In many cases the
      resulting complexes are negligibly soluble; hence, (31)P and (195)Pt solid-state
      NMR (SSNMR) spectroscopy was applied to analyse the bonding modes of the
      hexadentate ligands. The (195)Pt SSNMR spectroscopy of these complexes is
      particularly challenging, since (1)H-(195)Pt cross polarization is extremely
      inefficient, the (195)Pt longitudinal relaxation times are extremely long and the
      (195)Pt powder patterns are expected to be quite broad due to platinum chemical
      shift anisotropy. It is demonstrated that the ultra-wideline (195)Pt SSNMR
      spectra can be efficiently acquired with a combination of frequency-stepped
      piecewise acquisitions and cross-polarization/Carr-Purcell Meiboom-Gill (CP/CPMG)
      NMR experiments. The (195)Pt and (31)P SSNMR data are correlated to important
      structural features in both Pt(0) and Pt(II) species.

PMID- 19759945
TI  - Spectroscopic characterisation of weak interactions in acidic titanyl sulfate
      iron(II) sulfate solutions.
AB  - The titanyl equilibria in strongly acidic solutions related to the
      hydrometallurgical production of titania have been investigated in the presence
      of inorganic ions (ClO(4)(-), NO(3)(-), Cl(-), SO(4)(2-), Fe(2+) and Fe(3+))
      using spectroscopic (UV-Vis and EPR) methods. UV-Vis experiments showed no
      interaction or ion pairing effect in the acidic titanyl nitrate and titanyl
      perchlorate samples indicating that they would be suitable background
      electrolytes for further thermodynamic measurements. The stoichiometry of the
      titanyl chloride complex was determined as TiOCl(2)(0) and its stability constant
      was calculated (log beta(2) = 1.12 +/- 0.03). The interaction between titanyl and
      sulfate ions was quantified by determining the stoichiometry (1:1) and stability
      (log beta(1) = 1.64 +/- 0.06) of the titanyl sulfate species. Weak sulfate
      complexes were also detected with the ferric (log beta(1) = 2.00 +/- 0.10; log
      beta(2) = 2.49 +/- 0.08) and ferrous (log beta(1) = 1.52 +/- 0.06) ions under
      strongly acidic conditions. A double sulfato complex FeTiO(SO(4))(3)(2-) with
      relatively high stability (log beta = 7.13 +/- 0.07) was found in solutions
      containing titanyl, ferrous and sulfate ions in sulfuric acid medium. In
      addition, an EPR signal was assigned to the FeTiO(SO(4))(3)(2-) species. This
      double sulfato complex was found to be the major metal-containing species in the
      system similar to that used in the leaching process of ilmenite during the
      industrial production of titania.

PMID- 19759946
TI  - Synthesis and photophysics of 4'-R-2,2';6',2''-terpyridyl (R = Cl, CN,
      N(CH(3))(2)) platinum(II) phenylacetylide complexes.
AB  - Platinum terpyridyl (tpy) phenylacetylide complexes with -Cl, -CN, and -NMe(2)
      substituents on the 4'-position of the tpy ligand were synthesized and
      characterized. Their photophysical properties were systematically investigated.
      In addition, theoretical electronic structure calculations using density
      functional theory (DFT) and time-dependent (TD-DFT) approaches were carried out
      for complexes and ; the results of these calculations provided additional
      information on the nature of the electronic structures of the low-lying
      electronic states of these complexes, including the electron density distribution
      and the composition of the frontier molecular orbitals. Complexes exhibit
      moderately intense charge-transfer bands in the visible region, which are
      assigned to the (1)MLCT/(1)LLCT transitions. In comparison to their corresponding
      chloride complexes , these charge-transfer bands become broadened and red
      shifted. Complexes emit at room temperature in CH(3)CN and CH(2)Cl(2) solutions
      and at 77 K in butyronitrile glassy solutions. At room temperature, the emission
      is tentatively attributed to (3)MLCT for and , and to a mixture of
      (3)MLCT/(3)ILCT/(3)pi,pi* for . Due to the admixture of (3)ILCT/(3)pi,pi*
      characters in its emitting state, displays a much higher emission quantum yield
      and longer emission lifetime compared to and . Replacing the chloride co-ligand
      in by phenylacetylide co-ligand clearly enhances the emission and prolongs the
      lifetime. exhibit a broad and moderately intense triplet excited-state absorption
      in the visible to the NIR region, with large excited-state absorption
      coefficients and moderately high triplet excited state quantum yields. Therefore,
      complexes , especially , have potential applications in organic light emitting
      devices (OLED) and as reverse saturable absorbing materials.

PMID- 19759947
TI  - Uranyl-Se(IV) interaction in aqueous acid solutions studied by time-resolved
      laser-induced fluorescence spectroscopy (TRLFS) and UV-Vis spectrophotometry.
AB  - The uranyl-selenium(IV) interaction was studied by time-resolved laser-induced
      fluorescence spectroscopy in aqueous perchloric acid solutions containing 1 x 10(
      4) M U(VI) and Se(IV) at different concentrations (from 0 up to 0.3 M) at pH 1
      and 2. The quenching of uranyl fluorescence is observed. HSeO(3)(-) is
      demonstrated to be responsible for the fluorescence quenching. Stern-Volmer
      analysis gives the dynamic quenching rate constant value (k(q)) (5.0 +/- 0.4) x
      10(9) L M(-1) s(-1) at ionic strength (mu) 0.05 M. The bimolecular excited-state
      process is shown to be diffusion-controlled as k(q) is practically identical to
      the diffusion rate constant as calculated for uranyl and hydroselenite charged
      species. With an increase of HSeO(3)(-) concentration, static quenching occurs in
      addition to the dynamic quenching. The hypothesis of the formation of a weak
      fluorescent ground state complex between uranyl and HSeO(3)(-) is supported. The
      logarithm of the stability constant value (beta) is found to be 3.35 +/- 0.12
      (mu= 0.05 M) and 3.32 +/- 0.15 (mu = 0.2 M). These constants are confirmed by UV
      Vis spectrophotometry. The modelling factor analysis of absorption spectra gives
      logbeta = 3.35 +/- 0.17 (mu = 0.035 M). Extrapolation to mu = 0 by the specific
      ion interaction theory (SIT) gives logbeta degrees = 3.62 +/- 0.15 at 20 degrees
      C.

PMID- 19759948
TI  - Imidazole-based phosphane gold(I) complexes as potential agents for cancer
      treatment: synthesis, structural studies and antitumour activity.
AB  - The reaction of the imidazolyl-4(5)-phosphane ligands 2-isopropylimidazol-4(5)yl
      diphenylphosphane (4-MIP(iPr)) and tris(2-isopropylimidazol-4(5)yl)phosphane (4
      TIP(iPr)) towards gold(I) has been explored and compared to those of analogous 1
      methylimidazol-2-ylphosphane ligands. The structure of [(4-MIP(iPr))AuCl] ()
      shows a linear P-Au-Cl coordination, whereas the 4-TIP(iPr) ligand forms a
      dinuclear complex [{(4-TIP(iPr))Au}(2)]Cl(2) (). Here, 4-TIP(iPr) bridges two
      gold(I) atoms in a head-to-tail P,N fashion. Complex forms in the presence of the
      hard Lewis acid ZnCl(2) the bimetallic complex [AuCl(4-TIP(iPr))ZnCl]Cl (), in
      which 4-TIP(iPr) bridges the two metal centers. In accordance with the HSAB
      concept the Au(I) atom is coordinated by the P atom and the zinc(II) by three N
      atoms in a N,N,N fashion. The solid-state structures of the complexes have been
      elucidated by single-crystal X-ray analysis. The Au(I)-Au(I) contact in is
      2.8821(15) A. The biological activities of all imidazol-2-yl- and imidazol-4(5)
      ylphosphane gold(I) complexes towards nine human cancer cell lines including
      seven ovarian cancer cell lines of different sensitivity towards cisplatin and
      two leukemia cell lines have been explored.

PMID- 19759949
TI  - Water-soluble metal nanoparticles with PEG-tagged 15-membered azamacrocycles as
      stabilizers.
AB  - The synthesis of palladium, platinum and ruthenium nanoparticles stabilized by
      azamacrocycles bearing polyoxyethylenated chains has been achieved by
      decomposition of the corresponding organometallic precursors (Pd(dba)(2),
      Pt(2)(dba)(3) and Ru(COD)(COT)) under dihydrogen atmosphere, whereas gold and
      rhodium nanoparticles have been obtained in the presence of these ligands by
      reduction of HAuCl(4) and RhCl(3), respectively. The metal nanoparticles were
      characterized by several techniques including IR, NMR, UV-vis, HRTEM, ED, and
      elemental analysis. The Pd nanoparticles have been used as recoverable catalyst
      in Suzuki cross-coupling in aqueous medium.

PMID- 19759950
TI  - Structural and magnetic variability of cobalt(II) complexes with bridging
      pyrazolate ligands bearing appended imine groups.
AB  - The synthesis of new binucleating pyrazole-derived ligands (HL2, HL3) with bulky
      2,6-diisopropylphenylimine side arms and backbone phenyl groups at the pyrazole
      C4 and/or at the imine-C, which are derivatives from the known ligand HL1, is
      reported. Crystallographic analyses of three cobalt(II) complexes coordinated by
      ligands [L1-3]- reveal distinct metal to ligand ratios and different structural
      motifs in the solid state: [L1Co2Cl3(H2O)2(EtOH)] (1), [(L2)3Co4Cl5] (2), or
      [(L3)2Co4Cl6(H2O)5] (3). Metal ions are five-coordinate in 1, four- and six
      coordiante in 2, and six-coordinate in 3. UV-Vis spectroscopy and ESI mass
      spectrometry suggest that complexes 2 and 3 retain their structures also in
      solution, whereas 1 partially dimerizes and is in equilibrium with tetrametallic
      species akin to 3. Magnetic susceptibility measurements indicate weak to moderate
      antiferromagnetic coupling between five-coordinate or between six-coordinate
      cobalt(II) ions, but weak ferromagnetic coupling between four- and six-coordinate
      cobalt(II).

PMID- 19759951
TI  - Unique two-fold interpenetration of 3D microporous 3d-4f heterometal-organic
      frameworks (HMOF) based on a rigid ligand.
AB  - Six heterometal-organic frameworks, {[LnCu1.5(BPDC)3(H2O)2].mH2O}n (Ln = Gd (1, m
      = 4.75), Tb (2, m = 3.75), Eu (3, m = 5), Ho (4, m = 2), Yb (5, m = 2.25), BPDC =
      4,4-dicarboxylate-2,2-dipyridine anion), and {[LuCu1.5(BPDC)3(H2O)1.5].2.5H2O}n
      (6), have been synthesized under hydrothermal conditions. The structure analyses
      for 1-6 reveal that the six compounds are isomorphous, belonging to the
      monoclinic system with space group C2/c, and display two-fold interpenetrating 3D
      frameworks, which are the first examples of d-f heterometal-organic frameworks
      based on a rigid ligand. These frameworks were further characterized by elemental
      analyses, TG analysis, PXRD, hydrogen adsorption and variable-temperature
      magnetic susceptibilities. Interestingly, hydrogen adsorption was significantly
      observed under the existence of the two-fold interpenetration. Magnetic
      investigations suggest that the ferromagnetic coupling exists between Gd3+ and
      Cu2+ in 1, and that the nature of the interaction between Ln3+ and Cu2+ ions in
      compounds 2, and 4-6 cannot be absolutely determined when MT values are reduced
      with decreasing temperature.

PMID- 19759952
TI  - Iron(II)-octacyanoniobate(IV) ferromagnet with T(C) 43 K.
AB  - We have synthesized the octacyanoniobate-based cyano-bridged 3D ferromagnet
      {[Fe(II)(H(2)O)(2)](2)[Nb(IV)(CN)(8)].4H(2)O}(n) and characterized structurally,
      spectroscopically (XANES/EXAFS, IR, UV-Vis, Resonance Raman, (57)Fe Mossbauer
      spectroscopy) and magnetically. crystallizes in the tetragonal system, space
      group I4/m, a = 11.989(5) A, c = 13.237(5) A, V = 1902.6(13) A(3). 3D
      coordination architecture comprises two types of Nb(IV)-C-N-Fe(II)(HS) (HS = high
      spin) linkages with Fe-N-C angles of 154.5 degrees and 167.5 degrees . The
      XANES/EXAFS spectra at Fe:K and Nb:K lines confirm the presence of Nb(IV)-C-N
      Fe(II) linkages. Magnetic measurements reveal ferromagnetic ordering below T(c) =
      43 K with some non-collinearity of Nb(IV) (S = 1/2) and Fe(II) (S = 2) magnetic
      moments. The molecular field model simulation reproduces well the M(T) curve and
      T(c) value with one average exchange coupling constant J(FeNb) = + 8.1 cm(-1).

PMID- 19759953
TI  - Effect of metal exchange (Os vs. Ru) and co-ligand variation (Cl(-)vs. acac(-))
      on the oxidation state distribution in complexes of an o-phenylenediamido(2(-))/o
      quinonediimine redox system.
AB  - The compounds OsCl2L2 (1), RuCl2L2 (2) and Ru(acac)2L (3), Ldegrees = N-phenyl-o
      quinonediimine and acac- = 2,4-pentanedionato, have been synthesised and
      electrochemically, spectroscopically and structurally characterised with the
      support of detailed DFT calculations. For the new osmium compound 1, the average
      values for CNH (1.331 A), CNPh (1.345 A) and CC(meta) bond lengths at 1.360 A
      agree more with an o-semiquinonediimine than with an o-quinonediimine formulation
      for the coordinated ligand, whereas the latter assignment is more appropriate to
      describe the ruthenium analogue 2 (average bond lengths of 1.308, 1.324 and 1.348
      A, respectively). In turn, the corresponding average bond lengths in 3 (1.333,
      1.352 and 1.350 A, respectively) are suggestive of an o-semiquinonediimine
      ligand. DFT calculations confirm the structural data and describe the electronic
      structures related to the oxidation state assignments. The stabilisation of
      trivalent ruthenium by electron donating acac- in 3 = RuIII(acac)2(L*-) and the
      preference of osmium for higher oxidation states (here: OsIVCl2(L*-)2 in 1) as
      compared to ruthenium analogues (here: RuIICl2(Ldegrees)2 in 2) in otherwise
      similar setting is responsible for these results. Oxidation of the diamagnetic
      complexes proceeds to partly EPR and UV-VIS spectroelectrochemically detectable
      cations with metal-centered spin, suggesting the following formulations:
      [OsIIICl2(Ldegrees)2]+ for 1+, [RuIIICl2(Ldegrees)2]+ for labile 2+, and
      [RuIII(acac)2(Ldegrees)]+ for 3+. In the case of 3, reversible metal-centered
      reduction results in ligand-based spin as compatible with a [RuII(acac)2(L*-)]-
      situation for 3-.

PMID- 19759954
TI  - Hard/soft selectivity in ligand substitution reactions of beta-diketonate
      platinum(II) complexes.
AB  - The reactivity of platinum(II) complexes of the type [PtCl(O,O-acac)(L)] (1) and
      [Pt(O,O-acac)(gamma-acac)(L)] (2) (L = DMSO, a; DMS, b), with a range of hard and
      soft nucleophiles such as dimethylsulfide (DMS, b), triphenylphosphine, (PPh3,
      c), ethylene (eta2-C2H4, d), carbon monoxide (CO, e), pyridine (py, f), and
      guanosine (Guo, g) has been investigated. Interestingly, the complexes 1a and 1b
      undergo selective substitution of the chloro or sulfur ligand depending on the
      hard/soft character of the incoming nucleophile. The soft incoming ligand
      replaces the softer one and the hard ligand replaces the harder one, giving
      [PtCl(O,O'-acac)(L)] complexes (1b, 1c, 1d and 1e in the reaction of 1a with L =
      DMS, PPh3, eta2-C2H4, CO, respectively), and [Pt(O,O'-acac)(DMSO)(L')] (3f, 3g)
      and [Pt(O,O'-acac)(DMS)(L')] (4f, 4g) species in the reaction of 1a and 1b with
      L' = py and guo, respectively. In the cases of 2a and 2b complexes, where the pi
      bonded acac (gamma-acac) replaces the chloro ligand, only in the presence of an
      incoming soft nucleophile substituting the soft sulfur ligand the reaction
      occurs. Equilibrium constants for the substitution reactions were measured by 1H
      NMR spectroscopy. Variable temperature 1H NMR spectroscopy studies, performed for
      the reaction of 1a and 2a complexes with DMS, revealed that the selective
      substitution of DMSO with DMS takes place in both cases, according to a second
      order kinetic law. The calculated values of DeltaH++ and DeltaS++ are consistent
      with an associative mechanism. NMR spectroscopic characterization (1H, 13C,
      195Pt, 31P) for the complexes and crystal structures of isolated complexes
      ([PtCl(O,O'-acac)(L)] (1) and [Pt(O,O'-acac)(gamma-acac)(L)] (2), L = DMSO, 1a
      and 2a; L = DMS, 1b and 2b; L = PPh3, 1c and 2c) are herein reported and
      discussed.

PMID- 19759955
TI  - Chiral triaryl phosphite-based palladacycles and platinacycles: synthesis and
      application to asymmetric Lewis acid catalysis.
AB  - The optically pure monophosphites P(OAr)(BINOLate) (7, where Ar = 2,4-di-tert
      butylphenyl) have been prepared by treatment of PCl2(OAr) with R- or S-BINOL.
      Treatment of [PdCl2(NCMe)2] with 7 gave [PdCl2(7)2] (9) or the binuclear
      orthometallated complex [Pd2Cl2(7-H)2] (8) depending on the reaction conditions.
      Bridge cleavage reactions of 8 gave [PdCl(7-H)(L)] with L trans to carbon when L
      = PPh3 or 7 and cis to carbon when L = N-heterocyclic carbene. Treatment of
      [PtCl2(NCtBu)2] with 7 gave [PtCl2(7)2] (18) which upon further reaction with
      PtCl2 furnished a mixture of binuclear [Pt2Cl2(7-H)2] (17) and cis-[PtCl(7-H)(7)]
      (19). The palladium complexes containing cyclometallated 7 were screened for
      catalysis of 1,4-conjugate addition of phenylboronic acid to cyclohexen-2-one and
      the allylation of benzaldehyde with allyltributyltin. Conversions were generally
      high in each case but enantioselectivities were low (15% e.e. at best). The X-ray
      crystal structures of 8, 17 and [PdCl(7-H)(NHC)] (10a, where NHC = 1,3
      (dimesityl)imidazolidin-2-ylidene) have been determined.

PMID- 19759956
TI  - New photomagnetic cyanido-bridged Cu(II)-Mo(IV) oligonuclear complexes: slight
      modification of the blocking ligands induces different structures.
AB  - A pentanuclear complex, [Mo(CN)8{CuL1}2{CuL1(H2O)}2].6H2O 1, and a decanuclear
      one, [Mo(CN)8{CuL2}3{CuL2(H2O)}]2.10H2O 2, have been obtained following the
      building-block approach (HL1 and HL2 are tridentate Schiff bases obtained by
      reacting salicylaldehyde with 2-aminomethyl-pyridine and 2-aminoethyl-pyridine,
      respectively). Both compounds present reversible photo-induced magnetic
      properties interpreted as a MoIV-CuII charge transfer. Compound 2 exhibits a
      lower efficiency of this metal-metal charge transfer than compound 1 attributed
      to a less flexible structure of 2 compared to 1.

PMID- 19759957
TI  - Preparation and properties of cyclic and open-chain Sb/N-donor ligands.
AB  - The preparations of both open-chain and cyclic mixed-donor Sb/N ligands, MeN(CH2
      2-C6H4)2SbMe (1), MeN(CH2-2-C6H4SbMe2)2 (2), CH2{CH2N(Me)CH2-2-C6H4SbMe2}2 (3)
      and CH2{CH2N(Me)CH2-2-C6H4}2SbMe (4), are described via reaction of
      chlorostibines with dilithio-reagents, and their spectroscopic properties
      established. Air-stable stibonium derivatives of (3) and (4) have been isolated
      by treatment of the compounds with excess MeI, which leads to quaternisation at
      the Sb atoms exclusively. A crystal structure of a bis(stibonium) derivative of
      (3), [CH2{CH2N(Me)CH2-2-C6H4SbMe3}2]I2, reveals hypervalency at Sb through long
      range Sb...N interactions (ca. 2.87 A), giving pseudo-five-membered rings fused
      to the aromatic rings, and distorted trigonal bipyramidal coordination at Sb. The
      coordinating properties of compounds (1) to (4) have been investigated through
      their reactions with Cu(I), Mn(I), Mo(0) and Pt(IV) reagents, and for (1) and (4)
      by reaction with Fe(0), giving [Fe(CO)4(L)]. The spectroscopic data (IR, 1H,
      13C{1H}, 55Mn, 63Cu, 95Mo and 195Pt NMR), mass spectrometry and microanalyses for
      this series of complexes confirm that coordination occurs via the Sb donor atoms
      in all cases, with N-coordination only present in fac-[Mn(CO)3(2)](CF3SO3).
      Crystal structures of [Cu(2)2]BF4, [Mo(CO)4(2)] and [PtMe3I(2)] confirm the
      coordination modes, showing (2) functioning as a wide-angle bidentate distibine.
      The structures also show the amine N-donor atoms in the complexes are involved in
      a hypervalent SbN interaction (ca. 3.0 A) with one of the coordinated Sb atoms in
      each ligand, leading to significant differences in the conformations of the
      carbon backbones linking the Sb and N atoms. Reaction of Na3[RhCl6].12H2O with
      one mol equiv. of (2), (3) or (4) leads to the bis-ligand complex [RhCl2(2)2]Cl
      and the 1 : 1 Rh : L complexes [RhCl2(3)]Cl and [RhCl3(4)], both of which involve
      coordination via the Sb and N donor atoms.

PMID- 19759958
TI  - Synthesis and structures of beta-dialdiminatoantimony(III) halides and beta
      dialdiminium hexahalogenoantimoniates.
AB  - From SbCl3, SbBr3 or SbI3 and an equivalent portion of the -dialdiminatopotassium
      compound K[{N(C6H3Pri2-2,6)C(H)}2CPh] [[triple bond]K(L)] in Et2O there was
      obtained in good yield the crystalline yellow [SbCl2(L)].(0.5thf).(0.5Et2O) (1)
      and the bis(bromo) analogue 2, or the orange [{SbI(L)(mu-I)}2].(0.5Et2O) (3).
      Each of 1-3 was treated with the appropriate dihalogen (X2) in Et2O. Thus,
      whereas 1 or 2 furnished the corresponding -dialdiminium hexahalogenoantimoniate
      [Et2O...H(L)H...OEt2][SbX6] (4, X = Cl; 6, X = Br), the iodo compound 3 afforded
      the known pyrazolium salt [N(C6H3Pri2-2,6)C(H)C(Ph)C(H)N(C6H3Pri2-2,6)][I5]. It
      is suggested that the source of the additional 2HX, required to convert 1 or 2
      with X2 in Et2O into 4 or 6, was derived from halogenation of the N-aryl groups
      of L. The formation of 4 or 6 was achieved by the alternative synthesis from
      equivalent portions of [H2(L)]X, SbX3 and X2 in diethyl ether. The X-ray
      structures of the isomorphous compounds 1 and 2 and 4 and 6, as well as of 3, are
      reported.

PMID- 19759960
TI  - Academic bridge to the community: the ABCs of a service-learning model.
AB  - The purpose of this report is to outline the process, obstacles, and outcomes for
      the development and successful implementation of a service-learning experience
      between the Department of Physical Therapy at the University of Texas
      Southwestern Medical Center and the Muscular Dystrophy Association of Dallas. The
      rationale for initiation of the partnership is outlined, and curriculum planning
      concerns and integration are presented. These include development of community
      partnerships, identification of curricular placement, and development of academic
      and community roles, including didactic and clinical objectives for the
      participants. The importance of understanding the service-learning philosophy and
      evaluation of the student and community impact is emphasized. Outcomes report
      students' assessments encompassing issues of both prior and future didactic
      education, development of clinical skills and problem solving, and evaluation of
      professional and personal issues. It is suggested that this model of service
      learning project has the ability to be implemented across a wide spectrum of
      allied health care curricula.

PMID- 19759961
TI  - The impact of education and experience on physician assistant students'
      perception of cultural awareness, knowledge and skills.
AB  - A tool to measure health care students' perception of their cultural awareness,
      knowledge and skills was developed and its reliability tested on a group of
      Physician Assistant (PA) students. The tool was then used to evaluate perceptions
      of cultural awareness, knowledge, and skills in two groups of students before and
      after their education for their physician assistant bachelor's degree. One group
      received a basic introduction to cultural issues. The other group was exposed to
      multiple classroom discussions of cultural concerns as well as being required to
      participate in experiences that provided cross-cultural interaction. Results
      indicated a significant increase in perceived cultural knowledge and skills for
      the group that was involved in cross cultural experiences as well as expanded
      instruction about other cultures.

PMID- 19759962
TI  - Nutrition knowledge and attitudes of allied health and fitness students.
AB  - Using survey methodology, this study assessed the nutrition-related knowledge and
      attitudes of nursing (n = 54), physical therapy (n = 48), and fitness (n = 62)
      students. The mean scores on the nutrition knowledge test were 21 points (SD 3.8
      points, range 8 to 28 points) for nursing, 21 points (SD 3.0 points, range 15 to
      27 points) for physical therapy, and 22 points (SD 3.9 points, range 15 to 31
      points) for fitness students, out of a possible 32 points. Students with previous
      exposure to nutrition education earned significantly (p < .05) higher scores. The
      majority of students planned to comply with, and to encourage client compliance
      with recommendations to decrease fat intakes, maintain a healthy weight, and
      include fruits and vegetables in their daily diet, and generally regarded
      nutrition as important to their chosen profession. Findings suggest a need to
      enhance and reinforce key nutrition principles and to promote a greater
      appreciation for the role of the registered dietitian as a valuable member of the
      health care team. Interactive nutrition education activities throughout the
      health sciences curricula and presentations by registered dietitians describing
      their job responsibilities may help attain these outcomes. In conclusion,
      findings suggest a need to promote increased interdisciplinary collaboration
      among future allied health professionals to provide evidenced base care.

PMID- 19759963
TI  - A preliminary analysis of preparation strategies and other correlates to
      performance on a basic science qualifying exam in chiropractic.
AB  - BACKGROUND: Due to the high-stakes nature of board exams, students who enroll in
      chiropractic and other healthcare educational programs spend a significant amount
      of time and money on preparation strategies including: commercial coaching
      courses, course notes, commercial note sets, old test questions, online
      resources, text books and small group study sessions. However, whether such
      strategies help predict academic performance on the National Board exams has
      received little attention by researchers in chiropractic education. OBJECTIVE:
      The purpose of this study is to evaluate the effects of study strategies, student
      demographics, prepared materials and other measures of general academic
      preparedness on the National Board of Chiropractic Examiners (NBCE) Part I exam
      performance. DESIGN: A Student survey utilizing descriptive statistics was used
      and multivariable analysis was performed. METHODS: Two hundred twenty-nine
      subjects completed a 52-item survey. Participants were asked to describe their
      study preparation for the NBCE Part I exam. Survey responses were then examined
      with composite NBCE Part I scores, selected demographics, pre-chiropractic
      cumulative grade point average (GPA), and in-program chiropractic college GPA.
      RESULTS: Pre-chiropractic GPA and in-program GPA correlated significantly to the
      response variable (NBCE Part I Scores). Using multiple regression, the paired
      variables of past education and in-program GPA accounted for a significant
      portion (R(2) = .638, P < .001) of the total variance in NBCE Part I scores.
      Further, the in-program GPA variable alone accounted for significant unique
      explanation (change R(2) =.368, P < .001). Demographics, employment status,
      preparation strategies, and prepared materials were considerably less potent
      predictors of performance on Part I of the NBCE exam. DISCUSSION/CONCLUSION: This
      study raises questions concerning the effectiveness of preparation strategies
      including commercial coaching courses on the National Board examination scores.
      Further, the results suggest that short-term preparation strategies and study
      efforts immediately before the NBCE Part I exam (as well as other factors) have a
      minimal correlation to exam scores. In this study, pre-chiropractic GPA, in
      program GPA, and post-secondary education completed before matriculation into
      chiropractic college were the best predictors of performance on NBCE Part I.

PMID- 19759964
TI  - A brief note on further investigating correlates of work exhaustion for medical
      technologists.
AB  - Using a sample of 184 medical technologists (MTs) over a three-year period, this
      study found support for the hypothesis that downsizing leads to higher job loss
      insecurity and task load perceptions, which both lead to increased work
      exhaustion. As such this study extends previous research on MT work exhaustion by
      Blau, Tatum and Ward-Cook. Study limitations and future research issues are
      briefly discussed.

PMID- 19759965
TI  - Barriers to school based physical therapy perceptions of physical therapists in a
      rural state.
AB  - The enactment of the Education for All Handicapped Children Act provided children
      with disabilities the right to be educated with their peers in public schools.
      The related services provision of the Act requires public schools to hire
      appropriate personnel, including physical therapists, to enhance educational
      opportunities for children with disabilities. PURPOSE: The purpose of this study
      was to explore perceived barriers to optimal school-based physical therapy
      practice and delivery identified by Idaho school-based therapists. METHODS: Forty
      eight Idaho school-based physical therapists were sent the survey instrument
      developed for this study. Thirty-six Idaho school-based therapists returned the
      survey (response rate 75%). RESULTS: Data analysis substantiated four barriers to
      school-based physical therapy practice: financial constraints, administrative
      issues, personnel shortages, and limited understanding of disability law. A
      statistically significant difference (p < 0.05) was found between participant
      perceptions of barriers within their school and their perceptions of barriers
      statewide. CONCLUSIONS: Overall, participants perceived, to varying degrees, that
      although barriers were present at the school level, state level barriers were
      even greater.

PMID- 19759966
TI  - Managing post-therapy fatigue for cancer survivors using energy conservation
      training.
AB  - This pilot study evaluated the effectiveness of energy conservation training to
      help post-therapy cancer survivors manage their fatigue. Twelve post-therapy
      cancer survivors were randomly assigned to an energy conservation training or
      usual care control (6 in each group). Participants in the intervention group
      received 1 to 2 hours of individual, face-to-face energy conservation training
      from an occupational therapist followed by once-a-week telephone monitoring
      sessions in the subsequent three weeks. Participants in the control group
      received standard care from their oncologist. Analysis of pre- and post-training
      data from the Piper Fatigue Scale (PFS) revealed significant reduction only in
      the sensory subscale of the PFS (Z = 2.21; p = 0.027) for the intervention group;
      but no significant reduction in the four subscale or total scores of the PFS for
      the control group. Findings demonstrate partial support for the effectiveness of
      energy conservation training in helping post-therapy cancer survivors manage
      their fatigue. Energy conservation training seems to be a viable strategy for
      managing cancer-related fatigue, though its efficacy is modest. Incorporating
      specific energy restoration strategies such as relaxation and meditation for
      future research may help advance the growing body of knowledge in symptom
      management for post-therapy cancer survivors.

PMID- 19759967
TI  - Education for caring in a multicultural society - a COHEHRE development:
      perception of cultural awareness, knowledge and skills.

PMID- 19759968
TI  - What is professionalism in the applied health sciences?

PMID- 19759969
TI  - Education for caring in a multicultural society--a COHEHRE development.

PMID- 19759970
TI  - Influence of learning style on instructional multimedia effects on graduate
      student cognitive and psychomotor performance.
AB  - BACKGROUND AND PURPOSE: Learning outcomes may improve in graduate healthcare
      students when attention is given to individual learning styles. Interactive
      multimedia is one tool shown to increase success in meeting the needs of diverse
      learners. The purpose of this study was to examine the effect of learning style
      and type of instruction on physical therapy students' cognitive and psychomotor
      performance. SUBJECTS: Participants were obtained by a sample of convenience with
      students recruited from two physical therapy programs. Twenty-seven students
      volunteered to participate from Program 1. Twenty-three students volunteered to
      participate from Program 2. METHODS: Gregorc learning styles were identified
      through completion of the Gregorc Style Delineator. Students were randomly
      assigned to one of two instructional strategies: 1) instructional CD or 2) live
      demonstration. RESULTS: Differences in cognitive or psychomotor performance
      following instructional multimedia based on learning style were not demonstrated
      in this study. Written examination scores improved with both instructional
      strategies demonstrating no differences between the strategies. Practical
      examination ankle scores were significantly higher in participants receiving CD
      instruction than in participants receiving live presentation. Learning style did
      not significantly affect this improvement. Program 2 performed significantly
      better on written knee and practical knee and ankle examinations. DISCUSSION AND
      CONCLUSION: Learning style had no significant effect on student performance
      following instruction in clinical skills via interactive multimedia. Future
      research may include additional measurement instruments assessing other models of
      learning styles and possible interaction of learning style and instructional
      strategy on students over longer periods of time, such as a semester or an entire
      curriculum.

PMID- 19759971
TI  - Occupational therapy students and emerging practice: a pilot study.

PMID- 19759972
TI  - An interactive electronic instructional unit on substance abuse.
AB  - This paper describes an approach to instruction for allied health students in
      screening and brief intervention to assist children and adolescents living with
      adults who are abusing substances. Substance abuse is a major public health
      problem in the United States; among its outcomes is damage to children living in
      the home. Health professionals should screen child and adolescent clients to
      determine whether adults in the home are substance abusers, and provide help for
      children living with such adults. An interactive electronic instructional unit,
      suitable for either independent study or classroom use, was developed to provide
      this content to allied health students. The unit includes an introductory page,
      followed by pages focused on the scope of the problem, screening, and brief
      intervention. Evaluation by means of a pre and post-test suggested that the unit
      has the potential to increase occupational and physical therapy students'
      knowledge and modify attitudes regarding their role in providing screening,
      referral, and brief intervention for this population.

PMID- 19759973
TI  - How knowledgeable are physician assistants and nurse practitioners about physical
      therapy?
AB  - Non-physician providers (NPPs) are on the front line for referring consumers for
      physical therapy (PT) services. Previous studies have assessed physicians'
      knowledge and utilization of PT. No studies have examined these same issues for
      physician assistants (PAs) or nurse practitioners (NPs). The purpose of this
      study was to determine the current level of PAs' and NPs' knowledge of PT and the
      degree to which their knowledge levels differ. This assessment is important to
      ensure that potential PT patients are referred appropriately for these services.
      A proportional sample of 1000 Arizona NPPs was surveyed. NPP respondents'
      knowledge of PT procedures was relatively low, with a 58.7% mean score. PA
      respondents demonstrated greater knowledge of PT procedures than did NPs. Both
      disciplines should be more intensely exposed to the potential benefits of this
      service for patients.

PMID- 19759974
TI  - Scenes from a virtual Europe.

PMID- 19759975
TI  - Analyzing course objectives: assessing critical thinking in the pharmacy
      curriculum.
AB  - Assessment of critical thinking objectives in a pharmacy program curriculum is an
      important part of program assessment. This study measures the proportion of
      cognitive learning objectives at various levels of Bloom's taxonomy throughout
      the required curriculum using the stated objectives in course syllabi (the
      explicit curriculum). In one entry level doctor of pharmacy program, 54.90% of
      cognitive objectives identified critical thinking outcomes using the rubric of
      Bloom's level 3 or higher as an indicator of critical thinking. In this program,
      there was a similar percent of critical thinking objectives in each of the first
      three years, but the final year of the curriculum had a higher percent of
      critical thinking objectives than each of the first three years (p = 0.0018,
      Kruskal-Wallis test). The increase in critical thinking in the final year
      suggests that the explicit expectations in the syllabi are weighted toward a
      higher percent of critical thinking objectives during clinical rotations. The
      methods described in the study may serve as tools for a curriculum committee or
      program assessment team to compare critical thinking in the curriculum at
      different points in time, and may assist in curricular mapping efforts. These
      methods may complement studies measuring the implicit curriculum (that which the
      faculty actually teach, which may not be stated in the explicit curriculum.).

PMID- 19759976
TI  - A measure of fall risk behaviors and perceptions among community-dwelling older
      adults.
AB  - PURPOSE: Relatively little is known about the interaction between behavioral and
      environmental circumstances associated with falls among community-dwelling older
      adults. This study is designed to develop an instrument that measures community
      dwelling older adults' participation in and perceptions of fall risk behaviors.
      METHOD: Eighty-seven community-dwelling older adults aged 60 or above (mean +/-
      SD = 76 +/- 7.9), who had experienced at least one fall in the past 12 months,
      completed a questionnaire dealing with frequency of their participation in fall
      risk behaviors, their perceptions of these behaviors, and their fall history.
      Data were subjected to exploratory factor analysis. RESULTS: A 20-item instrument
      consisting of three constructs was presented as the Fall Risk Behaviors and
      Perceptions Scale (FRB&PS). Two of the three constructs of the instrument were de
      stabilizers and non-supports, both of which measure participation in fall risk
      behaviors; the third was perceptions of fall risk behaviors. Internal consistency
      coefficient of the FRB&PS is 0.733 with a root mean square error of approximation
      (RMSEA) score of 0.075, which indicates an adequate model fit. Results from the
      stepwise regression analyses indicated that adults aged 75 and above (the old
      old) participated less frequently in fall risk activities (p = 0.025), and had
      more knowledge about fall risks as measured by a higher perception score (p =
      0.025) than those aged 60 to 75 (the young-old). Older men tended to participate
      more frequently in fall risk activities (p = 0.020) than older women; in
      addition, those older adults who are more mobile (p = 0.002) also participated
      more frequently in fall risk behaviors than those who are less mobile.
      CONCLUSION: Preliminary findings indicate that the pilot FRB&PS is a reliable and
      valid instrument to measure community-dwelling older adults' participation in and
      perceptions of fall risk behaviors. Additional psychometric validation of the
      FRB&PS on predicting the likelihood of falls is warranted.

PMID- 19759977
TI  - Evaluation of physical therapists' knowledge, attitudes, and professional use of
      dietary supplements: implications for practice and education.
AB  - PURPOSE: The objective of this cross-sectional study was to better define
      physical therapists' (PTs) knowledge, attitudes, and professional reported use of
      dietary supplements (DSs). METHODS: This study was approved by University of
      Colorado Investigational Review Board. A survey was developed and piloted to
      evaluate knowledge of supplement indications and serious side effects; comfort in
      performing medication and supplement histories and making therapeutic
      recommendations; and current practice and attitudes of supplement use and
      resource information. Therapists were identified through the Colorado Board of
      Physical Therapy. Five hundred surveys were mailed. Analysis of the survey items
      consisted of descriptive statistics and qualitative analysis of free text for
      themes and concepts. RESULTS: One-hundred eighty-four surveys were returned (38%
      response rate). Eighty-two percent were female. Forty-nine percent had a
      baccalaureate degree, 38 % master's degree, and 1.6 % Doctor of Physical Therapy.
      Over 50% practiced in an ambulatory setting. While 46% believed they were
      adequately educated on DS, only 50% of respondents could identify the correct
      indication for the designated supplement, while less than 6% one correct serious
      side effect, once efedra was excluded. For supplement information, more than 90%
      turned to non-peered review materials. Forty percent of therapist indicated that
      they were currently recommending DSs to their patients. Glucosamine, glucosamine
      with chondroitin, and methyl-sulfonylmethane comprised the top supplements
      suggested. CONCLUSIONS: PTs are recommending DS within their practice. While many
      therapists noted they were adequately educated, gaps in knowledge base were
      apparent. As physical therapy curricula continue to evolve, the addition of DS
      instruction should be considered a priority, as well as, steps put in place to
      provide additional education for practicing therapists.

PMID- 19759978
TI  - The personality traits of medical technologists: implications for recruitment and
      retention.
AB  - Clinical laboratory science is in the midst of a perfect storm. The turbulent
      nature of the employment market along with diagnostic pathology's mission to
      develop new, powerful diagnostic tools imply a future that will be both
      challenging and rewarding. Yet, success in the future will require immediate
      attention to current issues of recruitment, retention and expansion of the
      medical technologist's role. An analysis of the personality traits of medical
      technologists may provide insight into work preferences as they relate to job
      satisfaction and willingness to accept the changes in the profession. In this
      study, we will attempt to gain this insight through examination of a personality
      profile of a group of medical technologists.

PMID- 19759979
TI  - Interdisciplinary health science education to promote cultural competence.

PMID- 19759980
TI  - Influence of an information literacy course on students' information search
      behavior.
AB  - The purpose of this study was to determine the influence of an information
      literacy course on students' information gathering behavior. METHODS: Two student
      groups, consisting of 69 (Group One) and 177 (Group Two) students, were compared
      in their performance on a literature review assignment. Group one did not have an
      information literacy course, while group two was the first class to receive a
      newly introduced course in information literacy. Assignment references served as
      the dependent variables and included the following categories: total number of
      references, number and percentage of peer reviewed journal references, number and
      percentage of non-peer reviewed journal references, number and percentage of
      website references, number and percentage of authority opinion references, and
      number and percentage of textbook references. Referenced websites were further
      divided into the following: .com, .org, .edu, .gov. for both total number and
      percent utilization.Independent T-tests were performed between the information
      literacy course status and each of the dependent variables. RESULTS: Descriptive
      data (prior education, cumulative GPA, average age of student groups) was similar
      for both groups. Independent T-test analysis revealed a strong association (p <
      .05) between increasing both the number and percentage of peer reviewed
      references and having the information literacy course. CONCLUSIONS: The
      introduction of an information literacy course did influence the information
      gathering behavior of students. Students showed an increased reliance on peer
      reviewed references.

PMID- 19759981
TI  - Student perceptions of the use of debate as a teaching strategy in the allied
      health professions.
AB  - This paper presents results from a survey regarding student perceptions of the
      use of debate in two occupational therapy courses. The survey was initially used
      as a classroom evaluation, consisting of open-ended questions asked by the
      instructor and answered by students in a research and a policy course. Students
      then were randomly assigned to two groups, which present their arguments and then
      fielded questions. After the debates, students were asked to answer four
      questions: 1) What did I learn from the debate?; 2) What did you like best about
      the debate?; 3) What did you like least about the debate?; and 4) Would you
      recommend this activity for future classes? Results of the student's comments to
      the four questions showed that debate was perceived by the majority of students
      as a useful technique for discussing issues both in a research course and in a
      health policy-related course. Comments from students showed that debate
      encouraged active participation in class, out of class research experiences,
      provided an opportunity to discuss issues and develop conclusions, and promoted
      the ability to advocate for themselves.

PMID- 19759982
TI  - Impact of cultural contact on intercultural competency of occupational therapy
      students and international graduate students.
AB  - This study examined changes in cultural perceptions and communication of 47
      occupational therapy students and 39 international graduate students following 5
      peer teaching activities. The peer-teaching activities were designed on the
      premise that positive contact between people of equal status improves
      intercultural competency, and included social exchanges, interviews, feedback on
      practice teaching, and role-playing. Changes in intercultural competency were
      measured with pre- and post administration of the Cross Cultural Adaptability
      Inventory (CCAI), as well as questionnaires and journals. Significant positive
      change between pre- and post-test scores on the CCAI (p<.0002) was found for the
      86 participants. When stratified into 3 subgroups (international students and
      occupational therapy students with and without international travel experience),
      changes were more pronounced. Occupational therapy students with international
      travel experience benefited the most from the peer-teaching activities (p<.002)
      and international graduate students benefited as well (p<.009). Occupational
      therapy students without international travel experienced no significant change.
      The findings indicate that peer teaching activities significantly impacted cross
      cultural communication for students with prior international travel experience
      and confirm the importance of contextual learning.

PMID- 19759983
TI  - Increasing access to oral health care in underserved areas of Missouri: dental
      hygiene students in AHEC rotations.
AB  - In 2004 personnel from the Missouri Area Health Education Centers and faculty
      from the University of Missouri-Kansas City, School of Dentistry, Division of
      Dental Hygiene, joined forces to develop dental hygiene student rotations to
      rural and underserved areas. Twenty-six students participated in a two week
      rotation to Federally Qualifed Health Centers throughout Missouri. The rotations
      included objectives which focused on student familiarity with 1) the similarities
      and differences between private practice and public health clinics, 2) assessing,
      planning, implementing and evaluating an oral health education program, 3)
      working with a diverse population; and 4) an understanding of the ethics of
      delivering healthcare to a whole community versus individual patients.
      Additionally, the rotation sought to continue to develop the students' clinical
      skills under supervised instruction. The rotation was evaluated using various
      qualitative and quantitative measurements, including journals, task records and
      post-program surveys. This article reports on the results of the qualitative and
      quantitative measures used for evaluating the objectives of the project.

PMID- 19759984
TI  - The community health worker cultural mentoring project: preparing professional
      students for team work with health workers from urban communities.
AB  - Community Health Workers or CHWs (also known by a variety of alternative titles)
      are health workers drawn from communities to provide access to care for members
      of their communities. CHWs have been documented as effective in delivering a
      variety of services in a culturally-sensitive manner, and in providing a bridge
      between health professionals and underserved or minority communities. Yet, CHWs
      have not been well incorporated into interdisciplinary health care teams. The
      majority of health professionals are not even aware of the possible role and
      skills of CHWs. Believing that the best time to educate professionals about this
      valuable health worker and ensure that CHWs become part of interdisciplinary
      health care teams is during the student years, the Hunter College Schools of the
      Health Professions, and the Community Health Worker Network of New York City
      developed a pilot project, the Community Health Worker Cultural Mentoring
      Project. Community Health Workers, who were members of the Network, served as
      "community mentors" for health professions students drawn from the programs of
      community health education, nursing, and nutrition. CHWs worked with faculty of
      selected courses in each of the professional programs, and served as panelists in
      these courses, presenting information about health beliefs and alternative health
      practices of diverse cultural groups in communities of New York City. Class
      sessions were first held in the fall of 2004; subsequent sessions were held in
      following semesters. Approximately 40 students participated in 7 classes, with 6
      CHWs serving as mentors - two per class. At the end of the classroom
      presentations, students wrote reflections relating to their understanding of the
      CHW role and relevance for their future interdisciplinary practice. The majority
      of reflections met the goal of increasing professional students' understanding of
      the CHW role and skills. At this point, quantitative and qualitative data will
      need to be collected to verify the benefits of CHWs serving as cultural mentors,
      in order to determine the value of such panels being incorporated into health
      professions' education programs.

PMID- 19759985
TI  - Collaborating across borders: an American-Canadian dialogue on interprofessional
      health education.
AB  - For more than 35 years, interprofessional collaboration across the health and
      human service professions has been promoted as an important means to advance
      patient- or client-centered practice. Evidence demonstrates that collaborative
      care in certain circumstances can be more effective and efficient than other
      models. Over the past decade, in response to national calls to action, American
      and Canadian health and human service professionals and educators have renewed
      their focus on interprofessional education (IPE). As a result, recent investments
      have been made, and many interprofessional initiatives in higher education and
      health systems are underway to improve learning and health outcomes. These
      efforts are resulting in new evidence about student learning outcomes, team care
      and collaboration, lessons learned, curricular design, faculty development, and
      assessment and evaluation strategies. In spite of these efforts, there is a
      question as to whether much has really changed about the way health professionals
      are educated. In an effort to address the issue from an international
      perspective, professionals from a number of countries have been collaborating and
      sharing ideas on how to improve the situation. A very important effort is now
      being planned for an American-Canadian conference to be held October 24-26, 2007
      at the University of Minnesota. Called Collaborating Across Borders: An American
      Canadian Dialogue on Interprofessional Health Education, the conference will
      bring together leaders in the field to share best practices and chart a course to
      improve collaboration in health care.

PMID- 19759986
TI  - An investigation of the relationships among academic performance, clinical
      performance, critical thinking, and success on the physical therapy licensure
      examination.
AB  - BACKGROUND: The purpose of this study was to investigate relationships among
      clinical education performance, academic performance, critical thinking (CT)
      skills, and success on the National Physical Therapy Examination (NPTE) of
      graduates from a post-baccalaureate professional physical therapy program.
      Results of previous research comparing clinical and academic performance measures
      have been mixed. Academic performance measures have been linked to CT skills and
      NPTE performance but identifying factors related to success on the NPTE is
      unclear. Subjects. Forty-two graduates of one professional physical therapy
      program participated. The average age at completion of the program was 28.77
      years (SD 3.89) with a range of 24-40 years. The sample was primarily female
      (69%) and White/non-Hispanic (92.9%) with the remaining 7.1% representing
      Asian/Pacific Islander. METHODS AND MATERIALS: Data for this study collected at
      the end of the academic program included scores for the California Critical
      Thinking Skills Test (CCTST), ratings on the Clinical Performance Instrument
      (CPI), and final Grade Point Average (GPA). The remaining data was self-reported
      after graduation with each participant providing individual NPTE scores to the
      researcher. ANALYSIS: Analysis was performed using SPSS 12.0 to calculate a
      Pearson product moment correlation comparing the scores on the CCTST, CPI, GPA,
      and NPTE. Logistic regression analysis was used to determine the relationship
      between the outcome variable of passing the NPTE on the first attempt and scores
      on the CCTST, CPI and GPA. RESULTS: Two-tailed Pearson product moment correlation
      found significant relationships between CCTST scores and success on the NPTE
      (r=0.35; p=0.023) and between GPA and success on the NPTE (r=0.334; p=0.031).
      Logistic regression analysis results were not significant for any of the
      variables. CONCLUSION AND CONCLUSION: This research indicates a relationship
      exists between CCTST, GPA and the NPTE. Expanding the search for meaningful
      variables to include admission data or other program data might be helpful.

PMID- 19759987
TI  - Factors influencing student decision-making for clinical site selection.
AB  - PURPOSE: Entry into the professions of physical and occupational therapy requires
      the development of clinical skills acquired during clinical education
      experiences. There are many factors students need to consider when selecting a
      clinical education site. The purpose of this study was to identify factors which
      students perceive as important when selecting clinical sites in relationship to
      factors considered important by the Academic Coordinator of Clinical
      Education/Fieldwork Coordinator (ACCE/FWC). METHODS: A sample of convenience of
      100 participants was recruited from the University of Hartford Physical and
      Occupational Therapy programs. A nine-item Likert scale survey designed to
      identify factors that may be important to students when selecting clinical sites
      was completed. DATA ANALYSIS: Mean scores for student responses across three
      clinical education sessions were calculated and paired sample t-tests were used
      to determine significant differences in importance level. RESULTS: Findings from
      this investigation determined that financial considerations, type of specialty
      offered by the facility, fulfilling program requirements, and reputation of the
      facility were found to be statistically more important than the student's
      personal abilities. Personal ability was seen as significantly more important
      than desire to travel, proximity to school, and free/low cost housing provided by
      the facility (p < 0.01). CONCLUSION: Students select clinical sites primarily
      based on financial considerations, specialty offered, and program requirements.
      As opposed to the ACCE/FWC, students did not place a high value on the importance
      of personal abilities when selecting clinical education sites. CLINICAL
      RELEVANCE: The results of this study may help students develop an appreciation of
      the multitude of factors that should be considered in site selection, guide the
      ACCE/FWC in advising students, and assist clinicians to better understand how
      students select clinical sites.

PMID- 19759988
TI  - Knowledge and perceptions of tenure guidelines and criteria among allied health
      faculty: case study.
AB  - Current profiles of colleges/schools of allied health include nontraditional
      faculty, a limited percentage of faculty with doctoral degrees, and low
      research/scholarship productivity. This preliminary study asked allied health
      professionals to express their awareness of the tenure guidelines and criteria.
      Although a few variations in beliefs emerged based upon appointment type and
      personal experiences, three primary themes emerged: (1) limited understanding of
      the tenure guidelines and criteria, (2) research/scholarship is necessary, but
      perceived as difficult for allied health faculty, and (3) tenure is desirable,
      but is considered unachievable by some. This study, therefore, suggested that
      allied health faculty in higher education institutions perceived
      research/scholarship as central to achieving tenure, but were frustrated by the
      lack of formal guidance through the process.

PMID- 19759989
TI  - The European Master of Science in Occupational Therapy: a vision come true.

PMID- 19759990
TI  - NAPRAH symposium: enhancing faculty research career development: infrastructure
      and mentoring models.

PMID- 19759991
TI  - Continuing competence: an institutional look at engagement, link, and faculty
      perceptions.
AB  - This action research project addresses the issue of continuing competence from
      the viewpoint of allied health faculty members at a community college in
      Illinois. With input by and feedback from the faculty, the researcher describes
      how full-time allied health faculty members maintain their clinical competence,
      determines if efforts toward continuing competence are linked with academic
      responsibilities, and ascertains the role of the academic institution, the
      educational programs and the faculty members in ensuring continuing competence.
      Results of the study indicate that faculty members maintain their competence by
      attending continuing education courses, reading professional literature, and
      engaging in clinical work. There appears to be a disconnect, however, between
      these activities and the academic responsibilities of the faculty members. An
      analysis of perceptions reveals that the responsibility for ensuring continuing
      competence increases from the institutional level to the level of the faculty
      members, whereas accountability is shouldered by the faculty members and the
      educational programs.

PMID- 19759992
TI  - Interdisciplinary allied health education in treating older adults with low
      vision.
AB  - In 2000, the number of elderly citizens in the United States was 35 million, an
      increase of 3.7 million (11%) since 1990. Of these older adults, approximately
      1.3 million (4%) have a low vision impairment. Older adults make up two-thirds of
      those diagnosed with a visual impairment. Low vision impairment, which is
      different from the typical vision changes associated with aging, occurs because
      of a chronic visual disorder that cannot be corrected medically, surgically, or
      with conventional eyeglasses, most often resulting in disability. The leading
      causes of low vision impairment are diabetic retinopathy, cataract, glaucoma, and
      age-related macular degeneration. Combined with the other physical changes
      associated with aging, the development of a low vision impairment further
      challenges the functional performance and safety of those 65 and older.
      Furthermore, the psychological impact from the physical changes accompanying
      aging is compounded for those with a low vision impairment. In response to the
      health needs of all age groups, Healthy People 2010 has established overarching
      goals to increase quality and years of healthy life and eliminate health
      disparities. An interdisciplinary course for allied health students was developed
      to support future health care providers in improving quality of life for older
      adults with low vision and help decrease health disparities in this population.
      This paper reports on the pilot experience with this course.

PMID- 19759993
TI  - Knowledge and attitudes about fetal alcohol syndrome, fetal alcohol spectrum
      disorders, and alcohol use during pregnancy by occupational therapists in the
      Midwest.
AB  - Fetal Alcohol Syndrome (FAS) occurs in approximately 3 of 1,000 live births in
      the general population of the U.S. and is the leading known cause of mental
      retardation. The Midwest Regional Fetal Alcohol Syndrome Training Center
      (MRFASTC) surveyed 1,000 licensed occupational therapists (OT) of the American
      Occupational Therapists Association in a six-state Midwest region, including
      Missouri, Iowa, Nebraska, Kansas, Oklahoma, and Arkansas to assess knowledge and
      attitudes regarding FAS. Nearly 20% of the OTs responded. Of the respondents,
      nearly 94% regarded at least 1 drink per day as being 'heavy' in a pregnant
      woman. There was an increase in the number of respondents who thought it was
      acceptable to consume 1 drink or more with each advancing trimester of pregnancy.
      92% of the OTs indicated a willingness to counsel a mother of a child having FAS,
      but 96% indicated a poor to fair ability to select valid and reliable assessment
      instruments for screening a child for FAS. Only 6% of the OT respondents
      indicated a good-excellent ability to conduct brief interventions on alcohol
      cessation for women. The data collectively indicate OTs possess similarities to
      other health care providers, including physicians and psychologists, in the
      misunderstanding or deficits of knowledge and skills associated with FAS and that
      they are largely unprepared to provide intervention for women 'at risk' for FAS,
      or to recognize correctly FAS in children. There is a demonstrated need, and
      desire, by the practicing OTs for continued education related to alcohol abuse
      associated with FAS.

PMID- 19759994
TI  - Recruitment issues and potential solutions to increase rehabilitation science
      applications.
AB  - Recruitment of academically gifted students for Communication Sciences and
      Disorders, (Speech Language Pathology) Occupational Therapy and Physical Therapy
      programs has been a challenge for the past few years. A student survey was
      created to provide insight as to when in their academic development and what
      methods are used by students to make program selections. Outcomes from this study
      include: (1) when students made career choices; (2) what influenced them in their
      career choice, (3) how and why they selected their future profession, (4) the
      number of programs applied to, and (5) the reasons they selected our university.
      As a result of this survey, recruitment methods have been enhanced to more
      actively recruit students during high school and to ensure that personal,
      volunteer or work-experience is included in the recruitment process.

PMID- 19759995
TI  - Use of simulations to assess the injury evaluation and management skills of
      advanced student athletic therapists at a Canadian university.
AB  - Simulations can provide exposure to cases that might not present themselves
      during a practicum assignment or rotation, allow students to make decisions
      without risk to a real patient, expose students to critical situations requiring
      a rapid response, allow students to observe the consequences (good or bad) of
      their management choices, and provide training to maintain infrequently used
      skills. Simulation has been used in a variety of medical fields such as
      anesthesia, emergency medicine, military trauma medicine, intensive care, trauma,
      and surgical critical care. Within athletic training (athletic therapy, in
      Canada), simulations might maximize the retention of knowledge, could increase
      the number of clinical experiences encountered, and aid in the transfer of
      training to real-life settings. Simulations could also be used as a method for
      evaluating student performance and assessing whether instructional objectives
      have been met. The primary purpose of this study was to investigate the use of
      simulations for the formative assessment of student athletic therapists enrolled
      in a Canadian University athletic therapy program.

PMID- 19759996
TI  - Home-based exercise to alleviate fatigue and improve functional capacity among
      breast cancer survivors.
AB  - This pilot study examined the efficacy of two home-based exercise programs on
      alleviating fatigue and improving functional capacity in breast cancer survivors.
      Participants were randomly assigned into one of three groups: aerobic exercise
      (AE), resistance exercise (RE), or usual care control (CON). After receiving
      individualized instruction and training, participants assigned to the AE and RE
      groups were asked to perform the prescribed exercise(s) 3 times per week for 12
      weeks at home. Both groups were instructed to keep their perceived exercise
      intensity in the "fairly light" to "somewhat hard" range using the Borg Perceived
      Exertion Scale. All participants completed the revised Piper Fatigue Scale (PFS)
      and the 6-minute walk test (6MWT) at baseline and 12-week post-exercise program.
      Analysis of pre- and post-training data revealed a significant reduction in
      fatigue levels on the PFS among participants in the AE group (Z=2.521, one-tailed
      P=0.006), and a significant improvement in the distance of the 6MWT for the RE
      group (Z=2.366, one-tailed P=0.009) at the end of 12-week study period. No
      significant changes in fatigue or functional status were observed in the CON
      group. Findings provide preliminary support for RE as a viable strategy for
      improving functional capacity in breast cancer survivors, while AE may be more
      effective in attenuating cancer-related fatigue. Incorporating RE training for
      future research may help advance the growing body of knowledge in symptom
      management for breast cancer survivors.

PMID- 19759997
TI  - Using focus groups to assess presentation methods in a research seminar.
AB  - The purpose of this inquiry was to examine preferences between presentation
      methods among graduate students enrolled in a research seminar course.
      Participants consisted of 34 second year students enrolled in the Master of
      Science degree program in physical therapy in the College of Health Professions
      at the Medical University of South Carolina. All were required to present a
      published research article on the general topic of exercise in elderly
      individuals. However, before the student presentations took place, the instructor
      presented two different published research papers, both of which were done in
      sequential time segments during a single class period. For Time Segment 1, the
      instructor/author used a formal, "lecture," or "platform" type presentation,
      embellished by power point slides with textual information and graphs. For Time
      Segment 2, the instructor conducted an informal discussion of the background,
      methods, and findings of the research paper. After the presentations were
      completed, students were assigned to focus groups for the purpose of providing
      verbal and written feedback. Examination of the findings using content analysis
      revealed a variety of opinions regarding presentation techniques, but showed a
      general preference for the method employed in Time Segment 1. Among the reasons
      cited were the structure, the visual aids, and past familiarity and comfort with
      formal, "lecture" type presentations. Also noted was the predominant view that
      presenter style was a major factor in judging effectiveness. These findings merit
      further exploration of presentation styles and teaching methodologies for
      augmenting teaching effectiveness and enhancing the scholarship of teaching.

PMID- 19759998
TI  - Are physical therapy clinical instructors teaching the Institute of Medicine core
      competencies? An exploratory investigation using student perceptions.
AB  - The Institute of Medicine (IOM) has recommended instituting clinical education
      reforms to ensure all health profession graduates acquire five core competencies;
      providing patient-centered care, working in interdisciplinary teams, employing
      evidence-based practice, applying quality improvement and utilizing informatics.
      The IOM has identified 28 specific skills associated with these competencies.
      This qualitative, exploratory study was conducted to begin to examine the extent
      to which physical therapy clinical instructors provide students with instruction
      the students perceived as promoting the acquisition of these skills. METHODS: Two
      groups of physical therapy students enrolled in a 3-year DPT program (7 on a
      first-year clinical education experience and 17 on a final year experience)
      maintained journals describing the types of learning activities used by clinical
      instructors to promote the acquisition of the competencies. The authors employed
      NVivo qualitative data analysis software to code the journal entries using 28
      codes derived from the skills associated with the five core competencies.
      RESULTS: Of the 327 coded learning activities, just over 50% were related to
      skills associated with providing patient-centered care (21.4%) and working in
      interdisciplinary teams (30.0%). The remaining 49.6% of the learning activities
      cited by students were related to skills associated with employing evidence-based
      practice (18.3%), applying quality improvement (16.5%) and utilizing informatics
      (13.8%). DISCUSSION: Based on student perceptions, physical therapy clinical
      instructors are providing learning activities that allow students to acquire
      skills associated with all five of the IOM competencies. However, students
      reported the least emphasis on instruction pertaining to the competencies of
      applying quality improvement and utilizing informatics. CONCLUSION: This study
      supports the need for the profession of physical therapy to delineate formal and
      explicit clinical education instructional content and strategies to promote
      students' acquisition of the IOM core competency skills.

PMID- 19759999
TI  - Integrating professional behavior development across a professional allied health
      curriculum.
AB  - Professional behaviors are an integral part of clinical practice in all allied
      health and medical fields. A systematic process for instruction, the education,
      and development of professional behaviors, cannot be taught in the same way that
      memorization of human anatomy or medical terminology is taught. One cannot expect
      professional behaviors to just appear in an individual upon graduation and entry
      into a health care field. Professional behavior development is an essential
      component of physical therapy professional education and is clearly defined
      through the guiding documents of the American Physical Therapy Association, which
      include 'A Normative Model of Physical Therapist Professional Education,'
      'Evaluative Criteria for Accreditation of Education Programs for the Preparation
      of Physical Therapists,' and the 'Guide to Physical Therapist Practice.' Building
      a comprehensive and progressive curricular thread for professional behaviors can
      pose a challenge for a professional program and the core faculty. This paper will
      present a curricular model of weaving professional behaviors into a core entry
      level professional curriculum using a specific curricular thread, activities for
      different levels of students, and assessment at each point in the path. This
      paper will demonstrate the potential for universal application of a professional
      behaviors.

PMID- 19760000
TI  - Capturing patient encounters during health care provider training using Personal
      Digital Assistants.
AB  - Contemporary allied health education requires students experience both a depth
      and breadth of clinical encounters to prepare them to provide an increasingly
      broadening and evolving scope of practice. The Physician Assistant (PA) Studies
      program and the Family Nurse Practitioner (FNP) Graduate Nursing Program at
      Wichita State University, College of Health Professions joined forces to
      undertake a project to introduce Personal Digital Assistants (PDAs) to their
      students. One aspect of this project was the logging method used by students. The
      PA program further studied the tracking and used three different logging methods
      with three different cohorts to capture patent encounter data during standard
      clinical rotations: paper logs, web-based logs and Using Personal Digital
      Assistants (PDAs). Results indicate that patient encounter data were
      significantly better using PDAs than the other two methods. This report presents
      the background and results of the project as well as lessons learned.

PMID- 19760001
TI  - [Diagnosis and choice of surgical methods on traumatic temporomandibular joint
      ankylosis].
AB  - PURPOSE: The purpose of this study was to explore the diagnosis and operative
      methods for traumatic temporomandibular joint ankylosis. METHODS: Fourteen
      patients (8 females, 6 males; aged from 7 to 23 years, median age 17.5 years)
      with traumatic TMJ ankylosis of 1 to 15 years' duration, with a maximal mouth
      opening(MMO) from 0 to 1.0cm(average:0.46cm) preoperatively were included in this
      study. They were further divided into two types(I and II) based on false
      articulation medial to the analysis as shown by coronal computed tomography (CT)
      coronoid scan. 7 TMJs were treated with medial arthroplasty(MA), in which the
      lateral fusional bone was removed and the medial false articulation was retained
      for type I, 6 TMJs were treated with natural positional arthroplasty(NPA) in
      which the bony fusion between the condyle and glenoid fossa was separated and
      shaved, the disc was retained and repositioned for type II. Follow-up was carried
      out and the surgical effect was assessed based on clinical and imaging findings.
      Student's t test was conducted for comparison with SPSS15.0 software package.
      RESULTS: There was 9 TMJs from 7 patients for type I and 5 TMJs from 5 patients
      for type II as shown by CT. The mean postoperative MMO was 3.12cm, and the
      condylar shape was smooth on CT scan. There was significant difference between
      preoperative and postoperative MMO, P<0.01. There was no significant difference
      between MA and NPA, P>0.05. CONCLUSIONS: It is concluded that type I is more
      common in traumatic TMJ ankylosis than type II. The surgical effect of MA and NPA
      is good, with less injury, and is worthy of wide application.

PMID- 19760002
TI  - [Pedigree analysis and prosthodontic treatment of patients with dentinogenesis
      imperfecta type II].
AB  - PURPOSE: To study the heritable character and explore the prosthodontic treatment
      of opalescent dentin, also known as dentinogenesis imperfecta type II(DGI-II).
      METHODS: Pedigree analysis was performed in the family members of patients with
      DGI-II found in Shanghai. The proband was treated with ceramometal restorations
      and investigated the treatment status of the DGI-II affected individuals in the
      family. RESULTS: Five sequential generations with DGI-II were found in this
      family. The prevalence of later generation was approximately 50%. The rate of
      prosthodontic treatment was 90% nearly, including ceramometal restorations in the
      most of the patients and removable partial dentures in the others. The esthetic
      and mastication functions of the patients were good after treatment. CONCLUSIONS:
      DGI-II showed a autosomal dominant pattern of inheritance. Ceramaometal
      restorations can prevent the affected teeth from abrasive and fracture, and also
      can help rehabilitate the esthetic and mastication functions of the teeth.

PMID- 19760003
TI  - [Study of the crestal bone height and root length technique change of impacted
      canines treated by modified Nance arch technique].
AB  - PURPOSE: The purpose of this study was to evaluate the crestal bone height and
      root length change after orthodontic treatment of impacted canines with modified
      Nance arch technique. METHODS: 8 maxillary impacted canines were treated with
      modified Nance arch technique. The canines of other side which were naturally
      erupted were used for self-control. Pre-treatment and post-treatment panoramic
      radiographs were measured and the following data was collected: (1)The distance
      of the impacted canine migration and the angle change of the impacted canine;
      (2)Crestal bone height and root length between previously impacted canines and
      adjacent lateral incisors and premolars(experimental)and contralateral control
      teeth. The crestal bone height and root length were compared using a paired t
      test with SPSS11.0 software package. RESULTS: The mean distance of the impacted
      canine migration was 18.43 mm and the mean angle change on the panoramic
      radiograph was 32.7 degrees. No difference was found in the crestal bone height
      and the root length between the adjacent lateral incisors and
      premolars(experimental) and the contralateral control teeth(P>0.05). CONCLUSION:
      The combination of modified Nance arch with straight wire arch technique is a
      valid method to treat maxillary impacted canines.

PMID- 19760004
TI  - [Effect of pulse Nd:YAG laser on micro-tensile bond strength of non-carious
      sclerotic dentin to resin].
AB  - PURPOSE: To evaluate the microtensile bond strength of pulse Nd:YAG laser to non
      carious sclerotic dentin. METHODS: Ten extracted human teeth with dental
      attrition on occlusal surface were cut into nearly equal halves(about 12
      mm(2)),and randomly divided into two groups with 10 in each group.All teeth were
      bonded using an all-in-one self-etch dentin adhesive(Adper Prompt L-Pop) to
      composite resin after the teeth in the experimental group were processed with
      pulse Nd:YAG laser(1 W,10 Hz). After 24 hours,under copious water spray the teeth
      were sectioned into 0.8 mm x 0.8 mm columns with silicon carbide dish at low
      speed. The microtensile bond strengths of samples were measured.Each fractured
      specimen was examined under stero-microscope. Paired t test was used for analysis
      of the microtensile bond strengths between the two groups with SPSS13.0 software
      package. RESULTS: The microtensile bond strength in the experimental group and
      control group was (18.94+/-6.81)MPa and (15.76+/-5.61)MPa, respectively, the
      difference of these two groups was statistically significant(P<0.05). The
      fractured adhesive dentin surface was mainly adhesive failure mode. CONCLUSION:
      Pulse Nd:YAG laser(1 W,10 Hz) can improve the strength of composite resin bonding
      to sclerotic dentin.

PMID- 19760005
TI  - [The stability of soft tissue changes in patients with skeletal Angle Class III
      malocclusion after orthodontic-orthognathic treatments].
AB  - PURPOSE: The purpose of this study was to analyze the changes of soft tissues at
      each treatment stage in patients with skeletal Angle Class III malocclusion after
      orthodontic-orthognathic surgery and to assess the long-term stability after
      treatments. METHODS: 24 patients with skeletal Angle Class III malocclusion were
      included in this study. Standardized lateral cephalograms at the following stages
      were taken for each patient:T(0)-before treatment; T(1)-3 months after surgery;
      T(2)-1 year after surgery; T(3)-3 years after surgery. A total of 13 soft tissue
      landmarks were selected and the angles at different stages were evaluated.
      SPSS12.0 software package was used to calculate x and s,q test was used to
      evaluate the changes of the soft tissues. RESULTS: (1)Comparison between stage
      T(0) and T(1):x all landmarks had significant difference except the angle of A'UL
      B'LL. (2)Comparison of the angles between stage T(1) and T(2) : the angles of S
      N'-B, G-Sn-Pos, Ns-Sn-Pos, FH-SnPos and Z had significant difference.
      (3)Comparison of the angles between stage T(1) and T(3) :the angles of S-N'-B',G
      Sn-Pos,Ns-Sn-Pos,FH-SnPos,Z and Ns-Prn-Pos had significant differences.
      (4)Comparison of the angles' changes between stage of T(2) and T(3): only G-Sn
      Pos had significant diversity. CONCLUSIONS: Angles related with Pos are more
      likely to relapse, but on the whole, the treatment effect is stable.

PMID- 19760006
TI  - [The effect of different gutta-percha master cones on first penetration depth of
      spreader and apical microleakage].
AB  - PURPOSE: This study was to evaluate the effect of different master cones on
      apical microleakage through comparing first penetration depth of spreader and the
      leakage concentration of glucose in the curved root canal of the extracted
      posterior teeth filled with different gutta-percha master cones. METHODS: Sixty
      six extracted roots of human posterior teeth with a single, curved canal were
      collected and divided into five experimental groups of 11 roots in each group
      (Group A:master cone 0.06 tapered, 25#; Group B: 0.06 tapered, 20#; Group C: 0.04
      tapered, 30#; Group D: 0.04 tapered, 25#; Group E: 0.02 tapered, 25#) using cold
      lateral condensation as positive control group(group F, AH-PLUS sealer) of 5
      roots and negative control (group G, integrated teeth) of 6 roots. The first
      penetration depth of spreader and the concentration of glucose in apical
      reservoir at 1, 2, 4, 7, 10, 15, 20 and 30 days were measured, respectively. The
      data was analysed with ANOVA and LSD test using SPSS 16.0 software package.
      RESULTS: The value of working length minus the first penetration depth of
      spreader in group D was significantly smaller than that in group A and group
      C(P<0.05),and that in group E was significantly smaller than that in group A
      ,B,C(P<0.05), but no significant difference(P>0.05) in other groups. The
      concentration of leakage glucose in group F was significantly higher than that in
      the other six groups(P<0.05),and there were no significant difference in the five
      experimental groups (P>0.05),which had no significant difference from the
      negative control group G(P>0.05). CONCLUSIONS: Choosing smaller tapered master
      cone could get better apical filling in curved canals, but it has no superiority
      in apical sealing in short time.

PMID- 19760007
TI  - [Arnett analysis of the correlation between midfacial soft and hard tissues].
AB  - PURPOSE: To study the correlation between midfacial soft tissues and craniofacial
      hard structures of malocclusions with different skeletal patterns by Arnett
      analysis. METHODS: 60 children (26 males, 34 females), aged from 12 to 16 years,
      who had no orthodontic treatment, congenital craniofacial deformity and
      remarkable facial asymmetry, were divided into 3 groups according to ANB. Lateral
      cephalograms were taken when the patients' heads in natural positions and metal
      beads placed on right midface according to Arnett analysis. Statistical analysis
      was performed using SPSS10.0 software package and the values of midfacial soft
      tissues were compared among groups with one-way ANOVA. In addition, correlation
      analysis was conducted to determine the correlation between soft and hard
      tissues. RESULTS: The values were significantly varied with different ANB
      (P<0.01) such as overbite, overjet, orbital rim, cheek bone, Md1, lower lip
      anterior, throat length and facial angle. Mx occlusal plane, pogonion',
      subnasale'-pogonion', orbital rims, subpupil, alar base, cheek bone had
      significant correlation with SNB, while values like cheek bone and alar base had
      significant correlation with ANB. CONCLUSIONS: The soft tissues of midface are
      greatly correlative to craniofacial hard structures such as the sagital
      relationship of upper and lower jaws.

PMID- 19760008
TI  - [Dental rehabilitation of using telescope-based preventive, removable prosthesis
      system].
AB  - PURPOSE: This paper aimed at introducing an improved konuskrone telescope system
      with the advantages of both the fixed denture and the removable, partial dentures
      for clinical application in restoring the missing teeth. METHODS: The konuskrone
      telescope system was modified and named as the Preventive, Removable Prosthesis
      (PRP) system in which the inner crown was fixed on the abutment teeth, and the
      outer crown with bridge, rest and connector together as a whole was formed a
      removable unit. RESULTS: The clinical case reports indicated that the PRP system
      saved at least 50% cut-out of the abutment teeth,and helped the patients improve
      their oral hygiene,cure and rehabilitation. CONCLUSIONS: The PRP system with the
      good appraisal of the fixed denture and the removable, partial denture and
      without the shortcomings of both dentures provides an option for rehabilitation
      of the missing teeth.

PMID- 19760009
TI  - [First molar extraction in malocclusion: an analysis of 20 consecutive cases].
AB  - PURPOSE: To study the feasibility and orthodontic effect of decayed first molar
      extraction in malocclusion. METHODS: 20 cases with first molar extraction in
      malocclusion were chosen for this study. There were 3 males and 17 females, aging
      from 13.5 to 22 years with an average age of 15.6 years . 7 cases were treated
      with extraction of two lower first molars, 5 cases with extraction of one lower
      first molar, 2 cases with extraction of four first molars, 2 cases with
      extraction of one lower first molar and upper first molar, 4 cases with
      extraction of one upper first molar. All patients were treated with 0.018
      edgewise appliance or 0.018 straightwire appliance. The procedure included
      bonding brackets, putting arch wire, leveling dentition, closing extraction space
      and adjusting occlusal relationships routinely. RESULTS: When treatment finished,
      all the 20 cases gained satisfactory results, all the teeth lined up in order
      ,anterior teeth gained correct overbite and overjet, midline was alignment, molar
      space was completely closed, occlusion was perfect, the occlusion and facial
      profile were improved. CONCLUSION: The treatment of decayed first molar
      extraction in malocclusion could retain more healthy teeth, gain satisfactory
      orthodontic results, improve the occlusion.

PMID- 19760010
TI  - [Clinical evaluation of root canal obturation of GuttaFlow].
AB  - PURPOSE: To evaluate the clinical effects of GuttaFlow on root canal obturation.
      METHODS: 314 teeth were divided into 2 groups randomly.The GuttaFlow plus gutta
      percha cone was used to fill root canals in the experimental group and
      Endomenthasone sealer plus gutta-percha cone was used in the control group. The
      filling time, the effect of root canal obturation by X-ray, the occurrence of
      pain during the filling operation and after treatment were recorded. The data was
      analyzed with SPSS13.0 software package. RESULTS: The filling time in the
      experimental group was significantly less than that in the control group by rank
      sum test (P<0.01).There was no significant difference between the two groups on
      both the root filling effect and occurrence of pain by Chi-square test (P>0.05).
      CONCLUSIONS: The root canal obturation of GuttaFlow plus gutta-percha cone is an
      easier and faster filling system for root canals. There is no significant
      difference on root filling effect and occurrence of pain between the GuttaFlow
      and the normal lateral compaction technique. It is one choice of clinical
      techniques for root canal obturation.

PMID- 19760011
TI  - [Clinical study of maxillary protraction combined with maxillary molar
      distalization appliance therapy on cross bite and crowding malocclusion].
AB  - PURPOSE: To investigate the influence of maxillary protraction combined with
      maxillary molar distalization appliance therapy on skeletal Class III cross bite
      malocclusion. METHODS: 60 patients with cross bite and crowding malocclusion were
      treated with maxillary protraction combined with maxillary molar distalization
      appliance. The arch length was analyzed before wearing appliance (T1), after
      debonding appliance(T2), and one year after debonding appliance(T3). SPSS10.0
      software package was used for ANOVA. RESULTS: Before therapy, the maxillary arch
      length was not enough with arch length discrepancy. After active treatment, the
      device had extended the length of the upper dental arch significantly to relieve
      crowding and change the cross bite. Esthetics were greatly enhanced. CONCLUSIONS:
      Maxillary protraction combined with maxillary molar distalization appliance
      therapy change the maxillary arch length. However, further study is necessary to
      understand the long-term clinical effect.

PMID- 19760012
TI  - [Biological characteristic comparison between long junctional epithelium cells
      and junctional epithelium cells].
AB  - PURPOSE: To culture long junctional epithelium (LJE) cells in vitro and compare
      its biological characteristics with junctional epithelium (JE) cells. METHODS:
      LJE samples were collected from the patients with chronic periodontitis during
      flap surgery. Sulcular parts of tissues were removed by sterile scissor then
      enzymatic method and keratinocyte-serum free medium (KSFM) were used for
      culturing. JE samples were obtained from healthy bicuspid premolars or third
      morlars for orthodontic or impaction reasons and the cells were cultured in the
      same way as LJE. The two types of cells were compared in cell morphology,
      dimension,viability, proliferation, apoptosis and cytokeratin expression by means
      of cytoanalyzer, confocal laser scanning microscope and flowcytometry.
      Statistical analysis was performed using SPSS11.5 software package for
      independent-samples t test. RESULTS: LJE and JE cells exhibited similar cell
      morphology. Although the viability of LJE cells were lower than JE cells, there
      were no statistical significance (P>0.05). The mean diameter and volume of LJE
      cells were (19.03+/-0.19)microm and (4.29+/-0.19)x10(3) fL versus (17.16+/
      0.95)microm and (3.20+/-0.52)x10(3)fL of JE cells (P<0.05). The doubling time of
      LJE cells, was longer than that of JE cells.CK19 expression of LJE cells was
      weaker than of JE cells and there were no difference in the expression pattern of
      CK6 and CK13. Compared with control cells, the early- and late-stage apoptosis
      ratio of LJE cells were (4.62+/-2.16)% and (9.46+/-1.84)%, respectively which
      were all higher than JE cells which were (0.47+/-0.63)% and (3.84+/-0.98)%
      (P<0.05). CONCLUSION: There is difference between LJE and JE cells in dimension,
      CK19 expression, proliferation time and apoptosis. This study provides some
      clinical significance and aid in understanding the biological characteristics of
      LJE and the healing process of periodontitis.

PMID- 19760013
TI  - [The effect of B lymphocytes on immune response of periodontal bacteria and
      osteoclast differentiated reactor-RANKL expression].
AB  - PURPOSE: To study whether B lymphocytes involve in bone resorption in periodontal
      disease by evaluating RANKL expression of B lymphocytes in immune response to
      aggregatibacter actinomycetemcomitans (Aa). METHODS: The expression of mRNA
      transcripts involved in day 1 and day 7 responses of cytokines in cultured rat
      splenocytes was determined by RT-PCR; The percentage of RANKL-expressing IgG
      positive cells by B cells in cultured rat splenocytes was measured by flow
      cytometry; and B lymphocytes capacity for induction of osteoclast differentiation
      was evaluated by TRAP staining. SPSS 10.0 software package was used for
      statistical analysis. RESULTS: The expression of IL-4 and IL-10 in cultured cells
      was not changed in the presence of Aa on day 1, after culture for 7 days; The
      percentage of B lymphocytes, all RANKL mRNA transcripts and percentage of RANKL
      expressing IgG positive cells were significantly increased in the presence,
      compared to the absence of Aa. These increases were considerably greater in cells
      isolated from immunized than non-immunized rats. B cells from Aa immunized rats
      significantly increased induction of osteoclast differentiation (P<0.01), and
      addition of human OPG-Fc into the culture significantly inhibited its induction
      (P<0.05), and was RANKL-independent. CONCLUSION: B lymphocytes contribute to bone
      resorption in periodontal disease through involving in the immune response to Aa,
      up-regulation of RANKL expression and increasing induction of osteoclast
      differentiation.

PMID- 19760014
TI  - [An in vitro evaluation of the antibacterial activity of chitosan-based
      thermosensitive hydrogel against periodontal pathogens].
AB  - PURPOSE: To evaluate the in vitro antibacterial activity of chitosan -
      quaternized chitosan/alpha, beta-glycerophosphate (CS-HTCC/GP) thermosensitive
      hydrogel against three periodontal pathogens- P. gingivalis, P. intermedia, and
      A. actinomycetemcomitans. METHODS: An agar diffusion method was used to assess
      the antimicrobial property of CS-HTCC/GP thermosensitive hydrogel with minimum
      inhibitory concentration (MIC) and inhibitory zone measurement. SPSS13.0 software
      package was used for Student's t test. RESULTS: Three periodontal pathogens
      strains were all susceptible to CS-HTCC/GP thermosensitive hydrogel. Both matrix
      of thermosensitive hydrogel and antibiotic exhibited stronger antibacterial
      activity especially when they were combined. CONCLUSIONS: CS-HTCC/GP
      thermosensitive hydrogel is not only as the vehicle of antibiotics which joins
      the local drug delivery system but as an activator which takes part in the
      antibacterial process.

PMID- 19760015
TI  - [Effect and mechanism of matrine on adhesion and invasion of salivary gland
      adenoid cystic carcinoma cells in vitro].
AB  - PURPOSE: To investigate the effect and mechanism of matrine on adhesion and
      invasion of human adenoid cystic carcinoma ACC-M cells in vitro. METHODS: MTT
      assay was used to examine the effect of matrine on proliferation of ACC-M cells
      treated after 1 day to 3 days. Byden chamber assay was performed to detect the
      effect of matrine on invasion capacity of the cells; Effect on adhesion potential
      of ACC-M cells was tested by cell matrigel adhesion assay. Mechanism of
      inhibitory adhesion and invasion was investigated by expression of E-cad protein.
      The results was analyzed by SPSS11.0 software package. RESULTS: Matrine could
      inhibit the proliferation of ACC-M cell lines with apparent dose-dependent and
      time-dependent effect. Matrine significantly inhibited adhesion and invasion
      capacity of ACC-M cell lines in vitro with concentration increasing. The
      expression level of E-cad was significantly increased compared with the untreated
      group in ACC-M cell lines. CONCLUSIONS: Matrine can inhibit the adhesion and
      invasion capacity of ACC-M cell lines in vitro. Mechanism of the inhibition
      effect may be related to over expression of E-cad protein.

PMID- 19760016
TI  - [A scanning electron microscopic study of root surface following mini-implant
      anchorage for maxillary incisors intrusion].
AB  - PURPOSE: To establish an animal model for maxillary incisors intrusion with mini
      implant as the anchorage and study the effect on the surface morphology of
      cementum after the force had been given. METHODS: 9 dogs were selected and
      randomly divided into 5 groups, group I was the control group(1 dog) with no
      force given; groups II,III,IV,V were experimental groups (2 dogs each). Mini
      implants were inserted into the labial alveolar bone between the roots of second
      and third maxillary incisors on both sides, 100 gram force was imposed on the
      first and the second incisors on both sides.The animals were sacrificed at the
      end of 1, 2, 4,12 weeks (activation for 4 weeks,then retention for 8 weeks after
      force removal) respectively after activation.Scanning electron microscopy was
      used to examine the surface of the cementum. RESULTS: In group II, the surfaces
      of root tip had a little scratch, which was small,confined. In group III, near
      the apical 1/3 of root, lacunas were fused, but no dentin exposed. In group IV,
      at the junction of the apical 1/3 and the middle 1/3 of the root, lacunas went
      deep into the dentin,which were wide and serious. In group V, the surfaces of
      lacunas were low ,smooth and even. CONCLUSIONS: As the intrusion goes on, the
      area of absorption expands from the root tip to neck. Root resorption increases
      with the duration of the applied force prolonged and repair of the cementum
      occurs at the resorbed area after force removal.

PMID- 19760017
TI  - [Effect of HA/TiO2 coating titanium surface on the growth of MG63].
AB  - PURPOSE: To evaluate the bioactivity of titanium surface treated by micro-arc
      oxidation (MAO) combined with ion beam assisted deposition (IBAD). METHODS:
      Titanium surfaces were treated by machined(S0), micro-arc oxidation(S1) and micro
      arc oxidation combined with IBAD(S2), respectively. The topography and roughness
      of surfaces were determined by profilometer, and the bioactivity of the surface
      was evaluated by CLSM, MTT assay and ALP activity of cells. The data was analyzed
      by one-way ANOVA using SPSS11.0 software. RESULTS: The surfaces of S2 group were
      smoother than those of S1 group. On day 5, the OD value of S2 group was the
      highest among the three groups.10 days later, ALP activity on S1 and S2 groups
      were higher than that of S0 group. CONCLUSIONS: It is concluded that IBAD
      technique which provides HA coating on MAO surface could reinforce the
      bioactivity of micro-arc oxidation and could have a rapid osseointegration.

PMID- 19760018
TI  - [In vitro activity of matrine against Candida albicans biofilms].
AB  - PURPOSE: To establish a model of Candida albicans biofilms and to examine the
      effect of matrine on C.albicans biofilms and ultrastructure. METHODS: C. albicans
      collection strain ATCC76615 was obtained and propagated. Biofilms were formed in
      96-well microtiter plates. Antifungal susceptibility testing of C. albicans
      biofilms were assessed with the tetrazolium salt (XTT) reduction assay. Confocal
      laser scanning microscopy (CLSM) and dead/live fluorescent staining technique
      were combined to detect the effects of Matrine on preformed C. albican biofilms'
      composition and ultrastructure. RESULTS: Matrine was active against different
      growth stages (early,middle,mature) of biofilms; The bioactivity and drug
      resistance of C. albican biofilm increased with culturing time. CLSM showed that
      C. albicans biofilms were inhibited and growth were predominantly composed of
      yeast cells and pseudohyphae. CONCLUSIONS: This study demonstrates that Matrine
      has potent activity against C.albicans biofilms in vitro and potential
      therapeutic implication for biofilm-associated candidal infections.

PMID- 19760019
TI  - [In vitro study of marginal microleakage of Clearfil S3 BOND adhesive systems and
      Majesty composite resin].
AB  - PURPOSE: To evaluate the microleakage of standard box-type cavity filled with
      Clearfil S3 BOND self-etch adhesive systems and Majesty composite resin. METHODS:
      40 permanent molars were randomly divided into experimental and control groups,
      20 of each . The box-type cavities, 3mm in length and width and 2mm in depth,
      were prepared at the cemento-enamel junction on buccal surface of forty permanent
      extracted teeth. According to grouping, the experimental group was filled with
      Clearfil S(3) BOND self-adhesive systems and Majesty composite resin, and the
      control group was filled with 3M Adper Prompt self-adhesive and Filtek Z350
      composite resin. After thermal circulation(2000 times, 5 degrees centigrade-55
      degrees centigrade) and soaked for 24 hours in 2% methyl blue solution, the
      samples were cut through the midline of the restoration and the leakage depth was
      measured with vernier caliper. The microleakage degrees and microleakage depth of
      2 groups were analyzed with SPSS 17.0 software package for Mann-Whitney U test
      and independent-samples t test. RESULTS: Microleakage was observed in both
      groups. But the microleakage degrees and microleakage depth of 2 groups had no
      significant difference (P>0.05). CONCLUSION: The marginal sealibility of Clearfil
      S(3) BOND self-adhesive systems and Majesty composite resin is as good as Adper
      Prompt self-adhesive and Filtek Z350 composite resin,it may be an ideal clinical
      restoration material.

PMID- 19760020
TI  - [The inhibitory effect of calcitriol on the proliferation of hPDLCs populations
      of different vitamin D receptor Fok I genotypes].
AB  - PURPOSE: The study was designed to investigate the effect of calcitriol [1,25
      (OH)(2)D(3),VD(3)] on the proliferation of human periodontal ligament cells
      (hPDLCs) and to analyze the influence of vitamin D receptor Fok I polymorphism
      (rs2228570, T/C) on the effect. METHODS: Primary cultures of hPDLCs populations
      from individual donors were established. Restriction fragment length polymorphism
      method was used to detect the genotypes of the Fok I site. The fourth passage
      hPDLCs populations of FF, Ff and ff genotypes were respectively treated with 0.1%
      ethyl alcohol (control) or 10(-14)-10(-8) mol/L VD3 for 1, 3, 5 and 7 days. MTT
      method was performed to evaluate the proliferation of hPDLCs. The data was
      analyzed by one-way ANOVA and LSD Post Hoc test using SPSS 11.5 software package.
      RESULTS: VD3 inhibited the proliferation of hPDLCs populations of three genotypes
      in a time- and concentration-dependent manner. 10(-8) mol/L VD(3) exerted the
      most powerful inhibition compared with controls and other concentrations and the
      highest inhibition occurred on day 5 or day 7. Compared with the corresponding
      controls, the lowest concentrations of VD3 which exerted statistically
      significant inhibitory effect on the proliferation of hPDLCs populations were
      listed as follows: 10(-12) mol/L for the hPDLCs population of FF genotype
      (P<0.01), 10(-10) for Ff genotype (P<0.01) and 10(-8) mol/L for ff genotype
      (P<0.01). The highest proliferation inhibitory rate exerted by 10(-8) mol/L VD(3)
      on the ff population was 16.93%,which was significantly lower than FF (31.20%,
      P<0.05) and Ff (29.68%, P<0.05). On day 3 and day 5, 10(-8) mol/L VD(3) exhibited
      the strongest suppression on the proliferation of hPDLCs population of FF
      genotype, followed by Ff and ff genotypes (P<0.01). CONCLUSION: VD(3) can
      significantly inhibit the proliferation of hPDLCs, which may be affected by VDR
      Fok I polymorphism.

PMID- 19760021
TI  - [Continuous observation of canal aberrations in S-shaped simulated root canal
      prepared by hand-used ProTaper files].
AB  - PURPOSE: To observe the formation of canal aberrations in S-shaped root canals
      prepared by every file of hand-used ProTaper. METHODS: Fifteen S-shaped simulated
      resin root canals were selected. Each root canal was prepared by every file of
      hand-used ProTaper following the manufacturer instruction. The images of canals
      prepared by S1, S2, F1, F2 and F3 were taken and stored, which were divided into
      group S1, S2, F1, F2 and F3. One image of canal unprepared was superposed with
      the images of the same root canal in these five groups respectively to observe
      the types and number of canal aberrations, which included unprepared area, danger
      zone, ledge, elbow, zip and perforation. SPSS12.0 software pakage was used for
      Fisher's exact probabilities in 2x2 table. RESULTS: Unprepared area decreased
      following preparation by every file of ProTaper, but it still existed when the
      canal preparation was finished. The incidence of danger zone, elbow and zip in
      group F1 was 15/15, 11/15, 4/15, respectively, which was significantly higher
      than that in group S2(2/15,0,0) (P<0.001). Ledge appeared after prepared by F2,
      and increased sharply in group F3. None perforation was found in all groups.
      CONCLUSIONS: The incidence of canal aberrations begins to increase after prepared
      by finishing files of ProTaper.The presence of unprepared area suggests that it
      is essential to rinse canal abundantly during complicated canal preparation and
      canal antisepsis after preparation.

PMID- 19760022
TI  - [The influence of toothguide training box on shade matching veracity].
AB  - PURPOSE: The aim of the study was to evaluate the influence of toothguide
      training box(TTB) on shade matching veracity, and compare the differences of
      influence on shade matching veracity of tabs of shadeguide and on that of tabs
      out of shadeguide. METHODS: 31 graduated students who had 1 to 5-year clinical
      experience without color blindness were trained by TTB once a week for 3 weeks.
      Elapsed time and scores from the training system were recorded each time. And
      everyone was tested by 29 tabs of Vita 3D-Master shadeguide and 7 tabs out of
      Vita 3D-Master shadeguide before the first training as the base line and tested
      again after the last training as the test after training. SPSS 10.0 software
      package was used for analysis. The variances of scores and elapsed time were
      analyzed by ANOVA, and the differences of veracity between tabs of shadeguide and
      that of tabs out of shadeguide by Wilcoxon signed ranks test. RESULTS: The scores
      of the tests were rising via training. There was significant difference (P<0.01)
      between the first (900.29+/-51.68) and the third training (933.81+/-32.94). The
      elapsed time was turning shorter via training. There is significant difference
      (P<0.01) between the first [(46.29+/-13.29)min] and the second training [(32.68+/
      8.81)min], and also between the first and the third training (30.00+/-7.07)min.
      The veracity of test after training was higher than the veracity of base line. A
      significant difference (P<0.01) of shade matching veracity was demonstrated
      between base line and test after training in both tabs of shadeguide (60.37%+/
      18.33%,46.08%+/-22.04%) and the total (37.10%+/-11.58%,28.34%+/-11.73%), but that
      difference in tabs out of shadeguide (13.82+/-14.98%,10.60%+/-11.65%) was not
      significant(P>0.01). CONCLUSION: TTB can improve the shade matching ability of
      prosthodontists, but has limited influence on the shade matching ability of tabs
      out of shadeguide.

PMID- 19760023
TI  - [Assessment for hospital research foundation of Shanghai Research Institute of
      Stomatology].
AB  - PURPOSE: To evaluate 10 year's performance of research foundation of Shanghai
      Research Institute of Stomatology, and to analyze the relationship between input
      and output. METHODS: An evaluation target system for hospital research foundation
      projects was designed according to literature research and experts' consultation.
      Statistical measures such as general descriptive analysis and multiple stepwise
      regression were used to analyze the influential factors and the relationship
      among research output, financial and human input via Excel 2003 and SPSS11.0
      software package. RESULTS: An evaluation target system was set up and applied to
      evaluate the output of hospital research foundation. The performance showed the
      sustained and stable contribution to the comprehensive research output of the
      hospital. The education level of the researchers was found to be the key
      influential factor. CONCLUSIONS: Hospital research foundation plays an important
      role in cultivating research projects and construction echelon personnel. The
      whole process of management should be strictly implemented on the projects, and
      incentive measures are preferable to be set up.

PMID- 19760024
TI  - [Development of bone-anchored surgically assisted rapid maxillary expansion].
AB  - The indication of surgically assisted rapid maxillary expansion is to correct the
      transverse maxillary deficiencies. With the purpose of increasing the width of
      narrow upper dental arch and of the nasal cavity, maxillary expansion can provide
      dental arch space for teeth alignment, and improve the masticatory efficiency and
      nasal respiration. Comparing to teeth anchored palatal expansion, bone anchored
      technique can reduce the periodental damage and root resorption of supporting
      teeth. The results of bone anchored method are stable and the relapse is low for
      long term follow-up. More time on surgical duration is the main disadvantage.
      Some sorts of bone anchored appliance are widely used in clinic.

PMID- 19760025
TI  - [Treatment of zygomatio- orbital fractures with small local incisions: report of
      32 cases].
AB  - PURPOSE: To evaluate the surgical result of small local incisions in the
      treatment of zygomatio-orbital fractures. METHODS: 32 patients with zygomatio
      orbital fractures were operated on with two or more kinds of incisions, including
      subciliary incision, lateral eyebrow incision, transverse incision along the
      superior margin of zygomatic arch, oral vestibular incision, maxillary sinus
      incision, the original wound according to the area and type of the fractures. The
      fracture line was exposed via the small local incisions and fixed with micro
      titanium plates. The therapeutic effectiveness was evaluated 3 to 6 months after
      operation. RESULTS: All patients had primary healing without apparent scars in
      the face,except that one patient developed mild ectropion and two had temporary
      paralysis of the temporal branches of the facial nerve. The function of the eyes
      recovered completely, while the jaw movement improved significantly. The facial
      appearance recovered to normal height and width and the bilateral face became
      symmetrical. CONCLUSION: Treatment of zygomatic-orbital fractures with small
      local incisions is minimally invasive and the facial appearance and function can
      be recovered significantly with few complications.

PMID- 19760026
TI  - The effects of polymorphisms in methylenetetrahydrofolate reductase (MTHFR),
      methionine synthase (MTR), and methionine synthase reductase (MTRR) on the risk
      of cervical intraepithelial neoplasia and cervical cancer in Korean women.
AB  - The purpose of the study was to investigate the association between cervical
      cancer risk and single-nucleotide polymorphisms (SNPs) in three one-carbon
      metabolism genes, methylenetetrahydrofolate reductase (MTHFR), methionine
      synthase (MTR), and methionine synthase reductase (MTRR) in Korean women. Twelve
      SNPs were identified in MTHFR, MTR, and MTRR in the 927 case-control samples,
      which included 165 cervical intraepithelial neoplasia 1 (CIN1), 167 cervical
      intraepithelial neoplasia 2 and 3 (CIN2/3), 155 cervical cancer patients, and 440
      normal controls. The frequencies of the genotypes and haplotypes were assessed in
      the controls, CINs, and cervical cancers. Individual carriers of the variant
      allele C of MTHFR A1298C (rs1801131) had a 0.64-fold [95% confidence interval
      (CI): 0.42-0.98] decreased risk for CIN2/3 compared with common homozygotes.
      However, no significant association was found between most other variants and
      cervical cancer risk. The results also identified an increased CIN1 risk in
      carriers with at least one copy of haplotype 3 in the MTHFR gene (odds ratio,
      1.88; 95% CI: 1.03-3.42). In conclusion, there was no significant association
      between most SNPs in MTHFR, MTR, or MTRR and the risk of CIN and cervical cancer
      in Korean women. In addition, there was no significant association of MTHFR
      haplotypes with risk of CIN2/3 and cervical cancer.

PMID- 19760027
TI  - Association of common polymorphisms in IL10, and in other genes related to
      inflammatory response and obesity with colorectal cancer.
AB  - OBJECTIVE AND METHODS: The association of 17 candidate single nucleotide
      polymorphisms (SNPs) in IL10 and other immune response genes (CRP, TLR4, IL6,
      IL1B, IL8, TNF, RNASEL) and genes related to obesity (PPARG, TCF7L2, ADIPOQ, LEP)
      with colorectal cancer was investigated. Haplotype tagging SNPs were chosen for
      IL10, CRP, and TLR4. Incident colorectal cancer cases (n = 208) and matched
      controls (n = 381) were identified between baseline in 1989 and 2003 among
      participants in the CLUE II cohort. Odds ratios (OR) and 95% confidence intervals
      (95% CI) were estimated using conditional logistic regression. RESULTS: Compared
      with the AA genotype at the candidate IL10-1082 locus (rs1800896), carrying one
      (OR, 0.79; 95% CI, 0.53-1.18) or two (OR, 0.58; 95% CI, 0.35-0.95) G alleles, a
      known higher producer of the anti-inflammatory cytokine IL-10, was associated
      with lower risk of colorectal cancer (p trend = 0.03). Statistically significant
      associations with colorectal cancer were observed for three tagSNPs in IL10
      (rs1800890, rs3024496, rs3024498) and one common haplotype, but these
      associations were due to high linkage disequilibrium with IL10-1082. Two CRP
      haplotypes (global p = 0.04) and TLR4 tagSNPs (rs7873784, rs11536891), but not
      TLR4 haplotypes, were associated with colorectal cancer. CONCLUSIONS: Our study
      suggests that polymorphisms in IL10, and also possibly in CRP and other genes
      related to immune response or obesity may be associated with colorectal cancer.

PMID- 19760028
TI  - Family history of cancer and risk of breast cancer in the Black Women's Health
      Study.
AB  - INTRODUCTION: Relatively little research has been conducted on familial breast
      cancer in African American women. METHODS: Data from the Black Women's Health
      Study, a prospective cohort study of African American women, were used to assess
      breast cancer risk in relation to family history of cancer. Since 1995,
      participants have completed biennial postal questionnaires on health status, risk
      factors, and family history of cancer. Cox proportional hazards analyses were
      used to calculate incidence rate ratios (IRRs) and 95% confidence intervals (CI)
      for family history of breast and other types of cancer. RESULTS: Among 57,364
      participants who were cancer-free at baseline, 1,306 incident breast cancer cases
      occurred during 12 years of follow-up. The IRR for a first-degree family history
      of breast cancer relative to no family history was 1.78 (95% CI 1.55-2.06). IRRs
      varied by the age at diagnosis, from 1.60 (>or=age 55) to 2.76 (<age 35). Results
      were consistent across subtypes of breast tumor defined by estrogen and
      progesterone receptor status. Breast cancer risk was also associated with family
      history of colon cancer (IRR 1.35, 95% CI 1.12-1.63) and possibly with family
      history of leukemia (IRR 1.42, 95% CI 0.82-2.46). CONCLUSIONS: These findings
      indicate a strong familial relationship for breast cancer in African American
      women. The associations with family history of colon cancer and leukemia warrant
      further investigation.

PMID- 19760029
TI  - Pancreatitis and pancreatic cancer in two large pooled case-control studies.
AB  - OBJECTIVE: The association between duration of pancreatitis and pancreatic cancer
      has not been well characterized in large population-based studies. We conducted
      detailed analyses to determine the association between pancreatitis onset and
      pancreatic cancer risk. METHODS: Data from two case-control studies of pancreatic
      cancer (n = 4515) in the San Francisco Bay Area and the M.D. Anderson Cancer
      Center were pooled for analysis (1,663 cases, 2,852 frequency-matched controls).
      Adjusted odds ratios (OR) were estimated using a random-effects model. Results In
      the pooled multivariable model, history of pancreatitis was associated with a 7.2
      fold increased risk estimate for pancreatic cancer [95% confidence interval (CI):
      4.0, 13]. The risk estimate was nearly 10-fold in participants aged <55 years (OR
      = 9.9, 95% CI: 3.5, 28). A shorter temporal history of pancreatitis was more
      closely associated with pancreatic cancer than was a longer temporal history: <3
      years (OR = 29, 95% CI: 12, 71), 3-10 years (OR = 2.6, 95% CI: 1.5, 5.6), and >10
      years (OR = 1.8, 95% CI: 0.7, 4.5, p trend < 0.001). CONCLUSION: A short temporal
      history of pancreatitis was highly associated with pancreatic cancer, suggesting
      that pancreatitis may be an early manifestation of pancreatic cancer in some
      individuals. Pancreatic cancer should be considered in the differential diagnosis
      of individuals with an episode of pancreatitis.

PMID- 19760030
TI  - Applicability of the Gail model for breast cancer risk assessment in Turkish
      female population and evaluation of breastfeeding as a risk factor.
AB  - The Gail model is considered the best available means for estimating risk of
      breast cancer development, but it has not yet been applied systematically and
      validated in Turkish female population. This study was designed to evaluate the
      performance of the Gail model for Turkish female population. Additionally
      duration of breastfeeding was examined as a possible risk factor. Our analysis
      included 650 patients with invasive breast carcinoma (group 1) and 640 women with
      negative results who had undergone a screening mammography on visiting a mammary
      care unit (group 2). Two groups were compared with regard to individual risk
      factors included in the Gail model and also duration of breastfeeding. The Gail
      model was used to predict 5-year risk for each woman. Age and first live birth >
      or =30 years were associated with an increased relative risk for breast cancer
      development. Age at menarche, previous breast biopsy, atypical hyperplasia, and
      number of first degree relatives with breast cancer were found to be non
      significant. The Gail model showed 13.3% sensitivity and 92% specificity in
      estimating the risk of breast cancer development in Turkish women. Positive
      predictive value was 63%, negative predictive value was 51.9%, and validity index
      was 53.1%. Duration of breastfeeding was significantly longer in group 1 than 2
      (median 17 vs. 13 months). The proportion of parous women with no breastfed was
      higher in group 1 than 2. The currently used Gail model does not seem to be an
      appropriate breast cancer risk assessment tool for Turkish female population.

PMID- 19760032
TI  - Unfavourable clinicopathologic features and low response rate to systemic
      adjuvant therapy: results with regard to poor survival in young Chinese breast
      cancer patients.
AB  - The prognostic factors of young breast cancer patients (BCPs) are still
      controversial. This study is aimed at evaluating the prognosis of young BCPs by
      characteristics and treatment response. We analysed the data on 2,593 operable
      BCPs age <or=50 years who were treated in the Cancer Hospital of Fudan
      University, Shanghai, China between 1990 and 2004. The overall survival and
      recurrence/metastasis-free survival were compared. In the study, 782 patients
      (30.2%) were <or=40 years, and 1,811 (69.8%) were 41-50 years old at their
      primary diagnosis. BCPs <or=40 years presented more unfavourable features than
      the 41-50 years BCPs (P < 0.05). They were more likely to experience death (P <
      0.001) and recurrence/metastasis events (P < 0.001) even when they underwent the
      same adjuvant therapy in parallel with their counterparts (P < 0.05). In a
      multivariate analysis, age was an independent predictive factor for RFS (HR =
      0.26, 95% CI = 0.44-0.89, P = 0.009) but not for OS (P > 0.05). Higher TNM stage
      and chemotherapy, but not HER2/neu over-expression, were predictive factors for
      young Chinese BCPs. The characteristics of breast cancer are more aggressive in
      young Chinese BCPs. Their prognostic factors are obviously different from those
      of the elder group. Current therapy was not as effective for them.

PMID- 19760033
TI  - The complete family of epidermal growth factor receptors and their ligands are co
      ordinately expressed in breast cancer.
AB  - The levels of expression of the four receptors and eleven ligands composing the
      epidermal growth factor family were measured using immunohistochemical staining
      in one hundred cases of breast cancer. All of the family were expressed to some
      degree in some cases; however, individual cases showed a very wide range of
      expression of the family from essentially none to all the factors at high levels.
      The highest aggregate level of expression of a receptor was HER2 followed by
      HER1, then HER3, then HER4. The ligands (including two splice variants of the
      NRG1 and NRG2 genes) broadly fell into three groups, those with the highest
      aggregate expression were Epigen, Epiregulin, Neuregulin 1alpha, Neuregulin
      2alpha, Neuregulin 2beta, Neuregulin 4 and TGFalpha, moderate expression was seen
      with EGF, Neuregulin 1beta and Neuregulin 3, and relatively low levels of
      expression were seen of HB-EGF, Betacellulin and Amphiregulin. Statistical
      analysis using Spearman's Rank Correlation showed a positive correlation of
      expression between each of the factors. Analysing the data using the Cox
      Proportional Hazards model showed that, in this dataset, the most powerful
      predictors of relapse free interval and overall survival were the combined
      measurement of only Epigen and Neuregulin 4.

PMID- 19760034
TI  - A dose- and time-controllable syngeneic animal model of breast cancer
      microcalcification.
AB  - The development of novel diagnostic agents for the detection of breast cancer
      microcalcifications requires a reliable animal model. Based on previous work from
      our group, we hypothesized that a single systemic injection of recombinant bone
      morphogenetic protein-2 (rBMP-2) could be used to create such a model. The cDNA
      encoding mature human BMP-2 was expressed in BL21(DE3) bacteria, purified to
      homogeneity, and refolded as a dimer. Bioactivity was confirmed using a C2C12
      alkaline phosphatase assay. rBMP-2 was radiolabeled with (99m)Tc, and its
      biodistribution and clearance were quantified after both intravenous (IV) and
      intraperitoneal (IP) injection. Fischer 344 rats bearing syngeneic R3230 breast
      tumors received a single intraperitoneal injection of rBMP-2 at a specified dose.
      Tumor microcalcification was quantified over time using micro-single photon
      emission computed tomography (SPECT) and microcomputed tomography (CT). rBMP-2
      could be expressed in E. coli at high levels, isolated at >95% purity, and
      refolded to a bioactive dimer. Beta-phase half-life was 30.5 min after IV
      administration and 47.6 min after IP administration. Renal excretion was the
      primary mode of clearance. A single IP injection of >or=50 microg rBMP-2 when
      tumors were not yet palpable resulted in dose-dependent microcalcification in 8
      of 8 R3230 tumors. No calcification was found in control tumors or in normal
      tissues and organs of animals injected with rBMP-2. Tumor calcification increased
      progressively between weeks 2 and 4 post-rBMP-2 injection. A single IP injection
      of rBMP-2 in rats bearing a syngeneic breast cancer will produce dose-dependent
      and time-dependent microcalcifications. This animal model lays the foundation for
      the development of novel diagnostic radiotracers for breast cancer.

PMID- 19760035
TI  - The efficacy of acupoint stimulation for the management of therapy-related
      adverse events in patients with breast cancer: a systematic review.
AB  - The aim of the present study was to scrutinize the evidence on the use of
      acupoint stimulation for managing therapy-related adverse events in breast
      cancer. A comprehensive search was conducted on eight English and Chinese
      databases to identify clinical trials designed to examine the efficacy of
      acupressure, acupuncture, or acupoint stimulation (APS) for the management of
      adverse events due to treatments of breast cancer. Methodological quality of the
      trials was assessed using a modified Jadad scale. Using pre-determined keywords,
      843 possibly relevant titles were identified. Eventually 26 papers, 18 in English
      and eight in Chinese, satisfied the inclusion criteria and entered the quality
      assessment stage. The 26 articles were published between 1999 and 2008. They
      assessed the application of acupoint stimulation on six disparate conditions
      related to anticancer therapies including vasomotor syndrome, chemotherapy
      induced nausea and vomiting, lymphedema, post-operation pain, aromatase
      inhibitors-related joint pain and leukopenia. Modalities of acupoint stimulation
      used included traditional acupuncture, acupressure, electroacupuncture, and the
      use of magnetic device on acupuncture points. Overall, 23 trials (88%) reported
      positive outcomes on at least one of the conditions examined. However, only nine
      trials (35%) were of high quality; they had a modified Jadad score of 3 or above.
      Three high quality trials revealed that acupoint stimulation on P6 (NeiGuang) was
      beneficial to chemotherapy-induced nausea and vomiting. For other adverse events,
      the quality of many of the trials identified was poor; no conclusive remarks can
      be made. Very few minor adverse events were observed, and only in five trials.
      APS, in particular acupressure on the P6 acupoint, appears beneficial in the
      management of chemotherapy-induced nausea and vomiting, especially in the acute
      phase. More well-designed trials using rigorous methodology are required to
      evaluate the effectiveness of acupoint stimulation interventions on managing
      other distress symptoms.

PMID- 19760036
TI  - Potentially functional polymorphisms in ESR1 and breast cancer risk: a meta
      analysis.
AB  - Estrogen exposure is a central risk factor in the development of breast cancer.
      Estrogen receptor alpha (coded by ESR1) is the key mediator of estrogen response
      in mammary tissue. Genetic changes altering the expression of ESR1 is likely to
      affect breast cancer susceptibility. Since the identification of several
      potentially functional polymorphisms in ESR1 (rs2234693, rs9340799, rs1801132,
      rs3798577, rs2228480), molecular epidemiological studies were conducted in recent
      years to evaluate the association between polymorphisms and breast cancer risk in
      diverse populations. However, the results remain conflicting rather than
      conclusive. This current analysis on 10,300 breast cancer cases and 16,620
      controls on rs2234693 showed a borderline significant decreased breast cancer
      risk for CC and CC/CT carriers (CC vs. TT: OR, 0.92, 95% CI, 0.86-0.99; CC/CT vs.
      TT: OR, 0.95, 95% CI, 0.89-1.00). Variant genotypes of the rs1801132 polymorphism
      were also associated with a decreased breast cancer risk in a dominant model in
      5,649 cases and 6,856 controls (GG/GC vs. CC: OR, 0.92, 95% CI, 0.85-0.99). These
      results suggest that potentially functional ESR1 polymorphisms may play a low
      penetrance role in breast cancer susceptibility. SNPs rs9340799, rs3798577,
      rs2228480, and rs2077647 in ESR1 were not causative SNPs. SNPs rs2747648,
      rs1062577, and rs3020314 were recommended in further association studies and
      functional evaluations.

PMID- 19760037
TI  - Polymorphisms in the UBC9 and PIAS3 genes of the SUMO-conjugating system and
      breast cancer risk.
AB  - SUMOylation consists in the covalent conjugation of small ubiquitin-related
      modifiers to target proteins. SUMOylation participates in processes that are
      tightly linked to tumorigenesis, and genetic variability in the SUMO-conjugating
      system may influence the development of breast cancer. We recently reported that
      variation in the UBC9 gene encoding the SUMO-conjugating enzyme may affect the
      grade of breast tumors. Following comprehensive in silico analyses for detection
      of putative functional polymorphisms in 14 genes of the SUMO system, we selected
      one coding SNP in PIAS3 and seven tag SNPs in UBC9 for association analyses.
      Results were based on 1,021 cases, and 1,015 matched controls from the population
      based GENICA study. Odds ratios (OR) and 95% confidence intervals (CI) were
      estimated by conditional logistic regression. To explore the association with
      polymorphisms closely linked to the genotyped variants, multiple imputation based
      on HapMap data was applied. The study revealed associations of four UBC9
      polymorphisms with risk of grade 1 tumors. Comparison of genotype and haplotype
      models indicated that the best representation of risk solely relied on rs7187167
      under dominant penetrance. Women carrying the rare allele showed an increased
      risk of grade 1 tumors compared with common homozygotes (OR 1.87, 95% CI 1.18
      2.95). This effect appeared to be stronger in women with a family history of
      breast or ovarian cancer. Imputation of polymorphisms in a 300-kb region around
      the genotyped polymorphisms identified no variants with stronger associations.
      Our findings suggest that genetic variation in UBC9 may affect the risk of grade
      1 breast tumors.

PMID- 19760038
TI  - In primary breast cancer the mitotic activity yields similar prognostic
      information as the histological grade: a study with long-term follow-up.
AB  - We evaluated with long-term follow-up, the prognostic value of the mitotic
      activity index (MAI) and the volume corrected mitotic index (M/V-index) compared
      with that of the histological grade in breast cancer patients not treated with
      adjuvant systemic therapy. Of 739 consecutive patients living in the city of
      Nijmegen, the Netherlands, 477 patients with primary unilateral breast cancer
      were not treated with adjuvant systemic therapy and eligible for the study. In
      multivariate survival analyses the MAI and M/V-index showed similar hazard ratios
      (HRs) compared to HRs of histological grade for overall survival (OS) (HR: 1.45,
      1.48, and grade II versus grade I (GII/GI) 1.34, grade III versus grade I
      (GIII/GI) 1.53, respectively) and for breast cancer specific survival (BCSS) (HR:
      1.27, 1.57, and (GII/GI) 1.57 (GIII/GI) 2.32, respectively). Other independent
      prognostic variables for OS and BCSS were age at diagnosis, tumour size, and
      number of positive lymph nodes. In the present study with long term follow-up, we
      compared the prognostic value of mitotic activity with that of histological grade
      and found no advantage for the mitotic activity in predicting either BCSS or OS
      and concluded that histological grade and the mitotic activity were equally
      informative in predicting patient outcome. As histological grade is a well
      established and widely used prognosticator we do not have arguments to replace
      the histological grade by the mitotic indices MAI or M/V-index.

PMID- 19760039
TI  - Does pre-operative breast magnetic resonance imaging in addition  to mammography
      and breast ultrasonography change  the operative management of breast carcinoma?
AB  - Magnetic resonance imaging (MRI) has been used for the local staging of breast
      cancer, especially to determine the extent of multiple lesions and to identify
      occult malignancies. The aim of this study was to evaluate the effect of pre
      operative MRI on the surgical treatment of breast cancer. Between January 2006
      and May 2007, 535 newly diagnosed breast cancer patients who planned to undergo
      breast conserving surgery had clinical examinations, bilateral mammography,
      breast ultrasonography, and breast MRI. The radiologic findings and
      clinicopathologic data were reviewed retrospectively. Ninety-eight (18.3%)
      patients had additional lesions, shown as suspicious lesions on breast MRI, but
      not detected with conventional methods. Eighty-four (15.7%) of these patients had
      a change in surgical treatment plans based on the MRI results. Forty-seven (8.8%)
      of the 84 patients had additional malignancies;the other 37 patients (6.9%) had
      benign lesions. The positive predictive value for MRI-based surgery was 56.0% (47
      of 84 patients). During the period of study, the use of pre-operative MRI was
      increased with time (OR 1.20; 95% CI 1.16-1.23; P < 0.001), but the mastectomy
      rate did not change significantly (OR 0.98; 95% CI 0.95-1.00; P = 0.059).
      Multiple factors were analyzed to identify the patients more likely to undergo
      appropriate and complete surgery based on the additional findings of the pre
      operative MRI, but the results were not statistically significant. This research
      suggests that a pre-operative MRI can potentially lower the rate of incompletely
      excised malignancies by identifying additional occult cancer prior to surgery and
      does not lead to an increase in the mastectomy rate; however, because some benign
      lesions are indistinguishable from suspicious or malignant lesions, excessive
      surgical procedures are unnecessarily performed in a significant portion of
      patients. In the future, the criteria for the use of MRI in local staging of
      breast cancer should be established.

PMID- 19760040
TI  - GSTT1 and GSTP1 polymorphisms and breast cancer risk: a meta-analysis.
AB  - Cytosolic glutathione S-transferase comprises multiple isoenzymes; studies have
      principally examined mu-1 (GSTM1: null/present), theta-1 (GSTT1: null/present)
      and pi-1 (GSTP1 Ile105Val) gene polymorphisms concerning breast cancer risk.
      Regarding GSTT1 and GSTP1 polymorphisms, studies remain controversial and no
      recent meta-analysis has appeared. This meta-analysis aims to examine whether
      GSTT1 and GSTP1 polymorphisms are associated with breast cancer risk. Separate
      analyses were performed on Chinese and non-Chinese populations, in an attempt to
      investigate race-specific effects. Eligible articles were identified by a search
      of MEDLINE bibliographic database for the period up to August 2009. Regarding
      GSTT1 null/present genotype, 41 case-control studies were eligible (16,589 breast
      cancer cases and 19,995 controls); 30 case-control studies were eligible for
      GSTP1 Ile105Val (16,908 cases and 20,016 controls). Pooled odds ratios (ORs) were
      appropriately derived from fixed-effects or random-effects models. At the overall
      analysis, the null GSTT1 genotype was associated with elevated breast cancer risk
      (pooled OR = 1.114, 95% CI: 1.035-1.199, random effects). However, the
      association seemed confined to non-Chinese populations (33 studies, pooled OR =
      1.128, 95% CI: 1.042-1.221, random effects), given that the association was not
      significant in the subset of Chinese studies (eight studies, pooled OR = 1.061,
      95% CI: 0.875-1.286, random effects). Regarding GSTP1 Ile105Val, no statistically
      significant associations were detected in non-Chinese populations (25 studies).
      On the other hand, the GG genotype was associated with increased breast cancer
      risk in Chinese populations (five studies, pooled OR = 1.297, 95% CI: 1.023
      1.645, fixed effects); accordingly, the recessive model yielded statistically
      significant results (pooled OR = 1.273, 95% CI: 1.006-1.610, fixed effects). In
      conclusion, polymorphisms of both GSTT1 and GSTP1 genes seem associated with
      elevated breast cancer risk in a race-specific manner. Given the small number of
      Chinese studies, the finding on GSTP1 Ile105Val merits further investigation.

PMID- 19760041
TI  - Eligible and not eligible studies in the recent meta-analysis about p53
      polymorphism and breast cancer risk.

PMID- 19760042
TI  - Decreased paraoxonase activity in critically ill patients with sepsis.
AB  - Paraoxonase 1 is believed to play a role in preventing lipid oxidation and, thus,
      limiting production of proinflammatory mediators. Systemic inflammatory response
      in sepsis increases oxidative stress and decreases high-density lipoprotein (HDL)
      concentrations. The objective of this study was to investigate serum paraoxonase
      1 activities in critically ill patients with sepsis and after recovery. Serum
      paraoxonase 1 arylesterase/paraoxonase activities, concentration of total
      cholesterol, HDL cholesterol (HDL-C) and serum C-reactive protein (CRP) in septic
      patients of a medical intensive care unit (n = 30) and age/sex-matched outpatient
      controls without sepsis (n = 30) were analyzed. Paired convalescent samples were
      also taken 1 week after recovery (n = 11). In septic patients, both arylesterase
      (88.3 +/- 36.5 vs. 162.1 +/- 44.8 kU/l, P < 0.001) and paraoxonase (75.2 +/- 50.0
      vs. 125.2 +/- 69.4 U/l, P < 0.01) paraoxonase 1 activities decreased as compared
      to controls. Both activities normalized after recovery. Negative correlation was
      found between CRP and both arylesterase (r = -0.676, P < 0.001) and paraoxonase
      (r = -0.401, P < 0.01) as well as positive correlation between HDL-C and both
      arylesterase (r = 0.585, P < 0.001) and paraoxonase (r = 0.405, P < 0.01)
      paraoxonase 1 activities. The decreased activity of paraoxonase 1 in negative
      correlation with CRP offers a potentially useful marker of sepsis progress and
      recovery in critically ill patients.

PMID- 19760043
TI  - SUNCT syndrome or first division trigeminal neuralgia associated with cerebellar
      hypoplasia.
AB  - Short-lasting unilateral neuralgiform headache (SUNCT) and first division
      trigeminal neuralgia (TN) are rare and very similar periorbital unilateral pain
      syndromes. Few cases of SUNCT are associated with posterior skull lesions. We
      describe a 54-year-old man with symptoms compatible with both the previous
      painful syndromes, associated with a small posterior skull and a cerebellar
      hypoplasia. The short height and the reported bone fractures could be compatible
      with a mild form of osteogenesis imperfecta, previously described in one case
      associated with SUNCT. However, a hypoplastic posterior cranial fossa
      characterizes also Chiari I malformation. The difficult differential diagnosis
      between SUNCT and TN and their relation with posterior skull malformations is
      debated.

PMID- 19760044
TI  - Utility of intraoperative PTH for primary hyperparathyroidism due to multigland
      disease.
AB  - BACKGROUND: Surgical resection is the only curative therapy for patients with
      primary hyperparathyroidism (1HPT). Although cure rates of parathyroidectomy are
      generally high, failure is most often due to unrecognized multigland disease
      (MGD), which compromises 15-20% of patients with 1HPT. The use of intraoperative
      PTH (ioPTH) monitoring is well established for single-gland disease. Controversy
      remains over the utility of ioPTH in MGD, with concern for false-positive results
      leading to prematurely concluding the operation and leaving behind abnormal
      parathyroid tissue, risking future recurrence. The aim of this study was to
      determine the utility of ioPTH monitoring for MGD. METHODS: Between November 2000
      and March 2008, data were prospectively collected on 755 patients with 1HPT who
      underwent parathyroidectomy. PTH samples were collected pre-incision, and then at
      5, 10, and 15 min after excision of suspected abnormal parathyroid gland(s).
      Surgical cure was defined as a drop of greater than 50% in PTH level. Patients
      were clinically cured if they became normocalcemic postoperatively and remained
      so for 6 months. The data were analyzed to determine how accurately ioPTH
      predicted success or failure of parathyroidectomy. RESULTS: Of the 755 patients,
      163 (21.5%) were found to have MGD on pathology. Intraoperative PTH monitoring
      was used in 161 of these cases. In 146/161 cases (90.7%), the ioPTH level fell by
      at least 50% after removal of all suspected abnormal glands. All of these
      patients (100%) remained normocalcemic postoperatively. In 15/161 cases (9.3%),
      the PTH level did not fall by >50%. For 11/15 cases (73%), patients remained
      hypercalcemic postoperatively or had recurrence. However, in the remaining four
      cases, the patients became normocalcemic postoperatively despite failure of the
      PTH to fall by >50%. In each of these patients, PTH levels fell by 40-50%.
      CONCLUSIONS: ioPTH monitoring accurately predicted success or failure of
      parathyroidectomy in 97.5% (157/161) of patients with MGD. A fall of ioPTH by
      >50% can be used as a highly accurate predictor of cure in patients with MGD.
      Therefore, ioPTH monitoring is a very useful tool in patients with 1HPT and MGD.

PMID- 19760045
TI  - RGS16 is a marker for prognosis in colorectal cancer.
AB  - BACKGROUND: The RGS family, comprising 22 homologues of proteins, plays a role in
      cellular proliferation, differentiation, membrane trafficking, and embryonic
      development through the involvement of the mitogen-activated protein kinase
      signaling pathway. METHODS: In order to demonstrate the importance of RGS16
      expression for the prediction of prognosis of colorectal cancer (CRC), we
      analyzed RGS16 gene expression in 22 human gastrointestinal cell lines and 124
      paired cases of CRC and noncancerous regions. RESULTS: RGS16 was expressed in 17
      human gastrointestinal cancer cell lines examined in this study. RGS16 expression
      was higher in colorectal cancer tissue than in corresponding normal tissue (P <
      0.001) in messenger RNA (mRNA) and protein levels. Patients in the RGS16 high
      expression group showed a poorer overall survival rate than those in the low
      expression group (P < 0.001), indicating that high RGS16 expression was an
      independent prognostic factor. CONCLUSION: The present study suggests that RGS16
      is useful as a predictive marker for patient prognosis of CRC.

PMID- 19760046
TI  - Reduction of postoperative complication rate with the use of early oral feeding
      in gynecologic oncologic patients undergoing a major surgery: a randomized
      controlled trial.
AB  - BACKGROUND: A randomized controlled trial was performed to assess the outcome of
      early oral postoperative feeding (EOF) compared with traditional oral feeding
      (TOF) in gynecologic oncology patients undergoing a complex laparotomy, including
      upper abdominal surgery. METHODS: Patients aged 18-75 years, undergoing an
      elective laparotomy and with a preoperative suspicion of gynecologic malignancy,
      were eligible. Exclusion criteria included infectious conditions, intestinal
      obstruction, severe malnutrition, American Society of Anesthesiologists score C4,
      intestinal resection, and postoperative stay in the intensive care unit lasting
      24 h. Patients allocated to EOF received liquid diet in the first postoperative
      day and then regular diet. Patients received traditional feeding scheme until
      resolution of postoperative ileus to start liquid diet. The primary end-point of
      the trial was length of hospital stay. RESULTS: Between January 1, 2007, and
      November 17, 2007, a total of 143 patients were randomized to receive either EOF
      or TOF. Hospital stay for patients who received EOF (n=71) was 4.7 vs. 5.8 days
      for the TOF group (n=72) (P=0.006). The mean level of postoperative satisfaction
      was significantly higher in the EOF group (82.8 vs. 71.7 mm, P B 0.001). Patients
      who received the TOF scheme had significantly higher overall postoperative
      complications (39 vs. 17% in EOF group, P=0.003) and infective complications (14%
      in TOF group vs. 3% in EOF group, P=0.017). Variables such as nausea and
      vomiting, analgesic and antiemetic requirement as well as level of pain and
      quality of life were not different between groups. CONCLUSIONS: On the basis of
      these findings, the policy of EOF should be used after a complex gynecologic
      oncologic laparotomy.

PMID- 19760047
TI  - Axillary lymph node dissection for sentinel lymph node micrometastases may be
      safely omitted in early-stage breast cancer patients: long-term outcomes of a
      prospective study.
AB  - OBJECTIVES: To evaluate the long-term disease-free and overall survival of
      patients with sentinel lymph node (SLN) micrometastases, in whom a completion
      axillary lymph node dissection (ALND) was systematically omitted. BACKGROUND: The
      use of step sectioning and immunohistochemistry for SLN analysis results in a
      more accurate histopathologic examination and a higher detection rate of
      micrometastases. However, the clinical relevance and therapeutic implications of
      SLN micrometastases remain a matter of debate. METHODS: In this prospective
      study, 236 SLN biopsies were performed in 234 consecutive early-stage breast
      cancer patients (T1, T2 <or= 3 cm, cN0 M0) between 1998 and 2002. The SLN were
      examined by step sectioning and stained with hematoxylin and eosin and
      immunohistochemistry. None of the patients with negative SLN or SLN
      micrometastases (International Union Against Cancer classification, >.2 mm to
      <or=2 mm) underwent a completion ALND or radiation to the axilla. Long-term
      overall and disease-free survivals were compared between patients with negative
      SLN and those with SLN micrometastases by log rank tests. RESULTS: The SLN was
      negative in 55% of patients (123 of 224). SLN micrometastases were detected in 27
      patients (27 of 224, 12%). After a median follow-up of 77 months (range, 24-106
      months), neither locoregional recurrences nor distant metastases occurred in any
      of the 27 patients with SLN micrometastases. There were no statistically
      significant differences for overall (P = .656), locoregional (P = .174), and
      axillary and distant disease-free survival (P = .15) between patients with
      negative SLN and SLN micrometastases. CONCLUSIONS: This analysis of unselected
      patients provides evidence that a completion level I and II ALND may be safely
      omitted in early-stage breast cancer patients with SLN micrometastases.

PMID- 19760048
TI  - Depression in women living with HIV: clinical and psychosocial correlates.
AB  - The number of Brazilian women living with HIV has increased significantly in past
      years, rendering studies of their particular care demands including psychiatric
      issues. This study measures the prevalence of major depression, using the
      Structured Clinical Interview for DSM-IV Axis I Disorders, in a sample of 120
      women living with HIV in treatment at a reference centre in Sao Paulo. Socio
      demographic variables, HIV-related clinical and laboratory data, including CD4+
      cell counts and HIV plasma viral loads, as well as psychosocial features
      (intimate relationships, disclosure of HIV serostatus, partner's serostatus and
      patient's emotional and financial support) were investigated as factors
      potentially associated with depression. The prevalence of major depression at the
      time of evaluation was 25.8% (95% CI 18.2-33.4%). Clinical status (p = 0.002),
      lack of emotional support (p = 0.02), use of antidepressants (p = 0.028) and
      length of time since HIV diagnosis (p = 0.05) were associated with major
      depression in univariate analysis. In multivariate multiple-regression model, HIV
      clinical status, lack of emotional support and higher plasma viral loads were
      associated with depression. Sixty per cent of the women have a major depression
      diagnosis during lifetime. We conclude that major depression is highly prevalent
      among women living with HIV, but it is still underdiagnosed and undertreated.

PMID- 19760049
TI  - "Under My Umbrella": the housing experiences of HIV positive parents who live
      with and care for their children in Ontario.
AB  - Positive Spaces, Healthy Places (PSHP) is the first longitudinal community-based
      research (CBR) initiative in Canada to examine housing stability and its
      relationship to health related quality of life (HRQOL) for people living with of
      HIV/AIDS (PHAs). As part of our mixed method data collection strategy in-depth,
      semi-structured interviews were conducted with 50 PHAs across Ontario to provide
      a deeper understanding of the impact that housing instability has on their mental
      and physical health. Emerging from the qualitative interviews were the unique
      issues and concerns that were reported by parents who live with and care for
      their children. These parents face dire housing, economic and social challenges
      that are associated with significant risks for poor health outcomes. Poor housing
      conditions, unsafe neighborhoods, barriers to supports for themselves and their
      children, HIV related stigma, discrimination, racism, and poverty have been
      identified by these families as being among their most pressing concerns. This
      results in increased stress and anxiety that has a negative impact on the mental
      health of HIV positive parents. In order to more effectively support HIV positive
      parents and their children, health and social service practices and policies must
      respond to the unique challenges that face these families.

PMID- 19760050
TI  - Risk behaviors for HCV- and HIV-seroprevalence among female crack users in Porto
      Alegre, Brazil.
AB  - Several studies have shown a high prevalence of HIV-seropositive status among
      crack users, though most refer to North American populations. Few studies
      evaluate HCV prevalence among female crack users. In addition, there is a
      particular lack of data about risk behaviors and HIV/HCV prevalence in this
      population around the world. In order to ascertain the HIV/HCV serostatus and
      associated risk behaviors for infection of female crack users of Porto Alegre,
      Brazil. A cross-sectional study of a convenience sample of 73 current female
      crack users was conducted. Subjects answered NIDA's Risk Behavior Assessment and
      an AIDS Information Questionnaire. In addition, blood was collected from subjects
      for HIV/HCV tests. The overall prevalence of HIV was 37.0%; HCV seroprevalence
      was 27.7%; of 15.1% the sample was co-infected with HIV and HCV. Four years of
      schooling or fewer (OR 4.72-CI 95%; 1.49-14.99) and having three or more HIV
      tests in one's lifetime (OR 4.26-CI 95% (1.29-14.04)) were associated with HIV
      infection (after multivariate logistic regression). The single greatest risk
      factor for HCV infection was having 4 years of schooling or fewer (OR 4.51-CI
      95%; 1.18-17.27). We found a very high prevalence of HIV and HCV infection among
      female crack users, and low education was the most significant risk factor
      associated with both infections.

PMID- 19760051
TI  - Validation of the Edinburgh Postnatal Depression Scale among women in a high HIV
      prevalence area in urban Zimbabwe.
AB  - Despite the significant burden of common mental disorders (CMD) among women in
      sub Saharan Africa, data on postnatal depression (PND) is very limited,
      especially in settings with a high HIV prevalence. The Edinburgh Postnatal
      Depression Scale (EPDS), a widely used screening test for PND has been validated
      in many countries, but not in Zimbabwe. We assessed the validity of the EPDS
      scale among postpartum women compared with Diagnostic Manual of Mental Disorders
      (DSM-IV) criteria for major depression. Six trained community counselors
      administered the Shona version of the EPDS to a random sample of 210 postpartum
      HIV-infected and uninfected women attending two primary care clinics in
      Chitungwiza. All women were subsequently subjected to mental status examination
      using DSM IV criteria for major depression by 2 psychiatrists, who were blinded
      to the subject's EPDS scores. Data were analyzed using receiver operating
      characteristic (ROC) curve analysis. Of the 210 postpartum mothers enrolled, 64
      (33%) met DSM IV criteria for depression. Using a cut-off score of 11/12 on the
      Shona version of the EPDS for depression, the sensitivity was 88%, and
      specificity was 87%, with a positive predictive value of 74%, a negative
      predictive value of 94%, and an area under the curve of 0.82. Cronbach's alpha
      coefficient for the whole scale was 0.87. CONCLUSION: The Shona version of the
      EPDS is a reliable and valid tool to screen for PND among HIV-infected and un
      infected women in Zimbabwe. Screening for PND should be integrated into routine
      antenatal and postnatal care in areas with high HIV prevalence.

PMID- 19760052
TI  - Prevention of inappropriate ICD shocks in patients with Brugada syndrome.
AB  - BACKGROUND: In Brugada syndrome implantable cardioverter defibrillator (ICD)
      therapy is associated with a high rate of inappropriate therapies, mainly due to
      supraventricular tachyarrhythmias (SVT) (2.7-14.1%/year). Aim of the present
      study was to evaluate a single ventricular fibrillation (VF) detection zone with
      a high cut-off rate with respect to prevention of inappropriate ICD shock due to
      SVT and safety of this programming. METHODS: Sixty-one consecutive patients (mean
      age 42.6 +/- 12.9 years; 41 males) diagnosed with Brugada syndrome and implanted
      with an ICD were included. ICDs were prospectively programmed with a single VF
      detection zone and a cut-off rate of 222 beats/minute (bpm). A maximum of six
      shocks with the maximal shock energy were programmed. The minimal follow-up was 1
      year. RESULTS: During a follow-up of 47.6 +/- 23.1 months seven patients
      (2.91%/year) received appropriate ICD shocks. No patient suffered from syncope or
      died. Five patients (2.07%/year) received inappropriate ICD shocks: four patients
      due to T-wave oversensing and only one patient (0.4%/year) due to SVT (atrial
      fibrillation with a ventricular rate of >222 bpm). CONCLUSIONS: Programming of a
      single, high-rate VF zone in patients with Brugada syndrome and an implanted
      defibrillator is safe. Such programming may be associated with reduced
      inappropriate defibrillator discharges. A single detection zone with a high VF
      cut-off rate can be recommended in patients with Brugada syndrome.

PMID- 19760056
TI  - Bilateral symmetric junctional infarctions of the cerebellum: a case report.
AB  - The advances in neuroimaging have improved clinicoanatomic correlations in
      patients with stroke. Junctional infarct is a distinct term, used to describe
      border zone infarcts of the posterior fossa. We presented computed tomography
      (CT) and magnetic resonance imaging (MRI) findings in a rare case of bilateral
      symmetrical junctional infarcts between the superior cerebellar artery (SCA) and
      posterior inferior cerebellar artery (PICA) territories. In addition to precise
      knowledge of arterial territories required to achieve accurate localization of
      ischemic lesions on CT and MRI, the radiologist must also be aware of radiologic
      features and geographic territories of cerebellar arteries and their junctional
      infarctions.

PMID- 19760057
TI  - Fine-tuning immune surveillance by fever-range thermal stress.
AB  - An effectively orchestrated immune response to infection and disease depends on
      efficient trafficking of lymphocytes across vascular beds at distinct tissue
      sites. Local inflammation and systemic fever increase immune surveillance to
      immune-relevant sites throughout the body. During the initiation phase of
      inflammation, this tightly regulated process improves leukocyte trafficking to
      the secondary lymphoid organs where they undergo activation and expansion in
      response to cognate antigen. In the resolution phase following the clearance of
      the invading pathogen, lymphocyte entry is rapidly returned to baseline
      conditions. Specialized blood vessels termed high endothelial venules (HEVs) have
      emerged as critical 'hotspots' controlling the rate of lymphocyte entry into
      lymphoid organs during both phases of inflammation. In this review, we will
      examine the remarkably tight regulation of lymphocyte trafficking across HEVs
      conferred by inflammatory cues associated with the thermal element of fever.
      These studies have revealed a novel role for interleukin-6 (IL-6) trans-signaling
      in eliciting systemic effects on lymphocyte trafficking patterns to fine-tune
      immune surveillance.

PMID- 19760058
TI  - Cloning of a heat-stable chitin deacetylase gene from Aspergillus nidulans and
      its functional expression in Escherichia coli.
AB  - A gene encoding chitin deacetylase was cloned by polymerase chain reaction from
      Aspergillus nidulans. Sequencing result showed 40% homology to the corresponding
      gene from Colletotrichum lindemuthianum. The complete gene contains an open
      reading frame of 747 nucleotides encoding a sequence of 249 amino acid residues.
      The chitin deacetylase gene was subcloned into a pET28a expression vector and
      expressed in Escherichia coli BL21 and then purified by metal affinity
      chromatography using a His-bind column. The purified chitin deacetylase
      demonstrated an activity of 0.77 U ml(-1) for the glycol chitin substrates, and
      its specific activity was 4.17 U mg(-1) for it. The optimal temperature and pH of
      the purified enzyme were 50 degrees C and 8.0, respectively. When glycol chitin
      was used as the substrate, K (m) was 4.92 mg ml(-1), and K (cat) showed 6.25 s(
      1), thus the ratio of K (cat) and K (m) was 1.27 ml s(-1) mg(-1). The activity of
      chitin deacetylase was affected by a range of metal ions and
      ethylenediaminetetraacetic acid.

PMID- 19760059
TI  - Collagen cross-links as a determinant of bone quality: a possible explanation for
      bone fragility in aging, osteoporosis, and diabetes mellitus.
AB  - Collagen cross-linking, a major post-translational modification of collagen,
      plays important roles in the biological and biomechanical features of bone.
      Collagen cross-links can be divided into lysyl hydroxylase and lysyloxidase
      mediated enzymatic immature divalent cross-links,mature trivalent pyridinoline
      and pyrrole cross-links, and glycation- or oxidation-induced non-enzymatic cross
      links(advanced glycation end products) such as glucosepane and pentosidine. These
      types of cross-links differ in the mechanism of formation and in function.
      Material properties of newly synthesized collagen matrix may differ in tissue
      maturity and senescence from older matrix in terms of crosslink formation.
      Additionally, newly synthesized matrix in osteoporotic patients or diabetic
      patients may not necessarily be as well-made as age-matched healthy subjects.
      Data have accumulated that collagen cross-link formation affects not only the
      mineralization process but also microdamage formation. Consequently, collagen
      cross-linking is thought to affect the mechanical properties of bone.
      Furthermore,recent basic and clinical investigations of collagen cross-links seem
      to face a new era. For instance, serum or urine pentosidine levels are now being
      used to estimate future fracture risk in osteoporosis and diabetes. In this
      review, we describe age-related changes in collagen cross-links in bone and
      abnormalities of cross-links in osteoporosis and diabetes that have been reported
      in the literature.

PMID- 19760063
TI  - Overview of TNF superfamily: a chest full of potential therapeutic targets.
AB  - Since the discovery of tumor necrosis factor TNFalpha about 25 years ago, TNF
      superfamily has grown to a large family of related proteins consisting of over 20
      members that signal through over 30 receptors. Members of this superfamily have
      wide tissue distribution and play important roles ranging from regulation of the
      normal biological processes such as immune responses, hematopoiesis and
      morphogenesis to their role in tumorigenesis, transplant rejection, septic shock,
      viral replication, bone resorption and autoimmunity. Thus, many approaches to
      harness the potency of TNF superfamily members to treat human diseases have been
      developed. Indeed, TNF and TNF agonistic molecules have been approved for human
      use in the United States and other countries. Many other TNF family members show
      promise for several therapeutic applications, including cancer, infectious
      disease, transplantation and autoimmunity. This chapter will give overview of TNF
      superfamily for exploitation for therapeutic use in humans.

PMID- 19760060
TI  - Adjustment for body mass index and calcitrophic hormone levels improves the
      diagnostic accuracy of the spot urine calcium-to-creatinine ratio.
AB  - SUMMARY: Providers diagnose hypercalciuria using a 24-hour or random urine
      samples. We compared calcium measurements from paired 24-hour and morning urine
      samples; measurements correlated poorly. We developed a formula to correct random
      urine calcium levels. Corrected levels showed excellent agreement with 24-hour
      measurements. Until validation, providers should diagnose hypercalciuria using 24
      hour tests. INTRODUCTION: Hypercalciuria is a risk factor for osteoporosis and
      nephrolithiasis. The 24-hour urine calcium (24HUC) measurement is the gold
      standard to diagnose hypercalciuria, but the spot urine calcium-to-creatinine
      ratio (SUCCR) is more convenient. Although authors claim they are
      interchangeable, we observed inconsistencies during the conduct of a clinical
      trial. Therefore, we systematically evaluated agreement between the tests.
      METHODS: During a 28-inpatient calcium absorption studies in 16 postmenopausal
      women, we simultaneously collected paired fasting morning and 24-hour urine
      specimens. RESULTS: We found moderate correlation between paired SUCCR and 24HUC
      specimens (r = 0.57, p = 0.002), but the SUCCR underestimated 24HUC by a mean of
      83 mg (Bland-Altman). We diagnosed hypercalciuria (24HUC >250 mg) in eight
      specimens using the 24HUC, but only in two specimens using the SUCCR (25%
      sensitivity). We developed a regression model to predict 24HUC using SUCCR,
      parathyroid hormone, body mass index, and 1,25(OH)(2)D. The model improved
      diagnostic sensitivity to 100% and decreased Bland-Altman bias of the SUCCR to
      +0.06 mg/kg/24-hour. CONCLUSIONS: We conclude that the SUCCR underestimates urine
      calcium loss and does not reliably diagnose hypercalciuria. A formula derived
      from multivariate regression incorporating other readily measurable variables
      greatly improved the SUCCR's accuracy. Future studies must verify this correction
      before clinical implementation.

PMID- 19760064
TI  - Therapeutic interventions targeting CD40L (CD154) and CD40: the opportunities and
      challenges.
AB  - CD40 was originally identified as a receptor on B-cells that delivers contact
      dependent T helper signals to B-cells through interaction with CD40 ligand
      (CD40L, CD154). The pivotal role played by CD40-CD40L interaction is illustrated
      by the defects in B-lineage cell development and the altered structures of
      secondary lymphoid tissues in patients and engineered mice deficient in CD40 or
      CD40L. CD40 signaling also provides critical functions in stimulating antigen
      presentation, priming of helper and cytotoxic T-cells and a variety of
      inflammatory reactions. As such, dysregulations in the CD40-CD40L costimulation
      pathway are prominently featured in human diseases ranging from inflammatory
      conditions to systemic autoimmunity and tissue-specific autoimmune diseases.
      Moreover, studies in CD40-expressing cancers have provided convincing evidence
      that the CD40-CD40L pathway regulates survival of neoplastic cells as well as
      presentation of tumor-associated antigens to the immune system. Extensive
      research has been devoted to explore CD40 and CD40L as drug targets. A number of
      anti-CD40L and anti-CD40 antibodies with diverse biological effects are in
      clinical development for treatment of cancer and autoimmune diseases. This
      chapter reviews the role of CD40-CD40L costimulation in disease pathogenesis, the
      characteristics of therapeutic agents targeting this pathway and status of their
      clinical development.

PMID- 19760065
TI  - Targeting TNF for Treatment of Cancer and Autoimmunity.
AB  - Tumor necrosis factor-alpha (TNF-alpha) was first isolated two decades ago as a
      macrophageproduced protein that can effectively kill tumor cells. TNF-alpha is
      also an essential component of the immune system and is required for
      hematopoiesis, for protection from bacterial infection and for immune cell
      mediated cytotoxicity. Extensive research, however, has revealed that TNF-alpha
      is one of the major players in tumor initiation, proliferation, invasion,
      angiogenesis and metastasis. The proinflammatory activities link TNF-alpha with a
      wide variety of autoimmune diseases, including psoriasis, inflammatory bowel
      disease, rheumatoid arthritis, systemic sclerosis, systemic lupus erythematosus,
      multiple sclerosis, diabetes and ankylosing spondylitis. Systemic inhibitors of
      TNF such as etanercept (Enbrel) (a soluble TNF receptor) and infliximab
      (Remicade) and adalimumab (Humira) (anti-TNF antibodies) have been approved for
      the treatment inflammatory bowel disease, psoriasis and rheumatoid arthritis.
      These drugs, however, exhibit severe side effects and are expensive. Hence orally
      active blockers of TNF-alpha that are safe, efficacious and inexpensive are
      urgently needed. Numerous products from fruits, vegetable and traditional
      medicinal plants have been described which can suppress TNF expression and TNF
      signaling but their clinical potential is yet uncertain.

PMID- 19760066
TI  - Targeting of BAFF and APRIL for autoimmunity and oncology.
AB  - BLyS and APRIL are tumor necrosis factor superfamily members shown to be
      important for B-cell development, maturation and survival. Recent data also
      indicate that these cytokines regulate the survival and maintenance of malignant
      B-cells in cancer patients. The key role of BlyS/APRIL in the immune system and
      their potential role in cancers have attracted the attention of basic scientistis
      and biotechnology companies alike. As a result, the pathways regulated by BLYS
      and APRIL have been quickly elevated as attractive targets for antibody-based and
      non-antibody based therapeutics. Exploitation of these pathways has not only
      given us enormous insights into the basic biology of the APRIL/BLyS system but it
      has also identified potential clinical candidates for cancer and autoimmunity. As
      such, multiple biotechnology companies are currently testing various therapeutic
      candidates in the clinic. This chapter will review BLyS and APRIL functions and
      discuss alternative therapeutic approaches to target BLyS and APRIL pathways for
      human malignancies and autoimmunity.

PMID- 19760067
TI  - The role of FasL and Fas in health and disease.
AB  - The FS7-associated cell surface antigen (Fas, also named CD95, APO-1 or TNFRSF6)
      attracted considerable interest in the field of apoptosis research since its
      discovery in 1989. The groups of Shin Yonehara and Peter Krammer were the first
      reporting extensive apoptotic cell death induction upon treating cells with Fas
      specific monoclonal antibodies.1,2 Cloning of Fas3 and its ligand,4,5 FasL (also
      known as CD178, CD95L or TNFSF6), laid the cornerstone in establishing this
      receptor-ligand system as a central regulator of apoptosis in mammals.
      Therapeutic exploitation of FasL-Fas-mediated cytotoxicity was soon an ambitous
      goal and during the last decade numerous strategies have been developed for its
      realization. In this chapter, we will briefly introduce essential general aspects
      of the FasL-Fas system before reviewing its physiological and pathophysiological
      relevance. Finally, FasL-Fas-related therapeutic tools and concepts will be
      addressed.

PMID- 19760068
TI  - OX40 (CD134) and OX40L.
AB  - The interaction between OX40 and OX40L plays an important role in antigen
      specific T-cell expansion and survival. While OX40 is expressed predominantly on
      T-lymphocytes early after antigen activation, OX40L is expressed on activated
      antigen presenting cells and endothelial cells within acute inflammatory
      environments. We discuss here how ligation of OX40 by OX40L leads to enhanced T
      cell survival, along with local inflammatory responses that appear critical for
      both effective T-cell mediated responses and chronic immune pathologies. We
      describe how interventions that block or mimic the OX40-OX40L interaction can be
      applied to treat autoimmune diseases or enhance anti-tumor immune responses. The
      clinically relevant properties of these agents emphasize the importance of this
      particular TNFSF-TNFSF in health and disease.

PMID- 19760069
TI  - Targeting CD70 for human therapeutic use.
AB  - Expression of CD70, a member of the tumor necrosis factor superfamily, is
      restricted to activated T-and B-lymphocytes and mature dendritic cells. Binding
      of CD70 to its receptor, CD27, is important in priming, effector functions,
      differentiation and memory formation of T-cells as well as plasma and memory B
      cell generation. Antibody blockade of CD70-CD27 interaction inhibits the onset of
      experimental autoimmune encephalomyelits and cardiac allograft rejection in mice.
      CD70 has been also detected on hematological tumors and on carcinomas. The highly
      restricted expression pattern of CD70 in normal tissues and its widespread
      expression in various malignancies as well as its potential role in autoimmune
      and inflammatory conditions makes it an attractive target for antibody-based
      therapeutics. This chapter provides an overview of the physiological role of CD70
      CD27 interactions and discusses various approaches to target this pathway for
      therapeutic use in cancers and autoimmunity.

PMID- 19760070
TI  - 4-1BB as a therapeutic target for human disease.
AB  - 4-1BB (CD137) is being thought of as an attractive target for immunotherapy of
      many human immune diseases based on encouraging results with 4-1BB agonistic
      antibody treatment in mouse models of cancer, autoimmune disease, asthma and
      additionally as a means to improve vaccination. In this review, we will summarize
      the results of basic research on 4-1BB and 4-1BB immunotherapy of disease and
      provide some potential mechanistic insights into the many stimulatory and
      regulatory functions of 4-1BB.

PMID- 19760071
TI  - RANK(L) as a key target for controlling bone loss.
AB  - Bone-related diseases, such as osteoporosis or rheumatoid arthritis, affect
      hundreds of millions of people worldwide and pose a tremendous burden to health
      care. By deepening our understanding of the molecular mechanisms of bone
      metabolism and bone turnover, it became possible over the past years to devise
      new and promising strategies for treating such diseases. In particular, three
      molecules, the receptor activator of NF-kappaB(RANK), its ligand RANKL and the
      decoy receptor of RANKL, osteoprotegerin (OPG), attracted the attention of
      scientists and pharmaceutical companies alike. Genetic experiments evolving
      around these molecules established their pivotal role as central regulators of
      osteoclast function. RANK-RANKL signaling not only activates a variety of
      downstream signaling pathways required for osteoclast development, but crosstalk
      with other signaling pathways also fine-tunes bone homeostasis both in normal
      physiology and disease. Consequently, novel drugs specifically targeting RANK
      RANKL and their signaling pathways in osteoclasts are expected to revolutionize
      the treatment of various ailments associated with bone loss, such as arthritis,
      cancer metastases, or osteoporosis.

PMID- 19760072
TI  - Targeting the LIGHT-HVEM pathway.
AB  - Tumor necrosis factor (TNF)-related cytokines function as key communication
      systems between cells of the immune system and mediate inflammation and tissue
      destruction. LIGHT (TNFSF14) is a key component of the communication system that
      controls the responses of T-Cells. LIGHT activates two cell surface receptors,
      the Herpesvirus Entry Mediator (HVEM) and the Lymphotoxin-beta Receptor and is
      inhibited by soluble decoy receptor-3. The LIGHT-HVEM pathway is an important
      cosignaling pathway for T-Cells, whereas LIGHT-LTbetaR modifies the functions of
      dendritic cells and stromal cells by creating tissue microenvironments, which
      promote immune responses. HVEM also binds an Ig superfamily member, B and T
      lymphocyte attenuator (BTLA) that inhibits T-Cell activation. Thus, HVEM serves
      as a molecular switch between stimulatory and inhibitory signaling. Studies in
      humans and experimental animal models reveal that LIGHT contributes to
      inflammation and pathogenesis in mucosal, hepatic, joint and vascular tissues.
      LIGHT is accessible to biologic-based therapeutics, which can be used to target
      this molecule during inflammation-driven diseases.

PMID- 19760073
TI  - GITR: a modulator of immune response and inflammation.
AB  - Glucocorticoid-Induced TNFR-Related (GITR) protein belongs to Tumor Necrosis
      Factor Receptor Superfamily (TNFRSF) and stimulates both the acquired and innate
      immunity. It is expressed in several cells and tissues, including T and Natural
      Killer (NK) cells and is activated by its ligand, GITRL, mainly expressed on
      Antigen Presenting Cells (APCs) and endothelial cells. GITR/GITRL system
      participates in the development of autoimmune/inflammatory responses and graft
      vs. host disease and potentiates response to infection and tumors. These effects
      are due to several concurrent mechanisms including: co-activation of effector T
      cells, inhibition of regulatory T (Treg) cells, NK-cell co-activation, activation
      of macrophages, modulation of DC function and regulation of the extravasation
      process. In this chapter we describe: 1) the main structural features of GITR and
      GITRL, 2) the transduction pathways activated by GITR triggering, 3) the effects
      derived from GITR/GITRL system interaction, considering the interplay between the
      different cells of the immune system. Moreover, the potential use of GITR/GITRL
      modulators in disease treatment is discussed.

PMID- 19760074
TI  - Targeting CD30/CD30L in oncology and autoimmune and inflammatory diseases.
AB  - The transmembrane receptor CD30 (TNFRSF8) and its ligand CD30L (CD153, TNFSF8)
      are members of the tumor necrosis factor (TNF) superfamily and display restricted
      expression in subpopulations of activated T-and B-cells in nonpathologic
      conditions. CD30 expression is upregulated in various hematological malignancies,
      including Reed-Sternberg cells in Hodgkin's disease (HD), anaplastic large cell
      lymphoma (ALCL) and subsets of Non-Hodgkin's lymphomas (NHLs). Increased CD30L
      expression was found on mast cells within HD tumors and preclinical and clinical
      studies with compounds targeting the CD30/ CD30L system in HD and ALCL
      demonstrated therapeutic benefit. Upregulation of CD30 and CD30L is also linked
      to leukocytes in patients with chronic inflammatory diseases, including lupus
      erythematosus, asthma, rheumatoid arthritis and atopic dermatitis (AD).
      Preclinical studies conducted with transgenic mice or biologic compounds
      suggested important regulatory functions of the CD30-CD30L system in various
      aspects of the immune system. Such key regulatory roles and their low expression
      in normal conditions combined with increased expression in malignant tissues
      provided a strong rationale to investigate CD30 and CD30L as therapeutic targets
      in hematologic malignancies, autoimmune and inflammatory diseases. In this
      report, we review the pharmacodynamic effects of specific therapeutic compounds
      targeting the CD30/CD30L system in preclinical- and clinical studies.

PMID- 19760075
TI  - Tumor necrosis factor receptor superfamily member 21: TNFR-related death receptor
      6, DR6.
AB  - TNFRSF21 (death receptor-6, DR6) is an orphan TNF receptor superfamily member and
      belongs to a subgroup of receptors called death receptors. DR6 is expressed
      ubiquitously with high expression in lymphoid organs, heart, brain and pancreas.
      Ectopic expression of DR6 in some cell lines leads to apoptosis and activation of
      the JNK and NF-kappaB pathways. Some tumor cells overexpress DR6, typically in
      conjunction with elevated anti-apoptosis molecules. DR6 deficient mice (DR6(-/-))
      show normal development with no gross pathology in any major organs. In the
      absence of DR6, ligation of the TCR results in enhanced T-cell proliferation,
      activation and skewed Th2 cytokine production. Similarly, B-cells lacking Dr6
      show increased proliferation, cell division and cell survival upon mitogenic
      stimulation (anti-CD40 and LPS) or BCR ligation. As a result, DR6(-/-) mice show
      increased Th2 immune responses to both T-dependent and -independent antigens. All
      those data indicate that DR6 plays an important regulatory role for the
      generation of adaptive immunity. More importantly, DR6(-/-) mice are resistant to
      EAE and allergic airway hypersensitivity, possibly as a result of a deficiency in
      the migration of antigen specific T-cells. Therefore, DR6 is a potential
      therapeutic target for treating inflammatory and autoimmune disease by means of
      biological intervention. In addition, DR6 is highly expressed in many tumor cell
      lines and tumor samples. Interestingly, both of its transcriptional and cell
      surface expression are regulated by the NF-kappaB pathway and metalloproteinase
      in some tumor cell lines, respectively. The role of DR6 as an apoptosis-inducing
      receptor is less clear and perhaps cell type dependent. Therefore, in addition to
      its roles in regulating immune responses, DR6 may also be involved in tumor cell
      survival and immune evasion, which is subject to future investigations.

PMID- 19760076
TI  - TRAIL and other TRAIL receptor agonists as novel cancer therapeutics.
AB  - Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), also known
      as Apo2L, is a member of the TNF superfamily (TNFSF) of cytokines. TRAIL gained
      much attention during the past decade due to the demonstration of its therapeutic
      potential as a tumor-specific apoptosis inducer. TRAIL was identified as a
      protein with high homology to other members of the TNF cytokine family,
      especially to the ligand of Fas/Apo-1 (CD95), CD95L (FasL/APO-1L). TRAIL has been
      shown to induce apoptosis selectively in many tumor cell lines without affecting
      normal cells and tissues, making TRAIL itself as well as agonists of the two
      human receptors of TRAIL which can submit an apoptotic signal, TRAIL-R1 (DR4) and
      TRAIL-R2 (DR5), promising novel biotherapeutics for cancer therapy. An increasing
      number of publications now shows that TRAIL resistance in primary human tumor
      cells will have to be overcome and that sensitization to TRAIL-induced apoptosis
      will be required in many cases. Therefore, it will also be instrumental to
      develop suitable diagnostic tests to identify patients who will benefit from
      TRAIL-based novel anticancer therapeutics and those who will not. Interestingly,
      the first clinical results even in monotherapy with TRAIL as well as various
      agonistic TRAIL receptor-specific antibodies have shown encouraging results. This
      chapter provides a compact overview on the biochemistry of the TRAIL/TRAIL-R
      system, the physiological role of TRAIL and its receptors and the results of
      clinical trials with TRAIL and various TRAIL-R agonistic antibodies.

PMID- 19760077
TI  - Therapeutic Potential of VEGI/TL1A in Autoimmunity and Cancer.
AB  - Vascular endothelial growth inhibitor (VEGI, TNFSF-15) is a novel member of the
      tumor necrosis factor (TNF) superfamily that consists of 174 amino acids and
      exhibits a 20% to 30% sequence homology to other members of the TNF superfamily.
      The VEGI gene is expressed as a transmembrane protein predominantly in
      endothelial cells and induced generally in response to inflammatory stimuli. It
      mediates most of its cellular responses through the interaction of the death
      receptor-3. VEGI activates multiple cell signaling pathways including NF-kappaB,
      STAT3, JNK, p38 MAPK and p42/p44 MAPK. VEGI suppresses the proliferation of
      endothelial cells and tumor cells, induces maturation of dendritic cells and
      induces osteoclastogenesis. How VEGI mediates its effects in autoimmune diseases
      and tumorigenesis is the focus of this review.

PMID- 19760078
TI  - Causes of death in patients with rheumatoid arthritis from 1971 to 1991 with
      special reference to autopsy.
AB  - Rheumatoid arthritis (RA) patients have premature mortality, mostly attributed to
      cardiovascular diseases (CVDs). We studied causes of death (CoDs) and
      contribution of autopsy to them in RA patients treated at a single hospital
      responsible for primary to tertiary RA treatment in Helsinki. In 1971-1991, 960
      RA patients died. The leading CoDs were CVDs, RA, and infections. Over 1971-1991,
      RA and renal deaths declined, but other CoDs showed no change. Autopsied patients
      died more frequently than nonautopsied of coronary heart disease (CHD) and
      gastrointestinal disorders, but less frequently of RA, renal, and endocrinologic
      diseases. Our finding of autopsied patients having CHD more frequently as a CoD
      may indicate that CHD, which may be asymptomatic in RA, may be overlooked during
      lifetime.

PMID- 19760079
TI  - Decreased nanobacteria levels and symptoms of nanobacteria-associated
      interstitial cystitis/painful bladder syndrome after tetracycline treatment.
AB  - INTRODUCTION AND HYPOTHESIS: This study was designed to detect whether
      nanobacteria (NB) reside in urine and bladder tissue samples of patients with
      interstitial cystitis/painful bladder syndrome (IC/PBS) and whether antibiotic
      therapy targeting these organisms is effective in reducing NB levels and IC/PBS
      symptoms. METHODS: Twenty-seven IC/PBS patients underwent cystoscopy. Bladder
      biopsies and urine samples were obtained and cultured for NB, which were
      identified by indirect immunofluorescent staining and transmission electron
      microscopy. RESULTS: Eleven bladder samples showed growth of microbes that were
      identified to be similar to NB. Homologous study of the 16S ribosomal RNA gene
      suggested that the NB could be the pathogen. For enrolled 11 patients, NB levels
      decreased dramatically after tetracycline treatment, and they reported
      significant reduction in the severity of IC/PBS symptoms. CONCLUSIONS: A high
      prevalence of NB was observed in female IC/PBS, and anti-NB treatment effectively
      improved the symptoms, which suggest that NB may cause some cases of IC/PBS.

PMID- 19760081
TI  - Abstracts of the 60th Annual General Meeting of the Irish Cardiac Society.
      October 9-10, 2009. Killarney, County Kerry, Ireland.

PMID- 19760080
TI  - Abstracts of the 34th Annual IUGA (International Urogynecological Association)
      Meeting. Lago di Como, Italy. June 16-20, 2009. Non-discussed poster
      presentations.

PMID- 19760082
TI  - Analysis of spatial-temporal distributions of nitrate-N concentration in
      Shitoukoumen catchment in northeast China.
AB  - This article discusses the generation and migration process of nitrate-N
      pollution in shallow groundwater caused by agricultural nonpoint source pollution
      in the catchment area of Shitoukoumen Reservoir in northeast China. By monitoring
      the shallow groundwater nitrate-N in the low-water period, the normal season, and
      high-flow period in the study area for a year, it was found that the nitrate-N
      concentration in the shallow groundwater of this area had a seasonal variation in
      both spatial and time distribution. In the time distribution, the peak value
      appeared in July, the high-flow period, and the valley value appeared in April,
      the low-water period, and showed a significant correlation with the time
      distribution of fertilization rate and rainfall. In the spatial distribution of
      nitrate-N pollution, when the distribution in shallow groundwater was analyzed
      separately in the three different periods (low-water period, the normal season,
      and high-flow period) and the discipline transference and enrichment of nitrate-N
      pollution in shallow groundwater was determined, this indicated that the region
      in the southeast study area where runoff conditions were better was less
      contaminated, and the region where runoff conditions were poor, as well as the
      region along the river were seriously polluted. The nitrate-N concentration in
      shallow groundwater was distributed mainly along the path of groundwater flow and
      was excreted in the drainage region. This showed that the spatial distribution of
      nitrate-N concentration in the shallow groundwater of the entire region was
      mainly controlled by the groundwater flow system. At the same time, in the middle
      and lower reaches of the study area, the seasonal changes in the recharged
      excreted relationship between groundwater and river caused seasonal differences
      in the spatial distribution of nitrate-N pollution in groundwater. The combined
      effects of the groundwater mobility and the surface river resulted in a poor
      correlation between the groundwater nitrate-N concentration and land-use types.
      Only in the plain area where there was little influence from groundwater runoff
      and the surface river did the groundwater nitrate-N concentration correlate with
      land-use types. The spatial and time distribution of nitrate-N concentration in
      the shallow groundwater of the study area was impacted by agricultural nonpoint
      source pollution, the groundwater flow system, and the surface river and formed a
      concentration response system which uses basins as a unit.

PMID- 19760083
TI  - Comparative analysis of selected hydromorphological assessment methods.
AB  - The European Water Framework Directive 2000/60/EC aims to achieve a good
      ecological status of all surface water bodies in Europe. The definition of the
      ecological status is based on the hydromorphological, hydrochemical, and
      hydrobiological features of water bodies. Numerous methods are applied for the
      purpose of hydromorphological status assessment. This study attempts to compare
      four different methods (EcoRivHab, LAWA Field and Overview Survey, and Rapid
      Bioassessment Protocol) that were applied at two study areas in the Czech part of
      the Elbe River Basin. The selected catchments represent areas with different
      sizes and physical geographic as well as socioeconomic characteristics. All the
      methods applied showed the capacity to identify the natural and even the
      completely changed reaches and provided good information on the river physical
      habitat state. However, they are varied from the viewpoint of the number of
      parameters, number of monitored zones, time and knowledge demands of the
      performed assessment.

PMID- 19760084
TI  - Mercury accumulation in fish species from the Persian Gulf and in human hair from
      fishermen.
AB  - Total and methylmercury concentrations were assessed in muscle and liver of 141
      fish samples from the northern part of the Persian Gulf. All fish samples
      belonged to five different species: grunt, flathead, greasy grouper, tiger-tooth
      croaker, and silver pomfret. In addition, Hg and methylmercury were analyzed in
      scalp hair of 19 fishermen living in the same coastal stations of the Persian
      Gulf and consuming several fish meals a week. Total mercury concentrations in
      fish muscle and liver ranged from 0.01 to 1.35 microg g(-1) w.w. and from 0.02 to
      1.30 microg g(-1) w.w., respectively. In fish muscle, 3% of the Hg concentrations
      were higher than 0.5 microg g(-1) w.w., which corresponds to the maximum
      acceptable WHO level, while 9% were in the range of polluted fish (between 0.3
      and 0.5 microg g(-1) w.w.). The highest mercury concentrations in fish muscle
      were observed in flathead fish at Abadan (average of 0.68 microg g(-1) w.w.).
      Methylmercury fractions in fish muscle and liver amount to 34-99% (median 64%)
      and 24-70% (median 43%), respectively. The mean total Hg concentration in the
      fishermen's scalp hair amounted to 2.9 +/- 2.2 microg g(-1), with 68% in the form
      of methylmercury. Ninety-five percent of the Hg levels in the fishermen's hair
      were below 10 microg g(-1), which is the WHO warning limit. In addition,
      relationships between the mercury levels in hair, on the one hand, and exposure
      related factors such as Hg levels in specific fish species, regional differences,
      and number of fish meals, on the other hand, are discussed. It appears that a
      significant correlation for example exists between Hg levels human hair and fish
      muscle or human hair and age and that mean mercury levels in fish muscle and
      human hair decreased from western (Abadan) to eastern (Abbas port) coastal sites.

PMID- 19760085
TI  - Chemical speciation in waters influenced by lead-zinc metallurgical industry.
AB  - The Lead-Zinc Company region, Kardjali city, Bulgaria, is known to be highly
      polluted with heavy metals from its pyrometallurgical activities. The polluted
      levels and the chemical speciation in surface natural waters in the region as
      well as in the wastewaters of the factory were investigated in January 2008 by
      application of monitoring studies, thermodynamic modeling, and interpretation in
      terms of the "softness-hardness" factor. It was found that the levels of trace
      metals pollution of surface waters were lower than the legislation limits for the
      regions with Pb and Zn production. The wastewater treatment facilities of the
      company were found to operate properly, and the quality of the cleaned waters in
      station Kar4 was comparable to the other surface waters studied (e.g., station
      Kar5). The trace metals were divided into three groups: (1) Fe(3+) and Al(3+),
      being "hard" acids, existed in all the studied waters as hydroxy species
      Fe(OH)2(+), AlOH(2+), and Al(OH)2(+), followed by the phosphate species AlPO4(0)
      and Al(2)(OH)(2)PO4(0); (2) Mn(2+), Zn(2+), and Cd(2+) being "soft" acids with
      crystal field stabilization energy (CFSE) = 0 were present in natural waters
      mainly as free Me(2+) ions. Small concentrations of their MeSO4(0), MeCO3(0)
      species, and of MeCl2(0) (Me = Zn, Cd) species were also calculated. In the
      wastewaters, two more species [Me(SO4)2(2-) and Me(SO4)3(4-)] of the softer Zn
      and Cd metals were also calculated; (3) Cu(2+) and Pb(2+), as "soft" acids with
      CFSE not equal to 0 preferentially coordinated with softer CO3(2-) ions and in
      natural waters existed mainly as MeCO3(0) and PbHCO3(+), followed by free
      Me(2+)ions and MeOH(+). In the wastewaters, MeSO4(0) and Pb(SO4)2(2-) species
      increased at the expense of the free Me(2+) ions. The highest self-cleaning
      capability of natural waters was found with respect to Al and Fe, followed by Mn
      and Cd. The lowest corresponded to Pb, Cu, and Zn.

PMID- 19760086
TI  - Heavy metal uptake and its effect on macronutrients, chlorophyll, protein, and
      peroxidase activity of Paspalum distichum grown on sludge-dosed soils. Heavy
      metal uptake and its effect on P. distichum.
AB  - This study assessed the heavy metal (Cr, Mn, Ni, Cu, Zn, and Pb) uptake and its
      effect on biochemical parameters in Paspalum distichum, a wetland plant. Sludge
      collected from Bhalswa waste dump, New Delhi, was used as heavy metal source and
      dosed in different proportions viz. 20%, 40%, 60%, and 80% to the garden soil.
      The plants accumulated metals mostly in belowground organs. The metal
      accumulation followed the order: Cr>Mn>Cu>Zn>Ni>Pb. The range of heavy metal
      concentration in tissue of belowground organs after 180 days of growth was
      1,778.65-4,288.01 ppm Cr, 828.11-1,360 ppm Mn, 236.52-330.07 ppm Ni, 155.79
      282.35 ppm Cu, 27.05-91.16 ppm Zn, and 27.09-50.87 ppm Pb. The biochemical
      parameters viz. chlorophyll and protein contents and peroxidase (POD) activity
      exhibited no considerable adverse effect indicating the plants' tolerance towards
      heavy metals. The high POD activity and synthesis of new protein bands at high
      sludge-dosed plants were also in support of this fact.

PMID- 19760087
TI  - Positive sampling artifacts in particulate organic carbon measurements in
      roadside environment.
AB  - The positive artifacts in particulate organic carbon measurements in a roadside
      environment were characterized using two filters in tandem. The experiments were
      performed for PM(1.0), PM(2.5), and PM(10) at 24-h interval using a URG sampler,
      followed by organic carbon (OC)/elemental carbon (EC) analysis by the Interagency
      Monitoring of Protected Visual Environments thermal/optical reflectance carbon
      analysis protocol. The OC concentrations, derived from the quartz filter behind a
      front quartz filter, were quite similar for PM(1.0), PM(2.5), and PM(10), ranging
      from 0.6 to 2.7 microg C m(-3) for PM(1.0), from 0.7 to 2.7 microg C m(-3) for
      PM(2.5), and from 1.1 to 2.7 microg C m(-3) for PM(10). They were respectively
      approximately 2.8%, approximately 2.4%, and approximately 1.6% of the particulate
      mass. The most abundant species on the backup quartz filters were OC2 (250
      degrees C) and OC3 (450 degrees C), accounting for approximately 80% of measured
      organic carbon on the backup quartz filters. It indicates the filter artifacts
      are mainly composed of adsorbed semi-volatile organics (below the analysis
      temperature of 450 degrees C) including gaseous and particulate phase; the
      loading of artifacts depends on the nature of vapor and its interaction with
      filter substrate, rather than particle sizes. The uncorrected OC/EC ratios on the
      front quartz filters were approximately 10% higher than the corrected OC/EC
      ratios by positive organic artifacts in winter, and it is approximately 20%
      higher in summer. Another finding is that the separation distance of the front
      and backup filters influence the level of artifacts assessed by the backup
      filter.

PMID- 19760088
TI  - An assessment of macroinvertebrate assemblages in mosquito larval habitats--space
      and diversity relationship.
AB  - The aquatic bodies designated as mosquito larval habitats are diverse in size and
      species composition. The macroinvertebrate predators in these habitats are
      elements that influence the abundance of mosquito species, providing a basis for
      biological control. Assessment of species assemblage in these habitats will
      indicate the possible variations in the resource exploitation and trophic
      interactions and, therefore, can help to frame biological control strategies more
      appropriately. In the present study, the species composition is being
      investigated in five different mosquito larval habitats at a spatial scale. A
      random sample of 80 each of the habitats, grouped as either small or large, was
      analyzed in respect to the macroinvertebrate species assemblage. The species
      composition in the habitats was noted to be an increasing function of habitat
      size (species number = 1.653 + 0.819 habitat size) and, thus, the diversity. The
      relative abundance of the mosquito immatures varied with the habitat, and the
      number of useful predator taxa was higher in the larger habitats. In the smaller
      habitats-plastic and earthen structures and sewage drains, the relative and
      absolute number of mosquito immatures per sampling unit were significantly higher
      than the pond and rice field habitats. This was evident in the cluster analysis
      where the smaller habitats were more related than the larger habitats. The
      principal component analysis on the species diversity yielded four and six
      components, respectively, for the smaller and larger habitats for explaining the
      observed variance of species abundance. The species composition in the habitats
      was consistent with the earlier findings and support that the abundance of
      coexisting macroinvertebrate species regulates the relative load of mosquito
      immatures in the habitats. The findings of this study may be further tested to
      deduce the relative importance of the habitats in terms of the productivity of
      mosquito immatures at a temporal scale.

PMID- 19760089
TI  - Occurrence and distribution of organochlorine pesticides (DDT and HCH) in
      sediments from the middle and lower reaches of the Yellow River, China.
AB  - Sediments used in this study were selected from 23 stations in the middle and
      lower reaches of the Yellow River and its tributaries in November 2005. The
      levels and distribution patterns of selected organochlorine pesticides (OCPs =
      p,p(')-DDT, o,p (')-DDT, p,p(')-DDE, p,p(')-DDD, alpha-, beta-, gamma-, and delta
      HCH) in samples were investigated by analysis of gas chromatography coupled with
      micro-electronic capture detector. Concentration of OCPs in the sediments from
      the Yellow River ranged from 0.05 to 5.03 ng g(-1) (mean, 1.02 ng g(-1)) for
      summation operatorDDT, 0.09-12.89 ng g(-1) (mean, 1.08 ng g(-1)) for summation
      operatorHCH. The concentration distribution of summation operatorDDT and
      summation operatorHCH varied significantly with different sampling station,
      indicating their different contamination sources. Composition analyses
      demonstrated that residues of DDTs in sediments came from the previous inputs of
      organochlorine pesticides, while beta-HCH and gamma-HCH significantly dominated
      in the sediments for HCHs.

PMID- 19760090
TI  - Production of a fungistatic substance by Pseudallescheria boydii isolated from
      soil amended with vegetable tissues and its significance.
AB  - Four fungal isolates that were able to use vegetable tissues for multiplication
      in soil were isolated and identified as Pseudallescheria boydii based on
      morphological characteristics and ITS sequence similarity. When grown in broth
      prepared from the same vegetable tissues used in soil amendment, all these
      isolates of P. boydii produced a substance capable of reducing the disease
      incidence of black leaf spot of spoon cabbage caused by Alternaria brassicicola
      and inhibiting the germination of A. brassicicola conidia. The substance, which
      was fungistatic, was very stable under high temperature and high or low pH value.
      It was soluble in polar solvents and insoluble in non-polar solvents. Molecular
      weight estimation and ion exchange ability tests suggest that the fungistatic
      compound has a molecular weight between 500 and 1,000 and has no charge on its
      molecule. Results from this study suggest the possession of a strong competitive
      saprophytic ability by P. boydii, which in turn may explain the widespread
      occurrence of this human pathogen in soil. Production of a fungistatic substance
      when P. boydii was grown in broth prepared from vegetable tissues suggests the
      importance of antibiotic production in its competitive saprophytic colonization
      of organic matters in soil.

PMID- 19760092
TI  - Foreword: Coping with sex chromosome imbalance.

PMID- 19760091
TI  - Tc-99m sestamibi single photon emission computed tomography for guiding
      percutaneous coronary intervention in patients with multivessel disease: a
      comparison with quantitative coronary angiography and fractional flow reserve.
AB  - To evaluate the accuracy of myocardial perfusion SPECT (MPI) in the detection and
      allocation of vessel specific perfusion defects (PD) using standard distribution
      territories in a routine clinical procedure of patients with multivessel disease
      (MVD). Combined quantitative coronary angiography and fractional flow reserve
      (QCA/FFR) measurements were used as invasive reference standard. 216 vessels in
      72 MVD patients (67 +/- 10 years, 28 female) were investigated using MPI and QCA.
      FFR of 93 vessels with intermediate stenoses was determined. MPI detected
      significant stenoses according to QCA/FFR findings with a sensitivity of 85%.
      However, vessel-based evaluation using standard myocardial distribution
      territories delivered a sensitivity of only 62% (28 MPI+ out of 45 (QCA/FFR)+
      findings), with specificity, PPV and NPV of 90, 62 and 90%. 7/17 false positive
      and 7/17 false negative findings (41%) could be attributed to incorrect
      allocation of reversible PD to their respective coronary arteries. 6/17 (35%)
      perfusion territories were classified as false negative when additional fixed PD
      were present. MPI had reasonable sensitivity for the detection of significant
      coronary artery disease in patients with multivessel disease. However,
      sensitivity decreased markedly, when the significance of each individual stenosis
      was evaluated using standard myocardial supplying territories. In this setting,
      41% of false negative and false positive MPI findings resulted from incorrect
      allocation of reversible perfusion defects to their determining supplying vessel.

PMID- 19760093
TI  - Molecular cloning and mRNA expression of peroxiredoxin gene in black tiger shrimp
      (Penaeus monodon).
AB  - The techniques of homology cloning and anchored PCR were used to clone the
      peroxiredoxin (Prx) gene from black tiger shrimp (Penaeus monodon). The full
      length cDNA of black tiger shrimp Prx (PmPrx) contained a 5' untranslated region
      (UTR) of 51 bp, an ORF (open reading frame) of 582 bp encoding a polypeptide of
      193 amino acids with an estimated molecular mass of 22.15 kDa and a 3' UTR of 948
      bp. Sequence comparison showed that PmPrx shared higher identities with Prx IVs
      than that with other isoforms of Prx, indicating PmPrx was a member of the Prx IV
      family. A quantitative reverse transcriptase Real-Time PCR (qRT-PCR) assay was
      developed to assess the mRNA expression of PmPrx in different tissues and the
      temporal expression of PmPrx in the hepatopancreas challenged by
      lipopolyssacharide (LPS). Higher-level mRNA expression of PmPrx was detected in
      the tissues of hepatopancreas, gonad and heart. The expression of PmPrx in the
      hepatopancreas was up regulated after stimulated by LPS. The results indicated
      that PmPrx was a constitutive and inducible expressed protein and could be
      induced by LPS.

PMID- 19760094
TI  - Sequence analysis of an isolate of minute virus of canines in China reveals the
      closed association with bocavirus.
AB  - In the present study, we have cloned and sequenced the nearly-full-length genome
      of minute virus of canines (MVC), SH26, in China. The genome of MVC, 5,132
      nucleotides (nts) in length, contains three open reading frames (ORFs), which are
      2,325-bp of NS1, 561-bp of NP1 and 2,112-bp of VP1/VP2 encoding three proteins of
      774, 186 and 703 residues, respectively. Predicted amino acids sequence of NS1 of
      MVC has 44% identity with human bocavirus (HBoV) and human boacvirus 2 (HBoV2),
      NP1 has 48 and 45% identity with HBoV and HBoV2, VP1/VP2 has 45 and 46% identity
      with HBoV and HBoV2, respectively. Phylogenetic analysis showed that the present
      Chinese MVC strain was also closely clustered with the previous American and
      Japanese MVC isolates, and MVCs formed a different branch together with bovine
      parvovirus and HBoVs from other parvoviruses classified into Parvovirinae.

PMID- 19760095
TI  - Analysis of genetic diversity in cytoplasmic male sterility, and association of
      mitochondrial genes with petaloid-type cytoplasmic male sterility in tuber
      mustard (Brassica juncea var. tumida Tsen et Lee).
AB  - In our previous study, we bred a stable cytoplasmic male sterility (CMS) line of
      tuber mustard by using distant hybridization and subsequent backcrosses. In this
      CMS plants, all floral organs are normal except the anthers, which are
      transformed into petals or tubular structures. Recently, 2 mitochondrial genes
      atpA and orf220-that are distinctively present in the CMS line of tuber mustard
      were cloned and partially characterized. In our study of genetic diversity
      analysis of CMS, 7 species of Brassica and Raphanus crops, which included 5 CMS
      lines and their respective maintainer lines, were used to compare the
      constitution of protein-coding genes in the mitochondrial genomes. In 4 of the 43
      mitochondrial genes, namely, atpA, orf220, orf256, and orf305/orf324,
      polymorphisms were detected among the tuber mustard CMS line and its maintainer
      line. The results of a cluster analysis indicate that petaloid CMS phenotype of
      tuber mustard is a novel CMS type and is nearer to the nap CMS in Brassica napus
      at the phylogenetic level. The results of individual amplifications of these
      genes indicate the presence of 4 sequence-characterized amplified region (SCAR)
      markers, which enable rapid and reliable identification of this CMS. Expressions
      of the orf220 and orf256 genes were detected only in the CMS line, while
      expression of the orf305 gene was detected in the maintainer line. The different
      expression patterns of different mitochondrial-specific marker genes indicate
      that the quantity of mitochondrial proteins is differentially regulated during
      organ/tissue development in tuber mustard. The results of this study suggest that
      the above mentioned 4 mitochondrial genes are associated with the petaloid CMS
      phenotype in tuber mustard.

PMID- 19760096
TI  - Two novel SNPs in the coding region of the bovine PRDM16 gene and its
      associations with growth traits.
AB  - As a zinc-finger protein, PR domain containing 16 (PRDM16) controls brown fat
      determination by stimulating brown fat-selective genes expression while
      suppressing the expression of genes selective for white fat cells, whose
      mutations were associated with myelodysplastic syndrome (MDS) and leukemogenesis
      in human and murine model of leukemia. To date, no polymorphisms of PRDM16 gene
      in bovine had been reported. Herein, PCR-SSCP and DNA sequencing methods were
      employed to screen the genetic variation within PRDM16 gene in 1031 Chinese
      indigenous bovine. The results revealed two novel silent mutations: XM_001788152:
      m.1641T>C (547aa), 1881G>A (627aa). Hence, we described the PvuII and HaeIII
      forced PCR-RFLP methods for detecting these mutations, respectively. In the
      forced PCR-RFLP analysis with PvuII, the frequencies of bovine PRDM16-C allele
      varied from 0.044 to 0.506 in four Chinese native breeds. In the forced PCR-RFLP
      analysis with HaeIII, the frequencies of bovine PRDM16-G allele were 0.474,
      0.494, 0.576 and 0.906 for Jiaxian (JX), Nanyang (NY), Qinchuan (QC) and Chinese
      Holstein (CH) population. Significant statistical differences between genotypic
      frequencies implied that both of the polymorphic loci were significantly
      associated with cattle breeds by the chi square test (chi2 = 190.058, P < 0.001
      and chi2 = 118.239, P < 0.001 for PvuII; chi2 = 209.842, P < 0.001 and chi2 =
      108.711, P < 0.001 for HaeIII). The associations of the PvuII and HaeIII forced
      PCR-RFLPs of bovine PRDM16 loci with growth traits were analyzed in Nanyang
      breed. The two SNPs were associated with body weight and average daily gain in
      Nanyang aged 12 months, individuals with genotype TT and AA showed significantly
      better body weight (P < 0.05) and average daily gain (P < 0.01) at 12 months,
      respectively.

PMID- 19760097
TI  - Role of aldose reductase in TGF-beta1-induced fibronectin synthesis in human
      mesangial cells.
AB  - Accumulation of glomerular extracellular matrix (ECM) may result in
      glomerulosclerosis. Several lines of evidence indicate a key role for
      transforming growth factor-beta1 (TGF-beta1) in glomerular ECM synthesis and
      degradation, such as fibronectin (FN). Aldose reductase (AR) was proven to be one
      of the TGF-beta1 responsive genes in cultured rat mesangial cells using the SSH
      PCR method and there were positive correlation between the AR and TGF-beta1 in
      our previous studies. So we assumed that AR could regulate FN synthesis. In this
      study, we explored the role of AR in FN production and possible mechanism
      involved. The expression of AR, FN and c-Jun proteins were analyzed by Western
      blot and the activity of activator protein-1 (AP-1) was assessed by
      electrophoretic mobility shift assay (EMSA). Our results showed that AR could
      mediate the TGF-beta1-induced FN production, which may associate with AP-1
      activation.

PMID- 19760098
TI  - Two novel cSNPs of weaver gene in Chinese indigenous goat and their associations
      with milk yield.
AB  - Weaver gene plays an essential physiological role in the function of many organs,
      including brain, heart, kidney and endocrine cells, and also in the regulation of
      insulin secretion by glucose and/or neurotransmitters. Thus, weaver gene is an
      important potential candidate gene effecting on performance traits. The objective
      of this study was to detect the genetic variation of five loci within weaver gene
      by PCR-SSCP, DNA sequencing and forced PCR-RFLP methods in 1,019 Chinese
      indigenous goats. Two novel coding SNPs (XM_598993:m.864G>A; XM_598993:m.1224T>A)
      locating on P3 and P4 loci were identified and detected by MluI and AsuII forced
      PCR-RFLP, respectively. In the MluI analysis, the frequencies of goat MluI-A
      allele in the analyzed populations were 0.226, 0.248, 0.096 and 0.088 for XNSN,
      GZ, SBWC and XJWC, respectively. Genotypic frequencies were found to be
      significantly different in four breeds (chi2 = 75.842, df = 6, P < 0.001); In the
      AsuII analysis, the frequencies of goat AsuII-A allele in the analyzed
      populations were 0.584, 0.441, 0.073 and 0.063 for XNSN, GZ, SBWC and XJWC,
      respectively. Genotypic frequencies were found to be significantly different
      among four breeds (chi2 = 399.464, df = 6, P < 0.001). The frequencies of allele
      MluI-A and AsuII-A in XNSN and GZ populations were significantly higher than
      those of SBWC and XJWC goats. Association analysis with adjusted milk yield in
      the XNSN breed indicated that the animals with AsuII-AA genotype owned
      significantly higher adjusted milk yield than the ones with AsuII-TT genotype in
      the second lactation (P < 0.05). The observation suggested that the allele "AsuII
      A" had the positive effects on adjusted milk yield in the second lactation.

PMID- 19760099
TI  - Expression, purification and characterization of recombinant human interleukin-22
      in Pichia pastoris.
AB  - Interleukin-22 (IL-22) is a member of the IL-10 family. Its potential in clinical
      use has been highlighted for its important roles in promoting antimicrobial
      defense and preventing epithelial damages. Previous studies have reported that IL
      22 can be expressed using prokaryotic systems and purified from inclusion bodies,
      however the recovery rate was poor. To produce functional IL-22 with a high
      yield, human IL-22 was inserted into the eukaryotic expression vector pPICZalphaA
      and transformed into Pichia pastoris. The expression of recombinant human IL-22
      (rhIL-22) was induced by methanol and accounted for about 85% of the total
      secreted proteins. A simple purification strategy was established to purify the
      rhIL-22 from the culture supernatant, yielding 100 mg/l at 90% purity by
      chromatography with a SP Sepharose FF column. Bioactivity analysis showed the
      purified rhIL-22 demonstrated a specific activity that was comparable with the
      commercial one. This study provides a new strategy for large-scale production of
      bioactive IL-22 for use in basic studies and therapeutic applications.

PMID- 19760100
TI  - Milbemectin resistance in Tetranychus urticae (Acari: Tetranychidae): selection,
      stability and cross-resistance to abamectin.
AB  - Studies on artificial laboratory selections with milbemectin, stability of
      milbemectin resistance and possible cross-resistance with abamectin were carried
      out with Tetranychus urticae Koch to provide basic information for a milbemectin
      resistance management program. Selections for resistance and susceptibility to
      milbemectin were performed in a population of T. urticae, collected from a
      commercial chrysanthemum field in the State of Sao Paulo, Brazil. After six
      selections for resistance and five selections for susceptibility, susceptible (S)
      and resistant (R) strains of T. urticae to milbemectin were obtained. The
      resistance ratio (R/S) at the LC(50) reached 409-fold value. The stability of
      milbemectin resistance was also studied under laboratory conditions, using a
      population with initial frequency of 75% of resistant mites. The frequencies of
      milbemectin resistance were evaluated monthly for a period of 7 months. In order
      to observe possible correlation between milbemectin and abamectin resistance, the
      frequencies of abamectin resistance were also evaluated for that population,
      during the same period. The frequency of milbemectin resistance decreased from 75
      to 14.5%, while the percentage of abamectin resistant mites decreased from 57 to
      9.1%, in 7 months. The frequencies of milbemectin and abamectin resistance were
      also evaluated in 25 field populations of T. urticae, collected from several
      crops in the State of Sao Paulo. The frequencies of milbemectin resistance varied
      from 4.1 to 89.5%, and of abamectin, from 7.0 to 90.5%. A positive and
      significant correlation was observed between the frequencies of milbemectin and
      abamectin resistance, indicating positive cross-resistance between these
      acaricides. The results indicate that abamectin should be avoided for managing
      milbemectin resistance in T. urticae. This is the first report on milbemectin
      resistance in T. urticae in Brazil.

PMID- 19760101
TI  - Effectiveness of eriophyid mites for biological control of weedy plants and
      challenges for future research.
AB  - Eriophyid mites have been considered to have a high potential for use as
      classical biological control agents of weeds. We reviewed known examples of the
      use of eriophyid mites to control weedy plants to learn how effective they have
      been. In the past 13 years, since Rosenthal's 1996 review, 13 species have
      undergone some degree of pre-release evaluation (Aceria genistae, A. lantanae,
      Aceria sp. [boneseed leaf buckle mite (BLBM)], A. salsolae, A. sobhiani, A.
      solstitialis, A. tamaricis, A. thalgi, A. thessalonicae, Cecidophyes rouhollahi,
      Floracarus perrepae, Leipothrix dipsacivagus and L. knautiae), but only four (A.
      genistae, Aceria sp. [BLBM], C. rouhollahi and F. perrepae) have been authorized
      for introduction. Prior to this, three species (Aceria chondrillae, A. malherbae
      and Aculus hyperici) were introduced and have become established. Although these
      three species impact the fitness of their host plant, it is not clear how much
      they have contributed to reduction of the population of the target weed. In some
      cases, natural enemies, resistant plant genotypes, and adverse abiotic conditions
      have reduced the ability of eriophyid mites to control target weed populations.
      Some eriophyid mites that are highly coevolved with their host plant may be poor
      prospects for biological control because of host plant resistance or tolerance of
      the plant to the mite. Susceptibility of eriophyids to predators and pathogens
      may also prevent them from achieving population densities necessary to reduce
      host plant populations. Short generation time, high intrinsic rate of increase
      and high mobility by aerial dispersal imply that eriophyids should have rapid
      rates of evolution. This raises concerns that eriophyids may be more likely to
      lose efficacy over time due to coevolution with the target weed or that they may
      be more likely to adapt to nontarget host plants compared to insects, which have
      a longer generation time and slower population growth rate. Critical areas for
      future research include life history, foraging and dispersal behavior, mechanisms
      controlling host plant specificity, and evolutionary stability of eriophyid
      mites. This knowledge is critical for designing and interpreting laboratory and
      field experiments to measure host plant specificity and potential impact on
      target and nontarget plants, which must be known before they can be approved for
      release. One of the more successful examples of an eriophyid mite controlling an
      invasive alien weed is Phyllocoptes fructiphilus, whose impact is primarily due
      to transmission of a virus pathogenic to the target, Rosa multiflora. Neither the
      mite nor the virus originated from the target weed, which suggests that using
      "novel enemies" may sometimes be an effective strategy for using eriophyid mites.

PMID- 19760102
TI  - What's "cool" on eriophyoid mites?
AB  - Fundamental knowledge on the morphology, biology, ecology, and economic
      importance of Eriophyoidea has been exhaustively compiled by Lindquist et al.
      (Eriophyoid mites--their biology, natural enemies and control; Elsevier, 1996).
      Since that time, the number of recognized species and the economic importance of
      the taxon have increased substantially. The aim of this paper is to analyze and
      briefly review new findings from eriophyoid mites' literature after Lindquist et
      al. book, stressing persistent gaps and needs. Much recent attention has been
      given to sampling and detection, taxonomy and systematics, faunistic surveys,
      internal morphology, rearing techniques, biological and ecological aspects,
      biomolecular studies, and virus vectoring. Recommendations are made for
      integrating research and promoting broader dissemination of data among
      specialists and non-specialists.

PMID- 19760103
TI  - Measuring health-related quality of life in population-based studies of coronary
      heart disease: comparing six generic indexes and a disease-specific proxy score.
AB  - PURPOSE: To compare HRQoL differences with CHD in generic indexes and a proxy CVD
      specific score in a nationally representative sample of U.S. adults. METHODS: The
      National Health Measurement Study, a cross-sectional random-digit-dialed
      telephone survey of adults aged 35-89, administered the EQ-5D, QWB-SA, HUI2,
      HUI3, SF-36v2 (yielding PCS, MCS, and SF-6D), and HALex. Analyses compared 3,350
      without CHD (group 1), 265 with CHD not taking chest pain medication (group 2),
      and 218 with CHD currently taking chest pain medication (group 3), with and
      without adjustment for demographic variables and comorbidities. Data on 154
      patients from heart failure clinics were used to construct a proxy score
      utilizing generic items probing CVD symptoms. RESULTS: Mean scores differed
      between CHD groups for all indexes with and without adjustment (P < 0.0001 for
      all except MCS P = 0.018). Unadjusted group 3 versus 1 differences were about
      three times larger than for group 2 versus 1. Standardized differences for the
      proxy score were similar to those for generic indexes, and were about 1.0 for all
      except MCS for group 3 versus 1. CONCLUSIONS: Generic indexes capture differences
      in HRQoL in population-based studies of CHD similarly to a score constructed from
      questions probing CVD-specific symptoms.

PMID- 19760104
TI  - Influences on self-evaluation during a clinical skills programme for nurses.
AB  - Education has moved from teacher to student-centred practices. Increasing
      emphasis is placed on 'life-long' learning in the context of a rapidly changing
      knowledge base. Self-evaluation is seen as one strategy to facilitate student
      centred continuous professional development. The literature, however, suggests
      that learners' ability to self-assess is mixed, and little is known regarding how
      students perform self-assessment. This study focussed on senior nurses
      undertaking a scenario-based clinical skills course. Learners were asked to self
      evaluate several times during the course. This research explored the influences
      on using the self-evaluation exercise. The study drew upon grounded theory
      methodology and was influenced by constructionist and postmodernist theories.
      Three methods of data collection were used: semi-structured interviews,
      observation of supervision sessions and recording of the numerical self
      evaluation ratings. Multiple interviews with students (n = 14) and the
      educational supervisor (n = 1) were conducted. Thematic analysis and data
      collection were conducted iteratively. The study found that feeling confident and
      stating that confidence were not necessarily the same. Feeling confident was
      complex, influenced by changing perceptions of clinical skills and credibility.
      Changing frames of reference were used to judge feelings of confidence. Stating
      confidence appeared to be socially negotiated, influenced by social acceptability
      considerations such as modesty and the need to show progress over time. The
      discourses of empowerment and surveillance were influential and self-evaluation
      is discussed using Foucault's theory of governmentality, illustrating how
      learners can be both empowered and controlled through self-evaluation. Further
      consideration of the socially constructed nature of self-evaluations would
      benefit both educational practice and future research.

PMID- 19760105
TI  - Determinants of DNA yield and purity collected with buccal cell samples.
AB  - Buccal cells are an important source of DNA in epidemiological studies, but
      little is known about factors that influence amount and purity of DNA. We
      assessed these factors in a self-administered buccal cell collection procedure,
      obtained with three cotton swabs. In 2,451 patients DNA yield and in 1,033
      patients DNA purity was assessed. Total DNA yield ranged from 0.08 to 1078.0
      microg (median 54.3 microg; mean 82.2 microg +/- SD 92.6). The median UV 260:280
      ratio, was 1.95. Samples from men yielded significantly more DNA (median 58.7
      microg) than those from women (median 44.2 microg). Diuretic drug users had
      significantly lower purity (median 1.92) compared to other antihypertensive drug
      users (1.95). One technician obtained significantly lower DNA yields. Older age
      was associated with lower DNA purity. In conclusion, DNA yield from buccal swabs
      was higher in men and DNA purity was associated with age and the use of
      diuretics.

PMID- 19760106
TI  - Relative solvation free energies calculated using an ab initio QM/MM-based free
      energy perturbation method: dependence of results on simulation length.
AB  - Molecular dynamics (MD) simulations in conjunction with thermodynamic
      perturbation approach was used to calculate relative solvation free energies of
      five pairs of small molecules, namely; (1) methanol to ethane, (2) acetone to
      acetamide, (3) phenol to benzene, (4) 1,1,1 trichloroethane to ethane, and (5)
      phenylalanine to isoleucine. Two studies were performed to evaluate the
      dependence of the convergence of these calculations on MD simulation length and
      starting configuration. In the first study, each transformation started from the
      same well-equilibrated configuration and the simulation length was varied from
      230 to 2,540 ps. The results indicated that for transformations involving small
      structural changes, a simulation length of 860 ps is sufficient to obtain
      satisfactory convergence. In contrast, transformations involving relatively large
      structural changes, such as phenylalanine to isoleucine, require a significantly
      longer simulation length (>2,540 ps) to obtain satisfactory convergence. In the
      second study, the transformation was completed starting from three different
      configurations and using in each case 860 ps of MD simulation. The results from
      this study suggest that performing one long simulation may be better than
      averaging results from three different simulations using a shorter simulation
      length and three different starting configurations.

PMID- 19760107
TI  - Zinc transporter expression profiles in the rat prostate following alterations in
      dietary zinc.
AB  - Zinc plays important roles in numerous cellular activities and physiological
      functions. Intracellular zinc levels are strictly maintained by zinc homeostatic
      mechanisms. Zinc concentrations in the prostate are the highest of all soft
      tissues and could be important for prostate health. However, the mechanisms by
      which the prostate maintains high zinc levels are still unclear. In addition, the
      response of the prostate to alterations in dietary zinc is unknown. The current
      study explored cellular zinc levels and zinc transporter expression profiles in
      the lobes of the prostate during dietary marginal zinc depletion. Rats were given
      either zinc-adequate (ZA, 30 mg Zn/kg) or marginal zinc-deficient (MZD, 5 mg
      Zn/kg) diet for 9 weeks. In addition, a subgroup of the MZD rats was supplemented
      with phytase (1,500 unit/kg diet) to improve zinc bioavailability. We found that
      both zinc concentrations and ZnT2 expression in the prostate dorsolateral lobes
      were substantially higher than in the ventral lobes (P < 0.05). Marginal zinc
      depletion significantly decreased ZnT2 expression in the dorsolateral lobes (P <
      0.05), and phytase supplementation had a trend to increase ZnT2 expression. In
      addition, of all measured zinc transporters, only ZnT2 mRNA abundance was
      significantly correlated to the zinc concentrations in the dorsolateral lobe. No
      correlations were found between zinc transporter expression and zinc
      concentrations in the ventral lobes. These results indicate that ZnT2 may play a
      significant role in the maintenance of zinc homeostasis in the prostate.

PMID- 19760108
TI  - Zinc activates neutrophils' oxidative burst.
AB  - Zinc has been shown to disturb the innate host defense response by interfering in
      the activation of neutrophils and subsequent oxidative burst, although the exact
      role of this metal, either as an activator or inhibitor, remains a matter of
      controversy among research groups. These apparent discrepancies may be due to
      experimental settings, through modification of zinc availability to neutrophils,
      or to inaccurate detections of reactive species. Thus, the main objective of the
      present study was to provide clarification on the role of zinc on the activation
      of human neutrophils and the subsequent oxidative burst. For that purpose,
      different detection methods and incubation media were used. The obtained results
      showed that phosphate buffers (PBS and HBSS) complex with zinc and interfere with
      the results obtained with this metal. By using Tris-G, it was clearly
      demonstrated that zinc, at low concentrations (5-12.5 microM), activates NADPH
      oxidase, mainly via protein kinase C, leading to the formation of superoxide
      radical (O(2*-). Higher concentrations of zinc results on a rapid dismutation of
      O2*- to oxygen and hydrogen peroxide, which in turn is used by myeloperoxidase to
      generate hypochlorous acid (HOCl).

PMID- 19760109
TI  - Effects of tellurite on growth of Saccharomyces cerevisiae.
AB  - The effects of potassium tellurite on growth and survival of rho(+) and rho(0)
      Saccharomyces cerevisiae strains were investigated. Both rho(+) and rho(0)
      strains grew on a fermentable carbon source with up to 1.2 mM K(2)TeO(3), while
      rho(+) yeast cells grown on a non-fermentable carbon source were inhibited at
      tellurite levels as low as 50 muM suggesting that this metalloid specifically
      inhibited mitochondrial functions. Growth of rho(+) yeast cells in the presence
      of increasing amount of tellurite resulted in dose-dependent blackening of the
      culture, a phenomenon not observed with rho(0) cultures. Transmission electron
      microscopy of S. cerevisiae rho(+) cells grown in the presence of tellurite
      showed that blackening was likely due to elemental tellurium (Te(0)) that formed
      large deposits along the cell wall and small precipitates in both the cytoplasm
      and mitochondria.

PMID- 19760110
TI  - Kinetics of prolonged photoinhibition revisited: photoinhibited Photosystem II
      centres do not protect the active ones against loss of oxygen evolution.
AB  - Photoinhibition of Photosystem II (PSII) in lincomycin-treated leaves begins as a
      first-order reaction, but fluorescence measurements have suggested that after
      prolonged illumination, the number of active PSII centres stabilizes to 15-20% of
      control. The stabilization has been interpreted to indicate that photoinhibited
      PSII centres protect the remaining active centres against photoinhibition (Lee,
      Hong and Chow, Planta 212:332-342, 2001). In an attempt to study the mechanism of
      this protection, we measured the reaction kinetics of photoinhibition in
      lincomycin-treated pumpkin (Cucurbita pepo L.) and pepper (Capsicum annuum L.)
      leaves in vivo. The light-saturated rate of PSII oxygen evolution, assayed from
      thylakoids and isolated from the treated leaves, was used as a direct measure of
      the number of remaining active PSII centres, and the fluorescence parameters F
      (V)/F (M) and (F (V)/F (M))/F (0) (=1/F (0) - 1/F (M)) were measured for
      comparison. To our surprise, no stabilization of PSII activity was observed and
      photoinhibition followed first-order kinetics until PSII activity had virtually
      declined to zero. A series of in vitro experiments was carried out to see whether
      stabilization of PSII activity occurs if a particular combination of light
      intensity and wavelength range is applied, or if a specific PSII preparation is
      used as experimental material. The results of the in vitro experiments confirmed
      the in vivo result about persistent first-order kinetics. We conclude that
      photoinhibited PSII centres offer no measurable protection against
      photoinhibition.

PMID- 19760111
TI  - PAH mineralization and bacterial organotolerance in surface sediments of the
      Charleston Harbor estuary.
AB  - Semi-volatile organic compounds (SVOCs) in estuarine waters can adversely affect
      biota but watershed sources can be difficult to identify because these compounds
      are transient. Natural bacterial assemblages may respond to chronic, episodic
      exposure to SVOCs through selection of more organotolerant bacterial communities.
      We measured bacterial production, organotolerance and polycyclic aromatic
      hydrocarbon (PAH) mineralization in Charleston Harbor and compared surface
      sediment from stations near a known, permitted SVOC outfall (pulp mill effluent)
      to that from more pristine stations. Naphthalene additions inhibited an average
      of 77% of bacterial metabolism in sediments from the more pristine site (Wando
      River). Production in sediments nearest the outfall was only inhibited an average
      of 9% and in some cases, was actually stimulated. In general, the stations with
      the highest rates of bacterial production also were among those with the highest
      rates of PAH mineralization. This suggests that the capacity to mineralize PAH
      carbon is a common feature amongst the bacterial assemblage in these estuarine
      sediments and could account for an average of 5.6% of bacterial carbon demand (in
      terms of production) in the summer, 3.3% in the spring (April) and only 1.2% in
      winter (December).

PMID- 19760112
TI  - Biodegradation of N,N diethylaniline in a contaminated aquifer: Laboratory- and
      field-scale evidences.
AB  - The effectiveness of biosparging to mitigate N,N diethylaniline in aquifer was
      evaluated by measuring the time course of decrease in concentration of the
      aforementioned compound in aerobic microcosm experiments. The first-order kinetic
      constant for N,N diethylaniline aerobic biodegradation was estimated from
      microcosm data (0.037 +/- 0.004 d(-1)), and the value was consistent with the
      best-fitting value in the transport and reaction model of the aquifer (0.020 d(
      1)). Furthermore, the biodegradability of the compound was evaluated under
      anaerobic condition in microcosm experiments, which was supported by field
      modelling. There was no significant degradation in the anaerobic microcosm
      experiments, confirming the recalcitrance of N,N diethyl aniline under the
      aforementioned aquifer condition.

PMID- 19760113
TI  - Temperature response in electrosensors and thermal voltages in electrolytes.
AB  - Temperature sensation is increasingly well understood in several model organisms.
      One of the most sensitive organs to temperature changes is the functional
      electrosensor of sharks and their relatives; its extreme thermal responsiveness,
      in excised preparations, has not been mechanistically described. In recent years,
      conflicting reports have appeared concerning the properties of a hydrogel that
      fills the ampullae of Lorenzini. The appearance of a thermoelectric effect in the
      gel (or, using different methods, a reported lack thereof) suggested a link
      between the exquisite electrosense and the thermal response of the
      electroreceptors (or, alternately, denied that link). I review available
      electrophysiology evidence of the organ's temperature response, calculate a
      theoretical gel signal prediction using physical chemistry, analyze the strengths
      and weaknesses of the existing gel measurements, and discuss broader implications
      for the ampullae and temperature sensation.

PMID- 19760114
TI  - The challenge of developmentally appropriate care: predictive genetic testing in
      young people for familial adenomatous polyposis.
AB  - Predictive genetic tests for familial adenomatous polyposis (FAP) are routinely
      offered to young people during early adolescence. While this is not
      controversial, due to the medical benefit conferred by the test, it is
      nonetheless challenging as a consequence of the stage of life of the young
      people, and the simultaneous involvement of multiple family members. Despite
      these challenges, it is possible to ensure that the test is offered in such a way
      that it actively acknowledges and facilitates young people's developing autonomy
      and psychosocial well-being. In this paper we present findings from ten in-depth
      interviews with young people who have undergone predictive genetic testing for
      FAP (four male, six female; five gene-positive, five gene-negative; aged 10-17
      years at the time of their predictive test; aged 12-25 years at the time of their
      research interview). We present five themes that emerged from the interviews
      which highlight key ethical challenges associated with such testing. These are:
      (1) the significance of the test; (2) young people's lack of involvement in the
      decision to be tested; (3) young people's limited understanding; (4) provision of
      the blood test at the first visit; and (5) group testing of family members. We
      draw on these themes to make eight recommendations for future practice. Together,
      these recommendations highlight the importance of providing developmentally
      appropriate care to young people undergoing predictive genetic testing for FAP.

PMID- 19760115
TI  - Rolling circle amplification of genomic templates for inverse PCR (RCA-GIP): a
      method for 5'- and 3'-genome walking without anchoring.
AB  - We have devised an improved method of genome walking, named rolling circle
      amplification of genomic templates for Inverse PCR (RCA-GIP). The method is based
      on the generation of circular genomic DNA fragments, followed by rolling circle
      amplification of the circular genomic DNA using phi29 DNA polymerase without need
      for attachment of anchor sequences. In this way from the circular genomic DNA
      fragments, after RCA amplification, a large amount of linear concatemers is
      generated suitable for Inverse PCR template that can be amplified, sequenced or
      cloned allowing the isolation of the 3'- and 5'- of unknown ends of genomic
      sequences. To prove the concept of the proposed methodology, we used this
      procedure to isolate the promoter regions from different species. Herein as an
      example we present the isolation of four promoter regions from Crocus sativus, a
      crop cultivated for saffron production.

PMID- 19760116
TI  - Production of pure beta-glucan by Aureobasidium pullulans after pullulan
      synthetase gene disruption.
AB  - By disruption of the pullulan synthetase gene (pul) of Aureobasidium pullulans
      IMS822 KCTC11179BP, we constructed a mutant strain, A. pullulans NP1221, which
      produced a pure beta-glucan exopolysaccharide. The mutant NP1221 was white,
      whereas the wild-type strain produced a black dye. When we compared fermentation
      kinetics between wide-type and mutant strains, the mutant NP1221 did not produce
      pullulan. Substrate uptake rate and beta-glucan production were similar in both
      strains. However, the biomass yield of mutant NP1221 was 2.3-fold (9.2 g l(-1))
      greater than that of wild-type.

PMID- 19760117
TI  - Pr-1, a novel antifungal protein from pumpkin rinds.
AB  - A novel antifungal protein, M(r) = ca. 40 kDa, was isolated from pumpkin rind and
      designated Pr-1. When purified by anion exchange chromatography and HPLC, it
      inhibited growth of several fungi including Botrytis cinerea, Fusarium oxysporum,
      Fusarium solani and Rhizoctonia solani, as well as the yeast, Candida albicans,
      at 10-20 microM. It did not inhibit growth of Escherichia coli or Staphylococcus
      aureus even at 200 microM. Laser scanning microscopy of fungal cells exposed to
      rhodamine-labeled Pr-1 revealed that the protein accumulated and was localized on
      the cell surface. Uptake of the vital stain, SYTOX Green, was enhanced when
      fungal conidia were treated with Pr-1 suggesting that the protein has membrane
      permeabilization activity. Pr-1 was thermostable at 70 degrees C and did not lyse
      human red blood cells at 128 microM suggesting that the protein may be useful as
      an antifungal agent with little, if any human cytotoxicity.

PMID- 19760118
TI  - Diastereoselective synthesis of L: -threo-3,4-dihydroxyphenylserine by low
      specific L: -threonine aldolase mutants.
AB  - Diastereoselectivity-enhanced mutants of L: -threonine aldolase (L: -TA) for L: 
      threo-3,4-dihydroxyphenylserine (L: -threo-DOPS) synthesis were isolated by error
      prone PCR followed by a high-throughput screening. The most improved mutant was
      achieved from the mutant T3-3mm2, showing a 4-fold increase over the wild-type L:
      -TA. When aldol condensation activity was examined using whole cells of T3-3mm2,
      its de was constantly maintained at 55% during the batch reactions for 80 h,
      yielding 3.8 mg L: -threo-DOPS/ml.

PMID- 19760119
TI  - Fed-batch operation of an industrial cell culture process in shaken microwells.
AB  - Recently we have demonstrated batch suspension culture of mammalian cells in
      microwell plates. Here we describe a method for fed-batch culture of an
      industrially relevant GS-CHO (Glutamine Synthetase-Chinese Hamster Ovary) cell
      line in shaken 24-standard round well (24-SRW) plates. Use of a commercially
      available 'sandwich lid' and appropriate dilution of the bolus feeds counteracted
      liquid evaporation from the wells resulting in similar cell growth and antibody
      formation kinetics in both 24-SRW plates (800 mul) and shaken flasks (50 ml).
      Peak viable cell densities obtained were 8 +/- 0.5 x 10(6) and 9 +/- 1.3 x 10(6)
      ml(-1), respectively, while comparable final titres of a whole IgG of
      approximately 1.5 g l(-1) were recorded. Use of microwells provides at least a 50
      fold reduction in medium requirements compared to shake-flask and other culture
      devices currently used in early stage cell culture process development. The
      ability to run multiple wells in parallel and to automate culture operation also
      offers considerable enhancements in experimental throughput.

PMID- 19760120
TI  - Preparation of cross-linked carboxymethyl chitosan for repairing sciatic nerve
      injury in rats.
AB  - A successful nerve regeneration process was achieved with nerve repair tubes made
      up of 1-ethyl-3(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) cross
      linked carboxymethyl chitosan (CM-chitosan) with improved biodegradability.
      Chitosan has a very slow degradation rate, while the EDC cross-linked CM-chitosan
      tubes degraded to 30% of original weight during 8 weeks of incubation in lysozyme
      solution. In vitro cell culture indicated that the CM-chitosan films presented no
      cytotoxicity to Schwann cells. From in vivo studies using a 10 mm rat sciatic
      nerve defect model investigated by histomorphometry analysis, the average
      diameter of the fibers and the average thickness of myelin sheath in the CM
      chitosan tubes were 3.7 +/- 0.33 and 0.33 +/- 0.04 mum, respectively, which
      demonstrated equivalence to nerve autografts (the current "gold" standard);
      furthermore, the average fiber density in the CM-chitosan tubes was 20.5 x
      10(3)/mm(2), which was similar to that of autografts (21 x 10(3)/mm(2)) and
      significantly higher than that of common chitosan tubes (15.3 x 10(3)/mm(2)).

PMID- 19760121
TI  - Constitutive production of the receptor-binding domain of the F18 fimbriae on the
      surface of Lactococcus lactis using synthetic promoters.
AB  - Nine synthetic constitutive promoters with different activities were produced for
      the surface display of the receptor-binding domain of the F18 fimbrial adhesin
      FedF in Lactococcus lactis. The promoters were synthesized from an
      oligonucleotide, designed to allow for randomization of bases between defined
      lactococcal promoter consensus regions. However, promoters with spontaneous
      modifications were selected for fedF expression, indicating that the consensus
      promoter was too strong. The amount of FedF on the surface of the best performing
      promoter clone was comparable to the amount of FedF produced by a L. lactis
      strain with an optimized NICE expression system. Stability of FedF production
      further suggested that an optimal constitutive expression level was attained.

PMID- 19760122
TI  - Bioburden assessment of banked bone used for allografts.
AB  - Allograft bone is commonly used in reconstructive orthopaedic surgery and needs
      to be assessed for bioburden before transplant. The Microbiology Department of
      the South Eastern Area Laboratory Services (SEALS), located at the St. George
      Hospital, Sydney, has provided this service to the New South Wales (NSW) Bone
      Bank. This study reviewed the organisms isolated from femoral head allografts of
      living donors from the NSW Bone Bank over a 7-year period. It was found that
      growth was reported from 4.9% of samples with the predominant organism being
      coagulase-negative staphylococci. This review will focus on the micro-organisms
      isolated, the interaction of the laboratory with the bone bank, the relevance of
      the bioburden assessment in the overall quality process and patient safety.

PMID- 19760123
TI  - Chemo-radiotherapy in locally advanced squamous cell oesophageal cancer--are
      upper third tumours more responsive?
AB  - Before neoadjuvant therapy was widely applied, the prognosis of oesophageal
      cancer had been considered dependent on the location of the tumor, i.e. upper
      third cancers had had the worst prognosis. The aim of this retrolective study was
      to prove the efficiency of the neoadjuvant treatment, and to compare the response
      of esophageal cancer in different locations. Between January 1998 and September
      2005, 102 patients with locally advanced squamous cell oesophageal cancer
      received preoperative chemo-radiotherapy. In 40 cases the tumor was located in
      the upper third and in 62 cases in the middle third of the oesophagus. After a
      four-week-long treatment free period restaging was carried out and patients
      considered resectable were submitted to surgery. From 40 patients with upper
      third oesophageal cancer 28 underwent oesophageal resection or pharyngo
      laryngectomy. Thiry-five percent a complete histopathological remission was
      observed. From 62 patients with middle third oesophageal cancer 43 underwent
      oesophageal resection. Histological examination of the resected specimens
      documented complete response only in three patients. The median survival and the
      R0 resection rate were similar in the two groups. Although the resection rate,
      perioperative morbidity, mortality and the median survival were similar in the
      two groups, a significantly higher rate of complete response (p < 0,05) was
      observed in patients with upper third oesophageal cancer compared to patients
      with middle third oesophageal cancer. It seems that upper third oesophageal
      cancer has superior sensitivity to multimodal treatment therefore our results may
      support that upper third location is not an unfavorable prognostic factor any
      more.

PMID- 19760124
TI  - Phenotypic and molecular identification of Cellulosimicrobium cellulans isolated
      from Antarctic snow.
AB  - We report for the first time the isolation of Cellulosimicrobium cellulans from
      Antarctic snow. This strain demonstrated physiological traits that were markedly
      different from that of the mesophilic C. cellulans type strain DSM 43879(T). The
      dominant cell wall sugars in C. cellulans were glucose, galactose and mannitol
      whereas rhamnose was the only major sugar in the type strain. Cellular fatty acid
      patterns were dominated by 12-methyltetradecanoic acid (ai-C(15:0)), hexadecanoic
      acid (C(16:0)) and 14-methylhexadecanoic acid (ai-C(17:0)) but lacked iso fatty
      acids unlike the type strain. The ability of C. cellulans to survive in Antarctic
      snow could be due to these modified physiological properties that distinguish it
      from its mesophilic counterpart. Carbon utilization studies demonstrated that C.
      cellulans preferred complex carbon substrates over simple ones suggesting that it
      could play a potential role in carbon uptake in snow. Our study shows that this
      genus could be more cosmopolitan than hitherto thought of and is capable of
      living in extreme cold environments.

PMID- 19760125
TI  - Matrine suppresses breast cancer cell proliferation and invasion via VEGF-Akt-NF
      kappaB signaling.
AB  - Matrine has shown therapeutic and/or adjuvant therapeutic effects on the
      treatment of some patients with breast cancer. However, its mechanisms of action
      are largely unknown. To disclose the mechanisms, we investigated in vitro and ex
      vivo effects of matrine on the cancer cells. Our results confirmed that matrine
      significantly suppressed the proliferation of highly-metastatic human breast
      cancer MDA-MB-231 cell line. Matrine displayed synergistic effects with existing
      anticancer agents celecoxib (the inhibitor of cyclooxygenase-2), trichostatin A
      (the histone deacetylase inhibitor) and rosiglitazone against the proliferation
      and VEGF excretions in MDA-MB-231 cells. Matrine induced the apoptosis and cell
      cycle arrest by reducing the ratios of Bcl-2/Bax protein and mRNA levels in the
      cancer cells. Matrine significantly reduced the invasion, MMP-9/MMP-2 activation,
      Akt phosphorylation, nuclear factor kappaB p-65 expression and DNA binding
      activity, and mRNA levels of MMP-9, MMP-2, EGF and VEGFR1 in MDA-MB-231 cells.
      Collectively, our results suggest that matrine inhibits the cancer cell
      proliferation and invasion via EGF/VEGF-VEGFR1-Akt-NF-kappaB signaling pathway.

PMID- 19760126
TI  - Serum-free transfection of CHO cells with chemically defined transfection systems
      and investigation of their potential for transient and stable transfection.
AB  - The generation of transgenic cell lines is acquired by facilitating the uptake
      and integration of DNA. Unfortunately, most of the systems generating stable
      expression systems are cost and time-consuming and transient expression is
      optimized to generate milligram amounts of the recombinant protein. Therefore we
      improved and compared two transfection systems, one based on cationic liposomes
      consisting of DOTAP/DOPE and the second one on polyethylenimine (PEI). Both
      systems have been used as chemically defined transfection systems in combination
      with serum-free cultivated host cell line. At first we had determined the
      toxicity and ideal ratio of DNA to PEI followed by determination of the optimal
      transfection conditions in order to achieve maximum transfection efficiency. We
      then directly compared DOTAP/DOPE and PEI in transient transfection experiments
      using enhanced green fluorescence protein (EGFP) and a human monoclonal antibody,
      mAb 2F5, as a model protein. The results which were achieved in case of EGFP were
      more than 15% transfectants at a viability of 85%. Despite the fact that
      expression of the mAb was found negligible we used both techniques to generate
      stable mAb 2F5 expressing cell lines that underwent several cycles of screening
      and amplification with methotrexate, and resulted in cell lines with similar
      volumetric production titers. These experiments serve to demonstrate the
      potential of stable cell lines even in case where the transient systems did not
      show satisfying results.

PMID- 19760127
TI  - Effects of theanine on growth of human lung cancer and leukemia cells as well as
      migration and invasion of human lung cancer cells.
AB  - The aim of this study is to investigate the effects of theanine, a tea
      characteristic amino acid, on human lung cancer and leukemia cells. In the
      present study, we have demonstrated that theanine suppressed the in vitro and ex
      vivo growth of human non-small cell lung cancer A549 and leukemia K562 cell lines
      in dose- and time-dependant manners. In addition, theanine displayed the
      inhibitory effect on the migration of A549 cells. More importantly, theanine
      enhanced the anticancer activity of anticancer agents such as trichostatin A (the
      histone deacetylase inhibitor), berbamine and norcantharidin (the anticancer
      drugs in China) by strongly reducing the viability and/or migration rate in A549
      cells. In addition, theanine significantly suppressed A549 cell invasion.
      Suppression of A549 cell migration may be one of the important mechanisms of
      action of theanine against the A549 cell invasion. Our present results suggest
      that theanine may have the wide therapeutic and/or adjuvant therapeutic
      application in the treatment of human lung cancer and leukemia.

PMID- 19760128
TI  - Canine amniotic membrane transplantation for corneal reconstruction after the
      excision of dermoids in dogs.
AB  - Transplantation of canine amniotic membrane (AM) in conjunction with a third
      eyelid flap was performed after the removal of large dermoids by keratectomy and
      conjunctivectomy on 7 eyes of 7 dogs. Corneal epithelialization was completed
      within 2 weeks after the transplantation. Five eyes attained normal transparency
      of the cornea within 5 weeks. Slight pigmentation of the bulbar conjunctiva at
      the limbus was observed in 1 dog that had pre-existing pigmentary keratitis.
      Neovascularization and scarring of the cornea and impaired vision were not found
      in any dogs at 8 weeks after the transplantation. In conclusion, transplantation
      of canine AM can promote corneal healing after the excision of large dermoids in
      dogs.

PMID- 19760129
TI  - A survey of integral alpha-helical membrane proteins.
AB  - Membrane proteins serve as cellular gatekeepers, regulators, and sensors. Prior
      studies have explored the functional breadth and evolution of proteins and
      families of particular interest, such as the diversity of transport-associated
      membrane protein families in prokaryotes and eukaryotes, the composition of
      integral membrane proteins, and family classification of all human G-protein
      coupled receptors. However, a comprehensive analysis of the content and
      evolutionary associations between membrane proteins and families in a diverse set
      of genomes is lacking. Here, a membrane protein annotation pipeline was developed
      to define the integral membrane genome and associations between 21,379 proteins
      from 34 genomes; most, but not all of these proteins belong to 598 defined
      families. The pipeline was used to provide target input for a structural genomics
      project that successfully cloned, expressed, and purified 61 of our first 96
      selected targets in yeast. Furthermore, the methodology was applied (1) to
      explore the evolutionary history of the substrate-binding transmembrane domains
      of the human ABC transporter superfamily, (2) to identify the multidrug
      resistance-associated membrane proteins in whole genomes, and (3) to identify
      putative new membrane protein families.

PMID- 19760130
TI  - Syntactic sequencing in Hebbian cell assemblies.
AB  - Hebbian cell assemblies provide a theoretical framework for the modeling of
      cognitive processes that grounds them in the underlying physiological neural
      circuits. Recently we have presented an extension of cell assemblies by
      operational components which allows to model aspects of language, rules, and
      complex behaviour. In the present work we study the generation of syntactic
      sequences using operational cell assemblies timed by unspecific trigger signals.
      Syntactic patterns are implemented in terms of hetero-associative transition
      graphs in attractor networks which cause a directed flow of activity through the
      neural state space. We provide regimes for parameters that enable an unspecific
      excitatory control signal to switch reliably between attractors in accordance
      with the implemented syntactic rules. If several target attractors are possible
      in a given state, noise in the system in conjunction with a winner-takes-all
      mechanism can randomly choose a target. Disambiguation can also be guided by
      context signals or specific additional external signals. Given a permanently
      elevated level of external excitation the model can enter an autonomous mode,
      where it generates temporal grammatical patterns continuously.

PMID- 19760131
TI  - Both dorsal and ventral flaps can be used in previously circumcised hypospadic
      adults with comparable success rates.
AB  - OBJECTIVE: To compare dorsal and ventral dartos flap outcomes for tubularized
      incised-plate urethroplasty (TIPU) in terms of success, complication rates and
      cosmetic appearance in adult circumcised hypospadic men. METHODS: Forty-two
      circumcised adult men underwent primary distal or midpenile hypospadias repair
      for cosmetic reasons by a single surgeon in a prospective randomized trial.
      Twenty-two patients were randomly selected for TIPU repair with dorsal (Group1,
      mean age 22.3 years) dartos flap as second layer. Twenty patients were randomly
      selected for TIPU repair with ventral dartos flap (Group2, mean age 21.1 years).
      Satisfaction questionnaires were answered by patients before surgery and at
      postoperative 6 weeks. The operating surgeon also filled in the form blindly at
      the same postoperative period. The differences between pre and postoperative
      satisfaction scores for each group were also evaluated. Preoperatively, all cases
      were evaluated with uroflowmetry and compared with postoperative results measured
      at 6th week of surgery. P < 0.05 was considered as significant. RESULTS: Mean
      follow-up was 24 months (4-28). Complications were encountered in 18 and 20% of
      the patients in groups 1 and 2, respectively. Complications were urethrocutaneous
      fistula, meatal stenosis, retrusive/proximal meatus and residual curvature.
      Success rates were 82 and 80%, respectively. No differences were seen in overall
      satisfaction between the two groups (P = 0.07). CONCLUSION: Outcome of
      hypospadias repair in circumcised adults for cosmetic reasons is similar to
      uncircumcised hypospadics previously mentioned in the literature. Both dorsal and
      ventral flaps can be used in previously circumcised hypospadic adults with
      comparable satisfaction and complication rates and uroflow findings.

PMID- 19760132
TI  - Peritoneal dialysis glossary 2009.
AB  - A number of attempts to create a commonly accepted terminology regarding
      definitions and terms used for clinical entities, methods, problems, and
      materials encountered by health professionals involved in peritoneal dialysis
      (PD) were undertaken in the past, the last one in 1990. Later on, some relevant
      sporadic attempts in a number of textbooks have been made, but they did not
      include the whole spectrum of PD. This glossary is an attempt to address the need
      for a universally accepted PD terminology including the latest advances in PD
      connection systems and fluids.

PMID- 19760133
TI  - Risk factors for complications of endoscopic submucosal dissection in gastric
      tumors: analysis of 478 lesions.
AB  - PURPOSE: Endoscopic submucosal dissection (ESD) technique has facilitated en bloc
      removal of widely spread lesions from the stomach. This retrospective study aimed
      to determine factors associated with serious complications of ESD. METHODS:
      Between December 2001 and March 2007, we have performed ESD for 478 lesions in
      436 patients. We experienced 39 patients with post-operative bleeding and 17
      patients with perforation. Risk factors of patients who received ESD in gastric
      mucosal tumors for complications were evaluated, focusing on resected size,
      location, scar lesions, operation time, and experience of endoscopists. We
      evaluated the patients' background characteristics including sex, age, body mass
      index (kg/m(2)), drug history of anticoagulant, and underlying diseases including
      cerebrovascular disorder, ischemic heart disease, liver dysfunction, renal
      dysfunction, hyperuricemia, hypertension and diabetes mellitus. RESULTS:
      Multivariate analysis indicated a risk factor for perforation was long operation
      time. Multivariate analysis indicated a significant risk factor for post
      operative bleeding was size of the resected tumor. CONCLUSIONS: This study
      indicated risk factors for serious complications of ESD. Large resected tumor
      size was a risk factor for post-operative bleeding, while long operation time was
      a risk factor for perforation. Information regarding operation risk factors
      should be useful for planning strategies for ESD.

PMID- 19760134
TI  - Inhibition of hepatitis C virus replication by chloroquine targeting virus
      associated autophagy.
AB  - BACKGROUND: Autophagy has been reported to play a pivotal role on the replication
      of various RNA viruses. In this study, we investigated the role of autophagy on
      hepatitis C virus (HCV) RNA replication and demonstrated anti-HCV effects of an
      autophagic proteolysis inhibitor, chloroquine. METHODS: Induction of autophagy
      was evaluated following the transfection of HCV replicon to Huh-7 cells. Next, we
      investigated the replication of HCV subgenomic replicon in response to treatment
      with lysosomal protease inhibitors or pharmacological autophagy inhibitor. The
      effect on HCV replication was analyzed after transfection with siRNA of ATG5,
      ATG7 and light-chain (LC)-3 to replicon cells. The antiviral effect of
      chloroquine and/or interferon-alpha (IFNalpha) was evaluated. RESULTS: The
      transfection of HCV replicon increased the number of autophagosomes to about
      twofold over untransfected cells. Pharmacological inhibition of autophagic
      proteolysis significantly suppressed expression level of HCV replicon. Silencing
      of autophagy-related genes by siRNA transfection significantly blunted the
      replication of HCV replicon. Treatment of replicon cells with chloroquine
      suppressed the replication of the HCV replicon in a dose-dependent manner.
      Furthermore, combination treatment of chloroquine to IFNalpha enhanced the
      antiviral effect of IFNalpha and prevented re-propagation of HCV replicon.
      Protein kinase R was activated in cells treated with IFNalpha but not with
      chloroquine. Incubation with chloroquine decreased degradation of long-lived
      protein leucine. CONCLUSION: The results of this study suggest that the
      replication of HCV replicon utilizes machinery involving cellular autophagic
      proteolysis. The therapy targeted to autophagic proteolysis by using chloroquine
      may provide a new therapeutic option against chronic hepatitis C.

PMID- 19760135
TI  - Femoral bone mineral density and bone mineral content in bromocriptine-treated
      pregnant and lactating rats.
AB  - Since hyperprolactinemia was found to induce osteopenia in the metaphysis of long
      bone in non-mated female rats, pregnant and lactating rats with sustainedly high
      plasma prolactin (PRL) levels might also exhibit some changes in their long
      bones. We performed a longitudinal study in pregnant, lactating and post-weaning
      rats, using dual-energy X-ray absorptiometry to demonstrate site-specific changes
      (i.e., metaphysis vs. diaphysis) in femoral bone mineral density (BMD) and
      content (BMC). The results showed that femoral metaphyseal BMD and BMC were
      higher when compared to their age-matched controls during pregnancy, before
      decreasing in late lactation and post-weaning. On the other hand, femoral
      diaphyseal BMC increased during pregnancy, early lactating and mid-lactating
      periods without change during late lactation and post-weaning. After 7 days of
      bromocriptine administration which inhibited endogenous PRL secretion, the
      lactation-induced increases in BMC during early and mid-lactating periods were
      abolished. Moreover, a decrease in metaphyseal BMD during late lactation was
      restored to the control levels by bromocriptine. However, bromocriptine did not
      antagonize the pregnancy-induced increases in BMD and BMC. It could be concluded
      that the effect of PRL on bone was variable during the reproductive periods.
      While having no effect on femoral BMD and BMC during pregnancy, PRL was
      responsible for bone gain in early and mid-lactating periods, but induced bone
      loss during late lactating period.

PMID- 19760136
TI  - Seasonal shift in factors controlling net ecosystem production in a high Arctic
      terrestrial ecosystem.
AB  - We examined factors controlling temporal changes in net ecosystem production
      (NEP) in a high Arctic polar semi-desert ecosystem in the snow-free season. We
      examined the relationships between NEP and biotic and abiotic factors in a
      dominant plant community (Salix polaris-moss) in the Norwegian high Arctic. Just
      after snowmelt in early July, the ecosystem released CO(2) into the atmosphere. A
      few days after snowmelt, however, the ecosystem became a CO(2) sink as the leaves
      of S. polaris developed. Diurnal changes in NEP mirrored changes in light
      incidence (photosynthetic photon flux density, PPFD) in summer. NEP was
      significantly correlated with PPFD when S. polaris had fully developed leaves,
      i.e., high photosynthetic activity. In autumn, NEP values decreased as S. polaris
      underwent senescence. During this time, CO(2) was sometimes released into the
      atmosphere. In wet conditions, moss made a larger contribution to NEP. In fact,
      the water content of the moss regulated NEP during autumn. Our results indicate
      that the main factors controlling NEP in summer are coverage and growth of S.
      polaris, PPFD, and precipitation. In autumn, the main factor controlling NEP is
      moss water content.

PMID- 19760137
TI  - Embryology of Petrosavia (Petrosaviaceae, Petrosaviales): evidence for the
      distinctness of the family from other monocots.
AB  - The affinities of Petrosavia, a rare, leafless, mycoheterotrophic genus composed
      of two species indigenous to East to Southeast Asia, have long been uncertain.
      However, recent molecular analyses show that the genus is sister to Japonolirion
      osense. Japonolirion and Petrosavia comprise the Petrosaviaceae, which are now
      placed in its own order, Petrosaviales, distinct from other monocots based on
      molecular analyses. We conducted an embryological study of Petrosavia, comparing
      it to Japonolirion, as well as to basal monocots (Acorus and Araceae) and more
      derived monocots (Nartheciaceae, Velloziaceae, and Triuridaceae). Our results
      showed that Petrosavia is very similar in embryology to Japonolirion, with both
      genera sharing a glandular anther tapetum, simultaneous cytokinesis in microspore
      mother cells, anatropous and crassinucellate ovules, T-shaped tetrads of
      megaspores, ab initio Cellular-type endosperm, and a mature seed coat composed of
      the exotesta, endotesta, and endotegmen. The two genera of Petrosaviaceae are
      clearly distinct from Acorus, and all Araceae, Nartheciaceae, Velloziaceae, and
      Triuridaceae genera in various combinations of characters. Thus, both molecular
      and embryological evidence support the distinctness of the Petrosaviaceae from
      other monocots and its placement in its own order, Petrosaviales.

PMID- 19760138
TI  - Phylogenetic analyses of nucleotide sequences confirm a unique plant
      intercontinental disjunction between tropical Africa, the Caribbean, and the
      Hawaiian Islands.
AB  - Phylogenetic analyses of nucleotide sequences of the internal transcribed spacers
      and 5.8 regions of the nuclear ribosomal DNA and of the trnH-psbA spacer of the
      chloroplast genome confirm that the three taxa of the Jacquemontia ovalifolia
      (Choicy) Hallier f. complex (Convolvulaceae) form a monophyletic group. Levels of
      nucleotide divergence and morphological differentiation among these taxa support
      the view that each should be recognized as distinct species. These three species
      display unique intercontinental disjunction, with one species endemic to Hawaii
      (Jacquemontia sandwicensis A. Gray.), another restricted to eastern Mexico and
      the Antilles [Jacquemontia obcordata (Millspaugh) House], and the third confined
      to East and West Africa (J. ovalifolia). The Caribbean and Hawaiian species are
      sister taxa and are another example of a biogeographical link between the
      Caribbean Basin and Polynesia. We provide a brief conservation review of the
      three taxa based on our collective field work and investigations; it is apparent
      that J. obcordata is highly threatened and declining in the Caribbean.

PMID- 19760139
TI  - Liver transplantation for hepatocellular carcinoma: the Hong Kong experience.
AB  - Orthotopic liver transplantation (OLT) is the best treatment option for selected
      patients with hepatocellular carcinoma (HCC) with the background of cirrhosis
      since this treatment modality can cure both diseases at once. Over the years, the
      applicability of OLT for HCC has evolved. In Asia, including Hong Kong, a
      shortage of deceased donor liver grafts is a universal problem having to be faced
      in all transplant centers. Living-donor liver transplant (LDLT) has therefore
      been developed to counteract organ shortage and the high prevalence of HCC. The
      application of LDLT for HCC is a complex process involving donor voluntarism,
      selection criteria for the recipient and justification with respect to long-term
      survival in comparison to the result of deceased donor liver transplant. This
      article reviews the authors' experience with OLT for HCC patients in Hong Kong,
      with emphasis on the applicability and outcome of LDLT for HCC. Donor voluntarism
      has a significant impact on the application of LDLT. "Fast-track" LDLT in the
      setting of recurrence following curative treatment carries a high risk of
      recurrence even though the tumor stage fulfills the standard criteria. Although
      the survival outcome may be worse following LDLT than DDLT for HCC, LDLT is still
      the main treatment option for patients with transplantable HCC in Hong Kong, and
      a reasonable survival outcome can be achieved in selected patients with extended
      indications. It is particularly true that LDLT provides the only hope for
      patients with advanced HCC under the constricting problem of organ shortage.

PMID- 19760140
TI  - Indocyanine green R15 ratio depends directly on liver perfusion flow rate.
AB  - BACKGROUND: Indocyanine green (ICG) is a synthetic dye that is widely used to
      evaluate liver function in critically ill patients, before liver resection or
      after liver transplantation. Controversy still exists about the impact exerted on
      the ICG ratio after 15 min (ICG R15) by differences in liver perfusion rates,
      hyperdynamic states, or patient cardiac output. We studied the role of different
      liver perfusion rates on the ICG R15 ratio in a normothermic extracorporeal liver
      perfusion system under standardized conditions. METHODS: Livers from landrace
      pigs (40-50 kg) were perfused with fresh porcine blood. Normal and high perfusion
      rates were defined as 1 ml and 2 ml/g liver/min, respectively. Perfusate pressure
      of the hepatic artery and portal vein were within the physiological range in both
      groups. According to manufacturer's instructions, 0.5 mg of ICG per kg was
      applied and the ICG R15 was calculated. Calculations were based on fifteen
      experiments in five liver perfusions. Bile production, liver function and
      histology were analyzed. RESULTS: All perfusions were characterized by
      physiological bile production, lack of hepatocellular damage and normal
      histology. ICG R15 ratio in group I, perfused with 1 ml/g liver, was 18.9 +/- 6%.
      In group II, perfused with 2 ml/g liver, the ICG R15 ratio was 7.2 +/- 3%. The
      difference between groups 1 and 2 was statistically significant (p < 0.05).
      CONCLUSION: ICG R15 is reliable within one group at defined perfusion rates.
      Doubled perfusion rates contribute to higher ICG clearance. For clinical
      application we would like to suggest considering cardiac output of the patient
      for interpretation of ICG ratios.

PMID- 19760142
TI  - Identifying indices of learning for alpha neurofeedback training.
AB  - Neurofeedback has been around for decades and has applications for both clinical
      and healthy populations yet there is no standard method for measuring learning or
      a way of defining successful learning. Thus the aim of this study was to focus on
      alpha neurofeedback and examine changes in three different measures: amplitude,
      percent time, and integrated alpha, across four methods: within sessions, across
      sessions, within sessions compared to baseline, and across sessions compared to
      baseline. Participants completed 10 weekly sessions of eyes open alpha (8-12 Hz)
      neurofeedback training (NFT) at Pz. Whilst all three measures showed changes
      within sessions, the inclusion of baselines revealed that such changes
      represented a return to baseline levels rather than an increase in alpha. Changes
      across sessions were only evident in amplitude and inclusion of baseline showed
      that NFT did not elicit any changes beyond baseline levels. Given this a case is
      made for incorporating baseline measures when attempting to identify evidence of
      learning. It is also suggested that both amplitude and percent time measures are
      used independently rather than incorporate them into a more conservative and less
      sensitive integrated measure. Finally, focusing on within sessions changes may be
      a more useful approach in identifying changes resulting from NFT.

PMID- 19760141
TI  - Regulation of ER molecular chaperone prevents bone loss in a murine model for
      osteoporosis.
AB  - Endoplasmic reticulum (ER) stress response is important for protein maturation in
      the ER. Some murine models for bone diseases have provided significant insight
      into the possibility that pathogenesis of osteoporosis is related to ER stress
      response of osteoblasts. We examined a possible correlation between osteoporosis
      and ER stress response. Bone specimens from 8 osteoporosis patients and 8 disease
      controls were used for immunohistochemical analysis. We found that ER molecular
      chaperones, such as BiP (immunoglobulin heavy-chain binding protein) and PDI
      (protein-disulfide isomerase) are down-regulated in osteoblasts from osteoporosis
      patients. Based on this result, we hypothesized that up-regulation of ER
      molecular chaperones in osteoblasts could restore decreased bone formation in
      osteoporosis. Therefore, we investigated whether treatment of murine model for
      osteoporosis with BIX (BiP inducer X), selective inducer BiP, could prevent bone
      loss. We found that oral administration of BIX effectively improves decline in
      bone formation through the activation of folding and secretion of bone matrix
      proteins. Considering these results together, BIX may be a potential therapeutic
      agent for the prevention of bone loss in osteoporosis patients.

PMID- 19760143
TI  - The need for individualization in neurofeedback: heterogeneity in QEEG patterns
      associated with diagnoses and symptoms.
AB  - Very diverse assessment procedures are utilized by neurofeedback practitioners,
      many of which are not based on careful examination of raw EEG data followed by
      scientifically objective quantitative EEG (QEEG) database comparisons. Research
      is reviewed demonstrating the great heterogeneity in the EEG patterns associated
      with various diagnoses and symptoms. The fact that most patients qualify for dual
      diagnoses, with co-morbid psychiatric and medical conditions present, complicates
      the ability of clinicians to estimate what electrophysiological patterns may be
      associated with symptoms. In such cases treatment planning is characterized by a
      great deal of guesswork and experimentation. Peer reviewed publications have
      documented that neurofeedback treatment can sometimes be associated with both
      transient side effects as well as more serious negative effects. It is believed
      that the lack of comprehensive and objective assessment of brain functioning may
      increase the risk of neurofeedback either being ineffective or causing iatrogenic
      harm. QEEG provides reliable, non-invasive, objective, culture-free and
      relatively low cost evaluation of brain functioning, permitting individualization
      of treatment and added liability protection.

PMID- 19760144
TI  - Reports from the DSM-V Work Group on sexual and gender identity disorders.

PMID- 19760145
TI  - The relationship between rejection sensitivity and compliant condom use.
AB  - Those who are rejection sensitive anxiously expect and readily perceive
      rejection. Rejection sensitivity is hypothesized to predict behavior; however,
      this link may be more evident in some contexts than others. The current study
      examined the link between rejection sensitivity and condom use. Australian young
      adults in romantic (n = 649, 70% female) and casual (n = 144, 76.2% female)
      relationship contexts completed measures on rejection sensitivity, condom use
      preferences, and condom use. Regression analysis showed that rejection
      sensitivity predicted condom use when participants' condom use preferences were
      at odds with those they thought their partner held. Specifically, highly
      rejection-sensitive individuals who preferred more frequent condom use reported
      using condoms less often, if that was what they thought their partners wanted.
      The results lend support to the model of rejection sensitivity in that
      individuals comply more with their perceived partner's preferences if they are
      more rejection-sensitive. The results also highlight the need to take the
      situational context into consideration when examining links between personality
      dispositions and behavior.

PMID- 19760146
TI  - A controllably anisotropic conductivity or diffusion phantom constructed from
      isotropic layers.
AB  - Phantoms with controllable and well-defined anisotropy are needed to test methods
      for imaging electrical anisotropy. We developed and tested a phantom that had
      properties similar to a homogeneous anisotropic conductive medium. The phantom
      was constructed with alternate slices of isotropic gel having different
      conductivities. The degree of anisotropy in the phantom could be varied easily by
      changing the relative conductivity of the two gels. We tested the stability of
      several phantoms and found their properties were maintained for approximately 8 h
      following construction. The phantom has application to electrical impedance
      tomography, magnetic resonance electrical impedance tomography, EEG and ECG
      source imaging and diffusion tensor imaging.

PMID- 19760147
TI  - Finger thermoregulatory model assessing functional impairment in Raynaud's
      phenomenon.
AB  - Raynaud's Phenomenon (RP) is a paroxysmal vasospastic disorder of small arteries,
      pre-capillary arteries, and cutaneous arteriovenous shunts of the extremities,
      typically induced by cold exposure and emotional stress. RP is either primary
      (PRP) or secondary to systemic sclerosis. In this study we use Control System
      Theory to model finger thermoregulatory processes in response to a standardized
      cold challenge (a diagnostic test routinely performed for differential diagnosis
      of RP). The proposed model is based on a homeostatic negative feedback loop,
      characterized by five distinct parameters which describe how the control
      mechanisms are activated and maintained. Thermal infrared imaging data from 14
      systemic sclerosis subjects (SSc), 14 PRP, and 16 healthy control subjects (HCS)
      were processed. HCS presented the fastest active recovery, with the highest gain.
      PRP presented the slowest and weakest recovery, mostly due to passive heat
      exchange with the environment. SSc presented an intermediate behavior, with the
      longest delay of response onset. The estimated model parameters elucidated the
      level of functional impairment expressed in the various forms of this disease.

PMID- 19760148
TI  - Computational simulations of magnetic particle capture in arterial flows.
AB  - The aim of Magnetic Drug Targeting (MDT) is to concentrate drugs, attached to
      magnetic particles, in a specific part of the human body by applying a magnetic
      field. Computational simulations are performed of blood flow and magnetic
      particle motion in a left coronary artery and a carotid artery, using the
      properties of presently available magnetic carriers and strong superconducting
      magnets (up to B approximately 2 T). For simple tube geometries it is deduced
      theoretically that the particle capture efficiency scales as [see text], with Mn
      (p) the characteristic ratio of the particle magnetization force and the drag
      force. This relation is found to hold quite well for the carotid artery. For the
      coronary artery, the presence of side branches and domain curvature causes
      deviations from this scaling rule, viz. eta approximately Mn (p) (beta) , with
      beta > 1/2. The simulations demonstrate that approximately a quarter of the
      inserted 4 microm particles can be captured from the bloodstream of the left
      coronary artery, when the magnet is placed at a distance of 4.25 cm. When the
      same magnet is placed at a distance of 1 cm from a carotid artery, almost all of
      the inserted 4 microm particles are captured. The performed simulations,
      therefore, reveal significant potential for the application of MDT to the
      treatment of atherosclerosis.

PMID- 19760149
TI  - Longitudinal assessment of BMI in relation to ADT use among early stage prostate
      cancer survivors.
AB  - INTRODUCTION: The use of androgen deprivation therapy (ADT) for prostate cancer
      is on the rise, but its adverse side effects may include increased fat mass and
      decreased lean muscle mass. The net effect of ADT on BMI is unknown. METHODS:
      Primary, incident cases of early stage prostate cancer (n = 473) were identified
      from the Buffalo VA Medical Center tumor registry and matched to body size,
      demographic, comorbidity, and treatment exposure data from veteran medical
      records. Multilevel modeling was used to assess the association between ADT and
      changes in BMI. RESULTS: On average, survivors were overweight at diagnosis and
      showed small, non-significant changes in BMI over time. However, among those
      survivors with a history of ADT, a significant decrease of 0.05 BMI units per
      year was associated with each additional dose of ADT (p < 0.001). When the
      association between BMI rate of change and ADT was allowed to vary with respect
      to age, additional doses of ADT predicted stronger decreases in BMI for younger
      survivors as compared to older survivors (p < 0.05). Neither a history of surgery
      nor radiation influenced the association between ADT use and BMI. CONCLUSIONS:
      Declines in BMI in relation to ADT exposure may be reflective of unfavorable
      changes in body composition, especially decreased muscle mass, that is most
      pronounced in younger survivors. IMPLICATIONS FOR CANCER SURVIVORS: Survivors on
      ADT may benefit from close monitoring of physical functioning and referral for
      exercise interventions to preserve muscle mass and improve health related quality
      of life.

PMID- 19760150
TI  - Confronting chemobrain: an in-depth look at survivors' reports of impact on work,
      social networks, and health care response.
AB  - INTRODUCTION: Mild cognitive impairment following chemotherapy is one of the most
      commonly reported post treatment symptoms by breast cancer survivors. This
      deterioration in cognitive function, commonly referred to as "chemobrain" or
      "chemofog," was largely unacknowledged by the medical community until recent
      years. Although chemobrain has now become the subject of more vigorous
      exploration, little is known about this specific phenomenon's psychosocial impact
      on breast cancer survivors. This research documents in-depth the effects that
      cognitive impairment has on women's personal and professional lives, and our data
      suggest that greater attention needs to be focused on this arena of survivorship.
      METHODS: The results are based on an in-depth qualitative study of 74 white and
      African American breast cancer survivors in California who experience post
      treatment side effects. The data reported herein were obtained through the use of
      focus groups and in-depth interviews. RESULTS: Our data indicate that cognitive
      impairment can be problematic for survivors, with many asserting that it is their
      most troublesome post treatment symptom. Survivors report diminished quality of
      life and daily functioning as a result of chemobrain. Respondents detail a range
      of coping strategies that they are forced to employ in order to manage their
      social and professional lives. DISCUSSIONS/CONCLUSIONS: Chemobrain significantly
      impairs a proportion of cancer survivors, at great cost to them economically,
      emotionally, and interpersonally. This suggests that more research needs to be
      conducted on the psychosocial ramifications of post treatment symptoms in order
      to inform the efforts of the medical and mental health communities as well as the
      support networks of survivors. IMPLICATIONS FOR CANCER SURVIVORS: A better and
      broader understanding of the effects of cognitive impairment both in the medical
      community and among lay people could pave the way for improved social and
      psychological services for this population.

PMID- 19760151
TI  - Racial/ethnic differences in quality of life after diagnosis of breast cancer.
AB  - INTRODUCTION: Most studies on quality of life of breast cancer survivors have not
      had adequate representation of ethnic minorities. The purpose of this study was
      to determine whether racial/ethnic differences in quality of life exist between
      white, African American, and Latina women in the early stages of survivorship.
      METHODS: 2268 women were identified by two Surveillance, Epidemiology and End
      Results (SEER) registries (6/05-2/07) and asked to complete a survey (mean 9
      months post-diagnosis, 72.1% response rate). Latina and African American women
      were over-sampled. Regression models compared quality of life across
      race/ethnicity (white, African American, Latina [low vs. high acculturation]),
      sequentially controlling for sociodemographics, clinical, and treatment factors.
      RESULTS: There were significant racial/ethnic differences in quality of life
      controlling for sociodemographics, clinical factors and treatment factors. Lower
      acculturated Latinas compared to whites had significantly lower functional well
      being, emotional well-being, and breast cancer concerns (p values < 0.05).
      African Americans had significantly higher emotional well-being than whites. Age,
      co-morbidities, cancer stage, and chemotherapy also influenced quality of life. A
      significant interaction was found between race/ethnicity and age for physical
      well-being (p = 0.041) and for emotional well-being (p = 0.042). Specifically,
      racial/ethnic differences were only observed among older women (>or=50 years),
      with less acculturated Latinas reporting the lowest quality of life. CONCLUSIONS:
      Racial/ethnic differences in quality of life exist during the cancer survivorship
      period. Latinas with low acculturation are a particularly vulnerable subgroup.
      IMPLICATIONS: Greater attention should be devoted to identifying women
      disproportionately affected by breast cancer and developing interventions
      targeting their unique survivorship concerns.

PMID- 19760152
TI  - Association of health beliefs and colonoscopy use among survivors of colorectal
      cancer.
AB  - OBJECTIVES: Clinical practice guidelines recommend ongoing testing (surveillance)
      for colorectal cancer survivors because they remain at risk for both local
      recurrences and second primary tumors. However, survivors often do not receive
      colorectal cancer surveillance. We used the Health Belief Model (HBM) to identify
      health beliefs that predict intentions to obtain routine colonoscopies among
      colorectal cancer survivors. METHODS: We completed telephone interviews with 277
      colorectal cancer survivors who were diagnosed 4 years earlier, between 2003 and
      2005, in North Carolina. The interview measured health beliefs, past preventive
      behaviors, and intentions to have a routine colonoscopy in the next 5 years.
      RESULTS: In bivariate analyses, most HBM constructs were associated with
      intentions. In multivariable analyses, greater perceived likelihood of colorectal
      cancer (OR = 2.00, 95% CI = 1.16-3.44) was associated with greater intention to
      have a colonoscopy. Survivors who already had a colonoscopy since diagnosis also
      had greater intentions of having a colonoscopy in the future (OR = 9.47, 95% CI =
      2.08-43.16). CONCLUSIONS: Perceived likelihood of colorectal cancer is an
      important target for further study and intervention to increase colorectal cancer
      surveillance among survivors. Other health beliefs were unrelated to intentions,
      suggesting that the health beliefs of colorectal cancer survivors and
      asymptomatic adults may differ due to the experience of cancer.

PMID- 19760154
TI  - Keep talking about it: HIV/AIDS-related communication and prior HIV testing in
      Tanzania, Zimbabwe, South Africa, and Thailand.
AB  - Informal, interpersonal communication within a community about HIV and AIDS, or
      lack of such communication, may influence community members' uptake of voluntary
      counseling and testing. Drawing from Noelle-Neumann's spiral of silence theory,
      this study examined the association between communication about HIV/AIDS and
      prior HIV testing in communities in Tanzania, Zimbabwe, South Africa, and
      Thailand. Participants (N = 14,818) in 48 communities across five sites
      throughout the four countries completed a behavioral survey assessing
      communication, prior voluntary counseling and testing (VCT) uptake, social norms,
      stigma, and sexual risk. Site-specific logistic regression models demonstrated
      that frequent conversations about HIV were significantly associated with prior
      HIV testing at every site. Odds ratios for each site ranged from 1.885 to 3.085,
      indicating a roughly doubled or tripled chance of past VCT uptake. Results
      indicate that verbal communication may be an important mechanism for increasing
      health behaviors and inclusion in future interventions should be considered.

PMID- 19760155
TI  - Community-based services for homeless adults experiencing concurrent mental
      health and substance use disorders: a realist approach to synthesizing evidence.
AB  - Consultations with community-based service providers in Toronto identified a lack
      of strong research evidence about successful community-based interventions that
      address the needs of homeless clients experiencing concurrent mental health and
      substance use disorders. We undertook a collaborative research effort between
      academic-based and community-based partners to conduct a systematic evidence
      synthesis drawing heavily from Pawson's realist review methodology to focus on
      both whether programs are successful and why and how they lead to improved
      outcomes. We examined scholarly and nonscholarly literature to explore program
      approaches and program elements that lead to improvements in mental health and
      substance use disorders among homeless individuals with concurrent disorders
      (CD). Information related to program contexts, elements, and successes and
      failures were extracted and further supplemented by key informant interviews and
      author communication regarding reviewed published studies. From the ten programs
      that we reviewed, we identified six important and promising program strategies
      that reduce mental health and, to a far lesser degree, substance use problems:
      client choice in treatment decision-making, positive interpersonal relationships
      between client and provider, assertive community treatment approaches, providing
      supportive housing, providing supports for instrumental needs, and nonrestrictive
      program approaches. These promising program strategies function, in part, by
      promoting and supporting autonomy among homeless adults experiencing CD. Our
      realist informed review is a useful methodology for synthesizing complex
      programming information on community-based interventions.

PMID- 19760156
TI  - Ketamine and the myenteric plexus in intestinal ischemia/reperfusion injury.
AB  - BACKGROUND AND AIMS: Intestinal ischemia/reperfusion (I/R) is a common clinical
      entity with severe consequences. We studied the effects of ketamine and the
      participation of the myenteric plexus in I/R injury. METHODS: Rats were divided
      into six groups: sham, IR (30 min ischemia/60 min reperfusion), KET+IR (50 mg/kg
      i.p. ketamine injection before I/R), DEN (myenteric plexus ablated with
      benzalkonium chloride (BAC) and sham operation performed), DEN+IR (BAC treated
      and I/R induced), and DEN+KET+IR (BAC treated, ketamine administered, and I/R
      induced). Serum concentrations of p-selectin, intracellular adhesion molecule-1
      (ICAM-1), and antithrombin III (ATIII) were measured, and tissue samples were
      obtained for histological analysis. RESULTS: IR group had higher intestinal
      mucosa injury and elevated serum concentrations of ICAM-1 and p-selectin, as well
      as ATIII depletion, compared with sham group (P < 0.05). In KET+IR group these
      alterations were significantly reduced (P < 0.05). DEN group showed ICAM-1
      elevations when compared with sham group (P < 0.05), and DEN+IR group showed no
      difference in any parameter compared with IR group. However, ketamine
      administration in group DEN+KET+IR had no effect on any parameter when compared
      with DEN+IR group. CONCLUSIONS: Ketamine was able to diminish alterations induced
      by I/R. Myenteric plexus ablation with BAC treatment alone had no effects on
      intestinal I/R injury. However, this procedure abolished ketamine's protective
      effects. Ketamine seems to require an intact enteric nervous system to exert its
      protective action.

PMID- 19760157
TI  - Factors contributing to hospitalization for gastroparesis exacerbations.
AB  - BACKGROUND: The clinical course of patients with gastroparesis is characterized
      by symptomatic exacerbations often necessitating hospitalization. AIMS: To
      investigate precipitating factors leading to hospitalization for exacerbation of
      symptoms in patients with gastroparesis. METHODS: This was a retrospective review
      of 103 admissions (63 patients) for gastroparesis exacerbation. RESULTS:
      Etiologic categories for gastroparetic patients were diabetic (43%), idiopathic
      (39%), and post surgical (8%). Poor glycemic control was present in 36%,
      infection in 19% (12 urinary tract infections and two bacteremia), and
      noncompliance with or intolerance of, medications in six and 5% of patients,
      respectively. Fasting morning cortisol concentrations were ?3 mcg/dl in 9%.
      Elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were
      seen in 34 of 65 (52%) and 11 of 50 patients (22%), respectively. No identifiable
      infection was found in 74 and 45% of patients with elevated ESR and elevated CRP,
      respectively. ESR and CRP were higher when patients were symptomatic
      necessitating hospitalization (26.2 +/- 6.6 mm/h and 1.6 +/- 1.0 mg/l) compared
      with when they were seen in outpatient follow-up and less symptomatic (10.3 +/-
      2.9 mm/h and 0.3 +/- 0.1 mg/l; P = 0.0001 and P = 0.211, respectively).
      CONCLUSIONS: Poor glycemic control, infection, noncompliance with/intolerance of
      medications, and, perhaps, adrenal insufficiency were contributory factors
      leading to hospitalizations of gastroparetic patients. Hospitalized patients with
      gastroparesis exacerbations had elevated ESR and CRP levels. Although many
      patients with elevated inflammatory markers had evidence of infection, some did
      not. Assessment of inflammatory markers may help indicate those gastroparetic
      patients in whom a search for infection should be undertaken.

PMID- 19760158
TI  - Demographic characteristics of hospitalized IBD patients.
AB  - BACKGROUND AND AIMS: The Nationwide Inpatient Sample of the Healthcare Cost and
      Utilization Project (HCUP) was used to study the recent demographic
      characteristics of patients with Crohn's disease (CD) or ulcerative colitis (UC).
      METHODS: HCUP data of the period 1997-2006 were extracted. The data were
      stratified by the categories pertaining to patient demographics, such as age
      group, sex, race, insurance type, income group, residence in metropolitan area
      and region of the United States, as well as categories pertaining to hospital
      characteristics, such as type of ownership, teaching status, location, and bed
      size. The distributions of inpatients among different categories were compared
      between CD or UC and all other diagnoses, using odds ratios and their 95%
      confidence intervals for comparison. RESULTS: The data revealed a slight female
      predominance in CD (1.08, 1.09-1.09) and a slight male predominance in UC (1.15,
      1.14-1.15). Compared to patients with other diagnoses, patients with inflammatory
      bowel disease tended to be white (CD: 2.47, 2.45-2.50; UC: 2.13, 2.10-2.15), more
      affluent (CD: 1.44, 1.43-1.45; UC: 1.59, 1.58-1.61), live in metropolitan areas
      (CD: 1.09, 1.08-1.10; UC: 1.26, 1.25-1.27) and in the Northeast of the United
      States (CD: 1.27, 1.27-1.28; UC: 1.44, 1.43-1.45). CONCLUSIONS: These patterns
      confirm previously described characteristics of patients with inflammatory bowel
      disease and show that such characteristics still apply to present patient
      populations.

PMID- 19760159
TI  - Lovastatin overcomes gefitinib resistance in human non-small cell lung cancer
      cells with K-Ras mutations.
AB  - Lovastatin is a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase
      inhibitor. Its inhibitory action on HMG-CoA reductase leads to depletion of
      isoprenoids, which inhibits post-translational modification of RAS. In this
      study, we investigated the effect of combining lovastatin with gefitinib on
      gefitinib-resistant human non-small cell lung cancer (NSCLC) cell lines with K
      Ras mutations. Antitumor effects were measured by growth inhibition and 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Effects on apoptosis
      were determined by flow cytometry, DNA fragmentation, and immunoblots. Protein
      levels of RAS, AKT/pAKT, and RAF/ERK1/2 in cancer cells were analyzed by
      immunoblot. Compared with gefitinib alone, a combination of gefitinib with
      lovastatin showed significantly enhanced cell growth inhibition and cytotoxicity
      in gefitinib-resistant A549 and NCI-H460 human NSCLC cells. In addition,
      lovastatin combination treatment significantly increased gefitinib-related
      apoptosis, as determined by fluorescence microscopy and flow cytometric analysis.
      These effects correlated with up-regulation of cleaved caspase-3, poly (ADP
      ribose) polymerase (PARP), and Bax and down-regulation of Bcl-2. The combination
      of lovastatin and gefitinib effectively down-regulated RAS protein and suppressed
      the phosphorylation of RAF, ERK1/2, AKT, and EGFR in both cell lines. Taken
      together, these results suggest lovastatin can overcome gefitinib resistance, in
      NSCLC cells with K-Ras mutations, by down regulation of RAS protein, which leads
      to inhibition of both RAF/ERK and AKT pathways.

PMID- 19760160
TI  - Knowledge, attitudes, and beliefs regarding weight gain during pregnancy among
      Hispanic women.
AB  - Pregnancy weight gain may be a risk factor for the development of obesity
      highlighting the importance of identifying psychosocial risk factors for
      pregnancy weight gain. The goal of this qualitative pilot study was to evaluate
      knowledge, attitudes and beliefs regarding weight gain during pregnancy among
      predominantly Puerto Rican women, a group with higher rates of obesity as
      compared to non-Hispanic white women. We conducted four focus groups stratified
      by level of acculturation and BMI. Women reported receiving advice about
      pregnancy weight gain predominantly from nutritionists and family members rather
      than from their physicians. The majority of overweight/obese women reported that
      they had not received any recommendations for weight gain during pregnancy from
      physicians. Pregnancy weight gain advice was not consistent with the 1990
      Institute of Medicine Guidelines. Overall, attitudes towards weight gain
      recommendations differed by weight status, whereas feelings and dietary beliefs
      about weight gain differed according to level of acculturation. Our findings
      inform behavior change strategies for meeting pregnancy weight gain
      recommendations.

PMID- 19760162
TI  - Intimate partner violence and health care-seeking patterns among female users of
      urban adolescent clinics.
AB  - To assess the prevalence of intimate partner violence (IPV) and associations with
      health care-seeking patterns among female patients of adolescent clinics, and to
      examine screening for IPV and IPV disclosure patterns within these clinics. A
      self-administered, anonymous, computerized survey was administered to female
      clients ages 14-20 years (N = 448) seeking care in five urban adolescent clinics,
      inquiring about IPV history, reasons for seeking care, and IPV screening by and
      IPV disclosure to providers. Two in five (40%) female urban adolescent clinic
      patients had experienced IPV, with 32% reporting physical and 21% reporting
      sexual victimization. Among IPV survivors, 45% reported abuse in their current or
      most recent relationship. IPV prevalence was equally high among those visiting
      clinics for reproductive health concerns as among those seeking care for other
      reasons. IPV victimization was associated with both poor current health status
      (AOR 1.57, 95% CI 1.03-2.40) and having foregone care in the past year (AOR 2.59,
      95% CI 1.20-5.58). Recent IPV victimization was associated only with past 12
      month foregone care (AOR 2.02, 95% CI 1.18-3.46). A minority (30%) reported ever
      being screened for IPV in a clinical setting. IPV victimization is pervasive
      among female adolescent clinic attendees regardless of visit type, yet IPV
      screening by providers appears low. Patients reporting poor health status and
      foregone care are more likely to have experienced IPV. IPV screening and
      interventions tailored for female patients of adolescent clinics are needed.

PMID- 19760163
TI  - Pediatric vaccination and vaccine-preventable disease acquisition: associations
      with care by complementary and alternative medicine providers.
AB  - This study investigated provider-based complementary/alternative medicine use and
      its association with receipt of recommended vaccinations by children aged 1-2
      years and with acquisition of vaccine-preventable disease by children aged 1-17
      years. Results were based on logistic regression analysis of insurance claims for
      pediatric enrollees covered by two insurance companies in Washington State during
      2000-2003. Primary exposures were use of chiropractic, naturopathy, acupuncture,
      or massage practitioner services by pediatric enrollees or members of their
      immediate families. Outcomes included receipt by children aged 1-2 years of four
      vaccine combinations (or their component vaccines) covering seven diseases, and
      acquisition of vaccine-preventable diseases by enrollees aged 1-17 years.
      Children were significantly less likely to receive each of the four recommended
      vaccinations if they saw a naturopathic physician. Children who saw chiropractors
      were significantly less likely to receive each of three of the recommended
      vaccinations. Children aged 1-17 years were significantly more likely to be
      diagnosed with a vaccine-preventable disease if they received naturopathic care.
      Use of provider-based complementary/alternative medicine by other family members
      was not independently associated with early childhood vaccination status or
      disease acquisition. Pediatric use of complementary/alternative medicine in
      Washington State was significantly associated with reduced adherence to
      recommended pediatric vaccination schedules and with acquisition of vaccine
      preventable disease. Interventions enlisting the participation of
      complementary/alternative medicine providers in immunization awareness and
      promotional activities could improve adherence rates and assist in efforts to
      improve public health.

PMID- 19760164
TI  - Exploring knowledge and attitudes related to pregnancy and preconception health
      in women with chronic medical conditions.
AB  - Women with chronic medical conditions are at increased risk for pregnancy-related
      complications, yet little research has addressed how women with diabetes,
      hypertension, and obesity perceive their pregnancy-associated risks or make
      reproductive health decisions. Focus groups were conducted with 72 non-pregnant
      women stratified by chronic condition (diabetes, hypertension, obesity) and by
      previous live birth. Participants discussed their intention for future pregnancy,
      preconception health optimization, perceived risk of adverse pregnancy outcomes,
      and contraceptive beliefs. Four major themes were identified, with some variation
      across medical conditions and parity: (1) Knowledge about pregnancy risks related
      to chronic medical conditions was limited; (2) Pregnancy intentions were affected
      by diabetes and hypertension, (3) Knowledge about optimizing preconception health
      was limited; and (4) Lack of control over ability to avoid unintended pregnancy,
      including limited knowledge about how medical conditions might affect
      contraceptive choices. Women with diabetes and hypertension, but not obesity,
      were generally aware of increased risk for pregnancy complications, and often
      expressed less intention for future pregnancy as a result. However, diabetic and
      hypertensive women had little knowledge about the specific complications they
      were at risk for, even among those who had previously experienced pregnancy
      complications. Neither chronic condition nor perceived risk ensured intent to
      engage in preconception health promotion. We observed knowledge deficits about
      pregnancy-related risks in women with diabetes, hypertension, and obesity, as
      well as lack of intent to engage in preconception health promotion and pregnancy
      planning. These findings have important implications for the development of
      preconception care for women with chronic medical conditions.

PMID- 19760165
TI  - Early Childhood Longitudinal Study-Birth Cohort: a welcome addition to the
      maternal and child health field and its data bases.

PMID- 19760166
TI  - Association of maternal medical conditions and unfavorable birth outcomes:
      findings from the 1996-2003 Mississippi linked birth and death data.
AB  - This study aimed to identify factors contributing to high rates of preterm birth
      (PTB), low birth weight (LBW) and infant mortality in Mississippi while
      considering both traditional risk factors and maternal medical conditions. The
      retrospective cohort study used 1996-2003 Mississippi linked birth and infant
      death files. Multiple logistic regression was used to investigate association
      between maternal medical conditions and unfavorable birth outcomes. Along with
      traditional risk factors, hypertension was significantly associated with PTB and
      LBW. Women with hypertension were about 2.2 and 3.2 times as likely to have PTB
      and LBW, respectively. Hydramnios/oligohydramnios increased 1.8-4.4 folds of risk
      for PTB, LBW and infant death and was significantly associated with the
      unfavorable birth outcomes. Non-Hispanic black women were about 1.5-2.0 times as
      likely to have an unfavorable birth outcome compared to non-Hispanic white women.
      Maternal education and prenatal care effect appeared to be modified by maternal
      race. Certain maternal medical conditions may be contributing to PTB, LBW and
      infant mortality rates identifying preconception and prenatal healthcare as
      possible strategies for reducing unfavorable outcomes. Results suggest that
      different risk profiles for unfavorable outcomes may exist according to maternal
      race highlighting the need to consider racial groups separately when further
      exploring the sociodemographic and/or health-related factors that contribute to
      unfavorable birth outcomes.

PMID- 19760167
TI  - Development of a new method to preserve caprine cauda epididymal spermatozoa in
      situ at -10 degrees C with electrolyte free medium.
AB  - PURPOSE: In-situ preservation of cauda epididymal spermatozoa at -10 degrees C
      with electrolyte free media for obtaining maximum functional gametes than
      preservation at 5 degrees C. METHODS: Electrolyte free media prepared with
      soybean lecithin-glycerol, Coenzyme Q10 - glycerol and soybean lecithin -
      Coenzyme Q10- glycerol were inoculated separately into ligated cauda
      epididymides, equilibrated 2 h at 5 degrees C, wrapped with aluminium foil and
      freezed at - 10 degrees C. Spermatozoan characters were evaluated 7 and 21 days
      after thawing at 38.5 degrees C in a water bath for 5 min. RESULTS: Spermatozoan
      characteristics were diminished gradually and significantly (p < 0.001, p < 0.05)
      between the media and observation days. Soybean lecithin-CoenzymeQ10-glycerol
      effectively protected spermatozoa against cold shock where spermatozoan
      progressive motility, viability, hypo-osmotic swelling positivity were 30.2 +/-
      0.62; 45.2 +/- 0.82 and 41.6 +/- 0.79 percent respectively on day 21. CONCLUSION:
      This method can be adopted in field conditions for transportation of frozen
      epididymides and re-utilization of maximum functional gametes to conserve
      valuable animals after postmortem / slaughter.

PMID- 19760168
TI  - Is gestation in Prader-Willi syndrome affected by the genetic subtype?
AB  - BACKGROUND: Prader-Willi syndrome (PWS) is a complex genetic disorder with errors
      in genomic imprinting, generally due to a paternal deletion of chromosome 15q11
      q13 region. Maternal disomy 15 (both 15s from the mother) is the second most
      common form of PWS resulting from a trisomic zygote followed by trisomy rescue in
      early pregnancy and loss of the paternal chromosome 15. However, trisomy 15 or
      mosaicism for trisomy 15 may be present in the placenta possibly leading to
      placental abnormalities affecting gestational age and delivery. METHODS AND
      SUBJECTS: We examined growth and gestational data from 167 PWS infants (93 males
      and 74 females; 105 infants with 15q11-q13 deletion and 62 infants with maternal
      disomy 15) to determine if there are differences in gestation between the two
      genetic subtypes. RESULTS: No significant differences in growth data (birth
      weight, length, head circumference) or average gestational ages were found
      between the two genetic subgroups. However, post-term deliveries (> 42 weeks
      gestation) were more common in the maternal disomy group (i.e., 12 of 62 infants)
      compared with the deletion group (i.e., 7 of 105 infants) (chi-square test =
      6.22; p < 0.02). The distribution of gestational ages in the 15q11-q13 deletion
      group was more bell-shaped or normal while the distribution in the maternal
      disomy group suggested a bimodal pattern. CONCLUSIONS: Maternal disomy 15 in PWS
      may contribute to disturbances in gestational age and delivery by impacting on
      placental structure or function secondary to the abnormal chromosomal number in
      the placental cells or in mechanisms leading to the maternal disomy status in PWS
      infants.

PMID- 19760169
TI  - Birth of a healthy male infant after transfer of vitrified-warmed blastocysts
      derived from intracytoplasmic sperm injection with vitrified-warmed oocytes and
      frozen-thawed spermatozoa.
AB  - PURPOSE: To report a successful delivery of a healthy baby after transfer of
      vitrified-warmed blastocysts derived from introcytoplasmic sperm injection (ICSI)
      with vitrified-warmed oocytes and frozen-thawed sperm. METHODS: A female patient
      and her husband with non-obstructive azoospermia received a transfer of vitrified
      warmed blastocysts from vitrified-warmed oocytes and frozen-thawed sperm. The
      main outcome measures were fertilization, pregnancy and birth. RESULTS: Nine
      oocytes were matured and vitrified. When the vitrified oocytes were warmed, six
      survived with good quality morphology. Using ICSI, frozen-thawed sperm was
      injected into the six warmed oocytes that survived, and the fertilization rate
      was 100%. The zygotes were cultured, and five of six early embryos became
      blastocysts. One of them was transferred, but pregnancy was not achieved. The
      second time around, two vitrified-warmed blastocysts were transferred resulting
      in pregnancy, and a healthy boy was delivered. CONCLUSIONS: This is a rare case
      of a successful birth using a vitrified-warmed blastocyst grown after ICSI with a
      vitrified-warmed oocyte and frozen-thawed sperm.

PMID- 19760170
TI  - Sellar collision tumor involving pituitary gonadotroph adenoma and chondroma: a
      potential clinical diagnosis.
AB  - We report on a 74-year-old male patient who presented with progressive
      neuroophthalmologic symptoms soon after the administration of a long-acting
      gonadotropin-releasing hormone agonist for treatment of a prostate cancer.
      Imaging revealed a destructively growing and extensively calcified sellar mass
      inconsistent with a pituitary adenoma. A transseptal transsphenoidal tumor mass
      reduction yielded a histological diagnosis of a collision tumor comprised of a
      gonadotroph adenoma intermingled with osteochondroma. We discuss a potential
      causal relationship between the administration of the long-acting gonadotropin
      releasing hormone agonist and the sudden appearance of the previously unsuspected
      sellar lesion. Although the association of these two tumors is very likely
      coincidental, the possibility of causal relationship is addressed.

PMID- 19760171
TI  - Platelet hyperactivity during exercise leading to iterative coronary stent
      thrombosis: clinical implications.
AB  - Exercise may induce platelet activation in spite of using antiplatelet treatment.
      We present a case where the initial acute coronary syndrome and the iterative
      stent thrombosis always occurred after intense and prolonged physical effort. For
      this patient the at rest response to platelet inhibition with antiplatelet
      treatments was assessed as adequate, but after exercise the patient developed
      platelet activation which could be the trigger of his stent thrombosis.

PMID- 19760172
TI  - NMR solution structure of the N-terminal domain of subunit E (E1-52) of A1AO ATP
      synthase from Methanocaldococcus jannaschii.
AB  - The N-termini of E and H of A1AO ATP synthase have been shown to interact and an
      NMR structure of N-terminal H1-47 has been solved recently. In order to
      understand the E-H assembly and the N-terminal structure of E, the truncated
      construct E1-52 of Methanocaldococcus jannaschii A1AO ATP synthase was produced,
      purified and the solution structure of E1-52 was determined by NMR spectroscopy.
      The protein is 60.5 A in length and forms an alpha helix between the residues 8
      48. The molecule is amphipathic with a strip of hydrophobic residues, discussed
      as a possible helix-helix interaction with neighboring subunit H.

PMID- 19760174
TI  - Neuroprotective and neurological properties of Melissa officinalis.
AB  - Melissa officinalis has traditionally been used due to its effects on nervous
      system. Both methanolic and aqueous extracts were tested for protective effects
      on the PC12 cell line, free radical scavenging properties and neurological
      activities (inhibition of MAO-A and acetylcholinesterase enzymes and affinity to
      the GABA(A)-benzodiazepine receptor). The results suggest that the plant has a
      significant (P < 0.05) protective effect on hydrogen peroxide induced toxicity in
      PC12 cells. The radical scavenging properties were also investigated in cells and
      in cell free systems, where this plant was shown to be a good free radical
      scavenger. The MAO-A bioassay was also performed to detect possible
      antidepressant activities demonstrating that both extracts inhibited this enzyme,
      which has a key role in neurotransmitters metabolism. However, no activity was
      detected in the acetylcholinesterase and GABA assays. In general, the methanolic
      extract was more effective than the aqueous.

PMID- 19760175
TI  - Regulation of [3H] D-aspartate release from mammalian isolated retinae by
      hydrogen sulfide.
AB  - Hydrogen sulfide (H(2)S), can produce pharmacological effects on neural and non
      neural tissues from several mammalian species. The present study investigates the
      pharmacological action of H(2)S, (using sodium hydrosulfide, NaHS, and/or sodium
      sulfide, Na(2)S as donors) on amino acid neurotransmission (using [(3)H] D: 
      aspartate as a marker for glutamate) from isolated, superfused bovine and porcine
      retinae. Isolated neural retinae were incubated in Krebs solution containing
      [(3)H] D: -aspartate at 37 degrees C. Release of [(3)H] D: -aspartate was
      elicited by high potassium (K(+) 50 mM) pulse. Both NaHS and Na(2)S donors caused
      an inhibition of K(+)-evoked [(3)H] D: -aspartate release from isolated bovine
      retinae without affecting basal [(3)H] D: -aspartate efflux yielding IC(50)
      values of 0.006 and 6 microm, respectively. Furthermore, NaHS inhibited
      depolarization-evoked release of [(3)H] D: -aspartate from isolated porcine
      retinae with an IC(50) value of 8 microM. The inhibitory action of NaHS on [(3)H]
      D: -aspartate release from porcine retinae was blocked by propargyglycine, a
      selective inhibitor of cystathionine gamma-lyase (CSE). Our results indicate that
      H(2)S donors can inhibit amino acid neurotransmission from both isolated bovine
      and porcine retinae, an effect that is dependent, at least in part, on intramural
      biosynthesis of H(2)S.

PMID- 19760176
TI  - Tensaw virus genome sequence and its relation to other Bunyaviridae.
AB  - Tensaw virus (TSV) belongs to the genus Orthobunyavirus within the Bunyaviridae
      family. Although TSV does not cause hemorrhagic fever as some other members of
      its family, serological studies have shown that serum from Florida residents
      react against TSV indicating viral infection in humans. In this study, the three
      RNA genome segments of a TSV isolated from Anopheles crucians mosquitoes
      collected in North Central Florida in 2006 and a TSV isolate obtained from the
      CDC, Fort Collins, were sequenced and compared to other Bunyaviridae. The
      placement of the TSVs within the Bunyamwera serogroup was confirmed by
      phylogenetic analysis of the inferred amino acid (aa) sequence of proteins coded
      by each of the RNA segments separately as well as by the combined tree of the
      same three inferred proteins. The N terminal glycoprotein (Gn) encoded by the M
      segment contained the 18 conserved Cysteines present in Bunyamwera and California
      serogroups, the two glycosylation sites, and residues considered potential
      proteolytic cleavage sites conserved in other Bunyaviridae. The TSV L protein
      displayed all the strictly conserved amino acids in the four conserved regions
      known to be catalytically active for the RNA dependent RNA polymerase
      transcriptase and replicase activities. The amino acid conservation between the
      two TSV viral isolates was 100, 99.4, and 99.6% for the S, M, and L segments,
      respectively.

PMID- 19760173
TI  - BACE and gamma-secretase characterization and their sorting as therapeutic
      targets to reduce amyloidogenesis.
AB  - Secretases are named for enzymes processing amyloid precursor protein (APP), a
      prototypic type-1 membrane protein. This led directly to discovery of novel
      Aspartyl proteases (beta-secretases or BACE), a tetramer complex gamma-secretase
      (gamma-SC) containing presenilins, nicastrin, aph-1 and pen-2, and a new role for
      metalloprotease(s) of the ADAM family as a alpha-secretases. Recent advances in
      defining pathways that mediate endosomal-lysosomal-autophagic-exosomal
      trafficking now provide targets for new drugs to attenuate abnormal production of
      fibril forming products characteristic of AD. A key to success includes not only
      characterization of relevant secretases but mechanisms for sorting and transport
      of key metabolites to abnormal vesicles or sites for assembly of fibrils. New
      developments we highlight include an important role for an 'early recycling
      endosome' coated in retromer complex containing lipoprotein receptor LRP-II
      (SorLA) for switching APP to a non-amyloidogenic pathway for alpha-secretases
      processing, or to shuttle APP to a 'late endosome compartment' to form Abeta or
      AICD. LRP11 (SorLA) is of particular importance since it decreases in sporadic AD
      whose etiology otherwise is unknown.

PMID- 19760177
TI  - FHIT gene sequence variants and reduced Fhit protein expression in glioblastoma
      multiforme.
AB  - Molecular studies have an important role in the elucidation of the mechanisms
      involved in Glioblastoma multiforme (GBM) development. The occurrence of FHIT
      gene alterations, which has an important role in different cancers, has not yet
      been studied well in GBM. We aimed to investigate the occurrence of alterations
      of FHIT gene sequence and protein expression in the GBMs. Sequence alterations in
      exons 5-9 of the FHIT gene were screened in 63 GBMs using the single-strand
      conformational polymorphism method, followed by DNA sequencing. Additionally, the
      level of Fhit protein expression in tissues of 48 tumors was assessed by
      immunohistochemistry (IHC). In our investigation, FHIT gene alterations in the
      coding region were detected in 11 of the 63 GBM cases (17.5%). Two different
      sequence variants were determined: one novel missense variant (G-->C transition
      at codon 49) and one previously described silent alteration (C-->T transition at
      codon 88). Using web-based programs, such as SIFT and ESEfinder, it was
      determined that both alterations might have caused significant modification on
      protein function. In addition, we identified a previously reported an intronic
      polymorphism (T-->A transition at IVS8-17) in 47.5% of cases as a similar rate
      (45%) in the control group. Moreover, it was observed that Fhit protein
      expression was reduced in 87.5% of tumors. In conclusion, the reduction or loss
      of Fhit protein expression by genetic alterations or epigenetic mechanisms in GBM
      might be associated with brain tumorigenesis.

PMID- 19760179
TI  - Incomplete formation of intramolecular disulfide bond triggers degradation and
      aggregation of human consensus interferon-alpha mutant by Pichia pastoris.
AB  - Previous study has shown that the degradation and aggregation of recombinant
      human consensus interferon-alpha mutant (cIFN) were serious when cIFN was
      secreted to bioreactor by Pichia pastoris. In this study, we showed that this
      phenomenon was concomitant well with the formation of the doublets of cIFN
      monomers that could be seen clearly on sodium dodecyl sulfate polyacrylamide gel
      electrophoresis (SDS-PAGE). The doublets were a mixture of two isomers formed by
      cIFN with different disulfide bonds and identified that the upper cIFN in
      doublets contains only one disulfide bond while the lower cIFN contains intact
      disulfide bonds by a novel method termed protein laddering map on SDS-PAGE. In
      addition, the instability of cIFN with different disulfide bond forms is also
      analyzed through a novel in vitro conversion assay based on incubation with
      different concentrations of beta-mercaptoethanol. The results showed that only a
      wound such as cleavage of only one disulfide bond could be fatal to cIFN
      stability. If the disulfide bonds in cIFN monomers were broken, three kinds of
      aggregates would be formed easily: covalent aggregates, non-covalent aggregates,
      and unknown dimers. Likewise, the unfolded species also displayed reduced
      stability to proteolysis. These results indicate that the incomplete formation of
      disulfide bond in cIFN secreted to fermentation broth triggers severe degradation
      and aggregation of cIFN, which result in sharp decrease of bioactivity of cIFN in
      bioreactor.

PMID- 19760178
TI  - Achievements and new knowledge unraveled by metagenomic approaches.
AB  - Metagenomics has paved the way for cultivation-independent assessment and
      exploitation of microbial communities present in complex ecosystems. In recent
      years, significant progress has been made in this research area. A major
      breakthrough was the improvement and development of high-throughput next
      generation sequencing technologies. The application of these technologies
      resulted in the generation of large datasets derived from various environments
      such as soil and ocean water. The analyses of these datasets opened a window into
      the enormous phylogenetic and metabolic diversity of microbial communities living
      in a variety of ecosystems. In this way, structure, functions, and interactions
      of microbial communities were elucidated. Metagenomics has proven to be a
      powerful tool for the recovery of novel biomolecules. In most cases, functional
      metagenomics comprising construction and screening of complex metagenomic DNA
      libraries has been applied to isolate new enzymes and drugs of industrial
      importance. For this purpose, several novel and improved screening strategies
      that allow efficient screening of large collections of clones harboring
      metagenomes have been introduced.

PMID- 19760181
TI  - Insertional mutagenesis screening identifies the zinc finger homeodomain 2 (zfh2)
      gene as a novel factor required for embryonic leg development in Tribolium
      castaneum.
AB  - The genetic control of leg development is well characterized in the fly
      Drosophila melanogaster. These control mechanisms, however, must differ to some
      degree between different insect species to account for the morphological
      diversity of thoracic legs in the insects. The legs of the flour beetle Tribolium
      castaneum differ from the Drosophila legs in their developmental mode as well as
      in their specific morphology especially at the larval stage. In order to identify
      genes involved in the morphogenesis of the Tribolium larval legs, we have
      analyzed EGFP enhancer trap lines of Tribolium. We have identified the zfh2 gene
      as a novel factor required for normal leg development in Tribolium. RNA
      interference with zfh2 function leads to two alternative classes of leg
      phenotype. The loss of a leg segment boundary and the generation of ectopic
      outgrowths in one class of phenotype suggest a role in leg segmentation and
      segment growth. The malformation of the pretarsal claw in the second class of
      phenotype suggests a role in distal development and the morphogenesis of the claw
      shaped morphology of the pretarsus. This suggests that zfh2 is involved in the
      regulation of an unidentified target gene in a concentration-dependent manner.
      Our results demonstrate that enhancer trap screens in T. castaneum have the
      potential to identify novel gene functions regulating specific developmental
      processes.

PMID- 19760182
TI  - Induction of otic structures by canonical Wnt signalling in medaka.
AB  - The Wnt family of signalling proteins is known to participate in multiple
      developmental decisions during embryogenesis. We misexpressed Wnt1 in medaka
      embryos and observed anterior truncations, similar to those described for ectopic
      activation of canonical Wnt signalling in other species. Interestingly, when we
      induced a heat-shock Wnt1 transgenic line exactly at 30% epiboly, we observed
      multiple ectopic otic vesicles in the truncated embryos. The vesicles then fused,
      forming a single large ear structure. These "cyclopic ears" filled the complete
      anterior region of the embryos. The ectopic induction of otic development can be
      explained by the juxtaposition of hindbrain tissue with anterior ectoderm.
      Fibroblast growth factor (Fgf) ligands are thought to mediate the otic-inducing
      properties of the hindbrain. However, signals different from Fgf3 and Fgf8 are
      necessary to explain the formation of the ectopic ear structures, suggesting that
      Wnt signalling is involved in the otic induction process in medaka.

PMID- 19760183
TI  - A conserved function of the zinc finger transcription factor Sp8/9 in allometric
      appendage growth in the milkweed bug Oncopeltus fasciatus.
AB  - The genes encoding the closely related zinc finger transcription factors
      Buttonhead (Btd) and D-Sp1 are expressed in the developing limb primordia of
      Drosophila melanogaster and are required for normal growth of the legs. The D-Sp1
      homolog of the red flour beetle Tribolium castaneum, Sp8 (appropriately termed
      Sp8/9), is also required for the proper growth of the leg segments. Here we
      report on the isolation and functional study of the Sp8/9 gene from the milkweed
      bug Oncopeltus fasciatus. We show that Sp8/9 is expressed in the developing
      appendages throughout development and that the downregulation of Sp8/9 via RNAi
      leads to antennae, rostrum, and legs with shortened and fused segments. This
      supports a conserved role of Sp8/9 in allometric leg segment growth. However, all
      leg segments including the claws are present and the expression of the leg genes
      Distal-less, dachshund, and homothorax are proportionally normal, thus providing
      no evidence for a role of Sp8/9 in appendage specification.

PMID- 19760185
TI  - Profiling of dynamics in protein-lipid-water systems: a time-resolved
      fluorescence study of a model membrane protein with the label BADAN at specific
      membrane depths.
AB  - Profiles of lipid-water bilayer dynamics were determined from picosecond time
      resolved fluorescence spectra of membrane-embedded BADAN-labeled M13 coat
      protein. For this purpose, the protein was labeled at seven key positions. This
      places the label at well-defined locations from the water phase to the center of
      the hydrophobic acyl chain region of a phospholipid model membrane, providing us
      with a nanoscale ruler to map membranes. Analysis of the time-resolved
      fluorescence spectroscopic data provides the characteristic time constant for the
      twisting motion of the BADAN label, which is sensitive to the local flexibility
      of the protein-lipid environment. In addition, we obtain information about the
      mobility of water molecules at the membrane-water interface. The results provide
      an unprecedented nanoscale profiling of the dynamics and distribution of water in
      membrane systems. This information gives clear evidence that the actual barrier
      of membranes for ions and aqueous solvents is located at the region of carbonyl
      groups of the acyl chains.

PMID- 19760186
TI  - Application of uterotonics on the basis of regular ultrasonic evaluation of the
      uterus prevents unnecessary surgical intervention in the postpartum period.
AB  - OBJECTIVE: Ultrasonographic evaluation of the postpartum uterus to prevent
      retained placental tissue complications is still a matter of debate, and it is
      difficult to interpret its necessity on the basis of previous studies. We
      hypothesized that the application of uterotonics on the basis of regular
      postpartum ultrasound scanning of the uterus may reduce the number of unnecessary
      curettages in a large unselected population. METHODS: This was a cross-sectional
      observational study conducted among mothers (n = 6,028) delivering at two
      different (secondary and tertiary) hospitals to analyze the benefit of postpartum
      uterine ultrasound for clinical implications. Women delivering at the secondary
      care unit (n = 1,915) had no regular postpartum ultrasound scans in comparison to
      those delivering at the tertiary unit (n = 4,113). On regular ultrasound scans,
      morphological findings in the uterine cavity were recorded. Upon the presence of
      an intrauterine hyperechogenic mass larger than 2 cm in diameter, mothers
      received a single dose of uterotonics (methylergometrin 0.2 mg or oxytocin 5 IU)
      intramuscularly and control sonography after 24 h. In case of intrauterine mass
      persistence and serious postpartum hemorrhage women underwent a surgical
      intervention. The management was similar at the secondary unit, but ultrasound
      scans were provided only when there was a clinical finding. All patients were
      followed-up 6 weeks after labor. RESULTS: Women delivering at the secondary
      institution experienced a higher incidence of puerperal surgical interventions
      (1.51 vs. 0.87%) and lower agreement between sonography and histological findings
      (72.4 vs. 86.1%) compared with women delivering at the tertiary care unit,
      respectively (P < 0.05), where the general incidence of interventions was 1.10%
      after spontaneous and 0.19% after cesarean deliveries. In addition, trained
      sonographers reached only 13.9% false-positive ultrasound scans. Time-dependent
      regression analysis of uterine morphological involution variables showed a
      significant association between uterine length, width, uterine cavity and
      cervical channel mass, P < 0.0001, P < 0.01, P < 0.05, P < 0.05, respectively,
      and insignificant association between uterine cavity volume with an increased
      time period postpartum. CONCLUSIONS: In this study, routine ultrasound evaluation
      of the uterus in the postpartum period with regular application of uterotonics
      decreased the rate of surgical interventions. We strongly advise the introduction
      of postpartum uterine scanning into obstetrical practice, most suitably provided
      around day 3 after delivery.

PMID- 19760187
TI  - The relationship between serum Chlamydia antibody levels and severity of disease
      in infertile women with tubal damage.
AB  - BACKGROUND: The study explores the relationship between serum Chlamydia antibody
      titres (CAT) using the whole-cell inclusion immunofluorescence (WIF) test and
      severity of tubal damage in infertile women undergoing laparoscopy. METHODS:
      Comparisons between the extent of specific lesions, including their severity
      found at laparoscopy, and CAT levels were analysed in 408 infertile women with
      tubal damage. CAT levels were assayed using the WIF test. RESULTS: There were
      significant differences in the severity of individual lesions (tubal occlusion,
      tubal pathology, fimbrial state, extent and type of tubal and ovarian adhesions,
      type of tubal and ovarian adhesions) for both left and right adnexa in relation
      to CAT (P < 0.0001). The presence and severity of lesions found in one adnexum
      significantly correlated with the findings on the contra-lateral side (r > 0.5; P
      < 0.01). The American Fertility Society grades for tubal occlusion and adhesions
      in the right adnexum did not correlate with CAT. CONCLUSIONS: CAT levels are
      quantitatively related to the severity of tubal damage in infertile women. Wide
      variations in the severity of lesions observed in relation to CAT were suggestive
      of broad individual differences in response to chlamydial infection.

PMID- 19760188
TI  - Cyclic stretch downregulates arterial vascular connexin43 protein expression: an
      ex vivo study.
AB  - Vascular cells may communicate through gap junctions that are formed by connexin
      (Cx) proteins. We investigated differential regulation of arterial gap junctions
      by steady and cyclic stretch and the underlying mechanotransduction pathways. Ex
      vivo culture of rabbit thoracic aortas was used to investigate regulation of Cx43
      by cyclic stretch. After culturing for 6 or 24 h, Cx43 protein levels were
      quantified using Western blot. Cultures under a pulsatile pressure (mean 80 mmHg,
      pulse 30 mmHg) decreased Cx43 protein at both 6 and 24 h as compared with
      cultures under a steady pressure (80 mmHg). The regulation of Cx43 protein was
      mediated by pulsatile pressure-induced cyclic stretch, not by cyclic stress.
      Protein levels of active and total Src were also decreased by cyclic stretch at
      24 h. The Src- specific inhibitor PP1 in steady culture only or in both steady
      and pulsatile culture conditions eliminated the difference in Cx43 protein levels
      between the two culture conditions. Addition of reactive oxygen species inhibitor
      apocynin to the pulsatile culture abolished the differences in Src and Cx43
      protein levels between the two cultures. Thus, Src and reactive oxygen species
      appear to play a role in cyclic stretch-mediated regulation of Cx43 protein.
      These results are likely to have important implications in cardiovascular
      physiology and pathophysiology under conditions wherein significant alterations
      in the level of cyclic stretch are present.

PMID- 19760189
TI  - Evaluation of the oxidative status of virgin olive oils with different phenolic
      content by direct infusion atmospheric pressure chemical ionization mass
      spectrometry.
AB  - Atmospheric pressure chemical ionization mass spectrometry was used to predict
      the oxidative status of virgin olive oils (VOO) during their storage. VOO
      samples, with and without phenolic compounds, were stored in the dark at 60
      degrees C up to 7 weeks. The VOO samples were diluted in an alkaline
      propanol/methanol mixture and directly infused into an ion-trap mass
      spectrometer. The abundances of the [M-H](-) peaks of free fatty acids, oxidized
      fatty acids, tocopherols and phenolic compounds, jointly with their oxidized
      forms, were measured and used as predictors. Two linear discriminant analysis
      (LDA) models were constructed in order to classify samples according to their
      oxidative levels. The first model was constructed using both VOO samples (with
      and without phenols), considering as predictors only fatty acids and their
      oxidized products. The second LDA model was constructed with the VOO sample with
      phenolic compounds considering as predictors all the peaks measured. In both
      models, the samples divided in the eight different storage times were correctly
      classified (100%) by leave-one-out cross-validation with an excellent resolution
      among all the category pairs (for the first model Wilks' lambda, lambda(w) =
      0.229 and for the second lambda(w) = 0.928). This method is a very fast tool for
      on-line monitoring of VOO oxidation status.

PMID- 19760190
TI  - Non-invasive identification of organic materials in wall paintings by fiber optic
      reflectance infrared spectroscopy: a statistical multivariate approach.
AB  - The aim of this study is to develop a method for the non-invasive and in situ
      identification of organic binders in wall paintings by fiber optic mid-FTIR
      reflectance spectroscopy. The non-invasive point analysis methodology was set-up
      working on a wide set of wall painting replicas of known composition and using
      statistical multivariate methods, in particular principal component analysis
      (PCA), for the interpretation, understanding, and management of data acquired
      with reflectance mid-FTIR spectroscopy. Results show that PCA can be helpful in
      managing and preliminary sorting of the large amount of spectra typically
      collected during non-invasive measurement campaigns and highlight further avenues
      for research. The developed PCA model was finally applied to the case of a
      Renaissance wall painting by Perugino assessing it predictability as compared to
      the interpretation of the single spectrum.

PMID- 19760191
TI  - Quantitative determination of Phakellistatin 13, a new cyclic heptapeptide, in
      rat plasma by liquid chromatography/tandem mass spectrometry: application to a
      pharmacokinetic study.
AB  - A sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method,
      followed by a 96-well protein precipitation, has been developed and fully
      validated for the determination of Phakellistatin 13 (PK13), a new cyclic
      heptapeptide isolated from the sponge Phakellia fusca Thiele, in rat plasma.
      After protein precipitation of the plasma samples (50 microL) in a 96-well plate
      by methanol (200 microL) containing the internal standard Pseudostellarin B (20
      ng/mL), the plate was vortex mixed for 3 min. Following filtration for 5 min, the
      filtrate was directly injected into the LC-MS/MS system. The analytes were
      separated on an XB-C18 analytical column (5 microm, 50 mm x 4.6 mm i.d.) using an
      eluent of methanol-water (85:15, v/v) and detected by electrospray ionization
      mass spectrometry in the negative multiple reaction monitoring mode with a
      chromatographic run time of 5.0 min. The method was sensitive with a lower limit
      of quantification (LLOQ) of 0.1 ng/mL, with good linearity (r > 0.999) over the
      quantitation range of 0.1-5 ng/mL. The validation results demonstrated that this
      method was significantly specific, accurate, precise, and was successfully
      applied in measuring levels of PK13 in rat plasma following intravenous
      administration of 20, 50, and 100 microg/kg of peptide in rats, respectively,
      which was suitable for the preclinical pharmacokinetic studies on PK13.

PMID- 19760192
TI  - Study on the impregnation of archaeological waterlogged wood with consolidation
      treatments using synchrotron radiation microtomography.
AB  - In favourable conditions of low temperature and low oxygen concentration,
      archaeological waterlogged wooden artefacts, such as shipwrecks, can survive with
      a good state of preservation. Nevertheless, anaerobic bacteria can considerably
      degrade waterlogged wooden objects with a significant loss in polysaccharidic
      components. Due to these decay processes, wood porosity and water content
      increase under ageing. In such conditions, the conservation treatments of
      archaeological wooden artefacts often involve the replacement of water with
      substances which fill the cavities and help to prevent collapse and stress during
      drying. The treatments are very often expensive and technically difficult, and
      their effectiveness very much depends on the chemical and physical
      characteristics of the substances used for impregnation. Also important are the
      degree of cavity-filling, penetration depth and distribution in the structure of
      the wood. In this study, the distribution in wood cavities of some mixtures based
      on polyethylene glycols and colophony, used for the conservation of waterlogged
      archaeological wood, was investigated using synchrotron radiation X-ray computed
      microtomography (SR-microCT). This non-destructive imaging technique was useful
      for the study of the degraded waterlogged wood and enabled us to visualise the
      morphology of the wood and the distribution of the materials used in the wood
      treatments. The study has shown how deposition is strictly related to the
      dimension of the wooden cavities. The work is currently proceeding with the
      comparison of synchrotron observations with the data of the solutions viscosity
      and with those of the properties imparted to the wood by the treatments.

PMID- 19760193
TI  - Analysis of selected phytotoxins and mycotoxins in environmental samples.
AB  - Natural toxins such as phytotoxins and mycotoxins have been studied in food and
      feed for decades, but little attention has yet been paid to their occurrence in
      the environment. Because of increasing awareness of the presence and potential
      relevance of micropollutants in the environment, phytotoxins and mycotoxins
      should be considered and investigated as part of the chemical cocktail in natural
      samples. Here, we compile chemical analytical methods to determine important
      phytotoxins (i.e. phenolic acids, quinones, benzoxazinones, terpenoids,
      glycoalkaloids, glucosinolates, isothiocyanates, phytosterols, flavonoids,
      coumestans, lignans, and chalcones) and mycotoxins (i.e. resorcyclic acid
      lactones, trichothecenes, fumonisins, and aflatoxins) in environmentally relevant
      matrices such as surface water, waste water-treatment plant influent and
      effluent, soil, sediment, manure, and sewage sludge. The main problems
      encountered in many of the reviewed methods were the frequent unavailability of
      suitable internal standards (especially isotope-labelled analogues) and often
      absent or fragmentary method optimization and validation.

PMID- 19760194
TI  - Lenalidomide in patients with cisplatin-refractory and multiply relapsed germ
      cell tumors.
AB  - OBJECTIVE: Treatment options are still limited in patients with cisplatin
      refractory and multiply relapsed germ cell tumors. We evaluated the efficacy and
      tolerability of lenalidomide within a compassionate use concept. PATIENTS AND
      METHODS: Four patients multiply relapsed after platin-based chemotherapies
      without any further standard treatment option received 25 mg lenalidomide orally
      on days 1-21 of a 28-day cycle. RESULTS: All four patients were pretreated with a
      median number of seven lines of previous chemotherapy (range 4-8), all including
      platin-based high-dose chemotherapy. After 4 weeks of lenalidomide treatment all
      patients had progressive disease with increase in serum tumor markers and
      progression in computed tomography. Median survival time was 8 weeks (range 5
      17). The toxicity profile was favorable. No severe toxicities related to
      lenalidomide occurred in these patients. CONCLUSION: Lenalidomide was well
      tolerated but did not show efficacy in heavily pretreated patients with cisplatin
      refractory and multiply relapsed germ cell tumors.

PMID- 19760195
TI  - Hypoxia induced paclitaxel resistance in human ovarian cancers via hypoxia
      inducible factor 1alpha.
AB  - PURPOSE: Chemoresistance severely restricts the anti-cancer medicines from
      effectively treating human ovarian cancer, which has been shown to develop and
      survive in the specific hypoxic environments. To understand the relationship
      between hypoxia and chemoresistance, we investigated the potential role of
      hypoxia in the pathophysiology of chemoresistance, especially focusing on hypoxia
      inducible factor 1alpha (HIF-1alpha). METHODS: The A2780 ovarian cancer cells are
      cultured in gradient hypoxic conditions (5% O(2), 3% O(2), and 1% O(2)), the
      sensitivity of the cells to paclitaxel and the cell inhibitory rate were
      determined by MTT assay. The expression and the transcriptional activity of HIF
      1alpha were examined by western blot, Immunocytochemical staining, reverse
      transcription-polymerase chain reaction (RT-PCR), and the dual luciferase
      reporter system, respectively. The cell cycle distribution was analyzed by flow
      cytometry. In addition, we silence HIF-1alpha expression by performing RNA
      interference. RESULTS: MTT assay demonstrates that hypoxic challenge
      substantially reduces the susceptibility of cells to paclitaxel at all the tested
      concentrations. Coincident with this is the activation of HIF-1alpha in nuclear,
      which displays the increased transcriptional activity and high protein
      expression. Hypoxic manipulation (5% O(2), approximately 1% O(2)) significantly
      increased the cell population at G0/G1. Interestingly, knockdown of endogenous
      HIF-1alpha significantly alleviates the chemoresistance and promotes G1/S
      transition with the increased sensitivity of A2780 cells to paclitaxel under each
      hypoxic condition. CONCLUSIONS: It suggests that HIF-1alpha, stimulated by
      hypoxia, exerts a pivotal role in chemoresistance by G0/G1 arrest. Eliminating
      hypoxic conditions or silencing HIF-1alpha by siRNA might provide a potent tool
      to enhance paclitaxel effectiveness in treatment of human ovarian cancer.

PMID- 19760196
TI  - Adenocarcinoma of the small bowel at a single Korean institute: management and
      prognosticators.
AB  - PURPOSE: Small bowel adenocarcinoma (SBA) is a rare malignancy with a poor
      outcome. We evaluated the natural history of SBA at a single Korean institute.
      METHODS: Medical records of 100 patients with SBA were reviewed for clinical
      characteristics, treatment patterns, outcomes, and prognostic factors. RESULTS:
      The most common primary tumor site was the duodenum (82%). Seventy-four patients
      were diagnosed with stage III/IV disease (28/46 patients, respectively). Sixty
      six patients had surgery (R0/R1/R2 in 32/2/32) without operation-related
      mortality. Of 34 R0/R1-resected patients, 16 received adjuvant chemotherapy. The
      dominant pattern of recurrence following R0/R1 resection was distant metastasis
      (29%; 10 of 34 patients). Thirty-four patients with advanced SBA received
      palliative chemotherapy, showing a response rate of 27.6% and a median
      progression-free survival of 3.8 months. The median overall survival for all
      patients and R0/R1-resected patients was 10.5 and 42.1 months, respectively. In
      multivariate analysis, lower stage, nonduodenal location, and R0/R1 resection
      were good independent prognostic factors. CONCLUSIONS: Early diagnosis is crucial
      to improve outcomes of SBA with respect to increasing resectability. Distant
      metastasis as a dominant pattern of recurrence suggests a potential role for
      adjuvant chemotherapy. Newer antitumor agents in advanced SBA should be evaluated
      considering the poor efficacy of current palliative chemotherapy.

PMID- 19760197
TI  - Intestinal ascariasis: the commonest cause of bowel obstruction in children at a
      tertiary care center in Kashmir.
AB  - BACKGROUND: Ascariasis is the commonest intestinal nematodal infestation in man.
      Ascariasis commonly inhabits small bowel although it can migrate to biliary tree
      and other orifices. The aim of this study is to analyze the presentation,
      diagnosis, management of bowel obstruction caused by Ascaris lumbricoides and to
      study various surgical complications. MATERIALS AND METHODS: All patients, 3-14
      years of age, who attended the emergency department with diagnosis of intestinal
      obstruction were screened. Out of these patients with diagnosis of ascariasis
      based on history of passage of worms per mouth or rectum, X-ray or
      ultrasonography were followed for a minimum of 6 months. Data regarding the type
      of management, operative findings, operative procedure and post-operative
      complications were noted. RESULT: Out of 207 patients who were admitted with the
      diagnosis of intestinal obstruction, 131 were diagnosed as having obstruction due
      to ascariasis. Most of the patients were 3-5 years of age. Males and females were
      equally affected. 64 patients needed an operative intervention. Enterotomy was
      the commonest procedure followed by milking of worms and resection anastomosis.
      Appendicular perforation was seen in four and worm in gall bladder in one
      patient. Surgical complications were wound infection in 17, burst abdomen in four
      and fecal fistula in three patients. CONCLUSION: Round worm obstruction should be
      considered as the first differential diagnosis in any patient of intestinal
      obstruction in an endemic area like ours. Although most cases are managed
      conservatively, many patients still need surgical intervention. Efforts should be
      made toward eradication of this disease by proper sanitation, hygiene and the use
      of antihelminthics.

PMID- 19760198
TI  - Sutureless skin closure with isoamyl 2-cyanoacrylate in pediatric day-care
      surgery.
AB  - Importance of day-care surgery in pediatric age group is ever increasing and
      nowadays bulk of surgery is performed as a day-care procedure. Day-care procedure
      requires short intra-operative period and less postoperative complications. The
      introduction of tissue adhesive has been received enthusiastically since they may
      result in equivalent tensile strength-improved cosmetic appearance of the scar
      and lower infection rate when compared to sutures, staples and adhesive tape. We
      have used isoamyl 2-cyanoacrylate as a tissue adhesive for skin closure in day
      care surgery. Novocryl is ideal for such procedure as it is a sterile, inert, non
      toxic, biocompatible and bacteriostatic liquid topical skin adhesive containing
      isoamyl 2-cyanoacrylate formulation. We applied isoamyl 2-cyanoacrylate glue in
      100 patients over skin cut margin after stitching subcutaneous tissue. Skin
      margin were held together by means of skin hook for 1-2 min. The cosmesis was
      better as there were no suture marks or lumpiness. There were no major
      complications in our study. Thus, isoamyl 2-cyanoacrylate can be considered as an
      alternative to skin suturing in the pediatric day-care surgery.

PMID- 19760199
TI  - New insights into the pathogenesis of infantile pyloric stenosis.
AB  - Infantile hypertrophic pyloric stenosis (IHPS) is the most common surgical cause
      of vomiting in infants. Despite numerous hypotheses, the aetiopathogenesis of
      IHPS is not fully understood. Genetic, extrinsic and hormonal factors have been
      implicated in the pathogenesis of the disease. Furthermore, abnormalities of
      various components of the pyloric muscle such as smooth muscle cells, growth
      factors, extracellular matrix elements, nerve and ganglion cells, synapses, nerve
      supporting cells, neurotransmitters and interstitial cells of Cajal have been
      reported. Recently, genetic studies have identified susceptibility loci for IHPS
      and molecular studies have concluded that smooth muscle cells are not properly
      innervated in IHPS.

PMID- 19760200
TI  - The protective effect of erythropoietin on the acute phase of corrosive
      esophageal burns in a rat model.
AB  - INTRODUCTION: An experimental study was conducted to investigate the effects of
      erythropoietin on the acute phase of esophageal burn damage induced by sodium
      hydroxide. MATERIALS AND METHODS: A standard esophageal alkaline burn was
      produced by the application of 10% sodium hydroxide to the distal esophagus in an
      in vivo rat model. Fifty-six female rats were allocated into three groups: Group
      BC (baseline control, n = 8) rats were uninjured and untreated, Group PC
      (positive control, n = 24) rats were injured but untreated and Group EPO
      (erythropoietin-treated, n = 24) rats were injured and given subcutaneous
      erythropoietin (1,000 IU/kg per day), 15 min, 24, and 48 h after administration
      of the NaOH solution. Six animals from Group PC and six from Group EPO were
      killed at 4, 24, 48, and 72 h after application of NaOH to the esophagus. All of
      animals in Group BC were killed 4 h after exposure to 0.9% NaCl. Oxidative damage
      was assessed by measuring levels of malondialdehyde (MDA) and nitric oxide (NO),
      and activities of superoxide dismutase (SOD) and catalase (CAT) in homogenized
      samples of esophageal tissue. Histologic damage to esophageal tissue was scored
      by a single pathologist blind to groups. RESULTS: MDA levels in the BC and EPO
      groups were significantly lower than those in the PC group (p < 0.05). CAT and
      SOD activities, and NO levels in the BC and EPO groups were significantly higher
      than in the PC group (p < 0.05). Esophageal tissue damage measured at 4, 24, 48,
      and 72 h after NaOH application was significantly less in the EPO group than in
      the PC group (p < 0.05). CONCLUSIONS: When administered early after an esophageal
      burn induced by 10% sodium hydroxide in this rat model, erythropoietin
      significantly attenuated oxidative damage, as measured by biochemical markers and
      histologic scoring.

PMID- 19760201
TI  - Ciliated hepatic foregut cysts in children.
AB  - Ciliated hepatic foregut cyst (CHFC) is a rare foregut developmental malformation
      usually diagnosed in adulthood; however, rare cases have been reported in the
      pediatric population. CHFC can transform into a squamous cell carcinoma resulting
      in death despite surgical resection of the isolated malignancy. We report the
      presentation, evaluation, and surgical management of a symptomatic 17-year-old
      girl found to have a 6.5 x 4.5 cm CHFC and suggest that all patients with
      suspected CHFC undergo prompt evaluation and complete cyst excision.

PMID- 19760202
TI  - Patented natural avocado sugars modulate the HBD-2 expression in human
      keratinocytes through the involvement of protein kinase C and protein tyrosine
      kinases.
AB  - Skin keratinocytes constitute a protective mechanical barrier against invading
      microorganisms. Stimulated keratinocytes produce endogenous peptides such as the
      beta-defensins that have direct antimicrobial activity against a broad spectrum
      of pathogens, including most bacteria, certain fungi and enveloped viruses. In
      particular, human beta-defensin 2 (HBD-2) is virtually absent in normal skin and
      its expression in human keratinocytes requires stimulation by cytokines or
      bacteria. AV119, a patented avocado sugar, triggers the up-regulation of HBD-2,
      but the signalling mechanisms involved in this up-regulation in stimulated
      keratinocytes are not fully understood. In the present study, we examined the
      intracellular signalling pathways and nuclear responses in skin keratinocytes
      that contribute to HBD-2 gene expression upon stimulation with AV119. Our data
      provide information on signalling pathways in which the activation of protein
      tyrosine kinases (PTKs) and protein kinase C (PKC) takes place and leads to AP-1
      and HBD-2 gene activation.

PMID- 19760203
TI  - Determinants of regional ventilation and blood flow in the lung.
AB  - The principles of ventilation and perfusion distribution in the lung form the
      foundation of pulmonary physiology and remain cornerstones in caring for
      critically ill patients. Due to improved imaging technologies with greater
      spatial resolution, our understanding of the determinants of local ventilation
      and blood flow have evolved over the past five decades. This review provides a
      brief history of how the concepts governing regional ventilation and perfusion
      have developed and presents the most recent studies that are shaping new
      perspectives on the determinants of ventilation and perfusion. How these new
      principles apply to acute lung injury and gas exchange in the intensive care
      unit(ICU) are reviewed.

PMID- 19760204
TI  - Usefulness of a clinical diagnosis of ICU-acquired paresis to predict outcome in
      patients with SIRS and acute respiratory failure.
AB  - PURPOSE: Neuromuscular abnormalities are common in ICU patients. We aimed to
      assess the incidence of clinically diagnosed ICU-acquired paresis (ICUAP) and its
      impact on outcome. METHODS: Forty-two patients with systemic inflammatory
      response syndrome on mechanical ventilation for >or=48 h were prospectively
      studied. Diagnosis of ICUAP was defined as symmetric limb muscle weakness in at
      least two muscle groups at ICU discharge without other explanation. The threshold
      Medical Research Council (MRC) Score was set at 35 (of 50) points. Activities in
      daily living were scored using the Barthel Index 28 and 180 days after ICU
      discharge. RESULTS: Three patients died before sedation was stopped. ICUAP was
      diagnosed in 13 of the 39 patients (33%). Multivariate regression analysis
      yielded five ICUAP-predicting variables (P < 0.05): SAPS II at ICU admission,
      treatment with steroids, muscle relaxants or norepinephrine, and days with
      sepsis. Patients with ICUAP had lower admission SAPS II scores [37 +/- 13 vs. 49
      +/- 15 (P = 0.018)], lower Barthel Index at 28 days and lower survival at 180
      days after ICU discharge (38 vs. 77%, P = 0.033) than patients without ICUAP.
      Daily TISS-28 scores were similar but cumulative TISS-28 scores were higher in
      patients with ICUAP (664 +/- 275) than in patients without ICUAP (417 +/- 236; P
      = 0.008). The only independent risk factor for death before day 180 was the
      presence of ICUAP. CONCLUSIONS: A clinical diagnosis of ICUAP was frequently
      established in this patient group. Despite lower SAPS II scores, these patients
      needed more resources and had high mortality and prolonged recovery periods after
      ICU discharge.

PMID- 19760205
TI  - A multiparameter panel method for outcome prediction following aneurysmal
      subarachnoid hemorrhage.
AB  - PURPOSE: Accurate early anticipation of long-term irreversible brain damage
      during the acute phase of patients with aneurysmal subarachnoid hemorrhage (aSAH)
      remains difficult. Using a combination of clinical scores together with brain
      injury-related biomarkers (H-FABP, NDKA, UFD1 and S100beta), this study aimed at
      developing a multiparameter prognostic panel to facilitate early outcome
      prediction following aSAH. METHODS: Blood samples of 141 aSAH patients from two
      separated cohorts (sets of 28 and 113 patients) were prospectively enrolled and
      analyzed with 14 months of delay. Patients were admitted within 48 h following
      aSAH onset. A venous blood sample was withdrawn within 12 h after admission. H
      FABP, NDKA, UFD1, S100beta and troponin I levels were determined using classical
      immunoassays. The World Federation of Neurological Surgeons (WFNS) at admission
      and the Glasgow Outcome Score (GOS) at 6 months were evaluated. RESULTS: In the
      two cohorts, blood concentration of H-FABP, S100beta and troponin I at admission
      significantly predicted unfavorable outcome (GOS 1-2-3). A multivariate analysis
      identified a six-parameter panel, including WFNS, H-FABP, S100beta, troponin I,
      NDKA and UFD-1; when at least three of these parameters were simultaneously above
      cutoff values, prediction of unfavorable outcome reached around 70% sensitivity
      in both cohorts for 100% specificity. CONCLUSION: The use of this panel,
      including four brain injury-related proteins, one cardiac marker and a clinical
      score, could be a valuable tool to identify aSAH patients at risk of poor
      outcome.

PMID- 19760206
TI  - Reducing in-hospital cardiac arrests and hospital mortality by introducing a
      medical emergency team.
AB  - PURPOSE: To prospectively evaluate the implementation of a rapid response team in
      the form of a medical emergency team (MET) with regard to cardiac arrests and
      hospital mortality. METHODS: Prospective before-and-after trial of implementation
      of a MET at the Karolinska University Hospital, Stockholm, Sweden. All adult
      patients, apart from cardiothoracic, admitted to the hospital were regarded as
      participants in the study. A control period of 5 years and 203,892 patients
      preceded the 2-year intervention period of 73,825 patients. MAIN RESULTS: Number
      of MET calls was 9.3 per 1,000 hospital admissions. Cardiac arrests per 1,000
      admissions decreased from 1.12 to 0.83, OR 0.74 (95% CI 0.55-0.98, p = 0.035).
      Adjusted for age, sex, hospital length of stay, acute/elective admission as well
      as co-morbidities, MET implementation was associated with a reduction in total
      hospital mortality by 10%, OR 0.90 (95% CI 0.84-0.97), p = 0.003. Hospital
      mortality was also reduced for medical patients by 12%, OR 0.88 (95% CI 0.81
      0.96, p = 0.002) and for surgical patients not operated upon by 28%, OR 0.72 (95%
      CI 0.56-0.92, p = 0.008). FOR PATIENTS FULFILLING THE MET CRITERIA: Thirty-day
      mortality pre-MET was 25% versus 7.9% following MET compared with historical
      controls. Similarly, 180-day mortality was 37.5% versus 15.8%, respectively.
      CONCLUSIONS: Implementing the MET team was associated with significant
      improvement in both cardiac arrest rate and overall adjusted hospital mortality.
      Significant reductions in hospital mortality for un-operated surgical patients as
      well as for medical patients were also seen. Thus, introduction of the MET seemed
      to improve outcome for hospitalized patients.

PMID- 19760207
TI  - Tidal volume during acute lung injury:  let the patient choose?

PMID- 19760208
TI  - Multicenter comparison of cortisol as measured by different methods in samples of
      patients with septic shock.
AB  - PURPOSE: To compare inter-laboratory and inter-assay measurements of total
      cortisol in patients with septic shock and to evaluate current recommendations
      for diagnosis of corticosteroid insufficiency in septic shock. METHODS: In the
      multinational CORTICUS study duplicate serum samples were taken before and after
      corticotropin stimulation tests in patients with septic shock. Serum cortisol was
      measured in paired samples, one being measured by the chemical laboratory of each
      participating site and the other by a central laboratory using an
      electrochemiluminescence immunoassay. Cortisol levels measured by tandem mass
      spectrometry were used as a 'gold standard' reference method in a subset of
      samples. RESULTS: A total of 425 corticotropin tests (850 cortisol samples) were
      available for comparison of local and central laboratory measurements. The
      concordance correlation coefficient between central laboratory immunoassay and
      local hospital assays was 0.98 (CI 0.97-0.99) when the immunoassay of one
      manufacturer was used and 0.60 (CI 0.54-0.65) when immunoassays of different
      manufacturers were used. The comparison with the reference method of mass
      spectrometry showed concordance correlation coefficients ranging from 0.43 to
      0.97 depending on the assay under study. Diagnosis of corticosteroid
      insufficiency was diverging due to inter-assay variations in up to 27% of cases.
      CONCLUSION: In samples taken from patients in septic shock, there was a high
      inter-assay variation of total serum cortisol. Comparisons with a reference
      method revealed both over- and underestimations of true cortisol levels. These
      inter-assay variations in samples of patients with septic shock complicate the
      diagnosis of corticosteroid insufficiency.

PMID- 19760209
TI  - Neurally adjusted ventilatory assist decreases  ventilator-induced lung injury 
      and non-pulmonary organ dysfunction  in rabbits with acute lung injury.
AB  - OBJECTIVE: To determine if neurally adjusted ventilatory assist (NAVA) that
      delivers pressure in proportion to diaphragm electrical activity is as protective
      to acutely injured lungs (ALI) and non-pulmonary organs as volume controlled
      (VC), low tidal volume (Vt), high positive end-expiratory pressure (PEEP)
      ventilation. DESIGN: Prospective, randomized, laboratory animal study. SUBJECTS:
      Twenty-seven male New Zealand white rabbits. INTERVENTIONS: Anesthetized rabbits
      with hydrochloric acid-induced ALI were randomized (n = 9 per group) to 5.5 h
      NAVA (non-paralyzed), VC (paralyzed; Vt 6-ml/kg), or VC (paralyzed; Vt 15-ml/kg).
      PEEP was adjusted to hemodynamic goals in NAVA and VC6-ml/kg, and was 1 cmH2O in
      VC15-ml/kg. MEASUREMENTS AND MAIN RESULTS: PaO2/FiO2; lung wet-to-dry ratio; lung
      histology; interleukin-8 (IL-8) concentrations in broncho-alveolar-lavage (BAL)
      fluid, plasma, and non-pulmonary organs; plasminogen activator inhibitor type-1
      and tissue factor in BAL fluid and plasma; non-pulmonary organ apoptosis rate;
      creatinine clearance; echocardiography. PEEP was similar in NAVA and VC6-ml/kg.
      During NAVA, Vt was lower (3.1 +/- 0.9 ml/kg), whereas PaO2/ FiO2, respiratory
      rate, and PaCO2 were higher compared to VC6-ml/kg (p<0.05 for all). Variables
      assessing ventilator-induced lung injury (VILI), IL-8 levels, non-pulmonary organ
      apoptosis rate, and kidney as well as cardiac performance were similar in NAVA
      compared to VC6-ml/kg. VILI and non-pulmonary organ dysfunction was attenuated in
      both groups compared to VC15-ml/kg. CONCLUSIONS: In anesthetized rabbits with
      early experimental ALI, NAVA is as effective as VC6-ml/kg in preventing VILI, in
      attenuating excessive systemic and remote organ inflammation, and in preserving
      cardiac and kidney function.

PMID- 19760210
TI  - Serum procalcitonin levels in critically ill patients colonized with Candida spp:
      new clues for the early recognition of invasive candidiasis?
AB  - OBJECTIVE: Invasive candidiasis (IC) outcomes in intensive care units (ICUs)
      could be improved by the early administration of antifungals. The Candida Score
      (CS) prediction rule has been proposed for the selection of patients who could
      develop IC. Procalcitonin (PCT) levels allow prompt identification of sepsis, but
      their behavior in the setting of IC is unclear. We hypothesize that PCT could be
      helpful in the early diagnosis of IC in patients with Candida sp. colonization.
      DESIGN: Prospective observational study. SETTING: Thirty-six ICUs in Spain,
      Portugal and France. PATIENTS: Every non-neutropenic critically ill patient
      hospitalized for more than 7 days without concurrent bacterial infection. The CS
      was calculated weekly. Serums were collected concomitantly. MEASUREMENTS AND
      RESULTS: Two hundred twenty PCT levels were measured in 136 patients [neither
      colonized nor infected (NCNI): n = 73; multifocal colonization (MF): n = 43; MF +
      IC: n = 20]. Baseline PCT levels were significantly higher in the MF + IC group
      than in other groups (p = 0.001). In patients with MF, the highest CS value
      calculated during the patient's stay was the sole independent predictor of IC.
      The receiver-operating curve analysis showed that the diagnosis values of PCT and
      CS were comparable (AUROCC = 0.713, and 0.727, respectively). Moreover, PCT
      increased the positive predictive value of CS from 44.7 to 59.3%. CONCLUSIONS:
      After 7 days of hospitalization, PCT levels in patients with MF who go on to
      develop IC are higher than in others. Serum PCT could also improve the predictive
      value of CS. PCT together with CS could therefore be considered for the
      assessment of IC risk.

PMID- 19760211
TI  - Identification of polymorphisms in the RNase3 gene and the association with
      allergic rhinitis.
AB  - Eosinophil cationic protein (ECP), a potent cytotoxic molecule, is released by
      activated eosinophils. ECP has been suggested to be involved in tissue remodeling
      of allergic diseases. The ECP (RNase3) gene is a candidate gene in atopic
      diseases. RNase3 polymorphisms have been reported to have an association with
      atopy. We determined whether polymorphisms in the RNase3 gene are associated with
      allergic rhinitis in a Korean population. The Taqman assay, restriction fragment
      length polymorphism (PCR-RFLP), and high-resolution melt (HRM) were used for
      genotyping. Three single nucleotide polymorphisms (SNPs; g.-550A>G, g.371G>C, and
      g.499G>C) were identified. The genotype of the SNPs was analyzed in patients with
      allergic rhinitis and controls without allergic rhinitis. The genotype and allele
      frequencies were compared between both groups. The genotype frequencies of the g.
      550A>G and g.371G>C SNPs were not significantly different between patients with
      allergic rhinitis and controls (P > 0.05). However, in patients with allergic
      rhinitis, the genotype and allele frequencies of the g.499G>C SNP of RNase 3 were
      significantly different from those of the control group (P < 001, P = 0.034,
      respectively). Haplotype analysis demonstrated the presence of the following five
      different (-550)-(+371)-(+499) major haplotypes: A-G-G, G-C-C, G-G-G, G-C-G, and
      A-G-C. The G-C-G haplotype was positively associated with allergic rhinitis (P =
      0.048), while the G-G-G haplotype was negatively associated with allergic
      rhinitis (P = 0.004). Our study suggests that RNase3 polymorphisms are
      potentially associated with susceptibility to allergic rhinitis.

PMID- 19760212
TI  - Noise-induced hearing loss evolution: influence of age and exposure to noise.
AB  - The aims of this study were to evaluate the influence of age and exposure to
      noise in determining the evolution of hearing loss after noise-induced hearing
      loss has been already established and to define the further evolution of
      presbycusis. This is a cross-sectional study based on the evaluation of pure-tone
      audiometry threshold on 568 subjects affected by noise-induced hearing loss and
      exposed to noise for at least 10 years; noise exposure at testing was 85-90 dB
      Leqd(A). The further evolution of hearing loss was found to be more related to
      age than to noise exposure and was significantly less than expected for
      presbycusis. In conclusion our data support the hypothesis that once NIHL has
      manifested, it tends to worsen slightly with continued noise exposure and that
      progressive hearing loss is chiefly due to aging. However, in individuals with
      NIHL, age-related hearing loss is significantly less at frequencies damaged by
      noise than in non-noise-exposed individuals.

PMID- 19760213
TI  - Destructive tumours of the larynx mimicking osteosarcoma: two cases of
      osteoblastoma with organ-saving resection and follow-up.
AB  - Osteoblastoma of the larynx is an extremely rare type of locally progressive and
      destructive tumour which is mimicking osteosarcoma radiologically and
      histologically. Since prognostic and therapeutic strategies for benign
      osteoblastoma differ from the more common osteosarcoma of the larynx, a
      meticulous pre-operative histological diagnosis is required to avoid over
      therapy. We report about two patients with osteoblastoma of the larynx with organ
      saving resection and long-period follow-up without tumour recurrence. A review of
      the literature detected five further osteoblastomas of the larynx, all in elderly
      men, like our observations. This situation is quite different from the usual
      osteoblastomas of bone, which occur in young adults of both sexes equally.

PMID- 19760214
TI  - Social withdrawal after laryngectomy.
AB  - This investigation focuses on the psychosocial concomitants of a laryngectomy.
      Semistructured interviews were conducted with 218 laryngectomized patients.
      Standardised questionnaires were used to assess patients' social activity (FPAL,
      EORTC QLQ-C30), intelligibility of speech (PLTT, FPAL), mental well-being (HADS),
      and perceived stigmatisation (FPAL). More than 40% of the patients withdrew from
      conversation. Only one-third of all patients regularly took part in social
      activities. About 87% perceived stigmatisation because of their changed voice and
      more than 50% felt embarrassed because of their tracheostoma. Almost one-third of
      the patients had increased anxiety and depression scores. Moderate objective
      speech intelligibility was found, though patients were not particularly satisfied
      with their voice. Social activity emerged to be independent from age, gender,
      treatment variables, and stage of disease. Multivariate analysis resulted in two
      independent factors representing two patterns of social withdrawal. On the one
      hand, there was withdrawal from conversation accompanied by increased depression
      and poor speech intelligibility. On the other hand, there were reduced social
      activities accompanied by increased anxiety and perceived stigmatisation.

PMID- 19760215
TI  - Genetic diversity and population structure analysis of accessions in the US
      historic sweet sorghum collection.
AB  - Sweet sorghum has the potential to become a versatile feedstock for large-scale
      bioenergy production given its sugar from stem juice, cellulose/hemicellulose
      from stalks, and starch from grain. However, for researchers to maximize its
      feedstock potential a first step includes additional evaluations of the 2,180
      accessions with varied origins in the US historic sweet sorghum collection. To
      assess genetic diversity of this collection for bioenergy breeding and population
      structure for association mapping, we selected 96 accessions and genotyped them
      with 95 simple sequence repeat markers. Subsequent genetic diversity and
      population structure analysis methods identified four subpopulations in this
      panel, which correlated well with the geographic locations where these accessions
      originated or were collected. Model comparisons for three quantitative traits
      revealed different levels of population structure effects on flowering time,
      plant height, and brix. Our results suggest that diverse germplasm accessions
      curated from different geographical regions should be considered for plant
      breeding programs to develop sweet sorghum cultivars or hybrids, and that this
      sweet sorghum panel can be further explored for association mapping.

PMID- 19760216
TI  - Mapping of QTLs for lateral and axile root growth of tropical maize.
AB  - Maize genotypes may adapt to dry environments by avoiding desiccation by means of
      a deeper root system or by maintaining growth and water extraction at low water
      potentials. The aim of this study was to determine the quantitative genetic
      control of root growth and root morphology in a population of 236 recombinant
      inbred lines (RILs) from the cross between CML444 (high-yielding) x SC-Malawi
      (low-yielding), which segregates for the response to drought stress at flowering.
      The RILs and the parental lines were grown on blotting paper in growth pouches
      until the two-leaf stage under non-stressed conditions; the parents were
      additionally exposed to desiccation stress induced by polyethylene glycol with a
      molecular weight of 8000 Dalton (PEG-8000). The lengths of axile and lateral
      roots were measured non-destructively at 2, 5, 7 and 9 days after germination, by
      scanning with an A4 scanner followed by digital image analysis. CML444 had a
      lower rate constant of lateral root elongation (k(Lat)) than SC-Malawi, but the
      two genotypes did not differ in their response to desiccation. QTLs affecting
      root vigor, as depicted by increments in k(Lat), the elongation rate of axile
      roots (ER(Ax)) and the number of axile roots (No(Ax)) were identified in bins
      2.04 and 2.05. QTLs for No(Ax) and ER(Ax) collocated with QTLs for yield
      parameters in bins 1.03-1.04 and 7.03-04. The correspondence of QTLs for axile
      root traits in bins 1.02-1.03 and 1.08 and QTLs for lateral roots traits in bins
      2.04-2.07 in several mapping populations suggests the presence of genes
      controlling root growth in a wide range of genetic backgrounds.

PMID- 19760217
TI  - Meta-analysis of incidence and risk of hypokalemia with cetuximab-based therapy
      for advanced cancer.
AB  - PURPOSE: To gain a better understanding of the incidence and risk of hypokalemia
      in patients who received cetuximab-based therapy. PATIENTS AND METHODS:
      Databases, including Pubmed, EMBASE, The Cochrane Library, annual meeting of
      American Society of Clinical Oncology (2000-2008), and Web of science were
      searched to identify relevant studies. Eligible studies were prospective phase II
      III clinical trials of patients with cancer assigned cetuximab at the dose of 400
      mg/m(2) IV on day 1 and 250 mg/m(2) weekly thereafter. The primary endpoint was
      incidence of hypokalemia. RESULTS: Eleven clinical reports were identified which
      included a total of 2,254 patients who were available for analysis, with 1,324
      patients assigned cetuximab-based treatment. The results showed high incidence of
      grade 3 and 4 hypokalemia [6.2% (95% CI 4.9-7.7)] and high incidence of all-grade
      hypokalemia [8.0% (95% CI 4.5-13.9)] associated with cetuximab-based therapy for
      advanced cancer. Compared with non-cetuximab therapy, cetuximab-based therapy has
      higher risk of grade 3 and 4 hypokalemia [1.81 (95% CI 1.12-2.93)]. CONCLUSION:
      Cetuximab-based therapy is associated with a significant risk of hypokalemia.
      Early monitoring and effective management of hypokalemia is important for
      patients that received cetuximab-based therapy.

PMID- 19760218
TI  - Zoledronic acid in the treatment of bone metastases by hepatocellular carcinoma:
      a case series.
AB  - PURPOSE: The survival of patients with hepatocellular carcinoma (HCC) has
      improved with advancements in various diagnostic tools and treatment modalities.
      Consequently, bone metastases from HCC are diagnosed more frequently. The aims of
      the present study was to describe the clinical features and treatment of HCC
      patients presenting with bone metastases. In particular, we evaluated the role of
      zoledronic acid in these patients especially with regard to pain reduction,
      analgesic drug consumption and safety. METHODS: Between December 2006 and July
      2008, we recruited 17 (male:female, 12:5, median age, 68 years; age range, 62-85
      years) consecutive patients. Spinal metastases were present in 11 patients
      (64.7%). Zoledronic acid was administered in all patients (total number of
      administrations, 107; mean number of administrations, 6.29). RESULTS: A total of
      15 patients received at least three administrations of zoledronic acid and
      reported clinical benefit with pain reduction and tapering of analgesic drugs.
      Before starting treatment, the mean VAS for patients who received at least three
      administrations (15/17 patients) of zoledronic acid was 7.1 (+/-0.24), and after
      3 months 5.3 (+/-0.20). This improvement was independent of the sex, the extent
      of metastasis and the concomitant anticancer treatment. No significant side
      effects were registered in this series of patients. Median survival was 10 months
      (CI 6,353-13,647). CONCLUSIONS: Zoledronic acid may be helpful in treating bone
      metastases in HCC patients. Patients regularly receiving zoledronic acid showed
      significant pain relief.

PMID- 19760219
TI  - Impact of Cytomegalovirus infection on immune signatures in cancer patients.

PMID- 19760220
TI  - Evaluation of liposomal clodronate for treatment of malignant histiocytosis in
      dogs.
AB  - Malignant histiocytosis (MH) is an aggressive cancer derived from myeloid lineage
      cells in both dogs and humans. In dogs, the tumor is characterized by the rapid
      development of metastatic tumors in multiple sites, including especially the
      lungs and lymph nodes. Humans develop an analogous disease known as Langerhans
      cell histiocytosis, which primarily affects children and young adults. Because
      these tumors are often resistant to conventional chemotherapy, there is a need
      for newer therapeutic approaches. Systemic administration of liposomal clodronate
      (LC) has been shown to effectively deplete phagocytic cells (e.g., macrophages
      and dendritic cells) in mice. We investigated therefore whether LC could also be
      used to treat naturally occurring MH in dogs. First, the susceptibility of canine
      MH cells to LC-mediated killing was assessed in vitro. Then the clinical safety
      and effectiveness of LC as a treatment for MH was assessed in a pilot study in
      five pet dogs with spontaneous MH. We found that canine MH cells were very
      susceptible to LC-induced apoptotic cell death, whereas other tumor cell lines
      were resistant to killing by LC. Studies using labeled liposomes demonstrated
      that susceptibility to LC killing was directly related to the efficiency of
      liposome uptake. In pet dogs with spontaneous MH, we found that a short course of
      LC treatment elicited significant tumor regression in two of five treated
      animals. These findings suggest that liposomal delivery of clodronate and
      possibly other bisphosphonates may offer an effective new approach to treatment
      of histiocytic neoplasms in dogs and humans.

PMID- 19760221
TI  - Prognostic value of CD208-positive cell infiltration in gastric cancer.
AB  - BACKGROUND AND AIM: A new marker, CD208, was recently explored as a mature
      interdigitating dendritic cell (DC), and the correlation between the infiltration
      of CD208-positive cells and clinical factors has been reported in various types
      of cancers. In this study, we tried to clarify the clinical implication of CD208
      positive cell infiltration in gastric cancer immunohistochemically. PATIENTS AND
      METHODS: A total of 128 gastric cancer patients who underwent a curative
      operation were enrolled. DCs in tumor nests were identified with two DC markers,
      CD208 and S-100 protein (S100), by immunohistochemistry. The correlation between
      clinicopathological features and the CD208- or S100-positive cell infiltration
      degree was analyzed. RESULTS: Infiltration of S100-positive cells did not
      correlate with the degree of CD208-positive cell infiltration. Patients with high
      CD208-positive cell infiltration in the peritumor had a poorer surgical outcome
      than those with low CD208 infiltration (p < 0.05). Multivariate analysis revealed
      that CD208-positive cell infiltration was not an independent prognostic factor.
      CONCLUSION: We showed that intratumoral CD208-positive cells, as mature DCs, had
      an inverse correlation to patients' postoperative outcome in gastric cancer,
      unlike a conventional DC marker. Evaluation of CD208-positive cell infiltration
      with S100-positive cell infiltration in gastric cancer is useful to predict
      antitumor immunological conditions in gastric cancer.

PMID- 19760222
TI  - Anatomical description of the periprostatic nerves in the male rhesus monkey
      (Macaca mulatta).
AB  - OBJECTIVES: Recent publications have revealed a variable course of the
      periprostatic nerves in humans. It is unclear to what extent nerves outside the
      dorsolateral region of the prostate are involved in the physiology of erectile
      function. As functional studies in humans are limited by ethical aspects
      investigations in animal models could provide further insight. The intention of
      this study was to give a detailed description of the topographical anatomy of
      autonomic nerves along the seminal vesicles and the prostate in male rhesus
      monkeys (Macaca mulatta) to investigate its suitability as an animal model for
      future physiological studies. METHODS: Wholemount serial sections of pelvic organ
      blocks of ten male rhesus monkeys were investigated. Autonomic nerves were
      stained with an antibody against S100. RESULTS: Autonomic nerves were dispersed
      along the dorsolateral to the ventrolateral aspect of the capsule of the prostate
      within a layer of connective tissue. There was no accumulation of vessels and
      nerves in the dorsolateral position of the prostate. The prostate is located
      dorsally to the urethra and does not encircle it. No adjacent nerves were found
      in the cranial two-thirds of the seminal vesicles. CONCLUSIONS: The male rhesus
      monkey is limited suitable as an animal model for studies on the periprostatic
      nerves provided the following differences to humans are considered: the special
      topography of the prostate, the nerve course along the seminal vesicles and the
      missing nerve accumulation dorsolaterally to the prostate.

PMID- 19760223
TI  - Relationship between angiographic and optical coherence tomographic (OCT)
      parameters for quantifying choroidal neovascular lesions.
AB  - BACKGROUND: To correlate the volume of various spaces on optical coherence
      tomography (OCT) with fluorescein angiographic (FA) parameters in neovascular age
      related macular degeneration (AMD). METHODS: Sixty-five consecutive cases of
      active subfoveal choroidal neovascularization (CNV) associated with AMD were
      retrospectively collected. Area and greatest linear dimension of CNV lesion
      components were calculated on FA. Corresponding StratusOCT image sets were
      analyzed using custom software (termed OCTOR), which allows manual measurement of
      the volume of the neurosensory retina, subretinal fluid, subretinal tissue, and
      pigment epithelial detachment (PED). RESULTS: Area of occult CNV on FA correlated
      with PED (R = 0.62) and subretinal fluid (R = 0.28) volume and negatively with
      subretinal tissue volume (R = -0.26) on OCT. Area of classic CNV on FA correlated
      with subretinal tissue (R = 0.60) and retinal (R = 0.38) volume on OCT. Automated
      StratusOCT output values showed poorer correlations than manually calculated
      OCTOR values. CONCLUSIONS: OCT features of CNV lesions as measured by manual
      quantitative subanalysis correlate better with angiographic parameters than
      values provided by the automated StratusOCT analysis. These measures may improve
      our understanding of the morphologic effects of CNV lesions and may facilitate
      the development of a hybrid FA and OCT-based classification system for future
      clinical trials, which more fully characterizes CNV lesions.

PMID- 19760224
TI  - Reproducibility of color Doppler imaging.
AB  - PURPOSE: The aims of this study were: (1) to determine the intra-subject and
      inter-observer variability of color Doppler imaging (CDI) measurements and
      readings of the retrobulbar blood vessels, (2) to compare the difference
      invariability of CDI parameters in non-glaucomatous controls versus glaucoma
      patients, and (3) to provide calculations of minimum sample sizes for future CDI
      studies. METHODS: Patients with normal tension glaucoma (n=28), primary open
      angle glaucoma (n=19) and non-glaucomatous controls of comparable age (n=22)
      underwent CDI on two occasions 1 month apart. Variability in CDI parameters was
      quantified using (within-subject) coefficients of variation. Based on this
      variability, minimum sample sizes were calculated to guide the design of future
      studies comparing CDI between and within groups. RESULTS: In general, within
      subject coefficients of variation for measurements 1 month apart were comparable
      to previously reported short-term variations. Variability was higher in glaucoma
      patients than in non-glaucomatous controls. The minimum sample size required for
      glaucomatous study populations is larger than for non-glaucomatous controls.
      Smaller patient groups are required to detect change using the peak systolic
      blood flow velocities than using end diastolic velocities. Studies using a cross
      over design require smaller sample sizes than studies with a prepost or
      particularly parallel design. CONCLUSIONS: This study provides extensive
      information on long-term intra-subject variability of CDI measurements in non
      glaucomatous controls as well as glaucoma patients. Moreover, sample size
      calculations are provided for studies involving glaucoma patients as well as non
      glaucomatous individuals, using three different commonly used study designs.

PMID- 19760225
TI  - Seventeen-year survival of the cementless CLS Spotorno stem.
AB  - INTRODUCTION: For primary uncemented hip arthroplasty, various stem designs are
      available. The cementless CLS((R)) Spotorno stem has been used for more than 20
      years. We re-evaluated a group of patients previously examined for a 10-year
      follow-up to assess the clinical and radiological stem performance in the long
      run. MATERIALS AND METHODS: Between 1987 and 1988, a consecutive series of 107
      uncemented CLS((R))-Spotorno stems (Zimmer Ltd., Germany) were implanted in 94
      patients. The patients' mean age at the time of surgery was 51 years (range 20-77
      years); 80 hips out of 107 (86%) were available for a clinical examination
      [Harris Hip Score (HHS)] after a mean of 17 years (range 15-18 years). In
      addition, radiographs were available from 74 out of 80 examined hips (92%) and
      analyzed for radiolucency, stress shielding, stem migration and heterotopic
      ossification. RESULTS: Stable stem fixation was present in 64 hips (98.5%). With
      "non-traumatic loosening" as an endpoint, stem survival was 100% after 17 years.
      Two stems (3%) showed mild subsidence already in the 10-year follow-up with no
      progression after 17 years. The HHS described excellent results in 47 hips (59%),
      good results in 16 hips (20%) and fair or poor results in 7 hips (9%) and 10 hips
      (13%), respectively. Radiolucency and grades II and III stress shielding were
      progressive at 17 years compared with the 10-year results. Grade IV stress
      shielding associated with osteolysis was seen in 9 hips (14%). Thigh pain was
      present in 20 hips (25%). CONCLUSION: The CLS((R)) Spotorno stem allows excellent
      long-term results in cementless hip arthroplasty, leaving only minimal options
      for substantial improvements. Our findings on progressive stress shielding point
      towards a more diaphyseal load transfer of the CLS stem.

PMID- 19760226
TI  - IIlizarov external fixator for bilateral severe flexion deformity of the knee in
      haemophilia: case report.
AB  - INTRODUCTION: Deformity correction by Illizarov method in haemophilic patients is
      a rare phenomenon. AIM: To correct the bilateral knee deformity by Illizarov in
      one sitting. MATERIALS AND METHODS: Patient had fixed flexion deformity (100
      degrees ) of both knees; posterior skin webs, posterior subluxation, wasting of
      quadriceps and <1% level of factor IX. Patient was managed with optimisation of
      factor IX level in perioperative period by factor IX supplementations.
      Deformities were corrected by Illizarov's fixator on both lower limbs at 3 months
      and fixator was removed at 4 months. At 3 months, patient developed bilateral
      equinus deformity which was corrected by a dynamic foot sling and gentle
      tendoachillis stretching exercises. RESULT: Patient had superficial pin tract
      infection at three sites. There were no episodes of bleeding from pin tracts or
      in knee joint during distraction period. Patient had bilateral knees flexion up
      to 120 degrees with 5 degrees extensor lag on the right side. Patient is going to
      college and walks with intermittent use of a hinge knee brace at 3 years follow
      up. CONCLUSION: Illizarov method is a safe, less invasive, effective, economical
      and truly biological method for correction of severe flexion deformities of knee
      in haemophilic patients.

PMID- 19760227
TI  - Nodal distances for rooted phylogenetic trees.
AB  - Dissimilarity measures for (possibly weighted) phylogenetic trees based on the
      comparison of their vectors of path lengths between pairs of taxa, have been
      present in the systematics literature since the early seventies. For rooted
      phylogenetic trees, however, these vectors can only separate non-weighted binary
      trees, and therefore these dissimilarity measures are metrics only on this class
      of rooted phylogenetic trees. In this paper we overcome this problem, by
      splitting in a suitable way each path length between two taxa into two lengths.
      We prove that the resulting splitted path lengths matrices single out arbitrary
      rooted phylogenetic trees with nested taxa and arcs weighted in the set of
      positive real numbers. This allows the definition of metrics on this general
      class of rooted phylogenetic trees by comparing these matrices through metrics in
      spaces M(n)(R) of real-valued n x n matrices. We conclude this paper by
      establishing some basic facts about the metrics for non-weighted phylogenetic
      trees defined in this way using L(p) metrics on M(n)(R), with p [epsilon] R(>0).

PMID- 19760228
TI  - Biofilm growth of individual and dual strains of Klebsiella oxytoca from the
      dairy industry on ultrafiltration membranes.
AB  - Formation of biofilms in dairy membrane plants causes membrane pore blocking,
      product contamination and subsequent economic loss. To investigate the biofilm
      growth, two Klebsiella oxytoca strains, K. B006 and TR002, previously isolated
      from New Zealand dairy membrane plants, were grown both individually and combined
      on three types of ultrafiltration (UF) membranes in different concentrations of
      whey medium in biofilm reactors (CBR 90, BioSurface Technologies, Bozeman, USA).
      Biofilms of both the individual and combined strains grew on the membrane
      surfaces to levels of 4.9-7.99 log colony-forming units (CFU) cm(-2) measured by
      standard plate counting after removing the cells by sonication. More biofilm grew
      on used polyethersulfone (PES) membranes than on new PES and polyvinylidene
      fluoride (PVDF) membranes. Both strains formed good biofilms, although K. B006
      formed a denser biofilm than TR002. This corresponded to our previous study on
      the attachment of these organisms, where K. B006 attached in greater numbers than
      K. TR002. The dual strains produced a higher biofilm density than single strains
      on the new membranes. Biofilm density tended to increase with increased whey
      concentration. The saturated biofilm was approximately 10(8) CFU cm(-2). PES
      membranes appeared to support biofilm growth less readily than did PVDF membranes
      and therefore may be the preferred material for UF membranes to reduce problems
      with microbial colonisation. Used membranes were more readily colonised with
      biofilm than were new membranes. Therefore, selecting a membrane type and
      monitoring membrane age will help manage biofilm development during UF.

PMID- 19760229
TI  - Diagnostic accuracy of high-pitch dual-source CT for the assessment of coronary
      stenoses: first experience.
AB  - OBJECTIVES: The objective was to prospectively investigate the diagnostic
      accuracy of high-pitch (HP) dual-source computed tomography coronary angiography
      (CTCA) compared with catheter coronary angiography (CCA) for the diagnosis of
      significant coronary stenoses. METHODS: Thirty-five patients (seven women; mean
      age 62 +/- 8 years) underwent both CTCA and CCA. CTCA was performed with a second
      generation dual-source CT system permitting data acquisition at an HP of 3.4.
      Patients with heart rates >60 bpm were excluded from study enrolment. All
      coronary segments were evaluated by two blinded and independent observers with
      regard to image quality on a four-point scale (1: excellent to 4: non-diagnostic)
      and for the presence of significant coronary stenoses (defined as diameter
      narrowing exceeding 50%). CCA served as the standard of reference. Radiation dose
      values were calculated using the dose-length product. RESULTS: Diagnostic image
      quality was found in 99% of all segments (455/459). Non-diagnostic image quality
      occurred in a single patient with a sudden increase in heart rate immediately
      before and during CTCA. Taking segments with non-evaluative image quality as
      positive for disease, the sensitivity, specificity and positive and negative
      predictive values were 94, 96, 80 and 99% per segment and 100, 91, 88 and 100%
      per patient. The effective radiation dose was on average 0.9 +/- 0.1 mSv.
      CONCLUSION: In patients with heart rates <=60 bpm, CTCA using the HP mode of the
      dual-source CT system is associated with high diagnostic accuracy for the
      assessment of coronary artery stenoses at sub-milli-Sievert doses.

PMID- 19760230
TI  - Coronary calcium score and computed tomography coronary angiography in high-risk
      asymptomatic subjects: assessment of diagnostic accuracy and prevalence of non
      obstructive coronary artery disease.
AB  - OBJECTIVES: The aim of the study was to compare the coronary artery calcium score
      (CACS) and computed tomography coronary angiography (CTCA) for the assessment of
      non-obstructive/obstructive coronary artery disease (CAD) in high-risk
      asymptomatic subjects. METHODS: Two hundred and thirteen consecutive asymptomatic
      subjects (113 male; mean age 53.6 +/- 12.4 years) with more than one risk factor
      and an inconclusive or unfeasible non-invasive stress test result underwent CACS
      and CTCA in an outpatient setting. All patients underwent conventional coronary
      angiography (CAG). Data from CACS (threshold for positive image: Agatston score
      1/100/1,000) and CTCA were compared with CAG regarding the degree of CAD (non
      obstructive/obstructive; </>or=50% lumen reduction). RESULTS: The mean calcium
      score was 151 +/- 403 and the prevalence of obstructive CAD was 17% (8% one
      vessel and 10% two-vessel disease). Per-patient sensitivity, specificity,
      positive and negative predictive values of CACS were: 97%, 75%, 45%, and 100%,
      respectively (Agatston >or=1); 73%, 90%, 60%, and 94%, respectively (Agatston
      >or=100); 30%, 98%, 79%, and 87%, respectively (Agatston >or=1,000). Per-patient
      values for CTCA were 100%, 98%, 97%, and 100%, respectively (p < 0.05). CTCA
      detected 65% prevalence of all CAD (48% non-obstructive), while CACS detected 37%
      prevalence of all CAD (21% non-obstructive) (p < 0.05). CONCLUSION: CACS proved
      inadequate for the detection of obstructive and non-obstructive CAD compared with
      CTCA. CTCA has a high diagnostic accuracy for the detection of non-obstructive
      and obstructive CAD in high-risk asymptomatic patients with inconclusive or
      unfeasible stress test results.

PMID- 19760231
TI  - Radiofrequency ablation of small liver malignancies under magnetic resonance
      guidance: progress in targeting and preliminary observations with temperature
      monitoring.
AB  - OBJECTIVES: To evaluate the feasibility and effectiveness of magnetic resonance
      (MR)-guided radiofrequency (RF) ablation for small liver tumours with poor
      conspicuity on both contrast-enhanced ultrasonography (US) and computed
      tomography (CT), using fast navigation and temperature monitoring. METHODS:
      Sixteen malignant liver nodules (long-axis diameter, 0.6-2.4 cm) were treated
      with multipolar RF ablation on a 1.5-T wide-bore MR system in ten patients.
      Targeting was performed interactively, using a fast steady-state free precession
      sequence. Real-time MR-based temperature mapping was performed, using gradient
      echo-echo planar imaging (GRE-EPI) and hardware filtering. MR-specific treatment
      data were recorded. The mean follow-up time was 19 +/- 7 months. RESULTS: Correct
      placement of RF electrodes was obtained in all procedures (image update, <500 ms;
      mean targeting time, 21 +/- 11 min). MR thermometry was available for 14 of 16
      nodules (88%) with an accuracy of 1.6 degrees C in a non-heated region. No
      correlation was found between the size of the lethal thermal dose and the
      ablation zone at follow-up imaging. The primary and secondary effectiveness rates
      were 100% and 91%, respectively. CONCLUSIONS: RF ablation of small liver tumours
      can be planned, targeted, monitored and controlled with MR imaging within
      acceptable procedure times. Temperature mapping is technically feasible, but the
      clinical benefit remains to be proven.

PMID- 19760232
TI  - Radiofrequency ablation of hepatic tumours: effect of post-ablation margin on
      local tumour progression.
AB  - PURPOSE: The purpose of this study was to retrospectively evaluate the
      relationship between post-ablation margins and local tumour progression following
      radiofrequency ablation (RFA) of hepatocellular carcinomas and colorectal liver
      metastases. METHODS: Eighty-three patients with 107 hepatic tumours who underwent
      RFA were divided into two groups: the hepatocellular carcinoma (HCC) group (55
      patients with 69 lesions) and the colorectal liver metastases group (28 patients
      with 38 lesions). Post-ablation margins were calculated on 1-month follow-up
      contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI)
      studies. Efficacy was evaluated at 1-month post-ablation, then at 3-month
      intervals for the first year and biannually thereafter. RESULTS: The results of
      the log-rank test showed that the minimum threshold post-ablation margin of 0.4
      cm (P = 0.020) and tumour size smaller than 2.5 cm (P = 0.001) significantly
      correlated with local control for the HCC group. In the colorectal liver
      metastases group, the results of the log-rank test showed that the minimum
      threshold post-ablation margin of 0.4 cm (P = 0.345) and tumour size smaller than
      2.5 cm (P = 0.168) did not correlate with local control. CONCLUSION: Percutaneous
      RFA is more effective in achieving local control in patients with HCCs than with
      colorectal liver metastases.

PMID- 19760233
TI  - Criteria for the selective use of chest computed tomography in blunt trauma
      patients.
AB  - PURPOSE: The purpose of this study was to derive parameters that predict which
      high-energy blunt trauma patients should undergo computed tomography (CT) for
      detection of chest injury. METHODS: This observational study prospectively
      included consecutive patients (>or=16 years old) who underwent multidetector CT
      of the chest after a high-energy mechanism of blunt trauma in one trauma centre.
      RESULTS: We included 1,047 patients (median age, 37; 70% male), of whom 508 had
      chest injuries identified by CT. Using logistic regression, we identified nine
      predictors of chest injury presence on CT (age >or=55 years, abnormal chest
      physical examination, altered sensorium, abnormal thoracic spine physical
      examination, abnormal chest conventional radiography (CR), abnormal thoracic
      spine CR, abnormal pelvic CR or abdominal ultrasound, base excess <-3 mmol/l and
      haemoglobin <6 mmol/l). Of 855 patients with >or=1 positive predictors, 484 had
      injury on CT (95% of all 508 patients with injury). Of all 192 patients with no
      positive predictor, 24 (13%) had chest injury, of whom 4 (2%) had injuries that
      were considered clinically relevant. CONCLUSION: Omission of CT in patients
      without any positive predictor could reduce imaging frequency by 18%, while most
      clinically relevant chest injuries remain adequately detected.

PMID- 19760234
TI  - Towards risk stratification in systemic atherosclerosis: value of myocardial
      function and viability imaging as an adjunct to MR angiography.
AB  - OBJECTIVES: To longitudinally assess the value of cardiac functional and
      viability imaging as a supplement to MR angiography in patients with
      atherosclerotic disease. METHODS: Cardiac MRI was performed in 195 consecutive
      patients with symptomatic peripheral arterial disease. Of these, 186 patients
      were followed for 22 +/- 5 months for the presence of cardiac events (cardiac
      death, acute coronary syndrome and hospitalisation as a result of congestive
      heart failure). RESULTS: Myocardial viability imaging showed a high prevalence of
      known (n = 31) and occult myocardial infarctions (MI) (n = 26). Cardiac events
      occurred more often in patients with reduced ventricular function (ejection
      fraction (EF) less than 40%, cardiac event in 4/8 patients; EF 40-55%, cardiac
      event in 10/40 patients; EF greater than 55%, cardiac event in 15/138 patients)
      as well as in patients with occult MI (8/25 patients) and known MI (11/30
      patients). In patients with normal function, the detection of a previous MI was
      of high relevance to prognosis. CONCLUSIONS: Both reduced EF and the presence of
      MI influence patients' prognoses. Performing cardiac MRI in this patient
      population may influence further patient management including intensified risk
      factor intervention.

PMID- 19760235
TI  - Three-dimensional textural analysis of brain images reveals distributed grey
      matter abnormalities in schizophrenia.
AB  - OBJECTIVES: Three-dimensional (3-D) selective- and relative-scale texture
      analysis (TA) was applied to structural magnetic resonance (MR) brain images to
      quantify the presence of grey-matter (GM) and white-matter (WM) textural
      abnormalities associated with schizophrenia. MATERIALS AND METHODS: Brain TA
      comprised volume filtration using the Laplacian of Gaussian filter to highlight
      fine, medium and coarse textures within GM and WM, followed by texture
      quantification. Relative TA (e.g. ratio of fine to medium) was also computed. T1
      weighted MR whole-brain images from 32 participants with diagnosis of
      schizophrenia (n = 10) and healthy controls (n = 22) were examined. Five patients
      possessed marker alleles (SZ8) associated with schizophrenia on chromosome 8 in
      the pericentriolar material 1 gene while the remaining five had not inherited any
      of the alleles (SZ0). RESULTS: Filtered fine GM texture (mean grey-level
      intensity; MGI) most significantly differentiated schizophrenic patients from
      controls (P = 0.0058; area under the receiver-operating characteristic curve =
      0.809, sensitivity = 90%, specificity = 70%). WM measurements did not distinguish
      the two groups. Filtered GM and WM textures (MGI) correlated with total GM and WM
      volume respectively. Medium-to-coarse GM entropy distinguished SZ0 from controls
      (P = 0.0069) while measures from SZ8 were intermediate between the two.
      CONCLUSIONS: 3-D TA of brain MR enables detection of subtle distributed
      morphological features associated with schizophrenia, determined partly by
      susceptibility genes.

PMID- 19760236
TI  - Evaluation of image quality and lesion perception by human readers on 3D CT
      colonography: comparison of standard and low radiation dose.
AB  - AIMS: We compared the prevalence of noise-related artefacts and lesion perception
      on three-dimensional (3D) CT colonography (CTC) at standard and low radiation
      doses. METHODS: Forty-eight patients underwent CTC (64 x 0.625 mm collimation;
      tube rotation time 0.5 s; automatic tube current modulation: standard dose 40-160
      mA, low dose 10-50 mA). Low- and standard-dose acquisitions were performed in the
      supine position, one after the other. The presence of artefacts (cobblestone and
      snow artefacts, irregularly delineated folds) and the presence of polyps were
      evaluated by five radiologists on 3D images at standard dose, the original low
      dose and a modified low dose, i.e. after manipulation of opacity on 3D. RESULTS:
      The mean effective dose was 3.9 +/- 1.3 mSv at standard dose and 1.03 +/- 0.4 mSv
      at low dose. The number of images showing cobblestone artefacts and irregularly
      delineated folds at original and modified low doses was significantly higher than
      at standard dose (P < 0.0001). Most of the artefacts on modified low-dose images
      were mild. No significant difference in sensitivity between the dose levels was
      found for polyps > or =6 mm. CONCLUSIONS: Reduction of the effective dose to 1
      mSv significantly affects image quality on 3D CTC, but the perception of > or =6
      mm lesions is not significantly impaired.

PMID- 19760237
TI  - Computer-aided detection (CAD) of lung nodules in CT scans: radiologist
      performance and reading time with incremental CAD assistance.
AB  - OBJECTIVE: The diagnostic performance of radiologists using incremental CAD
      assistance for lung nodule detection on CT and their temporal variation in
      performance during CAD evaluation was assessed. METHODS: CAD was applied to 20
      chest multidetector-row computed tomography (MDCT) scans containing 190 non
      calcified > or =3-mm nodules. After free search, three radiologists independently
      evaluated a maximum of up to 50 CAD detections/patient. Multiple free-response
      ROC curves were generated for free search and successive CAD evaluation, by
      incrementally adding CAD detections one at a time to the radiologists'
      performance. RESULTS: The sensitivity for free search was 53% (range, 44%-59%) at
      1.15 false positives (FP)/patient and increased with CAD to 69% (range, 59-82%)
      at 1.45 FP/patient. CAD evaluation initially resulted in a sharp rise in
      sensitivity of 14% with a minimal increase in FP over a time period of 100 s,
      followed by flattening of the sensitivity increase to only 2%. This transition
      resulted from a greater prevalence of true positive (TP) versus FP detections at
      early CAD evaluation and not by a temporal change in readers' performance. The
      time spent for TP (9.5 s +/- 4.5 s) and false negative (FN) (8.4 s +/- 6.7 s)
      detections was similar; FP decisions took two- to three-times longer (14.4 s +/-
      8.7 s) than true negative (TN) decisions (4.7 s +/- 1.3 s). CONCLUSIONS: When CAD
      output is ordered by CAD score, an initial period of rapid performance
      improvement slows significantly over time because of non-uniformity in the
      distribution of TP CAD output and not to a changing reader performance over time.

PMID- 19760238
TI  - Real-time fMRI feedback training may improve chronic tinnitus.
AB  - OBJECTIVES: Tinnitus consists of a more or less constant aversive tone or noise
      and is associated with excess auditory activation. Transient distortion of this
      activation (repetitive transcranial magnetic stimulation, rTMS) may improve
      tinnitus. Recently proposed operant training in real-time functional magnetic
      resonance imaging (rtfMRI) neurofeedback allows voluntary modification of
      specific circumscribed neuronal activations. Combining these observations, we
      investigated whether patients suffering from tinnitus can (1) learn to
      voluntarily reduce activation of the auditory system by rtfMRI neurofeedback and
      whether (2) successful learning improves tinnitus symptoms. METHODS: Six
      participants with chronic tinnitus were included. First, location of the
      individual auditory cortex was determined in a standard fMRI auditory block
      design localizer. Then, participants were trained to voluntarily reduce the
      auditory activation (rtfMRI) with visual biofeedback of the current auditory
      activation. RESULTS: Auditory activation significantly decreased after rtfMRI
      neurofeedback. This reduced the subjective tinnitus in two of six participants.
      CONCLUSION: These preliminary results suggest that tinnitus patients learn to
      voluntarily reduce spatially specific auditory activations by rtfMRI
      neurofeedback and that this may reduce tinnitus symptoms. Optimized training
      protocols (frequency, duration, etc.) may further improve the results.

PMID- 19760239
TI  - Retrospective analysis of patients for development of nephrogenic systemic
      fibrosis following conventional angiography using gadolinium-based contrast
      agents.
AB  - PURPOSE: The purpose was to retrospectively review the data of 27 patients with
      renal insufficiency who underwent conventional angiography with gadolinium-based
      contrast agents (GDBCA) as alternative contrast agents and assess the occurrence
      of nephrogenic systemic fibrosis (NSF) together with associated potential risk
      factors. METHODS: This HIPAA-compliant study had institutional review board
      approval, and informed consent was waived. Statistical analysis was performed for
      all available laboratory and clinical data, including dermatology reports. Type
      and amount of the GDBCA used were recorded for angiography and additional MRI
      studies, if applicable. Serum creatinine levels (SCr) pre- and post-angiography
      were recorded, and estimated glomerular filtration rates (eGFR) were calculated.
      RESULTS: Ten female and 17 male patients who underwent angiography with GDBCA
      were included. The mean amount of GDBCA administered was 44 +/- 15.5 ml (range 15
      60 ml) or 0.24 + 0.12 mmol/kg (range 0.1-0.53 mmol/kg). At the time of
      angiography all patients had renal insufficiency (eGFR <60 ml/min/1.73 m(2)).
      Mean eGFR pre-angiography was 26 ml/min/1.73 m(2) and 33 ml/min/1.73 m(2) post
      angiography. The mean follow-up period covers 28 months, range 1-84 months.
      Additional MRI studies with GDBCA administration were performed in 15 patients.
      One patient with typical skin lesions had developed biopsy-confirmed NSF.
      CONCLUSION: Conventional arterial angiography with GDBCA may play a role in the
      development of NSF in patients with renal insufficiency. Alternative contrast
      agents, such as CO(2) angiography or rather the use of low doses of iodinated
      contrast agents, should be considered in these patients.

PMID- 19760240
TI  - Volume changes in Alzheimer's disease and mild cognitive impairment: cognitive
      associations.
AB  - OBJECTIVE: To assess the relationship between MRI-derived changes in whole-brain
      and ventricular volume with change in cognitive scores in Alzheimer's disease
      (AD), mild cognitive impairment (MCI) and control subjects. MATERIAL AND METHODS:
      In total 131 control, 231 MCI and 99 AD subjects from the Alzheimer's Disease
      Neuroimaging Initiative (ADNI) cohort with T1-weighted volumetric MRIs from
      baseline and 12-month follow-up were used to derive volume changes. Mini mental
      state examination (MMSE), Alzheimer's disease assessment scale (ADAS)-cog and
      trails test changes were calculated over the same period. RESULTS: Brain atrophy
      rates and ventricular enlargement differed between subject groups (p < 0.0005)
      and in MCI and AD were associated with MMSE changes. Both measures were
      additionally associated with ADAS-cog and trails-B in MCI patients, and
      ventricular expansion was associated with ADAS-cog in AD patients. Brain atrophy
      (p < 0.0005) and ventricular expansion rates (p = 0.001) were higher in MCI
      subjects who progressed to AD within 12 months of follow-up compared with MCI
      subjects who remained stable. MCI subjects who progressed to AD within 12 months
      had similar atrophy rates to AD subjects. CONCLUSION: Whole-brain atrophy rates
      and ventricular enlargement differed between patient groups and healthy controls,
      and tracked disease progression and psychological decline, demonstrating their
      relevance as biomarkers.

PMID- 19760241
TI  - High resolution myocardial magnetic resonance stress perfusion imaging at 3 T
      using a 1 M contrast agent.
AB  - OBJECTIVE: Stress perfusion magnetic resonance imaging (MSPMRI) is an established
      technique for the assessment of myocardial perfusion. Shortcomings at 1.5 T are
      low signal to noise ratio (SNR) and contrast to noise ratio (CNR). One approach
      to overcome these shortcomings is to increase field strength and contrast
      concentration. The aim of our study was to investigate the diagnostic capability
      of high resolution MSPMRI at 3-T field strength using a 1 M contrast agent.
      MATERIAL AND METHODS: Fifty-seven patients (62.3 +/- 11.0 years) with symptoms of
      coronary artery disease (CAD) were examined at 3 T. MMRSPI was assessed using a
      2D saturation recovery gradient echo (SR GRE) sequence in short axis orientation
      (TR 1.9 ms, TE 1.0 ms, flip 12 degrees , 0.1 mmol gadobutrol/kg body weight (bw),
      140 microg adenosine/kg bw/min). Perfusion images were assessed visually and
      semiquantitatively (upslope, peak signal intensity (SI), and myocardial perfusion
      reserve index (MPRI)). Standard of reference was invasive coronary angiography.
      RESULTS: Stress-induced hypoperfusion was found in 43 patients. Sensitivity for
      hemodynamically relevant CAD (stenoses greater than 70%) was 95%/98%, specificity
      80%/87%, diagnostic accuracy 91%/95% (reader 1/reader 2). The MPRI was
      significantly lower in hypoperfused myocardium (1.3 +/- 0.2) compared with normal
      myocardium (2.6 +/- 0.7). CONCLUSION: High resolution MMRSPI at 3 T using 1 M
      contrast agent under daily routine conditions provides reliable detection of
      stress-induced myocardial hypoperfusion with higher diagnostic accuracy than 1.5
      T conditions.

PMID- 19760242
TI  - Abstracts of the Fifth International Congress on MR-Mammography. September 24-26,
      2009. Jena, Germany.

PMID- 19760243
TI  - Structure-function relationships in the processing of regret in the orbitofrontal
      cortex.
AB  - The influence of counterfactual thinking and regret on choice behavior has been
      widely acknowledged in economic science (Bell in Oper Res 30:961-981, 1982;
      Kahneman and Tversky in Judgment under uncertainty: heuristics and biases.
      Cambridge University Press, Cambridge, pp 201-210, 1982; Loomes and Sugden in
      Econ J 92:805-824, 1982). Neuroimaging studies have only recently begun to
      explore the neural correlates of this psychological factor and orbitofrontal
      cortex (OFC) activity was observed in several of them depending of the exact
      characteristics of the employed paradigm. This selective OFC involvement and,
      moreover, a consistently found dissociation of medial and lateral OFC activity
      clusters allow inferences to the function of this structure in counterfactual
      thinking and regret. Vice versa, the differential contribution of OFC subregions
      to these processes also adds evidence to the current debate on the function of
      this cortical structure in decision-making that attracted increasing attention in
      recent years.

PMID- 19760244
TI  - In vitro simultaneous transfer of lipids to HDL in coronary artery disease and in
      statin treatment.
AB  - The exchange of lipids with cells and other lipoproteins is a crucial process in
      HDL metabolism and for HDL antiatherogenic function. Here, we tested a practical
      method to quantify the simultaneous transfer to HDL of phospholipids, free
      cholesterol, esterified cholesterol and triacylglycerols and to verify the lipid
      transfer in patients with coronary artery disease (CAD) or undergoing statin
      treatment. Twenty-eight control subjects without CAD, 27 with CAD and 25 CAD
      patients under simvastatin treatment were studied. Plasma samples were incubated
      with a donor nanoemulsion prepared by ultrasonication of the constituent lipids
      and labeled with radioactive lipids; % lipids transferred to HDL were quantified
      in the HDL-containing supernatant after chemical precipitation of non-HDL
      fractions and the nanoemulsion. The assay was precise and reproducible. Increase
      of temperature (4-37 degrees C), of incubation period (5 min to 2 h), of HDL
      cholesterol concentration (33-244 mg/dL) and of mass of nanoemulsion lipids
      (0.075-0.3 mg/microL) resulted in increased lipid transfer from the nanoemulsion
      to HDL. In contrast, increasing pH (6.5-8.5) and albumin concentration (3.5-7.0
      g/dL) did not affect lipid transfer. There was no difference between CAD and
      control non-CAD with regard to the lipid transfer, but statin treatment reduced
      the transfer to HDL of all four lipids. The test herein described is a valid and
      practical tool for exploring an important aspect of HDL metabolism.

PMID- 19760245
TI  - [Once again: theoretical pathology].
AB  - Theoretical pathology refers to the attempt to reintroduce methodical approaches
      from the humanities, philosophical logic and "gestalt philosophy" into medical
      research and pathology. Diseases, in particular disease entities and more complex
      polypathogenetic mechanisms of disease, have a "gestalt quality" due to the
      significance of their pathophysiologic coherence: they have a "gestalt". The
      Research group Theoretical Pathology at the Academy of Science in Heidelberg are
      credited with having revitalized the philosophical notion of "gestalt" for
      morphological and pathological diagnostics. Gestalt means interrelated schemes of
      pathophysiological significance in the mind of the diagnostician. In pathology,
      additive and associative diagnostic are simply not possible without considering
      the notion of synthetic entities in Kant's logic.

PMID- 19760246
TI  - [Novel vaccines. Vaccinations in the near and distant future].
AB  - Easy-to-develop vaccines usually induce antibodies against acute, self-limiting
      infections by stable pathogens. Today, most of these vaccines have been made, and
      the future diseases to tackle are more challenging: highly variable pathogens,
      rapidly emerging new infections with the potential of developing into pandemics,
      or therapeutic applications for chronic infections and cancer which most likely
      require complex immune responses beyond the induction of antibodies. The impact
      of scientific and technological progress on vaccinology has multiplied the
      strategies to improve vaccines. Here, we describe how genome-based approaches
      have revolutionized the way to identify vaccine antigen candidates, how the vast
      numbers of candidates can be further ranked by sophisticated gene- and protein
      array based screening methods, and how surface proteomics may accelerate this
      target identification process. Increased structural knowledge of antigens will
      allow exposing or stabilizing those antigen parts relevant for protection and
      thereby direct the immune response to them. Improved adjuvants will enhance and
      bias the immune response to induce the relevant arms of the immune system. In
      conclusion, thanks to conceptual and biotechnological progress, future vaccines
      will be safer, more efficient and more complex than those today.

PMID- 19760247
TI  - [Surveillance programmes to evaluate the effectiveness of vaccination programmes
      using vaccination against Haemophilus influenzae type b and varicella as
      examples].
AB  - To evaluate the effectiveness of vaccination programmes, it is not only important
      to know the effectiveness of the specific vaccine itself but also to have
      knowledge about the epidemiology of the corresponding vaccine-preventable
      disease. Only a high acceptance of a vaccination programme by the population will
      show an effect at the population level (herd immunity). At the moment, data
      routinely collected in Germany are not sufficient to evaluate the effectiveness
      of vaccination programmes. Hence, additional surveillance programmes have to be
      initialised. The frequency of the vaccine-preventable disease in the population
      under surveillance determines mainly the design of the surveillance. In this
      article we describe the different requirements for surveillance programmes for
      common as well as for rare vaccine-preventable diseases. An example for the
      latter will be the ESPED study on the effectiveness of hexavalent vaccines
      against Haemophilus influenzae type b, an example for the first will be the
      varicella sentinel of the Working Group on Measles and Varicella. Both
      surveillance programmes for evaluation of the effectiveness of the respective
      vaccination programme are financed only partly by the public funds. We discuss
      the possible limitations of a funding from other sources.

PMID- 19760248
TI  - [Establishment of Networks of National Reference Centres and associated
      Consiliary Laboratories in Germany].
AB  - The German Federal Ministry of Health has funded National Reference Centres (NRC)
      for laboratory-based surveillance of selected infection pathogens and infections
      disease syndromes. This selection is based on the epidemiologic relevance of the
      pathogens, specific diagnostic requirements, antimicrobial resistance and need
      for public health measures. Currently there are 18 NRC, nominated for a duration
      of 3 years. Toward the end of a nomination period, each NRC is evaluated by an
      expert committee, based on the catalogue of core tasks. In order to expand the
      spectrum of competencies 47 consiliary laboratories on additional pathogens of
      special epidemiologic importance have been named. Their main function is to
      provide information and consultation on special diagnostic issues. In order to
      further improve the effectiveness and cooperation of the system Networks have
      been created. The aim of the Networks is to facilitate exchange of diagnostic
      methods and prevention concepts and to improve the geographic coverage of the
      services.

PMID- 19760249
TI  - [Toxicological and drinking water hygienic assessment of relevant and nonrelevant
      metabolites from pesticides in ground and drinking water].

PMID- 19760250
TI  - [Evaluation of Germany's sixth national health target entitled "Depressive
      illnesses - prevention, early diagnosis, sustainable treatment"].
AB  - In 2006, Germany's sixth national health target entitled "Depressive illnesses -
      prevention, early diagnosis, sustainable treatment" was developed by an
      interdisciplinary group of experts. A total of six areas of activity and
      proposals for action with potential for improvement were defined. Subsequently, a
      group of experts was entrusted with designing evaluation strategies, defining
      indicators of progress, and examining the accessibility of data sources for
      evaluation. For the primary start-up activities set out in the health targets,
      specific progress indicators were deduced, and routine data available for
      evaluation were identified. As a next step, the limitations of these data sources
      were analyzed and necessary improvements described. Relevant indicators of
      progress for specific areas of activity have been described, the availability and
      usability of different existing data sources examined, and further supplements or
      additional specifications with respect to the indicators described. Due to
      inadequate data sources, additional systematic surveys are required to evaluate
      the health target and its implementation. Existing German surveys should be
      extended by questions concerning relevant measures and progress indicators;
      various progress indicators should be analyzed on a general basis.

PMID- 19760252
TI  - [What do we know about anesthetic mechanisms?: hypnosis, unresponsiveness to
      surgical incision and amnesia].
AB  - Despite the increase of molecular knowledge in anesthesia research over the past
      decades there is still ongoing discussion about the mechanisms of anesthesia.
      This article focuses on presenting anesthetic sensitive ligand and voltage gated
      ion channels. The impact on anesthetic modulated ion channels is summarized for
      clinically commonly used anesthetics isoflurane, propofol and ketamine.
      Furthermore, the anesthetic features hypnosis, unresponsiveness to surgical
      incision and amnesia and their putative relevant anatomical sites in the central
      nervous system are briefly introduced.

PMID- 19760253
TI  - No effect of prior caffeine ingestion on neuromuscular recovery after maximal
      fatiguing contractions.
AB  - The purpose of this study was to test the hypothesis that prior caffeine
      ingestion would enhance neural recovery after isometric fatiguing maximal
      intermittent plantar flexions, and thus would enhance the recovery of voluntary
      muscle strength. After a familiarisation session, 13 males randomly participated
      in two experimental trials where they ingested either caffeine (approximately 6
      mg/kg) or identical placebo pills 1 h prior to testing. Subjects were tested for
      electromyogram (EMG) activity and evoked V-waves in the soleus and gastrocnemius
      medialis muscles. These measurements were obtained during brief plantar flexion
      maximum voluntary isometric contractions (MVICs), and normalised by the
      superimposed maximal M-wave (EMG/M(SUP) and V/M(SUP), respectively), before and
      after (20 s, 10 min and 20 min) a fatigue protocol (seven 25 s MVICs, 5 s rest).
      There were no effects (P > 0.05) of caffeine ingestion on EMG/M(SUP), V/M(SUP),
      MVIC or M(SUP). The central neural modulation (EMG/M(SUP) and V/M(SUP)) and
      voluntary strength changes followed a similar time-course with a substantial
      reduction 20 s post-fatigue and a gradual return towards baseline values.

PMID- 19760254
TI  - Glutathione measurements in blood samples are influenced by oxygen saturation.

PMID- 19760255
TI  - Effect of carbohydrate ingestion on exercise performance and carbohydrate
      metabolism in persons with spinal cord injury.
AB  - Carbohydrate ingestion during exercise and as a pre-exercise bolus improves
      exercise performance in able-bodied athletes. Little is known about the potential
      for carbohydrate ingestion to improve exercise performance in athletes with
      spinal cord injury (SCI), nor the potential physiological limitations of such a
      practice resulting from an SCI. Therefore, this study investigated the effects of
      carbohydrate ingestion on exercise performance in physically active and athletic
      persons with SCI. Six participants with complete SCI (neurological level of
      lesion ranging from C(6) to T(7)) and normal glucose tolerance were studied twice
      during 60 min of arm cranking at 65% of peak oxygen consumption followed by a 20
      min time trial with the ingestion of either a carbohydrate drink (CHO trial: 0.5
      g CHO kg(-1) body weight in 500 ml) or placebo (PLA trial) applied in a double
      blind counter-balanced manner. The participants with tetraplegia had sufficient
      neurological function to permit voluntary arm-cranking exercise. There was no
      difference in time-trial performance between CHO and PLA trials (P > 0.05). The
      results suggest that carbohydrate ingestion in persons with SCI does not improve
      exercise performance.

PMID- 19760256
TI  - Functional characterization of the Arabidopsis bHLH92 transcription factor in
      abiotic stress.
AB  - In our previous microarray analysis of NaCl-treated Arabidopsis roots, we
      identified a basic-helix-loop-helix (bHLH) transcription factor, bHLH92
      (At5g43650), as one of the transcripts showing the greatest fold-increase in
      abundance upon NaCl exposure. Here, we characterize the role of bHLH92 in the
      context of abiotic stress physiology and hormone responses. We observed that
      bHLH92 transcript abundance increases in response to NaCl, dehydration, mannitol,
      and cold treatments, and compared these responses to those of two closely related
      genes: bHLH41 and bHLH42. The NaCl-inducibility of bHLH92 was only partially
      dependent on abscisic acid (ABA) biosynthesis and SALT OVERLY SENSITIVE2 (SOS2)
      pathways. As compared to WT, root elongation of bhlh92 mutants was more sensitive
      to mannitol, and these mutants also showed increased electrolyte leakage
      following NaCl treatments. Overexpression of bHLH92 moderately increased the
      tolerance to NaCl and osmotic stresses. Finally, we identified at least 19
      putative downstream target genes of bHLH92 under NaCl treatment using an
      oligonucleotide microarray. Together these data show that bHLH92 functions in
      plant responses to osmotic stresses, although the net contribution of bHLH92
      regulated genes to stress tolerance appears relatively limited in proportion to
      what might be expected from its transcript expression pattern.

PMID- 19760257
TI  - Broad clinical phenotypes associated with TAR-DNA binding protein (TARDBP)
      mutations in amyotrophic lateral sclerosis.
AB  - The finding of TDP-43 as a major component of ubiquitinated protein inclusions in
      amyotrophic lateral sclerosis (ALS) has led to the identification of 30 mutations
      in the transactive response-DNA binding protein (TARDBP) gene, encoding TDP-43.
      All but one are in exon 6, which encodes the glycine-rich domain. The aim of this
      study was to determine the frequency of TARDBP mutations in a large cohort of
      motor neurone disease patients from Northern England (42 non-superoxide dismutase
      1 (SOD1) familial ALS (FALS), nine ALS-frontotemporal dementia, 474 sporadic ALS
      (SALS), 45 progressive muscular atrophy cases). We identified four mutations, two
      of which were novel, in two familial (FALS) and two sporadic (SALS) cases, giving
      a frequency of TARDBP mutations in non-SOD1 FALS of 5% and SALS of 0.4%. Analysis
      of clinical data identified that patients had typical ALS, with limb or bulbar
      onset, and showed considerable variation in age of onset and rapidity of disease
      course. However, all cases had an absence of clinically overt cognitive
      dysfunction.

PMID- 19760258
TI  - Intratumoral patterns of clonal evolution in gliomas.
AB  - Few studies have explored the patterns of clonal evolution in gliomas. Here, we
      investigate the cytogenetic patterns of intratumoral clonal evolution of gliomas
      and their impact on tumor histopathology and patient survival. Cytogenetic
      analysis of 90 gliomas was performed in individual tumor cells (>200 cells/tumor)
      using multicolor (N = 16 probes) interphase-FISH. Overall, chromosome gains were
      more frequent than chromosome losses. Gains of chromosome 7 and/or EGFR
      amplification were detected in 91% of the cases, whereas del(9p21) (77%) and
      del(10q23) (78%) were the most frequent chromosome losses. Virtually, all cases
      (99%) showed >or=2 tumor cell clones, with higher numbers among high- versus low
      grade gliomas (p = 0.001). Nine different cytogenetic patterns were found in the
      ancestral tumor clones. In most gliomas, ancestral clones showed abnormalities of
      chromosome 7, 9p, and/or 10q and cytogenetic evolution consisted of acquisition
      of additional abnormalities followed by tetraploidization. Conversely, early
      tetraploidization was associated with low-grade astrocytomas-2/3 pilocytic and
      3/6 grade II diffuse astrocytomas-and combined loss of 1p36/19q13 with
      oligodendrogliomas, respectively; both aberrations were associated with a better
      patient outcome (p = 0.03). Overall, our results support the existence of
      different pathways of intratumoral evolution in gliomas.

PMID- 19760259
TI  - Transgenic overexpression of the alpha-synuclein interacting protein synphilin-1
      leads to behavioral and neuropathological alterations in mice.
AB  - Synphilin-1 has been identified as an interacting protein of alpha-synuclein,
      Parkin, and LRRK2, proteins which are mutated in familial forms of Parkinson
      disease (PD). Subsequently, synphilin-1 has also been shown to be an intrinsic
      component of Lewy bodies in sporadic PD. In order to elucidate the role of
      synphilin-1 in the pathogenesis of PD, we generated transgenic mice
      overexpressing wild-type and mutant (R621C) synphilin-1 driven by a mouse prion
      protein promoter. Transgenic expression of both wild-type and the R621C variant
      synphilin-1 resulted in increased dopamine levels of the nigrostriatal system in
      3-month-old mice. Furthermore, we found pathological ubiquitin-positive
      inclusions in cerebellar sections and dark-cell degeneration of Purkinje cells.
      Both transgenic mouse lines showed significant reduction of motor skill learning
      and motor performance. These findings suggest a pathological role of
      overexpressed synphilin-1 in vivo and will help to further elucidate the
      mechanisms of protein aggregation and neuronal cell death.

PMID- 19760260
TI  - Brassica orthologs from BANYULS belong to a small multigene family, which is
      involved in procyanidin accumulation in the seed.
AB  - As part of a research programme focused on flavonoid biosynthesis in the seed
      coat of Brassica napus L. (oilseed rape), orthologs of the BANYULS gene that
      encoded anthocyanidin reductase were cloned in B. napus as well as in the related
      species Brassica rapa and Brassica oleracea. B. napus genome contained four
      functional copies of BAN, two originating from each diploid progenitor. Amino
      acid sequences were highly conserved between the Brassicaceae including B. napus,
      B. rapa, B. oleracea as well as the model plant Arabidopsis thaliana. Along the
      200 bp in 5' of the ATG codon, Bna.BAN promoters (ProBna.BAN) were conserved with
      AtANR promoter and contained putative cis-acting elements. In addition,
      transgenic Arabidopsis and oilseed rape plants carrying the first 230 bp of
      ProBna.BAN fused to the UidA reporter gene were generated. In the two
      Brassicaceae backgrounds, ProBna.BAN activity was restricted to the seed coat. In
      B. napus seed, ProBna.BAN was activated in procyanidin-accumulating cells, namely
      the innermost layer of the inner integument and the micropyle-chalaza area. At
      the transcriptional level, the four Bna.BAN genes were expressed in the seed.
      Laser microdissection assays of the seed integuments showed that Bna.BAN
      expression was restricted to the inner integument, which was consistent with the
      activation profile of ProBna.BAN. Finally, Bna.BAN genes were mapped onto oilseed
      rape genetic maps and potential co-localisations with seed colour quantitative
      trait loci are discussed.

PMID- 19760261
TI  - Brassinosteroids promote photosynthesis and growth by enhancing activation of
      Rubisco and expression of photosynthetic genes in Cucumis sativus.
AB  - Brassinosteroids (BRs) are a new group of plant growth substances that promote
      plant growth and productivity. We showed in this study that improved growth of
      cucumber (Cucumis sativus) plants after treatment with 24-epibrassinolide (EBR),
      an active BR, was associated with increased CO(2) assimilation and quantum yield
      of PSII (Phi(PSII)). Treatment of brassinazole (Brz), a specific inhibitor for BR
      biosynthesis, reduced plant growth and at the same time decreased CO(2)
      assimilation and Phi(PSII). Thus, the growth-promoting activity of BRs can be, at
      least partly, attributed to enhanced plant photosynthesis. To understand how BRs
      enhance photosynthesis, we have analyzed the effects of EBR and Brz on a number
      of photosynthetic parameters and their affecting factors, including the contents
      and activity of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco).
      Northern and Western blotting demonstrated that EBR upregulated, while Brz
      downregulated, the expressions of rbcL, rbcS and other photosynthetic genes. In
      addition, EBR had a positive effect on the activation of Rubisco based on
      increased maximum Rubisco carboxylation rates (V (c,max)), total Rubisco activity
      and, to a greater extent, initial Rubisco activity. The accumulation patterns of
      Rubisco activase (RCA) based on immunogold-labeling experiments suggested a role
      of RCA in BR-regulated activation state of Rubisco. Enhanced expression of genes
      encoding other Calvin cycle genes after EBR treatment may also play a positive
      role in RuBP regeneration (J (max)), thereby increasing maximum carboxylation
      rate of Rubisco (V (c,max)). Thus, BRs promote photosynthesis and growth by
      positively regulating synthesis and activation of a variety of photosynthetic
      enzymes including Rubisco in cucumber.

PMID- 19760262
TI  - Induction of serotonin biosynthesis is uncoupled from the coordinated induction
      of tryptophan biosynthesis in pepper fruits (Capsicum annuum) upon pathogen
      infection.
AB  - It has been suggested that serotonin biosynthesis is regulated by tryptophan
      decarboxylase (TDC) in plants. To determine if TDC plays a rate-limiting role in
      serotonin biosynthesis, two TDC genes, PepTDC1 and PepTDC2, were cloned from
      pepper (Capsicum annuum L.) fruits infected with anthracnose fungus and their
      expression was then examined in various organs, including fruit that had been
      treated with the fungus or various chemicals. PepTDC1 expression was highly
      induced in pepper fruits after treatment with fungus and ethylene, while PepTDC2
      was constitutively expressed at low levels in all pepper tissues. Additionally,
      predominant induction of PepTDC1 mRNA and TDC enzyme activity was detected in the
      unripe-green fruit, but not in the ripe-red fruit upon pathogen infection. Higher
      expression of TDC in unripe-green fruit was closely associated with increased
      levels of tryptamine, serotonin, and serotonin derivatives. However, unlike the
      enhanced serotonin synthesis, tryptophan levels responded unchanged when
      challenged with the pathogen in both the unripe-green fruit and the ripe-red
      fruit. Expression of two key tryptophan biosynthetic genes, anthranilate synthase
      (ASalpha) and tryptophan synthase (TSbeta), remained unchanged in response to
      treatment. Also, anthranilate synthase enzyme activity remained steady regardless
      of pathogen infection. Taken together, these results suggest that the synthesis
      of serotonin was regulated by the induction of TDC without a simultaneous
      increase in tryptophan levels in pepper fruits.

PMID- 19760263
TI  - A WRKY transcription factor participates in dehydration tolerance in Boea
      hygrometrica by binding to the W-box elements of the galactinol synthase
      (BhGolS1) promoter.
AB  - Accumulation of compatible osmolytes, such as soluble sugars, in plants is an
      important osmoprotective mechanism. Sugars play a role in osmotic adjustment and
      are associated with stabilization of proteins and cell structures, reactive
      oxygen species scavenging, signaling functions or induction of adaptive pathways.
      Galactinol is the galactosyl donor for the synthesis of raffinose family
      oligosaccharides (RFOs) and its synthesis by galactinol synthase (GolS) is the
      first committed step of the RFOs biosynthetic pathway. GolS genes are induced by
      a variety of stresses in both stress-sensitive and tolerant-plant species;
      however, the mechanism of transcriptional regulation is not fully established. In
      this paper, we characterized a GolS gene (BhGolS1) that was dehydration and ABA
      inducible in the resurrection plant Boea hygrometrica and conferred dehydration
      tolerance in a transgenic tobacco system. Four W-box cis-elements were identified
      in the BhGolS1 promoter and shown to be bound by an early dehydration and ABA
      inducible WRKY gene (BhWRKY1). These data suggest a mechanism where BhWRKY1 is
      likely to function in an ABA-dependent signal pathway to regulate BhGolS1
      expression, which leads to the accumulation of RFOs in desiccation-tolerant B.
      hygrometrica leaves.

PMID- 19760264
TI  - Detection and characterisation of large SERPINC1 deletions in type I inherited
      antithrombin deficiency.
AB  - Methods routinely used for investigating the molecular basis of antithrombin (AT)
      deficiency do not detect large SERPINC1 rearrangements. Between 2000 and 2008, 86
      probands suspected of having AT-inherited type I deficiency were screened for
      SERPINC1 mutations in our laboratory. Mutations causally linked to the deficiency
      were identified by sequencing analysis in 63 probands. We present here results of
      multiplex ligation-dependent probe amplification (MLPA) analysis performed in 22
      of the 23 remaining probands, in whom sequencing had revealed no mutation. Large
      deletions, present at the heterozygous state, were detected in 10 patients: whole
      gene deletions in 5 and partial deletions removing either exon 6 (n = 2), exons 1
      2 (n = 1) or exons 5-7 (n = 2) in 5 others. Exon 6 partial deletions are a 2,769
      bp deletion and a 1,892-bp deletion associated with a 10-bp insertion, both
      having 5' and/or 3' breakpoints located within Alu repeat elements. In addition,
      we identified the 5' breakpoint of a previously reported deletion of exons 1-2
      within an extragenic Alu repeat. Distinct mutational mechanisms explaining these
      Alu sequence-related deletions are proposed. Overall, in this series, large
      deletions detected by MLPA explain almost half of otherwise unexplained type I AT
      inherited deficiency cases.

PMID- 19760265
TI  - Mutations in the VNTR of the carboxyl-ester lipase gene (CEL) are a rare cause of
      monogenic diabetes.
AB  - We have previously shown that heterozygous single-base deletions in the carboxyl
      ester lipase (CEL) gene cause exocrine and endocrine pancreatic dysfunction in
      two multigenerational families. These deletions were found in the first and
      fourth repeats of a variable number of tandem repeats (VNTR), which has proven
      challenging to sequence due to high GC-content and considerable length variation.
      We have therefore developed a screening method consisting of a multiplex PCR
      followed by fragment analysis. The method detected putative disease-causing
      insertions and deletions in the proximal repeats of the VNTR, and determined the
      VNTR-length of each allele. When blindly testing 56 members of the two families
      with known single-base deletions in the CEL VNTR, the method correctly assessed
      the mutation carriers. Screening of 241 probands from suspected maturity-onset
      diabetes of the young (MODY) families negative for mutations in known MODY genes
      (95 individuals from Denmark and 146 individuals from UK) revealed no deletions
      in the proximal repeats of the CEL VNTR. However, we found one Danish patient
      with a short, novel CEL allele containing only three VNTR repeats (normal range 7
      23 in healthy controls). This allele co-segregated with diabetes or impaired
      glucose tolerance in the patient's family as six of seven mutation carriers were
      affected. We also identified individuals who had three copies of a complete CEL
      VNTR. In conclusion, the CEL gene is highly polymorphic, but mutations in CEL are
      likely to be a rare cause of monogenic diabetes.

PMID- 19760266
TI  - Lysine-91 of the tetraheme c-type cytochrome CymA is essential for quinone
      interaction and arsenate respiration in Shewanella sp. strain ANA-3.
AB  - The tetraheme c-type cytochrome, CymA, is essential for arsenate respiratory
      reduction in Shewanella sp. ANA-3, a model arsenate reducer. CymA is predicted to
      mediate electron transfer from quinols to the arsenate respiratory reductase
      (ArrAB). Here, we present biochemical and physiological evidence that CymA
      interacts with menaquinol (MQH(2)) substrates. Fluorescence quench titration with
      the MQH(2) analog, 2-n-heptyl-4-hydroxyquinoline-N-oxide (HOQNO), was used to
      demonstrate quinol binding of E. coli cytoplasmic membranes enriched with various
      forms of CymA. Wild-type CymA bound HOQNO with a K (d) of 0.1-1 microM. It was
      also shown that the redox active MQH(2) analog, 2,3-dimethoxy-1,4-naphthoquinone
      (DMNH(2)), could reduce CymA in cytoplasmic membrane preparations. Based on a
      CymA homology model made from the NrfH tetraheme cytochrome structure, it was
      predicted that Lys91 would be involved in CymA-quinol interactions. CymA with a
      K91Q substitution showed little interaction with HOQNO. In addition, DMNH(2)
      dependent reduction of CymA-K91Q was diminished by 45% compared to wild-type
      CymA. A DeltacymA ANA-3 strain containing a plasmid copy of cymA-K91Q failed to
      grow with arsenate as an electron acceptor. These results suggest that Lys91 is
      physiologically important for arsenate respiration and support the hypothesis
      that CymA interacts with menaquinol resulting in the reduction of the cytochrome.

PMID- 19760267
TI  - Why do humans make antisaccade errors?
AB  - Antisaccade errors are attributed to failure to inhibit the habitual prosaccade.
      We investigated whether the amount of information about the required response the
      patient has before the trial begins also contributes to error rate. Participants
      performed antisaccades in five conditions. The traditional design had two goals
      on the left and right horizontal meridians. In the second condition, stimulus
      goal confusability between trials was eliminated by displacing one goal upward.
      In the third, hemifield uncertainty was eliminated by placing both goals in the
      same hemifield. In the fourth, goal uncertainty was eliminated by having only one
      goal, but interspersed with no-go trials. The fifth condition eliminated all
      uncertainty by having the same goal on every trial. Antisaccade error rate
      increased by 2% with each additional source of uncertainty, with the main effect
      being hemifield information, and a trend for stimulus-goal confusability. A
      control experiment for the effects of increasing angular separation between
      targets without changing these types of prior response information showed no
      effects on latency or error rate. We conclude that other factors besides
      prosaccade inhibition contribute to antisaccade error rates in traditional
      designs, possibly by modulating the strength of goal activation.

PMID- 19760268
TI  - Presaccadic attention interferes with feature detection.
AB  - Preparing a saccadic eye movement to a particular spatial location enhances the
      perception of visual targets at this location and decreases perception of nearby
      targets prior to movement onset. This effect has been termed the orientation of
      pre-saccadic attention. Here, we investigated whether pre-saccadic attention
      influenced the detection of a simple visual feature-a process that has been
      hypothesized to occur without the need for attention. Participants prepared a
      saccade to a cued location and detected the occurrence of a "pop-out" feature
      embedded in distracters at the same or different location. The results show that
      preparing a saccade to a given location decreased detection of features at non
      aimed-for locations, suggesting that the selection of a location as the next
      saccade endpoint influences sensitivity to basic visual features across the
      visual field.

PMID- 19760269
TI  - In search of differences between the two types of sensory cells innervating
      spider slit sensilla (Cupiennius salei Keys.).
AB  - The metatarsal lyriform organ of the spider Cupiennius salei is a vibration
      detector consisting of 21 cuticular slits supplied by two sensory cells each, one
      ending in the outer and the other at the inner slit membrane. In search of
      functional differences between the two cell types due to differences in stimulus
      transmission, we analyzed (1) the adaptation of responses to electrical
      stimulation, (2) the thresholds for mechanical stimulation and (3) the
      representation of male courtship vibrations using intracellular recording and
      staining techniques. Single- and multi-spiking receptor neurons were found among
      both cell types, which showed high-pass filter characteristics. Below 100-Hz
      threshold, tarsal deflections were between 1 degrees and 10 degrees. At higher
      frequencies, they decreased down to values as small as 0.05 degrees,
      corresponding to 4.5-nm tarsal deflection in the most sensitive cases. Different
      slits in the organ and receptor cells with slow or fast adaptation did not differ
      in this regard. When stimulated with male courtship vibrations, both types of
      receptor cells again did not differ significantly regarding number of action
      potentials, latency and synchronization coefficients. Surprisingly, the
      differences in dendrite coupling were not reflected by the physiological
      responses of the two cell types innervating the slits.

PMID- 19760270
TI  - Differential adaptation of high- and low-chill dormant peaches in winter through
      aquaporin gene expression and soluble sugar content.
AB  - Plants have their own mechanisms for overcoming various stresses. In cold
      regions, plants are subject to stress and must enter an inherent dormancy,
      through several complex mechanisms, if they are to continue to exist. In winter,
      regulation of tonoplast and plasma membrane aquaporin genes differed in the bud
      cushions of the high-chill peach (Prunus persica L. Batsch) cv. Kansuke Hakuto
      and the low-chill peach cv. Coral. In December and January, when the temperature
      was lowest (around 2 degrees C), the increased expression of Pp-gammaTIP1 and Pp
      PIP1 seen in the bud cushions of Kansuke Hakuto may have been related to the
      concomitant high-soluble sugar content of the cushions of this cultivar. This
      relationship may have made the cells highly stable and relatively unaffected by
      low-temperature stress owing to the presence of "glasses" that prevented ice
      nucleation. However, a simpler form of cold protection regulation seemed to occur
      in Coral, in which there was no winter increase in Pp-gammaTIP1 and Pp-PIP1 mRNA
      and a slow decline in total soluble sugar content in December and January. These
      results suggested that Pp-gammaTIP1 and Pp-PIP1, respectively, play important
      roles in intra- and intercellular membrane transport, enhancing cold resistance
      in the bud cushions of high-chill cultivars. In addition, Pp-deltaTIP1 and Pp
      PIP2 mRNA increased at the end of endodormancy in both cultivars. This change may
      be induced by endodormancy-release signals and the resumption of bud activity in
      both cultivars.

PMID- 19760271
TI  - Scoliosis in Duchenne's muscular dystrophy: a changing trend in surgical
      management : a historical surgical outcome study comparing sublaminar, hybrid and
      pedicle screw instrumentation systems.
AB  - A non-randomised retrospective study to compare the results of surgical
      correction of scoliosis in Duchenne's muscular dystrophy (DMD) patients using
      three different instrumentation systems-Sublaminar instrumentation system (Group
      A), a hybrid of sublaminar and pedicle screw systems (Group B) and pedicle screw
      system alone (Group C). Between 1993 and 2003, 43 patients with DMD underwent
      posterior spinal fusion and instrumentation. Group A (n = 19) had sublaminar
      instrumentation system, Group B (n = 13) had a hybrid construct and Group C (n =
      11) was treated with pedicle system. The mean blood loss in Group A was 4.1 l,
      3.2 l in Group B and 2.5 l in Group C. Average operating times in Group A, B and
      C were 300, 274 and 234 min, respectively. Mean pre-operative, post-operative and
      final Cobb angle in Group A was 50.05 +/- 15.46 degrees , 15.68 +/- 11.23 degrees
      and 21.57 +/- 11.63 degrees , Group B was 17.76 +/- 8.50 degrees , 3.61 +/- 2.53
      degrees and 6.69 +/- 4.19 degrees and Group C was 25.81 +/- 9.94 degrees , 5.45
      +/- 3.88 degrees , 8.90 +/- 5.82 degrees , respectively. Flexibility index or the
      potential correction calculated from bending radiographs were 60 +/- 6.33, 70 +/-
      4.65 and 67 +/- 6.79% for Group A, Group B and Group C respectively. The
      percentage correction achieved was 72.5 +/- 14.5% in Group A, 82 +/- 6% in Group
      B and 82 +/- 8% in Group C. The difference between percentage correction achieved
      and the flexibility index was 12.45 +/- 8.22, 12.05 +/- 1.3 and 15.00 +/- 1.21%
      in Group A, B and C, respectively The percentage loss of correction in Cobb
      angles at final follow-up in Group A, B and C was 12.5 +/- 3.5, 16.5 +/- 1. and
      12.5 +/- 2.5%, respectively. Complications seen in Group A were three cases of
      wound infection and two cases of implant failure; Group B had a single case of
      implant failure and Group C had one patient with wound infection and one case
      with a partial screw pull out. Early surgery and smaller curve corrections
      appears to be the current trend in the management of scoliosis in DMD. This has
      been possible due to early curve detection and surgery thus having the advantage
      of less post-operative respiratory complications and stay in paediatric intensive
      care. Also, early surgery avoids development of pelvic deformity and extension of
      instrumentation to the pelvis thereby reducing blood loss. This trend reflects
      the advent of newer and safer instrumentation systems, advanced techniques in
      anaesthesia and cord monitoring. Sublaminar instrumentation system group had
      increased operating times and blood loss compared to both the hybrid and pedicle
      screw instrumentation systems due to increased bleeding from epidural vessels and
      pelvic instrumentation. Overall, the three instrumentation constructs appear to
      provide and maintain an optimal degree of correction at medium to long term
      follow up but the advantages of lesser blood loss and surgical time without the
      need for pelvic fixation seem to swing the verdict in favour of the pedicle screw
      system.

PMID- 19760272
TI  - Frequency-dependent reproductive success in female common lizards: a real-life
      hawk-dove-bully game?
AB  - Alternative strategies are characterised by context-dependent fitness payoffs,
      which means that their fitness depends on the frequency and the nature of their
      interactions with one or more strategies. The analysis of the variation of the
      fitness of each strategy in different social environments can elucidate the
      evolutionary dynamics played by the strategies. In the common lizard, three
      female colour types (yellow, orange and mixed) are associated with alternative
      reaction norms in reproduction and social behaviour that signal alternative
      strategies. To clarify the nature of colour-specific interactions and their
      influence on female fitness, we analysed the response of female reproductive
      success to an experimental manipulation of colour frequencies in natural
      populations. We found that juvenile body condition at birth for all colour types
      was negatively affected by the local frequency of yellow females. In addition, we
      found that mixed females had higher clutch hatching success in the populations
      where orange females were frequent. These results prove that female reproduction
      is sensitive to the social environment, and are consistent with a scenario of a
      hawk-dove-bully game, in which yellow females are aggressive hawks, orange
      females non-aggressive doves, and mixed females have a context-dependent bully
      strategy. In this system, the plastic bully strategy would confer a reproductive
      advantage to putative heterozygotes in some social environments, which could
      allow the maintenance of the system through context-dependent overdominance
      effects.

PMID- 19760273
TI  - Inhibition of IK,ACh current may contribute to clinical efficacy of class I and
      class III antiarrhythmic drugs in patients with atrial fibrillation.
AB  - Inward rectifier potassium currents I(K1) and acetylcholine activated I(K,ACh)
      are implicated in atrial fibrillation (AF) pathophysiology. In chronic AF (cAF),
      I(K,ACh) develops a receptor-independent, constitutively active component that
      together with increased I(K1) is considered to support maintenance of AF. Here,
      we tested whether class I (propafenone, flecainide) and class III (dofetilide,
      AVE0118) antiarrhythmic drugs inhibit atrial I(K1) and I(K,ACh) in patients with
      and without cAF. I(K1) and I(K,ACh) were measured with voltage clamp technique in
      atrial myocytes from 58 sinus rhythm (SR) and 35 cAF patients. The M-receptor
      agonist carbachol (CCh; 2 microM) was employed to activate I(K,ACh). In SR, basal
      current was not affected by either drug indicating no effect of these compounds
      on I(K1). In contrast, all tested drugs inhibited CCh-activated I(K,ACh) in a
      concentration-dependent manner. In cAF, basal current was confirmed to be larger
      than in SR (at -80 mV, -15.2 +/- 1.2 pA/pF, n = 88/35 vs. -6.5 +/- 0.4 pA/pF, n =
      194/58 [myocytes/patients]; P < 0.05), whereas CCh-activated I(K,ACh) was smaller
      (-4.1 +/- 0.5 pA/pF vs. -9.5 +/- 0.6 pA/pF; P < 0.05). In cAF, receptor
      independent constitutive I(K,ACh) contributes to increased basal current, which
      was reduced by flecainide and AVE0118 only. This may be due to inhibition of
      constitutively active I(K,ACh) channels. In cAF, all tested drugs reduced CCh
      activated I(K,ACh). We conclude that in cAF, flecainide and AVE0118 reduce
      receptor-independent, constitutively active I(K,ACh), suggesting that they may
      block I(K,ACh) channels, whereas propafenone and dofetilide likely inhibit M
      receptors. The efficacy of flecainide to terminate AF may in part result from
      blockade of I(K,ACh).

PMID- 19760274
TI  - Es kann die Spur von unseren Erdetagen--on pharmacologists and pharmacology.
AB  - Es kann die Spur von unseren Erdetagen is a slightly modified line from Goethe's
      tragedy Faust and together with the following line can be translated as "The
      vestiges of our path on earth/Through aeons cannot fade away". The author's
      festival speech at the 50th Spring Meeting of the German Pharmacological Society
      this year in Mainz was given under that title and is presented here in abridged
      form. Twelve examples are given showing that indeed our, the pharmacologists',
      professional vestiges cannot disappear. Many pharmacologists may share this view
      of their profession.

PMID- 19760275
TI  - Magnetoreception in birds: no intensity window in "fixed direction" responses.
AB  - Under 502 nm turquoise light combined with 590 nm yellow light and in total
      darkness, European robins, Erithacus rubecula, no longer prefer their migratory
      direction, but exhibit so-called fixed direction responses that do not show the
      seasonal change between spring and autumn. We tested robins under these light
      conditions in the local geomagnetic field of 46 microT, a field of twice this
      intensity, 92 microT, and a field of three times this intensity, 138 microT.
      Under all three magnetic conditions, the birds preferred the same easterly
      direction under turquoise-and-yellow light and the same northwesterly direction
      under dark, while they were oriented in their seasonally appropriate direction
      under control conditions. "Fixed direction" responses are thus not limited to a
      narrow intensity window as has been found for normal compass orientation. This
      can be attributed to their origin in the magnetite-based receptor in the upper
      beak, which operates according to fundamentally different principles than the
      radical pair mechanism in the retina mediating compass orientation. "Fixed
      direction" responses are possibly a relict of a receptor mechanism that changed
      its function, now mainly providing information on magnetic intensity.

PMID- 19760276
TI  - Darwin's warm little pond revisited: from molecules to the origin of life.
AB  - All known cosmic and geological conditions and laws of chemistry and
      thermodynamics allow that complex organic matter could have formed spontaneously
      on pristine planet Earth about 4,000 mya. Simple gasses and minerals on the
      surface and in oceans of the early Earth reacted and were eventually organized in
      supramolecular aggregates and enveloped cells that evolved into primitive forms
      of life. Chemical evolution, which preceded all species of extant organisms, is a
      fact. In this review, we have concentrated on experimental and theoretical
      research published over the last two decades, which has added a wealth of new
      details and helped to close gaps in our previous understanding of this
      multifaceted field. Recent exciting progress in the molecular and genetic
      analyses of existing life, in particular microorganisms of ancient origin, even
      supports the possibility that a cellular, self-reproducing common ancestor might
      be assembled and resurrected in anaerobic cultures at some time in the future.
      Charles Darwin did not, and indeed, could not, address and specify the earliest
      phases of life which preceded the Origin of Species. However, in a famous letter,
      he sketched "a warm little pond with all sorts of... (chemicals, in which) ...a
      protein was chemically formed." We try to trace the impact of his charming clear
      sighted metaphor up to the present time.

PMID- 19760277
TI  - Charles Darwin, beetles and phylogenetics.
AB  - Here, we review Charles Darwin's relation to beetles and developments in
      coleopteran systematics in the last two centuries. Darwin was an enthusiastic
      beetle collector. He used beetles to illustrate different evolutionary phenomena
      in his major works, and astonishingly, an entire sub-chapter is dedicated to
      beetles in "The Descent of Man". During his voyage on the Beagle, Darwin was
      impressed by the high diversity of beetles in the tropics, and he remarked that,
      to his surprise, the majority of species were small and inconspicuous. However,
      despite his obvious interest in the group, he did not get involved in beetle
      taxonomy, and his theoretical work had little immediate impact on beetle
      classification. The development of taxonomy and classification in the late
      nineteenth and earlier twentieth century was mainly characterised by the
      exploration of new character systems (e.g. larval features and wing venation). In
      the mid-twentieth century, Hennig's new methodology to group lineages by derived
      characters revolutionised systematics of Coleoptera and other organisms. As
      envisioned by Darwin and Ernst Haeckel, the new Hennigian approach enabled
      systematists to establish classifications truly reflecting evolution. Roy A.
      Crowson and Howard E. Hinton, who both made tremendous contributions to
      coleopterology, had an ambivalent attitude towards the Hennigian ideas. The
      Mickoleit school combined detailed anatomical work with a classical Hennigian
      character evaluation, with stepwise tree building, comparatively few characters
      and a priori polarity assessment without explicit use of the outgroup comparison
      method. The rise of cladistic methods in the 1970s had a strong impact on beetle
      systematics. Cladistic computer programs facilitated parsimony analyses of large
      data matrices, mostly morphological characters not requiring detailed anatomical
      investigations. Molecular studies on beetle phylogeny started in the 1990s with
      modest taxon sampling and limited DNA data. This has changed dramatically. With
      very large data sets and high throughput sampling, phylogenetic questions can be
      addressed without prior knowledge of morphological characters. Nevertheless,
      molecular studies have not lead to the great breakthrough in beetle systematics-
      yet. Especially the phylogeny of the extremely species rich suborder Polyphaga
      remains incompletely resolved. Coordinated efforts of molecular workers and of
      morphologists using innovative techniques may lead to more profound insights in
      the near future. The final aim is to develop a well-founded phylogeny, which
      truly reflects the evolution of this immensely species rich group of organisms.

PMID- 19760278
TI  - Cancer stem cells: controversies in multiple myeloma.
AB  - Increasing data suggest that the initiation, relapse, and progression of human
      cancers are driven by specific cell populations within an individual tumor.
      However, inconsistencies have emerged in precisely defining phenotypic markers
      that can reliably identify these "cancer stem cells" in nearly every human
      malignancy studied to date. Multiple myeloma, one of the first tumors postulated
      to be driven by a rare population of cancer stem cells, is no exception. Similar
      to other diseases, controversy surrounds the exact phenotype and biology of
      multiple myeloma cells with the capacity for clonogenic growth. Here, we review
      the studies that have led to these controversies and discuss potential reasons
      for these disparate findings. Moreover, we speculate how these inconsistencies
      may be resolved through studies by integrating advancements in both myeloma and
      stem cell biology.

PMID- 19760279
TI  - Tumor necrosis in osteosarcoma: inclusion of the point of greatest metabolic
      activity from F-18 FDG PET/CT in the histopathologic analysis.
AB  - OBJECTIVE: To determine if the location of the point of maximum standardized
      uptake value (SUVmax) being included in or not included in the histopathologic
      slab section corresponded to tumor necrosis or survival. MATERIALS AND METHODS:
      Twenty-nine osteosarcoma patients underwent post-chemotherapy [fluorine-18]
      fluoro-2-deoxy-D: -glucose (FDG) positron-emission tomography-computed tomography
      (PET/CT) prior to resection. PET/CT images were correlated with slab-section
      location as determined by photographs or knowledge of specimen processing. The
      location of the point of SUVmax was then assigned as being 'in' or 'out' of the
      slab section. Cox's proportional hazard regression was used to evaluate
      relationships between the location and value of SUVmax and survival. Logistic
      regression was employed to evaluate tumor necrosis. RESULTS: No correlation was
      found between the SUVmax location and survival or tumor necrosis. High SUVmax
      correlated to poor survival. CONCLUSION: High SUVmax value correlated to poor
      survival. Minimal viable tumor (> 10%) following chemotherapy is a known
      indicator of poor survival. No correlation was found between the location of
      SUVmax and survival or tumor necrosis. Therefore, the SUVmax value either does
      not correspond to a sufficient number of tumor cells to influence tumor necrosis
      measurement or it was included in the out-of-slab samples that were directed to
      viable-appearing areas of the gross specimen. Since high SUVmax has been
      previously found to correspond to poor tumor necrosis, and tumor necrosis is
      simply an estimate of the amount of viable tumor, SUVmax likely represents many
      viable tumor cells. Therefore, when not in the slab section, SUVmax was likely
      included in the tumor necrosis measurement through directed sampling, validating
      our current method of osteosarcoma specimen analysis.

PMID- 19760280
TI  - Electrophysiological deficits in the retina of the DBA/2J mouse.
AB  - The DBA/2J (D2J) is a genetic mouse model for glaucomatous neurodegeneration
      because the animals develop anatomical and functional retinal deficits that
      partially can be correlated with elevated intraocular pressure (IOP). The IOP
      starts to increase at an age of about 6 months as a result of morphological
      changes within the anterior eye segment, e.g., pigment dispersion and iris
      synechiae. The purpose of the present study was to investigate how ERG responses
      change in individuals at different ages in D2J mice and to compare these changes
      with normal aging effects in pigmented C57/B6 (B6) mice. IOP was measured in
      awake, non-sedated D2J and B6 mice with a rebound tonometer. At ages between 2-3
      and 10 months, scotopic flash ERGs were measured five times with about 2 months'
      intervals. In addition, light adapted flicker ERGs were recorded. Our data show
      that the D2J shows lower flicker ERG responses than the B6 mice already at an age
      of 2-3 months. Dark adapted flash ERG responses are not decreased at this age. In
      both mouse strains the ERG responses decrease as a function of age, but there is
      a stronger decrease in the D2J mice. The data of flicker ERGs suggest the
      presence of early functional deficits in the D2J retina that possibly have a post
      receptoral origin. The scotopic flash ERG reveals a functional deficit that
      occurs at a later stage and that possibly is IOP dependent. But, the deficits
      appear at an age at which the IOP is still lower than in the B6 mouse, indicating
      that other factors play an additional role.

PMID- 19760281
TI  - Bupropion and nicotine enhance responding for nondrug reinforcers via dissociable
      pharmacological mechanisms in rats.
AB  - RATIONALE: Nicotine serves as a primary reinforcer but also potently enhances
      responding for nonnicotine stimuli with reinforcing properties. One of the most
      successful pharmacotherapies for smoking cessation, bupropion, also increases
      responding for nondrug reinforcers such as food and brain stimulation rewards.
      OBJECTIVE: The present studies investigated whether treatment with bupropion and
      nicotine had similar effects on responding for a reinforcing visual stimulus
      (VS). They also investigated whether the effects of bupropion and nicotine
      depended on common pharmacological substrates. RESULTS: Nicotine (0.4 mg/kg base)
      enhanced responding for the VS, and this enhancing effect increased across
      testing sessions, replicating our previous findings. Bupropion (3, 10, and 30
      mg/kg salt) dose-dependently increased responding for the VS. Treatment with 10
      and 30 mg/kg bupropion resulted in a profile similar to nicotine; operant
      responding increased over repeated drug treatments. The reinforcement enhancing
      effect of nicotine, but not bupropion, was blocked by pretreatment with the
      nicotinic acetylcholine receptor antagonist mecamylamine. In contrast, the
      reinforcement enhancing effect of bupropion, but not nicotine, was blocked by
      pretreatment with the alpha noradrenergic antagonist prazosin. CONCLUSION: The
      reinforcement enhancing effects of nicotine and bupropion increased over time and
      repeated treatments suggesting a shared mechanism of action. However, the
      reinforcement enhancing effects of nicotine are mediated by nicotinic
      acetylcholine receptors, whereas the reinforcement enhancing effects of bupropion
      were mediated by alpha noradrenergic receptors.

PMID- 19760282
TI  - Chronic therapy with citalopram decreases regional cerebral glucose utilization
      in OBX, and not sham-operated, rats: an autoradiographic study.
AB  - RATIONALE: Chronic treatment with the selective serotonin reuptake inhibitor,
      citalopram, normalizes several behavioral and neurochemical abnormalities in the
      olfactory bulbectomized (OBX) rat model of depression. OBJECTIVE: To assess the
      changes in regional cerebral glucose utilization (rCGU) following chronic
      treatment with citalopram in OBX and sham-operated rats. METHODS: Male Sprague
      Dawley rats (160-190 g) were used. Two weeks following the surgeries, the rats
      were implanted with osmotic minipumps which delivered 10 mg/kg/day of citalopram
      (the sham-CTP and OBX-CTP groups) or saline (to the sham-SAL and OBX-SAL groups)
      for 2 weeks. Following the treatment, the rates of rCGU were determined in 43
      brain regions using 2-[(14)C]deoxyglucose (2-[(14)C]DG) autoradiography. RESULTS:
      The general linear model statistical analysis revealed significantly lower rCGU
      in the OBX-SAL group compared to the sham-SAL group in the medial prefrontal
      cortex and the median forebrain bundle. The sham-CTP group had significantly
      lower rCGU relative to the sham-SAL group in the medial prefrontal cortex. The
      OBX-CTP group had significantly lower rCGU than the OBX-SAL group in the anterior
      olfactory nucleus, orbitofrontal cortex, frontal cortex, anterior cingulate
      cortex, visual cortex, and substantia nigra--pars reticulata. The rCGU in the OBX
      CTP group was significantly lower than that in the sham-CTP group in the anterior
      olfactory nucleus, orbitofrontal cortex, visual cortex, and substantia nigra-
      pars reticulata. CONCLUSION: The results imply that chronic citalopram treatment,
      shown previously to result in behavioral normalization in OBX rats, establishes a
      new pattern of rCGU, rather than normalizing it to the pattern of the sham-CTP
      rats.

PMID- 19760283
TI  - Caffeine expectancies influence the subjective and behavioral effects of
      caffeine.
AB  - OBJECTIVES: This study investigated the independent and interactive effects of
      caffeine pharmacology and expected effects of caffeine on performance and
      subjective outcomes. METHODS: Abstinent coffee drinkers (n = 60) consumed
      decaffeinated coffee with either 280 mg or 0 mg added caffeine. Caffeine dose was
      crossed with varying instructions that the coffee would either enhance or impair
      performance in a 2 x 2 factorial design. Performance, mood, caffeine withdrawal,
      and negative somatic effects were assessed. RESULTS: Relative to placebo,
      caffeine improved reaction time and accuracy on the rapid visual information
      processing task, a measure of vigilance. However, there was a significant dose by
      expectancy interaction that revealed that among participants given placebo
      coffee, "impair" instructions produced better performance than "enhance"
      instructions. Caffeine also improved psychomotor performance as indicated by a
      finger tapping task with no main effects of expectancy or interactions. Impair
      instructions produced greater reports of negative somatic effects than enhance
      instructions, but only when caffeine was administered. CONCLUSIONS: Manipulating
      the expected effects of caffeine altered the behavioral and subjective effects of
      caffeine. A significant dose by expectancy interaction revealed a somewhat
      paradoxical outcome in the placebo conditions whereby those told "impair"
      performed better than those told "enhance." This may reflect compensatory
      responding as has been observed in similar studies using alcohol (Fillmore et al.
      Psychopharmacology 115:383-388, 1994). Impair instructions led to greater
      negative somatic effects only when caffeine was administered supporting the
      active placebo hypothesis.

PMID- 19760284
TI  - The role of mitochondrial uncoupling proteins in lifespan.
AB  - The increased longevity in modern societies raised the attention to biological
      interventions that could promote a healthy aging. Mitochondria are main
      organelles involved in the production of adenosine triphosphate (ATP), the
      energetic substrate for cellular biochemical reactions. The production of ATP
      occurs through the oxidative phosphorylation of intermediate substrates derived
      from the breakdown of lipids, sugars, and proteins. This process is coupled to
      production of oxygen reactive species (ROS) that in excess will have a
      deleterious role in cellular function. The damage promoted by ROS has been
      emphasized as one of the main processes involved in senescence. In the last
      decades, the discovery of specialized proteins in the mitochondrial inner
      membrane that promote the uncoupling of proton flux (named uncoupling proteins
      UCPs) from the ATP synthase shed light on possible mechanisms implicated in the
      buffering of ROS and consequently in the process of aging. UCPs are responsible
      for a physiological uncoupling that leads to decrease in ROS production inside
      the mitochondria. Thus, induction of uncoupling through UCPs could decrease the
      cellular damage that occurs during aging due to excess of ROS. This review will
      focus on the evidence supporting these mechanisms.

PMID- 19760286
TI  - Development of the Berlin Symptom Checklist Ovary (BSCL-O) for the measurement of
      quality of life of patients with primary and recurrent ovarian cancer: results of
      a phase I and II study.
AB  - GOALS OF WORK: Quality of life (Qol) represents a relevant end point in the
      clinical management of advanced ovarian cancer (AOC). However, there exist only a
      few specific instruments which have been designed for patients with ovarian
      cancer. The aim of this study was to develop a systematic checklist (Berlin
      Symptom Checklist Ovary (BSCL-O)) as an instrument of Qol for patients with AOC
      and to discriminate between the frequency and the importance of symptoms.
      PATIENTS AND METHODS: The main symptoms were identified in a phase I study via
      free interviews of five patients with ovarian cancer (OC) as well as five medical
      doctors, family dependent, and care workers. In the phase II study, the
      capability of BSCL-O was evaluated by questionnaire-guided interviews of 200
      patients with primary OC, recurrent OC, metastasized breast cancer, and benign
      ovarian tumors. MAIN RESULTS: In phase I, 36 main symptoms were identified. In
      phase II, 7,200 answers from 98.5% of all patients were evaluable. Of the 36
      symptoms of the BSCL-O, 23 revealed clinical relevance. There was a correlation
      of frequency and importance of symptoms (p < 0.05). The symptoms of the BSCL-O
      were deemed twice as strenuous in patients with recurrent OC. CONCLUSIONS: The
      BSCL-O can measure Qol of patients with OC. The BSCL-O is being validated in a
      phase III study.

PMID- 19760287
TI  - Inherited cavernous malformations of the central nervous system: clinical and
      genetic features in 19 Swiss families.
AB  - Cavernous malformations (CCMs) are benign, well-circumscribed, and mulberry-like
      vascular malformations that may be found in the central nervous system in up to
      0.5% of the population. Cavernous malformations can be sporadic or inherited. The
      common symptoms are epilepsy, hemorrhages, focal neurological deficits, and
      headaches. However, CCMs are often asymptomatic. The familiar form is associated
      with three gene loci, namely 7q21-q22 (CCM1), 7p13-p15 (CCM2), and 3q25.2-q27
      (CCM3) and is inherited as an autosomal dominant trait with incomplete
      penetrance. The CCM genes are identified as Krit 1 (CCM1), MGC4607 (CCM2), and
      PDCD10 (CCM3). Here, we present the clinical and genetic features of CCMs in 19
      Swiss families. Furthermore, surgical aspects in such families are also
      discussed.

PMID- 19760288
TI  - Angiogenic properties of adult human thymus fat.
AB  - The endogenous proangiogenic properties of adipose tissue are well recognized.
      Although the adult human thymus has long been known to degenerate into fat
      tissue, it has never been considered as a potential source of angiogenic factors.
      We have investigated the expression of diverse angiogenic factors, including
      vascular endothelial growth factor A and B, angiopoietin 1, and tyrosine-protein
      kinase receptor-2 (an angiopoietin receptor), and then analyzed their
      physiological role on endothelial cell migration and proliferation, two relevant
      events in angiogenesis. The detection of the gene and protein expression of the
      various proteins has been performed by immunohistochemistry, Western blotting,
      and quantitative real-time polymerase chain reaction. We show, for the first
      time, that adult thymus fat produces a variety of angiogenic factors and induces
      the proliferation and migration of human umbilical cord endothelial cells. Based
      on these findings, we suggest that this fat has a potential angiogenic function
      that might affect thymic function and ongoing adipogenesis within the thymus.

PMID- 19760291
TI  - Combined use of fasting plasma glucose and glycated hemoglobin A1c in the
      screening of diabetes and impaired glucose tolerance.
AB  - The aim of this study is to assess the validity of combined use of fasting plasma
      glucose (FPG) and glycated hemoglobin A1c (HbA1c) as screening tests for diabetes
      and impaired glucose tolerance (IGT) in high-risk subjects. A total of 2,298
      subjects were included. All subjects underwent a 75-g oral glucose tolerance test
      (OGTT) and HbA1c measurement. Receiver operating characteristic curve (ROC curve)
      analysis was used to examine the sensitivity and specificity of FPG and HbA1c for
      detecting diabetes and IGT, which was defined according to the 1999 World Health
      Organization (WHO) criteria. (1) Based on the ROC curve, the optimal cut point of
      FPG related to diabetes diagnosed by OGTT was 6.1 mmol/l that was associated with
      a sensitivity and specificity of 81.5 and 81.0%, respectively; The optimal cut
      point of HbA1c related to diabetes diagnosed by OGTT was 6.1%, which was
      associated with a sensitivity and specificity of 81.0 and 81.0%, respectively;
      The screening model using FPG > or = 6.1 mmol/l or HbA1c > or = 6.1% had
      sensitivity of 96.5% for detecting undiagnosed diabetes; the screening model
      using FPG > or = 6.1 mmol/l and HbA1c > or = 6.1% had specificity of 96.3% for
      detecting undiagnosed diabetes. (2) Based on the ROC curve, the optimal cut point
      of FPG related to IGT diagnosed by OGTT was 5.6 mmol/l that was associated with a
      sensitivity and specificity of 64.1 and 65.4%, respectively; The optimal cut
      point of HbA1c related to IGT diagnosed by OGTT was 5.6%, which was associated
      with a sensitivity and specificity of 66.2 and 51.0%, respectively; The screening
      model using FPG > or = 5.6 mmol/l or HbA1c > or = 5.6% had sensitivity of 87.9%
      for detecting undiagnosed IGT; The screening model using FPG > or = 5.6 mmol/l
      and HbA1c > or = 5.6% had specificity of 82.4% for detecting undiagnosed IGT.
      Compared with FPG or HbA1c alone, the simultaneous measurement of FPG and HbA1c
      (FPG and/or HbA1C) might be a more sensitive and specific screening tool for
      identifying high-risk individuals with diabetes and IGT at an early stage.

PMID- 19760292
TI  - Validation of results from knowledge discovery: mass density as a predictor of
      breast cancer.
AB  - The purpose of our study is to identify and quantify the association between high
      breast mass density and breast malignancy using inductive logic programming (ILP)
      and conditional probabilities, and validate this association in an independent
      dataset. We ran our ILP algorithm on 62,219 mammographic abnormalities. We set
      the Aleph ILP system to generate 10,000 rules per malignant finding with a recall
      >5% and precision >25%. Aleph reported the best rule for each malignant finding.
      A total of 80 unique rules were learned. A radiologist reviewed all rules and
      identified potentially interesting rules. High breast mass density appeared in
      24% of the learned rules. We confirmed each interesting rule by calculating the
      probability of malignancy given each mammographic descriptor. High mass density
      was the fifth highest ranked predictor. To validate the association between mass
      density and malignancy in an independent dataset, we collected data from 180
      consecutive breast biopsies performed between 2005 and 2007. We created a
      logistic model with benign or malignant outcome as the dependent variable while
      controlling for potentially confounding factors. We calculated odds ratios based
      on dichomotized variables. In our logistic regression model, the independent
      predictors high breast mass density (OR 6.6, CI 2.5-17.6), irregular mass shape
      (OR 10.0, CI 3.4-29.5), spiculated mass margin (OR 20.4, CI 1.9-222.8), and
      subject age (beta = 0.09, p < 0.0001) significantly predicted malignancy. Both
      ILP and conditional probabilities show that high breast mass density is an
      important adjunct predictor of malignancy, and this association is confirmed in
      an independent data set of prospectively collected mammographic findings.

PMID- 19760293
TI  - Analysis of the glomerular basement membrane in images of renal biopsies using
      the split-and-merge method: a pilot study.
AB  - Abnormal thinning, thickening, or variation in the thickness of the glomerular
      basement membrane (GBM) are caused by familial hematuria, diabetes mellitus, and
      Alport syndrome, respectively. We propose a semi-automated procedure for the
      segmentation and analysis of the thickness of the GBM in images of renal biopsy
      samples obtained by using a transmission electron microscope (TEM). The procedure
      includes the split-and-merge algorithm, morphological image processing,
      skeletonization, and statistical analysis of the width of the GBM. The procedure
      was tested with 34 TEM images of six patients. The mean and standard deviation of
      the GBM width for a patient with normal GBM were estimated to be 368 +/- 177 nm,
      those for a patient with thin GBM associated with familial hematuria were 216 +/-
      95 nm, and those for a patient with thick GBM due to diabetic nephropathy were
      1,094 +/- 361 nm. Comparative analysis of the results of image processing with
      manual measurements by an experienced renal pathologist indicated low error in
      the range of 12 +/- 9 nm.

PMID- 19760294
TI  - A case tracking system with electronic medical record integration to automate
      outcome tracking for radiologists.
AB  - Radiologists make many diagnoses, but only sporadically get feedback on the
      subsequent clinical courses of their patients. We have created a web-based
      application that empowers radiologists to create and maintain personal databases
      of cases of interest. This tool integrates with existing information systems to
      minimize manual input such that radiologists can quickly flag cases for further
      follow-up without interrupting their clinical work. We have integrated this case
      tracking system with an electronic medical record aggregation and search tool. As
      a result, radiologists can learn the outcomes of their patients with much less
      effort. We intend this tool to aid radiologists in their own personal quality
      improvement and to increase the efficiency of both teaching and research. We also
      hope to develop the system into a platform for systematic, continuous,
      quantitative monitoring of performance in radiology.

PMID- 19760296
TI  - Importance of placebo effect in cough clinical trials.
AB  - Cough is a unique symptom because, unlike sneeze and other symptoms, it can be
      under voluntary control and this complicates clinical trials on cough medicines.
      All over-the-counter cough medicines (OTC) are very effective treatments because
      of their placebo effect. The placebo effect is enhanced by expectancy related to
      advertising, brand, packaging, and formulation. This placebo effect creates a
      problem for the conduct of clinical trials on OTC cough medicines that attempt to
      demonstrate the efficacy of a pharmacological agent above that of any placebo
      effect. Up to 85% of the efficacy of some cough medicines can be attributed to a
      placebo effect. The placebo effect apparent in clinical trials consists of
      several components: natural recovery, regression of cough response toward mean,
      demulcent effect, effect of sweetness, voluntary control, and effects related to
      expectancy and meaning of the treatment. The placebo effect has been studied most
      in the pain model, and placebo analgesia is reported to depend on the activation
      of endogenous opioid systems in the brain; this model may be applicable to cough.
      A balanced placebo design may help to control for the placebo effect, but this
      trial design may not be acceptable due to deception of patients. The placebo
      effect in clinical trials may be controlled by use of a crossover design, where
      feasible, and the changes in the magnitude of the placebo effect in this study
      design are discussed.

PMID- 19760297
TI  - Comparison of site-specific bone mass indices in South African children of
      different ethnic groups.
AB  - This study reports on ethnic differences in bone mass before and after adjusting
      for differences in body size and bone area (BA). Lumbar spine (LSBMC), proximal
      femur (PFBMC) and femoral neck (FNBMC) bone mineral contents were measured in
      black ('black'; n = 263) and white ('white'; n = 73) children from Johannesburg
      and children of mixed ancestral origin ('mixed'; n = 64) from Cape Town, South
      Africa. Geometric estimates and the power coefficient from the regression
      analyses of BMC on BA were calculated. After adjusting for age, weight, and
      height, LSBMC in girls and FNBMC in girls and boys were greatest in mixed,
      followed by black and then white, groups. Mixed boys and girls also had greater
      PFBMC than their black and white peers, but only in the boys was PFBMC greater in
      the black than the white groups. When including BA in the adjustment, differences
      remained at the FN in boys and girls, and the LS and PF in girls, but disappeared
      at the PF in mixed and black boys. The difference in LSBMC between mixed and
      black boys became significant after adjustment for age, weight, height, and BA.
      Geometric estimates at the femoral neck were greater in the mixed group. Power
      coefficients were greater in the white group, suggesting differences in shape or
      bone distribution. In conclusion, this study suggests that, in addition to
      differences in BMC, differences in bone strength and geometry are present which
      might confer advantages to the bone of mixed-ancestry children.

PMID- 19760298
TI  - Effect of physical activity on calcium homeostasis and calciotropic hormones: a
      review.
AB  - Physical exercise has frequently been shown to improve bone mass, especially at
      load-bearing bone sites. It is widely acknowledged that the anabolic effects of
      exercise on bone tissue are related to the application of mechanical constraints,
      but part of the osteogenic response may be due to other factors. In particular,
      various hormonal parameters that are modified by training, such as insulin-like
      growth factor-1 and sexual hormones, may modulate the bone response. In contrast,
      little is known about the involvement of calciotropic hormones in the adaptation
      mechanism of bone tissue. These hormones, which include parathyroid hormone,
      vitamin D metabolites, and calcitonin, are highly implicated in the regulation of
      both bone remodeling and calcium homeostasis. In addition to their direct action
      on bone cell activity, these hormones act on various target tissues such as
      kidney and intestine. This article describes the acute and long-term effects of
      exercise on both calcium homeostasis and calciotropic hormones in various
      populations. It clearly shows that exercise modifies calcium homeostasis and
      calciotropic hormone levels and that the variations in response are modulated by
      parameters related to exercise, including duration and intensity, as well as by
      individual characteristics such as age, sex, and training status.

PMID- 19760299
TI  - Developing predictive models of health literacy.
AB  - INTRODUCTION: Low health literacy (LHL) remains a formidable barrier to improving
      health care quality and outcomes. Given the lack of precision of single
      demographic characteristics to predict health literacy, and the administrative
      burden and inability of existing health literacy measures to estimate health
      literacy at a population level, LHL is largely unaddressed in public health and
      clinical practice. To help overcome these limitations, we developed two models to
      estimate health literacy. METHODS: We analyzed data from the 2003 National
      Assessment of Adult Literacy (NAAL), using linear regression to predict mean
      health literacy scores and probit regression to predict the probability of an
      individual having 'above basic' proficiency. Predictors included gender, age,
      race/ethnicity, educational attainment, poverty status, marital status, language
      spoken in the home, metropolitan statistical area (MSA) and length of time in
      U.S. RESULTS: All variables except MSA were statistically significant, with lower
      educational attainment being the strongest predictor. Our linear regression model
      and the probit model accounted for about 30% and 21% of the variance in health
      literacy scores, respectively, nearly twice as much as the variance accounted for
      by either education or poverty alone. CONCLUSIONS: Multivariable models permit a
      more accurate estimation of health literacy than single predictors. Further, such
      models can be applied to readily available administrative or census data to
      produce estimates of average health literacy and identify communities that would
      benefit most from appropriate, targeted interventions in the clinical setting to
      address poor quality care and outcomes related to LHL.

PMID- 19760300
TI  - Sympathetic and parasympathetic regulation of rectal motility in rats.
AB  - INTRODUCTION: The colon and rectum are regulated by the autonomic nervous system
      (ANS). Abnormalities of the ANS are associated with diseases of the colon and
      rectum while its modulation is a putative mechanism for sacral nerve stimulation.
      The purpose of this study is to establish a rat model elucidating the role of the
      efferent ANS on rectal motility. MATERIALS AND METHODS: Rectal motility following
      transection or stimulation of parasympathetic pelvic nerves (PN) or sympathetic
      hypogastric nerves (HGN) was measured with rectal strain gauge transducers and
      quantified as a motility index (MI). Colonic transit was measured 24 hours after
      transection by calculating the geometric center (GC) of distribution of (51)Cr
      RESULTS AND DISCUSSION: Transection of PN and HGN decreased MI to 518 +/- 185 g*s
      (p < 0.05) and increased MI to 5,029 +/- 1,954 g*s (p < 0.05), respectively,
      compared to sham (975 +/- 243 g*s). Sectioning of PN and HGN decreased transit
      with GC = 4.9 +/- 0.2 (p < 0.05) and increased transit with GC = 8.1 +/- 0.7 (p <
      0.02), respectively, compared to sham (GC = 5.8 +/- 0.3). Stimulation of PN and
      HGN increased MI to 831 +/- 157% (p < 0.01) and decreased MI to 251 +/- 24% (p <
      0.05), respectively. CONCLUSION: Rectal motility is significantly altered by
      sectioning or stimulating either HGN or PN. This model may be useful in studying
      how sacral nerve stimulation exerts its effects and provide insight into the
      maladies of colonic motility.

PMID- 19760301
TI  - Predicting organ space surgical site infection with a nomogram.
AB  - PURPOSE: We hypothesized that organ space surgical site infections (organ space
      SSI) are a unique type of surgical site infection and therefore are associated
      with a unique set of risk factors. The aim of this study was to create a
      predictive model for organ space SSI after small bowel, colon, or rectal
      operations. METHODS: The 2006 American College of Surgeons-National Surgical
      Quality Improvement Program (ACS-NSQIP) sample (N = 12,373) was used to identify
      current procedural terminology codes for small bowel, colon, and rectal
      laparoscopic or open surgical procedures. The following variables were used to
      build a predictive model of organ space SSI within 30 days post-op: age, gender,
      body mass index, American Society of Anesthesiologists class, smoking, diabetes,
      steroid use, 30 days previous radiotherapy or surgery, preoperative serum
      creatinine and albumin, laparoscopic surgery, wound class, perioperative
      transfusion, operative time, and surgical site. Patients on chronic mechanical
      ventilation, dialysis, wound infection, or sepsis preoperatively were excluded.
      RESULTS: Our organ space SSI model achieved a concordance index of 0.65 when
      validated in 2007 ACS-NSQIP patients (N = 9,521). A risk calculator designed
      based upon our model is available at www.clinicriskcalculators.com . CONCLUSION:
      This novel and validated nomogram is useful to predict organ space SSI associated
      with small bowel, colon, and rectal surgical procedures. It may also be useful
      for risk stratification and risk modification.

PMID- 19760302
TI  - The impact of socioeconomic status on presentation and treatment of diverticular
      disease.
AB  - INTRODUCTION: Diverticular disease is a common medical problem, but it is unknown
      if lower socioeconomic status (SES) affects patient outcomes in diverticular
      disease. MATERIAL AND METHODS: The New York (NY) State Inpatient Database was
      used to query 8,117 cases of diverticular disease occurring in patients aged 65
      85 in 2006. Race and SES were assessed by creating a composite score based on
      race, primary insurance payer, and median income bracket. RESULTS: Primary
      outcomes were differences in disease presentation, use of elective surgery,
      complication rates when surgery was performed, and overall mortality and length
      of stay. Patients of lower SES were younger, more likely to be female, to have
      multiple co-morbid conditions, to present as emergent/urgent admissions, and to
      present with diverticulitis complicated by hemorrhage (p < 0.0001). DISCUSSION:
      Overall, patients of low SES were less likely to receive surgical intervention,
      while rates of surgery were similar in elective cases. When surgery was
      performed, patients of lower SES had similar complication rates (25.4% vs. 20.2%,
      p = 0.06) and higher overall mortality (9.0% vs. 4.4%, p = 0.003). CONCLUSION:
      Patients of low SES who are admitted with diverticular disease have an increased
      likelihood to present emergently, have worse disease on admission, and are less
      likely to receive surgery.

PMID- 19760303
TI  - Evaluation and treatment of superficial esophageal cancer.
AB  - INTRODUCTION: Adenocarcinoma of the esophagus is the fastest increasing cancer in
      the USA, and an increasing number of patients are identified with early-stage
      disease. The evaluation and treatment of these superficial cancers differs from
      local and regionally advanced lesions. METHODS: This paper is a review of the
      current methods to diagnose, stage, and treat superficial esophageal
      adenocarcinoma. RESULTS: Intramucosal adenocarcinoma can be effectively treated
      with endoscopic resection techniques and with less morbid surgical options
      including a vagal-sparing esophagectomy. However, submucosal lesions are
      associated with a significant risk for lymph node metastases and are best treated
      with esophagectomy and lymphadenectomy. DISCUSSION: There has been a major shift
      in the treatment for Barrett's high-grade dysplasia and superficial esophageal
      adenocarcinoma in the past 10 years. New therapies minimize the morbidity and
      mortality of traditional forms of esophagectomy and in some cases allow
      esophageal preservation. Individualization of therapy will allow maximization of
      successful outcome and quality of life with minimization of complications and
      recurrence of Barrett's or cancer.

PMID- 19760304
TI  - The molecular pathogenesis of Barrett's esophagus: common signaling pathways in
      embryogenesis metaplasia and neoplasia.
AB  - Although Barrett's esophagus has been recognized for over 50 years, the cellular
      and molecular mechanisms leading to the replacement of squamous esophageal
      epithelium with a columnar type are largely unknown. Barrett's is known to be an
      acquired process secondary to chronic gastroesophageal reflux disease and occurs
      in the presence of severe disruption of the gastroesophageal barrier and reflux
      of a mixture of gastric and duodenal content. Current hypothesis suggest that
      epithelial change occurs due to stimulation of esophageal stem cells present in
      the basal layers of the epithelium or submucosal glands, toward a columnar
      epithelial differentiation pathway. The transcription factor CDX2 seems to play a
      key role in promoting the cellular biology necessary for columnar
      differentiation, and can be induced by bile salt and acid stimulation. Several
      cellular signaling pathways responsible for modulation of intestinal
      differentiation have also been identified and include WNT, Notch, BMP, Sonic HH
      and TGFB. These also have been shown to respond to stimulation by bile acids,
      acid or both and may influence CDX2 expression. Their relative activity within
      the stem cell population is almost certainly responsible for the development of
      the esophageal columnar epithelial phenotype we know as Barrett's esophagus.

PMID- 19760305
TI  - National trends in esophageal surgery--are outcomes as good as we believe?
AB  - INTRODUCTION: Positive volume-outcome relationships in esophagectomy have
      prompted support for regionalization of care; however, outcomes have not recently
      been analyzed. This study examines national trends in provision of esophagectomy
      and reassesses the volume-outcome relationship in light of changing practice
      patterns and training paradigms. METHODS: The Nationwide Inpatient Sample was
      queried from 1998 to 2006. Quantification of patients' comorbidities was made
      using the Charlson Index. Using logistic regression modeling, institutions'
      annual case volumes were correlated with risk-adjusted outcomes over time, as
      well as presence or absence of fellowship and residency training programs.
      RESULTS: A nationwide total of 57,676 esophagectomies were recorded. In-hospital
      unadjusted mortality fell from 12% to 7%. Adjusting for comorbidities, greater
      esophagectomy volume was associated with improvements in the incidence of most
      measured complications, though mortality increased once greater than 100 cases
      were performed. Hospitals supporting fellowship training or a surgical residency
      program did not have higher rates of mortality or total complications.
      CONCLUSIONS: The current national mortality rate of 7% following esophagectomy is
      higher than is reported in most contemporary case series. A greater annual
      esophagectomy volume improves outcomes, but only up to a point. Current training
      paradigms are safe.

PMID- 19760306
TI  - Impact of neoadjuvant chemotherapy with FOLFOX/FOLFIRI on disease-free and
      overall survival of patients with colorectal metastases.
AB  - STUDY AIMS: To determine if neoadjuvant FOLFOX/FOLFIRI is associated with
      improved disease-free survival (DFS) or overall survival (OS) in patients with
      colorectal metastases (CRM) to the liver. METHODS: Ninety-nine patients (from 457
      eligible) with CRM that underwent hepatic resection during 2000 to 2005 were
      included. Group 1 (n = 44) patients received neoadjuvant FOLFOX/FOLFIRI, and
      Group 2 (n = 55) did not receive neoadjuvant therapy. RESULTS: There were 58%
      men. The median age for Group 1 was 58 and Group 2, 64 (p = 0.03). OS for Group 1
      at 1, 3, and 5 years was 93%, 62%, and 51%, respectively, with a median OS of 5.8
      years. In Group 2 survival at 1l, 3, and 5 years was 90%, 63%, and 45%,
      respectively, with a median OS of 3.7 years (HR 1.06, p = 0.87). The DFS for
      Group 1 at 1, 3, and 5 years was 51%, 20%, and 20%, with a median DFS of 1.1
      years and Group 2 at 1, 3, and 5 years was 58%, 32%, and 32% (median DFS-1.2
      years; HR = 1.24, p = 0.45). CONCLUSIONS: Neoadjuvant FOLFOX/FOLFIRI was employed
      more frequently in younger patients with CRM; however, neoadjuvant chemotherapy
      for CRM was not significantly associated with an increase in OS or DFS, despite
      additional adjuvant therapy.

PMID- 19760307
TI  - Readmission after pancreatectomy for pancreatic cancer in Medicare patients.
AB  - OBJECTIVE: The objective of this study was to use a population-based dataset to
      evaluate the number of readmissions and reasons for readmission in Medicare
      patients undergoing pancreatectomy for pancreatic cancer. METHODS: We used
      Surveillance, Epidemiology, and End Results-Medicare linked data (1992-2003) to
      evaluate the initial hospitalization, readmission rates within 30 days (early),
      and between 30 days and 1 year (late) after initial discharge and reasons for
      readmission in patients 66 years and older undergoing pancreatectomy. RESULTS: We
      identified 1,730 subjects who underwent pancreatectomy for pancreatic cancer. The
      in-hospital mortality was 7.5%. The overall Kaplan-Meier readmission rate was 16%
      at 30 days and 53% at 1 year, accounting for 15,409 additional hospital days.
      Early readmissions were clearly related to operative complications in 80% of
      cases and unrelated diagnoses in 20% of cases. Late readmissions were related to
      recurrence in 48%, operative complications in 25%, and unrelated diagnoses in 27%
      of cases. In a multivariate analysis, only distal pancreatic resection (P = 0.02)
      and initial postoperative length of stay > or =10 days (P = 0.03) predicted early
      readmission. When compared to patients not readmitted, patients readmitted early
      had worse median survival (11.8 vs.16.5 months, P = 0.04), but the 5-year
      survival was identical (18%). Late readmission was associated with worse median
      and 5-year survival (19.4 vs. 12.1 months, 12% vs. 21%, P < 0.0001). CONCLUSIONS:
      Our study demonstrates overall 30-day and 1-year readmission rates of 16% and
      53%. The majority of early readmissions were related to postoperative
      complications but not related to patient and tumor characteristics. Complications
      causing early readmission are a cause of early mortality and are potentially
      preventable. Conversely, late readmissions are related to disease progression and
      are a marker of early mortality and not the cause.

PMID- 19760308
TI  - Margin positive pancreaticoduodenectomy is superior to palliative bypass in
      locally advanced pancreatic ductal adenocarcinoma.
AB  - BACKGROUND: Pancreatic ductal adenocarcinoma is an aggressive disease. Surgical
      resection with negative margins (R0) offers the only opportunity for cure.
      Patients who have advanced disease that limits the chance for R0 surgical
      resection may undergo margin positive (MP) pancreaticoduodenectomy (PD),
      palliative surgical bypass (PB), celiac plexus neurolysis alone (PX), or
      neoadjuvant chemoradiation therapy in anticipation of future resection.
      OBJECTIVE: The aim of this study was to determine if there is a difference in the
      perioperative outcomes and survival patterns between patients who undergo MP PD
      and those who undergo PB for locally advanced disease in the treatment of
      pancreatic ductal adenocarcinoma. METHODS: We reviewed our pancreatic surgery
      database (January 2005-December 2007) to identify all patients who underwent
      exploration with curative intent of pancreatic ductal adenocarcinoma of the
      head/neck/uncinate process of the pancreas. Four groups of patients were
      identified, R0 PD, MP PD, PB, and PX. RESULTS: We identified 126 patients who
      underwent PD, PB, or PX. Fifty-six patients underwent R0 PD, 37 patients
      underwent MP PD, 24 patients underwent a PB procedure, and nine patients
      underwent PX. In the PB group, 58% underwent gastrojejunostomy (GJ) plus
      hepaticojejunostomy (HJ), 38% underwent GJ alone, and 4% underwent HJ alone. Of
      these PB patients, 25% had locally advanced disease and 75% had metastatic
      disease. All nine patients in the PX group had metastatic disease. The mean age,
      gender distribution, and preoperative comorbidities were similar between the
      groups. For the MP PD group, the distribution of positive margins on permanent
      section was 57% retroperitoneal soft tissue, 19% with more than one positive
      margin, 11% pancreatic neck, and 8% bile duct. The perioperative complication
      rates for the respective groups were R0 36%, MP 49%, PB 33%, and PX 22%. The 30
      day perioperative mortality rate for the entire cohort was 2%, with all three of
      these deaths being in the R0 group. The median follow-up for the entire cohort
      was 14.4 months. Median survival for the respective groups was R0 27.2 months, MP
      15.6 months, PB 6.5 months, and PX 5.4 months. CONCLUSIONS: Margin positive
      pancreaticoduodenectomy in highly selected patients can be performed safely, with
      low perioperative morbidity and mortality. Further investigation to determine the
      role of adjuvant treatment and longer-term follow-up are required to assess the
      durability of survival outcomes for patients undergoing MP PD resection.

PMID- 19760309
TI  - Neoadjuvant chemoradiotherapy for esophageal cancer: a review of meta-analyses.
AB  - BACKGROUND: Most randomized controlled trials (RCTs) that have compared
      neoadjuvant chemoradiation followed by surgery with surgery alone for locally
      advanced esophageal cancer have shown no difference in survival between the two
      treatments. Meta-analyses on neoadjuvant chemoradiation in esophageal cancer,
      however, are discordant. METHODS: For the present study, published meta-analyses
      on neoadjuvant chemoradiation for esophageal cancer were identified from the
      PubMed database and critically appraised in order to make a judgment on the
      applicability of neoadjuvant chemoradiation in clinical practice and decision
      making. RESULTS: Two of the six meta-analyses examined did not show a significant
      survival benefit in patients with resectable esophageal cancer. Differences in
      the studies included and statistical methods applied might account for this.
      Moreover, there was heterogeneity between the RCTs included in the meta-analyses
      with regard to the patients included, tumor histology, and radiotherapy and
      chemotherapy regimes. Also, surgical technique was not uniform. No data on
      individual patients were available for most meta-analyses. The RCTs included in
      the meta-analyses were of inadequate sample size. All were started in the
      nineties, and hence methods for diagnosis, staging, treatment delivery, and
      outcome measurement reflect clinical practice during that decade. CONCLUSIONS:
      The current data on neoadjuvant chemoradiation for esophageal cancer strongly
      indicate the need for designing future high-quality trials that will contribute
      to a better understanding of the role of neoadjuvant treatment for resectable
      cancer of the esophagus and help to identify patient subgroups that would benefit
      most.

PMID- 19760310
TI  - Multi-factor investigation of early postoperative cardiac arrhythmia for elderly
      patients with esophageal or cardiac carcinoma.
AB  - BACKGROUND: The purpose of the present study was to analyze the risk multi
      factors of postoperative cardiac arrhythmia for elderly patients with esophageal
      or cardiac carcinoma. METHODS: A total of 756 operations for elderly patients
      (>65 years of age) with esophageal or cardiac carcinoma were performed in our
      department from January 1997 to December 2006. These included 197 cases (26.1%)
      of various types of cardiac arrhythmia after operation. Logistic regression was
      adopted to analyze the risk multi-factors of postoperative cardiac arrhythmia.
      RESULTS: It showed that complications of other diseases before operation,
      selection of operation method, duration of anesthesia and operation,
      postoperative pain, anoxia, hypovolemia, acid-alkali disequilibrium, and
      electrolyte imbalance might be the risk factors of postoperative cardiac
      arrhythmia in elderly patients with esophageal or cardiac carcinoma, whereas
      minimally invasive endoscopic operation might be a protective factor.
      CONCLUSIONS: In order to decrease the risk factors leading to postoperative
      cardiac arrhythmia for elderly patients with esophageal or cardiac carcinoma, it
      was necessary to completely evaluate the functions of heart and lung, improve the
      nutrition and metabolism of heart muscle, conduct effective breathing exercises,
      and correct the existing cardiac arrhythmia of such patients before operation,
      and perform the minimally invasive operation, shorten operation duration, relieve
      pain efficiently during the perioperative period, and correct hypovolemia and
      acid-alkali disequilibrium and electrolyte imbalance.

PMID- 19760311
TI  - Incidental gallbladder carcinoma diagnosed during or after laparoscopic
      cholecystectomy.
AB  - BACKGROUND: Gallbladder carcinoma (GC) is a highly lethal neoplasm. With the
      increase of cholecystectomies since the wide acceptance of laparoscopic
      cholecystectomy (LC), the incidental diagnosis of gallbladder carcinoma is more
      frequent. The aim of the present study was to report our experience with GC
      diagnosed during or after the performance of LC. METHODS: A total of 10,466 LCs
      were carried out from January 1999 to December 2007 in our hospital. Records of
      patients with incidental carcinoma were collected and analyzed retrospectively.
      RESULTS: Of all the patients, 20 (0.19%) were histopathologically diagnosed as
      having a GC. There were 4 men and 16 women; the median age in this group was 65.7
      years (range: 37-81 years).The depth of cancer invasion was: pTis (4 cases), pT1a
      (2 cases), pT1b (2 cases), pT2 (6 cases), pT3 (4 cases), and pT4 (2 cases). The
      sensitivity and specificity of intraoperatively frozen section examination were
      83.3 and 100%, respectively. Patients with in situ, pT1a and pT1b tumors
      underwent LC only, and there were no recurrences. The survival rate between
      patients with GC diagnosed during or after LC showed no difference; it was
      dependent on the depth of cancer invasion. CONCLUSIONS: The survival with
      incidental GC is related to stage, and it validates that a carefully performed LC
      is adequate treatment for carcinoma in situ, and stage 1a and b cancer. A frozen
      section examination was helpful but did not provide a definitive diagnosis.
      Meticulous techniques during LC, including retrieval of the gallbladder in a
      retrieval bag, may prevent port-site recurrence and intraperitoneal
      dissemination.

PMID- 19760313
TI  - Comparison of four staging systems of lymph node metastasis in gastric cancer.
AB  - BACKGROUND: The classification of lymph node metastasis in patients with gastric
      cancer is still controversial. Our aim was to evaluate the relative merits of
      four staging systems of lymph node metastasis. METHODS: In our study, the nodal
      status was classified according to the 5th edition of the tumor node metastasis
      (TNM) system, the Japanese Classification of Gastric Carcinoma (JCGC), the ratio
      of metastatic lymph nodes, and the size of the largest metastatic lymph node.
      Each staging system was scored as good (+2), fair (+1), or poor (0) with respect
      to the theoretical value (extent of the anatomical lymphatic tumor spread),
      convenience (simplicity), surgical applicability (extent of lymph node
      dissection), and prognostic value (ability to predict survival rate). RESULTS: In
      the multivariate analysis including the four staging systems and other potential
      prognostic factors, stepwise Cox regression revealed that the ratio of metastatic
      lymph nodes was the most independent prognostic factor. The TNM, ratio, and size
      systems were convenient because they had no consideration for the location of the
      tumor and lymph node. Although the JCGC system had advantages in theoretical
      value and surgical application, it was most optional due to the complexity of the
      system. CONCLUSIONS: Although all different staging systems are comparable, the
      metastatic lymph node ratio system is convenient, reproducible, and has the
      highest ability to predict survival.

PMID- 19760314
TI  - Surgical classification of open abdomen: which clinical implications?

PMID- 19760312
TI  - Management of liver trauma.
AB  - BACKGROUND: Blunt and penetrating liver trauma is common and often presents major
      diagnostic and management problems. METHODS: A literature review was undertaken
      to determine the current consensus on investigation and management strategies.
      RESULTS: The liver is the most frequently injured organ following abdominal
      trauma. Immediate assessment with ultrasound has replaced diagnostic peritoneal
      lavage in the resuscitation room, but computerised tomography remains the gold
      standard investigation. Nonoperative management is preferred in stable patients
      but laparotomy is indicated in unstable patients. Damage control techniques such
      as perihepatic packing, hepatotomy plus direct suture, and resectional
      debridement are recommended. Major complex surgical procedures such as anatomical
      resection or atriocaval shunting are now thought to be redundant in the emergency
      setting. Packing is also recommended for the inexperienced surgeon to allow
      control and stabilisation prior to transfer to a tertiary centre. Interventional
      radiological techniques are becoming more widely used, particularly in patients
      who are being managed nonoperatively or have been stabilised by perihepatic
      packing. CONCLUSIONS: Management of liver injuries has evolved significantly
      throughout the last two decades. In the absence of other abdominal injuries,
      operative management can usually be avoided. Patients with more complex injuries
      or subsequent complications should be transferred to a specialist centre to
      optimise final outcome.

PMID- 19760315
TI  - Comparison of invasiveness between laparoscopy-assisted total gastrectomy and
      open total gastrectomy.
AB  - BACKGROUND: Because only a few studies have been performed to date on the
      invasiveness of laparoscopy-assisted total gastrectomy (LATG) compared with open
      total gastrectomy (OTG), the minimal invasiveness of LATG has been unclear.
      METHODS: The OTG cohort contained 35 cases, which were performed from April 2003
      to October 2005. The LATG cohort contained 46 cases, which were performed from
      November 2005 to November 2008. Postoperative changes over time in various
      parameters relating to minimal invasiveness were evaluated. We used the Wong
      Baker FACES Pain Rating Scale to evaluate pain. Vital signs and a face scale were
      analyzed using daily maximum values on postoperative days (POD) 1-7. A
      hematological examination was performed on the preoperative day and POD 1, 4, 7,
      and 10. The number of days until oxygen saturation level (SaO2) was 95% or more
      in room air was used to evaluate respiratory function. RESULTS: Significantly
      lower pain scores were obtained in the LATG group on POD 1, 4, 5, and 7. There
      was a significantly lower body temperature in the LATG group on POD 7. A
      significantly lower white blood cell count was revealed for LATG patients on POD
      10, and for C-reactive protein on POD 1. Significantly higher serum total protein
      values were observed in the LATG group on POD 1, 4, and 7. Significantly lower
      blood sugar level was found in the LATG group on POD 4 and 7. The number of days
      until SaO2 was 95% or more in room air was significantly fewer in the LATG group.
      CONCLUSIONS: LATG seems to be a less invasive procedure than OTG.

PMID- 19760316
TI  - The lymph node ratio is a powerful prognostic factor of node-positive colon
      cancers undergoing potentially curative surgery.
AB  - BACKGROUND: The number of harvested (LNs) and metastatic nodes (LNs+) represents
      the most significant factor to define postoperative treatment and prognosis in
      colon cancer. However, its assessment may be inadequate causing an incorrect
      cancer staging. The lymph node ratio (LNR: the ratio between metastatic and
      resected nodes) has shown prognostic significance in many tumors; however, its
      role in colon cancer is not clearly elucidated. This study investigated LNR as a
      prognostic factor in node-positive colon cancers. METHODS: A total of 145
      consecutive patients with node-positive colon cancer who underwent curative
      surgery and adjuvant chemotherapy in a single oncologic unit entered this study.
      RESULTS: LNR ranged from 0.0416 to 0.9; it was clearly lower in pN1 than pN2
      patients, and increased as tumor stage worsened. ROC analysis selected 0.1818 as
      the best LNR cutoff value. Low LNR patients did significantly better than high
      LNR patients; this difference was not dependent on the number of LNs and stronger
      than differences observed by grouping patients according to LNs or LNs+. When
      stratified by low and high LNR value, pN1 and pN2 patients, as well as stage III
      subgroups were shown to display substantially different outcomes. LNR was an
      independent prognostic factor for disease-specific survival, and the only
      covariate related to disease-free survival. CONCLUSIONS: LNR was a robust
      prognostic indicator for node-positive colon cancers undergoing curative surgery.
      Because this ratio-based staging was demonstrated to reduce stage migration and
      to aid in identifying high-risk patients, it should be proposed as a standard
      tool for colon cancer staging.

PMID- 19760317
TI  - A critical evaluation of risk factors for complications after cytoreductive
      surgery and perioperative intraperitoneal chemotherapy for colorectal peritoneal
      carcinomatosis.
AB  - BACKGROUND: Cytoreductive surgery (CRS) combined with perioperative
      intraperitoneal chemotherapy (PIC) has demonstrated improved survival in selected
      patients with colorectal peritoneal carcinomatosis (CRPC). This treatment
      modality is associated with relatively high rates of perioperative morbidity and
      mortality. This study evaluated the clinical and treatment-related risk factors
      for perioperative morbidity and mortality in patients with CRPC who underwent CRS
      and PIC. METHODS: Sixty-three consecutive patients who underwent CRS and PIC for
      CRPC were evaluated. Adverse events were rated from grades I to V with increasing
      severity. Clinical and treatment-related risk factors for grades III and IV/V
      morbidity were determined. RESULTS: There were no perioperative deaths (0%). The
      grades III and IV morbidity rates were 14 and 17%, respectively. A peritoneal
      cancer index >12 (p = 0.019), transfusion >4 units (p = 0.028), number of
      peritonectomy procedures >3 (p = 0.013), left upper quadrant peritonectomy
      procedure (p < 0.001), and number of primary colonic anastomosis >1 (p = 0.004)
      were associated with grade IV morbidity on univariate analysis. Only left upper
      quadrant procedure was associated with grade IV morbidity on multivariate
      analysis (p = 0.002). Only number of primary colonic anastomosis >1 (p = 0.037)
      was associated with grade III morbidity on univariate analysis. This also was
      associated with grade III morbidity on multivariate analysis (p = 0.028).
      CONCLUSIONS: CRS and PIC has an acceptable risk of perioperative morbidity in
      carefully selected patients with CRPC. Patients who require extensive surgery
      have the highest risk for a severe adverse event. Preoperative evaluation of
      patients is essential to improve perioperative outcome.

PMID- 19760318
TI  - Prognostic significance of the metastatic lymph node ratio in gastric cancer
      patients.
AB  - BACKGROUND: Lymph node metastasis is considered one of the most important
      prognostic factors in gastric cancer. However, the optimal system for accurate
      staging of lymph node metastasis for patients with gastric cancer remains
      controversial. This study was designed to investigate the prognostic significance
      of the metastatic lymph node ratio (MLR), which is calculated by dividing the
      number of metastatic lymph nodes by the total number of nodes harvested from
      patients with gastric cancer. METHODS: We retrospectively analyzed the clinical
      data of 186 consecutive patients diagnosed with gastric cancer who underwent
      curative gastrectomy at our hospital. The lymph node status was classified
      according to three systems:the International Union Against Cancer/American Joint
      Committee on Cancer (UICC/AJCC) system; the Japanese Gastric Cancer Association
      (JGCA) system; and an MLR-based system (MLR0: 0, MLR1: 0.01-0.19, MLR2: >or=0.2).
      The influence of the MLR on patient survival was determined using univariate
      Kaplan-Meier survival analysis, the generalized Wilcoxon test, and analysis with
      the multivariate Cox proportional hazards model. RESULTS: The 5-year survival
      rate of the patients with MLR0, MLR1, and MLR2 was 88.6%, 59.4%, and 13.4%,
      respectively. In addition to the MLR, the UICC/AJCC N category,JGCA n category,
      tumor stage (pT category), and tumor diameter significantly influenced the 5-year
      survival rate, as determined by univariate analysis. Multivariate analyses
      revealed that of the three factors used to stage lymph node involvement, MLR was
      the most significant prognostic factor. CONCLUSIONS: The MLR is an important and
      easy-to-assess prognostic factor that should be considered for staging lymph node
      metastasis in patients with gastric cancer.

PMID- 19760319
TI  - Intermittent pringle maneuver and hepatic function: perioperative monitoring by
      noninvasive ICG-clearance.
AB  - BACKGROUND: Intermittent Pringle maneuver or selective portal clamping often are
      used to control inflow during parenchymal liver transection. This study was
      designed to determinate whether these maneuvers are associated with adverse
      hepatic function. METHODS: Resection was performed without portal clamping in 17
      patients (group 1). Selective continuous portal clamping was performed in 11
      patients (group 2) and the remaining 33 patients (group 3) had intermittent
      nonselective portal clamping (occlusion of the main portal trunk). The centers'
      protocol for total portal occlusion is 15-min occlusion alternated with 5-min
      reperfusion in patients with normal liver parenchyma or 10 min alternated with 5
      min in patients with abnormal parenchyma. ICG elimination tests were conducted
      concurrently using a noninvasive monitor that tracks the plasma disappearance
      rate (PDR-ICG-%/min) and 15-min retention rate after administration (ICG-R15-%).
      RESULTS: There was no statistically difference between the three studied groups
      in terms of sequential changes of ICG-PDR (p < 0.625) or ICG-R15 (p < 0.398).
      CONCLUSIONS: Our study indicates that 15 min of intermittent Pringle maneuver or
      selective hemihepatic continuous portal clamping are safe methods of vascular
      control during liver resection, with no adverse effects on hepatocellular
      function.

PMID- 19760320
TI  - Imprinting and epigenetic changes in the early embryo.
AB  - Imprinted genes are epigenetically regulated so that only one allele is expressed
      in a parent-of-origin-dependent manner. Although they represent a small subset of
      the mammalian genome, imprinted genes are essential for normal development. The
      regulatory mechanisms underlying imprinting are complex and have been the subject
      of extensive investigation. DNA methylation is the best-established epigenetic
      mark that is critical for the allele-specific expression of imprinted genes. This
      mark must be correctly established in the germline, maintained throughout life,
      and erased and reestablished in the germline the next generation. These events
      coincide with the genome-wide epigenetic reprogramming that occurs during
      gametogenesis and early embryogenesis; therefore, the establishment and
      maintenance of DNA methylation must be tightly regulated. Studies on enzymes that
      participate in both de novo methylation and its maintenance (i.e., the DNMT
      family) have provided information on how methylation influences imprinting.
      However, many aspects of the regulation of DNA methylation are unknown, including
      how methylation complexes are targeted and the molecular mechanisms underlying
      DNA demethylation. In this review we focus on the epigenetic changes that occur
      in the germline and early embryo, with an emphasis on imprinting. We summarize
      recent findings on factors influencing DNA methylation establishment,
      maintenance, and erasure that have further elucidated the mechanisms of
      imprinting, while highlighting topics that require further investigation.

PMID- 19760322
TI  - Characterization of the dwg mutations: dwg and dwg(Bayer) are new mutant alleles
      of the Ggt1 gene.
AB  - The dwg and dwg (Bayer) are allelic mutations of the mouse that are characterized
      by dwarfism, cataracts, and coat color change in homozygotes. The Ggt1 gene
      encodes gamma-glutamyltransferase 1 (GGT1), an extracellular membrane-bound
      enzyme that is critical for glutathione homeostasis. Both the dwg locus and Ggt1
      gene are localized on mouse chromosome 10, and the phenotypes of GGT1-deficient
      mice with targeted disruption of the Ggt1 gene show remarkable similarities with
      those of dwg/dwg and dwg (Bayer)/dwg (Bayer) mice. This evidence led us to
      hypothesize that the Ggt1 gene is responsible for dwg and dwg (Bayer) mutations.
      In this study we characterized dwg mutations by investigating their association
      with the Ggt1 gene. Histological analysis revealed reduced numbers of
      proliferative and hypertrophic chondrocytes in the growth plate of dwg/dwg mice,
      which are characteristic abnormalities observed in GGT1-deficient mice. To
      identify the causative mutations of dwg mutations, we analyzed the Ggt1 gene in
      dwg/dwg and dwg (Bayer)/dwg (Bayer) mice. In dwg/dwg mice, 13 nucleotides on exon
      7 of the Ggt1 gene were deleted, resulting in the generation of aberrant
      transcripts due to disrupted pre-mRNA splicing. Furthermore, dwg (Bayer)/dwg
      (Bayer) mice had a 46.7-kb deletion containing complete coding sequences of Ggt1
      and AI646023 genes and the first exon of the Ggt5 gene, which is closely related
      to the Ggt1 gene as a member of the GGT gene family. These results indicate that
      both dwg and dwg (Bayer) have defective mutations of the Ggt1 gene. Thus, we
      concluded that mutations in the Ggt1 gene are responsible for the phenotypes of
      dwg/dwg and dwg (Bayer)/dwg (Bayer) mice.

PMID- 19760321
TI  - Chromatin mechanisms in genomic imprinting.
AB  - Mammalian imprinted genes are clustered in chromosomal domains. Their mono
      allelic, parent-of-origin-specific expression is regulated by imprinting control
      regions (ICRs), which are essential sequence elements marked by DNA methylation
      on one of the two parental alleles. These methylation "imprints" are established
      during gametogenesis and, after fertilization, are somatically maintained
      throughout development. Nonhistone proteins and histone modifications contribute
      to this epigenetic process. The way ICRs mediate imprinted gene expression
      differs between domains. At some domains, for instance, ICRs produce long
      noncoding RNAs that mediate chromatin silencing. Lysine methylation on histone H3
      is involved in this developmental process and is particularly important for
      imprinting in the placenta and brain. Together, the newly discovered chromatin
      mechanisms provide further clues for addressing imprinting-related pathologies in
      humans.

PMID- 19760323
TI  - Genetic loci that regulate healing and regeneration in LG/J and SM/J mice.
AB  - MRL mice display unusual healing properties. When MRL ear pinnae are hole
      punched, the holes close completely without scarring, with regrowth of cartilage
      and reappearance of both hair follicles and sebaceous glands. Studies using
      (MRL/lpr x C57BL/6)F(2) and backcross mice first showed that this phenomenon was
      genetically determined and that multiple loci contributed to this quantitative
      trait. The lpr mutation itself, however, was not one of them. In the present
      study we examined the genetic basis of healing in the Large (LG/J) mouse strain,
      a parent of the MRL mouse and a strain that shows the same healing phenotype.
      LG/J mice were crossed with Small (SM/J) mice and the F(2) population was scored
      for healing and their genotypes determined at more than 200 polymorphic markers.
      As we previously observed for MRL and (MRL x B6)F(2) mice, the wound-healing
      phenotype was sexually dimorphic, with female mice healing more quickly and more
      completely than male mice. We found quantitative trait loci (QTLs) on chromosomes
      (Chrs) 9, 10, 11, and 15. The heal QTLs on Chrs 11 and 15 were linked to
      differential healing primarily in male animals, whereas QTLs on Chrs 9 and 10
      were not sexually dimorphic. A comparison of loci identified in previous crosses
      with those in the present report using LG/J x SM/J showed that loci on Chrs 9,
      11, and 15 colocalized with those seen in previous MRL crosses, whereas the locus
      on Chr 10 was not seen before and is contributed by SM/J.

PMID- 19760324
TI  - A whole-genome scan for recurrent airway obstruction in Warmblood sport horses
      indicates two positional candidate regions.
AB  - Recurrent airway obstruction (RAO), or heaves, is a naturally occurring asthma
      like disease that is related to sensitisation and exposure to mouldy hay and has
      a familial basis with a complex mode of inheritance. A genome-wide scanning
      approach using two half-sibling families was taken in order to locate the
      chromosome regions that contribute to the inherited component of this condition
      in these families. Initially, a panel of 250 microsatellite markers, which were
      chosen as a well-spaced, polymorphic selection covering the 31 equine autosomes,
      was used to genotype the two half-sibling families, which comprised in total 239
      Warmblood horses. Subsequently, supplementary markers were added for a total of
      315 genotyped markers. Each half-sibling family is focused around a severely RAO
      affected stallion, and the phenotype of each individual was assessed for RAO and
      related signs, namely, breathing effort at rest, breathing effort at work,
      coughing, and nasal discharge, using an owner-based questionnaire. Analysis using
      a regression method for half-sibling family structures was performed using RAO
      and each of the composite clinical signs separately; two chromosome regions (on
      ECA13 and ECA15) showed a genome-wide significant association with RAO at P <
      0.05. An additional 11 chromosome regions showed a more modest association. This
      is the first publication that describes the mapping of genetic loci involved in
      RAO. Several candidate genes are located in these regions, a number of which are
      interleukins. These are important signalling molecules that are intricately
      involved in the control of the immune response and are therefore good positional
      candidates.

PMID- 19760325
TI  - A call for "Smart Surveillance": a lesson learned from H1N1.

PMID- 19760326
TI  - Author reply to the letter to the editor, Re: 'Laparoscopic and open reversal of
      Hartmann's procedure-a comparative retrospective analysis.' Surgical Endoscopy
      2008(23):496-502.

PMID- 19760327
TI  - Totally laparoscopic vs. laparoscopically assisted distal gastrectomy for gastric
      cancer.

PMID- 19760328
TI  - Is laparoscopic gastrectomy safe for western patients with gastric cancer with
      high body mass index?

PMID- 19760330
TI  - Recurrent acute biliary pancreatitis: the protective role of cholecystectomy and
      endoscopic sphincterotomy.

PMID- 19760329
TI  - Single-port cholecystectomy with the TransEnterix SPIDER: simple and safe.
AB  - INTRODUCTION: Single-port or single-incision cholecystectomy with current rigid
      laparoscopic devices is limited by in-line visualization, restricting the ability
      to approach the surgical site with proper angles and instrumentation. A single
      port access system with articulating arms and strong instrumentation should
      minimize these issues. The TransEnterix system may facilitate safe and
      straightforward single-port surgery. METHODS: The TransEnterix single-port
      surgery system was used in both survival and nonsurvival porcine laparoscopic
      cholecystectomies under animal use committee approval. Nonsurvival procedures
      compared four standard laparoscopic with four single-port cholecystectomies from
      a histologic perspective. Five single-port swine laparoscopic cholecystectomy
      procedures were completed in sterile conditions, and all animals survived for 1
      week postoperatively. Standard surgical clips were used for both cystic duct and
      artery ligation. At sacrifice, both gross and microscopic histology were obtained
      for assessment of surgical complications. RESULTS: All cholecystectomies were
      successfully completed with the TransEnterix single-port system. Operative time
      for the survival procedures averaged 39.4 (range 18-66) min. Histology of the
      acute specimens showed less inflammation at the single-port site compared with
      the trocar sites from the standard cholecystectomy. At sacrifice, no
      complications were identified. CONCLUSIONS: The TransEnterix system is safe and
      straightforward for completing single-port cholecystectomy in this limited
      porcine series. Port site inflammation is reduced compared with standard
      laparoscopic trocars.

PMID- 19760331
TI  - Pitfalls of diagnostic laparoscopy in abdominal tuberculosis.
AB  - BACKGROUND: Diagnostic laparoscopy currently is emerging as an important tool in
      the diagnostic armamentarium for abdominal tuberculosis (TB). However, the
      laparoscopic view may be deceiving even to the most experienced eyes, and it is
      not uncommon for TB to be diagnosed erroneously before the final histologic
      confirmation is received. METHODS: A retrospective review of 20 diagnostic
      laparoscopies was conducted. The cases erroneously diagnosed at laparoscopy were
      collected and analyzed. RESULTS: Five cases (20%) were identified. For two
      patients, the laparoscopic findings were thought to be those of carcinomatosis,
      but histology showed TB. For the other three patients, TB was suspected
      laparoscopically, but the final diagnoses were carcinomatosis, spontaneous
      bacterial peritonitis, and panniculitis. Two patients died: one due to delayed
      diagnosis and treatment of abdominal TB and the other due to carcinomatosis.
      CONCLUSION: For a percentage of patients, the laparoscopic features of abdominal
      TB at diagnostic laparoscopy may be mistaken for other pathologies. Caution
      should be exercised before disclosure of the provisional diagnosis to the patient
      based on laparoscopy alone without histologic confirmation.

PMID- 19760332
TI  - Laparoscopic appendectomy by residents: evaluating outcomes  and learning curve.
AB  - BACKGROUND: Laparoscopic appendectomy is being performed increasingly, worldwide.
      To the resident, it provides a valuable opportunity to master basic laparoscopic
      skills. Studies have shown that laparoscopic appendectomy performed by residents
      is safe. However, to date, there is no clear evidence for the minimum number of
      these operations required to achieving proficiency and safety. The aim of this
      study is to assess the outcome of laparoscopic appendectomies performed by
      surgical residents and to evaluate the effect of learning curve on patient
      outcome. METHODS: All patients undergoing laparoscopic appendectomies performed
      by six residents during the study period were reviewed. Data on patient
      demographics,clinical and histological diagnosis, and outcome variables including
      operative duration, conversion to open surgery, complications, and length of stay
      were analyzed. We evaluated the effect of the learning curve by dividing patients
      into two groups: a first group consisting of the initial 20 patients and a second
      group consisting of the next 20 patients operated upon independently by each
      resident. Variables were analyzed to determine any difference between the two
      groups. RESULTS: Three hundred six patients with the clinical diagnosis of acute
      appendicitis underwent laparoscopic appendectomy by residents. Mean operative
      time was 83.8 min. Of patients, 14.6% required conversion to open surgery. Mean
      length of hospitalization was 2.82 days. Operative duration and complication rate
      were significantly reduced with increasing experience of residents. The length of
      hospital stay and conversion rate to open surgery remained unchanged. CONCLUSION:
      Operative duration and complications can be reduced with increasing experience of
      a resident.

PMID- 19760335
TI  - Single-incision laparoscopically assisted colectomy using standard laparoscopic
      instrumentation.
AB  - BACKGROUND: A prospective case series of transumbilical single-incision
      laparoscopic colectomies using conventional laparoscopic trocars and instruments
      is described. METHODS: Seven selected patients with colonic neoplasm underwent
      transumbilical SIL colectomy between November 2008 and March 2009. Three trocars
      via a single small umbilical incision were used. The bowel was mobilized and the
      vessels ligated intracorporeally with an extracorporeal anastomosis. RESULTS:
      This series of seven patients (6 men and 1 woman) had no conversion to standard
      multiport laparoscopy or open surgery. Six of the patients had pathology in the
      right colon, and one had a carcinoma at the splenic flexure. The patients had an
      average age of 71 years (range, 63-83 years) and an average body mass index (BMI)
      of 24.3 kg/m(2) (range, 21-28 kg/m(2)). The average operating time was 89 min
      (range, 75-115 min). No significant blood loss or complications occurred. The
      average length of hospital stay was 5.4 days (range, 4-11 days). The average
      incision length was 3.1 cm (range, 2.5-4.5 cm). Histopathology showed adequate
      tumor excision margins and an average lymph node yield of 15 nodes (range, 7-26
      nodes). CONCLUSIONS: Single-incision laparoscopic surgery for colectomy is
      feasible. It can be performed without specialized instrumentation and at no extra
      cost. Further evaluation is required.

PMID- 19760336
TI  - Intramuscular granular cell tumor in the lower extremities.
AB  - Granular cell tumors are uncommon but typically histologically benign neoplasms
      that occasionally behave as malignant tumors. Differentiation of benign granular
      cell tumors from malignant counterparts with radiographic and/or histologic
      analysis is crucial for physicians. We retrospectively studied five cases of
      intramuscular granular cell tumors arising in the lower extremities. All tumors
      had been histologically diagnosed as benign and were resected with a wide
      surgical margin. The minimum followup was 1 year (mean, 45 months; range, 12-119
      months) after surgery. Four patients had no local recurrence or distant
      metastasis (at a minimum of 18 months followup), whereas one patient with lymph
      node metastasis had a recurrence and distant metastasis 3 months after surgery
      resulting in death. Intramuscular granular cell tumors can be diagnosed based on
      their characteristic MRI features, such as peripheral high intensity on T2
      weighed images, and histologic evaluation. The histologic criteria described by
      Fanburg-Smith et al. can differentiate malignant granular cell tumors from benign
      tumors. A wide resection seems suitable for most granular cell tumors in the
      extremities. LEVEL OF EVIDENCE: Level IV, diagnostic study. See the Guidelines
      for Authors for a complete description of evidence.

PMID- 19760337
TI  - A serial analysis of gene expression profile of the Alzheimer's disease Tg2576
      mouse model.
AB  - Serial analysis of gene expression (SAGE), a technique that allows for the
      simultaneous detection of expression levels of the entire genome without a priori
      knowledge of gene sequences, was used to examine the transcriptional expression
      pattern of the Tg2576 mouse model of Alzheimer's disease (AD). Pairwise
      comparison between the Tg2576 and nontransgenic SAGE libraries identified a
      number of differentially expressed genes in the Tg2576 SAGE library, some of
      which were not previously revealed by the microarray studies. Real-time PCR was
      used to validate a panel of genes selected from the SAGE analysis in the Tg2576
      mouse brain, as well as the hippocampus and temporal cortex of sporadic AD and
      normal age-matched controls. NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 5
      (NDUFA5) and FXYD domain-containing ion transport regulator 6 (FXYD6) were found
      to be significantly decreased in the Tg2576 mouse brain and AD hippocampus. PTEN
      induced putative kinase 1 (PINK1), phosphatidylethanolamine binding protein
      (PEBP), crystalline mu (CRYM), and neurogranin (NRGN) were significantly
      decreased in AD tissues. The gene ontologies represented in the Tg2576 data were
      statistically analyzed and demonstrated a significant under-representation of
      genes involved with G-protein-coupled receptor signaling and odorant binding,
      while genes significantly over-represented were focused on cellular communication
      and cellular physiological processes. The novel approach of profiling the Tg2576
      mouse brain using SAGE has identified different genes that could subsequently be
      examined for their potential as peripheral diagnostic and prognostic markers for
      Alzheimer's disease.

PMID- 19760339
TI  - Polychlorinated biphenyl congeners in the aquatic environment of the Mekong
      River, South of Vietnam.
AB  - Polychlorinated biphenyl compounds (PCBs) were analyzed in sediments and clams'
      soft tissues from sampling sites in the Mekong River delta from the border with
      Cambodia to the coast of South China Sea. Concentrations of 13 individual PCB
      congeners are reported. Median concentration of SigmaPCB congeners was 0.279 ng
      g(-1) dry weight (range 0.106-2.016 ng g(-1) dry weight) in sediments, and 5.20
      ng g(-1) dry weight (range 1.89-19.37 ng g(-1)) in clams. Distribution and
      bioaccumulation of PCBs in the delta are discussed. It is concluded that in the
      Mekong River delta PCB concentrations were generally lower than in other regions
      of Vietnam and their likely sources have been waste discharges from repair
      workshops and other facilities in the delta cities.

PMID- 19760338
TI  - The study of myocardial perfusion and coronary  anatomy imaging roles in CAD
      (SPARC): design,  rationale, and baseline patient characteristics of  a
      prospective, multicenter observational registry  comparing PET, SPECT, and CTA
      for resource  utilization and clinical outcomes.
AB  - OBJECTIVES: To design a multicenter study comparing the prognostic value and post
      test resource utilization of PET, CT Coronary Angiography (CTA), and SPECT in
      clinical practice. BACKGROUND: Although PET, CTA, and SPECT are widely used,
      their relative clinical- and cost-effectiveness are undefined. METHODS: The Study
      of Myocardial Perfusion and Coronary Anatomy Imaging Roles in CAD (SPARC) is a
      prospective, multicenter, observational registry that has enrolled 3019 patients
      undergoing clinically referred SPECT, PET, and CTA with the goal of comparing
      posttest resource utilization and comparative prognostic value. Resource
      utilization assessment will enroll intermediate-high likelihood patients without
      prior CAD, while prognostic assessment will include both these patients and
      patients with prior CAD. Secondary analyses include assessments of diagnostic
      accuracy, cost, and referral to revascularization. Sites recruited into at least
      two of the three imaging arms. Except for semi-quantitative interpretation, site
      protocols will be used for all imaging studies and images forwarded to an image
      repository. Follow-up for catheterization, revascularization, cardiac death,
      myocardial infarction, all-cause death and medication use changes will be
      performed at 90-day, 1, and 2 years. Standard statistical methods will be used to
      risk-adjust results within and between study arms. SPARC will have >85% power
      (two-sided test, alpha = 0.01) to detect a 5% catheterization rate difference at
      90 days between the three arms and >90% power to detect a 2% difference in
      cardiac death, or nonfatal MI within 2 years of the index test.

PMID- 19760341
TI  - Genotoxic effects of the insecticide cypermethrin on the root meristem cells of
      sunflowers (Helianthus annuus L.).
AB  - In this study, the genotoxic effects of the insecticide cypermethrin on the root
      meristem cells of sunflowers (Helianthus annuus L.) were investigated. The roots
      were treated with 10- 25- 50- and 100-ppm concentrations of cypermethrin for 6,
      12 and 24 h. The mitotic index and mitotic abnormalities were determined in both
      control and test groups. The cypermethrin showed a marked mitodepressive action
      on mitosis. The types of mitotic abnormalities included disturbed metaphase, c
      mitosis, stickiness, laggards and chromatid bridges. A pronounced toxic effect
      was observed at the 50-ppm concentration. Cypermethrin may have genotoxic effects
      on sunflowers.

PMID- 19760340
TI  - Impact of N,N-dimethylformamide from domestic effluents on river waters.
AB  - The impacts of N,N-dimethylformamide (DMF) from domestic effluents on rivers were
      evaluated. The hourly DMF concentrations in the inflows (0.21-0.52 mug/L in mean)
      and the outflows (0.18-0.62 mug/L in mean) of two sewage treatment plants did not
      show any characteristic variations, and DMF was not removed at both plants. The
      monthly variations of DMF in the outflows of four sewage treatment plants (0.16
      0.62 mug/L in mean) and three rivers (0.06-0.11 mug/L in mean) into which the
      outflows of the plants were discharged did not show any significant variations.
      The domestic DMF load per person was calculated to be 0.25 mg/d/person. The
      percent DMF loads of domestic effluents in the rivers were estimated to be below
      (8%-32%).

PMID- 19760342
TI  - Distribution of mercury pollution and its source in the soils and vegetables in
      Guilin area, China.
AB  - Soils and vegetables were sampled and analyzed from nine vegetable fields in
      Guilin area, China. The average mercury (Hg) concentrations varied from 0.099 to
      0.546 mg/kg in soils and from 0.046 to 0.132 mg/kg in plants. The distribution of
      Hg pollution in plants was correlated with that in soils. Generally, the Hg
      concentration in the plants decreased with the increasing distance between
      sampling sites and the city center. The Hg existed mostly in leaves of the
      plants, and then in their roots and stems, which suggested that the Hg in the
      atmosphere might be an important source of Hg in plants.

PMID- 19760343
TI  - Dissipation of profenofos, imidacloprid and penconazole in tomato fruits and
      products.
AB  - An experiment was conducted to evaluate the effects of some technological
      processes on the residual levels of profenofos, imidacloprid and penconazole in
      tomato fruits and products. According to their half-life (t (1/2)) values, tomato
      fruits can be safely harvested for human consumption or for processing purposes 3
      days after the spray time of imidacloprid and penconazole and 7 days after in the
      case of profenofos. Pesticide residues were greatly decreased in tomato juice
      under cold or hot break compared with that taken from unwashed tomato fruits. A
      sharp decline in profenofos level was noted after treatment by pectinex ultra SP
      L and benzyme M during tomato crushing.

PMID- 19760344
TI  - Organochlorine compounds in blue mussels, Mytilus edulis, and Pacific oysters,
      Crassostrea gigas, from seven sites in the Lower Saxonian Wadden Sea, Southern
      North Sea.
AB  - Blue mussels (Mytilus edulis) and Pacific oysters (Crassostrea gigas) collected
      at seven locations in the Lower Saxonian Wadden Sea in January and February 2007
      were analysed for organochlorine compounds. Contaminants were present in all
      samples, albeit with variable amounts and composition. The highest values were
      found in the Jade Bay. Congener PCB 153 was the contaminant which had the highest
      content of all organochlorines tested (475.75-937.39 ng/g lipid). DDT was
      detected in one sample only while DDD and DDE were found in all samples, the
      latter with contents up to 351.34 ng/g lipid. No clear differentiation could be
      made in terms of accumulation of organochlorines for M. edulis and C. gigas.
      Comparison with data from 2001 to 2006 showed an increase in 2007, which may be
      due to the different season the samples were taken.

PMID- 19760345
TI  - Recently published abstracts and reviews.

PMID- 19760346
TI  - Berlin questionnaire.

PMID- 19760347
TI  - Unsatisfactory outcomes in myasthenia gravis: influence by care providers.
AB  - Myasthenia gravis (MG) can be difficult to treat despite an available therapeutic
      armamentarium. Our aim was to analyze the factors leading to unsatisfactory
      outcome (UO). To this end we used the Myasthenia Gravis Foundation of America
      classification system. Forty one patients with autoimmune MG were followed
      prospectively from January 2003 to December 2007. Outcomes were assessed
      throughout follow-up and at a final visit. 'Unchanged', 'worse', 'exacerbation'
      and 'died of MG' post-intervention status were considered UOs. During follow-up,
      UO rates reached 54% and were related to undertreatment (41%), poor treatment
      compliance (23%), infections (23%), and adverse drug effects (13%). The UO rate
      at final study assessment was 20%. UO during follow-up was significantly (P =
      0.004) predictive of UOs at final assessment. When care was provided by
      neuromuscular (NM) specialists, patients had significantly better follow-up
      scores (P = 0.01). At final assessment UO rates were 7% and significantly better
      in patients treated by NM specialists, compared to other physicians where UO
      rates reached 27%. UO was a frequent finding occurring in more than half our
      patients during follow-up. Nearly two-thirds of the UOs could have been prevented
      by appropriate therapeutic adjustments and improved compliance. The differential
      UO rates at follow-up, their dependency on the degree to which the management was
      specialized and their correlation with final outcomes suggest that specialized MG
      care improves outcomes.

PMID- 19760348
TI  - Intrathecal levels of IL-6 in Alzheimer's disease.

PMID- 19760350
TI  - Abstracts of the 2nd European Conference on Schizophrenia Research: from research
      to practice. September 21-23, 2009. Berlin, Germany.

PMID- 19760349
TI  - Humoral anti-proteasomal autoimmunity in dilated cardiomyopathy.
AB  - Virus-induced chronic inflammation, autoimmune processes and impaired protein
      quality control may be involved in the pathogenesis of dilated cardiomyopathy
      (DCM). The ubiquitin-proteasome system is important in the modulation of
      inflammatory processes and the immune response. Proteasomes were identified as
      targets of a humoral autoimmune response in systemic inflammatory diseases, which
      provoked us to investigate anti-proteasomal immunity in DCM in detail: a total of
      90 DCM patients with impaired left-ventricular function (LVEF < or = 45%) were
      enrolled in this study. Autoimmune response to cardiac proteasomes was found to
      be enhanced in DCM patients, revealing the detection of predominantly alpha
      subunits of the 20S proteasome complex. Proteasome antibody (ProtAb) levels were
      found to be particularly enhanced at stages of advanced heart failure: moderately
      decreased LVEF and considerably increased NT-pro BNP levels were observed in DCM
      patients who tested positive for ProtAb (P < 0.05). A linear regression model
      suggested a link between the detection of cardiotropic viruses in endomyocardial
      biopsies and anti-proteasomal immunity (P < 0.01). Likewise, ProtAb levels were
      enhanced in a murine model of chronic enterovirus myocarditis. Our data also
      point to a potential interaction of ProtAb with the cell surface: ProtAb exerted
      negative inotropic effects in field-stimulated cardiomyocytes. In conclusion,
      humoral autoreactive anti-proteasome immune responses appear to be enhanced in
      DCM. Viral infection of the myocardium may be linked to the induction of anti
      proteasomal immunity in DCM.

PMID- 19760352
TI  - A series of novel rare Earth molybdotungstosilicate heteropolyoxometalates
      binding to bovine serum albumin: spectroscopic approach.
AB  - Heteropolyoxometalate complexes have been widely applied in many fields. In this
      paper, the interaction between a series of novel rare earth
      molybdotungstosilicate heteropolyoxometalates,
      K(10)H(3)[Ln(SiMo(6)W(5)O(39))(2)].xH(2)O (abbr. LnW(5), Ln = Pr (x = 30), Gd (x
      = 29), Dy (x = 28), and Yb (x = 31)), and bovine serum albumin (BSA) was
      investigated by spectroscopic approach under the physiological conditions. In the
      mechanism discussion, it was proved that the fluorescence quenching of BSA by
      LnW(5) is a result of the formation of LnW(5)-BSA complex. Fluorescence quenching
      constants were determined using the Stern-Volmer equation to provide a measure of
      the binding affinity between LnW(5) and BSA. The binding affinity ranked in the
      order GdW(5) > DyW(5) > PrW(5) > YbW(5). The results of thermodynamic parameters
      DeltaG, DeltaH, and DeltaS at different temperatures indicate that van der Waals
      interactions and hydrogen bonds play a major role for LnW(5)-BSA association.
      Furthermore, the distance r between donor (BSA) and acceptor (LnW(5)) was
      obtained according to fluorescence resonance energy transfer.

PMID- 19760353
TI  - Determination of polychlorinated biphenyl congeners in water and sediment in
      North West Persian Gulf, Iran.
AB  - Polychlorinated biphenyl (PCB) was detected as isomer groups (congener numbers
      28, 52, 101, 118, 138, 153 and 180) in the coastal water and sediment of four
      stations around Shadegan wetland protected area in the northwestern part of the
      Persian Gulf. Total PCB concentration range was 8-375 ng/L in water and 3.4-50.2
      MUg/g in sediment. Concentration of different congeners and chromatogram
      indicates that the source of PCB in this area can be Clophen A60; it used for
      long time in Iranian electronic industries. Other chlorinated hydrocarbons such
      as lindane, DDT and their metabolites were also present in the samples.

PMID- 19760354
TI  - Polybrominated diphenyl ethers in the atmosphere of Taizhou, a major e-waste
      dismantling area in China.
AB  - Concentrations, congener profiles, gas-particle partitioning and size
      distributions of polybrominated diphenyl ethers (PBDEs) in the atmosphere of
      Taizhou were studied to evaluate the impact of e-waste recycling on the
      environment. Total concentration of 13 PBDEs near the e-waste dismantling area
      was 506 pg m(-3) in summer and 1,662 pg m(-3) in winter, about 7 times higher
      than that of the reference urban site, but much lower than that of Guiyu, another
      major e-waste dismantling area in China. This should be attributable to the
      centralized management measures taken in recent years in Taizhou. BDE-209 was the
      major congener and mainly in coarse particles.

PMID- 19760355
TI  - Long-term lower urinary tract dysfunction after radical hysterectomy in patients
      with early postoperative voiding dysfunction.
AB  - INTRODUCTION AND HYPOTHESIS: To compare long-term lower urinary tract dysfunction
      after radical hysterectomy in patients with or without early postoperative
      voiding dysfunction. METHODS: Thirty patients at least 2 years after radical
      hysterectomy were evaluated with multichannel urodynamic studies. Fifteen
      patients (group A) had early postoperative voiding dysfunction (required urethral
      catheterization more than 1 month), and 15 patients (group B) had no early
      postoperative voiding dysfunction. RESULTS: Overall voiding dysfunction was more
      prevalent in group A than group B (73.3% versus 33.3%, p > 0.05). In particular,
      high postvoid residual urine and abdominal straining increased significantly in
      group A (40% versus 0% and 60% versus 13.3%, respectively). Total and all domains
      scores from Urogenital Distress Inventory and Incontinence Impact Questionnaire
      were not different between both groups. CONCLUSION: High postvoid residual urine
      and abdominal straining increased significantly in patients with early
      postoperative voiding dysfunction without impairment on quality of life.

PMID- 19760356
TI  - Incidence, morphology and morphometry of the foramen of Vesalius: complementary
      study for a safer planning and execution of the trigeminal rhizotomy technique.
AB  - BACKGROUND: The foramen of Vesalius (FV) is located in the greater wing of the
      sphenoid bone between the foramen ovale (FO) and the foramen rotundum in an
      intracranial view. The FO allows the passage of the mandibular branch of
      trigeminal nerve, which is the target of the trigeminal radiofrequency rhizotomy.
      OBJECTIVE: We analyzed its location, morphology, morphometry and interrelation
      among other foramina. MATERIALS AND METHODS: 400 macerated adult human skulls
      were examined. A digital microscope (Dino-Lite plus) was used to capture images
      from the FV. A digital caliper was used to perform the measurements of the
      distance between the FV and other foramina (FO, foramen spinosum and the carotid
      canal) in an extracranial view of the skull base. RESULTS: In the 400 analyzed
      skulls, the FV was identified in 135 skulls (33.75%) and absent on both sides in
      265 skulls (66.25%). The FV was observed present bilaterally in 15.5% of the
      skulls. The incidence of unilateral foramen was 18.25% of the skulls of which
      7.75% on right side and 10.5% on left side. The diameter of the FV was measured
      and we found an average value of 0.65 mm, on right side 0.63 mm and on the left
      side 0.67 mm. We verified that positive correlations were statistically
      significant among the three analyzed distances. CONCLUSIONS: This study intends
      to offer specific anatomical data with morphological patterns (macroscopic and
      mesoscopic) to increase the understanding of the FV features as frequency,
      incidence and important distances among adjacent foramina.

PMID- 19760357
TI  - [Development of a new screening instrument for geriatric depression. The
      depression in old age scale (DIA-S)].
AB  - PURPOSE: The purpose of the study was to develop and validate the depression in
      old age scale (DIA-S). The DIA-S is a new screening scale for depression, which
      is comparable to the GDS-15 in terms of practicality but which is more
      appropriate for the use in geriatric patients. METHODS: The DIA-S and the GDS-15
      were validated among a sample of n=331 geriatric inpatients (n=151 depressed
      subjects and n=180 not depressed subjects), using the Montgomery and Asperg
      Depression Rating Scale as gold standard criterion for depression. For the
      comparison of the two scales, item analysis (missing values, difficulty,
      discriminatory power) was considered as well as test performance (internal
      consistency, correlation with the MADRS, ROC curves, sensitivity, specificity).
      RESULTS: All outcomes indicate a good psychometrical quality of the DIA-S. The
      new instrument showed a considerably higher discriminatory power for the items
      internal consistency and test specificity than the GDS-15.

PMID- 19760358
TI  - [Postural deficits and risk of falling in elderly persons with incipient
      osteoporosis].
AB  - BACKGROUND: Falls and fall-dependent complications represent major problems in
      geriatrics. Approximately 80-90% of femoral neck fractures in postmenopausal
      women are caused by falls. STUDY QUESTION: The goal of this study was to evaluate
      a new posturographic measurement system (Interactive Balance System, IBS)
      regarding its potential to predict falls in osteoporotic patients. MATERIALS AND
      METHODS: A total of 228 patients admitted for osteodensitometry because of
      suspected osteoporosis were included in the study. During the baseline
      investigation, bone density and postural regulation were measured. Over a follow
      up period of 12 months, all falls were recorded in a fall diary. Participants
      with more than two falls per year were classified as persons at high risk of
      falling. RESULTS: In patients with confirmed osteoporosis (n=139), the
      posturographic frequency range F(2-4) was found to be predictive for falls. The
      ROC analysis of the dependent fall index FIOR(F2-4) showed an AUC value of 0.88.
      CONCLUSION: IBS is an effective assessment for fall prediction in osteoporosis.
      Especially peripheral-vestibular regulation mechanisms seem to be of great
      importance in the evaluated patient group.

PMID- 19760360
TI  - Liver transplantation for hepatocellular carcinoma in the world: the Taiwan
      experience.
AB  - Liver transplantation (LT) has been regarded as "potentially curative" in a
      cirrhotic patient with hepatocellular carcinoma (HCC) because it removes the
      cancer and eradicates the cirrhosis. In Taiwan, HCC ranks first among the leading
      causes of cancer mortality in males and 4th in females. The most common causes
      are chronic hepatitis B virus-related cirrhosis, hepatitis C virus-related
      cirrhosis, and combined hepatitis B and C virus-related cirrhosis. The aggregate
      lifetime cost of hepatitis and HCC constitutes a significant burden on the
      Taiwanese health-care system. The reported overall (living-donor LT and deceased
      donor LT) 1- and 3-year survival rates for HCC after LT in Taiwan ranged from 86
      to 98% and 61 to 96%, respectively. Microscopic vascular invasion did not
      influence the outcome of patients, but high alpha-fetoprotein levels >200 ng/ml
      may be a risk factor for HCC recurrence after transplant.

PMID- 19760359
TI  - Predictors of adherence to a Mediterranean-type diet in the PREDIMED trial.
AB  - BACKGROUND: Determinants of dietary changes obtained with a nutritional
      intervention promoting the Mediterranean diet have been rarely evaluated. AIM: To
      identify predictors of higher success of an intervention aimed to increase
      adherence to a Mediterranean diet (MeDiet) in individuals at high cardiovascular
      risk participating in a trial for primary prevention of cardiovascular disease:
      the PREDIMED (PREvencion con DIeta MEDiterranea) trial. Candidate predictors
      included demographic and socioeconomic characteristics, cardiovascular risk
      factors, and baseline dietary habits. METHODS: A total of 1,048 asymptomatic
      subjects aged 55-80 years allocated to the active intervention groups (subjects
      in the control group were excluded). Participants' characteristics were assessed
      at baseline among subjects. Dietary changes were evaluated after 12 months. Main
      outcome measures were: attained changes in five dietary goals: increases in (1)
      fruit consumption, (2) vegetable consumption, (3) monounsaturated fatty acid
      (MUFA)/saturated fatty acid (SFA) ratio, and decreases in (4) sweets and pastries
      consumption, (5) and meat consumption. Univariate and multivariate logistic
      regression analyses were used to examine associations between the candidate
      predictors and likelihood of attaining optimum dietary change (improved adherence
      to a MeDiet). RESULTS: Among men, positive changes toward better compliance with
      the MeDiet were more frequent among non-diabetics, and among those with worse
      dietary habits at baseline (higher consumption of meat, higher SFA intake, lower
      consumption of fruit and vegetables). Among women, marital status (married) and
      worse baseline dietary habits (high in meats, low in fruits and vegetables) were
      the strongest predictors of success in improving adherence to the MeDiet.
      CONCLUSIONS: Some participant characteristics (marital status and baseline
      dietary habits) could contribute to predicting the likelihood of achieving
      dietary goals in interventions aimed to improve adherence to a MeDiet, and may be
      useful for promoting individualized long-term dietary changes and improving the
      effectiveness of dietary counseling.

PMID- 19760361
TI  - Liver transplantation for hepatocellular carcinoma: current topics in France.
AB  - BACKGROUND: Excellent survival obtained with liver transplantation (LT) for
      limited hepatocellular carcinoma (HCC) in patients with chronic liver disease is
      still challenged by the increasing discrepancy between candidates and grafts
      available. We review the current strategy of LT for HCC in our country
      highlighting the tendency: (1) to expand recipient selection beyond the Milan
      criteria, (2) to use systematic pre-LT treatments with a greater number of
      resections and (3) new rules for graft attribution. RESULTS: Although the vast
      majority of cirrhotic patients with HCC are transplanted within the Milan
      criteria; the number of candidates is continually rising, while the number of
      grafts available is stable with a disappearance of adult LDLTs. Moreover, the new
      rules for organ allocations, mainly based on the MELD score, minimize the
      accessibility to liver grafts for patients with HCC and compensated liver
      disease. For these reasons, in France we have observed an increase in waiting
      time for HCC patients, leading to the extensive use of pre-LT treatments in order
      to limit the list dropouts. Many studies have been performed on transarterial
      chemo-embolization (TACE) and supraselective TACE. Moreover, the use of liver
      resection (LR) as a bridge therapy, showing that initial resection does not
      impair short- and long-term survival, led French surgeons to develop the concept
      of LR as a way to select patients who might benefit from LT and to use it, in
      selected cases, as a primary therapy, considering LT as salvage treatment in case
      of recurrence. CONCLUSIONS: The number of HCC candidates who cannot benefit from
      a LT is increasing worldwide. The French answer to this situation involves pre-LT
      treatments, particularly partial LR, based mainly on the excellent Japanese
      results in this field. Moreover, the country of egalite is actually modifying the
      rules of graft attribution in order to reduce the inequality between the HCC
      patients with poor and good liver function.

PMID- 19760362
TI  - Analysis of the VP19 and VP28 genes of white spot syndrome virus in Korea and
      comparison with strains from other countries.
AB  - The results of our DNA analysis showed that there was 100% homology of the VP28
      and VP19 genes of white spot syndrome virus (WSSV) among the samples collected
      from different shrimp farms in Korea. Comparing with an earlier isolated Korean
      strain, Korea01, the genes nucleotide sequences had only a single base difference
      which was observed in both VP19 and VP28. This resulted in a single amino acid
      substitution at position 40 of the latter. This implies that a single genetic
      strain of WSSV has been circulating in Korea and that its mutation rate is very
      low. In comparison with known sequences of VP19 and VP28 genes of WSSV isolates
      from other countries, the Korean strains had more than 99% sequence homology with
      those in gene and protein. Based on our sequence analysis of VP19 and VP28 of
      WSSV from various shrimp farms in Korea, the WSSV strains circulating in the
      region were genetically identical and similar to the strain identified two years
      ago. In addition, the Korean strain had close genetic identity with strains
      circulating in other Asian countries as well as other continents.

PMID- 19760363
TI  - New insights into mineralogenic effects of vanadate.

PMID- 19760364
TI  - Phase I clinical and pharmacokinetic study of sorafenib in combination with
      carboplatin and paclitaxel in patients with advanced non-small cell lung cancer.
AB  - OBJECTIVES: Unsatisfactory efficacy of current treatments for advanced lung
      cancer has prompted the search for new therapies, with sorafenib, a multikinase
      inhibitor, being one candidate drug. This phase I trial was conducted to evaluate
      drug safety and pharmacokinetics as well as tumor response of sorafenib in
      combination with paclitaxel and carboplatin in patients with advanced non-small
      cell lung cancer (NSCLC). METHODS: Eligible patients received paclitaxel (200
      mg/m(2)) and carboplatin (area under the curve [AUC]of 6 mg min mL(-1)) on day 1
      and sorafenib (400 mg, twice daily) on days 2 through 19 of a 21-day cycle.
      RESULTS: Four of the initial six patients (cohort 1) experienced dose-limiting
      toxicities (DLTs), resulting in amendment of the treatment protocol. An
      additional seven patients (cohort 2) were enrolled, two of whom developed DLTs.
      DLTs included erythema multiforme, hand-foot skin reaction, and elevated plasma
      alanine aminotransferase in cohort 1 as well as gastrointestinal perforation at a
      site of metastasis and pneumonia in cohort 2. Most adverse events were
      manageable. One complete and six partial responses were observed among the 12
      evaluable patients. Coadministration of the three drugs had no impact on their
      respective pharmacokinetics. CONCLUSION: The present study confirmed that
      sorafenib at 400 mg once daily in combination with carboplatin AUC 5 mg min mL(
      1) and paclitaxel 200 mg/m(2) is feasible in Japanese patients with advanced
      NSCLC. The results of this study also showed that this combination therapy had
      encouraging antitumor activity and was not associated with relevant
      pharmacokinetic interaction in Japanese NSCLC patients.

PMID- 19760365
TI  - Factual understanding of randomized clinical trials: a multicenter case-control
      study in cancer patients.
AB  - Objective Several reports have shown that despite the informed consent process,
      enrolled patients misunderstand the modalities and goals of randomized clinical
      trials (RCTs). We believe that this may be linked to a priori misconceptions in
      the main population. The purpose of this study is to compare the knowledge about
      cancer RCTs in enrolled participants (cases) versus patients treated under cancer
      standard care who have never taken part in RCTs (controls). Methods We submitted
      a validated questionnaire (ICEC-R) to both populations to explore their knowledge
      about RCTs. A total of 75 cases and 107 controls were included. Results Globally,
      the cases' knowledge was significantly better, especially about (i) the
      randomization process, (ii) the uncertain potential benefits, and (iii) the right
      to withdraw consent. Both populations presented the lowest scores for items
      exploring the randomization process and uncertain treatment benefits. Conclusion
      Enrolled patients' comprehension of the goals and means of RCTs is actually
      better than controls'. Nevertheless, additional efforts should be made to enhance
      information about clinical research to patients as well as to the main
      population. Practice Implications Having better knowledge about patients'
      difficulties in understanding RCTs would allow physicians to adjust the
      information they give and then to enhance patients' well-being.

PMID- 19760366
TI  - Concomitant treatment of F98 glioma cells with new liposomal platinum compounds
      and ionizing radiation.
AB  - Despite significant advances, the radiotherapy and chemotherapy protocols
      marginally improve the overall survival of patients with glioblastoma.
      Lipoplatin(TM), and Lipoxal(TM), the liposomal formulations of cisplatin and
      oxaliplatin respectively, were tested on the F98 glioma cells for their ability
      to improve the cell uptake and increase the synergic effect when combined with
      ionizing radiation. The cytotoxicity and synergic effect of platinum compounds
      were assessed by colony formation assay, while the cellular uptake was measured
      by Inductively Coupled Plasma Mass Spectrometer (ICP-MS). After 4 h exposure with
      platinum compounds, cells were irradiated (1.5-6.6 Gy) with a (60)Co source. The
      liposomal formulations were compared to their liposome-free analogs and to
      carboplatin. The concomitant treatment of F98 cells with carboplatin and
      radiation produced the highest radiosensitizing effect (30-fold increase). Among
      the platinum compounds tested, Lipoplatin(TM) produced the most promising
      results. This liposomal formulation of cisplatin improved the cell uptake by 3
      fold, and its radiosensitizing potential was enhanced by 14-fold. Although
      Lipoxal(TM) can potentially reduce the adverse effect of oxaliplatin, a synergic
      effect with radiation was measured only when incubated at a concentration higher
      than its IC50. Conversely, concomitant treatment with cisplatin did not result in
      a synergic effect, as in fact a radioprotective effect was measured on the F98
      cells. In conclusion, among the five platinum compounds tested, carboplatin and
      Lipoplatin(TM) showed the best radiosensitizing effect. Lipoplatin(TM) seems the
      most promising since it led to the best cellular incorporation and has already
      been reported to be less neurotoxic than other platinum compounds.

PMID- 19760368
TI  - Zinc deficiency in chronic kidney disease: is there a relationship with adipose
      tissue and atherosclerosis?
AB  - Cardiovascular complications caused by an accelerated atherosclerotic disease
      consist the major cause of morbidity and mortality in patients with chronic
      kidney disease (CKD). These patients present multiple atherosclerotic risk
      factors, considered traditional, as well as nontraditional risk factors such as
      inflammation and oxidative stress. These complications are also seen in obesity,
      in which endothelial dysfunction is one of the early stages of atherosclerosis.
      The impact of trace metal deficiencies on this process is not well studied in
      patients with CKD and in obese people, although the influence of trace elements
      depletion, particularly zinc (Zn), may have significant clinical implications.
      This brief review describes the functions of Zn as well as the respective role of
      this trace element in atherosclerosis processes, with a particular emphasis on
      obese patients with chronic kidney disease.

PMID- 19760367
TI  - Identification and characterization of a novel Waxy allele from a Yunnan rice
      landrace.
AB  - Low amylose content (AC) is a desirable trait for rice (Oryza sativa L.) cooking
      quality and is selected in soft rice breeding. To gain a better understanding of
      the molecular mechanism controlling AC formation, we screened 83 Yunnan rice
      landraces in China and identified a rice variety, Haopi, with low AC. Genetic
      analyses and transgenic experiments revealed that low AC in Haopi was controlled
      by a novel allele of the Wx locus, Wx(hp), encoding a granule-bound starch
      synthase (GBSSI). Sequence comparisons of Wx(hp) and Wx(b) alleles (from
      Nipponbare) showed several nucleotide changes in the upstream regulatory regions
      (including the promoter, 5'-untranslated region, and first intron 5' splicing
      junction site). Interestingly, these changes had no obvious effect on the
      expression level and splicing efficiency of Wx transcripts. In addition, an
      examination of the coding region revealed that the Wx(hp) allele carries an A-to
      G change at nucleotide position +497 from the start codon, resulting in an
      Asp(165)/Gly(165) substitution. The amino acid substitution had no detectable
      effects on GBSSI activity in vitro; however, it notably reduced the binding of
      GBSSI to starch granules, resulting in a reduction of AC in rice seeds. Moreover,
      three other Yunnan landraces with low AC also carry a nucleotide substitution
      identical to Haopi at the +497 position of the Wx gene, suggesting common
      ancestry. Based on the single-nucleotide polymorphism, we have developed a new
      derived cleaved amplified polymorphic sequence marker for use in breeding
      practice to manipulate AC in rice endosperm.

PMID- 19760369
TI  - [Vaccination strategies against HPV. Recommendations from a European
      perspective].
AB  - Most countries in Western Europe have recommended human papillomavirus (HPV)
      vaccination for the prevention of cervical cancer. The burden of cervical cancer
      remains high worldwide with regional differences in incidence rates and
      mortality. Due to varying conditions in health care systems and nationwide data
      in the individual European countries, there are slightly different cervical
      cancer prevention strategies. There is an overall consensus to monitor the public
      health impact of HPV vaccines. Despite having different prevention strategies and
      vaccination recommendations in the individual European countries, consideration
      of how to evaluate and coordinate pan-European surveillance measures should be
      taken into account.

PMID- 19760370
TI  - Common bile duct injury following laparoscopic cholecystectomy in the setting of
      sinistroposition of the galladder and biliary confluence: a case report.
AB  - INTRODUCTION: A bile duct injury occurred to a 64-year-old female with highly
      aberrant bile ducts due to sinistroposition. Methods of potential injury
      avoidance are discussed. MATERIALS AND METHODS: A patient underwent elective
      laparoscopic cholecystectomy for symptomatic cholelithiasis. A left-sided
      gallbladder was diagnosed intraoperatively. Three days later, the patient
      presented with jaundice and rising liver function tests. The patient was referred
      to our institution for suspected bile duct injury. Endoscopic retrograde
      cholangiopancreatography showed complete occlusion of the common bile duct. A
      percutaneous transhepatic tube was placed in the bile ducts for decompression.
      During later operative exploration, a left-sided common hepatic duct was
      discovered. Review of preoperative imaging confirmed that the right hepatic duct
      crossed superior to the umbilical portion of the left portal vein and that
      segment 4 ducts drained into the right anterior sectional bile duct. CONCLUSION:
      This case describes an extremely rare anomaly associated with an injury to the
      common bile duct during laparoscopic cholecystectomy. Knowledge of the complex
      and unusual alterations in biliary anatomy, which may accompany sinistroposition
      of the gallbladder, should aid in avoidance of such injuries in the future.

PMID- 19760371
TI  - Laparoscopic resection for inflammatory bowel disease: outcomes from a nationwide
      sample.
AB  - BACKGROUND AND AIMS: A significant proportion of patients with inflammatory bowel
      diseases (IBD) require surgery. While the majority of these are open procedures
      (OP), there is recent interest in laparoscopic resection (LS). There are no
      nationwide comparison of outcomes between LS and OP. METHODS: We used data from
      the Nationwide Inpatient Sample 2004 and identified patients with IBD who
      underwent ileocolonic/colonic resection using appropriate ICD-9 codes. Procedures
      were considered to be laparoscopic if they had concomitant codes for laparoscopy
      (International Classification of Diseases, Ninth edition, clinical modification
      54.21/54.51). Multivariate regression was performed to identify independent
      predictors and outcomes. RESULTS: There were 209,206 IBD hospitalizations
      included in the study among whom, 884 underwent laparoscopic resections (5.3%).
      On multivariate analysis, fistulizing disease (odds ratio (OR) 0.35, 95%
      confidence interval (CI) 0.21-0.59) and emergent admission (OR 0.59, 95% CI 0.39
      0.90) were negative while annual hospital IBD surgical volume of >50 procedures
      (OR 2.0, 95% CI 1.14-3.52) were positively associated with LS. LS was associated
      with a significantly lower proportion of postoperative complications (27.1% vs
      35.4%, p < 0.001) and shorter postoperative length of stay compared to OP (-1.9
      days, 95% CI -3.2 to -0.6 days). Propensity score adjustment for nonrandom
      allocation of patients into the treatment groups neutralized the OR for
      postoperative complication (OR 0.82) but not length of stay (-1.7 days).
      CONCLUSION: LS had no increase in rate of complications and was associated with a
      shorter postoperative length of stay.

PMID- 19760372
TI  - Rudolf Nissen (1896-1981)-perspective.
AB  - INTRODUCTION: Rudolf Nissen was one of the outstanding general surgeons of the
      last century. Between the years 1921 and 1933, he was the pupil and protege of
      the famous surgeon Ferdinand Sauerbruch. He was nominated professor of surgery in
      1930. Forced by the Nazi-Regime to resign his position, Nissen emigrated in 1933
      first to Turkey and then in 1939 to the USA. Here, he held positions in hospitals
      at New York. Having been appointed to the Chair of Surgery at the University of
      Basle, Switzerland, he returned to Europe in 1952. Nissen was a critical prolific
      writer and excellent researcher, surgeon, and teacher. CONCLUSION: The first
      successful pneumectomy and lung lobectomy in man, as well as the description of
      surgical pathophysiology and treatment of gastroesophageal reflux disease,
      including hiatus hernia, are considered to be his most important pioneer work.

PMID- 19760373
TI  - A controversy that has been tough to swallow: is the treatment of achalasia now
      digested?
AB  - Esophageal achalasia is a rare neurodegenerative disease of the esophagus and the
      lower esophageal sphincter that presents within a spectrum of disease severity
      related to progressive pathological changes, most commonly resulting in
      dysphagia. The pathophysiology of achalasia is still incompletely understood, but
      recent evidence suggests that degeneration of the postganglionic inhibitory
      nerves of the myenteric plexus could be due to an infectious or autoimmune
      mechanism, and nitric oxide is the neurotransmitter affected. Current treatment
      of achalasia is directed at palliation of symptoms. Therapies include
      pharmacological therapy, endoscopic injection of botulinum toxin, endoscopic
      dilation, and surgery. Until the late 1980s, endoscopic dilation was the first
      line of therapy. The advent of safe and effective minimally invasive surgical
      techniques in the early 1990s paved the way for the introduction of laparoscopic
      myotomy. This review will discuss the most up-to-date information regarding the
      pathophysiology, diagnosis, and treatment of achalasia, including a historical
      perspective. The laparoscopic Heller myotomy with partial fundoplication
      performed at an experienced center is currently the first line of therapy because
      it offers a low complication rate, the most durable symptom relief, and the
      lowest incidence of postoperative gastroesophageal reflux.

PMID- 19760374
TI  - Plectin-1 is a biomarker of malignant pancreatic intraductal papillary mucinous
      neoplasms.
AB  - INTRODUCTION: Pancreatic intraductal papillary mucinous neoplasms (IPMN) are now
      identified with increasing frequency. The detection of carcinoma in IPMN is
      difficult and suffers from high false-positive and false-negative rates, often
      resulting in inappropriate treatment decisions. Improved detection of malignancy
      using novel biomarkers may therefore improve diagnostic accuracy. One such
      promising novel biomarker is Plectin-1 (Plec-1). METHODS: Using
      immunohistochemistry, Plec-1 expression was assayed in benign (low and moderate
      dysplasia, n = 6) as well as malignant IPMN (high-grade dysplasia and invasive
      carcinoma, n = 31) and lymph node metastases from carcinoma arising in IPMN (n =
      12). Furthermore, cyst fluids from benign (n = 3) and malignant IPMN (n = 4) were
      evaluated for Plec-1 expression. RESULTS AND DISCUSSION: Twenty-six of 31
      malignant IPMN and all 12 lymph node metastases were Plec-1 positive. In
      contrast, only one of six benign IPMN expressed Plec-1. The specificity of Plec-1
      in distinguishing malignant IPMN from benign IPMN was 83% and its sensitivity
      84%. Furthermore, all (four out of four) cyst fluids from malignant IPMN, but
      none of the three benign IPMN, were Plec-1 positive. These data support Plec-1 as
      an excellent biomarker for the early detection of carcinoma arising in IPMN.

PMID- 19760375
TI  - Incidence rate of pulmonary embolism in Germany: data from the federal
      statistical office.
AB  - With the introduction of Diagnosis Related Groups (DRG) for reimbursement in 2003
      detailed description of the prevalence of pulmonary embolism (PE) in hospitalized
      patients in Germany was possible for the first time. Thus we estimated the
      incidence rate of PE in Germany. Detailed lists of all PE coded as I26 performed
      in 2005, 2006 and 2007 were provided by the Federal Statistical Office. In
      addition age- and gender-adjusted incidence rates were calculated for all cases
      for which PEs were coded. In 2005 a total of 67,351, in 2006 a total of 69,234
      and in 2007 a total of 71,223 PEs (I26.0) were coded either as principal or
      secondary diagnosis in German hospitals. 54-57% of all PEs were coded as
      principal diagnosis. Age- and gender adjusted incidence of PEs raised with
      increasing ages and were higher in males aged 30-49 and 50-69 years than in
      females within the same age groups. Up to 60% of all PE documented in females
      occurred within the 8th and 9th decade of life. Departments of Geriatric
      Medicine, Haematology and Oncology and Pneumology had the highest rates of
      intrahospital PEs documented as secondary diagnosis. The presented data are
      derived from the most reliable data base for the estimation of PE in Germany, and
      the analysis shows that PE is still a relevant problem. They do not give any
      information about the individual settings and preventability of PEs. An
      accompanying analysis of hospital and pre-hospital settings is mandatory to
      recognize possible strategies to prevent PEs more effectively.

PMID- 19760376
TI  - [Free mobile intra-abdominal "tumor"].
AB  - The rare condition of an accidentally discovered 3 cm sized tumor in the abdomen
      is reported which was completely free and migrating within the abdominal cavity.
      Initially it was detected by ultrasound and thereafter reconfirmed in several CT
      scans over 2.5 years. Surprisingly the tumor was localized at different sites.
      Finally it was removed laparoscopically. Histopathology revealed that it was most
      probably a calcified appendix epiploicum separated from the colon.

PMID- 19760377
TI  - [Quality criteria for treatment of colorectal cancer. From a surgeon's
      viewpoint].
AB  - The surgeon is the key "prognosis factor" for colorectal cancer. For this reason
      quality criteria were recently established (including minimum numbers) in order
      to treat patients who are entitled to the best quality of care and to improve the
      prognosis. The aim of this study was to critically discuss the existing demands
      on the surgeon based on the current literature and our own results and to
      formulate evidence-based quality criteria for surgical clinics. After reviewing
      the current literature criteria were compiled, discussed and finally presented in
      a summarized form. These are based on current developments on the diagnostic and
      therapy of large intestine and colorectal carcinoma. New developments of the
      German Cancer Society for planning of organ centers are incorporated. The
      quintessence of our study is that the number of cases alone is not decisive for
      the success of therapy. Important are the application of the correct surgical
      oncology operation procedure, adherence to standards and the training of
      surgeons. Following the S3 guidelines stage-oriented therapy should additionally
      be carried out in a structured sequence. This includes an interdisciplinary
      decision making on the diagnostic and therapy strategy (tumor board). The
      organization structure of the hospital (teams, tumor board, emergency care with
      intensive care unit, emergency diagnostic and options for interventional
      measures) can be more important than the hospital case numbers alone. These
      demands which have been evaluated from published data and own results are
      designed to raise the therapy of colorectal cancer to the best possible level of
      quality and to effect a further improvement in the prognosis.

PMID- 19760378
TI  - [Citation characteristics of German authors in "Der Chirurg": hegemony of the
      impact factor].
AB  - Characteristics of citation and language in publications of German authors from
      the journal "Der Chirurg" (vol 78, 2007) were analysed. Out of a total of 3,342
      citations, 756 (22.62%) were from German authors with 248 (32.8) self-citations.
      The hegemony of the impact factor in science, research and education is
      critically discussed. The imbalance between the number of surgeons in the US and
      United Kingdom (66,032) and surgeons in the German speaking countries in Europe
      (25,300) is compared with respect to the counting methods used to create the
      impact factor of a journal. The creation of an independent impact factor in
      Europe and the development of an EU-based citation data bank which allows
      unselected access to national language scientific literature are strongly needed.

PMID- 19760379
TI  - [Clinical anatomy of the paranasal sinuses. Descriptive anatomy, topography and
      important variations].
AB  - Detailed knowledge of the complicated anatomy and topography of the paranasal
      sinuses is an essential requirement for successful surgery in this region. The
      topographical relationship to essential neighbouring structures (vessels, nerves
      and spaces) must be borne in mind. Typical landmarks play a particularly
      important role, especially for reliable orientation in endoscopic procedures.
      Therefore, it must be stressed that detailed anatomical knowledge of the
      complicated nasal and paranasal architecture is very important for the success of
      nasal and paranasal surgery, as well as for the avoidance of serious
      complications. However, this knowledge can only be acquired by performing
      numerous dissections of the nasal and paranasal system once a good theoretical
      grasp of the various structures, regions and their nomenclature has been gained.
      Common anatomical variations, which may lead to complicated and hazardous changes
      in normal anatomy, are also of particular importance and the surgeon must be
      familiar with these variations.

PMID- 19760380
TI  - [Examination questions for board certification in ENT. Guiding principles for the
      oral examination].

PMID- 19760381
TI  - [Intrasinusal and extrasinusal space-occupying lesion of the maxillary sinus].
AB  - A 72-year-old healthy male patient presented with a painless mass on the left
      cheek which had been growing for 3 months as well as swollen cervical lymph
      nodes. Computed tomography revealed a space-occupying lesion on the facial wall
      of the sinus. Biopsy and histological examination of the lesion and a lymph node
      revealed Hodgkin's and Sternberg-Reed cells. The diagnosis of Hodgkin's disease
      was confirmed immunohistologically by the detection of atypical blast cell
      infiltrates with reactivity for CD30 and CD15 surface antigens.

PMID- 19760382
TI  - [Long-term effectiveness of different dietary strategies.    Comparison of
      different compositions of fat, protein and carbohydrates].

PMID- 19760383
TI  - Benzyl isothiocyanate exhibits anti-inflammatory effects in murine macrophages
      and in mouse skin.
AB  - Benzyl isothiocyanate (BITC) is detected in abundance in Brassica vegetables, and
      some previous studies have demonstrated that BITC may potentially function as a
      chemopreventive agent in humans. This study examined whether BITC inhibits
      lipopolysaccharide (LPS)-induced inflammatory responses in Raw 264.7 macrophages
      and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear edema formation. The
      treatment of macrophages with various concentrations of BITC resulted in a dose
      dependent reduction in the LPS-induced secretion of interleukin (IL)-1beta, TNF
      alpha, and IL-6 and their corresponding mRNA levels, as well as in the production
      of nitric oxide and PGE(2). Consistent with these findings, BITC inhibited the
      LPS-induced expressions of inducible nitric oxide synthase (iNOS) and
      cyclooxygenase (COX)-2 proteins and their corresponding mRNAs. BITC inhibited LPS
      induced phosphorylation and the degradation of the inhibitor of kappaBalpha,
      translocation of p65 into the nucleus, and the DNA binding activity and
      transcriptional activity of NFkappaB. Moreover, the LPS-stimulated
      phosphorylation of extracellular signal regulated kinase (ERK)1/2 and Akt was
      suppressed by BITC. BITC also inhibited ear edema formation and the protein
      expression of iNOS and COX-2 in mouse skin treated with TPA. We demonstrate that
      BITC is a potent anti-inflammatory agent, and the anti-inflammatory properties of
      BITC may result from the downregulation of NFkappaB signaling.

PMID- 19760384
TI  - [Coagulation management in multiple trauma].
AB  - More than 25% of polytraumatized patients present in the emergency department
      with a coagulopathy which results in a 4-fold increase in mortality. The
      detection of microvascular bleeding is the major clinical indicator. Measurement
      of fibrinogen, activated partial thromboplastin time and prothrombin time as well
      as thrombelastometry are required. A prerequisite for the substitution of
      coagulation factors and platelets is an immediate surgical control of bleeding
      and correction of hypothermia, acidosis and hypocalcemia. The goals for platelet
      count, fibrinogen, PT and aPTT are well established. The use of an algorithm for
      transfusion and coagulation management results in optimized therapy and improved
      outcome. Substituted coagulation products are only effective if hyperfibrinolysis
      has been corrected before. The administration of fibrinogen corrects the
      coagulation factor that is critically reduced earliest, improves global
      coagulation tests and reduced mortality in some studies. The dose required (3-5
      g) can be calculated by a formula. Fresh frozen plasma is given in a 1:1 ratio to
      red blood cells or at least 20-40 ml/kg body weight. A clear advantage for
      survival has not yet been shown and some of the risks include insufficient
      substitution of fibrinogen and transfusion-related acute lung injury. Goals for
      the administration of platelet concentrates depend on the acuity of bleeding,
      injury pattern (e.g. head trauma) and clinical signs of microvascular bleeding.
      Factor VIIa remains an off-label rescue therapy if bleeding persists despite
      optimization of preconditions and specific coagulation management.

PMID- 19760385
TI  - [Intrathoracic hernia after laparoscopic nephrectomy: clinical manifestation and
      conservative management].
AB  - Diaphragmatic hernia can be inborn as well as acquired. We report on the
      manifestation of an intrathoracic hernia after laparoscopic nephrectomy.
      Intraoperative and postoperative complications could make intense medical
      treatment or further surgery necessary. In cases of lasting abdominal discomfort
      or pulmonary symptoms after abdominal surgery, radiological investigation to
      exclude intrathoracic hernia should be considered.

PMID- 19760386
TI  - [Characterization of the EGF receptor status in penile cancer : retrospective
      analysis of the course of the disease in 45 patients].
AB  - INTRODUCTION: Therapeutic success in metastasized squamous cell carcinoma is
      poor. Some entities, such as head-and-neck tumors or non-small-cell lung cancer,
      show an over expression of the EGF receptor. In latest studies target-specific
      substances against the EGF receptor have already been combined with chemotherapy
      or radiotherapy. Some studies showed a clear advantage of this combination
      concerning remission rates as well as survival. EGF receptor status has not yet
      been examined in penile cancer, therefore, a retrospective analysis of the
      receptor status was performed in patients treated over the last 14 years and
      correlations with the clinical course were investigated. PATIENTS AND METHODS:
      The analysis included 45 patients, who underwent primary or secondary treatment
      at the Department of Urology of the University of Essen during 1990 to 2004.
      Histological preparations existed for 44 patients. Using immunohistochemistry the
      expression of EGF receptors was determined. RESULTS: A total of 25 patients were
      primarily without positive lymph nodes (6 times cN0 and 19 times pN0), while 20
      patients had pathologically proven lymph node metastases and 3 of them also had
      hematogeneous metastases. Out of 42 patients with follow-up 18 are still living
      of whom only 3 primarily had positive lymph nodes. These patients received
      adjuvant chemotherapy after resection. Out of the remaining 15 patients, 4
      primarily N0 patients developed a lymphogenic recurrence, which was also resected
      and 3 patients also received adjuvant chemotherapy. Of the patients 24 died, 22
      because of penile cancer. Of these 22 patients 16 primarily had positive lymph
      nodes and 5 of them also had an extensive primary tumor. Surgery was the
      treatment of choice in these cases and 10 patients also received chemotherapy.
      Nevertheless, 15 patients developed several recurrences. Distinguishing primarily
      node-negative and node-positive patients, the Kaplan-Meyer survival curves showed
      a significant difference (p<0.001). Median overall survival was 55.5 compared to
      34 months and median 5-year survival was 76.9% compared to 15.8%. Of the tumors
      40 out of 44 (91%) showed a positive or strong positive EGF receptor expression
      of the primary tumor as well as of the metastases. A correlation between EGF
      receptor expression and survival could not be shown. CONCLUSION: Clinical data
      underline the prognostic value of the primary lymph node status as well as the
      therapeutic value of an ileoinguinal lymphadenectomy and adjuvant chemotherapy.
      It could also be shown that inductive chemotherapy is not very successful. EGF
      receptor expression was high and comparable to other squamous cell carcinomas,
      but there was no correlation to survival.

PMID- 19760387
TI  - [Day-case holmium laser enucleation and mechanical morcellation of the prostate].
AB  - BACKGROUND: Holmium laser enucleation of the prostate (HoLEP) is increasingly
      being used as an alternative to transurethral resection of the prostate (TURP)
      and transurethral electrovaporisation of the prostate (TVP), the"gold standard"
      procedures for treating symptomatic benign prostatic hyperplasia. Mechanical
      tissue morcellation was introduced in 1998, and its efficiency could be improved.
      We investigated the efficiency and complication rate of a morcellator in a day
      case setting. METHODS: From 2004 to 2008, 137 men were treated with an 80W
      holmium:YAG laser and subsequent tissue morcellation. RESULTS: The average
      patient age was 68.0+/-7.1 (51-86) years. Morcellation time was 8.6+/-6.8 (1-35)
      min. The weight of the resected tissue was 36.6+/-30.0 (2-175) g. The total time
      for the procedure was 69.6+/-28.7 (29-150) min, and the efficiency of
      morcellation was 5.0+/-2.6 (0.2-11.5) g/min. The complication rate due to
      morcellation was 4.3%. CONCLUSION: HoLEP with mechanical morcellation is safe
      even in a day-case setting. The total procedure time approximates that for TURP,
      so a longer theatre time loses significance as an argument against the method.
      Complications are rare and not severe. Further technical improvement is
      desirable.

PMID- 19760388
TI  - [Acute pain in adults, including perioperative pain management].
AB  - The vast majority of surgical patients suffer from postoperative pain, which has
      an enormous influence on quality of life and the progress of the stationary stay.
      This article gives practical advice on perioperative pain management, taking into
      consideration the European Association of Urology guidelines for 2009 and the S3
      guideline on the treatment of acute perioperative and traumatic pain.

PMID- 19760389
TI  - MlAG12: a Triticum timopheevii-derived powdery mildew resistance gene in common
      wheat on chromosome 7AL.
AB  - Wheat powdery mildew is an economically important disease in cool and humid
      environments. Powdery mildew causes yield losses as high as 48% through a
      reduction in tiller survival, kernels per head, and kernel size. Race-specific
      host resistance is the most consistent, environmentally friendly and, economical
      method of control. The wheat (Triticum aestivum L.) germplasm line NC06BGTAG12
      possesses genetic resistance to powdery mildew introgressed from the AAGG
      tetraploid genome Triticum timopheevii subsp. armeniacum. Phenotypic evaluation
      of F(3) families derived from the cross NC06BGTAG12/'Jagger' and phenotypic
      evaluation of an F(2) population from the cross NC06BGTAG12/'Saluda' indicated
      that resistance to the 'Yuma' isolate of powdery mildew was controlled by a
      single dominant gene in NC06BGTAG12. Bulk segregant analysis (BSA) revealed
      simple sequence repeat (SSR) markers specific for chromosome 7AL segregating with
      the resistance gene. The SSR markers Xwmc273 and Xwmc346 mapped 8.3 cM distal and
      6.6 cM proximal, respectively, in NC06BGTAG12/Jagger. The multiallelic Pm1 locus
      maps to this region of chromosome 7AL. No susceptible phenotypes were observed in
      an evaluation of 967 F(2) individuals in the cross NC06BGTAG12/'Axminster' (Pm1a)
      which indicated that the NC06BGTAG12 resistance gene was allelic or in close
      linkage with the Pm1 locus. A detached leaf test with ten differential powdery
      mildew isolates indicated the resistance in NC06BGTAG12 was different from all
      designated alleles at the Pm1 locus. Further linkage and allelism tests with five
      other temporarily designated genes in this very complex region will be required
      before giving a permanent designation to this gene. At this time the gene is
      given the temporary gene designation MlAG12.

PMID- 19760390
TI  - Family-based mitochondrial association study of traits related to type 2 diabetes
      and the metabolic syndrome in adolescents.
AB  - AIMS/HYPOTHESIS: There has been much focus on the potential role of mitochondria
      in the aetiology of type 2 diabetes and the metabolic syndrome, and many case
      control mitochondrial association studies have been undertaken for these
      conditions. We tested for a potential association between common mitochondrial
      variants and a number of quantitative traits related to type 2 diabetes in a
      large sample of >2,000 healthy Australian adolescent twins and their siblings,
      many of whom were measured on more than one occasion. METHODS: To the best of our
      knowledge, this is the first mitochondrial association study of quantitative
      traits undertaken using family data. The maternal inheritance pattern of
      mitochondria means established association methodologies are unsuitable for
      analysis of mitochondrial data in families. We present a methodology, implemented
      in the freely available program Sib-Pair for performing such an analysis.
      RESULTS: Despite our study having the power to detect variants with modest
      effects on these phenotypes, only one significant association was found after
      correction for multiple testing in any of four age groups. This was for mt14365
      with triacylglycerol levels (unadjusted p = 0.0006). This association was not
      replicated in other age groups. CONCLUSIONS/INTERPRETATION: We find little
      evidence in our sample to suggest that common European mitochondrial variants
      contribute to variation in quantitative phenotypes related to diabetes. Only one
      variant showed a significant association in our sample, and this association will
      need to be replicated in a larger cohort. Such replication studies or future meta
      analyses may reveal more subtle effects that could not be detected here because
      of limitations of sample size.

PMID- 19760392
TI  - Laparoscopic epilepsy surgery.

PMID- 19760393
TI  - Wanted: early goal-directed therapy for septic shock--dead or alive, but not
      critically ill!

PMID- 19760394
TI  - Changes in peroxisome proliferator-activated receptor-gamma activity in children
      with septic shock.
AB  - PURPOSE: To assess changes in peroxisome proliferator-activated receptor-gamma
      (PPARgamma) in peripheral blood mononuclear cells (PBMC) from critically ill
      children with sepsis. Additionally, to investigate the effects of sepsis on the
      endogenous activator of PPARgamma, 15-deoxy-(12,14)-PGJ(2) (15d-PGJ(2)), and the
      downstream targets of PPARgamma activity, adiponectin and resistin. METHODS:
      Single-center, prospective case-control study in critically ill children with
      systemic inflammatory response syndrome, sepsis or septic shock. RESULTS:
      PPARgamma nuclear protein expression was decreased but PPARgamma activity was
      increased in PBMC from children with septic shock compared with controls.
      PPARgamma activity on day 1 was significantly higher in patients with higher
      pediatric risk of mortality (PRISM) score compared with controls [mean 0.22
      optical density (OD) +/- standard error of the mean (SEM) 0.03 versus 0.12 OD +/-
      0.02; p < 0.001]. Patients with resolved sepsis had increased levels of the
      endogenous PPARgamma ligand, 15d-PGJ(2), compared with patients with systemic
      inflammatory response syndrome (SIRS) and septic shock (77.7 +/- 21.7 versus 58
      +/- 16.5 pg/ml; p = 0.03). Plasma high-molecular-weight adiponectin (HMWA) and
      resistin levels were increased in patients with septic shock on day 1 and were
      significantly higher in patients with higher PRISM scores. Nonsurvivors from
      sepsis had higher resistin levels on the first day of hospitalization compared
      with survivors from septic shock [660 ng/ml, interquartile range (IQR) 585-833
      ng/ml versus 143 ng/ml, IQR 66-342 ng/ml; p < 0.05]. CONCLUSIONS: Sepsis is
      associated with altered PPARgamma expression and activity in PBMC. Plasma
      adipokines correlate with risk of mortality scores in sepsis and may be useful
      biomarkers. Further studies are needed to understand the mechanisms underlying
      changes in PPARgamma in sepsis.

PMID- 19760395
TI  - Prospective meta-analysis using individual patient data in intensive care
      medicine.
AB  - Meta-analysis is a technique for combining evidence from multiple trials.
      However, meta-analyses of studies with substantial heterogeneity among patients
      within trials-common in intensive care-can lead to incorrect conclusions if
      performed using aggregate data. Use of individual patient data (IPD) can avoid
      this concern, increase the power of a meta-analysis, and is useful for exploring
      subgroup effects. Barriers exist to IPD meta-analysis, most of which are overcome
      if clinical trials are designed to prospectively facilitate the incorporation of
      their results with other trials. We review the features of prospective IPD meta
      analysis and identify those of relevance to intensive care research. We identify
      three clinical questions, which are the subject of recent or planned randomised
      controlled trials where IPD MA offers advantages over approaches using aggregate
      data.

PMID- 19760396
TI  - Detection of carbon dioxide thresholds using low-flow sidestream capnography in
      ventilated preterm infants.
AB  - BACKGROUND: Monitoring CO2 levels in preterm infants receiving mechanical
      ventilation is designed to avoid the harmful consequences of hypocapnia or
      hypercapnia. Capnography is of questionable accuracy for monitoring PCO2 in
      preterm infants. OBJECTIVES: To determine the accuracy of sidestream capnography
      in ventilated preterm infants by comparing end-tidal carbon dioxide (EtCO2)
      values to mixed venous carbon dioxide pressure (PvCO2) and to transcutaneous
      carbon dioxide pressure (TcPCO2). METHODS: Simultaneous recordings of EtCO2,
      TcPCO2 and PvCO2 in 37 ventilated preterm infants. The PvCO2-EtCO2 gradient was
      calculated. The Bland-Altman technique and the intra-class correlation
      coefficient (ICC) were used to assess agreement between methods. The area under
      the curve (AUC) was calculated. RESULTS: Ninety-nine EtCO2/PvCO2 pairs were
      studied from 37 preterm infants with a mean gestational age of 27.7 +/- 1.9 weeks
      and a mean birth weight of 1,003 +/- 331 g. The mean PvCO2-EtCO2 gradient was
      11.2 +/- 8.0 mmHg, and the ICC was 0.28. The mean PvCO2-TcPCO2 gradient was 0 +/-
      7.8 mmHg, and the ICC was 0.78. AUCs for EtCO2 and TcPCO2 were similar in
      detecting high or low PvCO2. CONCLUSION: Despite an insufficient correlation
      between EtCO2 and PvCO2, capnography was able to detect low and high CO2 warning
      levels with a similar efficacy to that of TcPCO2, and may therefore be of
      clinical interest.

PMID- 19760397
TI  - Anatomic and arthroscopic study of the medial meniscal horns' insertions.
AB  - The insertions of the menisci to the tibia are the most important restraints to
      extrusion from the knee joint, and are vital for the functional integrity of the
      menisci. The aim of the present study was to determine variations of tibial
      insertions of the medial menisci (MM) in newborn cadavers macroscopically and in
      adults by arthroscopy. Neonatal part of this study was performed on 40 knee
      joints of 20 Caucasian neonatal cadavers. Adult part was performed on 41
      Caucasian adults, whose ages were between 17 and 66 unilaterally by arthroscopy.
      In neonatal cadavers, according to its insertion, anterior horn of MM was
      classified in five groups and type 4, in which it was inserted to the transverse
      ligament, was determined the most frequent one (45%) and posterior horn of MM was
      classified in three groups and type 3, in which it was inserted to both the
      posterior intercondylar area of tibia and medial tubercle of intercondylar
      eminence was determined the most frequent one (50%). In adults, anterior end of
      MM was most frequently inserted to both anterior intercondylar area of tibia and
      transverse ligament (76%) and posterior horn of MM was inserted to the posterior
      intercondylar area of tibia in all of them. This study provides comparative
      information about insertion of the MM for neonatals and adults, not to evaluate
      the variants of the insertion of the MM as a tear of the anterior cruciate
      ligament or a meniscal tear and not to complicate arthroscopy.

PMID- 19760398
TI  - The relationship of lateral anatomic structures to exiting guide pins during
      femoral tunnel preparation utilizing an accessory medial portal.
AB  - Anatomic reconstruction of the anterior cruciate ligament through an accessory
      medial portal has become increasingly popular. The purpose of this study is to
      describe the relationship of guide pin exit points to the lateral anatomic
      structures when preparing the anterior cruciate ligament femoral tunnel through
      an accessory medial portal. We utilized seven fresh frozen cadaveric knees.
      Utilizing an anteromedial approach, a guide wire was placed into the center of
      each bundle's footprint. Each guide wire was advanced through the lateral femoral
      cortex. The guide pins were passed at 90, 110, and 130 degrees of knee flexion.
      The distances from each guide pin to the closest relevant structures on the
      lateral side of the knee were measured. At 90 degrees the posterolateral bundle
      guide pin was closest to the lateral condyle articular cartilage (mean 5.4 +/-
      2.2 mm) and gastrocnemius tendon (mean 5.7 +/- 2.1 mm). At 110 degrees the
      posterolateral bundle pin was closest to the gastrocnemius tendon (mean 4.5 +/-
      3.4 mm). At 130 degrees the posterolateral bundle pin was closest to the
      gastrocnemius tendon (mean 7.2 +/- 5.5 mm) and lateral collateral ligament (mean
      6.8 +/- 2.1 mm). At 90 degrees the anteromedial bundle guide pin was closest to
      the articular cartilage (mean 2.0 +/- 2.0 mm). At 110 degrees the anteromedial
      bundle pin was closest to the articular cartilage (mean 7.4 +/- 3.5 mm) and
      gastrocnemius tendon (mean 12.3 +/- 3.1 mm). At 130 degrees the AM bundle pin was
      closest to the gastrocnemius tendon (mean 8.2 +/- 3.2 mm) and LCL (mean 15.1 +/-
      2.9 mm). Neither guide pin (anteromedial or posterolateral bundle) put the
      peroneal nerve at risk at any knee flexion angle. At low knee flexion angles the
      anteromedial and posterolateral bundle guide pins closely approximated multiple
      lateral structures when using an accessory medial arthroscopic portal. Utilizing
      higher flexion angles increases the margin of error when preparing both femoral
      tunnels. During preparation of the anterior cruciate ligament femoral tunnel
      through an accessory anteromedial portal the tunnels should be drilled in at
      least 110 degrees of knee flexion in order to move guide pin exit points away
      from important lateral knee structures.

PMID- 19760399
TI  - A meta-analysis of the effect of neuromuscular training on the prevention of the
      anterior cruciate ligament injury in female athletes.
AB  - Female athletes are more prone to anterior cruciate ligament (ACL) injury than
      their male counterparts, presumably because of anatomical, hormonal, and
      neuromuscular differences. Of these three, only the neuromuscular component can
      be modified by preventive exercise. We aimed to evaluate the effect of a
      neuromuscular protocol on the prevention of ACL injury by performing meta
      analysis, and to identify essential factors by subgroup analysis. An extensive
      literature review was conducted to identify relevant studies, and eventually,
      only seven randomized controlled trials or prospective cohort studies were
      included in the analysis. The odds ratios (OR) and the confidence interval (CI)
      for the overall effects of training and of potentially contributory factors were
      estimated. The OR and the 95% CI for the overall effect of the preventive
      training were 0.40 and [0.27, 0.60], respectively. Subgroup analysis revealed
      that an age under 18, soccer rather than handball, pre- and in-season training
      rather than either pre- or in-season training, and the plyometrics and
      strengthening components rather than balancing were significant. Meta-analysis
      showed that pre- and in-season neuromuscular training with an emphasis on
      plyometrics and strengthening exercises was effective at preventing ACL injury in
      female athletes, especially in those under 18 years of age. Further study is
      required to develop a relevant training program protocol of appropriate
      intensity.

PMID- 19760400
TI  - Histological evaluation of juvenile osteochondritis dissecans of the knee: a case
      series.
AB  - Osteochondritis dissecans (OCD) is an acquired, potentially reversible idiopathic
      disease of subchondral bone resulting in delamination and sequestration. Although
      juvenile-type OCD lesions typically appear stable on superficial examination,
      conservative treatment results in cure in approximate 50% of patients. We
      hypothesized that juvenile-type OCD lesions exhibit an underlying instability
      despite stability at the articular surface and this underlying instability might
      underlie the lack of effectiveness of conservative treatment. In this study,
      osteochondral cylindrical tissue samples obtained from stable juvenile OCD
      lesions located at the medial femoral condyle (classical site) were examined.
      Eight patients with symptomatic juvenile-type OCD at the classical site underwent
      arthroscopy. Osteochondral cylindrical tissue samples were obtained from the
      central portion using a biopsy needle. The samples underwent macroscopic and
      microscopic examination. All cylindrical samples demonstrated macroscopic
      separation. On microscopic examination, no degenerative changes in articular
      cartilage and no bone necrosis were observed. Histological examination revealed
      two distinct patterns in the samples: (1) thick homogeneous hyaline cartilage
      alone with little fibrous tissue surrounding areas of separation and (2) nearly
      normal, thin hyaline cartilage above a mixed layer of hyaline cartilage and
      subchondral trabeculae and fibrous/fibro-cartilaginous tissue at the areas of
      separation, indicating delayed or nonunion. Pathological findings in stable
      juvenile OCD lesions indicate an underlying instability at deeper layers of
      articular cartilage and poor healing at areas of separation. Improved knowledge
      of the histology of juvenile-type OCD lesions may support surgical treatment.
      Early marrow stimulation and/or fixation may be the treatment of choice to
      promote healing even in macroscopically stable juvenile-type OCD lesions.

PMID- 19760401
TI  - Full-thickness cartilage lesion do not affect knee function in patients with ACL
      injury.
AB  - There is debate in the literature regarding the impact of full-thickness
      cartilage lesion on knee function in patients with ACL injury. The hypothesis of
      the current study is that a full-thickness cartilage lesion at the time of ACL
      reconstruction does not influence knee function as measured by the Knee injury
      and Osteoarthritis Outcome Score (KOOS) in patients with ACL injury. Of the 4,849
      primary ACL surgery cases in the Norwegian National Knee Ligament Registry as of
      12 December 2007, 30 patients met the following inclusion criteria: a full
      thickness cartilage lesion (International Cartilage Repair Society [ICRS] grades
      3 and 4), age less than 40 years, no associated pathology or meniscus injury, and
      less than 1 year between knee injury and ACL reconstruction. Each of the 30
      patients in this study group was matched with two control participants without
      cartilage lesions. Preoperatively, the patients completed the KOOS, and the
      surgeon recorded the location and size of the cartilage lesion and graded the
      cartilage injury according to ICRS standards. There were no significant
      differences between the case and control groups for any of the five subscales of
      the KOOS. A cartilage lesion was located in the medial compartment in 67% of the
      cases, in the lateral compartment in 20% of the cases, and in the patellofemoral
      joint in 13% of the cases. In conclusion, the combination of a full-thickness
      cartilage lesion and an ACL rupture did not result in inferior knee function at
      the time of the ACL reconstruction as measured by the KOOS.

PMID- 19760402
TI  - Solid-contact pH-selective electrode using multi-walled carbon nanotubes.
AB  - Multi-walled carbon nanotubes (MWCNT) are shown to be efficient transducers of
      the ionic-to-electronic current. This enables the development of a new solid
      contact pH-selective electrode that is based on the deposition of a 35-microm
      thick layer of MWCNT between the acrylic ion-selective membrane and the glassy
      carbon rod used as the electrical conductor. The ion-selective membrane was
      prepared by incorporating tridodecylamine as the ionophore, potassium
      tetrakis[3,5-bis(trifluoromethyl)phenyl]borate as the lipophilic additive in a
      polymerized methylmethacrylate and an n-butyl acrylate matrix. The potentiometric
      response shows Nernstian behaviour and a linear dynamic range between 2.89 and
      9.90 pH values. The response time for this electrode was less than 10 s
      throughout the whole working range. The electrode shows a high selectivity
      towards interfering ions. Electrochemical impedance spectroscopy and
      chronopotentiometry techniques were used to characterise the electrochemical
      behaviour and the stability of the carbon-nanotube-based ion-selective
      electrodes.

PMID- 19760403
TI  - Sulfonate group-modified FePtCu nanoparticles as a selective probe for LDI-MS
      analysis of oligopeptides from a peptide mixture and human serum proteins.
AB  - Bare FePtCu nanoparticles (NPs) are first prepared for laser
      desorption/ionization mass spectroscopy (LDI-MS) analysis as affinity probes to
      selectively trap oppositely charged analytes from a sample solution. Our present
      results demonstrate bare FePtCu NPs to be a potentially useful matrix for surface
      assisted laser desorption/ionization mass spectroscopy (SALDI-MS), for the
      analysis of small proteins and peptides. The upper detectable mass range of
      peptides was approximately 5 kDa, and the detection limit for peptides
      approximately 5 fmol. Sulfonate group-modified FePtCu nanoparticles (FePtCu
      SO(3)(-) NPs), with ionization being independent of the solution pH, can interact
      with a positively charged analyte, and the analyte-bound NPs can be separated
      from the reaction supernatant by centrifugation or an external magnetic field. An
      oligopeptide, Gly-Gly-Tyr-Arg (GGYR) from an oligopeptide mixture containing Asp
      Asp-Asp-Asp (DDDD), Gly-Gly-Gly-Gly (GGGG) and GGYR, was detected using SALDI-MS
      with FePtCu-SO(3)(-) NPs employing electrostatic interaction. Furthermore, FePtCu
      SO(3)(-) NPs can detect lysozyme (Lyz) in human serum through the electrostatic
      attraction between positively charged Lyz and FePtCu-SO(3)(-) NPs at pH 8, while
      detection of negatively charged albumin in human serum is not possible.

PMID- 19760404
TI  - Simultaneous extraction of polycyclic aromatic hydrocarbons and polychlorinated
      biphenyls in agricultural soils by pressurized liquid extraction and
      determination by gas chromatography coupled to tandem mass spectrometry.
AB  - A simple and rapid method based on pressurized liquid extraction has been
      validated for the simultaneous extraction of polychlorinated biphenyls (PCBs) and
      polycyclic aromatic hydrocarbons (PAHs) from agricultural soil samples. Effective
      extraction was carried out in less than 17 min for all the studied compounds, and
      good recoveries were obtained for PAHs and PCBs, ranging from 70% to 112%, when
      blank samples were spiked at 2.5 microg kg(-1), except for naphthalene with
      recoveries close to 40%. The separation and determination were performed by gas
      chromatography coupled to tandem mass spectrometry using a triple quadrupole mass
      analyzer. The target compounds were detected by electron impact with selected
      reaction monitoring, and mass spectrometric conditions were optimized in order to
      increase selectivity and sensitivity. The developed method was validated, and
      matrix-matched calibration was used for quantification purposes. Repeatability
      and interday precision ranged from 0.9% to 16.8% and from 1.6% to 22.3%,
      respectively. Limits of quantification ranged from 0.07 to 2.50 microg kg(-1).
      The proposed method was applied to the analysis of agricultural soil samples
      collected from Almeria (Spain), and PAHs and PCBs were detected in some samples
      at concentrations ranging from 0.1 to 210 microg kg(-1).

PMID- 19760405
TI  - Pristine single-walled carbon nanotube purity evaluation by using (1)H NMR
      spectroscopy.
AB  - Proper purity characterization of single-walled carbon nanotubes (SWCNTs) is an
      increasingly hot topic in the area of carbon nanotechnology. There are
      inconsistencies in purity characterization of SWCNT from manufacturers and in the
      literature. Purity of "as received," oven dried, and NaHCO(3)-washed SWCNTs of
      three commercially available brands (NanoLab, SWeNT, and HiPco) is explored by
      using a consistent methodology via proton nuclear magnetic resonance ((1)H NMR)
      spectroscopy comparison, across three NMR solvents: DMSO-d (6), CDCl(3), and
      D(2)O. Important insights into the purity of commercially available SWCNT and the
      importance of washing (cleaning) samples before use are offered.

PMID- 19760406
TI  - Detection of angiotensin II type 1 receptor ligands by a cell-based assay.
AB  - This work describes a cell-based assay that does not depend on radioactivity or
      laboratory animals for the detection of ligands of angiotensin II type 1 receptor
      (AT1R). The assay makes use of stable transfected Chinese hamster ovary cells
      (CHO-AT1R) expressing the AT1R. A sequential saturation assay principle was used
      in which receptor binding sites of the CHO-AT1R cells are blocked by the analyte
      in a concentration-dependent manner. Afterwards, TAMRA-angiotensin II, a
      fluorescence-labeled ligand, was added to bind to the remaining free binding
      sites of the receptor. In consequence, the fluorescence signal determined is
      inversely proportional to the concentration of the analyte.

PMID- 19760409
TI  - Whole-body dual-energy X-ray absorptiometry.

PMID- 19760408
TI  - Mirror neurons: from discovery to autism.

PMID- 19760410
TI  - A case of relapsing flitting bilateral idiopathic orbital inflammation.
AB  - Idiopathic orbital inflammation (IOI) is defined as a benign non-infective
      clinical syndrome characterized by features of non-specific inflammation of the
      orbit without identifiable local or systemic causes. This can be called orbital
      myositis if the inflammation is predominantly in the orbital muscles. It is a
      diagnosis of exclusion based on clinical, radiological, and if necessary,
      histological findings. The most commons symptoms are swelling, ptosis, proptosis
      and painful eye movements. To our knowledge, this patient is the first with IOI
      to demonstrate relapsing flitting bilateral involvement of several individual
      extra-ocular muscles.

PMID- 19760411
TI  - Treating osteonecrosis with autologous bone marrow cells.

PMID- 19760412
TI  - Quantification of regional myocardial oxygen metabolism in normal pigs using
      positron emission tomography with injectable (15)O-O (2).
AB  - PURPOSE: Although (15)O-O(2) gas inhalation can provide a reliable and accurate
      myocardial metabolic rate for oxygen by PET, the spillover from gas volume in the
      lung distorts the images. Recently, we developed an injectable method in which
      blood takes up (15)O-O(2) from an artificial lung, and this made it possible to
      estimate oxygen metabolism without the inhalation protocol. In the present study,
      we evaluated the effectiveness of the injectable (15)O-O(2) system in porcine
      hearts. METHODS: PET scans were performed after bolus injection and continuous
      infusion of injectable (15)O-O(2) via a shunt between the femoral artery and the
      vein in normal pigs. The injection method was compared to the inhalation method.
      The oxygen extraction fraction (OEF) in the lateral walls of the heart was
      calculated by a compartmental model in view of the spillover and partial volume
      effect. RESULTS: A significant decrease of lung radioactivity in PET images was
      observed compared to the continuous inhalation of (15)O-O(2) gas. Furthermore,
      the injectable (15)O-O(2) system provides a measurement of OEF in lateral walls
      of the heart that is similar to the continuous-inhalation method (0.71 +/- 0.036
      and 0.72 +/- 0.020 for the bolus-injection and continuous-infusion methods,
      respectively). CONCLUSION: These results indicate that injectable (15)O-O(2) has
      the potential to evaluate myocardial oxygen metabolism.

PMID- 19760413
TI  - A dose-effect correlation for radioiodine ablation in differentiated thyroid
      cancer.
AB  - PURPOSE: The aim of this study was to determine the range of absorbed doses
      delivered to thyroid remnants, blood, and red marrow from fixed administrations
      of radioiodine and to ascertain whether the success of ablation is more dependent
      on these absorbed doses than on the administered activity. METHODS: Twenty-three
      patients received 3,000 MBq radioiodine following near-total thyroidectomy. The
      maximum absorbed dose to remnants was calculated from subsequent single photon
      emission tomography scans. Absorbed doses delivered to blood and red marrow were
      calculated from blood samples and from whole-body retention measurements. The
      protein bound iodine (PBI) was also calculated. RESULTS: Maximum absorbed doses
      to thyroid remnants ranged from 7 to 570 Gy. Eighteen of the 23 patients had a
      successful ablation. A significant difference was seen between the absorbed doses
      delivered to thyroid remnants, blood, and red marrow for those patients that had
      a successful ablation compared to those with a failed ablation (p = 0.030, p =
      0.043 and p = 0.048, respectively). The difference between the PBI values
      acquired at day 1 and day 6 were also indicative of response (p = 0.074).
      CONCLUSIONS: A successful ablation is strongly dependent on the absorbed dose to
      the thyroid remnant. Dosimetry-based personalized treatment can prevent both sub
      optimal administrations, which entails further radioiodine therapy, and excessive
      administration of radioactivity, which increases the potential for radiation
      toxicity.

PMID- 19760414
TI  - Intraoperative avidination for radionuclide treatment as a radiotherapy boost in
      breast cancer: results of a phase II study with (90)Y-labeled biotin.
AB  - PURPOSE: External beam radiotherapy (EBRT) after conservative surgery for early
      breast cancer requires 5-7 weeks. For elderly patients and those distant from an
      RT center, attending for EBRT may be difficult or impossible. We investigated
      local toxicity, cosmetic outcomes, and quality of life in a new breast
      irradiation technique-intraoperative avidination for radionuclide therapy (IART)
      in which avidin is administered to the tumor bed and (90)Y-labelled biotin later
      administered intravenously to bind the avidin and provide irradiation. Reduced
      duration EBRT (40 Gy) is given subsequently. METHODS: After surgery, 50 (ten
      patients), 100 (15 patients) or 150 mg (ten patients) of avidin was injected into
      the tumor bed. After 12-24 h, 3.7 GBq (90)Y-biotin (beta source for therapeutic
      effect) plus 185 MBq (111)In-biotin (gamma source for imaging and dosimetry) was
      infused slowly. Whole-body scintigraphy and SPECT/CT images were taken for up to
      30 h. Shortened EBRT started 4 weeks later. Local toxicity was assessed by RTOG
      scale; quality of life was assessed by EORTC QOL-30. RESULTS: Of 35 patients
      recruited (mean age 63 years; range 42-74) 32 received IART plus EBRT. 100 mg
      avidin provided 19.5 +/- 4.0 Gy to the tumor bed and was considered the optimum
      dose. No side-effects of avidin or (90)Y-biotin occurred, with no hematological
      or local toxicity. Local G3 toxicity occurred in 3/32 patients during EBRT. IART
      plus EBRT was well accepted, with good cosmetic outcomes and maintained quality
      of life. CONCLUSIONS: IART plus reduced EBRT can accelerate irradiation after
      conservative breast surgery.

PMID- 19760415
TI  - Recombinant human TSH and ablation of post-surgical thyroid remnants in
      differentiated thyroid cancer: the effect of pre-treatment with furosemide and
      furosemide plus lithium.
AB  - BACKGROUND AND AIM: Recombinant human TSH (rhTSH) can be used for post-surgical
      radioiodine (I-131) thyroid remnants ablation in differentiated thyroid cancer
      (DTC) patients after surgery. Debate exists in literature about the optimal
      amount of I-131 that should be given for obtaining an effective ablation and
      about the role of iodine pool during treatment. Therefore, the aim of the present
      study was to assess whether I-131 ablation during rhTSH stimulus can be improved
      by reducing the circulating iodine pool and by increasing thyroid cell uptake and
      retention of I-131 obtained by administering furosemide and lithium. METHODS: A
      total of 201 consecutive DTC patients were entered in the study: they were
      treated by total thyroidectomy and I-131 therapy during rhTSH stimulus to ablate
      thyroid remnants. Patients were divided into two groups according to the TNM
      stage: group 1 included patients in stage I-II who were treated with a low 30-mCi
      I-131 dose, while group 2 included patients in stage III-IV who were treated by a
      high 100-mCi I-131 dose. Moreover, both groups were further subdivided into three
      subgroups. Subgroup (a) included 45 patients from group 1 and 22 from group 2:
      they were treated with I-131 under rhTSH stimulus, following a short 4-day
      withdrawal of L-thyroxine (LT4). Subgroup (b) included 45 patients from group 1
      and 22 from group 2: they were treated with I-131 under rhTSH stimulus, following
      a short 4-day withdrawal of L-T4, and after furosemide administration (25 mg/day
      orally) during the 3 days before I-131. Subgroup (c) included 45 patients from
      group 1 and 22 from group 2: they were treated with I-131 under rhTSH stimulus,
      following a short 4-day L-T4 withdrawal, and after administration of furosemide
      (25 mg/day orally) during the 3 days prior I-131 and lithium (450 mg/day orally)
      during the 3 days following I-131. Another group (group 3) of 20 patients
      characterized by a very low-risk cancer (unifocal tumor <1.0 cm in diameter,
      without extra-capsular extension, N0) was treated with a 30-mCi I-131 dose under
      rhTSH stimulus without performing the short 4-day L-4 withdrawal: this group was
      taken as the control. Follow-up was performed by neck ultrasonography (US), and
      Tg measurement and I-131 WBS under rhTSH stimulus. RESULTS: Among the patients
      from group 1, those pre-treated with furosemide or with furosemide plus lithium
      showed a better outcome of ablation both in terms of undetectable Tg values
      (97.7% and 95.5 % vs. 79.5%, p < 0.05) and of WBS negativity (97.7% vs. 81.8%, p
      < 0.05) during the rhTSH stimulus. No similar findings were observed in group 2
      patients. Moreover, in patients from group 3 (I-131 30 mCi, without L-T4
      withdrawal), the outcome of ablation was significantly lower in comparison to
      patients from group 1 (I-131 30 mCi, with L-T4 withdrawal) in terms of
      undetectable Tg during the rhTSH stimulus (55.0%, p < 0.001). CONCLUSION: rhTSH
      is highly effective for post-surgical thyroid remnant ablation in low-risk cancer
      patients using the low 30-mCi dose protocol combined with the short 4-day
      withdrawal of L-T4. Moreover, in these patients the pre-treatment with furosemide
      seems to play an important role to further improve the outcome of ablation by
      reducing the iodine pool.

PMID- 19760416
TI  - Intrahepatic cholangiocarcinoma and hepatocellular carcinoma: differential
      diagnosis with contrast-enhanced ultrasound.
AB  - OBJECTIVE: We assessed the usefulness of contrast-enhanced ultrasound (CEUS) in
      the differentiation of intrahepatic cholangiocarcinoma (ICC) and hepatocellular
      carcinoma (HCC). METHODS: The CEUS enhancement patterns of 50 ICCs were
      retrospectively analysed and compared with 50 HCCs. Two readers independently
      reviewed the baseline ultrasound (BUS) and CEUS images and the diagnostic
      performances were evaluated by receiver operating characteristic (ROC) analysis.
      Time-intensity curves (TIC) were plotted for quantification analysis. RESULTS: In
      the arterial phase, peripheral rim-like hyperenhancement, heterogeneous
      hyperenhancement, homogeneous hyperenhancement and heterogeneous hypoenhancement
      were found in 25, 10, 3 and 12 of the ICCs versus 2, 29, 19 and 0 of the HCCs (P
      < 0.001), respectively. The diagnostic performance of both readers in terms of
      the area under the ROC curve (0.745 vs. 0.933 for reader 1, and 0.803 vs. 0.911
      for reader 2), sensitivity (28% vs. 90%, and 44% vs. 82%) and accuracy (64% vs.
      90%, and 71% vs. 90%) improved significantly after CEUS (all P < 0.05). The
      interobserver agreement increased from kappa = 0.575 at BUS to kappa = 0.720
      after CEUS. TICs demonstrated that the intensities of the peripheral and central
      portions of the ICCs were lower than those of HCCs (both P < 0.05). CONCLUSION:
      CEUS improves the diagnostic performance significantly in the differentiation
      between ICC and HCC.

PMID- 19760419
TI  - Cardiac CT: the missing piece of the puzzle.

PMID- 19760420
TI  - Does CT have an additional diagnostic value over ultrasound in the evaluation of
      acute inflammatory neck masses in children?
AB  - OBJECTIVES: We assessed the additional value of contrast-enhanced CT versus US
      for evaluation of acute cervical inflammatory masses and choosing treatment
      strategy. METHODS: We retrospectively reviewed 210 files of paediatric patients
      admitted with an acute inflammatory neck mass from 2005 to 2008 (M:F = 108:102,
      mean age 4.5 years). All patients underwent diagnostic ultrasound and Doppler of
      the neck; CT was performed in 25 patients within 2-72 h. Clinical and
      radiological findings were correlated, and imaging impact on patient management
      was assessed. RESULTS: In the 210 patients, US provided sufficient information in
      184 of 185 (99.5%) patients undergoing only US. In one patient with no
      sonographic evidence of collection, an abscess was drained surgically on the
      point of fluctuation. Fluid collections were drained in 17 patients based on US
      findings; inflammatory processes were managed conservatively in 164. CT provided
      additional information in 4 of 25 patients (16.0%), revealing airways compromise
      in 2 and collections in 2. CONCLUSION: US provided sufficient information about
      the nature, location, and extent of the inflammatory mass in 97.6% of our
      patients, suggesting it should be the main, and generally single, imaging
      technique in these patients. CT should be reserved for patients with an
      aggravating clinical course and suspicion of deep neck infection or airways
      compromise.

PMID- 19760421
TI  - Prospectively ECG-triggered high-pitch spiral acquisition for coronary CT
      angiography using dual source CT: technique and initial experience.
AB  - OBJECTIVE: We evaluated radiation exposure and image quality of a new coronary CT
      angiography protocol, high-pitch spiral acquisition, using dual source CT (DSCT).
      MATERIAL AND METHODS: Coronary CTAwas performed in 25 consecutive patients with a
      stable heart rate of 60 bpm or less after premedication, using 2 x 128 0.6-mm
      sections, 38.4-mm collimation width and 0.28-s rotation time. Tube settings were
      100 kV/320 mAs and 120 kV/400 mAs for patients below and above 100-kg weight,
      respectively. Data acquisition was prospectively ECG-triggered at 60% of the R-R
      interval using a pitch of 3.2 (3.4 for the last 10 patients). Images were
      reconstructed with 75-ms temporal resolution, 0.6-mm slice thickness and 0.3-mm
      increment. Image quality was evaluated using a four-point scale (1 = excellent, 4
      = unevaluable). RESULTS: Mean range of data acquisition was 113 +/- 22 mm, mean
      duration was 268 +/- 23 ms. Of 363 coronary artery segments, 327 had an image
      quality score of 1, and only 2 segments were rated as "unevaluable". Mean dose
      length product (DLP) was 71 +/- 23 mGy cm, mean effective dose was 1.0 +/- 0.3
      mSv (range 0.78-2.1 mSv). For 21 patients with a body weight below 100 kg, mean
      DLP was 63 +/- 5 mGy cm (0.88 +/- 0.07 mSv; range 0.78-0.97 mSv). CONCLUSION:
      Prospectively ECGtriggered high-pitch spiral CT acquisition provides high and
      stable image quality at very low radiation dose.

PMID- 19760422
TI  - The role of mean diffusivity (MD) as a predictive index of the response to
      chemotherapy in locally advanced breast cancer: a preliminary study.
AB  - OBJECTIVE: To evaluate the role of mean diffusivity (MD) as a predictive index of
      the response to chemotherapy in locally advanced breast cancer. METHODS: Twenty
      one women referred to our institution with a diagnosis of locally advanced breast
      cancer underwent magnetic resonance imaging (MRI) studies at 1.5 T before
      beginning and after completing combined neoadjuvant chemotherapy. The examination
      protocol included an EPI sequence sensitised to diffusion (b-value 1,000 s/mm(2))
      and three-dimensional (3D) coronal T1 sequences before and after intravenous
      contrast medium. Tumours were delineated by using dynamic MR acquisition before
      and after chemotherapy. The percentage of tumour volume reduction (PVR) and pre
      (MD(pre)) and post-therapy (MD(post)) MD values were computed for each lesion.
      RESULTS: PVR >or= 65% was observed in 17/21 patients (responders). MD(pre) of
      responders (0.99 +/- 0.27 10(-3) mm(2)/s) was significantly (p = 0.025) lower
      than MD(pre) of non-responders (1.46 +/- 0.33 10(-3) mm(2)/s). Moreover, in
      patients as a whole PVR significantly correlated (p = 0.01, r = -0.54) with
      MD(pre). MD(post) (1.26 +/- 0.39 10(-3) mm(2)/s) of responders was
      significantly(p = 0.024) higher than MD(pre) (0.99 +/- 0.27 mm(2) 10(-3)
      mm(2)/s), whereas non-responders MD(post) (1.00 +/- 0.14 10(-3) mm(2)/s)did not
      increase compared with MD(pre) (1.46 +/- 0.33 10(-3) mm(2)/s). CONCLUSIONS: This
      preliminary study seems to indicate that low values of pre-chemotherapy MD may
      identify, before starting treatment, the patients with higher probability of
      response in terms of percentage of volume reduction of the lesion. MD may
      represent a complementary parameter useful to correctly select patients for
      neoadjuvant chemotherapy.

PMID- 19760424
TI  - [Interstitial lung disease in collagen vascular diseases. Diagnostic and
      therapeutic implications of non-specific interstitial pneumonia].
AB  - Interstitial lung disease (ILD) is among the most common organ manifestations in
      collagen vascular diseases and can be a major determinant of the long-term
      prognosis. Early diagnosis rests mainly on spirometry, including measurement of
      the CO diffusion capacity, and high-resolution computed tomography (HRCT). The
      most common histopathology of ILD in collagen vascular diseases is the non
      specific interstitial pneumonia (NSIP) pattern. It is distinguished from the
      usual interstitial pneumonia (UIP) pattern, which is most common in idiopathic
      lung fibrosis, by a significant inflammatory component, a distinct HRCT pattern,
      with often prominent ground-glass opacities, and a distinct cell pattern on
      bronchoalveolar lavage (BAL) with an often prominent lymphocyte component.
      Therapeutic experience is heterogeneous but evidence is accumulating suggesting
      that NSIP in the collagen vascular diseases is amenable to immunosuppression.
      Rapid clinical and/or radiological deterioration, reflecting inflammatory
      activity, appears to mark those patients who are most likely to benefit from
      cyclophosphamide therapy.

PMID- 19760425
TI  - [Histomorphology of interstitial lung disease and pulmonary vasculitis].
AB  - Rheumatic diseases or collagen vascular diseases represent a heterogeneous group
      of immunologically mediated inflammatory disorders. The respiratory system is
      often affected,the causes being manifold: infection, medication toxicity and
      specific manifestations of immunological processes due to the underlying disease.
      The lung can be involved in all its components. Due to their extremely broad
      differential diagnosis, pulmonary vasculitic syndromes still constitute a major
      challenge for the pathologist. Pulmonary involvement is frequent in primary
      systemic vasculitis (PSV) associated with anti-neutrophil-cytoplasmic antibodies
      (ANCA); other PSV only rarely affect the lungs. Histomorphologically, small
      vessel vasculitis with neutrophil alveolitis and diffuse alveolar hemorrhage, as
      well as extravascular intraparenchymal or peribronchial granulomas, can point to
      PSV. A single biopsy is often insufficient to identify all diagnostic criteria.
      Therefore, the selection of suitable biopsy material and correlation with
      clinical, serological and radiological parameters is indispensable. Almost all
      forms of interstitial lung disease may be present in collagen vascular disease;
      however, several parallel morphological types, rather than one in isolation, are
      frequently found.

PMID- 19760426
TI  - [Interstitial lung disease].
AB  - Vasculitis and connective tissue disease are often associated with interstitial
      lung disease. Involvement of lung parenchyma is found in small vessel vasculitis
      and mostly in ANCA-associated forms such as Wegener's granulomatosis. In addition
      to vasculitis and connective tissue disease, rheumatoid arthritis can lead to
      interstitial lung disease and lung fibrosis. Diagnostic tools include measurement
      of auto-antibodies, lung function test, chest X-rays and computed tomography of
      the thorax, as well as bronchoscopy with biopsy and bronchoalveolar lavage. The
      following article provides an overview of the clinical, histological and
      radiologic patterns of interstitial lung disease in vasculitis, rheumatoid
      arthritis and connective tissue disease. Treatment options will also be
      discussed.

PMID- 19760427
TI  - Spontaneous and radiation-induced chromosomal instability and persistence of
      chromosome aberrations after radiotherapy in lymphocytes from prostate cancer
      patients.
AB  - The aim of the study was to compare the spontaneous and ex vivo radiation-induced
      chromosomal damage in lymphocytes of untreated prostate cancer patients and age
      matched healthy donors, and to evaluate the chromosomal damage, induced by
      radiotherapy, and its persistence. Blood samples from 102 prostate cancer
      patients were obtained before radiotherapy to investigate the excess acentric
      fragments and dicentric chromosomes. In addition, in a subgroup of ten patients,
      simple exchanges in chromosomes 2 and 4 were evaluated by fluorescent in situ
      hybridization (FISH), before the onset of therapy, in the middle and at the end
      of therapy, and 1 year later. Data were compared to blood samples from ten age
      matched healthy donors. We found that spontaneous yields of acentric chromosome
      fragments and simple exchanges were significantly increased in lymphocytes of
      patients before onset of therapy, indicating chromosomal instability in these
      patients. Ex vivo radiation-induced aberrations were not significantly increased,
      indicating proficient repair of radiation-induced DNA double-strand breaks in
      lymphocytes of these patients. As expected, the yields of dicentric and acentric
      chromosomes, and the partial yields of simple exchanges, were increased after the
      onset of therapy. Surprisingly, yields after 1 year were comparable to those
      directly after radiotherapy, indicating persistence of chromosomal instability
      over this time. Our results indicate that prostate cancer patients are
      characterized by increased spontaneous chromosomal instability. This instability
      seems to result from defects other than a deficient repair of radiation-induced
      DNA double-strand breaks. Radiotherapy-induced chromosomal damage persists 1 year
      after treatment.

PMID- 19760428
TI  - Postmortem biochemistry and immunohistochemistry of chromogranin A as a stress
      marker with special regard to fatal hypothermia and hyperthermia.
AB  - Chromoganin A (CgA) is widely distributed in the secretory granules of endocrine
      and neuroendocrine cells and cosecreted with hormones such as catecholamines. The
      present study investigated postmortem serum and cerebrospinal fluid (CSF) levels
      of CgA in comparison with those of catecholamines, and also cellular CgA
      immunopositivity in the hypothalamus, adenohypophysis and adrenal medulla to
      assess forensic pathological significance. Serial medicolegal autopsy cases (n =
      298, within 3 days postmortem) were used. Serum and CSF CgA levels were
      independent of the gender or age of subjects or postmortem time. The most
      characteristic findings were seen for fatal hypothermia (cold exposure),
      hyperthermia (heat stroke) and intoxication. Serum CgA levels were lower for
      hypothermia and intoxication than for other causes of death (p < 0.05), while CSF
      CgA levels were higher for hypothermia (p < 0.0001). A negative correlation was
      detected between serum and CSF CgA levels for hypothermia (R = 0.552, p < 0.05).
      Correlations between serum levels of CgA and catecholamines (adrenaline,
      noradrenaline and dopamine) were evident for hyperthermia (R = 0.632-0.757, p <
      0.05 to <0.01), but there was no significant correlation between CgA and
      catecholamine levels in CSF. Cellular CgA immunopositivity in the hypothalamus,
      adenohypophysis and adrenal medulla varied extensively among cases in each group.
      However, CgA immunopositivity in hypothalamus neurons was lower for hypothermia
      than other causes of death including hyperthermia and intoxication. These
      observations suggest characteristic neuroendocrinal activation in fatal cases of
      hypo- and hyperthermia and also intoxication. CgA may be a useful biochemical and
      immunohistochemical marker for investigating these causes of death.

PMID- 19760429
TI  - Hypothesis on the pathogenesis of retinopathy of prematurity--it is not VEGF
      alone but anatomical structures that are crucial.

PMID- 19760430
TI  - Superior oblique tucking with versus without additional inferior oblique
      recession for acquired trochlear nerve palsy.
AB  - BACKGROUND: Inferior oblique recession (IOR), superior oblique tucking or
      advancement (SOT) and a combination of both (SOT&IOR) are most popular as
      treatments for acquired trochlear nerve (N.IV) palsy. Recently, it has been
      reported that results of a modified SOT technique and SOT&IOR were nearly
      equivalent. We investigated the effects of SOT and SOT&IOR in 37 patients with
      unilateral acquired isolated N.IV palsy. METHODS: Retrospective study of patients
      with unilateral acquired N.IV palsy who were operated at the University Hospitals
      of Giessen (1996 to 2007) and Essen (2003 to 2007). Examinations with Harms'
      tangent scale (2.5 m, dark red glass in front of non-paretic eye) were performed
      before and 3 months after pure SOT or SOT + IOR. When the palsy was on OS, squint
      angles were transformed corresponding to palsy on OD. MAIN OUTCOME MEASURES:
      horizontal, vertical and cyclotorsional deviations in nine diagnostic gaze
      directions and the field of binocular fusion. RESULTS: In total, it was possible
      to examine 37 patients 3 months post surgery: 16 had received pure SOT, and 21
      SOT&IOR. Preoperative deviations did not differ significantly between the pure
      SOT and SOT&IOR groups. Dosage was 6 to 8 mm for pure SOT (median, 8) and 8 to 18
      mm (median, 11) for SOT&IOR (with 4 to 8 mm SOT). At 3 months, elevation
      deficiency in adduction was less severe with pure SOT compared to SOT&IOR, but at
      the same time the effect on the vertical deviation was less pronounced.
      CONCLUSION: Additional IOR augments the effect of SOT, but also its side-effects,
      i.e. consecutive Brown's syndrome.

PMID- 19760431
TI  - The effects of low-intensity resistance training with vascular restriction on leg
      muscle strength in older men.
AB  - The purpose of this study was to investigate and compare the effects of two types
      of resistance training protocols on the adaptation of skeletal muscle strength in
      older men. Thirty-seven healthy male subjects (50-64 years) participated in this
      study. Subjects were assigned to one of three groups: high-intensity (80% 1-RM)
      resistance training (RT80); low-intensity (20% 1-RM) resistance training with
      vascular restriction (VR-RT20); and a control group (CON) that performed no
      exercise. Subjects in both exercise groups performed three upper body (at 80% 1
      RM) and two lower body exercises either with (20% 1-RM) or without (80% 1-RM)
      vascular restriction three times a week for 6 weeks. As expected, the RT80 and VR
      RT20 groups had significantly (p < 0.01) greater strength increases in all upper
      body and leg press exercises compared with CON, however, absolute strength gains
      for the RT80 and VR-RT20 groups were similar (p > 0.05). It should be noted that
      the percentage increase in leg extension strength for the RT80 group was
      significantly greater than that for both the VR-RT20 (p < 0.05) and CON groups (p
      < 0.01), while the percentage increase in leg extension strength for the VR-RT20
      group was significantly (p < 0.01) greater than that for the CON. The findings
      suggested that leg muscle strength improves with the low-load vascular
      restriction training and the VR-RT20 training protocol was almost as effective as
      the RT80 training protocol for increasing muscular strength in older men.

PMID- 19760432
TI  - Ischemic preconditioning improves maximal performance in humans.
AB  - Repeated episodes of ischemia followed by reperfusion, commonly referred to as
      ischemic preconditioning (IPC), represent an endogenous protective mechanism that
      delays cell injury. IPC also increases blood flow and improves endothelial
      function. We hypothesize that IPC will improve physical exercise performance and
      maximal oxygen consumption. The purpose of the study was to examine the effect of
      ischemic preconditioning in leg skeletal muscles on cycling exercise performance
      in healthy individuals. Fifteen healthy, well-trained subjects performed two
      incremental maximal exercise tests on a bicycle ergometer. Power output, oxygen
      consumption, ventilation, respiratory quotient, and heart rate were measured
      continuously. Blood pressure and blood lactate were measured before and after the
      test. One exercise test was performed after the application of ischemic
      preconditioning, using a protocol of three series of 5-min ischemia at both legs
      with resting periods of 5 min in between. The other maximal cycling test served
      as a control. Tests were conducted in counterbalanced order, at least 1 week
      apart, at the same time of the day. The repeated ischemic periods significantly
      increased maximal oxygen consumption from 56.8 to 58.4 ml/min per kg (P = 0.003).
      Maximal power output increased significantly from 366 to 372 W (P = 0.05).
      Ischemic preconditioning had no effect on ventilation, respiratory quotient,
      maximal heart rate, blood pressure or on blood lactate. Repeated short-term leg
      ischemia prior to an incremental bicycle exercise test improves maximal oxygen
      consumption by 3% and power output by 1.6%. This protocol, which is suggested to
      mimic the effects of ischemic preconditioning, may have important implications
      for exercise performance.

PMID- 19760433
TI  - Intra- and interobserver reproducibility of interpretation of immunohistochemical
      stains of prostate cancer.
AB  - The evaluation of immunohistochemistry (IHC) is usually semiquantitative, and
      thus subject to observer variability. We analyzed the reproducibility of
      different IHC measures. Fifty TMA cores of prostate cancer were stained for PDX
      1, a transcription factor overexpressed in the cytoplasm of prostate cancer
      cells. The strongest intensity was scored 0-3 and 1-3 was used for extent (1-33%,
      34-66%, and 67-100%). The stains were evaluated twice by four observers: two
      genitourinary pathologists, and two medical doctors with no formal pathology
      training. Staining intensity was also measured with automated image analysis. The
      pathologists read the slides faster than nonpathologists (total time 88 and 178
      min, respectively, p = 0.03). Mean weighted kappa for intraobserver agreement was
      0.85 (range 0.81-0.89) for intensity and 0.43 (range 0.38-0.51) for extent with
      similar results among pathologists and nonpathologists. Mean weighted kappa for
      interobserver agreement was 0.80 (range 0.77-0.84) for intensity and 0.21 (range
      0.11-0.26) for extent. The subjective estimations of intensity correlated with
      results of image analysis (r = 0.61-0.66, p < 0.001), but the correlation between
      observers was stronger (r = 0.75-0.81) and correlated better with Gleason grade.
      Thus, subjective assessment of intensity can be done with a high level of
      reproducibility while estimation of staining extent is less reliable. Although
      educated pathologists were faster, the level of pathology training is not crucial
      for obtaining reproducible results in the analysis of TMA-based studies.

PMID- 19760434
TI  - Athletics, minor trauma, and pediatric arterial ischemic stroke.
AB  - Pediatric arterial ischemic stroke may occur as the result of trivial head or
      neck trauma sustained during a sports activity. We describe three cases of sports
      related stroke in previously healthy school-age children and discuss acute and
      long-term stroke care. Possible mechanisms of sports-related stroke are
      addressed, as is evaluation for cause of stroke in children. In one of the
      reported cases, the child was found to have a vertebral artery dissection as the
      cause of his stroke, but no definitive cause of stroke was identified in the
      other two cases despite extensive evaluation. The advisability and timing of
      returning to athletic activities after stroke is also discussed. Many children
      with sports-related stroke are initially seen by a sports trainer, a
      pediatrician, or an ER physician. Thus, it is particularly important that these
      professionals are aware of the possibility of ischemic stroke occurring after
      even mild athletic injury. Childhood stroke may result from injuries sustained
      during athletic activities and should be considered when a child has acute focal
      neurologic signs.

PMID- 19760435
TI  - Evaluation of larvicidal nature of fleshy fruit wall of Momordica charantia Linn.
      (family: cucurbitaceae) in the management of mosquitoes.
AB  - In view of the recently increased interest in developing plant-based insecticides
      as an alternative to chemical insecticides, this study was undertaken to assess
      the larvicidal potential of the various fruit wall extracts of Momordica
      charantia (cucurbitaceae) against two species of mosquito vectors, Anophels
      stephensi and Culex quinquefasciatus. Among the extracts tested, petroleum ether
      (LC(50) = 27.60; 17.22 ppm and 41.36; 15.62 ppm) extract was found more effective
      than carbon tetrachloride (LC(50) = 49.58; 16.15 ppm and 80.61; 27.64 ppm) and
      methanol (LC(50) = 142.82; 95.98 ppm and 1,057.49; 579.93 ppm) extracts towards
      anopheline and culicine larvae after 24 and 48 h of exposure respectively. Thus,
      all fruit wall extracts of M. charantia are toxic to both the larval species. M.
      charantia may, therefore, act as an effective biolarvicide against mosquitoes in
      the future.

PMID- 19760436
TI  - Engrained experience--a comparison of microclimate perception schemata and
      microclimate measurements in Dutch urban squares.
AB  - Acceptance of public spaces is often guided by perceptual schemata. Such schemata
      also seem to play a role in thermal comfort and microclimate experience. For
      climate-responsive design with a focus on thermal comfort it is important to
      acquire knowledge about these schemata. For this purpose, perceived and "real"
      microclimate situations were compared for three Dutch urban squares. People were
      asked about their long-term microclimate perceptions, which resulted in
      "cognitive microclimate maps". These were compared with mapped microclimate data
      from measurements representing the common microclimate when people stay outdoors.
      The comparison revealed some unexpected low matches; people clearly overestimated
      the influence of the wind. Therefore, a second assumption was developed: that it
      is the more salient wind situations that become engrained in people's memory. A
      comparison using measurement data from windy days shows better matches. This
      suggests that these more salient situations play a role in the microclimate
      schemata that people develop about urban places. The consequences from this study
      for urban design are twofold. Firstly, urban design should address not only the
      "real" problems, but, more prominently, the "perceived" problems. Secondly,
      microclimate simulations addressing thermal comfort issues in urban spaces should
      focus on these perceived, salient situations.

PMID- 19760437
TI  - Previous vertebral compression fractures add to the deterioration of the
      disability and quality of life after an acute compression fracture.
AB  - Prevalent vertebral compression fracture(s) have been reported as having a
      negative impact on pain, disability, and quality of life. But no study has
      evaluated the effect of previous fracture on the course of acute compression
      fractures. The aim of the present study was to compare the natural course of the
      acute compression fracture in patients with (n = 51) and without (n = 56)
      previous vertebral compression fracture(s). The study is a retrospective analysis
      of a prospective cohort followed with postal questionnaires during a 12-month
      period after an acute fracture event. Eligible patients were those over 40 years
      of age, who were admitted to the emergency unit because of back pain and had an X
      ray confirmed acute vertebral body fracture. A total of 107 patients were
      included in the study. The pain, disability (von Korff pain and disability
      scores), ADL (Hannover ADL score), and quality of life (QoL) (EQ-5D) were
      measured after 3 weeks, and 3, 6, and 12 months. The X-rays from the first visit
      to the emergency unit were evaluated. The difference of the scores between the
      groups with and without previous fracture was statistically significant (P <
      0.05) at 3 weeks, 6 and 12 months for von Korff disability score, at all
      occasions for EQ-5D and at 3-12 months for Hannover ADL score, but only at 12
      months for the von Korff pain intensity score. In both the groups all scores had
      improved in a statistically significant way at 3 months. The number of previous
      fractures was related to all the outcome scores in a statistically significant
      way (P < 0.05) except von Korff pain intensity score at 3 weeks and 3 months and
      von Korff disability score at 3 months. In conclusion, disability, ADL, and QoL
      scores, but not pain intensity score, were significantly worse in the patients
      with previous fracture from the fracture episode through the first 12 months.
      However, the improvements during the follow-up year seen in both groups were of a
      similar magnitude. The presence or absence of a previous fracture in an acutely
      fractured patient will influence the prognosis and thus possibly also the
      indications for treatments.

PMID- 19760438
TI  - Excited state intramolecular proton transfer in 3-hydroxy flavone and 5-hydroxy
      flavone: a DFT based comparative study.
AB  - Potential energy (PE) curves for the intramolecular proton transfer in the ground
      (GSIPT) and excited (ESIPT) states of 3-hydroxy-flavone (3HF) and 5-hydroxy
      flavone (5HF) were studied using DFT/B3LYP (6-31G (d,p)) and TD-DFT/B3LYP (6-31G
      (d,p)) level of theory respectively. Our calculations suggest the non-viability
      of ground state intramolecular proton transfer for both the compounds. Calculated
      PE curves of 3HF for the ground and excited singlet states proton transfer
      process explain its four state laser diagram. Excited states PE calculations
      support the ESIPT process to both 5HF and 3HF. The difference in ESIPT emission
      process of 3HF and 5HF have been explained in terms of HOMO and LUMO electron
      distribution of the enol and keto tautomer of these two compounds.

PMID- 19760439
TI  - Surgical nuances of giant paraclinoid aneurysms.
AB  - Paraclinoid aneurysms constitute formidable surgical challenge. The complex
      surgical anatomy and several factors such as size and projection of the lesion,
      choice of the surgical approach, relationships between the aneurysm and
      perforator vessels, site of proximal control, and potential improvement or
      worsening of visual symptoms account for these difficulties. In such complex
      cases, surgical nuances frequently determine the final outcome. In this paper,
      the authors present a comprehensive review of the tricky regional anatomy and
      describe the operative nuances one of the senior authors (E. dO.) has used to
      operate on these complex lesions.

PMID- 19760440
TI  - Granular medium impacted by a projectile: experiment and model.
AB  - We present a minimal discrete model for the propagation of energy through a 3D
      granular medium impacted by a particulate projectile. In this model, energy is
      transferred from grain to grain via binary collision events. This description can
      be successfully applied to the analysis of the collision process of a single
      spherical particle (of diameter donto a half space of granular medium composed of
      similarly sized particles. The model reproduces remarkably well the experimental
      observations. Besides, the present model provides a clear picture of the
      mechanism of energy propagation. A continuum version of the model, where the
      energy propagation from bead to bead is characterized by a diffusion equation, is
      derived. The diffusion coefficient is found to be proportional to the ratio of
      d(2) to the characteristic collision time Tau(c) . The numerical value of the
      coefficient of proportionality is essentially governed by the geometry of the
      packing. This paper constitutes an extension of a previously published letter (J.
      Crassous, D. Beladjine, A. Valance, Phys. Rev. Lett. 99, 248001 (2007)).

PMID- 19760441
TI  - Biotechnological strains of Komagataella (Pichia) pastoris are Komagataella
      phaffii as determined from multigene sequence analysis.
AB  - Pichia pastoris was reassigned earlier to the genus Komagataella following
      phylogenetic analysis of gene sequences. Since that time, two additional species
      of Komagataella have been described, K. pseudopastoris and K. phaffii. Because
      these three species are unlikely to be resolved from the standard fermentation
      and growth tests used in yeast taxonomy, the identity of biotechnologically
      important strains of K. pastoris was determined from multigene sequence analyses.
      Results from this study show that the strain of 'Pichia pastoris' commonly used
      in gene expression studies is actually K. phaffii.

PMID- 19760442
TI  - Prevalence and associated risk factors of sleep-disordered breathing symptoms in
      young and middle-aged Pakistani employed adults.
AB  - PURPOSE: The objective of this study was to evaluate the prevalence of self
      reported sleep-disordered breathing (SDB symptoms and its associated risk factors
      in Pakistani employed adults. METHODS: Full-time employees (n = 3470) of a
      medical university were evaluated. Self-administered questionnaire elicited
      information about demographic data, symptoms of SDB, smoking and alcohol use,
      presence of nasal congestion, family history of snoring, and included the Epworth
      Sleepiness Scale. Prevalence of self-reported snoring and of combined SDB
      symptoms (snoring plus at least one other SDB symptom) was evaluated. Regression
      analyses were used to assess risk factors associated with self-reported snoring
      and combined SDB symptoms. RESULTS: Among the 2,497 (72%) responders, prevalence
      of self-reported snoring was 32%, and combined SDB symptoms 25%. A higher
      prevalence of snoring and combined SDB symptoms in male gender diminished with
      age. In univariate analysis, the odds of snoring was higher with age >or=35 yrs
      (odds ratio (OR) 2.6, confidence interval (CI) 2.2-3.2), body mass index >or=23
      (OR 2.6, CI 2.2-3.1), and collar size above 40 cm (OR 2.7, CI 2.3-3.3). Self
      reported nasal blockage (OR 1.9, CI 1.6-2.2) and family history of snoring (OR
      2.9, 2.5-3.5) were other risk factors. In logistic regression analysis,
      significant risk factors for SDB symptoms were age, body mass index, collar size,
      nasal blockage, and family history of snoring. Male gender, smoking and alcohol
      were not significant risk factors for SDB symptoms. CONCLUSION: The prevalence of
      SDB symptoms in Pakistani employed adults was comparable to Western populations.
      However, male gender and smoking were not significant risk factors for SDB
      symptoms.

PMID- 19760443
TI  - Phytotechnologies to promote sustainable land use and improve food safety:
      outcomes and outlook from the European COST Action 859. Preface.

PMID- 19760444
TI  - Partitioning of fluorotelomer alcohols (FTOH) to semipermeable membrane devices
      (SPMD).
AB  - BACKGROUND, AIM, AND SCOPE: Fluorotelomer alcohols (FTOH) are widely used
      substances that were detected even in remote regions of the world. For the
      determination of FTOH in the atmosphere, appropriate sampling techniques are
      needed. In this study, triolein-filled low-density polyethylene tubes were used
      as semipermeable membrane devices (SPMD) and tested for their suitability as
      passive air samplers for FTOH. MATERIALS AND METHODS: Partitioning to and from
      SPMD were investigated for four FTOH of different chain length and concentration
      levels in laboratory and field experiments. FTOH were extracted by liquid-liquid
      extraction with acetonitrile:n-hexane 1:1 and determined by gas chromatography
      (GC)-positive ion chemical ionisation mass spectrometry (MS). RESULTS: FTOH
      behaved differently depending on applied concentrations. At high FTOH levels,
      compound passage through the membrane and uptake appeared to be best for 6:2
      FTOH, but passage of long-chain FTOH was in the same order of magnitude. At low
      FTOH concentration levels, mass transfer and uptake was best for short-chain
      FTOH. Partitioning of 4:2 FTOH to SPMD exceeded partitioning of 10:2 FTOH by
      nearly two orders of magnitude. DISCUSSION: FTOH partitioning to SPMD seems to be
      dependent on the fluorinated chain length and controlled by the SPMD membrane
      acting as a barrier. Migration of long-chain FTOH through the membrane was
      hampered, probably due to the oleophobic properties of the fluorinated alkyl
      chain. Because of the constricted diffusion of FTOH through the SPMD membrane at
      low FTOH levels, an adequate accumulation in the passive sampler is prevented.
      Thus, sensitivity of the analytical method in combination with the enrichment of
      FTOH in SPMD was not sufficient to achieve adequate method detection limit at low
      FTOH levels. CONCLUSIONS: Application of SPMD as passive air samplers for FTOH
      did not seem to be a suitable method for environmentally relevant FTOH
      concentrations. RECOMMENDATIONS AND PERSPECTIVES: As a consequence, we can only
      recommend the use of SPMD for FTOH of presumably high contamination levels.

PMID- 19760445
TI  - Different ratios of docosahexaenoic and eicosapentaenoic acids do not alter
      growth, nucleic acid and fatty acids of juvenile cobia (Rachycentron canadum).
AB  - An experiment was performed to study the effect of different ratios of
      docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on the growth, nucleic
      acid and fatty acids of cobia (Rachycentron canadum) juveniles. The juveniles
      were fed for 8 weeks using seven treatment diets (D-1-D-7) with the same amount
      of DHA and EPA (1.50 +/- 0.1% of dried diet), but varying ratios of DHA to EPA
      (0.90, 1.10, 1.30, 1.50, 1.70, 1.90, 2.10, respectively) and a control diet (D-0,
      DHA + EPA = 0.8% of dried diet, DHA/EPA = 1.30). At the end of the experiment,
      the mean body weight (BW) of juveniles fed D-0-D-7 increased significantly (from
      6.86 +/- 1.64 in the week 0 to 58.52 +/- 16.45 g at the end of week 8, P < 0.05).
      The mean RNA amount and RNA/DNA ratio in the muscle (from 39.62 +/- 1.30 microg
      mg(-1) and 2.29 +/- 0.11 in the week 0 to 272.55 +/- 10.70 microg mg(-1) and
      14.54 +/- 1.75 at the end of week 8, respectively) and the mean weight in the
      liver (from 117.70 +/- 11.15 microg mg(-1) and 3.14 +/- 0.25 in the week 0 to
      793.07 +/- 13.38 microg mg(-1) and 13.16 +/- 0.76 at the end of week 8,
      respectively) of cobia juveniles fed D-0-D-7 were significantly higher at the end
      of 8-week experiment than initially (P < 0.05). The RNA/DNA ratio in the muscle
      and liver of cobia juveniles increased with their growth and appeared an obvious
      positive relationship, especially in the muscle, based on regression analysis.
      The mean lipid content increased significantly in the liver (from 29.82 +/- 0.99
      to 37.47 +/- 3.25% totally) and muscle (from 6.74 +/- 0.25 to 10.63 +/- 0.23%
      totally) of cobia juveniles (P < 0.05). However, no significant difference was
      found on the lipid contents of juveniles fed different diets for 8 weeks (P >
      0.05). In the muscle and liver of juveniles, EPA decreased with its reduction in
      the diet; DHA, DHA/EPA ratio and poly unsaturated fatty acids (PUFAs) generally
      increased with their increment in the diet. The conclusion was drawn that the
      growth, nucleic acid and fatty acids of cobia juveniles were not significantly
      affected by different DHA/EPA ratios in our experiments.

PMID- 19760446
TI  - Formal proof that the split genes of tRNAs of Nanoarchaeum equitans are an
      ancestral character.
AB  - A proof is given that the genes of the tRNA molecule of Nanoarchaeum equitans
      split into the 5' and 3' halves are an ancestral trait. First, the existence of a
      natural succession of evolutionary stages will be proven, formed in the order of
      the three gene structures of tRNAs known today: (i) the split genes of tRNAs,
      (ii) the genes of tRNAs with introns, and (iii) the genes of tRNAs continuously
      codifying for the tRNA molecule. This succession of evolutionary stages
      identifies the split genes of tRNAs as a pleisiomorphic character. The proof that
      this succession of evolutionary stages is, moreover, true is performed by proving
      that all the possible remaining five successions of evolutionary stages are
      false. Indeed, the succession of evolutionary stages considering split genes as a
      derived character turns out to be false in that the increase in complexity
      inherent to this succession cannot be justified by the split genes of tRNAs
      because these could not have conferred any selective advantage justifying this
      increase in complexity. Furthermore, genetic drift is unable to explain the
      evolution of split genes of tRNAs because of the enormous genetic effective size
      of the population observed in these organisms. The remaining four successions of
      evolutionary stages are also false because: (i) they are not natural successions
      of evolutionary stages, (ii) the absolute observed frequencies of these
      evolutionary stages are such as to exclude categorically that they might be
      natural successions of evolutionary stages, and also (iii) two of these are
      falsified by the fact that they do not place the evolutionary stage of genes of
      tRNAs with introns in a close evolutionary relationship with that of the split
      genes of tRNAs which can, instead, be proven to have a close evolutionary link.
      Therefore, there remains only the succession of evolutionary stages considering
      the split genes of tRNAs codifying for the 5' and 3' halves, as a pleisiomorphic
      character, as the only succession compatible with all the arguments presented in
      this article and as the one that actually operated during the evolution of the
      tRNA molecule. This proof has two very important implications. One regards how
      the tRNA molecule originated; considering how tRNA originated as the union of two
      hairpin-like structures, the split genes of tRNAs might be the transition stage
      through which the evolution of this molecule passed. The other regards when the
      genes of tRNAs originated, reaching the conclusion that the origin of these genes
      is polyphyletic, i.e. not monophyletic and hence contrary to the assumptions of
      the current paradigm.

PMID- 19760447
TI  - Phylogenetic analysis of the NEEP21/calcyon/P19 family of endocytic proteins:
      evidence for functional evolution in the vertebrate CNS.
AB  - Endocytosis and vesicle trafficking are required for optimal neural transmission.
      Yet, little is currently known about the evolution of neuronal proteins
      regulating these processes. Here, we report the first phylogenetic study of
      NEEP21, calcyon, and P19, a family of neuronal proteins implicated in synaptic
      receptor endocytosis and recycling, as well as in membrane protein trafficking in
      the somatodendritic and axonal compartments of differentiated neurons. Database
      searches identified orthologs for P19 and NEEP21 in bony fish, but not
      urochordate or invertebrate phyla. Calcyon orthologs were only retrieved from
      mammalian databases and distant relatives from teleost fish. In situ localization
      of the P19 zebrafish ortholog, and extant progenitor of the gene family, revealed
      a CNS specific expression pattern. Based on non-synonymous nucleotide
      substitution rates, the calcyon genes appear to be under less intense negative
      selective pressure. Indeed, a functional group II WW domain binding motif was
      detected in primate and human calcyon, but not in non-primate orthologs.
      Sequencing of the calcyon gene from 80 human subjects revealed a non-synonymous
      single nucleotide polymorphism that abrogated group II WW domain protein binding.
      Altogether, our data indicate the NEEP21/calcyon/P19 gene family emerged, and
      underwent two rounds of gene duplication relatively late in metazoan evolution
      (but early in vertebrate evolution at the latest). As functional studies suggest
      NEEP21 and calcyon play related, but distinct roles in regulating vesicle
      trafficking at synapses, and in neurons in general, we propose the family arose
      in chordates to support a more diverse range of synaptic and behavioral
      responses.

PMID- 19760448
TI  - Seasonal and episodic lake mixing stimulate differential planktonic bacterial
      dynamics.
AB  - Yuan Yang Lake (YYL), Taiwan, experiences both winter and typhoon-initiated
      mixing, and each type of mixing event is characterized by contrasting
      environmental conditions. Previous work suggested that after typhoon mixing,
      bacterial communities in YYL reset to a pioneer composition and then follow a
      predictable trajectory of change until the next typhoon. Our goal was to continue
      this investigation by observing bacterial community change after a range of
      mixing intensities, including seasonal winter mixing. We fingerprinted aquatic
      bacterial communities in the epilimnion and hypolimnion using automated ribosomal
      intergenic spacer analysis and then assessed community response using
      multivariate statistics. We found a significant linear relationship between water
      column stability and the epilimnion to hypolimnion divergences. In comparison to
      the summer, we found the winter community had a distinct composition and less
      variation. We divided the bacterial community into population subsets according
      to abundance (rare, common, or dominant) and occurrence (transient or persistent)
      and further explored the contribution of these subsets to the overall community
      patterns. We found that transient taxa did not drive bacterial community patterns
      following weak typhoon mixing events, but contributed substantially to patterns
      observed following strong events. Common taxa generally did not follow the
      community trajectory after weak or strong events. Our results suggest intensity,
      frequency, and seasonality jointly contribute to aquatic bacterial response to
      mixing disturbance.

PMID- 19760449
TI  - Transitional cell carcinoma in urachal cyst.
AB  - A 33-year-old male patient with abdominal mass for a year was referred to our
      institute. CT scan with intravenous contrast was performed, which showed a cystic
      lesion at the infraumbilical region, beneath the anterior abdominal wall with the
      presence of solid enhancing mass apposed to the anterior wall of the cyst. We
      suggested a diagnosis of urachal cyst with possibility of malignancy. On surgical
      exploration, the cystic mass was found superior to and separate from the urinary
      bladder dome. Histopathology revealed transitional cell carcinoma in a urachal
      cyst.

PMID- 19760450
TI  - Adnexal torsion: color Doppler and three-dimensional ultrasound.
AB  - OBJECTIVE: To correlate preoperative ultrasound and color Doppler findings in
      patients with surgically proven adnexal torsion. MATERIALS AND METHODS: A 5-year
      retrospective study included 36 patients with acute lower abdominal and/or pelvic
      pain. Twenty-four patients had complete adnexal torsion followed by adnexectomy.
      Twelve patients with partially twisted adnexa underwent detorsion and were
      followed by 3-D power Doppler US 1 and 3 months thereafter. RESULTS: 2-D color
      Doppler US detected the absence of blood flow signals in the pedicles of 21
      patients with complete adnexal torsion. Presence of the arterial blood flow
      signals within the pedicle alone was detected in three patients and was
      predictive of a non-viable ovary. The ovarian artery and vein were demonstrated
      in 10 patients with partial torsion. Venous signals alone were isolated in two
      patients with partial adnexal torsion. 3-D power Doppler indices of partially
      twisted adnexa following detorsion have improved significantly 1 (P < 0.05) and 3
      months (P < 0.05), respectively, reaching normal intra-ovarian perfusion values.
      CONCLUSIONS: 2-D color Doppler and 3-D power Doppler US are useful in early
      diagnosis of complete adnexal torsion and follow-up of the ovarian reperfusion
      after detorsion of the partially twisted adnexa.

PMID- 19760451
TI  - Histopathological and electrophysiological study of CO(2), Er:YAG, and CO (2) +
      Er:YAG laser effect on peripheral nerve.
AB  - BACKGROUND: The purpose of this study was to investigate the morphological,
      histopathological, and electrophysiological changes of peripheral nerve after
      CO(2) (carbon dioxide), Er:YAG (erbium:yttrium aluminum garnet), and CO(2) +
      Er:YAG laser irradiation. There have been no comparative reports on CO(2),
      Er:YAG, and CO(2) + Er:YAG laser effects on peripheral nerve. METHODS: Thirty
      Wistar albino rats were randomly assigned to three groups. Group I received
      CO(2), group II Er:YAG, and group III CO(2) + Er:YAG laser irradiation.
      Contralateral untreated sciatic nerves from the same animals were used as
      controls. The effect of laser on the peripheral nerve was assessed
      morphologically, histopathologically, and electrophysiologically after 6 weeks of
      laser irradiation. RESULTS: No significant difference was observed between the
      treated and the untreated nerves. CONCLUSION: The overall findings indicated that
      CO(2), Er:YAG, and CO(2) + Er:YAG lasers may be used safely in nerve tissue
      surgery.

PMID- 19760452
TI  - Review of 1,447 breast augmentation patients using PERTHESE silicone implants.
AB  - INTRODUCTION: A survey of surgeons in Brazil on their experience with PERTHESE
      silicone breast implants was performed. MATERIALS AND METHODS: Surgeons that used
      PERTHESE implants between 2002 and 2008 were surveyed on the shape and volume of
      the implants used, surgical incision site, surgical plane of insertion, key
      postoperative complications, and surgeon and patient satisfaction. RESULTS: The
      survey had a response rate of 20%, with ten surgeons reporting data on 1447
      patients. The majority of the implants used were 200-300 cc, round, and high
      profile. Preference for the traditional inframammary incision site (47% of
      patients) was favored over transaxillary (33%) and periareolar (19%), and both
      subglandular (55%) and submuscular (44%) planes of insertion were used. Over 97%
      of surgeons and patients were satisfied with the results and surgeons indicated
      that the implants were easy to use. CONCLUSIONS: This review demonstrates that
      these implants are safe, maybe easier to introduce than other implants, and
      result in a high level of surgeon and patient satisfaction.

PMID- 19760453
TI  - Intradermal double-layer closure with suture knot contained within incision:
      easy, fast, and safe.

PMID- 19760454
TI  - Integrating landscape analysis and planning: a multi-scale approach for oriented
      management of tourist recreation.
AB  - Tourism and landscape are interdependent concepts. Nature- and culture-based
      tourism are now quite well developed activities and can constitute an excellent
      way of exploiting the natural resources of certain areas, and should therefore be
      considered as key objectives in landscape planning and management in a growing
      number of countries. All of this calls for careful evaluation of the effects of
      tourism on the territory. This article focuses on an integrated spatial method
      for landscape analysis aimed at quantifying the relationship between preferences
      of visitors and landscape features. The spatial expression of the model relating
      types of leisure and recreational preferences to the potential capacity of the
      landscape to meet them involves a set of maps showing degrees of potential
      visitor satisfaction. The method constitutes a useful tool for the design of
      tourism planning and management strategies, with landscape conservation as a
      reference.

PMID- 19760456
TI  - Laryngeal mass with multiple cranial neuropathies as a presenting sign for
      varicella zoster infection.
AB  - The most common presentation of varicella zoster virus (VZV) infection is
      unilateral distribution of herpetic eruptions and neuralgia. Laryngeal
      involvement is considered very rare.

PMID- 19760457
TI  - Age-related differences in laterality of cortical activations in swallowing.
AB  - The present study examined age differences in neural lateralization patterns
      during swallowing and three related tasks, using functional magnetic resonance
      imaging (fMRI). Ten healthy right-handed young adults (mean age = 21.7 years, SD
      = 2.1 years) and nine healthy elders (mean age = 70.2 years, SD = 3.9 years) were
      scanned in a 3-T MRI head scanner. Participants were visually cued to "prepare to
      swallow," "swallow," "tap your tongue," and "clear your throat" in randomized
      order. Laterality preference for each task was examined within and between groups
      using region-of-interest (ROI) analyses in seven areas of the left and right
      primary sensorimotor and premotor cortices. Results of the within-group
      comparisons verified a more active role of the left premotor cortex in motor
      cognitive planning of deglutition in both young and older adults and a more
      active role of selected areas of the right hemisphere during swallowing in young
      adults. Greater variability was seen during tongue tapping and throat clearing in
      both groups. Finally, as people age the cortical hemispheric control of
      swallowing seems to start becoming more symmetrical/bilateral, which may indicate
      neural compensatory mechanisms of the aging brain commonly seen for other motor
      and cognitive functions.

PMID- 19760458
TI  - Effects of therapy in oropharyngeal dysphagia by speech and language therapists:
      a systematic review.
AB  - Medical and paramedical treatments should be evaluated according to current
      standards of evidence-based medicine. Evaluation of therapy in oropharyngeal
      dysphagia fits into this growing interest. A systematic review is given of the
      literature on the effects of therapy in oropharyngeal dysphagia carried out by
      speech therapists. Thus, the review excludes reports of surgical or
      pharmacological treatments. The literature search was performed using the
      electronic databases PubMed and Embase. All available inclusion dates up to
      November 2008 were used. The search was limited to English, German, French,
      Spanish, and Dutch publications. MESH terms were supplemented by using free-text
      words (for the period after January 2005). Fifty-nine studies were included. In
      general, statistically significant positive therapy effects were found. However,
      the number of papers was rather small. Moreover, diverse methodological problems
      were found in many of these studies. For most studies, the conclusions could not
      be generalized; comparison was hindered by the range of diagnoses, types of
      therapies, and evaluation techniques. Many questions remain about the effects of
      therapy in oropharyngeal dysphagia as performed by speech and language
      therapists. Although some positive significant outcome studies have been
      published, further research based on randomized controlled trials is needed.

PMID- 19760459
TI  - Initiation and duration of laryngeal closure during the pharyngeal swallow in
      post-stroke patients.
AB  - As a bolus enters the pharynx during the swallow, the airway is protected by
      laryngeal closure, a process characterized by approximation of the vocal folds
      plus approximation of the arytenoid cartilages to the base of the epiglottis. The
      purpose of this study was to measure initiation of laryngeal closure (ILC) and
      laryngeal closure duration (LCD) in three groups of subjects: (1) ten stroke
      patients who aspirated before and during the swallow (aspirators), (2) ten stroke
      patients who did not aspirate (nonaspirators), and (3) ten normal control
      subjects. Means and standard deviations of ILC and LCD were analyzed for both 5
      ml and 10-ml thin-liquid boluses using a 100-ms timer during subsequent analysis
      of videofluoroscopic swallowing examinations. There were significant differences
      between aspirators and control subjects for both ILC and LCD, and significant
      differences between aspirators and nonaspirators for ILC. There were no
      significant differences between aspirators and nonaspirators for LCD. Both
      delayed ILC and reduced LCD were associated with post-stroke aspiration. Delayed
      ILC is a significant indicator of overall risk of aspiration. Clinical
      implications for these findings are discussed.

PMID- 19760460
TI  - Long-term results of external upper esophageal sphincter myotomy for
      oropharyngeal Dysphagia.
AB  - The aim of this work was to assess the efficacy of external myotomy of the upper
      esophageal sphincter (UES) for oropharyngeal dysphagia. In the period 1991-2006,
      28 patients with longstanding dysphagia and/or aspiration problems of different
      etiologies underwent UES myotomy as a single surgical treatment. The main
      symptoms were difficulties in swallowing of a solid-food bolus, aspiration, and
      recurrent incidents of solid-food blockages. Pre- and postoperative manometry and
      videofluoroscopy were used to assess deglutition and aspiration. Outcome was
      defined as success in the case of complete relief or marked improvement of
      dysphagia and aspiration and as failure in the case of partial improvement or no
      improvement. Initial results showed success in 21 and failure in 7 patients. The
      best outcomes were observed in patients with dysphagia of unknown origin,
      noncancer-related iatrogenic etiology, and neuromuscular disease. No correlation
      was found between preoperative constrictor pharyngeal muscle activity and success
      rate. After follow-up of more than 1 year, 20 patients were marked as success and
      3 as failure. All successful patients had full oral intake with a normal bolus
      consistency without clinically significant aspiration. We conclude that in select
      cases of oropharyngeal dysphagia success may be achieved by UES myotomy with
      restoration of oral intake of normal bolus consistency.

PMID- 19760461
TI  - Interaural correlation fails to account for detection in a classic binaural task:
      dynamic ITDs dominate N0Spi detection.
AB  - Binaural signal detection in an NoSpi task relies on interaural disparities
      introduced by adding an antiphasic signal to diotic noise. What metric of
      interaural disparity best predicts performance? Some models use interaural
      correlation; others differentiate between dynamic interaural time differences
      (ITDs) and interaural level differences (ILDs) of the effective stimulus. To
      examine the relative contributions of ITDs and ILDs in binaural detection, we
      developed a novel signal processing technique that selectively degrades different
      aspects (potential cues) of binaural stimuli (e.g., only ITDs are scrambled).
      Degrading a particular cue will affect performance only if that cue is relevant
      to the binaural processing underlying detection. This selective scrambling
      technique was applied to the stimuli of a classic N0Spi task in which the
      listener had to detect an antiphasic 500-Hz signal in the presence of a diotic
      wideband noise masker. Data obtained from five listeners showed that (1)
      selective scrambling of ILDs had little effect on binaural detection, (2)
      selective scrambling of ITDs significantly degraded detection, and (3) combined
      scrambling of ILDs and ITDs had the same effect as exclusive scrambling of ITDs.
      Regarding the question which stimulus properties determine detection, we conclude
      that for this binaural task (1) dynamic ITDs dominate detection performance, (2)
      ILDs are largely irrelevant, and (3) interaural correlation of the stimulus is a
      poor predictor of detection. Two simple stimulus-based models that each reproduce
      all binaural aspects of the data quite well are described: (1) a single-parameter
      detection model using ITD variance as detection criterion and (2) a compressive
      transformation followed by a crosscorrelation analysis. The success of both of
      these contrasting models shows that our data alone cannot reveal the mechanisms
      underlying the dominance of ITD cues. The physiological implications of our
      findings are discussed.

PMID- 19760462
TI  - Creation of a novel recuperative pain medicine service to optimize postoperative
      analgesia and enhance patient satisfaction.
AB  - Many patients have difficulty with pain control after transition from patient
      controlled analgesia modalities to oral analgesics. The creation of a
      Recuperative Pain Medicine (RPM) service was intended to bridge this gap in pain
      management at the Hospital for Special Surgery. Specific goals were to improve
      patient and staff satisfaction with management of postoperative oral analgesics
      by improving clinical care, administrative policies, and patient and staff
      education. Primary outcome measures for improved satisfaction were Press Ganey
      surveys and staff surveys. From inception in Aug 2007 to Dec 2008, RPM has seen
      6,305 patients for discharge planning and education and 997 patients for pain
      management consultation. Administrative and educational accomplishments have
      included creation of a patient "Helpline" for emergent phone questions regarding
      postdischarge home pain medications, a policy for prescribing pain medications
      for home discharge, patient education booklets, a pain management webpage on the
      Hospital for Special Surgery website, and direct education of staff. Press Ganey
      measurements of patient satisfaction increased from 87th percentile up to the
      99th percentile among peer institutions since the implementation of RPM. Staff
      satisfaction was 92% positive regarding the RPM service's function and patient
      management. An RPM appears to be an effective means to optimize postoperative
      pain management after transition off patient-controlled analgesia devices.
      Further research is needed to ascertain the exact cost-benefit and potential
      impact on postoperative quality-of-life measurements.

PMID- 19760463
TI  - Extinction and chaotic patterns in map lattices under hostile conditions.
AB  - Population dynamics in spatially extended systems can be modeled by Coupled Map
      Lattices (CML). We employ such equations to study the behavior of populations
      confined to a finite patch surrounded by a completely hostile environment. By
      means of the Galerkin projection and the normal solution ansatz, we are able to
      find analytical expressions for the critical patch size and show the existence of
      chaotic patterns. The analytical solutions provided are shown to fit, under the
      appropriate approximations, the dynamics of a logistic map. This interesting
      result, together with our discussion, suggests the existence of a universal class
      of spatially extended systems directly linked to the well-known characteristics
      of the logistic map.

PMID- 19760464
TI  - Morphological analysis of the carpal tunnel.
AB  - Although carpal tunnel release is one of the most commonly performed procedures
      in the USA, the morphology of the carpal tunnel as determined previously in the
      literature has been questioned. Previous methodology has been questioned for
      accuracy by recent studies. The purpose of this study was to perform a
      morphological analysis of the carpal tunnel and correlate carpal tunnel and hand
      dimensions. The carpal tunnels of ten cadaveric specimens were emptied of their
      contents and a silicone cast of the carpal tunnel was then created. This cast was
      then digitized, and the dimensions of the carpal tunnel were calculated. These
      dimensions were compared with the measured hand dimensions of the specimens. The
      width, depth, tilt angle, length, cross-sectional area, and volume of the carpal
      tunnel were 19.2 +/- 1.7 mm, 8.3 +/- 0.9 mm, 14.8 +/- 7.8 degrees , 12.7 +/- 2.5
      mm, 134.9 +/- 23.6 mm(2), and 1,737 +/- 542 mm(3), respectively. Width, depth,
      and cross-sectional area did not change significantly along the length of the
      carpal tunnel, but tilt angle did. The width of the palm strongly correlates with
      the width of the carpal tunnel. Other dimensional correlations did not reach
      statistical significance. The carpal tunnel is of uniform dimension along its
      length. The long axis of the carpal tunnel in cross-section rotates volarly from
      the radial side of the hand increasingly with distal progression along the carpal
      tunnel. Based on our analysis of ten cadaveric specimens, the width of the carpal
      tunnel may be estimated by the width of the palm using the equation: [Formula:
      see text].

PMID- 19760465
TI  - Matrix metalloproteinase 2 activity decreases in human periodontal ligament
      fibroblast cultures submitted to simulated orthodontic force.
AB  - Orthodontic force compresses the periodontal ligament promoting the expression of
      pro-inflammatory mediators and matrix metalloproteinases responsible for tooth
      movement. The extent in time while periodontal cells are being treated and the
      increment in the amount of mechanical stress caused by the orthodontic force is
      thought to regulate the levels of metalloproteinases in the periodontal tissue.
      To study the possible regulation in the activity of metalloproteinases 2, 3, 7,
      9, and 10 by simulated orthodontic force, human periodontal ligament fibroblast
      cultures were centrifuged (141 * g) for 30, 60, 90, and 120 min, simulating the
      orthodontic force. Cell viability, protein quantification, and activity of
      metalloproteinases by zymography were evaluated at 24, 48, and 72 h after
      centrifugation in both cell lysates and growth medium. The activity of the 72-kDa
      matrix metalloproteinase 2 was decreased at 24 h regardless of the duration of
      centrifugation and at 48 h in cells centrifuged for 30 min only. Decrease in the
      amount of total protein in lysates was seen at 48 and 72 h with no change in cell
      viability. The data seem to indicate that the amount of mechanical stress
      regulates the levels of secreted matrix metalloproteinase 2. In addition, the
      centrifugation as a model for simulated orthodontic force may be used as a simple
      and reliable method to study the role played by matrix metalloproteinases in
      periodontal ligament when submitted to mechanical force as occurring during tooth
      movement.

PMID- 19760466
TI  - Confirmatory factor analysis of the Beck Depression Inventory in obese
      individuals seeking surgery.
AB  - BACKGROUND: The Beck Depression Inventory (BDI) is frequently employed as measure
      of depression in studies of obesity. The aim of the study was to assess the
      factorial structure of the BDI in obese patients prior to bariatric surgery.
      METHODS: Confirmatory factor analysis was conducted on the current published
      factor analyses of the BDI. Three published models were initially analysed with
      two additional modified models subsequently included. A sample of 285 patients
      presenting for Lap-Band surgery was used. RESULTS: The published bariatric model
      by Munoz et al. was not an adequate fit to the data. The general model by Shafer
      et al. was a good fit to the data but had substantial limitations. The weight
      loss item did not significantly load on any factor in either model. A modified
      Shafer model and a proposed model were tested, and both were found to be a good
      fit to the data with minimal differences between the two. A proposed model, in
      which two items, weight loss and appetite, were omitted, was suggested to be the
      better model with good reliability. CONCLUSIONS: The previously published factor
      analysis in bariatric candidates by Munoz et al. was a poor fit to the data, and
      use of this factor structure should be seriously reconsidered within the obese
      population. The hypothesised model was the best fit to the data. The findings of
      the study suggest that the existing published models are not adequate for
      investigating depression in obese patients seeking surgery.

PMID- 19760467
TI  - Case report: Cementless stem stabilization after intraoperative fracture: a
      radiostereometric analysis.
AB  - We present the case of a patient with intraoperative femoral fracture during THA,
      which was repaired using cerclage fixation and insertion of an hydroxyapatite
      coated cementless stem. The patient was evaluated postoperatively using
      radiostereometry during a 2-year course, and despite a large amount of subsidence
      and rotation, stabilization occurred and was maintained by 6 months. By
      evaluating the pattern of stem migration after intraoperative fracture, this case
      shows, even in the presence of instability, a successful clinical outcome can be
      achieved using an hydroxyapatite-coated cementless stem.

PMID- 19760468
TI  - In vivo kinematics after a cruciate-substituting TKA.
AB  - Patterns of motion in the native knee show substantial variability. Guided motion
      prosthetic designs offer stability but may limit natural variability. To assess
      these limits, we therefore determined the in vivo kinematic patterns for patients
      having a cruciate-substituting TKA of one design and determined the intersurgeon
      variability associated with a guided-motion prosthetic design. Three-dimensional
      femorotibial contact positions were evaluated for 86 TKAs in 80 subjects from
      three different surgeons using fluoroscopy during a weightbearing deep knee bend.
      The average posterior femoral rollback of the medial and lateral condyles for all
      TKAs from full extension to maximum flexion was -14.0 mm and -23.0 mm,
      respectively. The average axial tibiofemoral rotation from full extension to
      maximum flexion for all TKAs was 10.8 degrees. The average weightbearing range of
      motion (ROM) was 109 degrees (range, 60 degrees-150 degrees; standard deviation,
      18.7 degrees). Overall, the TKA showed axial rotation patterns similar to those
      of the normal knee, although less in magnitude. Surgeon-to-surgeon comparison
      revealed dissimilarities, showing the surgical technique and soft tissue handling
      influence kinematics in a guided-motion prosthetic design. LEVEL OF EVIDENCE:
      Level III, therapeutic study. See Guidelines for Authors for a complete
      description of levels of evidence.

PMID- 19760469
TI  - Are endogenous BMPs necessary for bone healing during distraction osteogenesis?
AB  - Previous reports suggest the application of exogenous BMPs can accelerate bone
      formation during distraction osteogenesis (DO). However, there are drawbacks
      associated with the use of exogenous BMPs. A possible alternative to the use of
      exogenous BMPs is to upregulate the expression of endogenous BMPs. Since DO
      results in spontaneously generated de novo bone formation in a uniform
      radiographic, histological, and biomechanical temporal sequence, a genetically
      engineered model lacking endogenous BMP2 should have measurable deficits in bone
      formation at different time points. We performed DO on BMP2(fl/+) and BMP2(fl/+
      cre) mice using a miniature Ilizarov fixator. Distracted samples were collected
      at various time points and analyzed using real time-quantitative PCR, lCT,
      radiology, immunohistochemistry, histology, and biomechanical testing.
      Immunohistochemical studies of 34-day heterozygous samples showed reduced
      expression of BMP2, BMP7, BMPR1a, ACTR1, and ACTR2b. lCT analysis of 51-day
      heterozygous samples revealed a decrease in trabecular number and increase in
      trabecular separation. Biomechanical testing of 51-day heterozygous samples
      revealed decreased stiffness and increased ultimate displacement. Radiological
      analysis showed the heterozygotes contained a decreased bone fill score at 17,
      34, and 51 days. These data suggest endogenous BMPs are important for bone
      healing and manipulating endogenous BMPs may help accelerate bone consolidation
      during DO.

PMID- 19760470
TI  - Anatomic study of the abductor pollicis longus: a source for grafting material of
      the hand.
AB  - Interposition grafting material is used frequently to treat osteoarthritis of the
      base of the thumb or tendinous and ligamentous injuries of the hand. The
      observation of duplicated tendons in the first dorsal compartment of the hand
      prompted us to explore the possibility of using the accessory abductor pollicis
      longus (AAPL) tendon as grafting material. Based on dissections of 78 cadaveric
      upper limbs, we describe the number of tendons in the first dorsal compartment of
      the hand, the number of muscle bellies, their innervation, their insertion site,
      and the tendon dimensions to determine whether the AAPL can be considered a true
      tendon. The AAPL was present in 85% of the hands. Average length, width, and
      thickness (in millimeters) of the APL were of 69.3, 5.2, and 2.1, respectively.
      Average length, width, and thickness (in millimeters) of the AAPL were of 69.2,
      3.3, and 1.6, respectively. No differences in dimension of the tendons were found
      between the APL and the AAPL. The dimensions of the tendinous portion of the AAPL
      are similar to those of the APL and can be considered a true tendon. When
      present, the AAPL is a suitable source of local grafting material.

PMID- 19760471
TI  - Classification and clinical significance of acromial spur in rotator cuff tear:
      heel-type spur and rotator cuff tear.
AB  - Acromial spurs reportedly relate to the impingement syndrome and rotator cuff
      tears. We classified the morphologic characteristics of the acromion (shape and
      thickness) and acromial spurs and determined whether they correlated with rotator
      cuff tears. We measured acromial shape and thickness using simple radiography and
      MR arthrography or CT arthrography in 106 patients with full-thickness rotator
      cuff tears and in 102 patients without tears. Acromial spurs could be classified
      morphologically into six types: heel, lateral/anterior traction, lateral/anterior
      bird beak, and medial. We found acromial spurs in 142 of the 208 patients (68%),
      and their incidence increased with age. The acromial spur was more common in the
      cuff tear group. The heel type was most common and detected in 59 patients (56%)
      in the cuff tear group and in 36 patients (35%) in the control group. The flat
      acromion was more common (60%) than curved and hooked acromion; however, there
      was no major difference between acromial shape and cuff tear. The mean acromial
      thickness was 8.0 mm, and the cuff tear group had thicker acromion. These data
      suggest acromial spurs can be classified according to the distinct morphology,
      and the most common heel-type spur might be a risk factor for full-thickness
      rotator cuff tears. LEVEL OF EVIDENCE: Level IV, diagnostic study. See Guidelines
      for Authors for a complete description of levels of evidence.

PMID- 19760472
TI  - Comparing patient outcomes after THA and TKA: is there a difference?
AB  - Both primary total hip (THA) and knee (TKA) arthroplasty relieve pain, restore
      function, and increase mobility. Despite these successes, there is controversy as
      to whether THA or TKA provides greater or similar improvement. We therefore
      compared primary THA and TKA patient results in terms of (1) willingness to have
      surgery again; (2) WOMAC change score; (3) whether expectations were met; and (4)
      satisfaction. Patients undergoing primary THA were more willing to undergo their
      surgery again (THA 96%, TKA 89%), demonstrated greater WOMAC change scores, more
      frequently reported their expectations were met (THA 78%, TKA 70%), and expressed
      greater overall satisfaction (THA 89%, TKA 81%). In addition, patients undergoing
      THA expressed higher satisfaction with pain reduction while performing activities
      (ie, walking, stairs, and sitting/lying) and their ability to perform daily
      activities (ie, stairs, transportation, getting up, lying in bed, and light
      domestic duties) when compared with patients undergoing TKA. Our data suggest
      primary THA offers superior short-term outcomes when compared with primary TKA.
      LEVEL OF EVIDENCE: Level II, prognostic study. See Guidelines for Authors for a
      complete description of levels of evidence.

PMID- 19760473
TI  - Obesity: can behavioral economics help?
AB  - BACKGROUND: Consumers regularly and predictably behave in ways that contradict
      standard assumptions of economic analysis such that they make decisions that
      prevent them from reaching rationally intended goals. These contradictions play a
      significant role with respect to consumers' food decisions and the effect these
      decisions have on their health. DISCUSSION: Food decisions that are rationally
      derived include those that trade short-term gains of sensory pleasure (hedonic)
      for longer term gains of health and wellness (utilitarian). However, extra
      rational food decisions are much more common. They can occur because of the
      contexts in which they are made--such as being distracted or pressed for time. In
      these contexts, heuristics (or rules of thumb) are used. Because food decisions
      are made with little cognitive involvement, food policies designed to appeal to
      highly cognitive thought (e.g., fat taxes, detailed information labels) are
      likely to have little impact. Furthermore, food marketing environments influence
      not only what foods consumers buy but also how much. As a general principle, when
      individuals do not behave in their own interest, markets will feed perverse and
      sub-optimal behaviors. CONCLUSION: Given the limited ability of individuals to
      retain and use accurate health information coupled with varying levels of self
      control, profit motivations of marketers can become predatory--though not
      necessarily malicious. Alternative policy options that do not restrict choice are
      outlined, which enable consumers to make better decisions. These options allow
      for profit motivations of marketers to align with the long-term well being of the
      consumer.

PMID- 19760474
TI  - The variable functional effects of the pacing site  in normal and scarred
      ventricles.
AB  - BACKGROUND: The pacing site has been shown to influence functional improvement
      with cardiac resynchronization therapy. We evaluated the effects of the pacing
      site on left ventricular (LV) function in an animal model. METHODS AND RESULTS:
      Equilibrium radionuclide angiography was acquired in sinus rhythm (NSR) and with
      ventricular pacing, from three pacing sites in seven normal and eight infarcted
      dogs. QRS duration, electrical activation pattern, wall motion, LV ejection
      fraction (EF), synchrony of ventricular contraction, and mean arterial pressure
      (MAP), were related to the pacing site and infarct size, during each of 120
      episodes. Little changed during pacing in normals. In infarcted dogs, LV wall
      motion, and synchrony worsened, LVEF and MAP often fell. These changes related to
      altered activation patterns which were influenced by the pacing site but were not
      related to infarct size. CONCLUSIONS: Hemodynamic and functional LV changes after
      infarction were found to vary with the pacing site and associated conduction and
      synchrony.

PMID- 19760475
TI  - Selective vulnerability in striosomes and in the nigrostriatal dopaminergic
      pathway after methamphetamine administration : early loss of TH in striosomes
      after methamphetamine.
AB  - Methamphetamine (METH), a commonly abused psychostimulant, causes dopamine
      neurotoxicity in humans, rodents, and nonhuman primates. This study examined the
      selective neuroanatomical pattern of dopaminergic neurotoxicity induced by METH
      in the mouse striatum. We examined the effect of METH on tyrosine hydroxylase
      (TH) and dopamine transporter (DAT) immunoreactivity in the different
      compartments of the striatum and in the nucleus accumbens. The levels of dopamine
      and its metabolites, 3,4-dihidroxyphenylacetic acid and homovanillic acid, as
      well as serotonin (5-HT) and its metabolite, 5-hydroxyindolacetic acid, were also
      quantified in the striatum. Mice were given three injections of METH (4 mg/kg,
      i.p.) at 3 h intervals and sacrificed 7 days later. This repeated METH injection
      induced a hyperthermic response and a decrease in striatal concentrations of
      dopamine and its metabolites without affecting 5-HT concentrations. In addition,
      the drug caused a reduction in TH- and DAT-immunoreactivity when compared to
      saline-treated animals. Interestingly, there was a significantly greater loss of
      TH- and DAT-immunoreactivity in striosomes than in the matrix. The predominant
      loss of dopaminergic terminals in the striosomes occurred along the rostrocaudal
      axis of the striatum. In contrast, METH did not decrease TH- or DAT
      immunoreactivity in the nucleus accumbens. These results provide the first
      evidence that compartments of the mouse striatum, striosomes and matrix, and
      mesolimbic and nigrostriatal pathways have different vulnerability to METH. This
      pattern is similar to that observed with other neurotoxins such as MPTP, the most
      widely used model of Parkinson's disease, in early Huntington's disease and
      hypoxic/ischemic injury, suggesting that these conditions might share mechanisms
      of neurotoxicity.

PMID- 19760476
TI  - Acute L: -DOPA effect on hydroxyl radical- and DOPAC-levels in striatal
      microdialysates of parkinsonian rats.
AB  - The object of the current study was to determine the effect of L: -3,4
      dihydroxyphenylalanine (L: -DOPA) on the in vivo striatal microdialysate levels
      of the respective dopamine and serotonin metabolites 3,4-dihydroxyphenlalanine
      (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA) and hydroxyl radical level
      (HO(*); 2,3- and 2,5-dihydroxybenzoic acid, 2,3- and 2,5-DHBA) in adult rats made
      parkinsonian by treatment at 3 days after birth with the neurotoxin 6
      hydroxydopamine (6-OHDA; 66.7 microg, base form, on each side; desipramine
      pretreatment, 1 h). Using HPLC/ED we found that in 6-OHDA-lesioned rats the basal
      striatal extraneuronal level of DOPAC was dramatically reduced and constituted
      only approximately 4.5% of referenced value (intact rats). Conversely, the
      striatal microdialysate level of 5-HIAA was elevated 2-fold in 6-OHDA-lesioned
      rats. Acute L: -DOPA (60 mg/kg i.p.; S-carbidopa pretreatment, 12.5 mg/kg i.p.,
      30 min) produced a rapid rise in the extraneuronal DOPAC in both tested groups
      but to a much greater extent in intact rats (P < 0.05). Levels of HO(*) (spin
      trap products of salicylate, 2,3- and 2,5-DHBA) were elevated 2-fold in 6-OHDA
      lesioned rats. However, L: -DOPA did not enhance HO(*) production; acute 6-OHDOPA
      treatment (60 mg/kg i.p.) also did not alter HO(*) production. In summary, L: 
      DOPA, an effective drug in ameliorating PD symptoms, did not acutely pose a risk
      for HO(*) generation in parkinsonian rats. We conclude that L: -DOPA is not
      likely to generate reactive oxygen species in humans nor is L: -DOPA likely to
      accelerate PD in humans.

PMID- 19760478
TI  - Outcome of sliding inguinal hernia repair.
AB  - PURPOSE: Sliding inguinal hernias represent a small proportion of inguinal
      hernias but become more common with advancing age. The most recent review is
      based on a series published over 50 years ago. There are, however, many case
      reports of unusual presentations in girls. METHODS: We performed a review of a
      prospectively kept electronic record of all operations performed at Logan
      Hospital since 2003 in order to document the clinical characteristics of sliding
      inguinal hernias in the twenty-first century. RESULTS: Thirty-one males underwent
      predominantly anterior repair of a sliding hernia after a median of 9 months of
      symptoms (2.9% of all hernia repairs-32/1,092). Approximately two-thirds of
      hernias were left sided. There were five minor and two technical complications.
      Follow-up ranged from 3 weeks to 3 years. Two recurrences have been repaired.
      CONCLUSIONS: Sliding inguinal hernias continue to test the surgeon's
      understanding of the inguinal canal's anatomy and technical expertise with a
      significant rate of technical complications and recurrence.

PMID- 19760480
TI  - L-2-hydroxyglutaric aciduria diagnosed in an adult presenting with acute
      deterioration.

PMID- 19760481
TI  - Primary sclerosing cholangitis with elevated serum IgG4 levels and/or
      infiltration of abundant IgG4-positive plasma cells.
AB  - Immunoglobin G4-related sclerosing cholangitis (IgG4-SC) is recognized as one of
      the systemic sclerosing diseases characterized by abundant IgG4-positive plasma
      cells with effective steroid therapy. On the other hand, primary sclerosing
      cholangitis (PSC), recognized as a sclerosing cholangitis of unknown origin
      without steroid efficacy, has been often clinically confused with IgG4-SC. To
      date, the prognosis of IgG4-SC is unclear, while the prognosis of PSC is well
      known to be poor. Therefore, it is clinically very important to be able to
      distinguish IgG4-SC from PSC. However, at the present time it still remains
      unclear whether PSC may sometimes be misdiagnosed as IgG4-SC or not. Herein, we
      report three rare cases of PSC with elevated serum IgG4 levels and/or an
      infiltration of abundant IgG4-positive plasma cells in the liver: a young male
      with ulcerative colitis (UC), and elderly female and a young female, each with
      elevated serum IgG4 levels. The first two patients showed infiltration of
      abundant IgG4-positive plasma cells in the portal area of the liver without
      response to steroid therapy. From our experiences, we emphasize that some
      patients with PSC, who do not respond to steroid therapy, show elevated serum
      IgG4 levels and/or infiltration of abundant IgG4-positive plasma cells, although
      the mechanism still remains unclear.

PMID- 19760482
TI  - Immunosuppressive treatment in patient with pure red cell aplasia associated with
      chronic myelomonocytic leukemia: harm or benefit?
AB  - Acquired pure red cell aplasia (PRCA) can be primary or secondary to other
      diseases. PRCA association with chronic myelomonocytic leukemia (CMML) is very
      rarely reported. Although treatment is directed to underlying cause in secondary
      PRCA treatment, optimal treatment in patients with CMML and PRCA is unknown,
      because only four case reports are available. In addition, the effect of
      hypomethylating agents can be detrimental due to myelosuppression, at least in
      the early phase of treatment. Bone marrow examination of a 66-year-old woman with
      severe anemia revealed PRCA and was suspicious for CMML. There was no HLA-matched
      sibling for bone marrow transplantation. The patient received immunosuppressive
      therapy with steroids and cyclosporine with temporary response in anemia;
      however, progressed to acute leukemia over 8 months and died. Immunosuppressive
      therapy in patients with CMML and PRCA should be cautiously used because it may
      accelerate acute leukemia transformation.

PMID- 19760483
TI  - National questionnaire survey of TMA.
AB  - A questionnaire survey of Japanese patients with thrombotic microangiopathy (TMA)
      was carried out to investigate the frequency, laboratory abnormalities, and
      outcome in 2004. Out of 185 patients, there were 13 with familial TMA and 172
      with acquired TMA. In acquired TMA, there were 66 with Escherichia coli O-157
      infection (O-157)-related TMA, 35 with ADAMTS13-related TMA, and 22 with other
      types of TMA. The frequency of TMA in O-157-related TMA was high in patients from
      0- to 15-year-old, and acquired TMA without O-157 was frequently observed in
      patients ranging from 31 to 65 years of age. In the treatment of acquired TMA,
      including plasma exchange (PE), steroid, antiplatelet agent, and anticoagulant,
      PE was carried out in 94.3% of ADAMTS13-related TMA, 77.3% of other TMA, and 7.6%
      of O-157-related TMA. The efficacy of PE and steroid therapy tended to be higher
      in ADAMTS13 TMA than in other types of TMA. The complete remission rate is the
      highest in O-157 TMA. The mortality rate was the lowest for O-157 TMA, and this
      rate also tended to be lower in ADAMTS13-related TMA than in other types of TMA.
      However, the determination of ADAMTS13 was not universal in Japan at the time of
      this questionnaire.

PMID- 19760484
TI  - Centrally administered ghrelin potently inhibits water intake induced by
      angiotensin II and hypovolemia in rats.
AB  - Ghrelin is a potent, centrally acting orexigenic hormone. Recently, we showed
      that centrally administered ghrelin is a potent antidipsogenic hormone in 24-h
      water deprived rats. In this study, we examined the effect of
      intracerebroventricular (icv) injection of ghrelin on angiotensin II (AII)
      induced water intake in rats. We also examined the effects of icv injection of
      ghrelin on drinking induced by intraperitoneal injection of an isotonic
      polyethylene glycol (PEG) solution that causes isotonic hypovolemia. Water intake
      induced by the icv injection of AII or ip injection of PEG was significantly
      reduced after icv injection of ghrelin, although food intake was stimulated by
      the hormone. The drinking induced by AII was also inhibited by the icv
      administration of 4alpha-phorbol 12, 13-didecanoate, an agonist of the
      osmosensitive TRPV4 channel. This study showed that ghrelin is a potent
      antidipsogenic peptide by antagonizing general dipsogenic mechanisms including
      those activated by AII and hypovolemia in rats.

PMID- 19760485
TI  - The effect of electroaucpuncture for 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      induced proteomic changes in the mouse striatum.
AB  - Using a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) Parkinson's disease
      mouse model, we investigated protein expression changes associated with the
      action of electroacupuncture (EA) in the mouse striatum. Twelve-week-old male
      C57BL/6 mice were injected intraperitoneally with 30 mg/kg of MPTP at 24-h
      intervals for 5 days, and the 100-Hz EA stimulation was performed at GB34 and
      GB39 once a day for 12 days consecutively from the first injection. With the EA,
      the MPTP-induced dopaminergic neuronal destruction was reduced. Of the 13
      proteins that were differentially expressed between control and MPTP treated
      mice, cytosolic malate dehydrogenase, munc18-1, and hydroxyacylglutathione
      hydrolase, which were increased by MPTP, and cytochrome c oxidase subunit Vb,
      which was decreased by MPTP, were restored to the level of the saline group after
      EA treatment. These proteins are likely related to cellular metabolism.
      Altogether, we propose that the EA may exert neuroprotective effects in mice
      striatum through reducing MPTP-induced toxicity such as oxidative stress.

PMID- 19760487
TI  - Regulated expression of pancreatic triglyceride lipase after rat traumatic brain
      injury.
AB  - Pancreatic triglyceride lipase (PTL), an enzyme of digestive system, plays very
      important roles in the digestion and absorption of lipids. However, its
      distribution and function in the central nervous system (CNS) remains unclear. In
      the present study, we mainly investigated the expression and cellular
      localization of PTL during traumatic brain injury (TBI). Western blot and RT-PCR
      analysis revealed that PTL was present in normal rat brain cortex. It gradually
      increased, reached a peak at the 3rd day after TBI, and then decreased. Double
      immunofluorescence staining showed that PTL was co-expressed with neuron, but had
      a few colocalizations in astrocytes. When TBI occurred in the rat cortex, the
      expression of PTL gradually increased, reached the peak at the 3rd day after TBI,
      and then decreased. Importantly, more PTL was colocalized with astrocytes, which
      is positive for proliferating cell nuclear antigen (PCNA). In addition, Western
      blot detection showed that the 3rd day post injury was not only the proliferation
      peak indicated by the elevated expression of PCNA, glial fibrillary acidic
      protein (GFAP) and cyclin D1, but also the apoptotic peak implied by the
      alteration of caspase-3 and bcl-2. These data suggested that PTL may be involved
      in the pathophysiology of TBI and PTL may be complicated after injury, more PTL
      was colocalized with astrocytes. Importantly, injury-induced expression of PTL
      was colabelled by proliferating cell nuclear antigen (proliferating cells
      marker), and the western blot for GFAP, PCNA and cyclin D1, showed that 3 days
      post injury was the proliferation peak, in coincidence to it, the protein level
      change of caspase-3 and bcl-2 revealed that the stage was peak of apoptotic too.
      These data suggested that PTL may be involved in the pathophysiology of TBI and
      that PTL may be implicated in the proliferation of astrocytes and the recovery of
      neurological outcomes. But the inherent mechanisms remained unknown. Further
      studies are needed to confirm the exact role of PTL after brain injury.

PMID- 19760488
TI  - Can cross country differences in return-to-work after chronic occupational back
      pain be explained? An exploratory analysis on disability policies in a six
      country cohort study.
AB  - INTRODUCTION: There are substantial differences in the number of disability
      benefits for occupational low back pain (LBP) among countries. There are also
      large cross country differences in disability policies. According to the
      Organization for Economic Cooperation and Development (OECD) there are two
      principal policy approaches: countries which have an emphasis on a compensation
      policy approach or countries with an emphasis on an reintegration policy
      approach. The International Social Security Association initiated this study to
      explain differences in return-to-work (RTW) among claimants with long term sick
      leave due to LBP between countries with a special focus on the effect of
      different disability policies. METHODS: A multinational cohort of 2,825
      compensation claimants off work for 3-4 months due to LBP was recruited in
      Denmark, Germany, Israel, the Netherlands, Sweden, and the United States.
      Relevant predictors and interventions were measured at 3 months, one and 2 years
      after the start of sick leave. The main outcome measure was duration until
      sustainable RTW (i.e. working after 2 years). Multivariate analyses were
      conducted to explain differences in sustainable RTW between countries and to
      explore the effect of different disability policies. RESULTS: Medical and work
      interventions varied considerably between countries. Sustainable RTW ranged from
      22% in the German cohort up to 62% in the Dutch cohort after 2 years of follow
      up. Work interventions and job characteristics contributed most to these
      differences. Patient health, medical interventions and patient characteristics
      were less important. In addition, cross-country differences in eligibility
      criteria for entitlement to long-term and/or partial disability benefits
      contributed to the observed differences in sustainable RTW rates: less strict
      criteria are more effective. The model including various compensation policy
      variables explained 48% of the variance. CONCLUSIONS: Large cross-country
      differences in sustainable RTW after chronic LBP are mainly explained by cross
      country differences in applied work interventions. Differences in eligibility
      criteria for long term disability benefits contributed also to the differences in
      RTW. This study supports OECD policy recommendations: Individual packages of work
      interventions and flexible (partial) disability benefits adapted to the
      individual needs and capacities are important for preventing work disability due
      to LBP.

PMID- 19760489
TI  - Predicting return to work in employees sick-listed due to minor mental disorders.
AB  - OBJECTIVE: To investigate which factors predict return to work (RTW) after 3 and
      6 months in employees sick-listed due to minor mental disorders. METHODS: Seventy
      GPs recruited 194 subjects at the start of sick leave due to minor mental
      disorders. At baseline (T0), 3 and 6 months later (T1 and T2, respectively),
      subjects received a questionnaire and were interviewed by telephone. Using
      multivariate logistic regression analyses, we developed three prediction models
      to predict RTW at T1 and T2. RESULTS: The RTW rates were 38% after 3 months (T1)
      and 61% after 6 months (T2). The main negative predictors of RTW at T1 were: (a)
      a duration of the problems of more than 3 months before sick leave; and (b)
      somatisation. The main negative predictors of RTW at T2 were: (a) a duration of
      the problems of more than 3 months before sick leave; (b) more than 3 weeks of
      sick leave before inclusion in the study; and (c) anxiety. The main negative
      predictors of RTW at T2 for those who had not resumed work at T1 were: (a) more
      than 3 weeks of sick leave before inclusion in the study; and (b) depression at
      T1. The predictive power of the models was moderate with AUC-values between 0.695
      and 0.763. CONCLUSIONS: The main predictors of RTW were associated with the
      severity of the problems. A long duration of the problems before the occurrence
      of sick leave and a long duration of sick leave before seeking help predict a
      relatively small probability to RTW within 3-6 months. High baseline somatisation
      and anxiety, and high depression after 3 months make the prospect even worse.
      Since these predictors are readily assessable with just a few questions and a
      symptom questionnaire, this opens the opportunity to select high-risk employees
      for a

PMID- 19760491
TI  - "The third category of mental disorders" by Xu Youxin.

PMID- 19760492
TI  - Assessing diabetes practices in clinical settings: precursor to building
      community partnerships around disease management.
AB  - Many recommended best practices exist for clinical and community diabetes
      management and prevention. However, in many cases, these recommendations are not
      being fully utilized. It is useful to gain a sense of currently utilized and
      needed practices when beginning a partnership building effort to ameliorate such
      practice problems. The purpose of this study was to assess current practices in
      clinical settings within the Brazos Valley in preparation for beginning a
      community-based participatory research project on improving diabetes prevention
      and management in this region. Fifty-seven physicians with admission privileges
      to a regional health system were faxed a survey related to current diabetes
      patient loads, knowledge and implementation of diabetes-related best practices,
      and related topics. Both qualitative and quantitative examination of the data was
      conducted. Fifteen percent of responding providers indicated they implemented
      diabetes prevention best practices, with significant differences between primary
      care physicians and specialists. Respondents indicated a need for educational and
      counseling resources, as well as an increased health-care workforce in the
      region. The utilization of a faxed-based survey proved an effective means for
      assessing baseline data as well as serving as a catalyst for further discussion
      around coalition development. Results indicated a strong need for both clinical
      and community-based services regarding diabetes prevention and management, and
      provided information and insight to begin focused community dialogue around
      diabetes prevention and management needs across the region. Other sites seeking
      to begin similar projects may benefit from a similar process.

PMID- 19760493
TI  - A classification and meta-analysis of community-based directly observed therapy
      programs for tuberculosis treatment in developing countries.
AB  - In many developing countries, Directly Observed Therapy (DOT) for tuberculosis
      has been undertaken mainly in the clinic setting. However, clinic-based DOT may
      create a high patient load in already overburdened health facilities and increase
      barriers to care by requiring patients to travel to clinic frequently for
      therapy. Community-based DOT (CBDOT) may overcome some of these problems. This
      aims of this review are (a) to describe the main features of CBDOT programs, and
      (b) to compare features and outcomes of CBDOT programs that do and do not offer
      financial reward for CBDOT providers. Ten major features define CBDOT program
      structure and function. Programs that paid their CBDOT providers tended to differ
      from unpaid programs based on all of these features. CBDOT programs in which
      providers received financial reward had success rates of 85.7 versus 77.6% in
      programs without financial reward for providers. This difference was not
      statistically significant. CBDOT programs fall into two major archetypes, which
      differ in their structure and possibly in their outcomes.

PMID- 19760494
TI  - Using support vector machine combined with post-processing procedure to improve
      prediction of interface residues in transient complexes.
AB  - Reliable prediction of interface residues in transient complexes remains
      challenging, yet is highly desirable for the design of new drugs. The existing
      computational methods mainly rely on evolutionary information to identify these
      key residues, but evolutionary information may not be effective for the interface
      residues in all types of transient complexes, such as antigen-antibody complexes.
      Herein we combined B-factor with sequence profile and accessible surface area to
      predict these important residues using support vector machine (SVM). Furthermore,
      a post-processing method was developed to reduce the number of false positives
      recognized by SVM. The prediction results show that B-factor is an effective
      indicator for the interface residues in antigen-antibody complexes as well as
      those in other types of transient complexes. In addition, we found that the post
      processing procedure made an important contribution to further improve the
      prediction performance. Consequently, the proposed approach could provide new
      insight into accurately predicting interface residues in different types of
      transient complexes.

PMID- 19760495
TI  - Hydrophobic interactions stabilize the basigin-MCT1 complex.
AB  - Previous reports demonstrated that monocarboxylate transporter-1 (MCT1) interacts
      with Basigin. It was hypothesized that the two proteins interact via the
      transmembrane domain of Basigin, specifically through the glutamate residue
      within the domain. We therefore sought to test this hypothesis and determine
      which amino acids of the Basigin protein are necessary for the interaction with
      MCT1. Probes consisting of the full-length putative transmembrane domain, as well
      as small regions of the domain, were generated for use in ELISA binding assays
      using endogenous mouse MCT1. Site directed mutagenesis of candidate residues was
      performed and probes were generated for ELISA analyses to determine the specific
      residues involved. The data suggest that hydrophobic residues at the N- and C
      termini of the putative transmembrane domain of Basigin interact with MCT1, but
      the glutamate plays no role. The previously proposed hypothesis is partially
      correct, in that the putative transmembrane domain of Basigin does interact with
      MCT1.

PMID- 19760496
TI  - Recontacting patients who have tested negative for BRCA1 and BRCA2 mutations:
      how, who and why?

PMID- 19760497
TI  - A cross sectional study exploring factors impacting recruitment of African
      American college students into the genetic counseling profession.
AB  - African Americans account for about 12.7% of the United States population, but
      only 1% of the National Society of Genetic Counselors' membership identifies as
      African American. Since individuals often seek health care from providers sharing
      similar backgrounds, training genetic counselors from diverse backgrounds is
      critical. Psychology and biology students (N=552) at four universities completed
      a self-administered online survey assessing the influence of genetic counseling
      awareness, demographics, and career decisions on students' interest in pursuing
      genetic counseling as a career. More African Americans (83%) than Caucasians
      (62%) reported having chosen a career (p< or = .001). Of the 65% of students who
      indicated interest in the career description of genetic counseling, fewer African
      Americans (50%) than Caucasians (74%) had heard of genetic counseling (p< or =
      .001). Specific strategies to overcome recruiting barriers such as early career
      selection and lack of awareness of the genetic counseling career among African
      Americans are suggested.

PMID- 19760498
TI  - Epidural analgesia and risks of cesarean and operative vaginal deliveries in
      nulliparous and multiparous women.
AB  - Objective is to examine the effect of epidural analgesia in first stage of labor
      on occurrence of cesarean and operative vaginal deliveries in nulliparous women
      and multiparous women without a previous cesarean delivery. Design of the
      Prospective cohort study. Prenatal care was received at 12 free-standing health
      centers, 7 private physician offices, or 2 hospital-based clinics; babies were
      delivered at a free standing birth center or at 3 hospitals, all in San Diego,
      CA. This study of 2,052 women used data from the San Diego Birth Center Study
      that enrolled women between 1994 and 1996 to compare the birthing management of
      the collaborative Certified Nurse Midwife-Medical Doctor Model with that of the
      traditional Medical Doctor Model. Main Outcome Measures of the Cesarean or
      operative vaginal deliveries. After adjusting for differences between women who
      used and those who did not use epidural analgesia in 1st stage of labor, epidural
      use was associated with a 2.5 relative risk (95% CI: 1.8, 3.4) for operative
      vaginal delivery in nulliparous women, and a 5.9 relative risk (95% CI: 3.2,
      11.1) in multiparous women. Epidural use was associated with a 2.4 relative risk
      (95% CI: 1.5, 3.7) for cesarean delivery in nulliparous women, and a 1.8 relative
      risk (95% CI: 0.6, 5.3) in multiparous women. Epidural anesthesia increases the
      risk for operative vaginal deliveries in both nulliparous and multiparous women,
      and increases risk for cesarean deliveries in nulliparous more so than in
      multiparous women.

PMID- 19760500
TI  - Heart rate recovery predicts memory performance in older adults.
AB  - The current study examined cardiovascular reactivity and recovery during memory
      testing in a sample of 28 younger and 28 older adults. Heart rate (HR) levels
      were measured before, during, and after a memory test (word list recall).
      Contrary to prediction, older adults did not have a blunted cardiovascular
      response to memory tasks compared to younger adults. Word list recall performance
      was predicted by both Age and an Age x HR recovery interaction. As expected,
      younger adults performed better on the word list task than older adults. In
      addition, older adults with better posttest HR recovery performed significantly
      better than older adults with poor posttest HR recovery, whereas HR recovery
      differences in younger adults were inconsequential. These relationships were not
      affected by subjective appraisals of anxiety and task difficulty. Overall,
      cardiac dysregulation, seen here as low HR recovery, represents an important,
      potentially modifiable, factor in memory performance in older adults. In addition
      to being beneficial to overall health, interventions designed to help older
      adults regulate their HR responses may help offset certain memory declines.

PMID- 19760501
TI  - A novel antiestrogen agent Shikonin inhibits estrogen-dependent gene
      transcription in human breast cancer cells.
AB  - Shikonin (SK) has been isolated and identified as a key bioactive component in an
      herbal plant, Shikon (gromwell). In this study, we investigated antiestrogen
      activity of SK in breast cancer cells. In human breast cancer cells, we observed
      that treatment with SK inhibits tumor cell growth in estrogen receptor alpha
      (ERalpha)-positive, but not ERalpha-negative breast cancer cells. Estrogen
      dependent cell growth was inhibited by co-treatment with SK. A potential
      molecular mechanism by which SK inhibits estrogen action was explored. We found
      that SK has no effect on ERalpha mRNA expression, but decreases its protein
      level. This effect is associated with an increase in ubiquitinated ERalpha for
      degradation. Our results suggest that SK downregulates ERalpha protein through a
      proteasome-mediated pathway. We also found that the treatment with SK inhibits
      estrogen-induced estrogen response elements reporter gene activity. Furthermore,
      SK inhibits recruitment of ERalpha at the estrogen-dependent gene promoters, and
      subsequently suppresses gene expression. Finally, co-treatment with SK enhanced
      sensitivity of breast cancer cells to endocrine therapy. Collectively, our
      studies suggested that SK has a potential for antihormone therapy in ERalpha
      positive breast cancer cells, and should serve as a target for new drug
      developments.

PMID- 19760502
TI  - Transactivation of ErbB-2 induced by tumor necrosis factor alpha promotes NF
      kappaB activation and breast cancer cell proliferation.
AB  - Tumor necrosis factor alpha (TNFalpha) is a pleiotropic cytokine which, acting
      locally, induces tumor growth. Accumulating evidence, including our findings,
      showed that TNFalpha is mitogenic in breast cancer cells in vitro and in vivo. In
      the present study, we explored TNFalpha involvement on highly aggressive ErbB-2
      overexpressing breast cancer cells. We found that TNFalpha induces ErbB-2
      phosphorylation in mouse breast cancer C4HD cells and in the human breast cancer
      cell lines SK-BR-3 and BT-474. ErbB-2 phosphorylation at Tyr877 residue was
      mediated by TNFalpha-induced c-Src activation. Moreover, TNFalpha promoted ErbB
      2/ErbB-3 heterocomplex formation, Akt activation and NF-kappaB transcriptional
      activation. Inhibition of ErbB-2 by addition of AG825, an epidermal growth factor
      receptor/ErbB-2-tyrosine kinase inhibitor, or knockdown of ErbB-2 by RNA
      interference strategy, blocked TNFalpha-induced NF-kappaB activation and
      proliferation. However, the humanized monoclonal antibody anti-ErbB-2 Herceptin
      could not inhibit TNFalpha ability to promote breast cancer growth.
      Interestingly, our work disclosed that TNFalpha is able to transactivate ErbB-2
      and use it as an obligatory downstream signaling molecule in the generation of
      mitogenic signals. As TNFalpha has been shown to be present in the tumor
      microenvironment of a significant proportion of human infiltrating breast
      cancers, our findings would have clinical implication in ErbB-2-positive breast
      cancer treatment.

PMID- 19760503
TI  - Absence of chromosome 17 polysomy in breast cancer: analysis by CEP17 chromogenic
      in situ hybridization and multiplex ligation-dependent probe amplification.
AB  - Amplification of the HER2 gene, present in 15-30% of breast carcinomas,
      correlates with poor outcome and is an indication for treatment with trastuzumab.
      Standard testing methods for HER2 amplification are fluorescence (FISH) or
      chromogenic in situ hybridization (CISH). In FISH/CISH scoring, correction for
      chromosome 17 polysomy is believed to be critical for determination of true HER2
      amplification as opposed to increased chromosome 17 copy number. The term
      "polysomy 17" is widely used and defined as > or =3 copies of the chromosome 17
      centromere (probe CEP17, D17Z1). Thus, the centromere is assumed to be
      representative for the entire chromosome. This study aimed to investigate the
      frequency of polysomy 17 and its association with HER2 amplification in 111
      invasive breast cancer patients by CEP17 CISH and by copy number analysis of a
      set of 17 genes along chromosome 17 using multiplex ligation-dependent probe
      amplification (MLPA).Chromosome 17 usually showed a complex pattern of gains and
      losses by MLPA, unrelated to the copy number status of the centromere. Increase
      in centromere 17 copy number (denoted "polysomy 17"), as assessed by CEP17 CISH,
      was found in 19% of the patients. Of these patients, 60% also showed
      amplification of HER2 measured by MLPA. However, none of the 111 patients showed
      a true polysomy of chromosome 17 by MLPA. Only two patients (1.8%) had a possible
      gain of 17q. Amplification of 17p was not found in any of the patients, although
      a possible loss of 17p was found in one patient. In conclusion, this extensive
      analysis of amplicons along chromosome 17 shows that true polysomy of chromosome
      17, either of the whole chromosome or of the short or the long arm, is very rare
      in invasive breast cancer. Abnormal CEP17 copy numbers may therefore actually
      stem from high level gains or amplification of CEP17 regardless of copy number
      gains of the short and long arms of chromosome 17 and, at least in some cases,
      correction with CEP17 probes may provide misleading HER2 gene status assessment
      results.

PMID- 19760504
TI  - Feasible stability region in the frontal plane during human gait.
AB  - The inability to adequately control the motion of the center of mass (COM) in the
      frontal plane may result in a loss of balance causing a sideways fall during
      human gait. The primary purposes of this study were (1) to derive the feasible
      stability region (FSR) in the mediolateral direction, and (2) to compare the FSR
      with the COM motion state taken from 193 trials among 39 young subjects at
      liftoff during walking at different speeds. The lower boundary of the FSR was
      derived, at a given initial COM location, as the minimum rightward COM velocity,
      at liftoff of the left foot, required to bring the COM into the base of support
      (BOS), i.e., the right (stance) foot, as the COM velocity diminishes. The upper
      boundary was derived as the maximum rightward COM velocity, beyond which the left
      foot must land to the right of the right foot (BOS) in order to prevent a fall.
      We established a 2-link human model and employed dynamic optimization to estimate
      these threshold values for velocity. For a range of initial COM positions,
      simulated annealing algorithm was used to search for the threshold velocity
      values. Our study quantified the extent to which mediolateral balance can still
      be maintained without resorting to a crossover step (the left foot lands to the
      right of the BOS) for balance recovery. The derived FSR is in good agreement with
      our gait experimental results.

PMID- 19760505
TI  - Health promotion and disease prevention: logically different conceptions?
AB  - The terms "health promotion" and "disease prevention" refer to professional
      activities. But a "health promoter" has also come to denote a profession, with an
      alternative agenda compared to that of traditional public health work, work that
      by some is seen to be too medically oriented, too reliant upon prevention, risk
      elimination and health-care. But is there really a sharp distinction between
      these activities and professions? The main aim of the paper is to investigate if
      these concepts are logically different, or if they are just two extremes of one
      dimension. The central concepts, health promotion and disease prevention, are
      defined, and it is concluded that health promotion and disease prevention are
      logically distinct concepts, although they are conceptually related through a
      causal connection. Thus, logically, it is possible to promote health without
      preventing disease, even if this is not so common, in practice, but it is not
      possible to prevent disease without promoting health. Finally, most health
      promoting interventions target basic health, not manifest health, and often also
      thereby reduce future disease.

PMID- 19760506
TI  - Determinants of physical activity in Singaporean adolescents.
AB  - BACKGROUND: An understanding of the factors that influence physical activity
      behavior is an important prerequisite for the design and implementation of
      physical activity interventions in adolescents. To date, no studies have
      investigated the factors that influence physical activity participation in
      Singaporean adolescents. PURPOSE: The purpose of this study was to identify the
      psychosocial and environmental factors that influence physical activity in a
      representative sample of Singaporean adolescents (N = 1,814, 919 boys, 895 girls,
      mean age 14.4 +/- 1.1 years). METHODS: Participants completed the Three-Day
      Physical Activity Recall and a questionnaire measuring hypothesized psychosocial
      and environmental correlates of physical activity. RESULTS: Hierarchical
      regression revealed self-efficacy, enjoyment of physical activity, parental
      support, and participation in sport teams to be significant correlates of
      physical activity. CONCLUSION: Interventions promoting physical activity in
      Singaporean adolescents should aim to increase self-efficacy perceptions by
      offering enjoyable, developmentally appropriate physical activity options that
      promote mastery and adopt policies that increase parental support and awareness
      of community physical activity programs.

PMID- 19760507
TI  - Males of the two-spotted spider mite attempt to copulate  with mated females:
      effects of double mating on fitness  of either sex.
AB  - In Tetranychus urticae (Acari: Tetranychidae), when the intervals between first
      and second copulation are more than 24 h, only the first copulation is effective
      for females. Therefore, adult males should copulate only with virgin females, but
      not with females that copulated more than 1 day ago. Indeed, T. urticae males
      preferred virgin females to mated females under dual choice conditions. In the
      absence of virgin females, however, 60% of males copulated with mated females (n
      = 30). Therefore, the effects of male copulation behaviour on male and mated
      female fitness were examined, respectively. Since T. urticae is arrhenotokous
      (i.e., only daughters have genes derived from their father), the proportion of
      females among the offspring was used as an index of male fitness. After males had
      lived with/without a mated female, the males were allowed to copulate with a
      virgin female. The proportion of females among the offspring did not differ
      between males with and without a female. On the other hand, when mated females
      lived with an adult male, their egg production was lower than mated females
      without a male. These results suggest that males do not seem to obtain fitness
      benefit from the copulation behaviour and that mated females incur a fitness cost
      due to the male behaviour.

PMID- 19760508
TI  - The role of volatiles in aggregation and host-seeking of the haematophagous
      poultry red mite Dermanyssus gallinae (Acari: Dermanyssidae).
AB  - Infestations with ectoparasitic poultry red mites (Dermanyssus gallinae) pose an
      increasing threat to poultry health and welfare. Because of resistance to
      acaricides and higher scrutiny of poultry products, alternative and
      environmentally safe management strategies are warranted. Therefore, we
      investigated how volatile cues shape the behavior of D. gallinae and how this
      knowledge may be exploited in the development of an attract-and-kill method to
      control mite populations. A Y-tube olfactometer bio-assay was used to evaluate
      choices of mites in response to cues related to conspecific mites as well as
      related to their chicken host. Both recently fed and starved mites showed a
      strong preference (84 and 85%, respectively) for volatiles from conspecific, fed
      mites as compared to a control stream of clean air. Mites were also significantly
      attracted to 'aged feathers' (that had remained in the litter for 3-4 days), but
      not to 'fresh feathers'. Interestingly, an air stream containing 2.5% CO(2),
      which mimics the natural concentration in air exhaled by chickens, did attract
      fed mites, but inhibited the attraction of unfed mites towards volatiles from
      aged feathers. We conclude that both mite-related cues (aggregation pheromones)
      and host-related cues (kairomones) mediate the behavior of the poultry mite. We
      discuss the options to exploit this knowledge as the 'attract' component of
      attract-and-kill strategies for the control of D. gallinae.

PMID- 19760509
TI  - Complex meiotic configuration of the holocentric chromosomes: the intriguing case
      of the scorpion Tityus bahiensis.
AB  - Mitotic and meiotic chromosomes of Tityus bahiensis were investigated using light
      (LM) and transmission electron microscopy (TEM) to determine the chromosomal
      characteristics and disclose the mechanisms responsible for intraspecific
      variability in chromosome number and for the presence of complex chromosome
      association during meiosis. This species is endemic to Brazilian fauna and
      belongs to the family Buthidae, which is considered phylogenetically basal within
      the order Scorpiones. In the sample examined, four sympatric and distinct diploid
      numbers were observed: 2n = 5, 2n = 6, 2n = 9, and 2 = 10. The origin of this
      remarkable chromosome variability was attributed to chromosome fissions and/or
      fusions, considering that the decrease in chromosome number was concomitant with
      the increase in chromosome size and vice versa. The LM and TEM analyses showed
      the presence of chromosomes without localised centromere, the lack of chiasmata
      and recombination nodules in male meiosis, and two nucleolar organiser regions
      carrier chromosomes. Furthermore, male prophase I cells revealed multivalent
      chromosome associations and/or unsynapsed or distinctly associated chromosome
      regions (gaps, less-condensed chromatin, or loop-like structure) that were
      continuous with synapsed chromosome segments. All these data permitted us to
      suggest that the chromosomal rearrangements of T. bahiensis occurred in a
      heterozygous state. A combination of various factors, such as correct disjunction
      and balanced segregation of the chromosomes involved in complex meiotic pairing,
      system of achiasmate meiosis, holocentric nature of the chromosomes, population
      structure, and species dispersion patterns, could have contributed to the high
      level of chromosome rearrangements present in T. bahiensis.

PMID- 19760510
TI  - NDRG1 and CRK-I/II are regulators of endothelial cell migration under
      Intermittent Hypoxia.
AB  - Intermittent Hypoxia (IH) that develops in neovascularized solid tumours has been
      described to positively influence the tumour growth by modulating the behaviour
      of cancer cells as well as of endothelial cells. However, the molecular
      mechanisms regulated by IH still remain poorly understood. In this work, the
      effects of IH were investigated on endothelial cells by a proteomic approach.
      Protein abundance variations were studied using fluorescent 2D-Differential in
      Gel Electrophoresis (2D-DIGE). Amongst the proteins of which the abundance varied
      under IH, NDRG1 and CRK-I/II were identified by mass spectrometry. These proteins
      have already been described to influence cancer cell migration as well as the
      angiogenic processes in solid tumours. Since an increase in endothelial cell
      migration under IH was evidenced in our previous work, the involvement of NDRG1
      and CRK-I/II proteins in endothelial cell migration under IH was determined by
      silencing the expression of both proteins using siRNA. The results revealed that
      NDRG1 and CRK-I/II are indeed regulators of endothelial cell migration under
      intermittent hypoxia: silencing of CRK-I/II resulted in an increase in
      endothelial cell migration, whereas the invalidation of NDRG1 decreased it. These
      results give news insight regarding the effects of IH on endothelial cell
      migration and hence on neoangiogenesis.

PMID- 19760511
TI  - Integrated case learning: teaching clinical reasoning.
AB  - Learning how to 'think like doctors' can be difficult for undergraduate medical
      students in their early clinical years. Our model of collaborative Integrated
      Case Learning (ICL) and simulated clinical reasoning aims to address these
      issues. Taking a socio-cultural perspective, this study investigates the
      reflective learning interactions and practices of clinical thinking that emerged
      in the ICL environment. We also explore how third year medical students perceived
      their ICL experiences in relation to the clinical situations encountered in the
      hospital setting. The context for the inquiry is a rural Clinical School in North
      West Victoria, Australia. We used a qualitative case study methodology following
      eight third-year medical students over an academic year. Individual and group
      interviews were conducted, together with observations and document/artefact
      analysis. Data was analysed using content and narrative methods. The ICL program
      was well received. Findings suggest that the group-based, simulated clinical
      reasoning process appears to help undergraduate medical students to rehearse,
      articulate and question their clinical decision-making pathways. We argue that
      the ICL process offers a professionally challenging, but supportive group
      learning 'space' for students to practise what it might mean to 'think', 'talk'
      and 'perform' like doctors in real settings. The ICL environment also appears to
      create a connective bridge between the 'classroom' and clinical practice.

PMID- 19760512
TI  - Protective effect of Antrodia camphorata on bladder ischemia/reperfusion injury.
AB  - INTRODUCTION: Obstructive bladder dysfunction is directly related to
      ischemia/reperfusion injury characterized by damage to nerves, synapses and
      smooth muscle cells within the bladder wall. Antrodia Camphorata (AC) has
      significant antioxidant, antiinflammatory and cell-cycle inhibition properties.
      The specific aim of this study was to evaluate whether orally administered AC can
      protect rabbit bladders from the progressive dysfunctions induced by bilateral
      ischemia/reperfusion (I/R). METHODS: Twenty-four male NZW rabbits were separated
      into 4 groups of 6 animals each. Rabbits in groups 1 and 2 were fed Antrodia
      Camphorata (AC) suspensions; those in groups 3 and 4 received vehicle. Each
      rabbit in groups 2 and 4 were subjected to in vivo bilateral ischemia for 2 h and
      then allowed to recover for 1 week. The rabbits in groups 1 and 3 received sham
      operation and served as control groups. Cystometry, contractile responses to
      field stimulation, carbachol, ATP and KCl were determined. Biochemical and immuno
      histochemical studies were also performed. RESULTS: I/R resulted in decreased
      compliance, decreased contractile responses, decreased nerve density, and
      increased apoptosis. AC pretreatment of rabbits subjected to I/R significantly
      protected the bladder from all contractile, biochemical, and structural
      dysfunctions resulting in significantly improved bladder.

PMID- 19760513
TI  - Modified ureteroneocystostomy in kidney transplantation to facilitate endoscopic
      management of subsequent urological complications.
AB  - OBJECTIVES: Urological complications in kidney transplant patients are among
      serious complications. Endourology has allowed for a less-invasive approach to
      dealing with these transplant complications. Access to the upper urinary tract in
      traditionally anterior extravesical ureteroneocystostomy is usually difficult if
      not impossible. MATERIALS AND METHODS: We evaluated the results of renal
      transplantation comparing two techniques of anterior extravesical
      ureteroneocystostomy (AEVUNC) and posterolateral extravesical
      ureteroneocystostomy (PLEVUNC). A total of 120 transplant recipients were
      randomized to either PLEVUNC (group 1, n = 61) or AEVUNC (group 2, n = 59)
      techniques. Ureteral and nonureteral complications were compared at 36- to 51
      month follow-up. The data regarding successful ureteroscopy were also gathered.
      RESULTS: The PLEVUNC group had a urological complication rate of 27.9%, which did
      not significantly differ from those in AEVUNC group (26.1%) (P = 0.1). In the
      PLEVUNC group, 1- and 3-year graft survivals were 92.6 and 85.2%, respectively,
      whereas in the AEVUNC group they were 92.3 and 82.7%, respectively (P = 0.08).
      There were no significant differences between urinary tract infections, delayed
      graft function, and chronic allograft nephropathy between the two groups (P =
      0.1, 0.1 and 0.08, respectively). Three patients (5.6%) in PLEVUNC group and 1
      (1.9%) in AEVUNC group developed immediate postoperative hydronephrosis after
      removal of ureteral stent (P = 0.04). Successful ureteroscopy was achieved in 52
      (96.3%), and 39 (75%), of patients in PLEVUNC and AEVUNC groups, respectively (P
      = 0.001). CONCLUSIONS: Easy and safe access to the upper urinary tract in
      transplant recipients can be achieved using a PLEVUNC technique. This facilitates
      the endoscopic procedures in the case of urological complications and disorders.

PMID- 19760514
TI  - Lactobacillus collinoides JCM1123(T): effects on mouse plasma cholesterol and
      isoflavonoids in the caecum.
AB  - The effects of Lactobacillus collinoides JCM1123(T) on plasma cholesterol levels,
      isoflavonoids in the caecum and faecal flora were assessed in adult mice. L.
      collinoides JCM1123(T) altered the equol production status in in vitro incubation
      of daidzein with faecal flora of mice. In in vivo investigation, mice were fed an
      AIN-93M purified diet for 13 days, and then randomly divided into two groups of
      seven animals each. All mice were fed an AIN-93M diet for 6 days; then the diet
      was replaced with a 0.05% daidzein diet, the mice received a 0.05% daidzein diet
      for 4 days. Two groups of mice were administered either L. collinoides JCM1123(T)
      (the experimental group) or a physiological saline solution (the control group)
      daily for 10 days and dissection was performed on the following day. The total
      plasma cholesterol concentration was significantly higher in the control group
      than in the experimental group. The amount of daidzein present in the caecum was
      significantly higher in the control group than in the experimental group.
      Significantly higher numbers of lactobacilli were observed in the experimental
      group than in the control group. Our data suggest that the administration of L.
      collinoides is likely to influence the metabolism of isoflavonoids and endogenous
      cholesterol via changes in the gastrointestinal environment.

PMID- 19760515
TI  - Determination of genetic diversity among Indian isolates of Rhizoctonia
      bataticola causing dry root rot of chickpea.
AB  - Genetic diversity among 27 isolates (23 from chickpea and 4 from other host
      crops) of Rhizoctonia bataticola representing 11 different states of India was
      determined by random amplified polymorphic DNA (RAPD), internal transcribed
      spacer restriction fragment length polymorphism (ITSRFLP) and ITS sequencing. The
      isolates showed variability in virulence test. Unweighted paired group method
      with arithmetic average cluster analysis was used to group the isolates into
      distinct clusters. The clusters generated by RAPD grouped all the isolates into
      six categories at 40% genetic similarity. High level of diversity was observed
      among the isolates of different as well as same state. Some of the RAPD (OPN 4,
      OPN 12, and OPN 20) markers clearly distinguished majority of the isolates into
      the area specific groups. The ITS I, 5.8 rDNA and ITS II regions of 11 isolates
      representing different RAPD groups were amplified with primers ITS 1 and ITS 4
      and digested with seven restriction enzymes. The restriction enzymes DraI, MboI,
      RsaI, and AluI were found to be suitable for differentiating the isolates into
      five categories by showing isolate specific ITS-RFLP patterns. The isolates were
      variable in their nucleotide sequences of the ITS regions. This is the first
      study on genetic diversity among chickpea isolates of R. bataticola.

PMID- 19760516
TI  - Spectroscopy to improve identification of vulnerable plaques in cardiovascular
      disease.
AB  - Many apparent healthy persons die from cardiovascular disease, despite major
      advances in prevention and treatment of cardiovascular disease. Traditional
      cardiovascular risk factors are able to predict cardiovascular events in the long
      run, but fail to assess current disease activity or nearby cardiovascular events.
      There is a clear relation between the occurrence of cardiovascular events and the
      presence of so-called vulnerable plaques. These vulnerable plaques are
      characterized by active inflammation, a thin cap and a large lipid pool.
      Spectroscopy is an optical imaging technique which depicts the interaction
      between light and tissues, and thereby shows the biochemical composition of
      tissues. In recent years, impressive advances have been made in spectroscopy
      technology and intravascular spectroscopy is able to assess the composition of
      plaques of interest and thereby to identify and actually quantify plaque
      vulnerability. This review summarizes the current evidence for spectroscopy as a
      measure of plaque vulnerability and discusses the potential role of intravascular
      spectroscopic imaging techniques.

PMID- 19760517
TI  - Erythematous oral candidiasis in patients with controlled type II diabetes
      mellitus and complete dentures.
AB  - Diabetes mellitus (DM) is a systemic condition characterized by a deficient sugar
      metabolism, which affects the immune system and favors the development of yeasts.
      The aim of the present study was to perform biochemical, morphological, exoenzyme
      analyses of Candida species and the molecular identification (DNA) of C. albicans
      in patients with type II diabetes mellitus. The exoenzyme quantification was
      compared to non-diabetic patients as controls. Two hundred and seventy-four
      patients who make use of complete dentures were evaluated, 28 of whom had
      diabetes and erythematous oral candidiasis. Other thirty patients presented the
      same clinical feature but without diabetes. Samples were isolated for biochemical
      identification (auxonogram), morphological identification (production of germ
      tubes) and PCR molecular identification (DNA). The capability of the Candida
      samples in producing phospholipases and proteinases was also determined. The
      diabetic patients had a greater diversity of Candida species (Fischer's exact
      test, P = 0.04). The production of proteinases by C. albicans in patients with
      diabetes was greater than in the control group (unpaired "t" test P < 0.003).
      However, there was no difference between groups for phospholipase production
      (unpaired "t" test P > 0.05). It was concluded that patients with controlled DM
      exhibited systemic conditions predisposing C. albicans proteinase increased
      production.

PMID- 19760518
TI  - A study on MSH2 and MLH1 mutations in hereditary nonpolyposis colorectal cancer
      families from the Basque Country, describing four new germline mutations.
AB  - Hereditary non-polyposis colorectal cancer (HNPCC) or Lynch syndrome underlies
      between 2 and 5% of all colorectal cancer. It is inherited as an autosomal
      dominant condition due to mutations in the mismatch repair genes. Fifty-four non
      related index cases, 21 of them fulfilling Amsterdam criteria I or II, were
      studied. Ten (10/21 = 47.6%) different pathological mutations were found in this
      group, two of which had not previously been reported--one in MLH1 and the other
      in MSH2-. In the remaining patients, we also found another family with one of
      these new mutations, and four additional changes, two of which were also new--a
      pathological change in MSH2 and a second change of uncertain significance in MLH1
      , while the other two changes had already been reported. Of all mutations, eight
      were found in MSH2 (8/15 = 53.3%) and seven in MLH1 (7/15 = 46.6%), suggesting a
      slightly greater involvement of MSH2 in HNPCC than MLH1 in our population, in
      contrast to the results reported by other authors.

PMID- 19760519
TI  - Letter to the Editor: resonance assignment of SlyD from E. coli.
AB  - SlyD from Escherichia coli is a peptidyl-prolyl cis-trans isomerase involved in
      [Ni-Fe] hydrogenase metallocentre assembly in bacteria. We present here the
      backbone and side chain assignments for E. coli SlyD.

PMID- 19760520
TI  - The role of VE-cadherin in osteosarcoma cells.
AB  - Osteosarcoma cells can generate vasculogenic-like, patterned networks to obtain
      nutrients and oxygen, which mimic some function of endothelial-like cells and
      facilitate tumor malignant progress. These cells also express vascular
      endothelial-cadherin (VE-cadherin), which is generally accepted as a strictly
      endothelial-specific transmembrane protein. However, its role is still relatively
      obscure in osteosarcoma cells. So we inhibit the VE-cadherin gene expression with
      siRNA in osteosarcoma cells (MG63), and culture those cells in three-dimensional
      medium, containing Type I collagen or Matrigel, to observe the role of VE
      cadherin. Western blotting analysis show that sequence-specific siRNA can
      significantly decrease the expression of VE-cadherin in MG63 cell. After
      knockdown of VE-cadherin, osteosarcoma cells can't induced angiogenic sprout and
      form osteosarcoma-generated, endothelial-like networks. Our data indicate that VE
      cadherin may be a positive and specific regulator not only in angiogenesis, but
      also in vasculogenic mimicry of osteosarcoma cells. And it can be considered as a
      new prospective option in the combining treatment of aggressive tumor with highly
      vascularity, including osteosarcoma.

PMID- 19760521
TI  - Editorial note--Darwin and the origin of life.

PMID- 19760522
TI  - Translin-associated factor X gene (TSNAX) may be associated with female major
      depressive disorder in the Japanese population.
AB  - Several investigations have reported that the translin-associated factor X gene
      (TSNAX)/disrupted-in-schizophrenia-1 gene (DISC1) was associated with major
      psychiatric disorders including schizophrenia, bipolar disorder (BP), and major
      depressive disorder (MDD). TSNAX is located immediately upstream of DISC1, and
      has been shown to undergo intergenic splicing with DISC1. It thus may also be
      influenced by translocation. To our knowledge, there are no reported gene-based
      association analyses between TSNAX and mood disorders in the Japanese population.
      We conducted a case-control study of Japanese samples (158 bipolar patients, 314
      major depressive disorder patients, and 811 controls) with three tagging SNPs in
      TSNAX, selected using HapMap database. In addition, we performed an association
      analysis between TSNAX and the efficacy of fluvoxamine treatment in 120 Japanese
      patients with MDD. The MDD patients in this study had scores of 12 or higher on
      the 17 items of the Structured Interview Guide for Hamilton Rating Scale for
      Depression (SIGH-D). We defined a clinical response as a decrease of more than
      50% in baseline SIGH-D within 8 weeks, and clinical remission as an SIGH-D score
      of less than 7 at 8 weeks. We found an association between rs766288 in TSNAX and
      female MDD in the allele/genotype analysis. However, we did not find any
      association between TSNAX and BP or the fluvoxamine therapeutic response in MDD
      in the allele/genotype analysis or haplotype analysis. Our results suggest that
      rs766288 in TSNAX may play a role in the pathophysiology of female MDD in the
      Japanese population. A replication study using larger samples may be required for
      conclusive results, since our sample size was small.

PMID- 19760523
TI  - Transgenic rice plants expressing a modified cry1Ca1 gene are resistant to
      Spodoptera litura and Chilo suppressalis.
AB  - Nucleotide sequence encoding the truncated insecticidal Cry1Ca1 protein from
      Bacillus thuringiensis was extensively modified based on the codon usage of rice
      genes. The overall G + C contents of the synthetic cry1Ca1 coding sequence were
      raised to 65% with an additional bias of enriching for G and C ending codons as
      preferred by monocots. The synthetic gene was introduced into the Chinese
      japonica variety, Xiushui 11, by Agrobacterium-mediated transformation.
      Transgenic rice plants harboring this gene were highly resistant to Chilo
      suppressalis and Spodoptera litura larvae as revealed by insect bioassays. High
      levels of Cry1Ca1 protein were obtained in the leaves of transgenic rice, which
      were effective in achieving 100% mortality of S. litura and C. suppressalis
      larvae. The levels of Cry1Ca1 expression in the leaves of these transgenic plants
      were up to 0.34% of the total soluble proteins. The larvae of C. suppressalis and
      S. litura could consume a maximum of 1.89 and 4.89 mm2 of transgenic leaf area
      whereas the consumption of nontransgenic leaves by these larvae was significantly
      higher; 58.33 and 61.22 mm2, respectively. Analysis of R1 transgenic plants
      indicated that the cry1Ca1 was inherited by the progeny plants and provided
      complete protection against C. suppressalis and S. litura larvae.

PMID- 19760524
TI  - Two "childhood" malignancies in an elderly individual: a case report and
      discussion.
AB  - Rhabdomyosarcoma (RMS) is the most common soft-tissue tumor in childhood, but is
      extremely rare in elderly. We present a rare case of cardiac RMS, which developed
      1 year after the diagnosis and management of acute lymphoblastic leukemia in a 68
      year-old female. The occurrence of such phenomena is intriguing, especially in an
      individual without prior history of malignancy at a younger age. Through the
      review of the existing literature, we attempt to approach the pathogenesis and
      clinical manifestations of this rare clinical entity.

PMID- 19760525
TI  - Delusion and confabulation: mistakes of perceiving, remembering and believing.
AB  - This paper adopts an inclusive approach to the relationship between delusion and
      confabulation, according to which some symptoms might qualify as both delusional
      and confabulatory. Our initial focus is on the cardinal signs of delusions:
      incomprehensibility, incorrigibility, and subjective conviction. Setting aside
      post hoc (or secondary) confabulations-plausible rationalisations that might be
      generated by nonpathological belief formation processes-we focus on spontaneous
      memory-based confabulations which, we suggest, conform to the characterisation of
      delusions. After considering current accounts of the role of experience in
      delusion formation, we propose that spontaneous confabulations are located at (or
      towards) the "received" end of a "received-reflective" spectrum of delusions: the
      spontaneous confabulator simply receives and endorses as genuine the content of
      an apparent-yet implausible-memory experience. Underlying both spontaneous
      confabulations and other received delusions, we propose, is an inability to
      inhibit the prepotent tendency to upload and maintain experiential content
      (mnemonic or perceptual) into belief.

PMID- 19760526
TI  - Olive oil adulterated with hazelnut oils: simulation to identify possible risks
      to allergic consumers.
AB  - According to European Union Regulation EC 1531/2001, olive oil labelled as "extra
      virgin" should be cold-pressed and contain no refined oil or oil from other
      oleaginous seeds or nuts. Adulteration of extra virgin olive oil (EVOO) with
      hazelnut oil (HAO) is a serious concern both for oil suppliers and consumers. The
      high degree of similarity between the two fats complicates the detection of low
      percentages of HAO in EVOO. Many analytical approaches have been developed in
      recent years to trace HAO in EVOO, principally based on chromatographic analyses,
      differential scanning calorimetry or nuclear magnetic resonance. In addition
      adulteration of EVOO with HAO may introduce hazelnut-derived allergens. The aim
      of this work was to analyse the protein and allergen content of EVOO
      intentionally spiked with raw cold-pressed HAO or solvent-extracted HAO. SDS-PAGE
      analysis confirmed the presence of hazelnut proteins in solvent-extracted HAO
      with molecular masses ranging 10-60 kDa. In contrast, cold-pressed HAO showed no
      traces of protein. In spiked EVOO, solvent-extracted HAO was still detectable at
      a 1% contamination level. Several bands on SDS-PAGE migrated at apparent
      molecular masses coinciding with known allergens, such as Cor a 1 (approximately
      17 kDa), Cor a 2 (approximately 14 kDa), Cor a 8 (approximately 12 kDa), oleosin
      (approximately 17 kDa) and Cor a 9 (approximately 60 kDa). MALDI-TOF MS analysis
      confirmed the presence of two oleosin isoforms and of Cor a 9. Immunoblotting
      demonstrated that an allergic patient with known reactivity to Cor a 1 and Cor a
      2 recognized a 17-kDa band in solvent-extracted HAO. In conclusion, we have shown
      that adulteration of extra virgin olive oil with solvent-extracted hazelnut oil
      can be traced by simple SDS-PAGE analysis, and that adulteration introduces a
      potential risk for hazelnut allergic patients.

PMID- 19760527
TI  - Occurrence of extractable ink residuals in packaging materials used in the Czech
      Republic.
AB  - Residues of printing ink components were determined in 94 samples of packaging
      materials commercially used in the Czech Republic for food packaging. The samples
      tested included printed polyethylene and polypropylene films, co-extruded and
      laminated films, paperboard beverages boxes, foils for thermo sealing of
      polystyrene cups, and polypropylene cups. Printing ink components were extracted
      with diethylether, then separated and determined using gas chromatography-mass
      spectrometry (GC/MS). Fifty compounds potentially originating from printing were
      isolated, identified and quantified. No acute health risk for consumers were
      identified, even though several findings of high levels of photo-initiators (e.g.
      in polyethylene terephthalate (PET) films for thermo sealing of polystyrene cups)
      as well as plasticizers (acetyl tributyl citrate, tributyl aconitate, 2
      butoxyethyl oleate and 2-ethylhexyl diphenyl phosphate in co-extruded films)
      indicate that their real migration into food and/or food simulants needs to be
      undertaken for a proper safety evaluation.

PMID- 19760528
TI  - Assessment of deoxynivalenol (DON) adsorbents and characterisation of their
      efficacy using complementary in vitro tests.
AB  - Deoxynivalenol (DON) is a prevalent and resistant mycotoxin found in cereals and
      related products. Adsorbents appear to provide an opportunity to decrease DON
      absorption in animals but, due to their specificity, it is very difficult to
      evaluate their actual efficacy. It is pointless to extrapolate results obtained
      with one mycotoxin to another and even to extrapolate results obtained in vitro
      in buffer to an in vivo situation. We carried out experiments to characterize the
      properties of potential DON adsorbents. Initial tests in buffer pH 7 allowed us
      to focus on six adsorbents: activated charcoal, cholestyramin, Saccharomyces
      cerevisiae mannans, algal beta-glycan, fungal beta-glycan and leguminous plant.
      The use of equilibrium sorption models suggested a non-saturated phenomenon and
      involved variable mechanisms according to the specific material. Subsequent tests
      with a Caco-2 cell model showed a high reduction in DON cytotoxicity on
      proliferative intestinal cells and DON absorption by differentiated intestinal
      cells when adsorbent was added (except for cholestyramin). Otherwise, values were
      not always in accordance with those obtained in buffer. Our work allowed us to
      identify five potential DON adsorbents and to propose a complementary in vitro
      test allowing improved determination of adsorbent properties.

PMID- 19760529
TI  - Reactions of heterosexual African American men to women's condom negotiation
      strategies.
AB  - This study describes responses of 172 single heterosexual African American men,
      ages 18 to 35, to condom negotiation attempts. Strategies used included reward,
      coercive, legitimate, expert, referent, and informational strategies, based on
      Raven's (1992) influence model. The purpose was (a) to identify strategies
      influencing participant acquiescence to request and (b) to identify predictors of
      participant compliance/refusal to comply with negotiation attempts. Participants
      viewed six videotape segments showing an actress, portrayed in silhouette,
      speaking to the viewer as a "steady partner." After each segment, participants
      completed measures of request compliance, positive and negative affect, and
      attributions concerning the model and themselves. No significant differences were
      found in men's ratings across all vignettes. However, differences in response
      existed across subgroups of individuals, suggesting that, although the strategy
      used had little impact on participant response, the act of suggesting condom use
      produced responses that differed across participant subgroups. Subgroups differed
      on levels of AIDS risk knowledge, sexually transmitted disease history, and
      experience with sexual coercion. Also, the "least willing to use" subgroup was
      highest in anger-rejection and least likely to make attributions of caring for
      partner. Effective negotiation of condom use with a male sexual partner may not
      be determined as much by specific strategy used as by partner characteristics.

PMID- 19760531
TI  - The right hand and the left hand of history.

PMID- 19760530
TI  - Selection of film clips and development of a video for the investigation of
      sexual decision making among men who have sex with men.
AB  - Experimental research on sexual decision making is limited, despite the public
      health importance of such work. We describe formative work conducted in advance
      of an experimental study designed to evaluate the effects of alcohol intoxication
      and sexual arousal on risky sexual decision making among men who have sex with
      men. In Study 1, we describe the procedures for selecting and validating erotic
      film clips (to be used for the experimental manipulation of arousal). In Study 2,
      we describe the tailoring of two interactive role-play videos to be used to
      measure risk perception and communication skills in an analog risky sex
      situation. Together, these studies illustrate a method for creating experimental
      stimuli to investigate sexual decision making in a laboratory setting. Research
      using this approach will support experimental research that affords a stronger
      basis for drawing causal inferences regarding sexual decision making.

PMID- 19760532
TI  - A Left Handed Compliment: A newly discovered, early nineteenth-century lithograph
      by John Lewis Marks.
AB  - A newly discovered, early nineteenth-century lithograph by John Lewis Marks (b.
      ca. 1795-1796, d. ca. 1857-1861), entitled A Left Handed Compliment, is
      described. In this humorous print a young boy is using his left hand to draw the
      face of an elderly woman who is his grandmother, and she is shocked at the boy's
      suggestion that he will, "just see if I can't touch off your old Phizog left
      handed". The source of the joke about the left-handed compliment is obscure, but
      more than likely it is sexual in origin. Glued to the verso of the print are
      early versions of two prints by Robert Seymour (1798-1836), the illustrator of
      Dickens' Pickwick Papers, suggesting a possible link between Marks and Seymour.
      From the hatch patterns on the Seymour engravings, it appears that Seymour may
      himself have been left-handed and perhaps therefore the butt of the joke. An
      alternative possibility is that Phizog is a reference to Dickens' later
      illustrator whose pseudonym was Phiz. It is also just conceivable that the young
      boy is Marks's own young son, Jacob. The print can be placed in the context of a
      scatological English vernacular humour that extends from Shakespeare through to
      Donald McGill and into the present day.

PMID- 19760533
TI  - Time to turn the other cheek? The influence of left and right poses on
      perceptions of academic specialisation.
AB  - The human face expresses emotion asymmetrically. Whereas the left cheek is more
      emotionally expressive, the right cheek appears more impassive, hence the
      appropriate cheek to put forward depends on the circumstance. Nicholls, Clode,
      Wood, and Wood (1999, Proceedings of the Royal Society (Section B), 266, 1517
      1522) demonstrated that people posing for family portraits offer the left cheek,
      whereas those posing as a Royal Society scientist favour the right. Given that
      the stereotypical representations of members of different academic disciplines
      differ markedly in their perceived openness and emotionality (e.g., "serious"
      scientist vs. "creative" writer), we reasoned that people may use cheek as a cue
      when determining a model's area of academic interest. Two hundred and nine
      participants (M=90, F=119) viewed pairs of left and right cheek poses, and made a
      forced-choice decision indicating which image depicted a Chemistry, Psychology or
      English student. Half the images were mirror-reversed to control for perceptual
      and aesthetic biases. Consistent with prediction, participants were more likely
      to select left cheek images for English students, and right cheek images for
      Chemistry students, irrespective of image orientation. The results confirm that
      determining the best cheek to put forward depends on your academic expertise: an
      impassive right cheek suggests hard science, whereas an emotive left cheek
      implies the arts. Psychology produced no left or right bias, consistent with its
      position as a discipline perpetually straddling the boundary between art and
      science.

PMID- 19760534
TI  - Motor simulation in verbal knowledge acquisition.
AB  - Recent research highlights the importance of motor processes for a wide range of
      cognitive functions such as object perception and language comprehension. It is
      unclear, however, whether the involvement of the motor system goes beyond the
      processing of information that is gathered through active action experiences and
      affects also the representation of knowledge acquired through verbal learning. We
      tested this prediction by varying the presence of motor interference (i.e.,
      squeezing a ball vs. oddball detection task) while participants verbally acquired
      functional object knowledge and examined the effects on a subsequent object
      detection task. Results revealed that learning of functional object knowledge was
      only impaired when participants performed an effector-specific motor task while
      training. The present finding of an effector-specific motor interference effect
      on object learning demonstrates the crucial role of the motor system in the
      acquisition of novel object knowledge and provides support for an embodied
      account to perception and cognition.

PMID- 19760535
TI  - Seeing with ears: Sightless humans' perception of dog bark provides a test for
      structural rules in vocal communication.
AB  - Prerecorded family dog (Canis familiaris) barks were played back to groups of
      congenitally sightless, sightless with prior visual experience, and sighted
      people (none of whom had ever owned a dog). We found that blind people without
      any previous canine visual experiences can categorize accurately various dog
      barks recorded in different contexts, and their results are very close to those
      of sighted people in characterizing the emotional content of barks. These
      findings suggest that humans can recognize some of the most important
      motivational states reflecting, for example, fear or aggression in a dog's bark
      without any visual experience. It is very likely that this result can be
      generalized to other mammalian species--that is, no visual experience of another
      individual is needed for recognizing some of the most important motivational
      states of the caller.

PMID- 19760536
TI  - What's on your mind: the influence of the contents of working memory on choice.
AB  - Information maintained in working memory (WM) has the potential to bias selective
      attention and limit executive attention. The current study assessed the influence
      of information in WM on the tasks one chooses to perform in a multitasking
      environment. Participants held either identities or locations in WM while
      performing voluntary task-switching trials on stimuli that did or did not match
      the information they were attempting to maintain. A bias toward performing the
      task associated with stimuli that had recently been encoded into WM was found.
      The results suggest that information in WM can influence choice within a
      multitasking environment.

PMID- 19760537
TI  - Cystic fibrosis.

PMID- 19760538
TI  - The clinical approach to lung disease in patients with cystic fibrosis.
AB  - There is strong evidence that early, aggressive therapy of lung disease leads to
      improved quality and quantity of life for patients with cystic fibrosis (CF). The
      treatment of pulmonary disease associated with CF is multifactorial, encompassing
      prophylaxis, aggressive treatment of infection, use of antiinflammatory agents,
      and treatment of severe complications. Chest physiotherapy on a regular basis,
      perhaps using new modalities that allow patient autonomy, is also crucial. This
      review covers the pathogenesis of CF lung disease and current approaches to
      therapy, highlighting guidelines recently published by the Cystic Fibrosis
      Foundation. Clinicians caring for patients with CF should maximize current
      therapies with the goal of preserving lung function until the time a more
      definitive curative or controller medication is developed. Empowering patients in
      the process of providing their own care is a key to achieving this goal.

PMID- 19760539
TI  - Diabetes mellitus and bone disease in cystic fibrosis.
AB  - Patients with cystic fibrosis are frequently affected with pancreatic
      insufficiency and are predisposed to the development of diabetes mellitus (DM)
      and bone demineralization. Cystic fibrosis-related diabetes mellitus is a
      clinical entity distinct from type 1 and type 2 diabetes, with important
      implications for the nutritional and pulmonary health of cystic fibrosis
      patients. This form of diabetes owes largely to insulin deficiency, but
      alterations in insulin sensitivity and hepatic glucose production have also been
      described. Therapy for cystic fibrosis-related diabetes differs substantially
      from type 2 DM, with careful attention to prandial glycemic excursions crucial to
      controlling its metabolic effects. Bone disease, including osteopenia and
      osteoporosis, also occurs with increased frequency in cystic fibrosis, owing to
      defects in intestinal absorption, chronic inflammation, lung disease, low body
      weight, and gonadal dysfunction. The pathogenesis, implications, diagnosis, and
      therapy of cystic fibrosis-related bone demineralization are discussed, with
      attention to recommended approaches to prevention of and treatment of established
      bone disease.

PMID- 19760540
TI  - Genetics of cystic fibrosis.
AB  - Cystic fibrosis (CF) is a complicated disease involving many organ systems.
      Identification of the cystic fibrosis transmembrane regulator (CFTR) genetic code
      has not only enhanced our understanding of the mechanism of CF pathology but has
      also provided explanations for phenotypic variation. Additionally, genetic
      testing has refined our ability to identify patients with CF and CF-related
      illnesses. Genetic mutations may be grouped by class (I-VI) and are directly
      related to the quantity of CFTR protein produced. This has direct implications
      regarding the severity of disease and has suggested organ-specific sensitivity to
      the presence of normally functioning CFTR. Further, it has improved understanding
      of the mechanism behind seemingly organ-specific manifestations of CF, such as
      congenital bilateral absence of the vas deferens (CBVAD).

PMID- 19760541
TI  - Atypical mycobacterial and fungal infections in cystic fibrosis.
AB  - Nontuberculous mycobacteria (NTM) and fungi are prevalent in the sputum of cystic
      fibrosis patients and are increasingly recognized to cause clinically significant
      disease. In both instances the organisms are ubiquitous within the environment
      making exposure common, although specific risk factors that contribute to active
      pulmonary infection have not been identified. A consistent and aggressive
      approach to screening for NTM and fungi within the cystic fibrosis airway is
      likely indicated, especially in the setting of clinical deterioration despite
      standard antipseudomonal therapies.

PMID- 19760542
TI  - Improving care at cystic fibrosis centers through quality improvement.
AB  - Quality improvement (QI) using a clinical microsystems approach provides cystic
      fibrosis (CF) centers the opportunity to make a significant positive impact on
      the health of their patients. The availability of center-specific outcomes data
      and the support of the Cystic Fibrosis Foundation are important advantages for
      these quality improvement efforts. This article illustrates how the clinical
      microsystems methodology can improve care delivery and outcomes by describing the
      gradual application of quality improvement principles over the past 5 years by
      the CF team at the Lewis Walker Cystic Fibrosis Center at Akron Children's
      Hospital in Akron, Ohio. Using the example of a project to improve the pulmonary
      function of the pediatric patients at our center as a framework, we describe the
      QI process from the initial team-building phase, through the assessment of care
      processes, standardization of care, and developing a culture of continuous
      improvement. We outline how enthusiastic commitment from physician leadership,
      clinical managers and central administration, the availability of coaches, and an
      appreciation of the importance of measurement, patient involvement,
      communication, and standardization are critical components for successful process
      improvement.

PMID- 19760543
TI  - Lung transplantation in patients with cystic fibrosis.
AB  - Cystic fibrosis is one of the most common indications for lung transplantation
      worldwide and certainly the most common indication for all pediatric lung
      transplants and for bilateral lung transplantation irrespective of age. Outcomes
      are outstanding when compared with other indications for lung transplantation,
      and an increasing number of centers now report mean survival of greater than 10
      years posttransplant. Hence it is important to concentrate on the broad panoply
      of potential systemic complications of cystic fibrosis and address proactively
      issues that may be associated with adverse outcomes. Optimum management of
      infectious, nutritional, diabetic, renal, bone, and gut complications is critical
      to long-term success so that recipients may realize their full potential. Timing
      of referral for consideration of active listing should allow sufficient time for
      the patient and lung transplant team to develop a productive working relationship
      based on best available evidence and mutual trust, which will culminate in a long
      term successful outcome.

PMID- 19760544
TI  - Anxiety and depression in cystic fibrosis.
AB  - Symptoms of anxiety and depression have important consequences for patients with
      chronic disease, including lower rates of adherence and increased morbidity. This
      review discusses the prevalence of anxiety and depression in patients with cystic
      fibrosis (CF) across the life span and highlights current understanding of how
      these symptoms affect adherence, health outcomes, and health-related quality of
      life (HRQOL). Anxiety and depression appear to be more common in patients with CF
      than in the general population. Recent studies also indicate that symptoms of
      anxiety occur more frequently than depression in this population. Both anxiety
      and depression have been shown to be associated with poorer disease outcomes,
      including HRQOL. Depression, specifically, leads to lower adherence to
      recommended therapies. Given the prevalence and impact of anxiety and depression
      in CF, it seems appropriate to recommend annual screening using a validated
      approach, with referral for either pharmacotherapy or cognitive behavioral
      therapy of those with apparent symptoms. A large-scale epidemiological study of
      anxiety and depression in CF is under way and should provide better prevalence
      estimates and more information on the effects of these psychological symptoms.

PMID- 19760545
TI  - Nutrition in cystic fibrosis.
AB  - Cystic fibrosis (CF) is mostly recognized for its pulmonary morbidity, but the
      earliest manifestations of the disease are related to its gastrointestinal and
      nutritional derangements. Destruction of acinar pancreatic tissue, pancreatic
      ductular obstruction, and lack of enzymatic activity lead to malabsorption
      (particularly of fats), diarrhea, and failure to thrive. A minority of CF
      patients carrying milder CF transmembrane conductance regulator (CFTR) mutations
      have preserved pancreatic secretory activity and are free from significant
      malabsorption early in life. However, these patients are at risk for losing
      pancreatic function over time. Nutritional status plays an important role in the
      progression of the pulmonary disease in CF. Further, CF patients with better
      nutritional status have a survival advantage. Several factors contribute to
      impaired nutritional status in CF (e.g., pancreatic insufficiency, chronic
      malabsorption, recurrent sinopulmonary infections, chronic inflammation,
      increased energy expenditure, suboptimal intake). Progressive lung disease
      further increases calorie requirements by increasing the work of breathing.
      Treatment programs that place an emphasis on higher caloric intake and more
      aggressive nutritional management in CF patients report better outcomes. Basic
      tenets of nutritional repletion in CF include the use of pancreatic enzyme
      replacement therapy and following a high calorie, high protein, unrestricted
      diet. At the Stanford Cystic Fibrosis Center, nutritional status is assessed on
      an ongoing basis through anthropometric parameters and annual assessment of body
      composition, bone density, glucose tolerance, and various biochemical and
      micronutrient levels. Based on the anthropometric data obtained on routine
      clinical encounters, patients are categorized as to their nutritional risk. This
      proactive approach for the early identification of nutritional risk has become a
      major theme within the network of US CF centers. Aggressive nutritional support
      with adequate pancreatic replacement management should lead to both normal growth
      and lung function preservation. In addition, nutritional status has to be
      monitored closely during routine encounters to allow for early intervention once
      derangements are noted. This will include increasing calories in the early stages
      of lung disease and being vigilant of gastrointestinal symptomatology and
      complications.

PMID- 19760546
TI  - The approach to Pseudomonas aeruginosa in cystic fibrosis.
AB  - Pseudomonas aeruginosa continues to be the most common pathogen in cystic
      fibrosis (CF) lung disease, and chronic infection with mucoid strains is
      associated with an accelerated decline in lung function. Although multiple
      factors can potentially explain the susceptibility of CF airways to this
      organism, their individual relevance is still largely unclear. Prevention of
      infection remains an important task, and hygiene measures have been successful in
      reducing cross-infection, but the universal presence of the organism creates an
      ongoing challenge, and vaccination strategies have not been highly successful to
      date. Over the last decade treatment strategies have shifted from controlling
      chronic infection to attempting to eradicate P. aeruginosa in the early stages of
      infection. Multiple strategies have been shown to be efficacious, but the optimal
      form and duration of therapy have yet to be defined. Inhaled antibiotics are a
      key component of maintenance therapy for chronic infection, and the spectrum of
      available compounds is rapidly expanding. Pulmonary exacerbations can be reduced
      with this strategy but usually require intravenous antibiotic therapy once they
      occur. Nonantibiotic approaches to address P. aeruginosa infection are currently
      being developed and may expand the therapeutic repertoire in the future.

PMID- 19760547
TI  - Burkholderia cepacia complex: impact on the cystic fibrosis lung lesion.
AB  - Burkholderia cepacia complex (Bcc) is a group of phenotypically similar
      nonfermenting, aerobic, gram-negative rods that infect 2 to 8% of patients with
      cystic fibrosis (CF). Bcc comprises several distinct species (formerly termed
      genomovars). Infection with Bcc has been associated with worse outcomes and
      survival in CF patients. Additionally, colonization with Bcc has been associated
      with heightened mortality following lung transplantation. Currently, the role of
      lung transplantation in Bcc-infected patients remains controversial.
      Antimicrobial therapy for Bcc is often ineffective because most strains are
      multidrug resistant. Combination therapy with two or three agents is typically
      administered, but optimal therapy has not been elucidated. Certain strains
      (particularly B. cenocepacia) have been associated with heightened
      transmissibility and virulence. Several genes or gene products have important
      roles in virulence, persistence of the organism(s), and transmissibility. The
      incidence of Bcc and specific species fluctuates over time and between centers.
      Bcc can be transmitted by social contact, and several major epidemic strains have
      disseminated globally. Strict infection control measures, including cohorting
      (segregation) of infected patients, dramatically curtail transmission and have
      become the standard of care, but such measures cause social isolation,
      stigmatism, and psychological impact among infected patients.

PMID- 19760548
TI  - A pipeline of therapies for cystic fibrosis.
AB  - Therapeutics development for cystic fibrosis (CF) involves a coordinated effort
      among many groups, including individuals with CF and their caregivers, clinical
      research teams, and those in academia and industry who have discovered and
      developed the therapeutic strategies. In the United States, the Cystic Fibrosis
      Foundation (CFF) has devoted over $875 million to facilitate and coordinate this
      process since 1986, resulting in the clinical development and/or assessment of
      ~50 drug candidates during that time. The more than 30 compounds currently in the
      pipeline of Foundation-funded therapeutics are used as a platform to discuss why
      and how therapeutic strategies are brought into clinical development.
      Consideration is also given to the funding, management, and infrastructure
      necessary and practical to support the progression of drug candidates and the
      availability of therapeutics for use by individuals with CF. The importance of
      the clinical trial process and relevant outcome measures to assess the efficacy
      of drug candidates is also discussed. Finally, the potential impact of the
      pipeline for individuals with CF is summarized.

PMID- 19760550
TI  - [Haematology and oncology: in the vanguard of modern medicine].

PMID- 19760551
TI  - [Positron emission tomography as a tool for early prediction of therapy outcome
      in soft tissue sarcoma].
AB  - BACKGROUND AND OBJECTIVE: We used 2-deoxy-2-[(18)F] fluoro-D-glucose (FDG)
      positron emission tomography (PET) to evaluate the FDG uptake in patients with
      soft tissue sarcoma (STS). Treatment effect was assessed with regard to
      prediction of therapy outcome. PATIENTS AND METHODS: This evaluation includes 35
      patients with high risk STS receiving chemotherapy consisting of doxorubicin and
      ifosfamide (AI-G regimen) or etoposide, ifosfamide and doxorubicin (EIA regimen).
      Patients were examined using PET prior to onset of therapy and after completion
      of the first cycle of AI-G and after two cycles of EIA chemotherapy,
      respectively. Restaging according to RECIST was performed after six cycles of AI
      G or four cycles of EIA chemotherapy and served as reference. RESULTS: Clinical
      outcome of 35 evaluable patients was as follows: two patients with no evidence of
      disease (NED), eleven with partial remission (PR), 17 with stable disease (SD),
      and five patients with progressive disease (PD). A difference regarding
      progression-free survival for patients with a decrease in SUV (responders) in
      comparison to patients with an increase or stable SUV (non-responders) could be
      demonstrated (p = 0.0943). CONCLUSION: On the basis of these data, prediction of
      chemo-sensitivity of the tumour and moreover of the therapy outcome might be
      possible.

PMID- 19760552
TI  - [Blastic plasmacytoid dendritic cell neoplasm - a rare differential diagnosis of
      neoplastic skin infiltrations associated with systemic symptoms].
AB  - HISTORY AND CLINICAL FINDINGS: A 70-year-old female patient developed a non
      pruritic, indolent rash associated with infections and peripheral blood
      abnormalities. A skin biopsy was suggestive of malignant lymphoma of the skin.
      INVESTIGATIONS: The peripheral blood count showed mild pancytopenia and 12 %
      blasts. Additional immunohistochemistry of the skin specimen as well as cytologic
      and flow cytometric examination of the bone marrow revealed an immature cell
      population expressing CD4 and CD56 which infiltrated both the dermis and, with an
      infiltration grade of about 85 %, the bone marrow. DIAGNOSIS: Blastic
      plasmacytoid dendritic cell neoplasm (formerly known as blastic NK cell
      lymphoma). TREATMENT AND COURSE: After the first course of induction chemotherapy
      with daunorubicin and cytarabin, both the rash and the hematologic findings of
      bone marrow and peripheral blood showed a complete remission. CONCLUSION: The
      blastic plasmacytoid dendritic cell neoplasm is a rare, aggressive hematopoietic
      neoplasm most likely related to acute myeloid leukemia (AML). Since cutaneous
      involvement is regularly present at diagnosis, the differential diagnosis of
      unexplained skin lesions should include this disease entity, especially if
      peripheral blood abnormalities are present. Despite the initial response to
      cytostatic therapy being mostly excellent, the prognosis is poor. Hence,
      treatment as high-risk AML seems advisable.

PMID- 19760553
TI  - [89-year-old woman with hemorrhagic diathesis].

PMID- 19760554
TI  - [Diagnostics and therapy of acute myeloid leukemia].

PMID- 19760555
TI  - [Autologous stem cell transplantation in multiple myeloma - pro].

PMID- 19760556
TI  - [Autologous stem cell transplantation in multiple myeloma - contra].

PMID- 19760557
TI  - [The molecular pathogenesis of classical Hodgkin lymphoma].
AB  - Despite the fact that classical Hodgkin lymphoma (HL) has been described more
      than 170 years ago, only over the last 15 years significant advances regarding
      its molecular pathogenesis have been achieved. The lack of a specific lineage
      profile in combination with the low number of the malignant mononuclear Hodgkin-
      and multinucleated Reed-Sternberg- (HRS-) cells in the affected lymph nodes
      prevented for a long time both the identification of its cell of origin and of
      genomic and molecular defects. The development of methods for the analysis of
      micromanipulated single cells made it possible to demonstrate a B cell origin of
      HRS cells. However, it has become clear that the normal B cell-specific gene
      expression program in HRS cells is disrupted by various molecular lesions.
      Furthermore, molecular and genomic defects of various signaling pathways could be
      identified in HRS cells, including the NF-kappaB, JAK/STAT and MAPK-AP-1
      signaling pathways, which protect HRS cells from apoptotic cell death. Despite
      significant advances in the treatment of HL, the considerable long term toxicity
      of conventional therapies requires the development of new non-genotoxic
      therapeutic strategies. Therefore, it will be a central aim to develop new
      treatment strategies based on these insights into HL pathogenesis.

PMID- 19760558
TI  - [Systemic light chain amyloidosis - molecular basis and clinical perspectives].

PMID- 19760559
TI  - [Use of multimodal treatment for early-stage follicular lymphoma].

PMID- 19760560
TI  - [Non response to proton pump inhibitors in gastroesophageal reflux disease].

PMID- 19760561
TI  - [Using intensive medicine in progressive cases?].

PMID- 19760562
TI  - [Who can still sleep normally and quietly].

PMID- 19760563
TI  - [Self harm in adolescents in Flanders].
AB  - BACKGROUND: Deliberate self harm is an important precursor to suicide. Little is
      known about the epidemiology and circumstances of self harm behaviour that cannot
      be treated with medication. AIM: To use international data in order to obtain
      insight into the prevalence, the circumstances and possible ways of presenting
      self harm in adolescents in the general population in Flanders. METHOD: With the
      frameworks of the Child and Adolescent Self Harm in Europe (case)- study 4500
      Flemish adolescents were asked to complete an anonymous self-report
      questionnaire. results 10.4% of the adolescents questioned admitted to having
      engaged in self harm on one or more occasions during their life. 7% (males 4.1%,
      females 10.1%) reported they had engaged in self harm during the past year. Self
      harm seemed to be strongly associated with a family history of self harm,
      physical ill-treatment and sexual abuse. Adolescents seldom sought help from
      adults and hardly ever from professional care workers. CONCLUSIONS: Deliberate
      self harm is more common in Flanders than in other countries participating in the
      case-study. Flanders needs to set up a school-based prevention campaign and
      should take steps to lower the barriers that currently stop adolescents from
      seeking professional help.

PMID- 19760564
TI  - [Independent psychiatrists rarely dispute an application for compulsory
      admission].
AB  - BACKGROUND: In recent years in the Netherlands there has been a marked increase
      in the number of compulsory admissions, particularly those that require court
      authorisation. Little is known about the decision-making process that precedes
      the issuing of a court authorisation for compulsory admission. AIM: To obtain
      more insight into the factors that an independent psychiatrist has to consider
      when assessing whether he or she should sign a medical certificate that will
      advise on compulsory admission. METHOD: Data on clinical and demographic patient
      characteristics were gathered for 862 commitment applications. Motives for
      rejection of the application or doubt about the necessity of commitment were
      collected. results In the case of 9% of the applications, the psychiatrist
      hesitated about the need for compulsory admission but nevertheless signed the
      necessary medical certificate. In the case of 3% of the applications, the
      psychiatrist turned down the application for compulsory admission. The
      psychiatrist found to reject or query an application less often if a patient
      presented a direct physical threat to himself or others. The principal reason for
      rejecting an application for compulsory admission was the possibility that an
      alternative type of treatment was available. CONCLUSION: In principle the
      independent psychiatrist nearly always signs a medical certificate if the
      clinician treating the patient had requested a court authorisation. Factors that
      might help to reduce the number of court authorisations are better and earlier
      use of intensive care services, improved management or the deployment of legal
      restraints to prevent danger.

PMID- 19760565
TI  - [Heritability and environment in psychiatric disorders].
AB  - BACKGROUND: In recent years quantitative genetic research has addressed all the
      major psychiatric disorders. In order to interpret the results of this type of
      research one needs to be aware of its potential and its limitations. AIM: To
      discuss the basic concepts and the main results of quantitative genetic research
      and to consider how this can help us to better understand the aetiology of
      psychiatric disorders. METHODS: Using Medline (1990-February 2006) we reviewed
      the literature on the subject of quantitative genetic and psychiatric disorders.
      In addition we studied the standard books on the subject. RESULTS: A fairly large
      number of psychiatric disorders, namely about 30 to 85%, can be inherited. In
      addition, the non-shared environment has a considerable influence on the
      phenotype. The influence of the shared environment seems to have only a limited
      influence or it is totally absent. The results of quantitative genetic research
      are specific to a particular time or environment and therefore may not be
      applicable to other populations. There may be a correlation or interaction
      between genetic factors and the environment while the phenotype is being formed.
      However, because of the analytical methods used, this is only partly visible in
      the results. CONCLUSION: Quantitative genetic research has made an impressive
      contribution to our knowledge about the heritability of psychiatric disorders. By
      definition quantitative genetic research always provides information about
      environmental influences.

PMID- 19760566
TI  - [Genetic neuroimaging].
AB  - BACKGROUND: Both genetics and neuroimaging have developed rapidly in the past few
      years. Recently the two methods have been combined in a new technique called
      genetic neuroimaging. AIM: To provide an overview of the backgrounds and the
      possibilities of genetic neuroimaging. METHOD: In this review we first discuss
      genetic and neuroimaging research methods that are currently in use and then
      discuss their synergistic combination. Finally we analyse two recent cases in
      which genetic neuroimaging was used to study an individual's vulnerability to
      affective and psychotic symptoms. results Results are very promising,
      particularly with regard to research into vulnerability to psychiatric disorders.
      It is expected that the use of genetic neuroimaging procedures will increase.
      Genetic and neuroimaging methods are often exceedingly complex, which means they
      cannot be easily accessed by the general public. CONCLUSION: Genetic neuroimaging
      is an important method to study the relation between candidate genes and
      variations in cognitive and emotional functioning and the vulnerability to
      psychiatric disorders.

PMID- 19760567
TI  - [Introducing the diagnostic inventory for depression in the Netherlands].
AB  - BACKGROUND: The Diagnostic Inventory for Depression (did) is a new self-report
      questionnaire based on the dsm-iv inclusion criteria for a major depressive
      disorder. AIM: To analyse the Dutch translation of the did and examine the
      psychometric properties of the inventory. methods We conducted a large-scale
      internet-based screening among the general population. results Reliability,
      convergent validity and factor structure were good. The did-nl may classify
      participants accurately. CONCLUSION: The results look promising and the did-nl
      can give added value to existing questionnaires. However, since the
      classification potential has not yet been sufficiently demonstrated, a clinical
      interview will still be needed.

PMID- 19760568
TI  - [Time-limits on collaboration between the emergency mental health services and
      the police: a practice-based evaluation in the City of Utrecht, the Netherlands].
AB  - National and regional agreements have been reached with regard to time-limits on
      collaboration between the emergency mental health services and the police. On the
      basis of 69 emergency cases attended by both the crisis-team and the police in
      Utrecht, we investigated whether the time-limits had been observed in that city.
      Of the cases 85% were dealt with adequately within 6 hours (in accordance with
      the national guideline and 20% within 2 hours (regional norm). The average time
      needed to reach an emergency case was 1 hour 35 minutes, but was longer when the
      emergency resulted from substance abuse. The average time required for case
      assessment was 1 hour 25 minutes and was longer in cases requiring compulsory
      detention and in cases involving manic behaviour.

PMID- 19760569
TI  - [Less need for insulin, a surprising effect of phototherapy in insulin-dependent
      diabetes mellitus].
AB  - A 40-year-old woman with insulin-dependent diabetes mellitus was treated
      successfully with phototherapy for a seasonal affective disorder. Following
      sessions of phototherapy she developed hypoglycaemias and required less insulin.
      A review of the literature showed that melatonin has an inhibiting effect on
      insulin sensitivity. The melatonin secretion, which is suppressed by
      phototherapy, may cause an immediate decrease in the plasma glucose levels. This
      decrease may well be important for patients with insulin-resistant diabetes
      mellitus and seasonal affective disorder.

PMID- 19760570
TI  - [Clozapine use and abrupt smoking cessation; a potentially life-threatening
      combination].
AB  - A 58-year-old man was in a period of 3 weeks twice admitted to a general hospital
      with symptoms of clozapine intoxication, i.e. loss of consciousness. We are of
      the opinion that the patient developed clozapine intoxication because he had been
      prescribed clozapine (300 mg/day) and at the same time had suddenly stopped
      smoking. The link is confirmed in the literature. We therefore recommend that
      clozapine-dosage be adjusted to a patient's smoking behaviour.

PMID- 19760571
TI  - [Noninvasive measurement of cardiovascular functions: blood pressure reactivity
      to stress].
AB  - Advances in medical engineering have introduced novel tools to monitor changes in
      hemodynamics in a continuous and non-invasive manner. Blood pressure or
      cardiovascular reactivity to laboratory-induced mental stresses in individuals
      with certain traits or diseases differs from that of healthy controls. Therefore,
      blood pressure reactivity to stress can be used as an index of cardiovascular
      function. It can also be used in research to elucidate linkages between
      exaggerated blood pressure response and cardiovascular disease. This paper
      introduces the stress response and its physiologic mechanisms, blood pressure
      reactivity, short-term regulation of blood pressure, and blood pressure
      reactivity assessment methods.

PMID- 19760572
TI  - [Nursing care of patients with implantable cardioverter defibrillators].
AB  - The implantable cardioverter defibrillator (ICD), developed by Drs. Michel
      Mirowski and Morton Mower in the late 1960s, has since been established as an
      efficient intervention to prevent sudden cardiac death. However, most patients
      express psychological distress after ICD implantation due to ICD induced
      lifestyle changes and concerns regarding the potential of receiving a
      defibrillating shock at any time. This article reviews literature articles on the
      treatment, indications, and psychological impact of implanted ICDs as well as on
      nursing care for ICD recipients. The goal is to promote quality of care for
      patients with implanted ICDs.

PMID- 19760573
TI  - [Biomarkers in heart failure: BNP and NT-proBNP].
AB  - Used as biomarkers of heart failure (HF), BNP and NT-proBNP may be considered as
      the 'fatal finish line' for all cardiovascular disorders. The incidence of heart
      failure has increased steadily over the past several decades. High readmission
      rates for patients with acute decompensated heart failure have led to a search
      for biomarkers able to predict future clinical outcomes that would facilitate HF
      patient monitoring and help guide therapy. Molecular biomarkers play an important
      role in heart failure. From among several promising markers, the family of
      natriuretic peptides, especially B-type natriuretic peptide (BNP) and NT-proBNP,
      have been identified as potentially valuable diagnostic and prognostic tools. Not
      unexpectedly, BNP/NT-proBNP fails to fulfill all the criteria of an ideal
      biomarker. The development of additional biomarkers will be an important step
      toward improving diagnosis and treatment of patients with chronic and acute
      decompensated heart failure.

PMID- 19760574
TI  - [Evidence-based practice of fluid restriction in patients with heart failure].
AB  - Heart failure (HF) is prevalent in the aging population. Both pharmacological and
      non-pharmacological therapies are employed in HF and have yielded significant
      improvements in survival and quality of life. Body fluid must be maintained at a
      level sufficient to ensure hemodynamic stability and adequate tissue perfusion,
      which may decrease neurohormonal activation caused by low cardiac output in
      patients with HF. However, shortness of breath and peripheral edema caused by
      fluid overload remain the most common clinical symptoms of HF, causing patient
      distress. In addition to routine pharmacologic approaches, fluid restriction is
      frequently suggested in HF management strategies. The purpose of this review of
      published studies that examined use of fluid/water restriction as an intervention
      was to determine the optimal fluid intake for HF patients in clinical practice.
      Four articles describing three clinical trials were identified via PubMed and
      CINAHL. Their findings suggest that patients with clinically stable HF receiving
      optimal pharmacological treatment may not benefit from fluid restriction.
      Patients in these studies had preserved renal function, however, and the trials
      had no long-term follow-up period. Clinicians choosing to restrict fluid intake
      for patients with HF should consider an individualized fluid prescription,
      potentially based on patient body weight, sodium intake, and likelihood of
      adherence. Further clinical trials are warranted to improve clinical practice in
      caring for patients with HF.

PMID- 19760575
TI  - [A study on the psychological state of nurse-students of a university in affected
      areas of Wenchuan earthquake].
AB  - BACKGROUND: The 8.0-magnitude earthquake that struck Wenchuan County in Sichuan
      was the most destructive earthquake to hit China since the People's Republic of
      China was founded in 1949. It caused great environmental harm and property
      damage, and brought considerable psychological stress and emotional problems to
      many in the population. PURPOSE: This study was designed to investigate the
      psychological state of nursing students studying at a university located within
      the Wenchuan earthquake zone. METHODS: Nurses were recruited using a striated
      cluster sampling approach. The study was conducted using a self-designed
      questionnaire, Self-Rating Depression Scale (SDS), Self-Rating Anxiety Scale
      (SAS), Social Support Rating Scale (SSRS) and Coping Style Questionnaire.
      RESULTS: Most (68.8%) participants lacked sufficient knowledge regarding the
      earthquake, and the social support condition of college nursing students was
      lower than the population average (p < .001). However, degree of anxiety and
      depression was higher than the population average (p < .001). SSRS scores and its
      three dimensions were positively correlated with SAS scores and negatively
      correlated with SDS scores (p < .001). Participants most often employed basic
      problem solving approaches to deal with psychological conflicts arising from
      their earthquake experience. No significant difference between nursing students
      in different class years in terms of study variables was identified. CONCLUSION:
      Nursing students in areas affected by the Wenchuan earthquake suffer from anxiety
      and depression disorders. Adequate social support represents an important
      intervention needed to maintain and enhance their mental health.

PMID- 19760576
TI  - [Exploring factors affecting meaning of life perceptions among ESRD elders].
AB  - BACKGROUND: The number of patient with end stage renal disease (ESRD) has been
      growing in Taiwan. Nearly 50% of ESRD sufferers are 65 years of age or older. The
      disease as well as issues related to patient physiology, psychology, and
      spiritual well-being are worth taking seriously. While research into this topic
      area has been conducted, most studies addressed issues in the physiological and
      psychological dimensions. Studies addressing the domain of spiritual well-being
      remain inadequate. The purpose of this study was to explore factors affecting
      meaning of life perceptions in ESRD elders. METHODS: Using a descriptive
      correlation research approach, we employed purposive sampling to collect data
      from 80 ESRD elders currently under the care of a hemodialysis center in southern
      Taiwan. Research instruments used included a demographic questionnaire and
      Meaning in Life Scale. Data were analysed using SPSS 12.0 software. RESULTS:
      Findings showed that ESRD elders had relatively low meaning in life scores
      compared to the overall ESRD population in Taiwan. Influencing factors included
      education level, socio-economic status, and level of participation in leisure
      activities. CONCLUSION: Study findings may provide health professionals a better
      understanding of meaning of life perceptions amongst elders with ESRD, and, as a
      result, help them target better spiritual care and supportive interventions.

PMID- 19760577
TI  - [Fatigue and related factors in patients with Parkinson's disease].
AB  - BACKGROUND: While fatigue ranks as one of the most common symptoms of Parkinson's
      disease (PD), few studies on PD-related fatigue have been done in Taiwan.
      PURPOSE: The purpose of this study was to explore PD fatigue and fatigue-related
      factors. METHODS: A descriptive and correlation study design was used. Using
      purposive sampling, we recruited 100 subjects from a medical center in northern
      Taiwan. Data were analyzed using Pearson product-moment correlation, independent
      t-test, chi-square test, one way ANOVA, multiple regression and logistic
      regression. RESULTS: Results showed that: (1) about 46% of participants reported
      fatigue symptoms; (2) UPDRS (Unified Parkinson's Disease Rating Scale) total
      score, Hoehen and Yahr stage (H&Y), daily L-dopa dose (mg), quality of sleep and
      depression symptoms each correlated positively with level of fatigue. The Schwab
      and England score (SES) correlated negatively with level of fatigue; (3)
      depression inclination explained 45.0% of variance in fatigue among subjects; (4)
      depression inclination was a significant fatigue predictor (OR = 5.357, 95% CI =
      2.27-12.65) among participants. CONCLUSION: Fatigue associated with PD is a
      common and under-appreciated problem. The present study confirms UPDRS total
      score, HYS, daily L-dopa dose (mg), quality of sleep, depression symptoms and SES
      to correlate positively with level of fatigue. Assessment of fatigue should be
      part of the routine evaluation procedures used with PD patients to promote
      healthcare quality.

PMID- 19760578
TI  - [Biological measures in nursing research: a discussion of accuracy and
      precision].
AB  - In addition to psychological measures, nurse researchers have been working hard
      to integrate biological measures into their research in order to gain a
      comprehensive understanding of client health status. However, the fluctuating and
      interactive nature of biological systems makes biological measurement a
      significant challenge to researchers. To obtain objective and valid biological
      measurement results, it is important to ensure levels of accuracy and precision
      that are comparable to validity and reliability concepts current in the
      psychometrics field. The purpose of this article was to describe the concept and
      issue of accuracy and precision in biological measurement. To reduce measurement
      errors, researchers must understand the potential difficulties in measuring
      living organisms and the characteristics of biomedical devices used. The ultimate
      goal is to conduct biological measurements in a highly accurate and precise
      manner. The authors conducted a systematic overview of nursing studies that
      adopted biological measurement run between 2004 and 2008. Among the 42 eligible
      articles, 50% (n = 21) described both accuracy and precision of the biological
      measurement used, whereas 31% (n = 13) did neither. Findings suggest the
      importance of adequately describing accuracy and precision of biological
      measurement in nursing studies still needs to be emphasized in order to enhance
      nursing research rigor.

PMID- 19760579
TI  - [Recognition and management of Tourette syndrome].
AB  - Tourette syndrome (TS) is a chronic tic disorder that occurs in childhood.
      Children with TS may have multiple tic incidents during a day, even many times
      per minute. Such sudden, rapid and short utterings or movements may influence
      sufferers' ability to perform daily activities and present barriers to normal
      interaction with others. Anger, depression and low self-esteem are commonly seen
      in many children with TS. Awareness of TS is not great in Taiwan, and so many
      pediatric patients fail to obtain an early diagnosis and / or are mistreated or
      punished due to disorder-related behaviors. Such results in elevated physical,
      psychological and social stresses for sufferers. In this paper, we briefly
      introduce TS symptoms, diagnosis, classification, prognosis, co-morbidity,
      related psycho-social stresses, and common treatments. In order to facilitate the
      effective management of TS, we provide suggestion for patient families and
      schools as well as recommendations on how to interact effectively with others. We
      hope this article is helpful for healthcare workers, patients, families and
      schools to improve the recognition and management of TS.

PMID- 19760580
TI  - [Standardized nursing language: the bedrock of computerized nursing records].
AB  - Taiwan is currently in the initial phase of implementing a nursing information
      system. In order to successfully achieve effective communications across
      dispersed and diverse populations, care settings, and locations, standardized
      language within the nursing profession must be established and promoted. However,
      standardized nursing language is not well known among Taiwanese nurses. This
      article introduces the definition of standardized nursing language, the
      importance of standardized nursing language to the nursing profession, and the
      relationship between nomenclatures and standardized nursing language.
      Additionally, twelve language standards recognized by the American Nurse
      Association and the ICNP (International Classification for Nursing Practice)
      developed by International Council of Nurses are briefly introduced. In Taiwan,
      although cross-mapping of ICNP terms with handwritten nursing records has been
      done, further research must be done to reach practical conclusions. The authors
      hope this article will help Taiwanese nurses learn more about standardized
      nursing language and, consequently, contribute more toward the implementation of
      the nursing information system in Taiwan.

PMID- 19760581
TI  - [Myth of neonatal umbilical cord care].
AB  - Umbilical cord care is a common practice after birth. Although most hospitals
      routinely use alcohol in the administration of cord care to newborns in Taiwan,
      the literature suggests that other different cord-care regimens may also be as or
      more effective. The purpose of this paper is to compare the effect of different
      cord-care regimens on cord separation time, colonization, omphalitis occurrence,
      and maternal satisfaction. Findings are hoped to provide nurses information
      essential to consider and select an optimal approach to umbilical cord care.

PMID- 19760582
TI  - [Application of leventhal "illness representation" in nursing practice].
AB  - The self-regulation model proposed by Leventhal and colleagues is one theoretical
      model that addresses how cognitive and emotional factors influence coping
      behaviours and outcomes. The model depicts a self- regulative system that
      integrates illness representation (cognitive and emotional), coping procedures
      used to manage threats, and criteria used by the individual to evaluate coping
      process outcomes (appraisal). This model describes a system whereby an
      individual's cognitive and emotional construction of an illness guides his/her
      coping, appraisal and ultimate health behaviour. The five components identified
      in the cognitive illness representation include identity, cause, timeline,
      consequence and control/cure. The overview and analysis discussed in this paper
      will help nurses better understand the "spirit" of illness representation and
      further apply such in clinical practice to assess correctly illness perception
      and provide more appropriate interventions to improve illness self-management.

PMID- 19760583
TI  - [Concept analysis of health literacy].
AB  - Health literacy has risen to become one of the dominant issues in Taiwan's
      healthcare system today. Level of health literacy impacts upon public health
      outcomes. Nevertheless, healthcare professionals in Taiwan remain largely
      unfamiliar with the concept and importance of health literacy. This paper employs
      concept analysis as described by Walker & Avant to introduce and analyze the
      attributes, antecedents and consequences of health literacy. Defining attributes
      of health literacy include: 1. enabling an individual to function successfully in
      a healthcare context; 2. facilitating the obtaining, comprehending, communicating
      and evaluating of health information to make appropriate health decisions and
      conduct positive health practices; and 3. achieving a good health status. The
      antecedent of health literacy is literacy. Consequences of health literacy
      include differences in health outcomes such as health knowledge, use of
      healthcare services and health status. Hopefully, through concept analysis,
      findings can help promote nursing clinical practice and related research quality.

PMID- 19760584
TI  - [Hospice care nursing experience related to a patient with terminal stage liver
      cancer].
AB  - This case report describes hospice care provided to a patient suffering from
      terminal stage liver cancer. Care was analyzed based on the Neuman System Model.
      In the nursing process, the author first established a good relationship with the
      patient and then collected information related to patient physical, mental and
      spiritual needs through discussions, observations and anamnesis. Results revealed
      that sources of pressure affecting patient functional system harmony came from
      two intrinsic factors; namely, intrapersonal and interpersonal stressors.
      Intrapersonal stressors included changes in nutritional status, aches, and
      struggles with fear of death. Interpersonal stressors addressed the guilt of
      being unable to meet the expectations of family members. Based on the Neuman
      System Model, patient pressures were analyzed at three levels of prevention in
      order to strengthen their ability to cope. The scope of intervention included (1)
      alleviate problems of aches and malnutrition resulting from abdominal dropsy in
      the terminal stage of cancer; (2) provide psychological and spiritual care in
      order to ease patient fears of death and encourage positive reflection on life;
      (3) position the family to perform a positive role to help the patient and his
      family obtain the best quality of life. The patient finally passed away in the
      company of his family in a dignified, peaceful and painless manner.

PMID- 19760585
TI  - [Applying uncertainty theory in caring for the family of a von Willebrand disease
      patient experiencing first time upper gastrointestinal bleeding].
AB  - The purpose of this report was to describe the nursing experience in helping a
      primary caregiver cope with uncertainty as his mother experienced upper
      gastrointestinal (UGI) bleeding underlying von Willebrand disease and
      Scleromyxedema in an Emergency Department between 10 and 18 July 2008. Mishel's
      Uncertainty Theory was applied to assess the caregiver's uncertainty and patient
      disease progression. Data were collected through clinical observation, chart
      review, and interviews. The caregiver's nursing problems were identified as (1)
      uncertainty caused by symptoms of the rare disease and the probability of
      recurrent bleeding in the future; (2) uncertainty caused by lack of knowledge
      about the disease; (3) uncertainty caused by lack of confidence in home caring
      issues after UGI bleeding. During the nursing period, we provided clinical
      information related to the disease and offered psychological support to the
      caregiver based on our Mishel's Uncertainty Scale assessment. Successful
      strategies utilized by our intervention helped the caregiver reduce level of
      uncertainty, increase confidence to care for his mother, and improve the quality
      of further home care.

PMID- 19760586
TI  - Lymphatic spread of mesenchymal renal tumor to metastatic parathymic lymph nodes
      in rat.
AB  - Rat mesenchymal renal tumor cells (NeDe) transplanted under the kidney capsule of
      F344 rats resulted in metastases in the parathymic lymph nodes. Tumor cells were
      isolated from these tumor-bearing lymph nodes and 106 cells were implanted under
      the kidney capsule. Tumor growth after this implantation could be traced within
      six days. India ink was implanted to prove that there is a connection between the
      lymphatic vessels of the kidney capsule and the parathymic lymph nodes. The
      distribution of the radioligand 18FDG in different organs also provided evidence
      that the parathymic lymph nodes are the primary sites of metastatic tumor growth.
      Tumor growth was followed after staining sections of biopsies of normal, tumorous
      kidneys and parathymic lymph nodes embedded in paraffin. The progression of tumor
      formation was seen as a frontline between the healthy and tumor bearing tissue.
      This demarcation line was sharp at the beginning of the invasion and at the
      peripheral regions of the tumor, while the central region infiltrated into the
      healthy kidney tissue. The initial invasion gradually turned to an infiltration
      resulting in the disruption of the renal tissue, especially at the periphery.
      Accumulation of lipids and flow of blood to the lymphatic vessels was due to the
      lack of angiogenesis, leading to an increased pressure of the interstitial fluid.
      Interstitial damage ultimately led to the appearance of blood and the growth of
      tumor cells in parathymic lymph nodes. The kidney capsule-parathymic lymph node
      complex is proposed as a suitable metastatic model for the isolated in vivo
      examination of tumor development and for the analysis of secondary tumors.

PMID- 19760587
TI  - MUC-1-/ESA+ progenitor cells in normal, benign and malignant human breast
      epithelial cells.
AB  - The existence of mammary epithelial stem/progenitor cells has been demonstrated
      in MUC-1-/ESA+ subpopulations of breast epithelial cells. However, knowledge
      about the expression and localization in benign and malignant breast lesions is
      unknown. Using a double-staining immunohistochemistry method, we investigated MUC
      1-/ESA+ cells in 10 normal breast tissues, 49 cases with fibrocystic disease, 40
      fibroadenomas, 36 invasive ductal carcinomas and the breast cancer cell lines MCF
      7 and MDA-MB-468. In normal breast tissues MUC-1-/ESA+ cells were mainly found in
      the suprabasal layer, but under the apical surface of the duct/alveolus. In the
      hyperplastic areas of fibrocystic disease, the number of this subpopulation of
      cells was higher than that in hypoplastic areas and in fibroadenomas. In invasive
      ductal carcinoma, the MMUC-1-/ESA+ cells were heterogeneously present in
      different carcinoma nests. In the MCF-7 cell line most cells were MUC-1-/ESA+,
      and in the MDA-MB-468 cell line MUC-1-/ESA+ cells and MUC-1-/ESA+ cells were
      almost equal. Our results show that the MUC-1-/ESA+ subpopulation increases in
      fibrocystic disease within the hyperplastic areas, and varies in benign and
      malignant breast tumours, indicating that breast carcinogenesis may develop from
      malignant changes of normal MUC-1-/ESA+ cells.

PMID- 19760588
TI  - Critical role of von Willebrand factor and platelet interaction in venous
      thromboembolism.
AB  - It has been generally considered that platelets are less important in venous
      thrombus formation. However, clinical studies have shown an association between
      venous thromboembolism (VTE) and von Willebrand factor (VWF). We therefore
      investigated the contribution of VWF and platelet interaction to the onset of VTE
      using tissues from autopsies and from an animal model. An immunohistochemical
      study revealed that glycoprotein (GP) IIb/IIIa, fibrin, glycophorin A
      (erythrocyte-specific protein) and VWF were consistently localized in ilio
      femoral venous thrombi and in pulmonary thromboemboli from 8 autopsied cases who
      died of VTE, and VWF was closely associated with GPIIb/IIIa and fibrin. Venous
      thrombi and pulmonary emboli contained significant amounts of GPIIb/IIIa and VWF,
      in addition to glycophorin A and fibrin, and the factors did not significantly
      differ between them. A rabbit model of VTE was developed by inserting a
      polyethylene tube into the iliac vein. The constituents of the induced thrombi
      were quite similar to those of human VTE. An antibody against VWF (AJW200), which
      inhibits interactions between the VWF A1 domain and platelet GPIb, significantly
      reduced venous thrombus formation and pulmonary thromboembolism in the model.
      These results suggest that VWF A1-platelet GPIb interaction plays a significant
      role in venous thrombus formation.

PMID- 19760589
TI  - FOXP1 status in splenic marginal zone lymphoma: a fluorescence in situ
      hybridization and immunohistochemistry approach.
AB  - Splenic marginal zone lymphoma (SMZL) is a well-recognized entity in which
      chromosomal aberrations seem to be potential markers in diagnosis, prognosis and
      disease monitoring. FOXP1 is a transcriptional regulator of B lymphopoiesis that
      is deregulated in some types of NHL. Translocation t(3;14)(p14;q32) has been
      described in marginal zone lymphomas but few series have studied FOXP1
      involvement in SMZL. We performed cytogenetic, fluorescence in situ hybridization
      (FISH) and immunohistochemical (IHC) studies in a series of 36 patients in order
      to study the status of FOXP1 in this entity. According to our results, FOXP1 is
      not rearranged in SMZL, although we were able to demonstrate gains of FOXP1 gene
      due to trisomy 3/3p by FISH. FOXP1 protein expression seemed to be not related to
      any aberration and IHC studies are not conclusive.

PMID- 19760590
TI  - Temporal and spatial distribution of TGF-beta isoforms and signaling
      intermediates in corneal regenerative wound repair.
AB  - The present study analyzed the temporal and spatial expression of TGF-beta
      isoforms and activated pSmad2 and p38MAPK during epithelial debridement wound
      repair, using chick cornea by immunohistochemistry. Normal corneas showed low
      level TGF-betas staining. Following wounding, TGF-beta1 expression was strong in
      the Bowman's layer (BL). TGF-beta3 expression was confined to basal cells in the
      regenerating and unwounded regions, and was not detected in migrating epithelial,
      stromal or endothelial cells. In addition, TGF-beta3 treatment stimulated the
      proliferation of cultured epithelial cells. Our present findings seem to suggest
      that the TGF-beta3 signal may be required for epithelial cell proliferation. TGF
      beta2 expression was strong in migrating and proliferating epithelial cells, many
      active migrating fibroblasts at the wound edge, endothelial cells and Descemet's
      membrane (DM). Although both nuclear pSmad2 and p38MAPK staining was observed in
      many basal epithelial cells, pSmad2 positive cells were co-localized with PCNA
      positive cells. Therefore, it seems likely that the pSmad2 signal may affect
      epithelial cell proliferation in healing corneas. Both pSmad2 and p38MAPK
      expression were also observed in endothelial cells. Interestingly, many active
      fibroblasts over the whole stroma in early wound healing at day 2 expressed
      nuclear pSmad2, but little if any cytoplasmic p38MAPK. Collectively,
      temporal/spatial up-regulation and distribution of the three TGF-beta isoforms,
      as well as concerted activation of both Smad2 and p38MAPK, appears to be a key
      aspect of regenerative corneal wound healing in the chick.

PMID- 19760591
TI  - Effects of photo stimulation and nonstimulation of golden hamsters (Mesocricetus
      auratus) from birth to early puberty on testes structure and function.
AB  - We tested whether puberty in golden hamsters is photoperiodically controlled.
      Hamsters were raised under 14:10 hours Light:Dark (14L) and 1:23 hours Light:Dark
      (1L) respectively, from birth to 28 days and tested for various parameters. Body
      weight, Leydig cell (LC) size and testicular testosterone secretion were greater
      and plasma thyroxin (T4), testicular androstenedione secretion and LC number were
      lower (P<0.05) in 1L than 14L hamsters. Volumes of testicular components were
      similar in the two groups. 3beta-hydroxy steroid dehydrogenase
      immunohistochemistry demonstrated LC progenitors and newly formed adult LC (ALC)
      in 14L hamsters, which were absent in 1L hamsters; they contained only fetal LC
      (FLC). Latter findings suggest the presence and absence of postnatally
      differerentiated LC in 14L and 1L hamsters, respectively. Androgen results agreed
      with these findings, because FLC primarily secrete testosterone, and
      androstenedione is a major androgen secreted by the newly formed ALC. Reduced T4
      in 1L hamsters is attributed to the inhibition of thyroid function by the
      increased duration of melatonin secretion due to non-photostimulatory conditions.
      The arrest in LC differentiation in 1L hamsters is attributed to low T4 levels.
      Although the testis size is unaltered under non-photostimulatory conditions,
      postnatal LC differentiation is inhibited in golden hamsters, and therefore, it
      is logical to suggest that their puberty is photoperiodically controlled.

PMID- 19760592
TI  - Staining patterns of keratins in the human urinary tract.
AB  - The keratins, members of the intermediate filament family, are characteristically
      expressed in epithelial cells. In the various types of epithelia, the keratin
      expression pattern is characterized by cell-type specific combinations of the
      keratin isotypes with a plain pattern in monolayered (simple) epithelia and more
      complex patterns in stratified and pseudostratified epithelia. Here we
      demonstrate that the transitional epithelium of the human urinary tract holds an
      exceptional position between the pseudostratified and stratified epithelia. We
      show that the simple epithelia keratins 7, 8, 18 and 19 are expressed throughout
      the whole epithelium as known from pseudostratified epithelia. In addition, we
      demonstrate expression of keratins 5, 14 and 17, otherwise present in basal cells
      of multilayered epithelia, and keratins 4 and 13, present in suprabasal areas of
      non cornified multilayered epithelia. Moreover, we report differences in
      expression in the various morphological parts of the urinary tract which might be
      related to their specific functions. Keratin 20, a typical component of the
      simple epithelia of the digestive tract, is present in bladder and ureter but not
      in the renal pelvis. Keratin 6, typical for stratified epithelia, is found only
      in parts of the renal pelvis. We further show that changes in keratin pattern
      occur during the development from embryonic to adult bladder urothelium. In
      contrast to adult tissue, the simple type keratins 7, 8 and 18 are not
      synthesized in basal embryonic cells. Further, keratin 20, present in cells
      facing the bladder lumen in adult urothelium, is expressed in all but the basal
      cells in embryonic bladder.

PMID- 19760593
TI  - The MHC-related protein 1 (MR1) is expressed by a subpopulation of CD38+, IgA+
      cells in the human intestinal mucosa.
AB  - MHC-related 1 (MR1) molecule is a non-classical member of the MHC class I family
      of proteins. The sequence homology between classical MHC class I molecules and
      MR1 is very high, although the MR1 gene is not polymorphic and is highly
      conserved between species. MR1 is the restriction molecule of a sub-population of
      T lymphocytes, which are CD4-,CD8- and display conserved TCR alpha chain. The
      function of these cells is currently unknown, but they are believed to have
      regulatory properties similar to those of the CD1d restricted NKT cells. The MR1
      gene is ubiquitously transcribed; however it is unknown what types of cells
      express the MR1 protein "in vivo". In the present work we analyzed the expression
      of the MR1 protein using specific antisera and monoclonal antibodies in different
      human cell lines, in primary cells and in mucosal tissues. We found some lymphoid
      cell lines that express MR1 on the cell surface but at levels much lower than the
      MR1 transfected cell lines. In addition, we observed that expression of MR1 in
      the mucosa is restricted to a subpopulation of plasma cells or plasmablasts,
      CD38+ or CD138+ and IgA+, located in the human intestinal mucosa. This suggests a
      function for MR1 in the development of IgA producing plasma cells.

PMID- 19760594
TI  - The transcription factor Fos: a Janus-type regulator in health and disease.
AB  - The immediate early gene product Fos is part of the activator protein-1 (AP-1)
      transcription factor and has been shown to participate in the molecular
      mechanisms of cell proliferation, differentiation, apoptosis, and transformation.
      The analysis of genetically modified mice and cells derived thereof has provided
      important new insights into its specific biological functions in development,
      tissue homeostasis, and cellular responses to environmental insults. Moreover,
      the deregulation of Fos could be linked with a variety of pathological
      conditions, including immunological, skeletal and neurological defects, as well
      as oncogenic transformation and tumor progression. In contrast to the mainstream
      opinion concerning the oncogenic function of Fos an increasing number of
      experimental reports also describe a tumor-suppressive function in various cancer
      types. More recently, altered Fos expression in cell culture and mouse models
      combined with global gene expression analysis unraveled novel downstream
      effectors of the Fos-regulated genetic program. Finally, selective inhibition of
      its function with a small molecule inhibitor in a preclinical mouse model of
      arthritis demonstrated that targeting Fos/AP-1 activity could be an auspicious
      new option for clinical use.

PMID- 19760595
TI  - Tight junction proteins and signal transduction pathways in hepatocytes.
AB  - Tight junctions of hepatocytes play crucial roles in the barrier to keep bile in
      bile canaliculi away from the blood circulation, which we call the blood-billiary
      barrier (Kojima et al., 2003). Tight junction proteins of hepatocytes are
      regulated by various cytokines and growth factors via distinct signal
      transduction pathways. They are also considered to participate in signal
      transduction pathways that regulate epithelial cell proliferation, gene
      expression, differentiation and morphogenesis. This review focuses on recent
      findings about the relationship between tight junction proteins and signal
      transduction pathways in hepatocytes.

PMID- 19760596
TI  - A role for monomeric C-reactive protein in regulation of angiogenesis,
      endothelial cell inflammation and thrombus formation in
      cardiovascular/cerebrovascular disease?
AB  - Native CRP (nCRP) is a pentameric oligoprotein composed of identical 23 KDa
      subunits which can be irreversibly dissociated to form free subunits or monomeric
      CRP (mCRP). mCRP has a reduced aqueous solubility and a tendency to aggregate
      into matrix-like lattices in various tissues, in particular, blood vessel walls.
      A dramatic increase in expression of mCRP occurs in angiogenic blood vessels
      derived from stroked brain regions, atherosclerotic arteries and active vessels
      from other angiogenic diseases such as Alzheimer's. Furthermore, mCRP unlike the
      native molecule is highly angiogenic to vascular endothelial cells in vitro and
      therefore might impact on the processes of vascularization and re-modelling thus
      affecting tissue survival and development. In this mini-review, we will discuss
      the differences in the biological properties between nCRP and mCRP. We will
      provide a brief historical background to the importance of nCRP as a biomarker
      for cardiovascular disease. We will explain the mechanisms of conversion of nCRP
      to its monomeric form and describe evidence for the role of mCRP in modulation of
      endothelial cell activation, promotion of inflammatory status and thrombus
      formation in cardio/cerebrovascular disease. Finally, we will provide evidence
      for the accumulation of mCRP in angiogenic microvessels from diseased tissue, and
      demonstrate its highly pro-angiogenic capabilities. The discovery of the
      existence of this tissue-associated, highly angiogenic monomeric form of CRP
      capable of cellular binding and intra-cellular signal transduction activation may
      help in our understanding of the processes responsible for modulation of
      angiogenesis and inflammation in disease.

PMID- 19760597
TI  - Hepatocyte nuclear factor-1beta(HNF-1beta) in human urogenital organs: its
      expression and role in embryogenesis and tumorigenesis.
AB  - Molecules responsible for embryogenesis are often involved in tumorigenesis.
      Recent exhaustive cDNA microarray analyses in human neoplasms expanded knowledge
      of such molecules. Hepatocyte nuclear factor-1beta (HNF-1beta) is a homeobox
      transcription factor that functions as a homodimer or heterodimer with HNF
      1alpha. In contrast to HNF-1alpha, HNF-1beta is very weakly expressed in the
      liver and is commonly expressed in the kidneys. During human embryonic stage, HNF
      1beta plays an important role in organogenesis, especially of the urogenital
      system. In the human fetus, HNF-1beta expression is common in mesonephric duct
      derivatives and metanephros (permanent kidneys). HNF-1beta germline mutations
      cause malformations of these structures. Recent microarray analyses have
      disclosed that HNF-1beta is aberrantly up-regulated in clear cell carcinoma of
      the ovary, which is a carcinoma of mullerian nature, but which was initially
      misnamed "mesonephroma". HNF-1beta is also expressed in ovarian endometriosis,
      which is a probable origin of clear cell carcinoma. On the other hand, HNF-1beta
      is down-regulated in renal neoplasms, such as chromophobe cell carcinoma. In this
      review, we first summarize HNF-1beta expression in the developing urogenital
      system of the human embryo. Then, we describe the HNF-1beta status in human
      urogenital neoplasms and discuss its role in tumorigenesis.

PMID- 19760598
TI  - Behavioural responses of the maize weevil, Sitophilus zeamais, to host (stored
      grain) and non-host plant volatiles.
AB  - BACKGROUND: Four-arm olfactometer bioassays were conducted to assess the
      behavioural responses of the adult maize weevil, Sitophilus zeamais (Motschulsky)
      (Coleoptera: Curculionidae), to harvested seeds of host plants, i.e. white maize,
      yellow maize (Zea mays L.) and winter wheat (Triticum aestivum L.) (Poaceae), and
      non-host plant materials, i.e. alligator pepper, Aframomum melegueta (Rosk) K.
      Schum (Zingiberaceae), rhizomes of ginger, Zingiber officinale (Roscoe)
      (Zingiberaceae), and West African black pepper, Piper guineense Thonn and Schum
      (Piperaceae). Additional bioassays with host plant volatiles were conducted in
      the presence of three doses of non-host plant materials. RESULTS: Both sexes of
      the weevil showed strong attraction to maize and wheat seed volatiles, but were
      significantly repelled (P < 0.001) by odours from A. melegueta, Z. officinale and
      P. guineense. Furthermore, S. zeamais avoided maize and wheat seeds presented in
      combination with the non-host plant material at 10% (w/w) and 33% (w/w) levels.
      CONCLUSIONS: A. melegueta, Z. officinale and P. guineense have the potential for
      use in the protection of stored grains by resource-poor farmers with local access
      to these plants.

PMID- 19760599
TI  - Developmental expression of prion protein and its ligands stress-inducible
      protein 1 and vitronectin.
AB  - Prion protein (PrP(C)) is the normal isoform of PrP(Sc), a protein involved in
      neurodegenerative disorders. PrP(C) participates in neuritogenesis,
      neuroprotection, and memory consolidation through its interaction with the
      secreted protein stress-inducible protein 1 (STI1) and the extracellular matrix
      protein vitronectin (Vn). Although PrP(C) mRNA expression has been documented
      during embryogenesis, its protein expression patterns have not been evaluated.
      Furthermore, little is known about either Vn or STI protein expression. In this
      study, PrP(C), STI1, and Vn protein expression was explored throughout mouse
      embryonic life. We found that the distributions of the three proteins were
      spatiotemporally related. STI1 and Vn expression became evident at E8, earlier
      than PrP(C), in the nervous system and heart. At E10, we observed, in the spinal
      cord, a gradient of expression of the three proteins, more abundant in the
      notochord and floor plate, suggesting that they can have a role in axonal growth.
      As development proceeded, the three proteins were detected in other organs,
      suggesting that they may play a role in the development of nonneural tissues as
      well. Finally, although STI1 and Vn are PrP(C) ligands, their expression was not
      altered in PrP(C)-null mice.

PMID- 19760600
TI  - Quantification of the three-dimensional morphology of coincidence detector
      neurons in the medial superior olive of gerbils during late postnatal
      development.
AB  - In the mammalian medial superior olive (MSO), neurons compute the azimuthal
      location of sound sources by temporally precise coincidence detection. It is
      assumed that the dendritic morphology of MSO neurons plays a crucial role in this
      computational process. However, few quantitative data about the morphology of
      these neuronal coincidence detectors are available, limiting theoretical
      approaches. Such a quantitative morphological description of neurons of the
      mammalian MSO would also allow a comparative analysis with its avian analog, the
      nucleus laminaris. We used single-cell electroporation, microscopic
      reconstruction, and compartmentalization to extract anatomical parameters of MSO
      neurons and quantitatively describe their morphology and development between
      postnatal day 9 and 36. We found that developmental refinement occurs until P27,
      generating morphologically compact, cylinder-like cells with axons originating
      from the soma. The complexity of higher order dendrites decreases between
      postnatal days 9 and 21. This decrease in dendritic complexity is judged from
      counting and analyzing the location of dendritic branches and determining the
      distribution of the surface area and total length of neurons. During this
      developmental period, the average length of terminal branches increases about
      twofold, indicating an elimination of predominantly small branches. The cell
      volume increases more than 1.5-fold between P9 and P27, a change that can be
      attributed to an increase in dendritic diameter during this developmental period.
      The developmental profile of the morphology of MSO neurons obtained indicates
      that maturation is reached 2 weeks after hearing onset.

PMID- 19760601
TI  - Localization of circadian clock protein BMAL1 in the photoperiodic signal
      transduction machinery in Japanese quail.
AB  - The circadian clock is a fundamental property of living organisms and is involved
      in seasonal (photoperiodic) time measurement. Among vertebrates, birds have
      multiple circadian pacemakers in the eye, the pineal gland, and the
      suprachiasmatic nucleus (SCN), and have highly sophisticated photoperiodic
      mechanisms. However, because the removal of these circadian pacemakers fails to
      abolish the photoperiodic response, the existence of another "photoperiodic
      clock" has been suggested. Recent studies have revealed that the mediobasal
      hypothalamus (MBH) and the adjacent pars tuberalis (PT) of the pituitary gland
      constitute key components of the photoperiodic signal transduction machinery. In
      the present study, we generated a polyclonal antibody against the chicken
      circadian clock protein BMAL1 to examine BMAL1 distribution in the Japanese quail
      brain by using immunohistochemistry. BMAL1-like immunoreactivity (lir) was
      confirmed in the pineal gland and the medial SCN, which are critical circadian
      pacemakers. We also observed strong immunoreactivity in the MBH, including the
      ependymal cells (ECs), the infundibular nucleus (IN), the median eminence (ME),
      and the adjacent PT. Furthermore, semiquantitative analysis suggested that BMAL1
      lir shows daily fluctuation in these regions. It is possible that circadian
      clocks in the photoperiodic signal transduction machinery such as the PT and the
      EC may be involved in the regulation of photoperiodism.

PMID- 19760602
TI  - t(19;22)(q13;q12) Translocation leading to the novel fusion gene EWSR1-ZNF444 in
      soft tissue myoepithelial carcinoma.
AB  - Myoepithelial neoplasms of soft tissue have only recently been acknowledged as a
      separate diagnostic entity. To know based on histological appearance whether
      these tumors are benign or malignant is often difficult, and their tumorigenic
      mechanisms remain poorly understood. We report a myoepithelial carcinoma with an
      aberrant near-diploid karyotype, 43 approximately
      47,XX,add(1)(p34)x2,add(3)(q27)x2,del(12)(q22),+add(18)(p11)x2,del(22)(q11),+r,
      found in cells cultured from a lung metastasis. The deletion in 22q led us to
      search by molecular cytogenetic means for possible EWSR1 rearrangements, and
      eventually a novel chimeric gene consisting of the 5'-end of EWSR1 (22q12) and
      the 3'-end of ZNF444 (19q13) was found. How the new fusion gene contributes to
      tumorigenesis is unknown, but the finding of an EWSR1 rearrangement suggests that
      this, possibly even the EWSR1-ZNF444, is a defining pathogenetic feature of at
      least a subset of these tumors.

PMID- 19760603
TI  - OCT4B expression in PBMNCs suggests the existence of an alternative OCT4
      promoter.

PMID- 19760604
TI  - Two candidate tumor suppressor genes, MEOX2 and SOSTDC1, identified in a 7p21
      homozygous deletion region in a Wilms tumor.
AB  - A SNP-based array analysis of 100 Wilms tumors (WT) from 97 patients identified
      7p alterations (hemizygous and homozygous deletions and uniparental disomy) in
      nine tumors. The homozygous deletion (HD) region of 7p21 found in one tumor
      partially overlapped with another HD region reported previously, and was narrowed
      down to a 2.1-Mb region. Based on an expression analysis of 10 genes located in
      the HD region in 3 WT lines and previous studies on tumorigenic roles of MEOX2
      and SOSTDC1, we further analyzed these two genes. Sequencing showed no mutation
      in MEOX2, but two missense mutations (L50F and Q129L) in SOSTDC1 in four tumors;
      L50F in two tumors was of germline origin. Expression levels (0, 1+ and 2+) of
      MEOX2 were lower in four tumors with 7p alterations than in 18 tumors with no 7p
      alterations (P = 0.017), and those of SOSTDC1 tended to be lower in five tumors
      with 7p alterations or SOSTDC1 mutation than in 17 tumors with no 7p alterations
      or SOSTDC1 mutation (P = 0.056). There were no significant differences in
      clinical characteristics between nine patients with 7p alterations and 88
      patients with no 7p alterations; however, there was a difference in the status of
      IGF2 (uniparental disomy, loss of imprinting, or retention of imprinting) between
      the two patient groups (P = 0.028). Losses of MEOX2 and SOSTDC1 may accelerate
      angiogenesis and augment signals in the Wnt pathway, respectively. Both genes may
      be prime candidates for 7p tumor suppressor genes, which may have a role in the
      progression of Wilms tumorigenesis.

PMID- 19760605
TI  - Characterization of B- and T-lineage acute lymphoblastic leukemia by integrated
      analysis of MicroRNA and mRNA expression profiles.
AB  - Acute lymphoblastic leukemia (ALL) is an heterogeneous disease comprising several
      subentities that differ for both immunophenotypic and molecular characteristics.
      Over the years, the biological understanding of this neoplasm has largely
      increased. Gene expression profiling has allowed to identify specific signatures
      for the different ALL subsets and permitted the identification of pathways
      deregulated by a given lesion. MicroRNAs (miRNAs) are small noncoding RNAs, which
      play a pivotal role in several cellular functions. In this study, we investigated
      miRNAs expression profiles in a series of adult ALL cases by microarray analysis.
      Unsupervised hierarchical clustering largely recapitulated ALL subgroups.
      Furthermore, we identified miR-148, miR-151, and miR-424 as discriminative of T
      lineage versus B-lineage ALL; ANOVA highlighted a set of six miRNAs-namely miR
      425-5p, miR-191, miR-146b, miR-128, miR-629, and miR-126-that can discriminate B
      lineage ALL subgroups harboring specific molecular lesions. These results were
      confirmed and extended by quantitative-PCR on a further cohort of cases. Finally,
      we used Pearson correlation analysis to combine miRNA and gene expression
      profiles. The distribution of correlation coefficients generated by comparing the
      expression of every miRNA/gene pair in our data set shows enrichment of both
      positively and negatively correlated pairs over background distributions obtained
      using randomized data. Moreover, a clear enrichment for predicted miRNA:target
      pairs is observed at negative correlation coefficient intervals. Signal-to-noise
      ratio highlighted several miRNA/gene pairs with a possible role in the disease.
      In fact, gene set enrichment analysis of genes composing the selected miRNA/gene
      pairs displays over-representation of functional categories related to cancer and
      cell-cycle regulation.

PMID- 19760606
TI  - Claspin inhibition leads to fragile site expression.
AB  - Fragile sites are hot spots for sister chromatid exchanges, translocations,
      deletions, complex rearrangements, and gene amplification. It has been
      hypothesized that rearrangements at fragile sites derive from unreplicated
      regions resulting from stalled forks that escape the ATR replication checkpoint.
      In the present study, we investigated the role of the Claspin (CLSPN) gene, which
      codes for an adaptor protein in the ATR pathway, during DNA replication stress in
      human cells. We show that the inhibition of the CLSPN gene leads to both genome
      instability and fragile site expression. Following aphidicolin treatment, we
      found a transient increase of Claspin synthesis due to its requirement to
      checkpoint activation. However, Claspin synthesis decreased after a prolonged
      aphidicolin treatment. We propose that CLSPN modulation, following an extreme
      replication block, allows rare cells to escape checkpoint mechanisms and enter
      mitosis with a defect in genome assembly. Our observations provide the basis for
      a better understanding of cell cycle checkpoints deregulation in cancer.

PMID- 19760607
TI  - LPXN, a member of the paxillin superfamily, is fused to RUNX1 in an acute myeloid
      leukemia patient with a t(11;21)(q12;q22) translocation.
AB  - RUNX1 (previously AML1) is involved in multiple recurrent chromosomal
      rearrangements in hematological malignances. Recently, we identified a novel
      fusion between RUNX1 and LPXN from an acute myeloid leukemia (AML) patient with
      t(11;21)(q12;q22). This translocation generated four RUNX1/LPXN and one
      LPXN/RUNX1 chimeric transcripts. Two representative RUNX1/LPXN fusion proteins,
      RL and RLs, were both found to localize in the nucleus and could bring the CBFB
      protein into the nucleus like the wild-type RUNX1. Both fusion proteins inhibit
      the ability of RUNX1 to transactivate the CSF1R promoter, probably through
      competition for its target sequences. Unlike RL and RLs, the LPXN/RUNX1 fusion
      protein LR was found to localize in the cytoplasm. Thus, we believe it has little
      impact on the transcriptional activity of RUNX1. We also found that fusion
      proteins RL, RLs, LR, and wild-type LPXN could confer NIH3T3 cells with malignant
      transformation characteristics such as more rapid growth, the ability to form
      colonies in soft agar, and the ability to form solid tumors in the subcutaneous
      tissue of the BALB/c nude mice. Taken together, our data indicated that the
      RUNX1/LPXN and LPXN/RUNX1 fusion proteins may play important roles in
      leukemogenesis and that deregulation of cell adhesion pathways may be
      pathogenetically important in AML. Our study also suggests that LPXN may play an
      important role in carcinogenesis.

PMID- 19760608
TI  - Aberrant DNA methylation profile and frequent methylation of KLK10 and OXGR1
      genes in hepatocellular carcinoma.
AB  - Investigating aberrant DNA methylation in the cancer genome may identify genes
      that play an important role in tumor progression. In this study, we combined
      differential methylation hybridization and a CpG microarray platform to
      characterize methylation profiles and identify novel candidate genes associated
      with hepatocellular carcinoma (HCC). The genomic DNA of 21 paired adjacent normal
      and HCC samples was used, and results were analyzed by hierarchical clustering.
      Twenty-seven hypermethylated candidates and 38 hypomethylated candidates were
      obtained. Six candidate genes from the hypermethylated group were validated by
      combined bisulfite restriction analysis; two genes, human kallikrein 10 gene
      (KLK10) and oxoglutarate (alpha-ketoglutarate) receptor 1 gene (OXGR1), were
      further analyzed by bisulfite sequencing. The DNA hypermethylation status of
      KLK10 and OXGR1 were subsequently examined in HCC cell lines and clinical samples
      using methylation-specific PCR. In 49 HCC samples, 46 (94%) showed that at least
      one of these two genes was highly methylated. Moreover, KLK10 and OXGR1 mRNA
      levels were inversely correlated (r = -0.435 and -0.497, P < 0.05) with DNA
      methylation as examined in paired adjacent normal and tumor samples. Statistical
      analyses further indicated that KLK10 hypermethylation was significantly
      associated with cirrhosis (P = 0.042) and HCV infection (P = 0.017) as well as
      inversely associated with HBV infection (P = 0.023). Furthermore, restoration of
      KLK10 and OXGR1 expression reduced the ability of anchorage-independent growth,
      and sensitized HCC cells to doxorubicin- or 5-fluorouracil-induced cytotoxicity.
      Our results suggest that the hypermethylated KLK10 and OXGR1 are frequent in HCC
      and may be useful as markers for clinical application.

PMID- 19760609
TI  - WTX inactivation is a frequent, but late event in Wilms tumors without apparent
      clinical impact.
AB  - Wilms tumor (WT) is one of the most common solid tumors in childhood. Mutations
      in WT1 and CTNNB1 are well established as causal alterations in about 10-15% of
      cases. Recently, WTX (WT gene on the X-chromosome), a gene implicated in WNT
      signaling, has been identified as a third WT gene. We determined the mutation
      status of WTX, CTNNB1, and WT1 in a large set of 429 tumors. Genomic WTX
      alterations were identified in 17% of WTs, equally distributed between males and
      females. Analysis of 104 WT samples for WTX point mutations revealed a rate of
      only 2%. An additional 11.5% of tumor samples lacked expression of WTX mRNA.
      These WTX alterations can occur in parallel to WT1 or CTNNB1 mutations. However,
      we could not find a significant correlation between WTX deletion status or
      expression level and clinical parameters suggesting that WTX mutations apparently
      have little direct impact on tumor behavior and presentation. Incomplete
      deletions of WTX in several cases suggested heterogeneity in tumors. In a small
      number of cases, we could analyze separate tumor fragments or microdissected
      regions with different histology of tumors with heterozygous point mutations.
      Despite complete allele losses at other sites in the genome, we detected varying
      degrees of WTX mutation. This suggests that WTX alteration is not an essential
      and early mutation needed to drive tumorigenesis, but rather a later event that
      may affect only a fraction of cells with unclear clinical relevance.

PMID- 19760610
TI  - Genomic alterations in primary breast cancers compared with their sentinel and
      more distal lymph node metastases: an aCGH study.
AB  - Metastatic potential of breast cancer may be associated with specific genomic
      alterations and the earliest metastases are likely to be found in the sentinel
      lymph nodes (SLN). Using array comparative genomic hybridization (aCGH), we
      compared the genomes of primary breast invasive duct carcinomas (IDCs), their
      sentinel and more distal lymph node metastases, and IDCs without nodal
      metastasis. Thirty-three samples from 22 patients with IDC were subjected to
      aCGH: 8 IDC samples from patients without lymph node metastasis, 11 IDCs
      associated with SLN metastases out of which 7 had paired samples of metastases,
      and 14 samples of lymph node metastases out of which 8 were sentinel-distal pairs
      from 4 patients. aCGH data were analyzed by correlation of genomic profiles,
      cluster analysis, segmentation, and peak identification. Quantitative real-time
      PCR was used for data validation. We observed high genomic similarity between
      primary tumors and their nodal metastases as well as between metastases to the
      sentinel and distal lymph nodes. Several recurrent alterations were detected
      preferentially in IDC associated with SLN metastases compared to IDCs without
      metastasis. Amplification within the 17q24.1-24.2(59.96-62.76 Mb) region was
      associated with presence of sentinel or distal lymph node metastases; larger
      tumor size and higher histological grade. In our samples, there were genomic
      events associated with metastatic progression, which could be detected in both
      primary tumors and LN metastases. Gain on 17q24.1-24.2 is a candidate region for
      further testing as a predictor of nodal metastasis.

PMID- 19760611
TI  - Multiple testing for bioequivalence with pharmacokinetic data in 2 x 2 crossover
      designs.
AB  - To evaluate globally the average bioequivalence of a test drug to a reference
      drug in a pharmacokinetic (PK) study under a 2 x 2 crossover design, we consider
      directly comparing the associated drug concentration-time curves. Statistical
      models for the drug concentrations are suggested when the concentrations measured
      at different time points are distributed according to a generalized gamma
      distribution and the mean concentrations over time is described by a one
      compartment PK model. A multiple test based on the supreme distance between the
      two curves over the time interval under study is then proposed for testing the
      equivalence of the two drug concentration-time curves. The results of a Monte
      Carlo study suggest that, comparative to the conventional univariate and
      bivariate tests, the proposed test is more powerful for detecting the global
      bioequivalence and superior on maintaining its level when the global
      bioequivalence is violated. The application of the proposed tests is finally
      illustrated by using the data in a PK study involving two brands of benzbromarone
      tablets for reducing the uric acid.

PMID- 19760612
TI  - The role of salvage surgery in patients with recurrent squamous cell carcinoma of
      the oropharynx.
AB  - BACKGROUND: The objective of this study was to comprehensively review overall
      survival, functional outcomes, and prognostic factors in patients who underwent
      salvage surgery for locally recurrent squamous cell carcinoma of the oropharynx
      (SCCOP) after initial radiotherapy. METHODS: The authors retrospectively reviewed
      1681 consecutive patients who completed definitive therapy for primary SCCOP and
      identified 168 patients with locally recurrent SCCOP who underwent salvage
      surgery (41 patients), reirradiation or brachytherapy (18 patients), palliative
      chemotherapy (70 patients), or supportive care (39 patients). RESULTS: Twenty-six
      of 39 patients (67%) developed a second recurrence after salvage surgery. The 3
      year overall survival rate for patients who underwent salvage surgery or received
      reirradiation, palliative chemotherapy, or supportive care were 48.7%, 31.6%,
      3.7%, and 5.1%, respectively. For patients who underwent salvage surgery, older
      age (P=.03), the absence of a disease-free interval (P<.01), and advanced
      recurrent tumor stage (P=.07) were associated with lower overall survival.
      Patients with recurrent neck disease (P=.01) and positive surgical margins
      (P=.04) had higher rates of recurrence after salvage surgery. Postoperative
      complications occurred in 19 patients (46%), and there were no perioperative
      deaths. Functionally, 71% of patients demonstrated>or=80% speech intelligibility,
      68% were able to tolerate some oral intake, and 87% who required a tracheotomy
      subsequently were decannulated. CONCLUSIONS: Age, disease-free interval,
      recurrent tumor stage, recurrent neck disease, and surgical margin status
      influenced overall survival or recurrence rate after salvage surgery for
      recurrent SCCOP. Although most patients had good functional outcomes, only a
      select group of patients with recurrent SCCOP achieved long-term survival after
      salvage surgery.

PMID- 19760614
TI  - Protective effects of melatonin in reduction of oxidative damage and
      immunosuppression induced by aflatoxin B1-contaminated diets in young chicks.
AB  - In the present study, the ability of aflatoxin B(1) (AFB(1) ) to induce
      endogenous oxidative damages and the possible ameliorating effects of dietary
      melatonin (MEL) were investigated. Newly hatched broiler chicks (n = 240) were
      fed aflatoxin-contaminated diets (0.5 or 1 mg kg(-1) diet) with or without MEL
      (40 mg kg(-1) bw) supplementation in diet for 40 days. AFB(1) resulted in a
      significant increase in lipid peroxidation (LPO) in the liver and erythrocytes
      accompanied with suppression of superoxide dismutase (SOD) and catalase (CAT)
      enzyme activities of erythrocytes. It also caused a significant reduction in
      levels of serum proteins and marked elevation in activities of serum
      transaminases. AFB(1) treatment also decreased both humoral and cell-mediated
      immune responses in growing chicks. Simultaneous administration of MEL with
      AFB(1) resulted in an obvious improvement in all the tested parameters. Long-term
      rather than short-term administration of MEL was more effective in rendering
      protection against AFB(1)-induced toxicity.

PMID- 19760615
TI  - Assessing toxicity of nanoparticles using Brachionus manjavacas (Rotifera).
AB  - Rotifers are major components of zooplankton in freshwater and coastal marine
      ecosystems throughout the world and could be useful indicator species, providing
      valuable insight into the effects of nanoparticles on microinvertebrate grazers.
      Here we report initial efforts to characterize the immediate and longer-term
      effects of nanoparticle exposure on the reproduction of the coastal marine and
      salt lake rotifer Brachionus manjavacas. We used chemically unreactive
      fluorescent nanoparticles to probe how size and concentration affects the mode of
      uptake, distribution within the rotifer body, reproductive rate, feeding
      behavior, and offspring fitness. Population growth rate (r) was depressed 50% in
      rotifer populations exposed to 0.30 MUg mL(-1) of 37-nm particles, and 89% in
      populations exposed to 1.1 MUg mL(-1). Larger particles of identical chemical
      composition, but with diameters up to 3000 nm, caused no reduction in population
      growth rate. These larger particles remain confined in the gut, implicating
      nanoparticle size as a critical factor in the ability to penetrate the gut wall
      and enter tissues. Transfer of the F1 offspring from nanoparticle exposed
      maternal females into nanoparticle-free media demonstrated that nanoparticles are
      rapidly cleared from the animals with no significant residual adverse effects.

PMID- 19760616
TI  - beta-Benzene hexachloride induces apoptosis of rat Sertoli cells through
      generation of reactive oxygen species and activation of JNKs and FasL.
AB  - beta-benzene hexachloride (beta-BHC), the major metabolite of benzene
      hexachloride (BHC), is a weak estrogen-like chemical. It is a known persistent
      organic pollutant and male reproductive toxicant. However, the mechanism by which
      beta-BHC exposure causes male reproductive toxicity remains unknown. In the
      present study, rat Sertoli cells were used to investigate the molecular mechanism
      involved in beta-BHC-induced toxicity in male reproductive system. The results
      indicated that beta-BHC exposure at over 30 MUM showed the induction of apoptotic
      cell death. beta-BHC could induce elevation in reactive oxygen species (ROS)
      generation, increase in the leakage rate of LDH and MDA level, and decrease in
      SOD activity. In addition, there was an increase in the cellular levels of
      phospho-JNKs and FasL in the beta-BHC-induced apoptosis; and a significant
      reduction of procaspase-3 and -8 was observed over 30-MUM beta-BHC treatment. The
      translocation of NF-kappaB enhanced with the increase of concentration of beta
      BHC. Furthermore, NAC administration, a scavenger of ROS, reversed beta-BHC
      induced apoptosis effects via inhibition of JNKs activation, FasL expression, and
      NF-kappaB translocation. These results lead us to speculate that ROS generation
      may play a critical role in the initiation of beta-BHC-induced apoptosis by
      activation of the JNKs, translocation of NF-kappaB, expression of FasL, and
      further activation of caspase cascade.

PMID- 19760617
TI  - Involment of p53, Bax, and Bcl-2 pathway in microcystins-induced apoptosis in rat
      testis.
AB  - It has been reported that microcystins (MCs) could accumulate in the gonads of
      mammals and MCs exposure exerts obvious toxic effects on male reproductive system
      of mammals. We have comfirmedthat MCs could accumulate and induce apoptosis in
      rat testis. The p53, Bax, and Bcl-2 protein play important roles in mitochondria
      dependent apoptotic pathway, and this study aimed to investigate whether the p53,
      Bax, and Bcl-2 pathway is involved in microcystins-induced apoptosis in rat
      testis and discussed the possible mechanisms. Our results show that MCs led to
      persistent increase of transcriptional and protein level of P53 and Bax
      expression but led to decrease of Bcl-2 expression, resulting in an increased
      ratio of Bax to Bcl-2, which might contribute to apoptotic cell death of rat
      testis following MCs treatment. The increased ratio of expression of Bax to that
      of Bcl-2 induced by MCs suggests their important role in MCs-induced apoptosis in
      rat testis tissue.

PMID- 19760618
TI  - Tributyltin causes obesity and hepatic steatosis in male mice.
AB  - Organotin compounds such as tributyltin (TBT) have been used worldwide in
      agriculture and industry as biocides, heat stabilizers, and chemical catalysts.
      However, few studies addressing the effects of TBT on growth and metabolism have
      been reported. This study was conducted to investigate the effects of TBT at low
      doses (0.5, 5, and 50 MUg/kg) on body weight gain in male mice exposed as from
      puberty and to determine the alterations in related hormones. The results showed
      that exposure to TBT for 45 days resulted in an increase in body weight gain and
      hepatic steatosis accompanied with hyperinsulinemia and hyperleptinemia.
      Reduction of hepatic adiponectin levels in a dose-dependent manner was related to
      the lipid increase in the liver. These results suggest that chronic and repeat
      exposure to low doses of TBT can result in obesity and hepatic steatosis and
      induce the occurrence of insulin and leptin resistance.

PMID- 19760620
TI  - Connective tissue involvement in two patients with features of cranioectodermal
      dysplasia.
AB  - Cranioectodermal dysplasia (CED) is an infrequently described autosomal recessive
      disorder characterized by craniofacial, ectodermal and skeletal abnormalities,
      and associated with increased risk of chronic renal failure. A degree of joint
      laxity has been noted in some CED patients, but significant skin and soft-tissue
      laxity has not previously been highlighted as part of the syndrome. We report on
      two unrelated patients with CED and significant connective tissue involvement,
      including cutis laxa, hernias, and joint laxity. We conclude with a brief
      discussion of the differential diagnosis.

PMID- 19760621
TI  - Cranioectodermal dysplasia: a probable ciliopathy.
AB  - Cranioectodermal dysplasia (CED), also known as Sensenbrenner syndrome, is a rare
      autosomal recessive genetic disorder characterized by typical craniofacial,
      skeletal and ectodermal defects, and tubulointerstitial nephritis leading to
      early end-stage renal failure. We report on a new familial case of a 9-year-old
      patient and two fetuses of 23 and 19 weeks of gestation respectively.
      Hypohidrosis was an additional ectodermal finding is the patient with CED.
      Postmortem findings in the two fetuses included acromesomelic shortening,
      craniofacial characteristics with absence of craniosynostosis, small kidneys with
      tubular and glomerular microscopic cysts, persistent ductal plate with portal
      fibrosis in the liver, small adrenals and roughly unremarkable histopathology of
      the physeal growth plate. Posterior fossa anomalies were additional findings in
      this patient and included an enlarged cisterna magna and a posterior fossa cyst.
      The above findings, in association with renal cysts, persistent ductal plate and
      portal fibrosis, introduce CED, a nonlethal genetic skeletal disorder of yet
      unknown molecular origin, as a possible member of the expanding group of
      ciliopathies.

PMID- 19760622
TI  - Maternal medication use, carriership of the ABCB1 3435C > T polymorphism and the
      risk of a child with cleft lip with or without cleft palate.
AB  - Gene-environment interactions in the periconceptional period play an increasing
      role in the pathogenesis of birth defects, including cleft lip and/or cleft
      palate (CL/P). The P-glycoprotein, encoded by the ABCB1 gene, is suggested to
      protect the developing embryo from medication and other xenobiotic exposures.
      Furthermore, maternal medication use during early pregnancy is a significant risk
      factor for CL/P offspring. Therefore, the aim of this study is to investigate the
      association between the maternal and child's functional ABCB1 3435C > T
      polymorphism, periconceptional medication exposure, and the risk of a child with
      CL/P. A case-control study was performed among 175 mothers and 98 of their
      children with CL/P and 83 control mothers and their 65 children. Information on
      medication and folic acid use was collected. Mothers carrying the 3435TT genotype
      and using medication showed a 6.2-fold (95% CI = 1.6-24.2) increased risk of
      having a child with CL/P compared to mothers carrying the 3435CC genotype and not
      using medication. Periconceptional folic acid use reduced this risk by
      approximately 30% (OR = 3.9, 95% CI = 0.9-18.0). Mothers carrying the 3435TT
      genotype, using medication and not taking folic acid showed the highest risk
      estimate (OR = 19.2, 95% CI = 1.0-369.2). These data suggest that mothers who
      carry the ABCB1 3435C > T polymorphism are at significantly increased risk for
      having offspring with CL/P, especially mothers using medication in the
      periconceptional period.

PMID- 19760623
TI  - Microarray based analysis of 3p25-p26 deletions (3p- syndrome).
AB  - Distal deletion of chromosome 3p25-pter (3p- syndrome) produces a distinct
      clinical syndrome characterized by low birth weight, mental retardation,
      telecanthus, ptosis, and micrognathia. Congenital heart disease (CHD), typically
      atrioventricular septal defect (AVSD) occurs in about a third of patients.
      Previously we reported on an association between the presence of CHD and the
      proximal extent of the deletion such that a CHD susceptibility gene was mapped
      between D3S1263 and D3S3594. In addition, we and others have suggested several
      candidate genes for the psychomotor retardation usually seen with constitutional
      3p25 deletions. In order to further investigate genotype-phenotype correlations
      in 3p- syndrome we analyzed 14 patients with cytogenetically detectable deletions
      of 3p25 (including one patient with a normal phenotype) using Affymetrix 250K SNP
      microarrays. Deletion size varied from approximately 6 to 12 Mb. Assuming
      complete penetrance, a candidate critical region for a CHD susceptibility gene
      was refined to approximately 200 kb and a candidate critical region for mental
      retardation was mapped to an approximately 1 Mb interval containing SRGAP3 but
      other 3p neurodevelopmental genes including CHL1, CNTN4, LRRN1, and ITPR1 mapped
      outside the candidate critical interval. We suggest that current evidence
      suggests that SRGAP3 is the major determinant of mental retardation in distal 3p
      deletions.

PMID- 19760624
TI  - Subjective life satisfaction and mental disorders among older adults in UAE in
      general population.
AB  - BACKGROUND: Life satisfaction is widely considered to be a central aspect of
      human welfare. Many have identified happiness with it, and some maintain that
      well-being consists largely or wholly in being satisfied with one's life.
      Empirical research on well-being relies heavily on life satisfaction studies.
      AIMS: The aim of this study was to examine the relationships of psychiatric
      disorders and physical disorders on life satisfaction among Arab older adults in
      general population. METHODS: Face-to-face interviews with Geriatric Mental State
      Interview (GMS-A3) were conducted with a nationwide sample of 2000 household in
      2001. Total samples of 610 elders (above 60 years) were interviewed. RESULTS:
      There were 347 males (56.9%) and 263 females (43.1%). The mean age was 68.6 years
      (SD = 8.3). The commonest diagnoses were depression (20.2%), anxiety (5.6%),
      hypochondriasis (4.4%), and organic brain syndrome with or without dementia
      (3.6%). The findings suggest that having depressive disorder was significantly
      associated with less life satisfaction in the whole sample of older adults'
      people. In addition, anxiety, hypochondriacal disorders, and organic brain
      syndrome were significantly associated with low life satisfaction. Meanwhile,
      other psychiatric disorders e.g., phobia, Obsessive Compulsive disorder (OCD),
      schizophrenia were not significantly associated with life satisfaction. No
      significant relationship was found with any physical disorders alone. The data
      further reveal that low level of life satisfaction was especially significant in
      the age group above 85 years and people who live alone or only with wife/husband.
      CONCLUSIONS: The strong influence of psychiatric disorders e.g., depression,
      anxiety, organic brain syndrome, and hypochondriasis rather than physical
      disorders suggests that a lack of meaning and worries are more detrimental to
      life satisfaction than physical frailty. The findings underscore the need to
      develop interventions that help older people deal more effectively with
      psychiatric disorders and its comorbidities. Moreover, the results suggest that
      providing family support, by not allowing older adults to live alone, may be
      especially helpful for older adults.

PMID- 19760625
TI  - A case series investigating acceptance and commitment therapy as a treatment for
      previously treated, unremitted patients with anorexia nervosa.
AB  - The aim of the present study was to evaluate the effectiveness of Acceptance and
      Commitment Therapy (ACT) for treatment of anorexia nervosa (AN) using a case
      series methodology among participants with a history of prior treatment for AN.
      Three participants enrolled; all completed the study. All participants had a
      history of 1-20 years of intensive eating disorder treatment prior to enrollment.
      Participants were seen for 17-19 twice-weekly sessions of manualized ACT.
      Symptoms were assessed at baseline, post-treatment and 1-year follow-up. All
      participants experienced clinically significant improvement on at least some
      measures; no participants worsened or lost weight even at 1-year follow-up.
      Simulation modelling analysis (SMA) revealed for some participants an increase in
      weight gain and a decrease in eating disorder symptoms during the treatment phase
      as compared to a baseline assessment phase. These data, although preliminary,
      suggest that ACT could be a promising treatment for subthreshold or clinical
      cases of AN, even with chronic participants or those with medical complications.

PMID- 19760626
TI  - Ets-1 and hypoxia inducible factor-1alpha inhibition by angiotensin II type-1
      receptor blockade in hormone-refractory prostate cancer.
AB  - BACKGROUND: Accumulating evidences have suggested that the renin-angiotensin
      system (RAS) participates in the regulation of tumor angiogenesis. We previously
      demonstrated that hormone-refractory prostate cancer (HRPC) showed significantly
      higher angiotensin II (Ang II) type-1 receptor (AT1R) expression, and that the
      AT1R blocker (ARB) exerted protective effects by inhibiting angiogenesis.
      However, the downstream transcriptional factors induced by Ang II in prostate
      cancer cells have not been fully elucidated yet. METHODS: Three human prostate
      cancer cell lines: LNCap, C4-2 and C4-2AT6 were used and analyzed. C4-2AT6 cells
      were established by culture in androgen-ablated conditioned medium for 6 months.
      RESULTS: C4-2AT6 cells showed significantly higher AT1R expression, accompanied
      by higher HIF-1alpha and Ets-1 expression in the nucleus. In C4-2AT6 cells, VEGF
      production was significantly higher than in C4-2 cells and LNCaP cells. These
      results suggested that HRPC exhibited aggressive angiogenic properties,
      accompanied by up-regulated HIF-1alpha and Ets-1. Ang II stimulated VEGF
      production in C4-2 cells and C4-2AT6 cells but not in LNCaP cells. ARB
      significantly inhibited VEGF production. Western blot analysis demonstrated that
      AngII induced nuclear expression of HIF-1alpha and Ets-1 in C4-2 and C4-2AT6
      cells, but not in LNCaP cells. ARB significantly inhibited HIF-1alpha and Ets-1
      induction in C4-2 and C4-2AT6 cells. CONCLUSIONS: This study suggests that AT1R
      blockade may have a significant impact on HRPC through the inhibition of HIF
      1alpha and Ets-1 and the resulting suppression of angiogenesis. Our results
      provide the molecular basis of the clinical benefit of ARB as an angiogenic
      inhibitor in HRPC.

PMID- 19760627
TI  - Differential expression of PCA3 and its overlapping PRUNE2 transcript in prostate
      cancer.
AB  - BACKGROUND: PCA3 is one of the most prostate cancer (PrCa)-specific markers
      described so far. Recently, a new genomic structure of PCA3 as well as new
      flanking and overlapping gene transcripts has been identified. Furthermore, a co
      regulation of PCA3 and its overlapping gene PRUNE2(BMCC1) has been suggested. Our
      aim was to assess the diagnostic performance of a new PCA3 isoform (PCA3-TS4) and
      to study the interactions between PCA3 and BMCC1 in PrCa. METHODS: We used SYBR
      Green quantitative (q)PCR with specific primers to compare PCA3 and BMCC1
      expression of normal versus tumor tissue of human prostate. PCA3-TS4 plasmid was
      created to calculate the absolute amounts of PCA3 transcripts. The androgen
      regulation of PCA3 and BMCC1 expression was studied in LNCaP and 22Rv1 cells
      stimulated with 5alpha-dihydrotestosterone. RESULTS: We have not found any
      relevant diagnostic advantage of the PCA3-TS4 isoform over the "classical" PCA3
      isoform in our group of PrCa patients. Additionally, PCA3-TS4 appears to be only
      a minor PCA3 transcript. We were also unable to confirm the hypothesis that BMCC1
      isoforms are androgen-induced in vitro. CONCLUSIONS: Despite the presence of the
      recently identified marginal PCA3 transcripts in human PrCa, the previously
      described major PCA3 isoform still constitutes the best target for diagnostic
      purposes. PCA3 and BMCC1 are overlapping genes in reverse orientation that do not
      appear to be co-regulated.

PMID- 19760628
TI  - p53 is dispensable for the induction of apoptosis after inhibition of protein
      kinase CK2.
AB  - BACKGROUND: Protein kinase CK2 is a ubiquitously expressed heterotetramer
      consisting of two catalytic alpha/alpha' and two regulatory beta subunits.
      Expression of CK2 is highly elevated in tumor cells where it protects cells from
      apoptosis. A variety of different compounds were tested as inhibitors of protein
      kinase CK2 in order to find new therapy strategies. To analyze the role of p53 in
      the response to CK2 inhibition we used one of the most specific CK2 inhibitors
      available, TBB, in different prostate cancer cell lines. METHODS: We treated
      prostate cancer cells with the CK2 inhibitor TBB and determined its effect on CK2
      activity by an in vitro phosphorylation assay and its effect on viability by an
      MTT assay. Furthermore, we analyzed changes in the expression of p53 and PARP
      cleavage by Western Blot analysis. RESULTS: Inhibition of CK2 by TBB led to a
      decrease in cell viability and apoptosis in two cell lines which express wild
      type p53 whereas two other cell lines expressing mutant or no p53 failed to show
      signs of apoptosis. Moreover, cell lines expressing wild-type p53 showed an
      increase of the amount of p53 and of its transactivation efficiency. However,
      down-regulation of p53 by RNAi showed that p53 is not necessary for the induction
      of apoptosis. CONCLUSIONS: Wild-type p53 is not necessary for the induction of
      apoptosis by TBB in prostate cancer cells.

PMID- 19760629
TI  - Bone metabolic disorder in patients with prostate cancer receiving androgen
      deprivation therapy (ADT): impact of ADT on the growth hormone/insulin-like
      growth factor-1/parathyroid hormone axis.
AB  - BACKGROUND: Although androgen deprivation therapy (ADT) has been associated with
      bone loss in patients with prostate cancer, its mechanism remains unclear. The
      growth hormone (GH)/insulin-like growth factor-1 (IGF-1)/parathyroid hormone
      (PTH) axis plays a critical role in bone synthesis, but its activity during ADT
      is also unknown. METHODS: Seventy-one patients with localized prostate cancer,
      who received ADT, were prospectively studied based on their bone mineral density
      (BMD) and blood and urine samples at the baseline and after ADT for 6 months.
      RESULTS: The IGF-1 level was correlated with BMD before ADT (rs = 0.325, P =
      0.007), but such a relationship disappeared after ADT (P = 0.565). Following ADT,
      the serum IGF-1 level increased compared with that at the baseline (22 +/- 6
      nmol/L vs. 19 +/- 5 nmol/L, respectively, P < 0.001). The serum PTH level was
      reduced after ADT (41 +/- 33 ng/L) compared with the baseline (55 +/- 44 ng/L) (P
      < 0.001), but no change was observed in the serum GH level (P = 0.691). Bone
      resorption markers such as blood N-telopeptide (NTx), urinary NTx, calcium, and
      inorganic phosphorus levels increased after ADT (P < 0.001 in all). The ratio of
      the IGF-1 level after ADT/before ADT was associated with the ratio of the value
      after ADT/before ADT of alkaline phosphatase (rs = 0.266, P = 0.025) and calcium
      (rs = 0.242, P = 0.042). CONCLUSION: Despite the unaffected GH and upregulated
      bone resorption, the serum IGF-1 level was elevated by ADT. The IGF-1 level was
      correlated with BMD before ADT, but the relationship was disrupted after ADT. IGF
      1 or its receptor in the bone may be functionally inactivated during ADT.

PMID- 19760630
TI  - Opioid use affects antioxidant activity and purine metabolism: preliminary
      results.
AB  - OBJECTIVE: More must be learned about metabolic and biochemical alterations that
      contribute to the development and expression of drug dependence. Experimental
      opioid administration influences mechanisms and indices of oxidative stress, such
      as antioxidant compounds and purine metabolism. We examined perturbations of
      neurotransmitter-related pathways in opioid dependence (OD). METHODS: In this
      preliminary study, we used a targeted metabolomics platform to explore whether
      biochemical changes were associated with OD by comparing OD individuals (n = 14)
      and non-drug users (n = 10). RESULTS: OD patients undergoing short-term methadone
      detoxification showed altered oxidation-reduction activity, as confirmed by
      higher plasma levels of alpha- and gamma-tocopherol and increased GSH/GSSG ratio.
      OD individuals had also altered purine metabolism, showing increased
      concentration of guanine and xanthosine, with decreased guanosine, hypoxanthine
      and hypoxanthine/xanthine and xanthine/xanthosine ratios. Other drug use in
      addition to opioids was associated with partly different biochemical changes.
      CONCLUSIONS: This is a preliminary investigation using metabolomics and showing
      multiple peripheral alterations of metabolic pathways in OD. Further studies
      should explore the metabolic profile of conditions of opioid abuse, withdrawal
      and long-term abstinence in relation to agonist and antagonist treatment and
      investigate biochemical signatures of opioid substances and medications.

PMID- 19760631
TI  - SRD5A2 V89L polymorphism and prostate cancer risk: a meta-analysis.
AB  - BACKGROUND: Increasing studies investigating the association between steroid 5
      alpha reductase type II gene polymorphism at codon 89 (SRD5A2 V89L) and
      susceptibility to prostate cancer (PCa) confer inconsistent results. To precisely
      estimate the relationship with more statistical power, a meta-analysis was
      performed. METHODS: A comprehensive search was conducted to identify all case
      control studies investigating such an association. Odds ratio (OR) and its 95%
      confidence interval (CI) were used to evaluate the size effect. RESULTS: Twenty
      five eligible reports were identified including 8,615 cases/9,089 controls in 33
      comparisons. In overall analysis, no significant associations were found in all
      genetic models. Subgroup analyses by ethnicity revealed that small excess PCa
      risks were observed in dominant model (OR, 1.11; 95% CI, 1.03-1.19 for (LL + VL)
      vs. VV; P < 0.01; P(heterogeneity) = 0.49) and L allele frequency comparison (OR,
      1.09; 1.03-1.15 for L allele frequency; P < 0.01; P(heterogeneity) = 0.07) in
      Europeans. Meanwhile, SRD5A2 V89L polymorphism was significantly associated with
      an increased PCa risk in men aged < or =65 under the co-dominant (OR, 1.70; 95%
      CI, 1.09-2.66 for LL vs. VV; P = 0.02; P(heterogeneity) = 0.31) and recessive
      (OR, 1.75; 95% CI, 1.14-2.68 for LL vs. (VV + VL); P = 0.01; P(heterogeneity) =
      0.12) models. However, no significant associations were found in Asians and
      Africans. CONCLUSIONS: Our study suggests SRD5A2 V89L polymorphism could play a
      low-penetrant role in PCa risk among Europeans and individuals younger than 65
      years. Additional well-designed studies are warranted to validate these findings.

PMID- 19760632
TI  - From pathogenesis to prevention of castration resistant prostate cancer.
AB  - BACKGROUND: Significant progress in understanding the molecular basis of
      castration resistant prostate cancer (CRPCa) has been achieved in recent years.
      Despite this progress, CRPCa still remains a lethal disease. Early detection and
      prevention of CRPCa may provide a new strategy to improve survival of patients
      diagnosed with PCa at risk to fail standard androgen deprivation therapy (ADT).
      METHODS: Herein, we review pathogenetic mechanisms implicated in PCa progression
      toward castration resistant disease that are detectable in hormone naive PCa to
      define relevant therapeutic targets for prevention. RESULTS: Upregulation of
      androgen receptor (AR) expression has been recognized a major determinant for the
      development of CRPCa. This hypersensitive pathway is further boosted by the
      increase of intratumoral androgen synthesis. AR mutants bind promiscuous
      steroids, and may convert AR antagonists to agonists. Various non-hormonal growth
      factor receptors transactivate the AR, even in absence of androgens (outlaw
      pathway). Finally, PCa cells can bypass the AR through various mechanisms,
      including BCL-2, COX-2, neuroendocrine differentiation. Most of these
      pathogenetic factors involved in the development of CRPCa are detectable in
      hormone naive PCa tissue even at the time of initial diagnosis, and could be
      targeted by drugs currently available. CONCLUSIONS: CRPCa is the end-stage of a
      multifactorial and heterogeneous disease process. Pathogenetic factors
      responsible for the development of the CRPCa phenotype are detectable in the
      patient's PCa tissue long before the clinical onset of the disease. This approach
      provides opportunity for early detection and prevention by targeting pathways
      relevant for the individual disease process.

PMID- 19760633
TI  - Design, synthesis and biological activities of new strobilurin derivatives
      containing substituted pyrazoles.
AB  - BACKGROUND: Strobilurins are one of the most important classes of agricultural
      fungicides. To discover new strobilurin analogues with high activity, a series of
      new strobilurin derivatives containing substituted pyrazoles in the side chain
      were synthesised and bioassayed. RESULTS: The compounds were identified by (1)H
      NMR, IR, MS and elemental analysis. Preliminary bioassays indicated that some
      title compounds exhibited excellent fungicidal activities against
      Pseudoperonospora cubensis (Burk. & Curt.) Rostovsev and Erysiphe graminis DC f.
      sp. tritici Marchal, protecting cucumber and wheat at 6.25 and 1.56 mg L(-1)
      respectively, and showed a moderately high acaricidal activity against
      Tetranychus cinnabarinus (Boisd.) at 20 mg L(-1). The relationship between
      structure and biological activity is discussed in terms of effects of the
      substituent of the pyrazole ring. CONCLUSION: The present work demonstrates that
      strobilurin analogues with substituted phenylpyrazolylmethoxymethyl side chains
      can be used as possible lead compounds for further developing novel fungicides
      and acaricides.

PMID- 19760634
TI  - Cytotoxicity and biological effects of functional nanomaterials delivered to
      various cell lines.
AB  - Functional nanomaterials that included gold, silver nanoparticles and single wall
      carbon nanotubes were delivered to two cell lines (MLO-Y4 osteocytic cells and
      HeLa cervical cancer cells) in various concentrations. The cells were found to
      uptake the nanomaterials in a relatively short time, a process that significantly
      affected the shape and the size of the cells. The percentage of cellular death,
      due to the delivery of these nanomaterials, was found to be the highest for
      carbon nanotubes and increased gradually with the concentration of these
      nanostructures. Moreover, when the nanomaterials were delivered to the cells
      combined with commonly used chemotherapeutic agents such as etoposide or
      dexamethasone, the number of the cells that died increased significantly (100
      300%) as compared with the case when only the nanomaterials or the
      chemotherapeutic agents were delivered. The experimental results were confirmed
      by Caspase 3 studies, indicating a strong interaction between the nanomaterials
      used in this study and the protein structure of the cells, which allowed a more
      effective action of the apoptotic agents. These findings could be the foundation
      of a new class of cancer therapies that are composed of both chemotherapeutic
      agents and nanomaterials.

PMID- 19760635
TI  - Spatial cluster detection for repeatedly measured outcomes while accounting for
      residential history.
AB  - Spatial cluster detection has become an important methodology in quantifying the
      effect of hazardous exposures. Previous methods have focused on cross-sectional
      outcomes that are binary or continuous. There are virtually no spatial cluster
      detection methods proposed for longitudinal outcomes. This paper proposes a new
      spatial cluster detection method for repeated outcomes using cumulative
      geographic residuals. A major advantage of this method is its ability to readily
      incorporate information on study participants relocation, which most cluster
      detection statistics cannot. Application of these methods will be illustrated by
      the Home Allergens and Asthma prospective cohort study analyzing the relationship
      between environmental exposures and repeated measured outcome, occurrence of
      wheeze in the last 6 months, while taking into account mobile locations.

PMID- 19760636
TI  - No association between variant DNA repair genes and prostate cancer risk among
      men of African descent.
AB  - BACKGROUND: Recent reports hypothesize that multiple variant DNA repair gene
      interactions influence cancer susceptibility. However, studies identifying high
      risk cancer-related genes use single gene approaches that lack the statistical
      rigor to model higher order interactions. METHODS: To address this issue, we
      systematically evaluated individual and joint modifying effects of commonly
      studied polymorphic base and nucleotide excision repair genes relative to
      prostate cancer (PCA) risk using conventional logistic regression models and
      multifactor dimensionality reduction (MDR). We hypothesized that inheriting two
      or more compromised DNA repair loci may increase PCA risk due to altered gene
      product function. Six genetic alterations were evaluated using germ-line DNA
      samples from 208 PCA cases and 665 disease-free controls via TaqMan polymerase
      chain reaction. RESULTS: With the exception of XPD 312, no association existed
      between individual DNA repair single-nucleotide polymorphisms (SNPs) and PCA.
      Individuals with the XPD 312 Asn/Asn genotype had an 8.6-fold increase in risk
      (OR = 8.59; 95% CI = 1.81-40.66). We did not observe any significant single gene
      or gene-gene interactions based on MDR modeling. CONCLUSIONS: Our findings
      emphasize the importance of utilizing a combination of traditional and advanced
      statistical tools to identify and validate single gene and multilocus
      interactions in relation to cancer susceptibility.

PMID- 19760637
TI  - Impact of experimental diabetes and insulin replacement on epididymal secretory
      products and sperm maturation in albino rats.
AB  - The present study is aimed to explore the impact of experimental diabetes and
      insulin replacement on epididymal secretory products, sperm count, motility, and
      fertilizing ability in albino rats. Prepubertal and adult male Wistar strain rats
      were made diabetic with a single intraperitoneal injection of streptozotocin
      (STZ), at 120 and 65 mg/kg body weight for prepubertal and adult rats,
      respectively. After 3 days of STZ administration, insulin was given to a group of
      diabetic rats at a dose of 3 U/100 g body weight, subcutaneously and killed after
      20 days of treatment. STZ-diabetes significantly reduced the epididymal tissue
      concentrations of testosterone, androgen-binding protein, sialic acid,
      glycerylphosphoryl choline, and carnitine, suggesting its adverse effects on the
      secretory activity and concentrating capacity of epididymal epithelium. Impaired
      cauda epididymidal sperm motility and fertility (in vivo) of STZ-diabetic rats
      imply the defective sperm maturation. Insulin replacement prevented these changes
      either partially or completely. From the above findings, it is evident that STZ
      diabetes has an adverse effect on sperm maturation, which may be due to the
      decrease in the bioavailability of testosterone and epididymal secretory
      products.

PMID- 19760638
TI  - Radical prostatectomy: influence on serum and urinary androgen levels.
AB  - BACKGROUND: The role of the prostate as an active endocrine organ and the
      hormonal changes after radical prostatectomy (RP) has not been well studied. The
      objective of this study was to investigate the serum and urine hormonal changes
      after RP. METHODS: Fifty-five healthy men with localized prostate cancer were
      enrolled in this cross-sectional study at a single academic center. We measured
      serum levels of testosterone, dihydrotestosterone (DHT), sex hormone binding
      globulin (SHBG), luteinizing hormone (LH), and follicle stimulating hormone (FSH)
      in all 55 patients preoperatively and in 53 patients 90 days postoperatively.
      Free testosterone was calculated in all patients. Inhibin B levels was analyzed
      in 44 patients pre- and postoperatively. Steroid urine profile including
      testosterone, DHT, 5alpha-androstane-3alpha,17beta-diol (3alphaAdiol), and
      androsterone (ADT) was also determined preoperatively and 90 days postoperatively
      in 18 patients. RESULTS: There were 53% increase in serum LH (P < 0.0001), 21%
      increase in serum FSH (P < 0.0001), and 13% decrease in DHT levels (P < 0.03).
      There were no significant changes in any other serum hormone investigated.
      Urinary levels of DHT glucuronides (DHT-G) decreased by 67% (P < 0.0003) while
      Androsterone-G and 3alphaAdiol-G increased by 37% (P = 0.019) and 44% (P =
      0.023), respectively. There were no alterations in the urinary levels of the
      other steroids investigated. Inhibin B levels correlated inversely with both FSH
      (r = -0.67, P < 0.0001) and LH (r = -0.51, P = 0.0004). CONCLUSION: RP leads to
      significant increases in serum gonadotropins and significant DHT decrease in both
      serum and urine. These hormonal changes are independent of inhibin B.

PMID- 19760639
TI  - Sculpturing nanowires with ion beams.

PMID- 19760640
TI  - Neutrophil apoptosis: a target for enhancing the resolution of inflammation.
AB  - Neutrophils are essential for host defense and their programmed cell death and
      removal are critical for the optimal expression as well as for efficient
      resolution of inflammation. Delayed neutrophil apoptosis or impaired clearance of
      apoptotic neutrophils by macrophages contributes to the progression of chronic
      inflammation. Under most conditions, neutrophils are exposed to multiple factors
      and their fate would ultimately depend on the balance between pro-survival and
      pro-apoptotic signals. Life or death decisions are tightly controlled by a
      complex network of intracellular signaling pathways. Accumulating data indicate
      that receptors, such as the formyl peptide receptor 2/lipoxin receptor or beta(2)
      integrins can generate contrasting cues in neutrophils in a ligand-specific
      manner and suggest a hierarchy among these signals. In this article, we review
      recent advances on how pro-apoptosis and pro-survival signals interact to
      determine the fate of neutrophils and the inflammatory response, and highlight
      novel pharmacological strategies that could be used to enhance the resolution of
      inflammation by redirecting neutrophils to apoptosis.

PMID- 19760641
TI  - Cancer stem cells: cell culture, markers, and targets for new therapies.
AB  - A cancer stem cell (CSC) is defined as an undifferentiated cell with the ability
      to self-renew, differentiate to multiple lineages and initiate tumors that mimic
      the parent tumor. In this review, we focus on glioblastomas, describing recent
      progress and problems in characterizing these cells. There have been advances in
      CSC culture, but tumor cell heterogeneity has made purification of CSCs
      difficult. Indeed, it may be that CSCs significantly vary from tumor to tumor. We
      also discuss the proposal that CSCs are resistant to radiotherapy and
      chemotherapy and play a major role in repopulating tumors following treatment. To
      overcome their resistance to conventional therapies, we may be able to use our
      extensive knowledge of the signaling pathways essential for stem cells during
      development. These pathways have potential as targets for new glioblastoma
      therapies. Hence, although there is an ongoing debate on the nature of CSCs, the
      theory continues to suggest new ideas for both the lab and the clinic.

PMID- 19760642
TI  - Atmospheric pressure thermospray ionization using a heated microchip nebulizer.
AB  - When a standard atmospheric pressure chemical ionization (APCI) or atmospheric
      pressure photoionization (APPI) ion source is used without applying the corona
      discharge or photoirradiation, atmospheric pressure thermospray ionization
      (APTSI) of various compounds can be achieved. Although largely ignored, this
      phenomenon has recently gained interest as an alternative ionization technique.
      In this study, this technique is performed for the first time on a miniaturized
      scale using a microchip nebulizer. Sample ionization with the presented microchip
      APTSI (microAPTSI) is achieved by applying only heat and gas flow to a nebulizer
      chip, without any other methods to promote gas-phase ionization. To evaluate the
      performance of the described microAPTSI setup, ionization efficiency for a set of
      test compounds was monitored as the microchip positioning, temperature, nebulizer
      gas flow rate, sample solution composition, and solvent flow rate were varied.
      The microAPTSI mass spectra of the test compounds were also compared to those
      obtained with ESI and APCI. The microAPTSI produces ESI-like spectra with low
      background noise, favoring the formation of protonated or deprotonated molecules
      of compounds that are ionizable in solution. Multiple charging of peptides
      without in-source fragmentation was also observed. Unlike ESI, however, the
      microAPTSI source can tolerate the presence of mobile phase additives like
      trifluoroacetic acid (TFA) without significant ion suppression. The microAPTSI
      source can be used with standard mass spectrometer ion source hardware, being a
      unique alternative to the present interfacing techniques.

PMID- 19760643
TI  - Adaptation of a proton transfer reaction mass spectrometer instrument to employ
      NO+ as reagent ion for the detection of 1,3-butadiene in the ambient atmosphere.
AB  - A proton transfer reaction mass spectrometer (PTR-MS) instrument was adapted to
      employ NO+ as a chemical reagent ion without any hardware changes by switching
      the reagent ion source gas from water vapor to dry air. Ionization of dry air
      within the hollow cathode ion source generates a very intense source of NO+ with
      only a minor impurity of NO2+. The intensities of the primary NO+ reagent ion and
      the unwanted impurity NO2+ are controllable and dependent on the operational
      conditions of the hollow cathode ion source. Ion source tuning parameters are
      described, which maintain an intense source of NO+ while keeping the impurity
      NO2+ signal to less than 2% of the total reagent ion intensity. This method is
      applied to the detection of 1,3-butadiene. NO+ reacts efficiently with 1,3
      butadiene via a charge exchange reaction to produce only the molecular ion, which
      is detected at m/z 54. Detection sensitivities of the order of 45 pptv for a 1-s
      measurement of 1,3-butadiene are demonstrated. We present the first real-time on
      line sub parts per billion measurement of 1,3-butadiene in the ambient
      atmosphere. The only likely interference is from 1,2-butadiene. Concurrent
      measurements of benzene are provided and suggest that the vehicular emissions are
      the predominant source of 1,3-butadiene in a suburban Boston area monitoring
      location.

PMID- 19760644
TI  - Keeping an eye on retinoblastoma control of human embryonic stem cells.
AB  - Human embryonic stem cells (hESCs) hold great promise in regenerative medicine.
      However, before the full potential of these cells is achieved, major basic
      biological questions need to be addressed. In particular, there are still gaps in
      our knowledge of the molecular mechanisms underlying the derivation of hESCs from
      blastocysts, the regulation of the undifferentiated, pluripotent state, and the
      control of differentiation into specific lineages. Furthermore, we still do not
      fully understand the tumorigenic potential of hESCs, limiting their use in
      regenerative medicine. The RB pathway is a key signaling module that controls
      cellular proliferation, cell survival, chromatin structure, and cellular
      differentiation in mammalian cells. Members of the RB pathway are important
      regulators of hESC biology and manipulation of the activity of this pathway may
      provide novel means to control the fate of hESCs. Here we review what is known
      about the expression and function of members of the RB pathway in hESCs and
      discuss areas of interest in this field.

PMID- 19760645
TI  - Characterization of S-thiolation on secreted proteins from E. coli by mass
      spectrometry.
AB  - S-thiolation is a reversible post-translational modification in which thiol
      metabolites of low molecular masses are linked to protein sulfhydryl groups
      through disulfide bonds. This modification is commonly observed in recombinant
      proteins secreted from E. coli cells. Since it can alter protein functions and
      introduce molecular heterogeneity, S-thiolation is undesirable for recombinant
      protein production. To date, few published studies have characterized thiol
      modifiers or investigated the mechanism of S-thiolation in recombinant proteins.
      In this work, reversed-phase liquid chromatography and mass spectrometry were
      used to characterize four of the most abundant thiol modifiers on recombinant
      proteins secreted from E. coli BL21 (DE3) strain. These thiol modifiers have been
      identified as glutathione, 4-phosphopantetheine, gluconoylated glutathione, and
      dephosphorylated coenzyme A. S-thiolation by these thiol modifiers increases
      protein mass by 305, 356, 483, and 685 Da, respectively. These specific mass
      increases can be used as markers for identifying S-thiolation in recombinant
      proteins.

PMID- 19760646
TI  - Mass spectrometric analysis of the glycosphingolipid-derived glycans from
      miniature pig endothelial cells and islets: identification of NeuGc epitope in
      pig islets.
AB  - Glycosphingolipid (GSL) is a major component of the plasma membrane in eukaryotic
      cells that is involved directly in a variety of immunological events via cell-to
      cell or cell-to-protein interactions. In this study, qualitative and quantitative
      analyses of GSL-derived glycans on endothelial cells and islets from a miniature
      pig were performed and their glycosylation patterns were compared. A total of 60
      and 47 sialylated and neutral GSL-derived glycans from the endothelial cells and
      islets, respectively, were characterized by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and
      collision-induced fragmentation using positive-ion electrospray ionization (ESI)
      ion-trap tandem mass spectrometry (MS/MS). In accordance with previous
      immunohistochemistry studies, the alpha-Gal-terminated GSL was not detected but
      NeuGc-terminated GSLs were newly detected from miniature pig islets. In addition,
      the neutral GSL-derived glycans were relatively quantified by derivatization with
      carboxymethyl trimethylammonium hydrazide (so called Girard's T reagent) and
      MALDI-TOF MS. The structural information of the GSL-derived glycans from pig
      endothelial cells and islets suggests that special attention should be paid to
      all types of glycoconjugates expressed on pig tissues or cells for successful
      clinical xenotransplantation.

PMID- 19760647
TI  - Selective imaging of positively charged polar and nonpolar lipids by optimizing
      matrix solution composition.
AB  - Previous studies have shown that matrix-assisted laser desorption/ionization
      imaging mass spectrometry (MALDI-IMS) is useful for studying the distribution of
      various small metabolites, particularly lipids. However, in this technique,
      selective ionization of the target molecules is imperative, particularly when
      analyzing small molecules. Since the sample clean-up procedures available for the
      MALDI-IMS of small metabolites are limited, the tissue sample will contain
      numerous molecular species other than the target molecules. These molecules will
      compete for ionization resulting in severe ion suppression. Hence, it is
      necessary to develop and optimize a sample preparation protocol for the target
      molecules. In this study, through model experiments using reference compounds, we
      optimized the composition of the matrix solution used for positively charged
      lipids in terms of the concentration of the organic solvent and presence/absence
      of alkali metal salts. We demonstrated that a high concentration of organic
      solvent in the matrix solution favors the preferential detection of lipids over
      peptides. The presence of alkali metal salts in the matrix solution was favorable
      for the detection of polar lipids, while a salt-free matrix solution was suitable
      for the detection of nonpolar lipids. Furthermore, potassium salts added to the
      matrix solution caused merging of various lipid adducts (adducts with proton,
      sodium, and potassium) into one single potassiated species. Using the optimized
      protocols, we selectively analyzed phosphatidylcholine (PC) and triacylglycerol
      (TG) with different fatty acid compositions in a rat kidney section.

PMID- 19760648
TI  - A novel DNA repair disorder with thrombocytopenia, nephrosis and features
      overlapping Cockayne syndrome.
AB  - We report on four siblings with Cockayne-like syndrome with thrombocytopenia and
      nephrotic syndrome. The parents were healthy and consanguineous, consistent with
      an autosomal recessive mode of disease inheritance. UV irradiation of fibroblasts
      revealed an intermediate sensitivity between normal and standard Cockayne
      syndrome (CS) control cells. A genome-wide linkage scan conducted using
      Affymetrix 10K arrays provided exclusion of the known CS genes in the family, and
      evidence that the disease gene maps to 1p33-p31.1. Thrombocytopenia has not
      previously been linked with CS, but two patients with CS in association with
      nephrotic syndrome have previously been documented and the phenotypes are
      compared with the patients described here. We suggest that this Cockayne-like
      phenotype with thrombocytopenia and nephrotic syndrome may be a novel DNA repair
      disorder, and propose that further investigation of other affected families may
      help identify the causative genetic defect.

PMID- 19760649
TI  - A genome-wide screen for copy number alterations in Aicardi syndrome.
AB  - Aicardi syndrome is a severe neurodevelopmental disorder that affects females or
      rarely males with a 47,XXY karyotype. Therefore, it is thought to be caused by
      heterozygous defects in an essential X-linked gene or by defects in an autosomal
      gene with sex-limited expression. Because all reported cases are sporadic with
      one exception, traditional linkage analysis to identify the mutant gene is not
      possible, and the de novo mutation rate must be high. As an alternative approach
      to localize the mutant gene, we screened the DNA of 38 girls with Aicardi
      syndrome by high-resolution, genome-wide array comparative genomic hybridization
      for copy number gains and losses. We found 110 copy number variants (CNVs), 97 of
      which are known, presumably polymorphic, CNVs; 8 have been seen before in
      unrelated studies in unaffected individuals. Four previously unseen CNVs on
      autosomes were each inherited from a healthy parent. One subject with Aicardi
      syndrome had a de novo loss of X-linked copy number in a region without known
      genes. Detailed analysis of this and flanking regions did not reveal CNVs or
      mutations in annotated genes in other affected subjects. We conclude that, in
      this study population of 38 subjects, Aicardi syndrome is not caused by CNVs
      detectable with the high-resolution array platform that was used.

PMID- 19760650
TI  - Linking the FMR1 alleles with small CGG expansions with neurodevelopmental
      disorders: preliminary data suggest an involvement of epigenetic mechanisms.

PMID- 19760651
TI  - Genomic duplication of PTPN11 is an uncommon cause of Noonan syndrome.
AB  - Noonan syndrome (NS) is a genetically heterogeneous disorder caused most commonly
      by activating mutations in PTPN11. We report a patient with hypotonia,
      developmental delay and clinical features suggestive of NS. High-resolution
      chromosome analysis was normal, and sequence analyses of PTPN11, SOS1, KRAS,
      BRAF, RAF1, MEK, and MEK2 were also normal. Array CGH revealed a single copy gain
      of 9 BAC clones at 12q24.11q24.21 (8.98 Mb in size), which encompassed the PTPN11
      locus at 12q24.13 and was confirmed by FISH analysis. Shchelochkov et al.
      [Shchelochkov et al. (2008); Am J Med Genet Part A 146A:1042-1048] reported a
      similar case and speculated that such duplications might account for 15-30% of NS
      cases with no detectable mutation in NS genes. We screened more than 250 NS cases
      without mutation in known NS disease-causing genes by quantitative PCR, and none
      of these studies produced results in the duplicated range. We also explored the
      possibility that de novo changes affecting the untranslated region (UTR) of the
      PTPN11 transcript might represent an alternative event involved in SHP2 enhanced
      expression. DHPLC analysis and direct sequencing of the entire 3' UTR in 36 NS
      patients without mutation in known genes did not show any disease-associated
      variant. These findings indicate that duplications of PTPN11 represent an
      uncommon cause of NS, and functionally relevant variations within the 3'UTR of
      the gene do not appear to play a major role in NS. However, recurrent
      observations of NS in individuals with duplications involving the PTPN11 locus
      suggest that increased dosage of SHP2 may have dysregulating effects on
      intracellular signaling.

PMID- 19760652
TI  - Case report supporting that the Barber-Say and ablepharon macrostomia syndromes
      could represent one disorder.
AB  - We report on a 7-year-old girl with unequivocal features of Barber-Say syndrome
      (BSS): generalized hypertrichosis especially at the back, dry lax skin,
      macrostomia, thin lips, cup-shaped ears, bulbous nose, hypoplastic nipples, and
      abnormal external genitalia. She also demonstrated conductive hearing impairment
      and microblepharon. BSS has been reported with ectropion (not present in our
      patient), but ablepharon and microblepharon (i.e., absent or hypoplastic eyelids)
      have always been considered as hallmarks of ablepharon macrostomia syndrome
      (AMS). This is the first report of microblepharon in BSS. Other authors have
      discussed that BSS and AMS could possibly represent one syndrome, and our report
      supports this hypothesis.

PMID- 19760653
TI  - Vitamin A deficiency in an infant with PAGOD syndrome.
AB  - PAGOD syndrome is a rare condition characterized by multiple congenital anomalies
      including pulmonary artery and lung hypoplasia, agonadism, diaphragmatic
      abnormalities, cardiac defects, omphalocele, and various genital anomalies. The
      etiology of this condition is unknown but the spectrum of birth defects is
      similar to the developmental anomalies observed in vitamin A deficiency animal
      models. We describe an infant with PAGOD syndrome phenotype. The patient had a
      normal male karyotype and no copy number changes were seen on chromosome genomic
      hybridization (CGH) microarray. Endocrine evaluation was consistent with primary
      hypogonadism. The testes and Mullerian structures were absent by imaging studies,
      raising the possibility of arrest of early gonadogenesis. The plasma free vitamin
      A was low, consistent with moderate to severe vitamin A deficiency; the maternal
      plasma vitamin A level was normal. During pregnancy maternal vitamin A is taken
      up by retinol binding protein 4 (RBP4) which is expressed in the embryonic
      visceral endoderm from pregastrulational stages. This transport is mediated via
      the specific membrane receptor for RBP, stimulated by retinoic acid 6 (STRA6).
      STRA6 is widely expressed in human organ systems including the placenta during
      embryonic development. Mutations in the STRA6 gene result in Matthew-Wood
      syndrome, which demonstrates significant phenotypic overlap with PAGOD syndrome.
      Sequencing of STRA6 coding regions in our patient, revealed no mutations. We
      present a case of PAGOD syndrome with a review of the literature, posing the
      hypothesis that a vitamin A metabolic defect, other than transport mediated by
      STRA6 receptor, might have an etiological role in the development of this
      multiple congenital anomalies syndrome.

PMID- 19760654
TI  - Myopathy and polyneuropathy in an adolescent with the kyphoscoliotic type of
      Ehlers-Danlos syndrome.

PMID- 19760655
TI  - Inherited 14q duplication and 21q deletion: a rare adjacent-2 segregation in
      multiple family members.
AB  - We present a family with multiple carriers of a subtle balanced translocation
      t(14;21)(q21.2;q21.2) and three patients with a resultant adjacent-2
      malsegregation containing a +der(14)t(14;21)(q21.2;q21.2),-21 in their chromosome
      complement. The initial study was performed when a 2-month-old female was
      referred to genetics clinic for evaluation of developmental delay, growth
      retardation, and failure to thrive. Physical findings included prominent eyes,
      micrognathia, prominent and simple external ears, camptodactyly, contractures of
      the wrists, ankles, and hips, hypoplasia of the corpus callosum, prominent atria
      and occipital horns, cerebellopontine hypoplasia; and small atrial septal defect.
      High resolution chromosomes showed an extra band on the proximal 21q and
      fluorescence in situ hybridization (FISH) demonstrated only one signal for the
      centromere of 21. Karyotypes of the parents and grandparents revealed that the
      mother and maternal grandfather were carriers of a balanced translocation, and
      the propositus contained an unbalanced chromosome complement with partial
      duplication of proximal 14q and partial deletion of proximal 21q. Investigations
      performed on an institutionalized maternal aunt revealed identical karyotypic
      abnormalities as in the propositus. More recently, array comparative genomic
      hybridization (aCGH) on a subsequent child with multiple congenital anomalies
      further out in the extended family allowed for more accurate identification of
      the breakpoints. Our investigation includes analysis on a total of 11 family
      members spanning three generations. Among those investigated, there were no
      living members with other possible consequential unbalanced translocations or
      with adjacent-2 segregation resulting in -14,+der(21). Chromosome rearrangements
      require FISH and aCGH studies for accurate identification and elucidation of the
      abnormality and breakpoints.

PMID- 19760656
TI  - Descriptive epidemiology of nonsyndromic omphalocele in Texas, 1999-2004.
AB  - Omphalocele is a congenital malformation that involves protrusion of abdominal
      contents into the umbilicus. Though omphalocele may present as a manifestation of
      several chromosomal and Mendelian syndromes, the etiology for nonsyndromic
      omphalocele is unknown. The present study sought to estimate the birth prevalence
      of nonsyndromic omphalocele in offspring of women residing in Texas from 1999 to
      2004, and to describe prevalence as a function of parental and infant demographic
      characteristics. Data on 325 cases with nonsyndromic omphalocele and 2,208,758
      live births delivered during 1999-2004 were obtained from the Texas Birth Defects
      Registry. These data were used to estimate omphalocele birth prevalence and
      obtain both crude and adjusted prevalence ratios for the association of
      nonsyndromic omphalocele with parental and infant demographic characteristics.
      Nonsyndromic omphaloceles were significantly more common among the offspring of
      women without previous live births (adjusted prevalence ratio: 1.80, 95% CI: 1.41
      2.30), compared to the offspring of women with previous live births. The
      prevalence of nonsyndromic omphalocele was also increased among women aged 25-29
      (adjusted prevalence ratio: 1.68, 95% CI: 1.12-2.50) and women aged 40 and older
      (adjusted prevalence ratio: 4.83, 95% CI: 2.63-8.86) compared to the offspring of
      women age <20, and in infants of multiple gestation pregnancies compared to
      singleton infants (adjusted prevalence ratio: 2.03, 95% CI: 1.22-3.37). In
      addition, among Hispanic women, the prevalence of nonsyndromic omphalocele was
      higher in the offspring of those born in the U.S. as compared to those born
      elsewhere (adjusted prevalence ratio: 1.50, 95% CI: 1.12-2.00). These findings
      augment the existing omphalocele literature.

PMID- 19760657
TI  - Fitzsimmons syndrome: spastic paraplegia, brachydactyly and cognitive impairment.
AB  - Fitzsimmons syndrome is an infrequently described entity comprising slowly
      progressive spastic paraplegia, brachydactyly, and cone-shaped epiphyses,
      dysarthria, and low-normal intelligence. Five patients with this syndrome have
      been reported. The cause remains unknown. Here we describe a 16-year-old boy with
      Fitzsimmons syndrome. He was noted to toe-walk at age 18 months and spasticity
      progressed slowly into a spastic gait with contractures. He has mild dysarthria
      and hypernasal speech. Brachydactyly is notable but cannot be classified into one
      of the recognized types. A cone-shaped epiphysis was apparent on the only
      available childhood radiograph. He has moderate cognitive handicap and pervasive
      developmental delay. A detailed comparison of this patient with the earlier
      described cases is presented to further delineate the condition and increase
      awareness of this syndrome.

PMID- 19760658
TI  - Selective projection patterns from subtypes of retinal ganglion cells to tectum
      and pretectum: distribution and relation to behavior.
AB  - An important issue to understand is how visual information can influence the
      motor system and affect behavior. Using the lamprey (Petromyzon marinus) as an
      experimental model we examined the morphological subtypes of retinal ganglion
      cells and their projection pattern to the tectum, which controls eye, head, and
      body movements, and to the pretectum, which mediates both visual escape responses
      and the dorsal light response. We identified six distinct morphological types of
      retinal ganglion cell. Four of these distribute their dendrites in the inner
      plexiform layer (image forming layer) and project in a retinotopic manner to all
      areas of the tectum. The posterior part of the retina has the highest density of
      ganglion cells and projects to the rostral part of the tectum, in which the
      visual field in front of the lamprey will be represented. From this area both
      orienting and evasive behaviors can be elicited. In contrast, pretectum receives
      input from two ganglion cells types that send their dendrites only to the outer
      plexiform layer or the outer limiting membrane and therefore may directly contact
      photoreceptors, and transmit information without additional delay to pretectum,
      which may be particularly important for visual escape responses. One of these two
      types, the bipolar ganglion cell, is only found in a small patch of retina just
      ventral of the optic nerve. Due to its distribution, morphology, and projections
      we suggest that this cell may control the dorsal light response.

PMID- 19760659
TI  - Ecdysteroids from Cyanotis longifolia Benth. (Commelinaceae).
AB  - Cyanotis longifolia Benth. (Commelinaceae) contains ecdysteroids, which are
      highly concentrated in the roots and flowers, whereas leaves contain only very
      low amounts and stems intermediate amounts. 20-Hydroxyecdysone is the major
      component found in all tissues, but roots also contain large amounts of 20
      hydroxyecdysone 3-acetate and ajugasterone C. A preparative experiment has shown
      that roots contain a complex ecdysteroid mixture, and the analysis of minor
      components has allowed the isolation of several already known ecdysteroids
      (polypodine B, 2-deoxy-20,26-dihydroxyecdysone, isovitexirone, poststerone)
      together with five new (ajugasterone C 3-acetate, 5beta-hydroxy-poststerone,
      poststerone 2-acetate, 14(15)-dehydro-poststerone 2-acetate, 24-epi-atrotosterone
      A [=24-methyl-ajugasterone C]) ecdysteroids that have been fully characterized. A
      preliminary investigation of 55 species belonging to 15 different genera of the
      Commelinaceae has shown that several of them contain significant concentrations
      of ecdysteroids, among which some previously uninvestigated ones appear to be
      very promising sources of ecdysteroids.

PMID- 19760661
TI  - Role of transmembrane domain 10 for the function of organic anion transporting
      polypeptide 1B1.
AB  - The liver-specific organic anion transporting polypeptides OATP1B1 and OATP1B3
      are highly homologous and share numerous substrates. However, at low
      concentrations OATP1B1 shows substrate selectivity for estrone-3-sulfate. In this
      study, we investigated the molecular mechanism for this substrate selectivity of
      OATP1B1 by constructing OATP1B1/1B3 chimeric transporters and by site-directed
      mutagenesis. Functional studies of chimeras showed that transmembrane domain 10
      is critical for the function of OATP1B1. We further identified four amino acid
      residues, namely L545, F546, L550, and S554 in TM10, whose simultaneous mutation
      caused almost complete loss of OATP1B1-mediated estrone-3-sulfate transport.
      Comparison of the kinetics of estrone-3-sulfate transport confirmed a biphasic
      pattern for OATP1B1, but showed a monophasic pattern for the quadruple mutant
      L545S/F546L/L550T/S554T. This mutant also showed reduced transport for other
      OATP1B1 substrates such as bromosulfophthalein and [D
      penicillamine(2,5)]enkephalin. Helical wheel analysis and molecular modeling
      suggest that L545 is facing the substrate translocation pathway, whereas F546,
      L550, and S554 are located inside the protein. These results indicate that L545
      might contribute to OATP1B1 function by interacting with substrates, whereas
      F546, L550, and S554 seem important for protein structure. In conclusion, our
      results show that TM10 is critical for the function of OATP1B1.

PMID- 19760662
TI  - The oligomerization of CynR in Escherichia coli.
AB  - Deletion analysis and alanine-scanning based on a homology-based interaction
      model were used to identify determinants of oligomerization in the
      transcriptional regulator CynR, a member of the LysR-type transcriptional
      regulator (LTTR) family. Deletion analysis confirmed that the putative regulatory
      domain of CynR was essential for driving the oligomerization of lambda repressor
      CynR fusion proteins. The interaction surface of a different LTTR and OxyR was
      mapped onto a multiple sequence alignment of the LTTR family. This mapping
      identified putative contacts in the CynR regulatory domain dimer interface, which
      were targeted for alanine-scanning mutagenesis. Oligomerization was assayed by
      the ability of mutant lambda repressor-CynR fusions to assemble in E. coli
      revealing interesting similarities and differences between OxyR and CynR.

PMID- 19760660
TI  - Cellular and molecular actions of Methylene Blue in the nervous system.
AB  - Methylene Blue (MB), following its introduction to biology in the 19th century by
      Ehrlich, has found uses in various areas of medicine and biology. At present, MB
      is the first line of treatment in methemoglobinemias, is used frequently in the
      treatment of ifosfamide-induced encephalopathy, and is routinely employed as a
      diagnostic tool in surgical procedures. Furthermore, recent studies suggest that
      MB has beneficial effects in Alzheimer's disease and memory improvement. Although
      the modulation of the cGMP pathway is considered the most significant effect of
      MB, mediating its pharmacological actions, recent studies indicate that it has
      multiple cellular and molecular targets. In the majority of cases, biological
      effects and clinical applications of MB are dictated by its unique
      physicochemical properties including its planar structure, redox chemistry, ionic
      charges, and light spectrum characteristics. In this review article, these
      physicochemical features and the actions of MB on multiple cellular and molecular
      targets are discussed with regard to their relevance to the nervous system.

PMID- 19760663
TI  - One-plasmid tunable coexpression for mycobacterial protein-protein interaction
      studies.
AB  - A single plasmid that allows controlled coexpression has been developed for use
      in mycobacteria. The tetracycline inducible promoter, PtetO, was used to provide
      tetracycline-dependent induction of one gene, while the Psmyc, Pimyc, or Phsp
      promoters were used to provide three different levels of constitutive expression
      of a second gene. The functions of these four individual promoters were
      established using green fluorescent protein (GFP) and a newly identified red
      fluorescence inducible protein from Geobacillus sterothermophilus strain G1.13
      (RFIP) as reporters. The tandem use of GFP and RFIP as reporter genes allowed
      optimization of the tunable coexpression in Mycobacterium smegmatis; either time
      at a fixed inducer concentration or changes in inducer concentration could be
      used to control the protein:protein ratio. This single vector system was used to
      coexpress the two-protein Mycobacterium tuberculosis stearoyl-CoA Delta(9)
      desaturase complex (integral membrane desaturase Rv3229c and NADPH oxidoreductase
      Rv3230c) in M. smegmatis. The catalytic activity was found to increase in a
      manner corresponding to increasing the level of Rv3230c relative to a fixed level
      of Rv3229c. This system, which can yield finely tuned coexpression of the fatty
      acid desaturase complex in mycobacteria, may be useful for study of other
      multicomponent complexes. Furthermore, the tunable coexpression strategy used
      herein should also be applicable in other species with minor modifications.

PMID- 19760664
TI  - Trp fluorescence reveals an activation-dependent cation-pi interaction in the
      Switch II region of Galphai proteins.
AB  - Crystal structures of Galpha(i) (and closely related family member Galpha(t))
      reveal much of what we currently know about G protein structure, including
      changes which occur in Switch regions. Galpha(t) exhibits a low rate of basal
      (uncatalyzed) nucleotide exchange and an ordered Switch II region in the GDP
      bound state, unlike Galpha(i), which exhibits higher basal exchange and a
      disordered Switch II region in Galpha(i)GDP structures. Using purified Galpha(i)
      and Galpha(t), we examined the intrinsic tryptophan fluorescence of these
      proteins, which reports conformational changes associated with activation and
      deactivation of Galpha proteins. In addition to the expected enhancement in
      tryptophan fluorescence intensity, activation of GalphaGDP proteins was
      accompanied by a modest but notable red shift in tryptophan emission maxima. We
      identified a cation-pi interaction between tryptophan and arginine residues in
      the Switch II of Galpha(i) family proteins that mediates the observed red shift
      in emission maxima. Furthermore, amino-terminal myristoylation of Galpha(i)
      resulted in a less polar environment for tryptophan residues in the GTPase
      domain, consistent with an interaction between the myristoylated amino terminus
      and the GTPase domain of Galpha proteins. These results reveal unique insights
      into conformational changes which occur upon activation and deactivation of G
      proteins in solution.

PMID- 19760665
TI  - Crystal structures of a therapeutic single chain antibody in complex with two
      drugs of abuse-Methamphetamine and 3,4-methylenedioxymethamphetamine.
AB  - Methamphetamine (METH) is a major drug threat in the United States and worldwide.
      Monoclonal antibody (mAb) therapy for treating METH abuse is showing exciting
      promise and the understanding of how mAb structure relates to function will be
      essential for future development of these important therapies. We have determined
      crystal structures of a high affinity anti-(+)-METH therapeutic single chain
      antibody fragment (scFv6H4, K(D)= 10 nM) derived from one of our candidate mAb in
      complex with METH and the (+) stereoisomer of another abused drug, 3,4
      methylenedioxymethamphetamine (MDMA), known by the street name "ecstasy." The
      crystal structures revealed that scFv6H4 binds to METH and MDMA in a deep pocket
      that almost completely encases the drugs mostly through aromatic interactions. In
      addition, the cationic nitrogen of METH and MDMA forms a salt bridge with the
      carboxylate group of a glutamic acid residue and a hydrogen bond with a histidine
      side chain. Interestingly, there are two water molecules in the binding pocket
      and one of them is positioned for a C--H...O interaction with the aromatic ring
      of METH. These first crystal structures of a high affinity therapeutic antibody
      fragment against METH and MDMA (resolution = 1.9 A, and 2.4 A, respectively)
      provide a structural basis for designing the next generation of higher affinity
      antibodies and also for carrying out rational humanization.

PMID- 19760666
TI  - Progress toward heterologous expression of active G-protein-coupled receptors in
      Saccharomyces cerevisiae: Linking cellular stress response with translocation and
      trafficking.
AB  - High-level expression of mammalian G-protein-coupled receptors (GPCRs) is a
      necessary step toward biophysical characterization and high-resolution structure
      determination. Even though many heterologous expression systems have been used to
      express mammalian GPCRs at high levels, many receptors are improperly trafficked
      or are inactive in these systems. En route to engineering a robust microbial host
      for GPCR expression, we have investigated the expression of 12 GPCRs in the yeast
      Saccharomyces cerevisiae, where all receptors are expressed at the mg/L scale.
      However, only the human adenosine A(2)a (hA(2)aR) receptor is active for ligand
      binding and located primarily at the plasma membrane, whereas other tested GPCRs
      are mainly retained within the cell. Selective receptors associate with BiP, an
      ER-resident chaperone, and activated the unfolded protein response (UPR) pathway,
      which suggests that a pool of receptors may be folded incorrectly. Leader
      sequence cleavage of the expressed receptors was complete for the hA(2)aR, as
      expected, and partially cleaved for hA(2)bR, hCCR5R, and hD(2L)R. Ligand-binding
      assays conducted on the adenosine family (hA(1)R, hA(2)aR, hA(2)bR, and hA(3)R)
      of receptors show that hA(2)aR and hA(2)bR, the only adenosine receptors that
      demonstrate leader sequence processing, display activity. Taken together, these
      studies point to translocation as a critical limiting step in the production of
      active mammalian GPCRs in S. cerevisiae.

PMID- 19760667
TI  - Prediction of antibody response using recombinant human protein fragments as
      antigen.
AB  - A great need exists for prediction of antibody response for the generation of
      antibodies toward protein targets. Earlier studies have suggested that prediction
      methods based on hydrophilicity propensity scale, in which the degree of exposure
      of the amino acid in an aqueous solvent is calculated, has limited value. Here,
      we show a comparative analysis based on 12,634 affinity-purified antibodies
      generated in a standardized manner against human recombinant protein fragments.
      The antibody response (yield) was measured and compared to theoretical
      predictions based on a large number (544) of published propensity scales. The
      results show that some of the scales have predictive power, although the overall
      Pearson correlation coefficient is relatively low (0.2) even for the best
      performing amino acid indices. Based on the current data set, a new propensity
      scale was calculated with a Pearson correlation coefficient of 0.25. The values
      correlated in some extent to earlier scales, including large penalty for
      hydrophobic and cysteine residues and high positive contribution from acidic
      residues, but with relatively low positive contribution from basic residues. The
      fraction of immunogens generating low antibody responses was reduced from 30% to
      around 10% if immunogens with a high propensity score (>0.48) were selected as
      compared to immunogens with lower scores (<0.29). The study demonstrates that a
      propensity scale might be useful for prediction of antibody response generated by
      immunization of recombinant protein fragments. The data set presented here can be
      used for further studies to design new prediction tools for the generation of
      antibodies to specific protein targets.

PMID- 19760668
TI  - Psychometric evaluation and validation of the German version of the Acute Stress
      Disorder Scale across two distinct trauma populations.
AB  - Addressing the lack of self-report tools for acute stress disorder assessment,
      the authors aimed at translating and evaluating the Acute Stress Disorder Scale
      (ASDS) into German. The scale was applied to parents of children following
      cardiopulmonary bypass surgery (n = 61), and to patients with an acute cardiac
      event (n = 52) within one month of illness-related trauma. Indices of
      reliability, construct, and predictive validity with established measures of
      posttraumatic stress, anxiety, and depression suggest that the German ASDS is a
      psychometrically sound and valid instrument.

PMID- 19760670
TI  - Lymphadenectomy for patients with cervical cancer: is it of value?
AB  - INTRODUCTION: Discovery of positive lymph nodes (LNs) in patients with cervix
      cancer is important prognostically, may direct adjuvant therapy, and may have
      therapeutic benefit. The purpose of this Surveillance Epidemiology and End
      Results (SEER) analysis was to assess the value of lymphadenectomy (LND) in
      patients with cervical cancer. METHODS: The 17-registry SEER database was
      searched for patients treated for cervical cancer between 1988 and 1998. Observed
      survival (OS) and expected survival (ES) were reported with a minimum of 5-year
      follow-up. Chi-square analysis and log-rank test were used to compare OS and ES.
      RESULTS: Between 1988 and 1998, 4,059 of 12,882 patients underwent LND for
      cervical cancer and were registered. By stage, 2,653 of 7,621 stage I, 341 of
      2,042 stage II, 814 of 1,986 stage III, 251 of 1,233 stage IV, and 28 of 226
      stage IVA patients underwent LND. Of these, 778 stage III and 210 stage IV
      patients had a +LN. Patients who underwent LND had improved OS (P = 0.001). OS
      was significantly increased for each stage after LND. OS increased based on
      number of nodes resected. OS increased up to 15 nodes resected (P = 0.01).
      CONCLUSION: This SEER analysis of 12,882 patients suggests that LND benefited
      patients with cervical cancer and OS was improved.

PMID- 19760669
TI  - Genetic reduction of circulating insulin-like growth factor-1 inhibits
      azoxymethane-induced colon tumorigenesis in mice.
AB  - High levels of insulin-like growth factor-1 (IGF-1) have been associated with a
      significant increase in colon cancer risk. Additionally, IGF-1 inhibits apoptosis
      and stimulates proliferation of colonic epithelial cells in vitro. Unfortunately,
      IGF-1 knockout mice have severe developmental abnormalities and most do not
      survive, making it difficult to study how genetic ablation of IGF-1 affects colon
      tumorigenesis. To test the hypothesis that inhibition of IGF-1 prevents colon
      tumorigenesis, we utilized a preexisting mouse model containing a deletion of the
      igf1 gene in the liver through a Cre/loxP system. These liver-specific IGF-1
      deficient (LID) mice display a 50-75% reduction in circulating IGF-1 levels. We
      conducted a pilot study to assess the impact of liver-specific IGF-1 deficiency
      on azoxymethane (AOM)-induced colon tumors. LID mice had a significant inhibition
      of colon tumor multiplicity in the proximal area of the colon compared to their
      wild-type littermates. We examined markers of proliferation and apoptosis in the
      colons of the LID and wild-type mice to see if these were consistent with
      tumorigenesis. We observed a decrease in proliferation in the colons of the LID
      mice and an increase in apoptosis. Finally, we examined cytokine levels to
      determine whether IGF-1 interacts with inflammatory pathways to affect colon
      tumorigenesis. We observed a significant reduction in the levels of 7 out of 10
      cytokines that were measured in the LID mice as compared to wild-type
      littermates. Results from this pilot study support the hypothesis that reductions
      in circulating IGF-1 levels may prevent colon tumorigenesis and affect both
      proliferation and apoptosis. Future experiments will investigate downstream genes
      of the IGF-1 receptor.

PMID- 19760671
TI  - Effect of reactive-aldehydes on the modification and dysfunction of human serum
      albumin.
AB  - Advanced glycation end products (AGEs) are generated not only from glucose but
      also from several aldehydes such as methylglyoxal, glyoxal, and glycolaldehyde.
      The aim of the present study was to investigate the effect of several aldehydes
      on human serum albumin (HSA) in terms of the physicochemical properties and
      formation of AGE structures. HSA modified with methylglyoxal, generated by the
      glycolysis pathway and degradation of the Schiff base, showed the highest
      increase in the molecular weight and net negative charge, whereas glucose
      modification caused a small increase in the molecular weight even incubation for
      after 4 weeks. N(epsilon)-(carboxymethyl)lysine (CML), N(epsilon)
      (carboxyethyl)lysine (CEL), and imidazolone increased in modified HSA in
      correlation with their lysine and arginine modification, whereas high amounts of
      GA-pyridine was detected in HSA modified with glycolaldehyde. Furthermore, the
      binding ability of HSA to warfarin and ketoprofen was more effectively decreased
      by methylglyoxal modification than the other aldehydes. These results indicated
      that changes in the physicochemical properties and the formation of AGE
      structures are highly dependent on the aldehydes.

PMID- 19760672
TI  - Diaphragmatic involvement without bulbar dysfunction or features to suggest
      amyotrophic lateral sclerosis in brachial amyotrophic diplegia.

PMID- 19760673
TI  - Association of CHRN genes with "dizziness" to tobacco.
AB  - The neuronal nicotinic receptor genes (CHRN) have been implicated in a variety of
      smoking-related behaviors. Here we tested for association between an early
      subjective response phenotype, "dizziness," and 226 single nucleotide
      polymorphisms (SNPs) in CHRN genes. The sample included 789 nicotine-dependent
      cases and 811 controls, where early "dizziness" reports were significantly
      associated with case/control status (P < 0.0001). Multiple SNPs in the putative
      promoter region of the CHRNB3 gene were nominally associated with "dizziness"
      experience from the first few cigarettes (P < 0.01). Cell culture studies were
      conducted to examine the ability of different haplotypes in the CHRNB3 promoter
      to drive luciferase expression. Data from these experiments support the
      hypothesis that different alleles in the CHRNB3 upstream promoter region may lead
      to different levels of RNA expression. In addition, a novel finding of
      association between SNPs in the CHRNA10 gene reached experiment-wide empirical
      significance (P = 0.048), which implicates another CHRN gene as being involved in
      early subjective response to tobacco.

PMID- 19760674
TI  - No association of dysbindin with symptom factors of schizophrenia in an Irish
      case-control sample.
AB  - Robust associations between the dysbindin gene (DTNBP1) and schizophrenia have
      been demonstrated in many but not all samples, and evidence that this gene
      particularly predisposes to negative symptoms in this illness has been presented.
      The current study sought to replicate the previously reported negative symptom
      associations in an Irish case-control sample. Association between dysbindin and
      schizophrenia has been established in this cohort, and a factor analysis of the
      assessed symptoms yielded three factors, Positive, Negative, and Schneiderian.
      The sequential addition method was applied using UNPHASED to assess the
      relationship between these symptom factors and the high-risk haplotype. No
      associations were detected for any of the symptom factors indicating that the
      dysbindin risk haplotype does not predispose to a particular group of symptoms in
      this sample. Several possibilities, such as differing risk haplotypes, may
      explain this finding.

PMID- 19760675
TI  - G72 influences longitudinal change in frontal lobe volume in schizophrenia.
AB  - Schizophrenia is a neurodevelopmental psychiatric disorder characterized by a
      variety of structural brain abnormalities that appear to progress across the
      course of illness. Schizophrenia also is highly heritable, and one gene that has
      emerged as a possible susceptibility factor is G72. G72 influences brain
      development and activity by an as-yet unclear mechanism, and multiple studies
      have reported associations between G72 and schizophrenia. We were interested in
      linking these domains of investigation by determining whether G72 also influences
      the rate of longitudinal structural brain changes in individuals with
      schizophrenia. As part of the Iowa Longitudinal Study of Recent Onset Psychoses,
      we genotyped four G72 polymorphisms previously associated with schizophrenia in
      110 subjects with schizophrenia or schizoaffective disorder from whom we had
      obtained two brain MRI scans an average of 3 years apart. The four polymorphisms
      captured three haplotypes, one of which was strongly associated with an increased
      rate of frontal lobe volume decrement. This same haplotype was also associated
      with more severe psychotic symptoms at the time of the second scan. These data
      thus suggest that variation in G72 modulates the progressive brain changes that
      characterize schizophrenia.

PMID- 19760676
TI  - Volumetric and lateralized differences in selected brain regions of chimpanzees
      (Pan troglodytes) and bonobos (Pan paniscus).
AB  - The two species of Pan, bonobos and common chimpanzees, have been reported to
      have different social organization, cognitive and linguistic abilities and motor
      skill, despite their close biological relationship. Here, we examined whether
      bonobos and chimpanzee differ in selected brain regions that may map to these
      different social and cognitive abilities. Eight chimpanzees and eight bonobos
      matched on age, sex and rearing experiences were magnetic resonance images
      scanned and volumetric measures were obtained for the whole brain, cerebellum,
      striatum, motor-hand area, hippocampus, inferior frontal gyrus and planum
      temporale. Chimpanzees had significantly larger cerebellum and borderline
      significantly larger hippocampus and putamen, after adjusting for brain size,
      compared with bonobos. Bonobos showed greater leftward asymmetries in the
      striatum and motor-hand area compared with chimpanzees. No significant
      differences in either the volume or lateralization for the so-called language
      homologs were found between species. The results suggest that the two species of
      Pan are quite similar neurologically, though some volumetric and lateralized
      differences may reflect inherent differences in social organization, cognition
      and motor skills.

PMID- 19760677
TI  - Novel mutations in the calreticulin gene core promoter and coding sequence in
      schizoaffective disorder.
AB  - We have recently reported the first case of mutation in the core promoter
      sequence of the human calreticulin gene in a family case of schizoaffective
      disorder. Remarkably, this gene coincides with a region of suggested linkage at
      19p13.2, identified in a whole genome scan [Hamshere et al. (2005); Arch Gen
      Psychiatry 62;1081-1088]. The identified mutation was located at the conserved
      position -48 from the transcription start site, and was shown to be of functional
      effect, resulting in the aberrant expression of the gene. Following screening of
      the gene in 60 independent cases of schizoaffective disorder, we report novel
      germ-line mutations at positions -205 C > T and the conserved exon 5 (c: 682 C >
      T, pro228ser) in two unrelated cases of schizoaffective disorder. These mutations
      were disease-specific, and as for the -48 G > C mutation, neither was detected in
      a control population of 370 individuals, indicating a contribution of 3.17% in
      this sample series. To our knowledge, this is the first instance of disease
      specific mutations in schizoaffective disorder, which warrants systematic
      screening of the regulatory and coding regions of the calreticulin gene in this
      disorder.

PMID- 19760678
TI  - Reproductive toxicity of phthalate esters.
AB  - Phthalate esters are ubiquitous environmental contaminants that in general
      display low-toxicity. Overall, the reproductive effects of these compounds are
      well characterized in adult's animals, with gonadal injury observed after high
      dose exposure. However, results of recent transgeneration studies indicate that
      the reproductive system of developing animals is particularly vulnerable to
      certain phthalates. The phenotypic alterations observed in male offspring rats
      exposed during the perinatal period have remarkable similarities with common
      human reproductive disorders, including cryptorchidism, hypospadias and low-sperm
      counts. Recent results also indicate that high phthalate doses can adversely
      affect adult and developing female rats. However, the main question involving
      phthalates is whether the current level of human exposure is sufficient to
      adversely affect male and/or female reproductive health. Here, we review the
      reproductive toxicity data of phthalates in adult and developing animals as well
      as possible modes of action. In addition, we briefly discuss the relevance of
      animal studies to humans in light of recent epidemiological data and experimental
      research with low (human relevant) doses. Finally, we point out some critical
      issues that should be addressed in order to clarify the implications of
      phthalates for human reproduction.

PMID- 19760679
TI  - beta-Carotene and beta-cryptoxanthin but not lutein evoke redox and immune
      changes in RAW264 murine macrophages.
AB  - The mechanism of immunological benefits induced by carotenoids has not been fully
      elucidated. Here, we investigated some of the immunity-related properties of beta
      carotene and two other carotenoids, beta-cryptoxanthin, and lutein, on the murine
      macrophages cell line RAW264. beta-Carotene added to the culture medium
      accumulated in the cells in a time- and dose-dependent manner. The accumulation
      was positively correlated with cellular lipid peroxidation, demonstrating the pro
      oxidative activity of beta-carotene, and also with the synthesis of glutathione,
      an intracellular antioxidant. Conversely, accumulation of beta-carotene was
      negatively correlated with the transcription of immune-active molecules, such as
      IL-1beta, IL-6, and IL-12 p40, in cells stimulated by LPS and INF-gamma. The
      transcription of the pro-inflammatory cytokines IL-1beta and IL-6 was more
      sensitive to the accumulation of beta-carotene than was IL-12 p40. The
      accumulation of beta-cryptoxanthin in cells resulted in effects similar to those
      of beta-carotene. However, lutein accumulated minimally and did not significantly
      affect the cells. These results demonstrate that beta-carotene, and beta
      cryptoxanthin as well, can accumulate in RAW264 cells and induce changes in
      intracellular redox status, which in turn regulate the immune function of
      macrophages.

PMID- 19760680
TI  - Assessment of heat treatment of dairy products by MALDI-TOF-MS.
AB  - The formation of the Amadori product from lactose (protein lactosylation) is a
      major parameter to evaluate the quality of processed milk. Here, MALDI-TOF-MS was
      used for the relative quantification of lactose-adducts in heated milk. Milk was
      heated at a temperature of 70, 80, and 100 degrees C between 0 and 300 min,
      diluted, and subjected directly to MALDI-TOF-MS. The lactosylation rate of alpha
      lactalbumin increased with increasing reaction temperature and time. The results
      correlated well with established markers for heat treatment of milk
      (concentration of total soluble protein, soluble alpha-lactalbumin and beta
      lactoglobulin at pH 4.6, and fluorescence of advanced Maillard products and
      soluble tryptophan index; r=0.969-0.997). The method was also applied to examine
      commercially available dairy products. In severely heated products, protein pre
      purification by immobilized metal affinity chromatography improved spectra
      quality. Relative quantification of protein lactosylation by MALDI-TOF-MS proved
      to be a very fast and reliable method to monitor early Maillard reaction during
      milk processing.

PMID- 19760681
TI  - Metabolism and actions of conjugated linoleic acids on atherosclerosis-related
      events in vascular endothelial cells and smooth muscle cells.
AB  - Conjugated linoleic acids (CLAs) are biologically highly active lipid compounds
      that have attracted great scientific interest due to their ability to cause
      either inhibition of atherosclerotic plaque development or even regression of pre
      established atherosclerotic plaques in mice, hamsters and rabbits. The underlying
      mechanisms of action, however, are only poorly understood. Since cell culture
      experiments are appropriate to gain insight into the mechanisms of action of a
      compound, the present review summarizes data from cell culture studies about the
      metabolism and the actions of CLAs on atherosclerosis-related events in
      endothelial cells (ECs) and smooth muscle cells (SMCs), which are important cells
      contributing to atherosclerotic lesion development. Based on these studies, it
      can be concluded that CLAs exert several beneficial actions including inhibition
      of inflammatory and vasoactive mediator release from ECs and SMCs, which may help
      explain the anti-atherogenic effect of CLAs observed in vivo. The observation
      that significant levels of CLA metabolites, which have been reported to have
      significant biological activities, are well detectable in ECs and SMCs indicates
      that the anti-atherogenic effects observed with CLAs are presumably mediated not
      only by CLAs themselves but also by their metabolites.

PMID- 19760682
TI  - Development of a biologically inspired locomotion system for a capsule endoscope.
AB  - BACKGROUND: A capsule endoscope has a limited ability to obtain images of the
      digestive organs because its movement depends on peristaltic motion. To overcome
      this problem, capsule endoscopes require a propulsion system. METHODS: This paper
      proposes a propulsion system for a capsule endoscope that mimics the locomotive
      mechanism of snails and earthworms. The prototype crawler can elongate and
      contract itself longitudinally and adhere to a wall via suction cups. RESULTS: We
      investigated the effect of the inclination angle of the propulsion plane, the
      mucus viscosity between the propulsion plane and the crawler, and the stiffness
      of the propulsion plane on the locomotion of the prototype crawler. We found that
      the crawler could move on a rubber sheet and on inclined planes covered with
      mucus. We discussed advantages and limitations of the prototype crawler compared
      to the different locomotive systems developed in former studies. CONCLUSIONS: We
      believe that the prototype crawler provides a better understanding of the
      propulsion mechanism for use in the gastrointestinal tract.

PMID- 19760683
TI  - Epidemiologic features and clinical subgroups of anotia/microtia in Texas.
AB  - BACKGROUND: Few studies have investigated the epidemiologic features of
      clinically defined subgroups of anotia/microtia. METHODS: Data on cases of anotia
      and/or microtia among 1999-2005 deliveries were obtained from the Texas Birth
      Defects Registry, a population-based active surveillance system. We determined
      crude and adjusted associations between selected factors and seven clinical
      subgroups of anotia/microtia. RESULTS: In total, 742 cases were diagnosed with
      anotia and/or microtia, corresponding to a prevalence of 2.86 per 10,000 live
      births. Of those, 45% had no other major birth defect ("isolated"), 77% were
      unilateral, and 22% bilateral. Anotia alone made up 6%, whereas microtia made up
      94%. Birth prevalence was higher with increasing maternal age and among Mexico
      born Hispanics. Compared to white mothers, Hispanic mothers were two-to-three
      times more likely to have infants with all but the syndromic and bilateral groups
      (adjusted prevalence ratios [aPRs] = 2.05-2.61). Non-Hispanic blacks had
      significantly lower risk for total anotia/microtia, and for the isolated,
      unilateral, and microtia subgroups (aPRs = 0.42-0.64). Less educated mothers were
      three-to-four times more likely to have children with anotia (aPRs = 2.98 for
      less than high school, 3.97 for high school graduates). Males were more likely to
      be born with total anotia/microtia and with syndromic, unilateral, and microtia
      subtypes (aPRs = 1.27-1.41). CONCLUSIONS: In Texas, most anotia/microtia cases
      were in the unilateral and microtia groups, and 45% were isolated. Several
      clinical subgroups exhibited higher prevalence in males and among older mothers.
      Relative to whites, blacks were at lower risk and Hispanics (especially Mexico
      born mothers) were at higher risk for selected types of anotia/microtia.

PMID- 19760684
TI  - What controls the reactivity of 1,3-dipolar cycloadditions?

PMID- 19760685
TI  - Supramolecular stacking of doxorubicin on carbon nanotubes for in vivo cancer
      therapy.

PMID- 19760686
TI  - Switching the cubic nonlinear optical properties of an electro-, halo-, and
      photochromic ruthenium alkynyl complex across six states.

PMID- 19760687
TI  - Plasmon-mediated synthesis of silver triangular bipyramids.

PMID- 19760688
TI  - Tunable aryl alkyl ionic liquids (TAAILs): the next generation of ionic liquids.

PMID- 19760689
TI  - Iridium-catalyzed regio- and enantioselective N-allylation of indoles.

PMID- 19760690
TI  - Making epothilones fluoresce: design, synthesis, and biological characterization
      of a fluorescent N12-aza-epothilone (azathilone).
AB  - A green fluorescent 12-aza-epothilone (azathilone) derivative has been prepared
      through the attachment of the 4-nitro-2,1,3-benzoxadiazole (NBD) fluorophore to
      the 12-nitrogen atom of the azamacrolide core structure. While less potent than
      natural epothilones or different N12-acylated azathilone derivatives, NBD
      azathilone (3) promotes tubulin assembly, inhibits cancer cell proliferation in
      vitro and arrests the cell cycle at the G2/M transition. Most significantly, the
      binding of 3 to cellular microtubules (MTs) could be directly visualized by
      confocal fluorescence microscopy. Based on competition binding experiments with
      laulimalide-stabilized MTs in vitro, the N12-Boc substituted azathilone 1, Epo A,
      and NBD-azathilone (3) all interact with the same tubulin-binding site.
      Computational studies provided a structural model of the complexes between beta
      tubulin and 1 or 3, respectively, in which the NBD moiety of 3 or the BOC moiety
      of 1 directly and specifically contribute to MT binding. Collectively, these data
      demonstrate that the cellular effects of 3 and, by inference, also of other
      azathilones are the result of their interactions with the cellular MT network.

PMID- 19760691
TI  - SSB-assisted duplex invasion of preorganized PNA into double-stranded DNA.

PMID- 19760692
TI  - Phosphatidylethanolamine-binding proteins, including RKIP, exhibit affinity for
      phosphodiesterase-5 inhibitors.
AB  - Identifying protein "interactors" of drugs is of great importance to understand
      their mode of action and possible cross-reactivity to off-target protein binders.
      In this study, we profile proteins that bind to PF-3717842, a high-affinity
      phosphodiesterase-5 (PDE5) inhibitor, by using a refined affinity pulldown
      approach with PF-3717842 immobilized beads. By performing these pulldowns in rat
      testis tissue lysate, we strongly and specifically enriched for PDE5 and a few
      other PDEs. In addition to these expected affinity-enriched proteins we also
      detect rodent-specific phosphatidylethanolamine-binding protein 2 (PEBP2), as a
      putative binder to the PDE5 inhibitor. By using recombinant forms of the related
      murine mPEBP2, mPEBP1 and human hPEBP1 (also known as Raf kinase inhibitor
      protein or RKIP) we confirm that they all can bind strongly to immobilized as
      well as soluble PF-3717842. As the phosphatidylethanolamine-binding proteins are
      involved in various important signal transduction pathways, the synthetic PDE5
      inhibitor used here might form a platform to synthesize enhanced
      binders/inhibitors of the family of PEBP proteins. Our approach shows how
      chemical proteomics might be used to profile the biochemical space (interactome)
      of small molecule inhibitors.

PMID- 19760694
TI  - Real-time nanomicroscopy via three-dimensional single-particle tracking.
AB  - We developed a new method for real-time, three-dimensional tracking of
      fluorescent particles. The instrument is based on a laser-scanning confocal
      microscope where the focus of the laser beam is scanned or orbited around the
      particle. Two confocal pinholes are used to simultaneously monitor regions
      immediately above and below the particle and a feedback loop is used to keep the
      orbit centered on the particle. For moderate count rates, this system can track
      particles with 15 nm spatial resolution in the lateral dimensions and 50 nm in
      the axial dimension at a temporal resolution of 32 ms. To investigate the
      interaction of the tracked particles with cellular components, we have combined
      our orbital tracking microscope with a dual-color, wide-field setup. Dual-color
      fluorescence wide-field images are recorded simultaneously in the same image
      plane as the particle being tracked. The functionality of the system was
      demonstrated by tracking fluorescent-labeled artificial viruses in tubulin-eGFP
      expressing HUH7 cells. The resulting trajectories can be used to investigate the
      microtubule network with super resolution.

PMID- 19760695
TI  - Ultrasonic spectrometry of aqueous solutions of alkyl maltosides: kinetics of
      micelle formation and head-group isomerization.
AB  - At frequencies between 100 kHz and 400 MHz, ultrasonic attenuation spectra are
      measured at 25 degrees C for aqueous solutions of hexyl-, heptyl-, octyl-, nonyl
      , and decyl-beta-D-maltopyranoside as well as of decyl-alpha-D-maltopyranoside.
      The spectra with surfactant concentration c above the relevant critical micelle
      concentration (cmc) display three relaxation terms with discrete relaxation
      times. That with a relaxation time between 0.1 and 1.2 micros is due to exchange
      of monomers between micelles and the suspending phase. It is discussed in the
      light of the Teubner-Kahlweit-Aniansson-Wall model of the formation/decay
      kinetics of systems with Gaussian size distribution of micelles. The relaxation
      parameters are compared to those for solutions of other non-ionic surfactants,
      such as alkyl monoglycosides and poly(ethylene glycol) monoalkyl ethers. At c <
      cmc this low-frequency relaxation term is missing and at c approximately = cmc it
      is broadened, as is characteristic of solutions of oligomeric molecular
      structures rather than proper micelles. The relaxation terms with relaxation
      times between 6 and 15 ns and 0.7 and 2.3 ns reveal head-group rotations around
      glycosidic angles and isomerization of the exocyclic hydroxymethyl group,
      respectively. These unimolecular reactions are also examined with a view to
      solutions of alkyl monoglycosides as well as of glucose and maltose.

PMID- 19760696
TI  - Electrochemical behaviour of iron in a third-generation ionic liquid: cyclic
      voltammetry and micromachining investigations.
AB  - The electrochemical behaviour of Fe in 1-ethyl-3-methylimidazolium
      bis(trifluoromethylsulfonyl)imide ([Emim](+)Ntf2(-)) and mixtures with Cl(-) is
      studied with the aim of investigating the applicability of ionic liquids (IL) for
      the electrochemical machining of iron. Whereas in pure IL iron could not be
      significantly dissolved, the addition of Cl(-) enables the active dissolution
      with anodic current densities up to several mA cm(-2). Although several anodic
      peaks appear in the cyclic voltammograms (CV), the distinct assignment of those
      electrochemical processes remain difficult. In particular no proof for the
      formation of FeCl(x) (2-x) complexes during Fe dissolution are deduced from the
      CV, although such complexes are shown to be stable in the employed electrolyte.
      In addition, we present electrochemical drilling experiments with short potential
      pulses, which demonstrate that electrochemical machining of Fe is, in principle,
      possible in IL based electrolytes, even though hampered by slow machining speed.

PMID- 19760697
TI  - Axonal guidance by surface microstructuring for intracellular transport
      investigations.
AB  - Intracellular transport, a complex interplay of diverse processes, is fundamental
      for the development, function and survival of cells. Passive diffusion and active
      transport phases alternate in living cells, with active phases arising from
      molecular motors, such as kinesin or dynein, pulling cargoes along microtubules.
      A better understanding of stochasic mechanisms involved in motor-microtubule
      interactions and in diffusion processes, which enable efficient active transport
      over long distances in motor neurons, requires a better link between theoretical
      models and live-cell experiments. Herein, we establish one-dimensional (1D)
      intracellular transport geometries, suitable for comparing experimental findings
      with recent theoretical 1D model predictions, by guiding axonal outgrowth of
      pheochromocytoma (PC12) cells along predefined chemical surface structures with a
      strip width of 2 microm, fabricated by means of microscale plasma-initiated
      patterning (microPIP method). Quantification of the intracellular transport of
      quantum dots (QDs) in straight axons, which exhibit almost parallel microtubules,
      is obtained by our recently developed algorithm based on a time-resolved mean
      square displacement (MSD) analysis. Such a thorough dissection of experimental
      data will be useful for validation and clarification of current theoretical
      transport models.

PMID- 19760698
TI  - Photoactive nanostructures of polypyrrole.
AB  - The creation of nanostructures of the photoactive polymer polypyrrole (PPy) on
      glass substrates with the spin-coating method is described. No additional post
      production treatment is necessary to obtain uniformly distributed photoactive
      nanostructures on macroscopically scaled substrates. Based on X-ray reflectivity
      measurements, the critical solution concentration of PPy below which these
      nanostructures develop is determined. The PPy nanostructures are displayed with
      atomic force microscopy (AFM) measurements, which prove that the nanostructures
      form directly on the substrate. With UV/Vis spectroscopy the absorption behavior
      of the nanostructures is probed in comparison to PPy films and PPy solutions. A
      linear dependence of the absorption of the nanostructure on the surface coverage
      measured with AFM is detected. The influence of confinement on the conjugation
      length results in a modified absorption behavior of the nanostructures.

PMID- 19760699
TI  - Aryloxy phosphoramidate triesters: a technology for delivering monophosphorylated
      nucleosides and sugars into cells.
AB  - Prodrug technologies aimed at delivering nucleoside monophosphates into cells
      (protides) have proved to be effective in improving the therapeutic potential of
      antiviral and anticancer nucleosides. In these cases, the nucleoside
      monophosphates are delivered into the cell, where they may then be further
      converted (phosphorylated) to their active species. Herein, we describe one of
      these technologies developed in our laboratories, known as the phosphoramidate
      protide method. In this approach, the charges of the phosphate group are fully
      masked to provide efficient passive cell-membrane penetration. Upon entering the
      cell, the masking groups are enzymatically cleaved to release the phosphorylated
      biomolecule. The application of this technology to various therapeutic
      nucleosides has resulted in improved antiviral and anticancer activities, and in
      some cases it has transformed inactive nucleosides to active ones. Additionally,
      the phosphoramidate technology has also been applied to numerous antiviral
      nucleoside phosphonates, and has resulted in at least three phosphoramidate-based
      nucleotides progressing to clinical investigations. Furthermore, the
      phosphoramidate technology has been recently applied to sugars (mainly
      glucosamine) in order to improve their therapeutic potential. The development of
      the phosphoramidate technology, mechanism of action and the application of the
      technology to various monophosphorylated nucleosides and sugars will be reviewed.

PMID- 19760700
TI  - Chemistry as a prism: a review of light-emitting materials having tunable
      emission wavelengths.
AB  - Photoluminescent materials have been extensively applied in various fields of
      science because of their numerous advantages, such as excellent sensitivity, good
      specificity, a large linear range of analysis, ease of handling, and so on. Many
      strategies have been used to understand and manipulate the photophysical
      properties of photoluminescent materials. This Focus Review describes recent
      progress focused on tuning the photophysical properties, especially the emission
      wavelengths of pi-conjugated oligomers, photoluminescent organometallic
      complexes, and fluorescent organic dyes by chemical modification.

PMID- 19760701
TI  - Synthesis and photophysics of core-substituted naphthalene diimides: fluorophores
      for single molecule applications.
AB  - The synthesis and photophysics of two new aminopropenyl naphthalene diimide
      (SANDI) dyes are reported. A general and convenient method for the synthesis of
      the precursor mono-, di-, and tetrabrominated 1,4,5,8-naphthalene tetracarboxylic
      dianhydrides is described. The two core-substituted SANDIs exhibit many of the
      photophysical properties required for fluorescence labeling applications
      including high photostability and high fluorescence quantum yields (>0.5) in the
      visible region of the spectrum. The emission wavelength is sensitive to the
      number of substituents on the NDI core, and the fluorescence decay times are in
      the range of approximately 8-12 ns for both compounds in the solvents
      investigated. Preliminary fluorescence emission data from single molecules of the
      compounds embedded in poly(methyl methacrylate) films are also reported and show
      that single molecules have very low yields of photobleaching, particularly the di
      substituted system. Furthermore, only a small proportion (<10 %) of the single
      molecules studied display fluorescence intermittencies or "blinks" in their
      photon trajectory. The compounds appear to be excellent candidates for
      applications at the single molecule level, for example, as FRET labels.

PMID- 19760702
TI  - Biomass into chemicals: aerobic oxidation of 5-hydroxymethyl-2-furfural into 2,5
      furandicarboxylic acid with gold nanoparticle catalysts.
AB  - 5-hydroxymethyl-2-furfural is selectively converted into 2,5-furandicarboxylic
      acid (99 mol % yield) in water, under mild conditions (65-130 degrees C, 10 bar
      air) with gold nanoparticles supported on nanoparticulate ceria (Au-CeO(2)) and
      on titania (Au-TiO(2)); the former being more active and selective. A reaction
      mechanism is established and the rate-limiting step of the reaction is the
      alcohol oxidation of 5-hydroxymethyl-2-furancarboxylic acid into 2,5
      furandicarboxylic acid. The effects of pressure, temperature, substrate-to
      catalyst ratio, and amount of base are studied to find the most suitable reaction
      conditions. The absence of metal leaching is verified by chemical analysis of the
      reaction solution and by confirming that the reaction does not occur after
      catalyst removal by filtration in hot water. Substrate degradation is strongly
      diminished and the catalyst life increased by performing the reaction in two
      temperature steps.

PMID- 19760703
TI  - Physicochemical properties of ionic clathrate hydrates.
AB  - Ionic clathrate hydrates are known to be formed by the enclathration of
      hydrophobic cations or anions into confined cages and the incorporation of
      counterions into the water framework. As the ionic clathrate hydrates are
      considered for their potential applicability in various fields, including those
      that involve solid electrolytes, gas separation, and gas storage, numerous
      studies of the ionic clathrate hydrates have been reported. This review
      concentrates on the physicochemical properties of the ionic clathrate hydrates
      and the notable characteristics of these materials regarding their potential
      application are addressed.

PMID- 19760704
TI  - Benzo[b]phosphole-containing pi-electron systems: synthesis based on an
      intramolecular trans-halophosphanylation and some insights into their properties.
AB  - The intramolecular trans-halophosphanylation of 2
      (aminophosphanyl)phenylacetylenes mediated by PBr3 followed by the oxidation with
      H2O2, produces 3-bromobenzo[b]phosphole oxide derivatives. This cyclization is
      also used for the synthesis of a 3-iodo derivative by conducting the reaction in
      the presence of LiI. Based on this synthetic method, various benzophosphole
      containing pi-conjugated compounds, including a phosphoryl and methylene-bridged
      stilbene 10, 2,3,6,7-tetraphenylbenzo[1,2-b:4,5-b']diphosphole-P,P'-dioxides 11,
      and their phosphine sulfide derivatives 12, are synthesized. The study of the
      structure-property relationships in a series of the bridged stilbenes, including
      a bis(methylene)-bridged stilbene 10, and a bis(phosphoryl)-bridged stilbene,
      reveals that as the contribution of the phosphoryl groups increased, the
      absorption and emission maxima substantially shift to longer wavelengths. The
      intrinsic substituent effects of the phosphoryl group in this skeleton are to
      decrease the oscillator strength of the electronic transition and thus decrease
      the radiative decay rate constants from the singlet excited state. Nevertheless,
      these compounds maintain high fluorescence quantum yields (Phi(F)>0.8) owing to
      the significantly retarded nonradiative decay process. In the study of the
      benzodiphosphole derivatives 11 and 12, their cyclic voltammetry revealed that
      both of the phosphoryl and phosphine sulfide derivatives have low reduction
      potentials (-1.7 to -1.8 V vs ferrocene/ferrocenium couple) with the high
      reversibility of the redox waves. These compounds also showed high thermal
      stabilities with the high glass transition temperatures of 147-159 degrees C,
      indicative of their potential utilities as amorphous materials.

PMID- 19760705
TI  - Pressure-induced consecutive phase transitions of a metallic MMX-chain complex,
      Pt2(dtp)4I (dtp: C2H5CS2-).

PMID- 19760706
TI  - Periodic mesoporous organosilicas with helical and concentric circular pore
      architectures.
AB  - This study systematically investigates periodic mesoporous organosilicas (PMOs)
      with controlled helical and concentric circular (CC) pore architectures prepared
      through a basic-catalyzed sol-gel process by using an achiral cationic surfactant
      trimethyloctadecylammonium bromide (C(18)TAB) as a structure-directing agent,
      perfluorooctanoic acid (PFOA) as an additive, and 1,2-bis(triethoxysilyl)ethane
      (BTEE) as a hybrid silica precursor. By increasing the weight ratio of
      PFOA/C(18)TAB, a pore architecture transition of PMO materials from hexagonal
      arrayed, straight longitudinal channels to helical and CC mesostructures is
      achieved; such a transition has not been observed before in PMO materials. Our
      discovery is helpful in understanding the supramolecular cooperative assembly of
      hybrid materials and their structural and morphological evolution, which are
      important in the future applications of PMO materials.

PMID- 19760707
TI  - Experimental and theoretical study of tunable 1,3-lithium shift of
      propargylic/allenylic species, transmetallation, and Pd-catalyzed cross-coupling
      reactions.
AB  - The highly selective tuning of the isomerization from 1-arylalka-1,2-dien-1
      yllithium to 1-arylalka-1,2-dien-3-yllithium has been realized in the
      deprotonation of 1-arylalk-1-yne (conditions A and B) and carbolithiation of 1
      arylbut-3-en-1-yne with alkyllithium (conditions C and D). Subsequent
      transmetallation and Pd-catalyzed Negishi coupling reactions afforded 1,1-diaryl
      or 1,3-diaryl allenes with high selectivity. Deuterium-labeling cross experiments
      indicated that an intermolecular lithiation process occurred in both 1,3-lithium
      shift conditions (conditions B and D). 1-Arylalka-1,2-diene was confirmed
      experimentally to be the intermediate. A computational study at the B3LYP level
      for the isomerization indicated that the acidity of H at the 3-position is higher
      than that of the H at the 1-position of 1-phenyl-1,2-butadiene. Under conditions
      B, iPr(2)NH acts as a proton carrier to finish the 1,3-lithium shift. The overall
      activation barrier for the rate-determining step in the solvated models is
      approximately 21.0 kcal mol(-1), indicating that the isomerization is reasonable
      at room temperature. For the isomerization under conditions D, DFT calculations
      indicated that the addition of TMEDA (tetramethylethylenediamine) and HMPA
      (hexamethylphosphoramide) changes the global minimum of the system; among the
      possible mechanisms (P1-P5) considered, the mechanism catalyzed by dilithiated
      species (P5) is the most probable one. The overall activation barriers for
      isomerization in THF and TMEDA solvated models are 22.6 and 19.7 kcal mol(-1),
      respectively, proving that the isomerization may proceed at RT in THF or at -78
      degrees C with TMEDA, due to the fact that the solvation of the additives may
      increase the concentration of 1-phenyl-1,2-butadienyllithium monomer by a
      deaggregation effect.

PMID- 19760708
TI  - Theoretical study on the role of surface basicity and lewis acidity on the
      etherification of glycerol over alkaline earth metal oxides.
AB  - Alkaline earth metal oxides (MO) are catalytically active in the etherification
      of glycerol. Density Functional Theory (DFT) calculations have been used to
      examine the reactivity of glycerol with MO surfaces with M=Mg, Ca, Sr or Ba. More
      specifically, the optimum glycerol adsorption mode and the strength of glycerol
      interaction with regular MO (001) surfaces and a stepped CaO surface have been
      investigated and involves the interaction with acid-base surface sites. The
      basicity of lattice oxygen atoms is correlated with the adsorption energy: BaO (
      3.02 eV) > SrO (-2.85 eV) > CaO (-2.05 eV) > MgO (-1.35 eV). The interactions
      have an exothermic character, that is, the more basic the alkaline earth metal
      oxide, the more exothermic is the adsorption process and the higher the
      dissociation extent. Thus, the dissociation of glycerol increases in the order:
      MgO (not dissociated) < CaO (partially dissociated < SrO (partially dissociated)
      < BaO (completely dissociated). The presence of defects is found to play a key
      role in the mechanism: glycerol interaction with a stepped CaO surface presents
      the highest adsorption energy (-3.78 eV), and the molecule is found to dissociate
      at the step. The calculated structural parameters are found to be in good
      agreement with experimental data on catalyst reactivity. Moreover, the earlier
      postulated reaction mechanism, which also involves the additional involvement of
      Lewis acid sites proved to be feasible for CaO and SrO regular surfaces, and for
      the stepped CaO surface. It was found that for these oxides one of the most
      favored adsorption modes involves a non-dissociative adsorption of one hydroxyl
      group of glycerol, which as a result becomes a better leaving group. Therefore,
      theoretical evidence was found for the possible direct involvement of Lewis acid
      sites in the catalytic etherification of bio-derived alcohols, such as glycerol,
      as it is anticipated that these observations can be extended to sugar alcohols as
      well.

PMID- 19760709
TI  - Heterospin single-molecule magnets based on terbium ions and TCNQF(4) radicals:
      interplay between single-molecule magnet and phonon bottleneck phenomena
      investigated by dilution studies.
AB  - A series of isostructural compounds with formula
      [M(TCNQF(4))(2)(H(2)O)(6)]TCNQF(4)3 H(2)O (M=Tb (1), Y (2), Y:Tb (74:26) (3), and
      Y:Tb (97:3) (4); TCNQF(4)= tetrafluorotetracyanoquinodimethane) were prepared and
      their magnetic properties investigated. Compounds 1, 3, and 4 show the beginning
      of a frequency-dependent out-of-phase ac signal, and decreasing intensity of the
      signal with decreased concentration of Tb(III) ions in the diluted samples is
      observed. No out-of-phase signal was observed for 2, an indication that the
      behavior of 1, 3, and 4 is indicative of slow paramagnetic relaxation of Tb(III)
      ions in the samples. A more detailed micro-SQUID study at low temperature
      revealed an interplay between single-molecule magnetic (SMM) behavior and a
      phonon bottleneck (PB) effect, and that these properties depend on the
      concentration of diamagnetic yttrium ions. A combination of SMM and PB phenomena
      was found for 1, whereby the PB effect increases with increasing dilution until
      eventually a pure PB effect is observed for 2. The PB behavior is interpreted as
      being due to the presence of a "sea of organic S=1/2 radicals" from the TCNQF(4)
      radicals in these compounds. The present data underscore the fact that the
      presence of an out-of-phase ac signal may not, in fact, be caused by SMM
      behavior, particularly when magnetic metal ions are combined with organic radical
      ligands such as those found in the organocyanide family.

PMID- 19760710
TI  - Controlling the conformational changes in donor-acceptor [4]-dendralenes through
      intramolecular charge-transfer processes.
AB  - The synthesis of two [4]-dendralene compounds incorporating thiophene-(p
      nitrophenyl) donor-acceptor units is presented. The dendralenes adopt two
      different conformers in solution and solid state and the transformation between
      the structures can be controlled by light and heat. The electron-donating
      components of the dendralenes are represented by bromothienyl (in 13) and
      ethylenedioxythiophene(EDOT)-thienyl (in 15) end-groups. The most facile
      transformation involves the isomerisation of donor-acceptor conjugated systems (a
      conformers) into structures in which only the thiophenes are conjugated (b
      conformers), and this process is driven by ambient light. The structures of the
      two conformers of compound 13 are confirmed by single-crystal X-ray diffraction
      studies and the structural changes in both compounds have been monitored by 1H
      NMR spectroscopy and absorption studies. The transformations were found to be
      first-order processes with rate constants of k=0.0027 s(-1) and k=0.00022 s(-1)
      for 13 and 15, respectively. Density functional theory calculations at the
      B3LYP/6-31G* level give credence to the proposed mechanism for the a-->b
      conversion, which involves photoinduced intramolecular charge transfer (ICT) as
      the key step. The EDOT derivative (15) can be polymerised by electrochemical
      oxidation and a combination of cyclic voltammetry and UV/Vis
      spectroelectrochemical experiments indicate that the a conformer can be trapped
      and stabilised in the solid state.

PMID- 19760711
TI  - ESIMS studies and calculations on alkali-metal adduct ions of ruthenium olefin
      metathesis catalysts and their catalytic activity in metathesis reactions.
AB  - Electrospray ionization mass spectrometry (ESIMS) and subsequent tandem mass
      spectrometry (MS/MS) analyses were used to study some important metathesis
      reactions with the first-generation ruthenium catalyst 1, focusing on the
      ruthenium complex intermediates in the catalytic cycle. In situ cationization
      with alkali cations (Li(+), Na(+), K(+), and Cs(+)) using a microreactor coupled
      directly to the ESI ion source allowed mass spectrometric detection and
      characterization of the ruthenium species present in solution and particularly
      the catalytically active monophosphine-ruthenium intermediates present in
      equilibrium with the respective bisphosphine-ruthenium species in solution.
      Moreover, the intrinsic catalytic activity of the cationized monophosphine
      ruthenium complex 1 aK(+) was directly demonstrated by gas-phase reactions with 1
      butene or ethene to give the propylidene Ru species 3 aK(+) and the methylidene
      Ru species 4 aK(+), respectively. Ring-closing metathesis (RCM) reactions of 1,6
      heptadiene (5), 1,7-octadiene (6) and 1,8-nonadiene (7) were studied in the
      presence of KCl and the ruthenium alkylidene intermediates 8, 9, and 10,
      respectively, were detected as cationized monophosphine and bisphosphine
      ruthenium complexes. Acyclic diene metathesis (ADMET) polymerization of 1,9
      decadiene (14) and ring-opening metathesis polymerization (ROMP) of cyclooctene
      (18) were studied analogously, and the expected ruthenium alkylidene
      intermediates were directly intercepted from reaction solution and characterized
      unambiguously by their isotopic patterns and ESIMS/MS. ADMET polymerization was
      not observed for 1,5-hexadiene (22), but the formation of the intramolecularly
      stabilized monophosphine ruthenium complex 23 a was seen. The ratio of the signal
      intensities of the respective with potassium cationized monophosphine and
      bisphosphine alkylidene Ru species varied from [I(4a)]/[I(4)]=0.02 to
      [I(23a)]/[I(23)]=10.2 and proved to be a sensitive and quantitative probe for
      intramolecular pi-complex formation of the monophosphine-ruthenium species and of
      double bonds in the alkylidene chain. MS/MS spectra revealed the intrinsic
      metathesis catalytic activity of the potassium adduct ions of the ruthenium
      alkylidene intermediates 8 a, 9 a, 10 a, 15 a, and 19 a, but not 23 a by
      elimination of the respective cycloalkene in the second step of RCM. Computations
      were performed to provide information about the structures of the alkali metal
      adduct ions of catalyst 1 and the influence of the alkali metal ions on the
      energy profile in the catalytic cycle of the metathesis reaction.

PMID- 19760712
TI  - An organocatalytic asymmetric tandem reaction for the construction of bicyclic
      skeletons.
AB  - Cyclic ketones react with (E)-2-nitroallylic acetates in the presence of
      catalytic pyrrolidine-thiourea, which affords bicyclic skeletons with four or
      five stereocenters in one single reaction with up to 98 % ee in moderate to high
      yields. The cooperative effects of both enamine and the Bronsted acid are found
      to be crucial for the high reactivity and enantioselectivity of this cascade
      reaction, which is demonstrated by both theoretical calculation and experimental
      data.

PMID- 19760713
TI  - Electronic structure and redox properties of metal nitride endohedral fullerenes
      M(3)N@C(2n) (M=Sc, Y, La, and Gd; 2n=80, 84, 88, 92, 96).
AB  - An extensive study of the redox properties of metal nitride endohedral fullerenes
      (MNEFs) based on DFT computational calculations has been performed. The
      electronic structure of the singly oxidized and reduced MNEFs has been thoroughly
      analyzed and the first anodic and cathodic potentials, as well as the
      electrochemical gaps, have been predicted for a large number of M(3)N@C(2n)
      systems (M=Sc, Y, La, and Gd; 2n=80, 84, 88, 92, and 96). In particular,
      calculations that include thermal and entropic effects correctly predict the
      different anodic behavior of the two isomers (I(h) and D(5h)) of Sc(3)N@C(80),
      which is the basis for their electrochemical separation. Important differences
      were found in the electronic structure of reduced M(3)N@C(80) when M=Sc or when M
      is a more electropositive metal, such as Y or Gd. Moreover, the changes in the
      electrochemical gaps within the Gd(3)N@C(2n) series (2n=80, 84, and 88) have been
      rationalized and the use of Y-based computational models to study the Gd-based
      systems has been justified. The redox properties of the largest MNEFs
      characterized so far, La(3)N@C(2n) (2n=92 and 96), were also correctly predicted.
      Finally, the quality of these predictions and their usefulness in distinguishing
      the carbon cages for MNEFs with unknown structures is discussed.

PMID- 19760714
TI  - A new cyanofluorene-triphenylamine copolymer: synthesis and photoinduced
      intramolecular electron transfer processes.
AB  - A new pi-conjugated copolymer, namely, poly{cyanofluore-alt-[5-(N,N'
      diphenylamino)phenylenevinylene]} ((CNF-TPA)(n)), was synthesized by condensation
      polymerization of 2,2'-(9,9-dioctyl-9H-fluorene-2,7-diyl)diacetonitrile and 5
      (N,N'-diphenylamino)benzene-1,3-dicarbaldehyde by using the Knoevenagel reaction.
      By design, diphenylamine, alkylfluorene and poly(p-phenylenevinylene) linkages
      were combined to form a (CNF-TPA)(n) copolymer which exhibits high thermal
      stability and glass-transition temperature. Photodynamic measurements in polar
      benzonitrile indicate fast and efficient photoinduced electron transfer (
      approximately 10(11) s(-1)) from triphenylamine (TPA) to cyanofluorene (CNF) to
      produce the long-lived charge-separated state (90 mus). The finding that the
      charge-recombination process of (CNF(.-)-TPA(.+))(n) is much slower than the
      charge separation in polar benzonitrile suggests a potential application in
      molecular-level electronic and optoelectronic devices.

PMID- 19760715
TI  - Gold- or platinum-catalyzed cascade processes of alkynol derivatives involving
      hydroalkoxylation reactions followed by Prins-type cyclizations.
AB  - An efficient method for the synthesis of [3.3.1]bicyclic compounds from easily
      available alkynol derivatives has been developed. The reaction is based on a gold
      or platinum-catalyzed tandem process that involves an intramolecular
      hydroalkoxylation of a triple bond followed by a Prins-type cyclization. The
      reaction has been carried out with differently substituted alkynol derivatives
      and oxygen-, nitrogen-, and carbon-centered nucleophiles. The incorporation of
      halogen atoms as nucleophiles and elimination reactions has also been studied.
      Enantiomerically pure [3.3.1]bicyclic systems were easily synthesized from the
      chiral pool.

PMID- 19760716
TI  - Self-assembled supramolecular nanocarrier hosting two kinds of guests in the site
      isolation state.
AB  - Hyperbranched polyethylenimine (HPEI) was simply mixed with a solution of
      amphiphilic calix[4]arene (AC4), which possesses four phenol groups and four
      aliphatic chains, in chloroform. This resulted in the novel supramolecular
      complex HPEI-AC4 through the noncovalent interaction of the amino groups of HPEI
      with the phenol groups of AC4. The formed HPEI-AC4 supramolecular complexes were
      characterized by 1H NMR spectroscopy and dynamic light scattering. The cationic
      water-soluble dye methyl blue (MB) and the anionic water-soluble dye methyl
      orange (MO) were used as the model guests to test the performance of HPEI-AC4 as
      a supramolecular nanocarrier. It was found that HPEI-AC4 could accommodate the
      anionic water-soluble MO guests into the HPEI core. The MO encapsulation capacity
      of HPEI-AC4 was pH sensitive, which reached maximum loading under weakly acidic
      conditions. The loaded MO molecules could be totally released when the pH value
      was reduced to be around 4.5 or raised to be around 9.5, and this process was
      reversible. HPEI-AC4 could not only accommodate the anionic MO with the HPEI core
      but could also simultaneously load the cationic MB molecules using the formed AC4
      shell, thereby realizing the site isolation of the two kinds of functional units.
      The amount of MO and MB encapsulated by HPEI-AC4 could be controlled by varying
      the ratio of hydroxyl groups of AC4 to amino groups of HPEI.

PMID- 19760717
TI  - Homoleptic organoderivatives of high-valent nickel(III).
AB  - Homoleptic perhalophenyl derivatives of divalent nickel complexes with the
      general formula [NBu(4)](2)[Ni(II)(C(6)X(5))(4)] [X=F (1), Cl (2)] have been
      prepared by low-temperature treatment of the halo-complex precursor
      [NBu(4)](2)[NiBr(4)] with the corresponding organolithium reagent LiC(6)X(5).
      Compounds 1 and 2 are electrochemically related by reversible one-electron
      exchange processes with the corresponding organometallate(III) compounds
      [NBu(4)][Ni(III)(C(6)X(5))(4)] [X=F (3), Cl (4)]. The potentials of the
      [Ni(III)(C(6)X(5))(4)](-)/[Ni(II)(C(6)X(5))(4)](2-) couples are +0.07 and -0.11 V
      for X=F or Cl, respectively. Compounds 3 and 4 have also been prepared and
      isolated in good yield by chemical oxidation of 1 or 2 with bromine or the
      amminium salt [N(C(6)H(4)Br-4)(3)][SbCl(6)]. The [Ni(III)(C(6)X(5))(4)](-)
      species have SP-4 structures in the salts 3 and 4, as established by single
      crystal X-ray diffraction methods. The [Ni(II)(C(6)F(5))(4)](2-) ion in the
      parent compound 1 has also been found to exhibit a rather similar SP-4 structure.
      According to their SP-4 geometry, the Ni(III) compounds (d(7)) behave as S=1/2
      systems both at microscopic (EPR) and macroscopic levels (ac and dc magnetization
      measurements). The spin Hamiltonian parameters obtained from the analysis of the
      magnetic behavior of 3 and 4 within the framework of ligand field theory show
      that the unpaired electron is centered mainly on the metal atom, with >97 %
      estimated d(z(2) ) contribution. Thermal decomposition of 3 and 4 proceeds with
      formation of the corresponding C(6)X(5)--C(6)X(5) coupling compounds.

PMID- 19760718
TI  - On the helical motif of the complexes created by association of helix-forming
      schizophyllan (SPG) and helix-forming polythiophene derivatives.
AB  - pi-Conjugated polymers can finely tune their electrical and optical properties in
      response to their conformational changes. We believe that a deeper understanding
      of their higher-order structures will stimulate further development of their
      applications. We had revealed that one helix-forming natural polysaccharide (SPG)
      and one polythiophene derivative (PT-1) formed a stable one-dimensional complex
      and in the polythiophene main chain a helical conformation was induced through
      the dynamic conformational changes. The objective of our present research is to
      obtain a better mechanistic understanding on the interaction between SPG and
      polythiophenes. Here we have used particular left- and right-handed helix-forming
      polythiophene derivatives (D- and L-POWTs, respectively) and studied their
      influence on the helical motif of the complexes. We observed that SPG interacts
      with both D- and L-POWTs through their dynamic conformational changes and both D-
      and L-POWTs form the right-handed co-helical complexes with SPG according to the
      inherent helical motif of SPG. In addition, it was confirmed that 1) the
      complexes do not coagulate in aqueous solution, and 2) the exchange in the
      helical motif can occur only when the polymers experience the denature-renature
      process. We believe, therefore, that the mechanism of the helical induction of
      the SPG/POWT complexes is very unique, being different from conventional
      equilibrium reactions.

PMID- 19760719
TI  - Rhodamine spiroamides for multicolor single-molecule switching fluorescent
      nanoscopy.
AB  - The design, synthesis, and evaluation of new rhodamine spiroamides are described.
      These molecules have applications in optical nanoscopy based on random switching
      of the fluorescent single molecules. The new markers may be used in
      (co)localization studies of various objects and their (mutual) positions and
      shape can be determined with a precision of a few tens of nanometers. Multicolor
      staining, good photoactivation, a large number of emitted photons, and selective
      chemical binding with amino or thiol groups were achieved due to the presence of
      various functional groups on the rhodamine spiroamides. Rigidized sulfonated
      xanthene fragment fused with six-membered rings, N,N'-bis(2,2,2-trifluoroethyl)
      groups, and a combination of additional double bonds and sulfonic acid groups
      with simple aliphatic spiroamide residue provide multicolor properties and
      improve performance of the rhodamine spiroamides in photoactivation and
      bioconjugation reactions. Having both essential parts of the photoswitchable
      assembly-the switching and the fluorescent (reporter) groups-combined in one
      chemical entity make this approach attractive for further development. A series
      of rhodamine spiroamides is presented along with characterizations of their most
      relevant properties for application as fluorescent probes in single-molecule
      switching and localization microscopy. Optical images with resolutions on the
      nanometer scale illustrate the potential of the labels in the colocalization of
      biological objects and the two-photon activation technique with optical
      sectioning.

PMID- 19760720
TI  - Improving the trapping of superoxide radical with a beta-cyclodextrin- 5
      diethoxyphosphoryl-5-methyl-1-pyrroline-N-oxide (DEPMPO) conjugate.

PMID- 19760721
TI  - Synthesis and reactivity of enantiomerically enriched thiiranium ions.
AB  - Enantiomerically enriched thiiranium ion 5 has been prepared by silver-assisted
      ionization of chloro sulfide 4 at -20 degrees C. This thiiranium ion is
      configurationally stable in solution up to room temperature as demonstrated by
      the stereospecific capture of the ion by various oxygen- and nitrogen-based
      nucleophiles. Both isolated olefins and weak Lewis bases can promote the
      racemization of 5 but these processes can also be suppressed at low temperature.
      Capture of 5 by methanol is faster than the racemization processes.

PMID- 19760722
TI  - Functionalization and rearrangement of spirocyclohexadienyl oxindoles:
      experimental and theoretical investigations.
AB  - The preparation and functionalization of spirocyclohexa-2,5-diene oxindoles is
      described. The spirocyclic core of the title compounds was installed by using a
      SmI(2)-mediated cyclization of aryl iodobenzamides. Epoxidation with CF(3)CO(3)H
      was then carried out and was shown to occur with a high level of
      diastereocontrol: the reagent approaches the diene moiety syn to the amide group,
      which is likely to be as a consequence of hydrogen bonding between the amide C=O
      bond and the peracid hydrogen. Carbanionic functionalization of the
      spirocyclohexa-2,5-diene oxindoles was then examined, leading to an unprecedented
      rearrangement of the strained spiro system into dearomatized phenanthridinones.
      Upon treatment with lithium diisopropylamide (LDA) at -40 degrees C, the dienes
      rearranged to provide a phenanthridinone lithium enolate intermediate that was
      trapped by electrophiles including alkyl halides and aldehydes. Interestingly,
      alkylation and hydroxyalkylation occurred with different regiocontrol. DFT
      calculations were performed that rationalize the observed skeleton rearrangement,
      emphasizing the role of LDA/diisopropylamine in this rearrangement. The proposed
      mechanism thus relies on a thermodynamically driven diisopropylamine-mediated
      proton transfer with the cleavage of the diene-amide C=O bond as the key step.

PMID- 19760723
TI  - The incorporation of indigo molecules in sepiolite tunnels.
AB  - Evidence for access of molecules the size of acetone or pyridine to the
      intracrystalline tunnels of nanofibre clay (sepiolite) has indicated formation of
      a new type of organic-inorganic nanocomposites. However, the introduction of
      larger molecules has been a recurring problem. It is now agreed that for indigo,
      the molecules are located on the external surface and at the ends of the fibres,
      thus blocking access to internal tunnels. We claim, however, that it is possible
      for indigo molecules to access the internal channels of sepiolite. FTIR and XRD
      analyses have provided evidence for folding of the sepiolite structure preheated
      at high temperature (above 350 degrees C). By comparison, we have shown that for
      indigo/sepiolite mixtures treated in the same conditions, no change in the
      crystalline structure of the sepiolite is observed, and that blue samples,
      related to Maya blue, with indigo molecules incorporated deeply enough into
      sepiolite to prevent folding of the tunnels, can be obtained. NMR, FTIR and
      thermal analysis confirm the interaction of indigo with the water coordinated to
      magnesium(II) and located inside the internal and external channels of sepiolite.
      Two other hypotheses are excluded; we show both that zeolitic water is not
      blocked in the tunnels by indigo, and that if thermal decomposition products of
      indigo can be formed, they are in a minority.

PMID- 19760724
TI  - Modification of supramolecular binding motifs induced by substrate registry:
      formation of self-assembled macrocycles and chain-like patterns.
AB  - The self-assembly properties of two Zn(II) porphyrin isomers on Cu(111) are
      studied at different coverage by means of scanning tunneling microscopy (STM).
      Both isomers are substituted in their meso-positions by two voluminous 3,5
      di(tert-butyl)phenyl and two rod-like 4'-cyanobiphenyl groups, respectively. In
      the trans-isomer, the two 4'-cyanobiphenyl groups are opposite to each other,
      whereas they are located at right angle in the cis-isomer. For coverage up to one
      monolayer, the cis-substituted porphyrins self-assemble to form oligomeric
      macrocycles held together by antiparallel CNCN dipolar interactions and CNH
      C(sp(2)) hydrogen bonding. Cyclic trimers and tetramers occur most frequently but
      everything from cyclic dimers to hexamers can be observed. Upon annealing of the
      samples at temperatures >150 degrees C, dimeric macrocyclic structures are
      observed, in which the two porphyrins are bridged by Cu atoms, originating from
      the surface, under formation of two CNCuNC coordination bonds. The trans-isomer
      builds up linear chains on Cu(111) at low coverage, whereas for higher coverage
      the molecules assemble in a periodic, densely packed structure. Both cis- and
      trans-bis(4'-cyanobiphenyl)-substituted Zn(II) porphyrins behave very differently
      on Cu(111) compared to similar porphyrins in literature on less reactive surfaces
      such as Au(111) and Ag(111). On the latter surfaces, there is no signal visible
      between molecular orientation and the crystal directions of the substrate,
      whereas on Cu(111), very strong adsorbate-substrate interactions have a
      dominating influence on all observed structures. This strong porphyrin-substrate
      interaction enables a much broader variety of structures, including also less
      favorable intermolecular bonding motifs and geometries.

PMID- 19760725
TI  - Red- and green-emitting iridium(III) complexes for a dual barometric and
      temperature-sensitive paint.
AB  - A new dual luminescent sensitive paint for barometric pressure and temperature
      (T) is presented. The green-emitting iridium(III) complex [Ir(ppy)(2)(carbac)]
      (ppy=2-phenylpyridine; carbac=1-(9H-carbazol-9-yl)-5,5-dimethylhexane-2,4-dione)
      was applied as a novel probe for T along with the red-emitting complex
      [Ir(btpy)(3)], (btpy=2-(benzo[b]thiophene-2-yl)pyridine) which functions as a
      barometric (in fact oxygen-sensitive) probe. Both iridium complexes were
      dissolved in different polymer materials to achieve optimal responses. The probe
      [Ir(ppy)(2)(carbac)] was dispersed in gas-blocking poly(acrylonitrile)
      microparticles in order to suppress any quenching of its luminescence by oxygen.
      The barometric probe [Ir(btpy)(3)], in turn, was incorporated in a cellulose
      acetate butyrate film which exhibits good permeability for oxygen. The effects of
      temperature on the response of the oxygen probe can be corrected by simultaneous
      optical determination of T, as the poly(acrylonitrile) microparticles containing
      the temperature indicator are incorporated into the film. The phosphorescent
      signals of the probes for T and barometric pressure, respectively, can be
      separated by optical filters due to the approximately 75 nm difference in their
      emission maxima. The dual sensor is applicable to luminescence lifetime imaging
      of T and barometric pressure. It is the first luminescent dual sensor material
      for barometric pressure/T based exclusively on the use of Ir(III) complexes in
      combination with luminescence lifetime imaging.

PMID- 19760726
TI  - Designed topology and site-selective metal composition in tetranuclear
      [MM'...M'M] linear complexes.
AB  - The ligand 1,3-bis[3-oxo-3-(2-hydroxyphenyl)propionyl]benzene (H(4)L), designed
      to align transition metals into tetranuclear linear molecules, reacts with M(II)
      salts (M=Ni, Co, Cu) to yield complexes with the expected [MMMM] topology. The
      novel complexes [Co(4)L(2)(py)(6)] (2; py=pyridine) and
      [Na(py)(2)][Cu(4)L(2)(py)(4)](ClO(4)) (3) have been crystallographically
      characterised. The metal sites in complexes 2 and 3, together with previously
      characterised [Ni(4)L(2)(py)(6)] (1), favour different coordination geometries.
      These have been exploited for the deliberate synthesis of the heterometallic
      complex [Cu(2)Ni(2)L(2)(py)(6)] (4). Complexes 1, 2, 3 and 4 exhibit
      antiferromagnetic interactions between pairs of metals within each cluster,
      leading to S=0 spin ground states, except for the latter cluster, which features
      two quasi-independent S=1/2 moieties within the molecule. Complex 4 gathers the
      structural and physical conditions, thus allowing it to be considered as
      prototype of a two-qbit quantum gate.

PMID- 19760727
TI  - Axially chiral facial amphiphiles with a dihydronaphthopentaphene structure as
      molecular tweezers for SWNTs.
AB  - Syntheses of chiral 6,15-dihydronaphtho[2,3-c]pentaphene derivatives of opposite
      configurations are reported. Starting from anthracene, the strategy involves two
      key steps: a Diels-Alder reaction on a prochiral dianthraquinone, and an
      enantiomeric resolution using (-)-menthol. The final molecules exhibit very
      strong optical activity, as shown by their circular dichroism spectra, and are
      examples of chiral facial amphiphiles. Their adsorption at the surface of single
      walled carbon nanotubes (SWNTs) has also been studied, and has been found to
      occur preferentially on 0.8-1.0 nm diameter nanotubes among the population of a
      high-pressure CO conversion (HiPco) SWNT sample (0.8-1.2 nm). The synthesised
      facial amphiphiles act as nano-tweezers for the diameter-selective solubilisation
      of SWNTs in water. The expected optical activities of the SWNT samples
      solubilised by each of the chiral amphiphiles have been studied by circular
      dichroism spectroscopy, but the results are not yet conclusive.

PMID- 19760728
TI  - Supramolecular architectures by fullerene-bridged bis(permethyl-beta
      cyclodextrin)s with porphyrins.
AB  - The Hirsch-Bingel reaction of bis{4-methyl[1,2,3]triazolyl}malonic ester-bridged
      bis(permethyl-beta-cyclodextrin) 1 with C(60) has led to the formation of a new
      fullerene-bridged bis(permethyl-beta-cyclodextrin) 2, which has been
      comprehensively characterized by NMR spectroscopy, MALDI-MS, and elemental
      analysis. Taking advantage of the high affinity between 2 and 5,10,15,20
      tetrakis(4-sulfonatophenyl)porphyrin (3) or [5,10,15,20-tetrakis(4
      sulfonatophenyl)porphinato]zinc(II) (4), linear supramolecular architectures with
      a width of about 2 nm and a length ranging from hundreds of nanometers to micron
      dimension were conveniently constructed and fully investigated by transmission
      electron microscopy (TEM), atomic force microscopy (AFM), and scanning electron
      microscopy (SEM). Significantly, the photoinduced electron-transfer (PET) process
      between porphyrin and C(60) moieties takes place within the 23 and 24
      supramolecular architectures under light irradiation, leading to the highly
      efficient quenching of the porphyrin fluorescence. The PET process and the charge
      separated state were investigated by means of fluorescence spectroscopy,
      fluorescence decay, cyclic voltammetry, and nanosecond transient absorption
      measurements.

PMID- 19760729
TI  - Fullerol-titania charge-transfer-mediated photocatalysis working under visible
      light.
AB  - The development of visible-light-active photocatalysts is being investigated
      through various approaches. In this study, C(60)-based sensitized photocatalysis
      that works through the charge transfer (CT) mechanism is proposed and tested as a
      new approach. By employing the water-soluble fullerol (C(60)(OH)(x)) instead of
      C(60), we demonstrate that the adsorbed fullerol activates TiO(2) under visible
      light irradiation through the "surface-complex CT" mechanism, which is largely
      absent in the C(60)/TiO(2) system. Although fullerene and its derivatives have
      often been utilized in TiO(2)-based photochemical conversion systems as an
      electron transfer relay, their successful photocatalytic application as a visible
      light sensitizer of TiO(2) is not well established. Fullerol/TiO(2) exhibits
      marked visible photocatalytic activity not only for the redox conversion of 4
      chlorophenol, I(-), and Cr(VI), but also for H(2) production. The photoelectrode
      of fullerol/TiO(2) also generates an enhanced anodic photocurrent under visible
      light as compared with the electrodes of bare TiO(2) and C(60)/TiO(2), which
      confirms that the visible-light-induced electron transfer from fullerol to TiO(2)
      is particularly enhanced. The surface complexation of fullerol/TiO(2) induced a
      visible absorption band around 400-500 nm, which was extinguished when the
      adsorption of fullerol was inhibited by fluorination of the surface of TiO(2).
      The transient absorption spectroscopic measurement gave an absorption spectrum
      ascribed to fullerol radical cations (fullerol(*+)) the generation of which
      should be accompanied by the proposed CT. The theoretical calculation regarding
      the absorption spectra for the (TiO(2) cluster+fullerol) model also confirmed the
      proposed CT, which involves excitation from HOMO (fullerol) to LUMO (TiO(2)
      cluster) as the origin of the visible-light absorption.

PMID- 19760730
TI  - Total synthesis of the bicyclic depsipeptide HDAC inhibitors spiruchostatins A
      and B, 5''-epi-spiruchostatin B, FK228 (FR901228) and preliminary evaluation of
      their biological activity.
AB  - The bicyclic depsipeptide histone deacetylase (HDAC) inhibitors spiruchostatins A
      and B, 5''-epi-spiruchostatin B and FK228 were efficiently synthesized in a
      convergent and unified manner. The synthetic method involved the following
      crucial steps: i) a Julia-Kocienski olefination of a 1,3-propanediol-derived
      sulfone and a L- or D-malic acid-derived aldehyde to access the most
      synthetically challenging unit, (3S or 3R,4E)-3-hydroxy-7-mercaptohept-4-enoic
      acid, present in a D-alanine- or D-valine-containing segment; ii) a condensation
      of a D-valine-D-cysteine- or D-allo-isoleucine-D-cysteine-containing segment with
      a D-alanine- or D-valine-containing segment to directly assemble the
      corresponding seco-acids; and iii) a macrocyclization of a seco-acid using the
      Shiina method or the Mitsunobu method to construct the requisite 15- or 16
      membered macrolactone. The present synthesis has established the C5''
      stereochemistry of spiruchostatin B. In addition, HDAC inhibitory assay and the
      cell-growth inhibition analysis of the synthesized depsipeptides determined the
      order of their potency and revealed some novel aspects of structure-activity
      relationships. It was also found that unnatural 5''-epi-spiruchostatin B shows
      extremely high selectivity (ca. 1600-fold) for class I HDAC1 (IC(50)=2.4 nM) over
      class II HDAC6 (IC(50)=3900 nM) with potent cell-growth-inhibitory activity at
      nanomolar levels of IC(50) values.

PMID- 19760731
TI  - Variations in the mechanisms of direct metallation of cyclic and acyclic aminals.

PMID- 19760732
TI  - Metallomacrocycles with a difference: macrocyclic complexes with exocyclic
      ruthenium(II)-containing domains.
AB  - The templated synthesis of organic macrocycles containing rings of up to 96 atoms
      and three 2,2'-bipyridine (bpy) units is described. Starting with the bpy-centred
      ligands 5,5'-bis[3-(1,4-dioxahept-6-enylphenyl)]-2,2'-bipyridine and 5,5'-bis[3
      (1,4,7-trioxadec-9-enylphenyl)]-2,2'-bipyridine, we have applied Grubbs'
      methodology to couple the terminal alkene units of the coordinated ligands in
      [FeL3]2+ complexes. Hydrogenation and demetallation of the iron(II)-containing
      macrocyclic complexes results in the isolation of large organic macrocycles. The
      latter bind {Ru(bpy)2} units to give macrocyclic complexes with exocyclic
      ruthenium(II)-containing domains. The complex [Ru(bpy)2(L)]2+ (isolated as the
      hexafluorophosphate salt), in which L=5,5'-bis[3-(1,4,7,10-tetraoxatridec-12
      enylphenyl)]-2,2'-bipyridine, undergoes intramolecular ring-closing metathesis to
      yield a macrocycle which retains the exocyclic {Ru(bpy)2} unit. The
      poly(ethyleneoxy) domains in the latter macrocycle readily scavenge sodium ions,
      as proven by single-crystal X-ray diffraction and atomic absorption spectroscopy
      data for the bulk sample. In addition to the new compounds, a series of model
      complexes have been fully characterized, and representative single-crystal X-ray
      structural data are presented for iron(II) and ruthenium(II) acyclic and
      macrocyclic species.

PMID- 19760733
TI  - Designing simple tridentate ligands for highly luminescent europium complexes.
AB  - A series of tridentate benzimidazole-substituted pyridine-2-carboxylic acids have
      been prepared with a halogen, methyl or alkoxy group in the 6-position of the
      benzimidazole ring, which additionally contains a solubilising N-alkyl chain. The
      ligands form neutral homoleptic nine-coordinate lanthanum, europium and terbium
      complexes as established from X-ray crystallographic analysis of eight
      structures. The coordination polyhedron around the lanthanide ion is close to a
      tricapped trigonal prism with ligands arranged in an up-up-down fashion. The
      coordinated ligands serve as light-harvesting chromophores in the complexes with
      absorption maxima in the range 321-341 nm (epsilon=(4.9-6.0)x10(4) M(-1) cm(-1))
      and triplet-state energies between 21 300 and 18 800 cm(-1); the largest
      redshifts occur for bromine and electron-donor alkoxy substituents. The ligands
      efficiently sensitise europium luminescence with overall quantum yields
      (Q(L)(Eu)) and observed lifetimes (tau(obs)) reaching 71 % and 3.00 ms,
      respectively, in the solid state and 52 % and 2.81 ms, respectively, in
      CH(2)Cl(2) at room temperature. The radiative lifetimes of the Eu((5)D(0)) level
      amount to tau(rad)=3.6-4.6 ms and the sensitisation efficiency
      eta(sens)=Q(L)(Eu)(tau(rad)/tau(obs)) is close to unity for most of the complexes
      in the solid state and equal to approximately 80 % in solution. The photophysical
      parameters of the complexes correlate with the triplet energy of the ligands,
      which in turn is determined by the nature of the benzimidazole substituent.
      Facile modification of the ligands makes them promising for the development of
      brightly emissive europium-containing materials.

PMID- 19760734
TI  - Efficient synthesis of cryptophycin-52 and novel para-alkoxymethyl unit A
      analogues.
AB  - Cryptophycins are a family of highly cytotoxic, cyclic depsipeptides. They
      display antitumour activity that is largely maintained for multi-drug-resistant
      tumour cells. Cryptophycins are composed of four building blocks (units A-D) that
      correspond to the respective amino and hydroxy acids. A new synthetic route to
      unit A allows the selective generation of all four stereogenic centres in a
      short, efficient and reliable synthesis and contributes to an easier and faster
      synthesis of cryptophycins. The first two stereogenic centres are introduced by a
      catalytic asymmetric dihydroxylation, whereas the remaining two stereogenic
      centres are introduced with substrate control of diastereoselectivity. The
      stereogenic diol function also serves as the epoxide precursor. The approach was
      used to synthesise the native unit A building block as well as three para
      alkoxymethyl analogues from which cryptophycin-52 and three analogous
      cryptophycins were prepared. Macrocyclisation of the seco-depsipeptides was based
      on ring-closing metathesis.

PMID- 19760735
TI  - Novel oxygenations with IBX.

PMID- 19760736
TI  - Trapping reactive metal-carbene complexes by a bis-pocket porphyrin: X-ray
      crystal structures of Ru=CHCO(2)Et and trans-[Ru(CHR)(CO)] species and highly
      selective carbenoid transfer reactions.

PMID- 19760737
TI  - Direct dehydrogenative amide synthesis from alcohols and amines catalyzed by
      gamma-alumina supported silver cluster.

PMID- 19760738
TI  - Iodine(V)/ruthenium(III)-cocatalyzed oxidations: a highly efficient tandem
      catalytic system for the oxidation of alcohols and hydrocarbons with oxone.

PMID- 19760739
TI  - Effects of developmental age, brain region, and time in culture on long-term
      proliferation and multipotency of neural stem cell populations.
AB  - Neural stem cells (NSCs) in the murine subventricular zone (SVZ) niche allow life
      long neurogenesis. During the first postnatal month and throughout aging, the
      decrease of neuroblasts and the rise of astrocytes results in diminished
      neurogenesis and increased astrocyte:neuron ratio. Also, a different neurogenic
      activity characterizes the SVZ periventricular region (LV, lateral ventricle) as
      compared to its rostral extension (RE). In order to investigate whether and to
      what extent these physiological modifications may be ascribed to intrinsic
      changes of the endogenous NSC/progenitor features, we performed a functional
      analysis on NSCs isolated and cultured from LV and RE tissues at distinct
      postnatal stages that are marked by striking modifications to the SVZ niche in
      vivo. We evaluated the effect of age and brain region on long-term proliferation
      and multipotency, and characterized the cell type composition of NSC-derived
      progeny, comparing this make-up to that of region- and age-matched primary neural
      cultures. Furthermore, we analyzed the effect of prolonged in vitro expansion on
      NSC functional properties. We documented age- and region-dependent differences on
      the clonogenic efficiency and on the long-term proliferative capacity of NSCs.
      Also, we found age- and region-dependent quantitative changes in the cell
      composition of NSC progeny (decreased quantity of neurons and oligodendrocytes;
      increased amount of astroglial cells) and these differences were maintained in
      long-term cultured NSC populations. Overall, these data strengthen the hypothesis
      that age- and region-dependent differences in neurogenesis (observed in vivo) may
      be ascribed to the changes in the intrinsic developmental program of the NSC
      populations.

PMID- 19760740
TI  - Afferent and efferent projections of the central caudal nidopallium in the pigeon
      (Columba livia).
AB  - The central caudal nidopallium (NCC) is a large subdivision of the nidopallium in
      the pigeon brain, but its connectional anatomy is unknown. Here, we examined the
      connections of NCC by using tract-tracing methods. Injections of cholera toxin B
      chain (CTB) in NCC labeled many neurons within NCC. Outside NCC, many labeled
      neurons were found in the dorsal intermediate mesopallium and medialmost part of
      the medial intermediate nidopallium, with a few in the intermediate (AI) and
      medial (AM) arcopallium. In the thalamus, labeled neurons were located in the
      subrotundal nucleus, the shell region of nucleus ovoidalis, and the caudal part
      of the dorsolateral posterior thalamic nucleus. Injections of biotinylated
      dextran amine (BDA) in NCC labeled many fibers running rostrocaudally within NCC.
      Some of these terminated in the dorsal intermediate mesopallium, but the size of
      the terminal field was smaller than the region of the dorsal intermediate
      mesopallium that provided the projection to NCC. NCC sent numerous efferents to
      AI and AM but few to the thalamus. In contrast, after CTB injections in the
      dorsal intermediate mesopallium, a few neurons were labeled in NCC, but, after
      BDA injections in the dorsal intermediate mesopallium, large numbers of labeled
      fibers were seen to project widely throughout NCC. These findings indicate that
      the flow of information is predominantly from the dorsal intermediate mesopallium
      to NCC and from there to the arcopallium (AI and AM). The arcopallial outflow to
      the medial hypothalamus could imply that NCC is involved in neuroendocrine and
      autonomic functions and is limbic in nature.

PMID- 19760741
TI  - Social relations and PTSD symptoms: a prospective study on earthquake-impacted
      adolescents in Taiwan.
AB  - This prospective longitudinal study examined two competing models, a traditional
      social support model and a supportive and detrimental social relations model, to
      clarify the association of PTSD symptoms with supportive and detrimental social
      relations. Seven-hundred five adolescents living near the epicenter of the Taiwan
      Chi-Chi Earthquake participated in the study. The models were evaluated and cross
      validated using structural equation modeling. The supportive and detrimental
      social relations model appeared to be a better fit. After further evaluation of
      three nested versions of the supportive and detrimental social relations model,
      detrimental social relations was found to partially mediate the relationship
      between PTSD symptoms 1 and 2 years following the earthquake. The findings
      suggest that helping adolescents deal with detrimental social relations can
      contribute to postdisaster adjustment.

PMID- 19760742
TI  - Therapist empathy and client anxiety reduction in motivational interviewing: "She
      carries with me, the experience".
AB  - In this article, we examine the use of motivational interviewing (MI) to treat
      generalized anxiety disorder (GAD) by means of case illustration that focuses on
      four categories drawn from the client's experience of the key ingredients in MI
      therapy. The case illustration, drawn from the York study on combining MI and
      cognitive behavior therapy in the treatment of GAD (uses the client's pre- and
      post-therapy narrative interviews) to arrive at categories representative of the
      client's experience of MI therapy. The results of the qualitative analysis
      highlight the key contributions to positive client outcomes and readiness for
      change in brief MI therapy for GAD.

PMID- 19760743
TI  - Beyond behavior: eliciting broader change with motivational interviewing.
AB  - Descriptions of Motivational interviewing (MI) usually focus on helping clients
      change a single problematic behavior. In contrast, the current case study shows
      that MI can serve as a more comprehensive psychotherapy, focused not only on
      multiple problem behaviors but also on broader change consistent with its roots
      in client-centered therapy. In this case, the therapist interwove a focus on
      several discrete behaviors with a focus on broader lifestyle change as well as
      increased clarity of client cognitions, values, and choices, resulting in several
      lasting changes.

PMID- 19760744
TI  - Exploration of chromatic aberration for multiplanar imaging: proof of concept
      with implications for fast, efficient autofocus.
AB  - Image-based autofocus determines focus directly from the specimen (as opposed to
      reflective surface positioning with an offset), but sequential acquisition of a
      stack of images to measure resolution/sharpness and find best focus is slower
      than reflective positioning. Simultaneous imaging of multiple focal planes, which
      is also useful for 3D imaging of live cells, is faster but requires complicated
      optics. With color CCD cameras and white light sources commonly available, we
      asked if axial chromatic aberration can be utilized to acquire multiple focal
      planes simultaneously, and if it can be controlled through a range sufficient for
      practical use. For proof of concept, we theoretically and experimentally explored
      the focal differences between three narrow wavelength bands on a 3-chip color CCD
      camera with and without glass inserts of various thicknesses and dispersions. Ray
      tracing yielded changes in foci of 0.65-0.9 microm upon insertion of 12.5-mm
      thick glass samples for green (G, 522 nm) vs. blue (B, 462 nm) and green vs. red
      (G-R, 604 nm). On a microscope: (1) With no glass inserts, the differences in
      foci were 2.15 microm (G-B) and 0.43 microm (G-R); (2) With glass inserts, the
      maximum change in foci for G vs. B was 0.44 microm and for G vs. R was 0.26
      microm; and (3) An 11.3 mm thick N-BK7 glass insert shifted the foci 0.9 microm
      (R), 0.6 microm (G), and 0.35 microm (B), such that the B and R foci were farther
      apart (2.1 microm vs. 1.7 microm) and the R and G foci were closer together (0.25
      microm vs. 0.45 microm). The slopes of the differences in foci were dependent on
      thickness, index of refraction, and dispersion. The measured differences in foci
      are comparable to the axial steps of 0.1-0.24 microm commonly used for autofocus,
      and focal plane separation can be altered by inserting optical elements of
      various dispersions and thicknesses. By enabling acquisition of multiple, axially
      offset images simultaneously, chromatic aberration, normally an imaging pariah,
      creates a possible mechanism for efficient multiplanar imaging of multiple
      spectral bands from white light illumination.

PMID- 19760745
TI  - Motivational interviewing in the assessment and management of suicidality.
AB  - Motivational Interviewing (MI) can be effectively applied to clinical crises and
      suicidal patients. A case example of a suicidal patient demonstrates traditional
      management combined with two evidence-based practices: MI and Collaborative
      Assessment and Management of Suicidality. The case example illustrates some
      benefits and limitations of the application of these innovative approaches in a
      difficult area of clinical practice. A rationale for further clinical use is
      advanced.

PMID- 19760746
TI  - Robust signal detection in 3D fluorescence microscopy.
AB  - Robust detection and localization of biomolecules inside cells is of great
      importance to better understand the functions related to them. Fluorescence
      microscopy and specific staining methods make biomolecules appear as point-like
      signals on image data, often acquired in 3D. Visual detection of such point-like
      signals can be time consuming and problematic if the 3D images are large,
      containing many, sometimes overlapping, signals. This sets a demand for robust
      automated methods for accurate detection of signals in 3D fluorescence
      microscopy. We propose a new 3D point-source signal detection method that is
      based on Fourier series. The method consists of two parts, a detector, which is a
      cosine filter to enhance the point-like signals, and a verifier, which is a sine
      filter to validate the result from the detector. Compared to conventional
      methods, our method shows better robustness to noise and good ability to resolve
      signals that are spatially close. Tests on image data show that the method has
      equivalent accuracy in signal detection in comparison to visual detection by
      experts. The proposed method can be used as an efficient point-like signal
      detection tool for various types of biological 3D image data.

PMID- 19760747
TI  - Exon skipping-mediated dystrophin reading frame restoration for small mutations.
AB  - Exon skipping using antisense oligonucleotides (AONs) has successfully been used
      to reframe the mRNA in various Duchenne muscular dystrophy patients carrying
      deletions in the DMD gene. In this study we tested the feasibility of the exon
      skipping approach for patients with small mutations in in-frame exons. We first
      identified 54 disease-causing point mutations. We selected five patients with
      nonsense or frameshifting mutations in exons 10, 16, 26, 33, and 34. Wild-type
      and mutation specific 2'OMePS AONs were tested in cell-free splicing assays and
      in cultured cells derived from the selected patients. The obtained results
      confirm cell-free splicing assay as an alternative system to test exon skipping
      propensity when patients' cells are unavailable. In myogenic cells, similar
      levels of exon skipping were observed for wild-type and mutation specific AONs
      for exons 16, 26, and 33, whereas for exon 10 and exon 34 the efficacy of the
      AONs was significantly different. Interestingly, in some cases skipping
      efficiencies for mutated exons were quite dissimilar when compared with previous
      reports on the respective wild-type exons. This behavior may be related to the
      effect of the mutations on exon skipping propensity, and highlights the
      complexity of identifying optimal AONs for skipping exons with small mutations.

PMID- 19760748
TI  - Genetic and cellular studies of oxidative stress in methylmalonic aciduria (MMA)
      cobalamin deficiency type C (cblC) with homocystinuria (MMACHC).
AB  - Methylmalonic aciduria (MMA) cobalamin deficiency type C (cblC) with
      homocystinuria (MMACHC) is the most frequent genetic disorder of vitamin B(12)
      metabolism. The aim of this work was to identify the mutational spectrum in a
      cohort of cblC-affected patients and the analysis of the cellular oxidative
      stress and apoptosis processes, in the presence or absence of vitamin B(12). The
      mutational spectrum includes nine previously described mutations: c.3G>A (p.M1L),
      c.217C>T (p.R73X), c.271dupA (p.R91KfsX14), c.331C>T (p.R111X), c.394C>T
      (p.R132X), c.457C>T (p.R153X), c.481C>T (p.R161X), c.565C>A (p.R189S), and
      c.615C>G (p.Y205X), and two novel changes, c.90G>A (p.W30X) and c.81+2T>G
      (IVS1+2T>G). The most frequent change was the known c.271dupA mutation, which
      accounts for 85% of the mutant alleles characterized in this cohort of patients.
      Owing to its high frequency, a real-time PCR and subsequent high-resolution
      melting (HRM) analysis for this mutation has been established for diagnostic
      purposes. All cell lines studied presented a significant increase of
      intracellular reactive oxygen species (ROS) content, and also a high rate of
      apoptosis, suggesting that elevated ROS levels might induce apoptosis in cblC
      patients. In addition, ROS levels decreased in hydroxocobalamin-incubated cells,
      indicating that cobalamin might either directly or indirectly act as a scavenger
      of ROS. ROS production might be considered as a phenotypic modifier in cblC
      patients, and cobalamin supplementation or additional antioxidant drugs might
      suppress apoptosis and prevent cellular damage in these patients.

PMID- 19760749
TI  - Defining the pathogenic role of telomerase mutations in myelodysplastic syndrome
      and acute myeloid leukemia.
AB  - The primary pathology in many cases of myelodysplasia (MDS) and acute myeloid
      leukemia (AML) remains unknown. In some cases, two or more affected members have
      been identified in the same family. To date, mutations in two genes have been
      directly implicated: the hematopoietic transcription factors RUNX1 (runt-related
      transcription factor 1) and CEBPA (CCATT-box enhancer binding protein alpha).
      However, there are also other familial cases of MDS/AML where the genetic basis
      remains unknown. Both MDS, and to a lesser extent AML, have been observed in
      cases of the bone marrow failure syndrome dyskeratosis congenita, in which
      telomerase mutations have been identified. Recently, an increased incidence of
      telomerase reverse transcriptase mutations has been reported in a series of de
      novo AML. We have now identified novel mutations in the telomerase RNA (TERC) or
      telomerase reverse transcriptase component (TERT) within 4 of 20 families
      presenting with familial MDS/AML. Functional analysis has demonstrated that all
      mutations adversely impact on telomerase activity in vitro, and affected
      individuals have short telomeres. These families, in conjunction with a review of
      previously published cases, help to further define the pathological role of
      telomerase mutations in MDS/AML and have implications for the biology, treatment
      and screening regimen of de novo cases.

PMID- 19760750
TI  - Two-round coamplification at lower denaturation temperature-PCR (COLD-PCR)-based
      sanger sequencing identifies a novel spectrum of low-level mutations in lung
      adenocarcinoma.
AB  - Reliable identification of cancer-related mutations in TP53 is often problematic,
      as these mutations can be randomly distributed throughout numerous codons and
      their relative abundance in clinical samples can fall below the sensitivity
      limits of conventional sequencing. To ensure the highest sensitivity in mutation
      detection, we adapted the recently described coamplification at lower
      denaturation temperature-PCR (COLD-PCR) method to employ two consecutive rounds
      of COLD-PCR followed by Sanger sequencing. Using this highly sensitive approach
      we screened 48 nonmicrodissected lung adenocarcinoma samples for TP53 mutations.
      Twenty-four missense/frameshift TP53 mutations throughout exons 5 to 8 were
      identified in 23 out of 48 (48%) lung adenocarcinoma samples examined, including
      eight low-level mutations at an abundance of approximately 1 to 17%, most of
      which would have been missed using conventional methodologies. The identified
      alterations include two rare lung adenocarcinoma mutations, one of which is a
      "disruptive" mutation currently undocumented in the lung cancer mutation
      databases. A sample harboring a low-level mutation ( approximately 2% abundance)
      concurrently with a clonal mutation (80% abundance) revealed intratumoral TP53
      mutation heterogeneity. The ability to identify and sequence low-level mutations
      in the absence of elaborate microdissection, via COLD-PCR-based Sanger
      sequencing, provides a platform for accurate mutation profiling in clinical
      specimens and the use of TP53 as a prognostic/predictive biomarker, evaluation of
      cancer risk, recurrence, and further understanding of cancer biology.

PMID- 19760751
TI  - Novel missense mutations in the FOXC2 gene alter transcriptional activity.
AB  - Mutations in the FOXC2 gene that codes for a forkhead transcription factor are
      associated with primary lymphedema that usually develops around puberty.
      Associated abnormalities include distichiasis and, very frequently, superficial
      and deep venous insufficiency. Most mutations reported so far either truncate the
      protein or are missense mutations in the forkhead domain causing a loss of
      function. The haplo-insufficient state is associated with lymphatic hyperplasia
      in mice as well as in humans. We analyzed the FOXC2 gene in 288 patients with
      primary lymphedema and found 11 pathogenic mutations, of which 9 are novel. Of
      those, 5 were novel missense mutations of which 4 were located outside of the
      forkhead domain. To examine their pathogenic potential we performed a
      transactivation assay using a luciferase reporter construct driven by FOXC1
      response elements. We found that the mutations outside the forkhead domain cause
      a gain of function as measured by luciferase activity. Patient characteristics
      conform to previous reports with the exception of distichiasis, which was found
      in only 2 patients out of 11. FOXC2 mutations causing lymphedema-distichiasis
      syndrome reported thus far result in haplo-insufficiency and lead to lymphatic
      hyperplasia. Our results suggest that gain-of-function mutations may also cause
      lymphedema. One would expect that in this case, lymphatic hypoplasia would be the
      underlying abnormality. Patients with activating mutations might present with
      Meige disease.

PMID- 19760752
TI  - ssSNPTarget: genome-wide splice-site Single Nucleotide Polymorphism database.
AB  - Deep sequencing has shown that over 90% of human genes undergo alternative
      splicing. The splicing process requires exon-intron boundary recognition. SNPs
      located in the boundaries (splice sites) influence exon configuration. Also,
      splice site SNPs (ssSNPs) alter translation efficiency of the mRNA and lead to
      important changes in disease susceptibility. We developed the ssSNPTarget
      database to provide ssSNPs on human and mouse genes. It includes: 1) ssSNP
      distribution information in human and mouse genes; 2) effects of SNPs in splice
      sites: junction strength change, protein domain change, and alternative splicing
      events (exon skipping, 5'- or 3'-exon extension); 3) splice site conservation in
      eukaryotes; and 4) associated disease information derived from OMIM, GAD, and
      HGMD. ssSNPTarget contains 1,576 human ssSNPs associated with 1,193 genes and 538
      mouse ssSNPs associated with 281 genes. Users can query ssSNPTarget with several
      types of search terms (gene symbol, SNP rs number, transcript ID, or genomic
      position), and the information can be accessed at
      http://variome.kobic.re.kr/ssSNPTarget/ or http://ssSNPTarget.org.

PMID- 19760753
TI  - Iron depletion before HCV antiviral therapy: a pilot, randomized, controlled
      trial.
AB  - It is not known whether iron depletion before pegylated IFN or combination
      treatment improves sustained virological response (SVR) rate in patients with
      chronic hepatitis C, despite its use in clinical practice in this setting. We
      aimed to investigate whether blood letting improves the efficacy (SVR) and
      tolerability of PEG-IFNalpha2b + Ribavirin in chronic hepatitis C patients.
      Patients with chronic hepatitis C and ferritin >100 ng/mL were randomized to: (1)
      repeated phlebotomies to obtain a ferritin level <50 ng/mL followed by pegylated
      Interferon alpha2b + ribavirin (active arm); or (2) pegylated-Interferon alpha2b
      + ribavirin (control arm). Primary endpoint was SVR rate, secondary endpoint was
      frequency of clinical and laboratory grade 3-4 adverse events. Thirty-three
      patients were enrolled in the study (19 in active arm, 14 in control arm). The 19
      patients in the active arm underwent a median of 5 phlebotomies (range: 1-9) to
      achieve the targeted ferritin (<50 ng/mL). Phlebotomies significantly reduced
      ferritin, iron, transferrin saturation, aspartate aminotransferase, alanine
      aminotransferase, and hemoglobin levels. Platelet count significantly increased,
      whereas HCV-RNA levels remained unchanged. After antiviral therapy overall SVR
      was 31.6% in active arm and 21.4% in control arm (P = 0.698). Considering only
      the 18 patients who were naive to antiviral therapy, SVR was 60% in active arm
      versus 25% in control arm (P = 0.188). Tolerability, drug dose reduction or
      withdrawal were similar in the two arms. In conclusion phlebotomies do not
      increase the overall efficacy of antiviral therapy. However, the strong trend to
      higher SVR in naive patients undergoing phlebotomies warrants further
      investigation.

PMID- 19760754
TI  - Analysis of 39 Crohn's disease risk loci in Swedish inflammatory bowel disease
      patients.

PMID- 19760755
TI  - Cadaveric study of nerves supplying the membranous urethra.
AB  - AIMS: To better understand the anatomy of the region of the male membranous
      urethra in order to preserve continence during radical cystectomy and
      prostatectomy. METHODS: Cadaveric dissections of 15 male specimens were
      undertaken to investigate the nerves to membranous urethra. The nerves were
      traced from both an intrapelvic approach and a perineal approach. The origin,
      course, and distribution of the branches to the membranous urethra region were
      investigated in detail. RESULTS: The membranous urethra is innervated by branches
      of inferior hypogastric plexus (IHP) and intrapelvic and extrapelvic branches of
      pudendal nerve (PN). The pelvic nerve from IHP originated from the caudal most
      root of the pelvic splanchnic nerve, running along the surface of the levator ani
      muscle (LAM) to enter the membranous urethra at the 5 and 7 O'clock positions. In
      40% of specimens we found that the intrapelvic branches were supplied by the PN.
      Before exiting the pudendal canal, PN gives off an intrapelvic branch that
      traverses the LAM to course with the pelvic nerve and innervate the membranous
      urethra; the distance between these intrapelvic branches and prostatic apex is
      5.3 +/- 1.8 mm. The branches originating from the dorsal nerve of penis innervate
      the membranous urethra in 53.3% of specimens; these nerve branches are located
      4.2 +/- 1.1 mm from the prostatic apex. CONCLUSIONS: Dissection of the seminal
      vesicles and the prostatic apex during radical cystectomy and prostatectomy
      likely injures the nerve responsible for continence.

PMID- 19760756
TI  - Aging and the underactive detrusor: a failure of activity or activation?
AB  - AIMS: To examine the known and potential contributions of motor, sensory, and
      biomechanical dysfunctions to the clinical problems of detrusor underactivity and
      detrusor hyperactivity/impaired contractility. METHODS: A review of the current
      literature on non-obstructive voiding dysfunction associated with aging was
      conducted. The functional impact of age-induced biomechanical tissue change via
      alterations in sensory transduction is considered. RESULTS: Impaired
      contractility has been regarded as etiologic of detrusor underactivity. However,
      an age-related degradation in detrusor contractility as the primary contributor
      to impaired bladder emptying has not been conclusively demonstrated. To the
      extent that detrusor contraction force and duration are dependent upon efferent
      nerve activity and thus reflex responses to sensory activity, there is a
      potential impact of impaired sensory function on voiding efficiency. Structural
      and functional tissue changes accompanying aging may result in altered bladder
      afferent function, with subsequent reflex impairment of detrusor voiding
      function. CONCLUSIONS: The relative contributions of motor, sensory, and
      biomechanical dysfunctions to impaired voiding performance independent of outlet
      obstruction associated with aging remain to be elucidated.

PMID- 19760757
TI  - Sacral neuromodulation in diabetic patients: success and complications in the
      treatment of voiding dysfunction.
AB  - AIMS: We compared success rates, subsequent complications, and possible
      indications for success of sacral neuromodulation (SNM) for urinary voiding
      dysfunction in diabetic and non-diabetic patients. METHODS: Thirty-two diabetic
      patients (mean age 61.8 years, range 27-83) with urge incontinence, urgency
      frequency syndrome, and/or urinary retention refractory to non-surgical treatment
      were retrospectively evaluated along with 211 non-diabetic patients (mean age
      54.1 years, range 20-86) with similar symptoms. All patients who experienced
      >or=50% reduction in urinary symptoms following a 7- to 21-day test period went
      on to permanent SNM device implantation. RESULTS: No significant difference was
      found with respect to successful conversion rates from the test period to
      permanent implantation between diabetic and non-diabetic patients. Long-term
      success rates at a mean followup of 29.3 months following permanent device
      implantation for diabetic patients were 69.2% of those with urge incontinence,
      85.7% of those with urgency-frequency, and 66.7% of those with urinary retention.
      The non-diabetic cohort had success rates of 67.0% for urge incontinence, 67.8%
      for urgency/frequency, and 58.2% for urinary retention (P = 0.823, 0.157, and
      0.631, respectively). No patient experienced intraoperative complications. Nine
      of 24 (37.5%) devices were explanted postoperatively in diabetic patients
      compared with 36 of 141 (25.5%) in non-diabetic patients (P = 0.224). The number
      of explants due to infection was higher in diabetic patients (16.7%) versus non
      diabetic patients (4.3%; P = 0.018). CONCLUSIONS: No difference in long-term
      success rates was seen in diabetic patients when compared with similar, non
      diabetic patients. Diabetic patients did, however, have a higher incidence of
      device explantation due to infection.

PMID- 19760758
TI  - Zolpidem increases bladder capacity and decreases urine excretion in rats.
AB  - AIMS: To clarify the effects of zolpidem, a gamma-aminobutyric acid (GABA)(A)
      receptor agonist, on bladder function, and urine production, we investigated the
      effects of zolpidem administration on bladder overactivity induced by cerebral
      infarction (CI) and on urine excretion increased by water overloading in Wistar
      rats. METHODS: CI was induced by left middle cerebral artery occlusion. The
      effects on bladder function of zolpidem alone or in combination with the GABA(A)
      receptor antagonist bicuculline, were then examined in the CI rats using
      cystometry. The antidiuretic effect of zolpidem was investigated in water-loaded
      and Brattleboro rats (genetically vasopressin-deficient). Blood samples were
      collected from water-loaded rats to determine the aldosterone level 1 and 6 hr
      after zolpidem administration. RESULTS: Zolpidem increased bladder capacity dose
      dependently, but had no significant effect on bladder contraction pressure in CI
      rats. Bicuculline dose-dependently inhibited zolpidem-induced increases in
      bladder capacity without affecting bladder contraction pressure. Zolpidem dose
      dependently decreased the volume of urine excreted in water-loaded and
      Brattleboro rats. Compared with the control group, zolpidem significantly
      increased the aldosterone concentration in the plasma of water-loaded rats 1 hr
      after administration. CONCLUSIONS: Zolpidem increased bladder capacity via a
      GABAergic mechanism in CI rats, and suppressed urine excretion via a pathway that
      was not through activation of vasopressin V(2) receptors in water-loaded and
      Brattleboro rats. These results suggest that zolpidem may improve nocturia via an
      increase in bladder capacity and a decrease in urine excretion.

PMID- 19760759
TI  - Urine production and bladder diary measurements in women with type 2 diabetes
      mellitus and their relation to lower urinary tract symptoms and voiding
      dysfunction.
AB  - AIMS: To establish bladder diary measurements in women with type 2 diabetes
      mellitus (DM) and their relation to bothersome LUTS and voiding dysfunction.
      METHODS: One hundred ten women with type 2 DM were assessed using the King's
      Health and ICIQ-FLUTS questionnaires. Patients were divided into bothersome and
      non-bothersome LUTS according to bother scale of the ICIQ-FLUTS. Voiding was
      assessed with free flow rate and residuals. Three day bladder diary measurements
      were obtained and 24 hr, daytime and nighttime urine production, daytime
      frequency, nighttime frequency, maximum bladder capacity, mean voided volume,
      mean daytime and nighttime voided volumes, and incontinence episodes were
      recorded. Differences in bladder diary measurements between bothersome and non
      bothersome groups and between normal and abnormal voiding groups were established
      with multivariate analysis. Correlations between urine production and voided
      volumes and between diary measurements and domains of the ICIQ-FLUTS were
      established. RESULTS: There were no differences in urine production, between
      bothersome and non-bothersome LUTS groups. Women with bothersome LUTS had greater
      nighttime frequency (2.6 vs. 1.4) and number of incontinence episodes (3.3 vs.
      0.4). Abnormal voiding group had higher nocturnal urine production (1,007 ml vs.
      654 ml). There were significant correlations between nighttime frequency, number
      of incontinence episodes, and the storage and incontinence domains of the ICIQ
      FLUTS. Bladder capacity significantly increased with increased total urine
      volumes. CONCLUSIONS: Bothersome LUTS in DM is not associated with increased
      urine production. Bladder capacity increased with total urine volume. Nocturia
      and incontinence episodes were significantly associated with bothersome LUTS.

PMID- 19760761
TI  - Utility of fine-needle aspiration as a diagnostic technique in breast lumps.
AB  - Fine-needle aspiration cytology (FNAC) is a simple, accurate, and safe procedure
      for the diagnosis of palpable breast lumps. The purpose of this study is to
      emphasis the utilization of FNAC in the Sudan and to evaluate our experience to
      identify the types of various breast lesions. A one year descriptive longitudinal
      study was conducted in Khartoum, Sudan. We obtained information (patient's
      personal data) and Fine-Needle Aspiration (FNA) samples, for 200 patients with
      palpable breast lesions. Subsequent tissue biopsies were taken from 131 patients
      of the 200 studied patients. Data were analyzed using a computer's SPSS program.
      Pearson chi-square test was used for statistical analyses. The diagnoses of the
      200 breast FNAs were as follows: 61 (30.5%) were malignant, 5 (2.5%) were
      suspicious, and 134 (67%) were benign lesions. Subsequent histopathological
      examination was performed on 61 (100%) patients with malignant lesions, 5 (100%)
      of suspicious, and 65 (48.5%) patients of 134 patients with benign lesions. FNAC
      revealed a 92.6% sensitivity, a 95.2% specificity, a 95.5% positive predictive
      value, and a 92.2% negative predictive value. Of the 65 benign cases on cytology,
      five cases were found malignant on histopathology. FNAC of breast lesions is
      sensitive, specific, and highly accurate as the initial investigation of palpable
      breast lesions in a population of low resources and without screening program to
      diagnose breast cancer. We consequently encourage clinicians to embrace this
      procedure in the management of patients.

PMID- 19760760
TI  - A cross-sectional study of ultrasound estimated bladder weight in a sample of men
      and women without lower urinary tract symptoms.
AB  - AIMS: A non-invasive ultrasound method of estimating bladder weight (UEBW) has
      been proposed as diagnostic for outflow tract obstruction and detrusor
      overactivity in men and women. There are no data on asymptomatic men and women.
      This study aimed to examine the relationship between UEBW, age, height, body mass
      index (BMI), and body surface area (BSA). METHODS: Healthy volunteers of either
      sex were recruited from hospital staff, visitors, and patients. All were screened
      as asymptomatic using a validated tool and variables recorded. Bladder scans were
      performed using the Bladderscan BVM 6500 (Verathon, Aylesbury, England). RESULTS:
      Thirty men and 40 women were included in the study. There was no correlation
      between UEBW and BMI or age. There was a statistically significant correlation
      between height and UEBW (r(s) = 0.78 (95% CI 0.66-0.86), P < 0.0001), span and
      UEBW (M,r(s) = 0.68, P < 0.0001, F,r(s) = 0.36, P < 0.02), BSA and UEBW (M,r(s) =
      0.75, P < 0.0001, F,r(s) = 0.34, P < 0.035), and height and UEBW (r(s) = 0.78
      (95% CI 0.66-0.86), P < 0.0001) for both men and women. CONCLUSIONS: This study
      has described a highly significant association between UEBW and height, and span
      and BSA in a group of asymptomatic individuals of both sexes. Caution should be
      taken when ascribing pathological significance to observations made in the
      absence of understanding of normal physiology.

PMID- 19760762
TI  - ASC/SIL ratio for cytotechnologists: A survey of its utility in clinical
      practice.
AB  - The atypical squamous cell to squamous intraepithelial lesion (ASC/SIL) ratio for
      cytotechnologists (CTs) may correlate with screening sensitivity in some
      laboratory settings. Whether this ratio can be applied to other laboratory
      settings is not known. We conducted a survey of nine cytology laboratories and
      correlated the ASC/SIL ratio of individual CTs with other laboratory
      characteristics. The ASC/SIL ratio for individual CTs varied from 0.6 to 4.5
      (mean: 1.9, median: 1.5). The ASC/SIL ratio within individual laboratories varied
      up to 567%; 25/78 (32%) CTs had an ASC/SIL ratio of less than 1.5, though only
      three of nine laboratories had more than one CT with a ratio this low.
      Laboratories that used 100% location guided screening (ThinPrep Imaging System)
      were much less likely to have a CT with a ratio <1.5 (1/20, 5%) than laboratories
      that never used location guided screening (14/34, 42%; P = 0.004). In addition,
      the normalized variance of these same laboratories that used location guided
      screening was significantly lower than those that did not (normalized standard
      deviation 0.32 vs. 0.55, P = 0.004). The ASC/SIL ratios did not correlate with
      laboratory volume, individual workload, or type of specimen preparation
      (conventional vs. liquid based). The ASC/SIL ratio for CTs varies widely between
      and within laboratories, and may correlate with the use of location guided
      screening. Very low ASC/SIL ratios are unusual, and CTs with low ratios may
      warrant further evaluation.

PMID- 19760763
TI  - CD13+ anaplastic large cell lymphoma with leukemic presentation and additional
      chromosomal abnormality.
AB  - Anaplastic large cell lymphoma (ALCL) is a highly malignant neoplasm
      characterized by pleomorphic appearance, different immunophenotypes and variable
      sites of involvement. Expression of myeloid-associated markers in anaplastic
      large cell lymphomas may mislead the medical team and result in delay of
      diagnosis due to unusual phenotype. It is important to diagnose this type of
      tumors and distinguish it from myeloid neoplasms (extramedullary myeloid cell
      tumors and histiocytic tumors) since therapy and prognosis are significantly
      different.A 16-year-old female patient presented with fever, lymphadenopathy, and
      high white blood cell count. Diagnosing a CD13+ ALCL with leukemic presentation
      with additional cytogenetic abnormality (duplication 5q35) was a significant
      diagnostic challenge.This combination of features, unusual for lymphoma, should
      be considered in differential diagnosis of myeloid neoplasms and fatal
      infections.

PMID- 19760764
TI  - Cytomorphologic features of primary anaplastic large cell lymphoma of the psoas
      muscle: a case report and literature review.
AB  - Ki-1 (CD30) positive anaplastic large cell lymphoma (ALCL) is an uncommon
      malignancy, which may present with nodal as well as extra-nodal disease. Primary
      skeletal muscle Ki-1 (CD30) positive ALCL is an even rarer event with few cases
      reported in the literature and only some with published cytomorphologic features.
      An 83-year-old woman underwent a fine needle aspiration (FNA) of a psoas muscle
      mass. Smears demonstrated a predominantly discohesive population of large
      pleomorphic cells. The nuclei were hypechromatic and lobulated, with often
      multinucleation. Nucleoli were prominent in a subset of cells. Cytoplasmic
      vacuolization was also present. No lymphoglandular bodies were identified. A
      cytodiagnosis of malignant cells favoring metastatic melanoma vs. poorly
      differentiated carcinoma was rendered. Morphologic and immunohistochemical
      features later revealed a primary psoas muscle Ki-1 (CD30) positive ALCL with
      negative staining for anaplastic large cell lymphoma kinase (ALK). Cytologic
      features of ALCL mimic epithelial neoplasms, sarcomas, melanoma and other
      lymphomas. Although rare, ALCL should be a diagnostic consideration when
      discohesive pleomorphic malignant cells are encountered on FNA of a muscle
      neoplasm.

PMID- 19760765
TI  - Cytologic features of adult spindle cell variant of rhabdomyosarcoma: a report of
      two cases.

PMID- 19760766
TI  - Restrictions in daily life after retinoblastoma from the perspective of the
      survivors.
AB  - BACKGROUND: Little is known about the impact of retinoblastoma (RB) on the health
      status of survivors in terms of disabilities and worries, both of which may
      restrict participation in activities of daily life. METHODS: In this population
      based cross-sectional study, content analysis was used to extract data on
      perceived restrictions and worries, from semi-structured interviews held with 156
      RB survivors aged 8-35 years. The International Classification of Functioning
      Disabilities and Health (ICF) was used as a framework. RESULTS: Of all survivors,
      55% perceive RB-related restrictions in daily life activities (school,
      professional career, mobility, self-care, intimate relationships).
      Young/adolescent survivors (6%) and adult survivors (15%) frequently report
      anxiety about developing a second primary tumor (SPT). Compared with the general
      population, RB survivors did not differ in rates of employment or marital status.
      However, special educational services were more frequently offered, and the level
      of completed education was lower. CONCLUSION: RB has influenced the lives of most
      survivors and, even though their prognosis was good, illness-related restrictions
      are common. Especially fear of developing SPT and of further loss of vision are
      important life-long problems, and many survivors had special education needs. The
      ICF might serve as a bridge between families and professionals, because this
      classification may facilitate early detection of problems.

PMID- 19760767
TI  - Detection of residual B precursor lymphoblastic leukemia by uniform gating flow
      cytometry.
AB  - BACKGROUND: Residual disease (RD) is an important prognostic factor in acute
      lymphoblastic leukemia (ALL). Flow cytometry (FC)-based RD detection is easy to
      perform, but interpretation requires expert analysis due to individual
      differences among patients. PROCEDURE: We focused at the design of standardized
      and reproducible RD monitoring in ALL. RD was investigated by a uniform gating
      strategy, which was designed internationally and tested in one center by Ig/TCR
      rearrangements. RESULTS: For each gate, positivity cutoff value was assigned
      using quantification of non-leukemic background. Comparing to Ig/TCR at 0.1%
      level, 80 of 103 specimens were correctly diagnosed by FC. The predictive value
      of FC RD at day 15 was then analyzed. In B lineage ALL, day 15 FC significantly
      correlated with Ig/TCR results at day 33 and/or week 12 (P < 0.01). No
      significant correlation was found in T lineage ALL. CONCLUSIONS: Thus, FC with
      preset uniform gating at day 15 predicts PCR-detectable MRD in B precursor ALL.
      Presented data may be used to define new polychromatic cytometric diagnostics of
      MRD including semiautomatic assessment. Pediatr Blood Cancer 2010; 54:62-70. (c)
      2009 Wiley-Liss, Inc.

PMID- 19760768
TI  - Occult fallopian tube carcinoma detected in routine pelvic washing specimens
      submitted for staging: another justification for pelvic washing cytology?
AB  - Peritoneal washing cytology is important in the staging, prognosis, and treatment
      schema for women diagnosed with gynecologic malignancies. Additionally,
      peritoneal washings are often performed before the specific diagnosis or even the
      distinction between benign or malignant lesion is known. Occasionally, the
      cytology and surgical pathology specimens, although obtained during the same
      procedure, will show unexpected and/or discordant findings. Perhaps, the greatest
      dilemma occurs when atypical cells suggestive of malignancy are identified in
      peritoneal washing specimens when a corresponding benign or discordantly low
      grade malignant diagnosis is made in the surgical pathology specimen. We present
      two such cases in which further investigation proved extremely valuable, not only
      leading to resolution of initially discrepant cytologic and surgical pathology
      findings but also in the process leading to second diagnoses of early fallopian
      tube carcinoma. Increasing evidence appears to be pointing to the fallopian tube
      as the site of origin of many serous carcinomas previously thought to be of
      primary pelvic or ovarian origin. These cases further confirm the utility of
      peritoneal washing cytology as a diagnostic modality when routine gross
      examination and sampling of the surgical specimens alone would have failed to
      provide the complete diagnosis.

PMID- 19760769
TI  - The use of p16(INK4A) immunocytochemistry in "Atypical squamous cells which
      cannot exclude HSIL" compared with "Atypical squamous cells of undetermined
      significance" in liquid-based cervical smears.
AB  - Even though p16(INK4a) (p16) immunocytochemistry has proven a useful accessory
      tool verifying the identification of atypical squamous cells of undetermined
      significance (ASC-US) categorized smears, the procedure still has limitations. To
      date few studies examining the usefulness of p16 immunocytochemistry in atypical
      squamous cells which cannot exclude HSIL (ASC-H), compared with ASC-US in liquid
      based cervical smears. Therefore, we examined the correlation of p16
      immunocytochemical staining with follow-up biopsy results on ASC-H categorized
      smears and compared the data with those classified as ASC-US on 105 liquid-based
      cytology samples. We found no statistical significance in the p16 expression of
      ASC-US smears and the presence of squamous intraepithelial lesions (SIL) in
      follow-up biopsies (p = 0.546). However, p16 expression did significantly
      correlate with the presence of SIL (p = 0.002) in ASC-H smears. There was a
      statistically significant relationship between p16 expression and presence of
      high grade squamous intraepithelial lesions (HSIL) or more on the follow-up
      biopsies in both ASC-US (p = 0.012) and ASC-H (p < 0.001) categorized smears. In
      ASC-US categorized smears, there was no statistical significance between p16
      expression and the HR-HPV viral load (p = 0.091). But there was a statistical
      significance between p16 expression and the HR-HPV viral load (p < 0.001) in ASC
      H categorized smears. Our results indicate that p16 immunostaining is a much
      better useful marker for HR-HPV infection and detection of SIL in ASC-H
      categorized smears compared to those defined as ASC-US.

PMID- 19760770
TI  - End of life in children with cancer: experience at the pediatric oncology
      department of the istituto nazionale tumori in Milan.
AB  - BACKGROUND: Coping with end-stage pediatric cancer patients and the related
      bereavement is a challenge for all the caregivers involved. PROCEDURE: Forty
      seven cancer patients who died in 2006 were assessed as concerns the main place
      of care in the end stage of their disease, their symptoms, the palliative
      treatments received, and the site of death. RESULTS: The end stage was managed at
      the Istituto Nazionale Tumori Pediatric Oncology Department in 61% of cases, at
      home in 26%, and in hospices or other hospital facilities in 11%. Pain was the
      most common symptom, followed by asthenia, anorexia, dyspnea, and
      nausea/vomiting. About half the patients died at home, 8.5% at our institute, 43%
      at other hospitals, and 8.5% in hospices. CONCLUSIONS: The care of pediatric
      cancer patients during the end stage of their disease is the responsibility of
      the caregivers who have followed them up since their diagnosis. However, it would
      be useful to establish an exchange of information and expertise between pediatric
      oncologists and the other facilities involved (hospices, other hospitals) or
      people assisting patients at home (family, family pediatrician/general
      practitioner GP).

PMID- 19760771
TI  - Critical illness polyneuropathy: a rare but serious adverse event in pediatric
      oncology.
AB  - Critical illness polyneuropathy (CIP) may aggravate sepsis and multiorgan
      dysfunction in pediatric oncology patients characterized by quadriparesis and
      difficult weaning from mechanical ventilation. Here, we report on an adolescent
      patient with acute lymphoblastic T-cell leukemia who developed critical illness
      neuropathy after an episode of sepsis with need for mechanical ventilation and
      intravenous catecholamines. Differential diagnoses like vincristine-induced
      polyneuropathy, anterior lumbosacral radiculopathy (ALR), Guillain-Barre
      syndrome, and chronic inflammatory demyelinating polyneuropathy - all occurring
      in pediatric patients with acute leukemia - are discussed.

PMID- 19760772
TI  - Treatment results of the Ewing sarcoma of bone and prognostic factors.
AB  - BACKGROUND: The purpose of this study is to assess the clinical outcome of
      patients with ESFT of the bone treated with the European Intergroup Cooperative
      Ewings Sarcoma Study (EICESS)-92 treatment protocol at a single center, and to
      identify prognostic factors. METHODS: Ninety-eight patients younger than 18 years
      of age, diagnosed with ESFT of the bone between 1992 and 2005, were analyzed
      retrospectively. RESULTS: Eighty-seven patients were treated with the EICESS-92
      protocol. The median follow-up was 105 +/- 38 months. The 5-year event-free
      survival (EFS) survival rate was 40%, the 5-year overall survival (OS) rate was
      47%. For non-metastatic disease, the rates of 5-year EFS and OS were 45% and 51%.
      These rates were 18% and 27%, for metastatic disease. The 5-year EFS and OS rates
      were 17% and 30%, respectively for females. For males, theses rates were 45% and
      48%. Of 87 patients, 52 were admitted with primary extremity lesions. Distant
      metastasis was detected in 48% of patients with a metaphyseal tumor. In patients
      with diaphyseal lesions, it was 17%. The 5-year EFS and OS were 35% and 43%,
      respectively. In non-metastatic disease, these measures were 43% and 50%, whereas
      in metastatic disease, they were 20% and 27%. In patients with a lesion
      originating from metaphysis, the 5-year EFS was 17%, and the 5-year OS was 29%,
      for patients with a diaphyseal lesion, these values were 50% and 54%. CONCLUSION:
      The presence of metastasis was closely related with metaphyseal tumors. The
      localization of tumor in the bone (i.e., diaphyseal or metaphyseal) and gender of
      patients seem to have prognostic importance.

PMID- 19760773
TI  - Successful radiation therapy for supratentorial primitive neuroectodermal tumor
      and epidermolysis bullosa simplex.
AB  - Epidermolysis bullosa simplex (EBS) is a heritable skin disorder characterized by
      skin fragility and blistering. While its most severe variant, dystrophic
      epidermolysis bullosa (DEB) is associated with squamous cell carcinoma (SCC), the
      development of extracutaneous neoplasms in EBS is extremely rare. We report a
      novel case of supratentorial primitive neuroectodermal tumor (sPNET) in a 7-year
      male with EBS. Experience of radiation therapy and its challenges in children
      with EBS has rarely been reported.

PMID- 19760774
TI  - Acquired monosomy 7 myelodysplastic syndrome in a child with clinical features
      suggestive of dyskeratosis congenita and IMAGe association.
AB  - We describe a case of acquired monosomy 7 myelodysplastic syndrome (MDS) in a boy
      with congenital adrenocortical insufficiency, genital anomalies, growth delay,
      skin hyperpigmentation, and chronic lung disease. Some of his clinical
      manifestations were suggestive of dyskeratosis congenita (DC), while other
      features resembled IMAGe association. DC has been linked to mutations in telomere
      maintenance genes. The genetic basis of IMAGe association is unknown, although
      mice harboring a mutation in a telomere maintenance gene, Tpp1, have adrenal
      hypoplasia congenita. We considered the possibility that this patient has a
      defect in telomere function resulting in features of both DC and IMAGe
      association.

PMID- 19760775
TI  - Ileal pouch for everyone, even when we are not sure of the diagnosis before or at
      colectomy?

PMID- 19760776
TI  - Body mass index and disease activity at treatment initiation: potential new
      predictors of response to azathioprine therapy in IBD.

PMID- 19760777
TI  - Autologous stem cell transplant in a patient with Down syndrome and relapsed
      Hodgkin lymphoma.
AB  - Children with Down syndrome (DS) are at increased risk for the development of
      acute leukemia but they rarely develop other hematologic malignancies or solid
      tumors. Despite aggressive supportive care, DS patients have increased risk of
      treatment related morbidity and mortality compared to other children. There are
      few reported cases of Hodgkin disease in children with DS, and no reported cases
      of successful therapy for patients with relapsed disease. We report on a child
      with DS and relapsed Hodgkin disease who was successfully treated with high-dose
      chemotherapy and autologous stem cell transplant.

PMID- 19760778
TI  - Association between Helicobacter pylori infection and inflammatory bowel disease:
      a meta-analysis and systematic review of the literature.
AB  - BACKGROUND: Epidemiologic data suggest a protective effect of Helicobacter pylori
      infection against the development of autoimmune disease. Laboratory data
      illustrate H. pylori's ability to induce immune tolerance and limit inflammatory
      responses. Numerous observational studies have investigated the association
      between H. pylori infection and inflammatory bowel disease (IBD). Our aim was to
      perform a systematic review and meta-analysis of this association. METHODS:
      Medline, EMBASE, bibliographies, and meeting abstracts were searched by 2
      independent reviewers. Of 369 abstracts reviewed, 30 promising articles were
      reviewed in detail. Twenty-three studies met our inclusion criteria (subject N =
      5903). Meta-analysis was performed with the metan command in Stata 10.1. RESULTS:
      Overall, 27.1% of IBD patients had evidence of infection with H. pylori compared
      to 40.9% of patients in the control group. The estimated relative risk of H.
      pylori infection in IBD patients was 0.64 (95% confidence interval [CI]: 0.54
      0.75). There was significant heterogeneity in the included studies that could not
      be accounted for by the method of IBD and H. pylori diagnosis, study location, or
      study population age. CONCLUSIONS: These results suggest a protective benefit of
      H. pylori infection against the development of IBD. Heterogeneity among studies
      and the possibility of publication bias limit the certainty of this finding.
      Further studies investigating the effect of eradication of H. pylori on the
      development of IBD are warranted. Because environmental hygiene and intestinal
      microbiota may be strong confounders, further mechanistic studies in H. pylori
      mouse models are also necessary to further define the mechanism of this negative
      association.

PMID- 19760779
TI  - Epstein-Barr virus and parvovirus B19 coinfection in a Crohn's disease patient
      under azathioprine.

PMID- 19760780
TI  - Plasma chromogranin A in patients with inflammatory bowel disease: a possible
      explanation.

PMID- 19760781
TI  - Effect of EP4 agonist (ONO-4819CD) for patients with mild to moderate ulcerative
      colitis refractory to 5-aminosalicylates: a randomized phase II, placebo
      controlled trial.

PMID- 19760782
TI  - Current thinking on recurrence: does anastomotic surgical technique affect
      recurrence rates in Crohn's patients?

PMID- 19760786
TI  - Between the covers: this month's main articles.

PMID- 19760783
TI  - Incidence of stricturing and penetrating complications of Crohn's disease
      diagnosed in pediatric patients.
AB  - BACKGROUND: The development of disease complications is poorly characterized in
      pediatric patients with Crohn's disease (CD). METHODS: We retrospectively
      determined the cumulative incidence of stricturing and penetrating complications
      of CD prior to first surgery utilizing data from 989 consecutively enrolled CD
      patients (age 0-17 years at diagnosis) collected between January 2000 and
      November 2003 and stored in the Pediatric IBD Consortium Registry. RESULTS: Mean
      age at diagnosis was 11.5 +/- 3.8 (standard deviation) years. Median follow-up
      time was 2.8 years. Prior to first surgery, the cumulative incidence of
      stricturing or penetrating complications was 27% at 5 years and 38% at 10 years
      from the diagnosis of inflammatory bowel disease. The cumulative incidence of
      complicated disease was lowest in isolated colonic disease (P = 0.009).
      Penetrating complications that followed stricturing complications prior to first
      surgery occurred within 2 years of stricturing complications (cumulative
      incidence was 13% at 2 years from diagnosis of stricturing disease). Stricturing
      complications that followed penetrating complications prior to first surgery
      occurred within 8 years of penetrating complications (cumulative incidence was
      26% at 8 years from diagnosis of penetrating complications). CONCLUSIONS:
      Strictures, abscesses, and fistulas are common in pediatric CD. Earlier
      aggressive management may be indicated. Prospective study is required to identify
      genetic and serologic markers that predict a patient's risk for the development
      of complicated disease and to determine optimal treatment regimens.

PMID- 19760787
TI  - Location of myofiber damage in skeletal muscle after lengthening contractions.
AB  - High-force lengthening contractions are associated with muscle damage and pain,
      and the muscle-tendon junction is commonly cited as the primary area where
      myofiber damage occurs. We induced injury in the rat tibialis anterior muscle and
      acquired magnetic resonance imaging (MRI) images postinjury. We also assayed
      membrane damage and quantified the number of centrally nucleated myofibers
      throughout the injured muscles. Results suggest that myofiber injury occurs
      primarily in the middle portion of the muscle, with interstitial edema in the
      middle and distal portions.

PMID- 19760788
TI  - Compound muscle action potential temporal dispersion during hypokalemia.

PMID- 19760789
TI  - CXCR4 enhances engraftment of muscle progenitor cells.
AB  - Cell-based therapy is a possible avenue for the treatment of Duchenne muscular
      dystrophy (DMD), an X-linked skeletal muscle-wasting disease. We have
      demonstrated that cultured myogenic progenitors derived from the adult skeletal
      muscle side population can engraft into dystrophic fibers of non-irradiated, non
      chemically injured mouse models of DMD (mdx(5cv)) after intravenous and
      intraarterial transplantation, with engraftment rates approaching 10%. In an
      effort to elucidate the cell-surface markers that promote progenitor cell
      extravasation and engraftment after systemic transplantation, we found that
      expression of the chemokine receptor CXCR4, whose ligand SDF-1 is overexpressed
      in dystrophic muscle, enhances the extravasation of these cultured progenitor
      cells into skeletal muscle after intraarterial transplantation. At 1 day post
      transplantation, mice that received CXCR4-positive enhanced green fluorescent
      protein (eGFP)-positive cultured cells derived from the skeletal muscle side
      population displayed significantly higher amounts of eGFP-positive mononuclear
      cells in quadriceps and tibialis anterior than mice that received CXCR4-negative
      eGFP-positive cells derived from the same cultured population. At 30 days
      posttransplantation, significantly higher engraftment rates of donor cells were
      observed in mice that received CXCR4-positive cells compared with mice
      transplanted with CXCR4-negative fractions. Our data suggest that CXCR4
      expression by muscle progenitor cells increases their extravasation into skeletal
      muscle shortly after transplantation. Furthermore, this enhanced extravasation
      likely promotes higher donor cell engraftment rates over time.

PMID- 19760790
TI  - An analysis of disease severity based on SMN2 copy number in adults with spinal
      muscular atrophy.
AB  - To evaluate the effect of SMN2 copy number on disease severity in spinal muscular
      atrophy (SMA), we stratified 45 adult SMA patients based on SMN2 copy number (3
      vs. 4 copies). Patients with 3 copies had an earlier age of onset and lower
      spinal muscular atrophy functional rating scale (SMAFRS) scores and were more
      likely to be non-ambulatory. There was, however, no difference between the groups
      in quantitative muscle strength or pulmonary function testing. Functional scale
      may be a more discriminating outcome measure for SMA clinical trials.

PMID- 19760791
TI  - Postoperative outcomes and reliability of "sensation-sparing" sural nerve biopsy.
AB  - Sural nerve biopsy is a valuable tool for the diagnosis of neuropathic disorders.
      However, concerns of persisting pain and numbness resulting from traditional
      whole sural nerve biopsy have led to interfascicular dissection techniques with
      inconsistent benefits over whole nerve biopsy. In this study we describe a novel
      technique of atraumatic anterior fascicular sural nerve biopsy designed to
      preserve calcaneal sensation while maintaining diagnostic benefit, without
      requiring significant interfascicular dissection. A 10-year chart review was
      conducted to identify patients who underwent anterior fascicular sural nerve
      biopsy. Pathology reports were reviewed to confirm specimen adequacy, and
      clinical notes were reviewed to determine if a diagnosis was rendered.
      Retrospective questionnaires were conducted to evaluate perioperative and long
      term sequelae and patient satisfaction. The proportion of patients with symptoms
      involving the heel versus the dorsolateral foot was evaluated with Fisher's exact
      test. Specimens from all 53 patients were acceptable and permitted a diagnosis.
      Twenty-two patients completed the retrospective survey with an average follow-up
      of 5 years (1.2-11.4 years). Eight patients (34%) experienced numbness of the
      dorsolateral foot, and 1 patient (4.5%) reported numbness of the lateral heel
      that lasted >6 months (P = 0.001). Persistent dorsolateral foot pain and cold
      sensitivity were reported by 5 patients (22.7%), but no patients reported lateral
      heel symptoms (P = 0.04). Symptoms were noted by patients most commonly while
      standing or walking, but they did not result in functional impairment in any
      case. Atraumatic anterior fascicular sural nerve biopsy predictably preserved
      essential lateral heel sensation in patients with neuropathic disorders while
      providing diagnostic utility.

PMID- 19760792
TI  - Hemorheological, morphological, and oxidative changes during ischemia-reperfusion
      of latissimus dorsi muscle flaps in a canine model.
AB  - Although ischemia-reperfusion (I/R) strongly influences muscle flap survival in
      reconstructive surgery, there is limited knowledge about its relation to
      hemorheological parameters and oxidative stress markers in flaps. In the present
      study we investigated these changes during I/R of latissimus dorsi muscle (LDM)
      flaps in beagle dogs. In four animals LDM flaps were prepared bilaterally. The
      right side served as control, while the left side's vascular pedicle was clamped
      for 60 minutes, and a 60-minute reperfusion was allowed afterward. Blood samples
      (0.5 ml each) were taken from the pedicle's vein bilaterally before and after the
      ischemia, and at the 5th, 15th, 30th, 45th, and 60th minutes of the reperfusion,
      for hematological and erythrocyte aggregation tests. In muscle biopsies, taken
      before and after I/R, histological investigations and tests for measuring
      gluthation-peroxidase (GSH-PX) activity, glutathione (GSH) and carbonyl
      concentrations, and thiobarbituric acid reactive substances (TBARS) content were
      carried out. In I/R side leukocyte count increased during the reperfusion with a
      peak at the 30th minute. Hematocrit continuously increased from the 15th minute.
      In the first 5 minutes of the reperfusion, erythrocyte aggregation increased,
      than tented to be normalized. In muscle homogenates GSH-PX activity did not
      change markedly, GSH content slightly decreased, carbonyl and TBARS content
      increased during reperfusion. A 1-hour ischemia and reperfusion of LDM flaps
      caused local changes of leukocyte distribution and erythrocyte aggregation,
      supposedly due to the metabolic and inflammatory reactions. Oxidative damage
      during reperfusion was also demonstrated.

PMID- 19760793
TI  - The current role of the vascularized-fibular osteocutaneous graft in the
      treatment of segmental defects of the upper extremity.
AB  - Large osseous defects of the upper extremity can be a challenging problem for the
      reconstructive surgeon. There are numerous treatment options reported in the
      literature with variable results. We review our experience with the vascularized
      fibular osteocutaneous graft for these complex defects with a focus on surgical
      techniques and outcomes.

PMID- 19760794
TI  - Genotyping of 73 UM-SCC head and neck squamous cell carcinoma cell lines.
AB  - BACKGROUND: We established multiple University of Michigan Squamous Cell
      Carcinoma (UM-SCC) cell lines. With time, these have been distributed to other
      labs all over the world. Recent scientific discussions have noted the need to
      confirm the origin and identity of cell lines in grant proposals and journal
      articles. We genotyped the UM-SCC cell lines in our collection to confirm their
      unique identity. METHOD: Early-passage UM-SCC cell lines were genotyped and
      photographed. RESULTS: Thus far, 73 unique head and neck UM-SCC cell lines (from
      65 donors, including 21 lines from 17 females) were genotyped. In 7 cases,
      separate cell lines were established from the same donor. CONCLUSIONS: These
      results will be posted on the UM Head and Neck SPORE Tissue Core website for
      other investigators to confirm that the UM-SCC cells used in their laboratories
      have the correct features. Publications using UM-SCC cell lines should confirm
      the genotype.

PMID- 19760795
TI  - Primary salivary gland type carcinoma of the nasopharynx: therapeutic outcomes
      and prognostic factors.
AB  - BACKGROUND: Primary salivary gland type nasopharyngeal carcinoma (SNPC) is a rare
      malignancy with diverse clinical behavior and different prognoses. Previous
      studies have reported on limited patient populations, and few long-term studies
      have outlined outcomes and prognostic factors. Furthermore, controversy exists as
      to the treatment policy of SNPC. The aim of this study was to define management
      approaches, therapeutic outcomes, and prognostic factors of SNPC. METHODS: The
      medical records of 67 patients with SNPC at 1 institution between 1977 and 2005
      were reviewed. Patient records were analyzed for management approaches, outcomes,
      and prognostic factors. RESULTS: SNPC is a rare malignancy accounting for only
      0.29% of nasopharyngeal malignancies, and the lymphatic metastases and distant
      metastases rates were 28.4% and 23.9%, respectively. The 5-year disease-free
      survival (DFS) and overall survival (OS) rates were 41.1% and 57.1%,
      respectively; no significant differences were found in DFS or OS between
      different histological subtypes. A significant difference was found in OS between
      surgical treatment and nonsurgical treatment in T1-T2 patients with well
      differentiated tumors. Multivariate analyses indicated that lymph node
      metastases, stage, and distant metastases were independent factors for DFS,
      whereas cranial nerve invasion, tumor residue, and distant metastases were
      independent factors affecting OS. CONCLUSIONS: SNPC is a malignancy with
      generally favorable prognosis. In T1-T2 patients with well-differentiated tumors,
      SNPC should be treated by combined surgical operation and radiotherapy. Cranial
      nerve invasion, tumor residue, and distant metastases were independent factors
      affecting OS.

PMID- 19760796
TI  - Possible graft-versus-host disease involving the central nervous system soon
      after cord blood transplantation.

PMID- 19760797
TI  - Profound neutropenia resulting from metyrapone-induced adrenal crisis.

PMID- 19760798
TI  - Tertiary butyl alcohol in drinking water induces phase I and II liver enzymes
      with consequent effects on thyroid hormone homeostasis in the B6C3F1 female
      mouse.
AB  - Tertiary butyl alcohol (TBA) was administered to groups of 15 female B6C3F1 mice
      in drinking water at concentrations of 0, 2.0 or 20 mg TBA ml(-1), for 14 days,
      for assessment of gross and histological changes in the liver and thyroid,
      thyroid hormones (T3, T4, and TSH), total hepatic cytochrome P450 (Cyp) content,
      specific Cyp activities and quantitative PCR analysis of specific Cyp enzymes
      (Cyp1a1, Cyp2b9, Cyp2b10, Cyp3a11), sulfuryltransferases (ST1a1, ST2a2, and STn)
      and glucuronyltransferases (UGT1a1, UGT2b1, and UGT2b5). Phenobarbital (PB) was
      administered to a positive control group by oral gavage at a daily dose of 80 mg
      kg(-1). TBA caused, on day 14, a reduction in circulating T3 (12-15% decrease)
      and a dose-dependent reduction in T4 (13-22% decrease), with no evidence of
      thyroid pathology. Two of five livers examined in the 20 mg TBA ml(-1) dose group
      showed mild, diffuse centrilobular hypertrophy. On day 14, Cyp 7-benzoxyresorufin
      O-debenzylase activity was significantly induced 12-fold by TBA at 20 mg ml(-1),
      and 1.8-fold at the 2.0 mg TBA ml(-1) concentration. Cyp 7-pentoxyresorufin-O
      dealkylase activity was slightly induced (2.1-fold) by 20 mg TBA ml(-1) on day
      14. Quantitative PCR analysis of gene transcripts showed a significant induction
      of Cyp2b10 and ST1a1 with both TBA concentrations, and a slight induction of
      Cyp2b9 at 20 mg TBA ml(-1) only. PB induced all phase I and phase II gene
      transcripts except for Cyp1a1 and Cyp2b9. These findings suggest that TBA, at and
      below doses used in chronic studies, is an inducer of phase I and phase II liver
      enzymes, with resulting decreases in circulating thyroid hormones in B6C3F1 mice.

PMID- 19760799
TI  - Hand arthritis.  Preserving joint mobility.

PMID- 19760800
TI  - Statins may reduce risk of prostate cancer.

PMID- 19760801
TI  - Herbal supplements.  Risks to your health.

PMID- 19760802
TI  - I've heard of a lot of home remedies for soothing a bee sting.  What works best?

PMID- 19760803
TI  - Are obstetricians following best-practice guidelines for addressing pregnancy
      smoking? Results from northeast Tennessee.
AB  - BACKGROUND: In 2000, the American College of Obstetricians/Gynecologists(ACOG)
      established the 5 A's method of brief smoking cessation counseling (ask, advise,
      assess, assist, arrange) as a standard component of prenatal care. The purpose of
      this study was to describe use of the 5 A's in prenatal care in Northeast
      Tennessee, where pregnancy smoking rates are three times the national average,
      and to evaluate provider attitudes toward addressing pregnancy smoking. METHOD:
      Surveys were distributed to all obstetric practices in a6-county area. RESULTS:
      One-quarter of respondents indicated they always asked pregnant patients about
      smoking, with two-thirds always giving their pregnant smokers advice to quit.
      Over half reported always assessing willingness to quit, while one-quarter or
      fewer always provided quit assistance, or arranged follow up. Over half believed
      addressing smoking was of significant value. Secondhand smoke was infrequently
      addressed. Demographics, efficacy, and outcome beliefs predicted use of the 5
      A's. CONCLUSIONS: Most obstetric providers in Northeast Tennessee are not
      following ACOG recommendations for pregnancy smoking. Efforts to address
      pregnancy smoking and associated adverse pregnancy outcomes in the region should
      include facilitation of smoking cessation interventions in prenatal care.

PMID- 19760804
TI  - Atrial fibrillation and managed care: current approaches and future directions
      for long-term therapy. Introduction.

PMID- 19760805
TI  - Retraction notice to "Why proteins evolve at different rates: the functional
      hypothesis versus the mistranslation-induced protein misfolding hypothesis" [FEBS
      Lett. 583 (2009) 1053-1059].

PMID- 19760806
TI  - Preliminary questions before studying mild traumatic  brain injury outcome.
AB  - OBJECTIVES: To point out from the literature the issues in mild traumatic brain
      injury outcome. METHODOLOGY-RESULTS: The literature review allows to point out
      several different factors involved in the difficulty to study mild traumatic
      brain injury: mild traumatic brain injury definition, postconcussional syndrome
      definition, diagnosis threshold, severity and functional symptoms outcome,
      neuropsychological tests, unspecific syndrome feature, individual factors,
      confounding factors and treatment interventions. DISCUSSION-CONCLUSION: The mild
      traumatic brain injury outcome study is complicated by the definitions issues and
      especially their practical use and by the multiplicity and the intricate
      interrelationships among involved factors. The individual outcome and social cost
      weight is widely emphasized for an event still considered as medically trivial.
      The well-ordered preventive interventions necessity and the targeted treatment
      programs need for the persisting postconcussive symptoms complete our critical
      review.

PMID- 19760807
TI  - [Update in kidney and cardiovascular diseases. Introduction].

PMID- 19760808
TI  - EASL International Recognition Awardee 2009: Prof. Ding-Shinn Chen.

PMID- 19760809
TI  - EASL Recognition Awardee 2009: Prof. Raoul Poupon.

PMID- 19760810
TI  - EASL Recognition Awardee 2009: Prof. Daniel Shouval.

PMID- 19760811
TI  - Proceedings of the 4th Workshop on Integrated Cardiovascular Repair. Innsbruck,
      Austria. December 4-6, 2008.

PMID- 19760812
TI  - [Oncology forum in urology].
AB  - OBJECTIVE: To present to the radiation oncologist the main advances in prostate
      cancer in the last year METHODOLOGY: A review of the main congress in uro
      oncology (ASCO, ASTRO, AUA, EAU) and international literature RESULTS: The
      increase in the incidence of prostate cancer without increasing in mortality must
      be a signal for oncologist to propose active surveillance to the patients without
      bad prognostic factors. Use of biomarkers could probably facilitate the selection
      of patients needing treatment. After prostatectomy, adjuvant radiotherapy could
      decrease the biochemical relapse rate but also the risk of distant metastasis,
      particularly for pT3 R1 patients; but the optimal time to deliver this post
      operative radiotherapy is discussed: immediately after surgery or delayed in case
      of PSA relapse (> or = 0,2 ng/ml). For locally advanced disease, combination of
      radiotherapy and long-term androgen deprivation improved survival over hormonal
      treatment alone. But duration of androgen deprivation must be adapted to the
      comorbidities of the patient because of the risk of metabolic syndrome. The value
      of dose escalation in association with hormonal treatment must be defined.
      CONCLUSION: Important advances in prostate cancer management have been made
      during the last months, but inclusion of patients into on-going prospective
      studies is still important to continue to improve the therapeutic results.

PMID- 19760813
TI  - Arterio-venous fistula of upper arm observed with injection abscess.

PMID- 19760814
TI  - Patient Information. Why can't I have an orgasm?

PMID- 19760815
TI  - Abstracts of the 80th Annual Scientific Meeting of the Aerospace Medical
      Association, May 3-7, 2009, Los Angeles, California, USA.

PMID- 19760817
TI  - Sleep 2009. Abstracts of the 23rd Annual Meeting of the Associated Professional
      Sleep Societies, LLC. June 6-11, 2009. Seattle, Washington, USA.

PMID- 19760816
TI  - Quality and Outcomes in Mental Health Policy and Economics. Abstracts of the 9th
      Workshop on Costs and Assessment in Psychiatry, March 27-29, 2009, Venice, Italy.

PMID- 19760818
TI  - Abstracts of the 37th Annual Congress of the Netherlands Society of Psychiatry, 1
      3 April 2009, Groningen, The Netherlands.

PMID- 19760819
TI  - Abstracts of the 2009 Research Consortium, AAHPERD National Convention, March
      2009, Tampa, Florida, USA.

PMID- 19760820
TI  - Abstracts of the Annual Meeting of the Royal Belgian Society for Ear, Nose and
      Throat, Head and Neck Surgery, 14 March 2009, Brussels, Belgium.

PMID- 19760821
TI  - JAMA strikes again!

PMID- 19760822
TI  - "Health" care in crisis.

PMID- 19760823
TI  - "Regulatory teeth".

PMID- 19760824
TI  - The bilberry blues.

PMID- 19760825
TI  - Protein networks and pathway analysis. Preface.

PMID- 19760826
TI  - Lessons I've learned at the dentist.

PMID- 19760827
TI  - Does cage size affect heart rate and blood pressure of male rats at rest or after
      procedures that induce stress-like responses?
AB  - The objective of this study was to compare cardiovascular function and home-cage
      behavior of male Sprague-Dawley rats under resting conditions or after common
      husbandry and experimental procedures when the animals were housed with 3 other
      rats in cages with 920 or 1250 cm2 of floor space. Heart rate (HR), mean arterial
      blood pressure (MAP), and movement in the cage were monitored continuously by
      using radiotelemetry. The cardiovascular data are reported for a 1-h period in
      the morning before any human interventions, for the entire 12-h dark period, and
      before and after the following acute husbandry and experimental procedures:
      routine cage change; simulated cage change; restraint and subcutaneous (s.c.)
      injection; transport to another room and s.c. injection; restraint and tail-vein
      injection; witnessing tail-vein injection of a cage mate; witnessing a simulated
      decapitation; witnessing decapitation of six rats; witnessing decapitation and
      necropsy of six rats; exposure to the odors of urine and feces from stressed
      rats; exposure to the odor of dried rat blood; and being handled and weighed.
      Home-cage behaviors (sleeping, awake, moving, rearing, and grooming) also were
      scored before and after the acute procedures. Undisturbed HR in the morning was
      not different between the two housing groups; but undisturbed morning MAP and
      undisturbed nocturnal HR, MAP, and activity were significantly reduced (P<0.05)
      in rats housed in smaller cages. When animals were subjected to acute procedures,
      floor space induced a prolonged and significant effect (P<0.05) only after a cage
      change, with HR being reduced in rats housed in small cages. Sleeping behavior
      was significantly reduced (P<0.05) after many of the acute procedures, but cage
      size only slightly affected this behavior. We conclude that housing male rats in
      groups of four at 60% of the recommended cage floor space per rat does not
      produce crowding stress relative to that of rats housed at 80% of the
      recommendations. In addition, this study, coupled with our previous results,
      suggests that close interaction between group-housed rats appears to be more
      important to stress reduction than is providing increased floor space per animal.

PMID- 19760828
TI  - Use of cyanoacrylate gel as a substitute for dental cement in
      intracerebroventricular cannulations in rats.
AB  - This study was carried out to determine whether cyanoacrylate gel was suitable
      for use as a substitute for dental cement during brain implant surgery of rats.
      Intracerebroventricular (ICV) cannulations were performed in 24 rats by two
      surgeons, one with 3 years' experience in this type of surgery, and one novice,
      with only basic training performed on cadavers. Each surgeon prepared six
      randomly allocated animals using dental cement to secure the cannula and six with
      cyanoacrylate gel. Time to complete surgery was recorded. Wound healing was
      scored and body weight recorded for each animal every day for 7 days, then on day
      14 after surgery. The use of gel led to an overall reduction in surgical time of
      8 min (approximately 30%) per animal when compared with dental cement. No
      significant differences in the animals' recovery (wound healing and body weight)
      were found between surgeons or techniques. We find the use of cyanoacrylate gel
      to be a suitable and less time-consuming alternative to dental cement for ICV
      cannulations in rats.

PMID- 19760829
TI  - A novel approach for documentation and evaluation of activity patterns in owl
      monkeys during development of environmental enrichment programs.
AB  - Documenting and evaluating the appropriateness of environmental enrichment
      programs has posed a challenge to many institutions. This paper describes a
      method for documenting and evaluating activity patterns for developing an
      environmental enrichment program. A colony of owl (or night) monkeys (Aotus
      lemurinus griseimembra) at the University of Hawaii were videotaped using
      infrared sensitive cameras and the duration and frequency of numerous activities
      were scored using an ethological analysis software program (Hindsight). A number
      of activity patterns could be observed by using this method, and a baseline was
      established for the current environmental enrichment for this colony. Videotaping
      and computer analysis is a convenient method for documenting and objectively
      evaluating activity patterns for use in the development of environmental
      enrichment programs for captive primates and other species.

PMID- 19760830
TI  - Development of renal function tests for measurement of urine concentrating
      ability, urine acidification, and glomerular filtration rate in female cynomolgus
      monkeys.
AB  - This study was conducted to develop tests for evaluation of uri ne
      concentratingability, urine acidification ability, an dglomerular filtration rate
      in cynomolgus macaques. In female cynomolgus macaques, baseline urine specific
      gravity ranged from 1.005 to 1.031, and urine osmolality ranged from 182 to 1081
      mOsm/kg. A dose of 0.4 microg/kg desmopressin acetate resulted in a urine
      specific gravity that ranged from 1.019 to 1.043 and an osmolality that ranged
      from 432 to 1298 mOsm/kg. Desmopressin acetate administration increased urine
      specific gravity and osmolality in each animal evaluated. Baseline urine pH in
      these animals ranged from 6.4 to 8.2. A dose of orally administered ammonium
      chloride (0.1 g/kg) resulted in a urine pH that ranges from 4.1 to 7.1. Ammonium
      chloride administration decreased urine pH in each animal tested. Evaluation of
      glomerular filtration rate was accomplished through urine collection and timed
      blood and urine samples after oral hydration with 0.45% sodium chloride. Blood
      samples were analyzed for creatinine, osmolality, sodium, potassium, and
      chloride. Urine samples were analyzed for volume, creatinine, osmolality, sodium,
      potassium, and chloride. Creatinine clearance, osmolality clearance, and
      electrolyte fractional clearance were calculated from the values. Osmolality
      clearance ranged from 0.03 to 0.07 ml/kg/min, creatinine clearance ranged from
      1.84 to 2.53 ml/kg/min, fractional excretion of sodium ranged from 0.17% to
      0.77%, fractional excretion of potassium ranged from 4.46% to 19.87%, and
      fractional excretion of chloride ranged from 0.25% to 1.08%. The response to
      desmopressin acetate and ammonium chloride and the osmolality, creatinine
      concentration, and fractional electrolyte excretion were consistent in individual
      animals with repeat testing. No adverse events were associated with the tests.
      The results of these tests are consistent with repeat testing in individual
      animals. These tests likely can be used for clinical assessment of renal function
      in cynomolgus macaques or for collection of experimental data.

PMID- 19760831
TI  - Monitoring lab animal feeding by using subcutaneous microchip transponders:
      validation of use with group-housed rats.
AB  - Groups of three rats were fitted with subcutaneous microchip transponders
      typically used for animal identification. Each group was housed in a custom
      designed plastic cage, which contained a pellet feeder tunnel instrumented with a
      ring-type sensor. The animals were continuously videorecorded for 24 h by using
      illumination invisible to them during the dark cycle. We performed four
      experiments in which video confirmation of feeding (i.e., pellet dispensing) was
      compared to identification of a specific animal by the automated microchip
      scanning system. When the system was optimized in two experiments, the accuracy
      of feeding with detection was 96% and 99%. These figures represent 420 pellets
      dispensed per 24 h in one study and 252 pellets dispensed per 24 h in the other.
      The use of subcutaneous microchip transponders is an effective method to monitor
      the individual feeding behaviors of rats housed in groups.

PMID- 19760833
TI  - Cardiac catheterization technique in a closed-chest murine model.
AB  - Murine studies have been a mainstay of analyzing the effects of genetic
      manipulation on cardiac phenotype. Reliable and efficient methods to evaluate
      cardiac phenotype are necessary and need to be established. However, cardiac
      catheterization techniques for obtaining such data have not been standardized.
      The goal of this study was to establish a simple and less invasive technique for
      cardiac catheterization in a closed-chest mice model. Mice were anesthetized with
      a combination of ketamine and xylazine. The right common, internal, and external
      carotid arteries were isolated microscopically, and a 1.4 Fr. conductance
      catheter was inserted and advanced retrograde into the left ventricle (LV). LV
      hemodynamic parameters were measured. This simple technique enabled us to obtain
      more physiologic LV hemodynamics compared with those from open-chest models
      reported in literature. When combined with other techniques, such as
      echocardiography, more precise assessment of cardiac function can be achieved.
      Although potentially associated with a modest learning curve, this technique
      likely will be useful as a standard procedure for cardiac catheterization in
      mice.

PMID- 19760832
TI  - Mortality rates of interventional and surgical procedures performed in domestic
      juvenile farm pigs and Yucatan mini-pigs.
AB  - Perioperative and postoperative care are critical factors in cardiac
      catheterization and cardiothoracic surgical procedures. A retrospective analysis
      of mortality data in cardiovascular catheter and surgical studies performed in
      domestic juvenile swine (DJS) and Yucatan mini-swine (YMS) was conducted. A total
      of 529 animals in 35 studies were included in the analysis, which included six
      study categories: coronary stenting (Stent) and percutaneous transluminal
      coronary angioplasty (PTCA) alone; Stent and PTCA in combination with ionizing
      radiation (Stent/Rad, PTCA/Rad); myocardial ischemia (ISCH); and three non-ISCH
      surgical procedures grouped under "other surgeries" (Other Surg). Casualties were
      defined as animals that died spontaneously before the assigned termination date.
      The highest mortality rate occurred in the ISCH group (29.7% +/- 2.2%). Mortality
      of the Stent/Rad animals (26.1% +/- 6.3%) was significantly higher than those in
      the Stent and PTCA groups (12.1% +/- 3.1% and 7.9% +/- 3.2%; P< 0.05 for both).
      Similarly, mortality in the ISCH group was significantly higher than that in the
      Stent, PTCA, or Other Surg animals (29.7% +/- 2.2% versus 12.1% +/- 3.1%, 7.9% +/
      3.2%, and 3.0% +/- 3.0%, respectively; P< 0.05 for all comparisons). We did not
      observe differences between YMS and DJS. Most casualties in the ISCH group took
      place during weeks 1 (28.0% +/- 8.4%) and 4 (29.3% +/- 6.2%) after placement of
      the coronary ameroid constrictor. The majority of animals in the Stent/Rad and
      PTCA/Rad groups died within 1 week after the procedure (67.7% +/- 12.8% and 79.3%
      +/- 12.5%, respectively). We conclude that radiation therapy used in combination
      with stenting increases the mortality rate of this catheter-based procedure.
      Animals subjected to ISCH or a transcatheter procedure in combination with
      ionizing radiation should be monitored closely during the perioperative period to
      prevent unacceptably high mortality rates.

PMID- 19760834
TI  - A new surgical technique for perfusion of the epididymal fat pad in situ in rats.
AB  - We developed a new surgical technique for preparing the epididymal fat pad in
      rats for perfusion that maintains continuous blood flow. Epididymal fat pads can
      be perfused in situ using donor blood from either fed or fasted (24 h) animals.
      During the course of all perfusions, arterial and venous blood pH and gases were
      monitored and recorded. Total fatty acid (TFA) uptake and release by the
      epididymal fat depot was measured for the control and treatment perfusions;
      glycerol release was measured in all control perfusions. After addition of 14C
      glucose to the donor-blood perfusate, all radioactivity appeared in the fat pad
      effluent blood; none appeared in the host systemic blood, and this finding
      indicated that the epididymal fat pad was separated from the host vasculature
      during perfusion in situ. The results presented here demonstrate excellent tissue
      function and metabolism, as a result of the perfusion technique. Our new surgical
      method for in vivo investigation of the epididymal fat pad, an important white
      adipose tissue, likely will have many applications in the study of lipid
      transport and metabolism, hyperlipidemia, obesity, and cancer cachexia.

PMID- 19760835
TI  - Failed air supply to individually ventilated caging system causes acute hypoxia
      and mortality of rats.
AB  - Greater than 30% mortality was observed unexpectedly in rat pups of weaning age
      kept with their dams in individually ventilated cages (IVC). A subsequent
      controlled study involving an induced electrical power failure that halted
      ventilation of IVC containing rat dams and pups showed that oxygen concentrations
      in the air in individual cages were rapidly depleted to less than 10% in 1 h. In
      a separate incident during which electrical power to IVC was inadvertently
      disconnected, rats died within 60 min of loss of power to IVC. The loss of
      electrical power to IVC housing rats is potentially a life-threatening condition
      requiring an immediate response and affirms the consideration of emergency (back
      up) electrical power where these systems are used.

PMID- 19760836
TI  - Serum clinical chemistry and hematology reference values in outbred stocks of
      albino mice from three commonly used vendors and two inbred strains of albino
      mice.
AB  - Reference values for serum clinical chemistry and hematology parameters are often
      sought after when attempting to interpret clinical pathology data. Furthermore,
      the values of parameters may vary between laboratories depending on the
      techniques being used. Accordingly, laboratories should strive to generate a
      historical reference value database based upon the methods used. Published
      reference values can provide an investigator with a useful tool with which to
      begin the evaluation of data, especially if the laboratory of concern does not
      have sufficient historical data on the inbred strain or outbred stock of mouse
      being evaluated. We present the hematology and serum chemistry values of eight
      different outbred stocks and two separate inbred strains of mice in order to
      provide reference values that may aid in the scientific and medical
      interpretation of murine clinical pathology data.

PMID- 19760837
TI  - T, radial arm, and Barnes mazes.

PMID- 19760838
TI  - My most memorable manager.

PMID- 19760839
TI  - Laboratory fish: impacts of pain and stress on well-being.
AB  - The issue regarding the capacity of fishes to experience and suffer pain remains
      unresolved. Some argue that because the fundamental structures that are involved
      in pain perception and experience in mammals are not found in fishes, there is no
      potential for these animals to experience pain. Others believe that because fish
      demonstrate strong avoidance behaviors to noxious stimuli, other neurosensory
      processing systems to process pain information (yet to be identified) may have
      evolved and that the possibility for pain perception exists. Further work
      regarding the neurophysiological mechanisms and behavioral responses involved in
      nociception and potential pain perception in fishes is required and a practical
      set of indicators for well-being, such as easily identifiable morphological and
      behavioral cues, would be of value for the care and management of these animals
      (24). Apart from the ethical obligations of the investigator and those involved
      in the care of experimental species, the welfare of fish in an experimental
      setting is key to the quality of the research. Although there remains many
      unanswered questions, the wellbeing of these animals is a significant factor to
      quality science. Ensuring optimal environmental conditions in a minimal-stress
      environment is the best means for accomplishing that goal.

PMID- 19760840
TI  - Practical safety in the animal facility.

PMID- 19760841
TI  - The use of laboratory animals: an ethical balancing act.

PMID- 19760842
TI  - Crisis aftermath.

PMID- 19760843
TI  - A breath of fresh air.

PMID- 19760844
TI  - Wire mesh flooring--boon or bedevilment?

PMID- 19760845
TI  - Sudden death in an anorectic cynomolgus macaque. Fatal fasting syndrome of obese
      macaques.

PMID- 19760846
TI  - Coping with grief in the animal facility.

PMID- 19760847
TI  - Containment capabilities of animal transfer stations.
AB  - Animal-transfer and cage-changing stations are portable downdraft-filtered clean
      benches that have been specifically modified for small-rodent handling and cage
      changing from two or more sides, and that are advertised by their manufacturers
      as providing improved laboratory animal allergen control. The authors evaluated
      the dust containment capability of three such devices under exaggerated challenge
      conditions, compared design features, and conclude that animal-transfer stations
      can be a useful addition to an institutional laboratory animal allergy control
      program.

PMID- 19760848
TI  - Strategy for controlling noise and vibration during renovation of an animal
      facility.
AB  - The noise level in an animal facility is an important environmental variable that
      can adversely affect animal welfare, as well as experimental data. The authors
      describe the strategy they used to record, evaluate, and control excess noise and
      vibration during a period of renovation, while maintaining the operation of a
      research facility.

PMID- 19760849
TI  - What's best for the mouse's house: selecting an individually ventilated caging
      system.

PMID- 19760850
TI  - Collection of mouse urine for bioassays.
AB  - Rodent bioassays often require fresh, uncontaminated urine from a large number of
      mice. The authors describe a quick and simple method to collect moderate to large
      amounts of urine from individual mice using disposable plastic trays.

PMID- 19760851
TI  - The ethical analysis of dual relationships in psychotherapy.

PMID- 19760852
TI  - Professional boundaries and the ethics of dual and multiple overlapping
      relationships in psychotherapy.
AB  - The moral status of professional boundaries and the ethical nature of dual and
      multiple overlapping human relationships in contemporary clinical practice remain
      enduring problems in all health care disciplines. In this paper I explore the
      ethics of dual or multiple overlapping relationship and apply a virtue ethics
      framework to the case of psychotherapy. After clarifying the context and meaning
      of commonly used terminology, and considering what some of the key Australian
      codes of ethics relevant to psychotherapy advise about dual relationships, I
      identify some commonly occurring situations where overlapping relationships are
      unavoidable. A case study from a rural context where size, isolation, and
      community expectations profoundly impact on the capacity of a psychotherapist to
      maintain clearly defined professional therapeutic relationship boundaries is
      analysed. The rural example is pertinent. A virtue ethics approach goes some way
      toward alleviating perceptions about the nature of dual relationships that
      contribute to an enduring reticence amongst psychotherapists (and other
      professionals) to practice in rural settings. Clearly, if a dual relationship
      involves exploitation then that relationship is a boundary crossing that should
      rightly be categorised as a boundary violation. Boundary violations are
      exploitative and unethical. However, some dual relationships may involve boundary
      crossings that are not necessarily boundary violations. Despite their general
      prohibition by Australian (and many other countries') codes of ethics relevant to
      psychotherapy, I argue that in certain situations, if a psychotherapist (who
      crosses a professional relationship boundary) acts with professional integrity
      from the distinct professional role-related virtues and/or regulative ideals that
      ensure the goals of psychotherapy (to increase autonomy and psychological
      wellbeing) are met, then a dual or multiple overlapping relationship in
      psychotherapy will be ethical.

PMID- 19760853
TI  - Exploitation and double standards in research in developed countries.
AB  - If it is so obvious that international participants should share in the spoils of
      research profits, why isn't it equally obvious that participants who share
      nationality with the researchers should do so as well? I argue that if one
      believes that some form of benefit-sharing is morally obligatory in research
      conducted in developing countries, it is very hard to escape the conclusion that
      it should at least in some circumstances be thought equally obligatory in
      research conducted within the borders of developed countries. I show that
      untenable assumptions about solidarity and altruism within developed countries
      are relied upon to deny fair treatment to research participants in developed
      countries - treatment that would be considered exploitative if meted out to
      citizens in developing countries.

PMID- 19760854
TI  - Double standards and benefit-sharing: a response to Linda Barclay.

PMID- 19760855
TI  - Defining research.
AB  - An activity defined as research will attract a particular set of regulatory,
      ethical and legal responses; however, assigning a clear definition of research is
      a difficult if not impossible task. The purpose of this article is to explore and
      emphasise the various aspects of research which allow it to be characterised as a
      reviewable activity and to stimulate discussion with a view to identifying which
      class of activities warrants a regulatory response.

PMID- 19760856
TI  - Everything we always wanted to know about nephron-sparing surgery, but were
      afraid to ask.

PMID- 19760857
TI  - Contemporary status of open nephron-sparing surgery in renal cell carcinoma.
AB  - OBJECTIVES: The contemporary management of renal cell carcinoma (RCC) has changed
      significantly over the last decade. There has been a paradigm shift in the
      surgical strategy, especially for the treatment of small renal tumors using
      partial nephrectomy and minimal invasive techniques instead of radical
      neprectomy. The backgrounds are an enhanced awareness of the overall health as co
      morbid conditions and overall morbidity. One such mechanism by which radical
      surgery of renal tumors might adversely influence overall health of the patients
      is by development or worsening of chronic kidney disease, a condition associated
      with cardiovascular disease and pre-mature death. MATERIAL AND METHODS:
      Previously nephron-sparing surgery was mostly used in imperative cases. An
      increased number of incidentally detected renal cell carcinomas are diagnosed due
      to the development and increased use of imaging techniques. These incidentally
      detected tumors generally tend to be smaller and having a lower stage. RESULTS:
      The excellent results of partial nephrectomy in RCC with low operative morbidity
      and a good oncologic control, have promoted the use of nephron-sparing approach
      also in patients with a normal contralateral kidney and having tumors smaller
      than 4 and up to 7 cm. CONCLUSION: Open partial nephrectomy has become the
      recommended technique in the treatment of properly selected patients.

PMID- 19760858
TI  - Review of the current status of tumor enucleation for renal cell carcinoma.
AB  - Tumor enucleation consists of excising the tumor by blunt dissection following
      the natural cleavage plane between the peritumoral pseudocapsule and the renal
      parenchyma without removing a visible rim of healthy renal tissue. In the very
      recent years, the urological current opinion have changed from a wide skepticism
      against tumor enucleation to a wider level of acceptance based on the lack of
      correlation between the width of the resection margin and the risk of disease
      progression/local recurrence and on larger retrospective series on tumor
      enucleation with longer follow up. The aim of the present review is to report the
      technique of tumor enucleation, discuss some technical aspects that can vary
      between centers and to summarize the oncological and surgical results of this
      technique for the conservative treatment of RCC in the last 10 years; finally, to
      briefly present the pathological findings on pseudocapsule and surgical margins
      prospectively evaluated after tumor enucleation.

PMID- 19760859
TI  - Laparoscopic partial nephrectomy.
AB  - At the moment, OPN is considered to be the gold standard in nephron sparing
      surgery. LPN has become a reliable option for many patients with renal tumors up
      to 7 cm in many centres. Oncological data are promising and the requirements of
      warm ischemia time, closure of the pelvicaliceal system and hemostasis can be
      solved without increased risk for the patients involved. Nevertheless we believe,
      that safety and oncological success are essential and the surgeons ambition can
      sometimes be dangerous. Therefore one should not hesitate to either perform an
      open procedure in those cases, where tumor characteristics seem to be unfavorable
      for a laparoscopic approach or refer the patient to a centre with more
      laparoscopic experience.

PMID- 19760860
TI  - Current role of robotic assisted partial nephrectomy.
AB  - The modern urologists are nowadays greatly involved in the surgical management of
      small renal masses, where nephron sparing surgery showed adequate oncological
      results, with a saving of a great amount of healthy renal tissue. Among the
      various minimally invasive surgical options, laparoscopic partial nephrectomy
      duplicates the open technique considered the standard of referral. Robotic
      assisted partial nephrectomy, aims to add to laparoscopy all the well known
      advantages offered by the Da Vinci system, such as the 3-Dvision and 7 degree of
      freedom of surgical instruments. We reviewed the current English literature on
      robotic partial nephrectomy published in 2008-2009 with at least 20 cases, adding
      our experience of 26 cases. Although the retroperitoneoscopic approach showed to
      be feasible in selected cases, all the procedures reported were performed with a
      transperitoneal approach. Among the 106 robotic assisted partial nephrectomy
      procedures selected, the mean tumor diameter was 2.8 cm; the mean operative time
      was 148.7 min with a mean warm ischemia time of 23.8 min and the positive
      surgical margins rate was 1.8%, reflecting the learning curve of the procedure.
      Overall complications rate was 15%, although the majority were minor and
      conservatively treated. Although robotic partial nephrectomy is still in its
      infancy, it showed adequate overall results when compared to laparoscopic partial
      nephrectomy with similar results but with a reduced learning curve. Actually
      robotic partial nephrectomy should be considered a viable option for nephron
      sparing surgery both in experienced laparoscopy centers for larger lesions in
      robotic naive centers where it may become the standard option for the treatment
      of small renal masses.

PMID- 19760861
TI  - Intraoperative and postoperative complications of nephron sparing surgery:
      prevention and possible treatments.
AB  - Conservative surgery for renal cell carcinoma has been widely diffused and
      performed in the last 15 years. It showed excellent oncological results in
      imperative and then elective indications. A greater number of small renal lesions
      are now being discovered, and elective partial nephrectomy has been adopted more
      frequently for the treatment of such tumours. However results regarding morbidity
      are extremely variable in the literature and the overall complication rate after
      NSS ranges between 4% and 30%. Fortunately, better patient selection, operating
      techniques, perioperative care, and surgical experience have guaranteed a
      significant reduction of complication in the last decade. The purpose of this
      review was to assess the incidence of complications of conservative renal surgery
      for renal cell carcinoma and to discuss treatment modalities.

PMID- 19760862
TI  - Expanding indication for elective nephron-sparing surgery in renal cell
      carcinoma.
AB  - Nephron-sparing surgery is the reference standard for the management of a small
      renal masses, especially in patients with a solitary kidney or bilateral renal
      tumors. The rationale for elective partial nephrectomy is based on the risk of
      developing kidney failure and the significant percentage of benign lesions on
      final histopathologic examination. Recent studies have demonstrated comparable
      survival and recurrence rates with partial and radical nephrectomy for renal
      tumors of 4 cm or less, and it is well demonstrated that radical nephrectomy is a
      significant risk factor for the development of chronic kidney disease. The latest
      evidences indicate that the outcomes are similar after partial nephrectomy for
      selected tumors 4 to 7 cm in size. The laparoscopic partial nephrectomy showed
      functional and oncologic outcomes comparable to those after open partial
      nephrectomy. Nevertheless, laparoscopic partial nephrectomy is a technically
      demanding procedure. With increasing experience and technical refinements, the
      complications rates have decreased substantially. Simultaneously, the indications
      of laparoscopic partial nephrectomy are being carefully extended to include more
      complex tumors. The purpose of this paper was to underline the evolution of, and
      expanding indications for, a nephron-sparing approach also for renal masses
      between 4 and 7 centimeters and a normal contralateral kidney, presuming a
      careful and sensible patient selection. This option should be reserved only to
      experienced centers.

PMID- 19760863
TI  - Predicting cancer-control outcomes in patients after nephron sparing surgery.
AB  - This article focuses on prognostic factors after nephron-sparing surgery (NSS)
      for renal cell carcinoma (RCC). A variety of prognostic models has been developed
      to predict patients' outcome after surgery for RCC. The populations which these
      models have been based on, however, mainly consisted of patients undergoing
      radical nephrectomy, whereas NSS represented only a minority. On the other hand,
      NSS is increasingly gaining acceptance for unilateral small renal masses and a
      normal contralateral kidney (elective NSS). Meanwhile many large series reporting
      favourable outcomes after elective NSS have been published. Purely elective NSS
      series constantly fail to demonstrate prognostic factors due to the rarity of
      cancer relapse. In other series including larger proportions of imperative NSS
      cancer recurrence has been reported more frequently, thus prognostic capabilities
      of established prognostic factors for RCC like TNM-stage, tumour grade, tumour
      size, symptoms, histological subtypes, or necrosis could be shown. One additional
      prognostic parameter specific for NSS not applicable in a nephrectomy setting is
      imperative indication for NSS, which is associated with poorer prognosis than
      elective NSS. In contrast, positive surgical margins after NSS uniformly revealed
      no unfavourable impact. Laparoscopic NSS is increasingly performed at selected
      centres. Long-term outcome data are still very limited, longer follow-up is
      needed to conclude whether the laparoscopic approach by itself impacts on
      prognosis. At present, it is still unclear whether the published prognostic
      models are reliably applicable for the NSS population. Thus, validation of these
      models in large multi-institutional databases is encouraged.

PMID- 19760864
TI  - Pathological evaluation of peritumoral pseudocapsule status after nephron sparing
      surgery and its prognostic implication.
AB  - The presence of a capsule/pseudocapsule (PS) with signs of infiltration within
      its layers or completely penetrated could represent the first pathological
      evidence of the capacity achieved by tumor cells to infiltrate and invade
      surrounding tissue and it could eventually have a role as prognostic factor in
      patients with intracapsular renal cell carcinoma (RCC). Historical reports on the
      PS surrounding RCC date back to the mid twentieth century with the aim to define
      the possible role of conservative surgery for small renal tumors. Few authors
      have recently investigated the morphological appearance of tumor fibrous PS and
      the prognostic implication of its infiltration after kidney surgery for RCC. The
      aim of the present review is therefore to report the historical data and the
      current results of a literature review on the PS status after kidney surgery and
      to define its prognostic implication.

PMID- 19760865
TI  - Minimally invasive ablative technique for the treatment of small renal masses.
AB  - Minimally invasive nephron sparing techniques are becoming popular treatment
      modalities in the face of smaller renal tumours diagnosed in an increasingly
      elderly population. Techniques include cryoablation and radiofrequency ablation,
      delivered via percutaneous or laparoscopic approaches. Laparoscopic cryoablation
      shows the lowest recurrence rates but this must be balanced against higher
      morbidity compared to the percutaneous approaches. To date, studies are limited
      by lack of biopsy data and accurate measurement of the effects of treatment on
      renal function. Laparoscopic partial nephrectomy represents the main minimally
      invasive alternative to these ablative techniques, but remains a technically
      challenging procedure. In the short term renal cryoablation and RFA appear to
      represent safe, effective minimally invasive nephron sparing techniques in the
      treatment of small renal tumours. Further studies examining long term recurrence
      rates and renal outcome will help to determine the utility of these techniques in
      managing renal tumours.

PMID- 19760866
TI  - The current role of percutaneous needle biopsies of renal tumours.
AB  - The role of percutaneous biopsy of renal masses has been traditionally limited by
      concerns about its safety, accuracy and sampling errors. The increasing incidence
      in the diagnosis of incidental small renal masses (SRMs), the development of
      conservative and minimally invasive treatments for low risk renal cell carcinomas
      (RCCs) and the discovery of novel targeted treatments for metastatic disease are
      now leading to wider indications for renal tumor biopsy. Percutaneous biopsy of
      renal tumors can be performed in an outpatient setting under ultrasound and/or CT
      guidance. 18 gauge needles loaded in an automatic biopsy gun are used to retrieve
      cores and 21 gauge needles to obtain FNA specimens through a 17 gauge coaxial
      cannula placed close to the tumor. A careful check of the quality of biopsies and
      aspirates is paramount to maximize the diagnostic yield of the procedure. With
      the development of new biopsy techniques the risk of tumor seeding appears
      negligible and significant bleeding is unusual and very rarely clinically
      significant. In centres with expertise, needle core biopsy with or without FNA
      can provide adequate specimens for an accurate diagnosis in over 90% of cases.
      Incidental SRMs are frequently detected in elderly patients and have a very
      heterogeneous biological behaviour At surgery up to one third have benign
      histologies and most of those that are malignant are low grade RCCs. Pretreatment
      percutaneous biopsy can significantly decrease the number of unnecessary
      surgeries for benign disease and assist the urologist in clinical decision
      making, especially for elderly and unfit patients who are possible candidates for
      active surveillance and/or minimally invasive ablative therapies. Finally, there
      is potential for stratifying initial therapy of metastatic RCC by histological
      subtype on needle biopsies.

PMID- 19760867
TI  - Possibilities for future collaborative research on small renal masses (SRM's).
AB  - The diagnosis and management of small renal masses (SRM's) has led to rapid
      advances in diagnostic and surgical technologies. This paper reviews some of the
      literature and speculates about possible areas for future research.

PMID- 19760868
TI  - The influence of sodium nitrite on the locomotor functions of white blood cells.

PMID- 19760869
TI  - Immunohistochemical confirmation of localization of the ribosomal protein L26 in
      the terminal buttons of rat motor axon.

PMID- 19760870
TI  - The role of tyrosine kinases in water-electrolyte transport in amoeba A. proteus.

PMID- 19760871
TI  - Effect of serotonin deficiency on the immune system development in the rat.

PMID- 19760872
TI  - Paternal care, aggressiveness, and testosterone secretion in male mandarin voles
      (Lasiopodomys mandarinus).

PMID- 19760873
TI  - A new technique for reconstructing the cation-anion balance in lakes by diatom
      analysis.

PMID- 19760874
TI  - A novel bioregulator isolated from rat bone tissue: physicochemical properties
      and in vitro effect on cartilaginous tissue.

PMID- 19760875
TI  - The Atlg12860 gene of Arabidopsis thaliana determines cathelicidin-like
      antimicrobial activity.

PMID- 19760876
TI  - Cardiac activity and behavior of blue mussels from the Barents Sea under
      controlled conditions.

PMID- 19760877
TI  - Bacteriophages as a new trophic link in the ecosystem of the deep-water Lake
      Baikal.

PMID- 19760878
TI  - Feeding habit of the common eider Somateria mollissima in the White Sea.

PMID- 19760879
TI  - Effect of root cooling on the tolerance of wheat leaf cells and activity of the
      photosynthetic apparatus.

PMID- 19760880
TI  - Changes in the motor activity and temperature resistance of shorthorn sculpin
      Myoxocephalus scorpius (L) from the Barents Sea.

PMID- 19760881
TI  - Characteristics of the population size structure of the pine marten (Martes
      martes Linnaeus, 1758) in the species area.

PMID- 19760882
TI  - Potato resistance induced by chitosan derivatives.

PMID- 19760883
TI  - Body temperature changes in purebred and hybrid Yakut horses under the conditions
      of Yakutia.

PMID- 19760884
TI  - Changes in the chloroplast ultrastructure in potato leaves during long-term
      micropropagation in vitro.

PMID- 19760885
TI  - Changes in the common vole (Microtus arvalis) and East European vole (Microtus
      rossiaemeridionalis) social behavior after combining conspecific groups.

PMID- 19760886
TI  - Changes in the body temperature of hibernating animals of the Sciuridae family in
      the year life cycle.

PMID- 19760887
TI  - Multifractal analysis of the species structure of helminthic communities of small
      mammals in the Samarskaya Luka.

PMID- 19760888
TI  - Characteristics of the spatial distribution of nanophytoplankton in the vicinity
      of the Franz Josef Land in summer.

PMID- 19760889
TI  - Local plant species richness depends on the total area of alpine communities.

PMID- 19760890
TI  - Genetic and vocal differentiation in hybrid zones of passerine birds: Siberian
      and European chiffchaffs (Phylloscopus [collybita] tristis and Ph. [c.]
      abietinus) in the southern Urals.

PMID- 19760891
TI  - Gap junctional intercellular communication in human embryonic stem cells during
      spontaneous differentiation.

PMID- 19760892
TI  - Function of the spermatogenic system in old senescence-accelerated prone mice of
      the SAMP1 strain in chemically induced hypermutability.

PMID- 19760893
TI  - Current approach to acne management: a community-based analysis.
AB  - During fall 2008, 10 roundtable discussions involving 70 practicing
      dermatologists and a physician assistant were conducted across the United States
      to address patient considerations and treatment strategies for acne vulgaris. A
      case study format was used to initiate discussion. This supplement is based on
      the issues raised during the roundtable discussions and at a final working
      session among the authors where suggestions, trends, and the consensus from each
      of the 10 roundtable discussions were reviewed regarding published, evidence
      based recommendations for treating acne vulgaris. Effective treatment of acne
      vulgaris can prevent adverse emotional sequelae and physical scarring. We hope
      that the information presented herein will help guide our colleagues in improving
      the care of patients with acne vulgaris.

PMID- 19760894
TI  - Epidemiology of epilepsy: prevalence, impact, comorbidity and disparities.
AB  - This is a summary of four presentations on epidemiological aspects of Epilepsy in
      children and adults in Canada, given at the Canadian League Against Epilepsy 30th
      anniversary meeting in Vancouver, British Columbia in October 2007. Dr. S. Wiebe
      discusses the burden of epilepsy, Dr, P. Camfield addresses the epidemiology of
      epilepsy in children, Dr. N. Jette provides an overview of comorbidity and
      epidemiological surveillance in epilepsy, and Dr. Burneo explores the area of
      disparities in epilepsy. The summary is intended as a brief overview of these
      aspects, with particular emphasis on available Canadian data.

PMID- 19760895
TI  - Maximizing quality of life in people living with epilepsy.
AB  - Improving quality of life is now seen as a major challenge facing people with
      epilepsy. Can research on human happiness shed light on why it is that the
      wellbeing and quality of life of people with epilepsy is worse than the
      condition's clinical and medical prognosis would predict? Empirical research on
      subjective wellbeing and happiness in healthy people indicates that there are a
      small number of key factors that are related to wellbeing, including employment,
      social interactions, family relationships, and experiential activities. This
      paper reviews these crucial components of wellbeing, discusses how each factor
      applies to people living with epilepsy, and identifies epilepsy-specific factors
      such as stigma and comorbidity that contribute to low quality of life. Lastly,
      this review provides a list of program-based approaches to improving quality of
      life, as well as practical recommendations for use by practitioners and people
      living with epilepsy.

PMID- 19760896
TI  - Is functional hemispheric lateralization guided by structural cerebral asymmetry?
AB  - "Lateralized hemispheric function is guided by structural cerebral asymmetry"
      remains an attractive hypothesis. It is plausible that genetically determined
      events lead to structural asymmetry that in turn guide lateralized functional
      development. However, hemispheric specializations are neither inevitable
      consequences of early local cytoarchitectural differences nor immutably fixed in
      structure. The human brain possesses dynamic plasticity as its primary mission
      and can override and transcend hemispheric differences for preservation of higher
      cognitive functions such as speech and language.

PMID- 19760897
TI  - Kindling as a model of human epilepsy.
AB  - The evidence supporting the suggestion that kindling is a good model of human
      temporal lobe epilepsy is briefly reviewed. Parallels between the human
      condition, involving both partial and secondarily generalized seizures, and
      kindling in rats and other animals are drawn and contrasted.

PMID- 19760898
TI  - Kindling, long-term potentiation and spatial memory performance.
AB  - Kindling and long-term potentiation (LTP) are two common paradigms of synaptic
      plasticity. Initially proposed as a model of learning of memory, kindling is
      considered as a model of epilepsy, with LTP filling in its role as a model of
      learning and memory. This review suggests that LTP is not critical for kindling
      induced epileptiform activity such as spontaneous interictal spikes. Repeated
      theta-frequency primed burst stimulations (PBs) and repeated ADs (kindling) of
      the hippocampal commissures were compared in their ability to induce potentiation
      and to disrupt spatial behavior. Repeated PBs and kindling both induced large
      potentiation of the CA1 basal dendritic synapse, but only hippocampal kindling
      disrupted the retention of spatial task on the radial arm maze. While there was
      evidence that transynaptic potentiation was more persistent after hippocampal
      kindling than repeated PBs, disruption of inhibition rather than enhancement of
      excitation may more readily explain the disruption of spatial behavior by
      kindling. In conclusion, there is little evidence that LTP is essential for the
      epileptiform activity or the disruption of spatial behavior after hippocampal
      kindling.

PMID- 19760899
TI  - Mechanisms underlying behavioural comorbidities associated with kindling.
AB  - There is a substantial incidence of interictal behavioural comorbidities with
      epilepsy. These comorbidities can often be more difficult to treat than the
      seizures themselves and are a significant burden to the afflicted individuals and
      health care system. This article provides a brief overview of the behavioural
      comorbidities associated with epilepsy in humans and how the kindling of animals
      models these behavioural anomalies. Specific attention is paid to kindling in
      frontal cortex, its effects on skilled reaching behaviour and underlying
      mechanisms.

PMID- 19760900
TI  - Epilepsy and memory dysfunction.

PMID- 19760901
TI  - "I can't remember": memory deficits in children with epilepsy.
AB  - Compared with the literature on epilepsy in adults, there is relatively little
      written about memory in children. This paucity of findings exists despite the
      fact that childhood is a critical time for laying down memories that contribute
      to adult attainments. This paper reviews the evidence for memory deficits in
      children with intractable epilepsy. The nature of these deficits and their impact
      on the child's daily function are described. The evidence of neural, seizure
      related and treatment factors that contribute to these impairments is presented.

PMID- 19760902
TI  - The patient's experience of memory change after elective temporal lobe resection.
AB  - Subjective memory has emerged as a relevant indicator of outcome following
      temporal lobe resection (TLR) for the treatment of intractable temporal lobe
      epilepsy. Study 1 asks whether patients undergoing TLR experience subjectively
      perceived memory changes one year following surgery. The Memory Observation
      Questionnaire provided data for both individual and group level analyses.
      Reliable change index results indicated that most patients and informants (i.e.,
      a family or close friend) reported no change or improvement after the surgery,
      and 7.8% reported deterioration. Aggregate scores showed that mean ratings of
      subjective memory ratings significantly improved or did not change following
      surgery. Study 2 is a meta-analysis of six different publications on subjective
      memory comprising 465 TLR patients and 171 informants (i.e., 25 effect sizes).
      The weighted mean effect size of 0.27 was small, yet significantly larger than
      zero in the direction of perceived improvement. These findings suggest that most
      TLR surgical epilepsy patients do not notice post-operative changes in their
      memory function. Accordingly, we propose that a comprehensive discussion of
      surgical risks and benefits incorporates both patient impressions, along with
      objective memory outcomes.

PMID- 19760903
TI  - Intracarotid amobarbital procedure and etomidate speech and memory test.
AB  - The intracarotid amobarbital procedure (IAP) has for over 50 years been an
      important component of the presurgical investigation of patients with epilepsy
      who are candidates for surgical intervention as treatment for their seizures.
      Owing to increasing frequency and duration of amobarbital shortages, alternatives
      for this drug have been sought and implemented, but until now only the drug was
      changed, while the basic procedure remained essentially the same as that used
      with amobarbital. This paper describes the Montreal Neurological Institute
      experience using etomidate in place of amobarbital and introducing a significant
      change in the procedure: after an initial bolus injection, an infusion is used to
      maintain the level of hemianesthesia during critical test times. Results of 28
      patients tested with this procedure are compared to results from 40 patients
      tested in the standard IAP.

PMID- 19760904
TI  - Clinical intracranial overview of seizure synchrony and spread.
AB  - Ictal semiology most effectively localizes epileptogenesis, but the clinician
      must be aware of seizure propagation as an influence upon seizure manifestations.
      This article first reviews basic mechanisms of seizure spread, including
      alteration of usual routes in some patients whose seizures begin in childhood. In
      addition to intra-cortical spread, propagation pathways include the commissures,
      thalamus and brain stem. The second section reviews common clinical phenomena
      consequent to a few frequently encountered propagation patterns.

PMID- 19760905
TI  - Insular cortex epilepsy: an overview.
AB  - In this review the authors discuss insular cortex epilepsy, an under-recognized
      localization-related syndrome that may explain some temporal (but also frontal
      and parietal lobe) epilepsy surgery failures. The insula may generate a variety
      of symptoms (including visceral, motor and somatosensory) that mimic temporal,
      frontal or parietal lobe onset seizures. Intracerebral electrodes directly
      implanted in the insula are currently the only way to confirm insular seizures.
      Consideration should be given to exploration of the insular cortex in MRI
      negative patients with seizure semiology consistent with insular onset seizures.
      Electroencephalographers should have a low threshold to sample this region,
      especially in the absence of a structural lesion. Microneurosurgical technical
      advances allow resective surgery of the insula with relatively low morbidity.

PMID- 19760906
TI  - The catastrophic epilepsies.

PMID- 19760907
TI  - Reflections on the epileptic encephalopathies.
AB  - Although the epileptic encephalopathies have a profound impact on neurological
      development, there has been limited progress made in the successful treatment of
      these disorders. This article suggests that the limited understanding of the
      pathophysiology of the encephalopathies, the lack of a good animal model of these
      disorders, the failure to understand the impact of etiology on response to
      treatment, and the absence of a reliable method for measurement of cognitive
      change in response to treatment are factors that contribute to the limited
      progress.

PMID- 19760908
TI  - Metabolic epilepsies: approaches to a diagnostic challenge.
AB  - Although inborn errors of metabolism (IEM) are a relatively rare cause of
      epilepsy in children, their diagnosis is important with respect to treatment,
      prognosis and genetic counselling. In addition to seizures and epilepsy, IEM may
      produce a complex clinical picture in which epilepsy is only one of the various
      neurologic manifestations including developmental delay/regression, mental
      retardation, movement disorders, micro-/macrocephaly, as well as cerebral grey
      and white matter changes. Dysmorphic features and cerebral dysgenesis may also be
      part of a metabolic epilepsy syndrome (e.g. disorders of peroxisomal biogenesis,
      glutaric aciduria type 2, pyruvate dehydrogenease complex deficiency). Metabolic
      epilepsies may dominate the clinical presentation (e.g. pyridoxine dependent
      epilepsy) or may precede further neurologic deterioration (e.g. neuronal ceroid
      lipofuscinosis) and additional organ involvement (e.g. liver failure in Alpers
      (POLG1) disease). Metabolic epilepsies often present with myoclonic seizures
      (e.g. Gaucher Disease type 3, mitochondrial syndromes) and, as a rule, patients
      presenting with predominantly myoclonic seizures should be carefully investigated
      for these types of metabolic epilepsies. Patients with very early onset of
      epilepsy are considered at high risk for an underlying IEM as well. In this
      review we present an overview of metabolic epilepsies based on various criteria
      such as treatability, age of onset, seizure type, and pathogenetic background.
      Exemplary disorders will be described in more detail including cerebral glucose
      transporter (GLUT1) deficiency, pyridoxine dependent epilepsy, neuronal ceroid
      lipofuscinosis, cathepsin D deficiency, Alpers syndrome (POLG deficiency), and
      guanidinoacetate methyltransferase (GAMT) deficiency.

PMID- 19760909
TI  - Vitamin B6 dependent seizures.
AB  - Vitamin B6 is an abundant cofactor in aminoacid- and neurotransmitter metabolism.
      Physiologic availability depends on dietary supply, intact absorption and
      conversion of pyridoxamine and pyridoxine into the only active cofactor,
      pyridoxal-5'-phosphate (PLP) in liver. By now we know of four genetic epilepsies
      with vitamin B6 dependent seizures. Two are caused by reduced
      synthesis/availability of PLP (Pyridox(am)in-phosphate oxidase (PNPO) deficiency
      and infantile hypophosphatasia) and two by increased utilization/inactivation
      (pyridoxine-dependent epilepsy and hyperprolinemia type II). Aside from
      hyperprolinemia type II these disorders usually present with therapyresistant
      (myoclonic) seizures in the neonatal period. The EEG findings may range from
      burst suppression pattern to unspecific slowing or may even be normal. All four
      disorders can be diagnosed by reliable biomarkers and be confirmed by molecular
      analysis of the respective genes. While PLP would benefit all four entities, PNPO
      patients are typically resistant to pyridoxine and need PLP substitution.
      Especially in neonatal, therapyresistant seizures, these disorders have to be
      considered early, to prevent irreversible neurologic damage.

PMID- 19760910
TI  - Investigating epigenetic influences on seizure disposition.
AB  - Rats selectively bred to be seizure-prone versus resistant naturally exhibit
      behaviors, neuroanatomy and physiology that are reminiscent of attention deficit
      hyperactivity disorder (ADHD) and autism spectrum disorders (ASD) in humans.
      Evidence suggests these characteristics evolve via genetic/epigenetic mechanisms
      acting prior to birth that most likely involve aberrant lipid handling.

PMID- 19760911
TI  - Extratemporal "limbic" seizures--introductory remarks.

PMID- 19760912
TI  - A brief review of the anatomy and physiology of the limbic system.
AB  - The limbic system as described by Broca, Papez and MacLean is an important
      concept for clinicians and basic researchers but remains controversial. Part
      anatomy and part physiology, it is hypothesized to be the primary brain mechanism
      responsible for the well being of the animal. The limbic system processes sensory
      input from the external and internal environment to determine, through memory and
      motivation, the emotional, autonomic, motor and cognitive responses important for
      self-preservation and survival. Disruption of limbic function by ictal activity
      is most commonly seen in temporal lobe epilepsy, but seizures in other parts of
      the limbic system can result in equally disturbing consequences.

PMID- 19760913
TI  - Continuous EEG monitoring in the ICU: challenges and opportunities.
AB  - Continuous EEG monitoring (CEEG) in the ICU is increasingly recognized as
      valuable means of monitoring cerebral function, otherwise inaccessible in the
      comatose patient. The principal applications are: monitoring for seizures and
      ischemia, guiding therapy for seizures and ischemia (especially vasospasm),
      adjusting levels of sedation for paralyzed or delirious patients, charting trends
      in brain function and prognosis. Continuous EEG monitoring is faced with numerous
      challenges: electrode failures (better electrodes are needed to replace standard
      EEG electrodes), documentation in the absence of a technologist, artifacts
      peculiar to ICU, prompt interpretation and review of large amounts of data,
      resource allocation and establishing the technology as being useful in improving
      outcomes and shortening ICU and hospital length of stay.

PMID- 19760914
TI  - Status epilepticus in the pediatric ICU: state of the art.
AB  - Status epilepticus in the pediatric intensive care setting is a neurological
      emergency. Its management presents profound challenges for the pediatric
      intensivist, and neurologist. Understanding the neurobiological factors that are
      operative in transition of an epileptic seizure to self-sustained status
      epilepticus is critical to management. Statue epilepticus in children is often
      heterogeneous in etiology. In this article, I examine the evidence for who is
      likely to be admitted to the pediatric intensive care unit for management, the
      risk factors, the relationship of seizure duration and evolution to status
      epilepticus, and the reasons for seizure refractoriness. The immediate
      complications and long term consequences leading to morbidity and mortality in
      this condition are reviewed. The problem of refractory status epilepticus is
      particularly more frequently encountered in the intensive care setting.
      Therapeutic options in the initial management and in particular addressing
      reasons for the development of pharmacoresistance in status epilepticus are
      presented. Finally, data on outcome in the pediatric ICU setting is discussed
      providing thus an overview of our current understanding and state of the art in
      the management of status epilepticus in children.

PMID- 19760915
TI  - Does portal vein resection with hepatectomy improve survival in locally advanced
      hilar cholangiocarcinoma?
AB  - BACKGROUND/AIMS: Although portal vein resection (PVR) can increase the
      respectability and curability in locally invading hilar cholangiocarcinoma, there
      are still controversies in regards to the balance between the risk and the
      benefit. The present study retrospectively assessed the safety and survival
      impact of PVR in locally advanced hilar cholangiocarcinoma (HCCA). METHODOLOGY:
      259 patients undergoing surgical resection for HCCA between June 1989 and June
      2005 were divided into two groups, 51 who underwent PVR (PVR+) and 208 who did
      not (PVR-). We compared survival and clinicopathological data between these two
      groups. RESULTS: The 5-yr survival rate of PVR+ group (22.8%) was significantly
      lower than one of PVR- group (30.9%), but 7 of 51 patients (13.7%) have survived
      more than 5 yr. Five operative mortalities (9.8%) occurred in PVR+ group, but
      only 1 of 5 mortalities was directly related to PVR. The morbidity rate and
      postoperative liver function did not differ between two groups. In the PVR+
      group, 28 (54.9%) had actual tumor invasion into the portal vein, but tumor
      invasion demonstrated no effect on survival. CONCLUSIONS: Although PVR + group
      demonstrated low survival rate than PVR- group, PVR can offer long-term survival
      in more than 1 of 10 locally advanced HCCA. However, operative mortality should
      be lowered to apply PVR in hepatectomy for HCCA.

PMID- 19760916
TI  - Should we perform surgical management in all patients with suspected porcelain
      gallbladder?
AB  - BACKGROUND/AIMS: Porcelain gallbladder has generally been regarded as a risk
      factor for gallbladder cancer. This study was designed to clarify the association
      between porcelain gallbladder and cancer by analysis of clinicopathological
      features of patients who underwent surgery for suspected porcelain gallbladder.
      METHODOLOGY: From January 2002 to December 2008, 3159 cholecystectomies were
      performed at Ajou University Medical Center. Twelve patients were preoperatively
      diagnosed with suspected porcelain gallbladder. To examine the association
      between gallbladder calcification and cancer, patients who were
      histopathologically diagnosed with either gallbladder calcification or cancer
      were also reviewed. RESULTS: According to final pathology, 44.3% of patients
      showed porcelain gallbladder. During the study period, calcification of
      gallbladder wall was identified in 9 patients (0.2%). The mean age was 54.6 +/-
      15.0 years (range, 30-75). The female-to-male ratio was 3.5:1. However,
      preoperative porcelain gallbladder was diagnosed in 5 patients. Eight of 9
      patients underwent LC, whereas the remaining one patient underwent laparoscopic
      assisted distal gastrectomy. Interestingly, there was no patient with a diagnosis
      of both porcelain gallbladder and cancer. CONCLUSIONS: We found that preoperative
      diagnosis of porcelain gallbladder was difficult. Moreover, there was no
      association between porcelain gallbladder and cancer. Therefore, when porcelain
      gallbladder is suspected, surgeons should decide operation, based on the symptoms
      rather than the possibility of coexistence of gallbladder cancer.

PMID- 19760917
TI  - Laser-induced damages of different types of human gallbladder stones.
AB  - BACKGROUND/AIMS: Today, treatment of human calculi, and particularly those of
      gallbladder, is, to a large extent, less invasive procedure due to numerous non
      invasive methods that have been developed. METHODOLOGY: CO2 laser of pulse
      (output 5W)(W-watt, SI unit system) and continual mode (output 15W) and diode
      laser (808 nm-nanometer, SI) were used for tests of fragmentation of gallbladder
      calculi in vitro. RESULTS: A total of 15 human gallbladder calculi of known size
      were examined, which had been collected during surgical interventions. Damages
      caused by laser were examined visually and by stereomicroscope (10 to 25 times
      magnification). During testing, the dependence of fragmentation on the type of
      laser effect, as well as the degree of fragmentation on the type of tested
      calculus was noted. Different types and dimensions of damage caused by various
      laser beams, as well as coloration changes of superficial layers in relation to
      the type of tested calculi was noticed. CONCLUSION: Accordingly, in this specific
      case, the priority for removal of gallbladder calculi by ablation will be given
      to diode laser.

PMID- 19760918
TI  - Laparoscopic cholecystectomy in aged patients.
AB  - BACKGROUND/AIM: The life-span of humans increased and the prevalence of
      gallstones has also increased with age. The aim of this study is to examine the
      associations between age and clinical outcomes in the patients undergoing
      elective laparoscopic cholecystectomy (LC). METHODOLOGY: A total of 627 patients
      receiving LC were categorized into three different age groups. Group I was
      defined as less than 65 years of age (n = 510), group II as 65 to 79 (n = 100)
      and group III as more than 80 (n = 17). Clinical characteristics of these
      patients and surgical outcomes were analyzed. RESULTS: Rates of conversion and
      major complications were similar among three age groups. Group III had a
      significantly longer length of perioperative hospital stay compared to groups I
      or II. However, rates of minor complication appeared to be higher as age
      progressed (group I: 0.6%; group II: 6.0%; group III: 17.6%). In multivariable
      adjusted modeling, groups II and III respectively, had a 7.1-fold (95% CI: 1.3
      38.1, p = 0.023) and 34.1 (95% CI: 3.8-310.8, p = 0.002) higher risk of having
      minor complications than group I patients. CONCLUSION: LC is a safe and accepted
      procedure in aged patients with uncomplicated gallbladder stones disease, but it
      may be associated with increased postoperative morbidity.

PMID- 19760919
TI  - Partial segment-IV/V liver resection facilitates the repair of complicated bile
      duct injury.
AB  - The ability to perform a technically perfect anastomosis remains the key to
      success in bile duct repair. This report describes our technique in facilitating
      the performance of a good surgical anastomosis for difficult bile duct repair. In
      the present study are presented 3 cases of bile duct repair for a Strasberg type
      E3 stricture, a Strasberg type-E4 fistula and an anastomotic stricture of a
      previously performed choledochojejunostomy for the correction of bile duct
      injury. The approach was to perform partial resection of the lower part of
      segments IV and V. The hepatoduodenal ligament was not dissected. The anterior
      surface of the bile duct was utilized to perform Roux-en-Y hepaticojejunostomy.
      Operative times ranged from 4 to 5 hours, and Pringle times 15 to 25 minutes.
      There was no vascular injury. We were able to perform wide anastomoses,
      facilitated by excellent exposure of the hilar plate. There was no any
      complication. Partial resection of the hepatic segments IV-V provides excellent
      exposure of the hilar plate. The risk of vascular injury was minimized by
      avoiding dissection of the hepatoduodenal ligament. It is believe this technique
      may offer a superior approach to difficult repair of complicated bile duct
      injury.

PMID- 19760920
TI  - KL-6 mucin in metastatic liver cancer tissues from primary colorectal carcinoma.
AB  - BACKGROUND/AIMS: KL-6 mucin is MUC1 bearing sialylated carbohydrate epitopes
      recognized by KL-6 antibody. This study aimed to assess subcellular localization
      of KL-6 mucin in liver metastatic tissues from colorectal carcinoma and
      hepatocellular carcinoma tissues. METHODOLOGY: Tissue samples were collected from
      56 patients with liver metastasis of colorectal carcinoma and 92 patients with
      hepatocellular carcinoma who underwent a hepatectomy. Tissues were subjected to
      immunohistochemical analysis using KL-6 antibody. RESULTS: All 56 cases with
      metastatic liver cancer showed positive staining for KL-6 mucin in cancer tissues
      but not in non-cancerous tissues. All staining was observed in the
      circumferential membrane and/or cytoplasm of the cancer cells. In contrast, no
      staining for KL-6 mucin was observed in either cancerous or non-cancerous tissues
      of the 92 patients with hepatocellular carcinoma. CONCLUSIONS: KL-6 mucin may be
      an indicator for liver metastasis of colorectal carcinoma. Additionally,
      detection of KL-6 mucin may be helpful in distinguishing hepatocellular carcinoma
      from metastatic liver cancer.

PMID- 19760921
TI  - HBV infection involving in hepatic progenitor cells expansion in HBV-infected end
      stage liver disease.
AB  - BACKGROUND/AIMS: In chronic hepatitis B, hepatic progenitor cells (HPCs)
      activation and ductular reactions occurred in periportal and portal area.
      However, the association between hepatitis B virus (HBV) infection and HPCs
      activation remains unknown. We aim to investigate the expansion of HPCs in
      patients with end-stage chronic hepatitis B and its relationship to HBV
      infection. METHODOLOGY: Liver biopsy specimens from 16 cases of end-stage liver
      disease caused by chronic hepatitis B were studied. The quantities of serum HBV
      DNA were available in 13 patients. The number of HPCs and the area of ductular
      reactions were quantitively analyzed on the cytokeratin 7 (CK7)-stained sections.
      Double-staining combined either HBsAg or HBcAg with CK7 were performed to assess
      the histological relationship between HBV infection and HPCs activation. RESULTS:
      All of the sections showed liver cirrhosis and severe inflammation (HAI ranged
      from 12 to 17). The number of HPCs correlated with the area of ductular reactions
      positively. Multivariate analysis showed that serum HBV DNA level was
      independently associated with HPCs activation and ductular reactions. Moreover,
      the expression area of HBsAg in liver tissue correlated with HPCs activation
      positively. CONCLUSIONS: In end-stage of chronic hepatitis B, the expansion of
      hepatic progenitor cells and ductular reactions were extensive. HBV infection may
      be involved in the proliferation of progenitor cells in cirrhotic environments.

PMID- 19760922
TI  - The impact of PET/CT on therapeutic strategy of patients with colorectal cancer
      metastasis.
AB  - BACKGROUND/AIMS: The study's aim was to assess the impact of the PET/CT on the
      therapeutic strategy of the patients with colorectal cancer metastasis.
      METHODOLOGY: Fifteen patients who were suspicious of postoperative colorectal
      cancer metastasis were included in the study. Each patient received a positron
      emission tomography/computed tomography (PET/CT) after received contrast-enhanced
      computed tomography (ceCT). The therapeutic strategies were made before and after
      the PET/ CT respectively. The lesions confirmed by pathology or periodic follow
      up of ceCT (3 and 6 mo). RESULTS: Intrahepatic metastases were present in 5 of
      the 15 patients, total 9 lesions. The specificities of the PET/CT and ceCT were
      100%. The patients with intrahepatic metastases were detected by PET/CT and ceCT
      with a sensitivity of 100% and 80%, respectively (p = 0.0009). Extrahepatic
      metastases were present in 11 of the 15 patients, total 32 lesions. The
      specificities of the PET/CT and ceCT were 75% and 50%, respectively. PET/ CT and
      ceCT were with a sensitivity of 100% and 63.6%, respectively (p = 0.0177). The
      therapeutic strategies were changed after received PET/CT in 6 (40%) of the 15
      patients. CONCLUSIONS: PET/CT is superior to ceCT for the detection of the
      metastatic lesions of the colorectal cancer, and is a valuable tool to help
      select the correct therapeutic strategies.

PMID- 19760923
TI  - Refractory response to growth factors impairs liver regeneration after
      hepatectomy in patients with viral hepatitis.
AB  - BACKGROUND/AIMS: Liver regeneration after surgical resection is important. The
      present study was designed to understand the effect of background liver damage on
      the rate of liver tissue regeneration after hepatectomy and the mechanism of any
      defective regeneration. METHODOLOGY: The subjects were 40 patients who underwent
      liver resection. They comprised 22 patients with chronic viral hepatitis
      hepatocellular carcinoma (liver damage group) and 18 patients with hepatic
      metastases from colorectal cancer (normal liver group). Liver regeneration was
      evaluated by histopathological and immunohistochemical examination of the
      surgically resected tissue and by CT-scanning of the regenerated liver mass. The
      resected liver specimens were stained for c-met, gp-130 and nuclear factor-kappaB
      (NF-kappaB) proteins. RESULTS: Liver regeneration was significantly less in the
      liver-damage group than in the normal-liver group. Histopathological examination
      showed marked inflammatory cell infiltration in the liver-damage group.
      Expression of c-met, but not gp-130, was significantly higher on parenchymal
      cells of the liver-damage group than the normal-liver group. NF-kappaB expression
      in parenchymal liver cells was significantly higher than in non-parenchymal cells
      of the normal-liver group. In the liver-damage group, liver regeneration
      correlated negatively with the staining intensity of NF-kappaB protein in non
      parenchymal cells. These findings suggest that non-parenchymal cells are
      constitutively activated in the damaged liver, probably explaining the
      refractoriness of hepatocytes to cytokine-induced proliferation after
      hepatectomy, in spite of increased receptor (c-met) expression. CONCLUSIONS: The
      refractory response of injured hepatocytes to cytokines may explain the impaired
      postoperative liver regeneration in patients with damaged liver.

PMID- 19760924
TI  - The usefulness of endoscopic transpapillary procedure in post-cholecystectomy
      bile duct stricture and post-cholecystectomy bile leakage.
AB  - This study was conducted to examine the usefulness of endoscopic transpapillary
      procedure in post-cholecystectomy bile duct stricture and postcholecystectomy
      bile leakage. Endoscopic transpapillary procedure was performed in 18 cases of
      post-cholecystectomy bile duct stricture and 6 cases of post-cholecystectomy bile
      leakage. In the bile duct stricture cases, the patients were assessed for the
      stricture by endoscopic retrograde cholangiography (ERC), and then underwent
      endoscopic sphincterotomy (EST) for tube stent insertion. The stents was replaced
      every 3 to 6 months, and the treatment was continued until the patients became
      stent-free. Successful therapy was defined as a stent-free condition without
      hepatic disorder. In the bile leakage cases, the leakage was located by ERC and
      EST was performed. Then, endoscopic nasobiliary drainage (ENBD) tube was inserted
      at the proximal side of the bile leakage, and the therapeutic outcome was defined
      as successful if disappearance of the leakage was confirmed by cholangiography at
      a later date. Endoscopic transpapillary procedure was 100% successful in both
      post-cholecystectomy bile duct stricture cases (18/18) and post-cholecystectomy
      bile leakage cases (6/6). There was no accident due to the treatment. Restricture
      occurred in 5.5% (1/18) of the patients, but additional therapy was successful
      and the stent was removed. Also, there was no accident due to endoscopic
      transpapillary procedure. Endoscopic transpapillary procedure in
      postcholecystectomy bile duct stricture and postcholecystectomy bile leakage was
      demonstrated to be a less invasive, safe, and useful method.

PMID- 19760925
TI  - Clinicopathological features of signet-ring cell carcinoma of the colon and
      rectum: a case-matched study.
AB  - BACKGROUND/AIMS: Primary colorectal signet-ring cell carcinoma (SRC) is a rare
      type of mucin-containing adenocarcinoma and little information exists about its
      clinicopathological features. METHODS: The clinicopathological features of 27
      patients with primary colorectal SRC were compared with non-signet-ring cell
      mucinous carcinoma (MC) and non-mucinous adenocarcinoma (NMC). To analyze
      survival and recurrence, we used matched control groups. RESULTS: The mean age of
      patients in SRC was significantly younger than that of NMC (p = 0.003). The ratio
      of metastatic lymph nodes to harvested lymph nodes was also significantly higher
      in SRC (48.5 +/- 30.6) than in either MC (29.8 +/- 26.3; p = 0.009) or NMC (22.0
      +/- 21.6; p = 0.003). In stage II and III, SRC was found to be associated with a
      worse cancer-specific survival and a higher systemic recurrence rates than either
      NMC or MC. CONCLUSIONS: Primary colorectal SRC has distinctive
      clinicopathological features and is associated with a poorer prognosis than the
      other histological subtypes.

PMID- 19760926
TI  - A comparative study of two methods of colonic cleansing before colonoscopy.
AB  - BACKGROUND/AIMS: good colonic preparation is essential to perform a complete and
      safe colonoscopy. The preparation used in the Endoscopy Unit was adopted after
      testing it against the classic 4-liter polyethylene glicol (PEG) preparation
      (Klean-Prep). Recently a new 3-liter PEG preparation was commercialised in
      Portugal, Endo-Falk, which appeared to be simpler and effective. The present
      study compared the preparation we usually use (a combination of 4 tablets of
      bisacodyl with 2-liter PEG and enemas) with this new preparation. METHODOLOGY: we
      enrolled 305 patients in 2 groups. Group 1 was given our usual preparation, as
      described above and group 2 was given the new 3-liter preparation, Endo-Falk. All
      patients were ambulatory, and only patients undergoing total colonoscopies were
      included. Patients with benign or malignant stenosis and patients who had
      previously undergone colorectal resection were excluded. Preparation was graded
      as good when there were no stools and little liquid in the colon, fair when there
      were stools or liquid that could be aspirated and did not obscure the mucosa and
      bad when stools or excess liquid prevented an adequate view of the surface or
      precluded polipectomy. RESULTS: The present study included 164 male and 141
      female patients, with a mean age of 61.3 years (no difference between the
      demographic data). In group 1 the preparation was good in 57.5%, fair in 28.5%
      and bad in 14% of patients and in group 2 the preparation was good in 33.1%, fair
      in 48.9% and bad in 18% (p < 0.001). Colonoscopies were complete in 89.9% of all
      patients. CONCLUSIONS: The usual preparation was better than the new 3-liter PEG
      solution.

PMID- 19760927
TI  - The efficacy of prophylactic administration of SBT/ABPC for preventing surgical
      site infection in elderly patients undergoing colorectal surgery.
AB  - BACKGROUND/AIMS: Colorectal surgery presents a high risk of surgical site
      infections (SSI). SSI and prolonged hospital stay were associated with being aged
      75 yrs or older. The present study investigated the efficacy of sulbactam
      sodium/ampicillin sodium (SBT/ABPC), which is a combination drug of ampicillin
      and beta-lactamase inhibitor, as a prophylactic drug against SSI in elderly
      patient underwent colorectal surgery. METHODOLOGY: From July 2003 to November
      2005, a total of 181 patients underwent colorectal surgery. Of these patients, 43
      older than 75 yrs were compared with 138 who were younger. Patients were given
      SBT/ABPC as follows: Before anesthetic induction at surgery, 1.5 g of SBT/ABPC
      was administrated by intravenous drip infusion, and further doses were continued
      at 12-hour intervals for 2 days. We assessed SSI, postoperative stay, type of
      surgery, duration of operation, and amount of bleeding. RESULTS: The result was
      that SSI was found in none of the patients. There was no significant difference
      in rate of SSI and postoperative hospital stay between the two groups. Adverse
      reactions due to SBT/ABPC such as apparent skin symptoms or gastrointestinal
      symptoms were not observed. CONCLUSION: SBT/ABPC for elderly patients would be
      effective to prevent SSI in colorectal operations and could be used safely.

PMID- 19760928
TI  - CD133 gene overexpression is frequently observed in early colorectal carcinoma.
AB  - BACKGROUND/AIMS: Recently, it has been proved that colorectal carcinoma is
      created and propagated by a small number of undifferentiated tumorigenic CD133+
      cells. The present study examined the CD133 gene expression in colorectal
      carcinomas we surgically removed. METHODOLOGY: The CD133 gene expression in
      primary tumors and corresponding normal tissues derived from 30 patients with
      colorectal carcinoma was examined using a quantitative reverse-transcription PCR
      (QRT-PCR) and evaluated the correlation between the CD133 gene expression levels
      and the clinicopathological findings. RESULTS: An increase in CD133 expression
      scores was observed in Dukes A's colorectal carcinomas (1.70 +/- 2.28) compared
      to Dukes B and C's colorectal carcinomas (0.76 +/- 0.71) (p = 0.0860). An
      increase in CD133 expression scores was also observed in female colorectal
      carcinomas (1.29 +/- 1.56) compared to male colorectal carcinomas (0.61 +/- 0.57)
      (p = 0.125). CONCLUSIONS: CD133 gene overexpression in early colorectal cancer
      patients was more frequently observed than in advanced cases.

PMID- 19760929
TI  - Open colectomy versus laparoscopic-assisted colectomy supported by hand-assisted
      laparoscopic colectomy for resectable colorectal cancer: a comparative study with
      minimum follow-up of three years.
AB  - BACKGROUND/AIMS: Although laparoscopic colorectal cancer surgery is not widely
      used for several reasons especially for concerning inadequate resection, recent
      data showed equivalent oncologic outcomes between open colectomy (OC) and
      laparoscopic-assisted colectomy (LAC). However, there is no clinical trial for
      the LAC supported by hand-assisted laparoscopic colectomy (HALC), named as
      LAC/HALC. METHODOLOGY: Patients were assigned to either OC or LAC/HALC group.
      Clinical data, operation times, conversion rates from LAC to HALC, complications,
      early results, and long-term results were analyzed retrospectively. RESULTS: The
      short-term outcomes including pain, ambulation, oral resumption, wound
      infections, and hospital stays were favorable for LAC/HALC group. HALC was
      subsequently required in seven LAC cases but none of them required open
      colectomies. Functional recovery was the benchmark for early discharge for
      LAC/HALC group. Specimen size and number of lymph nodes harvested were similar.
      Local recurrence, disease-free and overall survival rates were comparable.
      CONCLUSION: The current study demonstrated that LAC/HALC was associated with
      favorable recoveries even in oncologic clearance in the long-term follow-up. HALC
      reduces the conversion rate from LAC to OC and maintains the benefits of minimal
      invasive surgery. Therefore, we suggest LAC/HALC is a suitable surgical hybrid
      for the treatment of resectable colorectal cancers.

PMID- 19760930
TI  - WNT5A gene is aberrantly methylated from the early stages of colorectal cancers.
AB  - BACKGROUND/AIMS: Recently, it has been reported that WNT5A methylation was
      frequently detected in colorectal cancers. However, the relationship between the
      WNT5A methylation and the characteristics of these cancers remains unknown.
      METHODOLOGY: Methylation status of the WNT5A gene was examined in primary
      carcinomas and the corresponding normal tissues derived from 49 patients with
      colorectal cancer using quantitative methylation-specific PCR (qMSP) and the
      correlation between the methylation status and the clinicopathological findings
      was evaluated. RESULTS: Aberrant methylation of the WNT5A gene was detected in 17
      out of the 49 (35%) primary colorectal cancers. The clinicopathological data were
      correlated with the methylation results. All stages of colorectal cancers
      presented WNT5A methylation. CONCLUSIONS: WNT5A gene has been methylated from the
      early stages of colorectal cancers.

PMID- 19760931
TI  - Conventional haemorrhoidectomy, stapled haemorrhoidectomy, Doppler guided
      haemorrhoidectomy artery ligation; post operative pain and anorectal manometric
      assessment.
AB  - BACKGROUND/AIMS: The aim of the present article was to compare stapled
      haemorrhoidectomy, and haemorrhoidal artery ligation with open haemorrhoidectomy
      with respect to the postoperative pain, symptom control, and manometric
      alterations. METHODOLOGY: Forty five patients with third or fourth-degree
      haemorrhoids were randomly classified into three groups; first group managed by
      stapled haemorrhoidectomy, second group managed by conventional haemorrhoidectomy
      and third group managed by Doppler guided haemorrhoidal artery ligation. (15
      patients each) Preoperative and 12 weeks postoperative anorectal manometry were
      done for all patients. RESULTS: There was a significant difference of the
      operative time between stapled group and Milligan-Morgan group (p < 0.001) while
      no significant difference between stapled group and Doppler group. The pain
      scores were significantly higher in open group (p < 0.001) during the first 24
      hours at the time of first motion and one week after operation. Postoperative
      control of prolapsed symptoms was significantly better with open diathermy
      haemorrhoidectomy than with stapled. The control of other symptoms was similar
      with regard to bleeding, pain, pruritus, and incontinence scores. Anorectal
      manometry showed a decrease in the maximum resting pressure and maximum squeeze
      pressure in all groups, but this decrease was only significant in the stapled
      haemorrhoidectomy group. CONCLUSIONS: Stapled and Doppler haemorrhoidectomy is as
      effective as conventional haemorrhoidectomy for the treatment of haemorrhoids,
      but with the exception of skin tag prolapse. There is a need for long-term follow
      up for the changes in manometric parameters after haemorrhoidectomy.

PMID- 19760932
TI  - Serial changes of cytokines in active ulcerative colitis: effects of antibiotic
      combination therapy.
AB  - BACKGROUND/AIMS: Although cytokines have an important role on the pathogenesis of
      ulcerative colitis (UC), the serial changes of cytokines have not been well
      characterized. It was examined cytokine levels in UC patients before and after
      administration of antibiotic combination therapy. METHODS: Protocol 1: A total of
      26 patients with active UC (13 treatment group, 13 control group) with a median
      age of 40.5 years were enrolled. Patients were randomly assigned to receive
      amoxicillin, tetracycline, and metronidazole per os for 2 wks (treatment group)
      or placebo (control group). Lichtiger's symptom score was determined before, 1
      month after, and 3 months after treatment, and Matts endoscopic score was
      determined before and 3 months after treatment. Protocol 2: A total of 23
      patients with active UC were enrolled (13 men, 10 women; mean age, 34.8 years).
      Serum levels of 17 cytokines were simultaneously determined using a Bio-Plex
      suspension array system (Bio-Rad Laboratories, Inc.) before, 1 month after, and 3
      months after treatment. RESULTS: Protocol 1: The incidence of clinical symptoms
      in the treatment group was significantly lower at 3 months after treatment
      compared to that before treatment and that in the control group (p < 0.05). The
      rate of change in endoscopic scores in the treatment group at 3 months after
      treatment was significantly decreased compared to that before treatment. Serum
      CRP in the treatment group at 1 month and 3 months after treatment was
      significantly decreased compared to before treatment. Protocol 2: There were no
      significant differences in the serum levels of the 17 cytokines before versus 1
      month or 3 months after treatment. However, IL-6 and MCP-1 levels tended to be
      lower 1 month after treatment compared to before treatment. Additionally, there
      was a significant correlation between the symptom score severity and serum IL-8
      and MIP-1beta levels. CONCLUSION: The present study results suggest that changes
      in IL-8 and MIP-1beta levels in UC treated with the antibiotic combination
      therapy may be associated with symptom relief.

PMID- 19760933
TI  - Minilaparotomy with a gasless laparoscopic-assisted procedure by abdominal wall
      lifting for ileorectal anastomosis in patients with slow transit constipation.
AB  - Total colectomy with ileorectal anastomosis (IRA) is the most widely adopted
      procedure. The aim of this study was to introduce a minimally invasive procedure,
      i.e., minilaparotomy with laparoscopic-assisted procedure, by abdominal wall
      lifting for IRA in patients with slow transit constipation (STC). Six STC
      patients (6 women, aged 40-69 years, mean age 56.3 years) underwent
      minilaparotomy with gasless laparoscopic-assisted approach by abdominal wall
      lifting for IRA. The present procedure involved a 7-cm lower abdominal median
      incision made at the beginning of the operation. 12 mm ports were also placed in
      the right and left upper abdominal quadrant positions. The upper abdominal wall
      was lifted by a subcutaneous Kirshner wire. The small wound was pulled upward
      and/or laterally by retractors (abdominal lifting) and conventional surgical
      instruments were used through the wound. Occasionally laparoscopic assistance was
      employed. The terminal ileum with total colon was brought out through the small
      wound and transected, approximately 5 cm from the ileocecal valve. The colon was
      also resected at the level of promontrium. Then, IRA was performed in the
      instruments. The total surgical time was 197.7 +/- 33.9 min and the mean
      estimated blood loss was 176.8 +/- 42.2 ml. There was no surgical mortality. Post
      operative hospitalization was 8.1 +/- 2.1 days. Six months after surgery, they
      defecated 1.8 +/- 2.1 times daily, have no abdominal distension, pain, and
      incontinence. The patients also take no laxatives. All subjects were satisfied
      with this procedure. Minilaparotomy with gasless laparoscopic-assisted IRA by
      abdominal wall lifting could be a safe and efficient technique in the treatment
      of STC.

PMID- 19760934
TI  - Pelvic peritonization after laparoscopic abdominoperineal resection for low
      rectal carcinoma treatment: surgical technique.
AB  - Abdominoperineal resection is a standard method of low-rectum carcinoma
      treatment. It is associated with significant morbidity and mortality rates, which
      decreased with the development of preoperative diagnostic procedures, new
      surgical techniques and new surgical instruments. In this article, laparoscopic
      pelvic peritonization was used after laparoscopic rectum amputation for low
      rectum carcinoma treatment. Pelvic peritonization is performed after laparoscopic
      recto-sigmoid extirpation, using the extended absorbable intracorporeal suture
      with titanic clip application after every second suture. The role of titanic clip
      is to grasp the extended suture and to mark the postoperative irradiation field.
      Laparoscopic pelvic peritonization after laparoscopic abdominoperineal rectum
      amputation is a simple procedure with clinical importance in possible adhesion
      and postirradiatic enteritis prevention. This procedure can satisfy all
      oncological requirements and minimally invasive surgery principles and is
      acceptable for every patient in which rectum amputation is indicated.

PMID- 19760935
TI  - Clinical characteristics of gastroesophageal reflux disease in Japan.
AB  - BACKGROUND/AIMS: Little is known about the correlation between clinical symptoms
      in daily life and the endoscopic features of gastroesophageal reflux disease
      (GERD). The study aim is to evaluate the correlation between clinical symptoms in
      daily life and endoscopic findings in reflux esophagitis (RE), and endoscopically
      suspected esophageal metaplasia (ESEM) in a large number of Japanese non-clinical
      cases. METHODOLOGY: A total of 6504 subjects who underwent an endoscopy for their
      annual medical check-up at Miyagi cancer society were enrolled in this study. If
      esophagitis was present, it was graded according to the Los Angeles
      classification. ESEM describes endoscopic findings consistent with BE that await
      histological evaluation. It was also investigated the symptom of heartburn as a
      "typical symptom" of GERD, and dysphagia as an "atypical symptom" of GERD.
      RESULTS: The prevalence of heartburn and dysphagia significantly increased
      concomitantly with endoscopic the esophagitis grading. The prevalence of
      heartburn was significantly higher in subjects with long segment ESEM than those
      without it. CONCLUSION: The prevalence of heartburn and dysphagia were closely
      associated with RE grading. Long segment ESEM is strongly associated with the
      reflux symptom and RE. The more frequent the GERD symptoms, the greater the risk
      for the development of severe RE, and ESEM.

PMID- 19760936
TI  - Video-assisted laparoscopic resection of the esophagus for carcinoma after
      neoadjuvant therapy.
AB  - BACKGROUND/AIMS: Classical operation approaches, used for decades during subtotal
      esophageal resection for esophageal carcinoma, have certain disadvantages. The
      transhiatal "blind" approach according to Orringer lacks sufficient radicality,
      the thoracotomic approach is burdened by serious postoperative complications,
      primarily respiratory. These disadvantages are eliminated to a great extent by
      use of the video-assisted laparoscopic transhiatal approach, which is presented
      in our study. METHODOLOGY: Between 2000-2006 forty-three patients with esophageal
      cancer underwent video-laparoscopic transhiatal esophagectomy. In all patients
      passage was renewed by esophagogastroplasty, constructed by placing the
      neoesophagus in the posterior mediastinum, anastomosis with the cervical
      esophagus from a laparotomy. Prior to the operation, 27 patients underwent
      neoadjuvant radio-chemotherapy. Chemotherapy consisted of 5 fluorouracil and
      cisplatinum, and radiotherapy with a total dose of 50 Gy. RESULTS: The
      extirpation phase was completed laparoscopically in all patients. Right-sided
      pneumothorax was seen in 27 patients, in six cases postoperative manifestation of
      left vocal chord paresis due to damage to the recurrent laryngeal nerve was
      observed, in 2 patients a fistula developed in the cervical anastomosis, which in
      all cases healed spontaneously. The operation time ranged between 225-370
      minutes, the average time being 256 minutes. The mini-invasive phase took an
      average of 40 minutes. One patient died 57 days after the operation due to
      respiratory insufficiency. The average hospital stay was 12.2 days. CONCLUSIONS:
      The video-assisted laparoscopic transhiatal approach proved to be very useful
      during subtotal esophageal resection. In tumors localized in the lower portion of
      the esophagus, it completely replaces the transhiatal "blind" approach according
      to Orringer and, in comparison, eliminates operative hemorrhagic complications,
      which are more frequent in "blind" extirpations, especially in patients after
      neoadjuvant therapy. It also enables performing a lymphadenectomy, which is not
      possible using the "blind" approach. In tumors of the middle thoracic esophagus,
      which are inaccessible by the original Orringer's approach, it eliminates the
      need for a thoracotomy, which significantly contributes to the decrease of
      respiratory complications.

PMID- 19760937
TI  - Impact of lymph node involvement in T2 or T3 thoracic esophageal squamous cell
      carcinoma.
AB  - BACKGROUND/AIMS: Treatment strategy for T2/ T3 esophageal carcinoma has become
      controversial because of recent improvements in chemoradiation therapy. Only a
      few study analyzed the prognostic impact of clinicopathological factors for
      surgical outcome of patients with esophageal carcinoma focused on T2/T3 tumors.
      METHODOLOGY: Subjects of this study were 187 patients with pathological T2 (n =
      46) or pathological T3 (n = 141) thoracic esophageal squamous cell carcinoma who
      received surgical treatment without neoadjuvant therapy. The impact of
      clinicopathological factors on survival was evaluated by univariate and
      multivariate analysis. RESULTS: Overall 5-year survival rate of all patients was
      38%. Dismal 5-year overall survival rates were observed in patients with 5 or
      more positive nodes (11%). Multivariate analysis indicated that lymph node
      metastases (hazard ratio; 2.07, 95%IC, 1.20-3.56, p < 0.01) and the number of
      metastatic nodes (hazard ratio; 1.77, 95%IC, 1.11-2.82, p = 0.02) were
      independent risk factors for poor survival. However, tumor depth itself was not
      an independent risk factor for survival. CONCLUSIONS: Although survival of
      patients with pathological T2 or T3 was partly dependent on tumor depth, it was
      mainly dependent on lymph node status. Multiple positive nodes were independent
      risk factors for poor survival.

PMID- 19760938
TI  - Relationship between nutritional therapy and surgery in Crohn's disease.
AB  - BACKGROUND/AIMS: Crohn's disease is often refractory and some patients require
      repeated surgical treatment. Nutritional therapy with an elemental diet has been
      reported effective in improving nutritional state and suppressing inflammation,
      and might be expected to assist in minimizing the need for surgery. We evaluated
      the relationship between an elemental diet and the period that patients spent
      without intestinal resection. METHODOLOGY: A total of 153 patients with Crohn's
      disease who visited our hospital from July, 1999 to July, 2005 were enrolled. The
      relationship between the caloric content of an elemental diet and surgery as an
      endpoint was examined using Cox regression analysis. Cumulative non-operation
      rates were calculated by the Kaplan-Meier method. Statistical significance was
      determined using the log-rank test. RESULTS: Among patients with jejunoileal
      involvement, patients receiving an elemental diet providing 900 kcal or more per
      day showed a statistically significant improvement in cumulative non-operation
      rate. Among those without jejunoileal involvement, in contrast, the cumulative
      non-operation rate did not differ among those receiving an elemental diet of less
      or more than 900 kcal per day. CONCLUSIONS: The use of an elemental diet of 900
      kcal per day may be effective in avoiding surgery in patients with jejunoileal
      lesions. This diet may be useful in improving long-term convalescence in these
      patients.

PMID- 19760939
TI  - Factors affecting postoperative dietary adaptation in short bowel syndrome.
AB  - BACKGROUND/AIMS: To investigate factors that affect post-operative dietary
      adaptation in patients with short bowel syndrome. METHODOLOGY: It was reviewed
      post-operative nutritional courses in nine patients with less than 200cm of
      residual small bowel after bowel resection. Surgical factors affecting post
      operative dietary adaptation were analysed in view of the post-operative weaning
      from parenteral nutrition (PN). RESULTS: One of two patients with less than 50 cm
      of residual small bowel achieved oral feeding. This patient with 40 cm of
      residual small intestine, who had undergone small bowel resection 12 months
      previously, achieved oral feeding within one month. As a whole, only 2 patients
      failed to wean PN. One patient with 40 cm of residual small intestine, who had
      undergone total gastrectomy three months ago, failed to wean PN. The other
      patient with 160 cm of ileum without the stomach, duodenum, jejunum, ileocecal
      valve, or most of the colon after three consecutive bowel resections, failed to
      wean PN. CONCLUSIONS: Tapering of PN was possible even in patients with less than
      50 cm of residual small bowel, if they had undergone previous bowel resections
      and were provided with adequate PN for a sufficient time.

PMID- 19760940
TI  - Detection of gastrointestinal and abdominal infections by 99mTc-antigranulocyte
      antibodies.
AB  - BACKGROUND/AIMS: The aim of the study was detection of abdominal infections by
      99mTc- antigranulocyte antibodies. METHODOLOGY: Total of 36 patients with
      clinical suspicion on abdominal or gastrointestinal infections was investigated.
      RESULTS: There were 23 true positive (TP) findings (one pulmonary abscess, 2
      subhepatic abscesses after surgery, 2 perianal fistula, 2 chronic and 4 acute
      appendicitis, 5 abdominal and 3 pelvic abscesses, 3 M. Crohn, one ulcerative
      colitis), 9 true negative (TN) (3 tumors of the coecum, 2 tumors of papilla
      Wateri, 2 gastric carcinoma, 2 colon carcinoma), and 4 false negative (FN) (2
      abscesses subphrenic and 2 enterocolic fistula). False positive (FP) findings
      were not observed. The smallest lesion found was 19x18 mm. SPECT increased the
      number of TP findings from 17 to 23. Fifteen of 23 infectious of inflammatory
      lesions could be detected in the early scan. Sensitivity was 85%, specificity
      100%, positive predictive value 100%, negative predictive value 69% and accuracy
      89%. CONCLUSION: According to the present results, scintigraphy with 99mTc
      antigranulocyte antibodies is a useful method for detection and assessment of
      exact localization abdominal infections, which is very important for the prompt
      and appropriate therapy.

PMID- 19760941
TI  - Are proton pump inhibitors really superior to famotidine in Japanese ulcer
      patients?
AB  - BACKGROUND/AIMS: The study aim was to evaluate the efficacy of famotidine in
      Japanese patients with peptic ulcers; it was analyzed the pooled data from
      previously conducted clinical trials in Japan. METHODOLOGY: In the present study
      was performed a meta-analysis of controlled trials of famotidine and proton pump
      inhibitors executed between 1985 to 2005. The patients included in this study
      were Japanese adults (> or = 19 years old) diagnosed with gastrointestinal
      ulcers, treated for an on-label indication at doses approved in Japan, and whose
      treatment outcomes were clearly shown. It was searched the JMEDPlus database for
      relevant data. Data were synthesized and the results expressed as relative risk
      (RR). RESULTS: Of the nine articles analyzed with a total of 1,771 patients, 879
      received famotidine, and 892 received proton pump inhibitors. For duodenal ulcer
      and the hemostatic effect on the upper gastrointestinal tract, there were no
      significant differences between the two groups (p = 0.064, p = 0.066,
      respectively), although proton pump inhibitors showed a significantly greater
      efficacy compared to famotidine for gastric ulcers (RR: 0.86 [95% CI: 0.78-0.93],
      p < 0.001). CONCLUSIONS: In Japanese patients, there were no significant
      differences for duodenal ulcer and hemostatic effect on the upper
      gastrointestinal tract between famotidine and proton pump inhibitors.

PMID- 19760942
TI  - Regeneration of peritoneum using amniotic membrane to prevent postoperative
      adhesions.
AB  - BACKGROUND/AIMS: Adhesions following intraperitoneal surgery are frequent causes
      of small bowel obstruction. Attempts to prevent postoperative adhesions have
      mostly proven disappointing clinically. Currently used by ophthalmologists in
      ocular surface disorders, amniotic membrane transplantation can reduce
      inflammation and promote re-epithelization. We used amniotic membrane for
      facilitating peritoneal regeneration and prevention of adhesions with surgical
      trauma. METHODOLOGY: 20 rats were randomized in equal number into treatment or
      control groups. Seven days after operation, the incidence and severity of
      adhesions were evaluated. Histologic and immunohistochemical analyses were
      examined at 1, 4, 10 weeks after operation. RESULTS: While severe adhesions were
      observed after 1 week between the cecum and surrounding organs in the control
      group, adhesion formation was significantly reduced in the amniotic membrane
      group. Histologic examination demonstrated that free-floating myofibroblasts in
      the peritoneal cavity attached to surfaces of amniotic membrane grafts to form a
      layered structure. Free-floating mesothelial cells were incorporated into the
      regenerating mesothelium on the myofibroblast layer in 4 weeks, while implanted
      amniotic membrane grafts were absorbed by 10 weeks. In the amniotic membrane
      group the cecum appeared nearly normal. CONCLUSIONS: Amniotic membrane grafts
      reduced intraperitoneal adhesions after surgical trauma, were well absorbed, and
      served as a substrate for regenerating mesothelium.

PMID- 19760943
TI  - Small bowel alterations in portal hypertension: a capsule endoscopic study.
AB  - BACKGROUND/AIMS: The endoscopic appearance in portal hypertension is well
      described in the stomach and the colon, but there is a limited number of data
      available on small bowel changes. The present retrospective, comparative study
      was aimed to analyse the diagnostic yield and describe the small bowel findings
      with capsule endoscopy in cirrhotic patients with gastrointestinal bleeding of
      unknown origin. METHODOLOGY: Capsule endoscopy findings of 11 cirrhotic patients
      with portal hypertension and 22 non-cirrhotic patients with gastrointestinal
      bleeding who had undergone non-diagnostic upper endoscopy and colonoscopy, which
      were then compared. RESULTS: In total, 9A and 2B cirrhotic patients were examined
      based on Child-Pugh score with a mean age of 66.2 (+/- 7.6) years. Lesions
      originated to portal hypertension were found in all cirrhotic patients, most
      frequently multiple angiodysplasias (63.6%), while in the control group multiple
      angiodysplasias were a seldom finding (18.2%). None of the radiological and
      endoscopic examinations of the small bowel before capsule endoscopy showed
      positive findings in cirrhotic patients. CONCLUSION: Capsule endoscopy is an
      effective diagnostic method with high diagnostic yield in portal hypertension.
      Multiple angiodysplasias are the most probable findings as the source of small
      bowel bleeding in these patients.

PMID- 19760944
TI  - Implantation of a Denver shunt by left subclavian approach for preventing
      kinking.
AB  - Ascites often contributes to patient morbidity and discomfort. Implantation of a
      Denver peritoneovenous shunt is one of the treatments for refractory ascites.
      However, the dysfunction of the shunt is frequently observed and requires further
      improvement. Here, the present paper reported the improved implantation technique
      for the Denver peritoneovenous shunt. All the procedures were performed in the
      operating suite under general anesthesia. In all patients, the shunts were
      percutaneously placed via the left subclavian vein approach under digital
      fluoroscopic guide along with ultrasound. Fourteen shunts were implanted in 14
      patients with hepatic failure-related ascites. The shunt was successfully
      positioned in all patients in an average time of 45 min without the kinking. No
      complications directly related to the procedure occurred. The Denver
      peritoneovenous shunt is useful in resolution of refractory ascites, as it
      reduces symptoms, and allows effective palliation. Implantation of the Denver
      peritoneovenous shunt via left subclavian vein approach is a relatively easy,
      rapid, and secure procedure that prevents kinking.

PMID- 19760945
TI  - Laparoscopy-assisted ileocecal resection for mucosa-associated lymphoid tissue
      lymphoma of the appendix: case report.
AB  - A 74-year-old female had repeated relapses of right lower abdominal pain; a
      colonoscopic examination showed a submucosal tumor of the appendix. Under
      provisional diagnosis of appendicitis caused by a submucosal tumor, a
      laparoscopic operation was performed. The laparoscopic observation did not reveal
      the typical finding of appendicitis. The tumor was thought to be a malignant
      neoplasm. The ileocecal region was excised with lymph node dissection.
      Macroscopically, the mass was localized in the appendix and did not infiltrate to
      the cecum. Histologically, the marginal zone consisted of lymphoid cells, and
      centrocyte-like cells were observed. Immunohistochemically, the tumor cells were
      positive for CD20 and CD79a and negative for CD3, CD10, and cyclin D1. The
      histological diagnosis was mucosa-associated lymphoid tissue (MALT) lymphoma of
      the appendix. Colonic MALT lymphoma is rare and rarely diagnosed before surgery.
      Furthermore, very few cases of the appendiceal MALT lymphoma have been reported.
      The laparoscopy was used in the case of a patient diagnosed with appendicitis and
      considered the possibility of MALT lymphoma of the appendix. We then performed an
      ileocecal resection, which is considered radical surgery. The present case
      suggests that a laparoscopic observation is helpful for the appropriate diagnosis
      and therapy of MALT lymphoma of the appendix.

PMID- 19760946
TI  - Laparoscopic liver resection for hepatocellular carcinoma: intermediate follow-up
      results.
AB  - BACKGROUND/AIMS: Laparoscopic hepatectomy (LH) has gained increased acceptance
      for the treatment of selected hepatocellular carcinoma (HCC). The technical
      consideration and long-term follow-up data of LH for hepatocellular carcinoma are
      limited. The current study presents the experience of 17 LH for HCC with a mean
      follow-up of 23 months. METHODOLOGY: From April 2003 to December 2005, we
      successfully performed 17 LH for patients with HCC. Patient demographics, peri
      operative parameters and outcomes of the 17 patients were assessed
      retrospectively. RESULTS: All 17 LH were performed smoothly without conversion to
      laparotomy. There was no operative mortality, but transfusion and relaparoscopy
      was required for one patient with internal bleeding 7 days after LH. The mean
      hospital stay was 10.9 (6-23) days. All but one patient had section margins
      longer than 1 centimeter. Four patients had tumor thrombi in portal vessels of
      their resected specimen. During the mean follow up of 23 months, five patients
      (29.4%) developed recurrence. Four of the recurrences limited in the liver, and
      one patient had both liver and lung metastasis. No port site or peritoneal
      metastases were observed. Treatment of recurrence was second resection in one
      patients and trans-arterial embolization therapy in four other patients. Mean
      disease-free survival was 19 months. CONCLUSIONS: Laparoscopic hepatectomy is
      feasible in selected patients with single, smaller and peripherally-located
      hepatocellular carcinoma. The surgical morbidity and intermediate followup
      results seem satisfactory.

PMID- 19760947
TI  - Specific characteristics of scirrhous hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: Scirrhous hepatocellular carcinoma has been defined within
      general hepatocellular carcinoma. To define scirrhous hepatocellular carcinoma,
      the present study identified the specific characteristics as compared with
      general hepatocellular carcinoma. METHODOLOGY: The scirrhous hepatocellular
      carcinoma was defined when almost all areas of the tumor were occupied with
      scirrhous structures. It was identified 14 patients with scirrhous hepatocellular
      carcinoma and 300 patients with general hepatocellular carcinoma (control), all
      underwent hepatectomy from 1988 to 1994. It was compared the clinical background
      of the patients, prognosis, and pathological features, which included
      immunohistological staining using Hepatocyte Paraffin 1. RESULTS: All scirrhous
      hepatocellular carcinoma showed whitish, hard forms resembling intrahepatic
      cholangiocarcinoma. The rates of average ICGR15, positive hepatitis C virus
      antibody, and microscopic invasion to the bile duct were 12%, 33%, and 20%,
      respectively, each significantly different than general hepatocellular carcinoma.
      The cumulative 10-year survival rate of scirrhous hepatocellular carcinoma and
      general hepatocellular carcinoma were 70% and 31%, respectively. With
      immunohistological staining, 43% of scirrhous hepatocellular carcinoma showed
      negative staining for Hepatocyte Paraffin 1. CONCLUSIONS: The scirrhous
      hepatocellular carcinoma has specific characteristics such as lower rates of
      hepatitis C virus infection, better prognosis, and different histological
      findings; therefore, scirrhous hepatocellular carcinoma should be strictly
      classified under a new category.

PMID- 19760948
TI  - Analysis of BCLC treatment indications. Have BCLC modified our choice of
      treatment in HCC patients? A retrospective study.
AB  - BACKGROUND/AIMS: The Barcelona Clinic Liver Cancer (BCLC) classification has been
      recently validated as the best system for treatment guidance for hepatocellular
      carcinoma (HCC), but it doesn't properly consider liver dysfunction. The aim of
      this retrospective study is to evaluate the usefulness of BCLC for hepatic
      surgeons comparing our treatment decision and BCLC algorithm indications.
      METHODOLOGY: A retrospective analysis of 102 patients affected by HCC observed
      from 1991 to 2002 was performed. The treatment choice was compared with the
      treatment schedule proposed by BCLC. RESULTS: Of 102 patients, in 44 (43.1%)
      cases, the present study treatment and BCLC system agreed, while in the remnant
      58 (56.9%) cases, there was an under treatment in 47 (81.1%) patients and an
      overtreatment in 11 (18.9%). About the undertreatment cases we didn't perform
      hepatic resection such as BCLC suggests because of advanced age and/or high level
      of IGC; in patients in whom BCLC would suggest chemoembolization, we supposed
      this treatment as high risk therapy. Regarding the overtreatment, we choose
      hepatic resection, because early Child B class and good liver functional status.
      CONCLUSIONS: Analysing our aprroach in the treatment of HCC during ten years
      before introduction of BCLC classification, we can conclude that even if our
      treatment choice disagreed with BCLC systems, this wouldn't changed our decision
      especially in surgical indications.

PMID- 19760949
TI  - Apoptosis is activated in an early period after radiofrequency ablation of liver
      tissue.
AB  - BACKGROUND/AIMS: Hyperthermia induced apoptosis may lead to tumor cell death thus
      expanding the volume of non-viable tissue and warrant a "safety margin" of at
      least 10mm to exclude the possibility of tumor recurrence. We carried out an
      experimental study to investigate the cellular injury produced by radiofrequency
      ablation in the area surrounding the ablated tissue and to describe early
      apoptotic processes in the transition zone following radiofrequency ablation
      procedure in a porcine liver model. METHODOLOGY: Nine anesthetized pigs underwent
      laparotomy and local thermal ablation of the liver parenchyma. The ablated tissue
      and the surrounding parenchyma were investigated for apoptosis applying Western
      blot analysis and immunohistochemistry. RESULTS: The active (cleaved) caspase-3
      17-kDa subunit was detected in the transition zone one hour after ablative
      procedure at a distance of 9-10 mm from the rim of the necrosis zone. In contrast
      analysis of tissues in necrosis zone and in surrounding normal liver parenchyma
      revealed no markers of apoptotic activity. CONCLUSION: We determined that
      apoptosis, leading to further cell death, is activated in the majority of cells
      in the transition zone, thus supporting the hypothesis that the "safety margin"
      of 10 mm is encompassed by the indirect thermal effect.

PMID- 19760950
TI  - Effect of an angiotensin-II type-1 receptor blocker, candesartan on hepatic
      fibrosis in chronic hepatitis C: a prospective study.
AB  - BACKGROUND/AIMS: Recent studies have shown that blocking of angiotensin-II
      signaling can attenuate liver fibrosis in various experimental models. The aim of
      this study was to examine the clinical effect of an angiotensin-II type-1
      receptor blocker, candesartan, on the progression of hepatic fibrosis in chronic
      hepatitis C patients. METHODOLOGY: Twelve chronic hepatitis C patients with
      hypertension enrolled as candesartan-treated patients and followed up
      prospectively, were compared with age- and sex-matched 20 chronic hepatitis C
      patients with no candesartan treatment. We evaluated alterations in hepatic
      fibrosis grades with these noninvasive fibrotic indexes: Forns index, the AST to
      platelet ratio index (APRI) and FibroIndex, every 3 months. RESULTS: There were
      initially no significant differences between the candesartan-treated and control
      groups in clinical characteristics. Candesartan treatment induced a significant
      improvement in Forns Index, APRI and FibroIndex during treatment in comparison
      with the control group. There were no severe side effects in the candesartan
      group. CONCLUSIONS: These results suggest that candesartan in regular doses has
      an anti-fibrotic effect on patients with chronic hepatitis C.

PMID- 19760951
TI  - Cytokine evaluation in liver cirrhosis and hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: The purpose of this study was to examine the roles of tumour
      necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, IL-18, and alpha
      fetoprotein (AFP) in patients with liver cirrhosis (LC) and hepatocellular
      carcinoma (HCC). METHODOLOGY: AFP and cytokine serum concentrations were
      determined via EIA or ELISA. RESULTS: In total, 81 patients were included,
      including 9 healthy controls, 36 LC patients, and 36 HCC patients. Significant
      differences in AFP, TNF-alpha, IL-6, and IL-18 between the three groups were
      noted (p < 0.001). AFP was lowest in the healthy subjects, intermediate in LC
      patients and highest in HCC patients (all p < 0.001). 11-6 and 11-18
      concentrations were significantly higher in the HCC group than the other two
      groups. HCC and LC patients with AFP concentration > 7ng/ml had increased IL-18
      concentrations compared to both the other groups p < 0.001). In contrast to
      previously published studies, TNF-alpha was highest in the healthy group,
      intermediate in the HCC group, and lowest in the LC group (p < 0.001).
      CONCLUSIONS: IL-18 may be a potential tumour marker in combination with IL-6 and
      AFP in the diagnosis of HCC, but further research including a larger population
      of patients is essential. Further research is warranted.

PMID- 19760952
TI  - The clinical value of 18F-FDG PET/CT for investigating unexplained serum AFP
      elevation following interventional therapy for hepatocellular carcinom.
AB  - BACKGROUND/AIMS: The goal of this study was to assess the clinical usefulness of
      18F-FDG PET/ CT for investigating unexplained serum AFP elevation following
      interventional therapy such as transarterial chemoembolization (TAE) or
      radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). METHODOLOGY: A
      retrospective study was conducted involving 18 HCC patients (9 men and 9 women;
      age, 42-67 years) who underwent 18F-FDG PET/CT for evaluation of AFP without
      evidence of HCC recurrence on multiphasic abdominal CT after TAE or RFA
      treatment. The results of the 18F-FDG PET/CT were compared with histological,
      radiological and clinical follow-up. RESULTS: Among 18 patients, 14 patients
      demonstrated HCC recurrence (10 intrahepatic, 3 extrahepatic and 1
      intrahepatic/extrahepatic). Metastatic foci were found in the lung (1 patient),
      bone (1 patient), lymph node (1 patient), and adrenal gland (1 patient). The 18F
      FDG PET/CT identified seven intrahepatic and four extrahepatic lesions. Overall,
      the 18F-FDG PET/CT had nine true-positives, five false-negatives, four true
      negatives and zero false-positives for the detection of HCC recurrence. The
      sensitivity, specificity and accuracy were 64%, 100% and 72%, respectively.
      CONCLUSIONS: When the multiphasic CT was normal, the 18F-FDG PET/CT was valuable
      to reveal intrahepatic tumor recurrence and/or extrahepatic metastases in
      patients with AFP elevation after interventional therapy for HCC.

PMID- 19760953
TI  - Effects of lovastatin and pentoxyphyllin in nonalcoholic steatohepatitis.
AB  - BACKGROUND/AIMS: Today, there is no ideal treatment for nonalcoholic
      steatohepatitis. The present study intended to make a multicentric prospective
      study about the efficiency of lovastatin and pentoxyphyllin administered in
      patients with nonalcoholic steatohepatitis. METHODOLOGY: 87 patients were
      included in the present study. The patients diagnosed with nonalcoholic
      steatohepatitis and dislypidemia were treated for 4 months with lovastatin 10
      mg/day and those without dislypidemia with pentoxyphyllin, 400 mg x 3/day. The
      patients were evaluated clinically and biochemically monthly. RESULTS: Regarding
      the lovastatin-treated group, transaminases significantly decreased (p < 0.05),
      after the first and second month, as well as cholesterolemia (p < 0.001), and the
      APRI score after 2 months (p = 0.03). In the pentoxyphyllin-treated group,
      transaminases significantly decreased after 1 month (p < 0.05), and the Forns
      index after 2 months (p < 0.05). CONCLUSIONS: Both drugs significantly decreased
      the transaminases. Lovastatin reduced the cholesterolemia in the dislipidemic
      patients. The decrease of the APRI score suggests that both medicines have
      benefic effects on the hepatic histology, too.

PMID- 19760954
TI  - High serum levels of vascular endothelial growth factor after hepatectomy are
      associated with poor prognosis in hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: Vascular endothelial growth factor (VEGF) reportedly affects the
      metastatic potential of tumors. We investigated in patients whether association
      exits between perioperative serum VEGF levels and recurrence of hepatocellular
      carcinoma (HCC). METHODOLOGY: Thirty-two patients who underwent curative
      resection for HCC were enrolled in this study. Blood samples were obtained at 6
      points during the perioperative period: preoperative day and, postoperative days
      1, 2, 3, 7 and 14). Serum VEGF levels were measured by enzyme-linked
      immunosorbent assay. We divided the 32 hepatocellular carcinoma patients into a
      high VEGF group (preoperative serum level > or = 100 pg/ ml, n = 10) and a low
      VEGF group (preoperative serum level < 100 pg/ml, n = 22). RESULTS: During a
      median follow-up period of 27.1 months, the cancer recurred in 20 of the 32
      patients. Disease-free survival in the high VEGF group was significantly poorer
      than that in the low VEGF group (p < 0.05). Serum VEGF levels in the high VEGF
      group remained significantly higher than those in the low VEGF group after
      hepatectomy (p < 0.05). Serum VEGF levels in the recurrent group were also
      significantly higher than those in the non recurrent group at preoperative day,
      postoperative days 2, 3 and 7 (p < 0.05). CONCLUSIONS: High serum VEGF levels
      during perioperative period may be a risk factor for intrahepatic recurrence
      after complete resection for HCC.

PMID- 19760955
TI  - Usefulness of radiofrequency ablation with micro-convex probe for hepatocellular
      carcinoma.
AB  - BACKGROUND/AIMS: It was aimed to assess whether a micro-convex probe is superior
      to the present conventional probe for ultrasonography from the points of safety
      and efficacy during percutaneous radiofrequency ablation therapy for
      hepatocellular carcinoma. METHODOLOGY: Twenty-one patients with 23 hepatocellular
      carcinoma lesions who had one or 2 lesions, each 4 cm or less in diameter, and
      liver function of Child-Pugh class A or B were enrolled. All the patients except
      for 2 patients were seropositive for hepatitis C virus. Radiofrequency ablation
      was carried out under a real-time US guidance. The cooled-tip electrodes used
      were single and clustered. RESULTS: It was possible to perform safe and accurate
      percutaneous radiofrequency ablation procedure using micro-convex probes for the
      treatment of all hepatocellular carcinoma nodules. It was also possible to treat
      hepatocellular carcinoma located in the right subphrenic region without
      artificial pleural effusion under intercostal ultrasonography guide. Improved
      clustered needles were successfully applied to treat the nodules more than 3 cm
      in diameter with less resistance for penetration compared with the conventional
      needle. The findings of advanced dynamic flow image on ultrasonography to assess
      the therapeutic efficacy indicated the consistency with those of dynamic CT which
      was done 3 to 5 days later radiofrequency ablation. Major complication of
      radiofrequency ablation procedure was noted in none. CONCLUSIONS: These results
      suggest that micro-convex probe with clustered tips is superior to conventional
      probe for ultrasonography from the points of safety and efficacy during
      radiofrequency ablation for hepatocellular carcinoma nodule located in the right
      subphrenic region and for larger sized nodule more than 3 cm.

PMID- 19760956
TI  - Effects of donor age on patient survival in liver transplantation: short-and long
      term analysis.
AB  - BACKGROUND/AIMS: This study aim was to investigate an association between donor
      age and lower recipient survival in liver transplantation. METHODOLOGY: A total
      of 178 consecutive patients underwent liver transplantation between 1999 and
      2007. Among these patients, 172 liver transplants (donor age: 32.04 +/- 16.66)
      and 167 recipients were included in the analysis. Mean recipient age was 39.16 +/
      21.61 years (range: 6 mo-71 years) and 90 (53.89%) were males. RESULTS: Among
      172 transplants, 32.9% recipients died during follow-up. Mean follow-up time was
      34.37 +/- 20.50 mo. A lower mean recipient survival prevailed from donors older
      than 50 years (p = .01) at 7-year patient survival. At 6-month and 1-year
      recipient survival, cut-offs were 50 and 55 years, respectively (p < .05). A
      significant difference was observed in graft survival from donors older than 30
      years (p = .02) and at 6-month and 1-year, cutoffs were 35 and 50 years,
      respectively (p < .05). CONCLUSIONS: Although the utilization of donors with
      increased age in liver transplantation offers a new option to increase the number
      of liver transplants it presents lower survivals. Other factors related to graft
      loss such as MELD score > 15 and longer CIT (cold ischemia time) should be
      avoided to reduce the risk of using elderly donor grafts.

PMID- 19760957
TI  - Evaluation of new prognostic staging systems (SLiDe score) for hepatocellular
      carcinoma patients who underwent hepatectomy.
AB  - BACKGROUND/AIMS: A new prognostic staging system, the SLiDe (S, stage; Li, liver
      damage; De, des-gamma-carboxy prothrombin) score was recently proposed. We
      examined 207 HCC patients following hepatic resection to determine the usefulness
      of this staging system for HCC patients after surgery. METHODOLOGY: Disease-free
      and overall survival rates were calculated according to the Kaplan-Meier method,
      and differences between groups were tested for significance using the log-rank
      test. RESULTS: Regarding disease-free survival, there were no significant
      differences in survival between SLiDe score 0 vs 1, between score 2 vs 3, and
      between score 4 vs 5. There were significant differences between 0-1 vs 2-3 (p <
      0.01) and between 2-3 vs 4-5 (p < 0.01). Regarding overall survival, there were
      no significant differences in survival between score 0 vs 1, between score 2 vs
      3, and between score 4 vs 5. There were significant differences between 0-1 vs 2
      3 (p < 0.05) and between 2-3 vs 4-5 (p < 0.01). CONCLUSIONS: The SLiDe score, a
      staging system that combines tumor factors, a tumor marker and hepatic function,
      might be a better predictor of prognosis in HCC patients who have undergone
      hepatic resection.

PMID- 19760958
TI  - Prevalences of viremic hepatitis C and viremic hepatitis B in pregnant women in
      Northern Norway.
AB  - BACKGROUND/AIMS: No data exist for current infections of hepatitis C and
      hepatitis B virus in pregnant women in Northern Norway. The aim of this study was
      to determine the prevalences of viremic hepatitis C and hepatitis B of pregnant
      women in Northern Norway. A cross-sectional, multi-center study with
      participation of all hospitals and delivery rooms in this region was performed.
      METHODOLOGY: All pregnant women who consecutively underwent ultrasound screening
      in 17th - 19th weeks of pregnancy during the period between October 2003 and
      October 2004 were invited to participate in the study. On the day of
      ultrasonography venous blood samples were collected for analysis of serum for
      antibody to hepatitis C virus, hepatitis C virus ribonucleicacid, recombinant
      immunoblot assay, hepatitis B surface antigen, antibody to hepatitis B surface
      antigen and antibody to hepatitis B core antigen. RESULTS: Out of 4087 eligible
      pregnant women 1668 (41%) were included in the study. The prevalences of viremic
      hepatitis C (hepatitis C virus ribonucleicacid positive) and viremic hepatitis B
      (hepatitis B surface antigen positive) were 0.2% (95% CI 0.0 - 0.5) and 0.1% (95%
      CI 0.0 - 0.3) respectively. CONCLUSIONS: The prevalences of viremic hepatitis C
      and hepatitis B in pregnancy in Northern Norway were low.

PMID- 19760959
TI  - Serum prohepcidin levels correlate with hepatic iron stores in chronic hepatitis
      C patients.
AB  - BACKGROUND/AIMS: Increased serum iron indices and hepatic iron stores are
      frequent in patients with chronic hepatitis C (CHC). The antimicrobial peptide
      hepdicin produced in the liver plays a pivotal role in iron homeostasis.
      METHODOLOGY: To determine the expression of hepcidin, the serum levels of
      prohepcidin were measured in 58 CHC patients and 144 healthy controls. The
      hepatic iron stores were scored by Perls' stain on liver biopsy specimens in 39
      CHC patients. The serum prohepcidin levels were correlated with biochemical
      inflammation markers, histological necroinflammation grades, hemoglobin levels
      and iron status in CHC patients. RESULTS: The concentrations of serum prohepcidin
      were significantly higher in CHC patients than in healthy controls (142.07 +/-
      67.06 vs. 89.07 +/- 37.32 ng/mL, p < 0.001). The CHC patients with positive
      hepatic iron stains had significantly higher serum prohepcidin levels than the
      CHC patients without (221.20 +/- 117.74 vs. 123.81 +/- 60.53 ng/mL, p = 0.037).
      The serum prohepdicin levels were not significantly correlated with the ages (r =
      -0.041, p = 0.760), hemoglobin (r = 0.127, p = 0.346), alanine aminotransferase
      (r = -0.032, p = 0.813), transferrin saturation (r = 0.025, p = 0.862), ferritin
      levels (r = 0.211, p = 0.133) and hepatic inflammation grades (r = 0.153, p =
      0.352) in CHC patients. CONCLUSIONS: The expression of serum prohepcidin is
      independent of the degree of hepatic inflammation as measured by the histological
      activity or aminotransferase level. The serum prohepcidin levels are associated
      with hepatic iron stains and significantly higher in CHC patients than in healthy
      controls. Our results suggest that CHC may induce the expression of hepcidin
      possibly by increased hepatic iron stores.

PMID- 19760960
TI  - Can hepatocellular cancer screening increase the proportion of long-term
      survivors?
AB  - BACKGROUND/AIMS: Historically, only 10% of hepatocellular cancer (HCC) patients
      are diagnosed with early stage, potentially curable disease. We prospectively
      screened chronic hepatitis virus-infected patients to determine 1) the proportion
      diagnosed with potentially curable HCC, and 2) survival following curative
      therapy. METHODOLOGY: The study included 5670 chronic hepatitis B (1,077, 19.0%),
      C (4,196, 74.0%), or both (397, 7.0%)-infected patients enrolled in a prospective
      screening program. Screening was every 6 months with serum alpha-fetoprotein
      (AFP) measurement and ultrasonography. Curative treatments included liver
      transplantation, resection, RFA, and/or ethanol injection. RESULTS: HCC was
      diagnosed in 464 (8.2%) patients. Of 1006 cirrhotic patients, 462 (45.9%)
      developed HCC. Curative treatment was possible in 319 (68.7%). The 2- and 5-year
      overall survival rates in the curative treatment group were 65% and 28%,
      respectively, compared to 10% and 0% in the advanced disease group (p < 0.001).
      CONCLUSION: Prospective screening of patients at high risk to develop HCC
      increases the proportion diagnosed with potentially curable disease. This may
      result in an increase of the number of long-term survivors. A screening strategy
      should focus on those patients with chronic hepatitis B or C virus infection that
      has progressed to cirrhosis since more than 40% of these patients will develop
      HCC.

PMID- 19760961
TI  - Liver metastases from uveal melanoma: clinical experience of hepatic arterial
      infusion of cisplatin, vinblastine and dacarbazine.
AB  - BACKGROUND/AIMS: Liver is the most common site of metastases in uveal melanoma.
      Hepatic arterial infusion of cytotoxic agents may be an effective method of
      controlling the disease in these patients. METHODOLOGY: A retrospective analysis
      of 10 patients with hepatic metastases of uveal melanoma treated with hepatic
      arterial infusion (HAI) of the combination of cisplatin, vinblastine and
      dacarbazine was performed. RESULTS: Two patients had an objective response, 4
      patients had stable disease and 4 patients had progressive disease. The median
      survival from the start of therapy was 16 (range 5 - 69) months. HAI of second
      line agents was of limited effectiveness. All patients with progressive disease
      died within one year while all patients with clinical benefit response (objective
      response or stable disease) survived more than one year. CONCLUSIONS: Present
      data demonstrate, in agreement with the literature, the effectiveness of HAI in
      the treatment of uveal melanoma metastatic to the liver. The HAI of combination
      of cisplatin, vinblastine and dacarbazine seems to have similar efficacy as other
      HAI regimens.

PMID- 19760962
TI  - A novel method for preparing microbubbles targeting hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: To develop an optimized formula for more stable and effective
      coupling of albumin microbubbles (MBs) to monoclonal antibodies (mAbs) using a
      biotin-avidin system. METHODOLOGY: Biotin modified albumin MBs were first linked
      with avidin (Av) followed by treatment with biotinylated mAbs. Each step was
      monitored using flow cytometry, and the results were summarized with an optimized
      formula. A hepatocellular carcinoma (HCC) and a normal human hepatocyte cell line
      were used to examine the effectiveness of this novel linkage strategy. RESULTS:
      The present experiments resulted in 96.05% of MBs bound to their microbubble
      shells. Av-Bio-MBs were conjugated to mAbs specific for the Hab18G/CD147 cell
      line. In vitro, CD147-specific MBs were found to bind to HCC cells, but not
      normal human hepatocyte cells. After exposure to Hab18G rosette-blocking mAb
      solution, few targeted MBs bound to HCC cells. CONCLUSIONS: Conjugation of MBs
      with biotinylated mAbs forming an Av-Bio-MB system is a novel and attractive tool
      for HCC-targeting and molecular imaging.

PMID- 19760963
TI  - Surgical radiofrequency ablation for treatment of hepatocellular carcinoma: an
      endoscopic or open approach.
AB  - Radiofrequency ablation (RFA) is widely used for the treatment of unresectable
      hepatocellular carcinoma (HCC) with cirrhosis, however, unexpected injuries to
      the adjacent organs remains the most critical problem after endoscopic
      radiofrequency ablation (RFA) using a percutaneous approach. The endoscopic RFA
      is a minimally invasive treatment for HCC with difficultly in the location due to
      limited percutaneous access. In this study, it was used an endoscopic approach or
      an open surgical approach for the treatment of 46 patients with unresectable HCC.
      There was difficulty in ablating the lesions due to limited percutaneous access.
      The endoscopic approach was assessed for 26 patients with primary HCC, and the
      open approach was used for 18 patients of recurrent HCC after surgical resection
      as well as the other 2 patients with multiple HCCs. The endoscopic RFA was
      performed using a laparoscopic approach for 20 cases and a thoracoscopic approach
      for 6 cases. The endoscopic RFA had significantly less intraoperative blood loss
      compared to the open RFA (56 g vs. 277 g; p < 0.001) as well as a reduced
      postoperative hospital stay (13 days vs. 16 days; p < 0.05). The occurrence of
      postoperative complications did not different between the two groups; 5 of 26
      cases of the endoscopic RFA, and in 3 of 20 cases of the open RFA. The local
      recurrence of HCC occurred in only 1 case for each group, and the patient
      survival did not differ significantly between the groups. Endoscopic RFA is a
      feasible and reliable therapy for unresectable primary HCCs in the patients with
      cirrhosis.

PMID- 19760964
TI  - ABO-incompatible adult liver transplantation when the anti-ABO antibody titer is
      high.
AB  - In comparison with ABO-compatible cases, ABO-incompatible liver transplantation
      has an increased risk of humoral rejection. The risk factors are the recipient's
      age (> or = 16 years) and elevated titers of anti-donor blood group antibodies.
      We report a case of adult A-to-O liver transplantation in which the recipient's
      preoperative IgG titer was 1:8192. Plasmapheresis, splenectomy, rituximab
      administration, and liver-directed anticoagulation therapy in addition to
      conventional immunosuppression effectively suppressed the antibody titer, thereby
      preventing humoral rejection. Preoperative administration of rituximab alone had
      minimal impact on antibody production, and a substantial amount of plasma cells
      remained in the spleen. This result is encouraging for high-risk ABO-incompatible
      liver transplantation and we recommend splenectomy combined with rituximab
      administration for such cases. Additionally, postoperative modulation of the
      recipient's immunity to the ABO-incompatible graft was noted, which is necessary
      for long-term survival of an ABO-mismatched allograft.

PMID- 19760965
TI  - Prognostic value of thymidine phosphorylase expression for pancreatic cancer.
AB  - BACKGROUND/AIMS: Thymidine phosphorylase (TP) has an angiogenic activity, but the
      prognostic value of TP has not been fully validated for pancreatic cancer. The
      aim of this study was to evaluate TP expression according to clinicopathological
      parameters to define its prognostic value for pancreatic cancer. METHODOLOGY:
      Forty-three patients with pancreatic ductal adenocarcinoma were examined
      retrospectively. TP expression and intratumoral microvessel density (IMD) were
      evaluated by immunohistochemistry. TP expression was analyzed according to
      clinicopathological parameters. RESULTS: Twenty-eight (65%) of 42 cases showed
      diffuse cytoplasmic and nucleic TP staining. IMD was significantly higher in TP
      positive tumors than in TP-negative tumors (27.7 +/- 8.9 vs. 18.1 +/- 4.4, p <
      0.01). TP levels were significantly higher in T3 and T4 tumors than in T1 and T2
      tumors (56% vs. 9.3%, respectively, p < 0.05). Patients with TP-positive tumors
      more frequently developed hepatic recurrence than those with TP-negative tumors
      after resection (p < 0.01). Patients with TP-positive tumors had a shorter
      survival than patients with TP-negative tumors (p < 0.05). CONCLUSION: TP
      expression can be used as a predictor of hepatic recurrence and as an unfavorable
      prognostic factor for pancreatic cancer.

PMID- 19760966
TI  - Prognostic factor of recurrence for resected digestive endocrine tumors.
AB  - BACKGROUND/AIMS: The aim of the present study was to identify the factors of
      recurrence for digestive endocrine tumours resected with curative intent.
      METHODOLOGY: 170 endocrine digestive tumours were reviewed from January 1997 to
      January 1997, Twenty eight patients were selected in this study. Localization of
      tumours were as follows: 14 duodenopancreatic (DP) and 14 Digestive (DT: 9 small
      bowel and 4 appendix). The following factors were investigated: primary site,
      hormonal clinical symptom, and differentiation. RESULTS: Twenty eight patients
      (12 men) were selected. Median age was 48 (range, 23-79) yrs. All resection of
      metastasis were performed during the same procedure of primary tumour resection.
      There were 14 DT and 14 non functional DP tumours. For 28 patients, the only
      factor of recurrence was endocrine pancreatic tumour (p = 0.02). For non
      functional DP, the rate of recurrence was significantly dependent on histology
      and the expression of ki67 antigen and presence of metastasis. Survival free of
      disease for DT were: 100%,80% at 1, 5 yrs, and for DP they were 93%, 50%, 33% at
      1, 3, 5 yrs, respectively. CONCLUSION: The expression of the Ki67 antigen and
      differentiation seem to be good indicators for DP recurrence and may need an
      adjuvant treatment despite the R0 resection.

PMID- 19760967
TI  - Biliary lesions associated with autoimmune pancreatitis.
AB  - BACKGROUND/AIMS: Characteristic radiological features of biliary lesions in
      patients with autoimmune pancreatitis (AIP) have not yet been identified.
      METHODOLOGY: Bile duct lesions and their relationships to other clinical findings
      were assessed in 43 AIP patients. RESULTS: Of the 43 AIP patients, 34 (79%) had
      bile duct stenosis. In all the 34 patients, the lower bile duct was involved; in
      21 of these, only the lower bile duct was involved, and in 13 patients, there was
      widespread wall thickening of the middle and upper bile duct where stenosis was
      not obvious on cholangiography. Furthermore, 4 patients with extensive bile duct
      involvement also had stenosis of the intrahepatic bile duct. All patients with
      bile duct involvement had involvement of the head portion of the main pancreatic
      duct. None of the 6 patients with involvement of only the body and/or tail
      portion of the main pancreatic duct had bile duct involvement. Gallbladder wall
      thickening was more frequently noted in patients with extensive bile duct
      involvement (p < 0.01). Serum IgG4 levels were significantly more elevated in
      patients with extensive bile duct involvement (p < 0.05). CONCLUSIONS: AIP
      patients with extensive bile duct involvement characterized by widespread wall
      thickening of the bile duct may have more active disease.

PMID- 19760968
TI  - Ampullary cancer and preoperative jaundice: possible indication of the minimal
      surgery.
AB  - BACKGROUND/AIMS: Obstructive jaundice is common symptom of carcinoma of the
      ampulla of Vater. In the present study we evaluated association between
      preoperative jaundice and prognosis and possible indication of the minimal
      surgery. METHODOLOGY: Clinicopathological features of 50 patients who underwent
      curative resection were examined retrospectively and statistically analyzed.
      RESULTS: Thirty-two of the 50 patients (64%) had preoperative jaundice, and these
      patients had poorer survival compared with these without jaundice (5 year
      survival 57.2% vs. 100%, p < 0.01). Preoperative jaundice, serum carbohydrate
      antigen 19-9 level, pancreatic invasion, lymphatic invasion, venous invasion,
      perineural invasion, duodenal invasion, margin status, lymph node metastasis, and
      T stage were shown to be significant prognostic factors. In the 18 patients
      without preoperative jaundice, lymphatic invasion was significantly related to
      lymph node metastasis. In addition, 12 of the 14 patients without jaundice and
      lymphatic invasion were diagnosed as T1N0 (stage IA) disease, and all the tumors
      were papillary or well-differentiated adenocarcinoma. CONCLUSIONS: Preoperative
      jaundice may reflect advanced-stage in case of ampullary cancer. Radical surgery
      may not be necessary in patients without preoperative jaundice if the tumor is
      diagnosed as a papillary or well-differentiated adenocarcinoma without lymphatic
      invasion.

PMID- 19760969
TI  - A new reconstructive procedure using intestinal pouch after
      pancreaticoduodenectomy with pancreaticogastrostomy.
AB  - The present study describes a new reconstructive technique that can be performed
      after pancreaticoduodenectomy, modified Child's with intestinal pouch, and with
      pancreaticogastrostomy. This new reconstructive procedure was developed, and
      termed it "Oida's intestinal pouch reconstruction after modified Child's
      procedure and pancreaticogastrostomy" with the aim of obtaining a sufficient
      volume of the remnant stomach after antrectomy with pancreaticoduodenectomy in
      order to prevent delayed gastric emptying in cases wherein pylorus-preserving
      pancreaticoduodenectomy is contraindicated. We consider the presented
      reconstructive technique to be one of the most favorable procedures for
      preventing delayed gastric emptying in patients who have undergone
      pancreaticoduodenectomy with pancreaticogastrostomy because pylorus-preserving
      pancreaticoduodenectomy (PPPD) was contraindicated.

PMID- 19760970
TI  - Celiac axis stenosis and lethal liver ischemia after pancreaticoduodenectomy.
AB  - Celiac axis stenosis can lead to a fatal hepatic ischemia after
      pancreaticoduodenectomy unless a simultaneous revascularisation of the celiac
      circulation is performed. In the present study are reported three cases of celiac
      axis stenosis, all of which had histologically confirmed periampullary cancer.
      Case 1: a 50-year-old male with a history of myocardial infarction and liver
      steatosis; visceral arteriography prior to the surgery demonstrated a celiac axis
      stenosis. Whipple operation was performed. After removing the specimen, no signs
      of liver ischemia were found (liver was cholestatic) and pulsation of the hepatic
      artery was strong. The patient died on the second postoperative day after an
      abrupt irreversible cardiac arrest. Autopsy proved acute severe hepatic ischemia.
      Case 2: a 64-year-old female. Preoperative visceral angiography showed
      significant celiac axis stenosis. As a first step of surgery the root of the
      celiac trunk was exposed, a fibrotic ring around it was divided. Standard D1
      pylorus preserving pancreaticoduodenectomy was performed. Case 3: a 58-year-old
      female without preoperative angiography, indicated for surgery. After an
      occlusion test of the gastroduodenal artery the liver became ischemic. Division
      of the fibrotic ring around celiac axis was performed together with a standard D1
      pylorus preserving pancreaticoduodenectomy. No postoperative complications were
      reported in both case 2 and 3.

PMID- 19760971
TI  - Spleen preserving laparoscopic distal pancreatectomy with segmental resection of
      splenic artery in a solid pseudo papillary tumor of the pancreas.
AB  - Laparoscopic distal pancreatectomy is suitable for benign and premalignant
      neoplasms located in the body and tail of the pancreas. In addition, spleen
      preservation following distal pancreatectomy for benign or low-grade malignant
      disease is known to be safe. We present a case of 32-year-old female patient with
      a solid pseudopapillary tumor of the pancreas treated by spleen-preserving
      laparoscopic distal pancreatectomy with segmental resection of the splenic artery
      and splenic vein intact. She had uneventful postoperative recovery and was
      discharged on the 6th postoperative day. Follow up Doppler-ultrasound scan showed
      no evidence of splenic infarction and well-preserved splenic blood flow.
      CONCLUSIONS: The surgical strategy of segmental resection of the splenic artery
      with intact splenic vein for spleen preservation seems feasible and represents an
      alternative option for spleen preservation in laparoscopic distal pancreatectomy.
      More clinical experience is required to address the advantages, limitations, and
      reproducibility of this technique.

PMID- 19760972
TI  - MDCT in the early recognition of isolated non-penetrating pancreatic transection.
AB  - Isolated pancreatic transection is rare. Associated main pancreatic duct injury
      is the principal determinant factor of outcome. Earlier computed tomographic
      scanner may be unreliable in determining the location and severity of pancreatic
      injury. Multiplanar reconstruction (MPR) and curved views of multidetector
      computed tomography are helpful in accurate diagnosis of pancreatic transection
      with the main pancreatic duct injury.

PMID- 19760974
TI  - A study on the association of histological types and TNM stages.
AB  - BACKGROUND/AIMS: To study the association between different histological types
      and staging of the gastric cancer. METHODOLOGY: Three hundred and fifty-one
      patients with gastric cancer and undergone D2 or greater gastrectomy were
      analyzed retrospectively. The association between TNM stages and histological
      types, including tubular adenocarcinoma (TUB), poorly differentiated
      adenocarcinoma (POR), signet-ring cell carcinoma (SIG), mucinous adenocarcinoma
      (MUC), and undifferentiated carcinoma (UND), were analyzed by univariate and
      multivariate analysis. RESULTS: Univariate analysis showed that the prevalence
      rates of T,M stages of POR, MUC, SIG, UND were not significantly different from
      that of TUB (all p values > 0.05). The prevalence rates of the N stage of POR,
      MUC, UND were significantly different from TUB p = 0.002, 0.011, 0.032). The
      prevalence rates of the N stage of SIG were not significantly different from TUB
      (p = 0.070). Multivariate analysis indicated that there was no histological type
      that was influencing factors on the T, M stages of gastric cancer. MUC, SIG, UND
      were not influencing factors on N stage, but, POR was influencing factor on the N
      stage (p = 0.011). CONCLUSIONS: There was no association between histological
      type and TNM stages, except the POR, which has a significant association with the
      N stage of gastric cancer.

PMID- 19760973
TI  - Expression of p53, p21 and p16 does not correlate with response to preoperative
      chemoradiation in gastric carcinoma.
AB  - BACKGROUND/AIMS: A retrospective evaluation was oerformed to determine whether
      the intensity of p53, p21 or p16 expression predicts response to preoperative
      chemoradiotherapy in locally advanced gastric carcinoma. METHODOLOGY: Thirty-six
      patients (cT2-4 or N+) were studied. Preoperative treatment consisted of 30-45Gy
      of radiation with continuous 5-fluorouracil and weekly cisplatin. Expression of
      p53, p21 and p16 in pretreatment biopsies was assessed by immunohistochemistry.
      Level of expression was determined from the intensity and extent of staining.
      Tumor downstaging was defined as a reduction of at least one T-stage level and/or
      finding of intense tumor regression in histopathologic examination. RESULTS:
      Seventeen patients responded to chemoradiation: 8 patients had pathologic
      complete response, 9 patients were downstaged. The multivariate analysis showed
      no significant influence of p53 (p = 0.76), p21 (p = 0.10) nor p16 (p = 0.70)
      expression upon tumor response. Response was found in 52% of patients with low,
      and in 40% of patients with high p53 staining (p = 0.21); in 54% of patients with
      low, and in 30% of patients with high p21 staining (p = 0.14); and in 48% of
      patients with low, and in 43% of patients with high p16 staining (p = 0.32).
      CONCLUSIONS: We found no significant influence of p53, p21 nor p16 expression
      upon response to preoperative chemoradiotherapy in gastric carcinoma.

PMID- 19760975
TI  - Prediction of successful weight reduction after laparoscopic adjustable gastric
      banding.
AB  - BACKGROUND/AIM: Compared with conventional pharmacological therapies, bariatric
      surgery has been shown to cause greater and- sustained weight loss. It was aimed
      to evaluate weight loss in obese patients after laparoscopic adjustable gastric
      banding surgery using information typically available during the initial
      evaluation studied before bariatric surgery and genes. METHODOLOGY: 74 patients
      undergoing laparoscopic adjustable gastric banding (LAGB) were enrolled.
      Artificial Neural Network technology was used to predict weight loss. RESULTS: We
      studied 74 patients consisting of 22 men and 52 women 2 years after operation.
      Mean age was 31.7 +/- 9.1 years. 27 (36.5%) patients had successful weight
      reduction (excess weight loss >50%) while 47 (63.5%) did not. ANN provided
      predicted factors on gender, insulin, albumin and two genes: re4684846_r,
      rs660339_r which were associated with success. CONCLUSION: Artificial neural
      network is a better modeling technique and the predictive accuracy is higher on
      the basis of multiple variables related to laboratory tests. Our finding gave
      demonstrated result that obese patients of successful weight reduction after
      laparoscopic adjustable gastric banding surgery were women, having little lower
      insulin and albumin, and carrying GG genotype on rs4684846 and with at least one
      T allele on rs660339. In these cases, weight loss will give better results.

PMID- 19760976
TI  - Mucin-producing gastric cancer: clinicopathological difference between signet
      ring cell carcinoma and mucinous carcinoma.
AB  - BACKGROUND/AIMS: Signet ring cell carcinoma and mucinous carcinoma are mucin
      producing gastric cancers. Their clinicopathological difference was obscure.
      METHODOLOGY: From December 1987 to July 2005, a total of 1612 gastric cancer
      patients received curative surgery, 128 patients with signet ring cell carcinoma
      and 48 with mucinous carcinoma were enrolled in this study. Clinicopathological
      data were compared between the two groups. RESULTS: Early stage (stage I and II)
      patients with mucinous carcinoma were associated with more male predominant (p =
      0.002), larger tumor size (p = 0.020), deeper cancer invasion (p < 0.001), and a
      worse 5-year overall survival (63.6% vs 88.2%, p = 0.012) than those with signet
      ring cell carcinoma. There was no significant difference between the two groups
      with advanced stage in 5-year overall survival. There is no significant
      difference in the initial recurrence pattern between the two groups. CONCLUSIONS:
      Patients with mucinous carcinoma had different biological behaviors with those
      with signet ring cell carcinoma, in particular early stage, hence had a worse
      survival.

PMID- 19760977
TI  - Association between cyclin D1 (CCND1) polymorphism and gastric cancer risk in
      Japanese population.
AB  - BACKGROUND/AIMS: A complex interaction of genetic and environmental factors is
      relevant in gastric carcinogenesis. Cyclin D1 (CCND1) is known to regulate
      function in G1 arrest and therefore, may play an important role in
      carcinogenesis. The present study aimed to clarify the effect of G870A
      polymorphism of the CCND1 gene on the risk of gastric cancer (GC) in a Japanese
      population. METHODOLOGY: Restriction fragment length polymorphism analysis was
      performed for polymorphisms at 870GA in the CCND1 gene in 392 GC and 359 cancer
      free subjects including 203 H. pylori positive gastritis and 156 H. pylori
      negative healthy stomach RESULTS: Non significant association was found between
      CCND1 G870A genotypes and risk of GC when compared to that of all non-cancer
      subjects (AA vs. GG+GA: OR = 1.13, 95% CI = 0.81-1.58, A carrier vs. GG: OR =
      1.13, 95% CI = 0.81-1.56), healthy stomach(AA vs. GG+GA: OR = 1.27, 95% CI = 0.81
      2.00, A carrier vs. GG: OR = 1.13, 95% CI = 0.8-1.84) and gastritis. (AA vs.
      GG+GA: OR = 1.03, 95% CI = 0.7-1.53, p = 0.92, A carrier vs. GG: 1.06, 95% CI =
      0.72-1.56, p = 0.77) No association was found between CCND1 genotypes and any of
      clinico-pathological features of GC. CONCLUSION: It appears that the G870
      polymorphism of CCND1 is not associated with the risk of GC in the Japanese
      population.

PMID- 19760978
TI  - Significance of VEGF and microvascular density in gastric carcinoma.
AB  - BACKGROUND/AIMS: The aim of this study is to observe the relationship between the
      expression of vascular endothelial growth factor (VEGF), microvascular density
      (MVD) and the pathological characteristics of gastric carcinoma. METHODOLOGY: A
      total of 87 cases of gastric carcinomas were examined by immunohistochemical
      staining, using anti-VEGF and anti-CD34 antibodies. RESULTS: VEGF positive
      staining was obtained in 62 out of 87 cases (71.2%). The MVD was 64.00 +/- 15.51
      (mean +/- SE) in VEGF-positive group and 48.33 +/- 12.71 in VEGF-negative group.
      CONCLUSIONS: The expression of VEGF is correlated with tumor angiogenesis, and
      VEGF plays an important role in new blood vessels formation. The expression of
      VEGF and MVD wereclosely correlated with the degree of differentiation and
      lymphatic metastasis, but not related to depth of cancer invasion, size of tumor,
      age or sex.

PMID- 19760979
TI  - Correlation between serum triglycerides and gastro-duodenal ulcer associated with
      low-dose aspirin.
AB  - BACKGROUND/AIMS: Aspirin significantly increases the risk of peptic ulcer. Since
      it remains to be determined whether gastroprotective agents should be used
      routinely in patients without risk factors who are taking aspirin, more risk
      factors for aspirin-related peptic ulcer should be detected. In the present study
      was investigated the effects of aspirin on upper gastrointestinal ulcer and
      potent risk factor for peptic ulcer associated with aspirin in a case-control
      study. METHODOLOGY: It was identified 137 newly diagnosed gastroduodenal ulcer
      cases from endoscopic examinees in the Gunma Prefectural Cardiovascular Center.
      Two controls per case were selected according to sex and age, and we determined
      274 controls. It was calculated OR and 95% CI of peptic ulcer for serum
      triglycerides. RESULTS: The use of low-dose aspirin without gastroprotective
      agents was found to be associated with the risk of peptic ulcer. High serum
      triglycerides were associated only with aspirin-related peptic ulcer. In
      contrast, no elevated OR of peptic ulcer was shown in cases without aspirin.
      CONCLUSIONS: The present study results suggest that hypertriglycerides might be
      one of the risk factors for peptic ulcer caused by aspirin. These findings
      indicate that gastroprotective therapy should be considered for preventing peptic
      ulcer associated with low-dose aspirin in patients with hypertriglyceridemia.

PMID- 19760981
TI  - Laparoscopic completion total gastrectomy in remnant gastric cancer: technical
      detail and experience of two cases.
AB  - The treatment of choice for remnant gastric cancer is resection by open
      conventional method, but due to adhesion and deformed anatomic structure,
      reoperation is one of the most complicated surgeries. We therefore introduce 2
      cases of laparoscopy-assisted completion total gastrectomy. One was 67 yrs old
      male who had radical subtotal gastrectomy with gastrojejunostomy due to stomach
      cancer 30 years ago. Gastric polyp was found in routine EGD. Biopsy results
      showed focal adenocarcinoma and laparoscopy-assisted total gastrectomy with Roux
      en-Y esophagojejunostomy was decided and performed. The other case was 65 yrs old
      male who went through radical subtotal gastrectomy with gastroduodenostomy 8
      years ago due to stomach cancer. Recur was diagnosed by routine EGD, and
      laparoscopic assisted total gastrectomy with Roux-en-Y esophagojejunostomy was
      done. As can be seen in this study, laparoscopy-assisted gastrectomy could be
      safely applied in remnant gastric cancer.

PMID- 19760980
TI  - 779 TC of CCK-1 intron 1 is associated with postprandial syndrome (PDS) in
      Japanese male subjects.
AB  - BACKGROUND/AIMS: The role of genetics in the susceptibility to functional
      dyspepsia (FD) is not well established. Cholecystokinin (CCK) is released from
      enteroendocrine cells in the duodenal mucosa after food ingestion and signals
      satiation through peripheral or central actions. A common polymorphisms of CCK
      and it's receptor gene has been shown to be associated with panic disorder and
      schizophrenia. It was investigated the prevalence of CCK polymorphism in
      dyspeptic patients in a Japanese population. METHODOLOGY: A total of 124
      dyspeptic patients, 119 non-symptomatic healthy controls participated in this
      study. Dyspeptic patients were also classified by Rome III criteria. T779C of
      Cholecystokinin (CCK)-1 intron 1, by polymerase chain reaction-restriction
      fragment length polymorphism. H. pylori infection status was examined by
      histology or antibody against H. pylori. RESULTS: Although frequency of CCK-1
      polymorphisms in overall dyspeptic patients, subgroups by Roma III criteria and
      non-symptomatic healthy controls did not show any significant differences, 779 T
      carriers significantly increased the risk of postprandial syndrome (PDS) in male
      subjects (53.5% vs, 84.2; OR = 4.63, 95% CI = 1.24-17.31, p = 0.018). This
      significant association was also remained after logistic regression analysis with
      adjustment for age and H. pylori infection status (OR = 4.99, 95% CI = 1.31
      18.95, p = 0.018). In female and different H. pylori infection status, no
      significant association was observed between CCK-1 polymorphisms and dyspepsia.
      CONCLUSION: Our data suggest that the 779 T carriers of CCK-1 intron 1 is
      associated with an increased risk of PDS in Japanese male subjects.

PMID- 19760982
TI  - Growth hormone treatment: evidence, practice, and emerging issues.

PMID- 19760983
TI  - Clinical management of growth hormone therapy for children.

PMID- 19760984
TI  - Clinical management of growth hormone therapy in adults.
AB  - GH replacement is an effective and rational therapy for adult men and women with
      known pituitary disease or risk factors for hypopituitarism; for example, severe
      head trauma or pituitary irradiation, provided that GHD is proven. Only at-risk
      adults should be tested, and adults with childhood GHD should be retested before
      prescribing GH for adult needs. A neuroendocrine review should be considered in
      all cases of TBI and SAH. The AACE, Endocrine Society, and GRS have issued
      detailed GHD treatment guidelines. Diagnostic evaluations should follow these
      guidelines, and physicians should stay abreast of changing information about
      testing cut-points and the use of IGF-1 as a marker for GHD. The pros and cons of
      GH treatment must be discussed with each patient, after which GH doses should be
      individualized and titrated to maximum efficacy with minimal side effects. Off
      label use of GH therapy as an anti-aging treatment or sports enhancement is
      clearly at odds with current guidelines and should not be prescribed under any
      circumstances. GH replacement therapy has been shown to improve the clinical
      features of GHD in adults, although there yet have been no studies on endpoints
      such as cardiovascular events, fractures, and death. When used in an approved and
      ethical fashion for the defined population, this treatment can enhance the health
      and well-being of the many patients who suffer from the complications of GHD.

PMID- 19760985
TI  - Plan and pharmacy perspectives: growth hormone therapy, formulary, and benefit
      authorization.
AB  - Overall, third-party payers accept many of the indications for GH therapy. The
      evidence of pathology in GHD and other causes of short stature are compelling,
      and the support for improvement in height and metabolic outcomes with GH therapy
      in most of these disorders is well accepted. To provide well-intentioned coverage
      and safe and effective treatments to clients who most need it, health plans must
      do due diligence and ensure that the indications for which they cover rhGH are
      compelling, beneficial, and safe. Ensuring that those patients who will most
      benefit from GH therapy do receive treatment may require that unsupported
      diagnoses are excluded from coverage.

PMID- 19760986
TI  - Genome wide association studies: way forward or work backwards?

PMID- 19760987
TI  - Hematological problems and liver disease.
AB  - There has been significant progress in the understanding of the pathophysiologic
      basis of common haematological problems like cytopenias, coagulopathies and
      thrombophilic disorders in the background of liver disease. Diagnosis has
      improved with newer tests like detection of JAK2 mutation and better radiological
      imaging. Additionally, therapeutic options have expanded with availability of
      drugs like activated factor VII and eltrombopeg and improved expertise in
      procedures like TIPSS for treatment of the Budd-Chiari syndrome. Thus, there is
      increasing need for coordinated management of these problems by the hematologist
      and gastroenterologist. This article overviews the interface between hepatology
      and hematology and elaborates on some of the common problems encountered.

PMID- 19760988
TI  - Pancreatic diabetes.
AB  - Pancreatic endocrine insufficiency secondary to destruction of acinar cells is a
      well known complication of chronic pancreatitis (CP). Of all patients with
      diabetes mellitus, 0.5-1% is secondary to CP. The frequency of occurrence of
      diabetes in CP is about 40-60%. This figure varies according to the aetiology,
      extent of calcification, and duration of the disease. Pancreatic diabetes is more
      commonly associated with alcoholic and tropical calcific pancreatitis of long
      duration. The pathophysiology of pancreatic diabetes is related to beta cell
      failure and reduced insulin secretory capacity. The development of pancreatic
      diabetes calls for careful evaluation and management to prevent long term
      complications. Pancreatic cancer is a known complication of chronic pancreatitis
      and sometimes manifests with new onset diabetes. As destruction of pancreatic
      tissue in CP leads to depletion of both insulin and glucagon-producing cells of
      the islets of Langherhans, pancreatic diabetics are usually not prone to
      ketoacidosis. A trial of oral hypoglycemic agents followed by insulin therapy
      when the need arises has been the line of management thus far in these patients.
      This review focuses on the prevalence, unique pathophysiological aspects,
      clinical features and special issues in the management of diabetes secondary to
      chronic pancreatitis.

PMID- 19760989
TI  - Probiotic-induced changes in the intestinal epithelium: implications in
      gastrointestinal disease.
AB  - There is resurgent interest in the use of probiotics to maintain gastrointestinal
      and systemic health, driven by recent advances in knowledge of bacterial
      interactions with the epithelium and innate immune system of the intestine. The
      effects of probiotic bacteria on the intestinal epithelium and their downstream
      consequences are reviewed. Probiotics prevent pathogen adherence and invasion of
      the epithelium, partly by blocking adherence sites but also by upregulating gene
      expression of MUC2 and of antimicrobial peptides. Metabolic effects of probiotics
      on the intestinal epithelium include production of short chain fatty acids which
      influence epithelial cell metabolism, turnover and apoptosis. Bacterial
      metabolism of unabsorbed dietary constituents with production of free radicals
      and phenolic metabolites can lead to DNA damage and cancer; probiotics restore
      eubiosis and potentially prevent this. Probiotics alter expression and
      redistribution of tight junction proteins and reduce intestinal permeability
      limiting absorption of noxious molecules from the gut lumen. Most studied are the
      effects of probiotics on epithelial cells which are the first line of innate
      immune-capable cells that encounter luminal flora. Probiotics, through secreted
      molecules, influence the innate inflammatory response of epithelial cells to
      stimuli from the gut lumen, and reduce mucosal inflammation. Through effects on
      dendritic, and possibly epithelial, cells they influence naive T cells in the
      lamina propria of the gut and thus influence adaptive immunity. These varied
      effects of probiotics have implications for the treatment of several
      gastrointestinal diseases including antibiotic-associated colitis, acute
      gastroenteritis, inflammatory bowel disease, colon cancer, and irritable bowel
      syndrome.

PMID- 19760990
TI  - Lactose hydrogen breath test versus lactose tolerance test in the tropics: does
      positive lactose tolerance test reflect more severe lactose malabsorption?
AB  - BACKGROUND: We compared the lactose hydrogen breath (lactose HBT) and lactose
      tolerance tests (LTT) in their ability to diagnose lactose malabsorption (LM).
      METHODS: Fasting and post-lactose (50 g) breath hydrogen and blood sugar were
      tested in patients with irritable bowel syndrome (IBS). Persistent rise in breath
      hydrogen by 20 ppm and failure of blood sugar to rise by >20 mg/dL above basal
      level, were considered positive lactose HBT and LTT, respectively. Symptoms of
      diarrhoea, bloating, abdominal pain and flatulence were noted. RESULTS: Of 203
      patients, 11 demonstrated high basal breath hydrogen and hence, 192 (age 37+/-14
      years, 134 male) were included in the study. 125 (65%) and 137 (71%) were lactose
      HBT and LTT positive, respectively. 102/125 lactose HBT positive patients were
      LTT positive and 35/67 lactose HBT negative patients were LTT positive. 62/192
      (32%) developed symptoms following lactose ingestion, which tended to be more in
      the LTT positive (49/137, 36% vs. 13/55, 24% p=0.07) but not in the lactose HBT
      positive patients (44/125, 35% vs. 18/67, 27% p=0.2). Peak breath hydrogen was
      higher (38+/-37 vs. 66+/-43; p<0.01) in LTT positive than negative patients. Peak
      level of breath hydrogen inversely correlated (58+/-43 vs. 10+/-23; p<0.001) with
      change in blood glucose following lactose ingestion. CONCLUSIONS: Positive LTT is
      associated with a higher breath hydrogen score than negative LTT. There was a
      trend towards more frequent symptom development following lactose load in LTT
      positive but not in lactose HBT positive patients. LTT is an easy and efficient
      test for diagnosis of LM.

PMID- 19760991
TI  - Assessment of vagotomy status with postprandial urinary alkaline tide.
AB  - AIM: This study was carried out to assess whether the postprandial urinary
      alkaline tide, as a marker for the completeness of vagotomy, is dependent on the
      nature of the test meal, whether it is affected by proton pump inhibitor therapy,
      and whether it is reliable. METHODS: The postprandial urinary alkaline tide
      (PUAT) pattern was prospectively assessed in three different study groups and one
      control group of healthy volunteers. The three study groups were as follows; A (n
      = 20) i.e. the Proton Pump Inhibitor (PPI) Group; B (n = 25) i.e. the Truncal
      Vagotomy (TV) Group; and C (n = 5) i.e. the Recurrent Ulcer (RU) Group. Urinary
      pH was measured by a pocket digital pH meter. RESULTS: Postprandial urinary
      alkaline tide in the control group was significantly higher compared to the
      fasting levels. Liquid diet did not elicit a significant urinary alkaline tide
      response. There was a statistically significant fall in both fasting urinary pH
      (5.34 +/- 0.70 vs. 4.80 +/- 0.61, p = 0.031) and the postprandial alkaline tide
      (6.99 +/- 0.79 vs. 4.94 +/- 0.63, p = 0.0001) after taking proton pump
      inhibitors. In the truncal vagotomy and gastrojejunostomy group it was found that
      there was a significant fall in both the mean fasting (5.28 +/- 0.58, vs. 4.92 +/
      0.66, p = 0.032) and the postprandial urinary pH (6.29 +/- 0.92 vs. 5.09 +/-
      0.73, p = 0.0001) following surgery. CONCLUSION: This study establishes that
      simple measurement of the urinary pH before and after a standard test meal can be
      used as an accurate routine test for the completion of vagotomy. It also showed
      that proton pump inhibitors abolish the alkaline tide and therefore must be
      discontinued before measuring the alkaline tide. Liquid test meal was not
      effective in eliciting an alkaline tide as compared to a solid meal.

PMID- 19760992
TI  - Laparoscopic management of common bile duct "Stentolith".

PMID- 19760993
TI  - A case of misdiagnosis: solitary rectal ulcer as Crohn's colitis.

PMID- 19760994
TI  - Unexpected detection of an occult cecal pole tumour due to technical delay in
      commencing computerised tomographic scan of the upper abdomen.

PMID- 19760995
TI  - Giant fibrovascular polyp of the esophagus: a case report.

PMID- 19760996
TI  - Postoperative intestinal perforation with multiple suture granulomas.

PMID- 19760997
TI  - A case of eventrated liver mass presenting as a late outcome of hepatopulmonary
      amoebiasis.

PMID- 19760998
TI  - Gastric atrophy and Helicobacter pylori infection in children.
AB  - AIM: To assess the prevalence of gastric atrophy (GA) in Tunisia (a high
      prevalence region for Helicobacter pylori), and describe its histological,
      clinical and endoscopic features in children. METHODS: 345 children, 151 male and
      194 female, mean age 8.6 +/- 3.7 years, underwent upper gastrointestinal (UGI)
      endoscopy with gastric biopsies for recurrent abdominal pain (n=232, 67.2%),
      vomiting (n=72, 20%) associated with or without upper gastrointestinal bleeding
      (n=59, 17.1%) and miscellaneous causes (n=53, 15.4 %). Biopsies performed both in
      the gastric antrum (n=2) and corpus (n=2) were analysed for histological
      assessment according to the updated Sydney classification system and bacterial
      culture. A positive result was recorded where histology and/or culture were
      positive, confirming the presence of H. pylori infection (H. pylori +ve). A
      negative result was recorded when both tests were concomitantly negative (H.
      pylori -ve). RESULTS: 9.3% (32/345) of the total population, and 14.5% (32/221)
      of chronic gastritis patients exhibited GA, M/F: 16/16, mean age (SD) 9.4 (3.4)
      years. Amongst the 32 children with GA, 30 (93.7%) were H. pylori +ve and 2
      (6.3%) were H. pylori -ve. GA was localised in the antrum (n=26, 81.2%), the
      fundus (n=2, 6.3%) and was also seen in both (n=4, 12.5%). GA was categorised as
      mild, grade 1 (n=18, 56.3%); moderate, grade 2 (n=13, 46.6%); and severe, grade 3
      (n=1, 3.1%). GA was associated with mild active gastritis in 18 cases (56.3%).
      The prevalence of moderate or severe antral GA was detected in 9/26 (34.6%) of H.
      pylori +ve vs. any of H. pylori -ve (p=0.4), whereas GA in the corpus was
      detected in 1/2 (50%) vs. none, respectively. None exhibited intestinal
      metaplasia. There were no clinical features specific to this pathology. UGI
      endoscopy in GA patients showed nodular gastritis (n=17, 53.1%), congestive
      gastritis (n=9, 28.1%), and normal tissue (n=6, 18.8%). GA was significantly
      associated with H. pylori infection (p<0.0001) and nodular gastritis (p<0.005).
      CONCLUSION: GA was found in 9.3% of Tunisian children undergoing UGI endoscopy
      and was significantly associated with H. pylori infection and nodular gastritis.

PMID- 19760999
TI  - The development of intrapulmonary arteriovenous shunts as a poor prognostic
      factor following surgery for biliary atresia.
AB  - BACKGROUND & AIMS: Chronic liver disease requiring liver transplantation is a
      common occurrence following corrective surgery for extrahepatic biliary atresia
      (EHBA). The formation of intrapulmonary arteriovenous shunts (IPS) is a well
      known feature of chronic liver disease. The aim of this study was to investigate
      the development of IPS and its prognostic significance in postoperative patients
      with EHBA. METHODS: Fourteen patients who underwent Kasai's portoenterostomy
      during 1993-2005 were included in the study. The clinical features, hepatobiliary
      scintigraphy and biochemical liver function tests were recorded. A transthoracic
      contrast enhanced echocardiogram using a four-chamber view was performed in all
      patients within a week of the Kasai's procedure by injecting 5 mL of hand
      agitated saline solution into a peripheral vein. The opacification of
      microbubbles in the left atrium 3-6 minutes after their emergence in the right
      atrium was considered diagnostic of IPS. The contrast enhanced echocardiogram was
      repeated 6 months after the Kasai's procedure in all patients. RESULTS: Nine
      patients were clinically asymptomatic after surgery. HIDA scan was excretory in
      all 14 patients at the time of the study, although 5 patients were jaundiced. The
      serum bilirubin increased in 2 patients after surgery; both these patients were
      jaundiced and developed ascites and 1 expired one year after surgery. Contrast
      enhanced echocardiogram was negative for IPS in all 14 initially. In the follow
      up evaluation the only patient who died was the one who had developed IPS.
      CONCLUSIONS: There is a risk of developing IPS following a failed Kasai's
      portoenterostomy in patients of EHBA. Contrast enhanced echocardiography can be
      used to serially monitor these patients for early detection of this complication.
      It can be used to predict prognosis after hepatic portoenterostomy and can be
      extremely useful in selecting patients who will need liver transplant on
      priority.

PMID- 19761000
TI  - Influence of timing on performance of laparoscopic cholecystectomy for acute
      biliary pancreatitis.
AB  - AIM: Gallstone disease is the most common cause of acute pancreatitis.
      Cholecystectomy is mandatory to avoid recurrence of pancreatitis. Our objective
      was to evaluate the results of laparoscopic cholecystectomy (LC) in patients with
      gall-stone induced pancreatitis. METHODS: All patients presenting to us within
      the time frame from February 2004 to June 2008 with acute biliary pancreatitis
      were included in the study. The severity of pancreatitis was assessed by Ranson's
      criteria. ERCP and endoscopic sphincterotomy was performed when the common bile
      duct (CBD) was dilated (>6 mm) with either calculi or sludge as seen on imaging.
      Patients with successful ERCP with predicted demanding laparoscopic
      cholecystectomy were discharged instead for an elective LC, 4-6 weeks later.
      Patients with mild pancreatitis (with Ranson's score of 3 or less) and predicted
      uncomplicated LC underwent surgery at the same admission. The difficulty of the
      procedure was determined by the presence of adhesions in the gallbladder area,
      dissection in Calot's triangle, tackling the dilated cystic duct, intra-operative
      bleeding, and the need for a drain. RESULTS: A total of 26 patients (12 male and
      14 female; age range 23-75 years) with acute biliary pancreatitis comprised the
      study group. Eleven patients with suspected choledocholithiasis underwent ERCP
      and clearance of the CBD was done in all of them. Nine patients (2 ERCP and 7 non
      ERCP) underwent early LC in the same admission. Seventeen patients (9 ERCP and 8
      non-ERCP) were predicted as difficult cases for LC and underwent delayed LC. No
      patient had recurrent pancreatitis in the interval period. CONCLUSION: There was
      no significant difference in the operative difficulty between early and delayed
      LC when patients were selected for timing of LC based on pre-defined criteria.

PMID- 19761001
TI  - Clinical research boom in India: opportunism or opportunity?

PMID- 19761002
TI  - The environmental health workforce NEHA's workforce development committee.

PMID- 19761003
TI  - PACE in Florida: fomenting leadership in hard times.

PMID- 19761004
TI  - Survey of the home sewage disposal systems in northeast Ohio.
AB  - This article reports on failure rates in onsite sewage treatment systems (STS)
      that were found as part of a comprehensive seven-county survey that was performed
      under the auspices of the Northeast Ohio Areawide Coordinating Agency (NOACA)
      during the summer of 2000. The goal was to determine the percentage of onsite,
      individual home wastewater systems that were "failing." A system was identified
      as "failing" if, upon inspection, it had observable surfacing of effluent from
      the treatment system. A certified soil scientist conducted each on-site
      investigation to ensure consistency in methodology and to provide verification of
      soil types for each installation. The survey revealed that between 12.7% and
      19.7% of the onsite wastewater treatment systems are allowing wastewater to
      surface as opposed to infiltrate (at the 95% confidence interval). The rate of
      failure does not vary significantly between aerobic and septic systems or between
      systems with or without filters.

PMID- 19761005
TI  - University students' hand hygiene practice during a gastrointestinal outbreak in
      residence: what they say they do and what they actually do.
AB  - Published research on outbreaks of gastrointestinal illness has focused primarily
      on the results of epidemiological and clinical data collected postoutbreak;
      little research has been done on actual preventative practices during an
      outbreak. In this study, the authors observed student compliance with hand
      hygiene recommendations at the height of a suspected norovirus outbreak in a
      university residence in Ontario, Canada. Data on observed practices was compared
      to postoutbreak self-report surveys administered to students to examine their
      beliefs and perceptions about hand hygiene. Observed compliance with prescribed
      hand hygiene recommendations occurred 17.4% of the time. Despite knowledge of
      hand hygiene protocols and low compliance, 83.0% of students indicated that they
      practiced correct hand hygiene during the outbreak. To proactively prepare for
      future outbreaks, a current and thorough crisis communications and management
      strategy, targeted at a university student audience and supplemented with proper
      hand washing tools, should be enacted by residence administration.

PMID- 19761006
TI  - Food safety education for Arabic speakers in the food service industry.

PMID- 19761007
TI  - Comment on "An observational study on the effectiveness of point-of-use
      chlorination".

PMID- 19761008
TI  - Information networks: a proposed linkage of state journals and bulletins.

PMID- 19761009
TI  - Improving environmental assessments during foodborne outbreaks.

PMID- 19761010
TI  - Bringing this year's AEC to everyone!

PMID- 19761011
TI  - Finding common ground between members.

PMID- 19761012
TI  - Creating a culture of safety: why CEOs hold the key to improved outcomes.
AB  - When the nonprofit VHA foundation, created by VHA Inc., Irving, Texas, embarked
      on a national patient safety initiative it looked first to outside industries,
      gathering information and ideas from pioneers in nuclear energy, aviation, the
      military and other innovation-rich fields known for safety excellence.

PMID- 19761013
TI  - Strategies for application of ubiquitous technology.
AB  - The study aims to address issues to be considered when applying ubiquitous
      technologies to hospital management. First, it is imperative to consider
      information policy at home and abroad and standardization trends. Secondly,
      hospitals need to come up with an integrated and flexible plan based on their
      strategies to adopt ubiquitous technologies. Thirdly, the effects of new IT
      technologies on the entire system and the creditability of hospital should be
      considered as well. Fourthly, the medical system and economic climate of the
      nation should be considered. The health-care industry is characterized by high
      labour costs, and IT technology is adopted to improve efficiency. Fifthly, the
      business aspects of hospital management should be considered. Lastly, the
      adoption of ubiquitous technologies cannot be the objective. It is important to
      pursue the most possible plan to realize the core objectives of strategic
      activities set by hospital.

PMID- 19761014
TI  - Creating work environments that are violence free.
AB  - Workplace violence is a global phenomenon with recent research demonstrating that
      the incidence of violence is high and increasing, particularly in health-care
      settings. The current study reported the prevalence of workplace violence in
      nursing and examined the impact of it on nurses' work life and health based on a
      national Canadian survey. Results demonstrated that workplace violence
      significantly increases the likelihood of nurses' absenteeism, job
      dissatisfaction and poor physical and mental health, and can negatively impact
      quality of nursing care. Various workplace violence interventions and the need
      for further research in addressing the issue of violence are discussed.

PMID- 19761015
TI  - High 5s: addressing excellence in patient safety.
AB  - The High 5s project is a multi-country, multi-agency collaborative initiative to
      improve patient safety around the world. Launched by the World Health
      Organization (WHO) in 2006, the mission of the Project is to facilitate
      implementation and evaluation of standardized patient safety solutions within a
      global learning community to achieve measurable, significant, and sustainable
      reductions in challenging patient safety problems in hospitals from several
      countries over five years. The High 5s project is best characterized as
      supporting the development and application of innovative, specific standard
      operating protocols (SOPs) through the collection, reporting and analysis of
      data, and establishing an electronic collaborative learning community.

PMID- 19761016
TI  - Decrease in acute coronary syndrome mortality in Pleven district: implementation
      of scientific evidence into everyday practice.
AB  - Cardiovascular mortality in Bulgaria has increased for the last 25 years,
      contrary to the rest of the EU countries. One of the reasons is high in-hospital
      mortality due to acute myocardial infarction. The Bulgarian Cardiac Institute has
      established a modern cardiac hospital with a catheterization laboratory (cathlab)
      in the Medical University in Pleven, which helps it decrease acute coronary
      syndrome (ACS) mortality, taking all the necessary steps according to the
      guidelines of the European Society of Cardiology (ESC).

PMID- 19761017
TI  - Constraints in nurses' use of HIV protective barriers in the care of PLWHA in the
      University College Hospital, Ibadan, Nigeria.
AB  - This survey examines the constraints limiting nurses' use of protective barriers
      in the care of people living with HIV/AIDS in Ibadan, Nigeria. 270 females and 5
      male nurses working in UCH were purposively selected. A self-developed
      questionnaire was used during data collection. Data was analyzed using
      descriptive statistics and chi square. Results about nurses' use of protective
      devices (eg gloves) showed that 206 (94.2%) use PB always, 15 (5.5%) frequently
      use PB and 1 (0.4%) occasionally use PB. Chi-square test shows significant
      differences between constraints in the use of PB in the care of PLWHA and
      adherence to HIV/AIDS universal precautions (chi2 = 15.22, 1df, P < 0.05). It was
      concluded that nurses in the selected setting were faced with constraints in the
      use of PB and as such were inadequately protected from blood-borne diseases
      especially when caring for PLWHA.

PMID- 19761018
TI  - Secure growth. Access control system expands with hospital.

PMID- 19761019
TI  - Doctors' orders. Physicians key to hospital design effort.

PMID- 19761020
TI  - Finish line. Making the best selections in flooring, walls, hard surfaces and
      upholstery.

PMID- 19761021
TI  - How clean is clean? New technologies, monitoring practices gain traction.

PMID- 19761022
TI  - Some illumination.A look at health facility lighting standards.

PMID- 19761024
TI  - Readers' perspectives. Remotely hosted ambulatory electronic health records.

PMID- 19761023
TI  - Respect for seniors. Environmental services and long-term care.

PMID- 19761025
TI  - Getting a grip on billing.

PMID- 19761026
TI  - Tiny hospital has big I.T. agenda.

PMID- 19761027
TI  - Building 21 st century data centers.

PMID- 19761028
TI  - Mass General 'aims' to improve.

PMID- 19761029
TI  - Small fish, big data pond.

PMID- 19761030
TI  - Doc: EHR benefits outweigh pain.

PMID- 19761032
TI  - Stimulus funds take aim at treatment protocols. Cutting costs at root of federal
      efforts to trim healthcare spending.

PMID- 19761031
TI  - Keeping tabs on tablets.

PMID- 19761033
TI  - Managing orthopedic implant costs takes imagination and a smart game plan. Many
      hospitals have succeeded in controlling implant costs.

PMID- 19761034
TI  - Hospitals catch a break on casting, splinting supply prices. Latest pricing poll
      runs nearly identical to 2005 rates.

PMID- 19761035
TI  - How one IDN gave cold shoulder to high energy costs. Hospital invests and warms
      to far-reaching power savings.

PMID- 19761036
TI  - Malaria vaccine: latest update and challenges ahead.
AB  - Development of an effective malaria vaccine remains one of the biggest challenges
      faced by modern science. Although in the last decade tremendous advances have
      taken place in the design, construction and testing of malaria vaccines, many
      questions still remained unanswered. This review highlights exclusively some of
      the exciting and most recent progress in the development and clinical testing of
      candidate malaria vaccines and points out some of the outstanding scientific
      issues and technological challenges that must be met to develop a successful
      vaccine.

PMID- 19761037
TI  - Endocrinal toxicity of industrial solvents--a mini review.
AB  - Endocrine system can be affected by various organic compounds. The review
      describes the effects of major industrial solvents on adrenal, thyroid and
      parathyroid glands in man and experimental animals. Further, their toxicity in
      pancreas, pituitary, testis and ovary has also been discussed. An attempt has
      been made to offer a historical and general information on solvent toxicity in
      endocrine glands. Possible mechanisms, in brief, have also been discussed.
      Endocrine toxicity caused by industrial solvents deserves more attention than
      hitherto paid. An understanding of hormonal disorders caused by industrial
      solvents will be important from occupational health point of view.

PMID- 19761038
TI  - Parthenogenesis and somatic cell nuclear transfer in sheep oocytes using
      Polscope.
AB  - Parthenogenesis and Somatic cell nuclear transfer (SCNT) techniques, offer a
      unique approach to manipulate the genetic composition of derived human embryonic
      stem cells - an essential step if the full opportunities for disease modeling,
      drug discovery or individualized stem cell therapy are to be realized. The
      present study describes the use of sheep oocytes to acquire expertise and
      establish methods to reconstruct embryos for obtaining blastocysts before
      venturing into human SCNT where the oocytes are a very precious starting
      material. Maturation of sheep eggs in vitro for 20-24 hr resulted in 65%
      metaphase II (MII) eggs which were either parthenogenetically activated using
      calcium ionomycin or ethanol or subjected to SCNT using cumulus cell as somatic
      cell. Sixteen blastocysts were produced by parthenogenetic activation of 350 eggs
      whereas reconstructed embryos, after SCNT carried out in 139 eggs, progressed
      only up to morula stage. The procedure of parthenogenesis and SCNT will be useful
      to generate autologous ES cells using human eggs.

PMID- 19761039
TI  - Effect of Hibiscus rosa sinensis on reserpine-induced neurobehavioral and
      biochemical alterations in rats.
AB  - Effect of methanolic extract of Hibiscus rosa sinensis (100-300 mg/kg) was
      studied on reserpine-induced orofacial dyskinesia and neurochemical alterations.
      The rats were treated with intraperitoneal reserpine (1 mg/kg, ip) for 3 days
      every other day. On day 5, vacuous chewing movements and tongue protrusions were
      counted for 5 min. Reserpine treated rats significantly developed vacuous chewing
      movements and tongue protrusions however, coadministration of Hibiscus rosa
      sinensis roots extract (100, 200 and 300 mg/kg, per orally) attenuated the
      effects. Biochemical analysis of brain revealed that the reserpine treatment
      significantly increased lipid peroxidation and decreased levels of superoxide
      dismutase (SOD), catalase (CAT) and glutathione reductase (GSH), an index of
      oxidative stress process. Coadministration of extract significantly reduced the
      lipid peroxidation and reversed the decrease in brain SOD, CAT and GSH levels.
      The results of the present study suggested that Hibiscus rosa sinensis had a
      protective role against reserpine-induced orofacial dyskinesia and oxidative
      stress.

PMID- 19761040
TI  - Antihyperglycemic, antihyperlipidemic and antioxidant effects of Dihar, a
      polyherbal ayurvedic formulation in streptozotocin induced diabetic rats.
AB  - Present investigation was undertaken to evaluate antihyperglycemic,
      antihyperlipidemic and antioxidant activities of Dihar, a polyherbal formulation
      containing drugs from eight different herbs viz., Syzygium cumini, Momordica
      charantia, Emblica officinalis, Gymnema sylvestre, Enicostemma littorale,
      Azadirachta indica, Tinospora cordifolia and Curcuma longa in streptozotocin
      (STZ, 45 mg/kg iv single dose) induced type 1 diabetic rats. STZ produced a
      significant increase in serum glucose, cholesterol, triglyceride, very low
      density lipoprotein, low density lipoprotein, creatinine, and urea levels in
      diabetic rat. Treatment with Dihar (100 mg/kg) for 6 weeks produced decrease in
      STZ induced serum glucose and lipids levels and increased insulin levels as
      compared to control. Dihar produced significant decrease in serum creatinine and
      urea levels in diabetic rats. There was a significant decrease in reduced
      glutathione, superoxide dismutase, catalase levels and increase in
      thiobarbituiric acid reactive species levels in the liver of STZ-induced diabetic
      rats. Administration of Dihar to diabetic rats significantly reduced the levels
      of lipid paroxidation and increased the activities of antioxidant enzymes. The
      results suggest Dihar to be beneficial for the treatment of type 1 diabetes.

PMID- 19761041
TI  - Antihyperglycemic and antioxidative potential of hydroalcoholic extract of Butea
      monosperma Lam flowers in alloxan-induced diabetic mice.
AB  - Daily treatment of alloxan-induced diabetic animals with 50% ethanolic extract of
      B. monosperma flowers (BMEE) for 45 days significantly lowered blood glucose
      level thereby preventing steep onset of hyperglycemia which was observed after
      alloxan administration and maintained body weight and blood glucose level close
      to the values observed in normal control and glibenclamide-treated diabetic mice.
      Moreover, the level of serum total cholesterol, triglyceride, low-density
      lipoprotein and very low-density lipoprotein cholesterol were also lowered,
      whereas the level of high-density lipoprotein cholesterol, which was reduced in
      untreated diabetic animals, was significantly elevated. Oxidative damage in the
      liver, pancreas and kidneys of diabetic mice as evidenced by a marked increment
      in the level of thiobarbituric acid reactive substances and also a distinct
      diminution in glutathione content was nullified by BMEE. Activities of
      antioxidant enzymes were also assessed in all the experimental groups. These
      enzymes registered a decline in their activity in diabetic animals thus revealing
      the damaging effects of free radicals generated due to alloxan exposure but their
      activities were reverted towards near normal range in BMEE-administered mice thus
      indicating the antioxidant efficacy of the drug in resisting oxidative damage.

PMID- 19761042
TI  - Anti-inflammatory, immunomodulatory and antinociceptive activity of Terminalia
      arjuna Roxb bark powder in mice and rats.
AB  - Terminalia arjuna back powder (400 mg/kg, po) significantly reduced formalin
      indued paw oedema at 24 h but not carrageenan-induced paw oedema. It
      significantly increased the anti-SRBC antibody titre in the secondary phase of
      immune response. The same dose significantly reduced the duration of licks and
      bites in both phases of formalin-induced pain response and showed significant
      increase in tail flick latency at higher dose (800 mg/kg, po). These effects of
      T. arjuna were antagonised by pretreatment with naloxone (1 mg/kg, ip). In
      another series of experiments, mice pretreated with morphine for three days in
      increasing doses (10, 15, 20 mg/kg, ip; twice daily) showed a decreased response
      in antinociceptive activity of morphine (5 mg/kg, ip). Further, cross tolerance
      was observed with T. arjuna (800 mg/kg, po) in morphine tolerant animals. These
      findings support the hypothesis that T. arjuna has anti-inflammatory potential
      against some phlogistic agents along with some immunomodulatory activity and also
      has antinococeptive action probably mediated via central opioid receptors.

PMID- 19761043
TI  - Antioxidant and hepatoprotective activities of Ocimum basilicum Linn. and
      Trigonella foenum-graecum Linn. against H2O2 and CCL4 induced hepatotoxicity in
      goat liver.
AB  - Significant hepatoprotective effects were obtained by ethanolic extract of leaves
      of O. basilicum and T. foenum-graecum against liver damage induced by H2O2 and
      CCl4 as evidenced by decreased levels of antioxidant enzymes (enzymatic and non
      enzymatic). The extract also showed significant anti lipid peroxidation effects
      in vitro, besides exhibiting significant activity in superoxide radical and
      nitric oxide radical scavenging, indicating their potent antioxidant effects.

PMID- 19761044
TI  - Mutation of Alternaria tenuissima FCBP-252 for hyper-active alpha-amylase.
AB  - Production of extracellular alpha-amylase enzyme by a filamentous fungus,
      Alternaria tenuissima was studied in solid-state fermentation (SSF) as well as
      submerged fermentation (SmF). The potential strain was successfully mutated by UV
      and ethyl methanesulfonate (EMS). High-level of alpha-amylase activity was
      obtained by the mutant At-Ch-5.6 (76.75 Units mL(-1)) after chemical treatment
      followed by UV mutant At-UV-2.8 (63.12 Units mL(-1)) which was significantly
      higher than parental A. tenuissima FCBP-252 (32 Units mL(-1)). These mutants with
      high levels of activity were genetically characterized using RAPD-PCR. Expression
      pattern of mutants exhibited that the mutants were isogenic variants of parent
      strain and out-performance of the mutants could be attributed to change in
      genetic make up. This work represented the first report of strain improvement in
      Alternaria for hyper activity of alpha-amylase enzyme and suggested that this
      fungus could be used to extract purified enzyme.

PMID- 19761045
TI  - Physical mapping of rRNA gene in endangered fish Osteobrama belangeri
      (Valenciennes, 1844) (family: Cyprinidae).
AB  - Physical mapping of the 18S ribosomal RNA gene (rDNA) was carried out by
      fluorescent in situ hybridization (FISH) in the endangered freshwater fish O.
      belangeri. The specimens were collected from Imphal valley, Manipur, India and
      metaphase chromosome preparation was made using standard hypotonic treatment,
      methanol-acetic acid fixation and flame-drying technique followed by Giemsa,
      silver, CMA3 staining for complete cytogenetic characterization of the species.
      The diploid chromosome number was found to be 50 and the karyotype composed of
      6m+16sm+12st+16t (FN=72). One active rDNA site, located on short arm of 3rd
      submetacentric chromosome, was mapped by FISH and confirmed by silver and CMA3
      staining. The karyomorphology, chromosomal location of rDNA loci in this species
      and the utility of these cytogenetic markers have been discussed in the paper.

PMID- 19761046
TI  - Protective potentials of a plant extract (Lycopodium clavatum) on mice
      chronically fed hepato-carcinogens.
AB  - Chronic feeding of carcinogens p-dimethylamino azobenzene (initiator) and
      phenobarbital (promoter) for 90 and 120 days elevated activities of acid and
      alkaline phosphatases, levels of blood glucose and cortisol and decreased the
      activities of glutathione reductase, succinate dehydrogenase, and blood
      cholesterol and hemoglobin contents, and levels of serum estradiol and
      testosterone in mice. Levels of these biomarkers in both liver and spleen tissues
      were positively altered along with a significant reduction of tumor incidence in
      liver of carcinogen intoxicated mice treated with spore extract of Lycopodium
      clavatum. The results validate the use of this plant extract in complementary and
      alternative medicines against hepato-toxicity.

PMID- 19761048
TI  - Abstracts of the 21st American Peptide Symposium, June 7-12, 2009, Bloomington,
      Indiana, USA.

PMID- 19761047
TI  - Effect of alpha-tocopherol supplementation on renal oxidative stress and Na+/K+ 
      adenosine triphosphatase in ethanol treated Wistar rats.
AB  - Ethanol intoxication resulted in high extent of lipid peroxidation, and reduction
      in antioxidant defenses (decreased GSH, GSH/GSSG ratio, and catalase, SOD and GPx
      activities) and (Na+/K+)-ATPase activity in kidney. Alpha-tocopherol treatment
      effectively protected kidney from ethanol induced oxidative challenge and
      improved renal (Na+/K+)-ATPase activity. Ethanol induced oxidative stress in the
      kidney and decreased (Na+/K+)-ATPase activity could be reversed by treatment with
      ascorbic acid.

PMID- 19761049
TI  - Abstracts of the 44th Annual Congress of the Canadian Neurological Sciences
      Federation. June 9-12, 2009, Halifax, Nova Scotia, Canada.

PMID- 19761050
TI  - Abstracts of EuroPCR 2009, May 25-28, 2010, Paris, France.

PMID- 19761051
TI  - Proceedings of the 33rd National Congress of the Italian Society of
      Histochemistry, June 8-10, 2009, Rome, Italy.

PMID- 19761052
TI  - Abstracts of the NASPSPA (North American Society for the Psychology of Sport and
      Physical Activity) 2009 Conference, June 11-13, 2009, Austin, Texas, USA.

PMID- 19761054
TI  - Good manufacturing practices should not be "skin deep".

PMID- 19761055
TI  - [Proceedings of the XV Argentine Congress of Hepatology. June 25-28, 2009. Buenos
      Aires, Argentina].

PMID- 19761056
TI  - Researchers shoot selves in foot - St. John's Wort ineffective cure for bloody
      foot.

PMID- 19761057
TI  - Abstracts from the XL Nordic Meeting of Gastroenterology, June 8-11, 2009,
      Stavanger, Norway.

PMID- 19761059
TI  - Abstracts from the Annual Meeting of the German Society for Cell Biology. March
      24-27, 2009, Konstanz, Germany.

PMID- 19761058
TI  - The time for environmental medicine is NOW!

PMID- 19761060
TI  - Abstract from the 7th Western Vascular Institute Symposium. May 21-22, 2009.

PMID- 19761061
TI  - Proteomics. Methods and protocols. Preface.

PMID- 19761062
TI  - [Remembering Gyorgy Fenyes (1924-1998)].

PMID- 19761063
TI  - Will the stork return to Europe and Japan? Understanding fertility within
      developed nations.

PMID- 19761064
TI  - [Clinical case. Keratocyst of the maxilla sinus].

PMID- 19761065
TI  - The compleat oncologist.

PMID- 19761066
TI  - Recommendation preoperative 5-FU/RT fir T1-3, N0 disease.

PMID- 19761067
TI  - Cancer-related fatigue. Clinical practice guidelines in oncology.
AB  - These guidelines propose a treatment algorithm in which patients are evaluated
      regularly for fatigue using a brief screening instrument, and are treated as
      indicated by their fatigue level. The algorithm's goal is to identify and treat
      all patients with fatigue that causes distress or interferes with their daily
      activities or functioning. Management of fatigue begins with primary oncology
      team members who perform the initial screening and either provide basic education
      and counseling or expand the initial screening to a more focused evaluation for
      moderate or higher levels of fatigue. At this point the patient is assessed for
      current disease and treatment status, a review of body systems, and an in-depth
      fatigue evaluation. In addition, the patient is assessed for the presence of
      seven treatable factors known to contribute to fatigue: pain, emotional distress,
      sleep disturbance, anemia, alterations in nutrition, deconditioning, and
      comorbidities. If any of these conditions are present, they should be treated
      according to practice guidelines, with referral to other care professionals as
      appropriate, and the patient's fatigue should be reevaluated regularly. If none
      of the seven factors are present or the fatigue is unresolved, selection of
      appropriate fatigue management and treatment strategies is considered within the
      context of the patient's clinical status: receiving active cancer treatment,
      receiving disease-free long-term follow-up, or receiving care at the end of life.
      Management of fatigue is cause-specific when conditions known to cause fatigue
      can be identified and treated. When specific causes, such as infection, fluid and
      electrolyte imbalances, or cardiac dysfunction, cannot be identified and
      corrected, nonpharmacologic and pharmacologic treatment of the fatigue should be
      considered. Nonpharmacologic interventions may include a moderate exercise
      program to improve functional capacity and activity tolerance, psychosocial
      programs to manage stress and increase support, restorative therapies to decrease
      cognitive alterations and improve mood state, and nutritional and sleep
      interventions for patients with disturbances in eating or sleeping. Pharmacologic
      therapy may include drugs, such as antidepressants for depression or
      erythropoietin for anemia. A few clinical reports of the use of psychostimulants
      suggest the need for further research on these agents as potential treatment
      modalities in managing fatigue. Effective management of cancer-related fatigue
      involves an informed and supportive oncology care team that assesses patients'
      fatigue levels regularly and systematically, educates and counsels patients
      regarding strategies for coping with fatigue, and uses institutional fatigue
      management experts for referral of patients with unresolved fatigue.

PMID- 19761068
TI  - A cancer-related fatigue clinic: opportunities and challenges.
AB  - Cancer-related fatigue (CRF) is the most prevalent symptom of cancer, occurring
      in 60% to 90% of patients and surpassing pain in frequency. CRF may increase
      patients' anxieties and hamper their quality of life. We developed a CRF clinic
      in 1998 because we believed there needed to be a more focused effort on the
      education, evaluation, and treatment of CRF for our patients. Since then, we have
      gained clinical insights into the planning, development, and evolution of this
      endeavor. Our objective is to share our experiences and provide preliminary
      analysis of the first 123 patients evaluated in this clinic.

PMID- 19761069
TI  - Distress management. Clinical practice guidelines.
AB  - The evaluation and treatment model expressed in the NCCN Distress Management
      Guidelines recommends that each new patient be rapidly assessed in the office or
      clinic waiting room for evidence of distress using a brief screening tool (the
      Distress Thermometer and Problem List) presented in Figure 1 (see page 369). A
      score of 5 or greater on the thermometer should trigger further evaluation and
      referral to a psychosocial service. The choice of which service should be
      determined by the problem areas specified on the Problem List. Patients with
      practical and psychosocial problems are referred to social work, emotional or
      psychological (excessive sadness, worry, nervousness) problems to mental health,
      and spiritual concerns to pastoral counselors. The primary oncology team members-
      doctor, nurse, and social worker--are central to making this model work. Team
      members collect information from the brief screening and problem list and expand
      it with the clinical evaluation. It is critical for at least one team member to
      be familiar with the mental health, psychosocial, and pastoral counseling
      resources available in the institution and the community. A list of the names and
      phone numbers for these resources should be kept in all oncology clinics and
      updated frequently. The first step in implementing this model is to establish a
      multidisciplinary committee in each institution or office responsible for 1)
      revising and modifying the standards of care to fit the particular clinical care
      setting and 2) implementing and monitoring the use of these standards. Because
      each institution has its own culture, standards must be implemented in ways that
      are compatible with each institution. The second step is to institute
      professional educational programs to ensure that staff is 1) aware that distress
      is under-recognized, 2) knowledgeable about the management of distress, and 3)
      aware of the resources available to treat it. It is important to have access to
      mental health professionals and clergy who are trained to deal with cancer
      related distress. The benefits of treating distress in cancer accrue to the
      patients and their families, to the treating staff, and to improved efficiencies
      in clinic operations. Health care contracts often allow these services to "fall
      through the cracks" by failing to reimburse for them through either behavioral
      health or medical insurance. Reimbursement for services to treat psychosocial
      distress must be included in medical health care contracts to prevent
      fragmentation of services for the medically ill. For patients with cancer,
      integration, not separation, of mental health services and medical services is
      critically important. Also outcomes research studies that include quality-of-life
      assessment and analysis of cost-effectiveness are needed. Patients and families
      should be informed that management of distress is part of their total medical
      care. Finally, the multidisciplinary committee, office practice, or institution
      must be responsible for evaluating the quality of the distress management (see
      guidelines algorithm [page 368]), with CQI studies making an important
      contribution. Presently, the quality of the psychological care patients receive
      is not routinely monitored. Accrediting bodies have not directly examined the
      quality of psychosocial care, nor have they established minimal performance
      standards for its delivery. The panel believes that psychosocial care should and
      will eventually be on our institution's report cards.

PMID- 19761070
TI  - Mental illness stigma as a barrier to psychosocial services for cancer patients.
AB  - Empirically validated psychosocial interventions have been shown to improve
      adjustment and coping among cancer patients. Therefore, an emerging standard of
      practice is to integrate supportive services for cancer patients into the medical
      management of the disease. However, unanticipated barriers may negatively
      influence receptivity to psychosocial services. For example, among the general
      population, two-thirds of individuals in need of psychiatric services do not
      receive them. Numerous barriers have been reported that interfere with receipt of
      mental health services among members of the general population. In addition to
      access issues, stigma associated with mental illness and its treatment represents
      a significant barrier to care. Stigma associated with mental illness and mental
      health services use is an under-researched barrier to the effective management of
      the psychosocial sequelae of a cancer diagnosis and treatment. This article
      reviews the relevant literature on mental health stigma and makes recommendations
      for increasing access to psychosocial services for cancer patients and their
      families.

PMID- 19761071
TI  - Psychological issues in geriatric oncology.
AB  - Optimism about improved survival from cancer has increased. However, even with
      tremendous improvements in screening techniques and treatment, a cancer diagnosis
      may shatter the dream of a dignified old age for elderly patients. Cancer
      diagnosis and treatment often produce psychological stresses resulting from the
      actual symptoms of the disease, as well as the patient and family's perceptions
      of the disease and its stigma. Concerns related to cancer have particular meaning
      for aging individuals who undergo these situations in the context of retirement,
      widowhood, other medical disabilities, and other losses. Today, patients and
      families are more interested in treatment issues and quality of life, both during
      and after treatment. In this article we discuss late life depression, anxiety,
      and delirium and treatments related to elderly patients coping with cancer.

PMID- 19761072
TI  - Palliative care. Clinical practice guidelines in oncology.

PMID- 19761073
TI  - Seeking drug treatment for OxyContin abuse: a chart review of consecutive
      admissions to a substance abuse treatment facility in Kentucky.
AB  - The abuse of prescription opioids has been reported to be on the rise and has
      gained much public attention, especially given the recent media coverage devoted
      to the abuse of sustained-release oxycodone (OxyContin, Purdue Pharma LP,
      Stamford, CT). We tracked admissions to our substance abuse program to put
      OxyContin abuse into perspective as a presenting problem in the region. A total
      of 258 admissions to a psychiatric facility for opioid dependence over a 15 month
      period, for the treatment of prescription opioid abuse, were examined in this
      chart-review study. A total of 162 patients (62.8%) were admitted for problems
      related to OxyContin, and the remaining 96 (37.2%) were admitted for abusing
      other prescription opioids (not including OxyContin). Those abusing OxyContin
      were found to be younger, more often from a rural background, and more likely to
      be male compared with those abusing other prescription opioids. In addition, more
      than half met the criteria for an additional chemical dependency diagnosis and
      had an additional psychiatric diagnosis. Polysubstance abuse, including OxyContin
      abuse, was a significant presenting problem to our Addictive Disease Unit between
      October 2000 and December 2001. Although this chart-review study is not designed
      to be indicative of the epidemiology of OxyContin abuse, it offers some insight
      into the nature of this phenomenon in a particular region during the height of
      public attention paid to it. A follow-up prospective study to examine this
      phenomenon in multiple regions, further away chronologically from the increased
      media attention, is underway.

PMID- 19761074
TI  - Philosophical oncology: calling on the principle of double effect.
AB  - Reasonable human behavior is based on doing something for a consequence that is
      perceived as good. Ethical medical decision-making is based on prioritizing
      values after understanding the relevant facts. There is an ethical obligation to
      do no harm. This is especially true in relieving the pain and suffering of dying
      patients; in these cases, treatment has the risk of contributing to a patient's
      death. The principle of double effect has been helpful as a moral guide in
      troubling cases to discern what actions are acceptable, even though the action
      could lead to an end that would seem as immoral as if the effect were directly
      intended. This principle, though, is not without problems and critics, and some
      have pointed out its shortcomings as an ethical guide.

PMID- 19761075
TI  - Assessment of pain caused by invasive procedures in cancer patients.
AB  - Invasive procedures are commonly required in the diagnosis and management of
      cancer in adults. However, little is known regarding the prevalence and severity
      of procedure-related pain in this patient population. This prospective study was
      conducted to determine the frequency and types of invasive procedures performed
      in a large comprehensive cancer center, the intensity of pain associated with
      these procedures, the types of periprocedural analgesics administered, and how
      these patients would like their procedural pain to be managed in the future.
      During a 6-week period, 102 cancer patients were interviewed immediately after
      undergoing an invasive procedure. They were asked to rate the pain they
      experienced before, during, and after their procedure using a verbal descriptor
      scale (VDS) ranging from 0 to 10. They also were asked if they would want more,
      less, or the same amount of pain medication if they were to undergo the same
      procedure again. The most frequently performed procedures were bone marrow
      aspirates and biopsies (68%), lumbar punctures (14%), and placements of central
      venous catheters (10%). The average pain rating during these procedures was 4.2
      (standard deviation [SD], 3.0). However, 26% of patients experienced severe pain
      (VDS score > or = 7) during the procedures. Twenty-four percent of patients
      surveyed received conscious sedation for their procedure. There was no
      statistical relationship between patients' pain ratings and their satisfaction
      with the pain control they received during the procedures. This study represents
      the largest descriptive study of procedural pain in adult cancer patients. As
      more than 50% of these patients experienced moderate to severe pain during
      procedures, further studies are needed to improve the control of procedure
      related pain in patients with cancer.

PMID- 19761076
TI  - Myelotoxicity and dose intensity of chemotherapy: reporting practices from
      randomized clinical trials.
AB  - Delivery of cancer chemotherapy is often limited by myelotoxicity, primarily
      neutropenia. As part of an effort to create a model to predict the risk of
      chemotherapy-induced neutropenia, we reviewed the reports of randomized clinical
      trials with more than 50 patients per arm in early-stage breast cancer (ESBC) and
      non-Hodgkin's lymphoma (NHL) published between 1990 and 2000. We observed that no
      hematologic toxicity data were reported in 39% and 34% of the ESBC and NHLtrials,
      respectively. The remaining trials reported on hematologic toxicity in 16
      different ways. When reported, rates of neutropenia, leukopenia, and
      hematotoxicity varied widely with the same and similar chemotherapy regimens.
      Dose-intensity data were not reported in 39% and 54% of ESBC and NHL trials,
      respectively. The majority of the remaining studies reported incomplete dose
      intensity data such as percentages of patients completing all cycles or receiving
      a given percentage of planned dose intensity. Only 28% reported the mean or
      median relative dose intensity received by patients. Based on this review, we
      conclude that current practices for reporting chemotherapy treatments are
      inadequate for describing the risk of chemotherapy to patients or for
      quantitatively assessing the risk of treatment alternatives. We recommend that
      standard procedures for documenting and reporting hematologic toxicity and dose
      intensity in cancer chemotherapy trials be required for publication of
      chemotherapy trials.

PMID- 19761077
TI  - Addressing social exclusion: analyses from South Asia and southern Africa.

PMID- 19761078
TI  - Relationships of exclusion and cohesion with health: the case of Bangladesh.
AB  - The concept of social exclusion, applied widely in the European Union, has in
      recent years been gaining use in Bangladesh, mostly by international development
      agencies. Does this discourse of deprivation, developed in the welfare states of
      northern Europe, have salience in its application to deprivation in countries
      like Bangladesh where, for example, 31% of the rural population lives in chronic
      poverty? The concept of social exclusion has three principal components: a
      dynamic and relational perspective which requires the identification of who or
      what causes exclusion; an explicit recognition of multiple dimensions of
      deprivation; and a longitudinal perspective, recognizing that individuals and
      groups are dynamic intra- and intergenerationally. The Social Exclusion Knowledge
      Network of the World Health Organization Commission on Social Determinants of
      Health expanded the concept to include health status as a contributor to and an
      outcome of exclusion and to show that actors beyond the state or public sector
      can critically impact exclusionary processes. In the Bangladesh application, the
      relevance of the modified model was explored to find that while there are
      negative associations between social exclusion and health status, much stronger
      documentation is needed of the relationship. The modification of including
      multiple sectors, such as private enterprise and civil society, in addition to
      the state, as having potential to impact exclusionary processes is fundamental to
      the application of the social exclusion model in Bangladesh.

PMID- 19761079
TI  - Living on the extreme margin: social exclusion of the transgender population
      (hijra) in Bangladesh.
AB  - The transgender people (hijra), who claim to be neither male nor female, are
      socially excluded in Bangladesh. This paper describes social exclusion of hijra
      [The term is used in this abstract both in singular and plural sense] focusing on
      the pathway between exclusion and sexual health. In an ethnographic study, 50 in
      depth interviews with hijra, 20 key-informant interviews, and 10 focus-group
      discussions (FGDs), along with extensive field observations, were conducted. The
      findings revealed that hijra are located at the extreme margin of exclusion
      having no sociopolitical space where a hijra can lead life of a human being with
      dignity. Their deprivations are grounded in non-recognition as a separate
      gendered human being beyond the male-female dichotomy. Being outside this norm
      has prevented them from positioning themselves in greater society with human
      potential and security. They are physically, verbally, and sexually abused.
      Extreme social exclusion diminishes self-esteem and sense of social
      responsibility. Before safer sex interventions can be effective in a broader
      scale, hijra need to be recognized as having a space on society's gender
      continuum. Hijra, as the citizens of Bangladesh and part of society's diversity,
      have gender, sexual and citizenship rights, that need to be protected.

PMID- 19761080
TI  - Homeless in Dhaka: violence, sexual harassment, and drug-abuse.
AB  - Bangladesh has experienced one of the highest urban population growth rates
      (around 7% per year) over the past three decades. Dhaka, the capital city,
      attracts approximately 320,000 migrants from rural areas every year. The city is
      unable to provide shelter, food, education, healthcare, and employment for its
      rapidly-expanding population. An estimated 3.4 million people live in the
      overcrowded slums of Dhaka, and many more live in public spaces lacking the most
      basic shelter. While a small but growing body of research describes the lives of
      people who live in urban informal settlements or slums, very little research
      describes the population with no housing at all. Anecdotally, the homeless
      population in Dhaka is known to face extortion, erratic unemployment, exposure to
      violence, and sexual harassment and to engage in high-risk behaviours. However,
      this has not been systematically documented. This cross-sectional, descriptive
      study was conducted to better understand the challenges in the lives of the
      homeless population in 11 areas of Dhaka during a 13-month period from June 2007
      to June 2008. A modified cluster-sampling method was used for selecting 32
      clusters of 14 female and male respondents, for a sample of 896. In addition to
      sociodemographic details, this paper focuses specifically on violence, drug
      abuse, and sexual harassment. The findings showed that physical assaults among
      the homeless, particularly among women, were a regular phenomenon. Eighty-three
      percent of female respondents (n=372) were assaulted by their husbands, station
      masters, and male police officers. They were subjected to lewd gestures,
      unwelcome advances, and rape. Male respondents reported being physically
      assaulted while trying to collect food, fighting over space, or while stealing,
      by police officers, miscreants, or other homeless people. Sixty-nine percent of
      the male respondents (n=309) used locally-available drugs, such as marijuana and
      heroin, and two-thirds of injecting drug-users shared needles. The study
      determined that the homeless are not highly mobile but tend to congregate in
      clusters night after night. Income-generating activities, targeted education,
      gender-friendly community police programmes, shelters and crises centres, and
      greater community involvement are suggested as policy and programmatic
      interventions to raise the quality of life of this population. In addition, there
      is a need to reduce high rates of urban migration, a priority for Bangladesh.

PMID- 19761081
TI  - Does level of social capital predict perceived health in a community?--A study of
      adult residents of low-income areas of Francistown, Botswana.
AB  - This study explores and describes the relationships among neighbourhood
      characteristics, social capital, and health outcomes among low-income urban
      residents in Francistown, Botswana. Using an explanatory correlational research
      design to explore the relationships among the study variables, data were
      collected from 388 low-income urban residents in Francistown, Botswana. The study
      further examined the role of social capital on the environmental quality for the
      overall health and quality of life and the psychological, physical and level of
      independence domains of health. Several studies have explored these relationships
      but currently no study has explored this relationship in Africa and Botswana in
      particular. Selected concepts from social capital theory and stress theory were
      used as a conceptual framework. Using linear and multiple regression models,
      results of the study showed that social capital did not correlate with the
      overall health and quality of life and the level of independence domain of health
      but positively correlated with psychological well-being. Social capital
      negatively predicted physical health. Hierarchical moderated multiple-regression
      analyses were conducted to examine the moderating role of social capital. To the
      contrary, social capital did not moderate the effects of chronic community
      stressors on all health outcomes. Social capital, however, moderated the effects
      of the poor environmental quality on level of independence and physical health
      outcomes but not on the psychological and overall health and quality of life.
      These results underscore the importance of considering the role of social
      capital, especially in low-income communities.

PMID- 19761082
TI  - Paramedic-conducted mental health counselling for abused women in rural
      Bangladesh: an evaluation from the perspective of participants.
AB  - This paper reports on evaluation of an initiative to use paramedics as the first
      level mental health counsellors of abused women in rural Bangladesh (2003-2004)
      from the perspective of the abused women who participated in one or more
      counselling sessions. Thirty in-depth interviews, followed by a survey(n=372),
      targeted to cover all participants, were conducted in 2006. Overall, the
      arrangement, management of ethical issues, and skills of paramedics were rated
      favourably. Most (89%) abused women (n=372) considered the session useful; one
      fourth of these women considered it very useful; and only a few abused women
      considered the session useless. Usefulness of the session was expressed mostly in
      terms of relief attained after talking about the issue. Most (87%) women reported
      being encouraged to be self-confident. In a context characterized by low self
      confidence of women, lack of opportunity to talk about violence, and absence of
      professional mental health counselling services, this initiative is sufficiently
      promising to warrant further testing.

PMID- 19761083
TI  - Can social inclusion policies reduce health inequalities in sub-Saharan Africa?-
      A rapid policy appraisal.
AB  - The global resurgence of interest in the social determinants of health provides
      an opportunity for determined action on unacceptable and unjust health
      inequalities that exist within and between countries. This paper reviews three
      categories of social inclusion policies: cash-transfers; free social services;
      and specific institutional arrangements for programme integration in six selected
      countries--Botswana, Mozambique, South Africa, Ethiopia, Nigeria, and Zimbabwe.
      The policies were appraised as part of the Social Exclusion Knowledge Network
      (SEKN) set up under the auspices of the World Health Organization's Commission on
      Social Determinants of Health. The paper highlights the development landscape in
      sub-Saharan Africa and presents available indicators of the scale of inequity in
      the six countries. A summary of the policies appraised is presented, including
      whether or what the impact of these policies has been on health inequalities.
      Cross-cutting benefits include poverty alleviation, notably among vulnerable
      children and youths, improved economic opportunities for disadvantaged
      households, reduction in access barriers to social services, and improved
      nutrition intake. The impact of these benefits, and hence the policies, on health
      status can only be inferred. Among the policies reviewed, weaknesses or
      constraints were in design and implementation. The policy design weaknesses
      include targeting criteria, their enforcement and latent costs, inadequate
      participation of the community and failure to take the cultural context into
      account. A major weakness of most policies was the lack of a monitoring and
      evaluation system, with clear indicators that incorporate system responsiveness.
      The policy implementation weaknesses include uneven regional implementation with
      rural areas worst affected; inadequate or poor administrative and implementation
      capacity; insufficient resources; problems of fraud and corruption; and lack of
      involvement of civil servants, exacerbating implementation capacity problems. The
      key messages to sub-Saharan African governments include: health inequalities must
      be measured; social policies must be carefully designed and effectively
      implemented addressing the constraints identified; monitoring and evaluation
      systems need improvement; and participation of the community needs to be
      encouraged through conducive and enabling environments. There is a need for a
      strong movement by civil society to address health inequalities and to hold
      governments accountable for improved health and reduced health inequalities.

PMID- 19761084
TI  - Review of the Bangladesh female secondary school stipend project using a social
      exclusion framework.
AB  - The Female Secondary School Stipend Project in Bangladesh was established to
      increase the enrollment of girls in secondary schools, thereby delaying marriage
      and childbearing. This analysis examined the existing data using the social
      exclusion framework to clarify the primary exclusionary factors that have kept
      girls from education: harassment, poverty, and the primacy of marriage and
      childbirth and explored the extent to which the project has diminished such
      barriers. While causality is difficult to establish, data suggest that the
      stipend programme has contributed to the rise in enrollment of girls in secondary
      schools. Questions remain as to the impact of the stipend programme on delaying
      marriage, empowerment of girls and women, and enhancing employment opportunities.
      A thorough assessment of the impact is required. The case study suggests that, if
      the programme design had focused on the quality and content of education and the
      broader economic and social context, more opportunities would have been created
      for social and economic participation of girls.

PMID- 19761085
TI  - The group-lending model and social closure: microcredit, exclusion, and health in
      Bangladesh.
AB  - According to social exclusion theory, health risks are positively associated with
      involuntary social, economic, political and cultural exclusion from society. In
      this paper, a social exclusion framework has been used, and available literature
      on microcredit in Bangladesh has been reviewed to explore the available evidence
      on associations among microcredit, exclusion, and health outcomes. The paper
      addresses the question of whether participation in group-lending reduces health
      inequities through promoting social inclusion. The group-lending model of
      microcredit is a development intervention in which small-scale credit for income
      generation activities is provided to groups of individuals who do not have
      material collateral. The paper outlines four pathways through which microcredit
      can affect health status: financing care in the event of health emergencies;
      financing health inputs such as improved nutrition; as a platform for health
      education; and by increasing social capital through group meetings and mutual
      support. For many participants, the group-lending model of microcredit can
      mitigate exclusionary processes and lead to improvements in health for some; for
      others, it can worsen exclusionary processes which contribute to health
      disadvantage.

PMID- 19761086
TI  - Capability development among the ultra-poor in Bangladesh: a case study.
AB  - Microcredit is advocated as a development tool that has the potential to reduce
      poverty, empower participants, and improve health. Results of several studies
      have shown that the extreme poor, or the ultra-poor, often are unable to benefit
      from traditional microcredit programmes and can, as a result of taking a loan
      they cannot repay, sink deeper into economic and social poverty. This case study
      describes an intervention directed at enabling the ultra-poor rural populations
      to pull themselves out of poverty. The intervention integrates multiple
      components, including asset grants for income generation, skills training, a time
      bound monthly stipend for subsistence, social development and mobilization of
      local elite, and health support. Results of an evaluation showed that, after 18
      months, the programme positively impacted livelihood, economic, social and health
      status to the extent that 63% of households (n=5,000) maintained asset growth and
      joined (or intended to join) a regular microcredit programme. Impacts included
      improved income, improved food security, and improved health knowledge and
      behaviour. Applying a social exclusion framework to the intervention helps
      identify the different dynamic forces that can exclude or include the ultra-poor
      in Bangladesh in development interventions such as microcredit.

PMID- 19761087
TI  - Civil society, health, and social exclusion in Bangladesh.
AB  - Civil society has the potential to have a positive impact on social exclusion and
      health equity through active monitoring and increased accountability. This paper
      examines the role of civil society in Bangladesh to understand why this potential
      has not been realized. Looking at two models of civil society action
      participation in decentralized public-sector service provision and academic think
      tank data analysis-this analysis examines the barriers to positive civil society
      input into public policy decision-making. The role of non-governmental
      organizations, political, cultural and economic factors, and the influence of
      foreign bilateral and multilateral donors are considered. The paper concludes
      that, with a few exceptions, civil society in Bangladesh replicates the
      structural inequalities of society at large.

PMID- 19761088
TI  - Corporate social responsibility initiatives addressing social exclusion in
      Bangladesh.
AB  - The private sector is often seen as a driver of exclusionary processes rather
      than a partner in improving the health and welfare of socially-excluded
      populations. However, private-sector initiatives and partnerships- collectively
      labelled corporate social responsibility (CSR) initiatives-may be able to
      positively impact social status, earning potential, and access to services and
      resources for socially-excluded populations. This paper presents case studies of
      CSR projects in Bangladesh that are designed to reduce social exclusion among
      marginalized populations and explores whether CSR initiatives can increase
      economic and social capabilities to reduce exclusion. The examples provide
      snapshots of projects that (a) increase job-skills and employment opportunities
      for women, disabled women, and rehabilitated drug-users and (b) provide
      healthcare services to female workers and their communities. The CSR case studies
      cover a limited number of people but characteristics and practices replicable and
      scaleable across different industries, countries, and populations are identified.
      Common success factors from the case studies form the basis for recommendations
      to design and implement more CSR initiatives targeting socially-excluded groups.
      The analysis found that CSR has potential for positive and lasting impact on
      developing countries, especifically on socially-excluded populations. However,
      there is a need for additional monitoring and critical evaluation.

PMID- 19761089
TI  - Micro-insurance in Bangladesh: risk protection for the poor?
AB  - Health services and modem medicines are out of reach for over one billion people
      globally. Micro-insurance for health is one method to address unmet health needs.
      This case study used a social exclusion perspective to assess the health and
      poverty impact of micro-insurance for health in Bangladesh and contrasts this
      with several micro-insurance systems for health offered in India. Micro-insurance
      for health in Bangladesh targeted towards the poor and the ultra-poor provides
      basic healthcare at an affordable rate whereas the Indian micro-insurance schemes
      for health have been implemented across larger populations and include high-cost
      and low-frequency events. Results of analysis of the existing literature showed
      that micro-insurance for health as currently offered in Bangladesh increased
      access to, and use of, basic health services among excluded populations but did
      not reduce the likelihood that essential health-related costs would be a
      catastrophic expense for a marginalized household.

PMID- 19761090
TI  - Strategies to reduce exclusion among populations living in urban slum settlements
      in Bangladesh.
AB  - The health and rights of populations living in informal or slum settlements are
      key development issues of the twenty-first century. As of 2007, the majority of
      the world's population lives in urban areas. More than one billion of these
      people, or one in three city-dwellers, live in inadequate housing with no or a
      few basic resources. In Bangladesh, urban slum settlements tend to be located in
      low-lying, flood-prone, poorly-drained areas, having limited formal garbage
      disposal and minimal access to safe water and sanitation. These areas are
      severely crowded, with 4-5 people living in houses of just over 100 sq feet.
      These conditions of high density of population and poor sanitation exacerbate the
      spread of diseases. People living in these areas experience social, economic and
      political exclusion, which bars them from society's basic resources. This paper
      overviews policies and actions that impact the level of exclusion of people
      living in urban slum settlements in Bangladesh, with a focus on improving the
      health and rights of the urban poor. Despite some strategies adopted to ensure
      better access to water and health, overall, the country does not have a
      comprehensive policy for urban slum residents, and the situation remains bleak.

PMID- 19761091
TI  - HIV/AIDS interventions in Bangladesh: what can application of a social exclusion
      framework tell us?
AB  - Bangladesh has maintained a low HIV prevalence (of less than 1%) despite multiple
      risk factors. However, recent serological surveillance data have reported very
      high levels of HIV infection among a subgroup of male injecting drug-users
      (IDUs). This suggests that an HIV/AIDS epidemic could be imminent in Bangladesh.
      Although biomedical and behavioural change projects are important, they do not
      address the root causes of observed risky behaviours among 'high-risk' groups. In
      Bangladesh, these groups include sex workers, IDUs, males who have sex with
      males, and the transgender population-hijra-who are all excluded groups. Using a
      social exclusion framework, this paper analyzed existing literature on HIV in
      Bangladesh to identify social, economic and legal forces that heighten the
      vulnerability of such excluded groups to HIV/AIDS. It found that poverty and bias
      against women are major exclusionary factors. The paper presents areas for
      research and for policy action so that the social exclusion of high-risk groups
      can be reduced, their rights protected, and an HIV epidemic averted.

PMID- 19761092
TI  - Artificial production of radioactive elements 1934.

PMID- 19761093
TI  - Enhancement of image quality with a fast iterative scatter and beam hardening
      correction method for kV CBCT.
AB  - The problem of the enormous amount of scattered radiation in kV CBCT (kilo
      voltage cone beam computer tomography) is addressed. Scatter causes undesirable
      streak- and cup-artifacts and results in a quantitative inaccuracy of
      reconstructed CT numbers, so that an accurate dose calculation might be
      impossible. Image contrast is also significantly reduced. Therefore we checked
      whether an appropriate implementation of the fast iterative scatter correction
      algorithm we have developed for MV (mega voltage) CBCT reduces the scatter
      contribution in a kV CBCT as well. This scatter correction method is based on a
      superposition of pre-calculated Monte Carlo generated pencil beam scatter
      kernels. The algorithm requires only a system calibration by measuring
      homogeneous slab phantoms with known water-equivalent thicknesses. In this study
      we compare scatter corrected CBCT images of several phantoms to the fan beam CT
      images acquired with a reduced cone angle (a slice-thickness of 14 mm in the
      isocenter) at the same system. Additional measurements at a different CBCT system
      were made (different energy spectrum and phantom-to-detector distance) and a
      first order approach of a fast beam hardening correction will be introduced. The
      observed image quality of the scatter corrected CBCT images is comparable
      concerning resolution, noise and contrast-to-noise ratio to the images acquired
      in fan beam geometry. Compared to the CBCT without any corrections the contrast
      of the contrast-and-resolution phantom with scatter correction and additional
      beam hardening correction is improved by a factor of about 1.5. The reconstructed
      attenuation coefficients and the CT numbers of the scatter corrected CBCT images
      are close to the values of the images acquired in fan beam geometry for the most
      pronounced tissue types. Only for extreme dense tissue types like cortical bone
      we see a difference in CT numbers of 5.2%, which can be improved to 4.4% with the
      additional beam hardening correction. Cupping is reduced from 20% to 4% with
      scatter correction and 3% with an additional beam hardening correction. After 3
      iterations (small phantoms) and 6 to 7 iterations (large phantoms) the algorithm
      converges. Therefore the algorithm is very fast, that means 1.3 seconds per
      projection for 3 iterations on a standard PC.

PMID- 19761094
TI  - Analysis of the physical interactions of therapeutic proton beams in water with
      the use of Geant4 Monte Carlo calculations.
AB  - The processes that occur when protons traverse a medium are investigated
      theoretically for a full therapeutic range of energies [20 MeV, 220 MeV]. The
      investigation is undertaken using the Geant4 toolkit for water medium. The beam
      is simulated only inside the phantom, effects of beamline are included in the
      overall beam properties as lateral width and momentum bandwidth. Every energy
      deposition is catalogued according to the particle and the process that caused
      it. The catalogued depositions are analysed statistically. There are only few
      important processes such as proton ionisation and nuclear scattering
      (elastic/inelastic) that constitute the main features of the energy distribution.
      At the same time processes concerning electrons are used very often without
      obvious effect to the result. Such processes can be therefore approximated in the
      simulation codes in order to improve the performance of the code. Neutron
      depositions are most important before the Bragg peak, still they are by an order
      of magnitude smaller than those of protons. In the region behind the Bragg peak
      only a small number of neutrons is created in the simulation and their energy
      contribution through secondary protons is by orders smaller than the effect of
      proton-produced secondary protons within the Bragg peak. Hence, the effects of
      neutrons created in the calculation volume can be neglected.

PMID- 19761095
TI  - Quantitative myocardial perfusion PET combined with coronary anatomy derived from
      CT angiography: validation of a new fusion and visualisation software.
AB  - AIM: Dynamic perfusion PET offers a clinical relevant advantage over myocardial
      perfusion scintigraphy due to its ability to measure myocardial blood flow
      quantitatively. This leads to an improved detection of multivessel disease and
      the possibility to assess not only the culprit lesion but lower grade stenoses as
      well. For appropriate revascularization, perfusion defects must be matched to
      coronary lesions. It has been shown that image fusion of morphological and
      functional images is superior to side-by-side analysis. Still, software for
      quantitative perfusion PET combined with CT angiography is rare. In this paper we
      present a new software tool for image fusion and visualization of quantitative
      perfusion PET and coronary morphology derived from CT angiography. METHODS: In
      our software, a PET uptake image is used for manual co-registration. Co
      registration results are then applied to the functional data derived from
      compartment modelling. To evaluate the reproducibility of the manual co
      registration, we calculated the deviation between a series of manual co
      registrations performed on nine pairs of unregistered PET and CT datasets by five
      trained participants. Two dimensional transfer functions were used to highlight
      the coronary arteries from the CT study in the combined data sets. RESULTS: The
      average Euclidian distances for three references points were between 3.7 and 4.1
      mm. The maximum distance was 10.6 mm. By the use of the two dimensional transfer
      functions, coronary anatomy could be easily visualised either by user-interaction
      or automatically by use of neuronal networks. CONCLUSIONS: With this approach it
      is possible to combine quantitative perfusion PET with coronary anatomy derived
      from CT angiography. Our first experiences indicate that manual image fusion with
      our tool is reproducible and that visualisation of the combined datasets is
      achieved within short time.

PMID- 19761096
TI  - Experimental determination of the Stern layer thickness at the interface of the
      human arachnoid membrane and the cerebrospinal fluid.
AB  - The paper is part of an investigation of the electrostatic forces contributing to
      the interaction between colloidal molecules, suspended in the cerebrospinal
      fluid, with other molecules of the cerebrospinal fluid and with the surrounding
      environment. The study is based on experimental observations and theoretical
      considerations. We are reporting about the microscopic observation of particles
      suspended in the cerebrospinal fluid which was obtained by lumbar puncture of 27
      neurosurgery patients. We found that the mean particle diameter and therefore the
      mean thickness of the Stern layer at the interface of the arachnoid membrane with
      the cerebrospinal fluid is a few micrometers. Individual variations of this
      diameter have been observed.

PMID- 19761097
TI  - [Radiation exposure of staff during endovascular brachytherapy with Re-188 after
      PTA in the peripheral blood stream].
AB  - Endovascular brachytherapy using a balloon catheter filled with Re-188 solution
      is a promising method for the prophylaxis of restenosis in peripheral blood
      circulation after percutaneous transluminal angioplasty (PTA) treatments. Thereby
      about 20 GBq Re-188 with a specific activity of about 5 GBq/ml are used. The high
      ionisation density of the beta radiation with high energy leads to selective
      irradiation of the blood vessel wall near the catheter, whereas the surrounding
      tissue remains almost unaffected. However the hospital staff has to carry out
      some work steps within close range to the high activity during preparation and
      therapy, causing a high risk of skin exposure, in particular at the hands.
      Estimations and measurements of the maximal local skin dose were made with thin
      layered thermoluminescence dosimeters. It was assessed that the annual dose limit
      for skin of 500 mSv may be exceeded considerably when using conventional
      procedures and considering the expected number of 75 treatments per annum. By
      using the newly developed rhenium-188 application device "FlowMedical Application
      System" the exposure risk for the staff could be reduced drastically. The maximum
      skin dose of 76 mSv for the radiologist and of 50 mSv for the physicist was
      decreased to 2 mSv per treatment for both of them. Consequently, from the
      radiation protection point of view, the itm Rhenium-PTA is a safe method. Any
      exceeding of the dose limit can be prevented.

PMID- 19761098
TI  - Model selection for time-activity curves: the corrected Akaike information
      criterion and the F-test.
AB  - Data analysis often requires a multi model approach, i.e. the best model or
      models are selected from a well chosen set of candidate models and subsequent
      parameter inference is conducted. The selection of the model or models which are
      best supported by the data can be accomplished using various criteria. The
      present work focuses on the comparison of two approaches namely the corrected
      Akaike information criterion (AICc) and the F-test for sparse data sets, which
      are common in medical research. The selection of the true model and the
      determination of relevant pharmacokinetic parameters as the clearance, the volume
      of distribution and the mean residence time are examined using Monte Carlo
      simulations with 10000 replications. The data (N = 10 per replication) are
      generated from a sum of two exponentials, which parameters were determined by
      fitting to time-concentration data of 111In labelled anti-CD66 antibody in blood
      serum. Four different normal distributed multiplicative statistical errors (0.05,
      0.1, 0.15, 0.2) were examined. The set of candidate models consists of sums of up
      to 3 exponentials. Comparisons with two different model set sizes were conducted.
      All candidate models are fitted to the generated data and selected according to
      the AICc and the F-test. Both selection criteria perform well for our data. The
      selection frequency of functions of lower dimension increases proportionally to
      the statistical error for both criteria, while for higher errors, the AICc tends
      to choose a model of lower dimension more frequently than the F-test. In
      addition, the overfitted fraction decreases proportionally to the statistical
      error for both methods but selection frequency of function of higher dimension is
      larger using the F-test. The choice of the adequate model set is important for
      the positive effect of model averaging concerning the bias and the variability of
      the estimated parameters. It is in general assumed and has been confirmed in this
      study that parameter estimation using the AICc has clear advantages over the F
      test.

PMID- 19761099
TI  - [The GOSPEL study].

PMID- 19761100
TI  - [Inotrope therapy in acute heart failure: a critical review of clinical and
      scientific evidence for levosimendan in the context of traditional treatment].
AB  - The clinical heterogeneity of acute heart failure and the low number of
      controlled trials, to date, are the main causes of the lack of agreement on
      therapeutic objectives, uncertainty on the most appropriate management, and
      difficulties to obtain robust evidence for the treatment of this syndrome. The
      inappropriate use of inotropic agents is one the most common pitfalls shown by
      registries. Two to 10% of patients admitted for acute heart failure present with
      a low output syndrome, a clinical profile associated with high mortality, where
      inotropes may be a rational therapeutic choice. Crucial points for an effective
      use of inotropes are an accurate evaluation and selection of patients, tailoring
      of therapeutic schemes and strict patient monitoring. Beta-adrenergic agonists
      and phosphodiesterase inhibitors increase myocardial oxygen demand, favor
      arrhythmias and may cause peripheral vasodilation with a secondary decrease in
      coronary perfusion pressure. These effects may translate in myocardial ischemia,
      loss of cardiomyocytes and accelerated ventricular remodeling with worse
      prognosis. Levosimendan, a novel inotropic agent studied according to the
      principles of evidence-based medicine, augments myocardial contractility without
      changes in intracellular calcium concentrations, and with minimal impact on
      myocardial oxygen consumption. This paper, based on an expert consensus, aims to
      suggest criteria for the appropriate use of inotropic agents in acute heart
      failure, based on a critical appraisal of the existing evidence and clinical
      experience.

PMID- 19761101
TI  - [Drug therapy of type 2 diabetes and cardiovascular prevention: potentials for
      liraglutide].
AB  - Recently, the European Medicines Agency (EMEA) Committee for Medicinal Products
      for Human Use (CHMP) adopted a positive opinion, recommending to grant a
      marketing authorization for liraglutide for the treatment of type 2 diabetes
      mellitus. Liraglutide is the first human glucagon-like peptide-1 (GLP-1) analog,
      based on the structure of native GLP-1, with pharmacokinetic properties suitable
      for once-daily dosing. In the phase III Liraglutide Effect and Action in Diabetes
      (LEAD) program, liraglutide has been shown to lower glycated hemoglobin to the
      same extent or more than other antidiabetic drugs including insulin. Liraglutide
      determines favorable changes in the global cardiovascular risk profile because
      its use is associated with weight loss, blood pressure reduction, as well as
      improvements of several cardiovascular risk biomarkers. Liraglutide is generally
      well tolerated, the most frequently reported adverse effect is transient nausea,
      and it does not seems to have significant interactions with medications commonly
      used for cardiovascular prevention. This article reviews, for the practicing
      cardiologist, the results of the LEAD program and explores liraglutide potentials
      for cardiovascular prevention in type 2 diabetes mellitus.

PMID- 19761102
TI  - [Diabetic foot: a case of limb salvage].

PMID- 19761104
TI  - [European Society of Cardiology guidelines on ST-elevation myocardial infarction:
      what is new?].

PMID- 19761103
TI  - [Management of acute myocardial infarction in patients presenting with persistent
      ST-segment elevation].

PMID- 19761105
TI  - [Observation on changes of the intragastric protein phosphorylation level
      involving electroacupuncture-induced improvement of the injured gastric mucosa in
      the rat].
AB  - OBJECTIVE: To study the effect of electroacupuncture (EA) of Stomach Meridian
      acupoints on changes o of the related protein phosphorylation in the gastric
      mucosa involving the repair of the injured gastric mucosa in the rat. METHODS: A
      total of 20 SD rats were divided into control, model, acupoint and non-acupoint
      groups, with 5 cases in each. Gastric mucosa injury model was established by
      intragastric perfusion of dehydrated alcohol (0.8 ml/100 g). EA (4 Hz/50 Hz, 1-3
      mA) was applied to "Zusanli" (ST 36), "Liangmen" (ST 21) and "Sibai" (ST 2), and
      the corresponding non-acupoints, once daily for 7 days. Gastric mucosal ulcer
      index (UI) was measured, and the profiling of the protein phosphorylation of
      interest in gastric mucosa cells was detected by antibody microarrays. RESULTS:
      In comparison with control group, the gastric mucosal UI of model group was
      significantly higher than that of control group (P < 0.01), while the UI of EA
      group was significant lower than those of model group and non-acupoint group (P <
      0.01), suggesting a recovery of the injured mucous membrane. Findings of protein
      array analysis indicated that a total of 720 kinds of phosphorylated proteins (>
      or = 1.5 folds) were found in the injured gastric mucosa. Compared to model
      group, the phosphorylation levels of 100 and 20 proteins were up-regulated, and
      16 and 9 proteins down-regulated in acupoint and non-acupoint groups,
      respectively. The up-regulated proteins involve cell cycle mediation, cell
      proliferation, anti-apoptosis, and the regulation of the cell adhesion,
      cytoskeleton protein, inflammation, immune activities, etc. while the down
      regulated proteins involve the down-regulation of the phosphorylation levels of
      the apoptosis proteins, adhesion proteins and cytoskeleton proteins, etc. In
      comparison to non-acupoint group, the phosphorylation levels of 100 proteins were
      up-regulated and 16 proteins down-regulated in acupoint group. CONCLUSION: EA of
      acupoints of the Stomach Meridian can promote repair of the injured gastric
      mucosa, which may be related to its effects in regulating the levels of
      phosphorylation of many signaling proteins.

PMID- 19761106
TI  - [Effect of electroacupuncture on the behavior and the expression of amyloid beta
      protein, amyloid precursor protein and ChAT in APP 695 V 717 I transgenic mice].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) on the expression of
      amyloid precursor protein (APP) and amyloid beta-protein (Abeta) in hippocampal
      CA 1 area and cerebral cortex in APP 695 V717 I transgenic mice, so as to
      investigate its underlying mechanism in improving Alzheimer's disease (AD).
      METHODS: APP 695 V 717 I transgenic mice were randomly divided into model and EA
      groups, with 6 cases in each. The other 6 negatively-transgenic mice (C 57 BL/6
      J) were used as the normal control group. EA (2 Hz/100 Hz, 3 mA) was applied to
      "Baihui" (GV 20) and "Yongquan" (KI 1) for 15 min, once every other day for 3
      months. The learning-memory ability of mice was measured by Y-type maze test and
      the expression levels of APP, Abeta, and choline acetyltransferase (ChAT) in the
      cerebral cotex and hippocampal CA 1 area were detected by immunohistochemistry.
      RESULTS: In comparison with control group, the times of training for gaining
      correct reaction and the expression levels of Abeta and APP in both cerebral
      cortex and hippocampal CA 1 area in model group increased significantly (P <
      0.05, P < 0.01), while the expression level of ChAT of cerebral cortex in model
      group decreased considerably (P < 0.05). Compared to model group, +he times of
      training for gaining correct reaction and the expression levels of APP in both
      cerebral cortex and hippocampal CA 1 area, and Abeta in CA 1 area of EA group
      lowered remarkably (P < 0.05), while those of ChAT in cerebral cortex and
      hippocampal CA 1 area of EA group increased evidently (P < 0.05, P < 0.01).
      CONCLUSION: Electroacupuncture can improve the learning-memory capacity of the
      APP transgenic mice, which may be related to its effects in increasing the
      production of acetylcholine and lowering the levels of APP and Abeta in the
      brain.

PMID- 19761107
TI  - [Influence of electroacupuncture on the expression of cyclooxygenase mRNA and
      protein in rats with air-pouch plus recombinant human IL-1beta induced
      inflammation at the back].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) on changes of
      cyclooxygenase (COX)-2 mRNA and protein expression after inflammation occurrence
      at the back by application of human recombinant IL-1beta (hr IL-Ibeta) plus air
      pouch in rats, so as to analyze the relativity between EA-induced changes of COX
      2 expression and proinflammatory cytokines regulative pathway. METHODS: Ninety
      female Wistar rats were randomized into control, model, and EA groups with 30
      cases in each. Inflammatory model was established by subcutaneous implantation of
      a sterilized hollow teflon cylinder (sac, 1.5 mi in volume) at the back and
      intrasaccal injection of hr IL-1beta (10 ng/ml). EA (2 Hz, 1 mA) was immediately
      applied to "Quchi" (LI 11) for 30 min. Exudate in the sac was withdrawn at
      various intervals after hr IL-1beta-injection for assaying COX-2 mRNA expression
      with RT-PCR and protein expression with Western Blotting. RESULTS: In comparison
      with control group, one hour (h) after hr IL-1beta-injection, COX-2 mRNA and
      protein expression levels were up-regulated significantly in model group (P <
      0.01); while compared to model group, COX-2 mRNA and protein expression levels in
      EA group were down-regulated considerably (P < 0.05). 5 h and 24 h after hr IL
      1beta-injection, COX-2 mRNA expression in model and EA groups was significantly
      higher than that in control group (P < 0.01), and no significant differences were
      found between model and EA groups in COX-2 mRNA expression levels (P > 0.05). On
      the contrary, 5 h after administration of hr IL-1beta, COX-2 protein expression
      in model group was significantly higher than that in control group (P < 0.05). On
      the 24 h after hr Ibeta-1beta-injection, no significant differences were found in
      COX-2 protein expression levels among control, model and EA groups (P > 0.05).
      CONCLUSION: EA can effectively suppress hr IL-1beta-injection induced up
      regulation of COX-2 mRNA and protein expression in the rats, suggesting a close
      relativity between the regulation of proinflammatory cytokines and EA-induced
      inhibition of COX-2 mRNA and protein expression.

PMID- 19761108
TI  - [Effect of electroacupuncture on epileptic EEG and intracellular Ca2+ content in
      the hippocampus in epilepsy rats].
AB  - OBJECTIVE: To study the underlying mechanism of electroacupuncture (EA) in
      relieving epilepsy in pentylenetetrazole (PTZ)-induced epilepsy rats. METHODS:
      Twenty SD rats were randomly divided into normal control, model, EA, Nimodipine
      groups, with 5 cases in each. Epilepsy model was established by intraperitoneal
      injection of PTZ (32.0 mg/kg), once daily for 28 days. EA (100 Hz, 0.6 mA) was
      applied to "Baihui" (GV 20) and "Dazhui" (GV 14), once daily for 7 days. For
      Nimodipine group, the rats were given with nimodipine (0.25 mg/kg, i.p.), once
      daily for 7 days. Electroencephalogram (EEG) was recorded and the fluorescence
      intensity of Ca2+ of the hippocampus tissue sections was detected by laser
      scanning confocal microscope (LSCM) after incubation in artificial cerebrospinal
      fluid containing Flou-3/AM (10 micromol/L) and pluronic F-127 (5 microl).
      RESULTS: Compared with model group, the latencies of epileptic EEG seizure
      prolonged obviously (P < 0.05), and epileptic EEG seizure frequencies decreased
      significantly (P < 0.05) in EA and Nimodipine groups. The fluorescence intensity
      of intracellular Ca2+ in hippocampus tissue in model group was obviously higher
      than that in control group (P < 0.01). In comparison to model group, Ca2+ levels
      in EA and Nimodipine groups lowered considerably (P < 0.05, P < 0.01). No
      significant differences were found between EA and Nimodipine groups in the
      aforementioned 3 indexes (P > 0.05). CONCLUSION: EA has an obvious anti-epileptic
      effect, which may be closely related to its effect in downregulating the
      increased hippocampal Ca2+ level in PTZ-kindled epilepsy rats.

PMID- 19761109
TI  - [Effect of electroacupuncture on cerebral cortex ultrastructure in rats with
      cerebral ischemia-reperfusion injury].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Baihui" (GV 20)
      and "Dazhui" (GV 14) on the ultrastructure of cerebral cortex in rats with
      cerebral ischemia reperfusion (CI/R) injury. METHODS: Fifteen SD rats were
      equally randomized into sham-operation (sham), model and EA groups. CI/R model
      was established by right middle cerebral artery occlusion for 1 h and reperfusion
      for 24 h. EA (20 Hz/80 Hz, 1-3 mA) was applied to "Baihui" (GV 20) and "Dazhui"
      (GV 14) for 30 min. The ischemic cerebral cortex tissue was taken, fixed in 2.5%
      glutaral solution, embedded in araldite, cut into sections and stained for
      observing the ultrastructure changes of cortical pyramidal cells, astrocyte and
      blood brain barrier (BBB) under transmission electronic microscope. RESULTS: In
      sham group, the anatomical structure of the cerebral pyramidal cells was normal
      basically. In model group, the neuronal mitochondria and the capillary
      endothelium and the processes of the astrocyte got swelling, the mitochondrial
      cristae were broken, the capillary lumens became narrow or were blocked up. In EA
      group, the injury degree of the pyramidal cells, glial cells and BBB were
      lighter. CONCLUSION: EA can reduce ischemic injury of the cerebral cortical
      neurons and blood brain barrier in rats with CI/R injury.

PMID- 19761110
TI  - [Effects of electroacupuncture on c-fos expression in nucleus of the solitary
      tract and electrocardiogram ST(II) in myocardial ischemia rats].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Neiguan" (PC 6)
      and "Zusanli" (ST 36) on c-fos expression in the nucleus of the solitary tract
      (NTS)and ischemic electrocardiogram (ECG) in acute myocardial ischemia (AMI)
      rats, so as to study the role of NTS in EA-induced improvement of AMI. METHODS:
      Thirty-six male SD rats were randomly divided into control, model, ST 36, PC 6,
      "Pianli" (LI 6), and "Heyang" (BL 55) groups, with 6 cases in each. AMI model was
      established by intraperitoneal injection of Isoproterenol (5 mg/kg). EA (4 Hz/20
      Hz, 1 mA) was applied to PC 6, ST 36, LI 6 and BL 55 for 20 min separately. c-fos
      expression in the NTS was detected by immunohistochemistry and ECG-ST(II) was
      recorded before and after AMI and EA. RESULTS: (1) Compared to control group, ECG
      ST(II) of model group elevated significantly, while in comparison with model
      group, ECG-ST(II) values of ST 36 and PC 6 groups decreased significantly (P <
      0.01), suggesting an improvement of AMI after EA. No significant changes of ECG
      ST(II) were found in LI 6 and BL 55 groups (P > 0.05). (2) The number of fos
      immunoreaction (fos-IR) positive neurons in the NTS in ST 36 and PC 6 groups was
      significantly lower than that in model, LI 6 and BL 55 groups (P < 0.01).
      CONCLUSION: EA of PC 6 and ST 36 can improve ischemic ECG in AMI rats and NTS is
      one of the centers for integrating cardiac functional activity and information
      from EA of PC 6 and ST 36.

PMID- 19761111
TI  - [Influence of electroacupuncture on hippocampal somatostatin (SS) and SS mRNA
      expression in chronic stress-induced depression rats].
AB  - OBJECTIVE: To study the underlying mechanism of electroacupuncture (EA) in
      relieving depression. METHODS: A total of 30 Wistar rats were randomly divided
      into normal control group (n=10), model group (n=10) and EA group (n=10).
      Depression model was established by lonely raising and chronic unpredictable mild
      stress for 21 days. EA (2 Hz, 1 mA) was applied to "Baihui" (GV 20) and
      "Sanyinjiao" (SP 6) for 20 min, once daily for 14 days. The expression (option
      density) of hippocampal somatostatin (SS) and SS mRNA was detected by using
      immunohistochemistry and reversed transcription-polymerase chain reaction (RT
      PCR) techniques respectively. RESULTS: Compared to normal control group, the
      crossing movement and rearing movement times of open-field test, and sucrose
      consumption in model group decreased significantly (P < 0.01), and hippocampal SS
      and SS mRNA expressions were downregulated remarkably (P < 0.05). Compared to
      model group, the crossing movement and rearing movement times in EA group
      increased considerably (P < 0.01), and hippocampal SS and SS mRNA expressions
      were upregulated remarkably (P < 0.05). No significant difference was found
      between EA and normal control groups in SS and SS mRNA expression. CONCLUSION: EA
      can effectively improve depression rats' behavior activity and upregulate
      hippocampal SS and SS mRNA expression.

PMID- 19761112
TI  - [Effect of electroacupuncture of "Neiguan" (PC 6) on heart rate and plasma
      catecholamine contents in ventricular tachycardia rats].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Neiguan" (PC 6)
      on heart rate (HR) and plasma catecholamine (CA) levels in ventricular
      tachycardia (VT) rats. METHODS: A total of 50 SD rats were randomly divided into
      normal control, sham-operation (sham), model, EA-PC 6 and EA-LU 7 groups, with 10
      cases in each. VT model was established by intravenous injection of cesium
      chloride (CsCl) via femoral vein. Electrocardiogram (ECG) was recorded. EA (2
      Hz/15 Hz, 1 mA) was separately applied to bilateral "Neiguan" (PC 6) and "Lieque"
      (LU 7) for 5 minutes, followed by collecting blood samples for detecting plasma
      norepinephrine (NE) and epinephrine (E) levels with fluorometric method. RESULTS:
      In comparison with normal control group, plasma NE and E contents in model group
      increased apparently (P < 0.01). Compared with model group, HR and plasma NE and
      E contents of EA-PC 6 group reduced significantly (P < 0.01), while those of EA
      LU 7 had no apparent change (P > 0.05). CONCLUSION: EA of "Neiguan" (PC 6) can
      downregulate heart rate and plasma CA level in VT rats, which may contribute to
      its effect in relieving tachycardia.

PMID- 19761113
TI  - [Observation on the therapeutic effect of acupuncture treatment of autism
      children].
AB  - OBJECTIVE: To observe the therapeutic effect of acupuncture ("Jin's Sanzhen")
      treatment for autism patients with different severity. METHODS: A total of 202
      autism children were divided into treatment group (n=118) and control group
      (n=84) according to their parents' will. Autism children in the treatment group
      were treated with "Jin's Sanzhen" therapy [for example, Niesanzhen: the point 2
      cun superior to the ear tip, and those at the same level 1 cun apart on the left
      and right sides; Naosanzhen: Naohu (GV 17), bilateral Naokong (GB 19), etc.],
      while those of control group accepted special training: behavior education
      (cognition, speech, communication ability, life self-care ability, etc.) and
      sensory integration training. The treatment was given to the patients in both
      groups once per day, six times a week for 4 months. RESULTS: Of the 78 and 58
      severe patients in the treatment and control groups, 63 (80.8%) and4 (6.9%)
      experienced marked improvement, 9 (11.5%) and 33 (56.9%) experienced improvement,
      6 (7.7%) and 21 (36.2%) failed, with the effective rates being 92.3% and 63.8%
      respectively. Of the 118 and 84 patients in the treatment and control groups,
      after the treatment, the no symptoms, mild, moderate and severe cases were 12
      (10.2%) and 3 (3.6%), 56 (47.5%) and 25 (29.8%), 45 (38.1%) and 23 (27.4%), 5
      (4.2%) and 33 (39.3%), respectively. The total score of Childhood Autism Rating
      Scale of treatment group was significantly lower than that of control group after
      the treatment in severe cases (P < 0.01), showing a better therapeutic effect of
      the treatment group. CONCLUSION: "Jin's Sanzhen" therapy has a better therapeutic
      effect for improving the autism patients symptoms at different severity.

PMID- 19761114
TI  - [Randomized controlled study on ear-electroacupuncture treatment of endometriosis
      induced dysmenorrhea in patients].
AB  - OBJECTIVE: To observe the therapeutic effect of ear-electroacupuncture (Ear-EA)
      on dysmenorrhea in patients with endometriosis and to explore its underlying
      mechanism. METHODS: A total of 80 endometriosis patients were randomly and
      equally divided into ear-EA group and body-EA group. EA (50 Hz, 0.5-0.8 mA) was
      applied to auricular points (Uterus, Subcortex, Shenmen, Endocrine, etc.) and
      body acupoints [Tianshu (ST 25), Qihai (CV 6), Guanyuan (CV 4), Sanyinjiao (SP
      6), Diji (SP 8), Uterus (EX-CA 1), etc.] respectively for 30 min, once every
      other day for 3 months. Dysmenorrhea severity score (DSS) was assessed and plasma
      prostaglandin (PGE2) and 6-Keto-PGF1alpha levels detected by radioimmunoassay.
      RESULTS: Compared with pre-treatment, DSS lowered significantly during the 1st
      and 2nd menstrual cycle in body-EA group, and during the 1st, 2nd and 3rd
      menstruation in ear-EA group; and the DSS of ear-EA group during the 3rd
      menstruation was evidently lower than that of body-EA group (P < 0.05). During
      the 3rd menstrual onset after the treatment, plasma PGE2 contents in both groups
      decreased obviously (P < 0.01), and plasma 6-Keto-PGF1alpha, levels increased
      considerably in comparison with pre-treatment (P < 0.01). Comparison between two
      groups during the 3rd menstruation showed that plasma PGE2 level of ear-EA group
      was markedly lower than that of body-EA group, and 6-Keto-PGF1alpha, level of ear
      EA group was significantly higher than that of body-EA group (P < 0.05). No
      significant difference was found between two groups in clinical therapeutic
      effect (P > 0.05). CONCLUSION: Both ear-EA and body-EA can effectively relieve
      endometriosis-induced dysmenorrhea, and the former is superior to the later in
      reducing pain severity, which may be closely related to their effects in reducing
      plasma PGE2 and raising 6-Keto-PGF1alpha level.

PMID- 19761115
TI  - [Randomized controlled clinical trials for electro-spoon-needles treatment of
      motor dysfunction in cerebral infarction patients].
AB  - OBJECTIVE: To observe the therapeutic effect of spoon-needle cluster electrical
      stimulation of scalp-points for motor dysfunction of cerebral infarction (CI)
      patients, so as to analyze its superiority in the treatment of CI. METHODS: A
      total of 164 CI inpatients with motor disturbance were randomly divided into
      spoon-needle cluster (SNO) group (n=84) and filiform-needle cluster (FNC) group
      (n80). Multiple filiform needles were inserted into the Yu's 7 scalp-points
      (Parietal region, Antero-parietal region, etc.), and manipulated for a while,
      followed by 6 hours' retention of the needles. Multiple spoon needles were fixed
      to the same scalp-points and then these scalp-points were stimulated with
      electric pulse for 30 mm. The treatment was given once daily, 6 times a week and
      for 4 weeks. The therapeutic effect was assessed by Fugl-Meyer assessment scale,
      Barthel Index and clinical neural function-defect assessment respectively.
      RESULTS: Compared to pre-treatment, the scores of Fugl-Meyer assessment scale and
      daily-life ability assessment of both SNC and FNC groups increased significantly
      after the treatment (P < 0.01), and those of clinical neural function-defect
      assessment of these two groups lowered considerably (P < 0.01). No significant
      differences were found between two groups in these 3 indexes( P > 0.05). After
      the treatment, of the 84 and 80 cases in SNC and FNC groups, 0 and 3 were cured
      basically, 44 and 45 experienced a marked improvement, 35 and 27 had an
      improvement, 5 and 5 failed, respectively. CONCLUSION: Spoon-needle cluster
      electro-stirmilation can effectively improve Cl patients' motor dysfiziction and
      daily-life activity ability, and is comparable to the filiform-needle cluster
      stimulation in clinical therapeutic effect.

PMID- 19761116
TI  - [A visible meridian phenomenon: moxibustion-induced appearance of the belt
      vessel].

PMID- 19761117
TI  - [Review of literature on the specificity of therapeutic effects of acupoints on
      the basis of data mining].
AB  - The specificity of the therapeutic effect of acupoints is an important research
      subject in acu-moxibustion medicine, but is short of systematic and profound
      literature review by using modern science and technology. The modern data mining
      technique provides a new reliable technique or an approach for assessing the
      relative specificity of the acupoint efficacy from literature reviewing angle. In
      order to explore the basic regularities of the specificity of acupoint efficacy,
      a data-library of acu-moxibustion literature should be established first,
      followed by setting up a data analysis model for which the acupoint prescriptions
      are considered to be the basis, and by establishing a data mining methodological
      system.

PMID- 19761118
TI  - [Observation and analysis on the meridian-collateral running track-related
      anatomical structure in the human body].
AB  - In the present paper the authors analyze the anatomical structure of the meridian
      running track by using the dialectical thought and comprehensive analysis of the
      integrated Chinese and western medicine. It has been observed that the "Qi
      passages" of the 14 meridians of Chinese medicine are located in the connective
      tissue among the interspace of the muscles, etc. distributing longitudinally. The
      "Qi-passages" of the 15 Luomai (collaterals of the meridians) are located in the
      connective tissue among the interspace of the muscles, etc. distributing
      transversally, while those of the small branches of the meridian collaterals are
      located in the interspace mesenchyme of the muscle bundles distributing in the
      whole body. The "Qi-passages" of the tiny branches of the meridian collaterals
      are located in the mesenchyme of the intracellular space, such as the muscle
      fibers in the whole body. The authors hold that the so-called "Mai Qi" of the
      meridian-collaterals is the liquid-Qi flowing in the vertical and horizontal
      tissue interspaces. The "Qi-passage" of the meridian-collaterals of Chinese
      medicine is the pathway of the liquid-Qi of the tissue interspaces. The structure
      of the meridian-collaterals is the tissue interspace. The meridian-collateral
      system is a regulation-control system in the human body where the Qi-passages
      communicate with each other, and is, in fact, the protoplasm, the liquid-Qi
      circulating in the tissue interspaces.

PMID- 19761119
TI  - [Advances of studies on the underlying mechanism of acupuncture efficacies by
      using functional magnetic resonance imaging].
AB  - In the present paper the authors review recent progress in the study on the
      underlying mechanism of acupuncture effects by using functional magnetic
      resonance imaging (fMRI) from (1) fMRI imaging technology, (2) the meridian
      collateral system of Chinese medicine, (3) the factors affecting the therapeutic
      effect of acupuncture, (4) the mechanism underlying the efficacy of acupuncture
      treatment, (5) the experimental design methods for studying acupuncture by using
      fMRI, and (6) the methods for analyzing fMRI data. Research results show that
      fMRI technology is a new and useful approach for studying the underlying
      mechanism of acupuncture effect.

PMID- 19761120
TI  - [Review on the mechanism of joint application of acupuncture therapy and
      medication in clinical practice].
AB  - Acupuncture therapy combined with medication has been widely used in clinic
      practice in China and proved to be effective in the, treatment of many disorders.
      The authors of the present paper review researches on the underlying mechanism of
      joint application of acupuncture therapy and medication in recent decade from (1)
      neural regulation, (2) endocrine regulation, and (3) immunological regulation.
      After comprehensive analysis, the authors think that the mechanism underlying the
      enhanced clinical efficacy of acupuncture therapy combined with drugs may be
      closely associated with the following factors: (1) acupuncture stimulation of
      acupoints leads to changes of the drug concentration in the blood and/or in the
      target organ and, (2) the reactivity or sensitivity of the target organ tissues
      to the specifically effective drug elements is enhanced.

PMID- 19761121
TI  - Surveillance of endometrial pathologies, especially for endometrial cancer, of
      breast cancer patients under tamoxifen treatment.
AB  - Tamoxifen is the antihormonal treatment of choice for postmenopausal breast
      cancer patients with positive estrogen receptors. One of the most significant and
      deleterious side-effects of TAM treatment appears to be a proliferative effect on
      the endometrium, including endometrial cancer. Today no active screening for
      patients treated with tamoxifen other than routine annual gynecologic
      surveillance is recommended, however many investigators have recommended that
      those women should warrant closer gynecological surveillance for endometrial
      cancer during treatment, especially those with high-risk factors. This article
      evaluates the diagnostic flow chart for the surveillance of endometrial
      pathologies in tamoxifen-treated breast cancer patients, according to the
      literature and to the Committee Opinion of the Triveneto Directors of
      Gynecological and Obstetrical Departments (North-east Italy).

PMID- 19761122
TI  - Patterns of care in the initial management of women with ovarian cancer in
      Ontario.
AB  - BACKGROUND: To facilitate the planning of future resources for cancer services in
      Ontario, Cancer Care Ontario commissioned an evaluation of operative services
      delivered for ovarian cancers. The affected population was characterized in terms
      of age, location of residence, and SES. Operative care delivery was described in
      terms of inpatient verses outpatient access, LHIN of treatment, surgical
      specialist providing treatment, and specific operative procedures. The
      investigations and consults around the time of diagnosis are described. METHODS:
      Women with an incident diagnosis of an ovarian malignancy were identified from 1
      April 2003 to 31 March 2004 using the Ontario Cancer Registry. Record linkages
      were created to other provincial health databases such as the Ontario Health
      Insurance Plan. RESULTS: We report on 963 women with ovarian cancer. The
      incidence of disease was related to increasing age. Access to surgery correlated
      with the highest income quintile, urban residence and LHIN. Twenty-seven percent
      of women did not have surgery for their ovarian cancer. Women of younger age were
      more like to receive surgery for ovarian cancer. Use of a laparotomy for biopsy
      was most common in community hospital (40%). Lymphadenectomy rates were low
      overall; rates for gynecologic oncologists were 13.2%. All women were assessed by
      CXR. CT scan of abdomen and pelvis occurred in 77% of women. MRIs were done
      infrequently. Medical oncology were involved in 26.6% of the patients.
      CONCLUSIONS: These pilot data would be enhanced with further information such as
      comorbidity, treatment intent (palliative/curative), histology, grade and stage.
      However, there are clear referral patterns to academic centres which means a need
      for manpower and hospital resources to deal with this population.

PMID- 19761123
TI  - An attempt at conservative treatment in selected cases of type I endometrial
      carcinoma (stage I a/G1) in young women.
AB  - PURPOSE: The aim of the study was to evaluate an attempt of conservative
      treatment in selected cases of endometrial carcinoma Stage I A/type I in young
      women. MATERIALS AND METHODS: The study comprised five young nulliparous women
      aged 24-38 (30.8 +/- 4.2) with well-defined type I endometrial carcinoma Stage I
      A/G1. Diagnostic dilatation and curettage (D&C) in these women was performed.
      Biochemical hormonal studies comprised the assessment of estrone, estradiol,
      progesterone, prolactin in basal conditions, prolactin after a metoclopramide
      test and total testosterone. In the treatment phase estriol was given
      intravaginally. Additionally progesterone was applied for 12 days in the second
      phase of therapeutic cycles. Moreover the women were given ergocryptine and
      metformin. RESULTS: After six months of therapy and during two years of follow-up
      histopathological examinations of material obtained from D&C the endometrial
      pattern was normal and free of cancer cells. CONCLUSIONS: 1) In selected cases
      the conservative treatment of young women diagnosed with type I endometrial
      carcinoma Stage I A/G1 could be indicated. 2) Conservative pharmacological
      treatment of young women with well-defined endometrial carcinoma Stage I A/G1
      type I should be monitored with followup histopathological examinations of
      material obtained from D&C of the endometrium and assessment of concentrations of
      sex hormones in the serum. 3) This kind of therapy requires frequent and thorough
      gynecological and clinical follow-up.

PMID- 19761124
TI  - Clinicopathological implications of inactivation of RASSF1A in serous epithelial
      ovarian cancers.
AB  - OBJECTIVE: To investigate the frequency of promoter hypermethylation of RASSF1A
      gene in ovarian cancers and its correlations to gene expression and
      clinicopathological characters in the Chinese population. METHODS: In this study,
      we detected the frequency of promoter hypermethylation of the RASSF1A gene in 60
      patients with primary serous epithelial ovarian carcinomas (SEOCs) using
      Methylation-Specific PCR (MSP). The gene expression of mRNA and protein was
      examined by RT-PCR and Western blot. RESULTS: The frequency of promoter
      hypermethylation of RASSF1A in Chinese primary SEOCs was 53.3%, whereas promoter
      hypermethylation was not found in normal ovarian tissues and benign ovarian
      tissues. The expression of both mRNA and protein of RASSF1A was significantly
      down-regulated or lost in the methylated group than in nonmethylated group (p <
      0.05, respectively). SEOCs with Stage III, IV exhibited a higher frequency of
      RASSF1A promoter hypermethylation (70.4%, 81.8%) than those with Stage I or Stage
      II (16.7%, 20.0%, p < 0.05, respectively). Hypermethylation patterns in RASSF1A
      were more frequently detected in poorly differentiated SEOCs (78.6%) than in
      moderately differentiated (23.8%) or in well-differetiated SEOCs (27.3%, p <
      0.05, respectively). CONCLUSIONS: The high frequency of promoter hypermethylation
      of RASSF1A contributes to the gene expression in Chinese primary SEOCs. The
      inactivation of the RASSF1A gene due to hypermethylation in the promoter region
      might play a critical role in the pathogenesis of ovarian cancers.

PMID- 19761125
TI  - Ovarian carcinoma apparently confined to the ovaries--the accuracy of surgical
      staging in Israel.
AB  - BACKGROUND: In order to allot an ovarian malignancy to FIGO Stage I, in addition
      to abdominal exploration and the basic operation, it is also necessary to do
      peritoneal washings for cytological examination, random peritoneal biopsies
      (including diaphragmatic assessment) and omental and retroperitoneal lymph node
      assessment. OBJECTIVE: The aim of the study was to assess the accuracy of
      surgical staging of ovarian carcinoma classified as Stage I in Israel. METHODS:
      Included were all patients with histologically confirmed epithelial ovarian
      carcinoma (EOC) classified as Stage I in a data base of a nationwide incidence
      case control epidemiological study of ovarian carcinoma conducted in Israeli
      Jewish women during the period 1994-1999. Surgical staging data of these patients
      were retrieved from pathological reports, and from clinical records when
      available. RESULTS: A total of 182 EOC patients were classified as Stage I. About
      86% of the patients underwent hysterectomy and bilateral salpingo-oophorectomy.
      The most commonly performed staging procedure was omental assessment (85.2%)
      while peritoneal biopsy was the least common one (34.1%). In 17 (9.3%) of the
      patients none of the staging procedures were done and only 34 (18.7%) had optimal
      staging. CONCLUSION: Although the data are from a decade ago, they seem to
      indicate the need for an increased awareness of the necessity for accurate
      surgical staging of tumors apparently confined to the ovaries since it can
      identify a group of patients who require surgical therapy alone and who can be
      spared the complications, inconvenience and cost of adjuvant chemotherapy.

PMID- 19761126
TI  - Perineural invasion in early-stage cervical carcinoma.
AB  - PURPOSE: Evaluation of the association between perineural invasion (PNI) and
      predictive and prognostic factors in early-stage cervical carcinoma patients
      treated with surgery. METHODS: Fifteen PNI (+) and 21 PNI (-) early-stage
      cervical carcinoma patients, primarily treated by surgery, were evaluated
      retrospectively. Patients' complete blood counts and biochemistry tests, tumoral
      prognostic parameters, PNI status, postoperative treatment, recurrence and
      survival data were obtained from the records. RESULTS: The percentage of mean
      depth of stromal invasion was significantly higher in the PNI (+) group (p < or =
      0.05). Vaginal (p < or = 0.05) and uterine (p < or = 0.01) invasion of the tumor
      were significantly more prevalent in the PNI (+) group. Lymphovascular space
      invasion, in particular lymphatic invasion (p < or = 0.05), but not vascular
      invasion (p > 0.05) was significantly more prevalent in the PNI (+) group.
      CONCLUSION: PNI is closely related with stromal invasion in percentage, vaginal
      and uterine involvement and lymphatic invasion of the tumor.

PMID- 19761127
TI  - Spleen involvement in women with ovarian cancer.
AB  - The aim of this study was to determine the prognostic factors of spleen
      metastases in ovarian cancer. A retrospective chart review was conducted and ten
      patients with spleen metastases were evaluated. Eight were Stage III, one Stage I
      and one Stage IV. One patient had a spleen metastasis at the time of ovarian
      cancer diagnosis, whereas, the remaining patients 23.4+12 months after ovarian
      cancer diagnosis. Spleen involvement is a late complication that rarely occurs in
      ovarian cancer and confers a poor prognosis. The interval time between ovarian
      cancer diagnosis and appereance of spleen involvement is the most important
      prognostic factor.

PMID- 19761128
TI  - The use of cod liver oil by patients receiving pegylated liposomal doxorubicin is
      associated with a lack of severe palmar-plantar erythrodysesthesia.
AB  - Pegylated liposomal doxorubicin (PLD) is an effective and tolerable agent in the
      treatment of recurrent and refractory ovarian carcinoma. One of the most common
      dose-limiting toxicities of PLD is palmar-plantar erythrodysesthesia (PPE). We
      report a retrospective review of patients who took cod liver oil (CLO) while
      being treated with PLD at Roswell Park Cancer Institute. None of the patients
      required dose reduction, treatment interruption or discontinuation secondary to
      skin toxicity. No patient experienced grade 2 or greater PPE. The mechanism for
      the development of PLD-induced PPE is unknown. CLO may possibly mitigate it via
      decreased extravasation of PLD and/or by a blunting of the local inflammatory
      response. The effects of CLO should be further evaluated in a prospective,
      randomized trial, and attempts to elucidate the mechanism by which CLO may exert
      its effects should be pursued.

PMID- 19761129
TI  - Clinicopathological features of primary fallopian tube carcinoma: a single
      institution experience.
AB  - PURPOSE OF INVESTIGATION: Primary fallopian tube carcinoma (PFTC) is a rare
      malignancy with only few data existing on the impact of prognostic factors.
      METHODS: We retrospectively analyzed 26 patients. Tissue blocks were reviewed and
      sections were stained for vascular endothelial growth factor (VEGF), matrix
      metalloproteinases 2 and 9 (MMP-2, MMP-9), tissue inhibitors of
      metalloproteinases 1 and 2 (TIMP-1, TIMP-2), c-erbB-2, estrogen (ER), and
      progesterone receptors (PgR). RESULTS: Reactivity for VEGF, ER, PgR, MMP-2, MMP
      9, TIMP-1, TIMP-2 and c-erbB-2 was observed in 85%, 46%, 27%, 11.5%, 58%, 0%, 23%
      and 8% of specimens, respectively. None of the markers studied displayed
      prognostic significance. Regarding clinical prognostic factors, the hazard ratio
      (HR) for progression and death for patients with tumor residuum > 2 cm was 5.24
      (p < 0.01) and 11.19 (p < 0.005), respectively. Patients with advanced stage
      disease had a HR of 12.55 (p < 0.05) for progression, while the HR for death was
      not found to be statistically significant. CONCLUSION: None of the biomarkers
      studied seems to influence survival. Early-stage disease and optimal debulking
      are associated with improved outcome.

PMID- 19761130
TI  - Current management of endometrial hyperplasia and endometrial intraepithelial
      neoplasia (EIN).
AB  - Endometrial hyperplasia is a commonly seen disorder in daily gynecology practice.
      The clinical importance of this pathological entity is the underlying risk of
      carrying a concomittant genital cancer or risk of progression to endometrial
      carcinoma during the follow-up. Despite recent advances in non-invasive
      techniques to define underlying endometrial cancer during the initial diagnosis
      of endometrial hyperplasia, none of these studies are conclusive yet. Today, in
      spite of intense discussions and related studies which aimed to define certain
      prognostic factors (WHO94 vs EIN) to predict cases that would progress to cancer,
      we still do not have a practical and accurate system available to use during
      daily practice. Treatment of endometrial hyperplasias depends on the patient's
      age, fertility desire and the type of hyperplasia. Progestagens are still the
      most commonly used medical treatment modality in these patients. Response rates
      are higher for cases without atypia. In selected cases, hysterectomy may be
      performed as a definitive treatment modality. In this review article, the current
      management of endometrial hyperplasias is summarized in light of the associated
      literature. We also give a brief overview of the EIN classification and its
      clinical importance.

PMID- 19761131
TI  - The contribution of laparoscopy to the diagnosis of adnexal masses in young and
      premenopausal women.
AB  - The purpose of this retrospective study was to investigate the contribution of
      laparoscopy to the diagnosis of adnexal masses in young and premenopausal women,
      in whom surgery was deemed necessary, between the years 2002-2008. A total of 130
      young and premenopausal women scheduled for surgery for an adnexal mass with a
      diameter of 5-10 cm underwent transvaginal ultrasound (US) examination prior to
      surgery. Laparoscopic management was successfully completed for 118 of the 130
      patients in this study; however, 12 required conversion of laparoscopy to
      laparotomy due to endometriosis with extensive bowel adhesions, or suspected
      ovarian malignancy and peritoneal implants. One hundred and twenty-four patients
      (95.38%) had benign lesions, four (3.07%) had borderline tumors and two patients
      had malignant lesions (1.53%). We found a statistically significant association
      between laparoscopic and histological findings. Laparoscopic diagnosis of adnexal
      masses suspicious at US may help avoid many laparotomies for the treatment of
      benign ovarian disorders.

PMID- 19761132
TI  - Accuracy of intraoperative frozen section during laparoscopic management of early
      endometrial cancer.
AB  - OBJECTIVE: The aim of our retrospective study was to correlate the intraoperative
      frozen section (FS) and permanent section (PS) diagnosis among patients with
      early-stage endometrial cancer (FIGO Stage I). METHODS: Retrospective analysis of
      clinical data. A set of 63 women were operated by the technique of laparoscopic
      assisted vaginal hysterectomy with bilateral salpingo-oophorectomy (LAVH with
      BSO). All probands had intraoperative FS biopsy performed with grading and
      myometrial invasion assessment. These data were then compared with PS diagnosis.
      Statistical evaluation was used to detect diagnostic accuracy of FS (sensitivity,
      specificity and positive vs negative predictive value, and accuracy rate).
      RESULTS: The average age was 61 years, BMI 32.4 kg/m2 and operation time
      including lymphadenectomy (LAE) was 108.7 minutes. Sensitivity of FS was 77.8%,
      specificity 98.1%, positive predictive value (PPV) 87.5%, negative predictive
      value (NPV) 96.4% and accuracy rate 95.2%. Suboptimal surgical management due to
      underevaluation of FS biopsy compared to PS diagnosis occurred in 2 patients
      (3.2%). CONCLUSION: Combination of LAVH with BSO and use of intraoperative FS
      enables the surgeon to individualize surgical treatment for every patient to the
      extent of either performing complete operation together with LAE or not.

PMID- 19761133
TI  - Assessment of the predictivity of preoperative serum CA 125 in the differential
      diagnosis of uterine leiomyoma and uterine sarcoma in the Turkish female
      population.
AB  - AIMS: Uterine leiomyomas are the most common benign tumors of the uterus.
      Unfortunately, the diagnostic imaging criteria for distinguishing leiomyosarcomas
      from leiomyomas remain vague. Our aim was to study the preoperative diagnostic
      value of CA 125 in the differential diagnosis of leiomyoma and uterine sarcoma.
      METHODS: The subjects of the study included a total of 2,382 patients aged
      between 20-71 years operated for uterine myoma between the years 2005 and 2008 at
      our hospital, and in the same period 26 patients diagnosed with uterine sarcoma
      who were assessed retrospectively. RESULTS: Assessment of the predictivity of CA
      125 values in the preoperative diagnosis of uterine sarcoma showed it was not
      significant according to the 95% CI related to the area below the curve. The
      assessment of CA 125 values in the uterine sarcoma group showed that those with
      carcinosarcoma had higher CA 125 mean values than other sarcoma groups. The
      relation between staging and CA 125 in all sarcomas could not be statistically
      assessed. CONCLUSION: We concluded that in the differential diagnosis of myoma
      and uterine sarcoma, the preoperative serum CA 125 level did not have any
      predictivity. Additionally, there was no association between staging and CA 125
      in uterine sarcomas.

PMID- 19761134
TI  - Uterine cervical neoplasia prevention in Parque Indigena do Xingu.
AB  - Results of preventive health measures, diagnosis and treatment applied to Parque
      Indigena do Xingu native women were studied. Thirty-seven cases of uterine
      cervical intraepithelial lesions and invasive neoplasias were treated in the
      local villages without referral to an advanced medical center. LEEPs were carried
      out in 32 women, three cold knife conizations, one vaginal hysterectomy and one
      Wertheim Meigs procedure. Results of 53.1% of LEEP surgical procedures did not
      have margin involvement by the lesions. Bleeding complications were seen in
      15.6%. Regular follow-up with two or three cytologic and colposcopic tests in 32
      women was carried out. All cases were negative for lesions. Five women were not
      followed-up due mainly to logistical reasons. Health endeavors adopted in the
      period 2005-2007 brought about a significant reduction of precursor lesions in
      this native aboriginal population without screening resources.

PMID- 19761135
TI  - The role of immunonutrition in gynecologic oncologic surgery.
AB  - BACKGROUND: This study assesses the effect of immunonutrition on biochemical and
      hematological parameters, incidence of infection, postoperative complications,
      mortality rate and length of hospital stay. MATERIAL AND METHODS: A total of 50
      patients operated on for gynecological malignancies were randomly assigned to two
      groups, each receiving two days preoperative and seven days postoperative enteral
      nutrition after intestinal movements started. The patients in group 1 were given
      1000 kcal/d immun-enhancing enteral nutrition (IEN). The patients in group 2
      received 1000 kcal/d standard enteral nutrition. The nutritional (albumin,
      prealbumin), immunologic (CRP, white blood cell (WBC) count, lymphocyte
      population) parameters, length of hospital stay (LOS) and clinical outcomes were
      examined. RESULTS: The two groups did not differ in terms of demographic data,
      nutritional status, surgical status, mortality rate (p > 0.05). WBC count,
      lymphocyte population, CRP levels were significantly higher in group 1 compared
      with group 2 in the postoperative period (p < 0.05). Pulmonary and urinary tract
      infection rates were similar in both groups (p > 0.05) but wound infection, and
      LOS rate were significantly lower in group 1 than group 2 (p < 0.05). CONCLUSION:
      Perioperative immunonutrition proved to be safe and useful in increasing the
      immunologic response. It may decrease postoperative complications and LOS in
      patients undergoing surgery for gynecological malignancy.

PMID- 19761136
TI  - Analysis of the results and long-term follow-up of second-look laparotomy in
      advanced ovarian cancer.
AB  - OBJECTIVE: The goal of the study was to analyze results of 171 second-look
      laparotomy and compare survival of patients with advanced ovarian cancer
      depending on SLL results. RESULTS: We obtained the following results: complete
      pathologic response (CPR)--56.2% (96 patients), microscopic disease (R(micro))-
      12.8% (22 patients), macroscopic disease (R(marco))--31% (53 patients). In
      patients with negative SLL results disease recurrence was diagnosed in 38.5%. We
      compared survival in separate groups of patients depending on SLL results: no
      difference between the CPR group and R(micro) group. Significantly longer
      survival of patients in the R(micro) group was found compared to patients with
      recurrence after negative SLL. There were no differences between the group with
      recurrence after negative SLL and the R(macro) group. CONCLUSIONS: An important
      observation is that the survival rate in patients with recurrence after negative
      SLL was significantly lower compared to patients with microscopic disease. The
      probable explanation for favorable prognosis in the group with microscopic
      disease was early administration of chemotherapy after SLL.

PMID- 19761137
TI  - Peritoneal tuberculosis mimicking peritoneal carcinomatosis.
AB  - PURPOSE: The data of 11 peritoneal tuberculosis (TB) patients is discussed in an
      attempt to better understand this disease. METHODS: Nine patients with clinical
      features mimicking ovarian cancer and two with infertility were evaluated
      retrospectively. RESULTS: The mean age was 40.8 +/- 18.3 years. None had any
      past/family history of TB. Abdominal swelling and pain, appetite loss,
      nausea/vomiting, and primary infertility were the most common complaints. Chest X
      ray suggested TB in one cachexic patient. Six patients had ovarian/primary
      peritoneal cancer on laparotomy. Laparoscopy was performed to determine
      therapeutic modality in one patient and for primary infertility in one patient.
      Three patients were not operated because of suspected TB in one and neoadjuvant
      chemotherapy in two with poor performance scores. They underwent peritoneal or
      omental biopsies; histopathology revealed caseous granulomatous TB lesions.
      Mycobacterium tuberculosis was identified in only two ascitic fluid cultures.
      CONCLUSION: Peritoneal TB should be suspected in endemic areas, especially in
      young patients considered to have peritoneal carcinomatosis.

PMID- 19761138
TI  - Estrogen receptor alpha (ER-alpha) gene polymorphism in patients from the Lodz
      region of Poland with sporadic endometrial cancer.
AB  - OBJECTIVE: Estrogens play a crucial role in the pathogenesis and progression of
      endometrial cancer. The gene ER-alpha is polymorphic and gene variability could
      contribute to the level of protein biosynthesis. METHODS: The aim of this study
      was to evaluate PvuII and XbaI polymorphism of the ER-alpha gene in 120
      postmenopausal women with endometrial cancer in DNA samples obtained from cancer
      tissue. The polymorphisms were determined by PCR-RFLP methods. RESULTS: The
      distribution of the genotypes of PvuII and XbaI polymorphism of ER-alpha in both
      controls and patients did not differ significantly from those predicted by the
      Hardy-Weinberg distribution. There were no significant differences in genotype
      distributions and allele frequencies between subgroups assigned to histological
      stage. CONCLUSIONS: The results suggest that the PvuII polymorphism of ER-alpha
      gene as well as XbaI polymorphism may not be linked with appearance and
      development of endometrial cancer.

PMID- 19761139
TI  - Valid generic substitution of carboplatin for patients with gynecological cancer.

PMID- 19761140
TI  - Synchronous endometrioid carcinoma of the uterine corpus and ovary. A case report
      and review of the literature.
AB  - Synchronous endometrioid carcinoma of the uterine corpus and ovary is an uncommon
      but well recognized event. Diagnosis as either a separate independent primary or
      as a metastatic tumor requires careful consideration of a number of gross and
      histological features. These features illustrate the criteria helpful in
      distinguishing independent primaries from metastatic carcinomas which have a
      different therapeutic implication. The possible link between fertility drugs and
      carcinogenesis still remains controversial. We report a case of a 52-year-old
      woman who came to our hospital with a cystic left ovarian mass (8 cm).
      Hysterectomy and bilateral salpingo-oophorecromy were carried out. Histological
      examinations showed well differentiated endometrioid ovarian cancer and well
      differentiated endometrioid endometrial cancer. The endometrial tumor was
      intramucosal without myometrial or vascular invasion and was associated with
      atypical complex hyperplasia. The woman had not been previously treated with
      ovulation induction drugs. She was free of recurrence two years after surgery.
      Patients with synchronous endometrioid tumors of the endometrium and ovary are
      generally younger than reported for either endometrial adenocarcinomas or ovarian
      adenocarcinomas. They tend to be low grade and early stage and are frequently
      associated with endometriosis. The prognosis of endometrioid type carcinomas is
      better than other histological types of carcinoma.

PMID- 19761141
TI  - Primary ovarian leiomyosarcoma associated with Brenner tumor.
AB  - BACKGROUND: Primary ovarian leiomyosarcoma (POL) is rare. To the best of our
      knowledge, POL associated with a Brenner tumor has not been previously
      documented. CASE: A case of POL associated with a Brenner tumor is reported.
      Although the poorly differentiated component of the tumor was negative for SMA,
      the presence of spindle cells in the higher differentiated component with
      fascicle arrangement and immunoreactivity for SMA and strong staining of a poorly
      differentiated component for desmin and vimentin established the diagnosis.
      CONCLUSION: This case indicates that since malignant tumor cells may lose some
      antigen markers, thorough sampling and immunohistochemistry are necessary. EMA
      immunopositivity only could not preclude the diagnosis of leiomyosarcoma.

PMID- 19761142
TI  - Paratubal endometrioid cystadenocarcinoma: case report and review.
AB  - BACKGROUND: Paratubal masses are common, but paratubal carcinoma is an extremely
      rare entity. CASE: We report a case of a 44-year-old nulliparous female who
      suffered from abdominal pain for three months. Abdominal and pelvic ultrasound
      revealed a 30 cm left adnexal mass originally. Laparotomy with bilateral salpingo
      oophorectomy was performed. Final pathology indicated a heterogeneous tumor with
      benign, borderline, and endometrioid carcinoma areas. A repeat surgery was
      decided in order to complete hysterectomy, omentectomy, pelvic and paraaortic
      lymphadenectomy. Surgical staging did not reveal residual disease at pathological
      examination. After 36 months of follow-up, no recurrence has occurred.
      CONCLUSION: To our knowledge, no case of paratubal invasive endometrioid
      adenocarcinoma has previously been described. This case has been managed
      according to the recommendations of ovarian cancer, which seems to be an
      acceptable option.

PMID- 19761143
TI  - Large retroperitoneal schwannoma mimicking ovarian carcinoma: case report and
      literature review.
AB  - In this article we present a case of retroperitoneal schwannoma localized in the
      pelvic cavity with complete cystic degeneration, mimicking ovarian carcinoma.
      CASE: A 25-year-old nulligravid woman was admitted to our gynecology out-patient
      clinic with the complaint of abdominal distension, right flank pain and
      pollakiuria. Sonographic study showed a cytic mass containing necrotic areas and
      filling the whole pelvic cavity. Computed tomography and colonography suggested
      the possible diagnosis of a right ovarian malign tumor. Laparotomy revealed a
      retroperitoneal cystic lesion. Microscopic examination of the pelvic mass
      confirmed the diagnosis of cystic degenerative schwannoma. After six months of
      initial surgery she is still alive without any evidence of disease. CONCLUSION:
      In the present case, it is emphasized that it is easy to make an error and
      misdiagnose a pelvic mass as an ovarian tumor when it is in fact a tumor from
      another origin. Additonally, clinicians should keep in mind that retroperitoneal
      schwannoma may mimic cystic ovarian carcinoma even in young women.

PMID- 19761144
TI  - Prolonged clinical benefit from platinum-based chemotherapy in a patient with
      metastatic triple negative breast cancer.
AB  - Triple negative breast cancer is a recently defined subgroup of tumors which do
      not express receptors for estrogen or progesterone and which do not show any
      overexpression of HER2 receptors. Tumors with these histopathologic features have
      an unfavorable prognosis and at present there is no standard chemotherapy regimen
      available. However, experimental studies and very recently some clinical data
      showed a benefit from platinum-based chemotherapy. We treated a 52-year-old
      caucasian female with metastatic triple negative breast cancer. She suffered from
      extensive liver disease resistant to taxane treatment and yttrium radiotherapy.
      Cisplatin/ifosfamide (12 cycles) induced regression of the liver metastasis from
      over 30 cm to 6 cm as revealed by CT scan. Dose-limiting toxicity was impairment
      of renal function and pancytopenia. The patient has now been stable for over ten
      months on a metronomic regimen of oral cyclophosphamide. This case report adds to
      recent evidence suggesting good clinical benefits of platinum-based regimens in
      early and advanced triple negative breast cancers.

PMID- 19761145
TI  - Broad ligament leiomyosarcoma in a premenopausal nulliparous woman: case report
      and review of the literature.
AB  - Leiomyosarcomas of the broad ligament of the uterus are extremely rare tumors.
      Most of the time they are diagnosed in older women and despite radical surgical
      treatment prognosis is dismal. We present a rare case of a 38-year-old
      nulligravida presenting with a large, firm mass, fixed in the pelvis. After
      enucleation of the tumor, histological examination revealed the presence of a
      broad ligament leiomyosarcoma, leading to total abdominal hysterectomy and
      bilateral salpingo-ophorectomy three weeks later. Management options and cases
      reported in the literature are reviewed.

PMID- 19761146
TI  - Umbilical metastasis of serous component as a first sign of mixed type epithelial
      ovarian cancer.
AB  - Umbilical metastasis (Sister Mary Joseph's nodule) of malignant neoplasms is a
      rare condition. These nodules usually arise from the gastrointestinal or
      genitourinary tract and may present the first sign of a previously unknown
      primary tumor. We describe a 49-year-old woman presenting with Sister Mary
      Joseph's nodule as the first sign of an extremely aggressive Stage IV mixed type
      epithelial ovarian carcinoma, who died 15 months after the initial diagnosis.
      This is the first case of a Sister Mary Joseph's nodule from a serous component
      of a Stage IV mixed type epithelial ovarian cancer.

PMID- 19761147
TI  - Paget's disease of the vulva in a patient with scleroderma and underlying
      adenocarcinoma: case report.
AB  - Systemic sclerosis (SSc) is a multisystem connective tissue disease characterized
      by fibrosis of the skin and internal organs. Several studies have demonstrated an
      increased frequency of cancer in patients with SSc. We report a case of a 71-year
      old woman with SSc, who presented with an eczematous lesion of the vulva. The
      diagnosis of Paget's disease of the vulva (PVD) was established. The patient
      underwent radical vulvectomy, but 18 months later died due to adenocarcinoma of
      unknown primary origin. SSc and PVD are associated with various types of
      malignancies and patients suffering from these diseases should be under
      surveillance in order for any suspicious symptoms of malignancy to be early
      detected and investigated.

PMID- 19761148
TI  - Vulvar neoplasm and reconstruction of a lesion with a vertical rectus abdominis
      myocutaneous flap: case report.
AB  - A 41-year-old nulliparous woman was admitted to the Institute of Gynecology and
      Obstetrics in 2007 with a painless tumor mass invading the whole vulvoperineal
      and gluteal region. Pathohistological biopsy revealed FIGO Stage II
      squamocellular invasive carcinoma, but clinically it was Stage IVa verucal vulvar
      carcinoma because of malignant infiltration to the distal part of the vagina and
      bilateral gluteal region. The patient underwent radical vulvectomy with bilateral
      inguinofemoral lymphadenectomy and partial vaginectomy. Reconstruction was
      performed after three weeks using a distally based vertical rectus abdominis
      myocutaneous flap (VRAM). A new entrance of the vagina was created. The patient
      was further treated with radiation therapy.

PMID- 19761149
TI  - Gene therapy: how close to clinical reality?

PMID- 19761150
TI  - Lessons from the challenges of polio eradication in India.

PMID- 19761151
TI  - Effect of puerarin on the expression of extracellular matrix in rats with
      streptozotocin-induced diabetic nephropathy.
AB  - BACKGROUND: Inhibition of the formation of advanced glycation end-products delays
      the development of diabetic nephropathy. Puerarin decreases the formation of
      these products. We studied the effect of puerarin in a rat model of diabetic
      nephropathy. METHODS: Three groups of rats were studied: a control group, a
      diabetic group in whom diabetic nephropathy was induced by intraperitoneal
      injection of streptozotocin, and a puerarin group in which diabetic rats were
      treated with puerarin. During and after treatment, measurements were made on the
      rats' general status, blood glucose level, blood urea nitrogen, serum creatinine,
      creatinine clearance rate and urinary albumin excretion over 24 hours. The
      expression of collagen I and heparan sulphate proteoglycan in the extracellular
      matrix of the glomerulus was assessed by immunohistochemistry. RESULTS: Rats in
      the puerarin group had a better general condition than those with diabetes. They
      also had lower blood urea nitrogen, serum creatinine and urinary albumin
      excretion rate over 24 hours compared with those in the diabetic group. The
      creatinine clearance and expression of heparan sulphate proteoglycan in the
      kidney also increased significantly in the puerarin group compared with that in
      the diabetic group. CONCLUSION: Puerarin seems to have certain protective effects
      on diabetic nephropathy induced by streptozotocin. This is caused possibly by
      regulating the expression of glomerular extracellular matrix.

PMID- 19761152
TI  - Intensified pulse polio immunization: time spent and cost incurred at a primary
      healthcare centre.
AB  - BACKGROUND: Despite launching the polio eradication initiative in 1995, India is
      among the world's largest reservoir of wild poliovirus with 559 cases of
      poliomyelitis reported in 2008. This continued failure has been criticised for
      its negative impact on routine healthcare delivery. We assessed the impact of the
      pulse polio immunization programme at the primary health level in terms of
      services, time and cost. METHODS: All activities during a single round of
      intensified pulse polio immunization were modelled on actual requirements at the
      primary health centre at Dayalpur in Haryana. Total person-hours and cost per
      child vaccinated at the primary health centre were computed. RESULTS: Almost all
      routine healthcare services at the primary health centre were suspended during
      the round. Total person-hours consumed were 4446 and the total direct cost was Rs
      24.2 per child vaccinated during a single round of the intensified pulse polio
      immunization programme. CONCLUSION: A single round of intensified pulse polio
      immunization consumes a substantial number of person-hours and leads to a
      temporary suspension of routine services provided at the primary health centre.
      This should be factored in while planning any future strategy of polio
      eradication or control and suggests the need to re-think the 'intensified pulse
      polio strategy'.

PMID- 19761153
TI  - Clinical profile and outcome of diabetic ketoacidosis in children.
AB  - BACKGROUND. There is little information on the clinical profile and outcome of
      children with diabetic ketoacidosis in India. We analysed the data of children
      managed by us at a tertiary care hospital. METHODS. We retrospectively analysed
      the case records of 21 children (13 boys and 8 girls) with diabetic ketoacidosis
      admitted to our hospital from January 2004 to August 2008. They were managed
      using a standard protocol including intravenous fluids and insulin infusion.
      Blood glucose, serum electrolytes, blood urea, arterial blood gases and urinary
      ketones were monitored at regular intervals. The outcomes were assessed. RESULTS:
      The median age at presentation was 8 years and 17 children (80%) were detected to
      have diabetes mellitus at the time of presentation. Twelve children (57%)
      presented with severe diabetic ketoacidosis. Polyuria with polydipsia was the
      commonest clinical presentation (17). All of them had elevated HbA1C levels. The
      average length of stay in the paediatric intensive care unit was 2.9 days. The
      median time for the arterial blood gases to become normal was 19 hours and for
      urinary ketones to become non-detectable was 28 hours. None of the children
      received bicarbonate and there were no complications or mortality. All the
      children were doing well on follow up at 3 months. CONCLUSION; The outcome of
      active management of diabetic ketoacidosis in children is rewarding. The use of a
      standard protocol for management was associated with no complications or
      mortality in our series.

PMID- 19761154
TI  - Fabry disease: a treatable lysosomal storage disorder.
AB  - Fabry disease is a lysosomal storage disease with an X-linked inheritance
      pattern, which presents in childhood as acroparaesthesias. Its non-specific
      symptoms often lead to delays in the diagnosis. We report the case of a 13-year
      old boy who presented with typical acroparaesthesia of Fabry disease, his younger
      brother had gastrointestinal manifestations of the disease and their mother's
      symptoms suggested that she is a carrier. Enzyme replacement therapy helped in
      ameliorating the patient's symptoms and preventing complications such as renal
      failure, stroke and cardiovascular disorders.

PMID- 19761155
TI  - Simple measures to reduce perioperative morbidity and mortality.

PMID- 19761156
TI  - An integrated nutrition and health programme: the impact on neonatal mortality in
      rural northern India.

PMID- 19761157
TI  - Further progress in the treatment of multiple myeloma?

PMID- 19761158
TI  - Faculty development and medical education units in India: a survey.
AB  - BACKGROUND: Faculty development in medical education is gaining momentum in
      India. While planning a National Conference on Medical Education (NCME 2007), we
      did a survey of principals and faculty of medical colleges to understand the
      status of faculty development programmes and medical education units in medical
      colleges in India. METHODS: Questionnaires were sent to principals of medical
      colleges by surface mail and to faculty through a web-based programme to elicit
      information on various aspects of faculty development programmes and medical
      education units. The responses of both groups were analysed. RESULTS: The number
      of medical education units has increased rapidly after regulations have been
      revised in 1997 by the Medical Council of India. The main activities of medical
      education units were to conduct workshops targeted at medical teachers. The
      frequently covered topics were teaching-learning, media and student assessment.
      Lectures dominated the methodology of imparting information. Evaluation was done
      mainly by feedback questionnaires and pre-test/post-test questionnaires. Projects
      and follow up were rarely used. The responses from both groups were strikingly
      similar. The major strengths of medical education units were perceived as
      availability of trained and motivated faculty, good infrastructure and supportive
      leadership. The shortcomings were lack of infrastructure, funding and full-time
      faculty, besides time constraints and resistance to change. The respondents
      suggested strengthening of infrastructure, appointment of full-time faculty and
      staff, incentives and recognition of contributions to faculty development, making
      participation a mandatory requirement, extending the scope of faculty development
      programmes to include research and networking at the national level. Conclusion.
      The study reveals the need for policy decisions that support functioning of
      medical education units in India besides active participation of the faculty.

PMID- 19761159
TI  - The Commission on Social Determinants of Health: mainstreaming social
      inequalities in public health education in India.

PMID- 19761160
TI  - Health, health workers and human rights: Dr Binayak Sen and the silence of the
      medical fraternity in India.

PMID- 19761162
TI  - The heat targets.

PMID- 19761161
TI  - Glycaemic control and macrovascular disease in people with diabetes mellitus.

PMID- 19761163
TI  - Career paths for a young doctor: stepping outside the clinic.

PMID- 19761164
TI  - Aspirin for diabetes: are we adhering to ADA guidelines?

PMID- 19761165
TI  - The outsourcing industry and health implications: time for a research agenda?

PMID- 19761166
TI  - Tuberculosis is the exception to Occam's razor.

PMID- 19761167
TI  - Deep vein thrombosis: risk factors and prevention in surgical patients.
AB  - BACKGROUND: Deep vein thrombosis (DVT) is a cause of preventable morbidity and
      mortality in hospitalized surgical patients. The occurrence of the disease is
      related to presence of risk factors, which are related primarily to trauma,
      venous stasis and hyper-coagulability. DVT seems not to be taken seriously by
      many surgeons in Nigeria. This is despite comprehensive studies that show no real
      differences in racial demography of the disease. OBJECTIVE: To highlight the
      importance of physician awareness about DVT especially its risks and prevention
      methods. METHODS: A detailed literature search was completed to extrapolate
      articles that described DVT risks and prevention. This involved hand and online
      searches. Specific search terms used included DVT/risk factors/prevention. The
      searches generated 468 papers. Of these 57 papers were included in the review.
      RESULTS: Predominant risk factors for DVT include middle or old age, prolonged
      surgery, trauma, confinement, presence of malignancy and insertion of deep venous
      catheters. In women, contraceptive use, hormone replacement therapy, pregnancy
      and the puepernum are a additional risk factors. Prophylactic measures include
      those directed at eliminating venous stasis and those directed at changes in
      blood coagulability. CONCLUSION: Deep Venous Thrombosis is a common disease with
      fatal and serious long term burdensome complications. We must target primary and
      secondary prophylaxis to improve survival and reduce morbidity from this
      preventable disease.

PMID- 19761168
TI  - The import of abdominal pain in adults with sickle cell disorder.
AB  - BACKGROUND: The aetiology, clinical correlates and outcome of abdominal pain in
      Nigerian adults with sickle cell disorder (SCD) have not been extensively
      reported. OBJECTIVE: To determine the prevalence of abdominal vasoocclusive
      crisis in sickle cell patients with abdominal pain and their clinical correlates
      if any. METHODS: Clinical records of adults with SCD (Hb SS and Hb SC) attending
      the Haematology Outpatients' Clinic of the Obafemi Awolowo University Teaching
      Hospitals Complex, Southwest Nigerian, over a ten-year period, were reviewed.
      Demographic, clinical and laboratory data with respect to abdominal pain were
      retrieved. Data were analysed using appropriate descriptive and inferential
      statistics. RESULTS: A total of 154 records (128 Hb SS and 26 Hb SC) were
      available for assessment. The patients mean ages were 22.5 +/- 7.3 years (Hb SS
      patients) and 24.2 +/- 9.7 years (Hb SC patients) (p > 0.05). The prevalence of
      abdominal pain was 39.1% and 30.8% in Hb SS and Hb SC respectively (p > 0.05).
      Pain was commonly in the epigastrium; dull in 35% Hb SS, but peppery/burning in
      37.5% Hb SC. All patients with abdominal vaso-occlusive crisis (VOC) had
      diffuse/generalised dull abdominal pains. A diagnosis of gastritis/peptic ulcer
      disease was made in 50% of Hb SC patients and 28% of Hb SS patients. Abdominal
      VOC was diagnosed in 26% Hb SS, but none in Hb SC patients. The size of the liver
      or spleen and the haematocrit of Hb SS patients did not correlate with the
      frequency of abdominal pain generally or abdominal VOC specifically. CONCLUSION:
      The prevalence rates and patterns of abdominal pain in Hb SS and Hb SC patients
      appear similar. Abdominal VOC characterised by diffuse/generalised dull abdominal
      pain occurred in only Hb SS patients and may be a marker of disease severity in
      these patients.

PMID- 19761169
TI  - Plasma lipid peroxidation and totalantioxidant status among dyslipidaemic and
      hypertensive Nigerians with high risk of coronary heart disease.
AB  - BACKGROUND: The oxidative modification hypothesis of atherosclerosis predicts
      that low density lipoprotein-cholesterol (LDL-C) oxidation is an early event in
      atherosclerosis and that oxidized LDL-C contributes to atherogenesis OBJECTIVE:
      To determine a link, if any, between the plasma lipid peroxidation and total
      antioxidant status (TAS) among dyslipidemic and hypertensive Nigerian patients
      with high risk of coronary heart disease. METHODS: The study groups comprised 58
      hypertensive adult Nigerians whose fasting plasma total cholesterol (TC) levels
      were > 5.5 mmol/L and with high risk coronary heart disease (CHD) lipid fraction
      i.e. 'the ratio of high density lipoprotein cholesterol to total cholesterol'
      (HDL-C/TC) < 0.13 were selected for the study. The control groups comprised 58
      non hypertensive adult Nigerians with (HDL-C/TC) > 0.30. RESULTS: The mean +/- SD
      TAS level (1.02 +/- 0.15 mmol/L trolox) for males and (0.99 +/- 0.17 mmol/L) for
      females were significantly reduced (p < 0.05) compared to the controls; however
      (MDA) level (5.15 +/- 0.82 mmol/ml) for males and (5.06 +/- 0.73 mmol/ml) for
      females were significantly increased (p < 0.01) compared to the controls. The
      mean +/- SD plasma TC and LDL-C malonyl level (5.87 +/- 0.23 mmol/L and 4.65 +/-
      0.34 mmol/L) were significantly increased (p < 0.01) in males hypertensive
      compared to the control. An inverse correlation between the TAS/TC(r = -0.53, p <
      0.001) and TAS/LDL-C (r = -0.50, p < 0.001), however a direct correlation between
      the MDA/TC(r = 0.51, p < 0.001) and MDA/LDL-C (r = 0.48, p < 0.01) for males
      hypertensive were found. In female subjects the mean +/- SD plasma TC (5.95 +/-
      0.13 mmol/L) and LDL-C (4.45 +/- 1.04 mmol/L) were significantly increased (p <
      0.05) and (p < 0.01) respectively compared to the controls. Also in hypertensive
      females inverse correlation between the TAS/TC (r = -0.59, p < 0.001) and TAS/LDL
      C (r = -.41, p < 0.01), and a direct correlation between the MDA/TC ( r= .48, p <
      0.01) and MDA/LDL-C (r = 0.31, p < 0.05) were found. CONCLUSION: Since
      dyslipidaemia, hypertension and lipid peroxidation were directly relate to the
      severity of atherosclerosis, elimination of free radicals in the plasma before
      the peripheral tissues can take them up might reduce atherosclerosis. In view of
      our present findings, a management strategy aimed at simultaneously reducing
      lipid peroxidation and increasing total antioxidant status in dyslipidemic
      patients may be of benefit.

PMID- 19761170
TI  - Menstrual characteristics of secondary school girls in Ibadan, Nigeria.
AB  - BACKGROUND: Disturbances of menstrual function are the commonest complaints among
      adolescents. Disorders of menstruation may have implications for future
      reproductive health. OBJECTIVE: To assess menstrual patterns among school girls
      in Ibadan, south-western Nigeria. METHODS: This was cross-sectional descriptive
      study in which 1,213 apparently healthy school girls were selected by multistage
      sampling technique in fifteen secondary schools from the five local governments
      within the metropolis. Information about details of menstrual experience was
      obtained with a self-administered questionnaire. RESULTS: The girls were aged
      between 9 and 23 years. Majority of respondents 768 (633%) experienced normal
      cycle length, 391 (32.2%) had short cycles; and 55 (4.5%) had cycle length
      greater than 35 days. Prevalence of normal cycles increased with increasing age;
      abnormalities of cycle length tended to decrease with increasing age (p < 0.01).
      The majority, 1,152 (95%), had normal menstrual loss. The majority 882 (72.7%)
      experienced dysmenorrhoea; severe dysmenorrhoea was reported by 154 (12.7%).
      Cycle length was not associated with presence of dysmenorrhoea (p > 0.05); 695
      (57.3%) had symptoms of pre-menstrual syndrome. CONCLUSION: Prevalence of
      menstrual abnormalities among adolescent schoolgirls is high. More attention
      should be paid to identify and treat these menstrual morbidities.

PMID- 19761171
TI  - Ultrasonographic ocular diameters in Nigerians.
AB  - BACKGROUND: There is little information on the biometric ultrasonography of the
      eyeball, especially in Africans. The eyeball diameters form the basis for the
      calculation of the intraocular lens power and diagnosis of axial hypermetropia
      and myopia OBJECTIVE: To determine the ocular diameters of healthy Nigerian eyes.
      METHODS: Measurements of the eyeball in volunteers were taken on the B-mode image
      using a Medison's Sonoace 1500 ultrasound machine using a 6.5 MHz curvi-linear
      transducer placed over the closed eyelid. The vertical, horizontal and axial
      diameters of the eyes of healthy subjects were recorded. The age and sex of the
      subjects were also recorded. RESULTS: Four hundred eyes of 200 subjects
      comprising 125 females (62%) and 75 (38%) males (38%) were studied. The age range
      was 3-92 years with an overall mean age of 41.48 +/- 23.26 years for both sexes.
      The mean axial eyeball diameter for the entire study population was 21.7 +/- 0.16
      mm. There was a gradual increase in all eyeball diameters with age. The highest
      value for eyeball diameter (22.5 +/- 0.18 mm) was recorded for the elderly age
      group. The (SD) mean eyeball diameters for males were slightly higher than that
      for the females; mean for males, 21.8 +/- 0.13 mm, 95% CI = 21.781-21.819, vs
      females, 21.6 +/- 0.14 mm, 95% CI = 21.581-21.619. However, the difference was
      not statistically significant (p = 0.409). CONCLUSIONS: The eyeball diameters
      found in this sample of Nigerians are lower than the dimensions reported in
      Caucasians. These values may be used as reference values for normal African eyes.

PMID- 19761172
TI  - Visual outcome of cataract surgery in University College Hospital, Ibadan
      Nigeria.
AB  - BACKGROUND: Cataract is a leading cause of avoidable blindness, while cataract
      surgery is the commonest major surgical procedure worldwide. OBJECTIVE: To
      evaluate the visual outcome and causes of poor vision in patients who had
      cataract extraction at a major hospital in Nigeria. METHODS: A retrospective
      study of the case notes of patients who had cataract extraction in the Eye Clinic
      of University College Hospital, Ibadan between July and Dec. 2004 was done. The
      visual outcome was analyzed using the WHO categorization of visual outcome and
      those with poor visual outcome evaluated for the cause of such poor outcome.
      RESULTS: Forty-seven (40.2%) of the eyes had good outcome before refraction and
      the number increased to 80 (67.8%) after correcting for postoperative refractive
      error. The highest single cause of poor visual outcome was uncorrected refractive
      error, 32 (47%) eyes. Other causes included posterior capsule opacification 7
      (18.4%) eyes, preexisting ocular co-morbidity such as glaucoma, optic atrophy and
      maculopathy 6 (15.9%) eyes. CONCLUSIONS: This review showed that uncorrected
      refractive error and posterior capsular opacification were the major causes of
      poor visual outcome after cataract surgery. Preoperative biometry for all
      patients, meticulous intra operative cortical clean up, adoption of the cataract
      surgery outcome tally sheet and better patient selection will help improve the
      outcome of our cataract surgeries.

PMID- 19761173
TI  - Trends in emergency surgical admissions in a tertiary health centre in Nigeria.
AB  - BACKGROUND: In the past, elective surgery was the predominant in-patient workload
      of consultant surgeons. Recently, emergency cases are forming an increasing part
      of the in-patient workload. OBJECTIVE: The aim of this study was to appraise the
      rising incidence of emergency surgical admissions (EMA) as well as the factors
      associated with the change. METHODS: A retrospective review of surgical
      admissions in the Department of Surgery Ahmadu Bello University Teaching Hospital
      Zaria, Nigeria. Every third year from 1970 to 2000 was selected giving a total of
      10 years for review. Details of all surgical admissions were analysed including
      age and sex of the patients, incidence of the most common primary diagnoses,
      proportion of patients having operation during their emergency admission,
      duration of hospital stay and mortality. RESULTS: Overall, 19,436 emergency and
      19,528 elective surgical admissions (ELA) were made. The ratio of EMA to ELA per
      100,000 catchment's area population rose from 1:1.6 in 1973 to 1.4:1 in 2000.
      Between 1995 and 2000, the rise in EMA was 8.0% per year compared to 1.5% rise in
      ELA. About 30% of ELA were cancelled due to factors related to EMA. Rising
      incidence of appendicitis, acute infections and trauma accounted for most of the
      increase in EMA. Operations during EMA increased from 35.3% in 1973 to 45.0% in
      2000. Postoperative mortality remained at about 6.0% CONCLUSION: Emergency
      surgical admissions have increased and now exceed elective admissions. This has
      placed considerable strain on our limited resources and our ability to cope with
      increasing demand of elective surgery.

PMID- 19761174
TI  - Menstrual characteristics amongst south-eastern Nigerian adolescent school girls.
AB  - BACKGROUND: Information on pattern of menstruation and its implications is
      lacking amongst adolescents in Nigeria. OBJECTIVE: To examine the characteristics
      of menstruation amongst adolescent Igbo school girls with respect to the
      biosocial characteristics, the pattern of menstruation, associated complications,
      and the source of information on menstruation. METHODS: A descriptive cross
      sectional study of 550 students recruited from a multi-sampling of 50 secondary
      schools in Onitsha, Anambra State, Nigeria, using pre-tested, semistructured, and
      interviewer administered questionnaires. RESULTS: Four hundred and sixteen
      (75.6%) respondents were aged 15-17 years; 338 (61.4%) of whom were Catholics.
      Menarcheal age range of respondents was 11-16 years, with a mean age of 13.40 +/-
      1.15 years. Menstruation was regular in 410 (74.5%), and irregular in 124 (22.5%)
      of respondents. Duration of menstrual flow ranged between two and eight days,
      although a four-day flow occurred most commonly, 268 (53.6%). Abdominal pain,
      (66.2%), and waist pain, (38.5%), constituted the major problems associated with
      menstruation, followed by depression, (24.4%); vomiting, (6.9%); school
      absenteeism, (4.5%); anorexia, (1.8%); weakness, (1.5%); and increased appetite,
      (1.1%). The commonest source of information on menstruation (prior to menarche)
      amongst respondents was from the mother, 48.4%, followed by elder sister, and
      friends --14.2%, and 8.7% respectively, while the teacher constituted the least
      source, 1.1%. CONCLUSION: The characteristics of menstruation in this study do
      not differ considerably from what obtains amongst other adolescent girls.
      Associated complications may have profound psychosocial impact on the growing
      adolescent girl, requiring address, best achieved through the empowerment of
      mothers and teachers under a comprehensive family life education scheme.

PMID- 19761175
TI  - Profile of breast diseases at a self-referral clinic in Ghana.
AB  - BACKGROUND: Breast cancer is a common malignancy in Ghana, and many patients are
      referred with advanced disease and long duration of symptoms. OBJECTIVE: To
      determine the spectrum of breast disease diagnosed through patient self-referral
      in Ghana. METHODS: A breast clinic, where patients could walk in without
      referral, was started in the Korle Bu Teaching Hospital in 2001. A team of
      surgeons, radiation oncologists, oncology nurses, a clinical psychologist and a
      clinical pharmacist sat in conference once a week to see and discuss self
      referred patients. RESULTS: Seven hundred and forty eight patients, mean age 38.6
      (range 8-85) years, were seen during a four-year period. There were 741 females
      and seven males. The main complaints were pain 450 (50.2%), lump 257 (28.7%) and
      nipple discharge 62 (8.3%). Fifty (5.6%) came for check-up; 139 (18.6%) had more
      than one complaint. The mean (S.D.) duration of symptoms was; for nipple
      discharge 14.1 (10.5) months, lump 11.9 (7.7) months, and pain 11.3 (8.9) months.
      The main diagnoses were: Normal breasts 192 (27.7%), mastalgia 135 (18.1%),
      fibroadenosis 114 (15.2%), fibroadenomas 84 (11.2%), breast cancer 58 (7.8%),
      suspected breast cancer 25 (3.3%), galactorrhea 9 (1.2%), mastitis 8 (1.1%),
      musculoskeletal pain 8 (1.1%), duct ectasia 8 (1.1%), mondor's disease 7 (0.94%)
      and recurrent breast cancer 6 (0.8%). In patients with breast cancer, 42 (66%)
      had advanced disease, 6 (9.4%) had recurrent disease and 4 (63%) had metastatic
      disease. CONCLUSION: The number of self-referrals, detected breast cancers and
      duration of symptoms justify the need for self-referral clinics in Ghana.

PMID- 19761176
TI  - Characteristics of vitiligo in Lagos, Nigeria.
AB  - BACKGROUND: Vitiligo is disfiguring in the darker racial ethnic group as a result
      of the sharp contrast between the normal skin and the depigmented skin.
      OBJECTIVE: To describe the epidemiology and clinical profile of vitiligo patients
      at the dermatology clinic of an urban tertiary hospital of Lagos University
      Teaching Hospital. METHODS: All consecutive patients with a diagnosis of vitiligo
      seen at the Dermatology Clinic between October 2003 and October 2006, were
      included in the study. The diagnosis of vitiligo was made based on the clinical
      findings of depigmented macules or patches with a sharp margin, normal texture,
      intact sensations and no scaling. RESULTS: The diagnosis of vitiligo was made in
      186 (2.8%) patients, with a slight female preponderance. Vitiligo affected all
      age groups: the youngest presented at age one and the oldest at eighty six years
      of age. The face and the limbs were the most affected parts of the body. Fifteen
      (0.81%) patients presented with features suggestive of associated autoimmune
      disease like, Type 1 Diabetes. CONCLUSION: The frequency of vitiligo in this
      study is similar to those obtained in previous studies from different parts of
      Nigeria. The patients will benefit from other modalities of management apart from
      the medical management offered hence a designated centre for management of
      vitiligo will be a respite to them.

PMID- 19761177
TI  - Incidence of acute appendicitis in Kumasi, Ghana.
AB  - BACKGROUND: Acute appendicitis is a leading cause of surgical admissions for
      abdominal pain in many hospitals. OBJECTIVE: To report the incidence of acute
      appendicitis in Kumasi and highlight the increasing admissions rates of the
      disease in the metropolis. METHODS: A combined prospective and retrospective
      analysis of hospital records was performed to obtain data on the age and sex of
      each patient, and the total number of patients who had appendectomies performed
      for acute appendicitis. Data were obtained from the major hospitals in Kumasi
      including Komfo Anokye Teaching Hospital (KATH), the Kwame Nkrumah University of
      Science and Technology Hospital simply known as University Hospital (UH), the
      Seventh Day Adventist Hospital (SDAH), the Animwa Medical Centre, the Kumasi
      South Hospital and the South Suntresu Health Centre for the period January 2000
      to December 2005. RESULTS: There were a total of 1266 patients 869 (68.6%) males
      and 397 (31.4%) females with an overall male to female ratio of 2.2:1.The yearly
      incidence of acute appendicitis in Kumasi was 1.8 per 10,000 of the population.
      The peak incidence was in the 25-29 year age groups in both sexes. Appendicitis
      was twice as common in the male and in all age groups. The admission rates at the
      start of the study were 1.7/10,000 and 0.8/10,000 for male and females
      respectively and 3.4/10,000 and 1.4/10.000 for male and females at the conclusion
      of the study. CONCLUSION: In Kumasi acute appendicitis occurs in all age groups
      of both sexes. Males are more affected than females. Admission rates from the
      disease are rising in both sexes most likely due to increasing hospital
      attendance.

PMID- 19761178
TI  - Genito-urinary reconstruction in southern Nigeria.
AB  - BACKGROUND: Urologic cases constitute about 25% of a busy surgical practice in
      Nigeria with up to 50% of these cases being genito-urinary abnormalities in
      adults and children. As most urologic surgery in Nigeria is done by general
      surgeons, a knowledge of the disease pattern and effective techniques in
      management would be helpful in surgical training. OBJECTIVE: To describe the
      disease pattern and surgical outcomes in patients undergoing genito-urinary
      reconstruction in southern Nigeria METHODS: We retrospectively reviewed the
      medical records of patients who underwent genito-urinary reconstructive
      procedures by two urologists and one paediatric surgeon over a 7-year (1991-1998)
      period at two tertiary referral centres in southern Nigeria. We extracted data
      such as age, sex, nature of pathology, surgical therapy and outcomes. Patients
      with a follow up of 12 months were excluded. The pattern of genito-urinary
      disease, type and outcome of surgical therapy, and complications were determined.
      RESULTS: Two hundred and twenty seven patients (121 men, 39 women, and 67
      children) underwent genito-urinary reconstruction during the seven years spanning
      1991-1998. The study population consisted of 160 adults and 67 children (< 15
      years old). Mean patient age was 43 years with a range of 18-87 years for adults
      and three years (range 18 months-13 years) for children. Mean follow up duration
      was 15 months, (range--13 months-seven years). Urethral abnormalities comprised
      69% (98/ 227) of the lesions. The most common abnormality was urethral stricture
      in 98 (43%) patients. Urethral strictures were reconstructed as follows; primary
      anastomosis 83 (84.6%), pedicled penile skin island 6 (6.1%), Blandy 2 stage, 4
      (4%), meatoplasty three (3%) and meatotomy, two (2%). The overall complication
      rate for repair of urethral strictures was 4.08%. There were 79 (35%) congenital
      lesions, including hypospadias 62 (27%), pelvi-ureteric junction obstruction 13
      (6%), bladder exstrophy 2 (0.8%), chordee without hypospadias, 2 (0.9%), and
      concealed penis 1 (0.4%). These were managed using the following techniques;
      MAGPI, 30 (48.3%), urethroplasty, 22 (10%) single stage 10 (45%), two-stage 12
      (55%), and urethral mobilization 10 (16%). Vesico-vaginal fistula complicating
      obstructed labour and pelvic surgery was the main cause of urinary fistulae. Ten
      patients underwent microsurgical epididymo-vasostomy for obstructive azoospermia
      resulting in three pregnancies. CONCLUSION: Lower urinary tract reconstruction
      represents a major proportion of urologic surgery in southern Nigeria. Management
      by urologic specialists results in good outcomes, therefore urologic training in
      this area should include a large component of lower urinary tract reconstruction.

PMID- 19761179
TI  - Enteropathogenicity of Bacillus cereus isolated from some Nigerian foods.
AB  - BACKGROUND: Bacillus cereus is a soil bacterium and has been isolated from cooked
      and uncooked rice, milk and dairy products, meat, spices, garlic, vegetables,
      cereals and infant formulae. OBJECTIVE: To report on the enteropathogenicity of
      B. cereus isolated from Nigerian foods. METHODS: Forty-five Bacillus cereus
      isolates classified as diarrhoeal and emetic strains were assayed for enterotoxin
      production. Thirty extractions were from diarrhoeal strains and 15 from emetic
      strains. RESULTS: Forty-five Bacillus cereus isolates classified as diarrhoeal
      and emetic strains were assayed for enterotoxin production. Of the 30 toxin
      extractions from B. cereus classified as diarrhoeal strains, 18 (60%) gave
      positive ileal-loop reactions, while 15 toxin extractions from emetic strains of
      B. cereus gave negative ileal-loop reactions. CONCLUSION: The work has
      demonstrated the distribution and toxigenicity of B. cereus in various Nigerian
      foods. An appreciable number of Nigerian food isolates are capable of causing
      diarrhoea. Forty percent of the enterotoxigenic isolate were mild to severe
      enterotixin producers, with 31% mild, 6.7% moderate and 2.2% severe.

PMID- 19761180
TI  - Classical Rett Syndrome in a Ghanaian child: a case report.
AB  - BACKGROUND: Although Rett Syndrome, a neurodevelopmental disorder in females is
      thought to be relatively common from worldwide studies. There are few or probably
      no reports from the West African sub region. OBJECTIVE: To report a case of Rett
      Syndrome in a Ghanaian. METHODS: Using International Diagnostic criteria for Rett
      syndrome, a 21-month old female presenting with mental retardation and autistic
      features was followed up for nearly two years and all clinical features and
      relevant investigations recorded. RESULTS: Pregnancy and delivery were
      uneventful, child developed normally till age 12 years when her development began
      to decline. She exhibited handwriting and bruxism was underweight with
      microcephaly investigations were normal except for epileptiform discharges on EEG
      and prolonged QT interval on ECG. She was treated with melatonin and dompor for
      her sleep and reflect problems respectively. The patient met the criteria for a
      diagnosis of classical Rett Syndrome. CONCLUSION: This report shows that Rett
      syndrome does exist in the West African sub-region. It is possible to identify
      the condition in girls presenting with mental retardation or autistic features if
      they are appropriately followed up.

PMID- 19761181
TI  - Biofunctionalized protein resistant oligo(ethylene glycol)-derived polymer
      brushes as selective immobilization and sensing platforms.
AB  - Poly(oligo(ethylene glycol) methacrylate) (POEGMA) brushes are extremely protein
      resistant polymer coatings that can reduce nonspecific adsorption of proteins
      from complex mixtures such as blood, sera and plasma. These coatings can be
      prepared via atom transfer radical polymerization with excellent control of their
      thickness and grafting density. We studied their direct functionalization with
      streptavidin and developed an assay for determining which coupling conditions
      afford the highest streptavidin loading efficiency. Disuccinimidyl carbonate was
      found to be the most efficient activating agent for covalent capture of the
      receptor. Using infrared and X-ray photoelectron spectroscopy, fluorescence
      microscopy, surface plasmon resonance, and ellipsometry, we examined how
      structural parameters such as the length of the oligo(ethylene glycol) side chain
      affect streptavidin functionalization, but also immobilization of biotinylated
      antibodies, subsequent selective secondary recognition and nonspecific binding of
      proteins. We found evidence that large macromolecules cannot infiltrate dense
      polymer brushes and that bulky antibody recognition occurs in the upper part of
      these coatings.

PMID- 19761183
TI  - Platinum-catalyzed direct amination of allylic alcohols under mild conditions:
      ligand and microwave effects, substrate scope, and mechanistic study.
AB  - Transition metal-catalyzed amination of allylic compounds via a pi-allylmetal
      intermediate is a powerful and useful method for synthesizing allylamines. Direct
      catalytic substitution of allylic alcohols, which forms water as the sole
      coproduct, has recently attracted attention for its environmental and economical
      advantages. Here, we describe the development of a versatile direct catalytic
      amination of both aryl- and alkyl-substituted allylic alcohols with various
      amines using Pt-Xantphos and Pt-DPEphos catalyst systems, which allows for the
      selective synthesis of various monoallylamines, such as the biologically active
      compounds Naftifine and Flunarizine, in good to high yield without need for an
      activator. The choice of the ligand was crucial toward achieving high catalytic
      activity, and we demonstrated that not only the large bite-angle but also the
      linker oxygen atom of the Xantphos and DPEphos ligands was highly important. In
      addition, microwave heating dramatically affected the catalyst activity and
      considerably decreased the reaction time compared with conventional heating.
      Furthermore, several mechanistic investigations, including (1)H and (31)P{(1)H}
      NMR studies; isolation and characterization of several catalytic intermediates,
      Pt(xantphos)Cl(2), Pt(eta(2)-C(3)H(5)OH)(xantphos), etc; confirmation of the
      structure of [Pt(eta(3)-allyl)(xantphos)]OTf by X-ray crystallographic analysis;
      and crossover experiments, suggested that formation of the pi-allylplatinum
      complex through the elimination of water is an irreversible rate-determining step
      and that the other processes in the catalytic cycle are reversible, even at room
      temperature.

PMID- 19761184
TI  - First principles modeling of eosin-loaded ZnO films: a step toward the
      understanding of dye-sensitized solar cell performances.
AB  - A theoretical investigation of eosin-Y (EY) loaded ZnO thin films, the basic
      components of a dye-sensitized solar cell (DSSC), is presented. The EY/ZnO
      wurtzite (10-10) system has been fully described within a periodic approach using
      density functional theory (DFT) and a hybrid exchange-correlation functional.
      Reduced systems were also analyzed to simulate an electron transfer from the dye
      to the substrate. Injection times from dye to the semiconductor were calculated
      using the Newns-Anderson approach. Finally, the UV-visible spectra of EY/ZnO
      films were simulated using a time-dependent DFT approach and compared to that of
      the EY molecule computed in solution. The results obtained highlight that EY
      strongly adsorbs on the ZnO substrate contributing significantly to the
      electronic structure of the adsorbed system. The UV-visible spectral signature of
      the isolated EY molecule is still found when adsorbed on ZnO but the analysis of
      Gamma-point crystalline orbitals reveals that a direct HOMO-->LUMO excitation
      cannot lead to a direct electron injection into the semiconductor, the first
      unoccupied orbital with contributions from the ZnO substrate being the LUMO + 1.
      As a consequence, a two photon injection mechanism is proposed explaining the low
      efficiency of the EY/ZnO solar cells. On this basis, possible strategies for
      enhancing the cell efficiency are presented and discussed.

PMID- 19761185
TI  - Screen and genetic assessment of tea germplasms with elevated methylated
      catechin, (-)-epigallocatechin-3-O-(3-O-methyl)gallate.
AB  - The aim of this research was to identify tea varieties containing high levels of
      catechin methyl ester that could be used as important sources for genetic
      breeding and in the production of high quality tea. We examined 113 species that
      have been preserved in the Taitung Branch of the Tea Research and Extension
      Station of Taiwan (TTES). The average level of (-)-epigallocatechin-3-O-(3-O
      methyl) gallate (EGCG3''Me) was 0.45% for all varieties screened. Among them, 16
      varieties with higher EGCG3''Me content (>0.8%) were considered good candidates
      for manufacturing partially fermented tea. Analysis of these tea varieties
      revealed that the EGCG3''Me content in leaves did not correlate with the caffeine
      content. Genetic assessments revealed that the lengths of their internal
      transcribed spacers (ITS) were in the range of 638-670 bp and that the sequence
      identities were in the range of 0.690-1. Two major groups were constructed by
      phylogenetic analysis, I and II, with a genetic distance of 0.08 based on the
      ITS1-5.8S-ITS2 sequences between the ribosomal genes. Our results provide genetic
      information about tea varieties with elevated EGCG3''Me content and indicate the
      need for a comprehensive genetic assessment of tea germplasms preserved in the
      TTES to better serve the future of tea breeding.

PMID- 19761186
TI  - Spectroscopic and theoretical studies of transition metal oxides and dioxygen
      complexes.

PMID- 19761188
TI  - Simultaneous determination of melamine and 5-hydroxymethylfurfural in milk by
      capillary electrophoresis with diode array detection.
AB  - This article describes the development of a simple analytical approach for the
      simultaneous determination of melamine and 5-hydroxymethylfurfural (HMF) in milk
      samples using capillary electrophoresis (CE) with diode array detection (DAD) for
      the first time. Ultraviolet absorption at wavelengths of 214 and 280 nm was
      applied for the detection of melamine and HMF, respectively. Milk samples were
      extracted with 1% trichloroacetic acid using a high-speed blender and
      ultrasonication. After centrifugation and filtration, the extract was analyzed by
      CE-DAD directly. Micellar electrokinetic capillary chromatography was employed as
      the separation mode by adding sodium dodecyl sulfate (SDS) to the electrolyte.
      Under optimal separation conditions, melamine, HMF, and interferents were well
      resolved. The linear dynamic ranges were 0.05-100 microg/mL for melamine (R(2) =
      0.9996) and 0.1-100 microg/mL for HMF (R(2) = 0.9997). The assay detection limits
      were 0.047 microg/mL and 0.067 microg/mL for melamine and HMF, respectively.
      Satisfactory results were obtained for the assay recovery rate and repeatability.
      The proposed method was successfully applied for the analysis of melamine and HMF
      in real milk samples, and the results of melamine were comparable to those
      obtained using HPLC-UV reference method.

PMID- 19761189
TI  - Phytochemical profiles of different mulberry (Morus sp.) species from China.
AB  - Mulberry is rich in alkaloids, polyphenols, flavonoids, and anthocyanins, which
      have been suggested to be responsible for health benefits. The concentrations of
      1-deoxynojirimycin (DNJ), resveratrol, oxyresveratrol, cyanidin-3-O-beta
      glucoside (Cy-3-glu), cyanidin-3-O-beta-rutinoside (Cy-3-rut), and rutin in
      mulberry juice, fruits, and leaves of 8 species grown in China were examined. It
      is the first time content determination of DNJ in mulberry juice and
      oxyresveratrol in mulberry fruits and leaves has been reported. Among the
      varieties tested, Da 10 (Morus atropurpurea Roxb.) was the most valuable cultivar
      considering its high content of functional components. Besides, Hetianbaisang (M.
      alba Linn.), Taiwanguosang (M. atropurpurea Roxb.), Fujian 2 hao (M. alba Linn.),
      Gaozhoujisang (M. australis Poir.), and Shanxiguosang (M. nigra Linn.) were rich
      in DNJ, resveratrol, oxyresveratrol, anthocyanins, and flavonoids, respectively.
      The high contents of functional compounds in mulberry juice, fruits, and leaves
      implied that they might be potential resources for the development of functional
      drinks and food.

PMID- 19761190
TI  - Particle focusing mechanisms in curving confined flows.
AB  - Particles in finite-inertia confined channel flows are known to segregate and
      focus to equilibrium positions whose number corresponds with the fold of symmetry
      of the channel's cross section. The addition of curvature into channels
      presumably modifies these equilibrium inertial focusing positions, because of the
      secondary flow induced in curved channels. Here, we identify the critical
      interaction of the secondary flow field with inertial lift forces to create
      complex sets of particle focusing positions that vary with the channel Reynolds
      number (Re(C)) and the inertial force ratio, which is a new dimensionless
      parameter that is based on the ratio of inertial lift to drag forces from the
      secondary flow. We use these results to identify microfluidic channel geometries
      to focus particles at rates an order of magnitude higher than previously shown
      (channel Reynolds number, Re(C) = 270) and develop design criteria for the
      focusing of potentially arbitrary-sized particles. In addition, our results
      indicate that channel curvature can lead to microfluidic designs with reduced
      fluidic resistance, useful for lower power inertial focusing or separation. These
      results will enable design of practical particle/cell separation, filtration, and
      focusing systems for critical applications in biomedicine and environmental
      cleanup.

PMID- 19761192
TI  - Simple chiral chain dienes as ligands for Rh(I)-catalyzed conjugated additions.
AB  - This paper describes that a simple and readily available chain diene (3R,4R)-hexa
      1,5-diene-3,4-diol (L1) was successfully utilized as a novel steering ligand for
      Rh(I)-catalyzed asymmetric conjugated additions. Encouraging yields and ee's have
      been achieved, which may provide a new and practical direction for designing
      chiral diene ligands in the future.

PMID- 19761191
TI  - HFT-T, a targeting nanoparticle, enhances specific delivery of paclitaxel to
      folate receptor-positive tumors.
AB  - Nonspecific distribution of chemotherapeutic drugs (such as paclitaxel) is a
      major factor contributing to side effects and poor clinical outcomes in the
      treatment of human head and neck cancer. To develop novel drug delivery systems
      with enhanced efficacy and minimized adverse effects, we synthesized a ternary
      conjugate heparin-folic acid-paclitaxel (HFT), loaded with additional paclitaxel
      (T). The resulting nanoparticle, HFT-T, is expected to retain the antitumor
      activity of paclitaxel and specifically target folate receptor (FR)-expressing
      tumors, thereby increasing the bioavailability and efficacy of paclitaxel. In
      vitro experiments found that HFT-T selectively recognizes FR-positive human head
      and neck cancer cell line KB-3-1, displaying higher cytotoxicity compared to the
      free form of paclitaxel. In a subcutaneous KB-3-1 xenograft model, HFT-T
      administration enhanced the specific delivery of paclitaxel into tumor tissues
      and remarkably improved antitumor efficacy of paclitaxel. The average tumor
      volume in the HFT-T treatment group was 92.9 +/- 78.2 mm(3) vs 1670.3 +/- 286.1
      mm(3) in the mice treated with free paclitaxel. Furthermore, paclitaxel tumors
      showed a resurgence of growth after several weeks of treatment, but this was not
      observed with HFT-T. This indicates that HFT-T could be more effective in
      preventing tumors from developing drug resistance. No significant acute in vivo
      toxicity was observed. These results indicate that specific delivery of
      paclitaxel with a ternary structured nanoparticle (HFT-T) targeting FR-positive
      tumor is a promising strategy to enhance chemotherapy efficacy and minimize
      adverse effects.

PMID- 19761193
TI  - Iterative synthesis of (oligo)deoxypropionates via zinc-catalyzed enantiospecific
      sp3-sp3 cross-coupling.
AB  - This group's recently reported mild zinc-catalyzed enantiospecific sp3-sp3 cross
      coupling of lactic acid tert-butylester triflate with Grignard reagents was now
      applied to an iterative approach in the synthesis of a series of all four
      possible diastereomers of the shown trideoxypropionate. Oligodeoxypropionate
      structures are a common motif in a large number of biologically relevant natural
      products of polyketide origin thus making our approach a versatile tool in their
      synthesis.

PMID- 19761194
TI  - Formation of straight 10 nm diameter silicon nanopores in gold decorated silicon.
AB  - We observe pore formation with diameters in the 10 nm range in silicon when it is
      covered with gold particles. This pore etching occurs when the sample is put in 5
      wt % hydrofluoric acid (HF) solution for a few minutes. The pores form along the
      100 direction, which is also the preferred direction of macro- and mesopores
      electrochemically etched into silicon. No etching occurs if the dissolved oxygen
      is removed from the aqueous HF solution or the gold is removed from the silicon
      surface. This leads to the assumption that the dissolved oxygen acts as an
      oxidant as in the case of stain etching with gold as cathodic material. A
      tentative model is suggested to explain why all of the observed nanopores have
      roughly the same diameter of about 10 nm. These pores can occur for
      inhomogeneously gold-covered planar silicon surfaces but also in MBE (molecular
      beam epitaxy) grown silicon nanowires since these nanowires are covered
      unintentionally with gold nanoclusters at their cylindrical surface.

PMID- 19761195
TI  - Li(12)Si(60)H(60) fullerene composite: a promising hydrogen storage medium.
AB  - By using the first-principles DFT calculations, we design a novel hydrogen
      storage material, Li(12)Si(60)H(60) composite, and validate its geometric
      stability. It is found that the adsorbed Li atoms do not cluster on the
      Si(60)H(60) fullerene unlike other metals such as Ti, owing to the relatively low
      Li-Li binding energy and the inhibition of Si-H bonds. Our results show that the
      Li-doping enhances the hydrogen adsorption ability of Si(60)H(60) significantly,
      owing to the charge transfer from the doped Li atoms to the host material and the
      polarization of the adsorbed H(2) molecules. By combining the first-principles
      calculation and grand canonical Monte Carlo simulation, we further investigate
      the hydrogen storage capacity of the simulation-synthesized exohedral
      Li(12)Si(60)H(60) composite at T = 77 K. As the vdW gap (i.e., the separation
      between the surfaces of two Li(12)Si(60)H(60) fullerenes) is equal to 8.2 A, the
      total hydrogen uptake of the square-arranged Li(12)Si(60)H(60) array reaches
      12.83 wt % at p = 10 MPa, while the excess hydrogen uptake shows a maximum of
      7.46 wt % at p = 6 MPa. Impressively, at T = 298 K and p = 10 MPa, the
      Li(12)Si(60)H(60) array still exhibits a total hydrogen uptake of 3.88 wt % at
      the vdW gap of 8.2 A. These results clearly indicate that the composite,
      Li(12)Si(60)H(60) fullerene, is a promising candidate for hydrogen storage.

PMID- 19761196
TI  - Theoretical Study of the Jahn-Teller effect in CH3CN+ (X2E) and CD3CN+ (X2E):
      multimode spin-vibronic energy level calculations.
AB  - The spin-vibronic energy levels for CH(3)CN(+)(X(2)E) and CD(3)CN(+)(X(2)E) have
      been calculated using a diabatic model including multimode vibronic couplings and
      spin-orbit interaction without adjusting any parameter. The diabatic potential
      energy surfaces are represented by the Taylor expansions including linear,
      quadratic and bilinear vibronic coupling terms. The normal coordinates used in
      the Taylor expansion were expressed by the mass-weighted Cartesian coordinates.
      The adiabatic potential energy surfaces for CH(3)CN(+) and CD(3)CN(+) were
      calculated at the level of CASPT2/cc-pvtz, and the spin-orbit coupling constant
      was calculated at the level of MRCI/CAS/cc-pvtz. The spin-orbit energy splittings
      for the ground vibrational states of CH(3)CN(+)(X(2)E) and CD(3)CN(+)(X(2)E) are
      20 and 16 cm(-1), respectively, which are resulted from the quenching of the spin
      orbit coupling strength of 51 cm(-1). The calculated spin-vibronic levels are in
      good agreement with the experimental data. The calculation results show that the
      Jahn-Teller effects in CH(3)CN(+)(X(2)E) and CD(3)CN(+)(X(2)E) are essential to
      understand their spin-vibronic energy structure.

PMID- 19761197
TI  - Effect of hydrogen bonding on the rotational and translational dynamics of a
      headgroup-bound chromophore in bilayer lipid membranes.
AB  - We have studied the interactions of the chromophore 1,2-dioleoyl-sn-glycero-3
      phosphoethanolamine-N-7-nitro-2-1,3-benzoxadiazol-4-yl (18:1 NBD-PE) imbedded in
      the headgroup region of bilayer lipid membranes consisting of 1,2-dioleoyl-sn
      glycero-3-phosphocholine (DOPC) and 1,2-dioleoyl-sn-glycero-3-[phospho-rac-(1
      glycerol)] (DOPG). We have examined the molecular and mesoscale dynamics of the
      chromophore using time-correlated single photon counting (TCSPC) to measure
      rotational diffusion dynamics in lipid vesicles and fluorescence recovery after
      pattern photobleaching (FRAPP) to determine translational diffusion coefficients
      and mobile fractions in supported lipid bilayers. TCSPC data reveal that
      chromophore rotational diffusion rates in DOPG vesicles are statistically the
      same as in DOPC and mixed DOPC/DOPG vesicles, suggesting that the NBD-PE
      chromophore does not interact strongly with the headgroup region of these
      bilayers; however, FRAPP experiments show that lateral diffusion is statistically
      lower in mixed DOPC/DOPG-supported bilayers than in DOPC-supported bilayers.
      These results suggest that bilayers containing DOPG likely undergo interlipid
      headgroup hydrogen bonding interactions that suppress translational diffusion.

PMID- 19761198
TI  - Theoretical insight on the S --> O photoisomerization of DMSO complexes of
      Ru(II).
AB  - Complexes of the type [Ru(tpy)(L)(dmso)](n+) (where tpy = 2,2':6',2''
      terpyridine; L = 2,2'-bipyridine (bpy), n = 2; N,N,N',N'-tetramethylethylene
      diamine (tmen), n = 2; acetylacetonate (acac), n = 1; oxalate (ox), n = 0;
      malonate (mal), n = 0) were investigated by density functional theory (DFT). The
      results do not support a promoting role for the dsigma* ligand field (LF) states
      during excited state S --> O isomerization. Instead, the calculations show that
      the formation of a Ru(III) center is important in the isomerization, along with
      the identity of the ancillary bidentate ligand. The present work shows that the
      orbital contributions from the bidentate ligand to the HOMO, which is typically
      centered on the ruthenium, plays an important role in the photochemical and
      oxidative reactivity of the complexes.

PMID- 19761199
TI  - Quantum-chemical description of the thermodynamic characteristics of
      clusterization of melamine-type amphiphiles at the air/water interface.
AB  - The semiempiric PM3 method is used to calculate the thermodynamic parameters of
      the formation of monomers, dimers, trimers, and tetramers of the amphiphilic
      melamine-type series of 2,4-di(n-alkylamino)-6-amino-1,3,5-triazine (2C(n)H(2n+1)
      melamine) with n = 9-16. The most stable conformations are determined, which then
      are used to construct the clusters. The peculiar feature of these structures is
      the existence of a bend at one of the alkyl chains. Thus, the formation of
      infinite films becomes possible because of their spatial arrangement. From the
      calculation of the relative amount of various conformers in the mixture, it
      follows that, if the alkyl chain length is lower than 11-12 carbon atoms, the
      mixture is composed mainly of the monomers that do not contain any intramolecular
      interactions, whereas for higher alkyl chain lengths the monomers that involve
      such interactions prevail in the mixture. For all clusters thus considered, the
      thermodynamic parameters (enthalpies, entropies, and Gibbs' energies) of
      clusterization are calculated. It is shown that the dependencies of these
      parameters on the alkyl chain length either exhibit stepwise shape or are
      represented by the combination of a linear and stepwise function. This depends on
      the different number of hydrogen-hydrogen interactions in the structures
      considered. Five types of clusters that are capable of the formation of infinite
      2D films are considered in detail. For each of these types, the dependencies of
      the clusterization enthalpy, entropy, and Gibbs' energy on the alkyl chain length
      in the constituting monomers are derived. Using these dependencies, it becomes
      possible to calculate these thermodynamic characteristics for clusters of any
      size, and also for infinite 2D films. It is shown that the spontaneous
      clusterization of 2C(n)H(2n+1)-melamine becomes possible if the alkyl chain
      length exceeds 9 carbon atoms.

PMID- 19761200
TI  - Biochemical characterization of the multidrug regulator QacR distinguishes
      residues that are crucial to multidrug binding and induction of qacA
      transcription.
AB  - Staphylococcus aureus transcription factor QacR regulates expression of the qacA
      multidrug efflux determinant. In response to binding cationic lipophilic
      compounds, including ethidium and rhodamine 6G, QacR dissociates from the qacA
      operator alleviating repression. Such ligand binding uniformly induces a coil-to
      helix transition of residues Thr(89)-Tyr(93) revealing an asymmetric binding
      pocket in QacR containing two distinct subpockets. Here, the functional
      significance of hydrophobic, aromatic, and polar residues characteristic of the
      rhodamine 6G pocket and the proximal Tyr(92), proposed to facilitate the
      transcriptionally active conformation, was examined. Notably, the presence of
      Tyr(92) was not essential for QacR structural changes between DNA-bound and
      induced conformations. Furthermore, although mutation of the majority of residues
      contacting rhodamine 6G exerted moderate effects on QacR-rhodamine 6G binding,
      mutation of Leu(54) and Gln(96), and cumulative mutations involving these with
      Tyr(93) and Tyr(123), imparted a dramatic decrease in QacR-rhodamine 6G binding
      affinity. This equated with impaired dissociation of QacR from its operator DNA
      in the presence of this ligand in S. aureus, delineating the important role of
      these residues in the QacR-rhodamine 6G interaction. Additionally, despite
      maintaining a high affinity for ethidium, QacR mutants involving Leu(54),
      Tyr(93), Gln(96), and Tyr(123), which denote the interface between the rhodamine
      6G and ethidium subpockets, were unable to be induced from operator DNA in the
      presence of ethidium in S. aureus. This highlights the significant contribution
      of these residues to QacR-mediated derepression of qacA transcription following
      ligand binding in the distal subpocket and may be important for the general
      mechanism irrespective of the ligand bound.

PMID- 19761201
TI  - Novel method for generating structure-based pharmacophores using energetic
      analysis.
AB  - We describe a novel method to develop energetically optimized, structure-based
      pharmacophores for use in rapid in silico screening. The method combines
      pharmacophore perception and database screening with protein-ligand energetic
      terms computed by the Glide XP scoring function to rank the importance of
      pharmacophore features. We derive energy-optimized pharmacophore hypotheses for
      30 pharmaceutically relevant crystal structures and screen a database to assess
      the enrichment of active compounds. The method is compared to three other
      approaches: (1) pharmacophore hypotheses derived from a systematic assessment of
      receptor-ligand contacts, (2) Glide SP docking, and (3) 2D ligand fingerprint
      similarity. The method developed here shows better enrichments than the other
      three methods and yields a greater diversity of actives than the contact-based
      pharmacophores or the 2D ligand similarity. Docking produces the most cases
      (28/30) with enrichments greater than 10.0 in the top 1% of the database and on
      average produces the greatest diversity of active molecules. The combination of
      energy terms from a structure-based analysis with the speed of a ligand-based
      pharmacophore search results in a method that leverages the strengths of both
      approaches to produce high enrichments with a good diversity of active molecules.

PMID- 19761202
TI  - Computational calculation of equilibrium constants: addition to carbonyl
      compounds.
AB  - Hydration reactions are relevant for understanding many organic mechanisms. Since
      the experimental determination of hydration and hemiacetalization equilibrium
      constants is fairly complex, computational calculations now offer a useful
      alternative to experimental measurements. In this work, carbonyl hydration and
      hemiacetalization constants were calculated from the free energy differences
      between compounds in solution, using absolute and relative approaches. The
      following conclusions can be drawn: (i) The use of a relative approach in the
      calculation of hydration and hemiacetalization constants allows compensation of
      systematic errors in the solvation energies. (ii) On average, the methodology
      proposed here can predict hydration constants within +/- 0.5 log K(hyd) units for
      aldehydes. (iii) Hydration constants can be calculated for ketones and carboxylic
      acid derivatives within less than +/- 1.0 log K(hyd), on average, at the CBS-Q
      level of theory. (iv) The proposed methodology can predict hemiacetal formation
      constants accurately at the MP2 6-31++G(d,p) level using a common reference. If
      group references are used, the results obtained using the much cheaper DFT-B3LYP
      6-31++G(d,p) level are almost as accurate. (v) In general, the best results are
      obtained if a common reference for all compounds is used. The use of group
      references improves the results at the lower levels of theory, but at higher
      levels, this becomes unnecessary.

PMID- 19761203
TI  - The crossed [2+2] cycloaddition of 1-phenylcyclopropene and 1-bromo-2
      phenylcyclopropene.
AB  - 1-Bromo-2-phenylcyclopropene (2) underwent [2+2] dimerization to generate 1,2
      dibromo-4,5-diphenyltricyclo[3.1.0.0(2,4)]hexane (5), which was heated to form
      1,2-dibromo-4,5-diphenylcyclohexa-1,4-diene (6) followed by oxidation to yield
      4',5'-dibromo-o-terphenyl (7). o-Terphenyl 7 could be synthesized in one-pot
      reactions from 1,1,2-tribromocyclopropane (3). When cyclopropane 3 was treated
      with 1.5 equiv of methyllithium followed by slowly adding the proton source,
      crossed [2+2] adduct 8 was isolated in 40% yield. Compound 8 was heated and
      oxidated to produce 4'-bromo-o-terphenyl (11).

PMID- 19761204
TI  - [1,2]-Anionic rearrangement of 2-benzyloxypyridine and related pyridyl ethers.
AB  - An anionic rearrangement of 2-benzyloxypyridine is described. Pyridine-directed
      metalation of the benzylic carbon leads to 1,2-migration of pyridine via a
      postulated associative mechanism (addition/elimination). Several aryl pyridyl
      carbinols were obtained in high yields. A formal synthesis of carbinoxamine, an
      antihistamine drug used for the treatment of seasonal allergies and hay fever,
      emerges from this methodology.

PMID- 19761205
TI  - Effect of cholesterol on the formation and hydration behavior of solid-supported
      niosomal membranes.
AB  - The effect of cholesterol on the formation and hydration behavior of solid
      supported polysorbate 20 (Tween 20)/cholesterol self-assemblies was investigated
      by means of in situ energy-dispersive X-ray diffraction in a wide range of
      relative humidity (0.4 < RH < 1). At low hydration, Tween 20 and cholesterol were
      found to demix, with the latter molecules forming crystallites with a
      pseudobilayer structure (d approximately = 34 A). Water adsorption promoted the
      progressive solubilization of cholesterol crystallites. When in the presence of
      enough cholesterol, the formation of niosomal bilayer membranes rich in Tween 20
      occurred (RH approximately = 0.985). Upon further hydration, two distinct regimes
      associated with remarkable changes in the niosomal membrane structure were
      identified. In the first regime (0.985 < RH < 0.988), the swelling of the
      lamellar d spacing was due to the enlargement of the membrane thickness. In the
      second regime, the structure of Tween 20/cholesterol membranes was quite
      insensitive to hydration, and the thickness of the intermembrane water layer
      increased substantially. Remarkably, the curve of the calculated number of waters
      per surfactant molecule showed a distinct break at RH approximately 0.988,
      suggesting that the observed structural change in niosomal membranes was most
      likely due to the completion of the filling of the Tween 20 hydration shell. At
      full hydration, niosomal membranes exhibited the same lamellar d spacing of
      niosomes vesicles in aqueous solution. The process completely reversed upon
      dehydration.

PMID- 19761206
TI  - Discovering the complex chemistry of a simple Ni(II)/H(3)L system:
      magnetostructural characterization and DFT calculations of Di- and polynuclear
      nickel(II) compounds.
AB  - The simple nickel(II) acetate/H(3)L system (H(3)L = 2-(2-hydroxyphenyl)-1,3-bis[4
      (2-hydroxyphenyl)-3-azabut-3-enyl]-1,3-imidazolidine) presents an unusually
      complicated reactivity scheme, which strongly depends on the Ni(OAc)(2)/H(3)L
      molar ratio and on the pH of the medium. Thus, in addition to the formerly
      reported compounds [Ni(2)L(OAc)(H(2)O)(2)][Ni(2)L(OAc)(H(2)O)(HOAc)].3.25H(2)O,
      1.3.25H(2)O;
      [{Ni(3)L(OAc)(OH)(H(2)O)(MeOH)(2)}(CO(3)){Ni(2)L(OAc)(MeOH)(2)}].2.7H(2)O.1.5MeOH
      2.2.7H(2)O.1.5MeOH; and [Ni(3)L(OAc)(2)(OH)(H(2)O)(MeOH)(2)].3H(2)O.0.5MeOH,
      3.3H(2)O.0.5MeOH, this system can also yield some other complexes as [Ni(2)L(o-O
      C(6)H(4)-CHO)(H(2)O)].1.75H(2)O, 4.1.75H(2)O;
      [Ni(2)L(OH)(H(2)O)(MeOH)].3H(2)O.1.5MeOH, 5.3H(2)O.1.5MeOH;
      [Ni(2)L(OAc)(MeOH)(2)].H(2)O.3MeOH, 6.H(2)O.3MeOH; and
      [{Ni(2)L(MeOH)}(CO(3)){Ni(2)L(MeOH)(2)}].4.75H(2)O.2MeOH, 7.4.75H(2)O.2MeOH. A
      detailed study of the reaction scheme that allows obtaining all of these
      complexes is presented herein, as well as the structural characterization of the
      novel compounds 4.1.75H(2)O to 7.4.75H(2)O.2MeOH. X-ray analyses show that all of
      them present stereoisomery in the solid state. In this way, 6.H(2)O.3MeOH appears
      particularly interesting, as its molecular and supramolecular chirality is only
      controlled by hydrogen bonds. Magnetic studies of 5.3H(2)O to 7.4.75H(2)O.2MeOH
      are also discussed, and the complicated magnetic superexchange pathway shown by
      7.4.75H(2)O.2MeOH is analyzed in light of DFT calculations.

PMID- 19761207
TI  - Development of a functionalized polymer for stent coating in the arterial
      delivery of small interfering RNA.
AB  - In patients receiving drug eluting stents, there is a growing concern about both
      the long-term toxicity/degradability of the polymers used for the coating, and
      the nature of the therapeutic agents. We hypothesized that the use of a
      functionalized biocompatible polymer for a stent coating could be appropriate for
      local arterial therapy. A cationized pullulan hydrogel was thus prepared to cover
      bare metal stents that could be further loaded with small interfering RNA (siRNA)
      targeted at MMP2 for gene silencing in vascular cells. The efficient coverage of
      the stent struts by a smooth polymeric layer, which can withstand the crimping of
      the stent on a balloon-catheter and its deployment, was demonstrated by
      fluorescence microscopy, scanning electron microscopy, and atomic force
      microscopy. The release of siRNA from the stents was modulated by the presence of
      the cationic groups, as compared to noncationized pullulan hydrogel. In vivo
      implantation of coated stents was successful and cationized pullulan-based
      hydrogels loaded with siRNA in rabbit balloon-injured carotid arteries induced an
      uptake of siRNA into the arterial wall and a decrease of pro-MMP2 activity. These
      results suggest that cationized pullulan-based hydrogel could be used as a new
      biocompatible and biodegradable stent coating for local gene therapy in the
      arterial wall.

PMID- 19761208
TI  - C-nucleosides: synthetic strategies and biological applications.

PMID- 19761209
TI  - Efficiency of a NPK fertilizer with adhered zinc lignosulfonate as a zinc source
      for maize (Zea mays L.).
AB  - The aim of this work was to evaluate the efficiency of a NPK fertilizer (8:15:15)
      with a Zn lignosulfonate (ZnLS) adhered as Zn source for maize plants. This
      product was compared in three experimental designs with the same NPK fertilizer
      with ZnSO(4) adhered and with no Zn adhered. The first and the second assays were
      carried out in a growth chamber by using perlite and a calcareous soil as
      substrate and the third experiment was raised in two calcareous fields. In
      general, growth chamber experiments showed that plants treated with NPK + ZnLS
      presented the highest dry weight and Zn concentrations in shoots. Also at field
      experiments, the Zn concentration in shoots was significantly high in plants
      treated with NPK + ZnLS. The grain harvested showed that this treatment gave the
      highest values in one location, but in the other no significant differences were
      observed. Although further research is required, we can conclude that NPK + ZnLS
      product could be a suitable source of Zn for maize crops.

PMID- 19761210
TI  - Insulin secretagogue bioactivity of finger citron fruit (Citrus medica L. var.
      Sarcodactylis Hort, Rutaceae).
AB  - Finger citron [Citrus medica L. var. Sarcodactylis Hort, Rutaceae] (FC) fruits,
      widely cultivated in Japan, the southern provinces of China and Taiwan, are
      commonly used as functional vegetables and preserved as sweetmeats. Previously we
      identified the major compounds in essential oils (% in EO) of FC fruits to be d
      limonene (51.24), gamma-terpenene (33.71), alpha-pinene (3.40), and beta-pinene
      (2.88). Documented evidence on its insulin secretion characteristics is still
      lacking. In parallel to compositional analysis, we performed in vivo the safety,
      hypoglycemic, and antidiabetic tests in Sprague-Dawley-SPF rats and Wistar DIO
      rats respectively. By kinetic analysis on the hypoglycemic patterns of the
      intraperitoneal glucose tolerance (IPGTT) and the insulin-glucose tolerance tests
      (IGTT), its insulin secretagogue effect was confirmed. In conclusion, FC fruits
      that concomitantly possess insulin secretagogue and slimming effects would be
      very beneficial to type 2 diabetes mellitus patients.

PMID- 19761211
TI  - Dietary krill oil supplementation reduces hepatic steatosis, glycemia, and
      hypercholesterolemia in high-fat-fed mice.
AB  - Krill oil (KO) is rich in n-3 fatty acids that are present in phospholipids
      rather than in triglycerides. In the present study, we investigated the effects
      of dietary KO on cardiometabolic risk factors in male C57BL/6 mice fed a high-fat
      diet. Mice (n = 6-10 per group) were fed for 8 weeks either: (1) a nonpurified
      chow diet (N); (2) a high-fat semipurified diet containing 21 wt % buttermilk +
      0.15 wt % cholesterol (HF); (3) HF supplemented with 1.25 wt % KO (HFKO1.25); (4)
      HF with 2.5 wt % KO (HFKO2.5); or (5) HF with 5 wt % KO (HFKO5.0). Dietary KO
      supplementation caused a significant reduction in liver wt (i.e., hepatomegaly)
      and total liver fat (i.e., hepatic steatosis), due to a dose-dependent reduction
      in hepatic triglyceride (mean +/- SEM: 35 +/- 6, 47 +/- 4, and 51 +/- 5% for
      HFKO1.25, -2.5, and -5.0 vs HF, respectively, P < 0.001) and cholesterol (55 +/-
      5, 66 +/- 3, and 71 +/- 3%, P < 0.001). Serum cholesterol levels were reduced by
      20 +/- 3, 29 +/- 4, and 29 +/- 5%, and blood glucose was reduced by 36 +/- 5, 34
      +/- 6, and 42 +/- 6%, respectively. Serum adiponectin was increased in KO-fed
      animals (HF vs HFKO5.0: 5.0 +/- 0.2 vs 7.5 +/- 0.6 microg/mL, P < 0.01). These
      results demonstrate that dietary KO is effective in improving metabolic
      parameters in mice fed a high-fat diet, suggesting that KO may be of therapeutic
      value in patients with the metabolic syndrome and/or nonalcoholic fatty liver
      disease.

PMID- 19761213
TI  - Spirodiepoxides: synthesis of epoxomicinoids.
AB  - Three closely related analogues of epoxomicin have been synthesized. Allene
      derived spirodiepoxides were key intermediates. Spirodiepoxide formation and
      stereochemical dependence on solvent, oxidant, and allene structure were
      cataloged. The facial selectivity of the first epoxidation of 1,3-disubstituted
      and trisubstituted allenes was found to be >20:1 with dimethyldioxirane in
      chloroform. For stereogenic allenes, the facial selectivity of the second
      oxidation is dependent primarily on allene structure and secondarily on solvent
      and oxidant. For the acyclic systems evaluated this ratio was as high as 8:1. A
      conformational model is advanced to account for these observations.

PMID- 19761212
TI  - Structure mechanism insights and the role of nitric oxide donation guide the
      development of oxadiazole-2-oxides as therapeutic agents against schistosomiasis.
AB  - Schistosomiasis is a chronic parasitic disease affecting hundreds of millions of
      individuals worldwide. Current treatment depends on a single agent, praziquantel,
      raising concerns of emergence of resistant parasites. Here, we continue our
      explorations of an oxadiazole-2-oxide class of compounds we recently identified
      as inhibitors of thioredoxin glutathione reductase (TGR), a selenocysteine
      containing flavoenzyme required by the parasite to maintain proper cellular redox
      balance. Through systematic evaluation of the core molecular structure of this
      chemotype, we define the essential pharmacophore, establish a link between the
      nitric oxide donation and TGR inhibition, determine the selectivity for this
      chemotype versus related reductase enzymes, and present evidence that these
      agents can be modified to possess appropriate drug metabolism and pharmacokinetic
      properties. The mechanistic link between exogenous NO donation and parasite
      injury is expanded and better defined. The results of these studies verify the
      utility of oxadiazole-2-oxides as novel inhibitors of TGR and as efficacious
      antischistosomal agents.

PMID- 19761214
TI  - Material degradomics: on the smell of old books.
AB  - We successfully transferred and applied -omics concepts to the study of material
      degradation, in particular historic paper. The main volatile degradation products
      of paper, constituting the particular "smell of old books", were determined using
      headspace analysis after a 24 h predegradation procedure. Using supervised and
      unsupervised methods of multivariate data analysis, we were able to
      quantitatively correlate volatile degradation products with properties important
      for the preservation of historic paper: rosin, lignin and carbonyl group content,
      degree of polymerization of cellulose, and paper acidity. On the basis of
      volatile degradic footprinting, we identified degradation markers for rosin and
      lignin in paper and investigated their effect on degradation. Apart from the
      known volatile paper degradation products acetic acid and furfural, we also put
      forward a number of other compounds of potential interest, most notably lipid
      peroxidation products. The nondestructive approach can be used for rapid
      identification of degraded historic objects on the basis of the volatile
      degradation products emitted by degrading paper.

PMID- 19761215
TI  - Selective detection of diethylene glycol in toothpaste products using neutral
      desorption reactive extractive electrospray ionization tandem mass spectrometry.
AB  - A rapid, sensitive method based on neutral desorption (ND) reactive extractive
      electrospray ionization mass spectrometry (EESI-MS) has been established for the
      selective quantitative detection of diethylene glycol (DEG) in toothpaste
      products without any sample pretreatment. The sensitivity and specificity of DEG
      detection were enhanced by implementing selective ion/molecule reactions in the
      EESI process, featuring the EESI mass spectra with the characteristic signals of
      DEG. The method provided a low limit of detection (LOD) (approximately 0.00002%,
      weight percent of DEG in toothpaste), reasonable recovery (97.6-102.4%), and
      acceptable relative standard deviations (RSD < 8%, n = 8) for direct measuring of
      DEG in the spiked toothpaste samples. Trace amounts of DEG in commercial
      toothpaste products have been quantitatively detected without any sample
      manipulation. The results demonstrate that nonvolatile compounds such as DEG can
      be sensitively liberated using the neutral gas beam for quantitative detection
      from the extremely viscous toothpaste containing solid nanoparticles, showing
      that ND-EESI-MS is a useful tool for the rapid characterization of highly complex
      and/or viscous samples at molecular levels.

PMID- 19761216
TI  - Structure, dynamics, and hydration of a collagen model polypeptide, (L-prolyl-L
      prolylglycyl)10, in aqueous media: a chemical equilibrium analysis of triple
      helix-to-single coil transition.
AB  - The structure, dynamics, and hydration behavior of a collagen model polypeptide,
      (L-prolyl-L-prolylglycyl)(10) (PPG10), were investigated in pure water and dilute
      acetic acid over a wide temperature range using broadband dielectric relaxation
      (DR) techniques that spanned frequencies from 1 kHz to 20 GHz. All samples showed
      pronounced dielectric dispersion with two major relaxation processes around 3 MHz
      and 20 GHz. Because DR measurements sensitively probe dipoles and their dynamics,
      the structures and ionization states of the carboxy and amino termini of aqueous
      PPG10 were precisely determined from the relaxation times and strengths in the 3
      MHz frequency range. In solution, PPG10 formed mixtures of monodisperse rods as
      triple helices with lengths and diameters of 8.6 and 1.5 nm, respectively, and
      monomeric random coils with radii of approximately 1.4 nm. Ionization of the C
      terminus was suppressed by the addition of acetic acid in both states. The
      fraction of random coils (f(coil)) was found to be a function of temperature (T)
      and the concentration of PPG10 (c). At low temperatures, small f(coil) values
      were found, which increased with temperature to reach f(coil) = 1 at
      approximately 60 degrees C, irrespective of c. This phenomenon, well-known as a
      triple helix-to-single coil transition, is discussed on the basis of the chemical
      reaction, (PPG10)(3) <==> 3PPG10, with an equilibrium constant of K =
      3(c/55.6)(2)f(coil)(3)(1 - f(coil))(-1). The standard enthalpy change evaluated
      from Arrhenius plots (ln K versus T(-1)) was found to change dramatically at the
      same transition temperature that was previously determined by using optical
      rotation experiments. The other major DR process, observed at approximately 20
      GHz, was assigned to free and hydrated water molecules and used to determine the
      average hydration number (m) per PPG10. The m values for the triple helix and
      random coil state at 25 degrees C were evaluated to be m(th) = 60-70 and m(coil)
      = 250-270. The m(th) value was in reasonable agreement with the number of
      hydrated water molecules in crystals of (PPG10)(3) residing in the first and
      second hydration shells around the amino acid residues. This agreement suggests
      that the structure of the triple helix in crystals is very similar to that in
      aqueous solution, including the location of hydrated water molecules.

PMID- 19761217
TI  - Effect of peptide-to-TiO2 beads ratio on phosphopeptide enrichment selectivity.
AB  - Titanium dioxide (TiO(2)) has been proven to be a highly efficient strategy and
      widely used for phosphopeptide enrichment. Many advances have been made recently,
      including online/offline mode and optimization of sample loading/elution buffer;
      however, beads usage has rarely been explored. In the current study, we found
      that the peptide-to-TiO(2) beads ratio was a significant factor for
      phosphopeptide enrichment, and insufficient or excessive beads could decrease the
      selectivity. Specifically, for HeLa total cell lysate, the optimum peptide-to
      beads ratio is about 1:2-1:8 (mass/mass) to obtain the highest enrichment
      selectivity and the maximum phosphopeptides identification with single
      incubation. Pre-experiments are recommended to decide an optimum peptide-to
      TiO(2) beads ratio when it comes to different samples. Interestingly, deficient
      beads can help identify much more multiphosphorylated peptides than the optimum
      peptide-to-beads ratio by consecutive incubations. Therefore, if
      multiphosphorylated peptides identification is desired, deficient beads amount is
      preferred. In addition, consecutive incubation using deficient beads could be
      used as a fractionation of phosphopeptides besides as an enrichment method.

PMID- 19761218
TI  - Oligosaccharide binding in Escherichia coli glycogen synthase.
AB  - Glycogen/starch synthase elongates glucan chains and is the key enzyme in the
      synthesis of glycogen in bacteria and starch in plants. Cocrystallization of
      Escherichia coli wild-type glycogen synthase (GS) with substrate ADPGlc and the
      glucan acceptor mimic HEPPSO produced a closed form of GS and suggests that
      domain-domain closure accompanies glycogen synthesis. Cocrystallization of the
      inactive GS mutant E377A with substrate ADPGlc and oligosaccharide results in the
      first oligosaccharide-bound glycogen synthase structure. Four bound
      oligosaccharides are observed, one in the interdomain cleft (G6a) and three on
      the N-terminal domain surface (G6b, G6c, and G6d). Extending from the center of
      the enzyme to the interdomain cleft opening, G6a mostly interacts with the highly
      conserved N-terminal domain residues lining the cleft of GS. The surface-bound
      oligosaccharides G6c and G6d have less interaction with enzyme and exhibit a more
      curled, helixlike structural arrangement. The observation that oligosaccharides
      bind only to the N-terminal domain of GS suggests that glycogen in vivo probably
      binds to only one side of the enzyme to ensure unencumbered interdomain movement,
      which is required for efficient, continuous glucan-chain synthesis.

PMID- 19761219
TI  - Calycinumines A and B, two novel alkaloids from Daphniphyllum calycinum.
AB  - Two novel alkaloids, calycinumines A (1) and B (2), were isolated from the twigs
      of Daphniphyllum calycinum. Calycinumine A (1) is the first example of C-22-nor
      yuzurimine-type alkaloids, and calycinumine B (2) features an unprecedented
      heteroatom-containing adamantane-like western hemisphere of the alkaloid. Their
      structures were elucidated by spectroscopic methods, and that of 1 was confirmed
      by a single-crystal X-ray diffraction.

PMID- 19761220
TI  - Characterization of lapis lazuli pigments using a multitechnique analytical
      approach: implications for identification and geological provenancing.
AB  - Many of the Raman spectra obtained from areas painted with ultramarine pigments
      in illuminated manuscript leaves from the 14th century Italian manuscript the
      Laudario of Sant'Agnese, in the collection of the J. Paul Getty Museum, also
      contain strong bands not typically associated with this pigment. The source of
      these features was investigated using a multitechnique analytical approach.
      Techniques employed include Raman microspectroscopy, scanning electron microscopy
      with energy-dispersive spectroscopy, electron probe microanalysis, and laser
      ablation inductively coupled plasma mass spectrometry. The results indicate the
      presence of diopside (CaMgSi(2)O(6)), a mineral commonly associated with lapis
      lazuli in nature, and suggest that transition metal dopants in the diopside may
      be responsible for the Raman features, likely the result of fluorescence with
      vibronic coupling. The implication of this result with respect to using Raman
      spectroscopy as a fast, noninvasive, and nondestructive method for determining
      the geological provenance of natural lapis lazuli pigments used in art is
      discussed.

PMID- 19761221
TI  - Automated ambient desorption-ionization platform for surface imaging integrated
      with a commercial Fourier transform ion cyclotron resonance mass spectrometer.
AB  - A fully automated atmospheric pressure ionization platform has been built and
      coupled with a commercial high-resolution Fourier transform ion cyclotron
      resonance mass spectrometer (FTICR-MS) instrument. The outstanding performance of
      this instrument allowed screening on the basis of exact masses in imaging mode.
      The main novel aspect was in the integration of the atmospheric pressure
      ionization imaging into the current software for matrix-assisted laser desorption
      ionization (MALDI) imaging, which allows the user of this commercial dual-source
      mass spectrometer to perform MALDI-MS and different ambient MS imaging from the
      same user interface and to utilize the same software tools. Desorption
      electrospray ionization (DESI) and desorption atmospheric pressure
      photoionization (DAPPI) were chosen to test the ambient surface imaging
      capabilities of this new ionization platform. Results of DESI imaging experiments
      performed on brain tissue sections are in agreement with previous MS imaging
      reports obtained by DESI imaging, but due to the high resolution and mass
      accuracy of the FTICR instrument it was possible to resolve several ions at the
      same nominal mass in the DESI-MS spectra of brain tissue. These isobaric
      interferences at low resolution are due to the overlap of ions from different
      lipid classes with different biological relevance. It was demonstrated that with
      the use of high-resolution MS fast imaging screening of lipids can be achieved
      without any preseparation steps. DAPPI, which is a relatively new and less
      developed ambient ionization technique compared to DESI, was used in imaging mode
      for the first time ever. It showed promise in imaging of phytocompounds from
      plant leaves, and selective ionization of a sterol lipid was achieved by DAPPI
      from a brain tissue sample.

PMID- 19761222
TI  - Locally enhanced sampling study of dioxygen diffusion pathways in
      homoprotocatechuate 2,3-dioxygenase.
AB  - Extradiol dioxygenases are characterized by activating dioxygen and incorporating
      both oxygen atoms into their substrates. Both experimental and theoretical
      investigations have been focused on the detection of intermediates in the
      reaction cycle in order to develop a general chemical mechanism of O(2)
      activation and insertion. However, little is known about the mechanism of how
      O(2) reaches the reaction sites of the related enzymes, which raises the question
      whether the rate of catalysis is limited by O(2) access to the active site. In
      this paper, two locally enhanced sampling molecular dynamics simulations were
      performed to determine the potential O(2) pathways inside a recently solved X-ray
      structure of homoprotocatechuate 2,3-dioxygenase. It is found that nominally
      identical subunits of the single homotetrameric structure contain distinct O(2)
      affinity diffusion pathways, which partly correlates with the observation of the
      simultaneous presence of three different reaction intermediates in four
      independent active sites. Residues that are critical for O(2) diffusion are also
      examined and discussed. In particular, we find that the breathing motion of the
      internal cavity defined by these residues results in O(2) migration process.

PMID- 19761224
TI  - Cascade synthesis of (E)-2-alkylidenecyclobutanols.
AB  - A facile, one-pot reaction cascade condenses 1,1,1-trichloroalkanes with
      alpha,beta-unsaturated ketones to unexpectedly furnish moderate to good yields of
      (E)-2-alkylidenecyclobutanols.

PMID- 19761223
TI  - Biophysical characterization of the iron in mitochondria from Atm1p-depleted
      Saccharomyces cerevisiae.
AB  - Atm1p is an ABC transporter localized in the mitochondrial inner membrane; it
      functions to export an unknown species into the cytosol and is involved in
      cellular iron metabolism. Depletion or deletion of Atm1p causes Fe accumulation
      in mitochondria and a defect in cytosolic Fe/S cluster assembly but reportedly
      not a defect in mitochondrial Fe/S cluster assembly. In this study the nature of
      the accumulated Fe was examined using Mossbauer spectroscopy, EPR, electronic
      absorption spectroscopy, X-ray absorption spectroscopy, and electron microscopy.
      The Fe that accumulated in aerobically grown cells was in the form of iron(III)
      phosphate nanoparticles similar to that which accumulates in yeast frataxin Yfh1p
      deleted or yeast ferredoxin Yah1p-depleted cells. Relative to WT mitochondria,
      Fe/S cluster and heme levels in Atm1p-depleted mitochondria from aerobic cells
      were significantly diminished. Atm1p depletion also caused a buildup of nonheme
      Fe(II) ions in the mitochondria and an increase in oxidative damage. Atm1p
      depleted mitochondria isolated from anaerobically grown cells exhibited WT levels
      of Fe/S clusters and hemes, and they did not hyperaccumulate Fe. Atm1p-depleted
      cells lacked Leu1p activity, regardless of whether they were grown aerobically or
      anaerobically. These results indicate that Atm1p does not participate in
      mitochondrial Fe/S cluster assembly and that the species exported by Atm1p is
      required for cytosolic Fe/S cluster assembly. The Fe/S cluster defect and the Fe
      accumulation phenotype, resulting from the depletion of Atm1p in aerobic cells
      (but not in anaerobic cells), may be secondary effects that are observed only
      when cells are exposed to oxygen during growth. Reactive oxygen species generated
      under these conditions might degrade iron-sulfur clusters and lower heme levels
      in the organelle.

PMID- 19761225
TI  - Liquid crystal phase transitions in systems of colloidal platelets with bimodal
      shape distribution.
AB  - We have studied a system of polydisperse, charged colloidal gibbsite platelets
      with a bimodal distribution in the particle aspect ratio. We observe a density
      inversion of the coexisting isotropic and nematic phases as well as a three-phase
      equilibrium involving a lower density nematic phase, an isotropic phase of
      intermediate density, and a higher density columnar phase. To relate these
      phenomena to the bimodality of the shape distribution, we have calculated the
      liquid crystal phase behavior of binary mixtures of thick and thin hard platelets
      for various thickness ratios. The predictions are based on the Onsager-Parsons
      theory for the isotropic-nematic (I-N) transition combined with a modified
      Lennard-Jones-Devonshire cell theory for the columnar (C) state. For sufficiently
      large thickness ratios, the phase diagram features an I-N density inversion and
      triphasic I-N-C equilibrium, in agreement with experiment. The density inversion
      can be attributed to a marked shape fractionation among the coexisting phases
      with the thick species accumulating in the isotropic phase. At high
      concentrations, the theory predicts a coexistence between two columnar phases
      with distinctly different concentrations. In experiment, however, the demixing
      transition is pre-empted by a transition to a kinetically arrested, glassy state
      with structural features resembling a columnar phase.

PMID- 19761226
TI  - Optimized use of a 50 microm internal diameter secondary column in a
      comprehensive two-dimensional gas chromatography system.
AB  - The focus of the present research is directed toward the development of a
      comprehensive two-dimensional gas chromatography (GC x GC) method, characterized
      by a greatly increased separation power, if compared with GC x GC approaches
      using classical column combinations. The analytical objective was achieved by
      using a 0.05 mm internal diameter (i.d.) capillary as second dimension, a split
      flow approach reported in previous research (Tranchida, P. Q., Casilli, A., Dugo,
      P., Dugo, G. and Mondello, L. Anal. Chem. 2007, 79, 2266-2275), and a twin-oven
      GC x GC instrument. The column combination employed was an orthogonal one: an
      apolar 30 m x 0.25 mm i.d. column was linked, by means of a Y-union, to a flame
      ionization detector (FID)-connected high-resolution 1 m x 0.05 mm i.d. polar one
      and to a 0.20 m x 0.05 mm i.d. uncoated capillary segment; the latter was
      connected to a manually operated split valve, located on top of the second GC. As
      previously shown, the generation of optimum gas linear velocities in both
      dimensions can be attained by splitting gas flows at the outlet of the first
      dimension (Tranchida, P. Q., Casilli, A., Dugo, P., Dugo, G. and Mondello, L.
      Anal. Chem. 2007, 79, 2266-2275). An optimized GC x GC method was developed and
      exploited for the analysis of a complex petrochemical sample. The satisfactory
      results attained were directly compared with those observed using the same
      instrumentation, equipped with what can be defined as a classical GC x GC split
      flow column set: the same primary column was connected to an FID-linked 1 m x
      0.10 mm i.d. polar one and to a 0.30 m x 0.10 mm i.d. uncoated capillary. It will
      be herein illustrated that there is still room for significant progress in the GC
      x GC field.

PMID- 19761227
TI  - Capacitive and solution resistance effects on voltammetric responses at a disk
      microelectrode covered with a self-assembled monolayer in the presence of
      electron hopping.
AB  - This article extends our previous works (Amatore, C.; Oleinick, A.; Svir, I.
      Anal. Chem. 2008, 80, 7947-7956; 7957-7963.) about the effects of resistive and
      capacitive distortions in voltammetry at disk microelectrodes. The particular
      case of voltammetry of a self-assembled monolayer carrying one redox site per
      molecule is investigated here. In addition, the effect of an uneven distribution
      of the effective electrochemical potential on the possibility of electron hopping
      (EH) contributions is examined. An original model of EH has been developed
      considering both diffusion-type (i.e., related to concentration gradients) and
      migration-type (i.e., imposed by an uneven distribution of the electrical
      potential due to an ohmic drop and capacitance charging) contributions. This
      predicts that as soon as the system performs out of thermodynamic equilibrium and
      provided that the EH rate constants are not too small the system tends to re
      establish its out-of-equilibrium state through EH. Hence, EH somewhat tries to
      compensate the voltammetric distortions that would be enforced by the uneven
      distribution of the electrochemical driving force incurred by the system due to
      an ohmic drop and capacitive charging. However, this rigorous analysis
      established that, though EH may be effective under specific circumstances
      particularly near the electrode edge, its overall influence on voltammetric waves
      remains negligible for any realistic experimental situation.

PMID- 19761228
TI  - A thermochromic thin film based on host-guest interactions in a layered double
      hydroxide.
AB  - Optically transparent thin films with thermochromic properties have been
      fabricated by means of cointercalation of different molar ratios of 4-(4
      anilinophenylazo)benzenesulfonate (AO5) and sodium dodecylbenzene sulfonate (SDS)
      into the galleries of a ZnAl layered double hydroxide (LDH). The X-ray
      diffraction (XRD) patterns of these thin films show that they are assembled in a
      highly c-oriented manner, and the basal spacing ranges from 2.95 to 2.63 nm with
      varying AO5/SDS molar ratio. The preferential orientation of AO5 in the galleries
      of 10% AO5-LDH (AO5/SDS = 10:90, molar percentage) was evaluated by the
      fluorescence polarization technique; the results show that AO5 anions are
      accommodated between sheets of ZnAl-LDH as monomeric units with a tilt angle Psi
      (defined as the angle between the transition dipole moment of the AO5 anion with
      respect to the normal to the LDH layer) of 74 degrees. It was found that the
      composite film exhibits marked thermochromic behavior (light yellow <==> reddish
      orange) in the temperature range of 35-65 degrees C, which is reversible over a
      number of heating-cooling cycles. It has been demonstrated that the thermochromic
      behavior results from tautomerism of interlayer AO5 and furthermore that both the
      host-guest and guest-guest interactions are key factors, since pristine AO5 shows
      no thermochromic performance. The 10% AO5-LDH film shows the highest
      thermochromic efficiency of all the films examined. Furthermore, a reversible
      contraction and expansion of the LDH basal spacing was also observed for this
      thin film over the same temperature range.

PMID- 19761229
TI  - Energetic and structural study of diphenylpyridine isomers.
AB  - The energetic and structural study of three diphenylpyridine isomers is presented
      in detail. The three isomers, 2,6-, 2,5-, and 3,5-diphenylpyridines, were
      synthesized via Suzuki-Miyaura methodology based on palladium catalysis, and the
      crystal structures of the isomers were obtained by X-ray diffraction. The
      relative energetic stabilities in the condensed and gaseous phases as well as
      volatilities and structures of the three studied isomers were evaluated,
      regarding the position of the phenyl groups relative to the nitrogen atom of the
      pyridine ring. The temperature, standard molar enthalpies, and entropies of
      fusion were measured and derived by differential scanning calorimetry. The vapor
      pressures of the considered isomers were determined by a static apparatus based
      on a MKS capacitance diaphragm manometer. The standard molar enthalpies,
      entropies, and Gibbs energies of sublimation, at T = 298.15 K, were derived, and
      the phase diagram near the triple point coordinates were determined for all
      isomers. The standard (p(o) = 0.1 MPa) molar enthalpies of combustion of all
      crystalline isomers were determined, at T = 298.15 K, by static bomb combustion
      calorimetry. The standard molar enthalpies of formation, in the crystalline and
      gaseous phases, at T = 298.15 K, were derived. The experimental results for the
      energetics in the gaseous phase of the three compounds were compared and assessed
      with the values obtained by ab initio calculations at different levels of theory
      (DFT and MP2) showing that, at this level of theory, the computational methods
      underestimate the energetic stability, in the gaseous phase, for these molecules.
      In order to understand the aromaticity in the central ring of each isomer,
      calculations of NICS (B3LYP/6-311G++(d,p) level of theory) values on the pyridine
      ring were also performed.

PMID- 19761230
TI  - Supramolecular complexation and enantiodifferentiating photocyclodimerization of
      2-anthracenecarboxylic acid with 4-aminoprolinol derivatives as chiral hydrogen
      bonding templates.
AB  - The photochirogenesis of 2-anthracenecarboxylic acid (AC) complexed to a hydrogen
      bonding template (TKS159) was investigated to obtain mechanistic information on
      how chirogenesis is achieved for the dimerization of AC. Complexation of AC to
      TKS159 leads to the shielding of one of the two surfaces of the prochiral AC
      molecule. The two diastereomeric AC-TKS complexes, i.e., re-AC-TKS and si-AC-TKS,
      were characterized by changes in the UV-vis, fluorescence, and circular dichroism
      spectra and excited-state lifetimes. The ee is not simply determined by the
      diastereomeric ratio of the re- and si-AC-TKS complexes but also depends on the
      relative lifetimes of the diastereomeric complexes. The relative population of
      the re and si complexes was calculated from the enantiomeric excess (ee) for the
      products, taking into account the relative lifetimes of the two complexes. These
      studies established a protocol that can be used to reveal the mechanism for
      photochirogenesis by investigating the ground state and the excited state
      behavior of supramolecular systems.

PMID- 19761231
TI  - Crossed-beam dynamics, low-temperature kinetics, and theoretical studies of the
      reaction S(1D) + C2H4.
AB  - The reaction between sulfur atoms in the first electronically excited state,
      S((1)D), and ethene (C(2)H(4)) has been investigated in a complementary fashion
      in (a) crossed-beam dynamic experiments with mass spectrometric detection and
      time-of-flight (TOF) analysis at two collision energies (37.0 and 45.0 kJ mol(
      1)), (b) low temperature kinetics experiments ranging from 298 K down to 23 K,
      and (c) electronic structure calculations of stationary points and product
      energetics on the C(2)H(4)S singlet and triplet potential energy surfaces. The
      rate coefficients for total loss of S((1)D) are found to be very large (ca. 4 x
      10(-10) cm(3) molecule(-1) s(-1)) down to very low temperatures indicating that
      the overall reaction is barrierless. From laboratory angular and TOF
      distributions at different product masses, three competing reaction channels
      leading to H + CH(2)CHS (thiovinoxy), H(2) + CH(2)CS (thioketene), and CH(3) +
      HCS (thioformyl) have been unambiguously identified and their dynamics
      characterized. Product branching ratios have also been estimated. Interpretation
      of the experimental results on the reaction kinetics and dynamics is assisted by
      high-level theoretical calculations on the C(2)H(4)S singlet potential energy
      surface. RRKM (Rice-Ramsperger-Kassel-Marcus) estimates of the product branching
      ratios using the newly developed singlet potential energy surface have also been
      performed and compared with the experimental determinations.

PMID- 19761232
TI  - Quantum-dot-modified electrode in combination with NADH-dependent dehydrogenase
      reactions for substrate analysis.
AB  - A quantum dot-electrode system was developed which allows the sensitive detection
      of NADH (nicotinamide adenine dinucleotide). The colloidal semiconductive
      CdSe/ZnS nanocrystals (quantum dots) are attached to gold by chemisorption via a
      dithiol compound. The current signal can be triggered by illumination of the
      quantum-dot-modified electrode surface. Because of photoexcitation, electron-hole
      pairs are generated in the quantum dots, which can be detected as anodic or
      cathodic photocurrent. The immobilization of the nanocrystals is verified by
      amperometric photocurrent and quartz crystal microbalance (QCM) measurements.
      This study shows that CdSe/ZnS quantum dot-modified electrodes allow
      concentration dependent NADH detection in the range of 20 microM to 2 mM already
      at rather low potentials (around 0 V vs. Ag/AgCl, 1 M KCl). Therefore such
      electrodes can be used in combination with NADH-producing enzyme reactions for
      the light-triggered analysis of the respective substrates of the biocatalyst. It
      can be shown that glucose detection is feasible with such an electrode system and
      photocurrent measurements.

PMID- 19761233
TI  - Investigation on Lewis acid mediated Diels-Alder reactions of 2-phosphono-2
      alkenoates. Application to total synthesis of (+/-)-alpha-alasken-8-one via
      reductive alkylation of resulting adduct.
AB  - The Lewis acid mediated Diels-Alder reactions of three 2-phosphono-2-alkenoates
      including triethyl 2-phosphonoacrylate (1), triethyl 2-phosphonobut-2-enoate (2),
      and ethyl 2-(diethoxyphosphono)-3-methylbut-2-enoate (3) have been investigated.
      Of several Lewis acids tested, tin(IV) chloride was shown to be the most
      effective at enhancing the regio- and stereoselectivity of the reactions of 1
      with the electron-rich dienes to result in the formation of the single regio-
      and/or stereoisomers in good yields. Bearing the beta methyl group(s), 2
      displayed much less reactivity than 1 while 3 was completely unreactive under the
      study's conditions. Throughout the investigation, we found that the
      cycloadditions of 2, especially of the Z-isomer, could be efficiently induced by
      using zinc chloride at elevated temperatures. Furthermore, a lithium
      naphthalenide (LN)-induced reductive alkylation process was applied to the
      resulting Diels-Alder adducts 4 to allow the phosphono group at the quaternary
      carbon centers to be replaced by various alkyl groups to afford the alkyl
      substituted esters 12, therefore practically turning 1 and 2 into the useful
      synthetic equivalents of the corresponding 2-alkyl 2-alkenoates that usually
      display poor Diels-Alder reactivity. Application of this combined operation has
      facilitated the total synthesis of the sesquiterpene natural product alpha
      alasken-8-one (8) in racemic form.

PMID- 19761234
TI  - Meroterpenes from Dichrostachys cinerea inhibit protein farnesyl transferase
      activity.
AB  - Eighteen new meroterpene derivatives, dichrostachines A-R (1-18), have been
      isolated from the root and stem barks of Dichrostachys cinerea, and their
      structures determined by spectroscopic means and molecular modeling. From a
      biosynthetic standpoint these compounds arise from a Diels-Alder reaction between
      a labdane diene of the raimonol type and a flavonoid B-ring-derived quinone. The
      hypothesis was tested by the partial synthesis of similar compounds by simply
      mixing methyl communate and a synthetic flavonoid quinone. The hemisynthetic
      compounds were shown by NMR to have configurations different from those of the
      natural products, thus allowing a refinement of the biosynthesis hypothesis. Most
      of the compounds were assayed for their ability to inhibit the enzyme protein
      farnesyl transferase. The most active compounds exhibited IC50 and cytotoxicity
      values in the 1 microM range.

PMID- 19761235
TI  - Switchable reactions of cyclopropanes with enol silyl ethers. Controllable
      synthesis of cyclopentanes and 1,6-dicarbonyl compounds.
AB  - Cu(SbF(6))(2)-catalyzed reaction of 2-substituted cyclopropane-1,1-dicarboxylates
      1 with enol silyl ethers 2 can be readily controlled: the reaction undergoes a
      cycloaddition to provide substituted cyclopentane derivatives 3 in excellent
      yields with high diastereoselectivities in the presence of complex 8/Cu(II);
      however, the same substrates afford acyclic 1,6-dicarbonyl products 4 via a
      cycloaddition-ring-opening reaction in up to 92% yield in the absence of ligand
      8. The mechanism for the ligand-switchable reactions was investigated by both
      control experiments and (1)H NMR studies. The substrate scope and limitation of
      the tunable transformation were also examined.

PMID- 19761236
TI  - Synthesis of monodisperse oligo(1,4-phenyleneethynylene-alt-1,4
      triptycyleneethynylene)s.
AB  - The synthesis of monodisperse oligo(p-phenyleneethynylene)s 8a(n) with
      alternating 2,5-dihexyl-1,4-phenylene and 6,14-di-tert-butyl-1,4-triptycylene
      units and orthogonally protected alkyne end groups is reported. Starting from
      6,14-di-tert-butyl-1-(2-triisopropylsilylethynyl)-4-(2
      trimethylsilylethynyl)triptycene (5a), 1,4-dihexyl-2,5-diiodobenzene (10), and
      1,4-dihexyl-2-iodo-5-(3-hydroxyprop-1-ynyl)benzene (9), oligomers with up to four
      repeating units, i.e., eight phenyleneethynylene units, were prepared through a
      partially divergent-convergent route with the alkynyl-aryl (Sonogashira-Hagihara)
      coupling as the key reaction. The starting compound 5a was prepared from
      triptycenequinone through a sequence of addition of 2
      trialkylsilylethynyllithium, reduction and concomitant elimination of water,
      conversion of the phenol into a triflate, and finally Pd/Cu-catalyzed coupling
      with trialkylsilylethyne. A similar access to the key compound for a stringent
      divergent-convergent route, 6,14-di-tert-butyl-1-(3-hydroxybut-1-ynyl)-4-(2
      triisopropylsilylethynyl)triptycene (6), is reported. The optical properties of
      the oligomers 8a(n) and the corresponding oligo(2,5-dihexyl-1,4
      phenyleneethynylene)s in dilute solution are almost identical, whereas they
      differ significantly for the solid, undiluted compounds.

PMID- 19761237
TI  - Tetrakis(thiadiazole)porphyrazines. 6. Spectroelectrochemical and density
      functional theory studies of the anions [TTDPzM](n-) (n = 1-4; M = Zn(II),
      Mg(II)(H(2)O), Cu(II), 2H(I)).
AB  - Following previous cyclic voltammetric studies of
      tetrakis(thiadiazole)porphyrazines [TTDPzM] where M = Zn(II), Mg(II)(H(2)O),
      Cu(II), or 2H(I) in nonaqueous media, a thin-layer spectroelectrochemical
      investigation was carried out in pyridine to characterize each stepwise one
      electron reduction of the electrogenerated [TTDPzM](n-) complexes where n = 1-4.
      A similar UV-visible spectrum was observed for each form of the anion,
      independent of the central metal ion and detailed theoretical calculations by
      density functional theory (DFT) and time-dependent DFT (TDDFT) methods were
      applied to interpret the spectral features of [TTDPzZn](n-) (n = 1-4) which was
      selected as representative for describing the ground and excited-state electronic
      structures of the entire [TTDPzM](n-) series. The use of two exchange-correlation
      functionals, the pure, asymptotically correct statistical average of orbital
      potentials (SAOP) and the hybrid B3LYP functionals, proved to be essential for
      attaining a correct assignment of the key spectral features. The nature and
      intensity of the main spectral features are highlighted and interpreted on the
      basis of the ground-state electronic structure of the complexes.

PMID- 19761238
TI  - Phage-induced alignment of membrane proteins enables the measurement and
      structural analysis of residual dipolar couplings with dipolar waves and lambda
      maps.
AB  - At pH > 6 added filamentous bacteriophage fd is compatible with many of the
      detergents used to solubilize membrane proteins for solution NMR studies of
      membrane proteins and, therefore, serves as an alignment media. In combination
      with strained polyacrylamide gel alignment, Dipolar Waves can be used to directly
      assess the secondary structure and a lambda-map extracts the order tensors for de
      novo structure calculation of membrane proteins without distance restraints.

PMID- 19761239
TI  - Resolution of planar chiral cationic (eta6-arene)tricarbonylmanganese complexes.
AB  - This contribution describes the first resolution of cationic (eta(6)
      arene)Mn(CO)(3) complexes through addition of d-(+)-camphor enolate,
      isomerization of the stereogenic center, and separation and recrystallization of
      the corresponding eta(5) diastereoisomers followed by rearomatization and
      elimination of the chiral auxiliary. This general unprecedented chiral
      nucleophile addition/elimination (eta(6)-eta(5))/(eta(5)-eta(6)) "round trip"
      sequence uses a cheap, commercially available chiral nucleophile. As it is
      compatible with the presence of halide and alkoxy groups, a huge number of
      applications are envisaged. Some of them, such as the synthesis of enantiopure
      substituted cyclohexenones, are reported in the present work.

PMID- 19761240
TI  - Mulberry leaf extract inhibits vascular smooth muscle cell migration involving a
      block of small GTPase and Akt/NF-kappaB signals.
AB  - Mulberry, the fruit of Morus alba, is commonly used in Chinese medicines because
      of its many pharmacologic effects. Mulberry leaves contain many phenolic
      antioxidants that can reduce cardiovascular disease. Atherosclerosis involves
      proliferation and migration of vascular smooth muscle cell (VSMC). Thus, we
      investigated the mechanisms by which mulberry leaf extract (MLE) might inhibit
      migration of VSMC. MLE was rich in polyphenols (44.82%), including gallic acid,
      protocatechuic acid, catechin, gallocatechin gallate, caffeic acid, epicatechin,
      rutin, and quercetin. MLE could inhibit the migration of A7r5 cells in a dose-
      and time-dependent manner. MLE also inhibited the activities of matrix
      metalloproteinases (MMPs) MMP-2 and MMP-9, protein expressions, and
      phosphorylation of FAK and Akt, and protein expressions of small guanosine
      triphosphatases (GTPases: c-Raf, Ras, Rac1, Cdc42, and RhoA) in a dose-dependent
      manner. NF-kappaB expression was also inhibited by MLE. MLE could effectively
      inhibit the migration of VSMC by blocking small GTPase and Akt/NF-kappaB signals.

PMID- 19761241
TI  - Application of the Olfactoscan method to study the ability of saturated aldehydes
      in masking the odor of methional.
AB  - A novel technology (Olfactoscan screening) was applied to screen for volatiles
      including saturated aldehydes that mask the perception of methional, an off
      flavor commonly found in orange juice. For the screening experiment, methional
      odor pulses were generated by an olfactometer and, one by one, mixed with
      alternating odor compounds that were separated by gas chromatography from a model
      solution. Trained panelists evaluated the odor mixtures so formed for methional
      intensity. Methional perception was significantly suppressed if it was mixed with
      octanal (p < 0.05). Similar interactions were not observed between methional and
      other volatiles including hexanal. This observation suggests highly specific
      interaction between methional and octanal. Octanal-methional interactions were
      then tested in orange juice (quantitative descriptive analysis with expert panel,
      n = 10). At certain levels, octanal significantly suppressed methional-associated
      off-notes such as "musty", "decayed orange", and "potato" (p < 0.01). The overall
      flavor quality of the orange juice was significantly improved (p < 0.01). As it
      occurs naturally in orange juice, an enrichment of octanal during juice
      production is suggested to prevent a methional-induced loss of orange flavor
      quality.

PMID- 19761243
TI  - Semiconstant-time P,H-COSY NMR: analysis of complex mixtures of phospholipids
      originating from Helicobacter pylori.
AB  - Lipids play a central role in numerous biological events, ranging from normal
      physiological processes to host-pathogen interactions. The proposed semiconstant
      time (31)P,(1)H-COSY NMR experiment provides identification of known and
      structural characterization of unknown phospholipids in complex membrane extracts
      with high sensitivity, based on the combination of their (1)H and (31)P chemical
      shifts and coupling patterns. Furthermore, the spectra allow quantification of
      phospholipid composition. Analysis of the phospholipid composition of
      Helicobacter pylori, the causative agent of peptic ulcer disease, showed the
      presence of uncommon phospholipids. This novel NMR approach allows the study of
      changes in membrane composition in response to biological stimuli and opens up
      the possibility of identifying soluble phosphorus species in a number of research
      fields.

PMID- 19761244
TI  - A combined crystallographic and molecular dynamics study of cathepsin L
      retrobinding inhibitors.
AB  - We report the crystal structures of three noncovalent retrobinding inhibitors in
      complex with mature cathepsin L up to resolutions of 2.5, 1.8, and 2.5 A,
      respectively. These inhibitors were Bpa-(Nepsilon-Bpa)Lys-DArg-Tyr-Npe, Bpa
      (Nepsilon-Bpa)Lys-DArg-Phe-Npe, and Bpa-MCys-DArg-Phe-Npe, where Bpa =
      biphenylacetyl and Pea = N-phenylethyl. These were selected to clarify the
      binding mode of the biphenyl groups in the S' subsites because the addition of a
      second biphenyl does not improve potency. Examination of the symmetry-related
      monomers in the crystal structures revealed inhibitor-inhibitor crystal packing
      interactions. Molecular dynamics simulations were then used to explore the
      structure and dynamical behavior of the isolated protein-ligand complexes in
      solution. In the simulations, the backbone biphenyl groups for all three
      inhibitors ended up in the same location despite having started out in different
      orientations in the initial crystal structure conformations. The lack of improved
      potency of the larger inhibitors over the smaller one is attributed to a
      correspondingly greater entropic cost of binding.

PMID- 19761245
TI  - Effect of molecular orientation on mechanical property of single electrospun
      fiber of poly[(R)-3-hydroxybutyrate-co-(R)-3-hydroxyvalerate].
AB  - Electrospun poly[(R)-3-hydroxybutyrate-co-(R)-3-hydroxyvalerate] (PHBV) fibers
      were collected by using a counter electrode collector or a rotating disk
      collector. The molecular orientation and mechanical property of single PHBV fiber
      were studied. 2-D wide-angle X-ray diffraction and polarized Fourier transform
      infrared spectra of the macroscopically aligned fibers confirmed the orientation
      of polymer chains, with PHBV chains preferentially oriented along the fiber axis.
      The degree of orientation increased with increasing fiber take-up velocity. X-ray
      diffraction pattern also indicates the development of beta-form crystal in
      electrospun PHBV fibers collected at an angular velocity of 1500 rpm. The thermal
      behavior of electrospun PHBV fibers was studied using modulated differential
      scanning calorimetry. The tensile properties of single electrospun PHBV fibers
      were studied using a nanotensile tester. Our results indicate that electrospun
      PHBV fiber with a higher degree of molecular orientation exhibits a higher
      tensile modulus and strength but lower strain at break.

PMID- 19761247
TI  - A Glyco-mix of Approaches To Studying Carbohydrates.

PMID- 19761251
TI  - Ralph f. Hirschmann, 1922-2009. A perspective.

PMID- 19761252
TI  - Fluorescent glycan derivatives: their use for natural glycan microarrays.
AB  - Glycan microarrays have become powerful tools in the investigation of biological
      systems because they enable fast, quantitative, and simultaneous analysis of
      glycan-protein interactions with small quantities of samples. One hurdle in the
      construction of glycan microarrays is to obtain a diverse set of glycans for
      immobilization on surfaces. An article in this issue of ACS Chemical Biology
      describes the microscale preparation of fluorescently labeled reactive glycans in
      a cyclic form of the reducing sugar, from natural sources, that can be utilized
      directly to create natural glycan microarrays for use in functional glycomics.

PMID- 19761253
TI  - Mass spectrometric analysis of a cyclic 7,8-butanoguanine adduct of N
      nitrosopyrrolidine: comparison to other N-nitrosopyrrolidine adducts in rat
      hepatic DNA.
AB  - The well established rat hepatocarcinogen N-nitrosopyrrolidine (NPYR, 1) requires
      metabolic activation to DNA adducts to express its carcinogenic activity. Among
      the NPYR-DNA adducts that have been identified, the cyclic 7,8-butanoguanine
      adduct 2-amino-6,7,8,9-tetrahydro-9-hydroxypyrido[2,1-f]purine-4(3H)-one (6) has
      been quantified using moderately sensitive methods, but its levels have never
      been compared to those of other DNA adducts of NPYR in rat hepatic DNA.
      Therefore, in this study, we developed a sensitive new LC-ESI-MS/MS-SRM method
      for the quantitation of adduct 6 and compared its levels to those of several
      other NPYR-DNA adducts formed by different mechanisms. The new method was shown
      to be accurate and precise, with good recoveries and low fmol detection limits.
      Rats were treated with NPYR by gavage at doses of 46, 92, or 184 mg/kg body
      weight and sacrificed 16 h later. Hepatic DNA was isolated and analyzed for NPYR
      DNA adducts. Adduct 6 was by far the most prevalent, with levels ranging from
      about 900-3000 micromol/mol Gua and responsive to dose. Levels of adducts formed
      from crotonaldehyde, a metabolite of NPYR, were about 0.2-0.9 micromol/mol dGuo,
      while those of adducts resulting from reaction with DNA of tetrahydrofuranyl-like
      intermediates were in the range of 0.01-4 micromol/mol deoxyribonucleoside. The
      results of this study demonstrate that, among typical NPYR-DNA adducts, adduct 6
      is easily the most abundant in hepatic DNA. Since previous studies have shown
      that it can be detected in the urine of NPYR-treated rats, the results suggest
      that it is a potential candidate as a biomarker for assessing human exposure to
      and metabolic activation of NPYR.

PMID- 19761254
TI  - Structural interpretation of activity cliffs revealed by systematic analysis of
      structure-activity relationships in analog series.
AB  - Discontinuity in structure-activity relationships (SARs) is caused by so-called
      activity cliffs and represents one of the major caveats in SAR modeling and lead
      optimization. At activity cliffs, small structural modifications of compounds
      lead to substantial differences in potency that are essentially unpredictable
      using quantitative structure-activity relationship (QSAR) methods. In order to
      better understand SAR discontinuity at the molecular level of detail, we have
      analyzed different compound series in combinatorial analog graphs and determined
      substitution patterns that introduce activity cliffs of varying magnitude. So
      identified SAR determinants were then analyzed on the basis of complex crystal
      structures to enable a structural interpretation of SAR discontinuity and
      underlying activity cliffs. In some instances, SAR discontinuity detected within
      analog series could be well rationalized on the basis of structural data, whereas
      in others a structural explanation was not possible. This reflects the intrinsic
      complexity of small molecule SARs and suggests that the analysis of short-range
      receptor-ligand interactions seen in X-ray structures is insufficient to
      comprehensively account for SAR discontinuity. However, in other cases, SAR
      information extracted from ligands was incomplete but could be deduced taking X
      ray data into account. Thus, taken together, these findings illustrate the
      complementarity of ligand-based SAR analysis and structural information.

PMID- 19761255
TI  - Scaling the structure factors of protein limit colloid-polymer mixtures.
AB  - The scaling of the phase boundaries and structure factors of protein limit
      colloid-polymer mixtures has been investigated through the addition of large
      nonadsorbing polymer chains to a solution of small microemulsion droplets. The
      colloid-polymer size ratio has been varied between 10 and 16 by changing the
      microemulsion droplet size; the phase boundaries were shown previously to observe
      theoretical scaling relations very well [Langmuir 2009, 25 (7), 3944-3952]. These
      thermodynamic scaling relations are now shown to also hold extremely well for the
      individual and cross-term partial structure factors. The structure factors for
      systems with different size ratios occupying the same point in scaled phase space
      show extremely good agreement. The properties and stability of these mixtures are
      governed by the polymer mesh.

PMID- 19761256
TI  - Covalently bonded layer-by-layer assembly of multifunctional thin films based on
      activated esters.
AB  - We demonstrate that chemically stable, multifunctional polymer thin films can be
      obtained using the layer-by-layer (LbL) deposition based on covalent bonds
      between adsorbing chains. Poly(pentafluorophenyl-4-vinylbenzoate) (P1) or
      poly(pentafluorophenylacrylate) (P2) polymers were assembled with poly(allyl
      amine) (PAAm) to yield LbL multilayer films through amide bond formation by the
      reaction between activated esters of P1 or P2 and amine groups in PAAm, which was
      quantitatively monitored by Fourier transform infrared spectroscopy (FT-IR). It
      was found that the difference in the solubility of P1 and P2 against ethanol,
      which was used as the solvent for PAAm, during the LbL deposition yields
      different reaction conversion for the activated esters in either P1 or P2: the
      reaction conversion of P2 is higher than the conversion with P1. In addition,
      free (or unreacted) activated esters and amine groups remaining in the PAAm/P1
      LbL film were further utilized for the incorporation of multiple functional
      materials (5-((2-aminoethyl)amino)naphthalene-1-sulfonic acid (EDANS) and
      Rhodamine B dyes in the present case) by post-treatments in order to further
      tailor the film properties. It was also demonstrated that the surface functional
      groups (activated esters) in the LbL films can also be utilized for surface
      patterning with one functional material, followed by functionalization with a
      second functional material during the post-treatment throughout the whole film.
      Finally, the PAAm/P1 and PAAm/P2 LbL films were shown to be quite stable in the
      extreme pH range, and free-standing films can easily be obtained by the treatment
      of the films with mild acidic conditions. The versatility of incorporating
      multiple functional materials into a single multilayer film as well as the
      excellent physicochemical stability of the covalently bonded multilayer free
      standing films proves to be quite useful to design flexible and multifunctional
      thin film structures for many chemical and biological applications.

PMID- 19761257
TI  - Structure of a switchable subtilisin complexed with a substrate and with the
      activator azide.
AB  - An engineered variant of the protease subtilisin from Bacillus amyloliquefaciens,
      in which the D32A mutation renders the enzyme's activity dependent on the
      presence of certain small anions such as fluoride or azide, has been produced.
      This modified enzyme has applications as an azide or fluoride-triggered
      expression-purification tool. We report activity measurements showing that the
      enzyme is activated more than 3000-fold by azide and describe the 1.8 A
      resolution structure of an inactive form (by replacing the catalytic nucleophile
      Ser 221 with alanine) of the protease, in complex with azide and with a substrate
      that spans the active site. Both enzyme and substrate have been engineered to
      increase their stability and the affinity of their interaction. The substrate is
      based on a stabilized subtilisin prodomain, extended across the active site by
      the addition of four residues at its C-terminus. In the crystal structure, the
      substrate is well-ordered across the active site, and the azide anion is observed
      bound adjacent to Ala 32. The structures of the substrate complex in three
      different crystals (anion-free, fluoride-soaked, and azide-soaked) are compared.
      These structures provide extensive information for understanding subtilisin's
      substrate binding and catalytic mechanism, and for the development of
      biotechnology tools based on anion-activated proteolysis. The mechanism of anion
      dependent proteolysis appears to be a slight modification of the accepted charge
      relay mechanism for serine proteases.

PMID- 19761258
TI  - One-pot preparation of hollow silica spheres by using thermosensitive poly(N
      isopropylacrylamide) as a reversible template.
AB  - Hollow silica nanospheres with mesoporous shells were successfully fabricated
      with a new one-pot strategy by using a thermosensitive polymer, poly(N
      isopropylacrylamide) (PNIPAm), as a reversible template without the need of
      further calcination or chemical etching. By simply regulating the solution
      temperature with respect to the lower critical solution temperature (LCST) of
      PNIPAm, PNIPAm chains can reversibly form aggregates or dissolve in aqueous
      solution. The thermosensitive character makes PNIPAm chains behave as soft
      templates for the formation of core-shell silica nanospheres at elevated
      temperature (>LCST), and they will then diffuse out of the cores at lower
      temperature (<LCST), leading to the formation of hollow silica nanospheres. The
      TEM, SEM, XRD, and N(2) adsorption-desorption results indicate that the shells of
      such hollow silica nanospheres also contain large quantities of irregular
      mesopores. This new strategy was also tested with another thermosensitive
      polymer, poly(vinyl methyl ether) (PVME). However, only solid silica nanospheres
      with a broad size distribution were obtained when PVME was used. We speculated on
      the possible formation mechanism of hollow silica nanospheres with PNIPAm
      templates. The effects of the initial concentration of PNIPAm, the molecular
      weight of PNIPAm, and the pretreatment of silica precursor on the morphology and
      size of the resultant hollow silica nanospheres were also investigated. The
      PNIPAm soft templates were confirmed to be recyclable.

PMID- 19761259
TI  - Correctors enhance maturation of DeltaF508 CFTR by promoting interactions between
      the two halves of the molecule.
AB  - Deletion of Phe508 in cystic fibrosis transmembrane conductance regulator
      (DeltaF508 CFTR) causes cystic fibrosis. CFTR consists of two homologous halves
      with each containing a nucleotide-binding domain (NBD) and a transmembrane domain
      (TMD). DeltaF508 CFTR appears to be trapped in an incompletely folded state.
      Small molecules (correctors) promote folding of DeltaF508 CFTR with relatively
      low efficiency. Understanding the mechanism of repair may lead to the development
      of more effective correctors. Here we tested the effect of correctors and the
      DeltaF508 mutation on interactions between the halves of CFTR when expressed as
      separate polypeptides. Glycosylation of C-half CFTR was defective when expressed
      alone as a mixture of core and unglycosylated proteins was detected. Coexpression
      of C-half CFTR with either wild-type N-half or DeltaF508/N-half CFTR, however,
      increased the amount of core-glycosylated protein, but only coexpression with
      wild-type N-half promoted maturation of C-half CFTR (Endo H resistant). This
      suggested that the DeltaF508 mutation inhibited some interactions between N-half
      and C-half CFTRs. Interaction of A52-tagged wild-type N-half or DeltaF508/N-half
      CFTR with histidine-tagged C-half CFTR was then followed by nickel-chelate
      chromatography. Coexpression of A52-tagged wild-type N-half or DeltaF508/N-half
      CFTR with histidine-tagged C-half CFTR resulted in the wild-type N-half CFTR but
      not DeltaF508/N-half CFTR protein being retained on the column. Coexpression of
      DeltaF508/N-half and C-half CFTR in the presence correctors VX-325 and corr-4a,
      however, restored interactions between the two halves. An interaction that was
      restored was that between NBD1 and TMD2 as the correctors restored cross-linking
      of mutant DeltaF508/NBD1(V510C)/TMD2(A1067C). Therefore, correctors promote
      proper interactions between the two halves of CFTR.

PMID- 19761260
TI  - Superhydrophobic aluminum surfaces by deposition of micelles of fluorinated block
      copolymers.
AB  - Superhydrophobic surfaces are generated by chemisorption on aluminum substrates
      of fluorinated block copolymers synthesized by reversible addition-fragmentation
      chain transfer in supercritical carbon dioxide. In an appropriate solvent, those
      block copolymers can form micelles with a fluorinated corona, which are grafted
      on the aluminum substrate thanks to the presence of carboxylic acid groups in the
      corona. Water contact angle and drop impact analysis were used to characterize
      the wettability of the films at the macroscale, and atomic force microscopy
      measurements provided morphological information at the micro- and nanoscale. The
      simple solvent casting of the polymer solution on a hydroxylated aluminum surface
      results in a coating with multiscale roughness, which is fully superhydrophobic
      over areas up to 4 cm(2).

PMID- 19761261
TI  - Structural basis of the hydride transfer mechanism in F(420)-dependent
      methylenetetrahydromethanopterin dehydrogenase.
AB  - F(420)-dependent methylenetetrahydromethanopterin (methylene-H(4)MPT)
      dehydrogenase (Mtd) of Methanopyrus kandleri is an enzyme of the methanogenic
      energy metabolism that catalyzes the reversible hydride transfer between methenyl
      H(4)MPT(+) and methylene-H(4)MPT using coenzyme F(420) as hydride carrier. We
      determined the structures of the Mtd-methylene-H(4)MPT, Mtd-methenyl-H(4)MPT(+),
      and the Mtd-methenyl-H(4)MPT(+)-F(420)H(2) complexes at 2.1, 2.0, and 1.8 A
      resolution, respectively. The pterin-imidazolidine-phenyl ring system is present
      in a new extended but not planar conformation which is virtually identical in
      methenyl-H(4)MPT(+) and methylene-H(4)MPT at the current resolution. Both
      substrates methenyl-H(4)MPT(+) and F(420)H(2) bind in a face to face arrangement
      to an active site cleft, thereby ensuring a direct hydride transfer between their
      C14a and C5 atoms, respectively. The polypeptide scaffold does not reveal any
      significant conformational change upon binding of the bulky substrates but in
      turn changes the conformations of the substrate rings either to avoid clashes
      between certain ring atoms or to adjust the rings involved in hydride transfer
      for providing an optimal catalytic efficiency.

PMID- 19761262
TI  - Effects of poly(L-lysine) substrates on attached Escherichia coli bacteria.
AB  - Poly(L-lysine) (PLL) is a cationic polymer that is often used for attaching and
      immobilizing cells to glass substrates for further investigation by, e.g., AFM
      techniques. Because of their small size, bacterial attachment is most easily done
      using thick air-dried PLL coatings--though thinner PLL coatings are also used and
      are commercially available. Nevertheless, the antimicrobial activity of PLL is
      well-established. Accordingly, we have investigated the physiological effects of
      suspended PLL and of PLL coatings on individual Escherichia coli bacteria through
      the pole-to-pole oscillations of cytoplasmic MinD-GFP fusion proteins. For
      planktonic bacteria, suspended PLL concentrations at the micromolar level
      quenched MinD-GFP oscillations and inhibited bacterial growth. On coverslips with
      PLL coatings prepared by short exposures of the slides to PLL solutions, followed
      by rinsing, only a fraction of available bacteria attached after hours of
      settling time. Min oscillations in the attached bacteria, however, were strong
      and only moderately slowed. On thick PLL coatings, prepared by drying drops on
      the slides followed by a brief rinse with deionized water, cells attached well
      within 15 min. With thick coatings, average oscillation periods for bacteria
      increased significantly, and considerable cell-to-cell variability was also
      observed; subsequent replacement of buffer with distilled water led to much
      larger period increases and/or fading of fluorescence intensity. We demonstrate
      that Min oscillations are a useful metric for bacteria attached to adhesion
      layers. We suggest that thick PLL coatings should probably be avoided for
      bacterial attachment, and that even thin PLL coatings can have significant
      effects on bacterial physiology.

PMID- 19761263
TI  - Criterion for reversal of thermal Marangoni flow in drying drops.
AB  - The thermal Marangoni flow induced by nonuniform surface temperature has been
      widely invoked to interpret the deposition pattern from drying drops. The surface
      temperature distribution of a drying droplet, although being crucial to the
      Marangoni flow, is still controversial. In this paper, the surface temperature in
      the drop central region is analyzed theoretically based on an asymptotic analysis
      on the heat transfer in such region, and a quantitative criterion is established
      for the direction of the surface temperature gradient and the direction of the
      induced Marangoni flow of drying drops. The asymptotic analysis indicates that
      these two directions will reverse at a critical contact angle, which depends not
      only on the relative thermal conductivities of the substrate and liquid, but also
      on the ratio of the substrate thickness to the contact-line radius of the
      droplet. The theory is corroborated experimentally and numerically, and may
      provide a potential means to control deposition patterns from drying droplets.

PMID- 19761264
TI  - o-Fluoranil: stereochemistry and mechanism of its Diels-Alder reactions.
AB  - In the absence of significant steric effects, Diels-Alder reactions of the title
      quinone generally take place with preservation of configuration, and are
      therefore probably concerted. However, hybrid density functional calculations
      indicate that often these reactions are highly asynchronous. Steric hindrance can
      result in reaction at quinone oxygen instead of carbon. Preference for endo over
      exo cycloaddition is observed, and is reinforced by a repulsive secondary orbital
      interaction in exo transition states.

PMID- 19761265
TI  - Facile synthesis of hierarchically mesoporous silica particles with controllable
      cavity in their surfaces.
AB  - Novel and uniform mesoporous silica particles with controllable cavities in their
      surface have been fabricated using PAA and CTAB as dual templates in a mild
      reaction system. Herein, a series of hierarchically distinct silica particles can
      be obtained by simply adjusting the mass ratios (R) of PAA to CTAB. When the R
      value continues to decrease, the corresponding number and opening size of these
      cavities are also increased. However, if no PAA added, only unique monodisperse
      mesoporous silica spheres with uniform size of approximately 400 nm can be
      obtained. These specific silica particles were characterized by means of small
      angle X-ray diffraction (XRD), scanning electron microscope (SEM), transmission
      electron microscope (TEM), Fourier-transform infrared (FT-IR) spectra, and
      nitrogen adsorption-desorption measurements. Results show that these unique
      mesoporous silica particles totally behave as an hexagonally ordered mesophase.
      The maximum BET surface area can be as high as 891 m(2)/g, and the maximum pore
      volumes can be as large as 0.27 cm(3)/g. Notably, the specific cavity features
      including opening size and cavity number almost do not change after calcination
      treatment. Moreover, a possible formation mechanism of the hierarchically
      distinct silica particles has been put forward, considering that the specific
      interface instability effect, the reduction in the surface free energy, and the
      synergic self-assembly of PAA and CTAB in solution can play a key role in
      mediating the formation of the hierarchical silica nanostructures. In general,
      the synthesis route is simple and straightforward for the preparation of the
      other biomineral nanostructures and may play an important role in
      microencapsulation.

PMID- 19761266
TI  - Palladium-catalyzed preparation of silyl enolates from alpha,beta-unsaturated
      ketones or cyclopropyl ketones with hydrosilanes.
AB  - Alpha,beta-unsaturated ketones and cyclopropyl ketones undergo palladium
      catalyzed hydrosilylation with hydrosilanes to yield (Z)-silyl enolates.

PMID- 19761267
TI  - Transport of neutral and ionic solutes: the gel/electrode and gel/electrolyte
      interfaces.
AB  - Transport through a polysaccharide gel phase has been investigated
      voltammetrically using both redox voltammetry at a gel covered electrode and ion
      transfer voltammetry across the gel/liquid interface (Gel/L). The apparent
      diffusion coefficients, D(app), of a range of neutral and ionic electroactive
      species have been determined in both uncharged and anionic polysaccharide media,
      agar, and kappa-carrageenan, respectively. It is shown that the diffusion of
      electroactive species in agar gel occurs at a rate similar to that of diffusion
      in aqueous solution for a range of redox couples. In the kappa-carrageenan
      medium, by contrast, the diffusion coefficient obtained for cationic solutes was
      found to be approximately an order of magnitude lower than the value in aqueous
      solution. The difference in D(app) is attributed to two independent processes:
      electrostatic interactions between the charge of the sulfonate groups of the
      kappa-carrageenan gel and the charge of the solute, as well a change in hydration
      of the solute molecules.

PMID- 19761268
TI  - Flexible strategy for immobilizing redox-active compounds using in situ
      generation of diazonium salts. Investigations of the blocking and catalytic
      properties of the layers.
AB  - A versatile two-step method is developed to covalently immobilize redox-active
      molecules onto carbon surfaces. First, a robust anchoring platform is grafted
      onto surfaces by electrochemical reduction of aryl diazonium salts in situ
      generated. Depending on the nature of the layer termini, -COOH or -NH(2), a
      further chemical coupling involving ferrocenemethylamine or ferrocene carboxylic
      acid derivatives leads to the covalent binding of ferrocene centers. The chemical
      strategy using acyl chloride activation is efficient and flexible, since it can
      be applied either to surface-reactive end groups or to reactive species in
      solution. Cyclic voltammetry analyses point to the covalent binding of ferrocene
      units restricted to the upper layers of the underlying aryl films, while AFM
      measurements show a lost of compactness of the layers after the chemical
      attachment of ferrocene centers. The preparation conditions of the anchoring
      layers were found to determine the interfacial properties of the resulted
      ferrocenyl-modified electrodes. The ferrocene units promoted effective redox
      mediation providing that the free redox probes are adequately chosen (i.e., vs
      size/formal potential) and the underlying layers exhibit strong blocking
      properties. For anchoring films with weaker blocking effect, the coexistence of
      two distinct phenomena, redox mediation and ET at pinholes could be evidenced.

PMID- 19761269
TI  - Synthesis of fullerene-fused lactones and fullerenyl esters: radical reaction of
      [60]fullerene with carboxylic acids promoted by manganese(III) acetate and
      lead(IV) acetate.
AB  - The manganese(III) acetate-mediated radical reaction of [60]fullerene with
      carboxylic acids in the presence of 4-(dimethylamino)pyridine exclusively
      afforded the [60]fullerene-fused lactones. Interestingly, the lead(IV) acetate
      promoted radical reaction of [60]fullerene with the same carboxylic acids
      selectively gave another type of fullerene products, i.e., fullerenyl esters.
      Possible mechanisms for the formation of fullerene products are proposed.

PMID- 19761270
TI  - Dynamics of partially oriented L-phenylalanine-d(8) in the CsPFO/H(2)O lyotropic
      system via (2)H NMR relaxation studies.
AB  - Dynamics of the l-phenylalanine-d(8) has been here investigated by analyzing the
      (2)H NMR spin-lattice relaxation times of this selectively deuterium enriched
      amino acid diluted in the cesium pentadecafluorooctanoate/water (CsPFO/H(2)O)
      lyotropic system both in the nematic (N(+)(D)) and in the lamellar (L(D)) phases.
      Information on the internal and overall molecular motions as well as on
      collective motions has been achieved by a global fitting procedure. The dynamic
      processes affecting this probe molecule reflect its particular conformational and
      interaction properties with respect to the lyotropic environment. The best
      reproduction of the experimental data is obtained by assuming free internal
      reorientations of the benzylic moiety, which results in diffusion constants of
      the same order of magnitude of the overall molecular spinning motion. Moreover,
      the contribution of collective motions (order director fluctuations and layer
      undulations) is estimated to be greater than that commonly observed by other
      techniques in lyotropic systems.

PMID- 19761271
TI  - One-pot synthesis of lactams using domino reactions: combination of Schmidt
      reaction with Sakurai and aldol reactions.
AB  - A series of domino reactions in which the intramolecular Schmidt reaction is
      combined with either a Sakurai reaction, an aldol reaction, or both is reported.
      The Sakurai reaction of an allylsilane with an azido-containing enone under Lewis
      acidic conditions followed by protonation of the resulting titanium enolate
      species allowed for a subsequent intramolecular Schmidt reaction. Alternatively,
      the intermediate titanium enolate could undergo an aldol reaction followed by the
      intramolecular Schmidt reaction to form lactam products with multiple stereogenic
      centers. The stereochemical features of the titanium enolate aldol reaction with
      several 3-azidoaldehyde substrates during this domino process is discussed.

PMID- 19761272
TI  - Quantum stereodynamics for the two product channels of the F + HD reaction from
      the complete scattering matrix in the stereodirected representation.
AB  - For the two exit arrangements of the F + HD reaction, the full scattering matrix
      is obtained by exact quantum dynamics on an accurate potential energy surface.
      The S matrix is expressed in the stereodirected representation, for the first
      time, for all channels of a triatomic reaction. We analyze a collision energy
      where the dominant reaction mechanism is direct and a total angular momentum J =
      0. It is found that the introduction of steric quantum numbers (correlated in the
      vector model to the angles measuring directions of approaching reactants and of
      separating products) provides a sharp description of stereodynamical features for
      both exit channels.

PMID- 19761273
TI  - On the spectral behavior of an ionic styryl dye: effect of micelle-polyethylene
      block-polyethylene glycol diblock copolymer assembly.
AB  - The interaction of anionic micelle sodium dodecyl sulfate (SDS) and amphiphilic
      block copolymers polyethylene-b-polyethylene glycol (PE-b-PEG) and the sharp
      change of excited-state charge-transfer complex photophysics of 2-(4
      (dimethylamino)styryl)-1-methylpyridinium iodide (DASPMI) inside of the
      supramolecular assembly have been addressed in the paper. The dramatic
      enhancement of emission intensity of DASPMI incorporated inside of the
      nanostructure formed by micellar and polymeric chains indicates a completely
      different environment compared to that in the water and micellar system. A huge
      increase in the rotational relaxation time obtained from time-resolved anisotropy
      decay and the value of the order parameter is indicative of a very restrictive
      regime in the self-assembly system. The wobbling and translational motion of the
      probe is also restricted inside of the micelle-polymer aggregate due to the
      presence of polymer chains. The translational diffusion coefficient is
      drastically reduced due to the aggregation.

PMID- 19761274
TI  - Vulvar lichen sclerosus in the elderly: pathophysiology and treatment update.
AB  - Lichen sclerosus is a chronic skin condition that most commonly affects the
      anogenital skin of postmenopausal women. The aetiology of the condition is
      multifactorial. The most common presenting symptom is itching. Lichen sclerosus
      has a characteristic appearance. Diagnosis is made with vulvar biopsy. Treatment
      is important and the regimen most often includes topical corticosteroid
      ointments. Lifetime surveillance of the skin is imperative because of the
      increased risk of squamous cell carcinoma in patients with lichen sclerosus.

PMID- 19761276
TI  - Novel therapies for pemphigus vulgaris: an overview.
AB  - Pemphigus comprises a group of autoimmune, mucocutaneous blistering disorders.
      Its principal cause may be a group of antibodies directed against proteins
      present on the surface of keratinocytes that provide mechanical structure to the
      epidermis. In the case of pemphigus vulgaris, the characteristic blistering noted
      just above the basal layer may be triggered by autoantibodies directed against
      desmoglein 3 (Dsg3). The process by which the binding of these antibodies leads
      to acantholysis, apoptosis and eventual loss of epidermal function is not
      completely understood. Current therapies are primarily directed against the
      formation of these antibodies by suppression of the immune system, and are
      associated with significant adverse events. As our understanding of the
      pathophysiology of pemphigus increases, newer therapies have been proposed and
      evaluated. These novel therapies include intravenous immunoglobulin,
      plasmapheresis, immunoadsorption, extracorporeal photochemotherapy, biological
      agents, as well as experimental therapies such as cholinergic receptor agonists,
      Dsg3 peptides and a p38 mitogen-activated protein kinase inhibitor. Current
      limitations to the widespread use of these therapies include cost, a lack of
      consistent data regarding their benefit, limited availability, and the
      experimental nature of some of the treatments. This review highlights the latest
      case reports and studies that employ established as well as new therapeutics in a
      novel way to treat this rare, but serious, disorder.

PMID- 19761277
TI  - Medication use and increased risk of falls in hospitalized elderly patients: a
      retrospective, case-control study.
AB  - BACKGROUND: Falls in the elderly are common and often serious. Several drugs have
      been associated with increased fall risk. Older adults often take numerous
      medications for multiple chronic conditions, so are at increased risk for drugs
      that potentially cause falls. OBJECTIVE: We studied the association between drug
      use and falls in recently hospitalized older people in order to identify
      medications that may increase the risk of falls in this population. METHODS: A
      retrospective case control study was performed in the geriatric department of
      Bertinot Juel Hospital, Chaumont en Vexin, Picardy, France. We assessed the
      incidence of patient falls during hospitalization in 2004 and 2005 in an acute
      geriatric ward. We compared medications taken by all patients who fell (134
      cases) with those taken by patients who did not fall (126 controls). The 260
      participants were all aged >or=65 years. RESULTS: 50% of falls occurred in the
      first week after admission. In 16% of cases, falls were classified as severe. The
      characteristics of the two groups (patients who fell and those who did not) were
      similar: no significant differences were observed in terms of age, sex, number of
      medicines or prevalence of hypertension or Parkinson's disease. The probability
      of falls increased when the patients used zolpidem (adjusted odds ratio [AOR]
      2.59; 95% CI 1.16, 5.81; p = 0.02), meprobamate (AOR 3.01; 95% CI 1.36, 6.64; p =
      0.01) or calcium channel antagonists (AOR 2.45; 95% CI 1.16, 4.74; p = 0.02).
      CONCLUSIONS: Some drugs are associated with an increased risk of falls in the
      elderly and, when alternatives exist, should be avoided until cohort studies are
      conducted to confirm or refute these possible increased risks.

PMID- 19761275
TI  - Chronic obstructive pulmonary disease: an update on diagnosis and management
      issues in older adults.
AB  - Chronic obstructive pulmonary disease (COPD) is a debilitating disease of the
      elderly that causes significant morbidity and mortality. Despite being a
      treatable and preventable disease, the prevalence continues to rise because of
      the worldwide epidemic of smoking. COPD is associated with enormous healthcare
      costs. It has systemic effects, and common co-morbid conditions such as
      cardiovascular disease, muscle wasting and osteoporosis may all be linked through
      a common systemic inflammatory cascade. Depression, anxiety and malnutrition are
      also common in elderly COPD patients. These factors not only affect quality of
      life (QOL) but also compliance with therapy. Malnutrition is an independent
      predictor of mortality and poor outcome. Spirometry is essential for the
      diagnosis of COPD, but the criteria defining airflow limitation are not clear cut
      for elderly patients and could result in over-diagnosis. However, older patients
      perceive their symptoms differently, and COPD could also be under-diagnosed in
      this population. Acute exacerbations result in worsening symptoms that
      necessitate additional treatment, and may cause a more rapid decline in lung
      function and QOL. The management of elderly patients with COPD should encompass a
      multidisciplinary approach. An evaluation of patients' nutritional status and
      mental health should be undertaken, in addition to assessing their lung function
      and functional impairment. Significant underlying co-morbidities should be
      evaluated and treated to derive the maximal benefit of therapy. Specific therapy
      for COPD should start with cessation of exposure to the most important risk
      factor, tobacco smoke. Smoking cessation rates in the elderly have not declined,
      and this may reflect an underlying reluctance by physicians to counsel and offer
      smoking cessation therapies to the elderly. Unlike oxygen therapy in hypoxaemic
      patients, bronchodilators and corticosteroids do not decrease mortality in COPD
      patients and they are primarily directed towards symptom relief. However, they do
      have a positive effect on QOL and exacerbation rates. The choice of delivery
      devices for inhaled medications is important in the elderly, and patients'
      inhaler technique and manual dexterity should be frequently assessed. Pulmonary
      rehabilitation and nutritional supplementation are other important components of
      care. End-of-life issues should be adequately addressed in the elderly with COPD,
      and an approach integrating curative and palliative interventions is recommended.

PMID- 19761278
TI  - Effects of potentially inappropriate psychoactive medications on falls in US
      nursing home residents: analysis of the 2004 National Nursing Home Survey
      database.
AB  - BACKGROUND AND OBJECTIVE: Use of potentially inappropriate psychoactive
      medications (PIPMs) poses a serious threat of falls among elderly nursing home
      residents. This study was conducted to identify the effects of PIPMs on falls
      compared with use of other psychoactive medications among elderly US nursing home
      residents. METHODS: The 2004 National Nursing Home Survey (NNHS) was used as the
      data source. Logistic regression was performed to ascertain the relationship
      between elderly residents who fell in the past 30 days and the use of PIPMs as
      per Beers' criteria in the presence of other risk factors. The data analysis was
      performed using SAS version 9.1. RESULTS: The 2004 NNHS database includes data
      concerning 11 940 elderly residents in 1174 facilities. The mean age of the
      elderly residents was 84.1 +/- 7.97 years. Residents receiving PIPMs were at an
      increased risk of falling compared with those receiving other psychoactive
      medications (odds ratio [OR] = 0.830, p = 0.028) as well as compared with
      residents not receiving psychoactive medications (OR = 0.624, p < 0.001). In
      addition, residents' fall risk increased with an increase in the number of
      impaired activities of daily living (OR = 1.160, p < 0.001). Presence of
      depressed mood indicators was also identified as an important risk factor (OR =
      1.256, p < 0.001). Use of bedrails had a protective effect on residents' fall
      risk (OR = 0.714, p < 0.001). Demographic factors such as male sex and White race
      were also significant fall-risk factors. CONCLUSION: Prevention of falls in
      elderly nursing home residents remains a challenge. Despite the recommendations
      of prescribing guidelines, PIPMs are still prescribed to elderly nursing home
      residents. Access to appropriate psychoactive medications should be ensured.
      Residents with the identified risk factors should be closely monitored. Further
      research should be pursued to evaluate the impact on falls of potentially
      inappropriate medications in other therapeutic categories.

PMID- 19761279
TI  - Determinant factors of osteoporosis patients' reported therapeutic adherence to
      calcium and/or vitamin D supplements: a cross-sectional, observational study of
      postmenopausal women.
AB  - BACKGROUND: Among the various treatments for osteoporosis, calcium and/or vitamin
      D supplements are frequently included. OBJECTIVE: The objective of the study was
      to analyse adherence to calcium and/or vitamin D treatment and to identify
      related predictors of non-adherence in a sample of postmenopausal women treated
      for osteoporosis in primary care. METHODS: A cross-sectional, observational study
      was conducted in a sample of postmenopausal women receiving pharmaceutical
      treatment for osteoporosis with vitamin D and/or calcium. Sociodemographic,
      general and osteoporosis-related data were collected. Patient's perceptions of
      the adverse effects of treatment, their knowledge of osteoporosis (Batalla test),
      their attitude towards treatment (Morisky-Green test) and their self-reported
      therapeutic adherence (Haynes-Sackett test) were assessed. RESULTS: Of 630 women
      (mean age +/- SD 64.1 +/- 8.7 years) evaluated, 36.2% (95% CI 32.4, 39.9) had
      problems with treatment tolerability, 63.5% (95% CI 59.7, 67.3) had good
      knowledge of osteoporosis, 20.5% (95% CI 17.3, 23.6) had a good attitude to
      treatment and 50.0% (95% CI 46.1, 53.9) had good self-reported adherence to
      treatment. Patients in the poor adherence group had higher mean body mass index
      (p = 0.014), more concurrent pathologies (p = 0.003), more tolerability problems
      (p < 0.001) and worse attitude to treatment (p < 0.001). The multivariate model
      showed a positive relationship between therapeutic adherence and good attitude to
      treatment (odds ratio [OR] = 11.7; p < 0.001), not having tolerability problems
      (OR = 3.3; p < 0.001) and no polymedication (OR = 0.80; p = 0.017). CONCLUSIONS:
      Only one in two postmenopausal women with osteoporosis who take calcium and/or
      vitamin D have good self-reported therapeutic adherence to this treatment.
      Determinant factors of adherence to calcium and/or vitamin D treatment were
      patient's attitude to the treatment, tolerability problems with the treatment and
      number of concurrent treatments.

PMID- 19761280
TI  - Sedative load and mortality among residents of long-term care facilities: a
      prospective cohort study.
AB  - BACKGROUND: Older people are often prescribed multiple drugs with sedative
      properties. Most research has focused on specific classes of sedative and
      psychotropic drugs. The cumulative effect of taking multiple drugs with sedative
      properties has been termed 'sedative load'. Few previous studies have
      investigated the sedative load among residents of long-term care facilities. No
      previous studies have assessed the possible association between sedative load and
      mortality. OBJECTIVE: The objective of this study was to describe the sedative
      load among residents of long-term care facilities, and to investigate a possible
      association between sedative load and mortality. METHODS: This was a prospective
      cohort study. The study population comprised all 1444 residents of 53 long-term
      care wards in seven hospitals in Helsinki during September 2003. Of the eligible
      residents, 1087 residents or their proxies provided written informed consent to
      participate. Medical, medication and follow-up mortality data were available for
      1004 residents. The main outcome measures were sedative load and all-cause
      mortality. RESULTS: The mean age of the residents was 81.3 (SD 10.9) years, and
      the mean number of regularly used drugs per resident was 7.1 (SD 3.4). Fifteen
      percent of residents were categorized as non-users of sedative drugs, 32% as
      users of some drugs with sedative properties and 53% as residents with a high
      sedative load. There was a bivariate association between having a higher sedative
      load and younger age (p < 0.001), male sex (p = 0.006), not being widowed (p =
      0.001), diagnosis of depression (p < 0.001), diagnosis of psychiatric illness
      other than depression (p < 0.001), not being diagnosed with dementia (p = 0.009)
      and a shorter duration of institutional care (p = 0.02). Unadjusted analysis
      revealed that having a higher sedative load was associated with increased
      survival (p = 0.04, log rank test). However, in the adjusted Cox proportional
      hazard model, only poor nutritional status (hazard ratio [HR] 1.55; 95% CI 1.32,
      1.82), male sex (HR 1.37; 95% CI 1.12, 1.69), increasing age (HR 1.04; 95% CI
      1.03, 1.05) and co-morbidity (HR 1.07; 95% CI 1.02, 1.13) were significantly
      associated with risk of death. CONCLUSIONS: There is a very high rate of sedative
      and psychotropic drug use among residents of long-term care facilities in
      Helsinki. However, having a high sedative load was not associated with an
      increased risk of death. Further research is needed to investigate the possible
      association between sedative load and mortality using alternative models and
      methods, and in different resident populations.

PMID- 19761281
TI  - Pregabalin: in the treatment of postherpetic neuralgia.
AB  - Pregabalin is the pharmacologically active S-enantiomer of 3-aminomethyl-5-methyl
      hexanoic acid. It has a similar pharmacological profile to that of its
      developmental predecessor gabapentin, but had greater analgesic activity in
      rodent models of neuropathic pain. Pregabalin is thought to act by reducing the
      excessive release of several excitatory neurotransmitters by binding to the
      alpha(2)-delta protein subunit of voltage-gated calcium channels. Oral pregabalin
      150-600 mg/day, administered in two or three divided doses, was significantly
      more effective than placebo in relieving pain and improving pain-related sleep
      interference in four randomized, double-blind, multicentre studies of 4-13 weeks'
      duration in patients with postherpetic neuralgia (PHN). Pregabalin achieved a
      faster onset of pain relief than placebo. The median times to the onset of pain
      relief with fixed and flexible doses of pregabalin were 1.5 and 3.5 days compared
      with >4 weeks with placebo. Pregabalin was generally well tolerated when titrated
      over 1 week to fixed dosages (maximum 600 mg/day) in clinical trials in mostly
      elderly PHN patients. Adverse events were usually mild to moderate in severity.

PMID- 19761282
TI  - Interest in rural medicine among osteopathic residents and medical students.
AB  - INTRODUCTION: This study examines US osteopathic residents' and medical students'
      attitudes and willingness to practice in rural medicine. The multiple aims of
      this study were to determine: (1) if there are any significant differences in
      interest in rural medicine among various levels of training; (2) the relative
      age, gender, and race of those who are intending to pursue a career in rural
      health; and (3) whether a number of demographic characteristics (age, race, year
      of study) or participation in a rural elective significantly impacted the
      students' and residents' interest in practicing in a rural area. In particular,
      differences between osteopathic students and residents are emphasized, because
      few previous studies have focused on this topic. METHODS: De-identified, cross
      sectional, descriptive techniques utilizing 2 distinct web-based electronic
      surveys were used in this study. Each survey was sent electronically to medical
      students and physicians-in-training. Statistical methods included means,
      frequencies, and t-tests to determine significant differences among groups.
      Logistic regression was used to determine the impact of various factors on
      overall rural interest for each group. RESULTS: A total of 161 students from two
      osteopathic colleges completed and submitted the survey as well as 51
      residents/fellows from a variety of training programs. Approximately 43% of the
      student respondents and 67% of residents expressed an intention of practicing
      rural medicine. Several notable differences were found among the opinions of
      students and residents, particularly regarding the perceived prestige of rural
      physicians. Among medical students, overall interest in rural practice decreased
      in years 2 to 4; however, there was a positive influence if the students were
      aged 34 years or over. As expected, being raised in a rural area had a positive
      impact on rural interest. Additional findings included the lack of significance
      for gender or race, and the positive influence of taking a rural elective. For
      residents, some results are similar, although interest in rural medicine actually
      increased with time. CONCLUSION: It is imperative that osteopathic medical
      schools recruit individuals who will be most likely to pursue rural medicine, and
      then train them to provide health access for rural populations. Further,
      financial incentives are important to both students and residents, suggesting
      that 'loan forgiveness' programs or scholarships may be useful in promoting rural
      location. In order to facilitate the training of individuals who will likely
      pursue rural medicine, there must be institutional dedication to this goal.

PMID- 19761283
TI  - Perception of dental aesthetics in paediatric dentistry.
AB  - AIM: Assessing the perception of the aesthetic components of the oral health by
      paediatric patients at different stages of the child psychological development of
      Piaget. MATERIALS AND METHODS: Twenty children aged between 21 months and 11
      years, of both sexes, patients of a private clinic, were selected. The present
      study group consisted of patients treated for oral pathologies. A set of similar
      supplies was given to all children and they were asked to do a drawing, whose
      theme was "beautiful teeth and ugly teeth". The drawings were evaluated according
      to the classification of the cognitive development of Piaget. RESULTS: Children
      of all ages clearly represent their perception of what "beautiful teeth" and
      "ugly teeth" are. These representations provide the dental professional a clear
      vision of the child's feeling about dental aesthetics. CONCLUSION: The drawings
      are a useful source of information for assessing the aesthetic perception of
      paediatric patients. The knowledge of the children's aesthetic perception is
      relevant to paediatric dentists because children are conscious about their dental
      aesthetic appearance and that of the other children.

PMID- 19761284
TI  - Nicknames and name calling among a population of Nigerian schoolchildren.
AB  - AIM: The aim of this study was to assess the incidence of nicknames and name
      calling among a sample of Nigerian schoolchildren, to examine the types of names
      reported by the children, the relationship of the nicknames to dental appearance
      and the impact of such nicknames on the children. SUBJECTS AND METHODS: A sample
      consisting of 506 randomly selected children from secondary schools in Ile-Ife,
      Nigeria, were invited to participate in the study. Self- administered pre-tested
      questionnaires were completed independently by the children in their schools. The
      questionnaire related to the incidence of nicknames and teasing, nature,
      frequency, relationship to physical appearance and the effect of such names on
      the children. RESULTS: The incidence of nicknames was found to be high among the
      schoolchildren (77%) with no significant difference between boys and girls.
      Eighty eight percent were called by their nicknames on a daily basis. The
      majority of the nicknames were derived from the children's names (34.9%), while
      others related to their appearance, body features, and personality. The nickname
      was appearance-related in about one third of the children and more often this
      related to the weight of the child (26.77%). The teeth were the source of
      nickname in only 6 (4.7%) of the children with equal occurrence rate in boys and
      girls. CONCLUSION: The results of this study show that being given nicknames is a
      common occurrence in Nigerian schools, one third of which may be appearance
      related with most children indifferent to these nicknames. Dental appearance may
      not be a significant contributor to such names.

PMID- 19761285
TI  - A pilot study about emotional experiences by using CFSS-DS in young patients.
AB  - AIM: The aim of this work is to study fears and anxieties of school age Italian
      children regarding dental experience. In particular, to assess the prevalence of
      this phenomenon and understand its possible correlation with five different
      variables: sex, age, social context, previous dental experiences, and self
      consciousness of fear. MATERIALS AND METHODS: 725 Italian children were divided
      according to five variables, and their anxiety studied through the self-filling
      of the Children's Fear Survey Schedule-Dental Subscale (CFSS-DS). STATISTICAL
      ANALYSIS: The obtained results are descriptive and they are expressed as
      percentage values. For the study of the five variables considered, we have
      carried out a statistical regression analysis, by using the S-PLUS 6.0
      Professional software. RESULTS: 26% of the total sample are anxious about the
      dental experience (total score CFSS-DS >39). The objects of greater anxiety are:
      fear of being admitted to hospital, injections, and the use of drilling
      instruments. Every variable considered in the selection of the sample was
      significant (p <0.05) in explaining and influencing the phenomenon "anxiety". In
      particular, the subjects aged 8, attending the third class of primary school were
      more anxious (they were also the most conscious of their emotional difficulties),
      and so little girls and subjects living in areas of low level of urbanisation and
      those who had never lived previous dental experiences. CONCLUSION: The percentage
      of children who may exhibit more or less serious behaviours to dental treatments,
      including the borderline subjects, is above 50%. So it is easy to realise how
      this problem still exists in clinical dental reality, and it is fundamental for
      the dentist to understand and identify these frequent difficulties.

PMID- 19761286
TI  - Self-perception regarding the need for orthodontic treatment among impoverished
      schoolchildren in Brazil.
AB  - AIM: The objectives of the present study were to assess predictive factors
      associated to self-perception regarding the need for orthodontic treatment among
      170 impoverished schoolchildren. MATERIALS AND METHODS: A cross- sectional study
      was conducted in public schools in the city of Belo Horizonte-MG (Brazil).
      Children's self-perception regarding the need for treatment was assessed using
      the Aesthetic Component of the Index of Orthodontic Treatment Need (IOTN-AC) and
      a questionnaire addressing biopsychosocial factors. The chi-square test and
      multiple logistic regression were used in the data analysis. RESULTS: The
      predictive factors for the self-perception of orthodontic treatment need on the
      part of the impoverished schoolchildren included ridicule from persons close to
      the children regarding the appearance of the teeth (OR 2.81; 95%CI 1.2 to 6.4),
      dissatisfaction with oral aesthetics due to the alignment of the teeth (OR 2.45;
      95%CI 1.1 to 5.4) and missing teeth (OR 3.02; 95%CI 1.0 to 9.23). CONCLUSION: The
      alignment of the teeth, missing teeth and ridicule from others regarding the
      appearance of the teeth are the factors that most strongly influence self-
      perception regarding the need for orthodontic treatment among impoverished
      schoolchildren.

PMID- 19761287
TI  - Facial aesthetics and childhood.
AB  - AIM: The aim of the study is to evaluate attention and perception of parents
      about children's facial aesthetics, the paediatrician's role in early diagnosis
      of these problems and the areas of the face considered as the most important from
      an aesthetic point of view. METHODS: The study was carried out collecting 1214
      questionnaires at paediatricians waiting room in the North of Italy. RESULTS:
      Most parents showed attention toward craniofacial deformities of their children
      and considered the paediatrician's role as very important in early diagnosis.
      Profile was considered more important than the front view and face's areas felt
      as the most important were denture, eyes and nose. CONCLUSION: Despite public
      opinion, adults are concerned not only about the general health and growth of
      their children, but also about their facial aesthetics. They, in fact, not only
      judge aesthetics of the whole face, but also discriminate different views and
      specific areas of the face. They require, for early diagnosis of dentofacial
      problems, skilled attention from the paediatrician.

PMID- 19761288
TI  - Preliminary validation of the Brazilian version of the Child Perceptions
      Questionnaire 8-10.
AB  - AIM: The aim of the study was to perform a preliminary validation of the
      Brazilian version of the Child Perceptions Questionnaire 8-10 (CPQ 8-10).
      METHODS: The sample used to test the measurement equivalence was made up of 59
      children from 8 to 10 years of age at the Federal University of Minas Gerais,
      Brazil. The CPQ 8-10 was administered, and clinical exams were performed by a
      single examiner, calibrated for the diagnosis of dental caries (Kappa= 0.98) and
      malocclusion (weighted Kappa and intraclass correlation coefficient = 0.66-1.00).
      The children were divided into three groups according to their clinical condition
      (22 with cavitated carious lesions; 20 with malocclusion; 17 with both oral
      conditions). STATISTICS: The internal consistency of the instrument was assessed
      by Cronbach's alpha Coefficient. The Intraclass correlation coefficient (ICC) was
      used for the test-retest reliability (40 children). Discriminant validity was
      determined using the Kruskal-Wallis test. RESULTS: An assessment of the
      psychometric properties revealed the instrument to be reliable (Cronbach's
      alpha=0.92 for the total scale and 0.63-0.85 for the subscales), exhibiting
      excellent stability (ICC=0.96 for the total scale and 0.79-0.95 for the
      subscales). Construct validity was demonstrated through the significant
      correlations between the global indicators and subscales. There were
      statistically significant differences between the clinical groups regarding the
      total scale, thereby demonstrating discriminant validity (p=0.03). CONCLUSIONS:
      The preliminary validation of the Brazilian version of the CPQ 8-10 showed valid
      and reliable for use on Brazilian children.

PMID- 19761289
TI  - Family Impact Scale (FIS): psychometric properties of the Brazilian Portuguese
      language version.
AB  - AIM: Evaluate the psychometric properties of the Brazilian version of the Family
      Impact Scale (FIS). METHODS: Following translation and cross-cultural adaptation,
      the FIS was tested on 123 parents-caregivers of children between 11 and 14 years
      of age with dental caries and malocclusions. The parents were recruited from the
      Paediatric Dental and Orthodontic clinics where their children were receiving
      dental care. Psychometric properties were assessed through internal consistency,
      test-retest reliability, construct validity and discriminant validity. RESULTS:
      The mean FIS score was 6.97 (SD 7.81) for the dental caries group and 7.25 (SD
      7.70) for the malocclusion group. The FIS score was unable to discriminate
      different family impact caused by children's oral health conditions. Internal
      consistency was confirmed by a Cronbach's alpha coefficient of 0.79. Test-retest
      reliability revealed good reproducibility (ICC 0.83). Construct validity was
      good, demonstrating highly significant correlations between parent's perceptions
      regarding the overall wellbeing indicator for their children and the total FIS
      and subscales. Financial burden demonstrated no significant correlation with
      global indicators. CONCLUSIONS: Overall psychometric results for the Brazilian
      version of the FIS confirm it as a reliable, valid questionnaire for assessing
      the family impact caused by children's oral conditions.

PMID- 19761290
TI  - A case report on autosomal recessive Robinow syndrome.
AB  - BACKGROUND: Robinow syndrome or "foetal face" syndrome is an extremely rare
      genetic disorder with characteristic skeletal and orofacial findings. The purpose
      of the present case report is to describe the clinical findings of an 8 year-old
      female patient with autosomal recessive Robinow syndrome. CASE REPORT: The
      patient was born to consanguineous parents and had anomalies typical of the
      recessive type of the syndrome such as short stature, mesomelic limb shortening,
      vertebral anomalies and dysmorphic facial features. Besides typical orodental
      findings, she also had root malformation in mandibular incisors, which is unusual
      finding of recessive type of Robinow syndrome. This case report emphasizes the
      importance of oral and dental manifestations of this syndrome.

PMID- 19761291
TI  - Semi talon and trace talon: report of two cases.
AB  - BACKGROUND: Talon cusp is a relatively rare developmental anomaly characterised
      by the presence of an accessory cusp-like structure projecting from the cingulum
      area or cemento-enamel junction of the maxillary or mandibular anterior teeth in
      both the primary and permanent dentition. It is frequently seen in the permanent
      laterals. CASE REPORT: The paper presents two cases of talon cusp of semi talon
      and trace talon type.

PMID- 19761292
TI  - Long-lasting modulation of feature integration by transcranial magnetic
      stimulation.
AB  - The human brain analyzes a visual object first by basic feature detectors. On the
      objects way to a conscious percept, these features are integrated in subsequent
      stages of the visual hierarchy. The time course of this feature integration is
      largely unknown. To shed light on the temporal dynamics of feature integration,
      we applied transcranial magnetic stimulation (TMS) to a feature fusion paradigm.
      In feature fusion, two stimuli which differ in one feature are presented in rapid
      succession such that they are not perceived individually but as one single
      stimulus only. The fused percept is an integration of the features of both
      stimuli. Here, we show that TMS can modulate this integration for a surprisingly
      long period of time, even though the individual stimuli themselves are not
      consciously perceived. Hence, our results reveal a long-lasting integration
      process of unconscious feature traces.

PMID- 19761293
TI  - Color-selective attention need not be mediated by spatial attention.
AB  - It is well-established that attention can select stimuli for preferential
      processing on the basis of non-spatial features such as color, orientation, or
      direction of motion. Evidence is mixed, however, as to whether feature-selective
      attention acts by increasing the signal strength of to-be-attended features
      irrespective of their spatial locations or whether it acts by guiding the
      spotlight of spatial attention to locations containing the relevant feature. To
      address this question, we designed a task in which feature-selective attention
      could not be mediated by spatial selection. Participants observed a display of
      intermingled dots of two colors, which rapidly and unpredictably changed
      positions, with the task of detecting brief intervals of reduced luminance of 20%
      of the dots of one or the other color. Both behavioral indices and
      electrophysiological measures of steady-state visual evoked potentials showed
      selectively enhanced processing of the attended-color items. The results
      demonstrate that feature-selective attention produces a sensory gain enhancement
      at early levels of the visual cortex that occurs without mediation by spatial
      attention.

PMID- 19761294
TI  - Integration of vision and haptics during tool use.
AB  - When integrating signals from vision and haptics the brain must solve a
      "correspondence problem" so that it only combines information referring to the
      same object. An invariant spatial rule could be used when grasping with the hand:
      here the two signals should only be integrated when the estimate of hand and
      object position coincide. Tools complicate this relationship, however, because
      visual information about the object, and the location of the hand, are separated
      spatially. We show that when a simple tool is used to estimate size, the brain
      integrates visual and haptic information in a near-optimal fashion, even with a
      large spatial offset between the signals. Moreover, we show that an offset
      between the tool-tip and the object results in similar reductions in cross-modal
      integration as when the felt and seen positions of an object are offset in normal
      grasping. This suggests that during tool use the haptic signal is treated as
      coming from the tool-tip, not the hand. The brain therefore appears to combine
      visual and haptic information, not based on the spatial proximity of sensory
      stimuli, but based on the proximity of the distal causes of stimuli, taking into
      account the dynamics and geometry of tools.

PMID- 19761295
TI  - Accommodative lag and fluctuations when optical aberrations are manipulated.
AB  - We evaluated the accommodative response to a stimulus moving from 0 to 6 D
      following a staircase function under natural, corrected, and induced optical
      aberrations, using an adaptive-optics (AO) electromagnetic deformable mirror. The
      accommodative response of the eye (through the mirror) and the change of
      aberrations were measured on 5 subjects using a Hartmann-Shack wavefront sensor
      operating at 12.8 Hz. Five conditions were tested: (1) natural aberrations, (2)
      AO correction of the unaccommodated state and induction (over 6-mm pupils) of (3)
      +1 microm and (4) -1 microm of spherical aberration and (5) -2 microm of vertical
      coma. Four subjects showed a better accommodative response with AO correction
      than with their natural aberrations. The induction of negative spherical
      aberration also produced a better accommodative response in the same subjects.
      Accommodative lag increased in all subjects when positive spherical aberration
      and coma were induced. Fluctuations of the accommodative response (computed
      during each 1-D period of steady accommodation) increased with accommodative
      response when high-order aberrations were induced. The largest fluctuations
      occurred for induced negative spherical aberration and the smallest for natural
      and corrected aberrations. The study demonstrates that aberrations influence
      accommodative lag and fluctuations of accommodation and that correcting
      aberrations improves rather than compromises the accommodative response.

PMID- 19761296
TI  - Background motion and the perception of shape defined by illusory contours.
AB  - A Kanizsa triangle is usually generated by placing three circular tokens, with
      deleted wedges, at the apexes of an equilateral triangle. If the token angles do
      not each subtend 60 degrees, a Kanizsa triangle may still be evident, but with
      illusory contours that appear to be curvilinear. We investigated whether this
      curved-contour distortion in shape can be nulled by radial background image
      motion utilizing a two-alternative forced-choice procedure. We report that a test
      Kanizsa figure with concave illusory contours appeared to form a perfectly
      regular equilateral triangle when it was superimposed on a globally expanding
      pattern. Conversely, a test Kanizsa triangle with convex illusory contours was
      perceived as regular when it was superimposed on a globally contracting pattern.
      This distortion effect was most distinct for fast dot speeds and was greater for
      contracting motion. Additionally, the effect was observed regardless of a
      polarity difference between background dots and tokens. However, shape distortion
      was not evident when the Kanizsa figure was defined by "real," luminance-defined,
      contours. Our findings support the conclusion that background image motion plays
      an important role in the perception of shape, especially when there is an
      "insufficiency" in the position information that specifies the shape's contours.

PMID- 19761297
TI  - Implicitly perceived objects attract gaze during later free viewing.
AB  - Everyday life frequently requires searching for objects in the visual scene.
      Visual search is typically accompanied by a series of eye movements. In an effort
      to explain subjects' scanning patterns, models of visual search propose that a
      template of the target is used, to guide gaze (and attention) to locations which
      exhibit "suspicious" similarity to this template. We show here that the scanning
      patterns are also clearly influenced by implicit (unrecognized) cues: A backward
      masked object, presented before the scene display, automatically attracts gaze to
      its corresponding location in the following inspected image. Interestingly,
      subliminally observed words describing objects do not have the same effect. This
      demonstrates that visual search can be unconsciously guided by activated target
      representations at the perceptual level, but it is much less affected by implicit
      information at the semantic level. Implications on search models are discussed.

PMID- 19761298
TI  - The temporal advantage for individuating objects of expertise: perceptual
      expertise is an early riser.
AB  - The identification of faces has a temporal advantage over that of other object
      categories. The orientation-specific nature of this advantage suggests that it
      stems from our extensive experience and resulting expertise with upright faces.
      While experts can identify objects faster than novices, it is unclear exactly how
      the temporal dynamics of identification are changed by expertise and whether the
      nature of this temporal advantage is similar for face and non-face objects of
      expertise. Here, we titrated encoding time using a backward-masking paradigm with
      variable stimulus-mask onset-asynchronies and mapped the resulting effect on
      recognition for upright and inverted faces (Experiment 1) and for cars among car
      experts and car novices (Experiment 2). Performance for upright faces and cars
      among car experts rose above chance between 33 and 70 ms before that for inverted
      faces or cars among car novices. A shifted exponential function fitted to these
      data suggested that performance started to rise earlier for experts than for
      novices, but that additional encoding time increased performance at a similar
      rate. Experience influences the availability of information early in processing,
      possibly through the recruitment of more category-selective neurons, while the
      rate of perceptual processing may be less flexible and limited by inherent
      physiological constraints.

PMID- 19761299
TI  - The initial representation of individual faces in the right occipito-temporal
      cortex is holistic: electrophysiological evidence from the composite face
      illusion.
AB  - Identifying a facial feature (e.g. the eyes) is influenced by the position and
      identity of other features (e.g. the mouth) of the face, supporting the view that
      an individual face is represented as a whole in the human brain. To clarify how
      early in the time-course of face processing this holistic individual
      representation is accessed we recorded event-related potentials during an
      adaptation paradigm of the composite face illusion (CFI). Observers performed a
      matching task on top halves of two faces presented sequentially. For each face
      pair, top and bottom face halves could be both identical, both different, or only
      the bottom half differed. The signal was larger over the right occipito-temporal
      cortex at about 160 ms (N170) when the attended top half differed between the two
      faces than when identical top halves were repeated. Crucially, a larger N170 was
      also found when the top halves of the two faces were the same, yet the observers
      had the illusion that they differed (CFI). This effect was not found when the two
      face halves were spatially misaligned. These observations indicate that the
      earliest perceptual representation of an individual face in the human brain is
      holistic rather than based on independent face parts.

PMID- 19761300
TI  - Stereo and motion Dmax in infants.
AB  - These experiments compared the maximum displacement and disparity limits (Dmax)
      for apparent motion and stereopsis in random-dot displays in adult and 12-28 week
      old infant subjects. Both stereo and motion Dmax increased during development,
      from about 0.3 deg in the youngest infants to 2 deg in adults. Some of the
      younger infants (12-14 weeks) did not give a stereo threshold, probably because
      stereopsis had not yet developed; but otherwise, the values of Dmax in the two
      domains were close to each other throughout the age range. These results suggest
      that both stereo and motion Dmax are limited by some common factor. Possible
      factors include receptive field sizes and internal noise. Simulations in which
      these were varied showed that while changes in both could contribute to the
      development of Dmax, only an increase in receptive field size can fully account
      for the rise in Dmax with age.

PMID- 19761301
TI  - Asymmetric interaction between motion and stereopsis revealed by concurrent
      adaptation.
AB  - Although contingent aftereffects between motion and stereopsis have been referred
      to as behavioral evidence for the joint processing of the two features, the
      reciprocal nature of encoding the two features has not been systematically
      studied. Using a novel form of concurrent adaptation, we probed the perception of
      direction- and disparity-defined coherent surfaces in parallel before and after
      adaptation to a stimulus that moved in a single direction at a particular
      binocular disparity. Contrary to earlier findings, we found a strong asymmetry
      between motion and stereopsis: the detection of disparity signal after adaptation
      was more impaired when the test stimulus was moving in the adapted direction than
      in the non-adapted direction, whereas the test disparity hardly affected the
      detection of coherent motion. However, motion adaptation became dependent on
      disparity when we added another surface that was moving in the opposite direction
      at the opposite sign of disparity to those of the original adaptor, as in
      previous studies of contingent aftereffects. The observed asymmetric contingency
      between motion and disparity adaptation urges the reinterpretation of previously
      reported contingent aftereffects and suggests a corresponding asymmetry between
      neural mechanisms devoted to processing of motion and stereopsis in human visual
      cortex.

PMID- 19761302
TI  - Short- and long-term plasticity of eye position information: examining
      perceptual, attentional, and motor influences on perisaccadic perception.
AB  - Spatial vision requires information about eye position to account for eye
      movements. But integrating eye position information and information about objects
      in the world is imperfect and can lead to transient misperceptions around the
      time of saccadic eye movements most likely because the signals are prone to
      temporal errors making it difficult to tell when the retinas move relative to
      when retinal images move. To clarify where this uncertainty comes from, in four
      experiments we examined influences of eye posture, attentional cueing, and trial
      history on perisaccadic misperceptions. We found evidence for one longer-term
      modulation of perisaccadic shift that evolved over the time of the test session
      due to biased eye posture. Another, short-term influence on perisaccadic shift
      was related to eye posture during preceding trials or the direction of the
      preceding saccade. Both perceptual effects could not be explained with visual
      delays, influences of attention or changes in saccade metrics. Our data are
      consistent with the idea that perisaccadic shift is caused by neural
      representations of eye position or space that are plastic and that arise from non
      motor, extraretinal mechanisms. This suggests a perceptual system that
      continuously calibrates itself in response to changes in oculomotor and muscle
      systems to reconstruct a stable percept of the world.

PMID- 19761303
TI  - Blur on the retina due to higher-order aberrations: comparison of eye growth
      models to experimental data.
AB  - In the simplest model of eye growth, the ocular optics uniformly scale upwards,
      as do monochromatic higher-order aberrations (HOA) and linear blur on the retina.
      However, measured HOA remain constant or decrease with growth in some species. A
      new model, which holds HOA and the associated linear blur on the retina constant,
      was used to predict changes in HOA and resulting image quality on the retina
      during growth, in each of chick, monkey, and human. Models used rates of growth
      in each of the three species. Angular optical quality on the retina due to HOA,
      and its metrics improved, in contrast to the constancy predicted by uniform
      scaling. The model with constant linear HOA blur predicts well the improvement in
      human optical quality between infant and adult. Overall, in chick and monkey,
      angular blur improves at a rate faster than that predicted by the constant linear
      blur model, implying that linear retinal blur due to HOA decreases with age. On
      the other hand, in chick, angular blur due to third-order aberrations decreased
      at a rate predicted by the constant linear blur model. Growth changes in retinal
      blur due to HOA are species dependent but can be better understood by comparison
      with the new model predictions.

PMID- 19761304
TI  - The influence of shape and skeletal axis structure on texture perception.
AB  - We studied the relationship between texture orientation and shape skeletal axes
      in two tasks related to texture perception. The first series of experiments
      investigated discrimination of texture-defined shapes. We found that alignment
      between texture orientation and the skeletal axis of a figural region improved
      the segmentation strength, as did a perpendicular arrangement to a lesser extent.
      The alignment effect is attributable to the orientation of the skeletal axis
      itself, not the orientation of the figure edges; these two factors were
      deconfounded by the use of shapes whose contours undulated relative to the main
      axis orientation. Discrimination of multi-part shapes additionally showed that
      local alignment of texture with the axis of the enclosing part gave superior
      segmentation performance when compared to the classically optimal case of uniform
      texture orientation. A second series of experiments investigated sensitivity to
      changes in texture orientation within texture patches. Texture orientation
      discrimination was heightened when texture was aligned with the axis of the patch
      shape, demonstrating that the "axis effect" also affects the encoding of texture
      orientation. Taken together, these findings point to a broad role of skeletal
      axes in influencing the processes by which texture elements are aggregated to
      form the object itself.

PMID- 19761305
TI  - A new "tilt" illusion reveals the relation between border ownership and border
      binding.
AB  - The "association field" models of contour detection predict specific spatial
      conditions for linking or grouping neighboring elements into smooth contours. We
      previously suggested that the "association field" model may account for
      perceptual binding of near-collinear luminance edges of same contrast polarity
      and their consequent unification into a unique contrast border with illusory
      tilt. This approach is now developed into a new version of the tilt illusion, the
      seesaw illusion, in which the contrast border is perceived as inverting concave
      convex illusory curvature when background luminance is inverted, indicating that
      contrast polarity must be incorporated into the notion of "association field" to
      account for the seesaw illusion. We found that although tile-edge segmentation
      into alternating black-white segments produces conflicting local tilts, the
      illusion remains, up to 16 arcmin edge distance. This occurs at extreme
      background luminance for long segments (where only congruent edge segments of
      higher contrast bind, the others being perceptually assimilated into the
      background surface) and, when segments are too short for their orientation to be
      detected, at all background luminance values except that equidistant from black
      and white stripes. Our findings provide further confirmation that these are
      striking border ownership phenomena, demonstrating that figure/ground
      organization precedes perceptual binding of edges through association fields.

PMID- 19761306
TI  - Critical features for the perception of emotion from gait.
AB  - Human observers readily recognize emotions expressed in body movement. Their
      perceptual judgments are based on simple movement features, such as overall
      speed, but also on more intricate posture and dynamic cues. The systematic
      analysis of such features is complicated due to the difficulty of considering the
      large number of potentially relevant kinematic and dynamic parameters. To
      identify emotion-specific features we motion-captured the neutral and emotionally
      expressive (anger, happiness, sadness, fear) gaits of 25 individuals. Body
      posture was characterized by average flexion angles, and a low-dimensional
      parameterization of the spatio-temporal structure of joint trajectories was
      obtained by approximation with a nonlinear mixture model. Applying sparse
      regression, we extracted critical emotion-specific posture and movement features,
      which typically depended only on a small number of joints. The features we
      extracted from the motor behavior closely resembled features that were critical
      for the perception of emotion from gait, determined by a statistical analysis of
      classification and rating judgments of 21 observers presented with avatars
      animated with the recorded movements. The perceptual relevance of these features
      was further supported by another experiment showing that artificial walkers
      containing only the critical features induced high-level after-effects matching
      those induced by adaptation with natural emotional walkers.

PMID- 19761307
TI  - Adaptation and prolonged inhibition as a main cause of motion-induced blindness.
AB  - Motion-induced blindness (MIB) is one of the most enigmatic perceptual
      disappearance phenomena. Here we suggest that MIB may be caused by the combined
      effects of two distinct adaptation processes: one shared with two other non-MIB
      configurations and entailing a response-gain reduction, and a second, MIB
      specific transient-to-sustained incremental inhibition causing a contrast-gain
      reduction. Response-gain reduction is evidenced by brightness-tracking experiment
      where the 1-minute brightness time course of an MIB target is compared to the
      time courses of the same target superimposed on a static mask (SM) and on no mask
      at all (absent mask; AM). MIB and SM yield about the same brightness time courses
      with a faster initial drop and reaching a lower plateau than AM. While the
      frequency of phenomenal suppressions and their duration are very much reduced
      under SM and AM conditions, they increase as for MIB within the first 5-15 s of
      inspection and level off thereafter. Contrast-gain reduction over time is
      evidenced in a detection experiment showing that MIB target thresholds are higher
      and increase more steeply with inspection time than AM or SM thresholds. The
      interplay between these noisy adaptation and prolonged inhibition processes may
      well account for MIB's specificity.

PMID- 19761308
TI  - Peripheral optical errors and their change with accommodation differ between
      emmetropic and myopic eyes.
AB  - The progression of myopia is thought to be controlled by the retinal image
      quality, but its triggering factors are not yet well known. The differences
      between the peripheral optics in emmetropic and myopic eyes might explain why
      some eyes become myopic. The present study further investigates peripheral
      optical quality and how it is affected by accommodation. The refraction and
      aberrations of the right eyes of five emmetropes and five myopes were measured
      using a laboratory Hartmann-Shack wave front sensor, specially designed for
      peripheral measurements with an open field of view. The off-axis optical quality
      was assessed in steps of 10 degrees out to +/-40 degrees horizontally and +/-20
      degrees vertically for two different states of accommodation (targets at 0.5 D
      and 4.0 D). As expected, the emmetropes had a higher relative peripheral myopia,
      that is, more positive c(2)(0) coefficient, than the myopes. The new results of
      this study are that this well-known difference was found to be asymmetric over
      the visual field and that it increased with accommodation. This increase was
      because the relative peripheral defocus profile of the myopes did not show a
      consistent change between far and near vision, whereas the emmetropes became
      relatively more myopic in the periphery with accommodation. These findings may
      indicate a difference between emmetropic and myopic eyes that could be an
      important clue to understand myopia progression.

PMID- 19761310
TI  - Understanding rapid category detection via multiply degraded images.
AB  - Rapid category detection, as discovered by S. Thorpe, D. Fize, and C. Marlot
      (1996), demonstrated that the human visual system can detect object categories in
      natural images in as little as 150 ms. To gain insight into this phenomenon and
      to determine its relevance to naturally occurring conditions, we degrade the
      stimulus set along various image dimensions and investigate the effects on
      perception. To investigate how well modern-day computer vision algorithms cope
      with degradations, we conduct an analog of this same experiment with state-of-the
      art object recognition algorithms. We discover that rapid category detection in
      humans is quite robust to naturally occurring degradations and is mediated by a
      non-linear interaction of visual features. In contrast, modern-day object
      recognition algorithms are not as robust.

PMID- 19761309
TI  - Holistic crowding of Mooney faces.
AB  - An object or feature is generally more difficult to identify when other objects
      are presented nearby, an effect referred to as crowding. Here, we used Mooney
      faces to examine whether crowding can also occur within and between holistic face
      representations (C. M. Mooney, 1957). Mooney faces are ideal stimuli for this
      test because no cues exist to distinguish facial features in a Mooney face; to
      find any facial feature, such as an eye or a nose, one must first holistically
      perceive the image as a face. Through a series of six experiments we tested the
      effect of crowding on Mooney face recognition. Our results demonstrate crowding
      between and within Mooney faces and fulfill the diagnostic criteria for crowding,
      including eccentricity dependence and lack of crowding in the fovea, critical
      flanker spacing consistent with less than half the eccentricity of the target,
      and inner-outer flanker asymmetry. Further, our results show that recognition of
      an upright Mooney face is more strongly impaired by upright Mooney face flankers
      than inverted ones. Taken together, these results suggest crowding can occur
      selectively between high-level representations of faces and that crowding must
      occur at multiple levels in the visual system.

PMID- 19761311
TI  - Does the chromatic Mach bands effect exist?
AB  - The achromatic Mach bands effect is a well-known visual illusion, discovered over
      a hundred years ago. This effect has been investigated thoroughly, mainly for its
      brightness aspect. The existence of Chromatic Mach bands, however, has been
      disputed. In recent years it has been reported that Chromatic Mach bands are not
      perceived under controlled iso-luminance conditions. However, here we show that a
      variety of Chromatic Mach bands, consisting of chromatic and achromatic regions,
      separated by a saturation ramp, can be clearly perceived under iso-luminance and
      iso-brightness conditions. In this study, observers' eye movements were recorded
      under iso-brightness conditions. Several observers were tested for their ability
      to perceive the Chromatic Mach bands effect and its magnitude, across different
      cardinal and non-cardinal Chromatic Mach bands stimuli. A computational model of
      color adaptation, which predicted color induction and color constancy,
      successfully predicts this variation of Chromatic Mach bands. This has been
      tested by measuring the distance of the data points from the "achromatic point"
      and by calculating the shift of the data points from predicted complementary
      lines. The results suggest that the Chromatic Mach bands effect is a specific
      chromatic induction effect.

PMID- 19761312
TI  - Is attention essential for inducing synesthetic colors? Evidence from oculomotor
      distractors.
AB  - In studies investigating visual attention in synesthesia, the targets usually
      induce a synesthetic color. To measure to what extent attention is necessary to
      induce synesthetic color experiences, one needs a task in which the synesthetic
      color is induced by a task-irrelevant distractor. In the current study, an
      oculomotor distractor task was used in which an eye movement was to be made to a
      physically colored target while ignoring a single physically colored or
      synesthetic distractor. Whereas many erroneous eye movements were made to
      distractors with an identical hue as the target (i.e., capture), much less
      interference was found with synesthetic distractors. The interference of
      synesthetic distractors was comparable with achromatic non-digit distractors.
      These results suggest that attention and hence overt recognition of the inducing
      stimulus are essential for the synesthetic color experience to occur.

PMID- 19761313
TI  - Dynamics of chromatic visual system processing differ in complexity between
      children and adults.
AB  - Measures of chromatic contrast sensitivity in children are lower than those of
      adults. This may be related to immaturities in signal processing at or near
      threshold. We have found that children's VEPs in response to low contrast supra
      threshold chromatic stimuli are more intra-individually variable than those
      recorded from adults. Here, we report on linear and nonlinear analyses of
      chromatic VEPs recorded from children and adults. Two measures of signal-to-noise
      ratio are similar between the adults and children, suggesting that relatively
      high noise is unlikely to account for the poor clarity of negative and positive
      peak components in the children's VEPs. Nonlinear analysis indicates higher
      complexity of adults' than children's chromatic VEPs, at levels of chromatic
      contrast around and well above threshold.

PMID- 19761314
TI  - Cross-cultural perceptions of facial resemblance between kin.
AB  - Humans use facial comparisons to identify their relatives and adjust their
      behavior accordingly. However, the mechanisms underlying the assessment of facial
      similarities are poorly known. Here, we investigate the role of exposure to
      particular faces for the detection of facial similarities by asking judges to
      detect parent-child pairs using faces from different origins. In a first phase,
      French and Senegalese judges assessed facial resemblance in French and Senegalese
      families. In a second phase, Senegalese judges who had immigrated to France, as
      well as French and Senegalese stationary judges, were asked to rate a second set
      of Senegalese and French families. The judges showed no differences in their
      ability to detect parent-child pairs in French and Senegalese families in both
      the first and second phases. For judges who changed their country of residence,
      the answer time and duration of stay in the new country were not associated with
      correct assignment rates. Our results suggest that exposure has a limited role in
      the ability to process facial resemblance in others, which contrasts with facial
      recognition processing. We also discuss whether processing facial similarities is
      a by-product of the facial recognition system or an evolved ability to assess
      kinship relationships.

PMID- 19761315
TI  - Behavioral effects of visual field location on processing motion- and luminance
      defined form.
AB  - Traditional theories posit a ventral cortical visual pathway subserving object
      recognition regardless of the information defining the contour. However,
      functional magnetic resonance imaging (fMRI) studies have shown dorsal cortical
      activity during visual processing of static luminance-defined (SL) and motion
      defined form (MDF). It is unknown if this activity is supported behaviorally, or
      if it depends on central or peripheral vision. The present study compared
      behavioral performance with two types of MDF [one without translational motion
      (MDF) and another with (TM)] and SL shapes in a shape matching task where shape
      pairs appeared in the upper or lower visual fields or along the horizontal
      meridian of central or peripheral vision. MDF matching was superior to the other
      contour types regardless of location in central vision. Both MDF and TM matching
      was superior to SL matching for presentations in peripheral vision. Importantly,
      there was an advantage for MDF and TM matching in the lower peripheral visual
      field that was not present for SL forms. These results are consistent with
      previous behavioral findings that show no field advantage for static form
      processing and a lower field advantage for motion processing. They are also
      suggestive of more dorsal cortical involvement in the processing of shapes
      defined by motion than luminance.

PMID- 19761316
TI  - The nonlinear structure of motion perception during smooth eye movements.
AB  - To perceive object motion when the eyes themselves undergo smooth movement, we
      can either perceive motion directly-by extracting motion relative to a background
      presumed to be fixed-or through compensation, by correcting retinal motion by
      information about eye movement. To isolate compensation, we created stimuli in
      which, while the eye undergoes smooth movement due to inertia, only one object is
      visible-and the motion of this stimulus is decoupled from that of the eye. Using
      a wide variety of stimulus speeds and directions, we rule out a linear model of
      compensation, in which stimulus velocity is estimated as a linear combination of
      retinal and eye velocities multiplied by a constant gain. In fact, we find that
      when the stimulus moves in the same direction as the eyes, there is little
      compensation, but when movement is in the opposite direction, compensation grows
      in a nonlinear way with speed. We conclude that eye movement is estimated from a
      combination of extraretinal and retinal signals, the latter based on an
      assumption of stimulus stationarity. Two simple models, in which the direction of
      eye movement is computed from the extraretinal signal and the speed from the
      retinal signal, account well for our results.

PMID- 19761317
TI  - Binocular motor coordination during saccades and fixations while reading: a
      magnitude and time analysis.
AB  - Reading involves saccades and fixations. Misalignment of the eyes should be small
      enough to allow sensory fusion. Recent studies reported disparity of the eyes
      during fixations. This study examines disconjugacy, i.e. change in disparity over
      time, both during saccades and fixations. Text reading saccades and saccades to
      single targets of similar sizes (2.5 degrees ) are compared. Young subjects were
      screened to avoid problems of binocular vision and oculomotor vergence. The
      results show high quality of motor binocular coordination in both tasks: the
      amplitude difference between the saccade of the eyes was approximately 0.16
      degrees ; during the fixation period, the drift difference was only 0.13 degrees
      . The disconjugate drift occurred mainly during the first 48 ms of fixation, was
      equally distributed to the eyes and was often reducing the saccade disconjugacy.
      Quality of coordination regardless of the task is indicative of robust
      physiological mechanisms. We suggest the existence of active binocular control
      mechanisms in which vergence signals may have a central role. Even computation of
      saccades may be based on continuous interaction between saccade and vergence.

PMID- 19761318
TI  - Exploring the spatiotemporal properties of fractal rotation perception.
AB  - A series of three experiments was conducted with the aim of determining the
      processing nature of the fractal rotation stimulus introduced by C. P. Benton, J.
      M. O'Brien, and W. Curran (2007). This stimulus has been proposed to be invisible
      to first-order sensitive mechanisms considering it is drift-balanced. Rather,
      motion perception would require the analysis of spatial structure (orientation)
      changing over time. In Experiment 1, spatiotemporal properties of fractal
      rotation perception have been explored, in comparison with first-order rotation
      perception. In Experiment 2, a motion paradigm similar to the one developed by K.
      Nakayama and C. W. Tyler (1981) and later used by A. E. Seiffert and P. Cavanagh
      (1998) has been used to characterize the motion processing mechanism responsible
      for fractal rotation perception. In Experiment 3, we have used a paradigm similar
      to N. E. Scott-Samuel and A. T. Smith (2000) to evaluate whether fractal rotation
      perception is analyzed by common or distinct mechanisms to those for first-order
      rotation perception. Results indicate that fractal rotation perception involves
      feature-tracking processes with mechanisms responding to global orientation-based
      changes of the image. Given the absence of cancellation of first-order and
      fractal rotation motion signals, we can therefore conclude that the first-order
      and fractal motion sensitive pathways are dissociable at early stages of the
      visual processing stream.

PMID- 19761319
TI  - Quantifying center bias of observers in free viewing of dynamic natural scenes.
AB  - Human eye-tracking studies have shown that gaze fixations are biased toward the
      center of natural scene stimuli ("center bias"). This bias contaminates the
      evaluation of computational models of attention and oculomotor behavior. Here we
      recorded eye movements from 17 participants watching 40 MTV-style video clips
      (with abrupt scene changes every 2-4 s), to quantify the relative contributions
      of five causes of center bias: photographer bias, motor bias, viewing strategy,
      orbital reserve, and screen center. Photographer bias was evaluated by five naive
      human raters and correlated with eye movements. The frequently changing scenes in
      MTV-style videos allowed us to assess how motor bias and viewing strategy
      affected center bias across time. In an additional experiment with 5
      participants, videos were displayed at different locations within a large screen
      to investigate the influences of orbital reserve and screen center. Our results
      demonstrate quantitatively for the first time that center bias is correlated
      strongly with photographer bias and is influenced by viewing strategy at scene
      onset, while orbital reserve, screen center, and motor bias contribute minimally.
      We discuss methods to account for these influences to better assess computational
      models of visual attention and gaze using natural scene stimuli.

PMID- 19761320
TI  - Perceived timing of new objects and feature changes.
AB  - Recent psychophysical studies have shown that perceived timings of events can be
      dissociated from their physical temporal relationship. In the flash-lag effect
      (FLE), a flash presented at the same spatiotemporal position as a continuously
      moving stimulus is perceived to lag behind the moving stimulus. In the present
      study, we report a peculiar condition in which FLE does not occur even when the
      position of a moving object is estimated at the moment of a transient event. In a
      series of experiments, we compared perceived timings and processing delays for
      appearance of a new object against feature changes of an existing object. We
      found that perceived timing of the appearance of a new object is delayed compared
      to the perception of feature changes updating the properties of an object. Our
      results suggest the construction of a new object representation requires
      additional time to establish a stable neuronal representation.

PMID- 19761321
TI  - Learning illumination- and orientation-invariant representations of objects
      through temporal association.
AB  - As the orientation or illumination of an object changes so does its appearance.
      This paper considers how observers are nonetheless able to recognize objects that
      have undergone such changes. In particular the paper tests the hypothesis that
      observers rely on temporal correlations between different object views to decide
      whether they are views of the same object or not. In a series of experiments
      subjects were shown a sequence of views representing a slowly transforming
      object. Testing revealed that subjects had formed object representations which
      were directly influenced by the temporal characteristics of the training views.
      In particular, introducing spurious correlations between views of different
      people's heads caused subjects to regard those views as being of a single person.
      This rapid and robust overriding of basic generalization processes supports the
      view that our recognition system tracks the correlated appearance of views of
      objects across time. Such view associations appear to allow the visual system to
      solve the view invariance problem without recourse to complex illumination models
      for extracting 3D form, or the use of the image plane transformations required to
      make appearance-based comparisons.

PMID- 19761322
TI  - Cue dynamics underlying rapid detection of animals in natural scenes.
AB  - Humans are known to be good at rapidly detecting animals in natural scenes.
      Evoked potential studies indicate that the corresponding neural signals can
      emerge in the brain within 150 msec of stimulus onset (S. Thorpe, D. Fize, & C.
      Marlot, 1996) and eye movements toward animal targets can be initiated in roughly
      the same timeframe (H. Kirchner & S. J. Thorpe, 2006). Given the speed of this
      discrimination, it has been suggested that the underlying visual mechanisms must
      be relatively simple and feedforward, but in fact little is known about these
      mechanisms. A key step is to understand the visual cues upon which these
      mechanisms rely. Here we investigate the role and dynamics of four potential
      cues: two-dimensional boundary shape, texture, luminance, and color. Results
      suggest that the fastest mechanisms underlying animal detection in natural scenes
      use shape as a principal discriminative cue, while somewhat slower mechanisms
      integrate these rapidly computed shape cues with image texture cues. Consistent
      with prior studies, we find little role for luminance and color cues throughout
      the time course of visual processing, even though information relevant to the
      task is available in these signals.

PMID- 19761323
TI  - Assessing direction-specific adaptation using the steady-state visual evoked
      potential: results from EEG source imaging.
AB  - Studying directional selectivity using neuroimaging in humans is difficult
      because the resolution is insufficient to directly access directionally selective
      activity. Here we used motion adaptation of the steady-state visual evoked
      potential (SSVEP) and source imaging in the frequency domain to detect brain
      areas that contain direction-selective cells. This study uses a definitive
      electrophysiological marker for direction-specific adaptation in the SSVEP to
      localize cortical areas that are direction selective. It has been shown
      previously that an oscillating stimulus produces an SSVEP response that is
      dominated by even harmonics of the stimulus frequency. This pattern of response
      is consistent with equal population responses to each direction of motion.
      Prolonged exposure to unidirectional motion induces an asymmetry in the
      population response that is consistent with adaptation of direction-selective
      cells. This asymmetry manifests itself in the presence of odd harmonic components
      after adaptation Critically, the feature that indicates the direction used for
      adaptation is the phase of the odd-harmonic responses. We recorded this signature
      of direction selectivity in a group of observers whose retinotopic visual areas
      had been defined from fMRI mapping. We find direction-specific responses
      throughout retinotopic cortex, with the largest effect in areas V1 (occipital
      pole) and V3/V3a (dorsal).

PMID- 19761324
TI  - Effects of target enhancement and distractor suppression on multiple object
      tracking capacity.
AB  - Mounting evidence suggests that visual attention may be simultaneously deployed
      to multiple distinct object locations, but the constraints upon this multi-object
      attentional system are still debated. Results from multiple object tracking (MOT)
      experiments have been interpreted as revealing a fixed attentional capacity limit
      of 4 objects, while other evidence has suggested that attentional capacity may be
      more fluid. Here, we investigated the influence of target stimulus factors, such
      as speed and size, and of distractor filtering factors, such as number of
      distractors and screen density, on MOT performance. Each factor had significant
      effects on capacity, producing values that ranged from above 6 objects down to
      one object, depending on the task demands. Although our results support the view
      that crowding effects modulate the effective capacity of attention, we also find
      evidence that central processes related to distractor suppression and target
      enhancement modulate capacity.

PMID- 19761325
TI  - Pupil dynamics during bistable motion perception.
AB  - Pupil size not only varies to changes in illumination but is also modulated by
      several cognitive factors, making it a potentially versatile physiological marker
      of cortical states. We recorded pupil dynamics while subjects continuously
      reported their bistable perception of ambiguous moving stimuli, plaids, and
      partially occluded rotating diamonds. We observed small (about 5% of surface
      change on average) but reliable pupil dilation around (-300 ms to 1.5 s) the
      button presses indicating the changes of percepts. We found that 70% of pupil
      dilation could be accounted for by the motor response. The remaining perceptual
      component was similar for spontaneously occurring transitions and transitions
      triggered by physical stimulus manipulations. Moreover, the amplitude of pupil
      modulation in the spontaneous condition was unrelated to the duration of each
      perceptual state. It is therefore unlikely that the mechanisms of endogenous
      perceptual bistability reflect in the pupil. In addition, we measured a clear
      constriction of the pupil after blinks (about 8% of surface change on average).
      As pupil changes have the potential to entail retino-cortical activity, their
      monitoring in studies of visual processing could prove worthwhile.

PMID- 19761326
TI  - Higher-order aberrations produce orientation-specific notches in the defocused
      contrast sensitivity function.
AB  - Local minima or notches in the defocused contrast sensitivity function (CSF) have
      been linked to the aberrations of the eye. We use theoretical modeling of the
      effects of the aberrations to show these notches can be orientation-selective due
      to the effects of aberration terms such as coma and trefoil. Notches that changed
      with orientation were observed in the defocused CSF of four subjects. The
      measured CSFs were found to match well with theoretical predictions produced
      using the individual aberrations. Theoretical modeling highlighted orientation
      specific differences in notches for both positive and negative blur. The results
      indicate that orientation is an important variable when testing for the
      functional effects of higher-order aberrations.

PMID- 19761327
TI  - Experimental validation of a Bayesian model of visual acuity.
AB  - Based on standard procedures used in optometry clinics, we compare measurements
      of visual acuity for 10 subjects (11 eyes tested) in the presence of natural
      ocular aberrations and different degrees of induced defocus, with the predictions
      given by a Bayesian model customized with aberrometric data of the eye. The
      absolute predictions of the model, without any adjustment, show good agreement
      with the experimental data, in terms of correlation and absolute error. The
      efficiency of the model is discussed in comparison with image quality metrics and
      other customized visual process models. An analysis of the importance and
      customization of each stage of the model is also given; it stresses the potential
      high predictive power from precise modeling of ocular and neural transfer
      functions.

PMID- 19761328
TI  - Spatial contrast sensitivity and grating acuity of barn owls.
AB  - The eyes of barn owls (Tyto alba pratincola) display very little aberrations, and
      have thus excellent optical quality. In a series of behavioral experiments, we
      tested whether this presumably beneficial feature is also reflected at a
      perceptual level in this species. As fundamental indicators for visual
      performance, the spatial contrast sensitivity function (CSF) and grating acuity
      were measured in two barn owls with psychophysical techniques. Stimulus luminance
      was 2.7 cd/m(2). The CSF found here renders the typical band-limited, inverted U
      shaped function, with a low maximum contrast sensitivity of 8-19 at a spatial
      frequency of 1 cyc/deg. Grating acuity was estimated from the CSF high frequency
      cut-off and yielded 3.0-3.7 cyc/deg. In a second experiment, in which contrast
      was held constant and spatial frequency was varied, grating acuity was measured
      directly (2.6-4.0 cyc/deg). These results put barn owls at the very low end of
      the visual acuity spectrum of birds, and demonstrate that visual resolution and
      sensitivity cannot be predicted by optical considerations alone.

PMID- 19761329
TI  - Perceived duration of visual motion increases with speed.
AB  - Despite wide recognition that a moving object is perceived to last longer,
      scientists do not yet agree as to how this illusion occurs. In the present study,
      we conducted two experiments using two experimental methods, namely duration
      matching and reproduction, and systematically manipulated the temporal frequency,
      spatial frequency, and speed of the stimulus, to identify the determinant factor
      of the illusion. Our results indicated that the speed of the stimulus, rather
      than temporal frequency or spatial frequency per se, best described the perceived
      duration of a moving stimulus, with the apparent duration proportionally
      increasing with log speed (Experiments 1 and 2). However, in an additional
      experiment, we found little or no change in onset and offset reaction times for
      moving stimuli (Experiment 3). Arguing that speed information is made explicit in
      higher stages of visual information processing in the brain, we suggest that this
      illusion is primarily mediated by higher level motion processing stages in the
      dorsal pathway.

PMID- 19761330
TI  - A neurophysiologically plausible population code model for human contrast
      discrimination.
AB  - The pedestal effect is the improvement in the detectability of a sinusoidal
      grating in the presence of another grating of the same orientation, spatial
      frequency, and phase-usually called the pedestal. Recent evidence has
      demonstrated that the pedestal effect is differently modified by spectrally flat
      and notch-filtered noise: The pedestal effect is reduced in flat noise but
      virtually disappears in the presence of notched noise (G. B. Henning & F. A.
      Wichmann, 2007). Here we consider a network consisting of units whose contrast
      response functions resemble those of the cortical cells believed to underlie
      human pattern vision and demonstrate that, when the outputs of multiple units are
      combined by simple weighted summation-a heuristic decision rule that resembles
      optimal information combination and produces a contrast-dependent weighting
      profile-the network produces contrast-discrimination data consistent with
      psychophysical observations: The pedestal effect is present without noise,
      reduced in broadband noise, but almost disappears in notched noise. These
      findings follow naturally from the normalization model of simple cells in primary
      visual cortex, followed by response-based pooling, and suggest that in processing
      even low-contrast sinusoidal gratings, the visual system may combine information
      across neurons tuned to different spatial frequencies and orientations.

PMID- 19761331
TI  - Learning to attend: effects of practice on information selection.
AB  - Though practice can lead to improved performance in many domains, it is currently
      unknown how practice affects the deployment of selective attention to filter
      distracting information. We conducted a series of experiments to address this
      issue by examining how performance on a task changed after repeated exposure to
      distractors. Distraction initially slowed response time during task performance,
      an effect that diminished with repeated exposure to the distractors. When the
      distractors were consistent in appearance, the practice effect developed quickly
      but was stimulus-specific. When the distractors were more variable in appearance,
      the practice effect developed slowly but transferred more readily to other
      conditions. These data indicate that practice with overcoming distraction leads
      to improvements in information filtering mechanisms that generalize beyond the
      training regimen when variable distractor stimuli are experienced.

PMID- 19761332
TI  - Storing fine detailed information in visual working memory--evidence from event
      related potentials.
AB  - Visual working memory (VWM) maintains and manipulates a limited set of visual
      objects being actively used in visual processing. To explore whether and how the
      fine detailed information is stored in VWM, four experiments have been conducted
      while recording the contralateral delay activity (CDA), an event-related
      potential difference wave that reflects the information maintenance in VWM. The
      type of the remembered information was manipulated by adopting simple objects and
      complex objects as materials. We found the amplitude of CDA was modulated by
      object complexity: as the set size of memory array rose from 2 to 4, the
      amplitude of CDA stopped increasing for maintaining complex objects with detailed
      information, while continued increasing for storing highly discriminable simple
      objects. These results suggest that VWM can store the fine detailed information;
      however it can not store all the fine detailed information from 4 complex
      objects. It implies that the capacity of VWM is not only characterized by a fixed
      number of objects, there is at least one stage influenced by the detailed
      information contained in the objects. These results are further discussed within
      a two-stage storing model of VWM: different types of perceptual information
      (highly discriminable features and fine detailed features) are maintained in VWM
      via two distinctive mechanisms.

PMID- 19761333
TI  - Age-related decline of contrast sensitivity for second-order stimuli: earlier
      onset, but slower progression, than for first-order stimuli.
AB  - Many visual functions are known to decline during aging (P. D. Spear, 1993).
      However there has been no clear description as to how contrast sensitivity for
      second-order stimuli changes across the adult life span. Based on different
      mechanisms underlying perception of first-/second-order stimuli (Z. L. Lu & G.
      Sperling, 2001), and J. Faubert's (2002) theory of visual perception and aging,
      it is expected that perception of these two types of stimuli will change in
      different ways during aging. In this study we have measured contrast sensitivity
      for both first- and second-order stimuli in 141 subjects aged from 19 to 79 years
      old. The results have shown no gender effect but an evident aging effect, i.e., a
      progressive decline during aging, for perception of both types of stimuli. We
      have also proposed a piecewise linear model to interpret our data. Based on this
      model, contrast sensitivity for second-order stimuli begins to decline
      significantly earlier than for first-order stimuli, but with a slower rate of
      progression. We suggest the earlier decline for perception of second-order
      stimuli may be interpreted as reflecting a greater complexity of second-order
      processing.

PMID- 19761334
TI  - Looking ahead: the perceived direction of gaze shifts before the eyes move.
AB  - How do we know where we are looking? Our direction of gaze is commonly thought to
      be assigned to the location in the world that falls on our fovea, but this may
      not always hold, especially, as we report here, just before an eye movement.
      Observers shifted their gaze to a clock with a fast-moving hand and reported the
      time perceived to be on the clock when their eyes first landed. The reported time
      was 39 ms earlier than the actual time the eyes arrived. In a control condition,
      the clock moved to the eyes, mimicking the retinal motion but without the eye
      movement. Here the reported time lagged 27 ms behind the actual time on the clock
      when it arrived. The timing of perceived fixation in our experiment is similar to
      that for the predictive activation observed in visual cortex neurons at the time
      of eye movements.

PMID- 19761335
TI  - Ventral extra-striate cortical areas are required for human visual texture
      segmentation.
AB  - A patient (HJA) with bilateral occipital lobe damage to ventral cortical areas
      V2, V3 and V4 was tested on a texture segmentation task involving texture bar
      detection in an array of oriented lines. Performance detecting a target shape was
      assessed as the orientations of the background lines had increasing orientation
      noise. Control participants found the task easier when the background lines had
      the same orientation or only slightly shifted in orientation. HJA was poor with
      all backgrounds but particularly so when the background lines had the same or
      almost the same orientations. The results suggest that V1 alone is not sufficient
      to perform easy texture segmentation, even when the background of the display is
      a homogeneous texture. Ventral extra-striate cortical areas are needed in order
      to detect texture boundaries. We suggest that extra-striate visual areas enhance
      the borders between the target and background, while also playing a role in
      reducing the signal from homogeneous texture backgrounds.

PMID- 19761336
TI  - Congruency effects in the remote distractor paradigm: evidence for top-down
      modulation.
AB  - In three experiments, we examined effects of target-distractor similarity in the
      remote distractor effect (RDE). Observers made saccades to peripheral targets
      that were either gray or green. Foveal or peripheral distractors were presented
      at the same time. The distractors could either share the target's defining
      property (congruent) or be different from the target (incongruent). Congruent
      distractors slowed down saccadic reaction times more than incongruent
      distractors. The increase of the RDE with target-distractor congruency depended
      on task demands. The more participants had to rely on the target property to
      locate the target, the larger the congruency effect. We conclude that the RDE can
      be modulated in a top-down manner. Alternative explanations such as persisting
      memory traces for the target property or differences in stimulus arrangement were
      considered but discarded. Our claim is in line with models of saccade generation
      which assume that the structures underlying the RDE (e.g. the superior
      colliculus) receive bottom-up as well as top-down information.

PMID- 19761337
TI  - Scale dependence and channel switching in letter identification.
AB  - Letters are broadband visual stimuli with information useful for discrimination
      over a wide range of spatial frequencies. Yet, recent evidence suggests that
      observers use only a single, fixed spatial-frequency channel to identify letters
      and that the scale of that channel, in units of letter size, is determined by the
      size of the letter (scale dependence). We report two letter-identification
      experiments using critical-band masking. With sufficiently high-amplitude, low-
      or high-pass masking noise, observers switched to a different range of spatial
      frequencies for the task. Thus, letter channels are not fixed for a given letter
      size. When an additional white-noise masker was added to the stimulus to flatten
      the contrast-sensitivity function, the letter channel used by the observer still
      depended on letter size, further supporting the hypothesis that letter
      identification is scale dependent.

PMID- 19761338
TI  - Demonstration of an eye-movement-induced visual motion illusion (Filehne
      illusion) in Rhesus monkeys.
AB  - During pursuit eye movements, the world around us remains perceptually stable
      despite the retinal-image slip induced by the eye movement. It is commonly held
      that this perceptual invariance is achieved by subtracting an internal reference
      signal, reflecting the eye movement, from the retinal motion signal. However, if
      the reference signal is too small or too large, a false eye-movement-induced
      motion of the external world, the Filehne illusion (FI), will be perceived. A
      reference signal of inadequate size can be simulated experimentally by asking
      human subjects to pursue a target across backgrounds with externally added motion
      that are perceived as moving. In the present study we asked if non-human primates
      respond to such manipulation in a way comparable to humans. Using psychophysical
      methods, we demonstrate that Rhesus monkeys do indeed experience a percept of
      pursuit-induced background motion. In this study we show that an FI can be
      predictably induced in Rhesus monkeys. The monkey FI shows dependencies on the
      size and direction of background movement, which is very similar to the ones
      characterizing the human FI. This congruence suggests that the perception of self
      induced visual motion is based on similar inferential mechanisms in non-human and
      human primates.

PMID- 19761339
TI  - Different masking effects on "hole" and "no-hole" figures.
AB  - Global information is considered the primitive of visual perception in Gestalt
      psychology. Further, L. Chen (2005) proposed a new theory of topological visual
      perception. According to this theory, the perception of topological difference is
      faster than other feature differences. However, it is still not clear why
      topological perception has the priority. Based on previous studies, we
      hypothesize that it is caused by the different perception between figures with
      "hole" and figures without "hole" in the primitive of vision. In the present
      paper, four behavioral experiments and one ERP experiment were presented. Four
      behavioral experiments utilizing backward masking paradigm demonstrated that
      under the same masking effect, "hole" was easier perceived than "no hole". The
      ERP data may suggest that feedback connection in visual ventral pathway is
      disturbed by backward masking for "no-hole" stimuli, while it almost remains the
      same for "hole" stimuli. We suggest that temporal visual cortex is sensitive to
      "hole", thus facilitating the feedback connection to the occipital cortex. That
      is one of the reasons why topological perception is prior to local perception.

PMID- 19761340
TI  - On the nature of the stimulus information necessary for estimating mean size of
      visual arrays.
AB  - This paper explores the nature of the representations used for computing mean
      visual size of an array of visual objects of different sizes. In Experiment 1 we
      found that mean size judgments are accurately made even when the individual
      objects (circles) upon which those judgments were based were distributed between
      the two eyes. Mean size judgments were impaired, however, when a subset of the
      constituent objects involved in the estimation of mean size were rendered
      invisible by interocular suppression. These findings suggest that mean size is
      computed from relatively refined stimulus information represented at stages of
      visual processing beyond those involved in binocular combination and interocular
      suppression. In Experiment 2 we used an attentional blink paradigm to learn
      whether this refined information was susceptible to the constraints of attention.
      Accuracy of mean size judgments was unchanged when one of the two arrays of
      circles was presented within a rapid serial visual presentation sequence,
      regardless of task requirement (single vs. dual task) and the array's time of
      presentation relative to the brief appearance of a target that was the focus of
      attention. Evidently the refined stimulus information used for computing mean
      size remains available even in the absence of focused attention.

PMID- 19761341
TI  - Probabilistic combination of slant information: weighted averaging and robustness
      as optimal percepts.
AB  - Depth perception involves combining multiple, possibly conflicting, sensory
      measurements to estimate the 3D structure of the viewed scene. Previous work has
      shown that the perceptual system combines measurements using a statistically
      optimal weighted average. However, the system should only combine measurements
      when they come from the same source. We asked whether the brain avoids combining
      measurements when they differ from one another: that is, whether the system is
      robust to outliers. To do this, we investigated how two slant cues-binocular
      disparity and texture gradients-influence perceived slant as a function of the
      size of the conflict between the cues. When the conflict was small, we observed
      weighted averaging. When the conflict was large, we observed robust behavior:
      perceived slant was dictated solely by one cue, the other being rejected.
      Interestingly, the rejected cue was either disparity or texture, and was not
      necessarily the more variable cue. We modeled the data in a probabilistic
      framework, and showed that weighted averaging and robustness are predicted if the
      underlying likelihoods have heavier tails than Gaussians. We also asked whether
      observers had conscious access to the single-cue estimates when they exhibited
      robustness and found they did not, i.e. they completely fused despite the robust
      percepts.

PMID- 19761342
TI  - Visual motion aftereffects arise from a cascade of two isomorphic adaptation
      mechanisms.
AB  - Prolonged exposure to a moving stimulus can substantially alter the perceived
      velocity (both speed and direction) of subsequently presented stimuli. Here, we
      show that these changes can be parsimoniously explained with a model that
      combines the effects of two isomorphic adaptation mechanisms, one nondirectional
      and one directional. Each produces a pattern of velocity biases that serves as an
      observable "signature" of the corresponding mechanism. The net effect on
      perceived velocity is a superposition of these two signatures. By examining human
      velocity judgments in the context of different adaptor velocities, we are able to
      separate these two signatures. The model fits the data well, successfully
      predicts subjects' behavior in an additional experiment using a nondirectional
      adaptor, and is in agreement with a variety of previous experimental results. As
      such, the model provides a unifying explanation for the diversity of motion
      aftereffects.

PMID- 19761343
TI  - Maybe they are all circles: clues and cues.
AB  - When several cues provide information about the same property of a visual scene,
      a weighted average of the singe-cue estimates can provide a more reliable
      estimate than that of any individual cue. Some cues rely on assumptions about the
      scene, such as that shapes are isotropic. Assuming that an elliptical image
      arises from viewing a circle at an angle allows one to extract the circle's angle
      from the aspect ratio in the image. This study investigates whether the weight
      given to image shape as a slant cue depends on the prevailing circumstances.
      Neither rotating an object to provide direct evidence that it is circular, nor
      surrounding an object with circles rather than ellipses increased the weight
      assigned to image shape relative to that assigned to binocular information. Thus
      the weight given to slant cues does not seem to rely on an elaborate analysis of
      the scene.

PMID- 19761344
TI  - The discrimination of chromatic textures.
AB  - Color discrimination is influenced by chromatic distributions such as they appear
      on differently illuminated 3D surfaces (T. Hansen, M. Giesel, & K. R.
      Gegenfurtner, 2008). Here, we measured discrimination thresholds for
      chromatically variegated stimuli and modeled the data employing a model with
      multiple chromatic mechanisms. Each mechanism has a differently tuned half-wave
      rectified cosine-shaped sensitivity profile centered at a different chromatic
      direction. To estimate thresholds, the model's responses to a test and a
      comparison stimulus are determined. A detection variable is calculated by taking
      the difference of the responses to the two stimuli and by a subsequent nonlinear
      combination of the responses. The model was fitted to the data presented in T.
      Hansen et al. (2008) and to data from two new experiments. In the first
      experiment, we measured discrimination thresholds for stimuli chromatically
      variegated along a direction orthogonal to the one used in the previous
      experiments. In the second experiment, we investigated the interplay between
      chromatic distributions and different mean contrast levels. We found that a model
      with eight mechanisms accounted for the effect of chromatic variation within the
      stimuli and provided a better fit to the discrimination thresholds than a four
      mechanisms model.

PMID- 19761346
TI  - Anchoring of lightness values by relative luminance and relative area.
AB  - Surface lightness is widely thought to depend on the relative luminance coming
      from neighboring surfaces. But relative luminance can produce only relative
      lightness values. Specific lightness values can be derived only with an anchoring
      rule that specifies how relative luminance values in the retinal image are mapped
      onto the lightness scale. We explored the anchoring rules governing very simple
      images consisting of two adjacent surfaces that fill the entire visual field.
      These were painted onto the interior of a large hemisphere that surrounded the
      observer's head. Lighter and darker radial sectors of the same two shades of gray
      were painted onto nine such hemispheres, but with different relative areas. The
      region of highest luminance was always seen as white. The lightness of the darker
      sector depended on relative area, appearing lighter as the darker sector became
      larger, but this effect was stronger when the darker sector was larger than the
      lighter, a pattern of results shown to be consistent with over a dozen prior
      studies of relative area and lightness.

PMID- 19761345
TI  - The linearity and selectivity of neuronal responses in awake visual cortex.
AB  - Neurons in primary visual cortex (V1) are frequently classified based on their
      response linearity: the extent to which their visual responses to drifting
      gratings resemble a linear replica of the stimulus. This classification is
      supported by the finding that response linearity is bimodally distributed across
      neurons in area V1 of anesthetized animals. However, recent studies suggest that
      such bimodal distribution may not reflect two neuronal types but a nonlinear
      relationship between the membrane potential and the spike output. A main
      limitation of these previous studies is that they measured response linearity in
      anesthetized animals, where the distance between the neuronal membrane potential
      and the spike threshold is artificially increased by anesthesia. Here, we
      measured V1 response linearity in the awake brain and its correlation with the
      neuronal spontaneous firing rate, which is related to the distance between
      membrane potential and threshold. Our results demonstrate that response linearity
      is bimodally distributed in awake V1 but that it is poorly correlated with
      spontaneous firing rate. In contrast, the spontaneous firing rate is best
      correlated to the response selectivity and response latency to stimuli.

PMID- 19761347
TI  - Different hue coding underlying figure segregation and region detection tasks.
AB  - Figure segregation from its background is one of the important functions of color
      vision for our visual system because it is a preliminary to shape recognition.
      However, little is known about the chromatic mechanisms underlying figure
      segregation as opposed to those underlying mere color discrimination and
      detection. We investigated whether there are differences in color difference
      thresholds between a shape discrimination task (involving figure segregation) and
      a simple region detection task. In the shape discrimination task the observer
      discriminated the shapes of two figures, which could be segregated from their
      background on the basis of a color direction (hue) difference. In the region
      detection task the observer simply detected a square region against its
      background. Thresholds of color direction differences from a range of background
      color directions were measured for each task. In addition, we added saturation
      variation in one condition to investigate the involvement of the cone-opponent
      channels in those tasks. First, the results showed that the saturation variation
      increased the thresholds evenly for all background color directions. This
      suggests that higher-order color mechanisms rather than the early cone-opponent
      mechanisms are involved in both of the two tasks. Second, the shapes of the
      background color direction-threshold functions were different between the two
      tasks and these shape differences were consistent across all observers. This
      finding suggests that hue information may be encoded differently for shape
      discrimination and region detection. Furthermore, differences in spatial
      frequency components and in the requirement for orientation extraction rarely
      affected the shapes of the threshold functions in additional experiments,
      suggesting the possibility that hue encoding for shape discrimination differs
      from encoding for region detection at a late stage of form processing where local
      orientation signals are globally integrated.

PMID- 19761348
TI  - Perceptual learning of global pattern motion occurs on the basis of local motion.
AB  - Enhancement in perceptual learning of a visual stimulus can often be explained
      either by learning of integrated visual information that is processed in higher
      visual areas or by learning of component information that is processed in lower
      visual areas. It is not clear on which visual information perceptual learning is
      predominantly based. We examined whether perceptual learning of global pattern
      motion occurs on the basis of local or global motion as a result of performance
      improvement in detecting contraction (or expansion) in a display in which
      contracting (or expanding) dots slightly outnumbers expanding (or contracting)
      dots. We measured the degree of transfer of the learning effect by presenting
      test stimuli spatially shifted so that the region of the test stimuli partially
      overlapped the trained region. The results showed that the degree of transfer was
      entirely dependent on how similar local motion directions in the test stimuli are
      to those in the trained stimulus in the overlapping area, irrespective of whether
      a test stimulus contained the same global motion direction as the trained or not.
      These results indicate that perceptual learning at least in the present setting
      occurs on the basis of local motion signals.

PMID- 19761349
TI  - Spatial-frequency and contrast properties of reading in central and peripheral
      vision.
AB  - In this study, we examined the effects of contrast and spatial frequency on
      reading speed and compared these effects between the normal fovea and periphery.
      We found that when text contrast was low, reading speed demonstrated spatial
      frequency tuning properties, with a peak tuning frequency that partially scaled
      with print size. The spatial-frequency tuning disappeared when text contrast was
      100%. The spatial-frequency tuning and scaling properties for reading were
      largely similar between the fovea and the periphery, and closely matched those
      for letter identification. Just as for the task of letter identification, we
      showed through an ideal-observer analysis that the spatial-frequency properties
      for reading could be primarily accounted for by the physical properties of the
      word stimuli combined with human observers' contrast sensitivity functions.

PMID- 19761350
TI  - Temporal dynamics of saccadic distraction.
AB  - The saccadic distractor effect, in which irrelevant stimuli delay saccades to
      target stimuli, is a popular tool for investigating saccadic competition. Here,
      we outline the main components of a competition framework to account for the
      temporal dynamics of the distractor effect, inspired by race models of saccade
      generation. We first test a key prediction of this framework: the degree of
      interference should depend upon the degree of temporal overlap of target and
      distractor signals in the competition stage, which will vary systematically with
      the relative processing speeds of the competing visual signals. In agreement with
      this, we found that, when varying the contrast of distractor stimuli, the
      presentation delay between target and distractor that maximizes interference
      varies systematically for different target-distractor pairs, correlated with the
      difference in saccadic latency for the pair. Second, our data illustrate a
      crucial methodological point: when comparing the effect of different distractors,
      measuring at only one time-point (e.g. simultaneity, as most studies have done)
      can produce misleading and contradictory results. Thus, it is essential to take
      the temporal dynamics of the system into account. Lastly, the framework predicts
      that the optimal delay for the latency distractor effect is different from that
      maximizing error rate, and our data confirms this.

PMID- 19761351
TI  - Temporal constraints on conscious vision: on the ubiquitous nature of the
      attentional blink.
AB  - The attentional blink (AB) refers to the finding that observers often miss the
      second of two masked visual targets (T1 and T2, e.g., letters) appearing within
      200-500 ms. Although the presence of a T1 mask is thought to be required for this
      effect, we recently found that an AB deficit can be observed even in the absence
      of a T1 mask if T2 is shown very briefly and followed by a pattern mask (M. R.
      Nieuwenstein, M. C. Potter, & J. Theeuwes, 2009). Using such a sensitive T2 task,
      the present study sought to determine the minimum requirements for eliciting an
      AB deficit. To this end, we examined if the occurrence of an AB depends on T1
      exposure duration, the requirement to perform a task for T1, and awareness of T1.
      The results showed that an AB deficit occurs regardless of the presentation
      duration of T1, and regardless of whether there is a T1 task. A boundary
      condition for the occurrence of an AB was found in conscious awareness of T1.
      With a near-threshold detection task for T1, attention blinked when T1 was seen,
      but not when T1 was missed. Accordingly, we conclude that the minimum requirement
      for an AB deficit is T1 awareness.

PMID- 19761352
TI  - Resting membrane potential and Na+,K+-ATPase of rat fast and slow muscles during
      modeling of hypogravity.
AB  - Antiorthostatic hindlimb suspension (unloading) decreased the resting membrane
      potential (RMP) of skeletal muscle fibers in fast extensor digitorum longus (EDL)
      and slow soleus (SOL) muscle of the rat by about 10% within 7 days and more.
      Inactivation of the membrane Na+,K+-pump by ouabain brought about similar
      depolarization as unloading. The increased sodium permeability of the membrane
      was excluded as the major cause of this depolarization by experiments in which
      TRIS was substituted for Na+ in the medium. On the other hand, the decrease in
      the electrogenic participation of the Na+,K+-pump is apparently one of the causes
      of RMP decrease during hypogravity, in EDL muscle in particular.

PMID- 19761353
TI  - Lamivudine for the prevention of hepatitis B virus reactivation after high-dose
      chemotherapy and autologous hematopoietic stem cell transplantation for patients
      with advanced or relapsed non-Hodgkin's lymphoma single institution experience.
AB  - OBJECTIVE: Hepatitis B virus (HBV) reactivation is a well-known complication in
      cancer patients receiving cytotoxic chemotherapy, resulting in varying degrees of
      liver damage. The objective of this study was to investigate the efficacy of
      lamivudine for the prevention of HBV reactivation in non-Hodgkin's lymphoma (NHL)
      patients undergoing high-dose chemotherapy and autologous hematopoietic stem cell
      transplantation (AHSCT). RESEARCH DESIGN AND METHODS: Thirty-two patients with
      NHL who were HBV surface antigen (HBsAg)-positive were enrolled in this pilot
      study. They were divided into two groups: 20 patients received prophylactic oral
      lamivudine 100 mg/day before, and until at least 6 months after transplantation.
      The historical control group comprised 12 patients who received high-dose
      chemotherapy and AHSCT without lamivudine. The incidence and severity of
      hepatitis due to HBV reactivation, as well as other adverse clinical outcomes,
      were compared between the two groups. RESULTS: Most baseline clinical
      characteristics were similar in the two groups, except for HBV e-antigen (HBeAg)
      positive status (85% in the lamivudine group vs 33.3% in the control group, p =
      0.006) and the type of AHSCT. There was a lower incidence of hepatitis due to HBV
      reactivation in the lamivudine group than in the control group (10 vs 50%, p =
      0.030), less severe hepatitis (0 vs 25%, p = 0.009), and lower mortality (0 vs
      25%, p = 0.236). An HBV variant with tyrosine methionine aspartate aspartate
      (YMDD) mutation was detected in one patient in the lamivudine group (5%) after
      administration of lamivudine for 9 months. No significant adverse events were
      associated with the use of prophylactic lamivudine, and hematopoietic
      reconstitution was not affected by the intervention. CONCLUSIONS: Prophylactic
      lamivudine may reduce the incidence and severity of chemotherapy-related HBV
      reactivation and hepatitis-related mortality in HBsAg-positive NHL patients
      receiving high-dose chemotherapy and AHSCT. Additional randomized, multicenter
      trials are warranted.

PMID- 19761354
TI  - Locally advanced rectal cancer: from molecular profiling to clinical practice. A
      literature review: Part 2.
AB  - Colorectal cancer is the third most common cause of cancer deaths worldwide. The
      management of rectal cancer has undergone, and continues to undergo, significant
      evolutions. In the last two decades, new multimodality strategies have been
      developed. The ability to predict tumor response before treatment could
      significantly impact the selection of patients for preoperative combined-modality
      therapy, as well as potentially modify postoperative treatment plans. The present
      review analyzes the new molecular targets that could be involved in predicting
      response and prognosis.

PMID- 19761355
TI  - Breast cancer: beyond the cutting edge.
AB  - Remarkable progress has been made in the treatment of breast cancer over the past
      100 years. The ability to probe at the genomic level increased our understanding
      of the disease but the improved survival outcomes can also be attributed to
      screening programs, which have altered the pattern of diagnosis and prognosis,
      and to a number of groundbreaking clinical trials. Indeed, the latter are largely
      responsible for the most startling paradigm reversals in oncology; namely, that
      optimal benefit can be achieved with minimal, rather than maximal, intervention.
      As such, surgical lumpectomy can replace the radical mastectomy, sentinel node
      biopsy may circumvent the need for complete (axillary) nodal dissection, hormonal
      therapy--depending on tumor sensitivity to endocrine manipulation--is likely to
      be beneficial without the addition of chemotherapy, and some targeted therapies
      can be used selectively in those most likely to benefit. However, despite the
      advances, controversies remain; patients die; and cure remains elusive.

PMID- 19761356
TI  - The use of intraocular corticosteroids.
AB  - BACKGROUND: Diabetic macular edema (DME), cystoid macular edema (CME), age
      related macular degeneration (AMD), retinal vascular occlusion (RVO) and uveitis
      are responsible for severe visual impairment worldwide. In some patients with
      these conditions, treatment with intraocular corticosteroids may be beneficial.
      Although off-label use of these agents has occurred for many years, novel agents
      including preservative-free and sustained-release intravitreal implants are
      currently being studied in clinical trials (CTs). OBJECTIVE: To review the use of
      intraocular corticosteroids. METHODS: Literature review. RESULTS: Used alone,
      intravitreal corticosteroids may benefit disorders such as DME, RVO and uveitis
      compared with standard therapy or observation. Patients with AMD may benefit more
      from combination treatment with photodynamic therapy, intravitreal corticosteroid
      and intravitreal anti-VEGF injections. Intraoperative use of these agents may
      assist in visualization and manipulation of fine retinal structures. Sustained
      release intraocular implants have been approved for severe posterior uveitis, and
      have shown benefits in ongoing CTs. CONCLUSION: Although intraocular
      corticosteroid injections have a limited duration of action requiring frequent re
      treatment, and significant side effects including cataract and glaucoma
      development, intraocular injections may be of benefit in certain ocular
      disorders. Corticosteroid implants are emerging as potential treatments for
      macular edema due to uveitis, DME or RVO.

PMID- 19761357
TI  - Benzoyl peroxide: a review of its current use in the treatment of acne vulgaris.
AB  - BACKGROUND: Owing to the use of topical and systemic antibiotics for acne
      vulgaris, the incidence of antibiotic-resistant Propionibacterium acnes is
      increasing worldwide. Topical benzoyl peroxide (BPO) is an alternative to
      antibiotics in the treatment of acne vulgaris. OBJECTIVE: This review describes
      and evaluates recent clinical literature regarding the efficacy and tolerability
      of BPO. METHODS: A PubMed literature search was conducted using the keywords
      benzoyl peroxide, acne, and combination therapy. RESULTS: BPO is equally
      effective at concentrations of 2.5, 5.0 and 10%. However, a concentration
      dependent irritant dermatitis can occur with higher concentrations. The efficacy
      of BPO can be enhanced when used in combination with topical retinoids,
      antibiotics and tertiary amines. BPO-containing combinations do not induce
      bacterial resistance and are important first-line treatments for mild to moderate
      acne vulgaris.

PMID- 19761358
TI  - Pharmacokinetics and pharmacodynamics of insulin lispro protamine suspension
      compared with insulin glargine and insulin detemir in type 2 diabetes.
AB  - OBJECTIVE: The primary aim was to evaluate duration of action of a single 0.8
      U/kg dose of insulin lispro protamine suspension (ILPS) in type 2 diabetes (T2DM)
      patients; secondarily to compare onset and duration of action of ILPS, glargine
      (G), and detemir (D) (0.8 U/kg) and evaluate pharmacokinetic (PK) and
      pharmacodynamic (PD) dose responses of ILPS. RESEARCH DESIGN AND METHODS: In a
      single-center, double-blind, five-arm crossover study, 34 patients were
      randomized to a treatment sequence which included a single subcutaneous 0.8 U/kg
      dose of G and D and three doses of ILPS (0.4 U/kg, 0.8 U/kg, and 1.2 U/kg) and
      were studied using 24-hour euglycemic glucose clamps. PRIMARY OUTCOME MEASURE:
      Duration of action was determined as the time to the last measurable glucose
      infusion rate (tR(last)) during glucose clamps. RESULTS: The duration of insulin
      action (tR(last)) for ILPS at 0.8 U/kg was >23 hours and was similar to G (p =
      0.114) and D (p = 0.570). Post-hoc analysis demonstrated the probability of
      achieving 24 hours of glucose-lowering activity after a 0.8 U/kg dose: 48%
      (ILPS), 43% (G), and 26% (D). G(tot) and R(max) were significantly greater for
      ILPS versus G or D. The median ILPS time-dependent values demonstrated a
      significantly earlier maximum PD response (tR(max) and early 50% tR(max)) versus
      either G or D. ILPS demonstrated dose-dependent increases in PK and PD measures
      across the dose range. CONCLUSIONS: Following a single 0.8 U/kg dose in T2DM
      patients, ILPS, G, and D demonstrated similar durations of glucose-lowering
      activity and ILPS demonstrated significantly greater glucose-lowering activity
      (R(max) and G(tot)) and earlier maximum PD response. These results potentially
      support once-daily dosing of ILPS in T2DM. LIMITATIONS: The observed number of 24
      hour censored observations was higher than expected and the wash-out period for
      basal insulin treated patients may have been too short to definitively rule out a
      carry-over effect; however, such an effect, if present, would potentially only
      affect onset of action and not the primary outcome measure.

PMID- 19761360
TI  - Pharmacogenomics of ovulation induction: facilitating decisions on who, when and
      how to treat.

PMID- 19761363
TI  - Conference Scene: Pharmacogenomics at the second PharmSciFair 2009: adverse drug
      reactions and clinical implementation.
AB  - From 8th to 12th June 2009, the second PharmSciFair took place in Nice, France.
      Sessions were organized on different types of pharmaceutical research. Two
      pharmacogenomics sessions were organized by the European Federation for
      Pharmaceutical Sciences Network on Research in Pharmacogenetics/Pharmacogenomics.
      The topics of the sessions were adverse drug reactions and clinical
      implementation. Important conclusions of the presentations were that there has
      been much progress in the field of pharmacogenomics and that implementation in
      clinical practice is not as easy as it was once thought. Large prospective trials
      might be necessary to prove clinical relevance.

PMID- 19761364
TI  - Predicting response to short-acting bronchodilator medication using Bayesian
      networks.
AB  - AIMS: Bronchodilator response tests measure the effect of beta(2)-agonists, the
      most commonly used short-acting reliever drugs for asthma. We sought to relate
      candidate gene SNP data with bronchodilator response and measure the predictive
      accuracy of a model constructed with genetic variants. MATERIALS & METHODS:
      Bayesian networks, multivariate models that are able to account for simultaneous
      associations and interactions among variables, were used to create a predictive
      model of bronchodilator response using candidate gene SNP data from 308 Childhood
      Asthma Management Program Caucasian subjects. RESULTS: The model found that 15
      SNPs in 15 genes predict bronchodilator response with fair accuracy, as
      established by a fivefold cross-validation area under the receiver-operating
      characteristic curve of 0.75 (standard error: 0.03). CONCLUSION: Bayesian
      networks are an attractive approach to analyze large-scale pharmacogenetic SNP
      data because of their ability to automatically learn complex models that can be
      used for the prediction and discovery of novel biological hypotheses.

PMID- 19761365
TI  - Patterns of pharmacogenetic diversity in African populations: role of ancient and
      recent history.
AB  - AIMS: The knowledge that genetic variation influencing drug response is clearly
      structured among human populations has prompted many studies aimed at obtaining
      pharmacogenetic profiles in specific populations. While large amounts of data are
      being produced for populations from developed countries, the African continent
      still remains very poorly studied. To help to fill this gap, this work
      characterized three previously uncharacterized African populations for a set of
      pharmacogenetically relevant polymorphisms. MATERIALS & METHODS: Seven
      polymorphic variations in four genes that encode enzymes from phase I (CYP2C9,
      CYP3A4 and CYP3A5) or phase III (ABCB1) of drug metabolism were analyzed in
      population samples from Cabinda (n = 107), Mozambique (n = 109) and Sao Tome e
      Principe (n = 126). All three populations shared strong recent historical links
      with Portugal. RESULTS: The majority of the screened variations displayed large
      contrasts in allele frequencies between European and African populations, and
      this study identified a substantial higher European influence in Sao Tome e
      Principe than in Cabinda or Mozambique. Admixture analysis demonstrated that the
      European contribution to the population of Sao Tome e Principe amounted to 13.3
      +/- 3.3%. Furthermore, the proportion of African or European pharmacogenetic
      ancestry varied widely across each Sao Tomean individual. DISCUSSION &
      CONCLUSION: This implies that genetic association studies conducted in Sao Tome e
      Principe should take into account the confounding factor of admixture to avoid
      spurious positive or negative results. Our findings also indicate that drug
      dosage requirements may be different in Sao Tome e Principe than in other African
      populations. Thus, the search for pharmacogenetic risk factors should be assessed
      at an individual level, therefore fulfilling the perspective of personalized
      medicine. This study further indicates that the common notion of 'African
      population' might hide a pattern of pharmacogenetic heterogeneity whose real
      extent still needs to be evaluated by means of a refined sampling of the entire
      continent.

PMID- 19761366
TI  - Effects of genetic variation at the CYP2C19/CYP2C9 locus on pharmacokinetics of
      chlorcycloguanil in adult Gambians.
AB  - AIMS: Antimalarial biguanides are metabolized by CYP2C19, thus genetic variation
      at the CYP2C locus might affect pharmacokinetics and so treatment outcome for
      malaria. MATERIALS & METHODS: Polymorphisms in CYP2C19 and CYP2C9 in 43 adult
      Gambians treated with chlorproguanil/dapsone for uncomplicated malaria were
      assessed. Chlorcycloguanil pharmacokinetics were measured and associations with
      CYP2C19 and CYP2C9 alleles and CYP2C19 metabolizer groups investigated. RESULTS:
      All CYP2C19/CYP2C9 alleles obeyed Hardy-Weinberg equilibrium. There were 15
      CYP2C19/2C9 haplotypes with a common haplotype frequency of 0.23. Participants
      with the CYP2C19*17 allele had higher chlorcycloguanil area under the
      concentration versus curve at 24 h (AUC(0-24)) than those without (geometric
      means: 317 vs 216 ng.h/ml; ratio of geometric means: 1.46; 95% CI: 1.03 to 2.09;
      p = 0.0363) and higher C(max) (geometric mean ratio: 1.52; 95% CI: 1.13 to 2.05;
      p = 0.0071). CONCLUSION: CYP2C19*17 determines antimalarial biguanide metabolic
      profile at the CYP2C19/CYP2C9 locus.

PMID- 19761367
TI  - Genetic variations of NAT2 and CYP2E1 and isoniazid hepatotoxicity in a diverse
      population.
AB  - AIMS: TB is a serious global public health problem. Isoniazid, a key drug used to
      treat latent TB, can cause hepatotoxicity in some patients. This pilot study
      investigated the effects of genetic variation in NAT2 and CYP2E1 on isoniazid
      induced hepatotoxicity in TB contacts in British Columbia, Canada. MATERIALS &
      METHODS: DNA re-sequencing was used to establish the spectrum of genetic
      variation in the exons, promoter and conserved regions of NAT2 in all subjects.
      For CYP2E1, the CYP2E1*1C polymorphism was genotyped by PCR-RFLP. Association
      tests of NAT2 variants and haplotypes, as well acetylator types were performed.
      RESULTS: We enrolled 170 subjects on isoniazid treatment (23 cases and 147
      controls). Systematic re-sequencing of NAT2 revealed 18 known and 10 novel
      variants. CONCLUSION: No single genetic variant of NAT2 and CYP2E1 showed a
      significant association with isoniazid-induced hepatotoxicity in this highly
      heterogeneous population. There was evidence of a trend for increasing
      hepatotoxicity risk across the rapid, intermediate and slow acetylator groups (p
      = 0.08).

PMID- 19761368
TI  - Flavin-containing monooxygenase 3 polymorphisms in 13 ethnic populations from
      Europe, East Asia and sub-Saharan Africa: frequency and linkage analysis.
AB  - AIMS: To investigate intra- and inter-ethnic differences in three widespread
      (E158K, V257M and E308G) and two African-specific (D132H and L360P) flavin
      containing monooxygenase 3 (FMO3) polymorphisms. MATERIALS & METHODS: Allele
      frequencies were determined by TaqMan allelic discrimination assay in 2152
      healthy volunteers from Europe (Swedes, Italians and Turks), East Asia (Japanese)
      and sub-Saharan Africa (nine ethnic groups covering eastern, southern and western
      regions), followed by haplotype and linkage analysis. RESULTS: Significant
      subpopulation differences (p < 0.001) in allele frequencies were found for E158K,
      V257M and E308G in Europeans and regional differences (p < 0.01) for D132H among
      Africans. No carrier of P360 was identified. Cis-linkage between G308 and K158
      was confirmed with the compound variant (K158/G308) being found in a high
      proportion (12.0-38.3%) of non-African subjects, but rarely (1.3%) among
      Africans. CONCLUSIONS: Distribution of functionally relevant FMO3 polymorphisms
      varies not only between ethnicities but also within. The K158/G308 variant may
      have potential clinical importance primarily in non-African populations due to
      its low prevalence in Africa.

PMID- 19761369
TI  - Molecular diversity at the CYP2D6 locus in healthy and schizophrenic southern
      Brazilians.
AB  - AIMS: The delineation of allele distribution and frequency is required to
      effectively translate pharmacogenetics to the clinic and given the paucity of
      CYP2D6 data in the Brazilian population, the purpose of this research was to
      characterize CYP2D6 alleles and genotype frequencies in Brazilians of European
      and African ancestries. Moreover, since it is suggested in the literature that
      CYP2D6 poor metabolism might be involved with susceptibility to schizophrenia, we
      included data from Brazilian schizophrenic patients to verify if CYP2D6 poor
      metabolism phenotypes are associated with susceptibility to schizophrenia.
      MATERIALS & METHODS: We investigated 24 CYP2D6 polymorphisms, gene deletions and
      gene multiplications in 179 healthy individuals from Brazil, 92 of European
      descent and 87 African Brazilians. CYP2D6 gene polymorphisms were genotyped by a
      MassARRAY SNP genotyping system. RESULTS: A total of 19 different alleles and
      five allele duplications were identified in African and European Brazilians. No
      significant differences in CYP2D6 allele function or poor metabolizer predicted
      phenotype frequencies were observed between healthy controls and schizophrenic
      patients, but the predicted metabolic phenotype distribution showed a significant
      higher frequency of intermediate metabolizers in African Brazilians than in
      European Brazilians (p = 0.001). CONCLUSIONS: CYP2D6 poor metabolizer genotype
      seems not to be a determining factor of schizophrenia susceptibility in
      Brazilians. The characterization of CYP2D6 variability will be very useful for
      future pharmacogenetic studies in the Brazilian population.

PMID- 19761370
TI  - Drug-induced liver injury: insights from genetic studies.
AB  - Drug-induced liver injury (DILI) is an increasing health problem and a challenge
      for physicians, regulatory bodies and the pharmaceutical industry, not only
      because of its potential severity and elusive pathogenesis but also because it is
      often inaccurately diagnosed, commonly missed entirely and more often not
      reported. The general view is that idiosyncratic DILI, which is not predictable
      whether based on the pharmacology of the drug or on the dose administered, is
      determined by the presence in the recipient of variants in, or expression of,
      genes coding for key metabolic pathways and/or the immune response, and the
      interaction of these genetic variants with environmental variables. Furthermore,
      idiosyncratic DILI is an example of a complex-trait disease with two or more
      susceptibility loci, as reflected by the frequency of genetic variants in the
      population often being higher than the occurrence of significant liver injury.
      Polymorphisms of bioactivation/toxification pathways via the CYP450 enzymes
      (Phase I), detoxification reactions (Phase II) and excretion/transport (Phase
      III), together with immunological factors that might determine DILI are reviewed.
      Challenges such as gene-trait association studies and whole-genome studies, and
      future approaches to the study of DILI are explored. Better knowledge of the
      candidate genes involved could provide further insight for the prospective
      identification of susceptible patients at risk of developing drug-induced
      hepatotoxicity, development of new diagnostic tools and new treatment strategies
      with safer drugs.

PMID- 19761371
TI  - Cytochrome P450 2C8 pharmacogenetics: a review of clinical studies.
AB  - Cytochrome P450 (CYP) 2C8 is responsible for the oxidative metabolism of many
      clinically available drugs from a diverse number of drug classes (e.g.,
      thiazolidinediones, meglitinides, NSAIDs, antimalarials and chemotherapeutic
      taxanes). The CYP2C8 enzyme is encoded by the CYP2C8 gene, and several common
      nonsynonymous polymorphisms (e.g., CYP2C8*2 and CYP2C8*3) exist in this gene. The
      CYP2C8*2 and *3 alleles have been associated in vitro with decreased metabolism
      of paclitaxel and arachidonic acid. Recently, the influence of CYP2C8
      polymorphisms on substrate disposition in humans has been investigated in a
      number of clinical pharmacogenetic studies. Contrary to in vitro data, clinical
      data suggest that the CYP2C8*3 allele is associated with increased metabolism of
      the CYP2C8 substrates, rosiglitazone, pioglitazone and repaglinide. However, the
      CYP2C8*3 allele has not been associated with paclitaxel pharmacokinetics in most
      clinical studies. Furthermore, clinical data regarding the impact of the CYP2C8*3
      allele on the disposition of NSAIDs are conflicting and no definitive conclusions
      can be made at this time. The purpose of this review is to highlight these
      clinical studies that have investigated the association between CYP2C8
      polymorphisms and CYP2C8 substrate pharmacokinetics and/or pharmacodynamics in
      humans. In this review, CYP2C8 clinical pharmacogenetic data are provided by drug
      class, followed by a discussion of the future of CYP2C8 clinical pharmacogenetic
      research.

PMID- 19761372
TI  - Sex-specific differences in side effects of psychotropic drugs: genes or gender?
AB  - Sex differences observed in the adverse effects associated with psychotropic
      drugs have not been reported consistently in the literature. In this review, we
      discuss the current published data on sex differences observed in the occurrence,
      symptomatology and reporting of the adverse effects associated with psychotropic
      drug effects, and discuss their clinical relevance. We reviewed the published
      data up to April 2009 on sex differences in the side effects of antipsychotics,
      antidepressant and mood stabilizers, by systematically searching PubMed using
      combinations of search terms and retrieving relevant references specifically
      reporting on these issues. The majority of the data was retrieved from clinical
      studies where the main outcome parameters did not relate specifically to sex
      differences. In most instances, sex was associated with other factors influencing
      side effects such as age, disease and body weight. Sex-related differences were
      reported in the side effects associated with antipsychotic drug-induced weight
      gain and metabolic syndrome, symptoms of sexual dysfunction caused by
      antidepressants and antipsychotic drugs and cardiac arrhythmic side effects
      associated with antipsychotic drugs. Women might differ from men not only in
      incidence but also in the presentation of clinical symptoms associated with
      adverse psychotropic drug effects. Clinicians should be made aware of the
      differences reported in the literature regarding the symptomatology, severity and
      recognition of the adverse psychotropic drug effects found in men and women.

PMID- 19761376
TI  - Spotlight on the future of scientific publication.

PMID- 19761373
TI  - Genetic polymorphisms associated with acute lung injury.
AB  - Acute lung injury and acute respiratory distress syndrome are the result of
      intense inflammation in the lungs leading to respiratory failure. The causes of
      acute lung injury/acute respiratory distress syndrome are numerous (e.g.,
      pneumonia, sepsis and trauma) but the reasons why certain individuals develop
      lung injury in response to these stimuli and others do not are not well
      understood. There is ample evidence in the literature that gene-host and gene
      environment interactions may play a large role in the morbidity and mortality
      associated with this syndrome. In this review, we initially discuss methods for
      identification of candidate acute lung injury/acute respiratory distress syndrome
      susceptibility genes using a number of model systems including in vitro cell
      systems and inbred mice. We then describe examples of polymorphisms in genes that
      have been associated with the pathogenesis of acute lung injury/acute respiratory
      distress syndrome in human case-control studies. Systematic bench to bedside
      approaches to understand the genetic contribution to acute lung injury/acute
      respiratory distress syndrome have provided important insight to this complex
      disease and continuation of these investigations could lead to the development of
      novel prevention or intervention strategies.

PMID- 19761377
TI  - Gene mapping of 18S and 5S rDNA genes in the karyotype of the three-spot gourami
      Trichogaster trichopterus (Perciformes, Osphronemidae).
AB  - Ornamental fish culture is important as an economic activity and for biodiversity
      conservation as well. The species of the genus Trichogaster (Perciformes,
      Osphronemidae), popularly known as three-spot gourami, are among the several
      commercial species raised around the world. In the present work, eight specimens
      of Thrichogaster trichopterus from aquarium trade facilities were analyzed. The
      karyotype was composed of 23 pairs of subtelo/acrocentric chromosomes.
      Fluorescent in situ hybridization allowed identifying the 18S ribosomal gene at
      telomeric region on long arms of the largest acrocentric pair. On the other hand,
      the 5S rRNA gene is located at a proximal region on a pair of medium-sized
      chromosomes. Such information is extremely useful in face of the risks of
      introduction and the development of ornamental fish trade, once many fish species
      can be identified only by genetic studies.

PMID- 19761378
TI  - Effective polyethyleneimine-mediated gene transfer into zebrafish cells.
AB  - Polyethyleneimine (PEI) has been broadly studied as a leading nonviral gene
      delivery carrier because of its relatively high transfection efficiency in a wide
      range of cell types. Here, we report gene transfer in zebrafish cells (ZF4) using
      PEI as a gene carrier and lipofectamine as a control. Formations of PEI-DNA
      complexes were characterized by a series of measurements. The particle size of
      PEI-DNA complexes decreased from 274 to 132 nm, the surface charge gradually
      increased from -26 to 29 mV, and the cytotoxicity for zebrafish cells was
      observed with increasing proportion of PEI. Gel retardation assay showed that DNA
      was completely bound by PEI with a negative-to-positive charge ratio of 4. It was
      observed by transmission electron microscopy that the morphology of PEI-DNA
      complexes was spherical with smooth surfaces. Flow cytometry revealed that the
      optimum transfection efficiency (27%) mediated by PEI was obtained at an negative
      to-positive charge ratio of 8, which was higher than that with lipofectamine.
      Luciferase activity assay confirmed the increase in reporter gene expression
      probably due to a more efficient formation of complex between DNA and PEI than
      DNA and lipofectamine. In conclusion, our study demonstrates that PEI may be
      applied as an effective gene carrier to mediate gene transfer into zebrafish
      cells.

PMID- 19761379
TI  - Mu opioid receptor from the zebrafish exhibits functional characteristics as
      those of mammalian mu opioid receptor.
AB  - The functional characterization of the mu opioid receptor from the zebrafish
      (zfMOR) is reported here. After transfection in HEK-293 cell line, using both
      peptidergic and nonpeptidergic opioid ligands in the competition and saturation
      binding experiments, in addition to the functional assays of (35)S-GTPgammaS
      binding assays and intracellular 3'-5'-cyclic adenosine monophosphate (cAMP)
      level determinations, we demonstrate that zfMOR exhibits a pharmacological
      profile similar to that of the mammalian MOR. Besides, the internalization
      process of zfMOR after opiate agonist treatment (morphine, DAMGO, etorphine)
      resembles the pattern observed for its mammalian counterpart. These similarities
      suggest that the zebrafish is a good model for the study of the opioid effects in
      development.

PMID- 19761380
TI  - Germplasm cryobanking in zebrafish and other aquarium model species.
AB  - During the last few years zebrafish and other aquarium fish have become more
      important model system species. In zebrafish valuable biotechnological lines are
      constantly emerging, and the creation of cryobanks of viable fish sperm, oocytes,
      and embryos from those lines is a constant and important demand. Cryopreservation
      is an essential tool for storing specific genetic material and would
      significantly help in the conservation of such lines, facilitating daily
      procedures in labs and companies working with this species. In this review, all
      advances achieved in this field are presented. Protocols for sperm
      cryopreservation are described, and the new directions of approaches in embryo
      and oocyte cryopreservation and also in blastomeres, and primordial germ cell
      cryopreservation are discussed.

PMID- 19761385
TI  - Neurometabolic changes in the acute phase after sports concussions correlate with
      symptom severity.
AB  - Sports concussion is a major problem that affects thousands of people in North
      America every year. Despite negative neuroimaging findings, many athletes display
      neurophysiological alterations and post-concussion symptoms such as headaches and
      sensitivity to light and noise. It is suspected that neurometabolic changes may
      underlie these changes. In this study we investigated the effects of sports
      concussion on brain metabolism using (1)H-MR spectroscopy by comparing a group of
      12 non-concussed athletes with a group of 12 concussed athletes of the same age
      (mean 22.5 years) and education (mean 16 years). All athletes were scanned 1-6
      days post-concussion in a 3T Siemens MRI, and were administered a symptom scale
      to evaluate post-concussion symptomatology. Participants also completed a
      neuropsychological test battery to assess verbal memory, visual memory,
      information processing speed, and reaction time, and no group differences were
      detected relative to controls. Concussed athletes showed a higher number of
      symptoms than non-concussed athletes, and they also showed a significant decrease
      in glutamate in the primary motor cortex (M1), as well as significant decreases
      in N-acetylaspartate in the prefrontal and primary motor cortices. No changes
      were observed in the hippocampus. Furthermore, the metabolic changes in M1
      correlated with self-reported symptom severity despite equivalent
      neuropsychological performance. These results confirm cortical neurometabolic
      changes in the acute post-concussion phase, and demonstrate for the first time a
      correlation between subjective self-reported symptoms and objective physical
      changes that may be related to increased vulnerability of the concussed brain.

PMID- 19761386
TI  - Bioaesthetics and regenerative medicine.

PMID- 19761387
TI  - Launching intravenous bone marrow cell trials for acute stroke.

PMID- 19761390
TI  - Interview: Discussions on the development of human embryonic stem cell-based
      therapies.
AB  - Dr Jane Lebkowski joined Geron Corporation in 1998 and is currently Senior Vice
      President and Chief Scientific Officer of the Regenerative Medicine Division. Dr
      Lebkowski heads Geron's human embryonic stem cell program, and is responsible for
      all research, preclinical development, product development, manufacturing and
      clinical development activities. Prior to Geron, Dr Lebkowski was Vice President
      of Research and Development at Applied Immune Sciences. Following the acquisition
      of Applied Immune Sciences by Rhone Poulenc Rorer (RPR, currently Sanofi
      Aventis), Dr Lebkowski remained at RPR as Vice President of Discovery Research.
      During Dr Lebkowski's tenure at RPR, she coordinated preclinical investigations
      of gene-therapy approaches for treatment of cancer, cardiovascular disease and
      nervous system disorders, and directed vector formulations and delivery
      development. Dr Lebkowski received her PhD in Biochemistry from Princeton
      University in 1982, and completed a postdoctoral fellowship at the Department of
      Genetics, Stanford University (CA, USA) in 1986. Dr Lebkowski has published over
      70 peer-reviewed papers and has 12 issued US patents. Dr Lebkowski serves as the
      co-chair of the Industrial Committee of the International Society for Stem Cell
      Research and serves on the editorial boards of several scientific publications.

PMID- 19761392
TI  - Hair follicle neogenesis induced by cultured human scalp dermal papilla cells.
AB  - AIM: To develop a method by which human hair follicle dermal papilla (DP) cells
      can be expanded in vitro while preserving their hair-inductive potential for use
      in follicular cell implantation, a cellular therapy for the treatment of hair
      loss. MATERIALS & METHODS: DP cells were isolated from scalp hair follicles in
      biopsies from human donors. DP cell cultures were established under conditions
      that preserved their hair-inductive potential and allowed for significant
      expansion. The hair-inductive potential of cells cultured for approximately 36
      doublings was tested in an in vivo flap-graft model. In some experiments, DiI was
      used to label cells prior to grafting. RESULTS: Under the culture conditions
      developed, cultures established from numerous donors reproducibly resulted in an
      expansion that averaged approximately five population doublings per passage.
      Furthermore, the cells consistently induced hair formation in an in vivo graft
      assay. Grafted DP cells appeared in DP structures of newly formed hairs, as well
      as in the dermal sheath and in the dermis surrounding follicles. Induced hair
      follicles persisted and regrew after being plucked 11 months after grafting.
      CONCLUSION: A process for the propagation of human DP cells has been developed
      that provides significant expansion of cells and maintenance of their hair
      inductive capability, overcoming a major technical obstacle in the development of
      follicular cell implantation as a treatment for hair loss.

PMID- 19761393
TI  - Conjunctival epithelial cells maintain stem cell properties after long-term
      culture and cryopreservation.
AB  - AIM: Transplantation of tissue-engineered conjunctival epithelial cell sheets has
      proven to be a promising technique for conjunctival reconstruction. The ability
      to cryopreserve conjunctival epithelial cells and maintain their stem cell
      population would improve their availability for clinical use. The aim of this
      study was to evaluate whether cryopreservation and long-term in vitro culture has
      an effect on the proliferative capacity and the progenitor-like cell
      characteristics of conjunctival epithelial cells. METHOD: Human conjunctival
      cells from bulbar biopsies were isolated and expanded on a growth arrested 3T3
      feeder layer. The cells were evaluated for cytokeratin (CK4/CK19) expression by
      immunostaining. An aliquot with half of the cells from the initial culture was
      frozen in liquid nitrogen and stored for 14 days and, in addition, donor cells
      were cryopreserved for more than 6 months (202.7 +/- 13.0 days). Both
      cryopreserved and noncryopreserved cells were serially cultivated over four
      passages. For each passage the colony-forming efficiency and the cell population
      doubling rates were evaluated, and expression of putative progenitor cell
      markers, p63alpha and ABCG2, was assessed by immunostaining and reverse
      transcription PCR. RESULTS: Both noncryopreserved and cryopreserved cells
      demonstrated a high colony-forming capacity that decreased with passage. Cells
      from both groups underwent approximately 20 cell population doublings before
      senescence. Immunoreactivity to p63alpha and ABCG2 was found in both groups until
      passage 4 and their presence was also confirmed by reverse transcription PCR. No
      difference in cell viability, colony-forming efficiency and immunoreactivity to
      p63alpha and ABCG2 was observed between cells cryopreserved for 14 days, and more
      than 6 months (202.7 +/- 13.0 days). CONCLUSION: Conjunctival epithelial cells
      with progenitor cell-like characteristics can be efficiently cryopreserved and
      can subsequently maintain their function in vitro over several culture passages.
      The option to cryopreserve conjunctival cells prior to in vitro expansion would
      be an advantage when cells have to be cultivated for clinical transplantation.

PMID- 19761394
TI  - Ficoll-Paque versus Lymphoprep: a comparative study of two density gradient media
      for therapeutic bone marrow mononuclear cell preparations.
AB  - AIMS: Contradictory outcomes from recent clinical trials investigating the
      transplantation of autologous bone marrow mononuclear cell (BM-MNC) fraction
      containing stem/progenitor cells to damaged myocardium, following acute
      myocardial infarction, may be, in part, due to the different cell isolation
      protocols used. We compared total BM-MNC numbers and its cellular subsets
      obtained following isolation using Ficoll-Paque and Lymphoprep - two different
      density gradient media used in the clinical trials. MATERIALS & METHODS: Bone
      marrow samples were taken from patients entered into the REGENERATE-IHD clinical
      trial after 5 days of subcutaneous granulocyte colony-stimulating factor
      injections. Each sample was divided equally for BM-MNC isolation using Ficoll
      Paque and Lymphoprep, keeping all other procedural steps constant. Isolated
      fractions were characterized for hematopoietic stem cells, endothelial progenitor
      cells, T lymphocytes, B lymphocytes and NK cells using cell surface markers
      CD34(+), CD133(+)VEGFR2(+), CD45(+)CD3(+), CD45(+)CD19(+) and
      CD45(+)CD16(+)CD56(+), respectively. There were no significant differences in the
      absolute numbers and percentage cell recovery of various mononuclear cell types
      recovered following separation using either density gradient media. Cell
      viability and the proportion of various cell phenotypes investigated were similar
      between the two media. They were also equally efficient in excluding unwanted red
      blood cells, granulocytes and platelets from the final cell products. CONCLUSION:
      We demonstrated that the composition and quantity of cell types found within
      therapeutic BM-MNC preparations for use in clinical trials of cardiac stem cell
      transplantation are not influenced by the type of density gradient media used
      when comparing Ficoll-Paque and Lymphoprep.

PMID- 19761395
TI  - Pulp and dentin tissue engineering and regeneration: current progress.
AB  - Dental pulp tissue is vulnerable to infection. Entire pulp amputation followed by
      pulp-space disinfection and filling with an artificial rubber-like material is
      employed to treat the infection - commonly known as root-canal therapy.
      Regeneration of pulp tissue has been difficult as the tissue is encased in dentin
      without collateral blood supply except from the root apical end. However, with
      the advent of the concept of modern tissue engineering and the discovery of
      dental stem cells, regeneration of pulp and dentin has been tested. This article
      will review the early attempts to regenerate pulp tissue and the current endeavor
      of pulp and dentin tissue engineering, and regeneration. The prospective outcome
      of the current advancement in this line of research will be discussed.

PMID- 19761396
TI  - Intracoronary blood- or bone marrow-derived cell transplantation in patients with
      ischemic heart disease.
AB  - Soon after the first experimental scientific investigations of cell
      transplantation in various animal models of myocardial infarction and left
      ventricular dysfunction, a growing number of clinical trials evaluated the
      effects of intracoronary injection of peripheral blood- or bone marrow-derived
      cells in patients with myocardial infarction or chronic ischemic heart disease.
      In most of these trials, changes in parameters of left ventricular remodeling
      over time, such as left ventricular volumes, ejection fraction or infarct size,
      were used as trial end points, whereas information on mortality and morbidity
      after cell transplantation is sparse. Several meta-analyses, each including
      various sets of studies, estimated that intracoronary cell therapy was associated
      with small reductions in left ventricular end-systolic volumes and a moderate
      increase in left ventricular ejection fraction of 2.9-6.1% over time compared
      with control patients. As most of the clinical trials included a limited number
      of patients, results vary substantially between different studies. When
      evaluating whether effects of intracoronary cell transplantation on parameters of
      left ventricular remodeling may be transferable to meaningful consequences in
      terms of clinical outcome, the following aspects appear to be imperative. Robust
      data on mortality and clinical events based on a sufficient number of patients
      are required. Furthermore, effects of cell therapy must be compared with
      established therapeutic concepts for the treatment of myocardial infarction, such
      as reperfusion therapy or pharmacological interventions aiming at favorably
      influencing the remodeling process. Moreover, the potential effects of cell
      therapy must be evaluated as treatment options additive to established
      therapeutic strategies.

PMID- 19761397
TI  - Engineering microenvironments for embryonic stem cell differentiation to
      cardiomyocytes.
AB  - Embryonic stem cells and induced pluripotent stem cells have the potential to be
      a renewable source of cardiomyocytes for use in myocardial cell replacement
      strategies. Although progress has been made towards differentiating stem cells to
      specific cell lineages, the efficiency is often poor and the number of cells
      generated is not suitable for therapeutic usage. Recent studies demonstrated that
      controlling the stem cell microenvironment can influence differentiation.
      Components of the extracellular matrix are important physiological regulators and
      can provide mechanical cues, direct differentiation and improve cell engraftment
      into damaged tissue. Bioreactors are used to control the microenvironment and
      produce large numbers of desired cells. This article describes recent methods to
      achieve cardiomyocyte differentiation by engineering the stem cell
      microenvironment. Successful translation of stem cell research to therapeutic
      applications will need to address large-scale cardiomyocyte differentiation and
      purification, assessment of cardiac function and synchronization, and safety
      concerns.

PMID- 19761398
TI  - Microencapsulated stem cells for tissue repairing: implications in cell-based
      myocardial therapy.
AB  - Stem cells have the unique properties of self-renewal, pluripotency and a high
      proliferative capability, which contributes to a large biomass potential. Hence,
      these cells act as a useful source for acquiring renewable adult cell lines.
      This, in turn, acts as a potent therapeutic tool to treat various diseases
      related to the heart, liver and kidney, as well as neurodegenerative diseases
      such as Parkinson's and Alzheimer's disease. However, a major problem that must
      be overcome before it can be effectively implemented into the clinical setting is
      a suitable delivery system that can retain an optimal quantity of the cells at
      the targeted site for a maximal clinical benefit; a system that will give a
      mechanical as well as an immune protection to the foreign cells, while at the
      same time enhancing the yields of differentiated cells, maintaining cell
      microenvironments and sustaining the differentiated cell functions. To address
      this issue we opted for a novel delivery system, termed the 'artificial cells',
      which are semipermeable microcapsules with strong and thin multilayer membrane
      components with specific mass transport properties. Here, we briefly introduce
      the concept of artificial cells for encapsulation of stem cells and investigate
      the application of microencapsulation technology as an ideal tool for all stem
      transplantations and relate their role to the emerging field of cellular
      cardiomyoplasty.

PMID- 19761400
TI  - Induced pluripotent stem cells in regenerative medicine: an argument for
      continued research on human embryonic stem cells.
AB  - Human embryonic stem cells (ESCs) can be induced to differentiate into a wide
      range of tissues that soon could be used for therapeutic applications in
      regenerative medicine. Despite their developmental potential, sources used to
      generate human ESC lines raise serious ethical concerns, which recently prompted
      efforts to reprogram somatic cells back to a pluripotent state. These efforts
      resulted in the generation of induced pluripotent stem (iPS) cells that are
      functionally similar to ESCs. However, the genetic manipulations required to
      generate iPS cells may complicate their growth and developmental characteristics,
      which poses serious problems in predicting how they will behave when used for
      tissue-regenerative purposes. In this article we summarize the recently developed
      methodologies used to generate iPS cells, including those that minimize their
      genetic manipulation, and discuss several important complicating features of iPS
      cells that may compromise their future use for therapies in regenerative
      medicine.

PMID- 19761402
TI  - Differential inhibition of homotrimeric dUTPases by the 3'-azido derivative of
      dideoxy-UTP.
AB  - The inhibitory effects of 3'-azido-2',3'-dideoxyuridine-5'-triphosphate in
      complex with the Mg2+ ion (azido-ddUTP.Mg) on the dUTPases of the human, E. coli,
      and equine infectious anemia virus have been compared. Azido-ddUTP is analogous
      to drugs used in the treatment of HIV. Here it is shown to inhibit the bacterial
      dUTPase in a competitive manner (Ki = 9.3 microM), but to exhibit only marginal
      or no binding to the human and viral dUTPases, respectively. This is the first
      demonstration of an inhibitor with a strong preference for binding to a bacterial
      dUTPase over the human enzyme. The specific binding to the E. coli dUTPase is
      surprising in view of the close to identical substrate pockets among the three
      dUTPases tested. The results are discussed with reference to the possibility of
      designing active site directed inhibitors that bind to the homotrimeric dUTPase
      of a pathogen but not to the human form.

PMID- 19761399
TI  - Reclaiming a natural beauty: whole-organ engineering with natural extracellular
      materials.
AB  - The ability to engineer whole organs as replacements for allografts and
      xenografts is an ongoing pursuit in regenerative medicine. While challenges
      remain, including systemic tissue integration with angiogenesis, lymphatiogenesis
      and neurogenesis, ongoing efforts are working to develop novel technologies to
      produce implantable engineered scaffolds and potentially engineered whole organs.
      Natural extracellular matrix materials, commonly utilized in vitro, are now being
      used as effective, natural, acellular allografts, and are being integrated into
      nanoscale scaffolds and matrices with programmable responsiveness. Based on the
      significant use of natural scaffolds for tissue regeneration and bioengineering
      strategies, this review focuses on recent and ongoing efforts to engineer whole
      organs, such as the tooth, featuring natural extracellular matrix molecules.

PMID- 19761404
TI  - Human nasal mucosa contains tissue-resident immunologically responsive
      mesenchymal stromal cells.
AB  - Multipotent mesenchymal stromal cells (MSC) are present in bone marrow and other
      tissues such as adipose tissue, muscle, pancreas, liver, and so on. Recent
      evidence suggests that MSC migrate to sites of infection, inflammation, and
      cancer, and interact with different immune cell subsets. Here, we report for the
      first time on the isolation and characterization of multipotent nasal mucosa
      derived mesenchymal stromal cells (nm-MSC). nm-MSC showed a plastic adherent and
      fibroblast-like morphology and were able to form colonies. They expressed the
      typical bone marrow MSC marker antigens CD29, CD44, CD73, CD90, and CD105 and
      were able to differentiate along the adipogenic, chondrogenic, and osteogenic
      pathways. nm-MSC produced a set of inflammatory cytokines, expressed chemokine
      receptors, and were responsive to stimulation with cytokines, chemokines, and
      TLR4 ligand LPS. Thus, these cells may serve as an alternative adult stromal cell
      resource for regenerative tissue repair and may represent important regulators of
      local mucosal immunity.

PMID- 19761403
TI  - Gene expression in lung and liver after intravenous infusion of polyethylenimine
      complexes of Sleeping Beauty transposons.
AB  - Two methods of systemic gene delivery have been extensively explored, using the
      mouse as a model system: hydrodynamic delivery, wherein a DNA solution equivalent
      in volume to 10% of the mouse weight is injected intravenously in less than 10
      sec, and condensation of DNA with polyethylenimine (PEI) for standard intravenous
      infusion. Our goal in this study was to evaluate quantitatively the kinetics of
      gene expression, using these two methods for delivery of Sleeping Beauty
      transposons. Transposons carrying a luciferase expression cassette were injected
      into mice either hydrodynamically or after condensation with PEI at a PEI
      nitrogen-to-DNA phosphate ratio of 7. Gene expression in the lungs and liver
      after hydrodynamic delivery resulted in exponential decay with a half-life of
      about 35-40 hr between days 1 and 14 postinjection. The decay kinetics of gene
      expression after PEI-mediated gene delivery were more complex; an initial decay
      rate of 6 hr was followed by a more gradual loss of activity. Consequently, the
      liver became the primary site of gene expression about 4 days after injection of
      PEI-DNA, and by 14 days expression in the liver was 10-fold higher than in the
      lung. Overall levels of gene expression 2 weeks postinjection were 100- to 1000
      fold lower after PEI-mediated delivery compared with hydrodynamic injection.
      These results provide insight into the relative effectiveness and organ
      specificity of these two methods of nonviral gene delivery when coupled with the
      Sleeping Beauty transposon system.

PMID- 19761407
TI  - Prolyl hydroxylases and therapeutics.
AB  - Prolyl hydroxylases are members of the iron- and 2-oxoglutarate-dependent
      dioxygenase enzyme family. Collagen prolyl hydroxylase is well known for its
      involvement in scurvy, in which ascorbate deficiency inhibits the enzyme and
      results in characteristic signs of the disease. Several distinct prolyl
      hydroxylases that hydroxylate (and thereby regulate) the hypoxia-inducible factor
      (HIF) transcription factors were discovered in 2001. These HIF prolyl
      hydroxylases, termed prolyl hydroxylase domain enzymes (PHDs), are the subject of
      this forum. HIF coordinates the cellular response to hypoxia, and the PHDs have
      attracted widespread interest as potential therapeutic targets in a wide range of
      diseases including anemia, ischemic heart disease, stroke, cancer, and pulmonary
      hypertension. Novel PHD-based pharmaceutical agents are now undergoing clinical
      trials. As well as original data, this forum includes reviews discussing recent
      advances in the biochemistry and therapeutic manipulation of PHDs, the potential
      role of PHD inhibitors in neuroprotection, and the involvement of PHDs in the
      complex interaction between oxygen homeostasis and iron homeostasis.

PMID- 19761405
TI  - Activation of membrane NADPH oxidase associated with lysosome-targeted acid
      sphingomyelinase in coronary endothelial cells.
AB  - This study explored the mechanism mediating the aggregation of membrane NADPH
      oxidase (NOX) subunits and subsequent activation of this enzyme in bovine
      coronary arterial endothelial cells (CAECs). With confocal microscopy, we found
      that FasL stimulated lipid rafts (LRs) clustering with NOX subunit aggregation
      and acid sphingomyelinase (ASM) gathering, which was blocked by the siRNA of
      sortilin, an intracellular protein responsible for the binding and targeting of
      ASM to lysosomes. Correspondingly, FasL-induced O(2)(.-) production through NOX
      in LRs fractions was abolished by sortilin siRNA. Further, with flow-cytometry
      and fluorescence resonance energy transfer (FRET) analysis, we surprisingly
      demonstrated that after FasL stimulation, sortilin was exposed to cell membranes
      from lysosomes together with Lamp-1 and ASM, and these lysosomal components were
      aggregated and form a signaling complex in cell membranes. With co
      immunoprecipitation, lysosomal sortilin and ASM were found to interact more
      strongly when CAECs were stimulated by FasL. Functionally, inhibition of either
      sortilin expression, lysosome function, LRs clustering, or NOX activity
      significantly attenuated FasL-induced decrease in nitric oxide (NO) levels. It is
      concluded that lysosome-targeted ASM, through sortilin, is able to traffic to and
      expose to cell-membrane surface, which may lead to LRs clustering and NOX
      activation in CAECs.

PMID- 19761408
TI  - Invasive Haemophilus influenzae disease caused by non-type b strains in
      Northwestern Ontario, Canada, 2002-2008.
AB  - A high incidence of invasive non-type b Haemophilus influenzae disease was found
      in Northwestern Ontario, Canada; H. influenzae type a was the most prevalent
      serotype (42%). Clinical and demographic analyses indicate that aboriginal
      children aged <5 years and adults with predisposing medical conditions are the
      most affected by invasive H. influenzae disease in the post-H. influenzae vaccine
      era.

PMID- 19761409
TI  - Determination of group a streptococcal anti-M type-specific antibody in sera of
      rheumatic fever patients after 45 years.
AB  - Group A streptococcal M type--specific protective antibodies-especially their
      persistence in humans--are incompletely understood. Such information is essential
      for understanding the epidemiology and pathogenesis of these infections and their
      sequelae and is equally crucial for producing a group A streptococcal vaccine. We
      studied 2 adults for type-specific antibody 45 years after they experienced
      documented rheumatic fever.

PMID- 19761410
TI  - Development of herpes simplex virus stomatitis during receipt of cidofovir
      therapy.
AB  - We report 3 children who, after undergoing hematopoietic stem cell transplant,
      developed herpes simplex virus (HSV) stomatitis while receiving weekly cidofovir
      as preemptive treatment for cytomegalovirus infection. All patients responded
      well to treatment with either acyclovir or ganciclovir. Despite the in vitro
      susceptibility of HSV to cidofovir, once-weekly treatment with this agent may not
      be adequate prophylaxis in pediatric patients.

PMID- 19761411
TI  - Clinical experience in treating hypertension with fixed-dose combination therapy:
      angiotensin II receptor blocker losartan plus hydrochlorothiazide.
AB  - The goal of antihypertensive treatment is to reduce cardiovascular and
      cerebrovascular events associated with high blood pressure. A combination therapy
      with different antihypertensive agents is more successful than monotherapy in
      most hypertensive patients, with the added advantage of a better safety profile.
      Therefore, treatment of hypertensive patients with fixed-dose combination therapy
      consisting of the angiotensin II receptor blocker losartan along with
      hydrochlorothiazide (HCTZ) has several potential benefits over monotherapy with
      each individual component. It provides more effective blood pressure control, a
      reduction in the likelihood of adverse effects and facilitation of patient
      compliance due to a simple once-daily regimen. One of the advantages of the
      combination of losartan with HCTZ is the potential reduction in HCTZ-induced
      metabolic disorders; in particular, this combination can have attractive benefits
      for patients of hyperuricemia. Losartan plus HCTZ fixed-dose combination therapy
      is frequently recommended for the treatment of hypertension and lowers blood
      pressure in mild-to-moderate and even severe hypertensive patients to a level
      comparable with other classes of antihypertensive agents in combination with
      HCTZ. Fixed-dose combination therapy with losartan plus HCTZ is a logical choice
      as antihypertensive therapy for patients in whom combination therapy is necessary
      to achieve additional blood pressure reduction.

PMID- 19761412
TI  - Neridronic acid for the treatment of bone metabolic diseases.
AB  - Neridronic acid (6-amino-1-idroxyesilidene-1,1-bisphosphonate) is a nitrogen
      containing bisphosphonate licensed in Italy for the treatment of osteogenesis
      imperfecta and Paget's disease of bone. The pharmacodynamic profile is similar to
      that of other nitrogen-containing bisphosphonates and is characterized by its
      high affinity for bone tissue particularly at sites undergoing a process of
      remodeling. In growing children affected by osteogenesis imperfect, neridronic
      acid rapidly increases bone mineral density as measured by dual X-ray
      absortiometry and this is associated with a significant decrease in fracture
      cumulative number. Similar results have been obtained also in newborns (< 12
      month old) and in adult patients. In Paget's disease of bone, 200 mg intravenous
      neridronic acid is associated with a 65% rate of full remission and a biochemical
      response (decrease of > 75% of bone turnover markers) in 95% of the patients.
      Neridronic acid treatment has been reported to be effective also in other
      skeletal diseases such as osteoporosis, algodystrophy, hypercalcemia of
      malignancy and bone metastasis. Neridronic acid has been developed only for
      parenteral use, and it is the only one used as intramuscular injection. This
      avoids all the limitations of oral bisphosphonates and may be offered for a home
      treatment with simple nursing assistance.

PMID- 19761413
TI  - GnRH antagonist, cetrorelix, for pituitary suppression in modern, patient
      friendly assisted reproductive technology.
AB  - BACKGROUND: Gonadotropin-releasing hormone (GnRH) analogues are used routinely to
      prevent a premature luteinizing hormone (LH) surge in women undergoing assisted
      reproductive technology (ART) treatments. In contrast to GnRH agonists,
      antagonists produce rapid and reversible suppression of LH with no initial flare
      effect. OBJECTIVE: To review the role of cetrorelix, the first GnRH antagonist
      approved for the prevention of premature LH surges during controlled ovarian
      stimulation in modern ART. METHOD: A review of published literature on
      cetrorelix. RESULTS: Both multiple- and single-dose cetrorelix protocols were
      shown to be at least as effective as long GnRH agonist regimens for pituitary
      suppression in Phase II/III clinical trials. Furthermore, cetrorelix co-treatment
      resulted in similar live birth rates but a shorter duration of gonadotropin
      stimulation, a lower total gonadotropin dose requirement and lower incidence of
      ovarian hyperstimulation syndrome compared with long agonist regimens. A single
      dose cetrorelix protocol further decreased the number of injections required.
      Preliminary studies have also produced promising data on the use of cetrorelix in
      modified ART protocols, such as frozen embryo transfer and donor oocyte recipient
      cycles. CONCLUSION: Cetrorelix offers a potential therapeutic alternative to GnRH
      agonists during controlled ovarian stimulation and has become an integral part of
      modern, patient-friendly reproductive medicine.

PMID- 19761414
TI  - Quinaprilat: a review of its pharmacokinetics, pharmacodynamics, toxicological
      data and clinical application.
AB  - BACKGROUND: Quinaprilat is an ACE inhibitor for intravenous use especially in
      patients with arterial hypertension or chronic heart failure. In contrast to the
      oral prodrug quinapril, it has not been approved for clinical application.
      OBJECTIVE: In this review, the pharmacokinetic and pharmacodynamic profile of
      quinaprilat as well as toxicological data and results of preclinical and clinical
      studies are summarized. METHODS: In a PubMed search for the terms "quinaprilat"
      and "quinapril", literature relevant for this review was selected. RESULTS:
      Quinaprilat is a potent nonsulfhydryl selective ACE inhibitor with a short
      elimination half-life of 2 - 3 h, but due to slow dissociation from tissue ACE,
      once daily dosing is sufficient for effective ACE inhibition. Quinaprilat is
      excreted mainly in urine. In long-term animal studies, quinaprilat was not
      teratogenic, mutagenic or carcinogenic. However, due to the risk of fetal and
      neonatal morbidity and death, it should not be administrated in pregnancy.
      Quinaprilat is characterized by an excellent safety profile; adverse events occur
      infrequently and are rarely serious. CONCLUSION: Quinaprilat is an attractive ACE
      inhibitor, which potently inhibits tissue ACE.

PMID- 19761415
TI  - Chemokine receptor-related viral protein products.
AB  - Some Herpes-, Pox- and Irido-virus genes (and the controversial Stealth virus
      gene) share significant nucleotide sequences with vertebrate chemokine receptors
      (CKR) genes. In some instances the viral reading frame is the same as in the
      CKRs, giving rise to similar protein products. In other cases the reading frame
      is different and the viral protein product is not CKR-like. In yet other
      instances the segmental alignments between CKR genes and viral genes are more
      limited. In this article we discuss in detail only the more highly significant
      alignments. We propose the hypothesis that both CKR and CKR-like viral genes
      originated from a common ancestral gene. This older ancestor may have
      differentiated into two sequences, one giving rise to the group of extant CKR
      genes with relatively low levels of similarity with viruses, and the other to the
      other extant CKRs and the CKR-like viral products. The two extant proteins of the
      CKR and viral groups which share the maximum amino acid identities are the human
      CCR3 and the E1 of the Equid herpes virus 2, with a continuous alignment coverage
      of 73% of the viral molecule. It is thus proposed that the ancestral sequence
      giving rise to both CKRs and CKR-like viral products may have been similar to the
      extant human CCR3 and E1 Equid herpes virus 2.

PMID- 19761417
TI  - Strategies for short hairpin RNA delivery in cancer gene therapy.
AB  - RNA interference (RNAi) gene silencing can be achieved by delivering vectors that
      transcribe short hairpin RNA (shRNA), which stably express small interfering RNA
      in target cells. Therefore, shRNA is of potential therapeutic use for inhibiting
      cancer cells, in which aberrant expression of certain mRNA's causes problems.
      However, this technique has not yet been developed for cancer therapy. The major
      problem for clinical use is lack of effective methods of delivery. In this
      article, we review the current strategies for shRNA delivery for target
      validation and their therapeutic uses in cancer to help further the understanding
      of challenges confronting shRNA technology, such as different principles of RNAi
      technology, basic construction of shRNA-expressing vectors and delivery barriers,
      which exist for both local and systemic delivery stratiges. Even if there are
      data showing that shRNA can be used in mice, we are still a long way from its
      application in human cancer therapy, because serious problems remain, including
      biodistribution and clearance of nanoparticles following systemic delivery of
      shRNA-expressing vectors.

PMID- 19761418
TI  - VEGF as an inhibitor of tumor vessel maturation: implications for cancer therapy.
AB  - Tumor angiogenesis is an important component of cancer biology driven in part by
      the thesis that inhibition of tumor vessel growth would be expected to starve and
      thereby disrupt tumor growth. A significant portion of research on tumor
      angiogenesis has focused on VEGF and its blockade with the expectation that
      dramatic results would be demonstrated in cancer patients as previously
      documented in animal models. However, to date, anti-VEGF (bevacizumab, Avastin)
      therapy alone has demonstrated little if any antitumor activity or survival
      benefit in humans. Interestingly, bevacizumab in combination with
      chemotherapeutic agents appears to result in a modest survival benefit in
      patients with various malignancies. This has prompted the re-evaluation of the
      biological effects resulting from VEGF blockade. Recent reports indicate that
      inhibition of VEGF and its receptor can have dramatic and unexpected effects on
      mural and perivascular cells in the tumor microenvironment, leading to vascular
      smooth muscle cell/pericyte activation and vessel normalization/maturation.
      Specifically, when VEGF levels in tumors are high, recent studies suggest that
      this leads to reduced responsiveness of the mural cell to the related growth
      factor, platelet-derived growth factor. This raises the possibility that in
      addition to the demonstrated anti-angiogenic effect of VEGF neutralization, mural
      cell recruitment and thus vascular maturation might be among the most critical
      activities of anti-VEGF agents. This review seeks to explore how VEGF blockade
      impacts tumor vascular maturation and considers its implications for cancer
      therapy.

PMID- 19761420
TI  - Individualizing therapy for oropharyngeal cancer patients.

PMID- 19761419
TI  - Strategies for the targeted delivery of therapeutics for osteosarcoma.
AB  - BACKGROUND: Conventional therapy for osteosarcoma has reached a plateau of 60 -
      70%, a 5-year survival rate that has changed little in two decades, highlighting
      the need for new approaches. OBJECTIVE: To review the alternative means of
      delivering effective therapy for osteosarcoma that reach beyond the central
      venous catheter. METHODS: Drawing on the author's own experiences providing care
      to high-risk osteosarcoma patients and reviewing the last two decades of
      literature describing sarcoma therapy, available information is summarized about
      potential osteosarcoma treatments that deliver therapy by a less conventional
      route. RESULTS/CONCLUSIONS: Intra-arterial chemotherapy has a limited impact on
      survival, but may help to achieve a better limb salvage. Intrapleural
      chemotherapy is important for managing malignant effusions. The development of
      inhalation therapies, treatments that target new bone formation such as
      bisphosphonates, chemically targeted radiation and antibody-based therapies all
      have potential to improve osteosarcoma therapy.

PMID- 19761421
TI  - Clinical and biological diversity of splenic marginal zone lymphoma.

PMID- 19761423
TI  - Pemetrexed for the treatment of non-small-cell lung cancer.
AB  - Pemetrexed is a novel multi-targeted antifolate that is used in the treatment of
      both malignant pleural mesothelioma and non-small-cell lung cancer (NSCLC). Lung
      cancer is the most common cancer in the world and NSCLC represents approximately
      80% of all lung cancers. Pemetrexed is the first NSCLC drug for which 'treatment
      by-histology' has been determined. This refers to the greater efficacy of
      pemetrexed in patients with advanced NSCLC other than of predominantly squamous
      cell histology. The advent of treatment-by-histology represents a significant
      step forward in the treatment of lung cancer, allowing physicians to tailor
      therapies to the individual patient. Ongoing trials aim to establish the place of
      pemetrexed in maintenance, in combination with other 'targeted agents', in
      adjuvant therapy in early NSCLC and in concurrent radio/chemotherapy.

PMID- 19761424
TI  - Clinical efficacy and safety of zoledronic acid in prostate and breast cancer.
AB  - The anti-estrogen treatment for hormone-sensitive breast cancer and the androgen
      deprivation therapy for prostate cancer can lead to the development of
      osteoporosis and bone fractures. Metastases associated with prostate and breast
      cancer can also occur in bone. Bisphosphonates are used in these types of bone
      dysfunction. Zoledronic acid is the most potent bisphosphonate. In osteoporosis,
      zoledronic acid inhibits bone reabsorption and increases bone mineral density for
      at least a year after intravenous administration. The efficacy and safety of
      zoledronic acid in osteoporosis secondary to hormone-sensitive cancers (prostate
      and breast), and in the bone metastases associated with these cancers are
      reviewed.

PMID- 19761425
TI  - Personalizing cancer care: updates on head and neck cancer.
AB  - With an emphasis on personalizing cancer care, the American Society of Clinical
      Oncology 45th Annual Meeting was held from 29 May to 2 June in Orlando (FL, USA).
      Several abstracts were presented that will significantly impact the management of
      squamous cell carcinoma of the head and neck both currently and in the near
      future, especially with respect to patient selection for specific therapies,
      prognostic biomarkers and novel agents.

PMID- 19761426
TI  - Personalizing therapy for metastatic breast cancer.
AB  - Treatments for metastatic breast cancer are increasingly tailored towards
      individual tumor biology. For tumors that overexpress HER2, progressing on
      trastuzumab and lapatinib, a range of active agents including pertuzumab,
      neratinib and trastuzumab-MCC-DM1, have demonstrated activity when combined with
      trastuzumab. In HER2-normal metastatic breast cancer, recent studies suggest that
      the addition of bevacizumab to first-line chemotherapy improves progression-free
      survival irrespective of choice of cytotoxic agent. Another interesting area of
      investigation is the inhibition of poly-ADP-ribose polymerase, an enzyme
      important for DNA repair. This strategy may be particularly effective in patients
      with inherited defects in DNA repair or by the co-administration of DNA damaging
      cytotoxic chemotherapy. This article covers key new areas of systemic therapy for
      MBC from the American Society of Clinical Oncology 2009 annual meeting.

PMID- 19761427
TI  - Management of conjunctival melanoma.
AB  - Invasive conjunctival melanoma can arise de novo, from nevus or from melanoma in
      situ. The literature reports that after treatment of invasive conjunctival
      melanoma more than 50% of patients develop local tumor recurrence, with 20%
      eventually requiring orbital exenteration and 20-30% developing fatal metastasis.
      Our results have improved since we replaced adjuvant cryotherapy with
      radiotherapy and topical chemotherapy. There is scope for multicenter clinical
      trials and translational research, but these require consistent staging and
      grading of disease. We propose that the term 'primary acquired melanosis' should
      only be used clinically, when the histology is not known. We have devised a
      clinical system for mapping conjunctival melanocytic lesions and a system for
      scoring the histological grade of atypia of conjunctival melanocytic intra
      epithelial neoplasia/melanoma in situ. We anticipate that these measures will
      improve outcomes after treatment of conjunctival melanoma in situ and invasive
      melanoma.

PMID- 19761429
TI  - Molecular profiling of laryngeal cancer.
AB  - Head and neck squamous cell carcinoma, including laryngeal cancer, is considered
      to progress from dysplasia to invasive cancer through well-defined clinical and
      histological stages. Numerous genetic alterations have been described in
      laryngeal squamous cell carcinoma, but the molecular mechanisms contributing to
      initiation and progression of laryngeal cancer are still poorly understood.
      Genomic, transcriptomic and protein alterations in laryngeal cancer progression
      are key areas for the current research aimed at finding instruments for
      classification, prognostication and patient-tailored treatment. We present a
      review of the current literature and discuss the use of array-based technologies
      in revealing the molecular portrait of laryngeal cancer.

PMID- 19761428
TI  - Is there a role for complementary therapy in the management of leukemia?
AB  - Patients with leukemia often seek additional treatments not prescribed by their
      oncologist in an effort to improve their cancer treatment outcome or to manage
      symptoms. Complementary therapies are used in conjunction with traditional cancer
      treatments to decrease symptoms and side effects associated with cancer or cancer
      treatment, and to improve patients' overall quality of life. Complementary
      therapies are distinct from so-called 'alternative' therapies, which are
      unproven, ineffective and may postpone or interfere with mainstream cancer
      treatment. Complementary therapies are pleasant, inexpensive, nonpharmacologic
      and effective. For patients with leukemia, the complementary therapies that are
      always appropriate include mind-body interventions, such as self-hypnosis,
      meditation, guided imagery and breath awareness. Massage and reflexology (foot
      massage) decrease symptoms with effects lasting at least 2 days following
      treatment. Acupuncture is very beneficial for symptom management without adverse
      consequences. Physical fitness with regular exercise and healthy dietary habits
      can significantly decrease side effects of cancer treatments and may prolong
      survival. Botanical extracts and vitamin supplements may interfere with active
      cancer treatments, and should be discussed with the oncologist or pharmacist
      before use.

PMID- 19761430
TI  - Clinicopathologic and molecular disease prognostication for papillary thyroid
      cancer.
AB  - Despite its increasing incidence over the last 30 years, the mortality rate of
      papillary thyroid cancer (PTC) has decreased significantly. Nevertheless, a
      minority of patients still present with an aggressive form of PTC that can lead
      to death, even after a prolonged period of survival. Many classifications exist
      that allow one to stratify the clinical risk of recurrence and death in patients
      with PTC; however, the parameters upon which they are established are
      pathological and molecular and, therefore, are revealed only after surgery. The
      preoperative identification of these aggressive variants of PTC would allow one
      to schedule a more aggressive operation (e.g., total thyroidectomy together with
      central and/or mono- or bi-lateral node dissections) in patients with high-risk
      PTC. This article reviews the parameters used most commonly to differentiate low
      risk PTCs from their more aggressive variants and describes some of the newest
      molecular therapies for this latter group of tumors.

PMID- 19761431
TI  - Managing malignancies of the external auditory canal.
AB  - The ear canal, middle ear and temporal bone are rare sites of primary cancer.
      However, given its central location within the skull base, the tumors from these
      sites often extend to involve the parotid, overlying skin and even the dura or
      carotid artery. Squamous cell carcinoma is the most common histology for both
      primary and secondary tumors. The rarity of temporal bone cancers and the
      complexity of the region's anatomy make treating temporal bone malignancies
      difficult. While early-stage cancers can be effectively treated by complete
      resection, multimodal therapy is imperative for most of these tumors. A
      contemporary review of the literature is presented with present-day controversies
      outlined.

PMID- 19761432
TI  - Role of nucleophosmin in acute myeloid leukemia.
AB  - Nucleophosmin (NPM) is a nucleolar phosphoprotein implicated in the regulation of
      multiple cellular functions, which possesses both oncogenic and tumor-suppressor
      properties. Mutations of the NPM1 gene leading to the expression of a cytoplasmic
      mutant protein, NPMc+, are the most frequent genetic abnormalities found in acute
      myeloid leukemias. Acute myeloid leukemias with mutated NPM1 have distinct
      characteristics, including a significant association with a normal karyotype,
      involvement of different hematopoietic lineages, a specific gene-expression
      profile and clinically, a better response to induction therapy and a favorable
      prognosis. NPMc+ maintains the capacity of wild-type NPM to interact with a
      variety of cellular proteins, and impairs their activity by delocalizing them to
      the cytoplasm. In this review we summarize recent discoveries concerning NPM
      function, and discuss their possible impact on the pathogenesis of acute myeloid
      leukemias with mutated NPM1.

PMID- 19761433
TI  - Recent breakthroughs in the understanding and management of chronic eosinophilic
      leukemia.
AB  - The term hypereosinophilic syndrome (HES) was initially introduced to describe a
      group of diseases all characterized by persistent unexplained hypereosinophilia.
      Additional names have subsequently been introduced to describe specific variants
      of HES, such as the myeloid variant and the lymphoid variant, or to indicate
      idiopathic HES, for which the cause of the eosinophilia is completely unknown.
      Molecular analysis led to the identification of the clonal origin of several
      subgroups of HES, clearly establishing these diseases as true leukemias. These
      cases of hypereosinophilia are now referred to as 'myeloid neoplasms associated
      with eosinophilia and abnormalities of PDGF receptor A and B (PDGFRA and PDGFRB),
      or FGF receptor 1 (FGFR1)'. In cases for which clonality is clear, but no PDGFRA,
      PDGFRB or FGFR1 rearrangement could be demonstrated, the term 'chronic
      eosinophilic leukemia, not otherwise specified' is preferred. Most importantly,
      patients with rearrangements of PDGFRA or PDGFRB can be efficiently treated with
      the kinase inhibitor imatinib. Additional potent kinase inhibitors have been
      identified, also including inhibitors that target FGFR1 and imatinib-resistant
      variants of PDGFRalpha. For treatment of unexplained hypereosinophilia and
      'chronic eosinophilic leukemia, not otherwise specified; different therapeutic
      strategies are currently under investigation and promising results have been
      obtained using humanized anti-IL-5 antibodies. Further molecular understanding of
      the cause of these 'idiopathic' diseases may lead to the development of novel
      targeted therapies.

PMID- 19761434
TI  - Emerging therapies for B-cell non-Hodgkin lymphoma.
AB  - In recent years considerable progress has been made in the treatment of patients
      with B-cell non-Hodgkin lymphoma (NHL). Although responses can be achieved with
      combination chemotherapy regimens, a substantial proportion of patients are still
      not cured. In recent years, the knowledge of the cellular and molecular biology
      of distinct types of B-cell NHL have led to the development of a new class of
      drugs that specifically targets unique disease-specific pathways. This review
      will focus on novel therapies that are being developed for the treatment of B
      cell NHL including those targeting the B-cell receptor signaling pathway, the
      proteasome, epigenetic lesions, novel anti-apoptotic drugs, new monoclonal
      antibodies and immunomodulatory drugs.

PMID- 19761435
TI  - Tumor immunosuppressive environment: effects on tumor-specific and nontumor
      antigen immune responses.
AB  - The interactions between cancer cells and host immune cells in tumoral
      microenvironments create an immunosuppressive network that promotes tumor growth,
      protects the tumor from immune attack and attenuates the efficacy of
      immunotherapeutic approaches. The development of immune tolerance becomes
      predominant in the immune system of patients with advanced-stage tumors. Several
      mechanisms have been described by which tumors can suppress the immune system,
      including secretion of cytokines, alterations in antigen-presenting cell subsets,
      costimulatory and coinhibitory molecule alterations and altered ratios of Tregs
      to effector T cells. It is well demonstrated that these mechanisms of
      immunosuppression can impair tumor specific immune responses. However, it is not
      well established whether this immunosuppressive environment can affect immune
      responses to nontumor antigens, specifically in regard to priming and the
      development of memory. The few existing studies indicate that responses to
      nontumor antigens seem unaffected, although there is still a deep lack of
      understanding of this phenomenon. This is an important issue regarding patient
      endurance and quality of life. Here, we review the existing evidence on
      immunosuppression promoted by tumors, with particular attention to its impact on
      specific immune responses. Understanding these interactions can help us subvert
      tumor-induced tolerance and optimize anti-tumor therapy.

PMID- 19761439
TI  - Genotoxicity studies on HM10760A, recombinant human erythropoietin conjugated to
      globin fragment.
AB  - HM10760A is a recombinant human erythropoietin chemically conjugated to the N
      terminus of human immunoglobulin Fc fragment through a polyethylene glycol
      linker. HM10760A was shown to have a relatively long half-life, compared with
      unconjugated recombinant erythropoietin. In this study, the genotoxicity of
      HM10760A was investigated by using a test battery of three different methods. In
      the Ames assay, five strains (TA100, TA1535, TA98, TA1537, and Escherichia coli
      WP2 uvrA) were tested at six concentrations of 3.13, 6.25, 12.5, 25, 50, and
      100microg/plate. HM10760A did not increase the number of revertant colonies in
      any tester strains with and without metabolic activation by rat-liver S9 mix.
      Subsequently, in vitro chromosomal aberration test, using Chinese hamster lung
      cells, were conducted at the concentrations of 25, 50, and 100microg/mL. HM10760A
      did not induce chromosomal aberrations either in the short-period (6 hours) test
      with or without rat-liver S9 mix or in the continuous-treatment (24 hours) test.
      In the in vivo bone marrow micronucleus assay using the male ICR (imprinting
      control region) mouse, HM10760A was subcutaneously administered twice at 24-hour
      intervals at doses of 0, 150, 300, and 600microg/kg. HM10760A produced a slight,
      but statistically significant, increase in the frequency of micronucleated
      polychromatic erythrocytes at 600microg/kg. However, no biological significance
      was assumed, because this value was within the historical control range. From
      these findings obtained from the genotoxicity assays performed in this study, it
      appears unlikely that HM10760A acts as a genotoxic agent in vitro and in vivo.

PMID- 19761441
TI  - Convergent evolution of coenzyme M biosynthesis in the Methanosarcinales:
      cysteate synthase evolved from an ancestral threonine synthase.
AB  - The euryarchaeon Methanosarcina acetivorans has no homologues of the first three
      enzymes that produce the essential methanogenic coenzyme M (2
      mercaptoethanesulfonate) in Methanocaldococcus jannaschii. A single M.
      acetivorans gene was heterologously expressed to produce a functional
      sulfopyruvate decarboxylase protein, the fourth canonical enzyme in this
      biosynthetic pathway. An adjacent gene, at locus MA3297, encodes one of the
      organism's two threonine synthase homologues. When both paralogues from this
      organism were expressed in an Escherichia coli threonine synthase mutant, the
      MA1610 gene complemented the thrC mutation, whereas the MA3297 gene did not. Both
      PLP (pyridoxal 5'-phosphate)-dependent proteins were heterologously expressed and
      purified, but only the MA1610 protein catalysed the canonical threonine synthase
      reaction. The MA3297 protein specifically catalysed a new beta-replacement
      reaction that converted L-phosphoserine and sulfite into L-cysteate and inorganic
      phosphate. This oxygen-independent mode of sulfonate biosynthesis exploits the
      facile nucleophilic addition of sulfite to an alpha,beta-unsaturated intermediate
      (PLP-bound dehydroalanine). An amino acid sequence comparison indicates that
      cysteate synthase evolved from an ancestral threonine synthase through gene
      duplication, and the remodelling of active site loop regions by amino acid
      insertion and substitutions. The cysteate product can be converted into
      sulfopyruvate by an aspartate aminotransferase enzyme, establishing a new
      convergent pathway for coenzyme M biosynthesis that appears to function in
      members of the orders Methanosarcinales and Methanomicrobiales. These differences
      in coenzyme M biosynthesis afford the opportunity to develop methanogen
      inhibitors that discriminate between the classes of methanogenic archaea.

PMID- 19761442
TI  - Switchgrass (Panicum virgatum) possesses a divergent family of cinnamoyl CoA
      reductases with distinct biochemical properties.
AB  - The down-regulation of enzymes of the monolignol pathway results in reduced
      recalcitrance of biomass for lignocellulosic ethanol production. Cinnamoyl CoA
      reductase (CCR) catalyzes the first step of the phenylpropanoid pathway
      specifically dedicated to monolignol biosynthesis. However, plants contain
      multiple CCR-like genes, complicating the selection of lignin-specific targets.
      This study was undertaken to understand the complexity of the CCR gene family in
      tetraploid switchgrass (Panicum virgatum) and to determine the biochemical
      properties of the encoded proteins. Four switchgrass cDNAs (most with multiple
      variants) encoding putative CCRs were identified by phylogenetic analysis,
      heterologously expressed in Escherichia coli, and the corresponding enzymes were
      characterized biochemically. Two cDNAs, PvCCR1 and PvCCR2, encoded enzymes with
      CCR activity. They are phylogenetically distinct, differentially expressed, and
      the corresponding enzymes exhibited different biochemical properties with regard
      to substrate preference. PvCCR1 has higher specific activity and prefers feruloyl
      CoA as substrate, whereas PvCCR2 prefers caffeoyl and 4-coumaroyl CoAs. Allelic
      variants of each cDNA were detected, but the two most diverse variants of PvCCR1
      encoded enzymes with similar catalytic activity. Based on its properties and
      expression pattern, PvCCR1 is probably associated with lignin biosynthesis during
      plant development (and is therefore a target for the engineering of improved
      biomass), whereas PvCCR2 may function in defense.

PMID- 19761443
TI  - Actin and myosin regulate cytoplasm stiffness in plant cells: a study using
      optical tweezers.
AB  - Here, we produced cytoplasmic protrusions with optical tweezers in mature BY-2
      suspension cultured cells to study the parameters involved in the movement of
      actin filaments during changes in cytoplasmic organization and to determine
      whether stiffness is an actin-related property of plant cytoplasm. Optical
      tweezers were used to create cytoplasmic protrusions resembling cytoplasmic
      strands. Simultaneously, the behavior of the actin cytoskeleton was imaged. After
      actin filament depolymerization, less force was needed to create cytoplasmic
      protrusions. During treatment with the myosin ATPase inhibitor 2,3-butanedione
      monoxime, more trapping force was needed to create and maintain cytoplasmic
      protrusions. Thus, the presence of actin filaments and, even more so, the
      deactivation of a 2,3-butanedione monoxime-sensitive factor, probably myosin,
      stiffens the cytoplasm. During 2,3-butanedione monoxime treatment, none of the
      tweezer-formed protrusions contained filamentous actin, showing that a 2,3
      butanedione monoxime-sensitive factor, probably myosin, is responsible for the
      movement of actin filaments, and implying that myosin serves as a static cross
      linker of actin filaments when its motor function is inhibited. The presence of
      actin filaments does not delay the collapse of cytoplasmic protrusions after
      tweezer release. Myosin-based reorganization of the existing actin cytoskeleton
      could be the basis for new cytoplasmic strand formation, and thus the production
      of an organized cytoarchitecture.

PMID- 19761444
TI  - Tree endurance on the Tibetan Plateau marks the world's highest known tree line
      of the Last Glacial Maximum.
AB  - Because of heterogeneous topographies, high-mountain areas could harbor a
      significant pool of cryptic forest refugia (glacial microrefugia unrecognized by
      palaeodata), which, as a result of poor accessibility, have been largely
      overlooked. The juniper forests of the southern Tibetan Plateau, with one of the
      highest tree lines worldwide, are ideal for assessing the potential of high
      mountain areas to harbor glacial refugia. Genetic evidence for Last Glacial
      Maximum (LGM) endurance of these microrefugia is presented using paternally
      inherited chloroplast markers. Five-hundred and ninety individuals from 102
      populations of the Juniperus tibetica complex were sequenced at three polymorphic
      chloroplast regions. Significant interpopulation differentiation and
      phylogeographic structure were detected (G(ST) = 0.49, N(ST) = 0.72, N(ST) >
      G(ST), P < 0.01), indicating limited among-population gene flow. Of 62 haplotypes
      recovered, 40 were restricted to single populations. These private haplotypes and
      overall degrees of diversity were evenly spread among plateau and edge
      populations, strongly supporting the existence of LGM microrefugia throughout the
      present distribution range, partly well above 3500 m. These results mark the
      highest LGM tree lines known, illustrating the potential significance of high
      mountain areas for glacial refugia. Furthermore, as the close vicinity of
      orographic rear-edge and leading-edge populations potentially allows gene flow,
      surviving populations could preserve the complete spectrum of rear-edge and
      leading-edge adaptations.

PMID- 19761445
TI  - The NADPH-oxidase AtrbohB plays a role in Arabidopsis seed after-ripening.
AB  - *Seeds can enter a state of dormancy, in which they do not germinate under
      optimal environmental conditions. Dormancy can be broken during seed after
      ripening in the low-hydrated state. *By screening enhancer trap lines of
      Arabidopsis, we identified a role for the NADPH-oxidase AtrbohB in after
      ripening. Semiquantitative PCR was used to investigate AtrbohB transcripts in
      seeds. These methods were complemented with a pharmacological approach using the
      inhibitor diphenylene iodonium chloride (DPI) and biomechanical measurements in
      the Brassicaceae seed model system cress (Lepidium sativum) as well as protein
      carbonylation assays. *atrbohB mutants fail to after-ripen and show reduced
      protein oxidation. AtrbohB pre-mRNA is alternatively spliced in seeds in a
      hormonally and developmentally regulated manner. AtrbohB is a major producer of
      superoxide in germinating Arabidopsis seeds, and inhibition of superoxide
      production by diphenylene iodonium (DPI) leads to a delay in Arabidopsis and
      cress seed germination and cress endosperm weakening. *Reactive oxygen species
      produced by AtrbohB during after-ripening could act via abscisic acid (ABA)
      signalling or post-translational protein modifications. Alternative splicing
      could be a general mechanism in after-ripening: by altered processing of stored
      pre-mRNAs seeds could react quickly to environmental changes.

PMID- 19761446
TI  - Zinc distribution and speciation in Arabidopsis halleri x Arabidopsis lyrata
      progenies presenting various zinc accumulation capacities.
AB  - The purpose of this study was to investigate the relationship between the
      chemical form and localization of zinc (Zn) in plant leaves and their Zn
      accumulation capacity. An interspecific cross between Arabidopsis halleri sp.
      halleri and Arabidopsis lyrata sp. petrea segregating for Zn accumulation was
      used. Zinc (Zn) speciation and Zn distribution in the leaves of the parent plants
      and of selected F(1) and F(2) progenies were investigated by spectroscopic and
      microscopic techniques and chemical analyses. A correlation was observed between
      the proportion of Zn being in octahedral coordination complexed to organic acids
      and free in solution (Zn-OAs + Zn(aq)) and Zn content in the leaves. This pool
      varied between 40% and 80% of total leaf Zn depending on the plant studied.
      Elemental mapping of the leaves revealed different Zn partitioning between the
      veins and the leaf tissue. The vein : tissue fluorescence ratio was negatively
      correlated with Zn accumulation. The higher proportion of Zn-OAs + Zn(aq) and the
      depletion of the veins in the stronger accumulators are attributed to a higher
      xylem unloading and vacuolar sequestration in the leaf cells. Elemental
      distributions in the trichomes were also investigated, and results support the
      role of carboxyl and/or hydroxyl groups as major Zn ligands in these cells.

PMID- 19761447
TI  - Introduction--epileptogenic cortical dysplasia: emerging trends in diagnosis,
      treatment, and pathogenesis.

PMID- 19761448
TI  - Focal brain malformations: seizures, signaling, sequencing.
AB  - Focal malformations of cortical development are highly associated with
      intractable epilepsy in children and adults. Most patients with focal cortical
      malformations and epilepsy will require epilepsy surgery. Recent studies have
      provided new insights into the developmental pathogenesis of cortical
      malformations specifically relating to alterations in cell signaling though the
      mammalian target of rapamycin (mTOR) pathway. Focal cortical dysplasias,
      hemimegalencephaly, and tubers in tuberous sclerosis complex all exhibit evidence
      for hyperactive mTOR signaling, suggesting that these disorders form a spectrum
      of malformations or "TORopathies" characterized by disorganized cortical
      lamination, cytomegaly, and intractable seizures. Alterations in mTOR activity in
      focal brain malformations provide a potential pathogenic pathway to investigate
      for gene mutations and to exploit for animal models. Most importantly, however,
      if select focal cortical malformations result from enhanced mTOR signaling, new
      therapeutic antiepileptic compounds, such as rapamycin, can be designed and
      tested that specifically target mTOR signaling.

PMID- 19761449
TI  - New directions in clinical imaging of cortical dysplasias.
AB  - Neuroimaging is essential in the work-up of patients with intractable epilepsy.
      In pediatric patients with medically refractory epilepsy, cortical dysplasias
      account for a large percentage of the epileptogenic substrate. Unfortunately,
      these are also the most subtle lesions to identify. For this reason, there has
      been ongoing interest in utilizing new advanced magnetic resonance imaging (MRI)
      techniques to improve the ability to identify, diagnose, characterize, and
      delineate cortical dysplasias. Technologic gains such as multichannel coils (32
      phased array and beyond) and higher field strengths (3T, 7T, and greater) coupled
      with newer imaging sequences such as arterial spin labeling (ASL), susceptibility
      weighted imaging (SWI) and diffusion tensor/spectrum imaging (DTI/DSI) are likely
      to increase yield. Improved MRI techniques coupled with a multimodality approach
      including magnetoencephalography (MEG), positron emission tomography (PET), and
      other techniques will increase sensitivity and specificity for identifying
      cortical dysplasias.

PMID- 19761450
TI  - Clinical, functional, and neurophysiologic assessment of dysplastic cortical
      networks: Implications for cortical functioning and surgical management.
AB  - Cortical malformations are highly epileptogenic lesions associated with complex,
      unanticipated, and often aberrant electrophysiologic and functional
      relationships. These relationships are inextricably linked to widespread cortical
      networks subserving eloquent functions, particularly language and motor ability.
      Cytomegalic neurons but not balloon cells in Palmini type 2 dysplastic cortex are
      intrinsically hyperexcitable and contribute to local epileptogenesis and
      functional responsiveness. However, there is much evidence that focal cortical
      dysplasia is rarely a localized or even regional process, and is a functionally,
      electrophysiologically, and ultimately clinically integrated neural network
      disorder. Not surprisingly, malformed cortex is implicated in cognitive
      dysfunction, particularly disturbances of linguistic processing. An understanding
      of these relationships is critical for successful epilepsy surgery. Gains in
      surgical prognosis rely on multiple diagnostic modalities to delineate complex
      anatomic, electrophysiologic, and functional relationships in magnetic resonance
      imaging (MRI)-negative patients with rates of seizure-freedom roughly comparable
      to lesional patients.

PMID- 19761451
TI  - From human tissue to animal models: Insights into the pathogenesis of cortical
      dysplasia.
AB  - Cortical dysplasia, a malformation of the cerebral cortex of developmental
      origin, accounts for most cases of drug-resistant childhood epilepsy. Despite its
      prevalence, the genetic and molecular bases for the disease are not known for
      most cases. With the exception of tuberous sclerosis complex, a type of cortical
      malformation with known genetic etiology, no mutated genes have been identified
      that can lead to the neuroanatomic abnormalities observed in the patients.
      Furthermore, there are currently no animal models that completely recapitulate
      the features of the disease, hindering progress in developing new treatments for
      this devastating condition. In this article, I review some of the approaches that
      researchers in the field are undertaking to utilize the biopsy tissue obtained
      from patients with cortical dysplasia who are undergoing epilepsy surgery. These
      multifaceted approaches are providing a plethora of new information that is then
      utilized to generate and evaluate animal models and to further our understanding
      of the disease. These studies will enable the development of novel antiepileptic
      treatments for patients with cortical dysplasia and similar disorders.

PMID- 19761452
TI  - Animal models of focal cortical dysplasia and tuberous sclerosis complex: recent
      progress toward clinical applications.
AB  - Focal cortical dysplasia (FCD) and related malformations of cortical development
      (MCDs) represent an increasingly recognized cause of medically intractable
      epilepsy. However, the underlying mechanisms of epileptogenesis are poorly
      understood, and treatments for epilepsy due to various cortical malformations are
      often limited or ineffective. Animal models offer a number of advantages for
      investigating cellular and molecular mechanisms of epileptogenesis and developing
      novel, rational therapies for MCD-related epilepsy. This review highlights
      specific examples of how animal models have been useful in addressing several
      clinically relevant issues about epilepsy due to FCDs and related cortical
      malformations, including the pathologic and clinical features, etiologic factors,
      localization of the epileptogenic zone, neuronal and astrocytic contributions to
      epileptogenesis, and the development of antiepileptogenic therapies.

PMID- 19761453
TI  - Challenges in the surgical treatment of epilepsy patients with cortical
      dysplasia.
AB  - Cortical dysplasia (CD) is the most common malformation of cortical development
      in epilepsy surgery patients. Patients with mild Palmini type I CD represent
      about 50% of the surgical cases, and these lesions tend to occur most often in
      the temporal lobe, often associated with hippocampal sclerosis. By comparison,
      patients with severe type II CD present at younger ages, often with multilobar
      extratemporal lesions, and more aggressive seizures. The presurgical evaluation
      in CD patients can be challenging, as no single test is 100% accurate. Based on
      retrospective cohort studies, the accuracy of investigations are: interictal
      scalp electroencephalography (EEG), 50%; ictal scalp EEG, 65%; magnetic resonance
      imaging (MRI), 66%; fluorodeoxyglucose-positron emission tomography (FDG-PET),
      81%; and ictal single photon emission computed tomography (SPECT), 57%.
      Intracranial electrodes are used in about 50% of patients with CD. Contemporary
      series report that 62% of patients with CD are seizure free after resective
      neurosurgery, with higher rates for complete (77%) compared with incomplete (20%)
      removal of the lesion. Morbidity (<3%) and mortality (0.2%) are low for patients
      with CD undergoing epilepsy neurosurgery. Future challenges include the
      noninvasive identification of patients with CD with 100% accuracy, evaluation of
      long-term outcomes in surgical patients, and devising new treatments based on a
      better understanding of the neurobiology leading to seizures in CD tissue.

PMID- 19761455
TI  - Testing of a measurement model for baccalaureate nursing students' self
      evaluation of core competencies.
AB  - TITLE: Testing of a measurement model for baccalaureate nursing students' self
      evaluation of core competencies. AIM: This paper is a report of a study to test
      the psychometric properties of the Self-Evaluated Core Competencies Scale for
      baccalaureate nursing students. BACKGROUND: Baccalaureate nursing students
      receive basic nursing education and continue to build competency in practice
      settings after graduation. Nursing students today face great challenges. Society
      demands analytic, critical, reflective and transformative attitudes from
      graduates. It also demands that institutions of higher education take the
      responsibility to encourage students, through academic work, to acquire knowledge
      and skills that meet the needs of the modern workplace, which favours highly
      skilled and qualified workers. METHODS: A survey of 802 senior nursing students
      in their last semester at college or university was conducted in Taiwan in 2007
      using the Self-Evaluated Core Competencies Scale. Half of the participants were
      randomly assigned either to principal components analysis with varimax rotation
      or confirmatory factor analysis. RESULTS: Principal components analysis revealed
      two components of core competencies that were named as humanity/responsibility
      and cognitive/performance. The initial model of confirmatory factor analysis was
      then converged to an acceptable solution but did not show a good fit; however,
      the final model of confirmatory factor analysis was converged to an acceptable
      solution with acceptable fit. The final model has two components, namely
      humanity/responsibility and cognitive/performance. Both components have four
      indicators. In addition, six indicators have their correlated measurement errors.
      CONCLUSION: Self-Evaluated Core Competencies Scale could be used to assess the
      core competencies of undergraduate nursing students. In addition, it should be
      used as a teaching guide to increase students' competencies to ensure quality
      patient care in hospitals.

PMID- 19761456
TI  - Parenting self-efficacy after childbirth.
AB  - TITLE: Parenting self-efficacy after childbirth. AIM: This paper is a report of
      study of parent, infant and environmental correlates of mothers' and fathers'
      perceptions of their parenting self-efficacy. BACKGROUND: Many parents are not
      confident in their ability to be good parents. Parenting self-efficacy is
      important for parents' sense of well-being, is a possible predictor of parenting
      practices and might be an indicator of risk. However, very little evidence exists
      on factors that influence fathers' perceptions of parenting, or comparisons
      between the parents. METHODS: The data were collected by questionnaire in 2006
      2007 in two hospitals with a convenience sample of Finnish-speaking parents (N =
      1300 families) during the first postpartum week. Multiple-birth and early
      discharge parents were excluded. The response rate for mothers was 66% (n = 863)
      and for fathers 40% (n = 525). Comparisons were made by percentages and means.
      Statistical significance was determined by Generalized Estimating Equations
      models and one-way anova. Pearson's and Spearman's correlation coefficients were
      used to determine correlations, and multiple regression analysis to clarify the
      effect size. RESULTS: Mothers scored higher than fathers on parenting self
      efficacy. Parity, self-concept, depressive symptoms and state of mind on
      discharge contributed to parenting self-efficacy. Experiences of childbirth and
      life change correlated with mothers', but not with fathers', parenting self
      efficacy. Perceptions of infant, family functioning, health and advice from
      personnel were major contributory factors. CONCLUSION: Assessments of parenting
      self-efficacy are recommended to identify at-risk groups and at-risk parents.
      More research is recommended to look into the effect of rooming-in, feeding
      practices, fathers' presence and social support from personnel and parenting self
      efficacy and to evaluate risk scales for at-risk parents. Parent attributes had a
      greater effect on mothers' parenting self-efficacy, while environmental
      attributes had a greater effect on fathers' parenting self-efficacy. At-risk
      parents can be supported by conducting face-to-face discussions about significant
      topics.

PMID- 19761457
TI  - Correlates of recent and regular mammography screening among Asian-American
      women.
AB  - TITLE: Correlates of recent and regular mammography screening among Asian
      American women. AIM: This paper is a report of a study of the health beliefs,
      knowledge and selected demographic variables that influence mammography
      utilization among Asian-American women. BACKGROUND: Breast cancer is the most
      frequently occurring cancer in Asian-American women and its incidence is
      increasing at a greater rate than for other racial and ethnic groups in the
      United States of America (USA). Compared to White women, breast cancer also is
      more likely to be diagnosed at a later stage with larger tumours in Asian
      Americans. METHOD: A self-administered questionnaire was used with Asian-American
      women residing in the USA. Data were collected in 2005 and 315 women participated
      in the study. RESULTS: Fifty-five per cent of participants reported having their
      last mammogram within the past 13 months, and 33% reported having annual
      mammograms in each of the past 5 years. Based on multivariate logistic regression
      analyses, clinical breast examination, barriers and knowledge of recommendations
      of the frequency of mammography screening were associated with both recent and
      regular mammography practice after controlling for all other demographic,
      psychosocial and behavioural variables in the model. CONCLUSION: Intervention
      strategies tailored to knowledge, language and cultural factors associated with
      mammography use should target at-risk subgroups, particularly those who are
      recent immigrants and those with limited English language ability. Culturally
      appropriate strategies should be developed to promote lifelong mammography
      screening for this rapidly growing and diverse population.

PMID- 19761458
TI  - Empowering surgical nurses improves compliance rates for antibiotic prophylaxis
      after caesarean birth.
AB  - TITLE: Empowering surgical nurses improves compliance rates for antibiotic
      prophylaxis after caesarean birth. AIM: This paper is a report of a study of the
      effect of empowering surgical nurses to ensure that patients receive antibiotic
      prophylaxis after caesarean birth. BACKGROUND: Despite the consensus that single
      dose antibiotic prophylaxis is beneficial for women have either elective or non
      elective caesarean delivery, hospitals need methods to increase compliance rates.
      METHOD: In a study in Israel in 2007 surgical nurses were empowered to ensure
      that a single dose of cefazolin was given to the mother after cord clamping. A
      computerized system was used to identify women having caesarean births, cultures
      sent and culture results. Compliance was determined by chart review. Rates of
      compliance, suspected wound infections, and confirmed wound infections in 2007
      were compared to rates in 2006 before the policy change. Relative risks were
      calculated dividing 2007 rates by those in 2006, and 95% confidence intervals
      were calculated using Taylor's series that does not assume a normal distribution.
      Statistical significance was assessed using the chi-square test. FINDINGS: The
      compliance rate was increased from 25% in 2006 to 100% in 2007 (chi-square test,
      P < 0.001). Suspected wound infection rates decreased from 16.8% (186/1104) to
      12.6% (137/1089) after the intervention (relative risk 0.75, 95% confidence
      interval, 0.61-0.92). CONCLUSION: Surgical nurses can ensure universal compliance
      for antibiotic prophylaxis in women after caesarean birth, leading to a reduction
      in wound infections.

PMID- 19761459
TI  - What determines a species' geographical range? Thermal biology and latitudinal
      range size relationships in European diving beetles (Coleoptera: Dytiscidae).
AB  - 1. The geographical range sizes of individual species vary considerably in
      extent, although the factors underlying this variation remain poorly understood,
      and could include a number of ecological and evolutionary processes. A favoured
      explanation for range size variation is that this result from differences in
      fundamental niche breadths, suggesting a key role for physiology in determining
      range size, although to date empirical tests of these ideas remain limited. 2.
      Here we explore relationships between thermal physiology and biogeography, whilst
      controlling for possible differences in dispersal ability and phylogenetic
      relatedness, across 14 ecologically similar congeners which differ in
      geographical range extent; European diving beetles of the genus Deronectes Sharp
      (Coleoptera, Dytiscidae). Absolute upper and lower temperature tolerance and
      acclimatory abilities are determined for populations of each species, following
      acclimation in the laboratory. 3. Absolute thermal tolerance range is the best
      predictor of both species' latitudinal range extent and position, differences in
      dispersal ability (based on wing size) apparently being less important in this
      group. In addition, species' northern and southern range limits are related to
      their tolerance of low and high temperatures respectively. In all cases, absolute
      temperature tolerances, rather than acclimatory abilities are the best predictors
      of range parameters, whilst the use of independent contrasts suggested that
      species' thermal acclimation abilities may also relate to biogeography, although
      increased acclimatory ability does not appear to be associated with increased
      range size. 4. Our study is the first to provide empirical support for a
      relationship between thermal physiology and range size variation in widespread
      and restricted species, conducted using the same experimental design, within a
      phylogenetically and ecologically controlled framework.

PMID- 19761460
TI  - Rapid in vivo screening system for anti-oxidant activity using bacterial redox
      sensor strains.
AB  - AIM: To develop a faster and easier in vivo method to screen compounds for anti
      oxidant activity using a microbial system. METHODS AND RESULTS: Bacterial redox
      sensor-based assay systems were applied. The activities of SoxR and OxyR, the
      bacterial redox sensors, were monitored to probe the intracellular redox status
      through two reporter strains, Escherichia coli soxS(p)-lacZ and oxyS(p)-lacZ
      fusions, which specifically respond to paraquat, a superoxide generator, and
      H(2)O(2), respectively, with practically no cross reactivity. For the test
      screening, 27 natural compounds including phenolics and flavonoids that are
      putatively considered anti-oxidant nutritional supplements were collected and
      assayed for their capability to alleviate oxidative stress in these bacterial
      systems. Among them, rutin, kaempferol and quercetin had significant anti
      H(2)O(2) activity, and betaine, glycyrrhizic acid and baicalin had weak anti
      superoxide activity. While rutin, kaempferol and quercetin significantly reduced
      the H(2)O(2) stress at low concentrations, betaine, glycyrrhizic acid and
      baicalin required higher concentration for their anti-superoxide effects. In
      vitro, only quercetin protected DNA in a metal-catalysed oxidation system,
      suggesting that the other compounds might indirectly exert their anti-oxidant
      activities through other biological functions. Finally, quercetin, rutin and
      kaempferol significantly restored the viability of a superoxide dismutase mutant
      that has limited viability because of defective defence against oxidative stress.
      CONCLUSION: These bacterial systems could provide a more efficient method for
      measuring the activity of compounds affecting cellular oxidative stress and
      viability. SIGNIFICANCE AND IMPACT OF THE STUDY: The demand for anti-oxidant and
      anti-ageing activities is increasing in one of the fastest growing segments of
      the functional food market, but the screening for these activities is currently
      very laborious, expensive and time consuming. This study suggests a basis for a
      high throughput screening method for these activities.

PMID- 19761461
TI  - Evaluation of water treatment plant UV reactor efficiency against Cryptosporidium
      parvum oocyst infectivity in immunocompetent suckling mice.
AB  - AIM: To assess the efficiency of a medium-pressure UV reactor under full-scale
      water treatment plant (WTP) conditions on the infectivity of Cryptosporidium
      parvum oocysts in an Naval Medical Research Institute (NMRI) suckling mice
      infectivity model. METHODS AND RESULTS: Six/seven-day-old mice were administered
      orally 2-10x10(4)Cryptosporidium parvum oocysts. Compared with nonirradiated
      oocysts, 40 mJ cm(-2) UV irradiation of ingested oocysts resulted 7 days later in
      a 3.4-4.0 log10 reduction in the counts of small intestine oocysts, using a
      fluorescent flow cytometry assay. CONCLUSION: Present data extend to industrial
      conditions previous observations of the efficiency of UV irradiation against
      Cryptosporidium parvum oocyst in vivo development. SIGNIFICANCE AND IMPACT OF THE
      STUDY: Present results suggest that in WTP conditions, a medium-pressure UV
      reactor is efficient in reducing the infectivity of Cryptosporidium parvum
      oocysts, one of the most resistant micro-organisms present in environmental
      waters.

PMID- 19761462
TI  - Development and optimization of an 18S rRNA-based oligonucleotide microarray for
      the fungal order Eurotiales.
AB  - AIMS: For identification of members of the fungal order Eurotiales, an 18S rRNA
      gene-based oligonucleotide microarray was developed and optimized. METHODS AND
      RESULTS: Eurotiales-specific probes covering most members of the Eurotiales as
      well as species-specific probes were designed and evaluated with three pure
      cultures (two fungi from the Eurotiales and one fungus from the Hypocreales).
      Nearly complete 18S rRNA genes of each reference culture were amplified and
      fluorescently labelled by random priming. CONCLUSIONS: Positive and negative
      hybridization results confirmed that the Eurotiales probes tested in this study
      could correctly identify members of the Eurotiales. The species-specific probes
      were also capable of species-level detection. SIGNIFICANCE AND IMPACT OF THE
      STUDY: These findings demonstrate the potential applications of a phylogenetic
      oligonucleotide microarray approach to characterizing fungal species and
      populations in environmental and other samples.

PMID- 19761463
TI  - Viral and bacterial contamination in recreational waters: a case study in the
      Lisbon bay area.
AB  - AIMS: To assess the presence of viral pathogens in bathing water samples and to
      evaluate the interdependency of bacterial indicator counts and viral detection.
      METHODS AND RESULTS: Bathing water samples of 16 beaches collected along a
      Portuguese Coastal area were screened for the hepatitis A virus (HAV) and
      norovirus genogroup I (NVGI) using RT-PCR technique. Bacteriological water
      quality was also assessed, according to European regulations. HAV and NVGI were
      detected in 95% and 27% of the water samples, respectively, whereas
      bacteriological quality was good in all but one sample, according to current
      water quality regulations. CONCLUSIONS: All water samples would be considered of
      excellent quality according to the most recent European regulations. No
      relationship between viral detection and regulatory-based bacterial indicators
      was found. SIGNIFICANCE AND IMPACT OF THE STUDY: The current results reinforce
      the importance of increased surveillance for pathogenic viruses in bathing
      waters.

PMID- 19761464
TI  - Expression of pyrrothine N-acyltransferase activities in Saccharothrix
      algeriensis NRRL B-24137: new insights into dithiolopyrrolone antibiotic
      biosynthetic pathway.
AB  - AIMS: The hypothetical dithiolopyrrolone biosynthetic pathway includes a final
      step of pyrrothine nucleus acylation. The presence of an enzymatic activity
      catalysing this reaction was investigated in Saccharothrix algeriensis NRRL B
      24137. To understand the effect exerted by organic acids on the level of
      dithiolopyrrolone production, their influence on enzymatic expression was
      studied. METHODS AND RESULTS: The transfer of acetyl-CoA or benzoyl-CoA on
      pyrrothine was assayed in the cell-free extract of Sa. algeriensis NRRL B-24137.
      This study reports the presence of an enzymatic activity catalysing this reaction
      that was identified as either pyrrothine N-acetyltransferase or N
      benzoyltransferase. The stimulation of benzoyl-pyrrothine (BEP) production by
      addition of benzoic acid at 1.25 mmol l(-1) into the culture medium was
      demonstrated, and results showed that under the same conditions of growth,
      pyrrothine N-benzoyltransferase specific activity was doubled. CONCLUSIONS: This
      study shows that BEP production is enhanced in the presence of benzoic acid
      partly because of an induction of pyrrothine N-benzoyltransferase. SIGNIFICANCE
      AND IMPACT OF THE STUDY: The antitumor and antibiotic properties of
      dithiolopyrrolones are related to their variable acyl groups. New insights into
      regulation of biosynthetic pathway, especially the step of pyrrothine acylation,
      could lead after further studies to yield improvement and to selective production
      of dithiolopyrrolones with new biological activities.

PMID- 19761465
TI  - Perianal Crohn's disease with a clenched fist-like appearance.

PMID- 19761466
TI  - The increase rates of syphilis in Turkey in the beginning of the third
      millennium.

PMID- 19761470
TI  - Sexuality and personal relationships for people with an intellectual disability.
      Part II: staff and family carer perspectives.
AB  - BACKGROUND: Recent ideological shifts in service provision promote appropriate
      sexual expression for people with an intellectual disability (ID), although there
      is little evidence that such advances in ideology are matched by current service
      provision. Part II of the current two-part study assessed the attitudes of staff
      and family carers to the sexuality of people with an ID. METHOD: A questionnaire
      survey which included case scenarios was carried out with family (n = 155) and
      staff carers (n = 153) of people with an ID in the west of Ireland. RESULTS: In
      general, staff carers were more inclined than family carers to openly discuss
      issues of sexuality with service users, and to suggest environmental, rather than
      service-user characteristics, as impediments to such discussions. Attitudinal
      differences emerged with significant differences between staff and family carers
      and between younger and older carers. Staff carers were more likely to support
      service-user engagement in intimate and non-intimate relationships whereas the
      majority of family carers (80%) showed a preference for low levels of intimacy in
      service-user relationships. CONCLUSION: When compared with the attitudes of
      family carers towards the sexuality of people with ID, the attitudes of staff
      carers more closely match those promoted by ideological developments. However,
      differences in attitudes between carer groups may lead to inconsistent approaches
      to the management of sexuality. As a consequence, we conclude that there is
      continued need to provide staff and family carers with opportunities for dialogue
      and an ongoing need for training in the area of sexuality.

PMID- 19761471
TI  - Soft tissue decomposition of submerged, dismembered pig limbs enclosed in plastic
      bags.
AB  - This study examines underwater soft tissue decomposition of dismembered pig limbs
      deposited in polyethylene plastic bags. The research evaluates the level of
      influence that disposal method has on underwater decomposition processes and
      details observations specific to this scenario. To our knowledge, no other study
      has yet investigated decomposing, dismembered, and enclosed remains in water
      environments. The total sample size consisted of 120 dismembered pig limbs,
      divided into a subsample of 30 pig limbs per recovery period (34 and 71 days) for
      each treatment. The two treatments simulated non-enclosed and plastic enclosed
      disposal methods in a water context. The remains were completely submerged in
      Lake Ontario for 34 and 71 days. In both recovery periods, the non-enclosed
      samples lost soft tissue to a significantly greater extent than their plastic
      enclosed counterparts. Disposal of remains in plastic bags therefore results in
      preservation, most likely caused by bacterial inhibition and reduced oxygen
      levels.

PMID- 19761472
TI  - The effects of soil environment on postmortem interval: a macroscopic analysis.
AB  - Burial environment, in particular soil moisture, has a significant impact on the
      type, rate, and extent of bone degradation, which ultimately affects estimations
      of the postmortem interval (PMI). The purpose of this research is to determine
      the effects of soil moisture on the color, weight, condition, and texture of bone
      as it relates to the PMI. Bone changes occurring over two different time
      intervals (2 and 5 months) were examined using 120 sus scrofa leg bones. During
      each time interval bones were buried in two soil environments, one of which was
      drier than the other. The bones in both environments lost weight over time but
      the net weight loss was greater for bones in the higher moisture environment.
      There was no change in color, texture, or overall condition, indicating that 150
      days is not long enough for such alterations to occur, regardless of the moisture
      level of the burial environment.

PMID- 19761473
TI  - Investigation delayed is justice denied: proposals for expediting forensic
      examinations of digital evidence.
AB  - There is an urgent need to reduce the growing backlog of forensic examinations in
      Digital Forensics Laboratories (DFLs). Currently, DFLs routinely create forensic
      duplicates and perform in-depth forensic examinations of all submitted media.
      This approach is rapidly becoming untenable as more cases involve increasing
      quantities of digital evidence. A more efficient and effective three-tiered
      strategy for performing forensic examinations will enable DFLs to produce useful
      results in a timely manner at different phases of an investigation, and will
      reduce unnecessary expenditure of resources on less serious matters. The three
      levels of forensic examination are described along with practical examples and
      suitable tools. Realizing that this is not simply a technical problem, we address
      the need to update training and establish thresholds in DFLs. Threshold
      considerations include the likelihood of missing exculpatory evidence and
      seriousness of the offense. We conclude with the implications of scaling forensic
      examinations to the investigation.

PMID- 19761475
TI  - Immunohistochemical analysis of P(53) and bcl-2 in benign and malignant salivary
      glands tumors.
AB  - BACKGROUND: Salivary glands tumors are relatively uncommon neoplasm with widely
      variable histopathologic and biologic characteristics. Alteration in some proto
      oncogenes and tumor suppressor genes may lead to the development and progression
      of these tumors. AIMS: The purpose of this study was to analyze the
      immunohistochemical expression of P(53) and bcl-2 in some salivary gland tumors
      in relation to tumor size, histologic grade, and extent of invasion. SETTING AND
      DESIGN: The sample consisted of 22 formalin-fixed paraffin embedded blocks of
      benign and malignant salivary glands tumors. MATERIAL AND METHOD: P(53) and bcl-2
      immunoreactivity was semi-quantitatively evaluated in at least 1000 cells
      examined under the microscope at 40x magnification and recorded as percentage of
      P(53) or bcl-2 positive tumor cells over the total number of cells examined in
      the same area. Percentage scores were subsequently categorized using the 5% cut
      off point for positive staining. RESULTS AND CONCLUSION: Pleomorphic adenoma (PA)
      showed negative expression of P(53) and bcl-2 in 70% of cases, whereas all
      malignant salivary glands tumors were positive for P(53) and bcl-2. P(53)
      positive/bcl-2 positive immunostaining reaction was week in small size PA and was
      totally absent in larger lesions. However, all malignant tumors expressed P(53),
      with the highest record in low-grade adenocarcinoma (76%) and the lowest score
      was observed in both low-grade carcinoma in PA and adenocystic carcinoma. bcl-2
      immunostaining was also assessed, the highest recorded score was in high-grade
      adeno cystic carcinoma (90%) and the lowest in both low-grade carcinoma ex-PA and
      low-grade cystic mucoepidermoid carcinoma (3%). P(53)/bcl-2 immunostaining
      reactivity could be helpful in demonstrating salivary glands tumor behavior in
      terms of progression and extent of invasion.

PMID- 19761474
TI  - Circulating high molecular weight adiponectin isoform is heritable and shares a
      common genetic background with insulin resistance in nondiabetic White Caucasians
      from Italy: evidence from a family-based study.
AB  - OBJECTIVE: Reduced circulating adiponectin levels contribute to the aetiology of
      insulin resistance. Adiponectin circulates in three different isoforms: high
      molecular weight (HMW), medium molecular weight (MMW) and low molecular weight
      (LMW) isoforms. The genetics of adiponectin isoforms is mostly unknown. Our aim
      was to investigate whether and to which extent circulating adiponectin isoforms
      are heritable and whether they share common genetic backgrounds with insulin
      resistance-related traits. METHODS: In a family-based sample of 640 nondiabetic
      White Caucasians from Italy, serum adiponectin isoforms concentrations were
      measured by ELISA. Three single nucleotide polymorphisms (SNPs) in the ADIPOQ
      gene previously reported to affect total adiponectin levels (rs17300539,
      rs1501299 and rs677395) were genotyped. The heritability of adiponectin isoform
      levels was assessed by variance component analysis. A linear mixed effects model
      was used to test the association between SNPs and adiponectin isoforms. Bivariate
      analyses were conducted to study genetic correlations between adiponectin
      isoforms levels and other insulin resistance-related traits. RESULTS: All
      isoforms were highly heritable (h(2) = 0.60-0.80, P = 1.0 x 10(-13)-1.0 x 10(
      23)). SNPs rs17300539, rs1501299 and rs6773957 explained a significant proportion
      of HMW variance (2-9%, P = 1.0 x 10(-3)-1.0 x 10(-5)). In a multiple-SNP model,
      only rs17300539 and rs1501299 remained associated with HMW adiponectin (P = 3.0 x
      10(-4) and 2.0 x 10(-2)). Significant genetic correlations (P = 1.0 x 10(-2)-1.0
      x 10(-5)) were observed between HMW adiponectin and fasting insulin, homeostasis
      model assessment of insulin resistance, HDL cholesterol and the metabolic
      syndrome score. Only rs1501299 partly accounted for these genetic correlations.
      CONCLUSION: Circulating levels of adiponectin isoforms are highly heritable. The
      genetic control of HMW adiponectin is shared in part with insulin resistance
      related traits and involves, but is not limited to, the ADIPOQ locus.

PMID- 19761476
TI  - Plasma and pulmonary fluid endothelin in horses with seasonal recurrent airway
      obstruction.
AB  - BACKGROUND: Summer pasture-associated recurrent airway obstruction (SPA-RAO), a
      seasonal airway obstructive disease of horses, is characterized by clinical
      exacerbation after exposure to pasture during warm months of the year. Endothelin
      (ET)-1, potent bronchoconstrictor, mitogen, secretagogue, and proinflammatory
      mediator, has been implicated in the pathogenesis of asthma and equine heaves.
      HYPOTHESIS: Immunoreactive ET-1 concentrations increase during clinical
      exacerbation and return to basal values during periods of disease remission.
      ANIMALS: Twelve horses, 6 affected with SPA-RAO and 6 nonaffected. METHODS:
      Prospective, observational study. Bronchoalveolar lavage fluid (BALF), arterial
      and venous plasma samples, and clinical variables were obtained from affected
      horses during clinical exacerbation and remission. Samples and data of
      nonaffected horses were collected during the summer and winter on dates similar
      to affected horses. Immunoreactive ET-1 was determined using a commercial ELISA.
      RESULTS: The median and range ET-1 concentrations (pg/ml) in arterial (1.3, 0.7
      1.8) and venous (1.3, 1.2-1.7) plasma and in BALF (0.3, 0.2-0.4), and pulmonary
      epithelial lining fluid (PELF) (25.5, 21-50) were greater in affected horses
      during clinical exacerbation compared with remission (P < .01). The
      concentrations of immunoreactive ET-1 were greater in affected horses during
      clinical exacerbation compared with nonaffected horses (P < .05). CONCLUSIONS AND
      CLINICAL IMPORTANCE: During clinical exacerbation of SPA-RAO, ET-1 is increased
      in circulation and pulmonary secretions. Intervention with ET receptor
      antagonists should provide further information on the role of ET-1 in SPA-RAO.

PMID- 19761477
TI  - Canine granulocytic anaplasmosis: a review.
AB  - Anaplasma phagocytophilum is an emerging pathogen of humans, horses, and dogs
      worldwide that is transmitted by Ixodid ticks and maintained in a variety of
      small wild mammal species. Recent studies suggest that multiple strains of A.
      phagocytophilum may be circulating in wild and domestic animal populations, and
      these strains may have differential host tropisms and pathogenicity. The organism
      infects and survives within neutrophils by disabling key neutrophil functions,
      including neutrophil motility, phagocytosis, the oxidative burst mechanism, and
      neutrophil-endothelial cell interactions, as well as interfering with neutrophil
      apoptosis. Coinfections with other tick-borne pathogens may occur, especially
      Borrelia burgdorferi. A. phagocytophilum causes an acute febrile illness in dogs
      with lethargy and inappetence. Less frequent signs include lameness, coughing,
      polydipsia, intermittent vomiting, and hemorrhages. Diagnosis is based on finding
      morulae within granulocytes in the peripheral blood, the combination of acute and
      convalescent serology using immunofluorescent antibody techniques, and detection
      of the DNA of A. phagocytophilum using specific polymerase chain reaction assays.
      Whether persistent infection or reinfection with A. phagocytophilum occurs after
      natural infection requires additional study, with most reports suggesting that
      anaplasmosis is a self-limiting disease in dogs that responds well to a 2-week
      course of doxycycline therapy.

PMID- 19761480
TI  - Pharmageddon.

PMID- 19761478
TI  - Effects of blood contamination on peritoneal D-dimer concentration in horses with
      colic.
AB  - BACKGROUND: Peritoneal D-Dimer concentration can be determined to assess
      peritoneal fibrinolysis activity in horses with gastrointestinal disorders.
      However, blood contamination of peritoneal fluid may occur during collection and
      could alter peritoneal D-Dimer concentration. HYPOTHESIS/OBJECTIVES: Blood
      contamination in peritoneal fluid does not affect interpretation of peritoneal D
      Dimer concentration in horses with colic. ANIMALS: Thirty-four horses with colic
      and 4 healthy horses. METHODS: Peritoneal fluid and blood samples were
      simultaneously collected upon admission. Then, peritoneal fluid was serially
      contaminated with the horse's own blood; final contaminations corresponded to 1,
      5, 10, and 20% of blood in peritoneal fluid. D-Dimer concentration was determined
      in blood, peritoneal fluid, and contaminated peritoneal fluid samples. Data were
      analyzed using a longitudinal linear model and a generalized estimating equations
      analysis to assess the quantitative and qualitative variations of the effect of
      blood contamination on peritoneal D-Dimer concentration. RESULTS: Peritoneal D
      Dimer concentration was only quantitatively affected when peritoneal fluid was
      contaminated at 20% of blood. However, when using increasing cut-off values of
      peritoneal D-Dimer concentration (100, 2,000, 8,000, and 16,000 ng/mL), this
      effect disappeared at the highest cut-off values (8,000 and 16,000 ng/mL). When
      peritoneal fluid contamination was grouped as "minimally contaminated" (< or =1%
      of blood) and "highly contaminated" (> or =5% of blood), no significant
      differences on D-Dimer concentration between both groups at each cut-off value
      were observed. CONCLUSIONS AND CLINICAL IMPORTANCE: Although quantitative results
      of peritoneal D-Dimer concentration could be affected by high levels of blood
      contamination (> or =20%), interpretation of increased peritoneal fibrinolytic
      activity was not significantly affected.

PMID- 19761481
TI  - Variability in incubator humidity practices in the management of preterm infants.
AB  - AIM: To determine current practice and opinion in relation to incubator humidity
      use in the management of preterm infants in neonatal intensive care units
      (NICU's) within the Australian and New Zealand Neonatal Network (ANZNN). METHODS:
      A survey was conducted in 26 NICU's in the ANZNN. A senior clinical nurse in each
      perinatal centre participated in a telephone survey that focused on local
      humidification practices and on the clinicians' views and experiences of humidity
      use. RESULTS: All centres routinely used supplemental humidity in the management
      of preterm infants. The majority of centres (77%) had written protocols to guide
      practice. Eighty-eight per cent commenced humidity at a high level (relative
      humidity > or = 80%). There was wide practice variation in the gestational age
      parameters determining humidification use (all gestational ages up to 37 weeks),
      duration of use (3-77 days), timing of initiation (admission to 72 h after birth)
      and weaning practices. Perceived benefits of humidification included improved
      thermoregulation, skin integrity, and fluid and electrolyte balance and reduced
      transepidermal water loss. Perceived risks included sepsis and hyperthermia.
      CONCLUSIONS: Our study confirmed that incubator humidity is used routinely in the
      management of preterm infants in the ANZNN. Wide variation in humidification
      practices across NICUs reflects the paucity of research evidence. Perceived
      benefits and risks of humidity use were consistent with available literature. To
      optimise the care environment and provide an evidence base for practice further
      research is warranted.

PMID- 19761482
TI  - In search of quality care for adolescents and young adults with chronic
      conditions.

PMID- 19761486
TI  - Sowing (and mapping) the wild oats.
AB  - Both ecological and molecular methods have been applied to the study of locally
      adapted populations. While Clausen et al. (1940) were the pioneers of field
      transplant studies, the work of Robert Allard et al. on the invasive species
      Avena barbata is a classic example of using molecular evidence to infer
      adaptation via correlation of particular alleles with environmental gradients. In
      a new study published in this issue of Molecular Ecology, Latta (2009) combines
      ecological methods (reciprocal environment studies) with quantitative genetic
      techniques (recombinant inbred lines and quantitative trait analysis) to provide
      new evidence for local adaptation within this well known system. The conclusions
      are orthogonal to the original hypothesis, and instead, provide evidence that
      factors other than local adaptation were likely responsible for the historically
      observed patterns. This new evidence suggests that one ecotype is generally more
      fit than the other in both a moist and a dry environment, and accordingly, it
      appears to be increasing in frequency in historically surveyed populations.

PMID- 19761487
TI  - Evolutionary, behavioural and molecular ecology must meet to achieve long-term
      conservation goals.
AB  - Founder populations in reintroduction programmes can experience a genetic
      bottleneck simply because of their small size. The influence of reproductive skew
      brought on by polygynous or polyandrous mating systems in these populations can
      exacerbate already difficult conservation genetic problems, such as inbreeding
      depression and loss of adaptive potential. Without an understanding of
      reproductive skew in a target species, and the effect it can have on genetic
      diversity retained over generations, long-term conservation goals will be
      compromised. In this issue of Molecular Ecology, Miller et al. (2009a) test how
      founder group size and variance in male reproductive success influence the
      maintenance of genetic diversity following reintroduction on a long-term scale.
      They evaluated genetic diversity in two wild populations of the iconic New
      Zealand tuatara (Fig. 1), which differ greatly in population size and genetic
      diversity, and compared this to genetic diversity in multiple founder populations
      sourced from both populations. Population viability analysis on the maintenance
      of genetic diversity over 400 years (10 generations) demonstrated that while the
      loss of heterozygosity was low when compared with both source populations (1
      14%), the greater the male reproductive skew, the greater the predicted losses of
      genetic diversity. Importantly however, the loss of genetic diversity was
      ameliorated after population size exceeded 250 animals, regardless of the level
      of reproductive skew. This study demonstrates that highly informed conservation
      decisions could be made when you build on a solid foundation of demographic,
      natural history and behavioural ecology data. These data, when informed by modern
      population and genetic analysis, mean that fundamental applied conservation
      questions (how many animals should make up a founder population?) can be answered
      accurately and with an eye to the long-term consequences of management decisions.

PMID- 19761488
TI  - Poststernotomy sternal osteomyelitis and mediastinitis by Trichosporon asahii: a
      rare occurrence with a grave prognosis.
AB  - Post-sternotomy infectious complications, including superficial and deep wound
      infections, sternal osteomyelitis and mediastinitis, are rarely caused by fungi.
      Trichosporon asahii is the main Trichosporon species that causes systemic
      infection in humans. Most cases involved neutropenic patients with hematologic
      malignancies. We report a unique case of a non-cancer, non-neutropenic but
      severely ill patient who developed an ultimately lethal T. asahii infection after
      sternotomy. We speculate that our patient had been colonized with the fungus and
      his surgical site infection may have been related to his emergency
      revascularization surgery. Therapy with liposomal amphotericin failed to
      sterilize the bloodstream despite in vitro susceptibility results. The addition
      of voriconazole helped sterilizing the bloodstream without changing the outcome.
      Physicians must be aware of the continuously expanding spectrum of infections
      with this emerging difficult-to-treat fungal pathogen.

PMID- 19761489
TI  - In vitro efficacy of amphotericin B, 5-fluorocytosine, fluconazole, voriconazole
      and posaconazole against Candida dubliniensis isolates using time-kill
      methodology.
AB  - Candida dubliniensis is a recently described yeast that causes infections in
      mucosal surfaces as well as sterile body sites. Candida dubliniensis develops
      resistance to fluconazole (FLC) more rapidly than the closely related species C.
      albicans. The killing activity of amphotericin B (AMB), 5-fluorocytosine (5FC),
      FLC, voriconazole (VRC) and posaconazole (POS) was determined against six C.
      dubliniensis clinical isolates, identified using molecular biological methods and
      C. dubliniensis CD36 reference strain. Minimum inhibitory concentrations (MICs)
      were determined using the Clinical and Laboratory Standards Institute standard
      procedure. Time-kill assays were performed using RPMI-1640 as test media over a
      48-h period. AMB proved to be fungicidal at >or=0.5 microg ml(-1) against all
      clinical isolates after 48 h. 5FC was only fungicidal at 32-64x MIC (4-8 microg
      ml(-1)) against all C. dubliniensis isolates. FLC, VRC and POS were fungistatic;
      decrease in colony number was observed only at the highest concentrations tested
      (8, 4 and 4 microg ml(-1), respectively). Triazoles invariably showed fungistatic
      effect at concentrations attainable in the serum. In clinical situations when a
      fungicidal antifungal is desirable, AMB may be used.

PMID- 19761490
TI  - Inhibitory effect of nicotinamide on enzymatic activity of selected fungal
      strains causing skin infection.
AB  - Pathogenicity of fungi is connected with their ability to easily penetrate the
      host tissues, survive in the infected host organism and use the elements of the
      host tissues as nutrients. Hence, the co-occurrence of pathogenic properties with
      the high enzymatic activity, which is manifested through the production of
      various enzymes including extracellular enzymes, was observed. It can be expected
      that it is possible to decrease fungal pathogenicity by lowering their enzymatic
      activity. The aim of the study was to determine the effect of nicotinamide on
      enzymatic activity of the fungi, which are most frequently isolated in cases of
      skin infection. Enzymatic activity was analysed using 15 Candida albicans, 15
      Trichophyton rubrum and 15 Trichophyton mentagrophytes strains. The strains used
      for the study were collected from the current diagnostic material. API ZYM tests
      were used in diagnostic analysis. MICs of nicotinamide were determined by the
      macrodilution method in liquid medium. In the case of Candida strains, the
      presence of nicotinamide in the broth had a significant effect on the decrease of
      enzymatic activity (P < 0.05) of esterase (C4), esterase lipase (C-8), valin
      arylamidase, acid phosphatase and alpha-glycosydase. A considerably stronger
      effect of nicotinamide was observed in the case of dermatophytes (P < 0.005). Its
      action led to a decrease in the activity of all the enzymes under study except
      alpha-glucosidase produced by T. rubrum strains. Thus, nicotinamide exhibited
      biological activity towards C. albicans, T. rubrum and Trichophyton
      mentagrophytes, which resulted in a decrease in the activity of enzymes produced
      by the fungi.

PMID- 19761491
TI  - Constipation: a potential cause of pelvic floor damage?
AB  - BACKGROUND: Pelvic floor damage is a major clinical problem usually attributed to
      obstetric injury. We speculated that constipation may also be an aetiological and
      preventable factor resulting from repeated stress on the perineum over many
      years, and this study aimed to test this hypothesis. METHODS: A total of 600
      women attending a gynaecological clinic were assessed using a structured
      questionnaire gathering data on pelvic floor damage, constipation and obstetric
      trauma. Complete data were available on 596 subjects. KEY RESULTS: The prevalence
      of pelvic floor damage was 10% (61/596). In this group, constipation was
      identified in 31% (19/61) of women and obstetric trauma in 31% (19/61). In the
      group without pelvic floor damage, constipation was present in 16% (86/535) and
      obstetric trauma in 16% (83/535). In univariate analysis, pelvic floor damage was
      associated with age (OR: 1.05; 95% CI: 1.03-1.08; P < 0.0001), constipation (OR:
      2.36; 95% CI: 1.31-4.26; P < 0.0001) and obstetric trauma (OR: 2.46; 95% CI: 1.37
      4.45; P < 0.0028). In multivariate analysis, the OR for age was 1.05 (95% CI:
      1.03-1.08; P < 0.0001), for constipation 2.35 (95% CI: 1.27-4.34; P < 0.0001) and
      for obstetric trauma 1.37 (95% CI: 0.72-2.62; P = 0.3398). CONCLUSIONS &
      INFERENCES: Constipation appears to be as important as obstetric trauma in the
      development of pelvic floor damage. Thus, a more proactive approach to
      recognizing and treating constipation might significantly reduce the prevalence
      of this distressing problem.

PMID- 19761492
TI  - Psychometric performance and clinical meaningfulness of the Patient Assessment of
      Constipation-Quality of Life questionnaire in prucalopride (RESOLOR) trials for
      chronic constipation.
AB  - BACKGROUND: The Patient Assessment of Constipation-Quality of Life (PAC-QOL) is a
      self-reported questionnaire measuring health-related quality of life (HRQL) of
      constipated patients and was used as secondary endpoint in three identical double
      blind, randomized, placebo-controlled Phase III clinical trials. These 12-week
      trials in subjects with severe chronic constipation evaluated the effects of
      prucalopride, a selective 5-HT(4) agonist given orally once daily. METHODS: To
      consolidate the main treatment effect results observed in the prucalopride trial
      populations, analyses were undertaken on the pooled data of the three trials to
      confirm the psychometric properties of the PAC-QOL and to provide guidance for
      the interpretation of the clinical significance of its scores. KEY RESULTS: The
      evaluation of the psychometric properties confirmed the PAC-QOL reliability,
      validity and responsiveness to measure the impact of chronic constipation
      symptoms on HRQL in the prucalopride trials. The 1-point improvement in PAC-QOL
      scores used as target response level for the main treatment effect analyses was
      validated as a relevant definition of response for treatment group comparisons.
      Cumulative distribution curves, drawn for each treatment group to provide more
      complete information on treatment effects than single minimal important
      difference point estimates, demonstrated consistent superior effects of
      prucalopride over placebo on all PAC-QOL scores. CONCLUSIONS & INFERENCES: The
      PAC-QOL questionnaire is a useful measurement tool to assess, from a patient
      perspective, the potential therapeutic value of chronic constipation treatments
      in clinical trials and, by directly reflecting the patient's own perspective on
      constipation and its treatment, eventually also for informing daily medical
      practice.

PMID- 19761493
TI  - Genetically based susceptibility to herbivory influences the ectomycorrhizal
      fungal communities of a foundation tree species.
AB  - Although recent research indicates that herbivores interact with plant-associated
      microbes in complex ways, few studies have examined these interactions using a
      community approach. For example, the impact of herbivory on the community
      structure of ectomycorrhizal fungi (EMF) is not well known. The influence of host
      plant genetics on EMF community composition is also poorly understood. We used a
      study system in which susceptibility to herbivory has a genetic basis and a 20-yr
      insect removal experiment to examine the influence of chronic herbivory and plant
      genetics on the EMF community structure of Pinus edulis. We compared EMF
      communities of herbivore resistant trees, herbivore susceptible trees and
      herbivore susceptible trees from which herbivores were experimentally removed at
      two dates 10 yr apart. In both years sampled, resistant and susceptible trees
      differed significantly in EMF community composition. After 10 yr and 20 yr of
      herbivore removal, the EMF communities of removal trees were similar to those of
      susceptible trees, but different from resistant trees. The EMF community
      composition was more strongly influenced by innate genetic differences in plant
      traits associated with resistance and susceptibility to herbivory than by
      indirect effects of herbivory on host plant relationships with ectomycorrhizal
      fungi.

PMID- 19761494
TI  - Microbiological control of soil-borne phytopathogenic fungi with special emphasis
      on wilt-inducing Fusarium oxysporum.
AB  - Plant diseases induced by soil-borne plant pathogens are among the most difficult
      to control. In the absence of effective chemical control methods, there is
      renewed interest in biological control based on application of populations of
      antagonistic micro-organisms. In addition to Pseudomonas spp. and Trichoderma
      spp., which are the two most widely studied groups of biological control agents,
      the protective strains of Fusarium oxysporum represent an original model. These
      protective strains of F. oxysporum can be used to control wilt induced by
      pathogenic strains of the same species. Exploring the mechanisms involved in the
      protective capability of these strains is not only necessary for their
      development as commercial biocontrol agents but raises many basic questions
      related to the determinism of pathogenicity versus biocontrol capacity in the F.
      oxysporum species complex. In this paper, current knowledge regarding the
      interaction between the plant and the protective strains is reviewed in
      comparison with interactions between the plant and pathogenic strains. The
      success of biological control depends not only on plant-microbial interactions
      but also on the ecological fitness of the biological control agents.

PMID- 19761495
TI  - Structure and biomechanics of trapping flower trichomes and their role in the
      pollination biology of Aristolochia plants (Aristolochiaceae).
AB  - *Catching insects to ensure pollination is one of the most elaborate and
      specialized mechanisms of insect-plant interactions. Phylogenetically,
      Aristolochiaceae represent the first angiosperm lineage that developed trap
      flowers. Here we report the structure and function of specific trichomes
      contributing to the highly specialized trapping devices. *Investigations were
      carried out on six Mediterranean Aristolochia species. The morphology and
      arrangement of the trapping trichomes were investigated by scanning electron
      microscopy (SEM) and cryo-SEM. To demonstrate frictional anisotropy of the
      trapping trichome array, a microtribological approach was used. *The results of
      our experiments support a hypothesis long proposed, but never tested, regarding
      the trapping mechanism in proterogynous Aristolochia flowers: that an array of
      highly specialized trichomes arranged eccentrically to the underlying surface is
      responsible for the easy entrance of insects into flowers but impedes their
      escape. As they enter the male stage of anthesis, flowers significantly modify
      their inner surface characteristics, allowing insects to leave. *We have
      demonstrated the substantial contribution of trapping trichomes to the capture,
      retention and release of pollinators, an important prerequisite for making cross
      pollination possible in most Aristolochia species. Finally, we compare trapping
      trichomes of Aristolochia with similar structures found in other trapping flowers
      as well as in pitchers of carnivorous plants not optimized for insect release.

PMID- 19761496
TI  - The influence of species and growing conditions on the 18-O enrichment of leaf
      water and its impact on 'effective path length'.
AB  - The stable oxygen isotope ratio (delta(18)O) of plant material has been shown to
      contain essential information on water and carbon fluxes at the plant and
      ecosystem scales. However, the effective path length (L(m)), a parameter
      introduced to leaf-water models still requires a comprehensive biological
      characterization to allow interpretation of delta(18)O values in plant material
      with confidence. Here, we tested the variability of L(m) across and within three
      species that developed leaves in environments with different relative humidity.
      We also tested whether the L(m) of fully developed leaves is affected by short
      term fluctuations in relative humidity. We determined that significant
      differences in L(m) exist among Phaseolus vulgaris, Rizinus communis and
      Helianthus annuus. Within a given species, however, L(m) values did not differ
      significantly among individuals. These findings indicate that L(m) is species
      specific and a relatively constant parameter and that L(m) will not obscure the
      interpretation of delta(18)O values in plant material of a given species. We urge
      caution, however, because values for L(m) are derived from fitting leaf-water
      models to measured values of delta(18)O, so care must be taken in assigning a
      'cause' to values of L(m) as they likely capture a combination of different
      biological leaf properties.

PMID- 19761498
TI  - Uvular abnormalities in patients with submucous fibrosis.

PMID- 19761497
TI  - Oxidant/antioxidant status in recurrent aphthous stomatitis.
AB  - OBJECTIVE: Recurrent aphthous stomatitis (RAS) is a common oral mucosal disorder
      characterized by recurrent, painful oral aphthae, and oxidative stress presumably
      contributes to its pathogenesis. The study was performed to evaluate the
      involvement of oxidant toxicity in this disorder. METHODS: Patients with RAS (n =
      26) and age- and sex-matched healthy control subjects (n = 20) were included in
      this study. Following an overnight fast, blood specimens were obtained. Plasma
      malondialdehyde concentrations and erythrocytes glutathione peroxidase activities
      were determined. Also, plasma vitamin E and selenium levels were detected. Mann
      Whitney U-test was performed for statistical evaluation. RESULTS: Oxidative
      stress was confirmed by the significant elevation in plasma malondialdehyde
      levels and by the significant decrease in glutathione peroxidase activities,
      vitamin E and selenium levels (P < 0.001). CONCLUSIONS: Our results indicated
      that lipid peroxidation and the inadequacy of the defense system seem to play a
      crucial role in the pathogenesis of recurrent aphthous stomatitis.

PMID- 19761499
TI  - Marathon of eponyms: 5 Ehlers-Danlos syndrome.
AB  - The use of eponyms has long been contentious, but many remain in common use, as
      discussed elsewhere (Editorial: Oral Diseases. 2009: 15; 185). The use of eponyms
      in diseases of the head and neck is mainly in specialties dealing with medically
      compromised individuals (paediatric dentistry, special care dentistry, oral and
      maxillofacial medicine, oral and maxillofacial pathology, oral and maxillofacial
      radiology and oral and maxillofacial surgery) and particularly by hospital
      centred practitioners. This series has selected some of the more recognized
      relevant eponymous conditions and presents them alphabetically. The information
      is based largely on data available from MEDLINE and a number of internet websites
      as noted below: the authors would welcome any corrections. This document
      summarizes data about Ehlers-Danlos syndrome.

PMID- 19761500
TI  - Difference in conduction velocity and amplitude of electrograms in "in situ" and
      "isolated-perfused" canine hearts: what could be the reason?

PMID- 19761501
TI  - Paradoxical extranodal response during para-Hisian pacing: what is the mechanism?

PMID- 19761502
TI  - Increased defibrillator charge time following direct trauma to an ICD generator:
      blunt consequences.

PMID- 19761503
TI  - Atrial tachycardia with atypical Wenckebach atrioventricular block after slow
      pathway ablation.
AB  - A case of a patient with dual supraventricular tachycardias, atrioventricular
      nodal tachycardia, and atrial tachycardia is presented. The former was
      successfully ablated, whereas the latter was inducible after the ablation of the
      former, but without clinical importance during follow-up. However, this
      tachycardia showed interesting characteristics, including dual atrioventricular
      Wenckebach periodicity, presumably due to multiple slow pathways.

PMID- 19761504
TI  - ATP revealed extra pulmonary vein source of atrial fibrillation after
      circumferential pulmonary vein isolation.
AB  - Noninducibility of atrial fibrillation (AF) by additional electrograms-guided
      ablation may benefit the clinical outcome. This report illustrates the effect of
      adenosine triphosphate (ATP) injection on AF inducibility after pulmonary vein
      (PV) isolation. AF was triggered twice by ATP without PV reconnection. Meanwhile,
      complex fractionated atrial electrograms (CFAEs) were observed, and ablation
      targets on these sites appeared to be essential to the AF elimination. It
      suggests that CFAEs may contribute to the initiation of some AF. ATP may be
      useful to induce AF after proven PV isolation, and further ablation might be
      necessary to ensure efficacy after circumferential PV isolation.

PMID- 19761505
TI  - Slow conduction within lateral myocardial scar and response to cardiac
      resynchronization therapy.
AB  - Cardiac resynchronization therapy (CRT) improves symptoms and survival in some
      selected heart failure patients. However, around 30% of patients still do not
      respond to CRT. In these patients, methodological approach of any potential cause
      of nonresponse should be reviewed. We describe the case of limited left ventricle
      (LV) myocardium capture by LV lead during biventricular pacing secondary to a
      slow conduction from LV lead impulse, located in a scar zone, and the benefit of
      interventricular delay optimization in this setting. This case emphasizes the
      interest of considering 12-lead electrocardiogram during management of patients
      with CRT.

PMID- 19761506
TI  - Incremental changes in QRS duration predict mortality in patients with atrial
      fibrillation.
AB  - BACKGROUND: The purpose of this study was to evaluate serial changes in QRS
      duration in the 12-lead electrocardiogram (ECG) and their prognostic value in
      patients with atrial fibrillation (AF). METHODS: Retrospective evaluation of the
      12-lead ECG was performed in 822 patients with AF. Inclusion criteria included AF
      in two sequential ECGs and an echocardiogram obtained within 7 days of the second
      ECG. The mean age of the 228 patients enrolled in the study was 71.2+/-12.9 and
      45.6% were females. Nearly half of the patients had hypertension (49.5%) and a
      history of heart failure (44.7%). The patients were followed for 21+/-19 months,
      and the end point was all-cause mortality. RESULTS: Cox proportional hazards
      analysis demonstrated that the independent predictors of mortality in AF patients
      were age, renal insufficiency, a history of stroke, heart rate, incremental QRS
      prolongation (P=0.0418), and the absence of warfarin use. Patients with QRS
      prolongation>15 ms had a worse prognosis than those with QRS prolongation<or=15
      ms (P=0.0019). CONCLUSIONS: A progressive increase in QRS duration predicted a
      poor prognosis in patients with AF in our study. A prospective study is needed to
      substantiate the prognostic value of QRS prolongation in AF patients.

PMID- 19761507
TI  - Relative changes in resting energy expenditure during weight loss: a systematic
      review.
AB  - A more comprehensive understanding of the effects of weight loss on the changes
      in resting energy expenditure (EE) is relevant. A MEDLINE search was performed to
      identify studies with information relevant to this systematic review. From this
      search, the mean rate of resting EE decrease relative to weight loss was
      calculated from 90 available publications. A decrease of resting EE relative to
      weight loss of -15.4 +/- 8.7 kcal kg(-1) was observed from 2977 [corrected]
      subjects. No sex differences were noted in the overall resting EE decrease
      relative to weight loss. However, a significant sex differences was seen with
      pharmacological interventions, which seemed to depress the resting EE relative to
      weight loss to a greater extent in men than in women (P < 0.05). A greater drop
      in resting EE relative to weight loss was observed for short interventions (more
      than 2 but less than 6 weeks) when compared with long interventions (<6 weeks) (
      27.7 +/- 6.7 vs. -12.8 +/- 7.1 kcal kg(-1)) (P < 0.001). Men and women have a
      similar decrease in resting EE relative to weight loss except in the case of
      pharmacological interventions. Short interventions also produced greater resting
      EE losses relative to weight loss.

PMID- 19761508
TI  - A national survey of the prevalence of childhood overweight and obesity in Italy.
AB  - To estimate the prevalence of childhood overweight and obesity among Italian
      schoolchildren and to examine geographic differences and present and future
      implications for health care, we used data from a nationwide representative
      survey performed in May 2008 among third-grade students in 18 of Italy's 21
      regions. Cluster sampling was used to identify classes for participation. The
      study population included all children aged 8-9 years whose parents agreed to opt
      out consent. Parents, children and teachers completed brief questionnaires, and
      children were weighed and measured by trained staff using standardized equipment.
      Consent was obtained for 97% of 50 197 third-graders, of whom 44 676 (89%) met
      study inclusion criteria. Obesity levels (defined using International Obesity
      Task Force cut-offs) ranged from 7.5% (95% confidence intervals 6.7-8.2) in the
      north to 16.6% (95% confidence intervals 15.8-17.4) in the south. Behaviours
      known to be associated with obesity also showed geographic differences. The
      estimated burden of obesity-related pathologies also increased from north to
      south. These findings suggest the need for community as well as individual
      interventions in all areas of the country but with particular attention to the
      south.

PMID- 19761509
TI  - Anesthetic-induced neurotoxicity of the neonate: time for clinical guidelines?

PMID- 19761510
TI  - Anesthesia for children with hyperleukocytosis a retrospective review.
AB  - BACKGROUND: Hyperleukocytosis (a white cell count in peripheral blood >100 x
      10(9) l(-1)) is a well-recognized medical emergency. Rates of morbidity
      associated with anesthesia in hyperleukocytotic patients have not been previously
      described. This retrospective study describes the perioperative morbidity and
      mortality of children who present acutely with hyperleukocytosis. METHODS: All
      patients under 17 years of age with leukemia complicated by hyperleukocytosis and
      who received general anesthesia as part of their acute care at the Children's
      Hospital in Westmead from July 1999 to June 2008 were included. Data describing
      perioperative adverse events within 48 h of anesthesia were collected using a
      systematic chart review. RESULTS: Over the 8- year period, 60 children were
      admitted with hyperleukocytosis related to a new diagnosis of leukemia. Fifty-two
      children had general anesthesia within 48 h of their admission. Eleven children
      required two separate general anesthetics within this same time frame. Two deaths
      were recorded within 48 h of anesthesia; one child died from neurological
      complications of her disease, and the second died from multi-organ failure. Three
      children had serious respiratory adverse events requiring postanesthesia
      intensive care. Thirteen children had notable but less serious adverse events.
      These were typically respiratory in nature and required supplemental oxygen for
      more than 2 h after anesthesia. CONCLUSION: Children with leukemia-related
      hyperleukocytosis often require general anesthesia at the time of presentation
      and are at significant perioperative risk. Respiratory adverse events are very
      common and mandate close postanesthesia care.

PMID- 19761511
TI  - CD14 polymorphisms in mother and infant, soluble CD14 in breast milk and atopy
      development in the infant (KOALA Study).
AB  - Different CD14 polymorphisms have been associated with atopic phenotypes in
      infants. In addition, CD14 genotypes of breastfeeding mothers have been
      associated with soluble CD14 (sCD14) levels in breast milk. The role of CD14
      genotypes of infant and mother and their interaction with sCD14 levels in breast
      milk in atopy development remain to be established. We aimed to study the
      associations of CD14 single nucleotide polymorphisms (SNPs), and their
      interaction with breast milk sCD14, with atopy development until age two. In
      addition, we assessed whether levels of sCD14 in breast milk associated with SNPs
      in CD14. Four SNPs in CD14 gene were investigated in 698 infants and 188 mothers.
      Associations between these SNPs, sCD14 and atopy development were analyzed in
      multiple logistic or linear regression models. The CD14/-1619 SNP was associated
      with eczema. CC homozygotes showed a lower risk of eczema vs. TT homozygotes
      (adjusted odds ratio = 0.56, 95% confidence interval 0.33-0.96) in a co-dominant
      model. Breast milk sCD14 levels did not significantly modify the effect of the
      child's CD14 genotype on atopy development (p interaction > or =0.10). Maternal
      CD14 SNPs were not significantly associated with sCD14 levels in breast milk
      (anova, p > or = 0.48). We found only an association between CC homozygozity of
      SNP CD14/-1619 and eczema. Our data did not support a modifying role of breast
      milk sCD14 levels on the relationship between CD14 genotype and atopy development
      until age 2 yr.

PMID- 19761512
TI  - The vertebral artery is unlikely to be the sole source of vascular complications
      occurring during stellate ganglion block.
AB  - INTRODUCTION: Stellate ganglion block (SGB) is commonly performed for upper
      extremity complex regional pain syndrome and other conditions. Known
      complications of stellate block include Horner's syndrome, hoarseness, hematoma
      formation, airway compromise, immediate seizure (presumably from vertebral artery
      injection), and death. A previous arterial anatomy study demonstrated other
      vessels, eg, the ascending and deep cervical arteries, reinforcing the blood
      supply of the spinal cord and brain stem. The potential role of these vessels in
      the pathogenesis of seizures or hematoma during SGB has not been studied.
      METHODS: The anatomical recording log from 10 cadaver dissections and
      photographic records of same were reviewed to ascertain the presence of the
      ascending or deep cervical arteries, or other branches emanating from the
      thyrocervical or costocervical trunk and their relationship to the medial
      anterior surface of the C6 and C7 transverse processes. RESULTS: In 4 cases, as
      determined by the dissection log, and in 6 cases, determined by photographic
      images, the ascending cervical artery or a branch from the thyrocervical trunk
      passed over the anterior aspect of the transverse processes of C6 or C7.
      DISCUSSION: Arterial vessels other than the vertebral artery that also supply the
      anterior spinal cord and brain stem pass directly anterior to the transverse
      processes at the most common sites of the SGB. It is anatomically possible,
      therefore, that accidental injection or induced spasm of these vessels and not
      the vertebral arteries is responsible for some cases of seizure, hematoma, or
      other vascular complications during SGB.

PMID- 19761513
TI  - Ultrastructural changes in axons following exposure to pulsed radiofrequency
      fields.
AB  - Pulsed radiofrequency (PRF) fields applied by an electrode to neural structures,
      such as the peripheral sensory nociceptor axons and dorsal root ganglion, are
      clinically effective in reducing pain and other neuropathic syndromes. However, a
      full understanding of the underlying mechanisms by which this occurs has not yet
      been clarified. In this study, PRF is applied to the afferent axons of the
      sciatic nerves of rats. A standard radiofrequency (RF) electrode and RF generator
      is used to apply the RF signal output to the sciatic nerve using standard PRF
      parameters that have been successfully used in clinical practice. The
      ultrastructure of the treated axons is observed after 10 days by electron
      microscopy. A control, sham application is simultaneously applied to the
      contralateral sciatic nerve to provide a statistical differential comparison. It
      is found that the internal ultrastructural components of the axons show
      microscopic damage after PRF exposure, including: abnormal membranes and
      morphology of mitochondria, and disruption and disorganization of microfilaments
      and microtubules. The damage appears to be more pronounced for C-fibers than for
      A-delta and A-beta fibers. The results are discussed in terms of internal
      electric field strengths and thermodynamic parameters.

PMID- 19761514
TI  - Impact of massage therapy on motor outcomes in very low-birthweight infants:
      randomized controlled pilot study.
AB  - BACKGROUND: The purpose of the present study was to determine the effects of
      massage therapy on motor development, weight gain, and hospital discharge in
      preterm very low-birthweight (VLBW) newborns. METHODS: Twenty-four preterm VLBW
      newborns (<34 weeks and <1500 g) were enrolled in this randomized controlled
      pilot study. The intervention group (n = 12) received massage therapy starting at
      34 weeks post-conceptional age (15 min daily, 5 days/week for 4 weeks). The
      infants in the sham treatment group (n = 12) received similar duration of light
      still touch. Test of Infant Motor Performance (TIMP) score gain, weight gain, and
      post-conceptional age at discharge were compared between the two groups after
      intervention using Mann-Whitney U-test. RESULTS: No significant between-group
      difference in TIMP score gain and weight gain was identified when all subjects
      were analyzed. In subgroup analysis, among those with below-average pre-treatment
      TIMP score (<35), the intervention group (n = 6) achieved significantly higher
      TIMP score gain (P = 0.043) and earlier hospital discharge (P = 0.045) than the
      sham treatment group (n = 5). These same infants, however, also had significantly
      shorter duration of total parenteral nutrition than their counterparts in the
      sham treatment group (P = 0.044). CONCLUSIONS: Massage therapy might be a viable
      intervention to promote motor outcomes in a subgroup of VLBW newborns with poor
      motor performance. A larger randomized controlled trial is required to further
      explore the effects of massage therapy in this high-risk group.

PMID- 19761515
TI  - Early use of probiotics is important therapy in infants with severe congenital
      anomaly.
AB  - BACKGROUND: Infants with severe congenital anomaly often need to undergo
      operation followed by antibiotic therapy. As a result they inevitably acquire
      abnormal intestinal microbiota, which cause severe infections such as necrotizing
      enterocolitis. Also, intestinal function deteriorates and their nutritional state
      is very poor. In order to prevent these situations probiotic therapy is proposed
      as an effective supporting treatment. Probiotic therapy were therefore applied to
      infants with severe congenital anomaly as early as possible to ascertain its
      efficacy. METHODS: As probiotics, two bacteria were used: Bifidobacterium breve
      Yakult and Lactobacillus casei Shirota. Probiotic therapy was used in four
      infants with severe congenital anomaly as early as possible after surgery. Their
      intestinal microbiota and physical growth were followed through the treatment
      course. RESULTS: Two patients suffered from meconium peritonitis with ileal
      atresia. One patient was born with complex anomalies (omphalocele, bladder
      exstrophy, myelomeningocele). The fourth patient suffered from complete urorectal
      septum malformation. The intestinal microbiota of these four patients was first
      induced to be probiotic dominant and finally changed to commensal anaerobe
      dominant that was similar to normal intestinal microbiota. Pathogenic bacteria
      were seldom detected. The patients' physical growth was excellent despite short
      bowel and pulmonary hypoplasia. CONCLUSION: Probiotic therapy was effective in
      inducing probiotic dominant intestinal microbiota and normal intestinal
      microbiota in infants with severe congenital anomalies. As a result their
      intestinal absorptive functions were activated and severe infections were
      completely prevented. All of the infants grew well despite their physical
      disadvantages.

PMID- 19761516
TI  - Survey of severe respiratory syncytial virus infection in Kyoto Prefecture from
      2003 to 2007.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) infection in infants can develop
      into a severe condition. METHODS: A survey of patients with severe RSV infection
      in hospitals in Kyoto Prefecture was performed from 2003 to 2007. Patients
      requiring intubation and those with cardiopulmonary arrest on arrival (CPAOA)
      were considered to have severe RSV infection. RESULTS: Twenty-five patients with
      severe infection were identified and detailed data were available for 21
      patients, of whom 18 required intubation and three had CPAOA. The male/female
      ratio was 12/9 and age ranged from 8 days to 19 years (average, 5.2 months;
      median: 2 months). At admission white blood cell count, lactate dehydrogenase (P
      < 0.05), and blood glucose (P < 0.01) were higher and Na was lower (P < 0.01) in
      the 18 patients with severe infection (excluding the CPAOA cases) compared to 18
      sex- and age-matched patients with mild RSV infection. The incidence of bacterial
      infection was also higher in severe cases (P < 0.05). The outcome was death in
      four patients (19.0%, including two sudden deaths), aftereffects in two (9.5%),
      hospital discharge with improvement in 14 (66.7%), and an unclear outcome in one
      patient. Excluding the two sudden death cases, 14 of 19 patients (73.7%) were
      extubated within 2 weeks. The period of intubation was longer in older patients
      (P < 0.05). CONCLUSION: Because severe RSV infection led to sudden death in two
      cases, detection of RSV is important at admission for an infant with CPAOA.
      Fourteen patients (66.7%), however, had good outcomes and most patients were
      extubated within 2 weeks.

PMID- 19761517
TI  - Serum indoxyl sulfate as an early marker for detecting chronic cyclosporine
      nephrotoxicity.
AB  - BACKGROUND: Cyclosporine A (CsA) is an effective agent for frequently relapsing
      steroid-dependent nephrotic syndrome (FR-SDNS), but its use can also be
      complicated by renal toxicity. Because no biochemical markers from urine or blood
      samples have yet been established for detecting CsA-induced renal injury to date,
      repeated renal biopsies are therefore required for all patients with long-term
      CsA treatment. The purpose of the present study was therefore to detect early
      change of CsA nephropathy (CsAN) using blood samples. METHODS: Several
      biochemical markers were analyzed in an attempt to examine the renal function in
      24 patients with FR-SDNS who had been treated with CsA. Those included serum
      cystatin C and indoxyl sulfate, as well as creatinine and beta2-microglobulin.
      RESULTS: Renal biopsy findings indicated chronic CsAN in 13 of the 24 patients.
      Among those markers, only serum indoxyl sulfate was significantly elevated in
      patients with CsAN. CONCLUSIONS: It may be possible for measurement of serum
      indoxyl sulfate level to replace repeated renal biopsies in evaluation of chronic
      CsAN in pediatric patients with FR-SDNS.

PMID- 19761518
TI  - Interlimb coordination differentiates Brazilian children from two socioeconomic
      settings.
AB  - BACKGROUND: The aim of the present study was to test the notion that Brazilian
      children entering private school have a motor function advantage over those
      entering their first year in public school. METHODS: Four hundred and two
      children from the two cultural settings were examined for motor function in the
      first and 10th month of school (first grade). Participants were assessed based on
      age-level standards and by total score for all items for children 3 to 7 years of
      age. RESULTS: The private school group outperformed their public setting peers on
      the first and second assessment; both groups improved over the school year. The
      most interesting outcome was the type of motor task that most clearly
      differentiated the groups: activities requiring gross motor (interlimb)
      coordination. CONCLUSION: Among the recommendations given, it is suggested that
      motor skill activities, especially those involving interlimb coordination, be
      included with any type of motor programming for young children.

PMID- 19761519
TI  - Effect of retinoic acid on renal development in newborn mice treated with an
      angiogenesis inhibitor.
AB  - BACKGROUND: A mouse model of impaired renal development was developed and the
      effect of retinoic acid (RA) was investigated in this animal model. METHODS: An
      angiogenesis inhibitor (SU1498) was injected s.c. into day 3 C57BL/6 newborn mice
      to create a model of arrested renal development. RA (2 mg/kg) was injected i.p.
      for 10 days. Morphometry and immunohistochemistry were done. RESULTS: Mice
      injected with SU1498 demonstrated deranged renal development in tubular structure
      and glomerular tuft area. Cortical thickness and area of glomerular tuft were
      significantly decreased after vascular endothelial growth factor (VEGF)
      inhibitor, and were significantly restored by RA. The length of capillary
      loops/glomerulus, the number of podocytes/glomerulus, and density of peritubular
      capillaries on CD31 immunostaining were significantly decreased by VEGF blocking
      and recovered by RA. CONCLUSIONS: VEGF plays a major role in renal development,
      and RA reverses the inhibited development caused by an angiogenesis inhibitor.

PMID- 19761520
TI  - Keratinocytes in culture accumulate phagocytosed melanosomes in the perinuclear
      area.
AB  - There are many techniques for evaluating melanosome transfer to keratinocytes but
      the spectrophotometric quantification of melanosomes incorporated by keratinocyte
      phagocytosis has not been previously reported. Here we describe a new method that
      allows the spectrophotometric visualization of melanosome uptake by normal human
      keratinocytes in culture. Fontana-Masson staining of keratinocytes incubated with
      isolated melanosomes showed the accumulation of incorporated melanosomes in the
      perinuclear areas of keratinocytes within 48 h. Electron microscopic observations
      of melanosomes ingested by keratinocytes revealed that many phagosomes containing
      clusters of melanosomes or their fragments were localized in the perinuclear
      area. A known inhibitor of keratinocyte phagocytosis which inhibits protease
      activated receptor-2, i.e., soybean trypsin inhibitor, decreased melanosome
      uptake by keratinocytes in a dose-dependent manner. These data suggest that our
      method is a useful model to quantitate keratinocyte phagocytosis of melanosomes
      visually in vitro.

PMID- 19761521
TI  - Evaluating two-step PCA of ERP data with Geomin, Infomax, Oblimin, Promax, and
      Varimax rotations.
AB  - Principal components analysis (PCA) can facilitate analysis of event-related
      potential (ERP) components. Geomin, Oblimin, Varimax, Promax, and Infomax
      (independent components analysis) were compared using a simulated data set. Kappa
      settings for Oblimin and Promax were also systematically compared. Finally, the
      rotations were also analyzed in a two-step PCA procedure, including a contrast
      between spatiotemporal and temporospatial procedures. Promax was found to give
      the best overall results for temporal PCA, and Infomax was found to give the best
      overall results for spatial PCA. The current practice of kappa values of 3 or 4
      for Promax and 0 for Oblimin was supported. Source analysis was meaningfully
      improved by temporal Promax PCA over the conventional windowed difference wave
      approach (from a median 32.9 mm error to 6.7 mm). It was also found that
      temporospatial PCA produced modestly improved results over spatiotemporal PCA.

PMID- 19761522
TI  - Resource allocation and fluid intelligence: insights from pupillometry.
AB  - Thinking is biological work and involves the allocation of cognitive resources.
      The aim of this study was to investigate the impact of fluid intelligence on the
      allocation of cognitive resources while one is processing low-level and high
      level cognitive tasks. Individuals with high versus average fluid intelligence
      performed low-level choice reaction time tasks and high-level geometric analogy
      tasks. We combined behavioral measures to examine speed and accuracy of
      processing with pupillary measures that indicate resource allocation. Individuals
      with high fluid intelligence processed the low-level choice reaction time tasks
      faster than normal controls. The task-evoked pupillary responses did not differ
      between groups. Furthermore, individuals with high fluid intelligence processed
      the high-level geometric analogies faster, more accurately, and showed greater
      pupil dilations than normal controls. This was only true, however, for the most
      difficult analogy tasks. In addition, individuals with high fluid intelligence
      showed greater preexperimental pupil baseline diameters than normal controls.
      These results indicate that individuals with high fluid intelligence have more
      resources available and thus can solve more demanding tasks. Moreover, high fluid
      intelligence appears to be accompanied by more task-free exploration.

PMID- 19761523
TI  - Countermeasure mechanisms in a P300-based concealed information test.
AB  - We recently introduced an accurate and countermeasure (CM)-resistant P300-based
      deception detection test (J.P. Rosenfeld et al., 2008). When subjects use CMs to
      all irrelevant items in the test, the probe P300 is increased rather than
      reduced, as in previous P300-based deception protocols, allowing detection of CM
      users. Evidence herein suggests this is partly due to an omit effect; the probe
      was the only uncountered item. Three groups were tested: a guilty omit probe
      group performed an explicit response to each irrelevant item but not to the
      probe, an innocent omit irrelevant group saw only irrelevant items and omitted a
      response to one item, and a guilty no omit group had a concealed information item
      as probe and performed an explicit response to each. We found a greater P300
      amplitude to probes in the guilty omit probe condition as compared with the other
      two conditions, indicating a P300 enhancing effect of omitting a response to a
      single stimulus.

PMID- 19761524
TI  - The effects of smoking on selective attention as measured by startle reflex, skin
      conductance, and heart rate responses to auditory startle stimuli.
AB  - The present study examined the effects of cigarette smoking on attentional
      processing by measuring nondeprived smokers' (n=39), minimally deprived smokers'
      (n=36), and nonsmokers' (n=34) startle eyeblink reflex, heart rate, and skin
      conductance responses (SCR) to acoustic startle stimuli (105 dB) during directed
      attention tasks. Whereas smokers demonstrated smaller startle responses than
      nonsmokers during a directed attention visual task, no difference in startle
      response magnitude emerged between the two smoking groups, nor did we observe an
      effect of smoking on SCR or heart rate response to the startle stimuli. Our
      findings suggest that smokers differ from nonsmokers in their selective attention
      abilities and that smoking does not enhance minimally deprived smokers' selective
      attention.

PMID- 19761525
TI  - The effect of face inversion on intracranial and scalp recordings of event
      related potentials.
AB  - The face inversion effect (FIE) refers to a disproportionate disruption of the
      processing of face information by inverting faces. We investigated the FIE in
      epilepsy patients by simultaneous intracranial and scalp recordings of event
      related potentials (ERPs). In scalp recordings, a typical FIE on ERPs was
      observed with increased latencies and amplitudes of the positive counterpart of
      the occipito-temporal N170, namely, the vertex positive potential (VPP), in
      response to inverted faces. Similar amplitude and latency increases were revealed
      for the intracranial N200 recorded over face-sensitive and non-face-sensitive
      areas in the lateral occipital cortex, but not in the ventral temporal cortex.
      Peak latencies did not differ between the scalp VPP and intracranial N200.
      Findings indicate that the lateral occipital cortex but not the ventral temporal
      cortex contributes primarily to the FIE observed in scalp recordings.

PMID- 19761526
TI  - Novelty P3 reductions in depression: characterization using principal components
      analysis (PCA) of current source density (CSD) waveforms.
AB  - We previously reported a novelty P3 reduction in depressed patients compared to
      healthy controls (n=20 per group) in a novelty oddball task using a 31-channel
      montage. In an independent replication and extension using a 67-channel montage
      (n=49 per group), reference-free current source density (CSD) waveforms were
      simplified and quantified by a temporal, covariance-based principal components
      analysis (PCA) (unrestricted Varimax rotation), yielding factor solutions
      consistent with other oddball tasks. A factor with a loadings peak at 343 ms
      summarized the target P3b source as well as a secondary midline frontocentral
      source for novels and targets. An earlier novelty vertex source (NVS) at 241 ms
      was present for novels, but not targets, and was reduced in patients. Compatible
      CSD-PCA findings were also confirmed for the original low-density sample. Results
      are consistent with a reduced novelty response in clinical depression, involving
      the early phase of the frontocentral novelty P3.

PMID- 19761527
TI  - Successful treatment of severe subcutaneous insulin resistance with inhaled
      insulin therapy.
AB  - The potential of inhaled insulin therapy for severe resistance to subcutaneous
      insulin was tested in a 7-yr old boy with type 1 diabetes mellitus. The
      efficiency of 1 mg inhaled insulin (Exubera) was examined by a 4-h euglycemic
      clamp study. During the clamp, the glucose infusion rate started to increase 25
      min after inhalation and peaked 120 min after inhalation. Subsequently, a trial
      of inhaled insulin monotherapy was initiated consisting of pre-meal inhalations
      and one inhalation during the night. Since glycemic control remained fair (HbA1c
      approximately 8.5%), this therapy was continued. Over the ensuing 18 months, mild
      keto-acidosis occurred twice during gastro-enteritis. Inhaled insulin was well
      tolerated and pulmonary function did not deteriorate. We conclude that severe
      resistance to subcutaneous insulin does not preclude sufficient absorption of
      insulin delivered by pulmonary.

PMID- 19761528
TI  - Risk markers of future microalbuminuria and hypertension based on clinical and
      morphological parameters in young type 1 diabetes patients.
AB  - BACKGROUND: Nephropathy is a severe complication of type 1 diabetes and develops
      in 30% of patients. Currently, it is not possible to identify young patients at
      risk prior to the development of microalbuminuria (MA) and/or hypertension (HT).
      OBJECTIVE: To study predictors of MA and/or HT in young normoalbuminuric (NA)
      patients with type 1 diabetes. SUBJECTS AND METHODS: Forty-six NA and
      normotensive (NT) type 1 diabetes patients, regularly followed since onset with
      checks on metabolic control, kidney function, and MA, were investigated with
      kidney biopsies and 24-h ambulatory blood pressure measurements (ABPMs) after
      10.6 yr of diabetes. The patients were followed another six and a half years with
      regard to the development of MA and HT. RESULTS: Fifteen patients developed MA
      and/or HT during follow-up. The strongest risk markers were poor metabolic
      control after puberty, high day-time systolic blood pressure (BP), and increased
      BMT at 10 yr, which explained 62% of the outcome for MA and/or HT at 17 yr
      duration with 77% sensitivity and 65% specificity. The threshold values were long
      term postpubertal HbA(1c) > 8.2%, day-time systolic BP > 130 mmHg, and BMT > 490
      nm/1.73 m(2). CONCLUSIONS: Normoalbuminuric and NT patients at risk of developing
      MA and HT could be identified and might benefit from an early start of
      antihypertensive therapy and improvement of metabolic control.

PMID- 19761529
TI  - Sociodemographic and psychosocial factors associated with continuous subcutaneous
      insulin infusion in adolescents with type 1 diabetes.
AB  - OBJECTIVE: To examine the role of sociodemographic factors and psychosocial
      adjustment in continuous subcutaneous insulin infusion (CSII) use among
      adolescents with type 1 diabetes. METHODS: A total of 150 adolescents with type 1
      diabetes and their caregivers completed measures of general psychological
      functioning, diabetes functioning, and stressful life events. Blood glucose
      monitoring (BGM) frequency and glycemic control were also assessed. Logistic
      regression was used to determine associations between CSII use and
      sociodemograpic and psychosocial factors. RESULTS: All logistic regression models
      were significant, indicating a large proportion of the variance in CSII use was
      associated with sociodemographic, diabetes-specific and psychosocial variables.
      Final models showed higher frequency of BGM and having private insurance as
      significant correlates of CSII use. CSII use was also associated with adolescent
      and caregiver reports of sharing of responsibilities around diabetes management
      and negative affect regarding BGM. CONCLUSIONS: Adolescents currently prescribed
      CSII therapy evidenced key differences from their counterparts using multiple
      daily injections (MDI) in insurance status, diabetes management behavior, and
      family functioning related to diabetes. Efforts to understand the role of family
      factors in the maintenance of CSII therapy with clinical indicators of CSII use
      may inform treatment effectiveness.

PMID- 19761530
TI  - Daily vegetable intake during pregnancy negatively associated to islet
      autoimmunity in the offspring--the ABIS study.
AB  - OBJECTIVE: To investigate if maternal diet during pregnancy is associated with
      occurrence of islet autoimmunity (IA) in the offspring. METHODS: Of 21 700
      infants invited to the All Babies in South-east Sweden (ABIS) study, 16 004
      screening questionnaires, including a 22-item food frequency questionnaire (FFQ)
      regarding the mothers' diet during pregnancy, were completed after delivery.
      Follow-up of the children (questionnaires and blood sampling) was performed at 1,
      2.5 and 5 yr of age. IA was defined as being positive (above the 95th percentile
      for healthy children) in two or more measurements of autoantibodies [glutamic
      acid decarboxylase (GADA); tyrosine phosphatase (IA-2A), insulin autoantibodies
      (IAA)] analysed at the three time points or being diagnosed with type 1 diabetes
      during the 5-yr follow-up period. The 5 724 children in whom we carried out two
      to three possible blood samplings were included in the study. Logistic regression
      analysis was used to identify variables predicting IA. RESULTS: Of 5 724
      children,191 (3.3%) were considered positive for IA. In a univariate analysis,
      less than daily consumption of vegetables (3-5 times/week) in the mothers' diet
      was associated with increased risk of IA (OR 1.71, 95% CI:1.24-2.35, p = 0.001)
      compared to daily consumption (p for trend = 0.004). The association was
      strengthened when adjusting for known IA-risk factors (p for trend <0.001).
      CONCLUSIONS: Daily consumption of vegetables in the mothers' diet during
      pregnancy was associated with a decreased risk of IA in the offspring.

PMID- 19761531
TI  - Ion, protein, phospholipid and energy substrate content of oviduct fluid during
      the oestrous cycle of buffalo (Bubalus bubalis).
AB  - The aim of this research was to analyse the composition of oviduct fluid (ODF) in
      buffalo cows at different oestrous cycle phases to fulfil the requirements of
      buffalo embryos in vitro. ODF was collected by chronic cannulation from three
      cows that were synchronized by administering a synthetic prostaglandin. Based on
      hormonal profiles, the pre-ovulatory, ovulatory, post-ovulatory and luteal phases
      of the oestrous cycle were defined. The volume of ODF produced (ml/24 h) was
      influenced by the oestrous cycle, with values (mean +/- SE) around ovulation (1.0
      +/- 0.2) greater (p < 0.05) than in both the luteal (0.4 +/- 0.1) and the post
      ovulatory phases (0.5 +/- 0.1), but not different from the intermediate values in
      the pre-ovulatory phase (0.8 +/- 0.2). Among cycle phases, no differences were
      found in sodium, potassium, calcium and magnesium concentrations (130.0 +/- 1.1,
      5.1 +/- 0.3, 2.8 +/- 0.1 and 0.59 +/- 0.04 mmol/l respectively). Interestingly,
      the chloride secretion (MUm/24 h) was higher (p < 0.05) at ovulation (150.2 +/-
      16.5) than during both the luteal (73.7 +/- 22.0) and the post-ovulatory phases
      (63.7 +/- 11.2), with intermediate values in the pre-ovulatory phase (113.4 +/-
      23.5). Glucose concentration (mmol/l) was higher (p = 0.056) in the pre-ovulatory
      phase (0.06 +/- 0.02) than in the luteal (0.02 +/- 0.01) and post-ovulatory (0.02
      +/- 0.01) phases but not different from values in the ovulatory phase (0.04 +/-
      0.02). Concentrations of pyruvate and lactate among oestrous cycle phases were
      similar (0.08 +/- 0.01 and 1.0 +/- 0.1 mmol/l respectively). The total quantity
      of phospholipids (MUmol/24 h) was greater (p < 0.05) at ovulation (0.21 +/- 0.02)
      compared with the luteal, pre-ovulatory and post-ovulatory phases of the cycle
      (0.09 +/- 0.02, 0.13 +/- 0.02 and 0.09 +/- 0.01 respectively). No differences
      were found in either the protein concentration (1.8 +/- 0.3 mg/ml) or the
      quantity of proteins secreted in 24 h (1.8 +/- 0.4 mg) among oestrous cycle
      phases. In conclusion, this study provides the first characterization of buffalo
      ODF during the oestrous cycle, showing species-specific differences that may be
      useful for developing suitable media for buffalo in vitro embryo production.

PMID- 19761532
TI  - New HLA polymorphism detection by molecular and serologic typing procedures.
      Complete coding region characterization of Cw*0525, Cw*0825, B*3950 and A*3219N
      alleles.
AB  - Four new HLA class I alleles, Cw*0525, Cw*0825, B*3950 and A*3219N, have been
      characterized.

PMID- 19761533
TI  - Distribution of killer-cell immunoglobulin-like receptor genes in Eastern
      mainland Chinese Han and Taiwanese Han populations.
AB  - The interaction between killer-cell immunoglobulin-like receptors (KIRs) and
      human leukocyte antigen (HLA) molecules expressed on target cells is known to
      modulate the cytolytic activity of natural killer (NK) cells. To date, a wide
      range of KIR genotypes has been observed, which varies among different ethnic
      populations. We report here comparison of the KIR gene content and genotypic
      structure of KIRs in 106 individuals from Eastern mainland Chinese Han and 97
      from Taiwanese Han. All 17 KIR genes were observed in the two populations.
      Framework genes 2DL4, 3DL2, 3DL3 and 3DP1 were present in all individuals. The
      two populations had very similar frequencies in most loci, however, significant
      differences were noted in the frequencies of KIR3DS1 and KIR2DS4D (KIR2DS4
      deletant variant). A total of 35 and 29 genotypes were identified in the
      individuals from the Eastern mainland Chinese and the Taiwanese Hans,
      respectively. Some pairs of KIRs showed significant positive and negative linkage
      disequilibrium (LD). Our data showed that there were minor distinctions in KIR
      gene frequencies, genotypes and LD between the two populations, which shed light
      on a possible geographic genetic demarcation among different Chinese communities.

PMID- 19761535
TI  - Serum trace element levels in COPD patient: the relation between trace element
      supplementation and period of mechanical ventilation in a randomized controlled
      trial.
AB  - BACKGROUND AND OBJECTIVE: Many trace elements play important roles in activating
      or inhibiting enzymatic reactions, by competing with other elements and
      metalloproteins for binding sites, by affecting the permeability of cell
      membranes and by other mechanisms. They play important roles in the
      oxidant/antioxidant balance. As such, trace elements are thought to be involved
      directly or indirectly in the pathogenesis of several diseases. The aim of the
      present study is to investigate the effect trace elements (Se, Mn and Zn)
      intravenously administered on the period the COPD patients spend on mechanical
      ventilation. METHODS: In a randomized double-blinded controlled trial a set of
      120 subjects (40 normal volunteers and 80 COPD) were recruited. Serum
      concentration levels of Se, Mn and Zn were determined for all enrolled subjects
      with Inductively Coupled Plasma spectroscopy. COPD patients received intravenous
      supplementation of the above trace elements and the period the patients spent on
      mechanical ventilation was determined. RESULTS: There was a significant reduction
      (P = 0.013) in the period the patients with COPD spent on the mechanical
      ventilation when received intravenous supplementation (9.4 +/- 7.3 days) compared
      with the COPD patients who received placebo (17.8 +/- 7.6 days). CONCLUSIONS:
      Trace element (Se, Mn and Zn) status is altered in critically ill patients with
      COPD. The supplementation achieved a reduction in the period those patients spent
      on the mechanical ventilation. A larger multi-centre trial is required to confirm
      this preventive effect and to explore its applicability to other critical care
      conditions.

PMID- 19761534
TI  - Plasma levels of retinoids, carotenoids and tocopherols in patients with mild
      obstructive sleep apnoea.
AB  - BACKGROUND AND OBJECTIVE: OSA is associated with increased incidence of
      cardiovascular diseases. Pathogenic mechanisms of vascular diseases include
      thickened vascular walls due to the increased number of smooth muscle cells
      (SMC). Retinoic acid (RA) suppresses the growth of SMC, and reduced retinoid
      levels are associated with vascular diseases. Oxidant signalling promotes SMC
      growth, thus antioxidant levels may also influence the development of
      cardiovascular diseases. The present study tested the hypothesis that plasmas
      from OSA patients contain altered levels of retinoids, carotenoids and
      tocopherols. METHODS: Plasma samples were taken before and after sleep from
      patients with OSA (mostly mild) without known cardiovascular diseases and from
      control subjects. Levels of retinoids, carotenoids and tocopherols were measured
      using sensitive gas chromatograph-mass spectrometry and high pressure liquid
      chromatography methods and total antioxidant capacity was assessed
      fluorometrically. RESULTS: Results showed that plasmas from patients with OSA had
      significantly lower retinyl palmitate and 9-cis RA compared with control
      subjects, while levels of retinol, all-trans RA and 13-cis RA were indifferent.
      All-transbeta-carotene and 9-cisbeta-carotene were also lower in OSA patients.
      Levels of all-trans RA and 13-cis RA in OSA patients were reduced after sleep
      compared with before sleep. OSA patients showed significantly higher delta
      tocopherol compared with controls. Treatment of cultured human vascular SMC with
      post-sleep OSA patient plasmas promoted cell growth, but not in controls.
      CONCLUSIONS: Mild OSA exhibits altered levels of specific retinoids, carotenoids
      and tocopherols, which may be markers and/or mediators for the increased
      susceptibility of patients to vascular diseases.

PMID- 19761536
TI  - Cough-reflex sensitivity to inhaled capsaicin in COPD associated with increased
      exacerbation frequency.
AB  - BACKGROUND AND OBJECTIVE: The causes of exacerbations in COPD patients are poorly
      understood. This study examined the association between cough-reflex sensitivity
      in patients with stable COPD and the frequency of subsequent exacerbations.
      METHODS: The sampling frame for cases and controls for this study was patients
      attending a hospital outpatient clinic. cough-reflex sensitivity was evaluated
      using the log concentration of capsaicin causing five or more coughs (log C(5)).
      Subsequent COPD exacerbations were identified prospectively via symptom-based
      diaries over a 12-month period. RESULTS: The study group comprised 45 COPD
      subjects and 10 controls. Mean log C(5) was lower in the COPD group than in the
      control group (0.97 (95% confidence interval (CI): 0.76-1.18) versus 1.26 (95%
      CI: 0.81-1.71), P = 0.095). In the COPD group, log C(5) was negatively correlated
      with serum CRP level (r = -0.36, P = 0.02) and significantly associated with the
      exacerbation frequency (r = -0.38, P = 0.01). Stepwise multiple regression
      analysis showed that cough-reflex sensitivity was significantly associated with
      exacerbation frequency (r(2) = 0.15, P = 0.01). CONCLUSIONS: Hypersensitivity of
      the cough reflex to inhaled capsaicin might reflect airway inflammation in stable
      COPD patients, which predisposes to frequent exacerbations.

PMID- 19761537
TI  - Fractional exhaled nitric oxide in asthma: an update.
AB  - In asthma, clinical symptoms and lung function are insensitive in reflecting the
      underlying airway inflammation, and monitoring of this process has only recently
      become available. Fractional exhaled nitric oxide (Fe(NO)) is now recognized as a
      reliable surrogate marker of eosinophilic airway inflammation and offers the
      advantage of being completely non-invasive and very easy to obtain. This review
      summarizes the clinical use of Fe(NO) in asthma. It covers the relationship
      between Fe(NO) and the underlying eosinophilic inflammation, the pathophysiology
      and production of Fe(NO), technical aspects of Fe(NO) measurement and potential
      confounding factors in interpreting levels. Fe(NO) reference values and the role
      of Fe(NO) in asthma assessment, diagnosis and management are also discussed.

PMID- 19761538
TI  - Predictors of positive sputum cultures in exacerbations of chronic obstructive
      pulmonary disease.
AB  - BACKGROUND AND OBJECTIVE: Although sputum culture in patients with an acute
      exacerbation of COPD is of uncertain value, it is routinely done. The ability to
      clinically identify patients likely or unlikely to yield bacterial sputum
      isolates would potentially reduce unnecessary tests. The objective of this study
      was to identify the clinical predictors of positive sputum cultures in this
      patient population. METHODS: Consecutive patients with a COPD exacerbation
      requiring an emergency visit were prospectively enrolled. Quantitative sputum
      culture was performed on-site. Data on current smoking, sputum purulence, FEV(1),
      Medical Research Council chronic dyspnoea scale, BMI, severe exacerbations in the
      preceding year requiring hospitalization, PaO(2), PaCO(2), Acute Physiology and
      Chronic Health Evaluation (APACHE) II score, and oral and inhaled steroid use
      were recorded. RESULTS: Of the 94 patients enrolled, sputum from 36 yielded
      bacterial pathogens. These patients were characterized by a higher frequency of
      purulent sputum, lower FEV(1), BMI and PaO(2,) higher APACHE II score and more
      frequent use of inhaled steroids (P < 0.05). On multivariate regression, purulent
      sputum, FEV(1) and BMI were independent determinants of a positive sputum
      culture. Using receiver-operator-optimized thresholds for these variables
      (purulent sputum, FEV(1) < 35% predicted and BMI < or = 22 kg/m(2)), we proposed
      a regression coefficient-weighted prediction model that accurately determined the
      likelihood of sputum bacterial isolation. CONCLUSIONS: A prediction model based
      on the variables of purulent sputum, FEV(1) and BMI predicted sputum culture
      result with about 90% accuracy. Pending further validation, this model may save
      valuable healthcare resources.

PMID- 19761541
TI  - Adaptive regulation at the cell surface by N-glycosylation.
AB  - The association of receptors and solute transporters with components of the
      endocytic machinery regulates their surface levels, and thereby cellular
      sensitivity to cytokines, ligands and nutrients in the extracellular environment.
      Most transmembrane receptors and solute transporters are glycoproteins, and the
      Asn (N)-linked oligosaccharides (N-glycans) can bind animal lectins, forming
      multivalent lattices or microdomains that regulate glycoprotein mobility in the
      plane of membrane. The N-glycan number (sequence-encoded NXS/T) and context
      dependent Golgi N-glycan branching cooperate to regulate glycoprotein affinities
      for the galectin family of lectins. Galectin-3 binding reduces EGF receptor
      trafficking into clathrin-coated pits and caveolae lipid rafts, decreases ligand
      independent receptor activation and promotes alpha5beta1 integrin remodelling in
      focal adhesions. N-glycan branching in the medial Golgi increases glycan affinity
      for galectins, and the Golgi pathway is sensitive to uridine diphosphate-N
      acetylglucosamine (UDP-GlcNAc) supply, in turn hexosamine pathway metabolites
      (fructose-6-P, glutamine and acetyl-CoA). Thus, lattice avidity and cellular
      responsiveness to extracellular cues are regulated in an adaptive manner by
      metabolism and Golgi modification to glycoproteins. Computational modelling of
      the hexosamine/Golgi/lattice has provided new insight on cell surface adaptation
      in cancer and autoimmune disease.

PMID- 19761540
TI  - HCMV-encoded glycoprotein M (UL100) interacts with Rab11 effector protein FIP4.
AB  - The envelope of human cytomegalovirus (HCMV) consists of a large number of
      glycoproteins. The most abundant glycoprotein in the HCMV envelope is the
      glycoprotein M (UL100), which together with glycoprotein N (UL73) form the gM/gN
      protein complex. Using yeast two-hybrid screening, we found that the gM carboxy
      terminal cytoplasmic tail (gM-CT) interacts with FIP4, a Rab11-GTPase effector
      protein. Depletion of FIP4 expression in HCMV-infected cells resulted in a
      decrease in infectious virus production that was also associated with an
      alteration of the HCMV assembly compartment (AC) phenotype. A similar phenotype
      was also observed in HCMV-infected cells that expressed dominant negative
      Rab11(S25N). Recently, it has been shown that FIP4 interactions with Rab11 and
      additionally with Arf6/Arf5 are important for the vesicular transport of proteins
      in the endosomal recycling compartment (ERC) and during cytokinesis.
      Surprisingly, FIP4 interaction with gM-CT limited binding of FIP4 with Arf5/Arf6;
      however, FIP4 interaction with gM-CT did not prevent recruitment of Rab11 into
      the ternary complex. These data argued for a contribution of the ERC during
      cytoplasmic envelopment of HCMV and showed a novel FIP4 function independent of
      Arf5 or Arf6 activity.

PMID- 19761539
TI  - Transportin mediates nuclear entry of DNA in vertebrate systems.
AB  - Delivery of DNA to the cell nucleus is an essential step in many types of viral
      infection, transfection, gene transfer by the plant pathogen Agrobacterium
      tumefaciens and in strategies for gene therapy. Thus, the mechanism by which DNA
      crosses the nuclear pore complex (NPC) is of great interest. Using nuclei
      reconstituted in vitro in Xenopus egg extracts, we previously studied DNA passage
      through the nuclear pores using a single-molecule approach based on optical
      tweezers. Fluorescently labeled DNA molecules were also seen to accumulate within
      nuclei. Here we find that this import of DNA relies on a soluble protein receptor
      of the importin family. To identify this receptor, we used different pathway
      specific cargoes in competition studies as well as pathway-specific dominant
      negative inhibitors derived from the nucleoporin Nup153. We found that inhibition
      of the receptor transportin suppresses DNA import. In contrast, inhibition of
      importin beta has little effect on the nuclear accumulation of DNA. The
      dependence on transportin was fully confirmed in assays using permeabilized HeLa
      cells and a mammalian cell extract. We conclude that the nuclear import of DNA
      observed in these different vertebrate systems is largely mediated by the
      receptor transportin. We further report that histones, a known cargo of
      transportin, can act as an adaptor for the binding of transportin to DNA.

PMID- 19761542
TI  - Intracellular assembly and trafficking of MHC class I molecules.
AB  - The presentation of antigenic peptides by class I molecules of the major
      histocompatibility complex begins in the endoplasmic reticulum (ER) where the co
      ordinated action of molecular chaperones, folding enzymes and class I-specific
      factors ensures that class I molecules are loaded with high-affinity peptide
      ligands that will survive prolonged display at the cell surface. Once assembled,
      class I molecules are released from the quality-control machinery of the ER for
      export to the plasma membrane where they undergo dynamic endocytic cycling and
      turnover. We review recent progress in our understanding of class I assembly,
      anterograde transport and endocytosis and highlight some of the events targeted
      by viruses as a means to evade detection by cytotoxic T cells and natural killer
      cells.

PMID- 19761543
TI  - A role for the karyopherin Kap123p in microtubule stability.
AB  - Several components of the nuclear transport machinery play a role in mitotic
      spindle assembly in higher eukaryotes. To further investigate the role of this
      family of proteins in microtubule function, we screened for mutations in
      Saccharomyces cerevisiae that confer sensitivity to microtubule-destabilizing
      drugs. One mutant exhibiting this phenotype lacked the gene encoding the
      karyopherin Kap123p. Analysis of kap123Delta cells revealed that the drug
      sensitivity was caused by a defect in microtubule stability and/or assembly. In
      support of this idea, we demonstrated genetic interactions between the
      kap123Delta mutation and mutated alleles of genes encoding alpha-tubulins and
      factors controlling microtubule dynamics. Moreover, kap123Delta cells exhibit
      defects in spindle structure and dynamics as well as nuclear positioning defects
      during mitosis. Cultures of kap123Delta strains are enriched for mononucleated
      large-budded cells often containing short spindles and nuclei positioned away
      from the budneck, phenotypes indicative of defects in both cytoplasmic and
      nuclear microtubules. Finally, we identified a gene, CAJ1, which when deleted in
      combination with KAP123 exacerbated the microtubule-related defects of the
      kap123Delta mutants. We propose that Kap123p and Caj1p, a member of the Hsp40
      family of proteins, together play an essential role in normal microtubule
      function.

PMID- 19761544
TI  - Selective targeting of ER exit sites supports axon development.
AB  - During neuron development, the biosynthetic needs of the axon initially outweigh
      those of dendrites. However, although a localized role for the early secretory
      pathway in dendrite development has been observed, such a role in axon growth
      remains undefined. We therefore studied the localization of Sar1, a small GTPase
      that controls ER export, during early stages of neuronal development that are
      characterized by selective and robust axon growth. At these early stages, Sar1
      was selectively targeted to the axon where it gradually concentrated within
      varicosities in which additional proteins that function in the early secretory
      pathway were detected. Sar1 targeting to the axon followed axon specification and
      was dependent on localized actin instability. Changes in Sar1 expression levels
      at these early development stages modulated axon growth. Specifically, reduced
      expression of Sar1, which was initially only detectable in the axon, correlated
      with reduced axon growth, where as overexpression of Sar1 supported the growth of
      longer axons. In support of the former finding, expression of dominant negative
      Sar1 inhibited axon growth. Thus, as observed in lower organisms, mammalian cells
      use temporal and spatial regulation of endoplasmic reticulum exit site (ERES) to
      address developmental biosynthetic demands. Furthermore, axons, such as
      dendrites, rely on ERES targeting and assembly for growth.

PMID- 19761545
TI  - Practical guidelines for applying statistical process control to blood component
      production.
AB  - Legislation, guidelines and recommendations for blood components related to
      statistical process control (SPC) and the selection of a quality monitoring (QM)
      sampling regimen are subject to misinterpretation and lack practical guidance on
      implementation. The aim of this article is: to review and interpret applicable
      European legislation and guidelines and to develop an SPC strategy that meets
      these requirements; and to provide practical guidance on the selection and
      application of appropriate techniques and the interpretation of resultant blood
      component QM data. A methodology is presented which utilizes: an algorithm to
      select an appropriate quality-monitoring strategy for the blood component
      parameter under consideration; a range of straightforward, validated SPC
      techniques for variable data and an assessment of process capability (Cpk) and
      blood component parameter 'criticality' to determine the sampling regimen. The
      methodology was applied to routine National Health Service Blood and Transplant
      (NHSBT) blood component data for 2005-2006. Cpk values ranged from 0.22 to >3 and
      their predicted non-conformance rates were close to those observed (23 to
      <0.001%). Required sample size ranged from 0.01 to 10%. Chosen techniques
      identified significant deviation from 'as validated' performance within an
      appropriate time-scale. Thus the methodology was straightforward to apply and
      prompted the choice of a clinically and operationally appropriate sampling
      regimen and analysis for each blood component parameter. This evidence-based,
      targeted use of SPC for blood component monitoring provides an essential focus on
      processes with a low capability in achieving their specifications.

PMID- 19761546
TI  - Reviewing manuscripts: tips and responsibilities.

PMID- 19761547
TI  - Transfusion-transmitted babesiosis in Rhode Island.
AB  - BACKGROUND: Babesiosis is caused by an intraerythrocytic protozoan transmitted by
      ticks. Blood transfusion is another mode of transmission. STUDY DESIGN AND
      METHODS: This was a retrospective study based on babesiosis cases reported to the
      Rhode Island Department of Health between 1999 and 2007. Additional cases were
      also identified. RESULTS: Twenty-one cases of transfusion-transmitted babesiosis
      (TTB) were identified from 1999 through 2007. From 2005 through 2007, the
      incidence approached one case per 9000 units of blood transfused. One of 21 (5%)
      TTB cases was diagnosed in July, in sharp contrast to 65 of 152 (43%) of the
      total babesiosis cases diagnosed during July in Rhode Island. Many cases were
      identified when a complete blood count with a differential was routinely
      requested and parasites were noted by laboratory technologists. Most patients
      with TTB had underlying conditions known to predispose to symptomatic infection.
      CONCLUSION: Blood transfusion is an important mode of Babesia transmission. The
      current screening method of omitting donors with a history of babesiosis may be
      effective in preventing some, but not all, cases of TTB and current processing of
      blood products does not eradicate this parasite. Thus, a better screening test is
      needed. Alternatively, pathogen reduction technology could be utilized to prevent
      this mode of transmission.

PMID- 19761548
TI  - High-throughput red blood cell antigen genotyping using a nanofluidic real-time
      polymerase chain reaction platform.
AB  - BACKGROUND: Serologic testing of donors to obtain antigen-negative blood for
      transfusion is limited by availability and quality of reagents. Where sequence
      variant information is available, molecular typing platforms can be used to
      determine the presence of a variant allele and offer a high-throughput format
      correlated to the blood group antigen. We have investigated a flexible high
      throughput platform to screen blood donors for antigen genotypes in the African
      American population. STUDY DESIGN AND METHODS: Genomic DNA from 427 African
      American donors was analyzed for single-nucleotide polymorphisms responsible for
      red blood cell (RBC) antigens E/e, Fy(a)/Fy(b), Fy gene promoter, Jk(a)/Jk(b),
      Lu(a)/Lu(b), K/k, Js(a)/Js(b), Do(a)/Do(b), Jo(a), and Hy using primer/probe sets
      (Taqman, Applied Biosystems) on a high-throughput genotyping platform (OpenArray,
      BioTrove). Where available, the phenotype obtained by serologic testing was
      compared to genotype data. RESULTS: Serologic antigen types were available for
      2037 of the 4270 genotypes generated. There were five discordant results. Three
      resolved with repeat serologic typing, one resolved after repeat genotyping, and
      one discordance was clarified by confirmation of the BioTrove genotype by Sanger
      sequencing. Triplicate determinations were made for each sample genotype and the
      results were identical more than 99% of the time. CONCLUSIONS: The nanofluidic
      genotyping platform described here provides an accurate method for predicting
      blood group phenotypes. The user-specified array layout provides flexibility of
      target selection and number of replicate determinations and is suitable for
      screening antigen types.

PMID- 19761549
TI  - Evaluation of antimicrobial peptides as novel bactericidal agents for room
      temperature-stored platelets.
AB  - BACKGROUND: A single cost-effective pathogen inactivation approach would help to
      improve the safety of our nation's blood supply. Several methods and technologies
      are currently being studied to help reduce bacterial contamination of blood
      components. There is clearly need for simple and easy-to-use pathogen
      inactivation techniques specific to plasma, platelets (PLTs), and red blood
      cells. STUDY DESIGN AND METHODS: In this report, we introduce a novel proof of
      concept: using known therapeutic antimicrobial peptides (AMPs) as bactericidal
      agents for room temperature-stored PLT concentrates (PCs). Nine synthetic AMPs,
      four from PLT microbicidal protein-derived peptides (PD1-4) and five Arg-Trp (RW)
      repeat peptides containing one to five repeats, were tested for bactericidal
      activity in plasma and PC samples spiked with Staphylococcus aureus, S.
      epidermidis, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and
      Bacillus cereus. A 3-log reduction of viable bacteria was considered as the
      bactericidal activity of a given peptide. RESULTS: In both plasma alone and PCs,
      RW3 peptide demonstrated bactericidal activity against S. aureus, S. epidermidis,
      E. coli, P. aeruginosa, and K. pneumoniae; PD4 and RW2 against P. aeruginosa; and
      RW4 against K. pneumoniae. The activity of each of these four peptides against
      the remaining bacterial species in the test panel resulted in less than a 3-log
      reduction in the number of viable bacteria and hence considered ineffective.
      CONCLUSIONS: These findings suggest a new approach to improving the safety of
      blood components, demonstrating the potential usefulness of screening therapeutic
      AMPs against selected bacteria to identify suitable bactericidal agents for
      stored plasma, PCs, and other blood products.

PMID- 19761550
TI  - Comprehensive survey of red blood cell unit life cycle at a large teaching
      institution in eastern Canada.
AB  - BACKGROUND: Recent blood shortages and the potential clinical impact of red blood
      cell (RBC) age highlight the need to understand blood supply delivery. This study
      addresses the characteristics and mechanics of RBC unit trafficking and storage
      across the transfusion service, previously undescribed in the literature. STUDY
      DESIGN AND METHODS: This retrospective qualitative institutionwide survey
      assessed the comprehensive RBC life cycle within Capital District Health
      Authority in Nova Scotia, Canada, during 2007. RESULTS: A total of 15,930 unique
      RBC units were received from the supplier with 98.6% having mean age of 12.5
      days. The mean ages on receipt, transfusion, and time spent in the transfusion
      system before transfusion were 12, 19.6, and 7.5 days, respectively. Of 12,298
      units, 9689 (78.8%) remained within the blood transfusion services (BTSs), while
      2609 (21.2%) migrated having been returned a mean of 1.26 times from locations
      outside BTS (SD, 0.56 times), the latter spending a mean of 18.4 hours outside
      the BTS. Stationary units had mean age at dispense and time spent in the
      transfusion system of 19.2 and 6.9 days, respectively, compared to migratory
      units at 21.3 and 9.9 days, respectively (p < 0.005). A total of 5.2% (636/12258)
      of units were discarded; 423 of 636 (66.5%) were due to "unit expiry."
      CONCLUSION: Quantification of our institutional RBC life cycle highlighted key
      areas for intervention, such as the reduction of unit migration, especially D-
      units, as this increased RBC age at transfusion. In the era of limited resources,
      this method could identify areas where effort should be directed to address
      unnecessary wastage and aging of RBC units.

PMID- 19761551
TI  - Expensive blood safety initiatives may offer less benefit than we think.
AB  - BACKGROUND: Various blood safety initiatives have ensured a historically low risk
      of infection transmission through blood transfusion. Although further prevention
      of infection transmission is possible through, for example, nucleic acid testing
      and future introduction of pathogen inactivation, such initiatives are very
      costly in relation to the benefit they offer. Although estimation of the cost
      effectiveness requires detailed information about the survival of transfusion
      recipients, previous cost-effectiveness analyses have relied on incorrect
      survival assumptions. STUDY DESIGN AND METHODS: Based on empirical data of more
      than 1 million Scandinavian transfusion recipients followed for up to 20 years,
      we present two new survival functions. In a fictitious example we assessed the
      impact of survival assumptions on the estimated costs per quality-adjusted life
      year (QALY) gained, by using the survival functions of three previous cost
      effectiveness analyses along with the two new survival functions. CONCLUSIONS: We
      conclude that despite considerable costs, previous cost-effectiveness studies may
      have underestimated the costs per QALY gained by as much as 44%.

PMID- 19761552
TI  - Closure of high-volume arteriovenous fistulas improves kidney allograft function
      in patients with right heart failure.

PMID- 19761553
TI  - Impact of recurrent disease and chronic allograft nephropathy on the long-term
      allograft outcome in patients with IgA nephropathy.
AB  - SUMMARY: Although recurrent IgA nephropathy (IgAN) may lead to graft dysfunction
      after transplantation, donation from living related donor (LRD), with whom the
      risk of recurrence may be higher, is not a contraindication. Herein, we evaluated
      the natural history of allograft in recipients with IgAN and the risk factors
      influencing long-term allograft outcome. Recurrence rate and graft survival were
      assessed retrospectively in 221 IgAN patients, including transplants from 139
      LRDs (62.9%). Ten-year cumulative rate for recurrent IgAN was 30.8%. The
      operation at younger age and donation from LRD were significant for the
      recurrence by multivariate analysis. Ten-year graft survival was affected by
      recurrent IgAN (61.0% in recurrent IgAN group vs. 85.1% in nonrecurrent, P <
      0.01). However, transplants from LRDs did not show poor graft survival when
      compared with those from other types of donors. In transplants from LRDs, the
      incidence of chronic allograft nephropathy (CAN) was lower than those in grafts
      from deceased donors (10.8% vs. 19.5%, P < 0.05). When CAN was considered in
      addition to recurrence, the variance of graft survival was affected significantly
      by the development of CAN than by the recurrence. These results suggest that the
      detection and adequate management of CAN could improve graft outcome in
      transplant recipients with IgAN.

PMID- 19761554
TI  - Oesophageal metastases of hepatocellular carcinoma after liver transplantation.

PMID- 19761555
TI  - Falsely elevated whole-blood tacrolimus concentrations in a kidney-transplant
      patient: potential hazards.
AB  - SUMMARY: Tacrolimus-based immunosuppression is the most frequently prescribed
      immunosuppression for kidney-transplant (KT) patients. Because tacrolimus has a
      narrow therapeutic window, drug monitoring is mandatory. Of the many methods used
      to assess whole-blood trough levels, antibody-conjugated magnetic immunoassay
      (ACMIA) is popular because, compared with microparticle enzyme-linked
      immunoassays (MEIA), there is no need to pretreat samples, thus reducing time
      taken by the laboratory technician. Herein, we report on a KT tacrolimus-treated
      patient who experienced falsely elevated whole-blood tacrolimus concentrations
      after using the ACMIA method. ACMIA gave trough levels of 24 ng/ml, whereas the
      actual trough level, when measured by enzyme-multiplied immunoassay technique
      (EMIT) and high-performance liquid chromatography coupled with mass spectrometry
      (LC-MS/MS), was nil. After a workup we only found one factor that might have
      caused the elevated concentration: positive anti-double stranded DNA
      autoantibodies. We conclude that, when ACMIA produces surprisingly high
      tacrolimus concentrations in organ-transplant patients, these should be
      reassessed immediately using either LC-MS/MS or another immunoassay in order to
      eliminate falsely elevated results.

PMID- 19761556
TI  - Successful treatment of pulmonary hypertension secondary to congenital
      extrahepatic portocaval shunts (Abernethy type 2) by living donor liver
      transplantation after surgical shunt ligation.
AB  - In this report, we describe a living donor liver transplantation (LDLT) in a
      patient (7-year-old boy) with Abernethy type 2 congenital extrahepatic portocaval
      shunts (CEPS). This patient underwent a surgical shunt ligation as the first
      treatment for pulmonary hypertension; pulmonary hypertension was improved and
      controlled successfully 4 years after the first operation. However, pulmonary
      hypertension recurred gradually because of multiple intrahepatic portosystemic
      shunts; therefore, LDLT was performed as a radical treatment of intrahepatic
      portosystemic shunts. His pulmonary arterial pressure was also controlled 22
      months after LDLT, the postoperative continuous intravenous prostaglandin I(2)
      (PGI(2)) treatment could be withdrawn successfully. We suggest that clinicians
      carefully follow up the recurrent portosystemic shunt and cardiopulmonary
      disorders secondary to Abernethy type 2 CEPS.

PMID- 19761557
TI  - Majocchi's granuloma after antithymocyte globulin therapy in a liver transplant
      patient.
AB  - Majocchi's granuloma (MG) is an atypical and uncommon presentation of
      dermatophytic infection involving the invasion of dermal and subcutaneous tissue
      by fungal organisms. It usually begins as a suppurative folliculitis and may
      culminate in the development of widespread granulomas. Immunosuppressed patients
      are at increased risk, especially those with T-cell deficiencies. We describe a
      case of inguinal MG in a liver transplant patient who had received antithymocyte
      globulin for acute rejection.

PMID- 19761558
TI  - A multi-drug regimen for respiratory syncytial virus and parainfluenza virus
      infections in adult lung and heart-lung transplant recipients.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) and parainfluenza virus (PIV) can
      cause significant morbidity and mortality in lung and heart-lung transplant
      recipients. We evaluated the utility of a multi-drug protocol for the treatment
      of RSV- and PIV-related infections. PATIENTS AND METHODS: RSV or PIV was
      identified in 25 patients with a total of 29 infectious episodes between January
      2006 and December 2007. The study included 20 women and 5 men, mean age 42 +/- 13
      years. Fifteen patients had received bilateral lung transplant and the remainder
      either received single lung or heart-lung transplant. Mean time from transplant
      to infection was 1192 days. RSV was identified in 23 cases, PIV in 7 cases.
      Patients underwent treatment with inhaled ribavirin, methylprednisolone, and
      intravenous immunoglobulin (IVIG). RSV-positive patients were also treated with
      palivizumab. We retrospectively evaluated their clinical status and pulmonary
      function for a 1-year interval before and after the date of infection. RESULTS:
      Average baseline forced expiratory volume in 1 s (FEV(1)) before infection was
      2.14 +/- 0.68 L/min. Average decline in FEV(1) was 5.7% at the time of infection.
      Average FEV(1) during post-treatment follow-up was not significantly different
      than baseline (2.16 +/- 0.80 L/min). Among patients with bronchiolitis obliterans
      syndrome (BOS) stages 1, 2, or 3 at the time of infection, average FEV(1)
      declined by 14.8% and remained lower at 9.1% during follow-up when compared with
      patients with BOS stages 0 or 0p. No complications resulted from treatment. One
      patient died during follow-up as a result of pre-existing liver failure.
      CONCLUSIONS: This study of lung and heart-lung transplant recipients infected
      with RSV and PIV shows that a multi-drug regimen including inhaled ribavirin,
      corticosteroids, and IVIG (with or without palivizumab) is safe and effective.
      Prompt diagnosis and therapy for patients with RSV or PIV infections are critical
      for maintaining lung function.

PMID- 19761559
TI  - Disseminated adenovirus infection in renal transplant recipients: the role of
      cidofovir and intravenous immunoglobulin.
AB  - Disseminated adenovirus (ADV) infection in solid organ transplant patients is
      associated with high mortality. Limited studies have shown benefit from using
      cidofovir (CDV), as well as intravenous immunoglobulin (IVIG). In this study, we
      report 2 renal transplant patients who presented with fever and pulmonary
      infiltrates. Both patients continued to worsen despite antibiotic therapy.
      Bronchoalveolar lavage viral culture and serum polymerase chain reaction (PCR)
      were positive for ADV. Patients were treated with CDV, IVIG, and reduction in
      immunosuppression. A progressive decline in serum ADV DNA by PCR correlated with
      clinical improvement and pulmonary infiltrates improved. Both patients recovered.
      Allograft function was preserved although reversible acute kidney injury was
      observed in both patients. To the best of our knowledge, this is the first
      successful use of CDV and IVIG in renal transplant patients with disseminated ADV
      infection.

PMID- 19761560
TI  - What is your diagnosis? Blood film from an icteric cat.

PMID- 19761561
TI  - Serum alpha-1-acid glycoprotein concentration in clinically healthy puppies and
      adult dogs and in dogs with various diseases.
AB  - BACKGROUND: alpha-1-acid glycoprotein (AGP) is an acute-phase protein and a serum
      marker of inflammation and neoplasia in humans. AGP concentrations in diseased
      dogs and the potential effects of age, breed, and sex have not been elucidated.
      OBJECTIVE: The purpose of this study was to examine differences in AGP
      concentration based on age, sex, and breed in a large population of clinically
      healthy dogs and to compare AGP concentrations in dogs with various diseases.
      METHODS: Serum was obtained from clinically healthy puppies (n=74) and adults
      (n=172) of both sexes, and included mongrels (n=205) and Beagles (n=41). Serum
      also was obtained from 192 dogs with various diseases, including 8 with pyometra
      that were sampled before, and 1, 2, 3, and 10 days after surgery. AGP
      concentration was measured by single radial immunodiffusion. Statistical
      comparisons were made among age, sex, breed, and disease groups. RESULTS: Serum
      AGP in healthy adult mongrels was 364+/-106 mg/L (reference interval, 152-576
      mg/L). AGP was lowest in newborns (n=11, 122+/-54 mg/L) and gradually increased
      to adult levels by 3 months of age. Median AGP concentration was highest in dogs
      with parvovirus (n=17, 2100 mg/L), distemper (n=7, 1250 mg/L), and pyometra
      (n=18, 2480 mg/L) and was also significantly higher in dogs with acute
      filariasis, renal failure, urolithiasis, pancreatitis, hepatitis, trauma,
      hyperadrenocorticism, and immune-mediated hemolytic anemia. Dogs with acute
      filariasis and acute hepatopathy had significantly higher AGP concentrations than
      dogs with chronic filariasis and chronic hepatopathy. Serum AGP concentration
      decreased gradually following surgery for pyometra but remained increased after
      10 days (896+/-175 mg/L). CONCLUSIONS: Because of significantly lower AGP in
      puppies, the age of dogs should be considered when using AGP as a marker of
      disease. Serum AGP may be a useful marker of inflammatory disease in dogs and may
      help differentiate acute and chronic stages of disease.

PMID- 19761562
TI  - Selected proceedings of the 2009 Summit on Translational Bioinformatics.

PMID- 19761563
TI  - Transcriptional network classifiers.
AB  - BACKGROUND: Gene interactions play a central role in transcriptional networks.
      Many studies have performed genome-wide expression analysis to reconstruct
      regulatory networks to investigate disease processes. Since biological processes
      are outcomes of regulatory gene interactions, this paper develops a system
      biology approach to infer function-dependent transcriptional networks modulating
      phenotypic traits, which serve as a classifier to identify tissue states. Due to
      gene interactions taken into account in the analysis, we can achieve higher
      classification accuracy than existing methods. RESULTS: Our system biology
      approach is carried out by the Bayesian networks framework. The algorithm
      consists of two steps: gene filtering by Bayes factor followed by collinearity
      elimination via network learning. We validate our approach with two clinical
      data. In the study of lung cancer subtypes discrimination, we obtain a 25-gene
      classifier from 111 training samples, and the test on 422 independent samples
      achieves 95% classification accuracy. In the study of thoracic aortic aneurysm
      (TAA) diagnosis, 61 samples determine a 34-gene classifier, whose diagnosis
      accuracy on 33 independent samples achieves 82%. The performance comparisons with
      three other popular methods, PCA/LDA, PAM, and Weighted Voting, confirm that our
      approach yields superior classification accuracy and a more compact signature.
      CONCLUSIONS: The system biology approach presented in this paper is able to infer
      function-dependent transcriptional networks, which in turn can classify
      biological samples with high accuracy. The validation of our classifier using
      clinical data demonstrates the promising value of our proposed approach for
      disease diagnosis.

PMID- 19761564
TI  - Evaluation of a large-scale biomedical data annotation initiative.
AB  - BACKGROUND: This study describes a large-scale manual re-annotation of data
      samples in the Gene Expression Omnibus (GEO), using variables and values derived
      from the National Cancer Institute thesaurus. A framework is described for
      creating an annotation scheme for various diseases that is flexible,
      comprehensive, and scalable. The annotation structure is evaluated by measuring
      coverage and agreement between annotators. RESULTS: There were 12,500 samples
      annotated with approximately 30 variables, in each of six disease categories -
      breast cancer, colon cancer, inflammatory bowel disease (IBD), rheumatoid
      arthritis (RA), systemic lupus erythematosus (SLE), and Type 1 diabetes mellitus
      (DM). The annotators provided excellent variable coverage, with known values for
      over 98% of three critical variables: disease state, tissue, and sample type.
      There was 89% strict inter-annotator agreement and 92% agreement when using
      semantic and partial similarity measures. CONCLUSION: We show that it is possible
      to perform manual re-annotation of a large repository in a reliable manner.

PMID- 19761565
TI  - Evaluating the accuracy of a functional SNP annotation system.
AB  - Many common and chronic diseases are influenced at some level by genetic
      variation. Research done in population genetics, specifically in the area of
      single nucleotide polymorphisms (SNPs) is critical to understanding human genetic
      variation. A key element in assessing role of a given SNP is determining if the
      variation is likely to result in change in function. The SNP Integration Tool
      (SNPit) is a comprehensive tool that integrates diverse, existing predictors of
      SNP functionality, providing the user with information for improved association
      study analysis. To evaluate the SNPit system, we developed an alternative gold
      standard to measure accuracy using sensitivity and specificity. The results of
      our evaluation demonstrated that our alternative gold standard produced
      encouraging results.

PMID- 19761566
TI  - Developing a manually annotated clinical document corpus to identify phenotypic
      information for inflammatory bowel disease.
AB  - BACKGROUND: Natural Language Processing (NLP) systems can be used for specific
      Information Extraction (IE) tasks such as extracting phenotypic data from the
      electronic medical record (EMR). These data are useful for translational research
      and are often found only in free text clinical notes. A key required step for IE
      is the manual annotation of clinical corpora and the creation of a reference
      standard for (1) training and validation tasks and (2) to focus and clarify NLP
      system requirements. These tasks are time consuming, expensive, and require
      considerable effort on the part of human reviewers. METHODS: Using a set of
      clinical documents from the VA EMR for a particular use case of interest we
      identify specific challenges and present several opportunities for annotation
      tasks. We demonstrate specific methods using an open source annotation tool, a
      customized annotation schema, and a corpus of clinical documents for patients
      known to have a diagnosis of Inflammatory Bowel Disease (IBD). We report
      clinician annotator agreement at the document, concept, and concept attribute
      level. We estimate concept yield in terms of annotated concepts within specific
      note sections and document types. RESULTS: Annotator agreement at the document
      level for documents that contained concepts of interest for IBD using estimated
      Kappa statistic (95% CI) was very high at 0.87 (0.82, 0.93). At the concept
      level, F-measure ranged from 0.61 to 0.83. However, agreement varied greatly at
      the specific concept attribute level. For this particular use case (IBD),
      clinical documents producing the highest concept yield per document included GI
      clinic notes and primary care notes. Within the various types of notes, the
      highest concept yield was in sections representing patient assessment and history
      of presenting illness. Ancillary service documents and family history and plan
      note sections produced the lowest concept yield. CONCLUSION: Challenges include
      defining and building appropriate annotation schemas, adequately training
      clinician annotators, and determining the appropriate level of information to be
      annotated. Opportunities include narrowing the focus of information extraction to
      use case specific note types and sections, especially in cases where NLP systems
      will be used to extract information from large repositories of electronic
      clinical note documents.

PMID- 19761567
TI  - Characterizing environmental and phenotypic associations using information theory
      and electronic health records.
AB  - BACKGROUND: The availability of up-to-date, executable, evidence-based medical
      knowledge is essential for many clinical applications, such as pharmacovigilance,
      but executable knowledge is costly to obtain and update. Automated acquisition of
      environmental and phenotypic associations in biomedical and clinical documents
      using text mining has showed some success. The usefulness of the association
      knowledge is limited, however, due to the fact that the specific relationships
      between clinical entities remain unknown. In particular, some associations are
      indirect relations due to interdependencies among the data. RESULTS: In this
      work, we develop methods using mutual information (MI) and its property, the data
      processing inequality (DPI), to help characterize associations that were
      generated based on use of natural language processing to encode clinical
      information in narrative patient records followed by statistical methods.
      Evaluation based on a random sample consisting of two drugs and two diseases
      indicates an overall precision of 81%. CONCLUSION: This preliminary study
      demonstrates that the proposed method is effective for helping to characterize
      phenotypic and environmental associations obtained from clinical reports.

PMID- 19761568
TI  - Comparison of concept recognizers for building the Open Biomedical Annotator.
AB  - The National Center for Biomedical Ontology (NCBO) is developing a system for
      automated, ontology-based access to online biomedical resources (Shah NH, et al.:
      Ontology-driven indexing of public datasets for translational bioinformatics. BMC
      Bioinformatics 2009, 10(Suppl 2):S1). The system's indexing workflow processes
      the text metadata of diverse resources such as datasets from GEO and ArrayExpress
      to annotate and index them with concepts from appropriate ontologies. This
      indexing requires the use of a concept-recognition tool to identify ontology
      concepts in the resource's textual metadata. In this paper, we present a
      comparison of two concept recognizers - NLM's MetaMap and the University of
      Michigan's Mgrep. We utilize a number of data sources and dictionaries to
      evaluate the concept recognizers in terms of precision, recall, speed of
      execution, scalability and customizability. Our evaluations demonstrate that
      Mgrep has a clear edge over MetaMap for large-scale service oriented
      applications. Based on our analysis we also suggest areas of potential
      improvements for Mgrep. We have subsequently used Mgrep to build the Open
      Biomedical Annotator service. The Annotator service has access to a large
      dictionary of biomedical terms derived from the United Medical Language System
      (UMLS) and NCBO ontologies. The Annotator also leverages the hierarchical
      structure of the ontologies and their mappings to expand annotations. The
      Annotator service is available to the community as a REST Web service for
      creating ontology-based annotations of their data.

PMID- 19761569
TI  - Feature selection for fMRI-based deception detection.
AB  - BACKGROUND: Functional magnetic resonance imaging (fMRI) is a technology used to
      detect brain activity. Patterns of brain activation have been utilized as
      biomarkers for various neuropsychiatric applications. Detecting deception based
      on the pattern of brain activation characterized with fMRI is getting attention -
      with machine learning algorithms being applied to this field in recent years. The
      high dimensionality of fMRI data makes it a difficult task to directly utilize
      the original data as input for classification algorithms in detecting deception.
      In this paper, we investigated the procedures of feature selection to enhance
      fMRI-based deception detection. RESULTS: We used the t-statistic map derived from
      the statistical parametric mapping analysis of fMRI signals to construct features
      that reflect brain activation patterns. We subsequently investigated various
      feature selection methods including an ensemble method to identify discriminative
      features to detect deception. Using 124 features selected from a set of 65,166
      original features as inputs for a support vector machine classifier, our results
      indicate that feature selection significantly enhanced the classification
      accuracy of the support vector machine in comparison to the models trained using
      all features and dimension reduction based models. Furthermore, the selected
      features are shown to form anatomic clusters within brain regions, which supports
      the hypothesis that specific brain regions may play a role during deception
      processes. CONCLUSION: Feature selection not only enhances classification
      accuracy in fMRI-based deception detection but also provides support for the
      biological hypothesis that brain activities in certain regions of the brain are
      important for discrimination of deception.

PMID- 19761570
TI  - Knowledge-based variable selection for learning rules from proteomic data.
AB  - BACKGROUND: The incorporation of biological knowledge can enhance the analysis of
      biomedical data. We present a novel method that uses a proteomic knowledge base
      to enhance the performance of a rule-learning algorithm in identifying putative
      biomarkers of disease from high-dimensional proteomic mass spectral data. In
      particular, we use the Empirical Proteomics Ontology Knowledge Base (EPO-KB) that
      contains previously identified and validated proteomic biomarkers to select m/zs
      in a proteomic dataset prior to analysis to increase performance. RESULTS: We
      show that using EPO-KB as a pre-processing method, specifically selecting all
      biomarkers found only in the biofluid of the proteomic dataset, reduces the
      dimensionality by 95% and provides a statistically significantly greater increase
      in performance over no variable selection and random variable selection.
      CONCLUSION: Knowledge-based variable selection even with a sparsely-populated
      resource such as the EPO-KB increases overall performance of rule-learning for
      disease classification from high-dimensional proteomic mass spectra.

PMID- 19761571
TI  - Structural similarity assessment for drug sensitivity prediction in cancer.
AB  - BACKGROUND: The ability to predict drug sensitivity in cancer is one of the
      exciting promises of pharmacogenomic research. Several groups have demonstrated
      the ability to predict drug sensitivity by integrating chemo-sensitivity data and
      associated gene expression measurements from large anti-cancer drug screens such
      as NCI-60. The general approach is based on comparing gene expression
      measurements from sensitive and resistant cancer cell lines and deriving drug
      sensitivity profiles consisting of lists of genes whose expression is predictive
      of response to a drug. Importantly, it has been shown that such profiles are
      generic and can be applied to cancer cell lines that are not part of the anti
      cancer screen. However, one limitation is that the profiles can not be generated
      for untested drugs (i.e., drugs that are not part of an anti-cancer drug screen).
      In this work, we propose using an existing drug sensitivity profile for drug A as
      a substitute for an untested drug B given high structural similarities between
      drugs A and B. RESULTS: We first show that structural similarity between pairs of
      compounds in the NCI-60 dataset highly correlates with the similarity between
      their activities across the cancer cell lines. This result shows that
      structurally similar drugs can be expected to have a similar effect on cancer
      cell lines. We next set out to test our hypothesis that we can use existing drug
      sensitivity profiles as substitute profiles for untested drugs. In a cross
      validation experiment, we found that the use of substitute profiles is possible
      without a significant loss of prediction accuracy if the substitute profile was
      generated from a compound with high structural similarity to the untested
      compound. CONCLUSION: Anti-cancer drug screens are a valuable resource for
      generating omics-based drug sensitivity profiles. We show that it is possible to
      extend the usefulness of existing screens to untested drugs by deriving
      substitute sensitivity profiles from structurally similar drugs part of the
      screen.

PMID- 19761572
TI  - Analysis of AML genes in dysregulated molecular networks.
AB  - BACKGROUND: Identifying disease causing genes and understanding their molecular
      mechanisms are essential to developing effective therapeutics. Thus, several
      computational methods have been proposed to prioritize candidate disease genes by
      integrating different data types, including sequence information, biomedical
      literature, and pathway information. Recently, molecular interaction networks
      have been incorporated to predict disease genes, but most of those methods do not
      utilize invaluable disease-specific information available in mRNA expression
      profiles of patient samples. RESULTS: Through the integration of protein-protein
      interaction networks and gene expression profiles of acute myeloid leukemia (AML)
      patients, we identified subnetworks of interacting proteins dysregulated in AML
      and characterized known mutation genes causally implicated to AML embedded in the
      subnetworks. The analysis shows that the set of extracted subnetworks is a
      reservoir rich in AML genes reflecting key leukemogenic processes such as myeloid
      differentiation. CONCLUSION: We showed that the integrative approach both
      utilizing gene expression profiles and molecular networks could identify AML
      causing genes most of which were not detectable with gene expression analysis
      alone due to the minor changes in mRNA level.

PMID- 19761573
TI  - Network analysis of genes regulated in renal diseases: implications for a
      molecular-based classification.
AB  - BACKGROUND: Chronic renal diseases are currently classified based on
      morphological similarities such as whether they produce predominantly
      inflammatory or non-inflammatory responses. However, such classifications do not
      reliably predict the course of the disease and its response to therapy. In
      contrast, recent studies in diseases such as breast cancer suggest that a
      classification which includes molecular information could lead to more accurate
      diagnoses and prediction of treatment response. This article describes how we
      extracted gene expression profiles from biopsies of patients with chronic renal
      diseases, and used network visualizations and associated quantitative measures to
      rapidly analyze similarities and differences between the diseases. RESULTS: The
      analysis revealed three main regularities: (1) Many genes associated with a
      single disease, and fewer genes associated with many diseases. (2) Unexpected
      combinations of renal diseases that share relatively large numbers of genes. (3)
      Uniform concordance in the regulation of all genes in the network. CONCLUSION:
      The overall results suggest the need to define a molecular-based classification
      of renal diseases, in addition to hypotheses for the unexpected patterns of
      shared genes and the uniformity in gene concordance. Furthermore, the results
      demonstrate the utility of network analyses to rapidly understand complex
      relationships between diseases and regulated genes.

PMID- 19761574
TI  - Infection in the intensive care unit alters physiological networks.
AB  - BACKGROUND: Physicians use clinical and physiological data to treat patients
      every day, and it is essential for treating a patient appropriately. However,
      medical sources of clinical physiological data are only now starting to find use
      in bioinformatics research. RESULTS: We collected 29 types of physiological and
      clinical data on a minute-by-minute basis from trauma patients in the intensive
      care unit along with whether they contracted an infection during their stay.
      Dividing the patients into two groups based on this criterion, we determined that
      the correlational network amongst pairs of physiological variables changes based
      on whether the patient contracted an infection. CONCLUSION: Examining the
      variable pairs with the largest change in correlation across groups reveals
      potential changes in the way our treatments affect the patient's physiology and
      in how our bodies react to physiological insults. These findings highlight the
      usefulness of physiological informatics and suggest new relationships to study
      while also validating previously reported relationships.

PMID- 19761575
TI  - A systems biology approach to the identification and analysis of transcriptional
      regulatory networks in osteocytes.
AB  - BACKGROUND: The osteocyte is a type of cell that appears to be one of the key
      endocrine regulators of bone metabolism and a key responder to initiate bone
      formation and remodeling. Identifying the regulatory networks in osteocytes may
      lead to new therapies for osteoporosis and loss of bone. RESULTS: Using
      microarray, we identified 269 genes over-expressed in osteocyte, many of which
      have known functions in bone and muscle differentiation and contractility. We
      determined the evolutionarily conserved and enriched TF binding sites in the 5 kb
      promoter regions of these genes. Using this data, a transcriptional regulatory
      network was constructed and subsequently partitioned to identify cis-regulatory
      modules. CONCLUSION: Our results show that many osteocyte-specific genes,
      including two well-known osteocyte markers DMP1 and Sost, have highly conserved
      clustering of muscle-related cis-regulatory modules, thus supporting the concept
      that a muscle-related gene network is important in osteocyte biology and may play
      a role in contractility and dynamic movements of the osteocyte.

PMID- 19761577
TI  - PAPAyA: a platform for breast cancer biomarker signature discovery, evaluation
      and assessment.
AB  - BACKGROUND: The decision environment for cancer care is becoming increasingly
      complex due to the discovery and development of novel genomic tests that offer
      information regarding therapy response, prognosis and monitoring, in addition to
      traditional histopathology. There is, therefore, a need for translational
      clinical tools based on molecular bioinformatics, particularly in current cancer
      care, that can acquire, analyze the data, and interpret and present information
      from multiple diagnostic modalities to help the clinician make effective
      decisions. RESULTS: We present a platform for molecular signature discovery and
      clinical decision support that relies on genomic and epigenomic measurement
      modalities as well as clinical parameters such as histopathological results and
      survival information. Our Physician Accessible Preclinical Analytics Application
      (PAPAyA) integrates a powerful set of statistical and machine learning tools that
      leverage the connections among the different modalities. It is easily extendable
      and reconfigurable to support integration of existing research methods and tools
      into powerful data analysis and interpretation pipelines. A current configuration
      of PAPAyA with examples of its performance on breast cancer molecular profiles is
      used to present the platform in action. CONCLUSION: PAPAyA enables analysis of
      data from (pre)clinical studies, formulation of new clinical hypotheses, and
      facilitates clinical decision support by abstracting molecular profiles for
      clinicians.

PMID- 19761576
TI  - Mechanism-anchored profiling derived from epigenetic networks predicts outcome in
      acute lymphoblastic leukemia.
AB  - BACKGROUND: Current outcome predictors based on "molecular profiling" rely on
      gene lists selected without consideration for their molecular mechanisms. This
      study was designed to demonstrate that we could learn about genes related to a
      specific mechanism and further use this knowledge to predict outcome in patients 
      a paradigm shift towards accurate "mechanism-anchored profiling". We propose a
      novel algorithm, PGnet, which predicts a tripartite mechanism-anchored network
      associated to epigenetic regulation consisting of phenotypes, genes and
      mechanisms. Genes termed as GEMs in this network meet all of the following
      criteria: (i) they are co-expressed with genes known to be involved in the
      biological mechanism of interest, (ii) they are also differentially expressed
      between distinct phenotypes relevant to the study, and (iii) as a biomodule,
      genes correlate with both the mechanism and the phenotype. RESULTS: This proof-of
      concept study, which focuses on epigenetic mechanisms, was conducted in a well
      studied set of 132 acute lymphoblastic leukemia (ALL) microarrays annotated with
      nine distinct phenotypes and three measures of response to therapy. We used
      established parametric and non parametric statistics to derive the PGnet
      tripartite network that consisted of 10 phenotypes and 33 significant clusters of
      GEMs comprising 535 distinct genes. The significance of PGnet was estimated from
      empirical p-values, and a robust subnetwork derived from ALL outcome data was
      produced by repeated random sampling. The evaluation of derived robust network to
      predict outcome (relapse of ALL) was significant (p = 3%), using one hundred
      three-fold cross-validations and the shrunken centroids classifier. CONCLUSION:
      To our knowledge, this is the first method predicting co-expression networks of
      genes associated with epigenetic mechanisms and to demonstrate its inherent
      capability to predict therapeutic outcome. This PGnet approach can be applied to
      any regulatory mechanisms including transcriptional or microRNA regulation in
      order to derive predictive molecular profiles that are mechanistically anchored.
      The implementation of PGnet in R is freely available at
      http://Lussierlab.org/publication/PGnet.

PMID- 19761578
TI  - The potential for automated question answering in the context of genomic
      medicine: an assessment of existing resources and properties of answers.
AB  - Knowledge gained in studies of genetic disorders is reported in a growing body of
      biomedical literature containing reports of genetic variation in individuals that
      map to medical conditions and/or response to therapy. These scientific
      discoveries need to be translated into practical applications to optimize patient
      care. Translating research into practice can be facilitated by supplying
      clinicians with research evidence. We assessed the role of existing tools in
      extracting answers to translational research questions in the area of genomic
      medicine. We: evaluate the coverage of translational research terms in the
      Unified Medical Language Systems (UMLS) Metathesaurus; determine where answers
      are most often found in full-text articles; and determine common answer patterns.
      Findings suggest that we will be able to leverage the UMLS in development of
      natural language processing algorithms for automated extraction of answers to
      translational research questions from biomedical text in the area of genomic
      medicine.

PMID- 19761579
TI  - Towards large-scale sample annotation in gene expression repositories.
AB  - BACKGROUND: Large repositories of biomedical research data are most useful to
      translational researchers if their data can be aggregated for efficient queries
      and analyses. However, inconsistent or non-existent annotations describing
      important sample details such as name of tissue or cell line, histopathological
      type, and subject characteristics like demographics, treatment, and survival are
      seldom present in data repositories, making it difficult to aggregate data.
      RESULTS: We created a flexible software tool that allows efficient annotation of
      samples using a controlled vocabulary, and report on its use for the annotation
      of over 12,500 samples. CONCLUSION: While the amount of data is very large and
      seemingly poorly annotated, a lot of information is still within reach.
      Consistent tool-based re-annotation enables many new possibilities for large
      scale interpretation and analyses that would otherwise be impossible.

PMID- 19761580
TI  - Dutch healthcare reform: did it result in performance improvement of health
      plans? A comparison of consumer experiences over time.
AB  - BACKGROUND: Many countries have introduced elements of managed competition in
      their healthcare system with the aim to accomplish more efficient and demand
      driven health care. Simultaneously, generating and reporting of comparative
      healthcare information has become an important quality-improvement instrument. We
      examined whether the introduction of managed competition in the Dutch healthcare
      system along with public reporting of quality information was associated with
      performance improvement in health plans. METHODS: Experiences of consumers with
      their health plan were measured in four consecutive years (2005-2008) using the
      CQI(R) health plan instrument 'Experiences with Healthcare and Health Insurer'.
      Data were available of 13,819 respondents (response = 45%) of 30 health plans in
      2005, of 8,266 respondents (response = 39%) of 32 health plans in 2006, of 8,088
      respondents (response = 34%) of 32 health plans in 2007, and of 7,183 respondents
      (response = 31%) of 32 health plans in 2008. We performed multilevel regression
      analyses with three levels: respondent, health plan and year of measurement. Per
      year and per quality aspect, we estimated health plan means while adjusting for
      consumers' age, education and self-reported health status. We tested for linear
      and quadratic time effects using chi-squares. RESULTS: The overall performance of
      health plans increased significantly from 2005 to 2008 on four quality aspects.
      For three other aspects, we found that the overall performance first declined and
      then increased from 2006 to 2008, but the performance in 2008 was not better than
      in 2005. The overall performance of health plans did not improve more often for
      quality aspects that were identified as important areas of improvement in the
      first year of measurement. On six out of seven aspects, the performance of health
      plans that scored below average in 2005 increased more than the performance of
      health plans that scored average and/or above average in that year. CONCLUSION:
      We found mixed results concerning the effects of managed competition on the
      performance of health plans. To determine whether managed competition in the
      healthcare system leads to quality improvement in health plans, it is important
      to examine whether and for what reasons health plans initiate improvement
      efforts.

PMID- 19761581
TI  - Cardiac injuries in blunt chest trauma.
AB  - Blunt chest traumas are a clinical challenge, both for diagnosis and treatment.
      The use of cardiovascular magnetic resonance can play a major role in this
      setting. We present two cases: a 12-year-old boy and 45-year-old man. Late
      gadolinium enhancement imaging enabled visualization of myocardial damage
      resulting from the trauma.

PMID- 19761582
TI  - Anti-proliferative activity of silver nanoparticles.
AB  - BACKGROUND: Nanoparticles possess exceptional physical and chemical properties
      which led to rapid commercialisation. Silver nanoparticles (Ag-np) are among the
      most commercialized nanoparticles due to their antimicrobial potential. Ag-np
      based cosmetics, therapeutic agents and household products are in wide use, which
      raised a public concern regarding their safety associated with human and
      environmental use. No safety regulations are in practice for the use of these
      nanomaterials. The interactions of nanomaterials with cells, uptake mechanisms,
      distribution, excretion, toxicological endpoints and mechanism of action remain
      unanswered. RESULTS: Normal human lung fibroblasts (IMR-90) and human
      glioblastoma cells (U251) were exposed to different doses of Ag-nps in vitro.
      Uptake of Ag-nps occurred mainly through endocytosis (clathrin mediated process
      and macropinocytosis), accompanied by a time dependent increase in exocytosis
      rate. The electron micrographs revealed a uniform intracellular distribution of
      Ag-np both in cytoplasm and nucleus. Ag-np treated cells exhibited chromosome
      instability and mitotic arrest in human cells. There was efficient recovery from
      arrest in normal human fibroblasts whereas the cancer cells ceased to
      proliferate. Toxicity of Ag-np is mediated through intracellular calcium (Ca2+)
      transients along with significant alterations in cell morphology and spreading
      and surface ruffling. Down regulation of major actin binding protein, filamin was
      observed after Ag-np exposure. Ag-np induced stress resulted in the up regulation
      of metallothionein and heme oxygenase -1 genes. CONCLUSION: Here, we demonstrate
      that uptake of Ag-np occurs mainly through clathrin mediated endocytosis and
      macropinocytosis. Our results suggest that cancer cells are susceptible to damage
      with lack of recovery from Ag-np-induced stress. Ag-np is found to be acting
      through intracellular calcium transients and chromosomal aberrations, either
      directly or through activation of catabolic enzymes. The signalling cascades are
      believed to play key roles in cytoskeleton deformations and ultimately to inhibit
      cell proliferation.

PMID- 19761583
TI  - Sexual dysfunction following surgery for rectal cancer - a clinical and
      neurophysiological study.
AB  - BACKGROUND: Sexual dysfunction following surgery for rectal cancer may be
      frequent and often severe. The aim of the present study is to evaluate the
      occurrence of this complication from both a clinical point of view and by means
      of neurophysiological tests. METHODS: We studied a group of 57 patients submitted
      to rectal resection for adenocarcinoma. All the patients underwent neurological,
      psychological and the following neurophysiological tests: sacral reflex (SR),
      pudendal somatosensory evoked potentials (PEPs), motor evoked potential (MEPs)
      and sympathetic skin responses (SSRs). The results were compared with a control
      group of 67 rectal cancer patients studied before surgery. Only 10 of these
      patients could be studied both pre- and postoperatively. 10 patients submitted to
      high dose preoperative chemoradiation were studied to evaluate the effect of this
      treatment on sexual function. Statistical analysis was performed by means of the
      two-tailed Student's t test for paired observations and k concordance test.
      RESULTS: 59.6% of patients operated reported sexual dysfunction, while this
      symptom occurred in 16.4% in the control group. Moreover, a significantly higher
      rate of alterations of the neurophysiological tests and longer mean latencies of
      the SR, PEPs, MEPs and SSRs were observed in the patients who had undergone
      resection. In the 10 patients studied both pre and post-surgery impotence
      occurred in 6 of them and the mean latencies of SSRs were longer after operation.
      In the 10 patients studied pre and post chemoradiation impotence occurred in 1
      patient only, showing the mild effect of these treatments on sexual function.
      CONCLUSION: Patients operated showed severe sexual dysfunctions. The
      neurophysiological test may be a useful tool to investigate this complication.
      The neurological damage could be monitored to decide the rehabilitation strategy.

PMID- 19761584
TI  - Developmental psychopathology: Attention Deficit Hyperactivity Disorder (ADHD).
AB  - BACKGROUND: Attention Deficit/Hyperactivity Disorder (ADHD), formerly regarded as
      a typical childhood disorder, is now known as a developmental disorder persisting
      over the lifespan. Starting in preschool-age, symptoms vary depending on the age
      group affected. METHOD: According to the variability of ADHD-symptoms and the
      heterogeneity of comorbid psychiatric disorders, a broad review of recent studies
      was performed. These findings were summarized in a developmental
      psychopathological model, documenting relevant facts on a timeline. RESULTS:
      Based on a genetic disposition and a neuropsychological deregulation, there is
      evidence for factors which persist across the lifespan, change age-dependently,
      or show validity in a specific developmental phase. Qualitative changes can be
      found for children in preschool-age and adults. CONCLUSION: These differences
      have implications for clinical practice as they can be used for prevention,
      diagnostic proceedings, and therapeutic intervention as well as for planning
      future studies. The present article is a translated and modified version of the
      German article "Entwicklungspsychopathologie der ADHS", published in Zeitschrift
      fur Psychiatrie, Psychologie und Psychotherapie, 56, 2008, S. 265-274.

PMID- 19761585
TI  - Identification of a novel motif responsible for the distinctive transforming
      activity of human T-cell leukemia virus (HTLV) type 1 Tax1 protein from HTLV-2
      Tax2.
AB  - BACKGROUND: Human T-cell leukemia virus type 1 (HTLV-1) is a causative agent of
      adult T-cell leukemia (ATL), whereas its relative HTLV-2 is not associated with
      any malignancies including ATL. HTLV-1 Tax1 transformed a T-cell line from
      interleukin (IL)-2-dependent growth to IL-2-independent growth, with an activity
      that was much more potent in comparison to HTLV-2 Tax2. This distinction was
      mediated by at least two Tax1 specific functions, an interaction with host
      cellular factors through the PDZ domain binding motif (PBM) and the activation of
      NF-kappa B2 (NF-kappa B2)/p100. RESULTS: Using a series of Tax1 chimeric proteins
      with Tax2, we found that amino acids 225-232 of Tax1, the Tax1(225-232) region,
      was essential for the activation of NF-kappa B2 as well as for the high
      transforming activity. The strict amino acid conservation of Tax1(225-232) among
      HTLV-1 and simian T-cell leukemia virus type 1 (STLV-1), but not HTLV-2 and STLV
      2, indicates that function(s) through the Tax1(225-232) region are biologically
      significant. Interestingly, another HTLV-1 relative, HTLV-3, has a PBM, but does
      not conserve the Tax1(225-232) motif in Tax3, thus indicating that these two
      motifs classify the three HTLVs into the separate groups. CONCLUSION: These
      results suggest that the combinatory functions through Tax1(225-232) and PBM play
      crucial roles in the distinct biological properties of the three HTLVs, perhaps
      also including their pathogenesis.

PMID- 19761586
TI  - Assessment of three Resistance-Nodulation-Cell Division drug efflux transporters
      of Burkholderia cenocepacia in intrinsic antibiotic resistance.
AB  - BACKGROUND: Burkholderia cenocepacia are opportunistic Gram-negative bacteria
      that can cause chronic pulmonary infections in patients with cystic fibrosis.
      These bacteria demonstrate a high-level of intrinsic antibiotic resistance to
      most clinically useful antibiotics complicating treatment. We previously
      identified 14 genes encoding putative Resistance-Nodulation-Cell Division (RND)
      efflux pumps in the genome of B. cenocepacia J2315, but the contribution of these
      pumps to the intrinsic drug resistance of this bacterium remains unclear.
      RESULTS: To investigate the contribution of efflux pumps to intrinsic drug
      resistance of B. cenocepacia J2315, we deleted 3 operons encoding the putative
      RND transporters RND-1, RND-3, and RND-4 containing the genes BCAS0591-BCAS0593,
      BCAL1674-BCAL1676, and BCAL2822-BCAL2820. Each deletion included the genes
      encoding the RND transporter itself and those encoding predicted periplasmic
      proteins and outer membrane pores. In addition, the deletion of rnd-3 also
      included BCAL1672, encoding a putative TetR regulator. The B. cenocepacia rnd-3
      and rnd-4 mutants demonstrated increased sensitivity to inhibitory compounds,
      suggesting an involvement of these proteins in drug resistance. Moreover, the rnd
      3 and rnd-4 mutants demonstrated reduced accumulation of N-acyl homoserine
      lactones in the growth medium. In contrast, deletion of the rnd-1 operon had no
      detectable phenotypes under the conditions assayed. CONCLUSION: Two of the three
      inactivated RND efflux pumps in B. cenocepacia J2315 contribute to the high level
      of intrinsic resistance of this strain to some antibiotics and other inhibitory
      compounds. Furthermore, these efflux systems also mediate accumulation in the
      growth medium of quorum sensing molecules that have been shown to contribute to
      infection. A systematic study of RND efflux systems in B. cenocepacia is required
      to provide a full picture of intrinsic antibiotic resistance in this
      opportunistic bacterium.

PMID- 19761587
TI  - Mapping of HNF4alpha target genes in intestinal epithelial cells.
AB  - BACKGROUND: The role of HNF4alpha has been extensively studied in hepatocytes and
      pancreatic beta-cells, and HNF4alpha is also regarded as a key regulator of
      intestinal epithelial cell differentiation. The aim of the present work is to
      identify novel HNF4alpha target genes in the human intestinal epithelial cells in
      order to elucidate the role of HNF4alpha in the intestinal differentiation
      progress. METHODS: We have performed a ChIP-chip analysis of the human intestinal
      cell line Caco-2 in order to make a genome-wide identification of HNF4alpha
      binding to promoter regions. The HNF4alpha ChIP-chip data was matched with gene
      expression and histone H3 acetylation status of the promoters in order to
      identify HNF4alpha binding to actively transcribed genes with an open chromatin
      structure. RESULTS: 1,541 genes were identified as potential HNF4alpha targets,
      many of which have not previously been described as being regulated by HNF4alpha.
      The 1,541 genes contributed significantly to gene ontology (GO) pathways
      categorized by lipid and amino acid transport and metabolism. An analysis of the
      homeodomain transcription factor Cdx-2 (CDX2), the disaccharidase trehalase
      (TREH), and the tight junction protein cingulin (CGN) promoters verified that
      these genes are bound by HNF4alpha in Caco2 cells. For the Cdx-2 and trehalase
      promoters the HNF4alpha binding was verified in mouse small intestine epithelium.
      CONCLUSION: The HNF4alpha regulation of the Cdx-2 promoter unravels a
      transcription factor network also including HNF1alpha, all of which are
      transcription factors involved in intestinal development and gene expression.

PMID- 19761588
TI  - Religiosity and teen birth rate in the United States.
AB  - BACKGROUND: The children of teen mothers have been reported to have higher rates
      of several unfavorable mental health outcomes. Past research suggests several
      possible mechanisms for an association between religiosity and teen birth rate in
      communities. METHODS: The present study compiled publicly accessible data on
      birth rates, conservative religious beliefs, income, and abortion rates in the
      U.S., aggregated at the state level. Data on teen birth rates and abortion
      originated from the Center for Disease Control; on income, from the U.S. Bureau
      of the Census, and on religious beliefs, from the U.S. Religious Landscape Survey
      carried out by the Pew Forum on Religion and Public Life. We computed
      correlations and partial correlations. RESULTS: Increased religiosity in
      residents of states in the U.S. strongly predicted a higher teen birth rate, with
      r = 0.73 (p < 0.0005). Religiosity correlated negatively with median household
      income, with r = -0.66, and income correlated negatively with teen birth rate,
      with r = -0.63. But the correlation between religiosity and teen birth rate
      remained highly significant when income was controlled for via partial
      correlation: the partial correlation between religiosity and teen birth rate,
      controlling for income, was 0.53 (p < 0.0005). Abortion rate correlated
      negatively with religiosity, with r = -0.45, p = 0.002. However, the partial
      correlation between teen birth rate and religiosity remained high and significant
      when controlling for abortion rate (partial correlation = 0.68, p < 0.0005) and
      when controlling for both abortion rate and income (partial correlation = 0.54, p
      = 0.001). CONCLUSION: With data aggregated at the state level, conservative
      religious beliefs strongly predict U.S. teen birth rates, in a relationship that
      does not appear to be the result of confounding by income or abortion rates. One
      possible explanation for this relationship is that teens in more religious
      communities may be less likely to use contraception.

PMID- 19761589
TI  - Consensus on gut feelings in general practice.
AB  - BACKGROUND: General practitioners sometimes base clinical decisions on gut
      feelings alone, even though there is little evidence of their diagnostic and
      prognostic value in daily practice. Research to validate the determinants and to
      assess the test properties of gut feelings requires precise and valid
      descriptions of gut feelings in general practice which can be used as a reliable
      measuring instrument. RESEARCH QUESTION: Can we obtain consensus on descriptions
      of two types of gut feelings: a sense of alarm and a sense of reassurance?
      METHODS: Qualitative research including a Delphi consensus procedure with a
      heterogeneous sample of 27 Dutch and Belgian GPs or ex-GPs involved in academic
      educational or research programmes. RESULTS: After four rounds, we found 70% or
      greater agreement on seven of the eleven proposed statements. A "sense of alarm"
      is defined as an uneasy feeling perceived by a GP as he/she is concerned about a
      possible adverse outcome, even though specific indications are lacking: There's
      something wrong here. This activates the diagnostic process by stimulating the GP
      to formulate and weigh up working hypotheses that might involve a serious
      outcome. A "sense of alarm" means that, if possible, the GP needs to initiate
      specific management to prevent serious health problems. A "sense of reassurance"
      is defined as a secure feeling perceived by a GP about the further management and
      course of a patient's problem, even though the doctor may not be certain about
      the diagnosis: Everything fits in. CONCLUSION: The sense of alarm and the sense
      of reassurance are well-defined concepts. These descriptions enable us to
      operationalise the concept of gut feelings in further research.

PMID- 19761590
TI  - Announcing the tumor immunology and biological cancer therapy section (edited by
      iSBTc) of the Journal of Translational Medicine.

PMID- 19761591
TI  - A web server for interactive and zoomable Chaos Game Representation images.
AB  - Chaos Game Representation (CGR) is a generalized scale-independent Markov
      transition table, which is useful for the visualization and comparative study of
      genomic signature, or for the study of characteristic sequence motifs. However,
      in order to fully utilize the scale-independent properties of CGR, it should be
      accessible through scale-independent user interface instead of static images.
      Here we describe a web server and Perl library for generating zoomable CGR images
      utilizing Google Maps API, which is also easily searchable for specific motifs.
      The web server is freely accessible at http://www.g-language.org/wiki/cgr/, and
      the Perl library as well as the source code is distributed with the G-language
      Genome Analysis Environment under GNU General Public License.

PMID- 19761592
TI  - Regression-based approach for testing the association between multi-region
      haplotype configuration and complex trait.
AB  - BACKGROUND: It is quite common that the genetic architecture of complex traits
      involves many genes and their interactions. Therefore, dealing with multiple
      unlinked genomic regions simultaneously is desirable. RESULTS: In this paper we
      develop a regression-based approach to assess the interactions of haplotypes that
      belong to different unlinked regions, and we use score statistics to test the
      null hypothesis of non-genetic association. Additionally, multiple marker
      combinations at each unlinked region are considered. The multiple tests are
      settled via the minP approach. The P value of the "best" multi-region multi
      marker configuration is corrected via Monte-Carlo simulations. Through simulation
      studies, we assess the performance of the proposed approach and demonstrate its
      validity and power in testing for haplotype interaction association. CONCLUSION:
      Our simulations showed that, for binary trait without covariates, our proposed
      methods prove to be equal and even more powerful than htr and hapcc which are
      part of the FAMHAP program. Additionally, our model can be applied to a wider
      variety of traits and allow adjustment for other covariates. To test the
      validity, our methods are applied to analyze the association between four
      unlinked candidate genes and pig meat quality.

PMID- 19761593
TI  - Influences of polymorphic variants of DRD2 and SLC6A3 genes, and their
      combinations on smoking in Polish population.
AB  - BACKGROUND: Polymorphisms in dopaminergic genes may influence cigarette smoking
      by their potential impact on dopamine reward pathway function. A1 allele of DRD2
      gene is associated with a reduced dopamine D2 receptor density, and it has been
      hypothesised that A1 carriers are more vulnerable to smoking. In turn, the 9
      repeat allele of dopamine transporter gene (SLC6A3) has been associated with a
      substantial reduction in dopamine transporter, what might result in the higher
      level of dopamine in the synaptic cleft, and thereby protective role of this
      allele from smoking. In the present study we investigated whether polymorphic
      variants of DRD2 and SLC6A3 genes and their combinations are associated with the
      smoking habit in the Polish population. METHODS: Genotyping for TaqIA
      polymorphism of DRD2 and SLC6A3 VNTR polymorphism was performed in 150 ever
      smokers and 158 never-smokers. The association between the smoking status and
      smoking phenotypes (related to the number of cigarettes smoked daily and age of
      starting regular smoking), and genotype/genotype combinations was expressed by
      ORs together with 95% CI. Alpha level of 0.05, with Bonferroni correction
      whenever appropriate, was used for statistical significance. RESULTS: At the used
      alpha levels no association between DRD2 and SLC6A3 genotypes and smoking status
      was found. However, A1 allele carriers reported longer abstinence periods on
      quitting attempts than non-carriers (p = 0.049). The ORs for heavier smoking were
      0.38 (0.17-0.88), p = 0.023, and 0.39 (0.17-0.88), p = 0.021 in carriers compared
      to non-carriers of A1 or *9 allele, respectively, and the OR for this smoking
      phenotype was 8.68 (2.47-30.46), p = 0.0005 for the A1-/9- genotype combination,
      relatively to the A1+/9+. Carriers of *9 allele of SLC6A3 had over twice a lower
      risk to start smoking before the age of 20 years compared to non-carriers (sex
      adjusted OR = 0.44; 95% CI: 0.22-0.89; p = 0.0017), and subjects with A1-/9-
      genotype combination had a higher risk for staring regular smoking before the age
      of 20 years in comparison to subjects with A1+/9+ genotype combination (sex
      adjusted OR = 3.79; 95% CI:1.03-13.90; p = 0.003). CONCLUSION: Polymorphic
      variants of DRD2 and SLC6A3 genes may influence some aspects of the smoking
      behavior, including age of starting regular smoking, the level of cigarette
      consumption, and periods of abstinence. Further large sample studies are needed
      to verify this hypothesis.

PMID- 19761594
TI  - A genetic algorithm based method for stringent haplotyping of family data.
AB  - BACKGROUND: The linkage phase, or haplotype, is an extra level of information
      that in addition to genotype and pedigree can be useful for reconstructing the
      inheritance pattern of the alleles in a pedigree, and computing for example
      Identity By Descent probabilities. If a haplotype is provided, the precision of
      estimated IBD probabilities increases, as long as the haplotype is estimated
      without errors. It is therefore important to only use haplotypes that are
      strongly supported by the available data for IBD estimation, to avoid introducing
      new errors due to erroneous linkage phases. RESULTS: We propose a genetic
      algorithm based method for haplotype estimation in family data that includes a
      stringency parameter. This allows the user to decide the error tolerance level
      when inferring parental origin of the alleles. This is a novel feature compared
      to existing methods for haplotype estimation. We show that using a high
      stringency produces haplotype data with few errors, whereas a low stringency
      provides haplotype estimates in most situations, but with an increased number of
      errors. CONCLUSION: By including a stringency criterion in our haplotyping
      method, the user is able to maintain the error rate at a suitable level for the
      particular study; one can select anything from haplotyped data with very small
      proportion of errors and a higher proportion of non-inferred haplotypes, to data
      with phase estimates for every marker, when haplotype errors are tolerable.
      Giving this choice makes the method more flexible and useful in a wide range of
      applications as it is able to fulfil different requirements regarding the
      tolerance for haplotype errors, or uncertain marker-phases.

PMID- 19761595
TI  - Prediction of coronary artery disease by a systemic atherosclerosis score index
      derived from whole-body MR angiography.
AB  - BACKGROUND: Whole-body magnetic resonance angiography (WB-MRA) has shown its
      potential for the non-invasive assessment of nearly the entire arterial
      vasculature within one examination. Since the presence of extra-cardiac
      atherosclerosis is associated with an increased risk of coronary events, our goal
      was to establish the relationship between WB-MRA findings, including a systemic
      atherosclerosis score index, and the presence of significant coronary artery
      disease (CAD). METHODS: WB-MRA was performed on a 1.5T scanner in 50 patients
      scheduled to undergo elective cardiac catheterization for suspected CAD. In each
      patient, 40 extra-cardiac vessel segments were evaluated and assigned scores
      according to their luminal narrowing. The atherosclerosis score index (ASI) was
      generated as the ratio of summed scores to analyzable segments. RESULTS: ASI was
      higher in patients with significant (> 50% stenosis) CAD (n = 27) vs. patients
      without CAD (n = 22; 1.56 vs. 1.28, p = 0.004). ASI correlated with PROCAM (R =
      0.57, p < 0.001) and Framingham (R = 0.36, p = 0.01) risk scores as estimates of
      the 10-year risk of coronary events. A ROC derived ASI of > 1.54 predicted
      significant CAD with a sensitivity of 59%, specificity of 86% and a positive
      predictive value of 84%. Logistic regression revealed ASI > 1.54 as the strongest
      independent predictor for CAD with a 11-fold increase in likelihood to suffer
      from significant coronary disease. On the contrary, while 15/27 (55%) of patients
      with CAD exhibited at least one extra-cardiac stenosis > 50%, only 3/22 (14%) of
      those patients without CAD did (p = 0.003). The likelihood for an extra-cardiac
      stenosis when CAD is present differed between vascular territories and ranged
      from 15% for a carotid stenosis to 44% for a stenosis in the lower extremities.
      CONCLUSION: This study provides important new evidence for the close association
      of extra-cardiac and coronary atherosclerosis. The novel findings that a WB-MRA
      derived systemic atherosclerosis score index is not only associated with
      established cardiovascular risk scores but is also predictive of significant CAD
      suggest its potential prognostic implications and underline the importance to
      screen for coronary disease in patients with extra-cardiac manifestations of
      atherosclerosis.

PMID- 19761596
TI  - How risky is caring for emergency patients at risk of malpractice litigation: a
      population based epidemiological study of Taiwan's experiences.
AB  - BACKGROUND: Emergency medicine has generally been considered a high risk
      specialty. The purpose of this study is to assess the risk of being sued in the
      district courts for caring emergency room (ER) patients from the perspective of
      epidemiology. METHODS: This research was designed to be a retrospective
      population based cohort study. We intended to find out the incidence of
      litigations arising from ER patients and that of birth inpatients in Taiwan, and
      computed their relative risks. The inclusion criterion was set to be incidents
      transpired in the time period of 1998 to 2002. The study materials included the
      reimbursement claim dataset of the National Health Insurance from 1998 to 2002,
      and the district court decision database of the Judicial Yuan from 1999 to 2006.
      RESULTS: The average annual incidence rate of becoming a plaintiff for ER
      patients is 0.86 per million, and for birth patients is 33.5 per million. There
      is a statistically significant difference between birth patients and ER patients.
      The relative risk comparing ER patients against birth inpatients is 0.03.
      CONCLUSION: The findings of this population based study indicate that the patient
      population emergency physicians are facing in Taiwan have relatively lower risks
      of developing litigation in comparison with the patients that come to give birth.
      Due to the large volume of ER patients, malpractice still pose a major threat in
      the emergency department, and misdiagnosis remains the major complaint of
      plaintiffs in subsequent litigations.

PMID- 19761597
TI  - CKD classification based on estimated GFR over three years and subsequent cardiac
      and mortality outcomes: a cohort study.
AB  - BACKGROUND: It is unknown whether defining chronic kidney disease (CKD) based on
      one versus two estimated glomerular filtration rate (eGFR) assessments changes
      the prognostic importance of reduced eGFR in a community-based population.
      METHODS: Participants in the Atherosclerosis Risk in Communities Study and the
      Cardiovascular Health Study were classified into 4 groups based on two eGFR
      assessments separated by 35.3 +/- 2.5 months: sustained eGFR < 60 mL/min per 1.73
      m(2) (1 mL/sec per 1.73 m(2)); eGFR increase (change from below to above 60);
      eGFR decline (change from above to below 60); and eGFR persistently >or=60.
      Outcomes assessed in stratified multivariable Cox models included cardiac events
      and a composite of cardiac events, stroke, and mortality. RESULTS: There were 891
      (4.9%) participants with sustained eGFR < 60, 278 (1.5%) with eGFR increase, 972
      (5.4%) with eGFR decline, and 15,925 (88.2%) with sustained eGFR > 60.
      Participants with eGFR sustained < 60 were at highest risk of cardiac and
      composite events [HR = 1.38 (1.15, 1.65) and 1.58 (1.41, 1.77)], respectively,
      followed by eGFR decline [HR = 1.20 (1.00, 1.45) and 1.32 (1.17, 1.49)].
      Individuals with eGFR increase trended toward increased cardiac risk [HR = 1.25
      (0.88, 1.77)] and did not significantly differ from eGFR decline for any outcome.
      Results were similar when estimating GFR with the CKD-EPI equation. CONCLUSION:
      Individuals with persistently reduced eGFR are at highest risk of cardiovascular
      outcomes and mortality, while individuals with an eGFR < 60 mL/min per 1.73 m(2)
      at any time are at intermediate risk. Use of even a single measurement of eGFR to
      classify CKD in a community population appears to have prognostic value.

PMID- 19761598
TI  - Factors affecting awareness of emergency contraception among college students in
      Kathmandu, Nepal.
AB  - BACKGROUND: In Nepal, Emergency Contraception (EC) could play a critical role in
      reducing unintended pregnancies, but very few people aware about it. This paper
      aims to investigate the level of awareness and factors influencing awareness of
      EC among college students. METHODS: A cross-sectional study was carried out in
      April-May 2006. Structured self-administered questionnaires were administered to
      1,137 college students (573 males and 564 females) in Kathmandu valley. The
      association between awareness of EC and the explanatory variables were first
      assessed in bivariate analysis using the Chi-square test. The associations were
      further explored using a multivariate logistic analysis. RESULTS: Only about two
      thirds of college students (68%) had ever heard about EC. Bivariate analysis
      shows that males were more aware (72%) of EC than were females (64%). Similarly,
      the awareness level was significantly higher among younger, unmarried youth who
      were from outside Kathmandu Valley, who lived with friends, and who had received
      reproductive health (RH) education in school/college. The study also found that
      students' sex, permanent place of residence (district), and RH education are
      significant predictors of awareness of EC. Males are 1.5 times more likely to be
      aware of EC compared to females. Furthermore, students who lived in Kathmandu
      Valley were 41% less likely to be aware of EC than were students from outside
      Kathmandu Valley. On the other hand, those students who received RH education in
      school/college were almost nine times more likely to be aware of EC compared to
      those who did not receive such education. CONCLUSION: Awareness of the EC is low
      among college students in Nepal. Health education initiatives should target
      students as they are more likely to be sexually active. There is a need to
      further educate students about EC which can help to reduce unintended
      pregnancies, many of which result in unsafe abortion and take a large toll on
      women's health.

PMID- 19761599
TI  - Termite usage associated with antibiotic therapy: enhancement of aminoglycoside
      antibiotic activity by natural products of Nasutitermes corniger (Motschulsky
      1855).
AB  - BACKGROUND: Several species from Insecta are used as remedies. Among these
      species, the termite Nasutitermes corniger is commonly used in traditional
      medicine in Northeast Brazil. The present work tests the modifying antibiotic
      activity of Nasutitermes corniger, a termite used in folk medicine in
      Northeastern region of Brazil. METHODS: Chlorpromazine and decocts of N. corniger
      were collected from two different plant species used in the traditional medicine
      were tested for their antimicrobial activity against strains of Escherichia coli
      resistant to aminoglycosides. The growth of two bacterial strains of E. coli was
      tested using decocts and chlorpromazine alone or associeted with aminogycosides.
      RESULTS: The MIC and MBC values were > or =1024 microg/ml for both strains of E.
      coli assayed. A significant synergism was observed between both decocts and
      chlorpromazine when assyed with neomycin. This synergism with neomycin indicates
      the involvement of an efflux system in the resistance to this aminoglycoside.
      CONCLUSION: Therefore it is suggested that natural products from N. corniger
      could be used as a source of zoo-derived natural products with modifying
      antibiotic activity to aminoglycosides, being a new weapon against the bacterial
      resistance to antibiotics.

PMID- 19761600
TI  - Paranoid atmospheres: psychiatric knowledge and delusional realities.
AB  - In this paper I investigate the topic of paranoid atmospheres. This subject is
      especially of interest with respect to persons who are deluded, and also, I will
      demonstrate, sheds light upon the psychiatrist's "gaze" and knowledge of
      delusions. In my argument I will follow a path initially outlined by Karl Jaspers
      (1883-1969): modern psychiatric diagnosis of delusions is a diagnosis of form and
      not content. Jaspers' emphasis on the form of delusions enables psychiatrists to
      be self-critical about their professional knowledge and, consequently, prevent
      the development of dogmatic attitudes. In accord with Jaspers, my argument will
      focus on the basic structure of delusions and highlight the difference between
      delusional realities and non-delusional realities, a difference that follows from
      the possibility of self-criticism of one's own conscious and explicit
      convictions. I will demonstrate the importance of self-criticism with regard to
      paranoid atmospheres and also to psychiatric knowledge. In this manner, an
      understanding of delusions as lived experience will be developed, which argues
      that an escalation of the influence of delusional convictions, resulting in a
      profoundly paranoid atmosphere, is most problematic for the deluded person. To
      acknowledge this insight mirrors the need for a self-critique of psychiatric
      discourse, encourages an empathic and respectful relationship between
      professionals and deluded patients, and enables deluded persons to restrict their
      paranoid atmosphere. It is the main conclusion of my paper that a deluded person
      cannot do (with respect to his delusional convictions) what a psychiatrist must
      do (with respect to his psychiatric knowledge and his own existential
      convictions) in order to prevent a profoundly paranoid atmosphere in their
      relationship: be self-critical.

PMID- 19761601
TI  - Potential for Raman spectroscopy to provide cancer screening using a peripheral
      blood sample.
AB  - Cancer poses a massive health burden with incidence rates expected to double
      globally over the next decade. In the United Kingdom screening programmes exists
      for cervical, breast, and colorectal cancer. The ability to screen individuals
      for solid malignant tumours using only a peripheral blood sample would
      revolutionise cancer services and permit early diagnosis and intervention. Raman
      spectroscopy interrogates native biochemistry through the interaction of light
      with matter, producing a high definition biochemical 'fingerprint' of the target
      material. This paper explores the possibility of using Raman spectroscopy to
      discriminate between cancer and non-cancer patients through a peripheral blood
      sample. Forty blood samples were obtained from patients with Head and Neck cancer
      and patients with respiratory illnesses to act as a positive control. Raman
      spectroscopy was carried out on all samples with the resulting spectra being used
      to build a classifier in order to distinguish between the cancer and respiratory
      patients' spectra; firstly using principal component analysis (PCA)/linear
      discriminant analysis (LDA), and secondly with a genetic evolutionary algorithm.
      The PCA/LDA classifier gave a 65% sensitivity and specificity for discrimination
      between the cancer and respiratory groups. A sensitivity score of 75% with a
      specificity of 75% was achieved with a 'trained' evolutionary algorithm. In
      conclusion this preliminary study has demonstrated the feasibility of using Raman
      spectroscopy in cancer screening and diagnostics of solid tumours through a
      peripheral blood sample. Further work needs to be carried out for this technique
      to be implemented in the clinical setting.

PMID- 19761602
TI  - Locations and patterns of meiotic recombination in two-generation pedigrees.
AB  - BACKGROUND: Meiotic crossovers are the major mechanism by which haplotypes are
      shuffled to generate genetic diversity. Previously available methods for the
      genome-wide, high-resolution identification of meiotic crossover sites are
      limited by the laborious nature of the assay (as in sperm typing). METHODS:
      Several methods have been introduced to identify crossovers using high density
      single nucleotide polymorphism (SNP) array technologies, although programs are
      not widely available to implement such analyses. RESULTS: Here we present a two
      generation "reverse pedigree analysis" method (analyzing the genotypes of two
      children relative to each parent) and a web-accessible tool to determine and
      visualize inheritance differences among siblings and crossover locations on each
      parental gamete. This approach is complementary to existing methods and uses
      informative markers which provide high resolution for locating meiotic crossover
      sites. We introduce a segmentation algorithm to identify crossover sites, and
      used a synthetic data set to determine that the segmentation algorithm
      specificity was 92% and sensitivity was 89%. The use of reverse pedigrees allows
      the inference of crossover locations on the X chromosome in a maternal gamete
      through analysis of two sons and their father. We further analyzed genotypes from
      eight multiplex autism families, observing a 1.462 maternal to paternal
      recombination ratio and no significant differences between affected and
      unaffected children. Meiotic recombination results from pediSNP can also be used
      to identify haplotypes that are shared by probands within a pedigree, as we
      demonstrated with a multiplex autism family. CONCLUSION: Using "reverse
      pedigrees" and defining unique sets of genotype markers within pedigree data, we
      introduce a method that identifies inherited allelic differences and meiotic
      crossovers. We implemented the method in the pediSNP software program, and we
      applied it to several data sets. This approach uses data from two generations to
      identify crossover sites, facilitating studies of recombination in disease.
      pediSNP is available online at http://pevsnerlab.kennedykrieger.org/pediSNP.

PMID- 19761603
TI  - Emotional intelligence and perceived stress in healthcare students: a multi
      institutional, multi-professional survey.
AB  - BACKGROUND: Emotional intelligence (EI) is increasingly discussed as having a
      potential role in medicine, nursing, and other healthcare disciplines, both for
      personal mental health and professional practice. Stress has been identified as
      being high for students in healthcare courses. This study investigated whether EI
      and stress differed among students in four health professions (dental, nursing,
      graduate mental health workers, medical) and whether there was evidence that EI
      might serve as a buffer for stress. METHOD: The Schutte Emotional Intelligence
      and the Perceived Stress scale instruments were administered to four groups of
      healthcare students in their first year of study in both the autumn and summer
      terms of the 2005-6 academic year. The groups were undergraduate dental, nursing
      and medical students, and postgraduate mental health workers. RESULTS: No
      significant differences were found between males and females nor among
      professional groups for the EI measure. Dental students reported significantly
      higher stress than medical students. EI was found to be only moderately stable in
      test-retest scores. Some evidence was found for EI as a possible factor in
      mediating stress. Students in different health profession courses did not show
      significant differences in Emotional Intelligence. CONCLUSION: While stress and
      EI showed a moderate relationship, results of this study do not allow the
      direction of relationship to be determined. The limitations and further research
      questions raised in this study are discussed along with the need for refinement
      of the EI construct and measures, particularly if Emotional Intelligence were to
      be considered as a possible selection criterion, as has been suggested by some
      authors.

PMID- 19761604
TI  - Temporal and geographic heterogeneity of the association between socioeconomic
      position and hospitalisation in Italy: an income based indicator.
AB  - BACKGROUND: The inverse association between socioeconomic position (SEP) and
      health has been extensively explored in Italy; however few studies have been
      carried out on the relationship between income inequalities and health status or
      health services utilisation, particularly at a local level.The objective of this
      study is to test the association between the demand for hospital care and a small
      area indicator based on income in four Italian cities, over a four-year period
      (1997-2000), in the adult population. METHODS: Census Block (median 260
      residents) Median per capita Income (CBMI) was computed through record linkage
      between 1998 national tax and local population registries in the cities of Rome,
      Turin, Milan and Bologna (total population approximately 5.5 million). CBMI was
      linked to acute hospital discharges among residents, based on patient's
      residence.Age-standardized gender-specific hospitalisation rates were computed by
      CBMI quintiles (first quintile indicating lowest income), overall, and by city
      and year. Heterogeneity of the association between income level and
      hospitalisation was analysed through a Poisson model. RESULTS: We found an
      inverse association between small area income level and hospitalisation rates,
      which decreased continuously from 153 per 1000 inhabitants in the first quintile
      to 107 per 1000 inhabitants in the fifth quintile. Income differences in
      hospitalisation were confirmed in each city and year. However, the magnitude of
      the association and the absolute level of hospitalisation rates were quite
      different in each city and tended to slightly decrease over time in all cities
      considered, except Bologna. CONCLUSION: Our study confirms an inverse association
      between income level and the use of hospitalization in four Italian cities, using
      a small area economic indicator, based on population tax data. Further analysis
      of the association between income and cause-specific hospitalization rates will
      allow to better understand the capability of the Italian National Health System
      to compel with socio-economic inequalities in health needs.Furthermore the SEP
      indicator we propose can represent a contribution to the improvement of tools for
      monitoring inequalities in health and in health services utilization.

PMID- 19761605
TI  - A potentially novel overlapping gene in the genomes of Israeli acute paralysis
      virus and its relatives.
AB  - The Israeli acute paralysis virus (IAPV) is a honeybee-infecting virus that was
      found to be associated with colony collapse disorder. The IAPV genome contains
      two genes encoding a structural and a nonstructural polyprotein. We applied a
      recently developed method for the estimation of selection in overlapping genes to
      detect purifying selection and, hence, functionality. We provide evolutionary
      evidence for the existence of a functional overlapping gene, which is translated
      in the +1 reading frame of the structural polyprotein gene. Conserved orthologs
      of this putative gene, which we provisionally call pog (predicted overlapping
      gene), were also found in the genomes of a monophyletic clade of dicistroviruses
      that includes IAPV, acute bee paralysis virus, Kashmir bee virus, and Solenopsis
      invicta (red imported fire ant) virus 1.

PMID- 19761606
TI  - Pessaries in multiple pregnancy as a prevention of preterm birth: the ProTwin
      Trial.
AB  - BACKGROUND: Multiple pregnancies are at high risk for preterm birth, and
      therefore an important cause of infant mortality and morbidity. A pessary is a
      simple and potentially effective measure for the prevention of preterm birth.
      Small studies have indicated its effectiveness, but large studies with sufficient
      power on the subject are lacking. Despite this lack of evidence, the treatment is
      at present applied by some gynaecologists in The Netherlands. METHODS/DESIGN: We
      aim to investigate the hypothesis that prophylactic use of a cervical pessary
      will be effective in the prevention of preterm delivery and the neonatal
      mortality and morbidity resulting from preterm delivery in multiple pregnancy. We
      will evaluate the costs and effects of this intervention. At study entry,
      cervical length will be measured. Eligible women will be randomly allocated to
      receive either a cervical pessary or no intervention. The cervical pessary will
      be placed in situ at 16 to 20 weeks, and will stay in situ up to 36 weeks
      gestation or until delivery, whatever comes first.The primary outcome is
      composite bad neonatal condition (perinatal death or severe morbidity). Secondary
      outcome measures are time to delivery, preterm birth rate before 32 and 37 weeks,
      days of admission in neonatal intensive care unit, maternal morbidity, maternal
      admission days for preterm labour and costs. We need to include 660 women to
      indicate a reduction in bad neonatal outcome from 7.2% without to 3.9% with a
      cervical pessary, using a two-sided test with an alpha of 0.05 and a power of
      0.80. DISCUSSION: This trial will provide evidence on whether a cervical pessary
      will decrease the incidence of early preterm birth and its concomitant bad
      neonatal outcome in multiple pregnancies. TRIAL REGISTRATION: Current Controlled
      Trials: NTR 1858.

PMID- 19761607
TI  - Detecting purely epistatic multi-locus interactions by an omnibus permutation
      test on ensembles of two-locus analyses.
AB  - BACKGROUND: Purely epistatic multi-locus interactions cannot generally be
      detected via single-locus analysis in case-control studies of complex diseases.
      Recently, many two-locus and multi-locus analysis techniques have been shown to
      be promising for the epistasis detection. However, exhaustive multi-locus
      analysis requires prohibitively large computational efforts when problems involve
      large-scale or genome-wide data. Furthermore, there is no explicit proof that a
      combination of multiple two-locus analyses can lead to the correct identification
      of multi-locus interactions. RESULTS: The proposed 2LOmb algorithm performs an
      omnibus permutation test on ensembles of two-locus analyses. The algorithm
      consists of four main steps: two-locus analysis, a permutation test, global p
      value determination and a progressive search for the best ensemble. 2LOmb is
      benchmarked against an exhaustive two-locus analysis technique, a set association
      approach, a correlation-based feature selection (CFS) technique and a tuned
      ReliefF (TuRF) technique. The simulation results indicate that 2LOmb produces a
      low false-positive error. Moreover, 2LOmb has the best performance in terms of an
      ability to identify all causative single nucleotide polymorphisms (SNPs) and a
      low number of output SNPs in purely epistatic two-, three- and four-locus
      interaction problems. The interaction models constructed from the 2LOmb outputs
      via a multifactor dimensionality reduction (MDR) method are also included for the
      confirmation of epistasis detection. 2LOmb is subsequently applied to a type 2
      diabetes mellitus (T2D) data set, which is obtained as a part of the UK genome
      wide genetic epidemiology study by the Wellcome Trust Case Control Consortium
      (WTCCC). After primarily screening for SNPs that locate within or near 372
      candidate genes and exhibit no marginal single-locus effects, the T2D data set is
      reduced to 7,065 SNPs from 370 genes. The 2LOmb search in the reduced T2D data
      reveals that four intronic SNPs in PGM1 (phosphoglucomutase 1), two intronic SNPs
      in LMX1A (LIM homeobox transcription factor 1, alpha), two intronic SNPs in PARK2
      (Parkinson disease (autosomal recessive, juvenile) 2, parkin) and three intronic
      SNPs in GYS2 (glycogen synthase 2 (liver)) are associated with the disease. The
      2LOmb result suggests that there is no interaction between each pair of the
      identified genes that can be described by purely epistatic two-locus interaction
      models. Moreover, there are no interactions between these four genes that can be
      described by purely epistatic multi-locus interaction models with marginal two
      locus effects. The findings provide an alternative explanation for the aetiology
      of T2D in a UK population. CONCLUSION: An omnibus permutation test on ensembles
      of two-locus analyses can detect purely epistatic multi-locus interactions with
      marginal two-locus effects. The study also reveals that SNPs from large-scale or
      genome-wide case-control data which are discarded after single-locus analysis
      detects no association can still be useful for genetic epidemiology studies.

PMID- 19761608
TI  - Phase Coupled Meta-analysis: sensitive detection of oscillations in cell cycle
      gene expression, as applied to fission yeast.
AB  - BACKGROUND: Many genes oscillate in their level of expression through the cell
      division cycle. Previous studies have identified such genes by applying Fourier
      analysis to cell cycle time course experiments. Typically, such analyses generate
      p-values; i.e., an oscillating gene has a small p-value, and the observed
      oscillation is unlikely due to chance. When multiple time course experiments are
      integrated, p-values from the individual experiments are combined using classical
      meta-analysis techniques. However, this approach sacrifices information inherent
      in the individual experiments, because the hypothesis that a gene is regulated
      according to the time in the cell cycle makes two independent predictions: first,
      that an oscillation in expression will be observed; and second, that gene
      expression will always peak in the same phase of the cell cycle, such as S-phase.
      Approaches that simply combine p-values ignore the second prediction. RESULTS:
      Here, we improve the detection of cell cycle oscillating genes by systematically
      taking into account the phase of peak gene expression. We design a novel meta
      analysis measure based on vector addition: when a gene peaks or troughs in all
      experiments in the same phase of the cell cycle, the representative vectors add
      to produce a large final vector. Conversely, when the peaks in different
      experiments are in various phases of the cycle, vector addition produces a small
      final vector. We apply the measure to ten genome-wide cell cycle time course
      experiments from the fission yeast Schizosaccharomyces pombe, and detect many
      new, weakly oscillating genes. CONCLUSION: A very large fraction of all genes in
      S. pombe, perhaps one-quarter to one-half, show some cell cycle oscillation,
      although in many cases these oscillations may be incidental rather than adaptive.

PMID- 19761609
TI  - Surgical treatment of a giant tibial high-grade mixofibrosarcoma with
      preservation of limb function: a case report.
AB  - Myxofibrosarcoma is one of the most common sarcomas in elderly patients showing
      a slight male prevalence. The tumor is mainly located in lower and upper
      extremities and rarely in trunk, neck and feet. We present a case of a 84-year
      old man referred to our tumour center with a giant and neglected high-grade
      tibial myxofibrosarcoma in the anteromedial side of tibial mid-diaphysis. Large
      size lesions in association with older age may jeopardise the maintenance of limb
      vitality, vascularity and stability.Authors performed a complete tumour
      resection, followed by reconstruction of bone and soft tissue defects with
      cement, plate and a musculocutaneous gastrocnemius flap, in order to cover the
      underlying bone and promote uneventful healing and perfusion of the operated
      extremity.At 2 years postoperatively, limb salvage, good functional outcome and
      no tumour recurrence were reported while the patient was able to effectively
      perform the majority of the daily activities.

PMID- 19761610
TI  - Myocardial ischemia with left ventricular outflow obstruction.
AB  - We report an unusual case of a 32-year old man who was treated for a hypertrophic
      obstructive cardiomyopathy (HOCM) with a DDD pacing with short AV delay reduction
      in the past. Without prior notice the patient developed ventricular fibrillation
      and an invasive cardiac diagnostic was performed, which revealed a myocardial
      bridging around of the left anterior descending artery (LAD). We suspected
      ischemia that could be either related to LAD artery compression or perfusion
      abnormalities due to AV delay reduction with related to diastolic dysfunction.

PMID- 19761611
TI  - Simultaneous alignment of short reads against multiple genomes.
AB  - Genome resequencing with short reads generally relies on alignments against a
      single reference. GenomeMapper supports simultaneous mapping of short reads
      against multiple genomes by integrating related genomes (e.g., individuals of the
      same species) into a single graph structure. It constitutes the first approach
      for handling multiple references and introduces representations for alignments
      against complex structures. Demonstrated benefits include access to polymorphisms
      that cannot be identified by alignments against the reference alone. Download
      GenomeMapper at http://1001genomes.org.

PMID- 19761612
TI  - Reciprocal regulation by the CepIR and CciIR quorum sensing systems in
      Burkholderia cenocepacia.
AB  - BACKGROUND: Burkholderia cenocepacia belongs to a group of closely related
      organisms called the B. cepacia complex (Bcc) which are important opportunistic
      human pathogens. B. cenocepacia utilizes a mechanism of cell-cell communication
      called quorum sensing to control gene expression including genes involved in
      virulence. The B. cenocepacia quorum sensing network includes the CepIR and CciIR
      regulatory systems. RESULTS: Global gene expression profiles during growth in
      stationary phase were generated using microarrays of B. cenocepacia cepR, cciR
      and cepRcciIR mutants. This is the first time CciR was shown to be a global
      regulator of quorum sensing gene expression. CepR was primarily responsible for
      positive regulation of gene expression while CciR generally exerted negative gene
      regulation. Many of the genes that were regulated by both quorum sensing systems
      were reciprocally regulated by CepR and CciR. Microarray analysis of the
      cepRcciIR mutant suggested that CepR is positioned upstream of CciR in the quorum
      sensing hierarchy in B. cenocepacia. A comparison of CepIR-regulated genes
      identified in previous studies and in the current study showed a substantial
      amount of overlap validating the microarray approach. Several novel quorum
      sensing-controlled genes were confirmed using qRT-PCR or promoter::lux fusions.
      CepR and CciR inversely regulated flagellar-associated genes, the nematocidal
      protein AidA and a large gene cluster on Chromosome 3. CepR and CciR also
      regulated genes required for iron transport, synthesis of extracellular enzymes
      and surface appendages, resistance to oxidative stress, and phage-related genes.
      CONCLUSION: For the first time, the influence of CciIR on global gene regulation
      in B. cenocepacia has been elucidated. Novel genes under the control of the CepIR
      and CciIR quorum sensing systems in B. cenocepacia have been identified. The two
      quorum sensing systems exert reciprocal regulation of many genes likely enabling
      fine-tuned control of quorum sensing gene expression in B. cenocepacia strains
      carrying the cenocepacia island.

PMID- 19761613
TI  - Gastric cancer: predictors of recurrence when lymph-node dissection is
      inadequate.
AB  - BACKGROUND: The TNM classification (sixth edition) requires at least 15 lymph
      nodes to be examined to allow an accurate staging. However, in our environment,
      only 20% of patients have the recommended minimum of 15 nodes removed. PURPOSE:
      To evaluate clinicopathological predictors of recurrence in patients with gastric
      cancer undergoing radical resection with an inadequate number of lymph nodes
      examined. METHODS: 101 patients were included in this retrospective cohort. We
      evaluated age, gender, tumoral location, Borrmann type, Lauren histotype, type of
      gastrectomy, grade, invasion depth of tumor, lymph node involvement, ratio
      between metastatic and total number of excised lymph nodes keeping 20% as the
      cutoff value (LNR) and adjuvant treatment. The association between these
      variables and recurrence was investigated by using univariate methods and
      multivariate logistic regression analysis. RESULTS: Median (range) age was 63
      years (44-85). 63% males, 37% females. Median follow-up time for the whole
      patients population was 36 months (10-104). Median number of lymph nodes
      retrieved was 6 (0-14). Recurrence: 50 of 101 cases (49,6%); 41 hematogeneus
      dissemination, 9 locoregional recurrences. The following factors were found to be
      correlated with the recurrence risk: tumoral location, invasion depth of tumor,
      lymph node involvement and LNR. A multivariate analysis revealed that depth of
      invasion [odds ratio (OR) 2.80, 95% confidence interval (CI) 1.03-7.58, P = 0.04]
      and LNR (OR 2.34, 95% CI 1.05-5.21, P = 0.03) were independent risk factors for
      recurrences of gastric cancer. Median time to recurrence: 16 months (2-50). 82%
      of recurrences occurred within the first two years after surgical treatment. The
      estimated cumulative risk of recurrence at five years: 61% in the whole patients
      population, with serosal invasion and LNR > and < 20% was 82% and 44%, without
      serosal invasion 73% and 39% respectively. CONCLUSION: Invasion depth of tumor
      and LNR were independent predictors of recurrence in gastric cancer after
      potentially curative resection with an inadequate number of lymph nodes examined.

PMID- 19761614
TI  - Using vital statistics to estimate the population-level impact of osteoporotic
      fractures on mortality based on death certificates, with an application to France
      (2000-2004).
AB  - BACKGROUND: We developed a methodology using vital statistics to estimate the
      impact of osteoporotic fractures on the mortality of an entire population, and
      applied it to France for the period 2000-2004. METHODS: Current definitions of
      osteoporotic fractures were reviewed and their components identified. We used the
      International Classification of Diseases with national vital statistics data for
      the French adult population and performed cross-classifications between various
      components: age, sex, I-code (site) and E-code (mechanism of fracture). This
      methodology allowed identification of appropriate thresholds and categorization
      for each pertinent component. RESULTS: 2,625,743 death certificates were
      analyzed, 2.2% of which carried a mention of fracture. Hip fractures represented
      55% of all deaths from fracture. Both sexes showed a similar pattern of mortality
      rates for all fracture sites, the rate increased with age from the age of 70
      years. The E-high-energy code (present in 12% of death certificates with
      fractures) was found to be useful to rule-out non-osteoporotic fractures, and to
      correct the overestimation of mortality rates. Using this methodology, the crude
      number of deaths associated with fractures was estimated to be 57,753 and the
      number associated with osteoporotic fractures 46,849 (1.85% and 1.78% of all
      deaths, respectively). CONCLUSION: Osteoporotic fractures have a significant
      impact on overall population mortality.

PMID- 19761615
TI  - A switchable light-input, light-output system modelled and constructed in yeast.
AB  - BACKGROUND: Advances in synthetic biology will require spatio-temporal regulation
      of biological processes in heterologous host cells. We develop a light
      switchable, two-hybrid interaction in yeast, based upon the Arabidopsis proteins
      PHYTOCHROME A and FAR-RED ELONGATED HYPOCOTYL 1-LIKE. Light input to this
      regulatory module allows dynamic control of a light-emitting LUCIFERASE reporter
      gene, which we detect by real-time imaging of yeast colonies on solid media.
      RESULTS: The reversible activation of the phytochrome by red light, and its
      inactivation by far-red light, is retained. We use this quantitative readout to
      construct a mathematical model that matches the system's behaviour and predicts
      the molecular targets for future manipulation. CONCLUSION: Our model, methods and
      materials together constitute a novel system for a eukaryotic host with the
      potential to convert a dynamic pattern of light input into a predictable gene
      expression response. This system could be applied for the regulation of genetic
      networks - both known and synthetic.

PMID- 19761616
TI  - The membrane mucin MUC4 is elevated in breast tumor lymph node metastases
      relative to matched primary tumors and confers aggressive properties to breast
      cancer cells.
AB  - INTRODUCTION: Previous studies indicate that overexpression of the membrane
      associated mucin MUC4 is potently anti-adhesive to cultured tumor cells, and
      suppresses cellular apoptotic response to a variety of insults. Such observations
      raise the possibility that MUC4 expression could contribute to tumor progression
      or metastasis, but the potential involvement of MUC4 in breast cancer has not
      been rigorously assessed. The present study aimed to investigate the expression
      of the membrane mucin MUC4 in normal breast tissue, primary breast tumors and
      lymph node metastases, and to evaluate the role of MUC4 in promoting the
      malignant properties of breast tumor cells. METHODS: MUC4 expression levels in
      patient-matched normal and tumor breast tissue was initially examined by
      immunoblotting lysates of fresh frozen tissue samples with a highly specific
      preparation of anti-MUC4 monoclonal antibody 1G8. Immunohistochemical analysis
      was then carried out using tissue microarrays encompassing patient-matched normal
      breast tissue and primary tumors, and patient-matched lymph node metastases and
      primary tumors. Finally, shRNA-mediated knockdown was employed to assess the
      contribution of MUC4 to the cellular growth and malignancy properties of JIMT-1
      breast cancer cells. RESULTS: Immunoblotting and immunohistochemistry revealed
      that MUC4 levels are suppressed in the majority (58%, p < 0.001) of primary
      tumors relative to patient-matched normal tissue. On the other hand, lymph node
      metastatic lesions from 37% (p < 0.05) of patients expressed higher MUC4 protein
      levels than patient-matched primary tumors. MUC4-positive tumor emboli were often
      found in lymphovascular spaces of lymph node metastatic lesions. shRNA-mediated
      MUC4 knockdown compromised the migration, proliferation and anoikis resistance of
      JIMT-1 cells, strongly suggesting that MUC4 expression actively contributes to
      cellular properties associated with breast tumor metastasis. CONCLUSIONS: Our
      observations suggest that after an initial loss of MUC4 levels during the
      transition of normal breast tissue to primary tumor, the re-establishment of
      elevated MUC4 levels confers an advantage to metastasizing breast tumor cells by
      promoting the acquisition of cellular properties associated with malignancy.

PMID- 19761617
TI  - Impact of female age and male infertility on ovarian reserve markers to predict
      outcome of assisted reproduction technology cycles.
AB  - BACKGROUND: This study was designed to assess the capability of ovarian reserve
      markers, including baseline FSH levels, baseline anti-Mullerian hormone (AMH)
      levels, and antral follicle count (AFC), as predictors of live births during IVF
      cycles, especially for infertile couples with advanced maternal age and/or male
      factors. METHODS: A prospective cohort of 336 first IVF/ICSI cycles undergoing a
      long protocol with GnRH agonist was investigated. Patients with endocrine
      disorders or unilateral ovaries were excluded. RESULTS: Among the ovarian reserve
      tests, AMH and age had a greater area under the receiving operating
      characteristic curve than FSH in predicting live births. Furthermore, AMH and age
      were the sole predictive factors of live births for women greater than or equal
      to 35 years of age; while AMH was the major determinant of live births for
      infertile couples with absence of male factors by multivariate logistic
      regression analysis. However, all the studied ovarain reserve tests were not
      preditive of live births for women < 35 years of age or infertile couples with
      male factors. CONCLUSION: The serum AMH levels were prognostic for pregnancy
      outcome for infertile couples with advanced female age or absence of male
      factors. The predictive capability of ovarian reserve tests is clearly influenced
      by the etiology of infertility.

PMID- 19761618
TI  - Efficacy of pharmacotherapies for short-term smoking abstinance: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Smoking cessation has important immediate health benefits. The
      comparative short-term effectiveness of smoking cessation interventions is not
      well known. We aimed to determine the relative effectiveness of nicotine
      replacement therapy (NRT), bupropion and varenicline at 4 weeks post-target quit
      date. METHODS: We searched 10 electronic medical databases (inception to October
      2008). We selected randomized clinical trials [RCTs] evaluating interventions for
      our primary outcome of abstinence from smoking at at-least 4 weeks post-target
      quit date, with biochemical confirmation. We conducted random-effects odds ratio
      (OR) meta-analysis and meta-regression. We compared treatment effects across
      interventions using head-to-head trials and calculated indirect comparisons.
      RESULTS: We combined a total of 101 trials evaluating delivery of NRT versus
      inert controls at approximately 4 weeks post-target quit date (total n = 31,321).
      The pooled overall OR is OR 2.05 (95% Confidence Interval [CI], 1.89-2.23, P =<
      0.0001). We pooled data from 31 bupropion trials contributing a total n of 11,118
      participants and found a pooled OR of 2.25 (95% CI, 1.94-2.62, P =< 0.0001). We
      evaluated 9 varenicline trials compared to placebo. Our pooled estimate for
      cessation at 4 weeks post-target quit date found a pooled OR of 3.16 (95% CI,
      2.55-3.91, P =< 0.0001). Two trials evaluated head to head comparisons of
      varenicline and bupropion and found a pooled estimate of OR 1.86 (95% CI, 1.49
      2.33, P =< 0.0001 at 4 weeks post-target quit date. Indirect comparisons were:
      NRT and bupropion, OR, 1.09, 95% CI, 0.93-1.31, P = 0.28; varenicline and NRT, OR
      1.56, 95% CI, 1.23-1.96, P = 0.0002; and, varenicline and bupropion, OR 1.40, 95%
      CI, 1.08-1.85, P = 0.01. CONCLUSION: Pharmacotherapeutic interventions are
      effective for increasing smoking abstinence rates in the short-term.

PMID- 19761619
TI  - Developing an award program for children's settings to support healthy eating and
      physical activity and reduce the risk of overweight and obesity.
AB  - BACKGROUND: This paper aimed to identify the best way to engage, motivate and
      support early childhood services (ECS) and primary schools (PS) to create policy
      and practise changes to promote healthy eating and physical activity. This
      information would be used to develop a suitable program to implement within these
      children's settings to reduce the risk of childhood overweight and obesity.
      METHODS: The Medical Research Council's (UK) framework for the design and
      evaluation of complex interventions was used to guide the development of the
      healthy eating and physical activity program suitable for ECS and PS. Within this
      framework a range of evaluation methods, including stakeholder planning, in-depth
      interviews with ECS and PS staff and acceptability and feasibility trials in one
      local government area, were used to ascertain the best way to engage and support
      positive changes in these children's settings. RESULTS: Both ECS and PS
      identified that they had a role to play to improve children's healthy eating and
      physical activity. ECS identified their role in promoting healthy eating and
      physical activity as important for children's health, and instilling healthy
      habits for life. PS felt that these were health issues, rather than educational
      issues; however, schools saw the link between healthy eating and physical
      activity and student learning outcomes. These settings identified that a program
      that provides a simple guide that recognises good practise in these settings,
      such as an award scheme using a health promoting schools approach, as a feasible
      and acceptable way for them to support children's healthy eating and physical
      activity. CONCLUSION: Through the process of design and evaluation a program -
      Kids - 'Go for your life', was developed to promote and support children's
      healthy eating and physical activity and reduce the risk of childhood overweight
      and obesity. Kids - 'Go for your life' used an award program, based on a health
      promoting schools approach, which was demonstrated to be a suitable model to
      engage ECS and PS and was acceptable and feasible to create policy and practise
      changes to support healthy eating and physical activity for children.

PMID- 19761620
TI  - Particulate matter and atherosclerosis: role of particle size, composition and
      oxidative stress.
AB  - Air Pollution has been associated with significant adverse health effects
      leading to increased morbidity and mortality. Cumulative epidemiological and
      experimental data have shown that exposure to air pollutants lead to increased
      cardiovascular ischemic events and enhanced atherosclerosis. It appears that
      these associations are much stronger with the air particulate matter (PM)
      component and that in urban areas, the smaller particles could be more
      pathogenic, as a result of their greater propensity to induce systemic prooxidant
      and proinflammatory effects. Much is still unknown about the toxicology of
      ambient particulates as well as the pathogenic mechanisms responsible for the
      induction of adverse cardiovascular health effects. It is expected that better
      understanding of these effects will have large implications and may lead to the
      formulation and implementation of new regulatory policies. Indeed, we have found
      that ultrafine particles (<0.18 mum) enhance early atherosclerosis, partly due to
      their high content in redox cycling chemicals and their ability to synergize with
      known proatherogenic mediators in the promotion of tissue oxidative stress. These
      changes take place in parallel with increased evidence of phase 2 enzymes
      expression, via the electrophile-sensitive transcription factor, p45-NFE2 related
      transcription factor 2 (Nrf2). Exposure to ultrafine particles also results in
      alterations of the plasma HDL anti-inflammatory function that could be indicative
      of systemic proatherogenic effects. This article reviews the epidemiological,
      clinical and experimental animal evidence that support the association of
      particulate matter with atherogenesis. It also discusses the possible pathogenic
      mechanisms involved, the physicochemical variables that may be of importance in
      the greater toxicity exhibited by a small particle size, interaction with genes
      and other proatherogenic factors as well as important elements to consider in the
      design of future mechanistic studies.Extensive epidemiological evidence supports
      the association of air pollution with adverse health effects 123. It is
      increasingly being recognized that such effects lead to enhanced morbidity and
      mortality, mostly due to exacerbation of cardiovascular diseases and
      predominantly those of ischemic character 4. Indeed, in addition to the classical
      risk factors such as serum lipids, smoking, hypertension, aging, gender, family
      history, physical inactivity and diet, recent data have implicated air pollution
      as an important additional risk factor for atherosclerosis. This has been the
      subject of extensive reviews 56 and a consensus statement from the American Heart
      Association 7. This article reviews the supporting epidemiological and animal
      data, possible pathogenic mechanisms and future perspectives.

PMID- 19761621
TI  - Quadruple 9-mer-based protein binding microarray with DsRed fusion protein.
AB  - BACKGROUND: The interaction between a transcription factor and DNA motif (cis
      acting element) is an important regulatory step in gene regulation. Comprehensive
      genome-wide methods have been developed to characterize protein-DNA interactions.
      Recently, the universal protein binding microarray (PBM) was introduced to
      determine if a DNA motif interacts with proteins in a genome-wide manner.
      RESULTS: We facilitated the PBM technology using a DsRed fluorescent protein and
      a concatenated sequence of oligonucleotides. The PBM was designed in such a way
      that target probes were synthesized as quadruples of all possible 9-mer
      combinations, permitting unequivocal interpretation of the cis-acting elements.
      The complimentary DNA strands of the features were synthesized with a primer and
      DNA polymerase on microarray slides. Proteins were labeled via N-terminal fusion
      with DsRed fluorescent protein, which circumvents the need for a multi-step
      incubation. The PBM presented herein confirmed the well-known DNA binding
      sequences of Cbf1 and CBF1/DREB1B, and it was also applied to elucidate the
      unidentified cis-acting element of the OsNAC6 rice transcription factor.
      CONCLUSION: Our method demonstrated PBM can be conveniently performed by
      adopting: (1) quadruple 9-mers may increase protein-DNA binding interactions in
      the microarray, and (2) a one-step incubation shortens the wash and hybridization
      steps. This technology will facilitate greater understanding of genome-wide
      interactions between proteins and DNA.

PMID- 19761622
TI  - Characterizing trends in HIV infection among men who have sex with men in
      Australia by birth cohorts: results from a modified back-projection method.
AB  - BACKGROUND: We set out to estimate historical trends in HIV incidence in
      Australian men who have sex with men with respect to age at infection and birth
      cohort. METHODS: A modified back-projection technique is applied to data from the
      HIV/AIDS Surveillance System in Australia, including "newly diagnosed HIV
      infections", "newly acquired HIV infections" and "AIDS diagnoses", to estimate
      trends in HIV incidence over both calendar time and age at infection. RESULTS:
      Our results demonstrate that since 2000, there has been an increase in new HIV
      infections in Australian men who have sex with men across all age groups. The
      estimated mean age at infection increased from ~35 years in 2000 to ~37 years in
      2007. When the epidemic peaked in the mid 1980s, the majority of the infections
      (56%) occurred among men aged 30 years and younger; 30% occurred in ages 31 to 40
      years; and only ~14% of them were attributed to the group who were older than 40
      years of age. In 2007, the proportion of infections occurring in persons 40 years
      or older doubled to 31% compared to the mid 1980s, while the proportion of
      infections attributed to the group younger than 30 years of age decreased to 36%.
      CONCLUSION: The distribution of HIV incidence for birth cohorts by infection year
      suggests that the HIV epidemic continues to affect older homosexual men as much
      as, if not more than, younger men. The results are useful for evaluating the
      impact of the epidemic across successive birth cohorts and study trends among the
      age groups most at risk.

PMID- 19761623
TI  - A case study of physical and social barriers to hygiene and child growth in
      remote Australian Aboriginal communities.
AB  - BACKGROUND: Despite Australia's wealth, poor growth is common among Aboriginal
      children living in remote communities. An important underlying factor for poor
      growth is the unhygienic state of the living environment in these communities.
      This study explores the physical and social barriers to achieving safe levels of
      hygiene for these children. METHODS: A mixed qualitative and quantitative
      approach included a community level cross-sectional housing infrastructure
      survey, focus groups, case studies and key informant interviews in one community.
      RESULTS: We found that a combination of crowding, non-functioning essential
      housing infrastructure and poor standards of personal and domestic hygiene
      underlie the high burden of infection experienced by children in this remote
      community. CONCLUSION: There is a need to address policy and the management of
      infrastructure, as well as key parenting and childcare practices that allow the
      high burden of infection among children to persist. The common characteristics of
      many remote Aboriginal communities in Australia suggest that these findings may
      be more widely applicable.

PMID- 19761624
TI  - Conjugated linoleic acids as functional food: an insight into their health
      benefits.
AB  - This review evaluates the health benefits of the functional food, conjugated
      linoleic acids (CLA) - a heterogeneous group of positional and geometric isomers
      of linoleic acid predominantly found in milk, milk products, meat and meat
      products of ruminants. During the past couple of decades, hundreds of reports -
      principally based on in vitro, microbial, animal, and of late clinical trials on
      humans - have been accumulating with varying biological activities of CLA
      isomers. These studies highlight that CLA, apart form the classical nuclear
      transcription factors-mediated mechanism of action, appear to exhibit a number of
      inter-dependent molecular signalling pathways accounting for their reported
      health benefits. Such benefits relate to anti-obesitic, anti-carcinogenic, anti
      atherogenic, anti-diabetagenic, immunomodulatory, apoptotic and osteosynthetic
      effects. On the other hand, negative effects of CLA have been reported such as
      fatty liver and spleen, induction of colon carcinogenesis and
      hyperproinsulinaemia. As far as human consumption is concerned, a definite
      conclusion for CLA safety has not been reached yet. Parameters such as
      administration of the type of CLA isomer and/or their combination with other
      polyunsaturated fatty acids, mode of administration (eg., as free fatty acid or
      its triglyceride form, liquid or solid), daily dose and duration of consumption,
      gender, age, or ethnic and geographical backgrounds remain to be determined. Yet,
      it appears from trials so far conducted that CLA are functional food having
      prevailing beneficial health effects for humans.

PMID- 19761625
TI  - Time trends in exposure of cattle to bovine spongiform encephalopathy and cohort
      effect in France and Italy: value of the classical Age-Period-Cohort approach.
AB  - BACKGROUND: The Age-Period-Cohort (APC) analysis is routinely used for time trend
      analysis of cancer incidence or mortality rates, but in veterinary epidemiology,
      there are still only a few examples of this application. APC models were recently
      used to model the French epidemic assuming that the time trend for BSE was mainly
      due to a cohort effect in relation to the control measures that may have modified
      the BSE exposure of cohorts over time. We used a categorical APC analysis which
      did not require any functional form for the effect of the variables, and examined
      second differences to estimate the variation of the BSE trend. We also reanalysed
      the French epidemic and performed a simultaneous analysis of Italian data using
      more appropriate birth cohort categories for comparison. RESULTS: We used data
      from the exhaustive surveillance carried out in France and Italy between 2001 and
      2007, and comparatively described the trend of the epidemic in both countries. At
      the end, the shape and irregularities of the trends were discussed in light of
      the main control measures adopted to control the disease. In Italy a decrease in
      the epidemic became apparent from 1996, following the application of rendering
      standards for the processing of specific risk material (SRM). For the French
      epidemic, the pattern of second differences in the birth cohorts confirmed the
      beginning of the decrease from 1995, just after the implementation of the meat
      and bone meal (MBM) ban for all ruminants (1994). CONCLUSION: The APC analysis
      proved to be highly suitable for the study of the trend in BSE epidemics and was
      helpful in understanding the effects of management and control of the disease.
      Additionally, such an approach may help in the implementation of changes in BSE
      regulations.

PMID- 19761626
TI  - Infection of Mytilus edulis by the trematode Echinostephilla patellae (Digenea:
      Philophthalmidae).
AB  - The blue mussel Mytilus edulis is described as second intermediate host for
      Echinostephilla patellae from the common limpet Patella vulgata. Mussels were
      infected with metacercariae of E. patellae under laboratory conditions. Average
      infection rates increased with increasing temperature, whereas numbers of
      cercariae, to which individual mussels were exposed, had no effect on relative
      infection success. The round to slightly oval metacercariae with an average cyst
      diameter of 208 microm (range 186-243 microm) encysted exclusively in the foot
      tissue of M. edulis. Morphologically similar metacercariae were found in
      naturally infected mussels at sites where parasitized P. vulgata and M. edulis
      are sympatric. This is the first report of E. patellae in blue mussels. The
      detection of M. edulis being a second intermediate host is of particular interest
      with regard to the abundance of the parasite and host organisms in intertidal
      rocky shore ecosystems. The potential role of the common limpet P. vulgata as an
      alternative secondary host is discussed.

PMID- 19761627
TI  - Sex ratio and morphological polymorphism in an isolated, endemic Teladorsagia
      circumcincta population.
AB  - Teladorsagia circumcincta is a polygamous nematode that exhibits morphological
      polymorphism. Sex ratio is typically female biased and the male nematodes occur
      in association with the genetically similar, minor morphotypes Teladorsagia
      davtiani and Teladorsagia trifurcata. In experimental infections, sex ratio
      (proportion male) and the proportion of minor male morphs observed have been
      shown to be influenced by both host and nematode-related factors. As similar
      investigations from natural systems are rare, this study examined whether sex
      ratio and minor male morph frequency were associated with host age and sex and
      nematode infra-population size in the isolated Soay sheep population on St Kilda.
      Count data for Teladorsagia were analysed for sheep of all age classes and both
      sexes from the winters of three consecutive population crashes (1999, 2002 and
      2005). Generally, the intensity of Teladorsagia nematodes increased with host age
      until the age of 2 years before decreasing. In 2005, abundance of nematodes was
      generally higher than in the previous crashes, nematode sex ratio was negatively
      associated with host age and tended to be negatively associated with nematode
      intensity. Within the male nematode subpopulation, T. circumcincta always
      predominated, followed by T. davtiani and then T. trifurcata, with little
      variation in the relative proportions between hosts. The presence of each minor
      morph was primarily associated with the intensity of male T. circumcincta and, in
      those hosts where all three male morphs were detected, intensity of each minor
      morph was most associated with intensity of Teladorsagia females. Therefore, in a
      year when the nematode was generally more abundant, sex ratio appeared to be
      influenced by both host and nematode-related factors, whereas in all years
      examined, the frequency of morphological polymorphism was primarily density
      dependent.

PMID- 19761628
TI  - Diversity of metazoan parasites of the African catfish Clarias gariepinus
      (Burchell, 1822) as indicators of pollution in a subtropical African river
      system.
AB  - The relationship between parasite species diversity and organic pollution in the
      upper Manyame catchment, Zimbabwe, was investigated between October 2006 and
      January 2007. The parasite assemblage comprised 13 species in total. Species
      richness in the unpolluted sites was high; in the moderately polluted sites, it
      was low, while in the polluted sites, only one parasite species was encountered.
      Component community diversity, as measured by the Shannon index (H'), decreased
      with increase in organic pollution. The distribution and occurrence of
      ectoparasites (Dolops ranarum, Lamproglena clariae, Chonopeltis sp. and
      Macrogyrodactylus sp.) and one endoparasite (Lytocestus sp.) were limited to the
      unpolluted sites, demonstrating their sensitivity to organic pollution. The
      prevalence of the nematodes Paracamallanus cyathopharynx, Procamallanus
      laevionchus and Contracaecum spp. larvae decreased along the pollution gradient,
      showing their high sensitivity to organic pollution. The platyhelminths
      Diplostomum sp. and Polyonchobothrium clarias were the most tolerant and occurred
      at both polluted and unpolluted sites. Proteocephalus sp. and Caryophyllaeus sp.
      were limited to the polluted sites, probably as a result of high abundance of
      oligochaetes and copepods, their intermediate hosts that thrive in sewage
      enriched sediments, at the downstream sites. The observed results assume that the
      decrease in parasite diversity can be related to increased organic pollution.
      Some parasites requiring complex life histories were absent along with pollution
      related disappearance of their vector hosts. Further studies should address the
      identification of parasite life stages that are more sensitive to pollutants.

PMID- 19761629
TI  - An unexpected hysterosalpingographic finding.

PMID- 19761631
TI  - Going digital.

PMID- 19761633
TI  - Placental weight in pregnancies with trisomy confined to the placenta.
AB  - OBJECTIVE: Mosaicism with trisomy confined to the placenta is present in ~1% of
      ongoing pregnancies at the time of chorionic villus sampling. Some studies have
      found reduced fetal growth in confined placental trisomy. The objective of this
      study was to assess placental weight and feto-placental weight ratio in
      pregnancies with trisomy confined to the placenta, and to correlate them with the
      level of trisomy in the three major placental lineages. METHODS: We conducted a
      retrospective study of 69 pregnancies with prenatally diagnosed mosaic trisomy in
      which the trisomic cells were confined to the placenta. Placental weight and feto
      placental weight ratio were compared to those of matched controls, and placental
      weight was also analyzed for associations with the type and level of trisomy.
      Placental pathology was also reviewed. RESULTS: The pregnancies with mosaic
      trisomy were found to have lower placental weights than matched controls, but
      normal feto-placental weight ratios. Placental weight was not associated with the
      type or level of trisomic cells in the three placental lineages at term
      (chorionic plate, chorionic villus mesenchyme, and trophoblast). There were no
      pathognomonic findings on routine placental pathology of the trisomic placentas.
      CONCLUSION: Although placental weight was reduced (with normal feto-placental
      weight ratio) in pregnancies with trisomy confined to the placenta, the level of
      placental trisomy was not correlated with placental weight. Thus, trisomy may
      alter placental function rather than have a direct hypoplastic effect on
      placental growth. More in-depth studies beyond routine pathology are required to
      identify how trisomy affects placental function.

PMID- 19761634
TI  - Epidemiology of pregnancy-associated venous thromboembolism: a population-based
      study in Canada.
AB  - OBJECTIVE: To estimate the frequency of, and to identify risk factors for,
      pregnancy-associated venous thromboembolism (VTE), including deep vein thrombosis
      (DVT) and pulmonary embolism (PE) requiring hospitalization. METHODS: We
      conducted a population-based cohort study (N = 3 852 569) using the Discharge
      Abstract Database of the Canadian Institute for Health Information (CIHI), for
      the fiscal years 1991-1992 to 2005-2006. All women with pregnancy-related
      hospitalizations in Canada (excluding Quebec and Manitoba) were identified. DVT
      and PE rates were calculated using the number of hospital deliveries (i.e.,
      cohort of women at risk) as the denominator for the antepartum and peripartum
      (labour and delivery) hospitalizations and for postpartum readmissions. Risk
      factors for DVT/PE were identified using logistic regression. RESULTS: During the
      antepartum, peripartum, and postpartum periods, 5.4, 7.2, and 4.3 VTE cases per
      10,000 pregnancies, respectively were observed. The total incidence of DVT was
      12.1 per 10,000 pregnancies (0.26 deaths per 100,000), and the rate for PE was
      5.4 per 10,000 (0.96 deaths per 100,000). The strongest risk factors for DVT
      occurrence during the peripartum period were thrombophilia (adjusted odds ratio
      [aOR] 15.4; 95% CI 10.8-22.0), a past history of circulatory disease, and major
      puerperal infection, whereas those for PE were previous DVT (aOR 56.9; 95% CI
      40.9-79.1), heart disease (aOR 43.4, 95% CI 35.0-53.9), antiphospholipid
      syndrome, past history of circulatory disease, transfusion, and major puerperal
      infection. CONCLUSION: Cases of VTE and associated deaths occur most frequently
      during the peripartum period. Although mortality from pregnancy-associated VTE is
      low, maternal characteristics and other factors can be used to identify women at
      risk for VTE.

PMID- 19761635
TI  - Does routine induction of labour at 41 weeks really reduce the rate of caesarean
      section compared with expectant management?
AB  - OBJECTIVE: It is contended that routine induction of labour at 41 completed weeks
      of gestation reduces, or at least does not increase, a woman's chance of
      Caesarean section (CS), compared with expectant management. We wanted to know if
      this was true in our own hospital. METHODS: We performed a retrospective review
      of 1367 nulliparous women who had reached 41+0 weeks undelivered with a live,
      singleton, fetus with a cephalic presentation. The women comprised two non
      randomized contemporaneous cohorts: in one group, expectant management was
      planned, and in the second group the intention was to induce labour at 41 weeks.
      The primary outcome measure was the rate of CS in each group. RESULTS: Of 645
      women in whom expectant management was planned, 17.7% delivered by CS. Of 722
      women in whom induction of labour was planned, 21.3% delivered by CS (P = 0.09).
      Of the total of 907 women in whom expectant management was planned or who
      laboured spontaneously before planned induction could be carried out, 16.6%
      delivered by CS. Of 460 women in whom induction was planned and actually carried
      out, 25.4% delivered by CS (P = 0.001). CONCLUSION: The contention that routine
      induction of labour at 41 weeks reduces a woman's chance of delivery by Caesarean
      section was not supported by the findings of our study. Inducing labour may
      actually increase the nulliparous woman's risk of delivery by CS.

PMID- 19761636
TI  - Contraceptive use among Canadian women of reproductive age: results of a national
      survey.
AB  - OBJECTIVE: Past studies indicate that despite a wide range of contraceptive
      options, Canadian women tend to use a narrow selection of contraceptive methods.
      New contraceptive methods have recently been introduced in Canada. The objective
      of this research is to characterize Canadian women's current contraceptive
      choices and adherence to contraceptive regimens. METHODS: A national cross
      sectional survey was conducted in November 2006. A standardized, confidential,
      Internet questionnaire was administered to female members of a previously
      recruited national market research panel. Percentages of current contraceptive
      use and consistency of use were calculated by age group, marital status, and
      province and were weighted according to age and region. Chi-square test was used
      to detect within-group differences for consistency of contraceptive use, oral
      contraceptive (OC) use, and condom use. Multivariate logistic regression analyses
      predicting consistent contraception use, OC use, and condom use were performed.
      RESULTS: Of 5597 survey respondents, 3253 were eligible for data analysis. Of
      these women, 2751 had had vaginal intercourse in the previous six months, were
      not trying to conceive, and reported whether they or their partner had used
      contraception. Of these 2751 women, 410 (14.9%) never used contraception. Among
      contraception users, the most frequently used methods of contraception were
      condoms (54.3%), OCs (43.7%), and withdrawal (11.6%). Newer contraceptive methods
      were used by less than 4%. Choice of contraceptive method varied by age. Only
      65.2% of respondents who were sexually active and not trying to conceive "always
      used" contraception. Multivariate logistic regression analyses found
      significantly higher odds of no contraception use in women over 40 years of age,
      without higher education, living in PEI or Newfoundland, married or living common
      law, or having annual household incomes under $100,000. CONCLUSION: Despite many
      contraceptive options, Canadian women continue to use a narrow range of
      contraceptive methods and to use contraception inconsistently. Consistent
      contraceptive use is influenced by a number of independent social variables.
      Future public health initiatives should focus on raising awareness of
      contraception options, increased access to a variety of contraceptive methods,
      and assisting with contraceptive adherence.

PMID- 19761637
TI  - Laparoscopic peritoneal entry preferences among Canadian gynaecologists.
AB  - OBJECTIVES: To understand current laparoscopic entry practices among Canadian
      gynaecologists and to raise awareness of patient safety in accordance with the
      Society of Obstetricians and Gynaecologists of Canada clinical practice
      guideline, "Laparoscopic Entry: A Review of Techniques, Technologies, and
      Complications," published in May 2007. METHODS: A national survey was designed to
      determine different laparoscopic entry methods used by practising gynaecologists,
      to determine entry locations, and to gather information about mishaps. The survey
      was translated into French for francophone practitioners. In total, the survey
      was forwarded to 590 SOGC members. RESULTS: Of 269 responses (a 45.6% response
      rate), 224 responses were from obstetrician-gynaecologists who identified
      themselves as currently practising laparoscopy. Seventy-five percent of these
      respondents reported that they had read the SOGC laparoscopic entry guideline.
      There was no significant difference in practice patterns when comparing
      geographic practice location, gender, and number of years in practice. For
      laparoscopy in an unscarred abdomen, the most common entry method is Veress
      needle insufflation with closed trocar entry (78.9%). When adhesions are
      suspected, only 25.4% utilize the left upper quadrant. Of respondents, 28.7% use
      an insufflation pressure of 20-25 mm Hg. CONCLUSIONS: Our survey had a
      significant response rate and was able to delineate current laparoscopic entry
      practice patterns of gynaecologists, which were consistent across Canada. Despite
      72.9% of respondents reporting familiarity with the recent SOGC clinical practice
      guideline, it appears that clinical practice does not necessarily coincide with
      current recommendations. These variances in gynaecological practice emphasize the
      need for further educational initiatives to ensure that the evidence from
      research is used to make clinical practice safer.

PMID- 19761638
TI  - Uterine rupture resulting from the pressure of an intrauterine balloon.
AB  - BACKGROUND: Asherman's syndrome, or intrauterine synechiae, is characterized by
      partial or complete obliteration of the uterine cavity and/or the cervical canal.
      In order to preserve the integrity of the uterine cavity after correction,
      placement of an intrauterine Foley catheter with the balloon inflated is
      routinely performed. CASE: We report a case of uterine rupture and
      intraperitoneal bleeding presumably related to the pressure of the intrauterine
      balloon following hysteroscopic lysis of adhesions. CONCLUSION: We conclude that
      uterine rupture can occur because of intrauterine expansion of a Foley balloon
      after hysteroscopic treatment of intrauterine synechiae.

PMID- 19761639
TI  - Congenital urethrovaginal fistula with imperforate hymen: a first case report.
AB  - BACKGROUND: Congenital urethrovaginal fistulas are rare, and all five reported
      cases have been associated with urogenital abnormalities. We describe a case of
      congenital urethrovaginal fistula with an imperforate hymen and no other
      urogenital abnormalities. CASE: A 25-year-old female sought medical advice
      regarding cyclical hematuria, dyspareunia, and infertility of four years'
      duration. Investigations disclosed a urethrovaginal fistula with an imperforate
      hymen. The patient was successfully treated with excision of the hymen and
      closure of the urethrovaginal fistula. CONCLUSION: In this instance, the
      diagnosis of congenital urethrovaginal fistula was delayed until adulthood
      because the presence of urinary incontinence, the usual presentation of a
      urethrovaginal fistula, was concealed by the imperforate hymen. We could find no
      previously reported case of urethrovaginal fistula with imperforate hymen.

PMID- 19761640
TI  - The effectiveness of Proctofoam-HC for treatment of hemorrhoids in late
      pregnancy.
AB  - OBJECTIVE: Currently no topical anti-hemorrhoidal agents have been studied for
      effectiveness in pregnancy. This study evaluated the effectiveness of Proctofoam
      HC used during the last trimester of pregnancy. METHODS: In this prospective,
      open-label, observational study, pregnant women prescribed Proctofoam-HC were
      asked to complete two telephone interview questionnaires. RESULTS: A total of 88
      women completed the study. All hemorrhoidal symptoms, including pain, pruritus,
      swelling, itching, decreased significantly (P < 0.001) and overall well-being
      improved. The improvement was clinically very significant after correction for
      potential placebo effect. CONCLUSIONS: Proctofoam-HC appears to provide effective
      treatment of hemorrhoids in late pregnancy.

PMID- 19761641
TI  - Some thoughts on the SOGC Health Human Resources Project.

PMID- 19761642
TI  - Policy Statement on Midwifery.
AB  - This policy statement was developed by the Executive of the Society of
      Obstetricians and Gynaecologists of Canada in collaboration with the Associate
      Midwife Advisory Committee and approved by the Council of the Society of
      Obstetricians and Gynaecologists of Canada.

PMID- 19761644
TI  - Conflict of Interest.
AB  - This policy statement was developed by the International Women's Health Committee
      and approved by the Executive and Council of the Society of Obstetricians and
      Gynaecologists of Canada (SOGC).

PMID- 19761646
TI  - The role of obstetrician-gynaecologists in Canada.
AB  - This policy statement was prepared by the Executive and approved by the Council
      of the Society of Obstetricians and Gynaecologists of Canada.

PMID- 19761648
TI  - Initial evaluation and referral guidelines for management of pelvic/ovarian
      masses.
AB  - OBJECTIVES: To optimize the management of adnexal masses and to assist primary
      care physicians and gynaecologists determine which patients presenting with an
      ovarian mass with a significant risk of malignancy should be considered for
      gynaecologic oncology referral and management. OPTIONS: Laparoscopic evaluation,
      comprehensive surgical staging for early ovarian cancer, or tumour debulking for
      advanced stage ovarian cancer. OUTCOMES: To optimize conservative versus
      operative management of women with possible ovarian malignancy and to optimize
      the involvement of gynaecologic oncologists in planning and delivery of
      treatment. EVIDENCE: Published literature was retrieved through searches of
      PubMed or MEDLINE, CINAHL, and the Cochrane Library, using appropriate controlled
      vocabulary and key words. Results were restricted to systematic reviews,
      randomized control trials/controlled clinical trials, and observational studies.
      Grey (unpublished) literature was identified by searching the web sites of health
      technology assessment and health technology assessment-related agencies, clinical
      practice guideline collections, clinical trial registries, and national and
      international medical specialty societies. RECOMMENDATIONS: 1. Primary care
      physicians and gynaecologists should always consider the possibility of an
      underlying ovarian cancer in patients in any age group who present with an
      adnexal or ovarian mass. (II-2B) 2. Appropriate workup of a perimenopausal or
      postmenopausal woman presenting with an adnexal mass should include evaluation of
      symptoms and signs suggestive of malignancy, such as persistent pelvic/abdominal
      pain, urinary urgency/frequency, increased abdominal size/bloating, and
      difficulty eating. In addition, CA125 measurement should be considered. (II-2B)
      3. Transvaginal or transabdominal ultrasound examination is recommended as part
      of the initial workup of a complex adnexal/ovarian mass. (II-2B) 4. Ultrasound
      reports should be standardized to include size and unilateral/bilateral location
      of the adnexal mass and its possible origin, thickness of septations, presence of
      excrescences and internal solid components, vascular flow distribution pattern,
      and presence or absence of ascites. This information is essential for calculating
      the risk of malignancy index II score to identify pelvic mass with high malignant
      potential. (IIIC) 5. Patients deemed to have a high risk of an underlying
      malignancy should be reviewed in consultation with a gynaecologic oncologist for
      assessment and optimal surgical management. (II-2B).

PMID- 19761650
TI  - Understanding the role of nutrition in the brain and behavioral development of
      toddlers and preschool children: identifying and addressing methodological
      barriers.
AB  - The preschool years (i.e. 1-5 years of age) is a time of rapid and dramatic
      postnatal brain development (i.e. neural plasticity), and of fundamental
      acquisition of cognitive development (i.e. working memory, attention and
      inhibitory control). Also, it is a time of transition from a direct maternal
      mediation/selection of diet-based nutrition to food selection that is more based
      on self-selection and self-gratification. However, there have been fewer
      published studies in preschool children than in infants or school-aged children
      that examined the role of nutrition in brain/mental development (125 studies
      versus 232 and 303 studies, respectively during the last 28 years). This may
      arise because of age-related variability, in terms of individual differences in
      temperament, linguistic ability, and patterns of neural activity that may affect
      assessment of neural and cognitive development in pre-school children. In this
      review, we suggest several approaches for assessing brain function in children
      that can be refined. It would be desirable if the discipline developed some
      common elements to be included in future studies of diet and brain function, with
      the idea that they would complement more targeted measures based on time of
      exposure and understanding of data from animal models. Underlining this approach
      is the concept of 'window of sensitivity' during which nutrients may affect
      postnatal neural development: investigators and expert panels need to look
      specifically for region-specific changes and do so with understanding of the
      likely time window during which the nutrient was, or was not available.

PMID- 19761652
TI  - Normalization of zinc intake enhances neurological retrieval of patients
      suffering from ischemic strokes.
AB  - INTRODUCTION: The objective of this study was to investigate whether zinc (Zn2+)
      supplementation could contribute to neurological retrieval of patients suffering
      from strokes and low Zn2+ intake. PATIENTS AND METHODS: Twenty-six patients with
      subacute stroke, having adequate daily energy (> or = 24 kcal/kg/day) and protein
      (> or = 0.8 g/kg/day) intake (EPI) and Zn2+ ingestion lower than two-thirds of
      the recommended allowance of 10 mg/day, were randomly allocated either to a
      control group (n = 13) or Zn2+ group (n = 13) where Zn2+ supplementation
      consisted of 10 mg Zn2+/day. Neurological gravity was tested with the NIH stroke
      scale (NIHSS) at patient admission and after 30 days of protocol commencement.
      RESULTS: At day 30, the improvement in NIHSS was higher in the zinc group than in
      the placebo (-4.7 +/- 1.3 points versus -3.3 +/- 1.1 points; P < 0.02). NIHSS and
      Zn2+ intake were negatively correlated (r = -0.46; P < 0.02). CONCLUSION: The
      normalization of Zn2+ intake in stroke patients with low mineral intake may
      enhance neurological recovery.

PMID- 19761651
TI  - Antioxidants and cognitive training interact to affect oxidative stress and
      memory in APP/PSEN1 mice.
AB  - The present study investigated the relationships among oxidative stress, beta
      amyloid and cognitive abilities in the APP/PSEN1 double-transgenic mouse model of
      Alzheimer's disease. In two experiments, long-term dietary supplements were given
      to aged APP/PSEN1 mice containing vitamin C alone (1 g/kg diet; Experiment 1) or
      in combination with a high (750 IU/kg diet, Experiments 1 and 2) or lower (400
      IU/kg diet, Experiment 2) dose of vitamin E. Oxidative stress, measured by F(4)
      neuroprostanes or malondialdehyde, was elevated in cortex of control-fed
      APP/PSEN1 mice and reduced to wild-type levels by vitamin supplementation. High
      dose vitamin E with C was less effective at reducing oxidative stress than
      vitamin C alone or the low vitamin E+C diet combination. The high-dose
      combination also impaired water maze performance in mice of both genotypes. In
      Experiment 2, the lower vitamin E+C treatment attenuated spatial memory deficits
      in APP/PSEN1 mice and improved performance in wild-type mice in the water maze.
      Amyloid deposition was not reduced by antioxidant supplementation in either
      experiment.

PMID- 19761653
TI  - Folate stimulates ERK1/2 phosphorylation and cell proliferation in fetal neural
      stem cells.
AB  - Cellular events for neural progenitor cells, such as proliferation and
      differentiation, are regulated by multiple intrinsic and extrinsic cell signals.
      Folate plays central roles in central nervous system development, so folate, as
      an extrinsic signal, may affect neural stem cell (NSC) proliferation and
      differentiation. In this study, we have investigated the effect of folate on
      extracellular signal-regulated kinase (ERK1/2) phosphorylation, cell
      proliferation and apoptosis in fetal NSCs. The results showed that treatment of
      neurospheres with folate increased ERK1/2 phosphorylation and cell proliferation
      in a concentration-dependent manner. Folate also decreased the percentage of
      apoptotic cells. All of these effects of folate were prevented by a selective
      inhibitor (U0126) of mitogen-activated/ERK kinase 1/2. In conclusion, fetal NSCs
      respond to folate with ERKl/2 phosphorylation, cell proliferation and decreased
      apoptosis. This mechanism may mediate the regulation by folate of neurogenesis in
      the central nervous system.

PMID- 19761654
TI  - Constant light induces alterations in melatonin levels, food intake, feed
      efficiency, visceral adiposity, and circadian rhythms in rats.
AB  - Melatonin levels, metabolic parameters, circadian rhythm activity patterns, and
      behavior were observed in rats subjected to a 12-h/12-h light/dark cycle (LD)
      compared to animals exposed to continuous dark (DD) or continuous light (LL). LD
      and DD animals were similar in melatonin levels, food intake, relative food
      intake, feed efficiency, water intake, circadian activity levels, and behavior.
      LL animals had lower melatonin levels in the subjective dark compared to LD and
      DD animals. Food intake, relative food intake, and water intake values were lower
      and feed efficiency was more positive in LL animals compared to LD and DD
      animals. In addition, LL animals exhibited greater visceral adiposity than the
      other two groups. The circadian rhythmicity of activity became free-running in LL
      animals and there was a decrease in overall activity. Notable behavioral changes
      in LL animals were an increase in irritability and excitability. Results indicate
      that a decrease in melatonin levels and concomitant changes in metabolism,
      circadian rhythms, and behavior are consequences of exposure to constant light.

PMID- 19761655
TI  - Comparison of two self-rating scales to detect depression: HADS and PHQ-9.
AB  - BACKGROUND: More than half of patients with depression go undetected. Self-rating
      scales can be useful in screening for depression, and measuring severity and
      treatment outcome. AIM: This study compares the Hospital Anxiety and Depression
      Scale (HADS) and the Patient Health Questionnaire (PHQ-9) with regard to their
      psychometric properties, and investigates their agreement at different cut-off
      scores. METHOD: Swedish primary care patients and psychiatric outpatients (n =
      737) who reported symptoms of depression completed the self-rating scales. Data
      were collected from 2006 to 2007. Analyses with respect to internal consistency,
      factor analysis, and agreement (Cohen's kappa) at recommended cut-offs were
      performed. RESULTS: Both scales had high internal consistency (alpha = 0.9) and
      stable factor structures. Using severity cut-offs, the PHQ-9 (> or =5) diagnosed
      about 30% more patients than the HADS depression subscale (HADS-D; > or =8). They
      recognised the same prevalence of mild and moderate depression, but differed in
      relation to severe depression. When comparing recommended screening cut-offs,
      HADS-D > or =11 (33.5% of participants) and PHQ-9 > or =10 (65.9%) agreement was
      low (kappa = 0.35). Using the lower recommended cut-off in the HADS-D (> or =8),
      agreement with PHQ-9 > or =10 was moderate (kappa = 0.52). The highest agreement
      (kappa = 0.56) was found comparing HADS-D > or =8 with PHQ-9 > or =12. This also
      equalised the prevalence of depression found by the scales. CONCLUSION: The HADS
      and PHQ-9 are both quick and reliable. The HADS has the advantage of evaluating
      both depression and anxiety, and the PHQ-9 of being strictly based upon the
      Diagnostic and Statistical Manual of Mental Disorders. The agreement between the
      scales at the best suitable cut-off is moderate, although the identified
      prevalence was similar. This indicates that the scales do not fully identify the
      same cases. This difference needs to be further explored.

PMID- 19761656
TI  - Decisions about referrals for psychological therapies: a matched-patient
      qualitative study.
AB  - BACKGROUND: Psychological therapies are effective treatments for common mental
      health problems, but access is limited. GPs face difficult decisions as to whom
      to refer, but little is known about this decision-making process. AIM: To explore
      GPs' accounts of decisions to refer, or not refer, patients for psychological
      therapy. DESIGN OF STUDY: A qualitative study, using a matched-patient procedure.
      SETTING: General practices in two inner London boroughs. METHOD: In semi
      structured interviews, GPs were asked to compare and contrast five matched
      patient pairs, consisting of patients who had been referred for psychological
      therapy paired with patients not referred. The interviews were analysed using a
      general thematic analysis. RESULTS: Fourteen GPs discussed 130 matched patients
      (65 patient pairs). Three main factors distinguished GPs' accounts of the
      patients they referred compared with the matched patients they did not refer.
      These factors were: patient initiative in requesting or showing interest in
      referral; estimated capacity of the patient to benefit from psychological
      therapy; and the GP's own capacity to help the patient in terms of skills,
      expertise, and time. CONCLUSION: GPs gave accounts of themselves acting as
      rational decision makers, judging how effective they thought a referral would be
      based on a patient's clinical presentation and motivation, compared with the GPs'
      own ability to help.

PMID- 19761657
TI  - Commentary: GPs' views on their handling of depression.

PMID- 19761658
TI  - 'A coal face option': GPs' perspectives on the rise in antidepressant
      prescribing.
AB  - BACKGROUND: Levels of antidepressant prescribing have dramatically increased in
      Western countries in the last two decades. AIM: To explore GPs' views about, and
      explanations for, the increase in antidepressant prescribing in Scotland between
      1995 and 2004. DESIGN: Qualitative, interview study. SETTING: General practices,
      Scotland. PARTICIPANTS: GPs in 30 practices (n = 63) purposively selected to
      reflect a range of practice characteristics and levels of antidepressant
      prescribing. METHOD: Interviews with GPs were taped and transcribed. Analysis
      followed a Framework Approach. RESULTS: GPs offered a range of explanations for
      the rise in antidepressant prescribing in Scotland. Few doctors thought that the
      incidence of depression had increased, and many questioned the appropriateness of
      current levels of prescribing. A number of related factors were considered to
      have contributed to the increase. These included: the success of campaigns to
      raise awareness of depression; a willingness among patients to seek help; and the
      perceived safety of selective serotonin reuptake inhibitors, making it easier for
      GPs to manage depression in primary care. Many GPs believed that unhappiness,
      exacerbated by social deprivation and the breakdown of traditional social
      structures, was being 'medicalised' inappropriately. CONCLUSION: Most
      antidepressant prescriptions in Scotland are issued by GPs, and current policy
      aims to reduce levels of prescribing. To meet this aim, GPs' prescribing
      behaviour needs to change. The findings suggest that GPs see themselves as
      responders to, rather than facilitators of, change and this has obvious
      implications for initiatives to reduce prescribing.

PMID- 19761659
TI  - GPs' role in the detection of psychological problems of young people: a
      population-based study.
AB  - BACKGROUND: Among young people, about one in three females and one in five males
      report experiencing emotional distress but 65-95% of them do not receive help
      from health professionals. AIM: To assess the differences among young people who
      seek help and those who do not seek help for their psychological problems,
      considering the frequency of consultations to their GP and their social
      resources. DESIGN OF STUDY: School survey. SETTING: Post-mandatory school.
      METHOD: Among a Swiss national representative sample of 7429 students and
      apprentices (45.6% females) aged 16-20 years, 1931 young people reported needing
      help for a problem of depression/sadness (26%) and were included in the study.
      They were divided into those who sought help (n = 256) and those who did not (n =
      1675), and differences between them were assessed. RESULTS: Only 13% of young
      people needing help for psychological problems consulted for that reason and this
      rate was positively associated with the frequency of consultations to the GP.
      However, 80% of young people who did not consult for psychological problems
      visited their GP at least once during the previous year. Being older or a
      student, having a higher depression score, or a history of suicide attempt were
      linked with a higher rate of help seeking. Moreover, confiding in adults
      positively influenced the rate of help seeking. CONCLUSION: The large majority of
      young people reporting psychological problems do not seek help, although they
      regularly consult their GP. While young people have difficulties in tackling
      issues about mental health, GPs could improve the situation by systematically
      inquiring about this issue.

PMID- 19761661
TI  - Reasons to be cheerful? Reflections on GPs' responses to depression.

PMID- 19761662
TI  - To disclose or not to disclose psychological problems to GPs.

PMID- 19761663
TI  - Improving access to psychological therapies: implications for mental health care
      in general practice.

PMID- 19761664
TI  - Knowing patients' preferences for place of death: how possible or desirable?

PMID- 19761665
TI  - Appropriateness of antidepressant prescribing: an observational study in a
      Scottish primary-care setting.
AB  - BACKGROUND: Since the 1990s, Scottish community-based antidepressant prescribing
      has increased substantially. AIM: To assess whether GPs prescribe antidepressants
      appropriately. DESIGN OF STUDY: Observational study of adults (aged >/=16 years)
      screened with the Hospital Anxiety and Depression Scale (HADS) attending a GP.
      SETTING: Four practices in Grampian, Scotland. METHOD: Patients (n = 898)
      completed the HADS, and GPs independently estimated depression status. Notes were
      scrutinised for evidence of antidepressant use, and the appropriateness of
      prescribing was assessed. RESULTS: A total of 237 (26%) participants had HADS
      scores indicating 'possible' (15%) or 'probable' (11%) depression. The proportion
      of participants rated as depressed by their GP differed significantly by HADS
      depression subscale scores. Odds ratio for 'possible' versus 'no' depression was
      3.54 (95% confidence interval [CI] = 2.17 to 5.76, P<0.001); and for 'probable'
      versus 'possible' depression was 3.59 (95% CI = 2.06 to 6.26, P<0.001).
      Similarly, the proportion of participants receiving antidepressants differed
      significantly by HADS score. Odds ratio for 'possible' versus 'no' depression was
      2.79 (95% CI = 1.70 to 4.58, P<0.001); and for 'probable' versus 'possible' was
      2.12 (95% CI = 1.21 to 3.70, P = 0.009). In 101 participants with 'probable'
      depression, GPs recognised 53 (52%) participants as having a clinically
      significant depression. Inappropriate initiation of antidepressant treatment
      occurred very infrequently. Prescribing to participants who were not symptomatic
      was accounted for by the treatment of pain, anxiety, or relapse prevention, and
      for ongoing treatment of previously identified depression. CONCLUSION: There was
      little evidence of prescribing without relevant indication. Around half of
      patients with significant symptoms were not identified by their GP as suffering
      from a depressive disorder: this varied inversely with severity ratings. Rather
      than prescribing indiscriminately (as has been widely assumed), it is likely that
      GPs are initiating antidepressant treatment conservatively.

PMID- 19761666
TI  - Associations between home death and GP involvement in palliative cancer care.
AB  - BACKGROUND: Most cancer patients die at institutions despite their wish for home
      death. GP-related factors may be crucial in attaining home death. AIM: To
      describe cancer patients in palliative care at home and examine associations
      between home death and GP involvement in the palliative pathway. DESIGN OF STUDY:
      Population-based, combined register and questionnaire study. SETTING: Aarhus
      County, Denmark. METHOD: Patient-specific questionnaires were sent to GPs of 599
      cancer patients who died during a 9-month period in 2006. The 333 cases that were
      included comprised information on sociodemography and GP-related issues; for
      example knowledge of the patient, unplanned home visits, GPs providing their
      private phone number, and contact with relatives. Register data were collected on
      patients' age, sex, cancer diagnosis, place of death, and number of GP home
      visits. Associations with home death were analysed in a multivariable regression
      model with prevalence ratios (PR) as a measure of association. RESULTS: There was
      a strong association between facilitating home death and GPs making home visits
      (PR = 4.3, 95% confidence interval [CI] = 1.2 to 14.9) and involvement of
      community nurses (PR = 1.4, 95% CI = 1.0 to 1.9). No other GP-related variables
      were statistically significantly associated with home death. CONCLUSION: Active
      involvement of GPs providing home visits and the use of home nurses were
      independently associated with a higher likelihood of facilitating home death for
      cancer patients. The primary care team may facilitate home death, accommodating
      patients' wishes. Future research should examine the precise mechanisms of their
      involvement.

PMID- 19761667
TI  - Practice-based research.

PMID- 19761669
TI  - Future of general practice.

PMID- 19761671
TI  - Sickness certification.

PMID- 19761673
TI  - NICE guidelines on complementary/alternative medicine: more consistency and
      rigour are needed.

PMID- 19761675
TI  - Family medicine in Japan.

PMID- 19761679
TI  - Cognitive behavioural therapy and reminiscence techniques for the treatment of
      depression in the elderly: a systematic review.
AB  - Psychotherapy, including cognitive behavioural therapy (CBT), reminiscence and
      general psychotherapy (GPT), is viewed as effective treatment for depression, but
      its efficacy in older people is not well defined. This systematic review included
      14 randomized controlled trials that assessed the efficacy of psychotherapy for
      treating depression in elderly people (> or = 55 years). The results of this meta
      analysis showed that, compared with placebo, psychotherapy was more effective in
      reducing depression scores (standardized mean difference -0.92; 95% confidence
      interval -1.21, -0.36). Subgroup analysis showed that CBT, reminiscence and GPT
      were all more effective than placebo; psychotherapy as an adjunct to
      antidepressant medication did not increase effectiveness. There was no
      significant difference between CBT and reminiscence in improving depression. A
      higher drop-out rate was observed in studies that did not include psychotherapy
      versus those that did, although this difference was not statistically
      significant. Thus, various general formats of psychotherapy are effective for
      treating depression in older people, although psychotherapy does not
      significantly increase the effectiveness of anti-depressant medication.

PMID- 19761680
TI  - Classification and prediction of outcome in traumatic brain injury based on
      computed tomographic imaging.
AB  - Traumatic brain injury (TBI) is a common and potentially devastating problem. The
      classification of TBI is necessary for accurate diagnosis and the prediction of
      outcomes. The increased use of early sedation, intubation and ventilation in more
      severely injured patients has decreased the value of the Glasgow Coma Scale for
      the purposes of classification. An alternative is the classification of TBI
      according to morphological criteria based on computed tomography (CT)
      investigations. This article reviews the current classification and prediction of
      outcomes in TBI based on CT imaging. Classifications based on the presence or
      absence of intracranial local lesions, diffuse injury, signs of subarachnoid or
      intra-ventricular haemorrhage and fractures or foreign bodies are considered, and
      their predictive value is discussed. Future studies should address the
      complicated issue of how optimally to combine CT characteristics for prognostic
      purposes and how to improve on currently used CT classifications to predict
      outcomes more accurately.

PMID- 19761681
TI  - Drugs with blocking effects on the renin-angiotensin-aldosterone system do not
      improve endothelial dysfunction long-term in hypertensive patients.
AB  - In essential hypertension, endothelial dysfunction has been documented many times
      and correlates with prognosis. The influence of the renin-angiotensin-aldosterone
      system (RAAS) on endothelial dysfunction has also been studied. The present study
      investigated the duration of the effects of RAAS-blocking drugs on endothelial
      function in 44 consecutive, never-treated, outpatients with mild to moderate
      hypertension. Patients (11 per group) received an angiotensin receptor blocker
      (ARB; irbesartan 300 mg/day or valsartan 160 mg/day) or an angiotensin-converting
      enzyme inhibitor (ACEi; fosinopril 10 mg/day or quinapril 20 mg/day). If target
      blood pressure (< 140/90 mmHg) was not achieved, 12.5 mg/day hydrochlorothiazide
      was added. Endothelial function, assessed by measuring brachial artery diameter,
      did not change significantly after 6 weeks, 1 year or 3 years of treatment in any
      group. Across all groups, endothelium-dependent and -independent vasodilation
      increased significantly after 6 weeks but, after 1 year, decreased below baseline
      and was at a similar level after 3 years; groups did not differ significantly.
      Both ACEi and ARB had similar effects on endothelial function; improvement
      occurred at the start of treatment but was not maintained. Endothelial
      dysfunction may be a resistant or irreversible feature of hypertension, requiring
      high doses of antihypertensive drugs and above-average patient compliance.

PMID- 19761682
TI  - Effects of endothelial nitric oxide synthase, interleukin-6 gene polymorphisms
      and asymmetric dimethylarginine levels on risk factors and lesion sites in
      peripheral artery disease.
AB  - This study investigated risk factors for atherosclerosis and their relationship
      with lesion sites. Patients (n = 160) with peripheral artery disease (PAD)
      completed a questionnaire regarding risk factors for PAD. Endothelial nitric
      oxide synthase (eNOS) and interleukin (IL)-6 gene polymorphisms and asymmetric
      dimethylarginine (ADMA) levels were measured. Patients with coronary artery
      disease had significantly higher ratios of eNOS T/C and C/C genotypes, which
      include the C allele, than the T/T genotype. The IL-6 gene polymorphism
      distribution ratios for patients with over four risk factors were significantly
      different compared with other patients, with a higher rate of the C/C genotype.
      ADMA levels did not show any significant relationship to risk factors or
      polymorphism. Levels were, however, slightly higher in femoral lesion sites. The
      results support a model in which the C/C genotype of eNOS and IL-6 gene
      polymorphisms promote PAD development. The eNOS C/C genotype may have an
      independent effect, whereas the effects of the IL-6 C/C genotype are seen in
      conjunction with other risk factors.

PMID- 19761683
TI  - Effects of thiopental on endothelium-dependent relaxation in porcine coronary
      arteries.
AB  - This study investigated the effects of thiopental on endothelium-dependent
      relaxation (EDR), and especially the effects on nitric oxide- and prostacyclin
      independent EDR. Fresh porcine coronary artery rings (4 mm long), were
      consecutively tested with and without 20 microg/ml thiopental in Krebs-Henseleit
      solution. Indomethacin (10 micromol/l) was used in all experiments to eliminate
      prostacyclin effects. Prostaglandin F(2alpha) (10 micromol/l) was used to induce
      contractions and bradykinin (10(-10) - 10(-5) M) was used to induce EDR.
      Experiments were also carried out using 300 micromol/l N-nitro-L-arginine to
      block nitric oxide production and to assess the influence of thiopental on nitric
      oxide- and prostacyclin-independent EDR. Thiopental induced statistically
      significant increases in EDR at concentrations of 10(-6) - 10(-5) M bradykinin.
      Following nitric oxide production block, thiopental significantly reduced the
      relaxation response at concentrations of 10(-8) - 10(-5) M bradykinin. At a
      clinically relevant concentration of 20 microg/ml thiopental, a significant
      increase in EDR and a significant reduction in nitric oxide- and prostacyclin
      independent relaxation was observed in porcine epicardial coronary arteries.

PMID- 19761684
TI  - Effects of imatinib mesylate on renin-angiotensin system (RAS) activity during
      the clinical course of chronic myeloid leukaemia.
AB  - The renin-angiotensin system (RAS) is involved in cell growth, proliferation and
      differentiation in bone marrow in an autocrine-paracrine manner, and it modulates
      normal and neoplastic haematopoietic cell proliferation. This study aimed to
      assess expressions of the RAS components, renin, angiotensinogen and angiotensin
      converting enzyme (ACE), during imatinib mesylate treatment of patients with
      chronic myeloid leukaemia (CML). Expressions of RAS components were studied in
      patients with CML at the time of diagnosis (n = 83) and at 3, 6 and 12 months
      after diagnosis (n = 35) by quantitative real-time polymerase chain reaction. De
      novo CML patients had increased ACE, angiotensinogen and renin mRNA levels and
      these expression levels decreased following administration of imatinib. The RAS
      activities were significantly different among Sokal risk groups of CML,
      highlighting the altered biological activity of RAS in neoplastic disorders. The
      results of this study confirm that haematopoietic RAS affects neoplastic cell
      production, which may be altered via administration of tyrosine kinase inhibitors
      such as imatinib mesylate.

PMID- 19761685
TI  - Simvastatin reduces expression and activity of lipoprotein-associated
      phospholipase A(2) in the aorta of hypercholesterolaemic atherosclerotic rabbits.
AB  - Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) contributes to
      atherosclerotic plaque instability and subsequent sudden coronary death. Statins
      are associated with decreased stroke risk and may improve stability of
      atherosclerotic plaques. The present study investigated the effect of simvastatin
      on expression of Lp-PLA(2) levels in atherosclerotic plaques and on Lp-PLA(2)
      activity in atherosclerotic aortas. Rabbits were a fed chow (control group) or a
      high-cholesterol diet (atherosclerosis group) for 12 weeks. An additional group
      on the high-cholesterol diet received simvastatin (5 mg/kg per day) for the last
      4 weeks (simvastatin group). Lp-PLA(2) activity in plasma and atherosclerotic
      aortas was significantly higher in the atherosclerosis group than in the control
      group and, consistent with this, abundant Lp-PLA(2) protein was detected in
      plaques in the atherosclerosis group. Simvastatin significantly reduced Lp-PLA(2)
      activity in plasma and aorta tissue, and reduced Lp-PLA(2) protein level in
      atherosclerotic plaques. Whereas there was no significant difference in total
      atherosclerotic lesion area between simvastatin and atherosclerosis groups,
      simvastatin significantly reduced macrophage content, lipid retention and the
      intima/media ratio but increased the content of smooth muscle cells in
      atherosclerotic lesions. Thus, statin treatment markedly reduced Lp-PLA(2) in
      both plasma and atherosclerotic plaques. This was associated with attenuation of
      the local inflammatory response and improved plaque stability.

PMID- 19761686
TI  - Methylation in p14(ARF) is frequently observed in colorectal cancer with low
      level microsatellite instability.
AB  - Colorectal cancer (CRC) can be classified as high-level microsatellite
      instability (MSI-H), low-level MSI (MSI-L) and microsatellite stable (MSS)
      depending on levels of MSI. MSI-H CRC relies on a distinct molecular pathway due
      to the mismatch repair (MMR) deficiency and shows methylation in multiple gene
      promoters. The genetic pathway leading to MSI-L is unknown, although higher
      levels of promoter methylation are observed in this group compared with MSS CRCs.
      This study explored how promoter methylation affects MSI phenotype, by analysing
      the methylation status of eight CRC-related promoters, MSI phenotype and
      KRAS/BRAF mutations in a series of 234 CRCs. Promoter methylation of p14(ARF) was
      significantly related to MSI-L CRC with KRAS mutation. The MSI-H phenotype was
      related to methylation of MLH1 as expected, while the MSS phenotype was related
      to methylation of p16(INK4a) and O(6)-methylguanine-DNA methyltransferase,
      although this was not statistically significant. Thus, promoter methylation of
      p14(ARF) could be a significant alteration leading to CRC with MSI-L.

PMID- 19761687
TI  - Selective enrichment of hepatocellular cancer stem cells by chemotherapy.
AB  - This study investigated the enrichment of cancer stem cells (CSCs) in
      hepatocellular carcinoma (HCC) by chemotherapy. SMMC-7721 cells were inoculated
      into mice treated with 0, 2, 5 or 10 mg/kg cyclophosphamide (CTX). Tissue from
      the resulting tumours was re-inoculated into CTX-treated mice two more times,
      thus producing three generations of tumour cells for each dose of CTX. Chromosome
      and fluorescence-activated cell sorting analyses were performed to determine the
      purity of the enriched cells. Sphere culture, colony formation and proliferation
      assays demonstrated that the self-renewal potential, proliferative activity and
      clonogenicity of the enriched cells in vitro increased with increasing
      chemotherapy dose and generation. The ability of the enriched cells to produce
      xenograft tumours in mice was also dependent on chemotherapy dose and generation.
      In conclusion, subjecting HCC cells to chemotherapy in vivo enriched the samples
      for HCC CSCs in a dose- and generation-dependent manner.

PMID- 19761688
TI  - A comparison of proximal femoral nail antirotation and dynamic hip screw devices
      in trochanteric fractures.
AB  - This prospective, randomized study compared the functional outcome and
      complications associated with a proximal femoral nail antirotation (PFNA) device
      with those of a traditional extramedullary device, the dynamic hip screw (DHS),
      in patients with trochanteric fracture. A total of 121 patients were randomized
      to the PFNA group (n = 58) or the DHS group (n = 63). Perioperative information
      and complications were recorded, and assessments of functional outcome were made.
      The DHS group required a longer operative time and was associated with greater
      blood loss than the PFNA group. The re-operation rate was lower in the PFNA group
      compared with the DHS group, especially in patients with unstable fractures,
      although there was no statistically significant difference in the overall
      complication rate between the two groups. There were no significant differences
      in functional outcome between the PFNA and the DHS groups. In conclusion, the
      PFNA device is useful in the treatment of trochanteric fractures.

PMID- 19761689
TI  - Human papillomavirus type 16 exists in bacteria isolated from cervical cancer
      biopsies.
AB  - This study investigated the association between infectious microbes and
      persistent infection with human papillomavirus type 16 (HPV-16) in cervical
      cancer. Bacterial strains (identified as Enterococcus, Staphylococcus, Bacillus
      and Corynebacterium, based on their partial 16S rDNA sequence) were HPV-16
      positive from 12 out of 14 cervical cancer biopsies. Total DNA was isolated from
      the four bacterial strains, and HPV-16 genes and genome were detected using
      polymerase chain reaction (PCR) and Southern blotting. RNA transcripts for HPV-16
      E6 and L1 genes were detected in total bacterial RNA samples using reverse
      transcription-PCR, and HPV-16 L1 protein expression was detected in bacterial
      cells by Western blotting and immunocolloidal gold electron microscopy. The
      presence of virus particles in bacterial cells was demonstrated by transmission
      electron microscopy. The results suggest that bacteria carrying HPV-16 could
      provide a potential explanation for how infectious microbes contribute to the
      progression from HPV-16 infection to cervical cancer.

PMID- 19761690
TI  - Transplanted bone morphogenetic protein/poly(lactic-co-glycolic acid) delayed
      release microcysts combined with rat micromorselized bone and collagen for bone
      tissue engineering.
AB  - This study was designed to optimize the preparation of delayed-release microcysts
      containing bone morphogenetic protein 2 (BMP-2) combined with poly(lactic-co
      glycolic acid) (PLGA) and to investigate their osteogenic properties when
      combined with rat autologous micromorselized bone and collagen. Rat autologous
      micromorselized bone, collagen and BMP-2/PLGA delayed-release microcysts were
      implanted in various combinations into the rat gluteus maximus muscle sack model.
      The following post-operative measurements were made: general observations of the
      implant site, histological observations, osteogenesis measurements and alkaline
      phosphatase activity. Autologous micromorselized bone combined with collagen and
      BMP-2/PLGA delayed-release microcysts demonstrated significantly superior
      osteogenic properties than any of the other combinations of these three
      components. These findings suggest that micromorselized bone combined with
      collagen and BMP-2/PLGA delayed-release microcysts could reduce the quantity of
      BMP-2 and autologous bone required for these procedures, making their use
      feasible in human bone restoration.

PMID- 19761691
TI  - Discrimination between Sjogren's and non-Sjogren's sicca syndrome by
      sialoscintigraphy and antibodies against alpha-fodrin and Ro/La autoantigens.
AB  - Both Sjogren's syndrome (SS) and non-Sjogren's syndrome (NSS) can present with
      the sicca symptoms of dry eyes and a dry mouth but they are distinct pathological
      entities that require diagnostic discrimination. This study included 82 sicca
      syndrome patients and examined the ability of sialoscintigraphy and antibodies
      against the autoantigens alpha-fodrin, Ro and La to discriminate between SS and
      NSS. A total of 30.8% of SS patients compared with 58.8% of NSS patients were
      alpha-fodrin positive. The prevalence of Ro positivity was 69.4% for SS patients
      compared with 0% for NSS patients. The prevalence of La positivity was 52.4% for
      SS compared with 0% for NSS patients. Sialoscintigraphy showed that more NSS
      patients had grade III salivary gland impairment compared with SS patients (64.7%
      versus 19.4%). These data suggest that using sialoscintigraphy in combination
      with measuring the levels of serum alpha-fodrin, Ro and La might be useful for SS
      and NSS discrimination.

PMID- 19761692
TI  - Insulin with chondroitinase ABC treats the rat model of acute spinal cord injury.
AB  - Traumatic brain injury is often associated with acute spinal cord injury (ASCI).
      Insulin and chondroitinase ABC (ChABC) are both therapeutically effective, but
      the combined therapeutic effect of insulin and ChABC is still not clear. A
      combination of insulin and ChABC were used to treat a rat model of ASCI. This
      combination therapy prevented neuronal cell death by improving motor function,
      increasing cell growth and inhibiting cell apoptosis in ASCI rats. Expression of
      growth-associated protein 43, a marker of axonal re-growth, increased after
      combined treatment with insulin and ChABC. These results may provide a basis for
      a future method of treating ASCI.

PMID- 19761693
TI  - Vision-related quality of life and emotional impact in children with strabismus:
      a prospective study.
AB  - The potential impact of the surgical correction of strabismus on vision-related
      quality of life (VRQOL) and the symptoms of anxiety and depression in children
      with strabismus remain unclear. The present study included 60 children with
      strabismus: 30 with heterophoria and 30 with heterotropia. A healthy age- and
      gender-matched control group (n = 60) was also recruited. The psychological
      instruments that were used were the short-form 25-item National Eye Institute
      Visual Functioning Questionnaire (NEI-VFQ-25) and the Hospital Anxiety and
      Depression Scale (HADS). The results demonstrated that eight of the 12 NEI-VFQ-25
      subscales were significantly impaired in children with strabismus compared with
      matched controls. Compared with pre-operative values, significant improvements
      were noted after surgery in the NEI-VFQ-25 summary score, and the anxiety and
      depression scores. This study demonstrated that the NEI-VFQ-25 instrument can be
      used in strabismus children and that surgical interventions can improve VRQOL,
      anxiety and depression in strabismus patients.

PMID- 19761694
TI  - Synergistic effect of a novel focal hyperthermia on the efficacy of rifampin in
      staphylococcal experimental foreign-body infection.
AB  - This study was designed to evaluate the efficacy of focal hyperthermia and
      rifampin in vitro and in vivo using a rabbit model of foreign-body infection by
      methicillin-resistant Staphylococcus aureus (MRSA). In vitro studies demonstrated
      bacterial re-growth and development of rifampin resistance after 24 h with
      rifampin alone, which was prevented under hyperthermic conditions. For the in
      vivo studies, rifampin was administered intraperitoneally every 12 h for 7 days
      to rabbits with MRSA-containing cages implanted into their flanks. When combined
      with hyperthermia at 39 degrees C, 41 degrees C and 43 degrees C, rifampin
      significantly reduced in-cage bacterial counts by > 3.0 log(10) colony forming
      units/ml compared with rifampin alone. Eradication of cage-associated infection
      was achieved more effectively when rifampin was combined with hyperthermia, with
      cure rates of 70-95% on day 10. Focal hyperthermia combined with rifampin
      prevented the emergence of rifampin resistance and maintained rifampin efficacy.
      These findings might have implications for orthopaedic surgery.

PMID- 19761695
TI  - Clinical significance of telomerase activity in gastric carcinoma and peritoneal
      dissemination.
AB  - Telomerase activity is responsible for telomere maintenance and is believed to be
      crucial in most cancer cells, but its significance in gastric cancer remains
      unknown. This observational study investigated whether there is a relationship
      between telomerase activity and the development of gastric cancer, and between
      telomerase activity and peritoneal dissemination. Telomerase activity was
      measured in primary gastric cancers and in peritoneal washings from the same
      patients, and findings were compared with those of conventional cytology and an
      immunoassay for cancer antigen 125 (CA125). Positive cytological examination and
      telomerase activity in peritoneal washings both correlated with the histological
      grade, depth of tumour invasion, area of serosal invasion and peritoneal
      metastasis. The detection of free cancer cells in peritoneal washings by the
      telomeric repeat amplification protocol/enzyme-linked immunosorbent assay (TRAP
      ELISA) was significantly more sensitive than cytology or the CA125 immunoassay,
      suggesting that this could be used to diagnose early peritoneal dissemination.

PMID- 19761696
TI  - Haemorrhage detection in brain metastases of lung cancer patients using magnetic
      resonance imaging.
AB  - Magnetic resonance susceptibility-weighted imaging (SWI) is a new, highly
      sensitive technique used to detect haemorrhage. This study evaluated the ability
      of magnetic resonance imaging (MRI) to detect haemorrhage in 45 lung cancer
      patients with brain metastases and compared the results with T2*weighted imaging
      (T2*WI) and contrast-enhanced T1-weighted imaging (CE-T1WI). Eighty-nine
      haemorrhagic brain metastases were identified in 31 patients using SWI, 68 were
      identified in 23 patients using T2*WI and 46 were identified in 14 patients using
      CE-T1WI. Most micro-bleeds could only be identified by SWI. It was concluded that
      haemorrhage is a frequent occurrence in brain metastases originating from lung
      cancer and that haemorrhage can be detected using SWI in a majority of brain
      metastases patients.

PMID- 19761697
TI  - Up-regulation of CXC chemokine receptor 4 expression in chronic atrial
      fibrillation patients with mitral valve disease may be attenuated by renin
      angiotensin system blockers.
AB  - This study characterized CXC chemokine receptor 4 (CXCR4) expression in patients
      with mitral valve disease and chronic atrial fibrillation (AF). Forty-eight
      patients with chronic AF formed two groups based on whether they were treated
      with or without renin-angiotensin system (RAS) blockers (AF + RAS group; n = 25,
      or AF - RAS group; n = 23). The controls comprised 17 mitral valve disease
      patients with sinus rhythm (SR group). CXCR4 mRNA and protein levels in the left
      atria were significantly higher in the AF - RAS and AF + RAS groups than in the
      SR group. CXCR4 expression was significantly lower in the AF + RAS group than the
      AF - RAS group. More CD34(+) cells expressed CXCR4 in the AF - RAS and AF + RAS
      groups than in the SR group. Angiotensin II, collagen I and left atrial diameter
      significantly positively correlated with CXCR4 expression in the AF - RAS group.
      These results suggest that CXCR4 expression is up-regulated in chronic AF
      patients with mitral valve disease, is associated with atrial remodelling, and
      that these effects are attenuated by RAS blockers.

PMID- 19761698
TI  - Thyrotropin-releasing hormone can relieve cancer-related fatigue: hypothesis and
      preliminary observations.
AB  - Fatigue in cancer patients is highly prevalent, predominantly idiopathic,
      difficult to manage, and has a significant negative impact on quality of life.
      Thyrotropin-releasing hormone (TRH) exerts normotrophic, state-dependent
      therapeutic effects in a variety of experimental and clinical situations. To
      evaluate TRH as a treatment for cancer-related fatigue, an ongoing randomized,
      placebo-controlled, crossover pilot study of breast cancer patients has been
      initiated and this report presents preliminary observations conducted with three
      of these patients over 4 consecutive weeks, thereby involving a total of six TRH
      treatments and six saline controls. Global assessment using both subjective and
      objective parameters showed that TRH exerted clear anti-fatigue effects in four
      of the six TRH treatments. These responses were rapid in onset and persisted
      through the 24 h observation period. No anti-fatigue responses were seen in five
      of the six saline controls. No unexpected side-effects were seen with TRH
      administration. These initial findings support the proposal that TRH can
      ameliorate cancer-related fatigue.

PMID- 19761699
TI  - Intravenous fentanyl is exhaled and the concentration fluctuates with time.
AB  - Previous studies have reported that fentanyl is eliminated predominantly by
      hepatic biotransformation, and that some is eliminated unchanged in urine and
      stools. No reports have described the elimination of fentanyl via the lungs. In
      this study, exhaled gas samples from eight anaesthetized patients undergoing
      cardiac surgery were analysed using solid-phase microextraction (SPME) coupled
      with gas chromatography-mass spectrometry (GC-MS). Results confirmed that
      fentanyl was exhaled by patients after intravenous administration, that the
      concentration of exhaled fentanyl fluctuated with time and peak concentrations
      were reached approximately 15 - 20 min after intravenous fentanyl administration.
      Thus, in addition to hepatic biotrans formation and elimination via urine and
      faeces, fentanyl is also eliminated unchanged by the lungs. The potential risk to
      operating theatre personnel from long-term exposure to low levels of exhaled
      anaesthetic agents following intravenous administration to patients during
      surgery warrants further research.

PMID- 19761700
TI  - Treatment of chronic idiopathic urticaria with levamisole: a multicentre,
      randomized, double-blind, controlled trial.
AB  - The objective of this study was to evaluate the efficacy of treating chronic
      idiopathic urticaria (CIU) with levamisole in combination with levocetirizine.
      This was a multicentre, randomized, double-blind, controlled trial that included
      132 patients with active CIU who were treated for 6 weeks with either
      levocetirizine alone (control group; n = 65) or levamisole plus levocetirizine
      (treatment group; n = 67). Response to therapy was evaluated by measuring the
      efficacy rate. After 2 weeks of treatment, there was no significant difference in
      the efficacy rate between the treatment and control groups (54.84% and 42.37%,
      respectively). After 6 weeks of treatment, a statistically significant difference
      in the efficacy rate was observed between the groups (76.27% and 54.39% for the
      treatment and control groups, respectively). This study demonstrated that a
      combination of levamisole plus levocetirizine is more effective than
      levocetirizine alone and potentially provides a new, promising approach to the
      treatment of CIU.

PMID- 19761701
TI  - Accuracy of intra-operative frozen section analysis of ovarian tumours.
AB  - During operative treatment for ovarian tumours assistance is frequently required
      to make decisions regarding malignancy status and the extent of the ensuing
      procedure. Intra-operative frozen section analysis may be useful, provided there
      is adequate acquaintance with the correlation between using frozen sections and
      permanent histopathological sections for diagnosis at the institution where the
      operation is being undertaken. This retrospective study aimed to determine this
      correlation. Findings from 131 intra-operative frozen sections were compared with
      the subsequent diagnosis from permanent histopathological sections for women with
      benign, borderline and malignant ovarian tumours at the Maribor Teaching Hospital
      (now the University Clinical Centre Maribor) between 1 January 1993 and 31
      December 2001. Frozen-section findings corresponded to histopathological findings
      in 84.7% of cases, with 15.3% false-negative and no false-positive results. For
      benign, borderline and malignant ovarian tumours, sensitivity was 100.0%, 76.1%
      and 89.0%, respectively, and specificity was 90.6%, 90.6% and 100.0%,
      respectively. The majority of errors occurred in diagnosing mucinous borderline
      tumours. Precise pre-operative diagnosis is extremely important in the treatment
      of ovarian tumours.

PMID- 19761702
TI  - Association of programmed cell death factor 4 (PDCD4) with hepatocellular
      carcinoma and smoking in a Chinese male population.
AB  - Programmed cell death factor 4 (PDCD4) is one of the genes that has been found to
      be up-regulated during apoptosis and loss of PDCD4 expression has been found in
      many kinds of progressive carcinomas. The objective of this study was to
      investigate the interactions between PDCD4 and smoking status in hepatocellular
      carcinoma. This case-controlled study included 68 Chinese male patients with
      hepatocellular carcinoma who were classified as smokers or non-smokers according
      to their pack-years of smoking status. Samples were obtained from carcinoma and
      normal tissues and examined using Western blotting. The results indicated that
      levels of PDCD4 were significantly lower in hepatocellular carcinoma tissues
      compared with normal tissues and that, in normal tissue, PDCD4 levels in smokers
      were significantly lower than in non-smokers.

PMID- 19761703
TI  - Reliability and validity testing of the SF-36 questionnaire for the evaluation of
      the quality of life of Chinese urban construction workers.
AB  - The quality of life (QOL) of the Chinese 'floating' migrant population is of
      growing concern. Urban construction workers are the main migrant population in
      China, but there is little published research on their QOL. The reliability and
      validity of the 36-Item Short Form Health Survey (SF-36) questionnaire were
      assessed by conducting a population-based study of migrant construction workers
      in Shenyang, China. Two construction sites were randomly selected from each of
      the five districts of Shenyang City and 1200 copies of the questionnaire were
      distributed to rurally-registered, non-Shenyang workers aged > or = 16 years at
      these sites. A total of 1125 questionnaires were evaluated. The overall
      Cronbach's alpha coefficient of the SF-36 questionnaire was 0.821 while the
      respective Cronbach's alpha coefficient for each dimension was > 0.70. Results
      showed that the SF-36 questionnaire demonstrated good reliability and validity,
      and that it can be used to measure QOL among Chinese migrant urban construction
      workers.

PMID- 19761704
TI  - World Health Organization sub-types, initial treatment outcome and prognostic
      study of unselected adult patients with acute myeloid leukaemia in Shanghai: an
      analysis of 623 cases.
AB  - This study investigated the complete remission (CR) rate and survival of 623
      newly diagnosed patients with acute myeloid leukaemia (AML) in Shanghai, China,
      classified according to World Health Organization and French-American-British
      criteria, and compared the differences in treatment effect with those reported in
      developed countries and those reported in Shanghai from 1984 to 1994. Total CR
      rate was 66.5%, median survival was 18 months and estimated survival at 3 years
      was 30.8%. The 3-year relapse rate was 55.1%. These data showed that the CR rate
      was similar to that achieved in studies from developed countries, but long-term
      survival was worse. The CR rate and survival were increased markedly compared
      with data previously collected in Shanghai (1984 - 1994). Induction
      chemotherapeutic regimens based on idarubicin, daunorubicin or homoharringtonine
      all had similar CR rates and survivals. Karyotype was the most important
      prognostic factor. Multilineage dysplasia in de novo AML was not an independent
      prognostic factor. Improvement in the long-term treatment effect in China is an
      important challenge for the future.

PMID- 19761705
TI  - The relationship between Chinese construction workers' HIV/AIDS-related
      knowledge, attitudes and behaviour: a structural equation model.
AB  - This study explored the relationship between human immunodeficiency
      virus/acquired immune deficiency syndrome (HIV/AIDS)-related knowledge, attitudes
      and behaviour in migrant urban construction workers using structural equation
      modelling (SEM). A cross-sectional study was conducted among 428 male subjects on
      three building sites in Shenyang City. The SEM model of HIV/AIDS-related
      knowledge, attitudes and behaviour was built using LISREL version 8.5 and it
      fitted the data well, as shown by an adjusted goodness of fit index of 0.82 and a
      root mean square error of approximation of 0.094. Knowledge of HIV/AIDS was
      closely correlated with attitudes and behaviour. Age was an important factor
      affecting HIV/AIDS-related knowledge, attitudes and behaviour. These findings
      suggest that increasing HIV/AIDS-related knowledge could improve the attitude and
      behaviour of migrant urban construction workers, enabling them to avoid high-risk
      behaviour that increases the spread of HIV/AIDS. Any intervention used will need
      to take the important factor of age into consideration.

PMID- 19761706
TI  - Use of short echo time two-dimensional 1H-magnetic resonance spectroscopy in
      temporal lobe epilepsy with negative magnetic resonance imaging findings.
AB  - We evaluated short echo time two-dimensional 1H magnetic resonance spectroscopy
      (2D-1HMRS) with the point-resolved spatial selection (PRESS) protocol in temporal
      lobe epilepsy (TLE) patients with negative magnetic resonance imaging (MRI)
      findings and described the characteristics of 2D-(1)HMRS in the epileptic focus.
      Thirty-eight TLE patients with negative conventional MRI findings and 10 healthy
      controls were studied by 2D-1HMRS. A 128-channel prolonged video
      electroencephalographic (EEG) method was used as the standard for epileptogenic
      focus localization to evaluate N-acetyl aspartate/(choline + creatine +
      phosphocreatine) (NAA/[Cho + Cr-PCr]), glutamate + glutamine/creatine (Glx/Cr
      PCr) and myo-inositol/Cr-PCr ratios in patients with negative MRI findings. The
      2D-1HMRS showed that 32/38 patients and all healthy controls had stable baselines
      and good signal-to-noise ratios. Compared with the healthy controls, 32 patients
      showed abnormal NAA/(Cho + Cr-PCr) ratios in the hippocampus and, in 25 of these
      patients, focus lateralization agreed with the EEG. It is concluded that short
      echo time 2D-1HMRS with the PRESS protocol can help find abnormalities in
      lateralization of temporal epilepsy in patients with negative MRI findings.

PMID- 19761707
TI  - Recent trends in the distribution of common bile duct stones in urban South
      Koreans.
AB  - This retrospective, observational study was designed to analyse recent trends in
      the age distribution of westernized persons in South Korea with common bile duct
      stones (cholesterol, brown and black stones). Data on 253 patients who had
      received endoscopic surgery at a tertiary referral hospital in Daegu, the third
      largest South Korean city, were used to investigate the relationship between the
      numbers of patients with different types of common bile duct stones and age.
      There were strong correlations between age and the frequency of the three
      different types of common bile duct stones. The frequency of cholesterol stones
      decreased exponentially with increasing patient age, whereas the frequency of
      brown stones increased exponentially. Patients with black stones showed a
      Gaussian-like age distribution. Thus, the age-dependency of the frequency of
      these three common types of bile duct stones differed from one another within
      this patient population.

PMID- 19761708
TI  - Preferences of patients with post-menopausal osteoporosis treated with
      bisphosphonates--the VIVA II study.
AB  - The effectiveness of bisphosphonate treatment for post-menopausal osteoporosis
      depends on patients adhering to the therapeutic regimen. We previously showed
      that patients prefer a once-monthly regimen and the present follow-up study aimed
      to analyse patients' motivation for this preference. Women with post-menopausal
      osteoporosis (n = 2035) completed a questionnaire targeting their bisphosphonate
      treatment preferences. The majority had chosen the once-monthly regimen due to
      the comfort (69%) and simplicity (59%) of the treatment and the need to take
      fewer pills (55%). Friends, relatives and print media were highlighted as
      important sources of information and many patients indicated a need for more
      information about osteoporosis and its management. Gastrointestinal and muscular
      side-effects were reported by about one-third of the patients, but these were
      well tolerated. It is concluded that once-monthly bisphosphonate treatment was
      preferred due to improved quality of life and should be offered to all patients
      with post-menopausal osteoporosis.

PMID- 19761709
TI  - Distal trisomy of 10q with distal monosomy of 15q due to a paternal
      translocation.
AB  - Distal trisomy of 10q is a rare chromosomal abnormality. Distal deletions of the
      terminal long arm of chromosome 15 have rarely been described. We report on a
      male infant with low birth weight and microcephaly, a flat face with a spacious
      forehead, low-set ears, blepharophimosis, microphthalmia, a small nose, and a
      depressed nasal bridge. Microarray comparative genomic hybridization identified
      that he had the karyotype 46, XY, der (15) t (10;15) (q25.2;q26.2) pat, with
      chromosomal breakpoints at 10q25.2 and 15q26.2. This male neonatal case had an
      unbalanced translocation inherited from his father who was a balanced carrier
      with the karyotype 46, XY, t (10;15) (q25;q26). The neonate had a partial trisomy
      of the long arm of chromosome 10 with a partial monosomy of distal 15q. The
      clinical features were in agreement with previous descriptions and allowed us to
      propose a growth retardation phenotype for this neonate case.

PMID- 19761710
TI  - Adamantinoma of the tibia treated with a new intramedullary diaphyseal segmental
      defect implant.
AB  - In this case report, a 75-year old male presented with a mass on the anterior
      surface of the mid-shaft of the right tibia. Imaging studies showed a well
      circumscribed radiolucent lesion in the anterior tibial cortex, without soft
      tissue extension. Plain radiographs and computed tomography scan of the chest
      were negative. Histological diagnosis was consistent with adamantinoma, a rare
      primary bone tumour. Wide tumour resection of approximately 16 cm of the tibial
      diaphysis with a surrounding cuff of normal tissue was performed. The bone defect
      was reconstructed using an intramedullary diaphyseal segmental defect fixation
      system. At 26 months post-operatively the patient is alive with no evidence of
      local recurrence, distant metastases or implant failure. The intramedullary
      diaphyseal segmental defect fixation system is associated with excellent
      oncological and functional outcomes. Intra-operative modularity, ease of
      application, immediate post-operative stability and rapid rehabilitation are the
      major advantages of this diaphyseal prosthesis.

PMID- 19761711
TI  - Transient cortical blindness after coronary angiography.
AB  - Transient cortical blindness is rarely encountered after angiography of native
      coronary arteries or bypass grafts. This paper reports a case of transient
      cortical blindness that occurred 72 h after coronary angiography in a 56-year old
      patient. This was the patient's fourth exposure to contrast medium. Neurological
      examination demonstrated cortical blindness and the absence of any focal
      neurological deficit. A non-contrast-enhanced computed tomographic scan of the
      brain revealed bilateral contrast enhancement in the occipital lobes and no
      evidence of cerebral haemorrhage, and magnetic resonance imaging of the brain
      showed no pathology. Sight returned spontaneously within 4 days and his vision
      gradually improved. A search of the current literature for reported cases of
      transient cortical blindness suggested that this is a rarely encountered
      complication of coronary angiography.

PMID- 19761712
TI  - Primary intrapulmonary thymomas: case report and review of the literature.
AB  - Primary intrapulmonary thymomas (PIT), which are intrapulmonary tumours without
      an associated mediastinal component, are very rare; only 29 cases of PIT have
      been described in the literature since 1951. This report presents a case of PIT
      in a 59-year old Chinese woman with a type A thymoma (including its pathogenesis,
      clinical pathological characteristics, immunological phenotype, treatment and
      prognosis), in the context of a review of the current literature. The origin of
      thymomas in this unusual location remains unknown. In this case,
      immunohistochemical analysis demonstrated that the epithelial component was
      strongly positive for cytokeratin and focally reactive for epithelial membrane
      antigen. It is concluded that PIT should be considered when the histopathological
      appearance of a lung tumour is not typical of other pulmonary neoplasms. Complete
      resection appears sufficient in non-malignant tumours, while in cases of partial
      resection or malignancy, adjuvant radiotherapy should be considered. Long-term
      regular clinical follow-up is also warranted, due to the risk of late local
      recurrence.

PMID- 19761713
TI  - Meta-analysis of recent studies on patients admitted to hospital due to adverse
      drug effects.
AB  - The use of drugs has expanded during the previous decade. However, earlier
      studies on patients admitted for adverse drugs effects (ADEs) have been
      heterogeneous. The objectives of this study were to assess the number of recent
      admissions to hospital due to ADEs and to assess the degree of heterogeneity in
      recent studies. Prospective studies published in the past decade were therefore
      pooled and compared with the pooled results from earlier studies. The pooled
      overall percentage in recent studies (n = 20) was 5.4% (5.0 - 5.8) and this did
      not significantly differ from that in the earlier studies (n = 21, pooled
      percentage 4.7%, 3.1 - 6.2). The studies were clinically very heterogeneous with
      percentages of ADEs between 3.4 and 33.2%. The nature of the patient group could
      be held largely responsible for the clinical heterogeneity observed.

PMID- 19761714
TI  - Characterization of the behavior of alginate-based microcapsules in vitro and in
      vivo.
AB  - OBJECTIVES: Functional formulations providing protection of nutritional products
      against gastric juice or a capable of delivering them to distinct areas of the
      gastrointestinal tract are increasingly utilized by the food industry. However,
      the application of functional excipients that are established in pharmaceutical
      applications is limited in case of food products, as they are typically not
      classified as Generally Recognized As Safe (GRAS). MATERIALS: Accordingly, we
      investigated whether two alginate-based microcapsule preparations (capsule
      diameter 1 - 2 mm) either based on alginate and maize starch (MS-type) or
      alginate and casein (OCF27-type) and both created from ingredients classified as
      food supplements provide functional properties with respect to regional
      gastrointestinal targeting. METHODS: For this purpose the in vitro disintegration
      and swelling of the microcapsules was tested in various media. Furthermore,
      individual microcapsules, magnetically labelled with 100 - 200 microg black iron
      oxide, were ingested by healthy volunteers under fasting and fed conditions.
      Gastrointestinal transit as well as the gastrointestinal disintegration behavior
      were determined by using Magnetic Marker Monitoring. RESULTS: The results of in
      vitro and in vivo investigations show that both types of microcapsules are
      resistant to gastric juice for approximately 10 hrs under fasting and fed
      conditions. However, the disintegration characteristics of the two types of
      microcapsules within the intestines are different. CONCLUSION: Whilst the MS-type
      of capsules disintegrated predominantly within the small intestine shortly after
      gastric emptying, the OCF27-type of capsules underwent a rather slow
      disintegration predominantly in the colon.

PMID- 19761715
TI  - Evaluation of the pharmacokinetic interaction between esomeprazole (40 mg) and
      acetylsalicylic acid (325 mg) in healthy volunteers.
AB  - OBJECTIVE: To evaluate the effect of esomeprazole on the pharmacokinetics of low
      dose acetylsalicylic acid (ASA) during repeated co-administration. METHODS: This
      was an open, randomized, 3-way crossover study in 55 healthy volunteers.
      Treatment periods comprised 5 days' oral esomeprazole (40 mg) or ASA (325 mg)
      alone, or in combination, separated by washout of >or= 13 days. The primary
      pharmacokinetic end points were steady-state area under the concentration-time
      curve (AUCtau) and observed maximum plasma concentration (Cmax) of ASA +/-
      esomeprazole. RESULTS: The estimates (90% confidence interval) of the geometric
      mean ratios for AUCtau and Cmax of ASA +/- esomeprazole were 1.04 (1.00 - 1.09)
      and 1.12 (1.03 - 1.22), respectively. Corresponding results for esomeprazole +/-
      ASA were 0.93 (0.89 - 0.98) and 0.96 (0.91 - 1.01), respectively. Administration
      of esomeprazole and ASA in combination was well tolerated. CONCLUSIONS: There was
      no pharmacokinetic interaction between esomeprazole (40 mg) and ASA (325 mg)
      during repeated co-administration in healthy volunteers.

PMID- 19761716
TI  - Influence of age, gender, and race on pharmacokinetics, pharmacodynamics, and
      safety of fesoterodine.
AB  - OBJECTIVE: Fesoterodine, a new antimuscarinic agent for overactive bladder,
      undergoes immediate and extensive hydrolysis by nonspecific esterases to 5
      hydroxymethyl tolterodine (5-HMT), the metabolite principally responsible for its
      antimuscarinic activity. Formation of 5-HMT does not require cytochrome P450
      (CYP)-mediated metabolism, but its further metabolism and inactivation involves
      CYP3A4 and CYP2D6 isoenzymes. Subject age, gender, and race can play a key role
      in inter-subject variability in pharmacokinetics and thus efficacy and safety of
      drugs. This article examines the effects of age, gender, and race on the
      pharmacokinetics and pharmacodynamics of fesoterodine. METHODS: Data from two
      randomized, double-blind, placebo-controlled, parallel-group trials in healthy
      subjects are presented: Study 1 investigated the effects of race (white vs. black
      men) and Study 2 investigated the effects of age (young vs. old men) and gender
      (elderly men vs. elderly women) on the pharmacokinetics and pharmacodynamics of
      single doses of fesoterodine 8 mg. In both studies, the primary endpoints were
      area under the concentration-time curve up to the last sample (AUC0-tz) and
      maximum concentration (Cmax) of 5-HMT in plasma. Pharmacodynamic variables
      included spontaneous salivary secretion (Studies 1 and 2) and residual urine
      volume (Study 2 only). The two studies included 5 groups of 16 subjects each
      (randomized 3 : 1 to fesoterodine or placebo): white men aged 18 - 45 years,
      black men aged 18 - 45 years (Study 1); young white men aged 18 - 40 years,
      elderly white men aged > 65 years, and elderly white women aged > 65 years (Study
      2). RESULTS: There were no clinically meaningful differences in the primary
      endpoints between white and black subjects or between young white men, elderly
      white men, and elderly white women. Mean AUC0-tz was 70.7 ng/ml x h in whites and
      64.1 ng/ml x h in blacks; mean Cmax was 6.1 and 5.5 ng/ml in whites and blacks,
      respectively. Mean AUC0-tz in young white men, elderly white men, and elderly
      white women was 49, 48, and 54 ng/ml x h, respectively; mean Cmax in young white
      men, elderly white men, and elderly white women was 4.1, 3.8, and 4.6 ng/ml,
      respectively. Consistent with the anticholinergic pharmacology of fesoterodine,
      declines in salivary volume were observed in both studies, and elevations in
      residual urinary volume were observed, especially in elderly subjects, in Study
      2. Fesoterodine was well tolerated, with common adverse events such as headache
      and dry mouth recognized as antimuscarinic class effects. CONCLUSIONS: Subject
      demographics, such as age, gender, and race, do not have a clinically meaningful
      effect on 5-HMT pharmacokinetics or pharmacodynamics after single-dose
      administration of fesoterodine 8 mg; thus, no dosage adjustment is required for
      fesoterodine based on age, gender, or race.

PMID- 19761717
TI  - Comparative study of dihydroartemisinin and artesunate safety in healthy Thai
      volunteers.
AB  - OBJECTIVE: As part of new drug development initiatives in Thailand, a new tablet
      formulation of dihydroartemisinin (DHA, an antimalarial drug) has been developed.
      Our previous bioequivalence study indicated that the new and reference DHA
      formulations were well tolerated; however, a significant decrease in hemoglobin
      was detected after a single 200-mg oral dose. To explore further, a clinical
      study with an emphasis on hematological parameters was conducted. METHODS: A
      single-center, randomized, single-blind, cross-over clinical study was conducted
      in 18 healthy volunteers with a dosage of 300 mg daily for 2 days. Artesunate was
      used as a comparator. Adverse events were monitored and laboratory parameters on
      study Days 0, 2, 5, and 7 post drug administrations were analyzed. RESULTS:
      Eighteen volunteers completed both rounds of the study. Both drugs were well
      tolerated. All adverse events were mild. Significant decrease in hemoglobin
      compared to baseline was detected for both drugs 7 days after administration
      (DHA: 0.48 g/dl, p = 0.007; artesunate 0.38 g/dl, p = 0.001). Transient bone
      marrow suppression was evidenced by reduction of reticulocytes with a lowest
      number on study Day 5 (artesunate 75% reduction in reticulocyte count; DHA 47%, p
      < 0.001 for both drugs compared to baseline). CONCLUSION: The present study
      confirmed our previous finding on significant decrease in hemoglobin. Artesunate
      appeared to have more negative effects on the numbers of reticulocytes and white
      blood cells than DHA. Systemic laboratory and toxicity profiles presented in this
      study may be used as a framework for future clinical studies of artemisinin and
      its derivatives.

PMID- 19761718
TI  - Absolute bioavailability and pharmacokinetics of avosentan in man.
AB  - OBJECTIVE: Avosentan is a potent, selective endothelin A receptor blocker. The
      pharmacokinetics of avosentan were investigated in healthy male and female
      volunteers, following oral and i.v. administration of single doses of avosentan
      and its absolute bioavailability was determined. METHODS: In a randomized,
      balanced open-label, three-period oral crossover study, 26 healthy subjects (19
      males and 7 females) received Treatments A, B and C. Treatment A consisted of a
      single dose of a 25 mg film-coated tablet of avosentan, Treatment B of a single
      dose of a 50 mg film-coated tablet of avosentan and Treatment C of 10 mg
      avosentan in 20 ml solution for infusion for 20 minutes (10 mg avosentan in 20 ml
      phosphate buffer pH 9.0 containing 1% polysorbate 20). Plasma concentrations of
      avosentan and its hydroxymethyl metabolite Ro 68-5925 were measured by liquid
      chromatography-tandem mass spectrometry. RESULTS: The absolute bioavailability
      values (compared with i.v. infusion) for the 25 and 50 mg film-coated tablets
      were 81% and 72%, respectively. The extent of absorption, as measured by partial
      and total AUC, increased almost proportionally with the dose. The estimated
      proportionality coefficient for AUC0- yen was 1.12 (90% CI 1.06, 1.18). For the
      rate of absorption (Cmax) strict dose-proportionality was not demonstrated
      (proportionality coefficient 1.13 (90% CI 1.0, 1.28)). No relevant gender
      differences in the pharmacokinetic characteristics were evident after a single
      i.v. dose and at an oral dose of 25 mg, whereas after oral administration of 50
      mg of avosentan differences were seen in Cmax and t1/2. CONCLUSION: The absolute
      bioavailability of avosentan film-coated tablets is high, i.e. 70 - 80%.

PMID- 19761719
TI  - IgA nephropathy in the triethnic population of New Mexico.
AB  - AIMS: IgA nephropathy (IgAN) is the most frequent glomerulonephritis around the
      globe, but its incidence in the United States is unknown. The disease has a
      preponderance for certain racial/ethnic groups. Our goals were to retrospectively
      analyze a series of IgAN biopsies from the state of New Mexico and to calculate
      an estimated incidence. Then we compared the racial/ethnic composition of our
      patient cohort to the composition of the New Mexico population and examined the
      three main racial/ethnic groups for differences in clinical and pathologic
      parameters. MATERIALS AND METHODS: Renal biopsies and clinical data from IgAN
      cases newly diagnosed in New Mexico between 2000 and 2005 were reviewed. We
      compared the racial/ethnic composition of our patient cohort to the demographic
      composition of the New Mexico population. Demographic, clinical, and
      histopathologic variables were analyzed with respect to the patients'
      race/ethnicity. RESULTS: The incidence of IgAN in New Mexico was 10.2 cases per
      million persons per year (9.3 when Henoch-Schonlein purpura cases were excluded).
      American Indians were twice as frequent in our patient cohort when compared to
      their demographic representation, with the reverse finding for Non-Hispanic
      Whites. Hispanics more frequently had nephrotic range proteinuria than Non
      Hispanic Whites and American Indians. On renal biopsy, endocapillary
      proliferative glomerulonephritis was the most common glomerular abnormality,
      followed by the focal segmental glomerulosclerosis (FSGS)-like pattern. The FSGS
      like pattern was more frequent in American Indians and Hispanics than in Non
      Hispanic Whites. CONCLUSIONS: This is the first report of an incidence figure of
      IgAN for an entire state in the US. American Indian and Hispanic patients had a
      stronger representation in our cohort than Non-Hispanic Whites, when compared to
      the general New Mexico population.

PMID- 19761720
TI  - Low-flux hemodialysis suppresses interferon-gamma production: the possible role
      of beta2-microglobulin.
AB  - Interferon-gamma (IFN-gamma) is required for the acquired immune response
      involving maturation and activation of antigen-presenting cells (APC); both IFN
      gamma production and activation of APC are impaired in ESRD patients on low-flux
      hemodialysis (HD). High levels of uremic toxins including beta2-microglobulin
      (beta2M) are thought to play a role in immunosuppression. PATIENTS AND METHODS:
      To test this hypothesis, we conducted an A-B-A crossover study to examine the
      influence of high-flux HD (A) versus low-flux HD (B) in ESRD patients (n = 14)
      using biocompatible synthetic dialyzer membranes (Polyamix(R), Gambro, Hechingen,
      Germany) and ultrafiltered bicarbonate-buffered dialysis fluid. Each study period
      lasted 6 months and at the end of each period, Kt/V urea, plasma levels of
      albumin, C-reactive protein (CRP) and beta2M were determined. In addition,
      production of IFN-gamma induced by heat-killed Staphylococcus epidermidis (Staph
      epi) was performed in whole blood cultures. RESULTS: Kt/V urea (mean +/- SEM) was
      1.45 +/- 0.06 in Period A, 1.36 +/- 0.07* in Period B, and 1.51 +/- 0.07 in
      Period A' (*p < 0.01). beta2M resting levels increased from 26.6 +/- 1.42 mg/l in
      Period A to 34.7 +/- 2.30* mg/l in Period B, and decreased to 21.6 +/- 1.07 mg/l
      at the end of Period A' (*p < 0.0001). Albumin and CRP levels did not differ
      significantly. Staph epi-induced IFN-gamma production was 1.2 +/- 0.39 ng/1,000
      PBMC at the end of Period A, 0.34 +/- 0.10 ng/1,000 PBMC* in Period B, and 2.71
      +/- 0.67 ng/1,000 PBMC at the end of Period A' (*p < 0.05). There was an inverse
      correlation between b2M levels and whole blood IFN-gamma production (R2 = 0.26).
      CONCLUSION: High levels of uremic toxins such as beta2M suppress IFN-gamma
      production in ESRD patients under low-flux HD. High-flux HD reduces beta2M levels
      by 30% and improves IFN-gamma production suggesting an improved cellular immune
      response in ESRD patients.

PMID- 19761721
TI  - Immediate pain sensation is less with subcutaneous epoietin-beta compared to
      subcutaneous darbepoietin-alpha.
AB  - Although immediate pain sensation at the injection site is reported by patients,
      only limited data on comparison of pain at the injection site between
      erythropoiesis stimulating agents are available. Therefore, we compared the
      effect of subcutaneous epoietin-beta on immediate pain sensation to that of
      subcutaneous darbepoietin-alpha in a double blind, randomized controlled study.
      Adult patients, aged 18 - 75 years, treated with peritoneal dialysis or with
      stage 4 chronic kidney disease who in our unit are treated with subcutaneous
      darbepoietin-alpha for renal anemia for at least 3 months, were eligible for the
      study. After informed consent, patients received on one day four subcutaneous
      injections, two in each upper leg, in a fixed sequence, blinded to the patient
      and blinded to the investigator. Injections contained in a random order single
      dose epoietin-beta (0,3 ml = 4000 IU), darbepoietin-alpha (0,5 ml = 20 microg)
      and volume matched saline 0.9% placebo injections. Immediately after the four
      injections, whilst remaining sitting, the subject was requested to fill out one
      pain scale (Visual Analogue Scale (VAS)) and to verbally evaluate the pain
      experience (Verbal Pain Score (VPS)). Finally, the subject was requested to rank
      the four injections from least to most painful (Treatment Ranking). A total of 42
      patients (22 male) participated in the study with a mean age of 56.8 +/- 1.9
      years. The average VAS was lower for epoietin-beta (26.8 +/- 4.5 mm) compared to
      darbepoietin-alpha (58.1 +/- 4.6 mm; p < 0.01). Mean VAS for epoietin-beta did
      not differ from that of the two placebo saline solutions (0,3 ml 26.3 +/- 4.4 mm;
      0,5 ml 18.4 +/- 3.2 mm). Mean VAS for darbepoietin-alpha was significantly higher
      than placebo (both p < 0.01). Similar observations were obtained for VPS (mean
      for epoietin-beta 1,3 +/- 0.2 and for darbepoietin-alpha 2.9 +/- 0.2; p < 0.01)
      and Treatment Ranking (mean for epoietin-beta 2.0 +/- 0.2 and for darbepoietin
      alpha 3.2 +/- 0.2; p < 0.01). From the results it can be concluded that
      subcutaneous epoietin-beta caused statistically significant less pain sensation
      immediately after injection compared to subcutaneous darbepoietin-alpha . The
      pain caused by subcutaneous epoietin-beta injection was similar to that caused by
      placebo control injections whereas subcutaneous darbepoietin-alpha injection was
      significantly more painful than subcutaneous placebo injections.

PMID- 19761722
TI  - Slower decline of renal function after initiation of rosiglitazone in diabetics -
      a pilot study.
AB  - BACKGROUND: To translate laboratory data to the bedside, we hypothesized that
      initiation of a thiazolidinedione would reduce the rate of progression of renal
      insufficiency in diabetic subjects. METHODS: We included subjects initiated on
      rosiglitazone for control of diabetes who had at least two consecutive serum
      creatinine values >= 1.5 mg/dl that were at least 4 weeks apart. We used slope
      estimates of reciprocal of creatinine vs. time (days) from linear models to
      derive the rate of decline of renal function before (Phase 1) and after (Phase 2)
      rosiglitazone initiation. The adjusted rate of decline of renal function was
      derived using repeated measure models weighted by inverse variances adjusting for
      hemoglobin A1C and mean blood pressure. RESULTS: There were 114 subjects (113
      men, 1 woman; mean age 66.8 +/- 9.4 years). The mean duration of Phase 1 was
      586.2 +/- 275.6 days and Phase 2 was 613.2 +/- 281.7 days (p = 0.47). The mean
      unadjusted Phase 1 slope of reciprocal creatinine vs. time was -0.00015 +/-
      0.00021 and the Phase 2 slope was -0.00009 +/- 0.00021. The mean slope difference
      (Phase 2 - Phase 1) was 0.00005 +/- 0.00031 (p < 0.0001 for Wilcoxon signed rank
      test and p = 0.0023 for t-test). The adjusted difference in the mean slope was
      0.00007 +/- 0.00042 (p = 0.0135). CONCLUSION: There was a slower rate of decline
      of renal function after initiation of rosiglitazone in diabetic subjects with
      renal insufficiency. These findings warrant confirmation by a prospective
      randomized trial.

PMID- 19761723
TI  - Acute kidney injury requiring hemodialysis in patients with anicteric
      leptospirosis.
AB  - BACKGROUND: Leptospirosis is an infrequent disease in the US, with most cases
      reported in the state of Hawaii. Renal involvement is common (44 - 67%), ranging
      from a mild prerenal azotemia in anicteric disease to renal failure requiring
      dialysis in Weil's syndrome (severe leptospirosis with jaundice, renal failure,
      and hemorrhage). METHODS: To describe the pattern of leptospiral renal disease at
      our institution, we performed a retrospective analysis (1992 - 2004) of all
      hospitalized cases of laboratory confirmed leptospirosis presenting with acute
      kidney injury (AKI), defined as a presenting serum creatinine > 1.5 mg/dl.
      RESULTS: During this time period, 18 patients were hospitalized with laboratory
      confirmed leptospirosis. Among these patients, 12 had AKI on presentation, and
      hemodialysis was required in 3 patients. Renal biopsies were performed in 2 of
      these patients, revealing acute tubulointerstitial nephritis. Interestingly, the
      patients who required dialysis did not have Weil's syndrome. They did not exhibit
      jaundice or hemorrhage, and serum AST (mean 51.7 U/l (range 36 - 60)), ALT (mean
      51.0 U/l (range 38 - 64)), and total bilirubin (mean 1.2 mg/dl (range 0.8 - 1.8))
      were either within normal limits or only slightly elevated, despite having the
      worst renal disease. CONCLUSIONS: This series adds to other evidence that severe
      AKI (requiring dialysis) can complicate anicteric leptospirosis in contrast to
      the notion that the AKI in anicteric disease is typically mild and prerenal.
      Leptospirosis should be considered in all patients who present with fever and
      AKI, especially if associated with thrombocytopenia or travel to an endemic area.

PMID- 19761724
TI  - Anticardiolipin antibodies in hemodialysis patients with hepatitis C and their
      role in fistula failure.
AB  - BACKGROUND/AIMS: Several conflicting results are presently reported regarding
      raised IgG and IgM-anticardiolipin antibodies (ACA) titers in hemodialysis (HD)
      patients and their role in vascular access dysfunction. We aimed to determine the
      prevalence of both IgM and IgG-ACA titers and to analyze retrospectively their
      role in primary and secondary arteriovenous fistula (AVF) failure in a
      homogeneous group of HD patients with chronic hepatitis C. METHODS: This study
      included 103 adults on maintenance hemodialysis with chronic hepatitis C
      infection. All participants had blood samples drawn predialysis and after an
      overnight fast. Analysis included biochemistry, IgG and IgM ACA, Anti-HCV, HBsAg,
      serum HCV RNA and HCV genotyping. RESULTS: The prevalence of IgG-ACA was 14.6%
      (15/103). No patient had a positive value of the IgM-ACA test. HCV replication
      was detected in 52 of 76 patients. The most common HCV genotype was genotype 1
      (90%). The percentage of females was higher in ACA(+) group (p = 0.038). There
      were no significant differences between subjects with and without ACA-IgG
      regarding other parameters studied. No difference in regard to AVF survival was
      detected between ACA(+) and ACA(-) groups (p > 0.05). CONCLUSION: We found no
      significant differences in primary or secondary AVF failure between patients with
      elevated and normal ACA. Therefore, we conclude that AVFF may be caused by
      factors other than ACA in these patients. More prospective studies are needed to
      confirm this observation.

PMID- 19761725
TI  - Improvement in secondary hyperparathyroidism due to drug adherence monitoring in
      dialysis patients.
AB  - BACKGROUND: Poor medication adherence is a frequent cause of treatment failure
      but is difficult to diagnose. In this study we have evaluated the impact of
      measuring adherence to cinacalcet-HCl and phosphate binders in dialysis patients
      with uncontrolled secondary hyperparathyroidism. METHODS: 7 chronic dialysis
      patients with iPTH-levels >= 300 pg/ml despite treatment with >= 60 mg cinacalcet
      HCl were included. Medication adherence was measured using the "Medication Events
      Monitoring System" during 3 months, followed by another 3-month period without
      monitoring. The adherence results were monthly discussed with the patients, as
      well as strategies to improve them. RESULTS: During monitoring, the percentage of
      prescribed doses taken was higher for cinacalcet-HCl (87.4%) and sevelamer
      (86.3%) than for calcium acetate (76.1%), as was the taking adherence (81.9% vs.
      57.3% vs. 49.1%) but not the percentage of drug holidays (12.3% vs. 4.5% vs.
      3.6%). Mean PO4 levels (from 2.24 +/- 0.6 mmol/l to 1.73 +/- 0.41 mmol/l; p =
      0.14) and Ca++ x PO4 product (4.73 +/- 1.43 to 3.41 +/- 1.04 mmol2/l2; p = 0.12)
      improved and iPTH-level improved significantly from 916 +/- 618 pg/ml to 442 +/-
      326 pg/ml (p = 0.04), without any change in medication. However, as drug
      monitoring was interrupted, all laboratory parameters worsened again.
      CONCLUSIONS: Assessment of drug adherence helped to document episodes of non
      compliance and helped to avoid seemingly necessary dose increases.

PMID- 19761726
TI  - Nephrotic syndrome as paraneoplastic manifestation of a primary pulmonary
      lymphoepithelioma-like carcinoma.
AB  - We present a case of nephrotic syndrome secondary to a membranous
      glomerulonephritis (MG), in a nonsmoking female with a solitary pulmonary nodule,
      which did not show growth during 2 years of followup. A biopsy by
      videothoracoscopy showed a granulomatous non-neoplastic process with giant
      multinucleated cells. The appearance of a nephrotic syndrome and its
      interpretation as paraneoplastic revealed the existence of a primary pulmonary
      lymphoepithelioma-like carcinoma (LELC), a very rare pulmonary tumor. After
      resection of tumor there was a complete recovery from the nephrotic syndrome.
      This case highlights how the investigation of paraneoplastic syndromes can help
      in the early diagnosis of some malignancies.

PMID- 19761727
TI  - Acute on chronic subdural hematoma as a rare complication in a microscopic
      polyangiitis patient receiving antithrombotic treatment.
AB  - We report a 56-year-old man with microscopic polyangiitis (MPA) who developed
      acute exacerbation of a chronic subdural hematoma (SDH). Laboratory data
      demonstrated elevation of myeloperoxidase antineutrophil cytoplasmic antibody
      (MPOANCA) and rapidly progressing renal dysfunction. Renal biopsy showed
      crescentic glomerulonephritis (GN) with membranous nephropathy (MN). He was
      treated with corticosteroids, antithrombotic agents, and an immunosuppressant.
      One month after initiation of treatment, he had a mild headache. One month later,
      he developed acute SDH. Although he recovered completely after the operation, he
      finally died of bacterial infection. On autopsy, a scar of vasculitis was
      confirmed in the leptomeninges as well as in the kidney and lung. Although SDH is
      a rare complication in MPA, nephrologists must pay more attention to the initial
      symptoms before a hematoma attack such as headache, especially in patients using
      antithrombotic agents.

PMID- 19761728
TI  - Minimal-change nephrotic syndrome due to occupational mercury vapor inhalation.
AB  - A 25-year-old man developed nephrotic syndrome and severe hypertension following
      occupational exposure to mercury vapor whilst working at a fluorescent light
      factory. A renal biopsy confirmed minimal-change disease on light microscopy,
      immunofluorescence and electron microscopy. He was also noted to be polycythemic
      which was initially treated with venesection. His blood and urinary mercury
      levels were elevated and so he was given chelation therapy with 2,3
      dimercaptopropane-1-sulfonate (DMPS), along with steroids for his minimal-change
      disease, resulting in full resolution of his nephrotic syndrome within 6 weeks.
      He remains well with normal renal function, blood pressure and normal blood and
      urine mercury concentrations.

PMID- 19761729
TI  - Cardiac tamponade following insertion of an internal jugular vein catheter for
      hemodialysis.
AB  - Central venous cannulation is widely used in patients with end-stage renal
      disease when venous access was not adequately created in advance to be
      functioning when replacement therapy is required. As with all invasive
      procedures, central venous cannulation is associated with a number of
      complications. Cardiac tamponade is a well-recognized complication of this
      procedure and its mortality is high. It is thought to arise from the guide-wire,
      dilator and venous cannulation perforating the right atrium, right ventricle and,
      on rare occasions, the superior vena cava. In this study we describe a case of
      cardiac tamponade that was caused by perforating the inferior vena cava (IVC) via
      the guide-wire while attempting internal jugular vein (IJV) catheterization under
      echographic guidance.

PMID- 19761730
TI  - Renal amyloidosis in intravenous heroin addicts with nephrotic syndrome and renal
      failure.
AB  - BACKGROUND: Renal amyloidosis has emerged as an important differential diagnosis
      when heroin addicts are admitted to renal clinics with proteinuria and nephrotic
      syndrome. MATERIAL: We present nine heroin addicts with renal AA amyloidosis, a
      condition previously not encountered in Norway, who were admitted to our renal
      clinic during the last 3.5 years. In the same time period a total of 209 patients
      were biopsied from native kidneys. RESULTS: Heroin abuse was associated with 70%
      of all biopsy-verified renal AA amyloidosis during this time period. Renal
      amyloidosis was found in 9 of the 12 heroin addicts that were biopsied. 6 of the
      9 heroin addicts with amyloidosis required dialysis within 13 months after
      admission. CONCLUSION: Renal AA amyloidosis among heroin addicts seems to be
      associated with chronic suppurative skin infections. AA amyloidosis should always
      be considered in chronic heroin addicts presenting with proteinuria and renal
      impairment.

PMID- 19761731
TI  - Cryptococcal pleuritis developing in a patient on regular hemodialysis.
AB  - A 64-year-old male on regular hemodialysis who was a human T lymphotrophic virus
      Type I (HTLV-I) carrier developed cryptococcal pleuritis. The initial
      manifestations of the present case were a persistent cough and the accumulation
      of unilateral pleural effusion. A culture of the pleural fluid of the patient
      grew cryptococcus neoformans and a test for antigens against cryptococcus
      neoformans in the pleural fluid was also positive, therefore, cryptococcal
      pleuritis was diagnosed. Pleural cryptococcosis per se is rare and it is
      extremely rare for a dialysis patient to develop pleural cryptococcosis. To our
      knowledge, only a few cases of cryptococcal pleuritis have so far been reported
      in patients on dialysis. Furthermore, an isolated occurrence of cryptococcal
      pleuritis with no cryptococcal pulmonary parenchymal lesions, as was seen in the
      present case, is rare because cryptococcal pleuritis is usually associated with
      underlying cryptococcal pulmonary parenchymal lesions. Patients on chronic
      dialysis are susceptible to developing pleural effusion from many etiologies such
      as congestive heart failure, infection (tuberculosis, bacterial, viral,
      parasitic, fungal), collagen vascular disease, drug reaction, metastasis, or
      uremia itself. Cryptococcal pleuritis developing in a dialysis patient is
      extremely rare, but physicians should consider cryptococcal infection as a
      possible cause when pleural effusion develops in a dialysis patient and no other
      cause is identified, as occurred in the present case.

PMID- 19761732
TI  - Renal infarction after cocaine abuse: a case report and review.
AB  - A 36-year-old male presented with sudden pain in the left lower abdomen caused by
      a left renal infarction. Cocaine metabolites were found in the urine and a
      cocaine-induced renal infarction was diagnosed. Cocaine-induced renal infarction
      is not frequently reported in the literature. Pathophysiologic mechanisms include
      direct cocaine-induced platelet activation in combination with vasoconstriction
      and endothelial damage. There is no proven therapy for this complication.

PMID- 19761733
TI  - Aliskiren corrects recurrent hyperreninemia and hyperaldosteronism in autosomal
      dominant polycystic kidney disease.
AB  - A 47-year-old woman with family history of autosomal-dominant polycystic kidney
      disease (ADPKD), who underwent living-donor kidney transplantation in 2000,
      presented with recurrent edema, hyperreninemia, and hyperaldosteronism. Since
      2002, her antihypertensive therapy comprised ramipril and spironolactone. The
      post-transplantation kidney function was stable. Based on the clinical picture
      and reports of renin secretion by renal cysts in ADPKD, we performed a trial of
      aliskiren therapy (300 mg/day). The patient showed excellent blood pressure
      control and reduction of edema, with aldosterone levels normalizing within 2
      months. This is a novel report of aliskiren therapy for treatment of edema,
      hyperreninemia, and hyperaldosteronism in ADPKD.

PMID- 19761734
TI  - Profound thrombocytopenia associated with piperacillin in a hemodialysis patient.
AB  - Piperacillin-induced thrombocytopenia, albeit reversible, is a life-threatening
      hematological emergency but easily overlooked. We describe a 78-year-old uremic
      man on regular hemodialysis who received intravenous administration of
      piperacillin (2 g) 3 times a day to treat nosocomial pneumonia. On the eighth day
      of therapy, isolated profound thrombocytopenia with a nadir value of 3 x 103/mm3
      was noticed. Physical examination revealed multiple bruises over puncture sites
      and petechiae over bilateral lower extremities. An exhaustive search for
      potential causes of thrombocytopenia was unrevealing. Upon withdrawal of
      piperacillin and immediate high-flux hemodialysis, platelet count rapidly
      normalized up to 215 x 103/ mm3 in 3 days. With the widespread use of
      piperacillin, early recognition of piperacillin-induced immune thrombocytopenia
      and prompt withdrawal of the causative antibiotic may achieve less morbidity.

PMID- 19761735
TI  - Influence of darbepoetin-alpha therapy on HbA(1c) values in hemodialysis
      patients.

PMID- 19761736
TI  - Biogeographical origin and varicella risk in the adult immigration population in
      Catalonia, Spain (2004-2006).
AB  - Immigrants to the European Union may have a higher susceptibility to varicella
      zoster virus primo-infection than the indigenous population. There is no evidence
      as yet that this is caused by genetic or social factors. Therefore,
      susceptibility could be due to a lesser transmission of the virus in their
      ecosystems of origin. A multicentre observational study was performed from July
      2004 to June 2006 in four primary healthcare centres in Catalonia, Spain,
      monitoring varicella incidences and comparing standardised incidence rates and
      standardised rate ratios among different populations classified according to
      their biogeographical origin (holarctic, Asian paleotropical, African
      paleotropical or neotropical). Overall, 516 varicella cases were recorded. The
      standardised incidence rates per 1,000 inhabitants per year were: holarctic: 2.17
      (95% confidence interval (CI): 1.95-2.39); autochthonous 2.26 (95% CI: 2.03
      2.49); immigrants 3.59 (95% CI: 2.92-4.26); neotropical 4.50 (95% CI: 3.28-5.71);
      non-holarctic 5.38 (95% CI: 4.27-6.14); Asian paleotropical 7.03 (95% CI: 4.77
      9.28); and African paleotropical 7.05 (95% CI: 1.12-23.58). The difference to the
      autochthonous population was greatest in immigrants of neotropical origin
      (standardised rate ratio = 2.07 (95% CI: 1.61-2.64) or 4.5 excess cases per 1,000
      inhabitants per year) and Asian paleotropical origin (standardised rate ratio =
      3.24 (95% CI: 2.47-4.11) or 9.6 excess cases per 1,000 inhabitants per year).
      Biogeographical origin may therefore account for the vulnerability of certain
      immigrant populations to varicella, in particular those from Asian paleotropical
      (Indostan and Southeast Asia) and neotropical (South America and the Caribbean)
      ecosystems. Vaccination of immigrants at high risk (fertile women, healthcare
      workers) could be recommendable.

PMID- 19761737
TI  - Multidrug-resistant Neisseria gonorrhoeae with reduced cefotaxime susceptibility
      is increasingly common in men who have sex with men, Amsterdam, the Netherlands.
AB  - Antimicrobial resistance is an increasing problem in Neisseria gonorrhoeae (NG)
      treatment. Presently, third-generation parenteral cephalosporins, like
      ceftriaxone and cefotaxime, are the first option. Resistance to oral, but not to
      parenteral, third-generation cephalosporins has been reported previously. We
      analysed the microbial susceptibility (as minimum inhibitory concentration - MIC)
      of NG cultures obtained from high-risk visitors of the largest Dutch outpatient
      clinic for sexually transmitted infections (STI) in Amsterdam, the Netherlands.
      Among 1,596 visitors, we identified 102 patients with at least one NG isolate
      with reduced susceptibility to cefotaxime (0.125 microg/ml < MIC < or = 0.5
      microg/ml). The percentage of NG isolates with reduced susceptibility to
      cefotaxime rose from 4.8% in 2006 to 12.1% in 2008 (chi2 17.5, p<0.001). With
      multivariate logistic regression, being a man who has sex with men (MSM) was
      significantly associated with reduced susceptibility to cefotaxime (p<0.001).
      Compared to susceptible NG isolates, those with decreased susceptiblity to
      cefotaxime were more often resistant also to penicillin (16.5% vs. 43.3%),
      tetracycline (21.5% vs. 68.9%) and ciprofloxacin (44.4% vs. 90.0%, all p<0.001).
      The increased prevalence of NG strains with reduced susceptibility to cefotaxime
      among MSM may herald resistance to third-generation parenteral cephalosporins. A
      considerable proportion of these strains show resistance to multiple antibiotics
      which could limit future NG treatment options.

PMID- 19761738
TI  - Economic consequences to society of pandemic H1N1 influenza 2009 - preliminary
      results for Sweden.
AB  - Experiments using a microsimulation platform show that vaccination against
      pandemic H1N1 influenza is highly cost-effective. Swedish society may reduce the
      costs of pandemic by about SEK 2.5 billion (approximately EUR 250 million) if at
      least 60 per cent of the population is vaccinated, even if costs related to death
      cases are excluded. The cost reduction primarily results from reduced
      absenteeism. These results are preliminary and based on comprehensive assumptions
      about the infectiousness and morbidity of the pandemic, which are uncertain in
      the current situation.

PMID- 19761739
TI  - Sub-optimal hand sanitiser usage in a hospital entrance during an influenza
      pandemic, New Zealand, August 2009.
AB  - The hand hygiene behaviours of the public in response to the current H1N1
      influenza pandemic 2009 (or other pandemics) have not previously been described.
      An observational study was undertaken to examine hand hygiene behaviours by
      people passing a hand sanitiser station in the foyer of a public hospital in New
      Zealand in August 2009. Of the 2,941 subjects observed, 449 (18.0%, 95%
      confidence interval: 16.6, 19.6) used the hand sanitiser. This is a far from
      optimal result in response to the health promotion initiatives in the setting of
      a pandemic. These findings suggest the need for more effective health promotion
      of hand hygiene and also provide baseline measurements for future evaluation of
      hygiene practices.

PMID- 19761740
TI  - [Reengineering health procedures].

PMID- 19761741
TI  - [Strategies for improvement using the continuous evaluation of a protocol:
      afebrile headache in paediatrics].

PMID- 19761742
TI  - [Health care professional view on biomedical research].
AB  - Biomedical research is a necessary subject and enjoys social prestige. AIMS: To
      ascertain the views and expectations of health care professionals on research,
      analysing the influence of their academic training and professional level. DESIGN
      AND METHODS: An anonymous questionnaire was distributed to physicians and
      qualified nurses working in a, tertiary hospital, seven primary care centres and
      two nursing homes (health care centres for the elderly). RESULTS: Cronbach's
      coefficient alpha=0.817. Response rate: 64% (432 out of 682 questionnaires
      distributed). Women: 71%. Mean age: 37 years. Mean years involved in health care:
      14 years. 79% of people considered research as a part of their job, although in
      practice only 43% were doing it. Overall participation in activities was:
      Conferences (71%), education (42%), publications (34%) and ongoing projects
      (17%). Physicians dedicated more off duty time (37%) to research than qualified
      nurses (CI95%: 28 to 46%). The majority of physicians having their doctoral
      thesis would like to carry out research activities, and 84% did so in their free
      time and 74% had active research projects in progress. They identified physician
      workload as the main factor that impedes performing research. Proposals to
      increase research activities were focused on improving resources. CONCLUSIONS:
      The majority of health care professionals expressed a great motivation. The
      perception of research varies depending upon professional qualification.
      Physicians having their doctoral thesis were more involved and had a different
      perception of research, being more critical about available resources. Overall
      research perception was more positive among those with less academic training, as
      well as among those centres with less research activities.

PMID- 19761743
TI  - [How to identify adverse events in emergency services? A guide agreed for the
      screening].
AB  - OBJECTIVE: Since a third of adverse events (AE) occur outside hospital, the
      Emergency Services are a suitable place to look at their incidence. We considered
      designing a screening guide, adapted to the conditions of the emergency services,
      to identify AE. MATERIAL AND METHODS: A qualitative technique was applied
      (nominal group) in which 14 professionals participated. They analysed which
      factors of intrinsic risk, extrinsic risk, and alert conditions, were suitable
      for a screening guide of AE in emergency services. The session was chaired by a
      specialist in these types of techniques. RESULTS: Consensus was high in that the
      most frequent AE in emergencies were those related to medicines, diagnostic tests
      and with the correct identification of the reason for emergency. With respect to
      screening guide, the group proposed adding alcohol abuse, patient social
      problems, cognitive deterioration, basal autonomy and disability. In relation to
      extrinsic risk factors, they pointed to the need of including defibrillation,
      spinal tap or drainage implantation. With respect to the alert conditions form,
      the professionals agreed in that all the criteria seemed correct and suitable,
      except for that related to damage relation childbirth or amniocentesis.
      CONCLUSIONS: By using this technique we have managed to validate materials
      already recognized, and widely used in our country. The screening guide was
      considered useful, with slight modifications in some risk factors and alert
      conditions. The professionals agreed that the MRF2 modular questionnaire is
      appropriate for the characterisation of AE in emergencies.

PMID- 19761744
TI  - [Reflections about of outsourcing of magnetic resonance and the case of the
      Community of Valencia].

PMID- 19761745
TI  - [Comparison of two methods for detecting possible adverse events in hospitalised
      patients].

PMID- 19761746
TI  - [A web information system for enhancing management and improving special care
      services provided to dependent persons].
AB  - OBJECTIVE: Ensuring the quality of services provided in centres where dependent
      persons are seen by specialist services, by improving and enhancing how
      information -salary, control of tasks, patients' records, etc.- is shared between
      staff and carers. A web information system has been developed and experimentally
      deployed to accomplish this. MATERIAL AND METHODS: The accuracy of the system was
      evaluated by assessing how confident the employees were with it rather than
      relying on statistical data. It was experimentally deployed since January 2009 in
      Asociacion de Personas con Discapacidad "El Saliente" that manages several day
      centres in Almeria, for dependent persons over 65 years old, particularly those
      affected by Alzheimer' disease. Incidence data was collected during the
      experimental period. RESULTS: A total of 84% of the employees thought that the
      system helped to manage documents, administrative duties, etc., and 92.4% said
      they could attend to really important tasks because the system was responsible
      for alerting them of every task, such as medication timetables, checking all
      patients were present (to prevent an Alzheimer affected person leaving the
      centre) etc. During this period the incidences reported were reduced by about a
      30%, although data is still partially representative. CONCLUSIONS: As the life
      expectancy of the population gets longer, these centres will increase. Providing
      systems such as the one presented here would be of great help for administrative
      duties (sensitive data protection...) as well as ensuring high quality care and
      attention.

PMID- 19761747
TI  - Approaches to measuring the activities of protein arginine N-methyltransferases.

PMID- 19761748
TI  - HPLC and mass spectrometry analysis of dolichol-phosphates at the cell culture
      scale.
AB  - Dolichols (Dol) are polyprenol lipids that are essential structural components of
      eukaryotic membranes. In addition, the phosphorylated derivatives of Dol function
      as lipid anchors of mono- and oligosaccharide precursors involved in protein
      glycosylation. The biological importance of Dol phosphates (Dol-P) is illustrated
      by the severe outcome of human disorders linked to Dol biosynthetic defects, such
      as Dol-kinase deficiency. For characterization of inherited human diseases and
      evaluation of therapeutic trials, cultured cells often serve as a sole possible
      source for experimentation. Limited amounts of cell culture material render the
      quantitative analysis of Dol a challenging task. Here, we present HPLC- and mass
      spectrometry-based approaches to analyze and quantitate Dol-P from cultured human
      cells. The composition of naturally occurring Dol-P and the saturation state of
      the alpha-isoprene units was identified by negative-ion electrospray ionization
      mass spectrometry. Furthermore, fluorescently labeled Dol-P were separated by
      HPLC and quantified by comparison to known amounts of the internal standard
      polyprenol-P. The effect of pravastatin, a 3-hydroxy-3-methyl-glutaryl coenzyme-A
      reductase inhibitor, on the formation of Dol-P in HeLa cells was investigated. As
      expected, this treatment led to a decrease of Dol-P down to 35% of normal levels.

PMID- 19761749
TI  - Attomole DNA detection assay via rolling circle amplification and single molecule
      detection.
AB  - A bead-based assay was developed for highly sensitive single molecule DNA
      detection. Rolling circle amplification (RCA), an isothermal amplification
      technique that creates tandem repeated sequences, was used in combination with a
      fluorescent complementary DNA to create dense clusters of fluorescence. These
      clusters, each corresponding to a single target molecule, can be detected
      unambiguously due to their high signal/noise ratios. The limit of detection of
      this assay is approximately 1 amol. This simple single molecule assay allows high
      detection sensitivity without the use of complex equipment.

PMID- 19761750
TI  - Efficient readout of posttranslational codes on the 50-residue tail of histone H3
      by high-resolution MS/MS.
AB  - Histone modifications are highly linked to DNA methylation and together they
      exert epigenetic control over many activities in the cell including gene
      transcription. Using a streamlined mass spectrometric approach to determine
      changes in modification states in the first 50 residues of histone H3, we found a
      decrease in the global methylation states of H3.1 at Lys 9, Lys 14, and Lys 27
      after inhibition of DNA methyltransferases by 5-aza-2'-deoxycytidine. Collisional
      ion dissociation methods proved adequate to determine site-specific H3
      posttranslational modifications (PTMs) because ample backbone bonds are cleaved
      between each modification site and PTMs were stable to MS/MS using threshold
      fragmentation in a linear ion trap (LTQ). Our assay allows for a quick profiling
      and site-specific interrogation of modification states on the first 50 residues
      of H3 and is directly applicable to H3.1, H3.2, or H3.3 using most OrbiTrap, FT
      ICR, or TOF mass spectrometers.

PMID- 19761751
TI  - Effect of the P700 pre-oxidation and point mutations near A(0) on the
      reversibility of the primary charge separation in Photosystem I from
      Chlamydomonas reinhardtii.
AB  - Time-resolved fluorescence studies with a 3-ps temporal resolution were performed
      in order to: (1) test the recent model of the reversible primary charge
      separation in Photosystem I (Muller et al., 2003; Holwzwarth et al., 2005, 2006),
      and (2) to reconcile this model with a mechanism of excitation energy quenching
      by closed Photosystem I (with P700 pre-oxidized to P700+). For these purposes, we
      performed experiments using Photosystem I core samples isolated from
      Chlamydomonas reinhardtii wild type, and two mutants in which the methionine
      axial ligand to primary electron acceptor, A(0), has been change to either
      histidine or serine. The temporal evolution of fluorescence spectra was recorded
      for each preparation under conditions where the "primary electron donor," P700,
      was either neutral or chemically pre-oxidized to P700+. For all the preparations
      under study, and under neutral and oxidizing conditions, we observed
      multiexponential fluorescence decay with the major phases of approximately 7 ps
      and approximately 25 ps. The relative amplitudes and, to a minor extent the
      lifetimes, of these two phases were modulated by the redox state of P700 and by
      the mutations near A(0): both pre-oxidation of P700 and mutations caused slight
      deceleration of the excited state decay. These results are consistent with a
      model in which P700 is not the primary electron donor, but rather a secondary
      electron donor, with the primary charge separation event occurring between the
      accessory chlorophyll, A, and A(0). We assign the faster phase to the
      equilibration process between the excited state of the antenna/reaction center
      ensemble and the primary radical pair, and the slower phase to the secondary
      electron transfer reaction. The pre-oxidation of P700 shifts the equilibrium
      between the excited state and the primary radical pair towards the excited state.
      This shift is proposed to be induced by the presence of the positive charge on
      P700+. The same charge is proposed to be responsible for the fast A+A(0)(-)-
      >AA(0) charge recombination to the ground state and, in consequence, excitation
      quenching in closed reaction centers. Mutations of the A(0) axial ligand shift
      the equilibrium in the same direction as pre-oxidation of P700 due to the up
      shift of the free energy level of the state A+A(0)(-).

PMID- 19761752
TI  - Mitochondrial DNA mutations and human disease.
AB  - Mitochondrial disorders are a group of clinically heterogeneous diseases,
      commonly defined by a lack of cellular energy due to oxidative phosphorylation
      (OXPHOS) defects. Since the identification of the first human pathological
      mitochondrial DNA (mtDNA) mutations in 1988, significant efforts have been spent
      in cataloguing the vast array of causative genetic defects of these disorders.
      Currently, more than 250 pathogenic mtDNA mutations have been identified. An ever
      increasing number of nuclear DNA mutations are also being reported as the
      majority of proteins involved in mitochondrial metabolism and maintenance are
      nuclear-encoded. Understanding the phenotypic diversity and elucidating the
      molecular mechanisms at the basis of these diseases has however proved
      challenging. Progress has been hampered by the peculiar features of mitochondrial
      genetics, an inability to manipulate the mitochondrial genome, and difficulties
      in obtaining suitable models of disease. In this review, we will first outline
      the unique features of mitochondrial genetics before detailing the diseases and
      their genetic causes, focusing specifically on primary mtDNA genetic defects. The
      functional consequences of mtDNA mutations that have been characterised to date
      will also be discussed, along with current and potential future diagnostic and
      therapeutic advances.

PMID- 19761753
TI  - Localization of Pcb antenna complexes in the photosynthetic prokaryote
      Prochlorothrix hollandica.
AB  - The freshwater filamentous green oxyphotobacterium Prochlorothrix hollandica is
      an unusual oxygenic photoautotrophic cyanobacterium differing from most of the
      others by the presence of light-harvesting Pcb antenna binding both chlorophylls
      a and b and by the absence of phycobilins. The pigment-protein complexes of P.
      hollandica SAG 10.89 (CCAP 1490/1) were isolated from dodecylmaltoside
      solubilized thylakoid membranes on sucrose density gradient and characterized by
      biochemical, spectroscopic and immunoblotting methods. The Pcb antennae
      production is suppressed by high light conditions (>200 mumol photons m(-2) s(
      1)) in P. hollandica. PcbC protein was found either in higher oligomeric states
      or coupled to PS I (forming antenna rings around PS I). PcbA and PcbB are most
      probably only very loosely bound to photosystems; we assume that these pigment
      protein complexes function as low light-induced mobile antennae. Further, we have
      detected alpha-carotene in substantial quantities in P. hollandica thylakoid
      membranes, indicating the presence of chloroplast-like carotenoid synthetic
      pathway which is not present in common cyanobacteria.

PMID- 19761754
TI  - Structure assembly of Bcl-x(L) through alpha5-alpha5 and alpha6-alpha6 interhelix
      interactions in lipid membranes.
AB  - Lipid bilayer membrane is the main site where Bcl-x(L) executes its anti
      apoptotic function. Here we used site-directed mutagenesis and cysteine-directed
      cross-linking to trap the structure of Bcl-x(L) upon membrane insertion. Cys151
      on alpha5-helix and Asn185 on alpha6-helix of two neighboring Bcl-x(L) are found
      in close positions, respectively. The FRET based binding assay indicated that the
      BH3-peptide binding pocket in Bcl-x(L) is disrupted after its membrane insertion.
      Co-immunoprecipitation experiments showed that the membrane-bound Bcl-x(L)
      sequestered tBid by direct interaction at physiological pH. If Bcl-x(L) behaves
      similarly at low pH as it does at physiological pH, the membrane-bound Bcl-x(L)
      should bind to tBid through protein regions other than the BH3 domain of tBid and
      the hydrophobic pocket of Bcl-x(L). Previously, a crystallography study
      demonstrated that Bcl-x(L) formed homodimers through domain swapping in water,
      where Cys151 and Asn185 of two monomeric subunits are far apart from each other
      and the BH3-peptide binding pocket is intact. Our results indicated that Bcl-x(L)
      dimer trapped by cross-linking in lipids is distinct from the domain swapped
      dimer, suggesting that Bcl-x(L) transits through a structural change from the
      water-soluble state to the membrane-bound state and there are multiple
      possibilities for structural reorganization of Bcl-x(L) protein.

PMID- 19761755
TI  - Insights into the effect of detergents on the full-length rhomboid protease from
      Pseudomonas aeruginosa and its cytosolic domain.
AB  - Rhomboids comprise a family of intramembrane serine proteases that catalyze the
      cleavage of transmembrane segments within the lipid membrane to achieve a wide
      range of biological functions. A subset of bacterial rhomboids possesses an N
      terminal cytosolic domain that appears to enhance proteolytic activity via an
      unknown mechanism. Structural analysis of a full-length rhomboid would provide
      new insights into this mechanism, an objective that solution NMR has the
      potential to realize. For this purpose we purified the rhomboid from Pseudomonas
      aeruginosa in a range of membrane-mimetic media, evaluated its functional status
      in vitro and investigated the NMR spectroscopic properties of these samples. In
      general, NMR signals could only be observed from the cytosolic domain, and only
      in detergents that did not support rhomboid activity. In contrast, media that
      supported rhomboid function did not show these resonances, suggesting an
      association between the cytosolic domain and the protein-detergent complex.
      Investigations into the ability of the isolated cytosolic domain to bind
      detergent micelles revealed a denaturing interaction, whereas no interaction
      occurred with micelles that supported rhomboid activity. The cytosolic domain
      also did not show any tendency to interact with lipid bilayers found in small
      bicelles or vesicles made from Escherichia coli phospholipid extracts. Based on
      these data we propose that the cytosolic domain does not interact with the lipid
      membrane, but instead enhances rhomboid activity through interactions with some
      other part of the rhomboid, such as the catalytic core domain.

PMID- 19761756
TI  - Physical properties of the lipid bilayer membrane made of cortical and nuclear
      bovine lens lipids: EPR spin-labeling studies.
AB  - The physical properties of membranes derived from the total lipids extracted from
      the lens cortex and nucleus of a 2-year-old cow were investigated using EPR spin
      labeling methods. Conventional EPR spectra and saturation-recovery curves show
      that spin labels detect a single homogenous environment in membranes made from
      cortical lipids. Properties of these membranes are very similar to those reported
      by us for membranes made of the total lipid extract of 6-month-old calf lenses
      (J. Widomska, M. Raguz, J. Dillon, E. R. Gaillard, W. K. Subczynski, Biochim.
      Biophys. Acta 1768 (2007) 1454-1465). However, in membranes made from nuclear
      lipids, two domains were detected by the EPR discrimination by oxygen transport
      method using the cholesterol analogue spin label and were assigned to the bulk
      phospholipid-cholesterol domain (PCD) and the immiscible cholesterol crystalline
      domain (CCD), respectively. Profiles of the order parameter, hydrophobicity, and
      the oxygen transport parameter are practically identical in the bulk PCD when
      measured for either the cortical or nuclear lipid membranes. In both membranes,
      lipids in the bulk PCD are strongly immobilized at all depths. Hydrophobicity and
      oxygen transport parameter profiles have a rectangular shape with an abrupt
      change between the C9 and C10 positions, which is approximately where the steroid
      ring structure of cholesterol reaches into the membrane. The permeability
      coefficient for oxygen, estimated at 35 degrees C, across the bulk PCD in both
      membranes is slightly lower than across the water layer of the same thickness.
      However, the evaluated upper limit of the permeability coefficient for oxygen
      across the CCD (34.4 cm/s) is significantly lower than across the water layer of
      the same thickness (85.9 cm/s), indicating that the CCD can significantly reduce
      oxygen transport in the lens nucleus.

PMID- 19761757
TI  - The role of the Ca2+ binding ligand Asn879 in the function of the plasma membrane
      Ca2+ pump.
AB  - Asn879 in the transmembrane segment M6 of the plasma membrane Ca(2+) pump (PMCA
      human isoform 4xb) has been proposed to coordinate Ca(2+) at the transport site
      through its carboxylate. This idea agrees with the fact that this Asn is
      conserved in other Ca(2+)-ATPases but is replaced by Asp, Glu, and other residues
      in closely related 2P-type ATPases of different ionic specificity. Previous
      mutagenesis studies have shown that the substitution of Ala for Asn abolishes the
      activity of the enzyme (Adebayo et al., 1995; Guerini et al., 1996). We have
      constructed a mutant PMCA in which the Asn879 was substituted by Asp. The mutant
      protein was expressed in Saccharomyces cerevisiae, solubilized and purified by
      calmodulin affinity chromatography. The Asn879Asp PMCA mutant exhibited about 30%
      of the wild type Ca(2+)-dependent ATPase activity and only a minor reduction of
      the apparent affinity for Ca(2+). The decrease in the Ca(2+)-ATPase of the mutant
      enzyme was in parallel with the reduction in the amount of phosphoenzyme formed
      from Ca(2+) plus ATP. Noteworthy, the mutation nearly eliminated the ability of
      the enzyme to hydrolyze pNPP which is maximal in the absence of Ca(2+) revealing
      a major effect of the mutation on the Ca(2+)-independent reactions of the
      transport cycle. At a pH low enough to protonate the Asp carboxylate the pNPPase
      activity of Asn879Asp increased, suggesting that the binding of protons to Asn879
      is essential for the activities catalyzed by E(2)-like forms of the enzyme.

PMID- 19761759
TI  - A calorimetric and spectroscopic comparison of the effects of ergosterol and
      cholesterol on the thermotropic phase behavior and organization of
      dipalmitoylphosphatidylcholine bilayer membranes.
AB  - We performed comparative DSC and FTIR spectroscopic measurements of the effects
      of cholesterol (Chol) and ergosterol (Erg) on the thermotropic phase behavior and
      organization of DPPC bilayers. Ergosterol is the major sterol in the biological
      membranes of yeasts, fungi and many protozoa. It differs from Chol in having two
      additional double bonds, one in the steroid nucleus at C7-8 and another in the
      alkyl chain at C22-23. Erg also has an additional methyl group in the alkyl chain
      at C24. Our DSC studies indicate that the incorporation of Erg is more effective
      than Chol is in reducing the enthalpy of the pretransition. At lower
      concentrations Erg is also more effective than Chol in reducing the enthalpies of
      both the sharp and broad components of main phase transition. However, at sterol
      concentrations from 30 to 50 mol%, Erg is generally less effective at reducing
      the enthalpy of the broad components and does not completely abolish the
      cooperative hydrocarbon chain-melting phase transition at 50 mol%, as does Chol.
      Nevertheless, in this higher ergosterol concentration range, there is no evidence
      of the formation of ergosterol crystallites. Our FTIR spectroscopic studies
      demonstrate that Erg incorporation produces a similar ordering of liquid
      crystalline DPPC bilayers as does Chol, but an increased degree of hydrogen
      bonding of the fatty acyl carbonyl groups in the glycerol backbone region of the
      DPPC bilayer. These and other results indicate that Erg is less miscible in DPPC
      bilayers at higher concentrations than is Chol. Finally, we provide a tentative
      molecular explanation for the comparative experimental and computation results
      obtained for Erg and Chol in phospholipid bilayers, emphasizing the dynamic
      conformational differences between these two sterols.

PMID- 19761758
TI  - Effects of PKA phosphorylation on the conformation of the Na,K-ATPase regulatory
      protein FXYD1.
AB  - FXYD1 (phospholemman) is a member of an evolutionarily conserved family of
      membrane proteins that regulate the function of the Na,K-ATPase enzyme complex in
      specific tissues and specific physiological states. In heart and skeletal muscle
      sarcolemma, FXYD1 is also the principal substrate of hormone-regulated
      phosphorylation by c-AMP dependent protein kinase A and by protein kinase C,
      which phosphorylate the protein at conserved Ser residues in its cytoplasmic
      domain, altering its Na,K-ATPase regulatory activity. FXYD1 adopts an L-shaped
      alpha-helical structure with the transmembrane helix loosely connected to a
      cytoplasmic amphipathic helix that rests on the membrane surface. In this paper
      we describe NMR experiments showing that neither PKA phosphorylation at Ser68 nor
      the physiologically relevant phosphorylation mimicking mutation Ser68Asp induces
      major changes in the protein conformation. The results, viewed in light of a
      model of FXYD1 associated with the Na,K-ATPase alpha and beta subunits, indicate
      that the effects of phosphorylation on the Na,K-ATPase regulatory activity of
      FXYD1 could be due primarily to changes in electrostatic potential near the
      membrane surface and near the Na(+)/K(+) ion binding site of the Na,K-ATPase
      alpha subunit.

PMID- 19761760
TI  - The dsRNA-mimetic poly (I:C) and IL-18 synergize for IFNgamma and TNFalpha
      expression.
AB  - Interleukin (IL)-18 bioactivity and dsRNA sensing by receptors of innate immunity
      are key components of anti-viral host defense. Despite extensive data on signal
      transduction activated by both pathways knowledge on cross-communication is
      incomplete. By using human PBMC and predendritic KG1 cells, as prototypic IL-18
      responsive cellular models, we sought to assess cytokine production under the
      influence of IL-18 and the dsRNA-mimetic poly (I:C). Here, we report on potent
      synergy between both mediators concerning pro-inflammatory IFNgamma and TNFalpha
      production. KG1 data revealed that synergistic induction likely relied on TLR3
      and was associated with prolonged/increased activation of NF-kappaB, as detected
      by IkappaB analysis and luciferase reporter assays, respectively. Moreover,
      extended activation of JNK was mediated by IL-18/poly (I:C). Although vital for
      innate immunity, overwhelming induction of inflammatory cytokines during viral
      infections poses the threat of serious collateral tissue damage. The stunning
      synergism inherent to IL-18/dsRNA-induced TNFalpha/IFNgamma detected herein may
      contribute to this pathological phenomenon.

PMID- 19761761
TI  - The impact of adenosine and an A2A adenosine receptor agonist on the ACh-induced
      increase in intracellular calcium of the glomus cells of the cat carotid body.
AB  - The carotid body (CB) is a polymodal chemosensor of arterial blood located next
      to the internal carotid artery. The basic chemosensing unit is composed of the
      neurotransmitter (NT)-containing glomus cells (GCs) and the sensory afferent
      fibers synapsing onto the GCs. Nicotinic and muscarinic receptors have been found
      on both the sensory afferent fibers and on the GCs. Neural output from the CB
      (CBNO) increases when arterial blood perfusing it is hypoxic, hypoglycemic,
      hypercapnic, or acidic. The increased CBNO due to GC release of excitatory NTs
      must be preceded by an entrance of calcium into the GCs. With repeated release of
      ACh from the GCs, cholinergic receptors could become desensitized, particularly
      nicotinic receptors which function as calcium channels. The purpose of the
      present study was to see if adenosine (ADO), known to alter receptor
      sensitivities, could attenuate or eliminate any desensitization of the nicotinic
      receptors occurring during the repeated application of ACh. Cat CBs were
      harvested with techniques approved by the University's Animal Care/Use Committee.
      The GCs were cultured and prepared for detecting [Ca(++)](i) with standard
      techniques. Repeated application of ACh produced a progressively decreasing
      increase in [Ca(++)](i). With the use of ADO or an A2(A) ADO receptor agonist the
      decrease was avoided. Though ADO also increased GC [Ca(++)](i), the sum of ADO
      increase and ACh increase, when superfused separately, was less than the increase
      when they were both included in the same superfusion. This suggested the possible
      involvement of a new path in the action. Potential mechanisms to explain the
      phenomena are discussed.

PMID- 19761762
TI  - Cognitive dysfunction induced by chronic cerebral hypoperfusion in a rat model
      associated with arteriovenous malformations.
AB  - The relationship between chronic cerebral hypoperfusion and cognitive function
      has not been completely delineated. In the present studies, we developed an
      experimental model associated with arteriovenous malformation to investigate the
      effects of chronic cerebral hypoperfusion on cognitive function and
      neuropathological changes. The rat model was established by creating a fistula
      through an end-to-side anastomosis between the right distal external jugular vein
      and the ipsilateral common carotid artery, followed by ligation of the left vein
      draining the transverse sinus and bilateral external carotid arteries. Age
      matched rats comprised a control group. Three months after surgery, cognitive
      functions were evaluated by the Morris water maze and hippocampal long-term
      potentiation (LTP). Neuropathological changes were examined using light and
      electron microscopic techniques. We found that both learning capacity and spatial
      memory were significantly impaired in rats with chronic cerebral hypoperfusion
      concomitant with LTP inhibition and neurodegeneration in the hippocampal CA1
      region of model rats compared with control rats. In addition, model rats showed a
      decrease at the protein level of cyclic AMP response element binding (CREB)
      phosphorylation in hippocampal tissues. Therefore, cognitive impairment caused by
      chronic cerebral hypoperfusion associated with arteriovenous malformations may be
      partially explained by the neurodegeneration and reduction of CREB
      phosphorylation in rat hippocampus.

PMID- 19761763
TI  - Regulation of Hh signal transduction as Drosophila eye differentiation
      progresses.
AB  - Differentiation of the Drosophila retina occurs as a morphogenetic furrow sweeps
      anteriorly across the eye imaginal disc, driven by Hedgehog secretion from
      photoreceptor precursors differentiating behind the furrow. A BTB protein,
      Roadkill, is expressed posterior to the furrow and targets the Hedgehog signal
      transduction component Cubitus interruptus for degradation by Cullin-3 and the
      proteosome. Clonal analysis and conditional mutant studies establish that
      roadkill transcription is activated by the EGF receptor and Ras pathway in most
      differentiating retinal cells, and by both EGF receptor/Ras and by Hedgehog
      signaling in cells that remain unspecified. These findings outline a circuit by
      which Hedgehog signal transduction is modified as Hedgehog signaling initiates
      retinal differentiation. A model is presented for regulation of the Cullin-3 and
      Cullin-1 pathways that modifies Hedgehog signaling as the morphogenetic furrow
      moves and the responses of retinal cells change.

PMID- 19761764
TI  - Association between vascular endothelial growth factor gene polymorphisms and age
      related macular degeneration in a Polish population.
AB  - The pathogenesis of age-related macular degeneration (AMD) is thought to be
      determined by an array of environmental and genetic factors. The association of
      increased expression of vascular endothelial growth factor (VEGF) with AMD,
      especially the wet form of AMD, was reported in several studies. The VEGF gene is
      highly polymorphic and some of its polymorphisms may affect its expression. In
      our work, we searched for an association between the -460C> (rs833061) and 
      634G>C (rs2010963) polymorphisms of the VEGF gene and the occurrence of AMD and
      its dry and wet forms. We have chosen these polymorphisms because they were shown
      to be significant in other studies and we previously showed their association
      with diabetic retinopathy. A total of 401 individuals were enrolled in this
      study: 136 controls, and 88 patients with dry and 177 with wet AMD. The
      polymorphisms were determined with DNA from peripheral blood lymphocytes by
      allele-specific and restriction fragment length polymorphism polymerase chain
      reaction. The significance of the polymorphisms was assessed by multiple logistic
      regression, producing odds ratios (ORs) and 95% confidence intervals (CIs). We
      observed a weak association (OR 2.90) between AMD occurrence and the C/T genotype
      of the -460C>T polymorphism. An association (OR 3.77) between the C/T genotype of
      the -460C>T polymorphism and the occurrence of dry AMD was observed. The T/T
      genotype considerably lowered the risk of dry AMD (OR 0.19). Dry AMD was
      associated with the C/C genotype of the -634G>C polymorphism (OR 3.68). Another
      weak association (OR 2.63) was found between the C/T genotype of the -460C>T
      polymorphism and the occurrence of wet AMD. The occurrence of AMD was correlated
      with the presence of the combined C/T-G/G genotype of both polymorphisms (OR
      2.41), whereas the T/T-G/G and T/T-G/C genotypes exerted a protective effect
      against the disease (OR 0.22 and 0.48, respectively). The presence of the C/T-G/G
      and C/T-C/C combined genotypes increased the risk of dry AMD (OR 2.08 and 3.77,
      respectively), whereas the presence of the T/T-G/G and T/T-G/C genotypes
      decreased the risk (OR 0.15 and 0.28, respectively). In the wet form of AMD, the
      combined genotype C/T-G/G slightly favored the disease (OR 2.61) and the T/T-G/G
      genotype had a protective effect (OR 0.25). Analysis of haplotypes of both
      polymorphisms yielded similar results for AMD in general as well as for the dry
      and wet forms of the disease: the CG haplotype favored both forms of AMD, whereas
      the TG haplotype protected against both forms of AMD. The results obtained
      indicate that the -460C>T and -634G>C polymorphisms of the VEGF gene may be
      associated with the dry and wet forms of AMD in a Polish population.

PMID- 19761765
TI  - Localization of vascular adhesion protein-1 (VAP-1) in the human eye.
AB  - Recently we showed a critical role for Vascular Adhesion Protein-1 (VAP-1) in
      rodents during acute ocular inflammation, angiogenesis, and diabetic retinal
      leukostasis. However, the expression of VAP-1 in the human eye is unknown. VAP-1
      localization was therefore investigated by immunohistochemistry. Five micrometer
      thick sections were generated from human ocular tissues embedded in paraffin.
      Sections were incubated overnight with primary mAbs against VAP-1 (5 microg/ml),
      smooth muscle actin (1 microg/ml), CD31 or isotype-matched IgG at 4 degrees C.
      Subsequently, a secondary mAb was used for 30 min at room temperature, followed
      by Dako Envision + HRP (AEC) System for signal detection. The stained sections
      were examined using light microscopy and the signal intensity was quantified by
      two evaluators and graded into 4 discrete categories. In all examined ocular
      tissues, VAP-1 staining was confined to the vasculature. VAP-1 labeling showed
      the highest intensity in both arteries and veins of neuronal tissues: retina and
      optic nerve, and the lowest intensity in the iris vasculature (p < 0.05). Scleral
      and choroidal vessels showed moderate staining for VAP-1. VAP-1 intensity was
      significantly higher in the arteries compared to veins (p < 0.05). Furthermore,
      VAP-1 staining in arteries colocalized with both CD31 and smooth muscle actin (sm
      actin) staining, suggesting expression of VAP-1 in endothelial cells, smooth
      muscle cells or potentially pericytes. In conclusion, immunohistochemistry
      reveals constitutive expression of VAP-1 in human ocular tissues. VAP-1
      expression is nearly exclusive to the vasculature with arteries showing
      significantly higher expression than veins. Furthermore, VAP-1 expression in the
      ocular vasculature is heterogeneous, with the vessels of the optic nerve and the
      retina showing highest expressions. These results characterize VAP-1 expression
      in human ocular tissues.

PMID- 19761766
TI  - A distinct structural region of the prokaryotic ubiquitin-like protein (Pup) is
      recognized by the N-terminal domain of the proteasomal ATPase Mpa.
AB  - The mycobacterial ubiquitin-like protein Pup is coupled to proteins, thereby
      rendering them as substrates for proteasome-mediated degradation. The Pup-tagged
      proteins are recruited by the proteasomal ATPase Mpa (also called ARC). Using a
      combination of biochemical and NMR methods, we characterize the structural
      determinants of Pup and its interaction with Mpa, demonstrating that Pup adopts a
      range of extended conformations with a short helical stretch in its C-terminal
      portion. We show that the N-terminal coiled-coil domain of Mpa makes extensive
      contacts along the central region of Pup leaving its N-terminus unconstrained and
      available for other functional interactions.

PMID- 19761767
TI  - Cell adaptation to activated FGFR3 includes Sprouty4 up regulation to inhibit the
      receptor-mediated ERKs activation from the endoplasmic reticulum.
AB  - The kinase activity of the thanatophoric dysplasia type II-fibroblast growth
      factor receptor 3 mutant (TDII-FGFR3) hampers its maturation. As a consequence,
      the immature receptor activates extracellular regulated kinases (ERKs) from the
      endoplasmic reticulum (ER), which leads to apoptosis. On the other hand, in
      stable TDII-FGFR3 cells receptor biosynthesis is restored and ERKs are activated
      from the cell surface. To identify potential mediators of cell adaptation to the
      activated receptor we investigated gene products that are differently regulated
      in TDII and wild-type FGFR3 cells. cDNA representational difference analysis
      reveals Sprouty4 up regulation in the TDII-FGFR3 cells. Interestingly, Sprouty4
      inhibits the TDII-FGFR3-mediated ERKs activation from the ER, but fails to
      suppress ERKs activation from cell surface. We conclude that cell adaptation to
      activated FGFR3 include Sprouty4 activity, which silences the premature receptor
      signaling and suppress apoptosis.

PMID- 19761769
TI  - Evolution of the trypanorhynch tapeworms: parasite phylogeny supports independent
      lineages of sharks and rays.
AB  - Trypanorhynch tapeworms (Platyhelminthes: Cestoda) are among the most diverse and
      abundant groups of metazoan parasites of elasmobranchs and are a ubiquitous part
      of the marine food webs that include these apex predators. Here we present a
      comprehensive analysis of their phylogeny, character evolution and host
      associations based on 10years of sampling effort, including representatives of 12
      of 15 and 44 of 66 currently recognized trypanorhynch families and genera,
      respectively. Using a combination of ssrDNA and lsrDNA (Domains 1-3) for 79 and
      80 taxa, respectively, we maintain one-to-one correspondence between molecules
      and morphology by scoring 45 characters from the same specimens used for
      sequencing, and provide museum vouchers for this material. Host associations are
      examined through likelihood-based ancestral character state reconstructions
      (ACSRs) and by estimating dates of divergence using strict and relaxed molecular
      clock models in a Bayesian context. Maximum parsimony and Bayesian inference
      analyses of rDNA produced well-resolved and strongly supported trees in which the
      trypanorhynchs formed two primary lineages and were monophyletic with respect to
      the diphyllidean outgroup taxa. These lineages showed marked differences in their
      rates of divergence which in turn resulted in differing support and stability
      characteristics within the lineages. Mapping of morphological characters onto the
      tree resulting from combined analysis of rDNA showed most traits to be highly
      plastic, including some previously considered of key taxonomic importance such as
      underlying symmetries in tentacular armature. The resulting tree was found to be
      congruent with the most recent morphologically based superfamily designations in
      the order, providing support for four proposed superfamilies, but not for the
      Tentacularioidea and Eutetrarhynchoidea. ACSRs based on the combined analysis of
      rDNA estimated the original hosts of the two primary parasite lineages to be
      alternatively rajiform batoids and carcharhiniform sharks. This fundamental split
      provides independent support for rejecting the notion that rays are derived
      sharks, and thus supports the most recent molecular phylogenies of the
      Neoselachii. Beyond the basal split between shark- and ray-inhabiting lineages,
      no pattern was found to suggest that the trypanorhynchs have closely tracked the
      evolutionary histories of these host lineages, but instead, it appears that host
      switching has been common and that the subsequent evolution of the parasites has
      been ecologically driven primarily through overlap in the niches of their shark
      and ray hosts. Using a relaxed molecular clock model calibrated by means of host
      fossil data, the ray-inhabiting lineage is estimated to have diversified around
      the Jurassic-Cretaceous boundary, whereas the shark-inhabiting lineage is
      estimated to have diversified later, in the Middle Cretaceous. Although the large
      error associated with the estimated divergence dates prevents robust conclusions
      from being drawn, the dates are nevertheless found to be consistent in a relative
      sense with the origins of their major hosts groups. The erection and definition
      of the suborders Trypanobatoida and Trypanoselachoida, for the major clades of
      trypanorhynchs parasitizing primarily rays and sharks, respectively, is proposed
      for the two primary lineages recovered here.

PMID- 19761770
TI  - Development and use of a novel in vitro assay for testing of diphtheria toxoid in
      combination vaccines.
AB  - Testing of diphtheria vaccines for routine lot release relies heavily on the use
      of in vivo potency assays. However, consistency of production is also recognised
      as an important feature of vaccine manufacture, and in vitro assays are superior
      to in vivo assays for providing this information. In adsorbed vaccines, antigen
      and adjuvant are the major components contributing to immunogenicity and are
      therefore critical factors to be evaluated as part of consistency testing. Here
      we describe a simple and sensitive Enzyme Linked Immunosorbent Assay (ELISA)
      which has been developed to quantify diphtheria toxoid antigen in combined
      vaccine products and can also be used to monitor the degree of adsorption. This
      assay can be applied to a variety of multi-component vaccines and is robust,
      specific and highly sensitive, with a limit of quantification of approximately
      0.005 Lf/ml. The antigen assay is an excellent test to characterise vaccines and
      monitor trends in production. For well established vaccines, the antigen assay
      could be used alongside other in vitro methods to provide a more informative
      product profile, with the ultimate aim of reducing the requirement for in vivo
      potency assays and therefore the number of animals required for routine batch
      release testing.

PMID- 19761771
TI  - Characterization of a new insect cell line (NTU-YB) derived from the common grass
      yellow butterfly, Eurema hecabe (Linnaeus) (Pieridae: Lepidoptera) and its
      susceptibility to microsporidia.
AB  - A new lepidopteran cell line, NTU-YB, was derived from pupal tissue of Eurema
      hecabe (Linnaeus) (Pieridae: Lepidoptera). The doubling time of YB cells in TNM
      FH medium supplemented with 8% FBS at 28 degrees C was 26.87h. The chromosome
      numbers of YB cells varied widely from 21 to 196 with a mean of 86. Compared to
      other insect cell lines, the YB cells produced distinct esterase, malate
      dehydrogenase, and lactate dehydrogenase isozyme patterns. Identity of the
      internal transcribed spacer region-I (ITS-I) of YB cells to E. hecabe larvae was
      96% and to Eurema blanda larvae (tissue isolated from head) was 81%. The YB cells
      were permissive to Nosema sp. isolated from E. blanda and the infected YB cells
      showed obvious cytopathic effects after 3weeks post inoculation. The highest
      level of spore production was at 4weeks post inoculation when cells were infected
      with the Nosema isolate, and spore production was 1.34+/-0.9x10(6)spore/ml.
      Ultrastructrual studies showed that YB cells can host in vitro propagation of the
      E. blanda Nosema isolate, and developing stages were observed in the host cell
      nuclei as observed in the natural host, E. blanda. The NTU-YB cell line is also
      susceptible to Nosema bombycis.

PMID- 19761772
TI  - Eicosanoids influence insect susceptibility to nucleopolyhedroviruses.
AB  - Nine pharmaceutical inhibitors of eicosanoid biosynthesis (e.g., bromophenacyl
      bromide, clotrimazole, diclofenamic acid, esculetin, flufenamic acid,
      indomethacin, nimesulide, sulindac, tolfenamic acid) that increased the
      susceptibility of the gypsy moth, Lymantria dispar (L.), to the
      nucleopolyhedrovirus LdMNPV were tested against the beet armyworm Spodoptera
      exigua (Hubner), the corn earworm Helicoverpa zea (Boddie) and the fall armyworm
      Spodoptera frugiperda (J.E. Smith) and their respective NPVs to determine whether
      these compounds also alter the susceptibility of these insects. The
      susceptibility of the beet armyworm was increased by six inhibitors
      (bromophenacyl bromide, clotrimazole, diclofenic acid, esculetin, flufenamic
      acid, nimesulide). The susceptibility of the fall armyworm was increased by seven
      inhibitors, (bromophenacyl bromide, diclofenamic acid, esculetin, indomethacin,
      nimesulide, sulindac, tolfenamic acid), whereas the susceptibility of the corn
      earworm was increased by only one inhibitor (sulindac). The influence of the
      cyclooxygenase inhibitor, indomethacin was expressed in a concentration-related
      manner in beet armyworms. We infer from these findings that eicosanoids,
      including prostaglandins and lipoxygenase products, act in insect anti-viral
      defenses.

PMID- 19761773
TI  - Two complementary enzymes for threonylation of tRNA in crenarchaeota: crystal
      structure of Aeropyrum pernix threonyl-tRNA synthetase lacking a cis-editing
      domain.
AB  - In protein synthesis, threonyl-tRNA synthetase (ThrRS) must recognize threonine
      (Thr) from the 20 kinds of amino acids and the cognate tRNA(Thr) from different
      tRNAs in order to generate Thr-tRNA(Thr). In general, an organism possesses one
      kind of gene corresponding to ThrRS. However, it has been recently found that
      some organisms have two different genes for ThrRS in the genome, suggesting that
      their proteins ThrRS-1 and ThrRS-2 function separately and complement each other
      in the threonylation of tRNA(Thr), one for catalysis and the other for trans
      editing of misacylated Ser-tRNA(Thr). In order to clarify their three-dimensional
      structures, we performed X-ray analyses of two putatively assigned ThrRSs from
      Aeropyrum pernix (ApThrRS-1 and ApThrRS-2). These proteins were overexpressed in
      Escherichia coli, purified, and crystallized. The crystal structure of ApThrRS-1
      has been successfully determined at 2.3 A resolution. ApThrRS-1 is a dimeric
      enzyme composed of two identical subunits, each containing two domains for the
      catalytic reaction and for anticodon binding. The essential editing domain is
      completely missing as expected. These structural features reveal that ThrRS-1
      catalyzes only the aminoacylation of the cognate tRNA, suggesting the necessity
      of the second enzyme ThrRS-2 for trans-editing. Since the N-terminal sequence of
      ApThrRS-2 is similar to the sequence of the editing domain of ThrRS from
      Pyrococcus abyssi, ApThrRS-2 has been expected to catalyze deaminoacylation of a
      misacylated serine moiety at the CCA terminus.

PMID- 19761774
TI  - Kinetics of paused ribosome recycling in Escherichia coli.
AB  - The bacterial tmRNA.SmpB system recycles stalled translation complexes in a
      process termed 'ribosome rescue.' tmRNA.SmpB specifically recognizes ribosomes
      that are paused at or near the 3' end of truncated mRNA; therefore, nucleolytic
      mRNA processing is required before paused ribosomes can be rescued from full
      length transcripts. Here, we examine the recycling of ribosomes paused on both
      full-length and truncated mRNAs. Peptidyl-tRNAs corresponding to each paused
      translation complex were identified, and their turnover kinetics was used to
      estimate the half-lives of paused ribosomes in vivo. Ribosomes were paused at
      stop codons on full-length mRNA using a nascent peptide motif that interferes
      with translation termination and elicits tmRNA.SmpB activity. Peptidyl-tRNA
      turnover from these termination-paused ribosomes was slightly more rapid in
      tmRNA(+) cells (T(1/2)=22+/-2.2 s) than in DeltatmRNA cells (T(1/2)=32+/-1.6 s).
      Overexpression of release factor (RF) 1 greatly accelerated peptidyl-tRNA
      turnover from termination-paused ribosomes in both tmRNA(+) and DeltatmRNA cells,
      whereas other termination factors had little or no effect on recycling. In
      contrast to inefficient translation termination, ribosome recycling from
      truncated transcripts lacking in-frame stop codons was dramatically accelerated
      by tmRNA.SmpB. However, peptidyl-tRNA still turned over from nonstop-paused
      ribosomes at a significant rate (t(1/2)=61+/-7.3 s) in DeltatmRNA cells.
      Overexpression of RF-1, RF-3, and ribosome recycling factor in DeltatmRNA cells
      failed to accelerate ribosome recycling from nonstop mRNA. These results indicate
      that tmRNA.SmpB activity is rate limited by mRNA cleavage, and that RF-3 and
      ribosome recycling factor do not constitute a tmRNA-independent rescue pathway,
      as previously suggested. Peptidyl-tRNA turnover from nonstop-paused ribosomes in
      DeltatmRNA cells suggests the existence of another uncharacterized ribosome
      rescue pathway.

PMID- 19761775
TI  - The role of exon sequences in C complex spliceosome structure.
AB  - Pre-mRNA splicing is catalyzed by a large ribonucleoprotein complex called the
      spliceosome. Previous electron microscopy reconstruction of C complex
      spliceosomes arrested between the two chemical steps of splicing revealed an
      averaged core structure consisting of three primary domains surrounding a central
      cavity. Here we characterize the involvement of pre-mRNA in this structured core
      of C complex by protection mapping. We find that the 3' end of the cleaved 5'
      exon and intron sequences flanking the branched lariat are buried in the complex.
      Upstream regions of the 5' exon and the entire 3' exon, including the mutant 3'
      splice site, are accessible and can be removed by nucleolytic cleavage.
      Furthermore, we show that the second-step active site of the complex, which is
      arrested by a 3' splice site mutation, can accept a normal 3' splice site in
      trans to catalyze exon ligation. Removal of the accessible exon regions alters
      the protein composition of the complex, but the core spliceosome proteins
      associated with the uridine-rich small nuclear ribonucleoproteins U2, U5, and U6
      and the Prp19 complex as well as several other proteins remain intact. Two
      dimensional averaged images of an exon-trimmed complex closely resemble C complex
      assembled on full-length pre-mRNA, supporting the hypothesis that the electron
      microscopy model of C complex reflects the core structure of a catalytically
      competent particle. Trimming the 3' exon does, however, alter the distribution of
      particles that appear to be missing some density, suggesting that the exon plays
      a role in stabilizing C complex.

PMID- 19761776
TI  - Can cat predation help competitors coexist in seabird communities?
AB  - On oceanic islands, nest site availability can be an important factor regulating
      seabird population dynamics. The potential for birds to secure a nest to
      reproduce can be an important component of their life histories. The dates at
      which different seabird species arrive at colonies to breed will have important
      consequences for their relative chances of success. Early arrival on the island
      allows birds to obtain nests more easily and have higher reproductive success.
      However, the presence of an introduced predator may reverse this situation. For
      instance, in the sub-Antarctic Kerguelen archipelago, early arriving birds suffer
      heavy predation from introduced cats. Cats progressively switch from seabirds to
      rabbits, since the local rabbit population starts to peak after early arriving
      seabird species have already returned to the colony. When late-arriving birds
      arrive, cat predation pressure on seabirds is thus weaker. In this paper, we
      investigate the assumption that the advantage of early nest mnopolization
      conferred to early arriving birds may be counterbalanced by the cost resulting
      from predation. We develop a mathematical model representing a simplified
      situation in which two insular seabird species differ only in their arrival date
      at the colony site and compete for nesting sites. We conclude that predation may
      ensure the coexistence of the two bird species or favor the late-arriving
      species, but only when seasonal variations in predation pressure are large.
      Interestingly, we conclude that arriving early is only favorable until a given
      level where high reproductive success no longer compensates for the long exposure
      to strong predation pressure. Our work suggests that predation can help to
      maintain the balance between species of different phenologies.

PMID- 19761777
TI  - The first peptides: the evolutionary transition between prebiotic amino acids and
      early proteins.
AB  - The issues we attempt to tackle here are what the first peptides did look like
      when they emerged on the primitive earth, and what simple catalytic activities
      they fulfilled. We conjecture that the early functional peptides were short (3-8
      amino acids long), were made of those amino acids, Gly, Ala, Val and Asp, that
      are abundantly produced in many prebiotic synthesis experiments and observed in
      meteorites, and that the neutralization of Asp's negative charge is achieved by
      metal ions. We further assume that some traces of these prebiotic peptides still
      exist, in the form of active sites in present-day proteins. Searching these
      proteins for prebiotic peptide candidates led us to identify three main classes
      of motifs, bound mainly to Mg(2+) ions: D(F/Y)DGD corresponding to the active
      site in RNA polymerases, DGD(G/A)D present in some kinds of mutases, and DAKVGDGD
      in dihydroxyacetone kinase. All three motifs contain a DGD submotif, which is
      suggested to be the common ancestor of all active peptides. Moreover, all three
      manipulate phosphate groups, which was probably a very important biological
      function in the very first stages of life. The statistical significance of our
      results is supported by the frequency of these motifs in today's proteins, which
      is three times higher than expected by chance, with a P-value of 3 x 10(-2). The
      implications of our findings in the context of the appearance of life and the
      possibility of an experimental validation are discussed.

PMID- 19761778
TI  - Independence and interdependence in the nest-site choice by honeybee swarms:
      Agent-based models, analytical approaches and pattern formation.
AB  - In a recent paper List, Elsholtz and Seeley (List et al., 2009) have devised an
      agent-based model of the nest-choice dynamics in swarms of honeybees, and have
      concluded that both interdependence and independence are needed for the bees to
      reach a consensus on the best nest site. We here present a simplified version of
      the model which can be treated analytically with the tools of statistical physics
      and which largely has the same features as the original dynamics. Based on our
      analytical approaches it is possible to characterize the co-ordination outcome
      exactly on the deterministic level, and to a good approximation if stochastic
      effects are taken into account, reducing the need for computer simulations on the
      agent-based level. In the second part of the paper we present a spatial
      extension, and show that transient non-trivial patterns emerge, before consensus
      is reached. Approaches in terms of Langevin equations for continuous field
      variables are discussed.

PMID- 19761779
TI  - The evolutionary path to terminal differentiation and division of labor in
      cyanobacteria.
AB  - A common trait often associated with multicellularity is cellular
      differentiation, which is a spatial separation of tasks through the division of
      labor. In principle, the division of labor does not necessarily have to be
      constrained to a multicellular setting. In this study, we focus on the possible
      evolutionary paths leading to terminal differentiation in cyanobacteria. We
      develop mathematical models for two developmental strategies. First, of
      populations of terminally differentiated single cells surviving by the exchange
      of common goods. Second, of populations exhibiting terminal differentiation in a
      multicellular setting. After testing the two strategies against the effect of
      disruptive mutations (i.e. "cheater" mutants), we assess the effects of selection
      on the optimization of the ratio of vegetative (carbon fixing) to heterocystous
      (nitrogen fixing) cells, which in turn leads to the maximization of the carrying
      capacity for the population density. In addition, we compare the performance of
      differentiated populations to undifferentiated ones that temporally separate
      tasks in accordance to a day/night cycle. We then compare some predictions of our
      model with phylogenetic relationships derived from analyzing 16S rRNA sequences
      of different cyanobacterial strains. In line with studies indicating that group
      or spatial structure are ways to evolve cooperation and protect against the
      spread of cheaters, our work shows that compartmentalization afforded by
      multicellularity is required to maintain the vegetative/heterocyst division in
      cyanobacteria. We find that multicellularity allows for selection to optimize the
      carrying capacity. These results and the phylogenetic analysis indicates that
      terminally differentiated cyanobacteria evolved after undifferentiated species.
      In addition, we show that, in regimes of short daylight periods, terminally
      differentiated species perform worse than undifferentiated species that follow
      the day/night cycle; indicating that undifferentiated species have an
      evolutionary advantage in regimes of short daylight periods.

PMID- 19761780
TI  - CYP450 4A inhibition attenuates O2 induced arteriolar constriction in chronic but
      not acute Goldblatt hypertension.
AB  - We explored the role of 20-hydroxy-5Z, 8Z, 11Z, 14Z-eicosatetraenoic acid (20
      HETE) in oxygen-induced vasoconstriction in a normal renin form of hypertension
      [the 1 kidney-1 clip Goldblatt hypertensive rat (1K1C)] and a high renin form of
      hypertension [the 2 kidney-1 clip Goldblatt hypertensive rat (2K1C)]. A silver
      clip was placed around the left renal artery of adult Sprague-Dawley males. The
      right kidney was removed in the 1K1C group and left intact in the 2K1C group.
      Arteriolar responses to elevation of O(2) concentration in the superfusion
      solution from 0% O(2) to 21% O(2) were determined in the in situ cremaster muscle
      before and after inhibition of cytochrome P450 4A omega-hydroxylase (CYP450 4A)
      with N-methyl-sulfonyl-12, 12-dibromododec-11-enamide (DDMS). Arteriolar
      constriction to elevated PO(2) was enhanced in the chronic 1K1C but not the acute
      1K1C or 2K1C. DDMS eliminated O(2)-induced arteriolar constriction in the 9-week
      1K1C, but had no effect in the 2-week 1K1C, and only partially inhibited O(2)
      induced constriction of arterioles in the 4-week 2K1C rat. These findings
      indicate that although the CYP4A/20-HETE system contributes to arteriolar
      constriction in response to elevated PO(2) in the established stage of 1K1C
      renovascular hypertension, physiological alterations in other mechanisms are the
      primary determinants of O(2)-induced constriction of arterioles in the early and
      developing stages of 1K1C and 2K1C hypertension.

PMID- 19761781
TI  - The neuropharmacology of ADHD drugs in vivo: insights on efficacy and safety.
AB  - Results from in vivo techniques, especially intracerebral microdialysis in freely
      moving rats, have provided insights into potential mechanisms responsible for the
      efficacy and safety of catecholaminergic drugs for ADHD treatment. The drugs
      reviewed come from distinct pharmacological classes: psychostimulant releasing
      agents, eg d-amphetamine; psychostimulant reuptake inhibitors, eg dl-threo
      methylphenidate (dl-MPH), and non-stimulant reuptake inhibitors, eg atomoxetine.
      Psychostimulants, which currently deliver the best efficacy in treating ADHD,
      exhibit the following characteristics on extraneuronal catecholamine
      concentrations in rodent brain in vivo: 1) They enhance the efflux and function
      of both noradrenaline and dopamine in the central nervous system. 2) The increase
      of dopamine efflux that they produce is not limited to cortical regions. 3) They
      have a rapid onset of action with no ceiling on drug effect. d-Amphetamine has a
      mechanism independent of neuronal firing rate, displacing intraneuronal stores of
      catecholamines, delaying their reuptake and inhibiting catabolism by monoamine
      oxidase. dl-MPH has an enigmatic, extraneuronal action that is neuronal firing
      rate-dependent and reuptake transporter-mediated, yet paradoxically, almost as
      powerful as that of d-amphetamine. In safety terms, these powerful
      catecholaminergic effects also make the psychostimulants liable for abuse. Since
      efficacy and safety derive from the same pharmacological mechanisms, it has not
      yet been possible to separate these two components. However, the development of
      once-daily psychostimulant formulations and a prodrug, lisdexamfetamine, has
      improved patient compliance and markedly reduced scope for their diversion/abuse.
      This review will discuss the in vivo pharmacological profiles of approved
      catecholaminergic drugs for treatment of ADHD and implications for their clinical
      efficacy and abuse liability.

PMID- 19761782
TI  - Women process multisensory emotion expressions more efficiently than men.
AB  - Despite claims in the popular press, experiments investigating whether female are
      more efficient than male observers at processing expression of emotions produced
      inconsistent findings. In the present study, participants were asked to
      categorize fear and disgust expressions displayed auditorily, visually, or audio
      visually. Results revealed an advantage of women in all the conditions of
      stimulus presentation. We also observed more nonlinear probabilistic summation in
      the bimodal conditions in female than male observers, indicating greater neural
      integration of different sensory-emotional informations. These findings indicate
      robust differences between genders in the multisensory perception of emotion
      expression.

PMID- 19761783
TI  - Investigating the role of enemies in temporal dynamics: Differential sensitivity,
      competition and stable coexistence.
AB  - The impact of herbivores and other pests on plants varies greatly from year to
      year. Here we develop an analytical model of a temporal niche dynamic as a tool
      to examine how natural fluctuations in pest (enemy) levels may determine
      coexistence in competing annual plant species when one but not the other is
      affected by the pest. We show that the probability and speed with which the
      resistant drives out the sensitive species, coexists with it, or is driven out by
      its sensitive competitor depends on the cost of pest-resistance to the unaffected
      species, the frequency of high pest levels in the habitat and the competitive
      advantage of the sensitive species when the pest is not actively present. The
      interaction is regulated primarily by pest impact on relative seedling survival
      of the two, with relative yield per capita of seeds viable into the following
      season (effective fecundity) the next most vulnerable life-cycle stage.

PMID- 19761784
TI  - Biosynthesis of toxic naturally-occurring seafood contaminants.
AB  - Outbreaks of human illness caused by the consumption of contaminated seafood,
      continues to be a major problem particularly for the shellfish industry. Toxins
      from marine, brackish and freshwater environments, which are often produced as a
      result of harmful algal blooms, have been implicated as the causative agents of
      these poisonings. Commonly, poisoning events have been grouped into one of six
      classes, Paralytic Shellfish Poisoning (PSP), Diarrhetic Shellfish Poisoning
      (DSP), Neurotoxic Shellfish Poisoning (NSP), Ciguatera Fish Poisoning (CFP),
      Azaspiracid Shellfish Poisoning (AZP), and Amnesiac Shellfish Poisoning (ASP).
      The causative agents of these specific poisonings along with their biosyntheses
      are discussed in this review. The highly unusual and complex structures of most
      common seafood toxins have made them interesting targets for biosynthetic
      studies. Many of the toxins presented are biosynthesized via complex pathways
      that have been elucidated either through isotope labelled precursor feeding
      studies and/or characterization of the genes encoding the producing organism's
      biosynthetic machinery. Feeding studies key to our understanding of a particular
      toxin's biosynthesis, such as the incorporation of unusual precursors, as well as
      unique biosynthetic pathways and rare chemical mechanisms involved in the
      assembly process are highlighted. More recently, however, modern genomics-based
      techniques have been used for the elucidation of biosynthetic pathways and these
      are presented in the context of polyketide, non-ribosomal peptide, and hybrid
      pathway derived, toxin assembly.

PMID- 19761785
TI  - Effects of ocular transverse chromatic aberration on near foveal letter
      recognition.
AB  - Transverse chromatic aberration (TCA) smears retinal images of peripheral
      stimuli. In reading, text information is extracted from both foveal and near
      fovea, where TCA magnitude is relatively small and variable. The present study
      investigated whether TCA significantly affects near foveal letter identification.
      Subjects were briefly presented a string of five letters centered one degree of
      visual angle to the left or right of fixation. They indicated whether the middle
      letter was the same as a comparison letter subsequently presented. Letter strings
      were rendered with a reddish fringe on the left edge of each letter and a bluish
      fringe on the right edge, consistent with expected left periphery TCA, or with
      the opposite fringe consistent with expected right periphery TCA. Effect of the
      color fringing on letter recognition was measured by comparing the response
      accuracy for fringed and non-fringed stimuli. Effects of lateral interference
      were examined by manipulating inter-letter spacing and similarity of neighboring
      letters. Results demonstrated significantly improved response accuracy with the
      color fringe opposite to the expected TCA, but decreased accuracy when consistent
      with it. Narrower letter spacing exacerbated the effect of the color fringe,
      whereas letter similarity did not. Our results suggest that TCA significantly
      reduces the ability to recognize letters in the near fovea by impeding
      recognition of individual letters and by enhancing lateral interference between
      letters.

PMID- 19761786
TI  - Motion-induced position shifts occur after motion integration.
AB  - Low-level motion processing in the primate visual system involves two stages. The
      first stage (in V1) contains specialised motion sensors which respond to local
      retinal motion, and the second stage (in MT) pools local signals to encode rigid
      surface motion. Recent psychophysical research shows that motion signals
      influence the perceived position of an object (motion-induced position shift,
      MIPS). In the present paper we investigate the role played by the two processing
      stages in generating MIPS. We compared MIPS induced by single grating components
      (Gabor patches) to MIPS induced by plaids created by combining pairs of
      components. If motion signals at the lowest level of motion analysis (V1)
      influence position assignment, MIPS from plaids should reflect the position shift
      induced by each component when presented separately. On the other hand, if
      signals generated in MT (or later) influence perceived position, then MIPS from
      plaids should be consistent with a motion integration computation on the
      components. Results showed that MIPS from plaids is larger than the MIPS obtained
      from individual components, and can be explained by the output of an integration
      process that combines intersection-of-constraints and vector-sum computations.

PMID- 19761787
TI  - Stimulus uncertainty and perceptual learning: similar principles govern auditory
      and visual learning.
AB  - We examined the impact of variability in speech stimuli on improvement of general
      performance and on accessibility to low-level information as a function of
      practice. Listeners had to discriminate between two similar words in noise in two
      configurations that differed only in their low-level binaural information, which
      was either null or maximal. The difference in performance quantifies the use of
      binaural low-level information. These configurations were presented in three
      training protocols: in separate blocks; in a consistently interleaved manner; and
      in a randomly mixed manner. The first protocol enabled optimal use of the low
      level binaural cues already at the first training session. The second,
      consistently interleaved protocol required more than one training session to
      reach the same performance. The final, mixed protocol did not enable optimal use
      of the low-level cues even after multi-session training. Interestingly, training
      with the first two protocols transferred to the mixed one. These results are in
      line with recent findings in the visual modality. In both modalities, the effects
      of variability on learning can be explained by the introduction of obstructions
      to a search mechanism going down along the sensory processing hierarchy, as
      suggested by the Reverse Hierarchy Theory.

PMID- 19761788
TI  - Correlates of weight loss in persons with metabolic syndrome.
AB  - OBJECTIVE: To identify correlates of weight loss in persons with metabolic
      syndrome. METHODS: Overweight adults (1851) with metabolic syndrome were
      identified among 5643 eligible participants in the U.S. National Health and
      Nutrition Examination Survey, 1999-2004. Survey analysis techniques were used to
      study variation in the frequency of self-reported, intentional weight loss (> or
      =10 lb in the past year) relative to 28 survey variables representing
      characteristics in seven domains: demographic, socioeconomic, lifestyle, health
      status, metabolic risk factor, health advice, and disease diagnosis. RESULTS: An
      estimated 34.8% (SE=0.9) of U.S. adults had metabolic syndrome during the 1999
      2004 period, and among them, 88.4% (0.8) were overweight. The overall frequency
      of weight loss was 14.9% (0.9), but multivariate analysis confirmed significantly
      higher frequencies in persons who had BMI between 35.0 and 39.9 kg/m(2) [24.5%
      (2.8)], who were informed of overweight status by a health professional [19.4%
      (1.6)], who were advised to lose weight for hypertension [23.2% (1.9)], or who
      were diagnosed with diabetes [26.4% (3.2)]. CONCLUSION: In metabolic syndrome,
      the frequency of weight loss may be enhanced when patients understand the reality
      and degree of their overweight status, are advised by a health professional about
      the need to lose weight, and/or appreciate connections between excess weight and
      other co-morbidities.

PMID- 19761789
TI  - Higher coronary heart disease and heart attack morbidity in Appalachian coal
      mining regions.
AB  - BACKGROUND: This study analyzes the U.S. 2006 Behavioral Risk Factor Surveillance
      System survey data (N=235,783) to test whether self-reported cardiovascular
      disease rates are higher in Appalachian coal mining counties compared to other
      counties after control for other risks. METHODS: Dependent variables include self
      reported measures of ever (1) being diagnosed with cardiovascular disease (CVD)
      or with a specific form of CVD including (2) stroke, (3) heart attack, or (4)
      angina or coronary heart disease (CHD). Independent variables included coal
      mining, smoking, BMI, drinking, physician supply, diabetes co-morbidity, age,
      race/ethnicity, education, income, and others. SUDAAN Multilog models were
      estimated, and odds ratios tested for coal mining effects. RESULTS: After control
      for covariates, people in Appalachian coal mining areas reported significantly
      higher risk of CVD (OR=1.22, 95% CI=1.14-1.30), angina or CHD (OR=1.29, 95%
      CI=1.19-1.39) and heart attack (OR=1.19, 95% CI=1.10-1.30). Effects were present
      for both men and women. CONCLUSIONS: Cardiovascular diseases have been linked to
      both air and water contamination in ways consistent with toxicants found in coal
      and coal processing. Future research is indicated to assess air and water quality
      in coal mining communities in Appalachia, with corresponding environmental
      programs and standards established as indicated.

PMID- 19761790
TI  - Mobilization and prevalence of a Fusobacterial plasmid.
AB  - Fusobacterium nucleatum is a Gram-negative anaerobic rod found in dental plaque
      biofilms, and is an opportunistic pathogen implicated in periodontitis as well as
      a wide range of systemic abscesses and infections. Genomic analyses of F.
      nucleatum indicate considerable genetic diversity and a prominent role for
      horizontal gene transfer in the evolution of the species. Several plasmids
      isolated from F. nucleatum, including pFN1, harbor relaxase gene homologs that
      may function in plasmid mobilization. In this investigation we examined the RP4
      mediated mobilization properties of pFN1 and the prevalence of pFN1-related
      sequences in a panel of F. nucleatum clinical isolates. The fusobacterial plasmid
      pFN1 was mobilized by RP4 at a high frequency. Deletion analyses were used to
      delineate the core mobilon of pFN1, which consisted of the relaxase gene (rlx),
      an upstream open reading frame ORF4 and a region of DNA upstream of ORF4 with
      potential nic sites. To examine the prevalence of pFN1 in a panel of clinical
      isolates, total DNA isolated from the strains was hybridized with pFN1
      replication (repA) and rlx gene probes. DNA from strains harboring plasmids known
      to be homologous to pFN1 hybridized with both the repA and rlx probes. Five
      additional strains were rlx-positive but repA-negative, indicating a greater
      prevalence of rlx-related genes in comparison with repA-related genes. Plasmid or
      plasmid-related sequences were identified in 11.5% of the strains examined. These
      findings demonstrate mobilization properties of a fusobacterial plasmid that may
      be important in horizontal gene transfer.

PMID- 19761791
TI  - Changes in anxiety and cognition due to reproductive experience: a review of data
      from rodent and human mothers.
AB  - Rodent research suggests that pregnancy, motherhood and attendant offspring care
      affect changes in neural function and behaviors that are not directly maternal in
      nature, but involve cognition, affect, and responses to stress. Thus, female rats
      having had one pregnancy and bout of rearing (primiparous), or multiple
      pregnancies and bouts of rearing (multiparous), generally show greater resilience
      to stress, decreased anxiety, and better memory abilities than female rats that
      have never experienced motherhood (virgin or nulliparous). Moreover, some studies
      show that these neural changes remain long after the last pregnancy, persisting
      even into old age. In the current review, we will begin by discussing these
      behavioral and neural changes in rodents and provide some information concerning
      their possible mechanisms. Then we will review data from studies examining
      anxiety and cognition in postpartum human mothers. While this data is less
      conclusive than that from non-human animals, it appears that reproductive
      experience may confer some beneficial changes to human mothers in terms of
      lowering the anxiety/stress response and enhancing certain aspects of memory.

PMID- 19761792
TI  - Multiple subcutaneous mycetomas caused by Pseudallescheria boydii: response to
      therapy with oral potassium iodide solution.
AB  - We describe the case of a sixteen-year-old male who presented with multiple
      subcutaneous mycetomas proven on culture to be secondary to Pseudallescheria
      boydi., The lesions responded completely to oral potassium iodide solution. To
      our knowledge this has never been reported in humans.

PMID- 19761793
TI  - Fast, quantitative in situ hybridization of rare mRNAs using 14C-standards and
      phosphorus imaging.
AB  - The use of radiolabelled probes for in situ hybridization (ISH) bears the
      advantage of high sensitivity and quantifiability. The crucial disadvantages are
      laborious hybridization protocols, exposition of hybridized sections to film for
      up to several weeks and the time consuming need to prepare tissue standards with
      relatively short-lived isotopes like (33)P or (35)S for each experiment. The
      quantification of rare mRNAs like those encoding for subunits of neurotransmitter
      receptors is therefore a challenge in ISH. Here, we describe a method for fast,
      quantitative in situ hybridization (qISH) of mRNAs using (33)P-labelled
      oligonucleotides together with (14)C-polymer standards (Microscales, Amersham
      Biosciences) and a phosphorus imaging system (BAS 5000 BioImage Analyzer, Raytest
      Fuji). It enables a complete analysis of rare mRNAs by ISH. The preparation of
      short-lived (33)P-standards for each experiment was replaced by co-exposition and
      calibration of long-lived (14)C-standards together with (33)P-labelled brain
      paste standards. The use of a phosphorus imaging system allowed a reduction of
      exposition time following hybridization from several weeks to a few hours or
      days. We used this approach as an example for applications to quantify the
      expression of GluR1 and GluR2 subunit mRNAs of the alpha-amino-3-hydroxy-5-methyl
      4-isoxazolepropionic acid (AMPA) receptor in the hippocampus of untreated rats,
      and after intraperitoneal application of the organo-arsenic compound dimethyl
      arsenic acid.

PMID- 19761794
TI  - Automatic classification of motor unit potentials in surface EMG recorded from
      thenar muscles paralyzed by spinal cord injury.
AB  - Involuntary electromyographic (EMG) activity has only been analyzed in the
      paralyzed thenar muscles of spinal cord injured (SCI) subjects for several
      minutes. It is unknown if this motor unit activity is ongoing. Longer duration
      EMG recordings can investigate the biological significance of this activity.
      Since no software is currently capable of classifying 24h of EMG data at a single
      motor unit level, the goal of this research was to devise an algorithm that would
      automatically classify motor unit potentials by tracking the firing behavior of
      motor units over 24h. Two channels of thenar muscle surface EMG were recorded
      over 24h from seven SCI subjects with a chronic cervical level injury using a
      custom data logging device with custom software. The automatic motor unit
      classification algorithm developed here employed multiple passes through these 24
      h EMG recordings to segment, cluster, form global templates and classify motor
      unit potentials, including superimposed potentials. The classification algorithm
      was able to track an average of 19 global classes in seven 24-h recordings with a
      mean (+/-SE) accuracy of 89.9% (+/-0.98%) and classify potentials from these
      individual motor units with a mean accuracy of 90.3% (+/-0.97%). The algorithm
      could analyze 24h of data in 2-3 weeks with minimal input from a person, while a
      human operator was estimated to take more than 2 years. This automatic method
      could be applied clinically to investigate the fasciculation potentials often
      found in motoneuron disorders such as amyotrophic lateral sclerosis.

PMID- 19761795
TI  - Chronic infusion of PCP via osmotic mini-pumps: a new rodent model of cognitive
      deficit in schizophrenia characterized by impaired attentional set-shifting
      (ID/ED) performance.
AB  - The identification of animal disease-like models for cognitive symptoms in
      schizophrenia is of central importance to the successful development of
      pharmacological therapies for psychosis resulting in a functional outcome in
      patients. Executive function is one of the most severely affected cognitive
      domains in schizophrenia that remains inadequately treated by existing therapies.
      The rat attentional set-shifting (or intra-dimensional-extra-dimensional (ID/ED))
      task has been developed to test executive function in rodents and successful
      translation of pre-clinical data into the clinical setting now depends on the
      identification of a predictive animal disease-like model. The present study
      investigates whether a continuous 14-day mini-pump infusion of the non
      competitive NMDA receptor antagonist phencyclidine (PCP) leads to a deficit in
      the ID/ED task, and subsequently evaluates the effect of modafinil in this model.
      Lister hooded rats were implanted subcutaneously with osmotic mini-pumps
      containing saline or PCP (15 mg/kg/day) for 14 days followed by a 7-day drug-free
      recovery phase. Rats were then tested in the ID/ED task following an acute
      injection of either vehicle or modafinil. PCP-treated animals displayed a
      selective deficit at the ED shift stage resembling that observed in schizophrenic
      patients. This deficit was reversed by an acute injection of modafinil. The PCP
      induced impairment and its reinstatement by modafinil are quantitatively and
      qualitatively similar to that described earlier by our group following sub
      chronic intraperitoneal PCP administration, indicative that sub-chronic PCP
      infusion via osmotic mini-pumps may represent an attractive alternative to the
      systemic administration protocols generally employed to date.

PMID- 19761796
TI  - Construction and characterization of a stable subgenomic replicon system of a
      Brazilian dengue virus type 3 strain (BR DEN3 290-02).
AB  - Dengue viruses (DENV) cause the most common arboviral disease afflicting men.
      Clinical manifestations range from asymptomatic to dengue hemorrhagic
      fever/dengue shock syndrome (DHF/DSS). The mechanisms involved in the disease
      pathogenesis are not fully understood. The severity of the disease seems to be
      influenced by both viral and host factors. Subgenomic replicons of DENV can be
      used to study viral replication mechanisms and evaluate the effects of antiviral
      drugs on viral replication. The objective was to generate and characterize
      biologically a replicon from a clinical isolate of DENV-3, as part of our studies
      to understand how this new isolate interacts with cells. To obtain this replicon
      several RT-PCR fragments encoding the non-structural proteins genes were cloned
      in high-copy vectors, and used to assemble the replicon in a BAC plasmid vector
      containing a synthetic DNA molecule encoding the 5' and 3' ends of a viral cDNA
      with a T7 DNA-dependent RNA polymerase promoter and a ribozyme. In vitro
      transcribed RNA recovered from this BAC plasmid was transfected into C6/36
      mosquito cells, and dengue virus protein expression was assessed by indirect
      immunofluorescence using polyclonal antibodies. The results showed that the
      replicon was replicated efficiently in cells, demonstrating successful assembly
      of a DENV-3 replicon.

PMID- 19761797
TI  - Rapid quantification of single-nucleotide mutations in mixed influenza A viral
      populations using allele-specific mixture analysis.
AB  - Monitoring antiviral resistance in influenza is critical to public health
      epidemiology and pandemic preparedness activities. Effective monitoring requires
      methods to detect low-level resistance and to monitor the change in resistance as
      a function of time and drug treatment. Resistance-conferring single-nucleotide
      mutations in influenza virus are ideal targets for such methods. In the present
      study, fives sets of paired TaqMan allele-specific PCR (ASPCR) assays were
      developed and validated for quantitative single-nucleotide polymorphism (SNP)
      analysis. This novel method using Delta Ct is termed allele-specific mixture
      analysis (ASMA) or FluASMA. The FluASMA assays target L26F, V27A, A30T, and S31N
      mutations in the A/Albany/1/98 (H3N2) M2 gene and H275Y mutation in the A/New
      Caledonia/20/99 (H1N1) NA gene and have a limit of quantification of 0.25-0.50%
      mutant. The error for % mutant estimation was less than 10% in all FluASMA
      assays, with intra-run Delta Ct coefficient of variance (CoV) at <or=2% and inter
      run Delta Ct CoV at <or=5%. Results from the current study demonstrate that
      FluASMA is a highly sensitive and quantitative SNP analysis method, even for
      minor mutant components (<1%).

PMID- 19761798
TI  - Development of a focus reduction neutralization test (FRNT) for detection of
      mumps virus neutralizing antibodies.
AB  - Although the plaque reduction neutralization test (PRNT) is considered the "gold
      standard" assay for measuring neutralizing antibodies for mumps, it is
      technically demanding, slow and requires large serum volumes, which limits its
      use for investigating mumps vaccine efficacy and population susceptibility.
      Therefore, an immunocolourimetric-based focus reduction neutralization test
      (FRNT) was developed and validated against PRNT using 30 blood donor plasma
      samples (16 positive, 5 equivocal, and 9 negative for mumps IgG by EIA). The
      samples were tested in triplicate by FRNT and PRNT in 10 and 4 separate assay
      runs, respectively, and 50% neutralizing antibody titres calculated using the
      Karber formula. There was good correlation between the two neutralization assays
      (R(2)=0.88). Inter-assay variation for FRNT titres was 2-fold, compared to a 3
      fold variation for PRNT titres. From the distribution of results, a positive cut
      off for FRNT was defined as 1:4. In conclusion, FRNT has similar sensitivity to
      the PRNT and offers the advantage of speed (2 days vs. 7 days), reduced sample
      volume (40 microL vs. 150 microL), and the possibility of automation using 96
      well plates. FRNT appears to be a good substitute for PRNT for characterising the
      immune response to mumps and for vaccine efficacy studies.

PMID- 19761799
TI  - Gender differences in visuospatial planning: an eye movements study.
AB  - Gender studies report a male advantage in several visuospatial abilities. Only
      few studies however, have evaluated differences in visuospatial planning
      behaviour with regard to gender. This study was aimed at exploring whether gender
      may affect the choice of cognitive strategies in a visuospatial planning task
      and, if oculomotor measures could assist in disentangling the cognitive processes
      involved. A computerised task based on the travelling salesperson problem
      paradigm, the Maps test, was used to investigate these issues. Participants were
      required to optimise time and space of a path travelling among a set of sub-goals
      in a spatially constrained environment. Behavioural results suggest that there
      are no gender differences in the initial visual processing of the stimuli, but
      rather during the execution of the plan, with males showing a shorter execution
      time and a higher path length optimisation than females. Males often showed
      changes of heuristics during the execution while females seemed to prefer a
      constant strategy. Moreover, a better performance in behavioural and oculomotor
      measures seemed to suggest that males are more able than females in either the
      optimisation of spatial features or the realisation of the planned scheme.
      Despite inconclusive findings, the results support previous research and provide
      insight into the level of cognitive processing involved in navigation and
      planning tasks, with regard to the influence of gender.

PMID- 19761800
TI  - Effects of physostigmine on the conditioned hyperactivity and locomotor
      sensitization to morphine in rats.
AB  - Repetitive exposure to opioids elicits sensitization to its psychomotor
      stimulating effect and environmental stimuli contribute to this effect. This
      study first developed a procedure that simultaneously measures conditioned
      hyperactivity and locomotor sensitization, and then investigated the effects of
      physostigmine on the development and expression of conditioned hyperactivity and
      locomotor sensitization in rats. Five groups of rats (10-12 rats each) were
      conditioned with a conditioned stimulus (CS) for 20 min and then drug or saline
      paired with CS for 2 h daily for 10 days. Rats were tested 20 min on day 18. On
      day 25, rats were tested 20 min and subsequently 2 h (immediately after morphine
      injection). Although the 20 min locomotion was not different among the rats on
      day 1, rats that received 5 mg/kg morphine during conditioning showed higher
      locomotion than those received saline or 5 mg/kg morphine in the home cage on day
      18 and day 25. Rats received 0.1 mg/kg physostigmine and 5 mg/kg morphine during
      conditioning showed higher locomotion than those received 5 mg/kg morphine on day
      18. On day 25, 0.1 mg/kg physostigmine attenuated the conditioned hyperactivity
      and expression of morphine locomotor sensitization. In contrast, rats received
      0.1 mg/kg physostigmine and 5 mg/kg morphine during conditioning showed higher
      locomotion during 2 h test period than those received 5 mg/kg morphine. In
      conclusion, this study established a procedure that simultaneously study
      conditioned hyperactivity and locomotor sensitization. Physostigmine attenuates
      the expressions but enhances the development of conditioned hyperactivity and
      sensitization and the possible mechanisms are discussed.

PMID- 19761801
TI  - Emotional learning enhances stimulus-specific top-down modulation of sensorimotor
      gating in socially reared rats but not isolation-reared rats.
AB  - Prepulse inhibition (PPI), the suppression of the startle reflex by a preceding
      sensory stimulus (prepulse), can be top-down modulated in both humans and rats.
      This study investigated whether emotional-learning-induced enhancement of PPI in
      rats is prepulse specific. The results show that in socially reared rats, PPI
      elicited by a narrowband-noise prepulse on the broadband-noise background
      (masker) was enhanced after the prepulse became fear conditioned. This fear
      conditioning-modulated PPI was further enhanced by introducing a perceived
      spatial separation between the conditioned prepulse and the broadband-noise
      masker. However, these PPI enhancements disappeared if the conditioned prepulse
      was replaced by a different narrowband-noise prepulse that was not fear
      conditioned. In isolation-reared rats, who had both enhanced baseline startle and
      reduced PPI before conditioning, neither fear conditioning of the prepulse nor
      perceived spatial separation between the conditioned prepulse and noise masker
      could enhance PPI. Thus, the emotional-learning-induced enhancement of PPI in
      socially reared rats is prepulse specific, indicating that auditory processing
      interacts with mnemonic signaling in the formation of top-down modulation of PPI.
      Since the deficiency of attentional modulation of PPI in schizophrenic patients
      is correlated with the symptom severity, the deficiency of top-down modulations
      of PPI in isolation-reared rats is useful for modeling schizophrenia.

PMID- 19761802
TI  - Novel, non-peptidic somatostatin receptor subtype 5 antagonists improve glucose
      tolerance in rodents.
AB  - BACKGROUND: Somatostatin regulates numerous endocrine processes, including
      glucose homeostasis. The contribution and effects of the 5 somatostatin receptors
      are still unclear, in part due to the lack of suitable subtype specific receptor
      antagonists. We explored the effects of two novel, non-peptidic, orally
      bioavailable somatostatin receptor subtype 5 antagonists named Compound A and
      Compound B on glycemia in animal models of type 2 diabetes after an initial in
      vitro characterization. METHODS AND RESULTS: Compound A led to a dose-dependent
      decrease in glucose and insulin excursions during an OGTT in Zucker (fa/fa) rats
      after single treatment by up to 17% and 49%, respectively. Diet-induced obese
      mice showed after three weeks treatment with compounds A and B a dose-dependent
      decrease of the glucose excursion of up to 45% and 37%, respectively. In contrast
      to the acute effect observed in Zucker rats, Compound A showed a dose-dependent
      insulin increase by up to 72%, whereas body weight, liver triglycerides, ALT and
      AST were dose-dependently decreased. CONCLUSIONS: SSTR5 antagonists have the
      potential for short- and long-term improvements of the glucose homeostasis in
      rodent models of type 2 diabetes. Further work on the mechanism and the relevance
      for human disease is warranted.

PMID- 19761803
TI  - Is caseinomacropeptide from milk proteins, an inhibitor of gastric secretion?
AB  - The aim of this work was to study, in vivo, the effect of the ingestion of not
      glycosylated caseinomacropeptide (CMP) on gastric secretion. In Experiments #1
      and #2, 7 calves fitted with a gastric pouch received either a diet without CMP
      (C diet) or C diet in which CMP was introduced (equal to and 5 folds that of CMP
      quantity contained in cow milk, diets CMP1 and CMP5, respectively). In Experiment
      #3, 2 calves (with gastric pouch) were fed C diet followed by an "iv perfusion"
      of CMP. In Experiment #4, 25 calves fed either C, CMP1 or CMP5 diets were fitted
      with a blood catheter for sample collections. The quantities of daily gastric
      secretions seemed few modified by CMP ingestion but the profile of these
      secretions was changed along the day. The most important result is that CMP can
      inhibit gastric secretions (mainly hydrochloric acid) stimulated by the meal, but
      there was no dose-dependent response. No similar observations were obtained after
      perfusion of CMP in jugular vein. CMP was not detected in blood. Results obtained
      in our experiments are not in favor of its significant intestinal absorption.
      Gastrin, somatostatin and VIP could be implicated in the mechanisms of
      regulation.

PMID- 19761804
TI  - Enhancement of pyruvate productivity by inducible expression of a F(0)F(1)-ATPase
      inhibitor INH1 in Torulopsis glabrata CCTCC M202019.
AB  - The aim of this study is to establish a controllable intracellular ATP content
      regulation system applied to the enhancement of pyruvate production in Torulopsis
      glabrata. The INH1 gene, which encodes a F(0)F(1)-ATPase inhibitor from
      Saccharomyces cerevisiae, was expressed under a copper ion inducible promoter in
      the pyruvate producer Torulopsis glabrata CCTCC M202019. The resultant strain was
      designated as T. glabrata INH1. The induction efficiency was measured by the
      inducible expression of an enhanced green fluorescence protein. The copper
      inducible INH1 gene could control the intracellular ATP content (24 h) in an
      extensive range between 0.192 mmol/mg protein and 0.642 mmol/mg protein in a
      flask culture. With T. glabrataINH1, induction with 30 microM of Cu(2+) at 12 h
      in a 3 L fermentor improved pyruvate yield from glucose on biomass by 29% and its
      yield by 20%, respectively.

PMID- 19761805
TI  - Modelling nitrogen assimilation of Escherichia coli at low ammonium
      concentration.
AB  - Modelling is an important methodology in systems biology research. In this paper,
      we presented a kinetic model for the complex ammonium assimilation regulation
      system of Escherichia coli. Based on a previously published model, the new model
      included AmtB mediated ammonium transport and AmtB regulation by GlnK. Protein
      concentrations and several parameter values were determined or refined based on
      new experimental data. Steady state analysis of the model showed that the
      expression of AmtB increased the ammonium assimilation rate 4-5-fold at external
      ammonium concentrations as low as 5muM. Model analysis also suggested that AmtB
      and GS levels were coupled to maximize the assimilation flux and to avoid a
      possible negative ammonia diffusion flux. In addition, model simulation of the
      short term dynamic response to increased external ammonium concentrations implied
      that the maximal rate for GlnB/GlnK uridylylation/deuridylylation might be higher
      for a quick response to environmental changes.

PMID- 19761806
TI  - Elementary research into the transformation BmN cells mediated by the piggyBac
      transposon vector.
AB  - To generate stable transformants of Bombyx mori silkworm BmN cells continuously
      expressing a target gene from a piggyBac-derived vector, BmN cells were
      transfected with a piggyBac vector containing a neomycin-resistance gene, green
      fluorescent protein gene, and human insulin-like growth factor I gene (hIGF-I)
      and a helper plasmid containing the piggyBac transposase sequence under the
      control of the B. mori actin 3 (A3) promoter. With the antibiotic G418, we
      selected stably transformed BmN cells expressing hIGF-I from the piggyBac-derived
      vector containing a neomycin-resistance gene driven by the ie-1 promoter from the
      B. mori nucleopolyhedrovirus. However, no stably transformed BmN cells
      transformed with the piggyBac element vector containing an SV40-promoter-driven
      neomycin-resistance gene were isolated. Determined with an enzyme-linked
      immunosorbent assay, the expression level of hIGF1 was about 7.8ng in 5x10(5)
      cells in which the hIGF-I gene was driven by the sericin-1 promoter, and 147.5ng
      in 5x10(5) cells in which the hIGF-I was under control of B. mori fibroin heavy
      chain gene (fib-H) promoter with its downstream signal peptide sequence. Analysis
      of the chromosomal insertion site by inverse PCR showed that the exogenous DNA
      was inserted into the cell genome randomly or at a TTAA target sequence,
      characteristic of piggyBac element transposition. These results are particularly
      important because piggyBac has been suggested for use in the transgenesis of
      silkworm cells.

PMID- 19761807
TI  - Human growth hormone-transferrin fusion protein for oral delivery in
      hypophysectomized rats.
AB  - Transferrin (Tf)-based recombinant fusion protein approach was investigated to
      achieve oral delivery for human growth hormone (hGH). Plasmid constructs
      expressing the fusion proteins were established by fusing coding sequences of
      both hGH and Tf in frame. Fusion proteins were produced in serum free media by
      transient transfection of human embryonic kidney HEK293 cells. The SDS-PAGE
      analysis of conditioned media showed that fusion proteins expressed at high
      purity with a 100 kDa molecular weight; the Western blot analysis with anti-hGH
      and anti-Tf antibodies verified the identity of fusion proteins. The Nb2 cell
      proliferation and Caco-2 cell Tf receptor (TfR) binding assays demonstrated that
      fusion proteins retained bioactivity of both hGH and Tf, respectively. A helical
      linker was inserted as spacer between hGH- and Tf-domain to enhance the
      bioactivity and the yield of the fusion protein. Two fusion proteins, hGH-Tf (GT)
      and hGH-(H4)(2)-Tf (GHT) were obtained and assessed in hGH-deficient
      hypophysectomized rats for in vivo biological activity. Results from seven-day
      subcutaneous dosing (1.25mg/kg/day) demonstrated that both GT and GHT fusion
      proteins were bioactive in vivo, comparable to native hGH. However, only the GHT,
      but not GT, fusion protein promoted a modest but statistically significant weight
      gain after oral dosing with 12.5mg/kg/day.

PMID- 19761808
TI  - Bioactivity of analogs of the N-terminal region of gastrin-17.
AB  - Gastrin-17-Gly (G17-Gly) has been shown to bind to non-CCK nanomolar and
      micromolar affinity sites on DLD-1 and HT-29 human colonic carcinoma cells and to
      stimulate cellular proliferation. However, in previous studies, we showed that C
      terminal truncation of the gastrin-17 (G17) to the G17 analog G17(1-12) and then
      to G17(1-6)-NH(2) did not remove the ability to bind to DLD-1 cells or to
      activate proliferation. This implies that residues and/or structural motifs
      required for bioactivity at these receptors rest in the N-terminal region of G17.
      In this work, radioligand binding studies conducted with further C-terminally
      truncated analogs revealed that sequences as short as G17(1-4) still bind to a
      single receptor with micromolar affinity. Additionally, cell proliferation assays
      showed that G17(1-12) stimulates proliferation of DLD-1 cells, as of HT-29 cells,
      but the sequences shorter than G17(1-6)-NH(2), including non-amidated G17(1-6),
      were incapable of stimulating proliferation. These observations indicate that the
      tetrapeptide pGlu-Gly-Pro-Trp is the minimum N-terminal sequence for binding to
      the probable growth-promoting site on DLD-1 cells. Since analogs shorter than
      G17(1-6) are able to bind the receptor, these peptides may be of use for
      developing selective antagonists.

PMID- 19761809
TI  - Biphasic protective effect of oxytocin on cardiac ischemia/reperfusion injury in
      anaesthetized rats.
AB  - Oxytocin (OT) is well known for its role in reproduction. However, evidence has
      emerged suggesting a role in cardiovascular system. The aim of this study was to
      investigate the cardioprotective effect of oxytocin on ischemia/reperfusion (I/R)
      injury in an in vivo rat. Myocardial ischemia, was surgically induced by means of
      left anterior descending coronary artery occlusion for 25 min followed by
      reperfusion for 120 min. Infarct size was evaluated using the staining agent
      2,3,5-triphenyltetrazolium chloride. Creatine kinase-MB isoenzyme (CK-MB) and
      lactate dehydrogenase (LDH) levels in plasma were analyzed to assess the degree
      of cardiac injury. Intraperitoneal administration of OT 0.001, 0.01 and 0.1
      microg significantly reduced infarct size, LDH and CK-MB levels as compared to
      control (I/R) group and it had a biphasic effect on the reduction of
      ischemia/reperfusion injury. This biphasic effect was revealed as a U-shaped
      curve in which efficacy was optimal between very low and very high doses.
      Furthermore there were no significant differences in mean arterial pressure or
      heart rate between the OT treatment groups and control group during I/R. Blockade
      of specific OT receptors by atosiban (10(-6)M) abolished or attenuated the effect
      of OT preconditioning. The result of this study shows that OT possess a dose
      dependent cardioprotective effect against ischemia/reperfusion injury and so
      study of OT preconditioning may provide a new target site for therapeutic
      exploitation.

PMID- 19761810
TI  - Reactivation of tabun-hAChE investigated by structurally analogous oximes and
      mutagenesis.
AB  - The nerve agent tabun inhibits the essential enzyme acetylcholinesterase (AChE)
      by a rapid phosphoramidation of the catalytic serine residue. Oximes, such as
      K027 and HLo-7, can reactivate tabun-inhibited human AChE (tabun-hAChE) whereas
      the activity of their close structural analogue HI-6 is notably low. To
      investigate HI-6, K027 and HLo-7, residues lining the active-site gorge of hAChE
      were substituted and the effects on kinetic parameters for reactivation were
      determined. None of the mutants (Asp74Asn, Asp74Glu, Tyr124Phe, Tyr337Ala,
      Tyr337Phe, Phe338Val and Tyr341Ala) were able to facilitate HI-6-mediated
      reactivation of tabun-hAChE. In contrast, Tyr124Phe and Tyr337Phe induce a 2-2.5
      fold enhancement of the bimolecular rate constant for K027 and HLo-7. The largest
      effects on the dissociation constant (3.5-fold increase) and rate constant (20
      fold decrease) were observed for Tyr341Ala and Asp74Asn, respectively. These
      findings demonstrate the importance of residues located distant from the
      conjugate during the reactivation of tabun-hAChE.

PMID- 19761811
TI  - Identification of genomic biomarkers for concurrent diagnosis of drug-induced
      renal tubular injury using a large-scale toxicogenomics database.
AB  - Drug-induced renal tubular injury is one of the major concerns in preclinical
      safety evaluations. Toxicogenomics is becoming a generally accepted approach for
      identifying chemicals with potential safety problems. In the present study, we
      analyzed 33 nephrotoxicants and 8 non-nephrotoxic hepatotoxicants to elucidate
      time- and dose-dependent global gene expression changes associated with proximal
      tubular toxicity. The compounds were administered orally or intravenously once
      daily to male Sprague-Dawley rats. The animals were exposed to four different
      doses of the compounds, and kidney tissues were collected on days 4, 8, 15, and
      29. Gene expression profiles were generated from kidney RNA by using Affymetrix
      GeneChips and analyzed in conjunction with the histopathological changes. We used
      the filter-type gene selection algorithm based on t-statistics conjugated with
      the SVM classifier, and achieved a sensitivity of 90% with a selectivity of 90%.
      Then, 92 genes were extracted as the genomic biomarker candidates that were used
      to construct the classifier. The gene list contains well-known biomarkers, such
      as Kidney injury molecule 1, Ceruloplasmin, Clusterin, Tissue inhibitor of
      metallopeptidase 1, and also novel biomarker candidates. Most of the genes
      involved in tissue remodeling, the immune/inflammatory response, cell
      adhesion/proliferation/migration, and metabolism were predominantly up-regulated.
      Down-regulated genes participated in cell adhesion/proliferation/migration,
      membrane transport, and signal transduction. Our classifier has better prediction
      accuracy than any of the well-known biomarkers. Therefore, the toxicogenomics
      approach would be useful for concurrent diagnosis of renal tubular injury.

PMID- 19761812
TI  - Levels of salivary IgA antibodies to Candida spp. in HIV-infected adult patients:
      a systematic review.
AB  - OBJECTIVE: To perform a systematic review of published data with the aim of
      evaluating the levels of IgA antibodies to Candida albicans in HIV-infected adult
      patients. METHODS: The search strategy was based on PubMed, Web of Science,
      Google Scholar, Cochrane and EMBASE databases. Also, the reference lists of
      included studies were searched. All abstracts found by electronic searches were
      independently scrutinized by two reviewers. To be eligible for review, the
      controlled studies had to present the following characteristics: samples of both
      HIV-infected adults and noninfected adults; appropriate HIV-diagnostic tests for
      both patient groups (case and control); IgA-diagnostic test applied to a similar
      population sample. RESULTS: Of 144 studies found, only six met the initial
      eligibility criteria, but three were excluded after a thorough analysis. To
      assess the methodological quality of the three remaining studies, they were
      categorized according the risk of bias. The three selected studies revealed that
      the levels of C. albicans-specific IgA antibody were higher in HIV-infected
      individuals compared with the control group. CONCLUSION: Adequate IgA antibody
      responses to C. albicans appear to be maintained, since the levels of these
      antibodies were higher in all studies selected. Although the findings of this
      systematic review are encouraging, the scientific evidence should be interpreted
      carefully because there are only a few reports in the literature, mostly because
      of the lack of important methodological details or the varying methodologies
      employed.

PMID- 19761813
TI  - Functional asymmetry in the descending cardiovascular pathways from dorsomedial
      hypothalamic nucleus.
AB  - Neurons in the dorsomedial hypothalamus (DMH) play a key role in mediating
      tachycardia elicited by emotional stress. DMH activation by microinjections of
      the GABA(A) antagonist evokes tachycardia and physiological changes typically
      seen in experimental stress. DMH inhibition abolishes the tachycardia evoked by
      stress. Based on anatomic evidences for lateralization in the pathways from DMH,
      we investigated a possible inter-hemispheric difference in DMH-evoked
      cardiovascular responses. In anesthetized rats we compared changes in heart rate
      (HR), renal sympathetic activity (RSNA), mesenteric blood flow (MBF) and tail
      vascular conductance produced by activation of right (R) and left (L) sides of
      the DMH. We also evaluated the tachycardia produced by air jet stress after
      inhibition of R or L DMH. There were always greater increases in RSNA when
      bicuculline was injected ipsilaterally to the side where these parameters were
      recorded (average DeltaRSNA: L=+50% and R=+26%; P<0.05). Compared to pre
      injection values, right DMH activation caused pronounced decrease (0.87+/-0.1%
      vs. 0.4+/-0.11%/mm Hg; P<0.05), whereas bicuculline methiodide (BMI) into left
      DMH produced no significant changes (0.95+/-0.09% vs. 1.04+/-0.25%/mm Hg) in tail
      vascular conductance. R or L DMH disinhibition produced decreases in MBF, but no
      differences in the range of these changes were observed. Activation of the right
      DMH caused greater tachycardia compared to the left DMH activation (average
      DeltaHR: R=+92 bpm; L=+48 bpm; P<0.05). Tachycardia evoked by air jet stress was
      smallest after right DMH inhibition (average DeltaHR: R=+57 bpm and L=+134 bpm;
      P<0.05). These results indicate that the descending cardiovascular pathways from
      DMH are predominantly lateralized and the right DMH might exert a prominent
      control on heart rate changes during emotional stress.

PMID- 19761814
TI  - Mutant torsinA interacts with tyrosine hydroxylase in cultured cells.
AB  - A specific mutation (DeltaE302/303) in the torsinA gene underlies most cases of
      dominantly inherited early-onset torsion dystonia. This mutation causes the
      protein to aggregate and form intracellular inclusion bodies in cultured cells
      and animal models. Co-expression of the wildtype and mutant proteins resulted in
      the redistribution of the wildtype protein from the endoplasmic reticulum to
      inclusion bodies in cultured HEK293 cells, and this was associated with increased
      interaction between the two proteins. Expression of DeltaE302/303 but not
      wildtype torsinA in primary postnatal midbrain neurons resulted in the formation
      of intracellular inclusion bodies, predominantly in dopaminergic neurons.
      Tyrosine hydroxylase was sequestered in these inclusions and this process was
      mediated by increased protein-protein interaction between mutant torsinA and
      tyrosine hydroxylase. Analysis in an inducible neuroblastoma cell culture model
      demonstrated altered tyrosine hydroxylase activity in the presence of the mutant
      but not wildtype torsinA protein. Our results suggest that the interaction of
      tyrosine hydroxylase and mutant torsinA may contribute to the phenotype and
      reported dopaminergic dysfunction in torsinA-mediated dystonia.

PMID- 19761815
TI  - Water transport between CNS compartments: contributions of aquaporins and
      cotransporters.
AB  - Large water fluxes continuously take place between the different compartments of
      the brain as well as between the brain parenchyma and the blood or cerebrospinal
      fluid. This water flux is tightly regulated but may be disturbed under
      pathological conditions that lead to brain edema formation or hydrocephalus. The
      molecular pathways by which water molecules cross the cell membranes of the brain
      are not well-understood, although the discovery of aquaporin 4 (AQP4) in the
      brain improved our understanding of some of these transport processes,
      particularly under pathological conditions. In the present review we introduce
      another family of transport proteins as water transporters, namely the
      cotransporters and the glucose uniport GLUT1. In direct contrast to the
      aquaporins, these proteins have an inherent ability to transport water against an
      osmotic gradient. Some of them may also function as water pores in analogy to the
      aquaporins. The putative role of cotransport proteins and uniports for the water
      flux into the glial cells, through the choroid plexus and across the endothelial
      cells of the blood-brain-barrier will be discussed and compared to the
      contribution of the aquaporins.

PMID- 19761816
TI  - Water permeability through aquaporin-4 is regulated by protein kinase C and
      becomes rate-limiting for glioma invasion.
AB  - Glial-derived tumors, gliomas, are highly invasive cancers that invade normal
      brain through the extracellular space. To navigate the tortuous extracellular
      spaces, cells undergo dynamic changes in cell volume, which entails water flux
      across the membrane through aquaporins (AQPs). Two members of this family, AQP1
      and AQP4 are highly expressed in primary brain tumor biopsies and both have a
      consensus phosphorylation site for protein kinase C (PKC), which is a known
      regulator of glioma cell invasion. AQP4 colocalizes with PKC to the leading edge
      of invading processes and clustered with chloride channel (ClC2) and K(+)-Cl(-)
      cotransporter 1 (KCC1), believed to provide the pathways for Cl(-) and K(+)
      secretion to accomplish volume changes. Using D54MG glioma cells stably
      transfected with either AQP1 or AQP4, we show that PKC activity regulates water
      permeability through phosphorylation of AQP4. Activation of PKC with either
      phorbol 12-myristate 13-acetate or thrombin enhanced AQP4 phosphorylation,
      reduced water permeability and significantly decreased cell invasion. Conversely,
      inhibition of PKC activity with chelerythrine reduced AQP4 phosphorylation,
      enhanced water permeability and significantly enhanced tumor invasion. PKC
      regulation of AQP4 was lost after mutational inactivation of the consensus PKC
      phosphorylation site S180A. Interestingly, AQP1 expressing glioma cells, by
      contrast, were completely unaffected by changes in PKC activity. To demonstrate a
      role for AQPs in glioma invasion in vivo, cells selectively expressing AQP1, AQP4
      or the mutated S180A-AQP4 were implanted intracranially into SCID mice. AQP4
      expressing glioma cells showed significantly reduced invasion compared to AQP1
      and S180 expressing tumors as determined by quantitative stereology, consistent
      with a differential role for AQP1 and AQP4 in this process.

PMID- 19761817
TI  - Early modifications in N-methyl-D-aspartate receptor subunit mRNA levels in an
      oxygen and glucose deprivation model using rat hippocampal brain slices.
AB  - Glutamatergic N-methyl-d-aspartate NMDA receptors (NMDAR) are considered to play
      a key role in ischemia-induced damage. Long-term (hours) changes in their
      expression upon ischemia have been shown. Here we report short-term changes in
      the mRNA levels of the major hippocampal NMDAR subunits (NR1, NR2A and NR2B), as
      well as c-fos, in an ex vivo ischemia model using hippocampal slices. This effect
      can be observed also in a calcium free incubation solution. Striking early
      decreases in the NMDAR subunit mRNA levels were observed after 30 min of oxygen
      and glucose deprivation (OGD) as well as a partial recovery when the tissues were
      returned to the balanced salt solution (reperfusion-like period) for 3 h. Since
      OGD-induced damage has been reported to be a consequence of the increase in OGD
      related glutamate release, we also analyzed NMDAR mRNA levels following increased
      glutamate levels in hippocampal sections in which no significant effects on NMDAR
      subunit mRNA levels were detected. Furthermore, we describe that the presence of
      MK-801 (a selective NMDAR antagonist), CNQX (a selective AMPA/kainate receptor
      antagonist) or their combined action in the incubation solution is able to induce
      a significant decrease in NMDAR expression but in these conditions the OGD does
      not induce further decreases in mRNA levels. We suggest that the mechanisms
      triggered during OGD to downregulate mRNA levels of NMDAR subunits could be the
      same than those induced by glutamate receptor antagonists.

PMID- 19761818
TI  - Estrous cycle phase and gonadal hormones influence conditioned fear extinction.
AB  - Gonadal hormones modulate fear acquisition, but less is known about the influence
      of gonadal hormones on fear extinction. We assessed sex differences and the
      influence of gonadal hormone fluctuations and exogenous manipulations of estrogen
      and progesterone on acquisition, extinction learning and extinction recall in a 3
      day auditory fear conditioning and extinction protocol. Experiments were
      conducted on males and naturally cycling female rats. Regarding female rats,
      significant differences in fear extinction were observed between subgroups of
      females, depending on their phase of the estrous cycle. Extinction that took
      place during the proestrus (high estrogen/progesterone) phase was more fully
      consolidated, as evidenced by low freezing during a recall test. This suggests
      that estrogen and/or progesterone facilitate extinction. In support of this,
      injection of both estrogen and progesterone prior to extinction learning in
      female rats during the metestrus phase of the cycle (low estrogen/progesterone)
      facilitated extinction consolidation, and blockade of estrogen and progesterone
      receptors during the proestrus phase impaired extinction consolidation. When
      comparing male to female rats without consideration of the estrous cycle phase,
      no significant sex differences were observed. When accounting for cycle phase in
      females, sex differences were observed only during extinction recall. Female rats
      that underwent extinction during the metestrus phase showed significantly higher
      freezing during the recall test relative to males. Collectively, these data
      suggest that gonadal hormones influence extinction behavior possibly by
      influencing the function of brain regions involved in the consolidation of fear
      extinction. Moreover, the elevated fear observed in female relative to male rats
      during extinction recall suggests that gonadal hormones may in part play a role
      in the higher prevalence of anxiety disorders in women.

PMID- 19761819
TI  - Probenecid treatment enhances retinal and brain delivery of N-4
      benzoylaminophenylsulfonylglycine: an anionic aldose reductase inhibitor.
AB  - Anion efflux transporters are expected to minimize target tissue delivery of N-[4
      (benzoylaminophenyl)sulfonyl]glycine (BAPSG), a novel carboxylic acid aldose
      reductase inhibitor, which exists as a monocarboxylate anion at physiological
      conditions. Therefore, the objective of this study was to determine whether BAPSG
      delivery to various eye tissues including the retina and the brain can be
      enhanced by probenecid, a competitive inhibitor of anion transporters. To
      determine the influence of probenecid on eye and brain distribution of BAPSG,
      probenecid was administered intraperitoneally (120 mg/kg body weight; i.p.) 20
      min prior to BAPSG (50 mg/kg; i.p.) administration. Drug disposition in various
      eye tissues including the retina and the brain was determined at 15 min, 1, 2 and
      4h after BAPSG dose in male Sprauge-Dawley rats. To determine whether probenecid
      alters plasma clearance of BAPSG, influence of probenecid (120 mg/kg; i.p.) on
      the plasma pharmacokinetics of intravenously administered BAPSG (15 mg/kg) was
      studied as well. Finally, the effect of probenecid co-administration on the
      ocular tissue distribution of BAPSG was assessed in rabbits following topical
      (eye drop) administration. Following pretreatment with probenecid in the rat
      study, retinal delivery at 1h was increased by about 11-fold (2580 ng/g vs. 244
      ng/g; p<0.05). Further, following probenecid pretreatment, significant BAPSG
      levels were detectable in the brain (45 + or - 20 ng/g) at 1h, unlike controls
      where the drug was not detectable. Plasma concentrations, plasma elimination half
      life, and total body clearance of intravenously administered BAPSG were not
      altered by i.p. probenecid pretreatment. In the topical dosing study, a
      significant decline in BAPSG delivery was observed in the iris-ciliary body but
      no significant changes were observed in other tissues of the anterior segment of
      the eye including tears. Thus, inhibition of anion transporters is a useful
      approach to elevate retinal and brain delivery of BAPSG.

PMID- 19761820
TI  - A HPTLC densitometric method for the determination of aloeverose in Aloe vera
      gel.
AB  - Aloe vera gel is a familiar ingredient in a range of widely available and
      advertisement healthcare and cosmetic products. As to date there are no
      documented reports on the standardization of A. vera gel and the following study
      is an attempt in this direction. A. vera gel was evaluated for its aloeverose
      content for the first time. Aloeverose, was separated on a thin-layer of silica
      gel by isocratic gradient elution technique was determined by using HPTLC
      photodensitometry. The proposed method is simple and sensitive and can be used
      for the routine assay of aloeverose in phytomedicines containing A. vera gel.

PMID- 19761821
TI  - Fluorescence spectroscopy of small peptides interacting with microheterogeneous
      micelles.
AB  - Many peptides containing tryptophan have therapeutic uses and can be studied by
      their fluorescent properties. The biological activity of these peptides involves
      interactions with many cellular components and micelles can function as carriers
      inside organisms. We report results from the interaction of small peptides
      containing tryptophan with several microheterogeneous systems: sodium dodecyl
      sulphate (SDS) micelles; sodium dodecyl sulphate-poly(ethylene oxide) (SDS-PEO)
      aggregates; and neutral polymeric micelles. We observed that specific parameters,
      such as wavelength of maximum emission and fluorescence anisotropy, could be used
      to ascertain the occurrence of interactions. Affinity constants were determined
      from changes in the intensity of emission while structural modifications in
      rotameric conformations were verified from time-resolved measurements.
      Information about the location and diffusion of peptides in the
      microheterogeneous systems were obtained from tryptophan emission quenching
      experiments using N-alkylpyridinium ions. The results show the importance of
      electrostatic and hydrophobic effects, and of the ionization state of charged
      residues, in the presence of anionic and amphiphilic SDS in the
      microheterogeneous systems. Conformational stability of peptides is best
      preserved in the interaction with the neutral polymeric micelles.

PMID- 19761822
TI  - Influence of dendrimer generation and polyethylene glycol length on the
      biodistribution of PEGylated dendrimers.
AB  - Dendrimers are a potential drug carrier. Because modification with polyethylene
      glycol (PEG) is known to improve the blood retention, PEGylated dendrimers have
      been studied as a useful drug carrier. In this study, three types of PEGylated L
      lysine-bearing polyamidoamine dendrimers (PEG2k-Lys-PAMAM (G4), PEG5k-Lys-PAMAM
      (G4), PEG2k-Lys-PAMAM (G5)) were synthesized, which are composed of a dendrimer
      of different generations (generations 4 and 5) and PEG chains with different
      molecular weights (2k and 5k). An acetylated L-lysine-bearing dendrimer was also
      synthesized as a non-PEGylated dendrimer. Bifunctional
      diethylenetriaminepentaacetic acid (pSCN-benzyl-DTPA) was bound to the epsilon 
      amino group of lysine in a dendrimer, to be labeled with radioactive indium-111.
      These PEGylayed dendrimers showed longer blood retention and lower accumulation
      in other normal organs such as the kidneys than the non-PEGylated dendrimer. The
      PEGylated dendrimers with the higher generation and the longer PEG led the
      greater blood retention.

PMID- 19761823
TI  - PTEN attenuates PIP3/Akt signaling in the cochlea of the aging CBA/J mouse.
AB  - We have previously reported the activation of cell death pathways in the sensory
      cells of the aging cochlea. Here we investigate age-associated changes in
      survival mechanisms focusing on phosphatidylinositol 3,4,5-trisphosphate
      (PIP(3))/Akt signaling. The animal model is the CBA/J mouse of 18 months of age
      prior to the onset of major functional loss (ABR thresholds, 26+/-8 dB SPL) which
      is compared to young animals of 3 months of age (ABR thresholds, 19+/-7 dB SPL).
      Immunostaining on cochlear cryosections revealed a wide-spread distribution of
      PIP(3) in the cochlea which was markedly attenuated in old animals in inner and
      outer hair cells, Deiters cells and pillar cells. Protein levels of the lipid
      phosphatase PTEN which regulates PIP(3) increased in those cells with aging while
      its mRNA did not, suggesting an age-related reduction of PTEN degradation.
      Furthermore, staining intensity of phosphorylated PTEN (ser380) and its nuclear
      localization increased. Consistent with a reduction of PIP(3), the
      phosphorylation of the downstream target Akt at threonine 308 significantly
      decreased in outer hair cells. The results suggest a decline of the survival
      capacity of aging outer hair cells due to a decrease in PIP(3)/Akt signaling
      caused by an increase of PTEN.

PMID- 19761824
TI  - The hepatoprotective and antifibrotic effects of Saururus chinensis against
      carbon tetrachloride induced hepatic fibrosis in rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Saururus chinensis (Lour.) Baill (Saururaceae)
      has been used in Chinese folk medicine for treatment of various diseases, such as
      edema, jaundice, gonorrhea, antipyretic, diuretic, and antiinflammatory agents.
      AIM OF THE STUDY: Our aim was to evaluate the hepatoprotective and antifibrotic
      effects of Saururus chinensis extract (SC-E) in carbon tetrachloride (CCl(4))
      induced liver fibrosis rats. MATERIALS AND METHODS: The SC-E (70 mg/kg) was
      administrated via gavage once a day starting from the onset of CCl(4) treatment
      (14 weeks) for subsequent 8 weeks. Evaluated with liver index, serum levels of
      alanine aminotransferase (ALT), aspartate aminotransferase (AST), hyaluronic acid
      (HA), hepatic malondialdehyde (MDA) content, and superoxide dismutase (SOD)
      activity, total cholesterol (TC), triglyceride (TG), total lipoprotein (TP),
      albumin (ALB), hydroxyproline (HYP), total antioxidant capacity (T-AOC), laminin
      (LN), type III collagen terminal peptide (PC-IIINP), and type IV collagen (IV-C),
      as well as with histopathologic changes of liver. RESULTS: SC-E effectively
      reduced the elevated levels of liver index, serum ALT, AST, HA, and hepatic MDA
      contents, enhance the reduced hepatic SOD activity in CCl(4)-treated rats. The
      histopathological analysis suggested that SC-E obviously alleviated the degree of
      liver fibrosis induced by CCl(4). CONCLUSIONS: Those results suggest SC-E has
      protective and therapeutic effects on liver fibrosis induced by CCl(4).

PMID- 19761825
TI  - Antiviral activity-guided fractionation from Araucaria angustifolia leaves
      extract.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Araucaria angustifolia (Bert.) O. Kuntze
      (Araucariaceae) is a Brazilian medicinal plant traditionally used for the
      treatment of various illnesses including dried skin, wounds, shingles, and
      sexually transmitted diseases. AIM OF THE STUDY: The rationale of the study was
      to provide evidence of its antiherpes activity in order to confirm its popular
      use that could be related to herpes disease. MATERIALS AND METHODS: The crude
      hydroethanolic extract (HE) obtained from Araucaria angustifolia leaves was
      submitted to a sequential liquid-liquid extraction with solvents of increased
      polarity. The HE and fractions obtained were evaluated for cytotoxicity and
      antiherpes activity (Herpes Simplex Virus type 1) by MTT assay. The most active
      fractions were selected to perform an in vitro antiviral activity-guided
      chromatographic fractionation. RESULTS: The ethyl acetate (EA) and n-butanol (NB)
      fractions have shown the best results for antiherpetic activity and their further
      fractionation yielded 22 subfractions. From these subfractions, 14 were active,
      and the most potent antiherpetic activity was obtained for NB1-4 subfraction with
      selectivity index (SI) of 57.51. Chemical analysis of NB1-4 subfractions revealed
      the presence of proanthocyanidins and the known biflavonoids (bilobetin, II-7-O
      methyl-robustaflavone and cupressuflavone). The same biflavonoids have been
      detected in EA subfractions. CONCLUSION: The present study has shown that the
      hydroethanolic extract from Araucaria angustifolia leaves as well as many
      different fractions and subfractions exhibited antiherpes activity, supporting
      the use of this plant species in folk medicine.

PMID- 19761826
TI  - Chelidonium majus is not hepatotoxic in Wistar rats, in a 4 weeks feeding
      experiment.
AB  - AIM OF THE STUDY: Aerial parts of Chelidonium majus L. (Papaveraceae family) are
      traditionally used in the treatment of gallstones and dyspepsia, however several
      cases of hepatotoxicity are reported. In this work we evaluated the effects on
      liver function of a C. majus extract, obtained from the herbal material
      responsible for one case of hepatotoxicity. MATERIALS AND METHODS: Experiments
      were performed in Wistar rats, after oral administration of doses corresponding
      to 1.5 and 3g/(kg day) of herbal drug, for 2 or 4 weeks. Blood samples were
      collected to perform biochemical analysis, whereas liver samples were used for
      histomorphological and immunohistochemical examination along with the
      determination of oxidative stress parameters. RESULTS: No significant
      modification in animal body weight, food consumption, enzyme activities, hepatic
      histomorphology and MDA formation, at either time or dosage level. Conversely, C.
      majus induced a slight but significant decrease of GSH levels and SOD activity,
      especially at the high dose. CONCLUSIONS: Our study suggests that C. majus, at
      doses about 50 and 100 times higher than those generally used in humans, does not
      alter hepatic function. However, the reduction in GSH levels and SOD activity
      suggests particular attention in use of C. majus or its preparations in
      situations (pharmacological treatments, physio-pathological conditions, etc.)
      that can compromise liver function.

PMID- 19761827
TI  - Traditional antimalarial phytotherapy remedies in herbal markets in southern
      Ghana.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Although traditional antimalarial plant remedies
      in herbal markets are a very important component of the health care system in
      Ghana this has not been previously studied to allow for the formulation of
      effective strategy for malaria control in Ghana. AIM OF STUDY: The main objective
      of the present study was to collect and analyse data on the antimalarial plant
      remedies in herbal markets in southern Ghana. MATERIALS AND METHODS: Herborists
      were interviewed using a validated questionnaire and species of plants were
      identified using a combination of field photo guides, local names and voucher
      specimens. RESULTS: A total of 71 herborists (95.8% female) were interviewed.
      There were potential correlations between different parameters and variables such
      as ethnic groups, type of vendor and age-groups. The study revealed 29 species of
      plants belonging to 22 families being sold for the treatment of malaria. The
      detailed use of these plants is documented. The most frequently mentioned species
      of plants were Morinda lucida Benth., Indigofera sp. and Nauclea latifolia Sm.
      The majority (82.8%) of the plant materials were sold in the dried state and 6.9%
      were sold in fresh state. About 76.2% of the herbal remedies were sold throughout
      the year while 23.8% were scarce in the dry season. The cost of treatment of
      malaria using the herbal remedies ranged from 1 to 2 United States Dollars (USD).
      CONCLUSION: Standardization of names and authentication of plant materials using
      organoleptic, phytochemical and DNA barcoding techniques as well as further
      research on efficacy, safety and dosage prescriptions for both fresh and dried
      plant materials being sold for the treatment of malaria in southern Ghana are
      needed.

PMID- 19761828
TI  - Differential efficiency of induction of various lambdoid prophages responsible
      for production of Shiga toxins in response to different induction agents.
AB  - Shiga toxin-producing Escherichia coli (STEC) is a group of pathogenic strains
      responsible for bloody diarrhea and hemorrhagic colitis, with often severe
      complications. Shiga toxins are the main factors causing the phathogenicity of
      STEC. Production of these toxins depends on the presence of stx1 and stx2 genes,
      which are located on lambdoid prophages, and their expression is stimulated upon
      prophage induction. Therefore, a transition of the phage genome from the prophage
      state to an extrachromosomal genetic element, and its further propagation, is
      crucial for the pathogenic effects. However, our knowledge on specific conditions
      for induction of these prophages in bacteria occurring in human intestine is very
      limited. In this report we present results of our studies on five different
      phages, originally occurring in STEC strains, in comparison to bacteriophage
      lambda. We found that efficiencies of induction of prophages and their further
      development vary considerably in response to different induction agents.
      Moreover, efficiency of progeny phage production might be modulated by other
      factors, like temperature or bacterial growth rate. Therefore, it is likely that
      pathogenicity of different STEC strains may be significantly different under
      specific conditions in their natural habitats.

PMID- 19761829
TI  - Sperm DNA damage and its relation with leukocyte DNA damage.
AB  - DNA fragmentation in human sperm has been related to endogenous and exogenous
      factors. Exogenous factors can also affect leukocyte DNA integrity. This study
      evaluated the relation between sperm DNA damage and leukocyte DNA integrity, as a
      predictor of exogenous factors. DNA damage in the sperm and leukocytes of 41
      individuals undergoing ICSI were measured by Comet assay. In addition, sperm
      chromatin dispersion (SCD) was carried out on semen samples. A positive
      correlation was observed between the DNA integrity of sperm with leukocytes. When
      patients were divided into low and high DNA exposure groups, sperm DNA
      fragmentation was significantly different between the two groups. Cleavage rate
      and embryo quality showed significant correlation with leukocyte DNA integrity.
      The results showed that leukocyte DNA integrity could be used to identify
      individuals at high risk in order to reduce the extent of DNA damage in patients
      before ICSI in order to improve the subsequent outcome of this procedure.

PMID- 19761830
TI  - Sulfur mustard analog induces oxidative stress and activates signaling cascades
      in the skin of SKH-1 hairless mice.
AB  - A monofunctional analog of the chemical warfare agent sulfur mustard (HD), 2
      chloroethyl ethyl sulfide (CEES), induces tissue damage similar to HD. Herein we
      studied the molecular mechanisms associated with CEES-induced skin inflammation
      and toxicity in SKH-1 hairless mice. Topical CEES exposure caused an increase in
      oxidative stress as observed by enhanced 4-hydroxynonenal and 5,5-dimethyl-2-(8
      octanoic acid)-1-pyrroline N-oxide protein adduct formation and an increase in
      protein oxidation. The CEES-induced increase in the formation of 8-oxo-2
      deoxyguanosine indicated DNA oxidation. CEES exposure instigated an increase in
      the phosphorylation of mitogen-activated protein kinases (MAPKs; ERK1/2, JNK, and
      p38). After CEES exposure, a significant increase in the phosphorylation of Akt
      at Ser473 and Thr308 was observed as well as upregulation of its upstream
      effector, PDK1, in mouse skin tissue. Subsequently, CEES exposure caused
      activation of AP-1 family proteins and the NF-kappaB pathway, including
      phosphorylation and degradation of IkappaBalpha in addition to phosphorylation of
      the NF-kappaB essential modulator. Collectively, our results indicate that CEES
      induces oxidative stress and the activation of the transcription factors AP-1 and
      NF-kappaB via upstream signaling pathways including MAPKs and Akt in SKH-1
      hairless mouse skin. These novel molecular targets could be supportive in the
      development of prophylactic and therapeutic interventions against HD-related skin
      injury.

PMID- 19761831
TI  - Reduced activity of glutamine synthetase in Rhodospirillum rubrum mutants lacking
      the adenylyltransferase GlnE.
AB  - In the nitrogen-fixing bacterium Rhodospirillum rubrum, the GlnE
      adenylyltransferase (encoded by glnE) catalyzes reversible adenylylation of
      glutamine synthetase, thereby regulating nitrogen assimilation. We have generated
      glnE mutant strains that are unable to adenylylate glutamine synthetase (GS).
      Surprisingly, the activity of GS was lower in the mutants than in the wild type,
      even when grown in nitrogen-fixing conditions. Our results support the proposal
      that R. rubrum can only cope with the absence of an adenylylation system in the
      presence of lowered GS expression or activity. In general terms, this report also
      provides further support for the central role of GS in bacterial metabolism.

PMID- 19761832
TI  - Antibody responses against NY-ESO-1 and HER2 antigens in patients vaccinated with
      combinations of cholesteryl pullulan (CHP)-NY-ESO-1 and CHP-HER2 with OK-432.
AB  - Combination vaccines of the NY-ESO-1 protein complexed with cholesteryl pullulan
      (CHP), CHP-NY-ESO-1, and the truncated 146HER2 protein with CHP, CHP-HER2, were
      subcutaneously administered with the immuno-adjuvant OK-432 to eight esophageal
      cancer patients. Vaccination was well-tolerated. NY-ESO-1- and HER2-specific
      antibody responses were analyzed using the patients' sera and samples from
      previous single CHP-NY-ESO-1 or CHP-HER2 vaccine trial. The responses to NY-ESO-1
      in the combination vaccine study were comparable to the single vaccine. For
      responses to HER2, there were fewer antibody responses in the combination
      vaccines. Although there were marked individual variations in the antibody
      responses to the NY-ESO-1 and HER2 antigens, the reaction patterns to these
      antigens were comparable within each patient. Antibodies to OK-432 were not
      augmented. Protein cancer vaccines targeting multiple antigens are feasible.

PMID- 19761833
TI  - Plasma fibrinogen levels after vaccination with a native outer membrane vesicle
      vaccine for Neisseria meningitidis.
AB  - Several studies have shown plasma fibrinogen increases following some
      vaccinations, but the specific triggers and the kinetics of this response are not
      well understood. We conducted a phase I trial of an outer membrane vesicle
      vaccine for Neisseria meningitidis. Plasma fibrinogen was measured on days 0, 2
      and 14 following each of 3 doses. The highest dose of vaccine was associated with
      the greatest increase in fibrinogen at day 2, which decreased by day 14. The
      first vaccination caused a greater increase than either subsequent vaccination.
      These transient increases in fibrinogen are comparable to what occurs with upper
      respiratory infections and have not been demonstrated to represent an increased
      risk of adverse vascular events.

PMID- 19761834
TI  - Immunization with HSV-1 glycoprotein C prevents immune evasion from complement
      and enhances the efficacy of an HSV-1 glycoprotein D subunit vaccine.
AB  - Herpes simplex virus type 1 (HSV-1) glycoprotein C (gC-1) binds complement
      component C3b and inhibits complement-mediated immunity. HSV-1 glycoprotein D (gD
      1) is a potent immunogen and a candidate antigen for a subunit vaccine. We
      evaluated whether combined immunization with gD-1 and gC-1 provides better
      protection against challenge than gD-1 alone based on antibodies to gC-1
      preventing HSV-1-mediated immune evasion. IgG purified from mice immunized with
      gC-1 blocked C3b binding to gC-1 and greatly increased neutralization by gD-1 IgG
      in the presence of complement. Passive transfer of gC-1 IgG protected complement
      intact mice against HSV-1 challenge but not C3 knockout mice, indicating that gC
      1 antibody activity in vivo is complement-dependent. Immunizing mice with gD-1
      and gC-1 provided better protection than gD-1 alone in preventing zosteriform
      disease and infection of dorsal root ganglia. Therefore, gC-1 immunization
      prevents HSV-1 evasion from complement and enhances the protection provided by gD
      1 immunization.

PMID- 19761835
TI  - Priorities in research and development of vaccines against Plasmodium vivax
      malaria.
AB  - The WHO Initiative for Vaccine Research (IVR) Malaria Vaccine Advisory Committee
      (MALVAC) provides advice to WHO on priorities in malaria vaccine research and
      development (R&D). This document summarizes a MALVAC scientific consultation of
      leading vaccine scientists on priorities in Plasmodium vivax vaccine R&D. The
      meeting discussed recent advances and key challenges in addressing identified
      gaps in knowledge. Major areas of discussion included disease burden estimates,
      clinical disease spectrum definitions, potential target product profiles and
      immunological and clinical research needed to better inform antigen selection and
      vaccine design. The need for further development of the human challenge model for
      P. vivax vaccines and specific considerations for conduct of field trials with P.
      vivax vaccines was outlined. This report summarizes the discussion and
      conclusions of the consultation, with recommendations for priority targeted
      research.

PMID- 19761836
TI  - Improved influenza vaccination in the skin using vaccine coated microneedles.
AB  - Easy and effective vaccination methods could reduce mortality rates and morbidity
      due to vaccine-preventable influenza infections. In this study, we examined the
      use of microneedle patches to increase patient coverage through possible self
      administration and enhance vaccine immunogenicity by targeted delivery to skin.
      We carried out a detailed study of protective immune responses after a single
      influenza vaccination to the skin of mice with a novel microneedle patch designed
      to facilitate simple and reliable vaccine delivery. Skin vaccination with
      inactivated virus-coated microneedles provided superior protection against lethal
      challenge compared to intramuscular injection as evidenced by effective virus
      clearance in lungs. Detailed immunologic analysis suggests that induction of
      virus neutralizing antibodies as well as enhanced anamnestic humoral and cellular
      responses contributed to improved protection by microneedle vaccination to the
      skin. These findings suggest that vaccination in the skin using a microneedle
      patch can improve protective immunity, and simplify delivery of influenza and
      possibly other vaccines.

PMID- 19761837
TI  - Humoral and cellular immune responses to split-virion H5N1 influenza vaccine in
      young and elderly adults.
AB  - We evaluated the humoral and cellular immunogenicity of adjuvanted and non
      adjuvanted H5N1 influenza vaccine in two groups of 300 adults: aged 18-60 and >60
      years in a randomized, open-label, uncontrolled phase 2 trial. Participants
      received two injections (D0, D21) of 7.5 microg hemagglutinin without adjuvant or
      30 microg with aluminum hydroxide adjuvant. Antibody responses and cytokine
      secretion were assessed before and after vaccination. Excluding the 6/300 non
      elderly and 47/300 elderly participants with pre-existing antibodies, geometric
      mean titers (dil(-1)) on D42 were higher with 30 microg+Ad and were comparable
      between age groups. Participants with pre-existing antibodies responded strongly
      to the first vaccination (GMTs in the range 147-228 on D21). Vaccination
      increased both Th1 and Th2 T-cell responses. The predominantly Th1 profile
      observed before vaccination was unaffected by vaccination. H5N1 influenza vaccine
      is no less immunogenic in elderly adults than in younger adults and, due to a
      higher proportion non-naive elderly, immunogenicity was higher in this latter
      group.

PMID- 19761838
TI  - Immune responses following one and two doses of the reformulated, bivalent,
      killed, whole-cell, oral cholera vaccine among adults and children in Kolkata,
      India: a randomized, placebo-controlled trial.
AB  - Immune responses after one and two doses of the reformulated killed oral cholera
      vaccine were measured in a double-blind, randomized, placebo-controlled trial of
      77 adults aged 18-40 years and 77 children aged 1-17 years residing in Kolkata,
      India. 65% of adults and 87% of children and 46% of adults and 82% of children
      exhibited a > or =4-fold rise in serum Vibrio cholerae O1 vibriocidal antibody
      titers from baseline following dose 1 and 2, respectively. Responses to V.
      cholerae O139 were less pronounced but followed a similar pattern. We demonstrate
      that in a cholera-endemic area, the vaccine elicited vibriocidal responses after
      a single-dose of the vaccine.

PMID- 19761839
TI  - Replication of rubella vaccine population genetic studies: validation of HLA
      genotype and humoral response associations.
AB  - Purported genetic associations found in population studies require validation for
      confirmation. We previously reported rubella vaccine-induced immune responses and
      HLA associations in 346 adolescents, age 12-18 years (1st cohort), following two
      doses of a rubella-containing vaccine. We sought to replicate the associations
      discovered in that work by verifying these associations in a new cohort of 396
      subjects, age 11-19 years (2nd cohort), all having had two doses of a rubella
      containing vaccine. We found that B*2705 (median 1st cohort 20.9 IU/ml, p=0.028;
      2nd cohort 20.5 IU/ml, p=0.001) and DPA1*0201 (median 1st cohort 32.5 IU/ml,
      p=0.048; 2nd cohort 25.8 IU/ml, p=0.025) alleles were consistently associated
      with lower rubella-induced antibodies. Further, DPB1*0401 (median 1st cohort 43.5
      IU/ml, p=0.021; 2nd cohort 36.2 IU/ml, p=0.002) alleles were associated with
      higher antibody levels in both populations. The association of DRB1*04-DQB1*03
      DPB1*03 (mean 1st cohort 25.2 IU/ml, p=0.011; 2nd cohort 21.4 IU/ml, p=0.032) and
      DRB1*15/16-DQB1*06-DPB1*03 (1st cohort 16.3 IU/ml, p=0.043; 2nd cohort 19.1
      IU/ml, p=0.023) haplotypes with lower rubella-specific antibodies was observed in
      both studies. This study provides confirmatory evidence for an association
      between specific class I and II HLA markers and haplotypes with rubella vaccine
      induced humoral responses and lends further weight to their influence on rubella
      immune responses.

PMID- 19761840
TI  - Bacterially expressed recombinant envelope protein domain III of Japanese
      encephalitis virus (rJEV-DIII) elicits Th1 type of immune response in BALB/c
      mice.
AB  - Japanese encephalitis is a major cause of encephalitis in Asia. Cases occur
      largely in rural areas of the South and East Asian region resulting in
      significant morbidity and mortality. Multiple vaccines exist to control Japanese
      encephalitis, but all suffer from problems. Envelope protein domain III of
      Japanese encephalitis virus is involved in binding to host receptors and it
      contains specific epitopes that elicit virus-neutralizing antibodies. Earlier,
      the protective efficacy of domain III has been evaluated in mice by some
      researchers, but these studies are lacking in explanation of humoral and cellular
      immune responses. We have earlier reported cloning, expression, purification and
      in vitro refolding of Japanese encephalitis virus envelope protein domain III
      (rJEV-DIII). Ninety percent JEV is neutralized when the serum against refolded
      rJEV-DIII is used at a dilution of 1:80. In the present study, we have evaluated
      the immunomodulatory potential of refolded rJEV-DIII protein in BALB/c mice with
      Freunds complete/incomplete adjuvants. Mice were tested for humoral immune
      response by ELISA. Cell-mediated immune response was tested by lymphocyte
      proliferation assay and cytokine profiling. The rJEV-DIII generated high IgG
      antibody and its isotypes (IgG2a and IgG3) and induced significant expression of
      INF-gamma and IL-2 cytokines. The rJEV-DIII induced significant
      lymphoproliferation of splenocytes. In conclusion rJEV-DIII induced Th1 type of
      immune response which plays an important role in protection for intracellular
      pathogens.

PMID- 19761841
TI  - Telemetric analysis to detect febrile responses in mice following vaccination
      with a live-attenuated virus vaccine.
AB  - Non-human primates (NHP) are considered to be the most appropriate model for
      predicting how humans will respond to many infectious diseases. Due to ethical
      and monetary concerns associated with the use of NHP, rodent models that are as
      predictive of responses likely to be seen in human vaccine recipients are
      warranted. Using implanted telemetry devices, body temperature and activity were
      monitored in inbred and outbred mouse strains following administration of the
      live-attenuated vaccine for Venezuelan equine encephalitis virus (VEEV), V3526.
      Following analysis of individual mouse data, only outbred mouse strains showed
      changes in diurnal temperature and activity profiles following vaccination.
      Similar changes were observed following VEEV challenge of vaccinated outbred
      mice. From these studies, we conclude, outbred mouse strains implanted with
      telemeters are a sensitive model for predicting responses in humans following
      vaccination.

PMID- 19761842
TI  - Pharmacokinetics of ipriflavone and its two metabolites, M1 and M5, after the
      intravenous and oral administration of ipriflavone to rat model of diabetes
      mellitus induced by streptozotocin.
AB  - Ipriflavone was reported to be primarily metabolized via hepatic cytochrome P450
      (CYP) 1A1/2 and 2C11 in male Sprague-Dawley rats. The protein expression and/or
      mRNA levels of hepatic CYP1A subfamily and 2C11 was reported to be increased and
      decreased, respectively, in diabetic rats induced by streptozotocin (DMIS rats).
      Thus, the pharmacokinetic parameters of ipriflavone and its two metabolites, M1
      and M5, were compared after the i.v. (20mg/kg) and p.o. (200mg/kg) administration
      of ipriflavone to control and DMIS rats. After both i.v. and p.o. administration
      of ipriflavone to DMIS rats, the AUCs of ipriflavone were significantly smaller
      (by 31.7% and 34.2% for i.v. and p.o. administration, respectively) than
      controls. The faster Cl(nr) (smaller AUC) of i.v. ipriflavone could have been due
      to the faster hepatic Cl(int) (because of an increase in the protein expression
      and/or mRNA level of hepatic CYP1A subfamily) and the faster hepatic blood flow
      rate than controls. The smaller AUC of p.o. ipriflavone in DMIS rats could have
      mainly been due to the faster intestinal Cl(int) (because of an increase in the
      intestinal CYP1A subfamily) than controls.

PMID- 19761843
TI  - Size-dependent release of fluorescent macromolecules and nanoparticles from
      radically cross-linked hydrogels.
AB  - Hydrogels play an important role in drug delivery and tissue engineering
      applications due to their excellent biocompatibility and their variable
      mechanical and physical properties, which allow their optimization for many
      different aspects of the intended use. In this study, we examined the suitability
      of poly(ethylene glycol) (PEG)-based hydrogels as release systems for nanometer
      sized drugs or drug carriers, like nanoparticles, using the radically cross
      linkable oligo(poly(ethylene glycol)fumarate) (OPF) together with two cross
      linking agents. Different fluorescent nanoparticulate probes with respect to size
      and physical structure were incorporated in the cross-linked hydrogels, and the
      obtained release profiles were correlated with the physical properties and the
      chemical structure of the gels, indicating a strong dependence of the release on
      the chosen PEG prepolymers. The prepared hydrogels were characterized by
      oscillatory rheometry and swelling experiments. Release experiments as well as
      diffusion measurements using fluorescence recovery after photobleaching showed
      the great potential of this type of hydrogels for the preparation of adjustable
      release systems by altering the molecular weights of the used PEG molecules.

PMID- 19761844
TI  - Human bone marrow-derived stromal cells show highly efficient stress-resistant
      adipogenesis on denatured collagen IV matrix but not on its native counterpart:
      implications for obesity.
AB  - Collagen IV is the major matrix component associated with differentiating
      adipocytes in adipose tissues, and the understanding of its contribution in
      adipogenic differentiation could be important for elucidation of mechanisms and
      processes driving the obesity. Therefore, in the light of our previous findings
      of differential effects of structural conformation of collagen I matrix on
      differentiation of bone marrow stromal cells, we investigated whether similar
      phenomenon occurs on collagen IV matrix in native and denatured structural
      states. The results of the present study show that native collagen IV is
      unsupportive of adipogenic differentiation and very little if any adipogenesis
      occurs on this matrix in the presence of adipogenic stimuli. In sharp contrast to
      native collagen IV, the same matrix in denatured structural state drives highly
      efficient adipogenic differentiation suggesting that it might be the major driver
      of adipogenesis in adipose tissues and that the ratio of native to denatured
      matrix might regulate the intensity of adipogenesis and possibly underlies the
      obesity. In contrast to observations that adipogenesis on denatured collagen I
      (collagen I is the major matrix component in musculoskeletal tissues) is
      suppressed by stress, adipogenesis on denatured collagen IV appears to be stress
      resistant suggesting an explanation for the observed ineffectiveness of physical
      exercise, i.e. mechanical stress, in the reduction of adipose tissues. The
      obesity was shown to be associated with overproduction of MMPs and decline in
      levels of TIMPs. Such a shift in MMP/TIMP balance was considered a consequence of
      the pathology. In the light of the present study, however, this shift might
      constitute the primary source of the decease. The findings of the present study
      suggest strategies for the treatment of obesity, raise significant questions and
      indicate directions for further experimentation.

PMID- 19761845
TI  - A novel functional role of iduronate-2-sulfatase in zebrafish early development.
AB  - Sulfated glycosaminoglycan chains of extracellular matrix and cell membrane
      tethered proteoglycans exert specific cellular functions by interacting with a
      broad spectrum of morphogens and growth factors. In humans, a congenital impaired
      catabolism of sulfated glycosaminoglycans is associated with severe metabolic
      disorders. Here, we report on the identification and characterization of a
      zebrafish iduronate sulfatase orthologue. By knocking down its function with
      antisense morpholino oligos, we demonstrate that iduronate sulfatase plays a
      critical role during early vertebrate development and its downregulation may be
      responsible for severe developmental defects, including a misshapen trunk and
      abnormal craniofacial cartilages. We show that the altered cartilage patterning
      is mediated by depauperation of sox10-expressing neural crest cell precursors.
      Through the application of a transactivation reporter assay, we also provide a
      molecular proof that increased TGFbeta (Transforming Growth Factor beta)
      signalling is tightly associated with downregulation of iduronate sulfatase
      function. Our results provide an insight into the early biological impairments
      underlying the Hunter syndrome and suggest the use of zebrafish as a novel tool
      to better understand lysosomal storage disorder pathogenesis.

PMID- 19761846
TI  - Genetic modifiers of degeneration in the cathepsin D deficient Drosophila model
      for neuronal ceroid lipofuscinosis.
AB  - Neuronal ceroid lipofuscinoses (NCLs) are pediatric, neurodegenerative, lysosomal
      storage disorders. Mutations in cathepsin D result in the most severe, congenital
      form of NCLs. We have previously generated a cathepsin D deficient Drosophila
      model, which exhibits the key features of NCLs: progressive intracellular
      accumulation of autofluorescent storage material and modest neurodegeneration in
      the brain areas related to visual functions. Here we extend the phenotypic
      characterization of cathepsin D deficient Drosophila and report that modest
      degenerative changes are also present in their retinae. Furthermore, by utilizing
      this phenotype, we examined the possible effect of 17 candidate modifiers,
      selected based on the results from other cathepsin D deficiency models. We found
      enhancers of this phenotype that support the involvement of endocytosis-, lipid
      metabolism- and oxidation-related factors in the cathepsin D deficiency induced
      degeneration. Our results warrant further investigation of these mechanisms in
      the pathogenesis of cathepsin D deficiency.

PMID- 19761847
TI  - Cloning and molecular characterization of lycC1INH genes in large yellow croaker
      (Pseudosciaena crocea).
AB  - Complement component 1 inhibitor (C1INH) is a crucial protein in controlling
      activation of many plasma mediator pathways and can directly interact with Gram
      negative bacteria. The full-length cDNA of lycC1INH gene was identified from the
      large yellow croaker. It is of 2046 nucleotides (nt) encoding a protein of 599
      amino acids, with a 5'-untranslated region of 99 nt and a 3'-untranslated region
      of 147 nt including the poly (A) tail. The deduced protein contains a C-terminal
      serpin (serine protease inhibitor) domain, and two N-terminus immunoglobulin
      domains without significant homology to other species. Western blot analysis of
      the protein expression showed that the expression of lycC1INH was obviously up
      regulated in liver, spleen and head kidney of the fish challenged by attenuated
      live Vibrio anguillarum strain. This indicated that lycC1INH might be involved in
      the immune response of large yellow croaker to bacterial challenge.

PMID- 19761848
TI  - Optimal region of the putamen for image-guided convection-enhanced delivery of
      therapeutics in human and non-human primates.
AB  - Optimal results in the direct brain delivery of brain therapeutics such as growth
      factors or viral vector into primate brain depend on reproducible distribution
      throughout the target region. In the present study, we retrospectively analyzed
      MRI of 25 convection-enhanced delivery (CED) infusions with MRI contrast into the
      putamen of non-human primates (NHP). Infused volume (V(i)) was compared to total
      volume of distribution (V(d)) versus V(d) within the target putamen. Excellent
      distribution of contrast agent within the putamen was obtained in eight cases
      that were used to define an optimal target volume or "green" zone. Partial or
      poor distribution with leakage into adjacent anatomical structures was noted in
      17 cases, defining "blue" and "red" zones, respectively. Quantitative containment
      (99+/-1%) of infused gadoteridol within the putamen was obtained when the cannula
      was placed in the green zone, 87+/-3% in the blue zone and 49+/-0.05% in the red
      zone. These results were used to determine a set of 3D stereotactic coordinates
      that define an optimal site for putaminal infusions in NHP and human putamen. We
      conclude that cannula placement and definition of optimal (green zone)
      stereotactic coordinates have important implications in ensuring effective
      delivery of therapeutics into the putamen utilizing routine stereotactic MRI
      localization procedures and should be considered when local therapies such as
      gene transfer or protein administration are being translated into clinical
      therapy.

PMID- 19761849
TI  - Functional neural correlates of fluid and crystallized analogizing.
AB  - The main aim of this study was to characterize neural correlates of analogizing
      as a cognitive contributor to fluid and crystallized intelligence. In a previous
      fMRI study which employed fluid analogy letter strings as criteria in a multiple
      plausibility design (Geake and Hansen, 2005), two frontal ROIs associated with
      working memory (WM) load (within BA 9 and BA 45/46) were identified as regions in
      which BOLD increase correlated positively with a crystallized measure of (verbal)
      IQ. In this fMRI study we used fluid letter, number and polygon strings to
      further investigate the role of analogizing in fluid (transformation string
      completion) and non fluid or crystallized (unique symbol counting) cognitive
      tasks. The multi stimulus type (letter, number, polygon) design of the analogy
      strings enabled investigation of a secondary research question concerning the
      generalizability of fluid analogizing at a neural level. A selective psychometric
      battery, including the Raven's Progressive Matrices (RPM), measured individual
      cognitive abilities. Neural activations for the effect of task-fluid analogizing
      (string transformation plausibility) vs. crystallized analogizing (unique symbol
      counting)-included bilateral frontal and parietal areas associated with WM load
      and fronto parietal models of general intelligence. Neural activations for
      stimulus type differences were mainly confined to visually specific posterior
      regions. ROI covariate analyses of the psychometric measures failed to find
      consistent co-relationships between fluid analogizing and the RPM and other
      subtests, except for the WAIS Digit Symbol subtest in a group of bilateral
      frontal cortical regions associated with the maintenance of WM load. Together,
      these results support claims for separate developmental trajectories for fluid
      cognition and general intelligence as assessed by these psychometric subtests.

PMID- 19761850
TI  - Brain correlates of risky decision-making.
AB  - Understanding the neurocognitive basis of risk-taking behavior is an important
      issue, especially in economic decision-making. Classical behavioral studies have
      shown that risk-attitude changes across different contexts, but little is so far
      known about the brain correlates of processing of outcomes across such context
      shifts. In this study, EEG was recorded while subjects performed a gambling task.
      Participants could choose between a risky and a safer option, within two
      different contexts: one in which options yielded gains and losses of the same
      magnitude (Zero Expected Value context) and another in which gains were larger
      than losses (Positive Expected Value context). Based on their risk-attitude, two
      groups were compared: subjects who are risk-seekers in the zero Expected Value
      context (Zero-Oriented group) and subjects who are risk-seekers in the positive
      Expected Value condition (Positive-Oriented group). The Feedback Related
      Negativity (FRN) reflects this distinction, with each group being insensitive to
      magnitude of outcomes in the condition in which they were risk-prone. P300
      amplitude mirrored the behavioral results, with larger amplitudes in the
      condition in which each group showed a higher risk-tendency. Source analyses
      highlighted the involvement of posterior cingulate cortex in risky decision
      making. Taken together, the findings make a contribution to the clarification of
      the neurocognitive substrates of risky decision-making.

PMID- 19761851
TI  - A neural measure of behavioral engagement: task-residual low-frequency blood
      oxygenation level-dependent activity in the precuneus.
AB  - Brain imaging has provided a useful tool to examine the neural processes
      underlying human cognition. A critical question is whether and how task
      engagement influences the observed regional brain activations. Here we
      highlighted this issue and derived a neural measure of task engagement from the
      task-residual low-frequency blood oxygenation level-dependent (BOLD) activity in
      the precuneus. Using independent component analysis, we identified brain regions
      in the default circuit - including the precuneus and medial prefrontal cortex
      (mPFC) - showing greater activation during resting as compared to task residuals
      in 33 individuals. Time series correlations with the posterior cingulate cortex
      as the seed region showed that connectivity with the precuneus was significantly
      stronger during resting as compared to task residuals. We hypothesized that if
      the task-residual BOLD activity in the precuneus reflects engagement, it should
      account for a certain amount of variance in task-related regional brain
      activation. In an additional experiment of 59 individuals performing a stop
      signal task, we observed that the fractional amplitude of low-frequency
      fluctuation (fALFF) of the precuneus but not the mPFC accounted for approximately
      10% of the variance in prefrontal activation related to attentional monitoring
      and response inhibition. Taken together, these results suggest that task-residual
      fALFF in the precuneus may be a potential indicator of task engagement. This
      measurement may serve as a useful covariate in identifying motivation-independent
      neural processes that underlie the pathogenesis of a psychiatric or neurological
      condition.

PMID- 19761852
TI  - Time-resolved functional 1H MR spectroscopic detection of glutamate concentration
      changes in the brain during acute heat pain stimulation.
AB  - Non-invasive in vivo detection of cortical neurotransmitter concentrations and
      their changes in the presence of pain may help to better understand the
      biochemical principles of pain processing in the brain. In the present study
      acute heat pain related changes of the excitatory neurotransmitter glutamate were
      investigated in the anterior insular cortex of healthy volunteers by means of
      time-resolved functional proton magnetic resonance spectroscopy ((1)H-MRS).
      Dynamic metabolite changes were estimated with a temporal resolution of five
      seconds by triggering data acquisition to the time course of the cyclic stimulus
      application. An overall increase of glutamate concentration up to 18% relative to
      the reference non-stimulus condition was observed during the application of short
      pain stimuli.

PMID- 19761853
TI  - Sleep deprivation and its effects on object-selective attention.
AB  - Sleep deprivation (SD) affects attention but it is an open question as to whether
      all subtypes of attention are similarly affected. We investigated the effects of
      24 h of total SD on object-selective attention. 26 healthy, young adults viewed
      quartets of alternating faces or place scenes and performed selective judgments
      on faces only, scenes only or both faces and scenes. Volunteers underwent fMRI
      following a normal night of sleep and again following approximately 24 h of total
      sleep deprivation in a counterbalanced fashion. Sleep deprivation resulted in
      slower and less accurate picture classification as well as poorer recognition
      memory for scenes. Attention strongly modulated activation in the Parahippocampal
      Place Area (PPA). Task-related activation in the fronto-parietal cortex and PPA
      was reduced in SD, but the relative modulation of PPA activation by attention was
      preserved. Psychophysiological interaction between the left intra-parietal sulcus
      and the PPA that was clearly present after a normal night of sleep was reduced
      below threshold following SD suggesting that PPI may be a more sensitive method
      of detecting change in selective attention. Sleep deprivation may affect object
      selective attention in addition to exerting a task-independent deficit in
      attention.

PMID- 19761854
TI  - Polyphyly of the Zaprionus genus group (Diptera: Drosophilidae).
AB  - The Zaprionus genus group comprises three drosophilid genera (Zaprionus,
      Phorticella and Samoaia) that are thought to be related to the Drosophila
      immigrans species group. We revised the phylogenetic relationships among the
      three genera and their placement within the subfamily Drosophilinae using one
      mitochondrial (COII) and one nuclear (Amyrel) gene. The Bayesian tree inferred
      from concatenated amino acid sequences of the two genes strongly suggests the
      polyphyly of the Zaprionus genus group and of each of the genera Zaprionus and
      Phorticella. Paraphyly of the D.immigrans species group was also shown here; the
      quadrilineata subgroup formed the sister clade to the genus Samoaia. These
      results suggest the necessity of taxonomic revisions for some relevant genera and
      species groups included within the genus Drosophila.

PMID- 19761855
TI  - Phylogeny, biogeography, and electric signal evolution of Neotropical knifefishes
      of the genus Gymnotus (Osteichthyes: Gymnotidae).
AB  - The Neotropical knifefish genus Gymnotus is the most broadly distributed and the
      most diverse (34+species) gymnotiform genus. Its wide range includes both Central
      and South American drainages, including the Amazon, Orinoco, and La Plata Basins.
      Like all gymnotiforms, Gymnotus species produce weak electric fields for both
      navigation and communication, and these fields exhibit interspecific variation in
      electric waveform characteristics. Both biogeography and electric signal
      evolution can profitably be analyzed in a phylogenetic context. Here, we present
      a total evidence phylogeny for 19 Gymnotus species based on data from the
      mitochondrial cytochrome b and 16S genes (1558 bp), the nuclear RAG2 gene (1223
      bp), and 113 morphological characters. Our phylogenetic hypothesis resolves five
      distinct Gymnotus lineages. In a previous morphology-based analysis, the Central
      American Gymnotus cylindricus lineage was hypothesized as the sister group to all
      other Gymnotus species. In our analysis, the G. cylindricus lineage is nested
      within South American species, and molecular age estimates support a relatively
      recent origin for the clade in Central America. Phylogenetic optimization of
      electric signal waveforms indicate that the ancestral state in Gymnotus is a
      multiphasic (4+phases of alternating polarity) condition, and independent phase
      loss has occurred in multiple lineages. Gymnotus is a model group for
      understanding Neotropical diversification and the evolution of communication at a
      continental scale.

PMID- 19761856
TI  - Estimating sample sizes for DNA barcoding.
AB  - Sample size has long been one of the basic issues since the start of the DNA
      barcoding initiative and the global biodiversity investigation. As a contribution
      to resolving this problem, we propose a simple resampling approach to estimate
      several key sampling sizes for a DNA barcoding project. We illustrate our
      approach using both structured populations simulated under coalescent and real
      species of skipper butterflies. We found that sample sizes widely used in DNA
      barcoding are insufficient to assess the genetic diversity of a species,
      population structure impacts the estimation of the sample sizes, and hence will
      bias the species identification potentially.

PMID- 19761857
TI  - Remarkably low mtDNA control region diversity in an abundant demersal fish.
AB  - Cape hake, Merluccius paradoxus, is a valuable commercially exploited demersal
      species. Using the 5' mtDNA control region we show that 96% of 1013 fishes
      sampled over a three-year period share one of two dominant haplotypes; 19
      haplotypes were recovered in total, suggesting a genetically homogenous
      population of fish. Accordingly, haplotype and nucleotide diversities are low (h
      = 0.53, pi = 0.0014); an asymptotic haplotype accumulation curve suggests that
      few additional haplotypes exist. Comparing h and pi with other fish species shows
      that M. paradoxus and other southern African fish species have remarkably low
      genetic diversity values compared with other global marine fishes. Despite low
      genetic variability, frequency differences among M. paradoxus haplotypes suggest
      weakly structured populations between Namibia and South Africa. However, given
      the remarkably homogeneous mtDNA population genetic structure between fishes
      sampled along 1800 km, it is clear that faster evolving markers such a
      microsatellites are also needed before inferences can be made regarding stock
      identification and management of this species.

PMID- 19761858
TI  - Fast evolution of the retroprocessed mitochondrial rps3 gene in Conifer II and
      further evidence for the phylogeny of gymnosperms.
AB  - The popular view that plant mitochondrial genome evolves slowly in sequence has
      been recently challenged by the extraordinarily high substitution rates of mtDNA
      documented mainly from several angiosperm genera, but high substitution rate
      acceleration accompanied with great length variation has been very rarely
      reported in plant mitochondrial genes. Here, we studied evolution of the
      mitochondrial rps3 gene that encodes the ribosomal small subunit protein 3 and
      found a dramatically high variation in both length and sequence of an exon region
      of it in Conifer II. A sequence comparison between cDNA and genomic DNA showed
      that there are no RNA editing sites in the Conifer II rps3 gene. Southern
      blotting analyses of the total DNA and mtDNA, together with the real-time PCR
      analysis, showed that rps3 exists as a single mitochondrial locus in gymnosperms.
      It is very likely that the Conifer II rps3 gene has experienced retroprocessing,
      i.e., the re-integration of its cDNA into the mitochondrial genome, followed by
      an evolutionary acceleration due to the intron loss. In addition, the
      phylogenetic analysis of rps3 supports the sister relationship between conifers
      and Gnetales. In particular, the monophyly of conifer II is strongly supported by
      the shared loss of two rps3 introns. Our results also indicate that the
      mitochondrial gene tree would be affected in topology when the "edited" paralogs
      are analyzed together with their genomic sequences.

PMID- 19761859
TI  - Does the olfactory cue activate the same brain network during aging in the rat
      after taste potentiated odor aversion retrieval?
AB  - Depending on the brain networks involved, aging is not accompanied by a general
      decrease in learning and memory capabilities. We demonstrated previously that
      learning and retrieval of taste potentiated odor aversion (TPOA) is preserved,
      and even slightly improved, in senescent rats showing some memory deficiencies in
      cognitive tasks (Dardou, Datiche, & Cattarelli, 2008). TPOA is a particular
      behavior in which the simultaneous presentation of odor and taste cues followed
      by a delayed visceral illness leads to a robust aversion towards both conditioned
      stimuli, which permits diet selection and animal survival. The present experiment
      was performed in order to investigate the stability or the evolution of the brain
      network underlying TPOA retrieval during aging. By using immunocytochemical
      detection of Fos and Egr1 proteins we mapped the cerebral activation induced by
      TPOA retrieval elicited by the odor presentation in the young, the adult and the
      senescent rats. The pattern of brain activation changed and the number of
      activated areas decreased with age. Nevertheless, the piriform cortex and the
      basolateral amygdala nucleus were always activated and seemed essential for TPOA
      retrieval. The hippocampus and the neocortical areas could have different
      implications in TPOA memory in relation to age. The patterns of expression of Fos
      and Egr1 were different, suggesting their differential involvement in TPOA
      retrieval. Data are discussed according to the possible roles of the brain areas
      studied and a model of schematic brain network subtending TPOA retrieval induced
      by the odor cue is proposed.

PMID- 19761860
TI  - The medial prefrontal cortex and memory of cue location in the rat.
AB  - We developed a single-trial cue-location memory task in which rats experienced an
      auditory cue while exploring an environment. They then recalled and avoided the
      sound origination point after the cue was paired with shock in a separate
      context. Subjects with medial prefrontal cortical (mPFC) lesions made no such
      avoidance response, but both lesioned and control subjects avoided the cue itself
      when presented at test. A follow up assessment revealed no spatial learning
      impairment in either group. These findings suggest that the rodent mPFC is
      required for incidental learning or recollection of the location at which a
      discrete cue occurred, but is not required for cue recognition or for allocentric
      spatial memory.

PMID- 19761861
TI  - Intracranial self-stimulation recovers learning and memory capacity in
      basolateral amygdala-damaged rats.
AB  - We studied the capacity of post-training intracranial self-stimulation (SS) to
      reverse or ameliorate learning and memory impairments caused by amygdala damage
      in rats. A first experiment showed that lesions of the basolateral amygdala (BLA)
      slow down acquisition of two-way active avoidance conditioning (2wAA). In a
      second experiment we observed that a post-training SS treatment administered
      immediately after each 2wAA conditioning session is able to completely reverse
      the disruptive effects of the BLA lesions, and the facilitative effect lasts for
      10days. A third experiment allowed us to differentiate the strong recuperative
      effects of the SS treatment from the slight effect caused by overtraining the
      same conditioning response. We concluded that SS is able to counteract the
      behavioral deficit induced by BLA damage, probably by activating alternative
      undamaged brain structures related to learning and memory, such as the
      hippocampus.

PMID- 19761862
TI  - Cycloheximide produces amnesia for extinction and reconsolidation in an
      appetitive odor discrimination task in rats.
AB  - A considerable literature has shown deficits in memory resulting from the
      administration of protein synthesis inhibitors; however, most of the past
      literature in this field has focused on acquisition of new memory using
      aversively-motivated tasks. The effect of protein synthesis inhibition on
      appetitive learning and memory as well as extinction is less clear. The present
      study employed an appetitive odor discrimination paradigm to examine the effects
      of acute cycloheximide administration (1mg/kg) on reconsolidation and extinction.
      Male, Long-Evans adult rats were trained to discriminate between two odors (i.e.,
      cocoa and cinnamon) and then received extinction trials following an
      intraperitoneal injection of cycloheximide or vehicle. Twenty-four hours later,
      rats were tested via one non-reinforced test trial. Results showed amnesia for
      extinction as well as original training (i.e., correct odor choice) in
      cycloheximide-injected rats in this appetitive task, while vehicle-injected
      controls showed good memory for extinction. These data add to a growing
      literature showing the importance of protein synthesis inhibition for extinction
      and reconsolidation in appetitive learning and memory.

PMID- 19761864
TI  - High-dose chemotherapy with autotransplantation in AL amyloidosis: a flawed meta
      analysis.

PMID- 19761866
TI  - Immortality and the base of multicellular life: Lessons from cnidarian stem
      cells.
AB  - Cnidarians are phylogenetically basal members of the animal kingdom (>600 million
      years old). Together with plants they share some remarkable features that cannot
      be found in higher animals. Cnidarians and plants exhibit an almost unlimited
      regeneration capacity and immortality. Immortality can be ascribed to the asexual
      mode of reproduction that requires cells with an unlimited self-renewal capacity.
      We propose that the basic properties of animal stem cells are tightly linked to
      this archaic mode of reproduction. The cnidarian stem cells can give rise to a
      number of differentiated cell types including neuronal and germ cells. The
      genomes of Hydra and Nematostella, representatives of two major cnidarian classes
      indicate a surprising complexity of both genomes, which is in the range of
      vertebrates. Recent work indicates that highly conserved signalling pathways
      control Hydra stem cell differentiation. Furthermore, the availability of genomic
      resources and novel technologies provide approaches to analyse these cells in
      vivo. Studies of stem cells in cnidarians will therefore open important insights
      into the basic mechanisms of stem cell biology. Their critical phylogenetic
      position at the base of the metazoan branch in the tree of life makes them an
      important link in unravelling the common mechanisms of stem cell biology between
      animals and plants.

PMID- 19761865
TI  - Regulation of convergence and extension movements during vertebrate gastrulation
      by the Wnt/PCP pathway.
AB  - Vertebrate gastrulation entails massive cell movements that establish and shape
      the germ layers. During gastrulation, the individual cell behaviors are strictly
      coordinated in time and space by various signaling pathways. These pathways
      instruct the cells about proliferation, shape, fate and migration into proper
      location. Convergence and extension (C&E) movements during vertebrate
      gastrulation play a major role in the shaping of the embryonic body. In
      vertebrates, the Wnt/Planar Cell Polarity (Wnt/PCP) pathway is a key regulator of
      C&E movements, essential for several polarized cell behaviors, including directed
      cell migration, and mediolateral and radial cell intercalation. However, the
      molecular mechanisms underlying the acquisition of Planar Cell Polarity by highly
      dynamic mesenchymal cells engaged in C&E are still not well understood. Here we
      review new evidence implicating the Wnt/PCP pathway in specific cell behaviors
      required for C&E during zebrafish gastrulation, in comparison to other
      vertebrates. We also discuss findings on the molecular regulation and the
      interaction of the Wnt/PCP pathway with other signaling pathways during
      gastrulation movements.

PMID- 19761867
TI  - Etoposide, cadmium chloride, benzo[a]pyrene, cyclophosphamide and colchicine
      tested in the in vitro mammalian cell micronucleus test (MNvit) in the presence
      and absence of cytokinesis block using L5178Y mouse lymphoma cells and 2
      aminoanthracene tested in MNvit in the absence of cytokinesis block using TK6
      cells at AstraZeneca UK, in support of OECD draft Test Guideline 487.
AB  - At the laboratories of AstraZeneca, Alderley Park, UK the reference genotoxic
      agents etoposide (a topoisomerase II inhibitor), cadmium chloride (an inorganic
      carcinogen), colchicine (an aneugen that inhibits tubulin polymerisation),
      benzo[a]pyrene (a metabolism dependent reference genotoxin) and cyclophosphamide
      (a metabolism dependent reference genotoxin) were tested in the in vitro
      micronucleus assay (MNvit), using mouse lymphoma L5178Y cells, with and without
      cytokinesis block. Further, 2-aminoanthracene (a metabolism dependent weak
      clastogen) was tested in the MNvit, using TK6 cells, without cytokinesis block.
      This was done in support of the toxicity (cell death and cytostasis) measures
      recommended in the late 2007 version of the draft OECD Test Guideline 487 for the
      testing of chemicals. All six reference agents were positive in the MNvit without
      cytokinesis block at concentrations giving approximately 50% toxicity or less as
      defined by draft Test Guideline 487 recommended measures, relative population
      doublings and relative increase in cell counts. Furthermore, the five agents
      tested with cytokinesis block were positive in the MNvit at concentrations giving
      approximately 50% toxicity or less as assessed by replicative index. Accordingly,
      this work supports the premise that relative population doublings and relative
      increase in cell counts are appropriate measures of toxicity for the non
      cytokinesis-blocked in vitro micronucleus assay.

PMID- 19761868
TI  - Inhibition of carboxylesterase activity of THP1 monocytes/macrophages and
      recombinant human carboxylesterase 1 by oxysterols and fatty acids.
AB  - Two major isoforms of human carboxylesterases (CEs) are found in metabolically
      active tissues, CES1 and CES2. These hydrolytic enzymes are involved in
      xenobiotic and endobiotic metabolism. CES1 is abundantly expressed in human liver
      and monocytes/macrophages, including the THP1 cell line; CES2 is expressed in
      liver but not in monocytes/macrophages. The cholesteryl ester hydrolysis activity
      in human macrophages has been attributed to CES1. Here, we report the direct
      inhibitory effects of several endogenous oxysterols and fatty acids on the CE
      activity of THP1 monocytes/macrophages and recombinant human CES1 and CES2. Using
      THP1 whole-cell lysates we found: (1) 27-hydroxycholesterol (27-HC) is a potent
      inhibitor of carboxylesterase activity (IC50=33 nM); (2) 24(S),25
      epoxycholesterol had moderate inhibitory activity (IC(50)=8.1 microM); and (3)
      cholesterol, 7-ketocholesterol, 22(R)-hydroxycholesterol, 24(S)
      hydroxycholesterol, and 25-hydroxycholesterol each had little inhibitory
      activity. 27-HC was a partially noncompetitive inhibitor of recombinant CES1
      (K(iapp)=10 nM) and impaired intracellular CES1 activity following treatment of
      intact THP1 cells. In contrast, recombinant CES2 activity was not inhibited by 27
      HC, suggesting isoform-selective inhibition by 27-HC. Furthermore, unsaturated
      fatty acids were better inhibitors of CES1 activity than saturated fatty acids,
      while CES2 activity was unaffected by any fatty acid. Arachidonic acid (AA) was
      the most potent fatty acid inhibitor of recombinant CES1 and acted by a
      noncompetitive mechanism (K(iapp)=1.7 microM); when not complexed to albumin,
      exogenous AA penetrated intact THP1 cells and inhibited CES1. Inhibition results
      are discussed in light of recent structural models for CES1 that describe ligand
      binding sites separate from the active site. In addition, oxysterol-mediated
      inhibition of CES1 activity was demonstrated by pretreatment of human liver
      homogenates or intact THP1 cells with exogenous 27-HC, which resulted in
      significantly reduced hydrolysis of the pyrethroid insecticide bioresmethrin, a
      CES1-specific xenobiotic substrate. Collectively, these findings suggest that CE
      activity of recombinant CES1, cell lysates, and intact cells can be impaired by
      naturally occurring lipids, which may compromise the ability of CES1 to both
      detoxify environmental pollutants and metabolize endogenous compounds in vivo.

PMID- 19761869
TI  - Apolipoprotein C-I reduces cholesteryl esters selective uptake from LDL and HDL
      by binding to HepG2 cells and lipoproteins.
AB  - Plasma cholesterol from low- and high-density lipoproteins (LDL and HDL) are
      cleared from the circulation by specific receptors that either totally degrade
      lipoproteins as the LDL receptor or selectively take up their cholesteryl esters
      (CE) like the scavenger receptor class B type I (SR-BI). The aim of the present
      study was to define the effect of apoC-I on the uptake of LDL and HDL(3) by HepG2
      cells. In experiments conducted with exogenously added purified apoC-I, no
      significant effect was observed on lipoprotein-protein association and
      degradation; however, LDL- and HDL(3)-CE selective uptake was significantly
      reduced in a dose-dependent manner. This study also shows that apoC-I has the
      ability to associate with HepG2 cells and with LDL and HDL(3). Moreover, pre
      incubation of HepG2 cells with apoC-I reduces HDL(3)-CE selective uptake and pre
      incubation of LDL and HDL(3) with apoC-I decreases their CE selective uptake by
      HepG2 cells. Thus, apoC-I can accomplish its inhibitory effect on SR-BI activity
      by either binding to SR-BI or lipoproteins. We conclude that by reducing hepatic
      lipoprotein-CE selective uptake, apoC-I has an atherogenic character.

PMID- 19761870
TI  - Reflective Random Indexing and indirect inference: a scalable method for
      discovery of implicit connections.
AB  - The discovery of implicit connections between terms that do not occur together in
      any scientific document underlies the model of literature-based knowledge
      discovery first proposed by Swanson. Corpus-derived statistical models of
      semantic distance such as Latent Semantic Analysis (LSA) have been evaluated
      previously as methods for the discovery of such implicit connections. However,
      LSA in particular is dependent on a computationally demanding method of dimension
      reduction as a means to obtain meaningful indirect inference, limiting its
      ability to scale to large text corpora. In this paper, we evaluate the ability of
      Random Indexing (RI), a scalable distributional model of word associations, to
      draw meaningful implicit relationships between terms in general and biomedical
      language. Proponents of this method have achieved comparable performance to LSA
      on several cognitive tasks while using a simpler and less computationally
      demanding method of dimension reduction than LSA employs. In this paper, we
      demonstrate that the original implementation of RI is ineffective at inferring
      meaningful indirect connections, and evaluate Reflective Random Indexing (RRI),
      an iterative variant of the method that is better able to perform indirect
      inference. RRI is shown to lead to more clearly related indirect connections and
      to outperform existing RI implementations in the prediction of future direct co
      occurrence in the MEDLINE corpus.

PMID- 19761872
TI  - Kidney specific expression of cTPTE during development of the chick embryo.
AB  - Here we report the cloning and expression of chick TPTE, the avian ortholog of
      the mammalian pTEN2 gene. In the chick embryo, cTPTE expression begins at HH
      (Hamburger and Hamilton) stage 18 and is restricted to the tubular structures of
      the developing kidney. In the mesonephros, cTPTE expression localizes to the
      proximal tubules. In the adult kidney cTPTE expression is no longer detectable.
      The data presented here suggest that cTPTE plays an important role in the
      regulation of embryonic kidney function.

PMID- 19761873
TI  - Intratracheal instillation of bone marrow-derived cell in an experimental model
      of silicosis.
AB  - The time course of lung mechanics, histology, and inflammatory and fibrogenic
      mediators are analysed after intratracheal instillation (IT) of bone marrow
      derived cells (BMDC) in a model of silicosis. C57BL/6 mice were randomly divided
      into SIL (silica, 20mg IT) and control (CTRL) groups (saline IT). At day 15, mice
      received saline or BMDC (2 x 10(6)cells) IT. The biodistribution of technetium
      99m BMDC was higher in lungs compared with other organs. At days 30 and 60, lung
      mechanics, the area of granulomatous nodules, and mRNA expression of IL-1beta and
      TGF-beta were higher in SIL than CTRL animals. BMDC minimized changes in lung
      mechanics, the area of granulomatous nodules, and total cell infiltration at day
      30, but these effects were no longer observed at day 60. Conversely, BMDC avoided
      the expression of IL-1beta at days 30 and 60 and TGF-beta only at day 30. In
      conclusion, BMDC therapy improved lung mechanics and histology, but this
      beneficial effect was not maintained in the course of injury.

PMID- 19761874
TI  - Effects of different respiratory muscle training regimes on fatigue-related
      variables during volitional hyperpnoea.
AB  - We compared the effects of the most commonly used respiratory muscle (RM)
      training regimes: RM endurance training (RMET; normocapnic hyperpnoea) and
      inspiratory resistive training (IMT), on RM performance. Twenty-six healthy men
      were randomized into 3 groups performing 4 weeks of RMET, IMT or sham-training.
      Lung function, RM strength and endurance were tested before and after training.
      RM fatigue during intermittent hyperpnoea was assessed by twitch oesophageal
      (P(oes,tw)) and gastric pressures with cervical and thoracic magnetic
      stimulation. Respiratory sensations (visual analogue scale, 0-10) and blood
      lactate concentrations ([La]) were assessed during hyperpnoea. RMET increased
      maximal voluntary ventilation while IMT increased maximal inspiratory pressure.
      Both RMET and IMT increased vital capacity and RM endurance, but only RMET
      improved the development of inspiratory muscle fatigue (from -31% to -21%
      P(oes,tw)), perception of respiratory exertion (4.2+/-0.1 to 2.3+/-2.3 points)
      and [La] (1.8+/-0.4 to 1.3+/-0.3 mmol l(-1)) during hyperpnoea. Whether these
      specific RMET-induced adaptations observed during hyperpnoea would translate into
      greater improvements in exercise performance compared to IMT remains to be
      investigated.

PMID- 19761871
TI  - Treatment of nonalcoholic fatty liver disease in children: TONIC trial design.
AB  - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) in children can lead to
      steatohepatitis, cirrhosis, and end-stage liver disease. The cause of NAFLD is
      unknown, but it is commonly associated with obesity, insulin resistance, and
      dyslipidemia. OBJECTIVES: TONIC is conducted to test whether treatment with
      metformin, an insulin sensitizer, or vitamin E, a naturally available
      antioxidant, will lead to improvements in biochemical and histological features
      of nondiabetic children with biopsy-proven NAFLD. DESIGN: TONIC is a randomized,
      multicenter, double-masked, placebo-controlled trial of 96 weeks of treatment
      with metformin or vitamin E. The primary outcome measure chosen for the trial is
      improvement in serum alanine aminotransferase (ALT) levels with treatment as
      compared to placebo. An improvement in ALT is defined as reduction in serum ALT
      levels to below 50% of the baseline values or into the normal range (40 U/L or
      less) during the last 48 weeks of treatment. Histological improvement is defined
      by changes in liver histology between a baseline and end-of-treatment liver
      biopsy in regards to (1) steatohepatitis, (2) NAFLD Activity Score, consisting of
      scores for steatosis, lobular inflammation, and hepatocellular injury
      (ballooning), and (3) fibrosis score. METHODS: Between September 2005 and
      September 2007, 173 children were enrolled into TONIC at 10 clinical centers in
      the United States. Participants were randomized to receive either metformin (500
      mg b.i.d.), vitamin E (400 IU b.i.d.), or placebo for 96 weeks. This protocol was
      approved by all participating center Institutional Review Boards (IRBs) and an
      independent Data and Safety Monitoring Board (DSMB). (ClinicalTrials.gov number,
      NCT00063635.).

PMID- 19761875
TI  - Structure-function analysis of VEGF receptor activation and the role of
      coreceptors in angiogenic signaling.
AB  - Vascular endothelial growth factors (VEGFs) constitute a family of six
      polypeptides, VEGF-A, -B, -C, -D, -E and PlGF, that regulate blood and lymphatic
      vessel development. VEGFs specifically bind to three type V receptor tyrosine
      kinases (RTKs), VEGFR-1, -2 and -3, and to coreceptors such as neuropilins and
      heparan sulfate proteoglycans (HSPG). VEGFRs are activated upon ligand-induced
      dimerization mediated by the extracellular domain (ECD). A study using receptor
      constructs carrying artificial dimerization-promoting transmembrane domains
      (TMDs) showed that receptor dimerization is necessary, but not sufficient, for
      receptor activation and demonstrates that distinct orientation of receptor
      monomers is required to instigate transmembrane signaling. Angiogenic signaling
      by VEGF receptors also depends on cooperation with specific coreceptors such as
      neuropilins and HSPG. A number of VEGF isoforms differ in binding to coreceptors,
      and ligand-specific signal output is apparently the result of the specific
      coreceptor complex assembled by a particular VEGF isoform. Here we discuss the
      structural features of VEGF family ligands and their receptors in relation to
      their distinct signal output and angiogenic potential.

PMID- 19761876
TI  - A novel potentiometric method for the determination of real crosslinking ratio of
      poly(aspartic acid) gels.
AB  - In order to obtain nontoxic functional polymer gels for biomedical applications,
      chemically crosslinked poly(aspartic acid) gels have been prepared using 1,4
      diaminobutane as crosslinker. The presence of COOH and amino groups on the
      network chains renders these gels pH sensitive. Due to the specific hydrophobic
      hydrophilic balance, these gels show a significant volume transition at a well
      defined pH close to the pK value of uncrosslinked poly(aspartic acid). Since the
      magnitude of volume change critically depends on the degree of crosslinking, it
      is an important task to determine the topological characteristics of these
      networks. A novel method based on potentiometric acid-base titration has been
      developed to assess the crosslinking ratio, excluding physical crosslinks and
      entanglements. It turned out that only 25% of all crosslinker molecules forms
      real crosslinks between the poly(aspartic acid) chains; the rest react with one
      of its functional groups and forms short pendant side chains. At a nominal
      crosslinking ratio of 0.1, the number average molecular mass between crosslinks
      is found to be M(c) = 2300.

PMID- 19761877
TI  - Yeast cultures with UCP1 uncoupling activity as a heating device.
AB  - Uncoupling proteins (UCPs) are mitochondrial transporters that facilitate
      controlled dissipation of the proton gradient and thus regulate energetic
      efficiency. The heat generating capacity of UCP from brown adipose tissue was
      investigated in yeasts expressing the protein recombinantly under conditions in
      which the temperature of the growth medium was measured directly. A Liquid
      Culture Calorimeter (LCC) was built consisting of a thermally isolated culture
      flask able to keep yeast cultures warm without resorting to additional heating.
      The exact internal temperature of the cultures was monitored for 24h through a
      thermocouple connected to a data logger. Under these conditions, significant
      temperature increases (1 degrees C) in the media were recorded when yeast strains
      expressing endogenously active UCP1 mutants were grown. This is the first direct
      evidence, in a eukaryotic microbial model, of a temperature rise associated with
      uncoupling activity, and could be seen as the first step toward developing a
      biological heating device.

PMID- 19761878
TI  - A microsatellite (SSR) based linkage map of Brassica rapa.
AB  - In the present study we describe the construction of a genetic linkage map for
      the Brassica rapa (AA) genome that will act as a key resource in undertaking
      future structural and functional genomic studies in B. rapa. A F(2) mapping
      population consisting of 48 F(2) individual plants developed following
      hybridization of 2 inbred lines Bathari mandi and IC 331817 was used to construct
      the map. The map comprises 53 SSR markers derived from 3 different public domain
      resources. Nine linkage groups along with a small subgroup were identified and
      designated as R(1)-R(9) through alignment and orientation using SSR markers in
      common with existing B. rapa reference linkage maps. The total length of the
      genetic linkage map was 354.6 cm with an average interval of 6.6 cm between
      adjacent loci. The length of linkage groups ranged from 28.0 cm to 44.2 cm for
      R(6) and R(1A), respectively. The number variability of markers in the 9 linkage
      groups ranged from 3 for R(6) to 10 for R(1). Of the 53 SSR markers assigned to
      the linkage groups, only 5 (9.4%) showed deviation from the expected segregation
      ratio. The development of this map is vital to the genome integration and genetic
      information and will enable the international research community to share
      resources and data for the improvement of B. rapa and other cultivated Brassica
      species.

PMID- 19761879
TI  - Production of high level of cellulase-poor xylanases by wild strains of white-rot
      fungus Coprinellus disseminatus in solid-state fermentation.
AB  - The production, optimisation and partial characterisation of xylanases from newly
      isolated wild strains of Coprinellus disseminatus was performed in solid-state
      fermentation. Strains SH-1 and SH-2 showed high xylanase (727.78 and 227.99
      IU/mL) with very low CMCase (0.925 and 0.660 IU/mL) and laccase (0.640 and 0.742
      U/mL) activities at incubation time seven days, 37 degrees C and initial pH 6.4,
      using yeast extract as nitrogen source and cheap substrate (wheat bran), which
      increased the cost effectiveness of the process. Crude cellulase-poor xylanases
      obtained from test strains showed maximum activities at 55 degrees C and pH 6.4
      and retained 32.64 (SH-1) and 35.03% (SH-2) activity at pH 8 and 43.01 (SH-1) and
      25.00% (SH-2) activity at 65 degrees C. As test strains produced high level of
      cellulase-poor xylanases, which were active over a wide range of temperature and
      pH, these enzymes might be used as pulp biobleaching agents.

PMID- 19761880
TI  - Bone sialoprotein, but not osteopontin, deficiency impairs the mineralization of
      regenerating bone during cortical defect healing.
AB  - Bone healing is a complex multi-step process, which depends on the position and
      size of the lesion, and on the mechanical stability of the wounded area. To
      address more specifically the mechanisms involved in cortical bone healing, we
      created drill-hole defects in the cortex of mouse femur, a lesion that triggers
      intramembranous repair, and compared the roles of bone sialoprotein (BSP) and
      osteopontin (OPN), two proteins of the extracellular matrix, in the repair
      process. Bone regeneration was analyzed by ex vivo microcomputerized X-ray
      tomography and histomorphometry of bones of BSP-deficient, OPN-deficient and wild
      type mice. In all mouse strains, the cortical gap was bridged with woven bone
      within 2 weeks and no mineralized tissue was observed in the marrow. Within 3
      weeks, lamellar cortical bone filled the gap. The amount and degree of
      mineralization of the woven bone was not affected by OPN deficiency, but cortical
      bone healing was delayed in BSP-deficient mice due to delayed mineralization.
      Gene expression studies showed a higher amount of BSP transcripts in the repair
      bone of OPN-deficient mice, suggesting a possible compensation of OPN function by
      BSP in OPN-null mice. Our data suggest that BSP, but not OPN, plays a role in
      primary bone formation and mineralization of newly formed bone during the process
      of cortical bone healing.

PMID- 19761881
TI  - Systematic evaluation of a tissue-engineered bone for maxillary sinus
      augmentation in large animal canine model.
AB  - The objective of this study is to systematically evaluate the effects of a tissue
      engineered bone complex for maxillary sinus augmentation in a canine model.
      Twelve sinus floor augmentation surgeries in 6 animals were performed bilaterally
      and randomly repaired with the following 3 groups of grafts: group A consisted of
      tissue-engineered osteoblasts/beta-TCP complex (n=4); group B consisted of beta
      TCP alone (n=4); group C consisted of autogenous bone obtained from iliac crest
      as a positive control (n=4). All dogs had uneventful healings following the
      surgery. Sequential polychrome fluorescent labeling, maxillofacial CT,
      microhardness tests, as well as histological and histomorphometric analyses
      indicated that the tissue-engineered osteoblasts/beta-TCP complex dramatically
      promoted bone formation and mineralization and maximally maintained the height
      and volume of elevated maxillary sinus. By comparison, both control groups of
      beta-TCP or autologous iliac bone showed considerable resorption and replacement
      by fibrous or fatty tissue. We thus conclude that beta-TCP alone could barely
      maintain the height and volume of the elevated sinus floor, and that the
      transplantation of autogenous osteoblasts on beta-TCP could promote earlier bone
      formation and mineralization, maximally maintain height, volume and increase the
      compressive strength of augmented maxillary sinus. This tissue engineered bone
      complex might be a better alternative to autologous bone for the clinical
      edentulous maxillary sinus augmentation.

PMID- 19761882
TI  - Lack of sexual dimorphism in femora of the eusocial and hypogonadic naked mole
      rat: a novel animal model for the study of delayed puberty on the skeletal
      system.
AB  - Sex steroid hormones are major determinants of bone morphology and quality and
      are responsible for sexually dimorphic skeletal traits. Hypogonadism results in
      suboptimal skeletal development and may lead to an increased risk of bone
      fracture later in life. The etiology of delayed puberty and/or hypothalamic
      amenorrhea is poorly understood, and experimental animal models addressing this
      issue are predominantly based upon short-term experimental induction of hormonal
      suppression via gonadotropin releasing hormone antagonists (GnRH-a). This acute
      change in hormone profile does not necessarily emulate the natural progression of
      hypogonadic bone disorders. We propose a novel animal model with which to explore
      the effects of chronic hypogonadism on bone quality, the naked mole-rat (NMR;
      Heterocephalus glaber). This mouse-size rodent may remain reproductively
      suppressed throughout its life, if it remains as a subordinate within the
      eusocial mole-rat colony. NMRs live in large colonies with a single dominant
      breeding female. She, primarily by using aggressive social contact, naturally
      suppresses the hypothalamic gonadotropic axis of subordinate NMRs and thereby
      their reproductive expression. However, should an NMR be separated from the
      dominant breeder, within less than a week reproductive hormones may become
      elevated and the animal attains breeding status. We questioned if sexual
      suppression of subordinates impact upon the development and maintenance of the
      femora and lead to a sexually indistinct monomorphic skeleton. Femora were
      obtained from male and female NMRs that were either non-breeders (subordinate) or
      breeders at the time of sacrifice. Diaphyseal cross-sectional morphology,
      metaphyseal trabecular micro-architecture and tissue mineral density of the femur
      were measured using microcomputed tomography and diaphyseal mechanical properties
      were assessed by four-point bending tests to failure. Subordinates were sexually
      monomorphic and showed no significant differences in body weight or femoral bone
      structure and quality between males and females. Femora of subordinate females
      differed significantly from that of breeding animals, whereas in males, the
      divergent trend among breeders and non-breeders did not reach statistical
      significance. Subordinate NMRs, naturally suppressed from entering puberty, may
      prove to be a useful model to tease apart the relationship between bone
      morphology and hypogonadism and evaluate skeletal development during pubertal
      maturation.

PMID- 19761883
TI  - Partial rescue of postnatal growth plate abnormalities in Ihh mutants by
      expression of a constitutively active PTH/PTHrP receptor.
AB  - Indian hedgehog (Ihh) is essential for chondrocyte proliferation/differentiation
      and osteoblast differentiation during prenatal endochondral bone formation. Ihh
      expression in postnatal chondrocytes has a non-redundant role in maintaining a
      growth plate and sustaining trabecular bone after birth. Loss of Ihh in postnatal
      chondrocytes results in fusion of the growth plate and a decrease in trabecular
      bone. In order to normalize this abnormal chondrocyte phenotype and to
      investigate whether a putative rescue of the growth plate anomalies is sufficient
      to correct the severe alterations in the bone, we expressed a constitutively
      active PTH/PTHrP receptor (an Ihh downstream target) in the chondrocytes of Col2
      alpha 1-Cre ER; Ihh(dld) mice by mating Col2 alpha 1-Cre ER; Ihh(fl/fl) mice with
      Col2 alpha 1-constitutively active PTH/PTHrP receptor transgenic mice (Jansen,
      J). Col2 alpha 1-Cre ER; Ihh(f/f); J mice were then injected with tamoxifen at P0
      to generate Col2 alpha 1-Cre ER; Ihh(d/d); J mice. In contrast with the
      previously reported growth plate phenotype of Col2 alpha 1-Cre ER; Ihh(d/d) mice
      that displayed ectopic chondrocyte hypertrophy at P7, growth plates of Col2 alpha
      1-Cre ER; Ihh(d/d); J double mutants were well organized, and exhibited a gene
      expression pattern similar to the one of control mice. However, expression of
      osteoblast markers and Dkk1, a Wnt signaling target, remains decreased in the
      bone collar of Col2 alpha 1-Cre ER; Ihh(d/d); J mice when compared to control
      mice despite the rescue of abnormal chondrocyte differentiation. Moreover,
      proliferation of chondrocytes was still significantly impaired in Col2 alpha 1
      Cre ER; Ihh(d/d); J mice, and this eventually led to the fusion of the growth
      plate at P14. In summary, we have demonstrated that expression of a Jansen
      receptor in chondrocytes was able to rescue abnormal chondrocyte differentiation
      but not impaired chondrocyte proliferation and the bone anomalies in mice lacking
      the Ihh gene in chondrocytes after birth. Taken together, our findings suggest
      that Ihh has both PTHrP-dependent and -independent functions during postnatal
      endochondral bone development.

PMID- 19761884
TI  - Quantitative MR T2 measurement of articular cartilage to assess the treatment
      effect of intra-articular hyaluronic acid injection on experimental
      osteoarthritis induced by ACLX.
AB  - OBJECTIVE: The purpose of this study was to investigate whether the effect of
      treatment with hyaluronic acid (HA) on cartilage in osteoarthritis (OA) can be
      determined by measuring the magnetic resonance (MR) T2 value of cartilage in an
      anterior cruciate ligament transection (ACLX) animal model. METHOD: Eighteen male
      Sprague Dawley rats were separated randomly into three groups (n=6 for each
      group). Group 1 was given ACLX and intra-articular (IA) normal saline (NS)
      injection (ACLX+NS), group 2 was given ACLX and IA HA injection (ACLX+HA), and
      group 3 was the sham control. The ACLX+NS and ACLX+HA groups received ACLX on the
      right knee at 8 weeks of age and were then treated with IA NS or HA injection
      once a week, respectively, for 4 weeks starting at 13 weeks of age. In the sham
      control group, the right knee joint was opened surgically but ACLX was not
      performed at 8 weeks of age. MR T2 measurements were obtained on all rats at 8,
      12, and 21 weeks of age, and histological Mankin scoring was performed at 21
      weeks of age. RESULTS: Five weeks after the 4-week treatment, the MR T2 value of
      the ACLX right knee cartilage was significantly lower in ACLX+HA (29.58+/-1.12ms)
      than in ACLX+NS (32.04+/-1.39ms) (P<0.05). Five weeks after the 4-week treatment,
      the Mankin score of the ACLX right knee was significantly lower in ACLX+HA (3.3+/
      0.81) than in ACLX+NS (7.3+/-1.03) (P<0.001). The T2 value was significantly and
      positively correlated with the Mankin score in the ACLX+NS (rho=0.77, P<0.05) and
      ACLX+HA (rho=0.69, P<0.05) groups. CONCLUSION: This study demonstrates the
      feasibility of quantitative MR T2 measurement in the early assessment of HA
      treatment efficiency in a cartilage degeneration model.

PMID- 19761885
TI  - [Guidelines for the diagnosis and treatment of cutaneous squamous cell carcinoma
      and precursor lesions].

PMID- 19761886
TI  - Low serum 25-hydroxyvitamin D concentrations are associated with greater all
      cause mortality in older community-dwelling women.
AB  - Vitamin D deficiency is associated with osteoporosis, poor muscle strength,
      falls, and fractures. The relationship between serum vitamin D concentrations and
      mortality in older community-dwelling women has not been well characterized. We
      hypothesized that women with lower 25-hydroxyvitamin D (25[OH]D) concentrations
      were at higher risk of mortality. We examined the association between serum
      25[OH]D concentrations and all-cause mortality in a prospective, population-based
      study of 714 community-dwelling women, aged 70 to 79 years, the Women's Health
      and Aging Studies I and II in Baltimore, Md. The studies were originally designed
      to evaluate the causes and course of physical disability in older women living in
      the community. Vital status was determined through follow-up interviews and
      matching with the National Death Index. During a median of 72 months of follow
      up, 100 (14%) of 714 women died. Women in the lowest quartile of 25(OH)D (<15.3
      ng/mL or 38.2 nmol/L) were at higher risk of death (hazards ratio, 2.45; 95%
      confidence interval, 1.12-5.36; P = .02) compared to women in the highest
      quartile (>27.0 ng/mL or 67.4 nmol/L) of 25(OH)D in a multivariate Cox
      proportional hazards model adjusting for demographics, season, and conventional
      risk factors. Older community-dwelling women with low 25(OH)D levels are at an
      increased risk of death.

PMID- 19761887
TI  - Validation of the BIOPAC indirect calorimeter for determining resting energy
      expenditure in healthy free-living older people.
AB  - The BIOPAC indirect calorimeter for measuring resting energy expenditure (REE) is
      less cumbersome than many other calorimeters. We tested the hypothesis that the
      BIOPAC calorimeter is as well suited for determining REE in older people as
      traditional calorimeters. In 50 healthy persons (24 men and 26 women; age range,
      61-83 years), REE by BIOPAC was validated against Vmax Spectra indirect
      calorimeter as a criterion method. Resting energy expenditure by BIOPAC was
      recorded at 2 different time intervals to find optimal conditions for older
      persons. Also, REE by 7 published equations was validated. The Bland-Altman
      procedure was used to test agreement between methods. Multiple regression
      analysis was applied to develop a new equation for predicting REE from BIOPAC.
      The BIOPAC calorimeter and most empirical equations significantly overpredicted
      mean REE in both sexes. Mifflin's equation best-predicted mean REE. Limits of
      agreement were wide for BIOPAC and narrow for most empirical equations. The
      Luhrmann and Muller equations had smallest limits of agreement in men (+/-950
      kJ/24 h) and the Harris-Benedict and Muller equations in women (+/-672 kJ/24 h).
      A new equation was developed for the BIOPAC device improving both predictions of
      mean and individual REE (R(2) = 0.671, standard error of the estimate = 136 kJ/24
      h). Using this equation, 72.9% of subjects were lying within 10% of measured REE,
      compared with only 12.5% when using the manufacturer's algorithm. In conclusion,
      the BIOPAC calorimeter is suitable for measuring REE in healthy older adults when
      the new prediction equation is applied. This calorimeter is not applicable to
      frail older persons.

PMID- 19761888
TI  - A 12-week worksite health promotion program reduces cardiovascular risk factors
      in male workers with the apolipoprotein E2 and apolipoprotein E3 genotypes, but
      not in apolipoprotein E4 genotype.
AB  - Worksite health promotion programs focusing on diet and lifestyle modification
      have been shown to improve health outcomes in workers. The purpose of this study
      was to investigate whether a 12-week worksite health promotion program shows
      different response of cardiovascular risk factors in subjects according to
      apolipoprotein E (Apo E) genotype and obesity level in 141 male Korean industrial
      workers. We hypothesized that the health changes of a 12-week intervention may
      not be the same within Apo E genotypes in nonobese and obese subjects. They
      received 5 face-to-face meetings based on their health profiles. In obese group
      carrying Apo E3 genotype, body mass index, body fat (%), waist circumference,
      waist-hip ratio, and systolic blood pressure were decreased, as well as intakes
      of energy (P = .000) and carbohydrate (P = .005). High-density lipoprotein
      cholesterol (P = .004) level was improved in individuals with the Apo E2
      genotype. These beneficial effects were only observed in individuals with the Apo
      E2 or Apo E3 genotype. Multiple linear regression revealed that obesity was
      strongly correlated with waist circumference (P = .002), plasma total cholesterol
      (P = .037), and changes in dietary cholesterol intake (P = .011) in individuals
      with the Apo E3 genotype, whereas only changes in dietary fat intake (P = .044)
      was correlated in those with the Apo E4 genotype. Overall, the results of this
      study suggest that a health promotion program can be a useful method of improving
      cardiovascular risk factors and dietary intake in industrial workers with certain
      genotypes only. Therefore, further research is needed to develop a tailored, long
      term worksite health promotion program based on genetic background.

PMID- 19761889
TI  - Glycemic response of mashed potato containing high-viscocity
      hydroxypropylmethylcellulose.
AB  - Potatoes generally have one of the highest glycemic index values of any food.
      Relatively small differences in the glycemic response (GR) of regularly consumed
      starch foods have shown beneficial effects on health. Lowering the GR of a potato
      based meal has potentially wide-reaching health benefits. High-viscosity
      hydroxypropylmethylcellulose (HV-HPMC) is a modified cellulose dietary fiber
      extensively used in the food industry. We hypothesized that the GR of a high
      glycemic index product such as mashed potato would be lower with the addition of
      HV-HPMC. In a nonblind, randomized, repeat-measure, crossover controlled trial,
      15 healthy adults consumed portions of mashed potato with different doses (0%,
      1%, 2%, and 4%) of a specially selected and optimized HV-HPMC and a reference
      food (glucose) on separate occasions. Five subjects were excluded from the final
      analysis due to noncompliance with study procedures. Capillary blood glucose was
      measured in fasted subjects and at 15, 30, 45, 60, 90, and 120 minutes after
      starting to eat. For each sample, the incremental area under the blood glucose
      response curve was calculated and the GR determined. There was a significant
      lowering effect of HV-HPMC on GR (P < .001) of mashed potato. Glycemic responses
      for all mashed potato samples with the HV-HPMC were significantly lower than the
      standard mashed potato: 1% level (P < .05), 2% level (P < .05), and 4% level (P <
      .05). However, there was no significant effect of the HV-HPMC dose on GR. We
      conclude that addition of select HV-HPMC to mashed potato blunts GR.

PMID- 19761890
TI  - Prolonged in vitro exposure to white wines enhances the erosive damage on human
      permanent teeth compared with red wines.
AB  - The aim of this in vitro study was to determine and compare the erosive
      potentials of red and white wines, exerted on enamel surfaces prepared from
      extracted human permanent teeth. European wines (50 red, 50 white wines) from
      different regions were purchased, and the pH values were measured. Eight wines
      with different pH values were selected. Enamel samples with an average surface
      area of 25 mm(2) were prepared from 25 extracted permanent teeth from male and
      female patients aged 40 to 65 years and incubated with wines for up to 24 hours;
      the amounts of released calcium were determined colorimetrically, and mean
      surface roughness was measured with a profilometer. A quantitative elemental
      analysis for Ca was carried out in various depths (5-50 microm), using an
      electron probe microanalyzer. Incubation of the enamel surfaces with different
      wines caused a time-dependent release of calcium. After 24 hours, white wines
      caused a significantly higher (P = .003) Ca release (range: 8.74-28.56 mg dL(-1)
      25 mm(-2)) than red wines (range: 4.85-19.43 mg dL(-1) 25 mm(-2)), whereas the
      values for surface roughness were similar (white wines: 2.67 +/- 0.92 microm; red
      wines: 2.64 +/- 0.66 mum). Incubation with white wines resulted in a higher loss
      of Ca down to a depth of 60 microm. In this study, it was demonstrated that white
      wines have higher erosive potentials than red wines. Within the limits of this in
      vitro study, it can be predicted that a frequent consumption of white wines might
      lead to severe dental erosion.

PMID- 19761891
TI  - Select phytochemicals suppress human T-lymphocytes and mouse splenocytes
      suggesting their use in autoimmunity and transplantation.
AB  - We have considered a novel "rational" gene targeting approach for treating
      pathologies whose genetic bases are defined using select phytochemicals. We
      reason that one such potential application of this approach would be conditions
      requiring immunosuppression such as autoimmune disease and transplantation, where
      the genetic target is clearly defined; i.e., interleukin-2 and associated T-cell
      activation. Therefore, we hypothesized that select phytochemicals can suppress T
      lymphocyte proliferation both in vitro and in vivo. The immunosuppressive effects
      of berry extract, curcumin, quercetin, sulforaphane, epigallocatechin gallate
      (EGCG), resveratrol, alpha-tocopherol, vitamin C and sucrose were tested on anti
      CD3 plus anti-CD28-activated primary human T-lymphocytes in culture. Curcumin,
      sulforaphane, quercetin, berry extract and EGCG all significantly inhibited T
      cell proliferation, and this effect was not due to toxicity. IL-2 production was
      also reduced by these agents, implicating this important T-cell cytokine in
      proliferation suppression. Except for berry extract, these same agents also
      inhibited mouse splenic T-cell proliferation and IL-2 production. Subsequent in
      vivo studies revealed that quercetin (but not sulforaphane) modestly suppressed
      mouse splenocyte proliferation following supplementation of BALB/c mice diets.
      This effect was especially prominent if corrected for the loss of supplement
      "recall" as observed in cultured T-cells. These results suggest the potential use
      of these select phytochemicals for treating autoimmune and transplant patients,
      and support our strategy of using select phytochemicals to treat genetically
      defined pathologies, an approach that we believe is simple, healthy, and cost
      effective.

PMID- 19761892
TI  - Aqueous extract of Abutilon indicum Sweet inhibits glucose absorption and
      stimulates insulin secretion in rodents.
AB  - The objective of this study was to evaluate the antidiabetic effects of the
      aqueous extract derived from the Thai Abutilon indicum Sweet plant and to explore
      its effects on intestinal glucose absorption and insulin secretion. The authors
      hypothesized that the plasma glucose level could be reduced through the
      inhibition of glucose absorption and/or the enhancement of insulin secretion.
      Administration of the extract (0.5 and 1 g/kg body weight) in an oral glucose
      tolerance test led to a significant reduction in plasma glucose levels in 30
      minutes after the administration in moderately diabetic rats, as compared with
      untreated rats (P < .05), and this was at a faster rate than the use of an
      antidiabetic drug, glibenclamide. The inhibition of glucose absorption through
      the small intestine was investigated using an everted intestinal sac. The results
      showed that the extract at concentrations of 0.156 to 5 mg/mL caused a reduction
      of glucose absorption in a dose response manner. The maximum response was noted
      at a dose of 2.5 mg/mL. The promotion of the extract on insulin secretion was
      confirmed by incubating beta cell of pancreatic islets and INS-1E insulinoma
      cells with the extract at 1 to 1000 microg/mL. These observations suggest that
      the aqueous extract from the A indicum plant has antidiabetic properties, which
      inhibited glucose absorption and stimulated insulin secretion. Phytochemical
      screening also revealed that the extract contained alkaloids, flavonoids,
      tannins, glycosides, and saponins that could account for the observed
      pharmacologic effects of the plant extract.

PMID- 19761893
TI  - Bioefficacy of beta-carotene is improved in rats after solubilized as equimolar
      dose of beta-carotene and lutein in phospholipid-mixed micelles.
AB  - beta-Carotene (BC) is a potent dietary source of vitamin A for populations at
      risk of vitamin A deficiency, yet its bioavailability is influenced by several
      factors such as dietary fat, carotenoids type, and other components. We
      hypothesize that type of micellar phospholipids influence bioefficacy of
      carotenoids and activity of carotenoid metabolizing enzymes. This study
      determined the BC bioefficacy in rats (n = 5/time point) after an equimolar dose
      of BC and lutein (Lut) solubilized in micelles containing either
      phosphatidylcholine (PC) or lysophosphatidylcholine (LPC), or no phospholipid
      (NoPL). Results show that no BC and Lut was detected in the plasma of rats at 0
      hour, but after gavage, the mean (SD) area under the curve (AUC; in picomoles per
      milliliter) of plasma BC for 6 hours in PC, LPC, and NoPL groups were 1145 (132),
      965 (199), and 2136 (112), respectively. The AUC value of plasma Lut in LPC group
      (183 +/- 23 pmol mL(-1) h(-1)) was higher than the other 2 groups. Similarly,
      liver BC and Lut levels in the LPC group were significantly higher than the other
      groups. The activity of BC 15,15'-monooxygenase in the intestinal mucosa of LPC
      and PC groups was higher than NoPL group. Plasma retinyl palmitate level in LPC
      (AUC, 647 +/- 89 pmol mL(-1) h(-1)) group was 2-fold higher than that of PC and
      NoPL groups. Results indicate that phospholipids enhanced the BC and Lut
      absorption. beta-Carotene uptake was not affected by Lut when given with micellar
      phospholipids, but reduced plasma Lut level was observed, which may be due to the
      conversion of absorbed Lut into its metabolites.

PMID- 19761894
TI  - Glutamine supplementation does not improve protein synthesis rate by the jejunal
      mucosa of the malnourished rat.
AB  - It has been demonstrated that glutamine, a conditionally essential amino acid,
      improves nitrogen balance, acts as a stimulant of protein synthesis, and
      decreases proteolysis in myopathic children. In contrast, other studies have
      shown no beneficial effect of glutamine supplementation on burn victims or
      critically ill patients. Nonetheless, we hypothesized that glutamine
      supplementation would increase the fractional protein synthesis rate (FSR) in the
      jejunal mucosa of malnourished male Wistar rats. Thus, the objective of the
      present study was to test the effect of daily oral glutamine supplementation
      (0.42 g kg(-1) d(-1) for 14 days) on the FSR of the jejunal mucosa of healthy and
      malnourished rats. A 4-hour kinetic study with l-[1-(13)C]leucine was
      subsequently performed, and jejunal biopsies were obtained 1.5 cm from the Treitz
      angle and analyzed. Malnourished rats showed a 25% weight loss and increased
      urinary nitrogen excretion. Plasma amino acid concentration did not differ
      between groups. (13)C enrichment in plasma and jejunal cells was higher in the
      malnourished groups than in the healthy group. The FSR (percent per hour) was
      similar for the control and experimental groups (P > .05), with a mean range of
      22%/h to 27%/h. Oral glutamine supplementation alone did not induce higher
      protein incorporation by the jejunal mucosa in malnourished rats, regardless of
      total food intake or the presence or absence of glutamine supplementation.

PMID- 19761895
TI  - Mulberry leaf extract restores arterial pressure in streptozotocin-induced
      chronic diabetic rats.
AB  - Free radical-induced vascular dysfunction plays a key role in the pathogenesis of
      vascular disease found in chronic diabetic patients. Morus alba (MA) leaf extract
      is promoted for good health especially in diabetic patients. Interestingly,
      antidiabetic and antioxidant activities of MA have been reported in experimental
      animals. Thus, the hypothesis of this study was that the long-term treatment with
      MA could improve vascular reactivity of chronic diabetic rats. To test this
      hypothesis, we examined the effect of long-term treatment with MA on the vascular
      responses to vasoactive agents in streptozotocin-induced chronic diabetic rats.
      The diabetic rats were either orally administered with distilled water, MA (0.25,
      0.5 and 1 g/kg per day) or subcutaneously injected with insulin (4 U/kg per day)
      for 8 weeks. After each treatment, the fasting blood glucose, blood pressure,
      vascular responses to vasoactive agents and tissue malondialdehyde were examined.
      Morus alba at the doses of 0.5 and 1 g/kg, which significantly reduced blood
      glucose level, also significantly decreased the high blood pressure in diabetic
      rats. Vascular responses of the chronic diabetic rats to vasodilators,
      acetylcholine (3-30 nmol/kg) and sodium nitroprusside (1-10 nmol/kg) were
      significantly suppressed by 26% to 44% and 45% to 77% respectively, whereas those
      to vasoconstrictor, phenylephrine (0.01-0.1 micromol/kg) were significantly
      increased by 23% to 38% as compared to normal rats. Interestingly, the
      administration of 0.5 and 1 g/kg MA or 4 U/kg insulin significantly restored the
      vascular reactivities of diabetic rats. Moreover, 8 weeks of diabetes resulted in
      the elevation of malondialdehyde content in tissues (liver, kidney, heart, and
      aorta), and MA treatment significantly lessened this increase. These results
      provide the first evidence for the efficacy of MA in restoring the vascular
      reactivity of diabetic rats, the mechanism of which may associate with the
      alleviation of oxidative stress.

PMID- 19761896
TI  - Orthognathic surgery in the 21st century: the dreamliner takes flight.

PMID- 19761897
TI  - Accelerated orthognathic surgery and increased orthodontic efficiency: a paradigm
      shift.

PMID- 19761898
TI  - A new reliable method for alveolar bone grafting at about 6 years of age.
AB  - When the timing of alveolar bone grafting is based on the eruptive progress of
      the permanent maxillary canine tooth, the surgical procedure is, by definition,
      delayed until the late mixed dentition phase. This treatment strategy overlooks
      both the crown length and the periodontal condition of the maxillary permanent
      incisors adjacent to the cleft defect. One should perform alveolar bone grafting
      at the time of eruption of the maxillary central incisor at about 5.5 to 6 years
      of age.

PMID- 19761899
TI  - Building nonhospital-based platforms for ambulatory orthognathic surgery:
      facility, anesthesia, and price considerations.

PMID- 19761900
TI  - Safe, efficient, and cost-effective orthognathic surgery in the outpatient
      setting.
AB  - There has been a dramatic decline in the number of orthognathic surgery cases
      over the past 15 to 20 years. This decrease is a result of several compounding
      factors including decreasing coverage by major medical insurance companies and
      increasing health care costs. The difficulty associated with making orthognathic
      surgery financially practical has turned the interest of many oral and
      maxillofacial surgeons away from orthognathic procedures. The combination of
      these factors has resulted in decreased availability of surgeons participating in
      the correction of dentofacial deformities and has forced orthodontists and
      patients, without surgical correction as an option, to settle for less-than-ideal
      treatment results. To reverse this trend and make surgery more affordable and
      available, surgeons must work to make surgical treatment more acceptable to
      patients. This can be accomplished in several ways. First, the oral and
      maxillofacial surgery profession must reinforce the importance and value of
      orthognathic surgery to insurance providers, patients, and referring clinicians,
      as well as to surgeons within our own specialty. Alternative methods for
      providing high-quality surgical services at a reasonable cost must be explored
      including providing options for cost-effective outpatient surgical care, making
      better arrangements for financial assistance, and exploring options to obtain
      coverage from third-party providers. Outpatient surgery in facilities that can
      substantially reduce cost can be an effective way of providing quality treatment
      that is affordable to patients. Efficient, safe, and effective outpatient
      orthognathic surgery will help patients benefit from this valuable service.

PMID- 19761901
TI  - The accredited cosmetic facial surgery office: a paradigm shift in oral and
      maxillofacial surgery.

PMID- 19761902
TI  - Three-dimensional treatment planning of orthognathic surgery in the era of
      virtual imaging.
AB  - PURPOSE: The aim of this report was to present an integrated 3-dimensional (3D)
      virtual approach toward cone-beam computed tomography-based treatment planning of
      orthognathic surgery in the clinical routine. MATERIALS AND METHODS: We have
      described the different stages of the workflow process for routine 3D virtual
      treatment planning of orthognathic surgery: 1) image acquisition for 3D virtual
      orthognathic surgery; 2) processing of acquired image data toward a 3D virtual
      augmented model of the patient's head; 3) 3D virtual diagnosis of the patient; 4)
      3D virtual treatment planning of orthognathic surgery; 5) 3D virtual treatment
      planning communication; 6) 3D splint manufacturing; 7) 3D virtual treatment
      planning transfer to the operating room; and 8) 3D virtual treatment outcome
      evaluation. CONCLUSIONS: The potential benefits and actual limits of an
      integrated 3D virtual approach for the treatment of the patient with a
      maxillofacial deformity are discussed comprehensively from our experience using
      3D virtual treatment planning clinically.

PMID- 19761903
TI  - New clinical protocol to evaluate craniomaxillofacial deformity and plan surgical
      correction.

PMID- 19761904
TI  - Three-dimensional imaging and computer simulation for office-based surgery.
AB  - PURPOSE: Advancements in computers and imaging, especially over the last 10
      years, have permitted the adoption of 3-dimensional imaging protocols in the
      health care field. In addition, the affordability and ease of use of these
      modalities allow their widespread adoption and use in diagnosis and treatment
      planning. This is particularly important when the deformities are complex
      involving both function and esthetics, such as those in the dentofacial area and
      with orthognathic surgery. MATERIALS AND METHODS: Image fusion involves combining
      images from different imaging modalities to create a virtual record of an
      individual called a patient-specific anatomic reconstruction (PSAR). We describe
      the system and show its use in 1 case. RESULTS: Image fusion and, more
      specifically, PSAR permit a more accurate analysis of deformity as an aid to
      diagnosis and treatment planning. CONCLUSION: Three-dimensional imaging and
      computer simulation can be effectively used for planning office-based procedures.
      The PSAR can be used to perform virtual surgery and establish a definitive and
      objective treatment plan for correction of a facial deformity. The end result is
      improved patient care and decreased expense.

PMID- 19761905
TI  - Use of computer-aided design and computer-aided manufacturing to produce
      orthognathically ideal surgical outcomes: a paradigm shift in head and neck
      reconstruction.

PMID- 19761906
TI  - Orthopedic traction of the maxilla with miniplates: a new perspective for
      treatment of midface deficiency.

PMID- 19761907
TI  - Speedy surgical orthodontic treatment with skeletal anchorage in adults--sagittal
      correction and open bite correction.
AB  - PURPOSE: The present report describes a new type of corticotomy-assisted
      orthodontic treatment called Speedy orthodontics, which allows faster movements
      of the dental segments using skeletal anchorage. MATERIALS AND METHODS: To
      minimize the risk of necrosis, 2 procedures are performed. During the initial
      surgery, bilateral and horizontal corticotomies are performed in the palatal area
      with the patient under local anesthesia. After 2 to 3 weeks, a second buccal
      corticotomy is performed and 500 to 900 g of force per side is immediately
      applied to the corticotomized segment. RESULTS: Successful alveolar bone bending
      can be obtained in cases of adult protrusion or open bite. CONCLUSIONS: Speedy
      orthodontics allows for more precise control of anterior segment retraction in
      adult protrusion patients and can be used for posterior segment intrusion. This
      technology is powerful, easy to apply, and provides a significant advance in
      surgical orthodontics.

PMID- 19761908
TI  - Accelerated osteogenic orthodontics technique: a 1-stage surgically facilitated
      rapid orthodontic technique with alveolar augmentation.
AB  - PURPOSE: Demineralization of a thin layer of bone over a root prominence after
      corticotomy surgery can optimize the response to applied orthodontic forces. This
      physiologic response is consistent with the regional acceleratory phenomenon
      process. When combined with alveolar augmentation, one is no longer strictly at
      the mercy of the original alveolar volume and osseous dehiscences, and
      fenestrations can be corrected over vital root surfaces. This is substantiated
      with computerized tomographic and histologic evaluations. Two case reports are
      presented that demonstrate the usefulness of the accelerated osteogenic
      orthodontics technique in de-crowding and space closing for the correction of
      dental malocclusions. MATERIALS AND METHODS: Orthodontics is combined with full
      thickness flap reflection, selective alveolar decortication, ostectomy, and bone
      grafting to accomplish complete orthodontic treatment. RESULTS: Rapid tooth
      movement was demonstrated in both cases and stability up to 8 years of retention.
      CONCLUSION: The accelerated osteogenic orthodontics technique provides for
      efficient and stable orthodontic tooth movement. Frequently, the teeth can be
      moved further in one third to one fourth the time required for traditional
      orthodontics alone. This is a physiologically based treatment consistent with a
      regional acceleratory phenomenon and maintaining an adequate blood supply is
      essential.

PMID- 19761909
TI  - Periodontal accelerated osteogenic orthodontics: a description of the surgical
      technique.

PMID- 19761910
TI  - Computer simulation and rapid prototyping for the reconstruction of the mandible.

PMID- 19761911
TI  - Clinical foundation for efficient treatment of obstructive sleep apnea.
AB  - Only a few decades ago, the entity known as obstructive sleep apnea (OSA) was
      unknown and untreated. Now, there is a rush to put literally millions of
      Americans on continuous positive airway pressure devices. Community practice
      standards are changing yearly under pressure from strong forces based on economic
      incentives for industry, government, and physicians, independent of the actual
      medical evidence supporting treatment and efficacy. Medicare has lowered the
      diagnostic threshold for diagnosis and reimbursement; the International
      Classification of Sleep Disorders, Revision 2 (2005) has allowed OSA to be
      diagnosed exclusively by a laboratory test without the patient having clinical
      symptoms of excessive daytime sleepiness; and industry is poised to have the
      public buy computer-assisted continuous positive airway pressure machines without
      need of a physician prescription. Because of this paradigm shift away from
      physician-directed diagnosis and treatment, this article will critically evaluate
      the present state of medical evidence regarding the clinical foundation for
      treatment of OSA.

PMID- 19761912
TI  - Diagnosis, treatment planning, and surgical correction of obstructive sleep
      apnea.
AB  - The aim of this report is to present the scientific rationale for considering
      maxillomandibular advancement as the surgical treatment of choice in selected
      patients with obstructive sleep apnea syndrome; review the treatment planning
      that will identify those patients who would benefit from this procedure; review
      the surgical techniques; and review the patient outcomes after maxillomandibular
      advancement surgery. Patients with obstructive sleep apnea syndrome who have
      demonstrable retropositioning of the maxilla and mandible should be informed of
      maxillomandibular advancement as the primary surgical treatment for obstructive
      sleep apnea syndrome.

PMID- 19761913
TI  - Transport distraction osteogenesis for reconstruction of the ramus-condyle unit
      of the temporomandibular joint: surgical technique.

PMID- 19761914
TI  - Characteristics and corrective outcome of face asymmetry by orthognathic surgery.
AB  - PURPOSE: This study was conducted to identify the characteristics of facial
      asymmetry before surgery and to evaluate the facial skeletal changes and
      stability after 2-jaw orthognathic surgery. The ideal "double-cross grid" as
      fitting the key landmarks to the reference planes on posteroanterior cephalograms
      was set as the treatment goal. PATIENTS AND METHODS: Twenty-seven adult patients,
      18 female and 9 male subjects, were evaluated before and after surgery and at
      completion of orthodontic treatment. Cephalometric measurements of
      posteroanterior and lateral cephalograms were obtained at 3 timings. Measurements
      of frontal facial photographs were recorded before and after treatment. Data from
      each time set were compared to evaluate surgical achievement and postsurgical
      stability. RESULTS: All patients had original malocclusion of Class III in at
      least 1 side of the dentition except 1 patient. Total treatment duration was 15
      +/- 3.5 months on average. Laterality of the patients demonstrated left-side
      dominance in 18 patients and right-side dominance in 9 patients. After surgery,
      face symmetry was improved by correction of the occlusal plane cant, incisal
      dental axis, and chin deviation. Symmetry of bilateral gonial width was also
      improved significantly with good stability. Intergonial width was reduced by 3.4
      mm during treatment. Soft tissue presented similar correction by leveling oral
      commissures and correcting chin deviation. The maxilla was moved forward 1.25 mm
      and upward 1.20 mm, and the mandible was setback 4.3 mm and upward 1.5 mm as
      measured from lateral cephalograms. All sagittal changes remained stable after
      surgery. CONCLUSION: Fitting skeletal landmarks into a double-cross grid on
      posteroanterior cephalogram is an attainable guide and goal for 2-jaw
      orthognathic correction of facial asymmetry. Symmetry was achieved and facial
      profile was improved after surgery and remained stable afterward. The decrease of
      intergonial width indicated considerable remodeling of the bilateral gonial angle
      after surgery.

PMID- 19761915
TI  - Effect on maxillary arch development of early 2-stage palatoplasty by modified
      furlow technique and conventional 1-stage palatoplasty in children with complete
      unilateral cleft lip and palate.
AB  - PURPOSE: The purpose of this study was to evaluate the palatal morphology of
      patients with complete unilateral cleft lip and palate after early 2-stage
      palatoplasty (ETS) consisting of soft palate closure by a modified Furlow
      palatoplasty at 12 months of age and hard palate closure at 18 months of age. We
      compared the result with the palatal morphology obtained by Wardill-Kilner push
      back palatoplasty (PB) at 12 months of age with that of children with noncleft
      palate. In the present study we investigated whether ETS can result in better
      palatal development than conventional PB. MATERIALS AND METHODS: Thirty subjects
      were treated by ETS and 42 underwent PB. We also included cross-sectional data
      obtained from 66 children with noncleft palate as control. We measured the arch
      length, width, and cleft width using dental cast models that were consecutively
      taken at 3 months to 4 yrs of age and compared the results among the 3 groups.
      RESULTS: At 4 years of age, the anteroposterior palatal length of ETS was
      significantly longer than that of PB by 9.8%, and the transversal palatal width
      of ETS was also markedly wider than that of PB at every point measured.
      Furthermore, ETS showed potential catch-up growth in the anteroposterior palatal
      length from 12 months to 4 years of age. CONCLUSION: These results demonstrate
      that ETS has a considerable benefit for the palatal development of patients with
      complete unilateral cleft lip and palate compared with PB.

PMID- 19761916
TI  - Clinical review of factors leading to perioperative dissatisfaction related to
      orthognathic surgery.
AB  - PURPOSE: The purpose of the study was to obtain information on factors leading to
      perioperative dissatisfaction of patients who undergo orthognathic surgery for
      dentofacial deformities. MATERIALS AND METHODS: A total of 44 patients who
      underwent orthognathic surgery between January 1, 2003, and September 30, 2005,
      were included in this study. All patients completed 21-item questionnaires, which
      were analyzed using the frequency distribution and the chi(2) test. RESULTS: The
      patients lost 6.4% of their body weight after 1-jaw surgery and 6.7% after 2-jaw
      surgery. The patients returned to their everyday life 4.8 weeks after 1-jaw
      surgery and 5.2 weeks after 2-jaw surgery. Restoration of sensory function after
      jaw surgery required almost 10 weeks. CONCLUSION: Written information about
      possible sequelae and the recovery period and patients' consent to the surgical
      procedure may be helpful in proper communication, which may reduce patients'
      perioperative dissatisfaction.

PMID- 19761917
TI  - Postoperative nasal forms after presurgical nasoalveolar molding followed by
      medial-upward advancement of nasolabial components with vestibular expansion for
      children with unilateral complete cleft lip and palate.
AB  - PURPOSE: The management for primary unilateral cleft lip nose deformities has not
      yet been established. In this study, short-term postoperative nasal forms after
      presurgical nasoalveolar molding (NAM) followed by primary lip repair for
      children with complete unilateral cleft lip and palate (UCLP) were evaluated and
      compared with the nasal forms achieved by treatment without nose correction.
      PATIENTS AND METHODS: Fifteen patients with complete UCLP who were treated in our
      department and followed up for more than 1 year (range 1 to 5 yrs) were enrolled.
      All subjects underwent presurgical orthopedic treatment with NAM, followed by lip
      repair using Cronin's triangular flap method with medial-upward advancement of
      nasolabial components with vestibular expansion. Postoperative nasal forms
      including nostril height and width ratio, ratio of the height of the top of the
      alar groove, and curvature of the appropriate circle of the nasal ala were
      evaluated using color photographs. Fifteen patients with complete UCLP who
      underwent presurgical orthopedic treatment using a Hotz plate followed by lip
      repair without nose correction served as controls. RESULTS: The comparison of
      postoperative nasal forms demonstrated that the nostril height and width ratio
      and the height of the top of the alar groove in the correction group were
      significantly superior compared with those of the controls. CONCLUSIONS: Our
      management of cleft lip nose will provide good nasal forms with minimum invasion
      in patients with UCLP. Long-term follow-up will be necessary to clarify effects
      on the growth of nasal tissues reconstructed in infancy.

PMID- 19761918
TI  - Mandibular traction--an alternative treatment in infants with Pierre Robin
      sequence.
AB  - PURPOSE: In the Pierre Robin sequence, retrognathia and glossoptosis lead to
      airway obstruction in infants with or without cleft palate. Mandibular
      distraction has gained acceptance for the treatment of airway obstruction.
      However, surgical interventions can result in complications. In our institution,
      mandibular traction is the standard treatment in cases of severe respiratory
      distress. PATIENTS AND METHODS: A retrospective study was performed of all
      infants treated for Pierre Robin sequence at our institution from 1979 to 2007.
      The diagnosis and type of treatment (positioning/palatal plate or mandibular
      traction) were evaluated. The palatal plate had several knobs at the anterior
      alveolar ridge to direct the tongue forward. Mandibular traction was applied
      using weights transmitted onto the mandible by a custom-made plate fixed at the
      mandible with circumferential wiring. RESULTS: Nineteen children required airway
      treatment because of repeated cyanotic episodes and respiratory adaptation
      disorders. Of these 19 children, 8 had been diagnosed with pure Pierre Robin
      sequence and 11 also had other congenital abnormalities. Of the 19 patients, 10
      (56%) were treated nonoperatively by lateral or prone positioning and/or wearing
      a palatal plate to stimulate the tongue. In 8 patients, conservative management
      was not sufficient, and continuous mandibular traction was performed for 2 to 5
      weeks using weights of 50 to 200 g. One patient required a tracheostomy because
      of tracheomalacia. CONCLUSIONS: Surgical therapy using mandibular traction is a
      minimally invasive alternative to more invasive procedures because no serious
      complications such as scars or damage to the nerves were encountered.

PMID- 19761919
TI  - Changes of mandibular movement tracings after the correction of mandibular
      protrusion by bilateral sagittal split ramus osteotomy.
AB  - PURPOSE: We investigated the effects on mandibular movement tracings after the
      correction of mandibular protrusion by bilateral sagittal split ramus osteotomy
      (BSSRO). PATIENTS AND METHODS: This study was comprised of 30 control subjects
      and 14 mandibular protrusion patients. Mandibular movements were recorded during
      opening, protrusion, and laterotrusion of the jaw with the ARCUSdigma 3
      dimensional mandibular kinesiograph (KaVo Dental, Biberach, Germany). The
      kinematic center and incisor point were used as reference points. RESULTS: The
      mandibular movement tracings of patients before the correction of mandibular
      protrusion by BSSRO were significantly different from those in subjects in the
      control group, whereas there were no significant differences between the
      mandibular movement tracings after the correction of mandibular protrusion by
      BSSRO and those in the control group. Furthermore, the mean biases of the
      condylar kinematic center in the 3-dimensional directions during the opening,
      protrusive, and laterotrusive movements of the jaws in the preoperative group
      were smaller than those in the postoperative group (P < .05), which were similar
      to those in the control group (P > .05). CONCLUSION: After correction by BSSRO,
      the mandibular movement tracings in mandibular protrusion patients will be
      altered to be similar to those in subjects in the control group, which we believe
      might support the return of mandibular functional movements in treated patients.

PMID- 19761920
TI  - A simple mechanism for measuring and adjusting distraction forces during
      maxillary advancement.
AB  - PURPOSE: Direct measurement of distraction forces on the craniofacial skeleton
      has never been reported. The present report describes the development of a method
      of assessing and adjusting traction forces applied through maxillary distraction
      osteogenesis. MATERIALS AND METHODS: A simple mechanism to measure and adjust
      tension force during maxillary distraction osteogenesis was developed and
      connected bilaterally to the traction screws of a rigid external distraction
      device. Measurements were carried out before and after activation using a Shimpo
      (Nidec-Shimpo America Corporation, Itasca, IL) force gauge in 4 patients (2 with
      unilateral cleft lip and/or palate, 1 with bilateral cleft lip and palate, and 1
      with noncleft) during the distraction process. Activation was performed twice a
      day at a rate of 1 mm/day. RESULTS: The average maximum force applied throughout
      the distraction period was 42.5 N (range 16.4 to 65.3 N), with increments, after
      activation, averaging 10.5 N (range 7.9 to 15.7 N). In patients with unilateral
      cleft lip and/or palate, distraction forces on the larger segment were 65.1%
      higher than on the lesser segment. A differential pattern of forces was also
      observed in the patients with asymmetric noncleft. However, the differential
      forces between lateral segments were not observed in the patient with bilateral
      cleft lip and palate. During the activation period, distraction forces
      progressively increased, whereas the amount of maxillary movement decreased. Pain
      and discomfort were reported with high forces. CONCLUSIONS: Through this
      mechanism, direct measurement and adjustment of distraction forces during
      maxillary advancement was possible. The unbalanced pattern of forces observed in
      patients with cleft suggests the necessity of individual adjustments for
      controlling pain and clinical symptoms. Accordingly, assessment of distraction
      forces during maxillary distraction osteogenesis is extremely helpful in
      understanding the biomechanics of the distraction process.

PMID- 19761921
TI  - Effects of transmandibular symphyseal distraction on teeth, bone, and
      temporomandibular joint.
AB  - PURPOSE: The aim of this clinical study was to investigate the clinical effects
      and long-term results of the transmandibular symphyseal distraction technique for
      the correction of mandibular transverse deficiencies. This was achieved by
      assessing the dental, skeletal, and temporomandibular joint changes in the
      sagittal, vertical, and axial planes using cephalograms, dental casts, and
      computed tomography (CT). PATIENTS AND METHODS: Seven patients with mandibular
      transverse deficiencies (3 females and 4 males), aged 14.3 to 22.5 years (mean
      16.2), were treated with a bone-borne transmandibular distractor. Lateral and
      posteroanterior cephalometric films, CT scans of both temporomandibular joints,
      and dental casts were obtained preoperatively, at the end of the distraction
      period, and at the end of 3 years (clinical follow-up period). The clinical
      findings were assessed according to the morphologic and functional success
      criteria established by the Steering Group of European Collaboration on Cranial
      Facial Anomalies for patients with developmental dentofacial anomalies undergoing
      craniofacial distraction osteogenesis. The statistical analysis of cephalometric
      films and dental cast measurements was done using the paired t test. The mean
      postoperative examination period was 40 months (range 36 to 48). RESULTS: The
      desired amount of distraction was achieved in all patients (mean 6.48 mm). The
      intraoperative and postoperative complications encountered included damage to the
      central incisors during vertical osteotomy (1 patient), wound dehiscence after a
      latent period (3 patients), mild temporomandibular joint pain during the
      distraction period (3 patients), and chronic gingivitis around the activation
      rods (7 patients). The success criteria for craniofacial distraction osteogenesis
      were fulfilled at the end of the 3-year follow-up period. Model analysis showed
      that the maximal amount of expansion was achieved at the premolar region (first
      premolar 5.79 mm, second premolar 5.07 mm). Frontal (posteroanterior)
      cephalograms taken at the end of the distraction period revealed significant
      increases in the bicondylar (0.35 mm), bigonion (3.43 mm), biantegonion (2.29
      mm), and intermolar (4.0 mm) widths, and the ramal angle had decreased
      significantly (-1.64 degrees). The increase in the transverse measurements was
      greater at the dentoalveolar level than at the base of the mandible. Lateral
      cephalograms showed that transmandibular symphyseal distraction produced
      significant increases in the incisor mandibular plane angle (2.79 degrees) and
      mandibular body length (1.72 mm). The effect of the procedure on the condyle was
      2.5 degrees to 3 degrees of distolateral rotation as calculated using the CT
      scans. Dental crowding was resolved rapidly by the movement of the teeth into the
      distraction regenerate. CONCLUSIONS: The clinical and radiologic results of the
      present study have shown that a transmandibular distractor is a clinically
      effective bone-borne distractor for the correction of mandibular transverse
      deficiencies and anterior crowding. The follow-up cephalograms and CT scans
      showed the transverse skeletal stability of the distraction procedure and no
      permanent temporomandibular dysfunction. However, additional multicenter studies
      with more patients are necessary to precisely evaluate the long-term
      postdistraction changes on the skeleton, teeth, and temporomandibular joint.

PMID- 19761922
TI  - Modified animal model and computer-assisted approach for dentoalveolar
      distraction osteogenesis to reconstruct unilateral maxillectomy defect.
AB  - PURPOSE: The purpose of this report is to show the establishment of an animal
      model with a unilateral maxilla defect, application of virtual reality and rapid
      prototyping in the surgical planning for dentoalveolar distraction osteogenesis
      (DO). MATERIALS AND METHODS: Two adult dogs were used to develop an animal model
      with a unilateral maxillary defect. The 3-dimensional model of the canine
      craniofacial skeleton was reconstructed with computed tomography data using the
      software Mimics, version 12.0 (Materialise Group, Leuven, Belgium). A virtual
      individual distractor was designed and transferred onto the model with the
      defect, and the osteotomies and distraction processes were simulated. A precise
      casting technique and numeric control technology were applied to produce the
      titanium distraction device, which was installed on the physical model with the
      defect, which was generated using Selective Laser Sintering technology, and the
      in vitro simulation of osteotomies and DO was done. RESULTS: The 2 dogs survived
      the operation and were lively. The osteotomies and distraction process were
      simulated successfully whether on the virtual or the physical model. The bone
      transport could be distracted to the desired position both in the virtual
      environment and on the physical model. CONCLUSIONS: The novel method to develop
      an animal model with a unilateral maxillary defect was feasible, and the animal
      model was suitable to develop the reconstruction method for unilateral maxillary
      defect cases with dentoalveolar DO. Computer-assisted surgical planning and
      simulation improved the reliability of the maxillofacial surgery, especially for
      the complex cases. The novel idea to reconstruct the unilateral maxillary defect
      with dentoalveolar DO was proved through the model experiment.

PMID- 19761923
TI  - Does hyoid bone resection according to Sistrunk influence normal craniofacial
      growth? A cephalometric study.
AB  - PURPOSE: To retrospectively evaluate the influence of hyoid bone resection
      according to Sistrunk in early age due to a thyroglossal duct cyst on
      craniofacial growth. MATERIALS AND METHODS: We retrospectively examined 10
      patients (2 females and 8 males) having had hyoid bone resection according to
      Sistrunk due to thyroglossal duct cysts by lateral cephalograms taken before
      orthodontic treatment (mean, 17.1 years; range, 8.6-31.9 years). Surgery was
      carried out at a mean age of 4.4 years (range, 0.37-9.8 years). All lateral
      cephalograms were evaluated and traced by hand. Descriptive statistics were
      calculated, and data from each patient were compared individually with
      corresponding standard values (age and gender) from Bathia and Leighton. RESULTS:
      With regard to sagittal parameters, the SNB angles were by trend too small and
      the ANB angles were too large. However, the ratio of mandibular to maxillary
      length showed that the patients had a mandible that was too large or maxilla that
      was too small. With regard to vertical parameters, large deviations from normal
      values in both directions (hyperdivergent to hypodivergent pattern) could be
      detected when we analyzed NSL/ML', NL/ML', and NSL/NL. With regard to dental
      parameters, the majority of the patients had retroclined upper (IsL/NL, IsL/N-A)
      and lower (IiL/ML, IiL/N-B) incisors. CONCLUSIONS: Several vertical and
      horizontal skeletal and dental cephalometric parameters were shown to be
      different by trend when compared with control values. A possible negative impact
      on craniofacial growth potential and direction as a result of hyoid resection in
      early age according to Sistrunk cannot be excluded.

PMID- 19761924
TI  - The effect of maxillary multidirectional movement on nasal respiration.
AB  - PURPOSE: Deformities of the maxilla may exist on all planes, and we treat these
      problems by mobilizing and repositioning the maxilla on all planes. Some authors
      have examined the effects of maxillary movement on the nasal airway. In clinical,
      practice, active anterior rhinomanometry is the most reliable and frequently used
      method to assess nasal respiratory function. The purpose of this study was to
      evaluate changes in nasal airflow and nasal airway resistance after maxillary
      movement performed by active anterior rhinomanometry. MATERIALS AND METHODS: We
      studied 25 patients (18 female patients and 7 male patients; aged 16-30 years) in
      this clinical trial. Three days before surgery and 6 months after surgery, after
      a rest period of 30 minutes, active anterior rhinomanometry with a tube was
      performed at a fixed transnasal pressure of 150 Pa. The surgical treatment plan
      included bimaxillary surgery consisting of a 1-piece Le Fort I osteotomy combined
      with a bilateral sagittal split osteotomy. Mean and median total nasal airflow
      and nasal resistance rate were calculated before surgery and after surgery and
      compared by use of SPSS software (version 11.5; SPSS, Chicago, IL) and paired t
      test. RESULTS: An increase in nasal airflow (P = .009) and a decrease in nasal
      resistance (P = .022) were observed in the maxillary impaction and advancement
      group. In the maxillary impaction and setback group, there was a significant
      difference in nasal resistance changes (P = .027); however, postsurgical nasal
      airflow compared with presurgical values showed no statistically significant
      difference (P = .244). CONCLUSION: Impaction and advancement of the maxilla can
      improve nasal respiratory function, but maxillary impaction and setback reduce
      nasal respiratory function. Hence candidates for maxillary impaction and setback
      must be informed about decreased nasal respiratory function.

PMID- 19761925
TI  - Comparison of bipartite versus tripartite osteotomy for maxillary transversal
      expansion using 3-dimensional preoperative and postexpansion computed tomography
      data.
AB  - PURPOSE: To evaluate tripartite paramedian versus bipartite median osteotomy in
      surgically assisted rapid maxillary expansion. Tripartite osteotomy was performed
      between the lateral incisors and canines at the former premaxillary junction to
      avoid midline diastema, septal and columellar dislocation, and asymmetric
      expansion, minimizing high-distraction forces through bilateral doubled osteotomy
      on periodontia and thus reducing vestibular attachment loss and producing stable
      callus formation to avoid relapse. PATIENTS AND METHODS: The preoperative and
      postexpansion computed tomography data from 50 patients were analyzed in
      multiplanar viewing for bodily segment movement, vestibular bone loss, and
      transverse skeletal and dental widening with predefined landmarks. Of the 50
      patients, 22 had undergone tripartite and 28 had undergone bipartite osteotomy.
      RESULTS: Using an independent t test, both osteotomies permitted adequate
      transverse skeletal expansion in the premolars, converging, however, in the
      molars. Bipartite osteotomy resulted in less symmetry in transverse skeletal
      widening, greater bodily segment movement in the first premolar/molar, and
      greater vestibular bone loss. Tripartite osteotomy resulted in greater overall
      expansion and less bone remodeling. On variance analysis, tripartite bone-borne
      distraction resulted in the greatest decrease of transverse expansion in patients
      older than 20 years. The tripartite osteotomy also provoked distractor- and age
      independent outward segmental movement. Bipartite osteotomy resulted in
      distractor- and age-independent inward segmental movement. Bipartite osteotomy
      showed the greatest bone resorption in patients younger than 20 years old in the
      molars and tripartite osteotomy in patients older than 20 years in the premolars.
      CONCLUSIONS: Tripartite paramedian osteotomy allowed greater overall symmetric
      expansion compared with bipartite median osteotomy, with, however, a decline in
      transverse widening to the posterior. Bipartite osteotomy should be preferred
      whenever good periodontal status permits greater vestibular bone loss and a
      midline diastema and asymmetric expansion and a midline shift will be tolerated
      by the patient. Tripartite osteotomy should be chosen whenever a midline diastema
      and shift, septal and columellar dislocation, asymmetric expansion, and larger
      distraction forces on the paradontia, resulting in vestibular attachment loss,
      are to be avoided.

PMID- 19761926
TI  - Modified 2-flap technique in the correction of the wide "circumflex"-shaped
      incomplete cleft palate.

PMID- 19761927
TI  - Alternative method to reposition the dislocated transport segment during vertical
      alveolar distraction.

PMID- 19761928
TI  - Partial facial hemihyperplasia with unusual soft tissue anomalies: long-term
      follow-up.

PMID- 19761929
TI  - An alternative technique for genioglossus muscle advancement in phase I surgery
      in the treatment of obstructive sleep apnea.

PMID- 19761930
TI  - Neural activity-induced modulation of BOLD poststimulus undershoot independent of
      the positive signal.
AB  - Despite intense research on the blood oxygenation level-dependent (BOLD) signal
      underlying functional magnetic resonance imaging, our understanding of its
      physiological basis is far from complete. In this study, it was investigated
      whether the so-called poststimulus BOLD signal undershoot is solely a passive
      vascular effect or actively induced by neural responses. Prolonged static and
      flickering black-white checkerboard stimulation with isoluminant grey screen as
      baseline condition were employed on eight human subjects. Within the same region
      of interest, the positive BOLD time courses for static and flickering stimuli
      were identical over the entire stimulus duration. In contrast, the static stimuli
      exhibited no poststimulus BOLD signal undershoot, whereas the flickering stimuli
      caused a strong BOLD poststimulus undershoot. To ease the interpretation, we
      performed an additional study measuring both BOLD signal and cerebral blood flow
      (CBF) using arterial spin labeling. Also for CBF, a difference in the
      poststimulus period was found for the two stimuli. Thus, a passive blood volume
      effect as the only contributor to the poststimulus undershoot comes short in
      explaining the BOLD poststimulus undershoot phenomenon for this particular
      experiment. Rather, an additional active neuronal activation or deactivation can
      strongly modulate the BOLD poststimulus behavior. In summary, the poststimulus
      time course of BOLD signal could potentially be used to differentiate neuronal
      activity patterns that are otherwise indistinguishable using the positive evoked
      response.

PMID- 19761931
TI  - Regadenoson: a new myocardial stress agent.
AB  - Vasodilator stress myocardial perfusion imaging (MPI) accounts for up to 50% of
      all stress MPI studies performed in the U.S. In 2008, the Food and Drug
      Administration approved regadenoson for stress testing in conjunction with MPI.
      Regadenoson, unlike adenosine, is a selective A(2A) agonist that is given as an
      intravenous bolus at a fixed dose, with less undesirable side effects including
      atrioventricular block and bronchospasm. Unlike adenosine, regadenoson could be
      used in patients with mild-to-moderate reactive airway disease. This review will
      summarize the pre-clinical and clinical data on regadenoson, as they specifically
      relate to its use as a vasodilator stress agent, currently the only approved
      selective A(2A) agonist.

PMID- 19761932
TI  - Incidence and management of restenosis after treatment of unprotected left main
      disease with drug-eluting stents 70 restenotic cases from a cohort of 718
      patients: FAILS (Failure in Left Main Study).
AB  - OBJECTIVES: This study sought to retrospectively appraise the incidence and
      management of restenosis after drug-eluting stent (DES) implantation for
      unprotected left main (ULM) disease. BACKGROUND: The promising role of DES for
      ULM has been reported. However, no detailed data are available on subsequent
      restenosis. METHODS: From the total sample of patients with ULM treated with DES,
      we identified those presenting with angiographic ULM restenosis. The primary end
      point was the long-term rate of major adverse cardiac events (MACE), that is,
      death, myocardial infarction (MI), or target lesion revascularization (TLR). We
      also adjudicated stent thrombosis according to the Academic Research Consortium.
      RESULTS: Post-DES restenosis in ULM occurred in 70 of 718 patients (9.7%). Of
      these, 59 (84.3%) were treated percutaneously (34 [48.6%] with additional DES, 22
      [31.4%] with standard or cutting balloons, 2 [2.9%] with rotational atherectomy,
      and 1 [1.4%] with a bare-metal stent), whereas 7 (10%) patients underwent bypass
      surgery and 4 (5.7%) were treated medically. In-hospital MACE included no
      periprocedural MI and only 1 (1.4%) death. After 27.2 +/- 15.4 months, MACE
      occurred cumulatively in 18 (25.7%) patients, with death in 4 (5.7%), MI in 2
      (2.9%), and TLR in 15 (21.4%). Patients treated with medical, interventional, and
      surgical therapy had the following MACE rates, respectively: 50%, 25.4%, and
      14.3%. Definite, probable, and possible stent thrombosis occurred in 0 (0%), 1
      (1.4%), and 1 (1.4%) patient, respectively. CONCLUSIONS: DES restenosis in the
      ULM artery can be managed in most cases with a minimally invasive approach,
      achieving favorable early and late results.

PMID- 19761934
TI  - The best "model system" for human (coronary arteries) is human.

PMID- 19761933
TI  - The alpha-1D Is the predominant alpha-1-adrenergic receptor subtype in human
      epicardial coronary arteries.
AB  - OBJECTIVES: The goal was to identify alpha-1-adrenergic receptor (AR) subtypes in
      human coronary arteries. BACKGROUND: The alpha1-ARs regulate human coronary blood
      flow. The alpha1-ARs exist as 3 molecular subtypes, alpha1A, alpha1B, and
      alpha1D, and the alpha1D subtype mediates coronary vasoconstriction in the mouse.
      However, the alpha1A is thought to be the only subtype in human coronary
      arteries. METHODS: We obtained human epicardial coronary arteries and left
      ventricular (LV) myocardium from 19 transplant recipients and 6 unused donors
      (age 19 to 70 years; 68% male; 32% with coronary artery disease). We cultured
      coronary rings and human coronary smooth muscle cells. We assayed alpha1- and
      beta-AR subtype messenger ribonucleic acid (mRNA) by quantitative real-time
      reverse transcription polymerase chain reaction and subtype proteins by
      radioligand binding and extracellular signal-regulated kinase (ERK) activation.
      RESULTS: The alpha1D subtype was 85% of total coronary alpha1-AR mRNA and 75% of
      total alpha1-AR protein, and alpha1D stimulation activated ERK. In contrast, the
      alpha1D was low in LV myocardium. Total coronary alpha1-AR levels were one-third
      of beta-ARs, which were 99% the beta2 subtype. CONCLUSIONS: The alpha1D subtype
      is predominant and functional in human epicardial coronary arteries, whereas the
      alpha1A and alpha1B are present at very low levels. This distribution is similar
      to the mouse, where myocardial alpha1A- and alpha1B-ARs mediate beneficial
      functional responses and coronary alpha1Ds mediate vasoconstriction. Thus,
      alpha1D-selective antagonists might mediate coronary vasodilation, without the
      negative cardiac effects of nonselective alpha1-AR antagonists in current use.
      Furthermore, it could be possible to selectively activate beneficial myocardial
      alpha1A- and/or alpha1B-AR signaling without causing coronary vasoconstriction.

PMID- 19761935
TI  - Comparison of omeprazole and pantoprazole influence on a high 150-mg clopidogrel
      maintenance dose the PACA (Proton Pump Inhibitors And Clopidogrel Association)
      prospective randomized study.
AB  - OBJECTIVES: This study sought to compare the effect of 2 proton pump inhibitors
      (PPIs) on platelet response to clopidogrel after coronary stenting for non-ST
      segment elevation acute coronary syndrome (NSTE ACS). BACKGROUND: Use of
      omeprazole has been reported to significantly decrease the clopidogrel
      antiplatelet effect because of cytochrome P450 interaction. Because all PPIs are
      metabolized by CYP2C19, but to a varying degree, we hypothesized that the
      reported negative omeprazole-clopidogrel drug interaction may not be caused by a
      class effect. METHODS: A total of 104 patients undergoing coronary stenting for
      NSTE ACS were prospectively included and randomized to omeprazole or pantoprazole
      20 mg. They received at discharge 75-mg aspirin and 150-mg clopidogrel. Platelet
      reactivity index (PRI) vasoactive stimulated phosphoprotein (VASP) was used to
      assess clopidogrel response and adenosine diphosphate (ADP)-induced aggregation
      for platelet reactivity (ADP-Ag). RESULTS: After 1 month, patients receiving
      pantoprazole had a significantly better platelet response to clopidogrel as
      assessed with the PRI VASP: 36 +/- 20% versus 48 +/- 17% (p = 0.007). We
      identified more clopidogrel nonresponders in the omeprazole group than in the
      pantoprazole group: 44% versus 23% (p = 0.04), odds ratio: 2.6 (95% confidence
      interval: 1.2 to 6.2). Conversely, we did not observe any significant difference
      in platelet reactivity with ADP-Ag between the omeprazole and pantoprazole
      groups: 52 +/- 15% and 50 +/- 18%, respectively (p = 0.29). CONCLUSIONS: The
      present findings suggest the preferential use of pantoprazole compared with
      omeprazole in patients receiving clopidogrel to avoid any potential negative
      interaction with CYP2C19.

PMID- 19761936
TI  - Baseline heart rate, antihypertensive treatment, and prevention of cardiovascular
      outcomes in ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial).
AB  - OBJECTIVES: The aim of this study was to evaluate the effect of baseline heart
      rate on the efficacy of atenolol-based compared with amlodipine-based therapy in
      patients with hypertension uncomplicated by coronary heart disease in the ASCOT
      BPLA (Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm).
      BACKGROUND: Heart rate is an established risk factor for cardiovascular events.
      Consequently, it is a widely held belief that beta-blockers should be prescribed
      for management of hypertension in patients with higher heart rates. METHODS:
      Patients with atrial fibrillation or taking rate-limiting antihypertensive drugs
      at baseline were excluded. Primary analyses used Cox models to investigate the
      potential attenuation of the treatment effect with higher baseline heart rate on
      total cardiovascular events and procedures (TCVP) via introduction of an
      interaction term. Secondary analyses assessed coronary and total stroke outcomes.
      RESULTS: Primary unadjusted analyses included 12,759 patients and 1,966 TCVP. At
      the final visit, mean heart rate reduction from baseline was 12.0 (SD 13.7) and
      1.3 (SD 12.1) beats/min in atenolol- and amlodipine-based groups, respectively.
      There was a reduction in TCVP in those allocated amlodipine-based therapy
      compared with atenolol-based therapy (unadjusted hazard ratio: 0.81, p < 0.001).
      This benefit was unattenuated at higher heart rates (interaction p value = 0.81).
      Similar results were obtained for coronary and total stroke outcomes.
      CONCLUSIONS: There was no evidence that the superiority of amlodipine-based over
      atenolol-based therapy for patients with hypertension uncomplicated by coronary
      heart disease was attenuated with higher baseline heart rate. These data suggest
      that, in similar hypertensive populations without previous or current coronary
      artery disease, higher baseline heart rate is not an indication for preferential
      use of beta-blocker-based therapy.

PMID- 19761937
TI  - Beta-blockers as first-line antihypertensive therapy the crumbling continues.

PMID- 19761938
TI  - Normal plasma levels of cardiac troponin I measured by the high-sensitivity
      cardiac troponin I access prototype assay and the impact on the diagnosis of
      myocardial ischemia.
AB  - OBJECTIVES: This study sought to evaluate the analytical and clinical performance
      of the novel hypersensitive cardiac troponin I (cTnI) prototype assay from
      Beckman Coulter (Fullerton, California). BACKGROUND: Studies on patients with
      acute coronary syndromes and on seemingly healthy subjects have shown that even
      very minor elevations of cardiac troponins are associated with an increased risk
      of death. However, the normal plasma levels of cardiac troponins are still not
      known. METHODS: cTnI plasma levels were measured in 542 healthy subjects, 319 men
      (age 59.9 +/- 11.8 years) and 213 women (age 59.8 +/- 13.1 years), and in 1,503
      randomly selected patients of the GUSTO IV (Global Utilization of Strategies To
      open Occluded arteries IV) cohort with unstable angina and non-ST-segment
      elevation myocardial infarctions (MIs). RESULTS: The cTnI levels at 10%
      coefficient of variation and 20% coefficient of variation imprecision were 0.0033
      and 0.0016 microg/l, respectively. The cTnI levels were measurable in >95% of the
      healthy subjects. The median level of healthy subjects <60 years of age was
      0.0032 microg/l (range 0.0011 to 0.0079 microg/l) with the 99th percentile being
      0.010 microg/l. No sex differences were observed. A receiver-operator
      characteristic curve analysis showed an optimal discrimination between healthy
      subjects and patients at 0.0064 microg/l with a sensitivity of 84.8% (95%
      confidence interval: 82.8% to 86.6%) and specificity of 89.7% (95% confidence
      interval: 86.8% to 92.2%). Outcomes as to death and/or MI were significantly
      different at this level (p < 0.01) in the GUSTO IV cohort. CONCLUSIONS: The novel
      high-sensitivity cTnI prototype assay from Beckman Coulter allows for the first
      time the measurement of cTnI levels in almost all healthy subjects. Our data
      indicate that the assay may be a powerful aid in the diagnosis and outcome
      prediction of patients with suspected myocardial ischemia and question any
      definition of myocardial infarction.

PMID- 19761939
TI  - Highly sensitive troponins the answer or just more questions?

PMID- 19761941
TI  - Cardiovascular disease in adult and pediatric HIV/AIDS.

PMID- 19761940
TI  - Association of chronic kidney disease with the spectrum of ankle brachial index
      the CHS (Cardiovascular Health Study).
AB  - OBJECTIVES: This study sought to determine the association of chronic kidney
      disease (CKD) with high ankle brachial index (ABI) measurement and to compare its
      strength with that of CKD with a low ABI. BACKGROUND: CKD is an important risk
      factor for cardiovascular disease (CVD) events. A high ABI, a marker of lower
      extremity arterial stiffness, is associated with CVD events and mortality. The
      association between CKD and high ABI is unknown. METHODS: The CHS (Cardiovascular
      Health Study) enrolled community-living people >65 years of age and measured
      kidney function and ABI. Glomerular filtration rate (GFR) was estimated using
      equations that incorporated either cystatin C or creatinine, and CKD was defined
      by estimated GFR <60 ml/min/1.73 m(2). The ABI was categorized as low (<0.90),
      low-normal (0.90 to 1.09), normal (1.10 to 1.40), and high (>1.40 or
      incompressible). Multinomial logistic regression was used to evaluate the
      associations of CKD with ABI categories. RESULTS: Among 4,513 participants, 23%
      had CKD, 13% had a low ABI, and 3% had a high ABI. In models adjusted for age,
      sex, race, hypertension, diabetes, smoking, body mass index, low-density
      lipoprotein cholesterol, high-density lipoprotein cholesterol, and C-reactive
      protein, cystatin C-based CKD was associated with both low ABI (relative risk
      [RR]: 2.0; 95% confidence interval [CI]: 1.6 to 2.5; p <0.001) and high ABI (RR:
      1.6; 95% CI: 1.0 to 2.3; p = 0.03). Results were similar when CKD was defined by
      creatinine. CONCLUSIONS: CKD is associated with both the high and the low
      extremes of ABI in community-living older people. Future studies should evaluate
      whether arterial stiffness is an important mechanism leading to CVD in people
      with CKD.

PMID- 19761942
TI  - Bidirectional ventricular tachycardia.

PMID- 19761943
TI  - May active myocarditis mimick arrhythmogenic right ventricular cardiomyopathy
      phenotype by electroanatomic mapping?

PMID- 19761945
TI  - Pulmonary hypertension in heart failure with preserved ejection fraction any
      pathophysiological role of mitral regurgitation.

PMID- 19761946
TI  - Renal protective effects and prevention of contrast-induced nephropathy by atrial
      natriuretic peptide can it work?

PMID- 19761949
TI  - ACC 2009 survey results and recommendations: Addressing the cardiology workforce
      crisis A report of the ACC board of trustees workforce task force.

PMID- 19761951
TI  - Benefits of combining massage therapy with group interpersonal psychotherapy in
      prenatally depressed women.
AB  - One hundred and twelve pregnant women who were diagnosed depressed were randomly
      assigned to a group who received group Interpersonal Psychotherapy or to a group
      who received both group Interpersonal Psychotherapy and massage therapy. The
      group Interpersonal Psychotherapy (1h sessions) and massage therapy (20 min
      sessions) were held once per week for 6 weeks. The data suggested that the group
      who received psychotherapy plus massage attended more sessions on average, and a
      greater percentage of that group completed the 6-week program. The group who
      received both therapies also showed a greater decrease in depression, depressed
      affect and somatic-vegetative symptom scores on the Center for Epidemiological
      Studies-Depression Scale (CES-D), a greater decrease in anxiety scale (STAI)
      scores and a greater decrease in cortisol levels. The group therapy process
      appeared to be effective for both groups as suggested by the increased expression
      of both positive and negative affect and relatedness during the group therapy
      sessions. Thus, the data highlight the effectiveness of group Interpersonal
      Psychotherapy and particularly when combined with massage therapy for reducing
      prenatal depression.

PMID- 19761952
TI  - The migratory fascia hypothesis.
AB  - When treating pelvic obliquity, the author has noticed apparent ridging of soft
      issue in the gluteal region. In an effort to understand this phenomenon, an
      informal field study involved searching athletes for common movement patterns
      that might induce pelvic distortion, including torsion around the vertical axis.
      The author was curious about consequent fascial involvement and its influence on
      lower back pain. The author respectfully reports a subjective palpatory
      observation; a thin palpable fibrous element of superficial fascia presumed to
      work similarly to a trouser belt. This apparently lies parallel and medially deep
      to the iliac crest, extending from the lumbosacral junction laterally, passing
      the antero-superior aspect of the PSIS, then continuing medio-laterally to merge
      with the upper portion of the inguinal ligament. It is suggested that injury
      related displacement of this element, and the adjacent superficial fascia
      laterally across the iliac crest, resulting from sacrificial damage to crural
      elements in the inguinal area, could produce fascial strain patterns,
      contributing to iliolumbar pain symptoms. Displacement, or migration, of fascia
      in this manner is suggested by the author to result in a fascial fold aligned
      with the ASIS and PSIS landmarks, where aponeurotic reinforcement may arrest
      further caudal displacement of fascia. The appearance of the fold varies with the
      amount of relinquished inguinal tension, the thickness of the folded tissue, and
      with the extent of fascial migration. For example, a migration across the entire
      crest may result in a fold that directly bridges about 80% of the ASIS-PSIS axis,
      flattening out at the ends. The correct relocation of the fascia over
      appropriately aligned pelvic bones may then result in the disappearance of the
      fold, which can measure up to 20mm midway. The intention of this paper is to
      encourage more collaborative efforts between clinicians and scientists to further
      understand this apparent phenomenon, and its possible implications for lumbo
      pelvic function. Although a review of anatomy atlases has failed to reveal
      mention of migratory fascia, the author respectfully suggests that dissection,
      specifically aimed at this task, may demonstrate its presence. It is also
      suggested that a retrospective review of lumbo-pelvic MRI records be initiated to
      identify the presence of this proposed fascial feature in the general population.
      Finally, magnetic resonance elastography may be useful in defining areas of
      increased muscular tension, in order to test the migratory fascia hypothesis.

PMID- 19761953
TI  - Performing arts medicine - instrumentalist musicians part I - general
      considerations.
AB  - Performing arts medicine is a relatively new specialty addressing the medical
      needs of dancers, musicians, ice skaters, and gymnasts. This paper focuses on the
      role of healthcare providers in the diagnosis and therapeutic management of
      instrumentalist musicians. Musicians are at high risk for developing painful
      musculoskeletal problems, including pain and overuse injuries, entrapment and
      peripheral neuropathies, and focal dystonias. Musicians' careers are threatened,
      when they are no longer able to play their instrument because of pain and
      dysfunction. To appreciate music-related injuries, it is important that
      clinicians are familiar with the context of musicians' injuries and disorders.
      This is the first paper in a series of three. This paper discusses the importance
      of taking an extended history. The typical history procedures need to be
      broadened when interviewing musicians, and should include instrument-specific
      questions, and questions regarding practice habits, education, repertoire, and
      employment. The second article addresses the physical examination, while the
      third article provides three case reports of musicians with hand problems, which
      serve to illustrate the points made in the first two articles. The articles are
      illustrated with several tables and photographs of musicians to assist the reader
      in assessing instrumentalist musicians and determining the most appropriate
      course of action.

PMID- 19761954
TI  - Effects of the myofascial release in diffuse systemic sclerosis.
AB  - OBJECTIVE: To improve breathing and functionality of the temporomandibular joint
      (TMJ) and hands, by increasing the range of motion (ROM), and to reduce the level
      of pain. METHOD: Twenty myofascial release (MR) sessions in 2002 with assessments
      (chest expansion, mouth opening, ROM of wrist and fingers). Between the 19th and
      the 20th session there was a break of 110 days. Every winter, 1-3 sessions have
      been made. RESULTS: Chest: expansion increased by 3.5 cm and pain was eliminated
      at the scar from a biopsy; TMJ: an 8mm increase in mouth opening with pain
      eliminated; hands and fingers: increase of ROM in all joints of fingers and
      wrists, of up to 100%, reduction in ulcerations and recovery of nail growth.
      CONCLUSION: The connective tissue affected by diffuse systemic sclerosis (dSSc)
      is subject to remodeling through MR, receding when the work is interrupted.
      Resuming the treatment on a regular basis increased the ROM in joints, reduced
      the effects of the Raynaud Phenomenon and the pain.

PMID- 19761955
TI  - Interdisciplinary palliative care, including massage, in treatment of amyotrophic
      lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive fatal neurological disease
      that affects approximately 20,000 Americans. Symptoms include muscle weakness,
      fatigue, twitching, atrophy, spasticity, pain, oropharyngeal dysfunction,
      pseudobulbar affect, weight loss, and respiratory impairment. Death occurs within
      3-5 yr after onset of symptoms, with diagnosis taking from 11 to 17.5 months. The
      only FDA-approved drug for ALS is Riluzole, which only increases the life
      expectancy by a few months. All other treatments for ALS provide symptom
      management to improve the patient's quality of life. An interdisciplinary
      palliative care team for the ALS patient helps to reduce the stress that the
      illness places on families. Massage can be a useful adjunctive treatment for
      spasticity and pain when medication side effects are unwanted. A holistic
      interdisciplinary palliative care team supports both the patient and the family
      improving their quality of life.

PMID- 19761957
TI  - Acute clinical benefits of chest wall-stretching exercise on expired tidal
      volume, dyspnea and chest expansion in a patient with chronic obstructive
      pulmonary disease: a single case study.
AB  - Chest physical therapy (CPT) has an important role in a medical team to assist in
      resolving the critical problems deriving from chronic lung disease. These
      critical problems include increased secretion volume, difficult breathing or
      dyspnea, ineffective coughing, inability to be weaned off a ventilator, and
      physical deterioration resulting from low aerobic capacity and endurance after
      prolonged bed rest. The inability to be weaned off a ventilator does not only
      result from secretion production or muscle weakness, but other conditions
      including chest stiffness or immobility. The procedure to increase chest mobility
      includes specific chest stretching and mobilization. Chest wall-stretching
      exercises were composed of thoracic rotation and anterior compression with
      stretching in sitting position, trunk extension and rib torsion in supine lying,
      and lateral stretching in side lying. These exercises were given to the patient
      as a regular daily program along with postural drainage, percussion, breathing
      exercise and limb exercises. The expired tidal volume, dyspnea level, and chest
      expansion were evaluated and clinical efficiency was analyzed during CPT,
      compared to Pre-CPT and Post-CPT with Bloom table. The results showed a
      significant clinical improvement of expired tidal volume, reduction in dyspnea
      level, and increase in chest expansion.

PMID- 19761958
TI  - Identification of viscoelastic parameters of skin with a scar in vivo, influence
      of soft tissue technique on changes of skin parameters.
AB  - The goal of the experiment was to develop an identification method capable of
      objective detection of changes of viscoelastic properties of skin with a scar
      remaining after a modified radical mastectomy. We compared the intact skin and
      the skin with a scar, a scar before and after physiotherapy. We used two methods.
      The first one is based on measurements of the local dynamic deformation response
      of the skin and the second one is the matrix identification of static deformation
      that identifies properties of the whole tested region of the explored tissues. We
      identified the skin stretchability, shiftability against deeper layers and deeply
      analysed both the methods. In some patients, we found statistically proven
      difference. In all these cases the measurement methods have detected changes of
      the observed tissue condition. We found both methods to be potentially applicable
      after further improvements as a diagnostic tool, which can contribute to the
      improvement of postoperative care of patients.

PMID- 19761959
TI  - The neutral spine principle.

PMID- 19761960
TI  - Self-management: patient section. Training for speed.
AB  - Speed is typically considered an inherited trait. While runners are born not
      made, everyone can improve their speed. There are some basic tips and training
      exercises that can improve any athlete or "weekend warrior's" speed. To optimize
      a person's running ability a specific stimulus is needed. This entails re
      programming the muscle firing patterns by creating a new movement engram on a
      subcortical basis. In the young athlete, the nervous system is most plastic, so
      if good habits are programmed early enough in the developmental training of a
      young athlete, they will provide a solid foundation for the future (Balyi et al.,
      2005; Bompa, 1995; Bouchard et al., 1997; Higgs et al., 2008).

PMID- 19761961
TI  - Muscle activity of the upper and lower rectus abdominis during exercises
      performed on and off a Swiss ball.
AB  - This study sought to examine any differences in upper rectus abdominis (URA) and
      lower rectus abdominis (LRA) muscle activity during four abdominal exercises, the
      curl-up, Swiss ball curl-up, Swiss ball jackknife and Swiss ball rollout.
      Fourteen healthy adults (7 males, 7 females, mean age+/-S.D.=21.8+/-3.8 years)
      performed abdominal exercises in a randomised order following maximal voluntary
      isometric contraction. Muscle activity of the URA and LRA was assessed using
      surface electromyography. Results indicated that activity of the URA was
      significantly greater than muscle activity of the LRA for the curl-up, Swiss ball
      curl-up and Swiss ball rollout. LRA muscle activity was greater than URA during
      the jacknife exercise. Muscle activity during the curl-up was significantly lower
      than muscle activity during the other exercises. To conclude, muscle activity was
      greater when exercises were performed on a Swiss ball in comparison to a stable
      surface and LRA muscle activity was maximized during the Swiss ball jacknife.

PMID- 19761962
TI  - Plastic, reconstructive and aesthetic surgeon: impact of managing perceptions on
      aesthetic publications.

PMID- 19761963
TI  - A 'cure' for the current recdepression.

PMID- 19761964
TI  - [Body composition in maintenance dialysis patients].
AB  - The analysis of the body composition is of great importance in the follow-up of
      the dialysed patients, in order to evaluate the evolution of their nutritional
      state while taking account of their state of hydration. The problems are
      summarized by modifications of the various compartments in particular of the
      muscular mass, associated variations of the state of hydration, calling into
      question the constant ratios usually used, represented by a hydration of the lean
      body mass with 0,732, and a body hydration with 58%. The association of two
      independent techniques, or more, allowing measurements and the estimates of the
      various compartments (the hydration; fatty mass; mineral contents; the lean body
      mass) is the only way of obtaining results easy to interpret and reliable.

PMID- 19761965
TI  - [How valid are food surveys run by dieticians?].
AB  - International recommendations for dialysis treatment include food surveys among
      the necessary tools for nutritional status evaluation. Several methods are used:
      24-hour food recall, 7-day food diary, 3-day food record, food frequency
      questionnaire, and the most innovative, pictures of the ingested food shot and
      sent to the dietician with a mobile phone. The information from these surveys is
      run on software that calculates the amount of ingested nutriments. All these
      methods have their own advantages and drawbacks. Underestimation of energy intake
      by the EA is frequent when compared to other techniques. Protein intake from EA
      can be compared to the proteic catabolic rate (PCR) from urea kinetic modeling.
      Among EA techniques, the 7-day diary provides the best correlation of protein
      intake measured with PCR. It is important that the dietician is adequately
      trained in one of the EA techniques that he or she will be able to apply for the
      longitudinal follow-up of the patients.

PMID- 19761966
TI  - [Assessment and follow-up of nutritional status in hemodialysis patients].
AB  - Malnutrition is common among hemodialysis patients and is associated with
      increased risk of morbidity and mortality. Early recognition and treatment of
      malnutrition is essential to improve the outcome of these patients. Nutritional
      status may be assessed by several clinical markers including dietary records,
      anthropometric measurements and subjective global assessment. Among biochemical
      parameters, albumin is the most commonly used and prealbumin the most useful.
      Protein catabolic rate reflects dietary protein intake. Body composition analysis
      by bioelectrical impedance analysis or better by dual energy X-ray absorptiometry
      offers a reasonable estimation of body compartments such as total body water, fat
      mass and lean body mass. Periodic assessment of nutritional status must take into
      account the limitations of each criteria used.

PMID- 19761967
TI  - [How to estimate the dietary protein intake of a hemodialysis patient? What
      formulate to use in practice?].
AB  - Bed-side formulae established from urea kinetic modelling offers a simple and
      convenient tool to determine the protein catabolic rate (PCR) and its equivalent
      the dietary protein intake (DPI), in hemodialysis patients, two major parameters
      used for assessing the dialysis dose adequacy and its protein nutritional
      consequences. Simplified urea kinetic analysis, must be part of the permanent
      quality control of the hemodialysis patient. These formulae contribute to judge
      more objectively the efficacy of renal replacement therapy program delivered to
      hemodialysis patients. Indeed, these formulae may not substitute to the clinical
      judgment of physician and may not replace conventional and major dialysis
      adequacy indicators (blood pressure control, extracellular and blood pressure
      control, bone and mineral metabolism control, anemia correction) or nutritional
      status (anthropometric data, somatic proteins, subjective global assessment...)
      By providing a way of assessing "dose of dialysis delivered" and "dietary protein
      intake", bed-side formulae derived from urea kinetic modelling offer a convenient
      and cheap means of quantifying dialysis adequacy. These formulae bring to the
      Physician a necessary although not sufficient complementary tool for assessing
      dialysis adequacy in hemodialysis patient.

PMID- 19761968
TI  - [Can the hemodialysis strategy influence the nutritional status of hemodialysis
      patients?].
AB  - Malnutrition is frequent in hemodialysis (HD) patients. The HEMO study has shown
      a progressive decline of nutritional markers, such as body weight, albuminemia
      and protein intake, in prevalent hemodialysis patients during a 3-year follow-up.
      In incident dialysis patients, nutritional status usually improves during the
      first year of HD treatment. Opposite to the HEMO findings, we have shown that
      nutritional stability was achieved during a 5 year follow-up with sequential long
      hour dialysis (3 x 6-8 hours/week). Energy and protein intakes are related to the
      dialysis dose. Moreover, several studies show the nutritional consequences of
      changing the dialysis prescriptions. The switch from conventional HD to short
      daily dialysis improves significantly protein and energy intake and albuminemia.
      Also, increasing treatment time increases significantly the body weight after
      several months. One of the hypothesis for this effect is that uremia-related
      middle molecules compromise the patient appetite. Increasing dialysis time or
      frequency may decrease the level or the time of exposition to these molecules.
      However, the beneficial effect of hemodiafiltration on HD patients' nutritional
      status is not spectacular. Another hypothesis is the role of extra-cellular fluid
      excess and its relationship with inflammation that is deleterious for nutrition.
      In conclusion, dialysis adequacy is a mandatory prerequisite when facing a
      malnourished HD patient. Increasing time or frequency must be part of the
      therapeutic thought in such situation.

PMID- 19761969
TI  - [Daily protein intake 1,2--is that the panacea?].
AB  - Protein malnutrition is regarded as a risk factor of survival of hemodialysis
      patients. That's why good practice guidelines recommend a daily protein intake of
      1.1 - 1.2 g/ (kg x day) irrespective of the gender and the age of patients [9].
      The investigations presented here using urea kinetic modelling exhibit
      significant differences in protein catabolic rate (PCR) in gender and age of the
      patients as far as PCR is related to (kg body weight x day). The difference in
      gender disappears when PCR is related to kg lean body mass x day. From these
      findings it is recommended to relate PCR to lean body weight instead of body
      weight. Also the age of the patients should be taken into consideration.

PMID- 19761970
TI  - [Obesity in haemodialysis: the paradox].
AB  - Overweight, as well as obesity have become mass phenomena with an ever increasing
      prevalence in most countries all over the world, and are associated with a
      greater cardiovascular risk and mortality. Weight excess is usually directly
      related to an additional risk of morbidity and mortality in the general
      population. In contrast, in patients with end-stage renal disease (ESDR) under
      haemodialysis a paradox has been reported, showing that an increased body mass
      index (BMI) was associated with better survival, and vice versa. This paradox
      relationship, sometimes referred to as "reverse epidemiology" proved to be
      relatively constant in chronic haemodialysis and to a lesser extent in peritoneal
      dialysis. Reverse epidemiology is also found in haemodialysis patients for other
      risk factors, such hypertension, or hypercholesterolaemia. And, likewise, this
      phenomenon is also observed in other populations of heavy chronic disease
      suggesting a potential selection bias, such as a real survival benefit for
      obesity in case of the presence of another heavy chronic disease. The possible
      causes and mechanisms of reverse epidemiology are reviewed in this article.

PMID- 19761971
TI  - [Insulin resistance and inflammation in chronic kidney diseases].
AB  - Insulin resistance (IR) and inflammation are now identified as common features in
      chronic kidney disease (CKD) patients. These metabolic abnormalities are both
      predictors of adverse cardiovascular (CV) outcome and are associated with worst
      nutritional status. Unequivocal experimental, epidemiological and clinical
      evidence produced during the past decade causally links inflammation to the
      development of metabolic syndrome or the complications that emerge from these
      pathologies particularly in the context of obesity or type II diabetes patients.
      These observations lead to the hypothesis of "meta-inflammation" : metabolically
      triggered inflammation, with a key role played by adipose tissue. In CKD
      patients, many other factors related with uremia can be causative but the
      abnormal cytokine and adipokine concentrations and the cluster of metabolic
      abnormalities push us to think like other metabolic diseases, that adipose tissue
      dysfunction may be among the pathways that induce inflammation and IR.
      Therapeutic approaches of traditional CV risk factors have been inconclusive or
      failed to improve the outcome of these patients. Further studies assessing the
      impact of renal failure on adipose tissue function and the pathways that are
      altered in this disease may allow to have therapeutic approaches targetting
      adipose tissue dysfunction or inflammation.

PMID- 19761972
TI  - [Erythropoietin: from the receptor to erythropoiesis stimulating agents].

PMID- 19761973
TI  - [Why must the hemoglobin rate be corrected?].

PMID- 19761974
TI  - [Hemoglobin rate and cardiovascular risk].

PMID- 19761975
TI  - [Hemoglobin stability: results of clinical trials].

PMID- 19761976
TI  - Getting a handle on the media: where should we focus our efforts?

PMID- 19761977
TI  - Obesity prevention and control: from clinical tools to public health strategies.

PMID- 19761978
TI  - Not just for kids: new paradigms for vaccine delivery in pediatrics.

PMID- 19761979
TI  - Charting growth.

PMID- 19761980
TI  - Evaluation of left atrial degeneration for the prediction of atrial fibrillation:
      usefulness of integrated backscatter transesophageal echocardiography.
AB  - OBJECTIVES: The purpose of this study was to elucidate the usefulness of
      integrated backscatter (IBS) transesophageal echocardiography (TEE) for the
      evaluation of atrial degeneration and clarify whether atrial degeneration
      predicts the occurrence of atrial fibrillation (AF). BACKGROUND: One of the
      causes of AF is pathological degeneration of the left atrium (LA). However, there
      is no appropriate method to evaluate degeneration of the LA in the clinical
      setting. METHODS: The IBS images were acquired with TEE with a 4- to 7-MHz
      transducer. The IBS values were calculated as the average power of the
      backscattered signal from regions of interest (ROI). In the pathological study,
      we measured IBS values of 21 left atrial specimens obtained from 10 autopsied
      hearts. Relative interstitial area in the ROI was automatically calculated by a
      personal computer. In the clinical study, we measured IBS values of the entire LA
      wall at 5-mm intervals (except the posterior wall) in 42 patients (18 non-AF
      patients, 14 paroxysmal AF patients, and 10 chronic AF patients). Each IBS value
      was color-coded to construct 3-dimensional maps. RESULTS: There was a weak
      correlation between the relative interstitial area and IBS values (r = 0.45, p =
      0.038). Average corrected IBS values of total voxels in color-coded maps in the
      AF group (24.4 +/- 6.4 dB) and the paroxysmal AF group (23.9 +/- 9.6 dB) were
      significantly greater than those in the non-AF group (15.6 +/- 7.4 dB, p =
      0.007), whereas there was no significant difference in LA diameter between the
      paroxysmal AF group (39.4 +/- 6.5 mm) and the non-AF group (36.7 +/- 5.5 mm).
      CONCLUSIONS: With IBS-TEE, we can identify an increase in atrial degeneration
      that might predict the occurrence of AF before LA dilation.

PMID- 19761981
TI  - Safety of contrast agent use during stress echocardiography: a 4-year experience
      from a single-center cohort study of 26,774 patients.
AB  - OBJECTIVES: We evaluated the short- and long-term safety of contrast agents
      during stress echocardiography (SE). BACKGROUND: Concerns about contrast agent
      safety led to revised recommendations for product use in the U.S. METHODS: We
      studied 26,774 patients who underwent SE between November 1, 2003, and December
      31, 2007. The 10,792 patients who comprised the contrast cohort received second
      generation perfluorocarbon-based agents for left ventricular opacification during
      SE. The noncontrast cohort comprised 15,982 patients who had their first SE in
      the same period but without contrast agents. Short-term (< or = 72 h and < or =
      30 days) and long-term (up to 4.5 years) end points were death and myocardial
      infarction (MI). Cox regression models were used. Immediate contrast agent
      related adverse effects were also reported. RESULTS: The contrast cohort had
      older patients (mean [SD] age, 65.8 [12.1] years vs. 62.6 [14.1] years; p <
      0.001), a higher percentage of males (57.4% vs. 52.8%, p < 0.001), and higher
      risk patients compared with the noncontrast cohort. In addition, dobutamine SE
      patients had greater cardiac risk than exercise SE patients. Abnormal SE findings
      in patients who received contrast agents were more frequent (32.4% vs. 27.9%, p <
      0.001). The 2 cohorts had no statistical difference in the incidence of short
      term events (death and MI). Within 72 h, 1 patient in the contrast cohort and 2
      patients in the noncontrast cohort died (p = 0.54); 3 in the contrast cohort and
      7 in the noncontrast cohort had MI (p = 0.92). Within 30 days, 37 patients
      (0.34%) in the contrast cohort and 57 patients (0.36%) in the noncontrast cohort
      died (p = 0.85); 17 patients (0.16%) in the contrast cohort and 16 patients
      (0.10%) in the noncontrast cohort had MI (p = 0.19). Adjusted hazard ratios were
      not different between cohorts for death (0.99; 95% confidence interval: 0.88 to
      1.11) or MI (0.99; 95% confidence interval: 0.80 to 1.22). CONCLUSIONS: The use
      of contrast agents during SE was not associated with an increased short-term or
      long-term risk of death or MI.

PMID- 19761982
TI  - Ultrasound contrast agent safety: from anecdote to evidence.

PMID- 19761983
TI  - Increasing benefit from revascularization is associated with increasing amounts
      of myocardial hibernation: a substudy of the PARR-2 trial.
AB  - OBJECTIVES: We sought to determine: 1) whether F-18-fluorodeoxyglucose (FDG)
      positron emission tomography (PET) parameters identify high-risk patients who
      gain benefit from revascularization; 2) whether there is a cut point for such
      benefit; and 3) predictors of outcome in patients with severe left ventricular
      (LV) dysfunction due to coronary artery disease. BACKGROUND: Patients with
      ischemic LV dysfunction might benefit from revascularization but not without
      risk. The FDG PET imaging can detect viable myocardium that recovers after
      revascularization. In the PARR-2 (PET and Recovery Following Revascularization-2)
      trial, FDG PET imaging showed a nonsignificant trend for improved outcome
      compared with standard care. Understanding the predictors of outcome from this
      prospective trial should help better identify patients at risk and which patients
      most benefit from revascularization. METHODS: This post hoc analysis included 182
      patients with left ventricular ejection fraction (LVEF) <35% and coronary artery
      disease, being considered for revascularization work-up, and randomized to the
      PET arm of PARR-2. The primary outcome was a composite of cardiac death,
      myocardial infarction, or cardiac repeat hospital stay at 1 year. RESULTS: There
      is an interaction between PET mismatch and protocol revascularization such that
      higher mismatch, when combined with revascularization, yields fewer primary
      outcome events (p = 0.02). On the basis of adjusted Cox modeling, with reduced
      mismatch (<7%), the risk is not significantly different with or without
      revascularization. As mismatch increases above this mark, risk is reduced with
      revascularization. Increasing creatinine (for a 10-mumol/l increase: hazard
      ratio: 1.03, 95% confidence interval: 1.01 to 1.06, p = 0.010) is also associated
      with increased risk, whereas decreasing LVEF (for a 2% decrease: hazard ratio:
      1.08, 95% confidence interval: 0.99 to 1.18, p = 0.087) trends toward an
      association with increased risk. CONCLUSIONS: In this post hoc analysis, patients
      with ischemic cardiomyopathy with larger amounts of mismatch have improved
      outcome with revascularization. Renal function was also an independent predictor
      of outcome. The FDG PET seems to define high-risk patients that gain benefit from
      revascularization. (PET and Recovery Following Revascularization [PARR 2];
      NCT00385242).

PMID- 19761984
TI  - Viable: yes, no, or somewhere in the middle?

PMID- 19761985
TI  - Early assessment of myocardial viability by the use of delayed enhancement
      computed tomography after primary percutaneous coronary intervention.
AB  - OBJECTIVES: We sought to explore the relationship between established parameters
      of reperfusion and the extent of myocardial damage measured by the delayed
      enhancement (DE) of iodinated contrast by multidetector computed tomography
      (MDCT) immediately after primary percutaneous coronary intervention (PCI).
      BACKGROUND: Early detection of myocardial viability should be valuable for risk
      stratification of patients with reperfused acute myocardial infarction (AMI).
      METHODS: Consecutive patients without a history of previous AMI who underwent
      primary PCI for an ST-segment elevation AMI were examined by DE-MDCT without an
      additional contrast injection immediately after completion of PCI. No medication
      was administrated to lower the heart rate. Dose modulation lead to an approximate
      mean radiation dose of 5.5 mSv. RESULTS: Thirty patients constituted the study
      population. Mean age was 61.4 +/- 15.6 years, 24 (80%) were men, and 4 (13%) were
      diabetic. Although post-procedural Thrombolysis In Myocardial Infarction (TIMI)
      flow grade 3 was achieved in all patients, DE was detected in 14 (47%) patients.
      Age, sex, hypertension, diabetes, smoking history, serum creatinine levels, and
      pain duration were not associated with the presence of DE. Door-to-balloon time
      (DE 70.3 +/- 33.6 min vs. non-DE 98.3 +/- 70.7 min, p = 0.19) and lesion crossing
      time (DE 18.6 +/- 11.4 min vs. non-DE 16.4 +/- 9.6 min, p = 0.58) did not differ
      between groups. The TIMI myocardial perfusion grade (0 to 1 vs. 2 to 3) after
      stent implantation and electrocardiogram ST-segment resolution (<50% or >/=50%)
      were associated with the presence of DE (p = 0.001 and p = 0.02, respectively).
      Pre-discharge left ventricular ejection fraction was lower in DE than in non-DE
      patients (44.6 +/- 12.4% vs. 54.1 +/- 10.3%, respectively, p = 0.05).
      Hospitalization days (DE 5.6 +/- 3.8 vs. non-DE 4.8 +/- 1.0, p = 0.41) and 6
      month cardiac events (DE 3 of 14 vs. non-DE 1 of 16, p = 0.22) did not differ
      between groups. CONCLUSIONS: Early detection of myocardial viability immediately
      after primary PCI by the use of DE-MDCT is related to clinical and angiographic
      parameters of myocardial reperfusion.

PMID- 19761986
TI  - Rediscovery of infarct imaging by cardiac CT.

PMID- 19761987
TI  - Identification of unexpected nonatherosclerotic cardiovascular disease with
      coronary CT angiography.
AB  - OBJECTIVES: The aim of this study was to assess, in a general cardiology cohort
      screened for obstructive coronary artery disease (CAD), the effectiveness and
      frequency with which multidetector computed tomography (MDCT) angiography
      unexpectedly imaged and identified other nonatherosclerotic cardiovascular
      diseases. BACKGROUND: MDCT angiography is a novel imaging strategy employed
      primarily to diagnose CAD that, in the course of these studies, can also
      potentially identify other important but previously unrecognized cardiovascular
      abnormalities. METHODS: Consecutive 64-slice MDCT angiography studies were
      obtained in 4,543 patients with suspected atherosclerotic CAD at the Minneapolis
      Heart Institute, over a 29-month period (2005 to 2007). RESULTS:
      Nonatherosclerotic-related cardiovascular abnormalities judged to be of potential
      clinical relevance were identified in 201 patients (4.4%). In 50 of these
      patients (1.1% of 4,543) the abnormality was previously unrecognized despite
      other imaging studies performed in 40%. Most common among the 50 patients were:
      congenital coronary artery anomalies (38%; largely right coronary artery from the
      left aortic sinus); ascending aortic aneurysms > or = 45 mm (22%); hypertrophic
      cardiomyopathy with apical left ventricular (LV) wall thickening (14%); valvular
      heart diseases (8%), congenital heart diseases, including ventricular septal
      defect (6%); pulmonary embolus (6%); as well as LV noncompaction, left atrial
      myxoma, and LV apical aneurysm (2% each). As a consequence of MDCT angiography
      findings, new management strategies were instituted in 15 of 50 patients (30%),
      including surgical correction of coronary artery anomalies of wrong sinus origin,
      ascending aneurysm graft repair, thrombolytic therapy for pulmonary embolism, and
      myxoma resection. CONCLUSIONS: Approximately 1% of patients undergoing MDCT
      angiography for suspicion of CAD proved to have otherwise unsuspected, but
      clinically relevant, cardiovascular abnormalities unrelated to coronary
      atherosclerosis. Almost one-third of these patients had cardiovascular diseases
      with major clinical implications for subsequent therapy. These findings
      underscore the value of MDCT angiography and the importance of careful assessment
      of scans for the recognition of a variety of cardiovascular abnormalities.

PMID- 19761988
TI  - Myeloperoxidase, subclinical atherosclerosis, and cardiovascular disease events.
AB  - OBJECTIVES: We evaluated whether myeloperoxidase (MPO) predicts future
      cardiovascular disease (CVD) events in asymptomatic adults and whether
      subclinical atherosclerosis may affect this relation. BACKGROUND: Myeloperoxidase
      is a leukocyte-derived enzyme-generating reactive oxidant species that has been
      shown to predict risk of CVD in selected populations. METHODS: We studied 1,302
      asymptomatic adults (mean age 59 years, 47% women) without known CVD who were
      followed for 3.8 years. We measured MPO by the use of immunoassay. Coronary
      artery calcium (CAC), a measure of subclinical atherosclerosis, was measured by
      computed tomography with the Agatston score categorized as none/minimal (0 to 9),
      mild (10 to 99), and moderate/significant (> or = 100). Cox regression, adjusted
      for age, sex, and other risk factors, examined the relation of CAC and/or MPO
      with incident CVD events. RESULTS: Persons with MPO levels at or above compared
      with below the median (257 pM) were more likely (p < 0.05 to p < 0.001) to be
      women, have a higher body mass index, greater low-density lipoprotein
      cholesterol, greater systolic and diastolic blood pressure, and lower high
      density lipoprotein cholesterol. Mean MPO levels increased according to CAC
      categories (p trend = 0.02). Incident CVD events were more likely in those at or
      above versus below the median MPO level (4.6% vs. 2.3%, p = 0.02), even after
      adjustment for age, sex, CAC, and risk factors (hazard ratio [HR]: 1.9, 95%
      confidence interval: 1.0 to 3.6, p = 0.04). Combining CAC and MPO categories, CVD
      incidence ranged from 0.6% in those with a CAC score of 0 to 9 to 7.1% (adjusted
      HR: 9.2, p < 0.001) in those with CAC scores of > or = 100 and MPO below the
      median and 14.0% (adjusted HR: 19.5, p < 0.0001) in those with CAC scores of > or
      = 100 and MPO at or above the median. CONCLUSIONS: Our study suggests persons
      with both increased levels of both MPO and CAC are at an increased risk of CVD
      events. Imaging of subclinical atherosclerosis combined with assessment of
      biomarkers of plaque vulnerability may help improve CVD risk stratification.

PMID- 19761989
TI  - Enhancing the prognostic value of cardiac imaging with multimodal risk
      assessment.

PMID- 19761990
TI  - Accuracy of cardiac magnetic resonance of absolute myocardial blood flow with a
      high-field system: comparison with conventional field strength.
AB  - OBJECTIVES: The aim of this study was to determine the accuracy of cardiac
      magnetic resonance (CMR) first pass (FP) perfusion measures of absolute
      myocardial blood flow (MBF) with a 3.0-T magnet and compare these measures with
      FP perfusion at 1.5-T with absolute MBF by labeled microspheres as the gold
      standard. BACKGROUND: First-pass magnetic resonance (MR) myocardial perfusion
      imaging can quantify MBF, but images are of low signal at conventional magnetic
      field strength due to the need for rapid acquisition. METHODS: A pig model was
      used to alter MBF in a coronary artery during FP CMR (intracoronary adenosine
      followed by ischemia). This produces an active zone with a range of MBF and a
      control zone. Microspheres were injected into the left atrium with concurrent
      reference sampling. FP MR perfusion imaging was performed at 1.5-T (n = 9) or 3.0
      T (n = 8) with a saturation-recovery gradient echo sequence in short-axis slices
      during a bolus injection of 0.025 mmol/kg gadolinium-diethylenetriamine
      pentaacetic acid. Fermi function deconvolution was performed on active and
      control region of interest from short-axis slices with an arterial input function
      derived from the left ventricular cavity. These MR values of MBF were matched to
      microsphere values obtained from short-axis slices at pathology. RESULTS:
      Occlusion MBF was 0.21 +/- 0.26 ml/min/g, adenosine MBF was 2.28 +/- 0.99
      ml/min/g, and control zone MBF was 0.70 +/- 0.22 ml/min/g. The correlation of MR
      FP CMR with microsphere was close for both field strengths: 3.0-T, r = 0.98, p <
      0.0001 and 1.5-T, r = 0.95, p < 0.0001. The 95% confidence limits of agreement
      were slightly narrower at 3.0-T (3.0-T = 0.49 ml/min/g, 1.5-T = 0.68 ml/min/g, p
      < 0.05). The FP CMR image characteristics were better at 3.0-T (noise and
      contrast enhancement were both superior at 3.0-T). In myocardial zones where MBF
      <0.50 ml/min/g, the correlation with microspheres was closer at 3.0-T (r = 0.55
      at 1.5-T, r = 0.85 at 3.0-T). CONCLUSIONS: Absolute MBF by FP perfusion imaging
      is accurate at both 1.5- and 3.0-T. Signal quality is better at 3.0-T, which
      might confer a benefit for estimating MBF in ischemic zones.

PMID- 19761991
TI  - Man must measure: except for cardiologists!

PMID- 19761992
TI  - In vivo detection of embryonic stem cell-derived cardiovascular progenitor cells
      using Cy3-labeled Gadofluorine M in murine myocardium.
AB  - OBJECTIVES: The aim of the current study is to test the ability to label and
      detect murine embryonic stem cell-derived cardiovascular progenitor cells (ES
      CPC) with cardiac magnetic resonance (CMR) using the novel contrast agent
      Gadofluorine M-Cy3 (GdFM-Cy3). BACKGROUND: Cell therapy shows great promise for
      the treatment of cardiovascular disease. An important limitation to previous
      clinical studies is the inability to accurately identify transplanted cells. GdFM
      Cy3 is a lipophilic paramagnetic contrast agent that contains a perfluorinated
      side chain and an amphiphilic character that allows for micelle formation in an
      aqueous solution. Previous studies reported that it is easily taken up and stored
      within the cytosol of mesenchymal stem cells, thereby allowing for paramagnetic
      cell labeling. Investigators in our laboratory have recently developed techniques
      for the robust generation of ES-CPC. We reasoned that GdFM-Cy3 would be a
      promising agent for the in vivo detection of these cells after cardiac cell
      transplantation. METHODS: ES-CPC were labeled with GdFM-Cy3 by incubation. In
      vitro studies were performed to assess the impact of GdFM-Cy3 on cell function
      and survival. A total of 500,000 GdFM-Cy3-labeled ES-CPC or control ES-CPC were
      injected into the myocardium of mice with and without myocardial infarction. Mice
      were imaged (9.4-T) before and over a 2-week time interval after stem cell
      transplantation. Mice were then euthanized, and their hearts were sectioned for
      fluorescence microscopy. RESULTS: In vitro studies demonstrated that GdFM-Cy3 was
      easily transfectable, nontoxic, stayed within cells after labeling, and could be
      visualized using CMR and fluorescence microscopy. In vivo studies confirmed the
      efficacy of the agent for the detection of cells transplanted into the hearts of
      mice after myocardial infarction. A correspondence between CMR and histology was
      observed. CONCLUSIONS: The results of the current study suggest that it is
      possible to identify and potentially track GdFM-Cy3-labeled ES-CPC in murine
      infarct models via CMR.

PMID- 19761993
TI  - Magnetic resonance labeling of stem cells: is positive tracking a plus or a
      minus?

PMID- 19761994
TI  - The role of multimodality cardiac imaging in the transplanted heart.
AB  - Heart transplantation (HT) is an established life-saving treatment option for
      patients with end-stage heart failure. Despite many advances in the field, the
      development of acute cellular rejection (ACR) and cardiac allograft vasculopathy
      (CAV) represent significant causes of 1- and 5-year morbidity and mortality,
      respectively. The search for noninvasive techniques to assess cardiac allograft
      function and detect treatable ACR and CAV remains a priority objective for heart
      transplant professionals. In this review we will: 1) highlight the clinical
      significance of ACR and CAV in adult cardiac transplant recipients and 2) discuss
      how different noninvasive imaging modalities (echocardiography, cardiac computed
      tomography, myocardial perfusion imaging, and cardiac magnetic resonance) have
      been used in the evaluation of these clinical challenges after HT.

PMID- 19761995
TI  - Characterization of acute myocardial infarction by magnetic resonance imaging.

PMID- 19761996
TI  - Cardiovascular magnetic resonance imaging: is only one shop worth the stop?

PMID- 19761997
TI  - Pelvic nerve injury following gynecologic surgery: a prospective cohort study.
AB  - OBJECTIVE: The purpose of this study was to determine the incidence and time
      course of postoperative neuropathy resulting from gynecologic surgery. STUDY
      DESIGN: A single cohort of 616 female patients undergoing elective gynecologic
      surgery for benign or malignant conditions at a tertiary care academic medical
      center underwent a postoperative neurologic evaluation to identify postoperative
      neuropathy of the lower extremities. RESULTS: Fourteen peripheral nerve injuries
      were observed in 11 patients, making the overall incidence of postoperative
      neuropathy 1.8% (95% confidence interval, 1.0-3.2). Injury to the lateral femoral
      cutaneous (5), femoral (5), common fibular (1), ilioinguinal/iliohypogastric (1),
      saphenous (1), and genitofemoral (1) nerves were detected. Complete resolution of
      neuropathic symptoms occurred in all but 1 patient (91%). Median time to
      resolution of symptoms was 31.5 days (range, 1 day to 6 months). CONCLUSION: The
      incidence of lower extremity neuropathy attributable to gynecologic operations is
      low, and these neuropathies resolve in the great majority of cases.

PMID- 19761998
TI  - Latency and infectious complications after preterm premature rupture of
      membranes: impact of body mass index.
AB  - OBJECTIVE: Obesity has been associated with chronic inflammation. We hypothesized
      that body mass index may be inversely related to latency and directly related to
      infectious complications after preterm premature rupture of membranes. STUDY
      DESIGN: This secondary analysis of a randomized trial of antibiotics for preterm
      premature rupture of membranes had information available for 562 subjects. We
      analyzed the association between body mass index and latency, the occurrence of
      chorioamnionitis, endometritis, and maternal infectious morbidity after
      controlling for gestational age at rupture and treatment group. Survival
      analysis, regression, and test of proportions were used as appropriate. RESULTS:
      When evaluated as a categorical or continuous variable, body mass index did not
      reveal any significant associations. Latency to delivery was affected by
      gestational age at rupture of membrane and antibiotic therapy but not by body
      mass index group. CONCLUSION: Body mass index was not associated with latency or
      the occurrence of maternal infectious complications during conservative
      management of premature rupture of membranes before 32 weeks' gestation.

PMID- 19761999
TI  - Left upper quadrant laparoscopic placement: effects of insertion angle and body
      mass index on distance to posterior peritoneum by magnetic resonance imaging.
AB  - OBJECTIVE: To determine the ideal angle for insertion of laparoscopic instruments
      at Palmer's point. STUDY DESIGN: Abdominal magnetic resonance images were
      reviewed for 75 women between ages 18 and 50 years old. The distance from the
      skin to the retroperitoneal structures were determined perpendicular to the spine
      and angled 45 degrees caudally. RESULTS: When instruments are inserted
      perpendicular to the skin in the axial plane and peritoneum perpendicular to the
      spine, the distance from skin to posterior was 10.0 +/- 0.2 cm and to the aorta
      was 11.3 +/- 0.2 cm. If instruments are inserted at an angle 45 degrees caudally,
      this distance increased to 16.6 +/- 0.2 cm. CONCLUSION: When inserting
      laparoscopic instruments at Palmer's point, insertion perpendicular to the skin
      in the axial plane and angled 45 degrees caudally in relation to the spine offers
      an increased margin of safety compared with insertion perpendicular to the spine,
      particularly in thin women.

PMID- 19762000
TI  - Medication effects on midtrimester maternal serum screening.
AB  - OBJECTIVE: To determine whether medication classes are associated with
      alterations in concentrations of Quad screen analytes or the screen-positive
      rate. STUDY DESIGN: We conducted a retrospective cohort study of women with
      singleton gestations who received prenatal care and had a Quad screen performed
      in the University of Alabama at Birmingham system. Information on prescription
      medications was abstracted. Mean multiples of the medians for each analyte (alpha
      fetoprotein, estriol, human chorionic gonadotropin, and inhibin A) and overall
      screening results were compared between those taking the class of medication and
      controls not taking any medications. RESULTS: There were 6206 women evaluated;
      1337 took at least 1 prescription medicine and 4869 were controls. Mean analyte
      multiples of the medians were significantly different in women taking some
      medications compared with controls. Women taking certain medications had an
      increased screen-positive rate. CONCLUSION: Medications taken around the time of
      maternal serum screening are associated with alterations in individual analyte
      multiples of the medians, as well as the screen-positive rates.

PMID- 19762001
TI  - Automated assays for sVEGF R1 and PlGF as an aid in the diagnosis of preterm
      preeclampsia: a prospective clinical study.
AB  - OBJECTIVE: The purpose of this study was to assess the utility of soluble
      vascular endothelial growth factor 1 (sVEGF R1) and placental growth factor
      (PlGF) levels in the clinical diagnosis of preeclampsia. STUDY DESIGN: Plasma was
      collected prospectively from 457 subjects (n = 409 without preeclampsia, n = 48
      with preeclampsia) at 20-36 weeks' gestation. Automated immunoassays were used to
      measure free sVEGF R1 and free PlGF. RESULTS: Clinical sensitivities of 0.96 and
      specificities of 0.96 and 0.95 were calculated for sVEGF R1 and PlGF,
      respectively, for aiding in the diagnosis of preeclampsia. Among subjects with
      chronic hypertension, sVEGFR1 was dramatically elevated and PlGF decreased in
      those with superimposed preeclampsia (P < .001 for superimposed preeclampsia vs
      chronic hypertension for both biomarkers). The ratio of sVEGFR1/PlGF provided a
      better test to aid in the diagnosis of preeclampsia than either analyte alone (3%
      false positive rate). CONCLUSION: Free sVEGF R1 and PlGF were useful in
      differentiating women with preterm preeclampsia from normotensive and
      hypertensive subjects.

PMID- 19762002
TI  - Defining an at-risk population for obstetric anal sphincter laceration.
AB  - OBJECTIVE: The purpose of this study was to calculate the number of cesarean
      deliveries needed to prevent 1 case of obstetric anal sphincter laceration
      associated with operative vaginal delivery in an at-risk cohort. STUDY DESIGN: An
      institutional, computerized database was used to analyze women with obstructed
      labor who could have been managed by either operative vaginal or cesarean
      delivery from September 2006 to March 2008. Women with 1 or more of the following
      diagnoses comprised the cohort: cephalopelvic disproportion (CPD), arrest of
      descent, maternal exhaustion, and fetal distress. RESULTS: Fifty (23.9%) out of a
      total of 209 women managed by operative vaginal delivery experienced an anal
      sphincter laceration compared to none of 254 women in the cesarean delivery group
      (P < .0001). The ARR therefore was 23.9% (95% confidence interval, 18.1-29.7) and
      the NNT was 4.2 (95% confidence interval, 3.4-5.5). CONCLUSION: Five cesarean
      deliveries are needed to prevent 1 anal sphincter laceration associated with
      operative vaginal delivery in this cohort.

PMID- 19762003
TI  - Long-term efficacy of the pubovaginal Mersilene mesh sling.
AB  - OBJECTIVE: The objective of the study was to determine the efficacy of the
      pubovaginal Mersilene mesh sling (PVMMS) for complicated urodynamic stress
      incontinence (USI). STUDY DESIGN: Between 1990 and 2008, patients with USI plus
      an at-risk diagnosis underwent a PVMMS by a single surgeon. They were followed up
      with urodynamics (UDE) and Pelvic Floor Distress Inventory-short form 20 (PFDI
      20). Stratification was in an at-risk hierarchy: intrinsic sphincter deficiency
      (ISD) greater than recurrent USI (RUSI) greater than USI with chronically
      increased intraabdominal pressure (CI-IAP). A cough stress test determined
      objective cure. PFDI question 17 assessed subjective cure. RESULTS: Three hundred
      six patients with ISD (43.5%), RUSI (26.8%), and CI-IAP (29.7%) had objective
      cure rates of 89.2% in the short term, 86.7% in the intermediate term, and 91.2%
      in the long term. A group of 48 patients with both short- and long-term UDEs
      showed cures of 100% and 91.7%. Long-term objective cure rates were: ISD, 90.5%
      (n = 21); RUSI, 84.2%, (n = 19); CI-IAP, 100% (n = 17). The mean score of
      postoperative PFDI question 17 was 0.57 (n = 119). Mean symptom improvement was 
      2.98 (n = 52; P < .0001). CONCLUSION: We demonstrated PVMMS to be subjectively
      and objectively effective in long-term treatment of complicated forms of USI.

PMID- 19762004
TI  - Racial disparities in stillbirth risk across gestation in the United States.
AB  - OBJECTIVE: We sought to determine factors associated with racial disparities in
      stillbirth risk. STUDY DESIGN: Stillbirth hazard was analyzed using 5,138,122
      singleton gestations from the National Center of Health Statistics perinatal
      mortality and birth files, 2001-2002. RESULTS: Black women have a 2.2-fold
      increased risk of stillbirth compared with white women. The black/white disparity
      in stillbirth hazard at 20-23 weeks is 2.75, decreasing to 1.57 at 39-40 weeks.
      Higher education reduced the hazard for whites more than for blacks and
      Hispanics. Medical, pregnancy, and labor complications accounted for 30% of the
      hazard in blacks and 20% in whites and Hispanics. Congenital anomalies and small
      for gestational age contributed more to preterm stillbirth risk among whites than
      blacks. Pregnancy and labor conditions contributed more to preterm stillbirth
      risk among blacks than whites. CONCLUSION: The excess stillbirth risk for blacks
      was greatest at preterm gestations, and factors contributing to stillbirth risk
      vary by race and gestational age.

PMID- 19762005
TI  - An ethically justified practical approach to offering, recommending, performing,
      and referring for induced abortion and feticide.
AB  - We provide comprehensive, practical guidance for physicians on when to offer,
      recommend, perform, and refer patients for induced abortion and feticide. We
      precisely define terminology and articulate an ethical framework based on
      respecting the autonomy of the pregnant woman, the fetus as a patient, and the
      individual conscience of the physician. We elucidate autonomy-based and
      beneficence-based obligations and distinguish professional conscience from
      individual conscience. The obstetrician's role should be based primarily on
      professional conscience, which is shaped by autonomy-based and beneficence-based
      obligations of the obstetrician to the pregnant and fetal patients, with
      important but limited constraints originating in individual conscience.

PMID- 19762006
TI  - Optimization of the operating parameters of a grass trimming machine.
AB  - Hand-arm vibration syndrome (HAVS) is very common among the workers operating
      power tools and doing similar nature of work for long hours. Grass trimming is
      one of the operations that involves use of vibrating cutter, and results in hand
      arm vibration among workers. In this study, the influence of several operating
      parameters (length of nylon cutting thread, engine speed and handle material) is
      investigated in terms of HAV. Data are analyzed via orthogonal array, main
      effect, signal-to-noise (S/N) ratio, and analysis of variance to determine the
      appropriate operating parameter levels to minimize HAV. Operating parameters
      under investigation are found to be influential in controlling HAV generation
      during grass trimming operation. Experiments are carried out for measuring hand
      arm vibration using tri-axial accelerometer conforming the effectiveness of this
      approach. Results show that 100mm length of nylon thread, 3000+/-400rpm of engine
      speed and ABS handle material combination results in minimum HAV (HARM) of
      magnitude 2.76m/s(2). Through this study not only the optimal operating parameter
      levels for GTM are obtained, but also the main process parameters that affect the
      HAV are determined. The optimum HAV obtained through appropriate level selection
      of operating parameters, significantly reduces the occurrence of HAVS among the
      grass trimmers.

PMID- 19762007
TI  - Regional differences in blood flow variation in rat masseter muscle.
AB  - Regions of a belly in a masseter muscle have been suggested to be activated
      independently in order to enable complex jaw-movements. However a regional
      difference of the masseter blood flow (MBF) is still unclear although the blood
      flow is one of the most important factors during activation of the muscle. The
      present study examined regional differences in blood flow in rat masseter muscle
      by comparing blood flow values at the inferior, centre, superior, anterior, and
      posterior regions of the muscle belly using a laser speckle imaging flowmeter
      with or without sympathetic and parasympathetic stimulation. Regional differences
      in blood flow levels were observed in each region of the masseter muscle belly
      during rest. Additionally, amplitudes of blood flow changes evoked by electrical
      stimulation of parasympathetic and sympathetic nerves differed among regions.
      These results demonstrate the regional differences in hemodynamics during rest,
      sympathetic vasoconstriction (including the recovery phase), and parasympathetic
      vasodilatation in rat masseter muscle.

PMID- 19762008
TI  - X-ray crystal structure of iridoid glucoside aucubin and its aglycone.
AB  - X-ray diffraction analyses of iridoid glycoside aucubin (1) and its aglycone
      aucubigenin (2) are reported. It was found that crystals of 1 are orthorhombic,
      with P2(1)2(1)2(1) space group, both cyclopentane ring and pyran ring adopt
      envelope conformations, and the Glc moiety is in the (4)C(1) conformation.
      Crystals of 2 are monoclinic, with space group P2(1), the cyclopentane and pyran
      rings also adopt the envelope conformation. The absolute configurations of 1 and
      2 were also determined. Intensive O-H . . . O hydrogen bonds in both crystal
      lattices were observed.

PMID- 19762009
TI  - New cell wall glycopolymers of the representatives of the genus Kribbella.
AB  - Each of the cell walls of four representatives of the genus Kribbella (order
      Actinomycetales; suborder Propionibacterineae; family Nocardioidaceae) contains a
      neutral polysaccharide and an acidic polysaccharide with unusual structures.
      Common to all four strains studied is a mannan with the following repeating unit:
      [structure: see text]. In the cell wall of the strain VKM Ac-2541, a
      teichulosonic acid was identified with a monosaccharide component that has not
      hitherto been found in Gram-positive bacteria, viz., pseudaminic acid, and an
      unusual linkage type in the polymeric chain, [structure: see text] where
      R=capital EN, Cyrillic (45%), alpha-D-Galp3OMe (37%) or alpha-D-Galp2,3OMe (18%).
      The anionic cell wall components of three other strains are represented by
      teichuronic acids with a rare constituent, viz., a diaminosugar, 2,3-diacetamido
      2,3-dideoxyglucopyranose. The structures of their repeating units differ in the
      nature of the acidic components: -->4)-beta-D-Manp2,3NAcA-(1-->6)-alpha-D
      Glcp2,3NAc-(1--> (VKM capital A, Cyrillicsmall es, Cyrillic-2538 and VKM capital
      A, Cyrillicsmall es, Cyrillic-2540) and -->4)-beta-D-ManpNAcA-(1-->6)-alpha-D
      Glcp2,3NAc-(1--> (VKM capital A, Cyrillicsmall es, Cyrillic-2539). The structures
      of all the glycopolymers were established by chemical and NMR spectroscopic
      methods; they are identified in Gram-positive bacteria for the first time.

PMID- 19762010
TI  - Comparative analysis of the Epstein-Barr virus encoded nuclear proteins of EBNA-3
      family.
AB  - It is known that the EBNA-3 family proteins (EBNA-3, -4 and -6, alternative
      nomenclature EBNA-3A, B and C correspondingly) show a limited sequence
      similarity. We have analyzed EBNA-3 proteins both at the primary sequence and
      secondary structure levels. EBNA-3 and EBNA-4 were structurally more similar
      compared to other combinations with EBNA-6. We found "Stonin Homology Domain"
      profile in EBNA-4 and "Proline Rich Domain" in all EBNA-3 family of proteins. We
      have also found positive and negative charge clusters in all three proteins and
      mixed charge clusters in EBNA-3. Charged clusters are believed to play an
      important role in interactions with DNA or signaling proteins. Additionally,
      unique primary sequence repeats were found in all three proteins.

PMID- 19762011
TI  - Detection of ventricular fibrillation using empirical mode decomposition and
      Bayes decision theory.
AB  - Ventricular fibrillation (VF) is the most serious variety of arrhythmia which
      requires quick and accurate detection to save lives. In this paper, we propose an
      empirical mode decomposition (EMD) based algorithm for VF detection. The
      intrinsic mode functions (IMFs) of VF are orthogonal whereas the lower order IMFs
      of normal sinus rhythm (NSR) are not. The orthogonality indices derived from the
      first three consecutive intrinsic mode functions (IMFs) of NSR and VF are used
      for their discrimination. The proposed technique is applied to the MIT-BIH
      arrhythmia database. The accuracy of detection of VF is 99.70% for a window
      length of 3s. This early estimate of VF may be useful in emergency cases where
      defibrillators are to be applied. Comparative results with the existing methods
      in terms of quality parameters and integrated receiver operating characteristic
      (IROC) are presented.

PMID- 19762012
TI  - Energy based feature extraction for classification of sleep apnea syndrome.
AB  - In this paper it is aimed to classify sleep apnea syndrome (SAS) by using
      discrete wavelet transforms (DWT) and an artificial neural network (ANN). The
      abdominal and thoracic respiration signals are separated into spectral components
      by using multi-resolution DWT. Then the energy of these spectral components are
      applied to the inputs of the ANN. The neural network was configured to give three
      outputs to classify the SAS situation of the subject. The apnea can be mainly
      classified into three types: obstructive sleep apnea (OSA), central sleep apnea
      (CSA) and mixed sleep apnea (MSA). During OSA, the airway is blocked while
      respiratory efforts continue. During CSA the airway is open, however, there are
      no respiratory efforts. In this paper we aim to classify sleep apnea in one of
      three basic types: obstructive, central and mixed. A significant result was
      obtained.

PMID- 19762013
TI  - Contribution of frontal cortex to the spatial representation of number.
AB  - Neuropsychological and neurophysiological studies have suggested that prefrontal
      cortex may be involved in non-verbal number processing, when relevant for current
      behavioural goals. More precisely, it has been suggested that an intact right
      inferior frontal gyrus (rIFG) in humans may be necessary to the use of a spatial
      representation of numbers, also known as mental number line. In a popular model
      of spatial functions (e.g., Corbetta et al., 2008), rIFG is part of a right
      lateralised ventral fronto-parietal network that conveys signals to a dorsal
      network supporting attentional orienting in contralateral space. Within the
      dorsal network, the frontal eye fields (FEF) are known to contribute to visual
      scene analysis and visual conjunction search tasks when eye movement commands are
      not required. In the present study, we hypothesised they might also be involved
      in exploring a conceptual space, such as the mental number line. We examined the
      proposed functions of the human rIFG and right Frontal Eye Field (rFEF) by
      interfering with their normal functioning with repetitive Transcranial Magnetic
      Stimulation (rTMS) while participants performed numerical tasks. The results
      suggest that, when number magnitude is relevant to the task, rIFG supports
      orienting to the entire mental number line while rFEF are crucial for
      contralateral orienting (that is towards small numbers).

PMID- 19762014
TI  - Complexities of holistic community-based participatory research for a low income,
      multi-ethnic population exposed to multiple built-environment stressors in
      Worcester, Massachusetts.
AB  - Low income, multi-ethnic communities in Main South/Piedmont neighborhoods of
      Worcester, Massachusetts are exposed to cumulative, chronic built-environment
      stressors, and have limited capacity to respond, magnifying their vulnerability
      to adverse health outcomes. "Neighborhood STRENGTH", our community-based
      participatory research (CBPR) project, comprised four partners: a youth center;
      an environmental non-profit; a community-based health center; and a university.
      Unlike most CBPR projects that are single topic-focused, our 'holistic', systems
      based project targeted five priorities. The three research-focused/action
      oriented components were: (1) participatory monitoring of indoor and outdoor
      pollution; (2) learning about health needs and concerns of residents through
      community-based listening sessions; (3) engaging in collaborative survey work,
      including a household vulnerability survey and an asthma prevalence survey for
      schoolchildren. The two action-focused/research-informed components were: (4)
      tackling persistent street trash and illegal dumping strategically; and (5)
      educating and empowering youth to promote environmental justice. We used a
      coupled CBPR-capacity building approach to design, vulnerability theory to frame,
      and mixed methods: quantitative environmental testing and qualitative surveys.
      Process and outcomes yielded important lessons: vulnerability theory helps frame
      issues holistically; having several topic-based projects yielded useful
      information, but was hard to manage and articulate to the public; access to, and
      engagement with, the target population was very difficult and would have
      benefited greatly from having representative residents who were paid at the
      partners' table. Engagement with residents and conflict burden varied highly
      across components. Notwithstanding, we built enabling capacity, strengthened our
      understanding of vulnerability, and are able to share valuable experiential
      knowledge.

PMID- 19762015
TI  - Influence of litter size on the postnatal growth of rat pups: is there a
      rationale for litter-size standardization in toxicity studies?
AB  - The standardization of rodent litter sizes (or culling) in reproductive toxicity
      studies has become a common practice because it is believed that litter size
      affects pup postnatal growth and development. A claim has also been made that
      culling on postnatal day 4 or earlier reduces litter-size-induced variability in
      the pup growth thereby making statistical detection of toxic effects more
      sensitive. Although these statements remain controversial, culling has been
      either recommended or considered optional in current proposals for new OECD
      guidelines for reproductive/developmental toxicity testing. This study was
      undertaken to provide data useful for a discussion on the need for culling in
      reproductive toxicity testing. Along this line, we investigated the effects of
      rat litter size on maternal body weight gain during pregnancy and lactation as
      well as on pup growth, somatic maturation and survival to weaning (PND 21). Two
      hundred-forty-one untreated pregnant rats (Wistar, Bor:spf, TOR) delivered
      litters with 1-13 pups, being 10 the most frequent (24%) litter size. Pup
      mortality was 5.4%, 3.0% and 0.4% in the first, second and third postnatal weeks,
      respectively. Maternal and pup body weight gains, and the day of appearance of
      milestones of somatic maturation (fur development, incisor eruption and eye
      opening) were examined in a subset of litters/mothers (N=180) in which all pups
      survived to PND 21. An inverse relationship between litter size and pup body
      weight was found on day of birth (PND 1) and thereafter until PND 21. Delays in
      the attainment of maturational milestones as litter size increases were also
      found. These observations indicated that the rate of growth and development of
      rat pups during suckling period is dependent on the litter size. The consequences
      of litter-size standardization in toxicity studies are discussed in the light of
      these findings. Alternative procedures to attenuating litter-size-induced
      variability in pup growth or its impact on toxicity data evaluation are presented
      as well.

PMID- 19762016
TI  - The effect of computer-assisted learning versus conventional teaching methods on
      the acquisition and retention of handwashing theory and skills in pre
      qualification nursing students: a randomised controlled trial.
AB  - BACKGROUND: High quality health care demands a nursing workforce with sound
      clinical skills. However, the clinical competency of newly qualified nurses
      continues to stimulate debate about the adequacy of current methods of clinical
      skills education and emphasises the need for innovative teaching strategies.
      Despite the increasing use of e-learning within nurse education, evidence to
      support its use for clinical skills teaching is limited and inconclusive.
      OBJECTIVES: This study tested whether nursing students could learn and retain the
      theory and skill of handwashing more effectively when taught using computer
      assisted learning compared with conventional face-to-face methods. DESIGN: The
      study employed a two group randomised controlled design. The intervention group
      used an interactive, multimedia, self-directed computer-assisted learning module.
      The control group was taught by an experienced lecturer in a clinical skills
      room. Data were collected over a 5-month period between October 2004 and February
      2005. Knowledge was tested at four time points and handwashing skills were
      assessed twice. SETTING AND PARTICIPANTS: Two-hundred and forty-two first year
      nursing students of mixed gender; age; educational background and first language
      studying at one British university were recruited to the study. Participant
      attrition increased during the study. RESULTS: Knowledge scores increased
      significantly from baseline in both groups and no significant differences were
      detected between the scores of the two groups. Skill performance scores were
      similar in both groups at the 2-week follow-up with significant differences
      emerging at the 8-week follow-up in favour of the intervention group, however,
      this finding must be interpreted with caution in light of sample size and
      attrition rates. CONCLUSION: The computer-assisted learning module was an
      effective strategy for teaching both the theory and practice of handwashing to
      nursing students and in this study was found to be at least as effective as
      conventional face-to-face teaching methods.

PMID- 19762017
TI  - The effects of multisensory therapy on behaviour of adult clients with
      developmental disabilities--a systematic review.
AB  - BACKGROUND: There is a growing use of multisensory therapy in enhancing sense of
      well-being and reducing challenging or stereotypic self-stimulating behaviour in
      people with a developmental disability. OBJECTIVES: This review aimed to present
      the best available evidence on the effect of multisensory therapy in adult
      clients with developmental disabilities on the frequency of challenging behavior,
      stereotypic self-stimulating behavior, and positive behaviour; and changes of
      physiological measures. DESIGN: Systematic review. DATA SOURCES: A search of
      electronic databases of published research studies (January 1985-December 2008)
      was conducted, using appropriate search terms. The reference lists and
      bibliographies of retrieved articles were reviewed to identify research not
      located through other search strategies. REVIEW METHODS: Studies that
      investigated the effects of multisensory environment in relation to outcomes were
      examined. Data were extracted independently by two reviewers. Methodological
      quality was also assessed by two reviewers against key quality criteria.
      FINDINGS: One hundred and thirty-two studies were identified from database search
      of which 17 met the inclusion criteria for review. The evidence supports that
      participants' had displayed more positive behaviour after multisensory therapy
      sessions. There is no strong evidence supporting that multisensory therapy could
      help in reducing challenging behaviour or stereotypic self-stimulating behaviour.
      CONCLUSIONS: This systematic review demonstrates a beneficial effect of
      multisensory therapy in promoting participants' positive emotions. While the
      reviewers acknowledge the difficulty in carrying out randomized controlled trial
      in people with developmental disabilities and challenging behavior, the lack of
      trial-derived evidence makes it difficult to arrive at a conclusion of the
      effectiveness of the multisensory therapy. Future study should use well-designed
      randomised controlled trials to evaluate the short and long term effectiveness of
      multisensory therapy. There is also a need for qualitative studies which allow
      the clients to tell the stories of their experiences.

PMID- 19762018
TI  - [Improvised closed suction drainage for surgery in precarious situation: "the
      khmeredon"].

PMID- 19762019
TI  - [The recurrent malaise of general surgeons is neither fatal nor foreordained].

PMID- 19762020
TI  - [Transanal tumor resection using a traction flap].

PMID- 19762021
TI  - [Longitudinal sleeve gastrectomy as a stand-alone bariatric procedure: Results of
      a multicenter retrospective study].
AB  - INTRODUCTION: Sleeve gastrectomy as an isolated procedure is a new option in
      bariatric surgery. The aim of this study was to evaluate its short and medium
      term (2 years) results in a multicenter setting. MATERIALS: This is a
      retrospective study including 446 patients undergoing surgery in 14 teaching,
      private, and public hospitals. RESULTS: The immediate post-operative course were
      uneventful in 83.3% of patients. Minor complications occurred in 10.9% of
      patients and major complications in 5.3%. Suture line leaks occurred in 4.3% of
      the whole series. There was no mortality and the rate of reoperation was 2%.
      Overall mean weight loss after two years was 32 kg and the mean excess weight
      loss was 62%. Weight loss was significantly greater in non super-obese patients
      (p=0.0003). CONCLUSIONS: This study confirms the feasibility of sleeve
      gastrectomy in a multicenter setting; it is efficacious at two years as an
      isolated bariatric procedure for non super-obese patients. It is possible that an
      additional second-stage procedure may be necessary for super-obese patients.

PMID- 19762022
TI  - [Long-term follow-up of the treatment of high anal fistulas using fibrin glue].
AB  - AIM OF THE STUDY: Many of the treatments proposed for trans-sphincteric and
      suprasphincteric anal fistulas are complex and often associated with permanent
      damage to the sphincter mechanism. In this study, we evaluate the long-term
      stability of fistula closure using fibrin glue. MATERIALS AND METHODS: Forty-five
      consecutive patients (mean age 41.5) underwent this procedure. Follow-up was
      obtained from all patients and their primary care physicians by January 1, 2008.
      RESULTS: Mean follow-up was 67 months. All recurrences occurred in the first six
      months after the initial fibrin glue injection procedure; there were no late
      recurrences. CONCLUSION: Long-term follow-up confirmed the safety, efficacy and
      durability of fibrin glue fistula closure.

PMID- 19762023
TI  - [Valuation of innovation: a new challenge for the structures of care, an
      opportunity for everybody...].

PMID- 19762024
TI  - The incremental role of obstructive sleep apnoea on markers of atherosclerosis in
      patients with metabolic syndrome.
AB  - OBJECTIVE: Metabolic syndrome (MS) is associated with subclinical
      atherosclerosis, but the relative role of obstructive sleep apnoea (OSA) is
      largely unknown. The main objective of this study is to determine the impact of
      OSA on markers of atherosclerosis in patients with MS. METHODS: Eighty-one
      consecutive patients with MS according to the Adult Treatment Panel III underwent
      a clinical evaluation, polysomnography, laboratory and vascular measurements of
      carotid intima media thickness (IMT), carotid-femoral pulse wave velocity (PWV)
      and carotid diameter (CD) in a blind fashion. OSA was defined as an apnoea
      hypopnoea index (AHI) > or =15 events/hour. Multiple linear regression was
      performed to determine the variables that were independently associated with the
      vascular parameters. RESULTS: Fifty-one patients (63%) had OSA. No significant
      differences existed in age, sex, MS criteria, and cholesterol levels between
      patients with (MS+OSA) and without OSA (MS-OSA). Compared with MS-OSA patients,
      MS+OSA patients had higher levels of IMT (661+/-117 vs. 767+/-140 microm), PWV
      (9.6+/-1.0 vs. 10.6+/-1.6m/s), and CD (6705+/-744 vs. 7811+/-862 microm) (P<0.001
      for each comparison). Among patients with MS+OSA, all vascular parameters were
      similar in patients with and without daytime sleepiness. The independent
      parameters associated with IMT, PWV, and CD were AHI, abdominal circumference,
      and systolic blood pressure (R(2)=0.42); AHI and systolic blood pressure
      (R(2)=0.38); and AHI, age, abdominal circumference and systolic blood pressure
      (R(2)=0.45), respectively. The R(2) of AHI for IMT, PWV and CD was 0.12, 0.10 and
      0.20, respectively. CONCLUSIONS: OSA is very common and has an incremental role
      in atherosclerotic burden in consecutive patients with MS.

PMID- 19762025
TI  - The role of carotid intima-media thickness assessment in cardiovascular risk
      evaluation in patients with polyvascular atherosclerosis.
AB  - In populational studies, carotid intima-media thickness (CIMT) is a valuable tool
      in the evaluation of cardiovascular (CV) risk. However, there is not much
      evidence on the relation between CIMT, and CV events in patients who have already
      undergone revascularization procedures. AIM: To evaluate the relationship between
      CIMT, atherosclerosis extent and CV event rates in patients with established
      atherosclerosis. METHODS AND RESULTS: Baseline mean-CIMT was assessed in 652
      patients, including 195; 191; 112; 29 with angiographic arterial stenosis >or=50%
      in 1; 2; 3 or 4 territories (coronary, supraaortic, renal and/or lower limb
      arteries), who underwent revascularization procedure in >or=1 arterial territory,
      and in 125 control subjects without significant lesions. For CIMT >or=1.25mm
      (>or=3rd quartile), the sensitivity and specificity of >or=2-territory
      involvement were 81.6% and 81.9%. CV events occurred in 91(14%) subjects. The
      Kaplan-Meier 2-year CV event-free survival was 95.6%; 93.1%; 83.8%; 77% in
      patients with mean-CIMT values in the 1st; 2nd; 3rd and 4th quartile. The
      independent CV adverse event predictors identified in the multivariate Cox
      proportional hazard model were: mean-CIMT >or=1.25mm (RR=2.52; CI=1.5-4.24;
      p=0.001); hs-CRP (RR=1.02; CI=1.0-1.03; p=0.011), claudication (RR=1.58; CI=0.98
      2.57; p=0.062), accumulation of >or=4 traditional risk factors (RR=2.02; CI=1.31
      3.12; p=0.002), 2-3-vessel coronary artery disease (RR=1.95; CI=1.21-3.14;
      p=0.006). Inclusion of CIMT into the stratification model significantly improved
      the prediction of CV event risk (DeltaChi(2)=13.27, p=0.0003). CONCLUSIONS: In
      patients undergoing revascularization procedure(s), CIMT has an important and
      independent contribution to further CV risk stratification. The mean-CIMT value
      >or=1.25mm is associated with 2.5-fold increased risk of adverse CV events.

PMID- 19762026
TI  - Haplotypes and 5A/6A polymorphism of the matrix metalloproteinase-3 gene in
      coronary disease: case-control study and a meta-analysis.
AB  - OBJECTIVE: Matrix metalloproteinase-3 and its gene, MMP3, have been implicated in
      atherosclerotic diseases of coronary arteries. We conducted a haplotype analysis
      to examine the role of common variation of MMP3 in myocardial infarction (MI) and
      a meta-analysis to combine available evidence on the association between the
      5A/6A polymorphism (rs3025058) and coronary diseases. METHODS AND RESULTS:
      Genotype distributions of haplotype-tagging single nucleotide polymorphisms
      (rs522616, rs650108, rs569444, rs635746) and rs3025058 were not significantly
      different between a group with MI (n=3657) and a control group (n=1211) (p> or
      =0.24). Five major haplotypes were established, and their frequencies were not
      substantially different between the case and control groups (p> or =0.11). In a
      meta-analysis of 15 studies (10,061 cases, 8048 controls), the overall risk of
      coronary disease was not different between the carriers of the 5A allele and 6A6A
      genotype of rs3025058 (OR, 1.00; 95% CI, 0.85-1.19). Moderate trends of a reduced
      risk in the 5A allele carriers of European ancestry (OR, 0.87; 95% CI, 0.76-1.00)
      and an increased risk in the 5A allele carriers from East Asia (OR, 1.33; 95% CI,
      0.94-1.90) were observed. CONCLUSIONS: Individual polymorphisms and haplotypes of
      MMP3 were not associated with MI in a German case-control study. Evidence was
      obtained to suggest different risk effects of rs3025058 between Europeans and
      East Asians.

PMID- 19762027
TI  - Computational simulation of simultaneous cortical and trabecular bone change in
      human proximal femur during bone remodeling.
AB  - In this study, we developed a numerical framework that computationally determines
      simultaneous and interactive structural changes of cortical and trabecular bone
      types during bone remodeling, and we investigated the structural correlation
      between the two bone types in human proximal femur. We implemented a surface
      remodeling technique that performs bone remodeling in the exterior layer of the
      cortical bone while keeping its interior area unchanged. A micro-finite element
      (microFE) model was constructed that represents the entire cortical bone and full
      trabecular architecture in human proximal femur. This study simulated and
      compared the bone adaptation processes of two different structures: (1) femoral
      bone that has normal cortical bone shape and (2) perturbed femoral bone that has
      an artificial bone lump in the inferomedial cortex. Using the proposed numerical
      method in conjunction with design space optimization, we successfully obtained
      numerical results that resemble actual human proximal femur. The results revealed
      that actual cortical bone, as well as the trabecular bone, in human proximal
      femur has structurally optimal shapes, and it was also shown that a bone
      abnormality that has little contribution to bone structural integrity tends to
      disappear. This study also quantitatively determined the structural contribution
      of each bone: when the trabecular adaptation was complete, the trabecular bone
      supported 54% of the total load in the human proximal femur while the cortical
      bone carried 46%.

PMID- 19762028
TI  - Dynamic creep and pre-conditioning of the Achilles tendon in-vivo.
AB  - Warm-up exercises are often advocated prior to strenuous exercise, but the warm
      up duration and effect on muscle-tendon behavior are not well defined. The
      gastrocnemius-Achilles tendon complexes of 18 subjects were studied to quantify
      the dynamic creep response of the Achilles tendon in-vivo and the warm-up dose
      required for the Achilles tendon to achieve steady-state behavior. A custom
      testing chamber was used to determine each subject's maximum voluntary
      contraction (MVC) during an isometric ankle plantar flexion effort. The subject's
      right knee and ankle were immobilized for one hour. Subjects then performed over
      seven minutes of cyclic isometric ankle plantar flexion efforts equal to 25-35%
      of their MVC at a frequency of 0.75 Hz. Ankle plantar flexion effort and images
      from dual ultrasound probes located over the gastrocnemius muscle-Achilles tendon
      and the calcaneus-Achilles tendon junction were acquired for eight seconds at the
      start of each sequential minute of the activity. Ultrasound images were analyzed
      to quantify the average relative Achilles tendon strain at 25% MVC force
      (epsilon(25%MVC)) for each minute. The epsilon(25%MVC) increased from 0.3% at the
      start of activity to 3.3% after seven minutes, giving a total dynamic creep of
      ~3.0%. The epsilon(25%MVC) increased by more than 0.56% per minute for the first
      five minutes and increased by less than 0.13% per minute thereafter. Therefore,
      following a period of inactivity, a low intensity warm-up lasting at least six
      minutes or producing 270 loading cycles is required for an Achilles tendon to
      reach a relatively steady-state behavior.

PMID- 19762029
TI  - Exposure to internal muscle tissue loads under the ischial tuberosities during
      sitting is elevated at abnormally high or low body mass indices.
AB  - Deep tissue injury (DTI) is a severe pressure ulcer characteristic of chairfast
      or bedfast individuals, such as those with impaired mobility or neurological
      disorders. A DTI differs from superficial pressure ulcers in that the onset of
      DTI occurs under intact skin, in skeletal muscle tissue overlying bony
      prominences, and progression of the wound continues subcutaneously until skin
      breakdown. Due to the nature of this silently progressing wound, it is highly
      important to screen potentially susceptible individuals for their risk of
      developing a DTI. Abnormally low and high values of the body mass index (BMI)
      have been proposed to be associated with pressure ulcers, but a clear mechanism
      is lacking. We hypothesize that during sitting, exposure to internal muscle
      tissue loads under the ischial tuberosities (IT) is elevated at abnormally high
      or low body mass indices. Our aims in this study were: (a) to develop
      biomechanical models of the IT region in the buttocks that represent an
      individual who is gaining or losing weight drastically. (b) To determine changes
      in internal tissue load measures: principal compression strain, strain energy
      density (SED), principal compression stress and von Mises stress versus the BMI.
      (c) To determine percentage volumes of muscle tissue exposed to critical levels
      of the above load measures, which were defined based on our previous animal and
      tissue engineered model experiments: strain>or=50%, stress>or=2 kPa, SED>or=0.5
      kPa. A set of 21 finite element models, which represented the same individual,
      but with different BMI values within the normal range, above it and below it, was
      solved for the outcome measures listed above. The models had the same IT shape,
      size, distance between the IT, and (non-linear) mechanical properties for all
      soft tissues, but different thicknesses of gluteus muscles and fat tissue layers,
      corresponding to the BMI level. The resulted data indicated a trend of
      progressive increase in internal tissue loading, particularly in volumetric
      exposure to critical loading for BMI values outside the 17<or=BMI<or=22 kg/m(2)
      range, supporting our hypothesis for this study. We concluded that exposure to
      internal muscle tissue loads under the IT during sitting is optimally reduced at
      the low-normal BMI range, which is important not only in the context of DTI
      research, but also for understanding general sitting biomechanics.

PMID- 19762030
TI  - Validation of an ultra high pressure liquid chromatographic method for the
      determination of biologically active amines in food.
AB  - Biologically active amines include the so called biogenic amines, such as
      histamine, tyramine and cadaverine, and polyamines such as spermidine and
      spermine. Ultra high pressure liquid chromatography (UHPLC) is a new generation
      of separation techniques that takes full advantage of chromatographic principles
      to increase speed flow which drastically reduce analysis time. The aim of the
      present work was to validate a rapid method of UHPLC to detect the presence of
      biogenic amines and polyamines in food. Different food matrixes (wine, fish,
      cheese, and dry fermented sausage) were used in order to test the versatility of
      the method. The UHPLC method described in this article has been demonstrated as a
      reliable procedure to determine 12 biogenic amines and polyamines in less than
      7min of chromatographic elution. The method provides a satisfactory linearity and
      chromatographic sensitivity with a detection limit lower than 0.2mg/L and a
      determination limit falling below 0.3mg/L for all amines. The precision, in terms
      of relative standard deviation, was lower than 5% and the accuracy, as mean
      recovery, was between 93% and 98%, depending on the food matrix.

PMID- 19762031
TI  - An experimental design approach using response surface techniques to obtain
      optimal liquid chromatography and mass spectrometry conditions to determine the
      alkaloids in Meconopsi species.
AB  - A statistic approach using response surface methodology (RSM) for optimization of
      the ultra-high performance liquid chromatography (UHPLC) gradient and ionization
      response of electrospray ionization mass spectrometry (ESI-MS) to analyze the
      main alkaloids from the plant matrices of six Meconopsi species is presented. The
      optimization was performed with Box-Behnken designs (BBD) and the multicriteria
      response variables were described using global Derringer's desirability. Four
      parameters of UHPLC and six major parameters of ESI-MS were investigated for
      their contribution to analytes separation and response, leading to a total of 27
      and 54 experiments being performed for each instrument, respectively.
      Quantitative analysis of four main alkaloids in nine samples from six Meconopsis
      species was employed to evaluate the statistical significance of the parameters
      on UHPLC-QTOF/ESI-MS analytes response. The results indicated that the optimized
      UHPLC-QTOF-MS method is very sensitive with the limit of detections (LODs)
      ranging from 0.5 to 0.1 ng/ml. The overall intra-day and the inter-day variations
      were less than 2.45%. The recovery of the method was in the range of 94.3-104.8%
      with RSD less than 4.0%. This approach has important implication in sensitivity
      enhancement of the ultra-trace determination of alkaloids from complex matrixes
      in the fields of natural products, metabolomics and pharmacokinetics.

PMID- 19762032
TI  - Development and validation of a normal-phase high-performance thin layer
      chromatographic method for the analysis of sulfamethoxazole and trimethoprim in
      co-trimoxazole tablets.
AB  - Pneumocystis carinii pneumonia (PCP) is often the ultimate mortal cause for
      immunocompromised individuals, such as HIV/AIDS patients. Currently, the most
      effective medicine for treatment and prophylaxis is co-trimoxazole, a synergistic
      combination of sulfamethoxazole (SMX) and trimethoprim (TMP). In order to ensure
      a continued availability of high quality co-trimoxazole tablets within resource
      limited countries, Medicines Regulatory Authorities must perform quality control
      of these products. However, most pharmacopoeial methods are based on high
      performance liquid chromatographic (HPLC) methods. Because of the lack of
      equipment, the Tanzania Food and Drugs Authority (TFDA) laboratory decided to
      develop and validate an alternative method of analysis based on the TLC technique
      with densitometric detection, for the routine quality control of co-trimoxazole
      tablets. SMX and TMP were separated on glass-backed silica gel 60 F(254) plates
      in a high-performance thin layer chromatograph (HPTLC). The mobile phase was
      comprised of toluene, ethylacetate and methanol (50:28.5:21.5, v:v:v). Detection
      wavelength was 254 nm. The R(f) values were 0.30 and 0.61 for TMP and SMX,
      respectively. This method was validated for linearity, precision, trueness,
      specificity and robustness. Cochran's criterion test indicated homoscedasticity
      of variances for the calibration data. The F-tests for lack-of-fit indicated that
      straight lines were adequate to describe the relationship between spot areas and
      concentrations for each compound. The percentage relative standard deviations for
      repeatability and time-different precisions were 0.98 and 1.32, and 0.83 and 1.64
      for SMX and TMP, respectively. Percentage recovery values were 99.00%+/-1.83 and
      99.66%+/-1.21 for SMX and TMP, respectively. The method was found to be robust
      and was then successfully applied to analyze co-trimoxazole tablet samples.

PMID- 19762033
TI  - Comparison on photo-initiators for the preparation of methacrylate monolithic
      columns for capillary electrochromatography.
AB  - The synthesis of lauryl methacrylate monoliths for capillary
      electrochromatography by UV polymerization using several free-radical initiators
      (alpha,alpha'-azobisisobutyronitrile, 2,2-dimethoxy-2-phenylacetophenone,
      dibenzoyl peroxide (BPO) and lauroyl peroxide (LPO)) has been investigated. Using
      a 1,4-butanediol/1-propanol mixture as porogenic solvent, the influence of each
      initiator and its content on the morphological and electrochromatographical
      properties of beds was evaluated. Under their respective optimum content,
      satisfactory separations of a test mixture of PAHs with similar efficiencies
      (minimum plate heights of 8.0-12.7 microm obtained from Van Deemter plots) were
      achieved for the four investigated photo-initiators. The columns photo
      polymerized with LPO provided the best compromise between chromatographic
      performance and analysis time. Moreover, this initiator showed a fine control in
      the column retention properties. The resulting monolithic columns exhibited a
      good run-to-run repeatability in the tested chromatographic parameters (RSD<2.4%)
      for all initiators investigated; and satisfactory column-to-column repeatability
      (RSD<6.0%), except for beds photo-polymerized with BPO (RSD<10.8%).

PMID- 19762034
TI  - Solid-phase microextraction under controlled agitation conditions for rapid on
      site sampling of organic pollutants in water.
AB  - An electric drill coupled with a solid-phase microextraction (SPME)
      polydimethylsiloxane (PDMS) fiber or a PDMS thin film was used for rapid sampling
      of polycyclic aromatic hydrocarbons (PAHs) in aqueous samples. Laboratory
      experiments demonstrated that the sampling rates of SPME fiber and thin film can
      be predicted theoretically. Compared with the SPME fiber, the PDMS thin film
      active sampler exhibited a higher sampling rate and much better sensitivity due
      to its higher surface-to-volume ratio and its larger extraction phase volume. The
      amount of the analytes extracted by the thin film was around 100 times higher
      than those obtained by fiber, for both 5 min rapid sampling and equilibrium
      extraction. A new thin film active sampler was then developed for rapid on-site
      water sampling. The sampling kit included a portable electric drill, a copper
      mesh pocket, a piece of thin film, and a liner. Laboratory experiments indicated
      that the sampling remained in the linear uptake phase with this sampler to 8 min
      for the PAHs. Field test illustrated that this novel sampler was excellent for
      rapid on-site water sampling due to its short sampling period, high sampling
      efficiency and durability The thin film sampling kit facilitates on-site
      sampling, sample preparation, storage and transport. This new sampler is more
      user-friendly and easier to commercialize than previous samplers.

PMID- 19762035
TI  - Influence of the polymerisation time on the porous and chromatographic properties
      of monolithic poly(1,2-bis(p-vinylphenyl))ethane capillary columns.
AB  - In order to elucidate the effect of the polymerisation time on the morphology of
      styrene based monolithic support materials, continuous poly(1,2-bis(p
      vinylphenyl))ethane (BVPE) rods were synthesised in 1.0ml glass vials by
      thermally initiated free radical polymerisations of BVPE in the presence of
      porogens (toluene, decanol) and a,a'-azoisobutyronitrile (AIBN) as initiator at
      65 degrees C for different polymerisation times (60, 90, 150, 300 and 600min).
      Porosity parameters like pore-size-distribution and total porosity were
      investigated by mercury intrusion porosimetry, while the specific surface area of
      the BVPE monolithic supports was determined by N(2)-adsorption (BET)
      measurements. An untypical bimodal pore-size-distribution comprising a high
      fraction of both mesopores (2-50nm) and macropores (mainly flow-channels in the
      micrometer range) was observed as a result of the stepwise decrease of the
      polymerisation time. In consequence of the significant changes of the pore-size
      profile, shortening the polymerisation time also resulted in enhanced total
      porosity due to enlarged flow-channel diameters and increased surface area
      according to the presence of a considerable amount of mesopores. Results upon the
      porosity profile of the support are further confirmed by SEM images of monoliths
      polymerised for different time periods. Since mesoporosity and high surface area
      of the chromatographic support material play key roles in the interaction and
      thus retention of low-molecular-weight compounds, polymerisation time should also
      affect the chromatographic properties and applicability of these polymers. To
      study the influence of the polymerisation time towards the separation efficiency
      of small molecules on BVPE capillary columns (200microm I.D., 8cm), a mixture of
      homologous alkylbenzenes was chosen for column evaluation. In accordance with the
      observations of the porous properties of BVPE stationary phases, the rapid and
      high resolution separation of a range of low-molecular-weight compounds on
      monolithic BVPE supports were successfully realised. The methodical reduction of
      the polymerisation time has been demonstrated to be a simple and effective tool
      to tailor the porous properties of organic monoliths to provide novel polymer
      based stationary phases with porous properties adequate for the rapid and high
      resolution chromatography of small organic molecules.

PMID- 19762036
TI  - Rich aggregate morphologies induced by organic salts in aqueous solutions of a
      cationic gemini surfactant with a short spacer.
AB  - Various aggregates, such as spherical and elongated micelles, tubular and rodlike
      aggregates, as well as vesicles, are induced by adding sodium 2
      naphthalenesulfonate (SNphs) or sodium benzenesulfonate (SBzs) into the aqueous
      solution of a gemini surfactant C12C2C12(Me) (1,2-ethanediyl-bis
      (dodecyldimethylammonium bromide)). The aggregate morphology strongly depends on
      the added amount of the organic salts. Among the various aggregates, the
      elongated micelle and the tubular aggregate have larger solubilizing capacities
      than those with the other morphologies. However, SNphs and SBzs cannot induce
      similar aggregate transitions for the systems of C12CsC12(Me) (s=6, 8, 12). The
      possible mechanism of these phenomena is proposed based on the results of UV
      spectra and 1H NMR measurements and the molecular packing geometry rule.

PMID- 19762037
TI  - One-pot synthesis of organophilic layered double hydroxides (LDHs) containing
      aliphatic carboxylates: extended "homogeneous precipitation" method.
AB  - One-pot synthesis of aliphatic carboxylate/LDH hybrids (org-LDHs) was
      accomplished via the so-called "homogeneous precipitation" method developed for
      preparing carbonate-type layered double hydroxides (CO(3)(2-) LDHs) with ammonia
      releasing reagents such as hexamethylenetetramine (HMT) and urea. An aqueous
      solution of an aliphatic carboxylate (C2-C18) was added to a mixed aqueous
      solution of metal salts and HMT and then heated at 140-160 degrees C in a
      pressure vessel for 1day. Two kinds of LDHs were investigated: MgAl-LDH and NiAl
      LDH. We found that only aliphatic carboxylates longer than decanoate (C10) and
      dodecanoate (C12) were incorporated successfully in the MgAl-LDH and NiAl-LDH
      interlayers without any CO(3)(2-) contamination, respectively. Shorter
      carboxylates were not incorporated, only yielding CO(3)(2-)LDHs. Isolation of the
      hydrophobic org-LDH phase from the aqueous medium containing carbonate ions was
      assumed to be the main reason for the lack of CO(3)(2-) contamination in the org
      LDHs having longer-alkyl carboxylates. This method was also used successfully for
      preparing MgAl-LDHs containing dodecylbenzene sulfonate(DBS), a sulfonate-type
      anionic surfactant.

PMID- 19762038
TI  - Wake and sleep EEG provide biomarkers in depression.
AB  - Both wake and sleep electroencephalogram (EEG) provide biomarkers of depression
      and antidepressive therapy, respectively. For a long time it is known that EEG
      activity is altered by drugs. Quantitative EEG analysis helps to delineate
      effects of antidepressants on brain activity. Cordance is an EEG measure with a
      superior correlation with regional brain perfusion. Prefrontal quantitative EEG
      cordance appears to be a predictor of the response to antidepressants. Sleep EEG
      shows characteristic changes in depression as impaired sleep continuity,
      desinhibition of REM sleep and changes of nonREM sleep. Elevated REM density (a
      measure for frequency of rapid eye movements) characterizes an endophenotype in
      family studies of depression. REM-sleep changes including a more distinct REM
      rebound after sleep deprivation are found in animal models of depression. Most
      antidepressants suppress REM sleep in depressed patients, normal controls and
      laboratory animals. REM suppression appears to be a distinct, but not an absolute
      requirement for antidepressive effects of a compound. Sleep-EEG variables like
      REM latency or certain clusters of variables were shown to predict the response
      to the treatment with a certain antidepressant or even the course of the disorder
      for several years. Some of these predictive sleep-EEG markers of the longterm
      course of depression appear to be closely related to hypothalamo-pituitary
      adrenocortical system activity.

PMID- 19762039
TI  - Sleep actigraphy pattern and behavioral/emotional difficulties in kindergarten
      children: association with hypothalamic-pituitary-adrenocortical (HPA) activity.
AB  - BACKGROUND: Various studies of adult endocrinology and sleep show close
      connections between poor sleep quality, deterioration of the HPA axis and
      negative psychological characteristics. However, the extent to which these
      associations may have already emerged and developed in childhood remains unclear.
      METHODS: A total of 82 preschoolers (age 4.91+/-0.48) underwent activity
      monitoring for seven consecutive days and nights, wearing a digital movement
      measuring instrument. Additionally, on the first and on the last morning of sleep
      registration, the activity of the HPA axis was assessed via the amount of
      cortisol in the saliva. Psychological and behavioral assessments were also made.
      RESULTS: Three sub-groups of good (22%), normal (58.5%) and poor (19.5%) sleepers
      were distinguished. Poor sleep patterns were associated with higher HPA activity
      and with behavioral/emotional difficulties. CONCLUSIONS: The interplay between
      unfavorable sleep patterns, deterioration of the HPA axis and
      behavioral/emotional difficulties is already apparent in pre-school children.

PMID- 19762040
TI  - Interobserver agreement for noninvasive bladder pressure flow recording with
      penile cuff.
AB  - PURPOSE: We assessed variability in interpreting noninvasive measurements of
      bladder pressure and urine flow between experienced and novice users of the
      penile cuff. MATERIALS AND METHODS: Urodynamicists at 6 sites were asked to use
      the penile cuff test as part of clinical assessment in 30 men presenting with
      lower urinary tract symptoms. After a short training period they measured maximum
      flow rate and cuff interruption pressure from penile cuff test recordings to
      enable categorization of bladder outlet obstruction using a nomogram. Similar
      measurements were then made on the same traces by 2 expert observers from the
      originating center. Interobserver differences were assessed. RESULTS: Complete
      agreement on obstruction categorization was seen in 77% of subjects, which
      increased to 86% when plots positioned on category boundary lines were allocated
      to the favored category. The 95% confidence limits of interobserver variability
      in maximum flow rate and cuff interruption pressure measurements were +/- 1.7 ml
      per second and +/- 13 cm H(2)O, respectively, although a small number of studies
      yielded discrepancies between observers that were larger than expected. They
      arose from complex recordings but were equally likely between experts as between
      expert and novice. Investigation of the causes suggested in some cases how such
      discrepancies may be avoided in the future. CONCLUSIONS: The excellent level of
      agreement in measurement and categorization after a short training period
      suggests that introducing the penile cuff test as part of assessment in men with
      lower urinary tract symptoms would be straightforward.

PMID- 19762041
TI  - Medium term outcome of laparoscopic sacrocolpopexy with xenografts compared to
      synthetic grafts.
AB  - PURPOSE: We compared the medium term anatomical and subjective outcome, and graft
      related complications after sacrocolpopexy for apical vaginal prolapse using
      xenogenic or polypropylene grafts. MATERIALS AND METHODS: We prospectively
      studied 50 consecutive patients who underwent laparoscopic sacrocolpopexy with
      porcine grafts of small intestinal submucosa (21) or dermal collagen (29). We
      compared these patients to 100 consecutive controls in whom polypropylene was
      used, and underwent surgery before (50) or after (50) the cases. The primary
      outcome was anatomical cure (stage I or less at any compartment). Secondary
      outcomes were graft related complications, subjective cure and quality of life
      evaluated by clinical examination, standardized interview and prolapse specific
      questionnaire, respectively. RESULTS: At study closure 129 (86%) patients were
      available for functional evaluation and 104 (67%) were available for anatomical
      evaluation. Mean postoperative followup (+/-33 months) and baseline
      characteristics except age were comparable. The overall anatomical failure rate
      was comparable (49% vs 34%, p = 0.053) but failures at the vault (21% vs 3%, p
      <0.01) and posterior compartment (36% vs 19%, p <0.05) were more frequent in the
      xenograft group. There were 6 reoperations including secondary laparoscopic
      sacrocolpopexy (5) and cystocele repair (1), all confined to the xenograft group
      (p <0.01). Graft related complications were equally frequent (11%) in the
      xenograft and polypropylene groups. The reoperation rate for graft related
      complications was not different (xenograft 3% vs controls 11%, p = 0.20). There
      were no differences in functional outcome and quality of life between xenografts
      and controls. CONCLUSIONS: While overall anatomical failure was comparable,
      sacrocolpopexy using xenograft was associated with more apical failures and
      reoperations for prolapse than with polypropylene without differences in
      functional outcome. The use of xenografts did not decrease the number of graft
      related complications.

PMID- 19762042
TI  - A multicenter study on the perineal versus penoscrotal approach for implantation
      of an artificial urinary sphincter: cuff size and control of male stress urinary
      incontinence.
AB  - PURPOSE: In a single center retrospective study we previously reported superior
      dry rates and fewer artificial urinary sphincter revisions when the sphincter
      cuff was placed via the traditional perineal approach compared with a penoscrotal
      approach. A multicenter study was performed to compare the approaches further and
      explain the disparity in outcomes. MATERIALS AND METHODS: We performed a
      retrospective review of 158 patients who underwent these procedures from April
      1987 to October 2007 at 4 centers. RESULTS: During 184 surgeries in 158 patients
      201 artificial urinary sphincter cuffs were placed (90 penoscrotal and 111
      perineal). Among patients with known followup the completely dry rate for single
      cuff artificial urinary sphincters was 17 of 62 (27.4%) in the penoscrotal group
      and 41 of 93 (44.1%) in the perineal group (p = 0.04). Continued incontinence
      necessitated subsequent tandem cuff in 7 of the 62 (11.3%) penoscrotal cases
      compared to only 5 of the 93 (5.4%) perineal cases. Cuff size in the penoscrotal
      group was 5.0 cm in 1 patient (1.1%), 4.5 cm in 11 (12.2%) and 4.0 cm in 78
      (86.7%). Cuff size in the perineal group was 5.5 cm in 1 patient (0.9%), 5.0 cm
      in 8 (7.2%), 4.5 cm in 30 (27.0%) and 4.0 cm in 72 (64.9%). CONCLUSIONS: There
      appears to be a higher completely dry rate with fewer subsequent tandem cuff
      additions with the perineal approach compared to the penoscrotal approach. This
      disparity may be explained by a more proximal artificial urinary sphincter cuff
      placement in the perineal group as evidenced by a larger cuff size.

PMID- 19762043
TI  - A prospective study of risk factors for nephrolithiasis after Roux-en-Y gastric
      bypass surgery.
AB  - PURPOSE: Roux-en-Y gastric bypass surgery has become an increasingly common form
      of weight management. Early retrospective reviews have suggested that new onset
      nephrolithiasis develops in some patients after undergoing Roux-en-Y gastric
      bypass. We present a prospective longitudinal study to assess risk factors for
      nephrolithiasis after Roux-en-Y gastric bypass. MATERIALS AND METHODS: A total of
      45 morbidly obese patients scheduled to undergo Roux-en-Y gastric bypass surgery
      were enrolled in this prospective study between November 2006 and November 2007.
      Exclusion criteria included history of nephrolithiasis or inflammatory bowel
      disease. Serum uric acid, parathyroid hormone, calcium, albumin, and creatinine
      and 24-hour urine collections were obtained within 6 months before Roux-en-Y
      gastric bypass, and at 6 to 12 months postoperatively. A Wilcoxon signed-rank
      test was used to compare preoperative and postoperative serum laboratory values
      and 24-hour urine values. McNemar's test was used to determine if the percent of
      abnormal values underwent a statistically significant change after Roux-en-Y
      gastric bypass. For both statistical methods a p value was calculated for the
      change in each variable with p <0.05 considered statistically significant.
      RESULTS: Statistically significant changes included increased urinary oxalate and
      calcium oxalate supersaturation, and decreased urinary citrate and total urinary
      volume postoperatively. A statistically significant percentage of patients
      exhibited decreased urinary calcium, while a statistically significant percentage
      of patients experienced increased urinary oxalate and calcium oxalate
      supersaturation. CONCLUSIONS: Our prospective study demonstrated multiple factors
      that increase the relative risk of nephrolithiasis after Roux-en-Y gastric
      bypass. These changes may make stone formation after Roux-en-Y gastric bypass
      increasingly likely and pose an ongoing challenge in the realm of urology.

PMID- 19762044
TI  - Ureteroileocecal appendicostomy based urinary reservoir in irradiated and
      nonirradiated patients.
AB  - PURPOSE: The ureteroileocecal appendicostomy reservoir is designed to potentially
      decrease the morbidity of continent diversion, particularly in previously
      irradiated patients. We report our experience with this reservoir to compare
      complications in irradiated and nonirradiated patients. MATERIALS AND METHODS:
      The records of 52 consecutive patients who underwent ureteroileocecal
      appendicostomy diversion between March 2001 and January 2008 were evaluated.
      Outcomes were analyzed according to whether patients received radiation therapy
      to the pelvis. Complications were reported as early (within 90 days of surgery)
      or late. RESULTS: Overall 29 patients received radiation therapy. The incidence
      of early complications requiring operative intervention was 14%, including 2
      patients (9%) with and 5 (17%) without radiation (p = 0.68). All except 1
      reoperation was done to revise the stoma. Early urinary tract infections
      developed in 17% of nonirradiated and 28% of irradiated patients (p = 0.51). The
      most common late complication was stomal stenosis requiring dilation on an
      outpatient basis, which occurred in 21% of patients, including 4 with (17%) and 7
      without (24%) radiation (p = 0.74). Late ureteral complications requiring
      intervention were reported in 15% of renal units, including 2 of 44 without (5%)
      and 6 of 56 with (11%) radiation (p = 0.21). CONCLUSIONS: Ureteroileocecal
      appendicostomy is a safe, effective technique for continent cutaneous urinary
      diversion in heavily irradiated patients. Complication rates did not
      significantly differ between irradiated and nonirradiated patients, and appear
      improved compared to those in previous reports.

PMID- 19762045
TI  - Editorial comment.

PMID- 19762046
TI  - Editorial comment.

PMID- 19762047
TI  - Transperitoneal laparoscopic prostatectomy does not increase small bowel within
      the target volume for postoperative radiotherapy.
AB  - PURPOSE: Laparoscopic or robot assisted laparoscopic radical prostatectomy is
      often performed via a transperitoneal approach for prostate cancer, in contrast
      to open retropubic radical prostatectomy. Theoretically transgressing the
      peritoneum may introduce small bowel loops into the pelvis, increasing the risk
      of small bowel injury with adjuvant radiotherapy. We compared the incidence of
      small bowel within the planning target volume for radiotherapy to the prostate
      bed in patients who underwent open retropubic and laparoscopic radical
      prostatectomy. MATERIALS AND METHODS: A total of 25 patients recently treated
      with laparoscopic radical prostatectomy prospectively provided consent to undergo
      radiotherapy planning computerized tomography simulation to assess the incidence
      of small bowel within the prostate bed planning target volume. These studies were
      compared to radiotherapy planning computerized tomography in 50 patients who
      underwent open retropubic radical prostatectomy and received adjuvant or salvage
      radiotherapy for prostate cancer. For all computerized tomography images 1
      blinded observer delineated the distal small bowel loops and 1 blinded radiation
      oncologist delineated the superior extent of clinical and planning target
      volumes. RESULTS: The overlap rate between small bowel and planning target volume
      was 16% in the laparoscopic and open radical prostatectomy groups (p = 0.579).
      CONCLUSIONS: There is no difference between transperitoneal laparoscopic and open
      retropubic radical prostatectomy in the incidence of small bowel within the
      planning target volume for radiotherapy to the prostate bed. Thus, patients who
      undergo transperitoneal laparoscopic radical prostatectomy do not face a higher
      risk of toxicity or compromise due to adjuvant or salvage radiotherapy should
      they require it.

PMID- 19762048
TI  - The use of a surgical patch in the prevention of lymphoceles after
      extraperitoneal pelvic lymphadenectomy for prostate cancer: a randomized
      prospective pilot study.
AB  - PURPOSE: Pelvic lymphadenectomy is frequently performed simultaneously with
      radical prostatectomy to determine lymph node status and the most frequently
      recorded postoperative complication is the development of a symptomatic
      lymphocele. This study evaluated TachoSil as an adjunct treatment in preventing
      lymphoceles after extraperitoneal pelvic lymphadenectomy for prostate cancer.
      MATERIALS AND METHODS: A total of 60 consecutive patients who had undergone
      radical prostatectomy and pelvic lymphadenectomy were prospectively enrolled in
      this study. The patients were randomly assigned to a standard technique with the
      use of clips and electrocoagulation plus TachoSil, or to standard technique only.
      All patients underwent ultrasound examination on postoperative days 7, 14 and 28
      to test for the development of symptomatic or asymptomatic lymphoceles. Drainage
      volume and duration were also recorded. RESULTS: The baseline characteristics of
      the 2 randomized groups were well matched. Those patients in whom we used
      TachoSil showed a lower drainage volume with a mean total volume of 64 +/- 45 ml
      (range 0 to 110) vs 190 +/- 62.72 ml (range 70 to 270, p = 0.009), and had
      significantly fewer symptomatic and asymptomatic lymphoceles (5 vs 19, p =
      0.001). Only 5 percutaneous surgical procedures to drain the lymphoceles proved
      necessary, 1 of which occurred in the group with TachoSil. CONCLUSIONS: TachoSil
      seems to provide a useful additional treatment option for reducing drainage
      volume and preventing lymphocele development after extraperitoneal radical
      retropubic prostatectomy with pelvic lymphadenectomy.

PMID- 19762049
TI  - Clinicopathological study of regressed testicular tumors (apparent extragonadal
      germ cell neoplasms).
AB  - PURPOSE: Testicular germ cell tumors sometimes regress spontaneously and manifest
      exclusively by metastasis. We report our experience with extragonadal germ cell
      tumors of probable testicular origin to study the frequency of this entity, and
      clinical, ultrasound and histopathological correlations in a series of patients.
      MATERIALS AND METHODS: A retrospective 16-year review of 1.2 million inhabitants
      in Spain revealed 17 with regressed testicular tumors treated at a total of 4
      institutions. We analyzed clinical information, ultrasound features and
      histopathological characteristics of testicular lesions and metastasis, and
      highlight the main findings. RESULTS: A primary testicular origin was confirmed
      in all cases. This entity is more common than initially suspected since it
      accounts for 4% of consecutive germ cell tumors. Clinical manifestations varied
      according to metastatic site with an abdominal palpable mass (47% of cases), loin
      pain (35%) and transient testicular pain (29%) the most common complaints. No
      evidence of testicular neoplasms was found on physical examination in any case.
      Metastasis histology was nonseminomatous in 53% of cases, pure seminoma in 29%
      and mixed in 18%. The most common ultrasound features were calcifications in 65%
      of cases, hyperechogenic linear images in 59% and hypoechogenic nodular areas in
      41%. Histological findings consisted of fibrotic areas in 100% of cases,
      hemosiderin deposits in 65%, seminiferous tubule atrophy in 59% and psammoma
      bodies in 29%. In testicular parenchyma or spermatic chord intratubular neoplasms
      and viable tumor foci were also noted (47% and 41% of cases, respectively).
      CONCLUSIONS: Spontaneous regression of a germ cell testicular tumor should be
      considered in each patient with extragonadal germ cell neoplasms. Ultrasound
      diagnosis of and surgical treatment for these primary testicular tumors appear
      critical to prevent relapse because residual disease develops in a significant
      proportion of cases.

PMID- 19762050
TI  - Editorial comment.

PMID- 19762051
TI  - Gastric band placement for obesity is not associated with increased urinary risk
      of urolithiasis compared to bypass.
AB  - PURPOSE: Obesity is associated with multiple health risks. Bariatric surgery is a
      treatment for clinically severe obesity and is known to increase urolithiasis
      risk. However, trends in risk over time are not well characterized. Moreover
      little attention has been devoted to laparoscopic gastric band placement. A
      comparison of urinary risk of urolithiasis after the Roux-en-Y and gastric
      banding procedures was performed. MATERIALS AND METHODS: We evaluated 24-hour
      urine collections from 39 subjects (11 male and 28 female, mean age 51 years)
      after bariatric surgery. Of these subjects 27 underwent Roux-en-Y gastric bypass
      and 12 had gastric banding procedures. Mean time since surgery was 3.4 and 2.1
      years for the Roux-en-Y gastric bypass and gastric banding groups, respectively.
      RESULTS: Urine volume was low in both groups (less than 1.5 l daily). Urinary
      calcium excretion was lower (p = 0.001) in the Roux-en-Y gastric bypass (100 mg
      daily) vs the gastric banding group (191 mg daily). After Roux-en-Y gastric
      bypass surgery 48% had a urinary oxalate of 45 mg daily or more compared to 25%
      after gastric banding. Urinary citrate was less than 370 mg daily for 14 subjects
      in the Roux-en-Y gastric bypass and 1 in the gastric banding group. All patients
      were taking calcium supplements. Dietary intake of high oxalate foods did not
      correlate with urinary oxalate excretion or with hyperoxaluria. CONCLUSIONS: Our
      study confirms the risk of urinary stones following the Roux-en-Y gastric bypass
      procedure as a result of hyperoxaluria, low urine volume and hypocitraturia.
      Those with gastric banding placement had low urine volumes. Future studies should
      elucidate the effect of nutrition and/or pharmacological therapy on stone risk of
      both surgeries as their incidence increases.

PMID- 19762052
TI  - Functional restoration of penis with partial defect by scrotal skin flap.
AB  - PURPOSE: We investigated a reconstructive method with better sensory and erectile
      function for partial penile defects and report our long-term results of surgical
      correction using scrotal skin flaps. MATERIALS AND METHODS: We retrospectively
      analyzed the records of 18 patients with penile defects referred to us between
      1992 and 2007. All cases were treated with a scrotal skin flap initially to
      repair the secondary defect after penile elongation. RESULTS: Of the 18 cases
      treated during the 15-year period the mechanism of primary injury was
      circumcision in 3, animal bite in 9 and penile tumor dissection in 6. Penile
      elongation, division of the suspensory ligament and scrotal skin flaps achieved
      penile augmentation and enhancement. Six cases were treated with a bilateral
      scrotal skin flap supplied by the anterior scrotal artery and 12 were repaired
      with a total anterior scrotal skin flap supplied by the anterior and posterior
      scrotal arteries. Penile length in the flaccid and erectile states was obviously
      increased postoperatively (p <0.05). All patients were followed 1 to 9 years
      (mean 2.3) postoperatively. Deep and superficial sensation recovered and erectile
      function was retained. Of the 18 patients 15 reported satisfied sexual
      intercourse during the 0.5 to 5-year followup. CONCLUSIONS: The method of
      correcting partial penile defect using scrotal skin flaps is effective and simple
      according to our long-term experience. This method achieves reasonable cosmesis
      and penile length in most cases with better sensory and erectile function.

PMID- 19762053
TI  - Stress induced hypothalamus-pituitary-adrenal axis responses and disturbances in
      psychological profiles in men with chronic prostatitis/chronic pelvic pain
      syndrome.
AB  - PURPOSE: Chronic pelvic pain in men has a strong relationship with
      biopsychosocial stress and central nervous system sensitization may incite or
      perpetuate the pain syndrome. We evaluated patients and asymptomatic controls for
      psychological factors and neuroendocrine reactivity under provoked acute stress
      conditions. MATERIALS AND METHODS: Men with pain (60) and asymptomatic controls
      (30) completed psychological questionnaires including the Perceived Stress, Beck
      Anxiety, Type A behavior and Brief Symptom Inventory for distress from symptoms.
      Hypothalamic-pituitary-adrenal axis function was measured during the Trier Social
      Stress Test with serum adrenocorticotropin hormone and cortisol reactivity at
      precise times, before and during acute stress, which consisted of a speech and
      mental arithmetic task in front of an audience. The Positive and Negative
      Affective Scale measured the state of emotions. RESULTS: Patients with chronic
      pelvic pain had significantly more anxiety, perceived stress and a higher profile
      of global distress in all Brief Symptom Inventory domains (p <0.001), scoring in
      the 94th vs the 49th percentile for controls (normal population). Patients showed
      a significantly blunted plasma adrenocorticotropin hormone response curve with a
      mean total response approximately 30% less vs controls (p = 0.038) but no
      differences in any cortisol responses. Patients with pelvic pain had less
      emotional negativity after the test than controls, suggesting differences in
      cognitive appraisal. CONCLUSIONS: Men with pelvic pain have significant
      disturbances in psychological profiles compared to healthy controls and evidence
      of altered hypothalamic-pituitary adrenal axis function in response to acute
      stress. These central nervous system observations may be a consequence of
      neuropsychological adjustments to chronic pain and modulated by personality.

PMID- 19762054
TI  - Regulation of malate metabolism in grape berry and other developing fruits.
AB  - Organic acids are present in all plants, supporting numerous and varied facets of
      cellular metabolism. The type of organic acid found, and the levels to which they
      accumulate are extremely variable between species, developmental stages and
      tissue types. Acidity plays important roles in the organoleptic properties of
      plant tissues, where examples of both enhanced and reduced palatability can be
      ascribed to the presence of specific organic acids. In fruits, sourness is
      generally attributed to proton release from acids such as citric, malic, oxalic,
      quinic, succinic and tartaric, while the anion forms each contribute a distinct
      taste. Acidity imposes a strong influence on crop quality, and is an important
      factor in deciding the harvest date, particularly for fruits where acidity is
      important for further processing, as in wine grapes. In the grape, as for many
      other fruits, malate is one of the most prevalent acids, and is an important
      participant in numerous cellular functions. The accumulation of malate is thought
      to be due in large part to de novo synthesis in fruits such as the grape, through
      metabolism of assimilates translocated from leaf tissues, as well as
      photosynthetic activity within the fruit itself. During ripening, the processes
      through which malate is catabolised are of interest for advancing metabolic
      understanding, as well as for potential crop enhancement through agricultural or
      molecular practices. A body of literature describes research that has begun to
      unravel the regulatory mechanisms of enzymes involved in malate metabolism during
      fruit development, through exploration of protein and gene transcript levels.
      Datasets derived from a series of recent microarray experiments comparing
      transcript levels at several stages of grape berry development have been
      revisited, and are presented here with a focus on transcripts associated with
      malate metabolism. Developmental transcript patterns for enzymes potentially
      involved in grape malate metabolism have shown that some flux may occur through
      pathways that are less commonly regarded in ripening fruit, such as aerobic
      ethanol production. The data also suggest pyruvate as an important intermediate
      during malate catabolism in fruit. This review will combine an analysis of
      microarray data with information available on protein and enzyme activity
      patterns in grapes and other fruits, to explore pathways through which malate is
      conditionally metabolised, and how these may be controlled in response to
      developmental and climatic changes. Currently, an insufficient understanding of
      the complex pathways through which malate is degraded, and how these are
      regulated, prevents targeted genetic manipulation aimed at modifying fruit malate
      metabolism in response to environmental conditions.

PMID- 19762055
TI  - Phenylpropanoid polyamine conjugate biosynthesis in Arabidopsis thaliana flower
      buds.
AB  - Phenylpropanoid polyamine conjugates have been identified in flowers of many
      plant species. Their presence in Arabidopsis thaliana has only been recently
      established in flower buds and pollen grains. Annotation and location of a cation
      dependent O-methyltransferase AtTSM1 specifically to the tapetum of young flower
      buds enabled the subsequent identification of several genes with a putative role
      in phenylpropanoid polyamine conjugate biosynthesis. Based on the analysis of
      several A. thaliana knockout mutants, a biosynthetic pathway of these conjugates
      is proposed, which involves two methylation steps catalyzed by different cation
      dependent O-methyltransferases, a cytochrome P450 (CYP98A8) catalyzed
      hydroxylation, and a conjugating acyl transfer performed by a BAHD-like,
      hydroxycinnamoyl (HC)-transferase. LC/MS based metabolite profiling of the
      cyp98A8 knockout line identified new feruloyl- and 4-coumaroylspermidine
      conjugates in the corresponding flowers consistent with a role of this gene in
      the hydroxylation of these conjugates. A pattern of minor amounts of bis- and
      tris-acylspermidine conjugates, likely the products of additional HC-transferases
      were identified in wild type as well as in the mutant lines. Transcript
      suppression of the genes early in the pathway was observed in knockout or RNAi
      lines of the genes encoding late enzymatic steps. The implication of these
      findings for spermidine conjugate biosynthesis in flower buds of A. thaliana is
      discussed.

PMID- 19762056
TI  - [Is there a bridge between migraine and familial mesial temporal lobe epilepsy?].
AB  - Numerous reviews have emphasized the links between certain types of epilepsy and
      migraine. Historically, Gowers was one of the first, in 1907, to have drawn
      attention to a possible relationship between migraine headache and epilepsy in a
      period when no additional examination was available. In the last two decades,
      progress in molecular biology, electrophysiology, and neuro-imaging has enabled a
      better approach to the fundamental elements underlying the interrelationship
      between these two nosological domains. During this same time, a new term
      "channelopathy" has appeared in the literature. This term groups together
      affections involving a dysfunction of ion channels. In this article, the links
      between the different types of migraine and familial mesial temporal lobe
      epilepsy are illustrated by two case reports. This association does not appear to
      occur at random but would undoubtedly depend on a common genetic substratum,
      leading to a direct comorbidity. These occasional recurring symptoms would lie
      within the framework of a more general concept of "Primary Brain
      Channelopathies".

PMID- 19762057
TI  - Scrub typhus mimicking enteric fever; a report of three patients.
AB  - We report three patients who presented with fever and late onset diarrhoea
      mimicking enteric fever. All three patients were diagnosed with an Orientia
      tsutsugamushi infection and responded dramatically to doxycycline treatment.
      Clinicians practicing in rickettsial disease endemic areas should be made aware
      of similar clinical presentations in order to prevent morbidity and mortality
      associated with rickettsioses.

PMID- 19762058
TI  - Wash resistance and residual efficacy of long-lasting polyester netting coated
      with alpha-cypermethrin (Interceptor) against malaria-transmitting mosquitoes in
      Assam, northeast India.
AB  - Malaria is endemic in Assam, northeast India, with low-to-moderate transmission
      of the causative parasites, mostly by Anopheles minimus. Plasmodium falciparum is
      the predominant parasite (>60%), with remaining cases being due to P. vivax. As
      an alternative intervention for malaria control, long-lasting insecticidal nets
      [Interceptor coated with alpha-cypermethrin 10% suspension concentrate (SC),
      0.667% w/w, 0.2g/m(2)] underwent field evaluation for laboratory wash resistance
      and residual efficacy in field conditions against malaria-transmitting
      mosquitoes. Based on entomological observations, the Interceptor net intervention
      was the most effective, corresponding to the lowest mosquito vector density in
      experimental villages. There was virtual disappearance of A. minimus in
      Interceptor net villages in contrast to the untreated net intervention and the no
      net control. Contact cone bioassay tests revealed 100% mortality in the A.minimus
      group of mosquito species in the community using the Interceptor net, which was
      consistent during the follow-up monitoring period (October 2006 to April 2007) in
      field conditions. Similar levels of mortality were observed in laboratory-washed
      nets compared with unwashed nets, and wash resistance was consistent even after
      the 20th serial wash at fortnightly intervals. Community compliance and
      acceptance of the Interceptor net was high, with decreased nuisance due to biting
      mosquitoes and other household insect pests being reported.

PMID- 19762059
TI  - Nanocomposite cerium oxide polymer matching layers with adjustable acoustic
      impedance between 4 MRayl and 7 MRayl.
AB  - A new class of materials for ultrasonic matching layers is presented. The
      materials consist of nanoscale cerium oxide particles in an epoxy functionalized
      organic inorganic hybrid polymer matrix. The cerium oxide agglomerates to
      particles with 20 nm diameters. The content of particles in the polymer matrix
      could be increased to 75 wt.% which corresponds to 37 vol.%. The most technical
      important piezoelectrical ceramics have an acoustic impedance of about 30 MRayl,
      to improve coupling into water or biological tissue with an acoustic impedance of
      about 1.5 MRayl a matching layer should have an acoustic impedance of about 6.8
      MRayl. With a filling degree of 75 wt.% the new composite material reaches an
      acoustic impedance of 7 MRayl. The materials are synthesized by a hydrolytic
      condensation combined with polymerization. This way of synthesis allows the use
      of organic solvents to adjust the viscosity of the sol and the application of
      different coating techniques. Ultrasound transducers (100 MHz) were built to test
      the new matching layers and an increase of the voltage signal amplitude of about
      100% could be detected.

PMID- 19762061
TI  - Comparison of the action spectra and relative DNA absorbance spectra of
      microorganisms: information important for the determination of germicidal fluence
      (UV dose) in an ultraviolet disinfection of water.
AB  - The action spectra of Bacillus subtilis spores (ATCC6633) and Salmonella
      typhimurium LT2 were characterized using physical radiometry for irradiance
      measurements and a multiple target model to interpret the inactivation kinetics.
      The observed action spectrum of B. subtilis spores deviated significantly from
      the relative absorbance spectrum of the DNA purified from the spores, but matched
      quite well with the relative absorbance spectrum of decoated spores. The action
      spectrum of B. subtilis spores determined in this study was statistically
      different from those reported in previous studies. On the other hand, the action
      spectrum of S. typhimurium bacteria matched quite well with the relative
      absorbance spectrum of DNA extracted from vegetative cells, except in the region
      below 240nm. It is concluded that the common use of the relative DNA absorbance
      spectrum as a surrogate for the germicidal action spectrum can result in
      systematic errors when evaluating the performance of a polychromatic UV light
      reactors using bioassays. For example, if the weighted germicidal fluence (UV
      dose) calculated using the relative DNA absorbance spectrum as the germicidal
      weighting factor is found to be 40mJcm(-2) for a medium pressure lamp UV reactor,
      that calculated using the relative action spectrum of B. subtilis spores, as
      determined in this study, would be 66mJcm(-2).

PMID- 19762060
TI  - Select resistance-associated mutations in blood are associated with lower CSF
      viral loads and better neuropsychological performance.
AB  - BACKGROUND: When antiretroviral therapy does not fully suppress HIV replication,
      suboptimal levels of antiretrovirals can select for antiretroviral resistant
      variants of HIV. These variants may exhibit reduced replication capacity and
      result in lower viral loads in blood. Our study evaluated whether antiretroviral
      resistance was associated with viral loads in the cerebrospinal fluid (CSF) and
      better neuropsychological (NP) performance. METHODS: We enrolled 94 participants
      and each participant underwent a comprehensive neuromedical evaluation that used
      structured clinical assessments of medical history, ART and other medication use,
      comprehensive NP testing, and neurological and general physical signs of disease.
      Blood was collected by venipuncture, and all participants were offered lumbar
      puncture. Univariate and multivariate statistical methods were used to analyze
      the relationship between antiretroviral resistance, blood and CSF HIV RNA levels,
      substance use, and NP performance. RESULTS: Antiretroviral resistance, detected
      in blood, was associated with lower CSF viral loads (p<0.01) and better NP
      performance (p=0.04) in multivariate analyses, independent of past and current
      ARV use and blood viral loads (model: p<0.01). However, HIV RNA levels in CSF did
      not independently correlate with NP performance. Low viral loads in the CSF
      limited our ability to investigate the relationship between antiretroviral
      resistance detected in CSF and NP performance. CONCLUSIONS: Even in the absence
      of ART, antiretroviral resistance-associated mutations correlate with better NP
      performance possibly because these mutations reflect reduced neurovirulence
      compared with wild-type HIV.

PMID- 19762062
TI  - Storm water runoff measurements of copper from a naturally patinated roof and
      from a parking space. Aspects on environmental fate and chemical speciation.
AB  - Release of copper from a naturally aged copper roof on a shopping centre building
      in a suburban site of Stockholm has been measured during different rain events
      after its interaction with the internal drainage system and storm drains made of
      cast iron and concrete. Concentrations of copper removed by means of urban storm
      water from a nearby parking space have been determined for comparison.
      Predictions and measurements of the chemical speciation of released copper are
      discussed compared to the total concentration, and to threshold values for
      freshwater and drinking water. The results clearly illustrate that the major part
      of the released copper from the roof is readily retained already during transport
      through the internal drainage system of the building, a pathway that also changes
      the chemical speciation of released copper and its bioavailable fraction. Most
      copper, not retained by cast iron and concrete surfaces, was strongly complexed
      to organic matter. The median concentration of free cupric ions and weak copper
      complexes was less than, or within the range of reported no effect
      concentrations, NOECs, of copper in surface waters. The parking space contributed
      with significantly higher and time-dependent concentrations of total copper
      compared to measured concentrations of copper from the roof after the interaction
      with the drainage system. Most copper in the surface runoff water was strongly
      complexed with organic matter, hence reducing the bioavailable fraction
      significantly to concentrations within the NOEC range. Dilution with other
      sources of urban storm water will reduce the released concentration of copper
      even further. The results illustrate that already the internal drainage system
      and the storm drains made of cast iron and concrete act as efficient sinks for
      released copper which means that any installation of additional infiltration
      devices is redundant.

PMID- 19762063
TI  - Use of static Quantitative Microbial Risk Assessment to determine pathogen risks
      in an unconfined carbonate aquifer used for Managed Aquifer Recharge.
AB  - Managed Aquifer Recharge (MAR) is becoming a mechanism used for recycling treated
      wastewater and captured urban stormwater and is being used as a treatment barrier
      to remove contaminants such as pathogens from the recharged water. There is still
      a need, however, to demonstrate the effectiveness of MAR to reduce any residual
      risk of pathogens in the recovered water. A MAR research site recharging
      secondary treated wastewater in an unconfined carbonate aquifer was used in
      conjunction with a static Quantitative Microbial Risk Assessment (QMRA) to assess
      the microbial pathogen risk in the recovered water following infiltration and
      aquifer passage. The research involved undertaking a detailed hydrogeological
      assessment of the aquifer at the MAR site and determining the decay rates of
      reference pathogens from an in-situ decay study. These variables along with
      literature data were then used in the static QMRA which demonstrated that the
      recovered water at this site did not meet the Australian Guidelines for recycled
      water when used for differing private green space irrigation scenarios. The
      results also confirmed the importance of obtaining local hydrogeological data as
      local heterogeneity can influence of residence time in the aquifer which, in
      turn, influences the outcomes. The research demonstrated that a static QMRA can
      be used to determine the residual risk from pathogens in recovered water and
      showed that it can be a valuable tool in the preliminary design and operation of
      MAR systems and the incorporation of complementary engineered treatment processes
      to ensure that there is acceptable health risk from the recovered water.

PMID- 19762064
TI  - Quantitative structure - photodegradation relationships of polybrominated
      diphenyl ethers, phenoxyphenols and selected organochlorines.
AB  - Among other developments, the technological revolution has lead to introduction
      of new chemicals to better serve in instruments and materials. The consequences
      of the extensive increase in use of new chemicals can be detected in the
      environment world wide, i.e. in wildlife and humans. To ensure this problem to be
      minimised in the future, new chemicals need to be subjected to predictive
      assessments before commercialised. To facilitate screening, qualitative structure
      activity relationships, quantitative structure-activity relationships may be
      applied to describe reactivity of chemicals. Physico-chemical properties of
      chemicals such as partition coefficients and half-lives for the various
      environmental compartments are essential input data in multimedia environmental
      fate models. In this study we examine how structural characteristics can
      quantitatively describe laboratory determined photolytic half-lives of
      halogenated compounds of different classes, such as polybrominated diphenyl
      ethers (PBDEs), hydroxylated brominated diphenyl ethers (OH-PBDEs), and other
      organohalogens. A total of 30 chemicals with experimentally measured half-lives
      are used. Results reveal that the most important descriptors for describing the
      half-lives of the brominated compounds are the energy gap (GAP-1) between HOMO-1
      and LUMO, the lowest partial charge on a halogen atom (Qhal-), topological polar
      surface area (TPSA), the atom with highest radical superdelocalizability (Rad
      super+) and LUMO density (LUMO+).

PMID- 19762065
TI  - Impact of American Society of Clinical Oncology/College of American Pathologists
      guideline recommendations on HER2 interpretation in breast cancer.
AB  - Accurate assessment of human epidermal growth factor receptor 2 is critical for
      the management of patients with breast cancer. We set out to study the impact of
      the 2007 American Society of Clinical Oncology/College of American Pathologists
      guidelines on the interpretation of human epidermal growth factor receptor 2 IHC
      results and its correlation with fluorescence in situ hybridization results.
      Invasive breast carcinomas with IHC HercepTest 3+ were retrieved from the archive
      of Mayo Clinic Rochester. The human epidermal growth factor receptor 2 slides
      were rereviewed, and results were recorded as percentage of invasive tumor cells
      with 3+, 2+, 1+, and 0 staining intensity. Human epidermal growth factor receptor
      2 gene amplification by fluorescence in situ hybridization was performed on all
      tumors with 3+ staining in 70% or less of tumor cells. Of the 141 cases studied,
      12 cases showed intense membrane staining in 11% to 30% of the invasive tumor
      cells and would have been scored as 2+ according to the new American Society of
      Clinical Oncology/College of American Pathologists guidelines. Of these 12 cases,
      6 were positive for human epidermal growth factor receptor 2 gene amplification
      by fluorescence in situ hybridization (ratio >2.2), 4 cases were negative
      (HER2/CEP17 ratio of < 1.8), and 2 cases were equivocal (ratio of 1.8-2.2). One
      human epidermal growth factor receptor 2-positive case showed dramatic
      intratumoral heterogeneity with high-level amplification (ratio of 12.2) in the
      IHC 3+ area and no amplification (ratio of 1.0) in the IHC 1+/2+ areas. The 2007
      American Society of Clinical Oncology/College of American Pathologists guidelines
      down-scored 2.8% of tumors from human epidermal growth factor receptor 2-positive
      (IHC 3+) to human epidermal growth factor receptor 2-negative (IHC 2+ equivocal
      and fluorescence in situ hybridization negative) in this study. Clinical studies
      are needed to determine whether the updated guidelines are better at predicting
      response to anti-human epidermal growth factor receptor 2 therapy.

PMID- 19762066
TI  - Clinicopathologic correlation of beclin-1 and bcl-2 expression in human breast
      cancer.
AB  - The human beclin-1 gene, located on chromosome 17q21, has been identified as the
      mammalian orthologue of Atg6 (autophagy-related gene) and may be a
      haploinsufficient tumor suppressor gene. The function and expression of beclin-1
      in human breast cancer are largely unknown. We investigated the expression of
      beclin-1 and bcl-2 in human breast cancer. Tissue samples from 125 cases of
      invasive breast cancer were used for the present study. Immunohistochemical
      staining for beclin-1 and bcl-2 was evaluated using tissue microarray, then the 2
      proteins were correlated with clinicopathologic parameters. Positive beclin-1
      expression and bcl-2 expression in breast cancer tissue were observed in 53 cases
      (42.4%) and 48 cases (38.4%), respectively. Beclin-1 expression was inversely
      correlated with bcl-2 expression in breast cancer tissue (P = .035). Beclin-1
      expression significantly correlated with nuclear pleomorphism and mitotic count.
      Bcl-2 expression in breast cancer tissue significantly correlated with histologic
      grade, tubule formation, nuclear pleomorphism, mitotic count, estrogen receptor,
      and distant metastasis. Our results suggest that beclin-1 might play a role in
      the inhibition of the development of breast cancer and that inhibition might be
      due to an interaction with bcl-2 protein.

PMID- 19762067
TI  - Urothelial dysplasia and other flat lesions of the urinary bladder:
      clinicopathologic and molecular features.
AB  - The 2004 World Health Organization classification system for urothelial neoplasia
      classifies flat-related preneoplastic lesions as urothelial hyperplasia (flat and
      papillary), reactive urothelial atypia, urothelial atypia of unknown
      significance, urothelial dysplasia (low-grade intraurothelial neoplasia), and
      urothelial carcinoma in situ (high-grade intraurothelial neoplasia). Each lesion
      is defined with precise nomenclature and strict morphologic criteria. In many
      cases, morphologic features alone suffice for diagnosis. Other cases may require
      a panel of immunohistochemical antibodies consisting of cytokeratin 20, p53, and
      CD44 for diagnosis. Recent molecular studies have provided further insight into
      the premalignant potential of these urothelial lesions. Herein, we present a
      review of flat urothelial lesions of the urinary bladder as defined by the 2004
      World Health Organization classification with focus on the clinicopathologic,
      immunohistochemical, and molecular features.

PMID- 19762068
TI  - Estrogen receptor immunohistochemistry cutoff value: standardization is needed.

PMID- 19762069
TI  - Drug reaction with eosinophilia and systemic symptoms: a cause of human
      herpesvirus 6-related fulminant myocarditis and hepatitis in immunocompetent
      patients.

PMID- 19762070
TI  - Cladistic analyses of behavioural variation in wild Pan troglodytes: exploring
      the chimpanzee culture hypothesis.
AB  - Long-term field studies have revealed considerable behavioural differences among
      groups of wild Pan troglodytes. Here, we report three sets of cladistic analyses
      that were designed to shed light on issues relating to this interpopulation
      variation that are of particular relevance to palaeoanthropology. In the first
      set of analyses, we focused on the proximate cause of the variation. Some
      researchers have argued that it is cultural, while others have suggested that it
      is the result of genetic differences. Because the eastern and western subspecies
      of P. troglodytes are well differentiated genetically while groups within the
      subspecies are not, we reasoned that if the genetic hypothesis is correct, the
      phylogenetic signal should be stronger when data from the eastern and western
      subspecies are analysed together compared to when data from only the eastern
      subspecies are analysed. Using randomisation procedures, we found that the
      phylogenetic signal was substantially stronger with in a single subspecies rather
      than with two. The results of the first sets of analyses, therefore, were
      inconsistent with the predictions of the genetic hypothesis. The other two sets
      of analyses built on the results of the first and assumed that the intergroup
      behavioural variation is cultural in nature. Recent work has shown that, contrary
      to what anthropologists and archaeologists have long believed, vertical
      intergroup transmission is often more important than horizontal intergroup
      transmission in human cultural evolution. In the second set of analyses, we
      sought to determine how important vertical transmission has been in the evolution
      of chimpanzee cultural diversity. The first analysis we carried out indicated
      that the intergroup similarities and differences in behaviour are consistent with
      the divergence of the western and eastern subspecies, which is what would be
      expected if vertical intergroup transmission has been the dominant process. In
      the second analysis, we found that the chimpanzee cultural data are not only
      comparable to a series of modern human cultural data sets in terms of how tree
      like they are, but are also comparable to a series of genetic, anatomical, and
      behavioural data sets that can be assumed to have been produced by a branching
      process. Again, this is what would be expected if vertical inter-group
      transmission has been the dominant process in chimpanzee cultural evolution.
      Human culture has long been considered to be adaptive, but recent studies have
      suggested that this needs to be demonstrated rather than assumed. With this in
      mind, in the third set of analyses we investigated whether chimpanzee culture is
      adaptive. We found the hypothesis that chimpanzee culture is adaptive was
      supported by an analysis of data from the Eastern African subspecies, but not by
      an analysis of data from the eastern and western subspecies. The results of our
      analyses have implications for the number of subspecies in Pan troglodytes, the
      relationship between hominin taxa and Palaeolithic industries, and the evolution
      of hominin cognition and behaviour.

PMID- 19762071
TI  - Effects of carvedilol or metoprolol on PAI-1, tPA-mass concentration or Von
      Willebrand factor in chronic heart failure--a COMET substudy.
AB  - INTRODUCTION: In COMET (Carvedilol or Metoprolol European Trial), carvedilol
      reduced mortality compared with metoprolol in patients with chronic heart
      failure. We hypothesized that carvedilol might have greater effects on
      endothelial derived haemostatic factors than metoprolol. We aimed to study the
      effects of carvedilol or metoprolol on tissue plasminogen activator (tPA), its
      inhibitor PAI-1 and Von Willebrand factor (VWF) in patients with heart failure.
      MATERIAL AND METHODS: We recruited 260 patients (134 on carvedilol, 126 on
      metoprolol), mean age 66 years and 84% of them men. Plasma mass concentrations of
      tPA and PAI-1and percent of VWF were measured at baseline and after one and two
      years of treatment. RESULTS: Plasma tPA, PAI-1 and VWF were similar between
      treatment groups at baseline and no significant differences between groups
      emerged after one or two years of treatment. In paired analyses in patients
      assigned to carvedilol, median PAI-1 level decreased from 37.2 to 32.1 microg/l
      at two years (p=0.034) and of VWF decreased from baseline to one year (240 vs.
      218%, p=0.023) in patients assigned to carvedilol but were not reduced at any
      time in patients assigned to metoprolol. Plasma tPA increased over time in both
      treatment groups (p=0.013 and 0.027 respectively). CONCLUSION: We found no
      significant difference in the effects of carvedilol or metoprolol on tPA, PAI-1
      and VWF. Comparison over time within treatment groups suggested that PAI-1 and
      VWF might have declined on carvedilol but not on metoprolol. Our hypothesis is
      not proved but this may reflect an inadequate sample size rather than lack of an
      effect.

PMID- 19762072
TI  - Photobleaching of camphorquinone during polymerization of dimethacrylate-based
      resins.
AB  - OBJECTIVE: The aim of this study was to compare the photobleaching rate of CQ in
      different dental resins. METHODS: The photodecomposition rate of CQ/amine system
      in bis-GMA/TEGDMA, bis-EMA and UDMA polymerizing monomers was evaluated at
      different light intensities. The photobleaching of the CQ was studied by
      monitoring the decrease in light absorption as a function of continuous
      irradiation time. The absorption changes were assessed by recording the
      transmitted light that passed through samples of monomers containing CQ/amine.
      RESULTS: Complete photobleaching of CQ was observed in all the monomer tested and
      the rate constant for the photobleaching was proportional to the radiation
      intensity. Hydrogen abstraction from amines by the excited CQ state via electron
      transfer and direct hydrogen abstraction from monomer structures were involved in
      the CQ photoreduction. CQ was photobleached in the absence of coinitiator in a
      dimethacrylate monomer containing a carbamate functional group (UDMA). This
      behavior was attributed to the presence of labile hydrogen atoms in the UDMA
      monomer. The CQ photobleaching rate constant in UDMA containing CQ/amine was
      similar to that in UDMA in the absence of amine. Moreover, the efficiency of CQ
      to photoinitiate the polymerization of UDMA in the absence of amine demonstrated
      that the radicals derived from the UDMA monomer via hydrogen abstraction are
      highly reactive toward double bonds. SIGNIFICANCE: CQ photoinitiates the
      polymerization of the UDMA monomer in the absence of amine and the efficiency of
      this process is comparable to that of traditional bis-GMA and bis-EMA monomers
      activated with CQ/amine.

PMID- 19762073
TI  - Exploring the relevance of expressed emotion to the treatment of social anxiety
      disorder in adolescence.
AB  - The role that the involvement of parents may play in the treatment outcome of
      their children with anxiety disorders is still under debate. Some studies dealing
      with other disorders have examined the role that the expressed emotion (EE)
      construct (parental overinvolvement, criticism and hostility) may play in
      treatment outcome and relapse. Given that some of these aspects have been
      associated with social anxiety for a long time, it was hypothesized that EE may
      be associated with lower treatment outcome. The sample was composed of 16
      adolescents who benefited from a school-based, cognitive-behavioural intervention
      aimed at overcoming social anxiety. Then, parents were classified with high or
      low EE. The results revealed that the adolescents whose parents had low EE showed
      a statistically significant reduction of their social anxiety scores at posttest,
      as opposed to adolescents of parents with high expressed emotion. These findings
      suggest that parental psychopathology (parents with high EE) should be taken into
      consideration to prevent poor adolescent treatment outcome.

PMID- 19762074
TI  - Will CESAR answer the adult ECMO debate?

PMID- 19762076
TI  - Politicians must heed health effects of climate change.

PMID- 19762077
TI  - Health and climate change.

PMID- 19762078
TI  - The relative roles of collagen adhesive receptor DDR2 activation and matrix
      stiffness on the downregulation of focal adhesion kinase in vascular smooth
      muscle cells.
AB  - Cells within tissues derive mechanical anchorage and specific molecular signals
      from the insoluble extracellular matrix (ECM) that surrounds them. Understanding
      the role of different cues that extracellular matrices provide cells is critical
      for controlling and predicting cell response to scaffolding materials. Using an
      engineered extracellular matrix of Type I collagen we examined how the stiffness,
      supramolecular structure, and glycosylation of collagen matrices influence the
      protein levels of cellular FAK and the activation of myosin II. Our results show
      that (1) cellular FAK is downregulated on collagen fibrils, but not on a non
      fibrillar monolayer of collagen, (2) the downregulation of FAK is independent of
      the stiffness of the collagen fibrils, and (3) FAK levels are correlated with
      levels of tyrosine phosphorylation of the collagen adhesion receptor DDR2.
      Further, siRNA depletion of DDR2 blocks FAK downregulation. Our results suggest
      that the collagen receptor DDR2 is involved in the regulation of FAK levels in
      vSMC adhered to Type I collagen matrices, and that regulation of FAK levels in
      these cells appears to be independent of matrix stiffness.

PMID- 19762079
TI  - The effects of rhBMP-2 released from biodegradable polyurethane/microsphere
      composite scaffolds on new bone formation in rat femora.
AB  - Scaffolds prepared from biodegradable polyurethanes (PUR) have been investigated
      as a supportive matrix and delivery system for skin, cardiovascular, and bone
      tissue engineering. While previous studies have suggested that PUR scaffolds are
      biocompatible and moderately osteoconductive, the effects of encapsulated
      osteoinductive molecules, such as recombinant human bone morphogenetic protein
      (rhBMP-2), on new bone formation have not been investigated for this class of
      biomaterials. The objective of this study was to investigate the effects of
      different rhBMP-2 release strategies on new bone formation in PUR scaffolds
      implanted in rat femoral plug defects. In the simplest approach, rhBMP-2 was
      added as a dry powder prior to the foaming reaction, which resulted in a burst
      release of 35% followed by a sustained release for 21 days. Encapsulation of
      rhBMP-2 in either 1.3-micron or 114-micron PLGA microspheres prior to the foaming
      reaction reduced the burst release. At 4 weeks post-implantation, all rhBMP-2
      treatment groups enhanced new bone formation relative to the scaffolds without
      rhBMP-2. Scaffolds incorporating rhBMP-2 powder promoted the most extensive new
      bone formation, while scaffolds incorporating rhBMP-2 encapsulated in 1.3-micron
      microspheres, which exhibited the lowest burst release, promoted the least
      extensive new bone formation. Thus our observations suggest that an initial burst
      release followed by sustained release is better for promoting new bone formation.

PMID- 19762075
TI  - Efficacy and economic assessment of conventional ventilatory support versus
      extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR):
      a multicentre randomised controlled trial.
AB  - BACKGROUND: Severe acute respiratory failure in adults causes high mortality
      despite improvements in ventilation techniques and other treatments (eg,
      steroids, prone positioning, bronchoscopy, and inhaled nitric oxide). We aimed to
      delineate the safety, clinical efficacy, and cost-effectiveness of extracorporeal
      membrane oxygenation (ECMO) compared with conventional ventilation support.
      METHODS: In this UK-based multicentre trial, we used an independent central
      randomisation service to randomly assign 180 adults in a 1:1 ratio to receive
      continued conventional management or referral to consideration for treatment by
      ECMO. Eligible patients were aged 18-65 years and had severe (Murray score >3.0
      or pH <7.20) but potentially reversible respiratory failure. Exclusion criteria
      were: high pressure (>30 cm H(2)O of peak inspiratory pressure) or high FiO(2)
      (>0.8) ventilation for more than 7 days; intracranial bleeding; any other
      contraindication to limited heparinisation; or any contraindication to
      continuation of active treatment. The primary outcome was death or severe
      disability at 6 months after randomisation or before discharge from hospital.
      Primary analysis was by intention to treat. Only researchers who did the 6-month
      follow-up were masked to treatment assignment. Data about resource use and
      economic outcomes (quality-adjusted life-years) were collected. Studies of the
      key cost generating events were undertaken, and we did analyses of cost-utility
      at 6 months after randomisation and modelled lifetime cost-utility. This study is
      registered, number ISRCTN47279827. FINDINGS: 766 patients were screened; 180 were
      enrolled and randomly allocated to consideration for treatment by ECMO (n=90
      patients) or to receive conventional management (n=90). 68 (75%) patients
      actually received ECMO; 63% (57/90) of patients allocated to consideration for
      treatment by ECMO survived to 6 months without disability compared with 47%
      (41/87) of those allocated to conventional management (relative risk 0.69; 95% CI
      0.05-0.97, p=0.03). Referral to consideration for treatment by ECMO led to a gain
      of 0.03 quality-adjusted life-years (QALYs) at 6-month follow-up [corrected]. A
      lifetime model predicted the cost per QALY of ECMO to be pound19 252 (95% CI 7622
      59 200) at a discount rate of 3.5%. INTERPRETATION: We recommend transferring of
      adult patients with severe but potentially reversible respiratory failure, whose
      Murray score exceeds 3.0 or who have a pH of less than 7.20 on optimum
      conventional management, to a centre with an ECMO-based management protocol to
      significantly improve survival without severe disability. This strategy is also
      likely to be cost effective in settings with similar services to those in the UK.
      FUNDING: UK NHS Health Technology Assessment, English National Specialist
      Commissioning Advisory Group, Scottish Department of Health, and Welsh Department
      of Health.

PMID- 19762080
TI  - The expression of connective tissue growth factor in pregnancies complicated by
      severe preeclampsia or fetal growth restriction.
AB  - We tested the hypothesis that the expression of placental connective tissue
      growth factor (CTGF) is enhanced in pregnancies complicated by severe
      preeclampsia (PE) or fetal growth restriction (FGR). CTGF expression was analyzed
      using immunostaining, western blot and real-time quantitative PCR in placental
      samples obtained after third trimester cesarean deliveries without labor from
      women with severe PE (n=11), idiopathic FGR (n=14), or healthy controls (n=14).
      Serum CTGF concentrations were analyzed using ELISA. We found that CTGF was
      stably expressed in villous trophoblasts throughout pregnancy. The expression of
      CTGF mRNA in placentas from severe PE or FGR was higher than placentas from
      controls. Whereas the levels of placental CTGF protein were similar between
      normal and severe PE, maternal and fetal serum CTGF levels were elevated in
      severe PE. Maternal CTGF levels were also distinctively elevated in women with PE
      or FGR with histological evidence of placental injury. The enhancement of CTGF
      expression as well as serum CTGF levels in clinical conditions attributed to
      placental dysfunction suggests a role for this secretary protein in the
      pathophysiology of placental injury or its sequelae.

PMID- 19762081
TI  - Histone deacetylase inhibitors: a new perspective for the treatment of leukemia.
AB  - Histone deacetylase inhibitors (HDIs) promote or enhance several different
      anticancer mechanisms and therefore are in evidence as potential antileukemia
      agents. Studies on leukemia have provided examples for their functional
      implications in cancer development and progression, as well as their relevance
      for therapeutic targeting. A number of HDIs have been tested in clinical trials
      and have been proven safe with significant clinical activity. The use of HDIs in
      association with other molecules, such as classical chemotherapeutic drugs and
      DNA demethylating agents, has been implied as a promising treatment alternative
      for leukemia patients in the future. Here we describe the histone deacetylase
      inhibitors that have been tested in clinical trials for the treatment of leukemia
      and lymphoma. We conclude that further clinical trials involving a broader number
      of HDIs used either alone or in combination with other agents are needed to
      consolidate the use of these epigenetic modulators on leukemia therapy.

PMID- 19762082
TI  - Interleukin-6 leads to interleukin-10 production in several human multiple
      myeloma cell lines. Does interleukin-10 enhance the proliferation of these cells?
AB  - Multiple myeloma (MM) is characterised as a malignant plasma cell proliferation.
      Interleukin-6 (IL-6) is an important cytokine in the proliferation of the
      multiple myeloma cells. Interleukin-10 (IL-10) is involved in the terminal
      differentiation of B cells into plasma cells and enhances the proliferation of B
      cells. Elevated IL-10 levels were detected in patients with MM, relating to the
      clinical manifestation of the disease. In this study it was investigated the
      effect of exogenous IL-6 on the IL-10 production and the proliferative effect of
      IL-6 and IL-10 in human multiple myeloma cell lines. The ten cell lines had
      different sources: blood, ascitic fluid, bone marrow, peritoneum and lymph node.
      RESULTS: (1) Four cell lines produced IL-10 (up to 179 pg/ml) spontaneously. IL-6
      increased the IL-10 production up to 1626 pg/ml in 6/10 cell lines. With IL-6
      receptor antagonist (IL-6RA) the values of IL-10 were in the range of untreated
      samples (spontaneous cytokine production). IL-6RA counteracted the increased IL
      10 production induced by IL-6 treatment and decreased the high values of IL-10
      significantly. (2) IL-6 enhanced the proliferation (up to 160%) in 9/10 cell
      lines, IL-10 enhanced the proliferation (up to 170%) in 7/10 cell lines. There
      was a significant correlation between the proliferative effects of IL-6 and IL
      10. CONCLUSION: It is reported for the first time that IL-6 leads to a marked
      production of IL-10 and that this cytokine is an IL-6 related growth factor for
      MM cells. The findings of this study can be important in the therapeutic
      modalities of multiple myeloma.

PMID- 19762083
TI  - The suggestion of a risk stratification system for febrile neutropenia in
      patients with hematologic disease.
AB  - We analyzed the prognostic factors from 259 cases of febrile neutropenia
      occurring in 137 patients with hematologic disease. Based on multivariate
      analysis, significant prognostic factors are recovery of neutropenia, respiratory
      infection, baseline serum albumin, baseline bicarbonate, baseline CRP, and CRP on
      the fifth day after antibiotic treatment. From these variables, we derived a
      predictive model for the prognosis of febrile neutropenia using baseline serum
      albumin, bicarbonate, and CRP, which could be easily checked before chemotherapy.
      Further studies in prospective setting are needed for the validation of this
      model.

PMID- 19762084
TI  - Prevalence of amblyopia and strabismus in white and African American children
      aged 6 through 71 months the Baltimore Pediatric Eye Disease Study.
AB  - OBJECTIVE: To determine the age-specific prevalence of strabismus in white and
      African American children aged 6 through 71 months and of amblyopia in white and
      African American children aged 30 through 71 months. DESIGN: Cross-sectional,
      population-based study. PARTICIPANTS: White and African American children aged 6
      through 71 months in Baltimore, MD, United States. Among 4132 children
      identified, 3990 eligible children (97%) were enrolled and 2546 children (62%)
      were examined. METHODS: Parents or guardians of eligible participants underwent
      an in-home interview and were scheduled for a detailed eye examination, including
      optotype visual acuity and measurement of ocular deviations. Strabismus was
      defined as a heterotropia at near or distance fixation. Amblyopia was assessed in
      those children aged 30 through 71 months who were able to perform optotype
      testing at 3 meters. MAIN OUTCOME MEASURES: The proportions of children aged 6
      through 71 months with strabismus and of children aged 30 through 71 months with
      amblyopia. RESULTS: Manifest strabismus was found in 3.3% of white and 2.1% of
      African American children (relative prevalence [RP], 1.61; 95% confidence
      interval [CI], 0.97-2.66). Esotropia and exotropia each accounted for close to
      half of all strabismus in both groups. Only 1 case of strabismus was found among
      84 white children 6 through 11 months of age. Rates were higher in children 60
      through 71 months of age (5.8% for whites and 2.9% for African Americans [RP,
      2.05; 95% CI, 0.79-5.27]). Amblyopia was present in 12 (1.8%) white and 7 (0.8%)
      African American children (RP, 2.23; 95% CI, 0.88-5.62). Only 1 child had
      bilateral amblyopia. CONCLUSIONS: Manifest strabismus affected 1 in 30 white and
      1 in 47 African American preschool-aged children. The prevalence of amblyopia was
      <2% in both whites and African Americans. National population projections suggest
      that there are approximately 677,000 cases of manifest strabismus among children
      6 through 71 months of age and 271 000 cases of amblyopia among children 30
      through 71 months of age in the United States.

PMID- 19762085
TI  - Epidemiology and symptomatology of depression in Sri Lanka: a cross-sectional
      population-based survey in Colombo District.
AB  - BACKGROUND: It is important to understand the nature of depression in non-Western
      and lower-income countries, but little such research exists. This study aimed to
      examine the characteristic features of depression in Sri Lanka, and to identify
      environmental risk factors. METHODS: Depression diagnoses, symptoms and
      impairment were measured using the Composite International Diagnostic Interview,
      in a population-based sample of 6014 twins and non-twins in the Colombo region of
      Sri Lanka (the CoTASS sample). Socio-demographic factors and environments were
      assessed via questionnaires. RESULTS: Lifetime-ever depression was reported in
      6.6% of participants, rising to 11.2% if the functional impairment criterion was
      excluded. The symptom profile of depression and its socio-demographic
      associations were very comparable to those in Western and more economically
      developed countries, whether functional impairment was included in the definition
      or not. Standard of living was independently associated with depression,
      especially among men at the more deprived end of the distribution. Specific
      associations were found with both financial wellbeing and material
      characteristics of the home environment. LIMITATIONS: The observational
      associations identified are cross-sectional, so do not necessarily imply causal
      links. CONCLUSIONS: Aside from a lower prevalence, depression is very similar in
      this predominantly urban Sri Lankan sample to higher-income, Western countries,
      and may be under-identified due to a relatively low cultural appropriateness of
      the assessment of impairment. Under Sri Lanka's cultural and environmental
      context, certain aspects of the material environment are associated with
      depression among certain segments of society, perhaps because of their particular
      link to social status and social networks.

PMID- 19762086
TI  - Abnormal externally guided movement preparation in recent-onset schizophrenia is
      associated with impaired selective attention to external input.
AB  - Several theories propose that the primary cognitive impairment in schizophrenia
      concerns a deficit in the processing of external input information. There is also
      evidence, however, for impaired motor preparation in schizophrenia. This provokes
      the question whether the impaired motor preparation in schizophrenia is a
      secondary consequence of disturbed (selective) processing of the input needed for
      that preparation, or an independent primary deficit. The aim of the present study
      was to discriminate between these hypotheses, by investigating externally guided
      movement preparation in relation to selective stimulus processing. The sample
      comprised 16 recent-onset schizophrenia patients and 16 controls who performed a
      movement-precuing task. In this task, a precue delivered information about one,
      two or no parameters of a movement summoned by a subsequent stimulus. Performance
      measures and measures derived from the electroencephalogram showed that patients
      yielded smaller benefits from the precues and showed less cue-based preparatory
      activity in advance of the imperative stimulus than the controls, suggesting a
      response preparation deficit. However, patients also showed less activity
      reflecting selective attention to the precue. We therefore conclude that the
      existing evidence for an impairment of externally guided motor preparation in
      schizophrenia is most likely due to a deficit in selective attention to the
      external input, which lends support to theories proposing that the primary
      cognitive deficit in schizophrenia concerns the processing of input information.

PMID- 19762087
TI  - Increased personal space of patients with schizophrenia in a virtual social
      environment.
AB  - Virtual reality may be a good alternative method for measuring personal space and
      overcoming some limitations in previous studies on the social aspects of
      schizophrenia. Using this technology, we aimed to investigate the characteristics
      of personal space in patients with schizophrenia and evaluate the relationship
      between their social behaviors and schizophrenic symptoms. The distance from a
      virtual person and the angle of head orientation while talking to a virtual
      person in a virtual environment were measured in 30 patients with schizophrenia
      and 30 normal controls. It was found that patients with schizophrenia had longer
      distances and larger angles than did normal controls. The severity of the
      negative syndrome had significant inverse correlations with the distance from the
      angry and neutral virtual persons and with the angle of head orientation toward
      the happy and angry virtual persons, suggesting that negative symptoms may have a
      close relationship with personal space, including distancing and eye gaze. The
      larger personal space of patients may reflect their discomfort in close
      situations or cognitive deficits. Showing these profiles to patients could help
      them realize the amount of personal space they need.

PMID- 19762088
TI  - L-epinephrine and dexamethasone in postextubation airway obstruction: a
      prospective, randomized, double-blind placebo-controlled study.
AB  - PURPOSE: This prospective randomized double-blind placebo-controlled study paired
      trial groups to investigate the effect of intravenous dexamethasone and nebulized
      L-epinephrine on the clinical development of postextubation laryngeal edema.
      MATERIAL AND METHODS: Sixty-four patients aged 1 day to 12 years who needed
      intubation from August/1997 to February/1999 in the Pediatric Intensive Care Unit
      (PICU) of Santa Casa de Sao Paulo School of Medicine were paired according to
      age, height and weight, anthropometric z-scores, duration of tracheal intubation
      and number of intubation attempts. Patients received intravenous dexamethasone
      (0.2mg/kg every 6h), with or without nebulized L-epinephrine (0.5mg/kg every 4h)
      in the study groups; in the control groups, they received nebulized or
      intravenous isotonic saline solution, or both. DEPENDENT VARIABLES: frequency and
      severity of the laryngeal edema (according to Westley Clinical Scoring System),
      as well as the time interval (min) between extubation and the first
      postextubation laryngeal edema scores. Postextubation respiratory rate and
      transcutaneous oxygen saturation were employed as indicators of the clinical
      conditions for extubation. RESULTS: Laryngeal edema frequencies did not change
      according to treatments, chi(2) (3, N=64)=0.58, p>0.05, and the highest scores
      were not reached in the 24h after extubation, chi(ranks)(2) (3, N=16)=1.03,
      p>0.05. CONCLUSIONS: Dexamethasone and l-epinephrine did not reduce the clinical
      progression of airway obstruction due to laryngeal edema in the early
      postextubation period.

PMID- 19762089
TI  - Sodium valproate: an old drug with new roles.
AB  - Sodium valproate, or Epilim, has been widely used as a broad spectrum,
      anticonvulsant drug for over 40 years and exhibits a good safety profile. Some of
      the actions of valproate arise from its more recently described histone
      deacetylase (HDAC) inhibitory properties and hence it can specifically modulate
      gene expression. There is now accumulating evidence that HDAC inhibitors may have
      potential in the treatment of CNS disorders and, in this context, valproate has
      much potential as a brain-penetrant, clinically available and well tested drug.
      This article reviews the pharmacology of this remarkable molecule, focusing on
      its actions as a neuroprotectant and hence with new potential in the treatment of
      neurodegenerative diseases.

PMID- 19762090
TI  - Cardiomyocytes from human pluripotent stem cells in regenerative medicine and
      drug discovery.
AB  - Stem cells derived from pre-implantation human embryos or from somatic cells by
      reprogramming are pluripotent and self-renew indefinitely in culture. Pluripotent
      stem cells are unique in being able to differentiate to any cell type of the
      human body. Differentiation towards the cardiac lineage has attracted significant
      attention, initially with a strong focus on regenerative medicine. Although an
      important research area, the heart has proven challenging to repair by
      cardiomyocyte replacement. However, the ability to reprogramme adult cells to
      pluripotent stem cells and genetically manipulate stem cells presented
      opportunities to develop models of human disease. The availability of human
      cardiomyocytes from stem cell sources is expected to accelerate the discovery of
      cardiac drugs and safety pharmacology by offering more clinically relevant human
      culture models than presently available. Here we review the state-of-the-art
      using stem cell-derived human cardiomyocytes in drug discovery, drug safety
      pharmacology, and regenerative medicine.

PMID- 19762091
TI  - Is resistance useless? Multidrug resistance and collateral sensitivity.
AB  - When cancer cells develop resistance to chemotherapeutics, it is frequently
      conferred by the ATP-dependent efflux pump P-glycoprotein (MDR1, P-gp, ABCB1). P
      gp can efflux a wide range of cancer drugs; its expression confers cross
      resistance, termed "multidrug resistance" (MDR), to a wide range of drugs.
      Strategies to overcome this resistance have been actively sought for more than 30
      years, yet clinical solutions do not exist. A less understood aspect of MDR is
      the hypersensitivity of resistant cancer cells to other drugs, a phenomenon known
      as "collateral sensitivity" (CS). This review highlights the extent of this
      effect for the first time, and discusses hypotheses (e.g. generation of reactive
      oxygen species) to account for the underlying generality of this phenomenon, and
      proposes exploitation of CS as a strategy to improve response to chemotherapy.

PMID- 19762092
TI  - Precaution, cyclooxygenase inhibition, and cardiovascular risk.
AB  - Cardiovascular risk led to the withdrawal of Vioxx (rofecoxib) in 2004. Some
      related drugs also increase cardiovascular risk and cyclooxygenase (COX)-2
      inhibitors that remain on the market, including unselective non-steroidal anti
      inflammatory drugs (NSAIDs), have not been exonerated. This article reviews if
      new evidence should change clinical and regulatory practice. Substantial COX-2
      inhibition increases the incidence of cardiovascular disease unless concomitant
      platelet thromboxane production is inhibited by >95%. This can be investigated
      using whole blood assays, an approach used recently to show that acetaminophen
      (paracetamol) is a COX-2-selective inhibitor. The epidemiology available suggests
      acetaminophen, though readily available over-the-counter, does increase
      cardiovascular risk. Current evidence is inadequate to recommend many potential
      alternatives to Vioxx as safe. We argue that the precautionary principle, 'first
      do no harm', should underpin the regulation and prescribing of NSAIDs. Labelling
      which identifies these risks for prescribers and consumers should be mandatory.

PMID- 19762093
TI  - Adenosine receptors as targets for therapeutic intervention in asthma and chronic
      obstructive pulmonary disease.
AB  - Asthma and chronic obstructive pulmonary disease (COPD) are pulmonary disorders
      characterized by various degrees of inflammation and tissue remodeling. Adenosine
      is a signaling molecule that is elevated in the lungs of patients with asthma and
      COPD. Adenosine elicits its actions by engaging cell surface adenosine receptors,
      and substantial preclinical evidence suggests that targeting these receptors will
      provide novel approaches for the treatment of asthma and COPD. Studies in animal
      models of airway disease suggest that there may be clinical benefit to the use of
      A(1), A(3) and A(2B) adenosine receptor antagonists in the treatment of features
      of asthma and/or COPD, while A(2A) agonists may also prove effective. Several
      adenosine receptor based pharmacologic agents have entered clinical development
      for the treatment of asthma and COPD; however, the studies have been limited and
      the efficacy of such approaches is not yet clear.

PMID- 19762095
TI  - Echocardiographic characteristics of the criss-cross heart.
AB  - OBJECTIVE: To assess the ultrasonic characteristics of the criss-cross heart, and
      explore the value of echocardiography in the diagnosis of this rare congenital
      cardiac defect. METHODS: We reviewed the echocardiographic findings in 4 patients
      having criss-crossed atrioventricular connections at our hospital, and compared
      the findings with observations at surgery in 3 of the patients. RESULTS: In all 4
      patients, there was usual atrial arrangement, right hand ventricular topology,
      and concordant atrioventricular connections. The inlet components of the
      ventricular mass, however, crossed such that the apical component of the
      morphologically right ventricle was situated anteriorly and superiorly, and
      extended to the left relative to the apex of the morphologically left ventricle.
      The ventriculo-arterial connections were concordant in 1 patient, double outlet
      from the morphologically right ventricle in 2, and discordant in the other. In
      all 4 patients, it proved impossible to obtain the standard 4-chamber view
      showing simultaneously all four chambers and both atrioventricular valves. A
      series of apical 4-chamber or subcostal coronal views, obtained by tilting the
      transducer from posterior to anterior, demonstrate initially the connection of
      the left-sided left atrium and the right-sided left ventricle through the mitral
      valve. More anterior angulation of the transducer then showed the right-sided
      right atrium to be connected to the left-sided right ventricle through the
      tricuspid valve, confirming the presence of twisted atrioventricular connections.
      Color Doppler imaging displayed the crossing of the atrioventricular connections
      without mixing of the streams. Short-axis views across the ventricular mass
      confirmed that the right ventricle was superior, anterior, and to the left of the
      left ventricle, and demonstrated the horizontal position of the ventricular
      septum. When viewed subcostally, the distance between the tricuspid valve and the
      orifice of the inferior vena cava was significantly increased relative to normal
      findings. The echocardiographic findings were confirmed during surgical
      interventions in 3 patients, apart from the failure to diagnose one instance of
      persistent patency of the left superior vena cava. CONCLUSIONS: The failure to
      obtain a characteristic 4-chamber view in any cut was diagnostic for recognition
      of the criss-crossed atrioventricular junctions. Transthoracic echocardiography
      provides definitive images of this rare arrangement, and accurately defines the
      associated cardiac abnormalities.

PMID- 19762094
TI  - The "toll" of opioid-induced glial activation: improving the clinical efficacy of
      opioids by targeting glia.
AB  - Glial activation participates in the mediation of pain including neuropathic
      pain, due to release of neuroexcitatory, proinflammatory products. Glial
      activation is now known to occur in response to opioids as well. Opioid-induced
      glial activation opposes opioid analgesia and enhances opioid tolerance,
      dependence, reward and respiratory depression. Such effects can occur, not via
      classical opioid receptors, but rather via non-stereoselective activation of toll
      like receptor 4 (TLR4), a recently recognized key glial receptor participating in
      neuropathic pain as well. This discovery identifies a means for separating the
      beneficial actions of opioids (opioid receptor mediated) from the unwanted side
      effects (TLR4/glial mediated) by pharmacologically targeting TLR4. Such a drug
      should be a stand-alone therapeutic for treating neuropathic pain as well.
      Excitingly, with newly-established clinical trials of two glial modulators for
      treating neuropathic pain and improving the utility of opioids, translation from
      rats-to-humans now begins with the promise of improved clinical pain control.

PMID- 19762096
TI  - Trends on acute Chagas' disease transmitted by oral route in Brazil: steady
      increase in new cases and a concealed residual fluctuation.

PMID- 19762097
TI  - LQTS mutation N1325S in cardiac sodium channel gene SCN5A causes cardiomyocyte
      apoptosis, cardiac fibrosis and contractile dysfunction in mice.
AB  - OBJECTIVE: Mutations in the cardiac sodium channel gene SCN5A cause long QT
      syndrome (LQTS). We previously generated an LQTS mouse model (TG-NS) that
      overexpresses the LQTS mutation N1325S in SCN5A. The TG-NS mice manifested the
      clinical features of LQTS including spontaneous VT, syncope and sudden death.
      However, the long-term prognosis of LQTS on the structure of the heart has not
      been investigated in this or any other LQTS models and human patients. METHODS
      AND RESULTS: Impaired systolic function and reduced left ventricular fractional
      shortening were detected by echocardiography, morphological and histological
      examination in two lines of adult mutant transgenic mice. Histological and TUNEL
      analyses of heart sections revealed fibrosis lesions and increased apoptosis in
      an age-dependent manner. Cardiomyocyte apoptosis was associated with the
      increased activation of caspases 3 and 9 in TG-NS hearts. Western blot analysis
      showed a significantly increased expression of the key Ca(2+) handling proteins L
      type Ca(2+) channel, RYR2 and NCX in TG-NS hearts. Increased apoptosis and an
      altered expression of Ca(2+) handling proteins could be detected as early as
      3months of age when echocardiography showed little or no alterations in TG-NS
      mice. CONCLUSIONS: Our findings revealed for the first time that the LQTS
      mutation N1325S in SCN5A causes cardiac fibrosis and contractile dysfunction in
      mice, possibly through cellular mechanisms involving aberrant cardiomyocyte
      apoptosis. Therefore, we provide the experimental evidence supporting the notion
      that some LQTS patients have an increased risk of structural and functional
      cardiac damage in a prolonged disease course.

PMID- 19762098
TI  - Evaluation of Ziehl-Neelsen stained faecal smear and ELISA as tools for
      surveillance of clinical paratuberculosis in cattle in the Netherlands.
AB  - Testing cattle suspected of clinical paratuberculosis is an important element of
      surveillance of paratuberculosis. The aim of this study was to evaluate the
      diagnostic-test characteristics of microscopic examination of Ziehl-Neelsen
      stained faecal smears for acid-fast Mycobacteria (ZN-test) and serum-ELISA in
      cattle suspected of clinical paratuberculosis in the Netherlands. Results of all
      samples submitted for ZN-test and serum-ELISA between April 2003 and April 2006
      to our laboratory were retrieved. Results from cattle for which both tests were
      performed were analysed using two Bayesian latent-class models for evaluation of
      diagnostic tests in two populations without a gold standard, assuming (a)
      conditional independence of tests, or (b) conditional dependence of tests in both
      infected and non-infected cattle. Sampled cattle were divided into two
      populations in different ways using four known risk factors for clinical
      paratuberculosis: region, soil type, clinical signs, and age. For 892 cattle
      suspected of clinical paratuberculosis, both ZN-test and serum-ELISA results were
      retrieved: 250 ZN-positive and ELISA-positive, 12 ZN-positive and ELISA-negative,
      260 ZN-negative and ELISA-positive, and 370 ZN-negative and ELISA-negative
      cattle. With priors based on the available literature, the posterior estimates of
      sensitivity, specificity, and positive and negative predictive values of the
      ELISA were always higher than those of the ZN-test. Furthermore, lower limits of
      the 95% credibility intervals of the posterior positive predictive values of the
      ELISA were >or=99.7%, and of the negative predictive values of the ELISA
      >or=56.4%. We conclude that the ELISA is preferred to the ZN-test to confirm the
      presumptive diagnosis of clinical paratuberculosis in the Netherlands. Little
      diagnostic information can be gained by performing the ZN-test in addition to the
      ELISA.

PMID- 19762099
TI  - Herd size and bovine tuberculosis persistence in cattle farms in Great Britain.
AB  - Bovine tuberculosis (bTB) infection in cattle is one of the most complex and
      persistent problems faced by the cattle industry in Great Britain today. While a
      number of factors have been identified as increasing the risk of infection, there
      has been little analysis on the causes of persistent infection within farms. In
      this article, we use the Cattle Tracing System to examine changes in herd size
      and VetNet data to correlate herd size with clearance of bTB. We find that the
      number of active farms fell by 16.3% between 2002 and 2007. The average farm size
      increased by 17.9% between 2002 and 2005. Using a measure similar to the Critical
      Community Size, the VetNet data reveal that herd size is positively correlated
      with disease persistence. Since economic policy and subsidies have been shown to
      influence farm size, we used a simple financial model for ideal farm size which
      includes disease burden to conclude that increasing herd size for efficiency
      gains may contribute to increased disease incidence.

PMID- 19762100
TI  - Risk-based sample size calculation for consecutive surveys to document freedom
      from animal diseases.
AB  - International trade regulations require disease freedom to be documented. This is
      generally achieved by national random surveys. Risk-based sample size
      calculations can reduce both the sample size and the costs for repeated surveys
      by one-third compared to traditional sample size calculations based on random
      sampling. In this approach, information from previous surveys can reduce the
      sample size of a new survey while maintaining its overall level of confidence.
      Risk-based sample size calculations have only formerly been described for one
      single survey and not when applied consecutively. Based on the existing
      deterministic origin of risk-based methods and sample size calculations, we
      devised a further development of sample size calculation to document freedom from
      non-highly contagious diseases. We show that for a repeated risk-based sample
      size calculation not only does the loss of confidence due to the risk of disease
      import and the risk of undetected disease within the country need to be
      calculated between the two surveys, but the time value of historical testing
      information also needs to be considered. As the order of surveys is important, a
      separate process, capable of calculating the time value of information from all
      conducted surveys, needs to be incorporated in the sample size calculation. This
      paper suggests how to use information from previous surveys in a risk-based
      approach for sample size calculations in consecutive surveys considering the
      adjusted time value of historical testing information, import risk assessments
      and the risk of disease spread within the country. Thus, the reduction of
      confidence between two surveys is adequately estimated. The results of sample
      size calculations for surveys over various years, under different conditions,
      show that the risk-based approach, including import risk assessments and adjusted
      time value of historical testing information, could reduce the sample size of
      annual surveys by 25% compared to the sample sizes calculated without a risk
      based technique. The presented risk-based sample size calculation is appropriate
      for the requirements of consecutive surveys and outlines how the adjusted time
      value of historical testing information should be considered in this context.
      When planning to undertake repeated surveys to document freedom from disease,
      this method can easily be used to calculate sample sizes and consequently reduce
      them.

PMID- 19762101
TI  - The impact of oxygen availability on stress survival and radical formation of
      Bacillus cereus.
AB  - Both the growth and stress survival of two model Bacillus cereus strains, ATCC
      14579 and ATCC 10987, were tested in three different conditions varying in oxygen
      availability, i.e., aerobic, microaerobic and anaerobic conditions. Both B.
      cereus strains displayed highest growth rates and yields under aerobic
      conditions, whereas the microaerobic and anaerobic cultures showed similar
      reduced growth performances. The cells grown and exposed microaerobically and
      anaerobically were more resistant to heat and acid than cells that were cultured
      and exposed aerobically. On the other hand, the anaerobically grown cells were
      more sensitive to hydrogen peroxide compared to the (micro)aerobically grown
      cells. The increased heat- and acid-induced inactivation in aerobic conditions
      appeared to be associated with intracellular accumulation of excess hydroxyl
      and/or peroxynitrite radicals, as determined by flow cytometry in combination
      with the fluorescent reporter dye 3'-(p-hydroxyphenyl) fluorescein. This suggests
      that radical formation may contribute to inactivation of bacteria in the presence
      of oxygen, such as in aerobic and microaerobic conditions. No evidence was found
      for radical formation upon exposure to salt and hydrogen peroxide. The increased
      resistance to heat and acid in microaerobic and anaerobic conditions shows that
      oxygen availability should be taken into account when behavior of bacteria, such
      as B. cereus, in food industry related conditions is investigated, because oxygen
      availability may affect the efficiency of food preservation conditions.

PMID- 19762102
TI  - Probabilistic model for contamination of egg dishes with Salmonella spp. made
      from shell eggs produced on the island of Ireland.
AB  - A quantitative model was constructed to estimate the probability that a serving
      of food containing eggs produced on the island of Ireland is contaminated with
      Salmonella spp. The model is based on the prevalence of contaminated eggs at the
      time of lay and a set of parameters which describe the pooling of eggs in the
      home and in catering situations. Both external and internal contamination of the
      eggs by Salmonella spp. was considered. The model estimates that there is a 90%
      chance that the probability of a serving of food being contaminated is between
      0.0043% and 0.038%. Sensitivity analysis demonstrated that egg prevalence drives
      this low probability and that, at the current level of egg prevalence at the time
      of lay, pooling of eggs has a minor effect. These results indicate the importance
      of maintaining the low prevalence of contaminated eggs at the time of lay to
      minimise the risk of human cases of salmonellosis from consumption of eggs.

PMID- 19762103
TI  - Preparation of fungal conidia impacts their susceptibility to inactivation by
      ethanol vapours.
AB  - A common protocol employed for the preparation of conidia employs flooding a
      fungal colony grown on semi-solid media under optimum conditions with an aqueous
      solution. In contrast, conidia produced in a natural environment are usually not
      hydrated when disseminated in air and can be produced under water stress. In
      order to simulate the latter conditions, cultures were grown at different water
      activities and conidia were dry-harvested on the lid by turning the dishes upside
      down then gently tapping the bottom of the box. This study aimed at assessing the
      effect of the preparation of fungal conidia on their inactivation by ethanol
      vapours. Firstly ethanol vapours (either 0.30 or 0.45 kPa) were applied to
      conidia obtained from the standardised protocol and to dry-harvested conidia for
      some species of Penicillium. While all dry-harvested conidia remained viable
      after 24 h of treatment, about 1.0, 3.5 and 2.5 log(10) reductions were observed
      for hydrated conidia of Penicillium chrysogenum, Penicillium digitatum and
      Penicillium italicum respectively. Secondly ethanol vapours (0.67 kPa) were
      applied to dry-harvested conidia obtained from cultures grown at 0.99 a(w) and at
      reduced water activities. For all species, the susceptibility to ethanol vapours
      of conidia obtained at 0.99 a(w) was significantly greater than that of conidia
      obtained at reduced water activities. Conidia produced in a natural environment
      under non-optimal conditions would be much more resistant to ethanol vapours than
      those produced in the laboratory. This phenomenon may be due to a reduced
      intracellular water activity of dry-harvested conidia.

PMID- 19762104
TI  - Hepatitis C after simultaneous liver-kidney transplantation.

PMID- 19762105
TI  - Study on doctor shopping behavior: insight from patients with upper respiratory
      tract infection in Taiwan.
AB  - OBJECTIVES: Based on the actual medical records of ambulatory care visits, this
      study analyzed patients' healthcare seeking behavior and doctor shopping behavior
      (DSB), and investigated the underlying factors and the impact on the depletion of
      the healthcare resources for health policy makers to build a better health
      delivery system. METHODS: Among a cohort comprised of 200,000 patients randomly
      chosen from the National Health Insurance Research Database of Taiwan in 2004,
      only the patients seeking ambulatory care visits for upper respiratory tract
      infection (URI) were analyzed. RESULTS: Among the 45,951 URI patients, 2875 of
      them exhibited DSB (prevalence 6.3%). The DSB showed a reverse U-shaped
      relationship with the patient age (the highest DSB in age 18-34 years). The
      episodes of the URI had a negative impact on the DSB. The odds ratios of gender
      and the frequency of consultation versus DSB were 1.10 and 4.72, respectively,
      and the depletion of days of medication and repeat prescription increased with
      doctor shopping. CONCLUSIONS: Health education to raise DSB awareness is
      necessary, especially for female's age 18-34 years. Implementing a proper
      referral system with efficient data exchange, setting up control parameters in
      the IC cards, and strengthening the integrated care plan could reduce the
      unnecessary waste of the healthcare resources.

PMID- 19762106
TI  - Evaluating community pharmacists' perceptions of future generic substitution
      policy implementation: a national survey from Malaysia.
AB  - OBJECTIVES: This study aims to provide baseline data to support the
      implementation of generic substitution policy in Malaysia by evaluating the
      community pharmacists' perceptions and opinions on generic substitution and
      current substitution practices. METHODS: A cross-sectional descriptive study
      involving the entire population of Malaysian community pharmacies (n=1419) was
      undertaken using a self-completed anonymous mail questionnaire. RESULTS: A total
      of 219 responses were received for a response rate of 15.4%. Majority of the
      respondents (93.6%) agreed that pharmacists should have generic substitution
      rights. Almost all pharmacists (96.8%) viewed Poison Class C (pharmacist only
      medicine) as most suitable class of controlled medicines for substitution. About
      half (51.6%) of the pharmacists preferred a policy which allowed substitution on
      any prescription. The pharmacists prefer to consult the physician when
      substituting narrow therapeutic index medicines (88.1%) and prescription only
      medicines (51.3%). Less than 25.0% of the pharmacists routinely keep the
      medication records and follow-up the patients who received substitution.
      Monitoring the efficacy (79.2%) and patient's satisfaction with the generic
      medicines (74.9%) were the main reasons for following-up the patient if
      substitution occurs. CONCLUSIONS: Malaysian community pharmacists are generally
      in favour of generic substitution policy implementation.

PMID- 19762107
TI  - Prediction of externally applied forces to human hands using frequency content of
      surface EMG signals.
AB  - In this work, a new signal processing method was proposed in order to predict
      externally applied forces to human hands by deriving a relationship between the
      surface electromyographic (SEMG) signals and experimentally known forces. This
      relationship was investigated by analyzing the spectral features of the SEMG
      signals. SEMG signals were recorded from three subjects during isometric
      contraction and from another three subjects during anisometric contraction. In
      order to determine force-SEMG signal relationship, higher order frequency moments
      (HOFMs) of the signals were calculated and used as characterizing features of
      SEMG signals. Subsequently, artificial neural networks (ANN) with backpropagation
      algorithm were trained by using the HOFMs. Root mean square difference (RMSD)
      between the actual and predicted forces was calculated to evaluate force
      prediction performance of the ANN. In addition to RMSD, cross-correlation
      coefficients between actual and predicted force time histories were also
      calculated for anisometric experiment results. The RMSD values ranged from 0.34
      and 0.02 in the isometric contraction experiments. In the anisometric contraction
      tests, RMSD results were between 0.23 and 0.09 and cross-correlation coefficients
      ranged from 0.91 to 0.98. In order to compare the performance of the HOFMs with a
      widely used EMG signal processing technique, root-mean-squared (RMS) values of
      the EMG signals were also calculated and used to train the ANN as another
      characterizing feature of the signal. Predicted forces using HOFMs technique were
      in general closer to the actual forces than those of obtained by using RMS
      values. The results indicated that the proposed signal processing method showed
      an encouraging performance for predicting the forces applied to the human hands,
      and the spectral features of the EMG signal might be used as input parameter for
      the myoelectric controlled prostheses.

PMID- 19762108
TI  - THE-MUSS: Mobile u-health service system.
AB  - In this paper, we introduce a mobile u-health service system called THE-MUSS. THE
      MUSS supports the development and running of u-health services with functions,
      modules, and facilities that are commonly required for various mobile u-health
      services. Aiming to achieve reusability and evolvability design goals, basic
      modules to support bio-signal capturing, processing, analysis, diagnosis, and
      feedback are developed and stacked in the layered architecture of THE-MUSS. A U
      health service platform, design tool, portal, and matrix-based disease group
      identification method are the major components constituting the THE-MUSS
      architecture. We confirmed that THE-MUSS is practically useful for mobile u
      health services by developing mobile stress and weight management services on THE
      MUSS. The more u-health services are developed in THE-MUSS, the better services
      it can provide in the future.

PMID- 19762109
TI  - Age, tumor size, type of surgery, and gender predict survival in early stage
      (stage I and II) non-small cell lung cancer after surgical resection.
AB  - BACKGROUND: Even after presumably curative resection the 5-year survival rates
      are only 60-80% in stage I and 40-50% in stage II NSCLC. Purpose of the present
      study was the identification of independent clinico-pathological predictors of
      their survival. METHODS: A retrospective review of 519 consecutive subjects who
      had undergone attempted curative resection for stage I or II NSCLC was performed.
      Patients who had received any adjuvant or neo-adjuvant chemo- or radiation
      therapy were excluded. Primary outcome measure was the duration of overall
      survival. RESULTS: Median survival was 7.25 years for stage IA, 5.71 years for
      stage IB and 3.85 years for stage IIB. In univariate analysis, six variables were
      significantly associated (p-value<0.05) with poorer survival: older age, larger
      size of the tumor, male gender, surgery other than lobectomy, squamous histology
      and later stages (stage IB and IIB). In multivariate analysis, age (Hazard
      ratio=1.06 per year increase in age; p<0.0001), larger tumor size (Hazard
      ratio=1.54 per doubling of tumor size; p<0.0001), type of surgery (Hazard
      ratio=1.50 for surgery other than lobectomy; p=0.036), and gender (Hazard
      ratio=1.45 for male gender; p=0.039) were the predictors of overall survival.
      CONCLUSIONS: In surgically treated early stage (I and II) NSCLC patients, age,
      tumor size, type of surgery, and gender are the important predictors of survival.

PMID- 19762110
TI  - Using erlotinib to treat patients with non-small cell lung cancer who continue to
      smoke.
AB  - Erlotinib is active for unselected patients with advanced non-small cell lung
      cancer. Patients who smoke, however, are less likely to respond and less likely
      to experience toxicity. These patients rapidly metabolize erlotinib and
      experience lower drug exposure when treated with standard doses. A recent dose
      escalation study established 300 mg daily as the recommended Phase II dose in
      patients who continue to smoke. Pharmacokinetic profiles of erlotinib in current
      smokers taking 300 mg daily were comparable to non-smokers taking 150 mg daily.
      Current smokers taking 300 mg daily had a toxicity profile comparable to the
      toxicity profile for patients in the BR.21 trial. Determining the best strategy
      for overcoming erlotinib resistance may require understanding both
      pharmacokinetic and tumor-specific resistance mechanisms. Individually, the
      selection and dosing of erlotinib for the treatment of lung cancer patients who
      continue to smoke is a clinical challenge.

PMID- 19762111
TI  - Social and coevolutionary feedbacks between mating and parental investment.
AB  - A survey of empirical studies relating mating and parental investment reveals as
      many unpredicted patterns as results supporting existing hypotheses. This leaves
      us with individual post hoc explanations of observed patterns rather than an
      ability to make strong a priori predictions. I argue here that our ability to
      explain and predict empirical patterns can be improved by considering how social
      interactions and coevolutionary dynamics affect male and female reproductive
      traits. Recent research suggests that these social and coevolutionary feedbacks
      can increase our understanding of empirical patterns, while suggesting new
      directions of research. I also describe a social and coevolutionary dynamics
      modelling approach that integrates ideas from reproductive cooperation and sexual
      conflict to increase understanding of mating and parental investment.

PMID- 19762112
TI  - The costs of chronic noise exposure for terrestrial organisms.
AB  - Growth in transportation networks, resource extraction, motorized recreation and
      urban development is responsible for chronic noise exposure in most terrestrial
      areas, including remote wilderness sites. Increased noise levels reduce the
      distance and area over which acoustic signals can be perceived by animals. Here,
      we review a broad range of findings that indicate the potential severity of this
      threat to diverse taxa, and recent studies that document substantial changes in
      foraging and anti-predator behavior, reproductive success, density and community
      structure in response to noise. Effective management of protected areas must
      include noise assessment, and research is needed to further quantify the
      ecological consequences of chronic noise exposure in terrestrial environments.

PMID- 19762113
TI  - A reality check for designer biofuel landscapes.

PMID- 19762116
TI  - Invasive species can also be native...

PMID- 19762118
TI  - Invasive pulmonary aspergillosis in intensive care units: is it a real problem?

PMID- 19762119
TI  - Biocide-tolerant multidrug-resistant Acinetobacter baumannii clinical strains are
      associated with higher biofilm formation.

PMID- 19762120
TI  - Inpatient treatment patterns, outcomes, and costs of skin and skin structure
      infections because of Staphylococcus aureus.
AB  - BACKGROUND: Staphylococcus aureus (SA) is a common bacterial pathogen in skin and
      skin structure infections (SSSIs). Limited data exist on hospital treatment
      patterns and costs for SA-SSSIs. METHODS: This retrospective analysis examined
      the lengths of stay, treatment patterns, and costs of hospitalized patients with
      an SA-SSSI diagnosis using a nationally representative inpatient database.
      Patients were selected if they had an ICD-9-CM diagnosis of an SSSI with SA noted
      between January 2005 and June 2006, received a study antibiotic (ie, intravenous
      [IV] vancomycin, IV or oral linezolid, and IV daptomycin), and were not in the
      intensive care unit before receiving a study antibiotic. Generalized linear
      models assessed predictors of length of stay and costs. Costs are expressed in
      2005 US dollars. RESULTS: Thirteen thousand four hundred thirty-three patients
      met the selection criteria and mean (+/-SD) age was 48.2 (+/-18.3) years. Forty
      percent of patients received a nonstudy antibiotic before receiving their first
      study antibiotic. Ninety-five percent were prescribed vancomycin as their first
      study antibiotic. Study antibiotics were administered for an average of 4.3 days,
      and 8% of patients switched study antibiotics. Nineteen percent of patients
      receiving IV linezolid stepped down to oral linezolid. Mean (+/-SD) lengths of
      hospital stay and costs were 6.1 (+/-6.0) days and $6830 (+/-$7100). In-hospital
      mortality, switching antibiotics, and diagnoses of selected complications or
      comorbidities were associated with increased lengths of stay and costs. Younger
      age, location outside the Northeast, and use of oral linezolid were associated
      with lower lengths of stay and costs. CONCLUSION: The costs of treating inpatient
      SA-SSSIs are substantial and vary by patient demographics and treatment
      characteristics.

PMID- 19762121
TI  - [Prescription pressure in primary care].

PMID- 19762122
TI  - [Error in the interpretation of an abuse questionnaire].

PMID- 19762123
TI  - [The meaning of the word "over use" for primary care professionals].

PMID- 19762124
TI  - [Hidden cocaine consumption in neurological emergencies].

PMID- 19762125
TI  - Dialkylamino and nitrogen heterocyclic analogues of hexadecylphosphocholine and
      cetyltrimetylammonium bromide: effect of phosphate group and environment of the
      ammonium cation on their biological activity.
AB  - A series of dialkylamino and nitrogen heterocyclic analogues of
      hexadecylphosphocholine and cetyltrimethylammonium bromide have been synthesized.
      The prepared compounds exhibit significant cytotoxic, antifungal and
      antiprotozoal activities. Alkylphosphocholines possess higher antifungal activity
      against Candida albicans in comparison with quaternary ammonium compounds.
      However, quaternary ammonium compounds exhibit significant higher activity
      against human tumor cells and Acanthamoeba lugdunensis compared to
      alkylphosphocholines. In addition, their haemolytic toxicity has been
      investigated. The relationship between structure and biological activity of the
      tested compounds is discussed.

PMID- 19762126
TI  - Synthesis and pharmacological evaluation of sulfamide-based analogues of
      anandamide.
AB  - Arachidonyl and linoleyl sulfamide derivatives have been synthesized and their
      potential cannabimimetic properties evaluated in in vitro functional and binding
      assays. Replacement of the ethanolamide moiety of anandamide by -CH(2)NHSO(2)NH-R
      considerably reduces the CB1 receptor activity and only some of the compounds
      showed modest cannabinoid properties in binding assays. The new compounds were
      also tested as inhibitors of the FAAH enzyme but were inactive.

PMID- 19762127
TI  - [Limb arteritis in Horton disease: five cases].
AB  - INTRODUCTION: Giant cell arteritis of the limbs is rarely reported. It may be
      underestimated because it is usually asymptomatic. The aim of this study was to
      describe the distinctive features of this involvement. METHODS: Retrospective
      study of 50 patients with giant cell arteritis diagnosed from January 1985 to
      December 2007, satisfying the American college of rheumatology (ACR)
      classification criteria. All five patients had typical lesion at examination of
      temporal artery biopsy. Among these patients, those with ischemic manifestations
      of the limbs were selected. All patients disclosed elevated acute phase reactants
      and typical radiological findings. Temporal artery histopathology was made
      necessary to select patients. RESULTS: Five female (mean age: 66.8 years) out of
      50 patients (10%) with temporal arteritis presented with symptomatic limb
      arteriopathy. Limb arteritis was the presenting feature in four patients.
      Clinical presentation was similar to other non-inflammatory arteritis. One
      patient presented with involvement of her four limbs. Typical arteriographic
      abnormalities were presents in all patients (occlusion or moniliform stenosis
      without atheromatous lesions). Despite therapy with corticosteroids associated to
      anticoagulants or antiplatelet drugs, four amputations were necessary.
      CONCLUSION: Specific limb involvement may be the presenting feature of temporal
      arteritis. It can mimic arteriosclerosis vascular disease, particularly prevalent
      in this age group.

PMID- 19762128
TI  - Fractionation of natural radionuclides in soils from the vicinity of a former
      uranium mine Zirovski vrh, Slovenia.
AB  - As a result of former uranium mining and milling activities at Zirovski vrh,
      Slovenia, 0.6 million tons of uranium mill tailings (UMT) were deposited onto a
      nearby waste pile Borst. Resulting enhanced levels of natural radionuclides in
      UMT could pose threat for the surrounding environment. Therefore, sequential
      extraction protocol was performed to assess mobility and bioavailability of
      (238)U, (234)U, (230)Th and (226)Ra in soils from the waste pile and its
      surrounding. The radionuclides associated with exchangeable, organic, carbonate,
      Fe/Mn oxides and residual fraction, respectively, were determined. Results showed
      that the highest activity concentrations for the studied radionuclides were on
      the bottom of the waste pile. In non-contaminated locations, about 80% of all
      radionuclides were in the residual fraction. Considering activity concentrations
      in the UMT, (238)U and (234)U are the most mobile. Mobility of (226)Ra is
      suppressed by high sulphate concentrations and is similar to mobility of (230)Th.

PMID- 19762129
TI  - Defect in the nasal septum and maxillopalatine bone with an oronasal fistula:
      traumatic stimulation caused by a peculiar habit?
AB  - We report the case of a 25-year-old man with defects in the nasal septum and
      maxillopalatine bone and an oronasal fistula.

PMID- 19762130
TI  - Closure of the anterior open bite using mandibular sagittal split osteotomy.
AB  - Anterior open bite is a common problem in orthognathic practice that confers
      functional and aesthetic handicaps on affected patients. Its management varies,
      and it is one of the most challenging disorders to treat. The orthodontic and
      surgical approach to the treatment of skeletal anterior open bite is still
      debated, and the results are controversial. The relapse rate is high with all the
      techniques in current use. The cause of relapse is multifactorial and one of the
      main factors is the type of osteotomy used. Over the last 30 years preference has
      moved from mandibular sagittal split osteotomy (MSSO) alone, to maxillary
      procedures only, or to bimaxillary operations, with maxillary procedures alone
      being thought to confer the best stability and predictability. The aim of this
      study was to evaluate the results of correction of anterior open bite with the
      MSSO immediately after operation, and 1 year postoperatively.

PMID- 19762131
TI  - Patency of the radial artery following intra-luminal cannulation and its
      influence on potential flap harvest for head and neck reconstruction.
AB  - The radial forearm free flap (RFFF) is well-established in head and neck
      reconstruction, but early potential failure may necessitate a contingency plan,
      which could include the opposite RFFF if cannulation of the relevant artery at
      the time of the first operation did not influence its patency. We prospectively
      studied patients listed for major operations who required radial artery
      cannulation. They all had perioperative imaging of the radial artery with colour
      flow duplex before cannulation and at intervals after the cannula had been
      removed (2h-7 days). Forty patients were recruited (mean age 65 years, range 32
      91). Thirty-three had patent vessels within 2h of the cannula being removed, and
      39/40 at 24h. Patency after removal of the cannula returns rapidly, and is almost
      always complete by 24h. In most people the contralateral radial forearm could
      therefore be used to mode of salvage reconstruction if the flap failed early.

PMID- 19762132
TI  - Preoperative Doppler assessment of perforator anatomy in the anterolateral thigh
      flap.
AB  - Despite its many evident merits as a donor site, the principal disadvantage of
      the anterolateral thigh flap is the variability in its vascular anatomy.
      Preoperative assessment by Doppler of the vascular perforators has been advocated
      as routine. We report the accuracy of this method, and describe the strategy for
      rescue where adequate perforators are not evident. Eighty-six consecutive
      patients were marked preoperatively using hand-held Doppler and the pattern was
      compared with intraoperative findings. Assessment by Doppler predicted a median
      of 3 (range 0-8) perforator signals, and a median of 2 (range 0-5) was found
      intraoperatively. This overall trend towards false positives was exaggerated in
      thin thighs, but in the obese there were more false negative results. In 79% of
      cases explored medially it would have been possible to raise an apparently viable
      anteromedial thigh flap. As this can be done without extending the incision, it
      is the option of choice for rescue, although use of more proximal perforators may
      often be possible.

PMID- 19762133
TI  - The anterolateral thigh flap in head and neck reconstruction: "pearls and
      pitfalls".
AB  - The anterolateral thigh (ALT) flap has found a permanent and highly valued place
      in head and neck reconstruction because of its versatility, two-team method of
      operating, and favourable donor site. The principal disadvantages are related to
      unpredictable vascular anatomy and the need to meticulously dissect the
      perforator. With these issues in mind we present a series of practical "pearls
      and pitfalls". Our experience has not only given us more confidence to use this
      flap in an increasing variety of defects, but also given us a new perspective on
      the applicability of chimeric flaps and perforator techniques in a wide range of
      donor sites.

PMID- 19762134
TI  - Copper mobilization affected by weather conditions in a stormwater detention
      system receiving runoff waters from vineyard soils (Champagne, France).
AB  - Copper, a priority substance on the EU-Water Framework Directive list, is widely
      used to protect grapevines against fungus diseases. Many vineyards being located
      on steep slopes, large amounts of Cu could be discharged in downstream systems by
      runoff water. The efficiency of stormwater detention basins to retain copper in a
      vineyard catchment was estimated. Suspended solids, dissolved (Cu(diss)) and
      total Cu (Cu(tot)) concentrations were monitored in runoff water, upstream, into
      and downstream from a detention pond. Mean Cu(tot) concentrations in entering
      water was 53.6 microg/L whereas it never exceeded 2.4 microg/L in seepage.
      Cu(tot) concentrations in basin water (>100 microg/L in 24% of the samples)
      exceeded LC(50) values for several aquatic animals. Copper was principally
      sequestered by reduced compounds in the basin sediments (2/3 of Cu(tot)). Metal
      sequestration was reversible since sediment resuspension resulted in Cu
      remobilization. Wind velocity controlled resuspension, explained 70% of Cu(diss)
      variability and could help predicting Cu mobilization.

PMID- 19762135
TI  - Estimates of synthetic fertilizer N-induced direct nitrous oxide emission from
      Chinese croplands during 1980-2000.
AB  - There is increasing concern that agricultural intensification in China has
      greatly increased N(2)O emissions due to rapidly increased fertilizer use. By
      linking a spatial database of precipitation, synthetic fertilizer N input,
      cropping rotation and area via GIS, a precipitation-rectified emission factor of
      N(2)O for upland croplands and water regime-specific emission factors for
      irrigated rice paddies were adopted to estimate annual synthetic fertilizer N
      induced direct N(2)O emissions (FIE-N(2)O) from Chinese croplands during 1980
      2000. Annual FIE-N(2)O was estimated to be 115.7 Gg N(2)O-N year(-1) in the 1980s
      and 210.5 Gg N(2)O-N year(-1) in the 1990s, with an annual increasing rate of
      9.14 Gg N(2)O-N year(-1) over the period 1980-2000. Upland croplands contributed
      most to the national total of FIE-N(2)O, accounting for 79% in 1980 and 92% in
      2000. Approximately 65% of the FIE-N(2)O emitted in eastern and southern central
      China.

PMID- 19762136
TI  - Effects of amendments on the uptake and distribution of DDT in Cucurbita pepo ssp
      pepo plants.
AB  - The effects of soil amendments on the phytoextraction of summation operatorDDT
      (DDT + DDD + DDE) from soil ([ summation operatorDDT] approximately 1500 ng/g) by
      a pumpkin variety of Cucurbita pepo ssp pepo were tested and the patterns of
      summation operatorDDT storage throughout the plant shoot were examined. The soil
      amendments did not increase the total amount of summation operatorDDT extracted
      into plant shoots, but new information about summation operatorDDT distribution
      in the plants was obtained. As observed previously, the summation operatorDDT
      concentration in plant leaves (mean 290 ng/g) was significantly lower than in
      plant stems (mean 2600 ng/g). Further analysis revealed that summation
      operatorDDT composition was consistent throughout the plant shoot and that
      summation operatorDDT concentration in leaves and stems decreased exponentially
      as distance from the root increased, which was previously unknown. This new
      information about the patterns of summation operatorDDT uptake and translocation
      within pumpkin plants highlights the need for appropriate plant sampling
      strategies in future POPs phytoextraction research.

PMID- 19762137
TI  - Involuntary autonomy: patients' perceptions of physicians, conventional medicines
      and risks in the management of atopic dermatitis.
AB  - Consumerism is a major force in western health care. It defines the process in
      which patients should or do play a more active and central role in making
      informed choices about health and illness. The talk of patients as consumers is
      closely linked, and is especially pertinent for patients managing a chronic
      illness. This article presents findings from a Danish qualitative study that set
      out to broaden the sociological debate on patients as consumers by including
      patients' perceptions of conventional medicines. In-depth interviews were carried
      out with 24 people who medically managed their own or their child's atopic
      dermatitis. The informants were recruited via the Division of Dermatology in a
      Danish Hospital which was planning an Information Day on atopic dermatitis (AD).
      The findings reveal how many of the informants who on the surface appear to match
      the profile of the so called 'consumer', by being active, critical, informed
      etc., in fact prefer to consult a patient-centred medical expert (a
      dermatologist) with good communication skills, who is able to inform, advise and
      support on issues of managing atopic dermatitis. These people are not seeking
      more independence but rather a partnership where responsibility for treatment
      (medicines) is shared. This preference appears to be closely linked with a sense
      of insecurity about what an outbreak of atopic dermatitis may lead to and
      insecurity about the medicines. Ultimately, the findings stress that health care
      politicians and professionals need to reflect upon patient's wants and needs when
      designing future health care. Turning health care into self-care may not be an
      appropriate strategy.

PMID- 19762138
TI  - Age, cohort and period effects in the prevalence of sleep disturbances among
      older people: the impact of economic downturn.
AB  - Using two longitudinal and nationally representative datasets, this study employs
      a cross-cohort analysis to examine age, cohort and period effects in the
      prevalence of sleep loss through worry for people over the age of 50 in the UK.
      The likelihood of reporting sleep loss through worry is calculated at two time
      points for 7785 respondents from the Health and Activity Survey (HALs) and 21,834
      respondents from the English Longitudinal Study of Ageing (ELSA), with baseline
      information on sleep loss through worry. Descriptive statistical methods were
      applied to determine the prevalence rates in sleep loss through worry at each
      survey within both datasets. The results of analysis reveal that sleep loss
      through worry declined with age, but this pattern was tempered by a temporary
      increase in the early 1990s. The contemporary economic downturn is suggested as a
      possible explanation for the significant increase in the prevalence of sleep loss
      through worry in 1991.

PMID- 19762140
TI  - Congenital amusia: a short-term memory deficit for non-verbal, but not verbal
      sounds.
AB  - Congenital amusia refers to a lifelong disorder of music processing and is linked
      to pitch-processing deficits. The present study investigated congenital amusics'
      short-term memory for tones, musical timbres and words. Sequences of five events
      (tones, timbres or words) were presented in pairs and participants had to
      indicate whether the sequences were the same or different. The performance of
      congenital amusics confirmed a memory deficit for tone sequences, but showed
      normal performance for word sequences. For timbre sequences, amusics' memory
      performance was impaired in comparison to matched controls. Overall timbre
      performance was found to be correlated with melodic contour processing (as
      assessed by the Montreal Battery of Evaluation of Amusia). The present findings
      show that amusics' deficits extend to non-verbal sound material other than pitch,
      in this case timbre, while not affecting memory for verbal material. This is in
      line with previous suggestions about the domain-specificity of congenital amusia.

PMID- 19762139
TI  - Motivational systems in adolescence: possible implications for age differences in
      substance abuse and other risk-taking behaviors.
AB  - Adolescence is an evolutionarily conserved developmental phase characterized by
      hormonal, physiological, neural and behavioral alterations evident widely across
      mammalian species. For instance, adolescent rats, like their human counterparts,
      exhibit elevations in peer-directed social interactions, risk-taking/novelty
      seeking and drug and alcohol use relative to adults, along with notable changes
      in motivational and reward-related brain regions. After reviewing these topics,
      the present paper discusses conditioned preference and aversion data showing
      adolescents to be more sensitive than adults to positive rewarding properties of
      various drugs and natural stimuli, while less sensitive to the aversive
      properties of these stimuli. Additional experiments designed to parse specific
      components of reward-related processing using natural rewards have yielded more
      mixed findings, with reports of accentuated positive hedonic sensitivity during
      adolescence contrasting with studies showing less positive hedonic affect and
      reduced incentive salience at this age. Implications of these findings for
      adolescent substance abuse will be discussed.

PMID- 19762141
TI  - Management of asymptomatic mid-trimester lower segment scar dehiscence.

PMID- 19762142
TI  - Isolation and differentiation of nestin positive cells from rat oral mucosal
      lamina propria.
AB  - Despite successes in the isolation and characterization of stem cells from the
      oral mucosal epithelium, there have been few studies on progenitor cells from the
      oral mucosal lamina propria. In this study, we isolate rat oral mucosal lamina
      propria cells (OMLPC) using nestin as a marker in an immunomagnetic sorting
      technique. The OMLPCs was negative for cytokeratin. Nestin and vimentin were
      expressed in the OMLPCs. And CD44 and STRO-1 were expressed in a subset of the
      OMLPCs, which suggest that the nestin positive OMLPCs be heterogeneous.
      Otherwise, OMLPCs express Oct4, which is a critical gene for pluripotency. The
      OMLPCs proliferated actively in vitro. A colony forming study demonstrated that
      OMLPCs exhibited colony-generating capacity. When cultured in defined medium,
      OMLPCs generated cells characteristic of osteoblast, adipocyte and astrocyte-like
      cells. In addition, OMLPCs seeded into three dimensional scaffolds form bone-like
      structures in vivo after 8 weeks. All of the results demonstrate that OMLPCs are
      a population of mesenchymal progenitor cells existing in rat oral mucosal lamina
      propria. Nestin is shown to be a useful molecular marker for these cells. In
      certain environments, OMLPCs can form hard tissue. Thus, OMLPCs may serve as a
      suitable source of cells for future bone or tooth tissue engineering
      applications.

PMID- 19762143
TI  - The selection of patients for active surveillance: could it be perfect?

PMID- 19762144
TI  - Predicting recurrence and progression of noninvasive papillary bladder cancer at
      initial presentation based on quantitative gene expression profiles.
AB  - BACKGROUND: Currently, tumor grade is the best predictor of outcome at first
      presentation of noninvasive papillary (Ta) bladder cancer. However, reliable
      predictors of Ta tumor recurrence and progression for individual patients, which
      could optimize treatment and follow-up schedules based on specific tumor biology,
      are yet to be identified. OBJECTIVE: To identify genes predictive for recurrence
      and progression in Ta bladder cancer at first presentation using a quantitative,
      pathway-specific approach. DESIGN, SETTING, AND PARTICIPANTS: Retrospective study
      of patients with Ta G2/3 bladder tumors at initial presentation with three
      distinct clinical outcomes: absence of recurrence (n=16), recurrence without
      progression (n=16), and progression to carcinoma in situ or invasive disease
      (n=16). MEASUREMENTS: Expressions of 24 genes that feature in relevant pathways
      that are deregulated in bladder cancer were quantified by real-time polymerase
      chain reaction on tumor biopsies from the patients at initial presentation.
      RESULTS AND LIMITATIONS: CCND3 (p=0.003) and HRAS (p=0.01) were predictive for
      recurrence by univariate analysis. In a multivariable model based on CCND3
      expression, sensitivity and specificity for recurrence were 97% and 63%,
      respectively. HRAS (p<0.001), E2F1 (p=0.017), BIRC5/Survivin (p=0.038), and
      VEGFR2 (p=0.047) were predictive for progression by univariate analysis.
      Multivariable analysis based on HRAS, VEGFR2, and VEGF identified progression
      with 81% sensitivity and 94% specificity. Since this is a small retrospective
      study using medium-throughput profiling, larger confirmatory studies are needed.
      CONCLUSIONS: Gene expression profiling across relevant cancer pathways appears to
      be a promising approach for Ta bladder tumor outcome prediction at initial
      diagnosis. These results could help differentiate between patients who need
      aggressive versus expectant management.

PMID- 19762146
TI  - Use of fly ash, phosphogypsum and red mud as a liner material for the disposal of
      hazardous zinc leach residue waste.
AB  - Increasing amounts of residues and waste materials coming from industrial
      activities in different processes have become an increasingly urgent problem for
      the future. The release of large quantities of heavy metals into the environment
      has resulted in a number of environmental problems. The present study
      investigated the safe disposal of the zinc leach residue waste using industrial
      residues such as fly ash, phosphogypsum and red mud. In the study, leachability
      of heavy metals from the zinc leach residue has been evaluated by mine water
      leaching procedure (MWLP) and toxicity characteristic leaching procedure (TCLP).
      Zinc removal from leachate was studied using fly ash, phosphogypsum and red mud.
      The adsorption capacities and adsorption efficiencies were determined. The
      adsorption rate data was analyzed according to the pseudo-second-order kinetic,
      Elovich kinetic and intra-particle diffusion kinetic models. The pseudo-second
      order kinetic was the best fit kinetic model for the experimental data. The
      results show that addition of fly ash, phosphogypsum and red mud to the zinc
      leach residue drastically reduces the heavy metal content in the leachate and
      could be used as liner materials.

PMID- 19762145
TI  - Macrophage migration inhibitory factor anti-thrombin III complexes are decreased
      in bladder cancer patient serum: Complex formation as a mechanism of
      inactivation.
AB  - Mounting evidence suggests that the pro-inflammatory cytokine macrophage
      migration inhibitory factor (MIF) may serve as an important link between chronic
      inflammation and carcinogenesis as evidenced by the increase in serum MIF found
      in patients with various cancers. The present study identifies anti-thrombin III
      (ATIII) as an endogenous MIF binding protein, which reduces MIF biological
      activity. Serum MIF in bladder cancer patients (TCC stage II, n=50) was increased
      when compared to normal patients (n=50), while ATIII-MIF complexes were decreased
      in bladder cancer patient serum. These data suggest that increased circulating
      levels of bioactive MIF are present in bladder cancer patient serum.

PMID- 19762147
TI  - An emerging pollutant contributing to the cytotoxicity of MSWI ash wastes:
      strontium.
AB  - In this study, we used the multiple toxicity characteristic leaching procedure to
      test the long-term leaching behavior of bottom ash, scrubber residue, and
      baghouse ash from a municipal solid waste incinerator (MSWI). We used the short
      term viability percentage of African green monkey kidney cells (Vero cells) as a
      bioindicator to investigate the cytotoxicity of the leachates from the MSWI ash
      wastes. We found that strontium was a significant contributor to the cytotoxicity
      of the bottom ash.

PMID- 19762148
TI  - The stability of arsenic and selenium compounds that were retained in limestone
      in a coal gasification atmosphere.
AB  - The aim of this work was to evaluate the stability of arsenic and selenium
      species retained in a lime/limestone mixture obtained by using limestone as a
      sorbent for gas cleaning in a coal gasification atmosphere. It was found that the
      stability of arsenic and selenium species produced by the gas-solid reactions
      with lime/limestone may be affected by their exposure to air and by their contact
      with water. The results confirm the conclusions of a previous work in which
      Ca(AsO(2))(2) and CaSe was postulated as the products of the reaction between the
      arsenic and selenium species present in a coal gasification atmosphere with
      lime/limestone. Moreover it was proved that the compounds (Ca(AsO(2))(2) and
      CaSe) may undergo transformations when the sorbents post-retention are stored or
      disposed of in air. From the results obtained by XAFS it was possible to identify
      the Ca(3)(AsO(4))(2) produced by the oxidation of the Ca(AsO(2))(2) on the
      sorbent surface. The XAFS results for selenium showed that the CaSe formed on the
      sorbent was transformed to form several species, but mainly elemental Se. These
      changes in the speciation of arsenic and selenium may explain the behavior of the
      sorbent post-retention during the water solubility test. Although the selenium
      compounds and the products that may originate from their decomposition in water
      are not toxic, in the case of arsenic, species like Ca(AsO(2))(2) and
      Ca(3)(AsO(4))(2) may lixiviate, and generate toxic arsenic compounds in solution
      that could pose a risk when the sorbent is finally disposed of.

PMID- 19762149
TI  - Application of response surface methodology for optimization of peroxi
      coagulation of textile dye solution using carbon nanotube-PTFE cathode.
AB  - The decolorization of C.I. Basic Yellow 2 (BY2) by peroxi-coagulation process
      based on carbon nanotube-PTFE electrode as cathode was studied in a batch
      reactor. Response surface methodology (RSM) was employed to assess individual and
      interactive effects of the four main independent parameters (electrolysis time,
      initial pH, applied current and initial concentration of the dye solution) on the
      decolorization efficiency. A central composite design (CCD) was employed for the
      optimization of peroxi-coagulation treatment of BY2. A second-order empirical
      relationship between the response and independent variables was derived. Analysis
      of variance (ANOVA) showed a high coefficient of determination value
      (R(2)=0.949). Maximum decolorization efficiency was predicted and experimentally
      validated. The optimum electrolysis time, initial pH, applied current and initial
      dye concentration were found to be 16 min, 3, 200 mA and 15 mg l(-1),
      respectively. Under the optimum conditions established, high decolorization
      (>95%) was experimentally obtained for BY2. This study clearly showed that
      response surface methodology was one of the suitable methods to optimize the
      operating conditions. Graphical response surface and contour plots were used to
      locate the optimum point.

PMID- 19762150
TI  - Degradation characteristics of humic acid over iron oxides/Fe 0 core-shell
      nanoparticles with UVA/H2O2.
AB  - Iron oxides coated on Fe(0) core-shell nanospheres (nIOCI) were synthesized
      through the reduction of ferrous sulfate aqueous solution by sodium borohydride
      at ambient atmosphere. The catalyst was highly effective for the degradation of
      humic acid (HA) in the presence of H(2)O(2) and UVA at neutral pH. Under
      deoxygenated conditions in the dark, the generation of hydroxyl radicals in
      aqueous nIOCI dispersion verified its galvanic cell-like performance, which
      enhanced the interfacial electron transfer and led to its higher reactivity. By
      the total organic carbon, the absorbance of UV(254), FTIR, the molecular weight
      distribution and the chemical fractional character analysis, the degradation
      process of HA was shown to proceed by the disappearance of aromaticity, the
      increase of hydrophilic fraction and aromatic ring openings into CO(2) and small
      organic acid. The treated HA showed much lower reactivity toward chlorine and the
      disinfection byproduct (DBP) formation potential was also greatly reduced.
      Moreover, it was found that the DBP formation potential more depended on the
      structure of the intermediates of HA degradation than TOC removal.

PMID- 19762151
TI  - On the definitions and physiology of back pain, referred pain, and radicular
      pain.

PMID- 19762153
TI  - Analgesic efficacy of tramadol, pregabalin and ibuprofen in menthol-evoked cold
      hyperalgesia.
AB  - We investigated the analgesic efficacy of single doses of ibuprofen, tramadol and
      pregabalin in menthol-evoked cold pain in a randomized, placebo-controlled four
      way cross-over study in 20 healthy volunteers. Tramadol 100mg significantly
      reduced menthol-evoked cold hyperalgesia. Effects of ibuprofen 600mg and
      pregabalin 100mg were not significant. Analgesic effects of tramadol were
      associated with minor side effects, particularly fatigue and nausea. Minor side
      effects also accompanied analgesic effects of pregabalin and ibuprofen in
      subjects responding to these drugs, mostly fatigue, dizziness and difficulties to
      concentrate for pregabalin and gastric upset for ibuprofen. Five out of 18
      subjects had a 50% reduction of cold hyperalgesia with tramadol, three of these
      additionally responded to pregabalin, and two with all three drugs. The numbers
      needed to treat (NNT >or= 50% for tramadol 4.5, for pregabalin 9) largely agree
      with the reported efficacy of tramadol and of moderate dosages of pregabalin in
      patients with peripheral or central neuropathic pain suggesting that menthol
      evoked cold pain hypersensitivity may represent a valid model for neuropathic
      pain, particularly cold allodynia.

PMID- 19762154
TI  - Management of unfit patients with unfavourable non-Hodgkin's lymphomas.
AB  - Lymphoma is a malignant disease that often occurs in elderly patients. Although
      many treatment options are available, comorbidities and limitations of functional
      reserves limit their use in frail patients. Still, because of the high
      sensitivity of disease to these treatments, even reduced doses and schedules may
      allow long-term disease control or even cure. The question that remains is how to
      use these treatments while controlling risks. Fortunately, both biological and
      clinical researches allow for progress that will help clinicians improve
      treatment strategies. During the last years, interest for research in the elderly
      with lymphoma has increased. Most of it concerned fit patients but not only.
      Among those, availability of specific monoclonal antibodies, which improve
      treatment efficiency without significantly increasing toxicity, appears as a
      major step forward which should be further developed. Yet, recent data has also
      been published on other topics including trials on frail patients and specific
      biological data. Early evaluation of response is also among important topics
      which should be scrutinized. Overall, recently published results raise hopes for
      future management of our patients and more is expected soon.

PMID- 19762155
TI  - Anticoagulation therapy for prevention and treatment of venous thromboembolic
      events in cancer patients: a review of current guidelines.
AB  - Cancer patients in general have a high risk of venous thromboembolic events (VTE)
      driven not only by patient-related risk factors, but also risk factors related to
      the disease and anti-cancer therapies. Cancer patients with documented VTE have a
      notably worse outcome than non-cancer VTE patients. Since VTE is a highly
      preventable condition, it is striking that large surveys have shown significant
      underuse of VTE prophylaxis in surgical cancer patients and in medical cancer
      patients in particular. Recently, guidelines have been issued from European and
      American medical oncology societies and organizations for identification of
      cancer patients at risk, and the guidelines give recommendations for treatment of
      individual groups of cancer patients. This review summarizes the recommendations
      for VTE prophylaxis and treatment from the recent guidelines and reviews some
      outstanding issues in VTE prophylaxis and treatment of cancer patients.

PMID- 19762156
TI  - Management of primary and advanced breast cancer in older unfit patients (medical
      treatment).
AB  - Elderly women constitute a large group of breast cancer patients, and after
      multidimensional geriatric assessment (MGA) only a minor part of them are found
      in perfect health (=fit), while the remaining display one or more physical or
      functional limitations or familial/social problems and are therefore categorized
      as vulnerable or frail (=unfit). Although randomized trials have not produced
      modest evidence that surgery impacts on ultimate survival of elderly women with
      hormone-responsive tumors, there is a general consensus that age alone should not
      prevent surgical local treatment even in unfit women due to the limited morbidity
      of breast surgery and to the risk of local progression. Activity and safety of
      AIs appear comparable in elderly women compared to younger counterparts, although
      concomitant cardiovascular comorbidity and osteoporosis should be closely
      monitored. Of note, compliance to oral therapy in unfit women and possible
      interferences with concomitant medications are still poorly documented issues.
      With the exception of high-risk node positive and estrogen-receptor negative
      patients, administration of adjuvant chemotherapy for estrogen-receptor positive
      unfit patients is rarely recommended since the uncertain gain in relapse-free
      survival is exceeded by the increased risk of toxicity and competitive causes of
      death. Endocrine-responsive metastatic disease is managed with one or more lines
      of endocrine treatment as in younger patients. Single agent sequential
      chemotherapy regimens are to be preferred to combination regimens, which are
      usually more toxic with a limited survival gain even in younger patients. When
      and how dose reductions should be applied to unfit patients is highly
      controversial. Trastuzumab in association with chemotherapy can be administered
      to elderly patients presenting HER2 overexpressing tumors, although the risk of
      cardiac adverse events in unfit patients is largely unknown. Bevacizumab-based
      combinations increase the activity and also toxicity of taxane chemotherapy, and
      are not a preferred option.

PMID- 19762157
TI  - Abnormal behavioral and neurotrophic development in the younger sibling receiving
      less maternal care in a communal nursing paradigm in rats.
AB  - Maternal behavior in rodents has been proposed to vary as a function of the
      external environment and, in turn, adjust offspring's stress and fear responses.
      Early handling (brief periods of maternal separation during the first two weeks
      of life) studies and analyses of spontaneously high-caring rat mothers converge
      to indicate that increased levels of maternal care may reduce offspring
      emotionality in adulthood. However, the hypothesis that environment-dependent
      reduction in maternal care correlates with increased offspring vulnerability to
      pathology has been scarcely investigated. To test this hypothesis we studied
      maternal care and offspring development in young, adolescent and young-adult
      Sprague-Dawley rats reared in a communal nursing situation, characterized by two
      dams delivering their offspring four days apart and communally caring for them
      until weaning. We show that dams of the first-born litter show increased
      aggression towards the pregnant female and that offspring belonging to the second
      born litter receive less maternal care compared to older cage-mates.
      Additionally, second-born rats show increased anxiety-related behavior in a plus
      maze test in adolescence and adulthood and abnormal developmental trajectories in
      terms of social interaction and BDNF levels in the amygdala and hippocampus
      compared to both the first-born litter and to animal facility reared controls.
      This is the first indication that adverse environments, not requiring
      experimenter handling, may reduce maternal care and in turn increase offspring's
      emotionality and modify social behavior and BDNF developmental trajectories.

PMID- 19762158
TI  - What constitutes too long of a delay? Determining the cortisol awakening response
      (CAR) using self-report and PSG-assessed wake time.
AB  - The cortisol awakening response (CAR) is a burst of cortisol in response to
      awakening from sleep that is superimposed on the circadian rhythm of cortisol.
      Determination of the CAR is contingent on the timing of sample collection: a
      delay between waking and collection of the first sample may affect the rise of
      the CAR, and could explain equivocal findings reported in the literature. We
      evaluated the impact of a delay between wake time and collection of waking
      cortisol samples on the CAR. Two methods were used to identify wake time:
      polysomnography (PSG) and self-report (S-R). Participants (total n=207, mean age
      74.0+/-7.2 years) included bereaved older adults (n=35), caregivers (n=50),
      patients with insomnia and co-morbid medical disorders (n=68), and the healthy
      older adults (n=54). We used ANOVA to test if a delay >15 min affected the CAR.
      We also fitted cubic spline models to assess expected cortisol levels, the
      expected CAR, and the expected decrease in CAR. Wake times measured by PSG and S
      R did not differ significantly. Large delays were observed (for both PSG and S-R)
      between wake time and collection of the waking cortisol sample (24.8+/-32.2 min
      for PSG and 28.3+/-49.2 min for S-R). Both statistical methods indicated that a
      delay >15 min between wake time and first cortisol sample collection
      significantly affected the CAR (p's<.005); later collection times were associated
      with smaller CAR values. Later collection times and reduced CAR values may affect
      the interpretation of clinical associations. Our data also show that S-R
      assessments of wake time perform equally well to PSG for evaluating adherence
      with CAR sampling procedures.

PMID- 19762159
TI  - Hormonal responses to the 5-HT1A agonist buspirone in remitted endogenous
      depressive patients after long-term imipramine treatment.
AB  - INTRODUCTION: The serotonin-1A (5-HT1A) receptor subtypes are considered as
      targets of a variety of antidepressant drugs. Previous studies have suggested
      different adaptive changes in pre- and post-synaptic 5-HT receptors in the brain
      after treatment with non-selective tricyclic antidepressants (TCA) and selective
      5-HT re-uptake inhibitors (SSRIs). The present study aimed to investigate the
      adaptive effect of the TCA imipramine on the post-synaptic 5-HT1A receptor
      function in the hypothalamus. METHODS: A longitudinal design was used in 14
      patients with major depressive disorder (DSM-IV) with endogenous features
      (Newcastle Scale) in order to assess the functional status of post-synaptic 5
      HT1A receptors before and after successful antidepressant treatment with
      imipramine. The effect of the 5-HT1A receptor agonist, buspirone, on ACTH,
      cortisol, and prolactine (PRL) plasma levels was used to assess the functional
      status of hypothalamic 5-HT1A receptors. A group of 15 concurrent normal subjects
      were used as control. RESULTS: Endogenous depressed patients in remission and
      currently receiving treatment with imipramine (mean length of treatment 145 days,
      SD=27) presented significantly lower buspirone responses to ACTH and cortisol
      than in the pre-treatment condition (Deltamax p< or =.05; AUC p<.001) and to ACTH
      in comparison with healthy controls (Deltamax p<.01; AUC p<.05). No significant
      differences were found between the post-treatment and pre-treatment PRL
      responses, or between patients in both conditions and controls; nevertheless, the
      PRL response in patients in remission and receiving treatment almost reached the
      values seen in controls. CONCLUSIONS: This study extends previous findings from
      our group using the SSRI citalopram as an antidepressant. Imipramine and
      citalopram induce similar changes in the endocrine response to buspirone in
      depressed patients. As the direction of change in ACTH-cortisol and PRL responses
      after treatment is the opposite, we cannot substantiate increases or decreases in
      the sensitivity of post-synaptic 5-HT1A receptors in the hypothalamus by long
      term imipramine treatment and/or resolution of illness. Therefore, the hormonal
      changes may result from different or multiples unknown mechanisms.

PMID- 19762160
TI  - Not only anticancer drugs but also enzymes can be encapsulated in either micelle
      or other carrier for the treatment of cancer.

PMID- 19762161
TI  - Electrical stimulation of the olfactory mucosa: an alternative treatment for the
      temporal lobe epilepsy?
AB  - Epilepsy threatens the health of more than 50 million people all over the world.
      The temporal lobe epilepsy (TLE) is one of the most common forms of epilepsy and
      still is one of the commonest drug-resistant epilepsies (so called refractory
      epilepsy). Vagus nerve stimulation (VNS) was the first non-pharmaceutical therapy
      used for the treatment of medically refractory partial onset seizures in 1997,
      but its more extensive application was hampered by its high cost and side
      effects. It had been suggested that olfactory stimulation with chemical products
      was likely to lead to widespread de-synchronization, akin to VNS in exercising
      its seizure-reducing property. But it is hard to control the "dosage" of
      olfactory stimulation with chemical products and the awful feelings caused by
      chemicals made it difficult to clinic practice. Here we propose an alternative
      method, electric stimulation to the olfactory mucosa for the treatment of TLE.
      Different from VNS, a tiny electrode for the stimulation will be minimized into a
      dimension small enough to fix into nasal cavity and attached to the olfactory
      mucosa through a nostril in current proposal, so the side effects of VNS caused
      by operation will be totally avoided. Based on data from related researches, we
      believe that current therapy we propose here may be a safe and efficient
      treatment for TLE in the future.

PMID- 19762162
TI  - Sequence-based genotyping HPV L1 DNA and RNA transcripts in clinical specimens.
AB  - We developed a direct sequence-based genotyping method to detect single and
      multiple HPV L1 DNA and RNA types in genital and dermatological specimens. Our
      method couples PCR amplification of a highly conserved HPV L1 segment using a
      broad spectrum-generic primer cocktail mix with automated sequencing of amplified
      PCR products, followed by GenBank sorting of sequencing data. We genotyped 5 skin
      and 30 cervical HPV DNA-positive specimens using this method and established its
      first experimentally derived working cutoff value with the aid of commercial
      hybridization-based techniques. We suggest that sequence-based genotyping of
      appropriately amplified DNA and RNA products may serve as a primary HPV detection
      method in dermatological specimens. It can be applied as an all-purpose
      genotyping method for rare HPV types not detectable by commercial hybridization
      based techniques and for sorting multiple HPV infections by order of prevalence.

PMID- 19762163
TI  - Vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9),
      and thrombospondin-1 (TSP-1) expression in urothelial carcinomas.
AB  - Angiogenesis is a multistep process that depends on the balance of proangiogenic
      factors and inhibitors as well as on interactions with the extracellular matrix.
      We examined the immunohistochemical expression of the defining angiogenic agents,
      vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9),
      and the antiangiogenic agent thrombospondin-1 (TSP-1) in 131 patients with
      urothelial carcinoma and correlated their expression levels with
      clinicopathological parameters. VEGF and MMP-9 expression was higher in high
      grade tumors than in low-grade tumors (p=0.000 and p=0.001, respectively),
      whereas the reverse was true for TSP-1 (p=0.000). VEGF and MMP-9 expression was
      higher in deeper tumors compared to superficial tumors and in invasive tumors
      compared to non-invasive tumors (p=0.001 and p=0.001, respectively), while TSP-1
      was lower (p=0.000). We could differentiate 22 of 41 muscle-invasive (T2) cases
      as superficial (T2a; n=7) or deep (T2b; n=15), but no difference was found
      between them regarding VEGF, MMP-9, or TSP-1 expression (p=0.783, p=0.289, and
      p=0.783, respectively). There was a positive correlation between VEGF and MMP-9
      expression (p=0.008, r=0.23) but a negative correlation between MMP-9 and TSP-1
      expression (p=0.014, r=-0.21). Increased VEGF and MMP-9 expression as well as
      decreased TSP-1 expression may play considerable roles in the invasion and
      differentiation of urothelial carcinoma.

PMID- 19762164
TI  - Biomechanical comparison of techniques to reduce the bulk of lacerated flexor
      tendon ends within digital sheaths of the porcine forelimb.
AB  - PURPOSE: Zone II flexor tendon repairs may create a bulging effect with increased
      bulk and resistance to tendon gliding. A biomechanical time 0 study was performed
      to assess 2 methods of tendon antibulking for work of flexion and strength
      characteristics. METHODS: We placed 24 fresh-frozen porcine forelimb tendons in a
      custom jig. Deep flexor tendon was sectioned just distal to the intact A1 and A2
      pulleys. Specimens were divided into 3 groups before repair: group 1, nonmodified
      tendon; group 2, 30 degrees bilateral notch excised from both tendon ends; and
      group 3, triangular longitudinal central wedge excised from both tendon ends. All
      repairs used a 4-strand modified Kessler core suture and running circumferential
      epitendinous suture. Work of flexion, 2-mm gap formation, and ultimate load to
      failure were tested. RESULTS: Both antibulking techniques (groups 2 and 3) had
      significantly less work of flexion than group 1 (36.3 and 34.9 J vs 142.9 J, p <
      .001). There was no significant change in work of flexion between groups 2 and 3
      (p > .05). There was no significant difference in terms of 2-mm gap formation
      among the 3 groups (p > .05). Groups 1 and 3 exhibited a significantly higher
      load to failure compared with group 2 (p < .05). CONCLUSIONS: The antibulking
      repair techniques used in this study decrease the work of flexion with no
      significant change in force to 2-mm gap formation. Group 2, however, did have
      significantly lower load to failure. These techniques might be beneficial in zone
      II flexor tendon injury, in which the tight annular pulley system restricts
      tendon gliding. However, this is a time 0 study and the potential adverse effects
      of increase tendon manipulation and trauma were not analyzed, which might
      increase adhesions and scar during the healing phase of tendon repair.

PMID- 19762165
TI  - Palmar abduction measurements: reliability and introduction of normative data in
      healthy children.
AB  - PURPOSE: Previously, we studied normative and reliability data of palmar thumb
      abduction measurements (conventional goniometry, the Pollexograph thumb, the
      Pollexograph metacarpal, the Inter Metacarpal Distance, the American Society of
      Hand Therapists method, and the American Medical Association method) in healthy
      adults. Because many interventions aiming to improve palmar abduction are
      performed at an early age, the goal of this study was to assess normative and
      reliability data of these measurement methods in children. METHODS: We performed
      measurements with the Pollexograph thumb, the Pollexograph metacarpal and Inter
      Metacarpal Distance in 100 healthy children to acquire normative data. A retest
      was performed in 63 children to assess intraobserver reliability. RESULTS: Mean
      active and passive palmar abduction measured with the Pollexograph thumb was 62
      degrees (range, 40 degrees to 76 degrees). The range of motion of the
      Pollexograph metacarpal was smaller (mean 49 degrees, range, 32 degrees to 64
      degrees). The mean Inter Metacarpal Distance was 50 mm (range, 36-70 mm).
      Intraclass correlation coefficients of the Pollexograph thumb, Pollexograph
      metacarpal, and Inter Metacarpal Distance indicated excellent reliability
      (intraclass correlation coefficients between 0.85 and 0.92). CONCLUSIONS:
      Normative Pollexograph thumb and Pollexograph metacarpal data showed that means
      measured in children are comparable to values found in healthy adults.
      Reliability data indicated that the Pollexograph thumb, the Pollexograph
      metacarpal, and Inter Metacarpal Distance are also reliable measurement methods
      in children.

PMID- 19762166
TI  - Occurrence of central polydactyly, syndactyly, and cleft hand in a single family:
      report of five hands in three cases.
AB  - Central polydactyly, syndactyly, and cleft hand are categorized separately in the
      International Federation of Societies for Surgery of the Hand classification.
      However, some investigators have proposed that these malformations should be
      classified into a single category: abnormal induction of finger rays. In this
      article, we report 5 hands with central polydactyly, syndactyly, and cleft hand
      in 3 patients from the same family and discuss the phenotypes in each hand.

PMID- 19762167
TI  - Prenatal diagnosis and prognosis of triple X syndrome: 47, XXX.
AB  - Triple X syndrome is a relatively common sex chromosomal abnormality occurring in
      0,1% of live-born female infants. Most of these infants have a normal phenotype
      and only a few cases with 47, XXX karyotype have congenital malformations. We
      report three cases of triple X syndrome that were diagnosed prenatally by genetic
      amniocentesis for advanced maternal age and have been observed from birth to age
      of 3 to 12 years. A description of their growth and development is presented. The
      birth weight was normal in all patients and one of them had facial dysmorphism
      with right microphtalmia and auricular septal defect. During the first 2 years of
      life, the neuromotor development of these infants was not distinguishable from
      chromosomally normal children. By 3 years of age, two patients have a moderate
      developmental delay in speech and language. One girl 12-year-old had normal
      schooling. The diagnosis of the triple X syndrome can be never made because
      clinical demonstrations are not rather important to arouse the demand of a
      karyotype. Prenatal diagnosis is often made in front of the advanced maternal
      age. Expectant parents must be counseled as to the significance of this 47, XXX
      karyotype and prognostic information must be given.

PMID- 19762168
TI  - [Pseudo-HELLP or... true HELLP and pseudo-thrombotic microangiopathies?].

PMID- 19762169
TI  - Zoonotic mosquito-borne flaviviruses: worldwide presence of agents with proven
      pathogenicity and potential candidates of future emerging diseases.
AB  - An update on the mosquito-borne flavivirus species including certain subtypes, as
      listed in the Eighth Report of the International Committee on Taxonomy of
      Viruses, is given. Special emphasis is placed on viruses which have been shown to
      cause diseases in animals, and viruses for which no pathogenicity has been proven
      yet. Several recent examples (Usutu virus and lineage-2 West Nile virus in
      central Europe, Zika virus in Micronesia) have shown that sources providing
      information on such scientifically largely neglected viruses are valuable tools
      for scientists and public health officials having to deal with such disease
      emergences. Furthermore the effects of global warming will lead to introduction
      of competent mosquito vectors into temperate climate zones and will increase
      efficiency of viral replication in less competent vector species. This,
      facilitated by rising global travel and trade activities, will facilitate
      introduction and permanent establishment of mosquito-borne viruses, some of which
      may become of public health or veterinary concern, into novel environments, e.g.
      industrialized countries worldwide.

PMID- 19762170
TI  - The birth of consciousness.
AB  - Newborn infants fulfil some criteria of being conscious i.e. being aware of the
      body, the self and the world. They are able to differentiate between self and
      nonself touch, express emotions and show signs of shared feelings. They process
      sensory impressions including pain at a cortical level. They remember rhythmic
      sounds and vowels which they have been exposed to during fetal life. The
      spontaneous resting activity discovered in the cortex of newborn infants may
      correspond to what William James called "the stream of consciousness".

PMID- 19762171
TI  - The management of endotracheal tubes and nasal cannulae: the role of nurses.
AB  - The management of endotracheal tubes and nasal cannulae covers a large part of
      work time of nurses involved in the care of very preterm infants. These
      procedures, although continuously performed, have not yet been scientifically
      demonstrated. In fact, there is limited evidence regarding several points such as
      the frequency of endotracheal suctioning, the level of suction pressure, the
      duration of suctioning, the depth of catheter insertion, the sterility, and the
      use of normal saline during endotracheal suction. With regard to the nasal
      cannulae, there is a more recent use of this device consisting in delivering end
      expiratory pressure or gas flow to reduce the frequency of apneas and
      desaturations in preterm infants or for the management of RDS. This approach is
      defined high-flow nasal cannulae (HFNC). In this article, we review the
      literature on the airway management of intubated patients as well as of infants
      managed with nasal-CPAP or nasal cannulae. Potential fields of research on this
      topic are suggested.

PMID- 19762172
TI  - Human milk fortifiers in very low birth weight infants.
AB  - The use of HMF remains an important option and has become common practice in all
      neonatal intensive care units. However, optimal composition of fortifiers is
      still undefined and more data are needed on safety and long-term benefits.
      Further research should be directed toward comparisons between different
      proprietary preparations, evaluating both short-term and long-term outcomes and
      adverse effects, in search of the best method of fortification.

PMID- 19762173
TI  - Genetic forms of hypopituitarism and their manifestation in the neonatal period.
AB  - The anterior pituitary gland is a central regulator of growth, reproduction and
      homeostasis. The development of the pituitary gland depends on the sequential
      temporal and spatial expression of transcription factors and signalling
      molecules. Naturally occurring and transgenic murine models have demonstrated a
      role for many of these molecules in the aetiology of congenital hypopituitarism.
      These include the transcription factors HESX1, PROP1, POU1F1, LHX3, LHX4, PITX1,
      PITX2, OTX2, SOX2 and SOX3. Mutations in any of the genes involved in pituitary
      development may result in congenital hypopituitarism, which manifests as the
      deficiency in one or more pituitary hormones. The phenotype can be highly
      variable and may consist of isolated hypopituitarism, or more complex disorders
      such as septo-optic dysplasia (SOD) and holoprosencephaly. Neonates with
      congenital hypopituitarism may present with non-specific symptoms, with or
      without associated developmental defects such as ocular, midline and genital
      abnormalities. Alternatively, they may be initially asymptomatic but at risk of
      developing pituitary hormone deficiencies over time. The overall incidence of
      mutations in known transcription factors in patients with hypopituitarism is low,
      indicating that many genes remain to be identified. Their characterization will
      further elucidate the pathogenesis of this complex condition and will shed light
      on normal pituitary development.

PMID- 19762174
TI  - Initial nutritional management of the preterm infant.
AB  - Postnatal nutrition has a large impact on long-term outcome of preterm infants.
      Evidence is accumulating showing even a relationship between nutrient supply in
      the first week of life and later cognitive development in extremely low birth
      weight infants. Since enteral nutrition is often not tolerated following birth,
      parenteral nutrition is necessary. Yet, optimal parenteral intakes of both energy
      and amino acids are not well established. Subsequently, many preterm infants fail
      to grow well, with long-term consequences. Early and high dose amino acid
      administration has been shown to be effective and safe in very low birth weight
      infants, but the effect of additional lipid administration needs to be defined.

PMID- 19762175
TI  - The pacifier debate.
AB  - A variety of studies have indicated that pacifier use lowers the risk of SIDS.
      Many observational studies have demonstrated a negative association between
      pacifier use and breastfeeding duration. However, observational studies cannot be
      used to determine whether the pacifier is the real cause of breastfeeding
      cessation. Evidence for causation can be better supplied by randomised controlled
      trials (RCTs). Three RCTs have been conducted on the relationship between
      pacifiers and breastfeeding, but each study has limitations, implying that the
      evidence of not causal effect can be questionated. We have recently presented the
      results of a large RCT which demonstrated that in mothers who are successfully
      breastfeeding at 2 weeks, the recommendation to offer a pacifier does not modify
      the prevalence of exclusive and any breastfeeding at different ages or the
      duration of lactation. It is therefore important that lactation consultants and
      international agencies reexamine their staunch position to discourage the use of
      pacifiers on the basis of a supposed adverse effect on the success and duration
      of breastfeeding.

PMID- 19762176
TI  - Hypothermia for hypoxic ischemic encephalopathy in infants > or =36 weeks.
AB  - Hypoxic ischemic encephalopathy is a serious condition affecting infants which
      can result in death and disability. This is a summary of pathogenesis of HIE,
      animal studies of cooling for hypoxic and ischemic models, human hypothermia
      trials, and the American Academy of Pediatrics publication on hypothermia for
      HIE. Hypothermia for neonatal HIE is continuing to evolve as a therapy. Studies,
      gaps in knowledge and opportunities for research are presented herein.

PMID- 19762177
TI  - Cholesterol-loaded-cyclodextrins and fertility potential of stallions
      spermatozoa.
AB  - Irreversible damage occurs to spermatozoal membranes, during the phase
      transition, when spermatozoa are cooled from room temperature to 5 degrees C.
      Some of this damage can be ameliorated by adding cholesterol to the membrane,
      thereby altering membrane lipid composition. Adding cholesterol-loaded
      cyclodextrins (CLCs) to stallion spermatozoa prior to freezing, increases cell
      cryosurvival. However, the fertilizing potential of CLC-treated stallion
      spermatozoa is unknown. To address this, experiments were conducted which
      evaluated the ability of CLC-treated stallion spermatozoa to capacitate, acrosome
      react, and bind to the zona pellucida in vitro, and to fertilize oocytes in vivo.
      When CLC-treated cryopreserved stallion spermatozoa were treated with various
      agents to induce capacitation and the acrosome reaction (AR),
      dilauroylphosphatidylcholine (PC-12) and lysophosphatidylcholine (LPC) induced
      the AR in control cells (62% and 55%, respectively) but not in CLC-treated cells
      (17% and 14%, respectively, P<0.05). However, the calcium ionophore A23187
      induced the AR in both control- and CLC-treated cells equally well (39%, P>0.05).
      Control- and CLC-treated stallion spermatozoa bound to ZP of cattle oocytes
      equally well (0.44+/-0.16 vs. 0.25+/-0.09, respectively; P>0.05). In addition,
      the fertility rates of mares inseminated with control- and CLC-treated sperm were
      similar (P>0.05).

PMID- 19762178
TI  - Dystocia in 3-year-old beef heifers; relationship to maternal nutrient intake
      during early- and mid-gestation, pelvic area and hormonal indicators of placental
      function.
AB  - The influence of nutrition during the first and second trimesters of gestation on
      the occurrence of dystocia was investigated in 3-year-old composite-breed beef
      heifers. Heifers were allocated according to stratification by weight and
      genotype to either a high (H/-=76 MJ metabolisable energy (ME) and 1.4 kg crude
      protein (CP)), or low (L/-=62 MJ ME and 0.4 kg CP daily) nutritional treatment on
      the day of artificial insemination (day 0) to the same Senepol bull. Half of each
      nutritional group changed to an opposite nutritional group on day 93 of gestation
      (-/H=82 MJ ME and 1.4 kg CP; -/L=63 MJ ME and 0.4 kg CP daily), resulting in four
      treatment groups: HH (n=16); HL (n=19); LH (n=17); LL (n=19). From 180 days until
      calving all heifers were fed the same diets. Pelvic area measures were taken at
      heifer selection (-72 days) and at 117 days. Maternal circulating concentrations
      of estrone sulphate (ES), bovine placental lactogen (bPL), bovine pregnancy
      associated glycoprotein and progesterone were monitored throughout gestation.
      Heifers were observed continuously over the calving period and delivery type
      classified as being either eutocic or dystocic. The occurrence of dystocia was
      14.1%. Increased calf birth weight increased the odds of occurrence of dystocia
      (odds ratio (OR)=1.40; 95% confidence interval (95% CI) 1.12-1.76; P<0.01). High
      diets in the second trimester were associated with heavier calves at birth
      (P=0.01). The mean pelvic area of eutocic heifers on -72 d, tended to be greater
      compared to that of dystocic heifers (P=0.08) such that a 1-cm(2) difference in
      pelvic area tended to decrease the risk of dystocia (OR=0.97; 95% CI 0.93-1.01;
      P=0.09). Longer gestation length was associated with an increased risk of
      dystocia (P=0.03). ES (P=0.04) and bPL (P=0.09) at calving were positively
      associated with the risk of dystocia. In conclusion, the current study
      demonstrates (a) that pelvic area measurement at selection in 3-year-old Bos
      indicusxBos taurus heifers may be useful for identifying heifers at an increased
      risk of dystocia and (b) increased ES and bPL concentrations at calving are
      associated with increased risk of dystocia. Pelvic area measurements obtained
      prior to conception remain valid in their assessment of the relationship between
      pelvic area and likelihood of dystocia occurring in the event of changing
      maternal nutrient intake during gestation. This is an important finding given
      maternal diets high in protein and energy during the second trimester of
      gestation increased calf birth weight and calf birth weight was associated with
      an increase in the occurrence of dystocia in heifers calving as 3-year olds.

PMID- 19762179
TI  - Circulating estradiol and tumor phenotype in postmenopausal breast cancer
      patients.

PMID- 19762180
TI  - Calcitonin gene-related peptide, adrenomedullin and flushing.
AB  - Administration of calcitonin gene-related peptide (CGRP) or adrenomedullin (AM)
      can cause facial flushing, suggesting that the peptides may be important in hot
      flushes experienced particularly by post-menopausal women. Five studies have
      measured plasma CGRP concentrations in post-menopausal women who suffer from
      flushes; all demonstrated elevations of between 170% and 320% over control. Three
      of the studies showed a temporal relationship between flushes and CGRP elevation.
      A further study has shown that CGRP is elevated in the urine of women who suffer
      from flushes. Only a single study has investigated flushes in pre-menopausal
      women; no elevation of CGRP was observed. Flushes are also experienced by men
      undergoing androgen deprivation therapy. Whilst one study failed to find any
      increase in CGRP in the urine of these individuals, a small study has identified
      an increase in plasma CGRP. No studies have investigated plasma AM or the related
      peptide, intermedin/AM2. Overall, there is good evidence to show that flushes in
      post-menopausal women are accompanied by an increase in CGRP. CGRP could act
      centrally on the thermoregulatory centre of the hypothalamus as well as
      peripherally to cause vasodilation and sweating. However, it remains to be
      demonstrated that the elevated CGRP causes flushes. Recently developed CGRP
      antagonists provide an opportunity to test this hypothesis. If they are
      successful, they may represent a useful alternative to oestrogen replacement
      therapy.

PMID- 19762181
TI  - More hypothyroidism and less hyperthyroidism with sufficient iodine nutrition
      compared to mild iodine deficiency--a comparative population-based study of older
      people.
AB  - OBJECTIVE: To assess the occurrence of thyroid disorders and autoimmunity in a
      geriatric population with long-standing recommended iodine intake of natural
      origin compared to mild iodine deficiency. DESIGN AND SETTING: Cross-sectional,
      comparative, population-based study in two areas with different iodine intakes
      due to different tap water iodine contents. PARTICIPANTS: Residents of Randers
      (n=212) or Skagen (n=218), Denmark, aged 75-80 years. MEASURES: Blood samples
      were collected for measuring thyrotropin (TSH), triiodothyronine, thyroxine,
      thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TGAb), thyroglobulin
      (TG); iodine excretion estimated from iodine and creatinine measured in spot
      urine samples; questionnaire on history of thyroid disease, medication and
      vitamin use; clinical examination of the neck. RESULTS: Median urinary iodine
      excretion was 50 microg/24h in Randers and 177 microg/24h in Skagen (p<0.001). A
      history of thyroid disease was reported by 40 (9.3%) dominated by goitre (n=22)
      in Randers and hypothyroidism and Graves Disease (n=15) in Skagen (p<0.001). We
      found visible goitre in 26% of Randers dwellers and none in Skagen (p<0.001).
      Hyperthyroidism with TSH below the reference range was present in 26% of Randers
      and 6% of Skagen dwellers while 6% and 13%, respectively, were hypothyroid with
      TSH above the reference range (p<0.001). More Randers than Skagen participants
      harboured a thyroid antibody (42% vs. 32%, p=0.006). CONCLUSIONS: Recommended
      iodine intake associated with more hypothyroidism, less hyperthyroidism and
      goiters, low TGAb prevalence and lower TG level in serum than did iodine
      deficiency. TPOAb was similar in the iodine replete and deficient geriatric
      populations.

PMID- 19762183
TI  - [Nonsurgical therapy of hemorrhoids].
AB  - Hemorrhoids are a clinical and anatomical subject that has not been completely
      investigated. A link between the anatomy and the symptoms has still not been
      established. For this reason, it is difficult to class the different treatments.
      Non-surgical treatment is intended not to remove but to reposition and hold the
      hemorrhoids in an anatomically correct position and the reduce the vascularity.
      Different techniques have been studies but not all of them have been approved.
      For the moment, the recognised techniques include: infrared therapy,
      sclerotherapy, rubber band ligation. Cryotherapy has not been studied in
      controlled studies. One hopes that new techniques such as Doppler-guided artery
      ligation will soon be tested and validated.

PMID- 19762184
TI  - [Chromoendoscopy in inflammatory bowel disease].
AB  - The risk of colorectal cancer in case of IBD-related pancolitis reaches 2% after
      10 years follow-up, 8% after 20 years up to 18% at 30 years, and was probably
      over-estimated in the first series. Chromoendoscopy appears to be helpful in the
      surveillance of IBD, and moreover recommended, using carmine indigo or methylene
      blue with a well-standardized procedure. Its place regarding other techniques
      like virtual coloration has to be clarified with randomized studies. The
      chromoendoscopy allows the operator to perform targeted biopsies, which appear to
      be more efficient for the detection of dysplasia than systematic biopsies
      performed every 10 cm. Nevertheless, it is too soon to remove systematic biopsies
      from scientific recommendations.

PMID- 19762185
TI  - [A case of autoimmune hepatitis].
AB  - Autoimmune hepatitis (AIH) is a disorder of unknown aetiology that occurs in
      children and adults of all ages with a female predominance. The spectrum of
      presentation is wide, ranging from no symptoms to acute liver failure. The
      diagnosis is based on high level or serum gammaglobulins, characteristic
      circulating autoantibodies and histologic abnormalities (necrosis and
      inflammation) in the absence of other causes. AIH is classified on the basis of
      the autoantibody pattern: type 1 (antinuclear and/or smooth muscle antibodies) is
      the classic form whereas type 2 (liver-kidney microsome 1 antibody) is much less
      common and occurs mainly in childhood. Mixed forms of AIH that share features
      with other putative autoimmune liver diseases, primary biliary cirrhosis and
      primary sclerosing cholangitis, have been described. Because of therapeutic
      issues, it is important to distinguish AIH from other forms of hepatitis and the
      use of diagnostic scoring systems may be helpful. Treatment basis of AIH have not
      changed for the last 30 years. Initial treatment consists of corticosteroids
      associated with azathioprine. Budesonide may be at least as effective as systemic
      corticosteroids and reduces the frequency of side effects in non-cirrhotic
      patients. Long-term treatment consists of azathioprine. This treatment is rapidly
      effective but usually only suspensive since relapse after treatment withdrawal is
      the rule (80 % of cases). The probability of relapse is lower in case of complete
      biochemical response defined by normalization of transaminases, gamma-globulins
      and IgG and in case of histological response defined by the lack of interface
      hepatitis. The frequency of side effects justifies an attempt of drug
      discontinuation provided that criteria of clinical, biochemical and histological
      remission are achieved after at least 2 years of treatment.

PMID- 19762186
TI  - Reactive nodular fibrous pseudotumor: a first report of gastric localization and
      clinicopathologic review.
AB  - Reactive nodular fibrous pseudotumor (RNFP) of the gastrointestinal tract is a
      distinct benign lesion, which could originate from a reactive proliferation of
      multipotential subserosal cells. This is the first case to be reported in the
      stomach. It was fortuitously discovered in a 60-year-old man with history of
      bulbar ulcer and gastritis. Gross examination revealed three lesions in the
      gastric wall and an adjacent lesion in the lesser omentum. Histologically,
      lesions were composed of a proliferation of spindle and stellate cells in a dense
      collagenic hyalinized background containing a mononuclear cell inflammatory
      infiltrate with numerous lymphoid aggregates and plasma cells with perivascular
      disposition. Immunohistochemistry showed staining for cytokeratins (AE1/AE3),
      vimentin and smooth muscle actin, without staining for the neurofilament and S100
      proteins, synaptophysin, calretinin, CD117 (c-kit), CD34, desmin, caldesmon or
      anaplastic lymphoma kinase (ALK-1). Complete excision was performed, and no
      evidence of disease was found 4 months later. After analysing clinical,
      morphological and immunohistochemical features of this entity, the main
      differential diagnoses will be discussed, including calcifying fibrous
      pseudotumor, which shares morphological characteristics with RNFP, but which
      immunohistochemistry and the ultrastructural study suggest that it may be a
      result of another reactive process.

PMID- 19762187
TI  - [A 23-year-old asymptomatic HBsAg positive woman].
AB  - This paper discusses the case of a young 23-year-old asymptomatic HBsAg woman,
      diagnosed in the immune-tolerance phase of HBV infection. The monitoring shows
      the loss of tolerance and eventually the transition to the inactive carrier
      state. Management strategies are discussed for each phase according to the recent
      EASL guidelines.

PMID- 19762188
TI  - [How to investigate and diagnose autochthonous hepatitis E?].
AB  - In developed countries, HEV infection was still recently considered as rare, and
      as an imported disease from endemic areas by travellers. Hepatitis E virus is now
      recognized mainly as an autochthonous disease in these countries. Although the
      source and the route of contamination remain uncertain, several cases of food
      borne (zoonotic transmission) and blood-borne transmission have been recently
      reported. The mortality rates in industrialized countries seems to be higher than
      in endemic areas, since the infection occurs more frequently in elderly people
      with underlying chronic liver disease (mortality rate approaching 70% in this
      subgroup of patients). By contrast, whereas mortality rate rises by 20% during
      pregnancy in developing countries, no death in pregnant woman from developed
      countries secondary to an autochthonous case has been reported so far. Lastly,
      HEV infection may be a cause of chronic hepatitis in immunocompromised patients
      (mostly in solid organ-transplant recipients) which can evolve to cirrhosis.

PMID- 19762189
TI  - [Low-volume PEG solution-associated colitis].

PMID- 19762190
TI  - Endoscopic submucosal dissection for colorectal tumors.
AB  - BACKGROUND: Endoscopic submucosal dissection (ESD) is a state-of-the-art method
      that enables resection of larger tumors than those resectable by conventional
      endoscopic mucosal resection (EMR). However, the individual role of each method
      in the treatment of colorectal tumors remains undetermined. OBJECTIVE AND
      METHODS: To consider the respective indications of ESD and EMR for colorectal
      tumors, we analyzed the results of the two treatments retrospectively. RESULTS:
      Tumors treated by ESD (44 tumors) were significantly larger, more often located
      in the rectum and more often coexistent with cancer than those treated by EMR
      (512 tumors). EMR was used in the majority of adenomas, and showed high rates of
      both one-piece resection (OPR) and complete resection (CR) for adenomas less than
      20 mm. However, for adenomas and cancers greater or equal to 20 mm, the CR rate
      for EMR was significantly lower than that for ESD because of the incidence of OPR
      with a positive lateral margin (16% vs 0% with ESD vs EMR). Histopathology
      (cancer), size (> or =20 mm) and macroscopic type (laterally spreading tumors)
      were shown to be significant risk factors for that incidence. For tumors with
      these factors, ESD showed a higher CR rate than did EMR. However, ESD required
      longer operating times and tended to have a higher rate of perforation compared
      with EMR. ESD was aborted halfway in seven cases due to technical difficulties
      and perforation. CONCLUSION: ESD and EMR have different characteristics as
      treatment for colorectal tumors. Careful evaluation of the lesion and of the
      balance between benefits and risks are mandatory before selecting either of these
      treatments for colorectal tumors.

PMID- 19762191
TI  - Hepatic iron overload and risk of hepatocellular carcinoma in cirrhosis.
AB  - Iron accumulation in the liver is considered to be a co-factor for progression of
      liver disease. Iron overload can enhance the effects of oxidative stress and
      influence the natural history of patients with cirrhosis, exposing them to a
      higher risk of hepatocellular carcinoma. The results of clinical studies designed
      to assess the impact of liver iron content on the risk of tumor development have
      remained controversial for some time. It is known that common factors can affect
      both liver iron overload and the risk of cancer, necessitating multivariate
      analyses of these features in large cohorts of cirrhotic patients. Furthermore,
      the causes and consequences of hepatic iron overload appear to depend on the
      cause of the underlying liver disease. Thus, the only solid evidence of a
      relationship between liver iron overload and event occurrence has come from
      longitudinal studies conducted in homogeneous cohorts of patients with cirrhosis.
      So far, the available data suggest that iron accumulation in the liver is an
      independent risk factor for hepatocellular carcinoma in patients with alcoholic
      cirrhosis and/or nonalcoholic hepatosteatosis, but not in those with viral
      hepatitis C cirrhosis.

PMID- 19762192
TI  - [Sentinel lymph node biopsy in anal cancer].

PMID- 19762193
TI  - Stapled haemorrhoidopexy for the treatment of haemorrhoids.

PMID- 19762194
TI  - Disseminated Rhodococcus equi infection in a kidney transplant patient without
      initial pulmonary involvement.
AB  - Rhodococcus equi is increasingly recognized as an opportunistic pathogen in solid
      organ transplant recipients. Primary pulmonary involvement is the most common
      finding. We report a case of a 42-year-old female kidney transplant recipient who
      developed multiple disseminated abscesses caused by R. equi while on adequate
      antimicrobial therapy. The patient presented with subcutaneous abscesses in the
      hip region and mamma and had 2 intracerebral abscesses. There were no clinical
      and radiologic signs of pulmonary involvement in contrast to most clinical cases
      described in the literature. R. equi was cultured from all abscesses. The patient
      died of progressive neurologic complications. Post mortem examination confirmed
      infection with R. equi and showed microscopic evidence of necrotizing pneumonia.
      This report shows that R. equi should be considered as a cause of infection in
      solid organ transplant recipients even without initial clinical and radiologic
      signs of pulmonary involvement. Despite adequate therapy, the outcome can be
      fatal.

PMID- 19762195
TI  - Concurrent measurement of adenosine deaminase and dipeptidyl peptidase IV
      activity in the diagnosis of tuberculous pleural effusion.
AB  - Measurement of pleural fluid adenosine deaminase (ADA) levels aids diagnosing
      tuberculous pleural effusion (TPE). Dipeptidyl peptidase IV (DPP) enzyme is
      closely related to ADA. Our aim was to determine the value of concurrent
      measurement of these T-cell-associated enzymes, ADA and DPP levels in the
      diagnosis of TPE. Patients with pleural effusion were grouped as TPE,
      parapneumonic, malignant, congestive heart failure related, and miscellaneous
      pleural effusions. Pleural and serum ADA and DPP levels were measured. Pleural
      and serum levels of ADA and pleural DPP were higher in TPE group than the rest.
      In 7 patients, pleural biopsy revealed granulomatous pleuritis. All of these
      patients had TPE and had elevated serum and pleural ADA levels. Serum and pleural
      ADA or DPP levels and pleural ADA and DPP levels correlated with each other.
      Selecting cutoff values of 40 and 27 IU/L for pleural ADA and DPP, respectively,
      the sensitivity of concurrent measurement of both enzymes was 77%, specificity
      94%, and diagnostic efficiency 91%. ADA and DPP play an important role in
      tuberculous immunopathogenesis. The utility of DPP in the diagnosis of TPE has
      never been determined before. Concurrent measurement of ADA-DPP can aid in
      diagnosing TPE with higher specificity, sensitivity, and efficiency.

PMID- 19762196
TI  - Evidence for daptomycin Etest lot-related MIC elevations for Staphylococcus
      aureus.
AB  - MIC testing was performed simultaneously by Etest and broth microdilution (BMD)
      on 587 Staphylococcus aureus isolates submitted by local laboratories to a
      reference laboratory for confirmatory testing (May 2005 to July 2008). Testing
      bias was assessed for Etest to BMD MIC ratios. Categoric and essential agreement,
      very major (BMD nonsusceptible, Etest susceptible), and major (BMD susceptible,
      Etest nonsusceptible) errors were evaluated. Agar and broth calcium
      concentrations were consistent with current Clinical and Laboratory Standards
      Institute and manufacturer recommendations. There was a consistent bias for
      higher Etest MIC values compared with BMD. Ratios ranged from 0.25 to 4 (average
      1.3), with substantial variability noted among the 8 different Etest lots tested.
      Overall, 6% of all ratios were >2.0. Categoric agreement and essential agreement
      among the 8 Etest lots ranged from 73% to 96% and 74% to 100%, respectively; very
      major errors ranged from 3% to 9%, and major errors ranged from 6% to 35%.
      However, most of the discrepancies were limited to 3 Etest lots.

PMID- 19762197
TI  - The information and support needs of patients diagnosed with High Grade Glioma.
AB  - OBJECTIVE: To understand patients' experiences of High Grade Glioma and identify
      and describe information and support needs along the disease trajectory. METHODS:
      Semi-structured interviews were conducted with 19 patients. Data was analysed
      using grounded theory and the constant comparative method. RESULTS: Four major
      themes were identified: (1) feelings of uncertainty around prognosis and quality
      of life; (2) the need for individualised information; (3) dependence on carers
      due to cognitive deficits, loss of balance and inability to drive; and (4)
      communication with health professionals around prognostic uncertainty and disease
      progression with communication barriers due to complex language deficits.
      CONCLUSION: Previous studies in HGG pre-date the current combined modality
      standard of care, or examined a mixed population. This study has found that
      patients with HGG have needs that differ from other patients with terminal
      malignancy and that these needs change over time with disease progression.
      PRACTICE IMPLICATIONS: This study has identified that patients with brain tumours
      may have unique needs. Health professionals need to clarify patients' information
      and support needs and be aware that these change over and within time.

PMID- 19762198
TI  - Assisting the diagnosis of Graves' hyperthyroidism with Bayesian-type and SOM
      type neural networks by making use of a set of three routine tests and their
      correlation with free T4.
AB  - In our previous paper, we proposed a novel screening method that assists the
      diagnosis of Graves' hyperthyroidism via two types of neural networks by making
      use of routine test data. This method can be applied by non-specialists during
      physical check-ups at a low cost and is expected to lead to rapid referrals for
      examination and treatment by thyroid specialists, that is, to improve patients'
      QOL. In this report, the amount of female sample data was increased and routine
      test data (14 parameters) from 120 subjects with a known diagnosis (35 patients
      with Graves' hyperthyroidism and 85 healthy volunteers) were adopted as training
      data, before 171 individuals who had also undergone the same routine tests at the
      Tohoku University Hospital were screened by the network for Graves'
      hyperthyroidism. The present re-examination of the screening method showed its
      high screening ability with the set of parameters used (low serum creatinine was
      added to the established measures of elevated alkaline phosphatase and low total
      cholesterol that appear in the Graves' hyperthyroidism guidelines) and robustness
      due to the increase of the training sample data. It was also found that there is
      a strong correlation between the three parameters and serum free thyroxine (FT4)
      in Graves' hyperthyroidism, which supports the usefulness of our screening
      method.

PMID- 19762199
TI  - Anticancer activity of fungal taxol derived from Botryodiplodia theobromae Pat.,
      an endophytic fungus, against 7, 12 dimethyl benz(a)anthracene (DMBA)-induced
      mammary gland carcinogenesis in Sprague Dawley rats.
AB  - Breast cancer is the second most prevalent cancer worldwide and their incidence
      increases gradually. Taxol (paclitaxel), a potent anticancer drug, is naturally
      isolated from the bark of the Pacific yew. Taxol is widely used in the treatment
      of ovarian, lung and breast cancer. The increased demand for taxol, coupled with
      its limited availability from the protected Pacific yew, has had researchers
      scrambling for alternate sources. The purpose of the present study is to
      investigate chemopreventive effect of fungal taxol derived from a novel
      endophytic fungus Botryodiplodia theobromae Pat., isolated from a medicinal plant
      Morinda citrifolia Linn. The fungal taxol is found to be active against the 7, 12
      dimethyl benz(a)anthracene (DMBA)-induced mammary gland carcinogenesis in Sprague
      dawley rats. The enzymic and non-enzymic antioxidants i.e. superoxide dismutase
      (SOD), catalase (CAT), glutatione peroxidase (GPx), glutatione-S-transferase
      (GST), reduced glutathione (GSH), vitamin C and vitamin E were evaluated in
      control and experimental groups. Lipid peroxides levels (LPO) were also tested.
      Histological analysis of breast tissue was analyzed by haematoxylin and eosin
      staining to assess the cytoprotective role of fungal taxol active against breast
      cancer. Immunohistochemical analyses were also performed to evaluate the effect
      of fungal taxol on the inflammatory marker such as Cyclooxygenase-2 (COX-2) in
      control and experimental groups. The results showed that the fungal taxol
      significantly suppresses the DMBA-induced breast cancer in Sprague dawley rats.

PMID- 19762200
TI  - [Searching French institutional health information sources: catalogue and index
      of French-language medical sites (CISMeF)].
AB  - The Catalogue and index of French-language medical sites (CISMeF) is a medical
      portal that provides users with results as pertinent as possible according to
      their requirements, expectations, and context of use. Indexing and single-term
      research are based on theMedical subject headings(MeSH) thesaurus. The
      integration of new medical terminology for indexing the catalogue's resources is
      intended to minimize false-negatives during searches and to contextualize the
      users' needs. The creation of a drug information portal makes more targeted
      research possible, with numerous entries according to user (physicians,
      pharmacists, chemists, and pharmacologists). For simplicity's sake, the
      catalogue's index of resources by different nomenclatures is not entirely
      displayed. The choice of display is left to the user, with MeSH only as the
      default. These multi-nomenclature tools should be applicable as well to
      electronic patient records. In this case, the objective is to improve patient
      care by better searches and identification of the information required during
      consultations and hospitalization.

PMID- 19762201
TI  - [Impact of non-cardiac surgery on the course of ischemic heart disease].
AB  - The number of patients with cardiac disease undergoing non-cardiac surgery is
      increasing. Preoperative clinical risk stratification is based mainly on clinical
      evaluation. For patients with risk factors, pharmacologic therapy appears to be
      more effective than coronary revascularization. Adverse perioperative cardiac
      events, demonstrated by perioperative elevation of cardiac troponin I above the
      99(th)percentile, predict postoperative and intermediate-term mortality. Beta
      blockers decrease the risk of major perioperative cardiac events. Their benefits
      for intermediate and long-term cardiac morbidity remain to be demonstrated.

PMID- 19762202
TI  - [Gamma-hydroxybutyric acid (GHB): more than a date rape drug, a potentially
      addictive drug].
AB  - According to available information, GHB and its precursors--gamma-butyrolactone
      (GBL) and 1,4-butanediol (1,4BD)--are used especially in a nightlife scene
      characterized by the search for amplified sensations through the combination of
      electronic music, marathon dancing, and substance abuse. Evidence indicates that
      GHB/GHL is used particularly in some subpopulations and in places, such as in gay
      nightclubs. Commonly known as Gorliquid ecstasy, it was misused in the 1980s for
      its bodybuilding effects and in the 1990s as a recreational drug at music venues.
      In the same period, media coverage of the use of GHB in sexual assault (often
      referred to as date rape) brought the drug into the spotlight. GHB/GHL addiction
      is a recognized clinical entity evidenced by severe withdrawal symptoms when the
      drug is abruptly discontinued after regular or chronic use. There is evidence
      that negative health and social consequences may occur in recreational and
      chronic users. Nonfatal overdoses and deaths related to GHB have been reported.
      These undesirable effects and especially the deaths appear to have prompted
      campaigns to limit the use of GHB. Clinicians must also be aware of GBL, which is
      being sold and used as a substitute for GHB.

PMID- 19762203
TI  - [Short- and long-term risks and consequences of anesthesia].

PMID- 19762204
TI  - RE: "Posterior approach with posterior soft tissue repair in revision total hip
      arthroplasty" by Suh et al Vol. 23, No. 8, 2008, p. 1197-1203.

PMID- 19762205
TI  - A distal fluted, proximal modular femoral prosthesis in revision hip
      arthroplasty.
AB  - Most reports on the use of modular femoral stems during revision surgery have
      involved short follow-up periods. The authors evaluated the clinical and
      radiographic performance of 59 patients fitted with a distal fix modular stem.
      The average follow-up period was 8.2 years. Average Harris hip score was improved
      from 47 to 87.6. Of 19 patients with trochanteric osteotomy, 4 had a displaced
      greater trochanter. Re-revision was performed in 5 patients, and 3 of these were
      for subsidence (of these 3, subsidence was associated with dissociation of the
      coupling part in 1 and with osteotomy nonunion in other 2 [proximal component
      only]). Modular distally fixed femoral stems were found to offer intraoperative
      flexibility, but to suffer from subsidence and intraoperative greater trochanter
      and metaphyseal femoral fractures.

PMID- 19762206
TI  - Early outcomes from a randomized, controlled trial of supervised exercise,
      angioplasty, and combined therapy in intermittent claudication.
AB  - BACKGROUND: To compare angioplasty (PTA), supervised exercise (SEP) and PTA + SEP
      in the treatment of intermittent claudication (IC) due to femoropopliteal
      disease. METHODS: Over a 6-year period, 178 patients (108 men; median age, 70
      years) with femoropopliteal lesions suitable for angioplasty were randomized to
      PTA, SEP, or PTA + SEP. Patients were assessed prior to and at 1 and 3 months
      post treatment. ISCVS outcome criteria (ankle pressures, treadmill walking
      distances) and quality of life (QoL) questionnaires (SF-36 and VascuQoL) were
      analyzed. RESULTS: All groups were well matched at baseline. Twenty-one patients
      withdrew. Results are as follows: Intragroup analysis: All groups demonstrated
      significant clinical and QoL improvements (Friedman test, p < 0.05). SEP (60
      patients, 8 withdrew)-62.7% of patients (n = 32) improved following treatment [20
      mild, 9 moderate, 3 marked], 27.4% (n = 14) demonstrated no improvement, and 9.8%
      (n = 5) deteriorated. PTA (60 patients, 3 withdrew)-66.6% patients (n = 38)
      improved following treatment [19 mild, 10 moderate, 9 marked], 22.8% (n = 13)
      demonstrated no improvement, and 10.5% (n = 6) deteriorated. PTA + SEP (58
      patients, 10 withdrew)-81.6% of patients (n = 40) improved following treatment
      [10 mild, 17 moderate, 3 marked], 14.2% (n = 7) demonstrated no improvement, and
      4.0% (n = 2) deteriorated. Intergroup analysis: PTA + SEP produce a much greater
      improvement in clinical outcome measures than PTA or SEP alone, but there was no
      significant QoL advantage (Kruskal-Wallis test, p > 0.05). CONCLUSION: SEP should
      be the primary treatment for the patients with claudication and PTA should be
      supplemented by an SEP.

PMID- 19762207
TI  - The management of large bilateral internal iliac artery aneurysms using the T
      Stat Colon Oximeter.
AB  - Internal iliac artery (IIA) aneurysms are rare and the repair of these aneurysms
      is associated with high risk of morbidity and mortality. Bilateral IIA aneurysms
      add an increased concern for ischemic complications. A case is presented where
      the use of a Food and Drug Administration-approved device, the T-Stat Colon
      Oximeter, allowed additional information for the safe and successful hybrid
      exclusion of bilateral large IIA aneurysms. A staged approach with the use of
      Amplatzer plugs, Powerlink device, Zenith iliac plug, and a femoral-femoral
      bypass allowed successful exclusion of the IIA aneurysms. The immediate and 18
      month follow-up of the IIA aneurysms are reported.

PMID- 19762208
TI  - Improving BCI performance by task-related trial pruning.
AB  - Noise in electroencephalography data (EEG) is an ubiquitous problem that limits
      the performance of brain computer interfaces (BCI). While typical EEG artifacts
      are usually removed by trial rejection or by filtering, noise induced in the data
      by the subject's failure to produce the required mental state is very harmful.
      Such "noise" effects are rather common, especially for naive subjects in their
      training phase and, thus, standard artifact removal methods would inevitably
      fail. In this paper, we present a novel method which aims to detect such defected
      trials taking into account the intended task by use of Relevant Dimensionality
      Estimation (RDE), a new machine learning method for denoising in feature space.
      In this manner, our method effectively "cleans" the training data and thus allows
      better BCI classification. Preliminary results conducted on a data set of 43
      naive subjects show a significant improvement for 74% of the subjects.

PMID- 19762209
TI  - Intermittent, noncyclic dysfunction of a mechanical aortic prosthesis by pannus
      formation.
AB  - Mechanical aortic prosthesis dysfunction can result from thrombosis or pannus
      formation. Pannus formation usually restricts systolic excursion of the occluding
      disk, resulting in progressive stenosis of the aortic prosthesis. Intermittent
      dysfunction of a mechanical aortic prosthesis is usually ascribed to thrombus
      formation. We describe an unusual case of intermittent, noncyclic dysfunction of
      a mechanical aortic prosthesis due to pannus formation in the absence of systolic
      restriction of disk excursion that presented with intermittent massive aortic
      regurgitation, severe ischemia, and shock. Pannus formation should be considered
      as a potential cause of acute intermittent severe aortic regurgitation in a
      patient with a mechanical aortic prosthesis.

PMID- 19762210
TI  - When should an interim analysis be unblinded to the data monitoring committee?

PMID- 19762211
TI  - A probiotics trial on trial: the problem of timely detection of adverse advents
      in therapeutic trials.

PMID- 19762212
TI  - Methods to calculate relative risks, risk differences, and numbers needed to
      treat from logistic regression.

PMID- 19762213
TI  - Comparison of two self-rating instruments for medication adherence assessment in
      hypertension revealed insufficient psychometric properties.
AB  - OBJECTIVE: In cases of insufficiently controlled blood pressure, it is important
      for practitioners to distinguish between "nonadherence" and "nonresponse" to
      antihypertensive drug treatment. A reliable and valid adherence measurement based
      on the patient's self-report may be helpful in daily practice. STUDY DESIGN AND
      SETTING: In a primary care sample with 353 hypertensive patients, we applied two
      self-rating instruments to assess medication adherence (the "Hill-Bone Compliance
      to High Blood Pressure Therapy Scale" and Morisky's "Self-Reported Measure of
      Medication Adherence") and compared their psychometric properties. RESULTS: Both
      scales showed low acceptability and insufficiency to moderate internal
      consistency (Cronbach's alpha=0.25 and 0.73, respectively). Their convergent
      validity as indexed by kappa=0.39 could be judged as "fair" at best. Testing the
      power to predict blood pressure >140/90mmHg, both scales showed an accuracy of
      57% and 62%, respectively. The positive likelihood, that is, the increase in
      likelihood of high blood pressure in cases of nonadherence was 1.00 and 1.32,
      respectively. CONCLUSION: The use of both scales cannot be recommended. They
      showed considerable floor effects, and their ability to identify medication
      adherence was inconsistent for nearly every third patient. The power of both
      scales to predict uncontrolled blood pressure was essentially a chance. The
      underlying conceptual framework of medication adherence therefore needs to be
      rethought.

PMID- 19762214
TI  - Fuzzy anatomical connectedness of the brain using single and multiple fibre
      orientations estimated from diffusion MRI.
AB  - A new fuzzy algorithm for assessing white matter connectivity in the brain using
      diffusion-weighted magnetic resonance images is presented. The proposed method
      considers anatomical paths as chains of linked neighbouring voxels. Links between
      neighbours are assigned weights using the respective fibre orientation estimates.
      By checking all possible paths between any two voxels, a connectedness value is
      assigned, representative of the weakest link of the strongest path connecting the
      voxel pair. Multiple orientations within a voxel can be incorporated, thus
      allowing the utilization of fibre crossing information, while fibre branching is
      inherently considered. Under the assumption that paths connected strongly to a
      seed will exhibit adequate orientational coherence, fuzzy connectedness values
      offer a relative measure of path feasibility. The algorithm is validated using
      simulations and results are shown on diffusion tensor and Q-ball images.

PMID- 19762215
TI  - Pomegranate juice polyphenols increase recombinant paraoxonase-1 binding to high
      density lipoprotein: studies in vitro and in diabetic patients.
AB  - OBJECTIVE: The high-density lipoprotein (HDL)-associated paraoxonase-1
      (PON1)/free PON1 ratio is lower in diabetic patients in comparison with healthy
      controls. Because diabetes is associated with increased oxidative stress, we
      hypothesized that a labeled recombinant PON1 (rePON1) would detect differences in
      HDL capacity to bind PON1 under specific experimental conditions, such as
      oxidation, addition of polyphenols, or in vivo dosing of diabetic patients with
      polyphenols. METHODS: In the present study we determined labeled rePON1 binding
      to HDL under various oxidative conditions by using polyacrylamide gel
      electrophoresis for the separation of free labeled rePON1 from HDL-bound labeled
      rePON1. RESULTS: The HDL-rePON1/free rePON1 ratio gradually decreased as the
      extent of HDL oxidation increased, and the antioxidants vitamin E or pomegranate
      juice (PJ) inhibited the redistribution of rePON1. PJ or its purified
      polyphenols, punicalagin, gallic acid, or ellagic acid, increased rePON1 binding
      also to non-oxidized HDL. Further, rePON1 associated more efficiently with HDLs
      isolated from diabetic patients after PJ consumption versus HDLs isolated before
      PJ consumption. CONCLUSIONS: We conclude that 1) oxidative stress impairs binding
      of fluorescein isothiocyanate-labeled rePON1 to HDL and 2) PJ polyphenols
      directly increase the HDL-rePON1 association beyond their antioxidative effect.

PMID- 19762216
TI  - Left-sided EEG focus and positive psychiatric family history are independent risk
      factors for affective disorders in temporal lobe epilepsy.
AB  - OBJECTIVE: To identify independent risk factors for affective disorders in
      temporal lobe epilepsy. METHODS: We studied 97 patients with temporal lobe
      epilepsy (TLE) exploring variables like age, gender, family history of epilepsy
      and psychiatric disorders, duration of epilepsy, control of seizures, presence of
      aura and initial precipitant insult, abuse of substances, neuroimaging and EEG
      features. RESULTS: Forty-one patients (42.3% of the total population) had
      affective disorders. A positive family history of psychiatric disorders
      (O.R.=3.8; p=0.003) and interictal EEG epileptiform discharges involving the left
      temporal lobe (O.R.=2.9; p=0.041) were significantly associated with an increased
      risk for an affective disorder. These associations remained significant after
      logistic regression, confirming the independent effects of the risk factors
      observed. Moreover, a binary logistic regression model obtained was able to
      correctly predict presence or absence of a life-time affective disorder in 71.1%
      of patients. CONCLUSION: This study points out that a positive family history of
      psychiatric disorders and interictal EEG epileptiform discharges involving the
      left temporal lobe are isolated risk factors for affective disorders in TLE. Our
      results suggest that biological factors are crucial for affective disorders
      development in TLE. Further studies are necessary to better specify the genetic
      and anatomical substracts involved and how they come together to generate
      affective disorders in those patients.

PMID- 19762218
TI  - Probe chemistry effect on surface properties of asymmetric-phase lipid bilayers.
AB  - Phospholipid bilayers were formed on mica using Langmuir-Blodgett technique and
      liposome fusion, as a model system for biomembranes. Nanometer-scale surface
      physical properties were quantitatively characterized upon the different phases
      of the monolayers with the different surface chemistry. The less hydration/steric
      forces were observed at the liquid-phase of the lipid layer than at the solid
      phase for the OH-modified probe, while the forces with the CH(3)-modified probe
      were independent of the mechanical stability of the layer. The forces appear to
      be related to the surface chemistry of the probe to the layer as well as the
      mechanical stability of the lipid layer, which depends on the phase and the
      asymmetry of the lipid bilayer. After the breakthrough of the lipid bilayer, the
      CH(3)-modified probe adhered more strongly to the lipid bilayers than do the OH
      modified probe. Using results from the JKR theory, it is found that the adhesion
      can be accounted for in both cases by surface energy consideration, not
      mechanical effects.

PMID- 19762219
TI  - Prediction of short survival in patients with brain metastases based on three
      different scores: a role for 'triple-negative' status?
AB  - AIMS: To evaluate models predicting short survival in patients with brain
      metastases treated with whole-brain radiotherapy (WBRT). MATERIALS AND METHODS:
      This was a retrospective analysis of 312 patients. Each patient was assigned to
      three different four-tiered prognostic scores: the Basic Score for Brain
      Metastases (BSBM), the Graded Prognostic Assessment (GPA) and the score developed
      by Rades et al. In addition, a 'triple-negative' cohort was evaluated (all three
      scores predicted unfavourable prognosis, n=30). RESULTS: No statistically
      significant survival differences were found between the most unfavourable BSBM,
      GPA, Rades et al. and 'triple-negative' groups. The BSBM best predicted short
      survival: patients classified in the unfavourable group (Karnofsky performance
      status <80, uncontrolled primary tumour and presence of extracranial metastases)
      had a 12.5% survival at 4 months and a 0% 1-year survival. Patients in this group
      who survived for 4 months or more had simultaneously detected cancer and brain
      metastases, were treatment naive, and received systemic therapy in addition to
      WBRT. Excluding this type of patient from the analysis resulted in survival
      figures that were indistinguishable from those obtained with best supportive care
      without WBRT in other studies. CONCLUSIONS: Although continuous research is
      necessary to identify patients who can be managed safely and palliated without
      WBRT, we feel that a model of the BSBM unfavourable group (Karnofsky performance
      status <80, uncontrolled primary tumour and presence of extracranial metastases)
      and no intent to treat systemically might form a basis for validation in other
      large databases. The triple-negativity criterion was not superior for predicting
      poor prognosis.

PMID- 19762220
TI  - Didecyldimethylammonium chloride induces pulmonary inflammation and fibrosis in
      mice.
AB  - Didecyldimethylammonium chloride (DDAC) is used worldwide as a germicide, in
      antiseptics, and as a wood preservative, and can cause adverse pulmonary disease
      in humans. However, the pulmonary toxicity of DDAC has not yet been thoroughly
      investigated. Mice were intratracheally instilled with DDAC to the lung and the
      bronchoalveolar lavage (BAL) fluid and lung tissues were collected to assess dose
      and time-related pulmonary injury. Exposure to 1500 MUg/kg of DDAC caused severe
      morbidity with pulmonary congestive oedema. When the BAL fluid from survivors was
      examined on day 3 after treatment, exposure to 150 MUg/kg of DDAC caused weakly
      induced inflammation, and exposure to 15MUg/kg did not cause any visible effects.
      Next, we observed pulmonary changes that occurred up to day 20 after 150 MUg/kg
      of DDAC exposure. Pulmonary inflammation peaked on day 7 and was confirmed by
      expression of interleukin-6, monocyte chemotactic protein-1, macrophage
      inflammatory protein (MIP)-1alpha, MIP-1beta, and regulated upon activation,
      normal T-cell expressed and secreted in the BAL fluid; these changes were
      accompanied by altered gene expression of their chemokine (C-C motif) receptor
      (Ccr) 1, Ccr2, Ccr3, and Ccr5. Cytotoxicity evoked by DDAC was related to the
      inflammatory changes and was confirmed by an in vitro study using isolated mouse
      lung fibroblasts. The inflammatory phase was accompanied or followed by pulmonary
      remodeling, i.e., fibrosis, which was evident in the mRNA expression of type I
      procollagen. These results suggest that administering DDAC by intratracheal
      instillation causes pulmonary injury in mice, and occupational exposure to DDAC
      might be a potential hazard to human health.

PMID- 19762221
TI  - Leishmanicidal activity of benzophenones and extracts from Garcinia brasiliensis
      Mart. fruits.
AB  - Infections by protozoans of the genus Leishmania are the major worldwide health
      problem, with high endemicity in developing countries. The drugs of choice for
      the treatment of leishmaniasis are the pentavalent antimonials, which exert renal
      and cardiac toxicity. Thus, there is a strong need for safer and more effective
      treatments against leishmaniasis. The present study was designated to evaluate,
      by a bioguided assay, the leishmanicidal activity of extracts (hexane, ethyl
      acetate and ethanolic) and molecules both obtained by means of extraction from
      pericarps of Garcinia brasiliensis fruits. The hexane extract presented the best
      activity on the extracellular (promastigotes) and intracellular (amastigotes)
      forms of Leishmania (L.) amazonensis, when compared to the other extracts. Based
      on these findings, this extract was fractionated by silica gel column
      chromatography, affording nine fractions then resulting in three purified
      prenylated benzophenones - 7-epi-clusianone (1), garciniaphenone (2) and
      guttiferone-a (3). They showed significant activity on Leishmania (L.)
      amazonensis, and little toxicity for mammalian cells. Structure-activity
      relationships were evaluated showing that the IC(50) value displayed is dependent
      of prenyl groups and phenolic hydroxyls number, and inversely proportional to the
      hydrophobicity. Our results are promising, showing that these compounds are
      biologically active on Leishmania (L.) amazonensis.

PMID- 19762222
TI  - Budesonide/formoterol maintenance and reliever therapy versus conventional best
      practice.
AB  - Budesonide/formoterol maintenance and reliever therapy (Symbicort SMART) reduces
      asthma exacerbations and symptoms versus fixed-dose regimens plus short-acting
      beta(2)-agonists (SABA) in double-blind trials. Information is lacking regarding
      its effectiveness versus conventional best practice (CBP). This pooled analysis
      of six 6-month, randomized, open-label studies examined asthma control and
      exacerbation risk in asthmatics (aged> or =12 years). Patients (N=7855)
      symptomatic on inhaled corticosteroids (ICS) or stable/symptomatic on ICS/long
      acting beta(2)-agonists (LABA) received budesonide/formoterol maintenance and
      reliever therapy (160/4.5microg bid and as needed) or CBP (ICS or ICS/LABA+/
      other agents at an approved dose plus as-needed SABA). Overall asthma control was
      assessed comparing the incidence of exacerbations and levels of asthma control
      using the asthma control questionnaire (ACQ). Budesonide/formoterol maintenance
      and reliever therapy did not significantly reduce time to first severe
      exacerbation (primary variable) versus CBP (P=0.062). However, patients in this
      group experienced 15% fewer exacerbations (0.20 versus 0.24/patient/year;
      P=0.021) and used 27% less ICS (P<0.0001). Odds of remaining well controlled
      (ACQ< or =0.75) over 6 months were higher with budesonide/formoterol maintenance
      and reliever therapy versus CBP (45% versus 41%, odds ratio [OR] 1.29; P<0.01)
      while risk of remaining uncontrolled decreased (25% versus 29%, OR 0.81; P<0.01).
      Budesonide/formoterol maintenance and reliever therapy improves key aspects of
      asthma control versus physicians' choice of CBP.

PMID- 19762223
TI  - Immobilization of acetylcholineesterase-choline oxidase on a gold-platinum
      bimetallic nanoparticles modified glassy carbon electrode for the sensitive
      detection of organophosphate pesticides, carbamates and nerve agents.
AB  - A novel, highly sensitive amperometric biosensor, based on electrodeposition of
      gold-platinum bimetallic nanoparticles onto 3-aminopropyltriethoxy silane
      modified glassy carbon electrode for the detection of paraoxon ethyl, aldicarb,
      and sarin has been developed. The biosensor consists of acetylcholineesterase
      (AChE)/choline oxidase (ChOx) immobilized by cross-linking with glutaraldehyde on
      a modified electrode. The properties of nanoparticles modified electrodes are
      characterized by scanning electron microscopy (SEM), energy dispersive X-ray
      (EDX), cyclic voltammograms (CVs) and electrochemical impedance spectroscopy
      (EIS). The synergistic action of Au and Pt nanoparticles showed excellent
      electrocatalytic activity with low applied potential for the detection of
      hydrogen peroxide (H(2)O(2)). The IC(50) and inhibition rate constant (K(i))
      values were determined for the inhibitors using immobilized enzymes on modified
      electrode and the data were compared by spectrophotometric determination of these
      kinetic parameters using free enzymes in solution. Paraoxon ethyl, sarin, and
      aldicarb could be detected up to 150-200nM, 40-50nM, and 40-60 microM
      respectively at 30-40% inhibition level of AChE enzyme and followed linearity in
      wide range concentration.

PMID- 19762224
TI  - Recent advances in mammalian synthetic biology-design of synthetic transgene
      control networks.
AB  - Capitalizing on an era of functional genomic research, systems biology offers a
      systematic quantitative analysis of existing biological systems thereby providing
      the molecular inventory of biological parts that are currently being used for
      rational synthesis and engineering of complex biological systems with novel and
      potentially useful functions-an emerging discipline known as synthetic biology.
      During the past decade synthetic biology has rapidly developed from simple
      control devices fine-tuning the activity of single genes and proteins to multi
      gene/protein-based transcription and signaling networks providing new insight
      into global control and molecular reaction dynamics, thereby enabling the design
      of novel drug-synthesis pathways as well as genetic devices with unmatched
      biological functions. While pioneering synthetic devices have first been designed
      as test, toy, and teaser systems for use in prokaryotes and lower eukaryotes,
      first examples of a systematic assembly of synthetic gene networks in mammalian
      cells has sketched the full potential of synthetic biology: foster novel
      therapeutic opportunities in gene and cell-based therapies. Here we provide a
      concise overview on the latest advances in mammalian synthetic biology.

PMID- 19762225
TI  - Distinct and dynamic myogenic populations in the vertebrate embryo.
AB  - Myogenic cells in the body of vertebrates derive from the dorsal somite, the
      dermomyotome, where multipotent cells are present. Regulation of cell fate choice
      is discussed, as is that of progenitor cell self-renewal once cells have entered
      the myogenic programme. Ongoing research on the formation of the first skeletal
      muscle, the myotome, is presented with emphasis on mechanisms controlling the
      early segregation of slow and fast muscle lineages that characterizes this
      process in the zebrafish embryo. Further insights into myogenic populations that
      contribute to trunk and limb development at different stages are summarized and
      the distinct regulatory networks that underlie the formation of head muscles are
      discussed.

PMID- 19762226
TI  - Anal cancer: one step forward--two steps sideways!

PMID- 19762227
TI  - Are we there yet? The state of the evidence base for guidelines on breaking bad
      news to cancer patients.
AB  - The way clinicians break bad news to cancer patients has been retrospectively
      associated with poor psychosocial outcomes for patients. Education and practice
      in breaking bad news may be ineffective for improving patients' well-being unless
      it is informed by a sound evidence base. In the health field, research efforts
      are expected to advance evidence over time to inform evidence-based practice. Key
      characteristics of an advancing evidence base are a predominance of new data, and
      rigorous intervention studies which prospectively demonstrate improved outcomes.
      This review aimed to examine the progress of the evidence base in breaking bad
      news to cancer patients. Manual and computer-based searches (Medline and
      PsycINFO) were performed to identify publications on the topic of breaking bad
      news to cancer patients published between January 1995 and March 2009. Relevant
      publications were coded in terms of whether they provided new data, examined
      psychosocial outcomes for patients or tested intervention strategies and whether
      intervention studies met criteria for design rigour. Of the 245 relevant
      publications, 55.5% provided new data and 16.7% were intervention studies. Much
      of the intervention effort was directed towards improving provider skills rather
      than patient outcomes (9.8% of studies). Less than 2% of publications were
      rigorous intervention studies which addressed psychosocial outcomes for patients.
      Rigorous intervention studies which evaluate strategies for improving
      psychosocial outcomes in relation to breaking bad news to cancer patients are
      needed. Current practice and training regarding breaking bad news cannot be
      regarded as evidence-based until further research is completed.

PMID- 19762228
TI  - Contemporary pre-clinical development of anticancer agents--what are the optimal
      preclinical models?
AB  - The successful identification of novel effective anticancer drugs is largely
      dependent on the use of appropriate preclinical experimental models that should
      possibly mimic the complexity of different cancer diseases. The huge number of
      targets suitable for the design of new anticancer drugs is producing hundreds of
      novel molecules that require appropriate experimental models to investigate their
      mode of action and antitumour activity in order to select for clinical
      investigation the ones with higher chances of being clinically effective.
      However, our ability to predict the clinical efficacy of a new compound in the
      clinic based on preclinical data is still limited. This paper overviews the in
      vitro/in vivo preclinical systems that are currently used to test either
      compounds with an unknown mechanism of action or compounds designed to hit cancer
      specific or cancer-related molecular targets. Examples of experimental models
      successfully used to identify novel compounds are provided. Xenografts are still
      the most commonly used in vivo models in drug development due to their high
      degree of reproducibility and because, in some cases, particularly when
      orthotopically transplanted, they maintain several biological properties of the
      human tumours they derive from. Genetic models are very useful for target
      validation, but are often not sufficiently reproducible to be used for drug
      evaluation. The variety of animal models can be effectively used to optimally
      test drugs that presumably act by a defined mode of action, but final success is
      highly dependent on the ability of drug development teams to integrate different
      expertises such as biology, chemistry, pharmacology, toxicology and clinical
      oncology into a clever and well orchestrated plan that keeps in consideration
      both the complexity of cancer diseases, involving alterations of different
      pathways, and the complexity of drugs whose pharmacological properties are
      crucial to obtain the desired effects.

PMID- 19762230
TI  - Deconstructing recalcitrant Miscanthus with alkaline peroxide and electrolyzed
      water.
AB  - A two-stage pretreatment method was proposed and tested for deconstruction of
      recalcitrant Miscanthus. During a 1st pretreatment at 50 degrees C, 1.0-4.0%
      alkaline peroxide solutions were used to partially remove hemicellulose and
      lignin. The remaining solids were subjected to a 2nd pretreatment at 121 degrees
      C with electrolyzed water. Using 15 filter paper units of cellulase per gram
      cellulose, a digestibility of 95% was achieved by the two-stage method, which was
      higher than 81% obtained from a 1% H(2)SO(4) pretreatment (200 degrees C, 8 min).
      A mass balance for the two-stage process showed that 63% hemicellulose and 64%
      lignin were removed from the Miscanthus samples after the 1st pretreatment. The
      Scanning Electron Microscopy images and Fourier Transform Infrared Spectroscopy
      spectra revealed that after the 1st pretreatment, crystalline cellulose fibers
      were partially exposed and the linkages between residual lignin and hemicellulose
      disappeared. After the 2nd pretreatment, cellulose fibers were completely exposed
      even with cracks developed.

PMID- 19762229
TI  - Bio-ethanol from lignocellulose: Status, perspectives and challenges in Malaysia.
AB  - The present study reveals the perspective and challenges of bio-ethanol
      production from lignocellulosic materials in Malaysia. Malaysia has a large
      quantity of lignocellulosic biomass from agriculture waste, forest residues and
      municipal solid waste. In this work, the current status in Malaysia was
      laconically elucidated, including an estimation of biomass availability with a
      total amount of 47,402 dry kton/year. Total capacity and domestic demand of
      second-generation bio-ethanol production in Malaysia were computed to be 26,161
      ton/day and 6677 ton/day, respectively. Hence, it was proven that the country's
      energy demand can be fulfilled with bio-ethanol if lignocellulosic biomass were
      fully converted into bio-ethanol and 19% of the total CO(2) emissions in Malaysia
      could be avoided. Apart from that, an integrated national supply network was
      proposed together with the collection, storage and transportation of raw
      materials and products. Finally, challenges and obstacles in legal context and
      policies implementation were elaborated, as well as infrastructures shortage and
      technology availabilities.

PMID- 19762231
TI  - Life cycle evaluation of emerging lignocellulosic ethanol conversion
      technologies.
AB  - Lignocellulosic ethanol holds promise for addressing climate change and energy
      security issues associated with personal transportation through lowering the fuel
      mixes' carbon intensity and petroleum demand. We compare the technological
      features and life cycle environmental impacts of near- and mid-term ethanol
      bioconversion technologies in the United States. Key uncertainties in the major
      processes: pre-treatment, hydrolysis, and fermentation are evaluated. The
      potential to reduce fossil energy use and greenhouse gas (GHG) emissions varies
      among bioconversion processes, although all options studied are considerably more
      attractive than gasoline. Anticipated future performance is found to be
      considerably more attractive than that published in the literature as being
      achieved to date. Electricity co-product credits are important in characterizing
      the GHG impacts of different ethanol production pathways; however, in the absence
      of near-term liquid transportation fuel alternatives to gasoline, optimizing
      ethanol facilities to produce ethanol (as opposed to co-products) is important
      for reducing the carbon intensity of the road transportation sector and for
      energy security.

PMID- 19762232
TI  - Genetic diversity and characterization of heavy metal-resistant-endophytic
      bacteria from two copper-tolerant plant species on copper mine wasteland.
AB  - The diversity of endophytic bacteria from the copper-tolerant species Elsholtzia
      splendens and Commelina communis was evaluated by using cultivation and
      cultivation-independent techniques. Phylogenetic analysis based on 16S rDNA
      sequences showed that the Cu-resistant isolates belonged to three major
      phylogenetic groups: Firmicutes, Actinobacteria and Proteobacteria. Bacillus and
      Acinetobacter were predominant among the Cu-resistant isolates. Sequence analysis
      from the 16S rDNA clone libraries of the two plant roots revealed sequences of
      Alpha-, Beta-, Gamma-Proteobacteria, Firmicutes,Actinobacteria and Bacteroidetes.
      Gammaproteobacteria was predominant in the two 16S rDNA clone libraries. Thirty
      two endophytic bacteria were isolated and characterized with respect to heavy
      metal resistance and production of plant growth-promoting factors. In experiments
      involving rape plants grown in vermiculite containing 4 mg kg(-1) of Cu,
      inoculation with the isolates was found to increase the dry weights of roots
      (ranging from 132% to 155%) and above-ground tissues (ranging from 71% to 83%)
      compared to the uninoculated control. Increase in above-ground tissue Cu content
      varied from 63% to 125% in inoculated-rape plants cultivated in Cu-contaminated
      substrate compared to the uninoculated control.

PMID- 19762233
TI  - Analysis of the outcome of shredding pretreatment on the anaerobic
      biodegradability of paper and cardboard materials.
AB  - Paper and cardboard stand for the major biodegradable organic fraction of most of
      municipal solid waste (MSW). This article aims at discussing the possible
      positive impact of a thin shredding of this fraction on its biodegradability
      under mesophilic anaerobic conditions, either for landfilling or for digestion in
      industrial reactors. For that purpose, BMP tests were performed on two types of
      paper and cardboard mixtures: one sorted from a complex landfill French MSW
      income, one built from source separated papers and cardboards. For both of these
      substrates, comparison was made between assays on large pieces of waste and
      assays on tiny shredded waste (powder particles of less than 1mm diameter). For
      the second substrate, assays at two different inoculation levels were performed.
      All results are discussed both in terms of maximal methane conversion yields and
      in terms of kinetic rates. The main conclusion is that shredding does not improve
      methane potential of paper and cardboard, neither the biogas production rates.
      This leads the authors to put forward the hypothesis that shredding does not
      significantly either increase enzyme accessibility to cellulose nor favor the
      surface bacterial colonization, although it strongly affects the macrostructure
      of the waste.

PMID- 19762234
TI  - Synthesis, SAR, and X-ray structure of tricyclic compounds as potent FBPase
      inhibitors.
AB  - With the aim of discovering a novel class of fructose-1,6-bisphosphatase (FBPase)
      inhibitors, a series of compounds based on tricyclic scaffolds was synthesized.
      Extensive SAR studies led to the finding of 8l with an IC50 value of 0.013 microM
      against human FBPase. An X-ray crystallographic study revealed that 8l bound at
      AMP binding sites of human liver FBPase with hydrogen bonding interactions
      similar to AMP.

PMID- 19762235
TI  - Design of new antifungal agents: synthesis and evaluation of 1-[(1H-indol-5
      ylmethyl)amino]-2-phenyl-3-(1H-1,2,4-triazol-1-yl)propan-2-ols.
AB  - We previously reported on the design and synthesis of 1-[((hetero)aryl- or
      piperidinylmethyl)amino]-2-phenyl-3-(1H-1,2,4-triazol-1-yl)propan-2-ols showing
      various degrees of antifungal activity against Candida albicans and Aspergillus
      fumigatus strains. Now we have identified a series of 1-[(1H-indol-5
      ylmethyl)amino] derivatives which exhibited potent MICs (<65 ng mL(-1)) against
      C. albicans strain. The synthesis and SAR behind the indole scaffold will be
      discussed.

PMID- 19762236
TI  - The discovery and optimisation of pyrido[2,3-d]pyrimidine-2,4-diamines as potent
      and selective inhibitors of mTOR kinase.
AB  - We describe a novel series of potent inhibitors of the kinase activity of mTOR.
      The compounds display good selectivity relative to other PI3K-related kinase
      family members and, in cellular assays, inhibit both mTORC1 and mTORC2 complexes
      and exhibit good antiproliferative activity.

PMID- 19762237
TI  - First generation 5-vinyl-3-pyridinecarbonitrile PKCtheta inhibitors.
AB  - A series of 5-vinyl-3-pyridinecarbonitriles were synthesized and evaluated as
      PKCtheta inhibitors. The systematic optimization of 4-[(4-methyl-1H-indol-5
      yl)amino]-5-[(E)-2-phenylvinyl]-3-pyridinecarbonitrile 3 resulted in the
      identification of compound 23e as a potent PKCtheta inhibitor with good
      selectivity over PKCdelta.

PMID- 19762238
TI  - Phenylaminopyrimidines as inhibitors of Janus kinases (JAKs).
AB  - A series of phenylaminopyrimidines has been identified as inhibitors of Janus
      kinases (JAKs). Development of this initial series led to the potent JAK2/JAK1
      inhibitor CYT387 (N-(cyanomethyl)-4-[2-[[4-(4-morpholinyl)phenyl]amino]-4
      pyrimidinyl]-benzamide). Details of synthesis and SAR studies of these compounds
      are reported.

PMID- 19762239
TI  - Structure-activity relationship study on alpha1 adrenergic receptor antagonists
      from beer.
AB  - Hordatine A and aperidine have been previously isolated from beer as active
      ingredients, which bind to muscarinic M3 receptor. In addition, these compounds
      have exhibited antagonist activity against the alpha1A adrenoceptor. Although the
      relative structures of these two molecules have previously been determined, the
      absolute stereochemistry was unclear. Hence, to elucidate the absolute
      stereochemistry of natural hordatine A, we synthesized each enantiomer of
      hordatine A and aperidine from optically pure dehydrodi-p-coumaric acid. Several
      additional related compounds were also synthesized for structure-activity
      relationship studies. Chiral column HPLC analysis demonstrated that the absolute
      stereochemistry of natural hordatine A is (2S,3S), while based on the
      isomerization mechanism, the stereochemistry of aperidine is (2R,3S). The alpha1A
      adrenoceptor binding activity of (2R,3R)-hordatine A is the most potent among the
      enantiomeric pairs of hordatines and aperidines. Furthermore, the related,
      synthetic compound, (2R,3R)-methyl benzofurancarboxylate exhibits antagonist
      activity against the alpha1A adrenoceptor at a lower concentration than that of
      hordatine A.

PMID- 19762240
TI  - The discovery and unique pharmacological profile of RO4938581 and RO4882224 as
      potent and selective GABAA alpha5 inverse agonists for the treatment of cognitive
      dysfunction.
AB  - Lead optimisation of the imidazo[1,5-a][1,2,4]-triazolo[1,5-d][1,4]benzodiazepine
      class led to the identification of two clinical leads [RO4882224 (11) and
      RO4938581 (44)] functioning as novel potent and selective GABAA alpha5 inverse
      agonists. The unique pharmacological profiles and optimal pharmacokinetic
      profiles resulted in in vivo activity in selected cognition models.

PMID- 19762241
TI  - Metastatic breast cancer patients: the forgotten heroes!

PMID- 19762242
TI  - Net external energy of the biologic and prosthetic ankle during gait initiation.
AB  - The net external energy of the biologic human ankle joint and of some lower limb
      prosthetic ankle-foot systems was examined during gait initiation. The purpose of
      the study was to better understand the ankle's behavior during the acceleration
      phase of walking for use in the design of improved lower limb prostheses and
      orthoses. Quantitative gait data were collected from 10 able-bodied subjects and
      10 persons with unilateral transtibial amputations during gait initiation. The
      behaviors of the biologic and prosthetic 'ankle' joints were examined by
      analyzing the relationship between sagittal plane ankle angles and moments. Net
      external energy at the ankle was estimated by calculating the area under the
      moment versus angle curves (hysteresis) created during the loading and unloading
      phases. Results indicate that able-bodied persons utilize energy input from the
      trailing ankle after the first step is made in gait initiation, most likely to
      help transition the body into steady-state walking. The passive prosthetic ankle
      foot systems tested were unable to put energy into the system during gait
      initiation.

PMID- 19762243
TI  - Design, synthesis and evaluation of monovalent ligands for the asialoglycoprotein
      receptor (ASGP-R).
AB  - A series of novel aryl-substituted triazolyl D-galactosamine derivatives was
      synthesized as ligands for the carbohydrate recognition domain of the major
      subunit H1 (H1-CRD) of the human asialoglycoprotein receptor (ASGP-R). The
      compounds were biologically evaluated with a newly developed competitive binding
      assay, surface plasmon resonance and by a competitive NMR binding experiment.
      With compound 1b, a new ligand with a twofold improved affinity to the best so
      far known D-GalNAc was identified. This small, drug-like ligand can be used as
      targeting device for drug delivery to hepatocytes.

PMID- 19762244
TI  - Cytosporones, coumarins, and an alkaloid from the endophytic fungus
      Pestalotiopsis sp. isolated from the Chinese mangrove plant Rhizophoramucronata.
AB  - Chemical examination of the endophytic fungus Pestalotiopsis sp., isolated from
      the leaves of the Chinese mangrove Rhizophora mucronata, yielded 11 new compounds
      including cytosporones J-N (1-3, 5-6), five new coumarins pestalasins A-E (8-12),
      and a new alkaloid named pestalotiopsoid A (14), along with the known compounds
      cytosporone C (4), dothiorelone B (7), and 3-hydroxymethyl-6,8-dimethoxycoumarin
      (13). The structures of the new compounds were unambiguously elucidated on the
      basis of extensive spectroscopic data analysis.

PMID- 19762246
TI  - Synthesis of 2- and 17-substituted estrone analogs and their antiproliferative
      structure-activity relationships compared to 2-methoxyestradiol.
AB  - A novel series of 17-modified and 2,17-modified analogs of 2-methoxyestradiol
      (2ME2) were synthesized and characterized. These analogs were designed to retain
      or potentiate the biological activities of 2ME2 and have diminished metabolic
      liability. The analogs were evaluated for antiproliferative activity against MDA
      MB-231 breast tumor cells, antiangiogenic activity in HUVEC, and estrogenic
      activity on MCF-7 cell proliferation. Several analogs were evaluated for
      metabolic stability in human liver microsomes and in vivo in a rat cassette
      dosing model. This study lead to several 17-modified analogs of 2ME2 that have
      similar or improved antiproliferative and antiangiogenic activity, lack
      estrogenic properties and have improved metabolic stability compared to 2ME2.

PMID- 19762245
TI  - The biological activity and metabolic stability of peptidic bifunctional
      compounds that are opioid receptor agonists and neurokinin-1 receptor antagonists
      with a cystine moiety.
AB  - In order to improve metabolic stability, a ring structure with a cystine moiety
      was introduced into TY027 (Tyr-D-Ala-Gly-Phe-Met-Pro-Leu-Trp-NH-[3',5'
      (CF(3))(2)Bzl]), which is a lead compound of our developing bifunctional peptide
      possessing opioid agonist and NK1 antagonist activities. TY038 (Tyr-cyclo[D-Cys
      Gly-Phe-Met-Pro-D-Cys]-Trp-NH-[3',5'-(CF(3))(2)Bzl]) was found as a highly
      selective delta opioid agonist over mu receptor in conventional tissue-based
      assays, together with an effective NK1 antagonist activity and good metabolic
      stability with more than 24h half life in rat plasma.

PMID- 19762247
TI  - A single circularly permuted GFP sensor for inositol-1,3,4,5-tetrakisphosphate
      based on a split PH domain.
AB  - A fluorescent sensor for the detection of inositol-1,3,4,5-tetrakisphosphate,
      Ins(1,3,4,5)P(4), was constructed from a split PH domain and a single circularly
      permuted GFP. A structure-based design was conducted to transduce a ligand
      induced subtle structural perturbation of the split PH domain to an alteration in
      the population of the protonated and the deprotonated states of the GFP
      chromophore. Excitation of each distinct absorption band corresponding to the
      protonated or the deprotonated state of GFP resulted an increase and a decrease,
      respectively, in the intensity of emission spectra upon addition of
      Ins(1,3,4,5)P(4) to the split PH domain-based sensor. The Ins(1,3,4,5)P(4) sensor
      retained the ligand affinity and the selectivity of the parent PH domain, and
      realized the ratiometric fluorescence detection of Ins(1,3,4,5)P(4).

PMID- 19762248
TI  - Study of the IsoAid ADVANTAGE (125)I brachytherapy source dosimetric parameters
      using Monte Carlo simulation.
AB  - Monte Carlo calculations have been performed using the MCNP4C code for an iodine
      seed design. As the ADVANTAGE I-125, Model IAI-125 source is commercially
      available for interstitial brachytherapy treatment, dosimetric characteristics
      (dose rate constant, radial dose function and anisotropy function) of this source
      were theoretically determined following the updated AAPM task group 43 (TG-43U1)
      recommendations. The dose distribution around the seed was calculated with Monte
      Carlo simulation in liquid water. The Monte Carlo calculated dose rate constant
      of this source in water was found to be 0.986cGyh(-1)U(-1), with an approximate
      uncertainty of 0.4%. The obtained result has been compared with the previous
      study. Comparison of the calculated dose rate constant with the value presented
      by Meigooni et al. shows a very good agreement. Also the anisotropy function and
      the radial dose function for this source are graphically compared.

PMID- 19762249
TI  - An automated method for preparation of [(18)F]sodium fluoride for injection, USP
      to address the technetium-99m isotope shortage.
AB  - The worldwide shortage of technetium-99m has created an immediate and urgent need
      for access to [(18)F]sodium fluoride for PET imaging of bone metastasis. In order
      to facilitate global availability of [(18)F]sodium fluoride for diagnostic
      nuclear medicine imaging procedures, a straightforward method for rapid
      production of [(18)F]sodium fluoride for injection, USP, using a modified GE
      Tracerlab FX-FN is presented.

PMID- 19762250
TI  - Awake video-assisted pleural decortication for empyema thoracis.
AB  - OBJECTIVE: To evaluate feasibility, technical features and results of video
      assisted pleural decortication for empyema thoracis performed in awake patients.
      METHODS: This retrospective analysis involved a cohort of 19 patients (median
      age: 58 years) undergoing awake video-assisted thoracoscopic pleural
      decortication under epidural anaesthesia (N=15) or paravertebral blocks (N=4)
      between March 2004 and September 2008. Baseline and perioperative data including
      degree of postoperative lung re-expansion at 48 h, hospital stay, morbidity rate
      and daily fluid loss were recorded. In addition, intra- and perioperative changes
      in main pathophysiological variables PaO(2)/FiO(2) ratio, PaCO(2), mean arterial
      pressure and heart rate were analysed. RESULTS: Origin of the empyema was
      parapneumonic (N=14), post-traumatic (N=3) and cancer related (N=2). All patients
      underwent previous conservative management. The duration of the symptoms averaged
      35 days (quartile range (QR): 28-40). Co-morbidities included chronic obstructive
      pulmonary disease (COPD) (N=4), HIV infection (N=1), diabetes mellitus (N=2) and
      cirrhosis (N=1). Operation was performed videothoracospically in 15 patients
      whereas four patients with major pleural thickening underwent awake lateral
      thoracotomy. Operative time averaged 50 min (QR: 40-70). Perioperative data
      analysis showed no intra-operative deterioration in arterial oxygenation (median
      Delta: 0 mm Hg, QR: -5/+9, P=0.6). Transient permissive hypercapnia (<55 mm Hg)
      developed in three patients with no need of conversion to general anaesthesia.
      Median pain level assessed by a visual analogue score (VAS) 1h postoperatively
      was 4 (QR: 2-5), and it was significantly reduced on postoperative day 1 (median
      3, QR: 2-4, P=0.03). There was neither mortality nor major morbidity.
      Hospitalisation averaged 6 days (QR: 5-7). At postoperative chest X-ray, lung re
      expansion was rated as complete in 16 patients, satisfactory in (>80%) two
      patients and unsatisfactory in a 86-year-old patient with pleural mesothelioma
      who has the chest drain still in place 5 months after surgery. No patient had
      recurrence of the empyema at subsequent follow-ups. CONCLUSIONS: In our study,
      awake video-assisted pleural decortication proved feasible and resulted in
      satisfactory lung re-expansion in 95% of the patients. We hypothesise that
      spontaneous ventilation facilitated both identification of the correct plane and
      dissection, thus resulting in lesser surgical injury on the underlying lung.

PMID- 19762251
TI  - Ross and Yasui operations for complex biventricular repair in infants with
      critical left ventricular outflow tract obstruction.
AB  - OBJECTIVE: To define the outcomes following Ross and Yasui procedures for complex
      biventricular repair of critical left ventricular outflow tract obstruction
      (LVOTO). METHODS: Of 1217 neonates presenting with critical LVOTO enrolled in the
      Congenital Heart Surgeons Society studies (1994-2008), 52 underwent the Ross or
      Yasui procedure and their outcomes were investigated using univariate and
      multivariable parametric models. RESULTS: ROSS (N=39): The Ross procedure (median
      age 87 days) was rarely the primary intervention (5/39, 13%). A significant
      number of cases were performed to treat iatrogenic aortic regurgitation after
      other previous interventions (25/39, 64%). Co-existing functional morphological
      defects were also common: 72% had preoperative evidence of mitral dysfunction,
      moderate-to-severe left ventricular dysfunction or endocardial fibroelastosis.
      Emergency iatrogenic aortic regurgitation (P=0.005) and co-existing abnormalities
      (mitral stenosis, P=0.02; mitral regurgitation, P=0.05; LV dysfunction, P=0.03)
      were strong determinants of death. Severe postoperative ventricular dysfunction
      or need for extracorporeal membrane oxygenation (ECMO) conferred negligible
      survival. Younger age was associated with disproportionately worse late outcome
      (5-year survival 44+/-10% for neonates vs 76+/-8% for age >3 months, P=0.0013).
      However, mitral and left ventricular dysfunction and emergency presentation were
      significantly more common in the younger age groups. Infants less than 3 months
      of age without co-existing abnormalities had acceptable late survival (
      approximately 75+/-20%). YASUI (N=13): Yasui repair (median age 22 days) was
      usually the primary intervention (nine of 13) but occasionally followed Norwood
      palliation (four of 13). None was an emergency. All had a ventricular septal
      defect. Survival was 69+/-13% at 10 years, which is not significantly different
      from other biventricular repair strategies in neonates. Aortic atresia was
      associated with better survival than stenosis (90+/-12% vs 30+/-14% at 3 years,
      P=0.039). None reverted to univentricular physiology later. CONCLUSIONS: Case
      selection is key for complex biventricular repair and the importance of
      appropriate case selection is exaggerated at young ages. All available options
      should be considered before pursuing the Ross operation in the presence of co
      existing functional morphological abnormalities or emergent iatrogenic aortic
      regurgitation. However, both the Ross and Yasui operations in children (including
      neonates and young infants) with favourable functional morphology offer good
      survival, at least matching that of other biventricular repair strategies.

PMID- 19762252
TI  - Blood flow measured by magnetic resonance imaging at rest and exercise after
      surgical bypass of aortic arch obstruction.
AB  - INTRODUCTION: Blood flow distribution after ascending-to-descending aortic bypass
      in complex aortic arch obstruction is poorly described. OBJECTIVE: To study blood
      flow by magnetic resonance (MR) imaging at rest and during exercise in patients
      with aortic arch obstruction and a bypass tube and in healthy controls. MATERIAL
      AND METHODS: Seven patients (median 18 years (range: 14-54 years) and weight 79
      kg (range 51-91 kg)) were studied 25 months (range 6-68 months) following
      surgical insertion of 14- or 16-mm bypass tube from the ascending to the distal
      descending thoracic aorta. Seven sex- and aged-matched normotensive subjects
      served as controls. MR real-time flow was measured in the ascending aorta and the
      proximal descending thoracic aorta in all participants and in the bypass tube in
      patients at rest and during supine leg exercise at 0.5 and 1.0 W kg(-1). RESULTS:
      Ascending aortic flow at rest in patients was 2.9l min(-1)m(-2) (range 2.3-4.4)
      and increased with exercise to 5.3 (range 4.3-7.3) at 1.0 W kg(-1), which was not
      different from controls (3.4 (range 2.4-4.6) and 6.1 (range 5.0-6.9)). The bypass
      tube carried roughly the same flow as the proximal descending aorta at rest (1.5
      (range 0.7-2.0) and 1.0 (range 0.2-2.0), respectively, and flows increased
      similarly during exercise (2.8 (range 1.5-4.0) and 2.0 (range 0.8-4.1),
      respectively at 1.0 W kg(-1)). Flow to the upper body did not differ between
      groups nor changed with supine leg exercise. CONCLUSION: With aortic arch
      obstruction, an ascending-to-descending aortic bypass tube provides normal flow
      to the lower body at rest and during supine leg exercise without evidence of
      steal from the upper body.

PMID- 19762253
TI  - MALDI-TOF-MS analysis of small molecules using modified mesoporous material SBA
      15 as assisted matrix.
AB  - Mesoporous silica, SBA-15 was successfully functionalized with quinoline moiety,
      and was applied as a matrix in the MALDI-TOF-MS analysis of small molecules. The
      modified SBA-15 material [SBA-15-8-(3-(triethoxysilyl)propoxy) quinoline, SBA-15
      8QSi] was obtained by using calcined SBA-15 and 8-hydroxy quinoline. The
      structure of the functionalized mesoporous material was systemically
      characterized by TEM, the N(2) adsorption-desorption isotherm technique and FT-IR
      spectra. Compared with DHB and SBA-15, SBA-15-8QSi demonstrated several
      advantages in the analysis of small molecules with MALDI-TOF-MS, such as less
      background interference ions, high homogeneity, and better reproducibility. Based
      on these results, the various analytical parameters were optimized. The ideal
      operating conditions were (1) methanol used as the dissolving solvent; (2) sample
      first dropping method; (3) a ratio between the analyte and the matrix of 3.5:10.
      Under these optimization conditions, a low detection limit (8 pmol for L-Arginine
      HCl) and high reproducibility (< or = 29%) were obtained. This technique was
      successfully applied to the analysis of various types of small molecules, such as
      saccharides, amino acids, metabolites, and natural honey.

PMID- 19762254
TI  - Is the apical soft tissue margin a better predictor of biochemical recurrence
      than the surgical specimen?
AB  - PURPOSE: To identify predictors of apical surgical margin (ASM) and apical soft
      tissue margin (ASTM), determine if the ASTM is a better predictor of biochemical
      recurrence (BR) than the ASM, and ascertain the impact of apical biopsies on BR
      rates. MATERIALS AND METHODS: One thousand three hundred eight consecutive men
      underwent open radical retropubic prostatectomy (RP) between October 2000 and
      December 2006. Circumferential biopsies of the ASTM were obtained
      intraoperatively and submitted for frozen section analysis. Logistic regression
      models were utilized to identify the factors associated with the presence of
      positive ASMs and ASTMs. The estimated 5-year risk of BR was calculated by the
      Kaplan-Meier method. RESULTS: Overall, 43 (3.3%) and 86 (6.6%) of cases exhibited
      positive ASM and ASTM, respectively. ASM was significantly associated with higher
      mean serum prostate-specific antigen levels, presence of perineural invasion, and
      greater volume of tumor in the biopsy specimen. None of these factors were
      observed to be associated with the presence of cancer in the ASTMs. In the
      multivariate analysis, only the presence of perineural invasion was a significant
      independent predictor of ASMs. The estimated 5-year BR rates in the positive ASMs
      only, ASTMs only, and both positive ASMs and ASTMs groups were 48.6%, 4.7%, and
      38.8%, respectively. CONCLUSIONS: A positive ASM was associated with a
      significantly greater risk of BR compared with a positive ASTM. The very low
      estimated risk of BR at 5 years in cases with ASTM suggests that performing the
      ASTM biopsies may increase the cure rates achieved with RP.

PMID- 19762255
TI  - The role of cell-free circulating DNA in the diagnosis and prognosis of prostate
      cancer.
AB  - The presence of small amounts of circulating DNA in plasma was demonstrated 60
      years ago. Since then, cell-free DNA has been tested for quantity, fragmentation
      pattern, and tumor-specific sequences in patients with various malignancies.
      Recent studies have shown that cell-free DNA levels are distinctly increased in
      most patients with prostate cancer (PCA) and that the DNA fragmentation pattern
      is different from healthy individuals and patients with benign prostate disease.
      The origin of this circulating DNA remains largely unknown, but it is established
      that a small fraction of the DNA is derived from the tumor itself, and genetic
      (allelic imbalances) and epigenetic (DNA methylation) alterations are regularly
      detected in patients with PCA. The detection of increased DNA levels and tumor
      specific DNA sequences may provide diagnostic and prognostic information. The
      recent findings in the emerging field of cell-free DNA will be discussed.

PMID- 19762256
TI  - Bladder recurrence after surgery for upper urinary tract urothelial cell
      carcinoma: frequency, risk factors, and surveillance.
AB  - OBJECTIVE: To highlight the main risk factors for metachronous bladder recurrence
      after treatment of an upper urinary tract urothelial cell carcinomas (UUT-UCCs)
      based on the recent literature. MATERIALS AND METHODS: Data on urothelial
      malignancies after UUT-UCCs management in the literature were searched using
      MEDLINE and by matching the following key words: urinary tract cancer; bladder
      carcinomas, urothelial carcinomas, upper urinary tract, renal pelvis, ureter
      prognosis, carcinoma, transitional cell, renal pelvis, ureter, bladder cancer,
      cystectomy, nephroureterectomy, minimally invasive surgery, recurrence, and
      survival. RESULTS: No evidence level 1 information from prospective randomized
      trials was available. A range of 15% to 50% of patients with a UUT-UCC will
      subsequently develop a metachronous bladder UCC. Intraluminal tumor seeding and
      pan-urothelial field change effect have both been proposed to explain
      intravesical recurrences. In most cases, bladder cancer arises in the first 2
      years after UUT-UCC management. However the risk is lifelong and repeat episodes
      are common. The identification of variables that allow accurate risk
      stratification of UUT-UCC patients with regards to future bladder relapse is
      disappointing. No factors have been identified to date that can reliably predict
      bladder recurrences. A history of bladder cancer prior to UUT-UCC management and
      upper tract tumor multifocality are the only frequently reported clinical risk
      factors among current literature. CONCLUSION: Prior histories of bladder cancer
      and upper tract tumor multifocality are the most frequently reported risk factors
      for bladder tumors following UUT-UCCs. Surveillance regimen is based on
      cystoscopy and on urinary cytology for at least 5 years.

PMID- 19762257
TI  - Human CD34+ cells are capable of generating normal and JAK2V617F positive
      endothelial like cells in vivo.
AB  - Endothelial like cells (ELCs) are thought to originate from either a hierarchy of
      endothelial progenitor cells (EPC), monocytes or monocyte derived multipotent
      progenitor cells (MOMCs). In this report, the ability of CD34(+) cells to
      generate ELC in vivo was examined using an immunodeficient mouse transplant assay
      system. The Philadelphia chromosome negative (Ph(-)) myeloproliferative neoplasms
      (MPN) are associated with the acquired mutation, JAK2V617F. In order to further
      examine the ability of cord blood and JAK2V617F positive MPN CD34(+) cells to
      generate ELC, CD34(+) cells were transplanted into NOD/SCID mice. Cells within
      the livers and lungs of recipient mice had phenotypic and molecular properties of
      human ELC as examined using RT-PCR, flow cytometric analysis and fluorescence
      microscopy. These cells possessed either human wild type JAK2 or JAK2V617F
      indicating that they were derived from the transplanted human cells and that a
      fraction of such cells were involved by the malignant process. Furthermore, human
      CD144(+) cells isolated from the livers of recipient mice formed clusters in
      vitro composed of ELC, which contained either wild type JAK2 or JAK2V617F
      suggesting that these cells are derived from either MOMC or EPC that have an
      extensive proliferative capacity as well as some degree of self renewal capacity.
      These studies indicate that adult CD34(+) cells can be affected by JAK2V617F and
      that they can generate ELC which might play a role in the development of
      thrombosis in patients with MPN.

PMID- 19762258
TI  - Classification of degraded cartilage through multiparametric MRI analysis.
AB  - MRI analysis of cartilage matrix may play an important role in early detection
      and development of therapeutic protocols for degenerative joint disease.
      Correlations between MRI parameters and matrix integrity have been established in
      many studies, but the substantial overlap in values observed for normal and for
      degraded cartilage greatly limits the specificity of these analyses. We
      implemented established multiparametric analysis methods to define data clusters
      corresponding to control and degraded bovine nasal cartilage in two-, three-, and
      four-dimensional parameter spaces, and applied these results to discriminant
      analysis of a validation data set. Analyses were performed using the parameters
      (T(1), T(2), k(m), ADC), where k(m) is the magnetization transfer rate and ADC is
      the apparent diffusion coefficient. Results were compared to univariate analyses.
      Multiparametric k-means clustering led to no improvement over univariate
      analyses, with a maximum sensitivity and specificity in the range of 60-70% for
      the detection of degradation using T(1), and in the range of 80% sensitivity but
      only 36% specificity using the parameter pair (T(1), k(m)). In contrast, model
      based analysis using more general Gaussian clusters resulted in markedly improved
      classification, with sensitivity and specificity reaching levels of 80-90% using
      the pair (T(1), k(m)). Finally, a fuzzy clustering technique was implemented
      which may be still more appropriate to the continuum of degradation seen in
      degenerative cartilage disease. In view of its success in identifying mild
      cartilage degradation, the formal multiparametric approach implemented here may
      be applicable to the nondestructive evaluation of other biomaterials using MRI.

PMID- 19762259
TI  - InCa-SiteFinder: a method for structure-based prediction of inositol and
      carbohydrate binding sites on proteins.
AB  - Carbohydrate binding sites are considered important for cellular recognition and
      adhesion and are important targets for drug design. In this paper we present a
      new method called InCa-SiteFinder for predicting non-covalent inositol and
      carbohydrate binding sites on the surface of protein structures. It uses the van
      der Waals energy of a protein-probe interaction and amino acid propensities to
      locate and predict carbohydrate binding sites. The protein surface is searched
      for continuous volume envelopes that correspond to a favorable protein-probe
      interaction. These volumes are subsequently analyzed to demarcate regions of high
      cumulative propensity for binding a carbohydrate moiety based on calculated amino
      acid propensity scores. InCa-SiteFinder(1) was tested on an independent test set
      of 80 protein-ligand complexes. It efficiently identifies carbohydrate binding
      sites with high specificity and sensitivity. It was also tested on a second test
      set of 80 protein-ligand complexes containing 40 known carbohydrate binders
      (having 40 carbohydrate binding sites) and 40 known drug-like compound binders
      (having 58 known drug-like compound binding sites) for the prediction of the
      location of the carbohydrate binding sites and to distinguish these from the drug
      like compound binding sites. At 73% sensitivity the method showed 98%
      specificity. Almost all of the carbohydrate and drug-like compound binding sites
      were correctly identified with an overall error rate of 12%.

PMID- 19762260
TI  - Phaeohyphomycotic osteomyelitis in the femur of a cat.
AB  - A 4-month-old castrated male domestic shorthair cat was presented for a right
      hind leg lameness of 1-week duration. Physical examination revealed a painful
      swelling over the right distal femur. A radiograph of the right stifle revealed
      an extensive lytic lesion involving the distal metaphysis of the right femur.
      Cytological examination of a needle aspirate was consistent with a deep fungal
      infection. A pigmented dimorphic fungus was isolated in pure culture from a
      representative needle aspirate from the lesion. The patient improved
      substantially after 5 weeks of high-dose itraconazole therapy, although it was
      subsequently lost to follow-up.

PMID- 19762261
TI  - Role of interleukin-12 family cytokines in the cellular response to mycobacterial
      disease.
AB  - Interleukin (IL)-12 is a multifunctional cytokine acting as a key regulator of
      cell-mediated immune responses through the differentiation of naive CD4+ T cells
      into type 1 helper T cells (Th1) producing interferon-gamma. As our knowledge of
      IL-12 family members is rapidly growing, it will be important to specify their
      involvement in the regulation of mycobacterial infection. This article is a
      review of the current knowledge regarding the functions of the IL-12 family
      cytokines in the immune host defense system against mycobacteria. Specifically,
      this review aims to describe recent scientific evidence concerning the protective
      role of some members of the IL-12 family cytokines for the control of
      mycobacterial infection, as well as to summarize knowledge of the potential use
      of the IL-12 family members as potent adjuvants in the prevention and treatment
      of mycobacterial infectious diseases. In addition, recent data supporting the
      importance of the IL-12 family members in mycobacterial diseases in relation to
      Th17 function are discussed. This examination will help to improve our
      understanding of the immune response to mycobacterial infection and also improve
      vaccine design and immunotherapeutic intervention against tuberculosis.

PMID- 19762262
TI  - [Three-dimensional brachytherapy optimization techniques in the treatment of
      patients with cervix cancer].
AB  - Traditionally, prescription and treatment planning in intracavitary brachytherapy
      for cervix cancer have used either reference points (mainly points A and B) or
      reference isodoses (60Gy according to ICRU recommendations) to report doses to
      the target volume. Doses to critical organs were reported at bladder and rectum
      ICRU points. This practice has been supported by a long-standing clinical
      experience that has yielded an acceptable therapeutic ratio. The recent
      development of imaging has contributed to the improvement in target and organs at
      risk knowledge. In 2005 and 2006, GEC-ESTRO recommendations publications on 3-D
      based image brachytherapy have defined the different volumes of interest. These
      recommendations have been validated with intercomparison delineation studies.
      With the concomitant development of remote after-loading projectors, provided
      with miniaturized sources, it is now possible to plan radiation doses by
      adjusting dwell positions and relative dwell time values. These procedures allow
      better coverage of the targets while sparing OAR. The recent literature data
      evidence a significant improvement in local control with no increase in
      complications. Further studies are needed to better define the dose recommended
      in both tumour and organs at risk. This is one of the goals of the European study
      on MRI-guided brachytherapy in locally advanced cervical cancer (EMBRACE)
      protocol.

PMID- 19762263
TI  - [Stereotactical radiotherapy in pediatrics indications].
AB  - Stereotactical radiotherapy is a very high precision procedure, limited to
      radiosurgery since a long time. Technologic progress permitted to develop
      radiotherapy in stereotactical conditions, leading to a lot of innovations.
      Previously indicated for cerebral pathologies, this procedure is now developed
      for extracerebral locations. In pediatrics, stereotactical radiotherapy is still
      limited, delivered precociously, due to the possibility of long-term late effects
      that needs to be to addressed. This review reports the different useful
      conditions, technical evolutions, and the current validated pediatric
      indications, with differences from adults, and future directions. Current state
      of pediatric stereotactical radiotherapy used in France is presented.

PMID- 19762264
TI  - Normal range-of-motion of trapeziometacarpal joint.
AB  - PURPOSE: The range-of-motion of the trapeziometacarpal joint is difficult to
      assess clinically. The purpose of our study was to constitute a range-of-motion
      database from normal active trapeziometacarpal joints. MATERIAL AND METHODS: Two
      hundred hands from 101 healthy subjects (50 female and 51 male) with a mean age
      of 23.1 years (range: 22 to 35 years) have been evaluated. An optoelectronic
      device (Polaris) was used to analyse the thumbs range-of-motion. Splints were
      fitted so as to isolate the trapeziometacarpal joint and retroreflective markers
      were placed both on the splints and on the thumb. After active flexion-extension,
      abduction-adduction, axial rotation and circumduction, the different range-of
      motion parameters were calculated. RESULTS: The mean range-of-motion of the
      trapeziometacarpal joint was 41 degrees for flexion-extension, 51 degrees for
      abduction-adduction and 21 degrees for axial rotation. Comparisons between female
      and male subjects showed significant differences concerning flexion-extension,
      abduction-adduction axial rotation and circumduction. No significant differences
      were noted between right and left hands except for the abduction-adduction
      movement. DISCUSSION AND CONCLUSION: One hundred and one healthy subjects were
      analysed for the development of a database of normal active range-of-motion
      parameters of the trapeziometacarpal joint, with an in vivo protocol. This
      database should allow comparing the range-of-motion of patients with
      osteoarthritic trapeziometacarpal joint and assessing surgical outcome.

PMID- 19762265
TI  - [Traumatic avulsion of the flexor digitorum profundus tendon. Report of 20
      cases].
AB  - Traumatic avulsion of the flexor digitorum profundus tendon or "jersey" finger is
      uncommon. Twenty patients have been reviewed at an average follow-up of seven
      years. Patients were seen less than three weeks from trauma in two-thirds of the
      cases, whereas in one third it was later. Loss of active flexion of the distal
      interphalangeal joint was the main complaint. Pure avulsions seen less than three
      weeks from the injury were all reinserted except one (10 out of 11). When the
      tendon avulsion was associated with a bone fragment (three cases), an
      osteosynthesis with K-wires was performed. Patients seen more than three weeks
      from the injury were treated with tendon resection in six, with a capsulodesis in
      four, and with a palmaris longus tendon graft in one. All reinsertions of the
      flexor digitorum profundus tendon performed less than three weeks from injury
      gave satisfactory results but a secondary rupture was observed in two.
      Satisfactory results were also obtained after avulsion of the tendon associated
      with bone fracture, but one patient developed osteoarthritis. Three out of five
      patients operated more than three weeks following the injury with tendon
      resection had satisfactory results. The patient with a palmaris longus tendon
      graft obtained an unsatisfactory result.

PMID- 19762266
TI  - Syntheses and characterization of Mg(OH)(2) and MgO nanostructures by ultrasonic
      method.
AB  - Magnesium hydroxide nanostructures have been synthesized by the reaction of
      magnesium acetate with sodium hydroxide via sonochemical method. Reaction
      conditions such as the Mg(2+) concentration, aging time and the ultrasonic device
      power show important roles in the size, morphology and growth process of the
      final products. The magnesium oxide nanoparticles have been prepared by
      calcination of magnesium hydroxide nanostructures at 400 degrees C. The magnesium
      hydroxide and magnesium oxide nanostructures were characterized by scanning
      electron microscopy (SEM), X-ray powder diffraction (XRD), thermal gravimetric
      (TG) and differential thermal analyses (DTA).

PMID- 19762267
TI  - Preparation of hydrogels via ultrasonic polymerization.
AB  - Several acrylic hydrogels were prepared via ultrasonic polymerization of water
      soluble monomers and macromonomers. Ultrasound was used to create initiating
      radicals in viscous aqueous monomer solutions using the additives glycerol,
      sorbitol or glucose in an open system at 37 degrees C. The water soluble
      additives were essential for the hydrogel production, glycerol being the most
      effective. Hydrogels were prepared from the monomers 2-hydroxyethyl methacrylate,
      poly(ethylene glycol) dimethacrylate, dextran methacrylate, acrylic acid/ethylene
      glycol dimethacrylate and acrylamide/bis-acrylamide. For example a 5% w/w
      solution of dextran methacrylate formed a hydrogel in 6.5min in a 70% w/w
      solution of glycerol in water at 37 degrees C with 20kHz ultrasound, 56Wcm(-2).
      The ultrasonic polymerization method described here has a wide range of
      applications such a biomaterial synthesis where initiators are not desired.

PMID- 19762268
TI  - Ultrasound promoted one-pot synthesis of 3-aza-6,10-diaryl-2-oxa-spiro[4.5]decane
      1,4,8-trione.
AB  - One-pot synthesis of 3-aza-6,10-diaryl-2-oxa-spiro[4.5]decane-1,4,8-trione from
      1,5-diaryl-1,4-pentadien-3-one can be carried out in good yields at 50 degrees C
      under ultrasound irradiation. This method provided several advantages such as
      simple work-up procedure, shorter reaction time and higher yield.

PMID- 19762269
TI  - Experimental validation of the nerve conduction velocity selective recording
      technique using a multi-contact cuff electrode.
AB  - The earthworm (Lumbricus terrestris) is presented as an in vitro model of a
      peripheral nerve containing only two fibers each with distinctly different
      conduction velocities, the median and lateral giant fibers (MGF and LGF). The
      worm model is used with a multi-contact cuff electrode to validate the spatial
      temporal filtering effect of different electrode contact configurations and the
      effect of applying a delay adder and matched filter tuned to either the MGF or
      LGF action potential (AP) to extract conduction direction and velocity from the
      recording. The results confirmed the known effect of inter-electrode spacing and
      bipolar and tripolar recording configuration on the AP amplitude. It also
      demonstrates a crossover point where the amplitude of the tripolar recording is
      larger than the monopolar recording, an effect of the slower action potential
      conduction velocities in the worm. The delay adder was found to be an effective
      velocity sensitive filter, able to discriminate units based on conduction
      velocity. The matched filter to be an effective means to eliminate artifact and
      increase signal to noise ratios, however was not found to improve selectivity.

PMID- 19762270
TI  - Partial potentials of selected cardiac muscle regions and heart activity model
      based on single fibres.
AB  - We present single fibre heart activity model (SFHAM) based on the current flow
      through the five bunches of fibres of the cardiac muscle (CM). The five effective
      fibres are identified and assigned to the appropriate segments of CM. Analytical
      functions describing ionic flows along the fibres are derived and proposed. The
      parameters determining the shapes and amplitudes of the functions proposed are
      obtained on the basis of standard 12-lead ECG measurements after numerical
      fitting procedures concentrating on the QRS-waves. As a consequence, five
      independent courses of partial, transient potentials are obtained representing:
      anterior, inferior, lateral, posterior walls, and interventricular septum
      activities, respectively. Moreover, to check our theoretical results we compare
      the potentials calculated with those from physical measurements performed on the
      patient's body surface. We expect that SFHAM will permit detection of
      pathological changes in particular fragments of CM.

PMID- 19762271
TI  - Eighteen month study of continuous intraduodenal levodopa infusion in patients
      with advanced Parkinson's disease: impact on control of fluctuations and quality
      of life.
AB  - Symptom control, daily "on" time, and quality of life (QoL) of nine patients with
      Advanced Parkinson's Disease was assessed following 18-months treatment with
      Continuous Intraduodenal Levodopa Infusion (CIDLI). Patients had severe motor
      fluctuations and dyskinesias and had previously received treatment with oral
      levodopa and dopamine agonists. There were significant improvements in patients'
      symptoms on the Unified Parkinson's Disease Rating Scale, and QoL (Parkinson's
      Disease QoL Questionnaire; Schwab & England Capacity for Daily Living Scale; p <
      0.05). Mean (+/-SD) daily "on" time increased from 6.1 +/- 1.9 to 12.0 +/- 3.4 h
      (p < 0.05). Improved QoL in APD was associated with CIDLI-related improvements in
      symptom control and increase in daily "on" time.

PMID- 19762272
TI  - Social class differences in health behaviours among employees from Britain,
      Finland and Japan: the influence of psychosocial factors.
AB  - This study aims to examine social class differences in smoking, heavy drinking,
      unhealthy food habits, physical inactivity and obesity, and work-related
      psychosocial factors as explanations for these differences. This is done by
      comparing employee cohorts from Britain, Finland and Japan. Social class
      differences in health behaviours are found in the two western European countries,
      but not in Japan. The studied psychosocial factors related to work, work-family
      interface and social relationships did not explain the found class differences in
      health behaviours.

PMID- 19762273
TI  - Direct methods for studying transcription regulatory proteins and RNA polymerase
      in bacteria.
AB  - Transcription factors and sigma factors play a major role in bacterial gene
      regulation by guiding the distribution of RNA polymerase between the promoters of
      different transcription units in response to changes in the environment. For 40
      years Escherichia coli K-12 has been the paradigm for investigating this
      regulation and most studies have focused on small numbers of promoters studied by
      a combination of genetics and biochemistry. Since the first complete sequence for
      a bacterial genome was reported, the emphasis has switched to studying
      transcription on a global scale, with transcriptomics and bioinformatics becoming
      the methods of choice. Here we discuss two complementary direct experimental
      methods for studying transcription factors and sigma factors and we outline their
      potential use in rapidly establishing the regulatory networks in newly sequenced
      bacteria.

PMID- 19762274
TI  - 31P NMR study of the stoichiometry, stability and thermodynamics of complex
      formation between palladium(II) acetate and bis(diphenylphosphino)ferrocene.
AB  - The complexation reaction between palladium (II) acetate, and 1,1'
      bis(diphenylphosphino)ferrocene, DPPF, was investigated in two different
      deuterated solvents CDCl(3) and DMSO at various temperatures using (31)P NMR
      spectroscopy. The exchange between free and complexed DPPF is slow on the NMR
      time scale and consequently, two (31)P NMR signals were observed. At metal ion-to
      ligand mole ratio larger than 1, only one (31)P NMR signal was observed,
      indicating the formation of a 1:1 Pd(2+)-DPPF complex in solution. The formation
      constant of the resulting 1:1 complexes was determined from the integration of
      two (31)P signals. The values of the thermodynamic parameters (DeltaH, DeltaS and
      DeltaG(298)) for complexation were determined from the temperature dependence of
      stability constants. It was found that, in both solvents, the resulting complex
      is mainly entirely enthalpy stabilized and the DeltaH compensates the TDeltaS
      contribution.

PMID- 19762275
TI  - From salmon pink to blue natural sensitizers for solar cells: Canna indica L.,
      Salvia splendens, cowberry and Solanum nigrum L.
AB  - Study on dye-sensitized solar cells (DSSCs) with extracts of Canna indica L.,
      Salvia splendens, Solanum nigrum L. as sensitizers is firstly reported in this
      paper. DSSCs were assembled by using natural dyes extracted from C. indica L., S.
      splendens, cowberry and S. nigrum L. as sensitizers. The energy conversion
      efficiency of the cells sensitized with dyes of C. indica L., S. splendens,
      cowberry and S. nigrum L. was 0.29%, 0.26%, 0.13% and 0.31%, respectively. A
      novel technique was taken to fabricate TiO(2) electrode films by electrophoresis.
      We present FTIR and UV-vis spectroscopy studies of structures and light
      absorption of these four kinds of natural dyes. The electrochemical impedance
      spectroscopy (EIS) was used to analyze the interface resistance of cells. The
      result indicated that high resistance existed in the interfaces of cell with
      cowberry extract as sensitizer.

PMID- 19762276
TI  - High test-retest reliability of checkerboard reversal visual evoked potentials
      (VEP) over 8 months.
AB  - OBJECTIVE: The inter-individual variation in the shape of a visual evoked
      potential (VEP) is large even for simple stimuli. We compared the inter
      individual variation in VEP waveform to the intra-individual stability. METHODS:
      We recorded VEP with checkerboard stimulation in 10 women aged 19-29years in two
      sessions. We determined the latencies and the peak-to-peak amplitude of N75 and
      P100. As a new approach in VEP research, we regressed VEP waveforms pairwise onto
      each other and calculated a t-value between all sessions. The maximal t-value was
      taken to indicate recognition for all 19 comparisons performed with one session.
      The recognition rate was cross-validated in a generalized linear regression model
      (GLM). RESULTS: The number of sessions correctly matched to the correct subject
      was 19 of 20 (true positives) leading to a sensitivity of 95.0% with confidence
      interval [75.1% 99.9%] for the method. The number of true negatives was 359 of
      360 leading to a specificity of 99.7% [98.5% 100.0%]. CONCLUSIONS: The VEP
      waveform shows high intra-individual stability compared to the inter-individual
      variation in healthy women. SIGNIFICANCE: With a new statistical approach the
      effect of external factors on the VEP waveform can now be contrasted against the
      normal variability over time in longitudinal studies.

PMID- 19762277
TI  - Contingent negative variations associated with command swallowing in humans.
AB  - OBJECTIVE: To clarify the role of the cerebral cortex in the swallowing movement,
      the difference between the waveforms of contingent negative variation (CNV) for
      the command swallowing and movement-related cortical potential (MRCP) obtained
      during the volitional swallowing task in humans was investigated. METHODS:
      Subjects were instructed to swallow their saliva as quickly as possible in
      response to a sound signal 4s after the onset of a self-paced breath holding in
      the command swallowing task or to swallow it while holding their breath for 4s in
      the volitional swallowing task. RESULTS: CNV and MRCP appeared at five recording
      areas 1.5 and 2.0s before the onset of the suprahyoid muscle activation
      determined by the electromyography (EMG) during the command swallowing and
      volitional swallowing tasks, respectively. The CNV amplitude during the command
      swallowing task was significantly higher than the MRCP amplitude during the
      volitional swallowing task (p<0.01). However, the suprahyoid muscle activities
      during both tasks were not significantly different (p>0.05). CONCLUSIONS: These
      results indicated that CNV may reflect the activities of the prefrontal cortex,
      in addition to the supplementary motor area, suggesting that the processing of
      the cue to swallow activates brain areas more widely than the volitional
      swallowing itself. SIGNIFICANCE: It is possible to clarify the cognitive
      functions associated with command swallowing by analyzing CNV.

PMID- 19762278
TI  - Temporal resolution in swallowing neural control: the way forward.

PMID- 19762280
TI  - Are neutrophils important host cells for Leishmania parasites?
AB  - Neutrophils are the most crucial cells for early defence against infections. When
      appropriately activated, they can kill obligate intracellular pathogens such as
      Leishmania. However, once the phagocytotic killing has been evaded, neutrophils
      can serve as host cells for Leishmania. Parasitized neutrophils were suggested to
      function as a 'Trojan horse', to transfer Leishmania silently to macrophages. In
      vivo imaging has contributed a second evasion mechanism. We termed it the 'Trojan
      rabbit' strategy, whereby parasites escape dying neutrophils to infect
      macrophages. Here, we discuss the different experimental models used to study
      neutrophil function in leishmaniasis. We suggest that the capacity of neutrophils
      to function as an immune evasion target depends on the genetic background of the
      host and the parasite strain used for the experiments.

PMID- 19762279
TI  - Hepatitis C: recent successes and continuing challenges in the development of
      improved treatment modalities.
AB  - Dramatic progress is being made toward the development of less-toxic and simpler
      alternatives to the current standard-of-care therapy for chronic hepatitis C,
      which involves a combination of pegylated interferon (peg-IFN) and ribavirin
      (RBV). Several accessible viral targets have been identified and licensure of the
      most advanced clinical compounds can be anticipated within the next several
      years. However, the highly replicative nature of HCV infection, coupled with
      error-prone viral RNA synthesis and considerable genome diversity, pose
      extraordinary challenges to drug development. Peg-IFN is likely to remain a
      mainstay of therapy for the foreseeable future, or until such time that multiple
      direct-acting antiviral (STAT-C) inhibitors are available and shown to provide a
      sufficiently high barrier to resistance when used in combination.

PMID- 19762281
TI  - Oestrid flies: eradication and extinction versus biodiversity.
AB  - Larvae of oestrid flies are obligate parasites of mammals. This article focuses
      on two potential drivers that could be forcing these flies into extinction: (i)
      the highly effective and widespread use of anti-parasitic drugs for domestic
      livestock; and (ii) the co-extinction of oestrids associated with non-domestic
      hosts that are endangered. Other oestrid species could be the victims of benign
      neglect in that they are so poorly studied that their disappearance might go
      unnoticed. In addition, we explore current knowledge in each of these categories
      of vulnerability for oestrids, and address the potential impacts of their
      disappearance. Finally, we examine the potential consequences of eradicating a
      group of livestock parasites, and ask what possibilities for improvement of the
      health of humans and animals might also be lost.

PMID- 19762282
TI  - Behavior of non-classical soluble HLA class G antigens in human immunodeficiency
      virus 1-infected patients before and after HAART: comparison with classical
      soluble HLA-A, -B, -C antigens and potential role in immune-reconstitution.
AB  - We have reported that serum level of soluble HLA-A, -B, -C (sHLA-A,-B,-C)
      antigens is elevated in HIV-infected subjects and decreases after antiretroviral
      therapy (HAART). In this study, we measured the levels of soluble HLA-G (sHLA-G)
      antigens in a cohort of HIV-infected patients before and during HAART. sHLA-G and
      sHLA-A, -B, -C levels were significantly elevated in HIV-infected subjects as
      compared with controls before antiretroviral treatment and significantly
      decreased after 36 months of HAART. sHLA-G levels were correlated with sHLA-A, 
      B, -C levels, the decrease of plasma HIV-RNA level, the increase of CD4+ T
      lymphocyte number and the decrease of CD8+ T-lymphocyte number. These results
      suggest that the measurement of sHLA-G and sHLA-A, -B, -C antigen serum levels
      might represent a useful surrogate marker to monitor virological response and
      immune reconstitution in HIV-positive subjects undergoing HAART treatment.

PMID- 19762284
TI  - Seizure control with thermal energy? Modeling of heat diffusivity in brain tissue
      and computer-based design of a prototype mini-cooler.
AB  - Automated seizure blockage is a top priority in epileptology. Lowering nervous
      tissue temperature below a certain level suppresses abnormal neuronal activity,
      an approach with certain advantages over electrical stimulation, the preferred
      investigational therapy for pharmacoresistant seizures. A computer model was
      developed to identify an efficient probe design and parameters that would allow
      cooling of brain tissue by no less than 21 degrees C in 30s, maximum. The Pennes
      equation and the computer code ABAQUS were used to investigate the spatiotemporal
      behavior of heat diffusivity in brain tissue. Arrays of distributed probes
      deliver sufficient thermal energy to decrease, inhomogeneously, brain tissue
      temperature from 37 to 20 degrees C in 30s and from 37 to 15 degrees C in 60s.
      Tissue disruption/loss caused by insertion of this probe is considerably less
      than that caused by ablative surgery. This model may be applied for the design
      and development of cooling devices for seizure control.

PMID- 19762285
TI  - Genetically inbred Balb/C mice are more sensitive to an effect of flurazepam and
      more resistant to an effect of stress than a genetically outbred mouse strain.
AB  - The inbred Balb/c mouse strain was more sensitive than the outbred NIH Swiss
      mouse to flurazepam's ability to antagonize electrically precipitated seizures.
      In prior work, a reduction in flurazepam's antiseizure efficacy was not observed
      24h after forcing Balb/c mice to swim for up to 10 min in ambient temperature
      water. Thus, we wondered if a stress-induced reduction would be observed after
      forcing mice to swim for up to 10 min in cold (6 degrees C) water, a more severe
      stress. The current data show that 24 h after exposure to this stress, the
      ability of flurazepam to raise the threshold voltage for the elicitation of tonic
      hindlimb extension in the Balb/c mouse strain was reduced. The genetically inbred
      Balb/c mouse strain is emerging as an interesting animal model in which to study
      interactions of stress and genetic factors that affect endogenous
      neurotransmission mediated by l-glutamate and GABA at the NMDA and GABA(A)
      receptor complexes, respectively.

PMID- 19762283
TI  - Autologous MUC1-specific Th1 effector cell immunotherapy induces differential
      levels of systemic TReg cell subpopulations that result in increased ovarian
      cancer patient survival.
AB  - Adoptive T cell immunotherapy using autologous lymphocytes is a viable treatment
      for patients with cancer and requires participation of Ag-specific CD4 and CD8 T
      cells. Here, we assessed the immunotherapeutic effects of autologous MUC1 peptide
      stimulated CD4(+) effector cells following adoptive transfer in patients with
      ovarian cancer. Using MUC1 peptide and IL-2 for ex vivo CD4(+)/Th1 effector cell
      generation, we show that three monthly treatment cycles of peripheral blood T
      cell restimulation and intraperitoneal re-infusion selectively modulated
      endogenous T cell-mediated immune responses that correlated with diminished serum
      CA125 tumor marker levels and enhanced patient survival. One patient remains
      disease-free, another patient survived long-term for nearly 16 months with
      recurrent disease and two patients expired within 3-5 months following final
      infusion. Although PBL from all patients showed elevated MUC1 cytolytic activity
      following therapy, such responses did not correlate with therapeutic efficacy.
      Long-term survivors showed elevated levels of systemic memory (CD45RO) and naive
      (CD45RA) CD3/CD4/CD25(+) T cells when compared to that of pre-treatment levels
      and similarly treated short-term survivors. Such cells co-expressed different
      levels of Foxp3 and CTLA-4 that resulted in progressively lower systemic
      Foxp3/CTLA-4 memory T cell ratios that further correlated with disease-free
      survival. Lastly, these patients showed elevated levels of MUC1-specific T cells
      expressing the CCR5 and CCR1 chemokine receptors and the chemokine CCL4
      associated with Th1 cell differentiation/memory. We suggest that effective
      immunotherapy with autologous MUC1-stimulated CD4(+) effector cells induces
      differential levels of systemic "Ag-experienced" and "Ag-inexperienced"
      CD4/CD25(+) TReg cell subpopulations that influence long-term tumor immunity in
      ovarian cancer patients.

PMID- 19762286
TI  - AnchorSeed for the reduction of source movement in prostate brachytherapy with
      the Mick applicator implant technique.
AB  - PURPOSE: The purpose of this study was to evaluate the influence of potential
      contributing factors to the incidence of seed slippage and quality of prostate
      brachytherapy dosimetry comparing "coated" vs. "bare" seeds with a Mick
      applicator. METHODS AND MATERIALS: Two consecutive groups of 89 patients were
      treated with (125)I prostate brachytherapy at a high treatment volume single
      institution. All the patients were evaluated with Day 0 plain films of the pelvis
      and CT-based dosimetry analysis. The incidence of seed slippage was quantified.
      The seed slippage outcome was evaluated with respect to source type (bare vs.
      coated). The Day 0 prostate V(100), V(150), D90%, rectal V(100), and urethra
      D(30) outcomes were evaluated with respect to source type. RESULTS: A total of
      13,512 seeds were placed in 178 patients. An average of 76 seeds and 16 needles
      were used for each patient. The bare seed group was significantly higher on
      fluoroscopy minutes (2.34 vs. 1.58 min), seed slippage (5 vs. 1.5 mm), volume of
      rectum receiving 100% of dose (0.05 vs. 0.0 cc), dose percentage received by 30%
      of urethra (119% vs. 113.64%), and volume of prostate receiving 100% of
      prescription dose (95.21% vs. 92.8%). No significant differences in volume of
      prostate receiving 150% of prescription dose, dose percentage received by 90% of
      prostate, vascular seed migration, or operating room procedure time were seen. No
      seed drift greater than 10mm outside the "packet" of other seeds was seen in the
      AnchorSeed (BrachySciences, a division of Biocompatibles, Inc. Oxford, CT)
      cohort. CONCLUSION: The report is the first to show the unique "fixity" of
      AnchorSeed to remain in position after deployment from the Mick applicator.
      Minimizing seed drag can reduce dose to the penile bulb, and maximize radiation
      coverage to the apex of the gland.

PMID- 19762287
TI  - Carbon nanotube-hydroxyapatite-hemoglobin nanocomposites with high
      bioelectrocatalytic activity.
AB  - In this paper, carbon nanotubes-hydroxyapatite (MWCNTs-HA) composite were
      synthesized by self-assembling technique, and investigated by X-ray diffraction,
      scanning electron microscopy (SEM) and FT-IR spectroscopy. Hemoglobin (Hb)
      immobilized in MWCNTs-HA film not only retained its similarly native
      conformations, but also achieved the direct electron transfer. The apparent
      heterogeneous electron transfer rate constant (k(s)) was evaluated as (5.05+/
      0.41) s(-1) according to Laviron's equation, and the surface coverage (Gamma*)
      was estimated as (9.25+/-0.69)x10(-10)mol cm(-2). Moreover, the Hb immobilized in
      MWCNTs-HA film exhibited remarkable bioelectrocatalytic activity for the
      electrochemical reduction of H(2)O(2). The amperometric response of the biosensor
      varied linearly with the H(2)O(2) concentration ranging from 0.5microM to
      2microM, and the results showed a detection limit of 0.09microM. Furthermore, the
      Hb-immobilized MWCNTs-HA film exhibited the excellent catalytic reactivity toward
      trichloroacetic acid (TCA).

PMID- 19762288
TI  - The unstructured C-terminal extension of UvrD interacts with UvrB, but is
      dispensable for nucleotide excision repair.
AB  - During nucleotide excision repair (NER) in bacteria the UvrC nuclease and the
      short oligonucleotide that contains the DNA lesion are removed from the post
      incision complex by UvrD, a superfamily 1A helicase. Helicases are frequently
      regulated by interactions with partner proteins, and immunoprecipitation
      experiments have previously indicated that UvrD interacts with UvrB, a component
      of the post-incision complex. We examined this interaction using 2-hybrid
      analysis and surface plasmon resonance spectroscopy, and found that the N
      terminal domain and the unstructured region at the C-terminus of UvrD interact
      with UvrB. We analysed the properties of a truncated UvrD protein that lacked the
      unstructured C-terminal region and found that it showed a diminished affinity for
      single-stranded DNA, but retained the ability to displace both UvrC and the
      lesion-containing oligonucleotide from a post-incision nucleotide excision repair
      complex. The interaction of the C-terminal region of UvrD with UvrB is therefore
      not an essential feature of the mechanism by which UvrD disassembles the post
      incision complex during NER. In further experiments we showed that PcrA helicase
      from Bacillus stearothermophilus can also displace UvrC and the excised
      oligonucleotide from a post-incision NER complex, which supports the idea that
      PcrA performs a UvrD-like function during NER in gram-positive organisms.

PMID- 19762289
TI  - Mass spectral characterization of organophosphate-labeled, tyrosine-containing
      peptides: characteristic mass fragments and a new binding motif for
      organophosphates.
AB  - We have identified organophosphorus agent (OP)-tyrosine adducts on 12 different
      proteins labeled with six different OP. Labeling was achieved by treating pure
      proteins with up to 40-fold molar excess of OP at pH 8-8.6. OP-treated proteins
      were digested with trypsin, and peptides were separated by HPLC. Fragmentation
      patterns for 100 OP-peptides labeled on tyrosine were determined in the mass
      spectrometer. The goals of the present work were (1) to determine the common
      features of the OP-reactive tyrosines, and (2) to describe non-sequence MSMS
      fragments characteristic of OP-tyrosine peptides. Characteristic ions at 272 and
      244 amu for tyrosine-OP immonium ions were nearly always present in the MSMS
      spectrum of peptides labeled on tyrosine by chlorpyrifos-oxon. Characteristic
      fragments also appeared from the parent ions that had been labeled with
      diisopropylfluorophosphate (216 amu), sarin (214 amu), soman (214 amu) or FP
      biotin (227, 312, 329, 691 and 708 amu). In contrast to OP-reactive serines,
      which lie in the consensus sequence GXSXG, the OP-reactive tyrosines have no
      consensus sequence. Their common feature is the presence of nearby positively
      charged residues that activate the phenolic hydroxyl group. The significance of
      these findings is the recognition of a new binding motif for OP to proteins that
      have no active site serine. Modified peptides are difficult to find when the OP
      bears no radiolabel and no tag. The characteristic MSMS fragment ions are
      valuable because they are identifiers for OP-tyrosine, independent of the
      peptide.

PMID- 19762290
TI  - Biopharmaceutical production: Applications of surface plasmon resonance
      biosensors.
AB  - Surface plasmon resonance (SPR) permits the quantitative analysis of therapeutic
      antibody concentrations and impurities including bacteria, Protein A, Protein G
      and small molecule ligands leached from chromatography media. The use of surface
      plasmon resonance has gained popularity within the biopharmaceutical industry due
      to the automated, label free, real time interaction that may be exploited when
      using this method. The application areas to assess protein interactions and
      develop analytical methods for biopharmaceutical downstream process development,
      quality control, and in-process monitoring are reviewed.

PMID- 19762291
TI  - Joint GC-MS and LC-MS platforms for comprehensive plant metabolomics:
      repeatability and sample pre-treatment.
AB  - Metabolomics nowadays mostly comprises the application of both LC-MS and GC-MS
      based approaches. Here we investigate different extraction set-ups for these two
      established analytical platforms in the field of plant metabolomics. Six
      extraction approaches for Arabidopsis thaliana leaves, varying in extraction
      solvent composition, extraction temperature and order of solvent addition within
      the extraction sequence, were analyzed on the two platforms. Our aim was to
      establish the most suitable analysis protocol, practicable for both LC-MS and GC
      MS analysis, in order to obtain as extensive as possible metabolome coverage. One
      single sample preparation procedure would save time and valuable sample while
      still offering the complementary datasets generated by GC-MS and LC-MS. All
      extraction approaches were evaluated based on the following criteria: number of
      detected m/z-retention time pairs, heat maps of the detected peaks, and residual
      enzymatic activity of invertase and phosphatase in the plant leaf extracts.
      Unsupervised principal component analysis (PCA) was used to evaluate grouping
      trends between the different extraction approaches. Quality controls, a blend of
      aliquots of the different extracts, were used to establish a paired evaluation of
      the repeatability performance of the GC-MS and LC-MS analysis. We conclude that
      the use of chloroform in the extraction solvent is counterproductive in an
      untargeted LC-MS metabolomics approach as is heating. Below room temperature
      (instead of heated) extraction does not significantly degrade GC-MS performance
      but one should be more cautious with respect to residual enzymatic activity in
      the plant extract.

PMID- 19762292
TI  - Development and validation of a semi-automated assay for the highly sensitive
      quantification of Biolimus A9 in human whole blood using high-performance liquid
      chromatography-tandem mass spectrometry.
AB  - Drug-eluting stents are sustained-release intra-coronary devices that are usually
      coated with a few hundred micrograms of drug. Measuring the drugs that are
      released over weeks in order to assess human pharmacokinetics is a challenge that
      requires assays with high sensitivity. We developed and validated a semi
      automated LC-MS/MS assay for the quantification of Biolimus A9, a proliferation
      signal inhibitor that was specifically developed for coating on drug-eluting
      stents in human EDTA blood. The only manual step was the addition of a zinc
      sulfate/methanol protein precipitation solution which included the internal
      standard. Samples were injected into the HPLC and extracted online. The assay had
      the following performance characteristics: range of reliable response 0.01-100
      ng/mL (r(2)>0.99), inter-day accuracy (0.033 ng/mL): 111.7%, and inter-day
      precision: 8.6%. There was no ion suppression, matrix interferences or carry
      over. Extracted samples were stable in the autosampler at +4 degrees C for at
      least 24 h and could undergo three freeze-thaw cycles. The assay, with a lower
      limit of detection of 333 fg/mL and a lower limit of quantitation of 10 pg/mL,
      was sufficiently sensitive and robust for quantifying Biolimus A9 in clinical
      trials after i.v. injection and after stent implantation.

PMID- 19762293
TI  - A validated assay for the quantitative analysis of vatalanib in human EDTA plasma
      by liquid chromatography coupled with electrospray ionization tandem mass
      spectrometry.
AB  - A sensitive and accurate method for the determination of vatalanib in human EDTA
      plasma was developed using high-performance liquid chromatography and detection
      with tandem mass spectrometry. Stable isotopically labeled imatinib was used as
      internal standard. Plasma proteins were precipitated and an aliquot of the
      supernatant was directly injected onto a Phenomenex Gemini C18 analytical column
      (50 mm x 2.0 mm ID, 5.0 microm particle size) and then compounds were eluted with
      a linear gradient. The outlet of the column was connected to a Sciex API 365
      triple quadrupole mass spectrometer and ions were detected in positive multiple
      reaction monitoring mode. The lower limit of quantification was 10 ng/mL (S/N
      approximately 10, CV < or = 8.4%). This method was validated over a linear range
      from 10 to 2500 ng/mL, and results from the validation study demonstrated a good
      intra- and inter-assay accuracy (inaccuracy < or = 9.57%) and precision (CV < or
      = 8.81%). This method has been used to determine plasma vatalanib concentrations
      in patients with advanced solid tumor, enrolled in a phase I pharmacokinetic
      trial with the drug.

PMID- 19762294
TI  - Enrichment and properties of urinary pre-S-phenylmercapturic acid (pre-SPMA).
AB  - In benzene metabolism, pre-S-phenylmercapturic acid (pre-SPMA) is the precursor
      to S-phenylmercapturic acid (SPMA). Urinary pre-SPMA/SPMA ratios are variable.
      For the determination of urinary SPMA as a biomarker of exposure to benzene it is
      essential to completely convert pre-SPMA to SPMA. We developed a procedure for
      the enrichment and determination of urinary pre-SPMA by LC-MS/MS which allowed us
      to trace the conversion of pre-SPMA to SPMA. Complete conversion was found upon
      treatment of urine with HCl (37%) at pH 1.1. Previously reported treatment of
      urine with concentrated H(2)SO(4) was found to yield SPMA levels higher than
      after HCl treatment. The origin of that extra SPMA amount is unknown. In
      conclusion, our findings suggest that pre-treatment of urine with HCl to adjust
      the pH to 0.5-1 is essential for complete conversion of pre-SPMA to SPMA and
      should be applied prior to analysis of SPMA in urine.

PMID- 19762295
TI  - [Analgesic effect of breastfeeding when taking blood by heel-prick in newborns].
AB  - OBJECTIVE: To compare the analgesic effectiveness of breastfeeding when taking
      blood by the heel-lance procedure in healthy newborns, as opposed to other
      procedures. PATIENTS AND METHODS: We studied 228 term infants from the Maternity
      Unit of our Hospital. The study was developed in two consecutive phases. In the
      first stage, 150 newborns were distributed into three randomised groups, the
      first group (50 newborns) did not receive any specific analgesic intervention;
      the second and third groups (50 newborns) received non-nutritive sucking-placebo
      or non-nutritive sucking-24% sucrose respectively. In the second phase, 78
      newborns participated, and the blood was taken during breast-feeding. The results
      on a discomfort scale were compared with those obtained in the rest of examined
      analgesic procedures. RESULTS: The group that received analgesia with breast
      feeding showed a score on the discomfort scale of 0'62 and an average time of
      crying of 0'19s. The comparative analysis of the results obtained during
      breastfeeding, as opposed to the rest of procedures, showed that breast-feeding
      is the best analgesic option, with a reduction in the discomfort of 51% and of
      98% in the time of crying (P<0,001). CONCLUSIONS: Breast-feeding during the blood
      test by heel-prick procedure represents the most effective analgesic method. A
      containment procedure along with non-nutritive sucking is the analgesic method of
      choice in the newborn that does not receive maternal lactation.

PMID- 19762296
TI  - [Pediatric cerebrovascular accident secondary to fibromuscular dysplasia].
AB  - We present the case of a 13 year-old patient diagnosed with fibromuscular
      dysplasia (FMD) by angiographic study, with "string of beads" image of internal
      carotid, after undergoing two ischemic strokes in nine days. Conservative
      treatment with acetylsalicylic acid at antiaggregant doses was decided. Twenty
      months later the clinical progress is favorable without presenting any new
      episodes. FMD is a very uncommon cause of stroke in childhood. Little is known
      about its etiology. In spite of it usually being an asymptomatic disease, it must
      be considered in cases of repeated or inexplicable strokes. Its prognosis and
      treatment is controversial, due to the limited number of pediatric patients with
      this pathology.

PMID- 19762297
TI  - Identification of persons with dysglycemia: terminology and practical
      significance.
AB  - Allocating scarce resources for dysglycemia intervention requires identification
      of persons who will benefit. Identification has two steps: screening followed by
      diagnosis. Lowering a screening test's cut-off score identifies more persons with
      dysglycemia, but causes more normoglycemic persons to receive diagnostic testing.
      Raising a test's cut-off score reduces needless diagnostic testing, but increases
      the number falsely identified as not having dysglycemia. With limited budgets for
      intervention, raising a screening test's cut-off score may be appropriate. With
      ample budgets, lowering the test's cut-off score may be appropriate. Screening
      tests are most efficient in populations with high prevalence of dysglycemia.

PMID- 19762298
TI  - Incidence analyses of bladder cancer in the Nile delta region of Egypt.
AB  - Bladder cancer is the most common malignancy among Egyptian males and previously
      has been attributed to Schistosoma infection, a major risk factor for squamous
      cell carcinoma (SCC). Recently, transitional cell carcinoma (TCC) incidence has
      been increasing while SCC has declined. To investigate this shift, we analyzed
      the geographical patterns of all bladder cancers cases recorded in Egypt's
      Gharbiah Population-Based Cancer Registry from 1999 through 2002. Data on tumor
      grade, stage, and morphology, as well as smoking, community of residence, age and
      sex, were collected on 1209 bladder cancer cases. Age-adjusted incidence rates
      were calculated for males, females, and the total population for the eight
      administrative Districts and 316 communities in Gharbiah. Incidence Rate Ratios
      (IRR) and 95% confidence intervals (CI) were computed using Poisson Regression.
      The male age-adjusted incidence rate (IR) in Gharbiah Province was 13.65/100,000
      person years (PY). The District of Kotour had the highest age-adjusted IR
      28.96/100,000 among males. The District of Kotour also had the highest IRR among
      all Districts, IRR=2.15 95% CI (1.72, 2.70). Kotour's capital city had the
      highest bladder cancer incidence among the 316 communities (IR=73.11/100,000 PY).
      Future studies on sources and types of environmental pollution and exposures in
      relation to the spatial patterns of bladder cancer, particularly in Kotour
      District, may improve our understating of risk factors for bladder cancer in the
      region.

PMID- 19762299
TI  - Evaluation of the platelet function analyzer (PFA-100) vs. the thromboelastogram
      (TEG) in the clinical setting.

PMID- 19762300
TI  - Platelet function analyzer (PFA-100) offers higher sensitivity and specificity
      than thromboelastography (TEG) in detection of platelet dysfunction.
AB  - BACKGROUND: The development of advanced surgical procedures requires novel and
      early diagnostic techniques. One of the prime difficulties that need to be
      overcome is an abnormality in the coagulation system. The blood clot formation
      and fibrinolysis processes are very complicated and important perioperatively.
      However, most of the major surgeries, such as liver transplantation, use
      thromboelastography (TEG) for detection of coagulation abnormalities, even though
      TEG is not actually an ideal option. Therefore, we compared the sensitivity and
      specificity of the platelet function analyzer (PFA-100) and thromboelastogram
      (TEG) in predicting platelet dysfunction and bleeding risk. METHODS: Human blood
      samples were drawn from healthy volunteers for this study. Levobupivacaine and
      CGS21680 have antiplatelet effects which were used as the detection target. The
      platelet counts before comparison, platelet aggregation, the closure time of PFA
      100, and the parameters of TEG were examined for data analysis. RESULTS: Platelet
      aggregations were suppressed by all levobupivacaine doses (10 microg/mL, 50
      micropg/mL, 200 microg/mL) and CGS21680 (100 nM, 500 nM, 1 microM) in a dose
      dependent manner. Levobupivacaine and CGS21680 at maximal test doses produced no
      significant alteration in any parameter in the TEG assay. In the samples measured
      with PFA-100, both levobupivacaine and CGS21680 at maximal test doses
      significantly prolonged the closure time in the PFA-100 assay. CONCLUSION: We
      conclude that PFA-100 offers a higher sensitivity and specificity than TEG in
      detection of platelet dysfunction.

PMID- 19762301
TI  - Accuracy of the central landmark for catheterization of the right internal
      jugular vein after placement of the ProSeal laryngeal mask airway.
AB  - OBJECTIVE: Catheterization of the internal jugular vein (IJV) after placement of
      a laryngeal mask airway (LMA) has been reported to be difficult. The purpose of
      this study was to evaluate the accuracy of the central landmark for
      catheterization of the right IJV after placement of a ProSeal LMA. METHODS: We
      enrolled 80 patients (30 men and 50 women) who were scheduled to undergo surgery
      under general anesthesia conveyed by a size 3 ProSeal LMA. A needle pathway based
      on the central landmark for right IJV catheterization was simulated. Ultrasound
      images were obtained, which we contrasted with the simulated pathway to evaluate
      whether the landmark accuracy remained unchanged after placement of the ProSeal
      LMA. Both frequency of simulated right carotid artery (CA) puncture and overlap
      between the right IJV and right CA were also investigated. RESULTS: The simulated
      needle pathway ran along the course of the right IJV in 60% (48/80) of subjects,
      and transected the CA in 31.3% (25/80) of subjects. Both events together occurred
      in 20% (16/80) of subjects. The central landmark had a medial bias of 6.8 mm (95%
      confidence interval, 5.3-8.4). In 83.8% (67/80) of subjects, the center of the
      right IJV was lateral to the central landmark. The possibility of overlap of the
      right IJV and CA was high after ProSeal LMA placement. CONCLUSION: After
      placement of the ProSeal LMA, the central landmark could not offer a good success
      rate at the first puncture attempt. When using the central landmark to
      catheterize the IJV after a ProSeal LMA placement, medial deviation of the
      central landmark should be considered. Ultrasound guidance may be helpful in
      difficult cases.

PMID- 19762302
TI  - Closed-loop control of anesthesia using the bispectral index in open heart
      surgery.
AB  - OBJECTIVE: The introduction of the bispectral index (BIS) as a comprehensive
      indicator of depth of anesthesia has prompted research in the automated delivery
      of anesthetics. This trial aimed to evaluate the usefulness of the BIS as the
      feedback variable in a closed-loop anesthesia control system during cardiac
      surgery under cardiopulmonary bypass (CPB). METHODS: Thirty-four adult patients
      of American Society of Anesthesiologists grade I-III undergoing elective cardiac
      surgery under hypothermic CPB were evaluated prospectively in a tertiary care
      teaching hospital. The anesthesia was induced and maintained throughout surgery
      using a closed-loop anesthesia delivery system (502/DEL/2003) to control the BIS.
      RESULTS: The closed-loop system was functional during 96% of the anesthesia
      duration. The BIS was maintained at +/- 10 of the target of 50 during 86% of the
      automated anesthesia. The closed-loop system was also functional during CPB
      despite a fall in BIS probably resulting from hypothermia. None of the patients
      had recall of events or experiences during the procedure. CONCLUSION: The closed
      loop control of anesthetic delivery adjusted to BIS is feasible and may be useful
      in open heart surgery under hypothermic CPB.

PMID- 19762303
TI  - Effects of propofol sedation during the early postoperative period in hemorrhagic
      stroke patients.
AB  - BACKGROUND: The early postoperative period is a critical time for patients after
      receiving a decompressive craniotomy. Prompt detection and early management of
      postoperative recurrent/residual hemorrhagic complications may dramatically
      improve clinical outcomes. METHODS: The present cohort retrospective study
      involved 135 patients who received decompressive craniotomy and intensive care
      unit (ICU) supervision as life-saving measures. The purpose of the study was to
      evaluate the effects of propofol sedation on the clinical outcome during the ICU
      stay. The patients' demographic data, hemodynamic variables, the dose of propofol
      used during the first 48 hours after surgery, residual/recurrent blood clot
      volume after surgery, and neurologic and clinical outcomes were reviewed. The
      propofol dosages used for sedation were further divided into three categories: <
      0.66, 0.66-3.33 and > 3.33 mg/kg/hr, based on the doses infused during the first
      12 hours after surgery. RESULTS: Our results indicated that the patients of the
      propofol-sedated group had a significantly smaller amount of residual/recurrent
      blood clot (p < 0.05) than did those of the non-sedated group. The 30-day
      mortality rate was significantly lower in the propofol-sedated group (p < 0.05)
      than in the non-sedated group. Among the propofol-sedated patients, those who
      received a dose of 0.66-3.33 mg/kg/hr in the first 12 hours after surgery
      achieved significantly improved clinical and neurologic outcomes than those who
      received either more than 3.33 mg/kg/hr or less than 0.66 mg/kg/hr of propofol.
      CONCLUSION: Our results support the use of propofol sedation during the early
      postoperative period after craniotomy in hemorrhagic stroke patients, because it
      improved both neurologic and clinical outcomes. However, early postoperative use
      of propofol sedation at larger dosages warrants special attention.

PMID- 19762304
TI  - Cervicofacial subcutaneous emphysema following tonsillectomy: implications for
      anesthesiologists.
AB  - Cervicofacial subcutaneous emphysema is an unusual complication following
      tonsillectomy. We present a 37-year-old male patient who, after receiving
      tonsillectomy, developed cervicofacial subcutaneous emphysema immediately
      following endotracheal extubation. Valsalva maneuvers evidenced by coughing and
      straining of the patient, and positive pressure ventilation by mask to alleviate
      laryngospasm in an emergency were believed to induce and exacerbate the
      emphysema. Fortunately, the patient was re-intubated and protected from further
      complication of pneumomediastinum or pneumothorax. The emphysema resolved 7 days
      later with conservative treatment, including broad-spectrum antibiotics and
      abstention from enteral intake. This case serves as a reminder that an unusual
      and unexpected complication can occur in a routine procedure. Methods to prevent
      this complication are discussed.

PMID- 19762305
TI  - Fatal venous air embolism during emergence from anesthesia.
AB  - We describe a case of the sudden onset of cardiovascular collapse during
      emergence from anesthesia resulting from a massive venous air embolism, which was
      detected by transesophageal echocardiography. We present this case to remind
      anesthesiologists to be aware of the risk of a sudden return of air trapped in
      the venous system during emergence from anesthesia. The air is freed because the
      sympathetic tone is increased, muscle-pumping power is regained, ventilation
      shifts from positive-pressure to negative-pressure spontaneous ventilation, and
      the patient is repositioned after surgery.

PMID- 19762306
TI  - Anesthetic management of a patient with congenital methemoglobinemia.
AB  - Methemoglobinemia occasionally causes cyanosis particularly in congenital
      methemoglobinemia. Avoidance of exposure to oxidizing agents is important for
      patients with congenital methemoglobinemia because of their deficient enzymatic
      pathways and decreased oxygen-carrying capacity. Here, we present a patient with
      preoperatively undiagnosed congenital methemoglobinemia who underwent uterine
      myomectomy under general anesthesia. The patient was a 35-year-old woman who
      displayed a low pulse oximetry reading of 91% prior to induction of anesthesia.
      Methemoglobinemia was first suspected intraoperatively because of a mismatch of
      SpO2 of finger pulse oximetry and SaO2 of arterial blood, and was later confirmed
      by multiple-wavelength CO-oximetry. The pathophysiology, etiology, clinical
      manifestations, anesthetic considerations, and treatment options of
      methemoglobinemia are discussed.

PMID- 19762307
TI  - Acute radial nerve injury associated with an automatic blood pressure monitor.
AB  - Perioperative radial nerve injury is a rare anesthetic complication, and is
      rarely seen in association with the use of an automatic blood pressure monitor.
      As far as we know, only one case has been reported. Here, we report a 26-year-old
      healthy, lean female who sustained acute radial nerve palsy after appendectomy. A
      dropped wrist improved 5 days later. The cause of the radial neuropathy is
      discussed. We recommend that when an automatically cycling blood pressure monitor
      is used on a lean patient, caution should be taken against such a complication.

PMID- 19762308
TI  - Complete atrioventricular block with bradycardia after craniotomy.
AB  - We report an 82-year-old male patient who developed complete atrioventricular
      block (CAVB) with severe bradycardia 1 hour after craniotomy. After emergency
      placement of a transvenous pacemaker, the patient's heart rate was restored.
      Serial assays of serum cardiac enzymes, echocardiography and serum digoxin
      concentration did not show evidence of myocardial infarction, myocardial injury,
      or drug toxicity. Tracing back past history, neither syncope nor arrhythmia of
      any form was noted. A neurogenic heart disorder, high vagal tone, and aging
      possibly contributed to this cardiac event in this patient. CAVB, although
      uncommon, is a disastrous complication following craniotomy, and needs aggressive
      and instantaneous management.

PMID- 19762309
TI  - Rapid sequence intubation using Pentax-AWS without muscle relaxants in patients
      with myasthenia gravis.

PMID- 19762310
TI  - Sub-tenon block and laryngeal mask for anesthesia in a child with isolated
      pulmonary stenosis undergoing squint surgery.

PMID- 19762311
TI  - Osteosarcoma: is age an issue?

PMID- 19762312
TI  - Osteosarcoma in preadolescent patients: experience in a single institute in
      Taiwan.
AB  - BACKGROUND: The incidence of osteosarcoma peaks in adolescence and is much lower
      in preadolescence. However, reports on its clinical features in preadolescent
      patients are conflicting. In this study, we attempted to assess the differences
      in clinical appearance and prognosis of the malignancy between preadolescent and
      adolescent patients. METHODS: Between January 1980 and January 2006, 13
      preadolescent and 58 adolescent patients with high-grade osteosarcoma were
      treated at our institute, and their medical records were reviewed and compared.
      RESULTS: The sex distribution, primary metastasis rate, pathologic fracture,
      histologic type, primary tumor location, and percentage of high alkaline
      phosphatase level were not different between the 2 groups. Poor responders (tumor
      necrosis rate < 90%) were more common in the preadolescent group (80% vs. 43%, p
      = 0.035). Overall survival rates in the preadolescent and adolescent groups were
      51.3% and 56.4%, respectively (p = 0.735). In patients without primary
      metastasis, the 5-year overall survival rates were 60.6% and 66.7% for 11
      preadolescents and 39 adolescents, respectively (p = 0.925). CONCLUSION:
      Considering the common findings in both groups, we suggest that preadolescent
      patients should be treated with the same regimen as that used for adolescent
      patients.

PMID- 19762313
TI  - Growth hormone therapy in neonatal patients with methylmalonic acidemia.
AB  - BACKGROUND: Information regarding growth hormone (GH) therapy in neonatal
      patients with methylmalonic academia (MMA) is lacking. We present our experience
      with GH therapy in neonatal patients with MMA. METHODS: Four neonatal patients
      with mut 0 type MMA were identified through newborn screening for elevated
      propionylcarnitine (C3) levels. GH therapy (0.6 IU/kg/week, subcutaneously) was
      prescribed for patient 1 after 1 month of admission, and was prescribed for
      patients 2, 3 and 4 on the 1st day of admission. We evaluated weight, skin
      erosion, hospital stay, and serum levels of C3 after GH therapy. RESULTS: All of
      the neonatal patients with MMA displayed obvious weight gain and distinct
      improvement in skin erosions after GH therapy. The duration of hospital stay for
      patients 2, 3 and 4 was reduced compared to that of patient 1. However, the
      metabolic effects of GH therapy on reducing serum levels of C3 seem to be
      indeterminate. CONCLUSION: Our clinical findings suggest that GH therapy has
      potentially beneficial effects on neonatal patients with MMA.

PMID- 19762314
TI  - Airway management of patients with craniofacial abnormalities: 10-year experience
      at a teaching hospital in Taiwan.
AB  - BACKGROUND: Airway management for patients with craniofacial abnormalities poses
      many challenges. It potentially has a high rate of morbidity and even mortality.
      METHODS: We reviewed our experience in administering anesthesia to patients with
      a diagnosis of mucopolysaccharidosis or Pierre Robin sequence in the past 10
      years (July 1998 to October 2008). The anesthetic procedures, methods of airway
      management, and events of morbidity and mortality were evaluated. RESULTS: Thirty
      patients with mucopolysaccharidosis and 53 patients with Pierre Robin sequence
      were placed under general anesthesia. Although the anesthesiologists always
      encountered difficulties in managing the airway, most of the anesthetic
      procedures were performed safely except for 1 case that resulted in mortality.
      CONCLUSION: Managing the airway of patients with craniofacial abnormalities can
      potentially be difficult. It should be carried out by experienced
      anesthesiologists, with assistance from an otolaryngologist when necessary. A
      variety of different airway devices should be available if needed.

PMID- 19762315
TI  - Sex distribution and psychiatric features of child and adolescent conversion
      disorder across 2 decades.
AB  - BACKGROUND: Earlier research suggested female predominance in adult conversion
      disorder, and the strong association between conversion disorder and experiences
      of being abused is well known. However, the data for child and adolescent
      populations are limited. In Taiwan, the dramatic increase in child abuse may have
      some impact on the features of child and adolescent conversion disorder. This
      study aimed to compare the demographic characteristics, psychiatric comorbidity,
      and experiences of being abused in Taiwanese children and adolescents diagnosed
      with conversion disorder in psychiatric consultations across 2 decades. METHODS:
      Retrospective and consecutive chart reviews were conducted for child and
      adolescent patients (< 20 years old) who were newly diagnosed with conversion
      disorder in psychiatric consultations at Taipei Veterans General Hospital from
      1987 to 2006. The first group included patients who were diagnosed between 1987
      and 1996 (the first decade), and the second group included patients who were
      diagnosed between 1997 and 2006 (the second decade). RESULTS: A total of 42
      patients diagnosed with conversion disorder were included in this study. Nineteen
      of the 42 subjects were diagnosed in the first decade (from 1987 to 1996), and 23
      in the second decade (from 1997 to 2006). There existed among patients a tendency
      toward an increasing number of male subjects (p < 0.05), suffering more abuse (p
      < 0.05), and higher prevalence rates of depression and dysthymia comorbidity (p <
      0.05) in the second decade compared to the first. CONCLUSION: The sex
      distribution in conversion disorder might have significantly changed over the
      past 2 decades. There is an increasing need for screening and interventions for
      psychiatric comorbidity and experiences of being abused in children and
      adolescents with conversion disorder. Because of the small sample size of our
      study, further studies that include multiple study sites and a larger number of
      patients are needed before a firm conclusion can be drawn.

PMID- 19762316
TI  - Depression is the strongest independent risk factor for poor social engagement
      among Chinese elderly veteran assisted-living residents.
AB  - BACKGROUND: Social engagement prolongs the lifespan and preserves cognition in
      the elderly. However, most studies concerning social engagement have been
      conducted in Western countries; few have been performed in the Chinese
      population. This study attempted to identify the risk factors for poor social
      engagement among elderly veterans in Taiwan. METHODS: A total of 597 male
      veterans were enrolled, with a mean age of 80.8 +/- 5.0 years. This cross
      sectional study employed the Resident Assessment Instrument (RAI) Minimum Data
      Set (MDS), the Geriatric Depression Scale-Short Form (GDS-SF), and the Mini
      Mental State Examination (MMSE). Multivariate logistic regression analysis was
      done to investigate significant independent risk factors for poor social
      engagement, which were identified using the MDS Index of Social Engagement (ISE).
      RESULTS: Mean ISE score was 1.5 +/- 1.3 (range, 0-5); 52% of subjects had poor
      levels of social engagement (ISE < 2; 312/597). Regression analyses suggested
      that depression (OR, 6.6; 95% CI, 2.7-16.1; p < 0.001), illiteracy (OR, 2.2; 95%
      CI, 1.3-3.8; p = 0.003), the presence of unsettled relationships (OR, 3.6; 95%
      CI, 1.5-8.7; p = 0.004), and cognitive impairment (OR, 2.0; 95% CI, 1.1-3.9; p =
      0.03) were significant independent risk factors for poor social engagement, after
      controlling for age, marital status, level of daily living activity and degree of
      sensory impairment. CONCLUSION: Poor social engagement is common among Chinese
      assisted-living veteran home residents. Depression is the greatest risk factor of
      poor social engagement in this population.

PMID- 19762317
TI  - Hemorrhagic acalculous cholecystitis: an unusual location of uremic bleeding.
AB  - Hemorrhagic acalculous cholecystitis is a rare but potentially fatal disease. An
      increased bleeding tendency is present in both acute and chronic renal failure
      with impaired platelet function. We herein present a case of hemorrhagic
      acalculous cholecystitis in a hemodialysis patient who suffered from acute
      abdomen and upper gastrointestinal bleeding. The pathogenesis may have been
      associated with ischemia and reperfusion injury, eventually leading to necrosis
      of the gallbladder wall. Abdominal ultrasound can aid in diagnosis. Biliary
      colic, jaundice, and melena are the typical symptoms of hemorrhagic
      cholecystitis, particularly in a patient with unexplained gastrointestinal
      bleeding.

PMID- 19762318
TI  - Bilateral tension pneumothorax and tension pneumoperitoneum secondary to tracheal
      tear in a patient with relapsing polychondritis.
AB  - Relapsing polychondritis (RP) is a rare disease that is characterized by
      recurrent inflammation and destruction of cartilage and connective tissues. RP
      can have significant airway pathology that may require procedures to maintain
      airway patency and thus may have serious implications for anesthesiologists.
      Anesthesiologists must be prepared to deal with the possible complications that
      may occur during airway manipulation in patients with RP. Here, we present a case
      of life-threatening bilateral tension pneumothorax and tension pneumoperitoneum
      that developed after a tracheal tear during Montgomery T-tube insertion in a
      patient with tracheal stenosis due to RP. Correct diagnosis was delayed due to a
      misdiagnosis of airway obstruction. As a result, we emphasize that bilateral
      tension pneumothorax should be considered during refractory cardiac arrest in
      patients with increased airway pressure. A high index of suspicion and adequate
      management are mandatory for patients to survive these life-threatening
      complications.

PMID- 19762319
TI  - Fibromatosis of the submandibular region.
AB  - Fibromatoses are benign tumors that can occur anywhere in the body. They are
      locally aggressive and tend to recur; they also cause considerable morbidity,
      particularly when they arise in the head and neck. Fibromatosis in the
      submandibular region is rare. Here, we present a case of fibromatosis of the
      submandibular region in a 42-year-old female who presented with a right
      submandibular mass. The patient underwent complete excision of the fibromatosis,
      showed negative margins and had no adjuvant therapy. Her recovery was uneventful,
      and there was no recurrence or neurological deficit 1 year after the operation.

PMID- 19762320
TI  - Osteoclast-like giant cell carcinoma of the urinary bladder.
AB  - Extraskeletal osteoclast-like giant cell (OGC) tumors are uncommon and have
      mainly been found in the breast and pancreas. OGC neoplasms of the urinary tract
      are extremely rare, and their histogenesis and biologic behavior remain
      controversial. Gross hematuria is the most common presenting symptom, as in
      transitional cell carcinoma. The prognosis is poor in patients with extraskeletal
      OGC tumors. Here, we present the case of a 62-year-old man who received
      transurethral bladder tumor resection due to painless gross hematuria. Pathology
      showed OGC carcinoma. Abdominal computed tomography showed tumor invasion over
      the right lateral wall of the bladder and distal third of the ureter. The patient
      received radical cystectomy and partial distal ureterectomy with
      transureteroureterostomy. No local tumor recurrence or distant metastasis was
      found at the 5-month follow-up.

PMID- 19762321
TI  - Spontaneous esophageal injury: esophageal intramural hematoma.
AB  - Acute chest pain can indicate a life-threatening condition and it is important
      for physicians to diagnose and treat it as a matter of urgency. We report 1 rare
      case of esophageal intramural hematoma (IMH) that presented with chest pain at
      the emergency department and which was initially clinically suspected to be due
      to aortic dissection. The case was diagnosed preoperatively by multidetector
      computed tomography. Esophageal IMH may represent an intermediate stage between
      Mallory-Weiss tear (mucosal) and Boerhaave's syndrome (transmural). Multidetector
      computed tomography is a useful noninvasive imaging modality for accurate
      diagnosis of these spontaneous intramural and transmural ruptures of the
      esophagus, and aids in the differential diagnosis of aortic and other mediastinal
      diseases with acute chest pain.

PMID- 19762322
TI  - Photodynamic therapy in the treatment of choroidal neovascularization
      complicating central serous chorioretinopathy.
AB  - We report the favorable anatomic and functional outcome of photodynamic therapy
      with verteporfin in a case of chronic central serous chorioretinopathy
      complicated with choroidal neovascularization (CNV). This 37-year-old Chinese
      male with bilateral chronic central serous chorioretinopathy presented with
      central scotoma, reduced vision and metamorphopsia in his right eye. Fluorescein
      angiography (FA) disclosed macular hemorrhage, exudate and subfoveal classic CNV.
      Photodynamic therapy (PDT) with verteporfin was applied to the CNV according to
      standard protocol with 2.2-mm spot size. Best-corrected visual acuity (BCVA)
      improved from 6/20 to 6/10 1 month after PDT. BCVA recovered to 6/7.5 without
      leakage on FA 3 months after PDT. Neither recurrent CNV lesion nor new hemorrhage
      was noted over 12 months of follow-up. Short-term results suggest that PDT with
      verteporfin for CNV secondary to central serous chorioretinopathy is a safe and
      effective treatment modality.

PMID- 19762323
TI  - [Hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC): evaluation,
      prevention and policies to avoid occupational exposure for operating room
      personnel].
AB  - To develop a treatment strategy for peritoneal carcinomatosis using a combination
      of extended peritoneal resections, local destructive procedures and hyperthermic
      intraperitoneal chemotherapy creates great concern between healthcare workers
      involved in these procedures. New professional risks exist: risk of exposure to
      cytotoxic drugs, environmental risks (inhalation of smoke, aerosolization of
      chemotherapy agents). Information, education and training of healthcare workers
      is mandatory in order to ensure proper evaluation, prevention, and management of
      professional exposure risks in coordination with the occupational health office.

PMID- 19762324
TI  - [Access to preventative care, screening and treatment of women in vulnerable
      socio-economic groups presenting with cervical cancer].
AB  - AIM: The object of this study was to evaluate access to preventative care,
      screening and treatment of women in vulnerable socio-economic groups presenting
      with cervical cancer and the progression of their disease. METHOD: This is a
      retrospective study of 123 patients with cervical cancer treated at the hopital
      Bichat (Paris) or the hopital Verdier (Bondy) between 1st January 1996 and 31
      December 2005. RESULTS: "CMU" or "AME" is the entitlement for fully state funded
      medical care and was used in this study to indicate social deprivation. Social
      deprivation is associated with homelessness (43.9 vs 1.23%; P = 0.0001) and
      unemployment (90 vs 30%; P = 0.0001). Women from deprived groups seldom enter
      screening programs (25 vs 56.1%; P = 0.008). Once symptomatic they delay seeking
      medical attention (1.8 months later than for non-deprived groups; P = 0.027),
      present more often to accident and emergency departments (51.22 vs 17.07%; P =
      0.0003), and do not see any primary care practitioner (41.46 vs 8.64%; P <
      0.0001). There was no significant difference with regard to treatment instituted
      in the two groups. The non-deprived patients residing in Bondy had similar access
      to care as the deprived patients treated in Paris. The average follow-up period
      was 30.43 months (+/- 26.64). CONCLUSION: Cervical screening is not taken up
      adequately throughout the general population. Access to health care is poorly
      tailored to the needs of the socially deprived. Social deprivation did not
      demonstrate an association with levels of pelvic recurrence, metastasis or death.
      The low doctor to patient ratio in certain geographical areas reduces access to
      medical care.

PMID- 19762325
TI  - XRCC1 codon 280 and ERCC2 codon 751 polymorphisms and risk of esophageal squamous
      cell carcinoma in a Chinese population.
AB  - Numerous candidate genes have been proposed as susceptibility factors for the
      development of esophageal squamous cell carcinoma (ESCC). XRCC1 (X-ray cross
      complementing group 1) codon 280 and ERCC2 (excision repair cross complementing
      group 2) codon 751 polymorphisms were studied in ESCC in a Chinese population.
      The aim of this study is to investigate the potential association between single
      nucleotide polymorphisms (SNP) of XRCC1 codon 280 His and ERCC2 codon 751 Gln
      polymorphisms and ESCC. Peripheral blood samples of 200 cases and 200 age-and
      gender matching controls were collected from a Chinese population and the two
      polymorphisms were studied by means of polymerase chain reaction (PCR)
      restriction fragment length polymorphism techniques. Our results showed that
      XRCC1 codon 280 His allele had no significant difference between ESCC patients
      and normal controls (P > 0.05), while ERCC2 codon 751Gln allele was associated
      with a borderline decrease of ESCC (odds ratio [OR] = 0.628, 95% confidence
      interval [CI]: 0.400-0.986).

PMID- 19762326
TI  - An electrophysiological approach to the diagnosis of neurogenic dysphagia:
      implications for botulinum toxin treatment.
AB  - OBJECTIVES: Botulinum toxin (BTX) injection into the cricopharyngeal (CP) muscle
      has been proposed for the treatment of neurogenic dysphagia due to CP
      hyperactivity. The aim was to determine whether an electrophysiological method
      exploring oropharyngeal swallowing could guide treatment and discriminate
      responders from non-responders, based on the association of CP dysfunction with
      other electrophysiological abnormalities of swallowing. METHODS: Patients with
      different neurological disorders were examined: Parkinson disease, progressive
      supranuclear palsy, multiple system atrophy-Parkinson variant, multiple system
      atrophy cerebellar variant, stroke, multiple sclerosis and ataxia telangiectasia.
      All patients presented with clinical dysphagia, and with complete absence of CP
      muscle inhibition during the hypopharyngeal phase of swallowing. Each patient
      underwent clinical and electrophysiological investigations before and after
      treatment with BTX into the CP muscle of one side (15 units of Botox). Clinical
      and electrophysiological procedures were performed in a blind manner by two
      different investigators. The following electrophysiological measures were
      analysed: (1) duration of EMG activity of suprahyoid/submental muscles (SHEMG-D);
      (2) duration of laryngopharyngeal mechanogram (LPM-D); (3) duration of the
      inhibition of the CP muscle EMG activity (CPEMG-ID); and (4) interval between
      onset of EMG activity of suprahyoid/submental muscles and onset of
      laryngopharyngeal mechanogram (I-SHEMG-LPM). RESULTS: Two months after treatment,
      50% of patients showed a significant improvement. Patients with prolonged or
      reduced SHEMG-D values and prolonged I-SHEMG-LPM values did not respond to BTX.
      Therefore, values for which BTX had no effect (warning values) were identified.
      CONCLUSIONS: This electrophysiological method can recognise swallowing
      abnormalities which may affect the outcome of the therapeutic approach to
      dysphagia with BTX treatment.

PMID- 19762327
TI  - Impaired recruitment of HHT-1 mononuclear cells to the ischaemic heart is due to
      an altered CXCR4/CD26 balance.
AB  - AIMS: Mononuclear cells (MNCs) from patients with hereditary haemorrhagic
      telangiectasia type 1 (HHT1), a genetic disorder caused by mutations in endoglin,
      show a reduced ability to home to infarcted mouse myocardium. Stromal cell
      derived factor-1alpha (SDF-1alpha) and the chemokine receptor CXCR4 are crucial
      for homing and negatively influenced by CD26. The aim of this study was to gain
      insight into the impaired homing of HHT1-MNCs. METHODS AND RESULTS: CXCR4 and
      CD26 expression on MNCs was determined by flow cytometry. Transwell migration to
      SDF-1alpha was used to analyse in vitro migration. Experimentally induced
      myocardial infarction in mice, followed by tail vein injection of MNCs, was
      applied to study homing in vivo. HHT1-MNCs expressed elevated levels of CXCR4,
      but this was counterbalanced by high levels of CD26, resulting in decreased
      migration towards an SDF-1alpha gradient in vitro. Migration was enhanced by
      inhibiting CD26 with Diprotin-A. While MNCs from healthy controls responded to
      transforming growth factor-beta stimulation by increasing CXCR4 and lowering CD26
      expression levels, HHT1-MNCs did not react as efficiently: in particular, CD26
      expression remained high. Inhibiting CD26 on MNCs increased the homing of human
      cells into the infarcted mouse heart. Interestingly, the defect in homing of HHT1
      MNCs was restored by pre-incubating the HHT1-MNCs with Diprotin-A before
      injection into the tail vein. CONCLUSION: We show that a decreased homing of HHT1
      MNCs is caused by an impaired ability of the cells to respond to SDF-1alpha. Our
      results suggest that modulating CD26 levels using inhibitors like Diprotin-A can
      restore homing in cases where increased expression of CD26 contributes to the
      underlying pathological mechanism.

PMID- 19762329
TI  - Submicroscopic chromosomal imbalances in idiopathic Silver-Russell syndrome
      (SRS): the SRS phenotype overlaps with the 12q14 microdeletion syndrome.
AB  - Silver-Russell syndrome (SRS) is a heterogeneous disorder associated with
      intrauterine and postnatal growth restriction, body asymmetry, a relative
      macrocephaly, a characteristic triangular face and further dysmorphisms. In about
      50% of patients, genetic/epigenetic alterations can be detected: >38% of patients
      show a hypomethylation of the IGF2/H19 imprinting region in 11p15, whereas the
      additional 10% carry a maternal uniparental disomy of chromosome 7. In single
      cases, cytogenetic aberrations can be detected. Nevertheless, there still remain
      50% of SRS patients without known genetic/epigenetic alterations. To find out
      whether submicroscopic imbalances contribute to the aetiology of SRS, 20
      idiopathic SRS patients were screened with the Affymetrix GeneChip Human Mapping
      500 K array set. Apart from known apathogenic copy number variations, we
      identified one patient with a 12q14 microdeletion. The 12q14 microdeletion
      syndrome is characterised by dwarfism but it additionally includes mental
      retardation and osteopoikilosis. The deletion in our patient is smaller than
      those in the 12q14 microdeletion carriers but it also affects the LEMD3 and the
      HMGA2 genes. LEMD3 haploinsufficiency and point mutations have been previously
      associated with osteopoikilosis but radiographs of our patient at the age of 16
      years did not reveal any hint for osteopoikilosis lesions. Haploinsufficiency of
      HMGA2 is probably responsible for aberrant growth in 12q14 microdeletion
      syndrome. However, in this study, a general role of HMGA2 mutations for SRS was
      excluded by sequencing of 20 idiopathic patients. In conclusion, our results
      exclude a common cryptic chromosomal imbalance in idiopathic SRS patients but
      show that chromosomal aberrations are relevant in this disease. Thus, molecular
      karyotyping is indicated in SRS and should be included in the diagnostic
      algorithm.

PMID- 19762330
TI  - A life-threatening arrhythmia induced by inappropriate activation of an
      implantable cardioverter defibrillator.
AB  - We describe an unusual case of near fatal inappropriate implantable cardioverter
      defibrillator therapies due to atrial oversensing by a newly implanted
      ventricular lead. Chest X-ray revealed dislodgement of the active fixation lead
      to the tricuspid annulus area explaining the atrial oversensing and intermittent
      ventricular therapies.

PMID- 19762328
TI  - A gain-of-function TBX20 mutation causes congenital atrial septal defects, patent
      foramen ovale and cardiac valve defects.
AB  - BACKGROUND: Ostium secundum atrial septal defects (ASDII) account for
      approximately 10% of all congenital heart defects (CHD), and mutations in cardiac
      transcription factors, including TBX20, were identified as an underlying cause
      for ASDII. However, very little is known about disease penetrance in families and
      functional consequences of inherited TBX20 mutations. METHODS: The coding region
      of TBX20 was directly sequenced in 170 ASDII patients. Functional consequences of
      one novel mutation were investigated by surface plasmon resonance, CD
      spectropolarymetry, fluorescence spectrophotometry, luciferase assay and
      chromatin immunoprecipitation. RESULTS: We found a novel mutation in a highly
      conserved residue in the T-box DNA binding domain (I121M) segregating with CHD in
      a three generation kindred. Four mutation carriers revealed cardiac phenotypes in
      terms of cribriform ASDII, large patent foramen ovale or cardiac valve defects.
      Interestingly, tertiary hydrophobic interactions within the mutant TBX20 T-box
      were significantly altered leading to a more dynamic structure of the protein.
      Moreover, Tbx20-I121M resulted in a significantly enhanced transcriptional
      activity, which was further increased in the presence of co-transcription factors
      GATA4/5 and NKX2-5. Occupancy of DNA binding sites on target genes was also
      increased. CONCLUSIONS: We suggest that TBX20-I121M adopts a more fluid tertiary
      structure leading to enhanced interactions with cofactors and more stable
      transcriptional complexes on target DNA sequences. Our data, combined with that
      of others, suggest that human ASDII may be related to loss-of-function as well as
      gain-of-function TBX20 mutations.

PMID- 19762331
TI  - Transition of orthodromic tachycardia into atrioventricular nodal tachycardia
      during radiofrequency ablation of an accessory pathway.
AB  - We report a patient with Wolff-Parkinson-White syndrome, in whom orthodromic
      atrioventricular reciprocating tachycardia directly passed over to
      atrioventricular nodal re-entrant tachycardia during radiofrequency ablation of
      the accessory pathway. After the accessory pathway ablation, there were no
      tachycardia recurrences.

PMID- 19762332
TI  - Difference in percentage of ventricular pacing between two algorithms for
      minimizing ventricular pacing: results of the IDEAL RVP (Identify the Best
      Algorithm for Reducing Unnecessary Right Ventricular Pacing) study.
AB  - AIMS: Managed ventricular pacing (MVP) and Search AV+ are representative dual
      chamber pacing algorithms for minimizing ventricular pacing (VP). This
      randomized, crossover study aimed to examine the difference in ability to reduce
      percentage of VP (%VP) between these two algorithms. METHODS AND RESULTS:
      Symptomatic bradyarrhythmia patients implanted with a pacemaker equipped with
      both algorithms (Adapta DR, Medtronic) were enrolled. The %VPs of the patients
      during two periods were compared: 1 month operation of either one of the two
      algorithms for each period. All patients were categorized into subgroups
      according to the atrioventricular block (AVB) status at baseline: no AVB (nAVB),
      first-degree AVB (1AVB), second-degree AVB (2AVB), episodic third-degree AVB
      (e3AVB), and persistent third-degree AVB (p3AVB). Data were available from 127
      patients for the analysis. For all patient subgroups, except for p3AVB category,
      the median %VPs were lower during the MVP operation than those during the Search
      AV+ (nAVB: 0.2 vs. 0.8%, P < 0.0001; 1AVB: 2.3 vs. 27.4%, P = 0.001; 2AVB: 16.4%
      vs. 91.9%, P = 0.0052; e3AVB: 37.7% vs. 92.7%, P = 0.0003). CONCLUSION: Managed
      ventricular pacing algorithm, when compared with Search AV+, offers further %VP
      reduction in patients implanted with a dual-chamber pacemaker, except for
      patients diagnosed with persistent loss of atrioventricular conduction.

PMID- 19762333
TI  - Chromosomal and genetic alterations in human hepatocellular adenomas associated
      with type Ia glycogen storage disease.
AB  - Hepatocellular adenoma (HCA) is a frequent long-term complication of glycogen
      storage disease type I (GSD I) and malignant transformation to hepatocellular
      carcinoma (HCC) is known to occur in some cases. However, the molecular
      pathogenesis of tumor development in GSD I is unclear. This study was conducted
      to systematically investigate chromosomal and genetic alterations in HCA
      associated with GSD I. Genome-wide SNP analysis and mutation detection of target
      genes was performed in ten GSD Ia-associated HCA and seven general population HCA
      cases for comparison. Chromosomal aberrations were detected in 60% of the GSD Ia
      HCA and 57% of general population HCA. Intriguingly, simultaneous gain of
      chromosome 6p and loss of 6q were only seen in GSD Ia HCA (three cases) with one
      additional GSD I patient showing submicroscopic 6q14.1 deletion. The sizes of GSD
      Ia adenomas with chromosome 6 aberrations were larger than the sizes of adenomas
      without the changes (P = 0.012). Expression of IGF2R and LATS1 candidate tumor
      suppressor genes at 6q was reduced in more than 50% of GSD Ia HCA that were
      examined (n = 7). None of the GSD Ia HCA had biallelic mutations in the HNF1A
      gene. These findings give the first insight into the distinct genomic and genetic
      characteristics of HCA associated with GSD Ia. These results strongly suggest
      that chromosome 6 alterations could be an early event in the liver tumorigenesis
      in GSD I, and may be in general population. These results also suggest an
      interesting relationship between GSD Ia HCA and steps to HCC transformation.

PMID- 19762334
TI  - A time line of the environmental genetics of the haptophytes.
AB  - The use of genomic data and the rise of phylogenomics have radically changed our
      view of the eukaryotic tree of life at a high taxonomic level by identifying 4-6
      "supergroups." Yet, our understanding of the evolution of key innovations within
      each of these supergroups is limited because of poor species sampling relative to
      the massive diversity encompassed by each supergroup. Here we apply a multigene
      approach that incorporates a wide taxonomic diversity to infer the time line of
      the emergence of strategic evolutionary transitions in the haptophytes, a group
      of ecologically and biogeochemically significant marine protists that belong to
      the Chromalveolata supergroup. Four genes (SSU, LSU, tufA, and rbcL) were
      extensively analyzed under several Bayesian models to assess the robustness of
      the phylogeny, particularly with respect to 1) data partitioning; 2) the origin
      of the genes (host vs. endosymbiont); 3) across-site rate variation; and 4)
      across-lineage rate variation. We show with a relaxed clock analysis that the
      origin of haptophytes dates back to 824 million years ago (Ma) (95% highest
      probability density 1,031-637 Ma). Our dating results show that the ability to
      calcify evolved earlier than previously thought, between 329 and 291 Ma, in the
      Carboniferous period and that the transition from mixotrophy to autotrophy
      occurred during the same time period. Although these two transitions precede a
      habitat change of major diversities from coastal/neritic waters to the pelagic
      realm (291-243 Ma, around the Permian/Triassic boundary event), the emergence of
      calcification, full autotrophy, and oceanic lifestyle seem mutually independent.

PMID- 19762335
TI  - Guggulsterone enhances head and neck cancer therapies via inhibition of signal
      transducer and activator of transcription-3.
AB  - Treatment of human head and neck squamous cell carcinoma (HNSCC) cell lines with
      guggulsterone, a widely available, well-tolerated nutraceutical, demonstrated
      dose-dependent decreases in cell viability with EC(50)s ranging from 5 to 8
      microM. Guggulsterone induced apoptosis and cell cycle arrest, inhibited invasion
      and enhanced the efficacy of erlotinib, cetuximab and cisplatin in HNSCC cell
      lines. Guggulsterone induced decreased expression of both phosphotyrosine and
      total signal transducer and activator of transcription (STAT)-3, which
      contributed to guggulsterone's growth inhibitory effect. Hypoxia-inducible factor
      (HIF)-1alpha was also decreased in response to guggulsterone treatment. In a
      xenograft model of HNSCC, guggulsterone treatment resulted in increased apoptosis
      and decreased expression of STAT3. In vivo treatment with a guggulsterone
      containing natural product, Guggulipid, resulted in decreased rates of tumor
      growth and enhancement of cetuximab's activity. Our results suggest that
      guggulsterone-mediated inhibition of STAT3 and HIF-1alpha provide a biologic
      rationale for further clinical investigation of this compound in the treatment of
      HNSCC.

PMID- 19762336
TI  - A polymorphic variant in human MDM4 associates with accelerated age of onset of
      estrogen receptor negative breast cancer.
AB  - Murine double minute 4 (MDM4) shares significant structural homology with murine
      double minute 2 (MDM2) and interacts and regulates transcriptional activity of
      the tumor suppressor p53. In tumors with wild-type p53, there is often
      overexpression of MDM2 or MDM4 leading to functional inactivation of p53. A
      single-nucleotide polymorphism (SNP) in the promoter of human MDM2 (SNP309) was
      shown to associate with increased MDM2 expression and increased risk of cancer.
      This study evaluated the association of a SNP in human MDM4 (C>T) with age of
      onset of breast cancer in two independent cohorts. In cohort 1 of 675 patients,
      the average age of diagnosis for women with estrogen receptor (ER)-positive and
      ER-negative breast cancers was 53.2 and 48 years, respectively. In this cohort,
      homozygous variant (TT) carriers developed ER-negative carcinomas at an earlier
      age than homozygous wild-type (CC) or heterozygous (TC) such that the age at
      diagnosis was accelerated by 5.0 years (P = 0.018). This association was
      validated in a second cohort of breast cancer patients (n = 148), where TT
      carriers with ER-negative cancer developed the disease 3.8 years earlier than CC
      carriers (P = 0.006). The effect was more pronounced in Caucasians with ER
      negative ductal carcinomas with TT homozygotes developing disease 7.5 years (P =
      0.031) and 6.2 years (P = 7 x 10(-5)) earlier than CC carriers in cohorts 1 and
      2, respectively. No association was seen in ER-positive ductal cancers suggesting
      that the SNP in MDM4 only has a functional association in ER-negative breast
      cancer.

PMID- 19762337
TI  - New dynamics in an old friend: dynamic tubular vacuoles radiate through the
      cortical cytoplasm of red onion epidermal cells.
AB  - The textbook image of the plant vacuole sitting passively in the centre of the
      cell is not always correct. We observed vacuole dynamics in the epidermal cells
      of red onion (Allium cepa) bulbs, using confocal microscopy to detect
      autofluorescence from the pigment anthocyanin. The central vacuole was penetrated
      by highly mobile transvacuolar strands of cytoplasm, which were also visible in
      concurrent transmitted light images. Tubular vacuoles also extended from the
      large central vacuole and radiated through the cortical cytoplasm. These tubules
      were thin, having a diameter of about 1.5 microm, and were connected to the
      central vacuole as shown by fluorescence recovery after photobleaching (FRAP)
      experiments. The tubules were bounded by the tonoplast, as revealed by transient
      expression of green fluorescent protein (GFP) targeted to the vacuolar membrane
      and through labeling with the dye MDY-64. Expression of endoplasmic reticulum
      targeted GFP demonstrated that the vacuolar tubules were distinct from the
      cortical endoplasmic reticulum. Movement of the tubular vacuoles depended on
      actin microfilaments, as microfilament disruption blocked tubule movement and
      caused their collapse into minivacuoles. The close association of the tubules
      with GFP-tagged actin microfilaments suggests that the tubules are associated
      with myosin, and that tubules likely move along microfilaments. Tubular vacuoles
      do not require anthocyanin for their formation, as tubules were also present in
      white onion cells that lack anthocyanin. The function of these tubular vacuoles
      remains unknown, but as they greatly increase the surface area of the tonoplast,
      they might increase transport rates between the cytoplasm and vacuole.

PMID- 19762338
TI  - Stability in community-acquired pneumonia: one step forward with markers?
AB  - BACKGROUND: Biological markers as an expression of systemic inflammation have
      been recognised as useful for evaluating the host response in community-acquired
      pneumonia (CAP). The objective of this study was to evaluate whether the
      biological markers procalcitonin (PCT) and C-reactive protein (CRP) might reflect
      stability after 72 h of treatment and the absence of subsequent severe
      complications. METHODS: A prospective cohort study was performed in 394
      hospitalised patients with CAP. Clinical stability was evaluated using modified
      Halm's criteria: temperature <or=37.2 degrees C; heart rate <or=100 beats/min;
      respiratory rate <or=24 breaths/min; systolic blood pressure >or=90 mm Hg; oxygen
      saturation >or=90%; or arterial oxygen tension >or=60 mm Hg. PCT and CRP levels
      were measured on day 1 and after 72 h. Severe complications were defined as
      mechanical ventilation, shock and/or intensive care unit (ICU) admission, or
      death after 72 h of treatment. RESULTS: 220 patients achieved clinical stability
      at 72 h and had significantly lower levels of CRP (4.2 vs 7 mg/dl) and of PCT
      (0.33 vs 0.48 ng/ml). Regression logistic analyses were performed to calculate
      several areas under the ROC curve (AUC) to predict severe complications. The AUC
      for clinical stability was 0.77, 0.84 when CRP was added (p = 0.059) and 0.77
      when PCT was added (p = 0.45). When clinical stability was achieved within 72 h
      and marker levels were below the cut-off points (0.25 ng/ml for PCT and 3 mg/dl
      for CRP), no severe complications occurred. CONCLUSIONS: Low levels of CRP and
      PCT at 72 h in addition to clinical criteria might improve the prediction of
      absence of severe complications.

PMID- 19762339
TI  - Antisense transcription occurs at the promoter of a mouse imprinted gene, commd1,
      on the repressed paternal allele.
AB  - The Commd1 gene is imprinted in the adult mouse brain and is predominantly
      expressed from the maternal allele. A paternally expressing imprinted gene, U2af1
      rs1, resides in the first intron of Commd1 in an antisense orientation. We found
      that RNA polymerase II phosphorylated at serine 2 of the carboxyl-terminal domain
      repeats, a marker of transcription elongation, is enriched on the paternal allele
      than on the maternal allele in the Commd1 promoter. The Commd1 promoter harbours
      no allelic differences in DNA methylation and histone modifications. These
      results strongly suggested that imprinting of Commd1 is generated by interference
      with paternal Commd1 transcription by the oppositely directed U2af1-rs1
      transcription.

PMID- 19762340
TI  - Role of Nrf2 and p62/ZIP in the neurite outgrowth by carnosic acid in PC12h
      cells.
AB  - Neurotrophins such as NGF promote neuronal survival and differentiation via the
      cell surface TrkA neurotrophin receptor. Compounds with neurotrophic actions that
      are low in molecular weight and can permeate the blood-brain barrier are
      promising therapeutic agents against neurodegenerative diseases such as
      Alzheimer's disease. Carnosic acid (CA), an electrophilic compound in rosemary,
      activates antioxidant responsive element (ARE)-mediated transcription via
      activation of Nrf2. In the present study, we discovered that CA strongly promotes
      neurite outgrowth of PC12h cells. NGF as well as CA activated Nrf2, whereas CA
      and NGF-mediated neuronal differentiation was suppressed by Nrf2 knockdown. On
      the other hand, CA activated TrkA-downstream kinase Erk1/2 independently of Nrf2.
      CA-induced p62/ZIP expression in an Nrf2-dependent manner, while the CA-induced
      neural differentiation was suppressed by p62/ZIP knockdown. Furthermore, CA
      induced ARE activation was attenuated both by p62/ZIP knockdown and a Trk signal
      inhibitor. These results suggest that the CA induction of p62/ZIP by Nrf2
      enhances TrkA signaling which subsequently potentiates Nrf2 pathway. This is the
      first demonstration that activation of the Nrf2-p62/ZIP pathway by a low
      molecular natural electrophilic compound plays important roles in TrkA-mediated
      neural differentiation and may represent the common molecular mechanism for
      neurotrophic activities of electrophilic compounds.

PMID- 19762341
TI  - Bone morphogenetic protein receptors and signal transduction.
AB  - Bone morphogenetic proteins (BMPs) exhibit broad spectra of biological activities
      in various tissues, including bone, cartilage, blood vessels, heart, kidney,
      neurons, liver and lung. BMPs are members of the transforming growth factor-beta
      (TGF-beta) family that bind to type II and type I serine-threonine kinase
      receptors, and transduce signals through Smad and non-Smad signalling pathways.
      Recent findings have revealed that BMP signalling is finely tuned by various
      mechanisms in both positive and negative fashions. Perturbations of BMP
      signalling pathways are linked to a wide variety of clinical disorders, including
      vascular diseases, skeletal diseases and cancer. Administration of recombinant
      BMP ligands and increasing endogenous expression of BMPs provide therapeutic
      effects on some diseases. The recent development of BMP receptor inhibitors may
      also prove useful for some clinical diseases induced by hyperactivation of the
      BMP signalling pathways.

PMID- 19762342
TI  - Purification and some properties of wild-type and N-terminal-truncated
      ethanolamine ammonia-lyase of Escherichia coli.
AB  - The methods of homologous high-level expression and simple large-scale
      purification for coenzyme B(12)-dependent ethanolamine ammonia-lyase of
      Escherichia coli were developed. The eutB and eutC genes in the eut operon
      encoded the large and small subunits of the enzyme, respectively. The enzyme
      existed as the heterododecamer alpha(6)beta(6). Upon active-site titration with
      adeninylpentylcobalamin, a strong competitive inhibitor for coenzyme B(12), the
      binding of 1 mol of the inhibitor per mol of the alphabeta unit caused complete
      inhibition of enzyme, in consistent with its subunit structure. EPR spectra
      indicated the formation of substrate-derived radicals during catalysis and the
      binding of cobalamin in the base-on mode, i.e. with 5,6-dimethylbenzimidazole
      coordinating to the cobalt atom. The purified wild-type enzyme underwent
      aggregation and inactivation at high concentrations. Limited proteolysis with
      trypsin indicated that the N-terminal region is not essential for catalysis. His
      tagged truncated enzymes were similar to the wild-type enzyme in catalytic
      properties, but more resistant to p-chloromercuribenzoate than the wild-type
      enzyme. A truncated enzyme was highly soluble even in the absence of detergent
      and resistant to aggregation and oxidative inactivation at high concentrations,
      indicating that a short N-terminal sequence is sufficient to change the
      solubility and stability of the enzyme.

PMID- 19762343
TI  - Protruding masticatory (superfast) myosin heads from staggered thick filaments of
      dog jaw muscle revealed by X-ray diffraction.
AB  - To characterize the structure of jaw muscle fibres expressing masticatory
      (superfast) myosin, X-ray diffraction patterns of glycerinated fibres of dog
      masseter were compared with those of dog tibialis anterior in the relaxed state.
      Meridional reflections of masseter fibres were laterally broad, indicating that
      myosin filaments are staggered along the filament axis. Compared with tibialis
      anterior fibres, the peak of the first myosin layer line of masseter fibres was
      lower in intensity and shifted towards the meridian, while lattice spacings were
      larger at a similar sarcomere length. These suggest that the myosin heads of
      masticatory fibres are mobile, and tend to protrude from the filament shaft
      towards actin filaments. Lowering temperature or treating with N-phenylmaleimide
      shifted the peak of the first myosin layer line of tibialis anterior fibres
      towards the meridian and the resulting profile resembled that of masseter fibres.
      This suggests that the protruding mobile heads in the non-treated masticatory
      fibres are in the ATP-bound state. The increased population of weakly binding
      cross-bridges may contribute towards the high specific force of masticatory
      fibres during contraction. Electron micrographs confirmed the staggered alignment
      of thick filaments along the filament axis within sarcomeres of masticatory
      fibres, a feature that may confer efficient force development over a wide range
      of the sarcomere lengths.

PMID- 19762344
TI  - Inhibition of electron acceptance from ascorbate by the specific N
      carbethoxylations of maize cytochrome b561: a common mechanism for the
      transmembrane electron transfer in cytochrome b561 protein family.
AB  - Cytochromes b(561) constitute a novel class of proteins in eukaryotic cells with
      a number of highly relevant common features including six transmembrane alpha
      helices and two haem groups. Of particular interest is the presence of a large
      number of plant homologues having putative ascorbate- and monodehydroascorbate
      radical-binding sites. We conducted a diethylpyrocarbonate-modification study
      employing Zea mays cytochrome b(561) heterologously expressed in Pichia pastoris
      cells. Pre-treatment of cytochrome b(561) with diethylpyrocarbonate in oxidized
      form caused N-carbethoxylation of His(86), His(159) and Lys(83), leading to a
      drastic inhibition of the electron transfer from ascorbate. The activity was
      protected by the inclusion of ascorbate during the treatment. However, midpoint
      potentials of two haem centres did show only slight decreases upon the treatment,
      suggesting that changes in the midpoint potentials were not the major cause of
      the inhibition. Present results indicated that Zea mays cytochrome b(561)
      conducted an ascorbate-specific transmembrane electron transfer by utilizing a
      concerted H(+)/e(-) transfer mechanism and that the specific N-carbethoxylation
      of haem axial His(86) that would inhibit the removal of a proton from the bound
      ascorbate was a major cause of the inhibition. On the other hand, Lys(83) might
      be important for an initial step(s) of the fast electron acceptance from
      ascorbate.

PMID- 19762345
TI  - A lentiviral vector encoding two fluorescent proteins enables imaging of
      adenoviral infection via adenovirus-encoded miRNAs in single living cells.
AB  - MicroRNAs (miRNAs) are non-coding small RNAs that have been found in various
      kinds of eukaryotes and viruses. Recently, adenovirus non-coding RNAs, VA RNAs,
      have been reported to generate miRNAs. Here, we developed a lentiviral vector for
      monitoring adenovirus-derived miRNAs in living cells. By using red and green
      fluorescent proteins under the control of bi-directional two distinct promoters,
      adenoviral infection and consequent miRNA expression was successfully visualized
      and quantified by the reduction in green fluorescence when 3'-untranslated
      regions were connected to the target sequences of the adenovirus-derived miRNAs.
      Our functional analysis using a lentiviral vector is a useful method to examine
      the activity of miRNA in living mammalian cells.

PMID- 19762347
TI  - COMPASS: a program for generating serial samples under an infinite sites model.
AB  - SUMMARY: The program COMPASS can generate samples that have been collected at
      various points in time from a population that is evolving according to a Wright
      Fisher model. The samples are generated using coalescence simulations permitting
      various demographic scenarios and the program uses an infinite sites model to
      generate polymorphism data for the samples. By generating serially sampled
      population-genetic data, COMPASS allows investigating properties of polymorphism
      data that has been collected at different time points, and aid in making
      inference from ancient polymorphism data. AVAILABILITY: The program and the
      manual are available at:
      http://www.egs.uu.se/evbiol/Research/JakobssonLab/compass.html CONTACT:
      mattias.jakobsson@ebc.uu.se.

PMID- 19762346
TI  - Identifiability of isoform deconvolution from junction arrays and RNA-Seq.
AB  - MOTIVATION: Splice junction microarrays and RNA-seq are two popular ways of
      quantifying splice variants within a cell. Unfortunately, isoform expressions
      cannot always be determined from the expressions of individual exons and splice
      junctions. While this issue has been noted before, the extent of the problem on
      various platforms has not yet been explored, nor have potential remedies been
      presented. RESULTS: We propose criteria that will guarantee identifiability of an
      isoform deconvolution model on exon and splice junction arrays and in RNA-Seq. We
      show that up to 97% of 2256 alternatively spliced human genes selected from the
      RefSeq database lead to identifiable gene models in RNA-seq, with similar results
      in mouse. However, in the Human Exon array only 26% of these genes lead to
      identifiable models, and even in the most comprehensive splice junction array
      only 69% lead to identifiable models. SUPPLEMENTARY INFORMATION: Supplementary
      data are available at Bioinformatics online.

PMID- 19762348
TI  - PoreLogo: a new tool to analyse, visualize and compare channels in transmembrane
      proteins.
AB  - The increasing number of available atomic 3D structures of transmembrane channel
      proteins represents a valuable resource for better understanding their structure
      function relationships and to eventually predict their selectivity. Herein, we
      present PoreLogo, an automatic tool for analysing, visualizing and comparing the
      amino acid composition of transmembrane channels and its conservation across the
      corresponding protein family. AVAILABILITY: PoreLogo is accessible as a public
      web server at http://www.ebi.ac.uk/thornton-srv/software/PoreLogo/.

PMID- 19762349
TI  - Type II topoisomerases--inhibitors, repair mechanisms and mutations.
AB  - Type II topoisomerases are ubiquitous enzymes that play an essential role in the
      control of replicative DNA synthesis and share structural and functional homology
      among different prokaryotic and eukaryotic organisms. Antibacterial
      fluoroquinolones target prokaryotic topoisomerases at concentrations 100- to 1000
      fold lower than mammalian enzymes, the preferred targets of anticancer drugs such
      as etoposide. The mechanisms of action of both of these types of inhibitors
      involve the fixation of an intermediate reaction step, where the enzyme is
      covalently bound to an enzyme-mediated DNA double-strand break (DSB). The
      resulting ternary drug-enzyme-DNA complexes can then be converted to cleavage
      complexes that block further movement of the DNA replication fork, subsequently
      inducing stress responses. In haploid prokaryotic cells, stress responses include
      error-free and error-prone DNA damage repair pathways, such as homologous
      recombination and translesion synthesis, respectively. The latter can result in
      the acquisition of point mutations. Diploid mammalian cells are assumed to
      preferentially use recombination mechanisms for the repair of DSBs, an example of
      which, non-homologous end joining, is a major error-prone repair mechanism
      associated with an increased frequency of detectable small deletions, insertions
      and translocations. However, results obtained from safety testing of novel
      fluoroquinolones at high concentrations indicate that point mutations may also
      occur in mammalian cells. Recent data provide evidence for translesion synthesis
      catalysed by error-prone repair polymerases as a damage-tolerance repair
      mechanism of DSBs in eukaryotic cells. This paper discusses possible roles of
      different mechanisms for the repair of DSBs operating in both eukaryotic and
      prokaryotic cells that result in recombinational rearrangements,
      deletions/insertions as well as point mutations.

PMID- 19762350
TI  - The DNA repair gene APE1 T1349G polymorphism and cancer risk: a meta-analysis of
      27 case-control studies.
AB  - Published data regarding the association between the apurinic/apyrimidinic
      endonuclease 1 (APE1) T1349G (Asp148Glu) polymorphism and cancer risk show
      inconclusive results. To derive a more precise estimation of the relationship, we
      performed a meta-analysis of 27 published studies that included 12 432 cancer
      cases and 17 349 controls. We used odds ratios (ORs) and 95% confidence intervals
      (CIs) to evaluate the strength of the associations. The overall results suggested
      that the variant genotypes were associated with a moderately increased risk of
      all cancer types (OR = 1.09, 95% CI = 1.01-1.18 for TG versus TT; OR = 1.08, 95%
      CI = 1.00-1.18 for GG/TG versus TT). In the stratified analyses, the risk
      remained for studies of colorectal cancer, European populations and population
      based studies. Although some modest bias could not be eliminated, this meta
      analysis supported that the APE1 T1349G polymorphism is a low-penetrance risk
      factor for cancer development.

PMID- 19762351
TI  - Should spontaneous or timed intercourse guide couples trying to conceive?

PMID- 19762352
TI  - Actual versus desired family-centered practice in early intervention for children
      with hearing loss.
AB  - Early intervention programs (EIPs) for children with hearing loss (HL) are
      increasingly characterized by a growing family-centered orientation. This article
      examined mothers' and professionals' assessments of actual and desired parental
      involvement in 6 educational centers in Israel that implement an EIP for young
      children with HL and their parents. Hundred twenty mothers and 60 professionals
      participated in the study. Data were collected via FOCAS: Family Orientation of
      Community and Agency Services questionnaire (family and professional versions)
      that were initially designed in the United States for measuring the level of
      collaboration between professionals and parents in the course of early
      intervention. Descriptive statistics and t-test analyses were calculated. The
      findings indicated that parental involvement in the programs was perceived by
      mothers and professionals as satisfactorily family centered. However, these
      programs also need further improvements. Outcomes suggested that parents should
      be offered a wide range of services to respond to diverse needs, thus increasing
      parental motivation to become increasingly involved in EIPs.

PMID- 19762353
TI  - Physical activity, emotional and behavioural problems, maternal education and
      self-reported educational performance of adolescents.
AB  - This study examined whether physical activity, mental health and socio-economic
      position were associated with the overall academic performance and future
      educational plans of adolescents aged 15-16 years. We used a sample of 7002 boys
      and girls from the Northern Finland Birth Cohort 1986. Data were collected by a
      postal enquiry in 2001-02. Multivariable logistic regression models were
      estimated and adjusted for family structure and all variables in the models. In
      the fully adjusted models, higher levels of physical activity and high parental
      socio-economic position were associated with higher overall academic performance
      and future plans for higher education. High scoring on behavioural problems was
      related to lower overall academic performance and poorer future academic plans.
      In summary, a higher level of physical activity, fewer behavioural problems and
      higher socio-economic position were independently associated with high self
      perceived overall academic performance and plans for higher education among
      adolescents. The interrelations of these factors and the positive relationship
      between physical activity, mental health and school outcomes provide a context of
      critical importance for future research, intervention programming and policy
      directed at improving the educational attainment of adolescents.

PMID- 19762354
TI  - Interviewer effects in public health surveys.
AB  - Interviewer effects can have a substantial impact on survey data and may be
      particularly operant in public health surveys, where respondents are likely to be
      queried about racial attitudes, sensitive behaviors and other topics prone to
      socially desirable responding. This paper defines interviewer effects, argues for
      the importance of measuring and controlling for interviewer effects in health
      surveys, provides advice about how to interpret research on interviewer effects
      and summarizes research to date on race, ethnicity and gender effects.
      Interviewer effects appear to be most likely to occur when survey items query
      attitudes about sociodemographic characteristics or respondents' engagement in
      sensitive behaviors such as substance use. However, there is surprisingly little
      evidence to indicate whether sociodemographic interviewer-respondent matching
      improves survey response rates or data validity, and the use of a matched design
      introduces possible measurement bias across studies. Additional research is
      needed to elucidate many issues, including the influence of interviewers'
      sociodemographic characteristics on health-related topics, the role of within
      group interviewer variability on survey data and the simultaneous impact of
      multiple interviewer characteristics. The findings of such research would provide
      much-needed guidance to public health professionals on whether or not to match
      interviewers and respondents on key sociodemographic characteristics.

PMID- 19762355
TI  - Containing costs and improving care for children in Medicaid and CHIP.
AB  - The current health reform debate is greatly concerned with "bending the curve" of
      cost growth and containing costs, particularly in public programs. Our research
      demonstrates that spending in Medicaid and the Children's Health Insurance
      Program (CHIP) is highly concentrated, particularly among children with chronic
      health problems. Ten percent of enrollees (two-thirds of whom have a chronic
      condition) account for 72 percent of the spending; 30 percent of enrolled
      children receive little or no care. These results highlight the importance of
      cost containment strategies that reduce avoidable hospitalizations among children
      with chronic problems and policies that increase preventive care, particularly
      among African American children.

PMID- 19762356
TI  - Portrait of a policy and political entrepreneur.

PMID- 19762357
TI  - Senator Edward M. Kennedy: the master legislative craftsman.

PMID- 19762358
TI  - Senator Edward M. Kennedy: making common cause with adversaries while committed
      to health reform.

PMID- 19762359
TI  - Patient and rheumatologist perspectives on glucocorticoids: an exercise to
      improve the implementation of the European League Against Rheumatism (EULAR)
      recommendations on the management of systemic glucocorticoid therapy in rheumatic
      diseases.
AB  - OBJECTIVE: To explore perspectives among patients and rheumatologists on
      glucocorticoid (GC) therapy and European League Against Rheumatism (EULAR)
      recommendations on the management of systemic GC therapy in order to enhance
      implementation of the recommendations. METHODS: Rheumatologists (from eight
      countries) and patients (from five countries) acquainted with GCs participated in
      separate meetings, during which positive and negative aspects of GC therapy were
      discussed and possible adverse events (AEs) were ranked for importance; in
      addition participants were asked to evaluate the published EULAR recommendations.
      The reports from these meetings and themes related to implementation of the
      recommendations were discussed during an international forum of the experts who
      had formulated the recommendations and patient participants. RESULTS: In all, 140
      patients (78% women; mean age 53 years; 61% patients with rheumatoid arthritis)
      and 110 rheumatologists (mean work experience 15 years) participated in the
      meetings. Osteoporosis, diabetes and cardiovascular diseases were ranked among
      the five most worrisome AEs by patients and rheumatologists. In both groups,
      there was agreement with most of the recommendations; the recommendations on GC
      information cards and GC use during pregnancy scored lowest. Ideas to improve
      implementation of the recommendations and a research agenda were generated.
      CONCLUSION: The patient and rheumatologist views on GCs corresponded to a large
      extent, reflected by concerns in both groups about osteoporosis, diabetes and
      cardiovascular diseases. Specific problems with the EULAR recommendations were
      identified and addressed to improve their implementation. This exercise shows
      that patient and rheumatologist perspectives should be included early in the
      process of formulating recommendations.

PMID- 19762360
TI  - A STAT4 risk allele is associated with ischaemic cerebrovascular events and anti
      phospholipid antibodies in systemic lupus erythematosus.
AB  - OBJECTIVE: To investigate whether the risk allele for systemic lupus
      erythematosus (SLE) in the signal transducer and activator of transcription
      factor 4 (STAT4) gene, defined by the single nucleotide polymorphism (SNP)
      rs10181656(G), is associated with vascular events and/or presence of
      prothrombotic anti-phospholipid antibodies (aPL) in patients with SLE. METHODS:
      Two independent groups of unrelated patients with SLE of Swedish ethnicity (n=424
      and 154) were genotyped, and occurrence of previous manifestations of ischaemic
      heart disease (IHD), ischaemic cerebrovascular disease (ICVD) and venous
      thromboembolic events (VTE) was tabulated. aPL values were measured by ELISA.
      Matched controls (n=492 and 194) were genotyped. RESULTS: The STAT4 risk allele
      was more frequent in patients with SLE with previous arterial events (combined OR
      (OR(c))=1.5, 95% CI 1.1 to 2.0) compared to patients without such events. The
      association was mainly attributable to an accumulation of the risk allele among
      patients with ICVD (OR(c)=2.3, CI 1.6 to 3.3). There was no association with IHD
      or VTE. The presence of two or more aPLs was associated with the risk allele
      (OR(c)=1.6, 95% CI 1.2 to 2.0). In multivariable-adjusted logistic regression
      analyses treatment for hypertension, at least one STAT4 risk allele, older age,
      IgG anti-cardiolipin antibodies and longer SLE duration remained independently
      associated with previous ICVD (p<or=0.02 for all). CONCLUSION: Patients with SLE
      with the STAT4 risk allele had a strikingly increased risk of ICVD, comparable in
      magnitude to that of hypertension. The results imply that a genetic
      predisposition is an important and previously unrecognised risk factor for ICVD
      in SLE, and that aPLs may be one underlying mechanism.

PMID- 19762361
TI  - EULAR evidence-based recommendations for the diagnosis of knee osteoarthritis.
AB  - OBJECTIVE: To develop evidence-based recommendations for the diagnosis of knee
      osteoarthritis (OA). METHODS: The multidisciplinary guideline development group,
      representing 12 European countries, generated 10 key propositions regarding
      diagnosis using a Delphi consensus approach. For each recommendation, research
      evidence was searched systematically. Whenever possible, the sensitivity,
      specificity and likelihood ratio were calculated for individual diagnostic
      indicators and a diagnostic ladder was developed using Bayes' method. Secondary
      analyses were undertaken to test directly the recommendations using multiple
      predictive models in two populations from the UK and the Netherlands. Strength of
      recommendation was assessed by the EULAR visual analogue scale. RESULTS:
      Recommendations covered the definition of knee OA and its risk factors, subsets,
      typical symptoms and signs, the use of imaging and laboratory tests and
      differential diagnosis. Three symptoms (persistent knee pain, limited morning
      stiffness and reduced function) and three signs (crepitus, restricted movement
      and bony enlargement) appeared to be the most useful. Assuming a 12.5% background
      prevalence of knee OA in adults aged > or =45 years, the estimated probability of
      having radiographic knee OA increased with increasing number of positive
      features, to 99% when all six symptoms and signs were present. The performance of
      the recommendations in the study populations varied according to the definition
      of knee OA, background risk and number of tests applied. CONCLUSION: 10 key
      recommendations for diagnosis of knee OA were developed using both research
      evidence and expert consensus. Although there is no agreed reference standard,
      thorough clinical assessment alone can provide a confident rule-in diagnosis.

PMID- 19762362
TI  - The SLC22A12 gene is associated with gout in Han Chinese and Solomon Islanders.

PMID- 19762363
TI  - Evaluation of the appropriateness of composite disease activity measures for
      assessment of psoriatic arthritis.
AB  - OBJECTIVE: Specific composite indices assessing disease activity in psoriatic
      arthritis (PsA) have not yet been sufficiently validated. The objective of this
      study was to identify instruments best reflecting disease activity in PsA.
      METHODS: Measures for inclusion in clinical trials, as recommended by the OMERACT
      7/8 PsA workshops, were assessed. A principal component analysis (PCA) was
      performed with cross-sectional data of 105 patients with PsA to identify a
      minimal set of important dimensions for a disease activity assessment tool for
      PsA. This was compared with components contained in existing composite indices.
      RESULTS: The PCA revealed four principal components best reflecting disease
      activity. The first contained patient global and pain assessment; the second
      contained 66/68 swollen and tender joint counts as main variables; C-reactive
      protein (CRP) best loaded to the third component; and the fourth was loaded by
      skin assessment but did not reach significance. When comparing the three
      significant principal components with items of established composite measures,
      they were best covered by the Disease Activity Index for Reactive Arthritis
      (DAREA) which comprises patient pain and global assessments, 66/68 joint counts
      and CRP. CONCLUSION: Among the currently available indices used in arthritic
      conditions, the DAREA best reflects the domains found to be important in PsA.

PMID- 19762364
TI  - Neutrophil-derived S100A12 as novel biomarker of inflammation in familial
      Mediterranean fever.
AB  - OBJECTIVE: Familial Mediterranean fever (FMF) is characterised by recurrent
      periodic febrile attacks and persistent subclinical inflammation. The damage
      associated molecular pattern (DAMP) protein S100A12 has proven to be a sensitive
      marker for disease activity and inflammation in numerous inflammatory disorders.
      The aim of this study was to analyse the role of S100A12 in the detection of
      inflammation in patients with FMF. METHODS: 52 children and adolescents with a
      clinical and/or genetic diagnosis of FMF were prospectively followed-up over 18
      months (in total 196 visits). During clinical visits, erythrocyte sedimentation
      rate, C reactive protein, serum amyloid A and S100A12 serum concentrations were
      determined. Patients were categorised into four groups according to the clinical
      activity of FMF. RESULTS: Serum concentrations of S100A12 were excessively
      increased in patients with a mean increase of about 290-fold in active FMF above
      normal controls. S100A12 decreased significantly after introduction of colchicine
      therapy. Serum concentrations of S100A12 were significantly higher in patients
      treated with colchicine with persistent symptoms (mean+/-SEM, 6260+/-2120 ng/ml)
      than in those with clinically controlled disease (440+/-80 ng/ml, p<0.001). In
      contrast to classical markers of inflammation, S100A12 was significantly elevated
      in clinically unaffected homozygous MEFV gene mutation carriers, indicating
      subclinical inflammation. CONCLUSIONS: S100A12 is a valuable biomarker for
      monitoring disease activity, inflammation and response to colchicine treatment in
      patients with FMF. It might even be more sensitive in detecting subclinical
      inflammation than other available indicators.

PMID- 19762365
TI  - High frequency ultrasound measurement of digital dermal thickness in systemic
      sclerosis.
AB  - BACKGROUND: Currently, assessment of dermal thickness in systemic sclerosis (SSc)
      is performed by palpation and assessment using the modified Rodnan skin score
      (mRSS). OBJECTIVE: To verify whether high frequency ultrasound (US) may be a
      reliable and a reproducible method to measure digital dermal thickness. METHODS:
      In 70 patients with SSc, skin thickness was evaluated with US by 2 observers at 2
      different sites on the second digit of the dominant limb to determine the
      interobserver variability. Patients and controls were examined twice by the first
      observer for intraobserver variability. Patients were divided into three
      subgroups according to the phase of the disease (oedematous, fibrotic or
      atrophic). RESULTS: At both examined areas, US showed a significant dermal
      thickening (p<0.001) in the whole group of patients with SSc. A low intraobserver
      and interobserver variability was found. A highly significant correlation between
      the global mRSS and the local dermal thickness at the two examined sites
      (p=0.032, p=0.021) was detected. Skin thickness was significantly higher in the
      oedematous than in the fibrotic group (p<0.001) and significantly higher in the
      fibrotic and the oedematous group (p<0.001) than in the atrophic group (p<0.002).
      CONCLUSIONS: US is a reliable tool giving reproducible results, and is able to
      detect digital dermal thickening in SSc.

PMID- 19762366
TI  - Subchondral bone attrition may be a reflection of compartment-specific mechanical
      load: the MOST Study.
AB  - INTRODUCTION: Subchondral bone attrition (SBA), a feature of osteoarthritis, may
      be caused by excess focal load to bone, and/or inadequate bone quality to
      withstand loads through the joint. This study evaluated the effects of
      malalignment, which can cause focal excessive load, and systemic bone density on
      the presence and incidence of SBA. METHODS: The Multicenter Osteoarthritis Study
      is a cohort of individuals who have or are at high risk of knee osteoarthritis.
      Baseline alignment and bone mineral density (BMD) measures were assessed.
      Baseline and 30-month knee magnetic resonance images were graded for SBA (grade 0
      3) using the whole-organ magnetic resonance imaging score. The study evaluated
      the association of alignment in medial and lateral compartments, respectively,
      and systemic BMD with baseline presence of SBA and incident SBA using logistic
      regression and adjusting for age, sex and body mass index. RESULTS: Of 1253
      participants (mean age 62 years, mean BMI 30, 61% women), 33% had baseline SBA
      and 44% had knee osteoarthritis. Associations between the presence and incidence
      of SBA with malalignment in both compartments were noted (odds ratios (95% CI)
      2.9 (2.1 to 4.0) and 1.9 (1.2 to 2.9), respectively, for varus knees in the
      medial compartment; 4.5 (2.8 to 7.1) and 2.1 (1.1 to 4.1), respectively, for
      valgus knees in the lateral compartment). Low BMD was not associated with SBA.
      CONCLUSIONS: The presence and incidence of SBA are associated with malalignment
      in a compartment-specific manner, but not with low BMD. SBA may be a marker of
      increased load experienced by overlying cartilage, which may contribute to
      increased forces transmitted to the cartilage due to alteration in subchondral
      bone.

PMID- 19762367
TI  - Working together--primary care doctors' and nurses' attitudes to collaboration.
AB  - BACKGROUND: Multidisciplinary teamwork is recommended for various disorders and
      it has been suggested that it is a way to meet the new challenges and demands
      facing general practitioners (GPs) in modern society. Attempts to introduce the
      method in primary care have failed partly due to GPs' unwillingness to
      participate. The aim of this study was to measure attitudes towards collaboration
      among GPs and district nurses (DN) and to investigate whether there is a
      correlation between a positive attitude toward collaboration and high self-esteem
      in the professional role. METHODS: The Jefferson Scale of Attitudes toward
      Physician Nurse Collaboration and the Professional Self-Description Form (PSDF)
      was used to study a cohort of 600 GPs and DNs in Vastra Gotaland region. The
      purpose was to map differences and correlations of attitude between DNs and GPs,
      between male and female GPs, and between older and younger DNs and GPs. RESULTS:
      Four hundred and one answers were received. DNs (mean 51.7) were significantly
      more positive about collaboration than GPs (mean 49.4). There was no difference
      between younger and older, male and female GPs. DNs scored higher on the PSDF
      scale than GPs. CONCLUSIONS: DNs were slightly more positive about collaboration
      than GPs. A positive attitude towards collaboration did not seem to be a part of
      the GPs' professional role to the same extent as it is for DNs. Professional
      norms seem to have more influence on attitudes than do gender roles. DNs seem
      more confident in their profession than GPs.

PMID- 19762368
TI  - Bereavement needs assessment in specialist palliative care: a review of the
      literature.
AB  - Bereavement needs assessment for specialist palliative care services has been
      highlighted as important by NICE guidance on palliative care for adults with
      cancer. Identifying and implementing appropriate bereavement measurement tools
      has remained a challenge. This paper identifies and reviews bereavement
      measurement tools to determine their suitability for use within bereavement
      services and hospice settings. Cochrane, MEDLINE, PsycINFO and CINAHL, electronic
      databases were searched, yielding 486 papers. From fifty-nine full text papers
      appraised, 10 measurement tools were analysed in detail. Some tools had been
      tested on specific populations which limited transferability to specialist
      palliative care settings; some lacked adequate theoretical links and were not
      effective in discriminating between normal and complicated grief reactions; and
      some lacked clear evidence of validity or reliability. Based on these criteria,
      conclusions are drawn about the suitability of particular tools for UK
      bereavement services and hospice settings where intervention is delivered by both
      trained professionals and volunteers.

PMID- 19762369
TI  - Governance in changing times: the experiences of hospice trustees in the United
      Kingdom.
AB  - Hospice trustees are volunteers who are vital to the governance and management of
      independent, charitable hospices, yet little is known about their roles and
      concerns. This paper presents some findings from a qualitative study which
      explored the views and perspectives of hospice trustees in the UK. Twenty hospice
      trustees took part in semi-structured telephone interviews, which were analysed
      using an iterative thematic approach. Nine themes emerged from the analysis, and
      were grouped into two major categories. One theme, 'becoming a trustee', is
      presented in this paper to illustrate trustees' concerns about the challenges
      they face in adapting to change. The pace of change currently facing hospices in
      the UK is an issue of particular concern to trustees, presenting ongoing
      challenges for this group of volunteers. The study also raises wider questions
      about how hospices wish to position themselves in the future.

PMID- 19762370
TI  - Physical, psychological, and functional comorbidities of multisymptom illness in
      Australian male veterans of the 1991 Gulf War.
AB  - Multisymptom illness is more prevalent in 1991 Gulf War veterans than in military
      comparison groups; less is known about comorbidities. The authors compared
      physical, psychological, and functional comorbidities in Australian male Gulf War
      I veterans with those in actively (non-Gulf) deployed and nondeployed military
      personnel by using a questionnaire and medical assessment in 2000-2002.
      Multisymptom illness was more common in male Gulf War veterans than in the
      comparison group (odds ratio (OR) = 1.80, 95% confidence interval (CI): 1.48,
      2.19). Stratifying by deployment status in the comparison group made little
      difference in this association. Gulf War veterans with multisymptom illness had
      increased psychiatric disorders, including major depression (OR = 6.31, 95% CI:
      4.19, 9.52) and posttraumatic stress disorder (OR = 9.77, 95% CI: 5.39, 18.59);
      increased unexplained chronic fatigue (OR = 13.32, 95% CI: 7.70, 23.05); and more
      reported functional impairment and poorer quality of life, but objective physical
      and laboratory outcomes were similar to those for veterans without multisymptom
      illness. Similar patterns were found in the comparison groups; differences across
      the 3 groups were statistically significant for only hospitalization, obstructive
      liver disease, and Epstein-Barr virus exposure. Multisymptom illness is more
      prevalent in Gulf War I veterans, but the pattern of comorbidities is similar for
      actively deployed and nondeployed military personnel.

PMID- 19762371
TI  - Vitamin D status and the risk of cardiovascular disease death.
AB  - Accumulating evidence suggests that inadequate vitamin D levels may predispose
      people to chronic diseases. The authors aimed to investigate whether serum 25
      hydroxyvitamin D (25(OH)D) level predicts mortality from cardiovascular disease
      (CVD). The study was based on the Mini-Finland Health Survey and included 6,219
      men and women aged > or =30 years who were free from CVD at baseline (1978-1980).
      During follow-up through 2006, 640 coronary disease deaths and 293
      cerebrovascular disease deaths were identified. Levels of 25(OH)D were determined
      from serum collected at baseline. Cox's proportional hazards model was used to
      assess the association between 25(OH)D and risk of CVD death. After adjustment
      for potential confounders, the hazard ratio for total CVD death was 0.76 (95%
      confidence interval (95% CI): 0.60, 0.95) for the highest quintile of 25(OH)D
      level versus the lowest. The association was evident for cerebrovascular death
      (hazard ratio = 0.48, 95% CI: 0.31, 0.75) but not coronary death (hazard ratio =
      0.91, 95% CI: 0.70, 1.18). A low vitamin D level may be associated with higher
      risk of a fatal CVD event, particularly cerebrovascular death. These findings
      need to be replicated in other populations. To demonstrate a causal link between
      vitamin D and CVD, randomized controlled trials are required.

PMID- 19762372
TI  - Hypothesis-driven candidate gene association studies: practical design and
      analytical considerations.
AB  - Candidate gene association studies (CGAS) are a useful epidemiologic approach to
      drawing inferences about relations between genes and disease, especially when
      experimental data support the involvement of specific biochemical pathways. The
      value of CGAS is apparent when allele frequencies are low, effect sizes are
      small, or the study population is limited or unique. CGAS is also valuable for
      validating previous reports of genetic associations with disease in different
      populations. Despite the many advantages, the information generated from CGAS is
      sometimes compromised because of either inefficient study design or suboptimal
      analytical approaches. Here the authors discuss issues related to the study
      design and statistical analyses of CGAS that can help to optimize their
      usefulness and information content. These issues include judicious hypothesis
      driven selection of biochemical pathways, genes, and single nucleotide
      polymorphisms, as well as appropriate quality control and analytical procedures
      for measuring main effects and for evaluating environmental exposure
      modifications and interactions. A study design algorithm using the example of DNA
      repair genes and cancer is presented for purposes of illustration.

PMID- 19762373
TI  - Using a longitudinal model to estimate the effect of methicillin-resistant
      Staphylococcus aureus infection on length of stay in an intensive care unit.
AB  - Health-care-associated methicillin-resistant Staphylococcus aureus (MRSA)
      infection may cause increased hospital stay, or sometimes death. Quantifying this
      effect is complicated because the exposure is time dependent: infection may
      prolong hospital stay, while longer stays increase infection risk. In this paper,
      the authors overcome these problems by using a multinomial longitudinal model to
      estimate the daily probability of death and discharge. They then extend the basic
      model to estimate how the effect of MRSA infection varies over time and to
      quantify number of excess days in the intensive care unit due to infection. They
      found that infection decreased the relative risk of discharge (relative risk
      ratio = 0.68, 95% credible interval: 0.54, 0.82). Infection on the first day of
      admission resulted in a mean extra stay of 0.3 days (95% credible interval: 0.1,
      0.5) for a patient with an Acute Physiology and Chronic Health Evaluation II
      score of 10 and 1.2 days (95% credible interval: 0.5, 2.0) for a patient with a
      score of 30. The decrease in the relative risk of discharge remained fairly
      constant with day of MRSA infection but was slightly stronger closer to the start
      of infection. Results confirm the importance of MRSA infection in increasing stay
      in an intensive care unit but suggest that previous work may have systematically
      overestimated the effect size.

PMID- 19762374
TI  - The origin of mixed connective tissue disease: a stimulus for autoimmune disease
      research.

PMID- 19762376
TI  - Ultraviolet B exposure of peripheral blood mononuclear cells of patients with
      systemic lupus erythematosus inhibits DNA methylation.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease, in
      which sunlight (especially ultraviolet B (UVB) 290-320 nm) is known to induce
      exacerbation of disease. DNA methylation regulates gene expression, and
      hypomethylation is associated with abnormal cell function in SLE. The purpose of
      this study was to investigate the effect of UVB on DNA methylation in SLE and its
      significance in the pathogenesis of SLE. Forty-five patients with SLE and 20
      healthy controls were enrolled in the study, which involved the investigation of
      DNA methylation and DNA methyltransferase 1 (DNMT1) of peripheral blood
      mononuclear cells with UVB irradiation. Our results demonstrate the following:
      The level of DNA methylation in patients with SLE was lower than that in the
      control group. DNA methylation was decreased after UVB irradiation at different
      dosages especially in patients with marlar rashes and leucopenia, but no
      significant difference was observed in the DNMT1 mRNA expression. DNA methylation
      levels in patients with active SLE were more sensitive to UVB. In conclusion, UVB
      exposure is able to inhibit DNA methylation, which subsequently takes part in the
      pathogenesis of SLE.

PMID- 19762375
TI  - Validation of the Spanish, Portuguese and French versions of the Lupus Damage
      Index questionnaire: data from North and South America, Spain and Portugal.
AB  - We have previously developed and validated a self-administered questionnaire,
      modelled after the Systemic Lupus International Collaborating Clinics Damage
      Index (SDI), the Lupus Damage Index Questionnaire (LDIQ), which may allow the
      ascertainment of this construct in systemic lupus erythematosus (SLE) patients
      followed in the community and thus expand observations made about damage. We have
      now translated, back-translated and adapted the LDIQ to Spanish, Portuguese and
      French and applied it to patients followed at academic and non-academic centres
      in North and South America, Portugal and Spain while their physicians scored the
      SDI. A total of 887 patients (659 Spanish-speaking, 140 Portuguese-speaking and
      80 French-speaking patients) and 40 physicians participated. Overall, patients
      scored all LDIQ versions higher than their physicians (total score and all
      domains). Infrequent manifestations had less optimal clinimetric properties but
      overall agreement was more than 95% for the majority of items. Higher
      correlations were observed among the Spanish-speaking patients than the
      Portuguese-speaking and French-speaking patients; further adjustments may be
      needed before the Portuguese and French versions of the LDIQ are applied in
      community-based studies. The relationship between the LDIQ and other outcome
      parameters is currently being investigated in a different patient sample.

PMID- 19762377
TI  - IAN5 polymorphisms are associated with systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a representative autoimmune disease, which
      is frequently associated with lymphopenia. Biobreeding (BB) rat is a typical
      animal model which develops autoimmune diseases with lymphopenia which results
      from a frame-shift mutation in the immune-associated nucleotide (IAN) 5 gene.
      IAN5 is involved in the regulation of T-cell activation and survival. To examine
      the association of IAN5 gene with SLE, we scrutinised the single nucleotide
      polymorphisms (SNPs) in the IAN5 gene. We conducted a case-control study where
      132 SLE patients, 505 rheumatoid arthritis (RA) patients, and 546 controls were
      genotyped for four SNPs in the IAN5 gene. Two SNPs (+2071C > T and +2677G > A)
      were associated with susceptibility to SLE (P = 0.040 and 0.045, respectively),
      and -4432G > A SNP was associated with the development of leukopenia (P = 0.028)
      and the requirement of steroid pulse therapy (P = 0.040) in SLE patients.
      Haplotype analyses showed that Ht1(CTCG) was associated with susceptibility to
      SLE (P = 0.036), and Ht4(ACCG), Ht5(ACTA) and Ht6(GCCG) were associated with the
      development of nephritis (P = 0.017, 0.019, 0.022, respectively). In conclusion,
      the IAN5 polymorphisms were associated with susceptibility to SLE and the
      development of clinical disease manifestations in a strictly Korean population.

PMID- 19762378
TI  - Pulmonary involvement of systemic lupus erythematosus: analysis of 90 necropsies.
AB  - Pleuropulmonary manifestations of systemic lupus erythematosus (SLE) have been
      reported to be of variable prevalence, depending on the diagnostic methods used.
      The objective of this study was to determine the anatomopathological prevalence
      and the nature of lung involvement associated with SLE and to define if there
      were differences in the grade and type of pulmonary involvement in patients who
      had died at different time periods, before or after 1996. Complete autopsy
      studies of 90 patients with SLE diagnosis carried out between 1958 and 2006 and
      their clinical records were studied. All patients fulfilled the American College
      of Rheumathology (ACR) diagnostic criteria for SLE. Two groups of patients were
      analyzed: patients who had died before 1996 and those deceased in 1996-2006. Some
      pleuropulmonary involvement was detected in 97.8% of the autopsies. The most
      frequent findings were pleuritis (77.8%), bacterial infections (57.8%), primary
      and secondary alveolar haemorrhages (25.6%), followed by distal airway
      alterations (21.1%), opportunistic infections (14.4%) and pulmonary
      thromboembolism (7.8%), both acute and chronic. No cases of acute or chronic
      lupus pneumonitis were found. Opportunistic lung infections were invasive
      aspergillosis, disseminated strongyloidiasis, mucormicosis and Pneumocystis
      carinii. Only three of 23 patients with alveolar haemorrhage showed capillaritis.
      The four patients with primary pulmonary hypertension (PHT) had plexiform
      lesions. Deceased patients' age at death (46.09 +/- 11.01 vs 30.3 +/- 11.5 years,
      P < 0.0001) as well as survival time from diagnosis date (11.8 +/- 11.2 vs 4.4 +/
      4.9 years, P < 0.0001) in the second time period evaluated were significantly
      higher. However, there were no statistically significant differences in the
      prevalence of any of the pulmonary manifestations. Sepsis was considered the
      major cause of death without significant differences in both groups. Our results
      show that pulmonary manifestations directly caused by systemic lupus
      erythematosus are very uncommon and that their prevalence has not changed in the
      past 10 years. Pulmonary infection is still the most frequent affection, and it
      is an important cause of death in patients with lupus.

PMID- 19762379
TI  - Treatment of femoral head osteonecrosis in patients with systemic lupus
      erythematosus by free vascularised fibular grafting.
AB  - The purpose of this study was to review the radiographs of symptomatic femoral
      head osteonecrosis in patients with systemic lupus erythematosus (SLE) and to
      assess the results of treatment using free vascularised fibular grafting. We
      retrospectively reviewed 50 patients (80 hips) with SLE who underwent free
      vascularised fibular grafting for osteonecrosis of the femoral head. All patients
      were followed up for at least 2 or more years (average, 4.3 years). The mean
      Harris hip score improved from 72 to 88. At the latest follow-up, we found
      improved or unchanged radiographs in 12 of initially Stage II hips and in 60 of
      64 Stage III or IV hips. No hips failed treatment and underwent total hip
      arthroplasty. The data suggest that free vascularised fibular grafting was
      successful in maintaining joint function and in delaying the need for joint
      replacement procedure.

PMID- 19762380
TI  - Expression profile of HIN200 in leukocytes and renal biopsy of SLE patients by
      real-time RT-PCR.
AB  - HIN200 is a human IFN-inducible gene and homologous to murine IFI202 gene, which
      was identified as a candidate gene for SLE susceptibility in lupus mouse model.
      We determined these gene expressions in leukocytes from 20 SLE patients and 10
      healthy controls and in renal biopsies from 29 SLE patients and 15 kidney donors
      using sensitive real-time reverse transcriptase-polymerase chain reaction (RT
      PCR). The expressions of MNDA, IFIX, IFI16 and AIM2 genes significantly increased
      in leukocytes but not in kidney biopsies from SLE patients as compared to the
      control individuals, with P = 0.0003, P = 0.0056, P = 0.0002 and P < 0.0001,
      respectively. We also assessed the expression profiles of IFIX and IFI16 isoforms
      using semi-quantitative RT-PCR. We found up-regulation of B isoform (short
      product) of IFI16 in SLE patients. In addition, the expression levels were
      analyzed in correlation with disease activity and clinical characteristics.
      Interestingly, higher expression of MNDA was observed in patients who were
      positive for anti-dsDNA antibodies than in patients who were negative (P =
      0.0276). In conclusion, it is suggested that the HIN200 genes have a role in SLE
      pathogenesis. Our study also observed a possible important role of a specific
      short isoform of IFI16 as well as a link between MNDA and anti-dsDNA antibody
      production.

PMID- 19762381
TI  - Class IV-G and IV-S lupus nephritis in Chinese patients: a large cohort study
      from a single center.
AB  - This study is to assess the difference between IV-G and IV-S in a large cohort of
      Chinese patients with lupus nephritis. The detailed data of patients with
      subclass IV-G and IV-S were retrospectively analyzed. Serum ANCA and anti-C1q
      antibodies were detected. A total of 172 cases were classified as class IV,
      including 152 cases with IV-G and 20 cases with IV-S. In IV-S, the level of
      haemoglobin was significantly higher (P = 0.024), proteinuria was milder (P =
      0.003), serum creatinine was lower (P = 0.021), serum C3 was higher (P = 0.045)
      and the ratio of positive serum anti-cardiolipin antibodies was higher (P =
      0.014). On pathological evaluation, the ratio of glomerular fibrinoid necrosis
      was significantly higher (P = 0.006) and the score of endocapillary
      hypercellualrity, interstitial inflammation and total activity indices was
      significantly lower (P < 0.001, P = 0.01, P = 0.006, respectively) in IV-S. The
      frequency of serum ANCA was significantly higher in IV-S than that in IV-G (20 vs
      4.6%, P = 0.008). The frequencies of anti-C1q IgG1 and IgG3 subclass were
      significantly higher in IV-G (P = 0.006, P = 0.011, respectively). There are
      significant differences in clinical and pathological manifestations between IV-S
      and IV-G lupus nephritis which need further investigation.

PMID- 19762382
TI  - Extracorporeal shockwave for hip necrosis in systemic lupus erythematosus.
AB  - Patients with systemic lupus erythematosus (SLE) frequently received
      corticosteroid therapy, resulting in osteonecrosis of the femoral head (ONFH).
      Prior studies demonstrated the effectiveness of extracorporeal shockwave
      treatment (ESWT) for ONFH.. This study evaluated the effectiveness of ESWT for
      ONFH in patients with SLE. We studied 39 patients, including 15 patients with SLE
      (26 hips) and 24 controls (29 hips). To each affected hip we applied ESWT (6000
      impulses at 28 kV in a single session). Patients were ambulated with partial
      weight bearing for 4-6 weeks. The primary endpoint was the need for hip
      replacement. The secondary endpoints were improvement in hip pain and function
      and image changes on X-ray and MRI. Patients received total hip replacement in
      12% of patients with SLE and in 14% of controls (P = 0.802). There was no
      statistically significant difference in pain scores (0.86 vs. 0.89; P = 0.467)
      and function scores (89% vs. 91%; P = 0.194) between patients with SLE and
      controls. SLE response to ESWT for ONFH is comparable with ONFH in patients
      without SLE.

PMID- 19762383
TI  - Elevated levels of serum antibodies against Saccharomyces cerevisiae mannan in
      patients with systemic lupus erythematosus.
AB  - This study was undertaken to investigate whether levels of anti-Saccharomyces
      cerevisiae mannan antibodies (ASCMAs), a serological marker for Crohn's disease,
      seronegative spondyloarthritis and Behcet's disease, also correlate with systemic
      lupus erythematosus (SLE) in humans. Serum samples from healthy volunteers (n =
      152) and patients with SLE (n = 40) were compared for ASCMA-IgA, -IgG and -IgM
      levels using enzyme linked immunosorbent assays. ASCMA-IgG, but not IgM and IgA,
      prevalence was significantly raised in active SLE patients (57.5%) compared with
      healthy controls (8.5%). ASCMA-IgG levels in SLE patients during remission were
      relatively lower, indicating a possible correlation with disease activity. These
      results differ from a previous study, which did not detect a difference between
      ASCMA levels in SLE patients and healthy control. It remains to be evaluated
      whether elevated ASCMA-levels are common to all rheumatic disorders.

PMID- 19762384
TI  - Very long-term outcome of pure lupus membranous nephropathy treated with
      glucocorticoid and azathioprine.
AB  - The aim of this study is to report the long-term outcome of pure membranous lupus
      nephropathy (MLN) treated with glucocorticoid and azathioprine (AZA). A cohort of
      patients with SLE who had biopsy-confirmed pure MLN was treated initially with
      prednisone (0.8-1.0 mg/kg/day) and AZA (targeted to 2 mg/kg/day). Patients were
      followed for the following outcomes: remission rate at 12 months, renal flares,
      extra-renal flares and renal function deterioration. The cumulative risks of
      renal flares and renal function decline were studied by Kaplan-Meier analysis.
      Thirty-eight patients were studied (31 women; age 35.0 +/- 9.2 years; mean SLE
      duration 48.5 +/- 59 months; WHO Class Va 45%, Vb 55%). Twenty-two (58%) patients
      were nephrotic and four (11%) were hypertensive at presentation. All patients
      were treated with prednisolone (0.85 +/- 0.24 mg/kg/day) and AZA (1.72 +/- 0.43
      mg/kg/day). At 12 months, 24 (67%) patients achieved complete response (CR), 8
      (22%) had partial response (PR) and 4 (11%) were treatment resistant. After a
      follow-up of 12 +/- 5.8 years, 19 episodes of renal flares (15 proteinuric and 4
      nephritic) occurred in 13 (34%) patients. The cumulative risks of renal flares at
      5, 10 and 15 years were 19.4, 32.0 and 36.8%, respectively. Retreatment with an
      augmented dosage of prednisolone, +/- another immunosuppressive agent, resulted
      in CR and PR in 15 (79%) and 4 (21%) of these flare episodes, respectively. At
      last visit, three (8%) patients had doubling of serum creatinine, whereas six
      (16%) patients had decline of creatinine clearance by >/=30% (none developed end
      stage renal failure). Seven episodes of thromboembolic complications occurred in
      five (13%) patients and 11 episodes of infective complications (five major, six
      minor) were reported in seven (18%) patients. In the absence of co-existing
      proliferative lesions, MLN runs a relatively benign course with low risk of renal
      function deterioration. Treatment with high-dose prednisolone and AZA is
      effective, inexpensive and well-tolerated. Prolonged observation shows that one
      of three patients develop renal flares, which are often proteinuric and
      responsive to reinduction therapy.

PMID- 19762385
TI  - Antithyroid antibodies in antiphospholipid syndrome: prevalence and clinical
      associations.
AB  - Autoimmune thyroid disease has been associated with several systemic autoimmune
      disorders. However, limited data are available regarding the prevalence and
      clinical associations of thyroid autoimmunity in antiphospholipid syndrome (APS).
      Seventy-five patients with APS, 75 patients with systemic lupus erythematosus
      (SLE) and 75 healthy controls were tested for the presence of antithyroid
      antibodies (ATAs) (anti-thyroglobulin and anti-thyroid peroxidase [anti-TPO])
      using commercial ELISA. Clinical data were also recorded. Although no significant
      differences in the prevalence of ATAs were detected among APS, SLE patient groups
      and healthy controls, a significant increase of anti-TPO antibodies in patients
      with APS-SLE was found. An increased prevalence of ATAs in APS population with
      ischemic central nervous system (CNS) clinical manifestations was also detected.
      We present novel associations between thyroid autoimmunity and ischemic CNS
      clinical manifestations in the setting of APS.

PMID- 19762386
TI  - A rare opportunistic infection in a woman with systemic lupus erythematosus and
      multiple skin lesions.
AB  - Cutaneous lesions in patients with systemic lupus erythematosus (SLE) represent
      diagnostic challenges. Opportunistic infections should be considered when lupus
      patients are on immunosuppressive therapy and other causes, such as disease
      activity, are less likely to explain the skin lesions. Within the spectrum of
      skin opportunistic infections that might occur in SLE patients, Blastomyces
      dermatitidis should be suspected when acid-fast positive material with no
      bacilliform organisms is seen on Ziehl-Nielsen skin biopsy preparations. In this
      study, we describe one patient with SLE on immunosuppressive therapy, who
      developed cutaneous blastomycosis despite living in a non-endemic area. Because
      of lack of awareness about this association and misinterpretation of the skin
      biopsy results, the diagnosis of atypical mycobacterial infection was initially
      considered. Subsequent proper tissue staining and interpretation revealed the
      correct diagnosis of disseminated cutaneous blastomycosis. This description
      represents the first report of this rare opportunistic skin infection in SLE,
      illustrating the importance of performing correct preparation and elucidation of
      the skin biopsy to avoid misdiagnosis and treatment delay.

PMID- 19762387
TI  - Catastrophic antiphospholipid syndrome in a patient with Down syndrome.
AB  - We report a patient with Down syndrome, under treatment with carbamazepine,
      levopromazine and clonazepam. After urinary infection he developed glans necrosis
      requiring excision of prepuce. Six hours post surgery he presented right-hand
      ischemia followed by arterial and venous thrombosis of the right thoracic
      extremity. Later, he progressed to a compartment syndrome and presented ischemia
      of toes. All the clinical manifestations developed over a week. Anticardiolipin
      (aCL) antibodies, lupus anticoagulant and perinuclear antineutrophil antibodies
      were positive. Anticoagulant and immunosuppressive treatment were initiated.
      Owing to the failure of both treatments, the patient underwent amputation of
      right hand and a toe. Histopathology revealed recent and old thrombosis of medium
      and small-sized vessels without vasculitis. Diagnosis of catastrophic
      antiphospholipid syndrome (CAPS) was made. At present, the patient continues on
      oral anticoagulants, IgG aCL remains positive, and no further episodes of
      thromboses have been observed after 4 years of follow-up. To our knowledge, this
      is the first case of CAPS in a patient with Down syndrome.

PMID- 19762388
TI  - Gelatinous transformation of the bone marrow in systemic lupus erythematosus.
AB  - Gelatinous transformation of the bone marrow is a rare disease characterised by a
      focal marrow hypoplasia, fat atrophy and accumulation of extracellular
      mucopolysaccharides abundant in hyaluronic acid, which is often associated with
      extreme malnutrition and weight loss. There are only two reports describing its
      association with systemic lupus erythematosus (SLE). One described underlying
      diseases in 155 cases of gelatinous transformation of the bone marrow and found
      one case with clinical diagnosis of SLE, but no clinical details were provided.
      The other described three SLE patients with gelatinous transformation of the bone
      marrow; however, two of these were cachectic and one was diagnosed with
      concomitant tuberculosis. We describe one active SLE patient without other
      comorbidities whose pancytopaenia was histologically confirmed as gelatinous
      transformation. The combination of high-dose steroid, intravenous immunoglobulin
      and mycophenolate mofetil improved the peripheral blood cytopaenia and reversed
      the bone marrow abnormalities.

PMID- 19762389
TI  - Prevalence, risk factors and outcome of digital gangrene in 2684 lupus patients.
AB  - The aim of the study is to assess the clinical characteristics, risk factors and
      outcome of patients with systemic lupus erythematosus (SLE) complicated with
      digital gangrene. In all, 2684 consecutive SLE inpatients admitted to Peking
      Union Medical College Hospital from December 1997 to August 2007 were studied.
      Demographic data, clinical features, laboratory findings as well as therapeutic
      regimens were systematically reviewed and a database was established. Cases with
      digital gangrene were identified and followed up. 1) Eighteen patients with SLE
      were complicated with digital gangrene, the average age at event was 33.1 +/-
      11.8 years and the average disease duration was 99.1 +/- 60.1 months. 2) Patients
      with SLE, with long disease duration (> or =4 years), Raynaud's phenomenon and
      elevated serum C-reactive protein (CRP) were more likely to develop digital
      gangrene, P = 0.006, 0.001, and 0.031, respectively, OR = 1.03 (95% CI 1.01,
      1.04), 35.76 (95% CI 4.67, 273.83) and 9.93 (95% CI 1.23, 80.30), respectively.
      3) Fifteen gangrene patients started prednisone > or =1 mg/kg/d, and 18 were
      treated with cyclophosphamide, although 8 cases failed and ultimately received
      digital amputation. Prompt corticosteroid treatment (prednisone > or = mg/kg/d
      started within 3 weeks) decreased the hazard of amputation, P = 0.073, HR = 0.13
      (95% CI 0.01, 1.21). Long disease duration, Raynaud's phenomenon and elevated
      serum CRP were independent predictive factors for SLE to develop digital
      gangrene. Early and aggressive corticosteroid treatment prevented gangrene from
      progression and improved prognosis.

PMID- 19762390
TI  - Splenic volume in systemic lupus erythematosus.

PMID- 19762391
TI  - Idiopathic intracranial hypertension and systemic lupus erythematosus: a case
      report and review of the literature.

PMID- 19762392
TI  - Strong correlation in the serum levels of IgM rheumatoid factor and IgM anti
      Chlamydia pneumoniae antibody.

PMID- 19762393
TI  - Drug-induced lupus: an update on its dermatologic aspects.
AB  - Drug-induced lupus erythematosus (DILE) is defined as an entity characterized by
      clinical manifestations and immunopathological serum findings similar to those of
      idiopathic lupus but which is temporally related to continuous drug exposure and
      resolves after discontinuation of the offending drug. Similar to idiopathic
      lupus, DILE can be divided into systemic lupus erythematosus (SLE), subacute
      cutaneous lupus erythematosus (SCLE) and chronic cutaneous lupus erythematosus
      (CCLE). Based on the literature review and retrospective analysis of our case
      series, we focused on the dermatological aspects of DILE. The cutaneous features
      of drug-induced SLE are protean, including particularly purpura, erythema nodosum
      and photosensitivity as well as the skin lesions characterizing both urticarial
      and necrotizing vasculitis. The typical laboratory profile of systemic DILE
      consists of positive antinuclear antibodies (ANA) and antihistone antibodies, the
      latter being regarded as the serum marker of this subset. The drugs most
      frequently implicated in the development of systemic DILE are hydralazine,
      procainamide, isoniazid and minocycline. Drug-induced SCLE usually presents with
      annular polycyclic or papulosquamous cutaneous manifestations as in the
      idiopathic form, but blisters or targetoid lesions mimicking erythema multiforme
      cannot rarely be associated. The clinical presentation is often generalized, with
      involvement of the lower legs that are usually spared in idiopathic SCLE. ANA and
      anti-Ro/SSA antibodies are usually present, whereas antihistone antibodies are
      uncommonly found. Drugs associated with SCLE include particularly calcium channel
      blockers, angiotensin-converting enzyme inhibitors, thiazide diuretics,
      terbinafine and the recently reported tumour necrosis factor (TNF)-alpha
      antagonists. Drug-induced CCLE is very rarely described in the literature and
      usually refers to fluorouracile agents or TNF-alpha antagonists. The picture is
      characterized by the occurrence of classic discoid lesions, but aspects of lupus
      tumidus can occasionally develop. ANA are demonstrated in around two-thirds of
      the cases. Management of DILE is based on the withdrawal of the offending drug.
      Topical and/or systemic corticosteroids and other immunosuppressive agents should
      be reserved for resistant cases.

PMID- 19762394
TI  - Effects of chronic exposure to DDT and TCDD on disease activity in murine
      systemic lupus erythematosus.
AB  - Oestrogens contribute to the female preponderance of autoimmune diseases such as
      systemic lupus erythematosus (SLE). Environmental xenoestrogens superimposed upon
      endogenous pituitary-gonadal axis may affect the development of autoimmunity.
      This study examined the effects of chronic exposure to xenoestrogens -- o,p'
      dichlorodiphenyltrichloroethane (DDT) and 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD) on disease activity in the New Zealand Black/New Zealand White F1 hybrid
      (B/W) mouse model of SLE. Intact female mice had repeatedly received injections
      of DDT, TCDD or control vehicle since 6 weeks of age. Weight change, albuminuria,
      mortality, relevant immunological and histological parameters were assessed. DDT
      exposure markedly increased the incidence of albuminuria and reduced uterine
      weight but had no measured effects on immunity or mortality in this study. TCDD
      exposed mice had significantly lower incidence of albuminuria, serum anti-DNA
      antibody and total IgG levels, and mortality compared to controls. Also, TCDD
      group had significantly lower thymic and splenic weights, decreased percentages
      of CD4(+)CD8(+) thymocytes and splenic CD4(+) T cells, increased percentage of
      splenic B220(+)sIgM(+) B cells and higher serum interferon gamma concentration.
      Taken together, DDT exposure appeared to accelerate the development of
      albuminuria in lupus-prone mice. TCDD was immunosuppressive to murine SLE.
      Xenoestrogens may have compound- and tissue-specific effects that require further
      elucidation in future work.

PMID- 19762395
TI  - Colour Doppler ultrasound of the ocular circulation in patients with systemic
      lupus erythematosus identifies altered microcirculatory haemodynamics.
AB  - We assessed whether quantitative analysis of Doppler flow velocity waveforms is
      able to identify subclinical microvascular abnormalities in SLE and whether
      eigenvector analysis can detect changes not detectable using the resistive index
      (RI). Fifty-four SLE patients with no conventional cardiovascular risk factors,
      major organ involvement or retinopathy were compared to 32 controls. Flow
      velocity waveforms were obtained from the ophthalmic artery (OA), central retinal
      artery (CRA) and common carotid artery (CA). The waveforms were analysed using
      eigenvector decomposition and compared between groups at each arterial site. The
      RI was also determined. The RI was comparable between groups. In the OA and CRA,
      there were significant differences in the lower frequency sinusoidal components
      (P < 0.05 for each component). No differences were apparent in the CA between
      groups. Eigenvector analysis of Doppler flow waveforms, recorded in proximity of
      the terminal vascular bed, identified altered ocular microvascular haemodynamics
      in SLE. Altered waveform structure could not be identified by changes in RI, the
      traditional measure of downstream vascular resistance. This analytical approach
      to waveform analysis is more sensitive in detecting preclinical microvascular
      abnormalities in SLE. It may hold potential as a useful tool for assessing
      disease activity, response to treatment, and predicting future vascular
      complications.

PMID- 19762397
TI  - Variability and correlates of high sensitivity C-reactive protein in systemic
      lupus erythematosus.
AB  - In the general population, high-sensitivity C-reactive protein (hsCRP), a marker
      of inflammation, is relatively stable over time and independently predicts
      cardiovascular events. Systemic lupus erythematosus (SLE), a chronic inflammatory
      disease, is strongly associated with coronary artery disease (CAD). The objective
      of this study was to determine the variability and correlates of hsCRP in
      patients with SLE. Two cohorts from the University of Toronto Lupus Clinic, one
      with newly diagnosed and the other with prevalent SLE for 4 or more years, were
      selected. HsCRP was measured on serially collected samples, and hsCRP levels were
      ranked according to quartiles of cardiovascular risk. Correlates of hsCRP were
      determined using multivariate regression modelling with analysis of repeated
      measures. Among 58 patients in the inception cohort, over time, 36 (62%) moved
      from one hsCRP risk quartile to another. Among 414 patients in the prevalent
      cohort, 294 (71.0%) moved from one risk quartile to another. In both cohorts,
      within-patient variance comprised the majority of total variance in hsCRP levels.
      In multivariate regression analysis, hsCRP increased with age (P = 0.002),
      postmenopausal status (P = 0.03), smoking (P = 0.007) and presence of infection
      (P = 0.0001) and decreased with use of immunosuppressives (P = 0.02). There is
      marked variability of hsCRP level over time in SLE, regardless of disease
      duration. This variability is due to age and SLE treatment, menopausal status,
      smoking and the occurrence of infection. The variability of hsCRP in SLE casts
      doubt over its usefulness as an independent predictor of CAD risk in this disease
      and potentially in other chronic inflammatory diseases.

PMID- 19762396
TI  - Factors associated with arterial vascular events in PROFILE: a Multiethnic Lupus
      Cohort.
AB  - The objective of this study was to determine the factors associated with the
      occurrence of arterial vascular events in a multiethnic systemic lupus
      erythematosus (SLE) cohort. The PROFILE cohort, comprised SLE patients (n = 1333)
      of defined ethnicity from five different US institutions, was studied to
      determine demographic, clinical and biological variables associated with vascular
      events. An arterial vascular event (first episode) was either a myocardial
      infarction, angina pectoris and/or a vascular procedure for myocardial
      infarction, stroke, claudication and/or evidence of gangrene. Patient
      characteristics were analyzed by univariable and multivariable Cox proportional
      hazards regression analyses. One-hundred twenty-three (9.8%) patients had at
      least one incident arterial event. Age at cohort enrollment (HR = 1.04, 95% CI
      1.03-1.06), smoking (HR = 2.20, 95% CI 1.40-3.46) and the CRP2* C alleles (HR =
      1.91, 95% CI 1.04-3.49) were associated with a shorter time-to-the occurrence of
      arterial vascular events. Some clinical manifestations of disease activity were
      associated with a shorter time-to-occurrence [psychosis (HR = 2.21, 95% CI 1.10
      4.44), seizures (HR = 1.85, 95% CI 1.00-3.24) and anaemia (HR = 1.83, 95% CI 1.02
      3.31)], but others were not [arthritis (HR = 0.32, 95% CI 0.18-0.58)]. In
      conclusion, older patients, especially in the context of a predisposing
      environmental factor (smoking) and severe clinical manifestations, are at higher
      risk of having arterial vascular events. The genetic contribution of the
      variation at the CRP locus was not obscured by demographic or clinical variables.
      Awareness of these factors should lead to more effective management strategies of
      patients at risk for arterial vascular events.

PMID- 19762398
TI  - Association of TNF-alpha gene polymorphisms with systemic lupus erythematosus in
      Taiwanese patients.
AB  - Tumour necrosis factor-alpha (TNF-alpha), an important proinflammatory cytokine,
      exerts a variety of physiological and pathogenic effects that lead to tissue
      destruction. Studies on the association of TNF-alpha genetic polymorphisms with
      systemic lupus erythematosus (SLE) have yielded inconclusive results. We
      investigated the association of TNF-alpha genetic polymorphisms (-1031T/C, 
      863C/A, -857T/C, -308A/G and +489A/G) with SLE in Taiwanese patients and
      controls. Our results indicate that 1) the frequency of the A-allele at -863
      position was significantly higher in SLE patients (odds ratio = 1.46; 95% CI =
      1.02-2.08); 2) the frequency of the A-allele at +489 position was significantly
      higher in SLE patients (odds ratio = 1.79; 95% CI = 1.21-2.65); 3) the AA or GA
      genotype frequencies at +489 position were significantly increased in SLE
      patients (AA genotype: odds ratio = 11.20; 95% CI = 1.36-92.55; GA genotype: odds
      ratio = 1.63; 95% CI = 1.03-2.58); 4) no significant association of TNF-alpha
      haplotypic distributions was observed, except for the haplotypes TCCGA, CACGA and
      CCCGG; and 5) the genotype frequency of the polymorphisms at -1031 was
      significantly different in patients with antinuclear antibodies (P = 0.022). The
      allele and genotype frequencies of the polymorphisms at -863 were not
      significantly different. The genotype frequency of the polymorphisms at -857 was
      significantly different in patients with haematological disorder (P = 0.025). The
      frequency of A allele of the polymorphisms at -308 was significantly increased in
      patients with malar rash (P = 0.033), discoid rash (P = 0.023), photosensitivity
      (P = 0.037), oral ulcers (P = 0.002) and serositis (P = 0.029). The genotype
      frequency of the polymorphisms at +489 was significantly different in patients
      with discoid rash and photosensitivity (data not shown; discoid rash, P = 0.031;
      photosensitivity, P = 0.044). These results suggest that TNF-alpha genetic
      polymorphisms contribute to SLE susceptibility in the Taiwanese population.

PMID- 19762400
TI  - Digital vasculitis in systemic lupus erythematosus: a minor manifestation of
      disease activity?
AB  - The objective of this study is to determine if digital vasculitis (DV), a
      clinical manifestation with a high systemic lupus erythematosus disease activity
      index (SLEDAI) score, is associated with lupus severity. DV and other clinical
      manifestations defined according to the SLEDAI were evaluated in 168 consecutive
      patients with systemic lupus erythematosus (SLE). Two groups were defined
      according to presence (DV+, n = 27) or absence of DV (DV-, n = 141) at the time
      of evaluation. The exclusion criterion was the presence of antiphospholipid
      syndrome (Sapporo's criteria). The two groups were comparable with regard to age
      (P = 0.09), gender (P = 1.00), white race (P = 0.81), and disease duration (P =
      0.78). Compared to the DV- group, the DV+ group had a significantly higher
      frequency of mucocutaneous manifestations (66.7 vs. 39.0%, P = 0.01),
      haematological abnormalities (22.2 vs. 6.4%, P = 0.02) and constitutional
      symptoms (11.1 vs. 0.7%, P = 0.01). Renal and neurological involvements were
      similar in both groups (P = 0.57 and P = 1.00, respectively). The evaluation of
      each SLEDAI parameter confirmed that the DV+ group had higher frequencies of mild
      manifestations, such as new rash (P = 0.02), alopecia (P = 0.02), oral ulcers (P
      = 0.045), fever (P = 0.01) and leucopenia (P = 0.005). In contrast, both groups
      had similarly increased anti-dsDNA (P = 0.78) and decreased complement levels (P
      = 0.29). In conclusion, DV in patients with SLE identifies a subgroup of a mild
      disease. The high 'weighted' index attributed to this alteration in the SLEDAI
      score should therefore be revised.

PMID- 19762399
TI  - Longitudinal expression of type I interferon responsive genes in systemic lupus
      erythematosus.
AB  - Cross-sectional studies of patients with systemic lupus erythematosus (SLE) have
      demonstrated an association between activation of type I interferon (IFN) pathway
      and disease activity. This study examined longitudinal changes in IFN-regulated
      gene expression in peripheral blood using microarrays. A cross-section of 66
      patients from the Autoimmune Biomarkers Collaborative Network SLE archive was
      evaluated. We also examined paired samples from a 15 patient subset collected
      during a period of low disease activity (Baseline) and at a subsequent flare
      event, and baseline scores of 29 patients who maintained low disease activity.
      IFN response (IFNr) scores were calculated from three IFN-regulated genes.
      Overall, higher IFNr scores were associated with increased disease activity.
      However, IFNr scores were not significantly different between the paired Baseline
      and Flare samples. An extended longitudinal analysis in 11 patients indicated
      little change in IFNr scores over time, even during dynamic disease activity. In
      patients with low disease activity, IFNr scores were not different between
      patients who experienced a subsequent flare and those who maintained low disease
      activity. In summary, although higher IFNr scores were associated with greater
      disease activity, IFNr scores of individual patients did not correlate with
      changes in disease severity or flare risk.

PMID- 19762401
TI  - Renal cell apoptosis in human lupus nephritis: a histological study.
AB  - Nuclear autoantigens from apoptotic cells are believed to drive the immunological
      response in systemic lupus erythematosus (SLE). Conflicting data exist as to the
      possible renal origin of apoptotic cells in SLE patients with nephritis. We
      assessed the level of renal cell apoptosis in kidney biopsies from 35 patients
      with lupus nephritis by means of terminal deoxynucleotidyl-transferase (TdT)
      mediated deoxyuridine triphosphate (dUTP)-digoxigenin nick end labeling (TUNEL).
      Five samples of normal kidney tissue served as control specimens. We did not
      observe apoptotic glomerular cells in any of the control or nephritis biopsies.
      Scarce apoptotic tubular cells were seen in 13 of 35 (37%) of the nephritis
      specimens and in two of five (40%) of the control sections. Within the SLE
      cohort, patients with TUNEL-positive tubular cells in their renal biopsies had
      significantly higher activity index scores for tubulointerstitial mononuclear
      cell infiltration than patients without apoptotic tubular cells in their biopsies
      (P = 0.01). Furthermore, the level of tubular cell apoptosis displayed a
      statistically significant, positive correlation with the activity index score for
      mononuclear cell infiltration (r(s) = 0.472, P = 0.004) but not with scores for
      other activity or chronicity index components. These observations indicate that
      the degree of tubular cell apoptosis correlates with the severity of
      tubulointerstitial inflammation in SLE-associated nephritis. However, our
      findings do not suggest that apoptotic renal cells constitute a quantitatively
      important source of auto-antibody-inducing nuclear auto-antigens in human lupus
      nephritis.

PMID- 19762403
TI  - Pulmonary hypertension in polymyositis-dermatomyositis: clinical and hemodynamic
      characteristics and response to vasoactive therapy.
AB  - The increased incidence of pulmonary hypertension and its association with
      decreased survival is well-recognised in patients with systemic sclerosis. This
      association is not widely appreciated in patients with polymyositis
      dermatomyositis. We report clinical and hemodynamic characteristics and response
      to vasoactive therapy in three patients with polymyositis-dermatomyositis and
      pulmonary hypertension and discuss them in light of the available literature.

PMID- 19762402
TI  - The effects of previous hysterectomy on lupus.
AB  - Hysterectomy is one of the most common surgical procedures performed in United
      States, and currently, one in three women in United States has had a hysterectomy
      by the age of 60 years. Systemic lupus erythematosus (SLE) is a common autoimmune
      disease and especially targets women of childbearing age at least 10 times higher
      than men, which reflects the major role of female sex hormones. In this
      retrospective study, we evaluate the potential effects of previous hysterectomy
      in our lupus cohort. Data collected from study subject questionnaires were
      obtained from the Lupus Family Registry and Repository (LFRR) at the Oklahoma
      Medical Research Foundation. Hysterectomy data were available from 3389 subjects.
      SLE patients with a positive history of hysterectomy have been selected and
      compared with matched lupus patients with a negative history of hysterectomy and
      healthy controls. Association analyses were performed, and the P values and
      adjusted odds ratios (ORs) were calculated. SLE patients with a negative history
      of hysterectomy more likely had kidney nephritis or positive anti-dsDNA than age
      matched SLE patients with a history of hysterectomy before disease onset. This
      effect was independent of ethnicity with an OR of 6.66 (95% CI = 3.09-14.38, P =
      1.00 x 10(-8)) in European patients and 2.74 (95% CI = 1.43-5.25, P = 0.001) in
      African-Americans. SLE patients with a positive history of hysterectomy before
      disease onset also had a later age of disease onset (P = 0.0001) after adjustment
      for age and race. Our findings support the notion that the influence of female
      sex hormones in SLE and various clinical findings are tremendous and that
      surgical menopause such as this could significantly affect the outcome of disease
      and clinical manifestations.

PMID- 19762404
TI  - Isolated elevation of IgA anti-beta2glycoprotein I antibodies with manifestations
      of antiphospholipid syndrome: a case series of five patients.
AB  - Current diagnostic classification criteria recommend elevated titres of anti
      cardiolipin (aCL) and/or anti-beta(2)GPI antibody by ELISA IgG or IgM and/or
      lupus anticoagulant (LA) to confirm antiphospholipid syndrome (APS). Although IgA
      aPL antibodies have been shown to be pathogenic in animal models of APS, their
      clinical significance has remained elusive. We report four cases of exclusive IgA
      anti-beta(2)GPI antibody sero-positivity with concomitant clinical manifestations
      associated with APS. Four of the five patients were LA negative. 1) Thirty-eight
      year-old African-American female with SLE presented with resolving digital
      ulcers. Serum IgA anti-beta(2)GPI antibody titres were 118.5 SAU (normal range: 0
      20 SAU). 2) Twenty-seven-year-old African-American woman with SLE was evaluated
      for recent onset of severe headaches, unresponsive to analgesics and anti
      migraine medications. MRI of the brain revealed hyper-intensities in the white
      matter in the frontal lobes. Serum IgA anti-beta(2)GPI antibody titres were 29.1
      Standard A Units (SAU). 3) Thirty-two-year-old Hispanic female with history of
      two unexplained miscarriages and negative serologies for SLE. Serum IgA anti
      beta(2)GPI antibody titres were 102.0 SAU. 4) Twenty-five-year-old white female
      with history of recent unexplained miscarriage in the 11th week of gestation and
      associated complaints of numbness and tingling in her hands. Her IgA anti
      beta(2)GPI antibody titre was 62.0 SAU. 5) Twenty-five-year-old African-American
      woman with SLE, positive for anti-Ro antibodies with a history of ischemic
      fingers, a pregnancy loss and recent pregnancy complicated due to pre-eclampsia.
      Her LA was positive and her IgA anti-beta(2)GPI antibody titer was 186.0 SAU.
      This case series supports that elevated IgA anti-beta(2)GPI antibody titres may
      identify additional patients who have clinical features of APS but who do not
      meet current diagnostic criteria.

PMID- 19762405
TI  - Gigantomastia and autoimmunity: a case report.
AB  - Gigantomastia is a rare breast condition characterised by diffuse, rapid, and
      excessive breast hypertrophy that can result in symptoms ranging from pain to
      necrosis and sepsis. It typically occurs in the setting of marked hormonal
      changes such as puberty and pregnancy. Rarely, gigantomastia has been reported to
      develop in the setting of an autoimmune illness. We present a case of
      gigantomastia developing in a patient with systemic lupus erythematosus, who was
      treated with methotrexate and bilateral mammoplasty.

PMID- 19762406
TI  - Metabolic syndrome in Argentinean patients with systemic lupus erythematosus.
AB  - The objective was to determine the prevalence of the metabolic syndrome (MS) in
      patients with systemic lupus erythematosus (SLE) in Argentina, to assess the
      factors associated to it, and to compare the results with a control group with
      non-inflammatory disorders. The study included 147 patients with SLE and 119
      controls. MS was defined according to criteria by the American Heart
      Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) Scientific
      Statement. Demographic characteristics, Systemic Lupus Erythematosus Disease
      Activity Index (SLEDAI) and Systemic Lupus International Collaborating
      Clinics/ACR Damage Index (SDI) were assessed as well as administration, maximum
      dose and cumulative dose of prednisone and hydroxychloroquine (HCQ). MS
      prevalence was 28.6% (CI 95%: 21.4-36.6) in patients with SLE and 16% in controls
      (P = 0.0019). Patients with SLE presented higher arterial hypertension frequency
      compared with controls (43 vs 25%, P = 0.007). When comparing lupus patients with
      MS (n = 41) and without MS (n = 106), no significant differences were observed
      regarding duration of the disease, SLEDAI or cumulative prednisone dose.
      Cumulative damage was associated independently with MS (OR 1.98; P = 0.021),
      whereas HCQ use was found to be protective (OR 0.13; P = 0.015). Patients with
      lupus presented higher MS prevalence than controls with non-inflammatory
      disorders, and occurrence of arterial hypertension was also higher. MS was
      associated with cumulative damage; the use of HCQ showed to be protective against
      presence of MS.

PMID- 19762407
TI  - Supraspinatus tendon rupture in lupus: a rarity.

PMID- 19762408
TI  - Microangiopathic haemolytic anaemias in systemic lupus erythematosus.

PMID- 19762410
TI  - Dissociative disorders in a psychiatric institute in India--a selected review and
      patterns over a decade.
AB  - BACKGROUND: The prevalence--and type--of dissociative disorders is considered to
      vary across cultures and over time. AIMS: The aim of the study was to examine
      patterns of dissociative disorders among subjects attending psychiatric services
      over a period of 10 years. METHODS: The sample consisted of both inpatients and
      outpatients attending a psychiatric hospital between 1999 and 2008. Information
      of those subjects diagnosed to have dissociative disorders was reviewed. A semi
      structured proforma was used to collect information about demographic details and
      diagnosis. RESULTS: A total of 893 patients had been diagnosed with dissociative
      disorder over the past decade: 591 (66%) were outpatients and 302 (34%) were
      inpatients. The proportion of patients diagnosed with dissociative disorders
      ranged between 1.5 and 15.0 per 1,000 for outpatients and between 1.5 and 11.6
      per 1,000 for inpatients. The majority of patients were diagnosed with
      dissociative motor disorder (43.3% outpatients, 37.7% inpatients), followed by
      dissociative convulsions (23% outpatients, 27.8% inpatients). Female
      preponderance was seen across all sub-types of dissociative disorder except
      dissociative fugue. CONCLUSIONS: Dissociative disorders are still commonly
      diagnosed in both inpatient and outpatient settings. Dissociative motor disorders
      and dissociative convulsions are the most common disorders. Unlike in the West,
      dissociative identity disorders were rarely diagnosed; instead, possession states
      were commonly seen in the Indian population, indicating cross-cultural disparity.

PMID- 19762412
TI  - Unrecognised scurvy.

PMID- 19762413
TI  - Should we screen for coeliac disease? Yes.

PMID- 19762414
TI  - Should we screen for coeliac disease? No.

PMID- 19762416
TI  - Understanding why some ethnic minority patients evaluate medical care more
      negatively than white patients: a cross sectional analysis of a routine patient
      survey in English general practices.
AB  - OBJECTIVE: To examine why patients from ethnic minorities give poorer evaluations
      of primary health care than white patients. DESIGN: Cross sectional analysis of
      patient surveys collected in general practice. SETTING: 1098 English general
      practices that undertook a routine survey of patients using the General Practice
      Assessment Questionnaire between April 2005 and March 2006. PARTICIPANTS: 188,572
      survey respondents, 95.8% of whom identified themselves as "white," "black/black
      British," "Asian/Asian British," or "Chinese." Analyses were restricted to
      between 133,441 (71%) and 147,686 (78%) respondents with complete data on
      relevant variables. MAIN OUTCOME MEASURES: Patient evaluations of waiting times
      for general practitioner appointments, time spent waiting in surgeries for
      consultations to start, and continuity of care. RESULTS: All aspects of care were
      rated substantially lower by respondents from the three ethnic minority groups
      than by white patients. Poorer evaluations of time spent waiting for
      consultations to begin (rated lowest by Asian patients) and continuity of care
      (rated lowest by Chinese patients) appeared to reflect worse reported experiences
      by ethnic minority groups. Substantial differences between white and ethnic
      minority patients' ratings of appointment waiting times persisted, however, even
      after adjusting for the actual time patients reported waiting. This effect
      disappeared for Chinese and black respondents after adjusting for evaluations of
      reception staff and doctors' communication skills, but Asian patients' ratings
      remained considerably lower than those of white respondents. CONCLUSIONS:
      Important differences in assessments of care exist in different ethnic minority
      groups. Some negative evaluations may reflect communication issues. Among Asian
      patients, lower ratings of waiting times for appointments may also reflect
      different expectations of care. Adjusting survey results for ethnicity may be
      justified when comparing healthcare providers; however, health services also have
      a responsibility to meet legitimate patient expectations.

PMID- 19762417
TI  - Life expectancy in relation to cardiovascular risk factors: 38 year follow-up of
      19,000 men in the Whitehall study.
AB  - OBJECTIVE: To assess life expectancy in relation to cardiovascular risk factors
      recorded in middle age. DESIGN: Prospective cohort study. SETTING: Men employed
      in the civil service in London, England. PARTICIPANTS: 18 863 men examined at
      entry in 1967-70 and followed for 38 years, of whom 13,501 died and 4811 were re
      examined in 1997. MAIN OUTCOME MEASURES: Life expectancy estimated in relation to
      fifths and dichotomous categories of risk factors (smoking, "low" or "high" blood
      pressure (>or=140 mm Hg), and "low" or "high" cholesterol (>or=5 mmol/l)), and a
      risk score from these risk factors. RESULTS: At entry, 42% of the men were
      current smokers, 39% had high blood pressure, and 51% had high cholesterol. At
      the re-examination, about two thirds of the previously "current" smokers had quit
      smoking shortly after entry and the mean differences in levels of those with high
      and low levels of blood pressure and cholesterol were attenuated by two thirds.
      Compared with men without any baseline risk factors, the presence of all three
      risk factors at entry was associated with a 10 year shorter life expectancy from
      age 50 (23.7 v 33.3 years). Compared with men in the lowest 5% of a risk score
      based on smoking, diabetes, employment grade, and continuous levels of blood
      pressure, cholesterol concentration, and body mass index (BMI), men in the
      highest 5% had a 15 year shorter life expectancy from age 50 (20.2 v 35.4 years).
      CONCLUSION: Despite substantial changes in these risk factors over time, baseline
      differences in risk factors were associated with 10 to 15 year shorter life
      expectancy from age 50.

PMID- 19762418
TI  - Ethnic minorities and their perceptions of the quality of primary care.

PMID- 19762419
TI  - Monitoring of atrial fibrillation burden after surgical ablation: relevancy of
      end-point criteria after radiofrequency ablation treatment of patients with lone
      atrial fibrillation.
AB  - Studies have shown that continuous rhythm monitoring enables the detection of
      significantly more atrial fibrillation (AF) episodes than routine follow-up of
      patients, i.e. based on perception of symptoms or on 24-48 h Holter monitoring.
      The positive outcome of radiofrequency ablation (RFA) may be easily
      overestimated, especially in patients with paroxysmal AF. Thirty-three
      consecutive patients, aged 59.4+/-8.9 years (range 38-75 years) participated in
      this study. All patients had documented AF episodes with an AF duration of 9.4+/
      7.1 years (range 1.5-25 years). A new monitoring device, the AF-Alarm was used to
      more accurately assess the outcome after surgical isolation of pulmonary veins.
      The AF-Alarm was applied for a duration of 128+/-42.5 h (range 49-191 h) during a
      period of 8-15 days. The success rate was 87% based on serial electrocardiograms
      (ECGs) and 24-48 h Holter monitoring during regular outpatient visits.
      Combination of ECG, Holter and AF-Alarm data yielded a significantly lower
      success rate, i.e. at the latest follow-up 69% of the patients were free from AF
      after surgical ablation (P<0.05). Furthermore, the AF-Alarm device demonstrated a
      dissociation between symptoms and atrial arrhythmic events and confirmed the
      occurrence of asymptomatic AF episodes. The most important limitation of the AF
      Alarm device was noise detection with oversensing and inappropriate detection of
      non-existing AF episodes in 9% of patients. Long-term follow-up of the patients
      seems to be essential as success rates of the initial ablation procedure might
      vary over time. External recorders like the AF-Alarm may be used as an additional
      tool to document symptomatic and asymptomatic episodes of atrial arrhythmias in
      the outpatient setting.

PMID- 19762420
TI  - Peripheral venous embolized intracardiac foreign body.
AB  - Embolized intracardiac foreign bodies have been previously described in the
      literature. Those related to iatrogenic procedures, such as catheters and
      pacemaker electrodes, are the most common. However, traumatic embolization of a
      metal foreign body is scantily described. We report a case of a peripheral venous
      embolized intracardiac metal foreign body after traumatic elbow injury. A review
      of the literature is therefore performed. Intracardiac foreign body removal must
      be considered when its diameter exceeds 5 mm, its shape is irregular or when
      symptomatic.

PMID- 19762421
TI  - Spindle alignment is achieved without rotation after the first cell cycle in
      Drosophila embryonic neuroblasts.
AB  - Spindle alignment along the apicobasal polarity axis is mandatory for proper self
      renewing asymmetric division in Drosophila neuroblasts (NBs). In embryonic NBs,
      spindles have been reported to assemble orthogonally to the polarity axis and
      later rotate to align with it. In larval NBs, spindles assemble directly aligned
      with the axis owing to the differential spatiotemporal control of the microtubule
      organising activity of their centrosomes. We have recorded embryonic NBs that
      express centrosome and microtubule reporters, from delamination up to the fourth
      cell cycle, by two-photon confocal microscopy, and have found that the switch
      between these two spindle orientation modes occurs in the second cell cycle of
      the NB, the first that follows delamination. Therefore, predetermined spindle
      orientation is not restricted to larval NBs. On the contrary, it actually applies
      to all but the first cell cycle of embryonic NBs.

PMID- 19762422
TI  - Convergent extension movements in growth plate chondrocytes require gpi-anchored
      cell surface proteins.
AB  - Proteins that are localized to the cell surface via glycosylphosphatidylinositol
      (gpi) anchors have been proposed to regulate cell signaling and cell adhesion
      events involved in tissue patterning. Conditional deletion of Piga, which encodes
      the catalytic subunit of an essential enzyme in the gpi-biosynthetic pathway, in
      the lateral plate mesoderm results in normally patterned limbs that display
      chondrodysplasia. Analysis of mutant and mosaic Piga cartilage revealed two
      independent cell autonomous defects. First, loss of Piga function interferes with
      signal reception by chondrocytes as evidenced by delayed maturation. Second, the
      proliferative chondrocytes, although present, fail to flatten and arrange into
      columns. We present evidence that the abnormal organization of mutant
      proliferative chondrocytes results from errors in cell intercalation.
      Collectively, our data suggest that the distinct morphological features of the
      proliferative chondrocytes result from a convergent extension-like process that
      is regulated independently of chondrocyte maturation.

PMID- 19762423
TI  - A gene network for long-day flowering activates RFT1 encoding a mobile flowering
      signal in rice.
AB  - Although some genes that encode sensory or regulatory elements for photoperiodic
      flowering are conserved between the long-day (LD) plant Arabidopsis thaliana and
      the short-day (SD) plant rice, the gene networks that control rice flowering, and
      particularly flowering under LD conditions, are not well understood. We show here
      that RICE FLOWERING LOCUS T 1 (RFT1), the closest homolog to Heading date 3a
      (Hd3a), is a major floral activator under LD conditions. An RFT1:GFP fusion
      protein localized in the shoot apical meristem (SAM) under LD conditions,
      suggesting that RFT1 is a florigen gene in rice. Furthermore, mutants in
      OsMADS50, a rice ortholog of Arabidopsis SUPPRESOR OF OVEREXPRESSION OF CONSTANS
      1 (SOC1) did not flower up to 300 days after sowing under LD conditions,
      indicating that OsMADS50, which acts upstream of RFT1, promotes flowering under
      LD conditions. We propose that both positive (OsMADS50 and Ehd1) and negative
      (Hd1, phyB and Ghd7) regulators of RFT1 form a gene network that regulates LD
      flowering in rice. Among these regulators, Ehd1, a rice-specific floral inducer,
      integrates multiple pathways to regulate RFT1, leading to flowering under
      appropriate photoperiod conditions. A rice ortholog of Arabidopsis APETALA1,
      OsMADS14, was expressed in the floral meristem in wild-type but not in RFT1 RNAi
      plants, suggesting that OsMADS14 is activated by RFT1 protein in the SAM after
      the transition to flowering. We have thus exposed a network of genes that
      regulate LD flowering in rice.

PMID- 19762424
TI  - Lineage-specific cell death in postembryonic brain development of Drosophila.
AB  - The Drosophila central brain is composed of thousands of neurons that derive from
      approximately 100 neuroblasts per hemisphere. Functional circuits in the brain
      require precise neuronal wiring and tight control of neuronal numbers. How this
      accurate control of neuronal numbers is achieved during neural development is
      largely unclear. Specifically, the role of programmed cell death in control of
      cell numbers has not been studied in the central brain neuroblast lineages. Here,
      we focus on four postembryonic neuroblast lineages in the central brain
      identified on the basis that they express the homeobox gene engrailed (en). For
      each lineage, we determine the total number of adult-specific neurons generated
      as well as number and pattern of en-expressing cells. We then demonstrate that
      programmed cell death has a pronounced effect on the number of cells in the four
      lineages; approximately half of the immature adult-specific neurons in three of
      the four lineages are eliminated by cell death during postembryonic development.
      Moreover, we show that programmed cell death selectively affects en-positive
      versus en-negative cells in a lineage-specific manner and, thus, controls the
      relative number of en-expressing neurons in each lineage. Furthermore, we provide
      evidence that Notch signaling is involved in the regulation of en expression.
      Based on our findings, we conclude that lineage-specific programmed cell death
      plays a prominent role in the generation of neuronal number and lineage diversity
      in the Drosophila brain.

PMID- 19762425
TI  - Akt-dependent Pp2a activity is required for epidermal barrier formation during
      late embryonic development.
AB  - Acquisition of epidermal barrier function occurs late in mouse gestation. Several
      days before birth a wave of barrier acquisition sweeps across murine fetal skin,
      converging on dorsal and ventral midlines. We investigated the molecular pathways
      active during epidermal barrier formation. Akt signaling increased as the barrier
      wave crossed epidermis and Jun was transiently dephosphorylated. Inhibitor
      experiments on embryonic explants showed that the dephosphorylation of Jun was
      dependent on both Akt and protein phosphatase 2A (Pp2a). Inhibition of Pp2a and
      Akt signaling also caused defects in epidermal barrier formation. These data are
      compatible with a model for developmental barrier acquisition mediated by Pp2a
      regulation of Jun dephosphorylation, downstream of Akt signaling. Support for
      this model was provided by siRNA-mediated knockdown of Ppp2r2a (Pr55alpha or
      B55alpha), a regulatory subunit of Pp2a expressed in an Akt-dependent manner in
      epidermis during barrier formation. Ppp2r2a reduction caused significant increase
      in Jun phosphorylation and interfered with the acquisition of barrier function,
      with barrier acquisition being restored by inhibition of Jun phosphorylation. Our
      data provide strong evidence that Ppp2r2a is a regulatory subunit of Pp2a that
      targets this phosphatase to Jun, and that Pp2a action is necessary for barrier
      formation. We therefore describe a novel Akt-dependent Pp2a activity that acts at
      least partly through Jun to affect initial barrier formation during late
      embryonic epidermal development.

PMID- 19762426
TI  - H19 acts as a trans regulator of the imprinted gene network controlling growth in
      mice.
AB  - The imprinted H19 gene produces a non-coding RNA of unknown function. Mice
      lacking H19 show an overgrowth phenotype, due to a cis effect of the H19 locus on
      the adjacent Igf2 gene. To explore the function of the RNA itself, we produced
      transgenic mice overexpressing H19. We observed postnatal growth reduction in two
      independent transgenic lines and detected a decrease of Igf2 expression in
      embryos. An extensive analysis of several other genes from the newly described
      imprinted gene network (IGN) was performed in both loss- and gain-of-function
      animals. We found that H19 deletion leads to the upregulation of several genes of
      the IGN. This overexpression is restored to the wild-type level by transgenic
      expression of H19. We therefore propose that the H19 gene participates as a trans
      regulator in the fine-tuning of this IGN in the mouse embryo. This is the first
      in vivo evidence of a functional role for the H19 RNA. Our results also bring
      further experimental evidence for the existence of the IGN and open new
      perspectives in the comprehension of the role of genomic imprinting in embryonic
      growth and in human imprinting pathologies.

PMID- 19762427
TI  - Developmental switch in NF-kappaB signalling required for neurite growth.
AB  - For a given cell type, particular extracellular signals generate characteristic
      patterns of activity in intracellular signalling networks that lead to
      distinctive cell-type specific responses. Here, we report the first known
      occurrence of a developmental switch in the intracellular signalling network
      required for an identical cellular response to the same extracellular signal in
      the same cell type. We show that although NF-kappaB signalling is required for
      BDNF-promoted neurite growth from both foetal and postnatal mouse sensory
      neurons, there is a developmental switch between these stages in the NF-kappaB
      activation mechanism and the phosphorylation status of the p65 NF-kappaB subunit
      required for neurite growth. Shortly before birth, BDNF activates NF-kappaB by an
      atypical mechanism that involves tyrosine phosphorylation of IkappaBalpha by Src
      family kinases, and dephosphorylates p65 at serine 536. Immediately after birth,
      BDNF-independent constitutive activation of NF-kappaB signalling by serine
      phosphorylation of IkappaBalpha and constitutive dephosphorylation of p65 at
      serine 536 are required for BDNF-promoted neurite growth. This abrupt
      developmental switch in NF-kappaB signalling in a highly differentiated cell type
      illustrates an unsuspected plasticity in signalling networks in the generation of
      identical cellular responses to the same extracellular signal.

PMID- 19762429
TI  - Middle ear implantable hearing devices: an overview.
AB  - Hearing loss affects approximately 30 million people in the United States. It has
      been estimated that only approximately 20% of people with hearing loss
      significant enough to warrant amplification actually seek assistance for
      amplification. A significant interest in middle ear implants has emerged over the
      years to facilitate patients who are noncompliant with conventional hearing
      aides, do not receive significant benefit from conventional aides, or are not
      candidates for cochlear implants. From the initial studies in the 1930s, the
      technology has greatly evolved over the years with a wide array of devices and
      mechanisms employed in the development of implantable middle ear hearing devices.
      Currently, these devices are generally available in two broad categories:
      partially or totally implantable using either piezoelectric or electromagnetic
      systems. The authors present an up-to-date overview of the major implantable
      middle ear devices. Although the current devices are largely in their infancy,
      indications for middle ear implants are ever evolving as promising studies show
      good results. The totally implantable devices provide the user freedom from the
      social and practical difficulties of using conventional amplification.

PMID- 19762428
TI  - Auditory midbrain implant: a review.
AB  - The auditory midbrain implant (AMI) is a new hearing prosthesis designed for
      stimulation of the inferior colliculus in deaf patients who cannot sufficiently
      benefit from cochlear implants. The authors have begun clinical trials in which
      five patients have been implanted with a single shank AMI array (20 electrodes).
      The goal of this review is to summarize the development and research that has led
      to the translation of the AMI from a concept into the first patients. This study
      presents the rationale and design concept for the AMI as well a summary of the
      animal safety and feasibility studies that were required for clinical approval.
      The authors also present the initial surgical, psychophysical, and speech results
      from the first three implanted patients. Overall, the results have been
      encouraging in terms of the safety and functionality of the implant. All patients
      obtain improvements in hearing capabilities on a daily basis. However,
      performance varies dramatically across patients depending on the implant location
      within the midbrain with the best performer still not able to achieve open set
      speech perception without lip-reading cues. Stimulation of the auditory midbrain
      provides a wide range of level, spectral, and temporal cues, all of which are
      important for speech understanding, but they do not appear to sufficiently fuse
      together to enable open set speech perception with the currently used stimulation
      strategies. Finally, several issues and hypotheses for why current patients
      obtain limited speech perception along with several feasible solutions for
      improving AMI implementation are presented.

PMID- 19762431
TI  - Rottlerin stimulates apoptosis in pancreatic cancer cells through interactions
      with proteins of the Bcl-2 family.
AB  - Rottlerin is a polyphenolic compound derived from Mallotus philipinensis. In the
      present study, we show that rottlerin decreased tumor size and stimulated
      apoptosis in an orthotopic model of pancreatic cancer with no effect on normal
      tissues in vivo. Rottlerin also induced apoptosis in pancreatic cancer (PaCa)
      cell lines by interacting with mitochondria and stimulating cytochrome c release.
      Immunoprecipitation results indicated that rottlerin disrupts complexes of
      prosurvival Bcl-xL with Bim and Puma. Furthermore, siRNA knockdown showed that
      Bim and Puma are necessary for rottlerin to stimulate apoptosis. We also showed
      that rottlerin and Bcl-2 and Bcl-xL inhibitor BH3I-2' stimulate apoptosis through
      a common mechanism. They both directly interact with mitochondria, causing
      increased cytochrome c release and mitochondrial depolarization, and both
      decrease sequestration of BH3-only proteins by Bcl-xL. However, the effects of
      rottlerin and BH3I-2' on the complex formation between Bcl-xL and BH3-only
      proteins are different. BH3I-2' disrupts complexes of Bcl-xL with Bad but not
      with Bim or Puma, whereas rottlerin had no effect on the Bcl-xL interaction with
      Bad. Also BH3I-2', but not rottlerin, required Bad to stimulate apoptosis. In
      conclusion, our results demonstrate that rottlerin has a potent proapoptotic and
      antitumor activity in pancreatic cancer, which is mediated by disrupting the
      interaction between prosurvival Bcl-2 proteins and proapoptotic BH3-only
      proteins. Thus rottlerin represents a promising novel agent for pancreatic cancer
      treatment.

PMID- 19762432
TI  - The human proton-coupled folate transporter (hPCFT): modulation of intestinal
      expression and function by drugs.
AB  - Folic acid is a vitamin essential for thymidylate and purine synthesis. The human
      proton-coupled folate transporter (hPCFT) has recently been identified as a pH
      dependent folic acid transporter, and mutations in this transporter have been
      linked to hereditary folic acid malabsorption. In this study, we assessed hPCFT
      mediated transport activity in vitro, intersubject variability of intestinal
      expression in relation to blood folates, and the relationship of proton-pump
      inhibitor (PPI) therapy on hPCFT expression in vivo. We created a Madin-Darby
      canine kidney strain II (MDCKII) cell line stably expressing hPCFT to evaluate
      its drug substrates and inhibitors. Intestinal pinch biopsies (duodenum, ileum,
      colon) were collected from patients undergoing routine endoscopy procedures, and
      expressed levels of hPCFT were determined by RT-PCR. When assessed using MDCKII
      hPCFT cells, folic acid and methotrexate were found to be high-affinity hPCFT
      substrates. Sulfasalazine and pyrimethamine were noted to inhibit hPCFT activity
      with Ki values of 42.3 and 161.7 micromol/l, respectively. hPCFT was localized to
      the brush-border membrane of enterocytes with highest expression in the duodenum
      and reduced levels in the ileum and colon. When we assessed hPCFT expression in a
      subset of patients who were receiving PPI therapy, a near 50% reduction in
      duodenal hPCFT mRNA expression was noted. These results suggest that hPCFT
      transporter activity can be modulated by many drugs in clinical use, and
      expression of this transporter in the gastrointestinal tract is higher in the
      duodenum than more distal sites (duodenum > ileum > colon). Importantly, we note
      that PPI drug use appears to be associated with reduced hPCFT expression in vivo.

PMID- 19762436
TI  - Influence of type IV pilus retraction on the architecture of the Neisseria
      gonorrhoeae-infected cell cortex.
AB  - Early in infection, Neisseria gonorrhoeae can be observed to attach to the
      epithelial cell surface as microcolonies and induce dramatic changes to the host
      cell cortex. We tested the hypothesis that type IV pili (Tfp) retraction plays a
      role in the ultrastructure of both the host cell cortex and the bacterial
      microcolony. Using serial ultrathin sectioning, transmission electron microscopy
      and 3D reconstruction of serial 2D images, we have obtained what we believe to be
      the first 3D reconstructions of the N. gonorrhoeae-host cell interface, and
      determined the architecture of infected cell microvilli as well as the attached
      microcolony. Tfp connect both wild-type (wt) and Tfp retraction-deficient
      bacteria with each other, and with the host cell membrane. Tfp fibres and
      microvilli form a lattice in the wt microcolony and at its periphery. Wt
      microcolonies induce microvilli formation and increases of surface area, leading
      to an approximately ninefold increase in the surface area of the host cell
      membrane at the site of attachment. In contrast, Tfp retraction-deficient
      microcolonies do not affect these parameters. Wt microcolonies had a symmetrical,
      dome-shaped structure with a circular 'footprint', while Tfp retraction-deficient
      microcolonies were notably less symmetrical. These findings support a major role
      for Tfp retraction in microvilli and microcolony architecture. They are
      consistent with the biophysical attributes of Tfp and the effects of Tfp
      retraction on epithelial cell signalling.

PMID- 19762437
TI  - Development of a non-invasive murine infection model for acute otitis media.
AB  - Otitis media (OM) is one of the most frequent diseases in childhood, and
      Streptococcus pneumoniae is among the main causative bacterial agents. Since
      current experimental models used to study the bacterial pathogenesis of OM have
      several limitations, such as the invasiveness of the experimental procedures, we
      developed a non-invasive murine OM model. In our model, adapted from a previously
      developed rat OM model, a pressure cabin is used in which a 40 kPa pressure
      increase is applied to translocate pneumococci from the nasopharyngeal cavity
      into both mouse middle ears. Wild-type pneumococci were found to persist in the
      middle ear cavity for 144 h after infection, with a maximum bacterial load at 96
      h. Inflammation was confirmed at 96 and 144 h post-infection by IL-1beta and TNF
      alpha cytokine analysis and histopathology. Subsequently, we investigated the
      contribution of two surface-associated pneumococcal proteins, the streptococcal
      lipoprotein rotamase A (SlrA) and the putative proteinase maturation protein A
      (PpmA), to experimental OM in our model. Pneumococci lacking the slrA gene, but
      not those lacking the ppmA gene, were significantly reduced in virulence in the
      OM model. Importantly, pneumococci lacking both genes were significantly more
      attenuated than the DeltaslrA single mutant. This additive effect suggests that
      SlrA and PpmA exert complementary functions during experimental OM. In
      conclusion, we have developed a highly reproducible and non-invasive murine
      infection model for pneumococcal OM using a pressure cabin, which is very
      suitable to study pneumococcal pathogenesis and virulence in vivo.

PMID- 19762438
TI  - Differential expression of Salmonella type III secretion system factors InvJ,
      PrgJ, SipC, SipD, SopA and SopB in cultures and in mice.
AB  - The type III secretion system (T3SS) encoded by Salmonella pathogenicity island 1
      (SPI-1) is important for the invasion of epithelial cells during development of
      Salmonella-associated enterocolitis. It has been suggested that the level and
      timing of the expression of the SPI-1 T3SS proteins and effectors dictate the
      consequences of bacterial infection and pathogenesis. However, the expression of
      these proteins has not been extensively studied in vivo, especially during the
      later stages of salmonellosis when the infection is established. We have
      constructed recombinant Salmonella strains that contain a FLAG epitope inserted
      in-frame to genes invJ, prgJ, sipC, sipD, sopA and sopB, and investigated the
      expression of the tagged proteins both in vitro and in vivo during murine
      salmonellosis. Mice were inoculated intraperitoneally or intragastrically with
      the tagged Salmonella strains. At different time points post-infection, bacteria
      were recovered from various organs, and the expression of the tagged proteins was
      determined. Our results provide direct evidence that PrgJ and SipD are expressed
      in Salmonella colonizing the liver and ileum of infected animals at both the
      early and late stages of infection. Furthermore, our study has shown that the
      InvJ protein is expressed preferentially in Salmonella colonizing the ileum but
      not the liver, while SipC is expressed preferentially in Salmonella colonizing
      the liver but not the ileum. Thus, Salmonella appears to express different SPI-1
      proteins and effectors when colonizing specific tissues. Our results suggest that
      differential expression of these proteins may be important for tissue-specific
      aspects of bacterial pathogenesis such as gastroenterititis in the ileum and
      systemic infection in the liver.

PMID- 19762439
TI  - Deletion of Mid1, a putative stretch-activated calcium channel in Claviceps
      purpurea, affects vegetative growth, cell wall synthesis and virulence.
AB  - The putative Claviceps purpurea homologue of the Saccharomyces cerevisiae stretch
      activated calcium ion channel Mid1 was investigated for its role in vegetative
      growth, differentiation and pathogenicity on rye (Secale cereale). Gene
      replacement mutants of Cl. purpurea mid1 were not affected in polar growth and
      branching in axenic culture but showed a significantly reduced growth rate. The
      growth defect could not be complemented by Ca(2+) supplementation, in contrast to
      mid1 mutants in yeast, but the altered sensitivity of the mutants to changes in
      external and internal Ca(2+) concentrations indicates some role of Mid1 in Ca(2+)
      homeostasis. The major effect of mid1 deletion, however, was the complete loss of
      virulence: infected rye plants showed no disease symptoms at all. Detailed
      analyses of in vitro-infected rye ovaries demonstrated that the Deltamid1 mutants
      had multiple apical branches and were unable to infect the host tissue,
      suggesting that Mid1 is essential for generating the necessary mechanical force
      for penetration. This is believed to be the first report of an essential role for
      a Mid1 homologue in the virulence of a plant-pathogenic fungus.

PMID- 19762440
TI  - A tyrosine O-prenyltransferase catalyses the first pathway-specific step in the
      biosynthesis of sirodesmin PL.
AB  - A putative prenyltransferase gene sirD has been identified in the gene cluster
      encoding the biosynthesis of the phytotoxin sirodesmin PL in Leptosphaeria
      maculans. The gene product was found to comprise 449 aa, with a molecular mass of
      51 kDa. In this study, the coding region of sirD was amplified by PCR from cDNA,
      cloned into pQE70, and overexpressed in Escherichia coli. The overproduced
      protein was purified to apparent homogeneity, and characterized biochemically.
      The dimeric recombinant SirD was found to catalyse the O-prenylation of L-Tyr in
      the presence of dimethylallyl diphosphate; this was demonstrated unequivocally by
      isolation and structural elucidation of the enzymic product. Therefore, SirD
      catalyses the first pathway-specific step in the biosynthesis of sirodesmin PL.
      K(m) values for L-Tyr and dimethylallyl diphosphate were determined as 0.13 and
      0.17 mM, respectively. Interestingly, SirD was found to share significant
      sequence similarity with indole prenyltransferases, which catalyse prenyl
      transfer reactions onto different positions of indole rings. In contrast to
      indole prenyltransferases, which accept indole derivatives, but not Tyr or
      structures derived thereof, as substrates, SirD also prenylated L-Trp, resulting
      in the formation of 7-dimethylallyltryptophan. A K(m) value of 0.23 mM was
      determined for L-Trp. Turnover numbers of 1.0 and 0.06 S(-1) were calculated for
      L-Tyr and L-Trp, respectively.

PMID- 19762441
TI  - The novel polysaccharide deacetylase homologue Pdi contributes to virulence of
      the aquatic pathogen Streptococcus iniae.
AB  - The aquatic zoonotic pathogen Streptococcus iniae represents a threat to the
      worldwide aquaculture industry and poses a risk to humans who handle raw fish.
      Because little is known about the mechanisms of S. iniae pathogenesis or
      virulence factors, we established a high-throughput system combining whole-genome
      pyrosequencing and transposon mutagenesis that allowed us to identify virulence
      proteins, including Pdi, the polysaccharide deacetylase of S. iniae, that we
      describe here. Using bioinformatics tools, we identified a highly conserved
      signature motif in Pdi that is also conserved in the peptidoglycan deacetylase
      PgdA protein family. A Deltapdi mutant was attenuated for virulence in the hybrid
      striped bass model and for survival in whole fish blood. Moreover, Pdi was found
      to promote bacterial resistance to lysozyme killing and the ability to adhere to
      and invade epithelial cells. On the other hand, there was no difference in the
      autolytic potential, resistance to oxidative killing or resistance to cationic
      antimicrobial peptides between S. iniae wild-type and Deltapdi. In conclusion, we
      have demonstrated that pdi is involved in S. iniae adherence and invasion,
      lysozyme resistance and survival in fish blood, and have shown that pdi plays a
      role in the pathogenesis of S. iniae. Identification of Pdi and other S. iniae
      virulence proteins is a necessary initial step towards the development of
      appropriate preventive and therapeutic measures against diseases and economic
      losses caused by this pathogen.

PMID- 19762442
TI  - Biochemical and genomic analysis of the denitrification pathway within the genus
      Neisseria.
AB  - Since Neisseria gonorrhoeae and Neisseria meningitidis are obligate human
      pathogens, a comparison with commensal species of the same genus could reveal
      differences important in pathogenesis. The recent completion of commensal
      Neisseria genome draft assemblies allowed us to perform a comparison of the genes
      involved in the catalysis, assembly and regulation of the denitrification
      pathway, which has been implicated in the virulence of several bacteria. All
      species contained a highly conserved nitric oxide reductase (NorB) and a nitrite
      reductase (AniA or NirK) that was highly conserved in the catalytic but divergent
      in the N-terminal lipid modification and C-terminal glycosylation domains. Only
      Neisseria mucosa contained a nitrate reductase (Nar), and only Neisseria
      lactamica, Neisseria cinerea, Neisseria subflava, Neisseria flavescens and
      Neisseria sicca contained a nitrous oxide reductase (Nos) complex. The regulators
      of the denitrification genes, FNR, NarQP and NsrR, were highly conserved, except
      for the GAF domain of NarQ. Biochemical examination of laboratory strains
      revealed that all of the neisserial species tested except N. mucosa had a two- to
      fourfold lower nitrite reductase activity than N. gonorrhoeae, while N.
      meningitidis and most of the commensal Neisseria species had a two- to fourfold
      higher nitric oxide (NO) reductase activity. For N. meningitidis and most of the
      commensal Neisseria, there was a greater than fourfold reduction in the NO steady
      state level in the presence of nitrite as compared with N. gonorrhoeae. All of
      the species tested generated an NO steady-state level in the presence of an NO
      donor that was similar to that of N. gonorrhoeae. The greatest difference between
      the Neisseria species was the lack of a functional Nos system in the pathogenic
      species N. gonorrhoeae and N. meningitidis.

PMID- 19762443
TI  - Functional analyses of PAU genes in Saccharomyces cerevisiae.
AB  - PAU genes constitute the largest gene family in Saccharomyces cerevisiae, with 24
      members mostly located in the subtelomeric regions of chromosomes. Little
      information is available about PAU genes, other than expression data for some
      members. In this study, we systematically compared the sequences of all 24
      members, examined the expression of PAU3, PAU5, DAN2, PAU17 and PAU20 in response
      to stresses, and investigated the stability of all Pau proteins. The chromosomal
      localization, synteny and sequence analyses revealed that PAU genes could have
      been amplified by segmental and retroposition duplication through mechanisms of
      chromosomal end translocation and Ty-associated recombination. The coding
      sequences diverged through nucleotide substitution and insertion/deletion of one
      to four codons, thus causing changes in amino acids, truncation or extension of
      Pau proteins. Pairwise comparison of non-coding regions revealed little homology
      in flanking sequences of some members. All 24 PAU promoters contain a TATA box,
      and 22 PAU promoters contain at least one copy of the anaerobic response element
      and the aerobic repression motif. Differential expression was observed among
      PAU3, PAU5, PAU17, PAU20 and DAN2 in response to stress, with PAU5 having the
      highest capacity to be induced by anaerobic conditions, low temperature and wine
      fermentations. Furthermore, Pau proteins with 124 aa were less stable than those
      with 120 or 122 aa. Our results indicate that duplicated PAU genes have been
      evolving, and the individual Pau proteins might possess specific roles for the
      adaptation of S. cerevisiae to certain environmental stresses.

PMID- 19762444
TI  - Cell surface expression of adhesins for fibronectin correlates with virulence in
      Sporothrix schenckii.
AB  - The virulence of four Sporothrix schenckii isolates was compared in a murine
      model of sporotrichosis, together with the protein pattern of the yeast cell
      surface and the capacity to bind the extracellular matrix protein fibronectin.
      Virulence was determined by the mortality rate, fungal burden and histopathology.
      Two clinical isolates were more virulent for C57BL/6 mice, but no direct
      correlation was seen between virulence and the clinical or environmental origin
      of the isolates. The lowest virulence was observed for an isolate recovered from
      a patient with meningeal sporotrichosis. Although all isolates could effectively
      disseminate, the dissemination patterns were not similar. Using flow cytometry
      analysis, we investigated the interaction of all the strains with fibronectin,
      and showed that the binding capacity correlated with virulence. Western blot
      analysis of S. schenckii cell wall extracts revealed positive bands for
      fibronectin in the range of 37-92 kDa. The 70 kDa adhesin was also recognized by
      a protective monoclonal antibody raised against a gp70 antigen of S. schenckii
      (mAb P6E7). Confocal microscopy confirmed the co-localization of fibronectin and
      mAb P6E7 on the yeast cell surface. To our knowledge, this is the first report
      identifying adhesins for fibronectin on the surface of this human pathogen.

PMID- 19762445
TI  - Transcriptional regulation of the novobiocin biosynthetic gene cluster.
AB  - The aminocoumarin antibiotic novobiocin is a gyrase inhibitor formed by a
      Streptomyces strain. The biosynthetic gene cluster of novobiocin spans 23.4 kb
      and contains 20 coding sequences, among them the two regulatory genes novE and
      novG. We investigated the location of transcriptional promoters within this
      cluster by insertion of transcriptional terminator cassettes and RT-PCR analysis
      of the resulting mutants. The cluster was found to contain eight DNA regions with
      promoter activity. The regulatory protein NovG binds to a previously identified
      binding site within the promoter region located upstream of novH, but apparently
      not to any of the other seven promoters. Quantitative real-time PCR was used to
      compare the number of transcripts in a strain carrying an intact novobiocin
      cluster with strains carrying mutated clusters. Both in-frame deletion of the
      regulatory gene novG and insertion of a terminator cassette into the biosynthetic
      gene novH led to a strong reduction of the number of transcripts of the genes
      located between novH and novW. This suggested that these 16 biosynthetic genes
      form a single operon. Three internal promoters are located within this operon but
      appear to be of minor importance, if any, under our experimental conditions.
      Transcription of novG was found to depend on the presence of NovE, suggesting
      that the two regulatory genes, novE and novG, act in a cascade-like mechanism.
      The resistance gene gyrB(R), encoding an aminocoumarin-resistant gyrase B
      subunit, may initially be co-transcribed with the genes from novH to novW.
      However, when the gyrase inhibitor novobiocin accumulates in the cultures,
      gyrB(R) is transcribed from its own promoter. Previous work has suggested that
      this promoter is controlled by the superhelical density of chromosomal DNA.

PMID- 19762446
TI  - The pneumococcal response to oxidative stress includes a role for Rgg.
AB  - Streptococcus pneumoniae resides in the oxygen-rich environment of the upper
      respiratory tract, and therefore the ability to survive in the presence of oxygen
      is an important aspect of its in vivo survival. To investigate how S. pneumoniae
      adapts to oxygen, we determined the global gene expression profile of the micro
      organism in aerobiosis and anaerobiosis. It was found that exposure to aerobiosis
      elevated the expression of 54 genes, while the expression of 15 genes was
      downregulated. Notably there were significant changes in putative genome
      plasticity and hypothetical genes. In addition, increased expression of rgg, a
      putative transcriptional regulator, was detected. To test the role of Rgg in the
      pneumococcal oxidative stress response, an isogenic mutant was constructed. It
      was found that the mutant was sensitive to oxygen and paraquat, but not to
      H(2)O(2). In addition, the absence of Rgg strongly reduced the biofilm-forming
      ability of an unencapsulated pneumococcus. Virulence studies showed that the
      median survival time of mice infected intranasally with the rgg mutant was
      significantly longer than that of the wild-type-infected group, and the animals
      infected with the mutant developed septicaemia later than those infected
      intranasally with the wild-type.

PMID- 19762447
TI  - The Azospirillum brasilense Sp7 noeJ and noeL genes are involved in extracellular
      polysaccharide biosynthesis.
AB  - Azospirillum brasilense is a plant root-colonizing bacterium that exerts
      beneficial effects on the growth of many agricultural crops. Extracellular
      polysaccharides of the bacterium play an important role in its interactions with
      plant roots. The pRhico plasmid of A. brasilense Sp7, also named p90, carries
      several genes involved in synthesis and export of cell surface polysaccharides.
      We generated two Sp7 mutants impaired in two pRhico-located genes, noeJ and noeL,
      encoding mannose-6-phosphate isomerase and GDP-mannose 4,6-dehydratase,
      respectively. Our results demonstrate that in A. brasilense Sp7, noeJ and noeL
      are involved in lipopolysaccharide and exopolysaccharide synthesis. noeJ and noeL
      mutant strains were significantly altered in their outer membrane and
      cytoplasmic/periplasmic protein profiles relative to the wild-type strain.
      Moreover, both noeJ and noeL mutations significantly affected the bacterial
      responses to several stresses and antimicrobial compounds. Disruption of noeL,
      but not noeJ, affected the ability of the A. brasilense Sp7 to form biofilms. The
      pleiotropic alterations observed in the mutants could be due, at least partially,
      to their altered lipopolysaccharides and exopolysaccharides relative to the wild
      type.

PMID- 19762448
TI  - RelA regulates virulence and intracellular survival of Francisella novicida.
AB  - Analysis of the genome of Francisella tularensis has revealed few regulatory
      systems, and how the organism adapts to conditions in different niches is poorly
      understood. The stringent response is a global stress response mediated by
      (p)ppGpp. The enzyme RelA has been shown to be involved in generation of this
      signal molecule in a range of bacterial species. We investigated the effect of
      inactivation of the relA gene in Francisella by generating a mutant in
      Francisella novicida. Under amino acid starvation conditions, the relA mutant was
      defective for (p)ppGpp production. Characterization showed the mutant to grow
      similarly to the wild-type, except that it entered stationary phase later than
      wild-type cultures, resulting in higher cell yields. The relA mutant showed
      increased biofilm formation, which may be linked to the delay in entering
      stationary phase, which in turn would result in higher cell numbers present in
      the biofilm and reduced resistance to in vitro stress. The mutant was attenuated
      in the J774A macrophage cell line and was shown to be attenuated in the mouse
      model of tularaemia, but was able to induce a protective immune response.
      Therefore, (p)ppGpp appears to be an important intracellular signal, integral to
      the pathogenesis of F. novicida.

PMID- 19762450
TI  - Limitations of automated remnant lipoprotein cholesterol assay for diagnostic
      use.

PMID- 19762451
TI  - Associations between psychological distress, learning, and memory in spouse
      caregivers of older adults.
AB  - Family caregivers of older adults experience high levels of chronic stress and
      psychological distress, which are known to impair cognition. Very little
      research, however, has assessed the impact of caregiving on key cognitive
      outcomes such as learning and memory. This study compared 16 spouse caregivers
      with 16 matched controls using standardized neuropsychological measures of
      learning, episodic memory, and working memory. Analyses compared groups on these
      cognitive outcomes and examined whether psychological distress mediated group
      differences in cognition. Results indicated that caregivers were significantly
      more distressed than non-caregivers and exhibited deficits in learning, recall of
      episodic information after short and long delays, and working memory.
      Furthermore, the majority of group differences in cognitive outcomes were
      mediated by psychological distress. This study adds to a small body of literature
      demonstrating impaired cognitive functioning among family caregivers. It also
      suggests that distress is one of a number of possible underlying mechanisms
      leading to disruptions in learning and memory in this population.

PMID- 19762452
TI  - Distinct anatomical subtypes of the behavioural variant of frontotemporal
      dementia: a cluster analysis study.
AB  - The behavioural variant of frontotemporal dementia is a progressive
      neurodegenerative syndrome characterized by changes in personality and behaviour.
      It is typically associated with frontal lobe atrophy, although patterns of
      atrophy are heterogeneous. The objective of this study was to examine case-by
      case variability in patterns of grey matter atrophy in subjects with the
      behavioural variant of frontotemporal dementia and to investigate whether
      behavioural variant of frontotemporal dementia can be divided into distinct
      anatomical subtypes. Sixty-six subjects that fulfilled clinical criteria for a
      diagnosis of the behavioural variant of frontotemporal dementia with a volumetric
      magnetic resonance imaging scan were identified. Grey matter volumes were
      obtained for 26 regions of interest, covering frontal, temporal and parietal
      lobes, striatum, insula and supplemental motor area, using the automated
      anatomical labelling atlas. Regional volumes were divided by total grey matter
      volume. A hierarchical agglomerative cluster analysis using Ward's clustering
      linkage method was performed to cluster the behavioural variant of frontotemporal
      dementia subjects into different anatomical clusters. Voxel-based morphometry was
      used to assess patterns of grey matter loss in each identified cluster of
      subjects compared to an age and gender-matched control group at P < 0.05 (family
      wise error corrected). We identified four potentially useful clusters with
      distinct patterns of grey matter loss, which we posit represent anatomical
      subtypes of the behavioural variant of frontotemporal dementia. Two of these
      subtypes were associated with temporal lobe volume loss, with one subtype showing
      loss restricted to temporal lobe regions (temporal-dominant subtype) and the
      other showing grey matter loss in the temporal lobes as well as frontal and
      parietal lobes (temporofrontoparietal subtype). Another two subtypes were
      characterized by a large amount of frontal lobe volume loss, with one subtype
      showing grey matter loss in the frontal lobes as well as loss of the temporal
      lobes (frontotemporal subtype) and the other subtype showing loss relatively
      restricted to the frontal lobes (frontal-dominant subtype). These four subtypes
      differed on clinical measures of executive function, episodic memory and
      confrontation naming. There were also associations between the four subtypes and
      genetic or pathological diagnoses which were obtained in 48% of the cohort. The
      clusters did not differ in behavioural severity as measured by the
      Neuropsychiatric Inventory; supporting the original classification of the
      behavioural variant of frontotemporal dementia in these subjects. Our findings
      suggest behavioural variant of frontotemporal dementia can therefore be
      subdivided into four different anatomical subtypes.

PMID- 19762453
TI  - Morbus Crohn--a disease of failing macroautophagy in the immune system?
AB  - Mutations in genes involved in macroautophagy have been found to be associated
      with Morbus Crohn, also called Crohn's disease (CD), an inflammatory bowel
      disease. Taking this disease as an example for pathogenesis due to altered
      macroautophagy, we discuss here how macroautophagy supports innate and adaptive
      immunity. This support ranges from maintenance of components of the immune
      system, antigen processing for presentation to the immune system, to education of
      the immune system in order to distinguish self from dangerous non-self. A better
      understanding of these mechanisms should allow us not only to develop
      therapeutical strategies for CD but also to utilize macroautophagy for enhanced
      immunity against pathogens and tumors.

PMID- 19762454
TI  - Histidine decarboxylase but not histamine receptor 1 or 2 deficiency protects
      from K/BxN serum-induced arthritis.
AB  - Serum transfer from arthritic K/BxN mice into naive animals results in arthritis.
      Mast cells have been shown to be essential since mice lacking these cell type do
      not develop arthritis upon serum injection. Mast cell function depends on the
      release of granules filled with mediators such as histamine. Mice deficient in
      histidine decarboxylase (HDC(-/-)) that do not produce histamine and mice
      deficient for histamine receptor 1 (H1R(-/-)) or histamine receptor 2 (H2R(-/-))
      were injected with arthritogenic sera from the K/BxN mice, and the progression of
      arthritis was observed through the next 2 weeks. HDC(-/-) mice that are histamine
      free developed a milder form of arthritis in comparison with the wild-type
      controls. In both receptor-deficient mice as well as in wild-type controls, the
      onset and severity of clinical arthritis and ankle thickening occurred during day
      1 to 3. These results indicate that histamine is required but not indispensable
      for the development of serum-induced arthritis and histamine receptors other than
      those studied here may be involved.

PMID- 19762456
TI  - Costs of Mediterranean and western dietary patterns in a Spanish cohort and their
      relationship with prospective weight change.
AB  - BACKGROUND: There is a scarcity of studies evaluating the relationship between
      food costs and adherence to different food patterns and obesity. METHODS: This
      was a dynamic cohort of Spanish university graduates (n = 17,197 for the cross
      sectional baseline assessment and n = 11,195 for the prospective follow-up
      analyses). Mean age was 38.6 (SD 12.2) years, and 60% of participants were women.
      A 136-item food frequency questionnaire previously validated in Spain was used.
      Principal component analysis (PCA) was used to derive dietary patterns. Average
      cost of food was calculated from official Spanish government data. Self-reported
      weight was previously validated in the cohort. Body weight was assessed both at
      baseline and during follow-up. RESULTS: PCA identified two dietary patterns,
      designated as western and Mediterranean. Participants with the highest scores on
      the western dietary pattern (fifth quintile vs first quintile) spent less money (
      0.64 euro (-$0.80) per 1000 kcal (95% CI -0.68 euro to -0.61 euro, p for trend
      <0.001)) on their daily food costs, whereas the opposite was true for the
      Mediterranean dietary pattern (+0.71 euro (+$0.90) (95% CI +0.67 euro to +0.74
      euro, p for trend <0.001). After adjusting for dietary pattern scores and other
      potential confounders, higher daily food costs were significantly associated with
      greater weight gain. CONCLUSIONS: These data suggest that a Mediterranean dietary
      pattern is more expensive to follow than a western dietary pattern. This economic
      barrier should be considered when counselling patients about following a healthy
      diet because cost may be a prohibitive factor.

PMID- 19762455
TI  - Ethnic differences in human papillomavirus awareness and vaccine acceptability.
AB  - BACKGROUND: Studies of human papillomavirus (HPV) awareness and HPV vaccine
      acceptability have included few non-white participants, making it difficult to
      explore ethnic differences. This study assessed HPV awareness and HPV vaccine
      acceptability in a sample of women representing the major UK ethnic minority
      groups. METHODS: A cross-sectional study design was used to assess awareness of
      HPV and acceptability of HPV vaccination. Participants were recruited using quota
      sampling to ensure adequate representation of ethnic minority women: Indian,
      Pakistani, Bangladeshi, Caribbean, African and Chinese women (n = 750). A
      comparison sample of white British women (n = 200) was also recruited. RESULTS:
      Awareness of HPV was lower among ethnic minority women than among white women (6
      18% vs 39% in white women), and this was not explained by generational status or
      language spoken at home. In a subsample who were mothers (n = 601), ethnicity and
      religion were strongly associated with acceptability of HPV vaccination.
      Acceptability was highest among white mothers (63%) and lowest among South Asians
      (11-25%). Those from non-Christian religions were also less accepting of the
      vaccine (17-34%). The most common barriers to giving HPV vaccination were a need
      for more information, sex-related concerns and concern about side-effects. South
      Asian women were the most likely to cite sex-related concerns, and were also
      least likely to believe the vaccine would offer their daughters protection.
      CONCLUSION: These findings suggest some cultural barriers that could be addressed
      in tailored information aimed at ethnic minority groups. They also highlight the
      importance of recording ethnicity as part of HPV vaccine uptake data.

PMID- 19762457
TI  - A new reference line for the brain CT: the tuberculum sellae-occipital
      protuberance line is parallel to the anterior/posterior commissure line.
AB  - BACKGROUND AND PURPOSE: CT and MR imaging of the brain have diverged reference
      lines. Modified Talairach anterior/posterior commissure (ACPC) line is widely
      accepted as the standard for clinical brain MR imaging, while orbitomeatal line
      (OML) is used for CT. This study sought to determine an appropriate reference
      line for brain CT parallel to the ACPC line. MATERIALS AND METHODS: We measured
      the angles between the ACPC line and the OML, the line connecting the tuberculum
      sellae and the internal occipital protuberance (TS-IOP line), and the line
      connecting the tuberculum sellae and the external occipital protuberance (TS-EOP
      line) on midsagittal brain MR images of 223 patients. In addition, with the hard
      palate as the basis, the angles to the ACPC line in the brain MR images and new
      reference line on the brain CT images from the same patient were measured, and
      the difference between the 2 angles was calculated in 30 patients. In the same
      method, the angles to the OML in the brain CT images and the ACPC line on the
      brain MR images were measured, and their difference was calculated in 30
      patients. Then the 2 difference values were compared with verification of the new
      reference line. RESULTS: The angles between the ACPC line and both the TS-IOP
      line (0.0 degrees +/- 4.0 degrees ) and the TS-EOP line (0.8 degrees +/- 3.2
      degrees ) were significantly smaller than the angles between the ACPC line and
      the OML (-12.6 degrees +/- 4.2 degrees ; P < .05). In actual scanned images, the
      angle differences between the TS-OP (TS-IOP + TS-EOP) line and the ACPC line (0.3
      degrees +/- 4.5 degrees ) were statistically smaller than the angles between the
      OML and the ACPC line (-6.6 degrees +/- 3.9 degrees ; P < .05). CONCLUSIONS: TS
      OP lines are nearly parallel to the ACPC line.

PMID- 19762458
TI  - A prospective study of fetuses with isolated ventriculomegaly investigated by
      antenatal sonography and in utero MR imaging.
AB  - BACKGROUND AND PURPOSE: Fetal ventriculomegaly (VM) is important because of its
      high prevalence and high risk of association with other brain abnormalities. The
      purpose of this article was to investigate the hypotheses that including in utero
      MR imaging (iuMR) in the diagnostic pathway for fetuses with isolated VM on
      antenatal imaging will show other brain abnormalities in a high proportion of
      cases and that these will have a significant effect on clinical management.
      MATERIALS AND METHODS: One hundred forty-seven pregnant women were recruited
      prospectively from 8 fetomaternal centers in Britain. All of the fetuses had VM
      diagnosed on sonography but no other abnormality. iuMR was performed, and the
      results of the examinations were compared with those of sonography. Two
      fetomaternal experts made independent assessments of the effects of any new
      diagnoses on clinical management. RESULTS: Categoric assessments of ventricular
      size were the same in approximately 90% of fetuses. Other abnormalities were
      shown in 17% of fetuses. The most frequent additional brain abnormality shown on
      iuMR was agenesis of the corpus callosum. Severe VM was associated with an
      approximately 10-fold increase in the risk of another brain abnormality being
      present when compared with fetuses with mild VM. The most profound effects on
      clinical management, however, were found in cases of mild VM. CONCLUSIONS: This
      work supports our hypotheses by showing a high detection rate of other brain
      pathology when iuMR was used to supplement antenatal sonography (17%). In a high
      proportion of cases, the detection of the extra pathology would have led to
      significant changes in clinical management.

PMID- 19762459
TI  - Intra- and extracranial solitary fibrous tumor of the trigeminal nerve: CT and MR
      imaging appearance.
AB  - We describe a rare case of SFT existing along the mandibular division of the
      trigeminal nerve and extending down into the infratemporal fossa through the
      foramen ovale. The tumor showed heterogeneous hypointensity on T2-weighted images
      and marked enhancement on CT and MR images.

PMID- 19762460
TI  - Intracranial blood-flow velocity and pressure measurements using an intra
      arterial dual-sensor guidewire.
AB  - Hemodynamics is thought to play a role in the growth and rupture of intracranial
      aneurysms. In 4 patients, we obtained local pressure and BFV by using a dual
      sensor pressure and Doppler velocity wire within and in vessels surrounding
      unruptured aneurysms. Local BFVs can serve as boundary conditions for
      computational fluid dynamics, whereas pressure recordings provide direct
      information on the mechanical load imposed on the aneurysm. Both measurements may
      thus add to patient-specific rupture-risk assessment.

PMID- 19762461
TI  - Dualism: from Descartes and Bacon to AJNR.

PMID- 19762462
TI  - Intrathecal gadolinium-enhanced MR cisternography in the evaluation of CSF
      leakage.
AB  - BACKGROUND AND PURPOSE: Radiologic identification of the location of the CSF
      leakage is important for proper surgical planning and increases the chance of
      dural repair. This article describes our experience in analyzing clinically
      suspected cranial CSF fistulas by using MR imaging combined with the intrathecal
      administration of a gadolinium-based contrast agent. MATERIALS AND METHODS: A
      total of 85 consecutive patients with suspected CSF fistulas who presented with
      persistent or intermittent rhinorrhea or otorrhea lasting for more than 1 month
      between 2003 and 2007 were included in this study. RESULTS: We observed objective
      CSF leakage in 64 of 85 patients (75%). The CSF leak was located in the ethmoidal
      region in 37 patients (58%), in the superior wall of the sphenoid sinus in 8
      patients (13%), in the posterior wall of the frontal sinus in 10 patients (15%),
      in the superior wall of the mastoid air cells in 6 patients (9%), and from the
      skull base into the infratemporal fossa in 1 patient (2%). Two patients (3%)
      showed leakage into >1 paranasal sinus. CONCLUSIONS: MR cisternography after the
      intrathecal administration of gadopentate dimeglumine represents an effective and
      minimally invasive method for evaluating suspected CSF fistulas along the skull
      base. It provides multiplanar capabilities without risk of radiation exposure and
      is an excellent approach to depict the anatomy of CSF spaces and CSF fistulas.

PMID- 19762463
TI  - Imaging and treatment of sacral insufficiency fractures.
AB  - SIFs are a common, though often unsuspected, cause of low back pain in the
      elderly. Although numerous radiographic modalities can be used to diagnose SIFs,
      bone scintigraphy and MR imaging are the most sensitive. Conservative management
      involves various combinations of bed rest, rehabilitation, and analgesics. More
      recently, sacroplasty has emerged as an alternative therapy for the treatment of
      SIFs, with prospective studies and case reports suggesting that it is a safe and
      effective therapy. This article reviews the imaging appearance of SIFs and
      discusses treatment options with a focus on sacroplasty.

PMID- 19762464
TI  - A compartment-based approach for the imaging evaluation of tinnitus.
AB  - Tinnitus affects 10% of the US general population and is a common indication for
      imaging studies. We describe a sequential compartment-based diagnostic approach,
      which simplifies the interpretation of imaging studies in patients with tinnitus.
      The choice of the initial imaging technique depends on the type of tinnitus,
      associated symptoms, and examination findings. Familiarity with the
      pathophysiologic mechanisms of tinnitus and the imaging findings is a
      prerequisite for a tailored diagnostic approach by the radiologist.

PMID- 19762465
TI  - The Ig domain protein CD9P-1 down-regulates CD81 ability to support Plasmodium
      yoelii infection.
AB  - Invasion of hepatocytes by Plasmodium sporozoites is a prerequisite for
      establishment of a malaria natural infection. The molecular mechanisms underlying
      sporozoite invasion are largely unknown. We have previously reported that CD81 is
      required on hepatocytes for infection by Plasmodium falciparum and Plasmodium
      yoelii sporozoites. CD81 belongs to the tetraspanin superfamily of transmembrane
      proteins. By interacting with each other and with other transmembrane proteins,
      tetraspanins may play a role in the lateral organization of membrane proteins. In
      this study, we investigated the role of the two major molecular partners of CD81
      in hepatocytic cells, CD9P-1/EWI-F and EWI-2, two transmembrane proteins
      belonging to a novel subfamily of immunoglobulin proteins. We show that CD9P-1
      silencing increases the host cell susceptibility to P. yoelii sporozoite
      infection, whereas EWI-2 knock-down has no effect. Conversely, overexpression of
      CD9P-1 but not EWI-2 partially inhibits infection. Using CD81 and CD9P-1 chimeric
      molecules, we demonstrate the role of transmembrane regions in CD81-CD9P-1
      interactions. Importantly, a CD9P-1 chimera that no longer associates with CD81
      does not affect infection. Based on these data, we conclude that CD9P-1 acts as a
      negative regulator of P. yoelii infection by interacting with CD81 and regulating
      its function.

PMID- 19762466
TI  - A distributed set of interactions controls mu2 functionality in the role of AP-2
      as a sorting adaptor in synaptic vesicle endocytosis.
AB  - The mechanisms of how, following exocytosis, the approximately nine types of
      synaptic vesicle (SV) transmembrane proteins are accurately resorted to form SVs
      are poorly understood. The time course of SV endocytosis is very sensitive to
      perturbations in clathrin and dynamin, supporting the model that SV endocytosis
      occurs through a clathrin-mediated pathway. We recently demonstrated that removal
      of the clathrin adaptor protein AP-2, the key protein thought to coordinate cargo
      selection into clathrin-coated pits, results in a significant impairment in
      endocytosis kinetics. Endocytosis, however, still proceeds in the absence of AP
      2, bringing into question the role of AP-2 in cargo sorting in this process.
      Using quantitative endocytosis assays at nerve terminals, we examined how
      endocytosis depends on the integrity of mu2 function. Our experiments indicate
      that no single perturbation in mu2 prevents restoration of endocytic function
      when mutated mu2 replaces native mu2, whereas introduction of multiple
      distributed mutations significantly impairs endocytosis. We also examined whether
      the presence of AP-2 is important for the functionality of the previously
      identified endocytic motif in an SV cargo protein, the dileucine motif in vGlut
      1. These data show that while mutations in the dileucine motif slow the retrieval
      of vGlut-1, they only do so in the presence of AP-2. These data thus indicate
      that AP-2 plays a role in cargo selection but that no single aspect of mu2
      function is critical, implying that a more distributed network of interactions
      supports AP-2 function in SV endocytosis.

PMID- 19762467
TI  - The mercaptopyruvate sulfurtransferase of Trichomonas vaginalis links cysteine
      catabolism to the production of thioredoxin persulfide.
AB  - Trichomonas vaginalis is a protozoan parasite of humans that is able to
      synthesize cysteine de novo using cysteine synthase but does not produce
      glutathione. In this study, high pressure liquid chromatography analysis
      confirmed that cysteine is the major intracellular redox buffer by showing that
      T. vaginalis contains high levels of cysteine ( approximately 600 mum) comprising
      more than 70% of the total thiols detected. To investigate possible mechanisms
      for the regulation of cysteine levels in T. vaginalis, we have characterized
      enzymes of the mercaptopyruvate pathway. This consists of an aspartate
      aminotransferase (TvAspAT1), which transaminates cysteine to form 3
      mercaptopyruvate (3-MP), and mercaptopyruvate sulfurtransferase (TvMST), which
      transfers the sulfur of 3-MP to a nucleophilic acceptor, generating pyruvate.
      TvMST has high activity with 3-MP as a sulfur donor and can use several thiol
      compounds as sulfur acceptor substrates. Our analysis indicated that TvMST has a
      k(cat)/K(m) for reduced thioredoxin of 6.2 x 10(7) m(-1) s(-1), more than 100
      fold higher than that observed for beta-mercaptoethanol and cysteine, suggesting
      that thioredoxin is a preferred substrate for TvMST. Thiol trapping and mass
      spectrometry provided direct evidence for the formation of thioredoxin persulfide
      as a product of this reaction. The thioredoxin persulfide could serve a
      biological function such as the transfer of the persulfide to a target protein or
      the sequestered release of sulfide for biosynthesis. Changes in MST activity of
      T. vaginalis in response to variation in the supply of exogenous cysteine are
      suggestive of a role for the mercaptopyruvate pathway in the removal of excess
      intracellular cysteine, redox homeostasis, and antioxidant defense.

PMID- 19762468
TI  - Identification of critical residues within the conserved and specificity patches
      of nerve growth factor leading to survival or differentiation.
AB  - Afflicted neurons in Alzheimer disease have been shown to display an imbalance in
      the expression of TrkA and p75(NTR) at the cell surface, and administration of
      nerve growth factor (NGF) has been considered and attempted for treatment.
      However, wild-type NGF causes extensive elaboration of neurites while providing
      survival support. This study was aimed at developing recombinant NGF muteins that
      did not support neuritogenesis while maintaining the survival response. Critical
      residues were identified at the ligand-receptor interface by point mutagenesis
      that played a greater importance in neuritogenesis versus survival. By combining
      point mutations, two survival-selective recombinant NGF muteins, i.e./7-84-103
      and KKE/7-84-103, were generated. Both muteins reduced neuritogenesis in PC12
      (TrkA(+)/p75(NTR+)) cells by >90%, while concurrently retaining near wild-type
      survival activity in MG139 (TrkA(+) only) and PCNA fibroblast (p75(NTR+)-only)
      cells. Additionally, survival in both naive and terminally differentiated PC12
      cells was shown to be intermediate between NGF and negative controls. Dose
      response curves with 7-84-103 showed that the differentiation curve was shifted
      by about 100-fold, whereas the EC(50) for survival was only increased by 3.3
      fold. Surface plasmon resonance analysis revealed a 200-fold decrease in binding
      of 7-84-103 to TrkA. The retention of cell survival was attributed to maintenance
      of signaling through the Akt survival pathway with reduced MAPK signaling for
      differentiation. The effect of key mutations along the NGF receptor interface are
      transmitted inside the cell to enable the generation of survival-selective
      recombinant NGF muteins that may represent novel pharmacologic lead agents for
      the amelioration of Alzheimer disease.

PMID- 19762469
TI  - Polypyrimidine tract binding protein prevents activity of an intronic regulatory
      element that promotes usage of a composite 3'-terminal exon.
AB  - Alternative splicing of 3'-terminal exons plays a critical role in gene
      expression by producing mRNA with distinct 3'-untranslated regions that regulate
      their fate and their expression. The Xenopus alpha-tropomyosin pre-mRNA possesses
      a composite internal/3'-terminal exon (exon 9A9') that is differentially
      processed depending on the embryonic tissue. Exon 9A9' is repressed in non-muscle
      tissue by the polypyrimidine tract binding protein, whereas it is selected as a
      3'-terminal or internal exon in myotomal cells and adult striated muscles,
      respectively. We report here the identification of an intronic regulatory
      element, designated the upstream terminal exon enhancer (UTE), that is required
      for the specific usage of exon 9A9' as a 3'-terminal exon in the myotome. We
      demonstrate that polypyrimidine tract binding protein prevents the activity of
      UTE in non-muscle cells, whereas a subclass of serine/arginine rich (SR) proteins
      promotes the selection of exon 9A9' in a UTE-dependent way. Morpholino-targeted
      blocking of UTE in the embryo strongly reduced the inclusion of exon 9A9' as a 3'
      terminal exon in the endogenous mRNA, demonstrating the function of UTE under
      physiological circumstances. This strategy allowed us to reveal a splicing
      pathway that generates a mRNA with no in frame stop codon and whose steady-state
      level is translation-dependent. This result suggests that a non-stop decay
      mechanism participates in the strict control of the 3'-end processing of the
      alpha-tropomyosin pre-mRNA.

PMID- 19762470
TI  - Identification of a Sam68 ribonucleoprotein complex regulated by epidermal growth
      factor.
AB  - Sam68, Src associated in mitosis of 68 kDa, is a known RNA-binding protein and a
      signaling adaptor protein for tyrosine kinases. However, the proteins associated
      with Sam68 and the existence of a Sam68 complex, its mass, and regulation are,
      however, unknown. Herein we identify a large Sam68 complex with a mass >1 MDa in
      HeLa cells that is composed of approximately 40 proteins using an
      immunoprecipitation followed by a mass spectrometry approach. Many of the
      proteins identified are RNA-binding proteins and are known components of a
      previously identified structure termed the spreading initiation center. The large
      Sam68 complex is a ribonucleoprotein complex, as treatment with RNases caused a
      shift in the molecular mass of the complex to 200-450 kDa. Moreover, treatment of
      HeLa cells with phorbol 12-myristate 13-acetate or epidermal growth factor
      induced the disassociation of Sam68 from the large complex and the appearance of
      Sam68 within the smaller complex. Actually, in certain cell lines such as breast
      cancer cell lines MCF-7 and BT-20, Sam68 exists in equilibrium between a large
      and a small complex. The appearance of the small Sam68 complex in cells
      correlates with the ability of Sam68 to promote the alternative splicing of CD44
      and cell migration. Our findings show that Sam68 exists in equilibrium in
      transformed cells between two complexes and that extracellular signals, such as
      epidermal growth factor stimulation, promote alternative splicing by modulating
      the composition of the Sam68 complex.

PMID- 19762471
TI  - Biochemical characterization of two wheat phosphoethanolamine N-methyltransferase
      isoforms with different sensitivities to inhibition by phosphatidic acid.
AB  - In plants the triple methylation of phosphoethanolamine to phosphocholine
      catalyzed by phosphoethanolamine N-methyltransferase (PEAMT) is considered a rate
      limiting step in the de novo synthesis of phosphatidylcholine. Besides being a
      major membrane phospholipid, phosphatidylcholine can be hydrolyzed into choline
      and phosphatidic acid. Phosphatidic acid is widely recognized as a second
      messenger in stress signaling, and choline can be oxidized within the chloroplast
      to yield the putative osmoprotectant glycine betaine. Here we describe the
      cloning and biochemical characterization of a second wheat PEAMT isoform that has
      a four times higher specific activity than the previously described
      WPEAMT/TaPEAMT1 enzyme and is less sensitive to product inhibition by S-adenosyl
      homocysteine, but more sensitive to inhibition by phosphocholine. Both enzymes
      follow a sequential random Bi Bi mechanism and show mixed-type product inhibition
      patterns with partial inhibition for TaPEAMT1 and a strong non-competitive
      component for TaPEAMT2. An induction of TaPEAMT protein expression and activity
      is observed after cold exposure, ahead of an increase in gene expression. Our
      results demonstrate direct repression of in vitro enzymatic activities by
      phosphatidic acid for both enzymes, with TaPEAMT1 being more sensitive than
      TaPEAMT2 in the physiological concentration range. Other lipid ligands identified
      in protein-lipid overlays are phosphoinositide mono- as well as some di
      phosphates and cardiolipin. These results provide new insights into the complex
      regulatory circuits of phospholipid biosynthesis in plants and underline the
      importance of head group biosynthesis in adaptive stress responses.

PMID- 19762472
TI  - Mitochondrial localization of PARP-1 requires interaction with mitofilin and is
      involved in the maintenance of mitochondrial DNA integrity.
AB  - Poly(ADP-ribose)polymerase-1 (PARP-1) is a predominantly nuclear enzyme that
      exerts numerous functions in cellular physiology and pathology, from maintenance
      of DNA stability to transcriptional regulation. Through a proteomic analysis of
      PARP-1 co-immunoprecipitation complexes, we identified Mitofilin, a mitochondrial
      protein, as a new PARP-1 interactor. This result prompted us to further
      investigate the presence and the role of the enzyme in mitochondria. Using laser
      confocal microscopy and Western blot analysis of purified mitochondria, we
      demonstrated the mitochondrial localization of a fraction of PARP-1. Further, the
      effects of overexpressing or down-regulating Mitofilin showed that this protein
      promotes and is required for PARP-1 mitochondrial localization. We also report
      several lines of evidence suggesting that intramitochondrial PARP-1 plays a role
      in mitochondrial DNA (mtDNA) damage signaling and/or repair. First, we show that
      PARP-1 binds to different regions throughout the mtDNA. Moreover, we demonstrated
      that the depletion of either PARP-1 or Mitofilin, which abrogates the
      mitochondrial localization of the enzyme, leads to the accumulation of mtDNA
      damage. Finally, we show that DNA ligase III, known to be required for mtDNA
      repair, participates in a PARP-1-containing complex bound to mtDNA. This work
      highlights a new environment for PARP-1, opening the possibility that at least
      some of the nuclear functions of the enzyme can be also extended to mtDNA
      metabolism.

PMID- 19762473
TI  - A conserved membrane attachment site in alpha-SNAP facilitates N-ethylmaleimide
      sensitive factor (NSF)-driven SNARE complex disassembly.
AB  - The ATPase NSF (N-ethylmaleimide-sensitive factor) and its SNAP (soluble N
      ethylmaleimide-sensitive factor attachment protein) cofactor constitute the
      ubiquitous enzymatic machinery responsible for recycling of the SNARE (SNAP
      receptor) membrane fusion machinery. The enzyme uses the energy of ATP hydrolysis
      to dissociate the constituents of the SNARE complex, which is formed during the
      fusion of a transport vesicle with the acceptor membrane. However, it is still
      unclear how NSF and the SNAP adaptor work together to take the tight SNARE bundle
      apart. SNAPs have been reported to attach to membranes independently from SNARE
      complex binding. We have investigated how efficient the disassembly of soluble
      and membrane-bound substrates are, comparing the two. We found that SNAPs support
      disassembly of membrane-bound SNARE complexes much more efficiently. Moreover, we
      identified a putative, conserved membrane attachment site in an extended loop
      within the N-terminal domain of alpha-SNAP. Mutation of two highly conserved,
      exposed phenylalanine residues on the extended loop prevent SNAPs from
      facilitating disassembly of membrane-bound SNARE complexes. This implies that the
      disassembly machinery is adapted to attack membrane-bound SNARE complexes,
      probably in their relaxed cis-configuration.

PMID- 19762474
TI  - Hypoxia-inducible factor-1-mediated regulation of semaphorin 4D affects tumor
      growth and vascularity.
AB  - Tumor progression and metastasis depend on the ability of cancer cells to
      initiate angiogenesis to ensure delivery of oxygen, nutrients, and growth factors
      to tumor cells and provide access to the systemic circulation. Hypoxia-inducible
      factor-1 (HIF-1) can activate expression of a broad range of genes that mediate
      many of the adaptive responses to decreased oxygen concentration, such as
      enhanced glucose uptake and formation of new blood vessels. Acting through Plexin
      B1 on endothelial cells, Semaphorin 4D (Sema4D) has been shown to promote
      angiogenesis and enhance invasive growth and proliferation in some tumors. Here
      we show that the gene for Sema4D, the product of which is elevated in head and
      neck squamous cell carcinoma (HNSCC) cells, contains upstream hypoxia response
      elements (HRE) and is strongly induced in hypoxia in a HIF-1-dependent manner.
      Knocking down Sema4D expression with short hairpin (sh) RNA reduces in vitro
      endothelial cell migration and growth and vascularity of HNSCC xenografts
      expressing a degradation resistant HIF-1alpha subunit. We also demonstrate a
      correlation between HIF-1 activity and Sema4D expression in HNSCC specimens.
      These findings indicate that Sema4D is induced by hypoxia in a HIF-1-dependent
      manner and influences endothelial cell migration and tumor vascularity.
      Expression of Sema4D may be a strategy by which carcinomas promote angiogenesis
      and therefore could represent a therapeutic target for these malignancies.

PMID- 19762476
TI  - Subinhibitory concentrations of moxifloxacin decrease adhesion and biofilm
      formation of Stenotrophomonas maltophilia from cystic fibrosis.
AB  - Stenotrophomonas maltophilia is an emerging nosocomial bacterial pathogen that is
      currently isolated with increasing frequency from the airways of cystic fibrosis
      (CF) patients. In this study the effect of subinhibitory concentrations (subMICs)
      of moxifloxacin on adhesion, biofilm formation and cell-surface hydrophobicity of
      two strains of S. maltophilia isolated from CF patients were evaluated. Adhesion
      and biofilm formation assays were carried out on polystyrene and quantified by
      colony counts. Cell-surface hydrophobicity was determined by a test for adhesion
      to n-hexadecane. Moxifloxacin at 0.03x and 0.06x MIC caused a significant
      decrease in adhesion and biofilm formation by both strains tested. A significant
      reduction in cell-surface hydrophobicity following exposure to subMICs of
      moxifloxacin was observed for one strain only. The results of the present study
      provide an additional rationale for the use of moxifloxacin in CF patients and
      more generally in biofilm-related infections involving S. maltophilia.

PMID- 19762475
TI  - Modulation of OPG, RANK and RANKL by human chondrocytes and their implication
      during osteoarthritis.
AB  - OBJECTIVES: Earlier studies suggest the involvement of osteoprotegerin (OPG),
      RANK and RANK ligand (RANKL) in OA subchondral bone metabolism; however, few
      studies have looked at their functional consequences on chondrocytes. We compared
      the expression/production of OPG, RANK and RANKL on human normal and OA
      chondrocytes, and evaluated, on OA chondrocytes, their modulation by some
      catabolic factors. Furthermore, the role of OPG and RANKL on the production of
      catabolic/anabolic factors was assessed. METHODS: Expression was determined using
      real-time PCR, production of RANK and RANKL by flow cytometry and that of OPG by
      ELISA. Modulation of these factors was determined upon treatment with IL-1beta,
      TNF-alpha and PGE(2). The functional consequences were examined following
      treatment with soluble RANKL or OPG-Fc (OPG without the heparin-binding domain).
      RESULTS: OPG, RANK and RANKL were expressed and produced by human chondrocytes.
      Membranous RANK was produced only by an OA chondrocyte subpopulation (29%)
      localized throughout the cartilage. The OPG/RANKL ratio was significantly (P =
      0.05) reduced on the OA chondrocytes, whereas the RANK/RANKL ratio was
      significantly (P < 0.03) increased. OPG and membranous RANKL levels were
      significantly enhanced by IL-1beta, TNF-alpha and PGE(2), whereas membranous RANK
      was significantly increased only with IL-1beta. Administration of soluble RANKL
      had no effect on the OA chondrocytes. However, addition of OPG-Fc significantly
      stimulated MMP-13 (P = 0.05) and protease-activated receptor-2 (PAR-2) (P < 0.04)
      production. CONCLUSIONS: Our findings showed that human chondrocytes express and
      produce OPG, RANK and RANKL. OA chondrocyte treatment with catabolic factors
      pointed towards an increased biological effect of OPG. Interestingly, OPG appears
      to be involved in OA progression by increasing two catabolic factors involved in
      cartilage pathophysiology.

PMID- 19762477
TI  - Effect of bile salts on the DNA and membrane integrity of enteric bacteria.
AB  - Enteric bacteria are able to resist the high concentrations of bile encountered
      throughout the gastrointestinal tract. Here we review the current mechanisms
      identified in the enteric bacteria Salmonella, Escherichia coli, Bacillus cereus
      and Listeria monocytogenes to resist the dangerous effects of bile. We describe
      the role of membrane transport systems, and their connection with DNA repair
      pathways, in conferring bile resistance to these enterics. We discuss the
      findings from recent investigations that indicate bile tolerance is dependent
      upon being able to resist the detergent properties of bile at both the membrane
      and DNA level.

PMID- 19762478
TI  - Increases in body mass index over a 7-year period and risk of cause-specific
      mortality in Korean men.
AB  - BACKGROUND: The association between increased body mass index (BMI) and
      subsequent mortality remains unclear in Asians. This study investigated the
      associations between BMI increases and cause-specific mortality in middle-aged
      Korean men. METHODS: We conducted a retrospective cohort study of 473 358 Korean
      men aged 30-64 years, who had undergone health examinations in both 1992 and 1998
      and were followed up during 1998-2004. Cox proportional hazards for cause
      specific 7-year mortality in relation to BMI changes after stratification of
      baseline BMI status were analysed. RESULTS: Mortality from cardiovascular disease
      (CVD) was associated with BMI in both 1992 and 1998. Non-CVD mortality was
      inversely associated with BMI in both 1992 and 1998. We cross-classified
      participants into groups based on their baseline BMI levels and percent BMI
      changes during follow-up; men with the lowest BMI level at baseline (BMI in 1992
      <21 kg/m(2)) and stable BMI during follow-up (percent change in BMI <5%) were
      included in the reference category. Compared with the reference group, CVD
      mortality was higher in initially obese men (BMI in 1992 > or =25 kg/m(2)) with
      any increase of BMI, and in initially lean men (BMI in 1992 <21 kg/m(2)) or
      initially overweight men (BMI in 1992 23-24.9 kg/m(2)) with BMI increases of > or
      =10%. BMI increases of 5.0-9.9% in men with baseline BMI <25 kg/m(2) and stable
      BMI in men with baseline BMI > or =21 kg/m(2) appeared to lower the risk for non
      CVD or all-cause mortality, to below the levels seen in the reference group.
      CONCLUSIONS: Among middle-aged Korean men, obesity or severe weight gain was
      detrimental to CVD mortality. An increase in BMI appeared to have a predictive
      value for CVD mortality, especially when used in combination with baseline BMI
      level. In contrast, moderate weight gain in non-obese men seemed to protect
      against non-CVD and all-cause mortality.

PMID- 19762479
TI  - DNA translocation activity of the multifunctional replication protein ORF904 from
      the archaeal plasmid pRN1.
AB  - The replication protein ORF904 from the plasmid pRN1 is a multifunctional enzyme
      with ATPase-, primase- and DNA polymerase activity. Sequence analysis suggests
      the presence of at least two conserved domains: an N-terminal prim/pol domain
      with primase and DNA polymerase activities and a C-terminal superfamily 3
      helicase domain with a strong double-stranded DNA dependant ATPase activity. The
      exact molecular function of the helicase domain in the process of plasmid
      replication remains unclear. Potentially this motor protein is involved in duplex
      remodelling and/or origin opening at the plasmid replication origin. In support
      of this we found that the monomeric replication protein ORF904 forms a hexameric
      ring in the presence of DNA. It is able to translocate along single-stranded DNA
      in 3'-5' direction as well as on double-stranded DNA. Critical residues important
      for ATPase activity and DNA translocation activity were identified and are in
      agreement with a homology model of the helicase domain. In addition we propose
      that a winged helix DNA-binding domain at the C-terminus of the helicase domain
      could assist the binding of the replication protein specifically to the
      replication origin.

PMID- 19762480
TI  - FIGfams: yet another set of protein families.
AB  - We present FIGfams, a new collection of over 100,000 protein families that are
      the product of manual curation and close strain comparison. Using the Subsystem
      approach the manual curation is carried out, ensuring a previously unattained
      degree of throughput and consistency. FIGfams are based on over 950,000 manually
      annotated proteins and across many hundred Bacteria and Archaea. Associated with
      each FIGfam is a two-tiered, rapid, accurate decision procedure to determine
      family membership for new proteins. FIGfams are freely available under an open
      source license. These can be downloaded at ftp://ftp.theseed.org/FIGfams/. The
      web site for FIGfams is http://www.theseed.org/wiki/FIGfams/

PMID- 19762481
TI  - MGEScan-non-LTR: computational identification and classification of autonomous
      non-LTR retrotransposons in eukaryotic genomes.
AB  - Computational methods for genome-wide identification of mobile genetic elements
      (MGEs) have become increasingly necessary for both genome annotation and
      evolutionary studies. Non-long terminal repeat (non-LTR) retrotransposons are a
      class of MGEs that have been found in most eukaryotic genomes, sometimes in
      extremely high numbers. In this article, we present a computational tool, MGEScan
      non-LTR, for the identification of non-LTR retrotransposons in genomic sequences,
      following a computational approach inspired by a generalized hidden Markov model
      (GHMM). Three different states represent two different protein domains and inter
      domain linker regions encoded in the non-LTR retrotransposons, and their scores
      are evaluated by using profile hidden Markov models (for protein domains) and
      Gaussian Bayes classifiers (for linker regions), respectively. In order to
      classify the non-LTR retrotransposons into one of the 12 previously characterized
      clades using the same model, we defined separate states for different clades.
      MGEScan-non-LTR was tested on the genome sequences of four eukaryotic organisms,
      Drosophila melanogaster, Daphnia pulex, Ciona intestinalis and Strongylocentrotus
      purpuratus. For the D. melanogaster genome, MGEScan-non-LTR found all known 'full
      length' elements and simultaneously classified them into the clades CR1, I,
      Jockey, LOA and R1. Notably, for the D. pulex genome, in which no non-LTR
      retrotransposon has been annotated, MGEScan-non-LTR found a significantly larger
      number of elements than did RepeatMasker, using the current version of the
      RepBase Update library. We also identified novel elements in the other two
      genomes, which have only been partially studied for non-LTR retrotransposons.

PMID- 19762482
TI  - Translesion DNA synthesis-assisted non-homologous end-joining of complex double
      strand breaks prevents loss of DNA sequences in mammalian cells.
AB  - Double strand breaks (DSB) are severe DNA lesions, and if not properly repaired,
      may lead to cell death or cancer. While there is considerable data on the repair
      of simple DSB (sDSB) by non-homologous end-joining (NHEJ), little is known about
      the repair of complex DSBs (cDSB), namely breaks with a nearby modification,
      which precludes ligation without prior processing. To study the mechanism of cDSB
      repair we developed a plasmid-based shuttle assay for the repair of a defined
      site-specific cDSB in cultured mammalian cells. Using this assay we found that
      repair efficiency and accuracy of a cDSB with an abasic site in a 5' overhang was
      reduced compared with a sDSB. Translesion DNA synthesis (TLS) across the abasic
      site located at the break prevented loss of DNA sequences, but was highly
      mutagenic also at the template base next to the abasic site. Similar to sDSB
      repair, cDSB repair was totally dependent on XrccIV, and altered in the absence
      of Ku80. In contrast, Artemis appears to be specifically involved in cDSB repair.
      These results may indicate that mammalian cells have a damage control strategy,
      whereby severe deletions are prevented at the expense of the less deleterious
      point mutations during NHEJ.

PMID- 19762483
TI  - Academic difficulty and program-level variables predict performance on the
      National Physical Therapy Examination for licensure: a population-based cohort
      study.
AB  - BACKGROUND: Several factors have been shown to influence first-time pass rates on
      the National Physical Therapy Examination (NPTE). It is unclear to what extent
      academic difficulty experienced by students in a physical therapist education
      program may affect NPTE pass rates. The effects of institutional status (public
      or private) and Carnegie Classification on NPTE pass rates also are unknown.
      OBJECTIVE: The aim of this study was to quantify the odds of failure on the NPTE
      for students experiencing academic difficulty and for institutional status and
      Carnegie Classification. DESIGN: This investigation was a retrospective
      population-based cohort study. METHODS: Quota sampling was used to recruit a
      random sample of 20 professional physical therapist education programs across the
      United States. Individual student demographic, preadmission, and academic
      performance data were collected, as were data on program-level variables and data
      indicating pass/fail performance on the NPTE. A generalized linear mixed-effects
      logistic regression model was used to adjust for confounding factors and to
      describe relationships among the key predictor variables-academic difficulty,
      institutional status, and Carnegie Classification-and the dependent variable,
      NPTE performance. RESULTS: Academic difficulty during a student's professional
      training was an independent predictor for NPTE failure. The odds of students who
      had academic difficulty (relative to students who did not experience academic
      difficulty) failing the NPTE were 5.89 (95% confidence interval=4.06-8.93). The
      odds of NPTE failure also varied depending on institutional status and Carnegie
      Classification. LIMITATIONS: The findings related to Carnegie Classification and
      institutional status should be considered preliminary. CONCLUSIONS: Student
      performance on the NPTE was influenced by multiple factors, but the most
      important, potentially modifiable risk factor for poor NPTE performance likely is
      academic difficulty during professional training.

PMID- 19762484
TI  - Associations of supported treadmill stepping with walking attainment in preterm
      and full-term infants.
AB  - BACKGROUND: Treadmill training in supported stepping has been used as part of
      rehabilitation programs for children with neurodevelopmental problems to
      facilitate earlier onset of walking. However, information concerning the
      developmental continuity between supported stepping and walking is limited.
      OBJECTIVE: The aims of this study were to longitudinally examine supported
      stepping in preterm and full-term infants and to explore the step parameters
      associated with walking attainment. DESIGN: A cohort study with a longitudinal
      follow-up design was used. METHODS: Twenty-nine preterm infants and 20 full-term
      infants were examined bimonthly with supported stepping on a treadmill from 7
      months of age until walking attainment or 18 months of corrected age. The
      associations between step variables and walking outcome were examined using Cox
      proportional hazard regression and logistic regression. RESULTS: Walking
      attainment for preterm infants was later than for full-term infants (median =
      12.8 versus 11 months, respectively). The percentage of alternating steps, hip
      knee correlation, hip-ankle correlation, and asymmetry ratio (AR) of stance time
      of stepping movement from 7 to 9 months of corrected age were found to be
      associated with age of walking attainment in all infants. Manifestation of at
      least 3 of 4 step features (ie, > or = 80% alternating steps, < or = .37 hip-knee
      correlation, > or = .73 hip-ankle correlation, and < or = 1.40 AR of stance time)
      at 7 months predicted walking attainment prior to 11 months of corrected age
      (accuracy = 75%-77%). Failure to achieve such competencies at 7 or 9 months of
      corrected age was predictive of failure in walking attainment by 15 months
      (accuracy = 72%-98%). Limitations The limitations of this study included a small
      sample size and commencement of stepping assessment as early as 7 months of
      corrected age. CONCLUSIONS: The emergence of walking may involve cooperation of
      alternating pattern generation, interjoint coordination, and interlimb
      coordination in supported stepping in preterm and full-term infants. The
      identified step predictors may assist clinicians in designing appropriate
      treadmill training programs for those infants with delayed walking.

PMID- 19762485
TI  - Diverse marrow stromal cells protect CLL cells from spontaneous and drug-induced
      apoptosis: development of a reliable and reproducible system to assess stromal
      cell adhesion-mediated drug resistance.
AB  - Marrow stromal cells (MSCs) provide important survival and drug resistance
      signals to chronic lymphocytic leukemia (CLL) cells, but current models to
      analyze CLL-MSC interactions are heterogeneous. Therefore, we tested different
      human and murine MSC lines and primary human MSCs for their ability to protect
      CLL cells from spontaneous and drug-induced apoptosis. Our results show that both
      human and murine MSCs are equally effective in protecting CLL cells from
      fludarabine-induced apoptosis. This protective effect was sustained over a wide
      range of CLL-MSC ratios (5:1 to 100:1), and the levels of protection were
      reproducible in 4 different laboratories. Human and murine MSCs also protected
      CLL cells from dexamethasone- and cyclophosphamide-induced apoptosis. This
      protection required cell-cell contact and was virtually absent when CLL cells
      were separated from the MSCs by micropore filters. Furthermore, MSCs maintained
      Mcl-1 and protected CLL cells from spontaneous and fludarabine-induced Mcl-1 and
      PARP cleavage. Collectively, these studies define common denominators for CLL
      cocultures with MSCs. They also provide a reliable, validated tool for future
      investigations into the mechanism of MSC-CLL cross talk and for drug testing in a
      more relevant fashion than the commonly used suspension cultures.

PMID- 19762486
TI  - CD56+ human blood dendritic cells effectively promote TH1-type gammadelta T-cell
      responses.
AB  - CD56+ human dendritic cells (DCs) have recently been shown to differentiate from
      monocytes in response to GM-CSF and type 1 interferon in vitro. We show here that
      CD56+ cells freshly isolated from human peripheral blood contain a substantial
      subset of CD14+CD86+HLA-DR+ cells, which have the appearance of intermediate
      sized lymphocytes but spontaneously differentiate into enlarged DC-like cells
      with substantially increased HLA-DR and CD86 expression or into fully mature
      CD83+ DCs in response to appropriate cytokines. Stimulation of CD56+ cells
      containing both DCs and abundant gammadelta T cells with zoledronate and
      interleukin-2 (IL-2) resulted in the rapid expansion of gammadelta T cells as
      well as in IFN-gamma, TNF-alpha, and IL-1beta but not in IL-4, IL-10, or IL-17
      production. IFN-gamma, TNF-alpha, and IL-1beta production were almost completely
      abolished by depleting CD14+ cells from the CD56+ subset before stimulation.
      Likewise, depletion of CD14+ cells dramatically impaired gammadelta T-cell
      expansion. IFN-gamma production could also be blocked by neutralizing the effects
      of endogenous IL-1beta and TNF-alpha. Conversely, addition of recombinant IL
      1beta, TNF-alpha, or both further enhanced IFN-gamma production and strongly up
      regulated IL-6 production. Our data indicate that CD56+ DCs from human blood are
      capable of stimulating CD56+ gammadelta T cells, which may be harnessed for
      immunotherapy.

PMID- 19762487
TI  - Generation of CD8+ T cell-mediated immunity against idiotype-negative lymphoma
      escapees.
AB  - We investigated the ability of CpG-oligodeoxynucleotide to generate an anti-tumor
      CD8+ T-cell immune response and to synergize with passive antibody therapy. For
      these studies, we generated an antibody against the idiotype on the A20 B-cell
      lymphoma line. This antibody caused the regression of established tumors, but
      ultimately the tumors relapsed. The escaping surface IgG-negative tumor cells
      were resistant to both antibody-dependent cellular cytotoxicity and signaling
      induced cell death. Addition of intratumoral CpG to antibody therapy cured large
      established tumors and prevented the occurrence of tumor escapees. The failure of
      the combination therapy in mice deficient for CD8+ T cells demonstrates the
      critical role of CD8+ T cells in tumor eradication. When mice were inoculated
      with 2 tumors and treated systemically with antibody followed by intratumoral CpG
      in just one tumor, both tumors regressed, indicating that a systemic immune
      response was generated. Although antibody therapy can eliminate tumor cells
      bearing the target antigen, it frequently selects for antigen loss variants.
      However, when a poly-specific T-cell response was generated against the tumor by
      intratumoral CpG, even large established tumors were cured. Such an immune
      response can prevent the emergence of antibody selected tumor escapees and
      provide long-lasting tumor protection.

PMID- 19762488
TI  - GM-CSF and IL-4 induce dendritic cell differentiation and disrupt
      osteoclastogenesis through M-CSF receptor shedding by up-regulation of TNF-alpha
      converting enzyme (TACE).
AB  - Monocytes give rise to macrophages, osteoclasts (OCs), and dendritic cells (DCs).
      Macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear
      factor-kappaB (RANK) ligand induce OC differentiation from monocytes, whereas
      granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL
      4) trigger monocytic differentiation into DCs. However, regulatory mechanisms for
      the polarization of monocytic differentiation are still unclear. The present
      study was undertaken to clarify the mechanism of triggering the deflection of OC
      and DC differentiation from monocytes. GM-CSF and IL-4 abolished monocytic
      differentiation into OCs while inducing DC differentiation even in the presence
      of M-CSF and RANK ligand. GM-CSF and IL-4 in combination potently up-regulate
      tumor necrosis factor-alpha (TNF-alpha) converting enzyme (TACE) and activity in
      monocytes, causing ectodomain shedding of M-CSF receptor, resulting in the
      disruption of its phosphorylation by M-CSF as well as the induction of
      osteoclastogenesis from monocytes by M-CSF and RANK ligand. Interestingly, TACE
      inhibition robustly causes the resumption of the surface expression of M-CSF
      receptor on monocytes, facilitating M-CSF-mediated phosphorylation of M-CSF
      receptor and macrophage/OC differentiation while impairing GM-CSF- and IL-4
      mediated DC differentiation from monocytes. These results reveal a novel
      proteolytic regulation of M-CSF receptor expression in monocytes to control M-CSF
      signaling and monocytic differentiation into macrophage/OC-lineage cells or DCs.

PMID- 19762489
TI  - Surprising results following conditional podocyte inactivation.

PMID- 19762490
TI  - More evidence that cystatin C predicts mortality better than creatinine.

PMID- 19762491
TI  - IL-18 and urinary NGAL predict dialysis and graft recovery after kidney
      transplantation.
AB  - Current methods for predicting graft recovery after kidney transplantation are
      not reliable. We performed a prospective, multicenter, observational cohort study
      of deceased-donor kidney transplant patients to evaluate urinary neutrophil
      gelatinase-associated lipocalin (NGAL), IL-18, and kidney injury molecule-1 (KIM
      1) as biomarkers for predicting dialysis within 1 wk of transplant and subsequent
      graft recovery. We collected serial urine samples for 3 d after transplant and
      analyzed levels of these putative biomarkers. We classified graft recovery as
      delayed graft function (DGF), slow graft function (SGF), or immediate graft
      function (IGF). Of the 91 patients in the cohort, 34 had DGF, 33 had SGF, and 24
      had IGF. Median NGAL and IL-18 levels, but not KIM-1 levels, were statistically
      different among these three groups at all time points. ROC curve analysis
      suggested that the abilities of NGAL or IL-18 to predict dialysis within 1 wk
      were moderately accurate when measured on the first postoperative day, whereas
      the fall in serum creatinine (Scr) was not predictive. In multivariate analysis,
      elevated levels of NGAL or IL-18 predicted the need for dialysis after adjusting
      for recipient and donor age, cold ischemia time, urine output, and Scr. NGAL and
      IL-18 quantiles also predicted graft recovery up to 3 mo later. In summary,
      urinary NGAL and IL-18 are early, noninvasive, accurate predictors of both the
      need for dialysis within the first week of kidney transplantation and 3-mo
      recovery of graft function.

PMID- 19762492
TI  - Donor age and renal P-glycoprotein expression associate with chronic histological
      damage in renal allografts.
AB  - The contributions of donor kidney quality (partially determined by donor age),
      allograft rejection, and calcineurin inhibitor nephrotoxicity on the progression
      of histologic damage of renal allografts are not completely defined. Moreover,
      the determinants of individual susceptibility to calcineurin inhibitor
      nephrotoxicity are not known but may include variability in drug transport and
      metabolism. In a prospective cohort of 252 adult renal allograft recipients
      treated with a combination of tacrolimus, mycophenolate mofetil, and
      corticosteroids, we studied 744 renal allograft biopsies obtained regularly from
      time of transplantation for 3 yr. We assessed determinants of histologic
      evolution, including tacrolimus exposure, renal P-glycoprotein (ABCB1)
      expression, and polymorphisms in the CYP3A4, CYP3A5, and ABCB1 genes. Within the
      first 3 yr after transplantation, we noted a progressive increase in interstitial
      fibrosis, tubular atrophy, glomerulosclerosis, and vascular intimal thickening.
      Older donor age, absence of P-glycoprotein expression at the apical membrane of
      tubular epithelial cells, and combined donor-recipient homozygosity for the
      C3435T variant in ABCB1 significantly associated with increased susceptibility to
      chronic allograft damage independent of graft quality at implantation. Changes in
      graft function over time reflected these associations with donor age and ABCB1
      polymorphisms, but it was acute T cell-mediated and antibody-mediated rejection
      that determined early graft survival. In conclusion, the effects of older donor
      age reach beyond the quality of the allograft at implantation and continue to be
      important for histologic evolution in the posttransplantation period. In
      addition, ABCB1 genotype and expression of P-glycoprotein in renal tubular
      epithelial cells determine susceptibility to chronic tubulointerstitial damage of
      transplanted kidneys.

PMID- 19762494
TI  - Planar cell polarity and the kidney.
AB  - Planar cell polarity (PCP) is a form of spatial organization in tissue that was
      first described in Drosophila melanogaster. PCP plays a critical conserved role
      in several aspects of mammalian development. Exciting data implicate PCP in
      normal kidney development and suggest the loss of oriented cell division and
      convergent extension downstream of defective PCP signaling lead to cystic kidney
      disease in mouse models. In this review, I first cover the current knowledge of
      PCP signaling in invertebrate and vertebrate models and then explore how loss of
      PCP might underlie some forms of cystic kidney disease.

PMID- 19762493
TI  - Proliferation and migration of label-retaining cells of the kidney papilla.
AB  - The kidney papilla contains a population of cells with several characteristics of
      adult stem cells, including the retention of proliferation markers during long
      chase periods (i.e., they are label-retaining cells [LRCs]). To determine whether
      the papillary LRCs generate new cells in the normal adult kidney, we examined
      cell proliferation throughout the kidney and found that the upper papilla is a
      site of enhanced cell cycling. Using genetically modified mice that conditionally
      expressed green fluorescence protein fused to histone 2B, we observed that the
      LRCs of the papilla proliferated only in its upper part, where they associate
      with "chains" of cycling cells. The papillary LRCs decreased in number with age,
      suggesting that the cells migrated to the upper papilla before entering the cell
      cycle. To test this directly, we marked papillary cells with vital dyes in vivo
      and found that some cells in the kidney papilla, including LRCs, migrated toward
      other parts of the kidney. Acute kidney injury enhanced both cell migration and
      proliferation. These results suggest that during normal homeostasis, LRCs of the
      kidney papilla (or their immediate progeny) migrate to the upper papilla and form
      a compartment of rapidly proliferating cells, which may play a role in repair
      after ischemic injury.

PMID- 19762495
TI  - Six-month prophylaxis is cost effective in transplant patients at high risk for
      cytomegalovirus infection.
AB  - The risk of late-onset cytomegalovirus (CMV) infection remains a concern in
      seronegative kidney and/or pancreas transplant recipients of seropositive organs
      despite the use of antiviral prophylaxis. The optimal duration of prophylaxis is
      unknown. We studied the cost effectiveness of 6- versus 3-mo prophylaxis with
      valganciclovir. A total of 222 seronegative recipients of seropositive kidney
      and/or pancreas transplants received valganciclovir prophylaxis for either 3 or 6
      mo during two consecutive time periods. We assessed the incidence of CMV
      infection and disease 12 mo after completion of prophylaxis and performed cost
      effectiveness analyses. The overall incidence of CMV infection and disease was
      26.7% and 24.4% in the 3-mo group and 20.9% and 12.1% in the 6-mo group,
      respectively. Six-month prophylaxis was associated with a statistically
      significant reduction in risk for CMV disease (HR, 0.35; 95% CI, 0.17 to 0.72),
      but not infection (HR, 0.65; 95% CI, 0.37 to 1.14). Cost-effectiveness analyses
      showed that 6-mo prophylaxis combined with a one-time viremia determination at
      the end of the prophylaxis period incurred an incremental cost of $34,362 and
      $16,215 per case of infection and disease avoided, respectively, and $8,304 per
      one quality adjusted life-year gained. Sensitivity analyses supported the cost
      effectiveness of 6-mo prophylaxis over a wide range of valganciclovir and
      hospital costs, as well as variation in the incidence of CMV disease. In summary,
      6-mo prophylaxis with valganciclovir combined with a one-time determination of
      viremia is cost effective in reducing CMV infection and disease in seronegative
      recipients of seropositive kidney and/or pancreas transplants.

PMID- 19762496
TI  - Cost-effectiveness of aliskiren in type 2 diabetes, hypertension, and
      albuminuria.
AB  - The Aliskiren in the Evaluation of Proteinuria in Diabetes (AVOID) trial
      demonstrated that adding aliskiren, an oral direct renin inhibitor, at a dosage
      of 300 mg/d to the highest approved dosage of losartan and optimal
      antihypertensive therapy reduces albuminuria over 6 mo among patients with type 2
      diabetes, hypertension, and albuminuria. The cost-effectiveness of this therapy,
      however, is unknown. Here, we used a Markov model to project progression to ESRD,
      life years, quality-adjusted life years, and lifetime costs for aliskiren plus
      losartan versus losartan. We used data from the AVOID study and the Irbesartan in
      Diabetic Nephropathy Trial (IDNT) to estimate probabilities of progression of
      renal disease. We estimated probabilities of mortality for ESRD and other
      comorbidities using data from the US Renal Data System, US Vital Statistics, and
      published studies. We based pharmacy costs on wholesale acquisition costs and
      based costs of ESRD and transplantation on data from the US Renal Data System. We
      found that adding aliskiren to losartan increased time free of ESRD, life
      expectancy, and quality-adjusted life expectancy by 0.1772, 0.1021, and 0.0967
      yr, respectively. Total expected lifetime health care costs increased by $2952,
      reflecting the higher pharmacy costs of aliskiren and losartan ($7769), which
      were partially offset by savings in costs of ESRD ($4860). We estimated the cost
      effectiveness of aliskiren to be $30,500 per quality-adjusted life year gained.
      In conclusion, adding aliskiren to losartan and optimal therapy in patients with
      type 2 diabetes, hypertension, and albuminuria may be cost-effective from a US
      health care system perspective.

PMID- 19762497
TI  - Method of glomerular filtration rate estimation affects prediction of mortality
      risk.
AB  - Decreased kidney function, determined using a serum creatinine-based estimation
      of GFR, is associated with a higher risk for mortality from cardiovascular
      disease. Equations incorporating cystatin C improve the estimation of GFR, but
      whether this improves the prediction of risk for mortality is unknown. We
      measured cystatin C on 6942 adult participants in the Third National Health and
      Nutrition Examination Survey Linked Mortality File, including all participants
      who had high serum creatinine (>1.2 mg/dl for men; >1.0 mg/dl for women) or were
      older than 60 yr and 25% random sample of participants who were younger than 60
      yr. We estimated GFR using equations that included standardized serum creatinine,
      cystatin C, or both. Participant data were linked to the National Death Index. A
      total of 1573 (22.7%) deaths (713 deaths from cardiovascular disease) occurred
      during a median of 8 yr. Lower estimated GFR based on cystatin C was strongly
      associated with higher risk for overall and cardiovascular mortality across the
      range of normal to moderately decreased estimated GFR. Creatinine-based estimates
      of GFR resulted in weaker associations, with the association between estimated
      GFR and all-cause mortality reversed at higher levels of estimated GFR. An
      equation using both creatinine and cystatin C (in addition to age, race, and
      gender) resulted in weaker associations than equations using only cystatin C
      (with or without age, race, and gender). In conclusion, despite better
      performance in terms of estimating GFR, equations based on both cystatin C and
      creatinine do not predict mortality as well as equations based on cystatin C
      alone.

PMID- 19762498
TI  - New complement regulator exposed.

PMID- 19762499
TI  - Out of this nettle, danger, we must pluck this flower, safety.

PMID- 19762500
TI  - T(11q23): brand necessary.

PMID- 19762501
TI  - The lymphatic tissue microenvironments in chronic lymphocytic leukemia: in vitro
      models and the significance of CD40-CD154 interactions.

PMID- 19762504
TI  - Clinical relevance of brown snake (Pseudonaja spp) factor V escaping hemostatic
      regulation.

PMID- 19762505
TI  - Reduced-intensity conditioning allogeneic stem cell transplantation in HIV
      patients with hematologic malignancies: yes, we can.

PMID- 19762506
TI  - Rapidly declining unilateral hearing within 1 month in a newborn with internal
      auditory canal stenosis and facial palsy.
AB  - Most newborns with congenital unilateral facial palsy are expected to recover;
      however, when a patient has hearing loss, underlying developmental ear structure
      abnormalities should be investigated, particularly when the patient has internal
      auditory canal stenosis, which is rarely reported in newborns. All cases of
      internal auditory canal stenosis are accompanied by concomitant unilateral or
      bilateral hearing loss, but none with progressive hearing loss has been reported.
      We present the case of a newborn with rapidly declining hearing in the left ear
      within 1 month after birth. The hearing decline was associated with unilateral
      facial palsy. Using high-resolution computed tomography (CT) of the temporal
      bone, we diagnosed the patient with congenital internal auditory canal stenosis.
      This is the first case detected with progressive hearing loss after birth, which
      implies that prompt diagnosis and early habilitation are warranted, even when the
      hearing loss is initially mild.

PMID- 19762507
TI  - Cognitive function and event-related potentials in children with type 1 diabetes
      mellitus.
AB  - Type 1 diabetes mellitus is associated with cognitive changes, but the extent of
      cognition decline depends on age at onset, duration of diabetes, and occurrence
      of attacks of hypoglycemia or ketoacidosis. This study was designed to assess
      cognitive function in a group of children with type 1 diabetes mellitus. A total
      of 40 diabetic children were recruited from the pediatric department of Assiut
      University Hospital, Egypt. Forty healthy children matched for age, sex, and
      socioeconomic status were chosen as controls for comparison. Cognition was
      assessed using Stanford-Binet and event-related potentials tests. Compared to the
      control group, patients reported a significant reduction in intelligent quotient,
      comprehension, abstract visual reasoning, quantitative reasoning, bead memory,
      and total short memory testing for cognitive functions. Prolonged N1, P200, N2,
      and P300 latencies and reduced P300-N2 amplitude were reported. Significant
      negative correlations were identified in most studied cognitive functions and
      ketoacidosis or family history of diabetes mellitus.

PMID- 19762508
TI  - XBP-1 deficiency in the nervous system protects against amyotrophic lateral
      sclerosis by increasing autophagy.
AB  - Mutations in superoxide dismutase-1 (SOD1) cause familial amyotrophic lateral
      sclerosis (fALS). Recent evidence implicates adaptive responses to endoplasmic
      reticulum (ER) stress in the disease process via a pathway known as the unfolded
      protein response (UPR). Here, we investigated the contribution to fALS of X-box
      binding protein-1 (XBP-1), a key UPR transcription factor that regulates genes
      involved in protein folding and quality control. Despite expectations that XBP-1
      deficiency would enhance the pathogenesis of mutant SOD1, we observed a dramatic
      decrease in its toxicity due to an enhanced clearance of mutant SOD1 aggregates
      by macroautophagy, a cellular pathway involved in lysosome-mediated protein
      degradation. To validate these observations in vivo, we generated mutant SOD1
      transgenic mice with specific deletion of XBP-1 in the nervous system. XBP-1
      deficient mice were more resistant to developing disease, correlating with
      increased levels of autophagy in motoneurons and reduced accumulation of mutant
      SOD1 aggregates in the spinal cord. Post-mortem spinal cord samples from patients
      with sporadic ALS and fALS displayed a marked activation of both the UPR and
      autophagy. Our results reveal a new function of XBP-1 in the control of autophagy
      and indicate critical cross-talk between these two signaling pathways that can
      provide protection against neurodegeneration.

PMID- 19762509
TI  - Transcription factor choice in the Hippo signaling pathway: homothorax and yorkie
      regulation of the microRNA bantam in the progenitor domain of the Drosophila eye
      imaginal disc.
AB  - The accurate control of cell proliferation and survival is critical for animal
      development. The Hippo tumor suppressor pathway regulates both of these
      parameters by controlling the nuclear availability of the transcriptional
      coactivator Yorkie (Yki), which regulates downstream target genes together with
      Scalloped (Sd), a DNA-binding protein. Here we provide evidence that Yki can also
      regulate target genes in conjunction with Homothorax (Hth) and Teashirt (Tsh),
      two DNA-binding transcription factors expressed in the uncommitted progenitor
      cells of the Drosophila eye imaginal disc. Clonal analyses demonstrate that Hth
      and Tsh promote cell proliferation and protect eye progenitor cells from
      apoptosis. Genetic epistasis experiments suggest that Hth and Tsh execute these
      functions with Yki, in part by up-regulating the microRNA bantam. A physical
      interaction between Hth and Yki can be detected in cell culture, and we show that
      Hth and Yki are bound to a DNA sequence approximately 14 kb upstream of the
      bantam hairpin in eye imaginal disc cells, arguing that this regulation is
      direct. These data suggest that the Hippo pathway uses different DNA-binding
      transcription factors depending on the cellular context. In the eye disc, Hth and
      Tsh provide spatial information to this pathway, promoting cell proliferation and
      survival in the progenitor domain.

PMID- 19762511
TI  - An update on twenty years of anemia management with erythropoiesis-stimulating
      agents in nephrology and oncology/hematology.

PMID- 19762510
TI  - An inducible change in Fox-1/A2BP1 splicing modulates the alternative splicing of
      downstream neuronal target exons.
AB  - Neuronal depolarization and CaM kinase IV signaling alter the splicing of
      multiple exons in transcripts for ion channels, neurotransmitter receptors, and
      other synaptic proteins. These splicing changes are mediated in part by special
      CaM kinase-responsive RNA elements, within or adjacent to exons that are
      repressed in the initial phase of chronic depolarization. The splicing of many
      neuronal transcripts is also regulated by members of the Fox (Feminizing gene on
      X) protein family, and these Fox targets are also often proteins affecting
      synaptic activity. We show that Fox-1/Ataxin 2-Binding Protein 1 (A2BP1), a
      protein implicated in a variety of neurological diseases, can counteract the
      effects of chronic depolarization on splicing. We find that exon 19 of Fox-1 is
      itself repressed by depolarization. Fox-1 transcripts missing exon 19 encode a
      nuclear isoform of Fox-1 that progressively replaces the cytoplasmic Fox-1
      isoform as cells are maintained depolarizing media. The resulting increase in
      nuclear Fox-1 leads to the reactivation of many Fox-1 target exons, including
      exon 5 of the NMDA receptor 1, that were initially repressed by the high-KCl
      medium. These results reveal a novel mechanism for the slow modulation of
      splicing as cells adapt to chronic stimuli: The subcellular localization of a
      splicing regulator is controlled through its own alternative splicing.

PMID- 19762512
TI  - Update on erythropoiesis-stimulating agents and clinical trials in oncology.
AB  - Anemia commonly occurs among cancer patients receiving chemotherapy. In these
      patients, erythropoiesis-stimulating agents (ESAs) are effective in managing
      anemia but there is an increased risk for thrombovascular events. In more recent
      randomized clinical trials, there have been differing results regarding the
      impact of ESAs on overall survival and mortality. The balance between studies
      that show higher ESA-associated mortality and those that don't show ESA
      associated mortality is examined in this review. This review discusses where we
      stand today on anemia management in cancer patients. Preliminary results from a
      recent independent patient data meta-analysis for on-study deaths and overall
      survival in patients receiving chemotherapy (the only oncology population for
      which ESA treatment is currently indicated) showed no statistically significant
      difference between the ESA and control groups (on-study deaths hazard ratio [HR],
      1.10; 95% confidence interval [CI], 0.98-1.24; overall survival HR, 1.04; 95% CI,
      0.97-1.11, compared with controls). Possible factors that could influence study
      results are discussed in this review. There are no convincing data to support ESA
      induced tumor stimulation in patients. ESAs decrease RBC transfusion needs and
      sustain targeted hemoglobin levels, and this ESA response does not significantly
      impact overall survival or mortality when ESAs are used within guidelines and
      labeling. However, based on the currently available data and meta-analysis, the
      use of ESAs has to be carefully balanced against any possible risk for higher
      mortality.

PMID- 19762513
TI  - Update on anemia management in nephrology, including current guidelines on the
      use of erythropoiesis-stimulating agents and implications of the introduction of
      "biosimilars".
AB  - Several million patients with chronic kidney disease (CKD) have benefited from
      the use of erythropoiesis-stimulating agents (ESAs) to correct severe anemia.
      However, mortality data now suggest that treating CKD patients to achieve a
      hemoglobin (Hb) level >13 g/dl can be harmful. For levels of 11.5-13 g/dl, there
      is no evidence of either harm or benefit compared with a lower Hb level. Quality
      of life studies are variable in quality but do suggest superior outcomes and
      functional status. In the 9 years following 1997, the target Hb level recommended
      by international guidelines tended to increase, especially for patients without
      accompanying cardiovascular disease. However, strangely enough, the most recent
      target level of the Kidney Disease Outcomes Quality Initiative is 11-12 g/dl,
      which is exactly the range advocated by the same group a decade earlier. The
      relative importance of quality of life compared with other outcomes, the use of
      iron, and the impact of venous thrombotic events continue to be debated. In
      addition, new issues have arisen from the introduction of "biosimilar"
      erythropoietins, biopharmaceuticals that refer to the existing agents and are
      submitted for marketing authorization after the existing agents' protection
      expires. Biosimilars can resemble the agents on which they are modeled but cannot
      fully copy their properties. The complexity in molecular structure, the possible
      presence of impurities (which may include bacterial endotoxins), and the inherent
      immunogenicity of such agents have required authorities to develop a
      sophisticated regulatory framework.

PMID- 19762514
TI  - Iron metabolism, iron deficiency, thrombocytosis, and the cardiorenal anemia
      syndrome.
AB  - In treating moderate to severe anemia of chronic kidney disease (CKD), oral iron
      is effective only in a minority of nondialysis patients. Intravenous iron is more
      effective and can raise levels of hemoglobin even without the use of
      erythropoiesis-stimulating agents (ESAs). Unfortunately, the current assays of
      iron status that are presently widely available are not especially helpful in
      predicting response. In patients on dialysis, i.v. iron is effective over a wide
      range of serum ferritin from <100 ng/ml to 800 ng/ml. None of the three available
      randomized controlled trials comparing oral with i.v. iron showed evidence of
      nephrotoxicity caused by i.v. iron. Iron deficiency is a risk factor for
      thrombocytosis and should, wherever possible, be avoided. Optimal
      coadministration of iron may reduce the risk for ESA-driven cardiovascular
      events. Increased total body iron stores (imperfectly reflected by serum ferritin
      levels in CKD) do not appear to be related to such events or hospitalization in
      CKD; it is unclear what other risk factors and mechanisms need to be considered.
      In the appreciable proportion of patients with both renal and cardiac
      dysfunction, management is further complicated by a vicious circle (which can be
      characterized as cardiorenal anemia syndrome) in which CKD, heart failure, and
      anemia exacerbate each other. In such patients, correction of anemia appears to
      improve cardiac function and quality of life without a greater risk for adverse
      events.

PMID- 19762515
TI  - Examining the involvement of erythropoiesis-stimulating agents in tumor
      proliferation (erythropoietin receptors, receptor binding, signal transduction),
      angiogenesis, and venous thromboembolic events.
AB  - Safety concerns have arisen about the possibility of erythropoiesis-stimulating
      agents (ESAs) promoting tumor growth and increasing the incidence of venous
      thromboembolic events (VTEs). Because of the reported presence of erythropoietin
      receptors (EPORs) on tumor cells, it was questioned if ESAs had the potential for
      promoting tumor growth through stimulation of EPORs and tumor vessels and/or
      enhanced tumor oxygenation. Studies have shown that EPOR mRNA can be isolated
      from tumor cells, but the presence of EPOR protein has not yet been proven
      because of a lack of specific antibodies against EPORs. It is questionable
      whether EPORs on tumor cells are functional and there is no evidence that ESAs
      (within the approved indication in patients receiving chemotherapy) can stimulate
      EPORs on tumor cells in vivo. VTEs are frequent in cancer patients, resulting
      from the effects of malignant disease, cancer treatments, and comorbidities. VTEs
      are a leading cause of death in cancer patients. There are concerns about ESAs
      and a possible higher risk for VTEs and shorter survival in cancer patients. The
      higher risk for VTEs associated with ESAs appears to be a class effect, but the
      risk may be particularly pronounced when ESAs are used off label, as seen in
      clinical trials that targeted hemoglobin levels higher than those recommended by
      current ESA labeling and trials that enrolled patients who were not anemic at
      baseline. ESA treatment should be used within labeling confines.

PMID- 19762516
TI  - Anemia management in oncology and hematology.
AB  - Anemia is frequent in cancer patients and its incidence increases with
      chemotherapy. The probability of requiring transfusions also increases with
      chemotherapy. Anemia negatively impacts survival and accentuates fatigue in
      cancer patients. Cancer promotes inflammatory cytokine production, which
      suppresses erythropoiesis and erythropoietin (EPO) production. Erythropoiesis
      stimulating agents (ESAs) improve erythropoiesis and reduce transfusion needs in
      anemic cancer patients receiving chemotherapy. However, meta-analyses have shown
      an increased risk of thromboembolic (TE) events with ESA use during chemotherapy,
      but not increased on-study mortality or reduced overall survival. Three reasons
      have been proposed to explain why ESAs might have adverse effects in anemic
      cancer patients: tumor progression due to stimulation of tumor cell EPO
      receptors; increased risk of TE; and reduced survival. However, erythropoietin is
      not an oncogene, nor is the EPO receptor. It has also been demonstrated that
      erythropoietin does not stimulate tumor proliferation. Increased TE risk
      associated with ESAs is probably a consequence of increased blood viscosity due
      to excessive RBC mass elevation with concomitant plasma volume contraction,
      nitric oxide scavenging, and endothelial cell activation. Increased ESA dosing
      may also impact survival negatively because EPO contracts the plasma volume and
      stimulates inflammatory cytokine production independently of increasing
      erythropoiesis. Furthermore, transfusions themselves are associated with an
      increase in TE and plasma volume contraction, and these events are potentiated
      when ESAs are given with transfusions. An update on the management of anemia in
      oncology, the potential adverse events of ESAs, the benefits and risks of
      transfusions, and QoL are discussed in this paper.

PMID- 19762517
TI  - Is nephrology more at ease than oncology with erythropoiesis-stimulating agents?
      Treatment guidelines and an update on benefits and risks.
AB  - Erythropoiesis-stimulating agents (ESAs), which promote RBC production, have been
      extensively used to reduce transfusion requirements and improve quality of life
      (QoL) in both cancer patients and those with chronic kidney disease (CKD).
      However, the likelihood of response and duration of treatment differ in the two
      settings. In renal anemia, ESAs act straightforwardly as hormone-replacement
      therapy. The anemia of cancer, however, relates not to a lack of endogenous
      erythropoietin production but to diverse aspects of the disease (including a
      relevant inflammatory component) and chemotherapy. Response to ESAs is slower and
      less certain than in nephrology. In both settings, early studies showed that
      reversal of severe anemia was accompanied by substantial improvement in QoL.
      However, again in both settings, subsequent studies indicated that efforts to
      normalize hemoglobin might worsen outcome. In the context of cancer, this concern
      was reinforced by the suggestion that malignant cells had erythropoietin
      receptors and that its administration might therefore accelerate tumor growth,
      and moreover that cancer patients are more susceptible to venous thrombosis. The
      absence of these concerns for nephrologists, and their greater experience in
      managing ESAs and patients' iron status, may make them more at ease with ESAs
      than their counterparts in oncology. However, both groups of specialists have had
      to deal with reversals in recommended thresholds for intervention and
      restrictions imposed by regulatory authorities. In both specialties, the broad
      consensus now emerging is that the optimum balance of benefits and risks lies in
      using ESAs aimed at a hemoglobin level in the range of 11-12 g/dl, although for
      CKD patients there is still room for an individualized approach.

PMID- 19762518
TI  - Sex differences in sum scores may be hard to interpret: the importance of
      measurement invariance.
AB  - In most assessment instruments, distinct items are designed to measure a trait,
      and the sum score of these items serves as an approximation of an individual's
      trait score. In interpreting group differences with respect to sum scores, the
      instrument should measure the same underlying trait across groups (e.g.,
      male/female, young/old). Differences with respect to the sum score should
      accurately reflect differences in the latent trait of interest. A necessary
      condition for this is that the instrument is measurement invariant. In the
      current study, the authors illustrate a stepwise approach for testing measurement
      invariance with respect to sex in a four-item instrument designed to assess
      disordered eating behavior in a large epidemiological sample (1,195 men and 1,507
      women). This approach can be applied to other phenotypes for which group
      differences are expected. Any analysis of such variables may be subject to
      measurement bias if a lack of measurement invariance between grouping variables
      goes undetected.

PMID- 19762519
TI  - A review of the Minnesota Multiphasic Personality Inventory-Adolescent (MMPI-A)
      and the Millon Adolescent Clinical Inventory (MACI) with an emphasis on juvenile
      justice samples.
AB  - The Minnesota Multiphasic Personality Inventory-Adolescent (MMPI-A) and Millon
      Adolescent Clinical Inventory (MACI) are frequently used objective personality
      self-report measures. Given their widespread use, the purpose of the current
      study was to examine and compare the literature base for the two instruments. A
      comprehensive review of the literature was conducted between the years 1992 and
      2007 using the PsycINFO Database. Results indicate the publication of 277
      articles, books, book chapters, monographs, and dissertation abstracts on the
      MMPI-A. This was compared with the results of a comparable search for the MACI,
      which yielded 84 citations. The literature was further explored by determining
      the content of the topic areas addressed for both instruments. A particular focus
      was placed on the utility of the instruments with juvenile justice populations;
      scale means, standard deviations, and effect sizes calculated from this
      literature were examined. Results indicate that the use of the MMPI-A is
      supported by a substantial literature and a growing research base is also
      available for the MACI. Both instruments appear to provide useful results in
      juvenile justice settings.

PMID- 19762520
TI  - A psychometric examination of multidimensional inventory of black identity (MIBI)
      scores.
AB  - The factor structure of the Multidimensional Inventory of Black Identity (MIBI)
      was assessed in a sample of 272 African American college students using
      confirmatory and exploratory factor analyses. The fit indices from the
      confirmatory analyses did not support the seven-factor first-order model or two
      alternative higher-order models suggested by the developers, but yielded numerous
      recommendations for modifications. A post hoc exploratory factor analysis
      indicated that MIBI items were best represented by a five-factor structure.

PMID- 19762521
TI  - Systemic hypoxia affects exercise-mediated antitumor cytotoxicity of natural
      killer cells.
AB  - Natural killer cells (NKs) are important to the clearance of transformed cells.
      This investigation elucidates how systemic hypoxia influences mobilization of the
      NK subsets and cytotoxicity of NKs to nasopharyngeal carcinoma cells (NPCs)
      during exercise. Sixteen sedentary men performed six distinct experimental tests
      in an air-conditioned normobaric hypoxia chamber: high-intensity exercise [HE; up
      to maximal O(2) consumption (Vo(2 max))] under 21% O(2); moderate-intensity
      exercise (ME; 50% Vo(2 max) for 30 min) under 12%, 15%, and 21% O(2); and
      breathing 12% and 15% O(2) for 30 min at rest. The results demonstrated that 21%
      O(2) HE, but not ME, increased cellular perforin/granzyme B/interferon-gamma
      levels in NKs and interferon-gamma concentration in NK-NPC coincubation, and also
      promoted capacity of NKs to bind to NPCs and NK-induced CD95 expression and
      phosphatidylserine exposure of NPCs. However, the HE simultaneously increased
      percentages of the replicative senescent (CD57(+) and CD28(-)) NKs and the NKs
      with inhibitory receptors (KLRG1(+)) that entered the bloodstream from peripheral
      tissues. Breathing 12% and 15% O(2) at rest did not influence mobilization of NK
      subsets and cytotoxicity of NKs to NPCs. Although both 12% and 15% O(2) ME
      increased NK count, perforin/granzyme B/interferon-gamma levels, NK-NPC binding,
      and NK-induced CD95 expression and apoptosis of NPC, only 12% O(2) ME increased
      percentages of the NKs with CD57(+)/CD28(-)/KLRG1(+) in blood. Therefore, we
      conclude that systemic hypoxic exposure affects redistribution of NK subsets and
      anti-NPC cytotoxicity of NKs during exercise in a concentration-dependent manner.
      Moreover, exposure to 12% O(2) promotes the NK cytotoxicity with mobilizing the
      replicative senescent/inhibitory NKs into the bloodstream during ME.

PMID- 19762522
TI  - Evidence for dysanapsis using computed tomographic imaging of the airways in
      older ex-smokers.
AB  - We sought to determine the relationship between lung size and airway size in men
      and women of varying stature. We also asked if men and women matched for lung
      size would still have differences in airway size and if so where along the
      pulmonary airway tree would these differences exist. We used computed tomography
      to measure airway luminal areas of the large and central airways. We determined
      airway luminal areas in men (n = 25) and women (n = 25) who were matched for age,
      body mass index, smoking history, and pulmonary function and in a separate set of
      men (n = 10) and women (n = 11) who were matched for lung size. Men had greater
      values for the larger airways and many of the central airways. When male and
      female subjects were pooled there were significant associations between lung size
      and airway size. Within the male and female groups the magnitudes of these
      associations were decreased or nonsignificant. In males and females matched for
      lung size women had significantly smaller airway luminal areas. The larger
      conducting airways in females are significantly smaller than those of males even
      after controlling for lung size.

PMID- 19762523
TI  - Effect of contrasting physical exercise interventions on rapid force capacity of
      chronically painful muscles.
AB  - Rapid force capacity of chronically painful muscles is inhibited markedly more
      than maximal force capacity and is therefore relevant to assess in rehabilitation
      settings. Our objective was to investigate the effect of two contrasting types of
      physical exercise on rapid force capacity, as well as neural and muscular
      adaptations in women with chronic neck muscle pain. A group of employed women (n
      = 42) with a clinical diagnosis of trapezius myalgia participated in a 10-wk
      randomized controlled trial; specific strength training of the neck/shoulder
      muscles, general fitness training performed as leg-bicycling; or a reference
      intervention without physical activity. Maximal voluntary shoulder abductions
      were performed at static angles of 35 degrees and 115 degrees with simultaneous
      recording of electromyography (EMG) in the trapezius and deltoid. Maximal muscle
      strength and activation (peak torque and peak EMG) as well as rapid muscle
      strength and activation [rate of torque development (RTD) and rate of EMG rise]
      were subsequently determined. Trapezius muscle fiber characteristics were
      determined with ATPase histochemistry. Significant changes were observed only in
      the specific strength training group. Whereas peak torque increased 18-29% (P <
      0.01), RTD increased 61-115% (P < 0.001). Peak EMG and rate of EMG rise increased
      correspondingly (P < 0.05-0.001), and trapezius type II muscle fibers
      hypertrophied 20% (P < 0.001). In conclusion, rapid force capacity of chronically
      painful muscles is highly responsive to rehabilitation with specific strength
      training. The underlying mechanisms were related to both pain reduction and
      general neuromuscular adaptations to strength training. Potentially, the present
      method can be a useful clinical screening tool of muscle function in
      rehabilitation settings.

PMID- 19762524
TI  - Nicotinic acetylcholine receptors do not mediate excitatory transmission in young
      rat carotid body.
AB  - Carotid body chemoreceptors transduce a decrease in arterial oxygen tension into
      increased action potential (AP) activity on the sinus nerve, which increases the
      drive to breathe. The mechanism by which AP activity increases is unresolved, but
      acetylcholine (ACh), acting through nicotinic receptors, is postulated to be a
      major contributor to nerve excitation based partly on the demonstration that
      pharmacological antagonism of nicotinic receptors reduces the afferent nerve
      response in some studies. However, most previous studies relied on indirect
      measures of chemoreceptor activity or utilized a recording configuration that is
      sensitive to AP morphology in addition to AP frequency. In the present study,
      single-unit AP activity was recorded from the soma of rat chemoreceptor neurons
      in vitro. The nicotinic blocker mecamylamine (50 microM) ablated the excitatory
      actions of exogenous ACh and increased, rather than decreased, AP activity during
      moderate hypoxia. At higher dosage (500 microM) AP height was reduced, conduction
      velocity slowed, and conduction failure occurred, especially during hypoxia,
      producing the appearance of a decreased response to hypoxia. Recovery from
      mecamylamine block was slow (>10 min). In contrast to mecamylamine, suramin, a
      P2X receptor blocker, reversibly inhibited the response to hypoxia, suggesting
      relatively free diffusion of drugs to the glomus cell/nerve synaptic site. These
      results strongly suggest that ACh acting through nicotinic receptors does not
      mediate excitatory transmission in rat carotid body and that previous results
      demonstrating such a role may have been partially influenced by changes in AP
      morphology or conduction failure.

PMID- 19762525
TI  - Diabetic microangiopathy in the liver: an autopsy study of incidence and
      association with other diabetic complications.
AB  - Diabetic hepatosclerosis (DH) is a recently described form of diabetic
      microangiopathy with hepatic sinusoidal fibrosis and basement membrane deposition
      without cirrhosis. The objective was to investigate the frequency of DH and its
      correlation with other diabetic microangiopathic complications. Complete
      autopsies from 57 adults with diabetes were reviewed for liver pathology and
      other diabetic complications. Basement membrane deposition in the liver was
      highlighted using laminin and type IV collagen immunostains. Only 1 case of DH
      was identified. Other diabetic end-organ damage in this case included nodular
      glomerulosclerosis and hepatic hyaline arteriolosclerosis, which were the most
      severe in the series. DH is an uncommon pattern of liver disease in patients with
      diabetes and is associated with severe end-organ damage. This study supports the
      presumed vascular etiology of DH, confirms the rarity of the lesion, and supports
      the suggestion that it is usually accompanied by other end-organ damage.

PMID- 19762526
TI  - In situ evidence of KRAS amplification and association with increased p21 levels
      in non-small cell lung carcinoma.
AB  - Recent advances in the characterization of the lung cancer genome have suggested
      that KRAS may frequently be amplified, although little is known regarding the
      significance of this finding. This is in contrast with activating mutations of
      KRAS, which occur in approximately 20% of non-small cell lung carcinomas
      (NSCLCs). We used fluorescence in situ hybridization to provide direct evidence
      of KRAS amplification for the first time in clinical specimens. We detected
      amplification in 7 of 100 consecutive NSCLCs, with a concurrent activating KRAS
      mutation in 4 cases. KRAS amplification was associated with greater expression of
      p21 as assessed by quantitative immunohistochemical analysis (P = .015). Our data
      indicate that a sizable subgroup of NSCLCs harbor KRAS amplification, some of
      which also contain point mutations, and suggest that an increased KRAS copy
      number may drive p21 overexpression. KRAS amplification may define a unique
      clinicopathologic subset of NSCLCs with potentially altered responsiveness to
      targeted therapies.

PMID- 19762527
TI  - The assessment of specimens procured by endoscopic ampullectomy.
AB  - Endoscopic ampullectomy (EA) is increasingly used in the management of ampullary
      neoplasia. Although studies on the safety and efficacy of this procedure exist,
      no study has specifically addressed the histopathologic features of the
      specimens. We review our experience with 45 EA specimens assessed for the
      following: diagnosis, high-grade dysplasia (HGD), submucosal ampullary
      gland/ductule involvement, specimen integrity, and margin status. Familial
      adenomatous polyposis (FAP) status and the endoscopist's impression of
      completeness of removal were also ascertained. Previous biopsy diagnoses were
      compared with ampullectomy diagnoses, and histologic and clinical features were
      correlated with disease persistence. The histologic features of the ampullectomy
      specimens were as follows: diagnosis (no diagnostic abnormality, 3; reactive, 8;
      adenoma, 26; adenocarcinoma, 7; other, 1); HGD, 1; submucosal ampullary
      gland/ductule involvement, 20; specimen integrity (intact, 22; fragmented, 23);
      and margin status (positive, 20; negative, 2; could not be assessed, 12). Five
      patients had FAP, and EA was deemed complete in 21 (47%). The diagnostic
      agreement between preampullectomy biopsy and ampullectomy was 64%. Of the
      patients, 33 (73%) had documented persistent disease. None of the histologic or
      clinical features had a statistically significant relationship with disease
      persistence.

PMID- 19762528
TI  - Chromogenic in situ hybridization: a multicenter study comparing silver in situ
      hybridization with FISH.
AB  - Our purposes were to perform a robust assessment of a new HER2 chromogenic in
      situ hybridization test and report on concordance of silver in situ hybridization
      (SISH) data with fluorescence in situ hybridization (FISH) data and on
      intraobserver and interlaboratory scoring consistency. HER2 results were scored
      from 45 breast cancers in 7 laboratories using the Ventana (Tucson, AZ) INFORM
      HER-2 SISH assay and in 1 central laboratory using a standard FISH assay.
      Overall, 94.8% of cases were successfully analyzed by SISH across the 6
      participating laboratories that reported data. Concordance for diagnosis of HER2
      amplification by SISH compared with FISH was high (96.0% overall). Intraobserver
      variability (8.0%) and intersite variability (12.66%) of absolute HER2/chromosome
      17 ratios appear to be tightly controlled across all 6 participating
      laboratories. The Ventana INFORM HER-2 SISH assay is robust and reproducible,
      shows good concordance with a standard FISH assay, and complies with requirements
      in national guidelines for performance of diagnostic tests.

PMID- 19762529
TI  - Usefulness of a synoptic data tool for reporting of head and neck neoplasms based
      on the College of American Pathologists cancer checklists.
AB  - The primary source of information that clinicians use when evaluating and
      managing patients with cancer is the surgical pathology report. Omission of
      critical information from the report is a recognized problem in pathology,
      especially considering the expanding amount of information, such as molecular
      diagnostics data, that is now routinely included in reports. To standardize
      surgical pathology reports, the College of American Pathologists (CAP) introduced
      the CAP checklists. In 2004, the American College of Surgeons Commission on
      Cancer mandated that 90% of pathology reports indicating a cancer diagnosis at
      participating centers contain all scientifically validated or regularly used data
      elements. The University of Pittsburgh Medical Center has implemented synoptic
      reporting based on the CAP checklists for all major tumor types. We report our
      experience with synoptic reporting on head and neck neoplasms, demonstrating, in
      particular, how this can be customized according to needs of each institution.

PMID- 19762530
TI  - CDX-2 expression is a common event in primary intestinal-type endocervical
      adenocarcinoma.
AB  - We studied the expression of cytokeratin (CK) 7, CK20, CDX-2, and p16 in 119
      cervical adenocarcinomas (65 usual type [50 invasive; 15 in situ], 37 intestinal
      type [21 invasive; 16 in situ], 10 endometrioid, 5 adenosquamous, and 2 signet
      ring carcinomas) in comparison with 55 cases of rectal adenocarcinomas. The
      percentage of cells staining was considered negative if 0% to 5% stained; more
      than 5% was considered positive. For p16, staining of more than 50% was
      considered positive. CK7 was expressed in all cervical cases and in 12 rectal
      adenocarcinomas (22%). CK20 was expressed in 17 cervical adenocarcinomas (14.3%)
      and in 48 rectal adenocarcinomas (87%). CK20 immunostaining was diffuse in the
      majority of rectal tumors but focal in most cervical tumors. CDX-2 was expressed
      in all cases of rectal adenocarcinoma and in 46 cervical adenocarcinomas (38.7%):
      usual type, 10 (15%); intestinal type, 31 (84%); endometrioid type, 5 (50%);
      adenosquamous and signet-ring types, 0 (0%). CDX-2 is a marker for intestinal
      differentiation irrespective of a rectal or cervical origin. Therefore, it should
      not be used as the sole basis to confirm the colorectum as the primary origin in
      metastatic cases.

PMID- 19762531
TI  - Emerging technologies for assessing HER2 amplification.
AB  - Patients with human epidermal growth factor receptor-2 (HER2)+ breast cancer are
      eligible for trastuzumab treatment; therefore, accurate assessment of HER2 status
      is essential. Until recently, only 2 methods were validated for determining the
      HER2 status of breast tumors in the routine diagnostic setting:
      immunohistochemical analysis and fluorescence in situ hybridization (FISH).
      Recently, bright-field in situ hybridization techniques such as chromogenic in
      situ hybridization (CISH) and silver-enhanced in situ hybridization (SISH), which
      combine features of immunohistochemical analysis and FISH, have been introduced
      for the determination of HER2 status. These new techniques use a peroxidase
      enzyme-labeled probe with chromogenic detection, instead of a fluorescent-labeled
      probe, allowing results to be visualized by standard bright-field microscopy.
      Thus, the histologic features and HER2 status of a specimen can be evaluated in
      parallel. Moreover, signals do not decay over time. This review discusses recent
      publications regarding CISH and SISH testing, including results scoring and
      concordance between FISH and immunohistochemical analysis.

PMID- 19762532
TI  - Influence of credentials of clinical laboratory professionals on proficiency
      testing performance.
AB  - The influence of the training, experience, and credentials of testing personnel
      in the increasingly complex laboratory is a significant concern. A retrospective
      study compared the relationship of proficiency testing (PT) performance with the
      credentials of the testing personnel using logistic regression analyses.
      Predictor variables included the practitioner's college major, degree,
      certification, and years of laboratory experience. There were 14,326 valid PT
      results and 359 practitioners of whom 245 (68.2%) had a clinical laboratory
      science major. Logistic regression analysis revealed that participants without a
      clinical laboratory science major were more likely (adjusted odds ratio, 1.849; P
      = .035) to produce unacceptable results compared with participants whose academic
      history included a clinical laboratory science program. These data suggest that
      clinical laboratories should be staffed by people who have completed a formal
      clinical laboratory education program to ensure quality of laboratory testing and
      to reduce the risk of medical errors.

PMID- 19762533
TI  - Implementing and validating transcutaneous bilirubinometry for neonates.
AB  - Noninvasive, transcutaneous bilirubin (TcB) measurement is an attractive option
      for neonates, but opinions about its usefulness vary among studies. We collected
      paired measurements of TcB and serum bilirubin (SB) in 343 term neonates using
      the BiliCheck meter (SpectRx, Norcross, GA) and 3 different SB methods.
      Correlations between SB and TcB were similar for all laboratory methods and TcB
      measurement sites. However, TcB bias varied depending on the comparison SB method
      and TcB measurement site. TcB bias also varied with race when measurements were
      done on the forehead but not when they were done on the sternum. Several factors
      must be considered before implementing TcB measurement: (1) Each laboratory
      instrument has its own unique relationship to TcB. (2) The chosen measurement
      site affects the relationship. (3) Race can affect TcB bias when the measurement
      is taken on the forehead. Properly used, TcB measurement, especially when taken
      from the sternum, can be a useful screening method for neonatal jaundice.

PMID- 19762534
TI  - Use of a FLAER-based WBC assay in the primary screening of PNH clones.
AB  - Diagnosis of paroxysmal nocturnal hemoglobinuria (PNH) with flow cytometry
      traditionally involves the analysis of CD55 and CD59 on RBCs and neutrophils.
      However, the ability to accurately detect PNH RBCs is compromised by prior
      hemolysis and/or transfused RBCs. Patients with aplastic anemia (AA) and
      myelodysplastic syndrome (MDS) can also produce PNH clones. We recently described
      a multiparameter fluorescent aerolysin (FLAER)-based flow assay using CD45, CD33,
      and CD14 that accurately identified PNH monocyte and neutrophil clones in PNH,
      AA, and MDS. Here, we compared the efficiency of this WBC assay with a CD59-based
      assay on RBCs during a 3-year period. PNH clones were detected with the FLAER
      assay in 63 (11.8%) of 536 samples tested, whereas PNH RBCs were detected in only
      33 (6.2%), and always with a smaller clone size. The FLAER assay on WBCs is a
      more sensitive and robust primary screening assay for detecting PNH clones in
      clinical samples.

PMID- 19762535
TI  - Distinct expression patterns of CD123 and CD34 on normal bone marrow B-cell
      precursors ("hematogones") and B lymphoblastic leukemia blasts.
AB  - We compared the expression of CD123, the alpha chain of the interleukin-3
      receptor, on normal B-cell precursors in bone marrow ("hematogones") from 75
      specimens and on leukemic blasts in 45 newly diagnosed B-acute lymphoblastic
      leukemias (B-ALL) cases. We found that the less mature hematogones (dim CD45+)
      that express CD34 lack CD123 expression, whereas the more mature hematogones
      (moderate CD45+) lack CD34 but always express CD123. In contrast with this
      discordant pattern of CD34 and CD123 expression in hematogones, blasts in 41
      (91%) of 45 cases of B-ALL showed concordant expression of the 2 antigens: 80%
      (36 of 45) cases expressed both antigens, whereas 11% (5 of 45) expressed
      neither. We found that these distinct patterns of CD34/CD123 expression on
      hematogones (discordant) and B-ALL blasts (concordant) remain stable after
      chemotherapy and are useful in differentiating small populations of residual
      blasts from hematogones that may be simultaneously present.

PMID- 19762536
TI  - Extramedullary plasmacytoma-like posttransplantation lymphoproliferative
      disorders: clinical and pathologic features.
AB  - Most monomorphic posttransplantation lymphoproliferative disorders (PTLDs)
      resemble diffuse large B-cell lymphoma or Burkitt lymphoma. Rare cases of PTLD
      resembling extramedullary plasmacytomas have also been described. This report
      describes the clinical, histologic, phenotypic, and genotypic findings in 4 cases
      of plasmacytoma-like PTLD (2 nodal, 1 adenoidal, and 1 cutaneous) and compares
      the findings with extramedullary involvement by plasma cell neoplasms arising in
      immunocompetent patients. Plasmacytoma-like PTLDs characteristically arise late
      after transplantation (mean, 7.0 years), show a variable association with Epstein
      Barr virus (2/4 cases positive), and demonstrate histologic and phenotypic
      findings that overlap with immunocompetent extramedullary plasma cell neoplasms.
      None of the patients with plasmacytoma-like PTLD developed lytic bone lesions,
      and 3 of 4 patients had complete responses (>2 years) to reduction of
      immunosuppression, confirming the role of immunosuppression in the pathogenesis
      of these lesions. This report, which represents the first case series of
      plasmacytoma-like PTLD, clarifies the features of this rare subtype of PTLD.

PMID- 19762537
TI  - High expression of the inhibitory receptor BTLA in T-follicular helper cells and
      in B-cell small lymphocytic lymphoma/chronic lymphocytic leukemia.
AB  - B- and T-lymphocyte attenuator (BTLA) is a lymphoid receptor that inhibits
      lymphocyte activation on interaction with its ligand, herpesvirus entry mediator
      (HVEM). We developed monoclonal antibodies against BTLA and HVEM to study their
      expression using immunohistochemical and flow cytometric analyses in human
      tissues. In reactive lymph nodes, they were both expressed in interfollicular T
      cells and in B cells from mantle and marginal zones. Within germinal centers, B
      cells were negative, whereas T follicular helper (TFH) cells were BTLA+ and
      follicular dendritic cells were HVEM+. BTLA was strongly expressed in chronic
      lymphocytic leukemia/small lymphocytic lymphoma (B-CLL/SLL, 19 of 19 positive)
      when compared with other small B-cell lymphomas, including follicular lymphoma (0
      of 24 positive), mantle cell lymphoma (0 of 10 positive), and marginal zone
      lymphoma (0 of 5 positive). Our results suggest that down-regulation of the BTLA
      HVEM pathway may be involved in germinal center B-cell activation. The specific
      high expression of BTLA in B-CLL/SLL represents a new potential diagnostic tool.
      The BTLA positivity of TFH cells may be a basis for designing future
      immunotherapies.

PMID- 19762538
TI  - Plasmablastic lymphomas with MYC/IgH rearrangement: report of three cases and
      review of the literature.
AB  - We report detailed clinicopathologic features of 3 cases of plasmablastic
      lymphoma (PBL) with MYC/IgH rearrangement, representing one third of PBL cases
      diagnosed at our institution. This study brings the total number of reported
      cases in the literature to 6. All patients were HIV+ with very low CD4 counts at
      diagnosis. The involved locations were mediastinum, anus, and bone marrow. Tumors
      exhibited predominantly immunoblastic/plasmablastic morphologic features and had
      a plasma cell-like immunophenotype. Bright CD38 expression by flow cytometry had
      a tendency to be more common in these cases compared with PBL without MYC
      rearrangement. All cases were positive for Epstein-Barr virus-encoded RNA but
      lacked human herpesvirus-8 latent nuclear antigen. The 2 patients with follow-up
      died within 3 months. These findings show that PBL is often associated with
      MYC/IgH rearrangements and that this finding may portend an aggressive clinical
      course, suggesting that cytogenetic studies should be routinely applied in cases
      of PBL.

PMID- 19762539
TI  - Automated assay for fondaparinux (Arixtra) on the Dade Behring BCS XP.
AB  - An assay for fondaparinux (Arixtra) is described based on a modified commercial
      assay for heparin. The assay is automated on a Dade Behring BCS XP (Siemens
      Healthcare Diagnostics, Deerfield, IL) and uses the inhibition of activated
      factor X to quantitate the drug. The assay was unaffected by platelet
      contamination or the presence of warfarin. The assay was affected by the
      antithrombin level, and the value obtained in the assay decreased significantly
      when the antithrombin level was less than 60%. The assay is, however, not
      specific for fondaparinux. Specimens containing unfractionated or low-molecular
      weight heparin will yield results by this assay that will not be an accurate
      estimation of concentration.

PMID- 19762540
TI  - Newer antiphospholipid antibodies predict adverse outcomes in patients with acute
      coronary syndrome.
AB  - Antiphospholipid antibodies (aPLs) have been implicated in atherogenesis. We
      studied 344 patients with acute coronary syndromes; approximately 40% were aPL+
      in 1 or more tests and 60% aPL-. In 215 patients, coronary artery disease (CAD)
      was angiographically documented, with 43.7% positive for aPL vs 34.9% of patients
      without CAD positive for aPLs. Anti-beta(2)-glycoprotein I (beta2GPI; 54%) and
      anti-oxidized low-density lipoprotein (oxLDL)/beta2GPI (48%) were most frequent,
      accounting for 87% of all aPL+ CAD cases. aPLs correlated with severity of CAD (P
      = .012). Adverse events occurred in 16.7% of patients with CAD, more frequently
      in patients who were aPL+ (P = .0006; relative risk, 2.9; 95% confidence
      interval, 1.5-5.6). Patients who were aPL+ with severe CAD had more adverse
      events than patients who were aPL- with severe CAD (P = .005) and aPL+ patients
      undergoing revascularization procedures (P = .001). Vascular events occurred in
      21.7% of aPL+ patients compared with 7.1% of aPL- patients (P = .005). Anti
      beta2GPI and anti-oxLDL/beta2GPI were associated with CAD severity and adverse
      outcomes.

PMID- 19762541
TI  - Separating thalassemia trait and iron deficiency by even simpler inspection.

PMID- 19762543
TI  - Minireview: Nuclear receptor-controlled steroid hormone synthesis and metabolism.
AB  - Steroid hormones are essential in normal physiology whereas disruptions in
      hormonal homeostasis represent an important etiological factor for many human
      diseases. Steroid hormones exert most of their functions through the binding and
      activation of nuclear hormone receptors (NRs or NHRs), a superfamily of DNA
      binding and often ligand-dependent transcription factors. In recent years,
      accumulating evidence has suggested that NRs can also regulate the biosynthesis
      and metabolism of steroid hormones. This review will focus on the recent progress
      in our understanding of the regulatory role of NRs in hormonal homeostasis and
      the implications of this regulation in physiology and diseases.

PMID- 19762544
TI  - Androgen-responsive gene database: integrated knowledge on androgen-responsive
      genes.
AB  - Androgen signaling plays an important role in many biological processes. Androgen
      Responsive Gene Database (ARGDB) is devoted to providing integrated knowledge on
      androgen-controlled genes. Gene records were collected on the basis of PubMed
      literature collections. More than 6000 abstracts and 950 original publications
      were manually screened, leading to 1785 human genes, 993 mouse genes, and 583 rat
      genes finally included in the database. All the collected genes were
      experimentally proved to be regulated by androgen at the expression level or to
      contain androgen-responsive regions. For each gene important details of the
      androgen regulation experiments were collected from references, such as
      expression change, androgen-responsive sequence, response time, tissue/cell type,
      experimental method, ligand identity, and androgen amount, which will facilitate
      further evaluation by researchers. Furthermore, the database was integrated with
      multiple annotation resources, including National Center for Biotechnology
      Information, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathway,
      to reveal the biological characteristics and significance of androgen-regulated
      genes. The ARGDB web site is mainly composed of the Browse, Search, Element Scan,
      and Submission modules. It is user friendly and freely accessible at
      http://argdb.fudan.edu.cn. Preliminary analysis of the collected data was
      performed. Many disease pathways, such as prostate carcinogenesis, were found to
      be enriched in androgen-regulated genes. The discovered androgen-response motifs
      were similar to those in previous reports. The analysis results are displayed in
      the web site. In conclusion, ARGDB provides a unified gateway to storage,
      retrieval, and update of information on androgen-regulated genes.

PMID- 19762545
TI  - Functional screening of FxxLF-like peptide motifs identifies SMARCD1/BAF60a as an
      androgen receptor cofactor that modulates TMPRSS2 expression.
AB  - Androgen receptor (AR) transcriptional activity is tightly regulated by
      interacting cofactors and cofactor complexes. The best described cofactor
      interaction site in the AR is the hormone-induced coactivator binding groove in
      the ligand-binding domain, which serves as a high-affinity docking site for FxxLF
      like motifs. This study aimed at identifying novel AR cofactors by in silico
      selection and functional screening of FxxLF-like peptide motifs. Candidate
      interacting motifs were selected from a proteome-wide screening and from a
      supervised screening focusing on components of protein complexes involved in
      transcriptional regulation. Of the 104 peptides tested, 12 displayed moderate to
      strong in vivo hormone-dependent interactions with AR. For three of these,
      ZBTB16/PLZF, SMARCA4/BRG1, and SMARCD1/BAF60a, the full-length protein was tested
      for interaction with AR. Of these, BAF60a, a subunit of the SWI/SNF chromatin
      remodeling complex, displayed hormone-dependent interactions with AR through its
      FxxFF motif. Vice versa, recruitment of BAF60a by the AR required an intact
      coactivator groove. BAF60a depletion by small interfering RNA in LNCaP cells
      demonstrated differential effects on expression of endogenous AR target genes. AR
      driven expression of TMPRSS2 was almost completely blocked by BAF60a small
      interfering RNA. In summary, our data demonstrate that BAF60a directly interacts
      with the coactivator groove in the AR ligand-binding domain via its FxxFF motif,
      thereby selectively activating specific AR-driven promoters.

PMID- 19762546
TI  - 20-125Iodo-14,15-epoxyeicosa-5(Z)-enoic acid: a high-affinity radioligand used to
      characterize the epoxyeicosatrienoic acid antagonist binding site.
AB  - Epoxyeicosatrienoic acids (EETs) are endothelium-derived metabolites of
      arachidonic acid. They relax vascular smooth muscle by membrane
      hyperpolarization. These actions are inhibited by the EET antagonist, 14,15
      epoxyeicosa-5(Z)-enoic acid (14,15-EE5ZE). We synthesized 20-(125)iodo-14,15
      EE5ZE (20-(125)I-14,15-EE5ZE), a radiolabeled EET antagonist, and characterized
      its binding to cell membranes. 14,15-EET (10(-9)-10(-5)M) caused a concentration
      related relaxation of the preconstricted bovine coronary artery and
      phosphorylation of p38 in U937 cells that were inhibited by 20-(125)I-14,15
      EE5ZE. Specific 20-(125)I-14,15-EE5ZE binding to U937 cell membranes reached
      equilibrium within 5 min and remained unchanged for 30 min. The binding was
      saturable and reversible, and it exhibited K(D) and B(max) values of 1.11 +/-
      0.13 nM and 1.13 +/- 0.04 pmol/mg protein, respectively. Guanosine 5'-O-(3
      thio)triphosphate (10 muM) did not change the binding, indicating antagonist
      binding of the ligand. Various EETs and EET analogs (10(-10)-10(-5)M) competed
      for 20-(125)I-14,15-EE5ZE binding with an order of potency of 11,12-EET = 14,15
      EET > 8,9-EET = 14,15-EE5ZE > 15-hydroxyeicosatetraenoic acid = 14,15
      dihydroxyeicosatrienoic acid. 8,9-Dihydroxyeicosatrienoic acid and 11
      hydroxyeicosatetraenoic acid did not compete for binding. The soluble and
      microsomal epoxide hydrolase inhibitors (1-cyclohexyl-3-dodecyl-urea, elaidamide,
      and 12-hydroxyl-elaidamide) and cytochrome P450 inhibitors (sulfaphenazole and
      proadifen) did not compete for the binding. However, two cytochrome P450
      inhibitors, N-methylsulfonyl-6-(2-propargyloxyphenyl)hexanamide (MS-PPOH) and
      miconazole competed for binding with K(i) of 1558 and 315 nM, respectively.
      Miconazole and MS-PPOH, but not proadifen, inhibited 14,15-EET-induced
      relaxations. These findings define an EET antagonist's binding site and support
      the presence of an EET receptor. The inhibition of binding by some cytochrome
      P450 inhibitors suggests an alternative mechanism of action for these drugs and
      could lead to new drug candidates that target the EET binding sites.

PMID- 19762547
TI  - Mesalamine restores angiogenic balance in experimental ulcerative colitis by
      reducing expression of endostatin and angiostatin: novel molecular mechanism for
      therapeutic action of mesalamine.
AB  - Mesalamine (5-aminosalicylate acid, 5-ASA) is an effective treatment for
      ulcerative colitis (UC). The mechanisms of its actions are not fully understood.
      Because angiogenesis is critical for healing UC, we examined whether 5-ASA alters
      the angiogenic balance between angiogenic factors [e.g., vascular endothelial
      growth factor (VEGF)] and antiangiogenic factors (e.g., endostatin and
      angiostatin) in the colon in experimental UC. Rats were treated with saline or 5
      ASA (100 mg/kg) twice daily and euthanized 3 or 7 days after iodoacetamide
      induced UC. Clinical signs (e.g., lethargy, diarrhea) and UC lesions were
      measured. Expression of VEGF, endostatin, angiostatin, tissue necrosis factor
      alpha (TNF-alpha), and matrix metalloproteinases (MMPs) 2 and 9 was determined by
      Western blots, enzyme-linked immunosorbent assay, and zymography in the distal
      colon. 5-ASA treatment reduced lethargy and diarrhea and significantly decreased
      colonic lesions (by approximately 50%) compared with saline treatment in UC
      (both, P < 0.05). 5-ASA did not reverse the increased levels of VEGF, but it
      significantly reduced expression of endostatin and angiostatin in UC compared
      with vehicle treatment (both, P < 0.05). Furthermore, 5-ASA treatment
      significantly diminished increased activity of TNF-alpha and MMP9 in UC. This is
      the first demonstration that 5-ASA treatment reverses an imbalance between the
      angiogenic factor VEGF and antiangiogenic factors endostatin and angiostatin in
      experimental UC. The effect of 5-ASA in UC may be caused by the down-regulation
      of expression of endostatin and angiostatin by modulation of MMP2 and MMP9 via
      inhibition of TNFalpha. The inhibition of antiangiogenic factors may represent a
      novel molecular mechanism of the therapeutic action of 5-ASA.

PMID- 19762548
TI  - Automated high-content screening for compounds that disassemble the perinucleolar
      compartment.
AB  - All solid malignancies share characteristic traits, including unlimited cellular
      proliferation, evasion of immune regulation, and the propensity to metastasize.
      The authors have previously described that a subnuclear structure, the
      perinucleolar compartment (PNC), is associated with the metastatic phenotype in
      solid tumor cancer cells. The percentage of cancer cells that contain PNCs (PNC
      prevalence) is indicative of the malignancy of a tumor both in vitro and in vivo,
      and thus PNC prevalence is a marker that reflects metastatic capability in a
      population of tumor cells. Although the function of the PNC remains to be
      determined, the PNC is highly enriched with small RNAs and RNA binding proteins.
      The initial chemical biology studies using a set of anticancer drugs that
      disassemble PNCs revealed a direct association of the structure with DNA.
      Therefore, PNC prevalence reduction as a phenotypic marker can be used to
      identify compounds that target cellular processes required for PNC maintenance
      and hence used to elucidate the nature of the PNC function. Here the authors
      report the development of an automated high-content screening assay that is
      capable of detecting PNC prevalence in prostate cancer cells (PC-3M) stably
      expressing a green fluorescent protein (GFP)-fusion protein that localizes to the
      PNC. The assay was optimized using known PNC-reducing drugs and non-PNC-reducing
      cytotoxic drugs. After optimization, the fidelity of the assay was probed with a
      collection of 8284 compounds and was shown to be robust and capable of detecting
      known and novel PNC-reducing compounds, making it the first reported high-content
      phenotypic screen for small changes in nuclear structure.

PMID- 19762549
TI  - Predictors of symptoms of posttraumatic stress and depression in family members
      after patient death in the ICU.
AB  - BACKGROUND: Patients' deaths in the ICU have been associated with a high burden
      of psychologic symptoms in families. This study identifies characteristics
      associated with psychologic symptoms in family members. METHODS: Families of
      patients dying in the ICU or within 30 h of ICU discharge in 11 hospitals
      previously participated in a randomized trial. In the current study, we assessed
      these families for symptoms of posttraumatic stress disorder (PTSD) and
      depression with follow-up surveys. Outcomes included validated measures of PTSD
      (PTSD Checklist) and depressive (Patient Health Questionnaire) symptoms.
      Predictors included family member mental-health history, involvement in decision
      making, and demographics. RESULTS: Surveys were completed by 226 families.
      Response rate was 46% in the original randomized trial and 82% in this study.
      Prevalence (95% CI) of PTSD and depressive symptoms were 14.0% (9.7%-19.3%) and
      18.4% (13.5%-24.1%), respectively. Family characteristics associated with
      increased symptoms included: female gender (PTSD, P = .020; depression, P =
      .005), knowing the patient for a shorter duration (PTSD, P = .003; depression, P
      = .040), and discordance between family members' preferences for decision making
      and their actual decision-making roles (PTSD, P = .005; depression, P = .049).
      Depressive symptoms were also associated with lower educational level (P = .002).
      Families with psychologic symptoms were more likely to report that access to a
      counselor (PTSD, P < .001; depression, P = .003) and information about spiritual
      services might have been helpful while the patient was in the ICU (PTSD, P =
      .024; depression, P = .029). CONCLUSIONS: Families demonstrated a high prevalence
      of psychologic symptoms after a death in the ICU. Characteristics associated with
      symptoms may help target interventions to reduce these symptoms. TRIAL
      REGISTRATION: clinicaltrials.gov; Identifier: NCT00685893.

PMID- 19762550
TI  - Refining clinical risk stratification for predicting stroke and thromboembolism
      in atrial fibrillation using a novel risk factor-based approach: the euro heart
      survey on atrial fibrillation.
AB  - BACKGROUND: Contemporary clinical risk stratification schemata for predicting
      stroke and thromboembolism (TE) in patients with atrial fibrillation (AF) are
      largely derived from risk factors identified from trial cohorts. Thus, many
      potential risk factors have not been included. METHODS: We refined the 2006
      Birmingham/National Institute for Health and Clinical Excellence (NICE) stroke
      risk stratification schema into a risk factor-based approach by reclassifying
      and/or incorporating additional new risk factors where relevant. This schema was
      then compared with existing stroke risk stratification schema in a real-world
      cohort of patients with AF (n = 1,084) from the Euro Heart Survey for AF.
      RESULTS: Risk categorization differed widely between the different schemes
      compared. Patients classified as high risk ranged from 10.2% with the Framingham
      schema to 75.7% with the Birmingham 2009 schema. The classic CHADS(2) (Congestive
      heart failure, Hypertension, Age > 75, Diabetes, prior Stroke/transient ischemic
      attack) schema categorized the largest proportion (61.9%) into the intermediate
      risk strata, whereas the Birmingham 2009 schema classified 15.1% into this
      category. The Birmingham 2009 schema classified only 9.2% as low risk, whereas
      the Framingham scheme categorized 48.3% as low risk. Calculated C-statistics
      suggested modest predictive value of all schema for TE. The Birmingham 2009
      schema fared marginally better (C-statistic, 0.606) than CHADS(2). However, those
      classified as low risk by the Birmingham 2009 and NICE schema were truly low risk
      with no TE events recorded, whereas TE events occurred in 1.4% of low-risk
      CHADS(2) subjects. When expressed as a scoring system, the Birmingham 2009 schema
      (CHA(2)DS(2)-VASc acronym) showed an increase in TE rate with increasing scores
      (P value for trend = .003). CONCLUSIONS: Our novel, simple stroke risk
      stratification schema, based on a risk factor approach, provides some improvement
      in predictive value for TE over the CHADS(2) schema, with low event rates in low
      risk subjects and the classification of only a small proportion of subjects into
      the intermediate-risk category. This schema could improve our approach to stroke
      risk stratification in patients with AF.

PMID- 19762551
TI  - Interactions of airflow oscillation, tracheal inclination, and mucus elasticity
      significantly improve simulated cough clearance.
AB  - BACKGROUND: Viscoelastic properties of simulated mucus, angle of tracheal
      inclination (theta), and high-frequency airflow oscillations on median
      displacement of simulated mucus during simulated cough were investigated in this
      study. METHODS: Mucus simulants with viscoelastic properties similar to healthy
      individuals and patients with COPD were prepared using locust bean gum (LBG)
      water solution (0.38 g LBG in 100 mL water) cross-linked with 3-mL and 12-mL
      borax-water solution (0.02 M), respectively. Aliquots of 0.3 mL of simulants were
      placed on a dry Plexiglas insert inside a D-shaped clear Plexiglas tracheal
      model. Movement of aliquots of mucus simulants was measured during cough of 0.3 s
      duration. Cough velocities studied (5-30 m/s) are typical of patients with weak
      expiratory muscles and airway obstruction. Studies were conducted with tracheal
      model placed horizontally (0 degrees) and at increasing theta (15 degrees, 30
      degrees, and 45 degrees), with and without superimposed airflow oscillations
      during coughs. Effects of different parameters and their interactions on
      displacements of aliquots were compared using analysis of covariance (n = 849).
      RESULTS: Significant positive nonlinear associations existed between displacement
      and cough velocity for both 3-mL and 12-mL simulants (P < .0001). Displacement
      was greatest for the cohesive 12-mL simulant at all cough velocities.
      Displacement increased significantly (P < .0001) as theta was increased for both
      types of simulants. Largest displacements at low cough velocities occurred with
      12-mL simulant in the presence of oscillations at 45 degrees angle. CONCLUSIONS:
      Results support the use of airflow oscillations and sitting upright to facilitate
      mucus displacement during cough, particularly with thick, elastic mucus found in
      patients with COPD (P < .0001).

PMID- 19762553
TI  - Improving diabetes care using a multitiered quality improvement model.
AB  - The authors report the results of implementing a diabetes mellitus guideline in a
      group practice in which uniform, technology-generated care processes were
      produced for patients, clinical staff, and providers. The objective was to
      increase the annual rate of recommended tests and examinations for patients with
      diabetes and to reduce levels of glycosylated hemoglobin, blood pressure, and low
      density lipoprotein cholesterol. A process change for type 2 diabetes mellitus
      was implemented that included changes in office visit structure, protocol-driven
      electronic prompts for nursing and physician staffs, clinical decision support
      built into a new electronic medical record form, and audit with feedback. Twelve
      primary care physicians treated a total of 1592 patients with diabetes between
      January 2007 and January 2008. There were prompt and statistically significant
      improvements in 5 process measures and 2 outcome measures; a quality summary
      measure showed 8% overall improvement. Statistically significant improvements
      with moderate effect size were observed after a multitiered intervention.

PMID- 19762552
TI  - Patient-specific, time-varying predictors of post-ICU informal caregiver burden:
      the caregiver outcomes after ICU discharge project.
AB  - BACKGROUND: The outcomes of informal caregivers of survivors of critical illness
      likely depend on patient characteristics, which may change over time. To date,
      few studies have examined patient-specific predictors of post-ICU informal
      caregiver burden, and none has tested whether predictors vary after hospital
      discharge. METHODS: We designed a prospective, longitudinal observational study,
      enrolling 48 patient-caregiver dyads from four ICUs in a university hospital.
      Informal caregiver depression symptoms were measured with the Center for
      Epidemiologic Studies Depression scale. Lifestyle disruption was measured with
      the Activity Restriction Scale. Linear regression models were built to test for
      patient- and caregiver-specific predictors of depression symptoms and lifestyle
      disruption 2, 6, and 12 months after ICU admission. RESULTS: Patients had a mean
      (SD) age of 52.5 (19.7) years, 67% were men, median (interquartile range) Acute
      Physiology and Chronic Health Evaluation score was 52 (38.5, 65). The caregivers
      had a mean (SD) age of 52.8 (12.8) years, 91.2% were women, and 48% were spouses.
      Predictors of caregiver depression symptoms were patient gender (men) at 2 and 12
      months and tracheostomy at 12 months. Predictors of lifestyle disruption were
      patient education (more common among high school graduates) and patient gender
      (men) at 2 months, and tracheostomy, functional dependency, and patient gender
      (men) at 12 months. CONCLUSIONS: The determinants of post-ICU informal caregiver
      burden likely depend on characteristics of the patient as well as the caregiver
      and may vary over time. Further research is necessary to better understand the
      longitudinal determinants of burden in order to develop more effective caregiver
      interventions.

PMID- 19762554
TI  - Life-course typology of adults who experienced sexual violence.
AB  - Two qualitative methodologies were used to develop a life-course typology of
      individuals who had been exposed to sexual violence. Interview narratives of 121
      adult women and men who participated in qualitative study of women's and men's
      responses to sexual violence provided the data. The authors combined a narrative
      approach (holistic-content and holistic-form analysis) to describe the life
      courses of the participants and a qualitative person-oriented approach (cross
      case analysis) to identify meaningful subgroups within the total sample. The six
      groups are as follows: (a) life of turmoil, (b) life of struggles, (c) diminished
      life, (d) taking control of life, (e), finding peace in life, and (f) getting
      life back to normal. This work exemplifies a promising strategy for identifying
      subgroups of violence-exposed individuals within a heterogeneous sample. Such a
      typology could aid the development of treatment approaches that consider both the
      substance and the structure of an individual's life course, rather than target
      one specific type of violence.

PMID- 19762555
TI  - IL-21 and IL-10 have redundant roles but differential capacities at different
      stages of Plasma Cell generation from human Germinal Center B cells.
AB  - The GC is the anatomical site where antigen-activated B cells differentiate into
      PC, producing high-affinity antibodies in physiological and pathological states.
      PC differentiation is regulated by multiple factors within the GC
      microenvironment, including cytokines. IL-21, a recently identified type I
      cytokine produced by GC-Th cells, promotes differentiation of human B cells into
      ISC. In this study, we investigated in detail the functional role of IL-21 in the
      course of GC-B cell differentiation into terminally differentiated PC compared
      with that of IL-10, a well-known PC differentiation factor. IL-21 had a greater
      capacity to initiate PC differentiation from CD77(+) centroblasts than IL-10 by
      strongly inducing PC transcription factors through activation of STAT3; however,
      IL-10 was more potent than IL-21 in generating CD138(+) PC from CD20(-)CD38(++)
      plasmablasts in the terminal stage of GC-B cell differentiation. This
      differential effect of IL-21 and IL-10 was reflected in receptor expression on B
      cell subsets emerging in the course of differentiation. Our studies have revealed
      that IL-21 is a critical decision-maker for driving initial PC differentiation at
      the stage of CD77(+) centroblasts, yet IL-10 is more effective in producing IgG
      by generating terminally differentiated CD138(+) PC at the later stage of PC
      differentiation in the GC.

PMID- 19762556
TI  - Generic binding sites, generic DNA-binding domains: where does specific promoter
      recognition come from?
AB  - A transcription reaction relies on the specific recognition of cis-regulatory
      regions containing short DNA motifs. Such sequences are bound by transcription
      factors (TFs) involved in the recruitment, direct or not, of the transcriptional
      machinery. A eukaryotic genome can contain tens of genes encoding TFs that
      recognize very similar consensus DNA target sequences. In this review, we explore
      in a simple way how TFs coexpressed in the same cells and recognizing generic
      consensus sites with generic DNA-binding domains can achieve a specific
      modulation of target gene expression. We dissect the strategy followed by
      eukaryotes, which involves the formation of complex nucleoprotein structures
      involving many TFs and their cognate binding sites. This multiplicity of actors
      increases the effective length of the target DNA recognized by the TFs and might
      help paralogous TFs establish specific interactions. From this perspective,
      eukaryotic gene regulation implies the cooperation of several TFs, which is also
      the basis of information integration. Such cooperative TFs are likely to form a
      combinatorial partner code whose ultimate molecular hallmark is the assembly of
      enhanceosome-like structures ensuring the formation of an activation surface that
      is complementary to other coactivators and to the transcriptional machinery
      itself.

PMID- 19762557
TI  - Chromatin remodeling: recruitment of histone demethylase RBP2 by Mad1 for
      transcriptional repression of a Myc target gene, telomerase reverse
      transcriptase.
AB  - The Myc/Max/Mad network transcription factors are known to govern target gene
      expression through recruiting histone acetyltransferases or deacetylases. In the
      present study, we show that Mad1 recruits the histone demethylase RBP2 to the Myc
      target telomerase reverse transcriptase (hTERT) gene promoter to repress
      transcription. With differentiation of leukemic HL60 cells, Mad1 and RBP2 were
      both up-regulated, interacted, and cooccupied the hTERT promoter accompanied by
      histone H3-K4 demethylation. In immortalized p493-6 B cells, shutting down c-Myc
      led to the accumulation of Mad1 and RBP2 at hTERT promoter and diminished hTERT
      mRNA expression. When RBP2 was depleted, hTERT expression was significantly
      enhanced, coupled with dissociation of RBP2 with and increased H3-K4 methylation
      at the hTERT promoter in p493-6 cells. Moreover, RBP2 and Mad1 were present on
      the hTERT promoter in human fibroblasts having a silent hTERT gene, and RBP2
      depletion resulted in gene derepression. Taken together, Mad1 recruits RBP2 to
      the hTERT promoter that, in turn, demethylates H3-K4, thereby contributing to a
      stable repression of the hTERT gene in normal or differentiated malignant cells.
      Our findings reveal a novel mechanism through which the Myc/Max/Mad network
      proteins control their target gene transcription and provide insights into
      mechanisms underlying telomerase silencing and activation.

PMID- 19762558
TI  - Cell fusion of bone marrow cells and somatic cell reprogramming by embryonic stem
      cells.
AB  - Bone marrow transplantation is a curative treatment for many diseases, including
      leukemia, autoimmune diseases, and a number of immunodeficiencies. Recently, it
      was claimed that bone marrow cells transdifferentiate, a much desired property as
      bone marrow cells are abundant and therefore could be used in regenerative
      medicine to treat incurable chronic diseases. Using a Cre/loxP system, we studied
      cell fusion after bone marrow transplantation. Fused cells were chiefly Gr-1(+),
      a myeloid cell marker, and found predominantly in the bone marrow; in parenchymal
      tissues. Surprisingly, fused cells were most abundant in the kidney, Peyer's
      patches, and cardiac tissue. In contrast, after cell fusion with embryonic stem
      cells, bone marrow cells were reprogrammed into new tetraploid pluripotent stem
      cells that successfully differentiated into beating cardiomyocytes. Together,
      these data suggest that cell fusion is ubiquitous after cellular transplants and
      that the subsequent sharing of genetic material between the fusion partners
      affects cellular survival and function. Fusion between tumor cells and bone
      marrow cells could have consequences for tumor malignancy.

PMID- 19762559
TI  - Caenorhabditis elegans P5B-type ATPase CATP-5 operates in polyamine transport and
      is crucial for norspermidine-mediated suppression of RNA interference.
AB  - Physiological polyamines are required in various biological processes. In the
      current study, we used norspermidine, a structural analog of the natural
      polyamine spermidine, to investigate polyamine uptake in the model organism
      Caenorhabditis elegans. Norspermidine was found to have two remarkable effects:
      it is toxic for the nematode, without affecting its food, Escherichia coli; and
      it hampers RNA interference. By characterizing a norspermidine-resistant C.
      elegans mutant strain that has been isolated in a genetic screen, we demonstrate
      that both effects, as well as the uptake of a fluorescent polyamine-conjugate,
      depend on the transporter protein CATP-5, a novel P(5B)-type ATPase. To our
      knowledge, CATP-5 represents the first P(5)-type ATPase that is associated with
      the plasma membrane, being expressed in the apical membrane of intestinal cells
      and the excretory cell. Moreover, genetic interaction studies using C. elegans
      polyamine synthesis mutants indicate that CATP-5 has a function redundant to
      polyamine synthesis and link reduced polyamine levels to retarded postembryonic
      development, reduced brood size, shortened life span, and small body size. We
      suggest that CATP-5 represents a crucial component of the pharmacologically
      important polyamine transport system, the molecular nature of which has not been
      identified so far in metazoa.

PMID- 19762560
TI  - Interaction with synphilin-1 promotes inclusion formation of alpha-synuclein:
      mechanistic insights and pathological implication.
AB  - alpha-Synuclein (alpha-Syn) is the major component of Lewy bodies (LBs) deposited
      in the brains of patients with Parkinson's disease. Synphilin-1 (Sph1) is a novel
      alpha-Syn-interacting protein also present in the LBs. However, the roles of
      alpha-Syn-Sph1 interaction in LB formation and in the related pathogenesis are
      still unclear. We have studied the interaction between alpha-Syn and Sph1 by
      biochemical and structural approaches and found that the central coiled-coil
      domain of Sph1 specifically interacts with the N-terminal stretch of alpha-Syn.
      When overexpressed in HEK 293T cells, Sph1 forms inclusions together with alpha
      Syn, but the Sph1-positive inclusions cannot recruit the N-terminally truncated
      alpha-Syn. The central portion of Sph1 can also recruit alpha-Syn and induce
      inclusion formation through its coiled-coil domain. These observations
      demonstrate that the alpha-Syn-Sph1 interaction significantly promotes the
      formation of cytoplasmic alpha-Syn inclusions, which may have implications for LB
      formation in neural cells. We have also elucidated solution structure of the
      coiled-coil domain of Sph1 and its interaction with the N-terminal peptide of
      alpha-Syn. The specific interaction between alpha-Syn and Sph1 provides
      mechanistic insights into the inclusion-body formation in cells and pathological
      implication in Parkinson's disease.

PMID- 19762561
TI  - Vascular endothelial growth factor drives autocrine epithelial cell proliferation
      and survival in chronic rhinosinusitis with nasal polyposis.
AB  - RATIONALE: The pathogenesis of nasal polyps in chronic rhinosinusitis is poorly
      understood. OBJECTIVES: These studies seek to implicate a functional role for
      vascular endothelial growth factor (VEGF) in perpetuating primary nasal
      epithelial cell overgrowth, a key feature of hyperplastic polyps. METHODS:
      Comparison of VEGF and receptor expression was assessed by ELISA of nasal lavage,
      immunohistochemistry of sinus tissue, flow cytometry of nasal epithelial cells,
      and ELISA of supernatants. VEGF-dependent cell growth and apoptosis were assessed
      with blocking antibodies to VEGF, their receptors, or small interfering RNA
      knockdown of neuropilin-1 by cell proliferation assays and flow cytometric
      binding of annexin V. MEASUREMENTS AND MAIN RESULTS: VEGF protein was sevenfold
      higher in nasal lavage from patients with polyposis compared with control
      subjects (P < 0.001). We also report elevated expression of VEGF (P < 0.012),
      receptors VEGFR2 and phospho-VEGFR2 (both P < 0.04), and identification of VEGF
      coreceptor neuropilin-1 in these tissues. Nasal epithelial cells from patients
      with polyps demonstrated faster growth rates (P < 0.005). Exposure of cells to
      blocking antibodies against VEGF resulted in inhibition of cell growth (P <
      0.05). VEGF receptor blockade required blockade of neuropilin-1 (P < 0.05) and
      resulted in increased apoptosis (P < 0.001) and inhibition of autocrine
      epithelial VEGF production (P < 0.05). CONCLUSIONS: These data demonstrate that
      VEGF is a novel biomarker for chronic rhinosinusitis with hyperplastic sinonasal
      polyposis that functions in an autocrine feed-forward manner to promote nasal
      epithelial cell growth and to inhibit apoptosis. These findings implicate a
      previously unrecognized and novel role of VEGF functioning through neuropilin-1
      on nonneoplastic primary human airway epithelial cells, to amplify cell growth,
      contributing to exuberant hyperplastic polyposis.

PMID- 19762562
TI  - Bbeta(15-42) protects against acid-induced acute lung injury and secondary
      pseudomonas pneumonia in vivo.
AB  - RATIONALE: Acute lung injury (ALI) is a serious condition in critically ill
      patients that predisposes to secondary bacterial pneumonia. Vascular leak is a
      hallmark in the pathogenesis of ALI. The fibrin-derived peptide Bbeta(15-42) was
      shown to preserve endothelial barriers, thereby reducing vascular leak. The
      potential therapeutic role of Bbeta(15-42) in ALI has not been addressed so far.
      OBJECTIVES: To investigate the therapeutic potential of Bbeta(15-42) in ALI and
      secondary pneumonia induced by Pseudomonas aeruginosa. METHODS: The effect of the
      fibrin-derived peptide Bbeta(15-42) was studied in models of ALI, induced either
      by pulmonary administration of LPS or hydrochloric acid. Lung inflammation was
      analyzed by quantifying cell influx, cytokine levels, and oxidized lipids.
      Vascular leak was determined by Evans Blue extravasations and alveolar protein
      content. In subsequent two-hit studies, mice were infected with P. aeruginosa 24
      hours after induction of aspiration pneumonitis and effects of Bbeta(15-42) on
      inflammation, bacterial clearance, and survival were evaluated. MEASUREMENTS AND
      MAIN RESULTS: After LPS or acid inhalation, proinflammatory cytokine levels,
      neutrophil influx, and vascular leak were found diminished in mice treated with
      Bbeta(15-42). Acid aspiration impaired macrophage functions and rendered mice
      more susceptible to subsequent P. aeruginosa infection, whereas mice that
      received Bbeta(15-42) during acid aspiration and were subsequently challenged
      with bacteria displayed reduced inflammation, enhanced bacterial clearance, and
      ultimately improved survival. CONCLUSIONS: The fibrin-derived peptide Bbeta(15
      42) exerted protective effects during ALI, resulting in diminished lung injury
      and preserved antibacterial properties of macrophages, which improved outcome
      during subsequent P. aeruginosa pneumonia.

PMID- 19762563
TI  - Anti-proline-glycine-proline or antielastin autoantibodies are not evident in
      chronic inflammatory lung disease.
AB  - RATIONALE: In patients with chronic inflammatory lung disease, pulmonary
      proteases can generate neoantigens from elastin and collagen with the potential
      to fuel autoreactive immune responses. Antielastin peptide antibodies have been
      implicated in the pathogenesis of tobacco-smoke-induced emphysema. Collagen
      derived peptides may also play a role. OBJECTIVES: To determine whether
      autoantibodies directed against elastin- and collagen-derived peptides are
      present in plasma from three groups of patients with chronic inflammatory lung
      disease compared with a nonsmoking healthy control group and to identify whether
      autoimmune responses to these peptides may be an important component of the
      disease process in these patients. METHODS: A total of 124 patients or healthy
      control subjects were recruited for the study (Z-A1AT deficiency, n = 20; cystic
      fibrosis, n = 40; chronic obstructive pulmonary disease, n = 31; healthy control,
      n = 33). C-reactive protein, IL-32, and antinuclear antibodies were quantified.
      Antielastin and anti-N-acetylated-proline-glycine-proline autoantibodies were
      measured by reverse ELISA. MEASUREMENTS AND MAIN RESULTS: All patients were
      deemed stable and noninfective on the basis of the absence of clinical or
      radiographic evidence of recent infection. There were no significant differences
      in the levels of autoantibodies or IL-32 in the patients groups compared with the
      healthy control subjects. CONCLUSIONS: Antielastin or anti-N-acetylated proline
      glycine-proline autoantibodies are not evident in chronic inflammatory lung
      disease.

PMID- 19762564
TI  - Maternal exposure to particulate matter increases postnatal ozone-induced airway
      hyperreactivity in juvenile mice.
AB  - RATIONALE: Epidemiologic studies implicate air pollutant exposure during
      pregnancy as a risk factor for wheezing in offspring. Ozone exposure is linked to
      exacerbations of wheezing in children. OBJECTIVES: To determine if maternal
      pulmonary exposure to traffic-related particles during pregnancy augments ozone
      induced airway hyperresponsiveness in offspring. METHODS: C57BL6 time-mated mice
      were given NIST SRM#1648 (particulate matter [PM]) 0.48 mg, saline vehicle, or no
      treatment by tracheal insufflation twice weekly for 3 weeks. PM exposure
      augmented maternal lung inflammation and placental TNF-alpha, Keratinocyte
      derived cytokine (KC), and IL-6 (measured at gestation Day 18). After
      parturition, dams and litters were exposed to air or ozone 1 ppm 3 h/d, every
      other day, thrice weekly for 4 weeks. Respiratory system resistance in pups was
      measured at baseline and after administration of nebulized methacholine.
      MEASUREMENTS AND MAIN RESULTS: Ozone increased airway hyperresponsiveness, but
      the increase was greatest in pups born to PM-treated dams. Whole-lung TNF-alpha,
      IL-1beta, KC, IL-6, and MCP-1 were increased in ozone-treated pups, with the
      greatest increase in pups born to dams given PM. Airway epithelial mucous
      metaplasia estimated by periodic acid-Schiff Alcian blue staining was increased
      in ozone-exposed pups born to PM-treated dams. Alveolar development, determined
      by morphometry, and airway smooth muscle bulk, estimated using alpha-actin
      histochemistry, were unaffected by prenatal or postnatal treatment. CONCLUSIONS:
      Maternal pulmonary exposure to PM during pregnancy augments placental cytokine
      expression and postnatal ozone-induced pulmonary inflammatory cytokine responses
      and ozone-induced airway hyperresponsiveness without altering airway structure.

PMID- 19762565
TI  - Increased propensity for central apnea in patients with obstructive sleep apnea:
      effect of nasal continuous positive airway pressure.
AB  - RATIONALE: There is increasing evidence of increased ventilatory instability in
      patients with obstructive sleep apnea (OSA), but previous investigations have not
      studied whether the hypocapnic apneic threshold is altered in this group.
      OBJECTIVES: To compare the apneic threshold, CO2 reserve, and controller gain
      between subjects with and without OSA matched for age, sex, and body mass index.
      METHODS: Hypocapnia was induced via nasal mechanical ventilation for 3 minutes.
      Cessation of mechanical ventilation resulted in hypocapnic central hypopnea or
      apnea depending upon the magnitude of the hypocapnia. The apnea threshold
      (Pet(CO2)-AT) was defined as the measured Pet(CO2) at which the apnea closest to
      the last hypopnea occurred. The CO2 reserve was defined as the change in Pet(CO2)
      between eupneic Pet(CO2) and Pet(CO2)-AT. Controller gain was defined as the
      ratio of change in Ve between control and hypopnea or apnea to the DeltaPet(CO2).
      MEASUREMENTS AND MAIN RESULTS: Eleven pairs of subjects were studied. There was
      no difference in the Pet(CO2)-AT between the two groups. However, the CO2 reserve
      was smaller in the subjects with OSA (2.2 +/- 0.6 mm Hg) compared with the
      control subjects (4.5 +/- 1.4 mm Hg; P < 0.001). The controller gain was
      increased in the subjects with OSA (3.7 +/- 1.3 L/min/mm Hg) compared with the
      control subjects (1.6 +/- 0.5 L/min/mm Hg; P < 0.001). Controller gain decreased
      and CO2 reserve increased in seven subjects restudied after using continuous
      positive airway pressure for 1 month. CONCLUSIONS: Ventilatory instability is
      increased in subjects with OSA and is reversible with the use of continuous
      positive airway pressure.

PMID- 19762566
TI  - Expression and role of myeloid-related protein-14 in clinical and experimental
      sepsis.
AB  - RATIONALE: Myeloid-related protein-8 (MRP8) and MRP14 can form heterodimers that
      elicit a variety of inflammatory responses. We showed that MRP8/14 is a ligand
      for Toll-like receptor-4, and that mice deficient in MRP8/14 are protected
      against endotoxic shock-induced lethality. OBJECTIVES: To determine (1) the
      extent of MRP8/14 release in patients with sepsis and/or peritonitis and in
      healthy humans exposed to LPS and (2) the contribution of MRP8/14 to the host
      response in murine abdominal sepsis. METHODS: MRP8/14 was measured in 51 patients
      with severe sepsis, 8 subjects after intravenous injection of LPS, and 17
      patients with peritonitis. Host responses to sepsis were compared in mrp14 gene
      deficient (and thereby MRP8/14-deficient) and wild-type mice intraperitoneally
      injected with Escherichia coli. MEASUREMENTS AND MAIN RESULTS: Patients with
      sepsis displayed elevated circulating MRP8/14 concentrations on both Days 0 and
      3, and LPS injection resulted in systemic MRP8/14 release in healthy humans. In
      patients with peritonitis, MRP8/14 levels in abdominal fluid were more than 15
      fold higher than in plasma. MRP14-deficient mice displayed improved defense
      against E. coli abdominal sepsis in an early phase, as indicated by diminished
      dissemination of the bacteria at 6 hours. In addition, MRP14-deficient mice
      demonstrated decreased systemic inflammation, as reflected by lower cytokine
      plasma concentrations, and less severe liver damage. CONCLUSIONS: Human sepsis
      and endotoxemia are associated with enhanced release of MRP8/14. In abdominal
      sepsis, MRP8/14 likely occurs primarily at the site of the infection,
      facilitating bacterial dissemination at an early phase and liver injury.

PMID- 19762567
TI  - Health leadership in sub-Saharan Africa.

PMID- 19762568
TI  - Does a preference for symphysiotomy over caesarean section reduce the operative
      delivery rate?
AB  - We analysed the data from a hospital that had practiced symphysiotomy and
      caesarean section (c/s) for many years and where symphysiotomy was acceptable to
      the parturient women, in order to determine the effects of symphysiotomy on c/s
      and on the overall operative delivery rates. Regression analysis revealed
      significant negative correlation between symphysiotomy and c/s (R = -0.610, P =
      0.03 at 95% confidence interval [CI]) and a non-significant negative correlation
      between symphysiotomy and combined operative deliveries (R = -0.108, P = 0.383 at
      5% CI). This study has confirmed that, in our environment, the practice of
      symphysiotomy significantly reduces the c/s rate and may save some women from
      operative deliveries in subsequent pregnancies. With the widespread aversion for
      c/s in the developing countries and a preference for symphysiotomy in some
      communities, symphysiotomy should be offered as an alternative to c/s whenever
      possible. Urgent revival of the dying skill of symphysiotomy is recommended in
      developing countries.

PMID- 19762569
TI  - Effectiveness of vaginal hysterectomy for benign conditions in semi-urban
      hospital: report from Maroua-Cameroon.
AB  - We assessed the effectiveness of vaginal hysterectomy for benign uterine
      conditions in Northern Cameroon. This is a case series study of 29 elective
      vaginal hysterectomies carried out between February 2005 and June 2007 in Maroua,
      Cameroon. Hysterocele was found as the only or associated indication in 17
      (58.6%) patients, symptomatic uterine fibroids in 4 (13.8%) and other indications
      in 8 (27.6%) patients. The mean duration of the operation was 132 minutes and the
      mean blood loss at surgery was 150 ml. Twenty-five of the 28 (89.3%) women had
      less than seven days of hospitalisation. There was a negative correlation (r = 
      0.45, P = 0.015) between duration of the surgery and the order of operation. One
      urinary tract and one wound infection were observed. Two patients had conversion
      to laparotomy. This study has shown that vaginal hysterectomy is a safe and
      feasible method of hysterectomy in a semi-urban hospital.

PMID- 19762570
TI  - Co-existence of TB and adult haematological cancers in Benin City, Nigeria.
AB  - Tuberculosis is an ancient human scourge that continues to be an important public
      health problem worldwide. As impaired immunity is closely associated with the
      pathogenesis of TB, an increase in the incidence of the disease among patients
      with cancer is anticipated. A total of 20 cases of haematological cancers co
      existing with TB in a tertiary hospital in an African setting between January
      2005 and September 2008 were analysed. Clinico-pathologic profiles, types of TB
      infection and outcome were noted. The incidence of TB in patients with
      haematological malignancies was 3.4%. Lymphoma and leukaemia were the most common
      malignancies associated with TB. With the high incidence of such cases we
      recommend the exclusion of an active disease prior to the initiation of cancer
      therapy. Chemoprophylaxis might be indicated in TB endemic areas.

PMID- 19762571
TI  - A comparative trial of three therapeutic regimens: ciprofloxacin-rifampin,
      ciprofloxacin-doxycycline and doxycycline-rifampin in the treatment of
      brucellosis.
AB  - This study was designed to compare the efficacy of ciprofloxacin plus rifampin
      (CR) and ciprofloxacin plus doxycycline (CD) versus doxycycline plus rifampin
      (DR) in the treatment of brucellosis. A total of 178 patients with brucellosis
      who were referred to the Sina Hospital, Hamedan, Iran, were included. The
      responses to therapy were observed in 166 cases (93.7%) - 59 were in the DR
      group, 59 in the CR group and 48 in the CD group. No significant differences in
      the therapeutic responses were observed (P = 0.09). Relapse was observed in 11.7%
      (DR 7.7%, CR 8.3% and CD 17.5%) after a six-month follow-up. No significant
      differences were also observed in relapse rates among the three groups (P =
      0.35). We concluded that DR is still the first choice regimen and CR or CD may be
      used as alternatives for treatment of brucellosis in adults.

PMID- 19762572
TI  - Prevalence of anaemia in the postpartum period: a study of a North Indian
      village.
AB  - Anaemia is a common public health problem but there is a paucity of studies
      regarding anaemia in the postpartum period. The objective of this study was to
      investigate the prevalence of anaemia in the postpartum period and factors
      associated with it. This prospective community-based study was carried out in a
      village of Haryana, India. Blood samples were collected for haemoglobin
      estimation at the end of six weeks postpartum. A total of 211 women were
      recruited and 168 women were included in the final analysis. It was found that
      70% of the study participants were anaemic (Hb < 11 g/dL). Only 37% of the
      population had consumed >/=90 iron folic acid (IFA) tablets. The mean haemoglobin
      level of women who had consumed >/=90 IFA tablets in the antepartum period was
      higher (10.43 g/dL) than those who consumed <90 IFA (9.9 g/dL). Multicentric
      studies are recommended to get the true picture for the whole country.

PMID- 19762573
TI  - Hepatic cystic echinococcosis: clinical characteristics and outcomes in Pakistan.
AB  - Hepatic cystic echinococcosis (HCE) is an emerging disease in central Asia,
      particularly in Pakistan, due to the migration of infected people. Medical
      records of patients with HCE admitted between 1995 and 2006 to a tertiary care
      hospital were reviewed. A total of 106 patients were admitted with a mean age of
      34+/-17 years; 60 (56.6%) were men, 72 (67.9%) were residing in rural areas of
      Pakistan and 21 (19.8%) were Afghan refugees. Twenty-seven (25.4%) had extra
      hepatic cysts and liver cysts. All patients received albendazole. Percutaneous
      aspiration, instillation and reaspirarion was done in 14 (13.2%) patients and 71
      (66.9%) underwent surgery. Three (2.8%) died and 14 (13.2%) had morbidity. This
      is one of the largest series of HCE reported from Pakistan. HCE is mostly
      prevalent in rural areas and among Afghan refugees with low mortality and
      recurrence, but with significant morbidity.

PMID- 19762574
TI  - Postoperative analgesia following caesarean deliveries in a rural health district
      of South Africa.
AB  - The under-treatment of postoperative pain is prevalent worldwide. This cross
      sectional study examined general practitioners' (GPs) knowledge and practices
      regarding postoperative analgesia in Caesarean deliveries. Postoperative
      analgesia was said to ensure that patients were pain-free (38.7%), achieved early
      mobilization (19.4%) and enabled early breast feeding (16%). Pethidine was the
      opioid of choice; normally prescribed eight hourly (69%) and was combined with
      non-steroidal anti-inflammatory drugs (NSAID) by 48.6% of doctors and used solely
      by 51.6%. The prescription of analgesics was mainly influenced by drug
      availability (45.2%) and potency (19.4%). Most doctors (93.5%) had never attended
      a pain management course or used pain scores. Doctors at level 1 hospitals were
      less likely to use pethidine in combination with NSAID (odds ratio: 0.11;
      confidence interval: 0.02-0.59) compared to those in the specialized hospital.
      The GPs recognized the importance of postoperative analgesia, but their practices
      made patients vulnerable to pain after caesarean section.

PMID- 19762575
TI  - What is the fate of the missing intrauterine contraceptive device?
AB  - An intrauterine contraceptive device (IUCD) is one of the most common forms of
      contraception in use worldwide today. It is associated with a myriad of problems
      and complications, one of which is the missing IUCD. It is a known fact that
      IUCDs can perforate the uterus resulting in its subsequent relocation in other
      organs within the pelvis and the abdomen. This study showed that more than 50% of
      clinically diagnosed cases of a missing IUCD are still located within the
      endometrial cavity. It is therefore being proposed that a clinical diagnosis of
      'missing string' be made until adequate radiological investigations, such as
      ultrasonography, plain X-rays and computerized tomography, have been carried out.

PMID- 19762576
TI  - Clinical features of patients with typhoid fever and drug resistance of the
      causative isolates in western Iran.
AB  - Typhoid fever is an important infectious disease in developing countries,
      including Iran. In this survey, all patients hospitalized in teaching hospitals
      of Hamedan during 1995-2005 were investigated. A total of 162 patients with
      typhoid fever were studied. Of all patients, 106 were male (65.4%). The most
      prevalent symptoms were fever (93.2%), chills (76.5%), anorexia (72.2%) and
      headache (71%). Splenomegaly and hepatomegaly were present in 43.8% and 13.6%,
      respectively. Salmonella typhi strains were identified in 144 patients (88.9%)
      and S. paratyphi A strains were found in 12 (7.4%). In others, S. paratyphi B and
      C were detected. Serum glutamic oxalo-acetic transaminase values were higher than
      normal in 77.5% of cases and serum glutamic pyruvic transaminase values were
      higher than normal in 62.5%. The highest sensitivity rate was for ceftizoxime,
      91.4% and the lowest rate was for ampicillin, 16.3%.

PMID- 19762577
TI  - Investigation of two outbreaks of suspected oral transmission of acute Chagas
      disease in the Amazon region, Para State, Brazil, in 2007.
AB  - Acute Chagas disease (ACD) is caused by Trypanosoma cruzi. ACD outbreaks due to
      probable oral transmission occur regularly in small family gatherings that are
      exposed to contaminated foods. We studied two cohorts of residents on islands in
      the Breves and Bagre municipalities, in July and August 2007, to identify risk
      factors of transmission and to recommend preventative measures. Of the 25 cases
      identified in both cohorts, 13 (52%) were men, and the most frequent symptoms
      were fever (96%),asthenia (80%), myalgia (76%), abdominal pain (64%), retro
      orbital pain, headaches and asthma (52%). We recommend detailed investigation of
      future outbreaks and other studies to better understand and control oral
      transmission of T. cruzi.

PMID- 19762578
TI  - Neurobrucellosis: an evaluation of a rare presentation of brucellosis from a
      tertiary care centre in Central Anatolia, Turkey.
AB  - Nervous system involvement is a rare manifestation of brucellosis. We describe
      our experience of the diagnosis, treatment and final outcome of patients with
      neurobrucellosis at the Erciyes University Gevher Nesibe Hospital, a tertiary
      referral centre in Central Anatolia, Turkey. Thirty-six adult patients were
      diagnosed with neurobrucellosis from January 1997 to December 2006. Headache and
      fever were the most common symptoms. Neck stiffness was present in 25 patients.
      Brucella spp was isolated from the blood of nine patients and from the
      cerebrospinal fluid of 11. Doxycycline (by mouth) plus rifampin (by mouth) with
      ceftriaxone (intravenously) were the most common treatment choices. Three
      patients died as a result of problems other than neurobrucellosis and relapse
      occurred in one patient. Neurobrucellosis presents with hetoregenous clinical
      signs.

PMID- 19762579
TI  - Prevalence of acanthosis nigricans and its correlates in a cross-section of
      Nigerians with type 2 diabetes mellitus.
AB  - Acanthosis nigricans (AN) is a dermatological condition that is often associated
      with obesity and may be a physical marker of insulin resistance. Studies have
      documented a high prevalence rate of AN in people with diabetes mellitus (DM).
      However, there have been no Nigerian reports on AN and DM. This report bridges
      the information gap and documents the prevalence of AN in Nigerians with type 2
      DM as well as its clinical correlates. Three hundred and forty consecutive
      subjects with type 2 DM were examined for the presence of AN and its associated
      clinical features. The prevalence of AN in type 2 DM in this report is 17%.
      Factors associated with AN include obesity, a family history of DM, female
      gender, the presence of hypertension and poor glycaemic control.

PMID- 19762580
TI  - Clinical and therapeutic aspects of childhood kerosene poisoning in Djibouti.
AB  - We report a prospective and descriptive study about childhood acute poisoning
      with kerosene in Djibouti. Acute poisoning is a common and stable occurrence in
      low socioeconomic groups in Africa, where negligence is the main cause of
      poisoning. The respiratory system was the main target, with 41% of patients
      having pneumonia, which may become life-threatening, but with low mortality rate.
      Asymptomatic patients (35%) can be discharged, while those with pulmonary or
      neurological signs must be admitted for observation and supportive treatment
      based on oxygen administration. Our study suggests management and provides a
      discussion for therapeutic options and emphasizes the importance of prevention.

PMID- 19762581
TI  - High maternal mortality and stillbirth in the Wad Medani Hospital, Central Sudan,
      2003-2007.
AB  - The aim of this study was to investigate the incidence and causes of maternal
      deaths and stillbirths at the Hospital of Obstetrics and Gynecology at Wad
      Medani, Sudan, from 1 January 2003 through 31 December 2007. All maternal deaths
      and stillbirths during this period were reviewed and classified retrospectively.
      There were 146 maternal deaths and 33034 live births, giving a maternal mortality
      ratio of 442/100,000 live births. The age range was 18-42 years with a mean
      (standard deviation) of 30.57 (5.26) years. The most common cause of death was
      septicaemia following obstructed labour or abortion-related sepsis, followed by
      haemorrhage, pre-eclampsia/ecalampsia, viral hepatitis and malaria. The
      stillbirth rate was 29/1000 births; the majority of which (8/1000) were macerated
      stillbirths.

PMID- 19762582
TI  - Altered consciousness in Ugandan hospital admissions.
AB  - An awareness of diseases causing altered mental status (AMS) in particular
      localities could greatly facilitate patient management. This cross-sectional
      study evaluated 100 consecutive patients with AMS admitted to a hospital in
      Uganda. Patients were assessed by the Confusion Assessment Method. History,
      examination, available laboratory tests and patients' response to treatment were
      used to identify aetiologies. Our study included 58 males and 42 females: 82%
      were 16-50 years old and 38% were HIV-infected. The most common cause of AMS was
      infection (51.3%), with cerebral malaria and meningitis predominating. The
      aetiology was unidentified in 12%. The in-hospital mortality rate was 44%, with
      HIV infection being positively associated. As infections and metabolic
      derangements, the most common causes of AMS in our setting, are mostly treatable
      with a relatively favourable outcome, critical evaluation, early intervention and
      improved investigative capacity would greatly improve patient outcome.

PMID- 19762583
TI  - Mid-trimester spontaneous uterine rupture.
AB  - The rupture of a uterus is still an enigmatic episode in obstetrics.
      Obstetricians may have to face it unexpectedly if it occurs spontaneously. Here,
      we report a case of a 20-year-old woman who presented to our out-patients
      department with abdominal pain and vaginal bleeding, and was diagnosed with a
      ruptured uterus.

PMID- 19762584
TI  - Ileosigmoid knotting- a rare variant of bowel volvulus.
AB  - Two patients with acute intestinal obstruction underwent exploratory laparotomy
      after adequate fluid resuscitation and radiological imaging. A preoperative
      diagnosis of sigmoid volvulus and an operative diagnosis of ileosigmoid knotting
      or compound volvulus were established.

PMID- 19762585
TI  - Disseminated histoplasmosis in an AIDS patient: a rare case from southern India.
AB  - We present a case of disseminated histoplasmosis with acquired immunodeficiency
      syndrome (AIDS). A 38-year-old woman presented with fever, cough, dysphagia,
      significant weight loss and a loss of appetite. She also suffered from anaemia
      and cervical lymphadenopathy. A lymph node biopsy and a bone marrow aspirate
      showed intracellular yeast forms of Histoplasma capsulatum. She improved with
      parenteral amphotericin B and oral itraconazole. Even though histoplasmosis is
      not endemic in South East Asia and India, it should be kept in mind when
      evaluating AIDS patients in view of the current scenario of the pandemic.

PMID- 19762586
TI  - Giant hydatid cyst of spleen: a case report.
AB  - Hydatidosis is endemic in many Mediterranean countries, the Middle East, South
      America, Australia, New Zealand and Africa. It is caused by an infection from the
      Echinococcus granulosus larvae which can lead to the development of cysts. The
      most frequently affected organ is the liver. Splenic involvement alone is very
      rare. In this article, a case of an isolated giant splenic hydatid cyst is
      reported. The patient underwent splenectomy. The diagnosis of a hydatid cyst was
      confirmed by histopathology. This case suggests that hydatid disease should be
      considered as a differential diagnosis in every patient with a cystic mass of the
      spleen in endemic areas.

PMID- 19762587
TI  - Adenomyosis and uterine rupture during labour in a primigravida: an unusual
      obstetric emergency in Nigeria.
AB  - The primigravid uterus is believed to be immune to rupture during labour. This
      may not be true for those who have had prior adenomyomectomy, hence this report.
      The patient was a 28-year-old nullipara who became pregnant 11 months after an
      adenomyomectomy. Twelve hours after vaginal delivery at term, she developed
      haemoperitoneum of unclear cause. Emergency laparotomy and subsequent histology
      showed a fundal complete uterine rupture through the adenomyomectomy site, which
      was repaired. It is concluded that adenomyomectomy predisposes a pregnant uterus
      to rupture during labour. Therefore, such women should be offered elective
      caesarean delivery at term.

PMID- 19762588
TI  - A case of Brucella endocarditis in association with superficial femoral artery
      thrombus.
AB  - We report here a case of Brucella endocarditis associated with superficial
      femoral artery thrombus. The patient was treated only with medical treatment. The
      clinical significance of the case was the presence of two rare complications of
      brucellosis:endocarditis and arterial thrombus.

PMID- 19762589
TI  - Invading plant material appearing as a colonic tumoural mass in a four-year-old
      girl.
AB  - In this article, we report the invasive behaviour of a plant, not described
      before, which elicited a severe inflammatory response in the colonic wall, and
      was clinically diagnosed as a mass lesion in a four-year-old girl. Although
      rectal bezoars are the most frequent complications of ingested dried seeds, this
      plant behaviour should also be borne in mind in rare occassions.

PMID- 19762590
TI  - Abdominal cocoon in an adolescent male patient.
AB  - Abdominal cocoon is a rare cause of bowel obstruction. The condition was first
      described three decades ago and is found mainly among adolescent females in
      tropical and sub-tropical countries. It is characterized by a thick fibrous
      membrane encapsulating the small intestines partially or completely. Patients
      present with features of intestinal obstruction and diagnosis is usually made
      intraoperatively. Surgical excision of the membrane and adhesiolysis result in
      complete recovery. We report on an adolescent male patient who had acute
      intestinal obstruction due to abdominal cocoon detected at surgery.

PMID- 19762591
TI  - A novel biomarker-guided immunomodulatory approach for the therapy of sepsis.

PMID- 19762592
TI  - Biomass-fueled intervention stoves in the developing world: potential and
      challenges.

PMID- 19762593
TI  - Endoscopic interventions in severe emphysema.

PMID- 19762594
TI  - Reactivity to mycobacterial antigens by patients with Lofgren's syndrome as a
      model of phenotypic susceptibility to disease and disease progression.

PMID- 19762595
TI  - Should moxifloxacin be substituted for isoniazid as a first-line antituberculosis
      drug?

PMID- 19762596
TI  - Control of iron homeostasis by an iron-regulated ubiquitin ligase.
AB  - Eukaryotic cells require iron for survival and have developed regulatory
      mechanisms for maintaining appropriate intracellular iron concentrations. The
      degradation of iron regulatory protein 2 (IRP2) in iron-replete cells is a key
      event in this pathway, but the E3 ubiquitin ligase responsible for its
      proteolysis has remained elusive. We found that a SKP1-CUL1-FBXL5 ubiquitin
      ligase protein complex associates with and promotes the iron-dependent
      ubiquitination and degradation of IRP2. The F-box substrate adaptor protein FBXL5
      was degraded upon iron and oxygen depletion in a process that required an iron
      binding hemerythrin-like domain in its N terminus. Thus, iron homeostasis is
      regulated by a proteolytic pathway that couples IRP2 degradation to intracellular
      iron levels through the stability and activity of FBXL5.

PMID- 19762597
TI  - An E3 ligase possessing an iron-responsive hemerythrin domain is a regulator of
      iron homeostasis.
AB  - Cellular iron homeostasis is maintained by the coordinate posttranscriptional
      regulation of genes responsible for iron uptake, release, use, and storage
      through the actions of the iron regulatory proteins IRP1 and IRP2. However, the
      manner in which iron levels are sensed to affect IRP2 activity is poorly
      understood. We found that an E3 ubiquitin ligase complex containing the FBXL5
      protein targets IRP2 for proteasomal degradation. The stability of FBXL5 itself
      was regulated, accumulating under iron- and oxygen-replete conditions and
      degraded upon iron depletion. FBXL5 contains an iron- and oxygen-binding
      hemerythrin domain that acted as a ligand-dependent regulatory switch mediating
      FBXL5's differential stability. These observations suggest a mechanistic link
      between iron sensing via the FBXL5 hemerythrin domain, IRP2 regulation, and
      cellular responses to maintain mammalian iron homeostasis.

PMID- 19762598
TI  - Three-color entanglement.
AB  - Entanglement is an essential quantum resource for the acceleration of information
      processing as well as for sophisticated quantum communication protocols. Quantum
      information networks are expected to convey information from one place to another
      by using entangled light beams. We demonstrated the generation of entanglement
      among three bright beams of light, all of different wavelengths (532.251,
      1062.102, and 1066.915 nanometers). We also observed disentanglement for finite
      channel losses, the continuous variable counterpart to entanglement sudden death.

PMID- 19762599
TI  - Tyrannosaurid skeletal design first evolved at small body size.
AB  - Nearly all of the large-bodied predators (>2.5 tons) on northern continents
      during the Late Cretaceous were tyrannosaurid dinosaurs. We show that their most
      conspicuous functional specializations--a proportionately large skull, incisiform
      premaxillary teeth, expanded jaw-closing musculature, diminutive forelimbs, and
      hindlimbs with cursorial proportions--were present in a new, small-bodied, basal
      tyrannosauroid from Lower Cretaceous rocks in northeastern China. These
      specializations, which were later scaled up in Late Cretaceous tyrannosaurids
      with body masses approaching 100 times greater, drove the most dominant radiation
      of macropredators of the Mesozoic.

PMID- 19762600
TI  - Similar renal decline in diabetic and non-diabetic patients with comparable
      levels of albuminuria.
AB  - BACKGROUND: Diabetes is the main cause of ESRD, and albuminuria is a major
      determinant of adverse renal outcome. Likewise, albuminuria is an intermediate
      risk factor of chronic kidney disease (CKD) progression in diabetic patients. Our
      aim was to compare the rate of renal decline in diabetic and non-diabetic CKD
      patients (GFR < 50 ml/min) with comparable levels of albuminuria. METHODS: In
      this observational study, 333 patients (age 67 +/- 15 years, 46% diabetics) were
      included during a 7.5-year period. The mean follow-up was 30 +/- 18 months (range
      4-79). The influence of study variables was evaluated applying a time-dependent
      Cox model and slope-based outcome using a linear regression model. RESULTS: The
      diabetes condition was associated with adverse outcome in univariate analysis,
      and after adjusting for age, sex and systolic blood pressure. However, when
      controlling for albuminuria (a time-dependent covariate), diabetes did not show
      any association with outcome. In addition, the mean slope of renal decline was
      similar in diabetic and non-diabetic patients when controlling for albuminuria.
      The urinary albumin-creatinine ratio was a robust predictor of poor outcome in
      uni- and multivariate models. In the diabetic group, time-varying glycosilated
      haemoglobin did not influence renal outcome in the Cox model, and time-varying
      albuminuria remained a strong predictor of outcome. CONCLUSIONS: Diabetic
      patients have a poorer renal outcome, but at comparable levels of albuminuria
      renal decline is similar in diabetic and non-diabetic patients. Albuminuria is a
      risk factor for renal decline, and the main target to delay progression in
      patients, diabetics or non-diabetics, with moderate to advanced CKD.

PMID- 19762601
TI  - Dual blockade of the renin-angiotensin system: are two better than one?

PMID- 19762602
TI  - Nocturnal haemodialysis is associated with improved vascular smooth muscle cell
      biology.
AB  - BACKGROUND: Conventional haemodialysis (CHD) is associated with a reduction in
      vascular smooth muscle cells (VSMCs) proliferation and an increase in apoptosis.
      METHODS: VSMC proliferation, migration, apoptosis and Runx2 expression were
      assessed under normal conditions (n = 4) and before and after conversion from CHD
      to NHD (n = 15). RESULTS: Compared to normal, CHD is associated with a reduction
      in VSMC proliferation [0.49 +/- 0.07 (CHD) versus 1.34 +/- 0.02 RFU, P < 0.01],
      an augmented caspase-3 activity [0.30 +/- 0.02 (CHD) versus 0.22 +/- 0.02 RFU, P
      = 0.014] and a 1.4 +/- 0.3 fold increase in Runx2 expression. After conversion to
      NHD, VSMC proliferation was higher than during CHD [from 0.49 +/- 0.07 (CHD) to
      0.68 +/- 0.09 RFU, P = 0.006] and approached that of controls (1.34 +/- 0.02, P >
      0.05). Caspase-3 activity was restored to similar values as controls [0.26 +/-
      0.02 (NHD) versus 0.22 +/- 0.04 (normal), P > 0.05]. Runx2 expression decreased
      to similar levels as normal controls. NHD enhanced dialysis dose delivery,
      lowered blood pressure, plasma parathyroid hormone levels and normalized plasma
      phosphate (from 1.7 +/- 0.1 to 1.2 +/- 0.1 mmol/L, P < 0.01). The reduction in
      plasma phosphate correlated with the change in VSMC proliferation (r = -0.71, P =
      0.007). CONCLUSIONS: We demonstrate that NHD is associated with restoration of
      abnormal VSMC biology in ESRD. Given the increasing importance of VSMCs in the
      pathogenesis of atherosclerosis and medial calcification, these data may have
      important implications for vascular risk in ESRD patients.

PMID- 19762603
TI  - Abdominal fat deposition is associated with increased inflammation, protein
      energy wasting and worse outcome in patients undergoing haemodialysis.
AB  - OBJECTIVE: The role of obesity in promoting or preventing the complications of
      haemodialysis patients remains unclear, with several studies suggesting that
      obesity may even be beneficial. We tested the hypothesis that abdominal fat
      deposition in HD patients is a risk factor associated with both increased
      inflammation and protein-energy wasting (PEW), as well as elevated mortality
      risk. METHODS: A cross-sectional study with mortality follow-up [median 41
      (interquartile range 25-47) months] of haemodialysis patients [n = 173, 100 men,
      aged 65 (51-74) years]. Abdominal fat deposition was assessed by means of a
      conicity index (Ci), which estimates fat accumulation in the abdomen as the
      deviation of body shape from a cylindrical towards a double-cone shape (i.e. two
      cones with a common base at the waist level). The Ci was studied with regard to
      baseline inflammatory, anthropometric and nutritional markers, including
      subjective global assessment (SGA). RESULTS: Across increasing tertiles of the
      Ci, patients were older, fatter and more inflamed (P < 0.01 for all). At the same
      time, they presented a higher prevalence of PEW (SGA >1), reduced handgrip
      strength and lower S-creatinine (P < 0.01 for all). An increased abdominal fat
      deposition was associated with worse outcome independently of age, sex,
      comorbidities and dialysis vintage [Cox HR 1.93 (95% CI = 1.06-3.49)], but the
      predictive value disappeared following adjustment for interleukin-6 (IL-6) and
      PEW. CONCLUSION: Abdominal fat deposition in haemodialysis patients is linked to
      both inflammation and PEW, resulting in an increased mortality risk. Our results
      support the idea that regional differences in adiposity accumulation may have
      diverse implications on patient outcome.

PMID- 19762604
TI  - Chronic kidney disease in long-term survivors of myeloablative allogeneic
      haematopoietic cell transplantation: prevalence and risk factors.
AB  - BACKGROUND: Chronic kidney disease (CKD) seems to be common in long-term
      survivors of haematopoietic cell transplantation (HCT). However, the range of its
      frequency is very wide, likely due to variability in the definitions of CKD and
      the periods of follow-up. METHODS: We conducted a cross-sectional and
      retrospective study in 158 adults who received myeloablative allogeneic HCT for
      lymphohaematologic malignancies at least 3 years ago and are alive today. The
      mean survival time was 6.15 +/- 4.88 years (range: 3-16 years). CKD was defined
      as a sustained decrease in glomerular filtration rate (GFR) or persistent
      proteinuria for a period more than 3 months. GFR was calculated based on serum
      creatinine (Cr) using the Modification of Diet in Renal Disease formula. Serum Cr
      and proteinuria were measured at least on three occasions separated by one or
      more months before the investigation. CKD was classified according to the
      National Kidney Foundation CKD staging. Proteinuria was defined as positive
      dipstick test > or =1+. The factors associated with the presence of CKD with a
      decrease of GFR (CKD > or = stage 3) were examined using multivariate logistic
      regression analysis, adjusted for demographic and clinical characteristics.
      RESULTS: The prevalence of proteinuria was found in 36 out of 158 patients
      (22.8%). The prevalence of each CKD stage was as follows: Stage 0 (no CKD), 98
      patients (62.0%); Stage 1, 18 patients (11.4%); Stage 2, 15 patients (9.5%);
      Stage 3, 8 patients (5.1%); Stage 4, 10 patients (6.3%) and Stage 5, 9 patients
      (5.7%). Initiation of chronic dialysis treatment or transplant was performed in
      seven CKD stage-5 patients (4.4%) at a mean of 10.9 +/- 3.72 years after HCT.
      Multivariate analysis identified acute kidney injury with HCT [odds ratio (OR),
      9.920; 95% confidence interval (CI), 2.084-39.68; P = 0.0051], hypertension after
      HCT (OR, 4.031; 95% CI, 1.044-13.06; P = 0.0346) and survival time after HCT (OR,
      4.275; 95% CI, 2.823-23.04; P = 0.0481) as significant factors associated with
      the presence of CKD > or = stage 3. CONCLUSIONS: A remarkably high percentage of
      long-term survivors had evidence of proteinuria and all stages of CKD. CKD in
      transplant recipients may result from incomplete recovery from acute renal
      insults, hypertension and increasing longevity. The CKD cohort should be at a
      great risk for end-stage renal disease and cardiovascular morbidity and
      mortality. The burden of CKD should be recognized as a significant public health
      problem.

PMID- 19762605
TI  - Body composition in home haemodialysis versus conventional haemodialysis: a cross
      sectional, matched, comparative study.
AB  - BACKGROUND: Nutritional status predicts outcome in dialysis populations.
      Increased dialysis time and/or frequency reportedly improves nutritional status.
      We examined the impact of more intensive dialysis on body composition. METHODS: A
      cross-sectional, matched study comparing home haemodialysis (HHD) patients (>15
      h/week, n = 28) and conventional haemodialysis (CHD) patients (<15 h/ week, n =
      28), matched for age, sex, length of time on dialysis and diabetes, was
      performed. We measured total body protein (TBP) by in vivo neutron activation,
      total body fat (TBF) and skeletal muscle mass (SKMM) by dual-energy x-ray
      absorptiometry (DEXA) and biochemical and inflammatory parameters. Visceral (VFA)
      and subcutaneous fat areas (SFA) were determined from computed tomography.
      RESULTS: There was no significant difference in TBP (10.2 +/- 1.9 kg CHD versus
      10.8 +/- 1.8 kg HHD, P = 0.18) or SKMM (25.6 +/- 5.6 kg CHD versus 26.2 +/- 4.2
      kg HHD). TBF was not different (27.7 +/- 10.7 kg CHD versus 27.8 +/- 16.0 kg
      HHD), although the HHD group had greater VFA (182.0 +/- 105.6 cm(2) versus 173.8
      +/- 90.1 cm(2)) and lower SFA (306.7 +/- 176.4 cm(2) versus 309.7 +/- 138.1
      cm(2)), the difference was not statistically significant. Albumin concentrations
      were significantly increased in the HHD group (37.5 +/- 3.56 g/L versus 35.18 +/-
      4.11 g/L, P = 0.03), whilst phosphate concentrations (1.57 +/- 0.41 mmol/LHHD
      versus 1.92 +/- 0.62 mmol/ LCHD, P = 0.02) and inflammatory parameters were
      lower. There was a positive relationship between hours of dialysis and TBP (beta
      = 0.08; P = 0.03). CONCLUSION: Surrogate nutritional markers and inflammatory
      parameters improved with more intensive dialysis, but this was not reflected by
      improved body composition. Further prospective studies are required to confirm
      whether more intensive dialysis affects body composition, and whether this
      impacts on metabolic risk and clinical outcome.

PMID- 19762606
TI  - Prescribing peritoneal dialysis in each patient with uremic toxins as the
      treatment marker.

PMID- 19762607
TI  - Might there be an association between polycystic kidney disease and noncompaction
      of the ventricular myocardium?
AB  - We report on a paediatric case of autosomal dominant polycystic kidney disease,
      where myocardial hypertrophy proved a consequence of noncompaction of the
      ventricular myocardium. Deletion of PKD1 and PKD2, the genes responsible for
      polycystic renal disease, has been linked also to disorganized myocardial
      arrangement in experimental animals. Two adults with polycystic kidney disease
      and myocardial hypertrophy in whom a careful diagnostic workup led to a diagnosis
      of non-compaction of the ventricular myocardium have been reported in the
      literature. Nephrologists must be aware of the possible association between the
      two diseases because early recognition of the disease may help in preventing the
      onset of complications.

PMID- 19762608
TI  - Clinical implication of metabolic syndrome on chronic kidney disease depends on
      gender and menopausal status: results from the Korean National Health and
      Nutrition Examination Survey.
AB  - BACKGROUND: The prevalence of chronic kidney disease (CKD) has been increasing
      throughout the world over the last decade. Metabolic syndrome (MS) has been known
      to be an independent risk factor of CKD. However, both renal and metabolic
      diseases are experienced differently in men and women, and clinical implication
      of MS on CKD may be different according to gender. METHODS: To understand the
      association between MS and CKD, we performed a cross-sectional study in non
      institutionalized civilians using the data of the Korean National Health and
      Nutrition Examination Survey. Of 37 769 participants, 5091 were available for the
      analysis of the prevalence of CKD (defined as dipstick proteinuria or a reduced
      GFR < 60 ml/min/1.73 m(2)). RESULTS: The prevalence of CKD was 8.9% (7.4% in men,
      4.7% in premenopausal women and 20.1% in postmenopausal women) and MS was seen in
      26.2% (24.9% in men, 13.9% in premenopausal women and 52% in postmenopausal
      women). The prevalence of CKD increased with ageing, in particular after sharply
      after the age of 50 in both genders. MS was a significant determinant of CKD;
      however, sub-analysis revealed that MS was a risk factor for CKD only in men
      under the age of 60 and in postmenopausal women. Neither MS per se nor individual
      components of MS were associated with CKD in men over the age of 60 and in
      premenopausal women. CONCLUSION: Differential effect of MS on CKD according to
      age and gender in our study may provide a clue to define the subject in need for
      more attention for the treatment of MS in terms of the development of CKD.

PMID- 19762609
TI  - Biodiversity policy challenges.

PMID- 19762611
TI  - Research awards. Laskers honor five scientists and a mayor.

PMID- 19762610
TI  - Swine flu outbreak. China first to vaccinate against novel H1N1 virus.

PMID- 19762612
TI  - Biotechnology. Researcher, two universities sued over validity of prostate cancer
      test.

PMID- 19762614
TI  - Materials science. DuPont scientist accused of stealing company's trade secrets.

PMID- 19762615
TI  - Scientific publishing. PNAS nixes special privileges for (most) papers.

PMID- 19762616
TI  - Scientific publishing. Paper retracted following genome data breach.

PMID- 19762617
TI  - U.S. science education. Revisions to AP courses expected to have domino effect.

PMID- 19762619
TI  - Low-income countries. A boost for vaccine development.

PMID- 19762621
TI  - Astronomy. Scrambling to read the meaning of the sky's most ancient flare.

PMID- 19762620
TI  - A cure for euthanasia?

PMID- 19762622
TI  - Tenure: incentivize faculty.

PMID- 19762623
TI  - Tenure: expiration time.

PMID- 19762624
TI  - Tenure: where to draw the line.

PMID- 19762626
TI  - Increase grants, too.

PMID- 19762627
TI  - Comment on "The dynamic control of kiss-and-run and vesicular reuse probed with
      single nanoparticles".
AB  - Zhang et al. (Research Articles, 13 March 2009, p. 1448) reported that synaptic
      vesicles usually release neurotransmitter through a kiss-and-run mechanism
      occurring within 1 second but that full collapse of the vesicles becomes more
      prevalent with repeated stimuli. We report that the kinetics of vesicle retrieval
      do not change during a stimulus train, with endocytosis occurring in 10 to 15
      seconds.

PMID- 19762628
TI  - Stable funding is key.

PMID- 19762629
TI  - Ecology. Biodiversity conservation and the Millennium Development Goals.

PMID- 19762630
TI  - Ecology. Tracking progress toward the 2010 biodiversity target and beyond.

PMID- 19762631
TI  - Cell biology. Expanding functionality within the looking-glass universe.

PMID- 19762632
TI  - Ecology. Seeing the big picture on microbe distribution.

PMID- 19762633
TI  - Physics. Itinerant ferromagnetism with ultracold atoms.

PMID- 19762634
TI  - Geophysics. How river beds move.

PMID- 19762635
TI  - Physics. The super of superradiance.

PMID- 19762636
TI  - Macroevolution of complex retroviruses.
AB  - Retroviruses can leave a "fossil record" in their hosts' genomes in the form of
      endogenous retroviruses. Foamy viruses, complex retroviruses that infect mammals,
      have been notably absent from this record. We have found an endogenous foamy
      virus within the genomes of sloths and show that foamy viruses were infecting
      mammals more than 100 million years ago and codiverged with their hosts across an
      entire geological era. Our analysis highlights the role of evolutionary
      constraint in maintaining viral genome structure and indicates that accessory
      genes and mammalian mechanisms of innate immunity are the products of
      macroevolutionary conflict played out over a geological time scale.

PMID- 19762637
TI  - Control of spin precession in a spin-injected field effect transistor.
AB  - Spintronics increases the functionality of information processing while seeking
      to overcome some of the limitations of conventional electronics. The spin
      injected field effect transistor, a lateral semiconducting channel with two
      ferromagnetic electrodes, lies at the foundation of spintronics research. We
      demonstrated a spin-injected field effect transistor in a high-mobility InAs
      heterostructure with empirically calibrated electrical injection and detection of
      ballistic spin-polarized electrons. We observed and fit to theory an oscillatory
      channel conductance as a function of monotonically increasing gate voltage.

PMID- 19762638
TI  - Itinerant ferromagnetism in a Fermi gas of ultracold atoms.
AB  - Can a gas of spin-up and spin-down fermions become ferromagnetic because of
      repulsive interactions? We addressed this question, for which there is not yet a
      definitive theoretical answer, in an experiment with an ultracold two-component
      Fermi gas. The observation of nonmonotonic behavior of lifetime, kinetic energy,
      and size for increasing repulsive interactions provides strong evidence for a
      phase transition to a ferromagnetic state. Our observations imply that itinerant
      ferromagnetism of delocalized fermions is possible without lattice and band
      structure, and our data validate the most basic model for ferromagnetism
      introduced by Stoner.

PMID- 19762639
TI  - An anomalous basaltic meteorite from the innermost main belt.
AB  - Triangulated observations of fireballs allow us to determine orbits and fall
      positions for meteorites. The great majority of basaltic meteorites are derived
      from the asteroid 4 Vesta. We report on a recent fall that has orbital properties
      and an oxygen isotope composition that suggest a distinct parent body. Although
      its orbit was almost entirely contained within Earth's orbit, modeling indicates
      that it originated from the innermost main belt. Because the meteorite parent
      body would likely be classified as a V-type asteroid, V-type precursors for
      basaltic meteorites unrelated to Vesta may reside in the inner main belt. This
      starting location is in agreement with predictions of a planetesimal evolution
      model that postulates the formation of differentiated asteroids in the
      terrestrial planet region, with surviving fragments concentrated in the innermost
      main belt.

PMID- 19762640
TI  - Attitudes and action: public opinion and the occurrence of international
      terrorism.
AB  - The predictors of terrorism are unclear. This paper examines the effect of public
      opinion in one country toward another country on the number of terrorist attacks
      perpetrated by people or groups from the former country against targets in the
      latter country. Public opinion was measured by the percentage of people in Middle
      Eastern and North African countries who disapprove of the leadership of nine
      world powers. Count models for 143 pairs of countries were used to estimate the
      effect of public opinion on terrorist incidents, controlling for other relevant
      variables and origin-country fixed effects. We found a greater incidence of
      international terrorism when people of one country disapprove of the leadership
      of another country.

PMID- 19762641
TI  - Highly variable spread rates in replicated biological invasions: fundamental
      limits to predictability.
AB  - Although mean rates of spread for invasive species have been intensively studied,
      variance in spread rates has been neglected. Variance in spread rates can be
      driven exogenously by environmental variability or endogenously by demographic or
      genetic stochasticity in reproduction, survival, and dispersal. Endogenous
      variability is likely to be important in spread but has not been studied
      empirically. We show that endogenously generated variance in spread rates is
      remarkably high between replicated invasions of the flour beetle Tribolium
      castaneum in laboratory microcosms. The observed variation between replicate
      invasions cannot be explained by demographic stochasticity alone, which indicates
      inherent limitations to predictability in even the simplest ecological settings.

PMID- 19762642
TI  - Controls on diatom biogeography in the ocean.
AB  - The extent to which the spatial distribution of marine planktonic microbes is
      controlled by local environmental selection or dispersal is poorly understood.
      Our ability to separate the effects of these two biogeographic controls is
      limited by the enormous environmental variability both in space and through time.
      To circumvent this limitation, we analyzed fossil diatom assemblages over the
      past ~1.5 million years from the world oceans and show that these eukaryotic
      microbes are not limited by dispersal. The lack of dispersal limitation in marine
      diatoms suggests that the biodiversity at the microbial level fundamentally
      differs from that of macroscopic animals and plants for which geographic
      isolation is a common component of speciation.

PMID- 19762643
TI  - A constant flux of diverse thermophilic bacteria into the cold Arctic seabed.
AB  - Microorganisms have been repeatedly discovered in environments that do not
      support their metabolic activity. Identifying and quantifying these misplaced
      organisms can reveal dispersal mechanisms that shape natural microbial diversity.
      Using endospore germination experiments, we estimated a stable supply of
      thermophilic bacteria into permanently cold Arctic marine sediment at a rate
      exceeding 10(8) spores per square meter per year. These metabolically and
      phylogenetically diverse Firmicutes show no detectable activity at cold in situ
      temperatures but rapidly mineralize organic matter by hydrolysis, fermentation,
      and sulfate reduction upon induction at 50 degrees C. The closest relatives to
      these bacteria come from warm subsurface petroleum reservoir and ocean crust
      ecosystems, suggesting that seabed fluid flow from these environments is
      delivering thermophiles to the cold ocean. These transport pathways may broadly
      influence microbial community composition in the marine environment.

PMID- 19762644
TI  - Three-dimensional structural view of the central metabolic network of Thermotoga
      maritima.
AB  - Metabolic pathways have traditionally been described in terms of biochemical
      reactions and metabolites. With the use of structural genomics and systems
      biology, we generated a three-dimensional reconstruction of the central metabolic
      network of the bacterium Thermotoga maritima. The network encompassed 478
      proteins, of which 120 were determined by experiment and 358 were modeled.
      Structural analysis revealed that proteins forming the network are dominated by a
      small number (only 182) of basic shapes (folds) performing diverse but mostly
      related functions. Most of these folds are already present in the essential core
      (approximately 30%) of the network, and its expansion by nonessential proteins is
      achieved with relatively few additional folds. Thus, integration of structural
      data with networks analysis generates insight into the function, mechanism, and
      evolution of biological networks.

PMID- 19762645
TI  - Details of insect wing design and deformation enhance aerodynamic function and
      flight efficiency.
AB  - Insect wings are complex structures that deform dramatically in flight. We
      analyzed the aerodynamic consequences of wing deformation in locusts using a
      three-dimensional computational fluid dynamics simulation based on detailed wing
      kinematics. We validated the simulation against smoke visualizations and digital
      particle image velocimetry on real locusts. We then used the validated model to
      explore the effects of wing topography and deformation, first by removing camber
      while keeping the same time-varying twist distribution, and second by removing
      camber and spanwise twist. The full-fidelity model achieved greater power economy
      than the uncambered model, which performed better than the untwisted model,
      showing that the details of insect wing topography and deformation are important
      aerodynamically. Such details are likely to be important in engineering
      applications of flapping flight.

PMID- 19762646
TI  - D-amino acids govern stationary phase cell wall remodeling in bacteria.
AB  - In all known organisms, amino acids are predominantly thought to be synthesized
      and used as their L-enantiomers. Here, we found that bacteria produce diverse D
      amino acids as well, which accumulate at millimolar concentrations in
      supernatants of stationary phase cultures. In Vibrio cholerae, a dedicated
      racemase produced D-Met and D-Leu, whereas Bacillus subtilis generated D-Tyr and
      D-Phe. These unusual D-amino acids appear to modulate synthesis of peptidoglycan,
      a strong and elastic polymer that serves as the stress-bearing component of the
      bacterial cell wall. D-Amino acids influenced peptidoglycan composition, amount,
      and strength, both by means of their incorporation into the polymer and by
      regulating enzymes that synthesize and modify it. Thus, synthesis of D-amino
      acids may be a common strategy for bacteria to adapt to changing environmental
      conditions.

PMID- 19762648
TI  - Why is water an issue?

PMID- 19762649
TI  - Prior reports of medical problems among inmates.

PMID- 19762650
TI  - Simplifying consent increases HIV testing and new case detection: the San
      Francisco experience.

PMID- 19762651
TI  - The benefits of risk factor prevention in Americans aged 51 years and older.
AB  - OBJECTIVES: We assessed the potential health and economic benefits of reducing
      common risk factors in older Americans. METHODS: A dynamic simulation model
      tracked a national cohort of persons 51 and 52 years of age to project their
      health and medical spending in prevention scenarios for diabetes, hypertension,
      obesity, and smoking. RESULTS: The gain in life span from successful treatment of
      a person aged 51 or 52 years for obesity would be 0.85 years; for hypertension,
      2.05 years; and for diabetes, 3.17 years. A 51- or 52-year-old person who quit
      smoking would gain 3.44 years. Despite living longer, those successfully treated
      for obesity, hypertension, or diabetes would have lower lifetime medical
      spending, exclusive of prevention costs. Smoking cessation would lead to
      increased lifetime spending. We used traditional valuations for a life-year to
      calculate that successful treatments would be worth, per capita, $198,018
      (diabetes), $137,964 (hypertension), $118,946 (smoking), and $51,750 (obesity).
      CONCLUSIONS: Effective prevention could substantially improve the health of older
      Americans, and--despite increases in longevity--such benefits could be achieved
      with little or no additional lifetime medical spending.

PMID- 19762652
TI  - Eliminating health disparities through transdisciplinary research, cross-agency
      collaboration, and public participation.
AB  - Despite efforts to the contrary, disparities in health and health care persist in
      the United States. To solve this problem, federal agencies representing different
      disciplines and perspectives are collaborating on a variety of transdisciplinary
      research initiatives. The most recent of these initiatives was launched in 2006
      when the Centers for Disease Control and Prevention's Office of Public Health
      Research and the Department of Health and Human Services' Office of Minority
      Health brought together federal partners representing a variety of disciplines to
      form the Federal Collaboration on Health Disparities Research (FCHDR). FCHDR
      collaborates with a wide variety of federal and nonfederal partners to support
      and disseminate research that aims to reduce or eliminate disparities in health
      and health care. Given the complexity involved in eliminating health disparities,
      there is a need for more transdisciplinary, collaborative research, and
      facilitating that research is FCHDR's mission.

PMID- 19762653
TI  - Collaborating to end health disparities in our lifetime.

PMID- 19762654
TI  - Implementing evidence-based practice in community mental health agencies: a
      multiple stakeholder analysis.
AB  - OBJECTIVES: We sought to identify factors believed to facilitate or hinder
      evidence-based practice (EBP) implementation in public mental health service
      systems as a step in developing theory to be tested in future studies. METHODS:
      Focusing across levels of an entire large public sector mental health service
      system for youths, we engaged participants from 6 stakeholder groups: county
      officials, agency directors, program managers, clinical staff, administrative
      staff, and consumers. RESULTS: Participants generated 105 unique statements
      identifying implementation barriers and facilitators. Participants rated each
      statement on importance and changeability (i.e., the degree to which each barrier
      or facilitator is considered changeable). Data analyses distilled statements into
      14 factors or dimensions. Descriptive analyses suggest that perceptions of
      importance and changeability varied across stakeholder groups. CONCLUSIONS:
      Implementation of EBP is a complex process. Cross-system-level approaches are
      needed to bring divergent and convergent perspectives to light. Examples include
      agency and program directors facilitating EBP implementation by supporting staff,
      actively sharing information with policymakers and administrators about EBP
      effectiveness and fit with clients' needs and preferences, and helping clinicians
      to present and deliver EBPs and address consumer concerns.

PMID- 19762655
TI  - Childhood socioeconomic position and disability in later life: results of the
      health and retirement study.
AB  - OBJECTIVES: We used a life course approach to assess the ways in which childhood
      socioeconomic position may be associated with disability in later life. METHODS:
      We used longitudinal data from the nationally representative Health and
      Retirement Study (1998-2006) to examine associations between parental education,
      paternal occupation, and disabilities relating to activities of daily living
      (ADLs) and instrumental activities of daily living (IADLs). RESULTS: Respondents
      whose fathers had low levels of education and those whose fathers were absent or
      had died while they were growing up were at increased risk of disability in later
      life, net of social, behavioral, and pathological health risks in adulthood.
      Social mobility and health behaviors were also important factors in the
      association between low childhood socioeconomic position and ADL and IADL
      disabilities. CONCLUSIONS: Our findings highlight the need for policies and
      programs aimed at improving the well-being of both children and families. A
      renewed commitment to such initiatives may help reduce health care costs and the
      need for people to use health and social services in later life.

PMID- 19762656
TI  - Association between widowhood and risk of diagnosis with a sexually transmitted
      infection in older adults.
AB  - OBJECTIVES: We assessed whether widowhood is associated with risk of diagnosis
      with a sexually transmitted infection (STI) among older adults in the United
      States and whether the associations observed in men differed before and after the
      introduction of sildenafil, the first oral erectile dysfunction medication
      approved by the Food and Drug Administration. METHODS: We used Cox proportional
      hazards regression to analyze the time to first STI diagnosis in a random sample
      of married, Medicare-eligible couples aged 67 to 99 years in 1993 (N = 420 790
      couples). RESULTS: Twenty-one percent of male and 43% of female participants lost
      a spouse during the 9-year study period. Only 0.65% of men and 0.97% of women
      were diagnosed with an STI. Widowhood was associated with an increased risk of
      STI diagnosis for men only, with the largest effects found 0.5 to 1 year after a
      wife's death. Effects for men were larger after the introduction of sildenafil.
      CONCLUSIONS: Widowhood in older men, but not women, increased the risk for STIs,
      especially in the postsildenafil era. Clinicians should address sexual health
      issues with older patients, especially bereaved men taking erectile dysfunction
      medications.

PMID- 19762657
TI  - Viability of commercially available bleach for water treatment in developing
      countries.
AB  - Treating household water with low-cost, widely available commercial bleach is
      recommended by some organizations to improve water quality and reduce disease in
      developing countries. I analyzed the chlorine concentration of 32 bleaches from
      12 developing countries; the average error between advertised and measured
      concentration was 35% (range = -45%-100%; standard deviation = 40%). Because of
      disparities between advertised and actual concentration, the use of commercial
      bleach for water treatment in developing countries is not recommended without
      ongoing quality control testing.

PMID- 19762658
TI  - Water, conflict, and hope.

PMID- 19762659
TI  - Health insurance and mortality in US adults.
AB  - OBJECTIVES: A 1993 study found a 25% higher risk of death among uninsured
      compared with privately insured adults. We analyzed the relationship between
      uninsurance and death with more recent data. METHODS: We conducted a survival
      analysis with data from the Third National Health and Nutrition Examination
      Survey. We analyzed participants aged 17 to 64 years to determine whether
      uninsurance at the time of interview predicted death. RESULTS: Among all
      participants, 3.1% (95% confidence interval [CI]=2.5%, 3.7%) died. The hazard
      ratio for mortality among the uninsured compared with the insured, with
      adjustment for age and gender only, was 1.80 (95% CI=1.44, 2.26). After
      additional adjustment for race/ethnicity, income, education, self- and physician
      rated health status, body mass index, leisure exercise, smoking, and regular
      alcohol use, the uninsured were more likely to die (hazard ratio=1.40; 95%
      CI=1.06, 1.84) than those with insurance. CONCLUSIONS: Uninsurance is associated
      with mortality. The strength of that association appears similar to that from a
      study that evaluated data from the mid-1980s, despite changes in medical
      therapeutics and the demography of the uninsured since that time.

PMID- 19762660
TI  - Changes not for the fainthearted: reorienting health care systems toward health
      equity through action on the social determinants of health.
AB  - Entrenched poor health and health inequity are important public health problems.
      Conventionally, solutions to such problems originate from the health care sector,
      a conception reinforced by the dominant biomedical imagination of health. By
      contrast, attention to the social determinants of health has recently been given
      new force in the fight against health inequity. The health care sector is a vital
      determinant of health in itself and a key resource in improving health in an
      equitable manner. Actors in the health care sector must recognize and reverse the
      sector's propensity to generate health inequity. The sector must also strengthen
      its role in working with other sectors of government to act collectively on the
      deep-rooted causes of poor and inequitable health.

PMID- 19762661
TI  - Medication prescribing practices for older prisoners in the Texas prison system.
AB  - OBJECTIVES: We sought to assess appropriateness of medication prescribing for
      older Texas prisoners. METHODS: In this 12-month cross-sectional study of 13 117
      prisoners (aged > or = 55 years), we assessed medication use with Zhan criteria
      and compared our results to prior studies of community prescribing. We assessed
      use of indicated medications with 6 Assessing Care of Vulnerable Elders
      indicators. RESULTS: Inappropriate medications were prescribed to a third of
      older prisoners; half of inappropriate use was attributable to over-the-counter
      antihistamines. When these antihistamines were excluded, inappropriate use
      dropped to 14% (> or = 55 years) and 17% (> or = 65 years), equivalent to rates
      in a Department of Veterans Affairs study (17%) and lower than rates in a health
      maintenance organization study (26%). Median rate of indicated medication use for
      the 6 indicators was 80% (range = 12%-95%); gastrointestinal prophylaxis for
      patients on nonsteroidal anti-inflammatories at high risk for gastrointestinal
      bleed constituted the lowest rate. CONCLUSIONS: Medication prescribing for older
      prisoners in Texas was similar to that for older community adults. However,
      overuse of antihistamines and underuse of gastrointestinal prophylaxis suggests a
      need for education of prison health care providers in appropriate prescribing
      practices for older adults.

PMID- 19762662
TI  - Pregnancy as a window of opportunity for HIV prevention: effects of an HIV
      intervention delivered within prenatal care.
AB  - OBJECTIVES: We sought to determine whether an HIV prevention program bundled with
      group prenatal care reduced sexually transmitted infection (STI) incidence,
      repeat pregnancy, sexual risk behavior, and psychosocial risks. METHODS: We
      conducted a randomized controlled trial at 2 prenatal clinics. We assigned
      pregnant women aged 14 to 25 years (N = 1047) to individual care, attention
      matched group care, and group care with an integrated HIV component. We conducted
      structured interviews at baseline (second trimester), third trimester, and 6 and
      12 months postpartum. RESULTS: Mean age of participants was 20.4 years; 80% were
      African American. According to intent-to-treat analyses, women assigned to the
      HIV-prevention group intervention were significantly less likely to have repeat
      pregnancy at 6 months postpartum than individual-care and attention-matched
      controls; they demonstrated increased condom use and decreased unprotected sexual
      intercourse compared with individual-care and attention-matched controls.
      Subanalyses showed that being in the HIV-prevention group reduced STI incidence
      among the subgroup of adolescents. CONCLUSION: HIV prevention integrated with
      prenatal care resulted in reduced biological, behavioral, and psychosocial risks
      for HIV.

PMID- 19762663
TI  - The Sonoma water evaluation trial: a randomized drinking water intervention trial
      to reduce gastrointestinal illness in older adults.
AB  - OBJECTIVES: We estimated the relative rate of highly credible gastrointestinal
      illness (HCGI) per year associated with active versus sham household water
      filtration devices among older adults in a community receiving tap water meeting
      current US standards. METHODS: We conducted a randomized, triple-blinded,
      crossover trial in 714 households (988 individuals), which used active and sham
      water filtration devices for 6 months each. We estimated the annual incidence
      rate ratio of HCGI episodes and the longitudinal prevalence ratio of HCGI days at
      population and individual levels with a generalized estimating equation (GEE) and
      generalized linear mixed models (GLMMs), respectively, adjusted for covariates
      associated with outcome. RESULTS: The incidence rate ratios (active versus sham)
      were 0.88 (95% confidence interval [CI] = 0.77, 1.00) and 0.85 (95% CI = 0.76,
      0.94) HCGI episodes per year estimated by GEE and GLMM models, respectively. The
      corresponding longitudinal prevalence ratios were 0.88 (95% CI = 0.74, 1.05) and
      0.84 (95% CI = 0.78, 0.90) HCGI days per person per year. CONCLUSIONS: We
      observed reductions in population- and individual-level measures of HCGI
      associated with use of the active filtration device. These findings suggest the
      need for further research on the impact of drinking water on the health of
      sensitive subpopulations.

PMID- 19762664
TI  - Improving patrons' meal selections through the use of point-of-selection
      nutrition labels.
AB  - OBJECTIVES: We examined changes in meal selection by patrons of university food
      service operations when nutrition labels were provided at the point of selection.
      METHODS: We used a quasi-experimental, single-group, interrupted time-series
      design to examine daily sales before, during, and after provision of point-of
      selection nutrition labels. Piecewise linear regression was employed to examine
      changes in the average energy content of entrees and a paired t test was used to
      detect differences in sales across the periods. RESULTS: The average energy
      content of entrees purchased by patrons dropped immediately when nutrition labels
      were made available at point of selection and increased gradually when nutrition
      information was removed. There was no significant change in number of entrees
      sold or in revenues between the 2 periods. CONCLUSIONS: Use of nutrition labels
      reduced the average energy content of entrees purchased without reducing overall
      sales. These results provide support for strengthening the nutrition labeling
      policy in food-service operations.

PMID- 19762665
TI  - Recommendations from a research consultation to address intervention strategies
      for HIV/AIDS prevention focused on African Americans.
AB  - Despite substantial federal resources spent on HIV prevention, research,
      treatment, and care, as well as the availability and dissemination of evidence
      based behavioral interventions, the disparate impact of HIV on African Americans
      continues. In October 2007, 3 federal agencies convened 20 HIV/AIDS prevention
      researchers and care providers for a research consultation to focus on new
      intervention strategies and current effective intervention strategies that should
      be more widely disseminated to address the HIV/AIDS epidemic among African
      Americans. The consultants focused on 2 areas: (1) potential directions for HIV
      prevention interventions, defined to include behavioral, community, testing,
      service delivery, structural, biomedical, and other interventions; and (2)
      improved research methods and agency procedures to better support prevention
      research focused on African American communities.

PMID- 19762666
TI  - Enhancing cultural and contextual intervention strategies to reduce HIV/AIDS
      among African Americans.
AB  - I describe 4 protective strategies that African Americans employ that may
      challenge current HIV prevention efforts: (1) an adaptive duality that protects
      identity, (2) personal control influenced by external factors, (3) long
      established indirect communication patterns, and (4) a mistrust of "outsiders." I
      propose the Sexual Health Model as a conceptual framework for HIV prevention
      interventions because it incorporates established adaptive coping strategies into
      new HIV-related protective skills. The Sexual Health Model promotes
      interconnectedness, sexual ownership, and body awareness, 3 concepts that
      represent the context of the African American historical and cultural experience
      and that enhance rather than contradict future prevention efforts.

PMID- 19762667
TI  - Water pipe tobacco smoking among middle and high school students.
AB  - OBJECTIVES: We examined prevalence rates of water pipe tobacco smoking among
      young people as a first step in assessing the health implications of this form of
      tobacco use. METHODS: We examined water pipe use with data from the 2007 Florida
      Youth Tobacco Survey, which assessed tobacco-related beliefs, attitudes, and
      behaviors among the state's middle and high school students. RESULTS: Four
      percent of middle school students and 11% of high school students reported ever
      having used a water pipe. Adolescent boys were significantly more likely than
      adolescent girls to use water pipes, and African American adolescents were
      significantly less likely than adolescents from other racial/ethnic backgrounds
      to do so. Those who indicated ever having tried cigarettes and those who reported
      positive attitudes toward the social nature of cigarette use were more likely to
      have tried water pipes. CONCLUSIONS: Water pipe use appears to be widespread
      among middle and high school students. Further research is needed to assess the
      health risks associated with water pipe tobacco smoking as well as young people's
      attitudes toward this form of tobacco use.

PMID- 19762668
TI  - Impact of drainage networks on cholera outbreaks in Lusaka, Zambia.
AB  - OBJECTIVES: We investigated the association between precipitation patterns and
      cholera outbreaks and the preventative roles of drainage networks against
      outbreaks in Lusaka, Zambia. METHODS: We collected data on 6542 registered
      cholera patients in the 2003-2004 outbreak season and on 6045 cholera patients in
      the 2005-2006 season. Correlations between monthly cholera incidences and amount
      of precipitation were examined. The distribution pattern of the disease was
      analyzed by a kriging spatial analysis method. We analyzed cholera case
      distribution and spatiotemporal cluster by using 2590 cholera cases traced with a
      global positioning system in the 2005-2006 season. The association between
      drainage networks and cholera cases was analyzed with regression analysis.
      RESULTS: Increased precipitation was associated with the occurrence of cholera
      outbreaks, and insufficient drainage networks were statistically associated with
      cholera incidences. CONCLUSIONS: Insufficient coverage of drainage networks
      elevated the risk of cholera outbreaks. Integrated development is required to
      upgrade high-risk areas with sufficient infrastructure for a long-term cholera
      prevention strategy.

PMID- 19762669
TI  - Left too early: the effects of age at separation from parents on Chinese rural
      children's symptoms of anxiety and depression.
AB  - OBJECTIVES: We examined the effect of age at separation from parents on symptoms
      of anxiety and depression among children in rural communities in China whose
      parents migrated to cities in search of employment opportunities during the
      country's rapid economic development. METHODS: Students in 3 rural areas, Anhui,
      Chongqing, and Guizhou (N = 592; age = 10-17 years), completed questionnaires
      that asked about symptoms of state and trait anxiety, as well as depression and
      age at separation from parents. RESULTS: Children who were separated from parents
      at a younger age had more symptoms of anxiety and depression. This effect was
      especially pronounced for children who were separated from their mothers or from
      both parents. CONCLUSIONS: China's explosive economic growth appears to exact a
      significant toll on left-behind children's mental health, particularly on
      children whose parents left early in their lives. The unintended consequences of
      the economic boom on child development need to be further examined in prospective
      studies.

PMID- 19762670
TI  - STD prevalence, risky sexual behaviors, and sex with women in a national sample
      of Chinese men who have sex with men.
AB  - We describe the behavioral characteristics and sexually transmitted disease (STD)
      prevalence of Chinese men who have sex with men (MSM) (n = 41) from a national
      probability sample of men (n = 1861). Most MSM were partnered with females (97%)
      and had a low rate of consistent condom use (7%). More MSM than heterosexual men
      self-reported a prior STD and risky sexual behaviors. MSM may act as a bridge for
      HIV transmission to female partners. Targeted interventions may help prevent a
      generalized HIV epidemic in China.

PMID- 19762671
TI  - Stroke mortality among Alaska Native people.
AB  - OBJECTIVES: We aimed to describe the epidemiology of stroke among Alaska Natives,
      which is essential for designing effective stroke prevention and intervention
      efforts for this population. METHODS: We conducted an analysis of death
      certificate data for the state of Alaska for the period 1984 to 2003, comparing
      age-standardized stroke mortality rates among Alaska Natives residing in Alaska
      vs US Whites by age category, gender, stroke type, and time. RESULTS: Compared
      with US Whites, Alaska Natives had significantly elevated stroke mortality from
      1994 to 2003 but not from 1984 to 1993. Alaska Native women of all age groups and
      Alaska Native men younger than 45 years of age had the highest risk, although the
      rates for those younger than 65 years were statistically imprecise. Over the 20
      year study period, the stroke mortality rate was stable for Alaska Natives but
      declined for US Whites. CONCLUSIONS: Stroke mortality is higher among Alaska
      Natives, especially women, than among US Whites. Over the past 20 years, there
      has not been a significant decline in stroke mortality among Alaska Natives.

PMID- 19762672
TI  - Relationship between alcohol use and violent behavior among urban African
      American youths from adolescence to emerging adulthood: a longitudinal study.
AB  - OBJECTIVES: We examined developmental trajectories of alcohol use and violent
      behavior among urban African American youths and the longitudinal relationship
      between these behaviors from adolescence to emerging adulthood. METHODS: Our
      sample included 649 African American youths (49% male) followed for 8 years. We
      assessed violent behavior and alcohol use by asking participants how often they
      had engaged in each behavior in the preceding 12 months. Growth curve analyses
      were conducted to identify the developmental trajectories of the 2 behaviors and
      to explore the longitudinal relationship between them. RESULTS: Violent behavior
      peaked in middle to late adolescence and declined thereafter, whereas the
      frequency of alcohol use increased steadily over time. These developmental
      trajectories varied according to gender. Among both male and female participants,
      early violent behavior predicted later alcohol use, and early alcohol use
      predicted later violent behavior. Moreover, changes in one behavior were
      associated with changes in the other. CONCLUSIONS: Our results support a
      bidirectional relationship between alcohol use and violent behavior. Efforts to
      reduce one problem can be expected to reduce the other. Programs and policies
      aimed at reducing violence or alcohol use among adolescents should take into
      account this relationship.

PMID- 19762673
TI  - Social-environmental factors and protective sexual behavior among sex workers:
      the Encontros intervention in Brazil.
AB  - OBJECTIVES: We sought to determine the association of social-environmental
      factors with condom use and sexually transmitted infections (STIs) among 420 sex
      workers participating in an STI/HIV prevention study in Corumba, Brazil, to
      inform future intervention efforts. METHODS: Participants provided urine samples
      for polymerase chain reaction testing of chlamydia and gonorrhea and responded to
      multi-item scales addressing perceived social cohesion, participation in
      networks, and access to and management of resources. We conducted multivariate
      log-linear and negative binomial regression analyses of these data. RESULTS:
      Increased social cohesion was inversely associated with number of unprotected sex
      acts in the preceding week among women (adjusted incidence rate ratio [IRR] =
      0.80; P < .01), and there was a marginal association among men (adjusted IRR =
      0.41; P = .08). Women's increased participation in social networks was associated
      with a decrease in frequency of unprotected sex acts (adjusted IRR = 0.83; P =
      .04), as was men's access to and management of social and material resources (IRR
      = 0.15; P = .01). Social-environmental factors were not associated with STIs.
      CONCLUSIONS: The social context within which populations negotiate sexual
      behaviors is associated with condom use. Future efforts to prevent STI/HIV should
      incorporate strategies to modify the social environment.

PMID- 19762674
TI  - Risk assessment and screening for sexually transmitted infections, HIV, and
      hepatitis virus among long-distance truck drivers in New Mexico, 2004-2006.
AB  - OBJECTIVES: We examined sexually transmitted infection (STI), HIV, and hepatitis
      virus prevalence and risk behaviors among truck drivers. METHODS: We asked
      participants about their risk behaviors, and we screened them for STIs, HIV, and
      hepatitis infections. We used logistic regression to identify factors associated
      with outcomes. RESULTS: Of the 652 enrolled participants, 21% reported sex with
      sex workers or casual partners in the prior year. Driving solo (odds ratio [OR] =
      15.04; 95% confidence interval [CI] = 1.92, 117.53; P = .01), history of
      injection drug use (IDU; OR = 2.69; 95% CI = 1.19, 6.12; P = .02), and history of
      an STI (OR = 2.47; 95% CI = 1.19, 5.09; P = .01) were independently associated
      with high-risk sexual behaviors. Fourteen percent of participants reported drug
      use in the previous year, and 11% reported having ever injected drugs.
      Participants tested positive as follows: 54 for HCV antibodies (8.5%), 66 for
      hepatitis B anticore (anti-HBc) antibodies (10.4%), 8 for chlamydia (1.3%), 1 for
      gonorrhea (0.2%), 1 for syphilis (0.2%), and 1 for HIV (0.2%). History of
      injecting drugs (OR = 26.91; 95% CI = 11.61, 62.39; P < .01) and history of anti
      HBc antibodies (OR = 7.89; 95% CI = 3.16, 19.68; P < .01) were associated with
      HCV infection. CONCLUSIONS: Our results suggest a need for hepatitis C screening
      and STI risk-reduction interventions in this population.

PMID- 19762675
TI  - Investigating the link between gun possession and gun assault.
AB  - OBJECTIVES: We investigated the possible relationship between being shot in an
      assault and possession of a gun at the time. METHODS: We enrolled 677 case
      participants that had been shot in an assault and 684 population-based control
      participants within Philadelphia, PA, from 2003 to 2006. We adjusted odds ratios
      for confounding variables. RESULTS: After adjustment, individuals in possession
      of a gun were 4.46 (P < .05) times more likely to be shot in an assault than
      those not in possession. Among gun assaults where the victim had at least some
      chance to resist, this adjusted odds ratio increased to 5.45 (P < .05).
      CONCLUSIONS: On average, guns did not protect those who possessed them from being
      shot in an assault. Although successful defensive gun uses occur each year, the
      probability of success may be low for civilian gun users in urban areas. Such
      users should reconsider their possession of guns or, at least, understand that
      regular possession necessitates careful safety countermeasures.

PMID- 19762676
TI  - The efficacy of HIV/STI behavioral interventions for African American females in
      the United States: a meta-analysis.
AB  - OBJECTIVES: We evaluated the efficacy of HIV behavioral interventions for African
      American females in the United States, and we identified factors associated with
      intervention efficacy. METHODS: We conducted a comprehensive literature review
      covering studies published from January 1988 to June 2007, which yielded 37
      relevant studies. Data were analyzed using mixed-effects models and meta
      regression. RESULTS: Overall, behavioral interventions had a significant impact
      on reductions in HIV-risk sex behaviors (odds ratio [OR] = 0.63; 95% confidence
      interval [CI] = 0.54, 0.75; n = 11 239; Cochrane Q(32) = 84.73; P < .001) and
      sexually transmitted infections (STIs; OR = 0.81; 95% CI = 0.67, 0.98; n = 8760;
      Cochrane Q(16) = 22.77; P = .12). Greater intervention efficacy was observed in
      studies that specifically targeted African American females used gender- or
      culture-specific materials, used female deliverers, addressed empowerment issues,
      provided skills training in condom use and negotiation of safer sex, and used
      role-playing to teach negotiation skills. CONCLUSIONS: Behavioral interventions
      are efficacious at preventing HIV and STIs among African American females. More
      research is needed to examine the potential contribution of prevention strategies
      that attend to community-level and structural-level factors affecting HIV
      infection and transmission in this population.

PMID- 19762677
TI  - The Hispanic mortality advantage and ethnic misclassification on US death
      certificates.
AB  - OBJECTIVES: We tested the data artifact hypothesis regarding the Hispanic
      mortality advantage by investigating whether and to what degree this advantage is
      explained by Hispanic origin misclassification on US death certificates. METHODS:
      We used the National Longitudinal Mortality Study, which links Current Population
      Survey records to death certificates for 1979 through 1998, to estimate the
      sensitivity, specificity, and net ascertainment of Hispanic ethnicity on death
      certificates compared with survey classifications. Using national vital
      statistics mortality data, we estimated Hispanic age-specific and age-adjusted
      death rates, which were uncorrected and corrected for death certificate
      misclassification, and produced death rate ratios comparing the Hispanic with the
      non-Hispanic White population. RESULTS: Hispanic origin reporting on death
      certificates in the United States is reasonably good. The net ascertainment of
      Hispanic origin is just 5% higher on survey records than on death certificates.
      Corrected age-adjusted death rates for Hispanics are lower than those for the non
      Hispanic White population by close to 20%. CONCLUSIONS: The Hispanic mortality
      paradox is not explained by an incongruence between ethnic classification in
      vital registration and population data systems.

PMID- 19762678
TI  - Universal intervention as a protective shield against exposure to substance use:
      long-term outcomes and public health significance.
AB  - OBJECTIVES: We examined universal preventive intervention effects on adolescents'
      exposure to opportunities for substance use and on illicit substance use in the
      long term. METHODS: Public schools (N = 22) were randomly assigned to the Iowa
      Strengthening Families Program (ISFP) or a control condition. We used odds ratio
      (OR) calculations and structural modeling to test the effects of the ISFP in the
      6th grade on exposure to substance use across adolescence, as well as on 12th
      grade illicit substance use occurring via reductions in exposure. RESULTS: The
      ISFP was associated with reduced exposure to illicit substance use (1.25 < or =
      OR < or = 2.37) that was, in turn, associated with reduced 12th-grade substance
      use (2.87 < or = OR < or = 6.35). The ISFP also reduced the rate of increase in
      exposure across adolescence (B = -0.37; P < .001), which was associated with the
      likelihood of 12th-grade illicit substance use (B = 0.30; P = .021), with a
      significant indirect effect (B = -0.11; P = .048). CONCLUSIONS: The ISFP in the
      6th grade reduced substance use through a "protective shield" of reduced
      exposure. The relative reduction rate was 49%, which suggests that universal
      prevention shields can contribute to significant reductions in illicit substance
      use among adolescents.

PMID- 19762679
TI  - Ultrastructural and functional remodeling of the coupling between Ca2+ influx and
      sarcoplasmic reticulum Ca2+ release in right atrial myocytes from experimental
      persistent atrial fibrillation.
AB  - RATIONALE: Persistent atrial fibrillation (AF) has been associated with
      structural and electric remodeling and reduced contractile function. OBJECTIVE:
      To unravel mechanisms underlying reduced sarcoplasmic reticulum (SR) Ca(2+)
      release in persistent AF. METHODS: We studied cell shortening, membrane currents,
      and [Ca(2+)](i) in right atrial myocytes isolated from sheep with persistent AF
      (duration 129+/-39 days, N=16), compared to matched control animals (N=21). T
      tubule density, ryanodine receptor (RyR) distribution, and local [Ca(2+)](i)
      transients were examined in confocal imaging. RESULTS: Myocyte shortening and
      underlying [Ca(2+)](i) transients were profoundly reduced in AF (by 54.8% and
      62%, P<0.01). This reduced cell shortening could be corrected by increasing
      [Ca(2+)](i). SR Ca(2+) content was not different. Calculated fractional SR Ca(2+)
      release was reduced in AF (by 20.6%, P<0.05). Peak Ca(2+) current density was
      modestly decreased (by 23.9%, P<0.01). T-tubules were present in the control
      atrial myocytes at low density and strongly reduced in AF (by 45%, P<0.01),
      whereas the regular distribution of RyR was unchanged. Synchrony of SR Ca(2+)
      release in AF was significantly reduced with increased areas of delayed Ca(2+)
      release. Propagation between RyR was unaffected but Ca(2+) release at
      subsarcolemmal sites was reduced. Rate of Ca(2+) extrusion by Na(+)/Ca(2+)
      exchanger was increased. CONCLUSIONS: In persistent AF, reduced SR Ca(2+) release
      despite preserved SR Ca(2+) content is a major factor in contractile dysfunction.
      Fewer Ca(2+) channel-RyR couplings and reduced efficiency of the coupling at
      subsarcolemmal sites, possibly related to increased Na(+)/Ca(2+) exchanger,
      underlie the reduction in Ca(2+) release.

PMID- 19762680
TI  - Shear stress regulates angiotensin type 1 receptor expression in endothelial
      cells.
AB  - RATIONALE: Shear stress (SS) has an established role in atherosclerotic plaque
      localization, but how it exerts its protective effect is not fully understood.
      OBJECTIVE: To test the hypothesis that SS may downregulate angiotensin type 1
      receptors (AT(1)Rs). Angiotensin II has been shown to be proinflammatory and to
      promote atherosclerosis. METHODS AND RESULTS: Using immunohistochemistry, we
      found a pronounced expression of AT(1)R in the inner, atheroprone regions of the
      aortic arch of C57BL/6 and endothelial NO synthase-deficient (eNOS(-/-)) mice but
      not eNOS-overexpressing mice. In human umbilical vein endothelial cells (HUVECs),
      laminar SS (15 dyn/cm(2)) induced a biphasic decrease in AT(1)R protein
      expression characterized by a first reduction at 1 hour (31+/-4% of static
      control, P<0.01), partial recovery at 3 hours (65+/-9%), and a second more
      prolonged decline at 6, 12, and 24 hours (48+/-9%, 36+/-9%, 33+/-5%,
      respectively, P<0.05). One and 24 hours of SS significantly reduced fluorescent
      angiotensin binding compared to static HUVECs. Shear-induced downregulation of
      AT(1)R was abolished by treatment with protein kinase A and G inhibitors or N(G)
      nitro-l-arginine methyl ester (L-NAME). Fittingly, stimulating static HUVECs with
      an NO donor decreased AT(1)R protein levels. RT-PCR revealed a significant
      (P<0.05) decrease of AT(1)R mRNA in HUVECs exposed to SS during 3 (6+/-2% of
      static control), 6 (4+/-1%), 12 (4+/-1%), and 24 hours (15+/-4%), suggesting a
      transcriptional downregulation of AT(1)R at length. Finally, angiotensin-induced
      vascular cell adhesion molecule was abated in HUVECs exposed to SS and in the
      outer aortic arch of mice. CONCLUSIONS: Our results demonstrate that SS may
      convey some of its atheroprotective effects through downregulation of AT(1)R in
      endothelial cells.

PMID- 19762681
TI  - Myeloid differentiation factor-88/interleukin-1 signaling controls cardiac
      fibrosis and heart failure progression in inflammatory dilated cardiomyopathy.
AB  - RATIONALE: The myeloid differentiation factor (MyD)88/interleukin (IL)-1 axis
      activates self-antigen-presenting cells and promotes autoreactive CD4(+) T-cell
      expansion in experimental autoimmune myocarditis, a mouse model of inflammatory
      heart disease. OBJECTIVE: The aim of this study was to determine the role of
      MyD88 and IL-1 in the progression of acute myocarditis to an end-stage heart
      failure. METHODS AND RESULTS: Using alpha-myosin heavy chain peptide (MyHC-alpha)
      loaded, activated dendritic cells, we induced myocarditis in wild-type and MyD88(
      /-) mice with similar distributions of heart-infiltrating cell subsets and
      comparable CD4(+) T-cell responses. Injection of complete Freund's adjuvant (CFA)
      or MyHC-alpha/CFA into diseased mice promoted cardiac fibrosis, induced
      ventricular dilation, and impaired heart function in wild-type but not in MyD88(
      /-) mice. Experiments with chimeric mice confirmed the bone marrow origin of the
      fibroblasts replacing inflammatory infiltrates and showed that MyD88 and IL-1
      receptor type I signaling on bone marrow-derived cells was critical for
      development of cardiac fibrosis during progression to heart failure. CONCLUSIONS:
      Our findings indicate a critical role of MyD88/IL-1 signaling in the bone marrow
      compartment in postinflammatory cardiac fibrosis and heart failure and point to
      novel therapeutic strategies against inflammatory cardiomyopathy.

PMID- 19762682
TI  - Periadventitial adipose tissue plays a critical role in vascular remodeling.
AB  - RATIONALE: Obesity is associated with a high incidence of cardiovascular
      complications. However, the molecular link between obesity and vascular disease
      is not fully understood. Most previous studies have focused on the association
      between cardiovascular disease and accumulation of visceral fat. Periadventitial
      fat is distributed ubiquitously around arteries throughout the body. OBJECTIVE:
      Here, we investigated the impact of obesity on inflammation in the
      periadventitial adipose tissue and on lesion formation after vascular injury.
      METHODS AND RESULTS: High-fat, high-sucrose feeding induced inflammatory changes
      and decreased adiponectin expression in the periadventitial adipose tissue, which
      was associated with enhanced neointima formation after endovascular injury.
      Removal of periadventitial fat markedly enhanced neointima formation after
      injury, which was attenuated by transplantation of subcutaneous adipose tissue
      from mice fed on regular chow. Adiponectin-deficient mice showed markedly
      enhanced lesion formation, which was reversed by local delivery, but not systemic
      administration, of recombinant adiponectin to the periadventitial area. The
      conditioned medium from subcutaneous fat attenuated increased cell number of
      smooth muscle cells in response to platelet derived growth factor-BB.
      CONCLUSIONS: Our findings suggest that periadventitial fat may protect against
      neointimal formation after angioplasty under physiological conditions and that
      inflammatory changes in the periadventitial fat may have a direct role in the
      pathogenesis of vascular disease accelerated by obesity.

PMID- 19762683
TI  - Concurrent vasculogenesis and neurogenesis from adult neural stem cells.
AB  - RATIONALE: Recent reports have demonstrated that signals from vascular
      endothelial cells are necessary for organogenesis that may precede
      vasculogenesis. However, the origin of these neovascular cells in regenerating
      tissue has not been clarified. OBJECTIVE: Here we tested the hypothesis that
      adult neural stem cells (NSCs) can differentiate into vascular lineage, as well
      as neural lineage, in the process of collaborative organogenesis. METHODS AND
      RESULTS: NSCs, clonally isolated from mouse brain, were shown to develop
      endothelial and smooth muscle phenotypes in vitro. To elucidate whether NSCs can
      simultaneously differentiate into vascular and neural cells in vivo, genetically
      labeled NSCs were administered to mice with unilateral sciatic nerve crush injury
      or operatively induced brain and myocardial ischemia. Two weeks later, necropsy
      examination disclosed recruitment of the labeled NSCs to sites of injury
      differentiating into vascular cells (endothelial cells and vascular smooth muscle
      cells) and Schwann cells in regenerating nerve. Similarly, NSC-derived vascular
      cells/astrocytes and endothelial cells were identified in ischemic brain tissue
      and capillaries in myocardium 2 weeks following transplantation, respectively.
      CONCLUSIONS: These findings, concurrent vasculogenesis and neurogenesis from a
      common stem cell, suggest that certain somatic stem cells are capable of
      differentiating into not only somatic cells of identity but also into vascular
      cells for tissue regeneration.

PMID- 19762684
TI  - Insulin-like growth factor binding protein-3 mediates vascular repair by
      enhancing nitric oxide generation.
AB  - RATIONALE: Insulin-like growth factor binding protein (IGFBP)-3 modulates
      vascular development by regulating endothelial progenitor cell (EPC) behavior,
      specifically stimulating EPC cell migration. This study was undertaken to
      investigate the mechanism of IGFBP-3 effects on EPC function and how IGFBP-3
      mediates cytoprotection following vascular injury. OBJECTIVE: To examine the
      mechanism of IGFBP-3-mediated repair following vascular injury. METHODS AND
      RESULTS: We used 2 complementary vascular injury models: laser occlusion of
      retinal vessels in adult green fluorescent protein (GFP) chimeric mice and oxygen
      induced retinopathy in mouse pups. Intravitreal injection of IGFBP-3-expressing
      plasmid into lasered GFP chimeric mice stimulated homing of EPCs, whereas
      reversing ischemia induced increases in macrophage infiltration. IGFBP-3 also
      reduced the retinal ceramide/sphingomyelin ratio that was increased following
      laser injury. In the OIR model, IGFBP-3 prevented cell death of resident vascular
      endothelial cells and EPCs, while simultaneously increasing astrocytic
      ensheathment of vessels. For EPCs to orchestrate repair, these cells must migrate
      into ischemic tissue. This migratory ability is mediated, in part, by endogenous
      NO generation. Thus, we asked whether the migratory effects of IGFBP-3 were
      attributable to stimulation of NO generation. IGFBP-3 increased endothelial NO
      synthase expression in human EPCs leading to NO generation. IGFBP-3 exposure also
      led to the redistribution of vasodilator-stimulated phosphoprotein, an NO
      regulated protein critical for cell migration. IGFBP-3-mediated NO generation
      required high-density lipoprotein receptor activation and stimulation of
      phosphatidylinositol 3-kinase/Akt pathway. CONCLUSION: These studies support
      consideration of IGFBP-3 as a novel agent to restore the function of injured
      vasculature and restore NO generation.

PMID- 19762685
TI  - Transcriptional upregulation of mitochondrial uncoupling protein 2 protects
      against oxidative stress-associated neurogenic hypertension.
AB  - RATIONALE: Mitochondrial uncoupling proteins (UCPs) belong to a superfamily of
      mitochondrial anion transporters that uncouple ATP synthesis from oxidative
      phosphorylation and mitigates mitochondrial reactive oxygen species production.
      OBJECTIVE: We assessed the hypothesis that UCP2 participates in central
      cardiovascular regulation by maintaining reactive oxygen species homeostasis in
      the rostral ventrolateral medulla (RVLM), where sympathetic premotor neurons that
      maintain vasomotor tone located. We also elucidated the molecular mechanisms that
      underlie transcriptional upregulation of UCP2 in response to oxidative stress in
      RVLM. METHODS AND RESULTS: In Sprague-Dawley rats, transcriptional upregulation
      of UCP2 in RVLM by rosiglitazone, an activator of its transcription factor
      peroxisome proliferator-activated receptor (PPAR)gamma, reduced mitochondrial
      hydrogen peroxide level in RVLM and systemic arterial pressure. Oxidative stress
      induced by microinjection of angiotensin II into RVLM augmented UCP2 mRNA or
      protein expression in RVLM, which was antagonized by comicroinjection of NADPH
      oxidase inhibitor (diphenyleneiodonium chloride), superoxide dismutase mimetic
      (tempol), or p38 mitogen-activated protein kinase inhibitor (SB203580) but not by
      extracellular signal-regulated kinase 1/2 inhibitor (U0126). Angiotensin II also
      induced phosphorylation of the PPARgamma coactivator, PPARgamma coactivator (PGC)
      1alpha, and an increase in formation of PGC-1alpha/PPARgamma complexes in a p38
      mitogen-activated protein kinase-dependent manner. Intracerebroventricular
      infusion of angiotensin II promoted an increase in mitochondrial hydrogen
      peroxide production in RVLM and chronic pressor response, which was potentiated
      by gene knockdown of UCP2 but blunted by rosiglitazone. CONCLUSIONS: These
      results suggest that transcriptional upregulation of mitochondrial UCP2 in
      response to an elevation in superoxide plays an active role in feedback
      regulation of reactive oxygen species production in RVLM and neurogenic
      hypertension associated with chronic oxidative stress.

PMID- 19762686
TI  - Aldosterone-induced activation of signaling pathways requires activity of
      angiotensin type 1a receptors.
AB  - RATIONALE: Aldosterone has been shown to induce vascular damage, endothelial
      dysfunction, and myocardial fibrosis, which depend in part on activation of
      angiotensin II (Ang II)-mediated pathways. However, mechanisms underlying
      crosstalk between Ang II type 1 receptor (AT(1)R) and mineralocorticoid receptor
      (MR) are mostly unknown. OBJECTIVES: We tested whether the lack of Ang II type 1a
      receptor (AT(1a)R) or Ang II type 1b receptor (AT(1b)R) would decrease cellular
      effects induced by aldosterone. METHODS AND RESULTS: We examined the effect of
      Ang II or aldosterone after transfection of mesenteric vascular smooth muscle
      cells (VSMCs) from C57Bl/6 mice with small interference RNA for AT(1a)R, AT(1b)R,
      or MR for 48 hours. Ang II and aldosterone separately induced ERK1/2, c-Jun NH2
      terminal protein kinase (JNK), and nuclear factor (NF)-kappaB phosphorylation
      after a 20-minute stimulation. Small interference RNA for AT(1a)R downregulated
      phosphorylation of ERK1/2, JNK, and NF-kappaB after aldosterone stimulation
      compared to controls. Downregulation of AT(1b)R or MR only abolished the
      activation of NF-kappaB. In VSMCs from C57Bl/6 mice, aldosterone and Ang II
      induced the activation of the c-fos promoter from 30 minutes to 1 hour. This
      effect was blocked when using VSMCs from AT(1a)R knockout mice. CONCLUSION: We
      show for the first time that nongenomic and genomic effects of aldosterone are
      differentially dependent on activity of both AT(1a)R and AT(1b)R. Our data
      suggest that aldosterone augments AT(1)R-dependent activation of ERK1/2, JNK, and
      NF-kappaB in VSMCs. We provide mechanistic understanding and experimental in
      vitro support for the benefit of combination therapy with dual blockade of AT(1)R
      and MR to treat hypertension and progression of heart failure as reported in
      clinical studies and animal models.

PMID- 19762687
TI  - Imaging data reveal a higher pediatric stroke incidence than prior US estimates.
AB  - BACKGROUND AND PURPOSE: Prior annualized estimates of pediatric ischemic stroke
      incidence have ranged from 0.54 to 1.2 per 100,000 US children but relied purely
      on diagnostic code searches to identify cases. We sought to obtain a new estimate
      using both diagnostic code searches and searches of radiology reports and to
      assess the relative value of these 2 strategies. METHODS: Using the population of
      2.3 million children (<20 years old) enrolled in a Northern Californian managed
      care plan (1993 to 2003), we performed electronic searches of (1) inpatient and
      outpatient diagnoses for International Classification of Diseases, 9th Revision
      codes suggestive of stroke and cerebral palsy; and (2) radiology reports for key
      words suggestive of infarction. Cases were confirmed through chart review. We
      calculated sensitivities and positive predictive values for the 2 search
      strategies. RESULTS: We identified 1307 potential cases from the International
      Classification of Diseases, 9th Revision code search and 510 from the radiology
      search. A total of 205 ischemic stroke cases were confirmed, yielding an ischemic
      stroke incidence of 2.4 per 100,000 person-years. The radiology search had a
      higher sensitivity (83%) than the International Classification of Diseases, 9th
      Revision code search (39%), although both had low positive predictive values. For
      perinatal stroke, the sensitivity of the stroke International Classification of
      Diseases, 9th Revision codes alone was 12% versus 57% for stroke and cerebral
      palsy codes combined; the radiology search was again the most sensitive (87%).
      CONCLUSIONS: Our incidence estimate doubles that of prior US reports, a
      difference at least partially explained by our use of radiology searches for case
      identification. Studies relying purely on International Classification of
      Diseases, 9th Revision code searches may underestimate childhood ischemic stroke
      rates, particularly for neonates.

PMID- 19762688
TI  - Anxiety after cardiac arrest/cardiopulmonary resuscitation: exacerbated by stress
      and prevented by minocycline.
AB  - BACKGROUND AND PURPOSE: Stress is an important risk factor for cardiovascular
      disease; however, most of the research on this topic has focused on incidence
      rather than outcome. The goal of this study was to determine the effects of prior
      exposure to chronic stress on ischemia-induced neuronal death, microglial
      activation, and anxiety-like behavior. METHODS: In Experiment 1, mice were
      exposed to 3 weeks of daily restraint (3 hours) and then subjected to either 8
      minutes of cardiac arrest/cardiopulmonary resuscitation (CA/CPR) or sham surgery.
      Anxiety-like behavior, microglial activation, and neuronal damage were assessed
      on postischemic Day 4. In Experiment 2, mice were infused
      intracerebroventricularly with minocycline (10 microg/day) to determine the
      effect of inhibiting post-CA/CPR microglial activation on the development of
      anxiety-like behavior and neuronal death. RESULTS: CA/CPR precipitated anxiety
      like behavior and increased microglial activation and neuronal damage within the
      hippocampus relative to sham surgery. Prior exposure to stress exacerbated these
      measures among CA/CPR mice, but had no significant effect on sham-operated mice.
      Treatment with minocycline reduced both neuronal damage and anxiety-like behavior
      among CA/CPR animals. Anxiety-like behavior was significantly correlated with
      measures of microglial activation but not neuronal damage. CONCLUSIONS: A history
      of stress exposure increases the pathophysiological response to ischemia and
      anxiety-like behavior, whereas inhibiting microglial activation reduces neuronal
      damage and mitigates the development of anxiety-like behavior after CA/CPR. Thus,
      modulating inflammatory signaling after cerebral ischemia may be beneficial in
      protecting the brain and preventing the development of affective disorders.

PMID- 19762689
TI  - Pre-tissue plasminogen activator blood pressure levels and risk of symptomatic
      intracerebral hemorrhage.
AB  - BACKGROUND AND PURPOSE: From small pilot studies, uncontrolled pretreatment
      systolic blood pressure >185 mm Hg and diastolic blood pressure >110 mm Hg in
      patients with acute ischemic stroke were introduced in the National Institute of
      Neurological Diseases and Stroke rtPA Stroke Study as a contraindication for
      thrombolysis. We sought to determine if pretreatment blood pressure protocol
      violations in patients with acute ischemic stroke receiving intravenous tissue
      plasminogen activator are related to the subsequent risk of symptomatic
      intracranial hemorrhage (sICH). METHODS: We reviewed medical records of
      consecutive ischemic stroke admissions treated with intravenous thrombolysis over
      a 10-year period at our tertiary care hospital. The National Institutes of Health
      Stroke Scale score on admission was used to determine baseline stroke severity.
      The closest documented blood pressure values to the time of tissue plasminogen
      activator bolus (range, 0 to 10 minutes) were considered as pretreatment blood
      pressure. Pretreatment blood pressure protocol violations were identified as
      systolic blood pressure >185 or diastolic blood pressure >110 mm Hg prebolus.
      sICH was defined as brain imaging evidence of intracranial hemorrhage with
      clinical worsening by the National Institutes of Health Stroke Scale score
      increase of >or=4 points. RESULTS: Among 510 patients with ischemic stroke
      treated with intravenous tissue plasminogen activator (282 men; mean age, 65+/-15
      years), sICH occurred in 31 patients (6.1%). Blood pressure protocol violations
      were present in 63 patients (12.4%) and they were more frequent in patients with
      sICH (26% versus 12%; P=0.019). After adjusting for demographic characteristics,
      onset-to-treatment time, baseline National Institutes of Health Stroke Scale,
      stroke risk factors and medications, pretreatment blood pressure protocol
      violations were independently associated with a higher likelihood of sICH (OR,
      2.59; 95% CI, 1.07 to 6.25; P=0.034). CONCLUSIONS: These data support current
      guidelines advising not to use intravenous tissue plasminogen activator when
      pretreatment blood pressure exceeds the prespecified thresholds by showing that
      blood pressure protocol violations are independently associated with a higher
      likelihood of sICH.

PMID- 19762690
TI  - Electrical stimulation of the cerebral cortex exerts antiapoptotic, angiogenic,
      and anti-inflammatory effects in ischemic stroke rats through phosphoinositide 3
      kinase/Akt signaling pathway.
AB  - BACKGROUND AND PURPOSE: Neuroprotective effects of electric stimulation have been
      recently shown in ischemic stroke, but the underlying mechanisms remain poorly
      understood. METHODS: Adult Wistar rats weighing 200 to 250 g received occlusion
      of the right middle cerebral artery for 90 minutes. At 1 hour after reperfusion,
      electrodes were implanted to rats on the right frontal epidural space. Electric
      stimulation, at preset current (0 to 200 microA) and frequency (0 to 50 Hz), was
      performed for 1 week. Stroke animals were subjected to behavioral tests at 3 days
      and 1 week postmiddle cerebral artery and then immediately euthanized for protein
      and immunohistochemical assays. After demonstration of behavioral and
      histological benefits, subsequent experiments pursued the mechanistic hypothesis
      that electric stimulation exerted antiapoptotic effects through the
      phosphoinositide 3-kinase-dependent pathway; thus, cortical stimulation was
      performed in the presence or absence of specific inhibitors of phosphoinositide 3
      kinase (LY294002) in stroke rats. RESULTS: Cortical stimulation abrogated the
      ischemia-associated increase in apoptotic cells in the injured cortex by
      activating antiapoptotic cascades, which was reversed by the phosphoinositide 3
      kinase inhibitor LY294002 as reflected behaviorally and immunohistochemically.
      Furthermore, brain levels of neurotrophic factors (glial cell line-derived
      neurotrophic factor, brain-derived neurotrophic factor, vascular endothelial
      growth factor) were upregulated, which coincided with enhanced angiogenesis and
      suppressed proliferation of inflammatory cells in the ischemic cortex.
      CONCLUSIONS: These results suggest that electric stimulation prevents apoptosis
      through the phosphoinositide 3-kinase pathway. Consequently, the ischemic brain
      might have been rendered as a nurturing microenvironment characterized by robust
      angiogenesis and diminished microglial/astrocytic proliferation, resulting in the
      reduction of infarct volumes and behavioral recovery. Electric stimulation is a
      novel and potent therapeutic tool for cerebral ischemia.

PMID- 19762691
TI  - Normobaric hyperoxia treatment in acute ischemic stroke.

PMID- 19762692
TI  - Hypoplasia or occlusion of the ipsilateral cranial venous drainage is associated
      with early fatal edema of middle cerebral artery infarction.
AB  - BACKGROUND AND PURPOSE: Thrombosis of the cerebral venous sinus may cause venous
      congestion, cerebral edema, and infarction. The role of cerebrovenous disorders
      in arterial ischemic stroke is unknown. The objective of this study was to
      examine the contribution of ipsilateral cranial venous abnormalities to the
      development of cerebral edema in middle cerebral artery infarction. METHODS: This
      is a retrospective study of consecutive patients with large middle cerebral
      artery infarction admitted to our neurocritical care unit from January 2007 to
      October 2008. Medical records, laboratory data, and imaging of cerebral edema and
      cranial venous sinuses were analyzed. RESULTS: Of the 14 patients identified to
      have large middle cerebral artery infarction and images of cranial venous
      drainages, 5 (35.7%) had fatal edema with clinical signs of transtentorial
      herniation. Four of the 5 patients developed fatal edema within 48 hours of ictus
      and were found to have abnormal ipsilateral cranial venous drainage, including
      atresia of the transverse sinus (one), occlusion of the internal jugular vein
      (one), and hypoplasia of the transverse sinus and internal jugular vein (2). The
      fifth patient had symmetrical bilateral cranial venous drainages and fatal edema
      at Day 5. Of the 9 patients with nonmalignant middle cerebral artery infarction,
      all had ipsilateral dominant or symmetrical bilateral venous drainages.
      CONCLUSIONS: In this small case series, we demonstrated that only the patients
      with hypoplasia or occlusion of the ipsilateral cranial venous drainage developed
      early fatal edema after large middle cerebral artery infarction. Our results
      suggest a role of cranial venous outflow abnormalities in the development of
      brain edema after arterial ischemic stroke.

PMID- 19762693
TI  - How to improve the quality of a clinical trial on traditional Chinese medicine
      for stroke.

PMID- 19762694
TI  - Routine use of intravenous low-dose recombinant tissue plasminogen activator in
      Japanese patients: general outcomes and prognostic factors from the SAMURAI
      register.
AB  - BACKGROUND AND PURPOSE: A retrospective, multicenter, observational study was
      conducted to document clinical outcomes and to identify outcome predictors in
      patients treated with low-dose intravenous recombinant tissue plasminogen
      activator (0.6 mg/kg alteplase), which was approved in Japan in 2005, within 3
      hours of stroke onset. METHODS: Consecutive patients with stroke treated with
      recombinant tissue plasminogen activator in 10 Japanese stroke centers were
      included. RESULTS: A total of 600 patients (377 men, 72+/-12 years old) were
      studied. Median National Institutes of Health Stroke Scale scores decreased from
      13 before recombinant tissue plasminogen activator to 8 at 24 hours later.
      Symptomatic intracerebral hemorrhage within 36 hours with a >or=1-point increase
      from the baseline National Institutes of Health Stroke Scale score developed in
      23 patients (3.8%; 95% CI, 2.6% to 5.7%). At 3 months, 43 patients had died
      (7.2%; 5.4% to 9.5%), and 199 patients (33.2%; 29.5% to 37.0%) had a modified
      Rankin Scale score <or=1. Analysis of 399 patients with a premorbid modified
      Rankin Scale score <or=1 who met the criteria of the European license (<or=80
      years old, an initial National Institutes of Health Stroke Scale score <or=24,
      etc) showed that 40.6% (35.9% to 45.5%) had a 3-month modified Rankin Scale score
      <or=1. After multivariate adjustment, younger age, lower initial National
      Institutes of Health Stroke Scale score, absence of internal carotid artery
      occlusion, higher Alberta Stroke Program Early CT Score on CT, and absence of
      intravenous antihypertensives just before recombinant tissue plasminogen
      activator were independently related to a 3-month modified Rankin Scale score
      <or=1. Congestive heart failure and hyperglycemia were independently related to
      mortality. CONCLUSIONS: Three-month outcomes of patients receiving low-dose
      intravenous recombinant tissue plasminogen activator therapy in the present study
      were similar to those from postmarketing surveys using 0.9 mg/kg alteplase.

PMID- 19762695
TI  - Cerebral microbleeds are frequent in infective endocarditis: a case-control
      study.
AB  - BACKGROUND AND PURPOSE: Cerebral microbleeds (CMBs) have been described using MRI
      in patients with cardiovascular risk factors or prior stroke and could be an
      indicator of small vessel disease. CMBs have been reported in isolated cases of
      infective endocarditis (IE), but their frequency and the association of CMBs with
      IE have not yet been studied. METHODS: A case-control imaging study in a referral
      institutional tertiary care center was conducted. Systematic brain MRIs,
      including T2*-weighted sequences, were performed in 60 patients with IE within 7
      days of hospital admission and in 120 age- and gender-matched control subjects
      without IE. Two neuroradiologists, who were blinded to patient characteristics,
      independently assessed the presence, location, and size of CMBs using a
      standardized form. RESULTS: The interobserver agreement level on the presence of
      CMBs was high with a kappa coefficient range (95% CI) of 0.70 (0.42 to 0.98) for
      subcortical regions to 0.91 (0.82 to 0.99) for cortical areas. CMBs were more
      prevalent in patients with IE (57% [n=34]) than in control subjects (15% [n=18];
      matched OR, 10.06; 95% CI, 3.88 to 26.07). Moreover, the OR of IE increased
      gradually with CMBs number with an OR of 6.12 (95% CI, 2.09 to 17.94) for one to
      3 CMBs and of 20.12 (95% CI, 5.20 to 77.80) for >3 CMBs. CONCLUSIONS: CMBs are
      highly frequent in patients with IE. The strong association found between IE and
      CMBs supports the need for further evaluation of CMBs as additional diagnostic
      criteria of IE.

PMID- 19762696
TI  - Pharmacogenetics and stroke.
AB  - Genetic variations have been shown to influence drug metabolism, risk of adverse
      drug events, and pharmacodynamic responses for many drugs routinely used to treat
      patients with stroke or at risk for stroke. Examples include clopidogrel,
      statins, antihypertensive medications, and coumadin. Further validation studies
      are needed to assess the clinical utility of selecting drugs and doses based on
      genetic tests. Physicians, pharmaceutical companies, regulatory agencies, and
      health insurers continue to grapple with how best to translate this burgeoning
      field into effective individualized medicine.

PMID- 19762697
TI  - Value of central event adjudication.

PMID- 19762698
TI  - Multi-modal reperfusion therapy for patients with acute anterior circulation
      stroke in Israel.
AB  - BACKGROUND AND PURPOSE: We aimed to delineate prognostic variables in Israeli
      patients with anterior circulation strokes treated with endovascular multi-modal
      reperfusion therapy (MMRT). METHODS: Clinical and radiological data from
      consecutive tpa-ineligible stroke patients with large anterior circulation
      infarcts involving either the entire internal carotid artery or the proximal
      middle cerebral artery territory were analyzed. Stroke subtypes were categorized
      according to TOAST criteria. Neurological deficits were assessed with the NIH
      stroke scale (NIHSS), and vessel recanalization was determined using the
      thrombolysis in myocardial infarction (TIMI) scale at the end of MRRT. Good
      outcome was defined as a modified Rankin score (mRS) <or=2. RESULTS: Fifty
      patients were included with a median age of 68. Thirteen patients died and 17
      patients achieved an mRS <or=2 at 90 days. Variables associated with survival on
      multivariate analysis were admission NIHSS <20 (OR 15 95% CI 1 to 230) and
      postprocedure TIMI score 2 to 3 (OR 35.5 95% CI 2.3 to 603.9). Variables
      associated with good outcome included admission NIHSS <20 (OR 9.4 95% CI 1.3 to
      71.3), day 1 NIHSS <15 (OR 6.4 95% CI 1.1 to 38.4), and postprocedure TIMI 3 (OR
      7.4 95% CI 1.1 to 50.3). CONCLUSIONS: MMRT resulted in high survival and good
      outcome rates in these critically ill patients. Lower baseline impairment and
      vessel recanalization increase the chances for good outcome. Our results suggest
      that the benefits of MMRT may merit further study and could be generalized to
      centers outside the United States and Europe.

PMID- 19762699
TI  - Severity of hypoperfusion in distinct brain regions predicts severity of
      hemispatial neglect in different reference frames.
AB  - BACKGROUND AND PURPOSE: Hemispatial neglect is among the most common and
      disabling consequences of right hemisphere stroke. A variety of variables have
      been associated with the presence or severity of neglect but have not evaluated
      the independent effects of location, severity, and volume of ischemia. Few have
      determined areas involved in different types of neglect. We identified the
      contributions of these variables to severity of viewer-centered versus stimulus
      centered neglect in acute ischemic right hemisphere stroke. METHODS: We studied
      137 patients within 24 hours of stroke onset with MR diffusion- and perfusion
      weighted imaging and a test of hemispatial neglect that distinguishes between
      viewer-centered and stimulus-centered neglect. Using multivariable linear
      regression, we identified the independent contributions of severity of ischemia
      in specific locations, volume of ischemia, and age in accounting for severity of
      each neglect type. RESULTS: Severity of hypoperfusion in angular gyrus was the
      only variable that significantly and independently contributed to severity of
      viewer-centered neglect. Volume of dysfunctional tissue and hypoperfusion in
      posterior frontal cortex also accounted for some variability in severity of
      viewer-centered neglect. Severity of hypoperfusion of superior temporal cortex
      was the only variable that independently and significantly contributed to
      severity of stimulus-centered neglect. CONCLUSIONS: Location, severity, and
      volume of ischemia together determine the type and severity of neglect after
      right hemisphere stroke. Results also show that perfusion-weighted MRI can be
      used as a semiquantitative measure of tissue dysfunction in acute stroke and can
      account for a substantial proportion of the variability in functional deficits in
      the acute stage.

PMID- 19762700
TI  - Sonic hedgehog regulates ischemia/hypoxia-induced neural progenitor
      proliferation.
AB  - BACKGROUND AND PURPOSE: Sonic hedgehog (Shh) protein is required for the
      maintenance of neural progenitor cells (NPCs) in the embryonic and adult
      hippocampus. Brain ischemia causes increased proliferation of hippocampal NPCs.
      We therefore examined whether Shh regulates the increase in proliferation of NPCs
      after ischemia/hypoxia. METHODS: Male SV129 mice were exposed to a 20-minute
      middle cerebral artery occlusion; hippocampi were then analyzed for Shh mRNA and
      protein expression by real-time polymerase chain reaction, immunoblot, and
      immunohistochemistry. Primary cell cultures of neurons, astrocytes, and NPCs were
      exposed to 16 hours of hypoxia (1% O(2)) and analyzed by real-time polymerase
      chain reaction and immunoblot for Shh expression. Proliferation of NPCs, in vivo
      and in vitro, was measured by bromodeoxyuridine incorporation. RESULTS: Among the
      cell types examined in vitro, only NPC and neurons increased Shh mRNA under
      hypoxic conditions. Furthermore, hypoxia increased proliferation of NPCs and this
      proliferation was enhanced by the addition of recombinant Shh or blocked by the
      pathway-specific inhibitor, cyclopamine. Middle cerebral artery occlusion was
      associated with a transient 2-fold increase in the mRNA encoding both Shh and its
      transcription factor, Gli1, 0.5 days after ischemia. Within the hippocampus, Shh
      protein was increased approximately 3-fold 3 and 7 days after ischemia and was
      observed predominantly within cells in the CA3 and hilar regions. Shh was
      expressed only in mature neurons. In vivo, cyclopamine suppressed ischemia
      induced proliferation of subgranular NPCs. CONCLUSIONS: The Shh pathway plays a
      role in the proliferation of NPCs induced by ischemia/hypoxia and might
      participate in injury remodeling.

PMID- 19762702
TI  - Cerebral microbleeds in ischemic stroke patients on warfarin treatment.
AB  - BACKGROUND AND PURPOSE: Cerebral microbleeds (CMBs) are known to be indicative of
      bleeding prone microangiopathy. Little is known about its significance in
      anticoagulated patients. We aimed to determine the frequency of CMBs in ischemic
      stroke patients on warfarin treatment. METHODS: A total of 141 ischemic stroke
      patients on warfarin therapy were enrolled in this study. One hundred five
      patients with similar demographic features who do not use warfarin were chosen as
      controls. We compared vascular risk factors and radiological findings including
      CMBs and leukoaraiosis between the groups. RESULTS: CMBs on gradient-echo MRI (GE
      MRI) were found in 31 patients (22%) and 17 controls (16%) and there was not a
      significant difference between 2 groups (P=0.25). Study patients with CMBs were
      older than patients without CMBs (P=0.04) and frequency of leukoaraiosis was
      significantly higher (P=0.008). Mean duration of warfarin treatment was not
      different between the patients with and without CMBs (P=0.83). CONCLUSIONS:
      Although patients with CMBs were older and had more leukoaraiosis the impact of
      warfarin treatment on CMBs is still controversial.

PMID- 19762703
TI  - Diagnosing delayed cerebral ischemia with different CT modalities in patients
      with subarachnoid hemorrhage with clinical deterioration.
AB  - BACKGROUND AND PURPOSE: Delayed cerebral ischemia (DCI) after aneurysmal
      subarachnoid hemorrhage worsens the prognosis and is difficult to diagnose. We
      investigated the diagnostic value of noncontrast CT (NCT), CT perfusion (CTP),
      and CT angiography (CTA) for DCI after clinical deterioration in patients with
      subarachnoid hemorrhage. METHODS: We prospectively enrolled 42 patients with
      subarachnoid hemorrhage with clinical deterioration suspect for DCI (new focal
      deficit or Glasgow Coma Scale decrease >or=2 points) within 21 days after
      hemorrhage. All patients underwent NCT, CTP, and CTA scans on admission and
      directly after clinical deterioration. The gold standard was the clinical
      diagnosis DCI made retrospectively by 2 neurologists who interpreted all clinical
      data, except CTP and CTA, to rule out other causes for the deterioration.
      Radiologists interpreted NCT and CTP images for signs of ischemia (NCT) or
      hypoperfusion (CTP) not localized in the neurosurgical trajectory or around
      intracerebral hematomas, and CTA images for presence of vasospasm. Diagnostic
      values for DCI of NCT, CTP, and CTA were assessed by calculating sensitivities,
      specificities, positive predictive values, and negative predictive values with
      95% CIs. RESULTS: In 3 patients with clinical deterioration, imaging failed due
      to motion artifacts. Of the remaining 39 patients, 25 had DCI and 14 did not. NCT
      had a sensitivity of 0.56 (95% CI, 0.37 to 0.73), specificity=0.71 (0.57 to
      0.77), positive predictive value=0.78 (0.55 to 0.91), negative predictive
      value=0.48 (0.28 to 0.68); CTP: sensitivity=0.84 (0.65 to 0.94), specificity=0.79
      (0.52 to 0.92), positive predictive value=0.88 (0.69 to 0.96), negative
      predictive value=0.73 (0.48 to 0.89); CTA: sensitivity=0.64 (0.45 to 0.80),
      specificity=0.50 (0.27 to 0.73), positive predictive value=0.70 (0.49 to 0.84),
      negative predictive value=0.44 (0.23 to 0.67). CONCLUSIONS: As a diagnostic tool
      for DCI, qualitative assessment of CTP is overall superior to NCT and CTA and
      could be useful for fast decision-making and guiding treatment.

PMID- 19762705
TI  - Patients with Alzheimer disease with multiple microbleeds: relation with
      cerebrospinal fluid biomarkers and cognition.
AB  - BACKGROUND AND PURPOSE: Microbleeds (MBs) are commonly observed in Alzheimer
      disease. A minority of patients has multiple MBs. We aimed to investigate
      associations of multiple MBs in Alzheimer disease with clinical and MRI
      characteristics and cerebrospinal fluid biomarkers. METHODS: Patients with
      Alzheimer disease with multiple (>or=8) MBs on T2*-weighted MRI were matched for
      age, sex, and field strength with patients with Alzheimer disease without MBs on
      a 1:2 basis. We included 21 patients with multiple MBs (73+/-7 years, 33% female)
      and 42 patients without MBs (72+/-7 years, 38% female). Mini-Mental State
      Examination was used to assess dementia severity. Cognitive functions were
      assessed using neuropsychological tests. Medial temporal lobe atrophy (0 to 4),
      global cortical atrophy (0 to 3), and white matter hyperintensities (0 to 30)
      were assessed using visual rating scales. In a subset, apolipoprotein E genotype
      and cerebrospinal fluid amyloid beta 1-42, total tau and tau phosphorylated at
      threonine 181 were determined. RESULTS: Patients with multiple MBs performed
      worse on Mini-Mental State Examination (multiple MB: 17+/-7; no MB: 22+/-4,
      P<0.05) despite similar disease duration. Atrophy was not related to presence of
      MBs, but patients with multiple MBs had more white matter hyperintensities
      (multiple MB: 8.8+/-4.8; no MB: 3.2+/-3.6, P<0.05). Adjusted for age, sex, white
      matter hyperintensities, and medial temporal lobe atrophy, the multiple MB group
      additionally performed worse on Visual Association Test object naming and animal
      fluency. Patients with multiple MBs had lower cerebrospinal fluid amyloid beta 1
      42 levels (307+/-61) than patients without MBs (505+/-201, P<0.05). Adjusted for
      the same covariates, total tau, and tau phosphorylated at threonine 181 were
      higher in the multiple MB group. CONCLUSIONS: Microbleeds are associated with the
      clinical manifestation and biochemical hallmarks of Alzheimer disease, suggesting
      possible involvement of MBs in the pathogenesis of Alzheimer disease.

PMID- 19762706
TI  - Prophylactic, endovascularly based, long-term normothermia in ICU patients with
      severe cerebrovascular disease: bicenter prospective, randomized trial.
AB  - BACKGROUND AND PURPOSE: We sought to study the effectiveness and safety of
      endovascular cooling to maintain prophylactic normothermia in comparison with
      standardized, stepwise, escalating fever management to reduce fever burden in
      patients with severe cerebrovascular disease. METHODS: This study was a
      prospective, randomized, controlled trial with a blinded neurologic outcome
      evaluation comparison between prophylactic, catheter-based normothermia
      (CoolGard; ie, body core temperature 36.5 degrees C) and conventional, stepwise
      fever management with anti-inflammatory drugs and surface cooling. Patients
      admitted to 1 of the 2 neurointensive care units were eligible for study
      inclusion when they had a (1) spontaneous subarachnoid hemorrhage with Hunt &
      Hess grade between 3 and 5, (2) spontaneous intracerebral hemorrhage with a
      Glasgow Coma Scale score <or=10, or (3) complicated cerebral infarction requiring
      intensive care unit treatment with a National Institutes of Health Stroke Scale
      score >or=15. RESULTS: A total of 102 patients (56 female) were enrolled during a
      3.5-year period. Fifty percent had a spontaneous subarachnoid hemorrhage, 40% had
      a spontaneous intracerebral hemorrhage, and 10% had a complicated cerebral
      infarction. Overall median total fever burden during the course of treatment was
      0.0 degrees C hour and 4.3 degrees C hours in the catheter and conventional
      groups, respectively (P<0.0001). Prophylactic normothermia did not lead to an
      increase in the number of patients who experienced a major adverse event. No
      significant difference was found in mortality and neurologic long-term follow-up.
      CONCLUSIONS: Long-term, catheter-based, prophylactic normothermia significantly
      reduces fever burden in neurointensive care unit patients with severe
      cerebrovascular disease and is not associated with increased major adverse
      events.

PMID- 19762707
TI  - Noninvasive detection of vertebral artery stenosis: a comparison of contrast
      enhanced MR angiography, CT angiography, and ultrasound.
AB  - BACKGROUND AND PURPOSE: Vertebral stenosis is associated with a high risk of
      recurrent stroke, but noninvasive imaging techniques to identify it have lacked
      sensitivity. Contrast-enhanced MR angiography and CT angiography have been
      recently developed and appear to have better sensitivity. However, no prospective
      studies have compared both of these techniques with ultrasound against the gold
      standard of intra-arterial angiography in the same group of patients. METHODS:
      Forty-six patients were prospectively recruited in whom intra-arterial
      angiography was being performed. Contrast-enhanced MR angiography, CT
      angiography, and duplex ultrasound were also performed. Angiographic images were
      analyzed blinded to patient identity by 2 experienced neuroradiologists. RESULTS:
      Contrast-enhanced MR angiography had the highest sensitivity and specificity
      (Radiologist 1, 0.83 and 0.91, respectively; Radiologist 2, 0.89 and 0.87) for
      detecting >or=50% stenosis. CT angiography had good sensitivity (Radiologist 1,
      0.68; Radiologist 2, 0.58) and excellent specificity (Radiologist 1, 0.92;
      Radiologist 2, 0.93), whereas duplex had low sensitivity (0.44) but excellent
      specificity (0.95). For vertebral origin stenosis >or=50%, sensitivities were
      similar for contrast-enhanced MR angiography (Radiologist 1, 0.91; Radiologist 2,
      0.82) but relatively higher for CT angiography (Radiologist 1, 0.82; Radiologist
      2, 0.82) and duplex (0.67). CONCLUSIONS: Contrast-enhanced MR angiography is the
      most sensitive noninvasive technique to detect vertebral artery stenosis and also
      has high specificity. CT angiography has good sensitivity and high specificity.
      In contrast, ultrasound has low sensitivity and will miss many vertebral
      stenoses.

PMID- 19762708
TI  - Local symptoms and recanalization in spontaneous carotid artery dissection.

PMID- 19762709
TI  - HINTS to diagnose stroke in the acute vestibular syndrome: three-step bedside
      oculomotor examination more sensitive than early MRI diffusion-weighted imaging.
AB  - BACKGROUND AND PURPOSE: Acute vestibular syndrome (AVS) is often due to
      vestibular neuritis but can result from vertebrobasilar strokes. Misdiagnosis of
      posterior fossa infarcts in emergency care settings is frequent. Bedside
      oculomotor findings may reliably identify stroke in AVS, but prospective studies
      have been lacking. METHODS: The authors conducted a prospective, cross-sectional
      study at an academic hospital. Consecutive patients with AVS (vertigo, nystagmus,
      nausea/vomiting, head-motion intolerance, unsteady gait) with >or=1 stroke risk
      factor underwent structured examination, including horizontal head impulse test
      of vestibulo-ocular reflex function, observation of nystagmus in different gaze
      positions, and prism cross-cover test of ocular alignment. All underwent
      neuroimaging and admission (generally <72 hours after symptom onset). Strokes
      were diagnosed by MRI or CT. Peripheral lesions were diagnosed by normal MRI and
      clinical follow-up. RESULTS: One hundred one high-risk patients with AVS included
      25 peripheral and 76 central lesions (69 ischemic strokes, 4 hemorrhages, 3
      other). The presence of normal horizontal head impulse test, direction-changing
      nystagmus in eccentric gaze, or skew deviation (vertical ocular misalignment) was
      100% sensitive and 96% specific for stroke. Skew was present in 17% and
      associated with brainstem lesions (4% peripheral, 4% pure cerebellar, 30%
      brainstem involvement; chi(2), P=0.003). Skew correctly predicted lateral pontine
      stroke in 2 of 3 cases in which an abnormal horizontal head impulse test
      erroneously suggested peripheral localization. Initial MRI diffusion-weighted
      imaging was falsely negative in 12% (all <48 hours after symptom onset).
      CONCLUSIONS: Skew predicts brainstem involvement in AVS and can identify stroke
      when an abnormal horizontal head impulse test falsely suggests a peripheral
      lesion. A 3-step bedside oculomotor examination (HINTS: Head-Impulse-Nystagmus
      Test-of-Skew) appears more sensitive for stroke than early MRI in AVS.

PMID- 19762710
TI  - Loss-of-function FERMT1 mutations in kindler syndrome implicate a role for
      fermitin family homolog-1 in integrin activation.
AB  - Kindler syndrome is an autosomal recessive disorder characterized by skin atrophy
      and blistering. It results from loss-of-function mutations in the FERMT1 gene
      encoding the focal adhesion protein, fermitin family homolog-1. How and why
      deficiency of fermitin family homolog-1 results in skin atrophy and blistering
      are unclear. In this study, we investigated the epidermal basement membrane and
      keratinocyte biology abnormalities in Kindler syndrome. We identified altered
      distribution of several basement membrane proteins, including types IV, VII, and
      XVII collagens and laminin-332 in Kindler syndrome skin. In addition, reduced
      immunolabeling intensity of epidermal cell markers such as beta1 and alpha6
      integrins and cytokeratin 15 was noted. At the cellular level, there was loss of
      beta4 integrin immunolocalization and random distribution of laminin-332 in
      Kindler syndrome keratinocytes. Of note, active beta1 integrin was reduced but
      overexpression of fermitin family homolog-1 restored integrin activation and
      partially rescued the Kindler syndrome cellular phenotype. This study provides
      evidence that fermitin family homolog-1 is implicated in integrin activation and
      demonstrates that lack of this protein leads to pathological changes beyond focal
      adhesions, with disruption of several hemidesmosomal components and reduced
      expression of keratinocyte stem cell markers. These findings collectively provide
      novel data on the role of fermitin family homolog-1 in skin and further insight
      into the pathophysiology of Kindler syndrome.

PMID- 19762711
TI  - Role of CD11b+ macrophages in intraperitoneal lipopolysaccharide-induced aberrant
      lymphangiogenesis and lymphatic function in the diaphragm.
AB  - Lymphatic vessels in the diaphragm are essential for draining peritoneal fluid,
      but little is known about their pathological changes during inflammation. Here we
      characterized diaphragmatic lymphatic vessels in a peritonitis model generated by
      daily i.p. administration of lipopolysaccharide (LPS) in mice. Intraperitoneal
      LPS increased lymphatic density, branching, sprouts, connections, and network
      formation in the diaphragm in time- and dose-dependent manners. These changes
      were reversible on discontinuation of LPS administration. The LPS-induced
      lymphatic density and remodeling occur mainly through proliferation of lymphatic
      endothelial cells. CD11b+ macrophages were massively accumulated and closely
      associated with the lymphatic vessels changed by i.p. LPS. Both RT-PCR assays and
      experiments with vascular endothelial growth factor-C/D blockade and macrophage
      depletion indicated that the CD11b+ macrophage-derived lymphangiogenic factors
      vascular endothelial growth factor-C/D could be major mediators of LPS-induced
      lymphangiogenesis and lymphatic remodeling through paracrine activity. Functional
      assays with India ink and fluorescein isothiocyanate-microspheres indicated that
      impaired peritoneal fluid drainage in diaphragm of LPS-induced peritonitis mice
      was due to inflammatory fibrosis and massive attachment of CD11b+ macrophages on
      the peritoneal side of the diaphragmatic lymphatic vessels. These findings reveal
      that CD11b+ macrophages play an important role in i.p. LPS-induced aberrant
      lymphangiogenesis and lymphatic dysfunction in the diaphragm.

PMID- 19762712
TI  - Is expression or activation of Src kinase associated with cancer-specific
      survival in ER-, PR- and HER2-negative breast cancer patients?
AB  - The aim of the current study was to assess the expression levels of c-Src and
      phosphorylated Src kinase in human breast cancers and to establish if these are
      linked to oestrogen receptor, progesterone receptor, and human epidermal growth
      factor receptor 2 status or patient survival. Tissue microarray technology was
      used to analyze 314 breast cancer specimens. Immunohistochemistry was performed
      using antibodies to c-Src, Y419Src, and Y215Src, and expression was assessed
      using the weighted histoscore method. High cytoplasmic c-Src kinase and high
      membrane phosphorylated activated Y419Src kinase was associated with decreased
      disease-specific survival. In contrast, phosphorylated activated nuclear and
      cytoplasmic Y215Src kinase expression levels were significantly associated with
      improved disease-specific survival. When the cohort was subdivided according to
      ER/PR/HER2 status, the ER-negative subgroup (105 patients) was associated with
      improved disease-specific survival and was found to be independent by
      multivariate analysis with a hazard ratio of 0.4 (interquartile range 0.2-0.8).
      High cytoplasmic c-Src expression was associated with decreased survival; high
      expression of activated c-Src (Y215) was associated with improved survival. This
      was potentiated in the ER/HER2-negative subgroup. Hence, administration of Src
      kinase inhibitors aiming to decrease phosphorylation should be approached with
      caution, especially in ER-negative patients. It is therefore essential to
      appropriately identify with the correct biomarkers which patients are most likely
      to respond to Src inhibitors.

PMID- 19762713
TI  - An inducible cartilage oligomeric matrix protein mouse model recapitulates human
      pseudoachondroplasia phenotype.
AB  - Cartilage oligomeric matrix protein (COMP) is a pentameric extracellular protein
      expressed in cartilage and other musculoskeletal tissues. Mutations in the COMP
      gene cause pseudoachondroplasia (PSACH), a severe dwarfing condition that has a
      growth plate chondrocyte pathology. PSACH is characterized by intracellular
      retention of COMP and other extracellular matrix (ECM) proteins, which form an
      ordered matrix within large rough endoplasmic reticulum cisternae. This
      accumulation is cytotoxic and causes premature chondrocyte cell death, thereby
      depleting chondrocytes needed for normal long bone growth. Research to define the
      underlying molecular mechanisms of PSACH has been hampered by the lack of a
      suitable model system. In this study, we achieved robust expression of human
      mutant (MT) or wild-type (WT) COMP in mice by using a tetracycline-inducible
      promoter. Normal growth plate distribution of ECM proteins was observed in 1
      month-old WT-COMP and C57BL?6 control mice. In contrast, the structure of the MT
      COMP growth plate recapitulated the findings of human PSACH growth plate
      morphology, including (1) retention of ECM proteins, (2) intracellular matrix
      formation in the rER cisternae, and (3) increased chondrocyte apoptosis.
      Therefore, we have generated the first mouse model to show extensive
      intracellular retention of ECM proteins recapitulating the human PSACH disease
      process at the cellular level.

PMID- 19762714
TI  - Role of MKP-1 in osteoclasts and bone homeostasis.
AB  - Bone mass is maintained through the complementary activities of osteoblasts and
      osteoclasts; yet differentiation of either osteoblasts and osteoclasts engages
      the mitogen-activated protein kinase (MAPK) pathway. The MAPKs are negatively
      regulated by a family of dual-specificity phosphatases known as the MAPK
      phosphatases (MKPs). MKP-1 is a stress-responsive MKP that inactivates the MAPKs
      and plays a central role in macrophages; however, whether MKP-1 plays a role in
      the maintenance of bone mass has yet to be investigated. We show here, using a
      genetic approach, that mkp-1(-/-) female mice exhibited slightly reduced bone
      mass. We found that mkp-1(+/+) and mkp-1(-/-) mice had equivalent levels of bone
      loss after ovariectomy despite mkp-1(-/-) mice having fewer osteoclasts,
      suggesting that mkp-1(-/-) osteoclasts are hyperactive. Indeed, deletion of MKP1
      led to a profound activation of osteoclasts in vivo in response to local
      lipopolysaccharide (LPS) injection. These results suggest a role for MKP-1 in
      osteoclasts, which originate from the fusion of macrophages. In support of these
      observations, receptor activator for nuclear factor-kappaB ligand induced the
      expression for MKP-1, and osteoclasts derived from mkp-1(-/-) mice had increased
      resorptive activity. Finally, receptor activator of nuclear factor-kappaB ligand
      induced p38 MAPK and c-Jun NH2-terminal kinase activities were enhanced in
      osteoclasts derived from mkp-1(-/-) mice. Taken together, these results show that
      MKP-1 plays a role in the maintenance of bone mass and does so by negatively
      regulating MAPK-dependent osteoclast signaling.

PMID- 19762716
TI  - Do women feel worse to look their best? Testing the relationship between self
      esteem and fertility status across the menstrual cycle.
AB  - Two studies measured self-esteem across the menstrual cycle to test the
      prediction that self-esteem will vary interindividually as a positive function of
      mate value and intraindividually as a negative function of fertility status.
      Study 1 (n = 52) found that self-esteem was positively related to mate value
      between women but that women experienced a self-esteem decrease nearest to
      ovulation, when women tend to be more attractive to men. Study 2 (n = 59)
      replicated these results and demonstrated that the self-esteem decrease at high
      fertility was positively related to women's reported long-term mating motivation.
      Additionally, the magnitude of the self-esteem decrease at high fertility was
      found to be related to increased willingness to spend money on items to enhance
      attractiveness at high fertility. A self-esteem decrease at high fertility may
      motivate mate value enhancement efforts when such efforts are most critical.

PMID- 19762715
TI  - Kindlin-1 Is required for RhoGTPase-mediated lamellipodia formation in
      keratinocytes.
AB  - Kindlin-1 is an epithelial-specific member of the novel kindlin protein family,
      which are regulators of integrin functions. Mutations in the gene that encodes
      Kindlin-1, FERMT1 (KIND1), cause the Kindler syndrome (KS), a human disorder
      characterized by mucocutaneous fragility, progressive skin atrophy, ulcerative
      colitis, photosensitivity, and propensity to skin cancer. Our previous studies
      indicated that loss of kindlin-1 resulted in abnormalities associated with
      integrin functions, such as adhesion, proliferation, polarization, and motility
      of epidermal cells. Here, we disclosed novel FERMT1 mutations in KS and used
      them, in combination with small-interfering RNA, protein, and imaging studies, to
      uncover new functions for kindlin-1 in keratinocytes and to discern the molecular
      pathology of KS. We show that kindlin-1 forms molecular complexes with beta1
      integrin, alpha-actinin, migfilin, and focal adhesion kinase and regulates cell
      shape and migration by controlling lamellipodia formation. Kindlin-1 governs
      these processes by signaling via Rho family GTPases, and it is required to
      maintain the pool of GTP-bound, active Rac1, RhoA and Cdc42, and the
      phosphorylation of their downstream effectors p21-activated kinase 1, LIM kinase,
      and cofilin. Loss of these kindlin-1 functions forms the biological basis for the
      epithelial cell fragility and atrophy in the pathology of KS.

PMID- 19762717
TI  - Personality judgments based on physical appearance.
AB  - Despite the crucial role of physical appearance in forming first impressions,
      little research has examined the accuracy of personality impressions based on
      appearance alone. This study examined the accuracy of observers' impressions on
      10 personality traits based on full-body photographs using criterion measures
      based on self and peer reports. When targets' posture and expression were
      constrained (standardized condition), observers' judgments were accurate for
      extraversion, self-esteem, and religiosity. When targets were photographed with a
      spontaneous pose and facial expression (spontaneous condition), observers'
      judgments were accurate for almost all of the traits examined. Lens model
      analyses demonstrated that both static cues (e.g., clothing style) and dynamic
      cues (e.g., facial expression, posture) offered valuable personality-relevant
      information. These results suggest that personality is manifested through both
      static and expressive channels of appearance, and observers use this information
      to form accurate judgments for a variety of traits.

PMID- 19762718
TI  - The victim-informed prosecution project: a quasi-experimental test of a
      collaborative model for cases of intimate partner violence.
AB  - The Victim-Informed Prosecution Project (VIP) was designed to amplify the voice
      of the victim in the prosecution of a battering current or ex-partner through
      collaboration between the prosecution and victim-centered agencies. This article
      describes the rationale for and design and implementation of VIP and then
      explores whether it increased perceived voice. While some VIP services (advocacy
      and civil protection order representation) were associated with increased
      perceived voice, the program as a whole was associated with it only in the
      context of greater contact with prosecutors, when cases were more likely to be
      felonies. We make specific recommendations for applying this model.

PMID- 19762719
TI  - Violence against women and the U.S. Supreme Court: recent challenges and
      opportunities for advocates and practitioners.
AB  - The U.S. Supreme Court has frequently grappled with violence against women, with
      three major cases decided since 2000. Although the law can be a powerful tool to
      minimize the risk of violence against women, it can also be an obstacle to
      interventions. As legislators, prosecutors, and advocates implement legal
      interventions to respond to violence against women, the Supreme Court has
      increasingly been called on to interpret these laws and assess their
      constitutionality. This legal note examines recent Supreme Court jurisprudence
      that addresses interventions to prevent violence against women and explain how
      practitioners can tailor interventions to respond to these decisions.

PMID- 19762721
TI  - The association of malignant hyperthermia and unusual disease: when you're hot
      you're hot or maybe not.

PMID- 19762722
TI  - Malignant hyperthermia-associated diseases: state of the art uncertainty.

PMID- 19762723
TI  - Why are cerebral microemboli not associated with cognitive decline?

PMID- 19762724
TI  - The effects of cardiopulmonary bypass on the number of cerebral microemboli and
      the incidence of cognitive dysfunction after coronary artery bypass graft
      surgery.
AB  - BACKGROUND: Postoperative cognitive dysfunction (POCD) can be a debilitating
      complication after coronary artery bypass graft (CABG) surgery. Cerebral
      microemboli during cardiopulmonary bypass (CPB) are believed to be an important
      etiologic factor of POCD. In this study, we examined whether avoidance of CPB
      with "off-pump" surgery reduces the number of cerebral microemboli and the
      incidence of POCD after CABG surgery in Chinese population. METHODS: Two hundred
      twenty-seven patients were enrolled in this prospective cohort study. Fifty-nine
      patients underwent CABG surgery with CPB and 168 underwent off-pump surgery.
      Cerebral microemboli were measured continuously with bilateral transcranial
      Doppler ultrasonography of the middle cerebral arteries. A neuropsychological
      test battery that included seven tests with nine subscales was administered at
      baseline, as well as at 1 wk and 3 mo after surgery. POCD was defined using the
      international study of POCD1 definition. RESULTS: The median total number of
      cerebral microemboli for the case was 430 (range: 155-2088) in patients
      undergoing surgery with CPB and 2 (0-66) in the off-pump patients (P < 0.001).
      There were no differences in the incidence of POCD between the patients having
      surgery with or without CPB either at 1 wk (55.2% or 32 of 58 patients [95%
      confidence interval: 41.5%-68.3%] vs 47.0% or 78 of 166 patients [39.2%-54.9%], P
      = 0.283) or 3 mo (6.4% or 3 of 47 patients [1.3%-17.5%] vs 13.1% or 16 of 122 of
      patients [7.7%-20.4%], P = 0.214) after surgery. Increasing age and shorter
      duration of postoperative hospital stay were independently associated with
      cognitive dysfunction at 1 wk after surgery. Increasing age and a history of
      diabetes mellitus were independently associated with cognitive dysfunction 3 mo
      after surgery. CPB or cerebral microemboli were not significantly related to the
      occurrence of POCD. CONCLUSIONS: In Chinese population, avoidance of CPB during
      CABG surgery significantly decreased the number of cerebral microemboli, but it
      did not decrease the incidence of POCD at either 1 wk or 3 mo after CABG. Neither
      CPB nor cerebral microemboli was independently associated with the risk of POCD.

PMID- 19762725
TI  - In vitro inhibition of factor XIII retards clot formation, reduces clot firmness,
      and increases fibrinolytic effects in whole blood.
AB  - BACKGROUND: Thrombelastography has received renewed interest in the perioperative
      setting. The main determinants of thrombelastographic results are coagulation
      factor concentrations (various zymogens and fibrinogen) and platelet count; thus,
      platelet inhibition renders these assays mainly coagulation factor dependent.
      Assays with and without platelet inhibition are thus increasingly used to trigger
      and monitor replacement therapy with blood products. In this study, we evaluated
      the effect of factor XIII inhibition and additional glycoprotein (GP) IIb/IIIa
      blockade on (platelet-inhibited) whole blood thrombelastography and whether a
      modified routine assay (using factor XIII antibody) can be used to detect factor
      XIII deficiency. METHODS: Normal whole blood was incubated with increasing
      amounts of a nonspecific antibody, an anti-GPIIb/IIIa antibody, or a neutralizing
      anti-factor XIII antibody; samples were analyzed with a tissue factor-activated
      and platelet-inhibited whole blood thrombelastographic assay. Clotting time, clot
      formation time, maximum clot firmness, and clot lysis at 60 min were evaluated in
      triplicate. Also, 25 whole blood routine samples were evaluated for factor XIII
      deficiency using a new thrombelastographic assay incorporating a factor XIII
      antibody and using a standard factor XIII assay for comparison. RESULTS: Although
      GPIIb/IIIa inhibition did not alter the results of the platelet-inhibited whole
      blood thrombelastography, factor XIII inhibition significantly reduced maximum
      clot firmness (P = 0.020) and increased clot formation time (P = 0.025) and clot
      lysis (P = 0.007), leaving clotting time unchanged; a ceiling effect seemed to be
      present with increasing antibody concentrations in whole blood (but not plasma).
      The thrombelastographic assay for factor XIII deficiency (<70% activity) had a
      90% sensitivity and negative predictive value (area under receiver operating
      characteristic curve 0.803, P = 0.0015); for a deficiency <60%, sensitivity and
      negative predictive value were 100% (area under receiver operating characteristic
      curve 0.84, P = 0.0037). CONCLUSION: Factor XIII has significant impact on
      platelet-inhibited activated whole blood thrombelastography. This phenomenon
      should be considered when interpreting thrombelastographic results in the
      bleeding patient, especially when the results trigger procoagulant therapy.
      Antibody-mediated factor XIII inhibition can be used to establish
      thrombelastography-based assays to detect factor XIII deficiency.

PMID- 19762726
TI  - Transesophageal echocardiography of an anomalous circumflex coronary artery:
      anatomy and implications.

PMID- 19762727
TI  - Functional tricuspid regurgitation in a patient with endocarditis.

PMID- 19762728
TI  - Penetrating ascending aortic atherosclerotic ulcer.

PMID- 19762729
TI  - Placing a saline bag underneath the displaced heart enhances transgastric
      transesophageal echocardiographic imaging during off-pump coronary artery bypass
      surgery.

PMID- 19762730
TI  - Malignant hyperthermia and muscular dystrophies.
AB  - BACKGROUND: Patients with muscular dystrophy have been reported to experience a
      variety of life-threatening complications during and after general anesthesia. We
      performed a systematic analysis to define the spectrum of anesthetic-related
      complications in patients with muscular dystrophy, with an emphasis on malignant
      hyperthermia susceptibility. METHODS: A literature search was undertaken using
      multiple search engines and the appropriate articles were reviewed by the authors
      to determine anesthetic-associated complications in patients with muscular
      dystrophy. Of all the types of muscular dystrophy, Duchenne muscular dystrophy
      (DMD) and Becker dystrophy (BD) represent nearly all the anesthesia-related
      reports. RESULTS: Anesthetic complications in patients with DMD and BD include
      intraoperative heart failure, inhaled anesthetic-related rhabdomyolysis (absence
      of succinylcholine), and succinylcholine-induced rhabdomyolysis and hyperkalemia.
      CONCLUSION: We did not find an increased risk of malignant hyperthermia
      susceptibility in patients with DMD or BD compared with the general population.
      However, dystrophic patients who are exposed to inhaled anesthetics may develop
      disease-related cardiac complications, or rarely, a malignant hyperthermia-like
      syndrome characterized by rhabdomyolysis. This latter complication may also occur
      postoperatively. Succinylcholine administration is associated with life
      threatening hyperkalemia and should be avoided in patients with DMD and BD.

PMID- 19762731
TI  - Malignant hyperthermia, coexisting disorders, and enzymopathies: risks and
      management options.
AB  - Clinical episodes and abnormal laboratory tests compatible with a diagnosis of
      malignant hyperthermia have been observed in patients with a diversity of
      syndromes, enzymopathies, and coexisting disorders thereby raising the likelihood
      of causal associations and heightened perioperative risk in others carrying a
      shared diagnosis. In the present review, we survey available published series,
      case reports, and the results of contracture testing in patients identified by
      others to be potentially predisposed to malignant hyperthermia. For most
      conditions, evidence for a causal relationship with malignant hyperthermia
      susceptibility is weak. The review concludes with suggestions for clinical
      management when evidence for or against an association is uncertain.

PMID- 19762732
TI  - The myotonias and susceptibility to malignant hyperthermia.
AB  - Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle in
      which volatile anesthetics trigger a sustained increase in intramyoplasmic Ca(2+)
      via release from sarcoplasmic reticulum and, possibly, entry from the
      extracellular milieu that leads to hypermetabolism, muscle rigidity,
      rhabdomyolysis, and death. Myotonias are a class of myopathies that result from
      gene mutations in various channels involved in skeletal muscle excitation
      contraction coupling and sarcolemmal excitability, and unusual DNA sequence
      repeats that result in the inability of many proteins, including skeletal muscle
      channels that affect excitability, to undergo proper splicing. The suggestion has
      often been made that myotonic patients have an increased risk of developing MH.
      In this article, we review the physiology of muscle excitability and excitation
      contraction coupling, the pathophysiology of MH and the myotonias, and review the
      clinical literature upon which the claims of MH susceptibility are based. We
      conclude that patients with these myopathies have a risk of developing MH that is
      equivalent to that of the general population with one potential exception,
      hypokalemic periodic paralysis. Despite the fact that there are no clinical
      reports of MH developing in patients with hypokalemic periodic paralysis, for
      theoretical reasons we cannot be as certain in estimating their risk of
      developing MH, even though we believe it is low.

PMID- 19762733
TI  - Malignant hyperthermia-like syndrome and carnitine palmitoyltransferase II
      deficiency with heterozygous R503C mutation.
AB  - We describe a child who developed a malignant hyperthermia-like syndrome after
      exposure to succinylcholine and halothane. Many features of a typical malignant
      hyperthermia episode were present, including tachydysrhythmia, tachypnea, and
      fever in association with metabolic acidosis, hyperCKemia, myglobinemia, and
      rapid recovery without residual effects upon administration of dantrolene, sodium
      bicarbonate, and active cooling. Muscle rigidity, hypercarbia, and hyperkalemia
      were not observed. The patient was found to be heterozygous for a mutation in the
      carnitine palmitoyltransferase II gene (CPT2) encoding an arginine to cysteine
      substitution at amino acid 503 (R503C) with reduced activity of the enzyme.

PMID- 19762734
TI  - A comparison of high volume/low concentration and low volume/high concentration
      ropivacaine in caudal analgesia for pediatric orchiopexy.
AB  - BACKGROUND: It is unclear whether the volume or concentration of local anesthetic
      influences its spread and quality of caudal analgesia when the total drug dose is
      fixed. METHODS: We performed this study in a prospective, randomized, observer
      blind manner. Children aged 1-5 yr received a constant dose of 2.25 mg/kg of
      ropivacaine prepared as either 1.0 mL/kg of 0.225% (low volume/high concentration
      [LVHC], n = 37) or 1.5 mL/kg of 0.15% solution (high volume/low concentration
      [HVLC], n = 36). Both solutions contained radiopaque dye. RESULTS: The median
      spread levels with ranges in the HVLC group (confirmed by fluoroscopic
      examination) were significantly higher (T6, T3-11) than in the LVHC group (T11,
      T8-L2). There were no significant differences in recovery times, postoperative
      pain scores, or side effects between the two groups. After discharge, fewer
      children in the HVLC group required rescue oral acetaminophen compared with the
      LVHC group (50.0% vs 75.7%). First oral acetaminophen time was found to be
      significantly longer with HVLC patients than LVHC patients (363.0 min vs 554.5
      min). CONCLUSIONS: We confirmed (with fluoroscopy) that a caudal block with 1
      mL/kg ropivacaine spreads to T11 and to T6 with 1.5 mL/kg. If the total dose is
      fixed, caudal analgesia with a larger volume of diluted ropivacaine (0.15%)
      provides better quality and longer duration after discharge than a smaller volume
      of more concentrated ropivacaine (0.225%) in children undergoing day-case
      orchiopexy. The spread level of ropivacaine correlated significantly with the
      first oral acetaminophen time after discharge.

PMID- 19762735
TI  - The risk factors for hypoxemia in children younger than 5 years old undergoing
      rigid bronchoscopy for foreign body removal.
AB  - BACKGROUND: Removal of an airway foreign body (FB) is usually performed by rigid
      bronchoscopy under general anesthesia, but the choice of anesthesia and
      ventilation techniques varies greatly among anesthesiologists and institutions.
      Hypoxemia is the most commonly observed adverse event during rigid bronchoscopy.
      It is influenced by a variety of factors including the patient's medical
      condition, the type of surgical procedure, and the anesthetic technique. In the
      current study, we investigated risk factors that statistically correlate with
      intraoperative or postoperative hypoxemia in young patients undergoing rigid
      bronchoscopy. METHODS: From January 2007 to December 2008, 384 children younger
      than 5-yr-of-age subjected to rigid bronchoscopy for FB removal were included in
      the study. The detailed clinical information and perioperative adverse events
      were recorded. Surgical outcomes and incidence of perioperative adverse events
      were compared among different ventilation modes (spontaneous ventilation, manual
      intermittent positive pressure ventilation, and manual jet ventilation) and
      different anesthetic techniques (total IV anesthesia and inhaled anesthesia). An
      amalgamated dataset was used for the analysis of factors that correlated with
      perioperative hypoxemia. RESULTS: In children who received total IV anesthesia
      with spontaneous ventilation during rigid bronchoscopy, we observed more
      intraoperative body movement and breath holding, significantly longer duration of
      emergence from anesthesia, lower percentage of successful FB removal, and more
      postoperative laryngospasm. Children in the manual jet ventilation group had the
      least occurrence of intraoperative hypoxemia. Five factors strongly correlated
      with intraoperative hypoxemia. Younger age, plant seed as the type of FB, longer
      surgical duration, pneumonia before the procedure, and spontaneous ventilation
      mode significantly increased the risk of intraoperative hypoxemia, whereas manual
      jet ventilation mode decreased it. Two factors were associated with postoperative
      hypoxemia: plant seed as a FB and prolonged duration of emergence from
      anesthesia. CONCLUSION: We identified risk factors associated with intraoperative
      or with postoperative hypoxemia in rigid bronchoscopy which included patient age,
      type of FB, duration of surgical procedure, pneumonia before the procedure,
      ventilation mode, and duration of emergence from anesthesia. These results
      provide evidence that will help clinicians to reduce the incidence of hypoxemia
      in high-risk children.

PMID- 19762736
TI  - Children's desire for perioperative information.
AB  - BACKGROUND: The purpose of this investigation was to identify what perioperative
      information children want to receive from the medical staff. METHODS: As a first
      step, we developed an instrument based on a qualitative study conducted with
      children in Great Britain, input from a focus group, and input from school
      children. On the day of surgery, 143 children aged 7-17 yr completed a 40-item
      assessment of desired surgical information and a measure of anxiety (State-Trait
      Anxiety Inventory for Children). Parents completed a measure assessing their
      child's temperament (Emotionality, Activity, Sociability, and Impulsivity Survey)
      and a measure of their own anxiety (State-Trait Anxiety Inventory). RESULTS:
      Results indicated that the vast majority of children had a desire for
      comprehensive information about their surgery, including information about pain
      and anesthesia, and procedural information and information about potential
      complications. The most highly endorsed items by children involved information
      about pain. Children who were more anxious endorsed a stronger desire for pain
      information and lesser tendency to avoid information. Younger children wanted to
      know what the perioperative environment would look like more than adolescent
      children. CONCLUSIONS: We conclude that the majority of children aged 7-17 yr who
      undergo surgery want to be given comprehensive perioperative information and
      health care providers should ensure adequate information regarding postoperative
      pain is provided.

PMID- 19762737
TI  - Neuromuscular block differentially affects immobility and cortical activation at
      near-minimum alveolar concentration anesthesia.
AB  - BACKGROUND: Anesthesia-induced immobility and cortical suppression are governed
      by anatomically separate, but interacting, areas of the central nervous system.
      Consequently, larger volatile anesthetic concentrations are required to suppress
      cortical activation than to abolish movement in response to noxious stimulation.
      We examined the effect of decreased afferent input, as produced by neuromuscular
      block (NMB), on immobility and cortical activation, as measured by bispectral
      index (BIS) of the electrocardiogram, in the presence of noxious stimulation
      during approximately minimum alveolar concentrations (MACs) of desflurane
      anesthesia. METHODS: The effect of NMB on the median effective end-tidal
      concentration of desflurane (EtDes(50), or MAC(tetanus)) for immobility was
      estimated using the up-and-down method and isolated forearm technique in 24
      healthy volunteers. Each volunteer sequentially received saline, mivacurium, and
      succinylcholine in a randomized order, while EtDes concentration during each of
      the treatments was determined based on the movement response of the previous
      volunteer on the same treatment. Nonlinear mixed-effects modeling was used to
      evaluate the effect of NMB on BIS versus EtDes concentration relationship at
      baseline and after noxious stimulation, while the frontal electromyogram
      (EMG(BIS)) effect on BIS was also modeled as a covariate. Cardiovascular
      responses to noxious stimulation were compared across treatments. RESULTS:
      Succinylcholine and mivacurium significantly reduced MAC(tetanus) (95% confidence
      interval) from 5.00% (4.85%-5.13%), during saline, to 4.05% (3.81%-4.29%) and
      3.84% (3.60%-4.08%), respectively. Noxious stimulation significantly, although
      minimally, increased BIS response during all treatments. Succinylcholine
      increased BIS independently of an effect on EMG(BIS). Succinylcholine
      administration increased cardiovascular activity. Interestingly, although
      cardiovascular reaction to the noxious event was ablated by mivacurium, cortical
      response, as determined by BIS, was retained. CONCLUSIONS: Both succinylcholine
      and mivacurium enhanced immobility during near-MAC anesthesia. All treatments
      were associated with a small, although significant, BIS increase in response to
      noxious stimulation, whereas succinylcholine increased BIS independently of
      noxious stimulation or EMG(BIS). Mivacurium suppressed autonomic response to a
      noxious event.

PMID- 19762738
TI  - Nitrous oxide-induced analgesia does not influence nitrous oxide's immobilizing
      requirements.
AB  - BACKGROUND: Nitrous oxide (N(2)O) acts on supraspinal noradrenergic neurons to
      produce analgesia, but it is unclear if analgesia contributes to N(2)O's
      immobilizing effects. We tested the hypothesis that N(2)O minimum alveolar
      anesthetic concentration (MAC) is unchanged after selective ablation of
      supraspinal noradrenergic neurons, or in naive animals at N(2)O exposure
      timepoints when analgesia is absent. METHODS: We determined tailflick latency
      (TFL) and hindpaw withdrawal latency (HPL) under 70% N(2)O, N(2)O MAC, and
      isoflurane MAC before and after intracerebroventricular injections of anti
      dopamine-beta hydroxylase conjugated to saporin (SAP-DBH; n = 7), or a control
      antibody conjugated to saporin (n = 5). In a separate group of naive rats (n =
      8), N(2)O MAC was determined at 25-45 min after initiation of N(2)O exposure
      (during peak analgesia) and again at 120-140 min (after TFL and HPL returned to
      baseline). RESULTS: After 30 min of N(2)O exposure, TFL and HPL increased
      significantly but declined back to baseline within 120 min. N(2)O did not produce
      analgesia in rats that received SAP-DBH. However, N(2)O and isoflurane MAC were
      not significantly different between SAP-DBH and control-injected animals (Mean +/
      sd for N(2)O: 1.7 +/- 0.1 atm vs 1.7 +/- 0.2 atm; isofurane: 1.6 +/- 0.2% vs 1.7
      +/- 0.2%). In naive animals, N(2)O MAC was not different at the 30 min period
      compared with the 120 min period (1.8 +/- 0.1 atm vs 1.8 +/- 0.2 atm).
      CONCLUSIONS: Destroying brainstem noradrenergic neurons or prolonged exposure to
      N(2)O removes its analgesic effects, but does not change MAC. The immobilizing
      mechanism of N(2)O is independent from its analgesic effects.

PMID- 19762739
TI  - Stem cell-like human endothelial progenitors show enhanced colony-forming
      capacity after brief sevoflurane exposure: preconditioning of angiogenic cells by
      volatile anesthetics.
AB  - BACKGROUND: Endothelial progenitor cells play a pivotal role in tissue repair,
      and thus are used for cell replacement therapies in "regenerative medicine." We
      tested whether the anesthetic sevoflurane would modulate growth or mobilization
      of these angiogenic cells. METHODS: In an in vitro model, mononuclear cells
      isolated from peripheral blood of healthy donors were preconditioned with
      sevoflurane (3 times 30 min at 2 vol% interspersed by 30 min of air). Colony
      forming units were determined after 9 days in culture and compared with time
      matched untreated control. Using magnetic cell sorting, CD133+/CD34+ endothelial
      progenitors were enriched from human umbilical cord blood, and vascular
      endothelial growth factor (VEGF), VEGFR2 (KDR), granulocyte colony-stimulating
      factor (G-CSF), STAT3, c-kit, and CXCR4 expressions were determined in
      sevoflurane-treated and untreated cells by real-time reverse transcriptase
      polymerase chain reaction. In a volunteer study with crossover design, we tested
      whether sevoflurane inhalation (<1 vol% end-tidal concentration) would mobilize
      endothelial progenitor cells from the bone marrow niche into the circulation
      using flow cytometry of peripheral blood samples. VEGF and G-CSF plasma levels
      were also measured. RESULTS: In vitro sevoflurane exposure of mononuclear cells
      enhanced colony-forming capacity and increased VEGF mRNA levels in CD133+/CD34+
      cord blood cells (P = 0.017). Sevoflurane inhalation in healthy volunteers did
      not alter the number of CD133+/CD34+ or KDR+/CD34+ endothelial progenitors in the
      circulation, but increased the number of colony-forming units (P = 0.034),
      whereas VEGF and G-CSF plasma levels remained unchanged. CONCLUSIONS: Sevoflurane
      preconditioning promotes growth and proliferation of stem cell-like human
      endothelial progenitors. Hence, it may be used to promote perioperative vascular
      healing and to support cell replacement therapies.

PMID- 19762740
TI  - Isoflurane inhibits cyclic adenosine monophosphate response element-binding
      protein phosphorylation and calmodulin translocation to the nucleus of SH-SY5Y
      cells.
AB  - BACKGROUND: Calmodulin (CaM) activation by Ca(2+), its translocation to the
      nucleus, and stimulation of phosphorylation of cyclic adenosine monophosphate
      response element-binding protein (CREB) (P-CREB) are necessary for new gene
      expression and have been linked to long-term potentiation, a process important in
      memory formation. Because isoflurane affects memory, we tested whether isoflurane
      interfered with the translocation of CaM to the neuronal cell nucleus and
      attenuated the formation P-CREB. METHODS: SH-SY5Y cells, a human neuroblastoma
      cell line, were cultured. Cells were depolarized with KCl and the phosphorylation
      of CREB examined by Western blotting, enzyme-linked immunosorbant assay, and
      immunocytochemistry. The translocation of CaM from the cytosol to the nucleus was
      also examined after depolarization. Cells were depolarized and lysed and
      fractionated by centrifugation to determine the amount of CaM translocated to the
      nucleus. CaM was localized by immunocytochemistry and quantitated by Western
      blotting and imaging. Before and during KCl depolarization, cells were exposed to
      isoflurane, isoflurane plus Bay K 8644, nitrendipine, and omega-conotoxin GVIa,
      respectively. RESULTS: P-CREB increased after KCl depolarization. The increase of
      P-CREB peaked at depolarization duration of 30 s. The increase in P-CREB
      formation was inhibited by nitrendipine, but not omega-conotoxin, and by
      isoflurane in a concentration-dependent fashion. Pretreatment with the L-type
      Ca(2+) channel agonist, Bay K 8644, attenuated the inhibition of P-CREB formation
      by isoflurane. CaM presence in the nucleus occurred after KCl depolarization. CaM
      translocation was inhibited by nitrendipine and attenuated by isoflurane. Bay K
      8644 pretreatment decreased the isoflurane inhibition of CaM translocation to the
      nucleus. CONCLUSIONS: Our data demonstrate that isoflurane inhibits CaM
      translocation and P-CREB formation. This most likely occurs through isoflurane
      inhibition of Ca(2+)entry through L-type Ca(2+) channels.

PMID- 19762741
TI  - Monitoring with head-mounted displays: performance and safety in a full-scale
      simulator and part-task trainer.
AB  - BACKGROUND: Head-mounted displays (HMDs) can help anesthesiologists with
      intraoperative monitoring by keeping patients' vital signs within view at all
      times, even while the anesthesiologist is busy performing procedures or unable to
      see the monitor. The anesthesia literature suggests that there are advantages of
      HMD use, but research into head-up displays in the cockpit suggests that HMDs may
      exacerbate inattentional blindness (a tendency for users to miss unexpected but
      salient events in the field of view) and may introduce perceptual issues relating
      to focal depth. We investigated these issues in two simulator-based experiments.
      METHODS: Experiment 1 investigated whether wearing a HMD would affect how quickly
      anesthesiologists detect events, and whether the focus setting of the HMD (near
      or far) makes any difference. Twelve anesthesiologists provided anesthesia in
      three naturalistic scenarios within a simulated operating theater environment.
      There were 24 different events that occurred either on the patient monitor or in
      the operating room. Experiment 2 investigated whether anesthesiologists
      physically constrained by performing a procedure would detect patient-related
      events faster with a HMD than without. Twelve anesthesiologists performed a
      complex simulated clinical task on a part-task endoscopic dexterity trainer while
      monitoring the simulated patient's vital signs. All participants experienced four
      different events within each of two scenarios. RESULTS: Experiment 1 showed that
      neither wearing the HMD nor adjusting the focus setting reduced participants'
      ability to detect events (the number of events detected and time to detect
      events). In general, participants spent more time looking toward the patient and
      less time toward the anesthesia machine when they wore the HMD than when they
      used standard monitoring alone. Participants reported that they preferred the
      near focus setting. Experiment 2 showed that participants detected two of four
      events faster with the HMD, but one event more slowly with the HMD. Participants
      turned to look toward the anesthesia machine significantly less often when using
      the HMD. When using the HMD, participants reported that they were less busy,
      monitoring was easier, and they believed they were faster at detecting abnormal
      changes. CONCLUSIONS: The HMD helped anesthesiologists detect events when
      physically constrained, but not when physically unconstrained. Although there was
      no conclusive evidence of worsened inattentional blindness, found in aviation,
      the perceptual properties of the HMD display appear to influence whether events
      are detected. Anesthesiologists wearing HMDs should self-adjust the focus to
      minimize eyestrain and should be aware that some changes may not attract their
      attention. Future areas of research include developing principles for the design
      of HMDs, evaluating other types of HMDs, and evaluating the HMD in clinical
      contexts.

PMID- 19762742
TI  - Impact of multiaccess infusion devices on in vitro drug delivery during multi
      infusion therapy.
AB  - BACKGROUND: Multiaccess infusion sets allow multiple simultaneous infusions but
      may induce interference in drug delivery resulting from large variations in the
      delivery rate of potent drugs. In this study, we sought to understand the
      influence of multiaccess infusion device properties (dead space volume and
      antireflux valve [ARV]) on drug delivery during multi-infusion therapy. METHODS:
      Infusion sets differing in length, dead space volume, and presence of an ARV were
      assessed. Three drugs were infused simultaneously through different access
      points, and their concentrations were obtained using UV spectrophotometric
      analysis of the effluent. Different infusion configurations were compared by
      assessing (1) the amount of drug delivered to the patient per unit of time, (2)
      the mean amount of drug delivered to the patient per unit of time during the
      steady-state infusion (mass flow rate plateau), and (3) flow change efficiency
      calculated from the ratio of the area under the experimental instant mass flow
      rate curve to the area corresponding to theoretical instant mass flow rate curve.
      RESULTS: Infusion sets with lower dead space volumes offered significantly higher
      flow change efficiency (53.0% +/- 15.4% with a dead space volume equal to 0.046
      mL 5 min after the start of infusion) than infusion sets with higher dead space
      volume (5.6% +/- 8.2% with a dead space volume equal to 6.16 mL), whatever the
      flow rate changes. Even in case of large dead space volumes, the presence of an
      ARV significantly increased the mass flow rate plateau (from 92.4% to 99.3% of
      the theoretical plateau without and with the presence of an ARV, respectively).
      CONCLUSIONS: Multi-infusion therapy induces perturbation in drug delivery. These
      perturbations (lag time, backflow, and bolus) could be reduced by using infusion
      sets including very low dead space volume and an ARV.

PMID- 19762743
TI  - An analysis of drug delivery dynamics via a pediatric central venous infusion
      system: quantification of delays in achieving intended doses.
AB  - BACKGROUND: Pediatric patients frequently receive continuous infusions of drugs
      via central venous catheters in the intensive care unit and the operating room.
      This study characterized drug delivery profiles in a quantitative laboratory
      model of a standard pediatric central venous infusion system. METHODS: We
      evaluated drug delivery via a standard pediatric 8-cm, 4-F double-lumen catheter.
      One syringe pump infused normal saline as the carrier fluid through a limb of a Y
      piece connected to the catheter's 22-gauge distal lumen. Through the other limb
      of the Y-piece, a second syringe pump infused methylene blue, the model drug, at
      a constant rate of 0.5 mL/h. The volume delivered was collected every minute for
      quantitative analysis. We compared 2 mL/h and 12 mL/h total flow rates to mimic
      volume delivery to a 3-kg infant, and priming of the Y-piece with the model drug,
      to mimic resumption of a stopped drug infusion, versus no priming, to mimic a new
      infusion. Drug pump system start-up performance was measured to estimate this
      factor's contribution to infusion onset profiles. RESULTS: When initiating a new
      infusion of the model drug, the time to steady-state delivery at the catheter's
      end varied significantly among the studied scenarios as measured by the time to
      reach half of the targeted dose (t(50)). Onset of delivery with a low total flow
      was much slower (t(50) = 23.5 +/- 2.1 min) than with the high flow rate (t(50) =
      15.7 +/- 2.9 min). Priming the drug limb of the connecting Y-piece with methylene
      blue substantially shortened the time to steady state (low flow t(50) = 12.7 +/-
      0.6 min, high flow t(50) = 5.2 +/- 0.8 min). Time to cessation of drug delivery
      to the end of the catheter after stopping the drug pump was substantially shorter
      using the high carrier flow rate (t(50) = 3 +/- 0.5 min) compared with the low
      carrier flow rate (t(50) = 11.6 +/- 0.8 min). Drug pump system start-up
      performance contributed to onset delay. CONCLUSIONS: Current infusion techniques
      in the pediatric care setting can result in significant, unrecognized, and
      potentially hazardous delays in achieving delivery of intended drug doses to the
      patient. Total flow rate, priming of the infusion system, the dead volume of the
      fluid path, and the start-up performance of the infusion pump system contribute
      to delays in achieving targeted rates of drug delivery.

PMID- 19762744
TI  - Prevalence of malignant hyperthermia due to anesthesia in New York State, 2001
      2005.
AB  - BACKGROUND: Malignant hyperthermia (MH) is a pharmacogenetic syndrome that
      variably expresses itself on exposure to triggering agents. MH prevalence in the
      United States is not well documented. In this study, we assessed the prevalence
      of MH in New York State hospitals. METHODS: Using New York hospital discharge
      data for the years 2001 through 2005, we identified all patients with a diagnosis
      of MH due to anesthesia using International Classification of Diseases, Ninth
      Revision, Clinical Modification code 995.86. MH prevalence was evaluated by
      demographic and clinical characteristics. RESULTS: Of the 12,749,125 discharges
      from New York hospitals during the study period, 73 patients had a recorded
      diagnosis of MH due to anesthesia. Nearly three quarters of the MH patients were
      male and 71% were patients from emergency/urgent admissions. The estimated
      prevalence rate of MH was 0.96 (95% confidence interval [CI] 0.67-1.24) per
      100,000 surgical discharges and 1.08 (95% CI 0.75-1.41) per 100,000 discharges in
      which there was any indication of exposure to anesthesia. The estimated
      prevalence of MH for males was 2.5 to 4.5 times the rate for females. CONCLUSION:
      The prevalence of MH due to anesthesia in surgical patients treated in New York
      State hospitals is approximately 1 per 100,000. MH risk in males is significantly
      higher than in females.

PMID- 19762745
TI  - Core myopathies and risk of malignant hyperthermia.
AB  - In this article, we analyze myopathies with cores, for which an association to
      malignant hyperthermia (MH) has been suggested. We discuss the clinical features,
      the underlying genetic defects, subsequent effects on cellular calcium
      metabolism, and in vitro muscle responses to MH triggers. We describe in detail
      central core disease, multiminicore disease, and nemaline rod myopathy. We
      categorize the diseases according to the affected proteins and discuss the risk
      for MH, which is high or theoretically possible when the calcium-conducting
      proteins are affected.

PMID- 19762746
TI  - Epidemiology of anesthesia-related complications in labor and delivery, New York
      State, 2002-2005.
AB  - BACKGROUND: Epidemiologic data on anesthesia-related complications occurring
      during labor and delivery are essential for measuring and evaluating the safety
      and quality of obstetric anesthesia care but are lacking. We aimed to fill this
      research gap by exploring the epidemiologic patterns and risk factors of
      anesthesia-related complications in a large sample of women giving birth in New
      York hospitals. METHODS: Using the Healthcare Cost and Utilization Project State
      Inpatient Databases files, we identified all discharge records for labor and
      delivery from New York hospitals between 2002 and 2005. We then identified women
      who experienced any recorded anesthesia-related complication during labor and
      delivery as determined by International Classification of Diseases, Ninth
      Revision, Clinical Modification codes. The incidence of anesthesia-related
      complications was calculated by demographic and clinical characteristics.
      Multivariate logistic regression was performed to assess risk factors of
      anesthesia-related complications. RESULTS: Of the 957,471 deliveries studied,
      4438 (0.46%) had at least one anesthesia-related complication. The majority (55%)
      of anesthesia-related events occurring during labor and delivery were spinal
      complications, followed by systemic complications (43%) and overdose or adverse
      effects (2%). Multivariate logistic regression revealed five risk factors of
      anesthesia-related complications: cesarean delivery (odds ratio [OR] 2.51, 95%
      confidence interval [CI] 2.36-2.68), rural area (OR 1.33, 95% CI 1.21-1.46),
      Charlson-Deyo Comorbidity Index >or=1 (OR 1.47, 95% CI 1.28-1.69), Caucasian race
      (OR 1.37, 95% CI 1.24-1.52), and scheduled admission (OR 1.10, 95% CI 1.03-1.18).
      Anesthesia-related complications were associated with about a one-day increase in
      the average length of stay (3.89 +/- 3.69 [mean +/- SD] days vs 2.92 +/- 2.38
      days for deliveries without anesthesia-related complications, P < 0.0001) and a
      22-fold increased risk of maternal mortality (OR 22.26, 95% CI 11.20-44.24).
      CONCLUSION: The incidence of anesthesia-related complications during labor and
      delivery seems to be low but remains a cause of concern, particularly in women
      undergoing cesarean delivery, living in rural areas, or having preexisting
      medical conditions.

PMID- 19762747
TI  - Obstructive sleep apnea is not a risk factor for difficult intubation in morbidly
      obese patients.
AB  - BACKGROUND: Morbid obesity (MO), obstructive sleep apnea (OSA), and neck
      circumference (NC) are widely believed to be independent risk factors for
      difficult tracheal intubation. In this study, we sought to determine whether
      these factors were associated with increased risk of difficult intubation in
      patients undergoing bariatric surgery. The predictive factors tested were OSA and
      its severity, as determined by apnea-hypopnea index (AHI), gender, NC, and body
      mass index (BMI). METHODS: All sequentially enrolled MO patients underwent
      preoperative polysomnography. Severity of OSA was quantified using AHI and the
      American Society of Anesthesiologists' OSA severity scale. All patients had a
      standardized anesthetic that included positioning in the "ramped position" for
      direct laryngoscopy. RESULTS: One hundred eighty consecutive patients were
      recruited, 140 women and 40 men. The incidence of OSA was 68%. The mean BMI was
      49.4 kg/m(2). The mean AHI was 31.3 (range, 0-135). All the patients' tracheas
      were intubated successfully without the aid of rescue airways by anesthesiology
      residents. Six patients required three or more intubation attempts, a difficult
      intubation rate of 3.3%. There was an 8.3% incidence of difficult laryngoscopy,
      defined as a Cormack and Lehane Grade 3 or 4 view. There was no relationship
      between NC and difficult intubation (odds ratio 1.02, 95% confidence interval
      0.93-1.1), between the diagnosis of OSA and difficult intubation (P = 0.09), or
      between BMI and difficult intubation (odds ratio 0.99, 95% confidence interval
      0.92-1.06, P = 0.8). There was no relationship between number of intubation
      attempts and BMI (P = 0.8), AHI (P = 0.82), or NC (P = 0.3). Mallampati Grade III
      or more predicted difficult intubation (P = 0.02), as did male gender (P = 0.02).
      Finally, there was no relationship between Cormack and Lehane grade and BMI (P =
      0.88), AHI (P = 0.93), or OSA (P = 0.6). Increasing NC was associated with
      difficult laryngoscopy but not difficult intubation (P = 0.02). CONCLUSIONS: In
      MO patients undergoing bariatric surgery in the "ramped position," there was no
      relationship between the presence and severity of OSA, BMI, or NC and difficulty
      of intubation or laryngoscopy grade. Only a Mallampati score of 3 or 4 or male
      gender predicted difficult intubation.

PMID- 19762748
TI  - The relative exposure of the operating room staff to sevoflurane during
      intracerebral surgery.
AB  - BACKGROUND: Our primary aim in this study was to investigate whether escape of
      the volatile anesthetic sevoflurane from the surgical site during craniotomy for
      tumor resection increases the exposure of the neurosurgeon to the anesthetic when
      compared with the anesthesiologist. METHODS: Initially, the release of
      sevoflurane from the surgical site was measured during 35 tumorectomies starting
      from opening to closure of the dura. Volatile anesthetic absorbers were placed at
      three detection sites: 1) the surgeon's breathing zone, 2) the anesthesiologist's
      breathing zone, and 3) the farthest corner of the operation room. In the second
      sampling series that included 16 patients, the detector that had been in the
      corner of the operating room in the first series was now placed in the vicinity
      of the patient's mouth (within 5 cm). Sevoflurane captured by the absorbers was
      quantified by an independent chemist using chromatography. RESULTS: Absorbers in
      the surgeon's breathing zone (0.24 +/- 0.04 ppm) captured a significantly lower
      amount of sevoflurane compared with absorbers in the anesthesiologist's breathing
      zone (1.40 +/- 0.37 ppm) and comparable with that in the farthest corner of the
      operation room (0.25 +/- 0.07 ppm). There was no correlation between the amount
      of absorbed sevoflurane and the size of craniotomy window, even when adjusting
      for the variation in duration of surgery. In the second series of sampling,
      absorbers in the proximity of the patient's mouth captured the highest amount of
      sevoflurane (1.54 +/- 0.55 ppm), followed by the anesthesiologist's (1.14 +/-
      0.43 ppm) and the surgeon's (0.15 +/- 0.05 ppm) breathing zones. CONCLUSIONS: The
      close proximity of the surgeon's breathing zone to the craniotomy window does not
      appear to be a source of increased exposure to sevoflurane. The observed higher
      exposure of the anesthesiologist to sevoflurane in the operating room environment
      warrants further exploration.

PMID- 19762749
TI  - A prediction model for out-of-hospital cardiopulmonary resuscitation.
AB  - BACKGROUND: We created a prediction model to be used in cardiopulmonary
      resuscitation (CPR) attempts as a decision tool to omit futile CPR attempts and
      to save resources. METHODS: In this post hoc analysis, we assessed predictive
      parameters for neurological recovery after successful CPR. The original study was
      designed as a blinded, randomized, prospective, controlled, multicenter clinical
      trial. RESULTS: We identified 1166 prehospital cardiac arrest patients being
      treated with advanced cardiac life support. Seven hundred eighty-six of 1166
      patients (67.4%) died at the scene and 380 of 1166 (32.6%) were brought to the
      hospital. Two hundred sixty-five of 1166 patients (22.7%) died in the hospital.
      One hundred fifteen of 1166 (9.8%) were discharged from the hospital and 92 of
      the 115 patients (80%) could be followed-up. Good cerebral performance was
      regained by 54% of discharged patients (50 of 92 patients). In 46% of patients
      (42/92), unconsciousness or severe disability remained. Ventricular fibrillation
      was more likely to have occurred in patients with good neurological recovery
      (42/50 = 84.0%), whereas asystole was more likely in patients with poor
      neurological recovery (9/42 = 21.4%). A score was developed to predict the
      probability of death using logistic regression analysis. Predicting death in the
      hospital revealed a sensitivity of 99.8% (953/955), but only a specificity of
      2.9% (3/104; threshold 0.5). Predicting survival until discharge from the
      hospital revealed a sensitivity of 99% (103/104), but only a specificity of 8%
      (72/955; threshold 0.99). A receiver operating characteristic curve yielded an
      area under the curve of 0.795 (0.751-0.839) at a confidence interval of 95%.
      CONCLUSION: For out-of-hospital patients with cardiac arrest, parameters
      documented in the field did not allow accurate prediction of hospital survival.

PMID- 19762750
TI  - Positive end-expiratory pressure improves survival in a rodent model of
      cardiopulmonary resuscitation using high-dose epinephrine.
AB  - BACKGROUND: Multiple interventions have been tested in models of cardiopulmonary
      resuscitation (CPR) to optimize drug use, chest compressions, and ventilation.
      None has studied the effects of positive end-expiratory pressure (PEEP) on
      outcome. We hypothesized that because PEEP can reverse pulmonary atelectasis,
      lower pulmonary vascular resistance, and potentially improve cardiac output, its
      use during CPR would increase survival. METHODS: Anesthetized Sprague-Dawley rats
      were exposed to 1 min of asphyxial cardiac arrest. Resuscitation was standardized
      and consisted of chest compressions, oxygen (Fio(2) 1.0), and IV epinephrine 30
      microg/kg (Series 1) and 10 microg/kg (Series 2). Left ventricular function was
      assessed by echocardiography (Series 1), and animals were randomized to receive
      either 5 cm H(2)O PEEP or zero PEEP at commencement of CPR and throughout
      resuscitation. Survival was defined as the presence of a spontaneous circulation
      60 or 120 min (Series 2) after initial resuscitation. RESULTS: There were no
      baseline differences between the groups. In Series 1, administration of 5 cm
      H(2)O PEEP (Fio(2) 1.0 and 0.21) was associated with improved survival compared
      with zero PEEP (7/9 and 6/6 vs 0/9, P < 0.01 and <0.001, respectively).
      Application of 5 cm H(2)O PEEP (Fio(2) 1.0) increased left ventricular end
      diastolic area, systemic oxygenation, and functional residual capacity. Use of
      PEEP during CPR did not adversely affect left ventricular systolic function or
      arterial blood pressure. The outcome differences were not due to increased
      oxygenation because the rank order of survival was 5 cm H(2)O PEEP (Fio(2) 1.0)
      approximately 5 cm H(2)O PEEP (Fio(2) 0.21) > zero PEEP (Fio(2) 1.0), whereas the
      rank order of Pao(2) was 5 cm H(2)O PEEP (Fio(2) 1.0) > 5 cm H(2)O PEEP (Fio(2)
      0.21) approximately zero PEEP (Fio(2) 1.0). In an additional series in which
      epinephrine 10 microg/kg was used (Series 2), the survival was 100% with no
      beneficial effects of PEEP. CONCLUSION: In asphyxial cardiac arrest in a small
      rodent model, continuous application of PEEP (5 cm H(2)O) during and after CPR
      had beneficial effects on survival that were independent of oxygenation and
      without adverse cardiovascular effects.

PMID- 19762751
TI  - The effect of gender on compensatory neuromuscular response to upper airway
      obstruction in normal subjects under midazolam general anesthesia.
AB  - BACKGROUND: Upper airway patency may be compromised during sleep and anesthesia
      by either anatomical alterations (mechanical properties) or disturbances in the
      neural control (compensatory neuromuscular responses). The pathophysiology of
      upper airway obstruction during anesthesia may differ between men and women.
      Recently, we reported that the upper airway mechanical properties were comparable
      with those found during natural nonrapid eye movement sleep, as evaluated by
      measurements of passive critical closing pressure (P(CRIT)) and upstream
      resistance (R(US)) during midazolam sedation. In this study, we compared the
      effects of gender on compensatory neuromuscular responses to upper airway
      obstruction during midazolam general anesthesia. METHOD: Thirty-two subjects (14
      men and 18 women) were studied. We constructed pressure-flow relationships to
      evaluate P(CRIT) and R(US) during midazolam anesthesia. The midazolam anesthesia
      was induced with an initial dose of midazolam (0.07-0.08 mg/kg bolus) and
      maintained by midazolam infusion (0.3-0.4 microg x kg(-1) x min(-1)), and the
      level of anesthesia was assessed by Ramsay score (Level 5) and Observer's
      Assessment of Alertness/Sedation score (Level 2). Polysomnographic and
      hemodynamic variables were monitored while nasal pressure (via mask), inspiratory
      air flow (via pneumotachograph), and genioglossal electromyograph (EMG(GG)) were
      recorded. P(CRIT) was obtained in both the passive condition, under conditions of
      decreased EMG(GG) (passive P(CRIT)), and in an active condition, whereas EMG(GG)
      was increased (active P(CRIT)). The difference between the active P(CRIT) and
      passive P(CRIT) (Delta P(CRIT) (P - A)) was calculated in each subject to
      determine the compensatory neuromuscular response. RESULTS: The difference
      between the active P(CRIT) and passive P(CRIT) (Delta P(CRIT) (A - P)) was
      significantly greater in women than in men (4.6 +/- 2.8 cm H(2)O and 2.2 +/- 1.7
      cm H(2)O, respectively; P < 0.01), suggesting greater compensatory neuromuscular
      response to upper airway obstruction independent of arousal. CONCLUSION: We
      demonstrate that the arousal-independent compensatory neuromuscular responses to
      upper airway obstruction during midazolam anesthesia were partially maintained in
      women, and that gender may be a major determinant of the strength of compensatory
      responses during anesthesia.

PMID- 19762752
TI  - The effect of obesity on neuraxial technique difficulty in pregnant patients: a
      prospective, observational study.
AB  - BACKGROUND: Practitioners often presuppose that obesity will increase neuraxial
      technique difficulty in pregnant patients, but few investigators have
      systematically examined this population for risk factors associated with
      difficult epidural or spinal needle placement. We designed this study to
      prospectively identify factors that predict neuraxial technique difficulty in
      pregnant patients. METHODS: Using a prospective, observational format, pregnant
      patients were examined for multiple potential risk factors for neuraxial
      technique difficulty, including current body mass index, ability to palpate
      spinous processes, maximum back flexion, scoliosis, and experience of the
      practitioner. Neuraxial technique difficulty was then assessed using two
      measures: 1) the number of needle passes needed to reach the desired space, and
      2) the placement time from skin infiltration to either spinal injection or
      epidural catheter threading. Predictors of total needle passes were determined by
      fitting the data to a generalized linear model with negative binomial error.
      Predictors of neuraxial anesthetic time were determined by fitting a linear model
      to the log of neuraxial anesthetic placement time. A survival model was used to
      account for bias introduced when attending physicians intervened in resident
      physician procedures. RESULTS: Neuraxial procedures in 427 pregnant patients were
      studied. For both the number of needle passes and the neuraxial anesthetic
      placement time, the significant predictors of difficulty were the practitioner's
      ability to palpate the patient's bony landmarks and the patient's ability to flex
      her back. Obesity, as measured by body mass index, was not an independent
      predictor of either end point. Obesity did, however, strongly predict both the
      ability to palpate landmarks and flex the back. CONCLUSIONS: Despite concerns
      that obesity may cause difficulty with neuraxial technique, some obese patients
      have surprisingly easy neuraxial block placements. When approaching any neuraxial
      anesthetic in a pregnant patient, and especially in the obese parturient, back
      flexion and landmark palpation predict neuraxial technique difficulty.

PMID- 19762753
TI  - Modeling procedure and surgical times for current procedural terminology
      anesthesia-surgeon combinations and evaluation in terms of case-duration
      prediction and operating room efficiency: a multicenter study.
AB  - BACKGROUND: Gains in operating room (OR) scheduling may be obtained by using
      accurate statistical models to predict surgical and procedure times. The 3 main
      contributions of this article are the following: (i) the validation of Strum's
      results on the statistical distribution of case durations, including surgeon
      effects, using OR databases of 2 European hospitals, (ii) the use of expert prior
      expectations to predict durations of rarely observed cases, and (iii) the
      application of the proposed methods to predict case durations, with an analysis
      of the resulting increase in OR efficiency. METHODS: We retrospectively reviewed
      all recorded surgical cases of 2 large European teaching hospitals from 2005 to
      2008, involving 85,312 cases and 92,099 h in total. Surgical times tended to be
      skewed and bounded by some minimally required time. We compared the fit of the
      normal distribution with that of 2- and 3-parameter lognormal distributions for
      case durations of a range of Current Procedural Terminology (CPT)-anesthesia
      combinations, including possible surgeon effects. For cases with very few
      observations, we investigated whether supplementing the data information with
      surgeons' prior guesses helps to obtain better duration estimates. Finally, we
      used best fitting duration distributions to simulate the potential efficiency
      gains in OR scheduling. RESULTS: The 3-parameter lognormal distribution provides
      the best results for the case durations of CPT-anesthesia (surgeon) combinations,
      with an acceptable fit for almost 90% of the CPTs when segmented by the factor
      surgeon. The fit is best for surgical times and somewhat less for total procedure
      times. Surgeons' prior guesses are helpful for OR management to improve duration
      estimates of CPTs with very few (<10) observations. Compared with the standard
      way of case scheduling using the mean of the 3-parameter lognormal distribution
      for case scheduling reduces the mean overreserved OR time per case up to 11.9
      (11.8-12.0) min (55.6%) and the mean underreserved OR time per case up to 16.7
      (16.5-16.8) min (53.1%). When scheduling cases using the 4-parameter lognormal
      model the mean overutilized OR time is up to 20.0 (19.7-20.3) min per OR per day
      lower than for the standard method and 11.6 (11.3-12.0) min per OR per day lower
      as compared with the biased corrected mean. CONCLUSIONS: OR case scheduling can
      be improved by using the 3-parameter lognormal model with surgeon effects and by
      using surgeons' prior guesses for rarely observed CPTs. Using the 3-parameter
      lognormal model for case-duration prediction and scheduling significantly reduces
      both the prediction error and OR inefficiency.

PMID- 19762754
TI  - Forecasting and perception of average and latest hours worked by on-call
      anesthesiologists.
AB  - BACKGROUND: We studied the value of providing information to anesthesia providers
      about the length of time typically worked during on-call shifts. The mean time at
      which a shift ends can be used for purposes of trades, payments, or reverse
      auctions, because the mean is proportional to the total time. The 80th percentile
      (with a suitable upper confidence limit for uncertainty due to limited sample
      sizes) can be used for judging the earliest time by which after-work activities
      reasonably can be planned. METHODS: (A) Three years of operating room (OR)
      information system data were analyzed. Dependent variables were the earliest
      times when the numbers of ORs running were always <or=6 ORs, <or=4 ORs, and <or=2
      ORs. We progressively built linear regression models for each of the three
      dependent variables using day of the week, scheduled number of cases, scheduled
      hours of cases (including turnovers), and linear time trend. Calculations were
      repeated after excluding residuals. Calculations were repeated using regression
      trees. (B) Anesthesiologists were surveyed about their perceptions of the mean
      and 80th percentiles. RESULTS: (A) For the three thresholds and two end points
      (mean and 80th percentile), differences among days of the week were as large as
      45 min. Differences between end points for the same weekdays were as large as 245
      min. Comparatively, additional knowledge about the number or hours of cases
      provided in the late afternoon on the working day before surgery reduced the mean
      absolute error by only 4.1-6.0 min. Results were insensitive to a variety of
      analytic methods. Information available more days before the day of surgery
      (e.g., 1 wk) would have had even less incremental predictive value. (B) The mean
      absolute error of anesthesiologists' estimates for 80th percentiles was 60 min,
      principally because of underestimation of the 80th percentiles. More than half
      (69%, P = 0.0003) of anesthesiologists' estimates for 80th percentiles had error
      >30 min, whereas errors of this magnitude were less for the mean (44%, P =
      0.0004). CONCLUSIONS: Historical data from OR or anesthesia information
      management systems, or from anesthesia billing systems, can be used months before
      staff scheduling to provide insight to anesthesia providers on respective calls.
      The data are useful because experience provides limited intuition. Updates on
      scheduled workload available closer to the day of surgery provided only marginal
      increases in knowledge over the use of historical data.

PMID- 19762755
TI  - The electrocortical effects of enflurane: experiment and theory.
AB  - BACKGROUND: High concentrations of enflurane will induce a characteristic
      electroencephalogram pattern consisting of periods of suppression alternating
      with large short paroxysmal epileptiform discharges (PEDs). In this study, we
      compared a theoretical computer model of this activity with real local field
      potential (LFP) data obtained from anesthetized rats. METHODS: After implantation
      of a high-density 8 x 8 electrode array in the visual cortex, the patterns of LFP
      and multiunit spike activity were recorded in rats during 0.5, 1.0, 1.5, and 2.0
      minimum alveolar anesthetic concentration (MAC) enflurane anesthesia. These
      recordings were compared with computer simulations from a mean field model of
      neocortical dynamics. The neuronal effect of increasing enflurane concentration
      was simulated by prolonging the decay time constant of the inhibitory
      postsynaptic potential (IPSP). The amplitude of the excitatory postsynaptic
      potential (EPSP) was modulated, inverse to the neocortical firing rate. RESULTS:
      In the anesthetized rats, increasing enflurane concentrations consistently caused
      the appearance of suppression pattern (>1.5 MAC) in the LFP recordings. The mean
      rate of multiunit spike activity decreased from 2.54/s (0.5 MAC) to 0.19/s (2.0
      MAC). At high MAC, the majority of the multiunit action potential events became
      synchronous with the PED. In the theoretical model, prolongation of the IPSP
      decay time and activity-dependent EPSP modulation resulted in output that was
      similar in morphology to that obtained from the experimental data. The propensity
      for rhythmic seizure-like activity in the model could be determined by analysis
      of the eigenvalues of the equations. CONCLUSION: It is possible to use a mean
      field theory of neocortical dynamics to replicate the PED pattern observed in
      LFPs in rats under enflurane anesthesia. This pattern requires a combination of a
      moderately increased total area under the IPSP, prolonged IPSP decay time, and
      also activity-dependent modulation of EPSP amplitude.

PMID- 19762756
TI  - Sevoflurane preconditioning induces rapid ischemic tolerance against spinal cord
      ischemia/reperfusion through activation of extracellular signal-regulated kinase
      in rabbits.
AB  - BACKGROUND: The protective effect of sevoflurane preconditioning against spinal
      cord ischemia/reperfusion (I/R) is unclear. We designed this study to investigate
      whether sevoflurane preconditioning could induce rapid ischemic tolerance to the
      spinal cord in a rabbit model of transient spinal cord ischemia and how the role
      of extracellular signal-regulated kinase (ERK) is involved. METHODS: To test
      whether preconditioning with sevoflurane induces rapid ischemic tolerance, New
      Zealand White male rabbits were randomly assigned to three groups. Animals in the
      Sev group received preconditioning with 3.7% sevoflurane (1.0 minimum alveolar
      anesthetic concentration) in 96% oxygen for 30 min, whereas animals in the O(2)
      group serving as controls inhaled only 96% oxygen for 30 min. The Sham group
      received the same anesthesia and surgical preparation but no preconditioning or
      spinal cord I/R. To evaluate the role of ERK activation in sevoflurane
      preconditioning, rabbits were randomly assigned to four groups. U0126, an ERK
      inhibitor, was administered IV 20 min before the beginning of preconditioning in
      the U0126 + O(2) and U0126 + Sev groups. Dimethylsulfoxide was administered IV at
      the same time in the vehicle + O(2) and vehicle + Sev groups. At 1 h after
      preconditioning, the animals were subjected to spinal cord I/R induced by
      infrarenal aorta occlusion. All animals were assessed at 48 h after reperfusion
      with modified Tarlov criteria, and the spinal cord segments (L5) were harvested
      for histopathological examination, TUNEL staining, and Western blot of phosphor
      ERK1/2. RESULTS: The animals in the Sev group had higher neurological scores and
      more normal motor neurons than those in the O(2) group (P < 0.01 for each
      comparison). Compared with vehicle + Sev group, the U0126 + Sev group had worse
      neurological outcomes, fewer viable neurons, more apoptotic neurons, and
      significantly decreased ERK1/2 phosphorylation (P <or= 0.01 for each comparison).
      There were no significant differences in the outcomes among vehicle + O(2), U0126
      + O(2), and U0126 + Sev groups. CONCLUSIONS: This study demonstrates that
      sevoflurane preconditioning induces rapid tolerance to spinal cord I/R in
      rabbits, and the tolerance is possibly mediated through the activation of ERK.
      These data suggest that sevoflurane preconditioning might provide a new practical
      method for protecting perioperative spinal cord I/R.

PMID- 19762757
TI  - Novel variants near the central domain of RYR1 in two malignant hyperthermia
      susceptible families from Taiwan.
AB  - BACKGROUND: Our primary objective was to detect malignant hyperthermia (MH)
      susceptible persons and thereby prevent MH episodes. We identified variants in
      the ryanodine receptor isoform 1 using molecular pedigree analysis. METHODS:
      Nineteen exons covering major hotspots were chosen for the primary screening by
      polymerase chain reaction, denaturing high performance liquid chromatography, and
      confirmed by direct sequencing. RESULTS: Three novel variants involving amino
      acid changes were identified in two unrelated families as Met2698Arg, Glu2724Lys
      in exon 51 and Leu2785Val in exon 53. CONCLUSIONS: Three novel ryanodine receptor
      isoform 1 variants located either near or within the central domain might
      predispose carriers to MH.

PMID- 19762758
TI  - A comparison of intravenous oxycodone and intravenous morphine in patient
      controlled postoperative analgesia after laparoscopic hysterectomy.
AB  - INTRODUCTION: In this study, we investigated the dose requirements, pain relief,
      and side effects of oxycodone versus morphine after surgery with visceral pain.
      METHODS: Ninety-one women received IV oxycodone or morphine before the end of
      laparoscopic hysterectomy and then continued with patient-controlled analgesia
      for 24 h postoperatively. RESULTS: The accumulated oxycodone consumption was less
      (13.3 +/- 10.4 mg vs 22.0 +/- 13.1 mg, P = 0.001) than morphine. With oxycodone,
      the visual analog scale scores were significantly lower in the first hour
      postoperatively and sedation was less during the 24-h postoperative period, P =
      0.006. CONCLUSIONS: Oxycodone was more potent than morphine for visceral pain
      relief but not for sedation.

PMID- 19762759
TI  - Complete Freund's adjuvant-induced intervertebral discitis as an animal model for
      discogenic low back pain.
AB  - BACKGROUND: Although numerous animal models for low back pain associated with
      intervertebral disk (IVD) degeneration have been proposed, insufficient data have
      been provided to make any conclusions regarding pain. Our aim in this study was
      to determine the reliability of complete Freund's adjuvant (CFA) injection into
      the rat spine as an animal model representing human discogenic pain. METHODS: We
      studied IVD degenerative changes with pain development after a 10-microL CFA
      injection into the L5-6 IVD of adult rats using behavioral, histologic, and
      biochemical studies. Serial histologic changes were analyzed to detect
      degenerative changes. Expression of calcitonin gene-related peptide (CGRP),
      prostaglandin E (PGE), and inducible nitric oxide synthase (iNOS) were determined
      using immunohistochemistry or real-time polymerase chain reaction as support data
      for pain development. In addition, CGRP immunoreactivity (ir) at the IVD was
      considered indirect evidence of neural ingrowth into the IVD. RESULTS: There was
      a significant increase of the hindpaw withdrawal response in the CFA group until
      7 wk postoperatively (P < 0.05). Histologic analyses revealed progressive
      degenerative changes of the disks without any damage in adjacent structures,
      including nerve roots. In the CGRP-ir staining study, the bilateral dorsal horns
      and IVD had positive ir after intradiscal CFA injection. CGRP mRNA expression was
      increased in the dorsal root ganglion (DRG) at 2 and 4 wk, whereas PGE and iNOS
      mRNAs were markedly increased at 2 wk. The increment of CGRP expression was
      higher in allodynic rats compared with nonallodynic rats. CONCLUSION: Intradiscal
      CFA injection led to chronic disk degeneration with allodynia, which was
      suggested by pain behavior and expression of pain-related mediators. The
      increment of CGRP, PGE, and iNOS also suggest pain-related signal processing
      between the IVD and the neural pathway in this animal model. This animal model
      may be useful for future research related to the pathophysiology and development
      of novel treatment for spine-related pain.

PMID- 19762760
TI  - The peripheral antinociceptive effects of endomorphin-1 and kynurenic acid in the
      rat inflamed joint model.
AB  - BACKGROUND: Several data suggest that both opioid and N-methyl-d-aspartate (NMDA)
      receptors are localized at the peripheral level, and drugs acting on these
      receptors may produce antinociception after topical administration; however, the
      antinociceptive effect of endogenous ligands at these receptors is poorly
      clarified. Our goal in this study was to determine the antinociceptive potency of
      the endogenous opioid peptide, endomorphin-1 (EM1), and the endogenous NMDA
      receptor antagonist, kynurenic acid (KYNA), and their interaction at the
      peripheral level in the rat inflamed joint model. METHODS: Mechanical
      hypersensitivity was produced by injection of carrageenan (300 microg/20 microL)
      into the tibiotarsal joint of the right hind leg. The mechanical pain threshold
      was assessed by von Frey filaments (0.064-110 g). EM1 (30, 100, and 200 microg),
      KYNA (30, 100, 200, and 400 microg), and their combinations in a fixed-dose ratio
      (1:1) were injected into the inflamed joint, and the pain threshold was
      determined repeatedly for 75 min after the drug administrations. RESULTS: Neither
      EM1 nor KYNA administered to the inflamed joint influenced the pain threshold at
      the noninflamed side. Both ligands produced dose-dependent antihyperalgesia, and
      the highest doses caused a prolonged effect. EM1 had higher potency (30%
      effective dose [ED(30)] and 50% effective dose [ED(50)] values were 112 microg
      [confidence interval {CI}: 80-146] and 167 microg [CI: 135-220], respectively)
      compared with KYNA (ED(30) and ED(50) values were 204 microg [CI: 160-251] and
      330 microg [CI: 280-407], respectively). The antinociceptive effect of EM1 was
      prevented by subcutaneous naltrexone pretreatment. The coadministration of EM1
      with KYNA caused an enhanced and/or prolonged antinociceptive effect. The ED(30)
      and ED(50) values of the combination were 141 microg [CI: 83-182] and 231 microg
      [CI: 190-293], respectively, which did not differ significantly from the
      theoretically additive values (ED(30) and ED(50) values were 145 microg [CI: 68
      237] and 220 microg [CI: 144-230], respectively), thus the interaction between
      these ligands is additive. None of the treatments caused any sign of side
      effects. CONCLUSION: Peripherally administered endogenous opioid agonist and NMDA
      receptor antagonist ligands might be beneficial in inflammatory pain. Because
      both drugs barely cross the blood-brain barrier, their local administration
      causes no central side effects.

PMID- 19762761
TI  - Activation of extracellular signal-regulated kinase in sciatic nerve contributes
      to neuropathic pain after partial sciatic nerve ligation in mice.
AB  - BACKGROUND: The mitogen-activated protein kinase family plays an important role
      in several types of pain. However, the detailed role of phosphorylated
      extracellular signal-regulated kinase (pERK) in the region of injured peripheral
      nerve is poorly understood. In this study, we investigated whether pERK in
      injured sciatic nerve contributes to neuropathic pain induced by partial sciatic
      nerve ligation (PSL) in mice. METHODS: Mice received PSL; pERK1/2 (p44/42) in
      sciatic nerve was measured by both Western blotting and immunohistochemistry.
      U0126 (an ERK kinase inhibitor) was injected twice, an intraneural injection (20
      nmol/2 microL) 30 min before PSL, and a perineural injection (20 nmol/10 microL)
      on Day 1 after PSL. Thermal hyperalgesia and tactile allodynia induced by PSL
      were evaluated by the thermal paw withdrawal test and the von Frey test,
      respectively. RESULTS: As measured by Western blotting, in sham-operated mice,
      the levels of pERK1/2 in sciatic nerve were constant and the same as those in
      naive mice across Days 1-14. In PSL-operated mice, a significant increase in
      pERK1/2 was observed on Day 1 after PSL and persisted until Day 3. As measured by
      immunohistochemistry, immunoreactivity of pERK1/2 in PSL-operated sciatic nerve
      was markedly increased in comparison with that in sham-operated sciatic nerve on
      Day 1 after PSL. In the sciatic nerve on Day 1 after PSL, as indicated by double
      immunostaining, the increased immunoreactivity of pERK1/2 was colocalized with
      glial fibrillary acidic protein (GFAP), a marker of Schwann cells, but not F4/80,
      a marker of macrophages. PSL-induced thermal hyperalgesia was significantly
      attenuated by treatment with U0126 on Days 3, 7, and 14 after PSL. The PSL
      induced tactile allodynia was also significantly attenuated by treatment with
      U0126 on Days 7 and 14 after PSL. CONCLUSION: Activation of ERK in Schwann cells
      of the injured peripheral nervous system may play an important role in the
      development of neuropathic pain. Our results suggest that pERK itself and ERK
      related mediators are potential therapeutic targets for the treatment of
      neuropathic pain.

PMID- 19762762
TI  - The synergistic interaction between morphine and maprotiline after intrathecal
      injection in rats.
AB  - BACKGROUND: Antidepressant drugs act as potent inhibitors of norepinephrine
      and/or serotonin reuptake and are widely used with opioids for the treatment of
      chronic pain. The mechanism of this increased analgesic action is unclear. We
      compared the antinociceptive effects of the intrathecal administration of
      morphine with that of a nonselective (amitriptyline) or selective (maprotiline or
      citalopram) antidepressant drug using the thermal withdrawal test in rats. We
      also investigated the possible mechanisms involved in the interactions of these
      drugs. METHODS: Male Wistar rats were anesthetized with sevoflurane and
      administered morphine and antidepressant drugs, or saline, through intrathecal
      injection. The antinociceptive effect was evaluated using the thermal withdrawal
      test before and after drug administration. The time for the withdrawal reaction
      was expressed as percentage of maximum possible effect (MPE). Animals were also
      pretreated with yohimbine (a nonselective alpha2-adrenergic antagonist) and
      naloxone (a nonselective opioid antagonist) for mechanism of action studies.
      Pharmacologic interaction was evaluated using isobolographic analysis of
      simultaneous administration of fixed proportions of maprotiline and morphine.
      RESULTS: Single intrathecal administration of morphine (2 microg), amitriptiline
      (125 microg), citalopram (144 microg), and maprotiline (1.25 microg) produced
      51.6% +/- 8.9%, 10.3% +/- 3.2%, 33.8% +/- 5.2%, and 48.5% +/- 9.2% MPE,
      respectively. The antinociceptive effect of morphine was increased when combined
      with amitriptyline (91.3% +/- 4.6% MPE) and maprotiline (86.9% +/- 9.2% MPE) but
      not with citalopram (40.6% +/- 4.6% MPE). Coadministration of maprotiline
      increased the antinociceptive duration of morphine by 4-fold (from 120 to 480
      min), which was reversed by pretreatment with the alpha-2 adrenoceptor inhibitor,
      yohimbine, and the mu-type opioid receptor antagonist, naloxone. Isobolographic
      analysis demonstrated a synergistic interaction between morphine and maprotiline.
      CONCLUSIONS: Selective norepinephrine reuptake inhibitors can significantly
      increase the intensity and duration of morphine antinociceptive activity via both
      alpha(2)-adrenergic and opioid receptors. This interaction was not observed with
      the selective serotonin inhibitor, citalopram.

PMID- 19762763
TI  - Licking decreases phosphorylation of extracellular signal-regulated kinase in the
      dorsal horn of the spinal cord after a formalin test.
AB  - BACKGROUND: Nociceptive behaviors might attenuate pain sensation. Phosphorylation
      of extracellular signal-regulated kinase (pERK) was recently reported to be
      induced by noxious stimuli in dorsal horn neurons. We investigated, in a formalin
      test, whether pERK of the dorsal horn is affected by licking. METHODS: Twenty
      four adult male rats were divided into four groups: control, formalin test,
      restricted control, and restricted formalin test. Ten percent formalin was
      injected subcutaneously into the left rear paw of the formalin test and
      restricted formalin test groups. The control and formalin test group rats were
      kept in a clear plastic chamber, whereas the restricted control and restricted
      formalin test group rats were kept in a modified-restraint, pipe-shaped chamber.
      All rats were killed after 25 min. Twelve sections of the lumbar spinal cord were
      processed for p-ERK immunohistochemistry using the avidin-biotin peroxidase
      method. RESULTS: The number of p-ERK positive cells in the restricted formalin
      test group was significantly higher than in the other three groups in the
      ipsilateral-side superficial dorsal horn (P < 0.05). However, there was no
      significant difference between the formalin test group and the two control groups
      in pERK expression. CONCLUSION: Licking decreased pERK of the spinal cord of the
      formalin test group. The findings suggested that licking attenuated the pain of
      the formalin test.

PMID- 19762764
TI  - Lipid emulsion improves recovery from bupivacaine-induced cardiac arrest, but not
      from ropivacaine- or mepivacaine-induced cardiac arrest.
AB  - BACKGROUND: Cardiac toxicity significantly correlates with the lipophilicity of
      local anesthetics (LAs). Recently, the infusion of lipid emulsions has been shown
      to be a promising approach to treat LA-induced cardiac arrest. As the postulated
      mechanism of action, the so-called "lipid sink" effect may depend on the
      lipophilicity of LAs. In this study, we investigated whether lipid effects differ
      with regard to the administered LAs. METHODS: In the isolated rat heart, cardiac
      arrest was induced by administration of equipotent doses of bupivacaine,
      ropivacaine, and mepivacaine, respectively, followed by cardiac perfusion with or
      without lipid emulsion (0.25 mL x kg(-1) x min(-1)). Subsequently, the times from
      the start of perfusion to return of first heart activity and to recovery of heart
      rate and rate-pressure product (to 90% of baseline values) were assessed.
      RESULTS: In all groups, lipid infusion had no effects on the time to the return
      of any cardiac activity. However, recovery times of heart rate and rate-pressure
      product (to 90% of baseline values) were significantly shorter with the
      administration of lipids in bupivacaine-induced cardiac toxicity, but not in
      ropivacaine- or mepivacaine-induced cardiac toxicity. CONCLUSIONS: These data
      show that the effects of lipid infusion on LA-induced cardiac arrest are strongly
      dependent on the administered LAs itself. We conclude that lipophilicity of LAs
      has a marked impact on the efficacy of lipid infusions to treat cardiac arrest
      induced by these drugs.

PMID- 19762765
TI  - The analgesic effect of paracetamol when added to lidocaine for intravenous
      regional anesthesia.
AB  - BACKGROUND: In this study, we evaluated the effect of paracetamol on sensory and
      motor block onset time, tourniquet pain, and postoperative analgesia, when added
      to lidocaine in IV regional anesthesia (IVRA). METHODS: Sixty patients undergoing
      hand surgery were randomly and blindly divided into three groups. All groups
      received IVRA lidocaine (3 mg/kg) diluted with saline to a total volume of 40 mL.
      Group 1 received IVRA lidocaine plus IV saline, Group 2 received IVRA lidocaine
      and paracetamol (300 mg) admixture plus IV saline, and Group 3 received IVRA
      lidocaine plus IV paracetamol (300 mg). Sensory and motor block onset time,
      tourniquet pain, and analgesic use were assessed during operation. After
      tourniquet deflation, visual analog scale (VAS) scores at 1, 2, 4, 6, 12, and 24
      h, the time to first analgesic requirement, total analgesic consumption in first
      24 h, and side effects were noted. RESULTS: Onset of motor block was shorter and
      recovery of motor and sensory block was significantly longer in Group 2 (P <
      0.05). Intraoperative VAS scores at intraoperative 20, 30, and 40 min were
      significantly lower in Group 2 (P < 0.05). Intraoperative fentanyl consumption
      (78 +/- 12, 58 +/- 14, 78 +/- 11 microg, respectively) and the number of patients
      who required fentanyl for tourniquet pain (13 patients, 3 patients, 9 patients,
      respectively) were significantly less in Group 2 (P < 0.05). Time to
      postoperative fentanyl administration was also prolonged (15 +/- 6, 25 +/- 5, 15
      +/- 4 min, respectively) in Group 2 (P < 0.05). The quality of surgical
      anesthesia was better in Group 2 (P < 0.05). Postoperative VAS scores and time of
      initial analgesic requirement were similar among groups; however, the total
      amount of diclophenac use was less in Group 2 (P < 0.05). CONCLUSION: The
      addition of paracetamol during IVRA with lidocaine decreased tourniquet pain,
      increased anesthesia quality, and decreased postoperative analgesic consumption.

PMID- 19762766
TI  - The median effective dose of bupivacaine, levobupivacaine, and ropivacaine after
      intrathecal injection in lower limb surgery.
AB  - BACKGROUND: Intrathecal anesthesia is commonly used for lower limb surgery.
      Bupivacaine, levobupivacaine, and ropivacaine have all been used as intrathecal
      drugs, but their relative potency in this context has not been fully determined.
      In this study, we determined the median effective dose (ED(50)) of these three
      local anesthetics for intrathecal anesthesia in lower limb surgery and hence
      their relative potencies. METHODS: Seventy-five patients scheduled for lower limb
      surgery under combined spinal-epidural anesthesia were randomly allocated to one
      of three groups receiving intrathecal bupivacaine, levobupivacaine, or
      ropivacaine. The dose of local anesthetic was varied using up-down sequential
      allocation technique. The dose for the first patient in each group was 8 mg, and
      the dosing increment was set at 1 mg. Subsequent doses in each group were
      determined by the outcome in the previous patient using success or failure of the
      spinal anesthesia as the primary end point. A success was recorded if a bilateral
      T12 sensory block to cold was attained within 20 min after intrathecal injection,
      and the surgery proceeded successfully until at least 50 min after the
      intrathecal injection without supplementary epidural injection. The ED(50) was
      calculated using the method of Dixon and Massey. RESULTS: The ED(50)s were 5.50
      mg for bupivacaine (95% confidence interval [CI]: 4.90-6.10 mg), 5.68 mg for
      levobupivacaine (95% CI: 4.92-6.44 mg), and 8.41 mg for ropivacaine (95% CI: 7.15
      9.67 mg) in intrathecal anesthesia. The relative anesthetic potency ratios are
      0.97 (95% CI: 0.81-1.17) for levobupivacaine/bupivacaine, 0.65 (95% CI: 0.54
      0.80) for ropivacaine/bupivacaine, and 0.68 (95% CI: 0.55-0.84) for
      ropivacaine/levobupivacaine. CONCLUSION: This study suggests that in intrathecal
      anesthesia for lower limb surgery, ropivacaine is less potent than
      levobupivacaine and bupivacaine, whereas the potency is similar between
      levobupivacaine and bupivacaine.

PMID- 19762767
TI  - Fractal cardiovascular dynamics and baroreflex sensitivity after stellate
      ganglion block.
AB  - BACKGROUND: It has been shown that stellate ganglion block can attenuate
      baroreflex sensitivity. Our primary purpose in this study was to determine
      whether fractal dynamics (dynamic change of self-similar fluctuation patterns) of
      not only heart rate but also systolic blood pressure variability are involved in
      attenuation of baroreflex sensitivity after stellate ganglion block. METHODS:
      Sixteen young, healthy volunteers entered the study. Spectral analysis of heart
      rate and systolic blood pressure variability was performed before and 30, 60, 90,
      and 120 min after either right or left stellate ganglion block, separated by a 1
      to 1(1/2)-mo interval, with 6 mL of 1% mepivacaine. Shortly after each spectral
      analysis, baroreflex sensitivity was assessed with the head-up tilt test.
      RESULTS: Baroreflex sensitivity, assessed by the head-up tilt test, was
      significantly attenuated at 30 min after either right or left stellate ganglion
      block (1.26 +/- 0.18 to 0.46 +/- 0.08 bpm/mm Hg, P < 0.05 and 1.17 +/- 0.35 to
      0.51 +/- 0.13 bpm/min, P < 0.01, respectively). Fractal slopes reflecting the
      degree of self-similarity of fluctuations were significantly increased at 30 min
      after either right or left stellate ganglion block (right stellate ganglion block
      -heart rate; -1.08 +/- 0.30 to -1.62 +/- 0.22, P < 0.01; right stellate ganglion
      block--systolic blood pressure; -1.30 +/- 0.80 to -2.40 +/- 0.80, P < 0.05; left
      stellate ganglion block--systolic blood pressure; -1.20 +/- 0.40 to -2.13 +/-
      0.50, P < 0.05). Fractal slope did not change after left stellate ganglion block
      with heart rate variability analysis. CONCLUSIONS: Loss of complexity (status of
      being complex behavior) of both heart rate and systolic blood pressure
      variability, indicated by increased fractal slopes, is one mechanism in
      attenuating baroreflex sensitivity after stellate ganglion block.

PMID- 19762768
TI  - Is there evidence for improved maternal satisfaction with patient-controlled
      epidural anesthesia?

PMID- 19762769
TI  - Hydroxyethyl starch 130/0.4: does "modern" mean safe?

PMID- 19762770
TI  - Modern starches are not safer than old ones.

PMID- 19762771
TI  - Continuous infraclavicular plexus blockade.

PMID- 19762772
TI  - Blind enough? Sham subtenon block in pediatric patients.

PMID- 19762773
TI  - Unusual cause of leak in Datex Aisys.

PMID- 19762774
TI  - A novel mechanism causing bradycardia during right lung pleurodesis.

PMID- 19762775
TI  - Aspiration risk after esophagectomy.

PMID- 19762778
TI  - Absence of Akt1 reduces vascular smooth muscle cell migration and survival and
      induces features of plaque vulnerability and cardiac dysfunction during
      atherosclerosis.
AB  - OBJECTIVE: Deletion of Akt1 leads to severe atherosclerosis and occlusive
      coronary artery disease. Vascular smooth muscle cells (VSMCs) are an important
      component of atherosclerotic plaques, responsible for promoting plaque stability
      in advanced lesions. Fibrous caps of unstable plaques contain less collagen and
      ECM components and fewer VSMCs than caps from stable lesions. Here, we
      investigated the role of Akt1 in VSMC proliferation, migration, and oxidative
      stress-induced apoptosis. In addition, we also characterized the atherosclerotic
      plaque morphology and cardiac function in an atherosclerosis-prone mouse model
      deficient in Akt1. METHODS AND RESULTS: Absence of Akt1 reduces VSMC
      proliferation and migration. Mechanistically, the proliferation and migratory
      phenotype found in Akt1-null VSMCs was linked to reduced Rac-1 activity and MMP-2
      secretion. Serum starvation and stress-induced apoptosis was enhanced in Akt1
      null VSMCs as determined by flow cytometry using Annexin V/PI staining.
      Immunohistochemical analysis of atherosclerotic plaques from Akt1(-/-ApoE-/-)
      mice showed a dramatic increase in plaque vulnerability characteristics such as
      enlarged necrotic core and reduced fibrous cap and collagen content. Finally, we
      show evidence of myocardial infarcts and cardiac dysfunction in Akt1(-/-ApoE-/-)
      mice analyzed by immunohistochemistry and echocardiography, respectively.
      CONCLUSIONS: Akt1 is essential for VSMC proliferation, migration, and protection
      against oxidative stress-induced apoptosis. Absence of Akt1 induces features of
      plaque vulnerability and cardiac dysfunction in a mouse model of atherosclerosis.

PMID- 19762779
TI  - Inhibition of prolyl hydroxylase domain-containing protein suppressed
      lipopolysaccharide-induced TNF-alpha expression.
AB  - OBJECTIVE: Prolyl hydroxylase domain-containing proteins (PHDs) play pivotal
      roles in oxygen-sensing system through the regulation of alpha-subunit of hypoxia
      inducible factor (HIF), a key transcription factor governing a large set of gene
      expression to adapt hypoxia. Although tissue hypoxia plays an essential role in
      maintaining inflammation, the role of PHDs in the inflammatory responses has not
      been clearly determined. Here, we investigated the role of PHDs in
      lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-alpha)
      induction in macrophages. METHODS AND RESULTS: Northern blot analysis and ELISA
      revealed that LPS-induced TNF-alpha upregulation was strongly suppressed by PHD
      inhibitors, dimethyloxallyl glycine (DMOG), and TM6008 in RAW264.7 macrophages.
      DMOG suppressed LPS-induced TNF-alpha upregulation in HIF-1alpha-depleted cells
      and HIF-1alpha overexpression failed to suppress the induction of TNF-alpha. DMOG
      rather suppressed LPS-induced NF-kappaB transcriptional activity. Downregulation
      of Phd1 or Phd2 mRNA by RNA interference partially attenuated LPS-induced TNF
      alpha induction. DMOG also inhibited LPS-induced TNF-alpha production in
      peritoneal macrophages as well as human macrophages. CONCLUSIONS: PHD inhibition
      by DMOG or RNA interference inhibited LPS-induced TNF-alpha upregulation in
      macrophages possibly through NF-kappaB inhibition, which is independent of HIF
      1alpha accumulation. This study suggests that PHDs are positive regulators of LPS
      induced inflammatory process, and therefore inhibition of PHD may be a novel
      strategy for the treatment of inflammatory diseases.

PMID- 19762780
TI  - Fn14-Fc fusion protein regulates atherosclerosis in ApoE-/- mice and inhibits
      macrophage lipid uptake in vitro.
AB  - OBJECTIVE: TWEAK is a multifunctional cytokine belonging to the tumor necrosis
      factor superfamily and binds to the receptor Fn14. TWEAK and Fn14 are expressed
      in atherosclerotic plaques in areas rich in macrophages and foam cells. We
      investigated the role of TWEAK/Fn14 interactions in ApoE(-/-) mice and bone
      marrow-derived macrophages in vitro. METHODS AND RESULTS: ApoE(-/-) mice were
      treated with TWEAK-inhibiting fusion protein, Fn14-Fc, in an early (5 to 17 weeks
      of age) or delayed (17 to 29 weeks of age) setting. In the aortic arch, Fn14-Fc
      as compared to control treatment resulted in advanced plaques which were smaller
      (early treatment), fewer (delayed treatment), lower in fibrotic content (early
      and delayed treatment), and exhibited an increased macrophage content and smaller
      macrophage size (delayed treatment). There were no differences in apoptosis in
      atherosclerotic plaques after Fn14-Fc versus control Ab treatment. However,
      blocking TWEAK resulted in less macrophage uptake of modified lipids in vitro.
      CONCLUSIONS: Fn14-Fc fusion protein treatment did not prevent lesion initiation
      but inhibited some features of plaque progression and induced a unique advanced
      plaque phenotype with increased macrophage content and smaller macrophage size,
      which may be attributable to reduced lipid uptake. These findings indicate that
      TWEAK/Fn14 interactions regulate atherosclerosis and mediate lipid uptake in
      macrophages.

PMID- 19762781
TI  - Matrix metalloproteinase-10 is upregulated by thrombin in endothelial cells and
      increased in patients with enhanced thrombin generation.
AB  - OBJECTIVE: Thrombin is a multifunctional serine protease that promotes vascular
      proinflammatory responses whose effect on endothelial MMP-10 expression has not
      previously been evaluated. METHODS AND RESULTS: Thrombin induced endothelial MMP
      10 mRNA and protein levels, through a protease-activated receptor-1 (PAR-1)
      dependent mechanism, in a dose- and time-dependent manner. This effect was
      mimicked by a PAR-1 agonist peptide (TRAP-1) and antagonized by an anti-PAR-1
      blocking antibody. MMP-10 induction was dependent on extracellular regulated
      kinase1/2 (ERK1/2) and c-jun N-terminal kinase (JNK) pathways. By serial deletion
      analysis, site-directed mutagenesis and electrophoretic mobility shift assay an
      AP-1 site in the proximal region of MMP-10 promoter was found to be critical for
      thrombin-induced MMP-10 transcriptional activity. Thrombin and TRAP-1 upregulated
      MMP-10 in murine endothelial cells in culture and in vivo in mouse aorta. This
      effect of thrombin was not observed in PAR-1-deficient mice. Interestingly,
      circulating MMP-10 levels (P<0.01) were augmented in patients with endothelial
      activation associated with high (disseminated intravascular coagulation) and
      moderate (previous acute myocardial infarction) systemic thrombin generation.
      CONCLUSIONS: Thrombin induces MMP-10 through a PAR-1-dependent mechanism mediated
      by ERK1/2, JNK, and AP-1 activation. Endothelial MMP-10 upregulation could be
      regarded as a new proinflammatory effect of thrombin whose pathological
      consequences in thrombin-related disorders and plaque stability deserve further
      investigation.

PMID- 19762782
TI  - HDL3-mediated inactivation of LDL-associated phospholipid hydroperoxides is
      determined by the redox status of apolipoprotein A-I and HDL particle surface
      lipid rigidity: relevance to inflammation and atherogenesis.
AB  - OBJECTIVE: Small dense HDL3 particles of defined lipidome and proteome potently
      protect atherogenic LDL against free radical-induced oxidation; the molecular
      determinants of such antioxidative activity in these atheroprotective,
      antiinflammatory particles remain indeterminate. METHODS AND RESULTS: Formation
      of redox-active phosphatidylcholine hydroperoxides (PCOOH) and redox-inactive
      phosphatidylcholine hydroxides (PCOH) was initiated in LDL by free radical
      induced oxidation. Human HDL3 inactivated LDL-derived PCOOH (-62%, P<0.01) and
      enhanced accumulation of PCOH (2.1-fold, P<0.05); in parallel, HDL3 accumulated
      minor amounts of PCOOH. Enzyme-deficient reconstituted dense HDL potently
      inactivated PCOOH (-43%, P<0.01). HDL3-mediated reduction of PCOOH to PCOH
      occurred concomitantly with oxidation of methionine residues in HDL3
      apolipoprotein AI (apoAI). Preoxidation of methionine residues by chloramine T
      markedly attenuated PCOOH inactivation (-35%); by contrast, inhibition of HDL3
      associated enzymes was without effect. PCOOH transfer rates from oxidized LDL to
      phospholipid liposomes progressively decreased with increment in the rigidity of
      the phospholipid monolayer. CONCLUSIONS: The redox status of apoAI and surface
      lipid rigidity represent major determinants of the potent HDL3-mediated
      protection of LDL against free radical-induced oxidation. Initial transfer of
      PCOOH to HDL3 is modulated by the surface rigidity of HDL3 particles with
      subsequent reduction of PCOOH to PCOH by methionine residues of apoAI.

PMID- 19762783
TI  - Identification and functional characterization of phosphorylation sites on GTP
      cyclohydrolase I.
AB  - OBJECTIVE: The posttranslational regulation of GTP cyclohydrolase I (GCH-1), the
      rate-limiting enzyme for tetrahydrobiopterin (BH4) synthesis, remains elusive.
      Here, we identified specific phosphorylation sites on GCH-1 and characterized the
      function of these sites. METHODS AND RESULTS: Mass spectrometry studies showed
      overexpressed rat GCH-1 was phosphorylated at serine (S) 51, S167, and threonine
      (T) 231 in HEK293 cells, whereas a computational analysis of GCH-1 revealed 8
      potential phosphorylation sites (S51, S72, T85, T91, T103, S130, S167 and T231).
      GCH-1 activity and BH4 were significantly decreased in cells transfected with the
      phospho-defective mutants (S72A, T85A, T91A, T103A, or S130A) and increased in
      cells transfected with the T231A mutant. BH4 and BH2 were increased in cells
      transfected with S51E, S72E, T85E, T91E, T103D, or T130D mutants, but decreased
      in cells transfected with the T231D mutant, whereas cells transfected with the
      S167A or the S167E mutant had increased BH2. Additionally, cells transfected with
      the T231A mutant had reduced GCH-1 nuclear localization and nuclear GCH-1
      activity. CONCLUSIONS: Our data suggest GCH-1 activity is regulated either
      positively by phosphorylation S51, S72, T85, T91, T103, and S130, or negatively
      at T231. Such information might be useful in designing new therapies aiming at
      improving BH4 bioavailability.

PMID- 19762784
TI  - PCSK9 dominant negative mutant results in increased LDL catabolic rate and
      familial hypobetalipoproteinemia.
AB  - OBJECTIVE: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a central
      player in the regulation of cholesterol homeostasis, increasing the low-density
      lipoprotein (LDL) receptor degradation. Our study aimed at exploring the
      pathogenic consequences in vivo and in vitro of a PCSK9 prodomain mutation found
      in a family with hypobetalipoproteinemia (FHBL). METHODS AND RESULTS: A white 49
      year-old diabetic man had profound FBHL (LDLC: 16 mg/dL) whereas his daughter and
      sister displayed a milder phenotype (LDLC 44 mg/dL and 57 mg/dL, respectively),
      all otherwise healthy with a normal liver function. A monoallelic PCSK9 double
      mutant R104C/V114A cosegregated with FBHL, with no mutation found at other FHBL
      causing loci. A dose-effect was also found in FBHL relatives for plasma APOB and
      PCSK9 (very-low to undetectable in proband, approximately 50% decreased in sister
      and daughter) and LDL catabolic rate (256% and 88% increased in proband and
      daughter). Transient transfection in hepatocytes showed severely impaired
      processing and secretion of the double mutant which acted as a dominant negative
      over secretion of wild-type PCSK9. CONCLUSIONS: These results show that
      heterozygous PCSK9 missense mutations may associate with profound
      hypobetalipoproteinemia and constitute the first direct evidence in human that
      decrease of plasma LDLC concentrations associated to PCSK9 LOF mutations are
      attributable to an increased clearance rate of LDL.

PMID- 19762785
TI  - Acipimox, an inhibitor of lipolysis, attenuates atherogenesis in LDLR-null mice
      treated with HIV protease inhibitor ritonavir.
AB  - OBJECTIVE: The advent of HIV protease inhibitors has greatly extended the life
      span of AIDS patients. With an aging HIV(+) population, the cardiometabolic side
      effects of these drugs are becoming increasingly important clinical concerns. The
      purpose of this study was to test the hypothesis that inhibition of adipose
      lipolysis will retard atherogenic lesion development induced by the antiviral
      protease inhibitors. METHODS AND RESULTS: LDLR-null mice receiving ritonavir were
      compared with those receiving ritonavir plus lipolysis inhibitor acipimox or
      vehicle alone to determine how acipimox would affect ritonavir-induced
      atherogenesis. Intermittent high-fat high-cholesterol diet was used to facilitate
      optimal atheromatous lesion development. Drug effects were assessed as changes in
      aortic lesion score, plasma lipid and lipoprotein profile, body fat mass, and
      insulin-induced suppression of plasma fatty acid concentrations. Ritonavir
      increased aortic lesions, in association with decreased body fat mass, impaired
      antilipolysis action of insulin, and increased proatherogenic plasma
      lipoproteins. All these adverse effects were attenuated by cotreatment with
      acipimox. CONCLUSIONS: Our results provide the first direct evidence that
      supports the hypothesis that dysregulation of adipose lipolysis is an important
      contributor to the proatherogenic role of selected HIV protease inhibitors.

PMID- 19762786
TI  - Combined therapy with simvastatin and bone marrow-derived mesenchymal stem cells
      increases benefits in infarcted swine hearts.
AB  - OBJECTIVE: Widespread death of implanted cells hampers stem cell therapy for
      acute myocardial infarction (AMI). Based on the pleiotropic beneficial effects of
      statins, we examined whether simvastatin (SIMV) increased the efficacy of
      mesenchymal stem cell (MSC) transplantation after AMI. METHODS AND RESULTS:
      Chinese miniswine (n=28) were randomized to 1 of 4 groups (n=7 per group):
      control, SIMV (0.25 mg/kg x d), MSC transplantation, and SIMV+MSCs. AMI was
      created by ligating the left anterior descending coronary artery; MSCs were
      injected immediately into the cyanotic myocardium. At 6 weeks, MRI showed the
      number of dyskinetic segments and the infarct size were significantly decreased
      in the SIMV group. Cardiac function improved and the perfusion defect decreased
      significantly in the SIMV+MSC group but not in the MSC-only group (P<0.05, versus
      control group). MSC survival and differentiation were significantly better in the
      combination group than in the MSC-only group (P<0.01). Cell apoptosis decreased
      significantly in both the SIMV and the SIMV+MSC groups but not in the MSC-only
      group when compared with controls (P<0.05). Furthermore, oxidative stress and
      inflammatory response was significantly reduced in the infarcted regions in both
      the SIMV and the SIMV+MSCs groups. CONCLUSIONS: SIMV treatment improves the
      therapeutic efficacy of MSC transplantation in acutely infarcted hearts by
      promoting cell survival and cardiovascular differentiation.

PMID- 19762788
TI  - Yield and sensory properties of cheese made with milk from Holstein or
      Montbeliarde cows milked twice or once daily.
AB  - The aim of this study was to evaluate the milk properties and the yield and
      sensory properties of Cantal cheese made with milk from Holstein or Montbeliarde
      cows milked once or twice daily. Sixty-four grazing cows [32 Holstein (H) and 32
      Montbeliarde (M) cows] in the declining phase of lactation (157 d in milk) were
      allocated to 1 of 2 equivalent groups milked once daily (ODM) or twice daily
      (TDM) for 7 wk. The full-fat raw milk collected during 24 h from the 4 groups of
      cows (M-TDM, M-ODM, H-TDM, and H-ODM) was pooled and processed into Cantal cheese
      4 times during the last 4 wk of the experimental period. In all, 16 cheeses were
      made (2 milking frequencies x 2 breeds x 4 replicates) and analyzed after a
      ripening period of 15 and 28 wk. The results showed that for both breeds, the
      pooled milk content of fat, whey protein, casein, total protein, and phosphorus
      as well as rennet clotting time and curd firming time were significantly higher
      with ODM cows, whereas the casein-to-total protein ratio was lower, and lactose,
      urea, calcium, and free fatty acids contents of milk remained unchanged. The
      acidification and draining kinetics of the cheese as well as cheese yields and
      the chemical and rheological properties of the ripened cheese were not
      significantly modified by milking frequency. For both breeds, the cheeses derived
      from ODM cows had a slightly yellower coloration but the other sensory
      attributes, except for pepper odor, were not significantly affected by milking
      frequency, thereby demonstrating that ODM does not have an adverse effect on the
      sensory properties of Cantal cheese. Compared with that of Holstein cows, milk
      from Montbeliarde cows resulted in a higher cheese yield (+1.250 kg/100 kg of
      milk) and ripened cheeses with lower pH, dry matter, calcium, sodium chloride,
      and water-soluble nitrogen concentrations. These cheeses had also a less firm and
      more elastic texture, a more acidic taste, and a yogurt/whey aroma.

PMID- 19762787
TI  - Invited review: The role of contagious disease in udder health.
AB  - Contagious diseases are a threat to animal health and productivity, both
      nationally and at the farm level. This makes implementation of biosecurity
      measures to prevent their introduction and spread within countries and farms a
      necessity. Mastitis is the most common and costly contagious disease affecting
      dairy farms in the western world. The major mastitis pathogens are endemic in
      most countries, and biosecurity measures to prevent introduction and transmission
      must therefore be implemented at farm level. The 40-yr-old mastitis control plan
      remains a solid foundation to prevent the spread of contagious intramammary
      infections. Contagious diseases that do not affect the mammary gland directly may
      have an indirect effect on mastitis. This is true for list A diseases such as
      foot and mouth disease, for which biosecurity measures may need to be taken at
      national level, and for other infections with nonmastitis pathogens such as
      bovine viral diarrhea virus and Mycobacterium avium ssp. paratuberculosis.
      Maintaining a closed herd decreases the risk of introduction of pathogens that
      affect udder health directly or indirectly. If animals are purchased, their udder
      health history should be evaluated and they should be examined and tested for
      contagious diseases. Transmission of infections by and to humans and nonbovine
      animals may occur. Contact with visitors and nonbovine animals should therefore
      be minimized. Because of globalization and heightened consumer awareness, the
      importance of biosecurity now supersedes individual farms, and increased pressure
      to control transmission of contagious diseases can be expected at industry or
      government levels in western countries and elsewhere.

PMID- 19762789
TI  - An adjuvant-free mouse model to evaluate the allergenicity of milk whey protein.
AB  - Milk allergy is the most common type of food allergy in humans with the potential
      for fatality. An adjuvant-free mouse model would be highly desirable as a
      preclinical research tool to develop novel hypoallergenic or nonallergenic milk
      products. Here we describe an adjuvant-free mouse model of milk allergy that uses
      transdermal sensitization followed by oral challenge with milk protein. Groups of
      BALB/c mice were exposed to milk whey protein via a transdermal route, without
      adjuvant. Systemic IgG1 and IgE antibody responses to transdermal exposure as
      well as systemic anaphylaxis and hypothermia response to oral protein challenge
      were studied. Transdermal exposure resulted in a time- and dose-dependent
      induction of significant IgE and IgG1 antibody responses. Furthermore, oral
      challenge of sensitized mice resulted in significant clinical symptoms of
      systemic anaphylaxis within 1 h and significant hypothermia at 30 min
      postchallenge. To study the underlying mechanism, we examined allergen-driven
      spleen cell T-helper 2 cytokine (IL-4) responses. There was a robust dose- and
      time-dependent activation of memory IL-4 responses in allergic mice but not in
      healthy control mice. These data demonstrate for the first time a novel
      transdermal sensitization followed by oral challenge mouse model of milk allergy
      that does not use adjuvant. It is expected that this model may be used not only
      to study mechanisms of milk allergy, but also to evaluate novel milk products for
      allergenic potential and aid in the production of hypo- or nonallergenic milk
      products.

PMID- 19762790
TI  - Seasonal variation in the Dutch bovine raw milk composition.
AB  - In this study, we determined the detailed composition of and seasonal variation
      in Dutch dairy milk. Raw milk samples representative of the complete Dutch milk
      supply were collected weekly from February 2005 until February 2006. Large
      seasonal variation exists in the concentrations of the main components and milk
      fatty acid composition. Milk lactose concentration was rather constant throughout
      the season. Milk true protein content was somewhat more responsive to season,
      with the lowest content in June (3.21 g/100 g) and the highest content in
      December (3.38 g/100 g). Milk fat concentration increased from a minimum of 4.10
      g/100 g in June to a maximum of 4.57 g/100 g in January. The largest (up to 2
      fold) seasonal changes in the fatty acid composition were found for trans fatty
      acids, including conjugated linoleic acid. Milk protein composition was rather
      constant throughout the season. Milk unsaturation indices, which were used as an
      indication of desaturase activity, were lowest in spring and highest in autumn.
      Compared with a previous investigation of Dutch dairy milk in 1992, the fatty
      acid composition of Dutch raw milk has changed considerably, in particular with a
      higher content of saturated fatty acids in 2005 milk.

PMID- 19762791
TI  - The effect of aging on low-fat, reduced-fat, and full-fat Cheddar cheese texture.
AB  - This study investigated the effects of aging and fat content on the texture of
      Cheddar cheese, both mechanical and sensory aspects, over a 9-mo aging period.
      Cheeses of 6, 16, and 33% fat were tested at 0.5, 3, 6, and 9 mo of aging.
      Cheeses were evaluated by a trained sensory panel using an established texture
      lexicon as well as instrumental methods, which were used to probe cheese
      structure. Sensory analysis showed that low-fat cheeses were differentiated from
      full-fat cheeses by being more springy and firm and this difference widened as
      the cheeses aged. In addition, full-fat cheeses broke down more during chewing
      than the lower fat cheeses and the degree of breakdown increased with aging.
      Mechanical properties were divided by magnitude of deformation during the test
      and separated into 3 ranges: the linear viscoelastic region, the nonlinear
      region, and fracture point. These regions represent a stress/strain response from
      low to high magnitude, respectively. Strong relationships between sensory terms
      and rheological properties determined in the linear (maximum compliance) and
      nonlinear (critical stress and strain and a nonlinear shape factor) regions were
      revealed. Some correlations were seen with fracture values, but these were not as
      high as terms related to the nonlinear region of the cheeses. The correlations
      pointed to strain-weakening behavior being the critical mechanical property. This
      was associated with higher fat content cheeses breaking down more as strain
      increased up to fracture. Increased strain weakening associated with an increase
      in fat content was attributed to fat producing weak points in the protein
      network, which became initiation sites for fracture within the structure. This
      suggests that fat replacers need to serve this functional role.

PMID- 19762792
TI  - Comparison of composition, sensory, and volatile components of thirty-four
      percent whey protein and milk serum protein concentrates.
AB  - The objectives of this study were to identify and compare the composition,
      flavor, and volatile components of serum protein concentrate (SPC) and whey
      protein concentrate (WPC) containing about 34% protein made from the same milk to
      each other and to commercial 34% WPC from 6 different factories. The SPC and WPC
      were manufactured in triplicate with each pair of serum and traditional whey
      protein manufactured from the same lot of milk. At each replication, SPC and WPC
      were spray dried (SD) and freeze dried (FD) to determine the effect of the heat
      used in spray drying on sensory properties. A trained sensory panel documented
      the sensory profiles of rehydrated SD or FD powders. Volatile components were
      extracted by solid-phase microextraction (SPME) and solvent extraction followed
      by solvent-assisted flavor evaporation (SAFE) with gas chromatography-mass
      spectrometry and gas chromatography-olfactometry. Whey protein concentrates had
      higher fat content, calcium, and glycomacropeptide content than SPC. Color
      differences (Hunter L, a, b) were not evident between SPC and WPC powders, but
      when rehydrated, SPC solutions were clear, whereas WPC solutions were cloudy. No
      consistent differences were documented in sensory profiles of SD and FD SPC and
      WPC. The SD WPC had low but distinct buttery (diacetyl) and cardboard flavors,
      whereas the SD SPC did not. Sensory profiles of both rehydrated SD products were
      bland and lower in overall aroma and cardboard flavor compared with the
      commercial WPC. Twenty-nine aroma impact compounds were identified in the SPC and
      WPC. Lipid and protein oxidation products were present in both products. The SPC
      and WPC manufactured in this study had lower total volatiles and lower
      concentrations of many lipid oxidation compounds when compared with commercial
      WPC. Our results suggest that when SPC and WPC are manufactured under controlled
      conditions in a similar manner from the same milk using the same ultrafiltration
      equipment, there are few sensory differences but distinct compositional and
      physical property differences that may influence functionality. Furthermore,
      flavor (sensory and instrumental) properties of both pilot-scale manufactured
      protein powders were different from commercial powders suggesting the role of
      other influencing factors (e.g., milk supply, processing equipment, sanitation).

PMID- 19762793
TI  - Farm and factory production of goat cheese whey results in distinct chemical
      composition.
AB  - To analyze differences in fat and protein content in cheese whey (CW)
      manufactured in cheese-making factories and farms, goat CW samples were obtained
      from 60 cheese-making farms and 20 cheese factories. Gross composition of samples
      was analyzed by using an MIRIS device (MIRIS Inc., Uppsala, Sweden), whey protein
      composition was subjected to electrophoretic analysis, and fatty acid composition
      was analyzed via gas chromatography. Goat CW from farms contained higher dry
      matter content (70.6 vs. 50.8 g/L, farms vs. cheese factories, respectively) and
      a higher fat percentage (10.5 vs. 1.2% over dry matter, farms vs. cheese
      factories, respectively) than CW from cheese factories. Analysis of individual
      proteins showed that CW from farms contained higher concentrations of lactoferrin
      (0.4 vs. 0.2 mg/mL of CW, farms vs. cheese factories, respectively) and caprine
      serum albumin (0.6 vs. 0.4 mg/mL of whey, farms vs. cheese factories,
      respectively) than CW from cheese factories. No differences were observed in the
      fatty acid profile. The main fatty acids present in goat CW were C16:0, C18:1,
      C14:0, and C18:0. Thus, the origin of CW affects gross composition and the
      protein profile, but not the fatty acid profile.

PMID- 19762794
TI  - Monitoring the authenticity of low-fat yogurts by an artificial neural network.
AB  - The growing consumption of low- and reduced-fat dairy products demands routine
      control of their authenticity by health agencies. The usual analyses of fat in
      dairy products are very simple laboratory methods; however, they require
      manipulation and use of reagents of a corrosive nature, such as sulfuric acid, to
      break the chemical bounds between fat and proteins. Additionally, they generate
      chemical residues that require an appropriate destination. In this work, the use
      of an artificial neural network based on simple instrumental analyses, such as
      pH, color, and hardness (inputs) is proposed for the classification of commercial
      yogurts in the low- and reduced-fat categories (outputs). A total of 108
      strawberry-flavored yogurts (48 probiotic low-fat, 36 low-fat, and 24 full-fat
      yogurts) belonging to several commercial brands and from different batches were
      used in this research. The statistical analysis showed different features for
      each yogurt category; thus, a database was built and a neural model was trained
      with the Levenberg-Marquardt algorithm by using the neural network toolbox of the
      software MATLAB 7.0.1. Validation with unseen data pairs showed that the proposed
      model was 100% efficient. Because the instrumental analyses do not require any
      sample preparation and do not produce any chemical residues, the proposed
      procedure is a fast and interesting approach to monitoring the authenticity of
      these products.

PMID- 19762795
TI  - Nisin and lacticin 481 coproduction by Lactococcus lactis strains isolated from
      raw ewes' milk.
AB  - Bacteriocin-producing lactococci were isolated from raw ewes' milk samples
      obtained from 5 different Protected Designation of Origin Zamorano cheese
      manufacturers. Thirteen isolates with antimicrobial activity against Lactococcus
      lactis HP were selected. Eleven were identified by a PCR technique as L. lactis
      ssp. lactis and 2 were identified as L. lactis ssp. cremoris. They were grouped
      under 4 different pulsed-field gel electrophoresis patterns. The presence of
      structural genes of both nisin and lacticin 481 was detected in 10 L. lactis ssp.
      lactis isolates belonging to 2 different pulsed-field gel electrophoresis
      patterns. Coproduction of nisin and lacticin 481 was confirmed after
      semipurification by using selective indicators. The production of 2 bacteriocins
      by the same strain is an uncommon property, with relevance in food safety. Nisin
      and lacticin 481 L. lactis-producing strains might be used as adjunct cultures to
      the commercial starter in the manufacture of dairy products.

PMID- 19762796
TI  - The production of intrinsically labeled milk protein provides a functional tool
      for human nutrition research.
AB  - Oral or intravenous administration of labeled, free amino acids does not allow
      the direct assessment of protein digestion and absorption kinetics following
      dietary protein intake. Consequently, dietary protein sources with labeled amino
      acids incorporated within the protein are required. The aim of this study was to
      produce milk proteins intrinsically labeled with l-[1-(13)C]phenylalanine that
      would allow the assessment of protein digestion and absorption kinetics and the
      subsequent muscle protein synthetic response to dietary protein intake in vivo in
      humans. Two Holstein cows (body weight of 726 +/- 38 kg) were continuously
      infused with l-[1-(13)C]phenylalanine at 402 micromol/min for 44 to 48 h, during
      and after which plasma samples and milk were collected. After milk protein
      separation, casein was used in a subsequent human proof-of-principle experiment.
      Two healthy males (aged 61 +/- 1 yr; body mass index of 22.4 +/- 0.1 kg/m(2))
      ingested 35 g of casein highly enriched with [1-(13)C] phenylalanine. Plasma
      samples were collected at regular intervals, and skeletal muscle biopsies were
      collected before and 6 h after casein ingestion. In the initial experiment, a
      total of 5.83 kg of l-[1-(13)C]phenylalanine-enriched milk protein (casein
      enrichment was 29.4 molar percent excess) was collected during stable isotope
      infusion in the cows. In the proof-of-principle study, ingestion of 35 g of
      intrinsically labeled casein resulted in peak plasma l-[1-(13)C]phenylalanine
      enrichments within 90 min after protein ingestion (9.75 +/- 1.47 molar percent
      excess). Skeletal muscle protein synthesis rates calculated over the entire 6-h
      period averaged 0.058 +/- 0.012%/h. The production of intrinsically labeled milk
      protein is feasible and provides dietary protein that can be used to investigate
      protein digestion and absorption and the subsequent muscle protein synthetic
      response in vivo in humans.

PMID- 19762797
TI  - High temperature, short time pasteurization temperatures inversely affect
      bacterial numbers during refrigerated storage of pasteurized fluid milk.
AB  - The grade A Pasteurized Milk Ordinance specifies minimum processing conditions of
      72 degrees C for at least 15 s for high temperature, short time (HTST)
      pasteurized milk products. Currently, many US milk-processing plants exceed these
      minimum requirements for fluid milk products. To test the effect of
      pasteurization temperatures on bacterial numbers in HTST pasteurized milk, 2% fat
      raw milk was heated to 60 degrees C, homogenized, and treated for 25 s at 1 of 4
      different temperatures (72.9, 77.2, 79.9, or 85.2 degrees C) and then held at 6
      degrees C for 21 d. Aerobic plate counts were monitored in pasteurized milk
      samples at d 1, 7, 14, and 21 postprocessing. Bacterial numbers in milk processed
      at 72.9 degrees C were lower than in milk processed at 85.2 degrees C on each
      sampling day, indicating that HTST fluid milk-processing temperatures
      significantly affected bacterial numbers in fluid milk. To assess the microbial
      ecology of the different milk samples during refrigerated storage, a total of 490
      psychrotolerant endospore-forming bacteria were identified using DNA sequence
      based subtyping methods. Regardless of processing temperature, >85% of the
      isolates characterized at d 0, 1, and 7 postprocessing were of the genus
      Bacillus, whereas more than 92% of isolates characterized at d 14 and 21
      postprocessing were of the genus Paenibacillus, indicating that the predominant
      genera present in HTST-processed milk shifted from Bacillus spp. to Paenibacillus
      spp. during refrigerated storage. In summary, 1) HTST processing temperatures
      affected bacterial numbers in refrigerated milk, with higher bacterial numbers in
      milk processed at higher temperatures; 2) no significant association was observed
      between genus isolated and pasteurization temperature, suggesting that the genera
      were not differentially affected by the different processing temperatures; and 3)
      although typically present at low numbers in raw milk, Paenibacillus spp. are
      capable of growing to numbers that can exceed Pasteurized Milk Ordinance limits
      in pasteurized, refrigerated milk.

PMID- 19762798
TI  - Short communication: bacterial ecology of high-temperature, short-time
      pasteurized milk processed in the United States.
AB  - To determine the microbial ecology of pasteurized milk within the United States,
      2% fat pasteurized fluid milk samples were obtained from 18 dairy plants from 5
      geographical areas representing the Northeast, Southeast, South, Midwest, and
      West. Of the 589 bacterial isolates identified using DNA sequence-based subtyping
      methods, 346 belonged to genera characterized as gram-positive endospore-forming
      bacteria (i.e., Bacillus and Paenibacillus). Of the 346 gram-positive endospore
      forming bacteria isolated in the present study, 240 were classified into 45
      allelic types identical to those previously identified from samples obtained in
      New York State, indicating the widespread presence of these microbes in fluid
      milk production and processing systems in the United States. More than 84% of the
      gram-positive spore-forming isolates characterized at d 1, 7, and 10 were of the
      genus Bacillus, whereas more than 92% of isolates characterized at d 17 of shelf
      life were of the genus Paenibacillus, indicating that the predominant gram
      positive spoilage genera shifts from Bacillus spp. to Paenibacillus spp. during
      refrigerated storage.

PMID- 19762799
TI  - Short communication: effect of storage and preservation on total bacterial counts
      determined by automated flow cytometry in bulk tank goat milk.
AB  - This study was designed to evaluate the effects of different storage conditions
      on total bacterial count (TBC) determinations made in goat bulk tank milk using
      an automated flow cytometry method. The storage conditions tested were storage
      temperature (refrigeration at 4 and 10 degrees C or freezing at -20 degrees C),
      the use of a preservative (no preservative, NP; azidiol, AZ; or bronopol, BR),
      and the age of the milk samples for each analytical condition (storage times at 4
      degrees C: from 0 h to 5 d for NP; and from 0 h to 22 d for AZ and BR; storage
      times at 10 degrees C: from 24 h to 2 d for NP and from 24 h to 22 for AZ and BR;
      storage times at -20 degrees C: from 24 h to 22 d for NP, AZ, and BR).
      Significant effects on individual bacterial count (IBC) variation were shown by
      the bulk tank milk sample, preservative, storage temperature, interaction
      preservative x storage temperature, and milk age within the interaction
      preservative x storage temperature. In preserved samples, the highest IBC were
      obtained for AZ and the lowest counts were obtained in samples preserved with BR.
      Because of the variation in IBC recorded in BR-preserved samples, we recommend
      that BR should not be used for TBC determinations using the automated flow
      cytometry method. The NP samples stored at 4 and 10 degrees C showed
      significantly higher IBC at 24 h postcollection, also invalidating these
      analytical conditions for TBC analyses. The practical implications of our
      findings are that goat milk samples preserved with AZ and stored at 10 or 4
      degrees C are appropriate for TBC by the BactoScan flow cytometry method for up
      to 24 h and 11 d postcollection, respectively.

PMID- 19762801
TI  - Production response of multiparous Holstein cows treated with bovine somatotropin
      and fed diets enriched with n-3 or n-6 fatty acids.
AB  - Multiparous cows (n = 59) were blocked by expected calving date and previous milk
      yield and assigned randomly to treatments to determine the effects of bovine
      somatotropin (bST; Posilac, Monsanto Animal Agricultural Group, St. Louis, MO)
      and source of dietary fat on production responses. Diets were provided from
      calving and included whole, high-oil sunflower seeds [SS; 10% of dietary dry
      matter (DM); n-6:n-3 ratio of 4.6] as a source of linoleic acid (18:2) or a
      mixture of Alifet-High Energy and Alifet-Repro (AF; Alifet USA, Cincinnati, OH;
      3.5 and 1.5% of dietary DM, respectively; n-6/n-3 ratio of 2.6) as a source of
      protected n-3 fatty acids. Diets contained 181 versus 188 g of crude protein and
      183 versus 186 g of acid detergent fiber/kg of DM and 1.54 versus 1.66 Mcal of
      net energy for lactation at the actual DM intake for SS versus AF, respectively.
      Cows received 0 or 500 mg of bST every 10 d from 12 to 70 d in milk (DIM) and at
      14-d intervals through 280 DIM. The 2 x 2 factorial combination of diet (SS or
      AF) with or without bST administration resulted in treatments designated as SSY,
      SSN, AFY, and AFN, respectively. Data were analyzed as repeated measures using
      mixed model procedures to determine the effects of diet, bST, and their
      interactions. Yield of 3.5% fat-corrected milk was not altered by diet, but was
      increased by 4.0 +/- 1.9 kg/d from 12 to 70 DIM and by 5.1 +/- 1.2 kg/d from 12
      to 280 DIM by bST. Treatment did not affect DM intake or energy balance (EB)
      nadir. There was an interaction of bST and diet on EB because AF decreased the
      impact of bST on overall EB and allowed AFY cows to reach a positive EB earlier
      than SSY cows. Gross feed efficiency adjusted for body weight change was greater
      for bST-treated cows (1.03 vs. 1.15 +/- 0.03 kg of fat-corrected milk/Mcal of net
      energy for lactation). Circulating insulin-like growth factor-I concentrations
      were increased by bST (85 vs. 125 +/- 8 ng/mL). Body weight, body condition
      score, and backfat thickness were reduced by bST, but differences between treated
      and nontreated cows did not differ by 280 DIM. Results indicate cows responded to
      bST administration in early lactation, but the magnitude of the response was
      greater after 70 DIM. Source of dietary fat had a minimal effect on most
      production measurements, but relative to SS, AF decreased the impact of bST on
      overall EB. Results support the premise that bST administration prolongs the
      delay in postpartum tissue replenishment.

PMID- 19762800
TI  - Short communication: progression of Johne's disease curtailed by a probiotic.
AB  - The naturally occurring inflammatory bowel disease Johne's, caused by
      Mycobacterium avium ssp. paratuberculosis (MAP), has many clinical manifestations
      in common with the human inflammatory bowel disease Crohn's disease. In addition,
      both lack preventive and curative therapies. Because a high percentage of Crohn's
      patients harbor MAP, it is not surprising that MAP is at the center of
      controversy as to its contribution. Special concern is being raised as to what
      role, if any, food animals play in transmission of MAP to humans. Because
      management practices, presently considered the best way to control the spread of
      MAP, have not and most likely will not eliminate MAP from food animals, other
      preventive or curative measures are needed. The results presented herein show
      that a unique bacterium, Dietzia ssp. C79793-74, used as a probiotic, was
      therapeutic for adult paratuberculosis animals, and resulted in a cure rate of
      37.5%.

PMID- 19762802
TI  - Fatty acid composition of milk from multiparous Holstein cows treated with bovine
      somatotropin and fed n-3 fatty acids in early lactation.
AB  - Multiparous cows (n = 59) were blocked by expected calving date and previous milk
      yield and assigned randomly to treatments to determine effects of bovine
      somatotropin (bST; Posilac, Monsanto Animal Agricultural Group, St. Louis, MO)
      and source of dietary fat on milk fatty acid composition during the first 140 d
      in milk. Diets were provided from calving and included whole, high-oil sunflower
      seeds (SS; 10% of dietary dry matter; n-6/n-3 ratio of 4.6) as a source of
      linoleic acid or a mixture of Alifet-High Energy and Alifet-Repro (AF; Alifet
      USA, Cincinnati, OH; 3.5 and 1.5% of dietary dry matter, respectively; n-6/n-3
      ratio of 2.6) as a source of protected n-3 fatty acids (15.7% 18:3, 1.3% 20:5,
      and 1.3% 22:6). Treatments were derived from a 2 x 2 combination of supplemental
      fat source (SS, AF) and with 0 (SSN, AFN) or 500 (SSY, AFY) mg of bST
      administered every 10 d from 12 to 70 d in milk and at 14-d intervals thereafter.
      Milk fatty acid composition was determined in samples collected from 32 cows (8
      complete blocks) during wk 2, 8, and 20 of lactation. Data were analyzed as
      repeated measures using mixed model procedures to determine the effects of diet,
      bST, week of lactation, and their interactions. Proportions of 18:3 (4.02 vs.
      3.59 +/- 0.16%), 20:5 (0.52 vs. 0.41 +/- 0.02%), and 22:6 (0.11 vs. 0.02 +/-
      0.02%) were greater and the n-6/n-3 fatty acid ratio (7.40 vs. 8.80 +/- 0.30) was
      reduced in milk from cows fed AF compared with SS. Proportions of de novo
      synthesized fatty acids increased and preformed fatty acids decreased as
      lactation progressed, but bST administration delayed this shift in origin of milk
      fatty acids. Transfer efficiency of 18:3, 20:5, and 22:6 from AF to milk fat
      averaged 36.2, 4.9, and 5.2%, respectively. These efficiencies increased as
      lactation progressed, but were delayed by bST. Apparent mammary Delta(9)
      desaturase activity and milk conjugated linoleic acid (cis-9, trans-11 conjugated
      linoleic acid) content increased through the first 8 wk of lactation. Based on
      the product-to-substrate ratio of 14:1/14:0 fatty acids in milk, there was an
      interaction of diet and bST because bST decreased apparent Delta(9)-desaturase
      activity in SSY cows but increased it in AFY cows (0.10, 0.09, 0.08, and 0.09 +/-
      0.01 for SSN, SSY, AFN, and AFY, respectively). Feeding Alifet-Repro increased n
      3 fatty acids in milk and bST prolonged the partitioning of dietary fatty acids
      into milk fat.

PMID- 19762803
TI  - Postpartum ovarian activity in multiparous Holstein cows treated with bovine
      somatotropin and fed n-3 fatty acids in early lactation.
AB  - Multiparous cows (n = 59) were blocked by expected calving date and previous 305
      d mature-equivalent milk yield and assigned randomly to a 2 x 2 factorial design
      to determine the effects of bovine somatotropin (bST; Posilac, Monsanto Animal
      Agricultural Group, St. Louis, MO) and dietary fat on ovarian activity during the
      first 90 d in milk (DIM). Diets that included whole, high-oil sunflower seeds
      [SS; 10% of dietary dry matter; rich in linoleic acid (18:2)] or a mixture of
      Alifet-High Energy and Alifet-Repro [AF; Alifet USA, Cincinnati, OH; 3.5 and 1.5%
      of dietary dry matter, respectively; protected source of linolenic (18:3),
      eicosapentaenoic, and docosahexaenoic fatty acids] were provided from calving.
      Diets were isocaloric at equal intakes, but AF provided more net energy for
      lactation at actual intakes (1.54 vs. 1.66 Mcal/kg of dry matter). Cows received
      0 or 500 mg of bST (N, Y) every 10 d from 12 to 70 DIM and at 14-d intervals from
      70 to 280 DIM. Breeding was initiated after 90 DIM. Follicular dynamics, luteal
      growth and development (15 to 90 DIM), and plasma progesterone concentrations (1
      to 90 DIM) were evaluated (3 times per week). Days to first ovulation (33.6 +/-
      1.4) and incidence of anovulation at 45 or 70 DIM did not differ among
      treatments. Interovulatory intervals were similar among treatments (22.1 +/- 0.9
      d). Incidence of estrous cycles with 2 follicular waves was greater for SSY
      (71.0%) and AFN (80.0%) than for other groups, but more 3-wave cycles occurred
      with AFY (83.3%). Growth rate of the ovulatory follicle was greater for AF than
      SS (1.9 vs. 2.2 +/- 0.11 mm/d) and diameter of ovulatory follicles was larger for
      AFN than the other treatments (17.9 vs. 15.7 +/- 0.7 mm). Area under the
      progesterone curve was reduced for SSY (63.2, 48.1, 55.5, and 61.4 +/- 5.1
      ng.d/mL for SSN, SSY, AFN, and AFY, respectively). The number of class 1 (3 to 5
      mm) follicles was decreased and the number of class 2 (6 to 9 mm) follicles was
      increased by bST. The number of class 2 follicles was reduced by AF. Initiation
      of bST administration at 12 DIM and dietary n-3 fatty acids altered ovarian
      activity during the first 90 DIM and could benefit reproductive performance.
      Dietary n-3 fatty acids interacted with bST administration in early lactation to
      increase the incidence of estrous cycles with 3 follicular waves. Although these
      changes could benefit reproductive performance, evaluation with a larger number
      of cows is needed to determine if these alterations improve fertility.

PMID- 19762804
TI  - Hepatic gene expression in multiparous Holstein cows treated with bovine
      somatotropin and fed n-3 fatty acids in early lactation.
AB  - Multiparous cows were fed supplemental dietary fat and treated with bST to assess
      effects of n-3 fatty acid supply, bovine somatotropin (bST), and stage of
      lactation on hepatic gene expression. Cows were blocked by expected calving date
      and previous milk yield and assigned randomly to treatment. Supplemental dietary
      fat was provided from calving as either whole high-oil sunflower seeds (SS; 10%
      of dietary dry matter; n-6/n-3 ratio of 4.6) as a source of linoleic acid or a
      mixture of Alifet-High Energy and Alifet-Repro (AF; 3.5 and 1.5% of dietary dry
      matter, respectively; n-6/n-3 ratio of 2.6) as a source of protected n-3 fatty
      acids. Cows were treated with 0 (SSN, AFN) or 500 (SSY, AFY) mg of bST every 10 d
      from 12 to 70 d in milk (DIM) and at 14-d intervals thereafter. Liver biopsies
      were collected on -12, 10, 24, and 136 DIM for gene expression analysis. Growth
      hormone receptor (GHR), insulin-like growth factor-I (IGF-I), IGF-binding protein
      3 (IGFBP3), hepatic nuclear factor 4alpha (HNF4alpha), fibroblast growth factor
      21 (FGF-21), and peroxisome proliferator-activated receptor alpha (PPARalpha)
      were the target genes and hypoxanthine phosphoribosyltransferase (HPRT) was used
      as an endogenous control gene. Expression was measured by quantitative real-time
      reverse transcription-PCR analyses of 4 samples from each of 32 cows (8 complete
      blocks). Amounts of hepatic HPRT mRNA were not affected by bST or diet but were
      increased by approximately 3.8% in early lactation (3.42, 3.52, 3.54, and 3.41 x
      10(4) message copies for -12, 10, 24, and 136 DIM, respectively). This small
      change had little detectable impact on the ability of HPRT to serve as an
      internal control gene. Amounts of hepatic GHR, IGF-I, and IGFBP3 mRNA were
      reduced by 1.5 to 2-fold after calving. Expression of GHR and IGF-I increased and
      IGFBP3 tended to increase within 12 d (by 24 DIM) of bST administration. These
      effects of bST persisted through 136 DIM. Hepatic HNF4alpha mRNA was not altered
      by DIM or any of the treatments. Abundance of PPARalpha mRNA was unchanged
      through 24 DIM but increased by 136 DIM. There was a trend for an interaction of
      bST, diet, and DIM on PPARalpha mRNA abundance from 24 to 136 DIM because the
      amount of PPARalpha mRNA increased in SSN, SSY, and AFN cows but was not altered
      in AFY cows. The amount of FGF-21 mRNA increased markedly in early lactation but,
      like HNF4alpha mRNA, was not affected by bST, diet, or their interactions. These
      results indicate 1) that bST induced increases in hepatic expression of GHR, IGF
      I, and IGFBP3 when cows were in negative energy balance in early lactation, 2)
      there was no effect of reduced dietary n-6/n-3 content on hepatic gene
      expression, and 3) there was support for a potential homeorhetic role of hepatic
      FGF-21 via uncoupling the somatotropin-IGF-axis in early lactation.

PMID- 19762805
TI  - The influence of incubation on the formation of volatile bacterial metabolites in
      mastitis milk.
AB  - The possibility to detect mastitis-causing pathogens based on their volatile
      metabolites was previously studied. In that study, the mastitis samples were
      incubated overnight. To minimize the total analysis time, no incubation, or a
      short incubation, would be preferred. We therefore investigated the effect of the
      incubation time on the formation of volatile metabolites in mastitis samples. A
      selection of 6 volatile metabolites with the highest impact on the prediction
      model for identifying the mastitis-causing pathogen, was compared at different
      incubation times between 0 and 24 h. Identification of the pathogens was not
      possible without incubation. The minimum incubation time for detection of most of
      the 6 metabolites was 4 to 8 h. Although a longer incubation time increased the
      differences between pathogens, after 8 h all metabolites could be detected and
      the pathogens could be differentiated. Eight hours was therefore selected as the
      optimal incubation time. This optimal incubation time was evaluated with a set of
      25 mastitis samples, of which 88% were correctly classified after 8 h of
      incubation. The total analysis time for this method is therefore considerably
      shorter than current microbiological culturing.

PMID- 19762806
TI  - Effect of prostaglandin F2alpha on subclinical endometritis and fertility in
      dairy cows.
AB  - The objectives were to determine the effects of PGF(2alpha) treatment on the
      prevalence of subclinical endometritis (SCE) and fertility of dairy cows. A total
      of 406 Holstein cows (167 primiparous and 239 multiparous) from 5 herds were
      used. Uterine lavage for diagnosis of SCE, PGF(2alpha) treatment, evaluation of
      body condition scores (BCS), and collection of blood samples for estrous
      cyclicity determination were performed at 21, 35, and 49 d in milk (DIM).
      Polymorphonuclear cells (PMN) were quantified and thresholds for diagnosing SCE
      were selected by receiver operating characteristics analysis. Cows classified as
      having SCE at 35 DIM (>or=6.5% PMN) and 49 DIM (>or=4.0% PMN) had increased time
      to pregnancy; however, cows classified as having SCE at 21 DIM (>or=8.5% PMN) did
      not. Median days to pregnancy were delayed by 30 (151 vs. 121 d) and 40 (169 vs.
      129) d for cows classified as having SCE at 35 and 49 DIM, respectively.
      Treatment with PGF(2alpha) did not affect the prevalence of SCE either at 35
      (37.9 vs. 38.4%) or at 49 DIM (34.0 vs. 40.4%). Treatment with PGF(2alpha) did
      not affect time to first insemination (AI; median 76 DIM for cows treated with
      PGF(2alpha); 79 DIM for control. Nonetheless, PGF(2alpha) treatment increased
      pregnancy to first AI in all the cows (35.5 vs. 24.1%) and hazard ratio (HR) of
      pregnancy in cows with BCS <or=2.5 when all of the cows were evaluated (HR = 1.5;
      95% confidence interval; CI = 1.1 to 2.0) and when only cows without SCE were
      evaluated (HR = 1.8; 95% CI = 1.2 to 2.7). Treatment with PGF(2alpha) did not
      affect the hazard of pregnancy in cows with SCE at 49 DIM (HR = 0.9; 95% CI = 0.6
      to 1.3). In these farms, treatment with PGF(2alpha) did not affect SCE or time to
      first insemination, but did increase first-service pregnancy per AI and decreased
      time to pregnancy in cows with low BCS.

PMID- 19762807
TI  - Effect of the sampling device on fat and protein variation in cow milk samples
      obtained for official milk recording.
AB  - The paper was designed to assess the effect of the type of milk meter used by
      dairy farms for official milk testing to obtain individual milk samples for fat
      and protein determination. This study was performed in 2006 in Galicia, which is
      Spain's main dairy cattle region; data were collected from 2,149 Holstein cow
      farms enrolled for official milk recording. Findings indicate that the milk
      sampling system used has a substantial effect on the fat contents recorded for
      individual milk samples. Such variation could arise from poor functioning of the
      equipment, inadequate mixing of the milk portion from which the sample is
      obtained, or from the nonproportionality of the sample. Samples obtained from
      only one point in the milk line may not be representative of all the milk
      produced. The most significant differences are observed in the percentage of fat,
      whereas differences in percentage of protein are smaller. The sampling method
      used should, but does not always, provide a representative sample of the milk
      from a single milking.

PMID- 19762808
TI  - Characterization of progesterone profiles in fall-calving Norwegian Red cows.
AB  - Progesterone profiles in Norwegian Red cows were categorized, and associations
      between the occurrence of irregularities in the profiles and the commencement of
      luteal activity were investigated. The cows were managed in 3 feeding trials from
      1994 to 2001 and from 2005 to 2008 at the Norwegian University of Life Sciences.
      The cows were followed from calving, and the milk samples collected represented
      502 lactations from 302 cows. Milk samples for progesterone analysis were taken 3
      times weekly from 1994 throughout 1998 and from 2005 to 2008 and 2 times weekly
      from 1999 to 2001. Commencement of luteal activity was defined as the first day
      of 2 consecutive measurements of progesterone concentration >or=3 ng/mL not
      earlier than 10 d after calving. Delayed ovulation type I was defined as
      consistently low progesterone concentration, <3 ng/mL for >or=50 d postpartum.
      Delayed ovulation type II was defined as prolonged interluteal interval with milk
      progesterone measurements <3 ng/mL for >or=12 d between 2 luteal phases.
      Persistent corpus luteum (PCL) type I was defined as delayed luteolysis with milk
      progesterone >or=3 ng/mL for >or=19 d during the first estrous cycle postpartum.
      Persistent corpus luteum type II was defined as delayed luteolysis with milk
      progesterone >or=3 ng/mL for >or=19 d during subsequent estrous cycles before
      first artificial insemination. Delayed ovulation type I was present in 14.7%,
      delayed ovulation type II in 2.8%, PCL type I in 6.7%, and PCL type II in 3.3% of
      the profiles. Commencement of luteal activity was related to milk yield, parity,
      PCL type I, and the summated occurrence of PCL type I and II. The least squares
      means for the interval to commencement of luteal activity were 24.2 d when PCL
      type I and II were present and 29.5 d when PCL type I and II were absent. The
      likelihood of pregnancy to first service was not affected in cows with a history
      of PCL when artificial insemination was carried out at progesterone
      concentrations <3 ng/mL (i.e., during estrus); however, cows that had experienced
      PCL were more likely to be inseminated during a luteal phase. The occurrence of
      delayed ovulation and PCL in Norwegian Red cows was less than that reported in
      most other dairy populations.

PMID- 19762809
TI  - Loss of income from cows shedding Mycobacterium avium subspecies paratuberculosis
      prior to calving compared with cows not shedding the organism on two Minnesota
      dairy farms.
AB  - Quantification of the financial effect of Mycobacterium paratuberculosis
      infection on lactation performance is essential to encourage participation of
      dairy cattle producers in Johne's disease (JD) control programs. The objective of
      this study was to evaluate the differences in net income per lactation of cows
      shedding Mycobacterium paratuberculosis before calving compared with test
      negative cows. Two Minnesota dairies were enrolled in the study and fecal samples
      were collected from 1,048 cows during the close-up period. Milk production,
      clinical diseases (other than clinical JD), and reproductive performance data
      were recorded for each cow. Overall, fecal-culture-positive (FCP) cows produced
      1,355 kg less than fecal-culture-negative (FCN) cows. Fecal-culture-positive cows
      that survived their current lactation produced $276 less in milk income than cows
      that were FCN ($1,956 vs. $1,680; SD $526, $570). Fecal-culture-positive cows
      were 3.0 (95% confidence interval: 1.6-5.8) times more likely to be culled than
      FCN cows. The mean days open (number of days from calving to conception) was not
      statistically significant and the cost differences for clinical disease other
      than JD were small and neither statistically nor economically significant between
      FCP and FCN cows. Among all FCP cows, income over feed costs losses were $366 per
      cow per lactation compared with FCN cows. Among FCP nonculled cows, income over
      feed costs losses were $276 more compared with FCN cows and this difference was
      statistically significant. There was a total loss of $155 per lactation for
      nonculled FCP cows retained in the herd compared with FCN cows retained in the
      herd. Among culled cows, FCP cow losses were $50 less because of age at culling
      and $120 for reduced beef value. This totaled a loss of $441 for culled FCP cows
      compared with culled FCN cows. The losses as a result of lower lactation
      performance and early culling from the herd should alarm dairy producers and
      motivate them to implement the appropriate control measures for the disease.

PMID- 19762810
TI  - The effect of dystocia on the dry matter intake and behavior of Holstein cows.
AB  - Dairy cows that have a difficult calf delivery (dystocia) are more likely to
      develop health complications after calving, reducing productivity and welfare.
      Understanding the behavioral cues of dystocia may facilitate prompt obstetric
      assistance and reduce the long-term effect of the challenging delivery. The aim
      of this study was to describe the effects of dystocia on dairy cow behavior
      during the period around calving and to assess the use of these behaviors as
      potential indicators of dystocia. Individual dry matter intake, water intake,
      feeding and drinking time, meal size, standing time, and number of transitions
      from standing to lying positions (bouts) were recorded during the 48-h period
      before and after the time of calf delivery for 22 Holstein cows [11 cows with
      dystocia and 11 cows with unassisted delivery (eutocia)]. Cows with dystocia
      consumed 1.9 kg less during the 48 h before calving compared with cows with
      eutocia (14.3 +/- 1.0 vs. 16.2 +/- 1.0 kg, respectively), and this difference
      increased to 2.6 kg in the 24 h before calving (8.3 +/- 0.7 vs. 10.9 +/- 0.7
      kg/d). There were no differences in drinking time between the groups, but cows
      with dystocia consumed less water 24 h before calving (22.4 +/- 4.4 vs. 36.2 +/-
      4.4 kg/d, respectively) and consumed more water during the 24-h period after
      calving (56.9 +/- 3.1 vs. 48.7 +/- 3.1 kg/d) compared with cows with eutocia.
      Cows with dystocia transitioned from standing to lying positions more frequently
      than cows without dystocia beginning 24 h before calving (10.9 +/- 0.7 vs. 8.3 +/
      0.7 bouts/d). Dry matter intake and standing bouts in the 24 h before calving
      were the most accurate variables in discriminating between cows with and without
      dystocia, suggesting that cows with dystocia begin to alter their behavior
      beginning 24 h before calving.

PMID- 19762811
TI  - Efficacy of homeopathic remedies as prophylaxis of bovine endometritis.
AB  - The objective of this study was to evaluate the efficacy of 2 different
      homeopathic prophylactic strategies for the prevention of endometritis. The drugs
      used were Lachesis compositum (Lachesis), Carduus compositum (Carduus), and
      Traumeel LT (Traumeel). Each drug contained a mixed formula of homeopathic
      remedies. All 929 cows received the first treatment within 24 h postpartum. The
      second to fourth treatments were conducted at 7 to 13, 14 to 20, and 21 to 27 d
      in milk, respectively. In the first group, the 4 treatments were Traumeel,
      Lachesis, Carduus, and Carduus, respectively (n = 206). In the second group,
      Lachesis was administered 3 times, followed by 1 treatment with Carduus (n =
      198). The control group received 4 injections of saline (n = 189). In the fourth
      week after calving, the prevalence of clinical endometritis, uterine involution,
      and ovarian activity was monitored by rectal palpation and by ultrasonography. To
      assess the resumption of ovarian activity, blood samples were taken to determine
      the concentration of serum progesterone. The concentrations of beta
      hydroxybutyrate and nonesterified fatty acids in blood serum were examined to
      evaluate energy metabolism. The incidence of clinical endometritis at 21 to 27 d
      in milk did not differ between the groups (44.4, 44.8, and 36.9% in the Traumeel,
      Lachesis, Carduus, and Carduus group; the 3x Lachesis, followed by Carduus group;
      and the control group, respectively). The proportion of cows with cyclic activity
      at 21 to 27 d in milk and the proportion of cows above threshold values of
      progesterone, beta-hydroxybutyrate, and nonesterified fatty acids did not differ
      significantly between groups. When reproductive performance data were analyzed,
      no significant differences were found between groups. Hence, the treatment
      protocols tested were not effective in preventing bovine endometritis or in
      enhancing reproductive performance in this study.

PMID- 19762812
TI  - Effects of abomasal lipid infusion on liver triglyceride accumulation and adipose
      lipolysis during fatty liver induction in dairy cows.
AB  - The objective was to determine the effects of abomasal infusion of linseed oil on
      liver triglyceride (TG) accumulation and adipose tissue lipolysis during an
      experimental protocol for induction of fatty liver. Eight nonpregnant,
      nonlactating Holstein cows were randomly assigned to treatments in a replicated 4
      x 4 Latin square design. Treatments were abomasal infusion of water (W), tallow
      (T), linseed oil (LO), or half linseed oil and half tallow (LOT) at a rate of
      0.56 g/kg of body weight per day. Each experimental period consisted of a 4-d
      fast concurrent with administration of treatments into the abomasum in 6 equal
      doses per day (every 4 h). Cows were fed ad libitum for 24 d between periods of
      fasting and lipid infusion. Infusion of linseed oil (LO and LOT) increased alpha
      linolenic acid (C18:3n-3) content in serum (12.2, 10.4, 4.2, and 4.6 g/100 g of
      fatty acids for LO, LOT, T, and W, respectively), but not in the nonesterified
      fatty acid (NEFA) fraction of plasma. Treatments had no effect on plasma NEFA
      concentrations. Abomasal infusion of lipid increased in vitro stimulated
      lipolysis in subcutaneous adipose tissue, compared with W (4,294, 3,809, 4,231,
      and 3,293 nmol of glycerol released x g(-1) tissue x 2 h(-1) for LO, LOT, T, and
      W, respectively), but there was no difference between fat sources. Hepatic TG
      accumulation over 4-d fast was 2.52, 2.60, 2.64, and 2.09 +/- 0.75 microg of
      TG/microg of DNA for W, LO, LOT, and T, respectively, which did not differ.
      Abomasal infusion of LO did not reduce liver TG accumulation, plasma NEFA
      concentration, or alter in vitro adipose tissue lipolysis when compared with T.
      These results contrast with a previous study involving i.v. infusion of lipid
      emulsion derived from LO. Discrepancies might be explained by the use of
      different administration routes and a relatively modest induction of liver TG
      accumulation in the current experiment.

PMID- 19762813
TI  - Bovine subclinical mastitis caused by different types of coagulase-negative
      staphylococci.
AB  - Subclinical mastitis caused by intramammary infections (IMI) with coagulase
      negative staphylococci (CNS) is common in dairy cows and may cause herd problems.
      Control of CNS mastitis is complicated by the fact that CNS contain a large
      number of different species. The aim of the study was to investigate the
      epidemiology of different CNS species in dairy herds with problems caused by
      subclinical CNS mastitis. In 11 herds, udder quarter samples were taken twice 1
      mo apart, and CNS isolates were identified to the species level by biochemical
      methods. The ability of different CNS species to induce a persistent infection,
      and their associations with milk production, cow milk somatic cell count,
      lactation number, and month of lactation in cows with subclinical mastitis were
      studied. Persistent IMI were common in quarters infected with Staphylococcus
      chromogenes, Staphylococcus epidermidis, and Staphylococcus simulans. The results
      did not indicate differences between these CNS species in their association with
      daily milk production, cow milk somatic cell count, and month of lactation in
      cows with subclinical mastitis. In cows with subclinical mastitis, S. epidermidis
      IMI were mainly found in multiparous cows, whereas S. chromogenes IMI were mainly
      found in primiparous cows.

PMID- 19762814
TI  - Prepartum feeding behavior is an early indicator of subclinical ketosis.
AB  - Cows diagnosed with subclinical ketosis (SCK) after calving are at increased risk
      of developing other diseases and compromised reproductive performance. The
      objective of this study was to determine whether changes in feeding and social
      behaviors during the transition period were associated with SCK during the week
      after calving. Feeding behaviors of 101 Holstein dairy cows were monitored from 3
      wk before to 3 wk after calving. Ten otherwise healthy animals were identified as
      having SCK by serum beta-hydroxybutyrate levels >or=1,000 micromol/L taken during
      wk +1. These animals were matched by parity with 10 healthy animals. During the
      week before calving and the 2 wk after calving, animals with SCK had lower dry
      matter intake, had fewer visits to the feeder, and spent less time at the feeder
      than healthy animals. For every 10-min decrease in average daily time spent at
      the feeder during the week before calving, the risk of SCK increased by 1.9
      times. During the same week, a 1-kg decrease in average daily dry matter intake
      increased the risk of SCK by 2.2 times. The largest increase in risk of SCK was
      associated with a 1-kg increase in the change in average daily intake from wk -2
      to -1. During the week before calving, animals with SCK initiated fewer
      displacements at the feed bunk compared with animals that remained healthy after
      calving. The results of this study provide evidence that time spent feeding, dry
      matter intake, and social behavior play an important role in transition cow
      health. These results indicate that special consideration should be given to
      management and social factors that can negatively affect dry matter intake and
      feed bunk attendance during the transition period.

PMID- 19762815
TI  - Associations among milk quality indicators in raw bulk milk.
AB  - The objective of this study was to determine characteristics and associations
      among bulk milk quality indicators from a cohort of dairies that used modern milk
      harvest, storage, and shipment systems and participated in an intensive program
      of milk quality monitoring. Bulk milk somatic cell count (SCC), total bacteria
      count (TBC), coliform count (CC), and laboratory pasteurization count (LPC) were
      monitored between July 2006 and July 2007. Bulk milk samples were collected 3
      times daily (n = 3 farms), twice daily (n = 6 farms), once daily (n = 4 farms),
      or once every other day (n = 3 farms). Most farms (n = 11) had direct loading of
      milk into tankers on trucks, but 5 farms had stationary bulk tanks. The average
      herd size was 924 cows (range = 200 to 2,700), and daily milk produced per herd
      was 35,220 kg (range = 7,500 to 105,000 kg). Thresholds for increased bacterial
      counts were defined according to the 75th percentile and were >8,000 cfu/mL for
      TBC, >160 cfu/mL for CC, and >or=310 cfu/mL for LPC. Means values were 12,500 (n
      = 7,241 measurements), 242 (n = 7,275 measurements), and 226 cfu/mL (n = 7,220
      measurements) for TBC, CC, and LPC, respectively. Increased TBC was 6.3 times
      more likely for bulk milk loads with increased CC compared with loads containing
      fewer coliforms. Increased TBC was 1.3 times more likely for bulk milk with
      increased LPC. The odds of increased TBC increased by 2.4% for every 10,000
      cells/mL increase in SCC in the same milk load. The odds of increased CC
      increased by 4.3% for every 10,000-cells/mL increase in SCC. The odds of
      increased CC increased by 1% for every 0.1 degrees C increase in the milk
      temperature upon arrival at the dairy plant (or at pickup for farms with bulk
      tank). Laboratory pasteurization count was poorly associated with other milk
      quality indicators. Seasonal effects on bacterial counts and milk temperature
      varied substantially among farms. Results of this study can be used to aid the
      interpretation and analysis of indicators of milk quality intensively produced by
      dairy processors' laboratories.

PMID- 19762816
TI  - Short communication: methicillin-resistant Staphylococcus aureus detection in US
      bulk tank milk.
AB  - Staphylococcus aureus is a major cause of mastitis in dairy cattle. This study
      estimated the herd prevalence of methicillin-resistant Staph. aureus (MRSA) among
      US dairy herds by testing bulk tank milk (BTM) samples using genotypic and
      phenotypic methods. A nationally representative sample of 542 operations had BTM
      cultured for Staph. aureus, and 218 BTM samples were positive upon initial
      culture. After 4 wk to 4 mo of frozen storage, 87% of 218 samples (n = 190) were
      still culture positive for Staph. aureus on blood agar, but none were positive
      for MRSA on the selective indicator medium CHROMagar MRSA. A duplex PCR was used
      to detect the Staph. aureus-specific nuc gene and the methicillin resistance
      gene, mecA, in mixed staphylococcal isolates from the 190 BTM samples that were
      positive for Staph. aureus after storage. Seven samples tested positive for nuc
      and mecA, and 2 samples tested positive for mecA only. MecA-positive
      Staphylococcus spp., but not MRSA, were subsequently isolated from 5 samples,
      whereas neither mecA-positive Staphylococcus spp. nor MRSA was isolated from the
      remaining 4 samples. Presence of methicillin-resistant, coagulase-negative
      Staphylococcus spp. may complicate the detection of MRSA by means of PCR on BTM.
      Bulk tank milk in the United States is not a common source of MRSA.

PMID- 19762817
TI  - Short communication: evidence for the presence of a putative odorant-binding
      protein in bovine colostrum.
AB  - Using a combination of PAGE and mass spectrometry for protein identification, we
      obtained evidence that a putative odorant-binding protein, designated
      hypothetical protein LOC517854, occurs in bovine colostrum. This protein, termed
      as a putative bovine colostral odorant-binding protein (bcOBP), consists of 172
      AA residues, including a putative 16-AA signal peptide. The theoretical
      isoelectric point value and molecular mass of the full-length sequence of bcOBP
      were calculated to be 4.57 and 19604.18, respectively. The highest sequence
      similarity (83%) was observed with a potential pheromone transporter, Allergen
      Bos d 2. An odorant-binding protein derived from bovine nasal mucosa showed
      relatively low sequence similarity (52%) against bcOBP. Its biological function
      is unclear, but pheromone transport could be considered. This is the first report
      of a putative odorant-binding protein in bovine colostrum.

PMID- 19762818
TI  - The transfer of aflatoxin M1 in milk of ewes fed diet naturally contaminated by
      aflatoxins and effect of inclusion of dried yeast culture in the diet.
AB  - An experiment was carried out to investigate 1) the transfer of aflatoxin M1
      (AFM1) into the milk of dairy ewes fed diets naturally contaminated with
      aflatoxin B1 (AFB1); 2) the effect of the addition of dried yeast culture in the
      diet on this transfer; and 3) the alteration of enzymatic activities in the liver
      of ewes fed diets contaminated with AFB1. Twenty-four Sarda dairy ewes were
      divided in 4 groups and fed a concentrate mix containing 4 amounts of wheat meal
      naturally contaminated with aflatoxins. The diet of the control group had no
      wheat meal, whereas that of treated groups had low, medium, or high amounts of
      contaminated wheat, which corresponded to 1.13, 2.30, and 5.03 microg of AFB1/kg
      of feed, respectively. The experiment lasted 14 d. On d 8 to 14 from the
      beginning of the trial, 12 g/d of a commercial dried yeast product (DYP) of
      Kluyveromyces lactis was added to the diet of each ewe. The AFM1 concentration in
      individual milk samples and the blood serum metabolites were measured
      periodically. The presence of AFM1 was first detected in milk on d 1 of
      administration, and then its concentration increased and approached a steady
      state condition on d 3 simultaneously in all treated groups. The AFM1 in milk at
      the steady-state condition, which was linearly related to the AFB1 intake, was
      39.72, 50.38, and 79.29 ng/L in the low-aflatoxin, medium-aflatoxin, and high
      aflatoxin groups, respectively. The AFM1 concentration in milk of the high
      aflatoxin group was approximately 1.5-fold greater than the European Commission
      maximum tolerance level (50 ng/kg). The addition of DYP to the diet did not
      affect the AFM1 concentration in milk. After the withdrawal of the contaminated
      concentrate mix, the AFM1 mean concentrations decreased quickly and were no
      longer detected after 3 d in all treated groups. Daily milk yield and composition
      did not differ because of aflatoxin treatment. Blood serum parameters
      (creatinine, glutamic oxalacetic transaminase, glutamic pyruvic transaminase,
      gamma glutamyl transferase, alkaline phosphatase, lactate dehydrogenase,
      cholesterol, protein, urea, calcium, and phosphorus) were not influenced by AFB1
      intake. Therefore, the effect of DYP on certain blood parameters (gamma glutamyl
      transferase, urea, creatinine, and calcium) could not be attributed to
      amelioration of the aflatoxin-contaminated diet. In conclusion, diet
      contamination by AFB1 near the European Union tolerance level (0.005 mg/kg) in
      complete feed for dairy animals (e.g., high-aflatoxin group) can result in an
      AFM1 milk concentration higher than the European Commission maximum tolerance
      level. Transfer of aflatoxin from feed to milk was not affected by dietary
      addition of a commercial DYP.

PMID- 19762819
TI  - The development of lactic acid bacteria and Lactobacillus buchneri and their
      effects on the fermentation of alfalfa silage.
AB  - This study was conducted to document the development of populations of lactic
      acid bacteria (LAB) and Lactobacillus buchneri in alfalfa silage treated with
      various inoculants. Wilted and chopped alfalfa (45% dry matter) was treated with
      1) distilled water (untreated, U), 2) Lactobacillus buchneri 40788 (4 x 10(5)
      cfu/g; LB), or 3) L. buchneri 40788 (4 x 10(5) cfu/g) and Pediococcus pentosaceus
      (1 x 10(5) cfu/g; LBPP). Forages were packed into triplicate vacuum-sealed, nylon
      polyethylene bags per treatment, and ensiled for 2, 5, 45, 90, and 180 d. Viable
      (cfu) LAB in forage and silage were quantified by traditional plating on
      selective agar, and numbers of L. buchneri (cfu-equivalent, cfu-E) were
      quantified by real-time quantitative PCR. Fresh, untreated forage had 5.52 log
      cfu of LAB/g and 3.79 log cfu-E of L. buchneri/g. After 2 d of ensiling, numbers
      of LAB increased to >8 log cfu/g in all silages. In contrast, numbers of L.
      buchneri in U remained below 4 log cfu-E/g but reached approximately 7 log cfu
      E/g in LB and LBPP. From d 5 onward, numbers of L. buchneri in U remained below 6
      log cfu-E/g but approached 9 log cfu-E/g in LB and LBPP. The pH was lower in LBPP
      compared with U and LB after 2 and 5 d of ensiling, but pH was lower for U
      compared with LB and LBPP thereafter. Treatments LB and LBPP had more acetic acid
      than U at 45 d of ensiling, which coincided with detectable amounts of 1,2
      propanediol. Inoculation with LBPP resulted in silage with the highest
      concentration of 1,2 propanediol after 180 d of ensiling. From d 45 onward, LB
      and LBPP silages had lower concentrations of residual water-soluble carbohydrates
      but had higher concentrations of ammonia-N than U. In conclusion, epiphytic L.
      buchneri can be detected in alfalfa but this population is unable to lead the
      silage fermentation. In contrast, when L. buchneri was added to silage as an
      inoculant, the numbers of L. buchneri (cfu-E) increased markedly but did not
      dictate fermentation until 45 d of ensiling. These findings help to explain why
      the response (in increased acetic acid) from the addition of L. buchneri in
      silages is not immediate.

PMID- 19762820
TI  - Meta-analysis of milk protein yield responses to lysine and methionine
      supplementation.
AB  - Previous reports on milk protein responses to AA supplementation focused on Lys
      and Met concentrations expressed as a percentage of metabolizable protein, not
      the amounts of AA supplied. The objective of this study was to quantify the milk
      protein yield (MPY; g/d) response in studies in which Met or Lys was supplied
      either by postruminal infusion or in a rumen-protected form. A meta-analysis
      using a logistic regression model fitted using nonlinear mixed model procedures
      was performed on results from 23 published studies involving postruminal
      supplementation of Lys (18 experiments) and Met (35 experiments) in lactating
      dairy cows. Variance caused by study effect was removed by designation of
      individual study as subject within the random component within the nonlinear
      model. Milk protein responses to supplemental Met decreased from 16 to 4 g of
      milk protein per gram of metabolizable Met intake as Met intake varied from 25 to
      70 g per cow per day. Similarly, milk protein responses to supplemental Lys
      decreased from 5.0 to 3.2 g of milk protein per gram of metabolizable Lys intake
      as Lys intake varied from 80 to 203 g per cow per day. Assuming Met and Lys
      concentrations of 2.76 and 7.63 g/100 g of milk protein, respectively, the
      implied marginal efficiencies of metabolizable AA use for MPY decreased from 44
      to 12% for Met and from 39 to 25% for Lys over the range of metabolizable AA
      intakes. Although the estimated efficiencies were low compared with previous
      estimates, a low marginal efficiency of amino acid utilization would be expected
      when amino acid supply is at or near to the animal's requirement, as was the case
      in these experiments. This suggests that current models that assume both a
      constant MPY response and constant AA utilization efficiency are inadequate.
      Models that assume a constant efficiency of AA use will overestimate production
      responses to individual AA supply, especially when high amounts of metabolizable
      AA are fed.

PMID- 19762821
TI  - A meta-analysis of feed digestion in dairy cows. 1. The effects of forage and
      concentrate factors on total diet digestibility.
AB  - A meta-analysis based on published experiments with lactating dairy cows was
      conducted to study the effects of dietary forage and concentrate factors on
      apparent total diet digestibility. A data set was collected that included a total
      of 497 dietary treatment means from 92 studies. The diets were based on grass
      silage or on legume or whole-crop cereal silages partly or completely substituted
      for grass silage. The silages were supplemented with concentrates given at a flat
      rate within a dietary comparison. For the statistical evaluation, the data were
      divided into 5 subsets to quantify silage (digestibility, 42 diets in 17 studies;
      fermentation characteristics, 108 diets in 39 studies) and concentrate (amount of
      supplementation, 142 diets in 59 studies; concentration of crude protein, 215
      diets in 82 studies; carbohydrate composition, 66 diets in 23 studies) factors on
      total diet digestibility. The diet digestibility of dairy cows was determined by
      total fecal collection or by using acid-insoluble ash as an internal marker. Diet
      organic matter digestibility (OMD) at a maintenance level of feeding (OMD(m)) was
      estimated using sheep in vivo or corresponding in vitro digestibility values for
      the forage and reported ingredient and chemical composition values, with
      tabulated digestibility coefficients for the concentrate components of the diet.
      A mixed model regression analysis was used to detect the responses of different
      dietary factors on apparent total diet digestibility. Improved silage OMD(m)
      resulting from earlier harvest was translated into improved production-level OMD
      in cows (OMD(p)). The effects of silage fermentation characteristics on OMD(p)
      were quantitatively small, although sometimes significant. Concentrate
      supplementation improved total diet OMD(m), but this was not realized in
      lactating dairy cows because of linearly decreased neutral detergent fiber (NDF)
      digestibility as concentrate intake increased. Increasing the concentrate crude
      protein amount quadratically improved OMD(p) in cows, with the response being
      mostly due to improved NDF digestibility. Replacement of starchy concentrates
      with fibrous by-products slightly decreased OMD(p) but tended to improve NDF
      digestibility. The true digestibility of cell solubles (OM - NDF) estimated by
      the Lucas test both from all data and from the data subsets was not significantly
      different from 1.00, suggesting that responses in OMD(p) of dairy cows are
      mediated through changes in the concentration and digestibility of NDF.

PMID- 19762822
TI  - A meta-analysis of feed digestion in dairy cows. 2. The effects of feeding level
      and diet composition on digestibility.
AB  - A meta-analysis based on published experiments with lactating dairy cows fed
      mainly grass silage-based diets was conducted to study the effects of intake,
      diet composition, and digestibility at a maintenance level of feeding on the
      apparent total diet digestibility. A data set that included a total of 497
      dietary treatment means from 92 studies was collected and analyzed using mixed
      model regression analysis with a random study effect. Diet organic matter
      digestibility (OMD) in dairy cows at a production level (OMD(p)) was positively
      associated with OMD at maintenance (OMD(m)), but the slope was less than 1
      (0.69). Diet OMD(p) decreased as feed intake increased, and diets with high
      OMD(m) exhibited greater depressions in digestibility with increased intake than
      did diets with low OMD(m). Digestibility of organic matter and neutral detergent
      fiber (NDF) increased as dietary crude protein concentration increased, whereas
      increased concentrate fat decreased digestibility. Replacement of grass silage
      with whole-crop cereal silage was associated with a quadratic decrease in diet
      digestibility. Metabolic fecal output, defined as fecal organic matter minus NDF,
      averaged 95.8 (SE = 0.65) g/kg of dry matter intake, and it was not influenced by
      intake or diet composition. Variation in OMD(p) in cows fed grass silage-based
      diets was therefore attributable to variation in dietary NDF concentration and
      NDF digestibility. Depression in digestibility of organic matter with increased
      intake was less than predicted by the National Research Council and Cornell Net
      Carbohydrate and Protein systems. The following 2-parameter model indicates that
      the difference between OMD estimated in sheep fed at maintenance compared with
      dairy cows at production level is related both to dry matter intake and
      digestibility at maintenance level: OMD(p) = 257 (+/-43) + 0.685 (+/-0.054) x
      OMD(m) (g/kg of dry matter) - 2.6 (+/-0.44) x dry matter intake (kg/d); adjusted
      residual mean square error = 8.4 g/kg. It was concluded that diet digestibility
      in dairy cows can be predicted accurately and precisely from digestibility
      estimated at maintenance intake in sheep by using regression models including
      animal and dietary factors.

PMID- 19762823
TI  - Altering the representation of hormones and adding consideration of gestational
      metabolism in a metabolic cow model reduced prediction errors.
AB  - The model of R. L. Baldwin predicts various aspects of digestion and metabolism
      in the cow including nutrient partitioning between milk and body stores. However,
      prediction bias has been observed for body weight (BW) and body condition score
      (BCS) when diets of differing energy density are simulated over long periods.
      Originally, the model overpredicted BW loss in early lactation and gain in late
      lactation. This bias was reversed and limited to early lactation when a better
      representation of milk synthesis capacity was introduced into the model. It was
      hypothesized that a better representation of the effects of energy status on
      anabolic and catabolic hormones and a more complete representation of metabolic
      demands and growth associated with pregnancy would help in improving predictions
      of body tissue mobilization in early lactation. Providing independent glucose
      reference points and independent sensitivity scalars for the 3 hormones driven by
      glucose concentrations improved overall model precision. These improvements were
      primarily realized through reductions in prediction errors for blood glucose
      concentrations and BCS. In both cases, slope bias associated with the predictions
      was reduced, indicating that the changes in representation were beneficial
      although BCS bias was not completely removed. Milk component yields were
      predicted with slightly greater mean and slope bias. The addition of enhanced
      pregnancy calculations did not provide apparent additional benefit relative to
      model prediction errors. However, the data used for the assessments did not
      include observations from the last 60 d of gestation, where BW gain and metabolic
      demand associated with pregnancy would be expected to be greater. Improvements in
      BCS were not observed when the revised model was tested using an independent data
      set. Predictions of blood fatty acids, the rate of BCS and BW loss, and milk fat
      yields in early lactation were still inappropriate and require further work. The
      results could be caused by inaccurate early lactation intakes, the aggregated
      representation of blood fatty acids, or an inadequate representation of
      peripheral insulin resistance during early lactation.

PMID- 19762824
TI  - Enteropathogens and risk factors for diarrhea in Norwegian dairy calves.
AB  - The aims of the current study were to estimate the prevalence of enteropathogens
      in calves in Norwegian dairy herds, evaluate the clinical consequences of
      protozoal infections, and identify risk factors for diarrhea. The 135
      participating herds were randomly selected from those in The Norwegian Dairy Herd
      Recording System that had at least 15 cow-years. Each herd was followed for 1 yr.
      Fecal samples from calves with (n = 68) or without (n = 691) diarrhea were
      analyzed for the presence of Cryptosporidium, Giardia, and Eimeria species.
      Diarrheic samples (n = 191) were assayed for rotavirus group A, bovine
      coronavirus (BCoV), Cryptosporidium, and Escherichia coli F5 by antigen ELISA.
      Blood samples (n = 1,348) were analyzed for antibodies against BCoV and
      rotavirus. Potential risk factors for diarrhea were analyzed by using Cox
      regression analysis adjusted for herd frailty effect. Rotavirus and
      Cryptosporidium were the most commonly detected enteropathogens in diarrheic
      samples. A high level of Cryptosporidium shedding or BCoV seropositive calves in
      a herd was associated with an increased risk of diarrhea. Other factors found to
      increase the risk of diarrhea were use of slatted concrete floor in group pens
      versus other floor types [hazard ratio (HR) = 8.9], housing of calves in free
      stalls compared with tie-stalls (HR = 3.7), purchasing of calves into the herd
      versus not purchasing calves (HR = 4.1), and calves being born during winter
      compared with other seasons of the year (HR = 1.5).

PMID- 19762825
TI  - Repeated ruminal acidosis challenges in lactating dairy cows at high and low risk
      for developing acidosis: feeding, ruminating, and lying behavior.
AB  - An experiment was conducted to determine whether the susceptibility to ruminal
      acidosis, as defined through differences in days in milk (DIM), milk production
      level, and ration composition, influences cow feeding, ruminating, and lying
      behavior and whether these behaviors change during an acute bout of ruminal
      acidosis. Eight ruminally cannulated cows were assigned to 1 of 2 acidosis risk
      levels: low risk (LR, mid-lactation cows fed a 60:40 forage:concentrate ratio
      diet) or high risk (HR, early lactation cows fed a 45:55 forage:concentrate
      diet). As a result, diets were intentionally confounded with DIM and milk
      production to represent 2 different acidosis risk scenarios. Cows were exposed to
      an acidosis challenge in each of three 14-d periods. Each period consisted of 3
      baseline days, a feed restriction day (restricting total mixed ration to 50% of
      ad libitum intake), an acidosis challenge day (1 h meal of 4 kg of ground
      barley/wheat before allocating the total mixed ration), and a recovery phase.
      Feeding, rumination, and standing/lying behavior were recorded for 2 baseline
      days, on the challenge day, and 1 and 4 d after the challenge day for each cow.
      Across the study, there were no differences in measures of standing, lying, or
      feeding behavior between the 2 groups of cows. The HR cows did, on average, spend
      less time ruminating (491 vs. 555 min/d) than the LR cows, resulting in a lesser
      percentage of observed cows ruminating across the day (44.6 vs. 48.1%). The
      acidosis challenge resulted in changes in behavior in all cows. Compared with the
      baseline, feeding time increased on the first day after the challenge (395 vs.
      310 min/d), whereas lying time decreased (565 vs. 634 min/d). Rumination time
      decreased the first day following the challenge (436 min/d) relative to the
      baseline (533 min/d), but increased the following day (572 min/d). Fewer cows
      were observed to be ruminating at a given time on the first day following the
      challenge as compared with the baseline period. Despite this, on a herd level,
      numerous observations of the proportion of cows ruminating at any one time would
      need to be taken to accurately detect an acute bout of acidosis using changes in
      rumination behavior. Overall, these results suggest that risk of acidosis may
      have little overall effect on general behavior, with the exception of rumination.
      Furthermore, an acute bout of acidosis alters behavioral patterns of lactating
      dairy cows, particularly rumination behavior, and identification of these changes
      in behavior through repeated measurements may assist in the detection of an
      acidosis event within a herd.

PMID- 19762826
TI  - Ionized calcium requirement of rumen cellulolytic bacteria.
AB  - Ionized calcium (Ca(+2)) appears to be required by the 3 predominant species of
      rumen cellulolytic bacteria, Fibrobacter succinogenes, Ruminococcus flavefaciens,
      and Ruminococcus albus. The present study evaluated the role of ionized calcium
      in growth and cellulose digestion. Maximum growth or rate and extent of digestion
      and lag time were the criteria used to evaluate Ca(+2) requirements. All cultures
      except F. succinogenes A3c grew when repeatedly transferred in a medium without
      added Ca(+2). As Ca(+2) concentration increased in cellobiose medium, the rate of
      growth increased and lag time decreased for F. succinogenes A3c, whereas F.
      succinogenes S85 exhibited increases in both maximum growth and rate of growth.
      No responses in any of the criteria were observed for the ruminococci in
      cellobiose medium. Both strains of F. succinogenes had an absolute requirement
      for Ca(+2) with cellulose as the only substrate. For strain A3c the requirement
      was 0.36 to 0.42 mM and for S85, >0.64 mM. Increases in extent of cellulose
      degradation occurred with all strains of ruminococci as Ca(+2) concentration
      increased; however, degradation in Ca(+2)-free medium was similar to that of F.
      succinogenes with Ca(+2). Although the ruminococci presumably have cellulosomes
      that require Ca(+2) in their structure, such was not evident in our studies. The
      function of Ca(+2) in cellulose degradation by F. succinogenes is unknown, but
      may be related to the secretion or activation of their cellulolytic enzymes.
      Based on reported concentrations of Ca(+2) in the rumen, it seems unlikely that
      an in vivo deficiency would occur for these bacteria.

PMID- 19762827
TI  - Glucagon increases hepatic mRNA concentrations of ureagenic and gluconeogenic
      enzymes in early-lactation dairy cows.
AB  - Exogenous glucagon increases hepatic glucose synthesis in part by increasing
      hepatic extraction of amino acids from blood for conversion to glucose. To
      examine the role of glucagon in orchestrating gene expression of gluconeogenic
      and ureagenic enzymes, we determined the mRNA concentrations of key hepatic
      ureagenic and gluconeogenic enzymes at d 11, 15, and 22 postpartum in multiparous
      Holstein cows that received 0 or 5 mg of glucagon in 60 mL of saline by
      subcutaneous injection every 8 h for 14 d starting on d 8 postpartum. On d 11
      postpartum, glucagon increased the hepatic mRNA concentrations for all measured
      ureagenic enzymes (carbamoylphosphate synthetase I, ornithine transcarbamylase,
      and argininosuccinate synthetase) and gluconeogenic enzymes (pyruvate carboxylase
      and cytosolic and mitochondrial forms of phosphoenolpyruvate carboxykinase) and
      increased or tended to increase mRNA concentrations of gluconeogenic enzymes on d
      15 postpartum but not on d 22. The effect of glucagon to increase mRNA
      concentrations of ureagenic and gluconeogenic enzymes was limited to times when
      concentrations of plasma insulin were not increased. Our results suggest that
      hepatic gene expression of key ureagenic and gluconeogenic enzymes in early
      lactation dairy cows is responsive to hormonal regulation by glucagon.

PMID- 19762828
TI  - Effect of limit feeding high- and low-concentrate diets with Saccharomyces
      cerevisiae on digestibility and on dairy heifer growth and first-lactation
      performance.
AB  - Growth and digestibility were examined for heifers limit fed high- (HC; 60%) and
      low-concentrate (LC; 20%) diets with or without yeast culture (YC) addition in 2
      experiments. A third experiment was undertaken to monitor first-lactation
      production of heifers limit fed HC or LC diets. In experiment 1, 32 Holstein
      heifers were individually fed at controlled intakes for 133 d to maintain a
      targeted average daily gain of 0.80 kg/d for all 4 treatments [HC; LC with and
      without Saccharomyces cerevisiae; Yea-Sacc(1026) (Alltech Inc., Nicholasville,
      KY), 1 g/kg as fed]. Targeted average daily gain was achieved for all treatments
      during the individual feeding period (0.80 +/- 0.01 kg/d). Average dry matter
      intake needed to maintain constant gain was slightly reduced for HC and YC
      treatments. Reduced dry matter intake and similar targeted average daily gain
      resulted in a tendency for improved feed efficiency of HC-fed heifers. Skeletal
      measurements and targeted average daily gain were not affected by concentrate
      level or YC. The objective of experiment 2 was to elucidate effects of
      concentrate level and YC on nutrient digestibility. Four young (284.35 +/- 4.51
      d) and 4 older (410.28 +/- 2.14 d) heifers were allocated to the 4 treatments
      used in experiment 1. Heifers fed the HC diet had increased dry matter
      digestibility (75.67 vs.72.96 +/- 0.72%), and YC addition increased dry matter
      digestibility (74.97 vs. 73.65 +/- 0.71%). Intake of N and apparent N
      digestibility were similar for all treatments. High-concentrate diets and YC
      addition decreased wet and dry matter output of feces. Urine excretion was not
      different; therefore, total manure output was lower for HC-fed heifers as
      compared with LC-fed heifers. Results suggest that HC diets can improve feed
      efficiency without affecting growth when limit fed to dairy heifers. Yeast
      culture increased dry matter digestibility in HC- and LC-fed heifers; HC diets
      were more digestible and reduced fecal output, with YC enhancing this effect. In
      experiment 3, heifers from experiment 1 were group fed the same diets (HC or LC)
      without YC until parturition, and milk production was measured through 154 d of
      lactation. Group-fed average daily gain was not different between treatments (HC
      = 1.11 vs. LC = 1.04 kg/d, SE = +/-0.06 kg/d). Heifers fed the HC and LC diets
      calved at 23.50 and 23.79 +/- 0.50 mo, respectively. Peak milk was lower and
      there was a tendency for reduced daily milk and protein yield for primiparous
      cows fed HC diets from 8 mo of age to the dry/prefresh period (long term), but
      predicted yields of milk and components were similar in the first 154 d of
      lactation.

PMID- 19762829
TI  - Feeding value of glycerol as a replacement for corn grain in rations fed to
      lactating dairy cows.
AB  - Growth of the corn ethanol industry has created a need for alternatives to corn
      for lactating dairy cows. Concurrent expansion in soydiesel production is
      expected to increase availability and promote favorable pricing for glycerol, a
      primary co-product material. The objective of this study was to determine the
      feeding value of glycerol as a replacement for corn in diets fed to lactating
      dairy cattle. Sixty lactating Holstein cows housed in individual tie stalls were
      fed a base diet consisting of corn silage, legume forages, corn grain, soyhulls,
      roasted soybeans, and protein supplements. After a 2-wk acclimation period, cows
      were fed diets containing 0, 5, 10, or 15% refined glycerol for 56 d. Cows were
      milked twice daily and weekly milk samples were collected. Milk production was
      36.3, 37.2, 37.9, and 36.2 +/- 1.6 kg/d and feed intake was 23.8, 24.6, 24.8, and
      24.0 +/- 0.7 kg/d for 0, 5, 10, and 15% glycerol treatments, respectively, and
      did not differ except for a modest reduction in feed intake during the first 7 d
      of the trial for 15% glycerol (treatment x time effect). Milk composition was not
      altered by glycerol feeding except that milk urea nitrogen was decreased from
      12.5 +/- 0.4 to 10.2 +/- 0.4 mg/dL with glycerol addition. Cows fed diets
      containing 10 and 15% glycerol gained more weight than those fed rations
      containing 0 or 5% glycerol but body condition scores did not differ with
      glycerol feeding. The data indicate that glycerol is a suitable replacement for
      corn grain in diets for lactating dairy cattle and that it may be included in
      rations to a level of at least 15% of dry matter without adverse effects on milk
      production or milk composition.

PMID- 19762830
TI  - Effects of feeding three types of corn-milling coproducts on milk production and
      ruminal fermentation of lactating Holstein cattle.
AB  - Two experiments were conducted to determine the effects of feeding 3 corn-milling
      coproducts on intake, milk production, ruminal fermentation, and digestibility of
      lactating Holstein cows. In experiment 1, three corn-milling coproducts were fed
      at 15% of the diet dry matter (DM) to 28 Holstein cows averaging (+/-SD) 625 +/-
      81 kg of body weight and 116 +/- 33 d in milk to determine effects on DM intake
      and milk production. In experiment 2, the same rations were fed to 4 ruminally
      fistulated, multiparous Holstein cows averaging 677 +/- 41 kg of body weight and
      144 +/- 5 d in milk to determine the effects on ruminal fermentation and
      digestibility. In both experiments, cows and treatments were assigned randomly in
      4 x 4 Latin squares over four 21-d periods. Treatments were formulated by
      replacing portions of forage and concentrate feeds with 15% coproduct and
      included 1) 0% coproduct (control), 2) dried distillers grains plus solubles
      (DDGS), 3) dehydrated corn germ meal (germ), and 4) high-protein dried distillers
      grains (HPDDG). Feed intake was recorded daily, and milk samples were collected
      on d 19 to 21 of each period for analysis of major components. Rumen fluid was
      collected at 10 time points over 24 h post feeding on d 21 of experiment 2. In
      experiment 1, DM intake was greater for the germ (24.3 kg/d) and DDGS treatments
      (23.8 kg/d), but DDGS was not different from the control (22.9 kg/d) and HPDDG
      treatments (22.4 kg/d). Milk production paralleled DM intake and tended to be
      greater for the germ (32.1 kg/d) and DDGS treatments (30.9 kg/d), but the DDGS
      treatment was not different from the control (30.6 kg/d) and HPDDG treatments
      (30.3 kg/d). However, yields of milk fat, milk protein, and 3.5% FCM were similar
      and averaged (+/-SEM) 1.1 +/- 0.1, 0.9 +/- 0.03, and 31.7 +/- 1.3 kg/d. Milk urea
      nitrogen was greater for the HPDDG (15.9 mg/dL) and germ treatments (15.5 mg/dL)
      than for the control (15.0 mg/dL) and DDGS treatments (14.9 mg/dL). In experiment
      2, DM intake and milk production were not different across treatments and
      averaged 26.1 +/- 2.3 and 28.3 +/- 3.9 kg/d. Ruminal pH (6.26 +/- 0.08) and total
      concentration of volatile fatty acids (125.3 +/- 4.2 mM) were similar. Acetate
      concentration was higher for the control treatment than the DDGS, germ, and HPDDG
      treatments (81.7 vs. 75.8, 75.0, and 78.4 mM). Concentrations of propionate and
      butyrate were not different and averaged 27.8 +/- 1.2 and 14.3 +/- 0.9 mM across
      treatments. The acetate:propionate ratios for the control, germ, and HPDDG
      treatments were greater than for the DDGS treatment (3.02, 2.88, and 2.91 vs.
      2.62). Dry matter, organic matter, and neutral detergent fiber digestibilities
      were similar across treatments and averaged 63.5 +/- 2.7, 67.3 +/- 2.2, and 43.5
      +/- 4.2%. Milk production followed DM intake in experiment 1, and yield of major
      milk components was not affected. Results of these experiments indicate that
      dairy rations can be successfully formulated to include 15% of diet DM as corn
      milling coproducts while maintaining or increasing DM intakes and yields of milk
      and milk components.

PMID- 19762831
TI  - The effect of dietary iodine supplementation in dairy goats on milk production
      traits and milk iodine content.
AB  - Dairy products offer an important source of iodine for humans, particularly
      infants and children. An adequate iodine content in the diet of lactating animals
      must guarantee a suitable milk iodine concentration. In this experiment, the
      effects of iodine supplementation of dairy goat diets on the iodine
      concentration, milk yield, and milk composition of goat milk were studied. Thirty
      crossbred dairy goats of the Sarda population were divided into 3 groups
      supplemented with 0 (control group), 0.45 (group 1), or 0.90 (group 2) mg of KI/d
      per goat. The dose of KI (76.5% of iodine) was dissolved in water and orally
      administered with a syringe every day for 10 wk. Mean milk iodine concentrations
      were 60.1 +/- 50.5, 78.8 +/- 55.4, and 130.2 +/- 62.0 microg/L (mean +/- SD) in
      the control group, group 1, and group 2, respectively. The extent of iodine
      enrichment in milk was approximately 31% in group 1 and 117% in group 2 compared
      with the control group. Milk yield was not influenced by KI supplementation and
      averaged 1,229, 1,227, and 1,179 g/d in groups 0, 1, and 2, respectively. Milk
      urea nitrogen concentration was significantly lower in the KI-supplemented groups
      (32 and 33 mg/dL in groups 1 and 2, respectively) than in the control group (37
      mg/dL). Iodine supplementation of dairy goat diets can increase milk iodine
      content without adverse effects on milk production traits.

PMID- 19762832
TI  - Respiratory infections in Norwegian dairy calves.
AB  - The aims of this study were to estimate the seroprevalence of respiratory agents
      in Norwegian dairy calves and to identify risk factors for respiratory disease.
      The participating 135 herds were randomly selected from those in The Norwegian
      Dairy Herd Recording System with at least 15 cow years. Each herd was followed
      for 1 yr. Blood samples from calves of >150 d of age (n = 1,348) were analyzed
      for antibodies against parainfluenza virus 3, bovine coronavirus (BCoV), bovine
      respiratory syncytial virus (BRSV), and Mycoplasma bovis. Calves reported to have
      been on pasture (n = 139) were tested for antibodies against Dictyocaulus
      viviparus. Seroprevalences for parainfluenza virus 3, BCoV, BRSV, and D.
      viviparus at the calf level were 50.2, 39.3, 31.2, and 4.3%, respectively. No
      calves were antibody positive for M. bovis. Calves in herds with BCoV
      seropositive calves had an increased risk of respiratory disease compared with
      herds in which BCoV antibodies were not detected [hazard ratio (HR) = 3.9], as
      had calves in herds in which the majority (>54%) of the sampled calves were
      seropositive for BRSV (HR = 2.7). Other factors found to increase the risk of
      respiratory disease in calves were shared housing with cows during the first week
      of life compared with separate housing (HR = 16.7), a larger herd size (>50 cow
      years) compared with smaller herds (HR = 8.2), more than an 8-wk age difference
      between calves housed together in the same group pen compared with having pen
      mates of a more similar age (HR = 3.9), previous recordings of diarrhea compared
      with no recorded diarrhea (HR = 3.9), and leaving calves with dams for >24 h
      after birth compared with earlier separation (HR = 3.5).

PMID- 19762833
TI  - Effects of fat concentration of a high-protein milk replacer on calf performance.
AB  - The hypothesis was that calves fed high-fat milk replacers (MR) would have
      reduced starter intake, digestibility, and average daily gain (ADG). Forty-eight
      Holstein calves (initially 42.4 +/- 1.5 kg of body weight, 2 to 3 d of age; 12
      calves/treatment) were fed 0.66 kg dry matter (DM) of MR per calf daily that
      contained 14, 17, 20, or 23% fat. This MR had crude protein (CP) to metabolizable
      energy (ME) ratios ranging from 51.6 to 56.7 g of CP/Mcal of ME, which were above
      and below a previously determined optimum. Calves were weaned at 28 d;
      postweaning measurements were continued to d 56. A 20% CP starter and water were
      fed ad libitum all 56 d of the trial. Measurements of digestion were made using
      chromic oxide as a marker in the MR and starter from fecal samples collected on d
      19 to 23 from 4 calves/treatment. Selected serum constituents were measured on d
      21. Calves were housed individually in pens bedded with straw within a naturally
      ventilated barn with no added heat. The average barn temperature was 2 degrees C.
      Data were analyzed as a completely randomized design using polynomial contrasts
      to separate differences in the means. Preweaning apparent digestibility of DM,
      organic matter, fat, nonfiber carbohydrates, Ca, and P and serum amylase
      concentration were linearly reduced as fat increased from 14 to 23%. Preweaning
      starter intake responded quadratically to fat, being lowest at 14 and 23% fat. A
      reduction in digestibility and starter intake contributed to less ADG at the
      higher fat concentrations in the MR. A 27% CP, 17% fat MR with 55 g of CP/Mcal of
      ME maximized preweaning ADG when fat concentration was varied to obtain various
      CP to ME ratios in the MR. Additionally, a 27% CP, 20% fat MR with 53 g of
      CP/Mcal of ME supported overall ADG similar to calves fed the 17% fat MR but
      preweaning digestion measurements and serum amylase concentrations were less than
      in calves fed the 17% fat MR.

PMID- 19762834
TI  - Effects of providing two forms of supplemental methionine to periparturient
      Holstein dairy cows on feed intake and lactational performance.
AB  - Eighteen primiparous and 42 multiparous Holstein cows were blocked according to
      parity and expected calving date and assigned randomly to 1 of 3 dietary
      treatments: 1) a basal diet (negative control), 2) the basal diet plus 2-hydroxy
      4-methylthio butanoic acid isopropyl ester (MetaSmart, Adisseo Inc., Antony,
      France), or 3) the basal diet plus rumen-protected Met (Smartamine M, Adisseo
      Inc., Alpharetta, GA). Treatments were initiated 21 d before expected calving and
      continued through 140 d postpartum. Diets were similar in ingredient and chemical
      composition, except for the content of Met in metabolizable protein. MetaSmart
      [0.35% prepartum and 0.54% postpartum in diet dry matter (DM)] and Smartamine M
      (0.06% prepartum and 0.10% postpartum in diet DM) were added to the basal diet in
      amounts needed to achieve a 3.0:1 ratio of Lys to Met in metabolizable protein.
      Prepartum DM intake (DMI; 13.5 kg/d), body weight (687 kg), body condition score
      (3.81), postpartum milk yield (42.0 kg/d), milk fat yield (1,549 g/d), milk fat
      content (3.66%), milk true protein yield (1,192 g/d), and milk urea N content
      (12.9 mg/dL) were not different among treatments. Postpartum DMI and body
      condition score were greater and the ratios of milk:DMI and milk N:feed N were
      less for cows fed the MetaSmart diet than for cows fed the control and Smartamine
      M diets. Milk protein content was greater for the Smartamine M (2.87%) and
      MetaSmart (2.81%) treatments than for the control treatment (2.72%).
      Concentrations of Met and Met + Cys in total plasma AA were different among
      treatments, with values for the Smartamine M treatment being the highest,
      followed by the MetaSmart and control treatments. The results indicated that both
      MetaSmart and Smartamine M are effective in providing metabolizable Met, but
      clarification of their relative contributions to metabolizable Met is still
      needed.

PMID- 19762835
TI  - Effects of intravenous infusion of trans-10, cis-12 18:2 on mammary lipid
      metabolism in lactating dairy cows.
AB  - It has previously been established that supplementation of trans-10, cis-12 18:2
      reduces milk fat content and fat deposition in several species. The objectives of
      the study were 1) to examine whether potential mechanisms by which trans-10, cis
      12 18:2 is reported to affect lipid metabolism in adipose tissue of different
      species could be partly responsible for the inhibition in milk fat synthesis in
      lactating dairy cows; and 2) to investigate the effects of trans-10, cis-12 18:2
      on the expression of a newly identified isoform of stearoyl-coenzyme A desaturase
      (SCD) in bovine mammary tissue. Four primiparous Holstein cows in established
      lactation, fitted with indwelling jugular catheters, were used in a balanced 2 x
      2 crossover design. For the first 5 d of each period, cows were infused
      intravenously with a 15% lipid emulsion providing 10 g/d of either cis-9, cis-12
      18:2 (control) or trans-10, cis-12 18:2 (conjugated linoleic acid; CLA). On d 5
      of infusion, mammary gland biopsies were performed and tissues were analyzed for
      mRNA expression of acetyl-coenzyme A carboxylase, fatty acid synthetase,
      lipoprotein lipase, SCD1, SCD5, sterol regulatory element-binding protein-1, IL6,
      IL8, and tumor necrosis factor-alpha by real-time PCR. Compared with the control
      treatment, CLA reduced milk fat concentration and yield by 46 and 38%,
      respectively, and increased the trans-10, cis-12 18:2 content in milk fat from
      0.05 to 3.54 mg/g. Milk yield, milk protein, and dry matter intake were
      unaffected by treatment. Infusion of the CLA treatment reduced the mRNA
      expression of acetyl-coenzyme A carboxylase and fatty acid synthetase by 46 and
      57%, respectively, and tended to reduce the expression of SCD1 and lipoprotein
      lipase. Abundance of mRNA for sterol regulatory element-binding protein-1 was
      reduced by 59% in the CLA treatment group. However, infusing trans-10, cis-12
      18:2 did not affect the expression of transcripts for SCD5, tumor necrosis factor
      alpha, IL6, and IL8. Results from the current study corroborate the idea that
      effects of trans-10, cis-12 18:2 reported on adipose tissue in animal models and
      humans are not part of the response in the inhibition of milk fat synthesis in
      lactating dairy cows. They also support the hypothesis that SCD1 and SCD5 present
      important differences in their regulation and physiological roles.

PMID- 19762836
TI  - Evaluation of catfish oil as a feedstuff for lactating Holstein cows.
AB  - The objective of this study was to evaluate catfish oil (CFO) as a dietary
      ingredient for lactating Holstein cows. Twelve multiparous Holstein cows (6
      fitted with a rumen cannula and 6 noncannulated cows), arranged in a 3 x 3 Latin
      square design replicated 4 times, were used to evaluate CFO as a dietary
      ingredient for lactating Holstein cows. Each period lasted 27 d with the last 13
      d used for data collection. Dietary treatments were 0, 1.5, and 3% CFO (dry
      matter basis). Orally dosing with chromium oxide powder was used as an external
      inert marker for calculation of apparent dry matter and nutrient digestion
      coefficients. Ruminal fluid was collected hourly for 8 h after feeding to measure
      pH and volatile fatty acids. Intake of dry matter increased as intake of CFO
      increased (23.0, 24.4, and 25.4 kg/d). Production of milk was unchanged by the
      feeding of CFO (29.0, 29.0, and 29.4 kg/d). Concentrations of milk fat (3.57,
      3.60, and 3.48%) and protein (3.21, 3.18, and 3.23%) were unchanged by feeding
      CFO. Concentrations of plasma glucose (57.8, 55.1, and 56.0 mg/100 mL), urea
      nitrogen (11.6, 11.0, and 12.0 mg/100 mL), and insulin (0.55, 0.53, and 0.57
      ng/mL) were not affected by dietary treatments. Average ruminal fluid pH
      decreased (6.40, 6.20, and 6.15), as did the molar proportions of acetate (64.5,
      64.2, and 63.4%), as dietary concentration of CFO increased. The molar
      proportions of propionate increased (19.4, 20.0, and 20.4%) as did that of
      butyrate (12.0, 12.4, and 12.5%) as intake of CFO increased. Ruminal protozoa
      numbers were unchanged by treatments. Apparent digestibility coefficients of dry
      matter, crude protein, neutral detergent fiber, and acid detergent fiber were
      increased by addition of CFO. In situ lag, rate, and extent of corn silage dry
      matter digestion were not affected by the inclusion of CFO. However, in situ
      digestion rate of neutral detergent fiber was increased (0.023, 0.024, and 0.029
      h(-1)) with increasing intake of CFO. In a second study involving 190 Holstein
      cows, those fed CFO at 1.8% of dietary dry matter produced 1.2 kg more milk/d
      than those not fed CFO, along with an increase in milk protein concentration.
      Catfish oil can be a viable lipid source for dairy cows when fed at up to 3% of
      the dietary dry matter.

PMID- 19762837
TI  - Influence of calcium and phosphorus feeding on markers of bone metabolism in
      transition cows.
AB  - A study was carried out to verify the effect of Ca and P levels on production,
      digestibility, and serum bone metabolism biomarkers in dairy cows. Fifty-two
      nonlactating multiparous cows (>or=3 lactations) were confined in a free-stall
      barn approximately 20 d before calving. A standard close-up diet was fed to cows
      once daily until d 2 postpartum. Cows were randomly assigned to 1 of 4 dietary
      treatments arranged in a 2 x 2 factorial approach averaging 0.64% Ca for high Ca
      (HCa), 0.46% Ca for low Ca (LCa), 0.47% P for high P (HP), and 0.38% P for low P
      (LP) on a dry matter basis. Experimental diets were fed twice daily from 3 d in
      milk (DIM) until 31 DIM. Intake and milk yield were recorded daily. Milk samples
      were collected on d 28, 29, and 30 postpartum for components analyses. Blood
      samples were drawn 10 d before expected calving, at calving, and at 15 and 30 DIM
      for serum analyses of osteocalcin, a biomarker of bone accretion, and
      pyridinoline, a biomarker of bone resorption. Total fecal collection was
      conducted when cows in a block averaged 20 DIM. Intake and production traits were
      not significantly affected by any of the dietary treatments. Cows averaged nearly
      21 kg/d dry matter intake and 44 kg/d milk yield from 6 to 31 DIM. There were no
      significant differences across treatments in body weight or body condition score
      loss. Phosphorus intake, P fecal output, P digestibility, and P apparent
      absorption were affected by dietary P content. Calcium intake was higher with
      HCa, but Ca fecal output, digestibility, and apparent absorption showed an
      interaction between dietary Ca and dietary P. Calcium fecal output was 100.6 g/d
      for cows fed HCaHP, intermediate for cows on the HCaLP diet (89 g/d), and similar
      among cows fed the 2 LCa diets (70 g/d with LCaHP and 75 with LCaLP). There was
      no significant effect of Ca or P on osteocalcin measurements. Pyridinoline
      concentrations were affected by dietary Ca levels and tended to have a
      significant dietary Ca x dietary P interaction. Phosphorus apparent digestibility
      occurred independently of dietary Ca levels. Results of this study suggest that
      more bone was mobilized in cows fed LCa diets, but excess dietary P caused
      greater and prolonged bone mobilization regardless of dietary Ca content.

PMID- 19762838
TI  - Milk fatty acids in dairy cows fed whole crude linseed, extruded linseed, or
      linseed oil, and their relationship with methane output.
AB  - This experiment studied the effect of 3 different physical forms of linseed fatty
      acids (FA) on cow dairy performance, milk FA secretion and composition, and their
      relationship with methane output. Eight multiparous, lactating Holstein cows were
      assigned to 1 of 4 dietary treatments in a replicated 4 x 4 Latin square design:
      a control diet (C) based on corn silage (59%) and concentrate (35%), and the same
      diet supplemented with whole crude linseed (CLS), extruded linseed (ELS), or
      linseed oil (LSO) at the same FA level (5% of dietary dry matter). Each
      experimental period lasted 4 wk. Dry matter intake was not modified with CLS but
      was lowered with both ELS and LSO (-3.1 and -5.1 kg/d, respectively) compared
      with C. Milk yield and milk fat content were similar for LSO and ELS but lower
      than for C and CLS (19.9 vs. 22.3 kg/d and 33.8 vs. 43.2 g/kg, on average,
      respectively). Compared with diet C, CLS changed the concentrations of a small
      number of FA; the main effects were decreases in 8:0 to 16:0 and increases in
      18:0 and cis-9 18:1. Compared with diet C (and CLS in most cases), LSO
      appreciably changed the concentrations of almost all the FA measured; the main
      effects were decreases in FA from 4:0 to 16:0 and increases in 18:0, trans-11
      16:1, all cis and trans 18:1 (except trans-11 18:1), and nonconjugated trans 18:2
      isomers. The effect of ELS was either intermediate between those of CLS and LSO
      or similar to LSO with a few significant exceptions: increases in 17:0 iso; 18:3n
      3; trans-11 18:1; cis-9, trans-11 conjugated linoleic acid; and trans-11, trans
      13 conjugated linoleic acid and a smaller increase in cis-9 18:1. The most
      positive correlations (r = 0.87 to 0.91) between milk FA concentrations and
      methane output were observed for saturated FA from 6:0 to 16:0 and for 10:1, and
      the most negative correlations (r = -0.86 to -0.90) were observed for trans
      16+cis-14 18:1; cis-9, trans-13 18:2; trans-11 16:1; and trans-12 18:1. Thus,
      milk FA profile can be considered a potential indicator of in vivo methane output
      in ruminants.

PMID- 19762839
TI  - Fatty acid intake and milk fatty acid composition of Holstein dairy cows under
      different grazing strategies: herbage mass and daily herbage allowance.
AB  - The objective of this study was to investigate the effect of level of 1)
      pregrazing herbage mass (HM) and 2) level of daily herbage allowance (DHA) on the
      performance and fatty acid (FA) composition of milk from grazing dairy cows.
      Sixty-eight Holstein-Friesian dairy cows were allocated to either a high or low
      pregrazing HM (1,700 vs. 2,400 kg of DM/ha; >40 mm), and within HM treatment,
      cows were further allocated to either a high or low DHA (16 vs. 20 kg of DM/d per
      cow; >40 mm) in a 2 x 2 factorial design. Pregrazing HM did not affect dry matter
      intake (17.5 +/- 0.75 kg/d), milk production (22.1 +/- 0.99 kg/d), milk
      composition (milk fat, 3.88 +/- 0.114%; milk protein, 3.28 +/- 0.051%), body
      weight (525 +/- 16 kg), or body condition score (2.65 +/- 0.064). Increasing DHA
      increased dry matter intake (+1.5 kg/d) but did not affect any other variable
      measured. Cows grazing the low HM or high DHA had a higher daily intake of total
      FA (+0.12 and +0.09 kg/d, respectively, for the low HM and high DHA), alpha
      linolenic acid (LNA; +0.08 and +0.05 kg/d, respectively, for the low HM and high
      DHA), and linoleic acid (+0.01 for both the low HM and high DHA) compared with
      either the high HM or low DHA. Milk conjugated linoleic acid (cis-9, trans-11
      isomer) was not affected by treatment (13.0 +/- 0.77 g/kg of total FA); however,
      large variation was recorded between individual animals (range from 5.9 to 20.6
      g/kg of total FA). Milk concentrations of LNA were higher for animals offered the
      low HM (5.3 g/kg of total FA), but across treatments, milk concentrations of LNA
      were low (4.9 +/- 0.33 g/kg of total FA). The present study indicates that
      changes in HM and DHA do not have a great effect on the milk FA composition of
      grazing dairy cows. Further enhancement of the beneficial FA content in milk
      purely from changes in grazing strategy may be difficult when pasture quality is
      already high.

PMID- 19762840
TI  - A simple urine-collecting apparatus and method for cows and heifers.
AB  - An apparatus and method that can allow continuous and precise total collection of
      urine under normal conditions was developed that could satisfy the urine-sampling
      requirement of balance studies, metabolic experiments, and hormone trials of cows
      and heifers. The apparatus is composed of an anterior urethra, a urine cup, and a
      collection barrel. Total and precise collection of urine can be achieved without
      leakage, fecal contamination, or urethra infection. The apparatus has few
      negative effects on the cows and does not influence the cows' normal
      physiological activities.

PMID- 19762841
TI  - Differences in the expression of genes involved in the somatotropic axis in
      divergent strains of Holstein-Friesian dairy cows during early and mid lactation.
AB  - Differences in genetic selection criteria for dairy cows internationally have led
      to divergence in the Holstein-Friesian breed. The objective of this study was to
      compare hepatic expression of genes of the somatotropic axis in the North
      American Holstein-Friesian and the New Zealand Holstein-Friesian strains of dairy
      cow at early and mid lactation. Mature cows of both the North American Holstein
      Friesian (n = 10) and New Zealand Holstein-Friesian (n = 10) strains were
      selected. Liver tissue was collected by percutaneous punch biopsy from all cows
      at 35 and 140 d postpartum, representing early and mid lactation, respectively.
      Total RNA was extracted and the hepatic expression of genes involved in the
      control of the somatotropic axis was examined. Abundance of insulin-like growth
      factor (IGF)-1 mRNA was greater in the New Zealand strain, concomitant with a
      tendency for increased expression of acid-labile subunit mRNA. Across strains,
      mRNA abundance of IGF-binding protein-1, IGF-binding protein-2, and growth
      hormone receptor 1A decreased from d 35 to 140 postpartum, whereas expression of
      IGF-1 and acid-labile subunit tended to increase. Abundance of suppressor of
      cytokine signaling-3 mRNA was increased at d 140 postpartum. Both the strain of
      Holstein-Friesian cow and the stage of lactation influenced expression of genes
      controlling the somatotropic axis in hepatic tissue.

PMID- 19762842
TI  - Poisson versus threshold models for genetic analysis of clinical mastitis in US
      Holsteins.
AB  - Typically, clinical mastitis is coded as the presence or absence of disease in a
      given lactation, and records are analyzed with either linear models or binary
      threshold models. Because the presence of mastitis may include cows with multiple
      episodes, there is a loss of information when counts are treated as binary
      responses. Poisson models are appropriated for random variables measured as the
      number of events, and although these models are used extensively in studying the
      epidemiology of mastitis, they have rarely been used for studying the genetic
      aspects of mastitis. Ordinal threshold models are pertinent for ordered
      categorical responses; although one can hypothesize that the number of clinical
      mastitis episodes per animal reflects a continuous underlying increase in
      mastitis susceptibility, these models have rarely been used in genetic analysis
      of mastitis. The objective of this study was to compare probit, Poisson, and
      ordinal threshold models for the genetic evaluation of US Holstein sires for
      clinical mastitis. Mastitis was measured as a binary trait or as the number of
      mastitis cases. Data from 44,908 first-parity cows recorded in on-farm herd
      management software were gathered, edited, and processed for the present study.
      The cows were daughters of 1,861 sires, distributed over 94 herds. Predictive
      ability was assessed via a 5-fold cross-validation using 2 loss functions: mean
      squared error of prediction (MSEP) as the end point and a cost difference
      function. The heritability estimates were 0.061 for mastitis measured as a binary
      trait in the probit model and 0.085 and 0.132 for the number of mastitis cases in
      the ordinal threshold and Poisson models, respectively; because of scale
      differences, only the probit and ordinal threshold models are directly
      comparable. Among healthy animals, MSEP was smallest for the probit model, and
      the cost function was smallest for the ordinal threshold model. Among diseased
      animals, MSEP and the cost function were smallest for the Poisson model, followed
      by the ordinal threshold model. In general, the models for count variables more
      accurately identified diseased animals and more accurately predicted mastitis
      costs. Healthy animals were more accurately identified by the probit model.

PMID- 19762843
TI  - Predictive ability of direct genomic values for lifetime net merit of Holstein
      sires using selected subsets of single nucleotide polymorphism markers.
AB  - The objective of the present study was to assess the predictive ability of
      subsets of single nucleotide polymorphism (SNP) markers for development of low
      cost, low-density genotyping assays in dairy cattle. Dense SNP genotypes of 4,703
      Holstein bulls were provided by the USDA Agricultural Research Service. A subset
      of 3,305 bulls born from 1952 to 1998 was used to fit various models (training
      set), and a subset of 1,398 bulls born from 1999 to 2002 was used to evaluate
      their predictive ability (testing set). After editing, data included genotypes
      for 32,518 SNP and August 2003 and April 2008 predicted transmitting abilities
      (PTA) for lifetime net merit (LNM$), the latter resulting from progeny testing.
      The Bayesian least absolute shrinkage and selection operator method was used to
      regress August 2003 PTA on marker covariates in the training set to arrive at
      estimates of marker effects and direct genomic PTA. The coefficient of
      determination (R(2)) from regressing the April 2008 progeny test PTA of bulls in
      the testing set on their August 2003 direct genomic PTA was 0.375. Subsets of
      300, 500, 750, 1,000, 1,250, 1,500, and 2,000 SNP were created by choosing
      equally spaced and highly ranked SNP, with the latter based on the absolute value
      of their estimated effects obtained from the training set. The SNP effects were
      re-estimated from the training set for each subset of SNP, and the 2008 progeny
      test PTA of bulls in the testing set were regressed on corresponding direct
      genomic PTA. The R(2) values for subsets of 300, 500, 750, 1,000, 1,250, 1,500,
      and 2,000 SNP with largest effects (evenly spaced SNP) were 0.184 (0.064), 0.236
      (0.111), 0.269 (0.190), 0.289 (0.179), 0.307 (0.228), 0.313 (0.268), and 0.322
      (0.291), respectively. These results indicate that a low-density assay comprising
      selected SNP could be a cost-effective alternative for selection decisions and
      that significant gains in predictive ability may be achieved by increasing the
      number of SNP allocated to such an assay from 300 or fewer to 1,000 or more.

PMID- 19762844
TI  - The influence of genetic selection and feed system on the reproductive
      performance of spring-calving dairy cows within future pasture-based production
      systems.
AB  - Three genetic groups of Holstein-Friesian dairy cows were established from within
      the Moorepark (Teagasc, Ireland) dairy research herd: LowNA, indicative of the
      Irish national average-genetic-merit North American Holstein-Friesian; HighNA,
      high-genetic-merit North American Holstein-Friesian; HighNZ, high-genetic-merit
      New Zealand Holstein-Friesian. Genetic merit in this study was based on the Irish
      total merit index, the Economic Breeding Index. Animals from within each genetic
      group were randomly allocated to 1 of 2 possible post-European Union-milk-quota
      pasture-based feeding systems (FS): 1) The Moorepark (MP) pasture system (2.64
      cows/ha and 500 kg of concentrate supplement per cow per lactation) and 2) a high
      output per hectare (HC) pasture system (2.85 cows/ha and 1,200 kg of concentrate
      supplement per cow per lactation). A total of 126, 128, and 140 spring-calving
      dairy cows were used during the years 2006, 2007, and 2008, respectively. Each
      group had an individual farmlet of 17 paddocks, and all groups were managed
      similarly throughout the study. The effects of genetic group, FS, and the
      interaction between genetic group and FS on reproductive performance, body
      weight, body condition score, and blood metabolite concentrations were studied
      using mixed models with factorial arrangements of genetic groups and FS. Odds
      ratios were used in the analysis of binary fertility traits, and survival
      analysis was used in the analysis of survival after first calving. When treatment
      means were compared, the HighNA and HighNZ genotypes (with greater genetic merit
      for fertility performance) had greater first-service pregnancy rates and had a
      greater proportion of cows pregnant after 42 d of the breeding season than the
      LowNA group. Both HighNA and HighNZ genotypes were submitted for artificial
      insemination earlier in the breeding season and had greater survival than the
      LowNA genotype. There was no significant FS or genotype by FS interactions for
      any of the reproductive, blood metabolite, body weight, or body condition score
      measures. The results demonstrate that increased genetic merit for fertility
      traits resulted in improved reproductive performance and that the poor
      reproductive capacity of inferior-genetic-merit animals for fertility was not
      improved through concentrate supplementation at pasture.

PMID- 19762845
TI  - Selection response for milk production in conventional production systems in
      Mexico, using genetic evaluations of Holstein sires from Canada and the United
      States.
AB  - Polynomial regression models of the first, second, and third order were used to
      fit milk production deviations of daughters in Mexico on Canadian and US
      predicted transmitting ability values for 305-d mature-equivalent milk production
      (kg). For the pairs Canada-Mexico and Mexico-United States, 40 and 73 bulls with
      a minimum reliability of 0.75 were analyzed, respectively. Genetic correlations
      between pairs of countries were also estimated. The parameters were evaluated for
      all data, and for sires grouped according to the mean of the average phenotypic
      milk production (high and low) of their daughters' herd mates. Quadratic and
      cubic effects were not significant in any analysis. From linear regression
      models, slopes of Mexican daughter deviations on US and Canadian predicted
      transmitting abilities were 1.01 and 0.93, respectively. Slopes were greater but
      intercepts were smaller for the high versus low level of production of the sires'
      herd mates in Mexico. A greater difference between the genetic correlations was
      found for the high versus low environmental level than for the low level (0.79
      vs. 0.70) for Mexico-US data compared with Canada-Mexico data (0.81 vs. 0.78).
      Genetic correlations between Mexico and the United States (0.74), and between
      Mexico and Canada (0.77), were smaller than the genetic correlation between the
      same Canadian and US sires (0.92), suggesting the presence of a moderate degree
      of genotype-environment interaction for milk production between Canada and the
      United States, and Mexico.

PMID- 19762846
TI  - Bovine Muc1 is a highly polymorphic gene encoding an extensively glycosylated
      mucin that binds bacteria.
AB  - The bovine Muc1 protein is synthesized by mammary epithelial cells and shed into
      milk as an integral component of the milk fat globule membrane; however, the
      structure and functions of this mucin, particularly in relation to lactation, are
      poorly defined. The objectives of this investigation were to investigate the Muc1
      gene and protein structures in the context of lactation and to test the
      hypothesis that Muc1 has a role in innate immune defense. Polymerase chain
      reaction analysis of genomic DNA from 630 cattle revealed extensive polymorphism
      in the variable number of tandem repeats (VNTR) in the bovine Muc1 gene. Nine
      allelic variants spanning 7 to 23 VNTR units, each encoding 20 AA, were
      identified. Three alleles, containing 11, 14, and 16 VNTR units, respectively,
      were predominant. In addition, a polymorphism in one of the VNTR units has the
      potential to introduce a unique site for N-linked glycosylation. Statistical
      analysis indicated weak associations between the VNTR alleles and milk protein
      and fat percentages in a progeny-tested population of Holstein-Friesian dairy
      cattle. No association with somatic cell count could be demonstrated. Bovine Muc1
      was purified from milk fat globule membranes and characterized. The protein was
      highly glycosylated, primarily with O-linked sialylated T-antigen [Neu5Ac(alpha2
      3)-Gal(beta1-3)-GalNAcalpha1] and, to a lesser extent, with N-linked
      oligosaccharides, which together accounted for approximately 60% of the apparent
      mass of Muc1. Purified bovine Muc1 directly bound fluorescently labeled
      Escherichia coli BioParticles (Invitrogen, Mount Waverley, Australia) and
      inhibited their binding to bovine mammary epithelial cells grown in vitro. It was
      also demonstrated that the expression of Muc1 mRNA in bovine mammary epithelial
      cells was markedly upregulated by lipopolysaccharide. Muc1 may be a pattern
      recognition protein that has the capacity to sequester bacteria and prevent their
      attachment to epithelial surfaces by immobilizing and subsequently shedding Muc1
      bound bacteria from the cell surface. It was concluded that bovine Muc1 is
      probably an inducible innate immune effector and an important component of the
      first line of defense against bacterial invasion of epithelial surfaces,
      particularly mammary epithelial surfaces and the neonatal gut.

PMID- 19762847
TI  - Application of selection index calculations to determine selection strategies in
      genomic breeding programs.
AB  - The availability of genomic estimated breeding values (GEBV) allows for possible
      modifications to existing dairy cattle breeding programs. Selection index
      calculations including genomic and phenotypic observations as index sources were
      used to determine the optimal number of offspring per genotyped sire with a focus
      on functional traits and the design of cooperator herds, and to evaluate the
      importance of a central station test for genotyped bull dams. Evaluation criteria
      to compare different breeding strategies were correlations between index and
      aggregate genotype (r(TI)), and the relative selection response percentage (RSR)
      of an index without single nucleotide polymorphism information in relation to a
      single nucleotide polymorphism-based index. The number of required daughter
      records per sire to achieve a predefined r(TI) strongly depends on the accuracy
      of GEBV (r(mg)) and the heritability of the trait. For a desired r(TI) of 0.8,
      h(2) = 0.10, and r(mg) = 0.5, at least 57 additional daughters have to be
      included in the genetic evaluation. Daughter records of genotyped sires are not
      necessary for optimal scenarios where r(mg) is greater than or equal to r(TI).
      There still is a substantial need for phenotypic daughter records, especially for
      low-heritability functional traits and r(mg) < 0.7. Phenotypic records from
      genotyped potential bull dams have no relevance for increasing r(TI), even with a
      low value for r(mg) of 0.5. Hence, genomic breeding programs should focus on
      recording functional traits within progeny groups, preferably in cooperator
      herds. For low-heritability traits and with r(mg) > 0.7, the RSR of conventional
      breeding programs was only 10% of RSR from genomic breeding strategies. As shown
      in scenarios including 2 traits in the index as well as in the aggregate
      genotype, the availability of highly accurate GEBV for production traits and low
      accuracy GEBV for functional traits increased the risk of widening the gap
      between selection responses in production and functionality. Counteractions are
      possible, such as via higher economic weights for low-heritability functional
      traits. Finally, an alternative selection strategy considering only 2 pathways of
      selection for genotyped male calves and for cow dams was evaluated. This strategy
      is competitive with a 4-pathway genomic breeding program if the fraction of
      selected male calves for the artificial insemination program is below 1% and if
      selection is focused on functionality, thus pointing to substantial
      insufficiencies caused by low reliabilities of breeding values for cows for such
      traits in conventional bull dam selection schemes.

PMID- 19762848
TI  - Mid-infrared spectroscopy predictions as indicator traits in breeding programs
      for enhanced coagulation properties of milk.
AB  - The aims of this study were to investigate variation of milk coagulation property
      (MCP) measures and their predictions obtained by mid-infrared spectroscopy (MIR),
      to investigate the genetic relationship between measures of MCP and MIR
      predictions, and to estimate the expected response from a breeding program
      focusing on the enhancement of MCP using MIR predictions as indicator traits.
      Individual milk samples were collected from 1,200 Brown Swiss cows (progeny of 50
      artificial insemination sires) reared in 30 herds located in northern Italy.
      Rennet coagulation time (RCT, min) and curd firmness (a(30), mm) were measured
      using a computerized renneting meter. The MIR data were recorded over the
      spectral range of 4,000 to 900 cm(-1). Prediction models for RCT and a(30) based
      on MIR spectra were developed using partial least squares regression. A cross
      validation procedure was carried out. The procedure involved the partition of
      available data into 2 subsets: a calibration subset and a test subset. The
      calibration subset was used to develop a calibration equation able to predict
      individual MCP phenotypes using MIR spectra. The test subset was used to validate
      the calibration equation and to estimate heritabilities and genetic correlations
      for measured MCP and their predictions obtained from MIR spectra and the
      calibration equation. Point estimates of heritability ranged from 0.30 to 0.34
      and from 0.22 to 0.24 for RCT and a(30), respectively. Heritability estimates for
      MCP predictions were larger than those obtained for measured MCP. Estimated
      genetic correlations between measures and predictions of RCT were very high and
      ranged from 0.91 to 0.96. Estimates of the genetic correlation between measures
      and predictions of a(30) were large and ranged from 0.71 to 0.87. Predictions of
      MCP provided by MIR techniques can be proposed as indicator traits for the
      genetic enhancement of MCP. The expected response of RCT and a(30) ensured by the
      selection using MIR predictions as indicator traits was equal to or slightly less
      than the response achievable through a single measurement of these traits.
      Breeding strategies for the enhancement of MCP based on MIR predictions as
      indicator traits could be easily and immediately implemented for dairy cattle
      populations where routine acquisition of spectra from individual milk samples is
      already performed.

PMID- 19762849
TI  - Use of test-day records beyond three hundred five days for estimation of three
      hundred five-day breeding values for production traits and somatic cell score of
      Canadian Holsteins.
AB  - The Canadian Test-Day Model includes test-day (TD) records from 5 to 305 d in
      milk (DIM). Because 60% of Canadian Holstein cows have at least one lactation
      longer than 305 d, a significant number of TD records beyond 305 DIM could be
      included in the genetic evaluation. The aim of this study was to investigate
      whether TD records beyond 305 DIM could be useful for estimation of 305-d
      estimated breeding value (EBV) for milk, fat, and protein yields and somatic cell
      score. Data were 48,638,184 TD milk, fat, and protein yields and somatic cell
      scores from the first 3 lactations of 2,826,456 Canadian Holstein cows. All
      production traits were preadjusted for the effect of pregnancy. Subsets of data
      were created for variance-component estimation by random sampling of 50 herds.
      Variance components were estimated using Gibbs sampling. Full data sets were used
      for estimation of breeding values. Three multiple-trait, multiple-lactation
      random regression models with TD records up to 305 DIM (M305), 335 DIM (M335),
      and 365 DIM (M365) were fitted. Two additional models (M305a and M305b) used TD
      records up to 305 DIM and variance components previously estimated by M335 and
      M365, respectively. The effects common to all models were fixed effects of herd x
      test-date and DIM class, fixed regression on DIM nested within region x age x
      season class, and random regressions for additive genetic and permanent
      environmental effects. Legendre polynomials of order 6 and 4 were fitted for
      fixed and random regressions, respectively. Rapid increase of additive genetic
      and permanent environmental variances at extremes of lactations was observed with
      all 3 models. The increase of additive genetic and permanent environmental
      variances was at earlier DIM with M305, resulting in greater variances at 305 DIM
      with M305 than with M335 and M365. Model M305 had the best ability to predict TD
      yields from 5 through 305 DIM and less error of prediction of 305-d EBV than M335
      and M365. Model M335 had smaller change of 305-d EBV of bulls over the period of
      7 yr than did M305 and M365. Model M305a had the least error of prediction and
      change of 305-d EBV from all models. Therefore, the use of TD records of Holstein
      cows from 5 through 305 DIM and variance components estimated using records up to
      335 DIM is recommended for the Canadian Test-Day Model.

PMID- 19762850
TI  - Evaluation of the University of Minnesota Tri-plate and 3M Petrifilm for the
      isolation of Staphylococcus aureus and Streptococcus species from clinically
      mastitic milk samples.
AB  - The primary objective was to compare microbiological results of the University of
      Minnesota Tri-plate and the 3M Petrifilm Staph Express (STX) Count Plate to
      standard culture techniques for identification of clinical mastitis caused by
      Staphylococcus aureus. The secondary objective was to evaluate the Tri-plate's
      ability to differentiate Streptococcus spp. from other gram-positive organisms.
      The tests were evaluated using clinically positive mastitic milk samples (n =
      282) to determine their ability to diagnose the pathogens of interest. A Tri
      plate was classified positive for Staph. aureus when at least 1 colony exhibiting
      beta-hemolysis was present on the Factor media portion of the plate. When the
      plate was used in this manner and read by a trained laboratory technician, the
      sensitivity of the Tri-plate was 97.9% and the specificity was 81.8%. When the
      Tri-plate was evaluated by the laboratory technician for its ability to diagnose
      Streptococcus spp., both sensitivity and specificity of the test were very good
      (92.6 and 89.5%, respectively). Using the Petrifilm, samples were classified as
      positive for Staph. aureus if any red-violet colonies were present on the
      Petrifilm after an initial 24-h incubation. When used in this manner, the
      Petrifilm had a sensitivity of 97.4% and a specificity of 76.1%. Further
      evaluation of the Petrifilm was done using the STX disk, which was used to
      confirm the presence of Staph. aureus. When using the presence of 1 pink colony
      on the disk, the sensitivity of the Petrifilm was 92.1% and the specificity was
      93.1%. Both the Tri-plate and the 3M STX Petrifilm successfully diagnosed Staph.
      aureus in clinical milk samples when used in a laboratory setting and the Tri
      plate successfully differentiated Streptococcus spp. from other gram-positive
      organisms.

PMID- 19762851
TI  - Editorial: partnerships--whether to ride the wave to success or to slowly sink
      and perhaps be lost?

PMID- 19762852
TI  - Effects of group size and repeated social disruption on the serotonergic and
      dopaminergic systems in two genetic lines of White Leghorn laying hens.
AB  - Farm practices such as increasing group size (GS) and mixing unfamiliar chickens
      may result in repeated social disruption (RSD) and affect the well-being of hens.
      To examine whether there are genetic differences in response to social stress, 2
      genetic strains of White Leghorn hens were used [i.e., high group production and
      survivability (HGPS) and DeKalb XL commercial strain (DXL). At 50 wk of age,
      social stress was created by increasing GS from 4 hens (control) to 8 hens
      (experimental) per cage and removing hens within the stressed groups to create 4
      treatments (control-HGPS, control-DXL, GS/RSD-HGPS, and GS/RSD-DXL). For RSD, 2
      hens per cage were moved weekly among the experimental cages within the same
      treatment. At 58 wk of age, blood sample and brain were collected from 1 hen per
      cage (n=10 per treatment). Whole-blood tryptophan and serotonin (5-HT) and plasma
      norepinephrine (NE), epinephrine (EP), and dopamine (DA) were analyzed by HPLC.
      The raphe nuclei and the hypothalamus (HYP) were dissected and analyzed by HPLC
      for the central NE, EP, DA, dihydroxyphenylacetic acid (DOPAC), homovanillic
      acid, 5-hydroxyindoleacetic acid (5-HIAA), 5-HT, and the ratios of DOPAC:DA and 5
      HIAA:5-HT. There were no line differences in the concentrations of peripheral
      tryptophan, 5-HT, EP, NE, and DA in response to GS-RSD (P>0.10). However,
      neuronal transmitters were regulated differently in the different central nuclei
      between the lines. In the raphe nuclei, control-HGPS tended to have a higher 5
      HIAA:5-HT ratio than the control-DXL (P=0.09). Concentrations of EP were
      increased in the DXL hens (P<0.01), whereas the HGPS hens had decreased levels of
      DOPAC (P<0.05) and DA turnover (DOPAC:DA, P<0.01) post GS-RSD. In the HYP,
      compared with relative controls, there were no significant differences in the
      concentrations of 5-HT, whereas the levels of 5-HIAA were reduced (P<0.01) after
      GS-RSD, suggesting that GS-RSD led to a lower 5-HT turnover in the HYP. The
      results indicate that selection for docility and productivity alters serotonergic
      and catecholamine homeostasis in hens in response to social stress, GS-RSD.

PMID- 19762853
TI  - Utilizing fungus myceliated grain for molt induction and performance in
      commercial laying hens.
AB  - Molting in poultry is used to rejuvenate hens for a second or third laying cycle.
      Feed withdrawal was once the most effective method used for molt induction;
      however, it has being phased out due to food safety and animal welfare concerns.
      This study evaluated the utilization of fungus myceliated grain as a safe and
      effective alternative for inducing molt, enhancing immunity, reducing Salmonella
      growth, and returning to egg production. Laying hens were subjected to 1 of 5
      treatments: 1) nonfed (NF), 2) full-fed (FF), 3) fungus myceliated meal (FM), 4)
      90% fungus myceliated meal+10% standard layer ration (FM-90), and 5) 90% alfalfa
      meal+10% fungus myceliated meal (AF-90). Each treatment condition was replicated
      9 times during a 9-d molt period. The results revealed that egg production for
      treatments 1 and 3 ceased completely by d 5, whereas hens in treatments 4 and 5
      ceased egg production by d 6. The percentage of BW loss decreased significantly
      (P<0.05) in treatments 1 (57%), 2 (8%), 3 (35%), 4 (37%), and 5 (44%). Ovary
      weights of hens fed all molting diets decreased significantly from the full-fed
      control but did not differ significantly (P<0.05) from each other. Salmonella
      population in the crop, ovary, and ceca from hens differed significantly (P<0.05)
      among treatments. Return to egg production differed between treatments with
      higher production beginning in treatment 3 and ending in treatment 5. Antibody
      titers did differ (P<0.05) among treatments. From these results, fungus
      myceliated meal appears to be a viable alternative to conventional feed
      withdrawal and other methods for the successful induction of molt and retention
      of postmolt performance.

PMID- 19762854
TI  - Transport stress in broilers: I. Blood metabolism, glycolytic potential, and meat
      quality.
AB  - The effect of transport stress on blood metabolism, glycolytic potential, and
      meat quality in broilers was investigated. Arbor Acres chicks (n = 360, 1 d old,
      males) were randomly allotted to 1 of 5 treatments: unstressed control, 45-min
      (short-term) transport with 45-min (short-term) recovery, 45-min transport with 3
      h (long-term) recovery; 3 h (long-term) transport with 45-min recovery, and 3-h
      transport with 3-h recovery. Each treatment consisted of 6 replicates with 12
      birds each. On d 46, all birds (except the control group) were transported
      according to a designed protocol. Transport time affected plasma glucose level
      (P<0.05) and glycogen level (P=0.06) in breast muscle as well as the area
      (P<0.01) and density (P<0.01) of IIa fibers. Glucose concentration increased
      slightly during the first 45 min of transport and then decreased dramatically in
      the long-term transported broilers (P<0.05). Long-term transport decreased the
      concentration of breast glycogen (P=0.06) and affected the size of IIa fibers in
      tibialis anterior by decreasing the area (P<0.01) with an increase in density
      (P<0.01). However, a long-term recovery after transport contributed to the
      homeostasis of blood corticosterone (CORT, P=0.05) and low levels of glycogen
      (P<0.05), lactate (P<0.01), and glycolytic potential (P<0.01) in thigh muscles.
      Interactions existed between transport and recovery time on area (P<0.05) and
      density (P<0.01) of IIa fibers. Furthermore, plasma nonesterified fatty acids
      increased significantly in the 3-h transport with 3-h recovery group (P<0.05) in
      comparison with the control. These results suggested that transport induced the
      release of plasma CORT and glycopenia, which affected the contractive status of
      muscle fibers by changing their area and density, and enhanced glycolysis and
      even lipolysis. A long-term recovery after transport was beneficial in lowering
      plasma CORT levels and reducing muscle glycolysis, which might improve broiler
      meat quality.

PMID- 19762855
TI  - Comparative effects of furnished and battery cages on egg production and
      physiological parameters in White Leghorn hens.
AB  - Laboratory animal well-being can be improved by housing the animals in species
      specific natural or near-to-natural environments. An enriched environment may
      have a similar effect on chickens. The purpose of this study was to examine if
      housing environment (furnished cages vs. battery cages) effects the well-being of
      laying hens. One hundred ninety-two 1-d-old non-beak-trimmed White Leghorn W-36
      chicks were reared and randomly assigned into battery cages or furnished cages at
      19 wk of age. The furnished cages had wire floors and solid metal walls, with
      perches, a dustbathing area, scratch pads, and a nestbox area with concealment
      curtain. Ten hens were housed per cage, providing a stocking density of 610 cm2
      of floor space per hen. The battery cages were commercial wire cages containing 6
      birds per cage, providing 645 cm2 of floor space per hen. Body weight and egg
      production were calculated from 25 to 60 wk of age. The peripheral concentrations
      of dopamine, epinephrine, norepinephrine, serotonin, corticosterone, and IgG were
      analyzed at 30, 40, 50, and 60 wk of age. Compared with the hens housed in the
      battery cages, the hens housed in the furnished cages were significantly heavier
      from 30 to 60 wk of age (P<0.05 and 0.01, respectively) and produced more eggs at
      40 wk of age (P<0.05). There were no treatment effects on eggshell thickness
      (P>0.05). The concentrations of serotonin were reduced, whereas corticosterone
      was increased from 50 to 60 wk of age in the hens housed in the battery cages
      (P<0.05) but not in those housed in the furnished cages, which may indicate that
      the hens housed in the battery cages were stressed. Although further studies
      remain to be completed, the present results suggest that furnished cages may be a
      favorable alternative for housing laying hens.

PMID- 19762856
TI  - Analysis of severe feather pecking behavior in a high feather pecking selection
      line.
AB  - Even though feather pecking (FP) in laying hens has been extensively studied, a
      good solution to prevent chickens from this behavior under commercial
      circumstances has not been found. Selection against FP behavior is possible, but
      for a more effective selection across different populations, it is necessary to
      characterize the genetic mechanism associated with this behavior. In this study,
      we use a high FP selection line, which has been selected for 8 generations. We
      present evidence of the presence of a major dominant allele affecting the FP
      behavior by using an argument based on the presence of mixture in the
      distribution of the observed FP and by studying the evolution of the proportion
      of very high FP along the sequence of 8 generations. This hypothesis is further
      supported by the fact that the gene transcription profile of the birds performing
      high FP differs from the profile of the other birds performing FP (456 genes
      differentially expressed from a total of 14,077 investigated genes).

PMID- 19762857
TI  - Breeding to reduce susceptibility to Escherichia coli in layers.
AB  - Colibacillosis is a bacterial disease of great concern in the layer industry
      causing substantial animal and economic losses worldwide. Breeding for resistance
      to colibacillosis is an important control strategy that would complement
      traditional management strategies such as vaccinations and therapeutic
      treatments. Because antibiotic use in animal production is expected to
      substantially decrease in the future to meet not only consumer demands but also
      regulations, it is expected that bacterial diseases such as colibacillosis will
      become even more important. A challenge test was carried out on 353 pedigreed
      White Leghorn female chickens of 1 pure line. The birds were inoculated with
      Escherichia coli at an age of 93 to 95 wk (3 hatches) and symptoms of disease and
      mortality were constantly monitored for up to 6 d after inoculation. The
      cumulative mortality was 64%, the majority of which took place in the first 2 d.
      In the present study, genetic parameters of resistance to colibacillosis were
      estimated to judge the value of genetic selection. The heritability for survival
      rate was 0.17+/-0.07. Both for quantitative as well as for qualitative traits of
      economic interest, there was no remarkable difference between survivors and hens
      that died. Data showed that it is in principle possible to breed for
      colibacillosis resistance without penalizing the improvement in other key traits.
      The B21 marker for MHC in this study was associated with a lower colibacillosis
      susceptibility. In this study, it was demonstrated that it is possible to breed
      for Escherichia coli resistance. However, due to the inconveniences of a
      challenge test, it would be very interesting to make use of MAS.

PMID- 19762858
TI  - Serum ovotransferrin as a biomarker of inflammatory diseases in chickens.
AB  - Infectious and metabolic disorders are common in poultry and cause stress, poor
      performance, and mortality that results in considerable economic loss.
      Identifying the nature of stress in chickens will assist the development of
      appropriate measures to improve health and welfare. Acute phase proteins are
      hepatic proteins, the blood concentrations of which change significantly in the
      event of many health problems including inflammation and physical injuries. Thus,
      acute phase proteins are used as nonspecific diagnostic markers for various
      health disorders. Our previous studies showed that serum ovotransferrin (OVT) is
      an acute phase protein in chickens. Therefore, in the present study, we
      investigated whether OVT concentration can be a marker of physiological stress
      using sera from chickens with different infectious and metabolic disorders. A
      competitive enzyme immunoassay was developed to measure serum OVT concentrations.
      The results show that with experimentally induced pulmonary hypertension syndrome
      and tibial dyschondroplasia, there were no significant changes in OVT levels
      compared with matched controls. In contrast, when chickens were infected with
      microbes such as the bacterium Escherichia coli, or protozoan parasites such as
      Eimeria maxima and Eimeria tenella, there was a significant increase in the
      levels of OVT in the serum. Chickens with spontaneous autoimmune vitiligo also
      showed a significant increase in blood OVT levels. These studies suggest that
      blood OVT concentration is modulated under inflammatory and microbial stress and
      can therefore be used as a diagnostic marker of infection and inflammation in
      chickens.

PMID- 19762859
TI  - Efficacy of multistrain direct-fed microbial and phytogenetic products in
      reducing necrotic enteritis in commercial broilers.
AB  - Our laboratory is evaluating the efficacy of direct-fed microbials (DFM) and
      phytogenic products to control Clostridium perfringens, a gram-positive organism
      associated with decreased performance and morbidity and mortality associated with
      necrotic enteritis, as well as some recent human food safety issues. Three
      experiments were conducted to evaluate a DFM (PoultryStar) and a phytogenic
      product (PEP125), which were administered to birds from day of hatch until
      termination (d 25) via the drinking water or through supplementation to a wheat
      corn diet, respectively. Each experiment contained a nonchallenged negative
      control and a positive control wherein birds were immunocompromised with a 10x
      dosage of infectious bursal disease vaccine at 14 d of age and subsequently
      gavaged with C. perfringens (10(7) cfu/mL) daily for 3 consecutive days starting
      on d 17. Intestinal lesions, mortality, and log10 values of C. perfringens in the
      probiotic and phytogenic treatment groups were found to be lower (P<0.05) than
      those observed in the positive controls. These experiments suggest that the DFM
      and the phytogenic product could be used as potential alternatives to help
      control C. perfringens and necrotic enteritis.

PMID- 19762860
TI  - Effects of feed supplementation with specific hen egg yolk antibody (immunoglobin
      Y) on Salmonella species cecal colonization and growth performances of challenged
      broiler chickens.
AB  - Anti-Salmonella spp. egg yolk antibodies (IgY) simultaneously directed against
      Salmonella Enteritidis and Salmonella Typhimurium were tested to determine if
      their inclusion in feed decreased Salmonella spp. cecal colonization in
      experimentally infected broiler chickens. Egg yolk powder (EYP) was obtained by
      freeze-drying egg yolks containing anti-Salmonella spp. Immunoglobin Y was
      included in feed at 5 levels of concentration (0 to 5%). Feeds were formulated to
      similar nutrient levels and provided for ad libitum intake from d 1 to 28. Three
      days after initiation of feed treatments (d 4), chickens were co-challenged with
      equal numbers of Salmonella Enteritidis and Salmonella Typhimurium (2x10(6)
      cfu/bird). Cecal samples were recovered weekly over the experimental period (d 7
      to 28) to enumerate Salmonella spp. The effect of anti-Salmonella spp. IgY feed
      supplementation on growth performance of infected chickens was also evaluated
      during the same period. In comparison with the positive control treatment (PC),
      treatments involving EYP (T1, T2, T3, T4, and T5), whether containing anti
      Salmonella spp. IgY or not, significantly improved (P<0.05) the growth
      performance of challenged chickens, but without reaching the performance levels
      of nonchallenged chickens (NC1 and NC2). However, no link can be established
      between the enhancement in growth performance of challenged birds and their
      contamination levels by Salmonella because in-feed incorporation of EYP had no
      significant effect on cecal colonization by Salmonella. Furthermore, the
      comparison of the 5 anti-Salmonella spp. IgY concentration levels in feed did not
      reveal any anti-Salmonella spp. IgY concentration effect on growth performance
      and Salmonella cecal colonization. These results suggest that anti-Salmonella
      spp. IgY would undergo denaturation and degradation after their passage through
      the animal gastrointestinal tract and reveal that components of EYP other than
      specific antibodies have a beneficial effect on growth performance.

PMID- 19762861
TI  - Effect of multiple- and single-day enrofloxacin medications against dual
      experimental infection with avian pneumovirus and Escherichia coli in turkeys.
AB  - Escherichia coli infections are a common cause of respiratory disease in turkeys.
      To control these respiratory infections in turkeys, drinking water treatment with
      enrofloxacin is widely used. The current treatment schedule advises a 5-d
      treatment at 10 mg/kg of BW. Because enrofloxacin exerts a concentration
      dependent activity, it might be useful to provide this 50 mg/kg total dose in a
      single-day treatment regimen. Therefore, we assessed whether a single-day
      treatment schedule with 50 mg/kg of BW was clinically equivalent to the advised
      multiple-day treatment schedule with 10 mg/kg of BW for 5 d. For this purpose, 3
      groups of seventeen 22-d-old turkeys were experimentally inoculated with avian
      metapneumovirus and 3 d later with E. coli. One group received 10 mg of
      enrofloxacin/kg of BW in the drinking water for 5 successive days. The second
      group received 50 mg of enrofloxacin/kg of BW for 20 h in the drinking water. The
      third group was enclosed as an untreated positive control group. Both the
      multiple- and the single-day enrofloxacin treatment regimens reduced E. coli
      multiplication in the respiratory tract tissues (turbinates, trachea and lung),
      but the 5-d treatment with 10 mg of enrofloxacin/kg in turkeys provided the best
      results by shortening the course of clinical disease, by eliminating E. coli from
      the respiratory tract without remultiplication, and by reducing macroscopic
      lesions. The efficacy of the single-day treatment did not equal that of the 5-d
      treatment, possibly by not eliminating E. coli from the respiratory organs, which
      made it possible for the remaining bacteria to reemerge in those organs. None of
      the used treatment regimens promoted the selection of bacterial clones with
      reduced susceptibility or resistance.

PMID- 19762862
TI  - Effects of different levels of vitamin E on growth performance and immune
      responses of broilers under heat stress.
AB  - This experiment was undertaken to evaluate the effect of dietary vitamin E on
      growth performance and immune response of broilers under heat stress (HS). Birds
      raised in either a thermoneutral (23.9 degrees C constant) or HS (23.9 to 38
      degrees C cycling) environment were fed a corn-soybean meal basal diet
      supplemented with vitamin E at 0, 100, or 200 mg/kg, respectively. Two hundred
      forty 1-d-old male broiler chicks were randomly assigned to 6 groups; each group
      had 4 replicates of 10 birds. Humoral immunity was assessed by i.v. injection of
      7% SRBC followed by evaluation of serum for antibody titers in primary and
      secondary responses. Cell-mediated immunity was assessed by using a Sephadex
      stimulation method to recruit abdominal exudate cells (AEC) to evaluate
      macrophage phagocytic ability. Body weight and feed intake were not significantly
      influenced by dietary vitamin E (P>0.05), whereas feed conversion was
      significantly affected by vitamin E at 100 mg/kg (P<0.05). Heat stress
      significantly reduced BW, feed intake, and feed conversion (P<0.05). Numbers of
      AEC, percentage of macrophages in AEC, phagocytic macrophages, and internalized
      opsonized and unopsonized SRBC were increased by dietary vitamin E (P<0.05). Both
      primary and secondary antibody responses were significantly increased by dietary
      vitamin E when birds were exposed to HS (P<0.05). Lymphoid organ weights,
      antibody responses, incidence of macrophages in AEC, and phagocytic ability of
      macrophages were all significantly reduced under HS. These results indicated that
      HS severely reduced growth performance and immune response of broilers, whereas
      the immune response of broilers could be improved by dietary vitamin E
      supplementation under HS.

PMID- 19762863
TI  - The cereal type in feed influences Salmonella Enteritidis colonization in
      broilers.
AB  - A study was conducted to analyze the effect of the cereal type in the diet on the
      susceptibility for Salmonella Enteritidis in broilers. In the first experiment,
      40 newly hatched broiler chicks were randomly assigned to 4 different
      experimental treatment groups. Two treatment groups were fed a maize-soybean
      based diet, of which one contained 100 mg/kg of the antibiotic growth promoter
      zinc bacitracin. The 2 other treatment groups were fed a wheat/rye-soybean-based
      diet, of which one was supplemented with 100 mg/kg of zinc bacitracin. The
      broilers were inoculated with Salmonella Enteritidis at d 11 and killed at d 15.
      When the nonantibiotic- and the antibiotic-treated birds were pooled, the
      Salmonella colonization in the spleen and ceca of the birds fed a maize-based
      diet was significantly lower in comparison to colonization of spleen and ceca in
      the wheat/rye groups. Zinc bacitracin did not affect Salmonella colonization. In
      a second experiment, which was a modified repetition of the first experiment, 120
      newly hatched broiler chicks were randomly assigned to 2 experimental treatments.
      They were fed a maize-soybean or a wheat/rye-soybean based diet, inoculated with
      Salmonella Enteritidis at d 11, and killed at d 15. A significantly lower
      Salmonella colonization was observed in the spleen, liver, and ceca of broilers
      given a maize-based diet in comparison to those given a wheat/rye-based diet.
      These data show that the cereal type in broiler feed can affect Salmonella
      colonization probably due to changes in intestinal health of the birds. Hence,
      altering the diet composition can be regarded as a simple tool to supplement
      other control measures against Salmonella in broilers.

PMID- 19762864
TI  - Enterobacteriaceae and related organisms isolated from nest run cart shelves in
      commercial shell egg processing facilities.
AB  - Enterobacteriaceae, including Salmonella, may be recovered from foods and
      processing facilities. High levels of Enterobacteriaceae in the processing plant
      environment can be an indication of inadequate sanitation. This experiment was
      designed to determine if nest run egg carts serve as reservoirs for
      Enterobacteriaceae. Eggs that are produced by hens not housed in buildings
      connected to the processing plant are referred to as nest run. Many of these eggs
      are transported to the plant on carts to be processed. Two plants in the
      southeastern United States were sampled. On each of 3 visits, 5 shelves on each
      of 5 carts were sampled (n=25/visit). A 12x12 cm area on each shelf was swabbed
      with a sterile gauze pad moistened with PBS and transported on ice back to the
      laboratory. Enterobacteriaceae were enumerated using violet red bile glucose agar
      incubated at 37 degrees C for 24 h. There was 100% prevalence for
      Enterobacteriaceae at plant A with an average 3.8 log10 cfu/mL swab diluent.
      Plant B had 90% prevalence for Enterobacteriaceae with an average 3.2 log10
      cfu/mL swab diluent. Two randomly selected isolates from each positive sample
      were recultured 3 times to increase the likelihood of clonality and were then
      identified biochemically. Of the 124 isolates analyzed, genera identified were
      Citrobacter spp., Escherichia spp., Enterobacter spp., Klebsiella spp., Hafnia
      spp., Kluyvera spp., Leclercia spp., and Salmonella spp. Pseudomonas spp. was the
      only non-Enterobacteriaceae identified by our methods. This work demonstrates
      that nest run egg carts serve as reservoirs for Enterobacteriaceae in the shell
      egg processing environment.

PMID- 19762865
TI  - Assessment of humoral and cellular-mediated immune response in chickens treated
      with tilmicosin, florfenicol, or enrofloxacin at the time of Newcastle disease
      vaccination.
AB  - The effect of tilmicosin, florfenicol, or enrofloxacin on humoral and cell
      mediated immune response induced by Newcastle disease (ND) vaccination was
      evaluated in 20-wk-old specific-pathogen-free layer chickens. Humoral immunity
      was measured by detection of ND virus (NDV) antibody titer and anti-NDV IgG
      response using the hemagglutination inhibition (HI) test and ELISA, respectively,
      whereas cell-mediated immunity was evaluated by measurement of chicken interferon
      gamma (ChIFN-gamma) produced in splenocytes cell culture stimulated with
      concanavalin A, inactivated NDV antigen, or live attenuated La Sota strain using
      ELISA. Florfenicol hampered the ND antibody production measured by both HI and
      ELISA. Tilmicosin and enrofloxacin reduced the production of ND antibody in the
      first 3 wk after the last ND vaccination measured by HI test, which suggests that
      these antibiotics exert their effect mainly on the IgM isotype. The ND
      vaccinated, but not treated group, showed an increase in ChIFN-gamma production
      after NDV antigen-specific stimulation above the nonstimulated cell culture,
      whereas this effect was masked in all the antibiotic-treated groups due to the
      stronger ChIFN-gamma production background value reported in the nonstimulated
      cell culture. In conclusion, our results showed, for the first time, that
      tilmicosin, florfenicol, or enrofloxacin reduced the humoral immune response and
      had beneficial effects on the cell-mediated immune response. In addition, we
      demonstrated that the combination of both inactivated and attenuated ND vaccine
      gave a strong immune response at both the humoral and cellular level.

PMID- 19762866
TI  - Genistein supplementation to the quail: effects on egg production and egg yolk
      genistein, daidzein, and lipid peroxidation levels.
AB  - Genistein, a soy phytoestrogen, is a powerful antioxidant. In the present study,
      we investigated the effects of dietary genistein supplementation on Japanese
      quail (Coturnix coturnix japonica) laying performance and egg yolk contents of
      malondialdehyde (MDA), vitamin A, and vitamin E. Malondialdehyde is an indicator
      of lipid peroxidation, whereas vitamins A and E have antioxidant properties.
      Birds (n=150; 5 wk old) were randomly assigned to 1 of 3 groups consisting of 50
      birds (5 replicates of 10) and were fed a basal diet or the basal diet
      supplemented with either 400 or 800 mg of genistein/kg of diet. The experimental
      period lasted 90 d with a 17L:7D photo schedule. As antioxidant indices, yolk MDA
      and vitamin (A and E) concentrations were measured by HPLC. Dietary genistein
      supplementation (800 mg/kg) increased feed intake, egg production, egg weight,
      Haugh unit, shell thickness, and shell weight and improved feed efficiency at a
      greater extent than the other levels (0 and 400 mg/kg). Egg yolk genistein
      concentration was increased (P<0.0001), whereas egg yolk MDA concentration was
      decreased (P<0.0001) at the highest level of genistein supplementation. However,
      genistein supplementation did not affect egg yolk daidzein, vitamin A, and
      vitamin E levels. There was an inverse relationship between egg yolk genistein
      and MDA concentration (y=0.02xe(genistein), R2=0.74, P<0.0001). Results of the
      present study indicate that supplementing with dietary genistein (800 mg/kg)
      improved performance, egg quality, and egg yolk genistein content and decreased
      egg yolk MDA concentration in quail.

PMID- 19762867
TI  - The effect of diets containing soybean meal, soybean protein concentrate, and
      soybean protein isolate of different oligosaccharide content on growth
      performance and gut function of young turkeys.
AB  - An experiment was conducted to investigate the effects of diets containing
      soybean meal (SBM), soybean protein concentrate (SPC), and soybean protein
      isolate (SPI) on growth performance and gut function of the young turkey. A total
      of 812 one-day-old male turkey poults were randomly assigned to 4 dietary
      treatments, with 7 pens per treatment and 29 birds per pen. The 4 experimental
      diets contained SBM, SBM-SPC, SPC, and SPI and were fed throughout the two 4-wk
      experimental periods. In each period, the diets were isonitrogenous and
      isocaloric and contained similar amounts of total and water-soluble nonstarch
      polysaccharides. The content of oligosaccharides differed among the diets and
      averaged 2.4, 1.9, 0.9, and 0.1% for SBM, SBM-SPC, SPC, and SPI, respectively.
      When compared with SBM, birds consuming the SBM-SPC and SPC diets had higher
      (P<0.05) final BW (4.32 vs. 4.45 and 4.46 kg, respectively). Incorporation of SPI
      as a substitute for SBM resulted in improved (P<0.05) feed utilization (from 1.76
      to 1.67) but did not affect the final BW. Significant changes in cecal
      concentrations of short-chain fatty acids were observed and averaged 130, 103,
      and 89 micromol/g of digesta for the SBM, SBM-SPC, and SPC diets, respectively.
      This coincided with the proportional decrease in dietary oligosaccharide content
      (from 2.4 to 0.9%) and was further substantiated by a significant decrease in
      ileum weights. Feeding the SPI diet resulted in the lowest ileal and cecal tissue
      weights as well as the lowest cecal short-chain fatty acids concentration. There
      was no effect of diet on digesta pH, viscosity, and mucosal sucrase and maltase
      activities. Bacterial beta-glucuronidase activity was decreased (P=0.08) in the
      cecum (from 0.98 to 0.60 U/g) with decreased dietary oligosaccharide content. In
      conclusion, partial or almost complete substitution of SBM with SPC suppressed
      the fermentation processes in the ceca but enhanced the growth rate. Substitution
      of SBM with SPI significantly improved feed utilization but decreased BW of 4-wk
      old turkeys with no effect on growth rate of older 8-wk-old birds.

PMID- 19762868
TI  - Effect of Saccharomyces cerevisiae fermentation product on immune functions of
      broilers challenged with Eimeria tenella.
AB  - Three hundred sixty 1-d-old male Arbor Acres broilers were randomly allotted to 6
      groups with a 2x3 factorial arrangement of treatments. Three supplemental levels
      (0, 0.25, and 0.50%) of Saccharomyces cerevisiae fermentation product (XP) were
      fed to control and Eimeria tenella-infected broilers. Growth performance and
      immune response criteria were measured after coccidian infection. Broiler ADG was
      lowered (P<0.01) by coccidian infection and improved by XP supplementation
      (P=0.04). Supplementation of XP increased CD3+, CD4+, and CD8+ T-lymphocyte
      counts (P<0.05) and the ratio CD4+:CD8+ in blood (P=0.06) and spleen (P=0.04) as
      well as ileum intraepithelial lymphocyte count, cecal tonsil secretory IgA
      counts, serum lysozyme content (P<0.01), and albumin:globulin ratio (P=0.02).
      These results suggest that dietary XP supplementation could improve immune
      function and growth performance in coccidia-infected broilers.

PMID- 19762869
TI  - Pediocin A improves growth performance of broilers challenged with Clostridium
      perfringens.
AB  - The aim of this study was to investigate the efficacy of the anticlostridial
      pediocin A from Pediococcus pentosaceus FBB61 to contain negative effects
      associated to Clostridium proliferation in broilers, through 2 subsequent
      investigations. In the first study, 36 Ross 508 broilers were divided into 3
      groups and fed for 21 d as follows: the control diet (CTR), the control diet
      supplemented with supernatant filtrate of a culture of P. pentosaceus FBB61-2
      (Bac-, isogenic mutant nonproducing pediocin A), and the control diet
      supplemented with supernatant filtrate of a culture of P. pentosaceus FBB61
      (Bac+) containing pediocin A. Birds were challenged with 10(6) cells of
      Clostridium perfringens. In the second study, 216 Ross 508 broilers were
      allocated in 18 pens and divided into 3 groups fed the same diet for 42 d: a
      control group (CTR), a group challenged with 10(8) cells of C. perfringens (CP),
      and a group challenged with 10(8) cells of C. perfringens and receiving the
      control diet supplemented with P. pentosaceus FBB61 and pediocin A (PA). Broiler
      BW, ADG, ADFI, and feed conversion rate were measured throughout the studies. At
      the end of both experiments, an appropriate number of birds was killed and
      analyzed for necrotic enteritis lesions and microbiological examinations. In the
      first study, on d 9, ADG and BW were 20% higher for Bac+ compared with CTR and
      Bac-; on d 14, ADG was higher for Bac+ (+23%, P<0.05), whereas BW was higher for
      Bac+ and Bac- compared with CTR (+23 and +14%, respectively; P<0.05). In the
      second study, on d 14, ADG and BW were higher for PA compared with CTR and CP
      (+15% on average; P<0.05), whereas between 15 and 42 d, there was only a tendency
      toward a higher ADG for PA when compared with the CP group (+4%, P=0.08). Diet
      supplementation with pediocin A improved broiler growth performance during the
      challenge with C. perfringens and tended to restore the ADG depletion during the
      42-d period.

PMID- 19762870
TI  - Effects of ginger root (Zingiber officinale) processed to different particle
      sizes on growth performance, antioxidant status, and serum metabolites of broiler
      chickens.
AB  - A study using 144 one-day-old Arbor Acres broilers was conducted to assess the
      effects of dried ginger root (Zingiber officinale) that was processed to particle
      sizes of 300, 149, 74, 37, and 8.4 microm on growth performance, antioxidant
      status, and serum metabolites of broiler chickens. The birds were housed in 24
      wire cages in an environmentally controlled room. Dietary treatments were no
      supplementation (control) and supplementation with ginger root processed to 5
      particle sizes at the level of 5 g/kg of diet. Average daily gain, ADFI, and feed
      conversion rate of chicks of each cage were measured weekly. Blood samples from 8
      broilers per treatment were obtained at d 21 and 42 of the experiment to
      determine antioxidant enzymatic activities and metabolites in the serum, and the
      birds were subsequently killed to determine carcass yield and abdominal fat
      content. All broilers had similar ADFI or feed conversion rate over the entire
      experimental period. However, broilers supplemented with ginger powder tended to
      have higher ADG and had greater (P=0.014) carcass yield compared with that of the
      control. Supplementation of ginger increased (P<0.001) activities of total
      superoxide dismutase and glutathione peroxidase but reduced (P<0.01)
      concentrations of malondialdehyde and cholesterol in serum of broilers at 21 and
      42 d of age. Concentration of total protein in serum of ginger-supplemented
      broilers tended (P=0.092) to be higher at 21 d and was higher (P=0.002) at 42 d
      of age compared with that of control broilers. Reducing particle size of ginger
      powder linearly reduced (P<0.05) cholesterol (d 21) and linearly increased
      (P<0.05) glutathione peroxidase (d 21), total superoxide dismutase (d 42), and
      total protein (d 21 and 42). Supplementation of ginger at the level of 5 g/kg
      improved antioxidant status of broilers and the efficacy was enhanced as the
      particle size was reduced from 300 to 37 microm.

PMID- 19762871
TI  - Melamine residues in tissues of broilers fed diets containing graded levels of
      melamine.
AB  - An experiment was conducted to determine melamine residual levels in the tissues
      of broiler chickens fed diets containing graded levels of melamine. Ten
      experimental diets were developed to contain 0, 2, 5, 10, 20, 50, 100, 200, 500,
      and 1,000 mg of melamine/kg of diet. Each diet was offered in 4 replicate cages
      (12 birds per cage) from d 1 to 42, followed by a 7-d feeding of a withdrawal
      diet that contained no melamine. On d 28, 42, and 49, one bird per replicate was
      killed and tissue samples from the breast meat, liver, and kidney were collected
      for the determination of residual melamine levels. Throughout the 42-d feeding
      period, feeding diets containing graded levels of melamine had no effect (P>0.05)
      on the weight gain, feed intake, feed conversion ratio, and mortality of broiler
      chickens. Residue levels of melamine in broiler tissues at d 28 and 42 were below
      the detection limit when the diets contained<or=50 mg/kg of melamine. At d 28,
      tissue melamine levels increased (P<0.05) with the increasing levels of melamine
      in birds fed diets containing higher than 100 mg/kg. At d 42, a similar trend was
      observed in the kidney, but melamine was detected in breast meat and liver only
      in birds fed diets containing 500 and 1,000 mg of melamine/kg of diet. Melamine
      distribution varied (P<0.05) in different tissues, with the highest concentration
      in the kidney. A withdrawal period of 7 d was found to clear the tissues of
      melamine.

PMID- 19762872
TI  - Effects of feeding different forms of zinc and copper on the performance and
      tissue mineral content of chicks.
AB  - A study was conducted to investigate the effects of feeding inorganic or organic
      Zn and Cu on the performance and tissue mineral content of chicks. A corn-soybean
      meal diet without Cu and Zn supplementation, containing 31 mg of Zn/kg of diet
      and 6.6 mg of Cu/kg of diet, was used as a basal diet. Organic Zn (a chelated Zn
      proteinate) and organic Cu (a chelated Cu proteinate) were used as organic
      sources for comparison with inorganic reagent-grade sulfates. Supplements
      provided 20 mg/kg of Zn and 8 mg/kg of Cu. A 3x3 factorial arrangement of
      treatments consisting of feeding the basal diet with 3 supplements (none,
      sulfate, or organic) of Cu and of Zn was used. Ten groups of 6 one-day-old male
      broilers were assigned to each of 9 dietary treatments. Tap water and feed were
      supplied on an ad libitum basis during the 3-wk trial. The Zn and Cu content in
      the mucosa of the duodenum of the chick was determined. Dietary supplementation
      of Zn increased (P<0.01) weight gain, feed intake, and G:F of chicks. The G:F for
      chicks fed both inorganic sources of Zn and Cu was lower (P<0.01) than that for
      chicks fed only the inorganic source of Zn. Dietary inclusion of Zn increased
      (P<0.01) tibia and plasma Zn content. The tibia Zn content for chicks fed organic
      Zn was higher (P<0.01) than that for chicks fed inorganic Zn. Liver Cu content
      was decreased (P<0.05) by dietary inclusion of Zn. The Zn and Cu contents in the
      mucosa of chicks fed the organic source were higher (P<0.01) than those of chicks
      fed the control diet. The feed conversion data suggest that the antagonism
      between Zn and Cu occurred when the inorganic forms, but not organic forms, of
      these 2 minerals were included in a chick diet.

PMID- 19762873
TI  - Role of dietary zinc in heat-stressed poultry: a review.
AB  - High ambient temperatures compromise performance and productivity through
      reducing feed intake and decreasing nutrient utilization, growth rate, egg
      production, egg quality, and feed efficiency, which lead to economic losses in
      poultry. Environmental stress also leads to oxidative stress associated with a
      reduced antioxidant status in the bird in vivo, as reflected by increased
      oxidative damage and lowered plasma concentrations of antioxidant vitamins (e.g.,
      vitamins E, A, and C) and minerals (e.g., Zn). Zinc has an important role in
      numerous biological processes in avian and mammalian species. For instance, Zn is
      an essential component of many enzymes, and it has both structural and catalytic
      functions in metalloenzymes. Furthermore, dietary Zn is required for normal
      immune function as well as proper skeletal development and maintenance. One of
      the most important functions of Zn is related to its antioxidant role and its
      participation in the antioxidant defense system. This work compiles past and
      present information about the role of Zn in heat-stressed poultry health.

PMID- 19762874
TI  - Evaluation of glycerol removal techniques, cryoprotectants, and insemination
      methods for cryopreserving rooster sperm with implications of regeneration of
      breed or line or both.
AB  - A series of experiments was designed to evaluate the quality of cryopreserved
      rooster sperm and its fertility so that programs needing to bank germplasm and
      recreate animals can do so utilizing a minimal amount of cryopreserved semen. In
      experiment 1, rooster semen from the National Animal Germplasm Program genebank
      was thawed and glycerol was removed using a discontinuous Accudenz column or by
      stepwise dilution. The postthaw sperm motilities, plasma membrane integrity, and
      concentration were determined before and after deglycerolization. Line
      differences in postthaw sperm concentration and progressive motility were
      observed before deglycerolization (P<0.05). After glycerol removal, the sperm
      that was centrifuged through Accudenz had greater total motility (37 vs. 33%
      sperm; P<0.05), but use of the stepwise dilution method recovered more sperm per
      milliliter (320.4x10(6)) compared with the Accudenz method (239.2x10(6) sperm;
      P<0.05; range across 6 lines of 165.7 to 581.0x10(6) sperm/mL). In experiment 2,
      rooster semen was cryopreserved using Lake's diluent containing either dimethyl
      acetamide (DMA) or glycerol as the cryoprotectants. Postthaw analysis revealed
      that the samples cryopreserved with glycerol survived freezing better, determined
      by total motility (47.8 and 15.1% glycerol and DMA samples, respectively; P<0.05)
      and annexin V analyses (1.6 and 11.3% membrane-damaged sperm for glycerol and DMA
      samples, respectively; P<0.05). Differences in sperm motilities (total and
      progressive motility) and velocities (path velocity, straight-line velocity,
      curvilinear velocity) were observed between the 2 cryoprotectant treatments once
      the glycerol had been removed from those samples cryopreserved with glycerol, of
      which the glycerol samples had significantly more motile sperm and higher
      velocities (P<0.05). The fertility of the samples frozen using the 2
      cryoprotectants was tested using a single insemination (intravaginal or
      intramagnal) of 200x10(6) sperm and the fertility (number of live embryos) was
      evaluated over 18 d. Overall, the intravaginal inseminations had lower fertility
      than the intramagnal inseminations (P<0.05). In the intravaginal inseminations,
      the sperm cryopreserved using DMA resulted in lower fertility, but there were no
      differences in fertility in the intramagnal inseminations due to cryoprotectant
      (P>0.05). These results indicate that reasonable postthaw sperm quality and
      fertility can be derived using cryopreserved rooster semen. By utilizing this
      information, estimations can be made for storing sufficient material for line or
      breed, or both, recreation programs.

PMID- 19762875
TI  - Inseminating fresh or cryopreserved semen for maximum efficiency: implications
      for gene banks and industry.
AB  - Developing gene bank germplasm collections for animal genetic resources requires
      establishing germplasm collection goals, that consider capturing the genetic
      diversity of the population in question and the amount of germplasm required for
      its reconstitution or other purposes, or both. Computing collection goals for
      chickens is complicated, compared with mammalian species, due to the multiple
      chances a single insemination of semen has to fertilize an egg. To address this
      issue, fertility data were used in conjunction with econometric procedures for
      determining production efficiency and diminishing returns. Experimental
      treatments consisted of inseminating fresh semen intravaginally (FIV), frozen
      thawed semen inseminated intramagnally (FTIM), and frozen-thawed semen
      inseminated intravaginally (FTIV). Analysis revealed that the maximum efficiency
      for a single insemination was at postinsemination d 6, 8, and 3 for FIV, FTIM,
      and FTIV, respectively. But, additional benefit from a single insemination can be
      garnered by continuing to collect and incubate eggs to d 11, 17, and 11 for FIV,
      FTIM, and FTIV, respectively. By extending the insemination interval, the number
      of fertile eggs can be increased by 62 (FIV), 62 (FTIM), and 48% (FTIV). The
      ramifications of these results are profound when placed in the context of
      germplasm collection for gene banks. By using the FTIM treatment, the number of
      germplasm samples needed to secure a chicken breed, at the 150% level, can be
      reduced from the FAO projection of 2,454 to 386 straws (0.5 mL). Such a change
      represents a substantial reduction in collection, processing, and storage costs
      for gene banks. For industry, the results suggest that extending the time
      interval between inseminations will yield more fertile eggs and create
      opportunities to increase the number of hens mated to a rooster.

PMID- 19762876
TI  - Calcitonin directly increases adrenocorticotropic hormone-stimulated
      corticosterone production in the hen adrenal gland.
AB  - The present study was performed to elucidate whether the receptor for calcitonin
      (CT) exists in the adrenocortical cells of hens and to determine the effect of CT
      on adrenocorticotropic hormone (ACTH)-stimulated corticosterone production in its
      cell. The binding site of CT in the membrane fraction of the adrenal gland in
      hens was determined using a [125I]CT binding assay system. The binding properties
      in the adrenal gland satisfied the criteria of a receptor-ligand interaction in
      terms of specificity, reversibility, and saturation. When the cortical cells were
      incubated in vitro with chicken ACTH in the presence of CT, greater
      corticosterone production was observed. The result suggested that CT acts
      directly on the adrenocortical cells via its receptor binding and increases
      responsiveness of ACTH on corticosterone production in the laying hen.

PMID- 19762877
TI  - Properties of estrogen binding components in the plasma membrane of
      neurohypophysis in hens and changes in its binding before and after oviposition.
AB  - The present study was performed to elucidate whether the estrogen binding
      component regarded as a receptor exists in the plasma membrane fraction of
      neurohypophysis in hens and whether the binding of receptor changes with relation
      to oviposition. The specific binding for estradiol-17beta (E2) in the
      neurohypophysis of hens was demonstrated by the use of radioligand binding assays
      on the plasma membrane fraction of the tissue. The binding to [3H]E2 had a
      binding specificity to E2 and diethylstilbestrol, reversibility, and saturation.
      Scatchard analysis revealed that the binding sites are of a single class. The
      equilibrium dissociation constant obtained by Scatchard analysis and kinetic
      analysis suggested a high affinity, and the maximum binding capacity obtained by
      Scatchard analysis suggested a limited capacity. These properties are
      characteristics of a receptor, which suggests that an estrogen receptor exists in
      the plasma membrane of hen neurohypophysis. The equilibrium dissociation constant
      value of estrogen receptor of the neurohypophysis was not significantly different
      between laying hens and nonlaying hens, but the maximum binding capacity value
      was statistically smaller (the binding affinity is higher) in laying hens than in
      nonlaying hens. The specific binding of estrogen receptor showed a decrease at 1
      h after an injection of diethylstilbestrol in nonlaying hens. The specific
      binding also decreased 3 h before oviposition in laying hens and maintained low
      value until just after oviposition. The present study suggests that estrogen may
      act directly on the neurohypophysis during 3 h before oviposition in hens.

PMID- 19762878
TI  - Variation of meat quality traits among five genotypes of chicken.
AB  - The main objective of this study was to examine the diversity of meat quality
      traits among 5 chicken genotypes. The genotypes included 2 Chinese native breeds
      (Wenchang,WCH, and Xianju), 1 commercial broiler line (Avian, AV), 1 commercial
      layer line (Hy-Line Brown, HLB), and 1 Chinese commercial broiler line
      (Lingnanhuang, LNH) synthesized by exotic and native breeds, which were
      slaughtered at their market ages: 16, 7, 16, and 8 wk, respectively. The effects
      of genotype, muscle type, and sex on meat quality traits were examined. Birds
      from slow-growing genotypes (WCH, Xianju, and HLB) exhibited higher shear value,
      inosine-5'-monophosphate concentration, lower cook loss, and more fat than those
      from fast-growing genotypes (AV and LNH). Chickens from WCH possessed the lowest
      expressible moisture, cook loss, and the highest lipid (%) among the 3 slow
      growing genotypes. The HLB birds were intermediate in expressible moisture and
      cook loss and lowest in lipid among all genotypes. The LNH cross birds were
      similar to AV broilers in most meat quality parameters, although they had a lower
      shear force value and higher fat content than AV broilers. Breast muscle had
      higher expressible moisture, shear force, protein (%), inosine-5'-monophosphate
      content, lower cook loss, and lipid (%) than leg muscle. Muscles from male
      chickens had higher expressible moisture than those from the females. Variability
      of meat quality characteristics is mainly related to genotype and muscle type
      differences.

PMID- 19762879
TI  - Effect of a free-range raising system on growth performance, carcass yield, and
      meat quality of slow-growing chicken.
AB  - Experiments were conducted to evaluate the effect of free-range raising systems
      on growth performance, carcass yield, and meat quality of slow-growing chickens.
      Slow-growing female chickens, Gushi chickens, were selected as the experimental
      birds. Two hundred 1-d-old female chicks were raised in a pen for 35 d. On d 36,
      ninety healthy birds, with similar BW (353.7+/-32.1g), were selected and randomly
      assigned to 2 treatments (indoor treatment and free-range treatment, P>0.05).
      Each treatment was represented by 3 groups containing 15 birds (45 birds per
      treatment). During the indoor treatment, the chickens were raised in floor pens
      in a conventional poultry research house (7 birds/m2). In the free-range
      treatment, the chickens were housed in a similar indoor house (7 birds/m2); in
      addition, they also had a free-range grass paddock (1 bird/m2). All birds were
      provided with the same starter and finisher diets and were raised for 112 d.
      Results showed that the BW and weight gain of the chickens in the free-range
      treatment were much lower than that of the chickens in the indoor floor
      treatments (P<0.05). There was no effect of the free-range raising system on
      eviscerated carcass, breast, thigh, and wing yield (P>0.05). However, the
      abdominal fat yield and tibia strength (P<0.05) significantly declined. The
      nutrient composition (water, protein, and fat), water-holding capacity, shear
      force, and pH of the muscle were largely unaffected (P>0.05) by the free-range
      raising system. The data indicated that the free-range raising system could
      significantly reduce growth performance, abdominal fat, and tibia strength, but
      with no effect on carcass traits and meat quality in slow-growing chickens.

PMID- 19762880
TI  - Effect of different concentrations of calcium chloride and potassium chloride on
      egg white proteins during isoelectric precipitation of ovomucin.
AB  - The effect of various concentrations of CaCl2 and KCl on egg white proteins
      during isoelectric precipitation of ovomucin was investigated in this study. At
      low concentrations of CaCl2 (<50 mM), lysozyme was the major contaminant in the
      precipitated ovomucin, whereas ovalbumin was the predominant one at high
      concentrations (>or=100 mM). At 50 mM CaCl2 concentration, the concentrations of
      both lysozyme and ovalbumin were moderate. Ovomucin with a purity of 97.3% was
      prepared using a 2-step method: egg white was first precipitated in the presence
      of 50 mM CaCl2 followed by a second 500 mM CaCl2 extraction. The concentrations
      of other proteins in the precipitate were 1.3% of ovalbumin, 1.1% of lysozyme,
      and 0.4% of ovomucoid. Unlike CaCl2-treated samples, ovotransferrin was found to
      be the second major contaminant in all KCl-treated precipitates. Compared with
      the control, adding KCl at the lowest concentration of 2.5 mM increased
      significantly the content of ovalbumin (from 7.6 to 68.0%) and reduced
      significantly the content of lysozyme (from 25.5 to 6.4%) in the precipitates;
      however, increasing the concentrations of KCl up to 500 mM did not affect the
      content of ovalbumin, but the content of lysozyme showed a general reduction
      trend. Although KCl was used widely in literature as the last step of ovomucin
      washing, our results show that KCl is not an efficient salt in purifying
      ovomucin.

PMID- 19762881
TI  - Control of Listeria monocytogenes in turkey deli loaves using organic acids as
      formulation ingredients.
AB  - The growth of Listeria monocytogenes in further-processed meat products has
      become a major concern and an important food safety issue. The meat and poultry
      industries have incorporated interventions such as organic acids in marinades to
      inhibit the growth of L. monocytogenes. In this study, organic acids were
      utilized in the raw product and as a postcook dip to determine their inhibitory
      effect on the growth of L. monocytogenes in turkey deli loaves. The turkey deli
      loaves were processed, cooked, cooled, inoculated with streptomycin-resistant L.
      monocytogenes, and then dipped. Treatments were potassium lactate (PL) in the raw
      product with sodium lactate (SL), sodium diacetate (SD) dip, PL with SL/PL/SD
      dip, SL with SL/SD dip, and SL with SL/PL/SD dip. There was also a positive
      (inoculated) and negative (noninoculated) control, which was dipped in distilled
      water. Days 0, 7, 14, 21, 28, 42, and 56 were sampled for L. monocytogenes. There
      were no differences (P>0.05) among the organic acid treatments in the turkey deli
      loaves at any time points; therefore, all of the treatments increased the lag
      phase of L. monocytogenes, extending the shelf-life of the product. However,
      there was a difference between the treatments and the positive control at d 7,
      14, 21, 28, 42, and 56. The growth of L. monocytogenes increased immediately in
      the positive control, whereas the negative control appeared to have no growth.
      These organic acids can provide meat processors with a useful method for
      extending the lag phase of L. monocytogenes in ready-to-eat meat and poultry
      products.

PMID- 19762882
TI  - 'There are too many of us to fix.' Patients' views of acceptable waiting times
      for hip and knee replacement.
AB  - OBJECTIVES: To assess patients' views of maximum acceptable waiting times (MAWT)
      for hip and knee replacement, associated factors and the accuracy of self
      reported waiting times. METHODS: We mailed 1000 questionnaires each to two random
      samples of patients either waiting for or who had received an arthroplasty within
      the preceding 3-12 months. We used linear regression to assess the determinants
      of patient MAWT, and content analysis to assess reasons for MAWT and ideal
      waiting time. RESULTS: Of the 1330 responses, 1127 had MAWT data. The sample was
      57% women; mean age was 70 +/- 11 years. Median self-reported and actual waiting
      time was eight months (Spearman correlation = 0.70). Median MAWT was four months
      and ideal waiting time was two months. The most frequent reasons for MAWT were
      pain, quality of life and needing time to prepare for surgery. A longer MAWT was
      associated with younger age, group (waiting), a longer self-reported waiting
      time, better EQ-5D index, an acceptable waiting time, a perception of fairness
      and a view that others worse off on the list should go ahead. CONCLUSIONS:
      Patients' views of acceptable waiting times are important for a fair process of
      establishing waiting time benchmarks for joint replacement.

PMID- 19762883
TI  - Thematic analysis and its reconceptualization as 'saliency analysis'.
AB  - Thematic analysis is characteristic of most qualitative research. Themes are
      groups of codes that recur through being similar or connected to each other in a
      patterned way. Thematic analysis ignores codes that do not recur yet may
      nonetheless be important. This paper proposes the concept of 'saliency analysis'
      as an enhancement of thematic analysis. Saliency analysis assesses the degree to
      which each code recurs, is highly important or both. Codes of high importance are
      ones that advance understanding or are useful in addressing real world problems,
      or both. Thus saliency analysis can expose what is non-recurrent but potentially
      important to the aims of a study.

PMID- 19762884
TI  - DWA (down with abbreviations!).

PMID- 19762885
TI  - Reversible cerebral vasoconstriction syndrome.
AB  - Reversible cerebral vasoconstriction syndrome is characterised by severe
      headaches with or without seizures and focal neurological deficits, and
      constriction of cerebral arteries which resolves spontaneously in 1-3 months. It
      affects females slightly more than males, and mean age of onset is around 45
      years. Approximately 60% of cases are secondary, mainly postpartum and after
      exposure to vasoactive substances. The major complications are localised cortical
      subarachnoid haemorrhage (22%) and parenchymal ischaemic or haemorrhagic strokes
      (7%) which may leave permanent sequelae. Diagnosis requires the demonstration of
      the "string of beads" appearance of cerebral arteries on angiography, with
      complete or almost complete resolution on repeat angiography 12 weeks after
      onset. Nimodipine seems to reduce thunderclap headaches within 48 h but has no
      definite effect on the haemorrhagic and ischaemic complications.

PMID- 19762886
TI  - Treating women with juvenile myoclonic epilepsy.
AB  - Epilepsy has special implications for women, especially during their childbearing
      years, and particularly when pregnancy is contemplated. Being aware of the
      relevant issues is therefore essential. For anyone with juvenile myoclonic
      epilepsy and other idiopathic generalised epilepsies, valproate is generally
      regarded as the gold standard treatment against which other antiepileptic drugs
      are compared. However, information from pregnancy registers consistently show
      valproate to be associated with the highest risk for major congenital
      malformations, and studies exploring cognitive and behavioural development of
      offspring also show that valproate has an adverse impact. This creates a
      significant headache when trying to choose the "right" drug for most women with a
      generalised epilepsy syndrome.

PMID- 19762887
TI  - NICE and neurology.
AB  - The National Institute for Health and Clinical Excellence (NICE) is 10 years old
      and has now issued a number of technology appraisals for new treatments for
      neurological disorders. Those for multiple sclerosis and dementia have been
      controversial and have attracted particular media attention, to say nothing of
      strong feelings within British neurology. Some of its other activities, which
      include both appraisals of interventions and clinical guidelines, have attracted
      less notice but form an important part of its remit. There is no doubt that NICE
      has had an impact on neurological care in the UK which for the most part has been
      beneficial. It has a vital role in managing the relationship between the NHS and
      pharma, and helps ensure equity in access to new and potentially expensive
      treatments.

PMID- 19762888
TI  - An error of self-diagnosis--but what was the real diagnosis?
AB  - The availability of information on the internet encourages people to explore
      their own diagnosis. Although more knowledge is usually a good thing, self
      diagnosis in this way may not always be correct, and it can even adversely
      influence the medical diagnosis, as in this patient, where the underlying
      disorder is still uncertain. The patient illustrates the confusion and difficulty
      in categorising an usual clinical syndrome.

PMID- 19762889
TI  - Miller Fisher syndrome.

PMID- 19762890
TI  - From Perugia to Oxford in 1984.

PMID- 19762891
TI  - Thunderclap headache.

PMID- 19762892
TI  - Neurological letter from Austria.

PMID- 19762893
TI  - The current status of "Fahr's disease" nosology.

PMID- 19762894
TI  - Motor neuron disease: the bare essentials.

PMID- 19762895
TI  - Lacrimation, conjunctival injection, nasal symptoms... cluster headache, migraine
      and cranial autonomic symptoms in primary headache disorders -- what's new?

PMID- 19762896
TI  - Size and flow matter in the posterior circulation.

PMID- 19762897
TI  - Primary focal dystonia -- a disease of brain and mind: motor and psychiatric
      manifestations have a common neurobiological basis.

PMID- 19762898
TI  - Evaluation and treatment of inflammatory myopathies.
AB  - The major types of idiopathic inflammatory myopathy include dermatomyositis (DM),
      polymyositis (PM), inclusion body myositis (IBM) and immune mediated necrotising
      myopathy (NM). These myositides appear clinically, histologically and
      pathogenically distinct. DM, PM and immune mediated NM are responsive to
      immunosuppressive therapy, in contrast with IBM which is generally refractory to
      therapy. Greater understanding of the pathogenic bases of these disorders should
      hopefully lead to better treatment. We need well designed, prospective, double
      blind, placebo controlled trials in order to determine the best therapeutic
      options for these different disorders.

PMID- 19762899
TI  - The oldest old Creutzfeldt-Jakob disease case.
AB  - Sporadic Creutzfeldt-Jakob Disease (sCJD) is a rapidly progressive
      neurodegenerative disorder usually affecting people between 60 and 70 years old,
      with only anecdotal cases presenting at 90 years or older. The clinical phenotype
      of sCJD is highly variable. Diagnosis of sCJD should be considered in the
      differential diagnosis of rapidly evolving ataxic or dementing syndromes with or
      without epileptic seizures, regardless of the patient age. While the recognition
      of atypical phenotypes in subject 90 years or older can provide additional
      diagnostic challenge, it must be underlined that neuropathology is still the
      "gold standard" for sCJD diagnosis.

PMID- 19762900
TI  - Neurological picture. Isolated toe paralysis caused by a small cortical
      infarction.

PMID- 19762901
TI  - Emotion recognition in progressive supranuclear palsy.
AB  - Progressive supranuclear palsy (PSP) is an atypical parkinsonian syndrome
      characterised by akinesis, rigidity, falls, supranuclear gaze palsy and
      cognitive, particularly executive, dysfunction. This study examined the extent to
      which emotion recognition is affected by PSP. Although deficits in the
      recognition of emotion have been reported in several diseases which share
      clinicopathological characteristics with PSP, it has never been studied
      systematically in PSP. Twenty-four patients with probable or definite PSP and
      matched healthy controls were studied using tests of facial identity and facial
      emotion recognition. Patients were not impaired in recognising famous faces, but
      they showed significant deficits in the recognition of emotions, particularly
      negative emotions. Moreover, emotion recognition was strongly correlated with the
      severity of other cognitive deficits in PSP, but not disease duration. Deficits
      in emotion recognition form an integral part of the cognitive spectrum of the
      disease. The findings point to the pathological involvement of key regions
      necessary for the processing of emotions and to a subtype of PSP with cognitive
      and emotion recognition impairments. The acknowledgement of deficits in emotion
      recognition is important for management of both patients and their carers.

PMID- 19762902
TI  - Prevalence of fatigue and depression in ALS patients and change over time.
AB  - BACKGROUND: Amyotrophic lateral sclerosis (ALS) patients report both fatigue and
      depression. It is not clear how frequently each occurs, to what extent they occur
      together, how each relates to ALS disease status, or their stability over time.
      OBJECTIVE: To assess frequency and persistence of fatigue and depression, and
      relationship to ALS disease status, for patients attending an ALS
      interdisciplinary centre for routine 3-month visits. METHOD: Measures included
      the Fatigue Severity Scale, Patient Health Questionnaire-9. ALS Functional Rating
      Scale -- Revised and forced vital capacity, rate of disease progression, and
      bulbar/nonbulbar disease onset. RESULTS: 223 patients completed the ratings once;
      of these, 113 completed them twice, and 65 on three visits. At baseline, 44%
      (99/223) had clinically significant fatigue, including 34 patients who also had a
      depressive disorder; 7% (16/223) had major or minor depression only, and 48%
      (108/223) had neither condition. Fatigue was associated with greater ALS
      severity, but depression was not. Among the 113 patients seen 3 months later, 75%
      (33/44) who were fatigued at Time 1 remained fatigued, while 48% (10/21) remained
      depressed. New-onset fatigue was reported by 22% (25/113), and new-onset
      depression by 6% (7/113). For the 65 patients seen a third time, rates remained
      nearly the same. CONCLUSION: Fatigue was more prevalent and persistent than
      depression, although 15% (34/223) of patients had both conditions. Fatigue but
      not depression was associated with ALS severity. The two conditions appear to be
      independent, although sometimes co-occurring, and both warrant consideration in
      evaluating patient functioning and treatment.

PMID- 19762903
TI  - Neurological picture. Huge primary intracranial hydatid cysts.

PMID- 19762904
TI  - Craniopharyngiomas in the posterior fossa: a rare subgroup, diagnosis, management
      and outcomes.
AB  - OBJECTIVE: Craniopharyngiomas with predominant pars in the posterior fossa are
      very rare and extremely overlooked. The clinical features, diagnosis and
      management are different from their sellar/suprasellar counterparts. The purpose
      of this study was to explore the differing characteristics of posterior fossa
      craniopharyngiomas. METHODS: Seven patients with pathologically proven
      craniopharyngiomas located in the posterior fossa were retrospectively
      investigated. The clinical data and radiographic findings were presented and
      analysed. RESULTS: The primary presentations included headache, diplopia, ataxia
      and hearing loss. All tumours were located in the retrochiasmatic area, and five
      of seven displayed a retroinfundibulum growth pattern. The predominant components
      of the tumours were located in the unilateral cerebellopontine angle (CPA) in six
      cases, and the bilateral CPA in one case. Total tumour resection was accomplished
      in five patients. There were transient cranial nerve deficits in three patients,
      and CSF leakage in one patient. Six patients fully recovered to normal
      conditions, but one patient had tumour regrowth and had to undergo a secondary
      resection. CONCLUSIONS: Posterior fossa craniopharyngiomas are rare and may be
      considered an independent subgroup of classifications. Tumours arising from the
      sellar region and extending to the posterior fossa present with their own unusual
      set of characteristics. These tumours can be radically and safely removed with a
      combined supra- and intratentorial approach.

PMID- 19762905
TI  - Neurological picture. Bilateral internal carotid artery dissection due to
      elongated styloid processes and shaking dancing.

PMID- 19762906
TI  - Thrombolysis targeting MRI defined tissue at risk in minor stroke.
AB  - BACKGROUND: Treatment with intravenous tissue plasminogen activator (IV-tPA) is
      usually not recommended in patients with minor stroke. Clinical and imaging
      outcome were studied after IV-tPA treatment based on MRI criteria in patients
      with minor stroke. METHODS: Data were analysed retrospectively of acute ischaemic
      stroke patients with minor stroke (National Institutes of Health Stroke Scale
      (NIHSS) score <4). All patients were studied by stroke MRI including perfusion
      and diffusion weighted imaging (PWI and DWI) and treated with IV-tPA for < or =6
      h. Final infarct volume was delineated on follow-up MRI. Clinical outcome was
      assessed after 90 days using the modified Rankin Scale (mRS). RESULTS: Six
      patients with a median NIHSS on admission of 2 (range 0-3) were treated with IV
      tPA based on MRI criteria. In all patients, occlusion of the middle cerebral
      artery (MCA) was detected (MCA branch n = 2, MCA trunk n = 3, MCA trifurcation n
      = 1), and the PWI lesion (41, 25-60 ml) exceeded the DWI lesion (4, 1-23 ml).
      Final infarct volume was 9 (2-29) ml. Favourable outcome (mRS 0-1) was seen in
      5/6 patients and independent outcome (mRS = 2) in one patient. No intracerebral
      haemorrhages occurred. CONCLUSION: Treatment with IV-tPA based on MRI criteria
      was safe and appeared to be effective in this small series of patients with minor
      stroke.

PMID- 19762907
TI  - Primary angiitis of the central nervous system: response to mycophenolate
      mofetil.
AB  - Primary angiitis of the central nervous system (PACNS) is a rare inflammatory
      disease restricted to the CNS of unknown cause. Clinical presentation and
      evolution are highly variable with potentially fluctuating signs and symptoms.
      Brain imaging often shows supratentorial ischaemic lesions. Definite diagnosis is
      established by brain biopsy. Treatment usually combines glucocorticosteroids and
      cyclophosphamide. A case of PACNS is reported here, which was proved by a brain
      biopsy and characterised by unusually prominent involvement of the posterior
      cerebral fossa. Successful treatment with mycophenolate mofetil in combination
      with steroids is described.

PMID- 19762908
TI  - Relapsing neuromyelitis optica: long term history and clinical predictors of
      death.
AB  - BACKGROUND: Relapsing neuromyelitis optica (RNMO) is an uncommon but devastating
      inflammatory disorder of the central nervous system. Long term history in a wide
      series of RNMO is required for better knowledge of the course of the disease and
      identification of patients at high risk of death. METHODS: Clinical features of
      patients with RNMO (88 women/eight men) obtained from the geographic Caribbean
      database (Cuba and French West Indies) were used to determine the progression of
      disability and to identify clinical predictors of death. RESULTS: Median age at
      onset of RNMO was 29.5 years (range 11-74). Median duration of disease was 9.5
      years (1-40). Median relapse rate was 0.7 attack/patient/year (0.1-3). 66
      patients experienced severe visual loss in at least one eye and 46 in both eyes.
      Median time from onset to unilateral and bilateral severe visual loss was 3 and
      15 years, respectively. Median times to reach Kurtzke Disability Status Scale 3,
      6 and 8 from onset of RNMO were 1, 8 and 22 years. There were 24 deaths (25%);
      within 5 years in 63% of cases. A higher attack frequency during the first year
      of disease (p = 0.009), blindness (p = 0.04) and sphincter signs at onset (p =
      0.02) and lack of recovery of first attack (p = 0.003) were independently
      associated with a shorter time to death. CONCLUSION: RNMO is a very rapidly
      disabling disease affecting primarily young women. This study has identified
      clinical features that predict a poor outcome. These findings suggest that early
      and aggressive immunotherapy might be warranted in RNMO.

PMID- 19762909
TI  - Patterns of hearing loss after microvascular decompression for hemifacial spasm.
AB  - BACKGROUND: The purpose of this study was to analyse audiological data after
      microvascular decompression (MVD) for hemifacial spasm (HFS), and to compare the
      data with hearing before surgery. METHODS: Auditory functions were studied before
      and after surgery in 698 patients who underwent an MVD of the intracranial
      portion of the facial nerve for HFS. The results were expressed as the average of
      pure tone audiometry (PTA) and speech discrimination score (SDS). RESULTS: 668
      patients (95.7%) had no hearing loss immediately after surgery (group 1). 17
      patients (2.4%) had a postoperative decrease in PTA exceeding 15 dB and a
      decrease in SDS which was proportional to the postoperative PTA thresholds (group
      2). Eight patients (1.2%) had poor SDS that appeared to be out of proportion to
      the degree of hearing loss depicted by the postoperative PTA thresholds,
      suggesting retrocochlear or cochlear nerve pathology (group 3). Five patients
      (0.7%) had total deafness after surgery (group 4). In group 2, 12 patients
      (70.6%) returned to their preoperative hearing capacity. However, among the eight
      patients in group 3 and five in group 4, only two (25%) and none (0%) have
      returned to their preoperative hearing status, respectively. CONCLUSION: In this
      large study, permanent hearing loss occurred in 16 patients (2.2%). Patients with
      a mild hearing loss with a good SDS (cochlear type) demonstrated much better
      prognosis than those with poor SDS (retrocochlear type) or total deafness. In
      addition, total deafness after surgery had no chance of recovery to preoperative
      hearing capacity.

PMID- 19762910
TI  - Increasing incidence of elderly onset patients with myasthenia gravis in a local
      area of Japan.
AB  - OBJECTIVE: As the number of elderly patients with myasthenia gravis (MG) has
      recently increased in Europe and the USA, a retrospective survey of Japanese MG
      patients was conducted in a single neurological centre over several decades.
      METHODS: The study consisted of 112 consecutive MG patients with onset of the
      disease from 1971 to 2006 from an area of approximately 0.8 million inhabitants
      in Japan. Patients were classified into three subgroups according to age at
      onset: young onset (39 years old), middle aged onset (40-59 years old) and
      elderly onset (60 years old). The trends in incidence rate and clinical features
      were examined: disease severity, seropositivity for antiacetylcholine receptor
      antibody, occurrence of other autoimmune diseases, occurrence of thymoma and
      therapeutic response. RESULTS: The onset adjusted age specific average annual
      incidence per 100,000 of the elderly onset MG patients increased 20-fold from
      1981-1990 (0.06; 95% CI 0.00 to 0.36) to 2001-2006 (1.30; 95% CI 0.77 to 2.05).
      Clinical features of the elderly onset MG patients included low antiacetylcholine
      receptor antibody titres (mean 24.6 nmol/l), less frequent autoimmune overlaps
      (8.0%) and nearly no complete stable remission with or without thymectomy.
      CONCLUSION: The increasing incidence of elderly onset MG in Japanese patients
      similar to that reported in Caucasians has been confirmed. The clinical features
      suggest different immunological backgrounds between young onset and elderly onset
      MG patients, irrespective of the ethnic background.

PMID- 19762911
TI  - Staged gamma knife radiosurgery for large critically located benign meningiomas:
      evaluation of a series comprising 20 patients.
AB  - OBJECTIVES: This study investigated the efficacy of staged radiosurgical
      treatment for intracranial meningiomas exceeding 3 cm in diameter. METHODS:
      Between April 1992 and May 2008, staged gamma knife radiosurgery was performed in
      20 patients with large benign meningiomas. 14 patients had undergone surgery at
      least once. The patients' ages ranged between 26 and 73 years (median 60.5).
      Tumour volumes measured between 13.6 and 79.8 cm(3) (median 33.3) and treatment
      volumes between 5.4 and 42.9 cm(3) (median 19.0). Of 41 treatments, the
      prescription dose at the tumour margin was 12 Gy for 33 treatments, 10 Gy for one
      treatment, 14 Gy for four treatments, 15 Gy for one treatment and 25 Gy for a
      further two treatments (median 12 Gy to a marginal isodose of 45%). Median follow
      up was 7.5 years. RESULTS: Tumour control was achieved in 90% of our series (25%
      tumour regression, 65% stable size). Two patients (10%) experienced tumour
      progression outlying the planning target volumes treated by an additional
      radiosurgical procedure. Thereafter tumour volume decreased in one patient and
      remained stable in the second one. Clinically, nine patients (45%) improved
      within the time of follow-up and 11 (55%) remained unchanged. CONCLUSION: As a
      result of excellent tumour control at a low concomitant morbidity, staged
      radiosurgical treatment for meningiomas represents a safe treatment modality that
      can be recommended for meningiomas in critical locations either after incomplete
      surgery or as primary treatment for patients with significant comorbidity.

PMID- 19762912
TI  - Complementary mutations in seipin gene in a patient with Berardinelli-Seip
      congenital lipodystrophy and dystonia: phenotype variability suggests multiple
      roles of seipin gene.

PMID- 19762913
TI  - A variable neurodegenerative phenotype with polymerase gamma mutation.

PMID- 19762914
TI  - A biologically active sequence of the laminin alpha2 large globular 1 domain
      promotes cell adhesion through syndecan-1 by inducing phosphorylation and
      membrane localization of protein kinase Cdelta.
AB  - Laminin-2 promotes basement membrane assembly and peripheral myelinogenesis;
      however, a receptor-binding motif within laminin-2 and the downstream signaling
      pathways for motif-mediated cell adhesion have not been fully established. The
      human laminin-2 alpha2 chain cDNAs cloned from human keratinocytes and
      fibroblasts correspond to the laminin alpha2 chain variant sequence from the
      human brain. Individually expressed recombinant large globular (LG) 1 protein
      promotes cell adhesion and has heparin binding activities. Studies with synthetic
      peptides delineate the DLTIDDSYWYRI motif (Ln2-P3) within the LG1 as a major site
      for both heparin and cell binding. Cell adhesion to LG1 and Ln2-P3 is inhibited
      by treatment of heparitinase I and chondroitinase ABC. Syndecan-1 from PC12 cells
      binds to LG1 and Ln2-P3 and colocalizes with both molecules. Suppression of
      syndecan-1 with RNA interference inhibits cell adhesion to LG1 and Ln2-P3. The
      binding of syndecan-1 with LG1 and Ln2-P3 induces the recruitment of protein
      kinase Cdelta (PKCdelta) into the membrane and stimulates its tyrosine
      phosphorylation. A decrease in PKCdelta activity significantly reduces cell
      adhesion to LG1 and Ln2-P3. Taken together, these results indicate that the Ln2
      P3 motif and LG1 domain, containing the motif, within the human laminin-2 alpha2
      chain are major ligands for syndecan-1, which mediates cell adhesion through the
      PKCdelta signaling pathway.

PMID- 19762915
TI  - Oxidative stress inhibits insulin-like growth factor-I induction of chondrocyte
      proteoglycan synthesis through differential regulation of phosphatidylinositol 3
      Kinase-Akt and MEK-ERK MAPK signaling pathways.
AB  - The ability of insulin-like growth factor I (IGF-I) to stimulate cartilage matrix
      synthesis is reduced in aged and osteoarthritic cartilage. Aging and
      osteoarthritis are associated with an increase in reactive oxygen species, which
      we hypothesized would interfere with normal IGF-I signaling. We compared IGF-I
      signaling in normal and osteoarthritic human articular chondrocytes and
      investigated the effects of oxidative stress induced by tert-butylhydroperoxide
      (tBHP). In normal human chondrocytes, IGF-I initiated a strong and sustained
      phosphorylation of IRS-1 (Tyr-612) and Akt (Ser-473) and transient ERK
      phosphorylation. In contrast, in osteoarthritic chondrocytes, which possessed
      elevated basal IRS-1 (Ser-312) and ERK phosphorylation, IGF-I failed to stimulate
      IRS-1 (Tyr-612) or Akt phosphorylation. In normal human chondrocytes, tBHP
      triggered strong IRS-1 (Ser-312 and Ser-616) and ERK phosphorylation and
      inhibited IGF-I-induced IRS-1 (Tyr-612) and Akt phosphorylation. Lentivirus
      mediated overexpression of constitutively active (CA) Akt significantly enhanced
      proteoglycan synthesis, whereas both dominant negative Akt and CA MEK inhibited
      proteoglycan synthesis. CA Akt also promoted type II collagen and Sox9
      expression, whereas tBHP treatment and CA MEK inhibited aggrecan, collagen II,
      and Sox9 mRNA expression. In osteoarthritic chondrocytes, the antioxidants
      Mn(III) tetrakis(4-benzoic acid)porphyrin and N-acetylcysteine increased the
      ratio of Akt to ERK phosphorylation and promoted IGF-I-mediated proteoglycan
      synthesis. Chemical inhibition of ERK significantly enhanced IGF-I
      phosphorylation of Akt and alleviated tBHP inhibition of Akt phosphorylation.
      These results demonstrate opposing roles for phosphatidylinositol 3-kinase-Akt
      and MEK-ERK in cartilage matrix synthesis and suggest that elevated levels of
      reactive oxygen species cause chondrocyte IGF-I resistance by altering the
      balance of Akt to ERK activity.

PMID- 19762916
TI  - Identification and characterization of the human xylosyltransferase I gene
      promoter region.
AB  - Human xylosyltransferase I catalyzes the initial and rate-limiting step in the
      biosynthesis of glycosaminoglycans and proteoglycans. Furthermore, this enzyme
      has been shown to play a major role in the physiological development of bone and
      cartilage as well as in pathophysiological processes such as systemic sclerosis,
      dilated cardiomyopathy, or fibrosis. Here, we report for the first time the
      identification and characterization of the XYLT1 gene promoter region and
      important transcription factors involved in its regulation. Members of the
      activator protein 1 (AP-1) and specificity protein 1 (Sp1) family of
      transcription factors are necessary for the transcriptional regulation of the
      XYLT1 gene, which was proven by curcumin, tanshinone IIA, mithramycin A, and
      short interference RNA treatment. A stepwise 5' and 3' deletion of the predicted
      GC-rich promoter region, which lacks a TATA and/or CAAT box, revealed that a 531
      bp core promoter element is able to drive the transcription on a basal level. A
      binding site for transcription factors of the AP-1 family, which is essential for
      full promoter activity, was identified by site-directed mutagenesis located 730
      bp 5' of the translation initiation site. The ability of this site to bind
      members of the AP-1 family was further verified by electrophoretic mobility shift
      assays. A promoter element containing this binding site was able to drive the
      transcription to about 79-fold above control in SW1353 chondrosarcoma cells. Our
      findings provide a first insight into the regulation of the XYLT1 gene and may
      contribute to understanding the processes taking place during extracellular
      matrix formation and remodeling in health and disease.

PMID- 19762917
TI  - Missense mutations that cause Bruck syndrome affect enzymatic activity, folding,
      and oligomerization of lysyl hydroxylase 2.
AB  - Bruck syndrome is a rare autosomal recessive connective tissue disorder
      characterized by fragile bones, joint contractures, scoliosis, and osteoporosis.
      The telopeptides of bone collagen I are underhydroxylated in these patients,
      leading to abnormal collagen cross-linking. Three point mutations in lysyl
      hydroxylase (LH) 2, the enzyme responsible for the hydroxylation of collagen
      telopeptides, have been identified in Bruck syndrome. As none of them affects the
      residues known to be critical for LH activity, we studied their consequences at
      the molecular level by analyzing the folding and catalytic properties of the
      corresponding mutant recombinant polypeptides. Folding and oligomerization of the
      R594H and G597V mutants were abnormal, and their activity was reduced by >95%
      relative to the wild type. The T604I mutation did not affect the folding
      properties, although the mutant retained only approximately 8% activity under
      standard assay conditions. As the reduced activity was caused by a 10-fold
      increase in the K(m) for 2-oxoglutarate, the mutation interferes with binding of
      this cosubstrate. In the presence of a saturating 2-oxoglutarate concentration,
      the activity of the T604I mutant was approximately 30% of that of the wild type.
      However, the T604I mutant did not generate detectable amounts of hydroxylysine in
      the N-terminal telopeptide of a recombinant procollagen I chain when coexpressed
      in insect cells. The low activity of the mutant LH2 polypeptides is in accordance
      with the markedly reduced extent of collagen telopeptide hydroxylation in Bruck
      syndrome, with consequent changes in the cross-linking of collagen fibrils and
      severe abnormalities in the skeletal structures.

PMID- 19762918
TI  - Homocysteine supplementation attenuates the unfolded protein response in a murine
      nutritional model of steatohepatitis.
AB  - Hyperhomocysteinemia has been correlated with hepatic steatosis and activation of
      the unfolded protein response (UPR), yet a causal relationship has not been
      established. Although methionine and choline are essential components of
      homocysteine metabolism, the role of homocysteine in the pathogenesis of a
      methionine- and choline-deficient (MCD) diet remains unknown. We explored the
      effects of homocysteine supplementation on hepatic steatosis and the UPR in mice
      fed a control or MCD diet. Mice fed the MCD diet developed severe
      hyperhomocysteinemia and activation of the hepatic UPR. Supplementing the MCD
      diet with homocysteine attenuated the MCD diet-induced hepatic UPR activation and
      other injurious effects of the MCD diet including hepatic cholesterol
      accumulation, weight loss, and plasma ALT elevation. Homocysteine supplementation
      replenished the MCD diet-induced depletion of hepatic S-adenosylmethionine (SAM).
      Depleting SAM in HepG2 cells using MAT1alpha siRNA or cycloleucine resulted in
      enhanced activation of the UPR upon exposure to thapsigargin. Mice fed a control
      diet supplemented with homocysteine had a 3-fold elevation in plasma homocysteine
      level by 2 weeks and 6-fold elevation by 6 weeks but demonstrated no other
      pathophysiologic change. In summary, we found that homocysteine attenuates MCD
      diet-induced hepatic UPR activation, likely via repletion of hepatic SAM.
      Furthermore, homocysteine supplementation alone does not cause hepatic steatosis
      or UPR activation despite inducing hyperhomocysteinemia. These studies indicate
      that although hyperhomocysteinemia is often associated with hepatic steatosis and
      UPR activation, these effects may be a secondary response rather than a direct
      effect of homocysteine.

PMID- 19762919
TI  - Integrin activation dynamics between the RGD-binding site and the headpiece
      hinge.
AB  - Integrins form mechanical links between the extracellular matrix and the
      cytoskeleton. Although integrin activation is known to be regulated by an
      allosteric conformational change, which can be induced from the extracellular or
      intracellular end of the molecule, little is known regarding the sequence of
      structural events by which signals propagate between distant sites. Here, we
      reveal with molecular dynamics simulations of the FnIII(10)-bound alpha(V)beta(3)
      integrin headpiece how the binding pocket and interdomain betaA/hybrid domain
      hinge on the distal end of the betaA domain are allosterically linked via a
      hydrophobic T-junction between the middle of the alpha1 helix and top of the
      alpha7 helix. The key results of this study are: 1) that this T-junction is
      induced by ligand binding and hinge opening, and thus displays bidirectionality;
      2) that formation of this junction can be accelerated by ligand-mediated force;
      and 3) how formation of this junction is inhibited by Ca(2+) in place of Mg(2+)
      at the site adjacent to the metal ion-dependent adhesion site ("ADMIDAS").
      Together with recent experimental evidence that integrin complexes can form catch
      bonds (i.e. become strengthened under force), as well as earlier evidence that
      Ca(2+) at the ADMIDAS results in lower binding affinity, these simulations
      provide a common structural model for the dynamic process by which integrins
      become activated.

PMID- 19762920
TI  - Development of stepwise osteogenesis-mimicking matrices for the regulation of
      mesenchymal stem cell functions.
AB  - An extracellular microenvironment, including an extracellular matrix (ECM), is an
      important factor in regulating stem cell differentiation. During tissue
      development, the ECM is dynamically remodeled to regulate stem cell functions.
      Here, we developed matrices mimicking ECM remodeling during the osteogenesis of
      mesenchymal stem cells (MSCs). The matrices were prepared from cultured MSCs
      controlled at different stages of osteogenesis and referred to as "stepwise
      osteogenesis-mimicking matrices." The matrices supported the adhesion and
      proliferation of MSCs and showed different effects on the osteogenesis of MSCs.
      On the matrices mimicking the early stage of osteogenesis (early stage matrices),
      the osteogenesis occurred more rapidly than did that on the matrices mimicking
      undifferentiated stem cells (stem cell matrices) and the late stage of
      osteogenesis (late stage matrices). RUNX2 was similarly expressed when MSCs were
      cultured on both the early stage and late stage matrices but decreased on the
      stem cell matrices. PPARG expression in the MSCs cultured on the late stage
      matrices was higher than for those cultured on the stem cell and early stage
      matrices. This increase of PPARG expression was caused by the suppression of the
      amount of beta-catenin and downstream signal transduction. These results
      demonstrate that the osteogenesis-mimicking matrices had different effects on the
      osteogenesis of MSCs, and the early stage matrices provided a favorable
      microenvironment for the osteogenesis.

PMID- 19762922
TI  - Bidirectional texture function modeling: a state of the art survey.
AB  - An ever-growing number of real-world computer vision applications require
      classification, segmentation, retrieval, or realistic rendering of genuine
      materials. However, the appearance of real materials dramatically changes with
      illumination and viewing variations. Thus, the only reliable representation of
      material visual properties requires capturing of its reflectance in as wide range
      of light and camera position combinations as possible. This is a principle of the
      recent most advanced texture representation, the Bidirectional Texture Function
      (BTF). Multispectral BTF is a seven-dimensional function that depends on view and
      illumination directions as well as on planar texture coordinates. BTF is
      typically obtained by measurement of thousands of images covering many
      combinations of illumination and viewing angles. However, the large size of such
      measurements has prohibited their practical exploitation in any sensible
      application until recently. During the last few years, the first BTF measurement,
      compression, modeling, and rendering methods have emerged. In this paper, we
      categorize, critically survey, and psychophysically compare such approaches,
      which were published in this newly arising and important computer vision and
      graphics area.

PMID- 19762923
TI  - Discriminative face alignment.
AB  - This paper proposes a discriminative framework for efficiently aligning images.
      Although conventional Active Appearance Models (AAMs)-based approaches have
      achieved some success, they suffer from the generalization problem, i.e., how to
      align any image with a generic model. We treat the iterative image alignment
      problem as a process of maximizing the score of a trained two-class classifier
      that is able to distinguish correct alignment (positive class) from incorrect
      alignment (negative class). During the modeling stage, given a set of images with
      ground truth landmarks, we train a conventional Point Distribution Model (PDM)
      and a boosting-based classifier, which acts as an appearance model. When tested
      on an image with the initial landmark locations, the proposed algorithm
      iteratively updates the shape parameters of the PDM via the gradient ascent
      method such that the classification score of the warped image is maximized. We
      use the term Boosted Appearance Models (BAMs) to refer to the learned shape and
      appearance models, as well as our specific alignment method. The proposed
      framework is applied to the face alignment problem. Using extensive
      experimentation, we show that, compared to the AAM-based approach, this framework
      greatly improves the robustness, accuracy, and efficiency of face alignment by a
      large margin, especially for unseen data.

PMID- 19762924
TI  - Face photo-sketch synthesis and recognition.
AB  - In this paper, we propose a novel face photo-sketch synthesis and recognition
      method using a multiscale Markov Random Fields (MRF) model. Our system has three
      components: 1) given a face photo, synthesizing a sketch drawing; 2) given a face
      sketch drawing, synthesizing a photo; and 3) searching for face photos in the
      database based on a query sketch drawn by an artist. It has useful applications
      for both digital entertainment and law enforcement. We assume that faces to be
      studied are in a frontal pose, with normal lighting and neutral expression, and
      have no occlusions. To synthesize sketch/photo images, the face region is divided
      into overlapping patches for learning. The size of the patches decides the scale
      of local face structures to be learned. From a training set which contains photo
      sketch pairs, the joint photo-sketch model is learned at multiple scales using a
      multiscale MRF model. By transforming a face photo to a sketch (or transforming a
      sketch to a photo), the difference between photos and sketches is significantly
      reduced, thus allowing effective matching between the two in face sketch
      recognition. After the photo-sketch transformation, in principle, most of the
      proposed face photo recognition approaches can be applied to face sketch
      recognition in a straightforward way. Extensive experiments are conducted on a
      face sketch database including 606 faces, which can be downloaded from our Web
      site (http://mmlab.ie.cuhk.edu.hk/facesketch.html).

PMID- 19762925
TI  - Face relighting from a single image under arbitrary unknown lighting conditions.
AB  - In this paper, we present a new method to modify the appearance of a face image
      by manipulating the illumination condition, when the face geometry and albedo
      information is unknown. This problem is particularly difficult when there is only
      a single image of the subject available. Recent research demonstrates that the
      set of images of a convex Lambertian object obtained under a wide variety of
      lighting conditions can be approximated accurately by a low-dimensional linear
      subspace using a spherical harmonic representation. Moreover, morphable models
      are statistical ensembles of facial properties such as shape and texture. In this
      paper, we integrate spherical harmonics into the morphable model framework by
      proposing a 3D spherical harmonic basis morphable model (SHBMM). The proposed
      method can represent a face under arbitrary unknown lighting and pose simply by
      three low-dimensional vectors, i.e., shape parameters, spherical harmonic basis
      parameters, and illumination coefficients, which are called the SHBMM parameters.
      However, when the image was taken under an extreme lighting condition, the
      approximation error can be large, thus making it difficult to recover albedo
      information. In order to address this problem, we propose a subregion-based
      framework that uses a Markov random field to model the statistical distribution
      and spatial coherence of face texture, which makes our approach not only robust
      to extreme lighting conditions, but also insensitive to partial occlusions. The
      performance of our framework is demonstrated through various experimental
      results, including the improved rates for face recognition under extreme lighting
      conditions.

PMID- 19762926
TI  - Rotation invariant kernels and their application to shape analysis.
AB  - Shape analysis requires invariance under translation, scale, and rotation.
      Translation and scale invariance can be realized by normalizing shape vectors
      with respect to their mean and norm. This maps the shape feature vectors onto the
      surface of a hypersphere. After normalization, the shape vectors can be made
      rotational invariant by modeling the resulting data using complex scalar-rotation
      invariant distributions defined on the complex hypersphere, e.g., using the
      complex Bingham distribution. However, the use of these distributions is hampered
      by the difficulty in estimating their parameters and the nonlinear nature of
      their formulation. In the present paper, we show how a set of kernel functions
      that we refer to as rotation invariant kernels can be used to convert the
      original nonlinear problem into a linear one. As their name implies, these
      kernels are defined to provide the much needed rotation invariance property
      allowing one to bypass the difficulty of working with complex spherical
      distributions. The resulting approach provides an easy, fast mechanism for 2D &
      3D shape analysis. Extensive validation using a variety of shape modeling and
      classification problems demonstrates the accuracy of this proposed approach.

PMID- 19762927
TI  - SemiBoost: boosting for semi-supervised learning.
AB  - Semi-supervised learning has attracted a significant amount of attention in
      pattern recognition and machine learning. Most previous studies have focused on
      designing special algorithms to effectively exploit the unlabeled data in
      conjunction with labeled data. Our goal is to improve the classification accuracy
      of any given supervised learning algorithm by using the available unlabeled
      examples. We call this as the Semi-supervised improvement problem, to distinguish
      the proposed approach from the existing approaches. We design a metasemi
      supervised learning algorithm that wraps around the underlying supervised
      algorithm and improves its performance using unlabeled data. This problem is
      particularly important when we need to train a supervised learning algorithm with
      a limited number of labeled examples and a multitude of unlabeled examples. We
      present a boosting framework for semi-supervised learning, termed as SemiBoost.
      The key advantages of the proposed semi-supervised learning approach are: 1)
      performance improvement of any supervised learning algorithm with a multitude of
      unlabeled data, 2) efficient computation by the iterative boosting algorithm, and
      3) exploiting both manifold and cluster assumption in training classification
      models. An empirical study on 16 different data sets and text categorization
      demonstrates that the proposed framework improves the performance of several
      commonly used supervised learning algorithms, given a large number of unlabeled
      examples. We also show that the performance of the proposed algorithm, SemiBoost,
      is comparable to the state-of-the-art semi-supervised learning algorithms.

PMID- 19762928
TI  - Signature detection and matching for document image retrieval.
AB  - As one of the most pervasive methods of individual identification and document
      authentication, signatures present convincing evidence and provide an important
      form of indexing for effective document image processing and retrieval in a broad
      range of applications. However, detection and segmentation of free-form objects
      such as signatures from clustered background is currently an open document
      analysis problem. In this paper, we focus on two fundamental problems in
      signature-based document image retrieval. First, we propose a novel multiscale
      approach to jointly detecting and segmenting signatures from document images.
      Rather than focusing on local features that typically have large variations, our
      approach captures the structural saliency using a signature production model and
      computes the dynamic curvature of 2D contour fragments over multiple scales. This
      detection framework is general and computationally tractable. Second, we treat
      the problem of signature retrieval in the unconstrained setting of translation,
      scale, and rotation invariant nonrigid shape matching. We propose two novel
      measures of shape dissimilarity based on anisotropic scaling and registration
      residual error and present a supervised learning framework for combining
      complementary shape information from different dissimilarity metrics using LDA.
      We quantitatively study state-of-the-art shape representations, shape matching
      algorithms, measures of dissimilarity, and the use of multiple instances as query
      in document image retrieval. We further demonstrate our matching techniques in
      offline signature verification. Extensive experiments using large real-world
      collections of English and Arabic machine-printed and handwritten documents
      demonstrate the excellent performance of our approaches.

PMID- 19762929
TI  - A statistical approach to material classification using image patch exemplars.
AB  - In this paper, we investigate material classification from single images obtained
      under unknown viewpoint and illumination. It is demonstrated that materials can
      be classified using the joint distribution of intensity values over extremely
      compact neighborhoods (starting from as small as 3 ?times 3 pixels square) and
      that this can outperform classification using filter banks with large support. It
      is also shown that the performance of filter banks is inferior to that of image
      patches with equivalent neighborhoods. We develop novel texton-based
      representations which are suited to modeling this joint neighborhood distribution
      for Markov random fields. The representations are learned from training images
      and then used to classify novel images (with unknown viewpoint and lighting) into
      texture classes. Three such representations are proposed and their performance is
      assessed and compared to that of filter banks. The power of the method is
      demonstrated by classifying 2,806 images of all 61 materials present in the
      Columbia-Utrecht database. The classification performance surpasses that of
      recent state-of-the-art filter bank-based classifiers such as Leung and Malik
      (IJCV 01), Cula and Dana (IJCV 04), and Varma and Zisserman (IJCV 05). We also
      benchmark performance by classifying all of the textures present in the UIUC,
      Microsoft Textile, and San Francisco outdoor data sets. We conclude with
      discussions on why features based on compact neighborhoods can correctly
      discriminate between textures with large global structure and why the performance
      of filter banks is not superior to that of the source image patches from which
      they were derived.

PMID- 19762930
TI  - Bregman divergences and surrogates for learning.
AB  - Bartlett et al. (2006) recently proved that a ground condition for surrogates,
      classification calibration, ties up their consistent minimization to that of the
      classification risk, and left as an important problem the algorithmic questions
      about their minimization. In this paper, we address this problem for a wide set
      which lies at the intersection of classification calibrated surrogates and those
      of Murata et al. (2004). This set coincides with those satisfying three common
      assumptions about surrogates. Equivalent expressions for the members-sometimes
      well known-follow for convex and concave surrogates, frequently used in the
      induction of linear separators and decision trees. Most notably, they share
      remarkable algorithmic features: for each of these two types of classifiers, we
      give a minimization algorithm provably converging to the minimum of any such
      surrogate. While seemingly different, we show that these algorithms are offshoots
      of the same "master" algorithm. This provides a new and broad unified account of
      different popular algorithms, including additive regression with the squared
      loss, the logistic loss, and the top-down induction performed in CART, C4.5.
      Moreover, we show that the induction enjoys the most popular boosting features,
      regardless of the surrogate. Experiments are provided on 40 readily available
      domains.

PMID- 19762931
TI  - A new algorithm and system for the characterization of handwriting strokes with
      delta-lognormal parameters.
AB  - In this paper, we present a new analytical method for estimating the parameters
      of Delta-Lognormal functions and characterizing handwriting strokes. According to
      the Kinematic Theory of rapid human movements, these parameters contain
      information on both the motor commands and the timing properties of a
      neuromuscular system. The new algorithm, called XZERO, exploits relationships
      between the zero crossings of the first and second time derivatives of a
      lognormal function and its four basic parameters. The methodology is described
      and then evaluated under various testing conditions. The new tool allows a
      greater variety of stroke patterns to be processed automatically. Furthermore,
      for the first time, the extraction accuracy is quantified empirically, taking
      advantage of the exponential relationships that link the dispersion of the
      extraction errors with its signal-to-noise ratio. A new extraction system which
      combines this algorithm with two other previously published methods is also
      described and evaluated. This system provides researchers involved in various
      domains of pattern analysis and artificial intelligence with new tools for the
      basic study of single strokes as primitives for understanding rapid human
      movements.

PMID- 19762932
TI  - Optimal decision rule with class-selective rejection and performance constraints.
AB  - The problem of defining a decision rule which takes into account performance
      constraints and class-selective rejection is formalized in a general framework.
      In the proposed formulation, the problem is defined using three kinds of
      criteria. The first is the cost to be minimized, which defines the objective
      function, the second are the decision options, determined by the admissible
      assignment classes or subsets of classes, and the third are the performance
      constraints. The optimal decision rule within the statistical decision theory
      framework is obtained by solving the stated optimization problem. Two examples
      are provided to illustrate the formulation and the decision rule is obtained.

PMID- 19762933
TI  - Optimal combination of nested clusters by a greedy approximation algorithm.
AB  - Given a set of clusters, we consider an optimization problem which seeks a subset
      of clusters that maximizes the microaverage F-measure. This optimal value can be
      used as an evaluation measure of the goodness of clustering. For arbitrarily
      overlapping clusters, finding the optimal value is NP-hard. We claim that a
      greedy approximation algorithm yields the global optimal solution for clusters
      that overlap only by nesting. We present a mathematical proof of this claim by
      induction. For a family of n clusters containing a total of N objects, this
      algorithm has an {?rm O}(n;{2}) time complexity and O(N) space complexity.

PMID- 19762934
TI  - A small sphere and large margin approach for novelty detection using training
      data with outliers.
AB  - We present a small sphere and large margin approach for novelty detection
      problems, where the majority of training data are normal examples. In addition,
      the training data also contain a small number of abnormal examples or outliers.
      The basic idea is to construct a hypersphere that contains most of the normal
      examples, such that the volume of this sphere is as small as possible, while at
      the same time the margin between the surface of this sphere and the outlier
      training data is as large as possible. This can result in a closed and tight
      boundary around the normal data. To build such a sphere, we only need to solve a
      convex optimization problem that can be efficiently solved with the existing
      software packages for training ?nu?hbox{-}Support Vector Machines. Experimental
      results are provided to validate the effectiveness of the proposed algorithm.

PMID- 19762935
TI  - FINE: fisher information nonparametric embedding.
AB  - We consider the problems of clustering, classification, and visualization of high
      dimensional data when no straightforward euclidean representation exists. In this
      paper, we propose using the properties of information geometry and statistical
      manifolds in order to define similarities between data sets using the Fisher
      information distance. We will show that this metric can be approximated using
      entirely nonparametric methods, as the parameterization and geometry of the
      manifold is generally unknown. Furthermore, by using multidimensional scaling
      methods, we are able to reconstruct the statistical manifold in a low-dimensional
      euclidean space; enabling effective learning on the data. As a whole, we refer to
      our framework as Fisher Information Nonparametric Embedding (FINE) and illustrate
      its uses on practical problems, including a biomedical application and document
      classification.

PMID- 19762936
TI  - Tailored aggregation for classification.
AB  - Compression and variable selection are two classical strategies to deal with
      large-dimension data sets in classification. We propose an alternative strategy,
      called aggregation, which consists of a clustering step of redundant variables
      and a compression step within each group. We develop a statistical framework to
      define tailored aggregation methods that can be combined with selection methods
      to build reliable classifiers that benefit from the information contained in
      redundant variables. Two algorithms are proposed for ordered and nonordered
      variables, respectively. Applications to the kNN and CART algorithms are
      presented.

PMID- 19762937
TI  - Toward practical smile detection.
AB  - Machine learning approaches have produced some of the highest reported
      performances for facial expression recognition. However, to date, nearly all
      automatic facial expression recognition research has focused on optimizing
      performance on a few databases that were collected under controlled lighting
      conditions on a relatively small number of subjects. This paper explores whether
      current machine learning methods can be used to develop an expression recognition
      system that operates reliably in more realistic conditions. We explore the
      necessary characteristics of the training data set, image registration, feature
      representation, and machine learning algorithms. A new database, GENKI, is
      presented which contains pictures, photographed by the subjects themselves, from
      thousands of different people in many different real-world imaging conditions.
      Results suggest that human-level expression recognition accuracy in real-life
      illumination conditions is achievable with machine learning technology. However,
      the data sets currently used in the automatic expression recognition literature
      to evaluate progress may be overly constrained and could potentially lead
      research into locally optimal algorithmic solutions.

PMID- 19762938
TI  - Properties of silicon nanoparticles embedded in SiNx deposited by microwave
      PECVD.
AB  - In this work, silicon-rich silicon nitride (SRN) layers were deposited on a
      silicon wafer by microwave-assisted plasma-enhanced chemical vapor deposition (MW
      PECVD) using NH(3) and SiH(4) as precursor gases. The Si excess in the as
      deposited layers as determined by the Rutherford backscattering technique was
      controlled by varying the precursor gas ratio. We were able to produce silicon
      nanoparticles (Si-nps) in the silicon nitride (SiN(x)) layers upon thermal
      annealing at high temperature. Energy-filtered TEM (EFTEM), complemented by
      photoluminescence measurements, were used to identify the experimental parameters
      in order to reach a high density of well-separated Si-nps (3 nm). Our results
      show that the MW-PECVD method is a suitable deposition tool for the formation of
      Si-nps in thin SRN layers.

PMID- 19762939
TI  - Enhanced photogenerated carrier collection in hybrid films of bio-templated gold
      nanowires and nanocrystalline CdSe.
AB  - Hybrid films of bio-templated gold nanowires and chemical bath deposited
      nanocrystalline CdSe were fabricated. The conductivity of the gold nanowires
      within the hybrid material was controlled by gold electroless deposition.
      Photocurrent measurements were taken on gold nanowire films, CdSe chemical bath
      deposited films, and hybrid films. The incorporation of gold nanowires within the
      hybrid material clearly increased the extraction of photogenerated carriers
      within the CdSe. Photocurrent showed a direct correlation with gold nanowire
      conductivity.

PMID- 19762941
TI  - Analysis of the blurring in stencil lithography.
AB  - A quantitative analysis of blurring and its dependence on the stencil-substrate
      gap and the deposition parameters in stencil lithography, a high resolution
      shadow mask technique, is presented. The blurring is manifested in two ways:
      first, the structure directly deposited on the substrate is larger than the
      stencil aperture due to geometrical factors, and second, a halo of material is
      formed surrounding the deposited structure, presumably due to surface diffusion.
      The blurring is studied as a function of the gap using dedicated stencils that
      allow a controlled variation of the gap. Our results show a linear relationship
      between the gap and the blurring of the directly deposited structure. In our
      configuration, with a material source of approximately 5 mm and a source
      substrate distance of 1 m, we find that a gap size of approximately 10 microm
      enlarges the directly deposited structures by approximately 50 nm. The measured
      halo varies from 0.2 to 3 microm in width depending on the gap, the stencil
      aperture size and other deposition parameters. We also show that the blurring can
      be reduced by decreasing the nominal deposition thickness, the deposition rate
      and the substrate temperature.

PMID- 19762940
TI  - Block copolymer mediated stabilization of sub-5 nm superparamagnetic nickel
      nanoparticles in an aqueous medium.
AB  - This paper presents a facile method for decreasing the size of water dispersible
      Ni nanoparticles from 30 to 3 nm by the incorporation of a passivating surfactant
      combination of pluronic triblock copolymer and oleic acid into a wet chemical
      reduction synthesis. A detailed study revealed that the size of the Ni
      nanoparticles is not only critically governed by the concentration of the
      triblock copolymers but also dependent on the hydrophobic nature of the micelle
      core formed. The synthesized Ni nanoparticles were thoroughly characterized by
      means of transmission electron microscopy, x-ray diffraction, x-ray photoelectron
      spectroscopy and temperature and field dependent magnetic measurements, along
      with a comprehensive Fourier transform infrared spectroscopy analysis, in order
      to predict a possible mechanism of formation.

PMID- 19762942
TI  - Superparamagnetic and ferromagnetic Ni nanorod arrays fabricated on Si substrates
      using electroless deposition.
AB  - The microstructures and magnetic properties of nickel nanorods fabricated using
      an anodic alumina oxide template and electroless deposition were investigated.
      The as-deposited nanorods were found to contain nanocrystalline grains with an
      average size of approximately 2-3 nm. The temperature-dependent magnetic
      hysteresis curves indicated superparamagnetic behavior of the as-deposited rods
      as a result of the reduction of ferromagnetic crystallites. The superparamagnetic
      (SM) Ni nanorods transformed into ferromagnetic (FM) ones when annealed at 400
      degrees C. Results from dark-field transmission electron microscopy reveal that
      the microstructure of the rods tends to form a laminar structure with grain
      growth parallel to the long axis of the rods, together with the enhancement of
      ferromagnetic ordering along the same direction. The results suggest that the SM
      FM phase transition obtained is microstructure driven. The Ni nanorods
      manufactured by the electroless deposition also have the potential to serve as
      magnetic building blocks in nanoscale devices, such as high-frequency inductors.
      On-chip magnetic spiral inductors were fabricated using these nanorods, and it
      was demonstrated that the nanorods can enhance inductance up to 6 GHz.

PMID- 19762943
TI  - Three-terminal electric transport measurements on gold nano-particles combined
      with ex situ TEM inspection.
AB  - We have fabricated nanometer-spaced electrodes on electron-transparent silicon
      nitride membranes. A thin Cr/Au layer is evaporated on the backside of the
      membrane which serves as a gate electrode. Using these devices, we have performed
      three-terminal electron transport measurements on gold nano-particles at liquid
      helium temperature. Coulomb Blockade features have been observed and the
      capacitance to the gate has been extracted. After transport measurements, the
      Cr/Au back gate is removed and the devices are inspected with a transmission
      electron microscope (TEM). TEM inspection reveals the presence of a few nano
      particles in the nanogap, which is in agreement with the transport measurements.
      In addition, the nano-particle size as observed by TEM coincides with the one
      estimated from the gate capacitance value.

PMID- 19762944
TI  - Cellulose nanocrystal-filled poly(acrylic acid) nanocomposite fibrous membranes.
AB  - Nanocomposite fibrous membranes have been fabricated by electrospinning cellulose
      nanocrystal (CNC)-loaded poly(acrylic acid) (PAA) ethanol mixtures. Incorporating
      CNC in PAA significantly reduced fiber diameters and improved fiber uniformity.
      The average diameters of the as-spun nanocomposite fibers were significantly
      reduced from 349 nm to 162 nm, 141 nm, 90 nm and 69 nm at 5%, 10%, 15% and 20%
      CNC loading (by weight of a constant 4% PAA solution), respectively. CNC was well
      dispersed in the fibers as isolated rods oriented along the fiber axis and as
      spheres in the PAA matrix. The Young modulus and stress of the PAA/CNC
      nanocomposite fibers were significantly improved with increasing CNC loadings by
      up to 35-fold and 16-fold, respectively. Heat-induced esterification between the
      CNC surface hydroxyls and PAA carboxyl groups produced covalent crosslinks at the
      CNC-PAA interfaces, rendering the nanocomposite fibrous membranes insoluble in
      water, more thermally stable and far more superior in tensile strength. With 20%
      CNC, the crosslinked nanocomposite fibrous membrane exhibited a very impressive
      77-fold increase in modulus and 58-fold increase in stress.

PMID- 19762945
TI  - Self-patterning of fine metal electrodes by means of the formation of isolated
      silver nanoclusters embedded in polyaniline.
AB  - A novel self-patterning technique, which is not based on surface energy
      differentiation with low or high surface energy as used in conventional surface
      energy techniques, is presented, using polyaniline and an organometallic silver
      compound. The underlying mechanisms used to control the electrical conductivity
      of the metallic silver converted from the organometallic silver compound by a
      thermal process are also analysed, with electrical and microstructural
      characterizations. It is found that polyaniline in conjunction with the
      organometallic silver compound changes its oxidation state from the conductive
      emeraldine form to the non-conductive pernigraniline form, and silver
      nanoclusters in the presence of polyaniline do not form a continuous conductive
      network, although the sheet resistance of silver nanoclusters in the absence of
      polyaniline is as low as 4.27 +/- Omega/ square at the curing temperature of 230
      degrees C. By means of these chemical and physical traits of polyaniline and the
      organometallic silver compound, alternating conductive and non-conductive stripes
      were self-patterned without the aid of surface energy patterning techniques, the
      linewidth and nominal pitch of which went down to 23.2 +/- 0.7 microm and 40
      microm, respectively.

PMID- 19762946
TI  - Preparation and bioapplication of high-quality, water-soluble, biocompatible, and
      near-infrared-emitting CdSeTe alloyed quantum dots.
AB  - A facile method is developed for the preparation of high-quality, water-soluble,
      and near-infrared (NIR)-emitting CdSeTe alloyed quantum dots (AQdots) with L
      cysteine as the capping agent. By changing the size and the composition of AQdots
      the photoluminescent quantum yield (QY) can reach as high as 53% and the emission
      color can be tuned between visible and NIR regions (580-814 nm). Furthermore, the
      prepared NIR-emitting AQdots have been successfully applied for HL-60 cell
      imaging and glucose and cholesterol assay, which demonstrates the great potential
      of the AQdots for biological applications.

PMID- 19762947
TI  - Self-assembly of poly(o-methoxyaniline) hollow nanospheres from a polymeric acid
      solution.
AB  - Self-assembled poly(o-methoxyaniline) (POMA) hollow nanospheres were prepared in
      a solution of poly(methyl vinyl ether-alt-maleic acid) (PMVEA) by oxidative
      polymerization using ammonium persulfate as the oxidant. The weight ratio of
      PMVEA to o-methoxyaniline in the solution had a significant effect on the
      morphology of the poly(o-methoxyaniline) nanospheres as determined by scanning
      electron microscopy. The diameter of the hollow nanospheres decreased from 440 to
      210 nm with an increase in the PMVEA concentration from 1% to 5%. Freeze-fracture
      transmission electron microscopy results showed the presence of spherical
      micelles composed of PMVEA/ o-methoxyaniline prior to polymerization, which also
      decreased in size as more PMVEA was added to the solution, and can act as soft
      templates for the formation of the hollow POMA nanospheres. The POMA/PMVEA hollow
      nanospheres were characterized by means of Fourier transform infrared, UV
      visible, x-ray photoelectron spectroscopy, elemental analysis and conductivity
      measurements.

PMID- 19762948
TI  - Highly ordered palladium nanodots and nanowires from switchable block copolymer
      thin films.
AB  - We demonstrate a new approach to fabricate highly ordered arrays of nanoscopic
      palladium dots and wires using switchable block copolymer thin films. The surface
      reconstructed block copolymer templates were directly deposited with palladium
      nanoparticles from a simple aqueous solution. The preferential interaction of the
      nanoparticles with one of the blocks is mainly responsible for the lateral
      arrangement of the nanoparticles inside the pores of the templates in addition to
      the capillary forces. A subsequent stabilization by UV-irradiation followed by
      pyrolysis in air at 450 degrees C removes the polymer to produce highly ordered
      metallic nanostructures. We extended this approach to micellar films to obtain
      metallic nanostructures. This method is highly versatile as the procedure used
      here is simple, eco-friendly and provides a simple approach to fabricate a broad
      range of nanoscaled architectures with tunable lateral spacing, and can be
      extended to systems with even smaller dimensions.

PMID- 19762949
TI  - Foster resonance energy transfer in solution-processed Si-nanoparticle/carbon
      nanotube nanocomposites.
AB  - By exploiting a simple solution approach, we bound ethoxy-terminated Si
      nanoparticles to surface functionalized multi-walled carbon nanotubes (MWCNTs)
      via covalent bonds. Quenching of photoluminescence (PL) of the Si nanoparticles
      was observed once they were conjugated to the MWCNTs. Analysis of the time
      resolved PL decay and calculation indicated that Foster resonance energy transfer
      from the Si nanoparticles to the MWCNTs may be responsible for the PL quenching.
      The results suggest novel potential applications of the unique Si/MWCNT
      nanocomposites in optoelectronic devices.

PMID- 19762950
TI  - Dense arrays of ordered pyramidal quantum dots with narrow linewidth
      photoluminescence spectra.
AB  - Arrays of site-controlled, pyramidal InGaAs/GaAs quantum dots (QDs) grown by
      organo-metallic chemical vapour deposition with densities comparable to those of
      self-assembled QDs (5 x 10(9) cm(-2)) are demonstrated. The QDs exhibit high
      quality photoluminescence spectra with inhomogeneous broadening of only 6.5 meV.
      The QD dipole moment was estimated through the analysis of time-resolved
      photoluminescence measurements. Such ordered QD arrays should be useful for
      applications in active nanophotonic systems such as QD lasers, modulators and
      switches requiring high overlap of the optical modes with the QD active region.

PMID- 19762951
TI  - Low density InAs/(In)GaAs quantum dots emitting at long wavelengths.
AB  - We present research carried out on molecular beam epitaxy grown InAs/(In)GaAs
      quantum dot structures for single-photon operation at long wavelengths. The
      optical and morphological properties of the structures are studied as functions
      of quantum dot growth parameters and of the InGaAs upper confining layer
      thickness and composition. We show that low growth rate, high growth temperature
      and reduced quantum dot coverage are very effective in reducing the quantum dot
      density but, owing to In desorption effects and quantum dot size reduction, this
      result is not always concomitant with the achievement of long wavelength
      emission. To this aim, we show that the use of InGaAs upper confining layers
      allows the redshift of quantum dot emission energy without affecting their
      density. Both the thickness and composition of the InGaAs layer have to be
      carefully chosen to provide a complete coverage of quantum dots and not to exceed
      the critical thickness for plastic relaxation. Our results led to the preparation
      of quantum dot structures with densities in the low 10(9) cm(-2) range, 1.33
      microm emission at 10 K and full widths at half maximum of 22 meV.

PMID- 19762952
TI  - Is cholera disease associated with poverty?
AB  - BACKGROUND: Cholera remains a global threat and is one of the key indicators of
      social development. While the disease no longer poses a menace to countries with
      minimum standards of hygiene, it remains a serious challenge to countries where
      access to safe drinking water and adequate sanitation cannot be guaranteed. The
      objective of this work was to analyse the results obtained when contrasting the
      reports of the World Health Organization (WHO) about cholera disease with those
      of the World Bank List of economies (countries). METHODOLOGY: Data were obtained
      from reports of two international organizations, the report on cholera disease
      incidence of the World Health Organization and the World Bank's classification of
      countries attending to their income. RESULTS: We determined that low-income
      countries are more affected by cholera disease than countries with middle or high
      income. This difference was reflected in the percent of countries, the total
      number of reported cases, the number of cases per 100,000 habitants, as well as
      in the reported mortality. These results support the phrase "cholera disease is a
      disease of poverty." CONCLUSIONS: We consider that economic development is an
      important factor in the morbidity and mortality of cholera, together with
      environment, climate, culture, medical management, political intention, and the
      intrinsic factors of the system.

PMID- 19762953
TI  - Identification and genotyping of the etiological agent of tuberculous
      lymphadenitis in Ethiopia.
AB  - BACKGROUND: In Ethiopia, little has been done to assess how Mycobacterium bovis
      has contributed to human tuberculosis, though the population routinely consumes
      unpasteurized milk and raw meat. The aim of this study was to determine the
      proportion of M. tuberculosis and M. bovis as etiological agents of tuberculous
      lymphadenitis (TBLN). METHODS: Patients with lymphadenopathy (n = 171) were
      included in a cross-sectional study at Butajira Hospital, Southern Ethiopia.
      Lymph node biopsies were cultured. Patients' HIV status was identified. DNA from
      positive cultures was tested by PCR to identify M. bovis and M. tuberculosis.
      Isolates were genotyped by multiplex ligation-dependent probe amplification
      (MLPA) assay. RESULTS: Among 171 patients, 156 had culture results. Of these, 107
      (69%) were positive for M. tuberculosis complex (MTC). Six of the 10 HIV-positive
      patients were culture positive. M. tuberculosis specific sequences were
      identified in the DNA of each of 100 samples as assessed by RD10 targeted PCR,
      and each of the 95 isolates exhibited the M. tuberculosis specific TbD1 deletion
      by MLPA analysis. No M. bovis was identified. These results indicate that all the
      isolates were modern M. tuberculosis strains. Furthermore, MLPA studies confirmed
      that 42% of the isolates showed the Haarlem genotype and 12% displayed sequences
      compatible with INH resistance. No mutations conferring resistance to ethambutol
      or rifampicin were detected. CONCLUSIONS: Our data showed that M. tuberculosis
      strains had common characteristics with strains causing pulmonary TB, which
      appears to be the main etiological agent of TBLN.

PMID- 19762954
TI  - Application of PCR-based serogrouping of selected Salmonella serotypes in
      Malaysia.
AB  - BACKGROUND: Differentiation of Salmonella enterica into its serogroups is
      important for epidemiological study. The objective of the study was to apply a
      multiplex PCR targeting serogroups A, B, C1, D, E and Vi-positive strains of
      Salmonella enterica commonly found in Malaysia. A separate H-typing multiplex PCR
      which identified flagellar antigen "a", "b" or "d" was also optimized to confirm
      clinical serotypes, S. Paratyphi A and S. Typhi. METHODOLOGY: Sixty-seven
      laboratory Salmonella enterica strains were tested. Six sets of primers targeting
      defined regions of the O antigen synthesis genes (rfb gene cluster) and Vi
      antigen gene (viaB) were selected and combined into a multiplex PCR for O
      grouping. Four primers (H-for, Ha-rev, Hb-rev and Hd-rev) were used in the second
      step multiplex PCR for H-typing. The optimized mPCR assays were further evaluated
      with 58 blind-coded Salmonella strains. RESULTS: The multiplex PCR results
      obtained showed 100% concordance to the conventionally typed serogroups.
      Validation with 58 blind coded Salmonella strains yield 100% accuracy and
      specificity. CONCLUSION: Based on this study, PCR serogrouping proved to be a
      rapid, alternative method for further differentiation of Salmonella enterica.

PMID- 19762955
TI  - Invasive bacteria isolates from children with severe infections in a Nigerian
      hospital.
AB  - BACKGROUND: Little information is available about the aetiology and epidemiology
      of serious bacterial infections in Nigeria. This study determined bacterial
      isolates from blood and cerebrospinal fluid (CSF) of children presenting in the
      emergency room of a teaching hospital in Nigeria. METHOD: From October 2005 to
      December 2006, children aged two to 60 months presenting with signs of acute
      systemic infections were recruited. Blood culture and CSF specimens were
      collected and processed using standard microbiological protocols. Data were
      analysed using SPSS version 11 software. RESULTS: Two hundred and two blood and
      69 CSF samples were cultured. Fifty-five (27%) of the blood cultures yielded Gram
      negative bacilli and Gram-positive cocci in almost equal proportions. The most
      common isolates from the blood cultures were Staphylococcus aureus, 26 (12.9%)
      and atypical coliforms, 13 (6.5%). Others are Klebsiella spp, 3 (1.5%);
      Klebsiella pneumonia, 2 (1.0%); Escherichia coli, 3 (1.5%); Enterobacter
      agglomerans, 2 (1.1%); Proteus mirabilis, 2(1%); Pseudomonas spp, 2 (1.0%);
      Haemophilus influenza, 1 (1.0%); and Coagulase-negative Staphylococcus, 1 (1.0%).
      Fourteen out of 67 (20.9%) of the CSF samples yielded bacterial isolates:
      Streptococcus pneumonia, 3 (4.5%); Haemophilus influenza, 8 (11.9%); Hemophilus
      spp, 1 (1.5%); E. Coli, 1 (1.5%); and atypical coliform, 1 (1.5%). Gram-negative
      coliform isolates were predominantly resistant to penicillin based antibiotics
      and co-trimoxazole but sensitive to third-generation cephalosporins and
      quinolones. A high percentage of S. aureus isolates were multi-drug resistant.
      CONCLUSIONS: Bacterial infections contribute to the significant morbidity among
      children in our environment. S. aureus was more frequently isolated in sepsis
      while H. influenzae appears to play a major role in meningitis. Appropriate use
      of antibiotics is needed to manage affected children effectively. We also
      recommend improved vaccine coverage of children under the age of five years.

PMID- 19762956
TI  - Prognostic serum tumor necrosis factor-alpha in paediatric patients with sepsis.
AB  - OBJECTIVE: To study the association of tumor necrosis factor-alpha (TNF-alpha) in
      paediatric patients with different etiological agents and levels of sepsis.
      METHODOLOGY: Seventy-nine patients with sepsis were studied. Blood cultures,
      along with other relevant specimens, were processed for bacterial and fungal
      etiology. TNF-alpha was detected by enzyme immunoassay. RESULTS: In total, 42
      (53.2%) of the patients had a microbiologically documented cause for sepsis. Of
      the gram-negative bacilli, Escherichia coli was the most common isolate followed
      by Klebsiella pneumoniae. Enterobacter spp. Serratia marscecens as well as
      Citrobacter koseri. Streptococcus pneumoniae and Staphylococcus aureus
      predominated among the gram-positive cocci. Patients with a positive culture had
      significantly higher TNF-alpha levels than patients with a negative culture (70
      pg/ml vs. 33 pg/ml p = 0.01). Patients with a pure gram-negative infection had
      significantly higher TNF-alpha levels than those with pure gram-positive
      infection (83 pg/ml vs.52 pg/ml). The geometric mean TNF-alpha concentrations in
      patients with severe sepsis and those with late septic shock were 47 pg/ml (range
      5-2720) and 59 pg/ml (range 5-3310) respectively. CONCLUSION: TNF-alpha was
      significantly raised in culture-positive cases in general and in gram-negative
      infections in particular. It can be used as a surrogate marker of sepsis and
      aggressive treatment initiated in patients with elevated levels of TNF alpha.

PMID- 19762957
TI  - Occult HBV infection among a cohort of Nigerian adults.
AB  - OBJECTIVE: To determine markers of HBV infection and detect the presence of its
      occult infection in serum of a cohort of adult Nigerians. METHODOLOGY: The study
      involved 28 adult Nigerians with viral hepatitis (Group 1) and 28 apparently
      healthy adult Nigerians as controls (Group 2). Their sera were assayed for HBsAg,
      HBeAg, anti-HBe, anti-HBc, anti-HBs, and anti-HCV, while HBV DNA was determined
      in 15 patients with chronic hepatitis. Significance of differences between the
      patients and control subjects was assessed using Chi-square test at a 95%
      confidence level. RESULTS: Sero-detection of HBsAg, HBeAg, anti-HBe and anti-HBc
      was higher among the patients compared to the controls. HBV infection was
      diagnosed by HBsAg (89%) and a duo of HBsAg and anti-HBc (100%) among the
      patients. Similarly, eleven and four types of different patterns of HBV markers
      were observed among the respective groups. Anti-HBe (9.5%), anti-HBc (14.3%), and
      anti-HBs (9.5%) were detected among all the subjects who were sero-negative for
      HBsAg. HBV DNA was also detected in 86.7% of the 15 patients with chronic
      hepatitis, while occult HBV infection was observed in 7.2% of the patients and
      none (0%) of the controls, p < 0.05. Furthermore, HCV infection occurred among
      subjects with all the different patterns of HBV markers, except those with occult
      HBV infection and natural immunity to HBV. CONCLUSION: This study shows that
      occult HBV infection is present among Nigerian adults and determination of HBsAg,
      anti-HBc, anti-HBe, and HBV DNA will assist in its detection.

PMID- 19762958
TI  - Impact of a training intervention on use of antimicrobials in teaching hospitals.
AB  - BACKGROUND: Antimicrobials are often used inappropriately in paediatric wards of
      medical college hospitals in Bangladesh. Most of the antimicrobials are
      prescribed based on clinical grounds-signs and symptoms. This intervention study
      assessed the effectiveness of a training intervention on antimicrobials
      prescribing by physicians in paediatric wards of tertiary care level hospitals.
      METHODOLOGY: This study was conducted at medical college hospitals in Bangladesh
      during the period from 1998 through 2000. The pre-intervention survey of
      antimicrobial use was conducted during 1998 in five hospitals. The post
      intervention survey was conducted after the interactive training during the
      succeeding year in three of the original five hospitals, of which one was the
      intervention hospital and two control hospitals. A total of 3,466 admitted
      paediatric patients' treatment charts (2,171 in the pre-intervention and 1,295 in
      the post-intervention surveys) were reviewed. RESULTS: The most commonly used
      antimicrobials were ampicillin, gentamicin, amoxicillin, cloxacillin and
      ceftriaxone. Appropriate antimicrobial therapy for the most common infectious
      diseases, pneumonia and diarrhoea, increased by 16.4% and 56.8% respectively in
      the intervention hospital compared with the two control hospitals and these
      improvements were significant (p = < 0.001 and p = 0.002, for pneumonia and
      diarrhoea respectively). CONCLUSIONS: An interactive, focussed educational
      intervention, targeted at physicians, appears to have been effective in improving
      appropriate antimicrobial prescribing for the most common paediatric infectious
      diseases in a medical college hospital in Bangladesh.

PMID- 19762959
TI  - Urinary schistosomiasis in the Danjarima community in Kano, Nigeria.
AB  - BACKGROUND: Studies in northern Nigeria have suggested a linear relationship
      between urinary schistosomiasis and individual water-related activities.
      Knowledge of the perceptions of the local populace about schistosomoasis and of
      gender and cultural restrictions could be beneficial to control programmes. We
      studied the prevalence of urinary schistosomoasis and the socio-demographic
      factors associated with the disease in Danjarima community of Kano, northern
      Nigeria. METHODOLOGY: A cross-sectional survey involving 890 subjects was
      conducted in the community. Urine samples were collected and examined for ova of
      Schistosoma haematobium using sedimentation technique. A semi-structured
      questionnaire was administered to the subjects in order to determine their
      knowledge and perceptions about urinary schistosomiasis in relation to their
      cultures. RESULTS: Eggs of S. haematobium were demonstrated in 370 (41.6%) of the
      urine sampled examined. The highest prevalence rate of 54.4% infection with S.
      haematobium was recorded in Zaura sub-village while the lowest rate of 6.4% was
      observed in Sabon-Fegi. More males (55.9%) were infected than females (3.7%) and
      the difference between the infection rate in males and females was statistically
      significant (P <or= 0.01). The age group 10 to 14 years recorded the highest rate
      of infection (P <or= 0.05) in both males (80.9%) and females (10.3%). CONCLUSION:
      The lack of adequate perception on the cause of urinary schistosomiasis and
      exposure to water bodies were responsible for the high prevalence of infection in
      Danjarima.

PMID- 19762960
TI  - Tungiasis-related knowledge and treatment practices in two endemic communities in
      northeast Brazil.
AB  - BACKGROUND: Tungiasis, caused by the sand flea Tunga penetrans, is highly
      prevalent in many resource-poor communities in sub-Saharan Africa, Latin America
      and the Caribbean. Studies on knowledge and treatment practices related to
      tungiasis in affected populations are virtually nonexistent. To fill this gap, we
      performed a study in two resource-poor communities in northeast Brazil where this
      parasitic skin disease is highly prevalent. METHODOLOGY: Structured interviews
      were realized in a representative sample of household leaders in an urban slum in
      Fortaleza, capital of Ceara State (northeast Brazil), and in a traditional
      fishing village 60 km southeast of the city. RESULTS: Two hundred ninety
      household leaders were interviewed in the urban slum and 136 in the fishing
      village. Knowledge about the etiological agent of tungiasis and its transmission
      was high in both communities: 90% knew the flea as the etiological agent of
      tungiasis. Transmission of tungiasis was thought to be related to sandy soil (72%
      and 84% in the urban slum and in the fishing village, respectively), presence of
      animals (52% and 59%), walking barefoot (5% and 23%), and with the presence of
      garbage littering the area (23% and 21%). Surgical extraction of embedded sand
      fleas using unsterile sewing needles was the most commonly treatment applied (97%
      and 96%). In addition, a variety of topical products and medical ointments was
      used. Mothers were almost exclusively responsible for treatment and knowledge
      transfer to the next generation. The health sector neither provided health
      education nor treatment. CONCLUSIONS: In communities of low socio-economic status
      in northeast Brazil, knowledge on tungiasis was high, but individuals did not
      follow appropriate treatment. A reduction of intensity of infestation, bacterial
      superinfection and associated morbidity is feasible with minimum support from the
      health sector, such as supplying hypodermic needles and disinfectants to mothers,
      and targeted health education.

PMID- 19762961
TI  - High level of resistance to nalidixic acid in Salmonella enterica serovar Typhi
      in Central India.
AB  - BACKGROUND: Fluoroquinolones are the drugs of choice for the treatment of typhoid
      fever. But the recent increase in minimum inhibitory concentration (MIC) values
      of ciprofloxacin in Salmonella Typhi may result in delayed response and serious
      complications. Nalidixic acid resistance has been used as an indirect evidence of
      increased minimum inhibitory concentration for ciprofloxacin in Salmonella Typhi.
      METHODS: We evaluated the isolates received at the National Salmonella and
      Escherichia Centre for nalidixic acid and ciprofloxacin susceptibility using
      standard methods. Minimum inhibitory concentrations have also been evaluated.
      RESULTS: Ninety-six percent of the isolates were found to be nalidixic acid
      resistant while all isolates were found to be ciprofloxacin sensitive. The
      difference between minimum inhibitory concentration values of ciprofloxacin for
      nalidixic acid resistant and nalidixic acid sensitive isolates was found to be
      statistically significant. CONCLUSION: The study may be helpful in revising
      treatment strategies for the infections caused by nalidixic acid resistant
      Salmonella Typhi in the country.

PMID- 19762963
TI  - Primary tuberculous abscess of rectus femoris muscle: a case report.
AB  - Tuberculosis of skeletal muscle is very rare, especially in immunocompetent
      patients. We describe a case of tuberculous abscess of rectus femoris muscle,
      which presented as a tender ill-defined mass. Diagnosis was established by PCR
      and histology. The patient showed marked improvement with a standard four-drug
      regimen with no evidence of disease activity at the two-year follow-up.

PMID- 19762962
TI  - Comparison of a DNA based PCR method with conventional methods for the detection
      of M. tuberculosis in Jos, Nigeria.
AB  - BACKGROUND: To achieve early diagnosis and effective treatment of pulmonary
      tuberculosis, simple and sensitive methods that enhance the detection of
      Mycobacterium tuberculosis (M. tuberculosis) from clinical specimens are needed.
      This study compared the effectiveness and suitability of an insertion sequence
      (IS 6110) based polymerase chain reaction (PCR) assay with conventional methods
      for the detection of M. tuberculosis from clinical specimens in a resource
      limited setting. METHODS: Sputa from 101 HIV-positive patients and 40 clinical
      specimens (sputa, gastic wash out, ascitic fluid, pleural fluid and cerebrospinal
      fluid) collected from children (HIV status unknown), all suspected for pulmonary
      tuberculosis at the Jos University Teaching Hospital, Jos, (JUTH) Nigeria, were
      examined by Ziehl Neelsen (ZN) smear microscopy, Lowenstein Jensen's (LJ) egg
      based culture, and PCR methods for the detection of M. tuberculosis. RESULTS:
      Mycobacteria was detected in 45/101 (44.6%) of the specimens from the HIV
      positive patients and comprised of 6% ZN(+)culture(+)PCR(+), 4% ZN(
      )culture(+)PCR(-), 16% ZN(-)culture(+)PCR(+) and 19% ZN(-)culture(-)PCR(+).
      Twenty-two of forty (55%) children were positive with 0% smear microscopy; 4/40
      (10%) culture(+)PCR(+); and 18/40 (45%) culture(-)PCR(+). The sensitivity and
      specificity of the PCR for the HIV-positive patients were 85% and 74%
      respectively against 23% and 100% for ZN smear microscopy. CONCLUSION: The IS6110
      PCR is a rapid and sensitive method that is specific for the M. tuberculosis
      complex group. It is simple in our experience and increased the detection of M.
      tuberculosis from the specimens examined. We suggest its use for the detection of
      M. tuberculosis in high TB and HIV burden areas.

PMID- 19762964
TI  - Septic shock due to visceral leishmaniasis, probably transmitted from blood
      transfusion.
AB  - A case of visceral leishmaniasis (VL) in a 77-year-old woman, with renal failure
      on haemodialysis, admitted in the intensive care unit (ICU) with vascular
      instability requiring vassopressor treatment, is presented. Initially, no co
      infection could be detected. The patient initially responded well when liposomal
      amphotericin B was administered, after bone marrow demonstrated multiple intra
      cellular Leishmania amastigotes and extra-cellular promastigotes. However, the
      patient died from uncontrolled septic shock from a secondary bacterial infection,
      the tenth day of admission. To our knowledge, vascular instability has not been
      reported in VL. Moreover, non-vector transmission was also suspected in this
      case. The patient had undergone cholecystectomy three months earlier, during
      which two blood units had been transfused; IgG anti-Leishmania antibodies at a
      high titer were detected in one of the two healthy blood donors, later.

PMID- 19762965
TI  - Dam and its role in pathogenicity of Salmonella enterica.
AB  - Dam methylation is an essential factor involved in the virulence of an increasing
      number of bacterial pathogens including Salmonella enterica. Lack of Dam
      methylation causes severe attenuation in animal models. It has been proposed that
      dysregulation of Dam activity is potentially a general strategy for the
      generation of vaccines against bacterial pathogens. In this review, we focus our
      attention on the role of methylation by Dam protein in regulating bacterial gene
      expression and virulence in Salmonella enterica.

PMID- 19762966
TI  - Self-medication with antibiotics by the community of Abu Dhabi Emirate, United
      Arab Emirates.
AB  - BACKGROUND: Self-medication with antibiotics may increase the risk of
      inappropriate use and the selection of resistant bacteria. The objective of the
      study was to estimate the prevalence of self-medication with antibiotics in Abu
      Dhabi. METHODOLOGY: A validated, self-administered questionnaire was used to
      collect data. Data were analysed using descriptive statistics, and the chi-square
      test when applicable. One thousand subjects were invited to participate in the
      study. RESULTS: Eight hundred sixty questionnaires were completed, with a
      respondent rate of 86%, consisting of 66% males and 34% females. Among the 860
      participants, 485 (56%) reported the use of antibiotics within the last year.
      Amoxicillin was the antibiotic most commonly used (46.3%). The survey showed a
      significant association between antibiotics used and age group (p < 0.001). Of
      the participants surveyed, 393 (46%) stated that they intentionally use
      antibiotics as self-medication without a medical consultation, a behavior that is
      significantly affected by educational levels (p<0.001). Two hundred forty-five
      (28%) participants stored antibiotics at home. These antibiotics were mostly
      acquired from community pharmacies without prescriptions (p<0.001). CONCLUSIONS:
      The results of this study confirm that antibiotic self-medication is a relatively
      frequent problem in Abu Dhabi. Interventions are required in order to reduce the
      frequency of antibiotic misuse.

PMID- 19762967
TI  - Prevalence of vancomycin resistance and multiple drug resistance in enterococci
      in equids in North India.
AB  - INTRODUCTION: Vancomycin resistant and multi-drug-resistant enterococci are the
      major emerging pathogens in surgical, neonatal, and tertiary care units.
      METHODOLOGY: In this study, 267 enterococci from different clinical and non
      clinical samples of equine origin were tested for their antimicrobial drug
      sensitivity against 19 antimicrobials using disc diffusion method. RESULTS: A
      total of 80.2% enterococci tested were resistant to vancomycin and 99.6% to
      multiple-drugs. There was a significant association between haemolytic potential
      and vancomycin resistance (chi(2), 0.00). Enterococci isolates from healthy
      equids were significantly (chi(2), 0.04) less resistant to vancomycin than the
      isolates from clinically sick animals. Besides vancomycin sensitivity, isolates
      were also tested for 18 more antimicrobial drugs; maximum numbers of isolates
      were sensitive to imipenem (75%) followed by tetracycline (60%),
      amoxicillin+clavulanic acid (54%), and minimum for cefdinir (4%). CONCLUSION:
      More than 80% strains of enterococci of equine origin were found resistant to
      vancomycin and 99.6% were multiple-drug resistant in Northern India. High
      prevalence of VRE and MDRE in healthy equids might be a potential danger for the
      health of persons in equine contact.

PMID- 19762968
TI  - Antimicrobial resistance of Staphylococcus aureus isolated from the intensive
      care unit of a general hospital in southern Brazil.
AB  - BACKGROUND: Staphylococcus aureus is recognized as a major cause of nosocomial
      infections worldwide. The aim of this study was to evaluate the antimicrobial
      resistance of S. aureus isolates and the possible changes of the resistance
      patterns after the implementation of norms of hospital infection control.
      METHODOLOGY: During the period of 2001 to 2004, antimicrobial resistance of S.
      aureus (n = 104) isolated from patients in the intensive care unit of the
      Hospital Divina Providencia (Porto Alegre, Brazil) was determined. The progress
      of S. aureus control in this hospital through 2002, after the implementation of
      norms for infection control, was also evaluated. RESULTS: The glycopeptides
      presented larger in vitro activity against the isolates of S. aureus (100% of
      susceptibility for vancomycin and teicoplanin). The percentage of samples showing
      resistance to at least one drug was 96%, 97% and 100% for the years 2001, 2003
      and 2004, respectively. Except for ampicillin and penicillin, antimicrobial
      resistance decreased from 2001 to 2004. A total of 26 phenotypic profiles were
      identified; among them a single profile (phenotype B) was identified in all three
      years of investigation, corresponding to 50% of the isolates. The number of
      isolated S. aureus decreased the following years, totaling 50 in 2001, 34 in
      2003, and 20 in 2004. CONCLUSIONS: A reduction in the number of isolates and
      antimicrobial resistance of S. aureus from the intensive care unit was observed
      after the implementation of norms for infection control.

PMID- 19762969
TI  - Osteoarticular tuberculosis--diagnostic solutions in a disease endemic region.
AB  - BACKGROUND: We conducted a study of osteoarticular tuberculosis in patients from
      private and public settings in a disease endemic area. Our objective was to
      assess the role of mycobacterial culture and polymerase chain reaction (PCR) in
      the diagnosis of osteoarticular tuberculosis (TB) in settings where only clinical
      and imaging diagnosis form the basis for treatment. METHODOLOGY: Ninety-three
      consecutive specimens collected from clinically suspected patients of
      osteoarticular TB were screened for bacterial culture, mycobacterial culture and
      in-house nested PCR. In addition, specimens were examined by imaging and
      histopathology. Ten specimens collected from patients suffering from other bone
      diseases were included as negative controls. RESULTS: Of the 93 clinically
      suspected TB patients, mycobacterial culture was positive for Mycobacterium
      tuberculosis (MTB) in 47 (51%) patients who were confirmed as definite TB cases.
      Of the remaining patients, 16 (17%) were diagnosed as probable, 19 (20%) as
      possible, and 11 (12%) as only clinically suspected TB cases. In-house nested PCR
      was positive in 65 (70%) cases. Fifteen patients were resistant to one or more
      anti-tuberculous drugs; twelve patients were multi-drug resistant, two of whom
      were extensively drug resistant. CONCLUSION: Mycobacterial cultures using liquid
      media with susceptibility should form the backbone of management of
      osteoarticular TB. Nested PCR enhances the sensitivity if performed in addition
      to culture.

PMID- 19762970
TI  - Trend of Japanese encephalitis in North India: evidence from thirty-eight acute
      encephalitis cases and appraisal of niceties.
AB  - BACKGROUND: In the year 2005, an epidemic of Japanese encephalitis (JE) occurred
      in the northern states of India. The present study was planned to reconfirm the
      circulation of JE in the area and to assess the trend of the disease to slow down
      the burden of JE. METHODOLOGY: Surveillance was conducted to identify patients
      with acute encephalitis. Blood and cerebrospinal fluid specimens from suspected
      cases underwent pathological, serological, and demographic investigations. Viral
      testing for evidence of Japanese encephalitis virus (JEV) infection was also
      performed, either by IgM capture ELISA/RT-PCR or both. To identify circulating
      JEV strains, RT-PCR, sequencing and phylogenetic analysis was performed. Based on
      clinical cases reported between 1992 and 2008, the trend of JE infection in the
      state was analyzed to examine the dynamics of infection. RESULTS: Our
      investigations (n = 38) revealed that only 55.3% cases were positive for JE.
      Pathological examination revealed marked pleocytosis in CSF (90+/-76.9
      cells/mm(3)), and peripheral leucocytosis (64.7+/-8.86% neutrophils) with mild
      anemia. Males were more susceptible than females with a ratio of 1.63:1 and
      significant gender difference (P<0.05) was observed in patients below six years.
      In the patient group younger than six years, the rate of infection per million
      was six-fold higher (P<0.005) in males as compared to females. Our phylogenetic
      study suggests that the circulating strain during the 2005 JE epidemic was close
      to GP78, and in the future a larger epidemic may occur. CONCLUSIONS: The 2005 JE
      epidemic was possibly caused by JEV GP78 and it is spreading into newer areas.
      The trend of JE suggests that the problem in North India is escalating and larger
      epidemics may occur in the future; therefore, serious steps are necessary to
      combat JE, including the development of more efficient surveillance methods and
      differential diagnosis.

PMID- 19762971
TI  - Deletion, insertion and stop codon mutations in vif genes of HIV-1 infecting slow
      progressor patients.
AB  - BACKGROUND: Variable progression towards AIDS has been described and has been
      related to viral and host factors. Around 10% of the HIV-1 infected patients are
      slow progressors (SP), not presenting with AIDS disease signs even after more
      than 10 years of infection. Viral gene defects have been associated with the
      disease progression but more studies are still needed. METHODOLOGY: The sequence
      of vif and nef were analyzed for HIV-1 infecting 14 SP and 46 normal progressors
      (NP) patients. RESULTS: Co-circulation of a strain carrying vif deleted gene with
      the wild type strain was detected in an SP patient with more than 10 years of
      infection. Other mutations (insertion in aa 63 in one strain, two premature stop
      codons in another one) were found in viruses infecting two other patients. Except
      for the SP8 strain, which exhibited a premature stop codon in nef, no gross
      deletions or insertions were observed in nef genes of both NPs and SPs strains
      analyzed. CONCLUSIONS: Different kind of mutation: deletion, insertion and stop
      codon, were detected in 3/14 samples from SP, with co-circulation of a 195 bp vif
      deletion virus with a wild type in one of these patients. Although vif defects do
      not seem to be a frequent feature in SPs, this study illustrates the importance
      of analysing this gene, in addition to the multiple factors associated with the
      long-term non progression to AIDS.

PMID- 19762972
TI  - Human immunonodeficiency virus, hepatitis B virus and hepatitis C virus: sero
      prevalence, co-infection and risk factors among prison inmates in Nasarawa State,
      Nigeria.
AB  - BACKGROUND: Published data on HIV, HBV, and HCV in correctional facilities in
      Nigeria is scarce. We set out to establish the seroprevalence, co-infection, and
      risk factors for these infections for the first time among prison inmates in
      Nasarawa State, Nigeria. METHODOLOGY: In a cross-sectional study conducted
      between April and May, 2007, blood samples were collected from 300 male prisoners
      of a mean age of 29.2 years, in the state's four medium-security prisons (overall
      population: 587). Prior to the study, ethical clearance and informed consent were
      obtained and structured questionnaires were administered. Samples were analyzed
      for HIV, HBsAg, and HCV using anti-HIV 1+2-EIA-avicenna, Shantest-HBsAg ELISA,
      and anti-HCV-EIA-avicenna, respectively. Specimens initially reactive for HIV
      were retested with vironostika microelisa. Data were analyzed using SPSS version
      13.0. P values < or = 0.05 were considered significant. RESULTS: Of the 300
      subjects, 54 (18.0 %), 69 (23.0 %), and 37 (12.3 %) tested positive for HIV, HBV,
      and HCV, respectively. Co-infections were eight (2.7 %) for HIV/HBV and two (0.7
      %) for HBV/HCV. Those aged 21-26 years were more likely to be infected with HIV
      and HBV, while those aged 33-38 years had the highest HCV infection. Associated
      risk factors included duration in prison, previous incarceration (for HIV, HBV
      and HCV), intra-prison anal sex, multiple sex partners (for HIV and HBV),
      ignorance of transmission modes, blood transfusion, and alcohol consumption (for
      HBV and HCV). No inmate injected drugs. CONCLUSIONS: The overall outcome
      represents the need for prison-focused intervention initiatives in Nigeria.
      Injected drug use is an unlikely major transmission mode among Nigerian inmates.

PMID- 19762973
TI  - Supporting formal education to improve quality of health care provided by mothers
      of children with malaria in rural western Kenya.
AB  - BACKGROUND: Home management of malaria (HMM) has been shown to be an effective
      strategy for reducing childhood mortality from malaria. The direct and especially
      indirect costs of seeking health care from formal facilities may be substantial,
      providing a major barrier for many households. Further evaluations of HMM and
      community-based utilization of available options will help to optimize treatment
      strategies and maximize health benefits. The purpose of this study was to
      determine the effect of education, occupation, and family income on the choice of
      health care options for malaria. METHODOLOGY: This was a cross-sectional,
      community-based study conducted between November 2007 and December 2007, using
      quantitative data collection methods. Mothers of children aged younger than five
      years were interviewed using a questionnaire to elicit responses on the mothers'
      level of education, occupation, income and malaria health care options. RESULTS:
      A total of 240 mothers of children aged younger than 5 years were interviewed
      between November and December, 2007. There was a direct relationship between
      formal education and occupation. The mean monthly family income was highest among
      those employed (KSh. 14,421) followed by businesswomen (KSh. 3,106) and farmers
      (KSh. 1,827) respectively (p<0.01). Those employed were more likely to take their
      ill children to a health facility (p = 0.05) or choose an antimalarial drug for
      home treatment. CONCLUSION: Supporting formal education may scale up the income
      of family health care providers and improve the quality of HMM among children
      living in rural communities.

PMID- 19762974
TI  - Phenotypic characterization of nosocomial isolates of Staphylococcus aureus with
      reference to MRSA.
AB  - BACKGROUND: Apart from being a major cause of mortality, nosocomial infections
      due to Staphylococcus aureus have been imposing a burden on patients, hospitals
      and health care systems. The present study was designed to determine the
      prevalence of methicillin resistant S. aureus (MRSA) among nosocomial isolates
      along with their phenotypic characterization. METHODOLOGY: MRSA and methicillin
      sensitive S. aureus (MSSA) were determined by performing four different tests
      viz: disc diffusion, oxacillin screen agar test, MRSA latex agglutination test,
      and MIC of oxacillin by E test. RESULTS: Of the 149 S. aureus nosocomial
      isolates, 44.9% were MRSA, which included 82.1% of homogeneous MRSA and 17.9% of
      heterogeneous MRSA. Association of MRSA infection was found to be significantly
      higher in skin and lower respiratory tract infections. Of the MRSA isolates, 65
      were multiresistant oxacillin resistant Staphylococcus aureus (MORSA) and 2 were
      nonmultiresistant oxacillin resistant Staphylococcus aureus (NORSA). D tests
      performed on 136 isolates showed that Inducible macrolide-lincosamide
      streptogramin B (MLSB) and constitutive MLSB resistance were found to be
      associated with MRSA. On the contrary, susceptibility to both erythromycin and
      clindamycin was found to be associated with MSSA. However, MSB (macrolide
      streptogramin B) resistance was not found associated either with MRSA or MSSA.
      Furthermore, both inducible and constitutive MLSB were found to be associated
      with only homogenous MRSA. CONCLUSION: D tests may be made mandatory in all S.
      aureus isolates as inducible MLSB resistance cannot be detected in routine
      susceptibility test unless erythromycin and clindamycin are placed 15-26 mm
      apart.

PMID- 19762975
TI  - Failure to demonstrate Babesia, Anaplasma or Ehrlichia in thrombocytopenic dogs
      from St Kitts.
AB  - BACKGROUND: Thrombocytopenia is common in dogs on St Kitts but there is no data
      on the possible etiological role played by infections with Anaplasma, Babesia and
      Ehrlichia, other than E. canis, which are known to occur in the Caribbean.
      METHODOLOGY: Blood from 13 thrombocytopenic but apparently healthy dogs
      seronegative (Snap 3Dx) for E. canis were tested by PCR for Ehrlichia, Anaplasma
      and Babesia. RESULTS: All PCRs were negative. CONCLUSIONS: The results confirm
      the high sensitivity of SNAP testing for E. canis and indicate Anaplasma and
      Babesia are not important causes of thrombocytopenia in dogs on St Kitts.

PMID- 19762976
TI  - Sacroiliitis caused by Salmonella typhi.
AB  - Although the commonest manifestation of Salmonella infection is acute
      gastroenteritis, infection may spread to the blood-stream may and the illness can
      present with focal lesions in almost any organ with or without septicemia. We
      describe here a case of Salmonella typhi infection of a sacroiliac joint that was
      cured with ciprofloxacin therapy for six weeks. The patient was immunologically
      normal. Salmonella etiology was not suspected in this case, and the diagnosis was
      made only after bacterial isolation. Physicians should be aware of this rare
      manifestation of Salmonella infection, especially in endemic areas.

PMID- 19762977
TI  - Isolated ulcerative skin lesion caused by Salmonella Weltevreden.
AB  - Salmonella enterica serovar Weltevreden is not a commonly isolated serotype in
      India. We report isolation of Salmonella Weltevreden, from an unusual site--an
      ulcer on the gluteal region of a patient who had undergone coronary artery bypass
      surgery. To our knowledge, Salmonellae have never been reported to cause isolated
      ulcerative lesions on the skin. This is the first report of an isolated
      ulcerative lesion on the skin caused by Salmonella Weltevreden. Our findings
      indicate that there may be modes of pathogenesis of Salmonella infections that we
      are yet unaware of. Further work and extensive reporting of all Salmonella
      infections are necessary to elucidate these mechanisms.

PMID- 19762978
TI  - Detection of Cryptococcus neoformans in faecal matter: a novel presentation of
      disseminated cryptococcosis.

PMID- 19762979
TI  - Preparing for the threat of a pandemic: a Canadian student's perspective.
AB  - Emerging infectious diseases, such as a pandemic influenza outbreak, pose a
      threat to humans and economies worldwide. A novel course at Shantou University's
      Medical College in China has provided me and nine other Canadian students with a
      unique opportunity to learn with experts in infectious disease. We are taught in
      a small group setting and our lecture material is supplemented with hands-on
      experience in the laboratory. Being placed in China offers us a distinct
      perspective on culture and social factors and their role in disease transmission
      mechanisms. This training course has offered me and the other students a deeper
      understanding of infectious disease in general and is likely to be an experience
      that we will carry with us in our future careers. This program is a step in a
      positive direction towards promoting interest in this field of scientific study
      in Canada.

PMID- 19762980
TI  - Japanese encephalitis in mainland china.
AB  - Japanese encephalitis (JE) is a seasonal epidemic disease with a 50-year recorded
      history in China. Its characteristics can be summarized as follows: (i) it is a
      seasonal epidemic disease; approximately 90% of cases are recorded in July,
      August, and September each year. The peak of JE onset is 1 month earlier in South
      China than in the north of the country; (ii) the disease is highly sporadic. It
      is rare for more than two cases to appear simultaneously in one family; (iii)
      most affected children are under 15 years old; (iv) the disease is widely
      distributed in all areas of the nation except Qinghai Province, Xinjiang Uygur
      Autonomous, and Tibet. Due to widespread application of the JE vaccine, the
      number of JE cases has decreased significantly nationwide, from 174,932 cases of
      morbidity in 1971 to 5,097 cases in 2005.

PMID- 19762981
TI  - Effects of IgY against Candida albicans and Candida spp. Adherence and Biofilm
      Formation.
AB  - The fungal pathogen Candida albicans is an opportunistic fungal pathogen that
      causes oral and vaginal mucosal infections as well as systemic disease. The
      ability of C. albicans to adhere to host surfaces is positively correlated with
      its pathogenicity. We prepared a polyclonal anti-Candida albicans antibody in
      chicken egg yolk (anti-C. albicans IgY) and investigated its in vitro
      effectiveness in preventing C. albicans adherence and biofilm formation. Anti-C.
      albicans IgY significantly reduced the adherence of C. albicans SC5314 to human
      oral epithelial cells in a dose-dependent manner. The same effect was also
      observed in other Candida spp. including C. albicans serotype A and B. Further,
      the IgY inhibited biofilm formation of C. albicans in medium without serum, but
      the inhibition was slightly restored in medium conditioned with 10% serum. The
      data indicate that anti-C. albicans IgY cross-reacted with various Candida spp.
      and may have a protective effect against oral candidiasis and reduce the
      dissemination of Candida spp. This effect may be due to the blocking of the
      binding of Candida spp. to the host cells. However, the blocking did not play a
      role when Candida formed a germ tube in the presence of serum. Therefore, anti-C.
      albicans IgY may be considered as a prophylactic immunotherapy or possibly an
      adjunctive antifungal therapy under limited conditions.

PMID- 19762982
TI  - Isolation and characterization of two phenotypically distinct dengue type-2 virus
      isolates from the same dengue hemorrhagic Fever patient.
AB  - Dengue is the one of the most prevalent arthropod-borne viral diseases. Dengue
      virus circulates between humans and mosquitoes, and causes a wide range of
      disease in humans. To elucidate the link between the cell tropism of dengue virus
      and its pathogenesis, peripheral blood cells of infected patients were analyzed
      by flow cytometry. The dengue virus antigen was detected in peripheral CD19+
      cells (B cells) in one dengue hemorrhagic fever patient. Two dengue type-2 virus
      isolates were recovered from this patient using mosquito cell line C6/36 and
      human hematopoietic cell line K562, and designated VNHCM18-C/02 and VNHCM18-K/02,
      respectively. VNHCM18-K/02 exhibited strong binding ability and high infectivity
      to a B-lymphocyte cell line (RPMI8226) but showed poor growth in C6/36 cells,
      while VNHCM18-C/02 more efficiently and dominantly grew in C6/36 cells but did
      not efficiently bind to nor infect the B-cell line. Three amino acid differences
      were detected; one in an envelope protein (E-62) and two in nonstructural
      proteins. The distinct cell-binding to RPMI8226 was attributed to the difference
      between the two isolates in envelope protein E-62. Thus, we isolated two dengue
      type-2 virus variants with different cell-tropisms from the same patient,
      suggesting possible co-circulation in the patient.

PMID- 19762983
TI  - Interaction between enterohemorrhagic Escherichia coli O157:H7 EspFu and IRSp53
      induces dynamic membrane remodeling in epithelial cells.
AB  - Enterohemorrhagic Escherichia coli (EHEC) O157:H7 induces the formation of
      filamentous, actin-rich, pedestal-shaped structures beneath bacterial cells that
      have attached to intestinal epithelial cells. Pedestal formation requires the
      translocation of EHEC O157:H7 type III effectors. One of these type III
      effectors, EspFu, consists of an N-terminal signal sequence, which is necessary
      for the translocation of EspFu into the host cell through a type III secretion
      system, and almost identical proline-rich repeats (PRRs), which control actin
      rearrangement and increase the efficiency of actin assembly in the host cell. In
      this study, we report that insulin receptor tyrosine kinase substrate p53
      (IRSp53) in the host cell acts as a binding partner for EspFu. Co
      immunoprecipitation and fluorescence microscopy showed specific interactions
      between EspFu and IRSp53 as well as their co-localization in epithelial cells.
      Additionally, we demonstrated that the association between EspFu and IRSp53
      induces dynamic membrane remodeling in epithelial cells.

PMID- 19762984
TI  - Comparative proteomic analysis of Campylobacter jejuni cultured at 37C and 42C.
AB  - Campylobacter jejuni has the potential to thrive at 37C (e.g., in the human
      intestinal tract) and 42C (e.g., in the poultry intestinal tract). We aimed to
      determine the protein expression profiles of C. jejuni cultured at 37C and 42C in
      vitro by two-dimensional electrophoresis (2DE). The differentially expressed
      spots/proteins between C. jejuni cultured at 37C and 42C were defined when their
      expression differed by twofold. The differently expressed spots detected from C.
      jejuni cultured both on agar and in broth at 37C and 42C were subjected to
      protein identification by MALDI-TOF/TOF. Overall, 15 and 20 differentially
      expressed proteins were defined for C. jejuni cultured at the two temperatures on
      agar and in broth, respectively. All of the identified differentially expressed
      proteins could be clustered as proteins involving the metabolism, regulator
      system, periplasmic proteins and the major antigens of C. jejuni. In conclusion,
      there are subsets of proteins that are optimally expressed at 37C, which may
      contribute to the host adaptation and/or the pathogenicity in the human
      intestinal tract.

PMID- 19762985
TI  - Molecular investigation of salmonella choleraesuis and salmonella hadar strains
      isolated from humans in Turkey.
AB  - Eleven Salmonella Choleraesuis and seven Salmonella Hadar strains isolated from
      various clinical humand samples were investigated by plasmid profile analysis,
      enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC
      PCR) and pulsed-field gel electrophoresis (PFGE) in order to obtain information
      at a molecular level on the epidemiology of S. Choleraesuis and S. Hadar, which
      are significantly present in Turkey. Plasmid profile analysis showed that 10
      (90.9%) of 11 S. Choleraesuis isolates harbored one to two plasmids with sizes of
      2.0, 5.0 or 6.5 kb; and 5 (71.4%) of 7 S. Hadar isolates harbored one to three
      plasmids ranging from 2.5 to 70 kb. ERIC-PCR was performed using ERIC-2 primers;
      since isolates within each serotype showed similar band models, we concluded that
      ERIC-PCR is not suitable for differentiating isolates within the same serotype
      and for grouping into clusters. In PFGE using the AvrII enzyme, S. Choleraesuis
      isolates formed three clusters, and S. Hadar isolates formed three clusters;
      using the XbaI enzyme, S. Choleraesuis isolates formed two clusters, and S. Hadar
      isolates formed four clusters. These results showed that plasmid profile analysis
      and PFGE are reliable and discriminative methods that would complement
      antibiograms, and could contribute to the investigation of outbreak epidemiology.
      This is the first report on S. Choleraesuis and S. Hadar isolates from Turkey
      investigated by plasmid profile analysis, ERIC-PCR and PFGE methods.

PMID- 19762986
TI  - Emergence of extended-spectrum beta-lactamases in clinical isolates of Salmonella
      enterica in Tehran, Iran.
AB  - The purpose of the current study was to investigate the presence and molecular
      type(s) of extended-spectrum beta-lactamases (ESBLs) in Salmonella spp. isolates
      obtained from patients with diarrhea in hospitals of Tehran, Iran. Over a period
      of 17 months, 129 Salmonella spp. were isolated from fecal samples and tested for
      susceptibility using the Kirby-Bauer disk diffusion method; then, screening for
      ESBL-producing isolates and determination of their minimum inhibitory
      concentrations were carried out using the combined disk method and standard agar
      dilution method, respectively. The presence and type of ESBL-encoding genes were
      determined by PCR and sequence analysis. The isolates were all identified as
      Salmonella enterica of different serovars. The highest resistance in the
      collected Salmonella isolates was to nalidixic acid (45.7%), followed by
      tetracycline (43.4%), trimethoprim-sulfamethoxazole (36.4%), ampicillin (15.5%),
      and chloramphenicol (14.7%). All the isolates were susceptible to ciprofloxacin,
      gentamicin, and cefoxitin. Three S. enterica isolates were resistant to
      ampicillin, piperacillin, ceftazidime, cefotaxime, ceftriaxone, cefpodoxime,
      cephalothin, and aztreonam. PCR and DNA sequencing revealed that two of the three
      isolates harbored both a bla(CTX-M-15) and a bla(TEM) gene while the third one
      carried only a bla(CTX-M-15) gene. This is the first study providing structural
      data for a CTX-M-type beta-lactamase produced by Salmonella isolates recovered in
      Iran.

PMID- 19762987
TI  - The optimization of a rapid pulsed-field gel electrophoresis protocol for the
      typing of Acinetobacter baumannii, Escherichia coli and Klebsiella spp.
AB  - Pulsed-field gel electrophoresis (PFGE) is the most common genotyping method used
      for the typing of a number of bacterial species. Generally, investigators use
      their own custom-developed protocol, but a standardized PFGE protocol would allow
      the comparison of typing results between laboratories and the tracing of strains
      around the country. In the present study, we optimized a PFGE protocol for
      subtyping of Acinetobacter baumannii, Escherichia coli and Klebsiella spp., which
      are commonly isolated from nosocomial infections in many hospitals.
      Reproducibility of our PFGE procedure was studied three times at 2- to 3-week
      intervals. Epidemiological concordance of the optimized PFGE procedure was tested
      on seven isolates of A. baumannii from a previous outbreak and seven A. baumannii
      isolates randomly selected among the clinical isolates. The optimized PFGE
      procedure was evaluated on a total of 174 clinical isolates including 62 A.
      baumannii, 50 E. coli, and 62 Klebsiella spp. The inter-laboratory
      reproducibility of the optimized protocol was tested at four laboratories. The
      optimized procedure is completed in 28 h after culturing. It is likely to be cost
      effective, due to the reduction in the time, reagent volume and enzyme
      concentration needed. The procedure showed high concordance with epidemiological
      data. There were no non-typeable isolates among the tested bacteria. It is
      reproducible and versatile. This protocol can be used to identify outbreaks and
      monitor the spreading rate of nosocomial infections caused by the tested
      bacterial isolates. Furthermore, due to its high intra- and inter-laboratory
      reproducibility, the protocol has the potential to be useful for comparing PFGE
      fingerprinting profiles of the isolates from different settings.

PMID- 19762988
TI  - The bactericidal efficacy of a photocatalytic TiO(2) particle mixture with
      oxidizer against Staphylococcus aureus.
AB  - By proving the bactericidal effects of a low-concentration titanium dioxide
      (TiO(2)) particle mixture against Staphylococcus aureus, we hope to ultimately
      apply a mixture of this type as part of a clinical treatment regimen. A bacterial
      suspension of S. aureus 1 x 10(5) CFU/ml was added dropwise to a TiO(2) particle
      mixture (19 ppm TiO(2)) and irradiated by ultraviolet (UV) light. The colony
      forming units were counted and the bacterial survival rate was calculated. In the
      control sample, the bacterial survival rate was 83.3% even after 120 min. In the
      TiO(2) mixture + UV sample, the bacteria count dropped sharply, reaching 17.3% of
      the baseline value at 30 min and 0.4% at 60 min. TiO(2) particles dispersed in
      water mixtures are known to elicit highly efficient UV absorption and greater
      bonding to bacteria. A reaction of the TiO(2) with another oxidizer altered the
      aqueous pH and accelerated the photocatalytic chemical reaction. The TiO(2)
      particle mixture showed high antibacterial action against S. aureus even at a low
      concentration.

PMID- 19762989
TI  - An unusual autopsy case of pyogenic liver abscess caused by periodontal bacteria.
AB  - Pyogenic liver abscess (PLA) formation is thought to originate from the
      transmission of infection via three major routes including the biliary tract,
      portal vein and hepatic artery. However, about 50% of PLA cases are considered to
      be cryptogenic. Here we report an unusual autopsy case of PLA associated with
      periodontopathic bacterial infection. A 59-year-old female suddenly developed
      cardiopulmonary arrest and died. Despite macroscopic and microscopic
      examinations, the infectious routes and source of infection were unidentified,
      and the case appeared to be cryptogenic. Since this patient had suffered severe
      periodontitis for a long period of time, we investigated the involvement of
      periodontal infection in PLA formation by performing immunohistochemical
      analyses. We identified several periodontopathic bacterial species in the PLA of
      this patient, including Fusobacterium nucleatum, Treponema denticola, Prevotella
      intermedia and Porphyromonas gingivalis. Thus, we demonstrate here that
      periodontal infection is a potential source of infection in the formation of PLA.

PMID- 19762990
TI  - In vitro activity of linezolid against Mycobacterium tuberculosis strains
      isoalted from Western Turkey.
AB  - We investigated the linezolid susceptibility of Mycobacterium tuberculosis
      strains isolated from a tertiary care hospital in Izmir. A total of 67 M.
      tuberculosis strains (33 multidrug-resistant [MDR] and 34 non-MDR) were isolated
      and identified by the Tuberculosis Laboratory, Department of Microbiology and
      Clinical Microbiology, Faculty of Medicine, Ege University. The activity of
      linezolid was studied by the standard agar proportion method. For all of the
      strains, the MIC range was 0.06-1 mg/L, and the MIC(50) and MIC(90) values were
      0.5 mg/L. No differences were observed between the MDR and non-MDR isolates. In
      general, linezolid was found to be effective for both the non-MDR and MDR M.
      tuberculosis strains.

PMID- 19762991
TI  - Usefulness of phage open-reading frame typing method in an epidemiological study
      of an outbreak of methicillin-resistant Staphylococcus aureus infections.
AB  - A novel genotyping method for methicillin-resistant Staphylococcus aureus (MRSA),
      the phage open-reading frames typing (POT) method, was evaluated using 92 MRSA
      isolates collected from blood cultures between 1991 and 2003 at Nagoya University
      Hospital. These strains were divided into 64 distinct POT types, classified into
      21 genotypes by pulsed-field gel electrophoresis (PFGE) using SmaI, and analyzed
      with the DICE coefficient of 80% in dendrogram analysis, with 48 subtypes
      analyzed with the DICE coefficient of 100%. The discriminatory indices of these
      three methods were 0.988, 0.719, and 0.953, respectively. The first and second
      prevalent PFGE subtypes A1 and A2, which comprised 16 and 13 isolates recovered
      serially during the study period, were both divided into 11 distinct POT types.
      Six isolates belonging to PFGE subtype A1 were indistinguishable with POT. The
      six isolates were probably involved in an outbreak. Phenotypic analysis suggested
      that these isolates were the siblings of the New York/Japan clone which are
      prevalent in many Japanese hospitals. In conclusion, in the strain population
      studied, POT is a more rapid and discriminatory method than PFGE, and is a useful
      epidemiological tool for evaluating the available clinical information.

PMID- 19762992
TI  - Tuberculosis complicated by diabetes mellitus at shanghai pulmonary hospital,
      china.
AB  - An association between diabetes mellitus (DM) and tuberculosis (TB) has been
      implied for a long time. We previously reported that KDP type 1 diabetic rats and
      GK type 2 diabetic rats are highly susceptible to Mycobacterium tuberculosis
      infection. As a next step, we conducted a retrospective analysis of 2,141
      patients with pulmonary TB newly diagnosed during the period from 2008 to 2009 to
      evaluate the influence of DM on the drug response rate and the long-term relapse
      rate of TB. There were 203 DM patients with TB (type 1 DM, 7 [3.4%]; type 2 DM,
      196 [96.6%]). The TB relapse rate (2 years after discharge) was higher in DM
      patients than in non-diabetic patients (20% versus 5.3%). The frequency of
      multidrug-resistant-TB among DM patients with TB was higher than that among TB
      patients (17.7% versus 8.4%, P<0.01). These results suggest that the period of TB
      treatment should be prolonged, and that in the meantime the blood glucose level
      should be maintained within a reference value range.

PMID- 19762993
TI  - The effects of an hsp90 inhibitor on the paradoxical effect.
AB  - It is important to conserve the effectiveness of antifungal agents because the
      options for currently available agents are limited. Although echinocandins, which
      have been developed in recent decades, are highly active against a broad spectrum
      of fungi, one concern is their reduced activity against Candida albicans at high
      drug concentrations, which is known as the paradoxical effect. To date,
      resistance related to the paradoxical effect has not been reported in clinical
      situations, but some in vivo data suggest that the paradoxical effect potentiates
      the emergence of resistance. It is valuable to investigate the underlying
      mechanisms of as well as strategies against this paradoxical resistance. Previous
      reports imply that the paradoxical effect might be related to stress responses.
      In this study, we report that radicicol, a heat shock protein 90 (Hsp90)
      inhibitor, reduces the paradoxical effect of micafungin. We also confirm that
      radicicol reduces the tolerance to voriconazole, one of the new azoles, which is
      consistent with a previous report. Our results may therefore imply that common
      stress responses might exist in the paradoxical resistance to micafungin and also
      the tolerance to voriconazole, and may suggest that inhibiting Hsp90-related
      stress responses could help to avoid potential resistances.

PMID- 19762994
TI  - Detection of a novel recombinant norovirus from sewage water in toyama
      prefecture, Japan.
AB  - Recently, the recombination event of norovirus (NoV) has been reported with high
      frequency, suggesting that RNA recombination is a major driving force in NoV
      evolution. To assess the incidence of NoV recombination in a residential area, we
      conducted a molecular biological survey of NoVs existing in sewage water in
      Toyama Prefecture, Japan. Although GII/4 was predominantly detected in sewage
      water that was associated with a high frequency of outbreaks caused by this
      genotype, other genotypes, including two types of recombinant strain, were
      identified during the survey period. One of the recombinants is the WUG1 type,
      which was first detected in Saitama Prefecture in 2000. The other recombinant is
      a novel type derived from two parent strains of genogroup II, GII/7 for the RNA
      dependent RNA polymerase and GII/13 for the capsid. This suggests that certain
      NoVs circulating in the area are occasionally changing their genetic properties
      by recombination events.

PMID- 19762995
TI  - Epidemiology of influenza from 2007 to 2008 in naha area, okinawa prefecture:
      surveillance of rapid antigen test results.
AB  - The incidence of influenza in the Naha city area in the southernmost part of
      Japan was surveyed in 2007 and 2008. Patients who had influenza-like symptoms and
      visited one of four general hospitals in Naha City, Okinawa, Japan were included
      in this study. The nasal or throat swab samples were applied to the rapid test
      for detecting influenza A and B virus antigens. The positive rate of influenza A
      and/or B virus antigen was 26.2% (8,480/32,380). Most cases (82.9%) were
      influenza A. In 2007, influenza A cases were detected during the entire year, and
      an epidemic peak was also noted in July, while no outbreak occurred in the summer
      of 2008. The surveillance of the rapid influenza virus antigen test seemed to
      provide reliable epidemiological data. This finding warrants further study in
      this region, including study of the influences of climate and socio-behavior
      patterns of the residents in the region on influenza epidemics.

PMID- 19762996
TI  - Bacterial cell surface display: a method for studying Japanese encephalitis virus
      pathogenicity.
AB  - Infection with Japanese encephalitis virus (JEV), a mosquito-borne, neurotropic
      flavivirus, may cause acute encephalitis in humans. Recombinant Salmonella
      typhimurium BRD509 was constructed to display domain III of the envelope (E)
      protein of JEV (JEDIII) on its surface with the N-terminal domain of ice
      nucleation protein (INPN) as the display motif. Bacterial cell surface display
      was confirmed by Western blot analysis and immunohistochemical staining. Binding
      of recombinant INPN-JEDIII and JEDIII proteins to three mammalian cell lines was
      compared using a cell-binding ELISA; the human neuroblastoma cell line SK-N-SH,
      which had a low level of binding, was selected for further studies. The display
      of JEDIII on the surface of BRD509 did not significantly influence its
      invasiveness was confirmed by measuring released bacterial antigen using whole
      cell ELISA. The relative expression of an apoptosis-related gene and total DNA
      damage were assessed to investigate the effects of infection on SK-N-SH cells.
      Compared to BRD509, infection with the recombinant bacterium reduced cell damage,
      suggesting that JEDIII may limit apoptosis during the early stages of JEV
      infection. Our studies demonstrated that it is feasible to study the pathogenesis
      of JEV using the approach described.

PMID- 19762997
TI  - Detection of IgM antibodies against Legionella pneumophila serogroup 1 in
      Malaysian blood donors and patients with respiratory illnesses: evaluation of
      enzyme-linked immunosorbent assay and indirect immunofluorescence assay.

PMID- 19762998
TI  - Two parameters characterizing 2009 H1N1 swine influenza epidemic in different
      countries/regions of the world.

PMID- 19762999
TI  - Transmission dynamics of malaria in four selected ecological zones of Nigeria in
      the rainy season.
AB  - BACKGROUND: Two of the problems of malaria parasite vector control in Nigeria are
      the diversity of Anopheline vectors and large size of the country. Anopheline
      distribution and transmission dynamics of malaria were therefore compared between
      four ecotypes in Nigeria during the rainy season. METHODS: Polymerase chain
      reaction (PCR) was used in molecular identification after morphological
      identification microscopically. Enzyme linked immunosorbent assay (ELISA) was
      used for the blood meal analysis and sporozoite detection. RESULTS: Five species
      were identified out of 16,410 anophelines collected. An. gambiae s.s made up
      approximately 29.2%-36.6% of the population in each zone. All five species acted
      as vectors for P. falciparum. An. gambiae s.s had the highest sporozoite rate.
      The most infected mosquitoes were found in the rain forest. More blood meals were
      taken from bovids, except the savannah forest, where 73.3% were on humans and
      Human Blood index (HBI) was 57.3%. The Entomological inoculation rate (EIR) was a
      mean of 13.6 ib/p but was highest in the rainforest zone. CONCLUSIONS AND
      LIMITATIONS: This study demonstrates the complex distribution of anophelines and
      the considerable variations in the intensity of malaria transmission in Nigeria.
      We highlight the need to consider diverse epidemiological situations when
      planning countrywide control programmes.

PMID- 19763000
TI  - Antimicrobial resistant profile of Streptococcus pneumoniae isolated from the
      nasopharynx of secondary school students in Jos, Nigeria.
AB  - BACKGROUND: Antimicrobial resistance in Streptococcus pneumoniae has compromised
      the effectiveness of therapy for pneumococcal diseases and asymptomatic
      nasopharyngeal carriers play an important role in transmission of resistant
      strains. METHOD: Eighty-eight volunteer students attending 2 secondary schools in
      Jos, Nigeria were involved in this study to determine the antimicrobial resistant
      profile of Streptococcus pneumoniae isolated from the nasopharynx. The study
      population consisted of males and females between the ages of 15-25 years.
      Nasopharyngeal swab samples were analyzed for the presence of S. pneumoniae using
      standard bacteriological methods. The isolates were subjected to antimicrobial
      susceptibility testing using the disc diffusion method. RESULTS: S. pneumoniae
      was isolated from 37 (42.04%) of the 88 samples. Isolates showed the highest
      resistance of 12 (32.43%) to erythromycin and lowest resistance of 4 (10.81%) to
      ciprofloxacin. The resistance profiles for the 26 (70.27%) penicillin-sensitive
      and 11 (29.72%) penicillin-resistant isolates were similar. Both exhibited
      varying degrees of resistance to several groups of antimicrobials. However,
      isolates found to be resistant to penicillin showed a higher degree of resistance
      to other antimicrobial agents. CONCLUSION: This study has shown that some
      secondary school students are carriers of multiple antibiotic-resistant S.
      pneumoniae.

PMID- 19763001
TI  - Comparison of two hospital stroke scores with computerized tomography in
      ascertaining stroke type among Nigerians.
AB  - BACKGROUND: Stroke, a major cause of morbidity and mortality is on the increase
      in Nigeria, routine Computerized Tomography (CT) for all Nigerians with stroke is
      not available to most doctors, and this poses management problems. We compared
      two available clinical scores with brain CT for the differential diagnosis of
      cerebral ischemia and hemorrhage among adult Nigerians with first-ever acute
      stroke. METHODS: The study was conducted at the State Specialist Hospital
      Maiduguri. Ninety-five adult Nigerians presenting with first-ever acute stroke
      onset within 48 hours were evaluated with the Siriraj Hospital Stroke (SHS) score
      on presentation and the Guy's Hospital Stroke (GHS) score 24 hours after
      admission. CT brain scan was considered as gold standard. These two stroke scores
      were compared with the results of CT brain and sensitivity, specificity; positive
      predictive and negative values were calculated. RESULTS: Applying the recommended
      optimum cut-off points for the 2 scores, diagnoses were classified by the Guy's
      Hospital Stroke and Siriraj Hospital Stroke score as probable hemorrhagic strokes
      (49% and 25% respectively) and probable ischemic (40% and 65% respectively). The
      remainder were classified as "uncertain." The prevalence of hemorrhage diagnosed
      by gold standard (CT) was 29.5% while the prevalence of ischemic stroke diagnosed
      by CT was 54.7%. The CT brain was normal in 15.8%. Sensitivity, specificity,
      positive predictive value and negative predictive value for cerebral hemorrhage
      was 0.64, 0.48, 0.4 and 0.71 for Guy's Hospital Stroke score and 0.35, 0.73, 0.4
      and 0.68 for Siriraj Hospital Stroke score. CONCLUSION: It is evident from the
      study that these clinical scoring systems alone are not sufficient and one has to
      employ the use of computerized tomography scan in establishing stroke type in
      Nigerians with stroke.

PMID- 19763002
TI  - Endophthalmitis: magnitude, treatment and visual outcome in northwest frontier
      province of Pakistan.
AB  - BACKGROUND: Many cases of post-operative and posttraumatic endophthalmitis are
      being managed at the Khyber Institute of Ophthalmic Medical Sciences, Peshawar in
      Pakistan but no study has been done to ascertain the magnitude of the disease and
      to also evaluate the visual outcome after management. METHODS: The case notes of
      39 patients diagnosed with posttraumatic and postoperative endophthalmitis
      between May 2006 and April 2007 were analyzed and clinical characteristics
      obtained were documented and tabulated. RESULTS: During the study period, 2474
      patients were admitted in both the male and female wards. Of these, 39 (1.6%) had
      endophthalmitis due to surgical and traumatic complications. In all, 6 (12.4%)
      patients had evisceration, while 21 (53.8%) patients who had topical antibiotics
      consisting of ofloxacin, 0.1% corticosteroids, fortified cetazoline and 1%
      atropine along with intravitreal antibiotics, a combination of 0.1 mg vancomycin
      and 0.4 mg amikacin, were discharged home with a visual acuity of counting
      fingers to light perception. CONCLUSION: Endophthalmitis is a serious ocular
      complication of open globe injury and intraocular surgery. The frequency in this
      center has been noted to be very high as compared to other places. Its management
      is very challenging and often leads to devastating structural and functional
      damage to the eye; causing severe frustration to both the patient and the
      attending physician. Efforts must be made to prevent the condition.

PMID- 19763003
TI  - Tuberculosis case management and treatment outcome: assessment of the
      effectiveness of Public-Private Mix of tuberculosis programme in Kaduna State,
      Nigeria.
AB  - BACKGROUND: In an effort to increase tuberculosis (TB) case detection, the Kaduna
      State TB program in Nigeria started Public-Private Mix (PPM DOTS) in 2002. This
      study assessed and compared the TB case management practices and treatment
      outcomes of the public and private health facilities involved in the TB program.
      METHODS: A comparative cross-sectional descriptive study was carried out in 5
      private and 10 public health facilities providing TB services for at least two
      years in the four Local Governments Areas in Kaduna State where both public and
      private health facilities are involved in the TB program. The heads of the health
      facilities were interviewed and case notes of all the 492 TB patients registered
      in these facilities between January 2003 and December 2004 reviewed. RESULTS:
      Except for the lower use of sputum microscopy for diagnosis, adherence to
      national TB treatment guidelines was high in both private and public health
      facilities. The private health facilities significantly saw more TB patients, an
      average of 51 patients per health facility compared to 23 patients in the public
      health facilities. There was better completion of records in the public health
      facilities while patient contact screening was very low in both public and
      private health facilities, 13.1% and 12.2% respectively. The treatment success
      rate was higher among patients managed in the private health facilities (83.7%)
      compared to 78.6% in the public health facilities. CONCLUSION: Private health
      facilities adhere to national guidelines had higher TB patient case load and
      better treatment outcome than public health facilities in Kaduna State. PPM-DOTS
      should be scaled-up and consolidated.

PMID- 19763004
TI  - Psychological morbidity, job satisfaction and intentions to quit among teachers
      in private secondary schools in Edo-State, Nigeria.
AB  - BACKGROUND: Teachers are an inseparable corner stone of the society and their
      satisfaction will affect the quality of service they render. Poor job
      satisfaction could result in job stress and this could affect their psychological
      health. This study aims to ascertain the level, causes of job dissatisfaction,
      intentions to quit and psychological morbidity among teachers in private
      secondary schools in a developing country. METHODS: A cross-sectional study was
      conducted among teachers (392) in private secondary schools in Benin-City, Edo
      State Nigeria, between June 2003 to November 2003. A total population of 400
      teachers who had spent at least one year in the service were included in the
      study. The respondents completed a self-administered designed questionnaire and a
      standard instrument--The General Health Questionnaire (GHQ 28) RESULTS: The
      response rate was 98%. Fifty-eight (14.8%) of the respondents had psychological
      morbidity (GHQ score of 4 and above). One hundred and seventy-eight (45.4%)
      teachers were very satisfied or satisfied with their jobs. A significant number
      (45.9%) of teachers would want to quit their jobs. The proportion of teachers
      with GHQ score 4 and above increased with the level of dissatisfaction but this
      was not found to be statistically significant. Poor salary was found to be the
      main cause of job dissatisfaction and major reason for wanting to quit the job.
      CONCLUSION: This study shows a low level of job satisfaction among Nigerian
      teachers. Poor salary was the major cause of job dissatisfaction and intention to
      quit. Further work need to be done to ascertain the association of psychological
      morbidity and job dissatisfaction.

PMID- 19763005
TI  - Urinary tract infection in children with nephrotic syndrome in Kano, Nigeria.
AB  - BACKGROUND: Nephrotic syndrome is a common childhood renal disorder; the
      prevalence of Urinary tract infection (UTI) in these patients is high. The
      increased prevalence of UTI are due to immunoglobulin loss, defective T cell
      function, presence of ascites and relative malnutrition. OBJECTIVE: The study is
      to evaluate the prevalence of UTI , its etiological agents, antibiotics,
      sensitivity pattern and the outcome in children with nephrotic syndrome. METHODS:
      A prospective study of all patients with diagnosis of nephrotic syndrome from
      January 2003 to December 2006. Urine specimen were routinely obtained by clean
      catch method following careful preparation urethral orifices. The specimens were
      processed immediately. Five millimeters (5 ml) loopful of the sample were
      inoculated on a blood agar and CLED agar plates. Identification of the organism
      to species level was by using stokes disc diffusion technique. RESULTS: Forty two
      patients were studied. The mean age and SEM for males was 8.2 + 0.5 years and
      females with 7.9 + 0.8 years. The age range was two to fifteen years UTI was
      caused predominantly by Staphylococcus aureus in 67.9%, Klebsiella species
      (17.9%) and Pseudomonas (14.2%). There was high in vitro resistance of these
      organisms to nalidixic acid and ampicillin but sensitive to cefotaxime,
      ceftriazone and ciprofloxacin. CONCLUSION: It is recommend that UTI should be
      sought for in patients with nephrotic syndrome and treatment should be prompt and
      appropriate.

PMID- 19763006
TI  - Day case surgery in Nigerian children: influence of social circumstances of
      patients.
AB  - BACKGROUND: In order to achieve good results in day surgery and avoid pitfalls,
      selection of appropriate procedures and patients is required with attention given
      to the social circumstances among other considerations. The aim of this
      prospective study therefore was to evaluate the influence of the social
      circumstances of the patients on the performance of day surgery practice in our
      environment. METHOD: This was a prospective study carried out between April, 2004
      and December, 2004, during which time 88 children aged 15 years and below with
      uncomplicated inguinal hernias were treated at the Obafemi Awolowo University
      Teaching Hospitals Complex (OAUTHC). The parents of the patients were interviewed
      about their social circumstances to determine the possibility of compliance with
      postoperative instructions. The data generated were then analyzed. RESULTS: More
      than half (54.6%) of the patients were from Ile-Ife. A few came from towns
      varying in distances from 65 to 80 km and spent an average time of 75 to 90
      minutes to reach the hospital. Majority of the patients used public vehicles as a
      means of transport to and from the hospital in escort of their mothers. Despite
      the long distances and difficult traveling conditions, the parents still
      preferred day case surgery and were willing to obey postoperative instructions.
      CONCLUSION: From the findings in this study, day case surgery in children in our
      environment is feasible, despite the poor social circumstances of most of them.
      There is, however a compelling need to raise the standard of living of the people
      to enable them benefit maximally from day case surgery.

PMID- 19763007
TI  - Awareness of occupational hazards and utilization of safety measures among
      welders in Kaduna metropolis, northern Nigeria.
AB  - BACKGROUND: Welders are exposed to a variety of occupational hazards with
      untoward health effects. However, little is known of welders' awareness of health
      hazards and their adherence to safety precautions in developing countries. This
      study assessed the awareness of occupational hazards and adherence to safety
      measures among welders in Kaduna metropolis in northern Nigeria. METHODS: A
      structured questionnaire was administered on a cross-section of 330 welders in
      Kaduna metropolis in northern Nigeria. Information was sought on their socio
      demographic characteristics, their awareness of occupational hazards and
      adherence to safety measures. RESULTS: All welders were males with a mean age of
      35.7 +/- 8.4 years. The illiteracy rate was 7.6%. Overall, 257 (77.9%) of the
      welders were aware of one or more workplace hazards. This was positively
      influenced by educational attainment, age, nature of training and work
      experience. Of the 330 respondents, 282 (85.3%) had experienced one or more work
      related accidents in the preceding year. The most common injuries sustained were
      cut/injuries to the hands and fingers (38.0%), back/waist pain (19%), arc eye
      injuries/foreign bodies (17.0%), burns (14.0%), hearing impairment (7.0%),
      fractures (4.0%) and amputation (1.0%). Only 113 (34.2%) welders used one or more
      types of protective device with eye goggles (60.9%), hand gloves (50.3%) and
      boots (34.5%) being more frequently used. Regular use of safety device, shorter
      working hours and increasing experience were protective of occupational
      accidents. CONCLUSIONS: The level of awareness of occupational hazards was high
      with sub optimal utilization of protective measures against the hazards. There is
      therefore need for health and safety education of these workers for health and
      increased productivity.

PMID- 19763008
TI  - Chronic kidney disease screening and renoprotection in type 2 diabetes.
AB  - BACKGROUND: Type 2 diabetes (T2D) is a major cause of chronic kidney disease.
      Control of hypertension and the use of angiotensin converting enzyme inhibitors
      (ACEI) and/or angiotensin II receptor blockers especially in those with
      proteinuria have been shown to protect against chronic kidney disease and delay
      its progression to kidney failure. METHODS: We reviewed the medical records of
      169 patients at 12 months with a view of auditing the screening for chronic
      kidney disease and the use of renoprotective measures. RESULTS: Urinalysis was
      done in 49.1% and serum creatinine in 50.3%. No patient had glomerular filtration
      rate estimated. Seventy nine (67.6%) of the hypertensive patients were on anti
      hypertensives. ACEI was used in 49 (45.8%) of these patients BP control was
      optimal in 29.1%. CONCLUSION: There is poor adherence to guidelines on chronic
      kidney disease screening and renoprotection in T2D.

PMID- 19763009
TI  - Knowledge and practice of breast-self examination among female undergraduate
      students of Ahmadu Bello University Zaria, northwestern Nigeria.
AB  - BACKGROUND: Carcinoma of the breast is an important public health problem in
      Nigeria and studies have reported low levels of awareness and practice of breast
      self examination as an important method of prevention. Breast self examination is
      a cost-effective method of early detection of cancer of the breast especially in
      resource poor countries. We assessed knowledge and practice of breast-self
      examination (BSE) among female undergraduate students of Ahmadu Bello University
      Zaria, Nigeria. METHOD: In this study, knowledge and practice of BSE were
      examined among 221 female students aged 16-28 years old studying at Ahmadu Bello
      University Zaria using self administered questionnaires. RESULTS: It was found
      that despite nearly three quarter of the respondents (87.7%) had heard of BSE,
      only 19.0% of them were performing this examination monthly. Regarding the
      sources of information about BSE among respondents, media was found to be most
      common followed by health workers accounting for 45.5% and 32.2% respectively.
      Regular performance of BSE was significantly correlated with duration of stay in
      the University (X2 = 81.9, df = 3, P 2 = 17.4, df = 2, P CONCLUSION: We observed
      a disparity between high levels of knowledge of BSE compared to a low level of
      practice. Public health education using the media could significantly reduce the
      knowledge-practice gap and early detection of breast lump.

PMID- 19763010
TI  - Rectovaginal fistula following sexual intercourse: a case report.
AB  - Female genital fistula is an important feature of the developing countries
      gynecology. Most of the rectovaginal fistulae encountered in the tropics are due
      to obstetrics causes and genital malignancies. In developed countries, radiation
      injury and Crohn's disease are also common etiological factors. The index case is
      reported to highlight the rare situation, where a 24-year old married nullipara
      sustained low rectovaginal fistula following normal coitus. She was later
      divorced by her husband.

PMID- 19763011
TI  - Hereditary spherocytosis in a 27-year-old woman: case report.
AB  - Hereditary spherocytosis (HS) is a familial hemolytic disorder with marked
      heterogeneity of clinical features, ranging from an asymptomatic condition to a
      fulminant hemolytic anemia. Although a positive family history of spherocytosis
      increases the risk for this disorder, it may be sporadic in some cases. In severe
      cases the disorder may be detected in early childhood, but in mild cases it may
      go unnoticed until later in adult life. A 27-year-old Nigerian woman presented
      with mild anemia, jaundice, splenomegaly and a history of multiple blood
      transfusion. Blood film showed about 70% spherocytes, reticulocytosis of 6.5%,
      increased osmotic fragility test and a negative direct antiglobulin test. She was
      managed conservatively on nutritional supplements and a significant regression of
      symptoms after 6 months was achieved.

PMID- 19763012
TI  - Histiocytosis X.

PMID- 19763014
TI  - Pattern of dental diseases among subjects attending a short-term medical mission
      project in Uromi, Nigeria.

PMID- 19763013
TI  - Analysis of final year medical students' examination in surgery.

PMID- 19763015
TI  - Progression factors of carotid intima-media thickness and plaque in patients with
      long-term, early-onset type 1 diabetes mellitus in Japan: simultaneous comparison
      with diabetic retinopathy.
AB  - AIM: To evaluate carotid intima-media thickness (IMT) in patients with long-term
      early-onset type 1 diabetes, and investigate the associations between IMT,
      diabetic retinopathy and clinical characteristics. METHODS: We evaluated
      anthropometric measurements, biochemical parameters and carotid IMT.
      Ultrasonography was performed on 73 patients diagnosed with type 1 diabetes
      before 30 years of age, and who have been living with diabetes for 20 years or
      more. RESULTS: The mean max-IMT (maximal thickness of whole carotid artery) and
      IMT-Cmax (maximal thickness of common carotid artery) values were 0.94 mm and
      0.67 mm; 21 patients had proliferative diabetic retinopathy and 21 patients had
      plaque (IMT > or =1.1 mm). Age, age at diagnosis of diabetes and adolescent
      HbA(1C) level (HbA(1C) at 18 years old or the earliest measurement available)
      were higher in patients with plaque than in those without. Max-IMT was greater in
      patients with proliferative retinopathy than in those without. Similarly, there
      were significant differences in current HbA(1C) level, and the prevalence of
      hypertension and dyslipidemia. In multivariate analysis, age and dyslipidemia
      were independently associated with max-IMT and IMT-Cmax. CONCLUSIONS: Age and
      dyslipidemia were associated with IMT. In contrast, glycemic control was closely
      associated with diabetic retinopathy, but weakly associated with IMT.

PMID- 19763016
TI  - Measurement performance of reagent manufacturers by Centers for Disease Control
      and Prevention/Cholesterol Reference Method Laboratory Network lipid
      standardization specified for metabolic syndrome-focused health checkups program
      in Japan.
AB  - AIM: This study was designed to clarify the current measurement performance of 7
      reagent manufacturers for high-density lipoprotein cholesterol (HDLC), low
      density lipoprotein cholesterol (LDLC) and triglycerides (TG) specified for the
      metabolic syndrome (MetS)-focused health checkups program in Japan. METHODS:
      Twenty HDLC, 21 LDLC and 9 TG analytical reagent/instrument/calibrator systems
      (system), and combinations of reagent lots, instrument models and calibrator
      lots, underwent Centers for Disease Control and Prevention (CDC)/Cholesterol
      Reference Method Laboratory Network (CRMLN) lipid standardization. Eighty and
      100% systems were requested to achieve an accuracy of within +/-1% and +/-2% of
      the reference value, so that a clinical laboratory can meet the CDC criteria.
      RESULTS: The CDC performance criteria of HDLC, LDLC and TG require an accuracy of
      within +/-5%, +/-4% and +/-5%, respectively. For HDLC, all 20 systems met the
      criteria. Fourteen (70.0%) and 18 (90.0%) systems were within +/-1% and +/-2%,
      respectively. For LDLC, 14 (66.7%) of 21 systems met the criteria, but 7 (33.3%)
      failed. Five (23.8%) and 17 (81.0%) systems were within +/-1% and +/-2%,
      respectively. For TG, 8 of 9 systems met the criteria. Two (22.2%) and 4 (44.4%)
      systems were within +/-1% and +/-2%, respectively. The minimum and maximum
      differences of a specified sample among manufacturers were 1.6 and 11.0 mg/dL for
      HDLC, 7.8 and 33.0 mg/dL for LDLC, and 2.8 and 27.4 mg/dL for TG, respectively.
      CONCLUSION: Homogeneous HDLC methods are acceptable for MetS, but further
      accuracy improvement of homogeneous LDLC and TG methods will be needed because of
      their poor performance.

PMID- 19763017
TI  - Skeletal muscle characteristics of rats with obesity, diabetes, hypertension, and
      hyperlipidemia.
AB  - AIM: Data on the skeletal muscle characteristics of patients and animals with
      lifestyle-related diseases are limited. We investigated mRNA expression levels
      and fiber profiles in the skeletal muscles of rats with obesity, diabetes,
      hypertension, and/or hyperlipidemia. METHODS: The mRNA expression levels of
      peroxisome proliferator-activated receptors (PPARalpha and PPARdelta/beta),
      PPARgamma coactivator-1alpha (PGC-1alpha), stearoyl-CoA desaturase-1 (SCD-1),
      carnitine palmi-toyl-transferase I (CPT I), medium-chain acyl-CoA dehydrogenase
      (MCAD), and mitochondrial transcriptional factor A (TFAM) in the soleus muscles
      were compared among 15-week-old control (WR), type 2 diabetic (GK), hypertensive
      (SHR), and hyperlipidemic (CP) rats. The fiber profiles in the soleus muscles of
      these rats were also determined. RESULTS: GK rats showed lower PPARdelta/beta,
      PGC-1alpha, and MCAD expression levels than WR rats. SHR rats showed higher
      PPARalpha and MCAD and lower PPARdelta/beta expression levels than WR rats. CP
      rats showed lower PPARdelta/beta and higher SCD-1 expression levels than WR rats.
      The muscles of WR, SHR, and CP rats had low-oxidative type I and high-oxidative
      type IIA and type IIC fibers, whereas the muscle of GK rats had only low
      oxidative type I fibers. CONCLUSIONS: The skeletal muscles of rats with lifestyle
      related diseases have unique mRNA expres-sion patterns and fiber profiles
      depending on the type of disease. For example, the lower PGC-1alpha and MCAD mRNA
      expression levels in the soleus muscles of type 2 diabetic rats are associated
      with the presence of only low-oxidative type I fibers in the muscle.

PMID- 19763018
TI  - Evaluation of primary care practice in the University of Tokushima.
AB  - The shortage of medical doctors is now a serious social problem in Japan. There
      are 2.1 physicians per 1000 residents in Japan, fewer than most other OECD
      countries. Tokushima Prefecture has the second highest population of medical
      doctors in Japan, but the shortage of medical doctors in rural areas was observed
      by an uneven distribution. Primary care practice was started in the education of
      clinical clerkship for 5th grade medical students of our university since July,
      2008. They round a variety of hospitals, clinics and facilities for nursing-care
      during one week in Kaihu county where has a severe problem in the shortage of
      medical doctors in Tokushima Prefecture. In order to research the efficacy of the
      primary care practice, we have administered a questionnaire for medical students
      before and after the lecture and practice, and the intensity was estimated in
      each student by using visual analogue scale. The results showed that the practice
      was more meaningful in increasing the intensity for interest and passion for
      community medicine and medicine in remote area than the lecture. Our data
      indicate that it is important to prepare more courses to learn primary care and
      general medicine in our clinical practice system to continue the interest and
      passion in community medicine.

PMID- 19763019
TI  - Saturated fatty acids and insulin resistance.
AB  - Insulin resistance is one of the pathophysiological features of obesity and type
      2 diabetes. Recent findings have linked insulin resistance to chronic low-grade
      inflammation in white adipose tissue. Excess storage of saturated fat in white
      adipose tissue due to a modern life style causes hypertrophy and hyperplasia of
      adipocytes, which exhibit attenuated insulin signaling due to their production
      and release of saturated fatty acids. These adipocytes recruit macrophages to
      white adipose tissue and, together with them, initiate a proinflammatory
      response. Proinflammatory factors and saturated fatty acids secreted into the
      bloodstream from white adipose tissue impair insulin signaling in non-adipose
      tissues, which causes whole-body insulin resistance.

PMID- 19763021
TI  - Risk factors for radiation pneumonitis caused by whole breast irradiation
      following breast-conserving surgery.
AB  - We evaluated risk factors of radiation pneumonitis (RP) after whole breast
      irradiation following breast-conserving surgery. Four hundred and seventy-two
      cases underwent whole breast irradiation with tangential field following breast
      conserving surgery in our hospital, between January 2005 and April 2007. Of these
      cases, we performed statistical analyses for 423 breasts of 413 patients, using a
      pulmonary dose-volume histogram. Patient characteristics, treatment regimens and
      irradiation methods were included as variables in the analyses on risk factors of
      RP. As a result, 89 breasts of 84 cases (21%) were diagnosed with RP. The version
      3.0 of the NCI Common Terminology Criteria for Adverse Events was used to
      evaluate the grade of pneumonitis: 77 cases (18.2%) were diagnosed as Grade 1 RP,
      10 cases (2.3%) as Grade 2, and 2 cases (0.5%) as Grade 3. Multivariate analysis
      indicated that the significant risk factors for RP were central lung distance
      (CLD) (>1.8 cm) and the short axis length of the radiation field. The incidence
      of radiation-induced bronchiolitis obliterans organizing pneumonia (BOOP)
      syndrome significantly correlated only with CLD. The lung volume within the
      radiation field was shown to be a significant risk factor for RP and radiation
      induced BOOP syndrome.

PMID- 19763020
TI  - Low susceptibility to N-ethyl-N-nitrosourea-induced transplacental carcinogenesis
      in Long-Evans Cinnamon (LEC) rats.
AB  - The Long-Evans Cinnamon (LEC) rat, an animal model of Wilson's disease, is
      resistant to a variety of chemical carcinogenesis except liver and colon. In the
      present study, N-ethyl-N-nitrosourea (ENU)-induced transplacental carcinogenesis
      was examined in male and female LEC, Long-Evans Agouti (LEA), a sibling line of
      the LEC rat, and F344 rats (n=21). ENU was administered to pregnant rats as a
      single s.c. injection at a dose of 60 mg/kg body weight on the 17th day after
      conception. Cerebral/spinal gliomas and trigeminal/spinal nerve schwannomas
      developed in both LEA and F344 rats at 30 weeks of age, but no nervous system
      tumors developed in LEC rats, the difference being statistically significant.
      Lung adenomas also developed in LEA and F344 rats, but not in LEC rats.
      Semiquantitative RT-PCR demonstrated that metallothionein (MT)1a, MT2 and O(6)
      methylguanine-DNA methyltransferase (MGMT) mRNA levels in the liver of LEC rats
      were higher than those in F344 and LEA rats. In addition, Western blot analysis
      showed that MT (MT1 plus MT2) in the liver of LEC rats was also higher than that
      in other strains. Present results suggest that high levels of MT and/or MGMT
      contribute to the resistance to nitrosamine-induced carcinogenesis in LEC rats.

PMID- 19763022
TI  - Efficacy of intravitreal bevacizumab (Avastin) for short-term treatment of
      diabetic macular edema.
AB  - PURPOSE: To report the efficacy of intravitreal injections of bevacizumab for
      diabetic macular edema (DME) in the short-term. DESIGN: Retrospective,
      noncomparative, interventional case series. METHODS: Medical records of 20 eyes
      of 19 patients who underwent intravitreal injections of bevacizumab for
      persistent diabetic macular edema were reviewed retrospectively. All eyes
      received intravitreal injections of bevacizumab (1.25 mg/0.05 ml). The clinical
      course of best-corrected visual acuity (BCVA) using a logarithm of the minimum
      angle of resolution chart, and averaged foveal retinal thickness using an optical
      coherence tomography (OCT) were monitored for up to four weeks after the
      injection. RESULTS: BCVA at one week improved by two lines or more in six eyes
      (30%) and in nine eyes (45%) at four weeks. However, no significant improvement
      in the mean BCVA from baseline was observed at one week (P>0.05) and four weeks
      (P>0.05). Mean retinal thicknesses (RT) were 411+/-170 mum at baseline, 349+/-102
      microm at one week after the injection (P<0.05), and 380+/-159 microm at four
      weeks (P>0.05). One week after the injection, significant regression of macular
      edema was seen. However, recurrence occurred at four weeks. No complications such
      as severe vision loss, endophthalmitis, or systemic events developed. CONCLUSION:
      No changes in BCVA and RT were observed in the short-term observation after the
      intravitreal injection of bevacizumab for DME.

PMID- 19763023
TI  - Efficacy of combined photodynamic therapy and sub-Tenon's capsule injection of
      triamcinolone acetonide for age-related macular degeneration.
AB  - PURPOSE: To evaluate the efficacy of combined photodynamic therapy (PDT) and sub
      Tenon's capsule injection of triamcinolone acetonide (TA) for the treatment of
      choroidal neovascularization (CNV) in age-related macular degeneration (AMD) at 1
      year follow-up. METHODS: A total of 117 eyes with subfoveal CNV caused by AMD
      were included. Sixty-eight eyes were treated with combined PDT and sub-tenon
      injection of 20 mg TA and compared with a control group of 49 eyes treated with
      PDT alone. All patients completed 1 year follow-up. The main outcome measures
      were best-corrected visual acuity (BCVA) and retreatment frequency. RESULTS:
      There were no significant differences in age, sex, VA, lesion type, and greatest
      linear dimension between the two groups at baseline. BCVA analysis showed
      statistically no significant differences between the two groups. The PDT+TA group
      required a lower mean number of treatments (1.38 versus 1.67, P=0.032).
      CONCLUSION: Our study confirms that sub-Tenon's capsule injection of TA with PDT
      significantly reduces the retreatment frequency of PDT.

PMID- 19763024
TI  - L-DOPA inhibits nitric oxide-dependent vasorelaxation via production of reactive
      oxygen species in rat aorta.
AB  - OBJECTIVES: To clarify the underlying mechanisms of L-DOPA induced
      vasoconstriction in rat aorta. METHODS: The effect of L-DOPA on phenylephrine
      induced contractile force of blood vessels was examined in vitro using rat aortic
      ring preparations by isometric tension experiment. Involvement of nitric oxide
      (NO) in the effect of L-DOPA on vascular smooth muscle was studied by using
      N(omega)-Nitro-L-arginine (L-NNA), Sodium nitroprusside (SNP) in endothelium
      intact and endothelium-denuded aortic rings. RESULTS: L-DOPA potentiated alpha
      adrenergic receptor- and depolarization-induced vascular contraction and
      inhibited acetylcholine-induced vasorelaxation. This effect was diminished by
      pretreatment of the aortic rings with L-NNA, an inhibitor of NO synthesis, or by
      removing the endothelium from the ring preparations. In endothelium-denuded
      rings, L-DOPA inhibited exogenous NO-dependent but not cGMP-mediated
      vasorelaxation. Increases in cGMP levels in response to an NO donor were
      attenuated by L-DOPA in cultured rat aortic smooth muscle cells. L-DOPA could not
      contract rings (without endothelium) pretreated with 3-(5'-hydroxymethyl- 2'
      furyl)-1-benzyl indazole (YC-1), an activator of guanylyl cyclase, but SOD (150
      U/ml) pretreatment of rings with endothelium inhibited contraction by L-DOPA.
      CONCLUSIONS: These results suggest that L-DOPA inhibits nitric-dependent
      vasorelaxation on vascular smooth muscle cells via production of reactive oxygen
      species.

PMID- 19763025
TI  - Daily calcium intake and physical activity status in urban women living on low
      incomes in Davao, Philippines: a primary study for osteoporosis prevention.
AB  - Low calcium intake and physical inactivity are modifiable risk factors of
      osteoporosis; however, little information is available about the prevalence of
      these risk factors among urban Filipino women living on low-incomes. The present
      study, therefore, investigated daily calcium intake, main calcium sources, and
      physical activity status in this population. The study group comprised healthy
      women aged in their 30 s who had participated in our previous survey using heel
      speed of sound (SOS) measurement in Davao, Philippines. The women were stratified
      into three groups based on SOS score and 20 were randomly selected from each,
      giving 60 in total. Calcium intake was measured by direct analysis of the food
      samples collected from 3-days 24 hour-food duplicate method. Physical activity
      was estimated based on pedometer determined walking steps over 5 days. The median
      [25%, 75%] calcium intake per day was 289 [225, 434] mg. Traditional foods
      derived from local small fish and plants were the main calcium sources. The
      median walking steps per day was 8750 [6920, 10836]. Although three groups did
      not show significantly different calcium intakes and walking steps, consumption
      of low-cost small fish and plant foods could be encouraged along with walking in
      urban Filipino women living on low-incomes.

PMID- 19763026
TI  - Thallium-201 chloride scintigraphy in soft tissue tumors.
AB  - OBJECTIVE: We report the findings of Thallium-201 chloride ((201)TlCl)
      scintigraphy and consider how to use this technique to evaluate the character of
      soft tissue lesions. PATIENTS AND METHODS: We enrolled 91 consecutive patients
      (45 males and 46 females, age range 8-91-years-old). Nineteen patients were
      malignant and 72 were benign. Patients were scanned 15 minutes (early phase) and
      3 hours (delayed phase) after (201)TlCl injection. More intense uptake in the
      lesion compared to the normal side was considered as 'high', the same degree of
      uptake was considered 'iso', and decreased uptake was 'low'. The retention index
      (RI) was calculated in 9 patients in the malignant group and in 16 patients in
      the benign group. RESULTS: In malignant tumors, 15 of 19 patients showed high
      uptake in both the early and delayed phases. One malignant fibrous histiocytoma
      patient was high only in the delayed phase and 1 liposarcoma patient was high
      only in the early phase. Two liposarcoma patients showed an iso uptake in both
      phases. One of these patients was pathologically diagnosed as a myxoid type. In
      benign lesions, no lipoma showed increased uptake. All neurogenic tumors except
      for 2 demonstrated high uptake. All 3 ganglions of the lower extremities showed
      iso uptake. Most inflammatory diseases showed increased uptake. Clinically
      considered benign patients consisted of tumorous lesions or inflammatory disease.
      Only 2 patients were considered 'low', and these were diagnosed as intramuscular
      hematoma and cyst. RI was variable in both malignant and benign lesions and no
      statistically significant difference was seen between malignant and benign
      lesions by t-test (p=0.72). CONCLUSIONS: A high (201)TlCl uptake lesion is more
      frequently seen in malignant tumors, but regardless of whether the tumor is
      benign or malignant, according to the histopathological variety, the (201)TlCl
      uptake pattern can not be the only indicator to differentiate malignant from
      benign tumors. We ultimately need to evaluate the nature of tumors by a
      combination of several imaging techniques.

PMID- 19763027
TI  - Extracellular matrix with the rigidity of adipose tissue helps 3T3-L1 adipocytes
      maintain insulin responsiveness.
AB  - Despite the popularity of 3T3-L1 adipocytes as a model system of adipocytes in
      vivo, they do not carry all of the cellular functions of adipocytes in vivo. In
      this study, we investigated the effect of extracellular matrix (ECM) rigidity on
      insulin signal transduction in 3T3-L1 adipocytes. On 250 Pa polyacrylamide gel
      (soft gel) laminated with a mixture of collagen type 1 and fibronectin, whose
      rigidity matches that of adipose tissue, expression of the insulin receptor, IRS
      1 and AKT was upregulated and their insulin-stimulated phosphorylation was
      enhanced. Furthermore, the expression of GLUT1 was downregulated, whereas the
      expression of GLUT4 was unaffected as ECM rigidity decreased. Insulin-stimulated
      GLUT4 recruitment to the plasma membrane was significantly enhanced in cells
      seeded on soft gel. These results suggest that adjusting the ECM rigidity to that
      of adipose tissue augments insulin signaling in 3T3-L1 adipocytes and enhances
      insulin-stimulated GLUT4 recruitment to the plasma membrane.

PMID- 19763028
TI  - Suitability of ultraviolet (A)-light emitting diode for air stream disinfection.
AB  - We previously developed a high powered light-emitting diode device capable of
      discharging germicidal ultraviolet irradiation (UVA-LED) at an approximate
      wavelength of 365 nm. This study examined the bactericidal activity of UVA-LED in
      moving air streams. Aerosols of Escherichia coli DH5alpha were exposed to UVA-LED
      irradiation using a stable current (0.5 A and 1.2 mW/cm(2)) or pulse current (1.0
      A and 0.2 mW/cm(2)). Settle plate analysis was used for bioaerosol sampling,
      where results were expressed as Colony Forming Units. A -3 Log inactivation of
      the E. coli population occurred after 75 minutes of constant exposure to stable
      current. The pulse current produced inactivation within a similar timeframe. Our
      results might be significant as a basic study for further investigations about
      the effect of UVA-LED on airborne bacteria and its suitability for air
      disinfection applications.

PMID- 19763029
TI  - Nerve fibers that were not stained with the non-specific acetylcholinesterase
      (NsAchE) method, and TRPV1- and IB4-positive nerve fibers in the rat cornea.
AB  - Previously, we noticed the presence of nerve fiber-like structures in a whole
      mount preparation of the rat cornea that had not been stained with the non
      specific acetylcholinesterase (NsAchE) method. These nerve-like fibers were
      projected into the central area of the cornea, forming a mesh-like pattern. The
      aim of this study is to examine the properties of these mesh-like fibers using
      the following two methods: their sensitivity to capsaicin and the detection of
      isolectin B4 (IB4)- and capsaicin receptor TRPV1 (transient receptor potential
      vanilloid 1)-reactivities. The mean disappeared area of non-stained fibers after
      NsAchE treatment was 26% of the total areas in the neonatally capsaicin-treated
      cornea. Bunches composed of fine IB4-positive nerve fibers were seen in a whole
      mount preparation. There were connections between the bunches, producing a mesh
      like pattern similar to that of the fibers that were not stained with NsAchE.
      Fine TRPV1-immunoreactive (ir) nerve fibers were also shown to form bunches, with
      connections between each bunch observed in whole mount preparations. Thus, TRPV1
      ir nerve fibers seem to densely innervate the rat corneal subepithelial stroma
      and are distinct from the NsAchE-positive nerve fibers. The TRPV1-ir fine nerve
      fibers overlapped with the IB4-positive nerve fibers, suggesting that the mesh
      like fibers that were not stained with NsAchE are fine nociceptive sensory nerve
      fibers because of their sensitivity to capsaicin and similar distribution pattern
      to IB4- and TRPV1-positive nerve fibers.

PMID- 19763030
TI  - Three cases of Acanthamoeba keratitis diagnosed and treated in the early stage.
AB  - Acanthamoeba keratitis (AK) is a severe infectious corneal ulcer that usually
      occurs in contact lens wearers. Although the number of AK cases in Japan has been
      increasing, many of these cases are diagnosed in the early stage and are treated
      adequately. This is probably because of the increased availability of various
      diagnostic techniques and the ever-increasing knowledge about AK among
      ophthalmologists. In this article, we described 3 cases of AK that were diagnosed
      and treated in the early stages of the disease, and we discuss why 1 of the cases
      had a less favorable prognosis than the other 2 cases, which had excellent
      prognoses, from an etiological point of view.

PMID- 19763032
TI  - Use of dietary supplements among preschool children in Japan.
AB  - This study was conducted to examine the characteristics and use of dietary
      supplements by preschool children in Japan. A survey was conducted among 2,125
      parents of preschool children to discover the status of dietary supplement use
      and their attitudes towards supplement use by their children. Logistic regression
      models were used to determine which characteristics predict supplement use in
      this population. For detailed characterization, child supplement users were also
      categorized as either the users of vitamins and minerals only or the users of
      other supplement components. For parents of non-user children, the parent's
      knowledge and attitudes toward supplements for children were investigated.
      Fifteen percent of children had used dietary supplements. Two parent-related
      factors were especially important, the frequency with which they referred to
      nutritional labels and their own supplement use, which had a significant
      encouraging effect on their children's supplement use. The parents of child
      supplement users showed limited awareness of the government system concerning
      diet and food, placed safety over efficacy, selected products with natural
      ingredients, and did not seek consultations with professionals. These parents,
      especially those who were aware of the specially designed supplements for
      children, exhibited positive responses to supplement use by their children. It is
      likely that parents' knowledge and attitudes toward dietary supplements and
      nutrition have a striking effect on their children's use of supplements.
      Unfortunately, their knowledge at present was less than satisfactory. More
      accurate information on nutrition, dietary intake and dietary supplements must be
      disseminated.

PMID- 19763031
TI  - The status of glutathione peroxidase, superoxide dismutase, vitamins A, C, E and
      malondialdehyde in patients with cardiovascular disease in Zahedan, Southeast
      Iran.
AB  - Growing evidence has demonstrated that oxidative stress and increased altered
      oxygen utilization contribute to atherogenesis and cardiovascular disease (CVD)
      progression. Antioxidants protect the body from damage caused by free radicals.
      The objective of this study was to determine antioxidants status in CVD patients.
      This cross-sectional study was performed on 71 patients clinically diagnosed with
      CVD and 63 healthy individuals. Plasma malondialdehyde (MDA) level was measured
      for lipid peroxidation product and erythrocyte SOD and GPx activities as
      enzymatic antioxidants. The serum levels of vitamins A and E were assayed using
      HPLC and vitamin C by the photometric method. Total antioxidant capacity (TAC)
      was measured using the ferric reducing ability of plasma (FRAP) method. The
      results showed a significant reduction in antioxidant status (enzymatic and non
      enzymatic) with a concomitant increase in the concentrations of lipid
      peroxidation products in CVD patients. There was a significant inverse
      correlation among TAC, SOD, GPx and vitamin C with MDA. It can be concluded that
      the antioxidant defense system plays an important role in preventing the
      development and progression of CVD with the ability to control oxidative stress.

PMID- 19763033
TI  - Effects of soybean isoflavone on the notch signal pathway of the brain in rats
      with cerebral ischemia.
AB  - The aim of this study was to test the hypothesis that gastric lavage with soybean
      isoflavone activates the Notch signaling pathway and prevents apoptosis in the
      cerebral cortex during experimental strokes. Sprague-Dawley rats were randomly
      assigned to four groups of 10 rats each: sham operation plus vehicle (Sham),
      middle cerebral artery occlusion plus vehicle (MCAO), MCAO plus low dose soybean
      isoflavone (10 mg/(kg.d)) and MCAO plus high dose soybean isoflavone (50
      mg/(kg.d)). The vehicle (saline, 10 mL/(kg.d)) and soybean isoflavone were
      administered by gastric lavage for 28 d prior to sham or MCAO operation and for 7
      d afterward. The mRNA and protein expression levels of components of the Notch
      signaling system (Notch1 and Hes5) were measured by in situ hybridization and
      western blotting, respectively, whereas apoptosis was quantified by TUNEL assay.
      The results showed that MCAO stimulated expression of Notch1 and Hes5, at both
      the mRNA and protein levels, and also increased apoptosis. Soybean isoflavone
      dose-dependently augmented the stimulatory effect of MCAO on Notch1 and Hes5
      expression levels but decreased apoptosis. These results identify a possible
      mechanism by which soybean isoflavone confers neuroprotection in strokes.

PMID- 19763034
TI  - Absence of negative feedback on intestinal magnesium absorption on excessive
      magnesium administration in rats.
AB  - This study aimed to clarify the regulatory mechanism of Mg homeostasis on
      administration of excessive Mg in rats. Six-week-old male Wistar rats (n=30) were
      fed a Mg-deficient diet (D) or a control diet (M) in addition to which they
      received subcutaneous injections of saline (S) or additional Mg (M) for 14 d.
      Feces and urine were collected from the rats for 4 d every week. Between the MS
      and MM rats and the DS and DM rats, the injection of additional Mg increased Mg
      retention, but intestinal Mg absorption did not differ. Urinary Mg excretion in
      the MM rats was significantly greater than that in the MS rats, but fecal Mg
      excretion did not increase. Mg retention in the DM rats was approximately 30% of
      that in the MS rats, and urinary Mg excretion did not differ between the 2
      groups, although the serum Mg in DM rats was low. There was no significant
      difference in the femoral Mg between the MM and MS groups. The physiological Mg
      pool in the bone appears to be limited. Therefore, there is no physiological Mg
      pool for the storage of excessive Mg, and there appears to be no negative
      feedback mechanism on intestinal Mg absorption upon administration of excessive
      Mg in the rats. In conclusion, it appears that the kidney is the only organ that
      regulates Mg in the body; apart from this, regulatory mechanisms corresponding to
      the physiological Mg requirement do not exist or are weak.

PMID- 19763035
TI  - Nutritional status of lactating mothers and their breast milk concentration of
      iron, zinc and copper in rural Vietnam.
AB  - Breast milk is considered to be the best nutrient source for infants. However,
      nutritional compositions of breast milk in developing countries, especially among
      malnourished women, have not been fully investigated. This study aimed to assess
      nutritional status and nutrient composition of breast milk in lactating mothers
      in rural Vietnam. Sixty breastfeeding mothers at 6 to 12 mo postpartum, free from
      any medical disorder and/or medication, and not pregnant were randomly selected
      in Yen The, Bac Giang, Vietnam. Their nutritional status, breast milk
      concentration and dietary intakes were assessed. Among the study participants,
      anemia (39.0%) and low serum zinc concentration (55.4%) were frequently observed.
      Dietary assessment revealed lower intakes of iron (10.2+/-2.5 mg/d) and zinc
      (10.4+/-2.2 mg/d) than estimated requirements. The breast milk concentration of
      iron, zinc and copper was 0.43+/-0.15 mg/L, 0.56 (0.37, 0.82) mg/L and 0.19+/
      0.05 mg/L, respectively. The breast milk concentration of iron, zinc and copper
      was not correlated to the serum concentration or dietary intakes. In conclusion,
      we uncovered a high prevalence of anemia and zinc deficiency in lactating mothers
      in rural Vietnam. The findings demonstrate a low breast milk zinc concentration
      among the participants, but need further investigation.

PMID- 19763036
TI  - Effect of plant- and fish-oil derived n-3 polyunsaturated fatty acids on
      counteraction of n-3 fatty acid shortage in adult rats fed a lard diet.
AB  - These studies aimed to compare the effects of alpha-linolenic acid
      (ALA)+eicosapentaenoic acid (EPA)+docosahexaenoic acid (DHA) on plasma-lipid
      concentrations and preferential fat intake of rats fed a lard diet (LD). Each of
      2 groups of 4-wk-old male rats was used in studies 1 and 2. In studies 1 and 2,
      two groups of rats received the LD (LD group) and the fish-oil diet (FD; FD
      group), and the LD and the perilla-oil diet (PD; PD group), respectively (dietary
      treatment period). After 6 wk, 6 rats per group were sacrificed. The remaining
      rats in studies 1 and 2 were placed on a self-selection regimen of the LD and the
      FD, and the LD and the PD, respectively, for 3 wk (self-selection period). After
      the dietary treatment period, plasma lipid concentrations in the FD group were
      lower than those in the LD group. However, no significant difference in the
      concentrations was observed between the LD group and the PD group. At the
      beginning of the self-selection period, the ratio of the FD intake of the LD
      group was higher than that of the FD group. As the the ratio of the LD group
      decreased and that of the FD group increased no significant difference in the
      ratio was observed after the 9th day during the self-selection period. No
      significant difference in the ratio of the PD intake was observed between the LD
      group and the PD group during the self-selection period. Thus, although the FD
      decreased plasma lipid concentration and increased the preferential FD intake of
      the LD group at the beginning of the self-selection period, the PD did not. Our
      studies clearly show that dietary EPA+DHA and ALA have different physiologic
      effects.

PMID- 19763037
TI  - Change to a preference for maltose from sucrose over days in Zn-deficient rats
      selecting from maltose and sucrose diets.
AB  - This paper describes a preference for two disaccharides in the diets of Zn
      adequate and Zn-deficient rats. Maltose and sucrose were used as a source of
      carbohydrate in the diet and the selection patterns of rats were analyzed for 28
      d by a two-choice selection method. Diets provided as a set of two either Zn
      adequate or Zn-deficient diets were changed in position daily. Control Zn
      adequate and Zn-deficient rats both exclusively selected the sucrose diet at days
      1 and 2, after onset of the feeding experiment, and then gradually selected the
      maltose-diet. After changing their preference from sucrose to maltose, the Zn
      adequate control rats selected widely from both the maltose and sucrose diets,
      while the Zn-deficient rats exclusively and continuously selected the maltose
      diet from the two diets over the experimental period. The level of selection of
      sucrose-diet on day 28 had a correlation with the intestinal sucrase activity in
      the control rats. The sum of daily maltose and sucrose diet intake in rats fed a
      Zn-deficient diet showed a characteristic variation with the cyclic period of
      3.6+/-0.2 d. The daily body-weight change of rats fed a Zn-deficient diet was
      well synchronized with their own food intake cycle. The day before changing
      preference from sucrose to maltose in rats fed a Zn-deficient diet represented a
      trough in their own food intake and body-weight cycles. These results suggest
      that one sign of a change in preference from sucrose to maltose in Zn-deficient
      rats is caused by a stage of negative energy balance.

PMID- 19763038
TI  - Long-term oral polyamine intake increases blood polyamine concentrations.
AB  - Although the intracellular de novo synthesis of the polyamines decreases with
      age, there is no similar trend in blood polyamine levels, but rather there is
      wide individual variability. We hypothesized that dietary polyamines attenuate a
      decrease in blood polyamine levels with age and augment the previously observed
      individual variability. The effect of a polyamine rich diet, in both mice and
      humans, on blood polyamine concentrations was examined in this study. Jc1:ICR
      male mice were fed test diets containing 3 different polyamine concentrations.
      Healthy human male volunteers added 50 to 100 g of the polyamine-rich fermented
      soybean product, natto, to their daily intake. After 26 wk, the mean blood
      spermine concentration in mice receiving the test diet with high polyamine
      concentrations was 10.1+/-2.4 micromol/L, while the mean concentrations found in
      mice fed with a diet with normal or low polyamine concentrations were 5.2+/-0.9
      and 4.7+/-0.5 micromol/L, respectively (p<0.05). A mean daily intake of 66.4+/
      3.7 g (range=46.4-89.3 g) of natto for 2 mo by human volunteers increased the
      mean blood spermine concentration by a factor of 1.39 (n=10) (p<0.01), while in
      control volunteers (n=7), asked to exclude polyamine-rich foods from their diet,
      blood spermine concentration remained unchanged. The individual variability of
      blood polyamine levels was enhanced after polyamine intake in mice and, to a
      lesser extent, in humans. The long-term oral intake of enhanced polyamine diets
      increases blood polyamine levels in both mice and humans.

PMID- 19763039
TI  - Sub-chronic effects of s-limonene on brain neurotransmitter levels and behavior
      of rats.
AB  - The present study was designed to gain insight into the effects of s-limonene on
      the brain after 1-wk administration. For this purpose, neurotransmitters such as
      dopamine (DA), serotonin (5-HT), gamma-aminobutyric acid (GABA), glutamic acid
      (Glu) and some of their metabolites (DOPAC and 5-HIAA) were determined by HPLC
      ECD and amino acid analyzer after 1-wk administration of s-limonene of different
      concentrations (0, 5, 25, 50 mg/kg). Significant changes, such as GABA, 5
      hydroxyindoleacetic acid (5-HIAA) and 5-HT, were confirmed. At the same time,
      basal hypothalamic-pituitary-adrenal (HPA) activity after 1-wk administration of
      s-limonene was evaluated by corticosterone. Considering the increment of GABA and
      the changes of other neurotransmitters, anti-stress effects after 1-wk
      administration were observed. The experimental results showed that s-limonene
      could inhibit HPA activity under physical stress and this anti-stress effect of s
      limonene may act through the GABA(A) receptor.

PMID- 19763040
TI  - Effects of dietary docosahexaenoic acid connecting phospholipids on the learning
      ability and fatty acid composition of the brain.
AB  - The effects of dietary docosahexaenoic acid (DHA, C22:6n-3) connecting
      phospholipids on the learning ability and fatty acid composition of the brain
      were investigated in hypercholesterolemic mice. ICR mice were subjected to a very
      low level of n-3 fatty acids through two generations. At 4 wk of age, the F(1)
      generation, n-3 fatty acid deficient male mice were provided with an experimental
      diet containing four kinds of lipids (safflower oil: Saf, DHA connecting
      triacylglycerols: DHA-TG, DHA connecting phospholipids: DHA-PL, soybean
      phospholipids: Soy-PL) for 5 wk. Another group of ICR mice were obtained and fed
      a commercial diet (CE-2, CLEA Japan, Inc.) as a control. The learning and memory
      abilities of the mice were evaluated by the modified avoidance procedure. The
      learning and memory ability level was significantly higher in mice fed the DHA-PL
      diet than in those fed the Saf and Soy-PL diets, and was the same level as the
      control. The DHA levels of phosphatidylethanolamine in the brain were
      significantly higher in the mice fed the two types of DHA-containing diets than
      in those fed the Saf and Soy-PL diets and was not significantly different between
      DHA-TG and DHA-PL. The dimethylacetal levels in the brain were significantly
      higher in the mice fed the DHA-PL diet than in those fed the Saf and DHA-TG
      diets. These results suggest that the dietary DHA connecting phospholipids have
      the effect of improving memory learning, and may be related to the both the DHA
      and plasmalogen levels in the brain.

PMID- 19763041
TI  - Measurement of the rate of myofibrillar protein degradation using the
      arteriovenous difference in plasma 3-methylhistidine concentration of rats.
AB  - There are several methods for measuring the rate of myofibrillar protein
      degradation using 3-methylhistidine (3-MeHis) levels in urine, plasma and
      isolated muscle. However, these methods lack the accuracy of rate measurements.
      Therefore, it is necessary to develop a new method for determining the rate of
      myofibrillar protein degradation. We characterized an arteriovenous difference
      method using 3-MeHis plasma concentration. Rats were fasted overnight and
      subsequently administered leucine (135 mg/100 g BW) or fed a 20% casein diet. The
      rate of myofibrillar protein degradation was calculated by multiplying the
      femoral artery blood flow rate by the arteriovenous difference in 3-MeHis
      concentrations (vein-artery). The blood was collected from the femoral vein and
      abdominal aorta. The release of 3-MeHis from hindlimb muscle was significantly
      suppressed (p<0.05) in rats fed leucine or the 20% casein diet, indicating that
      myofibrillar protein degradation was suppressed. These results suggest that the
      evaluation of the rate of myofibrillar protein degradation using the
      arteriovenous difference method reflects nutritional conditions in a more
      physiological manner.

PMID- 19763042
TI  - The screening method of a bifidogenic dietary fiber extracted from inedible parts
      of vegetables.
AB  - Total dietary fiber (DF) was extracted from the inedible parts of vegetables such
      as peel of taro and Chinese yam, pea pod, broad bean pod, and broad bean testa.
      Effects of these fibers on the growth of bifidobacteria were determined by two
      kinds of experiments: one was to determine the increase of Bifidobacterium longum
      JCM1217 (B. longum) in medium containing DF, the other was an in vitro
      fermentation of the DF by anaerobic slurries of mixed human fecal or rat cecal
      microbiota. Anaerobic culture was carried out for 48 h in both experiments. In
      the pure culture of B. longum, the significant increase of bacterial number was
      observed as compared with 0 h in the medium containing the DF from peel of
      Chinese yam, pea pod and broad bean pod (p<0.05). On the other hand, bacterial
      number was decreased in the medium containing the DF from the peel of taro and
      broad bean testa. We selected the DF from pea pod because of its highest
      bifidogenic property in human fecal microbiota. In the fermentation of DF from
      pea pod by rat cecal microbiota, bifidobacteria and lactobacilli were increased.
      Bacteroidaceae and clostridia were decreased. These results suggested that DF
      from pea pod had possibility as a prebiotic. The bifidogenic property was
      affected by the sugar composition of DF.

PMID- 19763043
TI  - Troglitazone inhibits vascular endothelial growth factor-induced angiogenic
      signaling via suppression of reactive oxygen species production and extracellular
      signal-regulated kinase phosphorylation in endothelial cells.
AB  - Thiazolidinediones, peroxisome proliferators-activated receptor gamma (PPARgamma)
      ligands, have been recognized as a potential therapeutic agents for the treatment
      of pathological neovascularization. In the present study, we examined the
      molecular mechanism by which troglitazone (TROG), a PPARgamma agonist, exerts its
      inhibitory action in vascular endothelial growth factor (VEGF)-induced
      angiogenesis signaling. In an in vitro angiogenesis model using human umbilical
      vein endothelial cells, TROG (20 muM) significantly suppressed VEGF-induced cell
      proliferation and invasion of the cells into the Matrigel basement membrane,
      which was not reversed by treatment with PPAR antagonists, GW9662 (10 muM) and
      bisphenol A diglycidyl ether (10 muM). TROG also blocked VEGF-induced reactive
      oxygen species (ROS) production and its downstream extracellular signal-regulated
      kinase (ERK) phosphorylation, and this inhibitory effect was not reversed by
      GW9662 (10 muM). The antiangiogenic activity of TROG correlated with suppression
      of VEGF-induced matrix metalloproteinase (MMP)-2 and membrane type 1 (MT1)-MMP
      expression. In addition, the effects of TROG on VEGF-induced MMP-2 and MT1-MMP
      expression were comparable to those of the NADPH oxidase inhibitor diphenylene
      iodium (10 muM) and ERK inhibitor PD98056 (10 muM). Furthermore, in an in vivo
      angiogenesis system using a chick chorioallantoic membrane model, TROG dose
      dependently inhibited VEGF-induced angiogenesis, which was similar to the
      inhibitory effect of N-acetylcysteine on VEGF-induced angiogenesis. The results
      suggest that the inhibitory effects of TROG on VEGF-induced angiogenesis were
      mediated through the suppression of VEGF-induced ROS production and ERK
      phosphorylation.

PMID- 19763044
TI  - Oral administration of curcumin suppresses production of matrix metalloproteinase
      (MMP)-1 and MMP-3 to ameliorate collagen-induced arthritis: inhibition of the
      PKCdelta/JNK/c-Jun pathway.
AB  - We investigated whether oral administration of curcumin suppressed type II
      collagen-induced arthritis (CIA) in mice and its effect and mechanism on matrix
      metalloproteinase (MMP)-1 and MMP-3 production in CIA mice, RA fibroblast-like
      synoviocytes (FLS), and chondrocytes. CIA in mice was suppressed by oral
      administration of curcumin in a dose-dependent manner. Macroscopic observations
      were confirmed by histological examinations. Histological changes including
      infiltration of immune cells, synovial hyperplasia, cartilage destruction, and
      bone erosion in the hind paw sections were extensively suppressed by curcumin.
      The histological scores were consistent with clinical arthritis indexes.
      Production of MMP-1 and MMP-3 were inhibited by curcumin in CIA hind paw sections
      and tumor necrosis factor (TNF)-alpha-stimulated FLS and chondrocytes in a dose
      dependent manner. As for the mechanism, curcumin inhibited activating
      phosphorylation of protein kinase Cdelta (PKCdelta) in CIA, FLS, and
      chondrocytes. Curcumin also suppressed the JNK and c-Jun activation in those
      cells. This study suggests that the suppression of MMP-1 and MMP-3 production by
      curcumin in CIA is mediated through the inhibition of PKCdelta and the JNK/c-Jun
      signaling pathway.

PMID- 19763046
TI  - Possible involvement of mitochondrial energy-producing ability in the development
      of right ventricular failure in monocrotaline-induced pulmonary hypertensive
      rats.
AB  - The present study was undertaken to explore the possible involvement of
      alterations in the mitochondrial energy-producing ability in the development of
      the right ventricular failure in monocrotaline-administered rats. The rats at the
      6th week after subcutaneous injection of 60 mg/kg monocrotaline revealed marked
      myocardial hypertrophy and fibrosis, that is, severe cardiac remodeling. The time
      course study on the cardiac hemodynamics of the monocrotaline-administered rat by
      the cannula and echocardiographic methods showed a reduction in cardiac double
      product, a decrease in cardiac output index, and an increase in the right
      ventricular Tei index, suggesting that the right ventricular failure was induced
      at the 6th week after monocrotaline administration in rats. The mitochondrial
      oxygen consumption rate of the right ventricular muscle isolated from the
      monocrotaline-administered animal was decreased, which was associated with a
      reduction in myocardial high-energy phosphates. Furthermore, the decrease in
      mitochondrial oxygen consumption rate was inversely related to the increase in
      the right ventricular Tei index of the monocrotaline-administered rats. These
      results suggest that impairment of the mitochondrial energy-producing ability is
      involved in the development of the right ventricular failure in monocrotaline
      induced pulmonary hypertensive rats.

PMID- 19763045
TI  - Aralia cordata protects against amyloid beta protein (25-35)-induced
      neurotoxicity in cultured neurons and has antidementia activities in mice.
AB  - The present study investigated an ethanol extract of the aerial part of Aralia
      cordata Thunb. (Araliaceae) for possible neuroprotective effects on neurotoxicity
      induced by amyloid beta (Abeta) protein (25 - 35) in cultured rat cortical
      neurons and antidementia activity in mice. Exposure of cultured cortical neurons
      to 10 muM Abeta(25 - 35) for 36 h induced neuronal apoptotic death. At 1 - 10
      mug/ml, A. cordata inhibited neuronal death, elevation of intracellular calcium
      ([Ca(2+)](i)), glutamate release into the medium, and generation of reactive
      oxygen species (ROS) induced by Abeta(25-35) in primary cultures of rat cortical
      neurons. Memory loss induced by intracerebroventricular injection of ICR mice
      with 15 nmol Abeta(25-35) was inhibited by chronic treatment with A. cordata (50
      and 100 mg/kg, p.o. for 7 days) as measured by a passive avoidance test, and
      corresponding reductions were observed in brain cholinesterase activity and
      neuronal death measured histologically in the hippocampal region. Oleanolic acid
      isolated from A. cordata also inhibited neuronal death, elevation of [Ca(2+)](i),
      glutamate release, and generation of ROS induced by Abeta(25-35) in cultured rat
      cortical neurons, suggesting that the neuroprotective effect of A. cordata may
      be, at least in part, attributable to this compound. From these results, we
      suggest that the antidementia effect of A. cordata is due to its neuroprotective
      effect against Abeta(25-35)-induced neurotoxicity and that A. cordata may have a
      therapeutic role in preventing the progression of Alzheimer's disease.

PMID- 19763047
TI  - Seasonal trivalent influenza vaccine for 2009-2010.

PMID- 19763048
TI  - Resveratrol.

PMID- 19763050
TI  - The reality and the reliability of esophageal cancer treatment: which will you
      choose for yourself?

PMID- 19763049
TI  - Artemether-lumefantrine (Coartem) for treatment of malaria.

PMID- 19763052
TI  - An accurate diagnosis of Noguchi classification is possible after the
      modification of preoperative biopsy-induced fibrosis.
AB  - PURPOSE: After computed-tomography-guided needle biopsy (CTNB), the lung may
      undergo iatrogenic fibrosis (post-CTNB fibrosis), which can be misdiagnosed as
      tumor-induced fibrosis. The purpose of the study was to examine if an accurate
      evaluation of pulmonary adenocarcinoma can be made using the Noguchi
      classification (type A or B vs. type C), even after CTNB. MATERIALS AND METHODS:
      The subjects were 71 patients with primary pulmonary adenocarcinoma of 20 mm or
      less that had been resected surgically after CTNB. Twenty-four patients who did
      not undergo a preoperative biopsy served as controls. Resected specimens were
      stained with hematoxylin-eosin (HE) and elastic-fiber staining for a precise
      observation of fibrosis. RESULTS: The period from CTNB to surgery ranged from 12
      to 153 days. Post-CTNB fibrosis consisted primarily of collagen fibers with a few
      thin elastic fibers observed only with high magnification, which was able to
      distinguish post-CTNB fibrosis in 39 of 48 patients (81.3%) with
      bronchioloalveolar carcinoma (BAC) lesions (types A/B/C) and in 6 of 23 patients
      (26.1%) without BAC lesions (types D/E/F/E + F), showing a significant difference
      (p <0.0001). In the control group, no lesions that resembled post-CTNB fibrosis
      were observed. CONCLUSION: An evaluation of pulmonary adenocarcinoma by Noguchi
      classification can be accurately performed even after CTNB.

PMID- 19763053
TI  - Reconstructive surgery for an akinetic anterior ventricular wall in ischemic
      cardiomyopathy.
AB  - BACKGROUND: The purpose of this prospective study is to analyze the postoperative
      outcome after only left ventricular reconstruction (LVR) versus LVR combined with
      coronary artery bypass grafting (CABG) and/or mitral valve (MV) procedure in
      ischemic cardiomyopathy (ICM) as a result of an akinetic anterior ventricular
      wall. METHODS AND RESULTS: Nineteen patients underwent only LVR, and 37 underwent
      a concomitant LVR procedure. In both groups, New York Heart Association (NYHA)
      classification improved significantly from 3.5 +/- 0.6 to 2.2 +/- 0.5 (LVR group)
      and 3.4 +/- 0.7 to 2.5 +/- 0.5 (combined LVR group). Ejection fraction improved
      significantly from 25.1 +/- 3.2 to 35.3 +/- 4.5% in the LVR group and 28.1 +/-
      2.2 to 37.6 +/- 5.5% in the combined LVR group. Cardiac index improved
      significantly from 1.8 +/- 0.6 to 2.3 +/- 0.5 l/min/m2 in the LVR group and 1.6
      +/- 0.4 to 2.2 +/- 0.6 l/min/m2 in the combined LVR group. An additional
      concomitant procedure increased the mortality rate only slightly. The overall 1-
      and 5-year actuarial survival rates were 90% and 75% in the LVR group and 80% and
      70% in the combined LVR group. CONCLUSIONS: The LVR for akinetic ventricular wall
      shows very satisfactory early and long-term results. The LVR, with or without
      concomitant procedures, has considerable benefits for operative therapy.

PMID- 19763054
TI  - The efficacy of intravenous milrinone in left ventricular restoration.
AB  - PURPOSE: The aim of this study was to clarify the efficacy of intravenous
      milrinone in postoperative care for patients following left ventricular (LV)
      restoration (LVR). METHODS: Fourteen patients who had ischemic cardiomyopathy
      with an LV ejection fraction (LVEF) of less than 0.30 and an LV end-systolic
      volume index of more than 100 ml/m2 underwent coronary artery bypass grafting and
      concomitant LVR. The patients received perioperative management with continuous
      infusions of 0.5 microg/kg/min milrinone that were started at the induction of a
      cardiopulmonary bypass (CPB). The perioperative course and outcome of these
      patients were retrospectively compared with those of matched LVR patients (n =
      14) without milrinone administration during perioperative management. RESULTS:
      The preoperative LV end-diastolic pressure (26.3 mmHg vs. 15.4 mmHg) and early
      diastolic filling velocity/atrial filling velocity ratio (4.1 vs. 2.1) in the
      milrinone patients were significantly worse than those in the control. Even
      though the preoperative LV function in each patient demonstrated to be extremely
      poor, the perioperative hemodynamic variables were stable. The administered doses
      of dobutamine (4.01 vs. 5.81 microg/kg/min) and epinephrine (0.017 vs. 0.038
      microg/kg/min) at the end of CPB were significantly lower in the milrinone
      patients compared to control. CONCLUSION: In those patients who underwent LVR
      because of ischemic cardiomyopathy, the administration of milrinone achieved safe
      perioperative management for stable hemodynamics and reduced the postoperative
      doses of dobutamine and epinephrine.

PMID- 19763055
TI  - Early tracheal extubation after on-pump coronary artery bypass grafting.
AB  - OBJECTIVE: A fast-track recovery in cardiac surgery yields many benefits, and
      early tracheal extubation is important as the first step. The purpose of this
      study is to evaluate the status of early tracheal extubation after on-pump
      coronary artery bypass grafting (CABG) and to find key factors for successful
      early tracheal extubation. METHODS: From September 1996 to February 2005,
      isolated on-pump CABG was performed on 485 patients, and an early tracheal
      extubation protocol was employed on all. It was defined as tracheal extubation
      within 6 hr of arrival in the intensive care unit (ICU). RESULTS: An early
      tracheal extubation was successful on 450 patients (92.5%). Reintubation was
      necessary in 5 (1.1%) because of a resternotomy for bleeding in 3 and ventricular
      arrhythmia in 2. Mechanical ventilation exceeding 24 hours was required in 7
      patients (1.4%) because of heart failure in 4 and respiratory failure in 3.
      Significant factors of successful early tracheal extubation were the European
      System for Cardiac Operative Risk Evaluation (P <0.05), the number of diseased
      arteries (P <0.01), ejection fraction (P <0.05), operation time (P <0.01), blood
      transfusion in ICU (P <0.05), and drainage in the first 12 hr (P <0.05).
      CONCLUSIONS: Early tracheal extubation can be successfully performed in most
      patients receiving on-pump CABG. The management of higher-risk patients and
      efforts to reduce operation time and blood loss are keys to success for early
      tracheal extubation.

PMID- 19763056
TI  - Early postoperative recovery by chronic dialysis patients after coronary artery
      bypass grafting.
AB  - OBJECTIVE: A faster start at rehabilitation has been a great benefit in reducing
      complications and costs after coronary artery bypass grafting (CABG). We studied
      early postoperative recovery from CABG in dialysis patients. METHODS: From
      January 2001 to May 2006, a total of 401 patients underwent isolated CABG at our
      institution. We retrospectively studied 348 consecutive elective cases, which
      were divided into two groups; 18 with dialysis (group D) and 330 without dialysis
      (group N), with respect to having meals, standing, and walking. RESULTS: An
      analysis of patient demographics revealed significant differences in gender,
      comorbidity of old cerebral infarction, anemia, and water balance during
      operation (P <0.05). Operative and in-hospital mortalities were 0% in group D.
      The percentages of the patients who were eating meals, standing, or walking on
      postoperative day (POD) 1 in group D were 88.9%, 66.6%, and 27.8%, respectively.
      In group N, these percentages were significantly higher: 96.1%, 85.5%, and 75.8%.
      But by POD 2, these values became similar. We considered that the delay of
      rehabilitation in group D was mainly due to hemodialysis on POD 1. CONCLUSION:
      Early postoperative recovery from elective isolated CABG in dialysis patients
      delayed a day against nondialysis patients. The delay was considered a result of
      the inevitable dialysis on POD 1.

PMID- 19763051
TI  - A translational approach to lung cancer research: From EGFRs to Wnt and cancer
      stem cells.
AB  - Lung cancer remains the main cause of all cancer deaths in the United States. The
      prognosis for non-small cell lung cancer, despite advances in current therapies,
      is disappointing. Fortunately, we are steadily gaining significant insights into
      the heterogeneous molecular pathogenesis of lung cancer, which seems to occur in
      a stepwise manner, mainly secondary to tobacco smoking. With the emerging power
      of gene expression signatures for individual lung tumors and with the advancing
      field of stem cell biology and the paradigm of cancer stem cells, we are most
      certainly paving the way to developing novel tools for the early detection,
      chemoprevention, and treatment of these vastly morbid pathologies with enormous
      global burden. We will explore some of these issues and highlight how we are
      starting to translate them into clinically relevant tools for lung cancer
      patients.

PMID- 19763057
TI  - Primary pulmonary teratoma: Report of a case and the proposition of
      "bronchotrichosis" as a new term.
AB  - Primary pulmonary teratoma is a very rare disease. Most follow a benign course
      and are incidental findings during routine chest X-rays. Hair found in sputum or
      in bronchus detected during bronchoscopy is also a rare condition and is usually
      caused by mediastinal teratoma. This case report is of a 36-year-old man who
      presented with halitosis. A fiber-optic bronchoscopy revealed coarse hair
      originated from the right upper lobe. The patient was successfully treated by
      right upper lobectomy, and pathology confirmed primary pulmonary teratoma. We
      recommend that "bronchotrichosis" could be used as a new term for such a sign.

PMID- 19763058
TI  - Subpleural intrapulmonary lymph node metastasis from colorectal cancer.
AB  - A 67-year-old male was admitted to our hospital because of pulmonary metastasis
      from colo-rectal cancer. Chest computed tomography revealed three tumor shadows
      just under the pleura. Because the tumors were adjacent to each other, we
      performed an en bloc pulmonary resection. Pathologically, two of the tumors were
      diagnosed as pulmonary metastases; the remaining tumor, however, was diagnosed as
      a subpleural intrapulmonary lymph node (IPLN) metastasis. Metastasis to the IPLN
      is rare, but when the IPLN is located adjacent to a pulmonary metastasis, as
      observed in this case, it may be possible.

PMID- 19763059
TI  - Successful bleeding control by a combined conventional surgical approach and
      video-assisted surgery: a case report.
AB  - The use of central venous catheters (CVCs) nowadays is a routine practice in the
      treatment of severely acute-diseased children. However, the procedure still
      carries a risk of morbidity, and severe complications are reported. When
      respiratory and/or hemodynamic instability develop after the procedure, prompt
      patient evaluation to exclude iatrogenic damage is mandatory, regardless of the
      primary patient condition. If a vascular injury related to CVC placement
      procedure is detected, the availability of an interventional radiologist and/or
      any surgical facilities plays an important role in the management of this life
      threatening complication. We report the case of a 12-year-old boy hospitalized in
      the Pediatric Intensive Care Unit of our hospital for a severe motorveicle
      accident, who, about 30 minutes from the percutaneous CVC placement, developed
      tachycardia, hypoxemia, and hypotension. A chest X-ray confirmed the right
      positioning of the catheter, the presence also of a large left hemothorax.
      Interventional radiology took place, but it failed to stop the bleeding. Urgent
      anterolateral thoracotomy was performed while the patient was kept in a supine
      position because of a cervical spine luxation. During surgery, bleeding was found
      coming from the thoracic dome and because of a tear next to the left subclavian
      artery. Access to that area was technically difficult; after blood and clots were
      removed, multiple attempts to obtain the hemostasis failed, and definitive
      control of the hemorrhage was achieved only by video-assisted thoracic surgery
      (VATS). The postoperative period was uneventful. In this study, the authors
      discuss the management of this kind of complication and the value of a combined
      surgical approach (conventional, with a minimal access surgery procedure such as
      VATS) in the treatment of thoracic vascular injuries related to the insertion of
      a percutaneous CVC. To the best of our experience, this is the first time in
      which this combination of procedures has been reported in the literature.

PMID- 19763060
TI  - A patient in whom survival was achieved by acute-stage surgery for infective
      endocarditis complicated by a cerebral hemorrhage.
AB  - We report a patient who underwent mitral valve replacement despite acute-stage
      cerebral hemorrhage related to a complication of infective endocarditis (IE) and
      rupture of intracerebral mycotic aneurysm, achieving survival. The patient was a
      24-year-old female. She consulted our hospital because of a fever and was
      diagnosed with IE and a cerebral hemorrhage. A blood culture test on admission
      revealed methicillin-sensitive Staphylococcus aureus. Transthoracic
      echocardiography revealed giant vegetation in the left atrium. Besides the
      management of an acute-stage cerebral hemorrhage, medical therapy for IE was
      performed. However, a severe infection was refractory, and mitral-regurgitation
      related heart failure deteriorated. Despite acute-stage cerebral hemorrhage,
      mitral valve replacement was performed 10 days after admission because advanced
      disseminated intravascular coagulation syndrome made conservative management
      difficult. After surgery, neither exacerbation of cerebral symptoms nor recurrent
      IE was noted, and the patient was discharged.

PMID- 19763061
TI  - Palliative stent-graft insertion followed by an allograft replacement for an
      infected and ruptured aortic aneurysm.
AB  - We report a surgical case of infected thoracic aortic aneurysm. Before arrival of
      the cryopreserved aortic allograft, the patient had hemoptysis resulting from
      aneurysm rupture. Therefore endovascular stent grafting was urgently performed
      three days prior to in situ allograft implantation. Palliative stent grafting
      prevented circulatory collapse and stabilized the patient until successful
      allograft implantation.

PMID- 19763062
TI  - Hemostatic effectiveness of a new application method for fibrin glue, the "rub
      and-spray method", in emergency aortic surgery for acute aortic dissection.
AB  - PURPOSE: This study was performed to evaluate the clinical hemostatic
      effectiveness of a new application method for fibrin glue, the rub-and-spray
      method, in aortic surgery. METHODS: Twenty consecutive patients undergoing
      emergency ascending aorta or ascending-hemiarch replacement for Stanford type A
      acute aortic dissection were prospectively randomized into 2 groups, one with the
      rub-and-spray method (group G, 10 patients) and one without fibrin glue (group C,
      10 patients). The rub-and-spray method consists of using a finger to rub the
      fibrinogen solution over needle holes, then spraying the fibrinogen solution and
      the thrombin solution simultaneously over the anastomosis, using an application
      nozzle. The number of bleeding needle holes at the proximal and distal
      anastomoses just after reperfusion, the hemostatic period (time from
      administration of protamine sulfate until closure of the pericardium), and the
      amounts of blood losses during this hemostatic period were measured. RESULTS: The
      values in group G and group C were as follows: proximal needle holes (26.8 +/-
      1.5, 26.4 +/- 2.4, p = 0.466); proximal bleeding needle holes (0.2 +/- 0.4, 19.3
      +/- 3.5, p <0.001); distal needle holes (28.7 +/- 2.5, 27.8 +/- 4.4, p = 0.675);
      distal bleeding needle holes (1.3 +/- 1.2, 19.9 +/- 5.0, p <0.001); estimated
      bleeding proportion of the proximal needle holes (0.7 +/- 1.6%, 73.8 +/- 16.0%, p
      <0.001); estimated bleeding proportion of the distal needle holes (4.4 +/- 3.7%,
      71.9 +/- 15.7%, p <0.001); estimated median hemostatic period (41.5 min [32-49],
      51 min [44-89], p = 0.036); amounts of blood losses during this hemostatic period
      (99 +/- 76 ml, 257 +/- 163 ml, p = 0.016). The number of bleeding needle holes,
      the bleeding proportion of the proximal and distal needle holes, the hemostatic
      period, and the amounts of bleeding during this hemostatic period were
      significantly less in group G. CONCLUSION: This new application method for fibrin
      glue, the rub-and-spray method, revealed significant hemostatic effectiveness,
      even in hemostatically difficult surgery of acute aortic dissection that requires
      systemic heparinization and prolonged cardiopulmonary bypass with deep
      hypothermia.

PMID- 19763064
TI  - The role of stress echocardiography and competing technologies for the diagnostic
      and prognostic assessment of coronary artery disease.
AB  - Coronary artery disease remains the leading cause of death in adults in the
      United States. Non-invasive cardiac imaging is now central to the diagnosis and
      management of patients with known or suspected coronary disease. The generally
      accepted indications for stress testing include confirming a diagnosis of
      coronary disease, assessing prognosis, preoperative risk stratification, and
      evaluation of medical therapy. Stress echocardiography and single photon computed
      tomography are well-established non-invasive techniques for all the previously
      mentioned indications. These modalities provide a relatively high sensitivity and
      specificity along with an incremental value over clinical risk factors. Cardiac
      magnetic resonance imaging (CMRI) and multislice computed tomography are new
      imaging tools in the evaluation of patients with coronary disease. CMRI offers a
      comprehensive cardiac evaluation which includes wall motion analysis, myocardial
      tissue morphology, rest and stress first pass myocardial perfusion as well as
      systolic ventricular function. It is also considered a first line technique for
      the diagnosis of certain structural heart disease and chamber volume
      quantification. Cardiac computed tomography allows non-invasive anatomic imaging
      of the coronary tree. It has a high clinical utility especially in select
      intermediate risk patient population. Available tests all have advantages and
      drawbacks and none can be considered suitable for all patients. The choice of the
      imaging method should be tailored to each person based on the clinical judgment
      of the a priori risk of cardiac event, clinical history, and risk factors
      profile.

PMID- 19763063
TI  - Acid-base management and temperature control during hypothermic circulatory
      arrest.

PMID- 19763066
TI  - Advanced applications of 3-dimensional echocardiography.
AB  - Over the last few decades, advancements in ultrasound, electronic and computing
      technologies have permitted current second generation 3-dimensional (3D)
      echocardiography to display on-line 3D rendered images of the heart. Since
      various studies demonstrated its superiority over 2-dimensional echocardiography,
      there is growing enthusiasm to embrace this new 3D echocardiographic technology.
      With its increasing widespread clinical availability, 3D echocardiography is
      getting closer to routine clinical use. However, as with any new emerging
      technologies, clinical applications of 3D echocardiography should be based on
      current evidence. This review will focus on the evidence from clinical studies
      that form the scientific basis for the advanced applications of 3D
      echocardiography, from cardiac chamber volume assessments, left ventricular
      dyssynchrony assessments, quantifications of valvular abnormalities, to the role
      of 3D echocardiography during cardiac interventions.

PMID- 19763065
TI  - Role of echocardiography in the assessment of adolescents and adults with
      congenital heart disease.
AB  - Adolescent and adults with congenital heart disease (CHD) represent a special
      group of individuals. They often require regular assessment of their cardiac
      anatomy and functional hemodynamics. Most children with repaired CHD surviving to
      adulthood are either corrected or fully repaired and may not require long term
      follow-up. However, there are is a significant number of grown up children with
      residual abnormality or palliated defects, in whom full correction was not
      possible. Some of them are likely to present with complications and need repeated
      evaluation. Others may require improvement or stabilisation of their hemodynamics
      during stressful period like pregnancy or non-cardiac surgery. These conditions
      include single ventricle repair, repaired tetralogy, Mustard or Sennings
      operation for transposition of great arteries, aortic arch abnormalities,
      postatrioventricular septal defect (AVSD) repair, bicuspid aortic valve, Ebstein
      anomaly and unoperated congenital heart disease leading to Eisenmenger syndrome.
      The focus of this discussion will be mainly on this subset.

PMID- 19763067
TI  - Controversies in echocardiography: 2D vs 3D vs 4D.
AB  - In the latest years several manuscripts have showed some new possible advantages
      of the three-dimensional (3D) echocardiography in daily practice. 3D
      echocardiography allows imaging and analysis of cardiovascular structures as they
      move in time and space, thus creating possibility for creation of 4D datasets (3D
      and real-time). Real-time three-dimensional echocardiography (RT3DE) is a major
      innovation in the history of cardiovascular ultrasound. Advances in computer and
      transducer technologies, especially the fully-sampled matrix array transducer,
      have permitted real-time 3D image acquisition and display. The aim of this
      manuscript is to give a brief review of the development of the 3D
      echocardiography and of comparison of two-dimensional echocardiography versus 3D
      echocardiography and RT3DE.

PMID- 19763068
TI  - Echocardiography in the assessment of heart failure.
AB  - Echocardiography with Doppler is the most commonly performed non-invasive cardiac
      imaging test in patients with suspected or documented heart failure (HF), and
      plays a pivotal role in their assessment and management. Two- and three
      dimensional echocardiography are commonly used to quantitatively assess cardiac
      volumes, left ventricular ejection fraction (LVEF), stroke volume and cardiac
      output. Resting and stress echocardiography the latter with exercise or
      pharmacologic stress play a fundamental role in distinguishing ischemic from non
      ischemic etiology of HF and in demonstrating myocardial viability. Echocar
      diography with comprehensive spectral and color Doppler can accurately determine
      if valve disease plays a primary or secondary role in HF etiology. Diastolic
      heart failure (DHF) also termed HF with a preserved LVEF is readily identified by
      echocardiography with Doppler, and can accurately estimated LV filling pressures
      and pulmonary artery pressures. The right ventricle can also be readily assessed
      by echocardiography, with newer techniques such as three-dimensional, tissue
      Doppler and speckle strain imaging aiding its assessment. Echocardiography is
      also commonly used to identify candidates for implantable cardiac defibrillator
      and cardiac resynchronization therapies. Three-dimensional echocardiography now
      easily preformed with single-beat full volume capture promises to further refine
      HF diagnosis. Finally, speckle-based strain and strain rate, and three
      dimensional speckle imaging, are more novel techniques that can shed light on
      detailed myocardial mechanics in patients with depressed or preserved LVEF.

PMID- 19763069
TI  - Diagnostic value of transesophageal echocardiography in Libman-Sacks
      endocarditis.
AB  - Libman-Sacks endocarditis is the most common cardiac manifestation in patients
      with systemic lupus erythematosus (SLE) and primary antiphospholipid syndrome
      (PAPS); it is characterized by Libman-Sacks vegetations, valve thickening or
      fibrosis, valve regurgitation, and rarely valve stenosis. It is most commonly
      clinically manifested with cardioembolism (predominantly to the brain),
      uncommonly with symptomatic severe valve regurgitation, or rarely with over
      imposed infective endocarditis. These three clinical syndromes are associated
      with a five to eight times higher morbidity and mortality than in a general
      population. Libman-Sacks endocarditis is infrequently detected by the history and
      cardiovascular physical examination; it is detected by transthoracic
      echocardiography (TTE) in 30-40% as compared to 60-80% of patients by
      transesophageal echocardiography (TEE). Also, TTE as compared to TEE has low
      sensitivity (63% overall, 11% for valve vegetations), low specificity (58%), low
      negative predictive value (40%), and a moderate positive predictive value (78%)
      for the detection of Libman-Sacks endocarditis. In addition, TEE has played a
      major role in our current understanding of the specific characteristics,
      evolution, assessment of prognosis, and defining the need and response to medical
      or surgical therapy of Libman-Sacks endocarditis. Therefore, an increased
      awareness of the potential clinical complications of Libman-Sacks endocarditis
      and application of echocardiography, especially of TEE, may lead to an earlier
      and accurate diagnosis, guidance of therapy, prevention of complications,
      decreased rate of progression of the disease, and consequently to an event free
      survival of patients with SLE or PAPS.

PMID- 19763070
TI  - An update on contrast echocardiography.
AB  - Ultrasound contrast agents, used with contrast-specific imaging techniques, have
      an established role for diagnostic cardiovascular imaging in the echocardiography
      laboratory. The advent of tissue harmonic imaging, albeit a significant
      advancement in ultrasound technology, still fail to produce diagnostically useful
      images in a significant proportion of patients. This therefore, often leads to
      inaccurate assessment of left ventricular function, neccesitating the use of
      other more laborious and expensive imaging techniques purely for diagnostic
      purposes. Historically, contrast agents have not been an integral component of
      the echocardiography imaging laboratory. However the need for a more robust
      method for the assessment of left ventricular function facilitated the
      developement of a unique class of contrast agents composed of microbubbles, which
      together with ultrasound, produce opacification of the left ventricular cavity,
      thus enabling accurate quantification of its function. The use of these contrast
      agents have now gone beyond the assessment of wall motion and function to the
      assessment of myocardial perfusion. Myocardial contrast echocardiography has
      enabled the assessment of cardiac anatomy, function and perfusion, all in one
      sitting, by the bedside. Contrast ultrasound imaging has now been applied to even
      newer techniques such as real-time three-dimensional echocardiography and is also
      showing promise in the assessment of carotid ultrasound for intima-media
      thickness. Contrast agents therefore have a significant role in cardiovascular
      diagnostics and its use can only improve patient care.

PMID- 19763071
TI  - Cardiac CT in 2009.
AB  - Multislice computed tomography is an emerging diagnostic modality in cardiology
      practice. Within the last decade a rapid technical evolution from 4-slice
      scanners to 64-slice and meanwhile 320-slice scanners which faster gantry
      rotation time has taken place. These advances as well as improved post-processing
      tools account for a stabilization of image quality and allow assessing cardiac
      structures with high spatial and temporal resolution. Moreover, dedicated
      acquisition techniques have been employed to reduce radiation exposure to a
      minimum. Today cardiac computed tomography is not only able to depict the
      coronary arteries, but to get reliable information about cardiac function and
      cardiac structure. This review focuses on present clinical indications and future
      application of multi-slice computed tomography in clinical cardiology.

PMID- 19763072
TI  - Cardiac magnetic resonance imaging for myocarditis and nonischemic
      cardiomyopathies.
AB  - Cardiovascular magnetic resonance (CMR) is the gold standard for quantification
      of ventricular size, mass and function. Moreover, CMR can differentiate transient
      and permanent tissue damage. Therefore CMR is clinically useful to differentiate
      acute myocarditis from infarction. Various CMR markers for acute myocardial
      inflammation are reviewed. Moreover CMR can differentiate tissue changes in
      various nonischemic cardiomyopathies. This has a major clinical impact for
      diagnosis and risk stratification in these patients. Serial monitoring is
      feasible due to high reproducibility and the lack of radiation. The strengths and
      pitfalls in CMR imaging of nonischemic cardiomyopathies are reviewed in detail
      including an overview of the current literature.

PMID- 19763073
TI  - Valvular regurgitation: does cardiovascular magnetic resonance provide additional
      information compared to echocardiography?
AB  - Surgical intervention for chronic aortic or mitral regurgitation in asymptomatic
      individuals is recommended on the basis of regurgitant severity and the
      hemodynamic consequences on the left ventricle (LV). Echocardiography is the
      standard tool in clinical practice for evaluation of adults with chronic
      regurgitation. Regurgitant volume (RV) and fraction (RF) can be determined as the
      difference between stroke volumes measured at two intracardiac sites: antegrade
      flow across the regurgitant valve compared to antegrade flow across a normal
      valve. Alternatively, these severity measures can be determined by imaging the
      proximal flow convergence. Regurgitant orifice area also can be determined.
      However, limitations do exist with echocardiography due to poor image quality,
      variability in measuring flow diameters and foreshortened views of the ventricle.
      Cardiac magnetic resonance (CMR) imaging is a promising modality which can also
      measure regurgitant severity and may provide additional information about LV size
      and function. Q-flow methods allow measurement of flow velocity and instantaneous
      volume flow rates in the aorta or pulmonary artery; this data can be integrated
      over the cardiac cycle to determine RV and RF. CMR also allows accurate
      measurement of left and right ventricular volumes; the difference in stroke
      volume between the two ventricles is regurgitant volume. The role of CMR in
      clinical management of adults with valve regurgitation merits further study.
      Currently, we find CMR helpful when regurgitant severity is indeterminant on
      echocardiography (particularly if LV dysfunction is present), when more accurate
      measures of LV function are needed and when aortic dilation is present.

PMID- 19763074
TI  - Nonfatal scald-related burns among adults aged >/=65 years--United States, 2001
      2006.
AB  - Scalds, which are burns attributed to hot liquids or steam, account for 33%-58%
      of all patients hospitalized for burns in the United States. Adults aged >/=65
      years have a worse prognosis than younger patients after scald burns because of
      age-related factors and comorbid medical conditions, and they are subject to more
      extensive medical treatment than younger adults. To estimate the number of
      emergency department (ED) visits for nonfatal scald burns among U.S. adults aged
      >/=65 years and describe their characteristics, CDC analyzed ED visit data from
      the National Electronic Injury Surveillance System All Injury Program (NEISS-AIP)
      for 2001-2006. This report summarizes the results, which indicated that adults
      aged =65 years made an estimated 51,700 initial visits to EDs for nonfatal scald
      burns during 2001-2006, for an average of 8,620 visits per year and an estimated
      average annual rate of 23.8 visits per 100,000 population. Two thirds of visits
      were made by women. Most (76%) of the nonfatal scald injuries occurred at home;
      42% were associated with hot food and 30% with hot water or steam. The findings
      in this report highlight the need for effective scald-prevention programs
      targeted to older persons.

PMID- 19763075
TI  - National, state, and local area vaccination coverage among adolescents aged 13-17
      years--United States, 2008.
AB  - In recent years, the Advisory Committee on Immunization Practices (ACIP) has
      recommended three newly licensed vaccines: meningococcal conjugate vaccine (MCV4;
      1 dose); tetanus, diphtheria, acellular pertussis vaccine (Tdap; 1 dose); and
      (for girls) quadrivalent human papillomavirus vaccine (HPV4; 3 doses). ACIP also
      recommends that adolescents receive recommended vaccinations that were missed
      during childhood: measles, mumps, rubella vaccine (MMR; 2 doses); hepatitis B
      vaccine (HepB; 3 doses); and varicella vaccine (VAR; 2 doses). Since 2006, CDC
      has conducted the National Immunization Survey-Teen (NIS-Teen) to estimate
      vaccination coverage from a national sample of adolescents aged 13-17 years. This
      report summarizes results from the 2008 NIS-Teen and, for the first time,
      includes estimates for each of the 50 states and selected local areas.
      Nationally, vaccination coverage for the three most recently recommended
      adolescent vaccinations and one childhood vaccination increased from 2007 to
      2008: MCV4 (from 32.4% to 41.8%), Tdap (from 30.4% to 40.8%), >/=1 dose of HPV4
      (from 25.1% to 37.2%), and >/=2 doses of VAR among those without disease history
      (from 18.8% to 34.1%). However, substantial variability in vaccination coverage
      was observed in 2008 among state and local areas and by race/ethnicity and
      poverty status. For the first time, the Healthy People 2010 target of 90%
      coverage among adolescents aged 13-15 years was met for MMR and HepB. Public
      health agencies should continue annual monitoring of adolescent vaccination
      coverage levels to identify trends and differences by geographic area,
      race/ethnicity, and poverty status.

PMID- 19763076
TI  - Update on vaccine-derived polioviruses--worldwide, January 2008-June 2009.
AB  - In 1988, the World Health Assembly resolved to eradicate poliomyelitis worldwide.
      Subsequently, the Global Polio Eradication Initiative of the World Health
      Organization (WHO) reduced the global incidence of polio associated with wild
      polioviruses (WPVs) from an estimated 350,000 cases in 125 countries in 1988 to
      1,651 reported cases in 2008 and reduced the number of countries that have never
      interrupted WPV transmission to four (Afghanistan, India, Nigeria, and Pakistan).
      Under current WHO plans, when the goal of eradicating all WPV transmission is
      attained, oral poliovirus vaccine (OPV) use worldwide eventually will be
      discontinued. However, because vaccine-derived polioviruses (VDPVs) can produce
      polio outbreaks in areas with low rates of Sabin OPV coverage and can replicate
      for years in immunodeficient persons, enhanced strategies are needed to limit
      emergence of VDPVs. This report updates previous summaries and describes VDPVs
      detected worldwide during January 2008-June 2009. During this period, 1) two new
      outbreaks of circulating VDPVs (cVDPVs) (accounting for 4-20 cases) were
      identified in the Democratic Republic of Congo and Ethiopia; 2) a previously
      identified outbreak in Nigeria ultimately resulted in a cumulative total of 292
      cases; 3) two newly identified paralyzed immunodeficient persons in Argentina and
      the United States were found to excrete VDPVs; and 4) isolated VDPVs were found
      among persons and environmental samples in 11 countries. All countries need to
      maintain 1) high rates of poliovirus vaccination coverage to prevent VDPV spread
      and 2) sensitive poliovirus surveillance to detect VDPVs.

PMID- 19763077
TI  - Updated recommendations from the Advisory Committee on Immunization Practices
      (ACIP) for use of hepatitis A vaccine in close contacts of newly arriving
      international adoptees.
AB  - On February 25, 2009, the Advisory Committee on Immunization Practices (ACIP)
      recommended routine hepatitis A vaccination for household members and other close
      personal contacts (e.g., regular babysitters) of adopted children newly arriving
      from countries with high or intermediate hepatitis A endemicity. This new
      recommendation complements previous ACIP recommendations for hepatitis A
      vaccination for persons traveling from the United States to countries with high
      or intermediate hepatitis A endemicity (including persons with travel related to
      international adoption), and postexposure prophylaxis for contacts of persons
      with hepatitis A. This report introduces the new recommendation and outlines the
      underlying epidemiologic and programmatic rationale.

PMID- 19763078
TI  - Licensure of a Haemophilus influenzae type b (Hib) vaccine (Hiberix) and updated
      recommendations for use of Hib vaccine.
AB  - On August 19, 2009, the Food and Drug Administration (FDA) licensed Hiberix
      (GlaxoSmithKline Biologicals, Rixensart, Belgium), a Haemophilus influenzae type
      b (Hib) conjugate vaccine composed of H. influenzae type b capsular
      polysaccharide (polyribosyl-ribitol-phosphate [PRP]) conjugated to inactivated
      tetanus toxoid (PRP-T). Hiberix is licensed for use as the booster (final) dose
      of the Hib vaccine series for children aged 15 months through 4 years (before the
      5th birthday) who have received previously the primary series of Hib vaccination
      (consisting of 2 or 3 doses, depending on the formulation). The Advisory
      Committee on Immunization Practices (ACIP) recommends Hib booster vaccination for
      children at ages 12 through 15 months; however, because of the recent shortage of
      Hib vaccines, many children have deferred the booster dose and therefore require
      catch-up vaccination. This report summarizes the indications for Hiberix use and
      provides guidance on Hib booster dose administration based on increasing vaccine
      supplies. Vaccination recommendations in this report update the previous advisory
      on Hib booster administration (June 26, 2009), which advised that children with
      deferred booster doses receive it at the next regularly scheduled visit.
      Vaccination providers are now recommended to begin recall of children in need of
      the booster dose when feasible and monovalent Hib vaccine supply in the office is
      adequate.

PMID- 19763079
TI  - Update: influenza activity--United States, April-August 2009.
AB  - The first 2009 pandemic influenza A (H1N1) virus infections were identified in
      the United States in April 2009. By August, the cumulative number of infections
      in the United States was estimated to be at least 1 million. This report provides
      an overview of influenza activity during April-August 2009 and recommendations
      for the upcoming 2009-10 influenza season. Pandemic H1N1 influenza activity
      peaked in the United States during May and June and declined during July and
      early August. However, levels of influenza activity remained above normal for
      summer months, and focal outbreaks were reported throughout the summer. During
      the last 2 weeks of August, pandemic H1N1 influenza activity increased in certain
      areas of the United States. Clinicians and public health officials should be
      aware that these recent increases might signal an early start to the 2009-10
      influenza season, with pandemic H1N1 influenza viruses predominating at least
      initially.

PMID- 19763080
TI  - Isolation and genetic manipulation of adult cardiac myocytes for confocal
      imaging.
AB  - Cardiac myocytes isolated from adult hearts are widely accepted as a model
      somewhere half way between embryonic and neonatal muscle cells on one side and a
      working heart on the other. Thus, cardiomyocytes serve as good models for cardiac
      cellular physiology and pathophysiology, for pharmaceutical investigations as
      well as for the exploration of transgenic animal models. Here we describe a
      method of isolating the cells from the heart. Furthermore we show how a genetic
      manipulation on cardiac myocytes can be performed without breeding a transgenic
      animal: This is the combination of long term culture (1 week) and adenoviral gene
      transfer. The latter one is described from the construction of the virus to the
      transduction of the cells. It can be used for the expression of genetically
      encoded biosensors (GEBs), fluorescent fusion proteins, but also for protein over
      expression and down regulation, e.g. using RNAi. Here we provide an example for
      the expression of a fusion protein staining a subcellular structure (Golgi). Such
      protein expression can be visualized by confocal imaging of z-stacks for a 3D
      reconstruction of subcellular structures. The protocol comprises state-of-the-art
      in cell culture, molecular biology and biophysics and thus provides an approach
      for exploring new horizons in cellular cardiology.

PMID- 19763081
TI  - Ligand-regulated oligomerization of beta(2)-adrenoceptors in a model lipid
      bilayer.
AB  - The beta(2)-adrenoceptor (beta(2)AR) was one of the first Family A G protein
      coupled receptors (GPCRs) shown to form oligomers in cellular membranes, yet we
      still know little about the number and arrangement of protomers in oligomers, the
      influence of ligands on the organization or stability of oligomers, or the
      requirement for other proteins to promote oligomerization. We used fluorescence
      resonance energy transfer (FRET) to characterize the oligomerization of purified
      beta(2)AR site-specifically labelled at three different positions with
      fluorophores and reconstituted into a model lipid bilayer. Our results suggest
      that the beta(2)AR is predominantly tetrameric following reconstitution into
      phospholipid vesicles. Agonists and antagonists have little effect on the
      relative orientation of protomers in oligomeric complexes. In contrast, binding
      of inverse agonists leads to significant increases in FRET efficiencies for most
      labelling pairs, suggesting that this class of ligand promotes tighter packing of
      protomers and/or the formation of more complex oligomers by reducing
      conformational fluctuations in individual protomers. The results provide new
      structural insights into beta(2)AR oligomerization and suggest a possible
      mechanism for the functional effects of inverse agonists.

PMID- 19763082
TI  - Regulation of endosomal clathrin and retromer-mediated endosome to Golgi
      retrograde transport by the J-domain protein RME-8.
AB  - After endocytosis, most cargo enters the pleiomorphic early endosomes in which
      sorting occurs. As endosomes mature, transmembrane cargo can be sequestered into
      inwardly budding vesicles for degradation, or can exit the endosome in membrane
      tubules for recycling to the plasma membrane, the recycling endosome, or the
      Golgi apparatus. Endosome to Golgi transport requires the retromer complex.
      Without retromer, recycling cargo such as the MIG-14/Wntless protein aberrantly
      enters the degradative pathway and is depleted from the Golgi. Endosome
      associated clathrin also affects the recycling of retrograde cargo and has been
      shown to function in the formation of endosomal subdomains. Here, we find that
      the Caemorhabditis elegans endosomal J-domain protein RME-8 associates with the
      retromer component SNX-1. Loss of SNX-1, RME-8, or the clathrin chaperone
      Hsc70/HSP-1 leads to over-accumulation of endosomal clathrin, reduced clathrin
      dynamics, and missorting of MIG-14 to the lysosome. Our results indicate a
      mechanism, whereby retromer can regulate endosomal clathrin dynamics through RME
      8 and Hsc70, promoting the sorting of recycling cargo into the retrograde
      pathway.

PMID- 19763083
TI  - Human RAP1 inhibits non-homologous end joining at telomeres.
AB  - Telomeres, the nucleoprotein structures at the ends of linear chromosomes,
      promote genome stability by distinguishing chromosome termini from DNA double
      strand breaks (DSBs). Cells possess two principal pathways for DSB repair:
      homologous recombination and non-homologous end joining (NHEJ). Several studies
      have implicated TRF2 in the protection of telomeres from NHEJ, but the underlying
      mechanism remains poorly understood. Here, we show that TRF2 inhibits NHEJ, in
      part, by recruiting human RAP1 to telomeres. Heterologous targeting of hRAP1 to
      telomeric DNA was sufficient to bypass the need for TRF2 in protecting telomeric
      DNA from NHEJ in vitro. On expanding these studies in cells, we find that
      recruitment of hRAP1 to telomeres prevents chromosome fusions caused by the loss
      of TRF2/hRAP1 from chromosome ends despite activation of a DNA damage response.
      These results provide the first evidence that hRAP1 inhibits NHEJ at mammalian
      telomeres and identify hRAP1 as a mediator of genome stability.

PMID- 19763084
TI  - Visualization of cargo concentration by COPII minimal machinery in a planar lipid
      membrane.
AB  - Selective protein export from the endoplasmic reticulum is mediated by COPII
      vesicles. Here, we investigated the dynamics of fluorescently labelled cargo and
      non-cargo proteins during COPII vesicle formation using single-molecule
      microscopy combined with an artificial planar lipid bilayer. Single-molecule
      analysis showed that the Sar1p-Sec23/24p-cargo complex, but not the Sar1p
      Sec23/24p complex, undergoes partial dimerization before Sec13/31p recruitment.
      On addition of a complete COPII mixture, cargo molecules start to assemble into
      fluorescent spots and clusters followed by vesicle release from the planar
      membrane. We show that continuous GTPase cycles of Sar1p facilitate cargo
      concentration into COPII vesicle buds, and at the same time, non-cargo proteins
      are excluded from cargo clusters. We propose that the minimal set of COPII
      components is required not only to concentrate cargo molecules, but also to
      mediate exclusion of non-cargo proteins from the COPII vesicles.

PMID- 19763085
TI  - E2F1 mediates DNA damage and apoptosis through HCF-1 and the MLL family of
      histone methyltransferases.
AB  - E2F1 is a key positive regulator of human cell proliferation and its activity is
      altered in essentially all human cancers. Deregulation of E2F1 leads to oncogenic
      DNA damage and anti-oncogenic apoptosis. The molecular mechanisms by which E2F1
      mediates these two processes are poorly understood but are important for
      understanding cancer progression. During the G1-to-S phase transition, E2F1
      associates through a short DHQY sequence with the cell-cycle regulator HCF-1
      together with the mixed-lineage leukaemia (MLL) family of histone H3 lysine 4
      (H3K4) methyltransferases. We show here that the DHQY HCF-1-binding sequence
      permits E2F1 to stimulate both DNA damage and apoptosis, and that HCF-1 and the
      MLL family of H3K4 methyltransferases have important functions in these
      processes. Thus, HCF-1 has a broader role in E2F1 function than appreciated
      earlier. Indeed, sequence changes in the E2F1 HCF-1-binding site can modulate
      both up and down the ability of E2F1 to induce apoptosis indicating that HCF-1
      association with E2F1 is a regulator of E2F1-induced apoptosis.

PMID- 19763086
TI  - Control of the pattern-recognition receptor EFR by an ER protein complex in plant
      immunity.
AB  - In plant innate immunity, the surface-exposed leucine-rich repeat receptor
      kinases EFR and FLS2 mediate recognition of the bacterial pathogen-associated
      molecular patterns EF-Tu and flagellin, respectively. We identified the
      Arabidopsis stromal-derived factor-2 (SDF2) as being required for EFR function,
      and to a lesser extent FLS2 function. SDF2 resides in an endoplasmic reticulum
      (ER) protein complex with the Hsp40 ERdj3B and the Hsp70 BiP, which are
      components of the ER-quality control (ER-QC). Loss of SDF2 results in ER
      retention and degradation of EFR. The differential requirement for ER-QC
      components by EFR and FLS2 could be linked to N-glycosylation mediated by STT3a,
      a catalytic subunit of the oligosaccharyltransferase complex involved in co
      translational N-glycosylation. Our results show that the plasma membrane EFR
      requires the ER complex SDF2-ERdj3B-BiP for its proper accumulation, and provide
      a demonstration of a physiological requirement for ER-QC in transmembrane
      receptor function in plants. They also provide an unexpected differential
      requirement for ER-QC and N-glycosylation components by two closely related
      receptors.

PMID- 19763087
TI  - Receptor quality control in the endoplasmic reticulum for plant innate immunity.
AB  - Pattern recognition receptors in eukaryotes initiate defence responses on
      detection of microbe-associated molecular patterns shared by many microbe
      species. The Leu-rich repeat receptor-like kinases FLS2 and EFR recognize the
      bacterial epitopes flg22 and elf18, derived from flagellin and elongation factor
      Tu, respectively. We describe Arabidopsis 'priority in sweet life' (psl) mutants
      that show de-repressed anthocyanin accumulation in the presence of elf18. EFR
      accumulation and signalling, but not of FLS2, are impaired in psl1, psl2, and
      stt3a plants. PSL1 and PSL2, respectively, encode calreticulin3 (CRT3) and UDP
      glucose:glycoprotein glycosyltransferase that act in concert with STT3A
      containing oligosaccharyltransferase complex in an N-glycosylation pathway in the
      endoplasmic reticulum. However, EFR-signalling function is impaired in weak psl1
      alleles despite its normal accumulation, thereby uncoupling EFR abundance control
      from quality control. Furthermore, salicylic acid-induced, but EFR-independent
      defence is weakened in psl2 and stt3a plants, indicating the existence of another
      client protein than EFR for this immune response. Our findings suggest a critical
      and selective function of N-glycosylation for different layers of plant immunity,
      likely through quality control of membrane-localized regulators.

PMID- 19763088
TI  - A longevity protein, Lag2, interacts with SCF complex and regulates SCF function.
AB  - SCF-type E3-ubiquitin ligases control numerous cellular processes through the
      ubiquitin-proteasome pathway. However, the regulation of SCF function remains
      largely uncharacterized. Here, we report a novel SCF complex-interacting protein,
      Lag2, in Saccharomyces cerevisiae. Lag2 interacts with the SCF complex under
      physiological conditions. Lag2 negatively controls the ubiquitylation activities
      of SCF E3 ligase by interrupting the association of Cdc34 to SCF complex.
      Overexpression of Lag2 increases unrubylated Cdc53, whereas deletion of lag2,
      together with the deletions of dcn1 and jab1, results in the accumulation of Rub1
      modified Cdc53. In vitro rubylation assays show that Lag2 inhibits the
      conjugation of Rub1 to Cdc53 in competition with Dcn1, which suggest that Lag2
      down-regulates the rubylation of Cdc53 rather than promoting derubylation.
      Furthermore, Dcn1 hinders the association of Lag2 to Cdc53 in vivo. Finally, the
      deletion of lag2 combined with the deletion of either dcn1 or rub1 suppresses the
      growth of yeast cells. These observations thus indicate that Lag2 has a
      significant function in regulating the SCF complex by controlling its ubiquitin
      ligase activities and its rubylation cycle.

PMID- 19763089
TI  - NEMO specifically recognizes K63-linked poly-ubiquitin chains through a new
      bipartite ubiquitin-binding domain.
AB  - An important property of NEMO, the core element of the IKK complex involved in NF
      kappaB activation, resides in its ability to specifically recognize poly
      ubiquitin chains. A small domain called NOA/UBAN has been suggested to be
      responsible for this property. We recently demonstrated that the C-terminal Zinc
      Finger (ZF) of NEMO is also able to bind ubiquitin. We show here by ZF swapping
      and mutagenesis that this represents its only function. While neither NOA nor ZF
      shows any preference for K63-linked chains, we demonstrate that together they
      form a bipartite high-affinity K63-specific ubiquitin-binding domain. A similar
      domain can be found in two other proteins, Optineurin and ABIN2, and can be
      freely exchanged with that of NEMO without interfering with its activity. This
      suggests that the main function of the C-terminal half of NEMO is to specifically
      bind K63-linked poly-ubiquitin chains. We also demonstrate that the recently
      described binding of NEMO to linear poly-ubiquitin chains is dependent on the NOA
      alone and does not require the presence of the ZF.

PMID- 19763090
TI  - dup(19)(q12q13.2): array-based genotype-phenotype correlation of a new possibly
      obesity-related syndrome.
AB  - Small supernumerary marker chromosomes (sSMCs) derived from the near-centromeric
      area of chromosome 2 are very rare. In addition, duplications of the 2p11.2-
      >q11.2 region have displayed considerable variability between patients harboring
      and lacking clinical findings. Moreover, constitutional duplication of the 19q12-
      >q13.2 region has previously only been described in two cases and was associated
      with delay of developmental milestones, corpus callosum anomalies, and obesity.
      Herein, we present a genotype-phenotype correlation in a patient harboring two
      sSMCs derived from chromosomes 2 and 14 or 22, respectively. The DNA was studied
      using G-banding, fluorescence in situ hybridization techniques, and array-based
      comparative genomic hybridization. A
      48,XX,+der(2)del(2)(p11)del(2)(q11.2),+der(14)t(14;19)(q11;q12)del(19)(q13.31) or
      48,XX,+der(2)del(2)(p11)del(2)(q11.2),+der(22)t(22;19)(q11;q12)del(19)(q13.31)
      was detected in the patient. The sSMC 14;19 or 22;19, with its centromere
      originating from either chromosome 14 or 22, encompassed a 13.56 megabase (Mb)
      19q derived region, harboring 263 genes, and the sSMC 2 a 2.71 Mb region
      including 29 genes. The patient had symptoms including a ventral septal defect,
      bilateral grade IV urinary reflux, corpus callosum agenesis, microphthalmia, and
      obesity. The 19q segment contained the genes AKT2, CEACAM1, CEBPA, LIPE, and
      TGFB1 which are involved in adipose tissue homeostasis and insulin resistance,
      and could potentially contribute to the obese phenotype observed. Array-based
      genetic characterization and long-term clinical evaluation with attention toward
      weight gain in patients with chromosome 19q duplications might in the future lead
      to the description of a obesity-associated genetic syndrome, something that could
      have implications in management and treatment of patients carrying a
      dup(19)(q12q13.2). Whether the der(2)(p11q11.2) contributes to the phenotype
      remains inconclusive.

PMID- 19763091
TI  - Estrogen reduces 11beta-hydroxysteroid dehydrogenase type 1 in liver and
      visceral, but not subcutaneous, adipose tissue in rats.
AB  - Following menopause, body fat is redistributed from peripheral to central depots.
      This may be linked to the age related decrease in estrogen levels. We
      hypothesized that estrogen supplementation could counteract this fat
      redistribution through tissue-specific modulation of glucocorticoid exposure. We
      measured fat depot masses and the expression and activity of the glucocorticoid
      activating enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) in fat
      and liver of ovariectomized female rats treated with or without 17beta-estradiol.
      11betaHSD1 converts inert cortisone, or 11-dehydrocorticosterone in rats into
      active cortisol and corticosterone. Estradiol-treated rats gained less weight and
      had significantly lower visceral adipose tissue weight than nontreated rats (P <
      0.01); subcutaneous adipose weight was unaltered. In addition, 11betaHSD1
      activity/expression was downregulated in liver and visceral, but not
      subcutaneous, fat of estradiol-treated rats (P < 0.001 for both). This
      downregulation altered the balance of 11betaHSD1 expression and activity between
      adipose tissue depots, with higher levels in subcutaneous than visceral adipose
      tissue of estradiol-treated animals (P < 0.05 for both), opposite the pattern in
      ovariectomized rats not treated with estradiol (P < 0.001 for mRNA expression).
      Thus, estrogen modulates fat distribution, at least in part, through effects on
      tissue-specific glucocorticoid metabolism, suggesting that estrogen replacement
      therapy could influence obesity related morbidity in postmenopausal women.

PMID- 19763092
TI  - Optimal waist circumference for prediction of metabolic syndrome in young Korean
      women with polycystic ovary syndrome.
AB  - The International Diabetes Federation consensus proposed an ethnically specific
      criteria of waist circumference (WC) for central obesity, but, the nationwide
      definition is still debated in Korea. For the detection of the optimal WC cutoff
      value, the nonadipose components of the metabolic syndrome (MS) were defined by
      modification of revised 2003 Rotterdam consensus as having two or more risk
      factors such as hypertension, hyperglycemia, and dyslipidemia without
      consideration of abdominal obesity. By using receiver-operating characteristic
      (ROC) curve analysis, cutoff points of WC and visceral fat area (VFA) for
      prediction of MS were 80 cm and 53.1 cm(2). WC cutoff points corresponding to VFA
      >53.1 and 100 cm(2) were 73.3 and 77.8 cm. The sensitivity and specificity of
      currently used value of WC 88 cm were 41.9 and 91.5%, suggesting that it could be
      too high in Korean population. Central obesity defined as WC >80 cm was
      significantly associated with nonadipose components of MS after adjustment for
      age, BMI, cholesterol, triglycerides, fasting insulin, and free testosterone
      levels. Central obesity with WC of >80 cm predicted the presence of nonadipose MS
      (odds ratio 16.6; 95% confidence interval (CI) 6.5-42.6). It was also significant
      (odds ratio 14.7; 95% CI 3.4-64.3) when we applied the WC value of 70 cm instead
      of 80 cm. In conclusion, WC of 80 and 70 cm could be appropriate cutoff points to
      identify the MS and visceral adiposity in Korean women with polycystic ovary
      syndrome (PCOS), respectively. Therefore, PCOS women with a WC over 70 cm should
      be closely monitored for the development of MS.

PMID- 19763093
TI  - Development and validation of a toddler silhouette scale.
AB  - The purpose of this study is to develop and validate a toddler silhouette scale.
      A seven-point scale was developed by an artist based on photographs of 15
      toddlers (6 males, 9 females) varying in race/ethnicity and body size, and a list
      of phenotypic descriptions of toddlers of varying body sizes. Content validity,
      age-appropriateness, and gender and race/ethnicity neutrality were assessed among
      180 pediatric health professionals and 129 parents of toddlers. Inter- and
      intrarater reliability and concurrent validity were assessed by having 138
      pediatric health professionals match the silhouettes with photographs of
      toddlers. Assessments of content validity revealed that most health professionals
      (74.6%) and parents of toddlers (63.6%) ordered all seven silhouettes correctly,
      and interobserver agreement for weight status classification was high (kappa =
      0.710, r = 0.827, P < 0.001). Most respondents reported that the scale
      represented toddlers aged 12-36 months (89%) and was gender (68.5%) and
      race/ethnicity (77.3%) neutral. The inter-rater reliability, based on matching
      silhouettes with photographs, was 0.787 (Cronbach's alpha) and the intrarater
      reliability was 0.855 (P < 0.001). The concurrent validity, based on the
      correlation between silhouette choice and the weight-for-length percentile of
      each toddler's photograph, was 0.633 (P < 0.001). In conclusion, a valid and
      reliable toddler silhouette scale that may be used for male or female toddlers,
      aged 12-36 months, of varying race/ethnicity was developed and evaluated. This
      scale may be used clinically or in research settings to assess parents'
      perception of and satisfaction with their toddler's body size. Interventions can
      be targeted toward parents who have inaccurate perceptions of or are dissatisfied
      with their toddler's body size.

PMID- 19763096
TI  - Assigning responsibility and credit.

PMID- 19763094
TI  - Dual-energy X-ray absorptiometry and anthropometric estimates of visceral fat in
      Black and White South African Women.
AB  - Visceral adipose tissue (VAT) is associated with increased risk for
      cardiovascular disease, and therefore, accurate methods to estimate VAT have been
      investigated. Computerized tomography (CT) is the gold standard measure of VAT,
      but its use is limited. We therefore compared waist measures and two dual-energy
      X-ray absorptiometry (DXA) methods (Ley and Lunar) that quantify abdominal
      regions of interest (ROIs) to CT-derived VAT in 166 black and 143 white South
      African women. Anthropometry, DXA ROI, and VAT (CT at L4-L5) were measured. Black
      women were younger (P < 0.001), shorter (P < 0.001), and had higher body fat (P <
      0.05) than white women. There were no ethnic differences in waist (89.7 +/- 18.2
      cm vs. 90.1 +/- 15.6 cm), waist:height ratio (WHtR, 0.56 +/- 0.12 vs. 0.54 +/-
      0.09), or DXA ROI (Ley: 2.2 +/- 1.5 vs. 2.1 +/- 1.4; Lunar: 2.3 +/- 1.4 vs. 2.3
      +/- 1.5), but black women had less VAT, after adjusting for age, height, weight,
      and fat mass (76 +/- 34 cm(2) vs. 98 +/- 35 cm(2); P < 0.001). Ley ROI and Lunar
      ROI were correlated in black (r = 0.983) and white (r = 0.988) women. VAT
      correlated with DXA ROI (Ley: r = 0.729 and r = 0.838, P < 0.01; Lunar: r = 0.739
      and r = 0.847, P < 0.01) in black and white women, but with increasing ROI
      android fatness, black women had less VAT. Similarly, VAT was associated with
      waist (r = 0.732 and r = 0.836, P < 0.01) and WHtR (r = 0.721 and r = 0.824, P <
      0.01) in black and white women. In conclusion, although DXA-derived ROIs
      correlate well with VAT as measured by CT, they are no better than waist or WHtR.
      Neither DXA nor anthropometric measures are able to accurately distinguish
      between high and low levels of VAT between population groups.

PMID- 19763097
TI  - Not all quiet on the noise front.
AB  - Phenotypic diversity exists even within isogenic populations of cells. Such
      nongenetic individuality may have wide implications for our understanding of many
      biological processes. The field of study concerned with the investigation of
      nongenetic individuality, also known as the 'biology of noise', is ripe with
      exciting scientific opportunities and challenges.

PMID- 19763099
TI  - When two keys fit one lock, surprises follow.

PMID- 19763100
TI  - Chemo-metabolic regulation of immune responses by Tregs.

PMID- 19763101
TI  - DNA-catalyzed hydrolysis of DNA phosphodiesters.

PMID- 19763104
TI  - Considering the evolution of regeneration in the central nervous system.
AB  - For many years the mammalian CNS has been seen as an organ that is unable to
      regenerate. However, it was also long known that lower vertebrate species are
      capable of impressive regeneration of CNS structures. How did this situation
      arise through evolution? Increasing cellular and molecular understanding of
      regeneration in different animal species coupled with studies of adult
      neurogenesis in mammals is providing a basis for addressing this question. Here
      we compare CNS regeneration among vertebrates and speculate on how this ability
      may have emerged or been restricted.

PMID- 19763105
TI  - Evolution of the neocortex: a perspective from developmental biology.
AB  - The enlargement and species-specific elaboration of the cerebral neocortex during
      evolution holds the secret to the mental abilities of humans; however, the
      genetic origin and cellular mechanisms that generated the distinct evolutionary
      advancements are not well understood. This article describes how novelties that
      make us human may have been introduced during evolution, based on findings in the
      embryonic cerebral cortex in different mammalian species. The data on the
      differences in gene expression, new molecular pathways and novel cellular
      interactions that have led to these evolutionary advances may also provide
      insight into the pathogenesis and therapies for human-specific neuropsychiatric
      disorders.

PMID- 19763106
TI  - New approaches to drug safety: a pharmacovigilance tool kit.
AB  - The importance of pharmacovigilance - the ongoing assessment of the safety of a
      marketed medicine - has been increasingly appreciated in recent years, owing in
      part to high-profile safety issues with widely used drugs. In response,
      strategies to improve the collection, integration and analysis of data related to
      post-marketing drug safety are being initiated or enhanced. In this article, we
      summarize the key tools that are available for pharmacovigilance, discuss which
      might be the most appropriate to use in different situations and consider the
      future directions of the field.

PMID- 19763107
TI  - Beyond debacle and debate: developing solutions in drug safety.
AB  - In the 5 years since the Vioxx debacle, efforts have been made to enhance drug
      safety. These include the introduction of legislation that expands the power of
      drug regulatory agencies, new data transparency standards and increased
      requirements for funding of post-marketing drug surveillance. Nevertheless, some
      doubt remains that these changes will be sufficient to address the increasing
      challenges in the field of drug safety. Here, from the perspective of a drug
      researcher, I discuss key areas for further development that could deliver long
      term solutions to these challenges: enhanced tools for the detection of safety
      signals, innovative phased drug launches, new risk stratification techniques and
      improved pharmacovigilance operations.

PMID- 19763109
TI  - Brain and disease: the long path to discovery and treatment.

PMID- 19763112
TI  - Neuroimaging placebo effects: new tools generate new questions.

PMID- 19763113
TI  - Benefits exceed risks of newer antidepressant medications in youth--maybe.

PMID- 19763114
TI  - Benefits exceed risks of newer antidepressant medications in youth--maybe not.

PMID- 19763115
TI  - Predicting age-specific dosing of antipsychotics.
AB  - Antipsychotic medications are the standard of care for both acute and maintenance
      treatment of schizophrenia, the latter requiring an indefinite treatment across a
      patient's life span. However, dosing and tolerability of antipsychotics have been
      studied primarily in younger patients, and very limited data are available for
      age- and phase-specific dosing. This leaves the clinician with no guidance on
      dose adjustment as patients grow older-an issue of critical importance,
      especially in light of recent concerns about increased morbidity and mortality
      associated with antipsychotics.

PMID- 19763116
TI  - Pharmacotherapy for depressed pregnant women: overcoming obstacles to gathering
      essential data.
AB  - Approximately 3% of pregnant women take antidepressant medications. Information
      on the impact of antidepressants on short- and long-term maternal and offspring
      outcomes is highly desirable but neglected. The position that the dearth of
      treatment information is of greater concern than the risks to pregnant subjects
      involved in medical research is gaining support. Mandating the collection of
      reproductive outcome data in exposed childbearing women is an overdue step toward
      societal responsibility to our most vulnerable members.

PMID- 19763117
TI  - The Coalition Against Major Diseases: developing tools for an integrated drug
      development process for Alzheimer's and Parkinson's diseases.
AB  - Aiming to emulate the successful accelerated development of HIV/AIDS drugs, the
      Critical Path Institute (C-Path), in collaboration with the Engelberg Center for
      Health Care Reform at the Brookings Institution, has formed the Coalition Against
      Major Diseases (CAMD). Members include 6 nonprofit groups representing patients'
      interests, 15 leading pharmaceutical companies, the US Food and Drug
      Administration (FDA), the European Medicines Agency (EMEA), 2 institutes of the
      National Institutes of Health (NIH)-the National Institute on Aging (NIA) and the
      National Institute of Neurological Disorders and Stroke (NINDS)-and
      representatives from academia. The coalition's purpose is to transform the drug
      development paradigm for neurodegenerative diseases and serve as a model for
      other major diseases.

PMID- 19763118
TI  - Left ventricular function in gestational hypertension: serial echocardiographic
      study.
AB  - BACKGROUND: Gestational hypertension (GH) is associated with hemodynamic changes,
      and alterations of systolic and diastolic left ventricular (LV) function.
      However, the magnitude and pattern of changes of different parameters of LV
      function and contractility in this patient population have not been fully
      clarified. METHODS: Thirty-five pregnant women with GH underwent three
      echocardiographic examinations, in second and third trimester of pregnancy, and 1
      month after delivery. Twelve normotensive pregnant women served as gestational
      age-matched controls. Hemodynamic parameters and standard indexes of LV systolic
      and diastolic function were analyzed. Additionally, we have measured peak
      systolic velocity of mitral annulus (S'), end-systolic elastance (Ees), and early
      transmitral to early lengthening velocity of mitral annulus ratio (E/E') as
      parameters of longitudinal function, contractility, and filling, respectively.
      RESULTS: Women with GH had initially higher body weight, blood pressure, and
      heart rate (P < 0.005, P < 0.0001, and P = 0.011, respectively). Temporal
      analysis of different echocardiographic parameters revealed increase in wall
      thickness from baseline to second measurement, with consequential increase in LV
      mass in women with GH (P = 0.014 for septum, P = 0.010 for posterior wall, and P
      = 0.09 for LV mass). No significant changes of LV volumes, ejection fraction
      (EF), transmitral flow parameters, S', Ees, and E/E' were observed throughout the
      follow-up in both groups (P = nonsignificant for all). Importantly, pattern of
      changes was similar in both groups for all examined parameters (P =
      nonsignificant between groups, for all). CONCLUSIONS: It appears that changes of
      LV longitudinal function, filling, and contractility during pregnancy are not
      significant and not influenced by GH.

PMID- 19763119
TI  - Aldosterone contributes to blood pressure variance and to likelihood of
      hypertension in normal-weight and overweight African Americans.
AB  - BACKGROUND: Hypertension and obesity are highly prevalent among African Americans
      (AAs). We have previously reported that both plasma aldosterone (PA) and body
      mass index (BMI) are higher in hypertensive than in normotensive AAs. This study
      evaluates the relative contributions of adiposity and PA to hypertension in AAs.
      METHODS: A total of 466 AAs (50% hypertensive, 51% women) were evaluated in a
      Clinical Research Center by stratifying them into three subgroups based on BMI
      (normal weight, overweight, and obese). Anthropometric measurements, ambulatory
      blood pressure (BP), fasting glucose, insulin, 24-h urine sodium and potassium,
      creatinine clearance, standing PA and plasma renin activity (PRA) were measured.
      Insulin resistance was estimated by the homeostasis model assessment. RESULTS:
      Compared to normotensives, hypertensives had higher BMI, waist circumference
      (WC), and were more insulin resistant (P < or = 0.01). When stratified by BMI,
      hypertensives in each BMI strata had higher PA (P < or = 0.05) and lower PRA (P <
      or = 0.01) compared to normotensives. Compared to normotensives, WC was greater
      in overweight and obese hypertensives, but not in normal-weight hypertensives. In
      the overall sample, age, WC, PA, and PRA were the major contributors to BP
      variance and to hypertension. Among normal-weight subjects, PA and PRA
      significantly predicted BP and the odds ratio for hypertension, whereas WC had no
      predictive value. CONCLUSIONS: PA, but not WC, is associated with BP and
      likelihood of hypertension in normal-weight AAs, whereas both WC and PA are
      predictive of hypertension in overweight and obese individuals. This suggests
      that aldosterone antagonists may be useful for the treatment of hypertension
      among AAs, regardless of BMI.

PMID- 19763120
TI  - Correlation between blood pressure responses to dietary sodium and potassium
      intervention in a Chinese population.
AB  - BACKGROUND: Blood pressure (BP) responses to dietary sodium and potassium intake
      vary among individuals. We examined the correlation between BP responses to
      dietary low-sodium, high-sodium, and potassium supplementation interventions in a
      feeding study. METHODS: A total of 1,906 Chinese aged > or = 16 years
      participated in the dietary intervention that included a 7-day low-salt
      intervention (51.3 mmol/day), a 7-day high-salt intervention (307.8 mmol/day),
      and a 7-day high-salt plus potassium supplementation (60 mmol/day) intervention.
      BP was measured nine times during the 3-day baseline observation and during the
      last 3 days of each intervention phase using a random-zero sphygmomanometer.
      RESULTS: The correlation coefficients (95% confidence intervals (CIs)) of the BP
      responses to low-sodium and high-sodium interventions were -0.47 (-0.51 to 
      0.44), -0.47 (-0.50 to -0.43), and -0.45 (-0.49 to -0.42) for systolic BP (SBP),
      diastolic BP (DBP), and mean arterial pressure (MAP), respectively (all P <
      0.0001). The correlation coefficients (95% CI) of the BP responses to high-sodium
      intervention and potassium supplementation were -0.52 (-0.56 to -0.49), -0.48 (
      0.52 to 0.45), and -0.52 (-0.55 to -0.48) for SBP, DBP, and MAP, respectively
      (all P < 0.0001). The kappa coefficients were moderate, varying from 0.28 to
      0.34, between BP responses to low-sodium and high-sodium interventions (all P <
      0.0001). CONCLUSIONS: These results indicate there is a moderate correlation
      between BP responses to low-sodium and to high-sodium interventions, and BP
      responses to high-sodium intervention and potassium supplementation. Furthermore,
      our study suggests that individuals who were more sensitive to high-sodium diet
      might benefit more from a low-sodium and/or high-potassium intervention aimed at
      lowering BP levels.

PMID- 19763121
TI  - Blood pressure control determines improvement in diastolic dysfunction in early
      hypertension.
AB  - BACKGROUND: Diastolic dysfunction is common in early hypertension. We
      hypothesized that improvement in diastolic dysfunction is blood pressure (BP)
      dependent and may occur early with treatment in newly diagnosed untreated
      hypertensive patients. METHODS: Forty untreated hypertensive subjects (age 52 +/-
      1.4 years, mean +/- s.e.m.) with diastolic dysfunction based on Canadian
      Consensus Guidelines, received either bendroflumethiazide 2.5 mg (1.25 mg for the
      first month), or candesartan 16 mg (8 mg for the first month). Left ventricular
      (LV) structure and function, early diastolic velocity (E') and systolic velocity,
      and systolic myocardial velocity (Sm) were assessed echocardiographically using M
      mode, 2-dimensional, and tissue Doppler imaging (TDI) before and at 1 and 3
      months following treatment. RESULTS: Antihypertensive treatment reduced BP
      significantly at 3 months (168 +/- 2/97 +/- 1-143 +/- 2/86 +/- 1 mm Hg, P <
      0.0001). Both drugs had similar and significant effects on TDI E' which increased
      from 7.8 +/- 0.2 to 10 +/- 0.3 cm/s (P < 0.001). The improvement in TDI E' was
      independent of LV mass index (LVMI) regression but was significantly related to
      the improvement in Sm (r = 0.73, P < 0.0001) and the fall in systolic BP (R =
      0.51, P < 0.001). Normalization of diastolic function was associated with better
      control of BP (130 +/- 4/81 +/- 2 mm Hg vs. 149 +/- 2/88 +/- 1 mm Hg, P < 0.05).
      In a stepwise regression model, reduction in systolic BP (P < 0.001) and TDI Sm
      (P < 0.0001) emerged as independent determinants of improvement in TDI E' with no
      contribution from age, gender or change in relative wall thickness (RWT) (R(2) =
      0.68, P < 0.0001). CONCLUSIONS: Achieving good BP control and enhancement in
      systolic function determines the improvement in diastolic function in early
      hypertension.

PMID- 19763122
TI  - Diabetes: incidence of childhood type 1 diabetes: a worrying trend.

PMID- 19763123
TI  - Cancer: QTNM: a simplified TNM or just another staging system?

PMID- 19763124
TI  - Diabetes: hypoglycemia and dementia in type 2 diabetes: chick or egg?

PMID- 19763125
TI  - Nutrition: US recommendations fail to correct vitamin D deficiency.

PMID- 19763126
TI  - The Diabetes Control and Complications Trial: the gift that keeps giving.
AB  - The Diabetes Control and Complications Trial (DCCT) recruited its first patients
      in 1983. In 1993, the investigators reported that intensive glycemic treatment of
      patients with type 1 diabetes mellitus was superior to conventional therapy in
      preventing the development of microvascular and neurological complications and
      thus provided definitive proof of the relationship between hyperglycemia and the
      subsequent risk of diabetic retinopathy, nephropathy and neuropathy. The value of
      this study, however, did not end there. After the original trial, most
      participants of the DCCT continued to be followed up in the Epidemiology of
      Diabetes Interventions and Complications (EDIC) study, which demonstrated the
      long-term benefits of close glycemic control and provided observational data of a
      large epidemiological cohort of patients with type 1 diabetes mellitus. Stored
      samples from the DCCT have also provided an invaluable resource for the
      identification of new markers of the disease. Recently, the complete dataset of
      the DCCT and of the initial years of the EDIC have been made publicly available,
      which allowed independent investigators to help answer their own questions about
      diabetes. In conclusion, the DCCT continues to provide new insights into type 1
      diabetes mellitus, which are of benefit to patients over a quarter of a century
      after the trial was started.

PMID- 19763127
TI  - Somatostatin analog and pegvisomant combination therapy for acromegaly.
AB  - Optimal biochemical control cannot be attained by long-acting somatostatin analog
      monotherapy in a large proportion of patients with acromegaly. Such therapy might
      result in increased mortality, poor control of signs and symptoms of disease and
      decreased quality of life. Combination treatment with somatostatin analogs and
      pegvisomant (a growth-hormone-receptor antagonist) is, however, highly effective
      at normalizing the level of insulin-like growth factor I in over 90% of patients
      and might also have a favorable effect on quality of life in those with
      biochemically controlled acromegaly. Moreover, whereas pegvisomant monotherapy
      does not lead to a decrease in the size of the pituitary tumor, combination
      therapy with somatostatin analogs results in a clinically relevant decrease in
      tumor size in about 20% of patients. The main adverse effects of combination
      treatment are transient elevations in the levels of transaminases, which occur in
      about 15% of patients, especially in those with diabetes mellitus. In this
      Review, we discuss the available data on the long-term efficacy and safety of
      somatostatin analog-pegvisomant combination treatment and its potential use in
      patients with acromegaly.

PMID- 19763128
TI  - A case of diabetic Charcot arthropathy of the foot and ankle.
AB  - BACKGROUND: A 61-year-old man with type 2 diabetes mellitus presented to a
      diabetic foot clinic 1 year after he injured his left foot in a slip injury.
      Examination showed collapse of the longitudinal arch with a rocker bottom
      deformity and a plantar ulcer under the plantar midfoot bony prominence.
      INVESTIGATIONS: Radiographs of the foot. DIAGNOSIS: Diabetic Charcot arthropathy
      with rocker bottom deformity and plantar midfoot ulcer. MANAGEMENT: The ulcer was
      initially treated by debridement and immobilization. Subsequently, the patient
      underwent surgery that consisted of plantar midfoot ostectomy to remove the bony
      prominence that had caused the ulcer, and midfoot osteotomy with realignment
      arthrodesis to reconstruct the longitudinal arch.

PMID- 19763129
TI  - Heart function influenced by selective mid-cervical left vagus nerve stimulation
      in a human case study.

PMID- 19763130
TI  - Olmesartan reduces oxidative stress in the brain of stroke-prone spontaneously
      hypertensive rats assessed by an in vivo ESR method.
AB  - We previously showed that oxidative stress in the brain is involved in the neural
      mechanisms of hypertension. Therefore, olmesartan, an angiotensin type 1 receptor
      blocker, might affect oxidative stress in the brains of stroke-prone
      spontaneously hypertensive rats (SHRSP). Here, we evaluated the effects of
      olmesartan treatment using an in vivo electron spin resonance (ESR)/spin probe
      technique. Two groups of SHRSP were treated with either olmesartan (10 mg kg(-1)
      day(-1)) or hydralazine (Hyd, 20 mg kg(-1) day(-1))/hydrochlorothiazide (HCT, 4.5
      mg (-1)kg day(-1)) for 30 days (n=5 for each). Systolic blood pressure decreased
      similarly in both groups after treatment. Heart rate and urinary norepinephrine
      (NE) excretion increased in rats treated with Hyd/HCT, but not in those treated
      with olmesartan. The in vivo ESR signal decay rates of the blood-brain barrier
      permeable spin probe methoxycarbonyl-PROXYL were significantly higher in SHRSP
      brains than in age-matched normotensive Wistar-Kyoto rat brains (P<0.01; n=6 for
      each). Olmesartan attenuated the ESR signal decay rates in SHRSP brains, but
      Hyd/HCT did not. Intracerebroventricular infusion of active form of olmesartan,
      RNH-6270, reduced blood pressure and NE excretion, and the ESR signal decay rate
      was reduced in SHRSP brains. These findings indicate that olmesartan has anti
      oxidative property in the brain without stimulating reflex-mediated sympathetic
      activity in SHRSP.

PMID- 19763131
TI  - Misregulation of the arginase pathway in tissues of spontaneously hypertensive
      rats.
AB  - There is a growing evidence that arginase has a role in the pathophysiology of
      cardiovascular diseases including hypertension. We recently reported arginase
      upregulation in aortas from hypertensive spontaneously hypertensive rats (SHRs).
      The aim of this study was to determine whether arginase abnormalities occur in
      other tissues of SHR, including the target organs of hypertension. Experiments
      were conducted on 5-, 10-, 19- and 26-week-old SHRs and Wistar-Kyoto (WKY) rats.
      Arginase activity and expression were evaluated in heart, kidney, liver, lung and
      brain tissue extracts. To investigate the role of blood pressure by itself in
      arginase abnormalities, arginase activity was determined in 10-week-old SHRs
      previously treated with hydralazine (20 mg kg(-1) per day, for 5 weeks). Compared
      with WKY rats, cardiac arginase activity was higher in hypertensive SHRs aged 10
      weeks (+46%, P<0.05), 19 weeks (+29%, P<0.05) and 26 weeks (+23%, NS). Similar
      results were found in lungs in which arginase activity was increased in SHRs aged
      10 weeks (+39%, P<0.05), 19 weeks (+49%, P<0.05) and 26 weeks (+36%, P<0.05)
      compared with WKY rats. The changes in arginase activity in these tissues were
      not associated with changes in enzyme expression. The prevention of hypertension
      by hydralazine blunted the increase in arginase activity in the hearts but not in
      the lungs. No change in arginase activity/expression was found in the kidney,
      liver or brain. In conclusion, this study shows that increased arginase activity
      is not restricted to large vessels in SHRs and suggests that cardiac arginase
      activity is hemodynamic sensitive.

PMID- 19763132
TI  - Safety and benefits of a tablet combining losartan and hydrochlorothiazide in
      Japanese diabetic patients with hypertension.
AB  - This study was conducted to determine the effects of a tablet combining
      losartan/hydrochlorothiazide (L/HCTZ) in comparison with losartan alone in
      Japanese diabetic patients with hypertension. Thirty consecutive Japanese
      diabetic patients with hypertension were randomly assigned to group A, receiving
      losartan alone for the first 3 months, then L/HCTZ for the next 3 months, or
      group B, receiving L/HCTZ for the first 3 months, then losartan alone for the
      next 3 months. Clinical and biological parameters were obtained before, and 3 and
      6 months after the start of this study. The decreases in systolic and diastolic
      blood pressure (BP) during treatment with L/HCTZ were significantly greater than
      in treatment with losartan alone. Both treatments significantly and similarly
      decreased urinary albumin excretion, the cardio-ankle vascular index (CAVI) and
      augmentation index (AI). There was no significant difference in metabolic change
      during both the mono- and combination pharmacotherapies. The tablet combining
      L/HCTZ significantly reduced systolic and diastolic BP compared with the losartan
      monotherapy, and offered benefits similar to losartan monotherapy for
      albuminuria, arterial stiffness assessed by the CAVI and AI, and metabolic
      effects. Thus, the L/HCTZ tablet could be a useful drug for Japanese diabetic
      patients with hypertension.

PMID- 19763133
TI  - Development and validation of a cardiovascular risk prediction model for
      Japanese: the Hisayama study.
AB  - The objective of this paper is to develop a new risk prediction model of
      cardiovascular disease and to validate its performance in a general population of
      Japanese. The Hisayama study is a population-based prospective cohort study. A
      total of 2634 participants aged 40 years or older were followed up for 14 years
      for incident cardiovascular disease (stroke and coronary heart disease
      (myocardial infarction, coronary revascularization and sudden cardiac death)). We
      used data among a random two-thirds (the derivation cohort, n=1756) to develop a
      new risk prediction model that was then tested to compare observed and predicted
      outcomes in the remaining one-third (the validation cohort, n=878). A
      multivariable cardiovascular risk prediction model was developed that
      incorporated age, sex, systolic blood pressure, diabetes, low-density lipoprotein
      cholesterol, high-density lipoprotein cholesterol and smoking. We assessed the
      performance of the model for predicting individual cardiovascular event among the
      validation cohort. The risk prediction model demonstrated good discrimination (c
      statistic=0.81; 95% confidence interval, 0.77 to 0.86) and calibration (Hosmer
      Lemeshow chi(2)-statistic=6.46; P=0.60). A simple risk score sheet based on the
      cardiovascular risk prediction model was also presented. We developed and
      validated a new cardiovascular risk prediction model in a general population of
      Japanese. The risk prediction model would provide a useful guide to estimate
      absolute risk of cardiovascular disease and to treat individual risk factors.

PMID- 19763134
TI  - Association of PLA2G7 polymorphisms with carotid atherosclerosis in hypertensive
      Japanese.
AB  - Although the plasma platelet-activating factor-acetylhydrolase (pPAF-AH) gene
      (PLA2G7) polymorphisms are reportedly associated with atherosclerotic diseases,
      their effects in hypertensive patients have not been well examined. Thus, we
      genotyped V279F, a loss-of-function mutation commonly seen in the Japanese, and
      I198T and A379V commonly seen in Caucasians, and investigated the (1) ethnic
      differences in the frequencies and (2) association of these variants with
      prevalence of carotid plaque in 733 treated hypertensive Japanese patients. The
      distribution of V279F (V allele 75.1% and F allele 24.9%) in hypertensive
      patients was similar to that previously reported in the healthy Japanese;
      however, allele frequencies of I198T (I allele 71.7% and T allele 28.3%) and
      A379V (A allele 84.7% and V allele 15.3%) were markedly different from those
      reported in Caucasians. In addition, V279F and I198T showed a strong linkage
      disequilibrium (D'=1.0, r(2)=0.89). The phenotypes showed no difference among
      genotypes for each polymorphism except for the blood pressure level in I198T in
      women. Carotid plaque was significantly more prevalent in subjects with 279F and
      198T than in those with the wild type among men but not women, whereas A379V did
      not affect it. In multivariate logistic regression analyses, 279F and 198T were
      detected as an independent risk factor even after adjustments for other
      atherosclerotic risk factors in men. Taken together, our data suggest an ethnic
      difference and the possible involvement of genetic polymorphisms of PLA2G7 in the
      prevalence of carotid atherosclerosis in the hypertensive Japanese, especially in
      men.

PMID- 19763135
TI  - Highly purified eicosapentaenoic acid reduces cardio-ankle vascular index in
      association with decreased serum amyloid A-LDL in metabolic syndrome.
AB  - A recent clinical trial revealed that highly purified eicosapentaenoic acid
      (EPA), an n-3 polyunsaturated fatty acid, reduces the incidence of cardiovascular
      diseases. However, the detailed mechanism underlying the anti-atherogenic effect
      of EPA is still poorly understood. In this study, we examined the effect of EPA
      on cardio-ankle vascular index (CAVI), a new index of arterial stiffness that is
      less influenced by blood pressure (BP), as well as on serum amyloid A-low-density
      lipoprotein (SAA-LDL), an oxidized LDL (oxLDL), in the metabolic syndrome. Ninety
      two obese Japanese subjects with metabolic syndromes were randomly divided into
      two groups (n=46): the EPA-treated group (1.8 g administered daily for 3 months)
      and the control group. Measurements were taken to assess the changes in glucose
      lipid metabolism, SAA-LDL, C-reactive protein (CRP), leptin, adiponectin and
      pulse wave velocity (PWV), and CAVI. EPA treatment significantly reduced the
      levels of immunoreactive insulin, triglycerides, SAA-LDL, CRP, PWV and CAVI and
      increased the levels of adiponectin relative to the control group for 3 months
      (P<0.05). Stepwise multivariate linear regression analysis revealed that the only
      significant determinant for a decrease in CAVI by EPA is a reduction in SAA-LDL
      (P<0.05). Moreover, the EPA-induced reduction of SAA-LDL was only significantly
      correlated with a decrease in total cholesterol and an increase in adiponectin
      (P<0.05). This study is the first demonstration that EPA improves arterial
      stiffness and is less influenced by BP, possibly through the suppression of SAA
      LDL, thereby leading to a reduction in the frequency of cardiovascular disease
      development in metabolic syndrome.

PMID- 19763136
TI  - Does eicosapentaenoic acid truly reduce atherosclerosis?

PMID- 19763137
TI  - Purinergic receptor P2Y, G-protein coupled, 2 (P2RY2) gene is associated with
      cerebral infarction in Japanese subjects.
AB  - G-protein-coupled purinergic receptor P2Y2 (P2RY2) has an important role in the
      process of atherosclerosis related to cerebral infarction (CI). The aim of this
      study was to investigate the relationship between the P2RY2 gene and CI through a
      haplotype-based case-control study, including the separate analysis of two gender
      groups. A total of 237 CI patients and two control groups (control 1, 254;
      control 2, 255) were genotyped for five single nucleotide polymorphisms (SNPs) in
      the human P2RY2 gene (rs4944831, rs1783596, rs4944832, rs4382936, rs10898909).
      Among women, the distribution of the dominant rs4944832 phenotype (GG vs. GA+AA)
      differed significantly between the CI patients and the control 1 group (P=0.043)
      and between the CI patients and the control 2 group (P=0.029). Logistic
      regression analysis showed that the GG genotype of rs4944832 was significantly
      more prevalent in the female CI patients than in the control 1 (P=0.021) and
      control 2 groups (P=0.005). For all subjects, the overall distribution of the
      haplotype established by rs1783596-rs4382936-rs10898909 was significantly
      different between the CI patients and the control 1 group (P=0.027). For all
      subjects, the frequency of the T-A-G haplotype (rs1783596-rs4382936-rs10898909)
      was also significantly higher (P=0.031), whereas the frequency of the T-C-G
      haplotype (rs1783596-rs4382936-rs10898909) was significantly lower (P=0.029) in
      the CI patients than in the control 1 group. The present results indicate that
      the T-A-G haplotype of the human P2RY2 gene is a susceptibility haplotype for CI
      in Japanese subjects, and that the GG genotype is a genetic marker for CI,
      particularly in Japanese women.

PMID- 19763138
TI  - Safflower seed polyphenols (N-(p-coumaroyl)serotonin and N-feruloylserotonin)
      ameliorate atherosclerosis and distensibility of the aortic wall in Kurosawa and
      Kusanagi-hypercholesterolemic (KHC) rabbits.
AB  - Pulse wave velocity (PWV) has been used clinically as a direct measure of
      arterial stiffness. We investigated the inhibitory effects of defatted safflower
      seed extract (SSE) and serotonin derivatives (N-(p-coumaroyl)serotonin, N
      feruloylserotonin; CS+FS), which are the active components in SSE, on
      hypercholesterolemia and atherosclerosis, using PWV in Kurosawa and Kusanagi
      hypercholesterolemic (KHC) rabbits. SSE and CS+FS were supplemented with a
      commercial diet containing 0.5% cholesterol for 8 weeks in male KHC rabbits, aged
      2 months. Pulse waves were recorded at different aortic positions using two
      catheters with micromanometers under pentobarbital anesthesia. The
      atherosclerotic lesioned area in the aorta was significantly reduced in the SSE
      and CS+FS groups, without significant changes in serum cholesterol and
      triglyceride levels among the three groups after supplementation. Local PWV
      (LPWV) in the middle thoracic and distal abdominal aortas was significantly
      smaller in the SSE and CS+FS groups than in the control group. PWV in the entire
      aorta was also significantly lower in the SSE and CS+FS groups, compared with
      that in the control group. Pressure-strain elastic modulus, an index of wall
      distensibility, was significantly lower in the middle thoracic and middle
      abdominal aortas in the SSE and CS+FS groups than in the control group. Wall
      thickness was also significantly smaller in the middle thoracic aorta in the SSE
      and CS+FS groups compared with that in the control group. Serotonin derivatives
      inhibited the progress of atherosclerosis and ameliorated wall distensibility,
      which contributed, in part, to the lowering of LPWV. Serotonin derivatives may be
      beneficial in improving vascular distensibility and in reducing cardiovascular
      risk.

PMID- 19763140
TI  - Conformational stability and activity of p73 require a second helix in the
      tetramerization domain.
AB  - p73 and p63, the two ancestral members of the p53 family, are involved in
      neurogenesis, epithelial stem cell maintenance and quality control of female germ
      cells. The highly conserved oligomerization domain (OD) of tumor suppressor p53
      is essential for its biological functions, and its structure was believed to be
      the prototype for all three proteins. However, we report that the ODs of p73 and
      p63 differ from the OD of p53 by containing an additional alpha-helix that is not
      present in the structure of the p53 OD. Deletion of this helix causes a
      dissociation of the OD into dimers; it also causes conformational instability and
      reduces the transcriptional activity of p73. Moreover, we show that ODs of p73
      and p63 strongly interact and that a large number of different heterotetramers
      are supported by the additional helix. Detailed analysis shows that the
      heterotetramer consisting of two homodimers is thermodynamically more stable than
      the two homotetramers. No heterooligomerization between p53 and the p73/p63
      subfamily was observed, supporting the notion of functional orthogonality within
      the p53 family.

PMID- 19763139
TI  - Adenosine signaling and function in glial cells.
AB  - Despite major advances in a variety of neuroscientific research fields, the
      majority of neurodegenerative and neurological diseases are poorly controlled by
      currently available drugs, which are largely based on a neurocentric drug design.
      Research from the past 5 years has established a central role of glia to
      determine how neurons function and, consequently, glial dysfunction is implicated
      in almost every neurodegenerative and neurological disease. Glial cells are key
      regulators of the brain's endogenous neuroprotectant and anticonvulsant
      adenosine. This review will summarize how glial cells contribute to adenosine
      homeostasis and how glial adenosine receptors affect glial function. We will then
      move on to discuss how glial cells interact with neurons and the vasculature, and
      outline new methods to study glial function. We will discuss how glial control of
      adenosine function affects neuronal cell death, and its implications for
      epilepsy, traumatic brain injury, ischemia, and Parkinson's disease. Eventually,
      glial adenosine-modulating drug targets might be an attractive alternative for
      the treatment of neurodegenerative diseases. There are, however, several major
      open questions that remain to be tackled.

PMID- 19763141
TI  - mtDNA G10398A variant in African-American women with breast cancer provides
      resistance to apoptosis and promotes metastasis in mice.
AB  - We investigated the effect of the mitochondrial DNA (mtDNA) polymorphism G10398A
      found in African-American women with aggressive breast cancer on apoptosis and
      tumorigenesis. We generated human cytoplasmic hybrid (cybrid) by repopulation of
      recipient rho(0) cells (devoid of mtDNA) with donor mtDNA derived from patients
      with breast cancer harboring the G10398A polymorphism. We investigated a number
      of functional phenotypes of the G10398A cybrid. The G10398A cybrid showed a
      slower proliferation rate and progression through the cell cycle, as well as
      increased complex I activity, increased levels of reactive oxygen species and
      depolarized mitochondria. The G10398A cybrid also showed resistance to apoptosis
      triggered by etoposide. Resistance to apoptosis was mediated by Akt activation.
      In addition, our studies showed that the G10398A cybrid cells form an increased
      number of anchorage-independent colonies in vitro and metastases in mice.
      Together our studies suggest that the G10398A variant confers resistance to
      apoptosis and promotes metastasis.

PMID- 19763142
TI  - Mutational screening of VSX1 in keratoconus patients from the European
      population.
AB  - PURPOSE: To perform mutational screening of the visual system homeobox gene 1
      (VSX1; MIM#605020) in patients with sporadic and familial keratoconus
      (MIM#148300) in a European population and, for the first time, report the
      mutational analysis of the two newly identified VSX1exons. METHODS: VSX1sequence
      variants in patients with keratoconus were evaluated by direct sequencing of the
      entire coding region, including two novel exons. In familial keratoconus cases,
      segregation of potentially pathogenic VSX1variants was assessed to determine
      pathogenicity. Transcript analysis was carried out on splice site and synonymous
      sequence variants not detected in controls. RESULTS: A total of 66 unrelated
      patients with keratoconus from the European population (27 with familial
      keratoconus; 39 with sporadic keratoconus) were analysed for VSX1 mutations. Four
      sequence variants were not observed in 100 healthy control individuals: c.432C>G
      (p.D144E), c.479G>A (p.G160D), c.789C>T (p.S263S), and an intronic change c.844
      13T>A (numbered with respect to NM_014588). Segregation was not detected for
      p.D144E and c.844-13T>A. The change in p.G160D was observed in two patients with
      sporadic keratoconus. Although predicted to alter VSX1 splicing, p.S263S had no
      effect on transcript processing. Four known SNPs were detected and the following
      polymorphic variants were observed in keratoconus patients and controls: c.711T>A
      (NM_199425; p.P237P), c.844-5_-6insT (NM_014588), c.*28G>T (DQ854811/DQ854812),
      and c.*50G>A (DQ854809/DQ854810). CONCLUSIONS: VSX1has a minor role in
      keratoconus pathogenesis. The pathogenicity of p.G160D remains controversial and
      this change may represent a rare polymorphism or genetic modifier. Further
      evidence is provided that the previously reported variant, p.D144E, is a
      polymorphism.

PMID- 19763143
TI  - Just say NO: nitric oxide regulation of Hsp90.

PMID- 19763144
TI  - Molecular aspects of male fertility. International Workshop on Molecular
      Andrology.

PMID- 19763145
TI  - Genomics for citizens. Providing the public with more and better knowledge to
      address the challenges of the twenty-first century.

PMID- 19763146
TI  - The role of means and goals in technology acceptance. A differentiated landscape
      of public perceptions of pharming.

PMID- 19763147
TI  - Fusion enzymes containing HSV-1 thymidine kinase mutants and guanylate kinase
      enhance prodrug sensitivity in vitro and in vivo.
AB  - Herpes simplex virus thymidine kinase (HSVTK) with ganciclovir (GCV) is currently
      the most widely used suicide gene/prodrug system in cancer gene therapy. A major
      limitation in this therapy is the inefficient activation of GCV by HSVTK to its
      active antimetabolites. We described earlier two strategies to overcome this
      limitation: (1) generation of HSVTK mutants with improved GCV activation
      potential and (2) construction of a fusion protein encoding HSVTK and mouse
      guanylate kinase (MGMK), the second enzyme in the GCV activation pathway. As a
      means to further enhance GCV activation, two MGMK/HSVTK constructs containing the
      HSVTK mutants, mutant 30 and SR39, were generated and evaluated for their tumor
      and bystander killing effects in vitro and in vivo. One fusion mutant, MGMK/30,
      shows significant reduction in IC(50) values of approximately 12 500-fold, 100
      fold, and 125-fold compared with HSVTK, mutant 30 or MGMK/HSVTK, respectively. In
      vitro bystander analyses show that 5% of MGMK/30-expressing cells are sufficient
      to induce 75% of tumor cell killing. In an xenograft tumor model, MGMK/30
      displays the greatest inhibition of tumor growth at a GCV concentration (1 mg kg(
      1)) that has no effect on wild-type HSVTK-, MGMK/HSVTK-, or mutant 30-transfected
      cells. Another fusion construct, MGMK/SR39, sensitizes rat C6 glioma cells to GCV
      by 2500-fold or 25-fold compared with HSVTK or MGMK/HSVTK, respectively. In vitro
      analyses show similar IC(50) values between cells harboring SR39 and MGMK/SR39,
      although MGMK/SR39 seems to elicit stronger bystander killing effects in which 1%
      of MGMK/SR39-transfected cells result in 60% cell death. In a xenograft tumor
      model, despite observable tumor growth inhibition, no statistical significance in
      tumor volume was detected between mice harboring SR39- and MGMK/SR39-transfected
      cells when dosed with 1 mg kg(-1) GCV. However, at a lower dose of GCV (0.1 mg
      kg(-1)), MGMK/SR39 seems to have slightly greater tumor growth inhibition
      properties compared with SR39 (P< or =0.05). In vivo studies indicate that both
      mutant fusion proteins display substantial improvements in bystander killing in
      the presence of 1 mg kg(-1) GCV, even when only 5% of the tumor cells are
      transfected. Such fusion mutants with exceptional prodrug converting properties
      will allow administration of lower and non-myelosuppressive doses of GCV
      concomitant with improved tumor killing and as such are promising candidates for
      translational gene therapy studies.

PMID- 19763148
TI  - Learning immunology from the yellow fever vaccine: innate immunity to systems
      vaccinology.
AB  - Despite their great success, we understand little about how effective vaccines
      stimulate protective immune responses. Two recent developments promise to yield
      such understanding: the appreciation of the crucial role of the innate immune
      system in sensing microorganisms and tuning immune responses, and advances in
      systems biology. Here I review how these developments are yielding insights into
      the mechanism of action of the yellow fever vaccine, one of the most successful
      vaccines ever developed, and the broader implications for vaccinology.

PMID- 19763149
TI  - Skin immune sentinels in health and disease.
AB  - Human skin and its immune cells provide essential protection of the human body
      from injury and infection. Recent studies reinforce the importance of
      keratinocytes as sensors of danger through alert systems such as the
      inflammasome. In addition, newly identified CD103(+) dendritic cells are
      strategically positioned for cross-presentation of skin-tropic pathogens and
      accumulating data highlight a key role of tissue-resident rather than circulating
      T cells in skin homeostasis and pathology. This Review focuses on recent progress
      in dissecting the functional role of skin immune cells in skin disease.

PMID- 19763150
TI  - The expansion of newborn screening: is reproductive benefit an appropriate
      pursuit?

PMID- 19763151
TI  - Bayesian statistical methods for genetic association studies.
AB  - Bayesian statistical methods have recently made great inroads into many areas of
      science, and this advance is now extending to the assessment of association
      between genetic variants and disease or other phenotypes. We review these
      methods, focusing on single-SNP tests in genome-wide association studies. We
      discuss the advantages of the Bayesian approach over classical (frequentist)
      approaches in this setting and provide a tutorial on basic analysis steps,
      including practical guidelines for appropriate prior specification. We
      demonstrate the use of Bayesian methods for fine mapping in candidate regions,
      discuss meta-analyses and provide guidance for refereeing manuscripts that
      contain Bayesian analyses.

PMID- 19763152
TI  - The impact of retrotransposons on human genome evolution.
AB  - Their ability to move within genomes gives transposable elements an intrinsic
      propensity to affect genome evolution. Non-long terminal repeat (LTR)
      retrotransposons--including LINE-1, Alu and SVA elements--have proliferated over
      the past 80 million years of primate evolution and now account for approximately
      one-third of the human genome. In this Review, we focus on this major class of
      elements and discuss the many ways that they affect the human genome: from
      generating insertion mutations and genomic instability to altering gene
      expression and contributing to genetic innovation. Increasingly detailed analyses
      of human and other primate genomes are revealing the scale and complexity of the
      past and current contributions of non-LTR retrotransposons to genomic change in
      the human lineage.

PMID- 19763153
TI  - Causes and consequences of microRNA dysregulation in cancer.
AB  - Over the past several years it has become clear that alterations in the
      expression of microRNA (miRNA) genes contribute to the pathogenesis of most--if
      not all--human malignancies. These alterations can be caused by various
      mechanisms, including deletions, amplifications or mutations involving miRNA
      loci, epigenetic silencing or the dysregulation of transcription factors that
      target specific miRNAs. Because malignant cells show dependence on the
      dysregulated expression of miRNA genes, which in turn control or are controlled
      by the dysregulation of multiple protein-coding oncogenes or tumour suppressor
      genes, these small RNAs provide important opportunities for the development of
      future miRNA-based therapies.

PMID- 19763154
TI  - The evolutionary consequences of erroneous protein synthesis.
AB  - Errors in protein synthesis disrupt cellular fitness, cause disease phenotypes
      and shape gene and genome evolution. Experimental and theoretical results on this
      topic have accumulated rapidly in disparate fields, such as neurobiology, protein
      biosynthesis and degradation and molecular evolution, but with limited
      communication among disciplines. Here, we review studies of error frequencies,
      the cellular and organismal consequences of errors and the attendant long-range
      evolutionary responses to errors. We emphasize major areas in which little is
      known, such as the failure rates of protein folding, in addition to areas in
      which technological innovations may enable imminent gains, such as the
      elucidation of translational missense error frequencies. Evolutionary responses
      to errors fall into two broad categories: adaptations that minimize errors and
      their attendant costs and adaptations that exploit errors for the organism's
      benefit.

PMID- 19763156
TI  - Non-invasive prenatal diagnosis: an ethical imperative.

PMID- 19763157
TI  - Synthesis and Characterization of Elastin-Mimetic Hybrid Polymers with
      Multiblock, Alternating Molecular Architecture and Elastomeric Properties.
AB  - We are interested in developing elastin-mimetic hybrid polymers (EMHPs) that
      capture the multiblock molecular architecture of tropoelastin as well as the
      remarkable elasticity of mature elastin. In this study, multiblock EMHPs
      containing flexible synthetic segments based on poly(ethylene glycol) (PEG)
      alternating with alanine-rich, lysine-containing peptides were synthesized by
      step-growth polymerization using alpha,omega-azido-PEG and alkyne-terminated
      AKA(3)KA (K = lysine, A = alanine) peptide, employing orthogonal click chemistry.
      The resulting EMHPs contain an estimated three to five repeats of PEG and
      AKA(3)KA and have an average molecular weight of 34 kDa. While the peptide alone
      exhibited alpha-helical structures at high pH, the fractional helicity for EMHPs
      was reduced. Covalent cross-linking of EMHPs with hexamethylene diisocyanate
      (HMDI) through the lysine residue in the peptide domain afforded an elastomeric
      hydrogel (xEMHP) with a compressive modulus of 0.12 MPa when hydrated. The
      mechanical properties of xEMHP are comparable to a commercial polyurethane
      elastomer (Tecoflex SG80A) under the same conditions. In vitro toxicity studies
      showed that while the soluble EMHPs inhibited the growth of primary porcine vocal
      fold fibroblasts (PVFFs) at concentrations >=0.2 mg/mL, the cross-linked hybrid
      elastomers did not leach out any toxic reagents and allowed PVFFs to grow and
      proliferate normally. The hybrid and modular approach provides a new strategy for
      developing elastomeric scaffolds for tissue engineering.

PMID- 19763158
TI  - Xpf and not the Fanconi anaemia proteins or Rev3 accounts for the extreme
      resistance to cisplatin in Dictyostelium discoideum.
AB  - Organisms like Dictyostelium discoideum, often referred to as DNA damage
      "extremophiles", can survive exposure to extremely high doses of radiation and
      DNA crosslinking agents. These agents form highly toxic DNA crosslinks that cause
      extensive DNA damage. However, little is known about how Dictyostelium and the
      other "extremophiles" can tolerate and repair such large numbers of DNA
      crosslinks. Here we describe a comprehensive genetic analysis of crosslink repair
      in Dictyostelium discoideum. We analyse three gene groups that are crucial for a
      replication-coupled repair process that removes DNA crosslinks in higher eukarya:
      The Fanconi anaemia pathway (FA), translesion synthesis (TLS), and nucleotide
      excision repair. Gene disruption studies unexpectedly reveal that the FA genes
      and the TLS enzyme Rev3 play minor roles in tolerance to crosslinks in
      Dictyostelium. However, disruption of the Xpf nuclease subcomponent results in
      striking hypersensitivity to crosslinks. Genetic interaction studies reveal that
      although Xpf functions with FA and TLS gene products, most Xpf mediated repair is
      independent of these two gene groups. These results suggest that Dictyostelium
      utilises a distinct Xpf nuclease-mediated repair process to remove crosslinked
      DNA. Other DNA damage-resistant organisms and chemoresistant cancer cells might
      adopt a similar strategy to develop resistance to DNA crosslinking agents.

PMID- 19763159
TI  - Human miRNA precursors with box H/ACA snoRNA features.
AB  - MicroRNAs (miRNAs) and small nucleolar RNAs (snoRNAs) are two classes of small
      non-coding regulatory RNAs, which have been much investigated in recent years.
      While their respective functions in the cell are distinct, they share interesting
      genomic similarities, and recent sequencing projects have identified processed
      forms of snoRNAs that resemble miRNAs. Here, we investigate a possible
      evolutionary relationship between miRNAs and box H/ACA snoRNAs. A comparison of
      the genomic locations of reported miRNAs and snoRNAs reveals an overlap of
      specific members of these classes. To test the hypothesis that some miRNAs might
      have evolved from snoRNA encoding genomic regions, reported miRNA-encoding
      regions were scanned for the presence of box H/ACA snoRNA features. Twenty miRNA
      precursors show significant similarity to H/ACA snoRNAs as predicted by snoGPS.
      These include molecules predicted to target known ribosomal RNA pseudouridylation
      sites in vivo for which no guide snoRNA has yet been reported. The predicted
      folded structures of these twenty H/ACA snoRNA-like miRNA precursors reveal
      molecules which resemble the structures of known box H/ACA snoRNAs. The genomic
      regions surrounding these predicted snoRNA-like miRNAs are often similar to
      regions around snoRNA retroposons, including the presence of transposable
      elements, target site duplications and poly (A) tails. We further show that the
      precursors of five H/ACA snoRNA-like miRNAs (miR-151, miR-605, mir-664, miR-215
      and miR-140) bind to dyskerin, a specific protein component of functional box
      H/ACA small nucleolar ribonucleoprotein complexes suggesting that these molecules
      have retained some H/ACA snoRNA functionality. The detection of small RNA
      molecules that share features of miRNAs and snoRNAs suggest that these classes of
      RNA may have an evolutionary relationship.

PMID- 19763160
TI  - Genetic analysis of variation in human meiotic recombination.
AB  - The number of recombination events per meiosis varies extensively among
      individuals. This recombination phenotype differs between female and male, and
      also among individuals of each gender. In this study, we used high-density SNP
      genotypes of over 2,300 individuals and their offspring in two datasets to
      characterize recombination landscape and to map the genetic variants that
      contribute to variation in recombination phenotypes. We found six genetic loci
      that are associated with recombination phenotypes. Two of these (RNF212 and an
      inversion on chromosome 17q21.31) were previously reported in the Icelandic
      population, and this is the first replication in any other population. Of the
      four newly identified loci (KIAA1462, PDZK1, UGCG, NUB1), results from expression
      studies provide support for their roles in meiosis. Each of the variants that we
      identified explains only a small fraction of the individual variation in
      recombination. Notably, we found different sequence variants associated with
      female and male recombination phenotypes, suggesting that they are regulated by
      different genes. Characterization of genetic variants that influence natural
      variation in meiotic recombination will lead to a better understanding of normal
      meiotic events as well as of non-disjunction, the primary cause of pregnancy
      loss.

PMID- 19763161
TI  - A role of SCN9A in human epilepsies, as a cause of febrile seizures and as a
      potential modifier of Dravet syndrome.
AB  - A follow-up study of a large Utah family with significant linkage to chromosome
      2q24 led us to identify a new febrile seizure (FS) gene, SCN9A encoding Na(v)1.7.
      In 21 affected members, we uncovered a potential mutation in a highly conserved
      amino acid, p.N641Y, in the large cytoplasmic loop between transmembrane domains
      I and II that was absent from 586 ethnically matched population control
      chromosomes. To establish a functional role for this mutation in seizure
      susceptibility, we introduced the orthologous mutation into the murine Scn9a
      ortholog using targeted homologous recombination. Compared to wild-type mice,
      homozygous Scn9a(N641Y/N641Y) knockin mice exhibit significantly reduced
      thresholds to electrically induced clonic and tonic-clonic seizures, and
      increased corneal kindling acquisition rates. Together, these data strongly
      support the SCN9A p.N641Y mutation as disease-causing in this family. To confirm
      the role of SCN9A in FS, we analyzed a collection of 92 unrelated FS patients and
      identified additional highly conserved Na(v)1.7 missense variants in 5% of the
      patients. After one of these children with FS later developed Dravet syndrome
      (severe myoclonic epilepsy of infancy), we sequenced the SCN1A gene, a gene known
      to be associated with Dravet syndrome, and identified a heterozygous frameshift
      mutation. Subsequent analysis of 109 Dravet syndrome patients yielded nine
      Na(v)1.7 missense variants (8% of the patients), all in highly conserved amino
      acids. Six of these Dravet syndrome patients with SCN9A missense variants also
      harbored either missense or splice site SCN1A mutations and three had no SCN1A
      mutations. This study provides evidence for a role of SCN9A in human epilepsies,
      both as a cause of FS and as a partner with SCN1A mutations.

PMID- 19763163
TI  - Identification of a cardiac disease modifier gene using forward genetics in the
      mouse.

PMID- 19763162
TI  - Multiple organ system defects and transcriptional dysregulation in the Nipbl(+/-)
      mouse, a model of Cornelia de Lange Syndrome.
AB  - Cornelia de Lange Syndrome (CdLS) is a multi-organ system birth defects disorder
      linked, in at least half of cases, to heterozygous mutations in the NIPBL gene.
      In animals and fungi, orthologs of NIPBL regulate cohesin, a complex of proteins
      that is essential for chromosome cohesion and is also implicated in DNA repair
      and transcriptional regulation. Mice heterozygous for a gene-trap mutation in
      Nipbl were produced and exhibited defects characteristic of CdLS, including small
      size, craniofacial anomalies, microbrachycephaly, heart defects, hearing
      abnormalities, delayed bone maturation, reduced body fat, behavioral
      disturbances, and high mortality (75-80%) during the first weeks of life. These
      phenotypes arose despite a decrease in Nipbl transcript levels of only
      approximately 30%, implying extreme sensitivity of development to small changes
      in Nipbl activity. Gene expression profiling demonstrated that Nipbl deficiency
      leads to modest but significant transcriptional dysregulation of many genes.
      Expression changes at the protocadherin beta (Pcdhb) locus, as well as at other
      loci, support the view that NIPBL influences long-range chromosomal regulatory
      interactions. In addition, evidence is presented that reduced expression of genes
      involved in adipogenic differentiation may underlie the low amounts of body fat
      observed both in Nipbl+/- mice and in individuals with CdLS.

PMID- 19763164
TI  - Redundant and specific roles of the ARGONAUTE proteins AGO1 and ZLL in
      development and small RNA-directed gene silencing.
AB  - The Arabidopsis ARGONAUTE1 (AGO1) and ZWILLE/PINHEAD/AGO10 (ZLL) proteins act in
      the miRNA and siRNA pathways and are essential for multiple processes in
      development. Here, we analyze what determines common and specific function of
      both proteins. Analysis of ago1 mutants with partially compromised AGO1 activity
      revealed that loss of ZLL function re-establishes both siRNA and miRNA pathways
      for a subset of AGO1 target genes. Loss of ZLL function in ago1 mutants led to
      increased AGO1 protein levels, whereas AGO1 mRNA levels were unchanged,
      implicating ZLL as a negative regulator of AGO1 at the protein level. Since ZLL,
      unlike AGO1, is not subjected to small RNA-mediated repression itself, this cross
      regulation has the potential to adjust RNA silencing activity independent of
      feedback dynamics. Although AGO1 is expressed in a broader pattern than ZLL,
      expression of AGO1 from the ZLL promoter restored transgene PTGS and most
      developmental defects of ago1, whereas ZLL rescued only a few AGO1 functions when
      expressed from the AGO1 promoter, suggesting that the specific functions of AGO1
      and ZLL are mainly determined by their protein sequence. Protein domain swapping
      experiments revealed that the PAZ domain, which in AGO1 is involved in binding
      small RNAs, is interchangeable between both proteins, suggesting that this common
      small RNA-binding domain contributes to redundant functions. By contrast, the
      conserved MID and PIWI domains, which are involved in 5'-end small RNA
      selectivity and mRNA cleavage, and the non-conserved N-terminal domain, to which
      no function has been assigned, provide specificity to AGO1 and ZLL protein
      function.

PMID- 19763165
TI  - Tnni3k modifies disease progression in murine models of cardiomyopathy.
AB  - The Calsequestrin (Csq) transgenic mouse model of cardiomyopathy exhibits wide
      variation in phenotypic progression dependent on genetic background. Seven heart
      failure modifier (Hrtfm) loci modify disease progression and outcome. Here we
      report Tnni3k (cardiac Troponin I-interacting kinase) as the gene underlying
      Hrtfm2. Strains with the more susceptible phenotype exhibit high transcript
      levels while less susceptible strains show dramatically reduced transcript
      levels. This decrease is caused by an intronic SNP in low-transcript strains that
      activates a cryptic splice site leading to a frameshifted transcript, followed by
      nonsense-mediated decay of message and an absence of detectable protein. A
      transgenic animal overexpressing human TNNI3K alone exhibits no cardiac
      phenotype. However, TNNI3K/Csq double transgenics display severely impaired
      systolic function and reduced survival, indicating that TNNI3K expression
      modifies disease progression. TNNI3K expression also accelerates disease
      progression in a pressure-overload model of heart failure. These combined data
      demonstrate that Tnni3k plays a critical role in the modulation of different
      forms of heart disease, and this protein may provide a novel target for
      therapeutic intervention.

PMID- 19763166
TI  - Noise management by molecular networks.
AB  - Fluctuations in the copy number of key regulatory macromolecules ("noise") may
      cause physiological heterogeneity in populations of (isogenic) cells. The
      kinetics of processes and their wiring in molecular networks can modulate this
      molecular noise. Here we present a theoretical framework to study the principles
      of noise management by the molecular networks in living cells. The theory makes
      use of the natural, hierarchical organization of those networks and makes their
      noise management more understandable in terms of network structure. Principles
      governing noise management by ultrasensitive systems, signaling cascades, gene
      networks and feedback circuitry are discovered using this approach. For a few
      frequently occurring network motifs we show how they manage noise. We derive
      simple and intuitive equations for noise in molecule copy numbers as a
      determinant of physiological heterogeneity. We show how noise levels and signal
      sensitivity can be set independently in molecular networks, but often changes in
      signal sensitivity affect noise propagation. Using theory and simulations, we
      show that negative feedback can both enhance and reduce noise. We identify a
      trade-off; noise reduction in one molecular intermediate by negative feedback is
      at the expense of increased noise in the levels of other molecules along the
      feedback loop. The reactants of the processes that are strongly (cooperatively)
      regulated, so as to allow for negative feedback with a high strength, will
      display enhanced noise.

PMID- 19763167
TI  - Estimating the continuous-time dynamics of energy and fat metabolism in mice.
AB  - The mouse has become the most popular organism for investigating molecular
      mechanisms of body weight regulation. But understanding the physiological context
      by which a molecule exerts its effect on body weight requires knowledge of energy
      intake, energy expenditure, and fuel selection. Furthermore, measurements of
      these variables made at an isolated time point cannot explain why body weight has
      its present value since body weight is determined by the past history of energy
      and macronutrient imbalance. While food intake and body weight changes can be
      frequently measured over several weeks (the relevant time scale for mice),
      correspondingly frequent measurements of energy expenditure and fuel selection
      are not currently feasible. To address this issue, we developed a mathematical
      method based on the law of energy conservation that uses the measured time course
      of body weight and food intake to estimate the underlying continuous-time
      dynamics of energy output and net fat oxidation. We applied our methodology to
      male C57BL/6 mice consuming various ad libitum diets during weight gain and loss
      over several weeks and present the first continuous-time estimates of energy
      output and net fat oxidation rates underlying the observed body composition
      changes. We show that transient energy and fat imbalances in the first several
      days following a diet switch can account for a significant fraction of the total
      body weight change. We also discovered a time-invariant curve relating body fat
      and fat-free masses in male C57BL/6 mice, and the shape of this curve determines
      how diet, fuel selection, and body composition are interrelated.

PMID- 19763168
TI  - Global analysis of extracytoplasmic stress signaling in Escherichia coli.
AB  - The Bae, Cpx, Psp, Rcs, and sigma(E) pathways constitute the Escherichia coli
      signaling systems that detect and respond to alterations of the bacterial
      envelope. Contributions of these systems to stress response have previously been
      examined individually; however, the possible interconnections between these
      pathways are unknown. Here we investigate the dynamics between the five stress
      response pathways by determining the specificities of each system with respect to
      signal-inducing conditions, and monitoring global transcriptional changes in
      response to transient overexpression of each of the effectors. Our studies show
      that different extracytoplasmic stress conditions elicit a combined response of
      these pathways. Involvement of the five pathways in the various tested stress
      conditions is explained by our unexpected finding that transcriptional responses
      induced by the individual systems show little overlap. The extracytoplasmic
      stress signaling pathways in E. coli thus regulate mainly complementary functions
      whose discrete contributions are integrated to mount the full adaptive response.

PMID- 19763169
TI  - Fast growth increases the selective advantage of a mutation arising recurrently
      during evolution under metal limitation.
AB  - Understanding the evolution of biological systems requires untangling the
      molecular mechanisms that connect genetic and environmental variations to their
      physiological consequences. Metal limitation across many environments, ranging
      from pathogens in the human body to phytoplankton in the oceans, imposes strong
      selection for improved metal acquisition systems. In this study, we uncovered the
      genetic and physiological basis of adaptation to metal limitation using
      experimental populations of Methylobacterium extorquens AM1 evolved in metal
      deficient growth media. We identified a transposition mutation arising
      recurrently in 30 of 32 independent populations that utilized methanol as a
      carbon source, but not in any of the 8 that utilized only succinate. These
      parallel insertion events increased expression of a novel transporter system that
      enhanced cobalt uptake. Such ability ensured the production of vitamin B(12), a
      cobalt-containing cofactor, to sustain two vitamin B(12)-dependent enzymatic
      reactions essential to methanol, but not succinate, metabolism. Interestingly,
      this mutation provided higher selective advantages under genetic backgrounds or
      incubation temperatures that permit faster growth, indicating growth-rate
      dependent epistatic and genotype-by-environment interactions. Our results link
      beneficial mutations emerging in a metal-limiting environment to their
      physiological basis in carbon metabolism, suggest that certain molecular features
      may promote the emergence of parallel mutations, and indicate that the selective
      advantages of some mutations depend generically upon changes in growth rate that
      can stem from either genetic or environmental influences.

PMID- 19763170
TI  - RAD50 is required for efficient initiation of resection and recombinational
      repair at random, gamma-induced double-strand break ends.
AB  - Resection of DNA double-strand break (DSB) ends is generally considered a
      critical determinant in pathways of DSB repair and genome stability. Unlike for
      enzymatically induced site-specific DSBs, little is known about processing of
      random "dirty-ended" DSBs created by DNA damaging agents such as ionizing
      radiation. Here we present a novel system for monitoring early events in the
      repair of random DSBs, based on our finding that single-strand tails generated by
      resection at the ends of large molecules in budding yeast decreases mobility
      during pulsed field gel electrophoresis (PFGE). We utilized this "PFGE-shift" to
      follow the fate of both ends of linear molecules generated by a single random DSB
      in circular chromosomes. Within 10 min after gamma-irradiation of G2/M arrested
      WT cells, there is a near-synchronous PFGE-shift of the linearized circular
      molecules, corresponding to resection of a few hundred bases. Resection at the
      radiation-induced DSBs continues so that by the time of significant repair of
      DSBs at 1 hr there is about 1-2 kb resection per DSB end. The PFGE-shift is
      comparable in WT and recombination-defective rad52 and rad51 strains but somewhat
      delayed in exo1 mutants. However, in rad50 and mre11 null mutants the initiation
      and generation of resected ends at radiation-induced DSB ends is greatly reduced
      in G2/M. Thus, the Rad50/Mre11/Xrs2 complex is responsible for rapid processing
      of most damaged ends into substrates that subsequently undergo recombinational
      repair. A similar requirement was found for RAD50 in asynchronously growing
      cells. Among the few molecules exhibiting shift in the rad50 mutant, the residual
      resection is consistent with resection at only one of the DSB ends. Surprisingly,
      within 1 hr after irradiation, double-length linear molecules are detected in the
      WT and rad50, but not in rad52, strains that are likely due to crossovers that
      are largely resection- and RAD50-independent.

PMID- 19763171
TI  - Predicting the evolution of sex on complex fitness landscapes.
AB  - Most population genetic theories on the evolution of sex or recombination are
      based on fairly restrictive assumptions about the nature of the underlying
      fitness landscapes. Here we use computer simulations to study the evolution of
      sex on fitness landscapes with different degrees of complexity and epistasis. We
      evaluate predictors of the evolution of sex, which are derived from the
      conditions established in the population genetic literature for the evolution of
      sex on simpler fitness landscapes. These predictors are based on quantities such
      as the variance of Hamming distance, mean fitness, additive genetic variance, and
      epistasis. We show that for complex fitness landscapes all the predictors
      generally perform poorly. Interestingly, while the simplest predictor, Delta
      Var(HD), also suffers from a lack of accuracy, it turns out to be the most robust
      across different types of fitness landscapes. Delta Var(HD) is based on the
      change in Hamming distance variance induced by recombination and thus does not
      require individual fitness measurements. The presence of loci that are not under
      selection can, however, severely diminish predictor accuracy. Our study thus
      highlights the difficulty of establishing reliable criteria for the evolution of
      sex on complex fitness landscapes and illustrates the challenge for both
      theoretical and experimental research on the origin and maintenance of sexual
      reproduction.

PMID- 19763172
TI  - A statistical model to identify differentially expressed proteins in 2D PAGE
      gels.
AB  - Two dimensional polyacrylamide gel electrophoresis (2D PAGE) is used to identify
      differentially expressed proteins and may be applied to biomarker discovery. A
      limitation of this approach is the inability to detect a protein when its
      concentration falls below the limit of detection. Consequently, differential
      expression of proteins may be missed when the level of a protein in the cases or
      controls is below the limit of detection for 2D PAGE. Standard statistical
      techniques have difficulty dealing with undetected proteins. To address this
      issue, we propose a mixture model that takes into account both detected and non
      detected proteins. Non-detected proteins are classified either as (a) proteins
      that are not expressed in at least one replicate, or (b) proteins that are
      expressed but are below the limit of detection. We obtain maximum likelihood
      estimates of the parameters of the mixture model, including the group-specific
      probability of expression and mean expression intensities. Differentially
      expressed proteins can be detected by using a Likelihood Ratio Test (LRT). Our
      simulation results, using data generated from biological experiments, show that
      the likelihood model has higher statistical power than standard statistical
      approaches to detect differentially expressed proteins. An R package, Slider
      (Statistical Likelihood model for Identifying Differential Expression in R), is
      freely available at http://www.cebl.auckland.ac.nz/slider.php.

PMID- 19763173
TI  - Nucleolar proteins suppress Caenorhabditis elegans innate immunity by inhibiting
      p53/CEP-1.
AB  - The tumor suppressor p53 has been implicated in multiple functions that play key
      roles in health and disease, including ribosome biogenesis, control of aging, and
      cell cycle regulation. A genetic screen for negative regulators of innate
      immunity in Caenorhabditis elegans led to the identification of a mutation in NOL
      6, a nucleolar RNA-associated protein (NRAP), which is involved in ribosome
      biogenesis and conserved across eukaryotic organisms. Mutation or silencing of
      NOL-6 and other nucleolar proteins results in an enhanced resistance to bacterial
      infections. A full-genome microarray analysis on animals with altered immune
      function due to mutation in nol-6 shows increased transcriptional levels of genes
      regulated by a p53 homologue, CEP-1. Further studies indicate that the activation
      of innate immunity by inhibition of nucleolar proteins requires p53/CEP-1 and its
      transcriptional target SYM-1. Since nucleoli and p53/CEP-1 are conserved, our
      results reveal an ancient immune mechanism by which the nucleolus may regulate
      immune responses against bacterial pathogens.

PMID- 19763174
TI  - Molecular tooth decay.

PMID- 19763175
TI  - Broad-scale recombination patterns underlying proper disjunction in humans.
AB  - Although recombination is essential to the successful completion of human
      meiosis, it remains unclear how tightly the process is regulated and over what
      scale. To assess the nature and stringency of constraints on human recombination,
      we examined crossover patterns in transmissions to viable, non-trisomic
      offspring, using dense genotyping data collected in a large set of pedigrees. Our
      analysis supports a requirement for one chiasma per chromosome rather than per
      arm to ensure proper disjunction, with additional chiasmata occurring in
      proportion to physical length. The requirement is not absolute, however, as
      chromosome 21 seems to be frequently transmitted properly in the absence of a
      chiasma in females, a finding that raises the possibility of a back-up mechanism
      aiding in its correct segregation. We also found a set of double crossovers in
      surprisingly close proximity, as expected from a second pathway that is not
      subject to crossover interference. These findings point to multiple mechanisms
      that shape the distribution of crossovers, influencing proper disjunction in
      humans.

PMID- 19763176
TI  - Segregating YKU80 and TLC1 alleles underlying natural variation in telomere
      properties in wild yeast.
AB  - In yeast, as in humans, telomere length varies among individuals and is
      controlled by multiple loci. In a quest to define the extent of variation in
      telomere length, we screened 112 wild-type Saccharomyces sensu stricto isolates.
      We found extensive telomere length variation in S. paradoxus isolates. This
      phenotype correlated with their geographic origin: European strains were observed
      to have extremely short telomeres (<150 bp), whereas American isolates had
      telomeres approximately three times as long (>400 bp). Insertions of a URA3 gene
      near telomeres allowed accurate analysis of individual telomere lengths and
      telomere position effect (TPE). Crossing the American and European strains
      resulted in F1 spores with a continuum of telomere lengths consistent with what
      would be predicted if many quantitative trait loci (QTLs) were involved in length
      maintenance. Variation in TPE is similarly quantitative but only weakly
      correlated with telomere length. Genotyping F1 segregants indicated several QTLs
      associated with telomere length and silencing variation. These QTLs include
      likely candidate genes but also map to regions where there are no known genes
      involved in telomeric properties. We detected transgressive segregation for both
      phenotypes. We validated by reciprocal hemizygosity that YKU80 and TLC1 are
      telomere-length QTLs in the two S. paradoxus subpopulations. Furthermore, we
      propose that sequence divergence within the Ku heterodimer generates negative
      epistasis within one of the allelic combinations (American-YKU70 and European
      YKU80) resulting in very short telomeres.

PMID- 19763177
TI  - A high throughput genetic screen identifies new early meiotic recombination
      functions in Arabidopsis thaliana.
AB  - Meiotic recombination is initiated by the formation of numerous DNA double-strand
      breaks (DSBs) catalysed by the widely conserved Spo11 protein. In Saccharomyces
      cerevisiae, Spo11 requires nine other proteins for meiotic DSB formation;
      however, unlike Spo11, few of these are conserved across kingdoms. In order to
      investigate this recombination step in higher eukaryotes, we took advantage of a
      high-throughput meiotic mutant screen carried out in the model plant Arabidopsis
      thaliana. A collection of 55,000 mutant lines was screened, and spo11-like
      mutations, characterised by a drastic decrease in chiasma formation at metaphase
      I associated with an absence of synapsis at prophase, were selected. This screen
      led to the identification of two populations of mutants classified according to
      their recombination defects: mutants that repair meiotic DSBs using the sister
      chromatid such as Atdmc1 or mutants that are unable to make DSBs like Atspo11-1.
      We found that in Arabidopsis thaliana at least four proteins are necessary for
      driving meiotic DSB repair via the homologous chromosomes. These include the
      previously characterised DMC1 and the Hop1-related ASY1 proteins, but also the
      meiotic specific cyclin SDS as well as the Hop2 Arabidopsis homologue AHP2.
      Analysing the mutants defective in DSB formation, we identified the previously
      characterised AtSPO11-1, AtSPO11-2, and AtPRD1 as well as two new genes, AtPRD2
      and AtPRD3. Our data thus increase the number of proteins necessary for DSB
      formation in Arabidopsis thaliana to five. Unlike SPO11 and (to a minor extent)
      PRD1, these two new proteins are poorly conserved among species, suggesting that
      the DSB formation mechanism, but not its regulation, is conserved among
      eukaryotes.

PMID- 19763178
TI  - Transcriptional profiling of the dose response: a more powerful approach for
      characterizing drug activities.
AB  - The dose response curve is the gold standard for measuring the effect of a drug
      treatment, but is rarely used in genomic scale transcriptional profiling due to
      perceived obstacles of cost and analysis. One barrier to examining
      transcriptional dose responses is that existing methods for microarray data
      analysis can identify patterns, but provide no quantitative pharmacological
      information. We developed analytical methods that identify transcripts responsive
      to dose, calculate classical pharmacological parameters such as the EC50, and
      enable an in-depth analysis of coordinated dose-dependent treatment effects. The
      approach was applied to a transcriptional profiling study that evaluated four
      kinase inhibitors (imatinib, nilotinib, dasatinib and PD0325901) across a six
      logarithm dose range, using 12 arrays per compound. The transcript responses
      proved a powerful means to characterize and compare the compounds: the
      distribution of EC50 values for the transcriptome was linked to specific targets,
      dose-dependent effects on cellular processes were identified using automated
      pathway analysis, and a connection was seen between EC50s in standard cellular
      assays and transcriptional EC50s. Our approach greatly enriches the information
      that can be obtained from standard transcriptional profiling technology.
      Moreover, these methods are automated, robust to non-optimized assays, and could
      be applied to other sources of quantitative data.

PMID- 19763179
TI  - Meiotic recombination in human oocytes.
AB  - Studies of human trisomies indicate a remarkable relationship between abnormal
      meiotic recombination and subsequent nondisjunction at maternal meiosis I or II.
      Specifically, failure to recombine or recombination events located either too
      near to or too far from the centromere have been linked to the origin of human
      trisomies. It should be possible to identify these abnormal crossover
      configurations by using immunofluorescence methodology to directly examine the
      meiotic recombination process in the human female. Accordingly, we initiated
      studies of crossover-associated proteins (e.g., MLH1) in human fetal oocytes to
      analyze their number and distribution on nondisjunction-prone human chromosomes
      and, more generally, to characterize genome-wide levels of recombination in the
      human female. Our analyses indicate that the number of MLH1 foci is lower than
      predicted from genetic linkage analysis, but its localization pattern conforms to
      that expected for a crossover-associated protein. In studies of individual
      chromosomes, our observations provide evidence for the presence of "vulnerable"
      crossover configurations in the fetal oocyte, consistent with the idea that these
      are subsequently translated into nondisjunctional events in the adult oocyte.

PMID- 19763180
TI  - Getting to grips with strangles: an effective multi-component recombinant vaccine
      for the protection of horses from Streptococcus equi infection.
AB  - Streptococcus equi subspecies equi (S. equi) is a clonal, equine host-adapted
      pathogen of global importance that causes a suppurative lymphodendopathy of the
      head and neck, more commonly known as Strangles. The disease is highly prevalent,
      can be severe and is highly contagious. Antibiotic treatment is usually
      ineffective. Live attenuated vaccine strains of S. equi have shown adverse
      reactions and they suffer from a short duration of immunity. Thus, a safe and
      effective vaccine against S. equi is highly desirable. The bacterium shows only
      limited genetic diversity and an effective vaccine could confer broad protection
      to horses throughout the world. Welsh mountain ponies (n = 7) vaccinated with a
      combination of seven recombinant S. equi proteins were significantly protected
      from experimental infection by S. equi, resembling the spontaneous disease.
      Vaccinated horses had significantly reduced incidence of lymph node swelling (p =
      0.0013) lymph node abscessation (p = 0.00001), fewer days of pyrexia (p =
      0.0001), reduced pathology scoring (p = 0.005) and lower bacterial recovery from
      lymph nodes (p = 0.004) when compared with non-vaccinated horses (n = 7). Six of
      7 vaccinated horses were protected whereas all 7 non-vaccinated became infected.
      The protective antigens consisted of five surface localized proteins and two IgG
      endopeptidases. A second vaccination trial (n = 7+7), in which the IgG
      endopeptidases were omitted, demonstrated only partial protection against S.
      equi, highlighting an important role for these vaccine components in establishing
      a protective immune response. S. equi shares >80% sequence identity with
      Streptococcus pyogenes. Several of the components utilized here have counterparts
      in S. pyogenes, suggesting that our findings have broader implications for the
      prevention of infection with this important human pathogen. This is one of only a
      few demonstrations of protection from streptococcal infection conferred by a
      recombinant multi-component subunit vaccine in a natural host.

PMID- 19763181
TI  - Early steps of HIV-1 fusion define the sensitivity to inhibitory peptides that
      block 6-helix bundle formation.
AB  - The HIV envelope (Env) glycoprotein mediates membrane fusion through sequential
      interactions with CD4 and coreceptors, followed by the refolding of the
      transmembrane gp41 subunit into the stable 6-helix bundle (6HB) conformation.
      Synthetic peptides derived from the gp41 C-terminal heptad repeat domain (C
      peptides) potently inhibit fusion by binding to the gp41 pre-bundle intermediates
      and blocking their conversion into the 6HB. Our recent work revealed that HIV-1
      enters cells by fusing with endosomes, but not with the plasma membrane. These
      studies also showed that, for the large part, gp41 pre-bundles progress toward
      6HBs in endosomal compartments and are thus protected from external fusion
      inhibitors. Here, we examined the consequences of endocytic entry on the gp41 pre
      bundle exposure and on the virus' sensitivity to C-peptides. The rates of CD4 and
      coreceptor binding, as well as the rate of productive receptor-mediated
      endocytosis, were measured by adding specific inhibitors of these steps at varied
      times of virus-cell incubation. Following the CD4 binding, CCR5-tropic viruses
      recruited a requisite number of coreceptors much faster than CXCR4-tropic
      viruses. The rate of subsequent uptake of ternary Env-CD4-coreceptor complexes
      did not correlate with the kinetics of coreceptor engagement. These measurements
      combined with kinetic analyses enabled the determination of the lifetime of pre
      bundle intermediates on the cell surface. Overall, these lifetimes correlated
      with the inhibitory potency of C-peptides. On the other hand, the basal
      sensitivity to peptides varied considerably among diverse HIV-1 isolates and
      ranked similarly with their susceptibility to inactivation by soluble CD4. We
      conclude that both the longevity of gp41 intermediates and the extent of
      irreversible conformational changes in Env upon CD4 binding determine the
      antiviral potency of C-peptides.

PMID- 19763182
TI  - A novel system for the launch of alphavirus RNA synthesis reveals a role for the
      Imd pathway in arthropod antiviral response.
AB  - Alphaviruses are RNA viruses transmitted between vertebrate hosts by arthropod
      vectors, primarily mosquitoes. How arthropods counteract alphaviruses or viruses
      per se is not very well understood. Drosophila melanogaster is a powerful model
      system for studying innate immunity against bacterial and fungal infections. In
      this study we report the use of a novel system to analyze replication of Sindbis
      virus (type species of the alphavirus genus) RNA following expression of a
      Sindbis virus replicon RNA from the fly genome. We demonstrate deficits in the
      immune deficiency (Imd) pathway enhance viral replication while mutations in the
      Toll pathway fail to affect replication. Similar results were observed with
      intrathoracic injections of whole virus and confirmed in cultured mosquito cells.
      These findings show that the Imd pathway mediates an antiviral response to
      Sindbis virus replication. To our knowledge, this is the first demonstration of
      an antiviral role for the Imd pathway in insects.

PMID- 19763183
TI  - Oxidative inactivation of mitochondrial aconitase results in iron and H2O2
      mediated neurotoxicity in rat primary mesencephalic cultures.
AB  - BACKGROUND: Mitochondrial oxidative stress is a contributing factor in the
      etiology of numerous neuronal disorders. However, the precise mechanism(s) by
      which mitochondrial reactive oxygen species (ROS) modify cellular targets to
      induce the death of neurons remains unknown. The goal of this study was to
      determine if oxidative inactivation of mitochondrial aconitase (m-aconitase)
      resulted in the release of redox-active iron (Fe2+) and hydrogen peroxide (H2O2)
      and whether this contributes to cell death. METHODOLOGY/PRINCIPAL FINDINGS:
      Incubation of rat primary mesencephalic cultures with the redox cycling herbicide
      paraquat (PQ2+) resulted in increased production of H2O2 and Fe2+ at times
      preceding cell death. To confirm the role of m-aconitase as a source of Fenton
      reagents and death, we overexpressed m-aconitase using an adenoviral construct
      thereby increasing the target available for inactivation by ROS. Co-labeling
      studies identified astrocytes as the predominant cell type expressing transduced
      m-aconitase although neurons were identified as the primary cell type dying.
      Oxidative inactivation of m-aconitase overexpressing cultures resulted in
      exacerbation of H2O2 production, Fe2+ accumulation and increased neuronal death.
      Increased cell death in m-aconitase overexpressing cultures was attenuated by
      addition of catalase and/or a cell permeable iron chelator suggesting that
      neuronal death occurred in part via astrocyte-derived H2O2. CONCLUSIONS: These
      results suggest a role of ROS-sensitive m-aconitase as a source of Fe2+ and H2O2
      and as a contributing factor to neurotoxicity.

PMID- 19763184
TI  - The Warburg effect is genetically determined in inherited pheochromocytomas.
AB  - The Warburg effect describes how cancer cells down-regulate their aerobic
      respiration and preferentially use glycolysis to generate energy. To evaluate the
      link between hypoxia and Warburg effect, we studied mitochondrial electron
      transport, angiogenesis and glycolysis in pheochromocytomas induced by germ-line
      mutations in VHL, RET, NF1 and SDH genes. SDH and VHL gene mutations have been
      shown to lead to the activation of hypoxic response, even in normoxic conditions,
      a process now referred to as pseudohypoxia. We observed a decrease in electron
      transport protein expression and activity, associated with increased angiogenesis
      in SDH- and VHL-related, pseudohypoxic tumors, while stimulation of glycolysis
      was solely observed in VHL tumors. Moreover, microarray analyses revealed that
      expression of genes involved in these metabolic pathways is an efficient tool for
      classification of pheochromocytomas in accordance with the predisposition gene
      mutated. Our data suggest an unexpected association between pseudohypoxia and
      loss of p53, which leads to a distinct Warburg effect in VHL-related
      pheochromocytomas.

PMID- 19763185
TI  - A Facile Synthesis of Carbamoylsilanes, -boranes and -phosphane Oxides -
      Isolation of the First Uncomplexed Carbamoylborane.
AB  - C-(Trimethylsilyloxy)-, C-(triisopropylsilyloxy)-, C-(diphenylboryloxy), C
      [bis(diisopropylamino)boryloxy]- and C-(di-tert-butylphosphoryloxy)-N,N
      diisopropylaldiminium salts are readily prepared in good to excellent yields from
      either diisopropylformamide or (chloromethylene)diisopropylammonium chloride.
      Deprotonation of these aldiminium salts leads to transient (amino)(oxy)carbenes,
      which cleanly rearrange to carbamoyl derivatives. This synthetic methodology
      gives access to sterically hindered carbamoylsilanes, -boranes and phosphane
      oxides that are hardly accessible by other routes.

PMID- 19763186
TI  - El Nino Southern Oscillation and vegetation dynamics as predictors of dengue
      fever cases in Costa Rica.
AB  - Dengue fever (DF) and dengue hemorrhagic fever (DHF) are growing health concerns
      throughout Latin America and the Caribbean. This study focuses on Costa Rica,
      which experienced over 100 000 cases of DF/DHF from 2003 to 2007. We utilized
      data on sea-surface temperature anomalies related to the El Nino Southern
      Oscillation (ENSO) and two vegetation indices derived from the Moderate
      Resolution Imaging Spectrometer (MODIS) from the Terra satellite to model the
      influence of climate and vegetation dynamics on DF/DHF cases in Costa Rica. Cross
      correlations were calculated to evaluate both positive and negative lag effects
      on the relationships between independent variables and DF/DHF cases. The model,
      which utilizes a sinusoid and non-linear least squares to fit case data, was able
      to explain 83% of the variance in weekly DF/DHF cases when independent variables
      were shifted backwards in time. When the independent variables were shifted
      forward in time, consistently with a forecasting approach, the model explained
      64% of the variance. Importantly, when five ENSO and two vegetation indices were
      included, the model reproduced a major DF/DHF epidemic of 2005. The unexplained
      variance in the model may be due to herd immunity and vector control measures,
      although information regarding these aspects of the disease system are generally
      lacking. Our analysis suggests that the model may be used to predict DF/DHF
      outbreaks as early as 40 weeks in advance and may also provide valuable
      information on the magnitude of future epidemics. In its current form it may be
      used to inform national vector control programs and policies regarding control
      measures; it is the first climate-based dengue model developed for this country
      and is potentially scalable to the broader region of Latin America and the
      Caribbean where dramatic increases in DF/DHF incidence and spread have been
      observed.

PMID- 19763187
TI  - Single-Molecule Spectroscopy of Semiconductor Nanocrystals on Plasmonic
      Nanostructures.
AB  - In the past several years we have demonstrated the metal-enhanced fluorescence
      (MEF) and the significant changes in the photophysical properties of fluorophores
      in the presence of metallic nanostructures and nanoparticles using ensemble
      spectroscopic studies. Here, in the present study, we explored the new insights
      of these interactions using single-molecule fluorescence spectroscopy. The single
      molecule study is expected to provide more information, especially on the
      heterogeneity in the fluorescence enhancement and decrease in lifetimes
      associated with fluorophore-metal interactions, which is otherwise not possible
      to observe using ensemble measurements. For the present study, we considered
      using CdTe nanocrystals (QDots) prepared using modified Weller method as the
      fluorophores under investigation. QDots having few nanometer sizes, tunable
      absorption and fluorescence spectral properties, and high photo-stabilities are
      of important class of fluorescent probes. Because of these unique features Qdots
      are widely used as probes in various fields, including biological labeling and
      imaging. These CdTe nanocrystals show characteristic spectral features in
      solution and on the solid substrate. The CdTe nanocrystals dispersed in PVA and
      spin-casted on SiFs surface show ~5-fold increase in fluorescence intensity and
      ~3-fold decrease in lifetimes compared to on glass substrate. The data obtained
      using ensemble and single molecule spectroscopy are complimentary to each other.
      Additionally as anticipated we have seen increased heterogeneity in the plasmon
      induced fluorescence modulations. Moreover single molecule spectroscopic study
      revealed significant reduction in blinking of CdTe nanocrystals on plasmonic
      nanostructures. Subsequently, we present these important findings on metal
      fluorophore interactions of CdTe nanocrystals (QDots) on plasmonic
      nanostructures.

PMID- 19763188
TI  - Decoding modulation of the neuromuscular transform.
AB  - When modulators of neuromuscular function alter the motor neuron spike patterns
      that elicit muscle contractions, it is predicted that they will also retune
      correspondingly the connecting processes of the neuromuscular transform. Here we
      confirm this prediction by analyzing data from the cardiac neuromuscular system
      of the blue crab. We apply a method that decodes the contraction response to the
      spike pattern in terms of three elementary building-block functions that
      completely characterize the neuromuscular transform. This method allows us to
      dissociate modulator-induced changes in the neuromuscular transform from changes
      in the spike pattern in the normally operating, essentially unperturbed
      neuromuscular system.

PMID- 19763189
TI  - Progress in the development of interpenetrating polymer network hydrogels.
AB  - Interpenetrating polymer networks (IPNs) have been the subject of extensive study
      since their advent in the 1960s. Hydrogel IPN systems have garnered significant
      attention in the last two decades due to their usefulness in biomedical
      applications. Of particular interest are the mechanical enhancements observed in
      "double network" IPN systems which exhibit nonlinear increases in fracture
      properties despite being composed of otherwise weak polymers. We have built upon
      pioneering work in this field as well as in responsive IPN systems to develop an
      IPN system based on end-linked poly-(ethylene glycol) (PEG) and loosely
      crosslinked poly(acrylic acid) (PAA) with hydrogen bond-reinforced strain
      hardening behavior in water and high initial Young's moduli under physiologic
      buffer conditions through osmotically induced pre-stress. Uniaxial tensile tests
      and equilibrium swelling measurements were used to study PEG/PAA IPN hydrogels
      having second networks prepared with varying crosslinking and photoinitiator
      content, pH, solids content, and comonomers. Studies involving the addition of
      non-ionic comonomers and neutralization of the second network showed that
      template polymerization appears to be important in the formation of mechanically
      enhanced IPNs.

PMID- 19763190
TI  - Fragmented QRS electrocardiogram--the hidden Talisman?

PMID- 19763191
TI  - Predicting successful pulmonary vein isolation in patients with atrial
      fibrillation by brain natriuretic Peptide plasma levels.
AB  - BACKGROUND: Catheter ablation for atrial fibrillation is a clinically established
      treatment by now while success rate varies between 60% and 85%. Interventional
      treatment of atrial fibrillation is still a challenging technique associated with
      a long procedure time and risk of major complications in up to 6 % of treated
      patients. The aim of this study was to investigate the predictive value of plasma
      brain natriuretic peptide (BNP) in patients undergoing pulmonary vein isolation
      concerning stable sinus rhythm after ablation. METHODS: In 68 consecutive
      patients with atrial fibrillation (AF) and normal left ventricular ejection
      fraction, BNP was measured at baseline before pulmonary vein isolation (PVI). All
      patients received a 7-days-holter monitoring 3 months after radiofrequency (RF)
      ablation in order to detect recurrent AF episodes. RESULTS: 48 patients with
      paroxysmal and 20 patients with persistent AF were enrolled. Baseline BNP was
      significantly higher in patients with persistent AF compared to patients with
      paroxysmal AF (145,5 pg/ml vs. 84,4 pg/ml; p<0,05). 3 months after PVI 38
      patients (79,1%) with paroxysmal AF had a stable sinus rhythm documented on 7
      days-holter monitoring, where as in 10 patients (20,9%) AF episodes were
      detected. Patients with a successful PVI showed significantly lower BNP plasma
      levels at baseline compared to patients with AF recurrrence (68,7 pg/ml vs. 144,1
      pg/ml; p<0,05). In patients with persistent AF 55% (11 cases) had no recurrence
      of AF at 3 months 7-days holter and in 9 patients (45%) AF recurred. BNP plasma
      levels at baseline were lower in patients with stable sinusrhythm after 3 months
      compared to the group of recurrent AF (105,8 pg/ml vs. 193,3 pg/ml; p=0,11).
      CONCLUSIONS: Patients with AF and low preprocedural BNP plasma levels showed a
      better outcome after PVI. Thus BNP may be helpful in patient selection for a
      successful treatment of AF by PVI.

PMID- 19763192
TI  - Use of a unique long pre-curved sheath to facilitate femoral placement of
      coronary sinus catheters.
AB  - METHODS: Catheterization of the coronary sinus (CS) from the femoral vein is
      widely used during electrophysiologic procedures. Access to the CS may be
      difficult. To address this problem we explored the utility of a long pre-formed
      (SAFL) sheath in a cohort of consecutive patients requiring CS cannulation in the
      electrophysiology laboratory. This unique sheath has distal curvatures in 2
      planes, potentially facilitating CS cannulation. RESULTS: 68 patients were
      studied with an average age of 63+/- 16 years. In twelve patients (18%), standard
      femoral CS cannulation was ineffective. In six of these patients, the SAFL sheath
      allowed for cannulation, and in six the subclavian approach was required. There
      were no significant differences in age, left ventricular ejection fraction, or
      echocardiographically estimated pulmonary artery systolic pressure between the
      various subgroups. There was a trend towards a larger left atrial size in the
      atrial flutter group (46mm+/- 7.9) versus all others (40.6mm+/- 6.3, P=.076).
      Left atrial size was 37 mm in the femoral sheath-requiring group versus 44 mm in
      all others (P=NS). CONCLUSION: Utilization of a unique commercially available
      long preformed sheath helps to provide femoral CS catheter access in selected
      cases in the electrophysiology laboratory.

PMID- 19763193
TI  - P wave duration and dispersion in patients with hyperthyroidism and the short
      term effects of antithyroid treatment.
AB  - BACKGROUND: Prolonged P wave duration and P wave dispersion (PWD) have been
      associated with an increased risk for atrial fibrillation (AF). Hyperthytodism is
      a frequent cause of atrial fibrillation (AF). METHODS: Forty-two patients with
      newly diagnosed overt hyperthyroidism and 20 healthy people were enrolled in the
      study. Transthoracic echocardiography, 12 lead surface ECG and thyroid hormone
      levels were studied at the time of enrollment and after achievement of euthyroid
      state with propylthiouracil treatment. RESULTS: Maximum P wave duration (Pmax)
      (97.4+/-14.6 vs. 84.2+/-9.5 msec, p<0.001), PWD (42.9+/-10.7 vs. 31.0+/-6.2 msec,
      p<0.001), deceleration (DT) (190.7+/-22.6 vs. 177.0+/-10.2 msec, p=0.013) and
      isovolumetric relaxation times (IVRT) (90.9+/-11.2 vs. 79.6+/-10.5 msec, p<0.001)
      were significantly higher in hyperthyroid patients compared to control group.
      Pmax and PWD were significantly correlated with the presence of hyperthyroidism.
      Pmax (97.4+/-14.6 to 84.3+/-8.6 msec, p<0,001) Pmin (54.1+/-8.6 to 48.1+/-8.5
      msec, p=0.002), PWD (42.9+/-10.7 to 35.9+/-8.1 msec, p=0.002) and DT (190.7+/
      22.6 to 185.5+/-18.3, p=0.036) were significantly decreased after achievement of
      euthyroid state in patients with hyperthyroidism. Diastolic dyfunction was seen
      in 5 patients at hyperthroid state but only in one patient at euthyroid state.
      CONCLUSIONS: Hyperthyroidism is associated with prolonged P wave duration and
      dispersion. Achievement of euthyroid state with propylthiouracil treatment
      results in shortening of P wave variables. Diastolic function may have a partial
      effect for the increased Pmax and PWD. Shortening of Pmax and PWD may be a marker
      for the prevention of AF with the anti-thyroid treatment.

PMID- 19763194
TI  - The use of oral ranolazine to convert new or paroxysmal atrial fibrillation: a
      review of experience with implications for possible "pill in the pocket" approach
      to atrial fibrillation.
AB  - BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia requiring
      treatment. High dose oral anti-arrhythmics may cardiovert some paroxysmal AF.
      This "pill in pocket" approach has allowed patients to treat themselves on an as
      needed basis. Pro-arrhythmic concerns have limited the usefulness of this
      approach to patients without structural heart disease. Ranolazine is an anti
      anginal agent, which inhibits abnormal late Na+ channel currents in
      cardiomyocytes and decreases sodium-calcium overload. Ranolazine is a potent
      inhibitor of after-depolarizations, which have been implicated in the initiation
      and propagation of AF. Because ranolazine has no known pro-arrhythmic effects, it
      could be useful as a safe "pill in the pocket" agent if it were effective in
      converting AF. We describe our experience using oral ranolazine to convert new or
      paroxysmal AF. METHODS: 2000 mg of ranolazine were administered to 18 patients
      with new (11 patients) or paroxysmal (7 patients) AF of at least 3, but not
      greater than 48 hours duration. Most patients (14) were in the hospital at the
      time ranolazine was administered. Age, sex, echocardiographic data, associated
      health conditions and structural heart disease were recorded. Successful
      conversion was defined as restoring sinus rhythm within 6 hours of ranolazine
      administration. RESULTS: All but 1 patient had some form of structural heart
      disease and all but 2 patients had left atrial enlargement. Thirteen of 18
      patients converted to sinus rhythm. No pro-arrhythmic effects, hemodynamic
      instability, adverse rate effects, or perceived intolerance (other than
      constipation) were noted. The 72% conversion rate was comparable to other
      reported "pill in the pocket" protocols. CONCLUSIONS: High dose oral ranolazine
      shows utility as a possible safe agent to convert new or paroxysmal AF. Lack of
      blinded controls and small numbers limits the power of this observation.

PMID- 19763195
TI  - ECG for the diagnosis of pulmonary embolism when conventional imaging cannot be
      utilized: a case report and review of the literature.
AB  - The diagnosis of acute pulmonary embolism has always been challenging. However,
      it has recently been greatly assisted through advances in radiological imaging.
      While imaging techniques are widely available, they cannot always be utilized. We
      report a case of acute pulmonary embolism in a patient with several prior
      pulmonary resections that would likely result in a non-diagnostic V/Q scan and
      acute renal insufficiency that was a relative contraindication to CT pulmonary
      angiography. The patient's electrocardiogram displayed several features
      suggestive of acute pulmonary embolism, which in the absence of effective
      radiological imaging, were essential in her diagnosis and management.

PMID- 19763196
TI  - A novel way of repair of insulation breaks during pacemaker generator
      replacement.
AB  - Minor abrasions can occur while mobilising old lead during pacemaker generator
      replacement necesittating placement of additional lead adding to the financial
      burden and junk in heart. We describe a novel way of repair of old pacemaker lead
      preventing additional lead placement.

PMID- 19763197
TI  - Radiofrequency catheter ablation of atrioventricular nodal reentrant tachycardia
      associated with anomalous drainage of both superior vena cava into coronary
      sinus.
AB  - Total upper body drainage via left superior vena cava into coronary sinus (i.e.
      absent right superior vena cava) is a rare anomaly and distorts the anatomy of
      coronary sinus and triangle of Koch. Herewith we are reporting the first report
      of ablation in a patient with superior vena cava draining into coronary sinus
      totally. This patient with atrioventricular nodal re-entrant tachycardia,
      baseline left bundle branch block, transient complete heart block during
      electrophysiological study and total upper body venous drainage into coronary
      sinus had successful slow pathway ablation using anatomical approach.

PMID- 19763198
TI  - Extremely prolonged ventricular asystole.
AB  - We are reporting an extremely prolonged sinus arrest documented by Holter
      monitoring.

PMID- 19763199
TI  - A two loop shoelace granny knot in the coronary sinus.

PMID- 19763200
TI  - An alternate explanation of pancreatitis in patients on atypical antipsychotic
      medications.

PMID- 19763201
TI  - Brain and behavior.

PMID- 19763202
TI  - Treatment of depression: an update on antidepressant monotherapy and combination
      therapy.
AB  - We analyzed the trends in product regimens used to treat depression to
      investigate whether there has been a shift in treatment patterns following the
      May 2008 launch of desvenalfaxine in the United States and the approval of an
      atypical antipsychotic as add-on therapy to antidepressants. Our analysis
      suggests that antidepressant monotherapy continues to be the most widely used
      drug treatment approach, accounting for 84 percent of depression treatment
      regimens. Antidepressant monotherapy is more prevalent among primary care
      physician-prescribed treatment regimens (92%) than psychiatry-prescribed regimens
      (73%). Combination treatment regimens have become increasingly more common as
      physician perception of disease severity increases, with antidepressant
      combination therapy accounting for eight percent, 17 percent, and 27 percent of
      treatment regimens for mild, moderate, and severe depression, respectively. The
      most commonly used agents in addition to an antidepressant in combination
      treatment regimens include another antidepressant (40% of combination regimens),
      an anxiety agent (40%), and/or atypical antipsychotics (18%). A trend analysis
      suggests that combination regimens that include an antidepressant plus an
      atypical antipsychotic, anxiety agent, or a prescription sleep aid comprise a
      greater share of combination regimens in 12 months ending May 2009 than they did
      in 12 months ending June 2008.

PMID- 19763203
TI  - When Granny Is the Wolf: Understanding and Approaching College-aged Female
      Victims of Acquaintance Rape.
AB  - College is generally felt to be an exciting time in the lives of young people;
      however, some college-aged students find themselves in difficult situations. For
      young women especially, acquaintance rape in the college years is a risk. While
      men can also be victims of sexual assault, it is far more common for women to be
      victimized. This article reviews the literature of acquaintance rape, including
      situational risk factors, perpetrator characteristics, and victim
      characteristics, as well as strategies to prevent revictimization, utilizing a
      female victim as the composite case.

PMID- 19763204
TI  - The use of duloxetine in chronic bulimia nervosa: a case report.
AB  - Selective serotonin reuptake inhibitors are routinely prescribed as off-label
      treatments for bulimia nervosa. There is, however, a paucity of literature
      addressing the efficacy of the serotonin norepinephrine reuptake inhibitors in
      the pharmacologic management of this disorder. This article describes a clinical
      situation in which duloxetine, a serotonin norepinephrine reuptake inhibitor,
      effectively treated a patient with long-standing bulimia nervosa, purging type,
      and comorbid generalized anxiety disorder.

PMID- 19763205
TI  - Misdiagnosed Bipolar Disorder Reveals Itself to be Posttraumatic Stress Disorder
      with Comorbid Pseudotumor Cerebri: A Case Report.
AB  - We present the case of a patient with a reported history of bipolar II and
      borderline personality disorders who presented to our inpatient psychiatry
      department following a suicidal gesture. We determined that she was not suffering
      from bipolar disorder at all, and we diagnosed her with posttraumatic stress
      disorder and pseudotumor cerebri. This paper describes the overlap of symptoms of
      bipolar disorder and posttraumatic stress disorder, which may lead to an
      incorrect diagnosis. Additionally, the patient had the complicating factor of
      comorbid pseudotumor cerebri, which we feel contributed to her psychiatric
      symptoms. Once the patient was properly diagnosed and placed on appropriate
      treatment, she responded well.

PMID- 19763206
TI  - Panic disorder subtypes: deceptive somatic impersonators.
AB  - Traditional panic attacks are characterized by multiple somatic symptoms
      involving the cardiac, respiratory, gastrointestinal, and vestibular systems.
      However, on occasion, panic disorder symptoms may congeal into one predominant
      system. These atypical presentations, in which symptoms manifest in a single
      system, are described as panic disorder subtypes. Four subtypes are commonly
      reported: 1) cardiac, 2) respiratory, 3) gastrointestinal, and 4) vestibular. In
      this edition of The Interface, we discuss how these subtypes may mimic organic
      diseases, leading to under-recognition, under-treatment, and over-utilization of
      healthcare resources.

PMID- 19763207
TI  - What puts a psychiatrist at risk for a malpractice lawsuit?
AB  - This ongoing column is dedicated to providing information to our readers on
      managing legal risks associated with medical practice. We invite questions from
      our readers. The answers are provided by PRMS, Inc. (www.prms.com), a manager of
      medical professional liability insurance programs with services that include risk
      management consultation, education and onsite risk management audits, and other
      resources to healthcare providers to help improve patient outcomes and reduce
      professional liability risk. The answers published in this column represent those
      of only one risk management consulting company. Other risk management consulting
      companies or insurance carriers may provide different advice, and readers should
      take this into consideration. The information in this column does not constitute
      legal advice. For legal advice, contact your personal attorney.

PMID- 19763208
TI  - One vs. Two Burr Hole Craniostomy in Surgical Treatment of Chronic Subdural
      Hematoma.
AB  - OBJECTIVE: Chronic subdural hematoma (CSDH) is one of the most common types of
      traumatic intracranial hemorrhage, usually occurring in the older patients, with
      a good surgical prognosis. Burr hole craniostomy is the most frequently used
      neurosurgical treatment of CSDH. However, there have been only few studies to
      assess the role of the number of burr holes in respect to recurrence rates. The
      aim of this study is to compare the postoperative recurrence rates between one
      and two burr craniostomy with closed-system drainage for CSDH. METHODS: From
      January 2002 to December 2006, 180 consecutive patients who were treated with
      burr hole craniostomy with closed-system drainage for the symptomatic CSDH were
      enrolled. Pre- and post-operative computed tomography (CT) scans and/or magnetic
      resonance imaging (MRI) were used for radiological evaluation. The number of burr
      hole was decided by neurosurgeon's preference and was usually made on the maximum
      width of hematoma. The patients were followed with clinical symptoms or signs and
      CT scans. All the drainage catheters were maintained below the head level and
      removed after CT scans showing satisfactory evacuation. All patients were
      followed-up for at least 1 month after discharge. RESULTS: Out of 180 patients,
      51 patients were treated with one burr hole, whereas 129 were treated with two
      burr holes. The overall postoperative recurrence rate was 5.6% (n = 10/180) in
      our study. One of 51 patients (2.0%) operated on with one burr hole recurred,
      whereas 9 of 129 patients (7.0%) evacuated by two burr holes recurred. Although
      the number of burr hole in this study is not statistically associated with
      postoperative recurrence rate (p > 0.05), CSDH treated with two burr holes showed
      somewhat higher recurrence rates. CONCLUSION: In agreement with previous studies,
      burr hole craniostomy with closed drainage achieved a good surgical prognosis as
      a treatment of CSDH in this study. Results of our study indicate that burr hole
      craniostomy with one burr hole would be sufficient to evacuate CSDH with lower
      recurrence rate.

PMID- 19763209
TI  - Seizures and Epilepsy following Aneurysmal Subarachnoid Hemorrhage : Incidence
      and Risk Factors.
AB  - OBJECTIVE: Although prophylactic antiepileptic drug (AED) use in patients with
      aneurysmal subarachnoid hemorrhage (SAH) is a common practice, lack of uniform
      definitions and guidelines for seizures and AEDs rendered this prescription more
      habitual instead of evidence-based manner. We herein evaluated the incidence and
      predictive factors of seizure and complications about AED use. METHODS: From July
      1999 to June 2007, data of a total of 547 patients with aneurysmal SAH who
      underwent operative treatments were reviewed. For these, the incidence and risk
      factors of seizures and epilepsy were assessed, in addition to complications of
      AEDs. RESULTS: Eighty-three patients (15.2%) had at least one seizure following
      SAH. Forty-three patients (7.9%) had onset seizures, 34 (6.2%) had perioperative
      seizures, and 17 (3.1%) had late epilepsy. Younger age (< 40 years), poor
      clinical grade, thick hemorrhage, acute hydrocephalus, and rebleeding were
      related to the occurrence of onset seizures. Cortical infarction and thick
      hemorrhage were independent risk factors for the occurrence of late epilepsy.
      Onset seizures were not predictive of late epilepsy. Moreover, adverse drug
      effects were identified in 128 patients (23.4%) with AEDs. CONCLUSION:
      Perioperative seizures are not significant predictors for late epilepsy. Instead,
      initial amount of SAH and surgery-induced cortical damage should be seriously
      considered as risk factors for late epilepsy. Because AEDs can not prevent early
      postoperative seizures (< 1 week) and potentially cause unexpected side effects,
      long-term use should be readjusted in high-risk patients.

PMID- 19763210
TI  - Cardiac troponin I elevation in patients with aneurysmal subarachnoid hemorrhage.
AB  - OBJECTIVE: Cardiac dysfunction after aneurysmal subarachnoid hemorrhage (SAH) is
      associated with elevation of serum cardiac troponin I (cTnI) levels. Elevation of
      cTnI predicts cardiopulmonary and neurological complications, and poor outcome.
      METHODS: We retrospectively reviewed the medical and radiologic records of 114
      (male : 30, female : 84) patients who developed aneurysmal SAH between January
      2006 and June 2007 and had no history of previous cardiac problems. We evaluated
      their electrocardiography and cTnI level, which had been measured at admission. A
      cTnI level above 0.5 microg/L was defined as an indicator of cardiac injury
      following SAH. We examined various clinical factors for their association with
      cTnI elevation and analyzed data using chi-square test, t-test and logistic
      regression test with SPSS version 12.0. The results were considered significant
      at p < 0.05. RESULTS: THE FOLLOWING PARAMETERS SHOWS A CORRELATION WITH CTNI
      ELEVATION : higher Hunt-Hess (H-H) grade (p = 0.000), poor Glasgow Outcome Scale
      (GOS) score (p = 0.000), profound pulmonary complication (p = 0.043), higher
      heart rate during initial three days following SAH (p = 0.029), ruptured aneurysm
      on communicating segment of internal carotid artery (p = 0.025), incidence of
      vasospasm (p = 0.421), and duration of hyperdynamic therapy for vasospasm (p =
      0.292). A significant determinants for outcome were cTnI elevation (p = 0.046)
      and H-H grade (p = 0.000) in a multivariate study. CONCLUSION: A cTnI is a good
      indicator for cardiopulmonary and neurologic complications and outcome following
      SAH. Consideration of variable clinical factors that related with cTnI elevation
      may be useful tactics for treatment of SAH and concomitant complications.

PMID- 19763211
TI  - Microsurgical experience with supraorbital keyhole operations on anterior
      circulation aneurysms.
AB  - OBJECTIVE: Conventional pterional approach is a commonly used neurosurgical
      technique for the treatment of cerebral aneurysms. However, this technique
      requires more extensive brain exposure than other key hole approaches and is
      sometimes associated with surgical traumatization or cosmetic problems. The aim
      of this study was to compare the postoperative outcome between pterional and
      supraorbital keyhole approaches in the patients with anterior circulation
      aneurysms. METHODS: The authors reviewed patients with anterior circulation
      aneurysms who underwent aneurysm clipping via pterional or supraorbital keyhole
      approach at a single institute over a period of 2 years. Ninety-eight patients
      harboring 108 aneurysms were included in this study. Various outcomes were
      recorded, which included clinical grade, cosmetic problems, patients'
      satisfaction and complications such as chewing discomfort, frontal muscle
      weakness, hyposmia, infection. RESULTS: The supraorbital approach exhibited a
      shorter operation time compared with the pterional approach. Complications such
      as chewing discomfort occurred less frequently in the supraorbital approach
      group. Moreover, the cosmetic outcome was significantly better in the
      supraorbital group than in the pterional group. CONCLUSION: The supraorbital
      keyhole approach reduced intra- and postoperative complications, including
      chewing discomfort and cosmetic disturbances, compared with the conventional
      pterional approach.

PMID- 19763212
TI  - Even in patients with a small hemorrhagic volume, stereotactic-guided evacuation
      of spontaneous intracerebral hemorrhage improves functional outcome.
AB  - OBJECTIVE: The decision to adopt a conservative or surgical modality for a
      relatively small volume of spontaneous intracerebral hemorrhage (SICH) is
      difficult and often controversial, especially when consciousness is tolerable.
      The authors examined the results of stereotactic-guided evacuation of SICH for
      relatively small volumes with respect to functional outcome. METHODS: This
      prospective study was performed on 387 patients with SICH who underwent
      stereotactic-guided evacuation (n = 204, group A) or conservative treatment (n =
      183, group B) during the past 8 years. The primary end-point was recovery of
      functional status, which was estimated using the Modified Barthel Index (MBI) and
      the modified Rankin Scale (mRS). RESULTS: All patients had a Glasgow coma scale
      (GCS) score of >/= 13 and unilateral hemiparesis of less than motor power grade
      3. Group demographic characteristics and initial neurological statuses were
      similar. In all cases, the volume of SICH involved was < 30 cm(3) and location
      was limited to basal ganglia and thalamus. At 6-month follow-ups, MBI was 90.9 in
      group A and 62.4 in group B (p < 0.05), and MRS was 1.2 in group A and 3.0 in
      group B (p < 0.05). Better motor function and stereotactic-guided evacuation had
      a significant effect on a functional recovery in regression analyses. CONCLUSION:
      Even in patients with a small volume of SICH, stereotactic-guided evacuation
      improved functional recovery in activities in daily life than conservative
      treatment did.

PMID- 19763213
TI  - Multi-modality treatment for intracranial arteriovenous malformation associated
      with arterial aneurysm.
AB  - OBJECTIVE: Intracranial arteriovenous malformation (AVM) associated with aneurysm
      has been infrequently encountered and the treatment for this malady is
      challenging. We report here on our clinical experience with AVMs associated with
      arterial aneurysms that were managed by multimodality treatments, including
      clipping of the aneurysm, microsurgery, Gamma-knife radiosurgery (GKS) and
      Guglielmi detachable coil (GDC) embolization. METHODS: We reviewed the treatment
      plans, radiological findings and clinical courses of 21 patients who were treated
      with GKS for AVM associated with aneurysm. RESULTS: Twenty-seven aneurysms in 21
      patients with AVMs were enrolled in this study. Hemorrhage was the most frequent
      presenting symptom (17 patients : 80.9%). Bleeding was caused by an AVM nidus in
      11 cases, aneurysm rupture in 5 and an undetermined origin in 1. Five patients
      were treated for associated aneurysm with clipping followed by GKS for the AVM
      and 11 patients were treated with GDC embolization combined with GKS for an AVM.
      Although 11 associated aneurysms remained untreated after GKS, none of them
      ruptured and 4 aneurysms regressed during the follow up period. Two aneurysms
      increased in size despite the disappearance of the AVM nidus after GKS and then
      these aneurysms were treated with GDC embolization. CONCLUSION: If combined
      treatment using microsurgery, GKS and endovascular treatment can be adequately
      used for these patients, a better prognosis can be obtained. In particular, GKS
      and GDC embolization are considered to have significant roles to minimize
      neurologic injury.

PMID- 19763214
TI  - Incidence and risk factors of infection caused by vancomycin-resistant
      enterococcus colonization in neurosurgical intensive care unit patients.
AB  - OBJECTIVE: This study was aimed to identify the incidence and risk factors of
      vancomycin-resistant enterococcus (VRE) colonization in neurosurgical practice of
      field, with particular attention to intensive care unit (ICU). METHODS: This
      retrospective study was carried out on the Neurosurgical ICU (NICU), during the
      period from January. 2005 to December. 2007, in 414 consecutive patients who had
      been admitted to the NICU. Demographics and known risk factors were retrieved and
      assessed by statistical methods. RESULTS: A total of 52 patients had VRE
      colonization among 414 patients enrolled, with an overall prevalence rate of
      6.1%. E. faecium was the most frequently isolated pathogen, and 92.3% of all VRE
      were isolated from urine specimen. Active infection was noticed only in 2
      patients with bacteremia and meningitis. Relative antibiotic agents were third
      generation cephalosporin in 40%, and vancomycin in 23%, and multiple antibiotic
      usages were also identified in 13% of all cases. Multivariate analyses showed
      Glasgow coma scale (GCS) score less than 8, placement of Foley catheter longer
      than 2 weeks, ICU stay over 2 weeks and presence of nearby VRE-positive patients
      had a significantly independent association with VRE infection. CONCLUSION: When
      managing the high-risk patients being prone to be infected VRE in the NICU,
      extreme caution should be paid upon. Because prevention and outbreak control is
      of ultimate importance, clinicians should be alert the possibility of impending
      colonization and infection by all means available. The most crucial interventions
      are careful hand washing, strict glove handling, meticulous and active screening,
      and complete segregation.

PMID- 19763215
TI  - A morphometric aspect of the brachial plexus in the periclavicular region.
AB  - OBJECTIVE: The purpose of this study was to determine the normal morphometric
      landmarks of the uniting and dividing points of the brachial plexus (BP) in the
      periclavicular region to provide useful guidance in surgery of BP injuries.
      METHODS: A total of 20 brachial plexuses were obtained from 10 adult, formalin
      fixed cadavers. Distances were measured on the basis of the Chassaignac tubercle
      (CT), and the most lateral margin of the BP (LMBP) crossing the superior and
      inferior edge of the clavicle. RESULTS: LMBP was located within 25 mm medially
      from the midpoint in all subjects. In the supraclavicular region, the upper trunk
      uniting at 21 +/- 7 mm from the CT, separating into divisions at 42 +/- 5 mm from
      the CT, and dividing at 19 +/- 4 mm from the LMBP crossing the superior edge of
      the clavicle. In the infraclavicular region, the distance from the inferior edge
      of the clavicle to the musculocutaneous nerve (MCN) origin was 49 +/- 1 mm, to
      the median nerve origin 57 +/- 7 mm, and the ulnar nerve origin 48 +/- 6 mm. From
      the lateral margin of the pectoralis minor to the MCN origin the distance
      averaged 3.3 +/- 10 mm. Mean diameter of the MCN was 4.3 +/- 1.1 mm (range, 2.5
      6.0) in males (n = 6), and 3.1 +/- 1.5 mm (range, 1.6-4.0) in females (n = 4).
      CONCLUSION: We hope these data will aid in understanding the anatomy of the BP
      and in planning surgical treatment in BP injuries.

PMID- 19763216
TI  - Remote cerebellar hemorrhage complicated after supratentorial surgery:
      retrospective study with review of articles.
AB  - OBJECTIVE: Remote cerebellar hemorrhage (RCH) is one of the rare complications
      occurring after supratentorial surgery, and its pathomechanism is poorly
      understood. We report 10 cases of RCH from our institution and review 154 cases
      from a database in order to delineate incidence, common presentation, risk
      factors, and outcomes of this complication. In addition, the means of prevention
      are discussed. METHODS: We reviewed the medical records of 10 patients who
      experienced RCH after undergoing supratentorial surgery at our institution
      between 2001 and 2008. A database search in Medline revealed 154 cases of RCH in
      the English literature. Characteristic features were analyzed and compared.
      RESULTS: There were 10 cases of RCH among 3307 supratentorial surgery cases,
      indicating a 0.3% incidence. All patients had characteristic imaging features of
      RCH, namely a streaky bleeding pattern in the superior folia of the cerebellum.
      Seven patients had a history of preoperative hypertension. Four cases were
      related to cerebral aneurysms, and other four developed after the removal of
      brain tumors. Cerebrospinal fluid (CSF) drainage apparatuses were installed
      postoperatively in all cases. Outcomes according to modified Rankin scale (mRS)
      were good in 7 patients, with 1 fatal case. CONCLUSION: RCH is a rare
      complication after supratentorial surgery, and the exact etiology still remains
      uncertain. Hypertension and perioperative loss of CSF seem positively correlated
      with RCH, but no single risk factor is totally responsible. Patients with RCH
      should be closely observed to improve their prognosis.

PMID- 19763217
TI  - The Changes in Range of Motion after a Lumbar Spinal Arthroplasty with Charite in
      the Human Cadaveric Spine under Physiologic Compressive Follower Preload : A
      Comparative Study between Load Control Protocol and Hybrid Protocol.
AB  - OBJECTIVE: To compare two testing protocols for evaluating range of motion (ROM)
      changes in the preloaded cadaveric spines implanted with a mobile core type
      Charite lumbar artificial disc. METHODS: Using five human cadaveric lumbosacral
      spines (L2-S2), baseline ROMs were measured with a bending moment of 8 Nm for all
      motion modes (flexion/extension, lateral bending, and axial rotation) in intact
      spine. The ROM was tracked using a video-based motion-capturing system. After the
      Charite disc was implanted at the L4-L5 level, the measurement was repeated using
      two different methods : 1) loading up to 8 Nm with the compressive follower
      preload as in testing the intact spine (Load control protocol), 2) loading in
      displacement control until the total ROM of L2-S2 matches that when the intact
      spine was loaded under load control (Hybrid protocol). The comparison between the
      data of each protocol was performed. RESULTS: The ROMs of the L4-L5 arthroplasty
      level were increased in all test modalities (p < 0.05 in bending and rotation)
      under both load and hybrid protocols. At the adjacent segments, the ROMs were
      increased in all modes except flexion under load control protocol. Under hybrid
      protocol, the adjacent segments demonstrated decreased ROMs in all modalities
      except extension at the inferior segment. Statistical significance between load
      and hybrid protocols was observed during bending and rotation at the operative
      and adjacent levels (p < 0.05). CONCLUSION: In hybrid protocol, the Charite disc
      provided a relatively better restoration of ROM, than in the load control
      protocol, reproducing clinical observations in terms of motion following surgery.

PMID- 19763218
TI  - Intradural retroclival chordoma.
AB  - A 43-year-old woman presented with dizziness, ataxia and right hearing
      difficulty. Her magnetic resonance images demonstrated an inhomogeneously
      contrast-enhanced large tumor growing into right cavernous sinus and Meckel's
      cave located totally within intradural retroclival region. She underwent
      retromastoid suboccipital craniotomy to resect the tumor mass and adjuvant gamma
      knife radiosurgery for remnant tumor at 1 month after operation. Adjuvant
      radiosurgery after surgical excision seems to be effective for the treatment of
      intradural extraosseous chordomas.

PMID- 19763219
TI  - Endoscopic endonasal transsphenoidal resection of solitary extramedullary
      plasmacytoma in the sphenoid sinus with destruction of skull base.
AB  - Solitary extramedullary plasmacytomas are isolated plasma cell tumors of soft
      tissue that typically do not metastasize. They are rare and account for 4% of all
      plasma cell tumors. To our knowledge, only 14 cases of solitary extramedullary
      plasmacytomas in the sphenoid sinus have been reported. A 32-year-old man
      presented to our department with complaint of ocular pain in the right eyeball
      and diplopia. Physical and neurological examinations revealed intact and prompt
      direct and indirect light reflexes in both pupils and limitation of extraocular
      muscle movement seen with the lateral gaze of the right eyeball. Magnetic
      resonance imaging suggested the presence of mucocele or mycetoma, therefore
      surgical resection was performed with endoscopic endonasal transsphenoidal
      approach. Histopathology was consistent with plasmacytoma. Systemic work-up did
      not show any evidence of metastasis and the sphenoid sinus was the sole tumor
      site, and therefore the diagnosis of solitary extramedullary plasmacytoma was
      confirmed. We report a rare case of solitary extramedullary plasmacytoma in the
      sphenoid sinus with successful treatment using the endoscopic endonasal
      transsphenoidal resection and adjuvant radiotherapy.

PMID- 19763220
TI  - Intracranial plasma cell granuloma.
AB  - Plasma cell granuloma is a tumor-like disease characterized by non-neoplastic
      polyclonal proliferation of plasma cells and other mononuclear cells. This
      disease occurs most frequently in the lung and upper respiratory tract, while the
      involvement of the central nervous system is very rare. A 44-year-old female
      patient presented with nausea and progressive visual disturbance. Brain magnetic
      resonance imaging (MRI) revealed the mass along the right tentorium with low
      signal intensity in the T2 weighted image (T2WI) and fluid-attenuated inversion
      recovery (FLAIR) sequence, and an isosignal intensity in T1 weighted image
      (T1WI), the latter of which was enhanced after administration of gadolinium
      diethylenetriamine penta-acetic acid (Gd-DTPA). The thickest portion of the
      tentorium was partially excised via the combined suboccipital and infratentorial
      approach. The histopathological examination indicated a diagnosis of plasma cell
      granuloma. Postoperative steroid therapy was administered for remnant tumor
      control. Although a follow up MRI scan taken 20 months after the operation showed
      a slight decrease in tumor size, the lesion had extended to the falx and left
      frontal convexity along with parenchymal edema at 32 months after the operation
      and the clinical status was aggravated. The mass was removed from the left
      frontal convexity. Radiation therapy was given, together with steroid
      administration.

PMID- 19763221
TI  - Spinal Cord Stimulation for Intractable Visceral Pain due to Chronic
      Pancreatitis.
AB  - Pain caused by chronic pancreatitis is medically intractable and resistant to
      conventional interventional or surgical treatment. We report a case of spinal
      cord stimulation (SCS) for intractable pain due to chronic pancreatitis. The
      patient had a history of nonalcoholic chronic pancreatitis and multiple emergency
      room visits as well as repeated hospitalization including multiple nerve block
      and morphine injection for 3 years. We implanted surgical lead at T6-8 level on
      this patient after successful trial of percutaneous electrode. The patient
      experienced a decreased visual analog scale (VAS) scores for pain intensity and
      amount of opioid intake. The patient was followed for more than 14 months with
      good outcome and no further hospitalization. From our clinical case, spinal cord
      stimulation on intractable pain due to chronic pancreatitis revealed moderate
      pain control outcome. We suggest that SCS is an effective, noninvasive treatment
      option for abdominal visceral pain. Further studies and long term follow-up are
      needed to fully understand the effect of SCS on abdominal visceral pain.

PMID- 19763222
TI  - Intradural lumbar disc herniations associated with epidural adhesion : report of
      two cases.
AB  - Intradural lumbar disc herniation (ILDH) is rare. In this report, authors present
      2 cases of ILDHs associated with severe adhesion between the dural sac and
      posterior longitudinal ligament. In a 40-year-old man, ILDH occurred in
      association with epidural adhesion due to ossification of the posterior
      longitudinal ligament (OPLL). In other 31-year-old man, ILDH occurred in presence
      of epidural adhesion due to previous spine surgery.

PMID- 19763223
TI  - Spontaneous bilateral supratentorial subdural and retroclival extradural
      hematomas in association with cervical epidural venous engorgement.
AB  - We describe a case of 36-year-old man who presented with a subacute headache
      preceded by a 1-month history of posterior neck pain without trauma history. Head
      and neck magnetic resonance imaging (MRI) studies disclosed bilateral
      supratentorial subdural and retroclival extradural hematomas associated with
      marked cervical epidural venous engorgement. Cerebral and spinal angiography
      disclosed no abnormalities except dilated cervical epidural veins. We performed
      serial follow-up MRI studied to monitor his condition. Patient's symptoms
      improved gradually. Serial radiologic studies revealed gradual resolution of
      pathologic findings. A 3-month follow-up MRI study of the brain and cervical
      spine revealed complete resolution of the retroclival extradural hematoma,
      disappearance of the cervical epidural venous engorgement, and partial resolution
      of the bilateral supratentorial subdural hematoma. Complete resolution of the
      bilateral supratentorial subdural hematoma was confirmed on a 5-month follow-up
      brain MRI. The diagnosis and possible mechanisms of this rare association are
      discussed.

PMID- 19763224
TI  - The Impact of Neighborhood Context on Intragroup and Intergroup Robbery: The San
      Antonio Experience.
AB  - Guided by social disorganization theory, this article examines the influence of
      neighborhood characteristics on intragroup and intergroup robbery, net of spatial
      proximity in a predominantly native-born Latino/Mexican-origin city-San Antonio,
      Texas. From census tract and official police robbery data, the findings indicate
      that intragroup robbery is more common than intergroup robbery. Multivariate
      results show that variation in black intra-group robbery lies primarily in highly
      disadvantaged neighborhoods; whereas variation in Latino intergroup robbery is
      found in neighborhoods with more disadvantage, racial/ethnic heterogeneity,
      recent immigrants, and blacks. Residential instability persistently influences
      all robbery types. Disaggregating robberies by race and ethnicity reveals the
      importance of examining Latinos as offenders and victims. The case of San Antonio
      serves as a harbinger of conditions that may exist in the growing number of
      majority-Latino cities-and suggests the need to investigate crime experiences
      that move beyond studying racial dichotomies of violence.

PMID- 19763225
TI  - Eye Movement Patterns for Novice Teen Drivers Does 6 Months of Driving Experience
      Make a Difference?
AB  - Attention to the road is essential to safe driving, but the development of
      appropriate eye glance scanning behaviors may require substantial driving
      experience. Novice teen drivers may focus almost exclusively on the road ahead
      rather than scanning the mirrors, and when performing secondary tasks, they may
      spend more time with eyes on the task than on the road. This paper examines the
      extent to which the scanning of novice teens improves with experience. For this
      study, 18 novice teen (younger than 17.5 years old) and 18 experienced adult
      drivers performed a set of in-vehicle tasks and a baseline driving segment on a
      test track, the teens within 4 weeks of licensure and then again 6 months later.
      This paper addresses the following questions: Did teen eye glance performance
      improve from initial assessment? Did teens and adults still differ after 6
      months? Results for some tasks showed that rearview and left mirror-window (LM-W)
      glances improved for teens from initial testing to the 6-month follow-up and that
      some differences between teens and adults at initial testing were no longer
      significant at the 6-month follow-up, suggesting significant learning effects.
      The frequency of rearview and LM-W glances during secondary tasks improved among
      teens at the 6-month follow-up, but teens still had significantly fewer glances
      to mirrors than did adults when engaged in a secondary task.

PMID- 19763226
TI  - Learning to talk in a gesture-rich world: Early communication in Italian vs.
      American children.
AB  - Italian children are immersed in a gesture-rich culture. Given the large gesture
      repertoire of Italian adults, young Italian children might be expected to develop
      a larger inventory of gestures than American children. If so, do these gestures
      impact the course of language learning? We examined gesture and speech production
      in Italian and US children between the onset of first words and the onset of two
      word combinations. We found differences in the size of the gesture repertoires
      produced by the Italian vs. the American children, differences that were
      inversely related to the size of the children's spoken vocabularies. Despite
      these differences in gesture vocabulary, in both cultures we found that gesture +
      speech combinations reliably predicted the onset of two-word combinations,
      underscoring the robustness of gesture as a harbinger of linguistic development.

PMID- 19763227
TI  - Effect of Verb Network Strengthening Treatment (VNeST) on Lexical Retrieval of
      Content Words in Sentences in Persons with Aphasia.
AB  - BACKGROUND: Verb Network Strengthening Treatment (VNeST) is a semantic treatment
      that aims to improve lexical retrieval of content words in sentence context by
      promoting systematic retrieval of verbs (e.g., measure) and their thematic roles
      (i.e., agent (doer of the action, e.g., carpenter, chef)) and patient (receiver
      of the action, e.g., lumber, sugar)). VNeST is influenced by Loverso and
      colleagues (e.g., Loverso, Selinger, and Prescott, 1979), who used "verb as core"
      treatment to improve sentence production with encouraging results, and McRae and
      colleagues, who showed that verbs prime typical agents (e.g., pray-nun) and
      patients (arrest-criminal) (Ferretti, McRae, & Hatherell, 2001) and vice-versa
      (McRae, Hare, Elman, & Ferretti, 2005). AIMS: There are four specific questions
      in this study. Does training a set of verbs using VNeST generalize to the ability
      to produce 1) an agent (carpenter), trained verb (measure), and patient (stairs)
      in response to novel picture stimuli and 2) an agent (nurse), untrained
      semantically related verb (weigh), and patient (baby) in response to novel
      picture stimuli? 3) Are generalization effects maintained?, and 4) Does VNeST
      generalize to the ability to retrieve nouns and verbs not directly related to
      treatment items in single word naming, picture description and connected speech
      tasks? METHODS #ENTITYSTARTX00026; PROCEDURES: Four participants with aphasia
      participated. Participants received VNeST, which involves retrieval of agent
      patient pairs (e.g., chef/sugar, surveyor/land) related to trained verbs (e.g.,
      measure), two times per week. A single subject, repeated probe, multiple baseline
      experimental design was used. Generalization to sentence production for sentences
      containing trained verbs and untrained semantically related verbs was tested
      weekly. OUTCOMES #ENTITYSTARTX00026; RESULTS: Results demonstrated generalization
      to lexical retrieval of content words in sentences with trained and untrained
      verbs across participants. Additionally, pre- to post-treatment generalization
      was observed on single verb and noun naming and lexical retrieval in sentences
      across a variety of tasks across participants. Generalization to connected speech
      was observed for 3 of 4 participants. CONCLUSIONS: Though preliminary, these
      results indicate that VNeST may be effective in promoting generalization from
      single word naming to connected speech in persons with moderate aphasia. A number
      of clinical implications related to treatment efficiency are discussed.

PMID- 19763228
TI  - Ultrastructural analyses of nanoscale apatite biomimetically grown on organic
      template.
AB  - The ultrastructure of nanoscale apatite biomimetically formed on an organic
      template from a supersaturated mineralizing solution was studied to examine the
      morphological and crystalline arrangement of mineral apatites. Needle-shaped
      apatite crystal plates with a size distribution of ~100 to ~1000 nm and the long
      axis parallel to the c axis ([002]) were randomly distributed in the mineral
      films. Between these randomly distributed needle-shaped apatite crystals,
      amorphous phases and apatite crystals (~20-40 nm) with the normal of the grains
      quasi-perpendicular to the c axis were observed. These observations suggest that
      the apatite film is an interwoven structure of amorphous phases and apatite
      crystals with various orientations. The mechanisms underlying the shape of the
      crystalline apatite plate and aggregated apatite nodules are discussed from an
      energy-barrier point of view. The plate or needle-shaped apatite is favored in
      single-crystalline form, whereas the granular nodules are favored in the
      polycrystalline apatite aggregate. The similarity in shape in both single
      crystalline needle-shaped apatite and polycrystalline granular apatite over a
      wide range of sizes is explained by the principle of similitude, in which the
      growth and shape are determined by the forces acting upon the surface area and
      the volume.

PMID- 19763229
TI  - Counseling Psychology and Chronic Health Conditions: A Call for Action.
AB  - The authors support the assertion that counseling psychology expertise should be
      present at all levels of therapeutic activity that may benefit persons who live
      with chronic health conditions. They consider the impact of the increasing rates
      of chronic health conditions on health care systems, society, and health service
      professions. In order for the field to have an influential role in service
      delivery and policy formation that benefit individuals with chronic health
      conditions, the authors offer four recommendations: (a) Participate in, promote,
      and reward interdisciplinary research and service; (b) conduct, promote, and
      reward policy-relevant research programs; (c) promote and utilize participatory
      research methods; and (d) consider the implications of these activities for our
      training programs.

PMID- 19763231
TI  - A Bayesian analysis for longitudinal semicontinuous data with an application to
      an acupuncture clinical trial.
AB  - In many biomedical applications, researchers encounter semicontinuous data where
      data are either continuous or zero. When the data are collected over time the
      observations may be correlated. Analysis of this kind of longitudinal
      semicontinuous data is challenging due to the presence of strong skewness in the
      data. A flexible class of zero-inflated models in a longitudinal setting is
      developed. A Bayesian approach is used to analyze longitudinal data from an
      acupuncture clinical trial, in which the effects of active acupuncture, sham
      acupuncture and standard medical care is compared on chemotherapy-induced nausea
      in patients who were treated for advanced breast cancer. A spline model is
      introduced into the linear predictor of the model to explore the possibility of a
      nonlinear treatment effect. Possible serial correlation between successive
      observations is also accounted using the Brownian motion. Thus, the approach
      taken in this paper provides for a more flexible modeling framework and, with the
      use of WinBUGS, provides for a computationally simpler approach than direct
      maximum-likelihood. The Bayesian methodology is illustrated with the acupuncture
      clinical trial data.

PMID- 19763230
TI  - Promyelocytic leukemia-nuclear body proteins: herpesvirus enemies, accomplices,
      or both?
AB  - The promyelocytic leukemia (PML) protein gathers other cellular proteins, such as
      Daxx and Sp100, to form subnuclear structures termed PML-nuclear bodies (PML-NBs)
      or ND10 domains. Many infecting viral genomes localize to PML-NBs, leading to
      speculation that these structures may represent the most efficient subnuclear
      location for viral replication. Conversely, many viral proteins modify or disrupt
      PML-NBs, suggesting that viral replication may be more efficient in the absence
      of these structures. Thus, a debate remains as to whether PML-NBs inhibit or
      enhance viral replication. Here we review and discuss recent data indicating that
      for herpesviruses, PML-NB proteins inhibit viral replication in cell types where
      productive, lytic replication occurs, while at the same time may enhance the
      establishment of lifelong latent infections in other cell types.

PMID- 19763232
TI  - First observation of surface plasmon-coupled electrochemiluminescence.
AB  - Electrochemiluminescence (ECL) is often used for high sensitivity detection. We
      describe a new approach to collecting the ECL signal, by coupling of the excited
      state of [Ru(bpy)(3)](2+) with the surface plasmons in a thin gold film. The
      energy then radiates into the substrate at a defined angle. Surface plasmon
      coupled ECL promises to be useful in chemical and biological assays.

PMID- 19763233
TI  - AUTOMATIC GENERATION OF FFT FOR TRANSLATIONS OF MULTIPOLE EXPANSIONS IN SPHERICAL
      HARMONICS.
AB  - The fast multipole method (FMM) is an efficient algorithm for calculating
      electrostatic interactions in molecular simulations and a promising alternative
      to Ewald summation methods. Translation of multipole expansion in spherical
      harmonics is the most important operation of the fast multipole method and the
      fast Fourier transform (FFT) acceleration of this operation is among the fastest
      methods of improving its performance. The technique relies on highly optimized
      implementation of fast Fourier transform routines for the desired expansion
      sizes, which need to incorporate the knowledge of symmetries and zero elements in
      the input arrays. Here a method is presented for automatic generation of such,
      highly optimized, routines.

PMID- 19763234
TI  - Single-Molecule Studies of Enhanced Fluorescence on Silver Island Films.

PMID- 19763235
TI  - Metal-enhanced fluorescent biomarkers for cardiac risk assessment.
AB  - In this presentation we describe a novel methodology for ultra-sensitive
      fluorescence immunoassays based on a new class of fluorescent biomarkers, which
      are strongly enhanced by nano-size metallic particles. Specifically, we discuss
      development of the immunoassay on the surfaces coated with metallic particles for
      high sensitivity detection of cardiac markers. This technology will allow
      detection of the biomarkers in serum and blood without separation and
      amplification steps. We present an experimental platform that uses front-face
      excitation in total internal reflection mode for efficient rejection of
      background fluorescence.

PMID- 19763236
TI  - Radiative decay engineering: the role of photonic mode density in biotechnology.
AB  - Fluorescence detection is a central technology in biological research and
      biotechnology. A vast array of fluorescent probes are available with diverse
      spectral properties. These properties were 'engineered' into fluorophores by
      modification of the chemical structures. Essentially, all present uses of
      fluorescence rely on the radiation of energy into optically transparent media,
      the free space which surrounds the fluorophores. In this paper, we summarize an
      opportunity for novel fluorescence technology based on modification of the
      photonic mode density around the fluorophore and thus control of its spectral
      properties. This modification can be accomplished by proximity of fluorophores to
      metallic particles of gold, silver and possibly others. By engineering the size
      and shape of the metal particles, and the location of the fluorophores relative
      to the surfaces, fluorophores can be quenched, display increases in quantum
      yield, and changes in lifetime. Fluorophore-metal surface combinations can even
      display directional rather than isotropic emission. We describe recent
      experimental results and suggest potential biomedical applications of fluorophore
      metal particle interactions.

PMID- 19763237
TI  - Effect of poly (sodium 4-styrene sulfonate) on the morphology of hydroxyapatite
      particles.
AB  - Nanorods hydroxyapatite, (HAP) Ca(10)(PO(4))(6)(OH)(2) is successfully prepared
      by water in oil microemulsion using, CaCL(2) and H(3)PO(4) (water phase),
      poly(sodium 4-styrene sulfonate) (PSSS) as template and cyclohexane as oil phase.
      The nano-structure of the product was studied by means of X-ray diffraction
      (XRD), Fourier transmission infrared spectrometer (FT-IR), scanning electron
      microscopy (SEM), and atomic force microscope (AFM). With this system, we could
      synthesize nano-particles of hydroxyapatite with high crystallinity and least
      agglomeration.

PMID- 19763238
TI  - Gastrointestinal stromal tumor in pregnancy: a case report.
AB  - Background. Gastrointestinal stromal tumors (GISTs) are the most common
      mesenchymal tumors of the digestive tract and are diagnosed relatively seldom in
      pregnancy. Case. We describe a remarkable clinical course and long-term outcome,
      now nine years after first diagnosis, of a massive and metastatic, with a high
      malignancy grade GIST case, found in and treated from the first trimester of
      pregnancy onwards. Conclusion. GIST occurring during pregnancy is extremely rare.
      However, early diagnosis is important for optimal management. The recent better
      understanding of oncogenesis, the use of immunohistochemistry for differential
      diagnosis of GISTs, and the use of imatinib mesylate as the treatment of first
      choice are-as shown in this case-important for care of pregnant women with this
      type of malignancy.

PMID- 19763239
TI  - Ricco's Areas for S- and L-Cone Mechanisms Across the Retina.
AB  - The purposes of this study were to measure areas of complete spatial summation
      (i.e., Ricco's area) for S- and L-cone mechanisms and to evaluate whether the
      sizes of Ricco's area could be explained in terms of either the densities of
      photoreceptors or ganglion cells. Increment thresholds were measured at the fovea
      and at 1.5 degrees , 4 degrees , 8 degrees , and 20 degrees  in the superior
      retina using a temporal two-alternative forced-choice procedure. Test stimuli
      ranging from -0.36 to 4.61 log area (min(2)) were presented on concentric 12.3
      degrees  adapting and auxiliary fields, which isolated either an S- or L-cone
      mechanism on the plateau of the respective threshold vs. intensity function. The
      data indicate that from 0-20 degrees  retinal eccentricity, the size of Ricco's
      area is larger for the S-cone mechanism than the L-cone mechanism, increases
      monotonically for the L-cone mechanism, and, for both cone mechanisms, increases
      between 8-20 degrees  retinal eccentricity. This latter finding suggests that
      ganglion cell density rather than cone density defines the size of Ricco's area
      in the parafoveal and peripheral retina.

PMID- 19763240
TI  - Magnetic nanoparticles with functional silanes: evolution of well-defined shells
      from anhydride containing silane.
AB  - Modification of iron oxide nanoparticles (NPs) synthesized by high temperature
      solvothermal routes is carried out using two silanes: (i) N-(6-aminohexyl)
      aminopropyltrimethoxysilane (AHAPS) where only one end of the molecule reacts
      with the surface Fe-OH groups and (ii) 3-(triethoxysilyl)propylsuccinic anhydride
      (SSA) where both ends are reactive with Fe-OH. Depending on the NP synthesis
      protocol, the amount of surface OH groups on the NPs may differ, however, for all
      the cases presented here, the comparatively low OH group density prevents a high
      density of AHAPS coverage, yielding NP aggregates instead of single particles in
      aqueous solutions. Alternatively, use of SSA containing two terminal
      functionalities, anhydride and siloxy, which are both reactive towards the NP
      surface, results in the formation of discrete dense polymeric shells, providing
      stability of individual NPs in water. The mechanism of the SSA shell formation is
      discussed. The evolution of the chemical transformations leads to shells of
      different thickness and density, yet this evolution can be halted by hydrolysis,
      after which the NPs are water soluble, negatively charged and exhibit excellent
      stability in aqueous media.

PMID- 19763241
TI  - Social Network Centrality and Leadership Status: Links with Problem Behaviors and
      Tests of Gender Differences.
AB  - Seventh-grade students (N = 324) completed social cognitive maps to identify peer
      groups and peer group leaders, sociometric nominations to describe their peers'
      behaviors, and questionnaires to assess their own behaviors. Peer group members
      resembled one another in levels of direct and indirect aggression and substance
      use; girls' cliques were more behaviorally homogenous than were boys' cliques. On
      average, leaders (especially if they were boys) were perceived as engaging in
      more problem behaviors than were nonleaders. In girls' cliques, peripheral group
      members were more similar to their group leader on indirect aggression than were
      girls who were more central to the clique. Peer leaders perceived themselves as
      being more able to influence peers but did not differ from nonleaders in their
      perceived susceptibility to peer influence. The findings contribute to our
      understanding of processes through which influence may occur in adolescent peer
      groups.

PMID- 19763242
TI  - Applications of Carbon Nanotubes in Biotechnology and Biomedicine.
AB  - Due to their electrical, chemical, mechanical and thermal properties, carbon
      nanotubes are one of the most promising materials for the electronics, computer
      and aerospace industries. Here, we discuss their properties in the context of
      future applications in biotechnology and biomedicine. The purification and
      chemical modification of carbon nanotubes with organic, polymeric and biological
      molecules are discussed. Additionally we review their uses in biosensors,
      assembly of structures and devices, scanning probe microscopy and as substrates
      for neuronal growth. We note that additional toxicity studies of carbon nanotubes
      are necessary so that exposure guidelines and safety regulations can be
      established in a timely manner.

PMID- 19763243
TI  - Design of Metalloporphyrin-Based Dendritic Nanoprobes for Two-Photon Microscopy
      of Oxygen.
AB  - Metalloporphyrin-based phosphorescent nanoprobes are being developed for two
      photon microscopy of oxygen. In these molecular constructs generation of
      porphyrin triplet states upon two-photon excitation is induced upon the
      intramolecular Forster-type resonance energy transfer from a covalently attached
      2P antenna. In the earlier developed prototypes, electron transfer between the
      antenna and the metalloporphyrin strongly interfered with the phosphorescence,
      reducing the sensitivity and the dynamic range of the sensors. By tuning the
      distances between the antenna and the core and adjusting their redox potentials
      the unwanted electron transfer could be prevented. An array of phosphorescent Pt
      porphyrins (energy transfer acceptors) and 2P dyes (energy transfer donors) was
      screened using dynamic quenching of phosphorescence, and the FRET-pair with the
      minimal ET rate was identified. This pair, consisting of Coumarin-343 and Pt meso
      tetra-(4-alkoxyphenyl)porphyrin, was used to construct a probe in which the
      antenna fragments were linked to the termini of G3 poly(arylglycine) (AG)
      dendrimer with PtP core. The folded dendrimer formed an insulating layer between
      the porphyrin and the antenna, simultaneously controlling the rate of oxygen
      quenching (Stern-Volmer oxygen quenching constant). Modification of the dendrimer
      periphery with oligoethyleneglycol residues made the probe's signal insensitive
      to the presence of proteins and other macromolecular solutes.

PMID- 19763244
TI  - Tunable Phosphoramidite Ligands for Asymmetric Hydrovinylation: Ligands par
      excellence for Generation of All-Carbon Quaternary Centers.
AB  - 1-Alkylstyrenes undergo efficient hydrovinylation (addition of ethylene) in the
      presence of a Ni-catalyst prepared from [(allyl)NiBr](2), Na(+) [BAr(4)](-) (Ar =
      3,5-bis-trifluromethylphenyl), and a phosphoramidite ligand giving products in
      excellent yields and enantioselectivities. In many cases phosphoramidites derived
      from achiral 2,2'-biphenol are almost as good as ligands derived from the more
      expensive enantiopure 2,2'-binaphthols. The hydrovinylation products, which carry
      two versatile latent functionalities, an aryl and a vinyl group, are potentially
      useful for the synthesis of several important natural products containing
      benzylic all-carbon quaternary centers.

PMID- 19763245
TI  - Multi-Target Approaches in Colon Cancer Chemoprevention Based on Systems Biology
      of Tumor Cell-Signaling.
AB  - Colorectal cancer is the leading cause of cancer related deaths in the United
      States. Although it is preventable, thousands of lives are lost each year in the
      U.S. to colorectal cancer than to breast cancer and AIDS combined. In colon
      cancer, the formation and progression of precancerous lesions like aberrant crypt
      foci and polyps is associated with the up-regulation of cycloxygenase-2 (COX-2),
      inducible nitric oxide synthase (iNOS) and hydroxy methyl glutaryl CoA reductase
      (HMG-CoA reductase). The current review will focus on the signaling pathway
      involving COX-2 and HMG-CoA reductase enzymes and their downstream effectors in
      signaling mechanism. Cancer cells need huge pools of both cholesterol and
      isoprenoids to sustain their unlimited growth potential. Cholesterol by
      modulating caveolae formation regulates several signaling molecules like AKT,
      IGFR, EGFR and Rho which are involved in cell growth and survival. Cholesterol is
      also essential for lipid body formation which serves as storage sites for COX-2,
      eicosanoids and caveolin-1. Experimental studies have identified important
      mechanisms showing that COX-2, caveolin-1, lipid bodies and prenylated proteins
      is involved in carcinogenesis. Therefore multi-target, multi-drug approach is the
      ideal choice for effective colon cancer chemoprevention. This review will give an
      overview of the two pathways, their signaling networks, and the interactions
      between the components of the two networks in the activation and regulation of
      cell signaling involving growth/survival and explain the rationale for colon
      cancer chemoprevention using COX-2 inhibitors and statins.

PMID- 19763246
TI  - Measuring Children's Media Use in the Digital Age: Issues and Challenges.
AB  - In this new and rapidly changing era of digital technology, there is increasing
      consensus among media scholars that there is an urgent need to develop
      measurement approaches which more adequately capture media use The overarching
      goal of this paper is facilitate the development of measurement approaches
      appropriate for capturing children's media use in the digital age. The paper
      outlines various approaches to measurement, focusing mainly on those which have
      figured prominently in major existing studies of children's media use. We
      identify issues related to each technique, including advantages and
      disadvantages. We also include a review of existing empirical comparisons of
      various methodologies. The paper is intended to foster discussion of the best
      ways to further research and knowledge regarding the impact of media on children.

PMID- 19763247
TI  - Age-Related Increases in Photopic Increment Thresholds Are Not Due to an
      Elevation in Intrinsic Noise.
AB  - Threshold vs. intensity (tvi) functions were measured under conditions in which
      the slope of the rising branch approximated the deVries-Rose law in order to
      evaluate the contribution of intrinsic visual noise (dark light, Eigengrau) to
      age-related elevations in threshold under photopic conditions. Data were obtained
      from 48 observers (20-88 years) using a temporal 2AFC procedure. The stimulus was
      centered at 8 degrees  nasal retinal eccentricity and consisted of a 560 nm,
      14.4' test flash (10 ms) concentric with a steady 500 nm (12.9 degrees ) adapting
      field (13 intensity levels ranging from 0-9 log quanta . sec(-1) . deg(-2)),
      which resulted in clear scotopic and photopic branches. Photopic thresholds
      increased linearly with age at a rate of 0.08 log unit per decade at the cornea.
      The mean slope of the rising portion of the tvi functions (in log-log
      coordinates) was 0.62, and not correlated with age. Dark light values increased
      with age, but not significantly. Dark light was a statistically significant
      predictor of individual differences in absolute photopic threshold, but it is not
      responsible for age-related increases in threshold under photopic conditions.

PMID- 19763248
TI  - ABSENCE SEIZURES AS RESETTING MECHANISMS OF BRAIN DYNAMICS.
AB  - To understand the increase in age-related incidence and frequency of absence
      seizures in the rat brain, we investigated the effect of these seizures on brain
      dynamics. This paper puts forward the hypothesis that age-related differences in
      the expression of absence seizures are associated with the ability of the
      seizures to reset brain dynamics.

PMID- 19763249
TI  - Learning words by hand: Gesture's role in predicting vocabulary development.
AB  - Children vary widely in how quickly their vocabularies grow. Can looking at early
      gesture use in children and parents help us predict this variability? We
      videotaped 53 English-speaking parent-child dyads in their homes during their
      daily activities for 90-minutes every four months between child age 14 and 34
      months. At 42 months, children were given the Peabody Picture Vocabulary Test
      (PPVT). We found that child gesture use at 14 months was a significant predictor
      of vocabulary size at 42 months, above and beyond the effects of parent and child
      word use at 14 months. Parent gesture use at 14 months was not directly related
      to vocabulary development, but did relate to child gesture use at 14 months
      which, in turn, predicted child vocabulary. These relations hold even when
      background factors such as socio-economic status are controlled. The findings
      underscore the importance of examining early gesture when predicting child
      vocabulary development.

PMID- 19763251
TI  - Component analysis of a new Solid State X-ray Image Intensifier (SSXII) using
      photon transfer and Instrumentation Noise Equivalent Exposure (INEE)
      measurements.
AB  - The SSXII is a novel x-ray imager designed to improve upon the performance
      limitations of conventional dynamic radiographic/fluoroscopic imagers related to
      resolution, charge-trapping, frame-rate, and instrumentation-noise. The SSXII
      consists of a CsI:Tl phosphor coupled via a fiber-optic taper (FOT) to an
      electron-multiplying CCD (EMCCD). To facilitate investigational studies, initial
      designs enable interchangeability of such imaging components. Measurements of
      various component and configuration characteristics enable an optimization
      analysis with respect to overall detector performance. Photon transfer was used
      to characterize the EMCCD performance including ADC sensitivity, read-noise, full
      well capacity and quantum efficiency. X-ray sensitivity was measured using RQA x
      ray spectra. Imaging components were analyzed in terms of their MTF and
      transmission efficiency. The EMCCD was measured to have a very low effective read
      noise of less than 1 electron rms at modest EMCCD gains, which is more than two
      orders-of-magnitude less than flat panel (FPD) and CMOS-based detectors. The
      variable signal amplification from 1 to 2000 times enables selectable
      sensitivities ranging from 8.5 (168) to over 15k (300k) electrons per incident x
      ray photon with (without) a 4:1 FOT; these sensitivities could be readily
      increased with further component optimization. MTF and DQE measurements indicate
      the SSXII performance is comparable to current state-of-the-art detectors at low
      spatial frequencies and far exceeds them at higher spatial frequencies. The
      instrumentation noise equivalent exposure (INEE) was measured to be less than 0.3
      MUR out to 10 cycles/mm, which is substantially better than FPDs. Component
      analysis suggests that these improvements can be substantially increased with
      further detector optimization.

PMID- 19763252
TI  - Angiographic analysis of animal model aneurysms treated with novel polyurethane
      asymmetric vascular stent (P-AVS): feasibility study.
AB  - Image-guided endovascular intervention (EIGI), using new flow modifying
      endovascular devices for intracranial aneurysm treatment is an active area of
      stroke research. The new polyurethane-asymmetric vascular stent (P-AVS), a
      vascular stent partially covered with a polyurethane-based patch, is used to
      cover the aneurysm neck, thus occluding flow into the aneurysm. This study
      involves angiographic imaging of partially covered aneurysm orifices. This
      particular situation could occur when the vascular geometry does not allow full
      aneurysm coverage. Four standard in-vivo rabbit-model aneurysms were
      investigated; two had stent patches placed over the distal region of the aneurysm
      orifice while the other two had stent patches placed over the proximal region of
      the aneurysm orifice. Angiographic analysis was used to evaluate aneurysm blood
      flow before and immediately after stenting and at four-week follow-up. The
      treatment results were also evaluated using histology on the aneurysm dome and
      electron microscopy on the aneurysm neck. Post-stenting angiographic flow
      analysis revealed aneurysmal flow reduction in all cases with faster flow in the
      distally-covered case and very slow flow and prolonged pooling for proximal
      coverage. At follow-up, proximally-covered aneurysms showed full dome occlusion.
      The electron microscopy showed a remnant neck in both distally-placed stent cases
      but complete coverage in the proximally-placed stent cases. Thus, direct flow
      (impingement jet) removal from the aneurysm dome, as indicated by angiograms in
      the proximally-covered case, was sufficient to cause full aneurysm healing in
      four weeks; however, aneurysm healing was not complete for the distally-covered
      case. These results support further investigations into the treatment of
      aneurysms by flow-modification using partial aneurysm-orifice coverage.

PMID- 19763253
TI  - Unsupervised Adaptation of Categorical Prosody Models for Prosody Labeling and
      Speech Recognition.
AB  - Automatic speech recognition (ASR) systems rely almost exclusively on short-term
      segment-level features (MFCCs), while ignoring higher level suprasegmental cues
      that are characteristic of human speech. However, recent experiments have shown
      that categorical representations of prosody, such as those based on the Tones and
      Break Indices (ToBI) annotation standard, can be used to enhance speech
      recognizers. However, categorical prosody models are severely limited in scope
      and coverage due to the lack of large corpora annotated with the relevant
      prosodic symbols (such as pitch accent, word prominence, and boundary tone
      labels). In this paper, we first present an architecture for augmenting a
      standard ASR with symbolic prosody. We then discuss two novel, un-supervised
      adaptation techniques for improving, respectively, the quality of the linguistic
      and acoustic components of our categorical prosody models. Finally, we implement
      the augmented ASR by enriching ASR lattices with the adapted categorical prosody
      models. Our experiments show that the proposed unsupervised adaptation techniques
      significantly improve the quality of the prosody models; the adapted prosodic
      language and acoustic models reduce binary pitch accent (presence versus absence)
      classification error rate by 13.8% and 4.3%, respectively (relative to the seed
      models) on the Boston University Radio News Corpus, while the prosody-enriched
      ASR exhibits a 3.1% relative reduction in word error rate (WER) over the baseline
      system.

PMID- 19763254
TI  - An introspective comparison of random forest-based classifiers for the analysis
      of cluster-correlated data by way of RF++.
AB  - Many mass spectrometry-based studies, as well as other biological experiments
      produce cluster-correlated data. Failure to account for correlation among
      observations may result in a classification algorithm overfitting the training
      data and producing overoptimistic estimated error rates and may make subsequent
      classifications unreliable. Current common practice for dealing with replicated
      data is to average each subject replicate sample set, reducing the dataset size
      and incurring loss of information. In this manuscript we compare three approaches
      to dealing with cluster-correlated data: unmodified Breiman's Random Forest
      (URF), forest grown using subject-level averages (SLA), and RF++ with subject
      level bootstrapping (SLB). RF++, a novel Random Forest-based algorithm
      implemented in C++, handles cluster-correlated data through a modification of the
      original resampling algorithm and accommodates subject-level classification.
      Subject-level bootstrapping is an alternative sampling method that obviates the
      need to average or otherwise reduce each set of replicates to a single
      independent sample. Our experiments show nearly identical median classification
      and variable selection accuracy for SLB forests and URF forests when applied to
      both simulated and real datasets. However, the run-time estimated error rate was
      severely underestimated for URF forests. Predictably, SLA forests were found to
      be more severely affected by the reduction in sample size which led to poorer
      classification and variable selection accuracy. Perhaps most importantly our
      results suggest that it is reasonable to utilize URF for the analysis of cluster
      correlated data. Two caveats should be noted: first, correct classification error
      rates must be obtained using a separate test dataset, and second, an additional
      post-processing step is required to obtain subject-level classifications. RF++ is
      shown to be an effective alternative for classifying both clustered and non
      clustered data. Source code and stand-alone compiled versions of command-line and
      easy-to-use graphical user interface (GUI) versions of RF++ for Windows and Linux
      as well as a user manual (Supplementary File S2) are available for download at:
      http://sourceforge.org/projects/rfpp/ under the GNU public license.

PMID- 19763255
TI  - Determination of EGFR endocytosis kinetic by auto-regulatory association of PLD1
      with mu2.
AB  - BACKGROUND: Upon ligand binding, cell surface signaling receptors are
      internalized through a process tightly regulated by endocytic proteins and
      adaptor protein 2 (AP2) to orchestrate them. Although the molecular identities
      and roles of endocytic proteins are becoming clearer, it is still unclear what
      determines the receptor endocytosis kinetics which is mainly regulated by the
      accumulation of endocytic apparatus to the activated receptors.
      METHODOLOGY/PRINCIPAL FINDINGS: Here we employed the kinetic analysis of
      endocytosis and adaptor recruitment to show that mu2, a subunit of AP2 interacts
      directly with phospholipase D (PLD)1, a receptor-associated signaling protein and
      this facilitates the membrane recruitment of AP2 and the endocytosis of epidermal
      growth factor receptor (EGFR). We also demonstrate that the PLD1-mu2 interaction
      requires the binding of PLD1 with phosphatidic acid, its own product.
      CONCLUSIONS/SIGNIFICANCE: These results suggest that the temporal regulation of
      EGFR endocytosis is achieved by auto-regulatory PLD1 which senses the receptor
      activation and triggers the translocation of AP2 near to the activated receptor.

PMID- 19763256
TI  - A modified consumer inkjet for spatiotemporal control of gene expression.
AB  - This paper presents a low-cost inkjet dosing system capable of continuous, two
      dimensional spatiotemporal regulation of gene expression via delivery of
      diffusible regulators to a custom-mounted gel culture of E. coli. A consumer
      grade, inkjet printer was adapted for chemical printing; E. coli cultures were
      grown on 750 microm thick agar embedded in micro-wells machined into commercial
      compact discs. Spatio-temporal regulation of the lac operon was demonstrated via
      the printing of patterns of lactose and glucose directly into the cultures; X-Gal
      blue patterns were used for visual feedback. We demonstrate how the bistable
      nature of the lac operon's feedback, when perturbed by patterning lactose
      (inducer) and glucose (inhibitor), can lead to coordination of cell expression
      patterns across a field in ways that mimic motifs seen in developmental biology.
      Examples of this include sharp boundaries and the generation of traveling waves
      of mRNA expression. To our knowledge, this is the first demonstration of reaction
      diffusion effects in the well-studied lac operon. A finite element reaction
      diffusion model of the lac operon is also presented which predicts pattern
      formation with good fidelity.

PMID- 19763257
TI  - Clostridium perfringens epsilon toxin increases the small intestinal permeability
      in mice and rats.
AB  - Epsilon toxin is a potent neurotoxin produced by Clostridium perfringens types B
      and D, an anaerobic bacterium that causes enterotoxaemia in ruminants. In the
      affected animal, it causes oedema of the lungs and brain by damaging the
      endothelial cells, inducing physiological and morphological changes. Although it
      is believed to compromise the intestinal barrier, thus entering the gut
      vasculature, little is known about the mechanism underlying this process. This
      study characterizes the effects of epsilon toxin on fluid transport and
      bioelectrical parameters in the small intestine of mice and rats. The
      enteropooling and the intestinal loop tests, together with the single-pass
      perfusion assay and in vitro and ex vivo analysis in Ussing's chamber, were all
      used in combination with histological and ultrastructural analysis of mice and
      rat small intestine, challenged with or without C. perfringens epsilon toxin.
      Luminal epsilon toxin induced a time and concentration dependent intestinal fluid
      accumulation and fall of the transepithelial resistance. Although no evident
      histological changes were observed, opening of the mucosa tight junction in
      combination with apoptotic changes in the lamina propria were seen with
      transmission electron microscopy. These results indicate that C. perfringens
      epsilon toxin alters the intestinal permeability, predominantly by opening the
      mucosa tight junction, increasing its permeability to macromolecules, and
      inducing further degenerative changes in the lamina propria of the bowel.

PMID- 19763258
TI  - Association and interaction analyses of GABBR1 and GABBR2 with nicotine
      dependence in European- and African-American populations.
AB  - Previous studies have demonstrated that the gamma-aminobutyric acid type B
      (GABA(B)) receptor plays an essential role in modulating neurotransmitter release
      and regulating the activity of ion channels and adenyl cyclase. However, whether
      the naturally occurring polymorphisms in the two GABA(B) receptor subunit genes
      interact with each other to alter susceptibility to nicotine dependence (ND)
      remains largely unknown. In this study, we genotyped 5 and 33 single nucleotide
      polymorphisms (SNPs) for GABA(B) receptor subunit 1 and 2 genes (GABBR1, GABBR2),
      respectively, in a sample of 2037 individuals from 602 nuclear families of
      African- American (AA) or European-American (EA) origin. We conducted association
      analyses to determine (1) the association of each subunit gene with ND at both
      the individual SNP and haplotype levels and (2) the collective effect(s) of SNPs
      in both GABA(B) subunits on the development of ND. Several individual SNPs and
      haplotypes in GABBR2 were significantly associated with ND in both ethnic
      samples. Two haplotypes in AAs and one haplotype in EAs showed a protective
      effect against ND, whilst two other haplotypes in AAs and three haplotypes in EAs
      showed a risk effect for developing ND. Interestingly, these significant
      haplotypes were confined to two regions of GABBR2 in the AA and EA samples.
      Additionally, we found two minor haplotypes in GABBR1 to be positively associated
      with Heaviness of Smoking Index (HSI) in the EA sample. Finally, we demonstrated
      the presence of epistasis between GABBR1 and GABBR2 for developing ND. The
      variants of GABBR1 and GABBR2 are significantly associated with ND, and the
      involvement of GABBR1 is most likely through its interaction with GABBR2, whereas
      GABBR2 polymorphisms directly alter susceptibility to ND. Future studies are
      needed with more dense SNP coverage of GABBR1 and GABBR2 to verify the epistatic
      effects of the two subunit genes.

PMID- 19763259
TI  - Gene expression profiling in cells with enhanced gamma-secretase activity.
AB  - BACKGROUND: Processing by gamma-secretase of many type-I membrane protein
      substrates triggers signaling cascades by releasing intracellular domains (ICDs)
      that, following nuclear translocation, modulate the transcription of different
      genes regulating a diverse array of cellular and biological processes. Because
      the list of gamma-secretase substrates is growing quickly and this enzyme is a
      cancer and Alzheimer's disease therapeutic target, the mapping of gamma-secretase
      activity susceptible gene transcription is important for sharpening our view of
      specific affected genes, molecular functions and biological pathways.
      METHODOLOGY/PRINCIPAL FINDINGS: To identify genes and molecular functions
      transcriptionally affected by gamma-secretase activity, the cellular
      transcriptomes of Chinese hamster ovary (CHO) cells with enhanced and inhibited
      gamma-secretase activity were analyzed and compared by cDNA microarray. The
      functional clustering by FatiGO of the 1,981 identified genes revealed over- and
      under-represented groups with multiple activities and functions. Single genes
      with the most pronounced transcriptional susceptibility to gamma-secretase
      activity were evaluated by real-time PCR. Among the 21 validated genes, the
      strikingly decreased transcription of PTPRG and AMN1 and increased transcription
      of UPP1 potentially support data on cell cycle disturbances relevant to cancer,
      stem cell and neurodegenerative diseases' research. The mapping of interactions
      of proteins encoded by the validated genes exclusively relied on evidence-based
      data and revealed broad effects on Wnt pathway members, including WNT3A and DVL3.
      Intriguingly, the transcription of TERA, a gene of unknown function, is affected
      by gamma-secretase activity and was significantly altered in the analyzed human
      Alzheimer's disease brain cortices. CONCLUSIONS/SIGNIFICANCE: Investigating the
      effects of gamma-secretase activity on gene transcription has revealed several
      affected clusters of molecular functions and, more specifically, 21 genes that
      hold significant potential for a better understanding of the biology of gamma
      secretase and its roles in cancer and Alzheimer's disease pathology.

PMID- 19763260
TI  - Two factor reprogramming of human neural stem cells into pluripotency.
AB  - BACKGROUND: Reprogramming human somatic cells to pluripotency represents a
      valuable resource for the development of in vitro based models for human disease
      and holds tremendous potential for deriving patient-specific pluripotent stem
      cells. Recently, mouse neural stem cells (NSCs) have been shown capable of
      reprogramming into a pluripotent state by forced expression of Oct3/4 and Klf4;
      however it has been unknown whether this same strategy could apply to human NSCs,
      which would result in more relevant pluripotent stem cells for modeling human
      disease. METHODOLOGY AND PRINCIPAL FINDINGS: Here, we show that OCT3/4 and KLF4
      are indeed sufficient to induce pluripotency from human NSCs within a two week
      time frame and are molecularly indistinguishable from human ES cells.
      Furthermore, human NSC-derived pluripotent stem cells can differentiate into all
      three germ lineages both in vitro and in vivo. CONCLUSIONS/SIGNIFICANCE: We
      propose that human NSCs represent an attractive source of cells for producing
      human iPS cells since they only require two factors, obviating the need for c
      MYC, for induction into pluripotency. Thus, in vitro human disease models could
      be generated from iPS cells derived from human NSCs.

PMID- 19763261
TI  - Empirical study of data sharing by authors publishing in PLoS journals.
AB  - BACKGROUND: Many journals now require authors share their data with other
      investigators, either by depositing the data in a public repository or making it
      freely available upon request. These policies are explicit, but remain largely
      untested. We sought to determine how well authors comply with such policies by
      requesting data from authors who had published in one of two journals with clear
      data sharing policies. METHODS AND FINDINGS: We requested data from ten
      investigators who had published in either PLoS Medicine or PLoS Clinical Trials.
      All responses were carefully documented. In the event that we were refused data,
      we reminded authors of the journal's data sharing guidelines. If we did not
      receive a response to our initial request, a second request was made. Following
      the ten requests for raw data, three investigators did not respond, four authors
      responded and refused to share their data, two email addresses were no longer
      valid, and one author requested further details. A reminder of PLoS's explicit
      requirement that authors share data did not change the reply from the four
      authors who initially refused. Only one author sent an original data set.
      CONCLUSIONS: We received only one of ten raw data sets requested. This suggests
      that journal policies requiring data sharing do not lead to authors making their
      data sets available to independent investigators.

PMID- 19763262
TI  - Behaviourally mediated phenotypic selection in a disturbed coral reef
      environment.
AB  - Natural and anthropogenic disturbances are leading to changes in the nature of
      many habitats globally, and the magnitude and frequency of these perturbations
      are predicted to increase under climate change. Globally coral reefs are one of
      the most vulnerable ecosystems to climate change. Fishes often show relatively
      rapid declines in abundance when corals become stressed and die, but the
      processes responsible are largely unknown. This study explored the mechanism by
      which coral bleaching may influence the levels and selective nature of mortality
      on a juvenile damselfish, Pomacentrus amboinensis, which associates with hard
      coral. Recently settled fish had a low propensity to migrate small distances (40
      cm) between habitat patches, even when densities were elevated to their natural
      maximum. Intraspecific interactions and space use differ among three habitats:
      live hard coral, bleached coral and dead algal-covered coral. Large fish pushed
      smaller fish further from the shelter of bleached and dead coral thereby exposing
      smaller fish to higher mortality than experienced on healthy coral. Small
      recruits suffered higher mortality than large recruits on bleached and dead
      coral. Mortality was not size selective on live coral. Survival was 3 times as
      high on live coral as on either bleached or dead coral. Subtle behavioural
      interactions between fish and their habitats influence the fundamental link
      between life history stages, the distribution of phenotypic traits in the local
      population and potentially the evolution of life history strategies.

PMID- 19763263
TI  - Novel mitochondrial substrates of omi indicate a new regulatory role in
      neurodegenerative disorders.
AB  - The mitochondrial protease OMI (also known as HtrA2) has been implicated in
      Parkinson's Disease (PD) and deletion or protease domain point mutations have
      shown profound neuropathologies in mice. A beneficial role by OMI, in preserving
      cell viability, is assumed to occur via the avoidance of dysfunctional protein
      turnover. However relatively few substrates for mitochondrial Omi are known. Here
      we report our identification of three novel mitochondrial substrates that impact
      metabolism and ATP production. Using a dual proteomic approach we have identified
      three interactors based upon ability to bind to OMI, and/or to persist in the
      proteome after OMI activity has been selectively inhibited. One candidate, the
      chaperone HSPA8, was common to each independent study. Two others (PDHB subunit
      and IDH3A subunit) did not appear to bind to OMI, however persisted in the mito
      proteome when OMI was inhibited. Pyruvate dehydrogenase (PDH) and isocitrate
      dehydrogenase (IDH) are two key Kreb's cycle enzymes that catalyse oxidative
      decarboxylation control points in mitochondrial respiration. We verified both
      PDHB and IDH3A co-immunoprecipitate with HSPA8 and after elution, were degraded
      by recombinant HtrA2 in vitro. Additionally our gene expression studies, using
      rotenone (an inhibitor of Complex I) showed Omi expression was silenced when pdhb
      and idh3a were increased when a sub-lethal dose was applied. However higher dose
      treatment caused increased Omi expression and decreased levels of pdhb and idh3a
      transcripts. This implicates mitochondrial OMI in a novel mechanism relating to
      metabolism.

PMID- 19763264
TI  - Development and validation of a real-time PCR for detection of pathogenic
      leptospira species in clinical materials.
AB  - Available serological diagnostics do not allow the confirmation of clinically
      suspected leptospirosis at the early acute phase of illness. Several conventional
      and real-time PCRs for the early diagnosis of leptospirosis have been described
      but these have been incompletely evaluated. We developed a SYBR Green-based real
      time PCR targeting secY and validated it according to international guidelines.
      To determine the analytical specificity, DNA from 56 Leptospira strains belonging
      to pathogenic, non-pathogenic and intermediate Leptospira spp. as well as 46
      other micro-organisms was included in this study. All the pathogenic Leptospira
      gave a positive reaction. We found no cross-reaction with saprophytic Leptospira
      and other micro-organisms, implying a high analytical specificity. The analytical
      sensitivity of the PCR was one copy per reaction from cultured homologous strain
      M 20 and 1.2 and 1.5 copy for heterologous strains 1342 K and Sarmin,
      respectively. In spiked serum & blood and kidney tissue the sensitivity was 10
      and 20 copies for M 20, 15 and 30 copies for 1342 K and 30 and 50 copies for
      Sarmin. To determine the diagnostic sensitivity (DSe) and specificity (DSp),
      clinical blood samples from 26 laboratory-confirmed and 107 negative patients
      suspected of leptospirosis were enrolled as a prospective consecutive cohort.
      Based on culture as the gold standard, we found a DSe and DSp of 100% and 93%,
      respectively. All eight PCR positive samples that had a negative culture
      seroconverted later on, implying a higher actual DSp. When using culture and
      serology as the gold standard, the DSe was lower (89%) while the DSp was higher
      (100%). DSe was 100% in samples collected within the first--for treatment
      important--4 days after onset of the illness. Reproducibility and repeatability
      of the assay, determined by blind testing kidney samples from 20 confirmed
      positive and 20 negative rodents both appeared 100%. In conclusion we have
      described for the first time the development of a robust SYBR Green real-time PCR
      for the detection of pathogenic Leptospira combined with a detailed assessment of
      its clinical accuracy, thus providing a method for the early diagnosis of
      leptospirosis with a well-defined satisfactory performance.

PMID- 19763265
TI  - Disturbance alters the phylogenetic composition and structure of plant
      communities in an old field system.
AB  - The changes in phylogenetic composition and structure of communities during
      succession following disturbance can give us insights into the forces that are
      shaping communities over time. In abandoned agricultural fields, community
      composition changes rapidly when a field is plowed, and is thought to reflect a
      relaxation of competition due to the elimination of dominant species which take
      time to re-establish. Competition can drive phylogenetic overdispersion, due to
      phylogenetic conservation of 'niche' traits that allow species to partition
      resources. Therefore, undisturbed old field communities should exhibit higher
      phylogenetic dispersion than recently disturbed systems, which should be
      relatively 'clustered' with respect to phylogenetic relationships. Several
      measures of phylogenetic structure between plant communities were measured in
      recently plowed areas and nearby 'undisturbed' sites. There was no difference in
      the absolute values of these measures between disturbed and 'undisturbed' sites.
      However, there was a difference in the 'expected' phylogenetic structure between
      habitats, leading to significantly lower than expected phylogenetic diversity in
      disturbed plots, and no difference from random expectation in 'undisturbed'
      plots. This suggests that plant species characteristic of each habitat are fairly
      evenly distributed on the shared species pool phylogeny, but that once the
      initial sorting of species into the two habitat types has occurred, the processes
      operating on them affect each habitat differently. These results were consistent
      with an analysis of correlation between phylogenetic distance and co-occurrence
      indices of species pairs in the two habitat types. This study supports the notion
      that disturbed plots are more clustered than expected, rather than 'undisturbed'
      plots being more overdispersed, suggesting that disturbed plant communities are
      being more strongly influenced by environmental filtering of conserved niche
      traits.

PMID- 19763266
TI  - Proteomic interrogation of androgen action in prostate cancer cells reveals roles
      of aminoacyl tRNA synthetases.
AB  - Prostate cancer remains the most common malignancy among men in United States,
      and there is no remedy currently available for the advanced stage hormone
      refractory cancer. This is partly due to the incomplete understanding of androgen
      regulated proteins and their encoded functions. Whole-cell proteomes of androgen
      starved and androgen-treated LNCaP cells were analyzed by semi-quantitative
      MudPIT ESI- ion trap MS/MS and quantitative iTRAQ MALDI- TOF MS/MS platforms,
      with identification of more than 1300 high-confidence proteins. An enrichment
      based pathway mapping of the androgen-regulated proteomic data sets revealed a
      significant dysregulation of aminoacyl tRNA synthetases, indicating an increase
      in protein biosynthesis- a hallmark during prostate cancer progression. This
      observation is supported by immunoblot and transcript data from LNCaP cells, and
      prostate cancer tissue. Thus, data derived from multiple proteomics platforms and
      transcript data coupled with informatics analysis provides a deeper insight into
      the functional consequences of androgen action in prostate cancer.

PMID- 19763267
TI  - Cell cycle-related cyclin b1 quantification.
AB  - BACKGROUND: To obtain non-relative measures of cell proteins, purified
      preparations of the same proteins are used as standards in Western blots. We have
      previously quantified SV40 large T antigen expressed over a several fold range in
      different cell lines and correlated the average number of molecules to average
      fluorescence obtained by cytometry and determined cell cycle phase related
      expression by calculation from multi-parametric cytometry data. Using a modified
      approach, we report quantification of endogenous cyclin B1 and generation of the
      cell cycle time related expression profile. METHODOLOGY: Recombinant cyclin B1
      was purified from a baculovirus lysate using an antibody affinity column and
      concentrated. We created fixed cell preparations from nocodazole-treated (high
      cyclin B1) and serum starved (low cyclin B1) PC3 cells that were either
      lyophilized (for preservation) or solubilized. The lysates and purified cyclin B1
      were subjected to Western blotting; the cell preparations were subjected to
      cytometry, and fluorescence was correlated to molecules. Three untreated cell
      lines (K562, HeLa, and RKO) were prepared for cytometry without lyophilization
      and also prepared for Western blotting. These were quantified by Western blotting
      and by cytometry using the standard cell preparations. RESULTS: The standard cell
      preparations had 1.5 x 10(5) to 2.5 x 10(6) molecules of cyclin B1 per cell on
      average (i.e., 16-fold range). The average coefficient of variation was 24%.
      Fluorescence varied 12-fold. The relationship between molecules/cell (Western
      blot) and immunofluorescence (cytometry) was linear (r(2) = 0.87). Average cyclin
      B1 levels for the three untreated cell lines determined by Western blotting and
      cytometry agreed within a factor of 2. The non-linear rise in cyclin B1 in S
      phase was quantified from correlated plots of cyclin B1 and DNA content. The peak
      levels achieved in G2 were similar despite differences in lineage, growth
      conditions, and rates of increase through the cell cycle (range: 1.6-2.2 x 10(6)
      molecules per cell). CONCLUSIONS: Net cyclin B1 expression begins in G1 in human
      somatic cells lines; increases non-linearly with variation in rates of
      accumulation, but peaks at similar peak values in different cell lines growing
      under different conditions. This suggests tight quantitative end point control.

PMID- 19763268
TI  - Alternative-splicing in the exon-10 region of GABA(A) receptor beta(2) subunit
      gene: relationships between novel isoforms and psychotic disorders.
AB  - BACKGROUND: Non-coding single nucleotide polymorphisms (SNPs) in GABRB2, the gene
      for beta(2)-subunit of gamma-aminobutyric acid type A (GABA(A)) receptor, have
      been associated with schizophrenia (SCZ) and quantitatively correlated to mRNA
      expression and alternative splicing. METHODS AND FINDINGS: Expression of the Exon
      10 region of GABRB2 from minigene constructs revealed this region to be an
      "alternative splicing hotspot" that readily gave rise to differently spliced
      isoforms depending on intron sequences. This led to a search in human brain cDNA
      libraries, and the discovery of two novel isoforms, beta(2S1) and beta(2S2),
      bearing variations in the neighborhood of Exon-10. Quantitative real-time PCR
      analysis of postmortem brain samples showed increased beta(2S1) expression and
      decreased beta(2S2) expression in both SCZ and bipolar disorder (BPD) compared to
      controls. Disease-control differences were significantly correlated with SNP
      rs187269 in BPD males for both beta(2S1) and beta(2S2) expressions, and
      significantly correlated with SNPs rs2546620 and rs187269 in SCZ males for
      beta(2S2) expression. Moreover, site-directed mutagenesis indicated that
      Thr(365), a potential phosphorylation site in Exon-10, played a key role in
      determining the time profile of the ATP-dependent electrophysiological current
      run-down. CONCLUSION: This study therefore provided experimental evidence for the
      importance of non-coding sequences in the Exon-10 region in GABRB2 with respect
      to beta(2)-subunit splicing diversity and the etiologies of SCZ and BPD.

PMID- 19763269
TI  - Escape from autologous neutralizing antibodies in acute/early subtype C HIV-1
      infection requires multiple pathways.
AB  - One aim for an HIV vaccine is to elicit neutralizing antibodies (Nab) that can
      limit replication of genetically diverse viruses and prevent establishment of a
      new infection. Thus, identifying the strengths and weaknesses of Nab during the
      early stages of natural infection could prove useful in achieving this goal. Here
      we demonstrate that viral escape readily occurred despite the development of high
      titer autologous Nab in two subjects with acute/early subtype C infection. To
      provide a detailed portrayal of the escape pathways, Nab resistant variants
      identified at multiple time points were used to create a series of envelope (Env)
      glycoprotein chimeras and mutants within the background of a corresponding newly
      transmitted Env. In one subject, Nab escape was driven predominantly by changes
      in the region of gp120 that extends from the beginning of the V3 domain to the
      end of the V5 domain (V3V5). However, Nab escape pathways in this subject
      oscillated and at times required cooperation between V1V2 and the gp41
      ectodomain. In the second subject, escape was driven by changes in V1V2. This
      V1V2-dependent escape pathway was retained over time, and its utility was
      reflected in the virus's ability to escape from two distinct monoclonal
      antibodies (Mabs) derived from this same patient via introduction of a single
      potential N-linked glycosylation site in V2. Spatial representation of the
      sequence changes in gp120 suggested that selective pressure acted upon the same
      regions of Env in these two subjects, even though the Env domains that drove
      escape were different. Together the findings argue that a single mutational
      pathway is not sufficient to confer escape in early subtype C HIV-1 infection,
      and support a model in which multiple strategies, including potential glycan
      shifts, direct alteration of an epitope sequence, and cooperative Env domain
      conformational masking, are used to evade neutralization.

PMID- 19763270
TI  - Transcriptional signature and memory retention of human-induced pluripotent stem
      cells.
AB  - Genetic reprogramming of somatic cells to a pluripotent state (induced
      pluripotent stem cells or iPSCs) by over-expression of specific genes has been
      accomplished using mouse and human cells. However, it is still unclear how
      similar human iPSCs are to human Embryonic Stem Cells (hESCs). Here, we describe
      the transcriptional profile of human iPSCs generated without viral vectors or
      genomic insertions, revealing that these cells are in general similar to hESCs
      but with significant differences. For the generation of human iPSCs without viral
      vectors or genomic insertions, pluripotent factors Oct4 and Nanog were cloned in
      episomal vectors and transfected into human fetal neural progenitor cells. The
      transient expression of these two factors, or from Oct4 alone, resulted in
      efficient generation of human iPSCs. The reprogramming strategy described here
      revealed a potential transcriptional signature for human iPSCs yet retaining the
      gene expression of donor cells in human reprogrammed cells free of viral and
      transgene interference. Moreover, the episomal reprogramming strategy represents
      a safe way to generate human iPSCs for clinical purposes and basic research.

PMID- 19763271
TI  - Limited neutralizing antibody specificities drive neutralization escape in early
      HIV-1 subtype C infection.
AB  - We previously showed that HIV-1 subtype C viruses elicit potent but highly type
      specific neutralizing antibodies (nAb) within the first year of infection. In
      order to determine the specificity and evolution of these autologous nAbs, we
      examined neutralization escape in four individuals whose responses against the
      earliest envelope differed in magnitude and potency. Neutralization escape
      occurred in all participants, with later viruses showing decreased sensitivity to
      contemporaneous sera, although they retained sensitivity to new nAb responses.
      Early nAb responses were very restricted, occurring sequentially and targeting
      only two regions of the envelope. In V1V2, limited amino acid changes often
      involving indels or glycans, mediated partial or complete escape, with nAbs
      targeting the V1V2 region directly in 2 cases. The alpha-2 helix of C3 was also a
      nAb target, with neutralization escape associated with changes to positively
      charged residues. In one individual, relatively high titers of anti-C3 nAbs were
      required to drive genetic escape, taking up to 7 weeks for the resistant variant
      to predominate. Thereafter titers waned but were still measurable. Development of
      this single anti-C3 nAb specificity was associated with a 7-fold drop in HIV-1
      viral load and a 4-fold rebound as the escape mutation emerged. Overall, our data
      suggest the development of a very limited number of neutralizing antibody
      specificities during the early stages of HIV-1 subtype C infection, with temporal
      fluctuations in specificities as escape occurs. While the mechanism of
      neutralization escape appears to vary between individuals, the involvement of
      limited regions suggests there might be common vulnerabilities in the HIV-1
      subtype C transmitted envelope.

PMID- 19763272
TI  - Caveolae contribute to the apoptosis resistance induced by the alpha(1A)
      adrenoceptor in androgen-independent prostate cancer cells.
AB  - BACKGROUND: During androgen ablation prostate cancer cells' growth and survival
      become independent of normal regulatory mechanisms. These androgen-independent
      cells acquire the remarkable ability to adapt to the surrounding microenvironment
      whose factors, such as neurotransmitters, influence their survival. Although
      findings are becoming evident about the expression of alpha(1A)-adrenoceptors in
      prostate cancer epithelial cells, their exact functional role in androgen
      independent cells has yet to be established. Previous work has demonstrated that
      membrane lipid rafts associated with key signalling proteins mediate growth and
      survival signalling pathways in prostate cancer cells. METHODOLOGY/PRINCIPAL
      FINDINGS: In order to analyze the membrane topology of the alpha(1A)-adrenoceptor
      we explored its presence by a biochemical approach in purified detergent
      resistant membrane fractions of the androgen-independent prostate cancer cell
      line DU145. Electron microscopy observations demonstrated the colocalization of
      the alpha(1A)-adrenoceptor with caveolin-1, the major protein component of
      caveolae. In addition, we showed that agonist stimulation of the alpha(1A)
      adrenoceptor induced resistance to thapsigargin-induced apoptosis and that
      caveolin-1 was necessary for this process. Further, immunohistofluorescence
      revealed the relation between high levels of alpha(1A)-adrenoceptor and caveolin
      1 expression with advanced stage prostate cancer. We also show by immunoblotting
      that the TG-induced apoptosis resistance described in DU145 cells is mediated by
      extracellular signal-regulated kinases (ERK). CONCLUSIONS/SIGNIFICANCE: In
      conclusion, we propose that alpha(1A)-adrenoceptor stimulation in androgen
      independent prostate cancer cells via caveolae constitutes one of the mechanisms
      contributing to their protection from TG-induced apoptosis.

PMID- 19763273
TI  - The cat and mouse of HIV-1 antibody escape.

PMID- 19763274
TI  - Time-resolved transcriptome analysis of Bacillus subtilis responding to valine,
      glutamate, and glutamine.
AB  - Microorganisms can restructure their transcriptional output to adapt to
      environmental conditions by sensing endogenous metabolite pools. In this paper,
      an Agilent customized microarray representing 4,106 genes was used to study
      temporal transcript profiles of Bacillus subtilis in response to valine,
      glutamate and glutamine pulses over 24 h. A total of 673, 835, and 1135 amino
      acid-regulated genes were identified having significantly changed expression at
      one or more time points in response to valine, glutamate, and glutamine,
      respectively, including genes involved in cell wall, cellular import, metabolism
      of amino-acids and nucleotides, transcriptional regulation, flagellar motility,
      chemotaxis, phage proteins, sporulation, and many genes of unknown function.
      Different amino acid treatments were compared in terms of both the global
      temporal profiles and the 5-minute quick regulations, and between-experiment
      differential genes were identified. The highlighted genes were analyzed based on
      diverse sources of gene functions using a variety of computational tools,
      including T-profiler analysis, and hierarchical clustering. The results revealed
      the common and distinct modes of action of these three amino acids, and should
      help to elucidate the specific signaling mechanism of each amino acid as an
      effector.

PMID- 19763275
TI  - VEGFR1 activity modulates myeloid cell infiltration in growing lung metastases
      but is not required for spontaneous metastasis formation.
AB  - The role of vascular endothelial growth factor receptor 1 (VEGFR1/Flt1) in tumor
      metastasis remains incompletely characterized. Recent reports suggested that
      blocking VEGFR1 activity or the interaction with its ligands (VEGF and PlGF) has
      anti-tumor effects. Moreover, several studies showed that VEGFR1 mediates tumor
      progression to distant metastasis. All these effects may be exerted indirectly by
      recruitment of bone marrow-derived cells (BMDCs), such as myeloid cells. We
      investigated the role of VEGFR1 activity in BMDCs during the pre-metastatic
      phase, i.e., prior to metastatic nodule formation in mice after surgical removal
      of the primary tumor. Using pharmacologic blockade or genetic deletion of the
      tyrosine kinase domain of VEGFR1, we demonstrate that VEGFR1 activity is not
      required for the infiltration of de novo myeloid BMDCs in the pre-metastatic
      lungs in two tumor models and in two mouse models. Moreover, in line with
      emerging clinical observations, we show that blockade of VEGFR1 activity neither
      prevents nor changes the rate of spontaneous metastasis formation after primary
      tumor removal. Prevention of metastasis will require further identification and
      exploration of cellular and molecular pathways that mediate the priming of the
      metastatic soil.

PMID- 19763276
TI  - Alterations in adenylate kinase activity in human PBMCs after in vitro exposure
      to electromagnetic field: comparison between extremely low frequency
      electromagnetic field (ELF) and therapeutic application of a musically modulated
      electromagnetic field (TAMMEF).
AB  - This study investigated the effects of electromagnetic fields on enzymes involved
      in purine metabolism in human peripheral blood mononuclear cells in vitro. Cells
      were obtained from 20 volunteers. We tested both low-energy, extremely low
      frequency (ELF; 100-Hz) electromagnetic fields and the Therapeutic Application of
      Musically Modulated Electromagnetic Fields (TAMMEFs); the latter is characterized
      by variable frequencies, intensities, and wave shapes. Adenylate kinase activity
      was increased after ELF field exposure but decreased slightly after TAMMEF
      exposure. Neither of the two electromagnetic field affected the activities of the
      purine metabolism enzymes ecto-5'-nucleotidase, adenosine deaminase, and
      adenosine kinase. We concluded that ELF fields may influence cellular electrical
      charge stability; stimulation of adenylate kinase activity could restore the cell
      to a state of equilibrium. In contrast, TAMMEF fields may be useful for
      maintaining and regulating the cellular electrical charge.

PMID- 19763277
TI  - HBX-mediated migration of HBV-replicating HepG2 cells: insights on development of
      hepatocellular carcinoma.
AB  - Hepatitus B virus (HBV) is a major cause of the development of hepatpcellular
      carcinoma (HCC). One of the significant characteristics of tumor progression is
      cell migration which is reflective of cytoskeletal dynamics. The Rho GTPases
      contribute to a multiple cellular processes, including the cellular cytoskeletal
      reorganization and motility. It has been found that some Rho GTPases have
      oncogenic activity and can promote cancer cell invasion. Here we discuss one of
      the Rho GTPases, Rac1 can be activated by HBV replication and such activation
      results in the high motility of HBV-replicating cells. The enhanced cell motility
      can be interestingly alleviated by the mutation at the sites of proline rich
      domain located in HBX. Our findings may provide new insights on the mechanism of
      HCC development associated with chronic HBV infection.

PMID- 19763278
TI  - The effects of maturation on the colonic microflora in infancy and childhood.
AB  - The composition of colonic mircoflora and its changes with maturation have rarely
      been investigated in large samples. Methods. We used conventional microbiological
      testing to analyse the colonic flora (Kyberstatus, Institut forMicroecology,
      Herborn, Germany) of stool samples from 12 484 children with different intestinal
      and nonintestinal diagnoses. Stool samples were analysed for total colony forming
      units (CFU) (per g stool) and the abundance of Bifidobacteria, Bacteroides sp.,
      Escherichia coli, Enterococcus sp., and Lactobacillus sp. with respect to age,
      gender. A subset of 1089 infants was analysed for monthly changes within the
      first year of life. Results. Total CFU and individual microbial species were
      highest during the first year of life, decreased within the first 2 years, and
      then stabilized for the remaining childhood. In infants, the total CFU rose until
      month 5, declined with weaning, and peaked at 9-10 months. Significant effects of
      age, but not of gender, were found in Bacteroides sp. and Lactobacilli. However
      Bacterioids sp. and Lactobacilli increased with age, while Enterococci and E.
      coli decreased, and Bifidobacteria remained stable. Conclusion. Colonic
      microflora show both a bacteria-specific and general pattern of maturation which
      is most profound within the first year.

PMID- 19763279
TI  - Open-Label Study of Craving in Smokers With Schizophrenia Using Nicotine Nasal
      Spray Compared to Nicotine Patch.
AB  - RATIONALE: Nicotine nasal spray (NNS) may be better for relieving acute cigarette
      cravings than other nicotine replacement and it may help smokers with
      schizophrenia because of its rapid onset of action. OBJECTIVES: We tested whether
      NNS was more effective than a nicotine patch (NP; 21 mg) in reducing cue-induced
      craving during a 3-day abstinence. METHODS: Twenty-five smokers with
      schizophrenia or schizoaffective disorder (SA) were randomized to open-label NNS
      or NP treatment after baseline measures of craving were assessed. NNS users were
      instructed to dose at a minimum of 1/hour and up to a maximum of 40/day. Averages
      from a 4-item visual analogue scale (need, urge, want to smoke, crave a
      cigarette) measured craving. RESULTS: Five subjects who smoked (4 NP, 1 NNS) were
      excluded, leaving 21 (11 NP, 10 NNS) for analyses. No differences were detected
      between groups on baseline craving. On day 3, NNS users reported significantly
      less craving in response to smoking cues compared to NP users (mean craving
      scores: NNS, 7.0; NP, 20.3; p = .014). A repeated measure ANCOVA demonstrated
      significantly reduced craving in the NNS group compared to the NP group from
      baseline to day 3 (F = 5.09; p = .037). NNS users took an average of 20
      doses/day, and NNS was rated as being as easy to use as NP. CONCLUSIONS: The
      potential utility of NNS in smokers with schizophrenia supports the need for
      placebo-controlled studies.

PMID- 19763280
TI  - The Implications of the Cancer Stem Cell Hypothesis for Neuro-Oncology and
      Neurology.
AB  - The cancer stem cell hypothesis posits that cancers contain a subset of
      neoplastic cells that propagate and maintain tumors through sustained self
      renewal and potent tumorigenecity. Recent excitement has been generated by a
      number of reports that have demonstrated the existence of cancer stem cells in
      several types of brain tumors. Brain cancer stem cells - also called tumor
      initiating cells or tumor propagating cells - share features with normal neural
      stem cells but do not necessarily originate from stem cells. Although most
      cancers have only a small fraction of cancer stem cells, these tumor cells have
      been shown in laboratory studies to contribute to therapeutic resistance,
      formation of new blood vessels to supply the tumor, and tumor spread. As
      malignant brain tumors rank among the deadliest of all neurologic diseases, the
      identification of new cellular targets may have profound implications in neuro
      oncology. Novel drugs that target stem cell pathways active in brain tumors have
      been efficacious against cancer stem cells suggesting that anti-cancer stem cell
      therapies may advance brain tumor therapy. The cancer stem cell hypothesis may
      have several implications for other neurologic diseases as caution must be
      exercised in activating stem cell maintenance pathways in cellular therapies for
      neurodegenerative diseases. The ability for a small fraction of cells to
      determine the overall course of a disease may also inform new paradigms of
      disease that may translate into improved patient outcomes.

PMID- 19763281
TI  - Chasing lipids in health and diseases by coherent anti-Stokes Raman scattering
      microscopy.
AB  - The integration of near IR picosecond pulse excitation, collinear beam geometry,
      epi-detection, and laser-scanning has produced a coherent anti-Stokes Raman
      scattering (CARS) microscope with a detection sensitivity of 10(5) vibrational
      oscillators, sub-micron 3D resolution, and video-rate acquisition speed. The
      incorporation of spectral detection and other imaging modalities has added
      versatility to the CARS microscope. These advances allowed sensitive
      interrogation of biological samples, particularly lipids that have a high density
      of CH(2) groups. With initial applications to membrane domains, lipid bodies,
      demyelinating diseases, obesity, and cardiovascular diseases, CARS microscopy is
      poised to become a powerful bio-imaging tool with the availability of a
      multifunctional, affordable, easy-to-operate CARS microscope, and the development
      of CARS endoscopy for in vivo diagnosis.

PMID- 19763282
TI  - GENDER DIFFERENCES IN PERCEPTIONS OF SEXUAL INTENT: A QUALITATIVE REVIEW AND
      INTEGRATION.
AB  - Men appear to interpret people's behaviors more sexually than do women. This
      finding, which has been replicated in scores of studies using a variety of
      methodological approaches, has been linked to important social concerns,
      including sexual assault and sexual harassment. This article provides a critical
      review of the published literature on gender differences in sexual intent
      perception, using selective examples to illustrate and summarize the field's
      major constructs, methodologies, and empirical findings. Theoretical explanations
      for gender differences in sexual intent perceptions are reviewed. Finally, we
      highlight the field's remaining issues and make several recommendations for
      future research directions.

PMID- 19763283
TI  - The Support Reduction Algorithm for Computing Non-Parametric Function Estimates
      in Mixture Models.
AB  - In this paper, we study an algorithm (which we call the support reduction
      algorithm) that can be used to compute non-parametric M-estimators in mixture
      models. The algorithm is compared with natural competitors in the context of
      convex regression and the 'Aspect problem' in quantum physics.

PMID- 19763287
TI  - Molecular playdough: conformationally programmable molecular receptors based on
      restricted rotation.
AB  - A new method for rapidly tailoring molecular properties is presented in which the
      three-dimensional shape of a malleable framework is controlled by heating with a
      template molecule.

PMID- 19763288
TI  - Ruthenium-catalyzed selective N ,N-diallylation- and N ,N ,O-triallylation of
      free amino acids.
AB  - Selective N ,N-diallylation and N ,N, O-triallylation of free amino acids in the
      presence of catalytic amounts of RuCp*(MeCN)(3)PF(6) is reported. The crucial
      influence of the solvent makes these allylation reactions selectively possible.

PMID- 19763289
TI  - Single and dual glycoside clustering around calix[4]arene scaffolds via click
      thiol-ene coupling and azide-alkyne cycloaddition.
AB  - We present the first synthesis of calix[4]arene-based S-glycoclusters via
      photoinduced multiple thiol-ene coupling of tetra- and octa-allyl calix[4]arenes
      with peracetylated glucosyl thiol (67-88% yields). Moreover we describe the dual
      clustering at the upper and lower rim of a calix[4]arene with two different
      sugars (galactose and glucose) via sequential copper(i)-catalyzed azide-alkyne
      cycloaddition and photoinduced thiol-ene coupling.

PMID- 19763290
TI  - Enantioselective synthesis of pure (R,R)-2,3-butanediol in Escherichia coli with
      stereospecific secondary alcohol dehydrogenases.
AB  - We characterized the activity and stereospecificity of four secondary alcohol
      dehydrogenases (sADHs) towards acetoin reduction and constructed synthetic
      pathways in E. coli to produce enantiomerically pure (R,R)-2,3-butanediol (2,3
      BDO) from glucose with a titer of 6.1 g/L (enantio purity >99%), and yield of
      0.31 g product/g glucose (62% of theoretical maximum).

PMID- 19763291
TI  - Diastereoselective addition of sugar radicals to camphorsultam glyoxilic oxime
      ether: a route toward C-glycosylthreonine and allothreonine.
AB  - C-glucosyl, mannosyl and galactosyl 2-iodopropane, readily obtained from the
      corresponding C-glycosyl ketones, were coupled with (+)- or (-)-camphorsultam
      glyoxylic oxime ether with diastereoselectivity ranging from 70:30 to 80:20. C
      glucosyl allothreonine was obtained by cleavage of the camphorsultam moiety.

PMID- 19763292
TI  - Nickel-catalyzed cross-coupling of diarylamines with haloarenes.
AB  - The cross-coupling reaction of diarylamines with aryl bromides/iodides can be
      effected by the Ni(ii)-(sigma-aryl) complex/PPh(3)/NaH system, and a preliminary
      investigation was conducted into the mechanism of this reaction.

PMID- 19763293
TI  - Unconventional hydrogen-bond-directed hierarchical co-assembly between perylene
      bisimide and azobenzene-functionalized melamine.
AB  - Co-assembly of ditopic perylene bisimide and azobenzene-functionalized melamine
      occurs with an unconventional stoichiometric ratio, providing well-defined
      nanostructures with a helically-coiled architecture where perylene chromophores
      are packed in desirable J-type arrangements.

PMID- 19763294
TI  - Light-driven molecular switches with tetrahedral and axial chirality.
AB  - Two light-driven molecular switches with tetrahedral and axial chirality were
      synthesized, which can induce a helical superstructure in an achiral liquid
      crystal host and dynamically phototune it to achieve reversible reflection color.

PMID- 19763295
TI  - A new assay format for NF-kappaB based on a DNA triple helix and a fluorescence
      resonance energy transfer.
AB  - Herein we report a feasibility study for a new concept to detect DNA binding
      protein NF-kappaB based on a DNA triple helix formation in combination with a
      fluorescence resonance energy transfer (FRET). The new principle avoids expensive
      antibodies and radioactivity and might have implications for assays of other DNA
      binding proteins.

PMID- 19763296
TI  - A gorge-spanning, high-affinity cholinesterase inhibitor to explore beta-amyloid
      plaques.
AB  - Cholinesterases are involved in the pathological formation of beta-amyloid
      plaques. To investigate this pathohistological hallmark of Alzheimer's disease we
      prepared a high-affinity, fluorescent cholinesterase inhibitor. Its fluorescence
      intensity was significantly enhanced upon binding to cholinesterases. Using this
      probe, brain samples from mice and humans affected by Alzheimer's disease were
      successfully analyzed for beta-amyloid plaques. Unexpectedly, it was discovered,
      by competition experiments, that the compound binds to amyloid structures, rather
      than to cholinesterases inside of the plaques.

PMID- 19763297
TI  - New organofluorine building blocks: inhibition of the malarial aspartic proteases
      plasmepsin II and IV by alicyclic alpha,alpha-difluoroketone hydrates.
AB  - The development of new therapeutic agents against malaria has become urgent
      during the past few decades, due to an increased prevalence of drug-resistant
      strains of malaria-causing Plasmodium parasites. Possible targets are the
      hemoglobin-degrading aspartic proteases, the plasmepsins. While acyclic
      alpha,alpha-difluoroketone hydrates have been introduced into peptidomimetics to
      bind to the catalytic Asp dyad of aspartic proteases, alicyclic derivatives were
      unknown. This paper describes a versatile synthesis of hydrated alicyclic
      alpha,alpha-difluoro-cyclopentanones and -cyclohexanones, decorated with
      appropriate substituents to fill the S1/S3 and the "flap-open" pocket at the
      enzyme active sites. Their biological activity was tested against plasmepsin II
      and IV, revealing an IC(50) value (concentration of an inhibitor at which 50%
      maximum initial velocity is observed) of 7 microM for the best ligand. Reference
      inhibitors with a protonated secondary ammonium centre to address the catalytic
      dyad showed similar binding affinities. The X-ray crystal structure of a cyclic
      alpha,alpha-difluoroketone hydrate revealed the ability of these novel building
      blocks to participate in H-bonding networks. The hydration of difluoroketones was
      also investigated in solution. An exemplary study showed that the equilibrium
      constants for the hydration of alpha,alpha-difluorinated cyclohexanones are much
      higher than those for the corresponding cyclopentanones.

PMID- 19763298
TI  - Microwave-assisted synthesis of a new series of resorcin[4]arene cavitand-capped
      porphyrin capsules.
AB  - Capsule-shaped molecular receptors are fundamental to the modeling of biological
      host-guest interactions such as those characteristic of enzymatic processes.
      Among the more versatile and effective synthetic receptors are the hemicarcerand
      type hosts. Herein we report the synthesis of six novel resorcin[4]arene cavitand
      capped porphyrin capsules, in a new series of molecular capsules modeled on the
      classical hemicarcerands initially reported by Cram and co-workers. In the first
      reported instance of its utilisation in the preparation of supramolecularly
      capped porphyrin host molecules, microwave (MW) irradiation was used (in
      conjunction with Adler conditions) in order to form the porphyrin cap in situ.
      Additionally, the yields obtained via these conditions exhibited a significant
      improvement, relative to the traditional refluxing protocol hitherto reported.
      Capsules 20-25 are indefinitely stable, and we observed that 22 and 25 possess
      the smallest rigidified cavities yet reported for resorcin[4]arene cavitand
      capped porphyrin host molecules.

PMID- 19763300
TI  - Introduction of methyl groups on vinylene segments of phenylene vinylene systems:
      synthesis and properties.
AB  - A facile synthetic route towards phenylene vinylene systems with methyl
      substituents at the vinyl linkages is demonstrated through palladium catalyzed
      Heck coupling of 1,4-diisopropenylbenzene with aryl bromides. The coupling leads
      to a series of model compounds that feature, in some cases, direct access to a
      trans-configuration at the double bonds. The oxidative stability of these systems
      is surprisingly unaffected by the presence of allylic C-H bonds in the methyl
      substituents. The methyl substituents modulate the electronic properties of the
      phenylene vinylene systems by inducing a significant twist to the conjugated
      backbone. The study suggests that the introduction of methyl groups at vinylene
      sites is a viable alternative to functionalising and tuning the properties of
      phenylene vinylene systems.

PMID- 19763299
TI  - Fluorogenic affinity label for the facile, rapid imaging of proteins in live
      cells.
AB  - Haloalkane dehalogenase (HD) catalyzes the hydrolysis of haloalkanes via a
      covalent enzyme-substrate intermediate. Fusing a target protein to an HD variant
      that cannot hydrolyze the intermediate enables labeling of the target protein
      with a haloalkane in cellulo. The utility of extant probes is hampered, however,
      by background fluorescence as well as limited membrane permeability. Here, we
      report on the synthesis and use of a fluorogenic affinity label that, after
      unmasking by an intracellular esterase, labels an HD variant in cellulo. Labeling
      is rapid and specific, as expected from the reliance upon enzymic catalysts and
      the high membrane permeance of the probe both before and after unmasking. Most
      notably, even high concentrations of the fluorogenic affinity label cause minimal
      background fluorescence without a need to wash the cells. We envision that such
      fluorogenic affinity labels, which enlist catalysis by two cellular enzymes, will
      find utility in pulse-chase experiments, high-content screening, and numerous
      other protocols.

PMID- 19763301
TI  - Fragment-based development of triazole-substituted O-galactosyl aldoximes with
      fragment-induced affinity and selectivity for galectin-3.
AB  - A fragment-based development of 3C-triazol-1-yl-O-galactopyranosyl aldoximes led
      to the discovery of highly selective and high affinity (K(d) down to 11 microm)
      small monosaccharide based inhibitors of galectin-3. Galectin-7, 8 N-terminal
      CRD, and 9 N-terminal CRD bound the inhibitors only weakly. The galectin-3
      selectivity was hypothesized to stem from interaction of the aldoxime moiety with
      a site not present in the other galectins.

PMID- 19763302
TI  - Synthesis of cyanoformamides from primary amines and carbon dioxide under mild
      conditions. Synthesis of ceratinamine.
AB  - Treatment of primary amines with tetramethylphenylguanidine (PhTMG) and a
      cyanophosphonate at -10 degrees Celsius under an atmosphere of carbon dioxide
      provides cyanoformamides in very high to excellent yields. The reaction proceeds
      efficiently within a short time. By-products were not detected in most runs and
      epimerization was not found when optically pure alpha-aminoesters were used as
      substrates. As an example, the reaction was applied to the synthesis of the
      marine natural product ceratinamine.

PMID- 19763303
TI  - A new one-pot hydroformylation/Strecker synthesis as a versatile synthetic tool
      for polyfunctional compounds and functionalization of dendrimers.
AB  - A versatile and high yielding one-pot hydroformylation/Strecker synthesis is
      reported for the synthesis of various alpha-aminonitriles. This methodology
      allows functionalization of dendrimers (e.g. polyamines 4-7) and hyper branched
      polymers (e.g. polyallyl glycerol 12) to give corresponding dendritic structures
      with alpha-aminonitriles and/or amino acids in the outer shell in good to
      excellent yields.

PMID- 19763304
TI  - Hindered Bronsted bases as Lewis base catalysts.
AB  - KHMDS and KOtBu are well established as strong, hindered, non-nucleophilic
      Bronsted bases. However, in the present work these bases are applied as highly
      active Lewis base catalysts for the formal [2+2] cycloaddition of ketenes with
      aldehydes and imines.

PMID- 19763305
TI  - A colorimetric and fluorescent merocyanine-based probe for biological thiols.
AB  - A new "dual-mode" chromogenic and fluorescent turn-on probe (2) for the selective
      sensing of biological thiols is reported. In MeOH-H(2)O cosolvent at
      physiological pH 7.40 (MeOH-H(2)O = 3:7), biological thiols cleave the 2,4
      dinitrobenzenesulfonyl group to release the chromo- and fluorophore merocyanine
      (3).

PMID- 19763306
TI  - N-(Acetamido)thiourea based simple neutral hydrogen-bonding receptors for anions.
AB  - N-(Acetamido)-N'-phenylthioureas (4-6) were found to be efficient anion receptors
      with higher anion affinity than their N-benzamido-N'-phenylthiourea counterparts
      (1 and 2). The N'-phenylthiourea moiety in 4-6 was shown to be the chromophore
      with an absorption maximum at ca. 270 nm. It was found that, in the presence of
      anions, the absorption at ca. 270 nm of 4-6 (except 5f) in acetonitrile (MeCN)
      was blue shifted and enhanced while a red-shifted shoulder appeared at ca. 295
      nm, together with an isosbestic point at ca. 240 nm. The 1:1 anion binding
      constants of 4-6, for example at 10(6)-10(7) M(-1) order of magnitude for AcO(-)
      in MeCN, were found to be higher than those of 1 and 2, although the acidity of
      the thioureido -NH protons in 4-6 is lower than that in 1 and 2. (1)H NMR data
      indicates that the N-N single bond in 4-6 is twisted but less than that in 1 and
      2. A conformation change at the N-N single bond of 4-6 was suggested to occur
      upon anion binding which leads to a planar hydrogen-bonding network in the anion
      binding complex in which a charge transfer takes place with the N-acyl moiety
      being the electron acceptor. Variations in the CD signals of a proline derivative
      6 bearing a chiral center in the N-amido moiety provide direct evidence for this
      conformation change upon its binding with anions in MeCN. The amplified effect of
      substituent X at the N'-phenyl ring of 5 on the anion binding constant supports
      the conclusion of anion-binding switched charge transfer in the anion binding
      complex. (1)H NMR and absorption titrations for 5 indicated that the anion
      receptor interaction was of a hydrogen-bonding nature until the N'-phenyl
      substituent X is as electron-withdrawing as m-CF(3) (5e). With X being the more
      electron-withdrawing p-NO(2) (5f), deprotonation of the thioureido -NH occurs in
      the presence of anion. Results reported here confirm that N-amidothioureas
      derived from both N-aliphatic and N-aromatic amides can in general be a family of
      efficient hydrogen-bonding receptors, with the aliphatic N-amido derivatives
      being more efficient. This provides a wider structural diversity for designing
      thiourea-based functional molecules such as anion receptors and organocatalysts.
      Preliminary experiments confirm that 6 could catalyse efficiently the reduction
      of nitrostyrene in CH(2)Cl(2) and MeCN.

PMID- 19763307
TI  - Nucleoside triphosphate mimicry: a sugar triazolyl nucleoside as an ATP
      competitive inhibitor of B. anthracis pantothenate kinase.
AB  - The synthesis of a library of nucleoside triphosphate mimetics is described where
      the Mg(2+) chelated triphosphate sidechain is replaced by an uncharged methylene
      triazole linked monosaccharide sidechain. The compounds have been evaluated as
      inhibitors of Bacillus anthracis pantothenate kinase and a competitive inhibitor
      has been identified with a K(i) that is 3-fold lower than the K(m) value of ATP.

PMID- 19763308
TI  - Homophymines B-E and A1-E1, a family of bioactive cyclodepsipeptides from the
      sponge Homophymia sp.
AB  - Nine new cyclodepsipeptides, homophymines B-E (2-5) and A1-E1 (1a-5a), were
      isolated from the polar extracts of the sponge Homophymia sp. The new structures,
      featuring new polyketide-derived end groups, were determined by interpretation of
      NMR and MS data. The configurations of the new end groups was secured by the
      application of J-based configurational analysis. Homophymines displayed very
      potent antiproliferative activity (IC(50) in the nM range) against a panel of
      human cancer cell lines.

PMID- 19763309
TI  - Cucurbit[7]uril host-guest and pseudorotaxane complexes with alpha,omega
      bis(pyridinium)alkane dications.
AB  - The host molecule cucurbit[7]uril forms very stable host-guest complexes (1:1 and
      2:1) and [2]pseudorotaxanes with alpha,omega-bis(pyridinium)alkane dications in
      aqueous solution. With the dications containing pyridinium, 2- and 3-picolinium,
      and 4-dimethylaminopyridinium end groups and a hexyl chain, [2]pseudorotaxanes
      are formed with one equivalent of CB[7] positioned over the central chain. A
      second equivalent of CB[7] encapsulating one of the end groups results in the
      translocation of the first CB[7] to the other end group. For the dications with
      these end groups, the 2:1 host-guest complexes exhibit stability constants which
      are considerably smaller than the 1:1 values as the result of steric and
      electronic repulsions between the two CB[7] hosts.

PMID- 19763310
TI  - A divergent strategy to the withasomnines.
AB  - A concise synthesis of three members of the withasomnine family of natural
      products is reported. The synthesis features a regioselective sydnone
      alkynylboronate cycloaddition followed by Suzuki cross coupling and silyl group
      removal, and marks the first divergent approach to this family of pyrazole based
      natural products.

PMID- 19763311
TI  - Lewis acid/CpRu dual catalysis in the enantioselective decarboxylative allylation
      of ketone enolates.
AB  - The addition of a Lewis acidic metal triflate salt Mg(OTf)(2) as co-catalyst in
      the CpRu-catalyzed decarboxylative allylation of in situ-generated ketone
      enolates allows the reaction to proceed at lower temperature with higher regio-
      and enantioselectivity. Even so-far-unreactive substrates react.

PMID- 19763312
TI  - Oxidative carboxylation of arylaldehydes with water by a sulfoxylalkyl
      substituted N-heterocyclic carbene catalyst.
AB  - The N-Heterocyclic carbene-catalysed oxidative carboxylation of arylaldehydes
      with water successfully proceeded when a sulfoxylalkyl-substituted imidazolium
      salt was used as the catalyst. The reactions can be run in the absence of
      oxidant, and a variety of arylaldehydes having an electron-withdrawing group were
      converted to the corresponding carboxylic acids.

PMID- 19763313
TI  - An efficient cascade synthesis of various 2H-1,4-benzoxazin-3-(4H)-ones from o
      halophenols and 2-halo-amides catalyzed by CuI.
AB  - A novel and efficient one-pot cascade synthesis of 2H-1,4-benzoxazin-3-(4H)-ones
      has been developed through copper-catalyzed coupling of o-halophenols and 2-halo
      amides. Various 2H-1,4-benzoxazin-3-(4H)-ones with diversity at three
      substituents on their scaffold have been synthesized conveniently in good to
      excellent yields.

PMID- 19763314
TI  - Free radical reaction between 2-benzoyl-1,4-benzoquinones and 1,3-dicarbonyl
      compounds.
AB  - A manganese(III)-mediated reaction between 2-benzoyl-1,4-benzoquinones and 1,3
      dicarbonyl compounds that produces benzo[c]furan-4,7-diones and anthracene-1,4
      diones with high chemoselectivity is described. With ethyl butyrylacetate, by
      changing the solvent, benzo[c]furan-4,7-diones and anthracene-1,4-diones can be
      generated in high chemoselectivities. With ethyl benzoylacetate, N ,N-dimethyl
      acetoacetamide and 1,3-diones, benzo[c]furan-4,7-diones were produced effectively
      with high selectivity. With 2-alkyl-5-benzoyl-1,4-benzoquinones, the
      regioselectivity of this reaction was also studied and the corresponding
      benzo[c]furan-4,7-dione and anthracene-1,4-dione derivatives were obtained in
      high regioselectivity.

PMID- 19763315
TI  - FtmOx1, a non-heme Fe(II) and alpha-ketoglutarate-dependent dioxygenase,
      catalyses the endoperoxide formation of verruculogen in Aspergillus fumigatus.
AB  - Verruculogen is a tremorgenic mycotoxin and contains an endoperoxide bond. In
      this study, we describe the cloning, overexpression and purification of a non
      heme Fe(ii) and alpha-ketoglutarate-dependent dioxygenase FtmOx1 from Aspergillus
      fumigatus, which catalyses the conversion of fumitremorgin B to verruculogen by
      inserting an endoperoxide bond between two prenyl moieties. Incubation with
      (18)O(2)-enriched atmosphere demonstrated that both oxygen atoms of the
      endoperoxide bond are derived from one molecule of O(2). FtmOx1 is the first
      endoperoxide-forming non-heme Fe(ii) and alpha-ketoglutarate-dependent
      dioxygenase reported so far. A mechanism of FtmOx1-catalysed verruculogen
      formation is postulated and discussed.

PMID- 19763316
TI  - ITAM-derived phosphopeptide-containing dendrimers as multivalent ligands for Syk
      tandem SH2 domain.
AB  - Spleen tyrosine kinase (Syk) is activated when its tandem SH2 domain (tSH2) binds
      to a diphosphorylated ITAM motif of e.g. the FcepsilonRI receptor. In this
      divalent interaction each SH2 domain binds to a phosphotyrosine-containing
      tetrapeptide motif in ITAM. One of those tetrapeptide sequences was synthesized
      and conjugated to dendrimers via 'click' chemistry to create a series of
      functional phosphopeptide-containing dendrimers ranging from a monovalent to an
      octavalent dendrimer. The affinity of the functionalized dendrimers for Syk tSH2
      has been assayed in SPR competition experiments. Both the tetra- and octavalent
      dendrimer had an affinity in the high nanomolar range, which is approximately 100
      fold enhanced compared to the monovalent tetrapeptide, indicating a multivalency
      effect.

PMID- 19763317
TI  - Synthesis and structural investigation of N-acyl selenophosphoramides.
AB  - 2-Amino-2-seleno-5,5-dimethyl-1,3,2-dioxaphosphorinane reacts with acyl chlorides
      (4-chlorobenzoyl chloride or pivaloyl chloride) yielding the respective N-acyl
      selenophosphoramides. These derivatives do not isomerise to the related
      selenocarbonyl imides. X-ray study of N-(4-chlorobenzoyl)-2-amino-2-seleno-5,5
      dimethyl-1,3,2-dioxaphosphorinane indicates that the selenium atom is placed in
      the equatorial position. The next compound studied, N-pivaloyl-2-amino-2-seleno
      5,5-dimethyl-1,3,2-dioxaphosphorinane, crystallises with both axial/equatorial
      conformers present in the asymmetric unit. Finally, 2-amino-2-seleno-5,5-dimethyl
      1,3,2-dioxaphosphorinane is present in the solid state in the form with the
      selenium atom in the axial position. The results are presented together with X
      ray structures of previously synthesised and described cyclic O-acyl
      monoselenophosphates.

PMID- 19763318
TI  - Modes of inactivation of trichodiene synthase by a cyclopropane-containing
      farnesyldiphosphate analog.
AB  - We describe quantum chemical calculations on the rearrangement of carbocations
      derived from a cyclopropane-containing analog of farnesyl diphosphate (FPP).
      These calculations reveal significant differences between the energetics for
      rearrangement of this analog and FPP itself, suggesting that the behavior of this
      substrate analog likely does not mirror that of the natural substrate. In
      addition, our results point to new mechanisms by which this FPP analog
      inactivates trichodiene synthase.

PMID- 19763319
TI  - Tautomerism of guanidines studied by (15)N NMR: 2-hydrazono-3-phenylquinazolin
      4(3H)-ones and related compounds.
AB  - 2-Hydrazono-3-phenylquinazolin-4(3H)-ones 11a-i are shown by (15)N NMR to exist
      in DMSO solution predominantly as the imino tautomers B and not the amino
      tautomers A. 2-Hydrazino-benzimidazole derivative 12 and 2-hydrazino-4,6
      dimethylpyrimidine derivative 13 were found to exist predominantly as the amino
      tautomers.

PMID- 19763320
TI  - Organocatalyzed highly stereoselective Michael addition of ketones to alkylidene
      malonates and nitroolefins using chiral primary-secondary diamine catalysts based
      on bispidine.
AB  - Organocatalysts containing primary-secondary diamines based on bispidine have
      been developed to catalyze the asymmetric Michael addition of ketones to
      alkylidene malonates and nitroalkenes. The corresponding products were obtained
      in high yields (up to 99%) with high diastereoselectivities (up to 99:1) and high
      enantioselectivities (up to 97% ee) under mild conditions using either
      environmentally benign water as the solvent or no solvent.

PMID- 19763323
TI  - Theoretical models of spontaneous activity generation and propagation in the
      developing retina.
AB  - Spontaneous neural activity is present in many parts of the developing nervous
      system, including visual, auditory and motor areas. In the developing retina,
      nearby neurons are spontaneously active and produce propagating patterns of
      activity, known as retinal waves. Such activity is thought to instruct the
      refinement of retinal axons. In this article we review several computational
      models used to help evaluate the mechanisms that might be responsible for the
      generation of retinal waves. We then discuss the models relative to the molecular
      mechanisms underlying wave activity, including gap junctions, neurotransmitters
      and second messenger systems. We examine how well the models represent these
      mechanisms and propose areas for future modelling research. The retinal wave
      models are also discussed in relation to models of spontaneous activity in other
      areas of the developing nervous system.

PMID- 19763324
TI  - Explorations in topology-delving underneath the surface of genetic interaction
      maps.
AB  - High throughput assays, as well as advances in computational approaches, have
      recently allowed the acquisition of vast amounts of genetic interaction (GI) data
      in several organisms. Since GIs are a functional measure that reports on the
      effect of a mutation in one gene on the phenotype of a mutation in another, they
      can serve as a powerful tool to study both the function of individual genes and
      the wiring of biological networks. Therefore, these data hold much promise for
      advancing our understanding of cellular systems. In this review we focus on the
      methodologies currently available for using and interpreting large datasets of
      GIs for functional gene groups (GI maps), and elaborate on the challenges ahead.
      In addition, we discuss potential applications for the study of evolution and
      disease mechanisms, and highlight the need for comprehensive integrative analysis
      to extract the wealth of information found in these maps.

PMID- 19763325
TI  - Scoring overlapping and adjacent signals from genome-wide ChIP and DamID assays.
AB  - Much of the research utilising genome-wide ChIP and DamID assays aims to
      understand the combinatorial feature of transcription factor binding and the
      chromatin modification code. With these experimental methods becoming more
      affordable and widespread, the focus of research is shifting to making sense of
      the data. Amongst the many challenges arising from data analyses, we are
      concerned with identifying biologically meaningful co-occurrences of
      transcription factor binding or chromatin modifications, using genome-wide
      profiles generated from ChIP and DamID assays. Co-occurrences are reflected in
      overlapping and adjacent signals in multiple ChIP or DamID profiles. We review
      existing quantitative methods to score overlaps and to cluster binding events in
      ChIP and DamID profiles. For pairwise comparison, existing methods either are
      based on a single score at the genome level or take a genomic, region-specific
      view. To draw inference from many profiles simultaneously, methods exist to
      cluster regions by their regulatory importance or to infer cis-regulatory modules
      for a particular region. We provide a simple guide to some of the statistical
      tools used by these methods.

PMID- 19763326
TI  - Structural interactomics: informatics approaches to aid the interpretation of
      genetic variation and the development of novel therapeutics.
AB  - Here we review the use of informatics in structural interactomics, with
      particular emphasis on understanding interfacial contacts in the development of
      novel therapeutics and the interpretation of genetic variation. We describe the
      availability and applicability of structural databases of protein interactions
      which facilitate this endeavour. We demonstrate the applicability of a structural
      interactomics approach to the study of the fibroblast growth factor (FGF)
      stimulated mitogen-activated protein kinase (MAPK) pathway.

PMID- 19763327
TI  - Molecular modeling and docking studies of human 5-hydroxytryptamine 2A (5-HT2A)
      receptor for the identification of hotspots for ligand binding.
AB  - The serotonergic system has been implicated in emotional and cognitive function.
      In particular, 5-HT(2A) (5-hydroxytrytamine receptor 2A) is attributed to a
      number of disorders like schizophrenia, depression, eating disorders and anxiety.
      5-HT(2A), being a GPCR (G-protein coupled receptor), is important in the
      pharmaceutical industry as a proven target for these disorders. Despite their
      extensive clinical importance, the structural studies of this protein is lacking
      due to difficulties in determining its crystal structure. We have performed
      sequence analysis and molecular modeling of 5-HT(2A) that has revealed a set of
      conserved residues and motifs considered to play an important role in maintaining
      structural integrity and function of the receptor. The analysis also revealed a
      set of residues specific to the receptor which distinguishes them from other
      members of the subclass and their orthologs. Further, starting from the model
      structure of human 5-HT(2A) receptor, docking studies were attempted to envisage
      how it might interact with eight of its ligands (such as serotonin, dopamine,
      DOI, LSD, haloperidol, ketanserin, risperidone and clozapine). The binding
      studies of dopamine to 5-HT(2A) receptor can bring up better understanding in the
      etiology of a number of neurological disorders involving both these two
      receptors. Our sequence analysis and study of interactions of this receptor with
      other ligands reveal additional residue hotspots such as Asn 363 and Tyr 370. The
      function of these residues can be further analyzed by rational design of site
      directed mutagenesis. Two distinct binding sites are identified which could play
      important roles in ligand binding and signaling.

PMID- 19763328
TI  - Unraveling the potential of intrinsically disordered proteins as drug targets:
      application to Mycobacterium tuberculosis.
AB  - Many eukaryotic and prokaryotic proteins remain disordered under physiological
      conditions and often acquire a stable secondary structure on binding to their
      cellular targets. Though the process of binding is still under analysis, it has
      been found that the flexibility of proteins can add to their functionality. This
      motivated us to explore intrinsically disordered proteins (IDPs) as drug targets.
      In silico studies have been carried out on Mycobacterium tuberculosis, which,
      with emergence of hyper-virulent and drug resistant strains, XDRs and MDRs, is
      one of the most dreaded pathogens in the modern world. Our study reports 13 IDPs
      as potential drug targets, and three of them--FtsW (Rv2154c), GlmU (Rv1018c) and
      Obg (Rv2440c)--are chosen as key proteins and are described in detail. Future
      applications of this method can provide new insight into understanding the
      molecular mechanism of IDPs and their potential role as drug targets.

PMID- 19763329
TI  - Prediction of conditional gene essentiality through graph theoretical analysis of
      genome-wide functional linkages.
AB  - The genome of an organism characterizes the complete set of genes that it is
      capable of encoding. However, not all of the genes are transcribed and translated
      under any defined condition. The robustness that an organism exhibits to
      environmental perturbations is partly conferred by the genes that are
      constitutively expressed under all the conditions, and partly by a subset of
      genes that are induced under the defined conditions. The conditional importance
      of genes in conferring robustness can be understood in the context of the
      functional attributes of these genes and their correlations to the defined
      environmental conditions. However, a priori prediction of such genes for a given
      condition is yet not possible. We have attempted such predictions by integrating
      the available gene expression data with genome-wide functional linkages through
      the well known centrality-lethality correlations in graph theory. We make use of
      three distinct concepts of centrality, namely, degree, closeness and betweenness,
      which yield mutually complementary information. We then demonstrate the efficacy
      of combined graph theoretical and machine learning approaches in ranking
      essential nodes from a large network of genome-wide functional linkages, which
      yields predictions with high accuracy. We therefore perceive such predictions as
      highly useful in applications such as defining and prioritizing drug targets.

PMID- 19763330
TI  - On the basic computational structure of gene regulatory networks.
AB  - Gene regulatory networks constitute the first layer of the cellular computation
      for cell adaptation and surveillance. In these webs, a set of causal relations is
      built up from thousands of interactions between transcription factors and their
      target genes. The large size of these webs and their entangled nature make it
      difficult to achieve a global view of their internal organisation. Here, this
      problem has been addressed through a comparative study of Escherichia coli,
      Bacillus subtilis and Saccharomyces cerevisiae gene regulatory networks. We
      extract the minimal core of causal relations, uncovering the hierarchical and
      modular organisation from a novel dynamical/causal perspective. Our results
      reveal a marked top-down hierarchy containing several small dynamical modules for
      E. coli and B. subtilis. Conversely, the yeast network displays a single but
      large dynamical module in the middle of a bow-tie structure. We found that these
      dynamical modules capture the relevant wiring among both common and organism
      specific biological functions such as transcription initiation, metabolic
      control, signal transduction, response to stress, sporulation and cell cycle.
      Functional and topological results suggest that two fundamentally different forms
      of logic organisation may have evolved in bacteria and yeast.

PMID- 19763331
TI  - A global view of Escherichia coli Rsd protein and its interactions.
AB  - The Escherichia coli Rsd protein forms 1 : 1 complexes with sigma(70) protein,
      which is the major factor in determining promoter recognition by RNA polymerase.
      Here we describe measurements of the levels of Rsd, RNA polymerase, sigma(70) and
      the alternative sigma(38) factor. Rsd levels are sufficient to sequester a
      significant proportion of sigma(70) and immunoaffinity pull-down experiments show
      that this occurs in stationary phase but not in exponentially growing cells. Rsd
      expression is controlled by two promoters, P1 and P2. Experiments with lac
      fusions show that the P2 promoter is stronger than P1, that P2 is active in all
      phases of growth, and that this accounts for the high levels of Rsd.

PMID- 19763332
TI  - Ligand dependent intra and inter subunit communication in human tryptophanyl tRNA
      synthetase as deduced from the dynamics of structure networks.
AB  - Homodimeric protein tryptophanyl tRNA synthetase (TrpRS) has a Rossmann fold
      domain and belongs to the 1c subclass of aminoacyl tRNA synthetases. This enzyme
      performs the function of acylating the cognate tRNA. This process involves a
      number of molecules (2 protein subunits, 2 tRNAs and 2 activated Trps) and thus
      it is difficult to follow the complex steps in this process. Structures of human
      TrpRS complexed with certain ligands are available. Based on structural and
      biochemical data, mechanism of activation of Trp has been speculated. However, no
      structure has yet been solved in the presence of both the tRNA(Trp) and the
      activated Trp (TrpAMP). In this study, we have modeled the structure of human
      TrpRS bound to the activated ligand and the cognate tRNA. In addition, we have
      performed molecular dynamics (MD) simulations on these models as well as other
      complexes to capture the dynamical process of ligand induced conformational
      changes. We have analyzed both the local and global changes in the protein
      conformation from the protein structure network (PSN) of MD snapshots, by a
      method which was recently developed in our laboratory in the context of the
      functionally monomeric protein, methionyl tRNA synthetase. From these
      investigations, we obtain important information such as the ligand induced
      correlation between different residues of this protein, asymmetric binding of the
      ligands to the two subunits of the protein as seen in the crystal structure
      analysis, and the path of communication between the anticodon region and the
      aminoacylation site. Here we are able to elucidate the role of dimer interface at
      a level of detail, which has not been captured so far.

PMID- 19763333
TI  - DNA supercoiling regulates the stress-inducible expression of genes in the
      cyanobacterium Synechocystis.
AB  - Changes in the supercoiling of genomic DNA play an important role in the
      regulation of gene expression. We compared the genome-wide expression of genes in
      cells of the cyanobacterium Synechocystis sp. PCC 6803 when they were subjected
      to salt, cold, and heat stress, in the presence of novobiocin, an inhibitor of
      DNA gyrase, and in its absence. The analysis revealed that the expression of a
      large number of stress-inducible genes depends on the extent of genomic DNA
      supercoiling. The function of the two-component regulatory systems, which are
      known as sensors and transducers of salt, cold, and heat stress, depends on, and
      might be controlled by, the degree of supercoiling of the genomic DNA. These
      results suggest that stress-induced changes in superhelicity of genomic DNA
      provide an important permissive background for successful acclimatization of
      cyanobacterial cells to stress conditions.

PMID- 19763334
TI  - From genes to cells to tissues--modelling the haematopoietic system.
AB  - Haematopoiesis (or blood formation) in general and haematopoietic stem cells more
      specifically represent some of the best studied mammalian developmental systems.
      Sophisticated purification protocols coupled with powerful biological assays
      permit functional analysis of highly purified cell populations both in vitro and
      in vivo. However, despite several decades of intensive research, the sheer
      complexity of the haematopoietic system means that many important questions
      remain unanswered or even unanswerable with current experimental tools.
      Scientists have therefore increasingly turned to modelling to tackle complexity
      at multiple levels ranging from networks of genes to the behaviour of cells and
      tissues. Early modelling attempts of gene regulatory networks have focused on
      core regulatory circuits but have more recently been extended to genome-wide
      datasets such as expression profiling and ChIP-sequencing data. Modelling of
      haematopoietic cells and tissues has provided insight into the importance of
      phenotypic heterogeneity for the differentiation of normal progenitor cells as
      well as a greater understanding of treatment response for particular pathologies
      such as chronic myeloid leukaemia. Here we will review recent progress in
      attempts to reconstruct segments of the haematopoietic system. A variety of
      modelling strategies will be covered from small-scale, protein-DNA or protein
      protein interactions to large scale reconstructions. Also discussed will be
      examples of how stochastic modelling may be applied to multi cell systems such as
      those seen in normal and malignant haematopoiesis.

PMID- 19763335
TI  - An integrative approach towards completing genome-scale metabolic networks.
AB  - Genome-scale metabolic networks which have been automatically derived through
      sequence comparison techniques are necessarily incomplete. We propose a strategy
      that incorporates genomic sequence data and metabolite profiles into modeling
      approaches to arrive at improved gene annotations and more complete genome-scale
      metabolic networks. The core of our strategy is an algorithm that computes
      minimal sets of reactions by which a draft network has to be extended in order to
      be consistent with experimental observations. A particular strength of our
      approach is that alternative possibilities are suggested and thus experimentally
      testable hypotheses are produced. We carefully evaluate our strategy on the well
      studied metabolic network of Escherichia coli, demonstrating how the predictions
      can be improved by incorporating sequence data. Subsequently, we apply our method
      to the recently sequenced green alga Chlamydomonas reinhardtii. We suggest
      specific genes in the genome of Chlamydomonas which are the strongest candidates
      for coding the responsible enzymes.

PMID- 19763336
TI  - Correlation between mRNA expression levels and protein aggregation propensities
      in subcellular localisations.
AB  - We investigate the relationship between mRNA expression levels and protein
      aggregation propensities at the proteomic level, and find that these quantities
      exhibit a significant correlation when they are averaged across subcellular
      localisations. In order to investigate this phenomenon, we study the dependence
      of mRNA expression levels and protein aggregation propensities on the volume of
      the corresponding subcellular localisations, finding that proteins tend to be
      increasingly more abundant and more soluble with decreasing volumes of their
      subcellular localisations. These results indicate that the maintenance of protein
      solubility plays an even greater role than previously thought in sustaining
      protein homeostasis.

PMID- 19763337
TI  - Modular logical modelling of the budding yeast cell cycle.
AB  - Systems biologists are facing the difficult challenge of modelling and analysing
      regulatory networks encompassing numerous and diverse components and
      interactions. Furthermore, available data sets are often qualitative, which
      complicates the definition of truly quantitative models. In order to build
      comprehensive and predictive models, there is clearly a need for incremental
      strategies, enabling the progression from relatively small to large scale models.
      Leaning on former models, we have defined a logical model for three regulatory
      modules involved in the control of the mitotic cell cycle in budding yeast,
      namely the core cell cycle module, the morphogenetic checkpoint, and a module
      controlling the exit from mitosis. Consistency with available data has been
      assessed through a systematic analysis of model behaviours for various genetic
      backgrounds and other perturbations. Next, we take advantage of compositional
      facilities of the logical formalism to combine these three models in order to
      generate a single comprehensive model involving over thirty regulatory
      components. The resulting logical model preserves all relevant characteristics of
      the original modules, while enabling the simulation of more sophisticated
      experiments.

PMID- 19763338
TI  - A c-Myc regulatory subnetwork from human transposable element sequences.
AB  - Transposable elements (TEs) can donate regulatory sequences that help to control
      the expression of human genes. The oncogene c-Myc is a promiscuous transcription
      factor that is thought to regulate the expression of hundreds of genes. We
      evaluated the contribution of TEs to the c-Myc regulatory network by searching
      for c-Myc binding sites derived from TEs and by analyzing the expression and
      function of target genes with nearby TE-derived c-Myc binding sites. There are
      thousands of TE sequences in the human genome that are bound by c-Myc. A
      conservative analysis indicated that 816-4564 of these TEs contain canonical c
      Myc binding site motifs. c-Myc binding sites are over-represented among sequences
      derived from the ancient TE families L2 and MIR, consistent with their
      preservation by purifying selection. Genes associated with TE-derived c-Myc
      binding sites are co-expressed with each other and with c-Myc. A number of these
      putative TE-derived c-Myc target genes are differentially expressed between
      Burkitt's lymphoma cells versus normal B cells and encode proteins with cancer
      related functions. Despite several lines of evidence pointing to their regulation
      by c-Myc and relevance to cancer, the set of genes identified as TE-derived c-Myc
      targets does not significantly overlap with two previously characterized c-Myc
      target gene sets. These data point to a substantial contribution of TEs to the
      regulation of human genes by c-Myc. Genes that are regulated by TE-derived c-Myc
      binding sites appear to form a distinct c-Myc regulatory subnetwork.

PMID- 19763339
TI  - Structure and organization of drug-target networks: insights from genomic
      approaches for drug discovery.
AB  - Recent years have seen an explosion in the amount of "omics" data and the
      integration of several disciplines, which has influenced all areas of life
      sciences including that of drug discovery. Several lines of evidence now suggest
      that the traditional notion of "one drug-one protein" for one disease does not
      hold any more and that treatment for most complex diseases can best be attempted
      using polypharmacological approaches. In this review, we formalize the definition
      of a drug-target network by decomposing it into drug, target and disease spaces
      and provide an overview of our understanding in recent years about its structure
      and organizational principles. We discuss advances made in developing promiscuous
      drugs following the paradigm of polypharmacology and reveal their advantages over
      traditional drugs for targeting diseases such as cancer. We suggest that drug
      target networks can be decomposed to be studied at a variety of levels and argue
      that such network-based approaches have important implications in understanding
      disease phenotypes and in accelerating drug discovery. We also discuss the
      potential and scope network pharmacology promises in harnessing the vast amount
      of data from high-throughput approaches for therapeutic advantage.

PMID- 19763340
TI  - Transcription regulatory networks in Caenorhabditis elegans inferred through
      reverse-engineering of gene expression profiles constitute biological hypotheses
      for metazoan development.
AB  - Differential gene expression governs the development, function and pathology of
      multicellular organisms. Transcription regulatory networks study differential
      gene expression at a systems level by mapping the interactions between regulatory
      proteins and target genes. While microarray transcription profiles are the most
      abundant data for gene expression, it remains challenging to correctly infer the
      underlying transcription regulatory networks. The reverse-engineering algorithm
      LeMoNe (learning module networks) uses gene expression profiles to extract
      ensemble transcription regulatory networks of coexpression modules and their
      prioritized regulators. Here we apply LeMoNe to a compendium of microarray
      studies of the worm Caenorhabditis elegans. We obtain 248 modules with a
      regulation program for 5020 genes and 426 regulators and a total of 24 012
      predicted transcription regulatory interactions. Through GO enrichment analysis,
      comparison with the gene-gene association network WormNet and integration of
      other biological data, we show that LeMoNe identifies functionally coherent
      coexpression modules and prioritizes regulators that relate to similar biological
      processes as the module genes. Furthermore, we can predict new functional
      relationships for uncharacterized genes and regulators. Based on modules involved
      in molting, meiosis and oogenesis, ciliated sensory neurons and mitochondrial
      metabolism, we illustrate the value of LeMoNe as a biological hypothesis
      generator for differential gene expression in greater detail. In conclusion,
      through reverse-engineering of C. elegans expression data, we obtained
      transcription regulatory networks that can provide further insight into metazoan
      development.

PMID- 19763341
TI  - Logical modelling of cell cycle control in eukaryotes: a comparative study.
AB  - Dynamical modelling is at the core of the systems biology paradigm. However, the
      development of comprehensive quantitative models is complicated by the daunting
      complexity of regulatory networks controlling crucial biological processes such
      as cell division, the paucity of currently available quantitative data, as well
      as the limited reproducibility of large-scale experiments. In this context,
      qualitative modelling approaches offer a useful alternative or complementary
      framework to build and analyse simplified, but still rigorous dynamical models.
      This point is illustrated here by analysing recent logical models of the
      molecular network controlling mitosis in different organisms, from yeasts to
      mammals. After a short introduction covering cell cycle and logical modelling, we
      compare the assumptions and properties underlying these different models. Next,
      leaning on their transposition into a common logical framework, we compare their
      functional structure in terms of regulatory circuits. Finally, we discuss assets
      and prospects of qualitative approaches for the modelling of the cell cycle.

PMID- 19763342
TI  - Systems analyses of circadian networks.
AB  - The circadian clock is a 24 hour timing device that co-ordinates biological
      activity with day/night cycles. The long history of systems analysis of circadian
      biology extends back to the first half of the last century when theoretical
      studies based on physiological experiments predicted the essential network
      properties, architecture and performance of circadian oscillators long before the
      first genetic components were isolated in the second half of the century. Systems
      approaches have continued to be important in analysing the circadian network in
      the model plant Arabidopsis thaliana and in mammals. We describe how systems
      analyses of transcriptional changes have led to formal mathematical models of
      circadian oscillators. Predictions within these mathematical models have been
      used to identify potential new components of circadian systems. Cross-referencing
      circadian regulation of transcript abundance with transcriptomic responses to
      abiotic and biotic signals has increased understanding of the nature of circadian
      clocks and their significance in regulating the daily life of plants and animals.
      We also highlight the need for systems analyses of the circadian regulation of
      proteins, metabolites and other physiological activities such as ion channel
      regulation.

PMID- 19763343
TI  - Systems-level approaches for identifying and analyzing genetic interaction
      networks in Escherichia coli and extensions to other prokaryotes.
AB  - Molecular interactions define the functional organization of the cell. Epistatic
      (genetic, or gene-gene) interactions, one of the most informative and commonly
      encountered forms of functional relationships, are increasingly being used to map
      process architecture in model eukaryotic organisms. In particular, 'systems
      level' screens in yeast and worm aimed at elucidating genetic interaction
      networks have led to the generation of models describing the global modular
      organization of gene products and protein complexes within a cell. However,
      comparable data for prokaryotic organisms have not been available. Given its ease
      of growth and genetic manipulation, the Gram-negative bacterium Escherichia coli
      appears to be an ideal model system for performing comprehensive genome-scale
      examinations of genetic redundancy in bacteria. In this review, we highlight
      emerging experimental and computational techniques that have been developed
      recently to examine functional relationships and redundancy in E. coli at a
      systems-level, and their potential application to prokaryotes in general.
      Additionally, we have scanned PubMed abstracts and full-text published articles
      to manually curate a list of approximately 200 previously reported synthetic sick
      or lethal genetic interactions in E. coli derived from small-scale experimental
      studies.

PMID- 19763344
TI  - Scaling relationship in the gene content of transcriptional machinery in
      bacteria.
AB  - The metabolic, defensive, communicative and pathogenic capabilities of eubacteria
      depend on their repertoire of genes and ability to regulate the expression of
      them. Sigma and transcription factors have fundamental roles in controlling these
      processes. Here, we show that sigma, transcription factors (TFs) and the number
      of protein coding genes occur in different magnitudes across 291 non-redundant
      eubacterial genomes. We suggest that these differences can be explained based on
      the fact that the universe of TFs, in contrast to sigma factors, exhibits a
      greater flexibility for transcriptional regulation, due to their ability to sense
      diverse stimuli through a variety of ligand-binding domains by discriminating
      over longer regions on DNA, through their diverse DNA-binding domains, and by
      their combinatorial role with other sigmas and TFs. We also note that the
      diversity of extra-cytoplasmic sigma factors and TF families is constrained in
      larger genomes. Our results indicate that most widely distributed families across
      eubacteria are small in size, while large families are relatively limited in
      their distribution across genomes. Clustering of the distribution of
      transcription and sigma families across genomes suggests that functional
      constraints could force their co-evolution, as was observed in sigma54, IHF and
      EBP families. Our results also indicate that large families might be a
      consequence of lifestyle, as pathogens and free-living organisms were found to
      exhibit a major proportion of these expanded families. Our results suggest that
      understanding proteomes from an integrated perspective, as presented in this
      study, can be a general framework for uncovering the relationships between
      different classes of proteins.

PMID- 19763345
TI  - Surgery--a challenge in haemophiliacs with inhibitors.
AB  - Treatment of haemophiliacs with inhibitors is of great concern in low-income
      countries confronting shortage in substitutive treatment. Invasive interventions
      on these patients represent a major challenge due to the fact that costs are
      significantly higher in comparison to similar procedures conducted on patients
      without inhibitors. OBJECTIVE: In the context of insufficient availability of
      clotting factor, we aimed at highlighting the experience of surgical treatment in
      inhibitor patients. We analyzed the indications, types of performed interventions
      and outcomes. PATIENTS, METHODS: This single center, retrospective analysis has
      been conducted on 7 inhibitor patients registered and treated in Haemophilia
      Center of Timisoara over ten years (1997-2007): six patients with severe
      hemophilia A (3 - high titer, 3 - low titer), one patient with von Willebrand
      disease (low titer).Three patients developed inhibitors only after 2-5 days post
      surgery. RESULTS: A total of 15 invasive procedures were carried out: 2
      orthopedic interventions (1 arthrodesis, 1 arthroscopic synovectomy), 2
      urogenital interventions (1 surgical testicular detorsion, 1 orchiectomy), 4 limb
      amputations (2 bilateral upper and 2 lower limb amputation), 2 pseudotumour (PT)
      surgery interventions, 5 drainages (2 massive pyohaemothorax, 1 drainage of shank
      haematoma, 1 drainage of compressive forearm haematoma, 1 drainage of thigh
      haematoma). Haemostasis was achieved in patients with low level inhibitors (< 5
      BU/ml) with high doses of FVIII concentrates; in those with high inhibitor level
      (> 5 BU/ml), surgery was managed using by-passing agents. Supplementation with
      local fibrin glue and intravenous or local antifibrinolytic agents was given in
      68.75% of interventions. Postoperative complications consisted of haemorrhagic
      shock in 13.33% of interventions and infection in 6.66%. Haemostatic outcome was
      evaluated by blood loss and duration of treatment, compared to expectations for
      non-inhibitor patients. The outcome was excellent and good in 66.66% of
      interventions, and fair in 33.33%. Discussion, conclusion: Indication of invasive
      procedures in haemophiliacs with inhibitors was limited to life and/or limb
      threatening situations. In low-income countries, inhibitor and recovery of FVIII
      monitoring is mandatory in the postoperative follow-up of patients with low or no
      substitution prior to surgery due to false negative results at the preoperative
      investigation.

PMID- 19763346
TI  - Malignant stroke in an adolescent with a homozygous MTHFR 677CT mutation and
      intake of hormonal contraceptives.
AB  - Severe stroke in children and adolescents with its devastating long term
      consequences remains a rare disorder with many open questions. Beside the well
      known risk factors such as infection or congenital and acquired heart disease,
      coagulation disorders have to be considered in the differential work up of the
      underlying aetiology. Here we report the case of an adolescent with a homozygote
      MTHFR 677CT mutation suffering a malignant stroke shortly after the start of oral
      contraceptives. CONCLUSION: Since prevention seems easily feasible, general
      screening for MTHFR mutations might be worthwhile in women before starting oral
      contraceptives.

PMID- 19763347
TI  - [DHR--ready for take-off].
AB  - The collaboration between the Paul-Ehrlich-Institute (PEI) and the GTH as well as
      the two patient organisations, DHG and IGH has been official since February 2007
      with the signing of the collaboration contract. In December 2008, the University
      of Munich started data enrollment. The DHR is a new software development which
      includes matters and modules of epidemiological as well as clinical cancer
      registries. Instead of collaborating with a trustee for personal data the DHR is
      using a so called "Intermediate". Intermediate is an independent software module
      installed on a separate server without hard disk and with solely random access
      memory. It receives personal data from the treaters over the internet, calculates
      the pseudonyms, which are then forwarded to the database. The Intermediate needs
      to be protected from data access by the PEI and its operating system and software
      has to be started afresh with each start. These facts require the involvement of
      a trustworthy third party. It shuts Intermediate off from the PEI without itself
      coming into the possession of personal data.

PMID- 19763348
TI  - [Haemophilia and knee function: are there differences between haemophilic and
      healthy children?].
AB  - With early prophylactic treatment our haemophilic children grow up in good
      health. Nevertheless, we cannot prevent every bleeding. Those bleedings may be
      just subclinical but they could lead to overloading of the knee and more and more
      of the ankle joint in the long term. Motion analysis can help to understand this
      process and prevent it. A comparison of the gait function of haemophilic and
      healthy children of the age 3-18 years showed distinct functional differences
      especially in the youngest age group (3-6 years). Apparently, the coordination
      skill gait rhythm was significantly worse in the heamophilic group. All measured
      functional deficits can be treated with physiotherapy. Possible reasons for these
      early functional differences are overprotection and/or early subclinical
      bleedings.

PMID- 19763349
TI  - [Out-patients haemophilia treatment in hospital: status quo of the legal basis
      for care-agreements].
AB  - Although hospitals primarily provide treatment for in-patients, treatment is also
      given to a large number of out-patients. The law covering haemophilia patients,
      who receive their treatment as out-patients, actually has several different
      bases. This has advantages and disadvantages. The question concerning us: Which,
      at the moment, is the best legal basis for any care-agreement? Another important
      factor for any agreement between the two parties, is that there should be a broad
      consensus, based on shared interests. The common aim should be the future
      guarantee for the treatment of patients suffering from haemophilia in suitable
      medical facilities. At the same time care must be taken to provide an efficient
      and economically viable care-service for these patients, as well as ensuring that
      the quality and efficiency of the service remain transparent.

PMID- 19763350
TI  - [Upper ankle joint prostheses in haemophilia patients].
AB  - Secondary arthrosis of the upper ankle joint (talocalcanean joint) is one of the
      most frequent forms of haemophilic arthropathy. It is a secondary form of
      arthrosis not only because of chronic synovitis and cartilage injury resulting
      from chronic recurrent intraarticular bleeds, but also due to the misalignment of
      the joint and abnormal joint stress. The consequences are manifest even in young
      patients and finally lead to subtalar joint ankylosis with the biomechanical
      disorder of foot drop (talipes equinus). In such clinical situations,
      implantation of a subtalar joint endoprosthesis is a viable alternative to
      arthrodesis. CASE REPORT: A man (age: 52 years), suffering from severe
      haemophilia A (residual FVIII activity < 1 %), no inhibitor formation. The
      patient has a history of several years of painful ankylosis of the right ankle
      joint and minor talipes equinus, and suffers from symptomatic talonavicular
      arthrosis. Open joint cleansing considerably improved mobility in the upper ankle
      joint and alleviated the pain in the talonavicular joint. However, the recovered
      mobility of the arthrotic upper ankle joint also activated the patient's
      arthrosis, associated with severe pain. As there was no contraindication to upper
      ankle joint replacement, a cement-free prosthesis was implanted. Three months
      after surgery, the patient was mobile, with good foot rolling properties without
      orthopedic aids, and without pain in his upper joint ankle. CONCLUSION: In terms
      of biomechanics an upper ankle joint endoprosthesis is a superior alternative to
      arthrodesis in haemophilia patients. In order to minimize the complication rate,
      the treatment of haemophilia patients should be restricted to specially equipped
      interdisciplinary treatment centers with adequately trained and experienced
      surgeons as well as haemostaseologists.

PMID- 19763351
TI  - [Pseudo tumours in haemophilia patients].
AB  - Pseudo tumours are amongst the rare yet pathognomonic complications of
      haemophilia. They are old, encapsulated haematomas which due to their sometimes
      enormous size can cause massive complaints. These haematomas are surrounded by a
      thick fibrous capsule. They are attributed to persistent bleedings. The
      pathophysiology of pseudo tumors is not conclusively established yet. Some
      believe that they originate from bone material or the periosteum, while others
      suggest their development from soft tissue. They spread aggressively, displace
      the surrounding tissue, and cause secondary periosteal erosion of the bone. This
      results in bone resorption and destruction of surrounding muscular and soft
      tissue. Pseudo tumours develop slowly over many years. They occur primarily in
      adults and are largely unresponsive to conservative treatment. CASE: A 48-year
      old man with moderate hemophiliaA (FVIII:C 2%) and no FVIII inhibitor. Due to
      recurrent bleeding into the muscle of the right thigh diagnosis of two pseudo
      tumours (psoas, adductor magnus). In 2004 tumour extirpation with subsequent
      relapse; because of high local bleeding tendency (despite permanent prophylaxis
      with FVIII concentrate and adjusted lifestyle) surgical revision in 02/2008.
      Postoperatively, no recurrent bleeding; the patient is fully fit for work three
      months later. CONCLUSION: In order to reduce the complication rate when a pseudo
      tumor is suspected, patients should be treated in a specially equipped
      interdisciplinary center with adequately trained and experienced surgeons and
      haemostaseologists.

PMID- 19763352
TI  - [Desmopressin testing in children with von Willebrand syndrome in
      haemostaseologic centers of Saxonia, Saxonia-Anhalt and Thuringia].
AB  - The influence of desmopressin on hemostasis is mediated by the release of von
      Willebrand factor and of coagulation factor VIII from vascular endothelium. The
      necessity of testing desmopressin effectiveness on hemostasis is a matter of
      controversy and the performance of the test is not yet standardized. For this
      reason the desmopressin tests in 114 children with von Willebrand syndrome (type
      1, n=98; type 2A, n=12; type 2M, n=2; type 2N, n=2) carried out in 7 paediatric
      haemostaseologic centers were retrospectively analyzed. The effectiveness of
      desmopressin was assessed using defined response criteria. As expected, the test
      performance showed a wide variation among the centers. In 99 children
      desmopressin was given intravenously as a short infusion at a dosage ranging from
      0.25 to 0.41 microg/kg and in 15 intranasally at an absolute dose of 40 to 300
      microg. The points of time for blood taking after desmopressin application ranged
      from 0.5 to 12 h. The absent desmopressin response in 7 patients (6%) and the
      partial response in 15 indicate the necessity of testing desmopressin
      effectiveness before the first therapeutic use. The application of desmopressin
      was well tolerated by the patients.

PMID- 19763353
TI  - [Austrian haemophilia registry: up-date 2008 ].
AB  - The treatment of haemophilia requires continuous development of knowledge related
      to various aspects of diagnosis and therapy. It is, therefore, essential to
      collect valid and representative data, which are comparable on an international
      level. The Austrian Haemophilia Registry was set up by the Scientific Advisory
      Panel of the Austrian Haemophilia Society and by the patient organisation. For
      the design, it was decided to divide the registry into three sections, two
      concerning quality control and a third concerning scientific questions, the
      latter requiring written informed consent. A web-based software is used to
      collect data. Transfer and storage of data are secured and the server is situated
      in a computer center with video and access control. Data entry was initiated
      early 2008. Currently, only preliminary data are available. Our further focus is
      on continued data entry, which will further enable us to provide information
      concerning the characteristics of the haemophilia patient population in Austria
      and the actual treatment modalities used.

PMID- 19763354
TI  - [Morbidity and mortality of patients with haemophilia in Germany 2007/2008].
AB  - Since 1978 an annual multicentric survey regarding the epidemiology of patients
      suffering of haemophilia is performed with support of haemophilia treating
      centres of any size. Again the actual compilation is resting upon a broad
      database returning to over 30 years of inquiry well representing both the actual
      and retrospective status of mortality. Prompted was exclusively information about
      patients with haemophilia A, B and von Willebrand disease. In particular
      anonymous data concerning the last 12 months about number of treated patients,
      type and severity of illness, HIV-status and detailed information about causes of
      death was inquired. This data was merged with existing data and analyzed
      statistically. In the 2007/2008 survey, a total number of 8904 patients with
      bleeding disorders have been reported from 63 participating centres. Despite
      mortality from HIV in patients with haemophilia is keeping on decreasing, HIV
      still remains an important factor as an HIV/HCV coinfection seems to increase
      risk of progression of severe liver disease. Age structure in our patients has
      been shifting significantly over the last decades bringing age distribution into
      line with the entire population. This has to be considered assessing mortality
      and morbidity.

PMID- 19763355
TI  - Treatment of haemophilia in the elderly.
AB  - Treatment of elderly patients with haemophilia is an upcoming challenge in
      haemophilia care. We included patients with haemophilia A older than 60 years of
      age, who visited our haemophilia centre between 2006 and 2008. We conducted a
      retrospective study focussing on the patients' co-morbidities as well as changes
      in their bleeding patterns between 2003 and 2008. RESULTS: There is a tendency of
      increasing bleeding symptoms with increasing age of the patients due to more
      frequent spontaneous joint bleedings, malignancies or treatment with
      phenprocoumon or ASS. In consequence, FVIII dosage had to be increased for 8
      patients (28%). Chronic hepatitis C, coronary heart disease and malignancies are
      the most frequent co-morbidities.

PMID- 19763356
TI  - Development of a plasma- and albumin-free recombinant von Willebrand factor.
AB  - Baxter has developed a recombinant therapy for treating von Willebrand's disease.
      Recombinant VWF is co-expressed with the rFVIII in CHO cells used to produce the
      rFVIII product Advate. This rVWF is used as a drug component for a rVWF-rFVIII
      complex drug product. CHO cells produce partially processed and partially un
      processed rVWF still containing the pro-peptide. In order to make a consistent
      preparation containing mature and processed rVWF only rVWF is exposed to
      recombinant furin to remove the pro-peptide. Recombinant VWF and furin are
      produced under serum- and protein-free conditions. It is highly purified by a
      series of chromatographic steps and formulated in a protein-free buffer and has a
      homogeneous multimer distribution. The specific activity is higher in rVWF than
      in commercial plasma-derived VWF-FVIII complex products. SDS agarose
      electrophoretic analysis shows the presence of ultra-high molecular weight
      multimers. The FVIII-binding capacity and affinity of rVWF to FVIII is comparable
      to VWF in plasma. Carbohydrate analysis shows an intact glycosylation pattern.
      Recombinant VWF binds to collagen and promotes platelet adhesion under shear
      stress. It stabilizes endogenous FVIII in VWF-deficient knock-out mice as seen by
      a secondary rise in murine FVIII.

PMID- 19763357
TI  - Radiosynoviorthesis in children with haemophilia.
AB  - Recurrent bleeding into joints represents the clinical hallmark of haemophilia
      and, if not adequately treated, it may cause chronic synovitis and degenerative
      arthropathy. The first treatment option of recurrent haemarthroses and/or chronic
      synovitis is represented by synoviorthesis, both chemical and radioisotopic, with
      a success rate of approximately 80% for both. However, radioisotopic
      synoviorthesis should be preferred because it makes it possible to obtain
      complete synovial fibrosis usually in one session, without the need for repeated
      injections, thus reducing the risk of bleeding complications and concentrate
      consumption. For all these reasons this procedure should be implemented and
      supported, particularly in developing countries.

PMID- 19763358
TI  - Calibrated automated thrombin generation in paediatric patients with inflammatory
      bowel disease.
AB  - In adults, inflammatory bowel disease (IBD) is associated with an increased risk
      of thromboembolic complications. The pathogenesis of IBD is not really clear and
      a high thrombin activity might contribute to disease progression. We wanted to
      see whether children with IBD have a higher thrombin generation (TG). PATIENTS,
      MATERIAL, METHODS: Plasma samples were collected of 20 patients with IBD and of
      60 healthy controls (age range from 10 to 19). TG was measured by means of
      Calibrated automated thrombography (CAT). The disease activity was estimated,
      using the Pediatric Crohn's Disease Activity Index (PCDAI) for Crohn's disease
      and the Pediatric Ulcerative Colitis Disease Activity Index (PUCAI) for
      Ulcerative Colitis. In addition, we investigated F1+F2, TAT, TFPI and fibrinogen.
      RESULTS: There was a significant increase of endogenous thrombin potential (ETP),
      lag time and time to peak in patients with IBD, while peak showed no difference
      to healthy controls. ETP and F1+F2 in children with IBD also showed a significant
      correlation with PCDAI (PUCAI) and fibrinogen. CONCLUSION: IBD in children is
      associated with high TG, but this seems to be caused mainly by the inflammatory
      process and not by any individual disposition.

PMID- 19763359
TI  - No differences in support of thrombin generation by neonatal or adult platelets.
AB  - Newborns have, despite low clotting factors and poor in vitro platelet function,
      a well functioning hemostasis. The reason for this is still not completely clear.
      The aim of our study was to investigate whether phospholipids in neonatal
      platelets differ from those in adult platelets in their total amount, in their
      exposure on the platelet surface, and their effect on thrombin generation (TG).
      METHODS: Clotting times of newborn and adult platelet-rich plasma were measured.
      Effect of newborn and adult platelets on TG was measured by means of CAT
      (calibrated automated thrombography). In addition, the effect of newborn and
      adult platelets with or without stimulation by ionophor on TG was measured in a
      purified prothrombinase complex. Phosphatidylserine-exposure (PS) of newborn and
      adult platelets was measured by flow cytometry of annexin V binding. The amount
      of phospholipids (PL) was determined by means of mass spectrometry. RESULTS:
      Clotting times of platelet-rich plasma (PRP) of newborns stimulated with ionophor
      showed a significant lower reduction of clotting time than in adult PRP. No
      differences in the support of TG between neonatal and adult platelets were found
      in neonatal or adult plasma by means of CAT. In the purified system TG was
      increased by adding ionophor stimulated platelets but no difference was evident
      between stimulated newborn and adult platelets. Flow cytometric analysis showed
      no difference in annexin V binding between adult and newborn platelets. The
      results of mass spectrometry showed a very similar amount and pattern of PL of
      adult and newborns platelets. CONCLUSION: Our results do not provide any evidence
      that a different PL content or expression of neonatal platelets may alter TG in
      neonates.

PMID- 19763360
TI  - Screening for haemorrhagic disorders in paediatric patients by means of a
      questionnaire.
AB  - AIM: In children, screening for haemorrhagic disorders is further complicated by
      the fact that infants and young children with mild disease in many cases most
      likely will not have a significant history of easy bruising or bleeding making
      the efficacy of a questionnaire even more questionable. PATIENTS, METHODS: We
      compared the questionnaires of a group of 88 children in whom a haemorrhagic
      disorder was ruled out by rigorous laboratory investigation to a group of 38
      children with mild von Willebrand disease (VWD). Questionnaires about child,
      mother and father were obtained prior to the laboratory diagnosis on the occasion
      of routine preoperative screening. RESULTS: 23/38 children with mild VWD showed
      at least one positive question in the questionnaire, while 21/88 without
      laboratory signs showed at least one positive question. There was a trend to more
      specific symptoms in older children. Three or more positive questions were found
      only in VWD patients, but only in a few of the control group. The question about
      menstrual bleeding in mothers did not differ significantly. Sensitivity of the
      questionnaire for a hemostatic disorder was 0.60, while specifity was 0.76. The
      negative predictive value was 0.82, but the positive predictive value was only
      0.52. CONCLUSIONS: Our small study shows, that a questionnaire yields good
      results to exclude a haemostatic disorder, but is not a sensitive tool to
      identify such a disorder.

PMID- 19763361
TI  - Cross sectional study to investigate the influence of treatment regimes on the
      development of haemophilic arthropathy.
AB  - Haemophilic arthropathy is often present in patients with severe haemophilia. New
      studies demonstrate that only a small amount and a short exposure of blood in
      vitro are able to induce an impairment of the joint cartilage. Free blood in the
      joint leads to different mechanisms and includes cartilage and bone damage
      induced by a release of macrophages and monocytes followed by activated cytokines
      and inflammatory processes. Another mechanism is mediated by free iron resulting
      in synovitis and synovial hyperplasia and a neoangiogenesis on the base of VEGF
      release is common. At worst, these processes result in a complete picture of
      haemophilic arthropathy reducing quality of life. Few studies are available about
      the influence of factor treatment regime, e. g. prophylaxis or on-demand therapy,
      on the development of haemophilic arthropathy. However these studies investigated
      in most cases children. Therefore, it is still impossible to give recommendations
      for the right treatment in adult haemophilic patients because data are still
      lacking. For that reason, we attempt to initiate the HemArthro-Project to
      investigate the influence of treatment therapy on the development of arthropathy
      in adult haemophilic patients. This study includes the investigation of
      functional musculoskeletal parameters for the description of joint function in
      maximal 500 severe haemophilic patients parted into two groups of treatment
      regime (prophylaxis vs. on-demand). The investigators are seeking further
      assistance from the haemophilic treatment centers for the support of this study.

PMID- 19763362
TI  - Haemophilia registry of the medical committee of the swiss haemophilia society.
AB  - The Swiss Haemophilia Registry of the Medical Committee of the Swiss Haemophilia
      Society was established in 2000. Primarily it bears epidemiological and basic
      clinical data (incidence, type and severity of the disease, age groups, centres,
      mortality). Two thirds of the questions of the WFH Global Survey can be answered,
      especially those concerning use of concentrates (global, per capita) and
      treatment modalities (on-demand versus prophylactic regimens). Moreover, the
      registry is an important tool for quality control of the haemophilia treatment
      centres. There are no informations about infectious diseases like hepatitis or
      HIV, due to non-anonymisation of the data. We plan to incorporate the results of
      the mutation analysis in the future.

PMID- 19763363
TI  - Similarity in depressive symptom profile in a population-based study of migrants
      in the Netherlands.
AB  - OBJECTIVE: Depression is a clinical syndrome developed in Western Europe and
      North-America. The expression of symptoms and the impact of symptoms on
      functioning may therefore be expected to vary across cultures and languages. Our
      first aim was to study differences in depressive symptom profile between
      indigenous and non-Western immigrant populations in the Netherlands. We
      hypothesized that differences in expression of depressive symptoms would be more
      likely in the domains of mood and cognitions, and less likely in the domains of
      psychomotor and vegetative symptoms. Our second aim was to study ethnic
      differences in the association of depressive symptoms and general functioning.
      METHOD: In a random community sample stratified for ethnicity in Amsterdam, the
      Netherlands, depressive symptoms were assessed by bilingual interviewers using
      the Composite International Diagnostic Interview (CIDI 2.1) and the Symptom
      Checklist-90-Revised (SCL-90-R). Impairments in functioning were measured by the
      World Health Organization Disability Assessment Schedule II (WHODAS II). Results
      were obtained from 812 subjects: N = 321 native Dutch, N = 213 Turkish-Dutch, N =
      191 Moroccan-Dutch, N = 87 Surinamese-Dutch. Differences in depressive symptom
      expression were tested by differential item functioning. RESULTS: The prevalence
      of DSM-IV depressive disorder and the overall level of depressive symptoms were
      higher in the Turkish and Moroccan immigrant groups compared to native Dutch
      subjects. Ethnic differences in item functioning of depressive symptoms were
      rare, and equally unlikely in all four symptom domains. Depression was equally
      associated with functional impairment across ethnic groups. CONCLUSION: Although
      depressive symptoms were more common among migrants than in the indigenous
      population, both the depressive symptom profile and the associated functional
      impairments were comparable. These findings may help diminishing concerns about
      the validity of using existing diagnostic procedures among ethnic minority
      groups.

PMID- 19763364
TI  - Temporal relationships between Gulf War deployment and subsequent psychological
      disorders in Royal Australian Navy Gulf War veterans.
AB  - BACKGROUND: Although much has been published on the effects of the 1990/1991 Gulf
      War on the psychological health of veterans, few studies have addressed the
      pattern and timing of post-war development of psychological disorders. Our study
      aims to identify the most common psychological disorders that first appeared post
      Gulf War, the period of peak prevalence and the sequence of multiple
      psychological disorders. METHODS: The temporal progression of psychological
      disorders in male Australian naval Gulf War veterans with no prior psychological
      disorders was calculated across each year of the post-Gulf War period. DSM-IV
      diagnoses were obtained using the Composite International Diagnostic Interview.
      RESULTS: Psychological disorder rates peaked in the first 2 years (1991-1992)
      following the Gulf War. Alcohol use disorders were the most likely to appear
      first. Classification and regression tree analysis found that risk of disorder
      was exacerbated if veterans had been exposed to a high number of potential
      psychological stressors during their military service. Lower military rank was
      associated with increased risk of alcohol disorders, particularly during the
      first 2 years post-Gulf War. In veterans with two or more disorders, anxiety
      disorders and alcohol disorders tended to appear before affective disorders.
      CONCLUSIONS: Our study found that psychological disorders occur in sequence
      following Gulf War deployment. Our findings may help clinicians to anticipate,
      and better manage, multiple symptomatology. The findings may also assist veteran
      and defence organisations in planning effective mental health screening,
      management and prevention policy.

PMID- 19763365
TI  - Suicide and marital status in Northern Ireland.
AB  - INTRODUCTION: Studies show marriage to be protective against suicide though with
      variation in the extent to which suicide rates are higher among the never
      married, separated or divorced and widowed. We examined suicide in Northern
      Ireland by marital status and examined whether the observed variation differed by
      sex and age. METHODS: Data relating to all 1,398 suicide deaths (ICD-9 E950-959
      and ICD-10 X60-84) registered in 1996-2005 were analysed using Poisson
      regression. RESULTS: The total, male and female age-standardised suicide rates
      were 8.4, 13.6 and 3.3 per 100,000, respectively. Never marrying increased male
      suicide risk and its effect increased with age (incidence rate ratio (IRR) among
      20-34 year-olds = 1.47, 95% confidence interval (CI) = 1.19-1.84; IRR among over
      55 year-olds = 2.33, 95% CI = 1.55-3.50). Never marrying was a risk factor for
      women only if aged 20-34 years (IRR = 3.05, 95% CI = 1.70-5.47). Among over 55
      year-olds, widowhood increased risk of male suicide only (IRR = 2.47, 95% CI =
      1.64-3.70) whereas divorce was associated with an almost threefold increase in
      male (IRR = 2.61, 95% CI = 1.39-4.88) and female (IRR = 2.57, 95% CI = 0.89-7.42)
      suicide relative to married persons. The effect of divorce was far more
      pronounced in 20-34 year-old men (IRR = 5.59, 95% CI = 3.58-8.67) and women (IRR
      = 9.46, 95% CI = 3.81-23.37). CONCLUSIONS: In Northern Ireland, marriage protects
      both sexes against suicide though men more so than women. Divorced young men, in
      particular, are a population at high risk of suicide.

PMID- 19763366
TI  - Reoperation rate for traditional anterior vaginal repair: analysis of 207 cases
      with a median 4-year follow-up.
AB  - INTRODUCTION AND HYPOTHESIS: To determine the reoperation rate for symptomatic
      recurrence of cystoceles following traditional anterior colporrhaphy (without
      mesh). METHODS: Retrospective case note review of 207 cases of primary anterior
      colporrhaphy with/without other prolapse surgery. All patients received a 3-month
      clinic follow-up. Reoperation details for prolapse and/or urinary incontinence
      were obtained from patients general practitioners with a median follow-up of 50
      months. RESULTS: The median age was 60 years (32-85), and median parity was 2.
      Twenty-nine of 207 (14%) patients had previous gynecological surgery. While the
      anatomical recurrence rate of cystoceles at 3 months postoperatively was 12%, the
      reoperation rate for recurrent cystocele by 50 months was 3.4%. Overall, 9.1% of
      the group underwent prolapse or incontinence surgery during this period.
      CONCLUSIONS: While the anatomical recurrence rates for cystocele following
      traditional anterior colporrhaphy might be high, the low reoperation rate at more
      than 4 years (3.4%) suggests that patient's symptoms might not be bothersome
      enough to require further surgery. Both subjective and anatomical outcomes are
      required to assess the outcome of both traditional and new prolapse procedures.

PMID- 19763367
TI  - Validation of the Slovakian version of the P-QOL questionnaire.
AB  - INTRODUCTION AND HYPOTHESIS: This study aimed to validate the Slovakian version
      of the prolapse quality-of-life (P-QOL) questionnaire. METHODS: The P-QOL
      questionnaire was translated into the Slovakian language and administered to
      women recruited from a urogynecology outpatient clinic at a tertiary referral
      teaching hospital. After completing a questionnaire, all women were examined in
      supine position using the Pelvic Organ Prolapse (POP-Q) Quantification system.
      The reliability was assessed by using a 2-week test-retest analysis. RESULTS:
      Fifty symptomatic and 79 asymptomatic women were included. The score of P-QOL was
      strongly correlated with the vaginal examination findings among the symptomatic
      group (p < 0.001 in eight domains). P-QOL domain scores were significantly
      different between symptomatic and asymptomatic women. The test-retest reliability
      confirmed a highly significant correlation between the total scores for each
      domain (p < 0.001). CONCLUSION: The Slovakian version of the P-QOL questionnaire
      is a valid, reliable, and easily comprehensible instrument to assess quality of
      life of women with uterovaginal prolapse.

PMID- 19763368
TI  - Is lysyl oxidase-like protein-1, alpha-1 antitrypsin, and neutrophil elastase
      site specific in pelvic organ prolapse?
AB  - INTRODUCTION AND HYPOTHESIS: We investigated whether the expression of alpha-1
      antitrypsin (ATT), neutrophil elastase (NE), and lysyl oxidase-like protein 1
      (LOXL-1) vary within the vagina in subjects with pelvic organ prolapse (POP).
      METHODS: Biopsies were obtained from the anterior and posterior vaginal wall of
      22 women with POP (> or =stage 2 by POP-Q). The subjects were grouped by the most
      prominent defect: cystocele, cystocele plus uterine prolapse, and rectocele.
      Comparative real-time PCR, Western blotting, and NE enzyme activity assay were
      performed. RESULTS: The ratio of anterior and posterior vaginal wall ATT, NE, and
      LOXL-1 expression varied between individuals within the same defect group.
      CONCLUSIONS: ATT, NE, and LOXl-1 expression was variable among different biopsy
      sites in the vagina. No consistent pattern was present when the subjects were
      grouped by the most prominent defect. We recommend careful consideration of
      biopsy sites in future studies on POP to enhance reproducibility of data.

PMID- 19763370
TI  - Transplanted chondrocytes inhibit endochondral ossification within cartilage
      repair tissue.
AB  - The aim of this study was to investigate the effect of transplanted chondrocytes
      on endochondral bone formation in cartilage repair tissue. In the knee joint of
      miniature pigs, cartilage lesions were treated by microfracturing and were then
      either left empty, covered with a collagen membrane, or treated by matrix
      associated autologous chondrocyte transplantation. In control lesions, the
      subchondral bone plate was left intact (partial-thickness lesion). The repair
      tissues were analyzed after 12 weeks by histological methods focusing on bone
      formation and vascularization. The effect of chondrocytes on angiogenesis was
      assessed by in vitro assays. The presence of antiangiogenic proteins in cartilage
      repair tissue, including thrombospondin-1 (TSP-1) and chondromodulin-I (ChM-I),
      was detected immunohistochemically and their expression in chondrocytes and bone
      marrow stromal cells was measured by quantitative RT-PCR. Significant outgrowths
      of subchondral bone and excessive endochondral ossification within the repair
      tissue were regularly observed in lesions with an exposed or microfractured
      subchondral bone plate. In contrast, such excessive bone formation was
      significantly inhibited by the additional transplantation of chondrocytes.
      Cartilaginous repair tissue that resisted ossification was strongly positive for
      the antiangiogenic proteins, TSP-1 and ChM-I, which were, however, not detectable
      in vascularized osseous outgrowths. Chondrocytes were identified to be the major
      source of TSP-1- and ChM-I expression and were shown to counteract the angiogenic
      activity of endothelial cells. These data suggest that the resistance of
      cartilaginous repair tissue against endochondral ossification following the
      transplantation of chondrocytes is associated with the presence of antiangiogenic
      proteins whose individual relevance has yet to be further explored.

PMID- 19763371
TI  - Endostatin affects osteoblast behavior in vitro, but collagen XVIII/endostatin is
      not essential for skeletal development in vivo.
AB  - Endostatin, a fragment of collagen XVIII, can inhibit vascular endothelial growth
      factor (VEGF) signaling. VEGF is known to be crucial for bone development. The
      aims of this study were to investigate the influences of endostatin on osteoblast
      behavior in vitro and the roles of collagen XVIII/endostatin on bone development
      in vivo. For the in vitro experiments, MC3T3-E1 osteoblasts were treated with
      VEGF-A, 2 microg/ml endostatin, 20 microg/ml endostatin, VEGF-A + 2 microg/ml
      endostatin, or VEGF-A + 20 microg/ml endostatin. Osteoblast proliferation and
      matrix mineralization were analyzed. Faxitron, pQCT, and histological analyses
      were performed on hindleg bones of transgenic mice overexpressing endostatin (ES
      tg) and mice lacking collagen XVIII (Col18a1 (-/-)) to study bone development in
      vivo. Treatment of cells with endostatin decreased osteoblast proliferation.
      Moreover, VEGF-A together with endostatin (2 microg/ml) decreased osteoblast
      proliferation and matrix mineralization. In vivo, Col18a1 (-/-) and ES-tg mice
      displayed no differences in bone density or mineral content during bone
      development, but ES-tg bones grew in length more slowly compared to the controls.
      The formation of secondary ossification centers was delayed in Col18a1 (-/-)
      mice. Immunohistochemistry revealed collagen XVIII in basement membranes of
      periosteal and bone marrow vessels and at muscle attachment sites. In conclusion,
      endostatin affects osteoblast behavior in vitro, the effects being boosted by
      simultaneous treatment with VEGF. In vivo, Col18a1 (-/-) and ES-tg mice show mild
      delays in bone development. These changes are transitory and suggest that
      collagen XVIII/endostatin does not play an indispensable role in skeletal
      development.

PMID- 19763372
TI  - Bone seeking labels as markers for bone turnover: effect of dosing schedule on
      labeling various bone sites in rats.
AB  - Urinary excretion of bone labels can be used to monitor bone resorption. Here we
      investigate the effects of dosing frequency on label incorporation of various
      sites when bone turnover was perturbed by ovariectomy. We compared tritiated
      tetracycline ((3)H-TC) and (45)Ca in two studies. Nine-month-old rats were given
      single or multiple injections of (3)H-TC and (45)Ca and sacrificed after 7 or 14
      days. Six-month-old OVX rats were given (3)H-TC and (41)Ca tracers 1 or 3 months
      following ovariectomy (OVX + 1 mo or OVX + 3 mo, when bone turnover was higher or
      lower, respectively) and sacrificed 1 week, 1 month, 3 months, or 6 months
      postdose. Twenty-four-hour urine pools over 2-4 consecutive days as well as the
      proximal tibia, femur midshaft, lumbar vertebrae (L1-L4), and remaining skeleton
      were analyzed for (3)H, (45)Ca, and calcium content. Bone turnover as assessed by
      urinary (3)H-TC was greater in OVX + 1 mo compared to OVX + 3 mo rats up to 6
      months postdose. (45)Ca labeling efficiency (% dose/g Ca) was significantly
      higher than for (3)H and labeling was higher in trabecular-rich than cortical
      rich bone. This study affirms that a single administration of either (3)H-TC or
      (45)Ca is a useful approach to measuring bone turnover directly. The amount of
      label incorporation into bone was greater in bone sites that were more
      metabolically active and in all sites when closer vs farther from OVX.

PMID- 19763373
TI  - Elevated serum PTH is independently associated with poor outcomes in older
      patients with hip fracture and vitamin D inadequacy.
AB  - To determine whether serum 25(OH)D and/or PTH levels in older patients with hip
      fracture (HF) could predict short-term clinical outcomes, we conducted a
      prospective observational study of 287 consecutive HF patients (mean age 81.9 +
      or - 7.5 [SD] years, 72% females). The prevalence of vitamin D inadequacy
      (25[OH]D < 80 nmol/l) was 97.1%, that of vitamin D deficiency (25[OH]D < 50
      nmol/l) was 79.8%, and that of elevated PTH level (>6.8 pmol/l) was 35.5%. After
      adjustment for age and sex, PTH was significantly associated with in-hospital
      mortality (OR = 1.12, 95% CI 10.5-1.20, P < 0.001), myocardial injury (OR = 1.05,
      95% CI 1.03-1.15, P = 0.002), prolonged length of stay (LOS > or = 20 days; OR =
      1.05, 95% CI 1.01-1.06, P = 0.044), and being discharged to institutional care
      (OR = 1.07, 95% CI 1.01-1.18, P = 0.48). Secondary hyperparathyroidism (SHPT),
      but not vitamin D deficiency, was associated with older age, a higher prevalence
      of trochanteric fracture, coronary artery disease, hypertension, previous stroke,
      renal impairment, increased levels of serum osteocalcin, bone-specific alkaline
      phosphatase, and adiponectin as well as a significantly higher in-hospital
      mortality (11.8 vs. 0.54%, P = 0.001), perioperative myocardial injury (32.7 vs.
      22.5%, P = 0.043), LOS > or = 20 days (40.2 vs. 26.9%, P = 0.017), and being
      discharged to institutional care (29.5 vs. 14.6%, P = 0.019). In multivariate
      regression analyses, SHPT was strongly associated with in-hospital mortality and
      LOS > or = 20 days. We conclude that elevated PTH (but not vitamin D deficiency
      per se) is a strong independent predictor of poor outcomes in older patients.

PMID- 19763374
TI  - Marrow stromal cell-based cyclooxygenase 2 ex vivo gene-transfer strategy
      surprisingly lacks bone-regeneration effects and suppresses the bone-regeneration
      action of bone morphogenetic protein 4 in a mouse critical-sized calvarial defect
      model.
AB  - This study evaluated whether the murine leukemia virus (MLV)-based cyclooxygenase
      2 (Cox-2) ex vivo gene-transfer strategy promotes healing of calvarial defects
      and/or synergistically enhances bone morphogenetic protein (BMP) 4-mediated bone
      regeneration. Gelatin scaffolds impregnated with mouse marrow stromal cells
      (MSCs) transduced with MLV-expressing BMP4, Cox-2, or a control gene were
      implanted into mouse calvarial defects. Bone regeneration was assessed by X-ray,
      dual-energy X-ray absorptiometry, and histology. In vitro, Cox-2 or
      prostanglandin E(2) enhanced synergistically the osteoblastic differentiation
      action of BMP4 in mouse MSCs. In vivo, implantation of BMP4-expressing MSCs
      yielded massive bone regeneration in calvarial defects after 2 weeks, but the Cox
      2 strategy surprisingly did not promote bone regeneration even after 4 weeks.
      Staining for alkaline phosphatase (ALP)-expressing osteoblasts was strong
      throughout the defect of animals receiving BMP2/4-expressing cells, but defects
      receiving Cox-2-expressing cells displayed weak ALP staining along the edge of
      original intact bone, indicating that the Cox-2 strategy lacked bone-regeneration
      effects. The Cox-2 strategy not only lacked bone-regeneration effects but also
      suppressed the BMP4-induced bone regeneration. In vitro coculture of Cox-2
      expressing MSCs with BMP4-expressing MSCs in gelatin scaffolds reduced BMP4 mRNA
      transcript levels, suggesting that Cox-2 may promote BMP4 gene silencing in BMP4
      expressing cells, which may play a role in the suppressive action of Cox-2 on
      BMP4-mediated bone formation. In summary, the Cox-2 ex vivo gene-transfer
      strategy not only lacks bone-regeneration effects but also suppresses the bone
      regeneration action of BMP4 in healing of calvarial defects.

PMID- 19763375
TI  - Effect of the vitamin D receptor on bone geometry and strength during gestation
      and lactation in mice.
AB  - The vitamin D receptor (VDR) plays an important role in maintaining calcium
      homeostasis, acting as a mediator of transcellular calcium absorption and bone
      remodeling. Mice lacking a functional VDR have an abnormal skeletal phenotype,
      which is rescued by feeding a high-calcium diet. In this study, the role of the
      VDR in maintaining bone geometry and strength during gestation and lactation,
      when increased demands are placed on the calcium regulatory channels, was
      examined using a knockout mouse model. A rescue diet was used to counteract the
      decrease in calcium absorption in the gut that results from the absence of the
      VDR. Structural and compositional characteristics of the femur were compared
      between VDR knockout and wild-type mice following 9 and 16 days of gestation and
      5 and 10 days of lactation using generalized linear models. Overall, the knockout
      mice had 6.5% lower cortical area, 23% lower trabecular volume fraction, and 9%
      lower bending stiffness than wild-type mice. However, the maximum moment of
      inertia of the femoral diaphyses, ultimate bending load, ash fraction, and
      trabecular thickness were not significantly different between knockout and wild
      type mice. Only the mineral content exhibited interdependence between genotype
      and time point. Taken together, the results show that the VDR affects the
      quantity of mineralized bone tissue in the femoral diaphysis and metaphysis
      independently of reproductive status. However, the moments of inertia were
      similar between genotypes, resulting in similar bone stiffness and strength
      despite lower mineral content and cross-sectional area.

PMID- 19763376
TI  - Treatment with a potent cathepsin K inhibitor preserves cortical and trabecular
      bone mass in ovariectomized monkeys.
AB  - The cysteine protease cathepsin K is involved in osteoclast-mediated bone
      resorption. We evaluated the effect of daily oral dosing of an inhibitor of human
      cathepsin K (SB-462795 [relacatib]) for 9 months on bone turnover, mass, and
      architecture in estrogen-deficient cynomolgus monkeys. Ovariectomized animals
      were treated orally with relacatib at 1, 3, or 10 mg/kg/day, or oral vehicle plus
      alendronate at 0.05 mg/kg by IV injection once every 2 weeks. The control groups,
      ovariectomized and sham-ovariectomized animals, received vehicle (all groups n =
      20 animals). Samples for biomarker analysis were collected at various times, bone
      mass changes were evaluated at 6 and 9 months of treatment, and histomorphometric
      analysis was performed at 9 months. Relacatib significantly reduced urinary N
      telopeptide excretion within 1 week of treatment at all dose levels, an effect
      that was maintained at the highest dose level. At some time points bone formation
      markers were elevated at the lowest dose of relacatib. Animals treated with
      relacatib had dose-dependent preservation of areal bone mineral density reaching
      statistical significance in distal femur. In femur neck there was significant
      preservation of total volumetric BMD (vBMD) by relacatib. By histomorphometry,
      relacatib reduced indices of bone resorption and formation at cancellous sites as
      did alendronate. In cortical bone, osteonal bone formation rate was reduced by
      alendronate but preserved at low and medium doses of relacatib. Thus, relacatib
      preserved cortical and cancellous bone mass in ovariectomized monkeys.

PMID- 19763377
TI  - Significant association of fracture of the lumbar spine with mortality in female
      hemodialysis patients: a prospective observational study.
AB  - Prevalent fracture of the lumbar spine is established as a predictor of increased
      mortality in the general population. To examine whether this association is
      retained in hemodialysis patients, we conducted a single-center prospective
      observational study in 635 hemodialysis patients (60.3 + or - 12.0 years old,
      male/female 369/266). Patients were divided into two groups (with and without
      lumbar fracture, assessed by simple lateral radiograph), and survival was
      followed for an average of 53.8 months. Lumbar fracture was present in 62
      patients (9.76%; male 9.76%, female 9.77%). During the follow-up period, there
      were 176 all-cause deaths (27.7%; male 27.6%, female 27.8%), of which 72 were
      from cardiovascular diseases. In Kaplan-Meier analysis, all-cause and
      noncardiovascular mortality rates, but not cardiovascular mortality, were
      significantly higher in patients with fracture than in those without (P <
      0.0001). In multivariate Cox proportional hazard analysis, the presence of lumbar
      fracture was significantly associated with increased noncardiovascular mortality
      (HR = 2.035, 95% CI 1.135-3.652, P < 0.05) after adjustment for age, duration of
      hemodialysis, presence of diabetes, body mass index, and serum calcium,
      phosphate, and albumin. Significantly higher all-cause and noncardiovascular
      mortality rates were also evident for patients with fracture in separate analyses
      in males and females, but multivariate analysis showed a significant association
      of lumbar fracture with increased all-cause (HR = 2.151, 95% CI 1.033-4.478, P <
      0.05) and noncardiovascular (HR = 2.637, 95% CI 1.014-6.858, P < 0.05) mortality
      rates only in females. In conclusion, lumbar fracture is significantly associated
      with all-cause mortality in female patients.

PMID- 19763378
TI  - Bone turnover and the osteoprotegerin-RANKL pathway in tumor-induced
      osteomalacia: a longitudinal study of five cases.
AB  - To evaluate serum levels of osteoprotegerin (OPG), soluble receptor activator of
      the nuclear factor-kappaB (RANKL), and their relationship with FGF-23, lumbar
      bone mineral density (BMD), and bone turnover markers, five patients with tumor
      induced osteomalacia (TIO) and 40 healthy controls were studied. TIO patients
      were followed for 360 days after surgical removal of underlying tumor (n = 2) or
      beginning of therapy with phosphate and calcitriol when surgical treatment was
      impossible (n = 3). At diagnosis, TIO patients had higher levels of FGF-23 and
      bone-specific alkaline phosphatase (bALP) and lower levels of cathepsin K
      (CathK), RANKL, and RANKL/OPG ratio compared to controls. During the follow-up,
      FGF-23 decreased significantly only in patients who underwent a surgical
      excision, while phosphate and BMD increased in all patients. The increases in
      BMD, phosphate, and renal phosphate reabsorption rate were directly related. In
      the first 60 days of follow-up, we observed a prolonged inhibition of RANKL,
      CathK, and bone resorption markers associated with a persistence of TIO symptoms
      and an increase in bALP. From day 60, levels of bone turnover markers returned
      progressively within the normal range and a clinical remission was observed. The
      inhibition of the RANKL/OPG pathway and the uncoupling of bone formation and
      resorption observed in patients with active TIO may be a compensatory mechanism,
      attempting to reduce worsening of osteomalacia. The BMD increase during TIO
      treatment is related to the improvement of phosphate rather than FGF-23 levels. A
      "hungry bone"-like syndrome was observed after surgical or pharmacological
      treatment.

PMID- 19763379
TI  - Functional cervical MRI within the scope of whiplash injuries: presentation of a
      new motion device for the cervical spine.
AB  - PURPOSE: Frequently following a whiplash injury of the cervical spine, patients
      suffer from persistent pain symptoms. The MRI will in some of these cases show
      changes consistent with disk pathology or spinal stenosis, although in most
      instances the imaging studies will offer no adequate explanation for the
      described symptoms. The goal of our research was to develop and test a new MRI
      compatible device that will allow functional imaging of the cervical spine.
      METHODS: A total of 30 patients with whiplash injuries were evaluated during the
      first 6 weeks following trauma with the functional MRI. The examination was
      carried out with a T2-weighted turbo spin-echo sequence utilizing a new apparatus
      consisting of an inflatable air bag contained in a Plexiglas housing. Thanks to a
      valve placed outside of the examination room, it was possible to individually
      regulate the amount of air used to fill the pillow, thereby obtaining a full
      range of motion between flexion and extension. RESULTS: In 25 cases no pathology
      was found during this examination. Two patients presented with scarring of the
      alar ligaments, indicative of a traumatic lesion. In two other instances the
      images in reclination revealed a bulging disk, while in one case a widening of
      the disk space was found as a sign for a rupture of the anterior longitudinal
      ligament. CONCLUSION: Our study was able to demonstrate the applicability of the
      new functional testing device, which permits a standardized, continuous and
      dynamic evaluation of the cervical spine in a closed MRI.

PMID- 19763380
TI  - An unreported anatomical finding: unusual insertions of the stylohyoid and
      digastric muscles.
AB  - The presence of a unusual appearance of the stylohyoid and digastric muscles may
      lead to a confusion in some pathological cases, during the radiological
      examination and aesthetic facial surgery. These differences may cause pharyngeal
      pain and foreign body sensation in the throat. During the dissection, unusual
      insertions, origin, insertion, shape and bilaterality were investigated in 28
      cadavers' heads. In a total of 56, the presence of unusual insertions which
      belong to the stylohyoid muscle were observed in 22 sides (39.3%), and atypical
      fibers which belong to the digastric muscle were observed in 39 sides (69.6%).
      Bilaterality of the presence of atypical appearance was observed for stylohyoid
      and digastric muscles, in 10 (35.7%) and 19 (67.8%) specimens, respectively. In
      12 heads (42.9%), atypical fibers, the stylohyoid and the digastric coexisted.
      These fibers which were shaped like a circular spiral were realized to have the
      shape of an arch or circle in front of the hyoid bone. The posterior bellies of
      the digastric muscle, the mylohyoid and the remaining suprahyoid muscles of both
      sides were normal. The unusual insertion of the stylohyoid muscles which cover
      the hyoid bone as a collar was not described in the classification of the
      previous studies. These fibers may give an variant mobility to the hyoid and they
      occur depending on the differences in the stylohyoid chains. Although the styloid
      process was in normal size, unusual insertions of the stylohyoid muscle that
      cover the hyoid as a belt or collar may give symptoms similar to those of the
      stylohyoid syndrome.

PMID- 19763381
TI  - Diagnostic value of history, physical examination and needle electromyography in
      diagnosing lumbosacral radiculopathy.
AB  - To examine the diagnostic value of history, physical examination and needle EMG
      in predicting nerve root compression on MRI in patients with clinical suspicion
      of lumbosacral radicular syndrome (LSRS). Subjects comprised 202 consecutive
      patients from January 2006 to March 2007 with suspicion of LSRS referred by
      general practitioners. Clinical evaluation consisted of history, physical
      examination, EMG and MRI. Bivariate and multiple logistic regression analyses
      were used to calculate the diagnostic value of each test item compared to
      radiological nerve root compression. 95 patients (47%) had radiological nerve
      root compression. Significant predictors of radiological nerve root compression
      were dermatomal radiation [odds ratio (OR) 2.1], more pain on coughing, sneezing
      or straining (OR 2.4), positive straight leg raising (OR 3.0) and ongoing
      denervation on EMG (OR 4.5). 15 patients (7%) had ongoing denervation on EMG
      without radiological nerve root compression. In clinical practice, dermatomal
      radiation, more pain on coughing, sneezing or straining, positive straight leg
      raising and ongoing denervation on EMG may be used to predict nerve root
      compression on MRI. EMG may also be of additional value in patient with clinical
      suspicion of lumbosacral radicular syndrome without nerve root involvement on
      MRI.

PMID- 19763382
TI  - Choreathetosis due to abuse of levothyroxine.
AB  - Choreathetosis due to thyrotoxicosis is a rare movement disorder of acute onset.
      Here we present the first report of choreathetosis secondary to abuse of
      levothyroxine. A 35-year-old woman with autoimmune thyroiditis tripled her daily
      levothyroxine intake and lost 20 kg of weight during the following 6 months. She
      soon developed incapacitating choreathetosis. When levothyroxine was reduced to
      her usual dosage, all symptoms vanished in 7 days. The prompt effect of dose
      correction points towards a direct influence of levothyroxine on the basal
      ganglia; alternatively, the effects of levothyroxine might have been indirect
      and, possibly, autoimmune-mediated. Abuse of levothyroxine and related thyroid
      tropic substances should be included into the differential diagnosis of acute
      choreathetosis.

PMID- 19763383
TI  - Idiopathic mesial temporal lobe epilepsy: a syndrome with complex inheritance?

PMID- 19763384
TI  - Botulinum toxin type A and a rehabilitation program in the treatment of Pisa
      syndrome in Parkinson's disease.

PMID- 19763385
TI  - Influence of pregnancy in the behavior of diffuse gliomas: clinical cases of a
      French glioma study group.
AB  - Advances in the understanding of the natural history of diffuse low-grade gliomas
      and the optimization of their therapeutic management have allowed an improvement
      of their prognosis. Therefore, more and more young women harboring such gliomas
      now envision a pregnancy. However, relationships between gliomas and pregnancy
      are poorly known. We performed a retrospective review of all observed pregnancies
      in the adult female population of supra-tentorial hemispheric gliomas followed by
      a French glioma study group. Clinical, imaging and pathological findings were
      reviewed. In the present case studies, eight pregnancies in eight females were
      observed in a total of 443 adult females diagnosed between 1992 and 2007. Glioma
      was diagnosed before pregnancy in five patients and during pregnancy in three
      patients. In six cases, pregnancy appears as having possible negative interaction
      with the tumor, such as clinical worsening, tumor changes in imaging and
      histological findings. In two cases, pregnancy appears as having no effect in the
      natural history of the tumor. The present results suggest a possible negative
      interaction between pregnancy and diffuse gliomas. We thus propose informing the
      patient about the possible risks of tumor growth increase and of malignant
      transformation during pregnancy. In the presence of such a tumor, a pregnancy may
      reasonably be envisioned, but the benefit-to-risk ratio should be carefully
      weighed and discussed. If a pregnancy is decided, we thus advise performing a
      very close neurological follow-up with repeated control MRIs in addition to
      rigorous obstetrical monitoring.

PMID- 19763386
TI  - Laparoscopic liver surgery: 8 years of multicenter Spanish register.
AB  - BACKGROUND: To present the data of laparoscopy in liver surgery and to assess the
      real indications and outcomes of this kind of approach. METHODS: From February
      2000 to March 2008, a prospective study was performed on 182 patients from 15
      Spanish surgical centres. RESULTS: A total of 308 lesions was collected. The mean
      age was 57 years old, and 61.5% were female. Among patients with cystic lesions
      we found: 45 simple cysts, 19 policystic diseases, 12 hydatidic cysts and 2
      cystoadenomas. Among solid lesions (n = 104), we found 34 patients with benign
      pathology (12 focal nodular hyperplasia, 10 adenomas, 7 haemangyomas and 5 other
      lesions) and 70 with malignant pathology (38 metastases, 29 hepatocellular
      carcinomas, 2 cholangiocarcinomas and 1 lymphoma). The global rate of conversion
      was 8.8%. The global morbidity rate was 14.8%, and 5 of them required re
      intervention. CONCLUSIONS: Nowadays there are strong criteria for patients being
      submitted to laparoscopy procedures based both on type and location features. The
      postoperative morbidity rate is low, also for hepatocellular carcinoma in
      cirrhotic liver. In case of malignant pathology, we think the use of
      ultrasonography is mandatory to obtain a free margin, which implies a long-term
      survival rate.

PMID- 19763387
TI  - Liver transplantation for hepatocellular carcinoma: the Japanese experience.
AB  - Despite the wide spectrum of selection criteria used by living donor liver
      transplantation (LDLT) centers in Japan, LDLT for hepatocellular carcinoma (HCC)
      can achieve an acceptable outcome comparable to the outcome for deceased donor
      liver transplantation (DDLT) for HCC. One of the most crucial considerations in
      liver transplantation for HCC is the advent of expanded criteria that allow more
      patients with HCC to receive the organs and offer similar or even better results
      compared to the Milan of UCSF criteria. Expanded criteria for HCC are proposed
      from three single-center and one multicenter study in Japan. These criteria are
      based on the independent predictors for outcome derived from the analyses of the
      pretransplant factors and explant pathology. The beneficial effect of those
      proposed criteria can be predicted by the inclusion rates of the patients
      compared to the Milan or UCSF criteria in the same cohort and the outcome for
      those included patients. While application of the UCSF criteria increases the
      inclusion rate compared to the Milan criteria by 5-10%, these proposed criteria
      increase the inclusion rates by 5-54% compared to the Milan criteria. The higher
      inclusion rates compared to the application of the Milan criteria are achieved by
      criteria including tumor markers, either AFP or PIVKA II or both. Inclusion of
      tumor markers in addition to parameters of tumor morphology might be the key to
      establish the best criteria for liver transplantation for HCC.

PMID- 19763388
TI  - Retrospective analysis on the management of anticoagulants and antiplatelet
      agents for scheduled endoscopy.
AB  - BACKGROUND: The guideline on the management of anticoagulants and antiplatelet
      agents for endoscopic procedures was established by the Japan Gastroenterological
      Endoscopy Society in 2005. However, the degree to which this guideline has
      reached prescribing doctors in other fields has not, so far, been evaluated.
      METHOD: Medical records of all patients who underwent scheduled endoscopy from
      January 2008 to December 2008 in the Department of Gastroenterology at the
      University of Tokyo were investigated retrospectively. RESULTS: Among 8921
      patients underwent scheduled endoscopy, 1383 patients (15.5%) were receiving
      anticoagulants or antiplatelet agents. 324 patients (23.4%) were receiving
      warfarin as an anticoagulant. The most common antiplatelet agent was aspirin in
      884 patients (63.9%), followed by ticlopidine in 150 patients (10.8%). Most
      patients taking warfarin alone (51.6%) or a combination of aspirin and
      ticlopidine (68.4%) underwent endoscopy without cessation. In contrast, most
      patients taking aspirin alone (46.0%) or ticlopidine alone (56.3%) underwent
      endoscopy after a cessation period of 6-7 days, indicating the low permeation of
      the cessation policy recommended in the guideline. Among 556 patients underwent
      endoscopy without a cessation period, 41 patients (7.4%) underwent invasive
      procedures including endoscopic mucosal resection. No bleeding complications were
      observed in patients who underwent invasive procedures without a cessation
      period. CONCLUSION: We revealed the low permeation of the guideline to
      prescribing doctors. Cessation before endoscopy to avoid bleeding complications
      can be dispensable.

PMID- 19763389
TI  - Long-term outcome of endoscopic and/or percutaneous transhepatic therapy in
      patients with biliary stricture after orthotopic liver transplantation.
AB  - BACKGROUND: Biliary strictures are a serious complication after liver
      transplantation. Endoscopic and percutaneous transhepatic procedures have gained
      an increasing potential for the management of this problem. OBJECTIVE: Long-term
      follow-up of endoscopic and/or percutaneous transhepatic therapy of biliary
      strictures after liver transplantation was evaluated. PATIENTS AND METHODS:
      Between January 1996 and December 2007, 47 patients with biliary stricture after
      liver transplantation were identified by analysing the endoscopic database,
      hospital charts and cholangiograms. Long-term follow-up was evaluated using
      cholangiograms, transabdominal ultrasound, laboratory parameters and physical
      examination. RESULTS: The type of biliary stricture after liver transplantation
      was subdivided into anastomotic stricture (n = 29), non-anastomotic stricture (n
      = 14) and bilioenterostomy stricture (n = 4). Of the patients, 38/47 were treated
      by endoscopic procedures (ERCP), and 9/47 patients were treated by percutaneous
      transhepatic procedures (PTBD). In 2 of 47 patients combined approaches
      (rendezvous technique) were performed. Overall, 23/29 patients in the anastomotic
      group, 12/14 patients in the non-anastomotic group, and 3/4 patients in the
      bilioenterostomy group had successfully completed endoscopic and/or percutaneous
      transhepatic therapy. Biliary drainage could be respectively terminated after
      median 9 (1-83), 11 (1-89) and 10 (4-14) months. CONCLUSIONS: Endoscopic as well
      as percutaneous transhepatic approaches in combination or as monotherapy are
      effective in the management of anastomotic and non-anastomotic strictures after
      liver transplantation.

PMID- 19763390
TI  - Effects of intermittent high glucose on oxidative stress in endothelial cells.
AB  - The objective of this study is to explore the mechanism of oxidative stress
      induced by intermittent high glucose in porcine iliac endothelial cells (PIECs).
      The PIECs were exposed to intermittent or constant high glucose for 3 or 6 days,
      and the mean fluorescent intensity (MFI) was measured via intracellular reactive
      oxygen species (ROS) captured by flow cytometry. The NADPH oxidase activity was
      measured by chemiluminescence with lucigenin. Intermittent high glucose induced a
      greater over-production of ROS than constant high glucose in PIECs; the NADPH
      oxidase activity was increased under both constant and intermittent high glucose
      conditions, being more marked in the latter (P < 0.05). In conclusion,
      intermittent high glucose induced more ROS in PIECs than constant high glucose,
      this effect seemed to be, at least in part related to the enhanced activation of
      NADPH oxidase. Glucose fluctuation may be involved in the development of vascular
      complications.

PMID- 19763391
TI  - Sacrococcygeal extraspinal ependymoma.

PMID- 19763392
TI  - Spinal cord compression due to an extra-dural intra-vascular papillary
      endothelial hyperplasia of the thoracic spine.
AB  - We present a case of spinal cord compression in a 33-year-old male due to a T6-T7
      paravertebral mass extending through the intervertebral foramen into the
      vertebral canal. Histopathological feature was consistent with an intra-vascular
      papillary endothelial hyperplasia. Differential diagnosis of the lesion and
      review of the literature are presented.

PMID- 19763393
TI  - Education and self-reported health care seeking behaviour in European welfare
      regimes: results from the European Social Survey.
AB  - OBJECTIVES: This study investigates educational inequalities in the perception of
      need for seeking health care in 24 European countries belonging to five different
      welfare regimes (Scandinavian, Anglo-Saxon, Bismarckian, Eastern and Southern).
      METHODS: Based on the European Social Survey Round 2 (N = 38,122), associations
      between years of education and intended doctor consultation in case of four
      hypothetical symptoms (backache, sore throat, sleeping problems and headache) are
      analysed by multiple logistic regressions. RESULTS: People with less years of
      education tend to be more likely to consult a doctor compared to people with more
      education years after adjustment for age and gender. Associations are significant
      in all welfare regimes, except for the Southern. CONCLUSION: Educational
      inequalities in the perception of need for seeking health care can be found in
      different welfare regimes.

PMID- 19763394
TI  - Aging and utilization of hospital services in Hong Kong: retrospective cohort
      study.
AB  - OBJECTIVES: We tested the hypotheses firstly that people dying in older age
      groups do not use hospital services more than those dying in younger age groups
      in the previous 3 years before death; secondly, that there may be compression of
      morbidity demonstrated by a decline in the use of hospital services among people
      in the last 3 years before death in the older age groups. METHODS: We extracted
      mortality data from all hospitals of the Hospital Authority and analyzed the data
      using negative binomial regression with duration of hospital stay before death as
      the outcome variables; age, gender, year of death (period), and birth cohort were
      predictor variables. RESULTS: People dying in older age groups do not use in
      patient hospital services more than younger age groups in the 3 years before
      death. However, they do use more AED services. No compression in morbidity was
      demonstrated. CONCLUSIONS: Data obtained from this retrospective study may be
      used to project future usage for each type of service as a result of changing age
      structure of the population.

PMID- 19763395
TI  - Not just angiotensinases: new roles for the angiotensin-converting enzymes.
AB  - The renin-angiotensin system (RAS) is a critical regulator of blood pressure and
      fluid homeostasis. Angiotensin II, the primary bioactive peptide of the RAS, is
      generated from angiotensin I by angiotensin-converting enzyme (ACE). A homologue
      of ACE, ACE2, is able to convert angiotensin II to a peptide with opposing
      effects, angiotensin-(1-7). It is proposed that disturbance of the balance of ACE
      and ACE2 expression and/or function is important in pathologies in which
      angiotensin II plays a role. These include cardiovascular and renal disease, lung
      injury and liver fibrosis. The critical roles of ACE and ACE2 in regulating
      angiotensin II levels have traditionally focussed attention on their activities
      as angiotensinases. Recent discoveries, however, have illuminated the roles of
      these enzymes and of the ACE2 homologue, collectrin, in intracellular trafficking
      and signalling. This paper reviews the key literature regarding both the
      catalytic and non-catalytic roles of the angiotensin-converting enzyme gene
      family.

PMID- 19763396
TI  - Suppressor of cytokine signaling-1 inhibits caspase activation  and protects from
      cytokine-induced beta cell death.
AB  - Pancreatic beta cell damage caused by proinflammatory cytokines interleukin-1beta
      (IL-1beta), interferon-gamma (IFNgamma) and tumor necrosis factor-alpha
      (TNFalpha) is a key event in the pathogenesis of type 1 diabetes. The suppressor
      of cytokine signaling-1 (SOCS-1) blocks IFNgamma-induced signaling and prevents
      diabetes in the non-obese diabetic mouse. Here, we investigated if SOCS-1
      overexpression in primary beta cells provides protection from cytokine-induced
      islet cell dysfunction and death. We demonstrate that SOCS-1 does not prevent
      increase in NO production and decrease in glucose-stimulated insulin secretion in
      the presence of IL-1beta, IFNgamma, TNFalpha. However, it decreases the
      activation of caspase-3, -8 and -9, and thereby, promotes a robust protection
      from cytokine-induced beta cell death. Our data suggest that SOCS-1
      overexpression may not be sufficient in preventing all the biological activities
      of IFNgamma in beta cells. In summary, we show that interference with IFNgamma
      signal transduction pathways by SOCS-1 inhibits cytokine-stimulated pancreatic
      beta cell death.

PMID- 19763397
TI  - Emerging concepts in acute mountain sickness and high-altitude cerebral edema:
      from the molecular to the morphological.
AB  - Acute mountain sickness (AMS) is a neurological disorder that typically affects
      mountaineers who ascend to high altitude. The symptoms have traditionally been
      ascribed to intracranial hypertension caused by extracellular vasogenic edematous
      brain swelling subsequent to mechanical disruption of the blood-brain barrier in
      hypoxia. However, recent diffusion-weighted magnetic resonance imaging studies
      have identified mild astrocytic swelling caused by a net redistribution of fluid
      from the "hypoxia-primed" extracellular space to the intracellular space without
      any evidence for further barrier disruption or additional increment in brain
      edema, swelling or pressure. These findings and the observation of minor
      vasogenic edema present in individuals with and without AMS suggest that the
      symptoms are not explained by cerebral edema. This has led to a re-evaluation of
      the relevant pathogenic events with a specific focus on free radicals and their
      interaction with the trigeminovascular system.

PMID- 19763398
TI  - Erythropoietin but not VEGF has a protective effect on auditory hair cells in the
      inner ear.
AB  - It has recently been shown that the oxygen-regulated factors erythropoietin (Epo)
      and vascular endothelial growth factor (VEGF) confer protection on different
      cells, including neuronal-derived ones. The receptors for Epo and VEGF are widely
      expressed in different organs. Since mammalian auditory hair cells can
      irreversibly be damaged by different agents, we aimed to identify otoprotective
      compounds. We focused on the role of Epo and VEGF in the inner ear and review the
      recent studies. Epo and its receptor are expressed in the inner ear. In vitro
      experiments on auditory hair cells showed a protective effect of Epo in ischemia-
      and gentamicin-induced hair cell damage. In contrast, an in vivo study using an
      animal model of noise-induced hearing loss showed a negative effect of Epo. Also
      VEGF and its receptors are expressed in the inner ear. Changes in the expression
      of VEGF or its receptors have been found in the cochlea after noise exposure,
      transcranial vibration and diabetic or aged animals. Until now, there are no
      studies about a direct effect of VEGF on auditory hair cells in vitro or in vivo.
      We could exclude a protective effect of VEGF on gentamicin-induced auditory hair
      cell damage in vitro. Thus, we conclude that Epo but not VEGF has a protective
      effect on auditory hair cell damage at least in vitro.

PMID- 19763401
TI  - [Oral hygiene in nursing home residents. Impact of an oral health education
      programme for the nursing personnel on the residents' oral health].
AB  - Many studies have shown urgent need in improving oral health hygiene in nursing
      home residents. Deficits in the knowledge of the personnel in dental and oral
      hygiene are often cited as one of the causes. Therefore in the spring of 2007 the
      nursing personnel of three nursing homes attended an oral health education
      programme. This programme was evaluated by examining the oral and dental health
      status of the residents, prior to and up to 12 months after the hygiene
      education. In three nursing homes in the Frankfurt am Main area, the oral health
      status of 113 residents was examined by a dentist with special education in
      geriatric dentistry, after receiving informed consent. Mean age was 80+/-9,2
      years (49-97 years, 91 women, 40 men). Before, and 4, 8, and 12 months after
      education of the caregivers, the following data were recorded in the residents:
      DMF-T index (decayed, missed, filled teeth), plaque index, sulcus bleeding index
      (SBI), denture hygiene index (DHI), coating of the tongue. Two-thirds of the
      residents were dependent on caregivers' support for dental care. Initially, in
      two-thirds of the residents, a high plaque index (PLI>2) and denture hygiene
      index (DHI>4) was found, in 90% of the residents SBI was > 50%, in 74% of them
      the tongue was partly or totally coated. In 45% of the residents restorative
      treatment was required. After the education programme for the personnel, good
      improvement in oral health of the residents could be stated, with 43% residents
      exhibiting PLI>2 and 77% showing SBI > 50%. The percentage of clean and well
      cared for dental prostheses had increased from ca. 30% up to 70%. Within the 4
      months 29 of 57 residents with recommendations for dental therapy had been seen
      by the dentist, 12 months after the first examination, dental therapy had to be
      recommended to only 19 residents. Education of the nursing staff in nursing homes
      is effective in improving oral health of the residents. Therefore, all
      residential homes will be offered regular and free education programmes in oral
      health for their personnel; this programme will be offered by the chamber of
      dentists in Hessen, Germany, and the public health services, Frankfurt/Main,
      Germany.

PMID- 19763400
TI  - A phase I study of zibotentan (ZD4054) in patients with metastatic, castrate
      resistant prostate cancer.
AB  - PURPOSE: To assess the maximum well-tolerated dose (MWTD), dose limiting toxicity
      (DLT), pharmacokinetics (PK) and pharmacodynamics of zibotentan, a novel specific
      endothelin-A receptor antagonist, in patients with metastatic prostate cancer.
      METHODS: Patients with metastatic, castrate-resistant prostate cancer (CRPC) were
      treated with escalating doses of oral zibotentan (ZD4054) 10-200 mg once daily.
      The initial cohort received 28 daily doses (Period 1). Patients who had evidence
      of clinical benefit and who had not met any of the criteria for withdrawal were
      allowed to receive zibotentan at their current dose level until they no longer
      derived clinical benefit (Period 2). PK of zibotentan and changes in prostate
      specific antigen and bone markers were also assessed. RESULTS: Sixteen patients
      were evaluable for the safety and single-dose PK analyses. Eleven patients
      completed Period 1, and nine patients proceeded to Period 2. DLTs were
      encountered at 22.5 mg; one patient had grade 3 dyspnea and peripheral edema and
      a second patient had grade 3 headache and intraventricular hemorrhage. Enrollment
      was expanded at the 15 mg dose level to further determine the safety and
      tolerability of zibotentan. No DLTs were seen at 15 mg, and the most frequent
      adverse events were headache, peripheral edema, fatigue, nasal congestion and
      nausea. CONCLUSIONS: The MWTD for zibotentan was 15 mg orally daily. The
      predominant adverse events observed were consistent with those reported for this
      class of drugs, and prolonged stable disease was noted in some patients. Phase
      III studies with zibotentan in men with metastatic CRPC are ongoing.

PMID- 19763399
TI  - Contribution of hypoxia to Alzheimer's disease: is HIF-1alpha a mediator of
      neurodegeneration?
AB  - The mammalian brain is extremely sensitive to alterations in cellular homeostasis
      as a result of environmental or physiological insults. In particular,
      hypoxic/ischemic challenges (i.e. reduced oxygen and/or glucose delivery) cause
      severe and detrimental alterations in brain function and can trigger neuronal
      cell death within minutes. Unfortunately, as we age, oxygen delivery to cells and
      tissues is impaired, thereby increasing the susceptibility of neurons to damage.
      Thus, hypoxic (neuronal) adaptation is significantly compromised during aging.
      Many neurological diseases, such as stroke, Alzheimer's disease (AD), Parkinson's
      disease and diabetes, are characterized by hypoxia, a state that is believed to
      only exacerbate disease progression. However, the contribution of hypoxia and
      hypoxia-mediated pathways to neurodegeneration remains unclear. This review
      discusses current evidence on the contribution of oxygen deprivation to AD, with
      an emphasis on hypoxia inducible transcription factor-1 (HIF-1)-mediated pathways
      and the association of AD with the cytoskeleton regulator cyclin-dependent kinase
      5.

PMID- 19763402
TI  - [University medicine in transition].

PMID- 19763403
TI  - [Personnel and organizational prerequisites for prevention and control of
      nosocomial infections].

PMID- 19763404
TI  - Aldosterone improves contractile function of adult rat ventricular cardiomyocytes
      in a non-acute way: potential relationship to the calcium paradox of
      aldosteronism.
AB  - Heart failure is accompanied by electrolyte disturbance including reduced calcium
      and sodium in the extracellular milieu but increased calcium within cells, a
      phenomenon called "calcium paradox". Aldosteronism is considered as part of this
      disorder. Aldosterone antagonism is known to reduce cardiac mortality on top of
      standard therapies such as antagonism of the renin-angiotensin-system. However,
      the effect of aldosterone on cardiac function under basal conditions and
      conditions more closely related to those seen in heart failure remains elusive.
      In order to address this question the function of isolated cardiomyocytes was
      determined as unloaded cell shortening. Cardiomyocytes were isolated from adult
      rat hearts and cultured for 24 h in the presence of aldosterone. Thereafter, cell
      shortening was determined in cells that were electrically paced (0.5-2.0 Hz). The
      effect of aldosterone on cell shortening was investigated under basal and maximal
      inotropic stimulation, preincubation with angiotensin II and myocytes from
      spontaneously hypertensive rats. The composition of the culture medium was
      modified according to the extracellular milieu found in patients with end-stage
      heart failure. Aldosterone increased cell shortening in a frequency-dependent way
      under basal conditions and conditions of low calcium. It potentiated the effect
      of beta-adrenoceptor stimulation, increased the formation of oxygen radicals, and
      increased diastolic and systolic calcium. In conclusion, chronic exposure to
      aldosterone improves the function of cardiomyocytes under basal conditions and
      electrolyte disturbances that mimic the situation found in heart failure
      patients.

PMID- 19763405
TI  - Heterologous Escherichia coli expression, purification and characterization of
      the GrmA aminoglycoside-resistance methyltransferase.
AB  - The mechanism of resistance to aminoglycosides based on methylation of their
      target, 16S rRNA, was until recently described only in antibiotic producing
      microorganisms. However, equivalent methyltransferases have now also been
      identified among numerous clinical Gram-negative pathogenic isolates. We have
      cloned, expressed, and purified GrmA, the aminoglycoside-resistance
      methyltransferase from Micromonospora purpurea, producer of gentamicin complex.
      Two vectors were created that express protein with an N-terminal 6x histidine tag
      with and without an enterokinase recognition producing proteins His(6)-EK-GrmA
      and His(6)-GrmA, respectively. The activity of both recombinant proteins was
      demonstrated in vivo. After optimized expression and native purification both
      protein variants proved to be active in in vitro methylation assays. This work
      lays a foundation for future detailed biochemical, structural and pharmacological
      studies with this member of an important group of aminoglycoside-resistance
      enzymes.

PMID- 19763406
TI  - Residue Tyr224 is critical for the thermostability of Geobacillus sp. RD-2
      lipase.
AB  - A thermophilic lipase (lipGRD) from Geobacillus sp. RD-2, isolated from a hot
      spring in Yunnan, China, was cloned and over-expressed in Escherichia coli. The
      function of the conserved residue, Tyr224, near the presumed temperature switch
      site was analyzed by site-directed saturation mutagenesis. The activity of the
      wild type lipGRD was optimal at 55 degrees C and pH 7.5, but that from mutant
      Y224C was optimally active at 35 degrees C, whereas Y224P lipase was optimally
      active at 65 degrees C. Furthermore, the latter lipase retained 60% of its
      activity after incubation at 65 degrees C for 5 h. The conserved residue Tyr224,
      which is close to the lid helix, is the key amino acid residue determining the
      thermostability of the thermostable lipase.

PMID- 19763407
TI  - Low serum magnesium levels in elderly subjects with metabolic syndrome.
AB  - This study aims at determining possible association between serum magnesium (Mg)
      concentrations and metabolic syndrome (MetS) in elderly subjects. Subjects were
      137 men and women aged 60 to 90 years, selected from among participants of the
      Tehran Lipid and Glucose Study after excluding those taking medications for
      hypertension and dyslipidemia. Serum Mg levels were measured by atomic absorption
      spectrometry and MetS was defined according to ATP III criteria. The overall
      prevalence of MetS was 43.8%. Among MetS components, only plasma glucose showed a
      negative correlation with serum Mg concentrations (r = -0.194, p = 0.024).
      Subjects with MetS had significantly lower serum Mg concentrations compared with
      non-MetS ones (2.09 +/- 0.03 vs. 2.18 +/- 0.03 mg/dL, p = 0.033) even after
      adjustments with MetS components except for hyperglycemia (2.04 +/- 0.06 vs. 2.20
      +/- 0.05 mg/dL, p = 0.011). However, after adjustment for hyperglycemia per se or
      along with the other MetS components, the significant difference between serum Mg
      levels in subjects with and without MetS disappeared. In conclusion, serum Mg
      level is diminished in elderly subjects with MetS, and hyperglycemia may play
      dominant role in this decrease; however, the results do not clarify whether the
      low serum Mg level is a consequence of hyperglycemia or is a risk factor
      contributing to its development.

PMID- 19763408
TI  - Selenium and vitamin E modulates radiation-induced liver toxicity in pregnant and
      nonpregnant rat: effects of colemanite and hematite shielding.
AB  - The levels of liver lipid peroxidation, glutathione peroxidase, reduced
      glutathione, and vitamins A and E were used to follow the level of oxidative
      damage caused by ionizing radiation in pregnant rats. The possible protective
      effects of selenium and vitamin E supplemented to rats housed in concrete
      protected cages using hematite and colemanite were tested and compared to
      untreated controls. Ninety-six rats were randomly divided into four main equal
      groups namely control (A), normal concrete (B), concrete containing colemanite
      (C), and concrete containing hematite (D). Except group A, all groups exposed to
      7 Gy radiation. The four main groups were divided into four subgroups each as
      follows: subgroups 1 (n = 6): nonpregnant control rats. Subgroups 2 (n = 6):
      selenium and vitamin E combination was intraperitoneally (i.p.) given to the
      nonpregnant rats for 20 days. Subgroups 3 (n = 6): pregnant control rats.
      Subgroups 4 (n = 6): selenium and vitamin E combination was i.p. given to the
      pregnant rats for concessive 20 days. Lactate dehydrogenate, alkaline phosphates,
      and lipid peroxidation values were higher in subgroups 1 and 3 than in no
      radiation group although glutathione peroxidase and vitamin E levels in liver
      were lower in radiation group than in no radiation group. Lactate dehydrogenate
      activity and lipid peroxidation levels were found to be decreased in subgroups 2
      and 4 protected with concrete containing hematite and colemanite when compared to
      subgroup 1 and 3 with normal concrete. The radiation doses in rats housed by
      concrete without colemanite and hematite exposed radiation clearly showed liver
      degeneration. In conclusion, selenium and vitamin E supplementations and housing
      by concrete with colemanite was found to offer protection against gamma
      irradiation-induced liver damage and oxidative stress in rats, probably by
      exerting a protective effect against liver necrosis via its free radical
      scavenging and membrane stabilizing. Protective effects of colemanite in the
      liver seem to be more important than in hematite.

PMID- 19763409
TI  - Comparison of the bacterial community and characterization of plant growth
      promoting rhizobacteria from different genotypes of Chrysopogon zizanioides (L.)
      Roberty (vetiver) rhizospheres.
AB  - Molecular approaches [PCR-denaturing gradient gel electrophoresis (DGGE)] were
      used to determine whether three different vetiver (Chrysopogon zizanioides)
      genotypes, commercially used in Brazil and considered economically important over
      the world, select specific bacterial populations to coexist in their
      rhizospheres. DGGE profiles revealed that the predominant rhizospheric bacterial
      community hardly varies regarding the vetiver genotype. Moreover, using
      traditional cultivation methods, bacterial strains were isolated from the
      different rhizospheres. Colonies presenting different morphologies (83) were
      selected for determining their potential for plant growth promotion. More than
      half of the strains tested (57.8%) were amplified by PCR using nifH-based
      primers, specific for the enzyme nitrogenase reductase. The production of
      siderophores was observed in 88% of the strains, while the production of
      antimicrobial substances was detected in only 14.5% of the isolates when
      Micrococcus sp. was used as the indicator strain. Production of indole-3-acetic
      acid and the solubilization of phosphate were observed in 55.4% and 59% of the
      isolates, respectively. In total, 44 strains (53%) presented at least three
      characteristics of plant growth promotion and were submitted to amplified
      ribosomal DNA restriction analysis. Twenty-four genetic groups were formed at
      100% similarity and one representative of each group was selected for their
      identification by partial 16S rRNA gene sequencing. They were affiliated with the
      genera Acinetobacter, Comamonas, Chryseobacterium, Klebsiella, Enterobacter,
      Pantoea, Dyella, Burkholderia, or Pseudomonas. These strains can be considered of
      great importance as possible biofertilizers in vetiver.

PMID- 19763411
TI  - Evaluation of antagonistic activities of Bacillus subtilis and Bacillus
      licheniformis against wood-staining fungi: in vitro and in vivo experiments.
AB  - The antifungal activity of bacterial strains Bacillus subtilis EF 617317 and B.
      licheniformis EF 617325 was demonstrated against sapstaining fungal cultures
      Ophiostoma flexuosum, O. tetropii, O. polonicum, and O. ips in both in vitro and
      in vivo conditions. The crude active supernatant fractions of 7 days old B.
      subtilis and B. licheniformis cultures inhibited the growth of sapstaining fungi
      in laboratory experiments. Thermostability and pH stability of crude supernatants
      were determined by series of experiments. FT-IR analysis was performed to confirm
      the surface structural groups of lipoproteins present in the crude active
      supernatant. Partial purification of lipopeptides present in the crude
      supernatant was done by using Cellulose anion exchange chromatography and
      followed by Sephadex gel filtration chromatography. Partially purified compounds
      significantly inhibited the sapstaining fungal growth by in vitro analysis. The
      lipopeptides responsible for antifungal activity were identified by electrospray
      ionization mass spectrometry after partial purification by ion exchange and gel
      filtration chromatography. Four major ion peaks were identified as m/z 1023,
      1038, 1060, and 1081 in B. licheniformis and 3 major ion peaks were identified as
      m/z 1036, 1058, and 1090 in B. subtilis. In conclusion, the partially purified
      lipopeptides may belong to surfactin and iturin family. In vivo analysis for
      antifungal activity of lipopeptides on wood was conducted in laboratory. In
      addition, the potential of extracts for fungal inhibition on surface and internal
      part of wood samples were analyzed by scanning electron microscopy.

PMID- 19763410
TI  - Molecular analysis of prokaryotic diversity in the deep subsurface of the former
      Homestake gold mine, South Dakota, USA.
AB  - A culture-independent molecular phylogenetic analysis was carried out to study
      the prokaryotic diversity in two soil samples collected from the subsurface (1.34
      km depth) of the former Homestake gold mine, Lead, South Dakota, USA at two
      sites, the Ross shaft and number 6 Winze. Microbial community analyses were
      performed by cloning and sequencing of 16S rRNA genes retrieved directly from
      soil samples. Geochemical characterization of soils revealed high amount of toxic
      metals such as As, Cd, Co, Cr, Cu, Ni, Pb, Zn, and U at both the sites.
      Phylogenetic analyses showed that soil samples were predominantly composed of
      phylotypes related to phylum Proteobacteria. Other phyla detected in libraries
      were Acidobacteria, Actinobacteria, Bacteroidetes, Chloroflexi, Chlorobi,
      Firmicutes, Gemmatimonadetes, Nitrospirae, Planctomycetes, Verrucomicrobia, and
      candidate divisions OP10 and TM7. The majority (>95%) of the phylotypes retrieved
      in the libraries were most closely related to environmental sequences from yet
      uncultured bacteria representing a hitherto unidentified diversity. The archaeal
      communities at both the sites exhibited lower diversity and were most closely
      affiliated to uncultivated species within the Crenarchaeota. Results showed the
      existence of diverse microbial populations in deep subsurface environment of the
      Homestake gold mine. Statistical analyses demonstrated that each site harbored
      phylogenetically distinct microbial populations that were more diverse at Ross
      site compare to winze site.

PMID- 19763412
TI  - Endophytic bacterial diversity in grapevine (Vitis vinifera L.) leaves described
      by 16S rRNA gene sequence analysis and length heterogeneity-PCR.
AB  - Diversity of bacterial endophytes associated with grapevine leaf tissues was
      analyzed by cultivation and cultivation-independent methods. In order to identify
      bacterial endophytes directly from metagenome, a protocol for bacteria enrichment
      and DNA extraction was optimized. Sequence analysis of 16S rRNA gene libraries
      underscored five diverse Operational Taxonomic Units (OTUs), showing best
      sequence matches with gamma-Proteobacteria, family Enterobacteriaceae, with a
      dominance of the genus Pantoea. Bacteria isolation through cultivation revealed
      the presence of six OTUs, showing best sequence matches with Actinobacteria,
      genus Curtobacterium, and with Firmicutes genera Bacillus and Enterococcus.
      Length Heterogeneity-PCR (LH-PCR) electrophoretic peaks from single bacterial
      clones were used to setup a database representing the bacterial endophytes
      identified in association with grapevine tissues. Analysis of healthy and
      phytoplasma-infected grapevine plants showed that LH-PCR could be a useful
      complementary tool for examining the diversity of bacterial endophytes especially
      for diversity survey on a large number of samples.

PMID- 19763413
TI  - Identification and characterization of metagenomic fragments from tidal flat
      sediment.
AB  - Phylogenetic surveys based on cultivation-independent methods have revealed that
      tidal flat sediments are environments with extensive microbial diversity. Since
      most of prokaryotes in nature cannot be easily cultivated under general
      laboratory conditions, our knowledge on prokaryotic dwellers in tidal flat
      sediment is mainly based on the analysis of metagenomes. Microbial community
      analysis based on the 16S rRNA gene and other phylogenetic markers has been
      widely used to provide important information on the role of microorganisms, but
      it is basically an indirect means, compared with direct sequencing of metagenomic
      DNAs. In this study, we applied a sequence-based metagenomic approach to
      characterize uncultivated prokaryotes from tidal flat sediment. Two large-insert
      genomic libraries based on fosmid were constructed from tidal flat metagenomic
      DNA. A survey based on end-sequencing of selected fosmid clones resulted in the
      identification of clones containing 274 bacterial and 16 archaeal homologs in
      which majority were of proteobacterial origins. Two fosmid clones containing
      large metagenomic DNAs were completely sequenced using the shotgun method. Both
      DNA inserts contained more than 20 genes encoding putative proteins which implied
      their ecological roles in tidal flat sediment. Phylogenetic analyses of
      evolutionary conserved proteins indicate that these clones are not closely
      related to known prokaryotes whose genome sequence is known, and genes in tidal
      flat may be subjected to extensive lateral gene transfer, notably between domains
      Bacteria and Archaea. This is the first report demonstrating that direct
      sequencing of metagenomic gene library is useful in underpinning the genetic
      makeup and functional roles of prokaryotes in tidal flat sediments.

PMID- 19763414
TI  - Impact of some environmental factors on growth and production of ochratoxin A
      of/by Aspergillus tubingensis, A. niger, and A. carbonarius isolated from
      Moroccan grapes.
AB  - The effects of temperature, water activity (aw), incubation time, and their
      combinations on radial growth and ochratoxin A (OTA) production of/by eight
      Aspergillus niger aggregate strains (six A. tubingensis and two A. niger) and
      four A. carbonarius isolated from Moroccan grapes were studied. Optimal
      conditions for the growth of most studied strains were shown to be at 25 degrees
      C and 0.95 aw. No growth was observed at 10 degrees C regardless of the water
      activity and isolates. The optimal temperature for OTA production was in the
      range of 25 degrees C-30 degrees C for A. carbonarius and 30 degrees C-37 degrees
      C for A. niger aggregate. The optimal aw for toxin production was 0.95-0.99 for
      A. carbonarius and 0.90-0.95 for A. niger aggregate. Mean OTA concentration
      produced by all the isolates of A. niger aggregate tested at all sampling times
      shows that maximum amount of OTA (0.24 microg/g) was produced at 37 degrees C and
      0.90 aw. However, for A. carbonarius, mean maximum amounts of OTA (0.22 microg/g)
      were observed at 25 degrees C and 0.99 aw. Analysis of variance showed that the
      effects of all single factors (aw, isolate, temperature and incubation time) and
      their interactions on growth and OTA production were highly significant.

PMID- 19763415
TI  - Effect of fungal pellet morphology on enzyme activities involved in phthalate
      degradation.
AB  - Pellet size of white rot fungus, Pleurotus ostreatus may affect the secretion of
      its degradative enzymes and accompanying biodegrading capability, but could be
      controlled by several physical culture conditions in liquid culture. The pellet
      size of P. ostreatus was affected by the volume of inoculum, flask, and medium,
      but the agitation speed was the most important control factor. At the lower
      agitation speed of 100 rpm, the large pellets were formed and the laccase
      activity was higher than that of small pelleted culture at 150 rpm, which might
      be due to loose intrapellet structure. However, the biodegradation rates of
      benzylbutylphthalate and dimethylphthalate were higher in the small pelleted
      culture, which indicated the involvement of other degradative enzyme rather than
      laccase. The activity of esterase which catalyzes the nonphenolic compounds
      before the reaction of ligninolytic enzymes was higher in the small pelleted
      culture, and coincided with the degradation pattern of phthalates. This study
      suggests the optimization of pellet morphology and subsequent secretion of
      degradative enzymes is necessary for the efficient removal of recalcitrants by
      white rot fungi.

PMID- 19763416
TI  - Chrysosporium pseudomerdarium produces gibberellins and promotes plant growth.
AB  - We isolated 10 endophytic fungi from the roots of drought stressed soybean
      cultivar Hwangkeumkong and bioassayed on waito-c rice and soybean seedlings, in
      order to identify plant growth-promoting fungi. The fungal isolate D-2-1 provided
      the best result for plant height and biomass promotion as compared to wild type
      Gibberella fujikuroi. The D-2-1 culture filtrate (CF) was analyzed for the
      presence of gibberellins (GAs) and it was observed that all physiologically
      active GAs, especially gibberellic acid, were present in higher amounts (GA1,
      0.24 ng/ml; GA3, 8.99 ng/ml; GA4, 2.58 ng/ml and GA7, 1.39 ng/ml) in conjunction
      with physiologically inactive GA5, GA9, GA15, GA19, and GA24. The fungal isolate
      D-2-1 was identified as a new strain of Chrysosporium pseudomerdarium through
      phylogenetic analysis of 18S rDNA sequence. Plant growth promotion and GAs
      production capacity of genus Chrysosporium have been reported for the first time
      in this study.

PMID- 19763417
TI  - Identification and characterization of a class III chitin synthase gene of
      Moniliophthora perniciosa, the fungus that causes witches' broom disease of
      cacao.
AB  - Chitin synthase (CHS) is a glucosyltransferase that converts UDP-N
      acetylglucosamine into chitin, one of the main components of fungal cell wall.
      Class III chitin synthases act directly in the formation of the cell wall. They
      catalyze the conversion of the immediate precursor of chitin and are responsible
      for the majority of chitin synthesis in fungi. As such, they are highly specific
      molecular targets for drugs that can inhibit the growth and development of fungal
      pathogens. In this work, we have identified and characterized a chitin synthase
      gene of Moniliophthora perniciosa (Mopchs) by primer walking. The complete gene
      sequence is 3,443 bp, interrupted by 13 small introns, and comprises a cDNA with
      an ORF with 2,739 bp, whose terminal region was experimentally determined,
      encoding a protein with 913 aa that harbors all the motifs and domains typically
      found in class III chitin synthases. This is the first report on the
      characterization of a chitin synthase gene, its mature transcription product, and
      its putative protein in basidioma and secondary mycelium stages of M. perniciosa,
      a basidiomycotan fungus that causes witches' broom disease of cacao.

PMID- 19763418
TI  - Molecular diversity of chrysoviruses in Korean isolates of a new fungal species,
      Cryphonectria nitschkei.
AB  - Genetic diversity of the chrysovirus within the four fungal strains was analyzed
      by comparing the full-length sequences of cloned chrysoviral genes encoding the
      RNA-dependent RNA polymerase (RdRp) and capsid protein (CP). Because the
      morphological characteristics of four chrysovirus-infected Cryphonectria spp.
      strains were different, strain identification was conducted via sequence
      comparison of the internal transcribed spacers (ITSs) of the fungal rRNA gene.
      Phylogenic analysis of the ITS regions revealed that the four strains were
      closely clustered with the reference strain of Cryphonectria nitschkei, while
      they were more distantly related to other common Cryphonectria species,
      indicating that they were likely C. nitschkei. Sequence comparison among
      chrysoviruses from Korean C. nitschkei strains revealed that similarities of the
      RdRp and CP genes ranged from 98% to 100% and from 95% to 100%, respectively, at
      the protein level. Their corresponding nucleotide sequences showed 97% to 100%
      and 84% to 100% identities, respectively. Compared to RdRp, the CP gene had more
      divergence, suggesting the presence of genes possessing different evolutionary
      rates within the chrysovirus genome. Sequence comparisons with other known
      chrysoviruses showed that the four Korean chrysoviruses were clustered together
      at the next lineage level. Discovering why two strains (bsl31 and bsl32)
      containing identical ITS sequences and chrysoviruses display different phenotypes
      should prove interesting.

PMID- 19763419
TI  - Transmission of Methylobacterium mesophilicum by Bucephalogonia xanthophis for
      paratransgenic control strategy of citrus variegated chlorosis.
AB  - Methylobacterium mesophilicum, originally isolated as an endophytic bacterium
      from citrus plants, was genetically transformed to express green fluorescent
      protein (GFP). The GFP-labeled strain of M. mesophilicum was inoculated into
      Catharanthus roseus (model plant) seedlings and further observed colonizing its
      xylem vessels. The transmission of this endophyte by Bucephalogonia xanthophis,
      one of the insect vectors that transmit Xylella fastidiosa subsp. pauca, was
      verified by insects feeding from fluids containing the GFP bacterium followed by
      transmission to plants and isolating the endophyte from C. roseus plants. Forty
      five days after inoculation, the plants exhibited endophytic colonization by M.
      mesophilicum, confirming this bacterium as a nonpathogenic, xylem-associated
      endophyte. Our data demonstrate that M. mesophilicum not only occupy the same
      niche of X. fastidiosa subsp. pauca inside plants but also may be transmitted by
      B. xanthophis. The transmission, colonization, and genetic manipulation of M.
      mesophilicum is a prerequisite to examining the potential use of symbiotic
      control to interrupt the transmission of X. fastidiosa subsp. pauca, the
      bacterial pathogen causing Citrus variegated chlorosis by insect vectors.

PMID- 19763420
TI  - Gene expression profile of Helicobacter pylori in response to growth temperature
      variation.
AB  - A Helicobacter pylori whole-genome DNA microarray was constructed to study
      expression profiles of H. pylori in response to a sudden temperature transfer
      from 37 degrees C to 20 degrees C. The expression level of the genome at each of
      four time points (15, 30, 60, and 120 min) after temperature downshift was
      compared with that just before cold treatment. Globally, 10.2 % (n=167) of the
      total predicted H. pylori genes (n=1636) represented on the microarray were
      significantly differentially expressed (p<0.05) over a 120 min period after shift
      to low temperature. The expression profiles of the differentially expressed genes
      were grouped, and their expression patterns were validated by quantitative real
      time PCR. Up-regulated genes mainly included genes involved in energy metabolism
      and substance metabolism, cellular processes, protein fate, ribosomal protein
      genes, and hypothetical protein genes, which indicate the compensational
      responses of H. pylori to temperature downshift. Those genes play important roles
      in adaption to temperature downshift of H. pylori. Down-regulation of DNA
      metabolism genes and cell envelope genes and cellular processes genes may reflect
      damaged functions under low temperature, which is unfavorable to bacterial
      infection and propagation. Overall, this time-course study provides new insights
      into the primary response of H. pylori to a sudden temperature downshift, which
      allow the bacteria to survive and adapt to the new host environment.

PMID- 19763421
TI  - Cloning and molecular characterization of a novel rolling-circle replicating
      plasmid, pK1S-1, from Bacillus thuringiensis subsp. kurstaki K1.
AB  - Bacillus thuringiensis, an entomopathogenic bacterium belonging to the B. cereus
      group, harbors numerous extra-chromosomal DNA molecules whose sizes range from 2
      to 250 kb. In this study, we used a plasmid capture system (PCS) to clone three
      small plasmids from B. thuringiensis subsp. kurstaki Kl which were not found in
      B. thuringiensis subsp. kurstaki HD-1, and determined the complete nucleotide
      sequence of plasmid pKlS-1 (5.5 kb). Of the six putative open reading frames
      (ORF2-ORF7) in pKlS-1, ORF2 (MobKl) showed approximately 90% aa identity with the
      Mob-proteins of pGI2 and pTX14-2, which are rolling circle replicating group VII
      (RCR group VII) plasmids from B. thuringiensis. In addition, a putative origin of
      transfer (oriT) showed 95.8% identity with those of pGI2 and pTX14-2. ORF3
      (RepK1) showed relatively low aa identity (17.8-25.2%) with the Rep protein coded
      by RCR plasmids, however. The putative double-strand origin of replication (dso)
      and single-strand origin of replication (sso) of pKlS-1 exhibited approximately
      70% and 64% identities with those of pGI2 and pTX14-2. ORF6 and 7 showed greater
      than 50% similarities with alkaline serine protease, which belongs to the
      subtilase family. The other 2 ORFs were identified as hypothetical proteins. To
      determine the replicon of pKlS-1, seven subclones were contructed in the B.
      thuringiensis ori-negative pHTIK vector and were electroporated into a plasmid
      cured B. thuringiensis strain. The 1.6 kb region that included the putative ORF3
      (ReplK), dso and ORF4, exhibited replication ability. These findings identified
      pKlS-1 as a new RCR group VII plasmid, and determined its replication region.

PMID- 19763422
TI  - Identification and characterization of acetyl-CoA carboxylase gene cluster in
      Streptomyces toxytricini.
AB  - The gene locus for acetyl-CoA carboxylase (ACC) involved in the primary
      metabolism was identified from the genomic library of Streptomyces toxytricini
      which produces a lipase inhibitor lipstatin. The 7.4 kb cloned gene was comprised
      of 5 ORFs including accD1, accA1, hmgL, fadST1, and stsF. In order to confirm the
      biochemical characteristics of AccA1, the gene was overexpressed in Escherichia
      coli cells, and the recombinant protein was purified through Ni2+ affinity
      chromatography. Because most of the expressed AccAl was biotinylated by host E.
      coli BirA in the presence of D-biotin, the non-biotinylated apo-AccA1 was
      purified after gene induction without D-biotin, followed by exclusion of holo
      AccA1 using streptavidin beads. The separated apo-AccA1 was post-translationally
      biotinylated by S. toxytricini biotin apo-protein ligase (BPL) in a time- and
      enzyme-dependent manner. This result supports that this gene cluster of S.
      toxytricini encodes the functional ACC enzyme subunits to be biotinylated.

PMID- 19763423
TI  - Effect of iron on cytolysin A expression in Salmonella enterica serovar Typhi.
AB  - Previously, a novel protein ClyA (Cytolysin A) has been identified in Escherichia
      coli K-12, Salmonella enterica serovars Typhi and Paratyphi A and Shigella.
      Salmonella spp. synthesize substantial amounts of ClyA upon infection of the
      human host, although the mechanism by which ClyA is induced in vivo is unclear.
      Since environmental signals could control the expression of virulence
      determinants, ClyA expression in S. Typhi Ty2 was tested by Western blotting in
      the presence of normal pooled human serum (NPS). The level of ClyA expression
      increased in the presence of NPS in a concentration-dependent manner. RPMI 1640
      medium similarly induced ClyA expression. ClyA expression was inversely
      proportional to the concentration of iron in RPMI medium. Therefore, we
      speculated that iron inhibited the expression of ClyA in S. Typhi Ty2, and free
      iron depletion may be one of the causes of S. Typhi-mediated induction of ClyA in
      vivo. Transcription from a clyA-lacZ fusion gene decreased as iron concentration
      increased, but not as significantly as the ClyA protein expression. It is
      concluded that the regulatory effect of iron on clyA expression is mainly at
      translational level.

PMID- 19763424
TI  - Helicobacter pylori proteins response to nitric oxide stress.
AB  - Helicobacter pylori is a highly pathogenic microorganism with various strategies
      to evade human immune responses. Nitric oxide (NO) and reactive nitrogen species
      (RNS) generated via nitric oxide synthase pathway are important effectors during
      the innate immune response. However, the mechanisms of H. pylori to survive the
      nitrosative stress are not clear. Here the proteomic approach has been used to
      define the adaptive response of H. pylori to nitrosative stress. Proteomic
      analysis showed that 38 protein spots were regulated by NO donor, sodium
      nitroprusside (SNP). These proteins were involved in protein processing, anti
      oxidation, general stress response, and virulence, as well as some unknown
      functions. Particularly, some of them were participated in iron metabolism,
      potentially under the control of ferric uptake regulator (Fur). Real time PCR
      revealed that fur was induced under nitrosative stress, consistent with our
      deduction. One stress-related protein up-regulated under nitrosative conditions
      was thioredoxin reductase (TrxR). Inactivation of fur or trxR can lead to
      increased susceptivity to nitrosative stress respectively. These studies
      described the adaptive response of H. pylori to nitric oxide stress, and analyzed
      the relevant role of Fur regulon and TrxR in nitrosative stress management.

PMID- 19763425
TI  - Genotypic characteristics of Haemophilus influenzae isolates from pediatric
      pneumonia patients in Chengdu city, Sichuan, China.
AB  - Two hundred and seventy-three Haemophilus influenzae strains isolated from
      pediatric pneumonia patients in China were studied. We used Multilocus Sequence
      Typing (MLST) to analyze genotypic characteristics. All strains were biotyped and
      serotyped. Relatedness and patterns of genes among isolates were determined by
      the analysis of MLST and eBURST. H. influenzae primarily causes acute pneumonia
      in children under 1 year old. Nontypeable H. influenzae was responsible for most
      cases of pediatric pneumonia. All 273 strains were classified into eight
      biotypes. They mostly belonged to the I, II, and III biotypes (17.6%, 43.6%, and
      22.7%, respectively). 62 strains (22.7%) produced beta-lactamase. We found 28
      novel alleles. Fifty different STs were found by MLST, of which 39 were novel.
      These were ST477 through ST508 and ST521 through ST527. Group 17 and predicted
      founders 503 were new groups in this study. No STs correlated with strains from
      Korea, which is adjacent to China. The H. influenzae strains from China appeared
      to have heterogeneous ST types patterns which may be the reason no outbreaks or
      epidemics of H. influenzae infections have occurred in Chengdu city, Sichuan,
      China.

PMID- 19763426
TI  - Fusion expression and immunogenicity of EHEC EspA-Stx2Al protein: implications
      for the vaccine development.
AB  - Shiga toxin 2 (Stx2) is a major virulence factor for enterohemorrhagic
      Escherichia coli (EHEC), which is encoded by lambda lysogenic phage integrated
      into EHEC chromosome. Stx2Al, Al subunit of Stx2 toxin has gathered extensive
      concerns due to its potential of being developed into a vaccine candidate.
      However, the substantial progress is hampered in part for the lack of a suitable
      in vitro expression system. Here we report use of the prokaryotic system pET
      28a::espA-Stx2Al/BL21 to carry out the fusion expression of Stx2Al which is
      linked to E. coli secreted protein A (EspA) at its N-terminus. Under the IPTG
      induction, EspA-Stx2Al fusion protein in the form of inclusion body was obtained
      successfully, whose expression level can reach about 40% of total bacterial
      protein at 25 degrees C, much higher than that at 37 degrees C. Western blot test
      suggested the refolded fusion protein is of excellent immuno-reactivity with both
      monoclonal antibodies, which are specific to EspA and Stx2Al, respectively. Anti
      sera from Balb/c mice immunized with the EspA-Stx2Al fusion protein were found to
      exhibit strong neutralization activity and protection capability in vitro and in
      vivo. These data have provided a novel feasible method to produce Stx2Al in large
      scale in vitro, which is implicated for the development of multivalent subunit
      vaccines candidate against EHEC 0157:H7 infections.

PMID- 19763427
TI  - Identification of a novel Streptomyces chattanoogensis L10 and enhancing its
      natamycin production by overexpressing positive regulator ScnRII.
AB  - A novel Streptomyces strain, L10, which is capable of producing natamycin, was
      isolated from a soil sample collected from Zhejiang province, China. On the basis
      of phylogenetic analysis of rpoB gene and 16S rDNA sequences, as well as
      phenotypic comparison, strain L10 (CGMCC 2644) is proposed to be a previously
      uncharacterized strain of S. chattanoogensis. By screening a cosmid library of
      strain L10 and primer walking, a partial sequence of scnRI and the entire
      sequence of scnRII were obtained, which are orthologues to the pathway-specific
      positive regulator genes of natamycin biosynthesis in S. natalensis. The
      engineered S. chattanoogensis Dl, generated by inserting an additional copy of
      scnRII into the chromosome of strain L10, increased its natamycin production by
      3.3 fold in YSG medium and 4.6 fold in YEME medium without sucrose.

PMID- 19763428
TI  - Nomenclature of ISCRl elements capable of mobilizing antibiotic resistance genes
      present in complex class 1 integrons.
AB  - The dissemination of many antibiotic resistance genes has arisen among members of
      the family Enterobacteriaceae. The dissemination mechanism of these antibiotic
      resistance genes is closely linked with insertion sequence common region 1
      (ISCRl). Thus, caution must be taken in clinical settings to prevent further
      dissemination of these antibiotic resistance genes. A nomenclature system of
      ISCRl variants, important for the antibiotic resistance dissemination, was
      proposed. The proposed system can designate all ISCRl variants on the basis of
      the detection time and by considering amino-acid substitution(s) compared with
      ISCRla. This nomenclature system of ISCRl variants can be applied to 19 groups
      (ISCRl to ISCR19) of the ISCR family and help some researchers to correctly
      designate new ISCR subgroups.

PMID- 19763429
TI  - Chemoprevention of ovarian cancer.

PMID- 19763430
TI  - Staging and surgical treatment.

PMID- 19763431
TI  - Novel therapeutic targets.

PMID- 19763432
TI  - Biomarker targets and novel therapeutics.

PMID- 19763433
TI  - Tumor suppressor genes.

PMID- 19763434
TI  - Epigenetics and ovarian cancer.

PMID- 19763435
TI  - Aberrant epithelial differentiation in ovarian cancer.

PMID- 19763436
TI  - The human kallikrein gene family: new biomarkers for ovarian cancer.

PMID- 19763437
TI  - Soluble epidermal growth factor receptor: a biomarker of epithelial ovarian
      cancer.

PMID- 19763439
TI  - Ras-superfamily GTP-ases in ovarian cancer.

PMID- 19763440
TI  - Lipid generation and signaling in ovarian cancer.

PMID- 19763441
TI  - Lysophosphatidic acid and invasion.

PMID- 19763438
TI  - Activated epidermal growth factor receptor in ovarian cancer.

PMID- 19763442
TI  - Cell adhesion in ovarian cancer.

PMID- 19763443
TI  - Microenvironmental regulation of ovarian cancer metastasis.

PMID- 19763445
TI  - Animal models of ovarian cancer.

PMID- 19763444
TI  - Organotypic models of metastasis: A three-dimensional culture mimicking the human
      peritoneum and omentum for the study of the early steps of ovarian cancer
      metastasis.

PMID- 19763446
TI  - Documentation and correlation of senologic findings.

PMID- 19763447
TI  - Comparison of large-core vacuum-assisted breast biopsy and excision systems.

PMID- 19763448
TI  - Sonographically guided vacuum-assisted breast biopsy using handheld mammotome.

PMID- 19763449
TI  - The vacora biopsy system.

PMID- 19763450
TI  - Available stereotactic systems for breast biopsy.

PMID- 19763451
TI  - MRI-guided minimally invasive breast procedures.

PMID- 19763452
TI  - Ductoscopy of intraductal neoplasia of the breast.

PMID- 19763453
TI  - Pathology of breast tissue obtained in minimally invasive biopsy procedures.

PMID- 19763454
TI  - Limitations of minimally invasive breast biopsy.

PMID- 19763455
TI  - Advances in breast imaging: a dilemma or progress?

PMID- 19763456
TI  - Cost-benefit analyses.

PMID- 19763457
TI  - Systematic Review and Meta-analysis of Recent Data.

PMID- 19763458
TI  - Microfabrication techniques for biologists: a primer on building micromachines.
AB  - In this chapter we review the fundamental techniques and processes underlying the
      fabrication of devices on the micron scale (referred to as "microfabrication").
      Principles laid down in the 1950s now form the basis of the semiconductor
      manufacturing industry; these principles are easily adaptable to the production
      of devices for biotechnological processing and analysis.

PMID- 19763459
TI  - The application of microfluidics in biology.
AB  - Recent advances in the bio- and nanotechnologies have led to the development of
      novel microsystems for bio-particle separation and analysis. Microsystems are
      already revolutionising the way we do science and have led to the development of
      a number of ultrasensitive bioanalytical devices capable of analysing complex
      biological samples. These devices have application in a number of diverse areas
      such as pollution monitoring, clinical diagnostics, drug discovery and biohazard
      detection. In this chapter we give an overview of the physical principles
      governing the behaviour of fluids and particles at the micron scale, which are
      relevant to the operation of microfluidic devices. We briefly discuss some of the
      fabrication technologies used in the production of microfluidic systems and then
      present a number of examples of devices and applications relevant to the
      biological and life sciences.

PMID- 19763460
TI  - Rapid prototyping of microstructures by soft lithography for biotechnology.
AB  - This chapter describes the methods and specific procedures used to fabricate
      microstructures by soft lithography. These techniques are useful for the
      prototyping of devices useful for applications in biotechnology. Fabrication by
      soft lithography does not require specialized or expensive equipment; the
      materials and facilities necessary are found commonly in biological and chemical
      laboratories in both academia and industry. The combination of the fact that the
      materials are low-cost and that the time from design to prototype device can be
      short (< 24 h) makes it possible to use and to screen rapidly devices that also
      can be disposable. Here we describe the procedures for fabricating
      microstructures with lateral dimensions as small as 1 mum. These types of
      microstructures are useful for microfluidic devices, cell-based assays, and
      bioengineered surfaces.

PMID- 19763461
TI  - Chemical synthesis in microreactors.
AB  - To develop a new generation of drugs, pharmaceutical companies need to be able to
      synthesise and screen novel chemicals with enhanced speed. New technology that
      would enable a cost neutral step change in the number of potential drug
      candidates would provide a distinct competitive advantage. Indeed the
      miniaturisation of chemical reactors offers many fundamental and practical
      advantages of relevance to the pharmaceutical industry, who are constantly
      searching for controllable, information-rich, high-throughput, environmentally
      friendly methods of producing products with a high degree of chemical
      selectivity. This chapter reviews the current and future applications of
      microreactors that could enhance the drug discovery process.

PMID- 19763462
TI  - The Electroosmotic Flow (EOF).
AB  - Controlling and manipulating liquids and analytes at the sub-millimeter scale is
      a challenge that frequently requires new methods to be developed. Indeed, scaling
      down of traditional macroscopic ideas often fails. For instance, pumping liquids
      using pressure differences is often impractical and counterproductive because the
      resulting parabolic flow profile deforms sample zones. As the size of the system
      shrinks, the surface-to-volume ratio increases and interfacial effects become
      dominant. This actually opens new possibilities since the phenomenon of
      electroosmotic flow (EOF), wherein a fluid is made to move relative to a
      stationary charged boundary, can then be exploited to design efficient
      microfluidic devices. In this chapter, we review the fundamental principles of
      EOF as well as some of the methods used to coat channel walls and reduce the
      impact of EOF in situations where it would be unfavorable for the device
      performance.

PMID- 19763463
TI  - Microengineered neural probes for in vivo recording.
AB  - One of the great challenges facing medicine is the repair of the damaged nervous
      system. Due to the limited capacity of the central (and to a lesser extent the
      peripheral) nervous systems to regenerate, damage such as spinal cord injury can
      often result in permanent paralysis. Researchers are attempting to overcome nerve
      injury by devising methods of sensing neural activity either in the brain or in
      the spinal cord or peripheral nervous system. This information can act as a
      control mechanism for either muscle stimulators (e.g. for restoring limb
      function) or providing function in some other way (such as controlling a cursor
      on a computer screen). Ideally, sensing devices are implanted into the body,
      directly accessing the nervous system. Whilst great advancements have been made
      in implantable neural stimulators, sensing of neural activity has proven to be a
      more difficult task. This chapter describes how microengineered probes allow
      construction of neuron-sized neural interfaces for enhanced recording in vivo.

PMID- 19763464
TI  - Impedance spectroscopy and optical analysis of single biological cells and
      organisms in microsystems.
AB  - A novel microfabricated flow cytometer for simultaneous impedance and optical
      measurement of single cells and particles is described in this chapter. We
      discuss the sensitivity of the system with regard to the impedance sensor and
      describe the optical setup. The relevant parameters related to the experimental
      setup and sample preparation are discussed. The use of dielectrophoretic forces
      for particle manipulation is presented as a simple enabling technology, which
      allows the manipulation of particles within microfluidic devices. The fabrication
      processes required to produce the impedance sensor chips are described with
      relevance to the chip design and features. Finally, the system is used to
      discriminate between different marine algae populations.

PMID- 19763465
TI  - Dielectrophoresis as a cell characterisation tool.
AB  - Dielectrophoresis (DEP) is a technique which offers label-free measurement of
      cell electrophysiology by monitoring its movement in non-uniform electric fields.
      In this chapter, the theory underlying DEP is explored, as are the implications
      of the development of equipment for taking such measurements. Practical
      considerations such as the selection of a suspending medium are also discussed.

PMID- 19763466
TI  - AC-electrokinetic applications in a biological setting.
AB  - Dielectrophoresis is a phenomenon which can be exploited to provide significant
      quantitative electrophysiological data in a range of biochemical setting, from
      oncology to drug discovery. This chapter seeks to elucidate those applications
      and the electrophysiological phenomena underpinning those applications.

PMID- 19763467
TI  - Wireless endoscopy: technology and design.
AB  - In this chapter we review the current capsule technology and the more
      conventional "gold standard" technologies against which the wireless devices are
      compared. Over the years there have been several implementations of capsule
      devices of growing sophistication as new technology has become available. A
      notable feature is the extent to which the devices available at any given time
      have relied upon other more mainstream technologies from which capsule builders
      have been able to borrow. As an inevitable consequence, device complexity and
      functionality have increased.

PMID- 19763468
TI  - Examination of the brain mitochondrial lipidome using shotgun lipidomics.
AB  - Contamination from subcellular organelles and myelin has hindered attempts to
      characterize the lipidome of brain mitochondria. A high degree of mitochondrial
      purity is required for accurate measurements of the content and molecular species
      composition of mitochondrial lipids. We devised a discontinuous Ficoll and
      sucrose gradient procedure for the isolation and purification of brain
      mitochondria free from any detectable contamination. Shotgun lipidomics was used
      to analyze the lipid composition of the brain mitochondria. These procedures can
      be used to determine whether intrinsic lipid abnormalities underlie mitochondrial
      dysfunction associated with neurological and neurodegenerative diseases.

PMID- 19763469
TI  - Tracking the glycerophospholipid distribution of docosahexaenoic acid by shotgun
      lipidomics.
AB  - Docosahexaenoic acid (DHA, 22:6 n-3) is an omega-3 fatty acid with a 22 carbon
      acyl chain containing six cis double bonds and is predominantly found in membrane
      glycerophospholipids. Dietary consumption of DHA has been positively linked with
      the prevention of numerous pathologies and consequently, it has been the focus of
      extensive research over the last four decades. Nevertheless, our understanding of
      its molecular mode of action is not well understood. One likely mechanism is
      through DHA's influence on cell membranes and the proteins embedded within them.
      This influence may be altered depending on the glycerophospholipid head group DHA
      is esterified to and its fatty acid partner, i.e., the specific
      glycerophospholipid molecule. Accordingly, an understanding of the exact
      glycerophospholipid distribution of DHA within a tissue is important if we wish
      to gain further insight into its role in the prevention of disease. In this
      chapter a rapid, shotgun lipidomic approach for identifying the molecular
      glycerophospholipid distribution of DHA is described.

PMID- 19763470
TI  - Global analysis of retina lipids by complementary precursor ion and neutral loss
      mode tandem mass spectrometry.
AB  - Despite an increasing recognition of the causative and diagnostic role of lipids
      in the onset and progression of retinal disease, information on the global lipid
      profile of the normal retina is quite limited. Here, a "shotgun" tandem mass
      spectrometry approach involving the use of multiple lipid class-specific
      precursor ion and neutral loss scan mode experiments has been employed to analyze
      lipid extracts from normal rat retina, obtained with minimal sample handling
      prior to analysis. Redundant information for the identification and
      characterization of molecular species in each lipid class was obtained by
      complementary analysis of their protonated or deprotonated precursor ions, or by
      analysis of their various ionic adducts (e.g., Na+, NH4+, Cl-, CH3OCO2-).
      Notably, "alternative" precursor ion or neutral loss scan mode MS/MS experiments
      are introduced that were used to identify rat retina lipid molecular species that
      were not detected using "conventional" scan types typically employed in large
      scale lipid-profiling experiments. This chapter outlines the principles and
      advantages of utilizing complementary/redundant identification of lipid species
      as a strategy to overcome inherent challenges and limitations of shotgun lipid
      analysis, and provides examples of the application of this strategy in the
      analysis of the retina lipidome.

PMID- 19763471
TI  - Combining lipidomics and proteomics of human cerebrospinal fluids.
AB  - Lipids from dietary sources or from de novo synthesis are transported while bound
      to proteins to other tissues where they are used for cell membrane synthesis or
      stored for energy generation. In cell membranes or in plasma, lipids can undergo
      several modifications that are important in cell function. Several proteins
      orchestrate the transport, biosynthesis, and modification of lipids. Thus, the
      intersection of lipids and proteins is important in human metabolic pathways.
      Recent advances in mass spectrometry and bioinformatics have made it possible to
      obtain compositional (structural and functional) data of lipid molecular species
      and proteins in biological samples. This combination of lipidomics and proteomics
      is advantageous because it allows us to better define biochemical pathways,
      discover new drug targets, and better understand the pathophysiology of several
      diseases.

PMID- 19763472
TI  - Lipid profiling using two-dimensional heteronuclear single quantum coherence NMR.
AB  - The use of NMR spectroscopy in lipid research has been traditionally reserved for
      the analysis and structural elucidation of discrete lipid molecules. Although NMR
      analysis of organic molecules provides a plethora of structural information that
      is normally unattainable by most other techniques, its use for global analysis of
      mixed lipid pools has been hampered by its relatively low sensitivity and
      overlapping of signals in the spectrum. However, the last few decades have
      witnessed great advancements in NMR spectroscopy that generally resulted in
      greater sensitivity and offered more flexibility in sampling techniques. The
      method discussed in this chapter describes the use of NMR for global lipidome
      analysis. This methodology benefits from the quantitative nature of this
      technique together with the abundance of the structural information it can offer,
      while partially overcoming the problems of low sensitivity and overlapping
      signals through isotope-enrichment and the use of multidimensional NMR,
      respectively. We have applied this method successfully to the mycobacterial
      lipidome as an example of an organism with a very complex and chemically diverse
      lipid pool. The same concept is applicable to a wide range of prokaryotes that
      can grow in the laboratory in well-defined growth media.

PMID- 19763473
TI  - Capabilities and drawbacks of phospholipid analysis by MALDI-TOF mass
      spectrometry.
AB  - The important roles of lipids particularly certain phospholipids in signal
      transduction processes and as important disease markers are becoming increasingly
      evident. Unfortunately, however, sensitive methods of lipid analysis are
      established to a much lesser extent than, e.g., methods of protein analysis. Mass
      spectrometry (MS) is an increasingly used technique of lipid analysis and
      electrospray ionization (ESI) MS is the so far most established ionization
      method. Although matrix-assisted laser desorption and ionization time-of-flight
      mass spectrometry (MALDI-TOF MS) was so far primarily used for protein analysis,
      however, this method has itself proven to be very useful in the field of lipid
      analysis, too. This chapter gives an overview of methodological aspects of MALDI
      TOF MS in lipid research and summarizes the specific advantages and drawbacks of
      this soft-ionization method. In particular, suppression effects of some lipid
      classes, especially those with quaternary ammonia groups such as
      phosphatidylcholine, will be highlighted and possible ways to overcome this
      problem (use of different matrices, separation of the relevant lipid mixture
      prior to analysis) will be discussed on the example of an organic liver extract.

PMID- 19763474
TI  - Lipidomics of the red cell in diagnosis of human disorders.
AB  - Applications of tandem mass spectrometry in the field of lipid clinical chemistry
      are considered. Haemato-logical and biochemical advantages are presented favoring
      the choice of red blood cell membranes as a starting material in a wide variety
      of biomedical fields. Practical considerations are discussed with respect to
      methods of sampling, storage, and lipid extraction of red blood cells. The
      chapter describes the capabilities of a direct infusion of raw lipid extracts in
      the electro-spray ionization source compared with the more sophisticated method
      of high-performance liquid chromatography coupled with hybrid tandem mass
      spectrometry. Both methods have been evaluated and have been shown to be suitable
      for diagnosis and/or monitoring for a variety of human disorders.

PMID- 19763475
TI  - HPLC/MS/MS-based approaches for detection and quantification of eicosanoids.
AB  - Eicosanoids are oxygenated, endogenous, unsaturated fatty acids derived from
      arachidonic acid. Detection and quantification of these compounds are of great
      interest because they play important roles in a number of significant diseases,
      including asthma, chronic obstructive pulmonary disease (COPD), cardiovascular
      disease, and cancer. Because the endogenous levels of eicosanoids are quite low,
      sensitive and specific analytical methods are required to reliably quantify these
      compounds. High-performance liquid chromatography mass spectrometry (HPLC/MS) has
      emerged as one of the main techniques used in eicosanoid profiling. Herein, we
      describe the main LC/MS techniques and principles as well as their application in
      eicosanoid analysis. In addition, a protocol is given for extracting eicosanoids
      from biological samples, using bronchoalveolar lavage fluid (BALF) as an example.
      The method and instrument optimization procedures are presented, followed by the
      analysis of eicosanoid standards using reverse phase HPLC interfaced with an ion
      trap mass spectrometer (LC/MS/MS). This protocol is intended to provide a broad
      description of the field for readers looking for an introduction to the
      methodologies involved in eicosanoid quantification.

PMID- 19763476
TI  - Brain phosphoinositide extraction, fractionation, and analysis by MALDI-TOF MS.
AB  - Matrix-assisted laser desorption and ionization time-of-flight (MALDI-TOF) mass
      spectrometry (MS) can provide rapid, sensitive determinations of lipids from
      small tissue samples in both single determinations and automated high-throughput
      assays. MALDI-TOF MS is a sensitive, high-throughput technique for the
      determination of lipids such as the phosphoinositides, PtdIns
      (phosphatidylinositol), PIP (phosphatidylinositol-4-phosphate, and PIP2
      (phosphatidylinositol-4,5-bisphosphate), but in crude extracts the signals are
      weak or not observed due in large part to ion suppression by phosphatidylcholine
      and other cationic lipids. A rapid separation step using a small column of a
      strong cation exchange (SCX) gel can be utilized easily and effectively to adsorb
      or capture cationic lipids from chloroform/methanol lipid extracts and provide
      substantially improved signals for the phosphoinositides. In this review, we
      describe the use of fractionation of a crude lipid extracts using cation exchange
      columns in conjunction with MALDI-TOF MS and appropriate internal standards to
      quantify the levels of phosphoinositides in small mammalian brain samples.

PMID- 19763477
TI  - Lipidomic analysis of biological samples by liquid chromatography coupled to mass
      spectrometry.
AB  - Lipidomics studies the large-scale changes in nonwater-soluble metabolites
      (lipids) accompanying perturbations of biological systems. Because lipids are
      involved in crucial biological mechanisms, there is a growing scientific interest
      in using lipidomic approaches to understand the regulation of the lipid
      metabolism in all eukaryotic and prokaryotic organisms. Lipidomics is a powerful
      tool in system biology that can be used together with genomics, transcriptomics,
      and proteomics to answer biological questions arising from various scientific
      areas such as environmental sciences, pharmacology, nutrition, biophysics, cell
      biology, physiology, pathology, and disease diagnostics. One of the main
      challenges for lipidomic analysis is the range of concentrations and chemical
      complexity of different lipid species. In this chapter, we present a lipidomic
      approach that combines sample preparation, chromatographic, and intrasource
      ionization separation coupled to mass spectrometry for analyzing a broad-range of
      lipid molecules in biological samples.

PMID- 19763478
TI  - Lipidomic analysis of human meibum using HPLC-MSn.
AB  - High-pressure liquid chromatography-mass spectrometry (HPLC-MS) has become a de
      facto standard analytical tool in lipidomic analyses of complex biological
      samples. This technique offers the best combination of selectivity and
      sensitivity among the currently available analytical methods, and provides not
      only the retention times of analytes, but also their m/z values, from which
      molecular masses of the compounds can be deduced. Further enhancement of the
      technique comes from the fact that some of the MS instruments (also known as ion
      traps, or MSn instruments) are capable of multistage fragmenting of the analytes,
      thus enabling the researcher to perform their structural elucidation. These
      capabilities make HPLC-MSn an ideal tool for analyzing small, complex lipid
      samples such as human meibum. Meibum is a very complex lipid mixture which is
      secreted onto the ocular surface by Meibomian glands. Meibum plays a critical
      role in the biochemistry and physiology of the human ocular surface. However,
      despite all efforts, its (bio)chemical composition remains elusive. In this
      chapter, several HPLC-MSn methods developed for lipidomic analysis of human
      meibum will be discussed. Considering the nature of analytes (all of which are
      hydrophobic compounds poorly soluble in water, and most of which are
      electroneutral), the only MS technique used in the study will be atmospheric
      pressure chemical ionization (APCI) MSn in both the positive and the negative ion
      modes. Electrospray ionization technique, though useful in phospholipid analyses,
      was found to be inadequate for analyzing less polar compounds, such as wax
      esters. As the data provided in this chapter will show that meibum is composed
      predominantly of nonpolar lipids of wax ester, cholesteryl ester, and
      triacylglycerol families with no appreciable amounts of more polar lipids
      present, APCI MSn seems to be a method of choice for lipidomic analysis of meibum
      and similar lipid mixtures.

PMID- 19763479
TI  - Lipid geographical analysis of the primate macula by imaging mass spectrometry.
AB  - Imaging mass spectrometry (IMS) provides a unique method to probe for chemical
      distributions within tissue sections with high chemical specificity. The direct
      analysis of tissue sections by mass spectrometry, which is the field of IMS, is
      relatively young, 10 year old; however, the techniques for mass spectrometric
      analysis are well known. Critical aspects of IMS then are the preparation of
      tissue specimens for insertion into a vacuum chamber and the interpretation of
      results with respect to disease studies. Here, we describe the methodologies for
      geographic localization of phospholipids in flat-mounted eye segments from rhesus
      monkey using IMS with matrix-assisted laser desorption/ionization (MALDI) and
      tandem mass spectrometry.

PMID- 19763480
TI  - A novel role for nutrition in the alteration of functional microdomains on the
      cell surface.
AB  - Membrane rafts are ordered microdomains of the plasma membrane consisting of
      cholesterol, sphingolipids, and saturated fatty acids which appear to regulate
      many cellular signaling pathways. One such type of membrane raft is caveolae,
      which are cave-like invaginations of the plasma membrane. Interestingly, changes
      in the acyl composition of cellular membranes have been shown to alter the
      specific localization of membrane raft associated proteins and their function.
      This is noteworthy because modification of membrane acyl composition is readily
      accomplished through changes in dietary fat composition. Here we describe a
      common approach used to fractionate cell membranes to obtain an enriched
      preparation of caveolae and gas chromatographic techniques to determine fatty
      acyl composition. In addition, methods used to visualize and quantify lipid rafts
      using a fluorescent probe Laurdan in living cells will also be described.

PMID- 19763481
TI  - Lipidomic analysis of prostanoids by liquid chromatography-electrospray tandem
      mass spectrometry.
AB  - Lipidomics aim to generate qualitative and quantitative information on different
      classes of lipids and their species, and when applied in conjunction with
      proteomic and genomic assays, facilitate the comprehensive study of lipid
      metabolism in cellular, organ, or body systems. Advances in mass spectrometry
      have underpinned the expansion of lipidomic methodologies. Prostanoids are potent
      autacoids present in a plethora of cellular systems, known best for their
      intimate role in inflammation. Electrospray ionisation (ESI) allows the efficient
      ionisation of prostanoids in aqueous systems. ESI can be readily coupled to
      liquid chromatography (LC) followed by tandem mass spectrometry (MS/MS)-based
      detection, thus allowing the development of a potent and selective LC/ESI-MS/MS
      quantitative assays. The protocol we describe in this chapter outlines the steps
      we follow to (a) extract prostanoids from solid or liquid samples, (b) semi
      purify the metabolites using solid phase extraction (c) set-up the HPLC
      separation using reverse phase chromatography and (d) set-up the MS/MS assay
      using a triple quadrupole mass spectrometer. The experimental details and notes
      presented here are based on the detailed protocols followed in our group.

PMID- 19763482
TI  - Qualitative and quantitative analyses of phospholipids by LC-MS for lipidomics.
AB  - In this chapter we are going to mention about three different approaches in
      lipidomics and how to effectively profile or calculate the amounts of
      phospholipids from major molecular species up to minor ones. 1) Precise
      identification and profiling of individual molecular species of phospholipids by
      data-dependent LC-ESIMS/MS combination with "Lipid Search". We have been using
      this method as a global analysis of phospholipid. We usually applied this method
      at least once for new biological samples. We constructed an automated search
      engine, "Lipid Search", for identification and profiling of phospholipids. Once
      after applying this analysis, a specified retention time can be obtained for each
      elution peak of individual phospholipid molecular species. Thus, reproducible
      identification results can be effectively obtained by our search engine from the
      data obtained by single LC or combination of LC with specified head group survey
      by using precursor ion scanning or neutral loss scanning. 2) An effective
      analytical method of LC-ESIMS for the identification of acidic phospholipids such
      as phosphatidic acid and phosphatidylserine. This is an approach of how to obtain
      sharp chromatographic peaks for acidic lipids such as phosphatidic acid and
      phosphatidylserine that are normally detected as broad elution peaks. With this
      improvement very small amount of molecular species in minor acidic phospholipids
      were effectively obtained. 3) Identification and profiling of molecular species
      in focused phospholipids. Third one is a combination analysis of focused methods
      such as precursor ion scanning or neutral loss scanning and high efficient LC
      separation. As reported previously, different combinations of fatty acids on sn-1
      and sn-2 can be mostly detected as separate peaks by reverse phase LC-ESIMS.
      Detection limit of precursor ion scanning or neutral loss scanning is more than
      ten times higher than that of the method without LC separation, because of
      decreased ion suppression. We will mention about application of this methods for
      focused analysis on phosphatidylethanolamine-plasmalogens.

PMID- 19763483
TI  - Determination of fatty acid profiles and TAGs in vegetable oils by MALDI-TOF/MS
      fingerprinting.
AB  - Vegetable oils are complex mixtures containing a wide range of major compounds.
      Triacylglycerols (TAGs; consisting of a glycerol moiety with each hydroxyl group
      esterified to a fatty acid) are the major components (95-98%) of vegetable oils.
      TAGs are an important source of energy and nutrition for humans, so their
      compositional analysis merits extensive interest. Analysis of TAGs has increased
      in recent years and the advancement has been driven by the development of
      analytical technologies. This chapter discusses techniques for determination of
      TAG and fatty acid profiles (FAPs) of vegetable oils using matrix-assisted laser
      desorption/ionization-time of flight mass spectrometry (MALDI-TOF/MS) and gas
      chromatography-mass spectrometry (GC/MS). Considering the importance of TAG in
      its native form, rather than FAPs, special emphasis has been given to the TAG
      fingerprinting analyses of intact oils. MALDI-TOF/MS also enabled calculation of
      the main fatty acids and their compositions in a simple manner from the TAG
      profiles; the results are found to be very similar to the prevailing methods of
      derivatization using GC/MS. This study depicts the potential of MALDI-TOF/MS as
      an easy, fast, and reliable technique to characterize the TAG and FAPs in
      vegetable oils.

PMID- 19763484
TI  - Dynamics of adipose tissue development by 2H2O labeling.
AB  - Adipose tissue development undergoes remodeling in terms of newly synthesized
      cells (hyperplasia) and newly synthesized lipids that accumulate in adipocytes
      (hypertrophy). Synthesis and/or breakdown rates of adipose cells and lipids
      follow a continuous and dynamic pattern, e.g., during obesity development. This
      chapter describes a unique in vivo method to measure the dynamics of adipose
      tissue growth using 2H2O labeling and mass spectrometry analyses. The approach
      uses 2H2O as a metabolic tracer to label the adipose tissue components such as
      the triglycerides (TG), the fatty acids, and the genomic DNA. Deuterium from 2H2O
      incorporates in the C-H bonds of glycerol moiety of TG through glyceroneogenesis
      as well as in palmitate moiety through de novo lipogenesis (DNL). Deuterium also
      incorporates into DNA through the de novo nucleoside synthesis pathway. The
      labeled water, 2H2O, is administrated intraperitoneally and/or orally in rodents
      or in humans for a defined duration and biopsies are collected at the end of the
      labeling period. We describe the procedure to extract, isolate, and purify the
      adipose components (TG-glycerol, TG-palmitate, and genomic DNA) and the
      derivation procedure to analyze the isotopic 2H-enrichment of these components by
      gas chromatography/mass spectrometry. The calculation principles are described to
      obtain the fractional and absolute synthesis rates of TG, of DNL, and of DNA
      measured in the adipose tissues. The method is nonradioactive, nonhazardous,
      accurate, reproducible, and very sensitive. We present recent in vivo data on the
      ontogeny of adipose tissue growth dynamics in young and adult obese Zucker rats
      compared with lean Zucker rats.

PMID- 19763485
TI  - Analysis of lipid particles from yeast.
AB  - Quantitative analysis of components from different subcellular fractions is a key
      to the understanding of metabolic function as well as to the origin, the
      biogenesis, and the crosstalk of organelles. The yeast is an excellent model
      organism to address such questions from the biochemical, molecular biological,
      and cell biological viewpoints. A yeast organelle which gained much interest
      during the last decade is the lipid particle/droplet (LP), a storage compartment
      for nonpolar lipids but at the same time an organelle actively contributing to
      cellular metabolism. In this chapter, we describe methods and techniques that are
      commonly used to analyze lipids from LP at the molecular level by thin-layer
      chromatography, gas-liquid chromatography, and mass spectrometry. We provide an
      easy to follow guideline for the isolation of these organelles, the qualitative
      and quantitative analysis of lipid components and show results obtained with
      these methods.

PMID- 19763486
TI  - Mammalian fatty acid elongases.
AB  - Very long chain fatty acids confer functional diversity on cells by variations in
      their chain length and degree of unsaturation. Microsomal fatty acid elongation
      represents the major pathway for determining the chain length of saturated,
      monounsaturated, and polyunsaturated fatty acids in cellular lipids. The overall
      reaction for fatty acid elongation involves four enzymes and utilizes malonyl
      CoA, NADPH, and fatty acyl CoA as substrates. While the fundamental pathway and
      its requirements have been known for many years, recent advances have revealed a
      family of enzymes involved in the first step of the reaction, i.e., the
      condensation reaction. Seven fatty acid elongase subtypes (Elovl #1-7) have been
      identified in the mouse, rat, and human genomes. These enzymes determine the rate
      of overall fatty acid elongation. Moreover, these enzymes also display
      differential substrate specificity, tissue distribution, and regulation, making
      them important regulators of cellular lipid composition as well as specific
      cellular functions. Herein, methods are described to measure elongase activity,
      analyze elongation products, and alter cellular elongase expression.

PMID- 19763487
TI  - Membrane lipidomics and the geometry of unsaturated fatty acids from biomimetic
      models to biological consequences.
AB  - In the last decades, free radical processes delineated an interdisciplinary field
      linking chemistry to biology and medicine. Free radical mechanisms became of
      importance as molecular basis of physiological and pathological conditions.
      Lipids, in particular, unsaturated fatty acids, are susceptible of free radical
      attack. The reactivity of the double bond toward free radicals is well known, in
      particular the reversible addition of radical species to this functionality
      determines the cis-trans double bond isomerization. Since the prevalent geometry
      displayed by unsaturated fatty acids in eukaryotes is cis, the occurrence of the
      cis-trans isomerization by free radicals corresponds to the loss of an important
      structural information linked to biological activity. The formation of trans
      isomers can have important meaning and consequences connected to radical stress.
      Free radical isomerization of membrane fatty acids has been the subject of
      research coupling the top-down approach by model studies, such as biomimetic
      chemistry in liposomes, with the bottom-up approach dealing with the examination
      of cell membrane lipidome in living systems under several physiopathological
      conditions. Methodologies and molecular libraries have been settled, for both
      liposome experiments and the examination of the radical stress in biological
      membranes. This chapter will give an overview of the current procedures used for
      liposome models and the cis-trans isomerization experiments, in order to build-up
      a library of trans geometrical fatty acid isomers.

PMID- 19763488
TI  - OnLine ozonolysis methods for the determination of double bond position in
      unsaturated lipids.
AB  - Modern lipidomics relies heavily on mass spectrometry for the structural
      characterization and quantification of lipids of biological origins. Structural
      information is gained by tandem mass spectrometry (MS/MS) whereby lipid ions are
      fragmented to elucidate lipid class, fatty acid chain length, and degree of
      unsaturation. Unfortunately, however, in most cases double bond position cannot
      be assigned based on MS/MS data alone and thus significant structural diversity
      is hidden from such analyses. For this reason, we have developed two online
      methods for determining double bond position within unsaturated lipids; ozone
      electrospray ionization mass spectrometry (OzESI-MS) and ozone-induced
      dissociation (OzID). Both techniques utilize ozone to cleave C-C double bonds
      that result in chemically induced fragment ions that locate the position(s) of
      unsaturation.

PMID- 19763489
TI  - Comprehensive quantitative analysis of bioactive sphingolipids by high
      performance liquid chromatography-tandem mass spectrometry.
AB  - There has been a recent explosion in research concerning novel bioactive
      sphingolipids (SPLs) such as ceramide (Cer), sphingosine (Sph), and sphingosine 1
      phosphate (Sph-1P) and this has necessitated the development of accurate and user
      friendly methodology for analyzing and quantitating the endogenous levels of
      these molecules. ESI/MS/MS methodology provides a universal tool used for
      detecting and monitoring changes in SPL levels and composition from biological
      materials. Simultaneous ESI/MS/MS analysis of sphingoid bases (SBs), sphingoid
      base 1-phosphates (SB-1Ps), ceramides (Cers), ceramide 1-phosphates (Cer-1P),
      glucosyl/galactosyl-ceramides (Glu-Cers), and sphingomyelins (SMs) is performed
      on a Thermo Fisher Scientific triple quadrupole mass spectrometer operating in a
      multiple reaction monitoring (MRM) positive ionization mode. Biological materials
      (cells, tissues, or physiological fluids) are fortified with internal standards
      (ISs), extracted into a one-phase neutral organic solvent system, and analyzed by
      a LC/MS/MS system. Qualitative analysis (identification) of SPLs is performed by
      a Parent Ion scan of a common fragment ion characteristic for a particular class
      of SPLs. Quantitative analysis is based on calibration curves generated by
      spiking an artificial matrix with known amounts of target analyte, synthetic
      standards, and an equal amount of IS. The calibration curves are constructed by
      plotting the peak area ratios of analyte to the respective IS against
      concentration, using a linear regression model. This robust analytical procedure
      can determine the composition of endogenous sphingolipids (ESPLs) in varied
      biological materials and achieve a detection limit of subpicomole level. This
      methodology constitutes a "Lipidomic" approach to study the SPLs metabolism,
      defining a function of distinct subspecies of individual bioactive SPL classes.

PMID- 19763490
TI  - The use of charged aerosol detection with HPLC for the measurement of lipids.
AB  - A gradient HPLC-charged aerosol detection method was applied to the measurement
      of different lipids including: free fatty acids, fatty alcohols, glycerides,
      steroids, phospholipids, and fat-soluble vitamins. An algal oil sample is used as
      an example. Charged aerosol detection offers a new approach to the routine
      analysis of any nonvolatile lipid. It shows low ng (on column) sensitivity, a
      dynamic range of over four orders of magnitude, good reproducibility, gradient
      compatibility, and similar analyte response for nonvolatile species, independent
      of chemical structure. Furthermore, charged aerosol detection uses mobile phases
      that are fully compatible with LC-MS--enabling both detectors to be used in a
      "lipidomics platform."

PMID- 19763491
TI  - Non-invasive mapping of lipids in plant tissue using magnetic resonance imaging.
AB  - Plant oil has become an important component in the search for a replacement for
      non-renewable energy sources, as well as being used for a wide range of
      industrial purposes, all in addition to its vital importance for human diet.
      Detailed knowledge of the lipid distribution in plants is fundamental for the
      understanding of local regulatory networks covering storage metabolism, and for
      the development of new approaches for plant breeding and transgenic research. We
      here review a measurement protocol or "tool" based on magnetic resonance imaging
      (MRI), which allows the non-invasive detection and quantitative visualization of
      lipid in living plant tissue. The method provides quantitative lipid maps with a
      resolution close to the cellular level and can be used on a wide range of plants
      and is applicable at the level of individual tissues, organs, or entire plants
      during ontogeny. Lipid imaging is designed for both biotechnology and basic
      science and can be combined with histological, biochemical, and gene expression
      analysis. Here we present the method as practiced in our group, and discuss
      unique advantages and limitations of the lipid-imaging tool. Seeds of barley and
      rapeseed were used as a model for visualization of local oil accumulation at the
      organ- and tissue-specific scale.

PMID- 19763492
TI  - Mapping the lipolytic proteome of adipose tissue using fluorescent suicide
      inhibitors.
AB  - Lipases are responsible for the hydrolysis of acylglycerols and cholesteryl
      esters in animals, plants, and microorganisms. In this chapter we describe a tool
      for the concomitant analysis of lipases in complex proteomes. For this purpose,
      the target enzymes are selectively and covalently labelled with fluorescent
      suicide inhibitors. Stable lipid-protein complexes are formed that are separated
      by gel electrophoresis and identified by mass spectrometry.

PMID- 19763493
TI  - Identifying the spatial distribution of vitamin E, pulmonary surfactant and
      membrane lipids in cells and tissue by confocal Raman microscopy.
AB  - Every organ compromises of several different cell types. When studying the
      effects of a chosen compound within this organ or tissue uptake, localisation,
      metabolism, and the effect itself can be expected to differ between cells. Using
      the example of Vitamin E in pulmonary tissue we introduce confocal Raman
      Microscopy as a superior method to localise lipid-soluble compounds within
      tissues and cells. We describe the analyses of vitamin E, its oxidation products,
      and metabolites as well as pulmonary surfactant phospholipids in fixed lung
      tissue sections. Examples of main structural membrane lipids (PC, cholesterol)
      and an example of a lipid-signalling molecule (ceramide) are also included.
      Confocal Raman microscopy is a non-destructive optical method of analysing
      chemical and physical composition of solids, liquids, gases, gels, and solutions.
      The method is rich in information allowing discrimination of chemically similar
      molecules (including geometric isomers) and sensitive monitoring of subtle
      physical interactions. Additionally, Raman spectroscopy is relatively insensitive
      to water allowing the analysis of aqueous solutions and suspensions typical in
      biochemistry. In contrast, Raman spectroscopy is sensitive to non-polar molecules
      making it ideal for lipidomics research.

PMID- 19763494
TI  - Determining the affinity of hormone-receptor interaction.
AB  - Characterization of the binding of a hormone to its cognate receptor is a
      cornerstone of many studies in molecular and cellular endocrinology since this
      event represents the beginning of a specific cellular response, generally from a
      highly regulated extracellular messenger. The premise of hormone-receptor
      interaction follows from the law of mass action describing a reversible second
      order reaction, hormone plus receptor, to give a non-covalently associated
      hormone-receptor complex. From this basic principle, a host of useful
      experimental parameters are available to the interested investigator. This
      chapter is focused on development of the experimental and mathematical
      underpinning of hormone-receptor interaction, with emphasis on a gonadotropin,
      chorionic gonadotropin (or luteinizing hormone), binding to the luteinizing
      hormone receptor, a member of the G protein-coupled receptor family. The general
      concepts and approaches developed herein are, however, valid to most interacting
      systems.

PMID- 19763495
TI  - Determination of serum estradiol levels by radiometric and chemiluminescent
      techniques.
AB  - The ability to precisely measure circulating levels of hormones is a foundation
      of modern endocrinology. For assisted reproductive technologies such as in vitro
      fertilization (IVF), accurate determination of circulating levels of estradiol
      are crucial for patient management, retrieval of fertilizable oocytes, and
      successful pregnancy outcome. For many years, circulating levels of estradiol
      were determined by radioimmunoassay. More recently, nonradioactive techniques
      such as ELISAs or chemiluminescent approaches have replaced traditional
      radioimmunoassays. In the current chapter, we outline the procedures for analysis
      of circulating levels of estradiol by both radioimmunoassay and chemiluminescent
      techniques.

PMID- 19763496
TI  - Identification of natural human glucocorticoid receptor (hGR) mutations or
      polymorphisms and their functional consequences at the hormone-receptor
      interaction level.
AB  - Glucocorticoids regulate a broad spectrum of physiologic functions essential for
      life and play an important role in the maintenance of basal and stress-related
      homeostasis. At the cellular level, the actions of glucocorticoids are mediated
      by the human glucocorticoid receptor alpha (hGRalpha), a ligand-dependent
      transcription factor ubiquitously expressed in almost all tissues and cells. The
      molecular mechanisms of hGRalpha action involve (a) binding to glucocorticoids,
      (b) cytoplasmic to nuclear translocation, (c) binding/association to
      DNA/chromatin, and (d) transcriptional activation or repression by interacting
      with cofactors and other transcription factors. Mutations or polymorphisms in the
      hGR gene may impair these molecular mechanisms of hGRalpha action, thereby
      altering tissue sensitivity to glucocorticoids. The latter may take the form of
      glucocorticoid resistance or glucocorticoid hypersensitivity and may be
      associated with significant morbidity. The identification of natural pathologic
      mutations in patients' hGR gene and the subsequent examination of the functional
      defects of the natural mutant hGRalpha receptors would enhance our understanding
      of the molecular mechanisms of hGRalpha action and highlight the importance of
      integrated cellular and molecular signaling mechanisms for maintaining
      homeostasis and preserving normal physiology.

PMID- 19763497
TI  - Monitoring insulin-stimulated production of signaling lipids at the plasma
      membrane.
AB  - Lipid second messengers play important roles in many cell signaling cascades.
      Lipid signaling molecules allow for high specificity, rapid transduction, and
      rapid reversibility of localized stimulation events. Fluorescent sensors capable
      of detecting individual signaling lipids enable their production and degradation
      to be followed, revealing the nature and dynamics of signaling pathways. The
      following sections outline a method for using lipid sensors to monitor the
      production of signaling lipids on the plasma membrane of C2C12 myotubes in
      response to insulin signaling.

PMID- 19763498
TI  - Gene expression profiling in the aging ovary.
AB  - DNA microarray is an important discovery technology that allows the analysis of
      the expression of thousands of genes at a time. Data from DNA microarrays
      elucidate fundamental biological processes through discovery of differential
      expression of genes not previously known or predicted to be involved in a
      particular process. In the ovary and other hormone-responsive tissues, the
      technology can be used to examine the effects of gene mutations, pharmaceutical
      agents, disease, hormones, developmental changes, or changes in gene expression
      related to aging.

PMID- 19763499
TI  - Genomics analysis: endometrium.
AB  - Microarray technology has been used widely in gynecology. Numerous studies have
      used this method to address biological questions related to human endometrium.
      The cyclic changes of endometrium confer special characteristics that should be
      considered before genomic analysis. The present study reviews these
      considerations and the principles of transcriptomic analysis through an example
      of a comparison of three different phases of the menstrual cycle.

PMID- 19763500
TI  - Detection of ovarian matrix metalloproteinase mRNAs by in situ hybridization.
AB  - In situ hybridization represents a powerful technique to localize DNA or RNA of
      interest at the chromosomal or cellular level. In endocrine tissues composed of
      diverse and varied cell types, in situ hybridization has allowed the
      identification of specific cells responsible for the expression of genes
      controlling the function of the tissue. Our laboratory has routinely used this
      approach to understand the cellular expression of genes associated with the
      growth of the ovarian follicle, rupture of the follicle, and transformation of
      the ruptured follicle into the corpus luteum. The current study outlines the
      procedural details of in situ detection of mRNA in tissues and illustrates the
      utility of this approach in identifying the ovarian cells expressing the matrix
      metalloproteinases and their endogenous inhibitors, the TIMPs, in the human
      ovary.

PMID- 19763501
TI  - Adenoviral gene transfer into isolated pancreatic islets.
AB  - The beta cells within the pancreatic islets are responsible for production of
      insulin, a peptide hormone required for maintaining normoglycemia. The
      establishment of efficient gene transfer into pancreatic islets is very important
      for studies of insulin and glucagon production and secretion, as well as for gene
      therapy purposes for the treatment of diabetes. We describe here in detail a
      protocol for adenoviral gene transfer into isolated mouse islets of the pancreas.
      Effective gene transfer into pancreatic islets using recombinant adenoviruses can
      be achieved with a multiplicity of infection (MOI) of 10. However, if the islets
      are not dispersed, adenoviral gene transfer is limited only to the cells on the
      periphery of the islets, which represent the glucagon-producing alpha cells in
      rodents. Dispersion of pancreatic islets with EGTA increases the efficiency of
      gene transfer into the cells within the core of the islets, which consist of
      insulin-producing beta cells.

PMID- 19763502
TI  - Basic molecular techniques for the detection of single nucleotide polymorphisms:
      genome-wide applications in search for endocrine tumor related genes.
AB  - The necessity of genotyping high number of variations in extended sample sets has
      become apparent in the era of large genomic studies of common complex disorders,
      in cancer and in pharmacogenomics. The single nucleotide polymorphisms' (SNPs)
      apparent advantages over other genetic markers such as high frequency, relative
      stability, and statistically random distribution across the genome have made them
      a method of choice for most of these genome-wide oriented applications. The
      requirement for simultaneous genotyping of high number of SNPs, keeping at the
      same time reasonable price and reliable accuracy, triggered the rise of the
      genotyping throughput, and led to the development of the array-based
      technologies. The present chapter briefly reviews the methodological and
      historical aspect of the basic SNP detecting techniques that lie in the basis of
      the modern high-throughput technologies, providing at the same time detailed
      guide on the application of one of the most advanced SNP microarray platform on
      the market: the genome-wide SNP Array 6.0 recently developed by Affymetrix, which
      we have used to study families with Catney complex and Micronodular
      adrenocortical hyperplasia. In addition, we discuss practical clues and tips
      aiming at extending applications and improving performance.

PMID- 19763503
TI  - Methylated DNA immunoprecipitation and microarray-based analysis: detection of
      DNA methylation in breast cancer cell lines.
AB  - The methylated DNA immunoprecipitation microarray (MeDIP-chip) is a genome-wide,
      high-resolution approach to detect DNA methylation in whole genome or CpG
      (cytosine base followed by a guanine base) islands. The method utilizes anti
      methylcytosine antibody to immunoprecipitate DNA that contains highly methylated
      CpG sites. Enriched methylated DNA can be interrogated using DNA microarrays or
      by massive parallel sequencing techniques. This combined approach allows
      researchers to rapidly identify methylated regions in a genome-wide manner, and
      compare DNA methylation patterns between two samples with diversely different DNA
      methylation status. MeDIP-chip has been applied successfully for analyses of
      methylated DNA in the different targets including animal and plant tissues. Here
      we present a MeDIP-chip protocol that is routinely used in our laboratory,
      illustrated with specific examples from MeDIP-chip analysis of breast cancer cell
      lines. Potential technical pitfalls and solutions are also provided to serve as
      workflow guidelines.

PMID- 19763504
TI  - Use of reporter genes to study the activity of promoters in ovarian granulosa
      cells.
AB  - Use of reporter genes provides a convenient way to study the activity and
      regulation of promoters and examine the rate and control of gene transcription.
      Many reporter genes and transfection methods can be efficiently used for this
      purpose. To investigate gene regulation and signaling pathway interactions during
      ovarian follicle development, we have examined promoter activities of several key
      follicle-regulating genes in the mouse ovary. In this chapter, we describe use of
      luciferase and beta-galactosidase genes as reporters and a cationic liposome
      mediated cell transfection method for studying regulation of activin subunit- and
      estrogen receptor alpha (ERalpha)-promoter activities. We have demonstrated that
      estrogen suppresses activin subunit gene promoter activity while activin
      increases ERalpha promoter activity and increases functional ER activity,
      suggesting a reciprocal regulation between activin and estrogen signaling in the
      ovary. We also discuss more broadly some key considerations in the use of
      reporter genes and cell-based transfection assays in endocrine research.

PMID- 19763505
TI  - Use of reporter genes to study promoters of the androgen receptor.
AB  - As a transcriptional regulator, the androgen receptor (AR) regulates the
      expression of many genes that are essential for male sexual differentiation,
      including the development of both normal prostate and prostate cancer. The AR
      acts by binding to regulatory DNA sequences found on the promoters of regulated
      genes. The study of AR activity on such responsive promoters is greatly
      facilitated by the use of the reporter gene assay, which provides a quantitative
      and reproducible method for studying the activity of such promoters. Among the
      several reporter genes that can be used, the genes encoding luciferase (Luc) and
      chloramphenicol acetyltransferase (CAT) have been used most widely and
      successfully by researchers interested in AR-regulated promoters. Such studies
      have led to the identification and characterization of DNA regulatory elements
      mediating AR activity on responsive promoters and to an improved understanding of
      how AR regulates the transcription process. Described in this chapter is a method
      by which to generate and utilize Luc and CAT reporter gene plasmids driven by the
      promoter of a novel androgen-regulated gene, ETV1.

PMID- 19763506
TI  - Isolation of proteins associated with the DNA-bound estrogen receptor alpha.
AB  - Regulating gene expression is a complex process requiring the interaction of
      multiple transcription factors with their cognate recognition sequences. While
      these DNA-bound transcription factors are the primary drivers of gene expression,
      the capacity of a transcription factor to alter gene expression is tempered by
      its association with a host of coregulatory proteins that are recruited to the
      DNA-bound transcription factor. We have developed a novel approach to isolate
      large complexes of proteins associated with the DNA-bound estrogen receptor alpha
      (ERalpha) using an agarose-based electrophoretic mobility shift assay (EMSA).
      This method should be readily adapted to a variety of cultured cell lines, DNA
      sequences, and transcription factors and has the potential to provide valuable
      information about a wide variety of regulatory proteins involved in influencing
      gene expression.

PMID- 19763507
TI  - Chromosome-wide analysis of protein binding and modifications.
AB  - In order to fully understand the functions of a DNA-binding protein it is
      necessary to identify all of its binding sites in chromosomes and assess the role
      of each site in the overall biological function of the factor. An approach ChIP
      on-Chip which combines the chromatin immunoprecipitation technique with
      chromosomal DNA microarray analysis, has proven to be a powerful means for the
      chromosome-wide identification of protein binding sites. This approach can also
      be used to characterize chromosome-wide variations in patterns of post
      translational protein modifications, for example histone modifications. This
      chapter presents methodologies for the ChIP-on-Chip analysis, using as an example
      the identification of chromosome-wide binding sites for the TATA-binding protein
      in mitotic cells.

PMID- 19763508
TI  - Genome-wide analysis for protein-DNA interaction: ChIP-chip.
AB  - Chromatin immunoprecipitation (ChIP) is a well-established procedure for protein
      DNA interaction research. ChIP-chip, combining chromatin immunoprecipitation
      (ChIP) and microarray technology (Chip), enables scientists to survey genome-wide
      DNA binding sites for a given protein. The ChIP-chip technique has been used to
      identify transcription factor binding sites, explore epigenomic information and
      investigate factors in DNA replicate/repairs. Here we describe a protocol for
      ChIP-chip to study Pituitary Tumor Transforming Gene (PTTG1) in mammalian cells.

PMID- 19763509
TI  - Detection of ERalpha-SRC-1 interactions using bioluminescent resonance energy
      transfer.
AB  - Bioluminescent Resonance Energy Transfer is a naturally occurring phenomenon that
      can be exploited to explore protein-protein interactions in real-time in intact
      cells and cellular extracts. It detects energy transferred between a
      bioluminescent donor enzyme (Renilla luciferase) fusion protein and a fluorescent
      (GFP(2), a mutant of Green Fluorescent Protein) acceptor fusion protein. Optimal
      detection of BRET(2) energy transfer relies on the distance and orientation
      generated by the fusion proteins. This chapter describes in detail the BRET(2)
      assay as it is used to examine the physical interaction between the nuclear
      receptor ERalpha and the transcriptional coactivator SRC-1. Description of
      methods include selection of donor and acceptor combinations, fusion construct
      generation and validation, cell culture and transfection, individual fluorescence
      and luminescence detection, BRET(2) detection, and data analysis.

PMID- 19763510
TI  - Detection of proteins sumoylated in vivo and in vitro.
AB  - Small ubiquitin-related modifier (SUMO) is an ubiquitin-like protein that is
      covalently attached to a variety of target proteins. Unlike ubiquitination,
      sumoylation does not target proteins for proteolytic breakdown, but is instead
      involved in regulating multiple protein functional properties including protein
      protein interactions and subcellular targeting, to name a few. Protein
      sumoylation has been particularly well characterized as a regulator of many
      nuclear processes as well as nuclear structure, making the characterization of
      this modification vital for understanding nuclear structure and function.
      Consequently, there has been intense interest in identifying new proteins that
      are targets of this modification and determining what role it plays in regulating
      their functions. This chapter presents methodologies for determining whether a
      particular protein is a substrate of sumoylation, and for identifying the lysine
      residue(s) where the modification occurs.

PMID- 19763511
TI  - Identification of alternative transcripts using rapid amplification of cDNA ends
      (RACE).
AB  - Many organisms, including humans, have many more proteins than are actually coded
      for by their genes. This discrepancy is partially explained by the existence of
      alternative transcripts produced by the same gene. Multiple isoforms of the same
      gene sometimes perform completely different functions, and as such, knowing the
      sequence of one of the transcripts is not enough. Rapid Amplification of cDNA
      Ends (RACE) provides an inexpensive and powerful tool to quickly identify
      alternative transcripts of a gene when the partial or complete sequence of only
      one transcript is known. In the following sections, we outline details for rapid
      amplification of 5' and 3' cDNA ends using the "New Race" technique.

PMID- 19763512
TI  - Use of laser capture microdissection in studying hormone-dependent diseases:
      endometriosis.
AB  - Endometriosis, a common gynecological disorder responsible for infertility and
      pelvic pain, is defined as the presence of endometrial glands and stroma within
      extra-uterine sites. Gene expression studies performed on endometriotic tissue
      homogenates have yielded results reflecting mRNA abundance in a mixture of cell
      types (including epithelial cells, stromal cells, fibrotic tissue, and muscle
      tissue). Therefore, a method for quantifying gene expression separately in
      individual cell populations is essential for identifying genetic markers. Laser
      capture microdissection is a technique for obtaining pure populations of cells
      from heterogeneous tissues. This chapter provides methods to obtain high-quality
      RNA suitable for a variety of different down stream applications from frozen
      endometrial and endometriotic tissues for laser capture microdissection, using
      the Arcturus PixCell II system.

PMID- 19763513
TI  - Reporter mice for the study of intracellular receptor activity.
AB  - During the past decade the remarkable progress in molecular genetics and the
      possibility to engineer cells to express genes reporting on the activity of
      specific promoters has produced major changes in biological research. The
      description and validation of reporter mice for non-invasive assessment of
      biological and biochemical processes in living subjects and the results obtained
      with the models reporting on the activity of estrogen and peroxisome proliferator
      receptors clearly showed that such technologies have the potential to enhance our
      understanding of disease and drug activity. Although reporter-gene technology is
      in its infancy, reporter animals already represent a valuable tool for biomedical
      investigation. The present chapter aims at critically illustrating the
      methodology to be applied when dealing with reporter systems and in vivo imaging.

PMID- 19763514
TI  - Real-time non-invasive imaging of ES cell-derived insulin producing cells.
AB  - ES cells are a potential source for insulin producing cells (IPCs). However, two
      major handicaps are establishing reliable differentiation protocols and the lack
      of imaging techniques that allow monitoring of these cells post-transplantation.
      Here, we describe a new approach for monitoring the in vitro differentiation and
      real-time, non-invasive imaging of ES cell-derived IPCs in vivo. ES cells were
      molecularly engineered so that the rat insulin promoter (RIP) driven luciferase
      (Luc) expression was specifically turned on and up regulated following their
      differentiation into IPCs. The rationale underlying this approach is that the
      transcriptional activation of RIP leads to Luc expression in IPCs providing an
      extremely sensitive reporter for monitoring the earliest differentiation events
      in real-time both in vitro and in vivo.

PMID- 19763515
TI  - Transgenic mouse technology: principles and methods.
AB  - Introduction of foreign DNA into the mouse germ line is considered a major
      technical advancement in the fields of developmental biology and genetics. This
      technology now referred to as transgenic mouse technology has revolutionized
      virtually all fields of biology and provided new genetic approaches to model many
      human diseases in a whole animal context. Several hundreds of transgenic lines
      with expression of foreign genes specifically targeted to desired
      organelles/cells/tissues have been characterized. Further, the ability to spatio
      temporally inactivate or activate gene expression in vivo using the "Cre-lox"
      technology has recently emerged as a powerful approach to understand various
      developmental processes including those relevant to molecular endocrinology. In
      this chapter, we will discuss the principles of transgenic mouse technology, and
      describe detailed methodology standardized at our institute.

PMID- 19763516
TI  - Breast tumor-initiating cells isolated from patient core biopsies for study of
      hormone action.
AB  - In recent years, evidence has emerged supporting the hypothesis that cancer is a
      stem cell disease. The cancer stem cell field was led by the discovery of
      leukemia stem cells (Tan, B.T., Park, C.Y., Ailles, L.E., and Weissman, I.L.
      (2006) The cancer stem cell hypothesis: a work in progress. Laboratory
      Investigation. 86, 1203-1207), and within the past few years cancer stem cells
      have been isolated from a number of solid tumor including those of breast and
      brain cancer among others (Al-Hajj M., Wicha M.S., Benito-Hernandez A., Morrison,
      S.J., and Clarke, M.F. (2003) Prospective identification of tumorigenic breast
      cancer cells. Proc. Natl. Acad. Sci. USA 100, 3983-3988; Singh, S.K., Clarke,
      I.D., Terasaki, M., Bonn, V.E., Hawkins, C., Squire, J., and Dirks, P.B. (2003)
      Identification of a Cancer Stem Cell in Human Brain Tumors. Cancer Research. 63,
      5821-5828). Cancer stem cells exhibit far different properties than established
      cells lines such as relative quiescence, multidrug resistance, and multipotency
      (Clarke, M.F., Dick, J.E., Dirks, P.B., Eaves, C.J., Jamieson, C.H.M., Jones,
      D.L., Visvader, J., Weissman, I.L., and Wahl, G.M. (2006) Cancer Stem Cells
      Perspectives on Current Status and Future Directions: AACR Workshop on Cancer
      Stem Cells. Cancer Research. 66, 9339-9344). In addition, our laboratory has
      demonstrated that breast cancer stem cells exhibit a strong metastatic phenotype
      when passaged in mice. Since stem cells exhibit these somewhat unique properties,
      it will be important for endocrinologists to evaluate hormonal action in these
      precursor cells for a more thorough understanding of cancer biology and
      development of more effective treatment modalities. A relatively easy and low
      cost method was developed to isolate breast cancer stem cells from primary needle
      biopsies taken from patients diagnosed with primary invasive ductal carcinoma
      during the routine care of patients with consent and IRB approval. Fresh needle
      biopsies (2-3 biopsies at 2 cm in length) were enzymatically dissociated in a
      collagenase (300 U/ml)/hyaluronidase (100 U/ml) solution followed by sequential
      filtration. Single cell suspensions were cultured on ultra low attachment plastic
      flasks in defined medium and formed non-adherent tumorspheres. The tumorspheres
      exhibited surface marker expression of CD44(+)/CD24(low/-)/ESA(+), previously
      defined as a "breast cancer stem cell" phenotype by Al Hajj et al. (Al-Hajj M.,
      Wicha M.S., Benito-Hernandez A., Morrison, S.J., and Clarke, M.F. (2003)
      Prospective identification of tumorigenic breast cancer cells.

PMID- 19763517
TI  - Markers of oxidative stress and sperm chromatin integrity.
AB  - Oxidative stress (OS) is an imbalance between the amount of reactive oxygen
      species (ROS) produced and the ability of the antioxidants to scavenge these. OS
      has been established as a major etiological cause of male infertility. High
      levels of ROS are harmful and cause damage to sperm nuclear DNA. Evaluation of OS
      related damage to spermatozoa is therefore highly relevant in assisted
      reproductive techniques (ART) such as intracytoplasmic sperm injection (ICSI).
      ICSI is an effective therapy for severe male factor infertility that bypasses the
      majority of reproductive tract deficiencies. Despite the controversial findings
      in the existing literature, there is now enough evidence to show that sperm DNA
      damage is detrimental to reproductive outcomes. In addition to impairment of
      fertility, such damage might increase the transmission of genetic diseases to the
      offspring. Standardization of protocols to assess ROS, antioxidant status, and
      DNA damage is very important for implementation of these tests in clinical
      practice. Estimation of seminal ROS levels and extent of sperm DNA damage,
      especially in an infertile male, may help develop new therapeutic strategies and
      improve the success of ART.

PMID- 19763518
TI  - Planning and executing a genome wide association study (GWAS).
AB  - In recent years, genome-wide association approaches have proven a powerful and
      successful strategy to identify genetic contributors to complex traits, including
      a number of endocrine disorders. Their success has meant that genome wide
      association studies (GWAS) are fast becoming the default study design for
      discovery of new genetic variants that influence a clinical trait or phenotype.
      This chapter focuses on a number of key elements that require consideration for
      the successful conduct of a GWAS. Although many of the considerations are common
      to any genetic study, the greater cost, extreme multiple testing, and greater
      openness to data sharing require specific awareness and planning by
      investigators. In the section on designing a GWAS, we reflect on ethical
      considerations, study design, selection of phenotype/s, power considerations,
      sample tracking and storage issues, and genotyping product selection. During
      execution, important considerations include DNA quantity and preparation,
      genotyping methods, quality control checks of genotype data, in silico genotyping
      (imputation), tests of association, and replication of association signals.
      Although the field of human genetics is rapidly evolving, recent experiences can
      help guide an investigator in making practical and methodological choices that
      will eventually determine the overall quality of GWAS results. Given the
      investment to recruit patient populations or cohorts that are powered for a GWAS,
      and the still substantial costs associated with genotyping, it is helpful to be
      aware of these aspects to maximize the likelihood of success, especially where
      there is an opportunity for implementing them prospectively.

PMID- 19763519
TI  - [Ulcers following therapy with hydroxyurea. Three case reports and review of the
      literature].
AB  - Hydroxyurea is frequently used for therapy of myeloproliferative disorders. One
      cutaneous side-effect is painful, therapy-resistant ulcers which have bizarre
      configurations and occur at atypical sites for venous ulcers. Improvement or
      healing often first occurs when hydroxyurea is discontinued. We report on one
      patient with essential thrombocythemia and two with polycythemia vera, who
      developed such ulcers during hydroxyurea therapy. In one case, the ulcers
      developed shortly after hydroxyurea was started. In addition we give a short
      overview of the current literature.

PMID- 19763520
TI  - [Lightning strike to a vehicle causing acute acoustic trauma].
AB  - The cochlea and vestibular organ is often affected in lightning strikes. A
      lightning strike to a motor vehicle with cochlear injury has not been described
      hitherto in the literature. We report the case of a 44-year-old male patient with
      sensorineural hearing loss and tinnitus after his car was struck by lightning.
      While hearing loss recovered using intravenous therapy, tinnitus persisted 6
      months after the lightning strike. Cochlear injuries as an acute acoustic trauma
      have to be considered in lightning strikes and can occur when a car is struck by
      lightning.

PMID- 19763521
TI  - [Computer-assisted surgery of the frontal skull base].
AB  - The procedure of instrument navigation has been an established one since its
      introduction in ENT by Schloendorff. It facilitates better intraoperative
      orientation. The opto-electric and electromagnetic procedures are sophisticated
      principles of intraoperative position recognition. It can be assumed that up to
      30% of all ENT hospitals in Germany have access to navigation systems. These
      systems are used almost exclusively for functional endoscopic sinus surgery
      (FESS). The impact of instrument navigation is estimated by surgeons
      predominantly positively. A navigation system enables a saving of up to 10% in
      terms of operating time. Extended approaches in the frontal skull base appear to
      benefit from the use of navigation support to a high degree. However, scientific
      data are still lacking. The current boundaries of simple instrument navigation in
      the frontal skull base are set by the attainable accuracy of approx. 2 mm and the
      relatively simple representation of the information in planar sectional views.
      Instrument navigation should be used in the frontal skull base as frequently as
      possible, even in less complex procedures. Only in this way can familiarity with
      the system be achieved.

PMID- 19763522
TI  - [Tracheal stents for esophagotracheal fistula in laryngectomy patients. Safe
      fixation to the tracheostoma].
AB  - BACKGROUND: Postradiotherapy or malignant esophagotracheal fistulas still
      represent a dilemma. In the absence of surgical options attempts are made to
      close the fistula endoscopically by means of esophageal and/or tracheal stents.
      Tracheal stent placement in laryngectomy patients with terminal stomas is
      particularly problematic due to the risk of stent dislocation during cannula
      replacement PATIENTS AND METHODS: Six laryngectomy patients with high
      esophagotracheal fistulas were each fitted with a coated Ultraflex stent (Boston
      Scientific, Watertown/MA, US). Following skin undermining, the stents were fixed
      to the tracheostoma with interrupted sutures and the skin flaps attached to the
      stent with a second row of sutures. RESULTS: Fistulas could be completely closed
      in all patients and there were no cases of stent dislocation. Cannula replacement
      was unproblematic. CONCLUSIONS: Suture fixation of tracheal stents is a viable
      procedure even for patients with esophagotracheal fistulas and terminal
      tracheostomy following laryngectomy.

PMID- 19763523
TI  - [CO2-laser-assisted de-epithelialization of perforation margins of persistent
      tympanic membrane perforations. An alternative to conventional surgical
      procedures].
AB  - INTRODUCTION: The standard treatment of persistent eardrum perforation is
      conventional surgical closure using myringoplasty or a tympanoplasty type I. In
      this study the valence of a modified, CO(2)-laser-assisted de-epithelialization
      of perforation margins was investigated. MATERIAL AND METHODS: A total of 44
      patients with mesotympanal eardrum perforation (diameter 1-5 mm) were included in
      a partially retrospective and partially prospective study. The genesis of the
      eardrum perforations was partially traumatic or the eardrum did not heal after
      spontaneous perforation caused by an acute otitis media or after surgery. The
      procedure was performed under topical anaesthesia. Focussed, adjacent, single
      CO(2) laser pulses (1 watt, 0.05 s) were applied with the laser otoscope Otoscan
      (Lumenis, Yokneam, Israel) along the edge of the perforation until complete de
      epithelialization. This was done to stimulate growth. Closure of eardrum
      perforation was monitored using an ear microscope and if this treatment was not
      successful after three attempts conventional surgical therapy was suggested.
      RESULTS: Complete eardrum closure occurred in 27 cases (61%), 17 patients (39%)
      had a residual perforation, of which 9 experienced a significant reduction of the
      perforation. There were no complications during and after the treatment.
      CONCLUSION: A closure rate of at least 61% (27/44) can be expected with a CO(2)
      laser-assisted de-epithelialization of the perforation margins. This procedure
      can be performed under topical anaesthesia and is an economic, painless and
      facile alternative to conventional surgical treatment.

PMID- 19763524
TI  - Post-translationally modified T cell epitopes: immune recognition and
      immunotherapy.
AB  - The functionality of proteins is greatly extended by a diverse array of post
      translational modifications (PTMs), many of which are recognized by the immune
      system. Notably, a significant proportion of peptides presented to T cells by the
      major histocompatibility complex in vivo are post-translationally modified. Since
      the cellular mechanisms that introduce and control protein modifications can
      differ between health and disease, the associated changes in antigen presentation
      have the potential to alter immune responses. A number of such situations have
      been implicated with infection, inflammation, autoimmune disease, and cancer, and
      the investigation of PTMs that affect antigen recognition has provided insight in
      disease progression as well as raising prospects for novel approaches in
      immunotherapy.

PMID- 19763525
TI  - Disease mutations in the "head" domain of the extra-sarcomeric protein desmin
      distinctly alter its assembly and network-forming properties.
AB  - The intermediate filament protein desmin generates an extra-sarcomeric network in
      myocytes. Mutations in the desmin gene cause myofibrillar myopathy characterized
      by desmin-positive aggregates and myofibrillar dissolution. Past analysis
      revealed that the non-alpha-helical amino-terminal "head" domain of desmin is a
      vital coordinator of protein assembly. We have now characterized assembly and
      network-forming properties of five recently discovered myopathy-causing mutations
      residing in this domain. In vitro analyses with recombinant proteins show that
      two mutant variants residing in a conserved nonapeptide motif "SSYRRTFGG"
      Ser13Phe and Arg16Cys-interfere with assembly by forming filamentous aggregates.
      Consistent with in vitro data, both mutant proteins are unable to generate a bona
      fide filament system in cells lacking an intermediate filament cytoskeleton. In
      cells expressing vimentin or desmin, both mutants firstly fail to integrate into
      the endogenous filament network and secondly severely affect its cellular
      localization. The other three mutations-Ser2Iso, Ser46Phe, and Ser46Tyr-influence
      in vitro filament properties less severely, but in vivo, Ser46Phe and Ser46Tyr
      impair de novo filament formation. These effects of the "head" mutant proteins on
      endogenous intermediate filament system and their competition for binding to
      cellular anchoring structures might explain part of the molecular mechanism that
      causes disease.

PMID- 19763526
TI  - Lysosomal ceramide mediates gemcitabine-induced death of glioma cells.
AB  - Acid sphingomyelinase-induced ceramide release has been shown by many studies to
      induce apoptosis in response to various stimuli. However, the mechanisms of acid
      sphingomyelinase/ceramide-mediated death signaling following treatment with
      chemotherapeutic drugs have not been fully elucidated thus far. The present study
      demonstrates that treatment of glioma cells with clinically achievable doses of
      gemcitabine results in acid sphingomyelinase activation, lysosomal accumulation
      of ceramide, cathepsin D activation, Bax insertion into the mitochondria, and
      cell death. Pharmacological inhibition or genetic deficiency of acid
      sphingomyelinase prevented these events while overexpression of the enzyme
      sensitized cells to gemcitabine. Likewise, inhibitors of lysosomal functions also
      prevent gemcitabine-induced cell death. Our data indicate a critical role of the
      acid sphingomyelinase/ceramide system for gemcitabine-induced signaling and
      suggest that lysosomal ceramide accumulation mediates cell death induced by a
      chemotherapeutic drug.

PMID- 19763527
TI  - Evolutionary plant physiology: Charles Darwin's forgotten synthesis.
AB  - Charles Darwin dedicated more than 20 years of his life to a variety of
      investigations on higher plants (angiosperms). It has been implicitly assumed
      that these studies in the fields of descriptive botany and experimental plant
      physiology were carried out to corroborate his principle of descent with
      modification. However, Darwin's son Francis, who was a professional plant
      biologist, pointed out that the interests of his father were both of a
      physiological and an evolutionary nature. In this article, we describe Darwin's
      work on the physiology of higher plants from a modern perspective, with reference
      to the following topics: circumnutations, tropisms and the endogenous oscillator
      model; the evolutionary patterns of auxin action; the root-brain hypothesis;
      phloem structure and photosynthesis research; endosymbioses and growth-promoting
      bacteria; photomorphogenesis and phenotypic plasticity; basal metabolic rate, the
      Pfeffer-Kleiber relationship and metabolic optimality theory with respect to
      adaptive evolution; and developmental constraints versus functional equivalence
      in relationship to directional natural selection. Based on a review of these
      various fields of inquiry, we deduce the existence of a Darwinian (evolutionary)
      approach to plant physiology and define this emerging scientific discipline as
      the experimental study and theoretical analysis of the functions of green,
      sessile organisms from a phylogenetic perspective.

PMID- 19763528
TI  - [Car driving ability of patients with frontotemporal lobar degeneration and
      Alzheimer's disease].
AB  - BACKGROUND: The following study presents in detail newly occurring changes in
      driving ability of patients with Alzheimer's disease (AD) and dementia due to
      frontotemporal lobar degeneration (FTLD). PATIENTS AND METHODS: The caregivers of
      30 patients with FTLD (20 with FTD, 10 with SD) and 26 matched patients with AD
      were interviewed on potential alterations in driving ability using a standardized
      questionnaire. RESULTS: Of the patients 90% with FTLD and 58% with AD showed
      changes in driving behavior. In AD the predominating alteration was an unsteady
      style of driving with increased lack of orientation. Patients with FTLD presented
      an aggressive and risky style of driving including various traffic rule
      violations. Significant differences between the two groups were observed
      regarding speeding, disregarding red traffic lights, inappropriate behavior and
      driving despite being forbidden by the family Of the patients with FTLD 37% were
      responsible for at least one accident since disease onset in comparison to 19% of
      patients with AD (p=0.24). Most patients with AD showed a reasonable attitude to
      their change in driving behavior, however the majority of patients with FTLD
      showed a lack of understanding for the fact that their style of driving presented
      a potential risk and did not accept the need to stop driving (p=0.023).
      CONCLUSION: Patients with FTLD should cease driving as soon as possible in the
      course of the disease. With patients suffering from mild AD an individual
      assessment should be made.

PMID- 19763529
TI  - [Fragile X-associated tremor/ataxia syndrome].
AB  - Fragile X-associated tremor/ataxia syndrome (FXTAS) is a recently characterized
      adult onset neurodegenerative disorder affecting both male and female
      (male>female) carriers of premutation CGG repeat expansions of the FMR1 gene.
      Onset typically occurs after the age of 50 years with a lifetime risk of FXTAS in
      males of about 1 in 3,000-6,000. Core features include progressive gait ataxia
      and cerebellar tremor with associated features of cognitive deficits, peripheral
      neuropathy and dysautonomia. The diagnosis of FXTAS is established based on
      clinical presentation, cerebral imaging and genetic testing. Due to the still low
      level of awareness of FXTAS and its variable clinical picture FXTAS is
      substantially underdiagnosed. However, confirming the diagnosis is essential for
      genetic counseling of the patients as the offspring are at risk for fragile X
      syndrome, premature ovarian insufficiency (POI) or FXTAS. Furthermore, many
      features of FXTAS can be treated symptomatically.

PMID- 19763530
TI  - [Repetitive peripheral magnetic stimulation.  Treatment option for spasticity?].
AB  - BACKGROUND: In an open study the effect of repetitive peripheral magnetic
      stimulation (RPMS) on the spastic talipes equinus of various origins, degree and
      duration was evaluated in 53 children and adolescents. STUDY DESIGN AND METHODS:
      Clinical and electrophysiological investigations were designed to measure the
      RMPS effect on the spasticity and the functional capabilities of the spastic
      talipes equines. Moreover, the duration of the effect of one RPMS session should
      be established. The magnetic stimulation comprising 10 series of 10 s duration
      was applied over the first sacral radix using a frequency of 20 Hz and a 1.2-fold
      intensity above the motoric threshold. RESULTS: The RPMS significantly reduced
      the tonus of the spastic talipes equines and this effect lasted for 1 week. No
      significant changes of electrophysiological parameters measuring the F-wave, H
      reflex und ASR tendon reflex could be observed. CONCLUSION: The RPMS could prove
      to be an effective option for the treatment of spasticity. However, this method
      needs further evaluation by evidence-based studies.

PMID- 19763533
TI  - Wheat stripe rust resistance genes Yr5 and Yr7 are allelic.
AB  - Stripe rust is one of the most destructive diseases of wheat. Breeding for
      resistance is the most economical and environmentally acceptable means to control
      stripe rust. Genetic studies on resistance sources are very important. Previous
      inheritance studies on Triticum aestivum subsp. spelta cv. album and wheat
      cultivar Lee showed that each possessed a single dominant gene for stripe rust
      resistance, i.e., Yr5 and Yr7, respectively. Both were located on the long arm of
      chromosome 2B, but due to the complexities caused by genetic background effects
      there was no clear evidence on the allelism or linkage status of these genes. Our
      study, involving an intercross of Avocet S near-isogenic lines possessing the
      genes, provided clear evidence for allelism or extremely close linkage of Yr5 and
      Yr7 based on phenotypic and molecular studies.

PMID- 19763534
TI  - Identification of quantitative trait loci for resistance to shoot fly in sorghum
      [Sorghum bicolor (L.) Moench].
AB  - The shoot fly is one of the most destructive insect pests of sorghum at the
      seedling stage. Deployment of cultivars with improved shoot fly resistance would
      be facilitated by the use of molecular markers linked to QTL. The objective of
      this study was to dissect the genetic basis of resistance into QTL, using
      replicated phenotypic data sets obtained from four test environments, and a 162
      microsatellite marker-based linkage map constructed using 168 RILs of the cross
      296B (susceptible) x IS18551 (resistant). Considering five component traits and
      four environments, a total of 29 QTL were detected by multiple QTL mapping (MQM)
      viz., four each for leaf glossiness and seedling vigor, seven for oviposition,
      six for deadhearts, two for adaxial trichome density and six for abaxial trichome
      density. The LOD and R (2) (%) values of QTL ranged from 2.6 to 15.0 and 5.0 to
      33%, respectively. For most of the QTL, IS18551 contributed resistance alleles;
      however, at six QTL, alleles from 296B also contributed to resistance. QTL of the
      related component traits were co-localized, suggesting pleiotropy or tight
      linkage of genes. The new morphological marker Trit for trichome type was
      associated with the major QTL for component traits of resistance. Interestingly,
      QTL identified in this study correspond to QTL/genes for insect resistance at the
      syntenic maize genomic regions, suggesting the conservation of insect resistance
      loci between these crops. For majority of the QTL, possible candidate genes lie
      within or very near the ascribed confidence intervals in sorghum. Finally, the
      QTL identified in the study should provide a foundation for marker-assisted
      selection (MAS) programs for improving shoot fly resistance in sorghum.

PMID- 19763535
TI  - Heritability and genetic correlations of insulin resistance and component
      phenotypes in Asian Indian families using a multivariate analysis.
AB  - AIMS/HYPOTHESIS: Insulin resistance and related metabolic disturbances are more
      common among Asian Indians than European whites. Little is known about the
      heritability of insulin resistance traits in Asian Indians. Our objective was to
      estimate heritabilities and genetic correlations in Asian Indian families.
      METHODS: Phenotypic data were assembled for 181 UK Asian Indian probands with
      premature CHD, and their 1,454 first-, second- and third-degree relatives. We
      calculated (narrow-sense) heritabilities and genetic correlations for insulin
      resistance traits, and common environmental effects using all study participants
      and a multivariate model. The analysis was repeated in a subsample consisting of
      individuals not on drug therapy. RESULTS: Heritability estimates (SE) for
      individuals not on drug therapy were: BMI 0.31 (0.04), WHR 0.27 (0.04), systolic
      BP 0.29 (0.03), triacylglycerol 0.40 (0.04), HDL-cholesterol 0.53 (0.04), glucose
      0.37 (0.03), HOMA of insulin resistance (HOMA-IR) 0.22 (0.04), and HbA(1c) 0.60
      (0.04). We observed many significant genetic correlations between the traits, in
      particular between HOMA-IR and BMI. Heritability estimates were lower for all
      phenotypes when analysed among all participants. CONCLUSIONS/INTERPRETATION:
      Genetic factors contribute to a significant proportion of the total variance in
      insulin resistance and related metabolic disturbances in Asian Indian CHD
      families.

PMID- 19763536
TI  - [Cervical spine osteoblastoma in children: Selective diagnostics as the basis for
      effective surgical management].
AB  - Expansively growing cervical spine osteoblastomas are rare but can cause severe
      neurological damage as a result of their anatomical relationship to nerve
      structures. Also, cerebral vessels, especially the vertebral artery in its
      transvertebral position, are often covered by tumor tissue. In complete resection
      of the tumor, it is sometimes possible to retain the affected vessel. In addition
      to conventional radiographic diagnostics, computed tomography, and magnetic
      resonance imaging, angiography and Doppler sonography of the intracranial
      arteries executed in parallel can provide evidence of the dimension of the
      neurological deficit to be expected during resection. This case report describes
      the staged diagnostic procedure and successful complete resection, retaining the
      affected vertebral artery, of an osteoblastoma of the 5th cervical body with
      massive intraspinal expansion in an 11-year-old child.

PMID- 19763537
TI  - Dilutional acidosis: where do the protons come from?
AB  - PURPOSE: To investigate the mechanism of acidosis developing after saline
      infusion (dilutional acidosis or hyperchloremic acidosis). METHODS: We simulated
      normal extracellular fluid dilution by infusing distilled water, normal saline
      and lactated Ringer's solution. Simulations were performed either in a closed
      system or in a system open to alveolar gases using software based on the standard
      laws of mass action and mass conservation. In vitro experiments diluting human
      plasma were performed to validate the model. RESULTS: In our computerized model
      with constant pKs, diluting extracellular fluid modeled as a closed system with
      distilled water, normal saline or lactated Ringer's solution is not associated
      with any pH modification, since all its determinants (strong ion difference,
      CO(2) content and weak acid concentration) decrease at the same degree,
      maintaining their relative proportions unchanged. Experimental data confirmed the
      simulation results for normal saline and lactated Ringer's solution, whereas
      distilled water dilution caused pH to increase. This is due to the increase of
      carbonic pK induced by the dramatic decrease of ionic strength. Acidosis
      developed only when the system was open to gases due to the increased CO(2)
      content, both in its dissociated (bicarbonate) and undissociated form (dissolved
      CO(2)). CONCLUSIONS: The increase in proton concentration observed after dilution
      of the extracellular system derives from the reaction of CO(2) hydration, which
      occurs only when the system is open to the gases. Both Stewart's approach and the
      traditional approach may account for these results.

PMID- 19763538
TI  - Semimembranosus tendon viewed through an isolated medial meniscus capsular
      avulsion: a case report.
AB  - The semimembranosus is a key component of the complex anatomy of the
      posteromedial knee. Its multiple distal insertions are intimately associated with
      the posterior capsule, medial meniscus, and posterior oblique ligament.
      Visualization of the semimembranosus is possible during arthroscopy when a
      significant posteromedial capsular injury is present. This typically occurs only
      in the setting of significant trauma, with associated injury to the other
      posteromedial knee structures. We present a case of an isolated medial meniscus
      capsular avulsion, with minimal trauma, in which the semimembranosus tendon is
      clearly visualized during arthroscopic meniscal repair.

PMID- 19763539
TI  - Biomechanical evaluation of using one hamstrings tendon   for ACL reconstruction:
      a human cadaveric study.
AB  - Harvesting both the semitendinosus and gracilis tendons for anterior cruciate
      ligament (ACL) reconstruction has a negative impact on muscle strength as well as
      knee function and stability. With a new "All-inside" technique, using only one
      hamstrings tendon (semitendinosus or gracilis) is possible because of a reduction
      in length requirements. The research question of this in vitro study was whether
      the use of only one hamstrings tendon (semitendinosus or gracilis) could restore
      knee kinematics and in situ force in the ACL to the level of an intact knee.Ten
      human cadaveric knees were tested in the following conditions: (1) intact, (2)
      ACL-deficient, and (3) ACL reconstruction with the "All-inside" technique using
      the (a) single semitendinosus tendon graft, or (b) single gracilis tendon graft.
      Using a robotic testing system, external loads, i.e. (1) an anterior tibial load
      of 134-N and (2) combined rotatory loads of 10-Nm valgus and 5-Nm internal tibial
      torques, were applied. The multiple degrees of freedom knee kinematics and the in
      situ forces in the ACL and ACL grafts were determined. In response to a 134-N
      anterior tibial load, the use of either graft could restore anterior tibial
      translation to within 1.3 mm of the intact knee. The in situ forces in the two
      grafts were not significantly different from those of the intact ACL. Under the
      combined rotatory loads, both grafts could restore knee kinematics as well as the
      in situ force in the grafts to the level of the intact ACL. The "All-inside"
      technique using either the semitendinosus or gracilis tendon for ACL
      reconstruction could satisfactorily restore time-zero knee kinematics and the in
      situ forces in either graft to those for the intact ACL, supporting clinical
      findings.

PMID- 19763540
TI  - Autologous chondrocyte implantation in the knee using fibrin.
AB  - Autologous chondrocyte implantation (ACI) is widely used to treat symptomatic
      articular cartilage injury of the knee. Fibrin ACI is a new tissue-engineering
      technique for the treatment of full-thickness articular cartilage defects, in
      which autologous chondrocytes are inserted into a three-dimensional scaffold
      provided by fibrin gel. The objective of this study is to document and compare
      mean changes in overall clinical scores at both baseline and follow-up. Fibrin
      ACI was used to treat deep cartilage defects of the femoral condyle in 30
      patients. There were 24 men and 6 women with a median age of 35 years (range 15
      55) and with a mean defect size of 5.8 cm(2) (range 2.3-12). Clinical and
      functional knee evaluations were performed using different scoring systems, MRI
      was performed 24 months postoperatively, and arthroscopy was performed 12 months
      postoperatively. All patients achieved clinical and functional status
      improvements following surgery (P < 0.01). The mean scores of the Henderson
      classification (MRI evaluation) significantly improved from 14.4 to 7 (P =
      0.001), and no graft-associated complications were noted. Arthroscopic
      assessments performed 12 months postoperatively produced nearly normal (grade II)
      International Cartilage Repair Society scores in 8 of the 10 study patients.
      Fibrin ACI offers the advantages of technical simplicity, minimal invasiveness, a
      short surgery time, and easier access to difficult sites than classical ACI.
      Based on the findings of this clinical pilot study, we conclude that fibrin ACI
      offers a reliable means of treating articular cartilage defects of the knee.

PMID- 19763541
TI  - Minimally invasive unicompartmental knee replacement: retrospective clinical and
      radiographic evaluation of 83 patients.
AB  - We performed a retrospective clinical and radiographic evaluation of 83
      nonconsecutive patients operated in our institute between February 1996 and March
      2003 with a mean follow-up of 60 months to assess the efficiency of
      unicompartmental knee replacement (UKR) performed with a minimally invasive
      technique. The aim of this study was to correlate the clinical outcome with the
      pre- and post-operative alignment and with implant positioning on coronal and
      sagittal plane. Eighty-three nonconsecutive patients (60 males, 23 females)
      underwent cemented UKR (De Puy Preservation Uni with all-poly tibial component),
      for both medial OA (80 patients) and AVN of the medial femoral condyle (3
      patients). All patients were available at final follow-up evaluation, and they
      all presented an evident varus alignment at pre-operative clinical and
      radiographic evaluation. At radiographic measurement, we considered a knee with
      femoro-tibial angle (FTA) > 175 degrees as varus knee, 170 degrees < FTA < 175
      degrees as normal knee and a knee with a FTA < 170 degrees as a valgus knee.
      Moreover, we considered a tibial plateau angle (TPA) > 90 degrees for valgus knee
      and a TPA < 90 degrees for varus knee. According to Hospital for Special Surgery
      (HSS) scoring system, at a mean follow-up of 60 months, 61 (74%) cases were
      excellent (100-85 points), 15 (18%) cases were good (84-70 points) and 7 cases
      (8%) had fair results (<70 points). In our series, patients with an excellent
      clinical result presented a mean varus deformity of 7.2 degrees (3.6 degrees-10.8
      degrees) pre-operatively. According to literature, we demonstrated that a small
      amount of undercorrection with a small amount of residual varus deformity of 3
      degrees-5 degrees is the goal to be reached in order to avoid both rapid
      degeneration of the nonreplaced compartment and the premature loosening of the
      replaced compartment. We performed a mean axial correction of 5 degrees (SD 3.9
      degrees), leaving a mean axial varus deformity of 2.2 degrees in the excellent
      group. In our series, the group with excellent results also showed a post
      operative PTS of 7 degrees (2.4 degrees-11.6 degrees), while mean pre-operative
      PTS was 6.5 degrees (2.7 degrees-10.3 degrees). In this study, results have shown
      that minimally invasive UKR producing a small amount of varus undercorrection in
      selected patients with medial tibio-femoral osteoarthritis or moderate avascular
      necrosis of the medial femoral condyle provides excellent clinical and functional
      results. Overcorrection of varus malalignment with a UKR may produce both rapid
      degeneration of the lateral tibio-femoral compartment and the early failure of
      the replaced compartment.

PMID- 19763542
TI  - Effects of 4-pyridine aldoxime on nerve agent-inhibited acetylcholinesterase
      activity in guinea pigs.
AB  - Methoxime (MMB-4) is a leading candidate oxime acetylcholinesterase (AChE)
      reactivator to replace pralidoxime (2-PAM) for therapeutic treatment of nerve
      agent intoxication. 4-Pyridine aldoxime (4-PA) is a synthetic starting material,
      a breakdown product, and a probable metabolite of MMB-4. There is a possibility
      that 4-PA may adversely interact with the nerve agent, thereby affecting nerve
      agent toxicity and biological AChE activity. This study evaluated the effects of
      4-PA on sarin (GB)-, cyclosarin (GF)-, and VX-induced toxicity and AChE activity
      in blood, brain, and peripheral tissues of guinea pigs. Animals were pretreated
      with atropine methyl nitrate (1.0 mg/kg, im) 15 min prior to subcutaneous
      administration with 1.0 x LD(50) of GB, GF, or VX and then treated 15 min after
      the administration of nerve agents with 4-PA (3.5, 7.0, or 14.0 mg/kg, im). The
      dose-response effects of 4-PA alone were also examined. Toxic signs and lethality
      were monitored, blood and tissues were collected, and AChE activities were
      determined at 60 min after nerve agent administration. Under the condition of
      this study, all animals exposed to nerve agents exhibited some degree of toxic
      signs such as salivation, lacrimation, rhinorrhea, and convulsions. 4-PA at the
      three doses tested neither induced toxic signs nor altered the toxicity of GB,
      GF, or VX at the 1.0 x LD(50) exposure dose. Additionally, it did not modify the
      AChE activity in blood, brain, and peripheral tissues by itself or affect the
      AChE activity inhibited by a 1.0 x LD(50) dose of these three nerve agents in
      guinea pigs.

PMID- 19763543
TI  - Effects of synthetic para-nonylphenol isomers administered chronically throughout
      pregnancy and lactation on reproductive system of mouse pups.
AB  - The aim of this study was to analyze the effects of synthetic para-nonylphenol
      isomers administered chronically throughout pregnancy and lactation on the
      reproductive system of mouse pups. The two synthetic isomers used in this study
      showed higher (3E22NP) or lower (44NP) estrogen receptor (ER) binding activity on
      in vitro yeast assay than a commercial NP (NPmix). Female mice were implanted
      with a tube filled with one of three NPs and estradiol-17 beta (E2) before
      mating. The tube was kept in the mice throughout pregnancy and lactation period,
      until their pups had weaned at 28 days of age (PND 28). The data indicated that
      in males, NPs decreased body weight in some dose groups on PND28 and increased
      weights of testes and epididymides. However, the rate of seminiferous tubules
      having elongate spermatids (steps 10-16) decreased significantly in NPs and E2
      treated groups, except for the 44NP groups. In female mice, NPs and E2 increased
      weights of ovaries, uterus and vagina in the pups in some dose groups on PND 28.
      However, there were no differences in the day of vaginal opening and numbers of
      corpus lutea. The present study demonstrates that the effects of these two
      isomers of NP on the pup reproduction at PND 28 are not quite different, despite
      them showing different levels of ER binding activity using in vitro yeast assay.

PMID- 19763544
TI  - Protective effects of epigallocatechin gallate following 3-nitropropionic acid
      induced brain damage: possible nitric oxide mechanisms.
AB  - INTRODUCTION: The role of oxidative stress has been well known in
      neurodegenerative disorders. 3-Nitropropionic acid (3-NP) is a plant-based
      mycotoxin that produces HD like symptoms in animals. Oxidative stress and nitric
      oxide mechanisms have been recently proposed in the 3-NP-induced neurotoxicity.
      Epigallocatechin gallate (EGCG) is one of the major components of green tea,
      known for its potent antioxidant activity. Besides, neuroprotective effect of
      EGCG has also been suggested in different experimental models. OBJECTIVES: The
      present study has been designed to examine possible effect of EGCG against 3-NP
      induced behavioral, oxidative stress, mitochondrial dysfunction, and striatal
      damage in rats and its possible interaction with nitric oxide modulators.
      MATERIAL AND METHODS: Systemic 3-NP (10 mg/kg) administration for 14 days
      significantly reduced locomotor activity, body weight, grip strength, oxidative
      defense (raised levels of lipid peroxidation, nitrite concentration, depletion of
      antioxidant enzyme), and mitochondrial enzymes activity in striatum, cortex, and
      hippocampal regions of the brain. RESULTS: Fourteen days of EGCG pretreatment
      (10, 20, and 40 mg/kg) significantly attenuated behavioral alterations, oxidative
      damage, mitochondrial complex enzymes dysfunction, and striatal damage in 3-NP
      treated animals. L-arginine (50 mg/kg) pretreatment with sub-effective dose of
      EGCG (20 mg/kg) significantly reversed the protective behavioral, biochemical,
      cellular, and histological effects of EGCG. However, L-NAME (10 mg/kg)
      pretreatment with EGCG (20 mg/kg) significantly potentiated the protective effect
      of EGCG which was significant as compared to their effect per se. CONCLUSION: The
      present study shows that EGCG attenuate 3-NP-induced neurotoxicity, and nitric
      oxide modulation might be involved in its protective action.

PMID- 19763545
TI  - Microwave-assisted sensing of tetracycline using europium-sensitized luminescence
      fibers as probes.
AB  - In this paper, we describe a facile approach--using silicate fibers immobilized
      with Eu(III) ions [Eu(III) fibers] as affinity probes--to rapidly sense
      tetracycline (TC) in complex samples. The fabrication of the Eu(III) fibers is
      straightforward: Simply immerse a silicate fiber into a glass tube containing
      Eu(III) and irradiate with microwaves (power, 900 W) for 30 s. The Eu(III) fibers
      selectively trap TC from aqueous samples via chelation of the beta-diketone
      functional group of TC with the Eu(III) center. Because the Eu(III)-TC complexes
      on the fibers are luminescent, as a result of intermolecular energy transfer from
      the TC moieties to the Eu(III) centers, they can be detected directly using a
      fluorophotometer. To accelerate the sensing process, we also used microwave
      irradiation (for only 15 s) to trap the TC molecules from the sample solutions
      onto the Eu(III) fibers. Furthermore, only a small volume (< 10 microL) of sample
      solution is required for these analyses. This approach allows TC to be detected
      in aqueous samples, with a detection limit of 50 nM.

PMID- 19763546
TI  - The ability of a novel sorptive polymer to determine the freely dissolved
      fraction of polar organic compounds in the presence of fulvic acid or sediment.
AB  - A novel plastic material, poly(ethylene-co-vinyl acetate-co-carbon monoxide)
      (PEVAC), was evaluated as an absorptive passive equilibrium sampler for
      determination of the freely dissolved fraction of seven polar organic
      contaminants (POCs) in the presence of fulvic acid and sediment. The seven
      compounds selected were imidacloprid, carbendazim, metoprolol, atrazin,
      carbamazepine, diazinon and chlorpyrifos, i.e. a mixture of pharmaceuticals and
      pesticides having logarithmic octanol/water partition coefficients (log K(OW))
      ranging from 0.2 to 4.77. The experiments demonstrated that the PEVAC sampler is
      well suited for determination of the freely dissolved fraction of chemicals in
      aquatic environments. Generally, the freely dissolved fraction of the POCs
      decreased with increasing hydrophobicity. However, strong interactions with
      functional groups of the organic matter seemed to dominate the partitioning for
      imidacloprid and carbendazim, having logarithmic dissociation partition
      coefficient log D < 1.47, and for metoprolol, which is positively charged at
      neutral pH.

PMID- 19763547
TI  - Update on analytical methods for toxic pyrrolizidine alkaloids.
AB  - Methods for the determination of toxic pyrrolizidine alkaloids in plants and
      foods are described with emphasis on the important aspects of sample extraction
      and clean-up and the now preferred determination by liquid chromatography-mass
      spectrometry. The efficiencies of different extraction solvents and methods are
      described, as are the methods of reduction of N-oxides. Appropriate liquid
      chromatography-mass spectrometry conditions are tabulated. This concise review is
      intended to guide analysts towards adopting a more unified and reliable approach
      to the analysis of these important toxins.

PMID- 19763548
TI  - ESI-MS/MS library of 1,253 compounds for application in forensic and clinical
      toxicology.
AB  - An electrospray ionization tandem mass spectrometry (ESI-MS/MS) library which
      contains over 5,600 spectra of 1,253 compounds relevant in clinical and forensic
      toxicology has been developed using a hybrid tandem mass spectrometer with a
      linear ion trap. Pure compound solutions-in some cases solutions made of tablets
      were prepared and 1 to 2,000 ng of each compound were injected into the system
      using standard reversed-phase analytical columns with gradient elution. To obtain
      maximum mass spectral information enhanced product ion spectra were acquired with
      positive and/or negative ionization at low, medium, and high collision energies
      and additionally applying collision energy spread. In this mode, all product ions
      generated by the different collision energies are trapped in the linear ion trap
      prior to their detection. The applicability of the library for other types of
      hybrid tandem mass spectrometers with a linear ion trap of the same manufacturer
      as well as a standard triple-quadrupole tandem mass spectrometer has been
      investigated with a selection of compounds. The spectra of the developed library
      can be used to create methods for target analysis, either screening methods or
      quantitative procedures by generating transitions for multiple reaction
      monitoring. For those procedures, suitable transitions and convenient collision
      energies are selected from the library. It also has been utilized to identify
      compounds with a multi target screening approach for clinical and forensic
      toxicology with a standardized and automated system. The novel aspects compared
      to our former library produced with a standard triple-quadrupole mass
      spectrometer are the enlargement of the ESI-MS/MS library and the additional
      acquisition of spectra with collision energy spread.

PMID- 19763549
TI  - Preparation and characterization of enzymatically hydrolyzed prolamins from
      wheat, rye, and barley as references for the immunochemical quantitation of
      partially hydrolyzed gluten.
AB  - Celiac disease (CD) is a permanent gastrointestinal disorder characterized by the
      intolerance to a group of proteins called gluten present in wheat, rye, barley,
      and possibly oats. The only therapy is a strict lifelong gluten-free diet. The
      standard method for gluten determination in foods produced for CD patients is the
      R5-enzyme-linked immunosorbent assay (ELISA) as proposed by the recent Codex
      Alimentarius Draft Revised Standard. This test is based on the determination of
      prolamins, the alcohol-soluble proteins of gluten, and is available as a sandwich
      ELISA for intact proteins and as a competitive ELISA for gluten-derived peptides.
      While the suitability of the sandwich ELISA including a wheat prolamin (gliadin)
      reference for calibration has been shown by various studies and a ring test, the
      competitive ELISA still lacks a convenient reference for the quantitation of
      gluten peptides in fermented cereal foods (e.g., sourdough products, starch
      syrup, malt extracts, beer). Therefore, the aim of the present study was to
      prepare a suitable reference for the quantitation of partially hydrolyzed gluten
      in fermented wheat, rye, and barley products. The prolamin fractions from barley
      (hordein) and rye (secalin) were isolated from corresponding flours by means of a
      modified preparative Osborne fractionation. The prolamin fraction from wheat was
      obtained as reference gliadin from the Prolamin Working Group. The prolamin
      fractions were successively digested by pepsin and trypsin or pepsin and
      chymotrypsin procedures, which have been used for CD-specific toxicity tests on
      cereal storage proteins for many years. The protein/peptide content (N x 5.7) of
      the prolamin fractions and digests, which was the basis for the calculation of
      the gluten content by means of ELISA, varied between 67.1% and 96.0%. The
      prolamin fractions and enzymatic digests were then tested for their response in
      both sandwich and competitive assays. Intact prolamins responded similarly in
      both ELISA showing no important differences between the cereals. In the case of
      digested proteins, however, the sandwich ELISA was considerably less sensitive
      than the competitive ELISA. The former provided approximately 40% and the latter
      70% of the signal intensity obtained with the intact prolamins. Thus, the
      combination of the competitive ELISA and the enzymatic digests of prolamin
      fractions as reference was considered to be an adequate system for the analysis
      of partially hydrolyzed gluten. The limit of detection using a peptic-tryptic
      hordein digest as reference was 2.3 microg prolamin equivalent per milliliter,
      and the limit of quantitation was 6.7 microg prolamin equivalent per milliliter.
      This system was applied for the determination of gluten equivalents in five
      commercial beverages based on fermented cereals.

PMID- 19763550
TI  - Quantification of two urinary metabolites of organophosphorus flame retardants by
      solid-phase extraction and gas chromatography-tandem mass spectrometry.
AB  - Trialkyl esters of phosphoric acid are widely used as flame retardants. The
      corresponding dialkylphosphates are formed as the main metabolites in animal
      experiments. We extended a previously published method for the determination of
      four organophosphorus flame retardant metabolites [bis(2-chloroethyl) phosphate,
      diphenyl phosphate, di-m-cresyl phosphate and di-p-cresyl phosphate] to be able
      to determine di-n-butyl phosphate (DBP) and bis(2-chloropropyl) phosphate (BCPP)
      in human urine samples additionally in one run. After solid-phase extraction,
      derivatization with pentafluorobenzyl bromide and further solid-phase cleanup,
      the extracts were analysed by gas chromatography-tandem mass spectrometry. The
      limits of detection were 0.25 microg/l for both analytes. Interday imprecisions
      were 2-6%. To show the applicability of the method, the internal burden of 25
      persons of the population was determined. Twelve percent of the urine samples
      analysed tested positive for BCPP at concentrations from below the limit of
      detection to 0.85 microg/l; one sample contained 0.26 microg/l DBP.

PMID- 19763551
TI  - Fluorimetric characterization of single-walled carbon nanotubes.
AB  - Single-walled carbon nanotubes (SWCNTs) are a family of structurally related
      artificial nanomaterials with unusual properties and many potential applications.
      Most SWCNTs can emit spectrally narrow near-IR fluorescence at wavelengths that
      are characteristic of their precise diameter and chiral angle. Near-IR
      fluorimetry therefore offers a powerful approach for identifying the structural
      species present in SWCNT samples. Such characterization is increasingly important
      for nanotube production, study, separation, and applications. General-purpose and
      specialized instruments suitable for SWCNT fluorimetric analysis are described,
      and methods for interpreting fluorimetric data to deduce the presence and
      relative abundances of different SWCNT species are presented. Fluorescence
      methods are highly effective for detecting SWCNTs in challenging samples such as
      complex environmental or biological specimens because of the methods' high
      sensitivity and selectivity and the near absence of interfering background
      emission at near-IR wavelengths. Current limitations and future prospects for
      fluorimetric characterization of SWCNTs are discussed.

PMID- 19763552
TI  - Electrodeposition polymers as immobilization matrices in amperometric biosensors:
      improved polymer synthesis and biosensor fabrication.
AB  - Electrodeposition polymers can be precipitated on electrode surfaces upon
      electrochemical-induced modulations of the pH value in the diffusion zone in
      front of the electrode. The formed polymer films can be used as immobilization
      matrices in amperometric biosensors. In order to rationally control the thus
      obtained biosensor properties, it is indispensable to develop strategies for the
      reproducible synthesis of electrodeposition polymers as well as methods for the
      non-manual and reproducible sensor fabrication. Based on instrumental
      developments such as a specifically designed parallel synthesizer with improved
      stirring and temperature control, an automatic pipetting robot for the
      preparation of the monomer mixtures and controlled removal of polymerization
      inhibitors, the reproducible synthesis of libraries of electrodeposition polymers
      was achieved. Moreover, the polymerization process could be monitored using in
      line thermocouples, and it could be shown that the chosen strategies led to
      reproducible polymerization reactions. By adaptation of an electrochemical
      robotic system integrating a Au microtiter plate and automatic electrode cleaning
      by means of a polishing wheel reproducible biosensor fabrication using glucose
      oxidase as a model enzyme could be demonstrated. These results open the route for
      the rational development of biosensors and control of the sensor properties by
      choosing specifically designed electrodeposition polymers.

PMID- 19763553
TI  - Utility of MRI in the follow-up of pyogenic spinal infection in children.
AB  - BACKGROUND: MRI is used at an increasing rate in evaluation of pediatric spinal
      infections both at the time of diagnosis and in follow-up. However, the impact of
      MRI in follow-up has been rarely evaluated to date. OBJECTIVE: To evaluate serial
      follow-up spinal MRI changes compared to clinical outcome and assess their impact
      on clinical management. MATERIALS AND METHODS: All pediatric (<18 years) patients
      with pyogenic spinal infection over a 9-year period with at least one follow-up
      after treatment were included. Atypical infections were excluded. RESULTS: We
      examined 35 whole-spine and 16 localized spinal scans from 17 patients (2 months
      to 16 years, 9F:8 M) who had 51 follow-ups done 2 weeks to 4.75 years after
      baseline. Seven children (41%) younger than 3 years underwent 33 follow-ups
      (65%); most required GA or sedation. Short-term follow-up scans demonstrated
      epidural and/or paraspinal soft-tissue changes correlating with clinical status
      and laboratory findings in all cases. However, MRI showed that bone and/or disc
      abnormalities continued and progressed in some cases despite clinical
      improvement. Long-term follow-up scans showed bone, disc and soft-tissue changes
      1-3 years after baseline, despite children being symptom free. Extension of
      antibiotics occurred in 47% of children partly based on follow-up MRI.
      CONCLUSION: Epidural and paraspinal soft-tissue changes correlated with
      children's clinical symptoms. Progression of bone and disc changes can manifest
      despite adequate clinical response. Long-term or serial routine follow-ups were
      not necessary. Management should be made based on clinical response.

PMID- 19763554
TI  - Ultrasonographic detection of intracranial melanocytosis in an infant.
AB  - An infant who had an extensive cutaneous melanotic nevus with satellite lesions
      had cranial US for an unrelated problem. Small spherical echogenic foci in the
      cerebral and cerebellar parenchyma were identified. Subsequent MRI confirmed
      these as characteristic of melanotic deposits, thereby identifying this infant as
      having neurocutaneous melanosis.

PMID- 19763555
TI  - Brain malformations associated with epignathus: a clue for the correct prenatal
      diagnosis.
AB  - We present a case of epignathus (oral teratoma) with midline intracranial
      associated malformations. This is a rare report of epignathus diagnosed in utero
      with fetal MRI description of these midline brain malformations, including
      duplication of the pituitary gland. This case is an example of how these
      intracranial findings led to the correct diagnosis of a small fetal oral mass.

PMID- 19763556
TI  - Membranous croup (exudative tracheitis or membranous laryngotracheobronchitis).

PMID- 19763557
TI  - Congenital pseudarthrosis of the clavicle.
AB  - BACKGROUND: Congenital pseudarthrosis is an uncommon anomaly poorly referred to
      in the pediatric literature. OBJECTIVE: To describe congenital pseudarthrosis in
      children. We discuss the presentation, clinical symptomatology, and treatment.
      MATERIALS AND METHODS: We reviewed the records of four children with congenital
      pseudarthrosis from 1990 to 2009 at the radiology department of Texas Scottish
      Rite Hospital for Children. RESULTS: Four girls ages 4 through 14 were
      identified. Three children presented with a bulge in the mid-clavicle as a chief
      complaint. The fourth child (14 years old) had bluish discoloration of the right
      upper extremity with venous distention. Three of the four did not have other
      abnormalities, while the 14-year-old had exostosis on the left hand. The mid
      portion of the right clavicle was involved in all four children. Three of the
      four were treated surgically. CONCLUSION: Congenital pseudarthrosis of the
      clavicle is an uncommon anomaly found mostly in girls and in the mid-right
      clavicle.

PMID- 19763558
TI  - Segmental dilatation of the ileum in a healthy adolescent.
AB  - Segmental intestinal dilatation is a rare entity presenting overwhelmingly in
      infants and young children with congenital malformations, anemia, or history of
      gastrointestinal pathology, characterized by a focally distended segment of bowel
      with abrupt transition points without an obstructing barrier. We present a 16
      year-old girl with no significant medical history who presented with bowel
      obstruction clinically. Segmental dilatation of the ileum was evident on a CT
      scan and small bowel series. Following surgical resection, pathologic examination
      of the segment revealed the presence of heterotopic gastric mucosa. The girl's
      symptoms resolved after surgery. Awareness of the imaging presentation of this
      entity can inform the evaluation of older children with nonspecific symptoms
      mimicking bowel obstruction.

PMID- 19763559
TI  - Decreased aortic growth and middle aortic syndrome in patients with neuroblastoma
      after radiation therapy.
AB  - BACKGROUND: Long-term CT follow-up studies are required in pediatric patients who
      have received intraoperative radiation therapy (IORT) and external beam radiation
      therapy (EBRT) to assess vascular toxicities and to determine the exact
      complication rate. OBJECTIVE: To analyze with CT the effects of radiation therapy
      (RT) on the growth of the aorta in neuroblastoma patients. MATERIALS AND METHODS:
      Abdominal CT scans of 31 patients with intraabdominal neuroblastoma (stage II
      IV), treated with RT (20 IORT+/-EBRT, 11 EBRT alone), were analyzed
      retrospectively. The diameter of the abdominal aorta was measured before and
      after RT. These data were compared to normal and predicted normal aortic
      diameters of children, according to the model of Fitzgerald, Donaldson and
      Poznanski (aortic diameter in centimeters = 0.844 + 0.0599 x age in years), and
      to the diameters of a control group of children who had not undergone RT.
      Statistical analyses for the primary aims were performed using the chi-squared
      test, t-test, Mann-Whitney test, nonparametric Wilcoxon matched-pairs test and
      analysis of variance for repeated measures. Clinical files and imaging studies
      were evaluated for signs of late vascular complications of neuroblastoma patients
      who had received RT. RESULTS: The mean diameter before and after RT and the
      growth of the aorta were significantly lower than expected in patients with
      neuroblastoma (P<0.05 for each) and when compared to the growth in a control
      group with normal and nonirradiated aortas. Among the patients who had received
      RT, there was no difference due to the type of RT. Seven patients from the IORT+/
      EBRT group developed vascular complications, which included hypertension (five),
      middle aortic syndrome (two), death due to mesenteric ischemia (one) and critical
      aortic stenosis, which required aortic bypass surgery (two). CONCLUSION: Patients
      with neuroblastoma who had received RT showed impaired growth of the abdominal
      aorta. Significant long-term vascular complications occurred in seven patients
      who received IORT+/-EBRT. Thus, CT evaluation of patients with neuroblastoma who
      receive RT should include not only reports of changes in tumor extension, but
      also documentation of perfusion, and the size and growth of the aorta and its
      branches over time.

PMID- 19763560
TI  - Tumefactive intracranial presentation of precursor B-cell acute lymphoblastic
      leukemia.
AB  - In children, leukemia is the most common malignancy, and approximately 75% of
      leukemias are acute lymphoblastic leukemia (ALL). Central nervous system leukemia
      is found at diagnosis in fewer than 5% of children with ALL. Leukemic
      intracranial masses have been described with acute myeloid leukemia, but ALL
      presenting as a mass lesion is rare. We describe a unique case of an intracranial
      confirmed precursor B cell (pre-B) ALL mass in a 13-year-old girl that was
      diagnosed by brain CT, MRI and cerebral angiography, and confirmed by biopsy.
      This report details pertinent history and distinguishing imaging features of an
      intracranial ALL tumefaction.

PMID- 19763561
TI  - Minimal models of electric potential oscillations in non-excitable membranes.
AB  - Sustained oscillations in the membrane potential have been observed in a variety
      of cellular and subcellular systems, including several types of non-excitable
      cells and mitochondria. For the plasma membrane, these electrical oscillations
      have frequently been related to oscillations in intracellular calcium. For the
      inner mitochondrial membrane, in several cases the electrical oscillations have
      been attributed to modifications in calcium dynamics. As an alternative, some
      authors have suggested that the sustained oscillations in the mitochondrial
      membrane potential induced by some metabolic intermediates depends on the direct
      effect of internal protons on proton conductance. Most theoretical models
      developed to interpret oscillations in the membrane potential integrate several
      transport and biochemical processes. Here we evaluate whether three simple
      dynamic models may constitute plausible representations of electric oscillations
      in non-excitable membranes. The basic mechanism considered in the derivation of
      the models is based upon evidence obtained by Hattori et al. for mitochondria and
      assumes that an ionic species (i.e., the proton) is transported via passive and
      active transport systems between an external and an internal compartment and that
      the ion affects the kinetic properties of transport by feedback regulation. The
      membrane potential is incorporated via its effects on kinetic properties. The
      dynamic properties of two of the models enable us to conclude that they may
      represent alternatives enabling description of the generation of electrical
      oscillations in membranes that depend on the transport of a single ionic species.

PMID- 19763562
TI  - From spin-labeled proteins to in vivo EPR applications.
AB  - This is a historical overview of the advent of applications of spin labeling to
      biological systems and the subsequent developments from the perspective of a
      scientist who was working as a Ph.D. student when the technique was conceived and
      was fortunate enough to participate in its development. In addition, the
      historical development of in vivo applications of EPR on animals and other living
      systems is described from a personal perspective.

PMID- 19763563
TI  - Intercrossing of phage genomes in a phage cocktail and stable coexistence with
      Escherichia coli O157:H7 in anaerobic continuous culture.
AB  - The emergence of phage-resistant cells is the most serious problem for realizing
      phage therapy and is observed frequently if only one phage strain is used against
      a particular bacterium. By contrast, using multiple phages (phage cocktail) can
      delay or control the appearance of phage-resistant cells. Anaerobic continuous
      culturing of Escherichia coli O157:H7 and a cocktail of EP16, PP17, and SP22
      phages were conducted. Comparison of the restriction fragment length polymorphism
      (RFLP) pattern of each phage genome showed a pattern different from wild type.
      Furthermore, the RFLP pattern of mutant phages consisted of fragments of PP17 and
      SP22 genome, suggesting both phages had infected the same host simultaneously
      (superinfection) and exchanged genomic DNA. Through observation of the binding of
      SYBR Gold-stained mutant phage to individual phage-resistant cells (RC), we found
      that clonal RC cultures were heterogeneous in their ability to bind mutant phage.
      The ratio of susceptibility was a few percent, which suggested that a minority of
      the RC population was susceptible to phage, and this heterogeneity contributes to
      the stable coexistence of RC and chimeric phages. The ratio of susceptible cells
      did not change appreciably from bacterial generation to generation.

PMID- 19763564
TI  - Engineering of cyclodextrin glucanotransferases and the impact for
      biotechnological applications.
AB  - Cyclodextrin glucanotransferases (CGTases) are industrially important enzymes
      that produce cyclic alpha-(1,4)-linked oligosaccharides (cyclodextrins) from
      starch. Cyclodextrin glucanotransferases are also applied as catalysts in the
      synthesis of glycosylated molecules and can act as antistaling agents in the
      baking industry. To improve the performance of CGTases in these various
      applications, protein engineers are screening for CGTase variants with higher
      product yields, improved CD size specificity, etc. In this review, we focus on
      the strategies employed in obtaining CGTases with new or enhanced enzymatic
      capabilities by searching for new enzymes and improving existing enzymatic
      activities via protein engineering.

PMID- 19763565
TI  - Potential impact of (68)Ga-DOTATOC PET/CT on stereotactic radiotherapy planning
      of meningiomas.
AB  - PURPOSE: Since meningiomas show a high expression of somatostatin receptor
      subtype 2, PET with (68)Ga-DOTATOC was proposed as an additional imaging modality
      beside CT and MRI for planning radiotherapy. We investigated the input of (68)Ga
      DOTATOC-PET/CT on the definition of the "gross tumour volume" (GTV) in
      meningiomas, in order to assess the potential value of this method. METHODS:
      Prior to radiotherapy, 42 patients with meningiomas (26 f, 16 m, mean age 55)
      underwent MRI and (68)Ga-DOTATOC-PET/CT examinations. HISTORY: operated n = 24,
      radiotherapy n = 1, operation and radiotherapy n = 8, no treatment n = 9. PET/CT
      and MRI data were co-registered using a BrainLAB workstation. For comparison, the
      GTV was defined first under consideration of CT and MRI data, then using PET
      data. RESULTS: 3/42 patients were excluded from the analysis (two with negative
      PET results, one with an extensive tumour, not precisely delineable by MRI or
      PET/CT). The average GTV(CT/MRI) was 22(+/-19)cm(3); GTV(PET) was 23(+/-20)cm(3).
      Additional GTV, obtained as a result of PET was 9(+/-10)cm(3) and was observed in
      patients with osseous infiltration. In some pre-treated patients there were
      intratumoural areas (as identified in CT/MRI) without SR-expression (7(+/
      11)cm(3)). Common GTV as obtained by both CT/MRI and PET was 15(+/-14)cm(3). The
      mean bi-directional difference between the GTV(CT/MRI) and GTV(PET) accounted to
      16(+/-15)cm(3) (93%, p < 0.001). In a subgroup of seven patients with multiple
      meningiomas, PET showed a total of 19 lesions; nine of them were not recognizable
      by CT or MRI. CONCLUSION: (68)Ga-DOTATOC-PET enables delineation of SR-positive
      meningiomas and delivers additional information to both CT and MRI regarding the
      planning of stereotactic radiotherapy. The acquisition on a PET/CT scanner helps
      to estimate the relation of PET findings to anatomical structures and is
      especially useful for detection of osseous infiltration. (68)Ga-DOTATOC-PET also
      allows detection of additional lesions in patients with multiple meningiomas.

PMID- 19763566
TI  - p-Isothiocyanatobenzyl-desferrioxamine: a new bifunctional chelate for facile
      radiolabeling of monoclonal antibodies with zirconium-89 for immuno-PET imaging.
AB  - PURPOSE: Immuno-PET is an emerging imaging tool for the selection of high
      potential antibodies (mAbs) for imaging and therapy. The positron emitter
      zirconium-89 ((89)Zr) has attractive characteristics for immuno-PET with intact
      mAbs. Previously, we have described a multi-step procedure for stable coupling of
      (89)Zr to mAbs via the bifunctional chelate (BFC) tetrafluorophenol-N
      succinyldesferal (TFP-N-sucDf). To enable widespread use of (89)Zr-immuno-PET, we
      now introduce the novel BFC p-isothiocyanatobenzyl-desferrioxamine B (Df-Bz-NCS)
      and compare its performance in (89)Zr-immuno-PET with the reference BFC TFP-N
      sucDf. METHODS: Three mAbs were premodified with Df-Bz-NCS and labeled with
      (89)Zr at different pHs to assess the reaction kinetics and robustness of the
      radiolabeling. Stability of both (89)Zr-Df-Bz-NCS- and (89)Zr-N-sucDf-conjugates
      was evaluated in different buffers and human serum. Comparative biodistribution
      and PET studies in tumor-bearing mice were undertaken. RESULTS: The selected
      conjugation conditions resulted in a chelate:mAb substitution ratio of about
      1.5:1. Under optimal radiolabeling conditions (pH between 6.8-7.2), the
      radiochemical yield was >85% after 60 min incubation at room temperature,
      resulting in radioimmunoconjugates with preserved integrity and immunoreactivity.
      The new radioimmunoconjugate was very stable in serum for up to 7 days at 37
      degrees C, with <5% (89)Zr release, and was equally stable compared to the
      reference conjugate when stored in the appropriate buffer at 4 degrees C. In
      biodistribution and imaging experiments, the novel and the reference
      radioimmunoconjugates showed high and similar accumulation in tumors in nude
      mice. CONCLUSIONS: The novel Df-Bz-NCS BFC allows efficient and easy preparation
      of optimally performing (89)Zr-labeled mAbs, facilitating further exploration of
      (89)Zr-immuno-PET as an imaging tool.

PMID- 19763567
TI  - Technique and short-term results of ankle arthrodesis using anterior plating.
AB  - Clinical and biomechanical trials have shown that rigid internal fixation during
      ankle arthrodesis leads to increased rates of union and is associated with a
      reduced infection rate, union time, discomfort and earlier mobilisation compared
      with other methods. We describe our technique of ankle arthrodesis using anterior
      plating with a narrow dynamic compression plate (DCP). Between 2004 and 2007, 29
      patients with a mean age of 24.4 years (range 18-42) had ankle arthrodesis using
      an anteriorly placed narrow DCP. Twenty-two patients were post-traumatic and
      seven were paralytic (five after spine fracture and two after common peroneal
      nerve injury). Follow-up was between 12 and 18 months (average 14 months). A rate
      of fusion of 100% was achieved at an average of 12.2 weeks. According to the
      Mazur ankle score, 65.5% had excellent, 20.7% good and 13.8% fair results. Ankle
      arthrodesis using an anteriorly placed narrow DCP is a good method to achieve
      ankle fusion in many types of ankle arthropathies.

PMID- 19763568
TI  - Objective assessments of medial osteoarthritic knee severity by MRI: new computer
      software to evaluate femoral condyle contours.
AB  - An irregular contour of the medial femoral condyle (MFC) on magnetic resonance
      imaging (MRI) appears to indicate the severity of medial-type knee osteoarthritis
      (OA). The purpose of this study was to establish a system to enable objective
      assessments of OA knee severity using newly developed software that semi
      automatically measures irregularity of the MFC. (1) We evaluated 48 patients aged
      50-83 years with 55 knees of medial-type OA. The following scores were recorded:
      Lysholm score, visual analogue scale (VAS) and the Japanese Knee Osteoarthritis
      Measure (JKOM). MFC irregularity was automatically calculated by newly programmed
      computer software. Four parameters for condyle irregularity were calculated: (a)
      the average thickness of the contour (ATC), (b) the ratio of the upper surface
      length to the lower surface length of the contour (RUL), (c) average squared
      thickness of the contour (ASTC) and (d) standard deviation of the contour
      thickness (SDC). (2) Nine knees that underwent total knee arthroplasty were
      further analysed histopathologically and compared with irregularity score.
      Statistically, the RUL and SDC were significantly correlated with the Lysholm
      score, VAS and JKOM, with good reliability. Histological examinations showed that
      an irregular contour reflected the density of cystic lesions formed in
      subchondral bone. An irregularity of MFC on MRI is correlated with OA disease
      severity clinically and histopathologically. The new computer software is useful
      to objectively assess OA disease severity.

PMID- 19763569
TI  - To what extent does leg length discrepancy impair motor activity in patients
      after total hip arthroplasty?
AB  - The aim of this study was to evaluate the effects of limb lengthening up to 20 mm
      after THA on symmetry of hip kinematics and kinetics during common activities of
      daily living. Twenty patients (age range 49-80 years) operated on with Link
      Lubinus II THA, with lateral access and a mean follow-up of 16 months, were
      assessed by gait analysis during level walking, stair ascending and descending.
      The time-distance, hip kinetics and kinematics values were statistically compared
      between the operated side and the non-operated side in order to assess symmetry.
      The 12-item Questionnaire was used to assess satisfaction and personal perception
      of limb lengthening. Mean value of limb lengthening after THA was 11 mm (SD 6).
      Minor abnormalities were found in the kinematics and kinetics of the operated and
      non-operated hips during level walking and stair climbing. The score of the
      questionnaire corresponded to a high level of satisfaction after THA and only two
      patients complained of limping independent from the amount of discrepancy. From
      this study we can conclude that a leg length inequality in the range of 1-20 mm
      does not impair the symmetry of time-distance parameters and of hip kinematics
      and kinetics during gait and stairs walking. Although objective, gait analysis
      data did not correspond to patient's perception of discrepancy, which is
      subjective and irrespective of the amount of lengthening. There is biomechanical
      evidence that a limb lengthening of up to two centimetres after THA in general
      does not need to be corrected by means of a contralateral shoe lift. Individual
      decisions to the contrary need to be justified.

PMID- 19763570
TI  - Role of radiography, MRI and FDG-PET/CT in diagnosing, staging and therapeutical
      evaluation of patients with multiple myeloma.
AB  - Multiple myeloma is a malignant B-cell neoplasm that involves the skeleton in
      approximately 80% of the patients. With an average age of 60 years and a 5-years
      survival of nearly 45% Brenner et al. (Blood 111:2516-2520,35) the onset is to be
      classified as occurring still early in life while the disease can be very
      aggressive and debilitating. In the last decades, several new imaging techniques
      were introduced.The aim of this review is to compare the different techniques
      such as radiographic survey, multidetector computed tomography (MDCT), whole-body
      magnetic resonance imaging (WB-MRI), fluorodeoxyglucose positron emission
      tomography-(FDG-PET) with or without computed tomography(CT), and 99mTc
      methoxyisobutylisonitrile (99mTc-MIBI) scintigraphy. We conclude that both FDG
      PET in combination with low-dose CT and whole-body MRI are more sensitive than
      skeleton X-ray in screening and diagnosing multiple myeloma. WB-MRI allows
      assessment of bone marrow involvement but cannot detect bone destruction, which
      might result in overstaging. Moreover,WB-MRI is less suitable in assessing
      response to the rapythan FDG-PET. The combination of PET with low-dose CT can
      replace the golden standard, conventional skeletal survey. In the clinical
      practise, this will result in upstaging,due to the higher sensitivity.

PMID- 19763571
TI  - A multi-center phase II study of docetaxel plus cisplatin as first-line therapy
      in patients with metastatic squamous cell esophageal cancer.
AB  - OBJECTIVE: The objective of this study was to evaluate the efficacy and toxicity
      of docetaxel and cisplatin combination chemotherapy in patients with metastatic
      esophageal cancer. METHODS: Patients with untreated metastatic squamous cell
      esophageal cancer, which was histologically proven with at least one measurable
      lesion, were eligible for the study. Docetaxel 70 mg/m(2) and cisplatin 70
      mg/m(2) were intravenously given on day 1 of 21 days schedule. RESULTS: From
      December 2004 to December 2007, total of 39 patients (M/F = 39/0) were enrolled.
      The median age was 65 years. Thirty-four patients were evaluable for response.
      There were 3 (7.7%) complete remission, 10 (25.6%) partial remission, 11 (28.2%)
      stable disease, and 10 (25.6%) progression disease. The objective tumor response
      rate was 33.3% in intention-to-treat (ITT). Median PFS was 5.0 months and median
      survival was 8.3 months. Median number of cycles administered was 3. The relative
      dose intensity of docetaxel and cisplatin was 92 and 91%, respectively. This
      treatment was comparatively tolerated with grade 3/4 neutropenia in 20.5%/10.3%,
      grade 3 infection in 2.6% of patients. CONCLUSION: Docetaxel plus cisplatin
      combination chemotherapy showed promising antitumor activity with manageable
      toxicities in patients with metastatic squamous esophageal cancer.

PMID- 19763572
TI  - A randomized comparative study of high-dose and low-dose hepatic arterial
      infusion chemotherapy for intractable, advanced hepatocellular carcinoma.
AB  - PURPOSE: Hepatic arterial infusion chemotherapy (HAIC) has been reported to be
      effective in patients with advanced hepatocellular carcinoma (HCC). METHODS: In
      this multicenter, prospective, open-labeled, clinical trial, we randomly assigned
      68 patients with advanced HCC to receive either low-dose [n = 32, 5-fluorouracil
      (FU), 170 mg/m(2) and cisplatin, 7 mg/m(2) on days 1-5] or high-dose HAIC (n =
      36, 5-FU, 500 mg/m(2) on days 1-3 and cisplatin, 60 mg/m(2) on day 2) every 4
      weeks via an implantable port system. RESULTS: A total of 207 cycles of HAIC was
      given to the 68 patients. Overall, 6 patients (8.8%) achieved a partial response
      and 21 patients (30.9%) had stable disease. The objective response rate (CR + PR)
      was significantly improved in the high-dose group compared to the low-dose group
      (16.7% vs. 0%, P = 0.024). The median time to disease progression and overall
      survival were slightly prolonged in the high-dose group compared to the low-dose
      group (median survival, 193 vs. 153 days; P = 0.108; median time to disease
      progression, 145 vs. 90 days; P = 0.095). Multivariate analysis showed that tumor
      response to treatment [P = 0.007, RR 2.27 (95% CI, 1.248-4.132)] was the only
      factor associated with overall survival. All adverse events were tolerable and
      successfully managed in both treatment groups. CONCLUSIONS: Both HAIC regimens
      are safe and effective in patients with advanced HCC. High-dose HAIC achieves a
      better tumor response compared to low-dose HAIC.

PMID- 19763573
TI  - PSC833, cyclosporine analogue, downregulates MDR1 expression by activating JNK/c
      Jun/AP-1 and suppressing NF-kappaB.
AB  - PURPOSE: Multidrug resistance (MDR) is one of the major causes of clinical cancer
      chemotherapy failure. PSC833 is well known as a non-immunosuppressant
      cyclosporine analogue that functionally inhibits P-glycoprotein (Pgp), a product
      of the MDR1 gene. We investigated whether PSC833 could also alter MDR1 expression
      and, if so, which mitogen-activated protein kinases (MAPKs) and nuclear factor
      kappaB (NF-kappaB) pathways were involved in this event. METHODS: MTT assay and
      flow cytometry were used for the analysis of cytotoxicity and intracellular drug
      accumulation, respectively. RT-PCR and Western blot assays for analysis of gene
      expression and electrophoretic mobility shift assays for determination of DNA
      binding activity of transcription factors were used. RESULTS: The doxorubicin
      resistant lung cancer cell subline (SK-MES-1/DX1000), selected from SK-MES-1/WT
      cells, upregulated MDR1 expression, thereby showing MDR phenotypes. PSC833
      sensitized SK-MES-1/DX1000 cells to doxorubicin. PSC833 (5 microM) also decreased
      the intracellular accumulation of fluorescent Pgp substrates such as rhodamine
      123 and daunorubicin in SK-MES-1/DX1000 cells. PSC833 downregulated MDR1 mRNA and
      Pgp expression in a time- and concentration-dependent manner. PSC833 activated c
      Jun NH2-terminal kinase (JNK)/c-Jun and enhanced AP-1 DNA-binding activity, but
      suppressed nuclear translocation of NF-kappaB, all of which were prevented by
      pretreatment with a JNK inhibitor SP600125. CONCLUSIONS: These results indicate
      that PSC833 not only sensitizes SK-MES-1/DX1000 cells to doxorubicin by enhancing
      drug accumulation, but also downregulates MDR1 expression by activating JNK/c
      Jun/AP-1 and suppressing NF-kappaB.

PMID- 19763574
TI  - Role of microglia in neuronal degeneration and regeneration.
AB  - Microglial cells, the resident macrophage population of the central nervous
      system (CNS), actively scan tissue under both normal and pathologic contexts.
      Their resulting engagement can become either neuroprotective or neurotoxic,
      leading to amelioration or aggravation of disease progression. In this review, we
      focus on the molecular signaling molecules involved in microglial responses and
      discuss observations demonstrating the diverse effects of microglia in animal
      models of CNS diseases.

PMID- 19763575
TI  - Novel approaches for identifying target antigens of autoreactive human B and T
      cells.
AB  - Antigen-specific immune responses in multiple sclerosis have been studied for
      decades, but the target antigens of the putatively autoaggressive B and T cells
      still remain elusive. Here, we summarize recent strategies which are based on the
      direct analysis of biopsy or autopsy specimens from patients. Since this material
      is extremely scarce, the experimental methods need to be exceptionally sensitive.
      We describe technologies to distinguish (auto) aggressive T cells from irrelevant
      bystander lymphocytes by analyzing clonal expansions in relation to the
      morphological location of the cells in the tissue lesions. We then discuss
      approaches to clone matching alpha- and beta-chains of the antigen-specific T
      cell receptor (TCR) molecules from single T cells. This is necessary because
      usually, several clones are expanded and are diluted by many irrelevant cells.
      The matching TCR chains from individual T cells can be resurrected in hybridoma
      cells which may then be used for antigen searches. We discuss strategies to
      identify antigens of gammadelta- and alphabeta-TCR molecules, such as biochemical
      methods, candidate antigens, human leukocyte antigen requirements, synthetic
      peptide, and cDNA libraries. These strategies are tailored to characterize the
      antigens of the membrane-anchored, low-affinity TCR molecules. The strategies to
      identify (auto) reactive B cells or immunoglobulin (Ig) molecules are
      fundamentally different, because Ig molecules are water-soluble and have high
      affinities. We further discuss proteome-based approaches, techniques that analyze
      Ig-chains from single B cells, and a repertoire-based method that compares Ig
      proteomes and Ig-transcriptomes. The first method detects Ig antigens directly,
      whereas the latter two methods allow reconstruction of Ig molecules, which can be
      used for antigen searches.

PMID- 19763576
TI  - Encephalitis and epilepsy.
AB  - Epileptic seizures can be induced by a variety of underlying diseases. One of the
      causes is brain inflammation or encephalitis. In this review, we focus on three
      different kinds of encephalitis known to occur with seizures: Rasmussen
      encephalitis, paraneoplastic encephalitis, and nonparaneoplastic encephalitis. We
      describe pathogenic similarities and differences in the immunological response
      and cell death in the central nervous system of these three types of encephalitis
      and discuss the present ideas regarding the underlying etiology of these
      diseases.

PMID- 19763577
TI  - LEAFY COTYLEDON2 gene expression and auxin treatment in relation to embryogenic
      capacity of Arabidopsis somatic cells.
AB  - The expression pattern of the LEC2 gene during somatic embryogenesis (SE) in
      Arabidopsis explants (immature zygotic embryos) induced in vitro was followed,
      using real-time quantitative PCR (qRT-PCR). The analysis revealed differential
      expression of LEC2 transcripts within a 30 days time course of somatic embryo
      development. A significant auxin-dependent upregulation of the LEC2 gene was
      found to be associated with the induction phase of SE. In contrast to embryogenic
      culture the level of LEC2 expression was noticeably lower in non-embryogenic
      callus of Col-0 and hormonal mutants (cbp20 and axr4-1) with low SE-efficiency.
      The study with 35S::LEC2-GR transgenic plants showed that overexpression of LEC2
      can compensate for the auxin requirement, and that transgenic explants formed
      somatic embryos when cultured in vitro under auxin-free conditions. However,
      unlike in auxin-induced SE, intense callus formation preceded the embryogenic
      response triggered via LEC2 overexpression, suggesting an indirect pathway of
      morphogenesis. Moreover, a negative interaction between auxin treatment and LEC2
      overexpression in terms of SE efficiency was observed, as transgenic explants
      cultured on auxin medium displayed a significantly reduced level of embryogenic
      potential. The study provides further experimental evidence that in the
      determination of the embryogenic response in Arabidopsis somatic cells, a close
      link exists between auxin and the LEC2 activity.

PMID- 19763578
TI  - Comparison of STIR turbo SE imaging and diffusion-weighted imaging of the lung:
      capability for detection and subtype classification of pulmonary adenocarcinomas.
AB  - OBJECTIVE: The aim of the study was to evaluate the diagnostic performance of
      diffusion-weighted imaging (DWI) for detection and subtype classification in
      pulmonary adenocarcinomas through comparison with short TI inversion recovery
      turbo spin-echo imaging sequence (STIR). METHODS: Thirty-two patients (mean age,
      65.2 years) with 33 adenocarcinomas (mean diameter, 27.6 mm) were enrolled in
      this study. The detection rates of both sequences were compared. The ADC values
      on DWI and the contrast ratio (CR) between cancer and muscle on STIR were
      measured and those were compared across subtype classifications. Finally, ROC
      based positive tests were performed to differentiate subtype classifications, and
      differentiation capabilities were compared. RESULTS: The DWI detection rate [85%
      (28/33)] was significantly lower than that of STIR [100% (33/33), P < 0.05]. The
      ADC values showed no significant difference regarding subtype classification;
      however, the CRs of bronchio-alveolar carcinomas (BACs) were significantly lower
      than those of other types (P < 0.05). When threshold values for differentiating
      BACs from others were adapted, the sensitivity and accuracy of DWI were
      significantly lower than those of STIR (P < 0.05). For differentiating
      adenocarcinomas with mixed subtypes from those with no BA component, there were
      no significant differences between the two sequences. CONCLUSION: STIR is more
      sensitive for detection and subtype classification than DWI.

PMID- 19763579
TI  - Angiographic and artefact-free computed tomography imaging of experimental
      aneurysms embolised with hydrogel filaments.
AB  - OBJECTIVES: We compared experimental rabbit carotid bifurcation aneurysms
      embolised with platinum coils or hydrogel filaments by using digital subtraction
      angiography (DSA) and computed tomography angiography (CTA). METHODS:
      Embolisation was performed using platinum coils (n = 2), hydrogel filaments
      loaded with iodine (n = 3) and hydrogel filaments loaded with barium sulphate (n
      = 3). In one case, a stent was deployed in the parent vessel to determine the
      effect of hydrogel filaments on stent visualisation. DSA evaluations occurred
      immediately post-treatment. CTA evaluations occurred at 0-13 weeks post
      treatment. The DSA and CTA images were evaluated for the lack of artefacts and
      the visibilities of the embolic mass, individual coils and residual flow in the
      aneurysm sac and neck. RESULTS: The DSA results were largely concordant among the
      three groups. The embolic masses were readily evident with some individual coils
      being distinguished. In the aneurysms embolised with hydrogel filaments,
      visualisation of the individual coils, residual flow and stent with minor or no
      artefacts was possible using CTA. On the other hand, the beam hardening artefacts
      precluded analysis of aneurysms embolised with platinum coils. CONCLUSION: CTA
      compatible embolic devices could have wide applications in diverse locations
      throughout the vasculature, particularly in combination with stents or stent
      grafts.

PMID- 19763580
TI  - Carcinoma of the breast wire localisation post nuclear medicine sentinel lymph
      node imaging. Are radiologists receiving a significant dose?
AB  - OBJECTIVE: To assess the radiation dose received by the radiologist when
      performing wire localisation for axillary radio-isotope sentinel node imaging
      guided biopsy in patients with impalpable breast cancers treated with breast
      preserving excision. When wire placement follows radio-isotope sentinel node
      imaging (RSNI) the radiologist is exposed to a radiation risk that has never been
      previously assessed. METHODS: Radiation doses to radiologists performing
      ultrasound-guided localisation following nuclear medicine sentinel node imaging
      were measured for procedures on the day of surgery (20 MBq) and also on the day
      before surgery (40 MBq). These measurements were compared with theoretically
      calculated doses. RESULTS: Twelve patients showed comparable results between
      measurements and estimated doses. The mean measured dose was 1.8 muSv (estimated
      1.8 muSv) for same-day and 4.8 muSv (estimated 3.4 muSv) for next-day surgery
      cases. At worst, radiologists who perform 36 wire localisations per year
      immediately following RSNI receive a radiation dose of 0.17 mSv. CONCLUSIONS:
      This study highlights the need to inform radiologists of the relative risk when
      performing pre-surgical localisation after RSNI. This risk should be justified
      locally in accordance with the total dose received by the localising radiologist.
      Particular consideration should be given to pregnant staff and the possibility of
      performing wire localisations before radio-isotope injection.

PMID- 19763581
TI  - Imaging of adult astrocytic brain tumours with 7 T MRI: preliminary results.
AB  - PURPOSE: In this study tumour vascularity and necrosis of intracranial
      astrocytomas were compared using 7 T and 1.5 T magnetic resonance imaging (MRI).
      METHODS: Fifteen patients with histologically proven astrocytomas (WHO grades II
      IV) were prospectively examined at 1.5 T (Magnetom Espree or Sonata) and 7 T
      (Magnetom 7 T, Siemens, Erlangen, Germany) with T2*-w (weighted), T1-w with (only
      a subset of five patients at 7 T) and without contrast medium, T2-w and proton
      density (PD)-w MRI. Clinically used 1.5 T sequences were adapted to 7 T.
      Histological findings and T2*-w MR images at both field strengths were compared
      for the presence of assumed tumour microvascularity and necrosis. Two diffusely
      infiltrating astrocytomas, four anaplastic astrocytomas and nine glioblastomas
      were included. RESULTS: T2*-w images depicted susceptibility patterns
      representing presumed tumour microvascularity in 8 out of 15 (53%) gliomas at 7 T
      compared with 5 out of 15 (33%) gliomas at 1.5 T. Compared with 1.5 T MRI three
      additional necrotic tumour areas were depicted only on 7 T T2- and T2*-w images
      of one glioblastoma. On T1-w MR images, contrast enhancement of five out of five
      glioblastomas was similar at both field strengths. CONCLUSION: 7 T gradient-echo
      sequences provide excellent image contrast of presumed microvasculature and
      necrosis in astrocytomas.

PMID- 19763582
TI  - Bias, underestimation of risk, and loss of statistical power in patient-level
      analyses of lesion detection.
AB  - PURPOSE: Sensitivity and the false positive rate are usually defined with the
      patient as the unit of observation, i.e., the diagnostic test detects or does not
      detect disease in a patient. For tests designed to find and diagnose lesions,
      e.g., lung nodules, the usual definitions of sensitivity and specificity may be
      misleading. In this paper we describe and compare five measures of accuracy of
      lesion detection. METHODS: The five levels of evaluation considered were patient
      level without localization, patient level with localization, region of interest
      (ROI) level without localization, ROI level with localization, and lesion level.
      RESULTS: We found that estimators of sensitivity that do not require the reader
      to correctly locate the lesion overstate sensitivity. Patient-level estimators of
      sensitivity can be misleading when there is more than one lesion per patient and
      they reduce study power. Patient-level estimators of the false positive rate can
      conceal important differences between techniques. Referring clinicians rely on a
      test's reported accuracy to both choose the appropriate test and plan management
      for their patients. If reported sensitivity is overstated, the clinician could
      choose the test for disease screening, and have false confidence that a negative
      test represents the true absence of lesions. Similarly, the lower false positive
      rate associated with patient-level estimators can mislead clinicians about the
      diagnostic value of the test and consequently that a positive finding is real.
      CONCLUSION: We present clear recommendations for studies assessing and comparing
      the accuracy of tests tasked with the detection and interpretation of lesions...

PMID- 19763583
TI  - Workplace experience of radiographers: impact of structural and interpersonal
      interventions.
AB  - PURPOSE: Within the framework of organisational development, an assessment of the
      workplace experience of radiographers (RGs) was conducted. The aims of this study
      were to develop structural and interpersonal interventions and to prove their
      effectiveness and feasibility. METHODS: A questionnaire consisting of work
      related factors, e.g. time management and communication, and two validated
      instruments (Workplace Analysis Questionnaire, Effort-Reward Imbalance Scale) was
      distributed to all RGs (n = 33) at baseline (T1). Interventions were implemented
      and a follow-up survey (T2) was performed 18 months after the initial assessment.
      RESULTS: At T1, areas with highest dissatisfaction were communication and time
      management for ambulant patients (bad/very bad, 57% each). The interventions
      addressed adaptation of work plans, coaching in developing interpersonal and team
      leadership skills, and regular team meetings. The follow-up survey (T2) showed
      significantly improved communication and cooperation within the team and improved
      qualification opportunities, whereas no significant changes could be identified
      in time management and in the workplace-related scales 'effort' expended at work
      and 'reward' received in return for the effort. CONCLUSION: Motivating workplace
      experience is important for high-level service quality and for attracting well
      qualified radiographers to work at a place and to stay in the team for a longer
      period.

PMID- 19763584
TI  - New therapies for non-muscle-invasive bladder cancer.
AB  - The treatment of non-muscle-invasive bladder cancer (NMIBC) remains a challenge
      owing to its increased tendency to recur and the possibility of progression to
      potentially dangerous muscle-invasive disease. Treatment outcomes by current
      therapeutic modalities are still not optimal. In recent years, there have been a
      number of substantive advances in the therapeutic options for the management of
      NMIBC. New chemotherapeutic drugs have been introduced, along with efforts made
      to improve the efficacy of existing agents and enhance delivery of agents to the
      bladder. There is also a growing trend toward combination of agents and
      multimodal therapy. Also of considerable interest are the investigation of newer
      approaches such as gene therapy, chemoenhancement and newer forms of
      immunotherapy. Here, we review the recent pre-clinical and clinical developments
      in the treatment of NMIBC, described in the broad categories of immunotherapy,
      chemotherapeutic agents, improved or device-assisted agent delivery and gene
      therapy.

PMID- 19763585
TI  - Wilhelm His (1831-1904) and his contributions   to neuroanatomy.
AB  - INTRODUCTION: The contributions to neuroanatomy by the Swiss scientist Wilhelm
      His, Sr. (1831-1904) are underrepresented in the literature. DISCUSSION: The
      present paper will discuss the life and writings of this pioneer of the
      neurosciences who expanded our knowledge of neurohistology and neuroembryology.

PMID- 19763586
TI  - Suprasellar ganglioglioma presenting with diabetes insipidus in a young boy: a
      rare clinical presentation.
AB  - OBJECTIVE: Gangliogliomas are rare tumors composed of an admixture of glial and
      neuronal components. These usually occur in young patients, who present with
      therapy-resistant seizures. Clinical presentation of ganglioglioma with diabetes
      insipidus is extremely rare with only one case reported earlier in the available
      literature. Due to this rarity, ganglioglioma is not considered in the
      differential diagnosis in a patient with diabetes insipidus. CASE: A 7-year boy
      presented with polyuria, polydipsia, and progressive visual loss for 18 months.
      Investigations revealed diabetes insipidus. Radiographic studies of the brain
      showed a solid and cystic mass in the suprasellar region effacing the third
      ventricle. Intraoperatively, diffuse thickening of bilateral optic nerves and
      optic chiasma was noted and a diagnosis of optic glioma was considered. A biopsy
      of the mass was taken, which on histopathological examination showed features of
      ganglioglioma. The patient was referred for further radiotherapy but was lost to
      follow-up. CONCLUSION: Diabetes insipidus as a presenting symptom of
      ganglioglioma is extremely rare. This benign tumor should be kept in mind in
      patients with central diabetes insipidus and a suprasellar mass lesion. This
      report describes the second such case in the literature.

PMID- 19763587
TI  - Long-term significance of injury to the supraorbital  or supratrochlear nerves
      during frontoorbital advancement  in infancy.
AB  - INTRODUCTION: In a series of 26 infants undergoing frontoorbital advancement in
      their first year of life, the supraorbital and supratrochlear nerves were not
      preserved during surgery in nearly all cases. Of these 26 patients, 25 could be
      followed up postoperatively. RESULTS: None of the children spontaneously
      complained of any sensory disturbances thereafter. In neurologic follow-up
      examinations or telephone interviews 11-81 (median, 39) months after surgery, the
      patients, respectively their parents were explicitly asked for sensory deficits.
      The majority of patients had no sensory disturbances at all; two patients
      reported on dysesthesias when touching the forehead, not affecting them in their
      daily life. CONCLUSIONS: It is concluded that (1) anatomical transsection of the
      supraorbital or supratrochlear nerve in very young patients may be functionally
      fully compensated over time, (2) the preservation of the supraorbital or
      supratrochlear nerve in frontoorbital advancement in patients less than 1 year of
      age is of no major significance in the long term and (3) partial anatomical
      preservation with functional impairment of the nerves may result in dysesthesias
      in the forehead. Therefore, from a practical surgical standpoint, deliberate
      anatomical transsection in this age group may be superior to partial
      morphological preservation of the nerves with subsequent functional impairment.

PMID- 19763588
TI  - Osteosarcoma presenting as hemorrhagic cerebellar metastasis.
AB  - PURPOSE: Osteosarcoma is the most common malignant bone tumor in children and
      adolescents. Brain metastasis from osteosarcoma was once uncommon; however, with
      the advent of chemotherapeutic agents and improved imaging modalities, it has
      become a more common and recognized finding. Brain metastases are, rarely, the
      initial presenting symptom, but instead are a late and preterminal event in the
      disease process. When osteosarcomas manifest in the central nervous system, they
      tend to occur in the gray-white junction in the anterior circulation akin to
      other metastatic lesions in the brain. CASE REPORT: The authors report a case of
      a 16-year-old boy who presented with acute neurological deterioration due to a
      posterior fossa hemorrhage and was subsequently found to have a primary site
      localizing to the metaphysis of the right femur with florid metastatic disease.
      CONCLUSIONS: This is the first case reported in the literature in which an
      osteosarcoma initially presented as cerebral metastasis in the form of a
      posterior fossa hemorrhage with a rapidly deteriorating course.

PMID- 19763589
TI  - Multiple saccular aneurysms of the extracranial and intracranial internal carotid
      artery associated with convexobasia and arachnoid cyst in a 6-year-old boy: a
      case report.
AB  - INTRODUCTION: We report an extremely rare case of multiple saccular aneurysms of
      the extracranial and intracranial internal carotid artery associated with
      convexobasia of the left temporal region and arachnoid cyst in a 6-year-old boy.
      CASE REPORT: A 6-year-old male patient was admitted to the hospital with chief
      complaint of ptosis and engorgement of the left eyelid for 50 days. A 4 x 10-cm
      bony protuberance of the left temporal region with hemangiectasia was observed to
      beat with pulse without vascular murmur. computed tomographic angiography (CTA)
      showed two saccular aneurysms of the left internal carotid artery. The first one
      which was about 3 cm in length and 2 cm in maximum diameter was located in the
      middle of the petrous portion (including parts of C2 and C3). The second one
      which was about the same size was located from the middle of the cavernous
      portion to the upper end of the left internal carotid artery. Computed tomography
      showed an arachnoid cyst in the left temporal region and abnormality of the left
      temporal bone. According to the specific circumstances of this patient, we
      believe that surgical treatment is rather risky and the loss might outweigh the
      gain. Therefore, we suggested to the parents that the child should be followed up
      for the coming years for monitoring and possible treatment. DISCUSSION: Multiple
      saccular aneurysms of extracranial and intracranial internal carotid artery in
      children are extremely rare. According to this case, the child had congenital
      bony protuberance of the left temporal region with hemangiectasia, which made
      this case particularly specific. Besides all those discovered abnormalities, this
      child was a healthy boy. Due to the difficulty and high risk of possible surgical
      treatment, we suggested that no further treatment be performed at the moment and
      the child should be followed up for a long period of time. Worthy examinations
      such as CT, CTA, and MRI are recommended for reviewing the development of
      aneurysms and CNS of this boy. Further treatment might be performed in the
      future. We welcome all forms of discussion about this case and similar cases
      around the globe.

PMID- 19763590
TI  - A differential diagnosis to "growing lipoma".

PMID- 19763591
TI  - Hydrocephalus and Chiari type 1 malformation in macrocephaly-cutis marmorata
      telangiectatica congenita: a case-based update.
AB  - BACKGROUND: Macrocephaly-cutis marmorata telangiectatica congenita (M-CMTC) is a
      newly described condition characterized by macrocephaly (megalencephaly), cutis
      marmorata telangiectatica congenita, macrosomia and/or asymmetric growth, central
      nervous system abnormalities and neurological manifestations. DISCUSSION: This
      condition is usually documented in the Genetics' literature but it has been
      scarcely disseminated among neurosurgeons. Sudden death of uncertain origin has
      been reported in children with M-CMTC. Hydrocephalus and tonsillar herniation
      often occur in this syndrome. The appearance of symptoms and signs of
      intracranial hypertension or of brain stem compression in M-CMTC patients may
      herald the development of irreversible neurological damage or death. ILLUSTRATIVE
      CASES: We report two children diagnosed with M-CMTC and hydrocephalus who were
      given a ventriculo-peritoneal shunt. In addition, one of them exhibited tonsillar
      herniation. CONCLUSIONS: Given the high incidence of hydrocephalus and/or
      tonsillar herniation that occurs in M-CMTC, serial neuroimaging studies and
      neurosurgical referral seem to be warranted in children with this syndrome.

PMID- 19763592
TI  - Craniocerebral gunshot injuries in preschoolers.
AB  - INTRODUCTION: Gunshot wounds (GSW) to the head are the most lethal form of
      trauma; unfortunately, the frequency of children being involved in such form of
      trauma is increasing at an alarming rate worldwide. We present our experience
      with four children from 2 to 3 years of age with craniocerebral GSW admitted to
      the neurosurgery service at a tertiary care hospital. METHODS: For this study,
      four children, 2 to 3 years old, injured solely from bullet injuries to the head
      were selected. Their history, arrival Glasgow Coma Scale (GCS), clinical
      presentation at the time of arrival in ER, radiological findings, management, and
      follow-up reviewed. RESULTS: Out of four children, only one did not survive. The
      bullet entrance wound was in the parietal region in robbery-related incidences,
      and, in three cases, the injury was bihemispheric. The time taken to reach the
      emergency department was less than 2 h for all patients except one. Of four
      patients, three presented with GCS between 3 and 5 while 1 presented with GCS
      well above ten. CONCLUSION: Our results show that even in children presenting
      with low GCS<5, an early act of aggressive surgical intervention can prove to be
      a life-saving measure.

PMID- 19763593
TI  - The cuprizone animal model: new insights into an old story.
AB  - Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease that
      affects the central nervous system and represents the most common neurological
      disorder in young adults in the Western hemisphere. There are several well
      characterized experimental animal models that allow studying potential mechanisms
      of MS pathology. While experimental allergic encephalomyelitis is one of the most
      frequently used models to investigate MS pathology and therapeutic interventions,
      the cuprizone model reflects a toxic experimental model. Cuprizone-induced
      demyelination in animals is accepted for studying MS-related lesions and is
      characterized by degeneration of oligodendrocytes rather than by a direct attack
      on the myelin sheet. The present article reviews recent data concerning the
      cuprizone model and its relevance for MS. Particular focus is given to the
      concordance and difference between human MS patterns (types I-IV lesions) and
      cuprizone-induced histopathology, including a detailed description of the
      sensitive brain regions extending the observations to different white and grey
      matter structures. Similarities between pattern III lesions and cuprizone-induced
      demyelination and dissimilarities, such as inflamed blood vessels or the presence
      of CD3+ T cells, are outlined. We also aim to distinguish acute and chronic
      demyelination under cuprizone including processes such as spontaneous
      remyelination during acute demyelination. Finally, we point at strain and gender
      differences in this animal model and highlight the contribution of some growth
      factors and cytokines during and after cuprizone intoxication, including LIF, IGF
      1, and PDGFalpha.

PMID- 19763595
TI  - Identification of polymorphisms in the Toll-like receptor gene and the
      association with allergic rhinitis.
AB  - The TLRs gene encodes the principal innate immunity receptor in humans. The TLR2
      Arg753Gln and Arg677Trp polymorphisms have been associated with a reduced
      response of monocytes and cell lines to challenge with mycobacteria. The TLR4
      Asp299Gly and Thr399Ile polymorphisms have been associated with a reduction in
      the inflammatory responses to lipopolysaccharide in humans. It has been suggested
      that TLR2 and TLR4 polymorphisms may be associated with allergic responses; thus,
      we hypothesized that TLR2 and TLR4 polymorphisms may modify the relative risk for
      development of allergic rhinitis. The Taqman assay and high-resolution melt (HRM)
      were used for genotyping. We analyzed two single nucleotide polymorphisms (SNPs;
      597T>C and 1350T>C) in the TLR2 gene and 1 SNP (4216G>C) in the TLR4 gene. We
      compared the genotype of these SNPs in patients with allergic rhinitis and
      controls without allergic rhinitis. We also estimated the haplotype frequencies
      between the two groups. The genotype and allele frequencies of the 597T>C and
      1350T>C SNPs in the TLR2 gene were not significantly different between the
      patients with allergic rhinitis and controls (P > 0.05). The genotype and allele
      frequencies of 4216G>C in the TLR4 gene were not significantly different between
      the patients with allergic rhinitis and controls (P > 0.05). Haplotype analysis
      of the following two different (597)-(1350) major haplotypes (frequency >0.05)
      were present in the TLR2 gene: T-C and C-C. The C-C haplotype was positively
      associated with allergic rhinitis (P = 0.048). Our study suggests that the TLR2
      gene polymorphisms might be susceptible to the development of allergic rhinitis.
      Further functional studies of TLR2 genetics in light of the associations with
      allergic rhinitis inflammation would help clarify the role of TLR2 genetics in
      clinical evaluations.

PMID- 19763596
TI  - Is routine histopathological examination of FESS material useful?
AB  - Analysis of the clinical value of histopathological examination of material
      collected during functional endoscopic sinus surgery. Retrospective analysis of
      collected data of patients undergoing functional endoscopic sinus surgery over a
      7-year period. Data were collected from a pathology database of the Sint Lucas
      Andreas Hospital, Amsterdam, The Netherlands. All material collected from 1,944
      functional endoscopic sinus surgery cases in 1,695 patients (some patients
      underwent revision surgery) operated between 2000 and 2007 was examined
      histologically. Patients with a histological outcome different from chronic
      inflammation or polyposis nasi, were checked on indication of surgery, type of
      surgery and preoperative clinical suspicion for (pre)malignancy. The impact of
      the histological diagnosis on the clinical course was evaluated. Thirty-seven
      unusual diagnoses were reported: 18 cases of inverted papilloma, one squamous
      cell carcinoma, two malignant lymphomas, one leiomyosarcoma, eight squamous cell
      papillomas, one Churg Strauss syndrome, one Schneiderian papilloma, two cases of
      Wegener's granulomatosis and three cases of sarcoidosis. All other specimens were
      identified as chronic inflammation and/or nasal polyposis. Only two clinically
      significant, unexpected diagnoses, both inverted papilloma, have resulted from
      the histological investigation. We conclude that the close correlation between
      histopathology outcome and examination on clinical grounds or gross inspection
      indicates that routine histopathological examination of functional endoscopic
      sinus surgery material has little clinical value and it is questionable if this
      should be performed. In patients in whom there is a high degree of suspicion for
      (pre)malignancy, histopathological examination of functional endoscopic sinsus
      surgery material remains indicated.

PMID- 19763597
TI  - Management of parotid gland surgery in a university teaching hospital.
AB  - The aim of our study was the evaluation of two controversial procedures used in
      surgical management of parotid tumours in a university teaching hospital: fine
      needle aspiration cytology (FNAC) and continuous operative facial monitoring with
      nerve integrity monitor (NIM). We present a retrospective study of 96 consecutive
      cases of parotid gland surgical procedures, performed in our department of ENT
      Surgery (Bichat University Hospital) during a 2-year period. After the exclusion
      of nine patients (4 recurrent tumours, 3 insufficient data and 2 obviously
      malignant tumours with preoperative facial paralysis and necessary peroperative
      facial nerve sacrifice), the final group included 40 men and 47 women (mean age
      46 years). FNAC, final histological diagnosis, NIM use, postoperative facial
      disorders and operative time were analysed. Other variables included age, sex,
      type of surgery and other postoperative complications. FNAC: 78 patients
      underwent FNAC. Positive predictive value for malignancy was 100%; negative
      predictive value 94.4%; sensitivity 63.6%; specificity 100%. NIM: surgery was
      performed without NIM for 41 patients, with for 46 patients. There was no
      significant difference in occurrence of facial disorders between the two groups.
      Operative time was significantly lower in group operated with NIM for
      extracapsular dissection, superficial parotidectomy and total parotidectomy.
      Because continuous efforts of modern health systems to improve operating room
      schedules may threaten resident surgeons training, using NIM and performing
      preoperative FNAC may help operative planning and improve medical education in a
      teaching hospital.

PMID- 19763598
TI  - The NEI VFQ-25 vision-related quality of life and prevalence of eye disease in a
      working population.
AB  - PURPOSE: To apply the National Eye Institute 25-item Visual Function
      Questionnaire (VFQ-25) to a large group of working people and assess the
      prevalence of eye disease. METHODS: In this cross-sectional study, 619 employees
      of two large enterprises in Munich, Germany, underwent complete ophthalmological
      examination and assessment of the vision-related quality of life by the Visual
      Function Questionnaire (VFQ-25, German translation). Statistical analysis
      including binary logistic regression to investigate predictive factors of eye
      disease was performed. RESULTS: The age of the participants was mean 42 years. In
      108 patients (17.4%) an ophthalmological disease was present. The mean VFQ-25
      composite score was 91.1, and was not significantly different between the group
      with (88.8) or without (91.6) eye disease. A clear age dependency of VFQ-25
      scores was seen. Most reduced subscales in eye disease were ocular pain and role
      difficulties. Patients with amblyopia did not show any reduction in visual
      quality of life (composite score 93.4). In the binary regression model,
      considering the clinical parameters intraocular pressure (IOP), cup/disc ratio
      (CDR), and spherical equivalent, as well as some of the VFQ-25 subscales, the
      presence of eye disease could be predicted with a high specificity of 98.7% but a
      low sensitivity of 12.2%. CONCLUSIONS: Normal values of the VFQ-25 performance in
      a large number of working people in Germany are given with a clear age
      dependency. A combination of refraction, IOP, CDR and some VFQ subscales could
      reasonably well exclude any prevalent eye disease. For screening purposes,
      neither variable nor combination was sufficiently sensitive and specific.

PMID- 19763599
TI  - Reduced-serum vitamin C and increased uric acid levels in normal-tension
      glaucoma.
AB  - BACKGROUND: Vitamin A, B(9), C, E, and uric acid are well-known antioxidants and
      may prevent age-related eye disorders. The aim of the present study was to
      investigate the levels of antioxidant vitamins, A, B(9), C, E, and antioxidative
      substance, uric acid in the serum of Japanese patients with normal-tension
      glaucoma and compare the results with normal controls. METHODS: All subjects with
      suspicion of primary open-angle glaucoma who came to the glaucoma subspeciality
      clinic of Keio University Hospital were enrolled in this study. Sixty patients
      (28 males, 32 females; mean age +/- standard deviation: 59.9 +/- 9.8 years) with
      newly diagnosed primary open-angle glaucoma patients were consecutively enrolled
      in this study. After the diagnosis of primary open-angle glaucoma, the patients
      underwent 24-h IOP measurements. Forty-seven newly diagnosed consecutive normal
      tension glaucoma patients (18 males, 29 females; mean age +/- standard deviation:
      59.5 +/- 10.2 years) were enrolled in this study. The control subjects were
      recruited from subjects who came to the clinic for annual refractive check-up.
      The 44 consecutive control subjects of the current study, (16 males, 28 females;
      62.7 +/- 14.8 years) did not have any ocular diseases. The serum levels of
      vitamins A, B(9), C, E, and uric acid were measured. The values were compared
      between the normal-tension glaucoma and control groups by the Mann-Whitney U
      test. RESULTS: Serum levels of vitamin C were significantly lower in normal
      tension glaucoma patients than in normal healthy controls (P = 0.04; normal
      tension glaucoma; 4.6 +/- 4.0 microg/ml control; 6.3 +/- 3.9 microg/ml). Uric
      acid level was significantly higher in normal-tension glaucoma patients than in
      controls (P = 0.01; normal-tension glaucoma; 5.8 +/- 1.5 mg/dl control; 4.9 +/-
      1.4 mg/dl). No statistically significant difference was seen in vitamin A (P =
      0.41; normal-tension glaucoma; 82.1 +/- 26.7 microg/dl control; 77.1 +/- 30.1
      microg/dl), B(9) (P = 0.37; normal-tension glaucoma; 8.7 +/- 4.3 ng/ml control;
      8.0 +/- 3.1 ng/ml)and E (P = 0.83; normal-tension glaucoma; 1.5 +/- 0.6 control;
      1.5 +/- 0.6) levels between normal-tension glaucoma and control groups.
      CONCLUSION: Normal-tension glaucoma patients had lower serum levels of vitamin C
      and increased levels of uric acid. These observations may pave the way for
      possible alternative treatment for normal-tension glaucoma.

PMID- 19763600
TI  - A comparative clinical study of the visual results between three types of
      multifocal lenses.
AB  - PURPOSE: To compare the patients' visual results after bilateral implantation of
      the multifocal intraocular lenses (MIOLs): ReZoom (NXG1, Abbott Medical Optics,
      Abbott Park, IL, USA), Acrysof ReSTOR (SA60D3, Alcon Laboratories, Fort Worth,
      TX, USA) and Tecnis MF (ZM900, Abbott Medical Optics). MATERIALS AND METHODS: A
      prospective, nonrandomized, comparative trial of 30 patients (60 eyes) aged 46-71
      (mean age 56.3 +/- 5.96) divided into three equal groups with implanted
      bilaterally multifocal lenses: ReZoom IOL, Acrysof ReSTOR IOL and Tecnis MF IOL.
      The patient selection criteria included no other eye disease besides cataract,
      and corneal astigmatism of 1.5 diopters or less. In each case, the patients were
      scheduled to have standard phacoemulsification surgery with IOL implantation into
      the bag. The postoperative target was emmetropia. The mean follow-up was 6 months
      in all eyes. The following parameters were assessed/carried out: slit-lamp
      examination, uncorrected and best spectacle-corrected far and near visual acuity,
      autorefractometry, intraocular pressure, contrast sensitivity and subjective
      satisfaction with vision using the VF-14 survey. RESULTS: After surgery, all eyes
      were within +/-2.0D of target refraction. The mean uncorrected distance visual
      acuity improved in all cases. The postoperative BCDVA was better than 20/30 at
      the sixth month in all eyes. Six months postoperatively, the mean uncorrected
      distance visual acuity (UCDVA) +/- standard error (SE) in the ReZoom, ReSTOR and
      Tecnis MF groups was 0.11 +/- 0.01, 0.17 +/- 0.02 and 0.14 +/- 0.02 (LogMAR)
      respectively. All results were significantly better compared to preoperative
      values (p < 0.001) but did not differ between the study groups (p > 0.05). At the
      final visit, 75% of eyes in the ReZoom group achieved J1 (Jaeger standard) in
      comparison to 85% in the ReSTOR and Tecnis MF groups. Eighty percent of patients
      with bilaterally implanted ReSTOR and Tecnis MF IOL were spectacle-independent,
      in comparison to 70% with implanted ReZoom IOL. Thirty percent of patients with
      implanted Rezoom and Acrysof Restor IOL and 20% with implanted Tecnis multifocal
      IOL reported little or moderate halo and glare. The patients' satisfaction after
      the procedure was excellent; the scoring on the VF-14 survey ranged from 70-100%,
      with an average of 93%. No patient was dissatisfied with the results of the
      surgery. CONCLUSIONS: The implantation of tested multifocal intraocular lenses
      provides good near and distance visual acuity. We did not observe any
      statistically significant differences between the tested multifocal intraocular
      lenses with regard to best-corrected distance visual acuity, presence of glare
      and halo, as well as satisfaction with vision.

PMID- 19763601
TI  - Predictive factors for changes in macular edema in intravitreal bevacizumab
      therapy of retinal vein occlusion.
AB  - BACKGROUND: To evaluate prognostic factors of response to intravitreal
      bevacizumab therapy of macular edema (ME) due to central retinal vein occlusion
      (CRVO) or branch retinal vein occlusion (BRVO). METHODS: Patients with ME due to
      CRVO (32 patients) or BRVO (38 patients) received intravitreal bevacizumab (2.5
      mg/0.1 ml) at baseline, and every 6 to 8 weeks if OCT showed persistent or
      recurrent ME. Visual acuity (EDTRS), ophthalmic examination and OCT were
      performed at baseline and at all follow-up visits. Six to 8 weeks after first
      injection, baseline factors (visual acuity, central retinal thickness, age and
      gender) were analyzed retrospectively between patients with resolved ME (group 1)
      and persisting ME (group 2). At last visit, baseline factors of patients with
      resolved ME since first injection (group A), with recurrent ME since baseline
      (group B) and with persistent ME since baseline (group C) were compared. RESULTS:
      In CRVO patients, central retinal thickness (CRT) and patients' age are
      prognostic predictors in bevacizumab therapy. Age of CRVO patients differed
      significantly between groups 1 and 2 after first injection, while CRT only showed
      a strong trend to thinner CRT. At last visit, age and CRT differed statistically
      significantly between groups A, B and C. In BRVO patients, none of the
      investigated factors revealed any prognostic value. In CRVO and BRVO patients,
      final CRT is correlated with the CRT after first injection. CONCLUSION: CRT and
      age of patients have prognostic value in bevacizumab therapy of ME due to CRVO.
      CRVO patients who benefit from therapy are significantly younger and have a lower
      CRT at baseline than patients with persisting ME. In BRVO patients, no predictive
      factors for effectiveness of bevacizumab therapy could be observed.

PMID- 19763602
TI  - Caudate lobe resection: an Egyptian center experience.
AB  - BACKGROUND DATA: Hepatectomy is a technically challenging surgery, and of all
      aspects of hepatic resection, caudate lobe resection is the most difficult.
      Knowledge of the anatomy of the caudate lobe is necessary to achieve safe caudate
      lobe resection. METHODOLOGY: Hospital records of 54 patients, who had caudate
      lobe resection in our center from January 2000 to August 2007, were retrieved.
      The demographic data, clinicopathological features, and perioperative events were
      extracted and analyzed. RESULTS: Out of a total of 500 patients who had various
      forms of hepatic resection during the period in question, only 54 had caudate
      lobe resection (10.8%). Isolated caudate lobe resection (ICLR) was performed in
      16 (29.6%) patients while the remainder had caudate lobe resection as a part of a
      major hepatectomy. Indications for hepatectomy in patients with ICLR include
      hepatocellular carcinoma, primary hepatic carcinoid tumor, cavernous hemangioma,
      and adenoma. Mean operative time for ICLR was 230 +/- 50 min while it was 240 +/-
      50 min for right hepatectomy and 245 +/- 55 min for left hepatectomy. The
      associated mean blood loss was 1200 +/- 200, 1300 +/- 350, and 1350 +/- 350 ml,
      respectively. None of these were statistically significant. In patients who had
      ICLR, there was no mortality while three patients developed postoperative
      complications (bile leak in two patients and one patient with wound infection).
      Various forms of perioperative complications were noticed in six patients. All
      these patients, who also showed 7.8% mortality, had major hepatectomy.
      CONCLUSIONS: Caudate lobe resection is a technically challenging procedure.
      Isolated caudate lobe resection is a safe procedure with good outcome in well
      selected patients. It is, however, associated with increased perioperative risks
      when associated with major hepatectomy.

PMID- 19763603
TI  - Multiple primary malignancies involving colorectal cancer--clinical
      characteristics and prognosis with reference to surveillance.
AB  - BACKGROUND/AIM: The purpose of this study was to investigate clinically useful
      information for effective screening for synchronous and metachronous second
      primary cancers and to suggest potential surveillance tool. METHODS: We
      retrospectively reviewed 1,063 patients who were treated with potentially
      curative surgery for colorectal cancer at Gachon University, Gil Hospital from
      1997 to 2007. RESULTS: The incidence of synchronous or metachronous cancer in
      addition to colorectal cancer was 5.3% (57 patients). The most common second
      primary cancer was stomach (54.3%), followed by cancers in cervix (12.2%). The
      time interval between the first and second tumor in colorectal cancer associated
      with metachronous extracolonic malignancy ranged from 1.1 to 10.8 years. The
      incidence of early-stage tumor was higher in patients with synchronous cancer
      than in those with a metachronous cancer with statistical significance (p =
      0.034). The 5-year survival rate of the colorectal cancer group without second
      primary cancer was 70.1%, whereas that for the second primary cancer group was
      63.8% (p = 0.253). The 5-year survival rate of the colorectal cancer group with
      stomach cancer was 70.5%, whereas that for the second primary cancer other than
      stomach cancer group was 56.6% (p = 0.282). CONCLUSION: The frequent association
      between colorectal cancer and gastric cancer suggests an inclusion of
      gastrofiberscope when surveillancing patients with colorectal cancer in Korean
      population. Second primary cancers may develop even 10 years after the initial
      operation; thus, a need for lifelong surveillance even more than 5 years may be
      necessary.

PMID- 19763604
TI  - Effects of a clinical pathway on quality of care in kidney transplantation: a non
      randomized clinical trial.
AB  - PURPOSE: Standardization of care is essential for improving outcome of kidney
      transplantation (KT). Clinical pathways (CPs) are known to standardize and
      improve perioperative care for a number of interventions. In transplantation
      medicine, however, pertinent evidence is very limited. This study evaluates
      effects of a CP on quality of care in KT. MATERIALS AND METHODS: Consecutive
      patients (n=32) undergoing KT between July 2006 and August 2007 who were treated
      with a CP were compared to patients (n=44) treated without CP between January
      2005 and June 2006. Several quality indicators regarding process and outcome were
      compared between groups. RESULTS: Quality of care was significantly higher in the
      CP group for the following indicators: timely removal of central venous
      catheters, wound drains, and Foley catheters and control of cyclosporine levels,
      respiratory exercising, and pain control. Median stay decreased non-significantly
      from 21.4 to 18.3 days. There was significantly less delayed graft function in
      the CP group. All other outcome indicators showed no significant differences.
      CONCLUSIONS: Implementation of a CP for KT improves the quality of perioperative
      treatment by standardizing care. Regarding effects on outcome, no clear
      conclusion can be drawn. We recommend that large randomized studies are conducted
      to evaluate the latter issue.

PMID- 19763605
TI  - Multiple effects of 4-aminopyridine on feline and rabbit sinoatrial node myocytes
      and multicellular preparations.
AB  - 4-aminopyridine (4-AP) is commonly used to block the transient outward potassium
      current, I(to), in cardiac and noncardiac tissues. In the present work, we found
      that 4-AP inhibited the rapid component of the delayed rectifier potassium
      current, I(Kr), in rabbit-isolated sinoatrial node myocytes by 25% (1 mM) and 51%
      (5 mM) and inhibited the slow component of the delayed rectifier potassium
      current, I(Ks), in cat- isolated sinoatrial node myocytes by 39% (1 mM) and 62%
      (5 mM). In cat- and rabbit-isolated sinoatrial node myocytes, 4-AP activated
      muscarinic receptors in a voltage-dependent manner to increase the acetylcholine
      activated potassium current, I(KACh). In multicellular preparations of the
      central region of the sinoatrial node from nonreserpinized rabbits, 4-AP produced
      an increase in action potential overshoot, frequency, and rate of diastolic
      depolarization. In the presence of the beta-adrenergic antagonist propranolol, 4
      AP produced a marked increase in duration and a marked decrease in maximum
      diastolic potential and eventually, cessation of the spontaneous activity in
      preparations from the sinoatrial central region. In multicellular preparations
      from reserpinized rabbits, 4-AP produced similar effects to those observed in the
      presence of propranolol. We conclude that 4-AP inhibits multiple cardiac K(+)
      currents, including I(to), I(Kr), and I(Ks), and that these activities mask
      I(KACh) activation. In addition, in multicellular preparations, 4-AP produces
      neurotransmitter release from the autonomic nerve terminals. These multiple
      effects need to be considered when using 4-AP as a "specific" I(to) blocker.

PMID- 19763606
TI  - Anionic phospholipids differentially regulate the epithelial sodium channel
      (ENaC) by interacting with alpha, beta, and gamma ENaC subunits.
AB  - Anionic phospholipids (APs) present a variety of lipids in the cytoplasmic
      leaflet of the plasma membrane, including phosphatidylinositol (PI), PI-4
      phosphate (PI(4)P), phosphatidylserine (PS), PI-4,5-bisphosphate (PI(4,5)P(2)),
      PI-3,4,5-trisphosphate (PI(3,4,5)P(3)), and phosphatidic acid (PA). We previously
      showed that PI(4,5)P(2) and PI(3,4,5)P(3) upregulate the renal epithelial sodium
      channel (ENaC). Further studies from others suggested that PI(4,5)P(2) and
      PI(3,4,5)P(3) respectively target beta- and gamma-ENaC subunit. To determine
      whether PI(4,5)P(2) and PI(3,4,5)P(3) selectively bind to beta and gamma subunit,
      we performed lipid-protein overlay experiments. Surprisingly, the results reveal
      that most APs, including PI(4)P, PS, PI(4,5)P(2), PI(3,4,5)P(3), and PA, but not
      PI, non-selectively bind to not only beta and gamma but also alpha subunit. To
      determine how these APs regulate ENaC, we performed inside-out patch-clamp
      experiments and found that PS, but not PI or PI(4)P, maintained ENaC activity,
      that PI(4,5)P(2) and PI(3,4,5)P(3) stimulated ENaC, and that PA, however,
      inhibited ENaC. These data together suggest that APs differentially regulate ENaC
      by physically interacting with alpha-, beta-, and gamma-ENaC. Further, the data
      from cell-attached patch-clamp and confocal microscopy experiments indicate that
      PA, a product of phospholipase D, may provide one of the pathways for inhibition
      of ENaC by endothelin receptors.

PMID- 19763607
TI  - Gene variants as determinants of longevity: focus on the inflammatory factors.
AB  - Human longevity is an extremely complex trait with various genetic, epigenetic
      and environmental factors acting upon the longevity phenotype. It is now becoming
      evident that whilst the genetic differences contribute only modestly to life
      expectancy before the age of 60 years, their impact on survival becomes more
      prominent at the extreme ages. Several longevity gene candidates have emerged
      during the past decade; the majority of them are related either to inflammatory
      functions, stress response or to lipid and glucose metabolism. The variants of
      inflammatory and immune response genes are of special interest since advancing
      ages is accompanied by a decline in several immune functions--a phenomenon called
      immunosenescence. Paradoxically, ageing is also characterised by chronic low
      grade inflammation termed "inflammaging", which manifests as a two- to fourfold
      increase in the production of proinflammatory cytokines and acute phase proteins.
      These contrasting phenomena provide a functional rationale of how the genetic
      differences in inflammatory mediators may modify the life span of the elderly.
      Besides describing the pre-existing inflammatory and immune-related longevity
      gene variants, in this review, we also explain some of the theoretical and
      practical challenges that genetic longevity studies often encounter.

PMID- 19763608
TI  - Angiotensin receptors as determinants of life span.
AB  - Angiotensin II (Ang II), the central product of renin-angiotensin system, has a
      role in the etiology of hypertension and in pathophysiology of cardiac and renal
      diseases in humans. Other functions of Ang II include effects on immune response,
      inflammation, cell growth and proliferation, which are largely mediated by Ang II
      type 1 receptor (AT(1)). Several experimental studies have demonstrated that Ang
      II acts through AT(1) as a mediator of normal aging processes by increasing
      oxidant damage to mitochondria and in consequences by affecting mitochondrial
      function. Recently, our group has demonstrated that the inhibition of Ang II
      activity by targeted disruption of the Agtr1a gene encoding Ang II type 1A
      receptor (AT(1A)) in mice translates into marked prolongation of life span. The
      absence of AT(1A) protected multiple organs from oxidative damage and the
      alleviation of aging-like phenotype was associated with increased number of
      mitochondria and upregulation of the prosurvival gene sirtuin 3. AT(1) receptor
      antagonists have been proven safe and well-tolerated for chronic use and are used
      as a key component of the modern therapy for hypertension and cardiac failure,
      therefore Ang II/AT(1) pathway represents a feasible therapeutic strategy to
      prolong life span in humans.

PMID- 19763609
TI  - Senescence and life span.
AB  - Senescence is a general cellular process that occurs as a response to stress and
      damage. It forms an alternative response of cells to damage that might otherwise
      cause programmed cell death. Whereas telomere shortening leading to telomere
      dysfunction was the first described cause of senescence, it is now known that
      senescence can result from many sources of damage. Senescent cells are found in
      tissues in vivo, but the cause of senescence in these cells is mostly unknown. In
      many cases, senescence may be the result of the action of activated oncogenes in
      cells. By preventing activated oncogenes from initiating a clone of neoplastic
      cells, senescence acts as a protective mechanism against cancer development.
      Until recently, the fate of senescent cells in vivo was unknown, but new evidence
      indicates that they are cleared by components of the innate immune system. In
      this way, senescence and apoptosis act as parallel pathways by which severely
      damaged cells are eliminated from the body. Some senescent cells persist in
      tissues, in some cases increasing in frequency as a function of age. It is
      hypothesized that these persistent senescent cells have adverse effects on tissue
      function. If so, senescence may be an example of antagonistic pleiotropy,
      providing an anticancer mechanism in early life but having adverse effects on
      tissue function in late life. Much more research is needed to address the broader
      question of the overall impact of senescence on life span.

PMID- 19763610
TI  - The tissue-specific expression of TRPML2 (MCOLN-2) gene is influenced by the
      presence of TRPML1.
AB  - Mucolipidosis type IV is a lysosomal storage disorder caused by the loss or
      dysfunction of the mucolipin-1 (TRPML1) protein. It has been suggested that
      TRPML2 could genetically compensate (i.e., become upregulated) for the loss of
      TRPML1. We thus investigated this possibility by first studying the expression
      pattern of mouse TRPML2 and its basic channel properties using the varitint
      waddler (Va) model. Here, we confirmed the presence of long variant TRPML2
      (TRPML2lv) and short variant (TRPML2sv) isoforms. We showed for the first time
      that, heterologously expressed, TRPML2lv-Va is an active, inwardly rectifying
      channel. Secondly, we quantitatively measured TRPML2 and TRPML3 mRNA expressions
      in TRPML1-/- null and wild-type (Wt) mice. In wild-type mice, the TRPML2lv
      transcripts were very low while TRPML2sv and TRPML3 transcripts have predominant
      expressions in lymphoid and kidney organs. Significant reductions of TRPML2sv,
      but not TRPML2lv or TRPML3 transcripts, were observed in lymphoid and kidney
      organs of TRPML1-/- mice. RNA interference of endogenous human TRPML1 in HEK-293
      cells produced a comparable decrease of human TRPML2 transcript levels that can
      be restored by overexpression of human TRPML1. Conversely, significant
      upregulation of TRPML2sv transcripts was observed when primary mouse lymphoid
      cells were treated with nicotinic acid adenine dinucleotide phosphate, or N-(2-[p
      bromocinnamylamino]ethyl)-5-isoquinoline sulfonamide, both known activators of
      TRPML1. In conclusion, our results indicate that TRPML2 is unlikely to compensate
      for the loss of TRPML1 in lymphoid or kidney organs and that TRPML1 appears to
      play a novel role in the tissue-specific transcriptional regulation of TRPML2.

PMID- 19763611
TI  - Consciousness as recursive, spatiotemporal self-location.
AB  - At the phenomenal level, consciousness arises in a consistently coherent fashion
      as a singular, unified field of recursive self-awareness (subjectivity) with
      explicitly orientational characteristics--that of a subject located both
      spatially and temporally in an egocentrically-extended domain. Understanding
      these twin elements of consciousness begins with the recognition that ultimately
      (and most primitively), cognitive systems serve the biological self-regulatory
      regime in which they subsist. The psychological structures supporting self
      located subjectivity involve an evolutionary elaboration of the two basic
      elements necessary for extending self-regulation into behavioral interaction with
      the environment: an orientative reference frame which consistently structures
      ongoing interaction in terms of controllable spatiotemporal parameters, and
      processing architecture that relates behavior to homeostatic needs via feedback.
      Over time, constant evolutionary pressures for energy efficiency have encouraged
      the emergence of anticipative feedforward processing mechanisms, and the
      elaboration, at the apex of the sensorimotor processing hierarchy, of self
      activating, highly attenuated recursively-feedforward circuitry processing the
      basic orientational schema independent of external action output. As the primary
      reference frame of active waking cognition, this recursive self-locational schema
      processing generates a zone of subjective self-awareness in terms of which it
      feels like something to be oneself here and now. This is consciousness-as
      subjectivity.

PMID- 19763612
TI  - Splenic micronodular T-cell/histiocyte-rich large B-cell lymphoma: effect of
      prior corticosteroid therapy.
AB  - We report on three patients who were treated with corticosteroids only prior to
      the diagnosis of splenic lymphoma. Corticosteroids were administered for
      different conditions, at different doses, and for various periods of time. The
      primary diagnosis was splenic micronodular T-cell/histiocyte-rich large B-cell
      lymphoma in the three cases, and it was reached with variable difficulty. We
      suggest that the corticosteroid treatment was one of the causes for the
      complications in reaching a diagnosis. The morphologic appearance of the
      microscopic splenic nodules was the most variable feature and may possibly
      reflect the dose and duration of the corticosteroid therapy. However, the
      histopathologic changes are probably not related with Epstein-Barr virus-induced
      immunosuppression.

PMID- 19763613
TI  - CpG island hypermethylation and repetitive DNA hypomethylation in premalignant
      lesion of extrahepatic cholangiocarcinoma.
AB  - Biliary intraepithelial neoplasia (BilIN) is the premalignant lesion of
      extrahepatic cholangiocarcinoma (EHC), and there are no published data regarding
      epigenetic changes throughout disease progression from normal biliary epithelia
      to BilIN to EHC. The objective of this study was to identify the occurrence of
      CpG island hypermethylation and repetitive DNA hypomethylation in BilIN. A total
      of 50 EHCs, 31 BilINs, and 31 normal cystic duct samples were analyzed for their
      methylation status in seven genes and two repetitive DNA elements. The number of
      methylated genes increased with disease progression (normal bile duct, 0.6;
      BilIN, 2.0; EHC, 3.6; P < 0.001). The methylation level of examined genes was
      significantly higher in BilIN than in normal samples (TMEFF2, HOXA1, NEUROG1, and
      RUNX3, P < 0.05) and in EHC than in BilIN samples (TMEFF2, HOXA1, NEUROG1, RUNX3,
      RASSF1A, and APC, P < 0.05). Long interspersed nucleotide element-1 (LINE-1) and
      juxtacentromeric satellite 2 (SAT2) methylation levels were markedly lower in EHC
      than in normal duct and BilIN samples, and BilIN samples showed a decrease of
      SAT2 methylation levels but no decrease of LINE-1 methylation levels compared to
      normal samples. These findings suggest that most of cancer-specific CpG island
      hypermethylation occur in the stage of BilIN and that CpG island hypermethylation
      seems to occur earlier than repetitive DNA element hypomethylation.

PMID- 19763614
TI  - p16 INK4 and CEA can be mutually exchanged with confidence between both relevant
      three-marker panels (ER/Vim/CEA and ER/Vim/p16 INK4) in distinguishing primary
      endometrial adenocarcinomas from endocervical adenocarcinomas in a tissue
      microarray study.
AB  - The accurate distinction between primary endocervical adenocarcinomas (ECA) and
      endometrial adenocarcinomas (EMA) may require the use of multiple ancillary
      monoclonal antibodies in panels of immunohistochemistry stains. In addition to
      reappraising the expressions of four commonly used individual monoclonal
      antibodies [estrogen receptor (ER), Vimentin (Vim), carcinoembryonic antigen
      (CEA), and p16(INK4)], this study was designed to investigate whether CEA and
      p16(INK4) can be effectively exchanged between two relevant three-marker panels
      (ER/Vim/CEA vs. ER/Vim/p16(INK4)) in distinguishing ECA from EMA. A tissue
      microarray was constructed using paraffin-embedded, formalin-fixed tissues from
      35 hysterectomy specimens, including 14 ECA and 21 EMA. Utilizing the avidin
      biotin technique, tissue array sections were immunostained with the four
      aforementioned individual markers (ER, Vim, CEA, and p16(INK4)). In addition to
      the four individual monoclonal antibodies, both their respective three-marker
      panels, proposed here, showed statistically significant (p < 0.05) frequency
      differences between these two gynecologic tumors (ECA vs. EMA). The panel
      performance and test effectiveness revealed that both three-marker panels are
      promising and very helpful. According to our data, when histomorphological and
      clinical doubt exists as to the primary site of origin, we recommend using either
      of these two conventional three-marker panels, which consist of ER/Vim/CEA and
      ER/Vim/p16(INK4). CEA and p16(INK4) can be interchanged with confidence without
      significantly influencing the panel presentations and efficiencies in
      distinguishing between adenocarcinomas of endocervical and endometrial origin.

PMID- 19763615
TI  - Further immunohistochemical characterization of BRD1 a new susceptibility gene
      for schizophrenia and bipolar affective disorder.
AB  - We have recently shown that the gene BRD1 is associated with schizophrenia and
      bipolar affective disorder and that the BRD1 protein (BRD1) which is expressed in
      neurons may occur in a short and a long variant. The aim of the study was to
      generate polyclonal antibodies against new BRD1 epitopes enabling discrimination
      between the long and short BRD1 variants, and elucidate the BRD1 distribution in
      several human tissues, including the CNS. Polyclonal rabbit antibodies were
      raised against three different BRD1 epitopes. One (67) was specific for the long
      BRD1 variant, whereas the two others (63/64 and 65/66) like the original
      monoclonal mouse antibody (K22) were predicted to stain both variants.
      Immunohistochemical staining procedures were subsequently performed on paraffin
      embedded human cerebral cortex and microarray slides containing 30 different
      human tissues. Western blotting confirmed the predicted specificity of the
      developed antibodies. K22, 63/64 and 65/66 displayed a similar neuronal staining
      pattern characterized by a distinct but weak nuclear staining, while the
      surrounding cytoplasm and proximal dendrites were more intensely stained.
      Interestingly, staining with 67 generated in contrast primarily an intense
      nuclear staining. The new antibodies resulted, furthermore, in a prominent
      neuroglial reaction characterized by staining of cell bodies, nuclei and glial
      processes. The tissue microarray analysis revealed that BRD1 was widely
      distributed in human tissues. The particular expression profile, e.g., the degree
      of nuclear and/or cytoplasmatic staining, seemed, however, to be highly tissue
      dependent. These results suggest a general role of BRD1 in the cell and stress
      that the two BRD1 variants may play different roles in the etiology of
      psychiatric disease.

PMID- 19763616
TI  - A novel 1p31.3p32.2 deletion involving the NFIA gene detected by array CGH in a
      patient with macrocephaly and hypoplasia of the corpus callosum.
AB  - Interstitial deletions or apparently balanced translocations involving bands 1p31
      and 1p32 in the short arm of chromosome 1 are rarely described chromosomal
      imbalances. To our knowledge, there have been six cases documented to date. Five
      of these cases, where the NFIA gene is involved, show complex central nervous
      system malformations and in some cases urinary tract defects. We report another
      case of a microdeletion with involvement of the NFIA gene in the short arm of
      chromosome 1 (del(1)(p31.3p32.2)) with, amongst other features, hypoplasia of the
      corpus callosum, ventriculomegaly, and dysmorphic features. A microdeletion
      1p31.3p32.2 which includes the NFIA gene is associated with hypoplasia of the
      corpus callosum, ventriculomegaly, and dysmorphic features.

PMID- 19763617
TI  - Involvement of tryptophan hydroxylase 2 (TPH2) gene polymorphisms in
      susceptibility to coronary artery lesions in Korean children with Kawasaki
      disease.
AB  - Kawasaki disease (KD) is an acute vasculitis of childhood that predominantly
      affects the coronary arteries. We investigated single nucleotide polymorphisms
      (SNPs) of the tryptophan hydroxylase 2 (TPH2) gene as risk factors for KD with
      coronary artery lesions (CALs) in Korean children. We genotyped two SNPs
      [rs7305115 (exon 7) and rs4290270 (exon 9)] using direct sequencing in 101 KD and
      256 control subjects. To analyze the genetic data, SNPStats, SNPAnalyzer, and
      Helixtree programs were used. The genotype analysis of rs7305115 and rs4290270
      showed no significant differences between KD and control groups. However, we
      found a statistically significant association between the two SNPs and the
      development of CALs in KD (p < 0.05). The minor homozygous genotype (rs7305115,
      AA genotype and rs42901270, AA genotype) of each SNP showed increased
      susceptibility to risk of CALs in KD patients. These results suggest that TPH2
      may be associated with the development of KD with CALs in Korean children.

PMID- 19763618
TI  - Non-accidental chlorpyrifos poisoning-an unusual cause of profound
      unconsciousness.
AB  - Chlorpyrifos is an organophosphorus anticholinesterase insecticide, and
      organophosphate intoxication can induce symptoms such as miosis, urination,
      diarrhea, diaphoresis, lacrimation, excitation of central nervous system,
      salivation, and consciousness disturbance (MUDDLES). Although accidental
      poisoning of children with drugs and chemicals is a common cause for
      consciousness disturbance in children, the possibility of deliberate poisoning is
      rarely considered. We report on a healthy 5-year 6-month-old boy with recurrent
      organophosphate intoxication. Reports of chlorpyrifos intoxication in children
      are quite rare. This case report demonstrates decision-making process and how to
      disclose deliberate chlorpyrifos poisoning of the toddler by the stepmother,
      another example of Munchausen syndrome by proxy.

PMID- 19763619
TI  - Clinical practice:   an approach to stridor in infants and children.
AB  - Stridor is the sound caused by abnormal air passage during breathing. The cause
      of stridor can be located anywhere in extrathoracic airway (nose, pharynx,
      larynx, and trachea) or the intrathoracic airway (tracheobronchial tree). Stridor
      may be acute (caused by inflammation/infection or foreign body inhalation) or
      chronic. It may be congenital or acquired. Stridor is a sign from which the
      underlying cause must be sought; it is not a diagnosis. The role of the
      pediatrician faced with a child or infant with noisy breathing is: (1) to
      determine the severity or respiratory compromise and the need for immediate
      intervention (to prevent respiratory failure); (2) to decide based upon history
      and clinical examination whether a significant lesion is suspected and, in the
      latter situation, to refer the child to an ENT surgeon for an upper and lower
      airway endoscopy; (3) to understand the consequences and management strategies of
      the underlying lesion and to collaborate with colleagues from related disciplines
      for follow-up and subsequent management of the child.

PMID- 19763620
TI  - Transglutaminase 2 as a cisplatin resistance marker in non-small cell lung
      cancer.
AB  - PURPOSE: Recently, it was reported that expression of transglutaminase 2 plays an
      important role in doxorubicin/cisplatin resistance in breast and ovarian cancer.
      The aims of this study were to verify the role of transglutaminase 2 in cisplatin
      response in non-small cell lung cancer (NSCLC) and to study if transglutaminase 2
      gene (TGM2) methylation can be a molecular marker for good response to cisplatin.
      METHODS: TGM2 promoter methylation was analyzed by sodium bisulfite sequencing.
      Cisplatin sensitivity was analyzed by treatment of cisplatin in NSCLC cell lines
      with/without TGM2 or TGM2 siRNA transfection. RESULTS: In one-third of NSCLC cell
      lines, TGase 2 gene (TGM2) was silenced by promoter methylation. The TGM2
      promoter-methylated cell lines (HCC-95 and HCC-1588) showed relatively higher
      sensitivity to cisplatin than the TGM2-expressing cell lines (NCI-H1299 and HCC
      1195). Down-regulation and over-expression of TGM2 in those NSCLC cells also
      suggested a positive correlation of cisplatin sensitivity and TGM2 inhibition.
      With doxorubicin, the relationship was quite similar. CONCLUSIONS: We showed that
      good responders of cisplatin in NSCLC could be identified by the promoter
      methylation of TGM2 and that TGase 2 inhibition appears to be an effective
      cisplatin-sensitizing modality in NSCLC.

PMID- 19763621
TI  - Current status and developments in diagnosis and therapy of multiple myeloma.

PMID- 19763622
TI  - Sex-specific antennal sensory system in the ant Camponotus japonicus: structure
      and distribution of sensilla on the flagellum.
AB  - The antennae are a critically important component of the ant's highly elaborated
      chemical communication systems. However, our understanding of the organization of
      the sensory systems on the antennae of ants, from peripheral receptors to central
      and output systems, is poorly understood. Consequently, we have used scanning
      electron and confocal laser microscopy to create virtually complete maps of the
      structure, numbers of sensory neurons, and distribution patterns of all types of
      external sensilla on the antennal flagellum of all types of colony members of the
      carpenter ant Camponotus japonicus. Based on the outer cuticular structures, the
      sensilla have been classified into seven types: coelocapitular, coeloconic,
      ampullaceal, basiconic, trichoid-I, trichoid-II, and chaetic sensilla. Retrograde
      staining of antennal nerves has enabled us to count the number of sensory neurons
      housed in the different types of sensilla: three in a coelocapitular sensillum,
      three in a coeloconic sensillum, one in an ampullaceal sensillum, over 130 in a
      basiconic sensillum, 50-60 in a trichoid-I sensillum, and 8-9 in a trichoid-II
      sensillum. The basiconic sensilla, which are cuticular hydrocarbon-receptive in
      the ant, are present in workers and unmated queens but absent in males.
      Coelocapitular sensilla (putatively hygro- and thermoreceptive) have been newly
      identified in this study. Coelocapitular, coeloconic, and ampullaceal sensilla
      form clusters and show biased distributions on flagellar segments of antennae in
      all colony members. The total numbers of sensilla per flagellum are about 9000 in
      unmated queens, 7500 in workers, and 6000 in males. This is the first report
      presenting comprehensive sensillar maps of antennae in ants.

PMID- 19763623
TI  - Discrete localization of various fatty-acid-binding proteins in various cell
      populations of mouse retina.
AB  - Various fatty acids (FAs) are involved as an energy source in many different
      functions in the organism. They are also essential ingredients of membranous
      lipids and act as intracellular signaling molecules. Intracellular fatty-acid
      binding proteins (FABPs) comprise a family of soluble lipid-binding proteins with
      low molecular masses and solubilize long-chain FAs to allow intracellular
      translocation in the aqueous cytosol. To clarify the functions of FABPs in the
      retina, which is remarkably rich in polyunsaturated FAs, we have investigated the
      localization of B (brain type)-, H (heart type)-, E (epidermal type)-, and A
      (adipocyte type)-FABPs in adult mouse retinae by immunohistochemistry. In order
      to determine the possible involvement of FABPs in retinal degenerative diseases,
      we have also examined changes in FABP expression in light-induced photoreceptor
      cell degeneration (photic injury). The discrete localization of B-, H-, E-, and A
      FABP species in various cell populations of the retina has been clarified: B-FABP
      is mainly localized in the cone photoreceptor cells, H-FABP in some populations
      of amacrine/bipolar/horizontal interneurons, and E-FABP in ganglion cells, with A
      FABP-like immunoreactivity being located in resident microglia of normal retinae.
      E-FABP has further been localized in invasive macrophages in damaged retinae
      following photic injury, allowing discrete identification of the resident
      microglia and invasive macrophages by A- and E-FABP immunoreactivity,
      respectively.

PMID- 19763624
TI  - Anatomical and histological profiling of orphan G-protein-coupled receptor
      expression in gastrointestinal tract of C57BL/6J mice.
AB  - G-protein-coupled receptors (GPCRs) constitute the largest family of
      transmembrane receptors and regulate a variety of physiological and disease
      processes. Although the roles of many non-odorant GPCRs have been identified in
      vivo, several GPCRs remain orphans (oGPCRs). The gastrointestinal (GI) tract is
      the largest endocrine organ and is a promising target for drug discovery. Given
      their close link to physiological function, the anatomical and histological
      expression profiles of benchmark GI-related GPCRs, such as the cholecystokinin-1
      receptor and GPR120, and 106 oGPCRs were investigated in the mucosal and muscle
      myenteric nerve layers in the GI tract of C57BL/6J mice by quantitative real-time
      polymerase chain reaction. The mRNA expression patterns of these benchmark
      molecules were consistent with previous in situ hybridization and
      immunohistochemical studies, validating the experimental protocols in this study.
      Of 96 oGPCRs with significant mRNA expression in the GI tract, several oGPCRs
      showed unique expression patterns. GPR85, GPR37, GPR37L1, brain-specific
      angiogenesis inhibitor (BAI) 1, BAI2, BAI3, and GPRC5B mRNAs were preferentially
      expressed in the muscle-myenteric nerve layer, similar to GPCRs that are
      expressed in both the central and enteric nerve systems and that play multiple
      regulatory roles throughout the gut-brain axis. In contrast, GPR112, trace amine
      associated receptor (TAAR) 1, TAAR2, and GPRC5A mRNAs were preferentially
      expressed in the mucosal layer, suggesting their potential roles in the
      regulation of secretion, immunity, and epithelial homeostasis. These anatomical
      and histological mRNA expression profiles of oGPCRs provide useful clues about
      the physiological roles of oGPCRs in the GI tract.

PMID- 19763625
TI  - Thymic stromal lymphopoietin enhances tight-junction barrier function of human
      nasal epithelial cells.
AB  - Epithelial-derived thymic stromal lymphopoietin (TSLP) triggers dendritic cell
      (DC)-mediated Th2-type inflammatory responses and is a master switch for allergic
      inflammatory diseases. In the present study, the expression and induction of TSLP
      and the effects of TSLP on the tight-junctional barrier of human nasal epithelial
      cells (HNECs) have been investigated in order to elucidate the role of TSLP in
      allergic rhinitis. We have found high expression of TSLP in the epithelium from
      patients with allergic rhinitis with recruitment and infiltration of DCs. In
      vitro, TSLP is significantly produced in HNECs after treatment with a toll-like
      receptor 2 (TLR2) ligand, Pam(3)Cys-Ser-(Lys)(4), and a mixture of interleukin
      1beta and tumor necrosis factor-alpha. Treatment with TSLP rapidly enhances the
      barrier function of cultured HNECs, together with an increase of tight-junction
      proteins claudin-1, -4, -7, and occludin. The nasal-epithelial-derived TSLP thus
      not only activates DCs but also preserves the epithelial barrier via the
      upregulation of tight-junction proteins, thereby regulating antigen sensitization
      during the early stage of allergic rhinitis.

PMID- 19763626
TI  - Dexamethasone effects on Na(v)1.6 in tooth pulp, dental nerves, and alveolar
      osteoclasts of adult rats.
AB  - Dexamethasone causes extensive physiologic reactions including the reduction of
      inflammation and pain. Here, we asked whether it also affected dental or
      periodontal cells or dental innervation by altering voltage-gated sodium channel
      Na(v)1.6 immunoreactivity (IR) or neural synaptophysin. Daily dexamethasone (0.2
      mg/kg) given for 1 week to rats caused 12-fold increased intensity of Na(v)1.6-IR
      in dendritic pulpal cells of normal molars and incisors compared with vehicle
      treatment. These cells also co-localized monocyte (ED-1) or dendritic cell
      (CD11b/Ox42) markers, and their location in molars expanded during dexamethasone
      treatment to include deeper pulp. Furthermore, dexamethasone caused a 10-fold
      decrease in the number of Na(v)1.6-immunoreactive multinucleate osteoclasts along
      the alveolar bone of molar root sockets. No changes occurred for neural Na(v)1.6
      at axonal nodes of Ranvier, even though IR for calcitonin gene-related peptide
      was greatly decreased, as expected, and neural synaptophysin-IR was decreased 59%
      by dexamethasone. At 4 days after tooth injury, pulpal vasodilation and increased
      Na(v)1.6-immunoreactive pulp cells were similar for all groups. Thus,
      dexamethasone changes dental pulp cell and alveolar osteoclast Na(v)1.6-IR in
      normal teeth, but different mechanisms occur after tooth injury when tissue
      reactions were similar for dexamethasone- and vehicle-treated rats. Steroid
      induced alterations of dental pain and inflammation coincide with altered
      exocytic capability in dental nerve fibers as shown by synaptophysin-IR and with
      altered pulp cell Na(v)1.6-IR and osteoclast number, but not with any changes in
      Na(v)1.6-IR for nodes of Ranvier in myelinated dental axons.

PMID- 19763627
TI  - Reduced dispersal propensity in the wingless waterstrider Aquarius najas in a
      highly fragmented landscape.
AB  - Dispersal behaviour of animals in fragmented habitats has generated intensive
      theoretical attention but empirical data on the evolution of dispersal are still
      relatively scarce. Theory predicts reduced dispersal propensity in small and
      isolated habitat patches. We tested these predictions in the waterstrider
      Aquarius najas, a wingless species with special habitat demands. Flightlessness
      constrains insect dispersal and as a stream specialist A. najas cannot survive on
      still water. Lakes therefore represent a dispersal barrier for this species. We
      measured dispersal propensity of the waterstrider A. najas which originated from
      ten fragmented populations. In the experiment, we transplanted laboratory-grown
      individuals to the field. We did not find differences between sex in dispersal
      propensity. However, we found that waterstriders that originated from small and
      isolated patches moved less than individuals from large and more continuous
      habitats. This suggests that the cost of dispersal over hostile surrounding
      habitats may be high. We conclude that a low likelihood of dispersal in A. najas
      is an adaptation to small and isolated stream habitats.

PMID- 19763628
TI  - Carbon allocation to defense, storage, and growth in seedlings of two temperate
      broad-leaved tree species.
AB  - Optimal carbon allocation to growth, defense, or storage is a critical trait in
      determining the shade tolerance of tree species. Thus, examining interspecific
      differences in carbon allocation patterns is useful when evaluating niche
      partitioning in forest communities. We hypothesized that shade-tolerant species
      allocate more carbon to defense and storage and less to growth compared to shade
      intolerant species. In gaps and forest understory, we measured relative growth
      rates (RGR), carbon-based defensive compounds (condensed tannin, total
      phenolics), and storage compounds (total non-structural carbohydrate; TNC) in
      seedlings of two tree species differing in shade tolerance. RGR was greater in
      the shade-intolerant species, Castanea crenata, than in the shade-tolerant
      species, Quercus mongolica var. grosseserrata, in gaps, but did not differ
      between the species in the forest understory. In contrast, concentrations of
      condensed tannin and total phenolics were greater in Quercus than in Castanea at
      both sites. TNC pool sizes did not differ between the species. Condensed tannin
      concentrations increased with increasing growth rate of structural biomass
      (GRstr) in Quercus but not in Castanea. TNC pool sizes increased with increasing
      GRstr in both species, but the rate of increase did not differ between the
      species. Accordingly, the amount of condensed tannin against TNC pool sizes was
      usually higher in Quercus than in Castanea. Hence, Quercus preferentially
      invested more carbon in defense than in storage. Such a large allocation of
      carbon to defense would be advantageous for a shade-tolerant species, allowing
      Quercus to persist in the forest understory where damage from herbivores and
      pathogens is costly. In contrast, the shade-intolerant Castanea preferentially
      invested more carbon in growth rather than defense (and similar amounts in
      storage as Quercus), ensuring establishment success in gaps, where severe
      competition occurs for light among neighboring plants. These contrasting carbon
      allocation patterns are closely associated with strategies for persistence in
      these species' respective habitats.

PMID- 19763629
TI  - Effects of bone and mineral metabolism on arterial elasticity  in chronic renal
      failure.
AB  - Arterial stiffness (Ast) individually predicts cardiovascular (CV) mortality. Ast
      increases via vascular calcification and can be characterized by pulse wave
      velocity (PWV). We assessed the influence of mineral and bone metabolism on Ast
      in dialyzed (D) and renal transplanted (Tx) children by measuring fetuin-A and
      bone markers [bone-specific alkaline phosphatase (BALP); beta-CrossLaps (beta)].
      Normalized PWV/height (PWV/h) of 11 D and 17 Tx patients was measured by
      applanation tonometry. Levels of calcium (Ca), phosphate (P), fetuin-A, and bone
      markers were analyzed. Ca x P/fetuin-A ratio was calculated to characterize the
      balance of calcification and inhibition. Cumulative dose of calcitriol was also
      assessed. Fetuin-A was lower in D and Tx compared with healthy controls. Bone
      markers and Ca x P/ fetuin-A of D were significantly higher than those of Tx and
      controls. In D PWV/h correlated with Ca x P/fetuin-A and BALP (r=0.8; p=0.005,
      r=0.6, p=0.05, respectively); BALP correlated with Ca x P/fetuin-A (r=0.7,
      p=0.01). In Tx, there was a correlation between calcitriol administered before
      transplantation and PWV/h (r=0.5, p=0.04). Increased bone turnover was coupled
      with an increased potential of calcium-phosphate precipitation, as shown by the
      increased Ca x P/fetuin-A. It might explain the connection between disturbed
      mineral and bone metabolism and Ast. Tx might be beneficial on Ast, though follow
      up studies are needed.

PMID- 19763631
TI  - [Pain and quality of life for living donors after nephrectomy].
AB  - BACKGROUND: This survey focussed on chronic postoperative pain and impairment of
      quality of life after living donor nephrectomy. METHODS: Out of a total of 82
      donors 58 (71%) were examined using the Chronic Pain Grade (CPG) by von Korff and
      Short-Form 12 (SF-12). RESULTS: Of the donors 34% suffered from chronic
      postoperative pain 22 months (range 9-57 months) after nephrectomy and in 55% of
      these cases the pain interfered with daily life activities. The quality of life
      was almost comparable with those of the average German population, but was
      reduced by chronic postoperative pain particularly with respect to the mental
      state. CONCLUSION: Measures have to be taken to prevent chronic postoperative
      pain and donors should be encouraged to express their pain to ensure an adequate
      pain therapy.

PMID- 19763632
TI  - The effects of gap size on some microclimate variables during late summer and
      autumn in a temperate broadleaved deciduous forest.
AB  - The creation of gaps can strongly influence forest regeneration and habitat
      diversity within forest ecosystems. However, the precise characteristics of such
      effects depend, to a large extent, upon the way in which gaps modify microclimate
      and soil water content. Hence, the aim of this study was to understand the
      effects of gap creation and variations in gap size on forest microclimate and
      soil water content. The study site, in North West England, was a mixed temperate
      broadleaved deciduous forest dominated by mature sessile oak (Quercus petraea),
      beech (Fagus sylvatica) and ash (Fraxinus excelsior) with some representatives of
      sycamore (Acer pseudoplatanus). Solar radiation (I), air temperature (T(A)), soil
      temperature (T(S)), relative humidity (h), wind speed (v) and soil water content
      (Psi) were measured at four natural treefall gaps created after a severe storm in
      2006 and adjacent sub-canopy sites. I, T(A), T(S), and Psi increased
      significantly with gap size; h was consistently lower in gaps than the sub-canopy
      but did not vary with gap size, while the variability of v could not be explained
      by the presence or size of gaps. There were systematic diurnal patterns in all
      microclimate variables in response to gaps, but no such patterns existed for Psi.
      These results further our understanding of the abiotic and consequent biotic
      responses to gaps in broadleaved deciduous forests created by natural treefalls,
      and provide a useful basis for evaluating the implications of forest management
      practices.

PMID- 19763633
TI  - Differential palliative care issues in patients with primary and secondary brain
      tumours.
AB  - INTRODUCTION: Cancer may affect the central nervous system either by primary or
      secondary brain tumours (PBT/SBT). Specific needs of these patients and special
      requirements of services caring for them have not been adequately addressed so
      far. METHODS: Since 1999, an annual, 3-month census is being conducted in
      different palliative care settings throughout Germany. Pooled data from the years
      2002-2005 were analysed to test for differences between patients with PBT, SBT
      and other palliative care patients (OP). Symptom frequencies, ECOG status and
      nursing needs were tested for differences (chi(2)). Free text entries for reasons
      for admission were recorded, categorised and analysed descriptively. RESULTS: A
      total of 5,684 patients were documented (PBT n = 153, 2.7%; SBT n = 661, 11.9%;
      OP n = 4,872, 85.4%). For patients with PBT, poor functional status and high need
      for nursing support was reported more frequently than for patients with SBT and
      OP. For patients with PBT/SBT physical symptoms (pain, nausea, vomiting,
      constipation and loss of appetite) were documented less frequently and in lower
      intensity than for OP. However, nursing, psychological, and social
      problems/symptoms were documented significantly more often and showed higher
      intensity, particularly the patients'' need for support with the activities of
      daily living, disorientation/confusion of the patients and overburdening of the
      family. For 67% of all patients, a reason for admission was documented in free
      text. Main reasons were symptom control (OP>SBT>PBT), social issues (PBT>SBT>OP),
      functional deficits (PBT>SBT>OP) and cognitive impairment (PBT/SBT>OP). Distinct
      neurological deficits and problems were documented more often as secondary ICD
      diagnoses than as a leading reason for admission. CONCLUSION: The specific
      palliative care problems and the rationales leading to health care utilisation
      point to the need for an appropriate interdisciplinary and multi-professional
      provision of care for patients with brain malignancies, with a particular view on
      the needs of the families and an early integration of social and psychological
      support.

PMID- 19763634
TI  - Clinical and radiological evaluation of Trabecular Metal and the Smith-Robinson
      technique in anterior cervical fusion for degenerative disease: a prospective,
      randomized, controlled study with 2-year follow-up.
AB  - A prospective, randomized, controlled study was carried out to compare the
      radiological and clinical outcomes after anterior cervical decompression and
      fusion (ACDF) with Trabecular Metal (TM) to the traditional Smith-Robinson (SR)
      procedure with autograft. The clinical results of cervical fusion with autograft
      from the iliac crest are typically satisfactory, but implications from the donor
      site are frequently reported. Alternative materials for cervical body interfusion
      have shown lower fusion rates. Trabecular Metal is a porous tantalum biomaterial
      with structure and mechanical properties similar to that of trabecular bone and
      with proven osteoconductivity. As much as 80 consecutive patients planned for
      ACDF were randomized for fusion with either TM or tricortical autograft from the
      iliac crest (SR) after discectomy and decompression. Digitized plain radiographic
      images of 78 (98%) patients were obtained preoperatively and at 2-year follow-up
      and were subsequently evaluated by two senior radiologists. Fusion/non-fusion was
      classified by visual evaluation of the A-P and lateral views in forced
      flexion/extension of the cervical spine and by measuring the mobility between the
      fused vertebrae. MRI of 20 TM cases at 2 years was successfully used to assess
      the decompression of the neural structures, but was not helpful in determining
      fusion/non-fusion. Pain intensity in the neck, arms and pelvis/hip were rated by
      patients on a visual analog scale (VAS) and neck function was rated using the
      Neck Disability Index (NDI) the day before surgery and 4, 12 and 24 months
      postoperatively. Follow-ups at 12 and 24 months were performed by an unbiased
      observer, when patients also assessed their global outcome. Fusion rate in the SR
      group was 92%, and in the TM group 69% (P < 0.05). The accuracy of the
      measurements was calculated to be 2.4 degrees . Operating time was shorter for
      fusion with TM compared with autograft; mean times were 100 min (SD 18) and 123
      min (SD 23), respectively (P = 0.001). The patients' global assessments of their
      neck and arm symptoms 2 years postoperatively for the TM group were rated as 79%
      much better or better after fusion with TM and 75% using autograft. Pain scores
      and NDI scores were significantly improved in both groups when compared with
      baseline at all follow-ups, except for neck pain at 1 year for the TM group.
      There was no statistically significant difference in clinical outcomes between
      fusion techniques or between patients who appeared radiologically fused or non
      fused. There was no difference in pelvic/hip pain between patients operated on
      with or without autograft. In our study, Trabecular Metal showed a lower fusion
      rate than the Smith-Robinson technique with autograft after single-level anterior
      cervical fusion without plating. There was no difference in clinical outcomes
      between the groups. The operative time was shorter with Trabecular Metal
      implants.

PMID- 19763635
TI  - Radiological analysis of ankylosing spondylitis patients with severe kyphosis
      before and after pedicle subtraction osteotomy.
AB  - This is a radiographic study of ankylosing spondylitis patients with severe fixed
      kyphotic deformity who underwent pedicle subtraction osteotomy. Our goal was to
      measure and validate new angle to assess global kyphosis and to evaluate the
      radiological outcomes after surgery. This is the first report which describes new
      angle to assess global kyphosis (T1-S1). Pre and postoperative controls were
      compared according to the Pelvic Incidence. The sagittal parameters ankylosing
      spondylitis patients were compared with 154 asymptomatic patients. In addition to
      the pelvic parameters and the C7 tilt, we used the spino-sacral angle. Pelvic
      incidence in ankylosing spondylitis patients was higher than asymptomatic
      population (61 vs. 51 degrees). For a same tilt of C7 for both groups, the low
      pelvic incidence group had a lower sacral slope and pelvic tilt and a higher
      global kyphosis (spino-sacral angle = 90 degrees) than the high pelvic incidence
      group (spino-sacral angle = 98 degrees ). In the adult volunteers, the C7 tilt
      and spino-sacral angle measured, respectively, 95 and 135 degrees. The
      preoperative C7 tilt measured 73 degrees and increased to 83 degrees (p =
      0.0025). The preoperative spino-sacral angle measured 96 degrees and increased to
      113.3 degrees (p = 0.003). A low pelvic incidence pelvis has a lower sacral slope
      than in high pelvic incidence and can support a bigger kyphosis. All the
      parameters were improved by the pedicle subtraction osteotomy, but the average
      spino-sacral angle remained lower than the control group. When C7 tilt was useful
      to assess the improvement of the balance, SSA allowed a better evaluation of the
      correction of kyphosis itself.

PMID- 19763636
TI  - Safety of thoracic pedicle screw application using the funnel technique in
      Asians: a cadaveric evaluation.
AB  - The objective of this cadaveric study is to determine the safety and outcome of
      thoracic pedicle screw placement in Asians using the funnel technique. Pedicle
      screws have superior biomechanical as well as clinical data when compared to
      other methods of instrumentation. However, misplacement in the thoracic spine can
      result in major neurological implications. There is great variability of the
      thoracic pedicle morphometry between the Western and the Asian population. The
      feasibility of thoracic pedicle screw insertion in Asians has not been fully
      elucidated yet. A pre-insertion radiograph was performed and surgeons were
      blinded to the morphometry of the thoracic pedicles. 240 pedicle screws were
      inserted in ten Asian cadavers from T1 to T12 using the funnel technique. 5.0 mm
      screws were used from T1 to T6 while 6.0 mm screws were used from T7 to T12.
      Perforations were detected by direct visualization via a wide laminectomy. The
      narrowest pedicles are found between T3 and T6. T5 pedicle width is smallest
      measuring 4.1 +/- 1.3 mm. There were 24 (10.0%) Grade 1 perforations and only 1
      (0.4%) Grade 2 perforation. Grade 2 or worse perforation is considered
      significant perforation which would threaten the neural structures. There were
      twice as many lateral and inferior perforations compared to medial perforations.
      48.0% of the perforations occurred at T1, T2 and T3 pedicles. Pedicle fracture
      occurred in 10.4% of pedicles. Intra-operatively, the absence of funnel was found
      in 24.5% of pedicles. In conclusion, thoracic pedicle screws using 5.0 mm at T1
      T6 and 6.0 mm at T7-T12 can be inserted safely in Asian cadavers using the funnel
      technique despite having smaller thoracic pedicle morphometry.

PMID- 19763637
TI  - Spinal cord compression caused by idiopathic intradural arachnoid cysts of the
      spine: review of the literature and illustrated case.
AB  - Intradural spinal arachnoid cysts with cord compression are rare. When becoming
      symptomatic they cause variable symptoms involving gait disturbance, paraparesis
      or tetraparesis and neuropathic pain, decreasing significantly the patients' life
      quality. The extension of such cysts averages 3.7 vertebral bodies. The diagnosis
      is clinical and radiological with the use of MRI, CT myelography or a combination
      of both. The best treatment option is complete removal of the cyst. However, even
      when paresis is regressing there is no good recovery from neuropathic pain.
      Laminectomy approach can cause postoperative complications especially when the
      cyst(s) expand(s) in more than one level. Alternatively, a cyst fenestration can
      be performed, including the levels of the maximal spinal cord compression. The
      clinical outcome is as good as after the cyst resection enabling the patient to
      walk again. The neuropathic pain may persist and require medication. A clinical
      case is presented, and the literature is reviewed. In the present case we report
      a patient with intradural arachnoid cysts extending from T6 to L2 and causing
      severe gait ataxia as well as neuropathic pain and hypaesthesia. The spinal-cord
      was compressed at T8 and T12. Surgical treatment with partial cyst resection in
      the compressed levels with an interlaminar approach brought similar results as
      complete resection. The patient was able to walk without help which was not
      possible before surgery. The cysts' extension is impressive as well as the
      minimal operative procedure.

PMID- 19763638
TI  - The effect of different design concepts in lumbar total disc  arthroplasty on the
      range of motion, facet joint forces and  instantaneous center of rotation of a L4
      5 segment.
AB  - Although both unconstrained and constrained core lumbar artificial disc designs
      are in clinical use, the effect of their design on the range of motion, center of
      rotations, and facet joint forces is not well understood. It is assumed that the
      constrained configuration causes a fixed center of rotation with high facet
      forces, while the unconstrained configuration leads to a moving center of
      rotation with lower loaded facets. The authors disagree with both assumptions and
      hypothesized that the two different designs do not lead to substantial
      differences in the results. For the different implant designs, a three
      dimensional finite element model was created and subsequently inserted into a
      validated model of a L4-5 lumbar spinal segment. The unconstrained design was
      represented by two implants, the Charite disc and a newly developed disc
      prosthesis: Slide-Disc. The constrained design was obtained by a modification of
      the Slide-Disc whereby the inner core was rigidly connected to the lower metallic
      endplate. The models were exposed to an axial compression preload of 1,000 N.
      Pure unconstrained moments of 7.5 Nm were subsequently applied to the three
      anatomical main planes. Except for extension, the models predicted only small and
      moderate inter-implant differences. The calculated values were close to those of
      the intact segment. For extension, a large difference of about 45% was calculated
      between both Slide-Disc designs and the Charite disc. The models predicted higher
      facet forces for the implants with an unconstrained core compared to an implant
      with a constrained core. All implants caused a moving center of rotation. Except
      for axial rotation, the unconstrained and constrained configurations mimicked the
      intact situation. In axial rotation, only the Slide- Disc with mobile core
      reproduced the intact behavior. Results partially support our hypothesis and
      imply that different implant designs do not lead to strong differences in the
      range of motion and the location of center of rotations. In contrast, facet
      forces appeared to be strongly dependent on the implant design. However, due to
      the great variability in facet forces reported in the literature, together with
      our results, we could speculate that these forces may be more dependent on the
      individual spine geometry rather than a specific implant design.

PMID- 19763639
TI  - Surgical treatment of post-traumatic kyphosis in the thoracolumbar spine:
      indications and technical aspects.
AB  - Indications for correction of post-traumatic kyphotic deformity of the spine and
      technical aspects of the surgical procedure are reviewed. Surgical correction of
      post-traumatic deformity of the spine should be considered in patients presenting
      a local excess of kyphosis in the fractured area superior to 20 degrees with poor
      functional tolerance. Severe pain, explained by objective factors such as canal
      or neuroforamen compromise with or without peripheral symptoms, angular
      deformity, non-union, focal instability, adjacent painful compensatory deformity
      such as lumbar hyper-lordosis or thoracic hypo-kyphosis or lordosis is a further
      argument for surgery. More advanced age, litigation, work-related trauma are
      negative factors. Planning of the surgical procedure includes the choice of the
      approach(es), the corrective means: subtraction osteotomy or vertebral body
      reconstruction and the nature and extent of osteosynthesis and fusion. Decision
      making factors includes: level of trauma, severity of deformity, history of
      previous surgery in the area of deformity, bone quality, age of fracture.
      Corrective surgery of a post-traumatic deformity of the spine is a difficult
      procedure that should be considered only by an experienced team, after careful
      consideration of the indication and with the consent of a well-informed patient.
      Complications do occur and lead to the need of re-intervention in up to 10% of
      our cases. However, significant complications with lasting consequences did not
      occur in our experience. The more severe is the deformity, the better are the
      chances to improve the patient, as long as the surgical goals are fulfilled.

PMID- 19763640
TI  - Image-guided spine surgery: state of the art and future directions.
AB  - Navigation technology is a widely available tool in spine surgery and has become
      a part of clinical routine in many centers. The issue of where and when
      navigation technology should be used is still an issue of debate. It is the aim
      of this study to give an overview on the current knowledge concerning the
      technical capabilities of image-guided approaches and to discuss possible future
      directions of research and implementation of this technique. Based on a Medline
      search total of 1,462 publications published until October 2008 were retrieved.
      The abstracts were scanned manually for relevance to the topics of navigated
      spine surgery in the cervical spine, the thoracic spine, the lumbar spine, as
      well as ventral spine surgery, radiation exposure, tumor surgery and cost
      effectivity in navigated spine surgery. Papers not contributing to these subjects
      were deleted resulting in 276 papers that were included in the analysis. Image
      guided approaches have been investigated and partially implemented into clinical
      routine in virtually any field of spine surgery. However, the data available is
      mostly limited to small clinical series, case reports or retrospective studies.
      Only two RCTs and one metaanalysis have been retrieved. Concerning the most
      popular application of image-guided approaches, pedicle screw insertion, the
      evidence of clinical benefit in the most critical areas, e.g. the thoracic spine,
      is still lacking. In many other areas of spine surgery, e.g. ventral spine
      surgery or tumor surgery, image-guided approaches are still in an experimental
      stage. The technical development of image-guided techniques has reached a high
      level as the accuracies that can be achieved technically meet the anatomical
      demands. However, there is evidence that the interaction between the surgeon
      ('human factor') and the navigation system is a source of inaccuracy. It is
      concluded that more effort needs to be spend to understand this interaction.

PMID- 19763642
TI  - Genetic relatedness and virulence gene profiles of Escherichia coli strains
      isolated from septicaemic and uroseptic patients.
AB  - We investigated the relationship between clonality and virulence factors (VFs) of
      a collection of Escherichia coli strains isolated from septicaemic and uroseptic
      patients with respect to their origin of translocation. Forty septicaemic and 30
      uroseptic strains of E. coli were tested for their phylogenetic groupings,
      genetic relatedness using randomly amplified polymorphic DNA (RAPD), biochemical
      fingerprinting method (biochemical phenotypes [BPTs]), adherence to HT-29 cells
      and the presence of 56 E. coli VF genes. Strains belonging to phylogenetic groups
      B2 and D constituted 93% of all strains. Fifty-four (77%) strains belonged to two
      major BPT/RAPD clusters (A and B), with cluster A carrying significantly (P =
      0.0099) more uroseptic strains. The degree of adhesion to HT-29 cells of
      uroseptic strains was significantly (P = 0.0012) greater than that of septicaemic
      strains. Of the 56 VF genes tested, pap genes was the only group that were found
      significantly (P < 0.0001) more often among uroseptic isolates. Phylogenetic
      group B2 contained a significantly higher number of strains carrying pap genes
      than those in group D. We conclude that uroseptic E. coli are clonally different
      from septicaemic strains, carry more pap genes and predominantly adhere more to
      the HT-29 cell model of the gut.

PMID- 19763643
TI  - Oral valganciclovir treatment in newborns with symptomatic congenital
      cytomegalovirus infection.
AB  - This study was performed to assess oral valganciclovir V-GCV (GCV pro-drug), 15
      mg/kg bid for 6 weeks to 13 neonates with symptomatic congenital cytomegalovirus
      (CMV). We monitored plasma levels of GCV within 30 days of therapy: C(trough),
      and C(2h) (before and the 2 hours after administration), we performed viral
      assessment in plasma and urine and tolerability at baseline, and every fortnight.
      Pharmacokinetics showed GCV stable and effective plasma concentrations: mean
      C(trough) = 0.51 +/- 0.3 and C(2h) : 3.81 +/- 1.37 microg/ml. No significant
      variability was seen neither intra-patient nor inter-patients. One newborn
      discontinued therapy because of thrombocytopenia, another finished with a
      neutrophils count of 1,000/microl. At the end of therapy 6 out of 12 and 8 out of
      12 newborns were negative for CMV in urine and plasma. The 4 newborns positive
      for CMV DNA showed a 90% reduction of pre-therapy values. Clinically, the 4
      patients reporting hepatic disease and the 3 with thrombocytopenia recovered
      after 6 weeks of therapy. Eight newborns suffered from SNHL; at the 6-month
      follow-up no patients had worsened, 2 had improved, and no deterioration was
      reported in 3 newborns with chorioretinitis scarring. The paucity of adverse
      events, and the effectiveness and stability of drug plasma concentrations are the
      important findings of our study.

PMID- 19763644
TI  - In vitro activities of moxifloxacin and tigecycline against bacterial isolates
      associated with intraabdominal infections at a medical center in Taiwan, 2001
      2006.
AB  - A total of 569 nonduplicate isolates recovered from patients with community-onset
      or hospital-onset intraabdominal infections (IAIs) from 2001 to 2006 were
      studied. These included 28 Staphylococcus aureus and 541 Gram-negative isolates
      (33.6% Escherichia coli, 29.0% Klebsiella pneumoniae, 8.1% Acinetobacter
      baumannii, and 6.3% Pseudomonas aeruginosa). Minimum inhibitory concentrations
      (MICs) of the isolates to moxifloxacin, imipenem, and ciprofloxacin were
      determined using the agar dilution method and to tigecycline using the broth
      microdilution method. Extended-spectrum beta-lactamase (ESBL) producers were
      found in 15.5% (29 out of 182) of E. coli, 15.3% (24 out of 157) of K.
      pneumoniae, and 15.4% (2 out of 13) of K. oxytoca isolates. More than 85% of
      Enterobacteriaceae were susceptible to moxifloxacin, but this percentage was
      lower among E. coli (78%). The percentage of E. coli (K. pneumoniae) isolates
      that were not susceptible to moxifloxacin was 6% (0%) in 2001, 39% (17%) in 2003,
      and 21% (14%) in 2006. Tigecycline exhibited good in vitro activities against all
      S. aureus and >95% of all Enterobacteriaceae tested. Among the 24 isolates of
      ESBL-producing K. pneumoniae, 4 had tigecycline MICs > or = 2 microg/ml. Eighty
      percent of A. baumannii isolates exhibited tigecycline MICs of < or = 2
      microg/ml. This study found that moxifloxacin and tigecycline exhibited good in
      vitro activity against bacterial isolates causing IAIs.

PMID- 19763645
TI  - Bioactive modification of silicon surface using self-assembled hydrophobins from
      Pleurotus ostreatus.
AB  - A crystalline silicon surface can be made biocompatible and chemically stable by
      a self-assembled biofilm of proteins, the hydrophobins (HFBs) purified from the
      fungus Pleurotus ostreatus. The protein-modified silicon surface shows an
      improvement in wettability and is suitable for immobilization of other proteins.
      Two different proteins were successfully immobilized on the HFBs-coated chips:
      the bovine serum albumin and an enzyme, a laccase, which retains its catalytic
      activity even when bound on the chip. Variable-angle spectroscopic ellipsometry
      (VASE), water contact angle (WCA), and fluorescence measurements demonstrated
      that the proposed approach in silicon surface bioactivation is a feasible
      strategy for the fabrication of a new class of hybrid devices.

PMID- 19763646
TI  - Commentary on "Adhesion and membrane tension of single vesicles and living cells
      using a micropipette-based technique" by M.-J. Colbert et al.

PMID- 19763647
TI  - Quantification of growth asymmetries in developing epithelia.
AB  - Many developmental processes of multicellular organisms involve the patterning
      and growth of two-dimensional tissues, so called epithelia. We have quantified
      the growth of the wing imaginal disk, which is the precursor of the adult wing,
      of the fruit fly Drosophila melanogaster. We find that growth follows a simple
      rule with exponentially decreasing area growth rate. Anisotropies of growth can
      be precisely determined by comparing experimental results to a continuum theory.
      Growth anisotropies are to good approximation constant in space and time. They
      are weak in wild-type wing disks but threefold increased in GFP-Dpp disks in
      which the morphogen Dpp is overexpressed. Our findings indicate that morphogens
      such as Dpp control tissue shape via oriented cell divisions that generate
      anisotropic growth.

PMID- 19763648
TI  - The 'I' and the 'Me' in self-referential awareness: a neurocognitive hypothesis.
AB  - The nature of the 'self' and self-referential awareness has been one of the most
      debated issues in philosophy, psychology and cognitive neuroscience.
      Understanding the neurocognitive bases of self-related representation and
      processing is also crucial to research on the neural correlates of consciousness.
      The distinction between an 'I', corresponding to a subjective sense of the self
      as a thinker and causal agent, and a 'Me', as the objective sense of the self
      with the unique and identifiable features constituting one's self-image or self
      concept, suggested by William James, has been re-elaborated by authors from
      different theoretical perspectives. In this article, empirical studies and
      theories about the 'I' and the 'Me' in cognition and self-related awareness are
      reviewed, including the relationships between self and perception, self and
      memory, the development of the self, self-referential stimulus processing, as
      well as related neuroimaging studies. Subsequently, the relations between self
      and different aspects of consciousness are considered. On the basis of the
      reviewed literature and with reference to Block's distinction between phenomenal
      and access consciousness, a neurocognitive hypothesis is formulated about 'I'
      related and 'Me'-related self-referential awareness. This hypothesis is extended
      to metacognitive awareness and a form of non-transitive consciousness,
      characteristic of meditation experiences and studies, with particular reference
      to the notion of mindfulness and other Buddhist constructs.

PMID- 19763650
TI  - Dimethyl sulphoxide dose-response on rat retinal function.
AB  - The aim of the study is to determine whether dimethyl sulphoxide (DMSO), a common
      laboratory solvent, impacts retinal function. Long Evans rats (n = 17) were
      intravitreally injected with five different doses of DMSO representative of those
      reported in the literature and spanning over 3 log units of vitreal concentration
      (0.01-8%). Retinal function was evaluated 1 h after injection using
      electroretinograms, and the waveform was decomposed into outer (photoreceptor),
      middle (ON-bipolar cell) and inner retinal (amacrine and ganglion cell)
      components. DMSO induces a dose-dependent decrease in retinal function for
      concentrations of 0.6% or more which is retinal layer specific. The
      photoreceptors of the outer retina returned normal responses at all doses (P >
      0.05), whereas the mid-retinal bipolar cell response showed dose-dependent losses
      ranging from 21 +/- 1 to 82 +/- 1% (0.6-8% DMSO; P < 0.05). In a similar dose
      dependent fashion, the inner retinal response was also affected by DMSO (0.6-8%:
      23 +/- 12 to 98 +/- 3% loss, P < 0.05). A single dose of DMSO < or =0.1% (2.96 x
      10(-5) microM) may be safely used to dilute compounds injected into the vitreous
      of a rat eye. Higher doses produce short-term (at least 24 h) retinal
      dysfunction.

PMID- 19763649
TI  - The significance of neuronal and glial cell changes in the rat retina during
      oxygen-induced retinopathy.
AB  - Retinopathy of prematurity is a devastating vascular disease of premature
      infants. A number of studies indicate that retinal function is affected in this
      disease. Using the rat model of oxygen-induced retinopathy, it is possible to
      explore more fully the complex relationship between neuronal, glial and vascular
      pathology in this condition. This review examines the structural and functional
      changes that occur in the rat retina following oxygen-induced retinopathy. We
      highlight that vascular pathology in rats is characterized by aberrant growth of
      blood vessels into the vitreous at the expense of blood vessel growth into the
      body of the retina. Moreover, amino acid neurochemistry, a tool for examining
      neuronal changes in a spatially complete manner reveals widespread changes in
      amacrine and bipolar cells. In addition, neurochemical anomalies within inner
      retinal neurons are highly correlated with the absence of retinal vessels. The
      key cell types that link blood flow with neuronal function are macroglia.
      Macroglia cells, which in the retina include astrocytes and Muller cells, are
      affected by oxygen-induced retinopathy. Astrocyte loss occurs in the peripheral
      retina, while Muller cells show signs of reactive gliosis that is highly
      localized to regions that are devoid of intraretinal blood vessels. Finally, we
      propose that treatments, such as blockade of the renin-angiotensin system, that
      not only targets pathological angiogenesis, but that also promotes re
      vascularization of the retina are likely to prove important in the treatment of
      those with retinopathy of prematurity.

PMID- 19763651
TI  - Orthoimplants: an alternative treatment for SAHS?
AB  - Numerous sleep studies have been published recently regarding the use of
      intraoral devices (ODs) for the treatment of sleep apnea-hypopnea syndrome
      (SAHS). The effectiveness of these devices varies, however, according to the
      series studied (patient characteristics, parameters assessed, type of device,
      etc.). Two factors should always be assessed: the presence of an appropriate
      dental support and a possible temporomandibular joint pathology which can, on
      occasions, contraindicate the use of these devices. OBJECTIVES: To use
      orthoimplants as orthodontic anchorages for intermaxillary elastic bands which
      allow a mandibular advancement to be performed as an alternative treatment to ODs
      in SAHS patients without appropriate dental support. MATERIALS AND METHODS: Four
      orthoimplants were placed in an edentulous SAHS patient who did not tolerate
      continuous positive airway pressure (CPAP). The mandible is pushed forward using
      orthodontic elastic bands anchored to the orthoimplants. RESULTS AND CONCLUSIONS:
      Although more studies are still required, orthoimplants could be an alternative
      treatment for reducing snoring and the apnea-hypopnea index and increasing SaO2,
      which should be considered for patients who do not tolerate CPAP and lack
      appropriate dental support for attaching intraoral devices.

PMID- 19763652
TI  - Improvement in quality of life after adenotonsillectomy in a child with Prader
      Willi syndrome.
AB  - INTRODUCTION: We report a child with Prader Willi syndrome who developed
      obstructive sleep apnea (OSA). This patient underwent surgical treatment for OSA.
      There was improvement not only on her OSA but in her quality of life score as
      well. This report highlights the need for a comprehensive assessment in the
      management of patients with Prader Willi syndrome.

PMID- 19763654
TI  - Kinetic study of the prooxidant effect of alpha-tocopherol. Hydrogen abstraction
      from lipids by alpha-tocopheroxyl radical.
AB  - A kinetic study of the prooxidant effect of alpha-tocopherol was performed. The
      rates of allylic hydrogen abstraction from various unsaturated fatty acid esters
      (ethyl stearate 1, ethyl oleate 2, ethyl linoleate 3, ethyl linolenate 4, and
      ethyl arachidonate 5) by alpha-tocopheroxyl radical in toluene were determined,
      using a double-mixing stopped-flow spectrophotometer. The second-order rate
      constants (k (p)) obtained are <1 x 10(-2) M(-1 )s(-1) for 1, 1.90 x 10(-2) M(-1
      )s(-1) for 2, 8.33 x 10(-2 )M(-1 )s(-1) for 3, 1.92 x 10(-1) M(-1 )s(-1) for 4,
      and 2.43 x 10(-1 )M(-1 )s(-1) for 5 at 25.0 degrees C. Fatty acid esters 3, 4,
      and 5 contain two, four, and six -CH(2)- hydrogen atoms activated by two pi
      electron systems (-C=C-CH(2)-C=C-). On the other hand, fatty acid ester 2 has
      four -CH(2)- hydrogen atoms activated by a single pi-electron system (-CH(2)-C=C
      CH(2)-). Thus, the rate constants, k (abstr)/H, given on an available hydrogen
      basis are k (p)/4 = 4.75 x 10(-3 )M(-1 )s(-1) for 2, k (p)/2 = 4.16 x 10(-2) M(-1
      )s(-1) for 3, k (p)/4 = 4.79 x 10(-2 )M(-1 )s(-1) for 4, and k (p)/6 = 4.05 x 10(
      2 )M(-1 )s(-1) for 5. The k (abstr)/H values obtained for 3, 4, and 5 are similar
      to each other, and are by about one order of magnitude higher than that for 2.
      From these results, it is suggested that the prooxidant effect of alpha
      tocopherol in edible oils, fats, and low-density lipoproteins may be induced by
      the above hydrogen abstraction reaction.

PMID- 19763655
TI  - Regulation of HMGCoA reductase activity by policosanol and octacosadienol, a new
      synthetic analogue of octacosanol.
AB  - Octacosa-10,19-dien-1-ol is a newly synthesized long-chain alcohol, an
      unsaturated analogue of 1-octacosanol, the major component of policosanol, the
      purified natural mixture of different higher aliphatic alcohols obtained from
      sugarcane wax. Our efficient synthetic protocol (five steps with 50% overall
      yield) is well suited for gram scale preparations and a rapid generation of
      analogues with different degrees of unsaturation. Beneficial effects of
      policosanol in the prevention of atherosclerosis and thromboembolic disorders
      have been reported and related to the inhibition of sterol biosynthesis possibly
      by the regulation of the activity of HMGCoA reductase mediated by AMP-dependent
      kinase AMPK. We have compared the effect of octacosadienol and policosanol on the
      regulation of HMGCoA reductase in HUVEC and HepG2 human hepatoma cells.
      Octacosadienol was as effective as policosanol in inhibiting the upregulation of
      HMGCoA reductase, in inducing the phosphorylation of AMPK and in downregulating
      the HMGCoA reductase mRNA.

PMID- 19763656
TI  - Simple methods to detect triacylglycerol biosynthesis in a yeast-based
      recombinant system.
AB  - Standard methods to quantify the activity of triacylglycerol (TAG) synthesizing
      enzymes DGAT and PDAT (TAG-SE) require a sensitive but rather arduous laboratory
      assay based on radio-labeled substrates. Here we describe two straightforward
      methods to detect TAG production in baker's yeast Saccharomyces cerevisiae. First
      we demonstrate that a quadruple knockout yeast strain deficient in storage lipids
      has a reduced growth rate in a medium supplemented with fatty acids. This
      phenotype is rescued by restoring TAG biosynthesis and can be thus used to select
      yeast cells expressing a recombinant TAG-SE. In the second method, the activity
      of the recombinant enzyme is measured in a fluorescent in situ assay using Nile
      red dye that is specific for neutral lipids. Correlation between Nile red
      fluorescence and enzyme activity is demonstrated with several mutants of a TAG
      synthesizing enzyme. This yeast live-cell-based assay is rapid, inexpensive,
      sensitive, and is amenable to high-throughput applications. The methods can be
      used for a variety of applications such as isolation of novel genes, directed
      evolution, gene-specific drug screening and will facilitate novel approaches in
      the research of TAG-SE.

PMID- 19763657
TI  - Personalised food: how personal is it?
AB  - Consumer goods became increasingly personalised, particularly during the last
      half of the 20th century. Foods and food products have been added a new flavour
      in this consumer trends with increasingly personalised values of convenience,
      cost, packaging, and taste. Now functional food industry is ready to take its
      next venture in a relatively new domain personalising health. Whether the goal of
      matching foods to individual genotypes to improve the health of those individuals
      can be attained, and personalised nutrigenomic foods enter the world's food
      markets, depends on numerous hurdles being overcome: some scientific in nature,
      some technical and others related to consumer, market or ethical issues. Public
      adoption of new technologies is an important determinant for their success. Many
      of the drivers behind the trend in personalisation of food are now known,
      particularly ethical, legal and social issues (ELSI) are the major drivers.
      Future development in the field of nutrigenomics undoubtedly will place its
      seemingly huge potential in better perspective. Thus, the agriculture and food
      enterprise has an extraordinary opportunity to link individuals with foods that
      are personalised for their health.

PMID- 19763658
TI  - Molecular aspects of somatic-to-embryogenic transition in plants.
AB  - Somatic embryogenesis (SE) is a model system for understanding the physiological,
      biochemical, and molecular biological events occurring during plant embryo
      development. Plant somatic cells have the ability to undergo sustained divisions
      and give rise to an entire organism. This remarkable feature is called plant cell
      totipotency. SE is a notable illustration of plant totipotency and involves
      reprogramming of development in somatic cells toward the embryogenic pathway.
      Plant growth regularities, especially auxins, are key components as their
      exogenous application recapitulates the embryogenic potential of the mitotically
      quiescent somatic cells. It has been observed that there are genetic and also
      physiological factors that trigger in vitro embryogenesis in various types of
      plant somatic cells. Analysis of the proteome and transcriptome has led to the
      identification and characterization of certain genes involved in SE. Most of
      these genes, however, are upregulated only in the late developmental stages,
      suggesting that they do not play a direct role in the vegetative-to-embryogenic
      transition. However, the molecular bases of those triggering factors and the
      genetic and biochemical mechanisms leading to in vitro embryogenesis are still
      unknown. Here, we describe the plant factors that participate in the vegetative
      to-embryogenic transition and discuss their possible roles in this process.

PMID- 19763659
TI  - Comparative study of clinical characteristics between Chinese Han and German
      Caucasian patients with coronary heart disease.
AB  - BACKGROUND: The differences of the clinical characteristics, risk factors,
      treatment and prognosis in coronary heart disease (CHD) patients from different
      races, area and countries are rarely reported. METHODS: Collecting, comparing and
      analyzing the clinical data and blood examination results of 650 Chinese Han and
      640 German Caucasian patients with CHD. RESULTS: The ratio of the first
      hospitalization because of CHD in Chinese patients was higher than that in
      Germans (95.1 vs. 38.1% P < 0.01). CHD occurred most frequently in elder men of
      both nations. The German CHD patients combined with hypertension, dyslipidemia
      and abnormal glucose metabolism were clearly more often than Chinese patients.
      Other risk factors such as fibrinogen, homocysteine and the proportion of
      positive family history of premature CHD, obesity, hyperuricemia were higher in
      German patients than that in Chinese patients. However, the ratio of smoking,
      acute myocardial infarction and the levels of high-sensitivity C-reactive protein
      in Chinese patients were obviously higher than that in Germans (P < 0.01, P <
      0.05). The use of aspirin in both groups was the same, but the use of statins,
      beta-blockers and angiotensin-converting enzyme inhibitors/angiotensin-receptor
      blockers were distinctly lower in Chinese patients compared to Germans (P < 0.01,
      P < 0.05). The proportion of percutaneous coronary intervention and coronary
      artery bypass grafting in Chinese patients was lower than that in Germans (P <
      0.01). The usage of drug-eluting stents to bare-metal stents was slightly higher
      in German patients, whereas it was obviously higher in Chinese patients (P <
      0.01). CONCLUSION: There were significant differences in clinical
      characteristics, risk factors and treatment of Chinese Han and German Caucasian
      patients with CHD.

PMID- 19763660
TI  - Pulmonary arteriovenous fistula in hereditary hemorrhagic  telangiectasis.

PMID- 19763661
TI  - Prognostic value of minimal blood flow restoration in patients with acute
      myocardial infarction after reperfusion therapy.
AB  - PURPOSE: The prognostic impact of low-flow reperfusion after percutaneous
      coronary intervention (PCI) in patients with ST-segment elevation acute
      myocardial infarction (STEMI) is unknown. The aim of the study was to investigate
      the impact of low-flow reperfusion after PCI in patients with STEMI. METHODS:
      This study included 1,761 patients with STEMI with a baseline thrombolysis in
      myocardial infarction (TIMI) flow grade 0 and no collateral circulation to the
      infarcted region before primary PCI. The primary outcome was 1-year mortality.
      RESULTS: At the end of PCI procedure there were 115 patients with post-PCI TIMI
      flow grade 0; 57 patients with TIMI flow grade 1; 218 patients with TIMI flow
      grade 2; and 1,371 patients with TIMI flow grade 3. At 1 year there were 36
      deaths in patients with TIMI grade 0; 28 deaths in patients with TIMI grade 1; 42
      deaths in patients with TIMI grade 2; and 162 deaths in patients with TIMI grade
      3 [estimates of mortality 32.6, 49.1, 19.6 and 12.1%, respectively; odds ratio
      (OR) = 1.76, 95% CI 1.08-2.86, P = 0.02, for TIMI flow grade 1 vs. TIMI flow
      grade 0]. The Cox proportional hazards model identified post-PCI TIMI flow grade
      as an independent predictor of 1-year mortality [hazard ratio (HR) = 1.99, 95% CI
      1.17-3.28; P = 0.01 for TIMI flow grade 1 vs. TIMI flow grade 0]. CONCLUSIONS:
      Patients with STEMI with totally occluded infarct-related arteries and no
      collateral blood flow to the infarcted region show a greater mortality with post
      PCI TIMI flow grade 1 than TIMI flow grade 0.

PMID- 19763662
TI  - DAOA/G72 predicts the progression of prodromal syndromes to first episode
      psychosis.
AB  - The genetic factors determining the progression of prodromal syndromes to first
      episode schizophrenia have remained enigmatic to date. In a unique prospective
      multicentre trial, we assessed whether variants at the D-amino acid oxidase
      activator (DAOA)/G72 locus influence progression to psychosis. Young subjects
      with a prodromal syndrome were observed prospectively for up to 2 years to assess
      the incidence of progression to schizophrenia or first episode psychosis. Of the
      82 probands with a prodromal syndrome, 21 probands experienced progression to
      psychosis within the observation period. Assessment of nine common variants in
      the DAOA/G72 locus yielded two variants with the predictive value for symptom
      progression: all four probands with the rs1341402 CC genotype developed psychosis
      compared with 17 out of 78 probands with the TT or CT genotypes (chi(2) = 12.348;
      df = 2; p = 0.002). The relative risk for progression to psychosis was
      significantly increased in the CC genotype: RR = 4.588 (95% CI = 2.175-4.588).
      Similarly, for rs778294, 50% of probands with the AA genotype, but only 22% of
      probands with a GG or GA genotype progressed to psychosis (chi(2) = 7.027; df =
      2; p = 0.030). Moreover, haplotype analysis revealed a susceptibility haplotype
      for progression to psychosis. This is one of the first studies to identify a
      specific genetic factor for the progression of prodromal syndromes to
      schizophrenia, and further underscores the importance of the DAOA/G72 gene for
      schizophrenia.

PMID- 19763663
TI  - Symptom clusters in obsessive-compulsive disorder (OCD): influence of age and age
      of onset.
AB  - Obsessive-compulsive disorder (OCD) is an ailment of heterogeneous nature. It is
      believed that the age of onset determines the subtype of juvenile OCD. The
      objective of our study was to evaluate the rates of symptoms' contents and the
      age of manifestation of the various OCD symptoms in adolescents and adults with
      early and late onset of disorder. Both authors independently reviewed the medical
      charts of patients treated for OCD between 1999 and 2007 in a psychiatric
      university hospital. Patients were evaluated using the Yale-Brown obsessive
      compulsive scale check list (Y-BOCS). The patients were grouped as adolescents
      (group 1), adults with late onset (group 2) and adults with early onset (group
      3). Chi2 was used for nominal variables and the non-parametric Kruskal-Wallis
      ANOVA for continuous comparisons due to deviations from normality of
      distribution. A total of 132 patients were enrolled in the study (44 group 1, 43
      group 2 and 45 group 3). There were no differences in gender distribution.
      Religious, sexual and miscellaneous obsessions were more frequent and somatic
      less frequent in group 1 than in group 2. Contamination compulsions were most
      seldom found in group 1. Cleaning obsessions were more frequent in group 3 than
      in group 1. Checking were the rarest and miscellaneous, the most often compulsion
      among adolescents in comparison to other groups. The symptoms' content in
      adolescents differed from those observed in adult, both with early and later
      onset of the disease. The age at onset influences the rates of adult patients'
      compulsions.

PMID- 19763664
TI  - Comparing the efficacy of stimulants for ADHD in children and adolescents using
      meta-analysis.
AB  - Stimulants used to treat attention-deficit/hyperactivity disorder (ADHD) have
      been well researched, but comparisons among stimulants are hindered by the
      absence of direct comparative trials. The goal of this work was to compare the
      efficacy of methylphenidate and amfetamine formulations through a meta-analysis
      of double-blind placebo-controlled trials. We analyzed recent published
      literature on the stimulant therapy of ADHD to describe the variability of drug
      placebo effect sizes. A literature search was conducted to identify double-blind,
      placebo-controlled studies of ADHD in children and adolescents published after
      1979. Meta-analysis regression assessed the influence of medication type and
      study design features on medication effects. Twenty-three trials met criteria and
      were included in this meta-analysis. These trials studied 11 drugs using 19
      different outcome measures of hyperactive, inattentive, or impulsive behavior. We
      found significant differences between amfetamine and methylphenidate products,
      even after correcting for study design features that might have confounded the
      results. Our analyses indicate that effect sizes for amfetamine products are
      significantly, albeit moderately, greater than those for methylphenidate. We
      found that most measures of effect from all studies were statistically
      significant. Our findings suggest that amfetamine products may be moderately more
      efficacious than methylphenidate products, even after controlling for potentially
      confounding study design features. This difference in effect size may be due to
      differences between amfetamine and methylphenidate in the molecular mechanisms
      involved in facilitating the dopaminergic neurotransmission.

PMID- 19763665
TI  - Course of intelligence deficits in early onset, first episode schizophrenia: a
      controlled, 5-year longitudinal study.
AB  - Only few prospective longitudinal studies have assessed the course of
      intelligence deficits in early onset schizophrenia (EOS), and these have used
      different age appropriate versions of Wechsler Intelligence Scales and age
      appropriate norms. The post-psychotic development of intelligence in EOS has
      predominantly been characterized as relatively stable in these studies. However,
      comparisons of IQs from different test versions based on the different norms may
      not permit unequivocal interpretations. The objective of the current study was to
      compare the development of intelligence in EOS patients (N = 10) from their first
      psychotic episode to 5 years of post onset with that of healthy controls (N = 35)
      and patients who at baseline had been diagnosed with other non-affective
      psychoses (N = 8). The same version of a Wechsler Intelligence Scale was
      administered at both baseline and follow-up assessments, and the same norms were
      used to derive IQs at baseline and follow-up. Significantly smaller change in
      mean full scale intelligence quotient (FSIQ) was found in diagnostically stable
      EOS patients compared with healthy controls during the follow-up period. However,
      no statistically significant difference in mean FSIQ change was observed between
      patients with EOS and patients with other non-affective psychoses, although this
      result must be interpreted with caution due to the small sample sizes. The
      results suggest abnormally slow acquisition of new intellectual information and
      skills in EOS patients during the first 5 years after full clinical presentation.

PMID- 19763666
TI  - Clinical characteristics and predictors of mortality in 67 patients with primary
      pyomyositis: a study from North India.
AB  - Primary pyomyositis is infection of the skeletal muscles in the absence of
      adjacent skin, soft tissue, and bone infection. This study was undertaken to look
      at the spectrum of clinical presentations, therapeutic interventions, and their
      outcomes and also to evaluate the association of various risk factors with
      mortality. This was a retrospective study in which the patients admitted with the
      diagnosis of primary pyomyositis from January 2000 to June 2007 were included.
      Their demographic details, clinical and laboratory data, Sequential Organ Failure
      Assessment (SOFA) score at presentation, treatment instituted, complications
      encountered, and hospital outcome were recorded. Sixty-seven patients (42 males
      and 25 females) with a diagnosis of primary pyomyositis were included. Median age
      at the time of presentation was 37 years (interquartile range = 25-50 years).
      Common presenting symptoms were myalgias [50 (74.62%)] and fever [49 (73.13%)].
      Twenty-six patients had underlying predisposing medical conditions. The commonest
      muscle group involved was iliopsoas muscles in 31 (46.26%) patients. Methicillin
      sensitive Staphylococcus aureus was the commonest organism isolated from the pus.
      Twenty-eight patients developed sepsis and seven died. On univariate analysis,
      there was a statistically significant association between higher SOFA score,
      lower Glasgow coma scale, higher pulse rate, lower blood pressure, raised blood
      urea, raised serum creatinine, higher serum glutamic pyruvate transaminase,
      raised total bilirubin at presentation, and development of sepsis during hospital
      stay with mortality. In our study, the patients were seen almost a decade later
      than those seen in other studies from the region. Evidence of organ dysfunction
      at presentation and sepsis was associated with increased mortality.

PMID- 19763667
TI  - Cyclosporine A-induced neck fibrosis in a patient with adult-onset Still's
      disease.
AB  - Cyclosporine A (CsA) is an immunosuppressive agent used for the prevention of
      graft rejection during organ and bone marrow transplantation. CsA is also used
      for the treatment of various inflammatory rheumatic diseases. Although different
      side effect profiles have been reported, nephrotoxicity, renal vascular damage,
      hypertension, and gingival hypertrophy are among the most commonly encountered
      side effects. The development of massive fibrosis in the neck associated with CsA
      in a 30-year-old male patient with Still's disease is presented herein.
      Significant regression was observed after the discontinuation of CsA.

PMID- 19763668
TI  - Evaluation of the furcation area permeability of deciduous molars treated by
      neodymium:yttrium-aluminum-garnet laser or adhesive.
AB  - The purpose of this in vitro study was to compare the effects of a self-etch
      adhesive system and neodymium:yttrium-aluminum-garnet (Nd:YAG) laser application
      on the dentinal permeability of the furcation area of primary molars. After
      endodontic access, 39 extracted human deciduous molars were divided into three
      groups: control group (CG), no treatment; adhesive group (AG), self-etching
      adhesive was applied to the furcation area; laser group (LG), specimens were
      irradiated with Nd:YAG laser. To evaluate dentin permeability of the furcation
      area, we immersed the specimens in 0.5 % methylene blue dye for 4 h. Then, they
      were longitudinally sectioned into two halves and photographed. The images were
      analyzed by two qualified evaluators using TpsDig software to calculate the
      percentage of the dye penetration area in comparison with the total furcation
      area. Additional analyses by scanning electron microscopy (SEM) were performed.
      The analysis of variance (ANOVA), complemented by Student's t-test, showed that
      mean dye penetration in the LG was statistically significant lower than that in
      all the other groups (P < 0.05). The SEM analysis showed mostly dentinal tubules
      obliterated by smear layer in the CG; in the AG the smear layer was modified by
      the adhesive, and, in the LG, melted surfaces were observed. It can be concluded
      that the Nd:YAG laser was capable of reducing the dentinal permeability of the
      furcation area of deciduous molars.

PMID- 19763669
TI  - Preliminary results on the use of a noninvasive instrument for the evaluation of
      the depth of pigmented skin lesions: numerical simulations and experimental
      measurements.
AB  - The early detection of cutaneous pigmented lesions is an important aid to the
      clinician in recognizing malignant melanoma. In an attempt to correlate the depth
      of a pigmented skin lesion with its malignant potential, phantoms able to
      simulate the diffuse reflectance of some lesions of different thicknesses were
      manufactured and tested to validate a diagnostic instrument developed in-house.
      Such optical skin-tissue phantoms may be useful for accelerating and optimizing
      the diagnosis of suspicious lesions of the skin. In fact, benign melanocytic
      lesions are different in terms of their diffuse reflectance from melanoma. The
      diffuse reflectance of pigmented skin lesions depends on the amount and
      distribution of the absorbing/diffusing chromophores embedded in the skin layers.
      The basic phantom material is a PVA hydrogel in which appropriate amounts of
      optical scatter are added extraneously at the time of formation to achieve
      tunability of the optical properties. Liquid Indian ink is used to simulate
      melanin and all the other chromophores. Slabs were prepared to mimic lesions of
      different depths. The optical properties of the tissue phantoms were determined
      in the visible and near-infrared spectral ranges using a noninvasive instrument
      made from a purpose-modified digital camera. The measured reflectance was
      correlated with the depth of the lesion both in a Monte Carlo simulation
      environment and in a laboratory experiment.

PMID- 19763670
TI  - An orlistat "overdose" in a child.

PMID- 19763671
TI  - Preliminary analysis of demographics and learning attributes of graduate entry
      medical students.
AB  - INTRODUCTION: Students entering university are empowered to move towards self
      directed professional learning and beyond didactic tuition. Graduate entry
      medical (GEM) students have prior experience of this transition from pedagogical
      to androgogical learning. We aimed to assess the demographics and learning
      attributes of GEM students. METHODS: Ethical exemption was awarded. The short
      version of the approaches and study skills inventory for students and the
      learning style questionnaire were distributed to GEM students during semester 1,
      2008. RESULTS: Response rate was 84% (n = 32). Fifty percent of responders had
      graduated in 2008 (22%) or 2007 (28%). Seventy-five percent had a background in
      basic science (56%) or an allied health profession (19%). The predominant
      learning approach is a combination of deep and strategic. The predominant
      learning style is reflective. CONCLUSIONS: Our preliminary analysis reveals GEM
      students to exhibit a mature approach to learning and the requisite learning
      style to achieve academic and clinical success.

PMID- 19763672
TI  - Swimming in ice cold water.
AB  - INTRODUCTION: We investigated two athletes swimming in 4 degrees C for 23 min
      (1.3 km, swimmer 1) and 42 min (2.2 km, swimmer 2), respectively. MATERIALS AND
      METHODS: Pre swim, percent body fat was determined; post swim, core temperature
      was measured. RESULTS: The core temperature of swimmer 2 was: 37.0 degrees C
      immediately before the start, 32 degrees C 20 min after getting out of the water,
      and 35.5 degrees C 80 min after finishing the swim. CONCLUSION: We assume that
      the higher skin-fold thickness and body fat of swimmer 2 enabled him to perform
      longer. In addition to this, mental power and experience in cold water swimming
      must be considered. In any athlete aiming at swimming in water of less than 5
      degrees C, body core temperature and heart rate should be continuously monitored
      in order to detect a body core temperature below 32 degrees C and arrhythmia to
      pull the athlete out of the water before life-threatening circumstances occur.

PMID- 19763673
TI  - Inappropriate use of proton pump inhibitors.
AB  - BACKGROUND: Proton pump inhibitors (PPIs) are widely used expensive medications.
      AIMS: We performed a cross-sectional study to determine the extent and indication
      of PPI use in Irish acute medical wards. METHODS: Fifty-five medical charts were
      reviewed at the beginning and end of 1 month. RESULTS AND CONCLUSIONS: Thirty
      three patients were prescribed PPIs; 26 prior to admission. The prescribing of
      PPIs was concordant with guideline recommendations in only 30% of cases. Two
      thirds of PPI use was unlicensed.

PMID- 19763674
TI  - Sustained weight loss and improvement of quality of life after laparoscopic
      adjustable gastric banding for morbid obesity: a single surgeon experience in
      Ireland.
AB  - BACKGROUND: Although substantial weight loss is the primary outcome following
      bariatric surgery, changes in obesity-related morbidity and quality of life (QoL)
      are equally important. This study reports on weight loss, QoL and health outcomes
      following laparoscopic adjustable gastric banding (LAGB). METHODS: Bariatric
      analysis and reporting outcome system questionnaire survey was carried out on
      patients who had LAGB. Patients' body weight, body mass index, QoL and co
      morbidities were recorded. RESULTS: Twenty-three of 26 patients answered the
      questionnaire (response rate of 92%). Fifteen patients (60%) achieved over 50%
      excess weight loss. Twenty-two patients (84.6%) reported improvement in QoL. Co
      morbidities in 18 patients (75%) resolved or improved. One patient had
      postoperative aspiration pneumonia and no other morbidity was recorded.
      CONCLUSIONS: Laparoscopic adjustable gastric banding is a safe and feasible
      method of bariatric surgery. It can achieve satisfactory weight loss with
      significant improvement in QoL and co-morbidity provided patients undergo
      thorough preoperative preparation and rigorous postoperative follow-up.

PMID- 19763675
TI  - Pap smears for men: a vision of the future?
AB  - BACKGROUND: Anal intraepithelial neoplasia (AIN) rarely receives as much
      publicity as its neighbouring orifice, the cervix. As in the cervix,
      intraepithelial neoplasias are precursors to cancer in the anal canal. AIN and
      cervical interstitial neoplasia (CIN) undergo dysplasia as a consequence of human
      papillomavirus (HPV) infection. Since the advent of screening with the Pap smear
      in CIN, cervical cancer has plummeted to a fifth of its initial incidence. Anal
      cancer, however, has been rising, with a predilection for human immunodeficiency
      virus-infected men. HPV causes a squamous epithelial dysplasia and converts
      healthy tissue into AINs of increasing severity until anal cancer manifests.
      CLINICAL CASE: This article describes a clinical case of anogenital HPV infection
      refractory to medical and surgical therapy. It also describes an effective
      surgical excision technique associated with a good cosmetic outcome. CONCLUSIONS:
      The paper concludes by briefly discussing the implications of a national
      screening programme against AIN in the future.

PMID- 19763676
TI  - Trace element concentrations (mercury, cadmium, copper, zinc, lead, aluminium,
      nickel, arsenic, and selenium) in some aquatic birds of the southwest Atlantic
      coast of France.
AB  - Trace elements (mercury [Hg], cadmium [Cd], copper [Cu], zinc [Zn], lead [Pb],
      aluminium [Al], nickel [Ni], arsenic [As], and selenium [Se]) were investigated
      using inductively coupled plasma-mass spectrometry in liver, kidney, muscle, and
      feather of aquatic birds wintering or inhabiting the wetlands situated on the
      Southwest Atlantic coast of France. A majority of greylag geese, red knots, and
      grey plovers were collected from among hunter-shot animals. The relation between
      residue concentrations, age (juvenile vs. adult), and sex was investigated. Trace
      elements were lower than threshold levels of toxicity, except for Pb. Greylag
      geese sampled could be considered Pb-poisoned. These consequential levels of
      contamination could be the result of the ingestion of Pb-shot from ammunition
      used in hunting areas they crossed during migration. Cd accumulation increased
      with age, whereas Pb levels in feathers were lower in adult birds in connection
      with moulting. As was influenced by sex. Female birds displayed higher
      concentrations in liver and feathers than did male birds.

PMID- 19763677
TI  - Effects of dietary selenomethionine on cutthroat trout (Oncorhynchus clarki
      bouvieri) growth and reproductive performance over a life cycle.
AB  - A 2.5-year feeding trial was conducted in which cutthroat trout (Oncorhynchus
      clarki bouvieri) were fed either a basal diet (1.2 microg Se/g diet) or the basal
      diet supplemented with 2, 4, 6, 8, or 10 microg Se/g diet as selenomethionine
      from 1 g weight to maturation [corrected]. After 44 weeks of feeding, a subsample
      of fish was removed from dietary treatment groups and fed the basal diet for an
      additional 32 weeks. Concentrations of Se in whole fish and eggs increased in
      proportion to dietary Se intake, but no differences in growth, feed intake,
      survival, or egg hatchability were observed among dietary groups. Cranial-facial
      deformities in second-generation offspring were less than 6% in all treatment
      groups except for fish fed the diet supplemented with 4 microg Se/g diet as
      selenomethionine [corrected], where a 9.2% incidence was observed. Fish switched
      from selenomethionine-supplemented diets to the basal diet lost Se, calculated as
      microg Se lost/g weight gain, at 1.01, 2.84, 4.42, and 4.42 for dietary treatment
      groups 3, 4, 5, and 6, respectively. Results suggest no toxicity of dietary
      selenomethionine up to 10 microg/g supplemented diet and that with total life
      cycle exposure, cutthroat trout increase Se excretion to maintain whole-body
      concentrations below toxic levels.

PMID- 19763678
TI  - Comparison of polycyclic aromatic hydrocarbons levels in sludges from municipal
      and industrial wastewater treatment plants.
AB  - This study was carried out to investigate the concentrations and potential
      sources of the polycyclic aromatic hydrocarbons (PAHs) in sludge of 14 wastewater
      treatment plants (WWTPs). Sludge samples were collected from 2 municipal WWTPs,
      11 industrial WWTPs, and 1 sanitary landfill leachate treatment plant within the
      city of Bursa, Turkey during the summer of 2008. Ultrasonication was applied for
      extraction and gas chromatography-mass spectrometry was used to analyze the PAH
      contents of the samples. Twelve of the 16 EPA-listed PAH compounds were
      determined. Total PAH concentrations (Sigma(12) PAHs) determined in all of the
      sludge samples ranged from 1,781 to 19,866 microg/kg dry matter (dm). The sum of
      8 of the 11 EU PAHs varied between 1,481 and 17,314 microg/kg dm, and 3 of the
      samples exceeded the proposed EU limit for land application. One of the
      automotive industry sludges contained the highest level of PAHs, followed by one
      of the municipal sludges. The average sum of 5- and 6-ring PAH compounds in all
      of the sludge samples amounted to almost 65% of the total PAHs. The diagnostic
      ratios of specific PAHs were calculated to determine the dominant sources for the
      PAHs in the sludge samples.

PMID- 19763679
TI  - Occurrence of organic wastewater and other contaminants in cave streams in
      northeastern Oklahoma and northwestern Arkansas.
AB  - The prevalence of organic wastewater compounds in surface waters of the United
      States has been reported in a number of recent studies. In karstic areas, surface
      contaminants might be transported to groundwater and, ultimately, cave
      ecosystems, where they might impact resident biota. In this study, polar organic
      chemical integrative samplers (POCISs) and semipermeable membrane devices (SPMDs)
      were deployed in six caves and two surface-water sites located within the Ozark
      Plateau of northeastern Oklahoma and northwestern Arkansas in order to detect
      potential chemical contaminants in these systems. All caves sampled were known to
      contain populations of the threatened Ozark cavefish (Amblyopsis rosae). The
      surface-water site in Oklahoma was downstream from the outfall of a municipal
      wastewater treatment plant and a previous study indicated a hydrologic link
      between this stream and one of the caves. A total of 83 chemicals were detected
      in the POCIS and SPMD extracts from the surface-water and cave sites. Of these,
      55 chemicals were detected in the caves. Regardless of the sampler used, more
      compounds were detected in the Oklahoma surface-water site than in the Arkansas
      site or the caves. The organic wastewater chemicals with the greatest mass
      measured in the sampler extracts included sterols (cholesterol and beta
      sitosterol), plasticizers [diethylhexylphthalate and tris(2-butoxyethyl)
      phosphate], the herbicide bromacil, and the fragrance indole. Sampler extracts
      from most of the cave sites did not contain many wastewater contaminants,
      although extracts from samplers in the Oklahoma surface-water site and the cave
      hydrologically linked to it had similar levels of diethylhexyphthalate and common
      detections of carbamazapine, sulfamethoxazole, benzophenone, N-diethyl-3
      methylbenzamide (DEET), and octophenol monoethoxylate. Further evaluation of this
      system is warranted due to potential ongoing transport of wastewater-associated
      chemicals into the cave. Halogenated organics found in caves and surface-water
      sites included brominated flame retardants, organochlorine pesticides (chlordane
      and nonachlor), and polychlorinated biphenyls. The placement of samplers in the
      caves (near the cave mouth compared to farther in the system) might have
      influenced the number of halogenated organics detected due to possible aerial
      transport of residues. Guano from cave-dwelling bats also might have been a
      source of some of these chlorinated organics. Seven-day survival and growth
      bioassays with fathead minnows (Pimephales promelas) exposed to samples of cave
      water indicated initial toxicity in water from two of the caves, but these
      effects were transient, with no toxicity observed in follow-up tests.

PMID- 19763681
TI  - Small hepatocellular carcinoma with bile duct tumor thrombi: CT and MRI findings.
AB  - BACKGROUND: Small hepatocellular carcinoma (sHCC) with bile duct tumor thrombi
      (BDTT) is rare and easily misdiagnosed as cholangiocarcinoma. This study was to
      analyze the imaging features of sHCC with BDTT. PATIENTS AND METHODS: CT and/or
      MRI examinations were performed on seven patients who had sHCC with BDTT. One
      patient received CT scan, one received CT and MR scan, and five received MR scan.
      Magnetic resonance cholangiopancreatography (MRCP) was performed in five
      patients. The diagnosis of sHCC with BDTT was based on surgical specimens in all
      patients. RESULTS: The sHCC lesions and BDTT were presented on CT or MRI scans in
      all the seven cases. The BDTT is presented as soft tissue mass in the bile duct
      with biliary dilatation above the obstruction. In the two patients who had
      received dynamic contrast CT scan, the sHCC lesions showed atypical enhancement
      pattern of HCC. The BDTT showed similar enhancement pattern as sHCC in one of the
      two patients. The sHCC and BDTT showed homogenous hypointense signals on T1W
      images and hyperintense signals on T2W images in all six cases. In the three
      patients who had received dynamic enhancement MR scan, the enhancement patterns
      of sHCC lesions and BDTT were similar. Early enhancement of sHCC lesion and BDTT
      at hepatic arterial phase with hyperintense signals was observed in one patient,
      while two other patients had no early enhancement. All sHCC lesions and BDTT
      showed hypointense signals at portal venous phase, equilibrium phase, and delayed
      phase. Six patients showed hyperintense signal of hemorrhage in the dilated bile
      ducts on both T1W and T2W images. Five cases of BDTT presented as filling defect
      in the bile ducts on MRCP. The BDTT were directly connected with sHCC lesions in
      all the seven patients, without bile duct wall thickening or extra-bile duct
      invasion. CONCLUSION: CT or MRI is a safe, reliable, and valuable method for the
      detection and diagnosis of sHCC with BDTT.

PMID- 19763680
TI  - Francisella novicida forms in vitro biofilms mediated by an orphan response
      regulator.
AB  - Francisella tularensis is associated with water and waterways and infects many
      species of animals, insects, and protists. The mechanism Francisella utilizes to
      persist in the environment and in tick vectors is currently unknown. We have
      demonstrated for the first time that Francisella novicida, a model organism of F.
      tularensis, forms a biofilm in vitro. Selected F. novicida transposon mutants
      were tested for their ability to form biofilm compared to the wildtype F.
      novicida strain. Mutation of the putative qseB gene led to an impairment in the
      ability to form biofilm with no impairment in bacterial growth. A qseC mutant had
      impaired growth but demonstrated a marked impairment in biofilm production.
      Mutation in capC affected both bacterial growth and biofilm formation, but no
      biofilm production impairment was seen with capB or pilE mutants. A deletion
      mutant in the orphan response regulator FTN_1465, which we propose is the
      putative QseB, formed significantly less biofilm than the wildtype. When FTN_1465
      was complemented back into the deletion mutant, biofilm formation was restored.
      Thus, the orphan response regulator FTN_1465 is an important factor in biofilm
      production in vitro in F. novicida. These results demonstrate that Francisella
      species are able to form biofilms in vitro, suggesting that biofilm formation may
      be important for the lifecycle of this organism.

PMID- 19763682
TI  - Comparison of CT colonography vs. conventional colonoscopy in mapping the
      segmental location of colon cancer before surgery.
AB  - Once presence of a colorectal cancer has been diagnosed, a key factor for
      patient's prognosis in view of surgical intervention is the correct segmental
      localization and resection of the tumor. The aim of this work was to compare the
      accuracy of the current gold standard technique, conventional colonoscopy (CC),
      to computed tomography colonography (CTC) in the segmental localization of tumor.
      Sixty-five patients (mean age 64; 45 female and 19 male) with colorectal cancer
      diagnosed at colonoscopy underwent CTC before surgery. In 45 out of 65 cases
      (69%), patients were referred to CTC after incomplete CC. Reasons were patient
      intolerance to CC or presence of stenosing cancer, with consistent difficulties
      in crossing the tract of the colon involved by the lesion. CTC allowed the
      complete colonic examination in 63/65 cases, since in 2 patients with an
      obstructing lesion of the sigmoid colon, pneumocolon could not be obtained.
      However, per patient and per lesion sensitivity of CTC was 100%. Difference from
      colonoscopy was statistically significant (P < 0.05). In terms of segmental
      localization of masses, CTC located precisely all lesions, while colonoscopy
      failed in 16/67 (24%) lesions, though six were missed for incomplete colonoscopy
      (9%). In the remaining 10/67 (15%) lesions, detected by colonoscopy but
      incorrectly located, the mismatch occurred in the rectum (n = 3), sigmoid (n =
      2), descending (n = 1), transverse (n = 2), ascending colon, and cecum. Agreement
      between CTC and CC was fair (k value 0.62). Sensitivity, specificity, positive
      predictive value and negative predictive value of CTC in determining the precise
      location of colonic masses were respectively 100%, 96%, 85%, and 100%. CT
      detected hepatic (6/65 patients) and lung metastases (3/65 patients). CT
      colonography has better performance in the identification of colonic masses
      (diameter > 3 cm), in the completion of colonic evaluation and in the segmental
      localization of tumor. CTC should replace colonoscopy for preoperative staging of
      colorectal cancer.

PMID- 19763683
TI  - Angiogenesis of renal cell carcinoma: perfusion CT findings.
AB  - OBJECTIVE: To observe the perfusion CT findings of renal cell carcinoma (RCC) and
      prospectively correlate perfusion CT parameters with tumor MVD and VEGF
      expression. METHODS: Dynamic contrast-enhanced multislice spiral CT was performed
      prospectively in 73 cases with histologically proven RCC (65 clear cell, 3
      papillary, and 5 chromophobe). Blood flow (BF), blood volume (BV), mean transit
      time (MTT), and permeability surface-area product (PS) of RCC and normal renal
      cortex were measured, respectively. The tumor MVD count and VEGF expression level
      were determined by immunohistochemistry with specific monoclonal antibodies.
      RESULTS: There was significant difference between BF, BV, MTT, and PS of normal
      renal cortex (454.32 +/- 110.90 mL/min/100 g, 23.53 +/- 5.71 mL/100 g, 3.62 +/-
      1.38 s, 63.95 +/- 18.85 mL/min/100 g) and RCC (261.96 +/- 175.86 mL/min/100 g,
      17.17 +/- 8.34 mL/100 g, 7.08 +/- 3.42 s, 25.07 +/- 13.20 mL/min/100 g) (P <
      0.01). BF and BV among RCC histologic subtypes were significantly different (P <
      0.05), MTT and PS were not (P > 0.05). MVD (42.29 +/- 21.00) of RCC is positively
      correlated with BF, BV, and PS (P < 0.01), not with MTT (P > 0.05). No
      relationship was found between the expression levels of VEGF and any perfusion CT
      parameter. CONCLUSIONS: Perfusion CT is a feasible technique to assess tissue
      perfusion in patients with RCC. BV, BF, and PS correlate positively with MVD and
      may reflect angiogenesis of RCC.

PMID- 19763684
TI  - A comparative approach for ranking contaminated sites based on the risk
      assessment paradigm using fuzzy PROMETHEE.
AB  - A ranking system for contaminated sites based on comparative risk methodology
      using fuzzy Preference Ranking Organization METHod for Enrichment Evaluation
      (PROMETHEE) was developed in this article. It combines the concepts of fuzzy sets
      to represent uncertain site information with the PROMETHEE, a subgroup of Multi
      Criteria Decision Making (MCDM) methods. Criteria are identified based on a
      combination of the attributes (toxicity, exposure, and receptors) associated with
      the potential human health and ecological risks posed by contaminated sites,
      chemical properties, site geology and hydrogeology and contaminant transport
      phenomena. Original site data are directly used avoiding the subjective
      assignment of scores to site attributes. When the input data are numeric and
      crisp the PROMETHEE method can be used. The Fuzzy PROMETHEE method is preferred
      when substantial uncertainties and subjectivities exist in site information. The
      PROMETHEE and fuzzy PROMETHEE methods are both used in this research to compare
      the sites. The case study shows that this methodology provides reasonable
      results.

PMID- 19763685
TI  - Minimally invasive parathyroidectomy: benefits and requirements of localization,
      diagnosis, and intraoperative PTH monitoring. long-term results.
AB  - BACKGROUND: Surgery is the only curative treatment for primary
      hyperparathyroidism. Initial parathyroidectomy procedures fail due to ectopic
      gland location and unappreciated multigland disease. METHODS: An evidence-based
      literature review was performed,which surveyed all human studies in PubMed,
      searching for parathyroidectomy in humans between 1990 and 2009. Between 10 and
      30% of patients have multigland disease caused by double adenomas or hyperplasia.
      Use of preoperative imaging studies and intraoperative PTH monitoring helps
      parathyroid surgeons overcome these obstacles. RESULTS: Sestamibi nuclear scan
      and neck ultrasound identify 70-80% of abnormal glands in patients with single
      adenomas. The sensitivity of ultrasound or sestamibi to identify all abnormal
      glands in patients with multigland disease is extremely low. Intraoperative PTH
      monitoring should be utilized in all patients who undergo neck exploration for
      primary hyperparathyroidism to reduce failures due to multigland disease. Blood
      samples should be drawn from peripheral veins only and a postresection level 10
      15 min after gland removal should have a >50%decrease from baseline preoperative
      levels, and also must go to the normal range for the PTH assay being used.
      CONCLUSIONS: Contemporary prospective studies (level of evidence III/IV) show
      that by combining preoperative imaging and IOPTH it is possible to maximize
      performance of successful outpatient minimally invasive parathyroidectomy.

PMID- 19763686
TI  - Systematic review and meta-analysis of chewing-gum therapy in the reduction of
      postoperative paralytic ileus following gastrointestinal surgery.
AB  - BACKGROUND: Postoperative ileus has long been considered an inevitable
      consequence of gastrointestinal surgery. It prolongs hospital stay, increases
      morbidity, and adds to treatment costs. Chewing is a form of sham feeding
      reported to stimulate bowel motility. This analysis examines the value of chewing
      gum therapy in treatment of postoperative ileus. METHODS: A search for
      randomized, controlled trials studying elective gastrointestinal surgery was
      undertaken using MEDLINE, Embase, Cochrane Controlled Trials Register, and
      reference lists. Outcomes were extracted including time to first flatus and bowel
      motion, length of stay, and complications. Statistical analysis was undertaken
      using the weighted mean difference (WMD) and random-effects model with 95%
      confidence intervals (CI). RESULTS: Seven studies with 272 patients were
      included. For time to first flatus the analysis favored treatment with a WMD of
      12.6 h (17%) reduction (95% CI -21.49 to -3.72; P = 0.005). For time to first
      bowel motion, treatment was favored with a WMD of 23.11 h (22%) reduction (95% CI
      -34.32 to -11.91; P < 0.001). For length of stay, the analysis showed a
      nonsignificant trend toward treatment with WMD of 23.88 h (12%) reduction (95% CI
      -53.29 to +5.53; P = 0.11). There were no significant differences in complication
      rates. CONCLUSIONS: Chewing-gum therapy following open gastrointestinal surgery
      is beneficial in reducing the period of postoperative ileus, although without a
      significant reduction in length of hospital stay. These outcomes are not
      significant for laparoscopic gastrointestinal surgery.

PMID- 19763688
TI  - NHLBI workshop: respiratory medicine-related research training for adult and
      pediatric fellows.
AB  - The pulmonary physician-scientist has a special niche to generate basic research
      findings and apply them to a clinical disease and perhaps impact its medical
      care. The availability of new high throughput-based scientific technologies in
      the "omics era" has made this an opportune time for physician scientists to
      prepare and embark on an academic career in respiratory disease research.
      However, maintaining an adequate flow through the research pipeline of physician
      scientist investigators studying respiratory system diseases is currently a
      challenge. There may not be a sufficient workforce emerging to capitalize on
      current research opportunities. The National Heart, Lung, and Blood Institute
      (NHLBI) organized a workshop to assess ways to attract and properly train
      advanced fellows to pursue research careers in adult and pediatric lung diseases.
      Participants included representatives from the various pulmonary training
      programs, respiratory-related professional societies, and NHLBI staff.
      Deliberation centered on present barriers that might affect interest in pursuing
      research training, devising better incentives to attract more trainees, and how
      current research support offered by the NHLBI and the Professional Societies (in
      partnership with Industry and Patient Support groups) might be better coordinated
      and optimized to ensure a continued pipeline of pulmonary investigators. Major
      recommendations offered are: (1) Attract trainees to pulmonary/critical care
      medicine-based research careers by increasing research exposure and opportunities
      for high school, college, and medical students. (2) Increase awareness of the
      outstanding physician-scientist role models in the lung community for trainees.
      (3) Facilitate mechanisms by which the lung community (NHLBI, professional
      societies, and partners) can better support and bridge senior fellows as they
      transition from Institutional Training Grants (T32) to Career Series (K) awards
      in their early faculty career development.

PMID- 19763687
TI  - Interindividual variation in epigenomic phenomena in humans.
AB  - Our knowledge of regulatory mechanisms of gene expression and other chromosomal
      processes related to DNA methylation and chromatin state is continuing to grow at
      a rapid pace. Understanding how these epigenomic phenomena vary between
      individuals will have an impact on understanding their broader role in
      determining variation in gene expression and biochemical, physiological, and
      behavioural phenotypes. In this review we survey recent progress in this area,
      focusing on data available from humans. We highlight the role of obligatory
      (sequence-dependent) epigenomic variation as an important mechanism for
      generating interindividual variation that could impact our understanding of the
      mechanistic basis of complex trait architecture.

PMID- 19763689
TI  - Oropharyngeal dysphagia in infants and children with infantile Pompe disease.
AB  - Pompe disease is a rare genetic progressive neuromuscular disorder. The most
      severe form, infantile Pompe disease, has historically resulted in early
      mortality, most commonly due to cardiorespiratory failure. Treatment with enzyme
      replacement therapy (ERT) using alglucosidase alfa (Myozyme((r))) has extended
      the lifespan of individuals with this disease. With the introduction of ERT and
      the resultant improved survival, dysphagia is being encountered clinically with
      increasing regularity though systematic data remain unavailable. We
      retrospectively studied the oropharyngeal swallowing of 13 infants and children
      with Pompe disease using videofluoroscopy before initiation of ERT, allowing for
      baseline swallow function to be established in an untreated cohort. Dysphagia was
      present in all 13 subjects, even in a participant only 15 days old. Oral stage
      signs were present in 77%, most frequently a weak suck in 69%. Pharyngeal stage
      signs were present in 100%, including a pharyngeal swallow delay in 92% and
      pharyngeal residue in 77%. Airway invasion was present in 76.9% of subjects,
      including penetration in five (38.46%) and silent aspiration in an additional
      five (38.46%). No relationship in the relative involvement of swallowing, gross
      motor function, and cardiac disease appeared to be present.

PMID- 19763690
TI  - Umbrella and roll-up techniques of mesh insertion for laparoscopic hernia repair:
      a comparative study.
AB  - BACKGROUND: Deploying a mesh during laparoscopic hernia repair can be difficult
      and possibly challenging for a trainee surgeon. METHODS: A novel method of mesh
      insertion by folding the mesh like the fabric of an umbrella and loading it into
      the 10-mm cannula for delivery into the peritoneal cavity is described. This
      method uses the inherent ability of meshes to spring back into shape. In this
      study on 30 patients who underwent transabdominal preperitoneal hernia repair,
      the umbrella method of mesh insertion was compared with the traditional roll up
      type of mesh insertion in terms of easiness mesh deployment and operating time.
      In bilateral procedures, each side was considered as a separate operation.
      RESULTS: The operative time for the mesh insertion was reduced slightly (6 min),
      from 18 min for the roll-up technique to 12 min for the umbrella technique.
      CONCLUSION: The umbrella method has a distinct advantage over the roll-up
      technique, in which unrolling of the mesh is done in a plane parallel to the
      mesh. This may explain the time saved, as demonstrated in this pilot study.

PMID- 19763691
TI  - Comodulation masking release determined in the mouse (Mus musculus) using a
      flanking-band paradigm.
AB  - Comodulation masking release (CMR) has been attributed to auditory processing
      within one auditory channel (within-channel cues) and/or across several auditory
      channels (across-channel cues). The present flanking-band (FB) experiment-using a
      25-Hz-wide on-frequency noise masker (OFM) centered at the signal frequency of 10
      kHz and a single 25-Hz-wide noise FB-was designed to separate the amount of CMR
      due to within- and across-channel cues and to investigate the role of temporal
      cues on the size of within-channel CMR. The results demonstrated within-channel
      CMR in the Naval Medical Research Institute mouse, while no unambiguous evidence
      could be found for CMR occurring due to across-channel processing (i.e., "true
      CMR"). The amount of within-channel CMR was dependent on the frequency separation
      between the FB and the OFM. CMR increased from 4 to 6 dB for a frequency
      separation of 1 kHz to 18 dB for a frequency separation of 100 Hz. The large
      increase for a frequency separation of 100 Hz is likely to be due to the
      exploitation of changes in the temporal pattern of the stimulus upon the addition
      of the signal. Temporal interaction between both masker bands results in
      modulations with a large depth at a modulation frequency equal to the beating
      rate. Adding a signal to the maskers reduces the depth of the modulation. The
      auditory system of mice might be able to use the change in modulation depth at a
      beating frequency of 100 Hz as a cue for signal detection, while being unable to
      detect changes in modulation depth at high modulation frequencies. These results
      are consistent with other experiments and model predictions for CMR in humans
      which suggested that the main contribution to the CMR effect stems from
      processing of within-channel cues.

PMID- 19763692
TI  - Validation of the pedigree assessment tool (PAT) in families with BRCA1 and BRCA2
      mutations.
AB  - BACKGROUND: The lifetime risk of breast cancer (BC) in patients with hereditary
      breast cancer syndromes is as high as 80%. The Pedigree Assessment Tool (PAT) is
      a scoring system to aid in identifying these patients. This validation study
      compares the PAT to BRCA gene mutation probability models in predicting
      suitability for genetic referral. METHODS: Retrospective review identified
      subjects undergoing genetic counseling and BRCA testing from 2001 to 2008 at two
      institutions. PAT score and BRCA mutation probabilities were calculated using
      Myriad II and Penn II models. Comparisons were made between models in ability to
      discriminate patients appropriate for genetic evaluation based on accuracy in
      predicting a positive test result. RESULTS: Records evaluated represent 520
      families. BRCA testing revealed 146 mutation-positive and 374 mutation-negative
      families. c-Statistic analysis was used to compare the discriminating ability of
      the models to correctly assign families as mutation (+) and (-). Both the PAT and
      Penn II model outperformed the Myriad II model. Using a threshold PAT score >or=8
      and mutation probability >or=10% to assign families as mutation (+) versus (-),
      sensitivity, specificity, and positive and negative predictive values were
      calculated for each model. The PAT was more sensitive than the Myriad II model
      and more specific than the Penn II model. CONCLUSIONS: In overall performance,
      the PAT is at least comparable to the Myriad II and Penn II models in screening
      women appropriate for genetic referral. Simplicity and identification of families
      with non-BRCA hereditary BC syndromes suggest that the PAT is better suited for
      BC risk screening.

PMID- 19763693
TI  - Extended lymph node dissection for rectal cancer with radiologically diagnosed
      extramesenteric lymph node metastasis.
AB  - BACKGROUND: The purpose of this study is to review the clinical outcomes of
      patients who received extended lymph node dissection for radiologically diagnosed
      extramesenteric lymph node metastasis. PATIENTS AND METHODS: The authors reviewed
      clinical characteristics, short-term operative outcomes, and long-term oncologic
      outcomes of 151 patients who had received total mesorectal excision plus extended
      lymph node dissection for the treatment of radiologically diagnosed
      extramesenteric lymph node metastasis. RESULTS: The positive predictive value of
      the radiologic diagnosis of extramesenteric lymph node metastasis was 86.4% for
      lateral nodes and 40.0% for para-aortic nodes. It showed improvement over time.
      Perioperative mortality occurred in 3 patients (2.0%) and morbidity in 31
      patients (20.5%). Pathologic examinations revealed metastatic para-aortic lymph
      nodes in 43 patients (PA) and metastatic lateral pelvic nodes in 36 patients
      (LP), while in 21 patients, metastasis was found in both (LP + PA). Both cancer
      specific survival (CSS) and disease-free survival (DFS) were significantly
      different according to the extent of node metastasis (CSS: P < .001; DFS: P <
      .001) and univariate and multivariate analyses for prognostic factors revealed
      that the lymph node status as to location was the only factor. CONCLUSION:
      Patients with extramesenteric lymph node metastasis may be a distinct subgroup
      with poor prognosis. Extended lymph node dissection may have a role for those
      patients. However, the optimal treatment strategy remains inconclusive, for which
      further clinical research is necessary.

PMID- 19763694
TI  - Prognostic impact of RT-PCR-based detection of peritoneal micrometastases in
      patients with pancreatic cancer undergoing curative resection.
AB  - BACKGROUND: Positive peritoneal fluid cytology predicts poor outcome in patients
      with resected pancreatic cancer. Reverse transcription-polymerase chain reaction
      (RT-PCR) has been proposed as a more sensitive means of detection of peritoneal
      micrometastases than conventional cytology. The clinical significance of RT-PCR
      positivity in the absence of other evidence of peritoneal disease is unknown. The
      purpose of the current study was to determine the outcome RT-PCR
      positive/cytology-negative patients who underwent potentially curative resection.
      METHODS: Peritoneal washings were collected prospectively from 115 patients with
      pancreatic cancer undergoing diagnostic laparoscopy at a single institution.
      Specimens were analyzed by a cytopathologist and by RT-PCR for carcinoembryonic
      antigen (CEA). RESULTS: Of the 115 patients, 62 (54%) underwent R0 resection.
      Eleven of the 62 patients (18%) had peritoneal washings that were negative by
      conventional cytology but positive for CEA by RT-PCR. Those 11 patients
      experienced early peritoneal and overall disease recurrence versus those who were
      RT-PCR negative (P = 0.001, P = 0.003, respectively) independent of nodal status.
      CONCLUSIONS: RT-PCR for CEA is a sensitive and specific method for the detection
      of clinically significant peritoneal micrometastases from pancreatic cancer and
      it might identify a subgroup of patients with otherwise negative findings at
      staging laparoscopy who might respond better to treatment other than primary
      surgical resection.

PMID- 19763695
TI  - Vascular endothelial growth factor: an essential component of angiogenesis and
      fracture healing.
AB  - Fractures require adequate stability and blood supply to heal. The vascular
      supply to long bones is compromised in a fracture, and the ability to heal hinges
      on the ability of new blood vessels to proliferate from surrounding vessels in a
      process known as angiogenesis. This process is largely driven by the growth
      factor, vascular endothelial growth factor (VEGF), whose levels are increased
      locally and systemically during fracture healing. VEGF is involved in many steps
      throughout the fracture healing cascade, from initially being concentrated in
      fracture hematoma, to the promotion of bone turnover during the final remodeling
      phase. This article reviews the current literature surrounding the role of VEGF
      and other growth factors in reestablishing vascular supply to fractured bone, as
      well as medications and surgical techniques that may inhibit this process.

PMID- 19763696
TI  - Subacromial injection improves deltoid firing in subjects with large rotator cuff
      tears.
AB  - Previous studies demonstrate that scapulohumeral mechanics improve after
      subacromial injection. However, it is unclear how injection affects muscle
      firing. Forty-one subjects with two-tendon rotator cuff tears and 23 volunteer
      subjects with normal rotator cuffs documented by ultrasonography were examined.
      Electromyographic activity from 12 muscles was collected during ten functional
      tasks. Nine symptomatic subjects with rotator cuff tears underwent subacromial
      injection of anesthetic and underwent repeat electromyographic examination.
      Subjects with rotator cuff tears demonstrate global electromyographic differences
      when compared to normal controls. Asymptomatic subjects with rotator cuff tears
      had significantly increased anterior deltoid firing when compared to symptomatic
      counterparts during forward shoulder elevation. After subacromial injection,
      symptomatic subjects demonstrate increased anterior deltoid firing. Previous in
      vitro and in vivo studies have suggested that pain leads to deltoid inhibition
      and that subacromial injection leads to improved deltoid firing and,
      subsequently, improved shoulder function. This study provides direct evidence
      that subacromial injection improves deltoid firing in symptomatic subjects with
      rotator cuff tears. These findings reinforce the concept that deltoid inhibition
      resulting from pain is an important component of the motor disability associated
      with rotator cuff tears.

PMID- 19763697
TI  - Defining medical basic science: general internists' special role in the
      reformation of medical school education.

PMID- 19763698
TI  - Provider recommendations for colorectal cancer screening in elderly veterans.
AB  - BACKGROUND: Decisions regarding colorectal cancer (CRC) screening in the elderly
      depend on providers' assessment of likelihood of benefit partly based on patient
      comorbidity and past screening history. We aimed to describe providers'
      experiences and practice patterns regarding screening for CRC in elderly patients
      in the VA system. METHODS AND PARTICIPANTS: A survey was sent to VA primary care
      providers who had previously participated in the CanCORS-sponsored Share Thoughts
      on Care study and at a VA medical center. The surveys consisted of clinical
      vignettes that varied by patient age (75, 80, or 85 years), comorbidity, and past
      CRC screening history. MAIN RESULTS: Completed questionnaires were received from
      183 of 351 providers (52%). Ninety-five percent of providers would recommend
      screening for a healthy 75 year old compared to 66% and 39% for a healthy 80 and
      85 year old, respectively (p-values < 0.0001). Providers were more likely to
      recommend screening for a 75 year old with moderate CHF versus severe CHF [61%
      versus 15%, OR 9.0 (95% CI 5.8-14.0), p < 0.0001] and more likely to recommend
      screening for an 80 year old with prior colonoscopy within the preceding 10
      years, versus 5 years [42% versus 23%, OR 2.6 (95% CI 1.9-3.5), p < 0.0001]. A
      substantial minority of respondents (range 15-21%) reported they would screen a
      75 year old with an active malignancy, severe CHF, or severe COPD. Provider
      demographic characteristics were not significantly associated with the
      probability of a screening recommendation. CONCLUSIONS: VA providers incorporate
      patient age, comorbidity, and past CRC screening history into CRC screening
      recommendations for elderly veterans; however, substantial proportions of these
      recommendations are inappropriate.

PMID- 19763699
TI  - Behind closed doors: physician-patient discussions about colorectal cancer
      screening.
AB  - BACKGROUND: Despite the availability of multiple effective screening tests for
      colorectal cancer, screening rates remain suboptimal. The literature documents
      patient preferences for different test types and recommends a shared decision
      making approach for physician-patient colorectal cancer screening (CRCS)
      discussions, but it is unknown whether such communication about CRCS preferences
      and options actually occurs in busy primary-care settings. OBJECTIVE: Describe
      physician-patient CRCS discussions during a wellness visit. DESIGN: Cross
      sectional; patients audio-recorded with physicians. PARTICIPANTS: A subset of
      patients (N = 64) participating in a behavioral intervention trial designed to
      increase CRCS who completed a wellness visit during the trial with a
      participating physician (N = 8). APPROACH: Transcripts were analyzed using
      qualitative methods. RESULTS: Physicians in this sample consistently recommended
      CRCS, but focused on colonoscopy. Physicians did not offer a fecal occult blood
      test alone as a screening choice, which may have created missed opportunities for
      some patients to get screened. In this single visit, physicians' communication
      processes generally precluded discussion of patients' test preferences and did
      not facilitate shared decision-making. Patients' questions indicated their
      interest in different CRCS test types and appeared to elicit more information
      from physicians. Some patients remained resistant to CRCS after discussing it
      with a physician. CONCLUSION: If a preference for colonoscopy is widespread among
      primary-care physicians, the implications for intervention are either to prepare
      patients for this preference or to train physicians to offer options when
      recommending screening to patients.

PMID- 19763700
TI  - Physician respect for patients with obesity.
AB  - INTRODUCTION: Obesity stigma is common in our society, and a general stigma
      towards obesity has also been documented in physicians. We hypothesized that
      physician respect for patients would be lower in patients with higher body mass
      index (BMI). METHODS: We analyzed data from the baseline visit of 40 physicians
      and 238 patients enrolled in a randomized controlled trial of patient-physician
      communication. The independent variable was BMI, and the outcome was physician
      respect for the patient. We performed Poisson regression analyses with robust
      variance estimates, accounting for clustering of patients within physicians, to
      examine the association between BMI and physician ratings of respect for
      particular patients. RESULTS: The mean (SD) BMI of the patients was 32.9(8.1)
      kg/m(2). Physicians had low respect for 39% of the participants. Higher BMI was
      significantly and negatively associated with respect [prevalence ratio (PrR)
      0.83, 95% CI: 0.73-0.95; p = 0.006; per 10 kg/m(2) increase in BMI]. BMI remained
      significantly associated with respect after adjustment for patient age and gender
      (PrR 0.86, 95%CI: 0.74-1.00; p = 0.049). CONCLUSION: We found that higher patient
      BMI was associated with lower physician respect. Further research is needed to
      understand if lower physician respect for patients with higher BMI adversely
      affects the quality of care.

PMID- 19763701
TI  - Clinical significance of the upregulated osteopontin mRNA expression in human
      colorectal cancer.
AB  - OBJECTIVE: Osteopontin (OPN) is a phosphorylated glycoprotein which is associated
      with tumor progression, development, and metastasis. Recently, it has been
      reported that OPN is highly upregulated in a variety of human malignancies. The
      aim of this study is to investigate the clinical significance of OPN mRNA
      expression in colorectal cancer (CRC). MATERIAL AND METHODS: Conventional reverse
      transcription polymerase chain reaction (RT-PCR) and Western blot assays were
      performed to detect the expression of OPN mRNA and protein in human CRC cell
      lines and normal cell line. Real-time quantitative RT-PCR assay was performed to
      analyze the expression of OPN mRNA in 82 CRC tissue samples and corresponding non
      tumor tissues. Immunohistochemistry was also performed to detect the expression
      of OPN protein in above tissues. Finally, the correlation between the status of
      OPN mRNA expression and clinicopathological factors and clinical outcome was
      evaluated. RESULTS: Compared with normal human intestinal epithelial cell line,
      human CRC cell lines showed high level of OPN gene expression at both
      transcriptional and translational levels. Moreover, the results of real-time
      quantitative RT-PCR and immunohistochemistry showed that the expression levels of
      OPN mRNA and protein in tumor tissues were significantly higher than those in the
      corresponding non-tumor tissues (P < 0.001). The expression level of OPN mRNA was
      significantly correlated with lymph node metastasis, lymphatic or venous
      invasion, and TNM stage (P = 0.0033, 0.0061, 0.0008, and 0.0012, respectively).
      Moreover, we also observed that the disease-free and overall survival rates in
      patients with high OPN mRNA expression were significantly shorter than those in
      patients with low OPN mRNA expression (P = 0.0047 and 0.0125). Additionally, the
      status of OPN mRNA expression was an independent prognostic factor for the
      prognosis of CRC patients (P = 0.008; RR, 2.775; 95% confidence interval, 2.334
      3.811). CONCLUSION: OPN might play an important role in CRC progression and the
      status of OPN mRNA expression could be a novel prognostic molecular marker for
      CRC patients.

PMID- 19763702
TI  - Downregulation of adiponectin/AdipoR2 is associated with steatohepatitis in obese
      mice.
AB  - BACKGROUND: Recent evidence suggests that obesity is associated with hypo
      adiponectinmia and chronic inflammation. Adiponectin regulates fat storage,
      energy expenditure, and inflammation. We propose that high fat diet induces
      steatohepatitis, reduces serum adiponectin, and liver adiponectin receptors.
      METHODS: A 4-week-old C57BL male mice were fed high fat diet (n = 8) or regular
      chow (control; n = 6) for 7 weeks. Body weight, liver weight, and serum
      adiponectin were measured. Liver sections were stained with hematoxylin and eosin
      and oil red for fat content. Liver homogenates were used for protein
      (immunoblotting) and mRNA (reverse transcription PCR) of Toll-like receptor 4
      (TLR4), tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-6, sterol
      regulatory element-binding proteins (SREBP)-1c, and adiponectin receptors
      (AdipoR1/AdipoR2) in addition to nuclear phorsphorylated p65NF-kappaB. Gels were
      quantified using densitometry; t test was used, and p < 0.05 was significant.
      RESULTS: High fat diet increased body (50%) and liver weight (33%), as well as
      hepatocyte fat content and ballooning. Mice fed high fat diet exhibited reduced
      serum adiponectin and liver AdipoR2. High fat diet increased hepatic levels of
      SREBP-1c, TLR4, TNF-alpha, and IL-6 protein and mRNA and increased activation of
      p65NF-kappaB. CONCLUSIONS: Diet-induced liver steatosis is associated with
      increased lipogensis, upregulation of pro-inflammatory cytokines, and
      transcription factors as well as downregulation of AdipoR2. Reduction in serum
      adiponectin suggests that adiponectin signaling may be the crosslink between high
      fat diet, hepatic inflammation, and nonalcoholic fatty liver disease.

PMID- 19763703
TI  - High-resolution esophageal manometry: using technical advances for clinical
      advantages.
AB  - BACKGROUND: High-resolution manometry (HRM) is a new technique to investigate the
      motor function of the esophagus. It differs from conventional manometry in
      recording pressures by solid state microtransducers at 12 points around the
      circumference at every centimeter of esophageal length, and displaying the data
      in pseudo-three-dimensional format using a topographic plot, where esophageal
      pressures within a given range are represented by different colors. RATIONALE:
      The large amount of data and the capacity to analyze and display it intuitively
      has afforded many new insights into esophageal dysfunction. Among these insights
      are the ability to distinguish three different subtypes of achalasia and predict
      their response to therapy, better understanding of the relationship between the
      lower esophageal sphincter (LES) and the crural diaphragm, the development of
      novel quantitative parameters to understand the nature of the dysfunction in non
      specific esophageal motor disorders, and the elucidation of a newly described
      motility disorder characterized by failure of peristalsis at the transitional
      zone between the upper skeletal muscle and the more distal smooth muscle portion
      of the esophagus. It is also ideally suited to analysis of the effect of
      prokinetic medications. The method is quicker and less uncomfortable for patients
      and the analysis is visually appealing and intuitively comprehensible.
      CONCLUSION: Despite these potential advantages, there are currently no data to
      demonstrate a clinical advantage in treatment. The results of such studies will
      be crucial to the acceptance of this novel technology.

PMID- 19763705
TI  - Usefulness of continuous glucose monitoring for the diagnosis of hypoglycemia
      after a gastric bypass in a patient previously treated for type 2 diabetes.
AB  - Hypoglycemia is rare after a gastric bypass and can be taken for a dumping
      syndrome. There is no report in the literature of the contribution of continuous
      glucose monitoring to the diagnosis of hypoglycemia in these circumstances. The
      present case report shows that continuous glucose monitoring can be a useful tool
      for the diagnosis and the management of such episodes. Continuous glucose
      monitoring revealed hypoglycemic episodes in free living circumstances that were
      not present during 72-h fasting. These episodes followed wide hyperglycemic
      swings. No such episode resumed over 8 months after specific dietary advices and
      treatment by 50 mg TID of acarbose. Because hypoglycemia can be difficult to
      diagnose from dumping syndrome, continuous glucose monitoring is a very useful
      tool revealing the episodes in free living circumstances and can be used to
      monitor the treatment success.

PMID- 19763706
TI  - Surgeon-performed fluoroscopy conducted simultaneously during all laparoscopic
      adjustable gastric band adjustments results in significant alterations in
      clinical decisions.
AB  - BACKGROUND: Little data exists regarding filling regimens for laparoscopic
      adjustable gastric bands (LAGB). In addition to patient symptoms and weight
      changes, we have instituted surgeon-performed, real-time fluoroscopic evaluation
      in our clinical decision making during all band adjustments. OBJECTIVE: Our
      hypothesis is that surgeon-performed, real-time contrast fluoroscopy conducted
      routinely during all LAGB adjustment results in significant deviations in
      clinical care. SETTING: The study is set at the Academic Referral Center, United
      States METHODS: Fifty-two consecutive patients who underwent LAGB and presented
      for adjustment were given a questionnaire evaluating obstructive symptoms. The
      patient's weight loss history was also reviewed. Each patient underwent real-time
      fluoroscopy performed by the surgeon during adjustment. Data were recorded and
      compared to final decision to fill, make no adjustment, or remove fluid. RESULTS:
      Patients were, on average, at post-operative visit 5. Sixty-three percent of
      patients received a fill, 31% had no change, and 6% had fluid removed. On the
      questionnaire, 15% of patients noted reflux, 10% had dysphagia, and 8% had
      regurgitation. Eighty percent of patients requested a fill. Thirty-one percent
      had an abnormality noted on fluoroscopy. Fifteen percent of patients demonstrated
      esophageal dilation, 15% had a delay of greater than 5 s, 19% had reflux of
      contrast. Three patients had band displacements on imaging. Additionally, six
      patients (12%) were not filled based on fluoroscopic findings alone, not
      predicted by either the survey or historical weight loss. CONCLUSION: Surgeon
      performed, real-time, fluoroscopy during LAGB adjustment results in significant
      changes in clinical care that are not predicted by history and weight loss alone.
      Routine fluoroscopic imaging altered the course of management in 12% of patients
      and identified three asymptomatic displaced bands.

PMID- 19763707
TI  - Pathophysiology of laparoscopic adjustable gastric bands: analysis and
      classification using high-resolution video manometry and a stress barium
      protocol.
AB  - BACKGROUND: Symmetrical pouch dilatation has become the most common problem
      following laparoscopic adjustable gastric banding (LAGB). Although, in a
      significant number of symptomatic patients, no explanation for the underlying
      problem is identified with a contrast swallow. There is a need for a better
      understanding of the pathophysiology of LAGBs and more sensitive diagnostic
      tests. METHODS: LAGB patients with adverse symptoms or poor weight loss
      (symptomatic patients), in whom a contrast swallow had not shown an abnormality,
      underwent high-resolution video manometry. This incorporated a semi-solid, stress
      barium, swallow protocol. Outcomes were categorized based on anatomical
      appearance, transit through the LAGB, and esophageal motility. Cohorts of
      successful (>50% excess weight loss with no adverse symptoms) and pre-operative
      patients were used as controls. RESULTS: One hundred twenty-three symptomatic
      patients participated along with 30 successful and 56 pre-operative patients.
      Five pathophysiological patterns were defined: transhiatal enlargement (n = 40),
      sub-diaphragmatic enlargement (n = 39), no abnormality (n = 30), aperistaltic
      esophagus (n = 7), and intermittent gastric prolapse (n = 3). Esophageal motility
      disorders were more common in symptomatic and pre-operative patients than in
      successful patients (p = 0.01). Differences between successful and symptomatic
      patients were identified in terms of the length of the high-pressure zone above
      the LAGB (p < 0.005), peristaltic velocity (p < 0.005), frequency of previous
      surgery(p = 0.01), and lower esophageal sphincter tone (p = 0.05). CONCLUSIONS:
      Video manometry identified abnormalities in three quarters of symptomatic
      patients where conventional contrast swallow had not been diagnostic. Five
      primary patterns of pathophysiology were defined. These were used to develop a
      seven category, clinical, classification system based on the anatomical
      appearance at stress barium. This system stratifies the spectrum of symmetrical
      pouch dilatation and can be used to logically guide treatment.

PMID- 19763708
TI  - Results and complications after Swedish adjustable gastric banding-10 years
      experience.
AB  - BACKGROUND: Bariatric surgery is currently the only effective treatment for
      morbid obesity. The main advantage of laparoscopic adjustable gastric banding is
      that this operation is minimally invasive to the stomach and adjustable to the
      patient's needs. Few long-term studies on Swedish adjustable gastric banding
      (SAGB) have been published. We here report our 10-year experience with 785 SAGB
      procedures. METHODS: Between January 1996 and January 2006, 785 consecutive
      patients (81% women, 19% men) underwent laparoscopic SAGB. All data (demographic
      and morphologic, operative, and annual follow-up data) were prospectively
      collected in a computerized data bank. The postoperative follow-up program was
      performed largely by residents while 30 different surgeons performed the
      operation. RESULTS: Follow up data were available for 733 patients (98.3%); 52
      patients (6.6%) were lost to follow-up. The median follow-up was 3.0 years
      (range, 1-10 years). The median total weight loss was 26 kg after 1 year and 40.5
      kg after 8 years with a median EWL of 65.5% after 8 years. The median BMI
      decreased from 42.9 to 28.3 kg/m2. A total number of 688 complications occurred
      in 396 patients (50.4%). The most common complications were esophagitis (28.8%),
      pouch dilation (15.3%), esophageal dilation (12.5%), port problems (11%), band
      migration (6.5%), and band leakage (6.4%). Overall, 251 reoperations (32%) were
      performed. There was no mortality. CONCLUSIONS: From our 10-year experience, we
      can state that SAGB is an effective bariatric procedure for achieving weight
      loss. Because of the high complication and reoperation rate, it is necessary to
      select patients according to specific criteria for gastric banding.

PMID- 19763709
TI  - Prompt reduction in use of medications for comorbid conditions after bariatric
      surgery.
AB  - BACKGROUND: Bariatric surgery leads to weight loss, but it is unclear whether
      surgery reduces conditions associated with obesity. We explored this by assessing
      the change in use of medications to treat diabetes mellitus, hypertension, and
      hyperlipidemia in the year following surgery. METHODS: This is a cohort study
      using administrative data from 2002 to 2005 from seven Blue Cross/Blue Shield
      Plans. We compared the mean number of medications at the time of surgery and in
      the subsequent year. Medication usage by surgical patients was also compared to
      usage by matched enrollees without surgery but with a propensity score suggesting
      obesity. With Poisson and logistic regression, we tested for statistical
      differences in usage, accounting for repeated measures and controlling for age,
      sex, and diabetes. We also evaluated medications expected to be less influenced
      by surgery (antidepressants, thyroid replacement, and antihistamines). RESULTS:
      Our cohort included 6,235 enrollees with bariatric surgery. Their mean age was 44
      years with 82% women; 34% had diabetes. Medication use declined significantly by
      3 months. By 12 months after surgery, medication use for diabetes, hypertension,
      and hyperlipidemia had declined by 76%, 51%, and 59%, respectively. In contrast,
      thyroid hormone, antihistamine, and antidepressant use decreased by only 6%, 15%,
      and 9%, respectively. Enrollees without surgery had a modest increase in
      medications for diabetes, hypertension, and hyperlipidemia of 4%, 8%, and 20%,
      respectively. CONCLUSIONS: Medication use for three serious obesity-associated
      conditions decreased promptly following surgery. The clinical and economic
      benefits of reduced medication requirements should be considered when making
      decisions about the effects of bariatric surgery.

PMID- 19763710
TI  - Voice feature characteristic in morbid obese population.
AB  - BACKGROUND: Morbid obesity is highly prevalent in the Western World, and its
      consequences present a real public health challenge. Voice alterations can
      represent one of these consequences and represent an opportunity for interference
      with therapeutic methods. This particularly features of the individual's voice
      was the goal of the present study. METHODS: A group of 45 adult volunteers of
      both sexes with a BMI greater than 35 Kg/m(2) was selected among patients of the
      Obesity Ambulatory of the Digestive Surgery Division. The control group consisted
      of volunteers matched by sex, age (+/-1 year), and smoking habits, but with a BMI
      below 30 Kg/m(2). All subjects were submitted to laryngoscopic examination, audio
      perceptive analysis, and voice acoustics determination. Examinations were always
      performed by the same doctor, and diagnoses were provided by two different
      physician specialists in laryngology and voice. RESULTS: Obese individuals
      exhibit the following modifications in voice feature: hoarseness, murmuring,
      vocal instability, altered jitter and shimmer, and reduced maximum phonation
      times as well the presence of voice strangulation at the end of emission.
      CONCLUSION: The voices of individuals with morbid obesity are different of the
      voice of nonobese people and demonstrate significant changes in vocal
      characteristics.

PMID- 19763711
TI  - Subcutaneous and visceral adipose tissue FTO gene expression and adiposity,
      insulin action, glucose metabolism, and inflammatory adipokines in type 2
      diabetes mellitus and in health.
AB  - BACKGROUND: FTO gene variants are linked to obesity. We tested for site-specific
      differences in FTO gene expression in subcutaneous and visceral adipose tissue
      (SAT and VAT, respectively) from individuals with and without type 2 diabetes
      mellitus (T2D) and the relationships between fasting glucose, in vivo insulin
      action, and measures of adiposity with FTO gene expression in adipose tissue.
      METHODS: Paired subcutaneous and visceral fat were excised at elective surgery in
      n = 16 subjects (six with T2D, age-matched). Metabolic parameters were measured
      in fasted state; body composition by dual-energy X-ray absorptiometry; and
      insulin action by hyperinsulinemic euglycemic clamp. Adipose tissue mRNA gene
      expression was determined by quantitative RT-PCR. RESULTS: Subjects with T2D had
      SAT and VAT FTO mRNA expression similar to controls. There was no depot
      specificity between SAT and VAT FTO mRNA expression. Insulin action did not
      relate to SAT or VAT FTO mRNA expression. SAT FTO mRNA expression was related to
      fasting glucose and waist circumference only. SAT and VAT FTO mRNA expression was
      not related to direct measures of total or central abdominal adiposity. SAT FTO
      mRNA expression was related to SAT tumor necrosis factor-alpha and nuclear factor
      kappaB mRNA expression. CONCLUSIONS: FTO gene expression is not increased in SAT
      and VAT in T2D and does not relate to insulin action. The links between FTO and
      metabolic complications of diabetes require further elucidation.

PMID- 19763713
TI  - Combined hepatocellular and cholangiocarcinoma with sarcomatoid transformation:
      radiologic-pathologic correlation of a case.
AB  - A 71-year-old man presented to our hospital with 3-week history of fever in the
      background of loss of both weight and appetite over the past 3 months. He was
      found to have a large 10-cm mass in the right lobe of the liver on a triple-phase
      computed tomographic scan. The tumor showed a distinct fatty component, with
      areas of arterial enhancement and venous washout suggestive of hepatocellular
      carcinoma (HCC), another component showing progressive and late enhancement
      suggestive of cholangiocarcinoma (CC), and a third component showing persistent
      hypoenhancement relative to the liver parenchyma. He underwent surgical
      resection. This was histopathologically a biphasic tumor composed of areas
      showing hepatocytic differentiation, in contiguity with areas showing
      infiltrative glands set within fibrous stroma in keeping with combined
      hepatocellular and cholangiocarcinoma (cHCC-CC). A third component of pleomorphic
      spindle and epithelioid appearance in keeping with sarcomatous transformation was
      also found intimately related to the CC component. The patient developed
      extensive thoracic and abdominal metastases 2 months after surgery and died
      shortly after.

PMID- 19763714
TI  - The role of quantitative hepatitis B serology in the natural history and
      management of chronic hepatitis B.
AB  - Chronic hepatitis B (CHB) remains a serious clinical problem worldwide. Advances
      in molecular technology have enabled the development of sensitive assays for the
      detection and quantification of hepatitis B virus (HBV) nucleic acid and
      demonstrated a positive correlation between serum HBV DNA levels and disease
      progression. Assessment of specific serologic and virologic factors also plays a
      pivotal role in the diagnosis and effective management of individuals with CHB.
      Recent development of quantitative assays for intrahepatic HBV replicative
      intermediates, as well as hepatitis B e antigen and hepatitis B surface antigen,
      has spurred investigation into the relationship between these factors and
      response to antiviral therapy and disease progression. Recent findings from
      preclinical and clinical investigations indicate that these factors may have
      promise in identifying patients likely to respond to treatment. Additional work
      is needed to standardize and validate these assays before they can be considered
      to be of true diagnostic value. Further evaluation is needed to decide which will
      have the greatest clinical applicability.

PMID- 19763715
TI  - Healed cuff repairs impart normal shoulder scores in those 65 years of age and
      older.
AB  - BACKGROUND: It is unclear whether repaired rotator cuffs heal in older patients
      and whether the function in those shoulders compares with those of similarly aged
      patients with untreated tears. QUESTIONS/PURPOSE: We questioned whether, in
      patients 65 years of age and older, shoulders with rotator cuff repairs that
      remained intact would have Simple Shoulder Test (SST) scores and Constant scores
      similar to those of untreated individuals with intact rotator cuffs. METHODS: We
      retrospectively reviewed 39 patients (42 shoulders) 65 years of age and older in
      whom 42 full-thickness rotator cuff tears were repaired with a mini open
      technique. All patients completed SST and Constant scores 12 to 60 months
      postoperatively; all patients also had ultrasound at those times to assess the
      status of the repair. These findings were compared with 200 untreated similarly
      aged shoulders assessed in the same fashion. RESULTS: Shoulders with healed
      repairs (33 of 42) had similar mean SST scores and Constant scores to those in
      untreated shoulders with intact rotator cuffs. Those with healed repairs also had
      higher SST and Constant scores than those with unhealed repairs. Finally,
      shoulders with healed repairs had higher SST and Constant scores than those with
      untreated tears. CONCLUSIONS: When rotator cuffs healed the function was
      comparable to that of similarly-aged patients without tears and better than that
      of patients with untreated tears. LEVEL OF EVIDENCE: Level III, therapeutic
      study. See Guidelines for Authors for a complete description of levels of
      evidence.

PMID- 19763716
TI  - Fear in arthroplasty surgery: the role of race.
AB  - Understanding the difference in perceived functional outcomes between whites and
      blacks and the influence of anxiety and pain on functional outcomes after joint
      arthroplasty may help surgeons develop ways to eliminate the racial and ethnic
      disparities in outcome. We determined the difference in functional outcomes
      between whites and blacks and assessed the influence of fear and anxiety in total
      joint arthroplasty outcomes in 331 patients undergoing primary hip and knee
      arthroplasty. WOMAC, Quality of Well Being, SF-36, and Pain and Anxiety Symptoms
      Scale (PASS) were administered pre- and postoperatively (average 5-year
      followup). For the SF-36 General Health Score, blacks reported having worse
      perceived general health than whites before surgery. Regardless of time, blacks
      scored worse than whites for all measures except for the SF-36 physical function
      and general health scores. Blacks had a greater fear score (ie, that associated
      with the procedure) and total PASS score. For both races, there was a low
      association between the fear dimensions and dependent measures before and after
      surgery. Black patients undergoing hip and knee arthroplasty had lower scores
      than whites in most outcome measures regardless of time of assessment. We found
      higher fear levels before joint arthroplasty in blacks compared with whites.
      After surgery, blacks had much higher associations of the fear subscale,
      cognitive subscale, and total PASS score with the WOMAC physical function, pain,
      and total scores. LEVEL OF EVIDENCE: Level II, prospective controlled cohort
      study. See Guidelines for Authors for a complete description of levels of
      evidence.

PMID- 19763717
TI  - Fine needle aspiration for clinical triage of extremity soft tissue masses.
AB  - BACKGROUND: Fine needle aspiration cytology (FNAC) is a rapid and low-morbid
      alternative to open biopsy or needle core biopsy for soft tissue masses. Numerous
      reports describe its use with metastatic or recurrent lesions, but FNAC is less
      accepted for primary lesions. QUESTIONS/PURPOSES: We wished (1) to estimate the
      sensitivity, specificity, and positive and negative predictive values of FNAC for
      diagnosing malignancy; (2) to estimate the accuracy of subtyping and grading.
      METHODS: We retrospectively examined the diagnostic accuracy and clinical
      effectiveness of office-based FNAC performed by a trained pathologist on 213
      females and 219 males (mean age, 51.8 years) who presented with a palpable soft
      tissue mass to one musculoskeletal oncology clinic between 2002 and 2008.
      RESULTS: The FNAC was reported as benign in 62.0%, indeterminate in 8.1%, and
      malignant in 29.9%. A second technique, such as needle core biopsy or open
      biopsy, was performed for 24.8% of lesions before a definitive treatment plan was
      rendered. Final tissue confirmation by open biopsy or resection was available for
      52.2% of benign FNAC and 78.3% of malignant FNAC. Sensitivity, specificity, and
      positive and negative predictive values for detecting malignancy with either
      histopathologic confirmation or clinical followup were 89.2%, 89.8%, 96.1%, and
      98.1%. There were seven sampling and nine interpretation FNAC errors in
      determining the nature of the lesion. Subtyping and grading for malignant lesions
      were 77.2% and 95.2% accurate, respectively. CONCLUSIONS: FNAC is effective for
      initial triage and treatment selection at tertiary referral centers with close
      collaboration among the surgeon, pathologist, and radiologist. LEVEL OF EVIDENCE:
      Level II, diagnostic study. See the Guidelines for Authors for a complete
      description of levels of evidence.

PMID- 19763718
TI  - The effect of soaking allograft in bisphosphonate: a pilot dose-response study.
AB  - BACKGROUND: Long-term survival of uncemented total joint replacements relies on
      osseointegration. With reduced bone stock impacted morselized allograft enhances
      early implant fixation but is subject to resorption. PURPOSE: We therefore asked
      whether soaking morselized allograft in different concentrations of
      bisphosphonate before impaction would enhance fixation. METHODS: In each of 10
      dogs, we implanted four unloaded titanium implants surrounded by a 2.5-mm gap
      into the proximal humerus, two implants in each humerus. The gap was filled with
      impacted morselized allograft soaked in saline or a low-, middle-, or high-dose
      bisphosphonate solution (0.005, 0.05, or 0.5 mg zoledronate/mL). At 4 weeks, the
      implants were evaluated by histomorphometric analysis and mechanical pushout
      test. RESULTS: The low dose of zoledronate increased new bone formation in the
      allograft but the high dose decreased new bone formation. The high dose of
      zoledronate resulted in the greatest inhibition of allograft resorption, whereas
      the low dose of zoledronate resulted in the lowest inhibition of allograft
      resorption. Implants surrounded allograft soaked in the low dose of zoledronate
      or saline had better fixation for all three mechanical parameters compared with
      implants surrounded by allograft soaked in the middle or high dose of
      zoledronate. CONCLUSIONS: These data suggest bisphosphonate may enhance
      osseointegration of allografted implants and emphasize the need for preclinical
      testing of antiresorptive therapies.

PMID- 19763719
TI  - Osseous remodeling after femoral head-neck junction osteochondroplasty.
AB  - Femoral head-neck junction osteochondroplasty is commonly used to treat
      femoroacetabular impingement, yet remodeling of the osteochondroplasty site is
      not well described. We therefore describe bony remodeling at the
      osteochondroplasty site and analyze clinical outcomes and complications
      associated with femoral osteochondroplasty. We retrospectively reviewed 135
      patients (150 hips) who underwent femoral head-neck osteochondroplasty combined
      with hip arthroscopy, surgical hip dislocation, periacetabular osteotomy, or
      proximal femoral osteotomy. The minimum clinical followup was 10 months (mean,
      22.3 months; range, 10-65 months). We assessed the femoral-head neck offset, head
      neck offset ratio, alpha angle, and cortical remodeling. We used the Harris hip
      score to determine hip function. We observed an increase in the head-neck offset,
      offset ratio, and decrease in the alpha angle postoperatively and at latest
      followup. Ninety-eight of 113 (87%) hips had partial or complete
      recorticalization at the osteochondroplasty site. The mean Harris hip score
      improved from 64 to 85. We excised heterotopic bone in one hip. There were no
      femoral neck fractures. The deformity correction achieved with femoral head-neck
      osteochondroplasty is maintained and recorticalization occurs in the majority of
      cases during the first two years. LEVEL OF EVIDENCE: Level IV, therapeutic study.
      See Guidelines for Authors for a complete description of levels of evidence.

PMID- 19763720
TI  - The classic: The iliac apophysis: an invaluable sign in the management of
      scoliosis. 1958.

PMID- 19763721
TI  - The natural progression of shoulder osteonecrosis related to corticosteroid
      treatment.
AB  - BACKGROUND: Little is known about the rate and factors of progression of shoulder
      osteonecrosis (ON) related to corticosteroids. PURPOSE: We retrospectively
      evaluated 125 patients (215 shoulders) with humeral head ON diagnosed by MRI to
      determine the delay between corticosteroid treatment and the different stages and
      factors influencing the progression of the disease. METHODS: Seventy-four of the
      shoulders had asymptomatic Stage I ON, 58 had asymptomatic Stage II ON, 46 had
      symptomatic Stage I ON, and 37 had symptomatic Stage II ON. The minimum followup
      was 10 years (average, 14 years; range, 10-20 years). The delay between the
      beginning of the corticosteroid treatment and the diagnosis of ON of the humeral
      head averaged 15 months (range, 6-24 months). RESULTS: We observed partial or
      total regression on MRI only in patients with asymptomatic Stage I ON. At last
      followup, pain had developed in 98 (74%) and collapse had occurred in 71 (54%) of
      the 132 previously asymptomatic shoulders. Of the 83 symptomatic shoulders, 68
      (82%) had collapsed at the final followup. The time between diagnosis and
      collapse averaged 10 years for patients with symptomatic Stage I ON and 3 years
      for patients with symptomatic Stage II ON. CONCLUSIONS: Stage at initial visit,
      occurrence of pain, and continuation of peak doses of corticosteroids predicted
      progression of disease in asymptomatic shoulders, whereas in the symptomatic
      shoulders, extent and location of the lesion were the main risk factors for
      progression. LEVEL OF EVIDENCE: Level II, prognostic study. See Guidelines for
      Authors for a complete description of levels.

PMID- 19763722
TI  - Endoscopic gastrocnemius recession for treating equinus in pediatric patients.
AB  - Gastrocnemius recessions have been performed as open or endoscopic procedures.
      Most of the literature describes the outcomes of these procedures in children
      with specific neurologic limitations. We report an alternative approach to
      endoscopic gastrocnemius recessions in neurologically healthy pediatric and
      adolescent patients whose gastrocnemius equinus could not be corrected
      nonoperatively. We prospectively followed 23 patients (16 boys, seven girls) who
      underwent 40 procedures for equinus deformity (n = 22) or osteoarthritis (n = 1).
      All patients had been directly referred for surgical treatment because all
      previous nonoperative treatments (stretching, night splints, orthotics,
      nonsteroidal anti-inflammatory drugs, and physical therapy) had failed. The
      indications for surgery were patients age 18 years or younger experiencing
      symptomatic equinus unresponsive to nonoperative care. Pre- and postoperative
      ankle dorsiflexion were measured. The minimum followup for study inclusion was 1
      year (mean, 2.9 years; range, 2-5.1 years). For every patient, dorsiflexion range
      of motion improved (mean, 15 degrees ; standard deviation, 4 degrees ). No
      patient had diminished nerve sensation postoperatively. This technique can be
      used to correct gastrocnemius equinus in otherwise healthy children who have not
      benefited from prior nonsurgical treatment. LEVEL OF EVIDENCE: Level IV,
      therapeutic study. See Guidelines for Authors for a complete description of
      levels of evidence.

PMID- 19763723
TI  - Muscone protects vertebral end-plate degeneration by antiinflammatory property.
AB  - Most chronic neck pain is the result of degeneration of the cervical spine. IL
      1beta may play an important role in intervertebral disc degeneration. This being
      the case, inhibiting IL-1beta could provide a therapeutic approach for reducing
      or preventing disc degeneration. Muscone reportedly relieves pain and suppresses
      inflammation. Therefore, we asked whether muscone, a potent antiinflammatory
      agent, could reduce proinflammatory cytokines in vitro (end-plate cartilage
      cultures) and end-plate degeneration in vivo (a rat model that induces
      intervertebral disc degeneration). In vitro, muscone reversed IL-1beta-induced
      upregulation of IL-1beta, tumor necrosis factor alpha, cyclooxygenase 2,
      inducible nitric oxide synthase, matrix metalloproteinase 13, aggrecanase 2, and
      nitric oxide and downregulation of Col2alpha1 and aggrecan. Pretreatment with
      muscone (6.25, 12.5, 25 mumol/L) inhibited the IL-1beta-induced phosphorylation
      of extracellular signal-regulated kinases 1/2 and c-Jun N-terminal kinase in a
      dose-dependent manner. In vivo, muscone inhibited the expression of prostaglandin
      E2, 6-keto-prostaglandin F1alpha, IL-1beta, and tumor necrosis factor alpha and
      recovered the structural distortion of the degenerative disc. Our findings
      suggest muscone is a promising agent for treating intervertebral disc
      degeneration through its antiinflammatory effects.

PMID- 19763724
TI  - Differential expression of vascular endothelial growth factor in glucocorticoid
      related osteonecrosis of the femoral head.
AB  - VEGF plays a role in bone remodeling. Ingrowth of reparative arterioles can be
      observed in late-stage osteonecrosis. To explore the reparative processes, we
      quantified the most important angiogenesis factor (VEGF) in different zones of
      late-stage glucocorticoid-induced osteonecrosis. We treated primary
      nonosteonecrosis osteoblasts with glucocorticoids in vitro as a model for the
      bone cells in early-stage steroid-related osteonecrosis. We obtained six late
      stage (ARCO Stage IV) osteonecrosis femoral heads and six osteoarthritic femoral
      heads during THA. The expression of vascular endothelial growth factor was
      analyzed by reverse-transcription PCR, ELISA, or immunohistochemistry.
      Osteoblasts from the reactive interface (penumbra) of osteonecrosis femoral heads
      exhibited increased immunoreactivity to VEGF compared to those from the
      periphery. ELISA confirmed VEGF upregulation in the penumbra from osteonecrosis
      femoral heads. Primary osteoblasts derived from osteoarthritic femoral heads
      exhibited downregulation of VEGF after 24 hours of coincubation with
      glucocorticoids. The increase in VEGF in the reactive interface (penumbra) of
      osteonecrosis in late-stage femoral head may reflect a secondary phenomenon. The
      observed high amount of VEGF in later-stage osteonecrosis might stimulate the
      ingrowth of reparative arterioles into the femoral head.

PMID- 19763725
TI  - Is there faster recovery with an anterior or anterolateral THA? A pilot study.
AB  - Surgical technique is an important factor affecting recovery of hip function
      after total hip arthroplasty (THA). We therefore asked whether short-term
      recovery of hip strength and motion would differ between the anterior and
      anterolateral THA approaches. We presumed that although both approaches would
      improve hip function by 16 weeks postsurgery when compared with presurgery, a
      slower recovery would be demonstrated by the anterolateral group at 6 weeks when
      compared with the anterior group as a result of division and reattachment of the
      abductor muscles. We observed hip kinematics and kinetics during walking and
      isometric hip abductor strength for the involved limb. Hip abductor strength of
      all patients was lower than controls at all three testing times. Compared with
      presurgery, all patients demonstrated improved abductor strength at 16 weeks
      postsurgery. At 6 weeks, the patients with an anterior approach had improved late
      stance peak abductor moment postsurgery and reached the level of controls, but
      those with an anterolateral approach did not. Although the anterior approach was
      associated with improved gait velocity and peak flexor moments at 6 weeks
      compared to before surgery, we observed no differences between the two approaches
      for most of the isometric strength and dynamic gait measures at 6 or 16 weeks.
      Neither approach provided faster recovery.

PMID- 19763726
TI  - High union rates and function scores at midterm followup with ankle arthrodesis
      using a four screw technique.
AB  - When evaluating the role of ankle arthrodesis in the treatment of severe ankle
      arthritis, postoperative infection, nonunion, and the development of arthritis at
      the adjacent joints are major issues when considering treatment alternatives. We
      evaluated the rate of complications, the functional outcome, and compensatory
      range of motion at the midtarsal joint at medium-term followup after ankle
      arthrodesis with four cancellous screws. We performed 94 ankle fusions in 92
      patients; 12 patients were lost to followup and eight declined to participate,
      leaving 72 patients (76%) for evaluation. The minimum followup was 4.8 years
      (mean, 5.9; range, 4.8-7.8 years). No patient developed a deep infection; three
      patients developed postoperative hematoma which we operatively drained. Union
      occurred in 93 of the 94 patients (99%). The sagittal motion at the midtarsal
      joint averaged 24 degrees . Secondary arthritis of the subtalar and talonavicular
      joints developed during the followup period in 17% and 11%, respectively.
      Progression of preexisting arthritis occurred in 13 of 43 patients (30%) at the
      subtalar joint and five of 26 patients (19%) at the talonavicular joint. None of
      these patients had fusion of an adjacent joint. The average American Orthopaedic
      Foot and Ankle Society score increased from 36 preoperatively to 85 at followup.
      Ankle arthrodesis with screws provides high rates of union, reliable pain relief,
      and favorable functional medium-term results. LEVEL OF EVIDENCE: Level IV,
      therapeutic study. See Guidelines for Authors for a complete description of
      levels of evidence.

PMID- 19763727
TI  - Prognosis and coronary computed tomographic angiography: current and emerging
      concepts.

PMID- 19763728
TI  - The value of multi-slice-computed tomography  coronary angiography for risk
      stratification.
AB  - Multi-slice-computed tomography coronary angiography (CTA) provides direct non
      invasive anatomic assessment of the coronary arteries allowing for early
      identification of coronary artery disease (CAD). This information is useful for
      diagnosis of CAD, particularly the rule out of CAD. In addition, early
      identification of CAD with CTA may also be useful for risk stratification. The
      purpose of this review is to provide an overview of the current literature on the
      prognostic value of CTA and to discuss how the prognostic information obtained
      with CTA can be used to further integrate the technique into clinical practice.
      Non-invasive anatomic assessment of plaque burden, location, composition, and
      remodeling using CTA may provide prognostically relevant information. This
      information has been shown to be incremental to the Framingham risk score,
      coronary artery calcium scoring, and myocardial perfusion imaging.
      Characterization of atherosclerosis non-invasively has the potential to provide
      important prognostic information enabling a more patient-tailored approach to
      disease management.Future studies assessing outcome after CTA-based risk
      adjustments are needed to further understand the value of detailed non-invasive
      anatomic imaging.

PMID- 19763729
TI  - Abnormal myocardial perfusion in the absence of anatomically significant coronary
      artery disease: implications and clinical significance.

PMID- 19763731
TI  - Airway topicalization during tracheal intubation using the Airtraq laryngoscope
      in anesthetized patients.

PMID- 19763732
TI  - Evaluating outcomes in ultrasound-guided regional anesthesia.

PMID- 19763733
TI  - Branched-chain amino acids induce neurotoxicity in rat cortical cultures.
AB  - The higher risk for amyotrophic lateral sclerosis (ALS) among professional soccer
      players, recently reported in Italy, has stimulated investigations in the search
      for environmental factors that may be at the origin of the increased
      susceptibility to the disease. Here we studied if high concentrations of branched
      chain amino acids (BCAAs), widely used among athletes as dietary integrators to
      improve physical performance, may be related to an excitotoxic neuronal cell
      damage. Our results show that (i) high concentrations of BCAAs are neurotoxic and
      increase excitotoxicity in cortical neurons; (ii) neurotoxicity is brain area
      specific, being detected in cortical, but not in hippocampal neurons; (iii) it is
      related to NMDA receptor overstimulation, since it is abolished in the presence
      of MK-801, a specific NMDA channel blocker; (iv) it depends on the presence of
      astrocytes. We describe here a possible biological link between an environmental
      factor (high dietary intake of BCAAs) and the increased risk of ALS among soccer
      players.

PMID- 19763734
TI  - Glutamate carboxypeptidase inhibition reduces the severity of chemotherapy
      induced peripheral neurotoxicity in rat.
AB  - Chemotherapy is the most common method to treat cancer. The use of certain
      antineoplastic drugs, however, is associated with the development of peripheral
      neuropathy that can be dose-limiting. Excitotoxic glutamate release, leading to
      excessive glutamatergic neurotransmission and activation of N-methyl-D-aspartate
      (NMDA) receptors, is associated with neuronal damage and death in several nervous
      system disorders. N-Acetyl-aspartyl-glutamate (NAAG) is an abundant neuropeptide
      widely distributed in the central and peripheral nervous system which is
      physiologically hydrolyzed by the enzyme glutamate carboxypeptidase into N-Acetyl
      aspartyl (NAA) and glutamate. Pharmacological inhibition of glutamate
      carboxypeptidase results in decreased glutamate and increased endogenous NAAG and
      has been shown to provide neuroprotection in several preclinical models. Here, we
      report the neuroprotective effect of an orally available glutamate
      carboxypeptidase inhibitor on three well-established animal models of
      chemotherapy (cisplatin, paclitaxel, bortezomib)-induced peripheral neuropathy.
      In all cases, glutamate carboxypeptidase inhibition significantly improved the
      chemotherapy-induced nerve conduction velocity deficits. In addition,
      morphological and morphometrical alterations induced by cisplatin and bortezomib
      in dorsal root ganglia (DRG) were improved by glutamate carboxypeptidase
      inhibition. Our data support a novel approach for the treatment of chemotherapy
      induced peripheral neuropathy.

PMID- 19763735
TI  - Lipoteichoic acid induces matrix metalloproteinase-9 expression via
      transactivation of PDGF receptors and NF-kappaB activation in rat brain
      astrocytes.
AB  - Bacterial infections have been shown to be involved in several inflammatory
      diseases such as brain inflammation. A major factor for these findings is due to
      the secretion of pro-inflammatory mediators by host cells triggered by the
      components released from the bacteria. Among these components, lipoteichoic acid
      (LTA), a component of Gram-positive bacterial cell wall, has been found to be
      elevated in cerebrospinal fluid of patients suffering from meningitis. Moreover,
      increased plasma levels of matrix metalloproteinases (MMPs), in particular MMP-9,
      have been observed in patients with brain inflammatory diseases and may
      contribute to disease pathology. However, the molecular mechanisms underlying LTA
      induced MMP-9 expression in rat brain astrocytes (RBA-1 cells) remain poorly
      defined. Here, the data with zymographic, Western blotting, RT-PCR, and
      immunofluorescent staining analyses showed that LTA induced MMP-9 expression and
      activation via a TLR2-activated c-Src-dependent transactivation of PDGFR pathway.
      Transactivation of PDGFR led to activation of PI3K/Akt and p42/p44 MAPK and then
      activated the IKK/NF-kappaB cascade. The activated-NF-kappaB translocated into
      nucleus which bound to kappaB-binding site of MMP-9 promoter, and thereby turned
      on transcription of MMP-9. Eventually, upregulation of MMP-9 by LTA enhanced cell
      migration of astrocytes. Taken together, these results suggested that in RBA-1
      cells, activation of NF-kappaB by a c-Src-dependent PI3K/Akt-p42/p44 MAPK
      activation mediated through transactivation of PDGFR is essential for MMP-9 gene
      upregulation induced by LTA. Understanding the regulation of MMP-9 expression and
      functional changes by LTA/TLR system on astrocytes may provide potential
      therapeutic targets of Gram-positive bacterial infection in brain disorders.

PMID- 19763736
TI  - Endoplasmic reticulum stress plays critical role in brain damage after cerebral
      ischemia/reperfusion in rats.
AB  - The endoplasmic reticulum(ER) stress plays a vital role in mediating ischemic
      neuronal cell death. However, very little is known about the role of ER stress in
      mediating pathophysiological reactions to acute brain injuries. An attempt was
      therefore made to assess the role of cerebral ischemia/reperfusion (I/R) induced
      ER stress and its modulation on outcome of ischemic insult. Focal cerebral
      ischemia was induced in rats by middle cerebral artery occlusion (MCAO) for 2 h
      followed by varying time points of reperfusion. The brain loci specific and time
      dependent alterations were seen in the expression pattern of molecular markers,
      i.e., heat-shock protein 70 (HSP70) for cytoplasmic dysfunction, glucose
      regulated protein 78 (GRP78), Caspase-12, C/EBP homologous protein/growth arrest
      and DNA damage-inducible gene 153 (CHOP/GADD153), activating transcription factor
      4 (ATF-4), and Processed X-box protein 1 (xbp1) mRNA for ER dysfunction. Further,
      histological examinations indicated pronounced brain damage, massive neuronal
      loss, and DNA fragmentation predominantly in the striatum and cortex. The
      enhanced expression of GRP78, Caspase-12, CHOP/GADD153, ATF4 and processing of
      xbp1 mRNA in the affected brain regions clearly indicate the critical involvement
      of ER-mediated cell death/survival mechanisms and also collectively demonstrated
      the activation of unfolded protein response (UPR). Moreover, Salubrinal, a
      selective inhibitor of eIF2alpha dephosphorylation was used to counteract ER
      stress, which significantly increased the phosphorylation of eukaryotic
      translation initiation factor 2 subunit alpha (eIF2alpha), leading to reduced
      brain damage after I/R injury. Therefore, inhibition of ER stress following I/R
      injury may be used as key therapeutic target for neuroprotection.

PMID- 19763737
TI  - Mitochondrial uncoupling protein-2 (UCP2) mediates leptin protection against MPP+
      toxicity in neuronal cells.
AB  - Mitochondrial dysfunction is involved in the pathogenesis of neurodegenerative
      diseases, including Parkinson's disease (PD). Uncoupling proteins (UCPs) delink
      ATP production from biofuel oxidation in mitochondria to reduce oxidative stress.
      UCP2 is expressed in brain, and has neuroprotective effects under various toxic
      insults. We observed induction of UCP2 expression by leptin in neuronal cultures,
      and hypothesize that leptin may preserve neuronal survival via UCP2. We showed
      that leptin preserved cell survival in neuronal SH-SY5Y cells against MPP+
      toxicity (widely used in experimental Parkinsonian models) by maintaining ATP
      levels and mitochondrial membrane potential (MMP); these effects were accompanied
      by increased UCP2 expression. Leptin had no effect in modulating reactive oxygen
      species levels. Stable knockdown of UCP2 expression reduced ATP levels, and
      abolished leptin protection against MPP+-induced mitochondrial depolarization,
      ATP deficiency, and cell death, indicating that UCP2 is critical in mediating
      these neuroprotective effects of leptin against MPP+ toxicity. Interestingly,
      UCP2 knockdown increased UCP4 expression, but not of UCP5. Our findings show that
      leptin preserves cell survival by maintaining MMP and ATP levels mediated through
      UCP2 in MPP+-induced toxicity.

PMID- 19763738
TI  - Mechanisms involved in the modulation of astroglial resistance to oxidative
      stress induced by activated microglia: antioxidative systems, peroxide
      elimination, radical generation, lipid peroxidation.
AB  - Microglia and astrocytes are the cellular key players in many neurological
      disorders associated with oxidative stress and neuroinflammation. Previously, we
      have shown that microglia activated by lipopolysaccharides (LPS) induce the
      expression of antioxidative enzymes in astrocytes and render them more resistant
      to hydrogen peroxide (H2O2). In this study, we examined the mechanisms involved
      with respect to the cellular action of different peroxides, the ability to
      detoxify peroxides, and the status of further antioxidative systems. Astrocytes
      were treated for 3 days with medium conditioned by purified quiescent (microglia
      conditioned medium, MCM[-]) or LPS-activated (MCM[+]) microglia. MCM[+] reduced
      the cytotoxicity of the organic cumene hydroperoxide in addition to that of H2O2.
      Increased peroxide resistance was not accompanied by an improved ability of
      astrocytes to remove H2O2 or an increased expression/activity of peroxide
      eliminating antioxidative enzymes. Neither peroxide-induced radical generation
      nor lipid peroxidation were selectively affected in MCM[+] treated astrocytes.
      The glutathione content of peroxide resistant astrocytes, however, was increased
      and superoxide dismutase and heme oxygenase were found to be upregulated. These
      changes are likely to contribute to the higher peroxide resistance of MCM[+]
      treated astrocytes by improving their ability to detoxify reactive oxygen
      radicals and oxidation products. For C6 astroglioma cells a protective effect of
      microglia-derived factors could not be observed, underlining the difference of
      primary cells and cell lines concerning their mechanisms of oxidative stress
      resistance. Our results indicate the importance of microglial-astroglial cell
      interactions during neuroinflammatory processes.

PMID- 19763739
TI  - Sensory imbalance as mechanism of orientation disruption in the leafminer
      Phyllocnistis citrella: elucidation by multivariate geometric designs and
      response surface models.
AB  - Experimental designs developed to address mixtures are suited ideally to many
      areas of experimental biology, including pheromone blend studies, because such
      designs address the confounding of proportionality and concentration intrinsic to
      factorial and one-factor-at-a-time designs. Geometric multivariate designs
      coupled with response surface modeling allowed us to identify optimal blends of a
      two-component pheromone for attraction and trap disruption of the leafminer moth,
      Phyllocnistis citrella, a major pest in citrus growing areas around the world.
      Field trials confirmed that the natural 3:1 blend of (Z,Z,E)-7,11,13
      hexadecatrienal:(Z,Z)-7,11-hexadecadienal was most effective as an attractant for
      male moths. However, the response surface generated in mating orientation trials
      revealed that the triene component alone was more effective than the natural
      blend in disrupting trap catch. Each individual component was effective at
      disrupting orientation in field trials, but (Z,Z,E)-7,11,13-hexadecatrienal was
      approximately 13 times more effective, at the same concentration, compared with
      (Z,Z)-7,11-hexadecadienal alone. In addition, the application of geometric design
      and response surface modeling to field studies provided insight into a possible
      mechanism of mating disruption and supported sensory imbalance as the operating
      mechanism for this species.

PMID- 19763740
TI  - Congenital bilateral Morgagni's hernia secondary to twin accessory hepatic lobes
      in an infant.
AB  - Bilateral Morgagni's hernia is rare in infants. We report a rare case of
      bilateral anterio-medial defect in the diaphragm in a 5-month-old infant
      presenting with recurrent respiratory tract infection. He had two adjacent
      accessory hepatic lobes which, presumably, had embryologically caused the defect.
      He also had secondary herniation of the transverse colon without any symptoms
      attributable to it. We describe the management of this condition and the
      concerned literature is reviewed.

PMID- 19763741
TI  - Dimensions of the myopectineal orifice: a human cadaver study.
AB  - BACKGROUND: In mesh implantations, there needs to be a balance between mass and
      the size of the meshes. However, the mesh size should allow for adequate
      prevention of hernia recurrence by sufficient coverage of the entire myopectineal
      orifice (MPO). AIM AND OBJECTIVE: The aim was to determine the MPO dimensions and
      several pelvic parameters. METHODS: Thirty-two inguinal regions were assessed in
      16 embalmed cadavers. RESULTS: The MPO averaged 7.8 cm (+/-3.0) in width and 6.5
      cm (+/-1.9) in height. The weak inguinal area cranially to the inguinal ligament
      was 4.5 cm (+/-1.7) high. We found significant gender differences: MPOs in males
      showed the same width and height (7.6 x 7.6 cm), whereas in females, the MPO
      width was greater than its height (8.1 x 5.3 cm). Noticeable correlations of the
      MPO parameters to constitutional parameters were found for body size versus the
      height of the MPO (r = 0.5005) and interspinous distance versus the height of the
      MPO (r = 0.7653). CONCLUSIONS: A mesh measuring 10 x 8 cm is suitable for both
      genders: in females, it will cover the whole MPO, including the infraligamental
      part, whereas in males, the weak inguinal area is preferentially covered.

PMID- 19763742
TI  - A molecular and physiological survey of a diverse collection of hydrothermal vent
      Thermococcus and Pyrococcus isolates.
AB  - Strains of hyperthermophilic anaerobic hydrothermal vent archaea maintained in
      the culture collection assembled by Holger Jannasch at the Woods Hole
      Oceanographic Institution between 1984 and 1998 were identified and partially
      characterized by Denaturing Gradient Gel Electrophoresis, 16S rRNA gene
      sequencing, and by growth tests at different temperatures and on different
      organic carbon and nitrogen sources. All strains were members of the genera
      Thermococcus and Pyrococcus. The greatest phylogenetic diversity was found in
      strains from a single Guaymas Basin core isolated by serial dilution from four
      different depth horizons of heated sediment incubated at the corresponding in
      situ temperatures. In contrast, geographically distinct vent locations and sample
      materials yielded a lower diversity of isolates when enriched under uniform
      temperature regimes and without prior dilution of the source material.

PMID- 19763743
TI  - Maintaining high hemoglobin levels improved the left ventricular mass index and
      quality of life scores in pre-dialysis Japanese chronic kidney disease patients.
AB  - BACKGROUND: Anemia is common among patients with chronic kidney disease (CKD).
      The introduction of erythropoietin treatment has changed anemia management, but
      the therapeutic hemoglobin (Hb) target is still under debate, and clinical
      evidence for its effect on cardiac functions and QOL is sparse. METHODS: A 16
      week dose-response study and a 32-week follow-Up study were combined. After
      correcting anemia of less than 10 g/dl in pre-dialysis Japanese CKD patients, a
      higher Hb target (12-13 g/dl) by darbepoetin alfa (DPO) was compared with the
      conventional Hb target by epoetin alfa (EPO). Outcomes were anemia correction,
      management of the left ventricular mass index (LVMI) and QOL scores. RESULTS: No
      significant difference was seen in Hb at baseline and week 16, but a significant
      difference was recorded at week 34 (12.34 +/- 0.93 g/dl for DPO and 10.43 +/-
      0.90 g/dl for EPO). In both groups, LVMI decreased similarly until week 16, but
      the decrease of EPO was retarded, and a significant difference between LVMI was
      seen only in DPO at week 34 (100.7 +/- 16.6 g/m(2) for DPO and 110.9 +/- 25.2
      g/m(2) for EPO). Relationships between Hb and LVMI change at week 34 were
      examined by stratifying Hb into four groups (Hb <10 g/dl, 10 g/dl < or = Hb <11
      g/dl, 11 g/dl < or = Hb <12 g/dl and 12 g/dl < or = Hb), and a decrease of LVMI
      was prominent in the 12 g/dl < or = Hb group. Correction of anemia to 11 g/dl or
      more led to improved QOL scores. No safety difference was observed among the
      treatments. CONCLUSIONS: Targeting a higher Hb around 12 g/dl was more beneficial
      than targeting conventional Hb in terms of reduction of LVMI and QOL. Further
      studies to determine the appropriate Hb target are necessary.

PMID- 19763744
TI  - Productivity and quality of volatile oil extracted from Mentha spicata and M.
      arvensis var. piperascens grown by a hydroponic system using the deep flow
      technique.
AB  - The purpose of this study was to determine the differences between spearmint
      (Mentha spicata L.) and Japanese mint (M. arvensis L. var. piperascens Malinv.)
      cultivated in either soil or nutrient solution using the deep flow technique
      (DFT). The differences were measured in terms of harvest period (full bloom
      period) and quantity and chemical components of volatile oils. The spearmint and
      Japanese mint were cultivated in four different nutrient formulas: plant standard
      nutrient, plant standard nutrient with an amino acid mixture, plant standard
      nutrient with a sulphur compound, and a combination of plant standard nutrient
      with an amino acid mixture and a sulphur compound. We observed that cultivation
      of spearmint and Japanese mint in nutrient solution using DFT is an effective
      method to provide high production of volatile oil, since it results in an earlier
      harvest period and higher quantity of volatile oil. We determined that for
      spearmint an amino acid mixture is an appropriate nutrient supplement to enhance
      production of volatile oil with optimum carvone content. Finally, we observed
      high menthol content in Japanese mint grown in all four nutrient formulas;
      however, supplementation with a combination of sulphur fertilisation and amino
      acid mixture yields the highest quantity of volatile oil.

PMID- 19763745
TI  - Sequential adenovirus infection of type 14 hemorrhagic cystitis and type 35
      generalized infection after cord blood transplantation.
AB  - We report a case of a 29-year-old male patient with a generalized adenovirus
      (AdV) infection after cord blood transplantation (CBT) for acute myelocytic
      leukemia with maturation at 2nd complete remission. Before engraftment,
      hemorrhagic cystitis was caused by AdV, which resulted in hydronephrosis, renal
      failure, and adenoviremia on day 34. Forced diuresis, hemodialysis, withdrawal of
      cyclosporin A, and administration of gamma-globulin or vidarabine were not
      effective and the patient died of pulmonary alveolar hemorrhage on day 67. At
      autopsy, old inflammatory change only was observed in the bladder section. In the
      lungs and kidneys, granular deposits in the nucleus and a high copy number of AdV
      DNA were observed. Molecular diagnosis using PCR-restriction fragment length
      polymorphism analysis demonstrated that AdV with the serotype 14 caused the
      cystitis. However, retrospective genome typing using PCR sequencing revealed the
      infection of AdV serotype 35 in the kidneys, lungs, and serum. The present case
      suggested that Adv infection could not be always caused by a single AdV serotype,
      and suggested that multiple serotype infection was very difficult to treat. It is
      desired that a consensus regarding the treatment of AdV infections is
      established.

PMID- 19763747
TI  - Origins of retinal intrinsic signals: a series of experiments on retinas of
      macaque monkeys.
AB  - Diffuse flash stimuli applied to the ocular fundus evoke light reflectance
      decreases of the fundus illuminated with infrared observation light. This
      phenomenon, which is independent of the photopigment bleaching observed as an
      increase in the reflectance of visible light, is called intrinsic signals.
      Intrinsic signals, in general, are stimulus-evoked light reflectance changes of
      neural tissues due to metabolic changes, and they have been extensively
      investigated in the cerebral cortex. This noninvasive objective technique of
      functional imaging has good potential as a tool for the early detection of
      retinal dysfunction. Once the signal properties were studied in detail, however,
      it became apparent that the intrinsic signals observed in the retina have
      uniquely interesting properties of their own due to the characteristic layered
      structure of the retina. Experiments on anesthetized macaque monkeys are
      reviewed, and the possible origins of the intrinsic signals of the retina are
      discussed.

PMID- 19763748
TI  - Techniques for extraction of depth-resolved in vivo human retinal intrinsic
      optical signals with optical coherence tomography.
AB  - PURPOSE: To demonstrate acquisition and analysis methods for depth-resolved
      observation of slow retinal physiology induced changes in infrared backscatter in
      vivo. METHODS: A dark-adapted human was briefly subjected to a localized
      photobleach. For 20 min before and 30 min after the stimulus, volumetric optical
      coherence tomograms were collected partially overlapping the bleached region.
      Tomograms were segmented into retinal layers by a newly described algorithm
      exploiting information in adjacent B-scans. En face fundus images extracted from
      major intraretinal layers were laterally registered manually. Time series
      summarizing the observed backscatter in selected layers for the bleached and
      unbleached areas are shown with a variety of corrections and normalizations
      applied: tomograms were corrected for inherent sensitivity roll-off, and the
      ratio between other layers and an assumed unchanging layer (retinal pigment
      epithelium), as well as the ratio of the stimulated area to the unstimulated
      area, were calculated. RESULTS: Adjacent B-scan information allows a simpler
      segmentation algorithm to be used. Sensitivity roll-off correction reduces signal
      variability due to eye motion. After normalizations, the signal correlated with
      the stimulus appears strongest at the photoreceptor inner-outer segment junction.
      CONCLUSIONS: Demonstrated methods manage data complexity and reduce uncorrelated
      signal variability. This single trial warrants further investigation of intrinsic
      optical signals to observe slow physiologic responses.

PMID- 19763749
TI  - Intrinsic optical signal imaging of retinal activation.
AB  - Fast intrinsic optical signals (IOSs) correlated with stimulus-activated retinal
      responses are reviewed. Fast IOSs have a time course comparable to the stimulus
      evoked electrophysiological kinetics of the retina, and thus promise a new
      methodology for high-resolution evaluation of the physiological health of the
      retina. However, practical application of fast IOSs for retinal study and
      diagnosis is challenging because of their low sensitivity and limited
      specificity. Using isolated amphibian retinas, a series of experiments to
      optimize and characterize fast IOSs has been conducted. Fast, high-resolution
      nearinfrared light imaging disclosed both positive (increasing) and negative
      (decreasing) optical responses in adjacent retinal areas, which satisfied spatial
      resolution essential to the differentiation of IOSs from opposite polarities. At
      the subcellular (approximately microm) level, fast IOSs often exceeded 5%
      DeltaI/I, where I is the dynamic optical change, and I is the background light
      intensity. Experiments with isolated frog retinas suggest that negative IOSs stem
      primarily from the photoreceptor layer, while positive IOSs come from inner
      retinal layers.

PMID- 19763750
TI  - Noninvasive functional imaging of the retina reveals outer retinal and
      hemodynamic intrinsic optical signal origins.
AB  - We have adapted intrinsic signal optical imaging of neural activity to the
      noninvasive functional imaging of the retina. Results to date demonstrate the
      feasibility and potential of this new method of functional assessment of the
      retina. In response to visual stimuli, we have imaged reflectance changes in the
      retina that are robust and spatially colocalized to the sites of stimulation.
      However, the technique is in its infancy and many questions as to the underlying
      mechanisms remain. In particular, the source and nature of the activity-dependent
      intrinsic optical signals in the retina need to be characterized and their
      anatomic origins determined. The studies described here begin to address these
      issues. The evidence indicates that the imaged signals are driven by the outer
      retinal layers and have a dominant hemodynamic component.

PMID- 19763751
TI  - Functional imaging using the retinal function imager: direct imaging of blood
      velocity, achieving fluorescein angiography-like images without any contrast
      agent, qualitative oximetry, and functional metabolic signals.
AB  - The Retinal Function Imager (RFI; Optical Imaging, Rehovot, Israel) is a unique,
      noninvasive multiparameter functional imaging instrument that directly measures
      hemodynamic parameters such as retinal blood-flow velocity, oximetric state, and
      metabolic responses to photic activation. In addition, it allows capillary
      perfusion mapping without any contrast agent. These parameters of retinal
      function are degraded by retinal abnormalities. This review delineates the
      development of these parameters and demonstrates their clinical applicability for
      noninvasive detection of retinal function in several modalities. The results
      suggest multiple clinical applications for early diagnosis of retinal diseases
      and possible critical guidance of their treatment.

PMID- 19763752
TI  - Magnetic resonance imaging of the retina.
AB  - This paper reviews recent developments in high-resolution magnetic resonance
      imaging (MRI) and its application to image anatomy, physiology, and function in
      the retina of animals. It describes technical issues and solutions in performing
      retinal MRI, anatomical MRI, blood oxygenation level-dependent functional MRI
      (fMRI), and blood-flow MRI both of normal retinas and of retinal degeneration.
      MRI offers unique advantages over existing retinal imaging techniques, including
      the ability to image multiple layers without depth limitation and to provide
      multiple clinically relevant data in a single setting. Retinal MRI has the
      potential to complement existing retinal imaging techniques.

PMID- 19763753
TI  - Base curves of therapeutic lenses and their effects on post Epi-LASIK vision and
      pain: a prospective randomized clinical trial.
AB  - PURPOSE: To compare the efficacy of bandage contact lenses with two different
      base curves in promoting epithelial healing after epithelial laser in situ
      keratomileusis (epi-LASIK). METHODS: A prospective, observer-masked study was
      conducted in 27 patients. Each patient randomly received one bandage contact lens
      with an 8.4-mm base curve in one eye and one with an 8.8-mm base curve in the
      fellow eye. Corneal epithelial status, pain score, spherical equivalent, and
      uncorrected visual acuity (UCVA) were examined during the first postoperative
      month. RESULTS: Corneal epithelial status, postoperative pain, and spherical
      equivalent were similar for both lenses during the first postoperative month. The
      eyes with lenses with an 8.8-mm base curve had better UCVA on postoperative day
      (POD) 4, but there was no significant difference in UCVA after POD 7. In the
      patients with preoperative low to moderate myopia and low keratometric values
      (<43.0 D), there was no significant difference in the postoperative UCVA between
      the lenses. On the other hand, in patients with preoperative high myopia and high
      keratometric values (> or =43.0 D), UCVA was better in eyes with lenses with an
      8.8-mm base curve on POD 4. CONCLUSIONS: These findings suggest that the base
      curves of bandage contact lenses affect visual rehabilitation after epi-LASIK,
      particularly in patients with a steep cornea and high myopia.

PMID- 19763754
TI  - Conjunctival vasculature patterns influencing the filtering bleb shape following
      trabeculectomy with limbal-based conjunctival flaps.
AB  - PURPOSE: To investigate the correlation between conjunctival vasculature factors
      and two types of functional bleb shape, cystic and diffuse, formed after
      trabeculectomy with limbal-based conjunctival flaps. METHODS: Eighty-five eyes of
      glaucoma patients were consecutively enrolled. After 6 months, functioning blebs
      were classified as either cystic or diffuse. For each bleb type, the presence of
      neovascularized vessels in the dissected area (NVc) or the nondissected area
      (NVi), an avascular area (AVA), or a posterior tarsal artery (PTA) feeding the
      conjunctiva was analyzed. RESULTS: In 62 eyes with functioning blebs, there were
      54 cystic and eight diffuse blebs. AVA was present in 96.3% of the cystic and
      25.0% of the diffuse blebs. NVc was present in 100% of the cystic and 62.5% of
      the diffuse blebs, and NVi in 96.3% of the cystic and 12.5% of the diffuse blebs.
      A PTA was present in 87.5% of the diffuse blebs, but in only 3.7% of the cystic
      blebs. AVA, NVi, and NVc were significantly more frequent in cystic blebs,
      whereas a PTA was more frequent in diffuse blebs. The presence of a PTA in the
      blebs was negatively related to the presence of AVA, NVc, or NVi. CONCLUSIONS:
      Avoidance of damage to the PTA during conjunctival dissection might facilitate
      the formation of a diffuse filtration bleb. The conjunctival vasculature should
      be considered to avoid cystic avascular bleb formation in trabeculectomy with
      limbal-based flaps.

PMID- 19763755
TI  - Progression of optic neuropathy after disc hemorrhage in primary angle-closure
      glaucoma.
AB  - BACKGROUND: We describe progressive optic neuropathy after recurrent disc
      hemorrhages in patients with primary angle-closure glaucoma. CASES: Three
      Taiwanese Chinese patients with primary angle-closure glaucoma and recurrent disc
      hemorrhages were followed for 10 years. OBSERVATIONS: Despite good control of
      intraocular pressure, progressive enlargement of optic disc cupping and visual
      field defects corresponding to the location of disc hemorrhages were noted after
      recurrent hemorrhages. CONCLUSIONS: Disc hemorrhages are not particularly rare in
      primary angle-closure glaucoma and may be a sign of a poor prognosis.

PMID- 19763756
TI  - Ocular manifestations and prognosis of shaken baby syndrome in two Japanese
      children's hospitals.
AB  - PURPOSE: To distinguish the profiles of patients and ophthalmologic features and
      to describe the prognosis of shaken baby syndrome (SBS) in Japan. METHODS: Charts
      of child abuse cases involving retinal hemorrhage at Kanagawa Children's Medical
      Center and the National Center for Child Health and Development between January
      1997 and December 2007 were retrospectively reviewed. The mean follow-up period
      was 22.2 months (range, 0-115 months). RESULTS: Twenty-one boys and 11 girls were
      identified. The mean age at the initial visit was 7.0 months (range, 4 days to 17
      months). Four boys died during hospitalization. Seventeen eyes of ten patients
      (31%) had vitreous hemorrhage; 16 eyes of eight patients (25%) had a more
      favorable ocular prognosis with no apparent complications. Eight infants (25%)
      had been born prematurely. The mean maternal age was 29.9 years, and mothers were
      the primary perpetrator in 19 cases (59%). CONCLUSIONS: The clinical features of
      SBS in Japan are comparable to those in the Western literature. However, we have
      also found some idiosyncratic features in Japanese SBS cases; the mother is more
      frequently the perpetrator and abusive parents are older than in the United
      States, possibly reflecting current trends in Japan toward later marriage.

PMID- 19763757
TI  - One-year results of intravitreal ranibizumab for neovascular age-related macular
      degeneration and clinical responses of various subgroups.
AB  - PURPOSE: To report 1-year clinical outcomes of intravitreal ranibizumab treatment
      for choroidal neovascularization (CNV) due to age-related macular degeneration
      (AMD) and to identify predictive factors that may influence visual acuity (VA)
      outcomes in Korean patients. METHODS: Sixty patients (64 eyes) with subfoveal CNV
      were followed up over 12 months after intravitreal injection (0.5 mg) of
      ranibizumab at baseline and subsequent injections on an as-needed basis. The VA
      outcomes over 12 months were compared with baseline VA and evaluated across
      subgroups based on sex, age, baseline VA, CNV size, CNV type, and presence or
      absence of systemic disease and prior photodynamic therapy. RESULTS: VA improved
      or remained stable in 46 of 64 eyes (71.9%) at 12 months. Subgroup analysis
      showed that both baseline VA and CNV size influenced VA outcomes after
      ranibizumab treatment (P = 0.039, P = 0.042, respectively). However, the
      patients' sex (P = 0.643), baseline age (P = 0.361), CNV type (P = 0.940), and
      the presence or absence of systemic disease (P = 0.775) and prior photodynamic
      therapy (P = 0.890) did not affect VA outcomes. CONCLUSIONS: Intravitreal
      injections of ranibizumab improve mean VA in patients with subfoveal CNV
      secondary to AMD, and baseline VA and CNV lesion size were predictive factors of
      VA outcomes after ranibizumab treatment in Korean patients.

PMID- 19763758
TI  - Association of clinical characteristics with disease subtypes, initial visual
      acuity, and visual prognosis in neovascular age-related macular degeneration.
AB  - PURPOSE: To comprehend the clinical characteristics and factors related to visual
      prognosis in two major subtypes of neovascular age-related macular degeneration
      (AMD)-traditional, typical AMD and polypoidal choroidal vasculopathy (PCV).
      METHODS: Medical records of 272 eyes of 216 patients diagnosed with neovascular
      AMD at Kyoto University Hospital between January 2000 and March 2003 were
      retrospectively reviewed for up to 3 years. Ophthalmoscopic, angiographic, and
      optical coherence tomography (OCT) findings were collected, and univariate and
      multivariate analyses were performed to determine the characteristic factors, the
      factors associated with initial visual acuity (VA), and visual prognosis in
      typical AMD and PCV. RESULTS: We studied 154 eyes with typical AMD and 117 eyes
      with PCV. The presence of classic choroidal neovascularization (CNV) and
      posterior confluent drusen were characteristic of typical AMD, whereas PCV was
      characterized by a larger number of retinal pigment epithelial detachments and a
      small number of drusen. Poor initial VA (<0.1) was significantly associated with
      subfoveal classic CNV, hard exudates, late fibrosis staining of >or =1 disc area
      in AMD, and with blood and cystoid macular edema in PCV. Maintenance of good VA
      was associated with better initial VA in typical AMD and with smaller lesions in
      PCV. CONCLUSION: Typical AMD and PCV revealed statistical differences both in
      their clinical characteristics and in the factors associated with visual
      prognosis.

PMID- 19763759
TI  - Orbital venous anomaly presenting with orbital hemorrhage.
AB  - PURPOSE: To report on the characteristics of patients with orbital venous anomaly
      presenting with acute orbital hemorrhage. METHODS: We retrospectively reviewed
      the clinical and radiologic findings of a case series of eight orbital venous
      anomaly patients who presented with orbital hemorrhage. Charts of patients
      diagnosed as having orbital venous anomaly who initially presented with orbital
      hemorrhage were selected. RESULTS: The eight patients with orbital venous anomaly
      (one man and seven women) ranged in age from 7 to 66 years (median, 22 years).
      The average duration of symptoms was 7 days (range, 1-30 days). All eight
      patients were totally asymptomatic prior to their acute presentations. Orbital
      computed tomography (CT) scans showed a well-demarcated ovoid mass in all eight
      patients. Five patients were referred with a suspicion of orbital tumor, and one
      underwent a lateral orbitotomy for a biopsy. In six patients, the presence of an
      orbital hemorrhage was identified by typical findings on orbital magnetic
      resonance imaging (MRI). After resolution of the hemorrhage, all patients
      evidenced a distensible orbital venous anomaly in an imaging study. CONCLUSION:
      An orbital venous anomaly presenting with sudden orbital hemorrhage can be
      mistaken for other orbital tumors. In patients with acute orbital process,
      orbital MRI for detecting hemorrhage and a follow-up CT scan after resolution of
      the hemorrhage are needed to prevent unnecessary surgical intervention.

PMID- 19763760
TI  - Effect of higher order aberrations on contrast sensitivity function in myopic
      eyes.
AB  - PURPOSE: To evaluate the relation between higher order aberrations (HOAs) and
      contrast sensitivity function (CSF) in a population with myopia. METHODS: In this
      case series, HOAs were measured in 70 myopic eyes over a 6-mm pupil. Contrast
      sensitivity was also measured. From the contrast sensitivity data, the area under
      the log contrast sensitivity function (AULCSF) was calculated. Pupil diameter was
      measured under photopic conditions. RESULTS: Seventy right eyes of 70 myopic
      subjects with a mean age of 26.6 +/- 5.7 years were studied. The mean spherical
      equivalent and refractive astigmatism were -4.97 +/- 1.6 D and 0.93 +/- 0.5 D,
      respectively. AULCSF was significantly but negatively correlated with the
      cycloplegic spherical equivalent (r (2) = 0.57, P = 0.02), the root mean square
      (RMS) of total HOAs (r (2) = 0.065, P = 0.03), the RMS of fourth-order
      aberrations (r (2) = 0.089, P = 0.015), and the RMS of the spherical aberration
      (r (2) = 0.037, P = 0.004). AULCSF did not have any significant association with
      age, photopic pupil diameter, refractive astigmatism, or the RMS of the coma
      aberration. CONCLUSION: Spherical and fourth-order aberrations significantly
      affect CSF in myopic eyes. However, the effect of myopia on CSF cannot be
      attributed only to HOAs. Other factors such as neural elements in the visual
      pathway should be taken into account.

PMID- 19763761
TI  - Linezolid-associated optic neuropathy in a patient with ocular sarcoidosis.
AB  - BACKGROUND: We describe a case of bilateral linezolid-associated optic neuropathy
      in a patient with ocular sarcoidosis. CASE: A 70-year-old woman with sarcoidosis
      noted foggy vision in both eyes. Best-corrected visual acuity was 0.5 in the
      right eye and 0.9 in the left. No abnormality other than slight optic disc
      hyperemia was visible in either eye. A central scotoma in both eyes and
      enlargement of the blind spot in the right eye were detected by Goldmann
      perimetry examination, and magnetic resonance imaging demonstrated an edematous
      optic nerve in the right eye. Therefore, retrobulbar optic neuritis resulting
      from sarcoidosis was initially suspected. Sub-Tenon's capsule injection of
      triamcinolone acetonide along with steroid pulse therapy was given; however, best
      corrected visual acuity worsened to 0.06 in the right eye and 0.08 in the left.
      Pulse therapy was discontinued on day 1, and the possibility of linezolid
      associated optic neuropathy was speculated because linezolid had been given for
      methicillin-resistant Staphylococcus aureus osteomyelitis 2 years before by an
      orthopedist. After discontinuation of linezolid, best-corrected visual acuity
      improved to 0.8 in the right eye and 0.9 in the left, and the optic disc
      hyperemia in both eyes disappeared. CONCLUSION: Our findings demonstrate that it
      is important for ophthalmologists as well as physicians and orthopedists to
      consider the possibility of optic neuropathy caused by long-term use of
      linezolid.

PMID- 19763762
TI  - Minimum endotoxin concentration causing inflammation in the anterior segment of
      rabbit eyes.
AB  - PURPOSE: This was a quantitative study to investigate the minimum endotoxin
      concentration causing inflammation in the anterior segment of the eye. METHODS:
      Endotoxin was injected intracamerally in pigmented rabbits. A quantitative
      determination of flare and cells in the aqueous was performed using a laser flare
      cell photometer, before and until 72 h after the treatment. An area under the
      curve (AUC) analysis was employed to evaluate the whole inflammatory reaction
      regarding flare values. RESULTS: The time course of flare values in each
      endotoxin group showed a similar pattern with a peak value at 3 h. An AUC
      corresponding to values for "average +2sigma", 19301.8 in control eyes, was
      considered the cutoff value. Using this cutoff value and the regression curve in
      endotoxin-treated groups, the minimum endotoxin concentration causing
      inflammation regarding flare values was determined to be 0.60 endotoxin units
      (EU). Cell counts (cells/0.5 mm(3).0.5 s) corresponding to the value "average
      +2sigma", 6.07 at 24 h, in control eyes was considered to be the cutoff value.
      The minimum endotoxin concentration regarding cell counts was determined to be
      0.23 EU. CONCLUSION: There was a dissociation in response between flare and cells
      in the aqueous to intracameral endotoxin. The minimum endotoxin concentration
      causing inflammation ranged between 0.23 and 0.60 EU.

PMID- 19763763
TI  - Sub-Tenon's injection of triamcinolone for optic disc neovascularization in a
      patient with retinitis pigmentosa.

PMID- 19763764
TI  - Unilateral hemi-central retinal vein obstruction associated with retinal racemose
      angioma.

PMID- 19763765
TI  - Diagnostic Western blot for lens-specific proteins in aqueous fluid after
      traumatic lens-induced uveitis.

PMID- 19763766
TI  - Uveitis associated with sarcoidosis exacerbated by etanercept therapy.

PMID- 19763767
TI  - A case of compressive optic neuropathy caused by sphenoid sinus cholesterol
      granuloma.

PMID- 19763768
TI  - A case of orbital lipoma with exophthalmos and visual disturbance.

PMID- 19763769
TI  - Headache induced by isolated sphenoid fungal sinusitis: sinus headache?
AB  - In this article, we report a case of isolated sphenoid fungal sinusitis which
      only presented as headache. We review the literature of this rare but interesting
      lesion according to the revised 2004 IHS diagnostic criteria for "Headache
      attributed to Rhinosinusitis".

PMID- 19763770
TI  - Pain perception and laser evoked potentials during menstrual cycle in migraine.
AB  - The association between estrogens "withdrawal" and attacks of migraine without
      aura is well-known. The aim of the study was to examine the features of laser
      evoked potentials (LEPs), including habituation, in women suffering from migraine
      without aura versus healthy controls, during the pre-menstrual and late luteal
      phases. Nine migraine without aura and 10 non-migraine healthy women, were
      evaluated during the pre-menstrual phase and late luteal phase. The LEPs were
      recorded during the inter-critical phase. The right supraorbital zone and the
      dorsum of the right hand were stimulated. Three consecutive series of 20 laser
      stimuli were obtained for each stimulation site. Laser pain perception was rated
      by a 0-100 VAS after each stimulation series. Migraine patients exhibited
      increased LEPs amplitude and reduced habituation compared to normal subjects.
      Laser-pain perception was increased during the pre-menstrual phase in both
      patients and controls. Migraine patients and controls showed increased P2 and N2
      P2 amplitude in the pre-menstrual phase, on both stimulation sites. During the
      pre-menstrual phase the N2-P2 habituation appeared to be reduced in both migraine
      and healthy women. The estrogen withdrawal occurring during the menstrual cycle
      may favor reduced habituation of nociceptive cortex, which may facilitate pain
      symptoms and migraine in predisposed women.

PMID- 19763771
TI  - Bilateral SUNCT-like headache in a patient with prolactinoma responsive to
      lamotrigine.
AB  - Short-lasting unilateral neuralgiform headache with conjunctival injection and
      tearing (SUNCT) syndrome is a rare trigeminal autonomic cephalalgia. The cases of
      SUNCT with attacks that affected both sides simultaneously have only rarely been
      reported and some of them had underlying pathology. We have reported a case of
      bilateral SUNCT-like headache secondary to a prolactinoma and responsive to
      lamotrigine treatment.

PMID- 19763772
TI  - Comprehensive autonomic assessment does not differentiate between Parkinson's
      disease, multiple system atrophy and progressive supranuclear palsy.
AB  - Differential diagnosis of parkinsonian syndromes is a major challenge in movement
      disorders. Dysautonomia is a common feature but may vary in clinical severity and
      onset. The study attempted to find a pattern of autonomic abnormalities
      discriminative for patients with different parkinsonian syndromes. The cross
      sectional study included 38 patients with multiple system atrophy (MSA), 32
      patients with progressive supranuclear palsy (PSP), 26 patients with idiopathic
      Parkinson's disease (IPD) and 27 age-matched healthy controls. Autonomic symptoms
      were evaluated by a standardized questionnaire. The performance of patients and
      controls was compared on five autonomic function tests: deep breathing, Valsalva
      manoeuvre, tilt-table testing, sympathetic skin response, pupillography, and 24-h
      ambulatory blood pressure monitoring (ABPM). Disease severity was significantly
      lower in IPD than PSP and MSA. Except for pupillography, none of the laboratory
      autonomic tests distinguished one patient group from the other alone or in
      combination. The same was observed on the questionnaire. Receiver operating
      characteristic curve revealed discriminating performance of pupil diameter in
      darkness and nocturnal blood pressure change. The composite score of urogenital
      and vasomotor domains significantly distinguished MSA from IPD patients but not
      from PSP. Our study supports the observation that even mild IPD is frequently
      indistinguishable from more severe MSA and PSP. Thus, clinical combination of
      motor and non-motor symptoms does not exclusively point at MSA. Pupillography,
      ABPM and the questionnaire may assist in delineating the three syndromes when
      applied in combination.

PMID- 19763773
TI  - Mitochondria in neurodegenerative disorders: regulation  of the redox state and
      death signaling leading  to neuronal death and survival.
AB  - In Parkinson's disease, impaired function of mitochondrial complex I is involved
      in selective degeneration of dopamine neurons in the substantia nigra.
      Mitochondria are now considered to play an active role in neuronal death process
      through activating "intrinsic" apoptotic signaling, in addition to production of
      reactive oxygen species. This paper presents our recent findings on new functions
      of mitochondria in regulation of their redox state and function through
      reversible "S-glutathionylation", a mixed disulfide binding between sulfhydryl
      groups of GSH and protein cysteine in complex I subunits. Type A monoamine
      oxidase (MAO-A) localized at the mitochondrial outer membrane is a binding site
      of neurotoxins leading to apoptosis. Rasagiline and (-)deprenyl, type B MAO
      inhibitors of propagylamine-derivatives, bind to MAO-A to protect neuronal cells
      against apoptosis through induction of pro-survival Bcl-2 and neurotrophic
      factors. This review discusses the new role of mitochondria in regulation of
      neuronal cell death of neurodegenerative disorders.

PMID- 19763774
TI  - Admission of Parkinsonian patients to a neurological  ward in a community
      hospital.
AB  - Hospitalization is a significant factor contributing to health care costs related
      to management of Parkinson's disease (PD) patients. We reviewed reasons for
      admission of PD patients to our Neurological Department over a 6-year period.
      Thereafter, we applied an "open door" policy to try to diminish the number of
      hospitalizations. Case records including patient data, disease duration, staging,
      reasons for admission, and motor, mental and general medical status of PD
      patients admitted to the Neurology Department over a 6-year period were reviewed.
      Out of 1,920 admissions, 143 were PD patients. All PD admissions were through the
      emergency department (non-elective). Motor complications were the reason for
      admission in 37%, psychosis in 24%, general medical problems in 14%, and a
      combination of motor and psychiatric in 25%. Drug-induced psychosis was the most
      significant cause of repeated and prolonged admissions (29% of patients). As
      motor and psychiatric complications are the commonest causes for admission,
      improved community-based care to "fine tune" medication appeared to be a
      priority. After analyzing our results, we instituted an "open door" policy, where
      patients are free to come to the Parkinson's clinic without appointment. This
      policy should improve control of PD symptoms and diminish hospitalizations.

PMID- 19763775
TI  - Characterization of NS3 protease from an Egyptian HCV genotype 4a isolate.
AB  - The role of the NS3 protease in HCV replication was demonstrated by the ability
      of a protease inhibitor cocktail (10 microg/ml) to abolish the induced cytopathic
      effect in RAW macrophages upon infection with Egyptian sera. The HCV protease
      gene was amplified from Egyptian sera by nested PCR and cloned downstream of the
      CMV promotor in a mammalian expression plasmid, which was then used to transform
      bacteria. Colonies carrying the gene in the correct orientation were subjected to
      large-scale plasmid purification followed by sequencing. Phylogenetic comparison
      of the sequence obtained with published sequences from different genotypes
      confirmed that our sequence belongs to genotype 4a. Of the other genotypes, the
      most closely related ones were from genotype 1. Multiple alignments of protease
      peptides showed that the catalytic triads and binding residues for substrate,
      Zn2+ and the NS4 cofactor are conserved among different isolates, including ours,
      and confirmed the closer homology between NS3 of genotypes 4 and 1. The HCV
      protease-encoding construct was successfully transcribed in both mammalian cells
      and mice. Mouse antibodies produced against the protease-encoding-construct
      detected the 18-kDa enzyme in lysates of cells transfected with the construct by
      Western blotting, and in the media of infected cells by ELISA.

PMID- 19763776
TI  - Molecular characterization of a rare, human-porcine reassortant rotavirus strain,
      G11P[6], from Ecuador.
AB  - The Pan-American Health Organization established a rotavirus pre-vaccination
      disease burden and strain surveillance network in Latin America and the Caribbean
      in 2004. During strain surveillance in Ecuador in 2005-2006, a rare rotavirus
      genotype, G11P[6], was detected among common strains. Sequencing and phylogenetic
      analysis of this strain identified a novel lineage of the G11 VP7 gene, most
      closely related to A253 (91.8% nt identity), a porcine rotavirus strain
      identified in Venezuela. Most genes of this strain clustered with porcine, human
      porcine or bovine-porcine reassortant strains; only VP6 and perhaps NSP2 genes
      were more closely related to cognate genes of human rotaviruses. Thus, this
      strain was likely generated by gene reassortment between porcine and human
      parental strains. Our study provides further evidence that animal rotaviruses
      play an important role in genetic and antigenic diversity of rotaviruses
      pathogenic for humans.

PMID- 19763777
TI  - Immunogenicity and efficacy of a bacterially expressed HEV ORF3 peptide, assessed
      by experimental infection of primates.
AB  - A 12.4-kDa peptide, corresponding to the entire ORF3 protein of hepatitis E virus
      (HEV), derived from human HEV genotype 4 and expressed in Escherichia coli as a
      fusion protein with a 17.5-kDa fragment of interleukin (IL)-1beta at the N
      terminus, was recognized by HEV-reactive sera. Eight monkeys were immunized with
      the purified peptide, and seven were used as non-immunized controls. All 15
      monkeys were challenged with HEV genotype 1 or 4. All control animals developed
      infection and hepatitis, and all but one vaccinated monkey became infected.
      Nevertheless, the vaccine was effective in reducing the virus titer and
      shortening the duration of viremia and fecal shedding. Furthermore, the vaccine
      provided some protection against hepatitis (1 of 2 monkeys in the two-dose
      regimen and 4 of 6 in the three-dose regimen did not develop severe hepatitis)
      compared to the controls. These results suggest that immunization with the
      bacterially expressed peptide may partially prevent experimental hepatitis, and
      even infection, in primates, following intravenous challenge with high doses of
      two HEV genotypes.

PMID- 19763778
TI  - Effects of hepatitis C virus envelope glycoprotein unfolded protein response
      activation on translation and transcription.
AB  - The hepatitis C virus (HCV) envelope glycoproteins have been shown to cause ER
      stress and induce the unfolded protein response (UPR). Using a bicistronic
      reporter, we show that the envelope glycoproteins repressed both cap-dependent
      and HCV IRES-mediated translation in HeLa cells but displayed a differential
      repression of cap-dependent translation in Huh-7 cells. In contrast, the envelope
      glycoproteins repressed E2F transcriptional activity in both HeLa and Huh-7 cells
      and caused increased accumulation of the underphosphorylated retinoblastoma
      protein. Expression of the envelope glycoproteins induced eIF2alpha
      phosphorylation, suggesting a role of the UPR in regulating translation and E2F
      transcriptional activity. The envelope glycoproteins also enhanced
      transcriptional activity from the COX-2 promoter and endogenous COX-2 expression
      in HeLa cells, but not in Huh-7 cells. Together, these results suggest that the
      envelope glycoproteins may assume more functional roles in viral replication and
      host cell interactions.

PMID- 19763779
TI  - Molecular detection and prevalence of porcine caliciviruses in eastern China from
      2008 to 2009.
AB  - Caliciviruses causing diarrhea have been reported in both industrial and
      developing countries, including China, in recent years. Porcine caliciviruses
      that are closely related to human sapoviruses (SaVs) and noroviruses (NoVs) have
      also been detected in swine, which has raised discussion about the animal
      reservoir and the potential risk for zoonotic transmission to humans. The
      objective of this work was to determine the frequency and age distribution of
      SaVs and NoVs in pigs and to characterize the strains prevalent in eastern China.
      A total of 904 stool samples from pigs of different ages were collected from
      eastern China from April 2008 to March 2009 and tested for both SaVs and NoVs
      using reverse transcription-polymerase chain reaction (RT-PCR). Our results
      indicate that 8 (0.9%) stool samples were positive for SaVs and 2 (0.2%) for
      NoVs. Phylogenetic analysis of partial sequences of the RNA-dependent RNA
      polymerase (RdRp) gene indicated that all of the SaV strains belonged to the GIII
      SaVs, while the two NoV strains belonged to the GII NoV genogroup. The 8 SaV
      strains were further divided into two clusters, which clustered closely with the
      Netherlands isolate (AY615804) and the Chinese strain (EU599212), respectively.
      The two NoV strains shared about 67.3-67.6% nucleotide homology with a human
      norovirus strain (DQ369797), the only NoV strain from mainland China available in
      GenBank. Moreover, our results suggest that SaV infections are more frequent in 0
      1 month-old pigs than in older ones. In conclusion, the present study provides
      evidence that PoSaVs and PoNoVs exist in swine in eastern China.

PMID- 19763780
TI  - Identification of a new pathotype of Bean yellow mosaic virus (BYMV) infecting
      blue passion flower and some evolutionary characteristics of BYMV.
AB  - The modes of molecular evolution of the coat protein (CP) and 3' non-coding
      region (NCR) were investigated in Bean yellow mosaic virus (BYMV) isolates,
      including a new pathotype from blue passion fruit. In phylogenetic analysis, the
      new pathotype did not cluster with pathotypes or host groups described
      previously. Intraspecific recombinations involving the entire 3'-NCR and a
      variable portion of the 3'-terminal region of the CP gene were detected between a
      broad bean isolate and several isolates from monocots. Since the predicted
      secondary structure of the 3'-NCR correlated mostly with the botanical origin of
      isolates, a possible role of the 3'-NCR in BYMV host adaptation is proposed and
      discussed.

PMID- 19763781
TI  - Comparison of the activities of BM2 protein and its H19 and W23 mutants of
      influenza B virus with activities of M2 protein and its H37 and W41 mutants of
      influenza A virus.
AB  - Co-expression of the BM2 protein with pH-sensitive HA reduces the conversion of
      HA to its low-pH conformation during transport to the cell surface in the same
      way as human M2 proteins. BM2 protein is capable of increasing vesicular pH by as
      much as 0.4 pH units. Mutation analysis showed that replacement of H19 in BM2
      protein by A and L resulted in loss of activity, while M2, with the mutation
      H37A, remained active, but its severe toxicity was intolerable for cells. Whereas
      substitution of L or A for W23 abolished detectable activity of the BM2 channel,
      substitution of L for W41 in the M2 protein resulted in a functional ion channel
      but with reduced activity. W41 was not essential for functional activity of the
      M2 protein. Our results show some differences in the nature of the interaction of
      the histidine and tryptophan in the transmembrane domains of BM2 and M2 ion
      channels.

PMID- 19763782
TI  - Interaction of lipid bodies with other cell organelles in the maturing pollen of
      Magnolia x soulangeana (Magnoliaceae).
AB  - The pollen grain maturation in Magnolia x soulangeana was studied
      ultrastructurally and cytochemically using both the light and transmission
      electron microscope. Emphasis was given on the storage lipid bodies of the
      vegetative cell (VC) and their interaction with other cell organelles.
      Stereological analysis of electron micrographs was performed to evaluate the
      variation in volume density (V(V)), surface density, and surface-to-volume ratio
      (S/V) of various cell organelles during pollen maturation. The size and numerical
      density of the lipid bodies, and their frequency of association with other cell
      organelles, were also determined. It was noted that during pollen ontogeny and
      maturation, the lipid bodies changed their pattern of distribution in the VC
      cytoplasm, which may be a good marker for the succeeding stages of pollen
      development. Also, the size, osmiophily, and V(V) of the lipid bodies were
      progressively reduced during pollen maturation whereas the S/V was significantly
      increased. This seems to indicate that the lipid bodies are mobilized in part
      during this period of pollen maturation. In particular, the intermediate and
      mature pollen showed a high percentage of lipid bodies establishing a physical
      contact with either glyoxysomes, either protein storage vacuoles, or small
      vesicles presumably originated from dictyosomes. This physical contact was found
      in both the chemically fixed and rapid freeze-fixed pollen indicating that it is
      neither artifactual nor casual. On the basis of this intimate association with
      other cell organelles and the morphometric analysis performed, we suggest that
      the mobilization of lipid bodies is likely mediated not only by glyoxysomes but
      also by other catabolic pathways involving the interaction of lipid bodies with
      either protein storage vacuoles or small Golgi vesicles.

PMID- 19763783
TI  - Oxidative defence reactions in sunflower roots induced by methyl-jasmonate and
      methyl-salicylate and their relation with calcium signalling.
AB  - Ca(2+) plays a critical role as second messenger in the signal-response coupling
      of plant defence responses, and methyl-jasmonate and methyl-salicylate are
      important components of signal transduction cascades activating plant defences.
      When intact axenic non-induced seedling roots of sunflower were treated with
      different Ca(2+) concentrations up to 1 mM, there was no significant increase in
      O(2)(*-) generation or DMAB-MBTH peroxidase (extracellular, ECPOX) activities in
      the apoplast, probably because these roots had enough Ca(2+) in their exo- and
      endocellular reservoirs. Both activities were strongly inhibited by the RBOH
      NADPH oxidase inhibitor DPI and by the Ca(2+) surrogate antagonist La(3+), but
      the voltage-dependent Ca(2+) channel blocker verapamil was only inhibitory at
      concentrations higher than those active on animal L-type Ca(2+) channels.
      Concentrations >5 mM EGTA (chelating Ca(2+) in the apoplast) and Li(+)
      (inhibiting PI cycle dependent endogenous Ca(2+) fluxes) also inhibited both
      activities. W7, inhibitor of binding of Ca-CaM to its target protein, enhanced
      both activities, but the inactive analogue W5 showed a similar effect. Our data
      suggest that Ca(2+) from exocellular and, to a lesser extent, from endocellular
      stores is involved in oxidative activities, and that RBOH-NADPH oxidase is the
      main system supporting them. Ca(2+) activation of the PM cytosolic side of RBOH
      NADPH oxidase is probably the key to Ca(2+) involvement in these processes. Roots
      induced by MeJA or MeSA showed significant enhancement of both oxidative
      activities, as corresponding to the oxidative burst evoked by the two
      phytohormones in the root apoplast. But while ECPOX activity showed a response to
      the effectors similar to that described above for non-induced roots, O(2)(*-)
      generation activity in the apoplast of induced roots was insensitive to EGTA,
      verapamil and Li(+), the inhibitors of exogenous and endogenous Ca(2+) fluxes;
      only DPI and La(3+) were inhibitory. As exogenously added 0.1 mM Ca(2+) also
      increased O (2) (.-) generation, we propose that, in these roots, activation of
      RBOH-NADPH oxidase by Ca(2+) could be regulated by Ca(2+) sensors in the
      apoplast.

PMID- 19763784
TI  - Chemiluminescence from thermal oxidation of amino acids and proteins.
AB  - Chemiluminescence (CL) with maximum emission in the range 550-650 nm is observed
      when proteins and certain amino acids are heated in air, and CL intensity is
      significantly reduced in nitrogen. Of the 20 common amino acids, lysine (Lys) has
      the highest thermal CL intensity by a factor of approximately 30 over arginine,
      threonine and asparagine. This finding differs from previous studies on amino
      acids and proteins oxidised using free radical initiators or singlet oxygen,
      where tryptophan was the dominant factor for CL emission. CL from heating solid
      Lys in air is accompanied by browning and the generation of fluorescent products
      which are characteristic of advanced glycosylation end products (AGEs) in
      thermally treated milk proteins. During thermal oxidation, Lys may react with its
      own carbonyl oxidation products to form fluorescent compounds similar to AGEs via
      the formation of Schiff bases. The mechanism of thermal oxidation of proteins may
      be similar to polyamide polymers, where reaction of free primary amino groups
      with carbonyls to form Schiff bases plays a key role.

PMID- 19763785
TI  - Aqueous-phase quantitative NMR determination of amino acid enantiomer ratio by
      13C-NMR using chiral neodymium shift reagent.
AB  - A neodymium-(S)-PDTA (PDTA = N,N,N',N'-tetrakis[(hydroxycarbonyl)methyl]-1,2
      diaminopropane) complex was found exceptionally useful in the quantitative
      determination of enantiomer ratios of water-soluble natural amino acids by (13)C
      NMR. The method is demonstrated on mixtures of L- and D-enantiomers of various
      amino acids. The interactions of the chiral shift reagent with the amino acid
      molecules were rationalized by molecular orbital calculations.

PMID- 19763787
TI  - Immunosuppressive effects of mesenchymal stem cells in collagen-induced mouse
      arthritis.
AB  - OBJECTIVE: The objective of this study was to investigate the efficacy of
      mesenchymal stem cell (MSC) in the treatment of arthritis. METHODS: Mesenchymal
      stem cells were injected intravenously into mice with collagen-induced arthritis
      (CIA). Arthritic indexes were evaluated, and the levels of the pro- and anti
      inflammatory cytokines interleukin-10 (IL-10), gamma interferon (IFN-gamma)
      inducible protein 10 (IP-10), chemokine (C-X-C motif) receptor 3 (CXCR3),
      interleukin-17A (IL-17A), and tumor necrosis factor alpha (TNF-alpha) in serum or
      splenic cells were determined using real-time RT-PCR, Western blotting, and
      enzyme-linked immunosorbent assay (ELISA). The proliferation of dendritic cell
      line D2SC cells was determined using (3)H-TdR incorporation assay. RESULTS: Upon
      injection of MSCs, overall arthritis symptoms were significantly improved in the
      CIA mouse models as indicated by the paw edema. Consistent with this observation,
      serum levels of pro-inflammatory cytokine TNF-alpha and inflammatory cell
      infiltration decreased significantly 12 days after MSC injection, while the
      expression of anti-inflammatory cytokines IL-10, IP-10, and CXCR3 was increased
      in splenocytes. In addition, we provided evidence that MSCs may directly promote
      the proliferation of D2SC cells and the expression of IP-10 in D2SC cells in
      vitro. CONCLUSION: Mesenchymal stem cells significantly enhance the efficacy of
      collagen-induced arthritis treatment, likely through the modulation of the
      expression of various cytokines.

PMID- 19763788
TI  - IL-33 synergizes with IgE-dependent and IgE-independent agents to promote mast
      cell and basophil activation.
AB  - OBJECTIVE: Mast cell and basophil activation contributes to inflammation,
      bronchoconstriction, and airway hyperresponsiveness in asthma. Because IL-33
      expression is inflammation inducible, we investigated IL-33-mediated effects in
      concert with both IgE-mediated and IgE-independent stimulation. METHODS: Because
      the HMC-1 mast cell line can be activated by GPCR and RTK signaling, we studied
      the effects of IL-33 on these pathways. The IL-33- and SCF-stimulated HMC-1 cells
      were co-cultured with human lung fibroblasts and airway smooth muscle cells in a
      collagen gel contraction assay. IL-33 effects on IgE-mediated activation were
      studied in primary mast cells and basophils. RESULT: IL-33 synergized with
      adenosine, C5a, SCF, and NGF receptor activation. IL-33-stimulated and SCF
      stimulated HMC-1 cells demonstrated enhanced collagen gel contraction when
      cultured with fibroblasts or smooth muscle cells. IL-33 also synergized with IgE
      receptor activation of primary human mast cells and basophils. CONCLUSION: IL-33
      amplifies inflammation in both IgE-independent and IgE-dependent responses.

PMID- 19763789
TI  - Antioxidant, anti-inflammatory and analgesic potential of the Citrus decumana L.
      peel extract.
AB  - The present study was designed to investigate the antioxidant, anti-inflammatory
      and analgesic potential of Citrus decumana peel extract. Antioxidant activity of
      Citrus decumana peel extract in four solvent systems was evaluated by 1,1
      diphenyl-2-picrylhydrazyl (DPPH(.)) and hydrogen peroxide (H(2)O(2)) radical
      scavenging methods. Ethyl acetate peel extract of Citrus decumana (EtCD) was
      studied for its anti-inflammatory and analgesic activities at a dose level of
      100, 200 and 300 mg/kg. Anti-inflammatory activity was performed using
      carrageenan-induced paw edema in rats. Analgesic activity was evaluated for its
      central and peripheral pharmacological actions in mice. EtCD showed significant
      antioxidant activity in a dose-dependent manner when compared with ascorbic acid.
      EtCD at the dose of 300 mg/kg produced significant decrease in paw volume and
      pain when compared with reference drug diclofenac and morphine, respectively. The
      Citrus decumana peel extract may be useful as a natural antioxidant in the
      treatment of inflammation and pain.

PMID- 19763790
TI  - Neurocognitive training in patients with high-grade glioma: a pilot study.
AB  - Although their neurocognitive performance is one of the major concerns of
      patients with high-grade gliomas (HGG) and although neurocognitive deficits have
      been described to be associated with negative outcome, neurocognitive
      rehabilitation is usually not integrated into the routine care of patients with
      malignant gliomas. In this pilot trial, a weekly group training session for
      attention, verbal, and memory skills was offered to patients with HGG with pre
      and post-training evaluation. Eleven patients, six with glioblastoma multiforme
      and five with WHO grade III gliomas, median age 50 years, with a Karnofsky
      performance score of 80-100 participated in ten group training sessions of 90
      min. For evaluation at baseline and after the training by a neuropsychologist not
      involved in care or training of the patients, Trail Making Tests A and B (TMTA
      and TMTB), Hopkins Verbal Learning Test (HVLT), and the Controlled Oral Word
      Association Test (COWA) were used. Comparison of mean group differences between
      baseline and at post-training evaluation after 12 weeks revealed improvement
      across all neurocognitive variables. The patients showed a great diversity in
      their performances, with worsening, improvement, and stabilization. However, a
      significant group difference was detected only for the HVLT (score 19.6 +/- 8.9
      at baseline, 23.6 +/- 8.8 after 12 weeks, P = 0.04). This pilot study shows that
      neurocognitive training in patients with HGG is feasible as group training with
      weekly sessions and might be able to induce improvements in attention and memory
      skills.

PMID- 19763791
TI  - CoA Synthase is phosphorylated on tyrosines in mammalian cells, interacts with
      and is dephosphorylated by Shp2PTP.
AB  - CoA Synthase (CoASy, 4'-phosphopantetheine adenylyltransferase/dephospho-CoA
      kinase) mediates two final stages of de novo coenzyme A (CoA) biosynthesis in
      higher eukaryotes. Unfortunately very little is known about regulation of this
      important metabolic pathway. In this study, we demonstrate that CoASy interacts
      in vitro with Src homology-2 (SH2) domains of a number of signaling proteins,
      including Src homology-2 domains containing protein tyrosine phosphatase
      (Shp2PTP). Complexes between CoASy and Shp2PTP exist in vivo in mammalian cells
      and this interaction is regulated in a growth-factor-dependent manner. We have
      also demonstrated that endogenous CoASy is phosphorylated on tyrosine residues in
      vivo, and that cytoplasmic protein tyrosine kinases can mediate this
      phosphorylation in vitro and in vivo. Importantly, Shp2PTP-mediated CoASy in
      vitro dephosphorylation leads to an increase in CoASy enzymatic
      phosphopantetheine adenylyltransferase (PPAT) activity. We therefore argue that
      CoASy is a novel potential substrate of Shp2PTP and phosphorylation of CoASy at
      tyrosine residue(s) could represent unrecognized before mechanism of modulation
      intracellular CoA level in response to hormonal and (or) other extracellular
      stimuli.

PMID- 19763792
TI  - ERK activation and cell growth require CaM kinases in MCF-7 breast cancer cells.
AB  - Previous studies on MCF-7 breast cancer cells have shown that the G-protein
      coupled receptor (GPCR) agonist carbachol increases intracellular calcium levels
      and the activation of extracellular signal-regulated kinase (ERK). Calcium and
      calmodulin regulate the calcium/calmodulin-dependent kinase (CaM kinase) family
      of proteins that have been proposed to regulate ERK and gene transcription. Our
      results suggest that both estrogen (E2) and carbachol treatment of MCF-7 breast
      cancer cells trigger phosphorylation of ERK1/2 and the transcription factor Elk
      1. Carbachol and estrogen triggered nearly a four- to sixfold increase in MCF-7
      cell proliferation by 96 h, respectively. Carbachol-stimulated ERK activation and
      cell growth was completely blocked by the Muscarinic M(3)-subtype GPCR inhibitor,
      4-DAMP, and siRNA against the M(3)-subtype GPCR. Interestingly, blockade of CaM
      KK with the selective inhibitor STO-609 prevented carbachol activation CaM KI,
      ERK, Elk-1, and cell growth. Consistent with these observations, knockdown of CaM
      KKalpha and CaM KIgamma with shRNA-containing plasmids blocked ERK activation by
      carbachol. In addition, Elk-1 phosphorylation and luciferase activity in response
      to carbachol treatment was also dependent upon CaM kinases and was inhibited by
      U0126, STO-609, and siRNA knockdown of CaM kinases and ERK2. Finally, blockade of
      either CaM KK (with STO-609) or ERK (with U0126) activities resulted in the
      inhibition of carbachol- and estrogen-mediated cyclin D1 expression and MCF-7
      cell growth. Taken together, our results suggest that carbachol treatment of MCF
      7 cells activates CaM KI, ERK, the transcription factor Elk-1, cyclin D1, and
      cell growth through CaM KK.

PMID- 19763793
TI  - JNK1/2 siRNA inhibits transforming-growth factor-beta1-induced connective tissue
      growth factor expression and fibrotic function in THSFs.
AB  - Transforming-growth factor-beta1 (TGF-beta1) plays an important role in fibrosis
      by inducing connective tissue growth factor (CTGF) expression. In cornea,
      however, signaling pathway in the process is unclear. In this paper, real-time RT
      PCR and Western blot analysis were used to examine the expression and TGF-beta1
      induced upregulation of CTGF in telomerase-immortalized human cornea stroma
      fibroblast cells (THSFs). A detailed molecular mechanism for TGF-beta1-mediated
      cell proliferation and collagen I production was then investigated by detecting
      the activation of JNK pathway in TGF-beta1-stimulated THSFs and blocking the JNK
      pathway using JNK1/2 siRNA. Both TGF-beta1 and CTGF clearly induced cell
      proliferation in THSFs which was inhibited by functional blocking CTGF by anti
      CTGF antibody. Blocking JNK pathway by JNK1/2 siRNA significantly inhibited
      induction of CTGF by TGF-beta1. Taken together, the data indicate that CTGF is
      critical to the fibrosis process in wounded human cornea, acting via upregulation
      and activation of JNK signaling pathway.

PMID- 19763795
TI  - BCL2L12A localizes to the cell nucleus and induces growth inhibition through G2/M
      arrest in CHO cells.
AB  - BCL2L12, a newly identified member of Bcl-2 family, and its transcript variant
      BCL2L12A have been found to be associated with favorable prognosis in breast
      cancer patients while correlated with tumorigenesis of glioblastoma and colon
      cancer. However, the biological functions of BCL2L12 and especially those of
      BCL2L12A are largely unknown. Here, we report that, unlike other Bcl-2 family
      proteins, BCL2L12 and its transcript variant BCL2L12A are nuclear proteins.
      Interestingly, BCL2L12 forms speckle patterns in the nuclei and potently induces
      apoptosis in CHO cells. BCL2L12A had a diffuse distribution in the nuclei and
      inhibits cell growth by inducing cell cycle arrested at G2/M transition in CHO
      cells. More importantly, BCL2L12A-induced G2/M arrest was associated with a
      slight up-regulation of cyclin B1 and significant down-regulation of an active
      form of cyclin B1 phosphorylated at Ser147. Taken together, our study suggests
      that both BCL2L12 and BCL2L12A have negative effects on CHO cell growths, and
      that BCL2L12A is a potential cell cycle regulator that interferes with G2-M
      transition.

PMID- 19763796
TI  - Construction of collagen II/hyaluronate/chondroitin-6-sulfate tri-copolymer
      scaffold for nucleus pulposus tissue engineering and preliminary analysis of its
      physico-chemical properties and biocompatibility.
AB  - To construct a novel scaffold for nucleus pulposus (NP) tissue engineering, The
      porous type II collagen (CII)/hyaluronate (HyA)-chondroitin-6-sulfate (6-CS)
      scaffold was prepared using 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC)
      and N-hydroxysuccinimide (NHS) cross-linking system. The physico-chemical
      properties and biocompatibility of CII/HyA-CS scaffolds were evaluated. The
      results suggested CII/HyA-CS scaffolds have a highly porous structure (porosity:
      94.8 +/- 1.5%), high water-binding capacity (79.2 +/- 2.8%) and significantly
      improved mechanical stability by EDC/NHS crosslinking (denaturation temperature:
      74.6 +/- 1.8 and 58.1 +/- 2.6 degrees C, respectively, for the crosslinked
      scaffolds and the non-crosslinked; collagenase degradation rate: 39.5 +/- 3.4 and
      63.5 +/- 2.0%, respectively, for the crosslinked scaffolds and the non
      crosslinked). The CII/HyA-CS scaffolds also showed satisfactory cytocompatibility
      and histocompatibility as well as low immunogenicity. These results indicate
      CII/HyA-CS scaffolds may be an alternative material for NP tissue engineering due
      to the similarity of its composition and physico-chemical properties to those of
      the extracellular matrices (ECM) of native NP.

PMID- 19763797
TI  - The medical humanities: toward a renewed praxis.
AB  - In this essay, I explore medical humanities practice in the United States with
      descriptions offered by fifteen faculty members who participated in an electronic
      survey. The questions posed focused on the desirability of a core humanities
      curriculum in medical education; on the knowledge, skills, and values that are
      found in such a curriculum; and on who should teach medical humanities and make
      curriculum decisions regarding content and placement. I conclude with a call for
      a renewed interdisciplinarity in the medical humanities and a move away from the
      territorial aspects of disciplinary knowledge and methods sometimes found in
      medical humanities practice.

PMID- 19763798
TI  - B-cell reconstitution and BAFF after alemtuzumab (Campath-1H) treatment of
      multiple sclerosis.
AB  - INTRODUCTION: Treatment with alemtuzumab is highly effective in relapsing
      remitting multiple sclerosis; however, 30% of patients develop autoimmunity.
      Alemtuzumab (previously called Campath 1-H) induces a prolonged T-cell
      lymphopenia with memory cells dominating the reconstituting T-cell pool for at
      least 3 months. RESULTS: Here we show that B-cell recovery is rapid, returning to
      baseline by 3 months and rising to 165% of baseline by 12 months after treatment.
      Immature transitional 1 B cells are the predominant cell type 1 month after
      treatment. This coincides with a surge in serum B-cell activating factor (BAFF),
      which remains elevated by 33% for at least 12 months after alemtuzumab. BAFF is
      critical for transition to the mature naive B-cell phenotype, which dominates
      from 3 months after alemtuzumab. Differentiation to memory B cells is slow so
      there are radical and prolonged alterations to the B-cell pool after alemtuzumab.

PMID- 19763800
TI  - Belief and behavior aspects of the EAT-26: The case of schoolgirls in Belize.
AB  - This study investigates components of eating attitudes in a sample of Belizean
      schoolgirls and argues for separate analysis of eating beliefs and eating
      behaviors using the EAT-26 in populations undergoing rapid cultural change. The
      EAT-26 was utilized in a novel manner, preserving the ethnographic and empirical
      distinction between belief and behavior components of eating attitudes.
      Participants included a sample of secondary schoolgirls (n = 80) undergoing
      acculturative stress. Participants reported more disordered eating beliefs than
      behaviors. Respondents having higher belief scores than behavior scores were more
      likely to prefer thinner body build and to be concerned about boys' assessments
      of their bodies. Girls with higher behavior scores were less likely to report
      eating when hungry and stopping when full. In conclusion, discriminant validity
      was found between attitudinal and behavioral aspects of the EAT-26 as evidenced
      by face validity and patterns in predicting body image preference and desired
      weight change. Such a distinction has implications for assessing risk for
      disordered eating among populations undergoing acculturative stress. Among such
      populations, while behavioral symptoms might be absent or present in subclinical
      levels, disordered beliefs associated with psychological distress or potential
      precursors to eating-disordered behavior might be detected and should be
      investigated further.

PMID- 19763801
TI  - Revisiting parental monitoring: evidence that parental solicitation can be
      effective when needed most.
AB  - Studies using valid measures of monitoring activities have not found the
      anticipated main effects linking greater monitoring activity with fewer
      behavioral problems. This study focused on two contexts in which monitoring
      activities may be particularly influential. Early adolescents (n = 218, M age =
      11.5 years, 51% female, 49% European American, 47% African American) reported
      their unsupervised time, beliefs about the legitimacy of their parents'
      authority, and their own involvement in antisocial behavior. Mothers and
      adolescents reported their perceptions of adolescent disclosure and parental
      solicitation and control. Adolescents' perceptions of greater parental
      solicitation at age 11 were associated with less antisocial behavior at age 12
      (when controlling for age 11 antisocial behavior) among adolescents reporting
      large amounts of unsupervised time and weak legitimacy beliefs. Perceived
      parental solicitation may be an effective deterrent of antisocial behavior when
      adolescents spend a lot of time unsupervised and for adolescents who are likely
      to challenge the legitimacy of their parents' authority.

PMID- 19763802
TI  - Induction of NOS and nitrotyrosine expression in the rat striatum following
      experimental hepatic encephalopathy.
AB  - Hepatic encephalopathy (HE) is a neurologic disease associated with hepatic
      dysfunction. Astroglial and neuronal alterations have been described in the basal
      ganglia in HE. Our study was performed to determine whether such alterations are
      mediated by nitric oxide (NO), by using an experimental model of HE (portacaval
      anastomosis [PCA]). The expression of the NO synthases (nNOS and iNOS) and the
      production of nitrotyrosine (NT) were evaluated in the striatum of rats exposed
      to PCA for 1 and 6 months. The expression of nNOS in the striatal neurons of PCA
      rats was increased compared to controls. nNOS expression was also detectable in
      astrocytes after 6 months of exposure to PCA. Whereas astroglial cells in the
      normal striatum showed no iNOS expression, iNOS was expressed in the astrocytes
      of PCA brains, mainly in perivascular processes at 6 months PCA exposure
      (demonstrated by colocalization with GFAP). The increased expression of both the
      nNOS and iNOS isoforms in PCA rats might indicate a critical role for NO in the
      pathomechanism of HE. To study the potential cell damage caused by NO, the
      deposition of NT in PCA-rats was analysed. Nitrotyrosine was detected in neurons
      although it was mainly seen in the astrocytes of PCA brains, in which double
      immunolabelling showed NT to be colocalized with GFAP. Thus, the present study
      shows the induction of iNOS and NT in astrocytes, which increases with the
      duration of PCA exposure. This suggests that the induced astroglial production of
      NO during PCA might be one of the main factors contributing to HE.

PMID- 19763803
TI  - Azelnidipine and amlodipine anti-coronary atherosclerosis trial in hypertensive
      patients undergoing coronary intervention by serial volumetric intravascular
      ultrasound analysis in Juntendo university (ALPS-J).
AB  - PURPOSE: Many trials have shown that calcium channel blockers (CCBs) can reduce
      the cardiovascular (CV) events in patients with coronary artery disease (CAD).
      The mechanisms of this effect could be associated with plaque regression due to
      the anti-atherosclerotic properties of CCBs. The goal of this study is to
      determine the effects of CCB on volumetric quantitative changes of coronary
      plaques accessed by intravascular ultrasound (IVUS). To confirm this hypothesis,
      a multicenter randomized trial of CCBs treatment with azelnidipine or amlodipine
      will be conducted in hypertensive CAD patients undergoing elective percutaneous
      coronary intervention (PCI). METHODS AND RESULTS: Patients who have hypertension
      and are scheduled for PCI will be enrolled. Subjects will be randomized to
      azelnidipine or amlodipine and observed for 48 weeks. The primary endpoint will
      be the percent change of coronary plaque volume. The secondary endpoint will
      include inflammatory markers, antioxidant activity, and incidence of composite
      cardiovascular events. CONCLUSIONS: In this study, we will investigate the
      improvement of coronary plaque with IVUS by treatment with two dihydropyridine
      CCBs in hypertensive patients undergoing elective PCI. This result will lead to
      the discovery of more effective drug therapy for inhibition of coronary events.

PMID- 19763804
TI  - Endothelial cell seeding fails to prevent intimal hyperplasia following arterial
      injury in the rat carotid model.
AB  - PURPOSE: Aim of the study was to evaluate the therapeutic potential of
      endothelial cell seeding to inhibit the neointimal response after balloon injury
      of the rat carotid artery. METHODS AND RESULTS: Endothelial cells were isolated
      from peripheral blood after cytokine-stimulation (PB-EC), the bone marrow
      compartment (BM-EC), and the thoracic aorta (AO-EC) of male rats. The EC
      populations were characterized by microscopy, cytofluorometry, and PCR-analysis,
      and displayed distinct patterns of RNA-expression of the EC-markers VEGF-receptor
      1 and 2, and TIE2. 5 x 10(5) ECs were incubated in the freshly balloon-denuded
      arterial bed for 30 min achieving about 70% coverage with all 3 EC-populations.
      However, the neointimal response 2 weeks after the procedure was significantly
      aggravated in the EC-seeded carotids (I/M-ratio: non-seeded Control 1.00 +/-
      0.10, PB-EC 1.53 +/- 0.07, BM-EC 1.64 +/- 0.12, and AO-EC 1.55 +/- 0.14; P < 0.05
      vs. Control for all). We found evidence for an accelerated cell-turnover (TUNEL
      assay, total cell-density, infiltration with CD45(pos) haematopoietic cells)
      especially in the adventitia of the treated vessels. CONCLUSION: Endothelial cell
      seeding fails to prevent intimal hyperplasia following arterial injury in the rat
      carotid model.

PMID- 19763805
TI  - Brief report: Representational momentum for dynamic facial expressions in
      pervasive developmental disorder.
AB  - Individuals with pervasive developmental disorder (PDD) have difficulty with
      social communication via emotional facial expressions, but behavioral studies
      involving static images have reported inconsistent findings about emotion
      recognition. We investigated whether dynamic presentation of facial expression
      would enhance subjective perception of expressed emotion in 13 individuals with
      PDD and 13 typically developing controls. We presented dynamic and static
      emotional (fearful and happy) expressions. Participants were asked to match a
      changeable emotional face display with the last presented image. The results
      showed that both groups perceived the last image of dynamic facial expression to
      be more emotionally exaggerated than the static facial expression. This finding
      suggests that individuals with PDD have an intact perceptual mechanism for
      processing dynamic information in another individual's face.

PMID- 19763806
TI  - Investigation of mentalizing and visuospatial perspective taking for self and
      other in Asperger syndrome.
AB  - Mentalizing refers to making inferences about other people's mental states,
      whereas visuospatial perspective taking refers to inferring other people's
      viewpoints. Both abilities seem vital for social functioning; yet, their exact
      relationship is unclear. We directly compared mentalizing and visuospatial
      perspective taking in nineteen adults with Asperger syndrome (AS) and fifteen
      control participants with the same stimulus material. Stimuli depicted virtual
      characters surrounded by two different objects. Virtual characters expressed a
      preference for one of the objects indicated by facial expression, gestures or
      head/body orientation. Compared to controls, participants with AS showed
      significantly increased reaction times and decreased accuracy for mentalizing
      (i.e., when inferring the virtual character's preference from the character's
      nonverbal bodily cues). By contrast, there were no significant group differences
      in perspective taking (i.e., by mental own-body transformations). These findings
      demonstrate, first, specific deficits in AS when mental states have to be
      inferred from nonverbal social cues. Second, visuospatial perspective taking may
      not necessarily be related to social impairments occurring in autism spectrum
      disorders.

PMID- 19763807
TI  - Enhancing emotion recognition in children with autism spectrum conditions: an
      intervention using animated vehicles with real emotional faces.
AB  - This study evaluated The Transporters, an animated series designed to enhance
      emotion comprehension in children with autism spectrum conditions (ASC). n = 20
      children with ASC (aged 4-7) watched The Transporters everyday for 4 weeks.
      Participants were tested before and after intervention on emotional vocabulary
      and emotion recognition at three levels of generalization. Two matched control
      groups of children (ASC group, n = 18 and typically developing group, n = 18)
      were also assessed twice without any intervention. The intervention group
      improved significantly more than the clinical control group on all task levels,
      performing comparably to typical controls at Time 2. We conclude that using The
      Transporters significantly improves emotion recognition in children with ASC.
      Future research should evaluate the series' effectiveness with lower-functioning
      individuals.

PMID- 19763808
TI  - Theory of mind in adults with HFA and Asperger syndrome.
AB  - Theory of mind was assessed in 32 adults with HFA, 29 adults with Asperger
      syndrome and 32 neurotypical adults. The HFA and Asperger syndrome groups were
      impaired in performance of the Strange stories test and the Faux-pas test and
      reported more theory of mind problems than the neurotypical adults. The three
      groups did not differ in performance of the Eyes test. Furthermore, correlations
      between the Eyes test and the three other theory of mind tests were low or
      absent. Therefore one can question the ability of the Eyes test to measure theory
      of mind. Of all theory of mind tests used, the self-report questionnaire had the
      largest discriminating power in differentiating the two disorder groups from the
      neurotypical group.

PMID- 19763809
TI  - Introgression of Brown Norway chromosome 13 improves visual spatial memory in the
      Dahl S rat.
AB  - The present study was conducted in an effort to evaluate whether chromosomal
      substitution can repair impaired exploration learning and memory. It has
      previously been observed that Dahl salt-sensitive (SS) rodents exhibit impaired
      cognitive function along with abnormal physiological responses to muscle
      stimulation. Introgression of Brown Norway chromosome (13(BN)) has been found to
      restore normal physiological processes in SS animals. However, the effect of
      chromosomal substitution on cognitive performance has not been explored. It was
      hypothesized that 13(BN) also rescues cognitive impairments in these animals.
      Visual spatial learning and cognitive flexibility were evaluated using the Morris
      water maze (MWM) and the T-maze. This manipulation is effective in rescuing
      impaired task acquisition, but not perseveration observed in the SS animal. These
      animals may represent a natural animal model in which to isolate genetic
      information responsible for learning and memory function.

PMID- 19763810
TI  - Psychosocial characteristics and sexual behaviors of people in care for HIV
      infection: an examination of men who have sex with men, heterosexual men and
      women.
AB  - Few studies have examined the psychosocial factors associated with sexual
      transmission behaviors among HIV-positive men who have sex with men (MSM),
      heterosexual men (MSW) and women. We enrolled 1,050 sexually active HIV-positive
      patients at seven HIV clinics in six US cities as part of a clinic-based
      behavioral intervention. We describe the sexual transmission behaviors and
      examine demographic, clinical, psychosocial, and clinic prevention variables
      associated with unprotected anal or vaginal intercourse (UAVI). Twenty-three
      percent of MSM, 12.3% of MSW and 27.8% of women engaged in UAVI with partners
      perceived to be HIV-negative or of unknown serostatus. Among MSM and MSW, having
      multiple partners and lower self-efficacy were associated with increased odds of
      UAVI. Self-rating one's health status as excellent/very good was a risk factor
      for UAVI among MSM. Among women, binge drinking and stressful life events were
      associated with UAVI. These findings identify variables that warrant attention in
      targeted interventions.

PMID- 19763811
TI  - Factors associated with parent-child communication about HIV/AIDS in the United
      States and Kenya: a cross-cultural comparison.
AB  - This study explored parent-child communication about HIV/AIDS among two
      populations disproportionately affected by HIV. Similar computer-assisted surveys
      were completed by parents of pre-teens, including 1,115 African American parents
      of 9-12-year-old children in southeastern US and 403 parents of 10-12-year-old
      children in Nyanza Province, Kenya. Multivariate analyses identified factors
      associated with parental report of ever talking to their child about HIV/AIDS.
      Twenty-nine percent of US parents and 40% in Kenya had never talked to their pre
      teen about HIV/AIDS. In both countries, communication was more likely if parents
      perceived their child to be ready to learn about sex topics, had gotten
      information to educate their child about sex, and had greater sexual
      communication responsiveness (skill, comfort, and confidence communicating about
      sexuality). Programs are needed that help parents assess children's readiness to
      learn about sexual issues; access accurate information about adolescent sexual
      risks; and acquire the responsiveness needed to discuss sexual issues, including
      HIV/AIDS.

PMID- 19763812
TI  - Risk behaviors and psychosocial stressors in the new york city house ball
      community: a comparison of men and transgender women who have sex with men.
AB  - The New York City House Ball community consists of social networks of
      racial/ethnic minority gay, lesbian or bisexual men and women, and transgender
      persons. HIV seroprevalence and interview data were obtained from a sample of
      community members to identify statistical differences in HIV prevalence, risk
      behavior, and psychosocial stressors between men who have sex with men (MSM) and
      transgender women. Of 301 MSM and 60 transgender women, 20% were HIV-infected and
      73% were unaware of their infection, but rates did not differ by gender. Risk
      behavior and stressors were common in both groups, but transgender women were
      more likely to report exchange sex, stigmatization, and stressful life events.
      High rates of risk behavior and HIV in this special community warrant relevant
      HIV testing and prevention services. Transgender women in the community may be at
      even greater risk for HIV infection due to behaviors compounded by substantial
      psychosocial stressors.

PMID- 19763813
TI  - Comparing couples' and individual voluntary counseling and testing for HIV at
      antenatal clinics in Tanzania: a randomized trial.
AB  - Voluntary counseling and testing (VCT) for couples (CVCT) is an important HIV
      prevention effort in sub-Saharan Africa where a substantial proportion of HIV
      transmission occurs within stable partnerships. This study aimed to determine the
      acceptance and effectiveness of CVCT as compared to individual VCT (IVCT). 1,521
      women attending three antenatal clinics in Dar es Salaam were randomized to
      receive IVCT during that visit or CVCT with their husbands at a subsequent visit.
      The proportion of women receiving test results in the CVCT arm was significantly
      lower than in the IVCT arm (39 vs. 71%). HIV prevalence overall was 10%. In a
      subgroup analysis of HIV-positive women, those who received CVCT were more likely
      to use preventive measures against transmission (90 vs. 60%) and to receive
      nevirapine for themselves (55 vs. 24%) and their infants (55 vs. 22%) as compared
      to women randomized to IVCT. Uptake of CVCT is low in the antenatal clinic
      setting. Community mobilization and couple-friendly clinics are needed to promote
      CVCT.

PMID- 19763814
TI  - Correlates of past homelessness in the National Epidemiological Survey on Alcohol
      and Related Conditions.
AB  - This study sought to investigate correlates of past homelessness, especially
      mental illness and substance abuse, using data from the National epidemiological
      survey on alcohol and related conditions (NESARC), a large nationally
      representative survey conducted in 2001-2002. Multivariate analyses showed that
      the factors most strongly related to past homelessness were diagnoses of
      behavioral health conditions which showed consistently stronger association than
      sociodemographic characteristics, measures of economic well being, or general
      health indicators. The results presented here confirm in a nationally
      representative sample a number of single site studies that have also demonstrated
      the over representation of both mental illness and substance abuse disorders in
      homeless populations.

PMID- 19763815
TI  - The effect of induced mood on children's social information processing: goal
      clarification and response decision.
AB  - We investigated whether induced mood influenced the social information processing
      steps of goal clarification and response decision in 480 1st-3rd graders, and in
      more selected groups of low accepted-aggressive (n = 39), average accepted
      nonaggressive (n = 103), and high accepted-nonaggressive children (n = 68).
      Children participated in two sessions; in the first session peer assessments were
      administered. In the second session children were randomly assigned to receive
      either a happy, angry, or neutral mood induction prior to participating in a
      social cognitive interview assessing goals, outcome expectancies, and self
      efficacy for competent, hostile, and passive responses in the context of
      ambiguous provocations. Results revealed that an angry mood increased focus on
      instrumental goals. Low accepted-aggressive children were more susceptible to the
      effects of mood than were high accepted- and average-nonaggressive children. In
      addition, children's predominant goal orientation was related to children's
      response decisions; children with predominantly instrumental goals evaluated
      nonhostile responses to provocation more negatively and had higher self efficacy
      for hostile responses. Implications and future research directions are discussed.

PMID- 19763816
TI  - Interrelations between executive function and symptoms of
      hyperactivity/impulsivity and inattention in preschoolers: a two year
      longitudinal study.
AB  - The present study, including children at risk for developing Attention Deficit
      Hyperactivity Disorder (ADHD), examined the idea that complex executive functions
      (EFs) build upon more simple ones. This notion was applied in the study of
      longitudinal interrelations between core EF components - simple and complex
      inhibition, selective attention, and working memory (WM) - at age 5 and 6 as well
      as their predictive relations to ADHD symptoms at age 7. The results showed that
      simple inhibition and selective attention at age 5 independently predicted
      complex inhibition and WM at age 6. In addition, EFs primarily predicted symptoms
      of inattention rather than hyperactivity/impulsivity even at this young age.
      Finally, age 6 complex inhibition was shown to act as a mediator in the relations
      between simple inhibition and selective attention at age 5 and symptoms of
      inattention at age 7. These findings provide novel longitudinal support for the
      theory that fundamental EF components show a progression with age toward more
      complex executive control (see Garon et al. Psychological Bulletin 134(1):31-60
      2008). Further, complex inhibition, implicating both inhibition and WM, seems to
      be a particularly strong correlate of ADHD symptoms in young children and should
      as such be the focus of future studies examining the relation between cognitive
      function and ADHD symptoms from a developmental perspective.

PMID- 19763817
TI  - Four human breast cancer cell lines with biallelic inactivating alpha-catenin
      gene mutations.
AB  - Mutations of E-cadherin have been identified in half of lobular breast cancers
      and diffuse-type gastric cancers, two tumor subtypes with remarkably similar
      pathological appearances including small rounded cells with scant cytoplasm and a
      diffuse growth pattern. A causal role for E-cadherin gene mutations in the
      lobular breast cancer phenotype was recently demonstrated in E-cadherin knock-out
      mice. These observations suggested that another gene in the E-cadherin tumor
      suppressor pathway might be mutated in lobular breast cancers with wild-type E
      cadherin genes. Here, we identified E-cadherin gene mutations exclusively in
      human breast cancer cell lines that grow with a rounded cell morphology. Using
      expression analyses and gene mutation analyses, we have identified four biallelic
      inactivating alpha-catenin mutations among 55 human breast cancer cell lines. All
      four alpha-catenin mutations predicted premature termination of the encoded
      proteins, and concordantly, none of the four mutant cell lines expressed alpha
      catenin proteins. Importantly, three of the alpha-catenin mutant cell lines had
      the rounded cell morphology and all 14 cell lines with the rounded cell
      morphology had mutations of either E-cadherin or alpha-catenin. As anticipated,
      loss of alpha-catenin protein expression was associated with the lobular subtype
      in primary breast cancers. Together, our observations suggest that alpha-catenin
      may be a new tumor suppressor gene that operates in the E-cadherin tumor
      suppressor pathway.

PMID- 19763818
TI  - More radiotherapy for radiation-induced second malignancies?

PMID- 19763819
TI  - Evaluation of variants in the CHEK2, BRIP1 and PALB2 genes in an Irish breast
      cancer cohort.
AB  - It has been proposed that rare variants within the double strand break repair
      genes CHEK2, BRIP1 and PALB2 predispose to breast cancer. The aim of this study
      was to evaluate the prevalence of these variants in an Irish breast cancer cohort
      and determine their contribution to the development of breast cancer in the west
      of Ireland. We evaluated the presence of CHEK2_1100delC variant in 903 breast
      cancer cases and 1,016 controls. Six previously described variants within BRIP1
      and five within PALB2 were screened in 192 patients with early-onset or familial
      breast cancer. Where a variant was evident, it was then examined in the remainder
      of our 711 unselected breast cancer cases. CHEK2_1100delC was found in 5/903
      (0.5%) breast cancer cases compared to 1/1016 (0.1%) controls. One mutation at
      BRIP1 (2392 C>T) was identified in the early-onset/familial cohort. Examination
      of this variant in the remainder of our cohort (711 cases) failed to identify any
      additional cases. None of the previously described PALB2 variants were
      demonstrated in the early-onset/familial cohort. We show evidence of
      CHEK2_1100delC and BRIP1 2392 C>T within the Irish population. CHEK2_1100delC and
      BRIP1 mutations incidence in Ireland is similar to that found in other unselected
      breast cancer cohorts from northern European countries. We found no evidence to
      suggest that PALB2 mutation is an important breast cancer predisposition gene in
      this population.

PMID- 19763820
TI  - Adoptively transferred ex vivo expanded gammadelta-T cells mediate in vivo
      antitumor activity in preclinical mouse models of breast cancer.
AB  - In contrast to antigen-specific alphabeta-T cells (adaptive immune system),
      gammadelta-T cells can recognize and lyse malignantly transformed cells almost
      immediately upon encounter in a manner that does not require the recognition of
      tumor-specific antigens (innate immune system). Given the well-documented
      capacity of gammadelta-T cells to innately kill a variety of malignant cells,
      efforts are now actively underway to exploit the antitumor properties of
      gammadelta-T cells for clinical purposes. Here, we present for the first time
      preclinical in vivo mouse models of gammadelta-T cell-based immunotherapy
      directed against breast cancer. These studies were explicitly designed to
      approximate clinical situations in which adoptively transferred gammadelta-T
      cells would be employed therapeutically against breast cancer. Using radioisotope
      labeled gammadelta-T cells, we first show that adoptively transferred gammadelta
      T cells localize to breast tumors in a mouse model (4T1 mammary adenocarcinoma)
      of human breast cancer. Moreover, by using an antibody directed against the
      gammadelta-T cell receptor (TCR), we determined that localization of adoptively
      transferred gammadelta-T cells to tumor is a TCR-dependant process. Additionally,
      biodistribution studies revealed that adoptively transferred gammadelta-T cells
      traffic differently in tumor-bearing mice compared to healthy mice with fewer
      gammadelta-T cells localizing into the spleens of tumor-bearing mice. Finally, in
      both syngeneic (4T1) and xenogeneic (2Lmp) models of breast cancer, we
      demonstrate that adoptively transferred gammadelta-T cells are both effective
      against breast cancer and are otherwise well-tolerated by treated animals. These
      findings provide a strong preclinical rationale for using ex vivo expanded
      adoptively transferred gammadelta-T cells as a form of cell-based immunotherapy
      for the treatment of breast cancer. Additionally, these studies establish that
      clinically applicable methods for radiolabeling gammadelta-T cells allows for the
      tracking of adoptively transferred gammadelta-T cells in tumor-bearing hosts.

PMID- 19763822
TI  - Variation in plasma cholinesterase activity in the clay-colored robin (Turdus
      grayi) in relation to time of day, season, and diazinon exposure.
AB  - Cholinesterase (ChE) activity in birds is subject to interspecific and
      intraspecific species variations. Factors that influence enzyme activity have to
      be taken into account in order to obtain an accurate estimation of cholinesterase
      inhibition due to pesticide exposure in wild birds. This study evaluates
      variation of plasma cholinesterase activity in clay-colored robin (Turdus grayi)
      in relation to time of day, season, and exposure to diazinon. Other variables
      that can affect cholinesterase activity such as weight are also taken into
      account. The birds were marked, weighed and sexed using the cloacal technique.
      One dose of commercial diazinon mixed with papaya was fed to each bird at
      concentrations of 0.0, 0.5, 1.5 and 3.0 mg/kg ai. The results showed differences
      in ChE activity between seasons (t = -3.07, P < 0.05). Also, diurnal plasma
      cholinesterase variations were observed (20% in 2 h). The highest inhibition
      values were 73% for birds dosed with 1.5 mg/kg ai. Our study provides field and
      laboratory data on variation of ChE activity in a tropical bird species.
      Knowledge of the variation of ChE in the clay-colored robin will enable us to use
      this species as an indicator of exposure to ChE inhibiting pesticides in tropical
      agroecosystems.

PMID- 19763823
TI  - Antidepressant adequacy and work status among medicaid enrollees with
      disabilities: a restriction-based, propensity score-adjusted analysis.
AB  - Abstract This cross-sectional study of adult survey respondents with disability
      and depression (n = 199) enrolled in Massachusetts' Medicaid program examined the
      association of adequately or inadequately prescribed antidepressant treatment and
      self-reported work status using conditional logistic regression, controlling for
      age, gender, race, marital status, education, receipt of SSI/SSDI, self-reported
      disabling condition, and health status. Confounding by severity was addressed by
      two methods: restriction of our sample and subsequent stratification by
      propensity score. Individuals receiving adequate antidepressant treatment had an
      increased odds of working compared to individuals receiving inadequate treatment,
      both in analyses in which restriction was used to limit confounding (OR = 3.45,
      95% CI = 1.15-10.32, P < .03), and in analyses which combined restriction with
      adjustment by propensity score stratification (OR = 3.04, 95% CI = 1.01-9.62, P <
      .05). Among this sample of Medicaid enrollees with disability and depression,
      those receiving adequate antidepressant treatment were significantly more likely
      to report working.

PMID- 19763821
TI  - Potential of endothelin-1 and vasopressin antagonists for the treatment of
      congestive heart failure.
AB  - It is now becoming clear that two major systems namely the sympathetic nervous
      system and the renin-angiotensin system are activated in response to ischemic
      injury; these result in the elevation of plasma catecholamines and angiotensin II
      during the development of myocardial infarction as well as congestive heart
      failure. Although plasma levels of several other hormones including aldosterone,
      endothelin, vasopressin, natriuretic peptides, growth factors and inflammatory
      cytokines are also increased in heart failure, their relationship with changes in
      catecholamine and/or angiotensin levels as well as their significance for the
      induction of congestive heart failure are poorly understood. In this article we
      have examined the evidence regarding the role of endothelin and vasopressin in
      the pathogenesis of cardiac hypertrophy and congestive heart failure in addition
      to evaluating the significance of their antagonism by using their receptor
      blockade for treatment of congestive heart failure. Endothelin appears to
      maintain blood pressure by its vasoconstricting action whereas vasopressin
      primarily produces similar effect by retention of body fluid. Myocardium is also
      known to express both ET-A and ET-B receptors in addition to V1 and V2 receptors
      for vasopressin, which have been shown to induce cardiac remodeling. Out of
      various ET-1 receptor antagonists, which are available, a non-selective
      endothelin receptor antagonist, bosentan, as well as an ET-A receptor antagonist,
      BQ-123, seem most promising for the treatment of congestive heart failure.
      Likewise, vasopressin antagonists such as a non-selective antagonist, conivaptan,
      as well as V2 selective antagonist, tolvaptan, may prove highly valuable for the
      therapy of this condition. Since most of the existing interventions are helpful
      in treating patients with congestive heart failure only partially, there appears
      to be a real challenge for developing some combination therapy for the treatment
      of congestive heart failure.

PMID- 19763824
TI  - Glutathione S-transferase M1 null genotype associated with gastric cancer among
      Asians.
AB  - PURPOSE: The Glutathione S-transferases (GSTs) play multiple roles in the
      pathogenesis and treatment of cancer. Studies investigating the association
      between Glutathione S-transferase M1 (GSTM1) null genotype and gastric cancer
      risk report conflicting results. The purpose of this study was to quantitatively
      summarize the evidence for such a relationship. RESULTS: This meta-analysis
      included 35 studies, which included 4,505 gastric cancer cases and 9,062
      controls. The combined results based on all studies showed that the GSTM1 null
      genotype was associated with an increased risk of gastric cancer (OR = 1.15, 95%
      confidence interval [CI] = 1.02, 1.29). When stratifying for race, results were
      similar among Asians (OR = 1.24, 95% CI = 1.07, 1.44) except Caucasians (OR =
      1.04, 95% CI = 0.88, 1.24). When stratifying by the location, stage, Lauren's
      classification, histological differentiation, lymph node metastasis, smoking, and
      Helicobacter pylori infection of gastric cancer, we observed that patients with
      diffuse classification had a significantly higher frequency null genotype (OR =
      4.80, 95% CI = 1.65,13.94) than those with intestinal classification among
      Caucasians. CONCLUSIONS: This meta-analysis suggests that the GSTM1 null genotype
      may be associated with gastric cancer among Asians.

PMID- 19763826
TI  - Irregular changes in the structure of flowing blood at low flow conditions.
AB  - The structural organization of the dispersed phase of blood was studied by
      measuring the conductance (G) and the capacitance (C) of red blood cell (RBC)
      suspensions flowing in a vertical channel. Steady-state C and G signals exhibit
      erratic fluctuations around mean values; the root mean square of the fluctuating
      signals decreases rapidly as the average flow rate (<upsilon>) increases from
      0.21 to ~4.17 mm/s and then less rapidly at higher velocities. The intensity of
      oscillations is substantially reduced for suspensions with weaker aggregating
      media. Analysis of the fluctuations performed in the framework of the equivalent
      electrical circuits for flowing blood gives rise to the following conclusions:
      (1) Instantaneous hematocrit (Hct) and velocity cross-stream profiles are non
      smooth functions of radial position. (2) Oscillations of conductance at low flow
      conditions reflect irregular changes in the RBC network structure caused by
      fluctuations of aggregation-disaggregation equilibrium in the non-uniform shear
      field. (3) A transformation of the rheological behavior of RBC suspensions from
      shear-thinning to shear-thickening in a low flow regime amplifies fluctuations of
      aggregation-disaggregation equilibrium.

PMID- 19763825
TI  - Characteristics and trends in the incidence of inflammatory bowel disease in
      Korean children: a single-center experience.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) is rare in Asian children and few
      reports on pediatric IBD have appeared. AIMS: We, therefore, investigated the
      incidence trends and clinical characteristics of pediatric IBD in Korea. METHODS:
      We enrolled 48 children with Crohn's disease (CD) and 14 children with ulcerative
      colitis (UC) from 1996 to 2007. Trends in annual enrollment and clinical
      characteristics were retrospectively evaluated by medical record review. RESULTS:
      During the 12 years of observation, the number of new enrollments gradually
      increased. CD showed male predominance (33 boys, 15 girls), but more females
      presented with UC (4 boys, 10 girls). A relevant family history was observed in 3
      (4.9%) of the 61 unrelated families. The most common presenting symptom was
      abdominal pain (67%) in CD and hematochezia (93%) in UC. Growth delay was
      observed in 10% of CD patients, but not in any of the UC patients. In CD, colonic
      involvement occurred in 87% of patients, ileal involvement in 87%, and both the
      small bowel and colon were affected in 75%. With UC, pancolitis occurred in 43%
      of patients, left-sided colitis in 36%, and proctitis in 21%, including all three
      patients with appendiceal orifice inflammation. The most frequent disease
      behavior was inflammatory in 85% of patients, but perianal fistula was noted in
      50% of CD patients. CONCLUSION: This study showed that the incidence of pediatric
      IBD has been rapidly increasing in Korea in recent years. Relevant family history
      is less prevalent and phenotypic expression differs from what is seen in Western
      countries.

PMID- 19763827
TI  - Differences in the crack resistance of interstitial, osteonal and trabecular bone
      tissue.
AB  - The purpose of this work was to investigate differences which may exist in the
      crack resistance of the microstructural bone tissues, i.e., osteonal,
      interstitial and trabecular bone. Indentations, using varying loads were used to
      initiate cracks of the same size scale as those which exist habitually in bone.
      The crack lengths and corresponding toughness values are presented for each of
      the tissues. Specimens were prepared using standard nanoindentation preparation
      techniques. Young's modulus and hardness were measured using a Berkovich tip,
      while cracks were produced using a cube-corner tip. Crack lengths were
      subsequently measured using scanning electron microscopy. Cracks produced at the
      same loads were significantly longer in trabecular bone than in interstitial and
      osteonal cortical bone. Similarly, within individual subjects, cracks produced in
      interstitial bone were longer than those produced in osteonal bone. These results
      provide significant experimental evidence that bone microstructural tissues
      exhibit differing resistance to crack growth and may help explain the incidence
      of more microcracks in interstitial than osteonal bone. The ability of the
      technique to distinguish differences between individual bone tissues is promising
      in an area where the focus has switched to the microscale, and in particular, to
      measures bone quality.

PMID- 19763828
TI  - Modulation of ATP/ADP concentration at the endothelial cell surface by flow:
      effect of cell topography.
AB  - Determining how flow affects the concentration of the adenine nucleotides ATP and
      ADP at the vascular endothelial cell (EC) surface is essential for understanding
      flow-induced mobilization of intracellular calcium. Previously, mathematical
      models were formulated to describe the ATP/ADP concentration at the EC surface;
      however, all previous models assumed the endothelium to be flat. In the present
      study we investigate the effect of surface undulations on ATP/ADP concentration
      at the EC surface. The results demonstrate that under certain geometric and flow
      conditions, the ATP + ADP concentration at the EC surface is considerably lower
      for a wavy cell surface than for a flat surface. Because ECs in regions of
      disturbed arterial flow are expected to have larger undulations than cells in non
      disturbed flow zones, our findings suggest that ECs in regions of flow
      disturbance would exhibit lower ATP + ADP concentrations at their surfaces, which
      may lead to impaired calcium signaling. If validated experimentally, the present
      results may contribute to our understanding of endothelial cell dysfunction
      observed in regions of disturbed flow.

PMID- 19763829
TI  - Relationships between total and non-recoverable strain fields in glenohumeral
      capsule during shoulder subluxation.
AB  - Non-recoverable strain in the glenohumeral capsule is of prime clinical
      significance, but the factors that contribute to non-recoverable strain are
      largely unknown. This study examined the relationship between total and non
      recoverable strain in the antero-inferior glenohumeral capsule using an
      experimental model. Maximum principal total strain alone explained up to 35% of
      the variance in non-recoverable strain. A multiple regression model, including
      variables for lateral position and specimen, explained 50% of the variance in non
      recoverable strain. Both linear and quadratic terms for maximum principal total
      strain were significant predictors of non-recoverable strain. The correlation of
      total and non-recoverable strain directions exhibited a slope of nearly 1:1. The
      regression model showed that non-recoverable strain is likely to be low for small
      levels of total strain, and increase non-linearly with total strain. Non
      recoverable strain tended to be higher closer to the glenoid, even when
      controlling for total strain. Minimum principal total strain was not a
      significant predictor of non-recoverable strain for the cases examined,
      indicating that the glenohumeral capsule may demonstrate uniaxial failure
      behavior even when loaded biaxially. These results are important toward
      prediction of non-recoverable strain in computational models of glenohumeral
      subluxation, as well as for theoretical models of ligament failure.

PMID- 19763830
TI  - Myofiber ellipticity as an explanation for transverse asymmetry of skeletal
      muscle diffusion MRI in vivo signal.
AB  - Due to its unique non-invasive microstructure probing capabilities, diffusion
      tensor imaging (DTI) constitutes a valuable tool in the study of fiber
      orientation in skeletal muscles. By implementing a DTI sequence with judiciously
      chosen directional encoding to quantify in vivo the microarchitectural properties
      in the calf muscles of three healthy volunteers at rest, we report that the
      secondary eigenvalue is significantly higher than the tertiary eigenvalue, a
      phenomenon corroborated by prior DTI findings. Toward a physics-based explanation
      of this phenomenon, we propose a composite medium model that accounts for water
      diffusion in the space within the muscle fiber and the extracellular space. The
      muscle fibers are abstracted as cylinders of infinite length with an elliptical
      cross section, the latter closely approximating microstructural features well
      documented in prior histological studies of excised muscle. The range of values
      of fiber ellipticity predicted by our model agrees with these studies, and the
      spatial orientation of the cross-sectional ellipses is consistent with local
      muscle strain fields and the putative direction of lateral transmission of stress
      between fibers in certain regions in three antigravity muscles (Tibialis
      Anterior, Soleus, and Gastrocnemius), as well as independent measurements of
      deformation in active calf muscles. As a metric, fiber cross-sectional
      ellipticity may be useful for quantifying morphological changes in skeletal
      muscle fibers with aging, hypertrophy, or sarcopenia.

PMID- 19763831
TI  - Prayer as therapeutic process toward transforming destructiveness within a
      spiritual direction relationship.
AB  - This article will expand previous conceptualizations (Kuchan, Presence Int J
      Spiritual Dir 12(4):22-34, 2006; J Religion Health 47(2):263-275, 2008; J
      Pastoral Care Counsel, forthcoming) of what might be occurring during a prayer
      practice that creates space within a spiritual direction relationship for the
      creation of inner images that reveal a person's unconscious relational longings
      and co-created representations of God that seem to facilitate therapeutic process
      toward aliveness. In previous articles, I suggest one way to understand the
      prayer experience is through a lens of Winnicottian notions of transitional
      space, illusion, and co-creation of God images. This article expands on these
      ideas to include an understanding of God as Objective Other (Lewis, The four
      loves, 1960) interacting with a part of a person's self (Jung, in: The structure
      and dynamics of the psyche, collected works 8, 1934; Symington, Narcissism, a new
      theory, 1993) that has capacity for subjectivity (Benjamin, Like subjects, love
      objects: Essays on recognition and sexual difference, 1995) and co-creation
      (Winnicott, Home is where we start from: Essays by a psychoanalyst, 1990), of
      inner representations of God (Ulanov, Winnicott, god and psychic reality, 2001).
      I also expand on a notion of God as "Source of aliveness" by integrating an
      aspect of how Symington (Narcissism, a new theory, 1993) thinks about "the
      lifegiver," which he understands to be a mental object. After offering this
      theoretical expansion of the prayer practice/experience, one woman's inner
      representations of self and God are reflected upon in terms of a therapeutic
      process toward transforming destructiveness, utilizing ideas from Winnicott,
      Kohut, and Benjamin.

PMID- 19763832
TI  - Improved antioxidant and anti-inflammatory potential in mice consuming sour
      cherry juice (Prunus Cerasus cv. Maraska).
AB  - The present investigation tested the in vivo antioxidant efficacy (superoxide
      dismutase, SOD; catalase, CAT; glutathione peroxidase; Gpx), lipid peroxidation
      (LPO) and anti-inflammatory properties (cyclooxygenase-2; COX-2) of sour cherry
      juices obtained from an autochthonous cultivar (Prunus cerasus cv. Maraska) that
      is grown in coastal parts of Croatia. Antioxidant potential was tested in mouse
      tissue (blood, liver, and brain), LPO (liver, brain) and anti-inflammatory
      properties in glycogen elicited macrophages. Additionally, the concentration of
      cyanidin-3-glucoside, cyanidin-3-rutinoside, pelargonidin-3-glucoside,
      pelargonidin-3-rutinoside and total anthocyanins present in Prunus cerasus cv.
      Maraska cherry juice was determined. Mice were randomly divided into a control
      group (fed with commercial food pellets) and 2 experimental groups (fed with
      commercial food pellets with 10% or 50% of cherry juice added). Among the
      anthocyanins, the cyanidin-3-glucoside was present in the highest concentration.
      These results show antioxidant action of cherry juice through increased SOD
      (liver, blood) and Gpx (liver) activity and decreased LPO concentration. The
      study highlights cherry juice as a potent COX-2 inhibitor and antioxidant in the
      liver and blood of mice, but not in the brain. Thus, according to our study,
      Prunus cerasus cv. Maraska cherry juice might potentially be used as an
      antioxidant and anti-inflammatory product with beneficial health-promoting
      properties.

PMID- 19763833
TI  - Nutrient content of carob pod (Ceratonia siliqua L.) flour prepared commercially
      and domestically.
AB  - Although the fruit of the carob tree (Ceratonia siliqua L. Fabaceae) is
      nutritious and widely available in Turkey, especially in West and South Anatolia,
      much remains to be learned about its nutrient composition. The main goal of our
      study was to determine if there are differences in the content of certain
      nutrients in commercially-prepared carob flour (CPCP) and domestic or home
      prepared carob powder (HPCP). Sucrose was the main sugar in CPCP and HPCP. Total
      protein was 40% lower in CPCP than HPCP due mainly to decreases in the content of
      several essential amino acids. However, except for lysine in CPCP, HPCP and CPCP
      compared favourably to a WHO protein standard. There were large differences in
      terms of their content of the two essential fatty acids, linoleic and alpha
      linolenic acid, and the linoleic acid/alpha-linolenic acid ratio was 3.6 for
      CPCP, and 6.1 for HPCP. Manganese and iron were 2.5-fold higher in HPCP than
      CPCP. This study demonstrates that carob flour prepared in either the household
      or industrially is a good source of many, but not all essential nutrients, and
      that commercial processing of carob fruit into flour seems to affect its content
      of several important nutrients.

PMID- 19763834
TI  - RoboSCell: an automated single cell arraying and analysis instrument.
AB  - Single cell research has the potential to revolutionize experimental methods in
      biomedical sciences and contribute to clinical practices. Recent studies suggest
      analysis of single cells reveals novel features of intracellular processes, cell
      to-cell interactions and cell structure. The methods of single cell analysis
      require mechanical resolution and accuracy that is not possible using
      conventional techniques. Robotic instruments and novel microdevices can achieve
      higher throughput and repeatability; however, the development of such
      instrumentation is a formidable task. A void exists in the state-of-the-art for
      automated analysis of single cells. With the increase in interest in single cell
      analyses in stem cell and cancer research the ability to facilitate higher
      throughput and repeatable procedures is necessary. In this paper, a high
      throughput, single cell microarray-based robotic instrument, called the
      RoboSCell, is described. The proposed instrument employs a partially transparent
      single cell microarray (SCM) integrated with a robotic biomanipulator for in
      vitro analyses of live single cells trapped at the array sites. Cells, labeled
      with immunomagnetic particles, are captured at the array sites by channeling
      magnetic fields through encapsulated permalloy channels in the SCM. The RoboSCell
      is capable of systematically scanning the captured cells temporarily immobilized
      at the array sites and using optical methods to repeatedly measure extracellular
      and intracellular characteristics over time. The instrument's capabilities are
      demonstrated by arraying human T lymphocytes and measuring the uptake dynamics of
      calcein acetoxymethylester--all in a fully automated fashion.

PMID- 19763835
TI  - Microglia in central nervous system diseases.

PMID- 19763836
TI  - Quality of life following incontinent cutaneous and orthotopic urinary
      diversions.
AB  - The quality of life (QOL) of patients requiring urinary diversion remains an
      important issue within the field of Urology. The majority of this population has
      undergone cystectomy as treatment for malignant disease. In the initial phases of
      treatment counseling, the patient is focused on the eradication of their tumor.
      However, it is the urinary diversion that will have a lasting functional impact
      on the patient every day for the rest of their lives. The selection of an
      appropriate diversion, then, is critical to long-term satisfaction with the
      surgical treatment. Patients must be fully counseled in all types of urinary
      diversion and should have ready access to all options. Reported differences in
      QOL between diversion populations are difficult to interpret in view of
      limitations in the methodology of study designs and apparent selection bias.
      Ultimately, as a community, urologists cannot definitively say that one class of
      urinary diversion is superior to another. Instead, we must empower the patient in
      their own decision making with an accurate impression of diversion recovery,
      required education and training, and related side-effects and complications. The
      choice of urinary diversion still remains a very personal decision to be made
      between the patient, family members, friends, and the physician.

PMID- 19763837
TI  - Evaluation of Mimosa pudica seed mucilage as sustained-release excipient.
AB  - The present study was conducted to investigate the sustained-release properties
      of Mimosa pudica seed mucilage. Matrix tablets of diclofenac sodium containing
      different proportions of mucilage and dibasic calcium phosphate as diluent were
      formulated by wet granulation method. The tablets had uniform physical
      appearance, average weight, drug content, and adequate hardness. The results of
      in vitro release conducted using USP type II dissolution rate apparatus, in a
      dissolution media comprising of 900 mL of 0.1 N HCl for 2 h followed by phosphate
      buffer (pH 6.8) for 24 h at 37 degrees C and 50 rpm, revealed that as the
      proportion of mucilage in the matrix was increased there was a corresponding
      decrease in the release of drug. Further, the matrix tablets were found to
      release the drug following Higuchi square root release kinetics, with the
      mechanism of release being diffusion for tablets containing higher proportion of
      mucilage and a combination of matrix erosion and diffusion for tablets containing
      smaller proportion of mucilage. The swelling and erosion studies revealed that,
      as the proportion of mucilage in tablets was increased, there was a corresponding
      increase in percent swelling and a decrease in percent erosion of tablets. The
      SEM photomicrographs showed gelling structures in tablets containing higher
      percentage of mucilage, while both pores and gelling structures were present on
      the surface of tablets containing smaller proportion of mucilage and commercial
      formulation. On comparative evaluation, the dissolution profile from formulation
      containing mucilage to drug in the proportion of 1:40 was found to be similar to
      the commercial sustained-release formulation of diclofenac.

PMID- 19763838
TI  - Ethyl cellulose microcapsules for protecting and controlled release of folic
      acid.
AB  - Ethyl cellulose microcapsules were developed for use as a drug-delivery device
      for protecting folic acid from release and degradation in the undesirable
      environmental conditions of the stomach, whilst allowing its release in the
      intestinal tract to make it available for absorption. The controlled release
      folic acid-loaded ethyl cellulose microcapsules were prepared by oil-in-oil
      emulsion solvent evaporation using a mixed solvent system, consisting of a 9:1
      (v/v) ratio of acetone:methanol and light liquid paraffin as the dispersed and
      continuous phase. Span 80 was used as the surfactant to stabilize the emulsion.
      Scanning electron microscopy revealed that the microcapsules had a spherical
      shape. However, the particulate properties and in vitro release profile depended
      on the concentrations of the ethyl cellulose, Span 80 emulsifier, sucrose (pore
      inducer), and folic acid. The average diameter of the microcapsules increased
      from 300 to 448 microm, whilst the folic acid release rate decreased from 52% to
      40%, as the ethyl cellulose concentration was increased from 2.5% to 7.5% (w/v).
      Increasing the Span 80 concentration from 1% to 4% (v/v) decreased the average
      diameter of microcapsules from 300 to 141 microm and increased the folic acid
      release rate from 52% to 79%. The addition of 2.5-7.5% (w/v) of sucrose improved
      the folic acid release from the microcapsules. The entrapment efficiency was
      improved from 64% to 88% when the initial folic acid concentration was increased
      from 1 to 3 mg/ml.

PMID- 19763839
TI  - Multivariate data analysis as a semi-quantitative tool for interpretive
      evaluation of comparability or equivalence of aerodynamic particle size
      distribution profiles.
AB  - The purpose of this article is to investigate the performance of multivariate
      data analysis, especially orthogonal partial least square (OPLS) analysis, as a
      semi-quantitative tool to evaluate the comparability or equivalence of
      aerodynamic particle size distribution (APSD) profiles of orally inhaled and
      nasal drug products (OINDP). Monte Carlo simulation was employed to reconstitute
      APSD profiles based on 55 realistic scenarios proposed by the Product Quality
      Research Institute (PQRI) working group. OPLS analyses with different data
      pretreatment methods were performed on each of the reconstituted profiles.
      Compared to unit-variance scaling, equivalence determined based on OPLS analysis
      with Pareto scaling was shown to be more consistent with the working group
      assessment. Chi-square statistics was employed to compare the performance of OPLS
      analysis (Pareto scaling) with that of the combination test (i.e., chi-square
      ratio statistics and population bioequivalence test for impactor-sized mass) in
      terms of achieving greater consistency with the working group evaluation. A p
      value of 0.036 suggested that OPLS analysis with Pareto scaling may be more
      predictive than the combination test with respect to consistency. Furthermore,
      OPLS analysis may also be employed to analyze part of the APSD profiles that
      contribute to the calculation of the mass median aerodynamic diameter. Our
      results show that OPLS analysis performed on partial deposition sites do not
      interfere with the performance on all deposition sites.

PMID- 19763840
TI  - Evaluation of agile designs in first-in-human (FIH) trials--a simulation study.
AB  - The aim of the investigation was to evaluate alternatives to standard first-in
      human (FIH) designs in order to optimize the information gained from such studies
      by employing novel agile trial designs. Agile designs combine adaptive and
      flexible elements to enable optimized use of prior information either before
      and/or during conduct of the study to seamlessly update the study design. A
      comparison of the traditional 6 + 2 (active + placebo) subjects per cohort design
      with alternative, reduced sample size, agile designs was performed by using
      discrete event simulation. Agile designs were evaluated for specific adverse
      event models and rates as well as dose-proportional, saturated, and steep
      accumulation pharmacokinetic profiles. Alternative, reduced sample size
      (hereafter referred to as agile) designs are proposed for cases where prior
      knowledge about pharmacokinetics and/or adverse event relationships are available
      or appropriately assumed. Additionally, preferred alternatives are proposed for a
      general case when prior knowledge is limited or unavailable. Within the tested
      conditions and stated assumptions, some agile designs were found to be as
      efficient as traditional designs. Thus, simulations demonstrated that the agile
      design is a robust and feasible approach to FIH clinical trials, with no
      meaningful loss of relevant information, as it relates to PK and AE assumptions.
      In some circumstances, applying agile designs may decrease the duration and
      resources required for Phase I studies, increasing the efficiency of early
      clinical development. We highlight the value and importance of useful prior
      information when specifying key assumptions related to safety, tolerability, and
      PK.

PMID- 19763841
TI  - Emotion, stress, and cardiovascular response: an experimental test of models of
      positive and negative affect.
AB  - BACKGROUND: The nature of the relationship between positive affect (PA) and
      negative affect (NA) has been a topic of debate for some time. In particular,
      there are gaps in our knowledge of the independent effects of PA and NA on health
      under stress. PURPOSE: The study examined the effects of a laboratory-induced
      stressor on the experience of PA and NA, and the effects of affect on
      cardiovascular (CV) reactivity and recovery. METHOD: A sample of 56 female
      college students was randomly assigned to a public speaking (stress) task or a
      silent reading (control) task. Pre- and posttask PA and NA were measured using
      the Positive and Negative Affect Schedule (PANAS Watson J Pers Soc Psychol
      54:1,063-1,070, 1988). Baseline, task, and posttask cardiovascular measures were
      also recorded. RESULTS: The results indicated that PA and NA responded
      differently to the stressor and contributed independently to the prediction of
      both CV reactivity and recovery. Of particular interest was the finding that
      higher levels of both PA and NA predicted greater CV recovery. CONCLUSION:
      Results are discussed in light of the debate concerning the (in)dependence of
      positive and negative emotions and the importance of understanding the dynamics
      of emotions, stress, and health.

PMID- 19763842
TI  - Do healthy people worry? Modern health worries, subjective health complaints,
      perceived health, and health care utilization.
AB  - BACKGROUND: Modern health worries (MHW) are concerns related to modern or
      technological features of daily life (e.g., air pollution, x-rays, food
      additives, etc.), and have been associated with subjective health complaints
      (SHC) and health care use. PURPOSE: The MHW scale was expected to predict aspects
      of health status in healthy individuals (e.g., health care visits, health
      perceptions, and medication use). SHC was thought to mediate the relationship
      between MHW and health care use. Likewise, negative affect was considered to
      mediate the relationship between MHW and SHC. METHOD: University students (n =
      432) completed assessments for MHW, SHC, perceptions of health, medication use,
      and health care visits. RESULTS: MHW were positively related to the number of
      subjective health complaints with negative affect partially driving this
      relationship. MHW were negatively related to reports of present health and
      medication use. MHW were marginally related, whereas SHC were significantly
      associated with health care utilization. CONCLUSION: Concerns over modern
      technology appear to influence symptom reporting, perceptions of current health,
      medication use, and, to a degree, visits to health care providers even in young
      healthy samples.

PMID- 19763843
TI  - Expression of vacuolar H+-pyrophosphatase (OVP3) is under control of an anoxia
      inducible promoter in rice.
AB  - Vacuolar H(+)-pyrophosphatase (V-PPase) expression increases in a number of
      abiotic stresses and is thought to play a role in adaptation to abiotic stresses.
      This paper reports on the regulation of six V-PPase genes in rice (Oryza sativa
      L.) coleoptiles under anoxia, using flood tolerant and intolerant cultivars to
      test our hypothesis. Quantitative PCR analysis showed that one vacuolar H(+)
      pyrophosphatase (OVP3) was induced by anoxia, particularly in flood-tolerant
      rice. Regulation of OVP3 expression under anoxia was investigated by analysing
      putative OVP promoters. The putative OVP3 promoter contained more previously
      identified anoxia-inducible motifs than the putative promoters of the other five
      OVP genes. GUS activity in transgenic rice plants containing the OVP3 promoter
      region linked to the GUS reporter gene was induced only by anoxia. Salt and cold
      treatments had little effect on OVP3 promoter-driven GUS expression when compared
      to the anoxic treatment.

PMID- 19763844
TI  - A transposon toolkit for gene transfer and mutagenesis in protozoan parasites.
AB  - Protozoan parasites affect millions of people around the world. Treatment and
      control of these diseases are complicated partly due to the intricate biology of
      these organisms. The interactions of species of Plasmodium, Leishmania and
      trypanosomes with their hosts are mediated by an unusual control of gene
      expression that is not fully understood. The availability of the genome sequence
      of these protozoa sets the stage for using more comprehensive, genome-wide
      strategies to study gene function. Transposons are effective tools for the
      systematic introduction of genetic alterations and different transposition
      systems have been adapted to study gene function in these human pathogens. A
      mariner transposon toolkit for use in vivo or in vitro in Leishmania parasites
      has been developed and can be used in a variety of applications. These modified
      mariner elements not only permit the inactivation of genes, but also mediate the
      rescue of translational gene fusions, bringing a major contribution to the
      investigation of Leishmania gene function. The piggyBac and Tn5 transposons have
      also been shown to mobilize across Plasmodium spp. genomes circumventing the
      current limitations in the genetic manipulation of these organisms.

PMID- 19763846
TI  - Reduction of bromate by biogenic sulfide produced during microbial sulfur
      disproportionation.
AB  - Bromate (BrO(3) (-)) is a carcinogenic contaminant formed during ozonation of
      waters that contain trace amounts of bromide. Previous research shows that
      bromate can be microbially reduced to bromide using organic (i.e. acetate,
      glucose, ethanol) and inorganic (H(2)) electron-donating substrates. In this
      study, the reduction of bromate by a mixed microbial culture was investigated
      using elemental sulfur (S(0)) as an electron donor. In batch bioassays performed
      at 30 degrees C, bromate (0.30 mM) was completely converted to bromide after 10
      days and no accumulation of intermediates occurred. Bromate was also reduced in
      cultures supplemented with thiosulfate and hydrogen sulfide as electron donor.
      Our results demonstrated that S(0)-disproportionating microorganisms were
      responsible for the reduction of bromate in cultures spiked with S(0) through an
      indirect mechanism involving microbial formation of sulfide and subsequent
      abiotic reduction of bromate by the biogenic sulfide. Confirmation of this
      mechanism is the fact that bromate was shown to undergo rapid chemical reduction
      by sulfide (but not S(0) or thiosulfate) in abiotic experiments. Bromate
      concentrations above 0.30 mM inhibited sulfide formation by S(0)
      disproportionating bacteria, leading to a decrease in the rate of bromate
      reduction. The results suggest that biological formation of sulfide from by S(0)
      disproportionation could support the chemical removal of bromate without having
      to directly use sulfide as a reagent.

PMID- 19763845
TI  - Nature as a source of inspiration for cationic lipid synthesis.
AB  - Synthetic gene delivery systems represent an attractive alternative to viral
      vectors for DNA transfection. Cationic lipids are one of the most widely used non
      viral vectors for the delivery of DNA into cultured cells and are easily
      synthesized, leading to a large variety of well-characterized molecules. This
      review discusses strategies for the design of efficient cationic lipids that
      overcome the critical barriers of in vitro transfection. A particular focus is
      placed on natural hydrophilic headgroups and lipophilic tails that have been used
      to synthesize biocompatible and non-toxic cationic lipids. We also present
      chemical features that have been investigated to enhance the transfection
      efficiency of cationic lipids by promoting the escape of lipoplexes from the
      endosomal compartment and DNA release from DNA-liposome complexes. Transfection
      efficiency studies using these strategies are likely to improve the understanding
      of the mechanism of cationic lipid-mediated gene delivery and to help the
      rational design of novel cationic lipids.

PMID- 19763847
TI  - Four marine-derived fungi for bioremediation of raw textile mill effluents.
AB  - Textile dye effluents pose environmental hazards because of color and toxicity.
      Bioremediation of these has been widely attempted. However, their widely
      differing characteristics and high salt contents have required application of
      different microorganisms and high dilutions. We report here decolorization and
      detoxification of two raw textile effluents, with extreme variations in their pH
      and dye composition, used at 20-90% concentrations by each of the four marine
      derived fungi. Textile effluent A (TEA) contained an azo dye and had a pH of 8.9
      and textile effluent B (TEB) with a pH of 2.5 contained a mixture of eight
      reactive dyes. The fungi isolated from mangroves and identified by 18S and ITS
      sequencing corresponded to two ascomycetes and two basidiomycetes. Each of these
      fungi decolorized TEA by 30-60% and TEB by 33-80% used at 20-90% concentrations
      and salinity of 15 ppt within 6 days. This was accompanied by two to threefold
      reduction in toxicity as measured by LC(50) values against Artemia larvae and 70
      80% reduction in chemical oxygen demand and total phenolics. Mass spectrometric
      scan of effluents after fungal treatment revealed degradation of most of the
      components. The ascomycetes appeared to remove color primarily by adsorption,
      whereas laccase played a major role in decolorization by basidiomycetes. A
      process consisting of a combination of sorption by fungal biomass of an
      ascomycete and biodegradation by laccase from a basidiomycete was used in two
      separate steps or simultaneously for bioremediation of these two effluents.

PMID- 19763848
TI  - Pollen consumption by flower mites in three  hummingbird-pollinated plant
      species.
AB  - Laboratory studies suggest that pollen consumption by flower mites may decrease
      the male fitness of the plant by reducing the available pollen for dispersal.
      Here we assessed pollen consumption by flower mites under natural conditions in
      three plant species with long-lived, protandrous flowers, Moussonia deppeana
      (Gesneriaceae), Lobelia laxiflora and L. cardinalis (Lobeliaceae). Total pollen
      mass was measured after 24 and 48 h in flowers exposed to flower mites and
      excluded from hummingbirds, flowers exposed to mites and hummingbird visitation,
      and in flowers recently opened with dehisced anthers. Compared with recently
      opened flowers, pollen availability was reduced about half in the presence of
      flower mites and the same effect was observed in the three plant species. Our
      results suggest that flower mites are removing a great deal of pollen and the
      reduction of pollen implies the possibility of direct impact on pollen transfer.

PMID- 19763849
TI  - Effects of adjuvant and conidial concentration on the efficacy of Beauveria
      bassiana for the control of the two spotted spider mite, Tetranychus urticae.
AB  - Greenhouse experiments were conducted on various crops (cucumber, tomato,
      eggplant, green bean) to ascertain the effects of Break-thru (polyether
      polymethylsiloxane-copolymer, a silicone surfactant) and an oil emulsion, on
      Beauveria bassiana (Balsamo) Vuillemin (Bb) applications for the control of the
      two spotted spider mite, Tetranychus urticae Koch. The objectives were to compare
      a) the efficacy of Bb control when applied in aqueous Break-thru or an oil
      emulsion; b) the effects of various concentrations of Bb conidia, as affected by
      each surfactant; and c) the effects of Break-thru on the activity of the fungus.
      Conidia were suspended either in an aqueous Break-thru or an emulsifiable
      formulation at different conidial concentrations (1.05 x 10(6), 2.1 x 10(6) and
      4.2 x 10(6) conidia ml(-1)) and sprayed onto leaves 2 weeks after artificial pest
      inoculation. Two sprays were performed, with an interval of one week from one
      spray to another, and T. urticae population counts (both motile and egg stages)
      were made on plant leaves 7 days after each spray. Bb conidia in Break-thru((R))
      were more efficacious than conidia in emulsifiable formulation. With the highest
      rate of conidia (4.2 x 10(6) conidia ml(-1)), mortality of adult mites ranged
      from 60 +/- 4.2 (mean +/- SE) to 85.7 +/- 4.3% in the Break-thru suspension and
      39.4 +/- 7 to 61.3 +/- 6% in the oil emulsion. Leaf damage index was also
      substantially reduced from 70% in the unsprayed control to 40% by the application
      of Bb conidia at the highest rate with Break-thru. Break-thru can be combined
      with Bb in the integrated management of T. urticae and Isolate R444 is a
      promising candidate for the control of the pest.

PMID- 19763850
TI  - Characterization of secophalloidin-induced force loss in cardiac myofibrils.
AB  - Secophalloidin (SPH) is known to cause in cardiac myofibrils force without Ca(2+)
      (half-maximal effect approximately 2 mM) followed by irreversible loss of Ca(2+)
      activated force. At maximal Ca(2+) activation, SPH increases force (half-maximal
      effect < 0.1 mM). We found that SPH at low concentration (0.5 mM) did not cause
      either force activation or force loss at pCa 8.7, but both of these effects did
      occur when force was activated by Ca(2+). The force loss was prevented when SPH
      was applied during rigor or in the presence of 2,3-butanedione monoxime (85 mM).
      Furthermore, studying muscle in which the force was previously reduced by SPH (up
      to 50%) did not reveal significant changes in Ca(2+) sensitivity and
      cooperativity of Ca(2+) activation or qualitative alterations in SPH-induced
      changes in Ca(2+)-activated contraction. Data suggest that the force loss is
      mediated by cycling cross-bridges, and might reflect a reduction in force
      generated by individual cross-bridges.

PMID- 19763851
TI  - Precise regulation of transgene expression level and control of cell physiology.
AB  - The elucidation of biological processes is inevitably linked with cells. To study
      these processes in basic research and in applied disciplines, cells usually are
      genetically manipulated. For the generation of biological meaningful data, a
      precise control of the transgene expression level is highly desirable. As cells
      are complex biological systems, the establishment of cell lines with such a
      predictable and/or controllable expression pattern is challenging. We have
      developed several techniques to achieve this goal with reasonable efforts. (1)
      Site-specific integration [molecular cut and paste mechanism (MCaP)] allows the
      generation of cell lines stably expressing the gene of interest within 4 weeks.
      In addition, these cell lines are characterised by a high and stable expression
      of the transgene. (2) The modulation of the transgene level can be easily
      achieved through transcriptional regulation. We found that the setup of the
      expression cassettes dramatically influences their expression pattern. (3) Cells
      reflecting in vivo properties are of high interest for life sciences. We have
      developed a system for cell expansion, which retains relevant cellular
      properties. The system is based on transcriptional control of expansion genes.
      The employed switch is mediated through the tetracycline system and allows strict
      and reversible control of cell proliferation.

PMID- 19763852
TI  - Potential sites of triple-helical nucleic acid formation in chromosomes of
      Rhynchosciara (Diptera: Sciaridae) and Drosophila melanogaster.
AB  - Antibodies to specific nucleic acid conformations are amongst the methods that
      have allowed the study of non-canonical (Watson-Crick) DNA structures in higher
      organisms. In this work, the structural limitations for the immunological
      detection of DNA.RNA hybrid duplexes were examined using specific RNA
      homopolymers as probes for homopolymer polydeoxyadenylic acid
      (poly(dA)).polydeoxythymidylic acid (poly(dT))-rich regions of Rhynchosciara
      americana (Diptera: Sciaridae) chromosomes. Anti-DNA.RNA duplexes did not react
      with the complex formed between chromosomal poly(dA) and exogenous polyuridylic
      acid (poly(rU)). Additionally, poly(rU) prevented the detection of polyadenylic
      acid.poly(dT) hybrid duplexes preformed in situ. These results raised the
      possibility that three-stranded structures rather than duplexes were formed in
      chromosomal sites. To test this hypothesis, the specificity of antibodies to
      triple-helical nucleic acids was reassessed employing distinct nucleic acid
      configurations. These antibodies were raised to the poly(dA).poly(rU).poly(rU)
      complex and have been used here for the first time in immunocytochemistry. Anti
      triplex antibodies recognised the complex poly(dA).poly(rU).poly(rU) assembled
      with poly(rU) in poly(dA).poly(dT)-rich homopolymer regions of R. americana
      chromosomes. The antibodies could not detect short triplex stretches, suggesting
      the existence of constraints for triple-helix detection, probably related to
      triplex tract length. In addition, anti-poly(dA).poly(rU).poly(rU) antibodies
      reacted with the pericentric heterochromatin of RNase-treated polytene
      chromosomes of R. americana and Drosophila melanogaster. In apparent agreement
      with data obtained in cell types from other organisms, the results of this work
      suggest that significant triple-helix DNA extensions can be formed in pericentric
      regions of these species.

PMID- 19763853
TI  - Nuclear architecture of resting and LPS-stimulated porcine neutrophils by 3D
      FISH.
AB  - Neutrophils are essential components of the innate immune system due to their
      ability to kill and phagocytose invading microbes. They possess a lobulated
      nucleus and are capable of extensive and complex changes in response to bacterial
      stimulation. The aim of our study was to investigate whether the 3D nuclear
      organization of porcine neutrophils was modified upon stimulation. The
      organization of centromeres, telomeres, and chromosome territories (chromosomes
      2, 3, 7, 8, 12, 13, and 17) was studied on structurally preserved nuclei using 3D
      fluorescence in situ hybridization, confocal microscopy, and image analysis. By
      differential labeling of centromeres of acrocentric and
      metacentric/submetacentric chromosomes, we showed that centromeres associated to
      form chromocenters but did so preferentially between chromosomes with the same
      morphology. Upon activation, some of these chromocenters dispersed. Telomeres
      were also found to form clusters, but their number remained unchanged in
      lipopolysaccharide-stimulated neutrophils. The analysis of the position of
      chromocenters and telomere clusters showed a more internal location of the latter
      compared to the former. The analysis of chromosome territories revealed that
      homologs were distributed randomly among lobes whatever the cell's status. The
      volume of these territories was not proportional to chromosome length, and some
      chromosomes (chr 3, 12, 13, and 17) were more prone to decondensation when
      neutrophils were stimulated. Thus, our study demonstrated that activation of
      neutrophils resulted in several modifications of their nuclear architecture: a
      decrease in the number of non-acrocentric chromocenters and the decondensation of
      several chromosomes.

PMID- 19763854
TI  - Groundwater environmental capacity and its evaluation index.
AB  - To date, no unified and acknowledged definition or well-developed evaluation
      index system of groundwater environment capacity can be found in the academia at
      home or abroad. The article explores the meaning of water environment capacity,
      and analyzes the environmental effects caused by the exploitation of groundwater
      resources. This research defines groundwater environmental capacity as a critical
      value in terms of time and space, according to which the groundwater system
      responds to the external influences within certain goal constraint. On the basis
      of observing the principles of being scientific, dominant, measurable, and
      applicable, six level 1 evaluation indexes and 11 constraint factors are
      established. Taking Jinan spring region for a case study, this research will
      adopt groundwater level and spring flow as constraint factors, and the allowable
      groundwater yield as the critical value of groundwater environmental capacity,
      prove the dynamic changeability and its indicating function of groundwater
      environmental capacity through calculation, and finally point out the development
      trends of researches on groundwater environmental capacity.

PMID- 19763855
TI  - Are multiple choice tests fair to medical students with specific learning
      disabilities?
AB  - The purpose of multiple choice tests of medical knowledge is to estimate as
      accurately as possible a candidate's level of knowledge. However, concern is
      sometimes expressed that multiple choice tests may also discriminate in
      undesirable and irrelevant ways, such as between minority ethnic groups or by sex
      of candidates. There is little literature to establish whether multiple choice
      tests may also discriminate against students with specific learning disabilities
      (SLDs), in particular those with a diagnosis of dyslexia, and whether the
      commonly-used accommodations allow such students to perform up to their
      capability. We looked for evidence to help us determine whether multiple choice
      tests could be relied upon to test all medical students fairly, regardless of
      disability. We analyzed the mean scores of over 900 undergraduate medical
      students on eight multiple-choice progress tests containing 1,000 items using a
      repeated-measures analysis of variance. We included disability, gender and
      ethnicity as possible explanatory factors, as well as year group. There was no
      significant difference between mean scores of students with an SLD who had test
      accommodations and students with no SLD and no test accommodation. Virtually all
      students were able to complete the tests within the allowed time. There were no
      significant differences between the mean scores of known minority ethnic groups
      or between the genders. We conclude that properly-designed multiple-choice tests
      of medical knowledge do not systematically discriminate against medical students
      with specific learning disabilities.

PMID- 19763856
TI  - Cognitive elements in clinical decision-making: toward a cognitive model for
      medical education and understanding clinical reasoning.
AB  - Physician cognition, metacognition and affect may have an impact upon the quality
      of clinical reasoning. The purpose of this study was to examine the relationship
      between measures of physician metacognition and affect and patient outcomes in
      obstetric practice. Reflective coping (RC), proactive coping, need for cognition
      (NFC), tolerance for ambiguity, state-trait anxiety and metacognitive awareness
      were assessed for obstetricians (n = 12) who provided intra-partum care to 4,149
      women. Outcome measures included delivery mode and intrapartum asphyxia. Analysis
      was carried out using logistic regression and tree-based classification.
      Obstetricians with high RC scores were more likely to perform a caesarean section
      (OR 1.59, p < 0.0001), less likely undertake a mid-forceps or low forceps
      delivery (OR 0.41, p < 0.0001; OR 0.49, p < 0.0001), and more likely to supervise
      a spontaneous vaginal delivery (OR 1.17, p = 0.08). Obstetricians with high NFC
      scores were more likely to perform a caesarean section (OR 1.53, p = 0.03), more
      likely to undertake a vacuum delivery (OR 5.8, p = 0.001), less likely undertake
      a mid-forceps delivery (OR 0.45, p = 0.02) and less likely to supervise a
      spontaneous vaginal delivery (OR 0.47, p < 0.0001). Obstetricians high in trait
      anxiety were more likely to perform a mid forceps delivery (OR 2.49, p = 0.01) or
      a vacuum delivery (OR 5.08, p = 0.003), and less likely to supervise a
      spontaneous vaginal delivery (OR 0.38, p < 0.0001). NFC was negatively associated
      (OR 0.10, p < 0.001) and trait anxiety was positively associated with intrapartum
      asphyxia (p < 0.05, rho = 0.582). In summary, physician cognitive processes and
      affect have a significant impact on patient outcomes, particularly in situations
      where there is a higher level of clinical unpredictability.

PMID- 19763857
TI  - Efficiency in chemistry: from hydrogen autotransfer to multicomponent catalysis.
AB  - A hydrogen autotransfer reaction has been applied to the alpha-alkylation of
      ketones, with primary alcohols as the electrophilic component, either under
      homogeneous (using a Ru complex as catalyst) or under heterogeneous (using Ni
      nanoparticles) conditions. This process is both very efficient (concerning atom
      economy) and ecologically friendly (water as the only by-product generated). On
      the other hand, three multicomponent reactions, namely, the Strecker reaction
      (without any catalyst), the aza-Sakurai process (catalyzed by ferrite), and the
      addition of in situ generated Zn enolates to chiral sulfinylimines (catalyzed by
      Cu), have proven to be very efficient in the generation of a diversity of
      polyfunctionalized molecules.

PMID- 19763858
TI  - One-pot synthesis of functionalized 4-oxo-2-thioxo-1,3-thiazinanes from primary
      amines, CS(2), and itaconic anhydride.
AB  - An efficient synthesis of 2-(3-alkyl-4-oxo-2- thioxo-1,3-thiazinan-5-yl)acetic
      acids is described via a three-component reaction between primary amines, CS(2),
      and itaconic anhydride.

PMID- 19763859
TI  - A synthesis of phosphorylated dioxohexahydropyrimidines from N,N'-dimethylurea,
      activated acetylenes, and trialkyl phosphites.
AB  - An efficient synthesis of alkyl 5-(dialkoxy- phosphoryl)-1,3-dimethyl-2, 6-dioxo
      hexahydropyrimidine-4-carboxylates is described. This involves the reaction of
      N,N'-dimethylurea and dialkyl acetylendicarboxylates in the presence of trialkyl
      phosphites. Under similar conditions, triphenyl phosphite led to alkyl 5
      (diphenoxyphosphoryl)-1,3-dimethyl-2,6-dioxo-hexahydro-4-pyrimidinecarboxylates.

PMID- 19763860
TI  - Multicomponent reactions of dimethyl methoxymalonate and dialkyl
      acetylenedicarboxylate in the presence of N-nucleophiles: one-pot synthesis of 2H
      pyridinyl-2-butenedioates in water.
AB  - An efficient synthesis of 2H-pyridinyl-2-butenedioate derivatives via reaction of
      dimethyl methoxymalonate and dialkyl acetylenedicarboxylate in the presence of N
      nucleophiles in water as a solvent is described.

PMID- 19763861
TI  - A simple and rapid protocol for the synthesis of phenacyl derivatives using
      macroporous polymer-supported reagents.
AB  - This article describes the use of Amberlite IRA-910 with different counter ions
      as excellent polymer-supported reagents in nucleophilic substitution reactions.
      The versatility of this protocol allowed the synthesis of a diversified library
      of phenacyl derivatives with high yields. The polymeric reagents can be reloaded
      several times with no loss of their efficiency.

PMID- 19763862
TI  - Induction of chromatin condensation by nuclear expression of a novel arginine
      rich cationic protein genetically engineered from the enhanced green fluorescent
      protein.
AB  - In the interphase nuclei of cultured cells, chromatin is compacted and organized
      in higher-order structures through the condensation and decondensation processes.
      Chromosomes in the interphase nucleus are known to occupy distinct territories.
      The chromosome territory-interchromatin compartment model premises that the
      interchromatin compartment is separated from compact higher-order chromatin
      domains and expands in between these chromatin-organized territories. Chromatin
      in cultured cells is compacted under some conditions, such as the stress of heat
      shock and high osmolarity, and Src-mediated nuclear tyrosine phosphorylation. We
      report here that a novel arginine-rich cationic protein is generated by
      frameshift mutation of enhanced green fluorescent protein (EGFP). The arginine
      rich cationic protein is highly hydrophilic and contains potential arginine-based
      nuclear localization signals. Expression of the arginine-rich cationic protein
      shows its predominant localization to the nucleus and induces striking chromatin
      condensation in the interphase, which might be involved in interchromatin spacing
      or euchromatinization. Thus, the arginine-rich cationic protein as a new tool
      would be useful for dissecting chromatin architecture dynamics.

PMID- 19763863
TI  - Administration of Bacillus coagulans in calves: recovery from faecal samples and
      evaluation of functional aspects of spores.
AB  - An investigation was carried out into the recovery from calf faeces of Bacillus
      coagulans spores added to the feed as probiotic. For this purpose, Bacillus
      coagulans spores (9 log10 CFU g-1) were given daily to 10 calves during the whole
      farming periods; another 10 calves acted as controls. Throughout the trial the
      faecal spore counts were significantly (P < 0.01) higher in the treated group
      than in the controls (averaging 2.1 x 105 vs 3.7 x 104 CFU g-1). Bacterial cells
      were recovered from faecal samples and ribotyping matched the strain isolated
      from faecal sample to the clone administered to the animals. In addition, the
      recovered cells were found to maintain their functionality aspects of acid
      production, survival in artificial gastric juice and in the presence of bile, and
      attachment to human intestinal epithelial cells. The results further elucidate
      the fate of spore formers administered to calves, and this will help in the
      development of new species-specific nutritional strategies.

PMID- 19763864
TI  - Identification of a hybridization window that facilitates sizeable reductions of
      pollen-mediated gene flow in spring wheat.
AB  - Transgenic wheat (Triticum aestivum L.) with improved agronomic traits is
      currently being field-tested. Gene flow in space is well-documented, but
      isolation in time has not received comparable attention. Here, we report the
      results of a field experiment that investigated reductions in intraspecific gene
      flow associated with temporal isolation of flowering between T. aestivum
      conspecifics. Pollen-mediated gene flow (PMGF) between an imazamox-resistant (IR)
      volunteer wheat population and a non-IR spring wheat crop was assessed over a
      range of volunteer emergence timings and plant population densities that
      collectively promoted flowering asynchrony. Natural hybridization events between
      the two populations were detected by phenotypically scoring plants in F(1)
      populations followed by verification with Mendelian segregation ratios in the
      F(1:2) lines. Based on the examination of >545,000 seedlings, we identified a
      hybridization window in spring wheat approximately 125 growing degree-days (GDD)
      in length. We found a sizeable reduction (two- to four-fold) in gene flow
      frequencies when flowering occurred outside of this window. The hybridization
      window identified in this research also will serve to temporally isolate
      neighboring wheat crops. However, strict control of volunteer populations or
      spatial isolation of neighbouring crops emerging within a 125 GDD hybridization
      window will be necessary to maintain low frequencies of PMGF in spring wheat
      fields. The model developed herein also is likely to be applicable to other wind
      pollinated species.

PMID- 19763865
TI  - A microbiological and serological study of leptospirosis among pigs in the
      Morogoro municipality, Tanzania.
AB  - Serological and microbiological studies on leptospirosis in pigs from Morogoro
      municipality, Tanzania were carried out between October 2007 and May 2008. Serum
      samples (n = 385) from apparently healthy pigs were tested by microscopic
      agglutination test for antibodies against live cultures of six known Leptospira
      interrogans serovars: Pomona, Icterohaemorrhagiae, Ballum, Tarassovi,
      Grippotyphosa and Hardjo. Significant positive titres were detected in 4.42%
      (17/385) of all the tested serum samples. Asceptically collected samples, urine
      (n = 236) and kidney tissues (n = 214), were cultured in enriched Fletcher's and
      Ellinghausen McCullough-Johnson and Harris media and assessed, at weekly
      intervals for 24 weeks, for growth by dark-field microscopy. Two leptospiral
      organisms were isolated from the urine samples. There was a statistical
      association between seroposivity and location that the subjects reside in (P <
      0.05), whereas it was not significantly associated with sex nor age (P > 0.05).
      The evidence of pig exposure to different serovars and the isolation of the
      leptospiral organisms confirm that the infection is present in pigs although with
      an overall low prevalence. Apart from its economic importance on to the pig
      industry, this disease is a potential zoonotic public health risk in Tanzania,
      especially because of the lack of studies on leptospirosis among persons who
      handle pigs and pork products.

PMID- 19763866
TI  - Porcine parvovirus- and porcine circovirus 2-associated reproductive failure and
      neonatal mortality in crossbred Indian pigs.
AB  - The objective of this study was to detect the presence of porcine parvovirus
      (PPV) and porcine circovirus 2 (PCV2) in a farm showing reproductive failure and
      increased mortality in neonatal piglets by histopathological examination,
      polymerase chain reaction, and demonstration of viral antigen and nucleic acid.
      Out of 594 piglets farrowed by 70 first-parity gilts, nine (1.51%) mummified
      fetuses, 13 (2.19%) stillborn, and 572 (96.3%) live-born piglets were recorded.
      The average litter size at birth was 8.48 piglets per litter. One hundred ninety
      four (33.91%) piglets died within 7 days of age. PPV was detected in five litters
      (7.14%) and two of them revealed coinfection with PCV2. The pathological lesions
      in the coinfected litters were more severe, indicating a synergistic action
      between the two viruses. Results of this study suggest for the first time
      occurrence of PPV and coinfection with PCV2 in crossbred Indian pigs affected
      with reproductive problem and neonatal mortality.

PMID- 19763867
TI  - Physiological change in camel milk composition (Camelus dromedarius) 2: physico
      chemical composition of colostrum.
AB  - Eleven samples of dromedary camel colostrum in Kazakhstan, which originated from
      one farm only, were collected to study the changes in the physico-chemical
      composition (total fat, total protein, iodine index, lactose, calcium,
      phosphorus, iron, vitamin C, urea, ammonia, density, Dornic acidity, pH, and
      skimmed dry matter) all along the first postpartum week. At that time, the fat
      matter decreased from 25.9% to 3.1% and protein from 17.2% to 4.2%, in contrast
      to vitamin C which increased. Minerals showed high variations with lower values
      the first day after parturition and variable changes up to the end of the week
      where the values were stabilized. The iron concentration decreased from the
      second day postpartum. No clear changes of the other parameters were observed,
      notably for the non-protein nitrogen (urea and ammonia).

PMID- 19763868
TI  - Direct and maternal (co)variance components, genetic parameters and annual trends
      for growth traits of Dorper sheep in semi-arid Kenya.
AB  - Genetic and phenotypic parameters were estimated for lamb growth traits for the
      Dorper sheep in semi-arid Kenya using an animal model. Data on lamb growth
      performance were extracted from available performance records at the Sheep and
      Goats Station in Naivasha, Kenya. Growth traits considered were body weights at
      birth (BW0, kg), at 1 month (BW1, kg), at 2 months (BW2, kg), at weaning (WW,
      kg), at 6 months (BW6, kg), at 9 months (BW9, kg) and at yearling (YW, kg),
      average daily gain from birth to 6 months (ADG(0-6), gm) and from 6 months to 1
      year (ADG(6-12), gm). Direct heritability estimates were, correspondingly, 0.18,
      0.36, 0.32, 0.28, 0.21, 0.14, 0.29, 0.12 and 0.30 for BW0, BW1, BW2, WW, BW6,
      BW9, YW, ADG(0-6) and ADG(6-12). The corresponding maternal genetic heritability
      estimates for body weights up to 9 months were 0.16, 0.10, 0.10, 0.19, 0.21 and
      0.18. Direct-maternal genetic correlations were negative and high ranging between
      -0.47 to -0.94. Negative genetic correlations were observed for ADG(0-6)-ADG(6
      12), BW2-ADG(6-12), WW-ADG(6-12) and BW6-ADG(6-12). Phenotypic correlations
      ranged from 0.15 to 0.96. Maternal effects are important in the growth
      performance of the Dorper sheep though a negative correlation exists between
      direct and maternal genetic effects. The current study has provided important
      information on the extent of additive genetic variation in the existing flocks
      that could now be used in determining the merit of breeding rams and ewes for
      sale to the commercial flocks. The estimates provided would form the basis of
      designing breeding schemes for the Dorper sheep in Kenya. Implications of the
      study to future Dorper sheep breeding programmes are also discussed.

PMID- 19763869
TI  - Pathotyping of a Newcastle disease virus isolated from peacock (Pavo cristatus).
AB  - This report describes Newcastle disease in peacock and the isolation and
      characterization of the virus. The virus had an intracerbral pathogenicity index
      of 1.71 and mean death time of 47 h. The isolate had multiple basic amino acids
      at the fusion protein cleavage site sequence ((110)GGRRQRRFIG(119)) with a
      phenylalanine at residue 117. Biological and molecular characterization revealed
      that the virus is velogenic. Phylogenetic analysis placed the isolate in genotype
      II.

PMID- 19763870
TI  - Effect of vitamin E and selenium supplementation on oxidative stress indices and
      cortisol level in blood in water buffaloes during pregnancy and early postpartum
      period.
AB  - Pregnancy is a physiology state accompanied by high energy and oxygen demand that
      may lead to increased level of oxidative stress and development of metabolic and
      reproductive disorders in pregnant water buffaloes. In the present study, the
      alterations in serum cortisol and erythrocyte lipid peroxides and superoxide
      dismutase activities were examined in 28 pregnant water buffaloes supplemented
      with antioxidant nutrients, Vitamin E and selenium. Another 14 buffaloes did not
      receive any treatment during pregnancy to serve as negative control. Results of
      the present study suggested that pregnancy is associated with oxidative stress
      and supplementation of vitamin E and selenium may be beneficial by alleviating
      oxidative stress in water buffaloes.

PMID- 19763872
TI  - Cryptococcus cerealis sp. nov. a psychrophilic yeast species isolated from
      fermented cereals.
AB  - Two yeast strains isolated in 2007 from fermented pig feed were studied,
      including the analysis of sequences of the D1/D2 and ITS-regions of the rDNA
      repeats, their morphology and nutritional physiology. Sequence comparison of the
      D1/D2 and ITS regions demonstrated that the strains do not belong to any known
      species. Therefore, a new species, Cryptococcus cerealis with the type strain CBS
      10505, is proposed. The species belongs to Filobasidiales (Agaricomycetes,
      Basidiomycota), and has Cryptococcus saitoi as the closest related species. The
      new species is psychrophilic, showing significant growth at 4 and 10 degrees C.

PMID- 19763871
TI  - Statins and vitamin D: a friendly association in pre-dialysis patients.
AB  - The increased mortality rate observed in patients with chronic kidney disease is
      related to the high prevalence of cardiovascular disease in this population.
      Recently, it has been shown that interventional therapy with statins and/or
      vitamin D could improve the outcomes of these patients. The aim of this study was
      to identify the risk factors for mortality in a group of patients with chronic
      kidney disease (stages 4 and 5--pre-dialysis) and verify whether vitamin D and
      statins could change the outcome. We included 95 patients (mean age--69.4) with
      stages 4 and 5 (pre-dialysis) of our "low-clearance" outpatient clinic, with an
      average eGFR of 16.9 ml/min and a mean follow-up of 24.1 months. Several
      biological, nutritional, laboratory and inflammatory parameters were analysed at
      baseline. Our population was divided into three groups: G-I, patients not
      medicated with either vitamin D or statins; G-II, patients medicated with either
      vitamin D or statins; and G-III, patients medicated with vitamin D and statins.
      We found (ANOVA) that the serum levels of pre-albumin (P = 0.018) and PTH (P =
      0.03) were lower in G-I. Concerning the inflammatory parameters, G-I showed
      higher levels of hsCRP (P = 0.014) and a trend to higher IL-6 levels (P = 0.077).
      We found the actuarial survival at 30 months (Kaplan-Meier), to be 56.4% in G-I,
      82.3% in G-II and 100% in G-III (log rank = 13.08 P = 0.0014). Using the Cox
      proportional hazards model, we found that the existence of coronary artery
      disease (P = 0.0001) and the absence of medication with vitamin D and/or statins
      (P = 0.005) independently influenced the mortality of our patients. In
      conclusion, we found, in our study, that patients under vitamin D and statins
      (with a synergistic effect) were less inflamed and showed a lower mortality rate.

PMID- 19763873
TI  - Phosphatidylglycerol depletion affects photosystem II activity in Synechococcus
      sp. PCC 7942 cells.
AB  - The role of phosphatidylglycerol (PG) in photosynthetic membranes of
      cyanobacteria was analyzed in a Synechococcus sp. PCC 7942 mutant produced by
      inactivating its cdsA gene presumably encoding cytidine 5'-diphosphate
      diacylglycerol synthase, a key enzyme in PG synthesis. In a medium supplemented
      with PG the Synechococcus sp. PCC 7942/DeltacdsA cells grew photoautotrophically.
      Depletion of PG in the medium resulted (a) in an arrest of cell growth and
      division, (b) in a suppression of O(2) evolving activity, and (c) in a
      modification of Chl fluorescence induction curves. Two-dimensional PAGE showed
      that in the absence of PG (a) the amount of the PSI monomers increased at the
      expense of the PSI trimers and (b) PSII dimers were decomposed into monomers.
      [(35)S]methionine labeling confirmed that PG depletion did not block the de novo
      synthesis of PSII proteins but slowed down the assembly of the newly synthesized
      D1 protein into PSII core complexes. Retailoring of PG was observed during PG
      depletion: the exogenously added artificial dioleoyl PG was transformed into
      photosynthetically more essential PG derivatives. Concomitantly with a decrease
      in PG content, SQDG content increased, but it could not restore photosynthetic
      activity.

PMID- 19763874
TI  - Protein dynamics investigated by neutron scattering.
AB  - This contribution describes incoherent quasielastic neutron scattering (QENS) as
      a suitable tool for investigations of protein dynamics with special emphasis on
      applications in photosynthesis research. QENS characterizes protein dynamics via
      the measurement of energy and momentum exchange between sample system and
      incident low-energy neutrons (1 meV<E<20 meV). This method is especially
      sensitive for picosecond motions of hydrogen atoms because it makes use of the
      exceptionally large incoherent neutron scattering cross section of protons and
      their almost homogeneous distribution in proteins. After a short introduction
      into the basic principles of neutron scattering, a more detailed description of
      QENS will be presented including a short overview on instrumentation and theory.
      Recent QENS results will be discussed for the antenna complex LHC II and PS II
      membrane fragments. It is shown that diffusive protein dynamics is indispensable
      for enabling Q(A)(-.) reoxidation by Q(B) at temperatures above 240 K, which
      explains the strong dependence of this electron transfer step on temperature and
      hydration level of the sample. Finally, a new laser-QENS pump-probe technique
      will be introduced which permits in situ monitoring of protein dynamics
      correlated with a change of the functional state of the sample, i.e. a direct
      observation of structure-dynamics-function relationships in real time.

PMID- 19763875
TI  - Fluorescence lifetime-resolved imaging.
AB  - This is a short account of fluorescence lifetime-resolved imaging, in order to
      acquaint readers who are not experts with the basic methods for measuring
      lifetime-resolved signals throughout an image. We present the early FLI
      (fluorescence lifetime imaging) history, review shortly the instrumentation and
      experimental design, discuss briefly the fundamentals of the measured
      fluorescence response, and introduce the basic measurement methodologies. We also
      emphasize the complex nature of the fluorescence response in FLI signals, and
      introduce certain analysis methods that are appropriate and informative for
      complex fluorescence decays. The advantages of model independent analyses are
      discussed and examples given.

PMID- 19763876
TI  - Assessment of obstruction length and optimal viewing angle from biplane X-ray
      angiograms.
AB  - Three-dimensional quantitative coronary angiography (3D QCA) has been encouraged
      by the increasing need to better assess vessel dimensions and geometry for
      interventional purposes. A novel 3D QCA system based on biplane X-ray angiograms
      is presented in this paper. By correcting for the isocenter offset and by
      improving the epipolar constraint for corresponding two angiographic projections,
      accurate and robust reconstruction of the vessel centerline is achieved and the
      reproducibility of its applications, e.g., the assessments of obstruction length
      and optimal viewing angle, is guaranteed. The accuracy and variability in
      assessing the obstruction length and optimal bifurcation viewing angle were
      investigated by using phantom experiments. The segment length assessed by 3D QCA
      correlated well with the true wire segment length (r (2) = 0.999) and the
      accuracy and precision were 0.04 +/- 0.25 mm (P < 0.01). 3D QCA slightly
      underestimated the rotation angle (difference: -1.5 degrees +/- 3.6 degrees , P <
      0.01), while no significant difference was observed for the angulation angle
      (difference: -0.2 degrees +/- 2.4 degrees , P = 0.54). In conclusion, the new 3D
      QCA approach allows highly accurate and precise assessments of obstruction length
      and optimal viewing angle from X-ray angiography.

PMID- 19763877
TI  - HIV infection and abnormal regional ventricular function.
AB  - To examine the effect of HIV infection on regional left ventricular dysfunction
      in cardiovascularly asymptomatic individuals. Nineteen HIV-negative and 27 HIV
      positive cardiovascularly asymptomatic study participants in Baltimore, Maryland
      were selected and underwent tagged cardiac magnetic resonance imaging. Regional
      left ventricular myocardial mid-wall peak systolic circumferential strain (Ecc)
      and early diastolic strain rate (SRE) of the left ventricle were assessed with
      the use of the harmonic phase analysis. The average Ecc and SRE measurements were
      compared between HIV-negative and HIV-positive individuals. Compared with the HIV
      negatives, the HIV-positives had lower average Ecc and SRE measurements in 90% of
      the 16 standard left ventricular segments. Of the 14 segments with decreased Ecc
      strain, 3 were statistically significant and of 14 with decreased strain rate
      (SRE), 6 were statistically significant. HIV infection may be associated with
      subclinical regional left ventricular systolic and diastolic dysfunction in
      individuals free of overt cardiovascular disease.

PMID- 19763878
TI  - Involvement of Ca(2+) channel signalling in sclerotial formation of Polyporus
      umbellatus.
AB  - Growth and morphogenesis transformation in Polyporus umbellatus were examined in
      the presence of various pharmacological compounds, to investigate signal
      transduction pathways that influence the development of sclerotia. Both the
      calcium channel blocker nifedipine and the calcium ionophor A23187 reduced
      sclerotial production in P. umbellatus; four classes of Ca(2+) signal agent
      including calcium chelators, calcium channel blockers, calcium ionophors and
      calmodulin inhibitors-were further studied. Among them, EGTA and BAPTA, as
      calcium chelators, exhibited a complete inhibitory effect on sclerotial
      formation, among the levels tested. Calcium channel blockers and calcium
      ionophors at the concentrations used in this study could not eliminate sclerotia
      formation completely, but did greatly reduce sclerotial production.
      Notoginsenoside in dosages >250 microg/ml produced a significant negative effect
      on mycelial growth, and it prevented sclerotial formation entirely at a dosage of
      500 microg/ml; no other drug influenced vegetative growth at all. The calcium
      ionophor A23187 did not decrease sclerotial mean weight at low doses (20 nM); at
      higher doses (200 nM), however, sclerotial development was significantly reduced,
      albeit not completely halted. The CaM inhibitors (W-7 and chlorpromazine) could
      each completely stop sclerotial formation. Using Fluo-3/AM as the indicator of
      cytosolic free calcium, the Ca(2+) content in the cytoplasm was found to have
      decreased significantly when hyphae were treated with different drugs, and there
      was no active Ca(2+) signal in the sclerotial mycelium. In general, the results
      suggest that Ca(2+) signal transduction may play an important role in sclerotial
      formation in P. umbellatus.

PMID- 19763879
TI  - Isolation, nucleotide identification and tissue expression of three novel ovine
      genes-SLC25A4, SLC25A5 and SLC25A6.
AB  - The complete coding sequences of three of sheep genes SLC25A4, SLC25A5 and
      SLC25A6 were firstly amplified using the reverse transcriptase polymerase chain
      reaction (RT-PCR) according to the conserved sequence information of the cattle
      or other mammals and known highly homologous sheep ESTs. Sheep SLC25A4, SLC25A5
      and SLC25A6 genes encode three corresponding proteins of 298 amino acids which
      contain the identically conserved putative mitochondrial carrier protein domain.
      Sheep SLC25A4 protein has high homology with the SLC25A4 proteins of six species
      cattle (99%), human (95%), rat (95%), mouse (94%), dog (94%) and chicken (89%).
      Sheep SLC25A5 protein has high identity with the SLC25A5 proteins of five species
      cattle (100%), dog (99%), mouse (98%), rat (98%) and human (98%). Sheep SLC25A6
      protein also has high homology with the SLC25A6 proteins of four species-cattle
      (99%), human (97%), pig (97%) and chicken (93%). The phylogenetic tree analysis
      demonstrated that sheep SLC25A4, SLC25A5 and SLC25A6 proteins share a common
      ancestor. Moreover, SLC25A4, SLC25A5 and SLC25A6 proteins present stronger
      interaction each other. The tissue expression analysis indicated that sheep
      SLC25A4, SLC25A5 and SLC25A6 genes were expressed in a range of tissues including
      leg muscle, kidney, skin, longissimus dorsi muscle, spleen, heart and liver. Our
      experiment is the first to provide the primary foundation for further insight
      into these three sheep genes.

PMID- 19763880
TI  - DNA methyltransferase expression differs with proliferation in childhood acute
      lymphoblastic leukemia.

PMID- 19763881
TI  - Molecular cloning and characterization of phospholipase D from Jatropha curcas.
AB  - Phospholipase D (PLD, EC 3.1.4.4) is a key enzyme involved in phospholipid
      catabolism, initiating a lipolytic cascade in membrane deterioration during
      senescence and stress, which was cloned from Jatropha curcas L., an important
      plant species as its seed is the raw material for biodiesels. The cDNA was 2,886
      bp in length with a complete open reading frame of 2,427 bp which encoded a
      polypeptide of 808 amino acids including a putative signal peptide of 53 amino
      acid residues and a mature protein of 755 amino acids with a predicted molecular
      mass of 86 kD and a pI of 5.44, having two highly conserved HKD' motifs.
      Phylogenetic analysis indicated the J. curcas PLD alpha (JcPLDalpha) showed a
      high similarity to other PLD alpha from plants. Semi-quantitative RT-PCR analysis
      revealed that it was especially abundant in root, stem, leaf, endosperm and
      flower, weakly in seed. And the JcPLDalpha was increasedly expressed in leaf
      undergoing environmental stress such as salt (300 mM NaCl), drought (30% PEG),
      cold (4degreeC) and heat (50degreeC). The JcPLDalpha protein was successfully
      expressed in Escherichia coli and showed high enzymatic activities. Maximal
      activity was at pH 8 and 60degreeC.

PMID- 19763882
TI  - Problems faced with legislating for IVF technology in a Roman Catholic country.
AB  - Malta traditionally enjoys a Roman Catholic Society, with the official religion
      of the country being cited in the second article of the constitution. Recently
      the government proposed to legislate to regulate human reproductive technology,
      in particular In Vitro Fertilization, which has been practiced for over two
      decades without controlling legislation. A Parliamentary Committee for social
      affairs was set up to study the situation inviting most stakeholders. The
      arguments gravitated mostly on issues of the status of the embryo and the media
      played a considerable role. At the end of the discussion the Archbishop made a
      statement which pointed out that IVF involves destruction of embryos and the
      process stopped. This article examines what caused the deterioration of the
      process and points favourably towards a way forward within the context of a
      Catholic Country.

PMID- 19763883
TI  - Contamination of tissue allografts from a deceased donor through haematic
      dissemination: a case study.
AB  - Infection is one of the most dangerous complications that can be seen when
      implanting bone or tendon allografts from a deceased donor. The most common germs
      isolated are found among the cutaneous florae, but sometimes they may be present
      in the bloodstream as a result of severe injuries suffered before the time of the
      decease. We present a case of contamination of allografts in a musculoskeletal
      tissue donor deceased after an accident, whose allografts were contaminated by
      gastrointestinal microorganisms, probably disseminated through the donor's blood.

PMID- 19763884
TI  - A PALB2 germline mutation associated with hereditary breast cancer in Italy.
AB  - Recently, it has been demonstrated that monoallelic PALB2 mutations predispose to
      familial breast cancer. We investigated the contribution of PALB2 mutations in a
      set of 132 Italian BRCA1/BRCA2-negative breast cancer families; one truncating
      PALB2 mutation, c.2257C>T, resulting in p.Arg753X, was identified in a woman and
      her daughter, with breast cancer diagnosed at 60 and 31 years old, respectively.
      This study supports the recent observation that PALB2 mutation are present,
      although infrequently, in familial BRCA1/BRCA2-negative breast cancer cases;
      moreover, it sustains latest evidences that some PALB2 mutations are associated
      with a substantially increased risk of breast cancer.

PMID- 19763885
TI  - Recommendations to improve identification of hereditary and familial colorectal
      cancer in Europe.
AB  - Familial colorectal cancer (CRC) accounts for 10-15% of all CRCs. In about 5% of
      all cases, CRC is associated with a highly penetrant dominant inherited syndrome.
      The most common inherited form of non-polyposis CRC is the Lynch syndrome which
      is responsible for about 2-4% of all cases. Surveillance of individuals at high
      risk for CRC prevents the development of advanced CRC. About 1 million
      individuals in Western Europe are at risk for Lynch syndrome. We performed a
      survey to evaluate the strategies currently used to identify individuals at high
      risk for CRC in 14 Western European countries. Questionnaires were distributed
      amongst members of a European collaborative group of experts that aims to improve
      the prognosis of families with hereditary CRC. The survey showed that in all
      countries obtaining a family history followed by referral to clinical genetics
      centres of suspected cases was the main strategy to identify familial and
      hereditary CRC. In five out of seven countries with a (regional or national) CRC
      population screening program, attention was paid in the program to the detection
      of familial CRC. In only one country were special campaigns organized to increase
      the awareness of familial CRC among the general population. In almost all
      countries, the family history is assessed when a patient visits a general
      practitioner or hospital. However, the quality of family history taking was felt
      to be rather poor. Microsatellite instability testing (MSI) or
      immunohistochemical analysis (IHC) of CRC are usually recommended as tools to
      select high-risk patients for genetic testing and are performed in most countries
      in patients suspected of Lynch syndrome. In one country, IHC was recommended in
      all new cases of CRC. In most countries there are no specific programs on cancer
      genetics in the teaching curriculum for medical doctors. In conclusion, the
      outcome of this survey and the discussions within an European expert group may be
      used to improve the strategies to identify individuals at high risk of CRC. More
      attention should be given to increasing the awareness of the general population
      of hereditary CRC. Immunohistochemical analysis or MSI-analysis of all CRCs may
      be an effective tool for identifying all Lynch syndrome families. The cost
      effectiveness of this approach should be further evaluated. All countries with a
      CRC population screening program should obtain a full family history as part of
      patient assessment.

PMID- 19763886
TI  - (1)H, (13)C and (15)N assignments of a camelid nanobody directed against human
      alpha-synuclein.
AB  - Nanobodies are single chain antibodies that are uniquely produced in Camelidae,
      e.g. camels and llamas. They have the desirable features of small sizes (Mw < 14
      kDa) and high affinities against antigens (Kd approximately nM), making them
      ideal as structural probes for biomedically relevant motifs both in vitro and in
      vivo. We have previously shown that nanobody binding to amyloidogenic human
      lysozyme variants can effectively inhibit their aggregation, the process that is
      at the origin of systemic amyloid disease. Here we report the NMR assignments of
      a new nanobody, termed NbSyn2, which recognises the C-terminus of the
      intrinsically disordered protein, human alpha-synuclein (aS), whose aberrant self
      association is implicated in Parkinson's disease.

PMID- 19763887
TI  - Receptor-targeted anticancer therapy.

PMID- 19763888
TI  - PDEF and PDEF-induced proteins as candidate tumor antigens for T cell and
      antibody-mediated immunotherapy of breast cancer.
AB  - Novel breast tumor antigens are needed to develop T cell and antibody-based
      vaccine immunotherapy approach against breast cancer. To this purpose, we have
      previously shown that PDEF is frequently over expressed in human breast tumors
      and exhibits highly restricted expression in normal human tissues that is
      primarily limited to normal prostate. Moreover, PDEF expression correlates with
      poor overall survival for breast cancer patients. Additionally, Pse (prostate
      specific Ets, mouse homologue of PDEF) is immunogenic in female mice and PDEF
      sequence contains HLA-A2 binding potentially immunogenic peptides. Together,
      these observations support PDEF as a novel candidate breast tumor antigen.
      Further, we have identified certain PDEF-induced proteins including CEACAM6, B7
      H4, and S100A7 as additional candidate breast tumor antigens.

PMID- 19763889
TI  - Regulatory T cells and immune tolerance to tumors.
AB  - Immune cells infiltrate tumors and make up a significant component of the
      multicellular cancer micro-environment, yet the immune system often fails to
      prevent tumor formation and progression. One explanation for this paradox is the
      presence of tolerance-promoting regulatory T cells (Tregs) that counteract
      antitumor immune cells. Tregs were known to be essential for maintaining self
      tolerance. Recently, Tregs have been found to promote tolerance to tumors in
      mouse models. Moreover, Treg infiltration in human tumors and malignant ascites
      is associated with worse clinical outcomes for various types of cancers. As many
      reviews have discussed the development and function of Tregs, this review focuses
      on the cellular and molecular mechanisms by which Tregs influence antitumor
      immune responses, and also discusses how these mechanisms might be exploited to
      develop innovative immune-based approaches that can improve cancer therapy.

PMID- 19763890
TI  - Strategies to enhance rituximab anti-tumor activity in the treatment of CD20
      positive B-cell neoplasms.
AB  - Rituximab is a chimeric monoclonal anti-CD20 antibody and was the first
      monoclonal antibody (mAb) therapy approved by FDA (Food and Drug Administration)
      for the treatment of B-cell lymphoma. It has revolutionized the treatment of
      patients with CD20-positive non-Hodgkin's lymphoma and CLL. Rituximab is
      currently being used in virtually all patients with B-cell lymphomas either alone
      or in combination with chemotherapy. Despite its excellent safety and efficacy
      profile, only a small portion of B-cell lymphoma patients treated with rituximab
      as a single agent have sustained complete remissions. Combining rituximab with
      standard chemotherapy regimens is associated with higher response rates, and
      improved survival in a subset of patients. Unfortunately, a significant
      percentage of patients who initially respond to rituximab eventually relapse, and
      there are patients that demonstrate intrinsic resistance to initial therapy. In
      the last decade, ongoing scientific research has led to a better understanding of
      rituximab-associated cytotoxic mechanisms against lymphoma target cells.
      Scientific efforts are increasingly being focused in developing new strategies to
      improve mAb activity. Various strategies include the following: combining
      rituximab with different biologic agents (e.g. cytokines, immunomodulatory
      drugs); developing novel antibody constructs (including bi-specific antibodies);
      and/or inhibiting signaling pathways associated with lymphomagenesis and immuno
      chemotherapy resistance. In this review article, we will provide an overview of
      various rituximab-associated cytotoxic mechanisms and novel strategies to improve
      mAb activity against B-cell lymphoma.

PMID- 19763891
TI  - Cancer vaccine with mimotopes of tumor-associated carbohydrate antigens.
AB  - The GD2 ganglioside, displayed by five carbohydrate Neu5Acalpha2-8Neu5Acalpha2
      3(GalNAcbeta1-4)Galbeta1-4Glcbeta residues attached to a ceramide chain that
      anchors the ganglioside in the cell membrane, is expressed on neuroectodermally
      derived tumors. GD2 has been used as a target for passive and active
      immunotherapy in patients with malignant melanoma and neuroblastoma. We have
      generated 47-LDA mimotope of GD2 by screening a phage display peptide library
      with anti-GD2 mAb 14G2a and reported that vaccination with the 47-LDA mimotope
      elicited GD2 cross-reactive IgG antibody responses as well as MHC class I
      restricted CD8(+) T cells to syngeneic neuroblastoma tumor cells. The cytotoxic
      activity of the vaccine-induced CTLs was independent of GD2 expression,
      suggesting recognition of a novel tumor-associated antigen cross-reacting with 47
      LDA. Immunoblotting studies using 14G2a mAb demonstrated that this antibody cross
      reacts with a 105 kDa glycoprotein expressed by GD2(+) and GD2(-) neuroblastoma
      and melanoma cells. Functional studies of tumor cells grown in three-dimensional
      (3D) collagen cultures with 14G2a mAb showed decreases in matrix
      metalloproteinase-2 activation, a process regulated by 105 kDa activated
      leukocyte cell adhesion molecules (ALCAM/CD166). The CD166 glycoprotein was shown
      to be recognized by 14G2a antibody, and inhibition of CD166 expression by RNA
      interference ablated the cell sensitivity to lysis by 47-LDA-induced CD8(+) T
      cells in vitro and in vivo. These results suggest that the vaccine-induced CTLs
      recognize a 47-LDA cross-reactive epitope expressed by CD166 and reveal a novel
      mechanism of induction of potent tumor-specific cellular responses by mimotopes
      of tumor-associated carbohydrate antigens.

PMID- 19763892
TI  - Enhancement of anti-tumor immunity by photodynamic therapy.
AB  - Photodynamic therapy (PDT) is an FDA-approved modality that rapidly eliminates
      local tumors, resulting in cure of early disease and palliation of advanced
      disease. PDT was originally considered to be a local treatment; however, both pre
      clinical and clinical studies have shown that local PDT treatment of tumors can
      enhance systemic anti-tumor immunity. The current state of investigations into
      the ability of PDT to enhance anti-tumor immunity, the mechanisms behind this
      enhancement and the future of PDT as an immunotherapy are addressed in this
      review.

PMID- 19763893
TI  - Review: Is lung inflammation associated with microbes and microbial toxins in
      cigarette tobacco smoke?
AB  - Chronic inflammation that has been observed for malignant and non-neoplastic lung
      diseases of smokers has been attributed to the numerous and diverse particulate
      ('tar')-phase and gas-phase chemicals in mainstream smoke, most of which arise
      from the burning of tobacco. The primary cell-mediator of lung inflammation is
      the macrophage. Most probably, inflammation is promoted also from some of the
      more than 50 other cell types of the lung. Cured tobacco in diverse types of
      cigarettes is known to harbor a plethora of bacteria (Gram-positive and Gram
      negative), fungi (mold, yeast), spores, and is rich in endotoxin
      (lipopolysaccharide). Reviewed herein are recent observations of the authors'
      team and other investigators that support the hypothesis that lung inflammation
      of long-term smokers may be attributed in part to tobacco-associated bacterial
      and fungal components that have been identified in tobacco and tobacco smoke.

PMID- 19763894
TI  - Non-canonical Wnt signaling pathways in hematopoiesis.
AB  - Hematopoietic stem cells (HSCs) are a rare population of cells that are
      responsible for life-long generation of blood cells of all lineages. In order to
      maintain their numbers, HSCs must establish a balance between the opposing cell
      fates of self-renewal and initiation of hematopoietic differentiation. Multiple
      signaling pathways have been implicated in the regulation of HSC cell fate. One
      such set of pathways are those activated by the Wnt family of ligands. The
      function of the canonical Wnt signaling pathway, which utilizes beta-catenin to
      regulate gene expression, has been extensively studied in hematopoiesis. However,
      there is a growing body of evidence that the other Wnt signaling pathways, termed
      non-canonical, also play an important role. In this review, we will discuss the
      regulation of hematopoiesis by the Wnt signaling pathways, focusing on the
      potential functions of non-canonical Wnt signaling pathways.

PMID- 19763895
TI  - Evaluation of oxalate decarboxylase and oxalate oxidase for industrial
      applications.
AB  - Increased recirculation of process water has given rise to problems with
      formation of calcium oxalate incrusts (scaling) in the pulp and paper industry
      and in forest biorefineries. The potential in using oxalate decarboxylase from
      Aspergillus niger for oxalic acid removal in industrial bleaching plant filtrates
      containing oxalic acid was examined and compared with barley oxalate oxidase. Ten
      different filtrates from chemical pulping were selected for the evaluation.
      Oxalate decarboxylase degraded oxalic acid faster than oxalate oxidase in eight
      of the filtrates, while oxalate oxidase performed better in one filtrate. One of
      the filtrates inhibited both enzymes. The potential inhibitory effect of selected
      compounds on the enzymatic activity was tested. Oxalate decarboxylase was more
      sensitive than oxalate oxidase to hydrogen peroxide. Oxalate decarboxylase was
      not as sensitive to chlorate and chlorite as oxalate oxidase. Up to 4 mM chlorate
      ions, the highest concentration tested, had no inhibitory effect on oxalate
      decarboxylase. Analysis of the filtrates suggests that high concentrations of
      chlorate present in some of the filtrates were responsible for the higher
      sensitivity of oxalate oxidase in these filtrates. Oxalate decarboxylase was thus
      a better choice than oxalate oxidase for treatment of filtrates from chlorine
      dioxide bleaching.

PMID- 19763896
TI  - Response surface optimization of medium components for naringinase production
      from Staphylococcus xylosus MAK2.
AB  - Response surface methodology was used to optimize the fermentation medium for
      enhancing naringinase production by Staphylococcus xylosus. The first step of
      this process involved the individual adjustment and optimization of various
      medium components at shake flask level. Sources of carbon (sucrose) and nitrogen
      (sodium nitrate), as well as an inducer (naringin) and pH levels were all found
      to be the important factors significantly affecting naringinase production. In
      the second step, a 22 full factorial central composite design was applied to
      determine the optimal levels of each of the significant variables. A second-order
      polynomial was derived by multiple regression analysis on the experimental data.
      Using this methodology, the optimum values for the critical components were
      obtained as follows: sucrose, 10.0%; sodium nitrate, 10.0%; pH 5.6; biomass
      concentration, 1.58%; and naringin, 0.50% (w/v), respectively. Under optimal
      conditions, the experimental naringinase production was 8.45 U/mL. The
      determination coefficients (R(2)) were 0.9908 and 0.9950 for naringinase activity
      and biomass production, respectively, indicating an adequate degree of
      reliability in the model.

PMID- 19763897
TI  - Ca2+ concentrations are key determinants of ischemia-reperfusion-induced
      apoptosis: significance for the molecular mechanism of Bcl-2 action.
AB  - The mechanism of action of the anti-apoptotic oncogene Bcl-2 and Ca2+ regulation
      in ischemia-reperfusion injury is still obscure. In this present study, we
      investigated mitochondrial Ca2+ overloads and mechanism of action of Bcl-2.
      Eighteen Wistar rats were divided into sham-operated control group (I) (n = 6),
      ischemia and reperfusion group (II) (n = 6), and amlodipine-treated group (1 mg
      kg(-1) body weight/daily by oral route for 7 days before inducing ischemia
      reperfusion maneuver) (III) (n = 6). Rats were subjected to 1 h of hepatic
      ischemia followed by 3-h reperfusion. Mitochondrial Ca2+ content was determined
      and damage was confirmed by transmission electron microscopy. Decrease of
      mitochondrial Ca2+ level is related to reduction of apoptosis and cellular
      changes, viz. increased Bcl-2 expression followed by reduction in secondary
      endoplasmic reticulum, whereas ischemia/reperfusion group shows overloading Ca2+
      ions and decrease in Bcl-2 expression as compared to sham-operated rats. Thus,
      Bcl-2-dependent reduction of Ca2+ is an important component of the anti-apoptotic
      program in ischemia-reperfusion injury.

PMID- 19763898
TI  - Kinetic evaluation of aminoethylisothiourea on mushroom tyrosinase activity.
AB  - This study demonstrates that aminoethylisothiourea (AET), a potent inhibitor of
      inducible nitric oxide synthase, is an irreversible competitive inhibitor of
      mushroom tyrosinase by chelation to the active site of tyrosinase when L-3,4
      dihydroxyphenylalanine was assayed spectrophotometrically. The spectrophotometric
      recordings of the inhibition of tyrosinase by AET were characterized by the
      presence of a lag period prior to the attainment of an inhibited steady-state
      rate. The lag period corresponded to the time in which AET was reacting with the
      enzymatically generated o-quinone. Increasing AET concentrations provoked longer
      lag periods as well as a concomitant decrease in the tyrosinase activity. Both
      lag period and steady-state rate were dependent on AET, substrate, and tyrosinase
      concentrations. The inhibition of diphenolase activity of tyrosinase by AET
      showed positive kinetic cooperativity which arose from the protection of both
      substrate and o-quinone against inhibition by AET. The UV-visible spectrum of a
      mixture of tyrosinase and AET exhibited a characteristic shoulder peak ascribed
      to the chelation of AET to the active site of tyrosinase. Moreover, the presence
      of copper ions only partially prevented but not reverted mushroom tyrosinase
      inhibition when CuSO(4) was added to the assay medium on tyrosinase activity.

PMID- 19763899
TI  - Thermodynamic feasibility of enzymatic reduction of carbon dioxide to methanol.
AB  - Production of valuable chemicals from CO(2) is highly desired for the purpose of
      controlling CO(2) emission. Toward that, enzymatic reduction of CO(2) for the
      production of methanol appeared to be especially promising. That has been
      achieved by reversing the biological metabolic reaction pathways. However,
      hitherto, there has been little discussion on the thermodynamic feasibility of
      reversing such biological pathways. The reported yields of methanol have been
      generally very low under regular reaction conditions preferred by naturally
      evolved enzymes. The current work examines the sequential enzymatic conversion of
      CO(2) into methanol from a thermodynamic point of view with a focus on factors
      that control the reaction equilibrium. Our analysis showed that the enzymatic
      conversion of carbon dioxide is highly sensitive to the pH value of the reaction
      solution and, by conducting the reactions at low pHs (such as pH 6 or 5) and
      ionic strength, it is possible to shift the biological methanol metabolic
      reaction equilibrium constants significantly (by a factor of several orders of
      magnitude) to favor the synthesis of methanol.

PMID- 19763900
TI  - New potential biocatalysts by laccase immobilization in PVA Cryogel type carrier.
AB  - Laccases are enzymes belonging to the Oxidoreductases class. These enzymes may be
      good biocatalysts for different processes, at laboratory and industrial levels. A
      successful use at industrial scale demands a higher stability of the enzyme. As
      an easy way to obtain longer life biocatalysts, the immobilization process is
      recommended. Thus, the paper presents different ways of obtaining new
      biocatalysts by a laccase covalent immobilization on a macroporous carrier based
      on poly(vinyl alcohol) cryogel. Different procedures of covalent immobilization
      are described, the newly obtained biocatalysts being characterized. According to
      the experimental data, the stability of the immobilized enzyme increased and the
      pH profile changed, compared with those of the free enzyme.

PMID- 19763901
TI  - Gene cloning, expression, and characterization of recombinant aerolysin from
      Aeromonas hydrophila.
AB  - Aerolysin is a significant virulent toxin protein secreted by Aeromonas
      hydrophila; it produces deep wound infections and hemorrhagic septicemia. The
      complete aerolysin gene (1,482 bp) was amplified from A. hydrophila. Furthermore,
      it was cloned and expressed into Escherichia coli BL21(DE3) codon plus RP cells
      using 0.5 mM IPTG for induction. The protein size was 54 kDa as estimated by SDS
      PAGE, and it was purified by Ni-NTA affinity chromatography. Anti-His antibodies
      were used to characterize the expressed aerolysin by Western blotting and showed
      hemolytic activity with fish red blood cells. Aerolysin may be used as
      immunoassays for earlier control of A. hydrophila and is also compatible for
      vaccination.

PMID- 19763902
TI  - alpha-Amylase: an ideal representative of thermostable enzymes.
AB  - The conditions prevailing in the industrial applications in which enzymes are
      used are rather extreme, especially with respect to temperature and pH.
      Therefore, there is a continuing demand to improve the stability of enzymes and
      to meet the requirements set by specific applications. In this respect,
      thermostable enzymes have been proposed to be industrially relevant. In this
      review, alpha-amylase, a well-established representative of thermostable enzymes,
      providing an attractive model for the investigation of the structural basis of
      thermostability of proteins, has been discussed.

PMID- 19763903
TI  - Antiarrhythmic effects of some antioxidant vitamins in rats injected with
      epinephrine.
AB  - Since excessive amounts of catecholamines are known to produce arrhythmias and
      increase the plasma level of aminochrome, an oxidation product of catecholamines,
      we tested the hypothesis that antioxidants may reduce the formation of
      aminochrome and prevent the catecholamine-induced arrhythmias. For this purpose,
      Sprague-Dawley rats were pretreated orally, with vitamin A or vitamin C for 21
      days, and their effects on ventricular arrhythmias induced by a bolus dose or
      cumulative doses of intravenous epinephrine were examined. Electrocardiogram
      recording of these animals revealed that pretreatment with either of these
      vitamins increased the time of onset and decreased the duration of the
      epinephrine-induced ventricular arrhythmias. Ventricular fibrillations due to
      high doses of epinephrine were also prevented by the antioxidant pretreatment.
      Although pretreatment with either vitamin A or vitamin C did not affect the basal
      malondialdehyde level in control animals, the increase in malondialdehyde level
      caused by epinephrine administration was significantly reduced by these agents.
      The elevated level of plasma aminochrome due to epinephrine was also decreased by
      vitamins A and C treatments. The results indicate that antioxidant may prevent
      catecholamine-induced arrhythmias by reducing the formation of aminochrome and
      thus may provide a new strategy for the management of stress-related heart
      disease.

PMID- 19763904
TI  - Intraductal pancreatic neuroendocrine tumor.
AB  - Intraductal lesions of the pancreas are usually due to intraductal papillary
      mucinous neoplasms and the less common intraductal tubular adenoma. Cases of
      acinar cell carcinoma within intraductal location have also been encountered
      recently. Pancreatic neuroendocrine tumors are rarely encountered within the main
      pancreatic duct. A 74-year-old male presented with non-specific abdominal
      symptoms and was found to have an obstructive lesion in the main pancreatic duct
      with associated chronic pancreatitis. A distal pancreatectomy was performed which
      revealed a solid and cystic tumor measuring 6 x 3 x 2 cm situated wholly within
      the main pancreatic duct. It formed an obstructing intraluminal polypoid lesion
      that resulted in surrounding chronic pancreatitis. Microscopic evaluation of the
      mass showed it to be a well-differentiated pancreatic neuroendocrine tumor with
      entrapped, non-malignant tubules. Intraductal pancreatic neuroendocrine tumors
      may occur in two settings. Firstly, and more commonly, there is a parenchymal
      based tumor that then encroaches on and pushes into the main pancreatic duct. The
      less common scenario is of a primary intraductal location without a pancreatic
      parenchymal lesion. While an intraductal location of a pancreatic neuroendocrine
      tumor is rare, it should be borne in mind when confronted by an intraductal
      lesion in the pancreas.

PMID- 19763905
TI  - The therapeutic potential of microRNAs in nervous system damage, degeneration,
      and repair.
AB  - MicroRNAS (miRNAs) have been suggested to play important roles in the central
      nervous system during development as well as disease. miRNAs appear to be
      dysregulated in a number of neurodegenerative diseases, developmental disorders,
      and as a result of stroke. Each miRNA has the ability to regulate hundreds of
      messenger RNA transcripts, both by causing degradation of the mRNA and by
      inhibition of protein translation. Recent findings suggest that it may eventually
      be possible to treat some neurological disorders by restoring or inhibiting
      miRNAs altered by disease pathology. Both viral delivery and administration of
      modified oligonucleotides mimicking or inhibiting specific miRNAs have been
      effective in model systems. Artificial miRNAs have also been generated for the
      repression of specific transcripts. Alteration of miRNA expression by disease and
      insult also holds the potential for improved diagnostic tools. Finally, miRNAs
      have been shown to control cellular proliferation and specification, suggesting
      that manipulation of miRNAs in cultured cells could result in more convenient
      generation of pure cell populations for transplantation.

PMID- 19763906
TI  - The role of the complement system and the activation fragment C5a in the central
      nervous system.
AB  - The complement system is a pivotal component of the innate immune system which
      protects the host from infection and injury. Complement proteins can be induced
      in all cell types within the central nervous system (CNS), where the pathway
      seems to play similar roles in host defense. Complement activation produces the
      C5 cleavage fragment C5a, a potent inflammatory mediator, which recruits and
      activates immune cells. The primary cellular receptor for C5a, the C5a receptor
      (CD88), has been reported to be on all CNS cells, including neurons and glia,
      suggesting a functional role for C5a in the CNS. A second receptor for C5a, the
      C5a-like receptor 2 (C5L2), is also expressed on these cells; however, little is
      currently known about its potential role in the CNS. The potent immune and
      inflammatory actions of complement activation are necessary for host defense.
      However, if over-activated, or left unchecked it promotes tissue injury and
      contributes to brain disease pathology. Thus, complement activation, and
      subsequent C5a generation, is thought to play a significant role in the
      progression of CNS disease. Paradoxically, complement may also exert a
      neuroprotective role in these diseases by aiding in the elimination of aggregated
      and toxic proteins and debris which are a principal hallmark of many of these
      diseases. This review will discuss the expression and known roles for complement
      in the CNS, with a particular focus on the pro-inflammatory end-product, C5a. The
      possible overarching role for C5a in diseases of the CNS is reviewed, and the
      therapeutic potential of blocking C5a/CD88 interaction is evaluated.

PMID- 19763907
TI  - Central nervous system regeneration inhibitors and their intracellular
      substrates.
AB  - Injury to the central nervous system (CNS) initiates a cascade of responses that
      is inhibitory to the regeneration of neurons and full recovery. At the site of
      injury, glial cells conspire with an inhibitory biochemical milieu to construct
      both physical and chemical barriers that prevent the outgrowth of axons to or
      beyond the lesion site. These inhibitors include factors derived from myelin,
      repulsive guidance cues, and chondroitin sulfate proteoglycans. Each bind
      receptors on the axon surface to initiating intracellular signaling cascades that
      ultimately result in cytoskeletal reorganization and growth cone collapse. Here,
      we present an overview of the molecules, receptors, and signaling pathways that
      inhibit CNS regeneration, with a particular focus on the intracellular signaling
      machinery that may function as convergent targets for multiple inhibitory
      ligands.

PMID- 19763908
TI  - Identification of the trans-activation domain and the nuclear location signals of
      human zinc finger protein HZF1 (ZNF16).
AB  - We previously characterized a C2H2-type zinc finger protein HZF1 (ZNF16) and
      demonstrated its important role in erythroid and megakaryocytic differentiation.
      This protein was located in nucleus. In this study, we first approved that HZF1
      solely could activate lacZ reporter gene in yeast host Y190. This self-activation
      phenomenon together with structure and distribution of HZF1 suggested it as a
      potential transcription factor. By the auto-activation experiments and the
      luciferase reporter system and deletion mutation analysis, we further located the
      trans-activation domain at amino acid residences 49-197 within the non-zinc
      finger region of HZF1. An acidic residue-rich subregion (amino acids 49-105) was
      important for the trans-activation effect, but it could not function
      independently. By deletion mutation analysis, we also identified three nuclear
      location signals, which were located in the regions of amino acids 255-280, 328
      360, and 460-490, respectively, and all of them within the zinc finger region.

PMID- 19763912
TI  - A critical role of surgery in the treatment for paraneoplastic pemphigus caused
      by localized Castleman's disease.
AB  - Paraneoplastic pemphigus (PNP) is an autoimmune mucocutaneous disease associated
      with lymphoproliferative tumors, and sometimes with a very rare tumor,
      Castleman's disease (CD). PNP can present as a variety of dermatological
      diseases, and so far, only limited studies of PNP caused by CD have been
      reported, resulting in its higher possibility of misdiagnosis. Because of the
      variability of clinical presentation of PNP caused by CD, selection of the
      appropriate therapeutic approach remains unclear. To investigate the efficacy of
      surgery to patients with PNP caused by localized CD, the clinical, laboratory and
      pathological data of 5 patients with PNP caused by localized CD, 3 females and 2
      males, aged 34 years (ranging from 29 to 42), with the tumor size from 6 x 4 x 4
      cm(3) to 8 x 8 x 7 cm(3), located in the mediastinum (n = 3) and retroperitoneum
      (n = 2), were compared before and after surgery. All patients underwent surgery,
      and the diagnosis was confirmed by pathological examination. Surgery
      significantly improved mucosal lesions, cured skin lesions and decreased serum
      pemphigus autoantibody 6 months after surgery. Most patients were followed up for
      6-48 months, and they all had no clinical or radiological recurrence and remain
      disease free. Therefore, surgery is an effective approach to cure patients with
      PNP caused by localized CD.

PMID- 19763913
TI  - Anti-p53 antibodies in serum: relationship to tumor biology and prognosis of
      breast cancer patients.
AB  - The aim of this study was to analyze the concentration of anti-p53 antibodies in
      the serum of breast cancer patients and to correlate these results with various
      clinical, pathological and biochemical parameters. We also wanted to assess the
      prognostic significance of these antibodies in our patients. Sera from 61
      patients with breast cancer and 20 individuals without malignancies were analyzed
      using enzyme-linked immunoadsorbent assay. High levels of anti-p53 antibodies
      were detected in twenty-one (35%) breast cancer patients and one control (5%).
      The difference was statistically significant. We observed an inverse relationship
      between the anti-p53 antibodies and the age of the patients. We found significant
      association of anti-p53 antibodies with tumor size, histological grade of the
      tumors and the number of axillary lymph nodes involved. The levels of anti-p53
      antibodies were higher in patients with negative estrogen and progesterone
      receptors in comparison with patients with positive steroid receptors, but the
      difference was not statistically significant. No relation was observed between
      anti-p53 antibodies neither with the Cathepsin D levels in the cytosol nor with
      the HER-2/neu extracellular domain in the serum. Patients with primary tumors and
      higher levels of anti-p53 antibodies had shorter 5-year survival than patients
      with lower levels of anti-p53 antibodies. Our results support the role of anti
      p53 antibodies as a biomarker of less favorable phenotype as well as a prognostic
      factor for patients with breast cancer.

PMID- 19763914
TI  - p120ctn isoform 1 expression significantly correlates with abnormal expression of
      E-cadherin and poor survival of lung cancer patients.
AB  - Different p120ctn isoforms exert different, even opposing, effects on tumor cell
      growth depending on the level of E-cadherin expression, but the impact on
      clinicopathological parameters of lung cancer patients is not clear. Herein, we
      investigate the correlation between pan-p120ctn, p120ctn isoform 1, and E
      cadherin expression and clinicopathological parameters, especially prognosis, of
      lung cancer patients. Immunohistochemistry on 20 specimens of normal bronchial
      epthelium revealed that, p120ctn isoform 1 was not expressed at the membrane;
      only weak cytoplasmic expression was seen. In contrast, both pan-p120ctn and E
      cadherin were expressed clearly on the cell membrane or in the cytoplasmic peri
      membrane region. However, in squamous cell lung cancer or lung adenocarcinomas,
      p120ctn isoform 1 over-expressed in the cytoplasm accompany with the abnormal pan
      p120ctn and E-cadherin cytoplasm expression. p120ctn isoform 1 over-expression
      correlated positively with lymph node metastasis, poor differentiation,
      histological type, and high TNM stage. Cytoplasmic p120ctn isoform 1 expression
      in metastatic nodules was always higher than in the primary tumor. While the mean
      survival times of patients with normal p120 ctn isoform 1 or pan-p120ctn
      expression differed significantly, the mean survival times of patients with
      abnormal expression were similar. Lymph node metastasis, TNM stage, abnormal pan
      p120ctn expression, and p120ctn isoform 1 over-expression were all independent
      factors affecting the prognosis of lung cancer patients. Over-expression of
      p120ctn isoform 1 positively correlated with poor prognosis of lung cancer
      patients, and therefore may be a useful marker of lung cancer patient survival.

PMID- 19763915
TI  - Prognostic significance of tissue factor pathway inhibitor-2 in pancreatic
      carcinoma and its effect on tumor invasion and metastasis.
AB  - Tissue factor pathway inhibitor-2 (TFPI-2) is a matrix-associated kunitz-type
      serine proteinase inhibitor that plays an important role in plasmin and trypsin
      mediated activation of zymogen matrix metalloproteinases involved in tumor
      angiogenesis, invasion and metastasis. Earlier studies have shown that the
      production of TFPI-2 is downregulated during the progression of various tumors.
      To detect whether TFPI-2 can be expressed in human pancreatic carcinoma samples,
      to evaluate its prognostic significance on pancreatic carcinoma and to
      investigate its effect on tumor invasion and metastasis, we collected 9 normal
      pancreatic tissue samples and 41 pancreatic carcinoma samples and stably
      transfected the human pancreatic carcinoma cell line Panc-1 with a vector capable
      of expressing TFPI-2 gene. RT-PCR and Western blot analysis revealed that the
      expression of TFPI-2 in pancreatic carcinoma samples was markedly lower than that
      in normal pancreas samples, and there was no TFPI-2 expression in Panc-1 cell.
      Its expression was related with biological characters of pancreatic carcinoma.
      The results of Boyden chamber assay and orthotopic pancreatic carcinoma model
      showed that TFPI-2 could inhibit invasion and metastasis ability of pancreatic
      carcinoma in vitro and in vivo. Kaplan-Meier survival curve and Cox proportional
      hazards model assay identified TFPI-2 as an independent prognostic factor for
      pancreatic carcinoma. Our data suggest that TFPI-2 plays a significant role in
      the invasion and metastasis of pancreatic carcinoma cell in vitro and in vivo and
      is determined to be an important prognostic factor for pancreatic carcinoma
      patients.

PMID- 19763916
TI  - Evaluation of PTEN and Mcl-1 expressions in NSCLC expressing wild-type or mutated
      EGFR.
AB  - Signaling pathways activated by epidermal growth factor receptors (EGFRs) are
      important in lung carcinogenesis. New treatment strategies with EGFR-targeting
      drugs provided improvements in management of lung cancer. However, molecular
      mechanisms underlying resistance to these drugs need to be evaluated. Surgically
      resected samples were obtained from 50 patients with non-small-cell-lung cancer.
      PTEN, Mcl-1 and EGFR protein expression levels were evaluated by Western-blot.
      Direct sequencing was performed to investigate EGFR tyrosine kinase domain
      mutations. We detected c.2235-2249 (pGlu746-Ala750del) mutation in exon 19 in two
      patients with adenocarcinoma histology. Elevated expression levels of both Mcl-1
      isoforms (Mcl-1S and Mcl-1XL) and EGFR proteins were found in 15 (30%) and 23
      (46%) of the cases, respectively. Reduced PTEN protein expression levels were
      observed in 17 (34%) of the cases. PTEN expression level was reduced in 26% of
      cases that showed increased EGFR expression. Also, increased expression of Mcl-1
      protein was observed in 26% of cases with EGFR overexpression. One of the cases
      harboring pGlu746-Ala750del mutation had increased levels of Mcl-1 and decreased
      PTEN expression levels. Our results indicate that, in addition to lack of PTEN
      expression, elevated levels of the Mcl-1 protein might be one of the important
      intrinsic mechanisms protecting non-small-cell-lung cancer cells from apoptosis
      induced by several compounds. Therefore, EGFR mutations in conjunction with
      evaluation of Mcl-1 and PTEN expression levels in large cohorts might provide
      important clues for improvements of new treatment strategies in non-small-cell
      lung cancer management.

PMID- 19763918
TI  - Postmenopausal bleeding as first sign of an acute myelogenous leukaemia: A case
      report and review of the literature.
AB  - Postmenopausal bleeding (PMB) can have various causes and malignancy must always
      be excluded. Extramedullary manifestations of a haematological disease in the
      female genital tract are rare. We present the case of a woman with PMB as the
      first sign of an acute myelogenous leukaemia (AML). An 81-year-old patient
      presented with PMB. Manual and colposcopic examination raised suspicion of a
      cervical carcinoma, but histopathology and cervical Pap smear altered the
      diagnosis to granulocytic sarcoma (GS), an extramedullary manifestation of AML.
      The patient had a normal blood count 2 weeks prior to the examination, but at the
      time of presentation her leukocytes had risen to 116000/microl. The patient died
      3 days later due to a pulmonary embolism, most probably as a result of
      leukostasis. In this case, GS of the cervix was the first sign of the AML with
      simultaneous appearance of leukocytosis and peripheral blasts. PMB was the reason
      for presentation. GS of the female genital tract is very rare and diagnosis is
      challenging, especially on the basis of the Pap smear. Abnormal inflammatory
      cells must be a warning sign and an indication for further examinations. GS as
      the presenting sign of AML has a poor prognosis with only 6% of patients
      surviving for more than 2 years.

PMID- 19763917
TI  - Arsenic trioxide induces apoptosis in NB-4, an acute promyelocytic leukemia cell
      line, through up-regulation of p73 via suppression of nuclear factor kappa B
      mediated inhibition of p73 transcription and prevention of NF-kappaB-mediated
      induction of XIAP, cIAP2, BCL-XL and survivin.
AB  - The purpose of the present study is to evaluate the effects of arsenic trioxide
      (ATO) on human acute promyelocytic leukemia NB-4 cells. Microculture tetrazolium
      test, bromodeoxyuridine (BrdU) cell proliferation assay, caspase 3 activity
      assay, cell-based nuclear factor kappa B (NF-kappaB) phosphorylation measurement
      by ELISA and real-time RT-PCR were employed to appraise the effects of ATO on
      metabolic activity, DNA synthesis, induction of programmed cell death and NF
      kappaB activation. The suppressive effects of ATO on metabolic potential, cell
      proliferation and NF-kappaB activation were associated with induction of
      apoptosis in NB-4 cells. In addition, an expressive enhancement in mRNA levels of
      p73, cyclin-dependent kinase inhibitor 1A (p21), tumor protein 53-induced nuclear
      protein 1 (TP53INP1), WNK lysine deficient protein kinase 2 (WNK2) and lipocalin
      2 coupled with a significant reduction in transcriptional levels of NF-kappaB
      inhibitor beta (IKK2), Nemo, BCL2-like 1 (BCL-X(L)), inhibitor of apoptosis
      protein 1 (cIAP2), X-linked inhibitor of apoptosis protein (XIAP), survivin, Bcl
      2, TIP60, ataxia telangiectasia (ATM), SHP-2 and sirtuin (SIRT1) were observed.
      Altogether, these issues show for the first time that ATO treatment could trammel
      cell growth and proliferation as well as induces apoptosis in NB-4 cells through
      induction of transcriptional levels of p73, TP53INP1, WNK2, lipocalin 2 as well
      as suppression of NF-kappaB-mediated induction of BCL-X(L), cIAP2, XIAP and
      survivin. Furthermore, the inductionary effects of ATO on transcriptional
      stimulation of p73 might be through cramping the NF-kappaB module (through
      suppression of p65 phosphorylation as well as transcriptional hindering of IKK2,
      ATM and Nemo) along with diminishing the mRNA expression of TIP60, SHP-2 and
      SIRT1.

PMID- 19763919
TI  - Modes of defining atherosclerosis in mouse models: relative merits and evolving
      standards.
AB  - Mouse models have become the most common model for defining mechanisms of
      atherosclerotic disease. Many genetic manipulations have enabled the development
      of atherosclerosis in mice due to either endogenous or diet-induced
      hypercholesterolemia. This availability of lesion-susceptible mice has
      facilitated many studies using pharmacological and genetic approaches.
      Unfortunately, this expansive literature on mouse atherosclerosis has generated
      many contradictions on the role of specific pathways. A contributor to these
      inconsistencies may be the multiple modes in which atherosclerosis is evaluated.
      Also, for each specific technique, there are no consistent standards applied to
      the measurements. This chapter will discuss the imaging, biochemical, and
      compositional modes of evaluating atherosclerosis with suggestions for standard
      execution of these techniques.

PMID- 19763920
TI  - Evaluating micro- and macro-vascular disease, the end stage of atherosclerosis,
      in rat models.
AB  - Development of effective treatment or, more critically, preventative measures
      against atherosclerosis and cardiovascular disease will require animal models
      that mimic the disease processes seen in humans and permit identification of the
      genetic and physiological factors. The Rat is normally resistant to
      cardiovascular disease, but a number of genetic mutations make affected strains
      of rats highly susceptible to atherosclerosis and micro- and macro-vascular
      disease that is highly analogous to human disease. These models of obesity
      develop the metabolic syndrome and type 2 diabetes, hyperinsulinemia,
      hyperlipidemia, vascular and myocardial dysfunction, and end-stage lesions in the
      heart and kidney. The models offer the prospect of both genetic and molecular
      biology studies that are linked directly to spontaneous cardiovascular disease
      and exploration of putative preventative or treatment approaches, including
      pharmaceutical agents. Use of small animal models of cardiovascular disease is
      dependent on appropriate experimental design and techniques that take account of
      the complex nature of the disease processes. Detailed experimental procedures for
      the use of rat models, including handling and treatment of animals, choice of
      experimental variables and endpoints, assay methods, and histological and
      electron microscopy techniques are covered in this chapter.

PMID- 19763921
TI  - Non-invasive blood pressure measurement in mice.
AB  - Hypertension is a leading cause of heart attack, stroke, and kidney failure and
      represents a serious medical issue worldwide. The genetic basis of hypertension
      is well-established, but few causal genes have been identified thus far. Non
      invasive blood pressure measurements are a critical component of high-throughput
      genetic studies to identify genes controlling blood pressure. Whereas this
      technique is fairly routine for blood pressure measurements in rats, non-invasive
      blood pressure measurement in mice has proven to be more challenging. This
      chapter describes an experimental protocol measuring blood pressure in mice using
      a CODA non-invasive blood pressure monitoring system. This method enables
      accurate blood pressure phenotyping in mice for linkage or mutagenesis studies,
      as well as for other experiments requiring high-throughput blood pressure
      measurement.

PMID- 19763922
TI  - Direct blood pressure monitoring in laboratory rodents via implantable radio
      telemetry.
AB  - The ability to monitor and record precise blood pressure fluctuations in research
      animals is vital to research for human hypertension. Direct measurement of blood
      pressure via implantable radio telemetry devices is the preferred method for
      automatic collection of chronic, continuous blood pressure data. Two surgical
      techniques are described for instrumenting the two most commonly used laboratory
      rodent species with radiotelemetry devices. The basic rat procedure involves
      advancing a blood pressure catheter into the abdominal aorta and placing a radio
      transmitting device in the peritoneal cavity. The mouse technique involves
      advancing a thin, flexible catheter from the left carotid artery into the aortic
      arch and placing the telemetry device under the skin along the animal's flank.
      Both procedures yield a chronically instrumented model to provide accurate blood
      pressure data from an unrestrained animal in its home cage.

PMID- 19763923
TI  - Measuring kidney function in conscious mice.
AB  - Mice lacking or over-expressing a gene of experimental interest have become
      important tools to understand the regulation of kidney function and water and
      electrolyte homeostasis. The use of mice in physiological studies is becoming
      more widespread, but there are still a number of technical limitations that
      preclude the full utilization of mouse models in renal research. The present
      chapter focuses upon a set of methods developed in our laboratory to quantify
      renal function in conscious mice. These measurements are based upon surgical
      instrumentation of mice with chronic indwelling arterial and venous catheters.
      This preparation permits direct measurement of arterial blood pressure, direct
      sampling of arterial and/or venous blood, intravenous or intra-arterial infusion
      of substances, and quantification of daily sodium balance. The advantage of these
      techniques is that all of these procedures can be performed in conscious mice
      freely moving in their home cages. As such, this in vivo preparation provides an
      assessment of physiological function in mice in their native state.

PMID- 19763924
TI  - Ischemic stroke in mice and rats.
AB  - Ischemic stroke occurs most often in the territory of the middle cerebral artery
      (MCA) in humans. Since its description in rats more than two decades ago, the
      minimally invasive intraluminal suture occlusion of MCA is an increasingly used
      model of stroke in both rats and mice due to its ease of inducing ischemia and
      achieving reperfusion under well-controlled conditions. This method can be used
      under the guidance of laser-Doppler flowmetry to ascertain the magnitude of
      occlusion or reperfusion and to decrease the rate of subarachnoid hemorrhage.
      Ninety minutes of transient ischemia in the territory of MCA results in
      substantial and reproducible ischemic lesions in both the striatum and the
      cortex, with characteristics of lesion core and penumbra. Thus, this model is
      applicable to neuroprotective drug studies, including ischemic brain lesion
      evaluation (either in vivo with magnetic resonance imaging or post-mortem with
      brain tissue staining) and neurological status (motor deficits simply assessed by
      a six-point neurological score scale) as outcome parameters.

PMID- 19763925
TI  - Mouse surgical models in cardiovascular research.
AB  - Mouse models that mimic human diseases are important tools for investigating
      underlying mechanisms in many disease states. Although the demand for these
      models is high, there are few schools or courses available for surgeons to obtain
      the necessary skills. Researchers are usually exposed to brief descriptions of
      the procedures in scientific journals, which they then attempt to reproduce by
      trial and error. This often leads to a number of mistakes and unnecessary loss of
      animals. This chapter provides comprehensive details of three major surgical
      procedures currently employed in cardiovascular research: aortic constriction (of
      both ascending and transverse portions), pulmonary artery banding, and myocardial
      infarction (including ischemia-reperfusion). It guides the reader through the
      entire procedure, from the preparation of the animal for surgery until its full
      recovery, and includes a list of all necessary tools and devices. Due
      consideration has been given to the pitfalls and possible complications in the
      course of surgery. Adhering to our recommendations should improve reproducibility
      of the models and bring the number of the animal subjects to the minimum.

PMID- 19763926
TI  - Echocardiographic examination in rats and mice.
AB  - Rats and mice are the predominant experimental species in cardiovascular research
      due to the widespread availability of genetic and transgenic rodent models of
      heart disease. Phenotyping of these models requires reliable and reproducible
      methods to noninvasively and serially assess cardiovascular structure and
      function. However, the small size of rodents has presented a challenge. Many of
      these challenges have been overcome in recent years due to significant
      technological advances in echocardiographic capabilities. For example, improved
      spatial resolution and increased frame rates have allowed more precise and
      accurate quantification of diminutive structures, myocardial function, and blood
      flow in mice. Consequently, transthoracic echocardiography (TTE) has emerged as a
      popular and powerful tool for cardiac phenotypic characterization in rodents.
      This chapter will focus on the use of TTE in rodents for evaluating (1) left
      ventricular (LV) chamber dimensions and wall thickness, (2) LV mass, (3) global
      LV systolic and diastolic function, (4) regional LV systolic function by newly
      developed tissue Doppler imaging (TDI), and (5) hemodynamic parameters.
      Reliability of these measurements depends on various factors such as the skill
      and experience of the sonographer and the image analyzer, the type, depth, and
      duration of anesthesia, and animal characteristics. These topics will also be
      discussed.

PMID- 19763927
TI  - QTL mapping in intercross and backcross populations.
AB  - In the past two decades, various statistical approaches have been developed to
      identify quantitative trait locus with experimental organisms. In this chapter,
      we introduce several commonly used QTL mapping methods for intercross and
      backcross populations. Important issues related to QTL mapping, such as threshold
      and confidence interval calculations are also discussed. We list and describe
      five public domain QTL software packages commonly used by biologists.

PMID- 19763928
TI  - Quantitative trait locus analysis using J/qtl.
AB  - Quantitative trait locus (QTL) analysis is a statistical method to link
      phenotypes with regions of the genome that affect the phenotypes in a mapping
      population. R/qtl is a powerful statistical program commonly used for analyzing
      rodent QTL crosses, but R/qtl is a command line program that can be difficult for
      novice users to run. J/qtl was developed as an R/qtl graphical user interface
      that enables even novice users to utilize R/qtl for QTL analyses. In this
      chapter, we describe the process for analyzing rodent cross data with J/qtl,
      including data formatting, data quality control, main scan QTL analysis, pair
      scan QTL analysis, and multiple regression modeling; this information should
      enable new users to identify QTL affecting phenotypes of interest within their
      rodent cross datasets.

PMID- 19763929
TI  - Computing genetic imprinting expressed by haplotypes.
AB  - Different expression of maternally and paternally inherited alleles at certain
      genes is called genetic imprinting. Despite its great importance in trait
      formation, development, and evolution, it remains unclear how genetic imprinting
      operates in a complex network of interactive genes located throughout the genome.
      Genetic mapping has proven to be a powerful tool that can estimate the
      distribution and effects of imprinted genes. While traditional mapping models
      attempt to detect imprinted quantitative trait loci based on a linkage map
      constructed from molecular markers, we have developed a statistical model for
      estimating the imprinting effects of haplotypes composed of multiple sequenced
      single-nucleotide polymorphisms. The new model provides a characterization of the
      difference in the effect of maternally and paternally derived haplotypes, which
      can be used as a tool for genetic association studies at the candidate gene or
      genome-wide level. The model was used to map imprinted haplotype effects on body
      mass index in a random sample from a natural human population, leading to the
      detection of significant imprinted effects at the haplotype level. The new model
      will be useful for characterizing the genetic architecture of complex
      quantitative traits at the nucleotide level.

PMID- 19763930
TI  - Haplotype association mapping in mice.
AB  - Haplotype Association Mapping (HAM) is a novel phenotype-driven approach to
      identify genetic loci and was originally developed for mice. This method, which
      is similar to Genome-Wide Association (GWA) studies in humans, looks for
      associations between the phenotype and the haplotypes of mouse inbred strains,
      treating inbred strains as individuals. Although this approach is still in
      development, we review the current literature, present the different methods and
      applications that are in use, and provide a glimpse of what is to come in the
      near future.

PMID- 19763931
TI  - Candidate gene association analysis.
AB  - Candidate gene association study is the most common method for associating human
      genetic variations with the phenotypes they produce, due to the relative
      simplicity of acquiring patient samples and genotype data. The study design
      begins with identifying appropriate DNA samples and an appropriate phenotype for
      analysis. The candidate genes and polymorphisms must then be chosen. After
      genotyping the candidate genes in the DNA samples, the results are checked to
      ensure appropriate quality and association analysis is performed. The raw results
      are interpreted and placed into context and follow-up analysis is carried out to
      validate and refine the findings. A wide range of software packages are available
      for both the association analysis and other steps in the study. This chapter
      describes the use of PLINK as the analysis tool in an example, as that suite has
      emerged as the most popular option for genetic association testing.

PMID- 19763932
TI  - Genome-wide association study in humans.
AB  - Genome-wide association studies have opened a new era in the study of the genetic
      basis of common, multifactorial diseases and traits. Before the introduction of
      this approach only a handful of common genetic variants showed consistent
      association for any phenotype. Using genome-wide association, scores of novel and
      unsuspected loci have been discovered and later replicated for many complex
      traits. The principle is to genotype a dense set of common genetic variants
      across the genomes of individuals with phenotypic differences and examine whether
      genotype is associated with phenotype. Because the last common human ancestor was
      relatively recent and recombination events are concentrated in focal hotspots,
      most common variation in the human genome can be surveyed using a few hundred
      thousand variants acting as proxies for ungenotyped variants. Here, we describe
      the different steps of genome-wide association studies and use a recent study as
      example.

PMID- 19763933
TI  - Bioinformatics analysis of microarray data.
AB  - Gene expression profiling provides unprecedented opportunities to study patterns
      of gene expression regulation, for example, in diseases or developmental
      processes. Bioinformatics analysis plays an important part of processing the
      information embedded in large-scale expression profiling studies and for laying
      the foundation for biological interpretation. Over the past years, numerous tools
      have emerged for microarray data analysis. One of the most popular platforms is
      Bioconductor, an open source and open development software project for the
      analysis and comprehension of genomic data, based on the R programming language.
      In this chapter, we use Bioconductor analysis packages on a heart development
      dataset to demonstrate the workflow of microarray data analysis from annotation,
      normalization, expression index calculation, and diagnostic plots to pathway
      analysis, leading to a meaningful visualization and interpretation of the data.

PMID- 19763934
TI  - eQTL analysis in mice and rats.
AB  - Since the introduction of genetical genomics in 2001, many studies have been
      published on various organisms, including mouse and rat. Genetical genomics makes
      use of the latest microarray profiling technologies and combines vast amounts of
      genotype and gene expression information, a strategy that has proven very
      successful in inbred line crosses. The data are analyzed using standard tools for
      linkage analysis to map the genetic determinants of gene expression variation.
      Typically, studies have singled out hundreds of genomic loci regulating the
      expression of nearby and distant genes (called local and distant expression
      quantitative trait loci, respectively; eQTLs). In this chapter, we provide a step
      by-step guide to performing genome-wide linkage analysis in an eQTL mapping
      experiment by using the R statistical software framework.

PMID- 19763935
TI  - eQTL analysis in humans.
AB  - Improving human health is a major aim of medical research, but it requires that
      variation between individuals be taken into account since each person carries a
      different combination of gene variants and is exposed to different environmental
      conditions, which can cause differences in susceptibility to diseases. With the
      advent of molecular markers in the 1980s, it became possible to genotype
      individuals (i.e., to detect the presence or absence of local DNA sequence
      variants at each of hundreds of genome positions). This DNA sequence variation
      could then be related to disease susceptibility by using pedigree data. Such
      linkage analyses proved to be difficult for more complex diseases. Recently, with
      the decreasing costs of genotyping, analyses of large natural populations of
      unrelated individuals became possible and resulted in the association of many
      genes (and genetic variants in these genes) with complex diseases. Unfortunately,
      for a considerable proportion of these genes and their proteins, it is not yet
      clear what their downstream effects are. Studying the expression of these genes
      and proteins can help to uncover the effects of these variants on the expression
      of these and other genes, proteins, metabolites, and phenotypes. In this chapter,
      we focus on the high-throughput and genome-wide measurement of gene expression in
      a natural population of unrelated humans, and on the subsequent association of
      variation in expression to "expression quantitative trait loci" (eQTLs) on DNA
      using oligonucleotide arrays with hundreds of thousands of single-nucleotide
      polymorphism (SNP) markers that capture most of the human genetic variation well.
      This strategy has been successfully applied to several diseases such as celiac
      disease (Hunt et al. 2008, Nat Genet 40, 395-402) and asthma (Moffatt et al.
      2007, Nature 448, 470-473): associated genetic variants have been identified that
      affect levels of gene expression in cis or in trans, providing insight into the
      biological pathways affected by these diseases.

PMID- 19763936
TI  - A systematic strategy for the discovery of candidate genes responsible for
      phenotypic variation.
AB  - It is increasingly common to combine genome-wide expression data with
      quantitative trait mapping data to aid in the search for sequence polymorphisms
      responsible for phenotypic variation. By joining these complex but different data
      types at the level of the biological pathway, we can take advantage of existing
      biological knowledge to systematically identify possible mechanisms of genotype
      phenotype interaction. With the development of web services and workflows, this
      process can be made rapid and systematic. Our methodology was applied to a use
      case of resistance to African trypanosomiasis in mice. Workflows developed in
      this investigation, including a guide to loading and executing them with example
      data, are available at http://www.myexperiment.org/users/43/workflows .

PMID- 19763937
TI  - Introduction: emerging themes in DNA topoisomerase research.
AB  - DNA topoisomerases are enzymes that alter the topology of DNA. They have
      important functions in DNA replication, transcription, Holliday junction
      dissolution, chromosome condensation, and sister chromatid separation.
      Deficiencies in these enzymes are associated with diseases that result from
      genome instability. The last 10-15 years has seen a great deal of exciting
      research in the field of topoisomerase. Here we discuss a selection of the new
      themes that have been recently introduced into the already large body of
      topoisomerase research.

PMID- 19763938
TI  - Analysis of DNA topoisomers, knots, and catenanes by agarose gel electrophoresis.
AB  - Agarose gel electrophoresis is by far the most widely used method for
      characterizing the topological state of DNA molecules. Although this technique
      has been used for more than 30 years, the physical mechanism underlying the
      resolution of topological states remains poorly understood. However,
      electrophoretic methods remain the most robust and precise techniques for
      determining the local unwinding of DNA induced by the binding of proteins and
      small-molecule ligands, analyzing conformational transitions in duplex DNA,
      measuring changes in helical repeat that accompany shifts in environmental
      conditions, and characterizing knotting and linking in duplex DNA.

PMID- 19763939
TI  - Two-dimensional agarose gel electrophoresis of DNA topoisomers.
AB  - The electrophoretic velocity of a duplex DNA ring is mainly determined by its
      overall shape. Consequently, DNA topoisomers of opposite supercoiling handedness
      can have identical gel velocity, and topoisomers highly supercoiled cannot be
      separated beyond some point. These problems are overcome by two-dimensional
      agarose gel electrophoresis, which involves two successive electrophoresis steps
      in one gel slab. The first and second electrophoresis steps are conducted in
      orthogonal directions with different concentrations of DNA intercalating agents.
      These compounds alter the overall shape of the DNA and, thereby, change the
      relative mobility of individual DNA topoisomers.

PMID- 19763940
TI  - Cleavage of plasmid DNA by eukaryotic topoisomerase II.
AB  - Topoisomerase II is an essential enzyme that is required for a number of critical
      nuclear processes. All of the catalytic functions of topoisomerase II require the
      enzyme to generate a transient double-stranded break in the backbone of the
      double helix. To maintain genomic integrity during the cleavage event,
      topoisomerase II forms covalent bonds between active site tyrosyl residues and
      the newly generated 5'-DNA termini. In addition to the critical cellular
      functions of the type II enzyme, several important anticancer drugs kill cells by
      increasing levels of covalent topoisomerase II-DNA cleavage complexes. Due to the
      physiological importance of topoisomerase II and its role in cancer chemotherapy,
      several methods have been developed to monitor the in vitro DNA cleavage activity
      of the type II enzyme. The plasmid-based system described in this chapter
      quantifies enzyme-mediated double-stranded DNA cleavage by monitoring the
      conversion of covalently closed supercoiled DNA to linear molecules. The assay is
      simple, straightforward, and does not require the use of radiolabeled substrates.

PMID- 19763941
TI  - Assays for the preferential binding of human topoisomerase I to supercoiled DNA.
AB  - To assay the preferential binding of eukaryotic type IB topoisomerases to
      supercoiled DNA, two methods are described that make use of a catalytically
      inactive mutant form of the enzyme. In the gel shift assay, the preference for
      binding to supercoiled plasmid DNA is detected in the presence of linear and
      nicked forms of the same DNA by a reduction in the mobility of the supercoiled
      plasmid during electrophoresis in agarose. The more quantitative filter binding
      assay compares the ability of nicked and supercoiled forms of the circular DNA to
      compete for the binding of a (3)H-labeled nicked DNA to the topoisomerase where
      the enzyme-DNA complexes are quantitated by the retention of the labeled DNA on a
      nitrocellulose membrane.

PMID- 19763942
TI  - Monitoring the topoisomerase II DNA gate conformational change with fluorescence
      resonance energy transfer.
AB  - Type II DNA topoisomerases are essential, ubiquitous enzymes responsible for
      performing vital functions in chromosome condensation and segregation and in
      regulating intracellular DNA supercoiling. Topoisomerase II (topo II) performs
      these DNA transactions by passing one segment of DNA through the other using a
      reversible, enzyme-bridged double-stranded DNA break. This cleavage/religation of
      the DNA backbone is coupled to the opening and closing of the DNA gate, a
      critical step for strand passage during the catalytic cycle. To monitor the
      opening and closing of the DNA gate, we designed an oligonucleotide substrate
      with a pair of fluorophores flanking the topoisomerase II cleavage site, such
      that the fluorophores undergo efficient fluorescence resonance energy transfer
      (FRET) in the intact DNA substrate, but the FRET efficiency decreases as topo II
      opens the DNA gate. Here we present a method for creating the DNA substrate and
      using it as a tool to monitor the conformational changes at the topo II DNA gate.
      We detail how to collect and process fluorescence spectra to determine the FRET
      efficiency of the DNA substrate.

PMID- 19763943
TI  - Single-molecule magnetic tweezers studies of type IB topoisomerases.
AB  - The past few years have seen the application of single-molecule force
      spectroscopy techniques to the study of topoisomerases. Magnetic tweezers are
      particularly suited to the study of topoisomerases due to their unique ability to
      exert precise and straightforward control of the supercoiled state of DNA. Here,
      we illustrate in a stepwise fashion how the dynamic properties of type IB
      topoisomerases can be monitored using this technique.

PMID- 19763944
TI  - Dissolution of double Holliday junctions by the concerted action of BLM and
      topoisomerase IIIalpha.
AB  - In eukaryotic cells, topoisomerase III forms an evolutionarily conserved complex
      with a RecQ family helicase and two OB-fold containing proteins, replication
      protein A (RPA) and RMI1. One role for this complex is to catalyze the completion
      of homologous recombination reactions in which the recombining DNA molecules are
      covalently interlinked by a double Holliday junction structure. This process,
      which requires the single-stranded DNA decatenation activity of topoisomerase
      III, is termed Holliday junction "dissolution" to distinguish it from Holliday
      junction "resolution" catalyzed by endonucleases (resolvases) that simply cleave
      the four-way junction. Holliday junction dissolution gives rise exclusively to
      non-cross-over recombinant products, which would have the effect of suppressing
      sister chromatid exchanges and loss of heterozygosity between homologous
      chromosomes. In this chapter, we provide a detailed experimental protocol for the
      preparation of an oligonucleotide-based, double Holliday junction substrate and
      for the biochemical analysis of dissolution in vitro.

PMID- 19763945
TI  - ChIP-on-chip analysis of DNA topoisomerases.
AB  - Here we describe an adapted ChIP-on-chip protocol for the analysis of DNA
      topoisomerase chromosomal binding in Saccharomyces cerevisiae cells. The ChIP-on
      chip technique is based on the immunoprecipitation of crosslinked chromatin
      (ChIP, chromatin immunoprecipitation), followed by DNA amplification and
      hybridization to high-density oligonucleotide arrays (Chip). Comparison of the
      signal intensities of immunoprecipitated and control fractions provides a
      measurement of the protein-DNA association along entire genomes. ChIP-on-chip
      analysis of DNA topoisomerase binding to chromosomal DNA opens a window to the
      understanding of the in vivo contribution of these enzymes to the different DNA
      transactions taking place concomitantly within the context of the highly
      organized eukaryotic genome. Chromosomal binding profiles obtained from
      synchronized cells allow scoring the temporal and spatial restriction of these
      enzymes at different cell cycle stages. By using this approach, novel aspects of
      DNA topoisomerase function in chromosome metabolism might be unmasked.

PMID- 19763946
TI  - Analyzing Top2 distribution on yeast chromosomes by chromatin
      immunoprecipitation.
AB  - In vertebrate cells, DNA topoisomerase II (Topo II), named Top2 in yeast,
      localizes along chromosome axes early in mitosis and concentrates within
      centromeric chromatin during metaphase. The factors controlling these changes in
      enzyme distribution are largely unknown. Insight into Topo II dynamics could
      potentially be derived through genetic approaches in yeast. In practice, however,
      the small size and limited compaction of yeast chromosomes has precluded a
      detailed analysis of Top2 localization along mitotic chromosomes. As an
      alternative approach, we describe a method for examining Top2 distribution using
      chromatin immunoprecipitation (ChIP). By adding a detergent solubilization step,
      this method allows efficient recovery of DNA sequences associated with Top2 in
      the insoluble chromosome scaffold fraction.

PMID- 19763947
TI  - Binding of DNA topoisomerases I and II to replication origins.
AB  - The interaction of DNA topology modifying enzymes with eukaryotic DNA replication
      origins can be detected with nucleotide precision exploiting the action of enzyme
      poisons specific for type I or type II DNA topoisomerases. Using the
      topoisomerase I poison camptothecin and the topoisomerase II poison VP16, the
      precise sites of interaction of these enzymes around the lamin B2 origin have
      been identified at different points in the cell cycle. The procedure can be
      applied to any origin for which the sequence has been identified within
      approximately 1 kb.

PMID- 19763948
TI  - Cytometric assessment of DNA damage induced by DNA topoisomerase inhibitors.
AB  - Exposure of cells to inhibitors of DNA topoisomerase I (topo I) or topoisomerase
      II (topo II) leads to DNA damage that often involves formation of DNA double
      strand breaks (DSBs). DNA damage, particularly induction of DSBs, manifests by
      phosphorylation of histone H2AX on Ser-139 which is mediated by one of the
      protein kinases of the phosphoinositide kinase family, namely ATM, ATR, and/or
      DNA-PK. The presence of Ser-139 phosphorylated H2AX (gammaH2AX) is thus a
      reporter of DNA damage. This protocol describes quantitative assessment of
      gammaH2AX detected immunocytochemically in individual cells combined with
      quantification of cellular DNA content by cytometry. The bivariate analysis of
      gammaH2AX expression versus DNA content allows one to correlate DNA damage with
      the cell cycle phase or DNA ploidy. The protocol can also be used to assess
      activation (Ser-1981 phosphorylation) of ATM; this event also revealing DNA
      damage induced by topo I or topo II inhibitors. Examples where DNA damage was
      induced by topotecan (topo I) and etoposide (topo II) inhibitors are provided.

PMID- 19763949
TI  - Analysis of the topoisomerase II-dependent decatenation G2 checkpoint and
      checkpoint kinases in human cells.
AB  - Inhibition of Topo II function using poisons and catalytic inhibitors triggers
      checkpoints that act to delay progression of G2 cells into mitosis. Topo II
      poisons induce Topo II-associated DNA double-strand breaks that activate ATM and
      the DNA damage G2 checkpoint. Topo II catalytic inhibitors do not induce DNA
      double-strand breaks but block decatenation of intertwined daughter chromatids.
      Complete decatenation before anaphase of mitosis is required for chromatid
      segregation. G2 cells appear to sense the degree of chromatid arm catenations and
      actively delay the onset of mitosis by sustaining the inhibition of mitosis
      promoting factor (MPF) and polo-like kinase 1 (Plk-1) kinase activities that
      normally propel G2 cells into mitosis. This chapter details the methods for assay
      of decatenation G2 checkpoint function and checkpoint kinase activities.

PMID- 19763950
TI  - Assaying topoisomerase II checkpoints in yeast.
AB  - Topoisomerase II activity is crucial to maintain genome stability through the
      removal of catenanes in the DNA formed during DNA replication and scaffolding the
      mitotic chromosome. Perturbed Topo II activity causes defects in chromosome
      segregation due to persistent catenations and aberrant DNA condensation during
      mitosis. Recently, novel top2 alleles in the yeast Saccharomyces cerevisiae
      revealed a checkpoint control that responds to perturbed Topo II activity.
      Described in this chapter are protocols for assaying the phenotypes seen in top2
      mutants on a cell biological basis in live cells: activation of the Topo II
      checkpoint using spindle morphology, chromosome condensation using fluorescently
      labeled chromosomal loci, and cell cycle progression by flow cytometry. Further
      characterization of this novel checkpoint is warranted so that we can further our
      understanding of the cell cycle, genomic stability, and the possibility of
      identifying novel drug targets.

PMID- 19763951
TI  - Cytological analysis of chromosome structural defects that result from
      topoisomerase II dysfunction.
AB  - For analyzing chromosome structural defects that result from topoisomerase II
      (topo II) dysfunction, we have adapted classical cell cycle experiments,
      classical cytological techniques, and the use of a potent topo II inhibitor (ICRF
      193). In this chapter, we describe in detail the protocols used and we discuss
      the rationale for our choice and for the adaptations applied. We clarify in which
      cell cycle stages each of the different chromosomal aberrations induced by
      inhibiting topo II take place: lack of chromosome segregation, undercondensation,
      lack of sister chromatid resolution, and lack of chromosome individualization. We
      also put these observations into the context of the two topo II-dependent cell
      cycle checkpoints.

PMID- 19763952
TI  - Top2 SUMO conjugation in yeast cell lysates.
AB  - DNA topoisomerase II (Topo II), named Top2 in budding and fission yeast, is a
      conserved target of the SUMO modification pathway, with SUMO-conjugated forms of
      Topo II accumulating specifically during mitosis in both yeast and vertebrate
      cells (Bachant et al., Mol Cell 9, 1169-82, 2002; Azuma et al., J Cell Biol 163,
      477-87, 2003; Dawlaty et al., Cell 133, 103-15, 2008). As with many SUMO
      substrates, the functional significance of this modification is still
      incompletely understood and, perhaps surprisingly, better characterized in
      vertebrates than yeasts. It seems likely, however, that continued analysis of
      yeast Top2 SUMO modification will reveal commonalities with vertebrate cells,
      leading to a deeper understanding of how sumoylation regulates Topo II function.
      Toward this end, we describe a protocol for analyzing yeast Top2 SUMO conjugates
      in vivo.

PMID- 19763953
TI  - Analysis of SUMOylation of topoisomerase IIalpha with Xenopus egg extracts.
AB  - Posttranslational protein modification by the Small Ubiquitin-like MOdifiers
      (SUMO) is involved in many cellular functions including organization of nuclear
      structures and chromatin, transcriptional regulation, and nucleo-cytoplasmic
      transport. Both genetic and biochemical studies indicate that the SUMO
      modification pathway plays an important role in proper cell cycle control,
      especially in the normal progression of mitosis. DNA topoisomerase II has been
      shown to be modified by SUMO in budding yeast as well as in vertebrates. We have
      shown by biochemical analysis using the Xenopus egg extract (XEE) cell-free assay
      system that DNA topoisomerase IIalpha (Topo IIalpha) is modified by SUMO-2/3 on
      mitotic chromosomes in the early stages of mitosis. Inhibition of mitotic
      SUMOylation in the XEE assay system causes aberrant sister chromatid separation
      in anaphase and alters Topo IIalpha association with chromosomes.

PMID- 19763954
TI  - The dynamics of DNA topoisomerase IIalpha in living cells.
AB  - Here, we describe methods to prepare a mammalian expression plasmid encoding EGFP
      fused to the amino-terminus of human DNA topoisomerase IIalpha (Topo IIalpha) for
      use in studying the dynamics of Topo IIalpha in living cells. In previous
      studies, this plasmid was transfected into LLC-Pk cells, a porcine epithelial
      cell line that remains relatively flat during mitosis. After selection for stable
      integration, cells were cloned by serial dilution in microwells and used to grow
      a stable cell line expressing EGFP-Topo IIalpha; this cell line was termed LPk
      GT2. Using photobleaching methods with conventional and patterned photobleaching,
      LPk-GT2 cells were used to demonstrate the rapid dynamics of Topo IIalpha
      exchange in both interphase nuclei and mitotic chromosomes. These rapid dynamics
      are dependent on enzyme activity since ICRF159, a catalytic inhibitor of Topo
      IIalpha, slows dynamics significantly. The methods utilized in these studies are
      described herein.

PMID- 19763955
TI  - Depletion and mutation of topoisomerase II in animal cells.
AB  - Eukaryotic type II topoisomerases (Topo II) are implicated in a wide range of
      cellular processes. Cells in which Topo II protein has been specifically depleted
      or mutated provide powerful systems for analysing the normal in vivo functions of
      Topo II proteins and for assessing their roles in various chemotherapy regimens.
      Summarised here are the ways in which Topo II has been depleted or mutated in
      animal cells and the type of information gleaned. The cell lines generated are
      tabulated and represent a useful resource for further in vivo studies of Topo II
      function, one that we expect to grow in size and utility in the coming years.

PMID- 19763956
TI  - Microfluidic techniques for the analysis of bacterial chemotaxis.
AB  - Anton van Leeuwenhoek first observed bacterial motility in the seventeenth
      century, and Wilhelm Pfeffer described bacterial chemotaxis in the late
      nineteenth century. A number of methods, briefly summarized here, have been
      developed over the years to quantify the motility and chemotaxis of bacteria, but
      none of them is totally satisfactory. In this chapter, we describe two new assays
      for chemotaxis that are based on microfabrication and microfluidic techniques.
      With easily culturable and manipulated bacteria like Escherichia coli,
      fluorescent labeling of the cells with green fluorescent protein (GFP) or red
      fluorescent protein (RFP) provides a convenient method for visualizing cells and
      differentiating two strains in the same experiment. The methods can be extended
      to environmental samples and mixed bacterial populations with suitable
      modifications of the optical recording system. The methods are equally useful for
      studying random motility, attractant chemotaxis, or repellent chemotaxis. The
      microfluidic system also provides a straightforward way to enrich for mutants
      that lose or gain responses to individual chemicals. The same approaches can
      presumably be used to isolate bacteria from environmental samples that respond,
      or do not respond, to particular chemicals or mixtures of chemicals.

PMID- 19763957
TI  - Prokaryotic phototaxis.
AB  - Microorganisms have various mechanisms at their disposal to react to (changes in)
      their ambient light climate (i.e., intensity, color, direction, and degree of
      polarization). Of these, one of the best studied mechanisms is the process of
      phototaxis. This process can be described as a behavioral migration-response of
      an organism toward a change in illumination regime. In this chapter we discuss
      three of these migration responses, based on swimming, swarming, and twitching
      motility, respectively. Swimming motility has been studied using a wide range of
      techniques, usually microscopy based. We present a detailed description of the
      assays used to study phototaxis in liquid cultures of the phototrophic organisms
      Halobacterium salinarum, Halorhodospira halophila, and Rhodobacter sphaeroides
      and briefly describe the molecular basis of these responses. Swarming and
      twitching motility are processes taking place at the interface between a solid
      phase and a liquid or gas phase. Although assays to study these processes are
      relatively straightforward, they are accompanied by technical complications,
      which we describe. Furthermore, we discuss the molecular processes underlying
      these forms of motility in Rhodocista centenaria and Synechocystis PCC6803.
      Recently, it has become clear that also chemotrophic organisms contain
      photoreceptor proteins that allow them to respond to their ambient light climate.
      Surprisingly, light-modulated motility responses can also be observed in the
      chemotrophic organisms Escherichia coli and Acinetobacter calcoaceticus. In the
      light-modulated surface migration not only "che-like" signal transduction
      reactions may play a role, but in addition processes as modulation of gene
      expression and even intermediary metabolism.

PMID- 19763958
TI  - Photoorientation in photosynthetic flagellates.
AB  - Motile microorganisms react to a host of external stimuli, including light,
      gravity, the magnetic field of the Earth as well as thermal and chemical
      gradients, in their habitat in order to select a niche suitable for survival and
      reproduction. Several forms of light-induced behavior have been described in
      microorganisms including phototaxis, photophobic responses, and photokinesis.
      Other functions of photoreceptors are regulation of development and entrainment
      of circadian rhythms. Basically five types of photoreceptor molecules have been
      identified in microorganisms: BLUF proteins, cryptochromes, phototropins,
      phytochromes, and rhodopsins. The photoreceptors can control light-activated ion
      channels or activated enzymes. The responses to the different stimuli in their
      habitat can be connected in a complex network of signal transduction chains.

PMID- 19763959
TI  - Dictyostelium slug phototaxis.
AB  - Dictyostelium slugs are able to respond to environmental stimuli in an extremely
      sensitive and efficient way. This enables a slug to migrate to more favourable
      locations for formation of fruiting bodies and dispersal of spores. Phototaxis is
      a readily assayed phenotype and reflects the interactions of environmental
      stimuli with morphogenetic signalling systems controlling the movement of the
      slug. The methods for assaying phototaxis are described here. Qualitative
      phototaxis tests are described and can be used for rapid screening of potential
      mutants or effects of pharmacological agents. These tests are simple to conduct
      yet care must be taken in order to avoid the effects of high cell density which
      can be misleading when interpreting results. Quantitative phototaxis tests can be
      performed with known cell densities of amoebae which ensures that any effects
      seen are caused by the mutation or pharmacological agent and not simply due to
      differences in cell densities.

PMID- 19763960
TI  - Electrotaxis and wound healing: experimental methods to study electric fields as
      a directional signal for cell migration.
AB  - Electric fields were measured at human skin wounds over one and half centuries
      ago. Modern techniques have verified and greatly extended our understanding of
      the existence of endogenous wound electric fields. In virtually all wounds
      studied, disruption of an epithelial layer instantaneously generates endogenous
      electric fields. As electric fields have the intrinsic property of being
      vectorial, it has long been proposed that these fields may serve as a directional
      signal guiding cell migration in wound healing. We have established several
      experimental systems to study the guidance effects and mechanisms of electric
      fields on cell migration. Most types of cells migrate directionally in a small
      electric field, a phenomenon called galvanotaxis/electrotaxis. Remarkably,
      electric fields of strength equal to those detected at in vivo wounds direct cell
      migration and override some other well-accepted coexistent guidance cues such as
      contact inhibition. The naturally occurring endogenous electric fields therefore
      may be an important signaling mechanism that regulates directional cell movement
      in vivo. Applied electric fields may have a potential clinical role in guiding
      cell migration in wound healing. The magnitude and direction of the electric
      field can be more precisely and quickly changed than most other guidance cues
      such as chemical cues. Application of electric fields thus offers a robust
      experimental system for study of directional cell migration with extensive
      flexibility. We present a brief review of the background and describe the
      experimental system for studying electrotaxis.

PMID- 19763961
TI  - Chemotropism during yeast mating.
AB  - Virtually all eukaryotic cells can grow in a polarized fashion in response to
      external signals. Cells can respond to gradients of chemoattractants or
      chemorepellents by directional growth, a process referred to as chemotropism. The
      budding yeast Saccharomyces cerevisiae undergoes chemotropic growth during
      mating, in which two haploid cells of opposite mating type grow toward one
      another. We have shown that mating pheromone gradients are essential for
      efficient mating in yeast and have examined the chemotropism defects of different
      yeast mutants. Two methods of assessing the ability of yeast strains to respond
      to pheromone gradients are presented here.

PMID- 19763962
TI  - Group migration and signal relay in Dictyostelium.
AB  - The ability of cells to migrate directionally in gradients of chemoattractant is
      a fundamental biological response that is essential for the survival of the
      social amoebae Dictyostelium discoideum. In Dictyostelium, cAMP is the most
      potent chemoattractant and the detection, synthesis, and degradation of cAMP is
      exquisitely regulated. Interestingly, as Dictyostelium cells migrate
      directionally, they do so in a head-to-tail fashion, forming characteristic
      streams. This group behavior is acquired through the relay of the cAMP signals to
      neighboring cells. This chapter describes experimental procedures used to obtain
      synchronized populations of chemotactically competent cells and to assess their
      streaming behavior. In addition, we provide a detailed account of the method used
      to measure the ability of chemoattractants to directly stimulate adenylyl cyclase
      activity. Together, these techniques provide a way to combine cell biological and
      biochemical approaches to the study of signal relay.

PMID- 19763963
TI  - Quantitative analysis of distal tip cell migration in C. elegans.
AB  - Correct distal tip cell (DTC) migration in the nematode C. elegans requires
      sensing soluble and matrix cues, remodeling extracellular matrix, and signaling
      through conserved integrin and netrin pathways. The DTC executes a complex path
      and coordinates its migration with the developmental stages of larval
      morphogenesis. This chapter outlines a method for investigating DTC migration in
      C. elegans using feeding RNA interference (RNAi) and light microscopy. To deplete
      a candidate gene of interest, nematode eggs are added to plates seeded with RNAi
      inducing bacterial lawns. The animals hatch and begin to eat the RNAi bacteria,
      releasing dsRNA and causing the targeted gene to be depleted during larval
      development. Positions of migratory cells are monitored in larvae and young
      adults using differential interference contrast (DIC) and epifluorescence
      microscopy.

PMID- 19763964
TI  - Inflammation and wound healing in Drosophila.
AB  - Cell motility is a widely researched and clinically relevant process that has
      primarily been investigated using cell culture models. While these in vitro
      assays are useful in allowing for high-resolution analysis of cell movement,
      there will always be questions surrounding the physiological relevance of
      studying cell migration on artificial 2-dimensional substrates. Therefore, a
      number of groups in recent years have started developing alternative systems,
      either ex vivo or in vivo, to begin extrapolating our knowledge surrounding cell
      motility to actual developmental and disease processes. One such example exploits
      the translucence of Drosophila embryos, and the genetic tractability of this well
      characterized model organism, to understand the cellular and molecular events
      surrounding inflammation and wound healing. Laser ablation of a small patch of
      embryonic epithelium in the Drosophila embryo results in a repair process that
      can be timelapse imaged in its entirety as the epithelial hole is sealed shut.
      Additionally, Drosophila macrophages can be imaged as they rapidly respond and
      chemotax to these sites of damage in a process reminiscent of the vertebrate
      inflammatory response. In both cases the imaging is of a spatial and temporal
      resolution approaching that which can be obtained from in vitro systems, making
      the Drosophila embryo an ideal model to begin dissecting the genetic control of
      cell migration during wound healing and inflammation in an in vivo setting.

PMID- 19763965
TI  - Neutrophil motility in vivo using zebrafish.
AB  - Zebrafish have emerged as a powerful model organism to study neutrophil
      chemotaxis and inflammation in vivo. Studies of neutrophil chemotaxis in animal
      models have previously been hampered both by the limited number of specimens
      available for analysis and by the need for invasive procedures to perform
      intravital microscopy. Due to the transparency and cell permeability of zebrafish
      embryos these limitations are circumvented, and the zebrafish system is amenable
      to both live time-lapse imaging of neutrophil chemotaxis and for screening of the
      effects of chemical compounds on the inflammatory response in vivo. Here, we
      describe methods to analyze neutrophil-directed migration toward wounds using
      both fixed embryos by myeloperoxidase activity assay, and live embryos by time
      lapse microscopy. Further, methods are described for the evaluation of the
      effects of chemical compounds on neutrophil motility and the innate immune
      responses in zebrafish embryos.

PMID- 19763966
TI  - Chemotaxis in neutrophil-like HL-60 cells.
AB  - Asymmetric localization of intracellular proteins and signals directs movement
      during axon guidance, endothelial cell invasion, and immune cell migration. In
      these processes, cell movement is guided by external chemical cues in a process
      known as chemotaxis. In particular, leukocyte migration in the innate immune
      system has been studied in the human neutrophil-like cell line (HL-60). Here, we
      describe the maintenance and transfection of HL-60 cells and explain how to
      analyze their behavior with two standard chemotactic assays. Finally, we
      demonstrate how to fix and stain the actin cytoskeleton of polarized cells for
      fluorescent microscopy imaging.

PMID- 19763967
TI  - Chemokine receptor dimerization and chemotaxis.
AB  - A broad array of biological responses ranging from cell polarization, movement,
      immune and inflammatory responses, as well as prevention of HIV-1 infection, are
      triggered by the chemokines, a family of structurally related chemoattractant
      proteins that bind to specific seven-transmembrane receptors linked to G
      proteins. Although it was initially believed that chemokine receptors act as
      monomeric entities, it has now been shown that they function as oligomers.
      Chemokine receptor homo- and heterodimers are found on the cell membrane; binding
      to their ligands stabilizes specific receptor conformations and activates
      distinct signaling cascades. Thorough analysis of the conformations adopted by
      the receptors at the membrane is therefore a prerequisite for understanding the
      function of these inflammatory mediators. For study of the chemokine receptor
      conformations at the cell surface, we focus here on conventional biochemical and
      genetic methods, as well as on new imaging techniques such as those based on
      resonance energy transfer; we also evaluate in vitro and in vivo methods to
      determine certain chemokine receptor functions.

PMID- 19763968
TI  - Intravital two-photon imaging of adoptively transferred B lymphocytes in inguinal
      lymph nodes.
AB  - Intravital two-photon imaging allows the observation of immune cells in intact
      organs of live animals in real time. Recently, several studies using two-photon
      microscopy have detailed the motility of mouse B and T lymphocyte within lymph
      nodes and have shown a dependence upon chemokine receptor signaling for the basal
      velocity of the cells. For, example, T cells from Gnia2 (-/-)mice, deficient in
      the heterotrimer G-protein G alpha subunit G(alpha i2) have markedly impaired
      chemokine-triggered chemotaxis. In vivo these cells have reduced motility and
      impaired positioning within lymph nodes. Gnia2 (-/-) B cells exhibit similar
      defects. In addition, B cells from Rgs1 (-/-) mice, deficient in a major negative
      regulator of G(alpha i), have a more robust motility than do wild-type B cells.
      Here, we describe procedures for visualizing the behavior of fluorescently
      labeled and adoptively transferred B lymphocytes within the inguinal lymph node
      of live mice.

PMID- 19763969
TI  - Breast cancer cell movement: imaging invadopodia by TIRF and IRM microscopy.
AB  - Invadopodia are hair-like membrane protrusions projecting from the ventral side
      of the plasma membrane of tumor cells invading into an extracellular matrix
      (ECM). Formation of invadopodia and phagocytosis of partially degraded ECM is
      correlated with invasiveness of cancer cells. Many proteins associated with actin
      rich punctae associated with invadopodia have been identified. However, the
      dynamic temporal and spatial relationship of invadopodia-related proteins and the
      mechanisms required for invadopodia formation remain largely unknown. Total
      Internal Reflection Fluorescence (TIRF) microscopy provides a powerful tool to
      directly visualize the dynamic membrane transportation of invadopodia-related,
      GFP-tagged proteins and to simultaneously monitor invadopodia formation by
      observation of localized degradation and phagocytosis of fluorescently labeled
      gelatin. Cell-substratum contacts can be visualized using a related technique,
      Interference Reflection Microscopy (IRM). In this chapter, we provide detailed
      methodologies to monitor the dynamic localizations of c-Src-eGFP using two-color
      TIRF microscopy along with IRM to simultaneously visualize translocation of c-Src
      eGFP and invadopodia formation by degradation of AlexaFluor 568-labeled gelatin.

PMID- 19763970
TI  - In vivo assay for tumor cell invasion.
AB  - We describe an in vivo invasion assay that enables the collection of invasive
      cells from the primary tumor. In addition to determination of the endogenous,
      unstimulated invasive properties of cells in vivo, the assay can take advantage
      of the chemotactic properties of cancer cells. Microneedles are filled with a
      mixture of extracellular matrix components such as Matrigel with or without a
      chemoattractant such as EGF, and then introduced into the primary tumor of a rat
      or mouse that is generated either by orthotopic injection of carcinoma cell lines
      or by a transgene such as polyoma Middle T. Over the course of 4 h the invasive
      cell population enters the needles while the animal is kept under anesthesia. At
      the end of the collection time, the invasive cells are extruded from the
      microneedles and can be analyzed in terms of the number and type of cells that
      invade in response to defined stimuli. By including pharmacological inhibitors in
      the needle, signaling pathways contributing to in vivo invasion can also be
      identified. This assay leads to a better understanding of the cell types and
      signaling involved in the tumor microenvironment, and has the potential to be
      applied to a variety of in vivo models.

PMID- 19763971
TI  - Quantitative studies of neuronal chemotaxis in 3D.
AB  - During development a variety of cell types are guided by molecular concentration
      gradients to form tissues and organ systems. In the nervous system, the migration
      and neuronal pathfinding that occurs during development is organized and driven
      by "guidance cues." Some of these cues are substrate bound or nondiffusible,
      while many are diffusible and form gradients within the developing embryo to
      guide neurons and neurites to their appropriate destination. There have been many
      approaches used to discover and characterize the multitude of guidance cues,
      their cognate receptors, and how these cues and receptors are regulated to
      achieve the highly detailed connections found in the nervous system. Here we
      present a method for creating precisely controlled gradients of molecular factors
      within a three-dimensional culture environment. The method is based on a non
      contact mediated delivery of biomolecules to the surface of a collagen gel. The
      factors are printed in a pattern on the top of a gel containing the tissue or
      cell type of interest embedded in the gel. The formation of the gradient is
      dependent upon the diffusion of the printed molecule in the gel. The
      concentration of the factor within the gel becomes independent of depth rapidly,
      and the gradient becomes smooth on a similar time scale. The gradients formed can
      remain relatively stable for a day or more. Moreover, the steepness and molar
      concentration of tropic or trophic factors within the gradient can be controlled.

PMID- 19763972
TI  - Assays for chemotaxis and chemoattractant-stimulated TorC2 activation and PKB
      substrate phosphorylation in Dictyostelium.
AB  - Chemotaxis is a highly coordinated biological system where chemoattractants
      trigger multiple signal transduction pathways which act in concert to bring about
      directed migration. A signaling pathway acting through PIP(3), which accumulates
      at the leading edge of the cell, has been extensively characterized. However,
      chemotaxis still remains in cells depleted of PIP(3), suggesting there are PIP(3)
      independent pathways. We have identified a pathway involving TorC2-PKBR1 as well
      as another containing PLA2 activity that act in parallel with PIP(3). Activation
      of PKBR1, a myristoylated Protein Kinase B homolog, is dependent on TorC2
      (Rapamycin-insensitive Tor complex 2) kinase but is completely independent of
      PIP(3). In response to chemoattractant, PKBs rapidly phosphorylate at least eight
      proteins, including Talin B, PI4P 5-kinase, two RasGefs, and a RhoGap. These
      studies help to link the signaling pathways to specific effectors and provide a
      more complete understanding of chemotaxis.

PMID- 19763973
TI  - Biochemical responses to chemoattractants in Dictyostelium: ligand-receptor
      interactions and downstream kinase activation.
AB  - Dictyostelium discoideum is one of the most facile eukaryotic systems for the
      study of chemotactic response to secreted chemical ligands. Dictyostelium grow as
      individual cells, using bacteria and fungi as primary nutrient sources; during
      growth, Dictyostelium moves directionally toward folate, a bacterial byproduct.
      Upon nutrient depletion Dictyostelium initiates a multicellular development
      program characterized by the production and secretion of cAMP. Cell surface
      receptors specifically recognize extracellular cAMP, which serves as both a
      morphogen to promote development and a chemoattractant to organize
      multicellularity. We discuss several approaches for the study of ligand-receptor
      interaction, with focus on affinity class determination and quantification of
      ligand binding sites (i.e., receptors) per cell. We further present examples for
      the application of biochemical assays to characterize the ligand-induced kinase
      activation of PI3K, GSK3, and ERK2.

PMID- 19763974
TI  - Quantifying in vivo phosphoinositide turnover in chemotactically competent
      Dictyostelium cells.
AB  - Phosphoinositide (PI) signalling is one of multiple signalling cascades involved
      in chemotaxis in Dictyostelium discoideum. PI signalling comprises a complex
      interaction of multiple enzymes, each with multiple phospholipid substrates and
      thus products, often relying upon several enzymes in series to produce a signal.
      PI turnover, controlled by both kinases and phosphatases, is also rapidly
      triggered and spatially constricted. This complexity makes understanding acute
      regulation of these signalling components problematic. However, the ubiquitous
      and extensive roles of phospholipids, including phosphatidylinositol-4,5
      diphosphate (PI(4,5)P(2)), in cell signalling and developmental processes make
      understanding the production of these compounds of great importance. We have
      shown the acute reduction of PI phosphorylation in response to a widely used
      bipolar disorder and epilepsy treatment, valproic acid, as a potential
      therapeutic role for the drug using chemotactically competent Dictyostelium. Here
      we describe a means for measuring acute in vivo phospholipid labelling in
      Dictyostelium.

PMID- 19763975
TI  - In vivo measurements of cytosolic calcium in Dictyostelium discoideum.
AB  - The involvement of calcium signalling during chemotaxis in Dictyostelium
      discoideum is well documented. Spatiotemporal increases of intracellular calcium
      ([Ca(2+)](i)) have been observed within seconds of stimulation with the
      chemoattractants folic acid and cAMP. This rise in [Ca(2+)](i) localises to the
      rear cortex of the cell (J. Cell Sci. 109:2673-2678, 1996) and has been found to
      be not essential for chemotaxis, but likely to be involved in fine tuning of
      chemotactic responses (EMBO J. 19:4846-4854, 2000). Measurements of cytosolic
      Ca(2+) ([Ca(2+)](c)) responses have involved the use of different Ca(2+) probes
      including ectopically expressed aequorin (a Ca(2+)-sensitive photoprotein), the
      fluorescent dye fura-2-dextran and the radioisotope (45)Ca(2+). The aequorin
      method (J. Cell Sci. 110:2845-2853, 1997) offers nonperturbing, real-time
      measurement of cytosolic free Ca(2+) in suspensions of cells, but the low levels
      of light emission preclude measurements on individual cells. Fura-2 imaging (Cell
      Calcium 22:65-74, 1997; Eur. J. Cell Biol. 58:172-181, 1992; Biochem. J. 332:541
      548, 1998; BMC Cell Biol. 6:13, 2005) has the advantage of allowing Ca(2+)
      responses to be observed in individual cells so that the subcellular localisation
      of the response and differences amongst individual cells can be observed. However
      data collection is more labour intensive, much smaller numbers of cells are
      sampled, the cells are unavoidably damaged physically during loading and the time
      resolution (s) is much less than that provided by the aequorin method (ms).
      (45)Ca(2+) uptake assays (Cell Biol. Int. Rep. 2:71-79, 1978; J. Cell Biol.
      112:103-110, 1991) allow measurement of Ca(2+) influx from the medium by cell
      suspensions with a time resolution of the order of seconds. Radioactive Ca(2+)
      uptake measurements are unsullied by but equally do not provide information about
      Ca(2+) efflux, intracellular Ca(2+) release or sequestration or changes in
      cytosolic free Ca(2+) levels.

PMID- 19763976
TI  - Chemokine receptor signaling and HIV infection.
AB  - The primary function of HIV-1 binding to its chemokine coreceptors is to mediate
      fusion and viral entry. However, it has been known that this interaction also
      triggers a variety of signaling cascades. It is likely that the virus-mediated
      signaling events may facilitate viral infection in various settings where the
      cellular conditions need to be primed. This has been exemplified recently in our
      findings that HIV-1 employs envelope-CXCR4 interaction to activate a cellular
      actin depolymerization factor, cofilin, to support viral latent infection of
      resting CD4 T cells. Activation of cofilin promotes the cortical actin dynamics
      that are critical for viral intracellular migration across the static cortical
      actin barrier in resting T cells.

PMID- 19763977
TI  - Spatiotemporal stimulation of single cells using flow photolysis.
AB  - Quantitative studies of chemotactic signaling require experimental techniques
      that can expose single cells to chemical stimuli with high resolution in both
      space and time. Recently, we have introduced the method of flow photolysis (Anal.
      Chem. 79:3940-3944, 2007), which combines microfluidic techniques with the
      photochemical release of caged compounds. This method allows us to tailor
      chemical stimuli on the length scale of individual cells with subsecond temporal
      resolution. In this chapter, we provide a detailed protocol for the setup of flow
      photolysis experiments and exemplify this versatile approach by initiating
      membrane translocation of fluorescent fusion proteins in chemotactic
      Dictyostelium discoideum cells.

PMID- 19763978
TI  - Spatiotemporal regulation of Ras-GTPases during chemotaxis.
AB  - Many eukaryotic cells can elicit intracellular signaling relays to produce
      pseudopodia and move up to the chemoattractant gradient (chemotaxis) or move
      randomly in the absence of extracellular stimuli and nutrients (random movement).
      A precise spatiotemporal regulation of Ras-GTPases, such as Ras and Rap, is
      crucial to induce pseudopodia formation and cellular adhesion during the
      chemotaxis and random movement. Here, we describe biochemical and real-time
      imaging methods for using Dictyostelium to understand the signaling events
      important for chemotaxis and random cell movement. The chapter includes (1) a
      biochemical method to assess Ras and Rap1 activation in response to
      chemoattractant, (2) an imaging method to detect endogenous Ras and Rap1
      activation in moving cells, and (3) a simultaneous imaging method to decipher the
      precise order and localization of these signaling events. With a combination of
      powerful Dictyostelium genetics, these methods will facilitate to elucidate a
      dynamic activation of Ras proteins and their inter relay with other signaling
      molecules during chemotaxis and random movement.

PMID- 19763979
TI  - FRAP analysis of chemosensory components of Dictyostelium.
AB  - Dictyostelium discoideum is a useful cell model for studying protein-protein
      interactions and deciphering complex signaling pathways similar to those found in
      mammalian systems. Many of these interactions were analyzed using classical in
      vitro biochemical techniques. However, with the accessibility of fluorescently
      tagged proteins, extensive protein networks are now being mapped out in living
      cells using a variety of microscopic techniques. One such technique, fluorescent
      recovery after photobleaching (FRAP), has been used in Dictyostelium to
      investigate a number of cellular processes including actin and cytoskeleton
      dynamics during chemotaxis and cytokinesis (J. Muscle Res. Cell Motil. 23:639
      649, 2002; Biophys. J. 81:2010-2019, 2001; Mol. Biol. Cell 16:4256-4266, 2005),
      to follow trafficking of proteins to organelles such as the membrane, nucleus,
      and endoplasmic reticulum (Development 130:797-804, 2003; J. Cell Biol. 154:137
      146, 2001), and to understand the role of proteins in cell adhesion during
      motility and division (Mol. Biol. Cell 18:4074-4084, 2007; J. Cell Sci. 120:4302
      4309, 2007). FRAP is a powerful tool that should provide a vast amount of
      information on the mobility of a number of proteins, not only in Dictyostelium,
      but in many organisms. This study will lay out the methods of conducting FRAP
      experiments in Dictyostelium and discuss the large amount of knowledge which can
      be gained by adopting this as a common technique.

PMID- 19763980
TI  - Monitoring dynamic GPCR signaling events using fluorescence microscopy, FRET
      imaging, and single-molecule imaging.
AB  - How a eukaryotic cell translates a small concentration difference of a
      chemoattractant across the length of its surface into highly polarized
      intracellular responses is a fundamental question in chemotaxis. Chemoattractants
      are detected by G-protein-coupled receptors (GPCRs). Binding of chemoattractants
      to GPCRs induces the dissociation of heterotrimeric G-proteins into G alpha and G
      betagamma subunits, which in turn, activate downstream signaling networks. To
      fully understand the molecular mechanisms of chemotaxis, it is essential to
      quantitatively measure the dynamic changes of chemoattractant concentrations
      around cells, activation of heterotrimeric G-proteins, and the mobility of GPCR
      and G-protein subunits in the cell membrane. Here, we outline fluorescence
      imaging methods including Forster resonance energy transfer (FRET) imaging and a
      single-molecule analysis that allow us to measure the dynamic properties of GPCR
      signaling in single live cells.

PMID- 19763981
TI  - Imaging actin cytoskeleton dynamics in Dictyostelium chemotaxis.
AB  - This chapter will focus on responses that the chemoattractant cyclic AMP elicits
      in the motility system of Dictyostelium. These cells can be permanently
      transfected to express cytoskeleton-associated proteins tagged with fluorescent
      proteins. Multiple proteins that are distinguishable by the excitation and
      emission spectra of their tags can be simultaneously expressed. This makes it
      possible to relate the spatial and temporal patterns of their chemoattractant
      induced translocation to each other in one cell by a single recording. Since
      actin polymerization in live cells progresses with velocities of about 3
      microm/s, high image frequencies and short acquisition times in the millisecond
      range are required. Techniques of total internal reflection fluorescence (TIRF)
      and spinning-disc confocal microscopy provide appropriate temporal and spatial
      resolution for the analysis of actin dynamics.

PMID- 19763982
TI  - Analysis of actin assembly by in vitro TIRF microscopy.
AB  - Since directed movement toward an extracellular chemoattractant requires rapid
      and continuous reorganization of the actin cytoskeleton to form complex
      structures such as a protruding lamellipodium, it is of great interest to analyze
      and understand the individual contribution of proteins specifically involved in
      this process. Over the last decade, enormous progress has been made toward
      understanding the versatile molecular mechanisms underlying actin-based cell
      motility and the regulation of site-specific F-actin assembly and disassembly. In
      spite of this wealth of knowledge and due to the constant discovery of novel
      regulatory factors, many questions remain to be answered. In this chapter, we
      describe a powerful method that allows to study the effects of actin-binding
      proteins on the assembly of single filaments by in vitro total internal
      reflection fluorescence (TIRF) microscopy using purified proteins and
      fluorescently labeled actin.

PMID- 19763983
TI  - Single-molecule imaging techniques to visualize chemotactic signaling events on
      the membrane of living Dictyostelium cells.
AB  - In this chapter, we describe methods to monitor signaling events at the single
      molecule level on the membrane of living cells by using total internal reflection
      fluorescence microscopy (TIRFM). The techniques provide a powerful tool for
      elucidating the stochastic properties of signaling molecules involved in
      chemotaxis of the cellular slime mold Dictyostelium discoideum. Taking cAMP
      receptor 1 (cAR1) as an example of a target protein for single-molecule imaging,
      we describe the experimental setup of TIRFM, a method for labeling cAR1 with a
      fluorescent dye, and a method for investigating the receptor's lateral mobility.
      We discuss how the developmental progression of cells modulates both cAR1
      behavior and the phenotypic variability in cAR1 mobility for different cell
      populations.

PMID- 19763984
TI  - Imaging B-cell receptor signaling by single-molecule techniques.
AB  - B-cell activation initiates antibody responses against pathogens. Recent imaging
      of B cells in vivo shows that B cells move rapidly through lymphoid tissues to
      search for antigens captured on the surfaces of antigen-presenting cells.
      Recognition of antigens by the B-cell antigen receptor (BCR) leads to
      microclustering of the BCR and the initiation of intracellular signaling that
      prompts the B cells to stop and form immunological synapses with the antigen
      presenting cells. Although the biochemical signaling pathways downstream of the
      BCR that mediate these events are becoming better characterized, the initial
      molecular steps in BCR microclustering and activation remain elusive. In part,
      this is because the dynamics of the cell-cell contact makes the observation of
      the antigen-induced changes in the BCR technically challenging. Here we review
      single-molecule imaging techniques that help to provide new information on the
      molecular behavior of small populations of the BCR as they initiate intracellular
      signaling in a dynamically moving B cell. The techniques are generally applicable
      to the study of a broad range of membrane receptors involved in cell-cell
      contacts.

PMID- 19763985
TI  - Light microscopy to image and quantify cell movement.
AB  - For decades, Dictyostelium discoideum has been an efficacious and attractive
      model system for the study of cell motility, primarily because cells become
      highly motile during the transition from growth phase to aggregation competence
      and because the haploid genome is readily amenable to mutation. These crawling
      amoebae, as well as other motile cells such as polymorphonuclear neutrophils
      (PMNs), extend pseudopodia, retract pseudopodia, and translocate across a
      substratum even in the absence of chemoattractant. This phenomenon, referred to
      as basic motile behavior, has been investigated in Dictyostelium through analysis
      of cytoskeletal mutants. Likewise, many chemotactic signal transduction pathways
      and networks have been inferred from studies of Dictyostelium mutants. However,
      before concluding from mutational analyses that a particular molecule or protein
      plays a role in chemotaxis, it is imperative to first precisely define its
      contribution, if any, to basic motile behavior. Here, we describe two-dimensional
      and three-dimensional technologies that can be coupled with 2D and 3D Dynamic
      Image Analysis System (2D and 3D-DIAS) software for the analysis of cell
      motility, shape changes, pseudopod formation, and localization of tagged
      molecules during basic motile behavior. In addition, we describe a method to
      analyze the 3D trajectories of microspheres attached to the surface of crawling
      Dictyostelium cells. We include information on microscopy, image acquisition
      techniques, and computer hardware that could be reproduced in a typical
      laboratory setting for motion analysis using 2D and 3D-DIAS software. Finally, we
      highlight features available in DIAS that have proven insightful in identifying
      defects in basic motile behavior exhibited by various cytoskeletal and putative
      signal transduction mutants.

PMID- 19763986
TI  - Mathematics of experimentally generated chemoattractant gradients.
AB  - Many eukaryotic cells move in the direction of a chemical gradient. Several
      assays have been developed to measure this chemotactic response, but no complete
      mathematical models of the spatial and temporal gradients are available to
      describe the fundamental principles of chemotaxis. Here we provide analytical
      solutions for the gradients formed by release of chemoattractant from a point
      source by passive diffusion or forced flow (micropipettes) and gradients formed
      by laminar diffusion in a Zigmond chamber. The results show that gradients
      delivered with a micropipette are formed nearly instantaneous, are very steep
      close to the pipette, and have a steepness that is strongly dependent on the
      distance from the pipette. In contrast, gradients in a Zigmond chamber are formed
      more slowly, are nearly independent of the distance from the source, and resemble
      the temporal and spatial properties of the natural cAMP wave that Dictyostelium
      cells experience during cell aggregation.

PMID- 19763987
TI  - Modeling spatial and temporal dynamics of chemotactic networks.
AB  - When stimulated by chemoattractants, eukaryotic cells respond through a
      combination of temporal and spatial dynamics. These responses come about because
      of the interaction of a large number of signaling components. The complexity of
      these systems makes it hard to understand without a means of systematically
      generating and testing hypotheses. Computer simulations have proved to be useful
      in testing conceptual models. Here we outline the steps required to develop these
      models.

PMID- 19763988
TI  - Computational modeling of signaling networks for eukaryotic chemosensing.
AB  - The task of developing and simulating computational models of signaling networks
      for eukaryotic chemosensing confronts the modeler with several challenges: (1)
      The stimuli that initiate the cellular responses one wishes to study are provided
      by extracellular concentration gradients. This means that the computational model
      must have a spatially resolved representation of extracellular molecular
      concentrations. (2) The intracellular responses consist of the generation of
      intracellular accumulations and/or translocations of signaling molecules,
      requiring spatially resolved computational representations of the simulated
      cells. (3) The signaling networks responsible for eukaryotic chemosensing
      comprise a multitude of components acting as receptors, adaptors, (lipid- and
      protein-) kinases (including GTPases), (lipid- and protein-) phosphatases, and
      molecule types used by others for membrane attachment. Models of such signaling
      networks may become quite complicated, unless one wishes to rely on abstract
      functional modules with certain input-output characteristics as modeling
      "shortcuts" replacing subnetworks of biological signaling molecules. In this
      chapter, we describe how modelers can use a modeling tool ("simmune") developed
      to facilitate the design and simulation of detailed computational models of
      signaling pathways (for eukaryotic chemosensing here), thereby avoiding the
      technical difficulties typically associated with building and simulating such
      quantitative models.

PMID- 19763989
TI  - A RIKILT yeast estrogen bioassay (REA) for estrogen residue detection in urine of
      calves experimentally treated with 17beta-estradiol.
AB  - 17beta-Estradiol is one of the most powerful sex steroids illegally used in
      bovine production. The objective of this study was to evaluate the application
      and the specificity of the RIKILT yeast estrogen bioassay (REA) for the detection
      of molecules with estrogenic activities in the urine of calves experimentally
      treated with anabolics. Four groups of six calves each received an injection of
      17beta-estradiol intramuscularly (group B), androsterone and gliburide (group A),
      and testosterone (group C) molecules at different dosage for 40 days. Group D was
      the control. The ability of the REA test to detect estrogenic activity in urine
      samples from all animals was assessed. All estrogen-treated animals (group B)
      showed as being positive up to 7 days after administration of the highest dosage
      of 17beta-estradiol, while the other three groups showed as being negative. The
      identity of estrogenic molecules in the urine of group B (17beta-estradiol,
      17alpha-estradiol) was confirmed by gas chromatography-mass spectrometry (GC/MS).
      This is the first time the REA test has been applied to detect 17beta-estradiol
      in the urine of calves treated with the hormone in vivo. The technique may offer
      an advantageous laboratory method for the veterinary surveillance of illegal
      steroid use.

PMID- 19763990
TI  - Review of the use of phytosterols as a detection tool for adulteration of olive
      oil with hazelnut oil.
AB  - Adulteration of virgin olive oil with less expensive oils such as hazelnut oil is
      a serious problem for quality control of olive oil. Detection of the presence of
      hazelnut oil in olive oil at low percentages (<20%) is limited with current
      official standard methods. In this review, various classes of phytosterols in
      these two oils are assessed as possible markers to detect adulterated olive oil.
      The composition of 4-desmethyl- and 4-monomethylsterols is similar in both oils,
      but the 4,4'-dimethylsterols differ. Lupeol and an unknown (lupane skeleton)
      compound from 4,4'-dimethylsterols are exclusively present in hazelnut oil and
      can be used as markers via GC-MS monitoring to detect adulteration at levels as
      low as 2%. The phytosterol classes need to be separated and enriched by a
      preparative method prior to analysis by GC or GC/MS; these SPE and TLC methods
      are also described in this review.

PMID- 19763991
TI  - Effect of extrusion conditions and lipoxygenase inactivation treatment on the
      physical and nutritional properties of corn/cowpea (Vigna unguiculata) blends.
AB  - The influence of lipoxygenase inactivation and extrusion cooking on the physical
      and nutritional properties of corn/cowpea (Vigna unguiculata) blends was studied.
      Corn was blended in an 80:15 proportion with cowpea flour treated to inactivate
      lipoxygenase (CI) or non-inactivated cowpea flour (CNI). Extrusion variables were
      temperature (150 degrees C, 165 degrees C and 180 degrees C) and moisture (15%,
      17% and 19%). Based on their physical properties, the 165 degrees C/15% corn:CNI,
      and 165 degrees C/15% corn:CI, and 150 degrees C/15% corn:CI blends were chosen
      for nutritional quality analysis. Extrudate chemical composition indicated high
      crude protein levels compared with standard corn-based products. With the
      exception of lysine, essential amino acids content in the three treatments met
      FAO requirements. Extrusion and lipoxygenase inactivation are promising options
      for developing corn/cowpea extruded snack products with good physical properties
      and nutritional quality.

PMID- 19763992
TI  - The beneficial effect of Mediterranean dietary patterns on dietary iron
      utilization in male adolescents aged 11-14 years.
AB  - The effects of a diet based on Mediterranean patterns on iron bioavailability and
      iron status in adolescents were studied. The study was divided into two periods:
      basal period, in which 21 male adolescents consumed their habitual diet (basal
      diet); and nutritional intervention period, during which an experimental diet
      based on the Mediterranean model was consumed. Dietary iron utilization was
      studied by means of iron intake and iron output in faeces and urine, and iron
      status was analysed in fasting blood samples collected at the end of each period.
      No differences in total iron intake were found between diets, but consumption of
      the experimental diet increased iron absorption and retention compared with the
      basal diet. Biochemical parameters related to iron metabolism did not vary after
      the intervention period, although serum ferritin tended to increase. Therefore, a
      diet based on Mediterranean dietary patterns may improve dietary iron utilization
      during adolescence and may prevent iron deficiency.

PMID- 19763993
TI  - Pragmatic comprehension deficit in Parkinson's disease.
AB  - Recognizing the specific speech act (Searle, 1969) that a speaker performs with
      an utterance is a fundamental feature of pragmatic competence. However, little is
      known about neurocognitive mediation of speech act comprehension. The present
      research examined the extent to which people with Parkinson's disease (PD)
      comprehend specific speech acts. In the first experiment, participants read
      conversational utterances and then performed a lexical decision task (decide
      whether a target string of letters was a word). Consistent with past research,
      nonimpaired participants performed this task more quickly when the target string
      was the speech act associated with the preceding utterance. In contrast, people
      with PD did not demonstrate this effect, suggesting that speech act activation is
      slowed or is not an automatic component of comprehension for people with PD. In a
      second study, participants were given unlimited time to indicate their
      recognition of the speech act performed with an utterance. PD participants were
      significantly poorer at this task than were control participants. We conclude
      that a previously undocumented language disorder exists in PD and that this
      disorder involves a selective deficit in speech act comprehension. Frontostriatal
      systems (the systems impaired in PD) likely contribute to normal speech act
      comprehension.

PMID- 19763994
TI  - Bilateral limbic system destruction in man.
AB  - We report here a case study of a rare neurological patient with bilateral brain
      damage encompassing a substantial portion of the so-called "limbic system." The
      patient, Roger, has been studied in our laboratory for over 14 years, and the
      current article presents his complete neuroanatomical and neuropsychological
      profiles. The brain damage occurred in 1980 following an episode of herpes
      simplex encephalitis. The amount of destroyed neural tissue is extensive and
      includes bilateral damage to core limbic and paralimbic regions, including the
      hippocampus, amygdala, parahippocampal gyrus, temporal poles, orbitofrontal
      cortex, basal forebrain, anterior cingulate cortex, and insular cortex. The right
      hemisphere is more extensively affected than the left, although the lesions are
      largely bilateral. Despite the magnitude of his brain damage, Roger has a normal
      IQ, average to above-average attention, working memory, and executive functioning
      skills, and very good speech and language abilities. In fact, his only obvious
      presenting deficits are a dense global amnesia and a severe anosmia and ageusia.
      Roger's case presents a rare opportunity to advance our understanding of the
      critical functions underlying the human limbic system, and the neuropsychological
      and neuroanatomical data presented here provide a critical foundation for such
      investigations.

PMID- 19763996
TI  - Attention and visual orienting in siblings, schizophrenic patients, and controls:
      impairment in attentional disengagement.
AB  - Visual orienting tasks reveal an impaired disengagement of attention in
      schizophrenia. We explored visual orientation in 20 schizophrenia patients (SZ),
      20 full siblings (FS), and 20 controls (C) using a cued target detection (gap vs.
      no gap) and a choice reaction time task. SZ but not FS had longer reaction time
      with comparable reactions to warning. In contrast to C, SZ and FS did not display
      a significant gap effect. The disengagement deficit in schizophrenia patients and
      their siblings provides arguments for altered early attention mechanisms (in
      schizophrenic patients and their nonpsychotic relatives).

PMID- 19763998
TI  - Flower drinking and masculinity in Taiwan.
AB  - This study explores the role of the hostess club culture in the creation and
      maintenance of masculinity in Taiwan. The article focuses on flower drinking (the
      consumption of alcohol in bars, often integrated with prostitution), which is a
      common practice in Taiwan. Data were obtained from 58 in-depth interviews with
      men from a variety of occupations and social backgrounds (mean age = 38.50, SD =
      11.00) and 73 questionnaires administered to soldiers (mean age = 21.00, SD =
      1.10). Findings indicated that demonstration of skill at flower drinking and
      facility with the related social etiquette are important channels for male
      bonding that were central to the mid- to upper-class participants' professional
      development. Flower drinking also provided a method of discriminating men from
      other men through their choices of why and where to go and how to behave while
      there. Specific ways that Taiwanese masculinity differs from Western and from
      Japanese masculinity, and support for the continuing relevance of the traditional
      Confucian ideal of masculinity, wen-wu, are discussed.

PMID- 19763997
TI  - The semantic relatedness of cue-intention pairings influences event-based
      prospective memory failures in older adults with HIV infection.
AB  - HIV infection and aging are each independently associated with prospective memory
      (ProM) impairment, which increases the risk of poor functional outcomes,
      including medication non-adherence. The incidence and prevalence of HIV infection
      among older adults has increased in recent years, thereby raising questions about
      the combined effects of these risk factors on ProM. In the present study, 118
      participants were classified into four groups on the basis of HIV serostatus and
      age (i.e., <or=40 years and >or=50 years). Results showed significant additive
      effects of HIV and aging on event-based ProM, with the greatest deficits evident
      in the older HIV+ group, even after controlling for other demographic factors and
      potential medical and psychiatric confounds. Event-based ProM impairment was
      particularly apparent in the older HIV+ group on trials for which the retrieval
      cue and intention were not semantically related. Worse performance on the
      semantically unrelated cue-intention trials was associated with executive
      dysfunction, older age, and histories of immunocompromise in the older HIV+
      cohort. These data suggest that older HIV-infected adults are significantly less
      proficient at engaging the strategic encoding and retrieval processes required to
      a execute a future intention when the cue is unrelated to the intended action,
      perhaps secondary to greater neuropathological burden in the prefrontostriatal
      systems critical to optimal ProM functioning.

PMID- 19763999
TI  - A dose of fructose induces oxidative stress during endurance and strength
      exercise.
AB  - This study sought to compare the time course changes in oxidative state and
      glycemic behavior when glucose or glucose plus fructose are consumed before
      endurance and strength exercise. After two weeks on a controlled diet, 20
      physically trained males ingested an oral dose of glucose or glucose plus
      fructose, 15 min before starting a moderate-intensity 30-min session of endurance
      or strength exercise. The combination resulted in four randomized interventions:
      glucose or glucose plus fructose + endurance exercise and glucose or glucose plus
      fructose + strength exercise, which were implemented consecutively in random
      order at 1-week intervals. Plasma concentration of lipoperoxides, oxidized LDL,
      reduced glutathione, catalase and glycemia were determined at baseline, during
      exercise and acute recovery. Following the ingestion of glucose plus fructose,
      lipoperoxides, catalase and reduced glutathione depletion were significantly
      higher than following consumption of glucose, for both endurance and strength
      exercise (P < 0.05). Oxidized LDL-c was higher after glucose plus fructose than
      after glucose alone in endurance exercise (P < 0.05). There was no difference in
      the glycemic peak between glucose plus fructose and glucose ingestion in
      endurance exercise trials. In strength exercise, the post-absorptive glycemic
      peak was less when the participants ingested glucose plus fructose than glucose
      (P < 0.05), and a second peak was found in the recovery phase of this group (P <
      0.05). In conclusion, the addition of fructose to a pre-exercise glucose
      supplement triggers oxidative stress.

PMID- 19764000
TI  - Ubiquitous computing in sports: A review and analysis.
AB  - Ubiquitous (pervasive) computing is a term for a synergetic use of sensing,
      communication and computing. Pervasive use of computing has seen a rapid increase
      in the current decade. This development has propagated in applied sport science
      and everyday life. The work presents a survey of recent developments in sport and
      leisure with emphasis on technology and computational techniques. A detailed
      analysis on new technological developments is performed. Sensors for position and
      motion detection, and such for equipment and physiological monitoring are
      discussed. Aspects of novel trends in communication technologies and data
      processing are outlined. Computational advancements have started a new trend -
      development of smart and intelligent systems for a wide range of applications -
      from model-based posture recognition to context awareness algorithms for
      nutrition monitoring. Examples particular to coaching and training are discussed.
      Selected tools for monitoring rules' compliance and automatic decision-making are
      outlined. Finally, applications in leisure and entertainment are presented, from
      systems supporting physical activity to systems providing motivation. It is
      concluded that the emphasis in future will shift from technologies to intelligent
      systems that allow for enhanced social interaction as efforts need to be made to
      improve user-friendliness and standardisation of measurement and transmission
      protocols.

PMID- 19764001
TI  - The impact of technology on sporting performance in Olympic sports.
AB  - To assess the effect of technology on sport, the performance statistics for four
      disciplines were analysed: the 100-m sprint, pole vault, javelin, and cycling.
      The concept of a performance improvement index was developed to allow comparison
      between athletes and between sports with a higher index indicating a greater
      improvement in the sport. The following performance improvement indices were
      found: 100-m sprint, 24% over 108 years; pole vault, 86% over 94 years; javelin,
      95% over 76 years; 4-km individual pursuit, 35% over 32 years; one-hour cycling
      record, 221% over 111 years. Around 4% of the index for the sprint was attributed
      to tighter, aerodynamic clothing, suggesting that general athletic improvement in
      sprint-type events has been around 20%. Technological developments in simple
      equipment such as the pole vault or javelin were seen to affect the index by
      around 30%, while the index associated with aerodynamic improvements in the one
      hour record was around 100%. It is concluded that the performance improvement
      index could be extended to amateur as well as elite sport where distance or time
      is used as a measure of performance.

PMID- 19764002
TI  - Isolation and identification of phenolic compounds from Hypericum richeri Vill.
      and their antioxidant capacity.
AB  - The chemical composition and free radical scavenging properties of the MeOH
      extract of Hypericum richeri and its subsequent CHCl(3), n-BuOH, EtOAc and
      aqueous extracts were investigated. Four quercetin-3-O-glycosides, three
      myricetin-3-O-glycosides, 3-O- and 5-O-caffeoylquinic acid, quercetin, I3,II8
      biapigenin, pseudohypericin and hypericin were identified. The constituents of
      the extracts were quantified using HPLC-DAD (high-performance liquid
      chromatography-diode array detector). Isolation of the compounds from n-BuOH and
      EtOAc extracts was conducted by column chromatography. Antioxidant capacity of
      the extracts was evaluated by superoxide radical and ABTS?(+) scavenging assays
      and inhibition of lipid peroxidation. The EtOAc extract of H. richeri was the
      most potent antioxidant in all experiments. Free radical scavenging compounds
      were identified by HPLC-DPPH? (high-performance liquid chromatography-2,2
      diphenyl-1-picrylhydrazyl) post-column derivatisation method, where all phenolic
      compounds except I3,II8-biapigenin exhibited radical scavenging properties. This
      is the first report of the presence of myricetin-3-O-rutinoside, myricetin-3-O
      galactoside, myricetin-3-O-glucoside, 5-O-caffeoylquinic acid and I3,II8
      biapigenin in H. richeri.

PMID- 19764003
TI  - Cytotoxic clerodane diterpenoids from the leaves of Polyalthia longifolia.
AB  - The ethanolic extract of Polyalthia longifolia var. pendula was fractionated to
      get a hexane-soluble residue, which led to the isolation of four clerodane
      diterpenes: (-)-3alpha,16alpha-dihydroxycleroda-4(18),13(14)Z-dien-15,16-olide
      (1), (-)-3beta,16alpha-dihydroxycleroda-4(18), 13(14)Z-dien-15,16-olide (2), (-)
      16alpha-hydroxycleroda-3,13(14)Z-dien-15,16-olide (3) and (-)-16-oxocleroda
      3,13(14)E-dien-15-oic acid (4). Diterpene 1 is a new compound, while 2 is
      reported for first time from this plant. Both 1 and 2 were tested for their
      growth inhibitory activity on four cancer cell lines in vitro. IC(50) values
      suggest that they are effective as cytotoxic agents.

PMID- 19764004
TI  - Mutagenesis and genetic characterisation of amylolytic Aspergillus niger.
AB  - Aspergillus niger FCBP-198 was genetically modified for its ability to reveal
      extra cellular alpha-amylase enzyme activity. From 76 efficient mutants isolated
      after ultraviolet (UV) irradiation, An-UV-5.6 was selected as the most efficient
      UV mutant, with 76.41 units mL(-1) of alpha-amylase activity compared to wild
      (34.45 units mL(-1)). In case of ethyl methane sulphonate (EMS), among 242
      survivors, 74 were assayed quantitatively and An-Ch-4.7 was found to be the most
      competent, as it exhibited a three-fold increase in alpha-amylase activity (89.38
      units mL(-1)) than the parental strain. Genetic relationships of the mutants of
      A. niger FCBP-198 were analysed with a randomly amplified polymorphic DNA
      polymerase chain reaction (RAPD-PCR). Results obtained from the comparison
      between genotypes of A. niger FCBP-198 showed differences in the sizes and
      numbers of amplified fragments per primer for each isolate. The dendrogram showed
      that genotypes An-Ch-4.7 and An-Ch-4.2 were distinctly classified into one
      category, while the isolates An-UV-5.6, An-UV-5.1 and A. niger FCBP-198 have the
      nearest genetic relationship. The five isolates from A. niger FCBP-198 genotypes
      shared an average of 65% bands.

PMID- 19764005
TI  - Effect of Citrullus colocynthis Schrad fruits on testosterone-induced alopecia.
AB  - Alopecia is a psychologically distressing phenomenon. Androgenetic alopecia (AGA)
      is the most common form of alopecia, which affects millions of men and women
      worldwide, and is an androgen driven disorder. Here, the Citrullus colocynthis
      Schrad fruit is evaluated for hair growth activity in androgen-induced alopecia.
      Petroleum ether extract of C. colocynthis was applied topically for its hair
      growth-promoting activity. Alopecia was induced in albino mice by testosterone
      administration intramuscularly for 21 days. Its inhibition by simultaneous
      administration of extract was evaluated using follicular density, anagen/telogen
      (A/T) ratio and microscopic observation of skin sections. Finasteride (5alpha
      reductase inhibitor) solution was applied topically and served as positive
      control. Petroleum ether extract of C. colocynthis exhibited promising hair
      growth-promoting activity, as reflected from follicular density, A/T ratio and
      skin sections. The treatment was also successful in bringing a greater number of
      hair follicles in anagenic phase than the standard finasteride. The result of
      treatment with 2 and 5% petroleum ether extracts were comparable to the positive
      control finasteride. The petroleum ether extract of C. colocynthis and its
      isolate is useful in the treatment of androgen-induced alopecia.

PMID- 19764006
TI  - Cytotoxic and antiviral activities of aporphine alkaloids of Magnolia grandiflora
      L.
AB  - Bioassay guided fractionation of the methanol extract of Magnolia grandiflora L.
      (Magnoliaceae) leaves led to the isolation and characterisation of four aporphine
      alkaloids, magnoflorine, lanuginosine, liriodenine and anonaine. The
      cytotoxicities of the pure compounds magnoflorine and lanuginosine were
      determined in a cell viability assay with the tumour cell lines Hela (cervix
      tumour cell line), HEPG2 (hepatocellular carcinoma cell line) and U251 (brain
      tumour cell line). Magnoflorine was more cytotoxic (IC(50) 0.4 microg mL(-1))
      than lanuginosine (IC(50) 2.5 microg mL(-1)) against HEPG2 in comparison with the
      standard doxorubacin (IC(50) 0.27 microg mL(-1)). In addition, magnoflorine and
      lanuginosine exhibited cytotoxicity against U251, with IC(50) of 7 and 4 microg
      mL(-1), respectively. The two compounds were found to be inactive against the
      Hela cancer cell. On the other hand, the methanol extract showed high antiviral
      activity against the herpes simplex virus (HSV-1), 76.7% inhibition at 1.1 microg
      mL(-1), whereas the extract exhibited a moderate antiviral activity against
      poliovirus type-1 (47% inhibition at the same concentration). This chemical and
      biological investigation has not been studied previously.

PMID- 19764007
TI  - Lower limb influence on standing arm-cranking ('grinding').
AB  - Standing arm-cranking ('grinding') is predominantly an upper-body exercise,
      however, the contribution of the legs to this activity is unknown. The purpose of
      the study was to examine the influence of normal lower-limb movement on
      physiological strain during arm-cranking. Eight elite professional America's Cup
      grinders performed two exercise trials, on an adjustable standing arm-crank
      ergometer with SRM powercrank, in a cross-over design. Each trial comprised of
      two 5-min stages at the same work rate ( approximately lactate threshold) with
      the knee joint splinted or normal movement available. Vertical ground reaction
      forces (VGRF) and knee joint angle were determined from two force plates and
      sagittal plane video, respectively. Work rate was identical for the two
      conditions (246 (14) vs. 246 (13) W, p=0.7). Knee joint range of motion and
      unilateral VGRF amplitude were greater during normal compared with splinted arm
      cranking (both p<0.01). There was no difference in VO2 (p=0.2) between the two
      conditions, however, there was greater VCO2 (8%, p=0.001), RER (11%, p<0.001),
      V(E) (17%, p<0.001) and HR (7 (3) beats.min(-1), p<0.001) during splinted
      compared with normal arm-cranking. Furthermore, the rise in BLa was greater after
      splinted than normal arm-cranking (4.8 (0.8) vs. 3.7 (1.0) mmol.L(-1), p=0.04).
      These data suggest that the lower-limbs play an integral role in standing arm
      cranking, and restricted leg movement markedly affects the cardiovascular and
      metabolic responses to this activity.

PMID- 19764008
TI  - [Impairments of vision- and health-related quality of life in stroke patients
      with homonymous visual field defects depend on severity of visual function loss].
AB  - BACKGROUND AND PURPOSE: Little is known about whether and to what extent health-
      and vision-related quality of life in stroke patients with visual field defects
      is influenced by the severity of visual function loss and which quality of life
      is achieved compared to healthy control persons. PATIENTS/MATERIALS AND METHODS:
      Results of the National Eye Institute-Visual Functioning Questionnaire (NEI-VFQ)
      and the Medical Outcome Study Short-Form 36 Health Survey (SF-36) of 177 first
      stroke patients with visual field defects were compared with scores of age- and
      sex-matched healthy reference persons. The influence of visual field loss,
      perimetric data, reduced visual acuity and demographic variables on NEI-VFQ and
      SF-36 scores were estimated by analyses of variance. RESULTS: First stroke
      patients showed worse results in 11/12 NEI-VFQ and in 6/8 SF-36 subscales when
      compared to healthy controls. The factor "intact central visual field" influenced
      9/12 NEI-VFQ subscales (F-range 3.16 - 14.11; all p < 0.05), but only one SF-36
      scale (F = 3.15; p < 0.05). Patients with larger intact visual fields, shorter
      reaction times in the visual field test and better visual acuity reached higher
      NEI-VFQ and SF-36 scores. Male patients reported worse scores for SF-36 subscale
      General Health Perceptions than female patients (F = 8.61; p = 0.004), but no
      differences in vision-related quality of life due to the factor gender could be
      detected. CONCLUSIONS: Patients with visual field defects showed considerable
      reductions in vision- and health-related quality of life compared to healthy
      control persons. These were mainly influenced by variables of visual functioning
      such as size of intact visual field, reaction times or visual acuity. The size of
      the intact central visual field influenced vision-related quality of life rather
      than health-related quality of life.

PMID- 19764009
TI  - In-vivo examples of flow patterns with the fast vector velocity ultrasound
      method.
AB  - PURPOSE: Conventional ultrasound methods for acquiring color flow images of the
      blood motion are limited by a relatively low frame rate and are restricted to
      only giving velocity estimates along the ultrasound beam direction. To circumvent
      these limitations, the Plane Wave Excitation (PWE) method has been proposed.
      MATERIAL AND METHODS: The PWE method can estimate the 2D vector velocity of the
      blood with a high frame rate. Vector velocity estimates are acquired by using the
      following approach: The ultrasound is not focused during the ultrasound
      transmission, and a full speckle image of the blood can be acquired for each
      pulse emission. The pulse is a 13 bit Barker code transmitted simultaneously from
      each transducer element. The 2D vector velocity of the blood is found using 2D
      speckle tracking between segments in consecutive speckle images. Implemented on
      the experimental scanner RASMUS and using a 100 CPU linux cluster for post
      processing, PWE can achieve a frame of 100 Hz where one vector velocity sequence
      of approximately 3 sec, takes 10 h to store and 48 h to process. In this paper a
      case study is presented of in-vivo vector velocity estimates in different complex
      vessel geometries. RESULTS: The flow patterns of six bifurcations and two veins
      were investigated. It was shown: 1. that a stable vortex in the carotid bulb was
      present opposed to other examined bifurcations, 2. that retrograde flow was
      present in the superficial branch of the femoral artery during diastole, 3. that
      retrograde flow was present in the subclavian artery and antegrade in the common
      carotid artery during diastole, 4. that vortices were formed in the sinus pockets
      behind the venous valves in both antegrade and retrograde flow, and 5. that
      secondary flow was present in various vessels. CONCLUSION: Using a fast vector
      velocity ultrasound method, in-vivo scans have been recorded where complex flow
      patterns were visualized in greater detail than previously visualized by
      conventional color flow imaging techniques.

PMID- 19764010
TI  - Changes in the histomorphometric and biomechanical properties of the proximal
      femur of ovariectomized rat after treatment with the phytoestrogens genistein and
      equol.
AB  - The isoflavonoids found in soy have attracted great interest as dietary
      phytoestrogens that might be effective for postmenopausal hormone replacement
      therapy. Special attention has been devoted to the hormonal effects of various
      isoflavonoids, like genistein (GEN) and daidzein's (DAID) potent metabolite,
      equol (EQ). Here we aimed to investigate the short-term effects of genistein and
      equol on the proximal femur of ovariectomized (OVX) rats. Forty-eight, 3-month
      old female Sprague-Dawley rats were ovarectomized; after eight weeks the
      bilateral osteotomy and osteosynthesis (OS) of their tibiae was performed and the
      rats were randomly divided into the following four groups: OVX control group (C),
      treated with estradiol-17beta (E2) -benzoate (E; daily intake 0.086 mg/d per
      animal), genistein (GEN; daily intake 12.7 mg/d per animal) and equol (EQ; daily
      intake 4.65 mg/d per animal). At 5 weeks postoperatively (OS), the breaking test
      was performed on the trochanteric region of femur. Additionally,
      histomorphometric assessment, and trabecular and cortical bone microstructure
      analyses were performed. The relative gain of body weight (BW) in the EQ (24 %)
      group was significantly (p < 0.05) lower than in the C (33 %) and GEN (30 %)
      groups. After treatment for 5 weeks, the maximal load (F(max)) and yield load
      (yL) were higher (p < 0.05 for the weight-adapted results) in the E (188.4 N
      resp. 113.1 N) and EQ (177.3 N resp. 112 N) groups as compared to C (162.8 N
      resp. 109.1 N) and GEN (165.7 N resp. 108.8 N). In the histomorphometric tests
      the E- (trabecular area (Tb.Ar) = 74.93 %, trabecular nodes/mm(2) (N.Nd/mm(2)) =
      48.65) and EQ-treated (Tb.Ar = 63.13 %, N.Nd/mm(2) = 43.72) animals showed
      significant improvement with regard to Tb.Ar and trabecular connectivity
      (N.Nd./mm(2)) in comparison to C (Tb.Ar = 46.84, N.Nd/mm(2) = 31.86) and GEN
      (Tb.Ar = 48.22 %, N.Nd/mm(2) = 34.15). There were no differences in relative
      cortical width (Ct.Wi) among the four groups. The treatment with EQ resulted in
      improved biomechanical and histomorphometric properties as compared to the
      treatment with GEN. Thus, of the studied substances, EQ seems to be a possible
      alternative to hormone replacement therapy, but further studies are needed.

PMID- 19764011
TI  - Individual and combined effect of meso-2,3-dimercaptosuccinic acid and allicin on
      blood and tissue lead content in mice.
AB  - It has been shown that garlic and its main bioactive component, allicin, as
      natural chelating agents can reduce blood and tissue lead content in animal
      models. In this study the effect of allicin, alone or combined with meso-2,3
      dimercaptosuccinic acid (DMSA), in decreasing lead content of blood and tissues
      of mice was evaluated. Swiss albino mice were exposed to 1000 ppm of lead in
      water for 35 days and then placed in various treatment groups including groups
      administered oral allicin, DMSA, or their combination. The concentrations of lead
      in blood, kidney, liver, bone and brain were measured using atomic absorption
      spectrophotometry. Both, allicin and DMSA decreased the blood and tissue lead
      concentration. There was an additive effect of the combined administration of
      allicin and DMSA in reducing bone lead. No side effect was observed in all
      treated groups. Combined use of DMSA and allicin seems to be a better choice in
      the treatment of chronic lead intoxication.

PMID- 19764012
TI  - The effects of the diterpenes isolated from the Brazilian brown algae Dictyota
      pfaffii and Dictyota menstrualis against the herpes simplex type-1 replicative
      cycle.
AB  - We describe in this paper that the diterpenes 8,10,18-trihydroxy-2,6
      dolabelladiene ( 1) and (6 R)-6-hydroxydichotoma-4,14-diene-1,17-dial ( 2),
      isolated from the marine algae DICTYOTA PFAFFII and D. MENSTRUALIS, respectively,
      inhibited HSV-1 infection in Vero cells. We initially observed that compounds 1
      and 2 inhibited HSV-1 replication in a dose-dependent manner, resulting in EC
      (50) values of 5.10 and 5.90 microM, respectively, for a multiplicity of
      infection (MOI) of 5. Moreover, the concentration required to inhibit HSV-1
      replication was not cytotoxic, resulting in good selective index (SI) values.
      Next, we found that compound 1 sustained its anti-herpetic activity even when
      added to HSV-1-infected cells at 6 h after infection, while compound 2 sustained
      its activity for up to 3 h after infection, suggesting that these compounds
      inhibit initial events during HSV-1 replication. We also observed that both
      compounds were incapable of impairing HSV-1 adsorption and penetration. In
      addition, the tested molecules could decrease the contents of some HSV-1 early
      proteins, such as UL-8, RL-1, UL-12, UL-30 and UL-9. Our results suggest that the
      structures of compounds 1 and 2, Brazilian brown algae diterpenes, might be
      promising for future antiviral design.

PMID- 19764014
TI  - [Pneumonia--researcher finds a replacement for antibiotics].

PMID- 19764013
TI  - [Pneumonia--pneumonia risk from acid-suppressive medications?].

PMID- 19764016
TI  - [Pediatrics/infection epidemiology - RSV-infection in children under 5].

PMID- 19764017
TI  - [Interview -- drug legislation -- reporting unexpected adverse drug reactions].

PMID- 19764018
TI  - [Respiratory tract infections--prescription of antibiotics for respiratory tract
      infections].

PMID- 19764019
TI  - Mandibuloacral dysplasia type A in childhood.
AB  - Mandibuloacral dysplasia type A (MADA) is characterized by growth retardation,
      postnatal onset of craniofacial anomalies with mandibular hypoplasia, progressive
      acral osteolysis, and skin changes including mottled pigmentation, skin atrophy,
      and lipodystrophy. Owing to its slowly progressive course, the syndrome has been
      recognized in adults, and pediatric case reports are scarce. We present the
      clinical case of two children in whom the diagnosis of MADA was made at an
      unusually early age. A 5-year-old boy presented with ocular proptosis, thin nose,
      and short and bulbous distal phalanges of fingers. A 4-year-old girl presented
      with round face and chubby cheeks, thin nose, bulbous fingertips, and type A
      lipodystrophy. In both, a skeletal survey showed wormian bones, thin clavicles,
      short distal phalanges of fingers and toes with acro-osteolysis. Both children
      were found to be homozygous for the recurrent missense mutation, c.1580G>A,
      (p.R527H) in exon 9 of the LMNA gene. Thus, the phenotype of MADA can be manifest
      in preschool age; diagnosis may be suggested by short and bulbous fingertips,
      facial features, and lipodystrophy, supported by the finding of acral osteolysis,
      and confirmed by mutation analysis.

PMID- 19764020
TI  - 4.3-Mb triplication of 4q32.1-q32.2: report of a family through two generations.
AB  - Duplications of 4q31-qter have been rarely documented; moreover, triplications at
      this chromosomal region have never been described. Here we report a family
      through two generations (mother and three sons) with triplication of 4q32.1
      q32.2. Their characteristic features include: macrocephaly, a long midface,
      hypoplastic zygoma, wide nasal bridge, short nose, downslanting and small
      palpebral fissures, and small, low-set and squared-off ears. Among the three
      sons, two had Hirschsprung disease, and one had constipation at birth. The
      phenotype of triplication of 4q32.1-q32.2 appeared to be distinct from
      duplications of 4q31-qter.

PMID- 19764021
TI  - Partial ATRX gene duplication causes ATR-X syndrome.

PMID- 19764022
TI  - Floating-Harbor syndrome and intramedullary spinal cord ganglioglioma: case
      report and observations from the literature.
AB  - We report on a 5-year-old male with expressive language delay, developmental
      delay, short stature, and facial anomalies consistent with Floating-Harbor
      syndrome (FHS). In addition, he developed an intramedullary ganglioglioma. This
      is the first reported case of a tumor associated with FHS, and may represent an
      as yet undefined genetic link between spinal cord tumors and FHS, adding this
      syndrome to the growing list of disorders with a predisposition for tumor
      development.

PMID- 19764023
TI  - Confirmation of TFAP2A gene involvement in branchio-oculo-facial syndrome (BOFS)
      and report of temporal bone anomalies.
AB  - Branchio-oculo-facial syndrome (BOFS) is an autosomal-dominant condition
      characterized by three main features, respectively: branchial defects, ocular
      anomalies, and craniofacial defects including cleft lip and/or palate (CL/P). We
      report on one family with three affected, and two sporadic cases that have been
      found to carry missense mutations in the newly reported BOFS gene: TFAP2A. This
      report confirms the involvement of this transcription factor in this
      developmental syndrome with clinical variability. Moreover, we present CT scan
      temporal bone anomalies in the familial cases, related to branchial arch defects,
      highlighting the importance of radiological investigations for differential
      diagnosis.

PMID- 19764024
TI  - Apparent third patient with cutaneous mastocytosis, microcephaly, conductive
      hearing loss, and microtia.
AB  - Mastocytosis refers to a heterogeneous group of rare disorders characterized by
      an abnormal accumulation of mast cells in one or more organ systems. Cutaneous
      mastocytosis (CM) is the most frequent form in children and is characterized by
      hyperpigmented macules or papules symmetrically distributed over the trunk, and
      less so over the limbs, neck, and scalp. Two published articles have reported on
      unrelated girls presenting with mastocytosis, microcephaly, hearing loss, and
      hypotonia. Based on the original observation, this disorder was defined as CM
      with short stature, conductive hearing loss, and microtia (OMIM 248910). Here we
      report on a girl with similar manifestations who corroborates the existence of
      this rare disorder. CM, microcephaly, microtia, and/or hearing loss are the
      minimal diagnostic criteria. All the known patients were sporadic, but parental
      consanguinity in the first case argues for a possible autosomal-recessive
      inheritance.

PMID- 19764025
TI  - Tethered cord, corpus callosum abnormalities, and periventricular cysts in Wolf
      Hirschhorn syndrome. Report of two cases and review of the literature.
AB  - Wolf-Hirschhorn syndrome (4p-) is a rare disorder with characteristic physical
      findings. Neuroimaging findings are relatively scarce. We performed a literature
      search and found 22 reports of neuroimaging findings. We present findings in our
      two cases, each with the previously unreported finding of a tethered cord. The
      most common abnormalities were of the corpus callosum, occurring in 71% of all
      cases. There appears to be a high association in the syndrome between corpus
      callosal abnormalities and periventricular cysts formation in the first year of
      life. These cysts eventually fuse with the frontal horns during late infancy with
      enlargement of the frontal horns. Absence of other causes for periventricular
      cyst formation, such as perinatal distress, prematurity, or cytomegalovirus
      infection, appears to strengthen the association. With further studies,
      neuroimaging findings may eventually assist in the diagnosis of patients with
      Wolf-Hirschhorn syndrome.

PMID- 19764026
TI  - Genotype-phenotype correlations in VHL exon deletions.
AB  - Von Hippel-Lindau (VHL) syndrome is a dominantly inherited familial cancer
      syndrome caused by mutations in the VHL gene. VHL syndrome displays marked
      variation in expression and analysis of genotype-phenotype correlations have led
      to the concept of four subtypes of VHL syndrome (Types 1, 2A-C). Type 2 subtypes
      of VHL syndrome are characterized by the presence of pheochromocytoma and the
      three Type 2 subtypes are associated with differing risks of hemangioblastoma and
      renal cell carcinoma (RCC). Type 2 VHL syndrome is usually associated with
      surface missense mutations. Type 1 VHL syndrome is most commonly caused by
      germline exon deletions and truncating mutations and is characterized by
      susceptibility to hemangioblastomas and RCC but not pheochromocytoma. Recently,
      it has been suggested that large VHL gene deletions involving C3orf10 (HSPC300)
      might be associated with a low risk of RCC. We have reviewed the molecular and
      clinical characteristics of 127 individuals with germline VHL gene deletions.
      Large VHL gene deletions associated with a contiguous loss of C3orf10 were
      associated with a significantly lower lifetime risk of RCC than deletions that
      did not involve C3orf10. The risks of hemangioblastomas were similar in both
      groups. These results add to the growing body of evidence suggesting that
      patients with VHL syndrome caused by large VHL deletions that include C3orf10 may
      be designated as having a specific subtype (Type 1B) of the disorder.

PMID- 19764027
TI  - Progressive neurocognitive decline in two children with Dravet syndrome, de novo
      SCN1A truncations and different epileptic phenotypes.
AB  - Dravet syndrome, often caused by mutations of SCN1A-gene, presents with prolonged
      clonic, generalized or unilateral seizures often occurring with fever during the
      first year of life, followed by usually severe epilepsy. The EEG, normal at the
      outset, later shows generalized and focal epileptic activities. The psychomotor
      development deteriorates, but little is known about the time course of the
      cognitive impairment and its relationship with seizures severity. We describe
      here the progressive neurocognitive decline in two children (one male), carrying
      de novo SCN1A truncating mutations and presenting with different epileptic
      phenotypes. The children were longitudinally assessed from the ages of 11 and 23
      months until the age of 7 and 8 years, using the same scales to measure the
      developmental competence in various domains. Both had seizures during the first
      year of life, unilateral clonic in one and myoclonic in the other, but the
      subsequent epilepsy severity and the characteristics of the EEG diverged. One
      child had drug-resistant but rare generalized seizures and isolated EEG spike
      wave paroxysms, while the other developed extremely frequent clusters of
      polymorphic seizures and generalized plus multifocal EEG epileptic activities.
      MRI was normal in both. A clear developmental delay begun before the age of 2
      years in both children and the cognitive profile continued to worse, with some
      differences between different domains, irrespectively to the different course of
      their epileptic histories. Our observations are consistent with the hypothesis
      that SCN1A-mutations can be responsible not only for epilepsy, but also for early
      and progressive severe mental impairment.

PMID- 19764028
TI  - Czech dysplasia occurring in a Japanese family.
AB  - Czech dysplasia (OMIM 609162) is a recently established COL2A1 disorder
      characterized by normal height, early-onset osteoarthritis, platyspondyly, short
      metatarsals, and the absence of ophthalmological complications or cleft palate. A
      specific missense mutation (c.823C > T, R275C) in the exon 13 of the COL2A1 gene,
      coding for the triple helical domain of the alpha 1 chain of the type II
      collagen, has been linked to Czech dysplasia, which is quite a unique situation
      among the COL2A1 disorders. Since all of the 11 families and patients reported to
      date were of European ancestry, an ancient single origin of the R275C mutation
      was speculated about. Here we report on a Japanese family consisting of three
      patients with Czech dysplasia, each member showing valgus knees in addition to
      remarkably uniform manifestation of the clinical and radiological abnormalities.
      Mutation analysis documented the COL2A1 c.823C > T mutation in all affected
      individuals. In conclusion, this report provides novel evidence for the
      independent occurrence of Czech dysplasia among the populations.

PMID- 19764029
TI  - Complex contributions of Ets2 to craniofacial and thymus phenotypes of trisomic
      "Down syndrome" mice.
AB  - Ts65Dn mice have segmental trisomy for orthologs of about half of the genes on
      human chromosome 21, including Ets2. These mice develop anomalies of the cranial
      skeleton and thymus that parallel those in Down syndrome. Overexpression of the
      Ets2 transcription factor gene was posited to be sufficient to produce these
      craniofacial and thymus deficits in transgenic mice that constitutively
      overexpress a processed Ets2 transcript under a promiscuous promoter [Sumarsono
      et al. (1996); Nature 379:534-537; Wolvetang et al. (2003); Hum Mol Genet 12:247
      255]. Evaluation of trisomic mice with varying copy numbers of a properly
      regulated Ets2 gene indicated increased dosage of Ets2 was not sufficient to
      produce effects on thymus and most of the cranial anomalies seen in Ts65Dn mice.
      However, mesoderm-derived cranial skeletal elements are significantly more
      affected in Ts65Dn, Ets2(+/-) mice compared to Ts65Dn littermates suggesting a
      differential interaction of Ets2-related processes with mesoderm-derived and
      neural crest-derived formative tissues. Our results support the growing evidence
      for interactions among multiple genes contributing to developmental perturbations
      resulting in variation in complex Down syndrome phenotypes.

PMID- 19764030
TI  - Genetic and phenotypic heterogeneity in two novel cases of Waardenburg syndrome
      type IV.

PMID- 19764031
TI  - Clinical variability of Waardenburg-Shah syndrome in patients with proximal 13q
      deletion syndrome including the endothelin-B receptor locus.
AB  - Waardenburg-Shah syndrome (Waardenburg syndrome type IV-WS4) is an auditory
      pigmentary disorder that combines clinical features of pigmentary abnormalities
      of the skin, hair and irides, sensorineural hearing loss, and Hirschsprung
      disease (HSCR). Mutations in the endothelin-B receptor (EDNRB) gene on 13q22 have
      been found to cause this syndrome. Mutations in both alleles cause the full
      phenotype, while heterozygous mutations cause isolated HSCR or HSCR with minor
      pigmentary anomalies and/or sensorineural deafness. We investigated the status of
      the EDNRB gene, by FISH analysis, in three patients with de novo proximal 13q
      deletions detected at cytogenetic analysis and examined the clinical variability
      of WS4 among these patients. Chromosome 13q was screened with locus specific FISH
      probes and breakpoints were determined at 13q22.1q31.3 in Patients 1 and 3, and
      at 13q21.1q31.3 in Patient 2. An EDNRB specific FISH probe was deleted in all
      three patients. All patients had common facial features seen in proximal 13q
      deletion syndrome and mild mental retardation. However, findings related to WS4
      were variable; Patient 1 had hypopigmentation of the irides and HSCR, Patient 2
      had prominent bicolored irides and mild bilateral hearing loss, and Patient 3 had
      only mild unilateral hearing loss. These data contribute new insights into the
      pathogenesis of WS4.

PMID- 19764033
TI  - Severe neonatal spondylometaphyseal dysplasia in two siblings.
AB  - We report on two siblings with a severe neonatal form of spondylometaphyseal
      dysplasia (SMD). Similar cases have been reported in four publications. Analysis
      of pedigree data from the original and present families suggests an autosomal
      recessive mode of inheritance, although parental gonadal mosaicism is also
      possible. The similarities in the phenotype between our patients and
      spondyloepimetaphyseal dysplasia congenita (SEMDC) and spondyloepimetaphyseal
      dysplasia Strudwick (SEMDS) type, indicated that these patients could have a
      defect in the COL2A1 gene. Molecular analysis of genomic DNA of these patients
      excluded this gene. Another potential candidate gene PTHR1, was also analyzed in
      the selected regions and no mutation was found. This gene is probably causative
      in the Jansen type of SMD, which shares some phenotypic features with the
      siblings whom we documented. Our results indicate that a new candidate gene for
      the reported form of SMD should be sought.

PMID- 19764034
TI  - A girl with distinctive features of borderline high blood pressure, short
      stature, characteristic brachydactyly, and 11.47 Mb deletion in 12p11.21-12p12.2
      by oligonucleotide array CGH.

PMID- 19764032
TI  - Expanding CEP290 mutational spectrum in ciliopathies.
AB  - Ciliopathies are an expanding group of rare conditions characterized by
      multiorgan involvement, that are caused by mutations in genes encoding for
      proteins of the primary cilium or its apparatus. Among these genes, CEP290 bears
      an intriguing allelic spectrum, being commonly mutated in Joubert syndrome and
      related disorders (JSRD), Meckel syndrome (MKS), Senior-Loken syndrome and
      isolated Leber congenital amaurosis (LCA). Although these conditions are
      recessively inherited, in a subset of patients only one CEP290 mutation could be
      detected. To assess whether genomic rearrangements involving the CEP290 gene
      could represent a possible mutational mechanism in these cases, exon dosage
      analysis on genomic DNA was performed in two groups of CEP290 heterozygous
      patients, including five JSRD/MKS cases and four LCA, respectively. In one JSRD
      patient, we identified a large heterozygous deletion encompassing CEP290 C
      terminus that resulted in marked reduction of mRNA expression. No copy number
      alterations were identified in the remaining probands. The present work expands
      the CEP290 genotypic spectrum to include multiexon deletions. Although this
      mechanism does not appear to be frequent, screening for genomic rearrangements
      should be considered in patients in whom a single CEP290 mutated allele was
      identified.

PMID- 19764035
TI  - Genetic research on stored tissue samples from minors: a systematic review of the
      ethical literature.
AB  - The potential benefits of biobank research are well known. Also, the ethical
      implications of genetic research on stored tissue samples are well discussed in
      existing literature. The inclusion of tissue samples from minors may have
      significant scientific value. However, this inclusion raises specific ethical
      questions. We have performed a systematic search of the literature and found 21
      theoretical and empirical articles dealing with the issue. After review, we
      distilled five clusters of themes: consent, risks, benefits, return of results,
      and ownership. We have described the different components of these themes, as
      they occurred in the literature and have provided a discourse on the topic.

PMID- 19764036
TI  - Skeletal abnormalities in neurofibromatosis type 1: approaches to therapeutic
      options.
AB  - The skeleton is frequently affected in individuals with neurofibromatosis type 1,
      and some of these bone manifestations can result in significant morbidity. The
      natural history and pathogenesis of the skeletal abnormalities of this disorder
      are poorly understood and consequently therapeutic options for these
      manifestations are currently limited. The Children's Tumor Foundation convened an
      International Neurofibromatosis Type 1 Bone Abnormalities Consortium to address
      future directions for clinical trials in skeletal abnormalities associated with
      this disorder. This report reviews the clinical skeletal manifestations and
      available preclinical mouse models and summarizes key issues that present
      barriers to optimal clinical management of skeletal abnormalities in
      neurofibromatosis type 1. These concepts should help advance optimal clinical
      management of the skeletal abnormalities in this disease and address major
      difficulties encountered for the design of clinical trials.

PMID- 19764037
TI  - Fragile X prenatal analyses show full mutation females at high risk for mosaic
      Turner syndrome: fragile X leads to chromosome loss.
AB  - The fragile X mutation is an expansion of a CGG triplet repeat in the 5'
      untranslated region of the FMR1 gene. Expansion to >200 repeats (the "full
      mutation") silences FMR1 transcription and leads to the fragile X mental
      retardation syndrome in males and in some females. It also affects the structure
      of the mitotic chromosome as evidenced by a folate sensitive fragile site.
      Isolated cases of 45,X/46,XX (mosaic Turner syndrome) in full mutation females
      have been reported but an increased prevalence was not apparent from these
      reports. PCR and Southern analysis of the CGG repeat in 423 prenatal female
      samples identified 106 full mutation cases. Surprisingly five of these had
      45,X/4,6XX mosaicism while none of the other 317 female fetuses did. In two of
      the five cases >or=50% of the cells were reported to be 45,X and in the other
      three, <or=14%. We investigated the association of the full mutation and mosaic
      Turner syndrome using polymorphisms and single cell cloning to identify the X
      chromosome that was lost. Our analysis indicates that at least four of the five
      full mutation mosaicism cases were due to loss of the maternal, full mutation
      chromosome. These data indicate that 45,X/46,XX mosaicism is much more common
      than expected in fragile X full mutation females. Moreover, they suggest that the
      presence of the fragile X full mutation on a chromosome may predispose it to loss
      during mitosis, possibly due to the altered structure of the metaphase fragile X
      chromosome.

PMID- 19764038
TI  - Interstitial deletion 2p11.2-p12: further delineation.

PMID- 19764039
TI  - Detailed assessment of the ear in Cornelia de Lange syndrome: comparison with a
      control sample using the new dysmorphology guidelines.
AB  - The literature abounds with reports of malformation syndromes in which human
      external ears are variously described as dysplastic, abnormal, large/small, low
      set, typical, or in some way unusual. Rarely is the ear well illustrated or
      described in meaningful detail. With few exceptions, such as Down syndrome, there
      is no real understanding of the degree to which ear morphology is affected in a
      specific syndrome. This paper describes a retrospective attempt to apply the
      recently published Morphological Definitions of the ear to compare a control
      sample of convenience with a group of patients with Cornelia de Lange syndrome
      (CdLS) (all six papers in this issue are available online, open access at
      http://www3.interscience.wiley.com/journal/121641055/issue). Although this study
      has a number of limitations, it demonstrates that the method can be successfully
      applied and is capable of producing data that can be subjected to statistical
      analysis. The ears of the patients with CdLS were significantly different from
      the controls over a number of descriptors, the most significant of which included
      more frequent apparent posterior rotation, a shorter more serpiginous antihelical
      stem and sharper antihelical to inferior crus angle, a shorter crus helix, a more
      V-shaped incisura, and a smaller lobe.

PMID- 19764040
TI  - Increasing the sample size at interim for a two-sample experiment without Type I
      error inflation.
AB  - For the case of a one-sample experiment with known variance sigma2 =1, it has
      been shown that at interim analysis the sample size (SS) may be increased by any
      arbitrary amount provided: (1) The conditional power (CP) at interim is >= 50%
      and (2) there can be no decision to decrease the SS (stop the trial early). In
      this paper we verify this result for the case of a two-sample experiment with
      proportional SS in the treatment groups and an arbitrary common variance.
      Numerous authors have presented the formula for the CP at interim for a two
      sample test with equal SS in the treatment groups and an arbitrary common
      variance, for both the one- and two-sided hypothesis tests. In this paper we
      derive the corresponding formula for the case of unequal, but proportional SS in
      the treatment groups for both one-sided superiority and two-sided hypothesis
      tests. Finally, we present an SAS macro for doing this calculation and provide a
      worked out hypothetical example. In discussion we note that this type of trial
      design trades the ability to stop early (for lack of efficacy) for the
      elimination of the Type I error penalty. The loss of early stopping requires that
      such a design employs a data monitoring committee, blinding of the sponsor to the
      interim calculations, and pre-planning of how much and under what conditions to
      increase the SS and that this all be formally written into an interim analysis
      plan before the start of the study.

PMID- 19764041
TI  - Research continues into best ways to treat low-risk prostate cancer.

PMID- 19764042
TI  - Minority and women cancer patients report worse pain.

PMID- 19764044
TI  - Rate of T alleles and TT genotype at MTHFR 677C->T locus or C alleles and CC
      genotype at MTHFR 1298A->C locus among healthy subjects in Turkey: impact on
      homocysteine and folic acid status and reference intervals.
AB  - Methylenetetrahydrofolate reductase (MTHFR) is important for folate and
      homocysteine (Hcy) metabolism. MTHFR 677C->T and 1298A->C MTHFR are two most
      common mutations which can affect folate and total homocysteine (tHcy) status.
      This study was designed to determine the rate of MTHFR 677C->T and 1298A->C
      mutations, and their influence on serum folate, Hcy and vitamin B12 status and
      the reference intervals in 402 healthy Turkish adults. The rate of MTHFR 677C->T
      or 1298A->C mutations was 50.7% or 54.7%, respectively. The MTHFR 677C->T
      mutation-specific reference intervals for serum folate and tHcy were
      characterized by marked shifts in their upper limits. In homozygote subjects for
      MTHFR 677C->T serum folate concentration was lower and serum tHcy concentration
      was higher than those in the wild genotype; all subjects had lower serum folate
      and 54% of the subjects had higher tHcy concentrations than the cutoff values of
      <or=10 nmol/L and >or=12 micromol/L, respectively. Serum vitamin B12 status was
      similar in all genotypes. Serum tHcy concentrations were inversely correlated
      with serum folate and vitamin B12 concentrations in all genotypes. These data
      show that the rate of MTHFR 677C->T and 1298A->C mutations is very high in Turks
      and serum folate and tHcy status are impaired by these mutations.

PMID- 19764048
TI  - LC-MS of streptomycin following desalting of a nonvolatile mobile phase and pH
      gradient.
AB  - Streptomycin (SM) is composed of streptidine, streptose and N-methyl glucosamine
      sugar moieties. For the determination of SM and its related substances, an ion
      pair LC-UV detection method using a Supelcosil LC-ABZ column was developed
      previously. While analyzing commercial samples, several unknown compounds were
      detected. Most of these compounds are not yet characterized. In this study, the
      above LC method was coupled to MS for impurity profiling in a selected commercial
      sample. However, it could not be directly coupled to MS due to the presence of
      the nonvolatile salt, buffer and ion-pair reagent in the mobile phase. So, for
      structural characterization, each peak eluted from the nonvolatile eluent system
      was collected and transferred to MS after the desalting process. In total, 16
      compounds were studied, 15 compounds including 12 unknowns could be identified.

PMID- 19764049
TI  - Asymmetric flow field-flow fractionation of liposomes: 2. Concentration detection
      and adsorptive loss phenomena.
AB  - The applicability of different concentration detection methods for online
      quantification of liposomes upon asymmetric flow field-flow fractionation was
      investigated. Filter-extruded egg phosphatidylcholine liposomes of different size
      were used. Online quantification using a differential refractive index (dRI)
      detector was found feasible for relatively high sample loads in the magnitude of
      100 microg lipid (under the chosen fractionation conditions). UV-Vis detection of
      the turbidity of liposomes was ruled out as online detection method because
      turbidity increases with particle size and the signal is not only concentration
      but also particle-size dependent. Staining of liposomes by Rhodamine
      phosphatidylethanolamine or Sudan Red and subsequent online UV-Vis detection at
      the absorption maximum of the dye enabled quantification with much higher
      sensitivity than dRI detection. Furthermore analyte loss and carry-over phenomena
      upon repeated injection of varying liposome sample loads were studied using
      regenerated cellulose (RC) membranes as accumulation wall. It could be shown that
      RC membranes are prone to adsorption in case of very small sample loads (0.5
      microg). This effect may be overcome by pre-saturation of the membrane with
      sample loads of at least 2 microg. For higher sample loads adsorptive losses play
      a minor role. Recovery from pre-saturated membranes reached approximately 100%
      and carry-over was found negligible.

PMID- 19764050
TI  - Capillary electrophoresis with dual laser detection in separation of amplified
      fragment length polymorphism fragments.
AB  - We are presenting the application of CE technique with dual-channel LIF detection
      for the simultaneous separation of DNA fragments labeled with two different
      fluorescence dyes. The optimal conditions of the analysis were determined for the
      separation of amplified fragment length polymorphism (AFLP) fragments labeled
      with 5'-6-carboxyfluorescein (6-FAM) and the DNA size standard labeled with
      sulfoindocyanine succinimidyl ester (Cy-5). CE equipped with both argon ion and
      diode lasers is a good alternative for sequencers and might be applied in
      analyses of PCR products generated by various fingerprinting methods.

PMID- 19764051
TI  - Rapid screening of beta-adrenergic agents and related compounds in human urine
      for anti-doping purpose using capillary electrophoresis with dynamic coating.
AB  - This paper presents a capillary electrophoresis method, developed for the
      detection, in human urine, of beta-adrenergic agents and phenolalkylamines. The
      electrophoretic separation is achieved in less than 10 min and is based on the
      use of CEofix kit, for the dynamic capillary coating. The effects of accelerator
      buffer pH and separation voltage were investigated. The optimum buffer pH was
      found to be 2.5 for beta2-agonists and 6.2 for beta-blockers and phenoalkylamines
      with a separation voltage of 15 kV. Urine samples spiked with the compounds here
      studied were treated according to the standard procedure (SPE and evaporation to
      dryness) and analyzed by CE interfaced with an UV diode-array, set at 195 and 210
      nm. The quantitative validation results, obtained analyzing samples at three
      different concentrations, show a good precision of peak areas that do not exceed
      5% for intra-day assays and 10% for inter-day assays. Good linearity (r(2) >
      0.995) was obtained within the 50-500 ng/mL concentration range. The qualitative
      validation data show a relative migration times (MTs) variation lower than 1%.
      The analytes were clearly distinguishable in urine, with LOD and LOQ in the range
      of 10-80 and 40-100 ng/mL, respectively.

PMID- 19764052
TI  - Microwave extraction of essential oils from dried fruits of Illicium verum Hook.
      f. and Cuminum cyminum L. using ionic liquid as the microwave absorption medium.
AB  - Ionic liquid was used as microwave absorption medium and applied to the
      extraction of essential oils from dried fruits of the Illicium verum Hook. f. and
      Cuminum cyminum L. by microwave-assisted extraction. The extraction time is less
      than 15 min at the microwave power of 440 W. The constituents of essential oils
      obtained by the proposed method were compared with those obtained by
      hydrodistillation. There is no obvious difference in the constituents of
      essential oils obtained by the two methods.

PMID- 19764053
TI  - Trace analysis of glyclazide in human plasma at microscale level by mass
      spectrometry.
AB  - Green (reagents and organic solvents saving) analytical chemistry is a new
      strategy for pharmaceutical analysis. The principles of this idea include primary
      elimination or at least reduction of the amounts of organic reagents and
      solvents. In this study, we have provided two simple methods for the analysis of
      clinical drugs in human plasma. One is the capillary LC (Cap LC) connected to MS
      MS, the other is the matrix-assisted laser desorption ionization (MALDI)
      connected to TOF MS. Sulfonylurea drugs are usually used in diabetes mellitus
      patients. Diabetes is a syndrome of disordered metabolism resulting in abnormally
      high blood sugar levels (hyperglycemia). These microscale methods were
      successfully applied for the monitoring of drug levels in human plasma using
      gliclazide (a second-generation sulfonylurea) as the test platform. The
      sensitivity of these methods is sufficient for detecting the gliclazide within a
      therapeutic range. All the analytical procedures (including human plasma, sample
      preparation, and flow rate of the analytical system) were at microscale level.
      These two methods would lower the consumption of organic solvents further
      safeguarding our environment.

PMID- 19764054
TI  - Ionic liquid-based ultrasound-assisted extraction of fangchinoline and
      tetrandrine from Stephaniae tetrandrae.
AB  - An ionic liquid-based ultrasound-assisted extraction method has been developed
      for the effective extraction of fangchinoline and tetrandrine from Stephaniae
      tetrandrae. The effects of some ultrasound-assisted extraction parameters
      including the concentration of [BMIM][BF(4)], pH, ultrasonic power and time were
      investigated to optimize the ultrasound-assisted extraction conditions. Compared
      to the regular ultrasound-assisted extraction and traditional refluent
      extraction, the proposed [BMIM][BF(4)]-based ultrasound-assisted extraction
      offered shorter extraction times (from 6 h to 40 min) and remarkable higher
      efficiencies (approximately 30% improved), which supported the suitability of the
      proposed approach. In addition, the proposed approach was confirmed by the good
      correlation coefficient (R(2)), recovery and reproducibility (RSD, n = 5), which
      were in the range of 0.9992-0.9995, 85.5-101.1%, and 1.87-4.33%, respectively.

PMID- 19764055
TI  - Sieve-based device for MALDI sample preparation. II. Instrumental
      parameterization.
AB  - A simple device effective for matrix-assisted laser desorption/ionization (MALDI)
      sample preparation, based on the spraying of matrix/sample solution through a
      stainless steel sieve (sieve-based device, SBD), has been employed for the
      preparation of MALDI samples of peptides, polysaccharides and high molecular
      weight proteins. The instrumental parameters, mainly the sprayer voltage,
      solution and auxiliary gas flows, and distances between sprayer-sieve and sieve
      MALDI sample holder have been optimized. The MALDI spectra obtained by laser
      irradiation of the microspots so obtained, exhibit resolution and sensitivity
      higher than those achieved by the commonly employed dried droplets (DD) method.
      Worth noting is the fact that, in contrast to what is observed in the DD method,
      identical spectra are obtained by irradiation of different areas of the MALDI
      sample, showing that by using the SBD the matrix/analyte ratio is constant over
      the entire surface.

PMID- 19764056
TI  - Development of a higher power intermediate-frequency magnetic field exposure
      system for in vitro studies.
AB  - In a previous article we developed an in vitro 23 kHz magnetic field (MF)
      exposure system that generated an MF of 532 microT(rms). Using this system, the
      biological effects of 23 kHz MFs on cell functions have been reported. To further
      clarify the biological effect of intermediate-frequency (IF) MFs and investigate
      the dose-response relationship in cell lines, an exposure system that generates
      stronger MFs is required. To meet this requirement, we developed a 6.25 mT(rms)
      MF exposure system for in vitro study. This level is 1000 times the reference
      level for the general public in the ICNIRP guidelines. This system provides an MF
      of 6.25 mT(rms) at 23 kHz with a uniformity within +/-5%. To verify that in vitro
      experimental conditions are maintained, we examined the temperature,
      environmental MF, and MF leakage for a sham exposure system. In addition, we
      examined the harmonics, coil shape, and heat generated in the medium by the high
      strength MF. As a result, it was confirmed that this system can be used to
      evaluate the biological effects of IF MFs. This article presents the design and
      successful construction of the in vitro exposure system.

PMID- 19764057
TI  - Evidence of field-evolved resistance to Cry1Ac-expressing Bt cotton in
      Helicoverpa armigera (Lepidoptera: Noctuidae) in northern China.
AB  - BACKGROUND: Evolution of resistance threatens the continued success of transgenic
      crops expressing insecticidal proteins. One of the key factors for successful
      resistance management is the timely implementation of monitoring programmes to
      detect early changes of resistance allele frequency in field populations.
      F(1)/F(2) screen, dose-response bioassays and field survey were used to monitor
      resistance to the Cry1Ac-expressing cotton in a field population of Helicoverpa
      armigera (Hubner), the primary target of transgenic Bt cotton in China. RESULTS:
      Field survey showed an increased trend of egg populations of H. armigera on Bt
      cotton in the Qiuxian area from 2003 to 2007. By using the F(2) screening
      procedure, the resistance allele frequency in the Qiuxian (Hebei, China)
      population of H. armigera collected during 2007 was estimated to be 0.075 (95%
      CI: 0.053-0.100), which was 12 times greater than that estimated 9 years ago.
      Dose-response bioassay with the field population collected from the same area
      showed a significant resistance level (11-fold) to Cry1Ac toxin compared to a
      laboratory susceptible strain. CONCLUSION: This study documented a case of field
      evolved resistance in H. armigera after several years of intensive planting of Bt
      cotton. Proactive tactics must be adopted to prevent further increase of
      resistance gene frequency in the Qiuxian region.

PMID- 19764060
TI  - Miniaturization in Asia Pacific 2009.

PMID- 19764061
TI  - Recursion approach for moving neutralization boundary formed on IPG strips. Part
      I: With strong alkali rehydration buffer.
AB  - Moving neutralization boundary (MNB) is an important foundation to understand and
      improve IEF. However, there are obstacles in theoretical predictions of MNB on
      IPG strips due to the unknown local concentrations of carrier ampholytes on
      commercial IPG strips and the time-varying boundary velocities. We introduce a
      recursion approach to extend the current MNB theories into the space-time varying
      MNB system. The recursion approach emphasizes the localizability of
      physicochemical parameters in the discrete time intervals and local positions in
      Lagrangian coordinates, such as local concentrations of carrier ampholytes, local
      OH concentrations, local boundary velocities, local judgments, etc. The boundary
      position recursion equation in a complete time sequence was presented to
      quantitatively predict the MNB position-time curves by distinguishing three kinds
      of titration cases according to NaOH concentrations in rehydration buffers. The
      theoretical position-time curves and local relative judgments of boundaries were
      satisfactorily validated by corresponding images of boundary migrations achieved
      from the IPG-MNB experiments with the some typical NaOH concentrations
      bromophenol blue-rehydration buffers on pH 4-7 IPG strips. The results achieved
      herein have evident significances to the development of moving reaction boundary
      and IEF.

PMID- 19764062
TI  - Continuous particle separation based on electrical properties using alternating
      current dielectrophoresis.
AB  - A design of a microchannel for continuous separation of particles based on
      alternating current dielectrophoretic is studied. The geometric design parameters
      are determined by analyzing the dielectrophoresis force field inside the
      microchannel corresponding to the most efficient separation. The trajectories of
      5 and 10 microm spherical particles are derived analytically using Lagrangian
      tracking method to examine the feasibility and the effectiveness of the design.
      The effects of the mean flow velocity inside the channel and the applied voltage
      across the channel on the performance of the separation are also discussed.

PMID- 19764063
TI  - Enhancement of electrokinetically driven microfluidic T-mixer using frequency
      modulated electric field and channel geometry effects.
AB  - This study reports improved electrokinetically driven microfluidic T-mixers to
      enhance their mixing efficiency. Enhancement of electrokinetic microfluidic T
      mixers is achieved using (i) an active approach of utilizing a pulsating EOF, and
      (ii) a passive approach of using the channel geometry effect with patterned
      blocks. PDMS-based electrokinetic T-mixers of different designs were fabricated.
      Experimental measurements were carried out using Rhodamine B to examine the
      mixing performance and the micro-particle image velocimetry technique to
      characterize the electrokinetic flow velocity field. Scaling analysis provides an
      effective frequency range of applied AC electric field. Results show that for a T
      mixer of 10 mm mixing length, utilizing frequency modulated electric field and
      channel geometry effects can increase the mixing efficiency from 50 to 90%. In
      addition, numerical simulations were performed to analyze the mixing process in
      the electrokinetic T-mixers with various designs. The simulation results were
      compared with the experimental data, and reasonable agreement was found.

PMID- 19764064
TI  - A proteomic and transcriptomic view of amino acids catabolism in the yeast
      Yarrowia lipolytica.
AB  - The yeast Yarrowia lipolytica has to develop dynamic metabolic adaptation
      mechanisms to survive within the cheese habitat. The availability of amino acids
      (AAs) is of major importance for microbial development and/or aroma production
      during cheese ripening. Using 2-D protein gel electrophoresis, we analyzed the
      adaptation mechanisms of Y. lipolytica for AAs limitation or supplementation in a
      batch culture containing lactate as a carbon source. Proteome analyses allow the
      identification of 34 differentially expressed proteins between the culture
      conditions. These analyses demonstrated that prior to the AAs addition, mainly
      proteins involved in the oxidative stress of the yeast were induced. Following
      the AAs addition, yeast cells reorganize their metabolism toward AAs catabolism
      and also generate a higher induction of proteins related to carbon metabolism and
      proteins biosynthesis. Using real-time reverse transcription PCR, we re-evaluated
      the expression of genes encoding proteins involved in these processes. The
      expression levels of the genes were in accordance with the proteomic results,
      with the up-regulation of genes encoding a branched-chain amino transferase BAT2,
      a pyruvate decarboxylase PDC6 and an Hsp70 protein SSZ1 involved in protein
      biosynthesis. A volatile compound analysis was also performed, and increased
      production of dimethyldisulfide from methionine and 3-methyl-butanal from leucine
      was observed in media supplemented with AAs.

PMID- 19764065
TI  - The Ussing type chamber model to study the intestinal transport and modulation of
      specific tight-junction genes using a colonic cell line.
AB  - Polyphenols in apples, such as various hydroxycinnamic acids and flavonoids, have
      positive health effects that strongly depend on their bioavailability. In order
      to show that the Ussing-type chamber is a useful model to study metabolism,
      transport, and tightness of cell monolayers in one experimental setup, monolayers
      of the T84 colon carcinoma cell line mounted in Ussing-type chambers were
      incubated in the presence of physiological concentrations of various
      hydroxycinnamic acids (including ferulic, isoferulic, cinnamic, and hydrocinnamic
      acids) and flavonoids for 4 h. Concentrations of each tested polyphenol in the
      apical chamber, basolateral chamber, and those associated with the cells were
      then determined using HPLC with DAD (HPLC-DAD). The transport studies showed that
      the amounts of the tested polyphenols that passed from the apical to the
      basolateral side of the T84 monolayers depended on their polarity. Metabolites,
      such as glucuronides and sulfates of ferulic acid, were also detected at
      measurable levels by HPLC-ESI-MS/MS in the model system, but only when they were
      supplied at supra-physiological concentrations (>100 microM). In addition, the
      transepithelial resistance (TER) of T84 monolayers was measured before and after
      the addition of polyphenols, with and without short-term exposure to apical
      sodium caprate (C10), a tight junction (TJ) modulator. Exposure to C10 induced a
      decrease in TER that was reversible by incubation with polyphenols. However, no
      increase in paracellular permeability of tested polyphenols was observed after
      apical C10 exposure, so C10 did not promote fluxes of hydroxycinnamic acids
      across the monolayers. Further, real-time PCR analysis of the T84 colon cell line
      showed that ferulic and isoferulic acids induced significant increases in
      expression of the TJ components zonula occludens-1 (ZO-1) and claudin-4
      transcription, but reductions in occludin expression. In contrast, caffeic and p
      coumaric acids had no significant effects on the transcription of either ZO-1 or
      occludin. Our results provide confirmation that T84 cells could be used as model
      system to simulate the intestinal mucosa, and that polyphenols are able to
      increase the TER of C10-treated and -untreated T84 monolayers.

PMID- 19764066
TI  - The complex links between dietary phytochemicals and human health deciphered by
      metabolomics.
AB  - A large variety of phytochemicals commonly consumed with the human diet,
      influence health and may contribute to the prevention of diseases. However, it is
      still difficult to make nutritional recommendations for these bioactive
      compounds. Current studies of phytochemicals are generally focused on specific
      compounds and their effects on a limited number of markers. New approaches are
      needed to take into account both the diversity of phytochemicals found in the
      diet and the complexity of their biological effects. Recent progress in high
      throughput analytical technologies and in bioinformatics now allows the
      simultaneous analysis of the hundreds or more metabolites constituting the
      metabolome in urine or plasma. These analyses give complex metabolic fingerprints
      characteristic of a given phenotype. The exploitation of the wealth of
      information it contains, in randomized controlled trials and cohort studies,
      should lead to the discovery of new markers of intake for phytochemicals and new
      markers of effects. In this paper, we briefly review the current methods used to
      evaluate intake of phytochemicals and their effects on health. We then describe
      the applications of metabolomics in this field. Recent metabolomics studies
      illustrate the potential of such a global approach to explore the complex
      relationships linking phytochemical intake and metabolism and health.

PMID- 19764067
TI  - Influence of apple polyphenols on inflammatory gene expression.
AB  - Apples (Malus spp., Rosaceae) and products thereof contain high amounts of
      polyphenols which show diverse biological activities and may contribute to
      beneficial health effects, like protecting the intestine against inflammation
      initiated by chronic inflammatory bowel diseases (IBD). IBD are characterized by
      an excessive release of several proinflammatory cytokines and chemokines by
      different cell types which results consequently in an increased inflammatory
      response. In the present study we investigated the preventive effectiveness of
      polyphenolic juice extracts and single major constituents on inflammatory gene
      expression in immunorelevant human cell lines (DLD-1, T84, MonoMac6, Jurkat)
      induced with specific stimuli. Besides the influence on proinflammatory gene
      expression, the effect on NF-kappaB-, IP-10-, IL-8-promoter-, STAT1-dependent
      signal transduction, and the relative protein levels of multiple released
      cytokines and chemokines were studied. DNA microarray analysis of several genes
      known to be strongly regulated during gastrointestinal inflammation, combined
      with quantitative real-time PCR (qRT-PCR) revealed that the apple juice extract
      AE04 (100-200 microg/mL) significantly inhibited the expression of NF-kappaB
      regulated proinflammatory genes (TNF-alpha, IL-1beta, CXCL9, CXCL10),
      inflammatory relevant enzymes (COX-2, CYP3A4), and transcription factors (STAT1,
      IRF1) in LPS/IFN-gamma stimulated MonoMac6 cells without significant effects on
      the expression of house-keeping genes. A screening of some major compounds of
      AE04 revealed that the flavan-3-ol dimer procyanidin B(2 )is mainly responsible
      for the anti-inflammatory activity of AE04. Furthermore, the dihydrochalcone
      aglycone phloretin and the dimeric flavan-3-ol procyanidin B(1 )significantly
      inhibited proinflammatory gene expression and repressed NF-kappaB-, IP-10-, IL-8
      promoter-, and STAT1-dependent signal transduction in a dose-dependent manner.
      The influence on proinflammatory gene expression by the applied polyphenols
      thereby strongly correlated with the increased protein levels investigated by
      human cytokine array studies. In summary, we evaluated selected compounds
      responsible for the anti-inflammatory activity of AE04. In particular,
      procyanidin B(1), procyanidin B(2), and phloretin revealed anti-inflammatory
      activities in vitro and therefore may serve as transcription-based inhibitors of
      proinflammatory gene expression.

PMID- 19764068
TI  - Dietary fiber, low-molecular-weight food constituents and colo-rectal
      inflammation in animal models -- a review.
AB  - This review provides an overview over studies in experimental animals aimed at
      elucidating the influence of dietary constituents on colo-rectal inflammation.
      Human studies as well as in vitro investigations will not be covered. In
      experimental animals, a variety of chemical treatments and genetic modifications,
      lead to various types of gut inflammation. In a number of these models, there is
      good evidence for an anti-inflammatory action of dietary tocopherols, certain
      polyphenols, and curcumin at relatively high oral doses. It has also been
      established, that oral application of fats and oils rich in n-3 PUFAs and/or
      conjugated linoleic acid (CLA) can attenuate certain types of colitis in
      experimental animal models. While the effect of dietary calcium on experimental
      colitis is less clear, there are hints indicating that certain high-fiber diets
      or diets rich in digestion-resistant carbohydrates ("fiber") can attenuate
      experimental colitis in animals, although contradictory results have been
      reported. In summary, the anti-inflammatory potency of dietary constituents on
      colon inflammation in experimental animals seems to be rather limited. The
      reasons for this lack of activity seem to be manifold including pharmacokinetic
      limitations and intestinal degradation of the compounds, in particular
      insufficient local, i. e., intra- or sub-mucosal levels of the effective
      compounds, and general limitations of animal models.

PMID- 19764069
TI  - The cost-effectiveness of a law banning the use of cellular phones by drivers.
AB  - OBJECTIVE: To assess the cost-effectiveness of a law banning the use of cellular
      phones by drivers in the Canadian province of Alberta. METHOD: Cost-effectiveness
      analysis using a probabilistic decision-analytic model and publicly available
      data. We adopted a societal perspective. Health gains were measured in terms of
      quality-adjusted life-years. Costs include those associated with awareness
      raising, enforcement and the welfare loss associated with the reduction in
      cellular phone use, less savings in health care and other costs associated with
      automobile accidents. RESULTS: A ban promotes health and releases resources worth
      more than the costs. There is an 80% chance that a ban will be 'cost saving', and
      a 94% chance that a ban will cost less than Can$50,000/QALY. The results are
      sensitive to the additional risk posed by cellular phone use while driving, and
      the rate and pattern with which drivers comply with a ban. CONCLUSION: Under our
      base line assumptions a cellular phone ban is likely to be cost saving from a
      societal perspective. The results are sensitive to parameters for which there is
      very little information or for which the available information is contradictory.

PMID- 19764070
TI  - Sequencing analysis of mutations induced by N-ethyl-N-nitrosourea at different
      sampling times in mouse bone marrow.
AB  - In our previous study (Wang et al., 2004, Toxicol. Sci. 82: 124-128), we observed
      that the cII gene mutant frequency (MF) in the bone marrow of Big Blue mice
      showed significant increase as early as day 1, reached the maximum at day 3 and
      then decreased to a plateau by day 15 after a single dose of carcinogen N-ethyl-N
      nitrosourea (ENU) treatment, which is different from the longer mutation
      manifestation time and the constancy of MFs after reaching their maximum in some
      other tissues. To determine the mechanism underlying the quick increase in MF and
      the peak formation in the mutant manifestation, we examined the mutation
      frequencies and spectra of the ENU-induced mutants collected from different
      sampling times in this study. The cII mutants from days 1, 3 and 120 after ENU
      treatment were randomly selected from different animals. The mutation frequencies
      were 33, 217, 305 and 144 x 10(-6) for control, days 1, 3, and 120, respectively.
      The mutation spectra at days 1 and 3 were significantly different from that at
      day 120. Considering that stem cells are responsible for the ultimate MF plateau
      (day 120) and transit cells are accountable for the earlier MF induction (days 1
      or 3) in mouse bone marrow, we conclude that transit cells are much more
      sensitive to mutation induction than stem cells in mouse bone marrow, which
      resulted in the specific mutation manifestation induced by ENU.

PMID- 19764071
TI  - Validation of the Comprehensive ICF Core Set for obstructive pulmonary diseases
      from the perspective of physiotherapists.
AB  - BACKGROUND AND PURPOSE: The 'Comprehensive ICF Core Set for obstructive pulmonary
      diseases' (OPD) is an application of the International Classification of
      Functioning, Disability and Health (ICF) and represents the typical spectrum of
      problems in functioning of patients with OPD. To optimize a multidisciplinary and
      patient-oriented approach in pulmonary rehabilitation, in which physiotherapy
      plays an important role, the ICF offers a standardized language and understanding
      of functioning. For it to be a useful tool for physiotherapists in rehabilitation
      of patients with OPD, the objective of this study was to validate this
      Comprehensive ICF Core Set for OPD from the perspective of physiotherapists.
      METHOD: A three-round survey based on the Delphi technique of physiotherapists
      who are experienced in the treatment of OPD asked about the problems, resources
      and aspects of environment of patients with OPD that physiotherapists treat in
      clinical practice (physiotherapy intervention categories). Responses were linked
      to the ICF and compared with the existing Comprehensive ICF Core Set for OPD.
      RESULTS: Fifty-one physiotherapists from 18 countries named 904 single terms that
      were linked to 124 ICF categories, 9 personal factors and 16 'not classified'
      concepts. The identified ICF categories were mainly third-level categories
      compared with mainly second-level categories of the Comprehensive ICF Core Set
      for OPD. Seventy of the ICF categories, all personal factors and 15 'not
      classified' concepts gained more than 75% agreement among the physiotherapists.
      Of these ICF categories, 55 (78.5%) were covered by the Comprehensive ICF Core
      Set for OPD. CONCLUSION: The validity of the Comprehensive ICF Core Set for OPD
      was largely supported by the physiotherapists. Nevertheless, ICF categories that
      were not covered, personal factors and not classified terms offer opportunities
      towards the final ICF Core Set for OPD and further research to strengthen
      physiotherapists' perspective in pulmonary rehabilitation.

PMID- 19764072
TI  - Occupational cancer in Italy: evaluating the extent of compensated cases in the
      period 1994-2006.
AB  - OBJECTIVE: The aim of this study is to analyze occupational cancer claims
      compensated in the industrial sector in Italy between 1994 and 2006. METHODS: A
      descriptive analysis of compensated occupational cancers based on the Italian
      Workers' Compensation Authority (INAIL) data was performed. Summary statistics
      were compiled by sex and age of worker, cancer type, workplace agent and economic
      sector. The temporal trend in the period 1994-2006 was investigated for the most
      frequently compensated cancers (mesothelioma and lung cancer from asbestos; nasal
      cavities cancer from wood and leather dust). RESULTS: Between 1994 and 2006,
      6,243 cancer claims were compensated by INAIL due to occupational exposure in the
      industrial sector. Most (5,288, or 85%) of these compensated claims occurred in
      the period 2000-2006, when the annual mean of the most compensated cancers
      increased approximately four times compared to the period 1994-1999. CONCLUSIONS:
      There is an increasing trend in compensation for work-related cancers in Italy in
      recent years, even if occupational cancers are still widely underreported.

PMID- 19764073
TI  - Development of a new electron ionization/field ionization ion source for gas
      chromatography/time-of-flight mass spectrometry.
AB  - We have developed a combined EI/FI source for gas chromatography/orthogonal
      acceleration time-of-flight mass spectrometry (GC/oaTOFMS). In general, EI
      (electron ionization) and FI (field ionization) mass spectra are complementary:
      the EI mass spectrum contains information about fragment ions, while the FI mass
      spectrum contains information about molecular ions. Thus, the comparative study
      of EI and FI mass spectra is useful for GC/MS analyses. Unlike the conventional
      ion sources for FI and EI measurements, the newly developed source can be used
      for both measurements without breaking the ion source vacuum or changing the ion
      source. Therefore, the combined EI/FI source is more preferable than the
      conventional EI or FI ion source from the viewpoint of the reliability of
      measurements and facility of operation. Using the combined EI/FI source, the
      complementarity between EI and FI mass spectra is demonstrated experimentally
      with n-hexadecane (100 pg): characteristic fragment ions for the n-alkane such as
      m/z 43, 57, 71, and 85 are obtained in the EI mass spectrum, while only the
      parent peak of m/z 226 (M+) without any fragment ions is observed in the FI mass
      spectrum. Moreover, the field desorption (FD) measurement is also demonstrated
      with poly(ethylene glycol)s M600 (10 ng) and M1000 (15 ng). Signals of [M+H]+,
      [M+Na]+ and [M+K]+ are clearly detected in the FD mass spectra.

PMID- 19764074
TI  - Electron-induced dissociation of doubly protonated betaine clusters: controlling
      fragmentation chemistry through electron energy.
AB  - The [M21+2H]2+ cluster of the zwitterion betaine, M = (CH3)3NCH2CO2, formed via
      electrospray ionisation (ESI), has been allowed to interact with electrons with
      energies ranging from >0 to 50 eV in a Fourier transform ion cyclotron resonance
      (FT-ICR) mass spectrometer. The types of gas-phase electron-induced dissociation
      (EID) reactions observed are dependent on the energy of the electrons. In the low
      energy region up to 10 eV, electrons are mainly captured, forming the charge
      reduced species, {[M21+2H]+*}*, in an excited state, which stabilises via the
      ejection of an H atom and one or more neutral betaines. In the higher energy
      region, above 12 eV, a Coulomb explosion of the multiply charged clusters is
      observed in highly asymmetric fission with singly charged fragments carrying away
      more than 70% of the parent mass. Neutral betaine evaporation is also observed in
      this energy region. In addition, a series of singly charged fragments appears
      which arise from C-X bond cleavage reactions, including decarboxylation and CH3
      group transfer. These latter reactions may arise from access of electronic
      excited states of the precursor ions.

PMID- 19764076
TI  - Polymicrogyria in fetal alcohol syndrome.
AB  - BACKGROUND: Intrauterine exposure to alcohol may result in a distinct pattern of
      craniofacial abnormalities and central nervous system dysfunction, designated
      fetal alcohol syndrome (FAS). The spectrum of malformations of the brain
      associated with maternal alcohol abuse during pregnancy is much broader than the
      relatively uniform clinical phenotype of FAS. Among these malformations the most
      striking abnormalities involve the impairment of neuronal cell migration.
      However, polymicrogyria (PMG) has so far been reported only once in a human
      autopsy study of a child with FAS. CASE: A 16-year-old girl with confirmed
      maternal alcohol consumption during pregnancy and full phenotype of FAS presented
      after two generalized epileptic seizures for neurologic assessment. Cranial
      magnetic resonance imaging revealed bilateral PMG in the superior frontal gyrus
      with asymmetric distribution. History, clinical features, and genetic
      investigations provided no evidence for any of the known genetic or acquired
      causes of PMG. Therefore, we propose that prenatal alcohol exposure is the cause
      of PMG in this patient rather than a mere coincidence. CONCLUSION: Our
      observation represents only the second patient of PMG in FAS and confirms the
      phenotypic variability of cerebral malformations associated with maternal alcohol
      abuse during pregnancy. In patients with clinical features of FAS and neurologic
      deficits or seizures neuroimaging is recommended. Furthermore, FAS should be
      considered as a differential diagnosis for PMG.

PMID- 19764075
TI  - Association of congenital cardiovascular malformations with 33 single nucleotide
      polymorphisms of selected cardiovascular disease-related genes.
AB  - INTRODUCTION: Clark (1996) proposed that abnormal blood flow is related to some
      congenital cardiovascular malformations (CCVMs), particularly CCVM with
      obstruction to blood flow. Our hypothesis is that CCVMs may relate to genes that
      affect blood coagulation or flow. We studied whether polymorphisms of such genes
      are related to CCVMs; previous association of these SNPs to conotruncal CCVMs is
      described. METHODS: We assessed risk of pulmonary stenosis (PS, N = 120), atrial
      septal defect (ASD, N = 108), aortic stenosis (AS, N = 36), and coarctation of
      the aorta (CoAo, N = 64), associated with 33 candidate genes, selected for their
      relationship to blood flow affected by homocysteine metabolism, coagulation, cell
      cell interaction, inflammation, or blood pressure regulation. RESULTS: Effects
      were specific to cardiac phenotype and race. CoAo was associated with MTHFR (
      667) C>T (odds ratio [OR] for TT 3.5, 95% confidence limits [CI] 1.4-8.6). AS was
      associated with a polymorphism of SERPINE1, G5>G4, OR = 5.6 for the homozygote
      with 95% CI 1.4-22.9. Unique polymorphisms were associated with increased risk of
      ASD and PS: NPPA 664G>A with ASD (OR of 2.4, 95%CI 1.3-4.4) and NOS3 (-690) C>T
      with PS (OR 6.1; 95% CI 1.6-22.6 in the African American population only). For
      ASD, the NPPA (-664) G>A SNP there was increased risk from the variant genotype
      only in maternal smokers (OR 2.6; 95% CI 1.0-7.2). CONCLUSIONS: Genes affecting
      vascular function and coagulation appear to be promising candidates for the
      etiology of cardiac malformations and warrant further study.

PMID- 19764077
TI  - CHM gene molecular analysis and X-chromosome inactivation pattern determination
      in two families with choroideremia.
AB  - Choroideremia is an X-linked recessive retinal dystrophy characterized by
      progressive loss of the photoreceptor, the retinal pigment epithelium, and the
      choriocapillaris layers which ultimately can result in blindness by the fifth
      decade of life. The disease is caused by mutations in the gene CHM, which encodes
      a protein involved in the regulation of intracellular vesicular traffic.
      Typically, hemizygous males are affected by the disease and female carriers are
      asymptomatic with only a diffuse mottled pattern of hyperpigmentation on
      funduscopy. Uncommon instances of fully affected females have been described
      previously and these cases are proposed to arise from an skewed Lyonization
      mechanism preferentially inactivating the X chromosome carrying the normal CHM
      allele. In this work, the clinical and molecular features of two Mexican families
      with choroideremia are described. A novel and a previously described CHM mutation
      were identified. X-chromosome inactivation assays were performed in a total of 12
      heterozygous carriers from the two families. In an affected female from family A,
      a random X-inactivation pattern was demonstrated; on the other hand, in a female
      carrier from family B displaying a conspicuous pattern of pigment epithelium
      mottling at the peripheral retina, a skewed X-inactivation pattern was found.
      However, the X-chromosome preferentially inactivated in this female was the one
      carrying the mutated allele. Our results add to the genotypic spectrum in
      choroideremia and does not support a correlation between X-inactivation status
      and abnormal retinal phenotype in heterozygous female carriers from these two
      families.

PMID- 19764078
TI  - Cytometric rulers with nanometer scaling.

PMID- 19764082
TI  - Use of an audience response system during peer teaching among physical therapy
      students in human gross anatomy: perceptions of peer teachers and students.
AB  - An audience response system (ARS) has become popular among educators in medicine
      and the health professions because of the system's ability to engage listeners
      during a lecture presentation. No one has described the usefulness of ARS
      technology during planned nonlecture peer teaching sessions in gross anatomy
      instruction for health professionals. The unique feature of each peer teaching
      session was a nongraded 12-15 item ARS quiz assembled by six second-year doctor
      of physical therapy (DPT) students and purposely placed at the beginning of the
      review session for those first-year DPT students in attendance. This study used a
      ten-item questionnaire and a five-point Likert scale in addition to three open
      ended questions to survey perceptions of both first-year and second-year DPT
      students about the usefulness of ARS technology implemented during weekly
      interactive peer teaching sessions during a semester course in Anatomy for
      Physical Therapists. First-year students overwhelmingly acknowledged the ARS
      system permitted each student to self-assess his/her preparedness for a quiz or
      examination and compare his/her performance with that of classmates. Peer
      teachers recognized an ARS quiz provided them an opportunity to: (1) estimate
      first-year students' level of understanding of anatomical concepts; and (2)
      effectively prepare first-year students for their weekly quizzes and future
      examinations. On the basis of the mutual benefits derived by both students/tutees
      and teachers/tutors, physical therapist educators may wish to consider using ARS
      technology to enhance teaching methods for a class in gross human anatomy.

PMID- 19764083
TI  - Surgical clinical correlates in anatomy: design and implementation of a first
      year medical school program.
AB  - Medical students state the need for a clinically oriented anatomy class so to
      maximize their learning experience. We hypothesize that the first-year medical
      students, who take the Surgical Clinical Correlates in Anatomy program, will
      perform better than their peers in their anatomy course, their surgical
      clerkships and ultimately choose surgical residencies. We designed and recently
      implemented this program for first-year medical students. It consisted of General
      Surgical Knowledge, Orthopedic Surgery, Plastic Surgery, Urology, Cardiothoracic
      Surgery, General Surgery, Vascular Surgery, and Ear, Nose, and Throat (ENT)
      sessions. Each session had defined learning objectives and interactive cadaveric
      operations performed by faculty members and students. The program was elective
      and had 25 participants randomly chosen. An evaluative questionnaire was
      completed before and after the program. Comparative analysis of the
      questionnaires, first-year anatomy examination results, clinical surgical
      rotation scores, and residency match results will be completed. The positive
      opinions of surgeons increased for all medical students from the pre-evaluation
      to the post-evaluation, and there was a greater increase in positive opinions for
      our participants. Our participants also had the highest average overall for all
      combined anatomy examinations. A need exists among medical students to develop a
      clinically correlated anatomy program that will maximize their learning
      experience, improve their performance and allow them to make moreinformed career
      choices. The recent implementation of this Surgical Clinical Correlates in
      Anatomy program fulfills this need.

PMID- 19764084
TI  - 5-ASA in ulcerative colitis: improving treatment compliance.
AB  - 5-Aminosalicylic acid (5-ASA) compounds are a highly effective treatment for
      ulcerative colitis (UC). While UC patient compliance in clinical studies is over
      90%, only 40% of patients in every day life take their prescribed therapy.
      Adherence to medication has been emphasized recently by a Cochrane meta-analysis
      that has suggested that future trials of 5-ASA in UC should look at patient
      compliance rather than drug efficacy. Better compliance can be obtained by
      reducing the number of tablets and times of administration. Given that the 5-ASA
      formulations have different delivery systems that split the active moiety in
      various regions of the intestine, it is particularly important that an adequate
      dose of the drug arrives at the inflamed part of the colon. 5-ASA Multi matrix
      (MMx) is a novel, high strength (1.2 g), oral formulation designed for once-daily
      dosing. It releases the active moiety throughout the colon. Different studies
      with this compound have shown that it is as effective as 5-ASA enema in the
      treatment of mild-to-moderate, left-sided UC, and is comparable to a pH
      dependent, delayed release 5-ASA (Asacol), even if given once daily. Recently,
      the effectiveness in the acute phase of UC has been confirmed also in
      maintenance. In conclusion, at present, 5-ASA MMx seems theoretically the best
      agent for maintaining patient compliance, and consequently, treatment
      effectiveness.

PMID- 19764085
TI  - Molecular mechanisms of insulin resistance in chronic hepatitis C.
AB  - It is now widely recognized that chronic hepatitis C (CHC) is associated with
      insulin resistance (IR) and type 2 diabetes, so can be considered a metabolic
      disease. IR is most strongly associated with hepatitis C virus (HCV) genotype 1,
      in contrast to hepatic steatosis, which is associated with genotype 3 infection.
      Apart from the well-described complications of diabetes, IR in CHC predicts
      faster progression to fibrosis and cirrhosis that may culminate in liver failure
      and hepatocellular carcinoma. More recently, it has been recognized that IR in
      CHC predicts a poor response to antiviral therapy. The molecular mechanisms for
      the association between IR and HCV infection are not well defined. This review
      will elaborate on the clinical associations between CHC and IR and summarize
      current knowledge regarding the molecular mechanisms that potentially mediate HCV
      associated IR.

PMID- 19764086
TI  - Treatment of malignant gastric outlet obstruction with endoscopically placed self
      expandable metal stents.
AB  - Malignant gastroduodenal obstruction can occur in up to 20% of patients with
      primary pancreatic, gastric or duodenal carcinomas. Presenting symptoms include
      nausea, vomiting, abdominal distention, pain and decreased oral intake which can
      lead to dehydration, malnutrition, and poor quality of life. Endoscopic stent
      placement has become the primary therapeutic modality because it is safe,
      minimally invasive, and a cost-effective option for palliation. Stents can be
      successfully deployed in the majority of patients. Stent placement appears to
      lead to a shorter time to symptomatic improvement, shorter time to resumption of
      an oral diet, and shorter hospital stays as compared with surgical options.
      Recurrence of the obstructive symptoms resulting from stent occlusion, due to
      tumor ingrowth or overgrowth, can be successfully treated with repeat endoscopic
      stent placement in the majority of the cases. Both endoscopic stenting and
      surgical bypass are considered palliative treatments and, to date, no improvement
      in survival with either modality has been demonstrated. A tailored therapeutic
      approach, taking into consideration patient preferences and involving a
      multidisciplinary team including the therapeutic endoscopist, surgeon, medical
      oncologist, radiation therapist, and interventional radiologist, should be
      considered in all cases.

PMID- 19764087
TI  - Paraneoplastic dermatological manifestation of gastrointestinal malignancies.
AB  - Numerous dermatological disorders have been associated with underlining
      malignancies of the gastrointestinal (GI) tract. Such cutaneous manifestations
      might have an important diagnostic value if they are the sole expressions of
      otherwise asymptomatic carcinomas. The recognition of some typical paraneoplastic
      dermatologic disorders can lead to the prompt diagnosis of the underlying
      malignancy, timely administration of therapy, and ultimately, better prognosis.
      In this review we discuss the most common paraneoplastic dermatological syndromes
      from the perspective of the practicing gastroenterologist. We also outline a
      comprehensive practical approach for the evaluation for occult malignancy in
      patients presenting with cutaneous findings potentially associated with GI
      cancers.

PMID- 19764088
TI  - Squamous cell cancer of the rectum.
AB  - Squamous cell carcinoma of the rectum is a rare malignancy. It appears to be
      associated with chronic inflammatory conditions and infections. The clear
      association seen between Human Papilloma Virus and various squamous cancers has
      not been firmly established for the squamous cell cancer of the rectum. The
      presentation is nonspecific and patients tend to present with advanced stage
      disease. Diagnosis relies on endoscopic examination with biopsy of the lesion.
      Distinction from squamous cell cancer of the anus can be difficult, but can be
      facilitated by immunohistochemical staining for cytokeratins. Staging of the
      cancer with endoscopic ultrasound and computed tomography provides essential
      information on prognosis and can guide therapy. At present, surgery remains the
      main therapeutic option; however recent advances have made chemoradiation a
      valuable therapeutic addition. Squamous cell carcinoma of the rectum is a
      distinct entity and it is of crucial importance for the practicing
      Gastroenterologist to be thoroughly familiar with this disease. Compared to
      adenocarcinoma of the rectum and squamous cell cancer of the anal canal, squamous
      cell carcinoma of the rectum has different epidemiology, etiology, pathogenesis,
      and prognosis but, most importantly, requires a different therapeutic approach.
      This review will examine and summarize the available information regarding this
      disease from the perspective of the practicing gastroenterologist.

PMID- 19764089
TI  - Cytokeratin-18 fragments and biomarkers of the metabolic syndrome in nonalcoholic
      steatohepatitis.
AB  - Nonalcoholic fatty liver disease (NAFLD) remains a leading cause of chronic liver
      disease. In the context of NAFLD, the presence of nonalcoholic steatohepatitis
      (NASH) portends an adverse prognosis with greater risk of liver fibrosis and
      cirrhosis. Although liver biopsy is the keystone of patient management in NAFLD,
      it is also increasingly clear that such evaluation has its limitations. The
      availability of biochemical markers of NAFLD and NASH has tremendous potential to
      radically alter management strategies for these conditions, as well as to monitor
      disease activity. Our article provides an overview of biomarker discovery and
      selection in the setting of NAFLD and highlights future directions in the field.

PMID- 19764090
TI  - Molecular mechanism and functional consequences of lansoprazole-mediated heme
      oxygenase-1 induction.
AB  - AIM: To investigate the molecular mechanism and functional consequences of heme
      oxygenase-1 (HO-1) activation by lansoprazole in endothelial cells and
      macrophages. METHODS: Expression of HO-1 mRNA was analyzed by Northern blotting.
      Western blotting was used to determine the HO-1 and ferritin protein levels.
      NADPH-dependent reactive oxygen species (ROS) formation was measured with
      lucigenin-enhanced chemiluminescence. HO-1 promoter activity in mouse
      fibroblasts, stably transfected with a 15-kb HO-1 gene that drives expression of
      the reporter gene luciferase, was assessed using in vivo bioluminescence imaging.
      RESULTS: Lansoprazole increased HO-1 mRNA levels in endothelial cells and HO-1
      protein levels in macrophages. In addition, lansoprazole-induced ferritin protein
      levels in both cell systems. Moreover, induction of the antioxidant proteins HO-1
      and ferritin by lansoprazole was followed by a decrease in NADPH-mediated ROS
      formation. The radical scavenging properties of lansoprazole were diminished in
      the presence of the HO inhibitor, chromium mesoporphyrin IX. Induction of HO-1
      gene expression by lansoprazole was not related to oxidative stress or to the
      activation of the mitogen-activated protein kinase pathway. However, the
      phosphatidylinositol 3-kinase inhibitor LY294002 showed a concentration-dependent
      inhibition of HO-1 mRNA and promoter activity. CONCLUSION: Activation of HO-1 and
      ferritin may account for the gastric protection of lansoprazole and is dependent
      on a pathway blocked by LY294002.

PMID- 19764091
TI  - Identification of the layered morphology of the esophageal wall by optical
      coherence tomography.
AB  - AIM: To assess each layer of the optical coherence tomography (OCT) image of the
      esophageal wall with reference to the histological structure. METHODS: Resected
      specimens of fresh pig esophagus was used as a model for the esophageal wall. We
      injected cyanoacrylate adhesive into the specimens to create a marker, and
      scanned them using a miniature OCT probe. The localization of these markers was
      assessed in the OCT images. Then we compared the OCT-imaged morphology with the
      corresponding histological section, guided by the cyanoacrylate adhesive markers.
      We prepared a second set of experiments using nylon sutures as markers. RESULTS:
      The OCT image of the esophageal specimen has a clear five-layered morphology.
      First, it consisted of a relatively less reflective layer; second, a more
      reflective layer; third, a less reflective layer; fourth, a more reflective
      layer; and fifth, a less reflective layer. Comparing the OCT images with marked
      histological sections showed that the first layer corresponded to stratified
      squamous epithelium; the second to lamina propria; the third to muscularis
      mucosa; fourth, submucosa; and fifth, muscularis propria with deeper structures
      of the esophageal wall. CONCLUSION: We demonstrated that the OCT image of the
      normal esophageal wall showed a five-layered morphology, which corresponds to
      histological esophageal wall components.

PMID- 19764092
TI  - Influence of paeonol on expression of COX-2 and p27 in HT-29 cells.
AB  - AIM: To investigate the effect of paeonol on controlling the proliferation of
      colorectal cancer cell line HT-29 and to discuss its possible mechanism. METHODS:
      The inhibitory effect of paeonol on proliferation of HT-29 cells was detected by
      MTT assay. The results of apoptosis were measured by flow cytometry.
      Immunocytochemical staining was performed to detect the expression of
      cyclooxygenase-2 (COX-2) and protein p27 in HT-29 cells treated with paeonol at
      different concentrations. Reverse transcription-polymerase chain reaction (RT
      PCR) was used for mRNA analysis. RESULTS: From the data of both MTT and flow
      cytometry, we observed that cell proliferation was inhibited by different
      concentrations of paeonol. By immunocytochemical staining, we found that HT-29
      cells treated with paeonol (0.024-1.504 mmol/L) reflected reduced expression of
      COX-2 and increased expression of p27 in a dose-dependent manner. RT-PCR showed
      that paeonol down-regulated COX-2 and up-regulated p27 in a dose- and time
      dependent manner in HT-29 cells. CONCLUSION: One of the apoptotic mechanisms of
      paeonol is down-regulation of COX-2. p27 is up-regulated simultaneously and plays
      an important part in controlling cell proliferation and is a crucial factor in
      the Fas/FasL apoptosis pathway.

PMID- 19764093
TI  - Capecitabine treatment patterns in patients with gastroesophageal cancer in the
      United States.
AB  - AIM: To assess the use of capecitabine-based therapy and associated complication
      rates in patients with gastroesophageal cancer (GEC) in a real-world treatment
      setting. METHODS: Patients with claims between 2004 and 2005 were identified from
      the Thomson Reuters MarketScan databases. Capecitabine regimens were compared
      with 5-fluorouracil (5-FU) and other chemotherapy regimens, and were stratified
      by treatment setting. RESULTS: We identified 1013 patients with GEC:
      approximately half had treatment initiated with a 5-FU regimen, whereas 11% had
      therapy initiated with a capecitabine regimen. The mean capecitabine dose overall
      was 2382 +/- 1118 mg/d, and capecitabine was used as monotherapy more often than
      in combination. Overall, 5-FU regimens were the most common treatment option in
      neoadjuvant and adjuvant settings, while other non-capecitabine regimens were
      used more widely in first- and second-line settings. The overall unadjusted
      complication rate for capecitabine regimens was about half of that seen with 5-FU
      regimens. In multivariate analyses, capecitabine recipients had a 51% (95% CI:
      26%-81%) lower risk of developing any complication than 5-FU recipients did. The
      risk of developing bone marrow, constitutional, gastrointestinal tract,
      infectious, or skin complications was lower with capecitabine therapy than with 5
      FU. CONCLUSION: Capecitabine appeared to have a favorable side effect profile
      compared with 5-FU, which indicates that it may be a treatment option for GEC.

PMID- 19764094
TI  - A Brazilian experience of the self transglutaminase-based test for celiac disease
      case finding and diet monitoring.
AB  - AIM: To evaluate the effectiveness of a rapid and easy fingertip whole blood
      point-of-care test for celiac disease (CD) case finding and diet monitoring.
      METHODS: Three hundred individuals, 206 females (68.7%) and 94 males (31.3%),
      were submitted to a rapid and easy immunoglobulin-A-class fingertip whole blood
      point-of-care test in the doctor's office in order to make immediate clinical
      decisions: 13 healthy controls, 6 with CD suspicion, 46 treated celiacs, 84
      relatives of the celiac patients, 69 patients with dyspepsia, 64 with irritable
      bowel syndrome (IBS), 8 with Crohn's disease and 9 with other causes of diarrhea.
      RESULTS: Upper gastrointestinal endoscopy with duodenal biopsies was performed in
      patients with CD suspicion and in individuals with positive test outcome: in
      83.3% (5/6) of the patients with CD suspicion, in 100% of the patients that
      admitted gluten-free diet transgressions (6/6), in 3.8% of first-degree relatives
      (3/79) and in 2.9% of patients with dyspepsia (2/69). In all these individuals
      duodenal biopsies confirmed CD (Marsh's histological classification). The studied
      test showed good correlation with serologic antibodies, endoscopic and
      histological findings. CONCLUSION: The point-of-care test was as reliable as
      conventional serological tests in detecting CD cases and in CD diet monitoring.

PMID- 19764095
TI  - Sustained virological response in a predominantly hepatitis C virus genotype 4
      infected population.
AB  - AIM: To assess sustained virological response (SVR) rates in a predominantly
      hepatitis C virus (HCV) genotype 4 infected population. METHODS: Between 2003
      2007, 240 patients who were treated for chronic hepatitis C infection at our
      center were included. Epidemiological data, viral genotypes, and treatment
      outcomes were evaluated in all treated patients. Patients with chronic renal
      failure, previous non-responders, and those who relapsed after previous treatment
      were excluded from the study. Among all patients, 57% were treated with PEG
      interferon (IFN) alpha-2a and 43% patients were treated with PEG-IFN alpha-2b;
      both groups received a standard dose of ribavirin. RESULTS: 89.6% of patients
      completed the treatment with an overall SVR rate of 58%. The SVR rate was 54% in
      genotype 1, 44% in genotype 2, 73% in genotype 3, and 59% in genotype 4 patients.
      There was no statistical difference in the SVR rate between patients treated with
      PEG-IFN alpha-2a and PEG-IFN alpha-2b (61.5% vs 53%). Patients younger than 40
      years had higher SVR rates than older patients (75% vs 51%, P = 0.001). SVR was
      also statistically significantly higher when the HCV RNA load (pretreatment) was
      below 800.000 (64% vs 50%, P = 0.023), in patients with a body mass index (BMI)
      less than 28 (65% vs 49%, P = 0.01), and in patients who completed the treatment
      duration (64% vs 8%, P <or= 0.00001). CONCLUSION: The SVR rate in our study is
      higher than in previous studies. Compliance with the standard duration of
      treatment, higher ribavirin dose, younger age, lower BMI, and low pretreatment
      RNA levels were associated with a higher virological response.

PMID- 19764096
TI  - Paraaortic lymph node metastasis in patients with intra-abdominal malignancies:
      CT vs PET.
AB  - AIM: To compare the diagnostic accuracy of computed tomography (CT) and positron
      emission tomography (PET) for the preoperative detection of paraaortic lymph node
      (PAN) metastasis in patients with intra-abdominal malignancies. METHODS: Sixty
      six patients with intra-abdominal malignancies who underwent both CT and PET
      before lymphadenectomy were included in this study. Histopathologically, 13
      patients had metastatic PAN, while 53 had non-metastatic PAN. The CT criteria for
      metastasis were: short diameter of > 8 mm, lobular or irregular shape, and/or
      combined ancillary findings, including necrosis, conglomeration, vessel
      encasement, and infiltration. The PET criterion was positive fluorodeoxyglucose
      (FDG) uptake. The sensitivity, specificity, positive predictive value (PPV),
      negative predictive value (NPV), and accuracy of both modalities were compared
      with the pathologic findings, and the false positive and false negative cases
      with both CT and PET were analyzed. RESULTS: The sensitivity, specificity, PPV,
      NPV, and accuracy of CT were 61.5%, 84.9%, 50%, 90% and 80.3%, respectively. For
      PET, the percentages were 46.2%, 100%, 100%, 88.3%, and 89.4%. Additionally,
      there were 8 false positive CT cases (8/53, 15.1%) and zero false positive PET
      cases. Of the 13 metastatic PANs, there were 5 false negative CT scans (38.5%)
      and 7 (53.9%) false negative PET scans. CONCLUSION: For detecting PAN metastasis,
      CT is more sensitive than PET, while PET is more specific.

PMID- 19764097
TI  - Effects of Chai-Qin-Cheng-Qi Decoction on cefotaxime in rats with acute
      necrotizing pancreatitis.
AB  - AIM: To investigate the effect of Chai-Qin-Cheng-Qi Decoction (CQCQD) on
      cefotaxime (CTX) concentration in pancreas of rats with acute necrotizing
      pancreatitis (ANP). METHODS: Sixty healthy male Sprague-Dawley rats were divided
      randomly into an ANP group (ANP model + CTX, n = 20), treatment group (ANP model
      + CTX + CQCQD, n = 20) and control group (normal rats + CTX, n = 20). ANP models
      were induced by retrograde intraductal injection of 3.5% sodium taurocholate (1
      mL/kg), and the control group was injected intraductally with normal saline. All
      rats were injected introperitoneally with 0.42 g/kg CTX (at 12-h intervals for a
      continuous 72 h) at 6 h after intraductal injection. Meanwhile, the treatment
      group received CQCQD (20 mL/kg) intragastrically at 8-h intervals, and the ANP
      and control group were treated intragastrically with normal saline. At 15 min
      after the last CTX injection, blood and pancreas samples were collected for the
      determination of CTX concentration using validated high-performance liquid
      chromatography. Pathological changes and wet-to-dry-weight (W/D) ratio of
      pancreatic tissue were examined. RESULTS: Serum CTX concentrations in three
      groups were not significantly different. Pancreatic CTX concentration and
      penetration ratio were lower in ANP group vs control group (4.4 +/- 0.6 microg/mL
      vs 18.6 +/- 1.7 microg/mL, P = 0.000; 5% vs 19%, P = 0.000), but significantly
      higher in treatment group vs ANP group (6.4 +/- 1.7 microg/mL vs 4.4 +/- 0.6
      microg/mL, P = 0.020; 7% vs 5%, P = 0.048). The histological scores and W/D ratio
      were significantly decreased in treatment group vs ANP and control group.
      CONCLUSION: CQCQD might have a promotive effect on CTX concentration in
      pancreatic tissues of rats with ANP.

PMID- 19764098
TI  - Preliminary experience of helical tomotherapy for locally advanced pancreatic
      cancer.
AB  - Radiotherapy for locally advanced pancreatic cancer is technically difficult and
      frequently associated with high-grade digestive toxicity. Helical tomotherapy
      (HT) is a new irradiation modality that combines megavoltage computed tomography
      imaging for patient positioning with intensity-modulated fan-beam radiotherapy.
      Its recent availability opens new fields of exploration for pancreatic
      radiotherapy as a result of its ability to tailor very well-defined dose
      distributions around the target volumes. Here, we report the use of HT in two
      patients with locally advanced pancreatic cancer. Doses to the bowel, kidneys and
      liver were reduced significantly, which allowed for excellent treatment tolerance
      without any high-grade adverse effects in either patient.

PMID- 19764099
TI  - Free perforation of the small intestine in collagenous sprue.
AB  - A 67-year-old man with celiac disease developed recurrent diarrhea, profound
      weakness and weight loss, with evidence of marked protein depletion. His clinical
      course was refractory to a strict gluten-free diet and steroid therapy.
      Postmortem studies led to definition of unrecognized collagenous sprue that
      caused ulceration and small intestinal perforation. Although PCR showed identical
      monoclonal T-cell populations in antemortem duodenal biopsies and postmortem
      jejunum, careful pathological evaluation demonstrated no frank lymphoma. Rarely,
      overt or even cryptic T-cell lymphoma may complicate collagenous sprue, however,
      small intestinal ulcers and perforation may also develop independently. The
      dramatic findings here may reflect an underlying or early molecular event in the
      eventual clinical appearance of overt T-cell lymphoma.

PMID- 19764100
TI  - Stevens-Johnson syndrome complicating adalimumab therapy in Crohn's disease.
AB  - The anti-tumor necrosis factor (TNF)alpha medications demonstrate efficacy in the
      induction of remission and its maintenance in numerous chronic inflammatory
      conditions. With the increasing number of patients receiving anti-TNFalpha
      agents, however, less common adverse reactions will occur. Cutaneous eruptions
      complicating treatment with an anti-TNFalpha agent are not uncommon, occurring in
      around 20% of patients. Adalimumab, a fully humanized antibody against TNFalpha,
      may be expected to cause minimal immune-mediated skin reactions compared to the
      chimeric monoclonal antibody, infliximab. We, however, report a case of Stevens
      Johnson syndrome that required hospitalization and cessation of adalimumab in a
      patient with Crohn's disease (CD). In this case report, a 29-year-old male with
      colonic and perianal CD with associated erythema nodosum and large joint
      arthropathy developed severe mucositis, peripheral rash and desquamation, fevers
      and respiratory symptoms concomitant with a second dose of 40 mg adalimumab after
      a 2 mo break from adalimumab therapy. Skin biopsies of the abdominal wall
      confirmed erythema multiforme and the patient was on no other drugs and infective
      etiologies were excluded. The patient responded rapidly to IV hydrocortisone and
      was able to be commenced on infliximab without recurrence of the Stevens-Johnson
      syndrome. Desquamating skin reactions have now been described in three of the
      TNFalpha antagonists (infliximab, etanercept and adalimumab). These reactions can
      be serious and prescribers need to be aware of the potential mucocutaneous side
      effects of these agents, especially as Stevens-Johnson syndrome is associated
      with significant morbidity and mortality.

PMID- 19764101
TI  - Hairy cell leukemia presenting as multiple discrete hepatic lesions.
AB  - The involvement of hairy cell leukemia in the liver is in the form of portal and
      sinusoidal cellular infiltration. Here we describe the first case of hepatic
      hairy cell leukemia presenting as multiple discrete lesions, which was treated
      successfully. We suggest that in the investigation of discrete hepatic lesions in
      cases of cancer of unknown primary, hairy cell leukemia should be considered. The
      excellent response of hairy cell leukemia to therapy highlights the need for such
      a consideration.

PMID- 19764102
TI  - Muscle hematoma: a critically important complication of alcoholic liver
      cirrhosis.
AB  - An iliopsoas hematoma can occur either spontaneously or secondary to trauma or
      bleeding tendency due to hemophilia and anticoagulant therapy. Although liver
      cirrhosis is commonly associated with coagulopathy, iliopsoas hematoma is very
      rare. We herein, present a case of bilateral iliopsoas hematoma in a patient with
      alcoholic cirrhosis, and review the literature on muscle hematoma associated with
      cirrhosis. A 56-year-old man with alcoholic cirrhosis was admitted in a state of
      shock with anemia. The cause of anemia could not be detected, and the patient was
      treated conservatively. The site of bleeding was not detected with either
      gastroduodenal endoscopy or upper abdominal computed tomography, the latter of
      which did not include the iliopsoas muscle. He died on the 10th day of admission
      and bilateral iliopsoas hematomas were found on autopsy. An iron stain was
      positive in the iliopsoas muscle. Eight cases of muscle hematoma associated with
      cirrhosis, including the present case, were found in a review of the literature.
      Four of these cases involved the rectus abdominis muscle, 3 involved the
      iliopsoas muscle and 1 involved combined muscles. Alcoholic cirrhosis accounted
      for 75% of the cases. One case (12.5%) was associated with virus-related
      cirrhosis, and another with combined virus- and alcohol-related cirrhosis. The
      mortality rate was 75% despite early diagnosis and low risk scores for cirrhosis.
      Muscle hematoma in patients with cirrhosis is closely related to alcoholism, and
      the mortality rate of the condition is extremely high. In conclusion, muscle
      hematoma should be recognized as an important complication of cirrhosis.

PMID- 19764103
TI  - Delayed presentation of intrathoracic esophageal perforation after pneumatic
      dilation for achalasia.
AB  - Pneumatic dilation (PD) is considered to be a safe and effective first line
      therapy for achalasia. The major adverse event caused by PD is esophageal
      perforation but an immediate gastrografin test may not always detect a
      perforation. It has been reported that delayed management of perforation for more
      than 24 h is associated with high mortality. Surgery is the treatment of choice
      within 24 h, but the management of delayed perforation remains controversial.
      Hereby, we report a delayed presentation of intrathoracic esophageal perforation
      following PD in a 48-year-old woman who suffered from achalasia. She completely
      recovered after intensive medical care. A review of the literature is also
      discussed.

PMID- 19764104
TI  - Sorafenib induced tumor lysis syndrome in an advanced hepatocellular carcinoma
      patient.
AB  - A 55-year-old male patient with hepatitis B-related liver cirrhosis was found to
      have advanced hepatocellular carcinoma. His AFP was initially 9828 microg/L and
      rapidly dropped to 5597 microg/L in ten days after oral sorafenib treatment.
      However, he developed acute renal failure, hyperkalemia, and hyperuricemia 30 d
      after receiving the sorafenib treatment. Tumor lysis syndrome was suspected and
      intensive hemodialysis was performed. Despite intensive hemodialysis and other
      supportive therapy, he developed multiple organ failure (liver, renal, and
      respiratory failure) and metabolic acidosis. The patient expired 13 d after
      admission.

PMID- 19764105
TI  - Ectopic pancreaticobiliary drainage accompanied by proximal jejunal adenoma: a
      case report.
AB  - A patient with obstructive jaundice was examined by multidetector row helical
      computed tomography (MDCT) and magnetic resonance imaging (MRI), and his common
      bile duct was observed to be leading into the distal portion of the horizontal
      duodenum with a pancreaticobiliary union outside the duodenal wall. A mass was
      also found in the proximal jejunum. All the above findings were confirmed by
      subsequent surgery, thus contrast-enhanced MDCT and MRI with appropriate image
      post-processing could provide non-invasive and accurate information regarding
      anatomy and lesions of the pancreaticobiliary duct and duodenal union, which may
      improve the feasibility of surgery and reduce postoperative complications.

PMID- 19764106
TI  - Papers featured in the World Journal of Gastroenterology from 2006 to 2007.
AB  - AIM: To analyze papers published in the World Journal of Gastroenterology (WJG)
      from 2006 to 2007. We investigated the highly cited papers for geographic
      distribution of the cited authors, as well as the distribution of the citing
      journals and year of citation. METHODS: Papers published in WJG from 2006 to 2007
      and their citations were retrieved from the Science Citation Index Expanded
      (SCIE). The papers and their citations were analyzed according to bibliometric
      methods, including the number of citations for a given paper, the distribution of
      the highly cited papers, the geographic distribution of the cited authors, and
      the years of citation. RESULTS: Two thousand five hundred and six papers
      published in WJG from 2006 to 2007 were collected through SCIE, and 2335 of these
      were categorized as articles, reviews or proceedings. In 2006 and 2007, the
      average citation rate was 85.08% and 70.48%, respectively, and the average number
      of citations per paper was 4.33 and 2.51. Among the 2506 papers, 1963 were cited
      8788 times by other articles. The mean number of citations per paper was 3.51.
      The papers with over three citations accounted for 54.72% of all those that were
      cited, and the total number of citations accounted for 85.38% of the total of
      8788 citations. Thirteen papers were cited over 30 times and the highest number
      of citations for any one paper was 98. The cited authors came from 70 different
      countries or regions, with China, Japan and the United States being the most
      frequent. The highest average citation rate and number of citations per paper
      were for authors from Canada (96.30%, 6.89), Hungary (92.31%, 5.62), Australia
      (88.46%, 5.46), Germany (87.04%, 5.33), and Spain (87.50%, 5.11). The impact
      factor was 2.081 and the self-citation rate was 9.41% in 2008. The papers
      published in WJG in 2006-2007 were cited by 1597 journals. CONCLUSION: The papers
      in WJG have a high number of citations, and have been cited in numerous journals
      by authors from various countries. The results imply that WJG has an influential
      academic profile in gastroenterology around the world.

PMID- 19764107
TI  - Beneficiary effect of Tinospora cordifolia against high-fructose diet induced
      abnormalities in carbohydrate and lipid metabolism in Wistar rats.
AB  - High intake of dietary fructose has been shown to exert a number of adverse
      metabolic eff ects in humans and experimental animals. The present study was
      designed to investigate the eff ect of the aqueous extract of Tinospora
      cordifolia stem (TCAE) on the adverse eff ects of fructose loading toward
      carbohydrate and lipid metabolism in rats. Adult male Wistar rats of body weight
      around 200 g were divided into four groups, two of which were fed with starch
      diet and the other two with high fructose (66 %) diet. Plant extract of TC (400
      mg/kg/day) was administered orally to each group of the starch fed rats and the
      highfructose fed rats. At the end of 60 days of experimental period, biochemical
      parameters related to carbohydrate and lipid metabolism were assayed.
      Hyperglycemia, hyperinsulinemia, hypertriglyceridemia, insulin resistance, and
      elevated levels of hepatic total lipids, cholesterol, triglycerides, and free
      fatty acids (p < 0.05) observed in fructose-fed rats were completely prevented
      with TCAE treatment. Alterations in the activities of enzymes of glucose
      metabolism (hexokinase, phosphofructokinase, pyruvate kinase, glucose-6
      phosphatase, fructose-1,6-bisphosphatase, and glucose-6-phosphate dehydrogenase)
      and lipid metabolism (fatty acid synthetase, lipoprotein lipase, and malic
      enzyme) as observed in the high fructose-fed rats were prevented with TCAE
      administration. In conclusion, our fi ndings indicate improvement of glucose and
      lipid metabolism in high-fructose fed rats by treatment with Tinospora
      cordifolia, and suggest that the plant can be used as an adjuvant for the
      prevention and/or management of insulin resistance and disorders related to it.

PMID- 19764108
TI  - Factors in serum from type 2 diabetes patients can cause cellular insulin
      resistance.
AB  - This pilot study was aimed to investigate whether there are humoral factors in
      serum from type 2 diabetic subjects that, in addition to glucose, insulin and
      free fatty acids are able to induce or contribute to peripheral insulin
      resistance with respect to glucose transport. Isolated subcutaneous adipocytes
      from 11 type 2 diabetic subjects and 10 nondiabetic controls were incubated for
      24-h in medium supplemented with 25 % serum from a control or a type 2 diabetic
      donor, in the presence of a low (5 mM) or a high (15 mM) glucose concentration,
      respectively. After the incubation period glucose uptake capacity was assessed.
      Serum from type 2 diabetic donors, compared to serum from controls, significantly
      reduced the maximal insulin eff ect to stimulate glucose uptake (approximately 40
      %, p < 0.05) in adipocytes from control subjects, independent of surrounding
      glucose concentrations. Glucose uptake capacity in adipocytes isolated from type
      2 diabetic subjects was similar regardless of culture condition. No significant
      alterations were found in cellular content of key proteins in the insulin
      signaling cascade (insulin receptor substrate-1 and -2, and glucose transporter
      4) that could explain the impaired insulin-stimulated glucose transport in
      control adipocytes incubated with serum from type 2 diabetic donors. The present
      findings indicate the presence of biomolecules in the circulation of type 2
      diabetic subjects, apart from glucose, insulin, and free fatty acids with the
      ability to induce peripheral insulin resistance. This further implies that even
      though normoglycemia is achieved other circulating factors can still negatively
      affect insulin sensitivity in type 2 diabetic patients.

PMID- 19764109
TI  - Invited commentary.

PMID- 19764110
TI  - Invited commentary.

PMID- 19764111
TI  - [Comment on the article: "Intramedullary nail removal in the upper and lower
      limbs. Should we recommend this operation?"]].

PMID- 19764113
TI  - Abstracts of the Annual Meeting of the Swiss Society of Pediatrics, June 18-20,
      2009, St. Gall, Switzerland.

PMID- 19764112
TI  - Abstracts of the Annual Meeting of the Swiss Society of Orthopedy and
      Traumatology, June 24-26, 2009, Geneva, Switzerland.

PMID- 19764114
TI  - Abstracts of the Annual Meeting of the Swiss Society of Rheumatology SGR,
      Symposium Health Professionals in Rheumatology combined with the VIth Conference
      on Sex Hormones, Pregnancy and Rheumatic Diseases, September 10-11, 2009,
      Lausanne, Switzerland.

PMID- 19764115
TI  - Abstracts of the Joint Annual Meeting of the Swiss Respiratory Society, Swiss
      Society of Occupational Medicine, Swiss Pediatric Respiratory Society, and the
      Swiss Society for Thoracic Surgery, April 16-17, 2009, Davos, Switzerland.

PMID- 19764116
TI  - Abstracts of the Reha Swiss Congress 2009. Swiss Working Group for Rehabilitation
      (SAR), Swiss Society for Physical Medicine and Rehabilitation (SGPMR),
      Rehabilitation Societies of the 4 Alp Countries, Health Professionals, NFP 53,
      March 12-13, 2009, Interlaken, Switzerland.

PMID- 19764117
TI  - Green cleaning article author responds.

PMID- 19764118
TI  - The 2009 ASMBS Annual Abstract Supplement to Surgery for Obesity and Related
      Diseases (SOARD).

PMID- 19764119
TI  - Search our soul (SOS): the next paradigm shift.

PMID- 19764120
TI  - Nanobioengineering is a rapidly growing field in biomedical engineering.
      Introduction to the Special Issue.

PMID- 19764121
TI  - Thyroid cancer increase mystifying.  Better methods of detection, but new
      research suggests an unknown factor may be involved.

PMID- 19764122
TI  - What's the difference between X-rays and MRIs?

PMID- 19764123
TI  - Global influenza surveillance network:laboratory surveillance and response to
      pandemic H1N1 2009.

PMID- 19764124
TI  - Global detection of wild and vaccine derived polioviruses, January 2008-June
      2009.

PMID- 19764125
TI  - Monthly report on dracunculiasis cases, January-July 2009.

PMID- 19764126
TI  - Use of RFLPs larger than 100 kbp to map the position and  internal organization
      of the nucleolus organizer region on  chromosome 2 in Arabidopsis thaliana.
AB  - In Arabidopsis thaliana ribosomal RNA genes (rRNA genes or rDNA) are grouped in
      two nucleolus organizer regions(NORs) that together comprise approximately 6% of
      the genome. The map positions of the NORs relative to other genetic markers are
      unknown. It was found that the restriction endonuclease Hindlll cuts once in some
      but not all rRNA genes to yield strain-specific RFLPs of 100-700 kb that could be
      visualized by pulsed-field gel electrophoresis and Southern blotting. The Hindlll
      RFLPs of the A. thaliana strains Columbia and Landsberg segregated among
      recombinant inbred lines derived from a cross between these two strains. Linkage
      analysis placed the NOR bearing the polymorphic Hindlll sites to the top of the
      upper arm of chromosome 2. The name NOR2 is suggested for this locus. Hindlll
      bearing rRNA genes ere interspersed with clusters of Hindlll-less genes
      throughout NOR2. The observed clustering is most consistent with unequal crossing
      over, or nearest-neighbor gene conversion, as the mechanism(s) that spread rRNA
      gene variants throughout an NOR. No meiotic cross-over events yielding a 'hybrid'
      NOR with multiple RFLPs from both parents were observed among the 47 recombinant
      inbred lines examined. However,the appearance of novel Hindlll profiles in
      approximately 40% of the recombinant inbred lines demonstrates that fluctuations
      in the distribution of rRNA gene variants occur frequently and can be readily
      detected on pulsed-field gels.

PMID- 19764127
TI  - Completion of national laboratory inventories for wild poliovirus containment -
      WHO Western Pacific Region, December 2008.

PMID- 19764128
TI  - Onchocerciasis: elimination is feasible.

PMID- 19764129
TI  - Onchocerciasis (river blindness). Report from the eighteenth InterAmerican
      Conference on Onchocerciasis, November 2008.

PMID- 19764130
TI  - Vaccine-derived polioviruses detected worldwide, January 2008-June 2009.

PMID- 19764131
TI  - Letter regarding levosimendan in a rat model of severe verapamil poisoning.

PMID- 19764132
TI  - Chlorine dioxide-induced acute hemolysis.

PMID- 19764133
TI  - [Stop attacks against the physician and health institutions].

PMID- 19764134
TI  - [Traumatic subconjuntival hemorrhage. Presentation and associated injuries].
AB  - BACKGROUND: Subconjunctival hemorrhage is frequent in ocular trauma and is
      traditionally left untreated, awaiting spontaneous resolution unless associated
      with open globe injury. A study was performed to identify characteristics of eyes
      with subconjunctival hemorrhage, rate of coexisting additional injuries, and
      whether visual acuity might allow detection of the latter. MATERIAL AND METHODS:
      Patients evaluated for ocular trauma at our service between 1996 and 2000 with
      subconjunctival hemorrhage were included; eyes without visual acuity record were
      eliminated. Each eye was re-qualified according to standardized classification of
      ocular trauma. Presence of additional ocular injuries in eyes with different
      grade (visual acuity) was recorded. Rate of additional injuries by grade was
      compared with chi-square and odds ratio (OR). RESULTS: A total of 178 eyes of 168
      patients aged 1 to 84 years (average 27.63 years, standard deviation (SD) 17.3)
      were evaluated; grade (visual acuity) was 1 in 107 eyes (60.1%), 2 in 35 (19.7%),
      3 in 22 (12.3%), 4 in 11 (6.2%) and 5 in three (1.7%) eyes. Seventy six eyes had
      additional injuries (42.7%, 95% confidence interval [CI 95%] 35.5-49.9%). A
      higher proportion of additional injuries was found in patients with grade < 1
      (66.2%) than in those with grade 1 (27.1%, p < 0.001 OR 5.27, 95% CI 2.72-10.68).
      DISCUSSION: A high rate of patients with subconjunctival hemorrhage presented
      additional injuries. Visual acuity < 1 increased probability of having additional
      damage. It is suggested that visual acuity be evaluated in every injured eye,
      even when diagnosis of subconjunctival hemorrhage is evident and data of open
      globe absent, to help detect eyes that require specialized evaluation.

PMID- 19764135
TI  - [Long-term stability with absorbable plates and internal fixation in orthognatic
      surgery].
AB  - The author presents his experience using biodegradable self-reinforced
      polylactide (SR-PLLA) plates, and screws in orthognathic surgery to fixate
      horizontal and segmentary osteotomies of maxillae in 142 cases. Experience was
      confirmed by using the same elements to treat acute fractures, old fractures, and
      craniodisostosis for a total of 208 cases with maximum follow-up of 8 years.
      Characteristics of these materials are described, as well as the method used to
      place them; indications and complications are observed.

PMID- 19764136
TI  - [Commentary on the work: "Long-term stability with absorbable plates and internal
      fixation in orthognatic surgery"].

PMID- 19764137
TI  - Is there an indication for palliative surgical procedure of shoulder and upper
      limb malignancies?
AB  - AIMS: Major amputation is not a frequent procedure at present, however, there is
      a group of patients still considered for these treatments. Our objective was to
      evaluate the results of this surgical intervention as well as to evaluate
      morbidity, local control, free disease, and palliation. METHODS: The study
      included 57 patients on whom interscapulothoracic disarticulation (STDI) was
      carried out at the Instituto Nacional de Cancerologia were (Mexico City) from
      1974 to 1993. Patients with oncologic pathology were operated with a palliative
      aims. Twenty eight male and twenty nine female patients were found with average
      age of 44 years (range: 13 to 79 years). Clinical situation was characterized by
      tumor (100%), pain (46%), functional incapacity (39%), ulceration (32%), and
      bleeding (9%), Karnofsky 80% (range, 50 to 100). Time of evolution was 25 months
      (range: 1-121 months) and size was > 10 cm in 86% of cases. RESULTS:
      Postoperative complications were present in ten, followed by patients follow
      infection in five cases, hematoma in the upper lung lobe in two and femoral
      thrombosis, skin wound necrosis, and bleeding in one case each. Palliation was
      evaluated to eliminate tumoral load, ulceration, bleeding, functional incapacity,
      and pre- and postoperative pain. Global survival was 12 months (range, 1-139
      months). CONCLUSIONS: Interscapulothoracic disarticulation is an infrequently
      performed surgery with low morbidity and mortality, low recurrence, no effect on
      survival, and excellent palliative results.

PMID- 19764138
TI  - [Intraabdominal hypertension and abdominal compartment syndrome in patients with
      acute pancreatitis].
AB  - BACKGROUND: Intra-abdominal pressure rises in some circumstances and can cause
      abdominal compartment syndrome. Severe acute pancreatitis frequently causes
      abdominal compartment syndrome. OBJECTIVE: Our objective was to identify the
      relationship between severity of pancreatitis and abdominal pressure. MATERIAL
      AND METHODS: From September 2001 to September 2002, all patients with acute
      severe pancreatitis were included in the study; exclusion was effected with
      history of abdominal surgery for pancreatitis or ventral hernias. In all
      patients, we carried out laboratory tests to establish ranson criteria, Apache II
      score, and indirect measurement of abdominal pressure. Lineal regression and chi
      square test were done. RESULTS: A total of 25 patients was included, 10 men and
      15 women, average age 49.4 years, 11 with mild pancreatitis and 14 with severe
      acute pancreatitis. Abdominal pressure was 2 to 19 cm H2O. On statistic analysis,
      there was strong positive correlation between Apache II score and IAP and 0.781
      of correlation coefficient and 99.5% confidence interval.

PMID- 19764139
TI  - [Perinatal result with conservative treatment in preeclampsia-eclampsia].
AB  - INTRODUCTION: Conservative treatment in severe preeclampsia has been documented
      by several authors citing significant improvement in neonatal outcome lacking a
      significant increase in maternal complications. OBJECTIVE: Our objective was to
      inform of our preliminary results using protocolized conservative management in
      women with preeclampsia-eclampsia, favoring better neonate conditions. MATERIAL
      AND PATIENTS: We included 34 patients with average age of 28.2 years with
      documented severe preeclampsia-eclampsia complicating a 36-weeks or less
      pregnancy, admitted in the obstetric intensive care unit (OICU) between October
      2001 and February 2002. Patients received protocolized management consisting of
      intravascular colume expansion, anti-hypertensive control, target organ
      protection, monitoring, and clinical observation. We considered conservative
      management as a 24 or more period offered to patients with satisfactory response
      to medical treatment and no evidence of binomial compromise. RESULTS: Of our
      group, 85% corresponded to severe preeclampsia, 9% to eclampsia, 3% to imminence
      of eclampsia, and 3% to HELLP syndrome. Average stay in OICU was 5.5 days with
      3.5 days average management before pregnancy was interrupted. These patients
      presented mean gestational age of 32.8 weeks during which we observed anemia, low
      platelets, D dimmer increments, MAP average of 112.8, PCOc 18.6, and BI 0.15. We
      obtained 36 live newborns of whom 12% four died, two were extremely immatures
      (510 g and 600 g, respectively); one 980-g newborn presented intraventricular
      hemorrhage, and a 1,450-g newborn had multiple organ failure. Conservative
      treatment in patients with severe preeclampsia-eclampsia is a feasible
      alternative in hospitals with an ICU. Conservative management can improve
      neonatal survival and prognosis in preterm newborns.

PMID- 19764140
TI  - [Patient satisfaction with surgery in a municipal major out-patient surgery
      program].
AB  - OBJECTIVE: Our objective was to know rate of general and specific satisfaction of
      patients going through major out-patient surgery (MOPS), to determine the
      relationship between satisfaction and sociodemographic variables, and to
      ascertain the influence that MOPS can exert on certain facets of the care
      relationship, user valoration of health services, and out-patient method
      characteristics. SITE: Primary-care polyclinic and secondary-care municipal
      hospital. DESIGN: We conducted a descriptive, qualitative transversal study by
      means of anonymous questionnaires answered by out-patients at home. RESULTS: The
      questionnaires, considered due to its credible and valid characteristics, was
      applied by drained personnel to 83 persons by simple random sanepling to the
      forget population. The majority of out-patients stated that they were very
      (51.81%) or quite (31.12%) satisfied with the method, independently of age, sex,
      place of origin, educational lave, and occupation. A statistical relationship was
      found between general satisfaction and the occurrence of postoperative
      complications, the possibility given to the patient of choosing between in- and
      out-patient surgery, and specific satisfaction with medical care received at he
      hospital and at home. These and then results are discussed and compared whit
      experiences in other fields. In conclusion, patients expressed satisfaction with
      the MOPS program linked with primary health care (PHC), although they stated that
      some aspects of MOPS should be improved.

PMID- 19764141
TI  - [Vasopressin for treatment of shock].
AB  - INTRODUCTION: Vasodilatory refractory shock is common in patients with severe
      burns. It is defined by resistance to high doses of volume and vasopressor
      therapy. OBJECTIVE: Our objective was to investigate effects of vasopressin
      therapy in severe burn patients with vasodilatory refractory shock. PATIENTS AND
      METHODS: We carried out an open, prospective study in 15 patients with severe
      burns with vasodilatory refractary shock. Patients were monitored with arterial
      line, pulmonary artery catheter, transtoracic echocardiography, arterial and
      central venous gases, gastric-arterial CO2 gradient, serum and urinary
      osmolality, urinary electrolytes, dieresis, and trooping T and CPK-MB levels. All
      patients were cultivated. Vasopressin was used in continuous infusion at 0.04
      IU/min for 72 h. Measurements of hemodynamic and metabolic parameters were
      recorded at 2, 4, 8, 12, 24, 48, 72 and 96 h. During treatment with vasopressin,
      therapy with pressor amines was determined and reduced by hemodynamic evolution.
      At the end of 72-h infusion, vasopressin was slowly tapered in 24 h. RESULTS:
      After administration of vasopressin, systemic vascular resistance index (SVRI)
      and pre-arrest morbidity (PAM) were significantly increased (p < 0.05). We
      observed a significant decrease in dopamine and norepinephrine requirements (p <
      0.005). Norepinephrine was discontinued at 72 h and dopamine infusion was
      continued at low dose. Urine output, urinary sodium, and serum bicarbonate were
      significantly increased. deltaCO2 was increased and this finding was associated
      to decrease in norepinephrine and dopamine requirements; this effect translated
      in to better splachnic perfusion. Left ventricular function indexes were normal.
      Patients did not develop evidence of myocardial, splachnic, or limb ischemia
      during vasopressin infusion. In all patients vasopressin was weaned at 24 h and
      removed. In five patients, it was necessary to reinitiate vasopressin infusion
      for another 96 h without complications. Low-dose vasopressin infusions (0.04
      IU/min), are a useful therapy to severely burned patients with vasodilatory
      refractary shock and who are devoid of adverse effects.

PMID- 19764142
TI  - [Hemobilia: a case, complications, follow-up].
AB  - INTRODUCTION: Therapy implies beneficial and adverse reactions and consequences
      presented in this patient who hand hemobilia syndrome and life-threatening
      systemic complications. CASE PRESENTATION: Clinical retrospective study of a 59
      year-old female with multiparity, blood type A Rh (-) who was admitted in
      clinical condition with syndromatic diagnosis of mixed shock, acute abdomen,
      obstructive and/or hepatocellular jaundice, pre-renal hyperazohemia with olyguria
      leading to multiple organ failure requiring surgical and intensive care
      treatment. DISCUSSION: In this case, life-threatening complications due to
      reanimation from state of shock delayed urgent laparotomy for acute abdomen
      finding and treating hemobilia with cholecistostomy with long-term external
      biliary drainage. In multiple organ and system failure syndrome, it was important
      to identify, prevent, and/or treat physiopathologic complications with available
      resources to recover patient health patient. We made observations concerning
      recovery and follow-up.

PMID- 19764143
TI  - [Chronic invasive rhinocerebral mucormycosis].
AB  - Rhinocerebral mucormycosis is a fulminant fungal disease that typically presents
      acutely in patients with diabetic ketoacidosis or immunosuppression. The case of
      a 55 year-old male patient is presented; the patient experienced chronic
      infection that involved nose, paranasal sinuses, hard palate, orbit,
      pterygopalatine fossa, infratemporal fossa with cavernous sinus thrombosis and
      compression of the internal carotid artery which develops in insidious manner
      after metabolic imbalance with predominantly ocular symptoms. The patient was
      managed with Amphotericin B and radical surgical debridement of affected tissue,
      the patient presenting cure without complications or added disabilities.

PMID- 19764144
TI  - [Paraneoplastic syndromes. Associated with lung cancer].
AB  - Paraneoplastic syndromes are disorders of host organ function occurring at a site
      remote from the primary tumor and its metastases. Paraneoplastic syndromes
      associated with primary lung cancer are not uncommon, have diverse initial
      manifestations, and epitomize the systemic nature of human malignant disease. The
      spectrum of clinical features in patients with paraneoplastic syndromes is very
      wide. Although diagnosis is often one of exclusion, improved understanding of the
      pathogenesis involved in some of these syndromes has provided another means of
      recognizing these disorders and perhaps treating affected patients. In this
      update, we review paraneoplastic syndromes associated with lung cancer, potential
      mechanisms, clinical manifestations, diagnosis, and treatment.

PMID- 19764145
TI  - [Speech for the Solemn Session of work initiation of the 70th Academic year,
      Mexican Academy of Surgery].

PMID- 19764146
TI  - The NCCN clinical practice guidelines in oncology: a primer for users.
AB  - Guidelines are becoming increasingly important as potential tools in improving
      clinical decision making. Because oncology practice encompasses a large number of
      tumors and their variants and because each tumor is characterized by
      heterogeneous presentations and clinical evolutions, an oncology guidelines
      program must be large in scope. Oncology practice is slowly moving toward
      evidence-based status, but guideline developers still must rely on less than
      perfect information to achieve this scope. By formalizing the consensus process,
      the NCCN program relies on the expertise of a broad range of cancer specialists
      to interpret the major clinical studies and apply their evaluative skills in
      assessing the relevance of these studies to clinical practice. In areas in which
      data are meager or contradictory, these experts are still charged with making
      recommendations if they believe their collective clinical experience points to a
      reasonable approach to disease management. It follows, therefore, that guidelines
      represent one of the most dynamic areas in medicine. The annual review process is
      designed to incorporate change as new evidence or innovative therapies become
      available. Therefore, the guidelines should be a true reflection of the state-of
      the-art in oncology. The ultimate goal, as always, is improving care for the
      cancer patient.

PMID- 19764147
TI  - Esophageal cancer. Clinical practice guidelines in oncology.
AB  - Esophageal cancer is a major health hazard in many parts of the world. The
      incidence of adenocarcinoma is rising in white men, particularly in the
      nonendemic areas, such as the West. Barrett's metaplasia, gastroesophageal
      reflux, hiatal hernia, and obesity are thought to play a role in these cases. In
      addition, the most common location of esophageal carcinoma has shifted to the
      lower third of the esophagus. Unfortunately, esophageal carcinoma is often
      diagnosed late; therefore, most therapeutic approaches are palliative. Advances
      have been made in staging procedures and in therapeutic approaches. The NCCN
      Esophageal Cancer Guidelines emphasize that palpable advances have been made in
      the treatment of locoregional esophageal carcinoma. Similarly, endoscopic
      palliation of esophageal carcinoma has improved substantially due to improving
      technology. A number of new chemotherapeutic agents are on the horizon including
      antireceptor agents, vaccines, gene therapy, and antiangiogenic agents. The panel
      expects numerous advances in the treatment of esophageal carcinoma in the future.

PMID- 19764148
TI  - Gastric cancer. Clinical practice guidelines in oncology.
AB  - Gastric cancer is rampant in several countries around the world. Its incidence in
      the West has been on the decline for more than 40 years; however, the location of
      gastric cancer has shifted proximally in the past 15 years. The reason for this
      shift is not clear. Diffuse histology is also more common now than intestinal
      type of histology. Advances have been made in staging procedures such as
      laparoscopy and endoscopic ultrasonography and in possible functional imaging
      techniques. The current TNM classification requires an examination of at least 15
      lymph nodes; therefore, at least a D1 dissection is recommended. Patients with
      locoregional gastric carcinoma should also be referred to high-volume treatment
      centers. Combination chemotherapy and radiotherapy in the adjuvant setting for
      select group of patients is considered the new standard in the United States. The
      NCCN Gastric Cancer Guidelines portray uniformity in the systemic approach to
      cancer in the United States. We look forward to the results of investigations of
      a number of new chemotherapeutic agents, including antireceptor agents, vaccines,
      gene therapy, and antiangiogenic agents. The panel anticipates many advances in
      the treatment of esophageal carcinoma in the future.

PMID- 19764149
TI  - Colon cancer. Clinical practice guidelines in oncology.
AB  - The NCCN Colon/Rectal/Anal Cancers Guidelines panel believes that a
      multidisciplinary approach is necessary for managing colorectal cancer. The panel
      endorses the concept that treating patients in a clinical trial has priority over
      standard or accepted therapy. The recommended surgical procedure for resectable
      colon cancer is an en bloc resection. For patients with stage III disease, 5-FU
      based adjuvant therapy is recommended. A patient who has metastatic disease in
      the liver or lung should be considered for surgical resection if he or she is a
      candidate for surgery and if surgery can extend survival. Surgery should be
      followed by adjuvant chemotherapy. The panel advocates a conservative post
      treatment surveillance program for colon carcinoma patients. Serial CEA
      determinations are appropriate if the patient is a candidate for aggressive
      surgical resection should recurrence be detected. Abdominal and pelvic CT scans
      should be used only when there are clinical indications of possible recurrence.
      Patients whose disease progresses during 5-FU-based therapy should be treated
      with bolus irinotecan. Patients who progress on irinotecan are candidates for 5
      FU/leucovorin/oxaliplatin therapy or should be encouraged to participate in a
      phase I or phase II clinical trial.

PMID- 19764150
TI  - Rectal cancer. Clinical practice guidelines in oncology.
AB  - The NCCN Rectal Cancer Guidelines panel believes that a multidisciplinary
      approach is necessary for treating patients with colorectal cancer. Patients with
      T1 or T2 lesions that are node negative by endorectal ultrasound and who meet
      carefully defined criteria can be managed with a transanal excision. Abdominal
      peritoneal resection or low anterior resection with total mesorectal excision is
      appropriate for all other rectal lesions. Either preoperative chemoradiation or
      postoperative chemoradiotherapy is standard for patients with suspected or proven
      serosal invasion (pT3) or regional node involvement. Patients with recurrent
      localized disease should be considered for resection with or without
      radiotherapy. Chemotherapy regimens using irinotecan or oxaliplatin should be
      considered for patients with distant metastasis. The panel endorses the concept
      that treating patients in a clinical trial has priority over standard or accepted
      therapy.

PMID- 19764151
TI  - Anal canal cancer. Clinical practice guidelines in oncology.

PMID- 19764152
TI  - Colorectal cancer screening. Clinical practice guidelines in oncology.

PMID- 19764153
TI  - Hepatobiliary cancer. Clinical practice guidelines in oncology.

PMID- 19764154
TI  - Oncology drug review process.
AB  - The U.S. Food and Drug Administration facilitates the development of drugs
      intended to treat cancer and other serious or life-threatening diseases. This
      article describes the new drug application (NDA) process, endpoints used in
      oncologic trials, and recent initiatives to expedite the review of drugs used to
      treat serious and life-threatening diseases. The Food and Drug Administration can
      grant either regular or accelerated marketing approval for oncology drugs.
      Regular approval is based on endpoints demonstrating that the drug provides a
      clinical benefit, such as longer life, enhanced quality of life, or a favorable
      effect on an established surrogate for longer or better life, such as long-term
      complete responses. Accelerated approval is based on a surrogate endpoint that is
      less well established but is reasonably likely to predict a longer or better life
      and can be granted for drugs that are intended to treat a serious or life
      threatening illness and that provide meaningful therapeutic benefit to patients
      over existing therapies. The Agency classifies an NDA as either a priority or a
      standard application. Drugs that receive priority review are agents that appear
      to represent significant improvements over existing therapies. A priority NDA is
      reviewed by the Agency within 6 months; a standard review is accomplished within
      10 months. The Agency communicates with sponsors throughout the drug development
      process, suggesting appropriate trial designs and meaningful endpoints.

PMID- 19764155
TI  - Controversies in the surgical management of gastric cancer.
AB  - Although the incidence of gastric adenocarcinoma in the United States has
      declined steadily since the early 1900s, it remains a significant health problem.
      Progress has been made during the past few decades in several areas: Lymph node
      staging has been refined, perioperative mortality has fallen, and plausible
      adjuvant therapy has emerged. Currently, complete surgical resection is the
      mainstay of therapy because it is the only potentially curative option; however,
      considerable controversy remains regarding the specifics of a surgical approach.
      This article examines 4 major controversies in the management of gastric cancer:
      extent of gastric resection, role of extended lymph node dissection, value of
      elective splenectomy for proximal gastric lesions, and current state of adjuvant
      therapy. Pertinent retrospective and prospective studies are reviewed to help
      formulate meaningful conclusions.

PMID- 19764156
TI  - New agents for colorectal cancer.
AB  - The past 5 years have seen significant developments in the treatment of
      colorectal cancer (CRC). New chemotherapy agents with activity in CRC have
      demonstrated an improvement in survival for patients with advanced CRC. Studies
      now are focusing on combinations and sequences of chemotherapy agents to prolong
      survival in second- and even third-line therapies. Oral agents have been
      developed and are being studied in combination chemotherapy regimens. Development
      of oral combinations should maintain a survival advantage with the added benefit
      of convenience for the patient. Drugs designed to act on specific cellular
      protein targets have also shown activity and are being explored further.
      Researchers continue to pursue immunotherapy and vaccine therapy. Studies are now
      focusing on how best to use the available agents. These new agents and new
      combinations of agents and of approaches have led and should continue to lead to
      improved outcomes in the treatment of patients with CRC.

PMID- 19764157
TI  - The genetics of hereditary non-polyposis colorectal cancer.
AB  - Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant
      condition accounting for 3% to 5% of all colorectal cancer. HNPCC is caused by
      germline mutations in the mismatch repair system and is recognized by a
      characteristic clinical phenotype as well as a hallmark of the tumors termed
      "microsatellite instability." Microsatellite instability serves as a molecular
      fingerprint for defective mismatch repair and has proven to be useful in the
      molecular diagnostic workup for HNPCC. The crystal structure of the DNA mismatch
      repair protein MutS has been solved, providing insight into the molecular basis
      of defective mismatch repair. Genetic testing has become a key component of the
      treatment of patients and families with HNPCC, and enhanced surveillance for
      HNPCC has been shown to reduce the rate of colorectal cancer by more than half
      and improve 10-year survival from 68% to 93%.

PMID- 19764158
TI  - [Neuroendocrine tumours of the alimentary tract--history and at present].
AB  - Histological classification of the neuroendocrine tumours ("carcinoids") of the
      alimentary tract, as well as the opinion on biological behaviour of these
      tumours, changed rapidly within the last decade. Advances in knowledge of
      cellular biology of the diffuse endocrine system and in clinical diagnostics and
      treatment of tumours lead to the creation of a new histological classification of
      neuroendocrine tumours. This classification, apart from essential histological
      picture and immunohistological characterisation of the markers of neuroendocrine
      differentiation, also includes definition of biological properties of tumours
      based on their site of origin, mitotic and proliferative activity of the tumour
      cells and clinicopathological correlation, including the size of the tumour and
      its progression. Exact classification of an individual tumour into a
      corresponding category is an essential condition to select adequate following
      diagnostic procedures and optimal therapeutic strategy.

PMID- 19764159
TI  - [Systemic amyloidoses in renal biopsy samples].
AB  - The kidneys are one of the most frequent sites of amyloid deposition during
      systemic AL, AA, and several hereditary amyloidoses. Distinguishing between
      different forms of amyloids is clinically important because of their different
      treatment. MATERIAL AND METHODS: We present a 5-year retrospective study of
      amyloidoses diagnosed in renal biopsy samples. The classification of amyloidosis
      was made by immunofluorescence and immunohistochemical staining with antibodies
      to kappa and lambda immunoglobulin light chains, and for serum amyloid A protein.
      RESULTS: From January 2003 to December 2007, 996 renal biopsy samples from one
      centre were evaluated. Amyloidosis was diagnosed in 62 samples (6.2%); 33 (53.2%)
      were classified as AL and 25 (40.3%) as AA amyloidosis. Four cases have remained
      unclassified. We did not identify any difference in the distribution of deposits
      among cases with AL and AA amyloidosis, respectively. The majority of patients
      underwent the renal biopsy due to severe proteinuria or nephrotic syndrome. Three
      patients had very low proteinuria, less than 0.5 g/day. Diagnosis of amyloidosis
      was suspected by nephrologists in 48 patients (77.4%). CONCLUSION: Diagnosis of
      amyloidosis involves detection of amyloid deposits and classification of the
      amyloid form, which represent the basic step for appropriate therapy. Altogether
      it is not an easy task for pathologists, and with the emergence of markedly
      different treatments depending on the specific type of amyloid, the precise
      typing is of increasing clinical importance and should be performed with great
      care. Immunofluorescence can be very useful in daily practice for classification
      of the type of amyloidosis.

PMID- 19764160
TI  - Angiosarcoma of the parotid gland.
AB  - Angiosarcomas of the major salivary glands are rare tumours. The authors describe
      a case of the tumour located in the right parotid gland of a 77-year-old woman.
      Histological examination revealed a poorly differentiated tumour made up of
      epithelioid and spindle cells. These two types of cells intermingled. In some
      parts, primitive mutually anastomosing irregularly shaped vascular spaces with
      atypical endothelial cells were found. The tumour cells were positive for CD31,
      CD34, EMA and FVIII (focally). Due to the relatively short follow-up period the
      prognosis of the disease is difficult to estimate.

PMID- 19764161
TI  - [Retiform hemangioendotelioma in a 8-year-old girl--case report].
AB  - Retiform hemangioendothelioma (RHE) is a rare vascular tumoriform lesion
      characterized by rete testis--like vascular structures. RHE belongs to a group of
      vascular tumors of intermediate malignancy and together with Dabska tumor form a
      category of so-called hobnail hemangioendotheliomas. Authors present a case of a
      8-year-old girl with RHE which was located in right calf and measured 12 x 8 mm.
      Histologically, the tumor consisted of a net of vessel formations with retiform
      appearance and prominent endothelial nuclei. Some of vascular channels had
      intraluminal projections. Other benign and malignant vascular lesions with
      hobnail cells (hemangioma, angiosarcoma) have to be considered in differential
      diagnosis.

PMID- 19764162
TI  - [Perforating folliculitis. Case report and differential diagnosis].
AB  - A 26-year-old woman suddenly noticed an onset of disseminated papular exanthema
      during her institutional treatment for alcohol abuse. After 9 weeks of slowly
      progressive course a dermatologist was consulted, who suggested a diagnosis of
      pityriasis lichenoides. Skin biopsy revealed cystical enlargement of hair
      follicles that were filled up with keratinous and parakeratotic masses
      interspersed with particles of fragmented collagen. Numerous inflammatory cells
      were present within the lesion. Many focal perforations of infundibular
      epithelium draining a cellular debris were prominent. Severely disturbed
      follicles were engulfed by giant cell inflammatory infitrate containing remnants
      of collagen and elastic fibers. Considering all the histopathologic findings and
      clinical course, the case was finally diagnosed as perforating folliculitis, a
      distinct type from the family of perforating dermatoses.

PMID- 19764163
TI  - Recurrent mucinous carcinoma of skin mimicking primary mucinous carcinoma of
      parotid gland: a diagnostic pitfall.
AB  - A case of a 63-year-old man with a swelling lasting 2 years in the left
      infraauricular area is reported. Examination by fine needle aspiration cytology
      raised suspicion of mucoepidermoid or adenoid cystic carcinoma of the parotid
      gland and an excision was recommended. The lateral parotidectomy specimen showed
      a poorly circumscribed gelatinous tumor measuring 15 mm in diameter within the
      parotid gland tissue. Microscopically, the lesion featured large pools of mucin
      containing clusters of tumor cells with little atypia and low mitotic activity.
      Immunohistochemically, the tumor cells showed expression of epithelial markers
      and of both estrogen and progesterone receptors. Left lateral neck dissection
      revealed massive lymphogenous dissemination of the tumor. Retrospective analysis
      of a skin biopsy from the same anatomic area performed 8 years prior to parotid
      neoplasm displayed a tumor with identical microscopic appearance and
      immunohistochemical profile (additionally performed) which was, however,
      misdiagnosed as a benign lesion. The diagnosis of recurrent primary mucinous
      carcinoma of the skin infiltrating the parotid gland was established. The patient
      underwent radiotherapy and has been 3 years free of disease. The differential
      diagnostics of this rare tumor is discussed.

PMID- 19764164
TI  - [What is your diagnosis? Metastasis of well-differentiated carcinoma in lymph
      nodes of the neck with significant myofibroblastic proliferation and
      discontinuous basal membrane].

PMID- 19764165
TI  - [How to improve diagnosis of systemic amyloidosis in clinical practice].

PMID- 19764166
TI  - The other side of the coin.

PMID- 19764167
TI  - Efficacy of linear frequency transposition on consonant identification in quiet
      and in noise.
AB  - BACKGROUND: Frequency transposition has gained renewed interest in recent years.
      This type of processing takes sounds in the unaidable high-frequency region and
      moves them to the lower frequency region. One concern is that the transposed
      sounds mask or distort the original low-frequency sounds and lead to a poorer
      performance. On the other hand, experience with transposition may allow the
      listeners to relearn the new auditory percepts and benefit from transposition.
      PURPOSE: The current study was designed to examine the effect of linear frequency
      transposition on consonant identification in quiet (50 dB SPL and 68 dB SPL) and
      in noise at three intervals--the initial fit, after one month of use (along with
      auditory training), and a further one month of use (without directed training) of
      transposition. RESEARCH DESIGN: A single-blind, factorial repeated-measures
      design was used to study the effect of test conditions (three) and hearing aid
      setting/time interval (four) on consonant identification. STUDY SAMPLE: Eight
      adults with a severe-to-profound high-frequency sensorineural hearing loss
      participated. INTERVENTION: Participants were fit with the Widex m4-m behind-the
      ear hearing aids binaurally in the frequency transposition mode, and their speech
      scores were measured initially. They wore the hearing aids home for one month and
      were instructed to complete a self-paced "bottom-up" training regimen. They
      returned after the training, and their speech performance was measured. They wore
      the hearing aids home for another month, but they were not instructed to complete
      any auditory training. Their speech performance was again measured at the end of
      the two-month trial. DATA COLLECTION AND ANALYSIS: Consonant performance was
      measured with a nonsense syllable test (ORCA-NST) that was developed at this
      facility (Office of Research in Clinical Amplification [Widex]). The test
      conditions included testing in quiet at 50 dB SPL and 68 dB SPL, and at 68 dB SPL
      in noise (SNR [signal-to-noise ratio] = +5). The hearing aid conditions included
      no transposition at initial fit (V1), transposition at initial fit (V2),
      transposition at one month post-fit (V3), and transposition at 2 months post-fit
      (V4). Identification scores were analyzed for each individual phoneme and
      phonemic class. Repeated-measures ANOVA were conducted using SPSS software to
      examine significant differences. RESULTS: For all test conditions (50 dB SPL in
      quiet, 68 dB SPL in quiet, and 68 dB SPL in noise), a statistically significant
      difference (p < 0.05 level) was reached between the transposition condition
      measured at two months postfitting and the initial fitting (with and without
      transposition) for fricatives only. The difference between transposition and the
      no-transposition conditions at the 50 dB SPL condition was also significant for
      the initial and one-month intervals. Analysis of individual phonemes showed a
      decrease in the number of confusions and an increase in the number of correct
      identification over time. CONCLUSIONS: Linear frequency transposition improved
      fricative identification over time. Proper candidate selection with appropriate
      training is necessary to fully realize the potential benefit of this type of
      processing.

PMID- 19764168
TI  - Comparison of vent effects between a solid earmold and a hollow earmold.
AB  - BACKGROUND: Hollow earmolds have become a popular type of earmold used in thin
      tube, microsize hearing aid fittings. It is desirable for clinicians to be
      familiar with their characteristics and limitations. PURPOSE: This investigation
      compared the effects of vent diameter between a traditional solid earmold and a
      hollow earmold that is used in modern thin-tube hearing aid fittings. RESEARCH
      DESIGN: A single-blind, 2 x 4 factorial design was used. STUDY SAMPLE: Eight
      adults with a high-frequency hearing loss participated. INTERVENTION: Custom
      earmolds for use with thin-tube hearing aids were made for each participant. Two
      types of earmolds were made: a solid earmold with a traditional vent length and a
      hollow earmold where the thickness of the shell was the length of the vent. Vent
      diameters were 0, 1, 2, and 3 mm. DATA COLLECTION AND ANALYSIS: The vent effect
      was evaluated on real-ear aided response, real-ear occluded response during
      vocalization, subjective occlusion rating, insertion loss, and maximum available
      gain before feedback. Real-ear measurements were made with the Fonix 6500 probe
      microphone real-ear system. Vocalizations from the participants were analyzed
      with a custom MATLAB program, and statistical analysis was conducted with SPSS
      software. RESULTS: A systematic vent effect was seen with each earmold type as
      the nominal vent diameter changed. For the same vent diameter, the vent effect
      seen with the hollow earmold was greater than that of the solid earmold.
      CONCLUSIONS: Because of the difference in vent length (and thus acoustic mass)
      between a solid and a hollow earmold, the effect of vent diameter in a hollow
      earmold is more pronounced than that seen in a solid earmold of the same nominal
      vent diameter. Thus, a smaller vent diameter will be needed in a hollow earmold
      than in a solid earmold to achieve similar vent effects.

PMID- 19764169
TI  - Morphological changes in the middle latency response using maximum length
      sequence stimuli.
AB  - BACKGROUND: The middle latency response (MLR) can be a powerful tool for
      assessing integrity of cortical and subcortical auditory structures. Most
      research on the MLR, however, is constrained to relatively slow repetition rates
      by the time window necessary for response acquisition. Maximum length sequence
      (MLS) paradigms enable the recording of the MLR at high repetition rates, which
      could reduce test time and provide information about the behavior of auditory
      structures at rapid rates of stimulation. PURPOSES: To examine potential timing
      advantages and differences in waveforms between an MLS-MLR paradigm compared to a
      conventional MLR paradigm (Experiment 1), and to examine effects of rate on MLR
      morphology within the MLS paradigm (Experiment 2). RESEARCH DESIGN: A repeated
      measures study. All subjects within each experiment underwent every condition for
      that experiment. STUDY SAMPLE: Ten young adult female subjects participated in
      each experiment of this study. All subjects had normal hearing and negative
      neurological history. DATA COLLECTION AND ANALYSIS: Latency and amplitude values
      as well as the presence/absence of Na, Pa, Nb, and Pb components of the MLR were
      measured. Comparisons were made between the MLS-MLR and conventional MLR
      paradigms, as well as between repetition rates within the MLS-MLR paradigm.
      RESULTS: Significant latency and amplitude differences were found between MLS and
      conventional MLR paradigms. The late components of the MLR (Nb, Pb) were present
      significantly more often when the MLS paradigm was used. No timing advantage was
      found with the MLS-MLR paradigm. Within the MLS paradigm, as repetition rate
      increases, latency becomes significantly shorter and amplitude significantly
      lower. CONCLUSIONS: Middle latency responses evoked by the MLS-MLR paradigm show
      significant differences from those evoked by a conventional MLR paradigm. The MLS
      MLR paradigm can reliably evoke the late components (Nb, Pb) of the MLR and may
      be an important clinical tool for future investigation of these elements.

PMID- 19764170
TI  - Observations on hearing aid users' strategies for controlling the level of their
      own voice.
AB  - BACKGROUND: Evidence suggests that hearing-aid users have difficulties with own
      voice level control, most likely because their auditory feedback is affected by
      hearing-aid amplification. PURPOSE: The purpose of this study was to investigate
      how changes to auditory feedback affect the voice level of hearing-aid users.
      RESEARCH DESIGN: A correlational study was set up to investigate the relation
      between voice level and hearing-aid amplification. STUDY SAMPLE: Seven hearing
      impaired speakers participated. All were experienced hearing-aid users. DATA
      COLLECTION AND ANALYSIS: The speakers projected their voice to a passive listener
      across different speaker-listener distances and with different prescriptions of
      gain in an experimental hearing aid. For each combination of conditions, produced
      voice level and self-perceived voice level was measured. These data were
      subjected to an analysis of variance assuming a mixture of random and fixed
      effects. In addition, all speakers took part in interviews. RESULTS: Three
      speakers reacted to the changes in auditory feedback in agreement with previous
      experiments with normal-hearing speakers: they compensated by changing produced
      voice level. In contrast, the voice levels in the other four speakers were
      largely unaffected by the changes to auditory feedback. A secondary observation
      was that while all speakers increased their voice level with distance, the two
      subgroups produced different growth rates of vocal level versus distance.
      CONCLUSIONS: It is hypothesized that the speakers in the former subgroup relied
      on auditory feedback for solving the experimental task, whereas the latter
      subgroup had developed an own-voice level-control strategy based on
      proprioceptory feedback, possibly because they have lost faith in their auditory
      feedback mechanism, which indeed is changed by both hearing loss and hearing-aid
      amplification. Comparison to "target" voice levels suggests that proprioceptory
      feedback is less effective than auditory feedback for achieving adequate level
      distance growth rate.

PMID- 19764172
TI  - The science of carbs.

PMID- 19764171
TI  - Vestibular evoked myogenic potential (VEMP) testing: normative threshold response
      curves and effects of age.
AB  - BACKGROUND: Vestibular evoked myogenic potential (VEMP) testing has gained
      increased interest in the diagnosis of a variety of vestibular etiologies.
      P13/N23 latency, amplitude and threshold response curves have been used to
      compare pathologic groups to normal controls. Appropriate characterization of
      these etiologies requires normative data across the frequency spectrum and age
      range. PURPOSE: The objective of the current study was to test the hypothesis
      that significant changes in VEMP responses occur as a function of increased age
      across all test stimuli as well as characterize the VEMP threshold response curve
      across age. RESEARCH DESIGN: This project incorporated a prospective study design
      using a sample of convenience. Openly recruited subjects were assigned to groups
      according to age. STUDY SAMPLE: Forty-six normal controls ranging between 20 and
      76 years of age participated in the study. Participants were separated by decade
      into five age categories from 20 to 60 plus years. Normal participants were
      characterized by having normal hearing sensitivity, no history of neurologic or
      balance/dizziness involvement, and negative results on a direct office vestibular
      examination. INTERVENTION: VEMP responses were measured at threshold to click and
      250, 500, 750, and 1000 Hz tone burst stimuli and at a suprathreshold level to
      500 Hz toneburst stimuli at123 dB SPL. DATA COLLECTION AND ANALYSIS: A mixed
      group factorial ANOVA (analysis of variance) and linear regression were performed
      to examine the effects of VEMP characteristics on age. RESULTS: There were no
      significant differences between ears for any of the test parameters. There were
      no significant differences between age groups for n23 latency or amplitude in
      response to any of the stimuli. Significant mean differences did exist between
      age groups for p13 latency (250, 750, and 1000 Hz) and threshold (500 and 750
      Hz). Age was significantly correlated with VEMP parameters. VEMP threshold was
      positively correlated (250, 500, 750, 1000 Hz); and amplitude was negatively
      correlated (500 Hz maximum). The threshold response curves revealed best
      frequency tuning at 500 Hz with the highest thresholds in response to click
      stimuli. However, this best frequency tuning dissipated with increased age. VEMP
      response rates also decreased with increased age. CONCLUSION: We have
      demonstrated that minor differences in VEMP responses occur with age. Given the
      reduced response rates and flattened frequency tuning curve for individuals over
      the age of 60, frequency tuning curves may not be a good diagnostic indicator for
      this age group.

PMID- 19764173
TI  - Better beef.

PMID- 19764174
TI  - Serious competition.

PMID- 19764175
TI  - Gotcha covered.

PMID- 19764177
TI  - On the go.

PMID- 19764176
TI  - Diabetes in the limelight. Interview by Tracey Neithercott.

PMID- 19764178
TI  - On the menu.

PMID- 19764179
TI  - [Obstacles which have hampered the progress of Evidence Based Prevention (EBP).

PMID- 19764180
TI  - Systematic reviews of workplace injury interventions: what are we missing?
AB  - BACKGROUND: There are pitfalls associated with applying a biomedical model with
      its emphasis on experimental designs to the evaluation of workplace injury
      interventions. OBJECTIVES: Evaluation over enough time is essential in
      occupational safety when interventions are expected to have a latent effect as
      well as to assess sustained effects. Controlled trials are not well-suited to
      this task and are not even possible in circumstances where a policy change, such
      as legislative action, affects a population of workers simultaneously. Social
      context influences occupational injury interventions, their evaluation and the
      wider generalization of findings but is lost in the pooling of data for meta
      analyses. Some of these issues can be addressed through recognition of the
      contribution of diverse observational methodologies in intervention evaluation,
      improvement and maintenance of robust surveillance systems, and inclusion of
      qualitative methodologies not typically embraced by epidemiologists or medical
      researchers. METHODS: Through consideration of an evaluation of a legislative
      effort to prevent falls from height in construction, we demonstrate lack of
      flexibility in current methods used for evaluating time series analyses in
      systematic reviews of occupational injury intervention effectiveness. DISCUSSION
      AND CONCLUSIONS: These include the manner in which downward change in slope is
      assessed and the call to demonstrate a significant initial downward change in
      level. We illustrate essential contextual detail regarding this intervention that
      is lost in the pooling of data from multiple studies into a combined measure of
      effect. This reduction of occupational injury intervention evaluation to one of
      pure statistical significance is ill-conceived, irresponsible, and should be
      stopped.

PMID- 19764181
TI  - Writing a Cochrane systematic review on preventive interventions to improve
      safety: the case of the construction industry.
AB  - OBJECTIVES: The objective of this paper is to describe the main steps and to
      conduct a systematic literature review on preventive interventions concerning
      work-related injuries and to illustrate the process. METHODS: Based on the
      Cochrane handbook, a structured framework of six steps was outlined for the
      development of a systematic review. This framework was used to describe a
      Cochrane systematic review (CSR) on the effectiveness of interventions to prevent
      work related injuries in the construction industry. RESULTS: The 6 main steps to
      write a CSR were: formulating the problem and objectives; locating and selecting
      studies; assessing study quality; collecting data; analysing data and presenting
      results; and interpreting results. The CSR on preventing injuries in the
      construction industry yielded five eligible intervention studies. Re-analysis of
      original injury data of the studies on regulatory interventions, through
      correcting for pre-intervention injury trends led to different conclusions about
      the effectiveness of interventions than those reported in the original studies.
      CONCLUSIONS: The Cochrane handbook for systematic reviews of interventions
      provides a practical and feasible six-step framework for developing and reporting
      a systematic review for preventive interventions.

PMID- 19764182
TI  - [A systematic review of the effectiveness of workplace safety interventions].
AB  - INTRODUCTION: The authors carried out a systematic review of the effectiveness of
      workplace safety interventions, as a part of a wider project funded by CCM,
      Centre for Disease Control. METHODS: Several electronic bibliographic databases
      were checked, using a standardized string selection. The string contained the
      following four items: the intervention; job features; type of injury;
      efficacy/effectiveness. RESULTS: Of the various databases consulted, Web of
      Science was the most efficient. Overall 5531 articles were selected. After
      reading the title and abstract, 4695 were excluded and eventually 35 systematic
      reviews were selected, which synthesized 769 original articles. DISCUSSION AND
      CONCLUSIONS: The main topics of the selected systematic reviews were: certain
      sectors (building industry, agriculture, health care); personal protective
      equipment; work organization and prevention management at plant level; evaluation
      of prevention policies by national and regional authorities. A clear need for
      multiple bibliographical data-base search emerged at the end of this study.

PMID- 19764183
TI  - [Legislation and inspection for the health and safety of workers. Efficacy and
      limits].
AB  - OBJECTIVES: To provide information regarding Occupational Health and Safety (OHS)
      Inspections in Europe. METHODS AND RESULTS: The dynamics that are transforming
      regulatory subsystems and complementary inspection services are described.
      Simplification initiatives, the limits and difficulties of applying the different
      models of Health and Safety Management Systems are discussed. Examples are given
      on how to evaluate legislation and technical standards during planning and
      enforcement. Different approaches for studying characteristics, methodologies and
      efficacy in practice of OHS Inspection are provided. CONCLUSIONS: Targeted
      inspections need to respond to the needs of enterprises and workers. Impartiality
      must be guaranteed and workers' participation should be facilitated.

PMID- 19764184
TI  - [Setting up a national information system for prevention].
AB  - BACKGROUND: The recent law (D.lgs n. 81/2008) redesigned all the Italian
      regulations regarding safety and health at work. It redesigned rules that up to
      now were contained in laws that were introduce over a period of over nearly sixty
      years, with due review and extension. METHODS AND RESULTS: Article 8 of the law
      is dedicated specifically to a national information system for the prevention at
      the workplace (called SINP), created "with the aim of supplying useful data in
      order to guide, programme, to plan, and assess the effectiveness of actions taken
      for the prevention of injuries and occupational diseases... and to provide
      guidance in matters of inspection". It is important to emphasize that the course
      followed to define the SINP is due to the joint efforts that INAIL, ISPESL, the
      Regions and the independent Provinces started in 2002, by agreeing to a protocol,
      with the common aim of creating an integrated information system for prevention
      in the workplace. CONCLUSIONS: At present data are available on a national scale
      and they are useful in order to acquire more detailed knowledge of the area in
      question (on enterprises, accidents, occupational diseases) and in order to
      define intervention priorities, to plan and program activities and verify the
      results.

PMID- 19764185
TI  - [The contribution of the Italian scientific community to efficacy studies in
      Occupational Health (1990-2006)].
AB  - INTRODUCTION: Evidence-based prevention (EBP) is gaining growing interest among
      the international scientific community in the field of Occupational Health. In
      order to ascertain the commitment that has been made in Italy to participation in
      EBPR, we conducted a systematic review of scientific publications on efficacy
      evaluations in Italy. METHODS: We hand-searched journals and interrogated the
      PubMed database to identify reports of studies evaluating interventions designed
      to improve workers' health in Italy between 1990 and 2006. The selected articles
      were classified by institutional category (of the first author), intervention
      methodology, study design, type of risk factor, and occupational sector. RESULTS:
      We found 23 eligible publications in the Italian language and 9 in English. The
      most frequent study-design was pre-/post-intervention evaluation; 3 studies were
      randomized trials. The interventions were aimed mainly at controlling the effects
      of chemical hazards and noise; health-care settings were the most frequent. We
      found only 2 studies (1 in English) evaluating the efficacy of interventions
      targeting injury prevention. DISCUSSION: The systematic approach of EBP can be
      applied to most occupational health interventions. These results may contribute
      to the debate on methodology and outcomes in the scientific community.

PMID- 19764186
TI  - [An injuries prevention programme in the transport and cargo handling sector,
      implemented by the ASL 10 Local Health Unit, Florence].
AB  - BACKGROUND: There are doubts about the ability of public health services to
      significantly reduce occupational injuries through non-targeted investigations
      and surveillance programmes. METHODS: For this reason an intervention was
      designed specifically for the transport and cargo handling sector, in which
      inspections are concentrated on the minority of higher risk companies, followed
      by ex-post assessment of the outcomes. RESULTS AND DISCUSSION: The goal of
      identifying the most hazardous companies through injury data appears to be
      successful in companies with more than 3 employees. Some problems remain for
      smaller companies and for the large porterage cooperatives, where the official
      data on the number of employees is unreliable.

PMID- 19764187
TI  - [Prevention of occupational injuries in foundries: multidisciplinary intervention
      and evaluation of effectiveness].
AB  - BACKGROUND: There is a lack of field studies aimed at reducing occupational
      injuries (OI), particularly in foundries. OBJECTIVES: To evaluate effectiveness
      of multidisciplinary intervention in foundries. METHODS: The study was carried
      out in two foundries (cast-iron=A, non-ferrous=B). Since 1999-2000, a
      multidisciplinary intervention was developed, by a team managed by the
      occupational physician, including safety personnel and workers' representatives.
      Interventions regarded maintenance, protective equipment, procedures, training,
      health surveillance (HS), fitness for work, first aid. The desired outcome was a
      reduction in injury rates. RESULTS: In foundries A and B, respectively 522 and 90
      OI occurred in 1997-2007, accounting for 10,500 and 2,300 lost work days.
      Statistical analysis showed a significant decrease in incidence and frequency in
      both foundries. HS allowed for human factor and fitness for work evaluation,
      return-to-work management. Safety culture, behaviour and procedures positively
      changed. CONCLUSIONS: The study was effective in reducing OI rates and improving
      a number of secondary outcomes. The same intervention, taking into account
      Evidence Based Prevention, is ongoing in about 50 foundries.

PMID- 19764188
TI  - [Effectiveness of a training programme in reducing occupational injuries: the
      Turin-Novara high-speed railway line experience].
AB  - BACKGROUND: There is little evidence in the literature to suggest that safety
      training is effective in reducing injuries at the workplace. OBJECTIVE: This
      study aimed at assessing the impact of a safety training programme on injury
      rates during construction work on the Turin-Novara high-speed railway line (2002
      2006). METHODS: We adopted a before-after study design. Since workers were
      enrolled and trained at different times, pre- and post-training periods were
      calculated individually for each worker RESULTS: At the end of the training
      programme, the incidence of occupational injuries had fallen by 16% in the case
      of basic training and 25% for specific training. In the construction workers
      group (63.5% of trained workers) the reductions were 21% for basic training and
      27% for specific training. All variations were statistically significant.
      CONCLUSION: Implementation of the training programme described led to a reduction
      in injury rates.

PMID- 19764189
TI  - [Effectiveness trial for prevention of occupational injuries in the wood
      processing industry].
AB  - BACKGROUND: Training is a key tool to improve prevention and safety management at
      the workplace. Few studies have aimed at assessing quality of training and its
      outcomes. OBJECTIVES AND METHODS: This paper describes the rationale, design,
      content, and evaluation of an ongoing randomized controlled trial aimed at
      assessing the effectiveness of a training programme designed to reduce the risk
      of occupational injuries among employees of the wood processing industry.
      DISCUSSION AND CONCLUSIONS: Well designed, targeted training programmes could
      represent a feasible means of reducing work injuries by improving employers'
      behaviour and attitudes towards safety; nevertheless, these kinds of
      interventions have a considerable impact both in terms of human resources and in
      terms of cost. For these reasons, assessment of effectiveness and knowledge
      sharing should be considered as essential phases of injury prevention programmes.

PMID- 19764190
TI  - [Occupational physician's decisions on the basis of legislation, ethics and
      scientific evidence].
AB  - BACKGROUND: In the dynamic context of occupational medicine an increasing number
      of occupational health problems requires a high-quality standard practice
      supported by decisions consistent both with ethics and legislation. OBJECTIVES:
      This paper examines the relationship between legal requirements, ethical values
      and scientific evidence issues in occupational health practice. RESULTS: i) Legal
      requirements. Italian law states that practice must be evidence-based and comply
      with the code of ethics for occupational health professionals of the ICOH. ii)
      Ethical values. The code itself emphasizes that practice should be relevant,
      knowledge-based, sound and appropriate to occupational risks. Furthermore, the
      objectives and methods of health surveillance and biological monitoring must be
      clearly defined and indicator must be chosen according to their relevance and
      predictive value. Any dilemma arising from the practice should be dealt with
      according to the ethical principles of health benefit, independence and justice.
      iii) Scientific evidence. Both the law and the code of ethics require that
      practice be based on available evidence. CONCLUSIONS: Decisions made on the basis
      of a comprehensive process founded on scientific evidence should result in
      effective and high-quality outcomes that respect both the law and the rights of
      individuals and society.

PMID- 19764191
TI  - [Efficacy and appropriateness in updating and validating the activities of the
      occupational health physician].
AB  - BACKGROUND: We reviewed the Italian tools for updating and validating the
      activities of occupational health physicians (guidelines, consensus documents,
      technology assessment, good practices, etc.) from the point of view of efficacy
      and appropriateness. RESULTS AND CONCLUSIONS: We examined more than 20 guidelines
      produced since 2003 by the Italian Society of Occupational Health and Industrial
      Hygiene (SIMLII), the procedures issued by the National System of Guidelines in
      Medicine/SNLG) by the Italian National Health Institute (ISS) and the new law on
      occupational safety and health "Decreto Legislativo 81/08", which for the first
      time includes and defines in specific legislation the different possible
      instruments for guiding the activities of the occupational health physician, not
      only to improve the effectiveness of interventions but also aimed at constantly
      adopting rigorous methodologies based on evidence.

PMID- 19764192
TI  - [Malignant mesothelioma of the pleura among Finance Police personnel].

PMID- 19764193
TI  - [Aggregate data and game theory].

PMID- 19764194
TI  - [The pulmonary burden of amphibole asbestos fibers in exposed, deceased workers].

PMID- 19764195
TI  - NEWater future?

PMID- 19764196
TI  - Widely used antifouling biocide lingers in freshwater ecosystems.

PMID- 19764197
TI  - Perfluoropolymer degrades in decades, study estimates.

PMID- 19764198
TI  - Hunting for engineered nanomaterials in the environment.

PMID- 19764199
TI  - Station ALOHA stands sentinel.
AB  - Samples collected near this remote buoy provide an exquisitely detailed record of
      the ocean's changing condition during the past 21 years.

PMID- 19764200
TI  - The Pacific Ocean's acidification laboratory.
AB  - The thermal vents of Maug Island offer a rare chance to study ocean acidification
      in situ, which gives us a glimpse of what the future might hold.

PMID- 19764201
TI  - The University of California Center for the Environmental Implications of
      Nanotechnology.
AB  - Assessing nanomaterialsfor human health and ecotoxicological impact can be well
      aided by using high-throughput laboratory methods.

PMID- 19764202
TI  - Decreasing uncertainties in assessing environmental exposure, risk, and
      ecological implications of nanomaterials.
AB  - Determining the fate and interactions of nanomaterials in complex environmental
      contexts is required to assess exposure and possible harm as well as to inform
      regulation. As the nanotechnology industry moves up into the rarified air of
      trillion dollar economics over the next several years (1), the number of simple
      and complex manufactured nanomaterials (NMs), and their uses, will grow
      tremendously. Large-scale production of engineered NMs presents the possibility
      that organisms and ecosystems may be exposed to new levels and qualities of
      substances with unknown consequences. Naturally occurring nanoscale materials are
      also ubiquitous in the biosphere, comprising the very building blocks of life and
      likely playing an important role in ecosystem

PMID- 19764204
TI  - Life-cycle assessment of biodiesel production from microalgae.
AB  - This paper provides an analysis of the potential environmental impacts of
      biodiesel production from microalgae. High production yields of microalgae have
      called forth interest of economic and scientific actors but it is still unclear
      whether the production of biodiesel is environmentally interesting and which
      transformation steps need further adjustment and optimization. A comparative LCA
      study of a virtual facility has been undertaken to assessthe energetic balance
      and the potential environmental impacts of the whole process chain, from the
      biomass production to the biodiesel combustion. Two different culture conditions,
      nominal fertilizing or nitrogen starvation, as well as two different extraction
      options, dry or wet extraction, have been tested. The best scenario has been
      compared to first generation biodiesel and oil diesel. The outcome confirms the
      potential of microalgae as an energy source but highlights the imperative
      necessity of decreasing the energy and fertilizer consumption. Therefore control
      of nitrogen stress during the culture and optimization of wet extraction seem to
      be valuable options. This study also emphasizes the potential of anaerobic
      digestion of oilcakes as a way to reduce external energy demand and to recycle a
      part of the mineral fertilizers.

PMID- 19764203
TI  - Quantitative analysis of fullerene nanomaterials in environmental systems: a
      critical review.
AB  - The increasing production and use of fullerene nanomaterials has led to calls for
      more information regarding the potential impacts that releases of these materials
      may have on human and environmental health. Fullerene nanomaterials, which are
      comprised of both fullerenes and surface-functionalized fullerenes, are used in
      electronic, optic, medical, and cosmetic applications. Measuring fullerene
      nanomaterial concentrations in natural environments is difficult because they
      exhibit a duality of physical and chemical characteristics astheytransition from
      hydrophobic to polar forms upon exposure to water. In aqueous environments, this
      is expressed as their tendency to initially (i) self-assemble into aggregates of
      appreciable size and hydrophobicity, and subsequently (ii) interact with the
      surrounding water molecules and other chemical constituents in natural
      environments thereby acquiring negative surface charge. Fullerene nanomaterials
      may therefore deceive the application of any single analytical method that is
      applied with the assumption that fullerenes have but one defining characteristic
      (e.g., hydrophobicity). Our findings include the following: (1) Analytical
      procedures are needed to account for the potentially transitory nature of
      fullerenes in natural environments through the use of approaches that provide
      chemically explicit information including molecular weight and the number and
      identity of surface functional groups. (2) Sensitive and mass-selective
      detection, such as that offered by mass spectrometry when combined with optimized
      extraction procedures, offers the greatest potential to achieve this goal. (3)
      Significant improvements in analytical rigor would result from an increased
      availability of well characterized authentic standards, reference materials, and
      isotopically labeled internal standards. Finally, the benefits of quantitative
      and validated analytical methods for advancing the knowledge on fullerene
      occurrence, fate, and behavior are indicated.

PMID- 19764205
TI  - Intercontinental impacts of ozone pollution on human mortality.
AB  - Ozone exposure is associated with negative health impacts, including premature
      mortality. Observations and modeling studies demonstrate that emissions from one
      continent influence ozone air quality over other continents. We estimate the
      premature mortalities avoided from surface ozone decreases obtained via combined
      20% reductions of anthropogenic nitrogen oxide, nonmethane volatile organic
      compound, and carbon monoxide emissions in North America (NA), EastAsia (EA),
      South Asia (SA), and Europe (EU). We use estimates of ozone responses to these
      emission changes from several atmospheric chemical transportmodels combined with
      a health impactfunction. Foreign emission reductions contribute approximately
      30%, 30%, 20%, and >50% of the mortalities avoided by reducing precursor
      emissions in all regions together in NA, EA, SA and EU, respectively. Reducing
      emissions in NA and EU avoids more mortalities outside the source region than
      within, owing in part to larger populations in foreign regions. Lowering the
      global methane abundance by 20% reduces mortality mostin SA,followed by EU, EA,
      and NA. For some source-receptor pairs, there is greater uncertainty in our
      estimated avoided mortalities associated with the modeled ozone responses to
      emission changes than with the health impact function parameters.

PMID- 19764206
TI  - Partial pressures of PCB-11 in air from several Great Lakes sites.
AB  - Relatively high concentrations of 3,3'-dichlorobiphenyl (PCB-11) have been
      reported in water and air, and it has been suggested that this compound did not
      come from commercial PCB products. We report here data on atmospheric partial
      pressures of PCB-11 and of total PCBs at five sites around the Great Lakes and
      demonstrate that both total PCBs and PCB-11 track human population density. In
      addition, we show that with the exception of Chicago, the PCB congener pattern at
      our sampling sites is best represented by Aroclor 1242; in Chicago, the pattern
      is best represented by a 1:1 mixture of Aroclors 1242 and 1254. With the possible
      exception of Sturgeon Point New York, the levels of PCB-11 in air have not
      changed between January 2004 and December 2007. The source of PCB-11 may be
      related to yellow pigments, to the degradation of more highly chlorinated PCB
      congeners, or to both.

PMID- 19764207
TI  - Organic molecular compositions and size distributions of chinese summer and
      autumn aerosols from nanjing: characteristic haze event caused by wheat straw
      burning.
AB  - Size-segregated aerosol samples were collected in urban Nanjing, China during
      summer and autumn of 2007 including a period of hazy days during June 1-5.
      Organic aerosols in the haze event were characterized by elevated concentrations
      of levoglucosan, high molecular weight (HMW) n-alkanes, and HMW fatty acids due
      to the emissions from field burning of wheat straw. In contrast, organic aerosols
      on nonhazy days were characterized by a predominance of fossil fuel combustion
      products. Levoglucosan (4030 n g m(-3)), n-alkanes (1520 ng m(-3)), fatty acids
      (2629 ng m(-3)), and PAHs (57 ng m(-3)) in the haze samples were 3-40 times more
      abundant than those in nonevent samples. Approximately 30-90% ofthe organics
      during the haze period can be attributed to wheat straw burning. Concentrations
      of particulate material (PM) mass, n-alkanes, and low molecular weight (LMW) PAHs
      showed a unimodal size distribution, peaking at 0.7-1.1 microm during the hazy
      days, and a bimodal distribution, peaking at 0.7-1.1 microm and 4.7-5.8 microm
      during nonhazy days. The geometric mean diameters (GMDs) of organic aerosols are
      larger in the fine mode (<2.1 microm) during the hazy days, suggesting aerosols
      emitted from the wheat straw burning are larger than those from fossil fuel
      combustion, and fine particle coagulation and organic compound repartitioning
      were enhanced.

PMID- 19764208
TI  - Investigation of surface properties of soil particles and model materials with
      contrasting hydrophobicity using atomic force microscopy.
AB  - Surface images and force measurements obtained using atomic force microscopy
      (AFM) were used to assess the hydrophobicity of particles from soils and model
      soil material (smooth glass and acid-washed sand (AWS) exposed to soil-derived
      humic acid (HA) or lecithin (LE)). Height and phase images, and phase
      distributions (from soil particles) show complex morphology and heterogeneously
      distributed organic matter. Forces at model surfaces indicate that, in air,
      reduction in adhesion corresponded with increased hydrophobicity, but in water,
      corresponded with a decrease (and serve to guide interpretation of data from
      natural particles). Adhesion forces on hydrophobic soil particles in water were
      larger than those for hydrophilic ones, but surface roughness and complexity may
      obscure any opposite trend for measurements in air. Combination of force
      measurements, applied forthe first time to soil particles, together with those on
      model surfaces, and independent assessments of hydrophobicity of corresponding
      single particle layers, indicate good, but not consistent qualitative agreement
      between hydophobicity at bulk and nanoscales. AFM is likely to facilitate
      detailed evaluation of soil particle surface hydrophobicity, which contributes to
      bulk wetting behavior of soils and other porous systems, including assessments of
      the potential for contributons to supehydrophobicity from surfaces at the micro-
      and nanoscales.

PMID- 19764209
TI  - Polyfluorinated compounds in the atmosphere of the Atlantic and Southern Oceans:
      evidence for a global distribution.
AB  - High volume air samples taken onboard several research vessels in the Atlantic
      Ocean, the Southern Ocean, and the Baltic Sea as well as at one land-based site
      close to Hamburg, Germany, in 2007 and 2008 were analyzed for per- and
      polyfluorinated organic compounds (PFCs). A set of neutral, volatile PFCs such as
      fluorotelomer alcohols (FTOH) or perfluoroalkyl sulfonamides and ionic
      nonvolatile PFCs like perfluorinated carboxylates (PFCA) and sulfonates (PFSA)
      were collected on PUF/XAD-2/PUF cartridges and glass fiber filters and determined
      using GC-MS and HPLC-MS/MS. PFCs were detected in all air samples, even in
      Antarctic regions, and occurred predominantly in the gas phase. Total gas-phase
      concentrations of ship-based samples ranged from 4.5 pg m(-3) in the Southern
      Ocean to 335 pg m(-3) in European source regions. Concentrations of 8:2 FTOH, the
      analyte that was usually observed in highest concentrations, were between 1.8 and
      130 pg m(-3). PFC concentrations decreased from continental regions toward marine
      regions and from Central Europe toward the Arctic and Antarctica. Southern
      hemispheric concentrations of individual PFCs were significantly lower than those
      of the northern hemisphere. On the basis of this data set, marine background PFC
      concentrations and atmospheric residence times were calculated. This study gives
      further evidence that volatile PFCs undergo atmospheric long-range transportto
      remote regions and may contribute to their contamination with persistent PFCA and
      PFSA.

PMID- 19764210
TI  - XANES speciation of P in environmental samples: an assessment of filter media for
      on-site wastewater treatment.
AB  - X-ray absorption near edge structure (XANES) spectroscopy is a useful technique
      for characterization of chemical species of phosphorus in complex environmental
      samples. To develop and evaluate bed filters as sustainable on-site wastewater
      treatment solutions, our objective in this study was to determine the chemical
      forms of accumulated phosphorus in a selection of promising filter materials:
      Filtralite P, Filtra P, Polonite, Absol, blast furnace slag, and wollastonite.
      Full-scale operational wastewater-treatment systems were sampled and in addition,
      filter samples collected from laboratory studies provided access to additional
      media and complementary samples. Phosphorus species were characterized using
      phosphorus K-edge XANES spectroscopy, complemented by X-ray powder diffraction
      (XRPD) and attenuated total reflectance Fourier-transform infrared spectroscopy
      (ATR-FTIR). No systematic differences could be seen in the results between
      laboratory- and full-scale samples. All six filter media contained significant
      amounts of crystalline calcium phosphates. Some samples also contained amorphous
      calcium phosphate (>60% of total P in Absol). In Filtralite P and blast furnace
      slag, more than 35% of the accumulated phosphorus was associated with Fe or Al.
      Both the power and shortcomings of XANES analysis for characterizing P species in
      these filter media are discussed.

PMID- 19764211
TI  - Time series of 129I and 127I speciation in precipitation from Denmark.
AB  - Environmental 129I mainly released from reprocessing plants at La Hague (France)
      and Sellafield (U.K.) provides a unique atmospheric and environmental tracer.
      This study deals with 129I and 127I speciation in precipitation collected in
      Denmarkduring 2001-2006 that indicates many newfindings. The concentrations of
      total 129I in precipitation vary from 0.28 to 5.63 x 10(9) atoms 129I L(-1) with
      an average of (2.34 +/- 1.43) x 10(9) atoms 129I L(-1), and the annual deposition
      flux of 129I is (1.25 +/- 0.30) x 10(12) atoms m(-2). Increased 129I levels in
      precipitation and 129I/ 127I ratio are attributed to the releases of 129I from
      the reprocessing plants at La Hague and Sellafield. Iodide is the major specie of
      129I, which accounts for 50-99% of total 129I. The concentrations of total 127I
      vary from 0.78 to 2.70 microg iodine L(-1) with an average of 1.63 +/- 0.47
      microg iodine L(-1), and annual deposition flux of 0.95 +/- 0.26 mg m(-2). Unlike
      129I, iodate is the major specie of 127I, which accounts for 43-93% of total
      127I. The 291I/ l27I atomic ratios for total iodine vary from 5.04 to 76.5 x 10(
      8) with an average of (30.1 +/- 16.8) x 10(-8). These values are 10 times lower
      for iodate with an average of (2.95 +/- 3.13) x 10(-8). Seasonal variations of
      129I/127 ml values and 129I concentrations are associated with highs in spring
      and lows in summer-autumn periods. Re-emission of 129 from the surface water of
      the English Channel, Irish Sea, North Sea, and Norwegian Sea, especially from the
      European continental coast areas, is evidently the major source of 129I in the
      precipitation, while stable 127I in the precipitation has multiple sources, i.e.,
      marine, as well as terrestrial emission. This work shows that data on speciation
      of iodine isotopes can provide thorough indications about the sources and
      geochemical cycle despite the complicated atmospheric chemistry of iodine.

PMID- 19764212
TI  - Assessment of nickel contamination in lakes using the phantom midge Chaoborus as
      a biomonitor.
AB  - Nickel (Ni) can be present in concentrations of concern in waters near mining and
      industrial sites. We tested species of the phantom midge Chaoborus as a
      biomonitor for this trace metal by collecting water and Chaoborus larvae from 15
      lakes located along a Ni gradient mainly in the vicinity of smelters located in
      Sudbury, ON, Canada. We measured pH, trace metals, major ions, as well as
      inorganic and organic carbon concentrations in lakewater for use in calculating
      ambient metal speciation using the Windermere Humic Aqueous Model (WHAM). Nickel
      concentrations in Chaoborus species varied widely among our study lakes and could
      be related to concentrations of the free Ni2+ ion in lakewater if competitive
      interactions with hydrogen ions (H+) were taken into account We verified this
      inhibitory effect in the laboratory by exposing Chaoborus punctipennis to
      constantfree Ni2+ ion concentrations at various H+ ion concentrations. As
      expected, larvae exposed to high concentrations of H+ ions accumulated less Ni.
      Overall, our results suggest that Chaoborus larvae would be an excellent
      biomonitor for Ni in lakewater and as such would be a useful component of risk
      assessment strategies designed to evaluate Ni exposure to aquatic organisms in
      lakes.

PMID- 19764213
TI  - Neutralization of calcite in mineral aerosols by acidic sullur species collected
      in China and Japan studied by ca K-edge X-ray absorption near-edge structure.
AB  - Calcium species in mineral aerosols collected simultaneously in Aksu (near the
      Taklimakan Desert), Qingdao (eastern China), and Tsukuba (Japan) during dust and
      nondust periods were determined using Ca K-edge X-ray absorption near-edge
      structure (XANES). From the fitting of XANES spectra, it was found that (i)
      calcite and gypsum were the main Ca species in the aerosol samples, and (ii) the
      gypsum fraction versus total Ca minerals [Gyp]/[Ca2+]t increased progressively in
      the order Aksu < Qingdao < Tsukuba. Surface-sensitive XANES in the conversion
      electron yield mode (CEY) showed that the gypsum is formed selectively at the
      surface of mineral aerosols for all the samples except for that taken in Aksu
      during the dust period. The decrease of the [Gyp]/[Ca2+]t ratio with an increase
      in particle size showed that the neutralization effect proceeds from the particle
      surface. For the Aksu sample in the dust period, however, (i) the [Gyp]/[Ca2+]t
      ratios obtained by XANES measured in the fluorescence (FL; regarded as bulk
      analysis) and CEY modes were similar and (ii) size dependence was not found,
      showing that neutralization is not important for the sample because of the large
      supply of mineral aerosol with little neutralization effect in Aksu. It was also
      found that the pH of the aerosol and the ratio of (NH4)2SO4 to gypsum were
      positively and negatively correlated with the Ca (or calcite) content,
      respectively. The speciation of Ca by XANES revealed the neutralization processes
      of acidic sulfur species by calcite during the long-range transport of mineral
      aerosols.

PMID- 19764214
TI  - Effect of Mn(II) on the structure and reactivity of biogenic uraninite.
AB  - The efficacy of a site remediation strategy involving the stimulaton of microbial
      U(VI) reduction hinges in part upon the long-term stability of the product,
      biogenic uraninite, toward environmental oxidants. Geological sedimentary
      uraninites (nominal formula UO2) reportedly contain abundant cation impurities
      that enhance their resistance to oxidation. By analogy, incorporation of common
      groundwater solutes into biogenic uraninite could also impart stability-enhancing
      properties. Mn(II) is a common groundwater cation, which has a favorable ionic
      radiusfor substitution reactions. The structure and reactivity of Mn(II)-reacted
      biogenic uraninite are investigated in this study. Up to 4.4 weight percent
      Mn(II) was found to be structurally bound in biogenic uraninite. This Mn(II)
      incorporation was associated with decreasing uraninite particle size and
      structural order. Importantly, the equilibrium solubility of Mn-reacted uraninite
      was halved relative to unreacted uraninite, demonstrating changes in
      thermodynamic properties, while the dissolution rate was up to 38-fold lower than
      that of unreacted biogenic uraninite. We conclude that structuralincorporation of
      Mn(II) into uraninite has an important stabilizing effect leading to the
      prediction that other groundwater solutes may similarly stabilize biogenic
      uraninite.

PMID- 19764215
TI  - Does iron cycling trigger generation of acidity in groundwaters of Western
      Australia?
AB  - In large areas of Western Australia, acidic groundwaters occur with pH values
      distinctly lower than 3, generation of which has been attributed to the oxidation
      of Fe(II). Incubation experiments performed with sediments from playas receiving
      acid groundwater demonstrated occurrence of reductive dissolution of ferric iron
      minerals at rates [670 nmol (g reactive iron)(-1) h(-1)] similar to those
      observed in sediments of acidic mining lakes (AML), indicating thatthe pH was
      established through an acidity-driven iron cycle in analogy to processes
      occurring in AML systems. The low pH values observed in acidic groundwaters and
      AML, however, can only be achieved if the anion corresponding to Fe(III) is that
      of a strong acid. In AML, sulfate is derived from pyrite oxidation. Because this
      process is reported not to occur in the acidic groundwater systems of Western
      Australia, we have derived a conceptual model according to which sulfate is
      generated upon reaction of weathering-derived alkalinity with gypsum to form
      calcite, which is abundant in these areas. The model proposes that part of the
      alkalinity generated during weathering is stared as calcite in the landscape,
      which leads to spatial separation of acidity and alkalinity.

PMID- 19764216
TI  - Effect of environmental conditions on sulfate reduction with methane as electron
      donor by an Eckemforde Bay enrichment.
AB  - Sulfate reduction (SR) coupled to anaerobic oxidation of methane (AOM) is
      meditated by marine microorganisms and forms an important process in the global
      sulfur and carbon cycle. In this research, the possibility to use this process
      for the removal and recovery of sulfur and metal compounds from waste streams was
      investigated. A membrane bioreactor was used to enrich for a community of methane
      oxidizing sulfate-reducing microorganisms from Eckernforde Bay sediment The AOM
      and SR rate of the obtained enrichment were 1.0 mmol gvss(-1) d(-1). The
      operational window and optimal environmental conditions for SR with methane as
      electron donor were assessed. The optimum pH, salinity, and temperature were 7.5,
      30% per hundred and 20 degrees C, respectively. The enrichment had a good
      affinity for sulfate (Km < 0.5 mM) and a low affinity for methane (Kn > 0.075
      MPa). A0M coupled to SR was completely inhibited at 2.4 (L0.1) mM sulfide. AOM
      occurred with sulfate, thiosulfate, and sulfite as electron accepters. Sulfate
      reduction with methane as electron donor can be applied for the removal of
      sulfate or for the production of sulfide,for metal precipitation. However, the
      low optimal temperature and the high salt requirement limit the operational
      window of the process.

PMID- 19764217
TI  - Kinetics of uranium(VI) desorption from contaminated sediments: effect of
      geochemical conditions and model evaluation.
AB  - Stirred-flow cell experiments were performed to investigate the kinetics of
      uranyl [U(VI)] desorption from a contaminated sedimentcollected from the Hanford
      300 Area at the U.S. Department of Energy Hanford Site, Washington. Three
      influent solutions of variable pH, Ca and carbonate concentrations that affected
      U(VI) aqueous and surface speciation were used under dynamic flow conditions to
      evaluate the effect of geochemical conditions on the rate of U(Vl) desorption.
      The measured rate of U(VI) desorption varied with solution chemical composition
      that evolved as a result of thermodynamic and kinetic interactions between the
      solutions and sediment The solution chemical composition that led to a larger
      disequilibrium between adsorbed U(VI) and equilibrium adsorption state yielded a
      faster desorption rate. The experimental results were used to evaluate a
      multirate, surface complexation model (SCM) that has been proposed to describe
      U(VI) desorption kinetics in the Hanford sedimentthat contained complex adsorbed
      U(VI) in mass transfer limited domains (Lui et al. Water Resour. Res. 2008, 44,
      W08413). The model was modified and supplemented by including multirate, ion
      exchange reactions to describe the geochemical interactions between the solutions
      and sediment With the same setof model parameters, the modified model reasonably
      well described the evolution of major ions and the rates of U(VI) desorption
      under variable geochemical and flow conditions, implying that the multirate SCM
      is an effective way to describe U(VI) desorption kinetics in subsurface
      sediments.

PMID- 19764218
TI  - Neptuniumnn(V) sorption and diffusion in opalinus clay.
AB  - The sorption and diffusion behavior of 8 x 10(-6) M Np(V) in Opalinus Clay (OPA)
      with synthetic pore water (pH 7.6) as mobile phase was studied under ambient
      conditions by batch and diffusion experiments, respectively. The Kd value
      determined by batch experiments with OPA suspensions is equal to 0.025 +/- 0.005
      m3/kg. The diffusion-accessible porosity epsilon of intact OPA as determined by
      through- and out-diffusion experiments with tritiated water (HTO) is equal to
      0.15 +/- 0.01. The diffusion coefficient De and the rock capacity factor alpha of
      22Na+ in OPA were measured by through-, out-, and in-diffusion experiments and
      asserted the reliability of these diffusion techniques. For the diffusion of
      Np(V) in synthetic pore water, the capillary method gave Dw = (6.0 +/- 1.0) x 10(
      10) m/s. Due to the strong sorption of Np(V) on CPA, the diffusion of Np(V) was
      investigated bythe in-diffusiontechnique.The diffusion parameters for Np(V) in
      OPA are De = (6.9 +/- 1.1) x 10(-12) m2/s and alpha = 243 +/- 4. This corresponds
      to Kd = 0.10 +/- 0.01 m3/kg for the sorption of Np(V) in intact OPA.

PMID- 19764219
TI  - Evidence for regulation of monomethyl mercury by nitrate in a seasonally
      stratified, eutrophic lake.
AB  - The accumulation of monomethyl mercury (CH3Hg+) in aquatic ecosystems is a redox
      sensitive process that is accelerated under sulfate-reducing conditions. While
      nitrate (NO3-) reduction is energetically favored over sulfate reduction, the
      influence of NO3 on the accumulation of CH3Hg+ has not been reported in the
      literature. We examined temporal and vertical patterns in redox constituents and
      CH3Hg+ concentrations in the hypolimnion of a dimictic lake, Onondaga Lake, prior
      to and following increases in NO3- inputs. Detailed water-column profiles and a
      long-term record revealed marked decreases in the accumulation of CH3Hg+ in the
      anoxic hypolimnion coinciding with long-term decreases in the deposition of
      organic matter coupled with recent increases in NO3-concentrations. CH3Hg+
      concentrations in the hypolimnion were substantially abated when No3 was present
      above the sediment-water interface. A decrease in the peak hypolimnetic mass of
      CH3Hg+ and shortening of the period of elevated CH3Hg+ concentrations resulted in
      more than a 50% decline in the accumulated CH3Hg+. N03- regulation of CH3Hg+
      accumulation may be a widespread phenomenon in oxygen-limited freshwater and
      terrestrial environments, and could have an important notpreviously recognized,
      effect on the biogeochemistry of mercury.

PMID- 19764220
TI  - Assessment of peracetic acid disinfected effluents by microbiotests.
AB  - Bioassays were performed by commercially available kits on peracetic acid (PAA)
      solutions, at different concentrations, and on secondary effluents (from two
      different wastewater treatment plants) after disinfection at bench-scale,
      considering both samples containing residual active PAA and the same samples
      where residual PAA was quenched. Four indicator organisms were used: Vibrio
      fischeri, Thamnocephalus platyurus, Daphnia magna, and Selenastrum capricornutum.
      The experiments lead to conclude that Thamnocephalus platyurus is a very
      sensitive organism, probably not adequate to perform a reliable toxicity
      assessment of effluents for monitoring purposes. The presence of specific organic
      compounds deriving from human metabolism and urban pollution, even at very low
      concentrations, can affect the results of bioassays, especially those performed
      on Vibrio fischeri. PAA is toxic for bacteria and crustaceans even at
      concentrations lower than the ones commonly used in wastewater disinfection (2-5
      mg/L), while its effect on algae is smaller. The toxic effect on bacteria was
      expected, as PAA is used for disinfection, but its possible influence on
      biological processes in the receiving aquatic environment should be considered.
      Toxicity on crustaceans would confirm the fact that discharging disinfected
      effluents could raise some environmental problems.

PMID- 19764221
TI  - Arsenite and ferrous iron oxidation linked to chemolithotrophic denitrification
      for the immobilization of arsenic in anoxic environments.
AB  - The objective of this study was to explore a bioremediation strategy based on
      injecting NO3- to support the anoxic oxidation of ferrous iron (Fe(II)) and
      arsenite (As(II)) in the subsurface as a means to immobilize As in the form of
      arsenate (As(V)) adsorbed onto biogenic ferric (Fe(III)) (hydr)oxides. Continuous
      flow sand filled columns were used to simulate a natural anaerobic groundwater
      and sediment system with co-occurring As(III) and Fe(II) in the presence (column
      SF1) or absence (column SF2) of nitrate, respectively. During operation for 250
      days, the average influent arsenic concentration of 567 microg L(-1) was reduced
      to 10.6 (+/-9.6) microg L(-1) in the effluent of column SF1. The cumulative
      removal of Fe(II) and As(II) in SF1 was 6.5 to 10-fold higher than that in SF2
      Extraction and measurement of the mass of iron and arsenic immobilized on the
      sand packing of the columns were close to the iron and arsenic removed from the
      aqueous phase during column operation. The dominant speciation of the immobilized
      iron and arsenic was Fe(III) and As(V) in SF1, compared with Fe(II) and As(III)
      in SF2. The speciation was confirmed by X-ray diffraction (XRD) and X-ray
      photoelectron spectroscopy (XPS). The results indicate that microbial oxidation
      of As(III) and Fe(II) linked to denitrification resulted in the enhanced
      immobilization of aqueous arsenic in anaerobic environments by forming Fe(III)
      (hydr)oxide coated sands with adsorbed As(V).

PMID- 19764222
TI  - Formation of iron nanoparticles and increase in iron reactivity in mineral dust
      during simulated cloud processing.
AB  - The formation of iron (Fe) nanoperticles and increase in Fe reactivity in mineral
      dust during simulated cloud processing was investigated using high-resolution
      microscopy and chemical extraction methods. Cloud processing of dust was
      experimentally simulated via an alternation of acidic (pH 2) and circumneutral
      conditions (pH 5-6) over periods of 24 h each on presieved (<20 microm) Saharan
      soil and goethite suspensions. Microscopic analyses of the processed soil and
      goethite samples reveal the neo-formation of Fe-rich nanoparticle aggregates,
      which were not found initially. Similar Fe-rich nanoparticles were also observed
      in wet-deposited Saharen dusts from the western Mediterranean but not in dry
      deposited dust from the eastern Mediterranean. Sequential Fe extraction of the
      soil samples indicated an increase in the proportion of chemically reactive Fe
      extractable by an ascorbate solution after simulated cloud processing. In
      addition, the sequential extractions on the Mediterranean dust samples revealed a
      higher content of reactive Fe in the wet-deposited dust compared to that of the
      dry-deposited dust These results suggestthat large variations of pH commonly
      reported in aerosol and cloud waters can trigger neo-formation of nanosize Fe
      particles and an increase in Fe reactivity in the dust

PMID- 19764223
TI  - Colloidal properties of aqueous fullerenes: isoelectric points and aggregation
      kinetics of C60 and C60 derivatives.
AB  - Aqueous colloidal suspensions of C60 (aqu/C60) and the C60 derivatives PCBM
      ([6,6]-phenyl C61-butyric acid methyl ester) and the corresponding butyl and
      octyl esters, PCBB and PCBO (aqu/PCB-R, where R is an alkyl group), were produced
      by stirring in double deionized water for 5 months. Kinetically stable fullerene
      aggregates were formed using this procedure that ranged in intensity-averaged
      hydrodynamic diameter (Dh) from 193 +/- 2 nm (95% C.L.) for aqu/C60 to 259 +/- 6
      nm for aqu/PCBO. Measured zeta potentials (zeta) were < -50 mV, and the
      isoelectric points (p) were < 1.0 for all of the aqu/fullerenes. Time-resolved
      dynamic light scattering (TRDLS) was used to measure aqu/fullerene Dh change with
      time and as a function of background solution ionic strength. The critical
      coagulation concentration (CCC) values for the aqu/PCB-R fullerenes were
      significantly higher than that of aqu/C60, indicating that the phenyl alkyl ester
      moieties of the equ/PCB-R fullerenes were impeding the aggregation process.

PMID- 19764224
TI  - Photochemical and antimicrobial properties of novel C60 derivatives in aqueous
      systems.
AB  - Four novel hexakis C60 derivatives with varying functionalities were synthesized,
      and their photochemical properties and photodynamic disinfection efficiencies
      were quantitatively evaluated. All these C. derivatives generated O2 more
      efficiently than commercial multihydroxylated C60 (fullerol), as assessed by
      furfuryl alcohol consumption and electron paramagnetic resonance analysis.
      Despite significant agglomeration/aggregation in the aqueous phase to micrometer
      sized particles, nanosecond laser flash photolysis showed that the lifetime of
      triplet state (a key intermediate for energy transfer responsible for (1)O2
      production) was comparable to reported values for pristine C. in organic phase.
      As a result of facile (1)O2 production, the Co derivatives efficiently
      inactivated Escherichie coli and MS-2 bacteriophage. Cationic aminofullerene
      hexakis, which likely exerted electrostatic attraction, exhibited exceptionally
      rapid virus inactivation even compared to commercial nano-TiO2 photocatalyst
      These unique photodynamic, hydrophilic and cationic properties may be
      instrumental for the development of next generation photocatalysts for
      disinfection applications. The high ROS (reactive oxygen species) production
      activity and associated cytotoxicity are concerns for potential releases of
      functionalized Ca to the environment, and require careful assessment apart from
      other forms of C60 (e.g., nC60) that have been widely studied as model
      nanomaterials but behave differently.

PMID- 19764225
TI  - Identification of retinoic acid receptor agonists in sewage treatment plants.
AB  - Retinoic acid receptor (RAR) agonists are speculated to be one possible cause for
      the widely observed frog deformities in North America, although little is known
      about the specific RAR agonists in aquatic environments. We identified the
      specific RAR egonists in sewage treatment plants (STPs) and receiving rivers
      using an RAR yeast two-hybrid bioassay. Water samples were extracted by solid
      phase extract cartridges, which were successively eluted by hexane, ethyl
      acetate, and methanol for bioassay. Among the three fractions, the ethyl acetate
      fraction showed the highest RAR agonistic activities. The bioassay-derived
      activity, expressed as all-trans-retinoic acid (all-transRA) equivalents (ATRA
      EQ) were 10.9 +/- 2.2 and 1.7 +/- 1.0 ng/L in the STP influents and effluents,
      respectively, while the ATRA-EQs were as high as 7.1 and 8.3 ng/L in the two
      rivers receiving STP effluents. Following a two-step fractionation using high
      performance liquid chromatography and ultra-performance liquid chromatography
      (UPLC) directed by the bioassay, two bioactive fractions were obtained from
      Gaobeidian STP influent and all-trans-4-oxo-RA (4.7-10.4 ng/L in influents, < 0.2
      0.9 ng/L in effluents) and 13-cis-4-oxo-RA (2.3-7.1 ng/L in influents, < 0.4-1.1
      ng/L in effluents) were identified in these fractions with UPLC-MS/MS. The EC50
      for all-trans-4-oxo-RA or 13-cis-4-oxo-RA relative to that of all-trans-RA in
      exhibiting RARalpha agonistic activity was calculated to be 3.87 and 0.46,
      respectively.

PMID- 19764226
TI  - Degradability of an acrylate-linked, fluorotelomer polymer in soil.
AB  - Fluorotelomer polymers are used in a broad array of products in modern societies
      worldwide and, if they degrade at significant rates, potentially are a
      significant source of perfluorooctanoic acid (PFOA) and related compounds to the
      environment To evaluate this possibility, we incubated an acrylate-linked
      fluorotelomer polymer in soil microcosms and monitored the microcosms for
      possible fluorotelomer (FT) and perfluorinated-compound (PFC) degradation
      products using GC/MS and LC/MS/MS. This polymer scavenged FTs and PFCs
      aggressively necessitating development of a multistep extraction using two
      solvents. Aged microcosms accumulated more FTs and PFCs than were present in the
      fresh polymer indicating polymer degradation with a half-life of about 870-1400
      years for our coarse-grained test polymer. Modeling indicates that more-finely
      grained polymers in soils might have half-lives of about 10-17 years assuming
      degradation is surface-mediated. In our polymer-soil microcosms, PFOA evidently
      was lost with a half-life as short as 130 days, possibly by polymer-catalyzed
      degradation. These results suggest that fluoratelomer-polymer degradation is a
      significant source of PFOA and other fluorinated compounds to the environment.

PMID- 19764227
TI  - The inhibition of Pb(IV) oxide formation in chlorinated water by orthophosphate.
AB  - Historically, understanding lead solubility and its control in drinking water has
      been based on Pb(II) chemistry. Unfortunately, there is very little information
      available regarding the nature of Pb(IV) oxides in finished drinking water and
      water distribution systems, and the conditions under which they persist. The
      objective of this research was to explore the impact of orthophosphate on the
      realistic pathways that lead to the formation of Pb(IV) oxides in chlorinated
      water. The results of XRD and XANES analysis showed that, in the absence of
      orthophosphate (DIC = 10 mg C/L, 24 degrees C, pH 7.75-8.1, 3 mg Cl2/L goal),
      Pb(IV) oxides formed with time following a transformation from the Pb(II) mineral
      hydrocerussite. Under the same experimental conditions, orthophosphate dosing
      inhibited the formation of Pb(IV) oxides. The Pb(II) mineral hydroxypyromorphite,
      Pb5(PO4)3OH, was the only mineral phase identified during the entire study of
      over 600 days, although the presence of some chloropyromorphite, Pb5(PO4)3Cl,
      could not be ruled out The conclusions were further supported by SEM, TEM, and
      XANES analysis of lead colloids, and lead precipitation experiments conducted in
      the absence of free chlorine. The findings provide an important explanation for
      the absence of Pb(IV) oxides in some water systems that have used, or currently
      use, orthophosphate for corrosion control when otherwise, based on disinfection
      practices and water quality, its presence would be anticipated, as well as why
      the conversion from free chlorine to chloramines was not observed to increase
      lead release.

PMID- 19764228
TI  - Cation binding of antimicrobial sulfathiazole to leonardite humic acid.
AB  - Sorption of sulfathiazole (STA) and three structural analogs to Leonardite humic
      acid (LHA) was investigated in single- and binary-solute systems to elucidate the
      sorption mechanism of sulfonamides to soil organic matter (SOM). Cation binding
      of STA+ to anionic sites A- in LHA governed sorption up to circumneutral pH,
      based on the following findings: (i) From pH 7.7 to 3.3, the increase in extent
      and nonlinearity (i.e., concentration dependence) of STA sorption paralleled the
      increase in STA+. (ii) From pH 3.3 to 1.7, sorption decreased and nonlinearity
      increased, consistent with strong competition of STA+ and H+ for A-. (iii)
      Replacement of the protonable aniline group in STA by an apolar methylbenzene
      group resulted in much weaker, linear, and pH-independent sorption. (iv) Only
      analogs with aniline moieties displaced STA from LHA in binary-solute systems.
      Displacement occurred up to pH 5.4, at which <1% of STA in solution was cationic.
      (v) STA sorption was well-described (R2 = 0.98) by the NICA-Donnan cation-binding
      model, yielding high median affinities for STA+ to carboxylic and phenolic A-
      (log K(STA+,1) = 3.25 +/- 0.08 log (L mol(-1)) and log K(STA+,2) = 8.76 +/- 0.11
      log (L mol(-1)), respectively). High affinity cation binding explains sorption of
      polar sulfonamides in agricultural soils and the strong dependence of sorption on
      SOM content and pH.

PMID- 19764229
TI  - Mechanisms of bacteriophage inactivation via singlet oxygen generation in UV
      illuminated fullerol suspensions.
AB  - Nonenveloped viruses are shown to be inactivated by singlet oxygen ((1)O2)
      produced in UVA photosensitized aqueous suspensions of a polyhydroxylated
      fullerene (C60(OH)22-24; fullerol, 40 microM). Experiments were performed with
      MS2, a ssRNA bacteriophage, as well as two dsDNA phages: PRD1, which has an
      internal lipid membrane, and T7, which entirely lacks lipids. MS2 was highly
      susceptible to inactivation, having a rate constant of 0.034 min(-1) with UVA
      alone, which increased to 0.102 min(-1) with photoactivated fullerol. PRD1 and T7
      were not susceptible to UVA alone but were photoinactivated by fullerol with rate
      constants of 0.026 and 0.035 min(-1), respectively. The role of 1(O)2 was
      demonstrated by three independent observations: (i) viruses that were insensitive
      to UVA alone were photoinactivated by rose bengal in the absence of fullerol,
      (ii) beta-carotene reduced (but did not eliminate) photoinactivation rates, and
      (iii) singlet oxygen sensor green fluorescence spectroscopy directly detected
      (1)O2 in UVA illuminated fullerol suspensions. Qualitative evidence is also
      presented that fullerol aggregates were closely associated with viruses allowing
      efficient transfer of 1(O)2 to their capsids. Fourier transform infrared
      spectroscopy revealed significant oxidative modifications to capsid proteins but
      comparatively minor changes to the DNA and (phospho)lipids. Sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) suggested (1)O2 induced
      crosslinking of proteins. Hence, phage inactivation by photoactivated fullerol
      nanoparticles appears to be caused by cross-linking of capsid protein secondary
      structures by exogenous (1)O2 and consequentimpairmentof their ability to bind to
      surface receptors of their bacterial hosts (loss of infectivity) rather than by
      direct reactions with fullerol.

PMID- 19764230
TI  - Influence of operating parameters on the biodegradation of steroid estrogens and
      nonylphenolic compounds during biological wastewater treatment processes.
AB  - This study investigated operational factors influencing the removal of steroid
      estrogens and nonylphenolic compounds in two sewage treatment works, one a
      nitrifying/denitrifying activated sludge plant and the other a
      nitrifying/denitrifying activated sludge plant with phosphorus removal. Removal
      efficiencies of >90% for steroid estrogens and for longer chain nonylphenol
      ethoxylates (NP4-12EO) were observed at both works, which had equal sludge ages
      of 13 days. However, the biological activity in terms of milligrams of estrogen
      removed per day per tonne of biomass was found to be 50-60% more efficient in the
      nitrifying/denitrifying activated sludge works compared to the works which
      additionallyincorporated phosphorusremoval. A temperature reduction of 6 degrees
      C had no impact on the removal of free estrogens, but removal of the conjugated
      estrone-3-sulfate was reduced by 20%. The apparent biomass sorption (LogKp)
      values were greater in the nitrifying/denitrifying works than those in the
      nitrifying/denitrifying works with phosphorus removal for both steroid estrogens
      and honylphenolic compounds possibly indicating a different cell surface
      structure and therefore microbial population. The difference in biological
      activity (mg tonne(-1) d(-1)) identified in this study, of up to seven times,
      suggests thatthere is the potential for enhancing the removal of estrogens and
      nonylphenols if more detailed knowledge of the factors responsible for these
      differences can be identified and maximized, thus potentially improving the
      quality of receiving waters.

PMID- 19764231
TI  - Quantum chemical study of arsenic (III, V) adsorption on Mn-oxides: implications
      for arsenic(III) oxidation.
AB  - Density functional theory (DFT) calculations were used to investigate As(V) and
      As(III) surface complex structures and reaction energies on both Mn(III) and
      Mn(IV) sites in an attempt to better understand As(III) oxidation bybirnessite, a
      layered Mn-dioxide mineral. Edge-sharing dioctahedral Mn(III) and Mn(IV) clusters
      with different combinations of surface functional groups (>MnOH and >MnOH2) were
      employed to mimic pH variability. Results show that As(V) adsorption was more
      thermodynamically favorable than As(III) adsorption on both Mn(III) and Mn(IV)
      surface sites under simulated acidic pH conditions. Therefore, we propose that
      As(V) adsorption inhibits As(III) oxidation by blocking adsorption sites. Under
      simulated acidic pH conditions, Mn(IV) sites exhibited stronger adsorption
      affinity than Mn(III) sites for both As(III) and As(V). Overall, we hypothesize
      that Mn(III) sites are less reactive in terms of As(III) oxidation due to their
      lower affinity for As(III) adsorption, higher potential to be blocked by As(V)
      complexes, and slower electron transfer rates with adsorbed As(III). Results from
      this study offer an explanation regarding the experimental observations of
      Mn(III) accumulation on birnessite and the long residence time of As(III)
      adsorption complexes on manganite (r-MnOOH) during As(III) oxidation.

PMID- 19764232
TI  - Determining the probability of arsenic in groundwater using a parsimonious model.
AB  - Spatial distributions of groundwater quality are commonly heterogeneous, varying
      with depths and locations, which is important in assessing the health and
      ecological risks. Owing to time and cost constraints, it is not practical or
      economical to measure arsenic everywhere. A predictive model is necessary to
      estimate the distribution of a specific pollutant in groundwater. This study
      developed a logistic regression (LR) model to predict the residential well water
      quality in the Lanyang plain. Six hydrochemical parameters, pH, NO3- -N, NO2- -N,
      NH+ -N, Fe, and Mn, and a regional variable (binary type) were used to evaluate
      the probability of arsenic concentrations exceeding 10 microg/L in groundwater.
      The developed parsimonious LR model indicates that four parameters in the Lanyang
      plain aquifer, (pH, NH4+, Fe(aq), and a component to account for regional
      heterogeneity) can accurately predict probability of arsenic concentration > or
      =1 microg/Lin groundwater. These parameters provide an explanation for release of
      arsenic by reductive dissolution of As-rich FeOOH in NH4+ containing groundwater.
      A comparison of LR and indicator kriging (IK) show similar results in modeling
      the distributions of arsenic. LR can be applied to assess the probability of
      groundwater arsenic at sampled sites without arsenic concentration data apriori.
      However, arsenic sampling is still needed and required in arsenic-assessment
      stages in other areas, and the need for long-term monitoring and maintenance is
      not precluded.

PMID- 19764233
TI  - Comparison of source apportionment and sensitivity analysis in a particulate
      matter air duality model.
AB  - Two efficient methods to study relationships between particulate matter (PM)
      concentrations and emission sources are compared in the three-dimensional
      comprehensive air quality model with extensions (CAMx). Particulate source
      apportionment technology (PSAT) is a tagged species method that apportions
      concentrations of PM components to their respective primary precursors, e.g.,
      sulfate is apportioned to SOx, nitrate to NOx, etc. The decoupled direct method
      (DDM) calculates first-order sensitivities of PM concentrations to model inputs.
      Both tools were applied to two month long (February and July) PM modeling
      episodes and evaluated against changes in PM concentrations due to various
      emission reductions. The results show that source contributions calculated by
      PSAT start to deviate from the actual model responses as indirect effects from
      limiting reactants or nonprimary precursor emissions become important The DDM
      first-order sensitivity is useful for determining source contributions only if
      the model response to input changes is reasonably linear. For secondary inorganic
      PM, the response is linear for emission reductions of 20% in all cases considered
      and reasonably linear for reductions of 100% inthe case of on-road mobile
      sources. The model response for secondary organic aerosols and primary PM remains
      nearly linear to 100% reductions in anthropogenic emissions.

PMID- 19764234
TI  - Development and exploration of an organic contaminant fate model using poly
      parameter linear free energy relationships.
AB  - Octanol-based partitioning relationships, referred to as single-parameter linear
      free energy relationships (SP-LFERS), are often criticized for their limited
      applicability to polar organic substances. Therefore, SP-LFERS describing
      environmental phase partitioning in CoZMo-POP2, a dynamic multimedia chemical
      fate model, are replaced with poly-parameter linear free energy relationships (PP
      LFERS) which describe temperature-dependent partitioning as the linear sum of
      various specific and nonspecific molecular interactions. A data set of chemicals
      with available solute descriptors, which quantify these molecular interactions,
      is compiled from the literature and, together with a data set of hypothetical
      chemicals, used to investigate the differences in the predictions of SP-LFER- and
      PP-LFER-based model in relative and absolute terms for three different emission
      scenarios. Model outputs are manipulated to allow the results to be displayed as
      a function of log K(AW) and log K(OA). Whereas the primary environmental fate is
      similar in both models, differences arise mostly in the environmental phases
      which contain only a small fraction of chemical. Larger differences in model
      results occur either because a difference in the predicted partitioning between
      water and organic matter affects the extent of soil-water runoff, or because
      differences in gas-particle partitioning affectthe relative deposition to aqueous
      and forested surfaces. The two models showed smaller differences for degradable
      chemicals than for chemicals assumed to be perfectly persistent Overall, however,
      the absolute differences between the model results are relatively small in
      comparison to the precision generally associated with model parametrization.
      Accordingly, we suggest that the quality of the available chemical input
      parameters should decide whether a PP-LFER model is preferable over a SP-LFER
      model. The PP-LFER model is further used to evaluate the effects of various
      molecular interactions on chemical fate, and the solute descriptor associated
      with van der Waals dispersive interactions is found to have the most pronounced
      effect on the environmental distribution of chemicals.

PMID- 19764235
TI  - A probabilistic assessment of the chemical and radiological risks of chronic
      exposure to uranium in freshwater ecosystems.
AB  - Uranium (U) presents a unique challenge for ecological risk assessments (ERA)
      because it induces both chemical and radiological toxicity, and the relative
      importance of these two toxicities differs among the various U source terms
      (i.e., natural, enriched, depleted). We present a method for the conversion
      between chemical concentrations microg L(-1)) and radiological dose rates
      (microGy h(-1)) for a defined set of reference organisms, and apply this
      conversion method to previously derived chemical and radiological benchmarks to
      determine the extent to which these benchmarks ensure radiological and chemical
      protection, respectively, for U in freshwater ecosystems. Results show that the
      percentage of species radiologically protected by the chemical benchmark
      decreases with increasing degrees of U enrichment and with increasing periods of
      radioactive decay. In contrast, the freshwater ecosystem is almost never
      chemically protected by the radiological benchmark, regardless of the source term
      or decay period considered, confirming that the risks to the environment from
      uranium's chemical toxicity generally outweigh those of its radiological
      toxicity. These results are relevant to developing water quality criteria that
      protect freshwater ecosystems from the various risks associated with the nuclear
      applications of U exploitation, and highlight the need for (1) further research
      on the speciation, bioavailability, and toxicity of U-series radionuclides under
      different environmental conditions, and (2) the adoption of both chemical and
      radiological benchmarks for coherent ERAs to be conducted in U-contaminated
      freshwater ecosystems.

PMID- 19764236
TI  - Rapid detection of Naegleria fowleri in water distribution pipeline biofilms and
      drinking water samples.
AB  - Rapid detection of pathogenic Naegleria fowler in water distribution networks is
      critical for water utilities. Current detection methods rely on sampling drinking
      water followed by culturing and molecular identification of purified strains.
      This culture-based method takes an extended amount of time (days), detects both
      nonpathogenic and pathogenic species, and does not account for N. fowleri cells
      associated with pipe wall biofilms. In this study, a total DNA extraction
      technique coupled with a real-time PCR method using primers specific for N.
      fowleri was developed and validated. The method readily detected N. fowleri
      without preculturing with the lowest detection limit for N. fowleri cells spiked
      in biofilm being one cell (66% detection rate) and five cells (100% detection
      rate). For drinking water, the detection limit was five cells (66% detection
      rate) and 10 cells (100% detection rate). By comparison, culture-based methods
      were less sensitive for detection of cells spiked into both biofilm (66%
      detection for <10 cells) and drinking water (0% detection for <10 cells). In
      mixed cultures of N. fowleri and nonpathogenic Naegleria, the method identified
      N. fowleri in 100% of all replicates, whereastests with the current consensus
      primers detected N. fowleri in only 5% of all replicates. Application of the new
      method to drinking water and pipe wall biofilm samples obtained from a
      distribution network enabled the detection of N. fowleri in under 6 h, versus 3+
      daysforthe culture based method. Further, comparison of the real-time PCR data
      from the field samples and the standard curves enabled an approximation of N.
      fowleri cells in the biofilm and drinking water. The use of such a method will
      further aid water utilities in detecting and managing the persistence of N.
      fowleri in water distribution networks.

PMID- 19764237
TI  - Determination of the aerosol yield of isoprene in the presence of an organic seed
      with carbon isotope analysis.
AB  - We examined a new method to determine the aerosol yield of precursors of
      secondary organic aerosols in the presence of organic seed particles. To
      distinguish between the oxidation products of the compound in question and the
      organic seed, the compound was labeled with stable isotopes and aerosol samples
      were analyzed by isotope ratio mass spectrometry (IRMS). 13C labeled isoprene was
      obtained from isoprene emitting plants that were exposed to (13)CO2. The aerosol
      yield of isoprene was determined from the 13C/12C ratio measured in the aerosol.
      Measurements at organic aerosol mass concentrations as low as 10 microg m(-3)
      were performed. Three different methods of aerosolsampling procedureswere
      evaluated: impactor, filter, and electrostatic deposition. The excess-% 13C
      measured by the three sampling methods agreed well. The aerosol yield of isoprene
      derived from these measurements showed a strong dependence on further oxidation
      of first-generation products and is within the range of reported yield values (1
      5%) obtained so far from pure isoprene experiments.

PMID- 19764238
TI  - Field-based detection and monitoring of uranium in contaminated groundwater using
      two immunosensors.
AB  - Field-based monitoring of environmental contaminants has long been a need for
      environmental scientists. Described herein are two kinetic exclusion-based
      immunosensors, a field portable sensor (FPS) and an inline senor, that were
      deployed at the Integrated Field Research Challenge Site of the U.S. Department
      of Energy in Rifle, CO. Both sensors utilized a monoclonal antibody that binds to
      a U(VI)-dicarboxyphenanthroline complex (DCPI in a kinetic exclusion immunoassay
      format These sensors were able to monitor changes of uranium in groundwater
      samples from approximately 1 microM to below the regulated drinking water limit
      of 126 nM (30 ppb). The FPS is a battery-operated sensor platform that can
      determine the uranium level in a single sample in 5-10 min, if the instrument has
      been previously calibrated with standards. The average minimum detection level
      (MDL) in this assay was 0.33 nM (79 ppt), and the MDL in the sample (based on a
      1:200-1:400 dilution) was 66-132 nM (15.7-31.4 ppb). The inline sensor, while
      requiring a grounded power source, has the ability to autonomously analyze
      multiple samples in a single experiment The average MDL in this assay was 0.12 nM
      (29 ppt), and the MDL in the samples (based on 1:200 or 1:400 dilutions) was 24
      48 nM (5.7-11.4 ppb). Both sensor platforms showed an acceptable level of
      agreement (9 = 0.94 and 0.76, for the inline and FPS, respectively) with
      conventional methods for uranium quantification.

PMID- 19764239
TI  - Measurements of hygroscopicity and volatility of atmospheric ultrafine particles
      during ultrafine particle formation events at urban, industrial, and coastal
      sites.
AB  - The tandem differential mobility analyzer (TDMA) technique was applied to
      determine the hygroscopicity and volatility of atmospheric ultrafine particles in
      three sites of urban Gwangju, industrial Yeosu, and coastal Taean in South Korea.
      A database for the hygroscopicity and volatility of the known compositions and
      sizes of the laboratory-generated particles wasfirst constructed for comparison
      with the measured properties of atmospheric ultrafine particles. Distinct
      differences in hygroscopicity and volatility of atmospheric ultrafine particles
      werefound between a "photochemical event" and a "combustion event" as well as
      among different sites. At the Gwangju site, ultrafine particles in the
      "photochemical event" were determined to be more hygroscopic (growth factor (GF)
      = 1.05-1.33) than those in the "combustion event" (GF = 1.02-1.12), but their
      hygroscopicity was not as high as pure ammonium sulfate or sulfuric acid
      particles in the laboratory-generated database, suggesting they were internally
      mixed with less soluble species. Ultrafine particles in the "photochemical event"
      at the Yeosu site, having a variety of SO2, CO, and VOC emission sources, were
      more hygroscopic (GF = 1.34-1.60) and had a higher amount of volatile species (47
      75%)than those observed at the Gwangju site. Ultrafine particle concentration at
      the Taean site increased during daylight hours with low tide, having a higher GF
      (1.34-1.80) than the Gwangju site and a lower amount of volatile species (17-34%)
      than the Yeosu site. Occasionally ultrafine particles were externally mixed
      according to their hygroscopicity and volatility, and TEM/EDS data showed that
      each type of particle had a distinct morphology and elemental composition.

PMID- 19764240
TI  - Geophysical monitoring of coupled microbial and geochemical processes during
      stimulated subsurface bioremediation.
AB  - Understanding how microorganisms alter their physical and chemical environment
      during bioremediation is hindered by our inability to resolve subsurface
      microbial activity with high spatial resolution. Here we demonstrate the use of a
      minimally invasive geophysical technique to monitor stimulated microbial activity
      during acetate amendment in an aquifer near Rifle, Colorado. During electrical
      induced polarization (IP) measurements, spatiotemporal variations in the phase
      response between imposed electric current and the resultant electric field
      correlated with changes in groundwater geochemistry accompanying stimulated iron
      and sulfate reduction and sulfide mineral precipitation. The magnitude of the
      phase response varied with measurement frequency (0.125 and 1 Hz) and was
      dependent upon the dominant metabolic process. The spectral effect was
      corroborated using a biostimulated column experiment containing Rifle sediments
      and groundwater. Fluids and sediments recovered from regions exhibiting an
      anomalous phase response were enriched in Fe(II), dissolved sulfide, and cell
      associated FeS nanoparticles. The accumulation of mineral precipitates and
      electroactive ions altered the ability of pore fluids to conduct electrical
      charge, accounting for the anomalous IP response and revealing the usefulness of
      multifrequency IP measurementsfor monitoring mineralogical and geochemical
      changes accompanying stimulated subsurface bioremediation.

PMID- 19764241
TI  - Selective detection of hypertoxic organophosphates pesticides via PDMS composite
      based acetylcholinesterase-inhibition biosensor.
AB  - We report on a pair of highly sensitive amperometric biosensors for
      organophosphate pesticides (OPs) based on assembling acetylcholinesterase (AChE)
      on poly(dimethylsiloxane) (PDMS)-poly(diallydimethylemmonium) (PDDA)/gold
      nanoparticles (AuNPs) composite film. Two AChE immobilization strategies are
      proposed based on the composite film with hydrophobic and hydrophilic surface
      tailored by oxygen plasma. The twin biosensors show interesting different
      electrochemical performances. The hydrophobic surface based PDMS-PDDAN
      AuNPs/choline oxidase (ChO)/AChE biosensor (biosensor-1) shows excellent
      stability and unique selectivity to hypertoxic organophosphate. At optimal
      conditions, this biosensor-1 could measure 5.0 x 10(-10) g/L paraoxon and 1.0 x
      10(-9) g/L parathion. As for the hydrophilic surface based biosensor (biosensor
      2), it shows no selectivity but can be commonly used for the detection of most
      OPs. Based on the structure of AChE, it is assumed that via the hydrophobic
      interaction between enzyme molecules and hydrophobic surface, the enzyme active
      sites surrounded by hydrophobic amino acids face toward the surface and get
      better protection from OPs. This assumption may explain the different
      performances of the twin biosensors and especially the unique selectivity of
      biosensor-1 to hypertoxic OPs. Real sample detection was performed and the
      omethoate residue on Cottomrose Hibiscus leaves was detected with biosensor-1.

PMID- 19764242
TI  - A comparision of laboratory and field based determinations of molecular diffusion
      coefficients in a low permeability geologic medium.
AB  - Molecular diffusion is the dominant transport mechanism for contaminants in many
      saturated clay-rich aquitards. The effective coefficient of diffusion (Da) is
      traditionally determined by conducting laboratory tests on cm-scale core samples
      that may not be representative of the bulk geologic formation. Here we conducted
      the first long-term field based in situ diffusion experimentto compare the effect
      of experimental scale (5 x 10(-5) m3 in the diffusion cells and (5-20) x 10(-2)
      m3 in the in situ experiments) on De values for clay-rich aquitards. Using a
      conservative tracer (deuterium), our testing shows De values estimated from in
      situ testing ((2.5-3.5) x 10(-10) m2 s(-1)) are similar but lower than the
      average De values measured in the laboratory (4 x 10(-10) m2 s(-1)). The
      difference was attributed to greater porosity values in the laboratory samples
      resulting from core barrel extrusion and sample swelling. With representative
      core sampling and care, laboratory-based diffusion testing remains a viable
      method to assess solute transport mechanisms in clay aquitards.

PMID- 19764243
TI  - Effects of diesel exhaust aftertreatment devices on concentrations and size
      distribution of aerosols in underground mine air.
AB  - Three types of uncatalyzed diesel particulate filter (DPF) systems, three types
      of high-temperature disposable filter elements (DFEs), and one diesel oxidation
      catalytic converter (DOC) were evaluated in underground mine conditions for their
      effects on the concentrations and size distributions of diesel aerosols. Those
      effects were compared with the effects of a standard muffler. The experimental
      work was conducted directly in an underground environment using a unique diesel
      laboratory developed in an underground experimental mine. The DPF systems reduced
      total mass of aerosols in the mine air approximately 10-fold for light-load and
      20-fold or more for high-load test conditions. The DFEs offered similar
      reductions in aerosol mass concentrations. The efficiency of the new DFEs
      significantly increased with accumulation of operating time and buildup of diesel
      particulate matter in the porous structure of the filter elements. A single
      laundering process did not exhibit substantial effects on performance of the
      filter element The effectiveness of DPFs and DFEs in removing aerosols by number
      was strongly influenced by engine operating mode. The concentrations of
      nucleation mode aerosols in the mine air were found to be substantially higher
      for both DPFs and DFEs when the engine was operated at high-load modes than at
      low-load modes. The effects of the DOC on mass and number concentrations of
      aerosols in mine air were relatively minor when compared to those of the DPF and
      DFE systems.

PMID- 19764244
TI  - Trichloroethylene transformation in aerobic pyrite suspension: pathways and
      kinetic modeling.
AB  - The pathways and kinetics of trichloroethylene (TCE) degradation in aerobic
      pyrite suspension were investigated. The detection of hydroxyl radical in aqueous
      pyrite suspension suggested that TCE was degraded by this strong oxidant The
      reaction pathways of TCE degradation were proposed in which the degradation of
      TCE to formic acid and finally to CO2 was the main route. Degradation of TCE to
      oxalic acid and to dichloroacetic acid were found as minor pathways. Degradation
      rates of TCE to formic acid, glyoxylic acid, and dichloroacetic acid were
      obtained using kinetic model at 1.2 x 10(-2), 9.8 x 10(-4) and 4.6 x 10(-4) h(
      1), respectively.

PMID- 19764245
TI  - Modeling chlorine isotope trends during sequential transformation of chlorinated
      ethenes.
AB  - There is increasing interest in combined carbon-chlorine compound-specific
      isotope analysis (CSIA)to differentiate between contaminant sources and to assess
      transformation processes. However, the significant abundance of polychlorinated
      molecules with several heavy chlorine isotopes complicates the evaluation of
      chlorine isotope trends. Therefore, the goal of this study was to develop a
      conceptual and mathematical framework that describes the expected chlorine
      isotope fractionation patterns during multistep transformation of chlorinated
      compounds. Reductive dechlorination of chlorinated ethenes served as an example.
      The study demonstrates that chlorine isotope trends can be simulated by
      reproducing the average behavior of light and heavy isotopes or by explicitly
      simulating molecules with different numbers of heavy isotopes (isotopologues).
      The calculations reveal that initial chlorine isotope ratios of products equal
      the isotope ratios of their parent compounds in the absence of secondary isotope
      effects, while steadily increasing during transformation. The slopes in dual
      isotope plots are linear for reactant and product during a one-step reaction.
      They become nonlinear for products that are degraded further but converge to
      characteristic slopes. Consideration of different scenarios reveals that combined
      carbon-chlorine isotope analysis bears high potential to differentiate between
      contaminant sources, to elucidate reaction mechanisms in laboratory studies, and
      to identify transformation processes in the field.

PMID- 19764246
TI  - Titanium nanomaterial removal and release from wastewater treatment plants.
AB  - Titanium (Ti) occurs naturally in soils and as highly purified titanium dioxide
      (Ti5O2) in many commercial products that have been used for decades. We report
      for the first time the occurrence, characterization, and removal of nano- and
      larger-sized Ti at wastewater treatment plants (WWTPs). At one WWTP studied in
      detail, raw sewage contained 100 to nearly 3000 microg TVL Ti larger than 0.7
      microm accounted for the majority of the Ti in raw sewage, and this fraction was
      well removed by WWTP processes. Ti concentrations in effluents from this and
      several other WWTPs ranged from <5 to 15 microg/L and were nearly all present in
      the < 0.7 microm size fraction. As Ti was removed, it accumulated in settled
      solids at concentrations ranging from 1 to 6 microg Ti/mg. Ti-containing solids
      were imaged in sewage, biosolids, and liquid effluent as well as in commercial
      products containing engineered TiO2. Single nanoparticles plus spherical
      aggregates (50 nm to a few hundred nanometer in size) composed of sub-50 nm
      spheres of Ti and oxygen only (presumably TiO2) were observed in all samples.
      Significantly larger silicate particles containing a mixture of Ti and other
      metal atoms were also observed in the samples. To support the field work,
      laboratory adsorption batch and sequencing batch reactor experiments using TiO2
      and activated sludge bacteria verified that adsorption of TiO2 onto activated
      sludge biomass occurs. Monitoring for TiO2 in the environment where WWTP liquid
      effluent is discharged (rivers, lakes, oceans) or biomass disposed (landfills,
      agriculture and soil amendments, incinerator off-gas or residuals) will increase
      our knowledge on the fate and transport of other nanomaterials in the environment

PMID- 19764247
TI  - Bimolecular rate constant determination for the reaction of hydroxyl radicals
      with domoic and kainic acid in aqueous solution.
AB  - Bimolecular rate constants for the hydroxyl radical, .OH, reaction with domoic
      acid, kainic acid, and several model compounds were determined using electron
      pulse radiolysis and transient absorption spectroscopy. These oxidation rate
      constants were determined as (9.22 +/- 0.60) x 10(9) M(-1) s(-1) and (2.46 +/-
      0.19) x 10(9) M(-1) s(-1), for domoic acid and kainic acid, respectively. Model
      compound rate constant measurements suggested that the conjugated double bond of
      the C4 substituent of domoic acid, and the double bond in kainic acid, were the
      preferential initial site of .OH reaction, which would destroy the conjugation
      and/or molecular conformation of these toxins. These reaction rate constants were
      also used to determine potential persistence in natural water systems, however
      the calculated half-life for domoic acid of approximately 34 days implies that
      significant photodegradation via .OH reaction mechanisms is unlikely.

PMID- 19764248
TI  - Solute coupled diffusion in osmotically driven membrane processes.
AB  - Forward osmosis (FO) is an emerging water treatment technology with potential
      applications in desalination and wastewater reclamation. In FO, water is
      extracted from a feed solution using the high osmotic pressure of a hypertonic
      solution that flows on the opposite side of a semipermeable membrane; however,
      solutes diffuse simultaneously through the membrane in both directions and may
      jeopardize the process. In this study, we have comprehensively explored the
      effects of different operating conditions on the forward diffusion of solutes
      commonly found in brackish water and seawater, and reverse diffusion of common
      draw solution solutes. Results show that reverse transport of solutes through
      commercially available FO membranes range between 80 mg to nearly 3,000 mg per
      liter of water produced. Divalent feed solutes have low permeation rates (less
      than 1 mmol/m2-hr) while monovalent ions and uncharged solutes exhibit higher
      permeation. Findings have significant implications on the performance and
      sustainability of the FO process.

PMID- 19764249
TI  - Treatment of fluoroacetate by a Pseudomonas fluorescens bioflm grown in membrane
      aerated biofilm reactor.
AB  - Fluorinated organic compounds have widespread applications, and their
      accumulation in the environment is a concern. Biofilm reactors are an effective
      technology for the treatment of contaminated wastewater, yet almost no research
      has been conducted on the effectiveness of biofilms for the biodegradation of
      fluorinated aliphatic compounds. In this paper we describe experiments undertaken
      to investigate the degradation of fluoroacetate using a membrane aerated biofilm
      reactor (MABR) by Pseudomonas fluorescens DSM8341. The concentration of
      fluoroacetate in the medium influenced biofilm structure, with less dense biofilm
      observed at lower fluoroacetate loading rates. As biofilm thickness increased,
      oxygen utilization decreased, probably as a consequence of increased resistance
      to oxygen transfer. Furthermore, most of the biofilm was anaerobic, since oxygen
      penetration depth was less than 1000 microm. Biofilm performance, in terms of
      fluoroacetate removal efficiency, was improved by decreasing the fluoroacetate
      loading rate, however increasing the intramembrane oxygen pressure had little
      effect on biofilm performance. A mathematical model showed that while
      fluoroacetate does not penetrate the entire biofilm, the defluorination
      intermediate metabolite glycolate does, and consequently the biofilm was not
      carbon limited at the biofilm-membrane interface where oxygen concentrations were
      highest The model also showed the accumulation of the free fluoride ion within
      the biofilm. Overflow metabolism of glycolate was identified to be most likely a
      result of a combination of oxygen limitation and free fluoride ion inhibition.
      The study demonstrated the potential of MABR for treating wastewater streams
      contaminated with organofluorine compounds.

PMID- 19764250
TI  - Assessment of long-term performance and chromate reduction mechanisms in a field
      scale permeable reactive barrier.
AB  - An innovative full-scale implementation of a permeable reactive barrier,
      consisting of a double-row of cylinders filled with zerovalent iron shavings, for
      chromate remediation was monitored over four years. Solid samples were analyzed
      to elucidate (i) the relevant corrosion mechanisms and products, (ii) the
      pathways of chromate reduction and immobilization, and (iii) the long-term
      performance of the barrier situated in a hydrological and geochemical complex
      groundwater regime. Sampling and analysis of groundwater and reactive material
      revealed an oxidative iron corrosion zone evolving in the inflow and a zone of
      anaerobic iron corrosion in the center and outflow of the barrier. Chromate
      reduction was mainly confined to the inflow region. The formation and thickness
      of corrosion rinds depended on sampling time, position, and depth, as well as on
      the size, shape, and graphite content In the inflow, the corrosion rinds mostly
      consisted of goethite and ferrihydrite. X-ray absorption fine structure
      spectroscopy revealed two distinct Cr(III) species, most likely resulting from
      homogeneous and heterogeneous redox reaction pathways, respectively. The
      longevity and long-term effectiveness of the PRB appears to be primarily limited
      by reduced corrosion rates of the ZVI-shavings because of the thick layers of Fe
      hydroxides.

PMID- 19764251
TI  - Simple and efficient sonochemical method for the oxidation of arsenic(III) to
      arsenic(V).
AB  - A simple and efficient sonochemical method has been developed for the oxidation
      of acutely toxic As(III) to the less toxic As(V). The OH radicals produced during
      acoustic cavitation readily oxidize As(III) to As(V) in an aqueous environment
      The effects of various operational parameters of ultrasonication, such as power
      density and pulse mode, on the oxidation of As(III) were studied. Pulsed
      sonication showed a profound effect on the oxidation of As(III) to As(V) in
      comparison to the continuous mode of operation, that consequently reduced the
      reaction time and energy requirement for the process. Increasing acoustic
      amplitude led to an enhanced rate of oxidation of As(III). In the presence of
      As(III), the production of H2O2 was significantly reduced compared to that
      observed during the sonication of water alone, which suggests that OH radicals
      were involved in the oxidation process. The oxidation of As(III) was independent
      of the initial pH of the solution in the range 3 to 10.6. Continuous sparging of
      nitrogen through the reaction solution noticeably reduced the oxidation rate of
      As(III), indicating thatdissolved oxygen is involved in the oxidation process to
      a certain extent. It is concluded thatthe sonochemical treatment process is a
      simple and possibly cost-effective technique for the oxidation of As(III) to
      As(V) without assistance of any external chemicals or catalysts.

PMID- 19764252
TI  - 1,1,1-trichloroethane and 1,1-dichloroethane reductive dechlorination kinetics
      and co-contaminant effects in a Dehalobacter-containing mixed culture.
AB  - 1,1,1-Trichloroethane (1,1,1-TCA) is a common groundwater contaminant that can be
      reductively dechlorinated to 1,1-dichloroethane (1,1-DCA) and monochloroethane,
      and can support the growth of certain dehalorespiring strains of Dehalobacter We
      used reductive dehalogenase cell-free extract assays (with reduced methyl
      viologen) and whole cell suspension dechlorination assays (with hydrogen) and a
      Dehalobacter-containing enrichment culture to explore the kinetics of l,1,1-TCA
      and 1,1-DCA reductive dechlorination in the presence of the common co
      contaminants trichloroethene (TCE), cis-dichloroethene (cDCE), and vinyl chloride
      (VC). These chlorinated ethenes were most significant inhibitors of 1,1,1-TCA
      dechlorination in cell-free extracts, indicating direct effects on the reductive
      dehalogenase enzyme(s). The inhibition was present but less pronounced in whole
      cell suspension assays. None of the chlorinated ethenes inhibited 1,1-DCA
      dechlorination in cell-free extract assays, yet cDCE and particularly VC were
      inhibitors in whole cell assays, indicating an effect on Dehalobacter, but not on
      the dehalogenase enzyme(s). Marked differences in kinetic parameters for 1,1,1
      TCA and 1,1-DCA, and an uncoupling of these two activities in cultures grown on
      1,1-DCA compared to those grown on 1,1,1-TCA was strong evidence for the
      existence of distinct 1,1,1-TCA and 1,1-DCA reductive dehalogenase enzymes.

PMID- 19764253
TI  - Evidencing generation of persistent ozonation products of antibiotics
      roxithromycin and trimethoprim.
AB  - The mechanism of product formation during ozonation of two widely used
      antimicrobial agents, macrolide roxithromycin and inhibitor of dihydrofolate
      reductase (DHFR) trimethoprim was studied in laboratory-scale experiments with
      two types of matrix: distilled water and secondary wastewater effluent The
      structures ofthe primary and secondary reaction intermediates were elucidated
      byquadrupole-time-of-flight (QqToF) instrument, showing that in spite of their
      high ozone affinity both roxithromycin and trimethoprim oxidation pathway involve
      to a great degree the *OH radical chain reactions. In total nine ozonation
      products were detected, whereas two products of roxithromycin exhibited high
      refractoriness to ozonation, especially in the case of distilled water.
      Furthermore, the intact tertiary amine moiety of roxithromycin in these products
      suggests that the antimicrobial activity of the parent compound will be
      preserved.

PMID- 19764254
TI  - Recovery of biosolids from constructed wetlands used for faecal sludge dewatering
      in tropical regions.
AB  - Biosolids recovered from yard-scale vertical-flow constructed wetlands used for
      faecal sludge dewatering in Cameroon, were analyzed to assess their degree of
      maturity, nutrient and heavy metals contents, as well as their hygienic quality.
      Six beds were loaded weekly at nominal loading rate of 100, 200, and 300 kg
      TS/m2/year. The quality of the biosolids accumulated in the beds was monitored
      during 6 additional months of resting period prior to final harvest. Results
      showed that C/N ratio (11.3), humification index (14%), humification rate (1.8%),
      and degree of polymerization (3.7) of the biosolids generated were comparable to
      those of mature composts. Biosolids quality appeared to having high fertilizing
      value (N: 2%, P2O5: 2.3%, CaO: 1%, MgO: 0.14%, K2O: 0.03, and Na2O: 0.09%) with
      low heavy metals contamination (63, 14, 26, 2.4, 575, 703, 186, and 32 mg/kg for
      Pb, Ni, Cr, Cd, Cu, Zn, Mn, and Se, respectively). The concentration of fertile
      ascaris was reduced from 40 eggs/g TS after one month storage to <4 eggs/g TS
      after six month of storage, a level which does not significantly increase health
      risk exposure as compare to the WHO guidelines.

PMID- 19764255
TI  - Accumulated metal speciation in earthworm populations with multigenerational
      exposure to metalliferous soils: cell fractionation and high-energy synchrotron
      analyses.
AB  - Predicting metal bioaccumulation and toxicity in soil organisms is complicated by
      site-specific biotic and abiotic parameters. In this study we exploited tissue
      fractionation and digestion techniques, combined with X-ray absorption
      spectroscopy (XAS), to investigate the whole-body and subcellular distributions,
      ligand affinities, and coordination chemistry of accumulated Pb and Zn in field
      populations of the epigeic earthworm Lumbricus rubellus inhabiting three
      contrasting metalliferous and two unpolluted soils. Our main findings were (i)
      earthworms were resident in soils with concentrations of Pb and Zn ranging from
      1200 to 27,000 mg kg(-1) and 200 to 34,000 mg kg(-1), respectively; (ii) Pb and
      Zn primarily accumulated in the posterior alimentary canal in nonsoluble
      subcellular fractions of earthworms; (iii) site-specific differences in the
      tissue and subcellular partitioning profiles of populations were observed, with
      earthworms from a calcareous site partitioning proportionally more Pb to their
      anterior body segments and Zn to the chloragosome-rich subcellular fraction than
      their acidic-soil inhabiting counterparts; (iv) XAS indicated that the
      interpopulation differences in metal partitioning between organs were not
      accompanied by qualitative differences in ligand-binding speciation, because
      crystalline phosphate-containing pyromorphite was a predominant chemical species
      in the whole-worm tissues of all mine soil residents. Differences in metal (Pb,
      Zn) partitioning at both organ and cellular levels displayed by field populations
      with protracted histories of metal exposures may reflect theirinnate
      ecophysiological responses to essential edaphic variables, such as Ca2+ status.
      These observations are highly significant in the challenging exercise of
      interpreting holistic biomarker data delivered by "omic" technologies.

PMID- 19764256
TI  - Physiological modes of action of fluoxetine and its human metabolites in algae.
AB  - Fluoxetine, the active ingredient of many antidepressants, was identified as
      specifically toxic toward algae in a quantitative structure-activity relationship
      (QSAR) analysis with literature data for algae, daphnia, and fish. The goal of
      this study was to elucidate the mode of action in algae and to evaluate the
      toxicity of the major human metabolites of fluoxetine using two different algae
      tests. The time dependence and sensitivity of thedifferenteffectendpointsyield
      information on the physiological mode of action. Baseline toxicity was predicted
      with QSARs based on measured liposome-water partition coefficients. The ratio of
      predicted baseline toxicity to experimental toxicity (toxic ratio TR) gives
      information on the intrinsic potency (extent of specificity of effect). The
      metabolite p-trifluoromethylphenol was classified to act as baseline toxicant
      Fluoxetine (TR 60-150) and its pharmacologically active metabolite norfluoxetine
      (TR 10-80) exhibited specific toxicity. By comparison with reference compounds we
      conclude that fluoxetine and norfluoxetine have an effect on the energy budget of
      algal cells since the time pattern of these two compounds is most similar to that
      observed for norflurazon, but they act less specifically as indicated by lower TR
      values and the similarity of the effect pattern to baseline toxicants. The
      mixture toxicity of fluoxetine and its human metabolites norfluoxetine and p-TFMP
      can be predicted using the model of concentration addition for practical purposes
      of risk assessment despite small deviations from this model for the specific
      endpoints like PSII inhibition because the integrative endpoints like growth rate
      and reproduction in all cases gave agreement with the predictions for
      concentration addition.

PMID- 19764257
TI  - Toxic and accumulative potential of the antifouling biocide and TBT successor
      irgarol on freshwater macrophytes: a pond mesocosm study.
AB  - After the ban of tributyltin (TBT) for vessels not longer than 25 m in 1986,
      Irgarol has become a commonly used antifouling biocide. Irgarol is highly toxic
      to autotrophic organisms and has the potential to accumulate in organic material.
      In the literature, environmental concentrations of Irgarol up to 2.4 microg L(-1)
      were reported forfreshwater. Within a comprehensive freshwater mesocosm study,
      experiments were conducted to gain more information on the effects of Irgarol on
      macrophytes. Six indoor pond mesocosms were contaminated once with concentrations
      between 0.04 and 5 microgl(-1) Irgarol and monitored for 150 days; two mesocosms
      served as controls. The mesocosm study revealed that all macrophytes were
      directly affected by this single application. Myriophyllum verticillatum was the
      most sensitive macrophyte with an EC50 (Day 150) of 0.21 microg L(-1) Irgarol.
      The duckweed Spirodela polyrhiza was the least sensitive species tested in the
      mesocosms and number of fronds even increased with increasing Irgarol
      concentrations. Time-weighted average calculations yielded high BCF values of up
      to 10,580 L kg(-1) dry weight for M. verticillatum indicating a high potential
      for accumulation. The results give cause for concern that natural macrophyte
      communities are impaired at actual environmental concentrations.

PMID- 19764258
TI  - Simple, rapid zebrafish larva bioassay for assessing the potential of chemical
      pollutants and drugs to disrupt thyroid gland function.
AB  - Thyroid function may be altered by a very large number of chemicals routinely
      found in the environment Research evaluating potential thyroid disruption is
      ongoing, but there are thousands of synthetic and naturally occurring drugs and
      chemicals to be considered. European and United States policies call for the
      development of simple methodologies for screening endocrine-disrupting chemicals.
      Zebrafish are widely used as a model organism for assessing drug effects because
      of their small size, high fecundity, rapid organogenesis, morphological and
      physiological similarities to mammals, and easewithwhich large-scale phenotypic
      screening is performed. A zebrafish-based short-duration screening method was
      developed to detect the potential effect of chemicals and drugs on thyroid
      function. This method used a T4 immunofluorescence quantitative disruption test
      (TIQDT) to measure thyroid function. The 3 day exposure window protocol, from day
      2 to day 5 postfertilization (dpf), avoided any potential side effects on thyroid
      gland morphogenesis. Methimazole, propylthiouracil, and potassium perchlorate,
      three well-known goitrogens, totally abolished T4 immunoreactivity in thyroid
      follicles in a dose-specific manner. Amiodarone, a human pharmaceutical with a
      reported cytotoxic effect on thyroid follicular cells, also decreased T4 levels.
      Moreover, exposure to 50 nM 3,3',5-triiodothyronine induced a significant
      decrease in T4 immunoreactivity as did DDT, 2,4-D, and 4-nonylphenol. In
      conclusion, these data indicated that TIQDT may be useful for obtaining initial
      information about the ability of environmental pollutants and drugs to impair
      thyroid gland function as well as assessing the combined effects of endocrine
      disruptors.

PMID- 19764259
TI  - Size distributions of polycyclic aromatic hydrocarbons in the atmosphere and
      estimation of the contribution of ultrafine particles to their lung deposition.
AB  - This is the first estimation of the contribution of ultrafine particles to the
      lung deposition of particle-bound polycyclic aromatic hydrocarbons (PAHs) in the
      atmosphere. The size distributions of nine PAHs (4-6 rings) were measured at
      roadside and suburban sites in winter in Japan. Deposition efficiencies and
      fluxes of PAHs in ultrafine mode (<0.12 microm), accumulation mode (0.12-2.1
      microm), and coarse mode (>2.1 microm) to the human respiratory tract were
      calculated using the LUDEP computer-based model. From 10%-15% and 4.2%-6.9% of
      target PAHs were distributed in the ultrafine mode in the roadside and suburban
      atmosphere, respectively. The model calculations showed that as much as 18%-19%
      and 16%-17% of inhaled PAHs are deposited in the alveolar region of the lung for
      the roadside and suburban atmosphere, respectively. Total deposition fluxes of
      target PAHs in the alveolar region were about 1.5-fold greater for the roadside
      atmosphere than for the suburban atmosphere. Importantly, ultrafine particles
      were shown to contribute as much as 23%-30% and 10%-16% to PAH deposition in the
      alveolar region for the roadside and suburban atmosphere, respectively, although
      the contributions of ultrafine particles to the total particulate matter masswere
      only 2.3% in the roadside atmosphere and 1.3% in the suburban atmosphere. These
      results indicated that ultrafine particles are significant contributors to the
      deposition of PAHs into the alveolar region of the lung.

PMID- 19764260
TI  - Do toxicity identification and evaluation laboratory-based methods reflect causes
      of field impairment?
AB  - Sediment toxicity identification and evaluation (TIE) methods are relatively
      simple laboratory methods designed to identify specific toxicants or classes of
      toxicants in sediments; however, the question of whether the same toxicant
      identified in the laboratory is causing effects in the field remains unanswered.
      The objective of our study was to determine if laboratory TIE methods accurately
      reflect field effects. A TIE performed on sediments collected from the Elizabeth
      River (ER) in Virginia identified polycyclic aromatic hydrocarbons (PAHs) as the
      major toxicants. Several lines of evidence indicated PAHs were the major toxic
      agents in the field, including elevated PAH concentrations in ER sediments, comet
      assay results from in situ caged Merceneria merceneria, and chemical analyses of
      exposed M. merceneria, which indicated high PAH concentrations in the bivalve
      tissue. Our final evidence was the response from test organisms exposed to ER
      sediment extracts and then ultraviolet (UV) radiation. UV radiation caused a
      toxic diagnostic response unique to PAHs. The aggregation of these various lines
      of evidence supports the conclusion that PAHs were the likely cause of effects in
      laboratory- and field-exposed organisms, and that laboratory-based TIE findings
      reflect causes of field impairment

PMID- 19764261
TI  - An ecotoxicological study of poly(amidoamine) dendrimers-toward quantitative
      structure activity relationships.
AB  - Polyamidoamine (PAMAM) dendrimers of generation 6-4, G-5 and G-6 were evaluated
      for their aquatic toxicity using the test models Vibrio fischeri, Daphnia magna,
      Thamnocephalus platyurus, and two fish cell lines. Physico-chemical
      characterization of the particles in each of the different test media was
      performed. A significant eco- and cytotoxicological response was recorded at
      concentrations from 0.129 microM (7.4 mg L(-1)) to 16.30 microM (231.5 mg L(-1)).
      Daphnia magna was found to be the most sensitive test model, the RTG-2 fish cell
      line the least. The toxicological response correlated well with the dendrimer
      generation and therefore with the particle surface area, increasing surface area
      leading to increased toxic response. The response also correlated well with
      changes to the 4 potential in the different media, rather than the actual 4
      potential, indicating a potential contribution of changes to the effective
      composition of the medium. For the cell lines, although spectroscopic studies
      indicated an interaction with the serum supplement, trends for this interaction
      do not correlate to those observed for the toxic response. The clear correlations
      of the observed toxicresponse with themeasured physicochemical properties
      pointtoward underlying structure activity relationships.

PMID- 19764262
TI  - Use of carbon mesh anodes and the effect of different pretreatment methods on
      power production in microbial fuel cells.
AB  - Flat electrodes are useful in microbial fuel cells (MFCs) as close electrode
      spacing improves power generation. Carbon cloth and carbon paper materials
      typically used in hydrogen fuel cells, however, are prohibitively expensive for
      use in MFCs. An inexpensive carbon mesh material was examined here as a
      substantially less expensive alternative to these materials for the anode in an
      MFC. Pretreatment of the carbon mesh was needed to ensure adequate MFC
      performance. Heating the carbon mesh in a muffle furnace (450 degrees C for 30
      min) resulted in a maximum power density of 922 mW/m2 (46 W/m3) with this heat
      treated anode, which was 3% more power than that produced using a mesh anode
      cleaned with acetone (893 mW/ m2; 45 W/m3). This power density with heating was
      only 7% less than that achieved with carbon cloth treated by a high temperature
      ammonia gas process (988 mW/m2; 49 W/m3). When the carbon mesh was treated by the
      ammonia gas process, power increased to 1015 mW/m2(51 W/m3). Analysis of the
      cleaned or heated surfaces showed these processes decreased atomic O/C ratio,
      indicating removal of contaminants that interfered with charge transfer. Ammonia
      gas treatment also increased the atomic N/C ratio, suggesting that this process
      produced nitrogen related functional groups that facilitated electron transfer.
      These results show that low cost heat-treated carbon mesh materials can be used
      as the anode in an MFC, providing good performance and even exceeding performance
      of carbon cloth anodes.

PMID- 19764263
TI  - Effects of idle reduction technologies on real world fuel use and exhaust
      emissions of idling long-haul trucks.
AB  - Idling long-haul freight tucks may consume nearly one billion gallons of diesel
      fuel per year in the U.S. There is a need for real-world data by which to
      quantify avoided fuel use and emissions attributable to idle reduction techniques
      of auxiliary power units (APUs) and shore-power (SP). Field data were obtained
      from 20 APU-equipped and SP-compatible trucks observed during 2.8 million miles
      of travel in 42 states. Base engine fuel use and emission rates varied depending
      on ambient temperature. APU and SP energy use and emission rates varied depending
      on electrical load. APUs reduced idling fuel use and CO2 emissions for single and
      team drivers by 22 and 5% annually, respectively. SP offers greater reductions in
      energy use of 48% for single drivers, as well as in emissions, except for SO2.
      APUs were cost-effective for single drivers with a large number of APU usage
      hours per year, but not for team drivers or for single drivers with low APU
      utilization rates. The findings support more accurate assessments of avoided fuel
      use and emissions, and recommendations to encourage greater APU utilization by
      single drivers and to further develop infrastructure for SP.

PMID- 19764264
TI  - Use of biocompatible buffers to reduce the concentration overpotential for
      hydrogen evolution.
AB  - The hydrogen evolution reaction (HER) at Pt-cathodes of microbial electrolysis
      cells (MEC) has been associated with overpotentials of several hundred
      millivolts. The high overpotentials challenge the sustainability of an MEC. This
      paper shows that the HER overpotential at MEC relevant pH values is reduced if
      buffer is present At 15 A/m2 and 50 mM buffer, the lowest overpotential for
      phosphate was -0.05 V at pH 6.2, for ammonia was -0.05 V at pH 9.0, for carbonate
      was -0.09 V at pH 9.3, for Tris(hydroxymethyl)aminomethane was -0.07 V at pH 7.8,
      and for N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid was -0.08 V at pH
      7.2. It was shown that the effect of buffer on the overpotentialis strongly pH
      dependent Furthermore, experimental data and a mass transport equation showed
      that by increasing the buffer concentration or linear flow speed (i.e., pump
      speed), or decreasing the current density (i) the overpotential reduces and (ii)
      the minimum overpotential is reached at a pH that approaches the buffer
      dissociation constant (pKa). Thus, to reduce the HER overpotential of an MEC,
      buffer (i.e., pKa), buffer concentration, linear flow speed, and current density
      must be well balanced with the expected operational pH.

PMID- 19764265
TI  - Practical potential of reverse electrodialysis as process for sustainable energy
      generation.
AB  - Reverse electrodialysis (RED) is a nonpolluting sustainable technology that
      converts the free energy of mixing of two solutions with different salinity
      directly into electrical energy. Although the theoretical potential is high, the
      practical power output obtained is limited yet due to concentration polarization
      phenomena and spacer shadow effects. In this work we combinetheoretical
      calculations with direct current and alternating current experimental stack
      characterization methods to quantify the contribution of concentration
      polarization phenomena, spacer shadow effects and stack resistance in RED under
      different hydrodynamic conditions in a temperature range from 10 to 40 degrees C
      to show the practical potential of RED. Concentration polarization phenomena play
      an important role and their influence can be minimized by optimal stack
      hydrodynamics. Improved spacerdesigns and newspacerconceptsofferextensive room to
      reduce the spacer shadow effect and to further increase the practical power
      output Improvement of hydrodynamics and reduction of the spacer shadow effect
      directly result in a significant increase in power output of the RED process, and
      values almost double the values currently obtained can be realized, which brings
      RED close to economical viability.

PMID- 19764266
TI  - Links between parent characteristics and attachment variables for college
      students of parental divorce.
AB  - This study investigated links between offsprings' attachment patterns and parent
      characteristics in 157 females and 62 males of parental divorce. Secure females
      and males reported affection, respect, and closeness toward both biological
      parents. Offsprings' insecure attachment pattern was associated with negative
      parent characteristics. Participants who perceived their same-sex parent
      negatively were more likely to report an insecure attachment. Our findings
      suggest delayed negative consequences of parental divorce for college women and
      men.

PMID- 19764267
TI  - Teachers' preferences for interventions for ethnically diverse learners with
      attention-deficit hyperactivity disorder.
AB  - One hundred sixty-eight elementary and middle school teachers participated in
      this investigation on the impact of student gender and ethnicity on teacher
      recommendations for interventions for attention-deficit hyperactivity disorder
      (ADHD). Participants read a scenario describing a student with ADHD accompanied
      by a student photo which depicted his/her ethnicity and gender. Participants were
      then asked how strongly they would recommend four common interventions. Findings
      suggest teachers are more likely to recommend interventions requiring less
      parental involvement for minority students than for Caucasian students.
      Elementary and special education teachers were more likely to recommend
      interventions with greater empirical support than were middle school and regular
      education teachers. Ramifications for intervention selection in schools and
      suggestions for future investigations are reviewed.

PMID- 19764268
TI  - Students' perceptions of the non-academic advantages and disadvantages of
      participation in Advanced Placement courses and International Baccalaureate
      programs.
AB  - In-depth interviews of students with qualitative analysis of the responses were
      used to explore perceptions of the non-academic advantages and disadvantages of
      Advanced Placement (AP) and International Baccalaureate (IB) program
      participation, and differences between the AP and IB programs in those
      perceptions. Results revealed that benefits of participation, including pride in
      completing more challenging work, similarity and special bonds among
      participants, better treatment (more respect and responsibility) from teachers,
      better overall class atmosphere, and preference for AP and IB courses were
      consistent across schools and between programs. Also consistent were the
      disadvantages students reported, with marked differences in the intensity of
      disadvantages between the AP and IB programs. Specifically, as the amount of time
      students spent in homogeneously grouped settings increased, so did the workload,
      the intensity of the perceived social/emotional disadvantages of the workload,
      the perceived range of negative feelings between participants and non
      participants, and the perceived negativity of participant strereotypes.

PMID- 19764269
TI  - Mexican American adolescents' academic achievement and aspirations: the role of
      perceived parental educational involvement, acculturation, and self-esteem.
AB  - As the number of Mexican American school-aged children continues to increase,
      researchers, practitioners, and policymakers are in critical need of information
      to better understand and serve them. This study used structural equation modeling
      to examine the relationship among perceived parental educational involvement
      (PPEI), acculturation, gender, and self-esteem on the academic achievement and
      aspirations of Mexican American high school students (N = 298). Results revealed
      direct effects of perceived parental educational involvement, students' level of
      acculturation, and students' self-esteem on students' achievement and
      aspirations. Acculturation and self-esteem also revealed indirect effects on
      aspirations and achievement through parental educational expectations.
      Implications of these findings are discussed.

PMID- 19764270
TI  - Peer-support suicide prevention in a non-metropolitan U.S. community.
AB  - Though suicide is a leading cause of death for high school age youth, the overall
      base rates for suicide deaths are relatively low. Consequently, very few evidence
      based suicide prevention programs that address suicide death have emerged.
      Relative to urban areas, non-metropolitan and rural communities in particular
      tend to report higher suicide rates that are compounded by poor access to mental
      health care. In the current study, 63 high school youth participated in the three
      day, LifeSavers peer-support suicide prevention training program. The goals of
      the program are to teach youth to engage in teamwork and listen to others without
      judgment in addition to recognizing the signs for youth who may be at risk for
      suicide. The overall aim of LifeSavers is to create a culture whereby primary
      prevention is active and crisis situations are preempted. Each participant in the
      current study completed pre-test and posttraining measures of suicide attitudes
      and knowledge, self-esteem, and also self-acceptance. Findings demonstrated a
      significant increase in knowledge and positive attitudes toward suicide
      prevention and also self-esteem, but not self-acceptance. Though more work is
      needed, these preliminary data reveal that youth in rural communities may benefit
      from programming such as LifeSavers that commit to advancing peer support and
      peer-gatekeeping efforts.

PMID- 19764271
TI  - Bully/victim problems in Northern Ireland's schools: data from the 2003 Young
      Persons' Behavior and Attitude Survey.
AB  - McGuckin and Lewis (2003, 2006, 2008), Mc Guckin, Lewis and Cummins (under review
      b) have reported that little is known about the nature, incidence and correlates
      of bully/victim problems in the Northern Ireland school system. The aim of the
      present study was to examine the prevalence of self-reported experiences of
      bully/victim problems among a representative sample of 7,223 11- to 16-year-olds
      living in Northern Ireland who participated in the 2003 Young Persons' Behaviour
      and Attitude Survey (YPBAS: Northern Ireland Statistics and Research Agency
      [NISRA], 2003). Respondents were presented with three questions inquiring
      explicitly and three questions inquiring implicitly about bully/victim problems.
      Among other questions, respondents volunteered other salient information about
      personal experiences of bully/victim problems (i.e., through use of the "other"
      response option). Almost one-fifth of all respondents (17.2%, n = 1,026) reported
      being a victim of bullying behavior, and 8.1% (n = 492) reported that they had
      picked on or bullied another school pupil. Bully/victim problems also pervaded
      personal experiences of school meal times, sporting activities, and perceptions
      of personal safety. These findings are placed within the context of previous
      findings.

PMID- 19764272
TI  - Evaluation of an Internet addiction treatment program for Chinese adolescents in
      Hong Kong.
AB  - This paper described an indigenous multi-level counseling program designed for
      young people with Internet addiction problems based on the responses of 59
      clients. Regarding objective outcome evaluation, pretest and posttest data
      generally showed that the Internet addiction problems of the participants
      decreased after joining the program and there were some slight positive changes
      in the parenting attributes. For the subjective outcome evaluation findings,
      participants generally perceived that the program was helpful. Findings based on
      these two evaluation strategies suggest this multi-level indigenous counseling
      program has promise for helping young people with Internet addiction problems.

PMID- 19764273
TI  - The effects of program characteristics and psychological engagement on service
      learning outcomes: a study of university students in Hong Kong.
AB  - This study examines the ways in which program characteristics (i.e., involvement
      with service users, agency support, and class experience) and psychological
      engagement interact in university students to affect service-learning outcomes in
      such areas as personal development and civic commitment. The basic premise is
      that these two sets of variables may have differing effects on the outcomes. To
      test this premise, the study employed survey data collected from 113 university
      students participating in a service-learning program in Hong Kong. The results
      support the hypothesis that involvement with service users and psychological
      engagement are the strongest predictors of student outcomes. On the other hand,
      no support is found for the possibility that agency support and class experience
      might affect the outcomes. Implications of the findings for further research and
      future development of service-learning programs are discussed.

PMID- 19764274
TI  - Social problem solving, family functioning, and suicidal ideation among Chinese
      adolescents in Hong Kong.
AB  - Based on the responses of 5,557 Chinese secondary students in Hong Kong, the
      relationship among social problem solving, perceived family functioning, and
      suicidal ideation were examined in this study. Results showed that suicidal
      ideation was negatively related to social problem solving and family functioning.
      It was further found that the linkage between social problem solving and
      adolescent suicidal ideation was stronger under high family functioning relative
      to low family functioning, thus suggesting the moderating effect of family
      functioning on the effect of social problem solving on suicidal ideation. The
      theoretical and practical implications of the findings are discussed.

PMID- 19764275
TI  - Similarities and differences in physical self-concept of males and females during
      late adolescence and early adulthood.
AB  - The purpose of this study was to examine age and sex differences in physical self
      concept of Turkish late adolescents and early adults. A total of 715 high school
      and 1,125 university students voluntarily participated and were administered the
      Physical Self-Description Questionnaire. The findings indicate significant sex
      and age differences on multiple dimensions of physical self, and that males and
      high school students scored higher on almost all subscales of physical self.
      However, analysis did not reveal any significant age and sex interactions on
      physical self. In conclusion, males and females differ from each other on how
      they perceived themselves on the multiple dimensions of physical self, and
      developmental age changes were evident in physical self.

PMID- 19764276
TI  - The role of sense of coherence and physical activity in positive and negative
      affect of Turkish adolescents.
AB  - This study investigated the role of sense of coherence and total physical
      activity in positive and negative affect. Participants were 376 (169 female, 206
      male, and 1 missing value) student volunteers from different faculties of Middle
      East Technical University. Three questionnaires: Sense of Coherence Scale (SOC),
      Physical Activity Assessment Questionnaire (PAAQ), and Positive and Negative
      Affect Schedule (PANAS) were administered to the students together with the
      demographic information sheet. Two separate stepwise multiple linear regression
      analyses were conducted to examine the predictive power of sense of coherence and
      total physical activity on positive and negative affect scores. Results revealed
      that both sense of coherence and total physical activity predicted the positive
      affect whereas only the sense of coherence predicted the negative affect on
      university students. Findings are discussed in light of sense of coherence,
      physical activity, and positive and negative affect literature.

PMID- 19764277
TI  - Anger as a predictor of suicidal ideation in middle-school students in Korea:
      gender difference in threshold point.
AB  - Studies on gender differences in suicidal ideation and anger are limited.
      Furthermore, these studies focused on linear relationships, which limits the full
      understanding of the complex relationships and hampers identification of high
      risk groups for suicidal tendencies. Hence, this study aims to assess the gender
      differences in: (1) the level of suicidal ideation and anger; (2) predictors for
      suicidal ideation; and (3) the varying association between suicidal ideation and
      anger. The target population for this cross-sectional, correlational study was
      adolescents aged 13 to 15 years living in South Korea. A total of 258 adolescents
      (160 boys and 98 girls) completed the Multidimensional Anger Inventory and
      Suicidal Ideation Questionnaire. Data were analyzed by descriptive statistics,
      multiple linear, and spline regression analysis. Girls reported significantly
      higher scores in both anger and suicidal ideation. While anger was a significant
      predictor for suicidal ideation only in boys, both school life satisfaction and
      anger were significant predictors of suicidal ideation in girls. After
      controlling for sociodemographic factors, the spline regression revealed a
      significant threshold point in the relationship between anger and suicidal
      ideation, particularly among girls. At the threshold anger point of 117.67, 12.5%
      of girls belonged to the high-risk group. The gender-specific patterns of the
      relationship between suicidal ideation and anger and the existence of threshold
      points confirmed the need for targeted suicidal preventive programs focusing on
      controlling anger.

PMID- 19764278
TI  - Building mutual aid among young people with emotional and behavioral problems:
      the experiences of Hong Kong social workers.
AB  - Among young people with emotional and behavioral problems (EBP), mutual aid is
      likely to be valuable in their rehabilitation and deserving of social work
      support. The benefits of mutual aid stem from the possibility that it prolongs
      the effective contribution of social work service. Given its potential benefits,
      it is imperative to clarify the ways in which social work service maximizes these
      benefits. Such clarification is necessary both to verify untested theories about
      social work inputs to mutual aid and because the research literature on mutual
      aid among young people is particularly lacking. Based on data from three focus
      groups involving social workers in Hong Kong, this study seeks to demonstrate the
      relevance of theoretically based group work strategies in the mutual aid and
      rehabilitation of EBP youth. These strategies include identifying commonalities
      and setting prioritiese, balancing support with demand, optimizing input between
      social workers and members, and connecting members with relevant others in the
      community. The research and service implications of the findings of this study
      for promoting efficient social work input that contributes to the long-term
      development of young people are discussed.

PMID- 19764279
TI  - Empowering school personnel for positive youth development: the case of Hong Kong
      school social workers.
AB  - While empowerment has become a popular concept in working with adolescents, few
      attempts have been made to explore the possibilities for empowering school
      personnel to create an environment in which young people can make maximum use of
      the opportunity to learn and grow. Based on the field experiences of 15 Hong Kong
      school social workers, this article examines how practitioners use various
      strategies to interact with school personnel to generate empowering practices in
      the school setting: namely, (1) exerting influence on school personnel in daily
      conversations and interactions; (2) creating an environment conducive to the
      teacher-student relationship; (3) achieving consensus with school personnel
      through lobbying and negotiation; and (4) collaborating with school personnel to
      organize life education and positive youth development programs. The findings
      provide valuable reference materials to guide other practitioners in applying the
      empowerment approach in actual practice. It also helps fill the gap in existing
      literature on empowerment and school social work.

PMID- 19764280
TI  - Parental social position, body image, and other psychosocial determinants and
      first sexual intercourse among 15- and 16-year olds.
AB  - This study investigated the associations among first sexual intercourse and body
      image, future educational plans, depressed moods, as well as the influence of
      parental education and income. These associations were tested by gender and
      ethnicity and adjusted for variables likely to affect the findings, such as
      perceived social support, sexual abuse, and age. Tenth graders from Lower
      Secondary Schools in Oslo enrolled in 2000 and 2001 were invited to participate
      in this cross-sectional in-school study (participation rate: 88%). Out of the
      7,343 participants, only those 15 or 16 years of age were included in the
      analyses (N = 7,187). Data on both parents' level of education and income were
      obtained from official registries. Body image was independently associated with
      sexual intercourse for adolescent girls. Those with high scores on body image
      concerns were more likely to have experienced first intercourse. For both male
      and female adolescents, future education plans including higher education were
      negatively associated with first sexual intercourse. Depressed mood and sexual
      abuse had positive associations with reported first sexual intercourse.
      Independent associations between sexual debut and parental education and income
      were also found. Adolescents of fathers with higher education were less likely to
      report having had first sexual intercourse. A similar relationship was observed
      between mothers' levels of education and their sons. It was found that first
      sexual intercourse among 15- and 16-year-olds is associated with higher scores on
      body image concerns for adolescent girls. Social support and parental higher
      education seem to decrease the likelihood of having had first sexual intercourse
      in this age group. In future research, body image and various aspects of social
      support need to be better understood in relation to adolescent sexuality in
      various social and cultural contexts.

PMID- 19764281
TI  - The effect of spirituality and campus ministry on academic accomplishment in
      college students.
AB  - In this experiment the effect of spirituality and campus ministry involvement on
      academic accomplishment was studied. It was hypothesized that students who scored
      higher on the Index ofCore Spiritual Experiences, hereafter known as the
      INSPIRIT, taken from Measures of Religiosity (Hill, 1999), and who were more
      involved in campus ministry activities, would have higher grade point averages. A
      total of 247 Marist College sophomores and juniors were administered a
      questionnaire that contained the INSPIRIT and a list of campus ministry
      activities. The students were asked to fill out both sections and provide other
      information such as GPA, graduation year, and gender. Based on the replies, the
      researchers scored the INSPIRIT and rated the students involvement in campus
      ministry activities. The information was then entered into the computer and a
      correlation study was performed.

PMID- 19764282
TI  - Communal egg-laying in reptiles and amphibians: evolutionary patterns and
      hypotheses.
AB  - Communal egg-laying is widespread among animals, occurring in insects, mollusks,
      fish, amphibians, reptiles, and birds, just to name a few. While some benefits of
      communal egg-laying may be pervasive (e.g., it saves time and energy and may
      ensure the survival of mothers and their offspring), the remarkable diversity in
      the life histories of the animals that exhibit this behavior presents a great
      challenge to discovering any general explanation. Reptiles and amphibians offer
      ideal systems for investigating communal egg-laying because they generally lack
      parental care--a simplification that brings nest site choice behavior into sharp
      focus. We exhaustively reviewed the published literature for data on communal egg
      laying in reptiles and amphibians. Our analysis demonstrates that the behavior is
      much more common than previously recognized (occurring in 481 spp.), especially
      among lizards (N = 255 spp.), where the behavior has evolved multiple times. Our
      conceptual review strongly suggests that different forces may be driving the
      evolution and maintenance of communal egg-laying in different taxa. Using a game
      theory approach, we demonstrate how a stable equilibrium may occur between
      solitary and communal layers, thus allowing both strategies to co-exist in some
      populations, and we discuss factors that may influence these proportions. We
      conclude by outlining future research directions for determining the proximate
      and ultimate causes of communal egg-laying.

PMID- 19764283
TI  - Character displacement: ecological and reproductive responses to a common
      evolutionary problem.
AB  - Character displacement is the process by which traits evolve in response to
      selection to lessen resource competition or reproductive interactions between
      species. Although character displacement has long been viewed as an important
      mechanism for enabling closely related species to coexist, the causes and
      consequences of character displacement have not been fully explored. Moreover,
      character displacement in traits associated with resource use (ecological
      character displacement) has been largely studied independently of that in traits
      associated with reproduction (reproductive character displacement). In this
      review, we underscore the commonalities of these two forms of character
      displacement and discuss how they interact. We focus on the causes of character
      displacement and explore how character displacement can have downstream effects
      ranging from speciation to extinction. In short, understanding how organisms
      respond to competitive and reproductive interactions with heterospecifics offers
      key insights into the evolutionary causes and consequences of species coexistence
      and diversification.

PMID- 19764284
TI  - The value of self-assessment. Self-evaluation may be most important of all.

PMID- 19764285
TI  - Electronic health records.

PMID- 19764286
TI  - Telemedicine delivers healthy medical and financial benefits to ICUs.

PMID- 19764287
TI  - Models of physician engagement: an ambulatory strategy centered on choice, ease
      and access. Alexian Brothers Hospital Network redefines primary care.

PMID- 19764289
TI  - Strategic healthcare retail.

PMID- 19764288
TI  - Addressing compassion fatigue. The problem is not new, but it requires more
      urgent attention.

PMID- 19764290
TI  - Filling a dental void in rural Wisconsin.

PMID- 19764291
TI  - Fast pace of reform may leave providers behind. Contact with elected officials is
      imperative.

PMID- 19764292
TI  - Leading the multigenerational work force. A proactive approach will cultivate
      employee engagement and productivity.

PMID- 19764293
TI  - Governing in the new quality, safety landscape. For effective oversight, boards
      must engage at three levels: see, own and solve.

PMID- 19764294
TI  - Engaging the CFO in quality. Why it's a must and how to make it happen.

PMID- 19764295
TI  - Overcoming generational differences. Facilitated dialogue can build trust and
      enhance mutual understanding.

PMID- 19764296
TI  - What are your references saying?

PMID- 19764297
TI  - Recovering from recessionism: a passion to lead is required.

PMID- 19764299
TI  - Auditory induced bounce perception persists as the probability of a motion
      reversal is reduced.
AB  - When two identical targets move toward one another from opposite sides of a
      display and continue past one another along collinear trajectories, they can be
      perceived to either stream past or bounce off of one another. Streaming is the
      dominant perception in motion displays free of additional transients, while
      bouncing predominates when a transient (eg auditory or visual) is presented at
      the point of coincidence. We investigated whether the auditory induced bias
      towards bouncing would persist as the probability of a motion reversal was
      reduced by introducing a spatial offset either vertically in a 2-D display or in
      depth in a 3-D display. Offset conditions were combined with two auditory
      conditions (tone or no-tone at the point of coincidence) in the presence or
      absence of a central occluder. In conditions with no sound, streaming was
      reported on a clear majority of trials, regardless of spatial offset. When a
      transient tone was presented, reported motion reversals dominated and persisted
      for increasing verbal offsets up to 17.9 min of arc and for 3-D trajectory
      offsets up to 25.6 min of arc. The bounce-promoting effect of an auditory tone at
      the point of coincidence in stream/bounce displays persists in spite of rendering
      the visual motion sequence unambiguous and more consistent with streaming.

PMID- 19764300
TI  - Discriminating audiovisual speed: optimal integration of speed defaults to
      probability summation when component reliabilities diverge.
AB  - We investigated audiovisual speed perception to test the maximum-likelihood
      estimation (MLE) model of multisensory integration. According to MLE, audiovisual
      speed perception will be based on a weighted average of visual and auditory speed
      estimates, with each component weighted by its inverse variance, a statistically
      optimal combination that produces a fused estimate with minimised variance and
      thereby affords maximal discrimination. We use virtual auditory space to create
      ecologically valid auditory motion, together with visual apparent motion around
      an array of 63 LEDs. To degrade the usual dominance of vision over audition, we
      added positional jitter to the motion sequences, and also measured peripheral
      trajectories. Both factors degraded visual speed discrimination, while auditory
      speed perception was unaffected by trajectory location. In the bimodal
      conditions, a speed conflict was introduced (48 degrees versus 60 degrees s(-1))
      and two measures were taken: perceived audiovisual speed, and the precision
      (variability) of audiovisual speed discrimination. These measures showed only a
      weak tendency to follow MLE predictions. However, splitting the data into two
      groups based on whether the unimodal component weights were similar or disparate
      revealed interesting findings: similarly weighted components were integrated in a
      manner closely matching MLE predictions, while dissimilarity weighted components
      (greater than 3 : 1 difference) were integrated according to probability
      summation predictions. These results suggest that different multisensory
      integration strategies may be implemented depending on relative component
      reliabilities, with MLE integration vetoed when component weights are highly
      disparate.

PMID- 19764301
TI  - Kinaesthetic and visual perceptions of orientations.
AB  - In the present study we compare the kinaesthetic and visual perception of the
      vertical and horizontal orientations (subjective vertical and subjective
      horizontal) to determine whether the perception of cardinal orientations is
      amodal or modality-specific. The influence of methodological factors on the
      accuracy of perception is also investigated by varying the stimulus position as a
      function of its initial tilt (clockwise or counterclockwise) and its angle (22
      degrees, 45 degrees, 67 degrees, and 90 degrees) in respect to its physical
      orientation. Ten participants estimated the vertical and horizontal orientations
      by repositioning a rod in the kinaesthetic condition or two luminous points,
      forming a 'virtual line' in the visual condition. Results within the visual
      modality replicated previous findings by showing that estimation of the physical
      orientations is very accurate regardless of the initial position of the virtual
      line. In contrast, the perception of orientation with the kinaesthetic modality
      was less accurate and systematically influenced by the angle between the initial
      position of the rod and the required orientation. The findings question the
      assumption that the subjective vertical is derived from an internal
      representation of gravity and highlight the necessity of taking into account
      methodological factors in studies on subjective orientations.

PMID- 19764302
TI  - Anger and happiness are linked differently to the explicit detection of
      biological motion.
AB  - The detection of biological motion and the detection of emotion from this motion
      are important visual functions with obvious survival and social values. The
      perception of biological motion is remarkably robust, and numerous studies have
      shown that the emotional states of a person can be deduced from point-light
      biological motion. In the present study, we investigated the extent to which the
      detection of emotion from biological motion is linked to the explicit detection
      of human gait. Subjects performed gait detection and emotion detection for the
      same stimulus. The stimulus consisted of one coherent interval and one scrambled
      biological-motion interval, each of which contained one emotionally neutral and
      one emotional (angry or happy) walker. Significant correlations with gait
      detection performance were observed for anger detection but not necessarily for
      happiness detection, implying that the detection of anger may be more strongly
      linked to explicit gait detection. This leads to a hypothesis that differential
      dependence may reflect the differential behavioural meaning between anger and
      happiness detection; it may be more crucial to localise or identify a person with
      anger than happiness.

PMID- 19764303
TI  - Spatial distortions produced by purely dichoptic-based visual motion.
AB  - It is known that local, monocular motion (short-range motion) can produce local
      distortions of visual space. We wanted to know if local monocular motion was both
      sufficient and necessary for producing motion-based spatial distortions. We used
      a previously reported dichoptic motion stimulus in which the directional motion
      signal is not present in either eye's input but is only present after binocular
      combination. We show that such a stimulus can also induce perceived changes in
      spatial position. This suggests that local, monocular motion while being
      sufficient is not necessary for the production of motion-based illusions. It
      suggests that one source of motion signals responsible for this illusion is from
      binocular motion mechanisms.

PMID- 19764304
TI  - Controlled but independent: effects of mental rotation and developmental dyslexia
      in dual-task settings.
AB  - In two experiments, we compared the performance of normal-reading (n = 26) and
      dyslexic children (n = 22) in discriminating letters from their mirrored images.
      In experiment 1, they were always presented in the upright orientation; in
      experiment 2, they were presented in different angular orientations (0 degrees,
      90 degrees, 180 degrees). In order to determine whether task and dyslexia affect
      reaction times in early or late stages of processing, a dual-task paradigm was
      adopted in which the primary task was tone discrimination. Stimulus onset
      asynchrony (SOA) between first and second task was systematically varied (50 ms
      versus 400 ms). In both experiments dyslexics were slower overall than controls.
      No effects of mirror-image letters were found. In experiment 2, mental-rotation
      effects were additive with SOA. In accordance with earlier findings we concluded
      that the mental-rotation effect involves central processing capacity. Mental
      rotation effects were the same for normal-reading and dyslexic children; mental
      rotation is not impaired in dyslexia. Remarkably, SOA effects were larger in
      normal readers than in dyslexics. This result was explained by observing that
      dyslexics experience decision difficulties already on the first task. As a
      result, they do not benefit optimally from increased latencies between first and
      second tasks.

PMID- 19764305
TI  - Infants can't discriminate the orientation of a grating surrounded by an oblique
      square.
AB  - We examined whether infants could visually discriminate the orientation of a
      grating surrounded by an oblique square (experiment 1) and a vertical square
      (experiment 2). A familiarisation-novelty preference procedure was used. In
      experiment 1, infants aged 4 to 6 months did not visually distinguish the
      orientation of a grating surrounded by an oblique square. However, in experiment
      2, in which a vertical surrounding square was used, such infants visually
      distinguished the orientation of a grating. Our results suggest that the external
      visual frame can affect infants' perception of the orientation of a grating, as
      it does in adults. In experiment 1, a grating was within an oblique square. Here,
      the relative orientation with respect to the external visual frame differs from
      the orientation relative to the retinal/gravitational axes. Such discrepancy
      appears to cause confusion in infants' perception of orientation.

PMID- 19764306
TI  - Distortions of posterior visual space.
AB  - The study of spatial vision is a long and well traveled road (which, of course,
      converges to a vanishing point at the horizon). Its various distortions have been
      widely investigated empirically, and most concentrate, pragmatically, on the
      space anterior to the observer. The visual world behind the observer has received
      relatively less attention and it is this perspective the current experiments
      address. Our results show systematic perceptual distortions in the posterior
      visual world when viewed statically. Under static viewing conditions, observer's
      perceptual representation was consistently 'spread' in a hyperbolic fashion.
      Directions to distant, peripheral locations were consistently overestimated by
      about 11 degrees from the ground truth and this variability increased as the
      target was moved toward the center of the observer's back. The perceptual
      representation of posterior visual space is, no doubt, secondary to the more
      immediate needs of the anterior visual world. Still, it is important in some
      domains including certain sports, such as rowing, and in vehicular navigation.

PMID- 19764307
TI  - Interaction between reference frames during subjective vertical estimates in a
      tilted immersive virtual environment.
AB  - Numerous studies highlighted the influence of a tilted visual frame on the
      perception of the visual vertical ('rod-and-frame effect' or RFE). Here, we
      investigated whether this influence can be modified in a virtual immersive
      environment (CAVE-like) by the structure of the visual scene and by the
      adjustment mode allowing visual or visuo-kinaesthetic control (V and VK mode,
      respectively). The way this influence might dynamically evolve throughout the
      adjustment was also investigated in two groups of subjects with the head
      unrestrained or restrained upright. RFE observed in the immersive environment was
      qualitatively comparable to that obtained in a real display (portable rod-and
      frame test; Oltman 1968, Perceptual and Motor Skills 26 503-506). Moreover, RFE
      in the immersive environment appeared significantly influenced by the structure
      of the visual scene and by the adjustment mode: the more geometrical and
      meaningful 3-D features the visual scene contained, the greater the RFE. The RFE
      was also greater when the subjective vertical was assessed under visual control
      only, as compared to visuo-kinaesthetic control. Furthermore, the results showed
      a significant RFE increase throughout the adjustment, indicating that the
      influence of the visual scene upon subjective vertical might dynamically evolve
      over time. The latter effect was more pronounced for structured visual scenes and
      under visuo-kinaesthetic control. On the other hand, no difference was observed
      between the two groups of subjects having the head restrained or unrestrained.
      These results are discussed in terms of dynamic combination between coexisting
      reference frames for spatial orientation.

PMID- 19764308
TI  - A contextual effect of 2nd-order configural processing of non-face objects by non
      experts.
AB  - We investigated here the detection of 2nd-order configural relations both in
      faces and in non-face objects. In experiment 1 it was shown that observers were
      more sensitive to feature displacements in upright faces and houses than in
      inverted faces and houses. The presence of an inversion effect in the house
      stimuli suggested that 2nd-order relational processing was applied to the non
      face stimuli. In experiment 2, the inversion effect for houses was absent when
      only houses were presented. In experiment 3, face and house stimuli were once
      again presented in the same task and inversion effects were again seen for both
      types of stimuli. Together, these results suggest that 2nd-order relational
      processing can be flexibly applied to non-face objects when they are presented in
      the context of faces.

PMID- 19764309
TI  - Stereoscopic comparison as the long-lost secret to microscopically detailed
      illumination like the Book of Kells'.
AB  - The idea that the seventh- and eighth-century illuminators of the finest few
      Insular manuscripts had a working knowledge of stereoscopic images (otherwise an
      eighteenth- and nineteenth-century discovery) helps explain how they could create
      singularly intricate, microscopically detailed designs at least five centuries
      before the earliest known artificial lenses of even spectacle quality. An
      important clue to this long-standing problem is that interlace patterns drawn
      largely freehand in lines spaced as closely as several per millimeter repeat so
      exactly across whole pages that repetitions can be free-fused to form
      microscopically detailed stereoscopic images whose relief in some instances
      indicates precision unsurpassed in astronomical instruments until the
      Renaissance. Spacings between repetitions commonly harmonize closely enough with
      normal interpupillary distances that copying disparities can be magnified tens of
      times in the stereoscopic relief of the images. The proposed explanation: to copy
      a design, create a pattern, or perfect a design's template, the finest
      illuminators worked by successive approximation, using their presumably unaided
      eyes first as a camera lucida to fill a measured grid with multiple copies from a
      design, and then as a stereocomparator to detect and minimize disparities between
      repetitions by minimizing the relief of stereoscopic images, in the manner of a
      Howard-Dolman stereoacuity test done in reverse.

PMID- 19764310
TI  - Drawing the line: how people with autism copy line drawings of three-dimensional
      objects.
AB  - It is purported that the local perceptual style characteristic of those with
      autism results in them reproducing line drawings in a more localised manner than
      comparison individuals. Here we report an exception to this: the drawing
      strategies of those with autism were more global. When reproducing line drawings
      depicting three-dimensional objects, a sample of fifty-six participants with
      autism showed a greater tendency to begin by copying the two-dimensional outline
      of the figure than fifty-seven matched comparison participants (39.3% versus 8.8%
      of group; chi(1)2 = 14.46, p < 0.0005). We argue that this is consistent with the
      perception of those with autism being less conceptually driven, but not
      necessarily less global.

PMID- 19764311
TI  - The ultrasonic picture show and the politics of threatened life.
AB  - This article examines a local version of medical public discourse about fetal
      images produced through ultrasonography in Israel, where this technology has
      gained huge popularity. Nevertheless, I argue, ultrasound in Israel has not
      become engaged in the discursive production of "fetal subjects" central to the
      Euro-American life politics. Fetal images in Israel have become entangled in a
      "politics of threatened life": where "life" stands typically for the pregnant
      woman and "threat" for the fetus, while the prospect of a reproductive misfortune
      is the fabric through which pregnancies, regardless of their medical
      categorization as "low risk" or "high risk," are navigated and negotiated by
      doctors and women. The same processes of separation generated by ultrasonography
      forge different imagined relations between woman and fetus. This article opts to
      go beyond analyzing the cultural paradigms of thinking and the sociopolitical
      circumstances at play, to convey a sense of how notions of threatened life are
      produced.

PMID- 19764312
TI  - La tecnologia y las monjitas: constellations of authoritative knowledge at a
      religious birthing center in south Texas.
AB  - In this article, I contrast conceptualizations of authoritative knowledge in
      pregnancy and birth between U.S. midwives and their Mexican immigrant clients at
      a religious birthing center in south Texas. Although the two groups share certain
      orientations to pregnancy management, essential differences in prenatal care and
      birth epistemologies underscore distinct social and economic positions. I use
      narrative data to document and explain these differences, which throw into relief
      the hierarchies of identity and need that structure immigrant women's
      reproductive experiences. Unveiling the different epistemologies can also help to
      explain sometimes radically divergent ideas that have impacted the very
      survivability of the birthing center. By focusing on Mexican immigrant women's
      reproductive decision making in an alternative birthing center, this analysis
      responds to feminists' call to look to the margins to understand the diversity of
      women's responses to what Rapp and Ginsburg have called "stratified
      reproduction".

PMID- 19764313
TI  - Radical remedies: women, health, and the micropolitics of grassroots organizing
      in Mexico.
AB  - As states weaken and public health care deteriorates throughout the developing
      world, new spaces are opening for civil society groups to fill the gaps of
      declining health systems. In Mexico, popular health groups have responded to
      health care decline by building community clinics, establishing health promoter
      training programs, and opening natural medicine pharmacies. Lower- and working
      class women are the primary participants in these groups that use a self-help
      approach to find practical solutions to local health care problems. However,
      little is known about participants' circumstances, motivations, or the ideals
      they embrace. Drawing from women's narratives, I explore the "micropolitics" of
      women's participation in local health groups. I examine their efforts to reclaim
      control over the health process as a metaphor for claiming control over their
      lives. Highlighting the "instrumental effects" of participants' medical
      encounters and healing relationships, this case illuminates some unintended
      consequences of health care decline.

PMID- 19764314
TI  - Routes to government TB treatment: private providers, family support, and the
      process of TB treatment seeking among Ugandan women.
AB  - Tuberculosis (TB) remains a major source of morbidity and mortality in Uganda.
      This cross-sectional study explores Ugandan women's TB treatment-seeking
      processes to determine the routes to effective government TB treatment among a
      sample of urban, semirural, and rural women. This research focuses on women in
      particular as Ugandan women with tuberculosis must negotiate their treatment
      paths in a context where women tend to be politically and economically
      marginalized, with limited control of household resources and senior family
      members' health care decisions. The results examine the structural, social, and
      economic forces similarly guiding treatment seeking across the three research
      sites and then the specific differences among the settings. The findings suggest
      that the modest number of nongovernmental health care providers' diagnoses and
      referrals, particularly for urban and semirural participants, represents a
      critical barrier to biomedical TB treatment. Private providers' diagnosis delays
      also carry financial and physical costs, which undermine the resources available
      for subsequent TB treatment and participants' social and economic well-being.
      This study indicates that conceptualizations of the political economy of
      treatment seeking need to more fully acknowledge the dynamic nature of the
      microlevel political economic context of treatment seeking, including the domino
      social, economic, and health effects of structurally problematic health care
      systems.

PMID- 19764315
TI  - Community participation in New Mexico's behavioral health care reform.
AB  - In 2005, New Mexico implemented a unique reform in managed behavioral health
      services that seeks to ensure delivery of consumer-driven, recovery-oriented care
      to low-income individuals. Distinguishing features of the reform are the Local
      Collaboratives (LCs), regionally based community organizations designed by state
      government to represent behavioral health concerns of New Mexico's diverse
      cultural populations. We examine community response to the LCs, focusing on two
      broad sets of themes derived from 18 months of ethnographic fieldwork. The first
      set--structure and function--encompasses several issues: predominance of provider
      versus consumer voice; insufficient resources to support internal operations;
      imposition of state administrative demands; and perceived lack of state response
      to LC efforts. The second set--participation and collaboration--reveals how
      problems of information flow and other logistical factors impact involvement in
      LCs and how the construction of "community" introduced under this initiative
      exacerbates tensions across localities with varied histories and populations.

PMID- 19764316
TI  - Susto etiology and treatment according to Bolivian Trinitario people: a "masters
      of the animal species" phenomenon.
AB  - This article addresses two concepts that are quite widespread among Latin
      American cultures: susto or "'fright sickness," and the "masters of the animal
      species" philosophy, whereby individual animal spirits are believed to be "owned"
      by species-specific spiritual masters. This is the first article to integrate
      both these aspects, drawing from ethnographic data from the Trinitario people in
      Bolivia collected through participant-observation and semistructured
      ethnobotanical interviews on medicinal plants. Although Trinitarios have a long
      history of agriculture, their worldview is still partly one of animistic hunter
      and fisherman societies. This worldview is reflected in Trinitario susto etiology
      and treatment. Susto is locally believed to originate through soul theft by a
      variety of masters of the animal species and landscape spirits. Treatment is
      partly based on the principle of similia similibus curantur or "like cures like"
      and magicoritual ceremonies, but ethnopharmacological preparations are also well
      known and frequently used.

PMID- 19764317
TI  - The intensive medical care of sick, impaired, and preterm newborns in Israel and
      the production of vulnerable neonatal subjectivities.
AB  - Following reduction in mortality rates of term and preterm babies hospitalized in
      NICUs, neonataology refocused its concerns on the survivors' elevated risks of
      long-term health and developmental problems, thus turning the "intact survival"
      of hospitalized newborns into an equivalently desired moral and professional goal
      as their "survival." Based on ethnographic observations in an Israeli NICU
      ("pagia"), I suggest that the new moral practice has bearings on the construction
      of neonatal subjectivities. According to Jewish and Israeli laws, personhood is
      conferred on at birth. However, my findings indicate that in practice the
      question of "quality of life" often appears to be a stronger consideration than
      legal personhood when withdrawal of intensive therapies is discussed in the
      nursery. Consequently, the significance of the moment of birth to the
      construction of subjectivity is obscured. The construction of subjectivity as a
      progressively developed and irreversible category is challenged, and it becomes
      vulnerable.

PMID- 19764318
TI  - President, Society for Medical Anthropology speaking to the national health
      crisis: voices from medical anthropology.

PMID- 19764319
TI  - [Studies on grain filling characteristics in different spikes of triennium-growth
      Angelica sinensis].
AB  - OBJECTIVE: To study grain filling characteristics of triennium-growth Angelica
      sinensis in order to provide theoretic evidence for determining the adapted
      harvesting time for seeds. METHODS: 1000-grain fresh and dry weight, 100-grain
      volume, grain length, width and thickness in different spikes which were measured
      every day from the 8th day afte the head spike bloomed and finally estimated by
      Logistic equation. RESULTS: It was the peak filling time when the grain water
      decreased most rapidly. The grain filling speed, intensity, dry matter
      accumulation in head spike were all higher than those in the second spike, which
      resulted in early peak. The seeds in the head spike had advantages in grain
      filling and their adapted harvesting time should be the 13th day after blooming,
      when there were 86.2% of dry the maximum matter accumulation and 68.8% as water
      content in seeds. However, the adapted harvesting time for the seeds in the
      second spike should be the 14th day after the first spike bloomed, when there
      were 82.0% of the maximum dry matter accumulation and 72.2% as water content.
      CONCLUSION: According with the Logistic equation, the grains filling in different
      spikes had the same duration but differed in the intersity. We should harvest the
      whole plant seeds at a time, and away the head and below weak spikes before
      blooming.

PMID- 19764320
TI  - [Analysis of biochemical indices and efficient ingredients in autotetraploid of
      Dioscorea zingibiernsis].
AB  - OBJECTIVE: To improve the yield and quality of Dioscrea zingibiernsis. METHODS:
      The Biochemical indices and the diosgenin's content were analysed in the
      autotetraploid lines. RESULTS: The results showed that the activities of APX, SOD
      and POD in most of autotetraploid lines were higher than that in diploid line or
      close to it, there was also difference between autotetraploid lines and control
      lines in the SDS-PAGE of soluble proteins. The content of diosgenin in most
      autotetraploid plantlets were higher than that in the control. CONCLUSION: There
      were difference between autotetraploid and control lines in the content of
      diosgenin and Biochemical indices, therefore, inducing autotetraploid could be an
      effective way to breeding the superior varieties.

PMID- 19764321
TI  - [Study on purification and property of polysaccharide from Scolopendra
      subspinipes mutilans].
AB  - OBJECTIVE: To obtain polysaccharide from Scolopendra subspinipes mutilans and
      study its partial properties. METHODS: A raw polysaccharide was isolated from
      Chinese medicine Scolopendra subspinipes mutilans, and three groups were isolated
      by DEAE-52. The thin layer chromatography and gel filtration chromatography were
      used to detect the main monosaccharide composition and molecular weight of the
      group I. The inhibitory effect of the group I on tumor cells was detected by MTT
      assay. RESULTS: The molecular weight of the group I was 33.1 kD. The inhibitory
      effect of the group I on Hela cells was obvious, as its inhibitive rate was 60.8%
      on Hela cells when the polysaccharide's concentration was 3.13 microg/mL, but it
      had no effect on the Eca 109 cells. CONCLUSION: The group I has specific effects
      on different tumor cells.

PMID- 19764322
TI  - [Cloning and sequence analysis of full-length cDNA of secoisolariciresinol
      dehydrogenase of Dysosma versipellis].
AB  - OBJECTIVES: To obtain the full-length cDNA sequence of Secoisolariciresinol
      Dehydrogenase gene from Dysosma versipellis by RACE PCR,then investigate the
      character of Secoisolariciresinol Dehydrogenase gene. METHODS: The full-length
      cDNA sequence of Secoisolariciresinol Dehydrogenase gene was obtained by 3'-RACE
      and 5'-RACE from Dysosma versipellis. RESULTS: We first reported the full cDNA
      sequences of Secoisolariciresinol Dehydrogenase in Dysosma versipellis. The
      acquired gene was 991bp in full length, including 5' untranslated region of 42bp,
      3' untranslated region of 112bp with Poly (A). The open reading frame (ORF)
      encoding 278 amino acid with molecular weight 29253.3 Daltons and isolectric
      point 6.328. The gene accession nucleotide sequence number in GeneBank was
      EU573789. Semi-quantitative RT-PCR analysis revealed that the
      Secoisolariciresinol Dehydrogenase gene was highly expressed in stem. Alignment
      of the amino acid sequence of Secoisolariciresinol Dehydrogenase indicated there
      may be some significant amino acid sequence difference among different species.
      CONCLUSION: Obtain the full-length cDNA sequence of Secoisolariciresinol
      Dehydrogenase gene from Dysosma versipellis.

PMID- 19764323
TI  - [Studies on the HPLC fingerprint of Radix Codonopsis from different localities].
AB  - OBJECTIVE: To compare and analyze Radix Codonopsis from 18 different localities.
      METHODS: The HPLC was used to detect samples. MATLAB Software and the Computer
      Aided Similarity Evaluation was used to analyze the fingerprints. Similarity
      combined with principal component analysis (PCA) were used to compare and analyze
      Radix Condonopsis in different localities. RESULTS: It was found that processing
      drugs have effect on the quality of Radix Condonopsis and there are differences
      in species of Radix Codonopsis. CONCLUSION: This method could be used to compare
      and analyze the samples of Radix Codonopsis sources.

PMID- 19764324
TI  - [HPLC fingerprint of the antiarrhythmic fraction of Valeriana officinalis].
AB  - OBJECTIVE: To establish HPLC fingerprints of the Antiarrhythmic fraction of
      Valeriana officinalis. METHODS: Agilent C18 (250 mm x 4.6 mm, 5 microm) column
      was used and the acetonitrile-water was chosen as the mobile phase in a gradient
      mode. The column temperature was 380 degrees C and the detection wavelength was
      218 nm. The detection time was 70 min, and the flow rate was 1.0 mL/ min.
      RESULTS: Fifteen characteristic peaks were indicated in HPLC fingerprints. The
      relative retention time and the ranges of relative areas of the common peaks were
      also determined. CONCLUSION: This method is simple and accurate with a good
      reproducibility and provides a reference standard for the quality control of
      Valeriana officinalis.

PMID- 19764325
TI  - [HPLC fingerprint of flavonoids and phenols of Dendrobium nobile].
AB  - OBJECTIVE: To establish HPLC fingerprint of flavonoids and phenols of Dendrobium
      nobile. METHODS: Phenomenex prodigy ODS(3) C18 column (250 mm x 4.6 mm, 5 microm)
      was used with a mixture of acetonitrile-0.1% acetic acid as the mobile phase in a
      gradient mode, the column temperature was 25 degrees C, the flow rate was 1.0
      mL/min, and the detection wavelength was 254 nm. RESULTS: The flavonoids and
      phenols of Dendrobium nobile were well separated, and 10 fingerprint peaks in
      common were confirmed. CONCLUSION: This method is simple, accurate with good
      reproducibility, and can be used specifically for the quality control of
      Dendrobium nobile.

PMID- 19764326
TI  - [Studies on the chemical constituents of the stems of Piper betle].
AB  - OBJECTIVE: To study the chemical constituents from the stems of Piper betle.
      METHODS: Various chromatographic techniques were used to isolate and purify the
      constituents. The structures of these compounds were elucidated on the basis of
      spectral analysis. RESULTS: Nine compounds were isolated from the petroleum ester
      and ethyl acetate soluble fractions of the 70% acetone extract and their
      structures were identified as 6beta-hydroxystigmast-4-en-3-one (1), beta
      sitosterol (2), stigmasterol (3), oleanolic acid (4), 23-hydroxyursan-12-en-28
      oic acid (5), beta-sitosterol-3-O-beta-D-glucoside-6'-O-palmitate (6), beta
      daucosterol (7), (2S) -4'-hydroxy- 2,3-dihydroflavonone-7-O-beta-D-glucoside (8)
      and alpha-ethyl glucoside (9). CONCLUSION: Among these compounds, 1, 3 -9 are
      isolated from this plant for the first time.

PMID- 19764327
TI  - [Studies on the chemical constituents of the leaves of Polygonum multiflorum].
AB  - OBJECTIVE: To study the chemical constituents of the leaves of Polygonum
      multiflorum. METHODS: The chemical constituents were extracted with water and
      separated by manifold chromatography technique, and their structures were
      determined by spectral analysis. RESULTS: Eleven compounds were isolated and
      identified as physcion (I), emodin (II), noreugenin (III), apigenin (IV),
      hyperoside (V), rutin (VI), vitexin (VII), 2,3,5 ,4'-tetrahydroxy-stibene-2-O
      beta-D-glucoside (VIII), beta-amyrin (IX), beta-sitosterol (X), daucosterol( XI).
      CONCLUSION: Among these compounds, I - IV, VI - XI are isolated from the leaves
      of Polygonum multiflorum for the first time.

PMID- 19764328
TI  - [Analysis of monosaccharide compositions in Heterosmilax japonica polysaccharide
      by precolumn derivation HPLC].
AB  - OBJECTIVE: To establish precolumn derivation HPLC method to determine the
      monosaccharides in Heterosmilax japonica polysaccharide. METHODS: Heterosmilax
      japonica sample was hydrolyzed with trifluoroacetic (TFA)and derivated by 1
      phenyl-3-methyl-5-pyrazolone (PMP). The monosaccharide composition of
      Heterosmilax japonica polysaccharide was carried out by reversed-phase technique
      on a Kromasil C18 column with a mobile phase composed of 100 mmol/L ammonium
      acetate buffer (pH5.5) and acetonitrile in the ratio of 77: 23. The detection was
      carried out at 245 nm. RESULTS: The Heterosmilax japonica polysaccharide composed
      of mannose, rhamnose, glucose, galactose and xylose with amolar ratio of 66:
      1:7590: 452: 528. CONCLUSION: The HPLC method with precolumn derivatization is
      appropriate for the analysis of monosaccharide composition of Heterosmilax
      japonica polysaccharide and the method is simple, quick and accurate.

PMID- 19764329
TI  - [Study on the chemical constituents of the leaves of Ipomoea batatas].
AB  - OBJECTIVE: To study the chemical constituents of the leaves of Ipomoea batatas.
      METHODS: The constituents were isolated and purified by silica gel and TLC, and
      their structures were elucidated by spectroscopy. RESULTS: Six compounds were
      isolated from 90% ethanol extract and identified as tetracosane (I ), myristic
      acid (II), beta-sitosterol (II), beta-carotene (IV), daucosterol (V) and
      quercetin (VI). CONCLUSION: Compounds I, II, IV, V are isolated from this plant
      for the first time.

PMID- 19764330
TI  - [Study on proteomics of Jurkat cells treated with the extracts from Prunella
      vulgaris].
AB  - OBJECTIVE: To analyse the differential proteins of Jurkat cells after treated
      with the extracts from Prunella vulgaris using two-dimensional electrophoresis
      and mass spectrum. METHODS: Jurkat cell growth inhibitive effect of the extracts
      from Prunella vulgaris was analyzed by MTT assay. The total proteins of the cells
      were extracted after treated with the extracts in a dose of 20 microg/mL. Then 2D
      and MALDI-TOF-MS were used to assess the differential proteins. RESULTS: The
      extracts from Prunella vulgaris could depress the proliferation of Jurkat cells
      in a dose-dependent manner. After 2-DE and MALDI-TOF-MS,11 proteins were
      identified successfully, including glyceraldehyde-3-phosphate dehydrogenase,
      coagulation factor VII, Heterogeneous nuclear ribonucleoprotein L, heat shock 70
      kDa protein 8 isoform 2, immunoglobulin heavy chain variable region,
      heterogeneous nuclear ribonucleoprotein A2/B1, zinc finger protein 43, chaperonin
      containing TCP1, subunit 6A (zeta 1), isoform CRA_b, etc. CONCLUSION: The
      extracts from Prunella vulgaris could inhibit the growth of Jurkat cells
      significantly, and lead the proteomics change of Jurkat cells, which may be
      related to the anti-tumor effect of the extracts from Prunella vulgaris.

PMID- 19764331
TI  - [Effects of matrine on proliferation and telomerase activity of colon cancer
      SW1116 cells].
AB  - OBJECTIVE: To investigate the effects of matrine on proliferation and telomerase
      activity of colon cancer SW1116 cells. METHODS: The proliferation inhibitory rate
      was evaluated by MTT assay. The telomerase activity was analyzed by TRAP-ELISA,
      and the expression of hTERT mRNA was determined by semi-quantitative RT-PCR.
      RESULTS: Matrine displayed strong proliferation inhibitory effect in a dose-and
      time-dependent manner against SW1116 cells. Compared with control group, the
      telomerase activity and the expression of hTERT mRNA decreased significantly (P <
      0.05 or P < 0.01) in matrine group. CONCLUSION: Matrine can inhibit the
      telomerase activity by depressing the expression of hTERT in SW1116 cells and
      inhibiting cell proliferation.

PMID- 19764332
TI  - [Impacts of the formula of Suoquanwan(SQW) on expression of AQP-2 mRNA and AVPR
      V2 mRNA in the kidney of rat polyuria model of Yang-deficiency].
AB  - OBJECTIVE: To observe the impacts of the formula of Suoquanwan (SQW) on the
      expression of AQP-2 mRNA and AVPR-V2 mRNA in the kidney of rat polyuria model of
      Yang-deficiency. METHODS: The model rats were induced by adenine (250 mg/kg) for
      4 weeks, then treated respectively with SQW or dDAVP. The expression of AQP-2
      mRNA and AVPR-V2 mRNA in kidney of Yang-deficiency model by realtime fluorescence
      quantitative PCR method were investigated. RESULTS: In model rats, the expression
      of AQP-2 mRNA and AVPR-V2 mRNA in the kidney decreased, dDAVP and SQW high dose
      could increased the expression of AQP-2 mRNA and AVPR-V2 mRNA in the kidney. The
      others had no influence on the expression of AQP-2 mRNA and AVPR-V2 mRNA in the
      kidney. CONCLUSION: SQW can increase the expression of AQP-2 mRNA and AVPR-V2
      mRNA in the kidney of rat polyuria model of Yang-deficiency.

PMID- 19764333
TI  - [Anti-viral effects of Tankejing preparations against influenza virus A].
AB  - OBJECTIVE: To investigate the anti-viral effects of Tankejing preparations
      (including solutions, dry power inhalation and powder) against influenza virus A
      in vitro and the relationship between its anti-viral effect and preparations.
      METHODS: The inhibitive effect of different drug-added ways of Tankejing extracts
      against human influenza virus A (H3N2) in vitro were assayed by crystallized
      purple staining method with ribavirin as positive reference drug. Then we
      compared the anti-viral actions of different kinds of Tankejing preparations. At
      last, we carried on serum pharmacodynamics to test and verify the effect.
      RESULTS: Tankejing extracts had an effect on comprehensive inhibition and an
      inhibition on virus proliferation after adsorption. When the concentration was
      0.062 g/mL, the inhibition rate of solution dry power inhalation and powder were
      43.50%, 41.50% and 37.36%, respectively. The anti-viral effect of dry powder
      inhalation was better than power's in serum pharmacokinetis experiment.
      CONCLUSION: Tankejing preparations display an action against human influenza
      virus A in vitro. Those preparation with better solubility have greater anti
      viral effect.

PMID- 19764334
TI  - [The inhibitory effects of Realgar bioleaching solution on S180 ascites-tumor and
      its toxicity].
AB  - OBJECTIVE: To investigate the inhibitory effect of Realgar bioleaching solution
      (RBS) on tumor S180 cells line and estimate its toxicity, to provide experimental
      evidence for the further exploit of Realgar. METHODS: 24 hours after the models
      of ascites-tumor bearing mice were established, the mice were injected RBS once a
      day. The survival rates of S180 ascites-tumor bearing mice injected in RBS was
      studied, and the RBS acute toxicity of mice produced by oral, intraperitoneal or
      intravenous was evaluated by Drug Median Lethal Dose (LD50). RESULTS: The
      inhibitory effect of S180 cells in vivo had a dose-dependent manner. The survival
      rates of mice were 10% - 60% in the different dose in 15 days. The LD50 values of
      RBS by oral, intraperitoneal or intravenous were 5.27 mg/kg, 3.63 mg/kg and 2.68
      mg/kg, respectively. CONCLUSION: RBS has potent antitumor effect, LD50 value of
      RBS is lower than that of traditional medicine.

PMID- 19764335
TI  - [Effect of Wenyang Huazhuo Tongluo recipe contained serum on proliferation and
      cell cycle of systemic sclerosis skin fibroblasts].
AB  - OBJECTIVE: To investigate the effect of "Wenyang Huazhuo Tongluo recipe"
      (WYHZTLR) on proliferation and cell cycle of systemic sclerosis (SSc) skin
      fibroblasts in vitro by serum pharmacologic technique. METHODS: Prednisone, D
      penicillamine and WYHZTLR contained serum from patients with SSc were
      respectively added into cultured normal dermal fibroblast cell-line and SSc
      lesional dermal fibroblast cell-line. Then the cells were incubated for 48 hours.
      Cell proliferation and cell cycle were examined by methyl thiazolyl tetrazolium
      (MTT) assay and flow cytometry, respectively. RESULTS: Western medicine Chinese
      medicine and integrated Chinese and western medicine could markedly inhibit the
      proliferation of normal dermal fibroblasts and SSc lesional dermal fibroblasts in
      vitro compared with control group (P < 0.05 or P < 0.01). But 20% serum in
      integrated Chinese and western medicine group could markedly inhibit the
      proliferation of fibroblasts compared with western medicine group (P < 0.01).
      Different drug-contained serum of WYHZTLR could markedly increase the percentage
      of G0-G1 stage cells (P < 0.01) and depress the percentage of sphase cells and G2
      M stage cells compared with control group (P < 0.05 or P < 0.01). CONCLUSION:
      WYHZTLR can block the progression of SSc skin fibroblasts into sphase and G2-M
      stage and inhibit the proliferation of SSc skin fibroblasts, and WYHZTLR was
      unselectively interfered with normal and SSc fibroblasts in vitro.

PMID- 19764336
TI  - [Effect of TFCC on proliferation of the first trimester human cytotrophoblast and
      its possible signal transduction pathway].
AB  - OBJECTIVE: To investigate the effect of total flavones from Cuscuta chinens is
      (TFCC) on proliferation of the first trimester human cytotrophoblast and its
      possible signal transduction pathway. METHODS: The first trimester human
      trophoblast cells were isolated by trypsin/Dnasel digestion and discontinuous
      Percoll density gradient centrifugation. After identified by immunocytochemistry
      to Cytokeratin 7 and Vimentin, the trophoblast cells appared to more than 95%
      pure. MTT Assay was used to evaluate the effect of TFCC in vitro
      viability/proliferation of the first trimster human cytotrophoblasts, The PCNA
      expression of the first rimester human cytotrophoblasts were analyzed by the way
      of flow cytopmetry. The pERK level of the first trimester human cytotrophoblasts
      was analyzed by the way of western blotting. RESULTS: TFCC could promote
      viabilitylproliferation and PCNA expression of the first trimester human
      cytotrophobia in vitro, which could activate the ERK 1/2 in time-dependent and
      dosage-dependent manner.

PMID- 19764337
TI  - [Study on selecting the suitable solubilizing excipients for Shengmai injection].
AB  - OBJECTIVE: To select the suitable solubilizing excipients for Shengmai injection
      by the mean of hemolysis. METHODS: The hemolysis ratio of Shengmai injection,
      solubilizing excipients and different proportion of them were determined by
      absorption spectrometry. RESULTS: In the experimental concentration, Shengmai
      injection itself had no hemolytic effect. Polysorbate 80, Polyethylene glycol
      400, Polyethylene glycol 600, Poloxamer 188 solution had no hemolytic effect to
      appear, but all the experimental concentrations of Polysorbate 20 had hemolytic
      effect. When combining with different proportion of Polysorbate 20, Polyethylene
      glycol 400, Polyethylene glycol 600, Poloxamer 188 and Polysorbate 80 of high
      concentration (0.75% - 1%), Shengmai injection had hemolytic effect. CONCLUSIONS:
      The absorption spectrometry is more reliable for the judgement of hemolysis than
      macroscopic observation, and it is helpful to improve the accuracy to select the
      solubilizing excipients for the TCM injection. Polysorbate 80 can be used as
      solubilizing excipient of Shengmai injection, which is safe in the concentration
      range of 0.1% to 0.5%.

PMID- 19764338
TI  - [Optimal extraction of melampyrit from Euonymus fortunei by central composite
      design-response surface methodology].
AB  - OBJECTIVE: To optimize the process of extracting melampyrit from Euonymus
      fortunei by central composite design-response surface methodology. METHODS: The
      independent variables were the solvent fold and extractive time, and the
      dependent variable was the extraction rate of melampyrit from Euonymus fortunei.
      Then different mathematic models were used to estimate the relationship between
      the independent and dependent variables. The response surface methodology was
      used to optimize the process of extraction and the prediction was carried out
      through comparing the observed and predicted values. RESULTS: The regression
      coefficient of binomial fitting complex model was 0.9515, and the optimum
      conditions of extraction process were 12-fold volume of solvent, 1.5 hours for
      decoction and 2 times for extraction. The bias between the observed and predicted
      values was -5.37%. CONCLUSION: It shows that this method is convenient and the
      optimum model is highly predictive.

PMID- 19764339
TI  - [Simultaneous determination of anthraquinones in Liuwei'anxiao capsules by HPLC].
AB  - OBJECTIVE: To establish an RP-HPLC method for measuring the contents of aloe
      emodin, rhein, emodin, chrysophanol and physion in Liuwei'anxiao Capsules
      (traditional Chinese medicine). METHODS: The analysis was carried out with a
      Diamonsil-C18 column (200 mm x 4.6 mm, 5 microm) and a mobile phase of methanol
      0.05% phosphoric acid solution with gradient elution. The flow rate was 1.0
      mL/min and the column temperature was 35 degrees C. The detection wavelength was
      254 nm. RESULTS: The calibration curve was linear within the range of 1.622 -
      16.22 microg/mL (r1 = 0.9998), 0.6960 - 6.960 microg/mL (r2 = 0.9998), 2.448 -
      24.48 microg/mL (r3 = 0.9995), 2.752 - 27.52 microg/mL (r4 = 0.9997), 2.702 
      27.02 microg/mL (r = 0.9997) for aloe-emodin, rhein, emodin, chrysophanol and
      physion, respectively. CONCLUSION: This method is convenient, accurate and
      reproducible for the quality control of Liuwei'anxiao Capsules.

PMID- 19764340
TI  - Alteration of nitric oxide gas on gene expression of endothelin-1 and endothelial
      nitric oxide synthase by a time- and dose-dependent manner in human endothelial
      cells.
AB  - Our purpose was to investigate the gene expression of endothelin-1 (ET-1) and
      endothelial nitric oxide synthase (eNOS) in human umbilical vein endothelial
      cells (HUVECs) under various concentrations and periods of exogenous nitric oxide
      (NO) gas exposure. Cultured HUVECs were exposed to 0, 20, and 80 ppm NO for 0,
      24, and 48 h. With NO exposure for 24 h, ET-1 peptide levels decreased in both
      the 20 and 80 ppm groups. Thereafter, at 48 h, ET-1 peptide levels persistently
      decreased in the 20 ppm group, but significantly increased in the 80 ppm group.
      Furthermore, there was a significant decrease in the expression levels of eNOS
      protein and mRNA in the 80 ppm 48 h group. The data suggest a time- and dose
      dependent effect of NO gas exposure on the gene expression of ET-1 and eNOS in
      HUVECs. A high concentration and long period of NO exposure induces an inhibition
      of eNOS and enhancement of ET-1, which could lead to vasoconstriction. These
      findings may have clinical implications in NO therapy regarding the optimal dose
      and period.

PMID- 19764341
TI  - Importance of cyclooxygenase 2-mediated low-grade inflammation in the development
      of fructose-induced insulin resistance in rats.
AB  - This study was designed to examine the role of cyclooxygenase (COX) 2-mediated
      low-grade inflammation in the development of fructose-induced whole body and
      muscular insulin resistance in rats. The rats were on regular or fructose
      enriched diets for 8 weeks. Fructose-fed rats were further divided into 3 groups
      (n = 8 per group). There were fructose-fed rats, fructose-fed rats with
      nimesulide (a selective COX2 inhibitor, 30 mg/kg/day, gavage) and fructose-fed
      rats with celecoxib (a selective COX2 inhibitor, 30 mg/kg/day, gavage). The
      present result showed that fructose-induced time-dependent increases in systolic
      blood pressure and fasting plasma insulin and triglyceride levels were
      significantly suppressed in rats treated with nimesulide or cerecoxib. The ratio
      of area under glucose curve divided by area under insulin curve obtained during
      the oral glucose tolerance test was significantly decreased in fructose-fed rats,
      which were markedly reversed in those co-treated with nimesulide or celecoxib.
      Accordingly, fructose-induced decrease in insulin-stimulated glucose uptake in
      soleus muscle was significantly reversed in those combined with nimesulide or
      celecoxib. Fructose-induced time-dependent increases in plasma 8-isoprostane and
      PGE metabolites were concomitantly suppressed by nimesulide or celecoxib co
      treatment. The present study demonstrates that the COX2-mediated low-grade
      inflammation, especially mediated by increase in oxidative stress was important
      in the development of insulin resistance in fructose-fed rats.

PMID- 19764342
TI  - The cooperative phenomenon of autonomic nervous system in urine storage for
      Wistar rats.
AB  - The fractal dimension (FD) and spectral frequencies of physiological signals are
      two important indices in the study of physiological functions and dynamical
      diseases. The first index can be used to characterize the intensity and the
      second the rhythms of signals embedded in seemingly random data. Recent studies
      using both indices verified that synergic co-activations of bladder and external
      urethral sphincter (EUS) of Wistar rats were present during the voiding of urine.
      In this study, the primary aims were to (1) examine if the involved muscles in
      the lower urinary tract would be under similar coactivations during the urine
      storage phase, and (2) characterize quantitatively the sympathetic and
      parasympathetic nerve activities simultaneously. Eighteen experiments were
      performed on six intact adult female Wistar rats and then the electromyogram of
      EUS and cystometrogram of bladder were analyzed. Results indicated that the EUS
      did not contain any significant spectral frequencies in the storage phase.
      Furthermore, its FDs (1.5918 +/- 0.0157) indicated that no appreciable amount of
      signal intensities was observed in the EUS. On the other hand, the bladder
      exhibited parasympathetic frequency of 8 Hz with signal-to-noise ratio (SNR) =
      19.9001 decibel (dB) for group mean, and sympathetic frequency of 19 Hz with SNR
      = 22.8330 dB for group mean. In addition, its FDs (1.4796 +/- 0.0092) indicated
      relatively persistent intensities during storage, as compared to that of EUS
      (1.5918 +/- 0.0157) with statistical significance (P < 0.01). We concluded that
      the EUS was not activated during the phase of storage. The bladder was under the
      cooperative, not antagonistic, sympathetic and parasympathetic nerve activities
      with discernible rhythmic frequencies and persistent intensities.

PMID- 19764343
TI  - Dynamic performance evaluation on the synergy of micturition in spinal cord
      injured female rats under pharmacological effects.
AB  - Recently, a temporal "coherent" fractal structure and synchronization of rhythms
      were proposed as two essential indicators for efficient voiding during
      micturition in female rats. The former was correlated with the intensity and the
      latter the frequency of physiological signals embedded in random noise. Studies
      using both indices confirmed that synergic co-activations of bladder and external
      urethral sphincter (EUS) of female rats were present during the voiding of urine.
      Therefore, it would be interesting to investigate if these two criteria could be
      used in the performance evaluation of pharmacological effects on spinal cord
      injured rats during micturition. In this paper, the primary goals were to (1)
      examine if the involved muscles in the lower urinary tract would be under similar
      synergic co-activations during the administration of capsaicin (CAP) and
      resiniferatoxin (RTX), and (2) characterize quantitatively the differences of
      their nervous responses simultaneously. A total of 62 micturition experiments
      were performed on sixteen spinal cord-injured adult female Sprague-Dawley rats,
      and then the electromyograms of EUS and cystometrograms of bladder were analyzed.
      Results based on the aforementioned criteria indicated that the synergy of
      bladder and EUS during micturition by using RTX was better than that of the CAP.
      Furthermore, the residue urine volumes for rats under the former treatment were
      smaller than those of the rats under the latter treatment. Consequently, we
      concluded that the administration of RTX was more effective than CAP in
      facilitating voiding in the spinal cord-injured rats.

PMID- 19764344
TI  - Association of increased pain threshold by noise with central opioid neurons.
AB  - Several studies indicated that stress would induce analgesia. Noise, one of the
      stressors, was assumed to be one of the elements to enhance the threshold of pain
      tolerance. Since noise might affect human's daily life, it is important to know
      the mechanism underlying this phenomenon. The objective of this study was to
      explore the possible mechanism which was trying to explain how the noise affects
      central nervous system and the possible relationship between this effect and the
      involvement of opioid neurons. In the preliminary study, the analgesic effect was
      corroborated in ICR mice in a formalin study. The results are as follows: [1]
      Naloxone (a micro-opioid receptor antagonist; 1 mg/kg, i.p.), beta-FNA (a delta
      opioid receptor antagonist; 5, 10 mg, i.c.v.) and naltrindole (a delta-opioid
      receptor antagonist; 1, 5 mg/kg, i.p.) were found to reduce antinociceptive
      effect. [2] nor-BNI (a kappa-antagonist; 1 microg, i.c.v.) had much effect on
      noise induced analgesic. In conclusion, this study suggests that noise stress
      enhanced the threshold of analgesia, which might be related to micro- and delta
      opioid receptors in the central nervous system.

PMID- 19764345
TI  - Relaxing effects of phytoestrogen alpha-zearalanol on rat thoracic aorta rings in
      vitro.
AB  - The aim of this research is to investigate the vasorelaxing effects and
      mechanisms involved in the phytoestrogen alpha-zearalanol (alpha-ZAL) in rat
      thoracic aortas rings. Intact or endothelium denuded rat thoracic aortas rings
      were put in individual organ chamber to observe the endothelium-dependent or
      independent vasorelaxing effects of alpha-ZAL (10(-10)-10(-5) M). The thoracic
      aortas rings were pre-contracted with phenylephrine. The relaxing effects of
      alpha-ZAL were observed and the influence of N(omega)-nitro-L-arginine
      methylester (L-NAME, NOS inhibitor), methylene blue (MB, guanylate cyclase
      inhibitor), charybdotoxin (ChTX, Ca(2+)-activated K+ channel blocker),
      glibenclamide (ATP-sensitive K+ channel blocker), (-) BayK8644 (L-type Ca2+
      channel agonist) and ICI182,780 (estrogen receptor antagonist) were pre-incubated
      with alpha-ZAL, respectively, to explore the possible mechanisms involved in this
      vasorelaxation. Furthermore, the Phospho-eNOS expression and cGMP level in the
      aortas tissue were detected by Western blot and radioimmunity, respectively; the
      NO level in perfusate was assaied by chromatometry. Our result showed that alpha
      ZAL (10(-10)-10(-5) M) induced both endothelium-dependent and -independent
      relaxation of rat thoracic aortas rings. The vasorelaxing effects of alpha-ZAL
      were dose-dependent whether the endothelium was intact or not. In endothelium
      intact aortas rings, alpha-ZAL-induced vasorelaxation might be inhibited by L
      NAME, MB, charybdotoxin, glibenclamide and (-) BayK8644, but not ICI182,780. (-)
      BayK8644 could also inhibit alpha-ZAL-induced vasorelaxation in endothelium
      denuded aortas rings.10(-7)-10(-5) M alpha-ZAL might induce the Phospho-eNOS
      expression in thoracic aorta tissue, increase the NO level in perfusate and cGMP
      content in thoracic aorta tissue. Meanwhile, L-NAME might decrease both NO and
      its downstream cGMP level. Methylene blue might decrease the level of cGMP. These
      results suggest that alpha-ZAL induces a partly endothelium-dependent relaxation
      of rat thoracic aortas rings; the possible mechanisms involved in this rapid
      vasorelaxation include activation of eNOS/NO/cGMP pathway, opening of VSMCs ATP
      sensitive and Ca(2+)-activated K+ channels through secretion of EDHF from
      endothelium. Furthermore, this relaxation also appears to be mediated by both
      direct and indirect inhibition of voltage-dependent Ca2+ channel of VSMCs, while
      it is not concerned with activation of estrogen receptor.

PMID- 19764346
TI  - Influence of intermittent hypobaric exposure on SOD and TBARS levels in trained
      rats.
AB  - Live high train low (LHTL) is a well-known training model for preparation of
      competitions. In this study, the thiobarbituric acid reacting substances (TBARS)
      levels and superoxide dismutase (SOD) activity were determined in heart, lung and
      muscle tissues of rats. They were intermittently exposed to hypobaric pressure of
      523 mmHg, corresponding to an altitude of 3,000 m, and they performed swim
      training at sea level. Two groups of male rats were trained to swim for thirty
      minutes a day and 4 days a week, lasting 9 weeks. Two groups were exposed to
      hypobaria for 120 min a day and 4 days a week for 9 weeks in pressure cabin. In
      heart tissue, TBARS levels of normobaric trained (NbT) group was higher (P <
      0.05) than those of the normobaric sedentary (control) group. TBARS levels of
      hypobaric trained (HbT) group was higher than those of the control and hypobaric
      sedentary (Hb) groups (P < 0.001; P < 0.01, respectively). TBARS levels of lung
      tissue of HbT group was also higher than those of the same groups (control; P <
      0.01, Hb; P < 0.05, respectively). In muscle tissue, TBARS levels of HbT group
      was higher than those of the sedentary groups (control; P < 0.001, Hb; P < 0.05,
      respectively). SOD activity of heart tissue of HbT group was higher (P < 0.001)
      than that of the other groups. In lung tissue, SOD activity of control group was
      lower than that of the other groups (HbT; P < 0.001, NbT; P < 0.01, Hb; P < 0.01,
      respectively). In muscle tissue, SOD activity of HbT group was higher (P < 0.01)
      than that of the control group. The results of this study suggest that
      intermittent hypobaric exposure may augment exercise-induced oxidative stress in
      heart, lung and muscle of trained rats.

PMID- 19764347
TI  - Effects of acupuncture at Neiguan (PC 6) on electroencephalogram.
AB  - The aim of this study was to investigate if there were any effects on the
      electroencephalogram (EEG) of human brain by the manual stimulation of Neiguan
      (PC 6) acupuncture site. In this paper, two groups of six healthy male volunteers
      of ages 27.6 +/- 14.2 (mean +/- SD) and 28.5 +/- 13.0 (mean +/- SD) and no
      neurological disease participated in this study. A digital storage of 12-channel
      EEG recorder was used and spectral analyses of the data set of 18 trials were
      obtained before, during, and after sham/ manual acupuncture. To minimize
      artefacts, all data were collected with the subjects alert but eyes closed. No
      significant changes (P > 0.05) were obtained for the sham acupuncture group. As
      for the manual acupuncture group, the needle was inserted perpendicularly into
      the PC 6 acupuncture site and manually stimulated about 15 to 30 seconds to
      achieve De Qi sensation. Needles were left in place for 30 min and then removed.
      Analysis of the EEG data due to acupuncture was compared to the baseline data and
      changes were obtained. First, all trials had an increase in the amplitude and
      power of the alpha band during manual acupuncture (P < 0.05) when compared with
      the baseline data. Secondly, in the mean time, the frequency peaks in alpha band
      of 12-channels were all synchronized with much smaller standard deviation (P <
      0.01). Thirdly, the manual acupuncture effects of higher power and synchronized
      frequencies persisted for at least 10 minutes after the experiment (P < 0.05) and
      did not disappear immediately for all 18 experiments. Finally, we hypothesized
      that the higher power and synchronized rhythms in brain oscillations may have to
      do with autonomic nervous system.

PMID- 19764348
TI  - Neural reflex hypotension induced by very small dose of hypertonic NaCl solution
      in rats.
AB  - Although the precise mechanisms of transient hypotension after intravenous
      infusion of hypertonic saline (HTS) are not yet clarified, a rapid infusion of
      HTS is widely used as the initial therapy of hypovolemia. We investigated the
      effect of the intravenous infusion of a small dose of 0.97-9.7% NaCl solutions in
      anesthetized rats. Intravenous infusion of HTS at a rate of 0.3 ml/kg/min for 1
      min produced the transient hypotension lasting for several minutes. The depressor
      response to HTS was not abolished by bilateral cervical vagotomy. The HTS
      infusion into the femoral vein evoked the depressor response with a larger
      magnitude and a shorter latency than that into the aortic arch. While the
      arterial baroreceptor pressure was kept constant at the baseline level of
      systemic arterial pressure, HTS-induced hypotension was significantly augmented.
      The gain factor of the arterial baroreflex was reduced by intravenous HTS.
      Pretreatment with bretylium tosylate completely abolished the depressor response
      without affecting the baseline level of arterial pressure. These results suggest
      that the depressor response to the very small dose of intravenous HTS is the
      sympathosympathetic neural reflex with cardiopulmonary afferents and vasomotor
      efferents.

PMID- 19764349
TI  - Vulnerability to unidirectional conduction block and reentry in rabbit left
      ventricular wedge preparation: effects of stimulation sequence and location.
AB  - Many factors influence the initiation of unidirectional conduction block and
      reentry. To explore the influential factors on the temporal vulnerable window of
      the unidirectional conduction block, we investigated the effect of stimulation
      sequence and location on the temporal vulnerability in epicardial and endocardial
      sites in an arterially perfused rabbit left ventricular wedge preparation at
      three basic cycle lengths (BCL) of 2,000, 1,000 and 500 ms. An extrastimulus (S2)
      was introduced at coupling intervals incremented by 1 ms to scan the entire
      diastolic interval. The results showed that the vulnerable window increased with
      the lengthening of BCL, which ranged from 48.55 +/- 18.04 ms at BCL of 500 ms to
      92.50 +/- 25.59 ms at BCL of 2,000 ms for endocardial, and is a similar style for
      epicardial from 21.00 +/- 14.02 ms at BCL of 500 ms to 75.71 +/- 16.34 ms at BCL
      of 2,000 ms (P < 0.05). The vulnerable window of endocardial was wider than that
      of epicardial (P < 0.05). Furthermore, the window size for reentry was about 39%
      smaller than that for unidirectional conduction block. Meanwhile, we found that
      increasing the number of premature beats enlarged the vulnerable window markedly
      due to enhanced transmural dispersion of repolarization (TDR) of ventricle. The
      vulnerable window is an effective index to evaluate the increased risk for
      unidirectional conduction block. Therefore, the factors that increase the
      vulnerable window are associated with the higher incidence of ventricular
      arrhythmias.

PMID- 19764350
TI  - The role of Cdk5 in retinoic acid-induced apoptosis of cervical cancer cell line.
AB  - Cdk5 is a small serine/threonine protein kinase which belongs to Cdk family.
      Unlike other Cdk members, so far Cdk5 is known to be irrelevant in cell cycle.
      Cdk5 kinase activity is regulated by binding with its activator, p35. Our
      previous results indicate that CdkS and p35 are involved in drugs-induced
      apoptosis of prostate cancer cells. Retinoic acid (RA) is one of the vitamin A
      related compounds. Because of its potency on biological functions, it has been
      widely studied in its novel actions including the ability to inhibit cancer cell
      growth and to induce apoptosis. Here, we report that RA treatment decreased the
      growth of human cervical cancer cell line, HeLa, and Cdk5 contributed to this
      effect. The involvement of Cdk5 in RA-reduced cell survival was performed by
      treatments of Cdk5 inhibitor and siRNA. We further identified that RA-induced
      growth inhibition was partly correlated to Cdk5 activity-related apoptosis by
      detecting cell cycle distribution of sub G1 phase and the signals of Annexin V
      staining. In addition, our results also indicated that Cdk5 activity was involved
      in RA-induced HeLa apoptosis by detecting cleavages of caspase-3 and its
      substrate, PARP (poly (ADP-ribose) polymerases) Interestingly, the nuclear
      localizations of Cdk5 and p35 proteins were increased by RA treatment, which,
      again, suggests the involvement of Cdk5 and p35 in RA-induced apoptotic effects.
      In conclusion, we provide evidence to suggest that Cdk5 and p35 might play
      important roles in RA-induced HeLa apoptosis.

PMID- 19764351
TI  - Enhancement of AG1024-induced H9c2 cardiomyoblast cell apoptosis via the
      interaction of IGF2R with Galpha proteins and its downstream PKA and PLC-beta
      modulators by IGF-II.
AB  - Our previous studies found that insulin-like growth factor-I receptor (IGF1R)
      signaling blockade caused cardiac hypertrophy, and that apoptosis is required for
      upregulating the IGF-II and the IGF-II/ mannose 6-phosphate receptor (IGF2R)
      gene. However, the role of IGF-II in the regulation of cell apoptosis through
      IGF2R is little known. In this study, we hypothesized that IGF-II may induce cell
      apoptosis through IGF2R but is dependent on IGF1R activity. Western blots and
      TUNEL assay revealed that in the presence of IGF1R, exogenous IGF-II acts, like
      IGF-I, would increase phospho-Akt through IGF1R, but does not affect the caspase
      3 activation and apoptotic induction in H9c2 cardiomyoblast cells. Conversely,
      AG1024, an inhibitor of IGF1R activity, causes cell apoptosis, and the treatment
      with IGF-II further enhances this process, implying that it occurs through IGF2R.
      Moreover, immunoprecipitation assay revealed that treatment with IGF-II could
      enhance the interaction of IGF2R with Galphai and Galphaq but reduce its binding
      with Galphas, resulting in the reduction of phospho-PKA and the activation of PLC
      beta. Taken together, these data provide new insight into the dual role of IGF-II
      in the control of IGF1R dependent cell apoptosis and involved activation of IGF2R
      signaling. Improving IGF1R activity and suppressing IGF2R may be a good strategy
      to prevent the progression of heart disease with cardiomyocyte apoptosis.

PMID- 19764352
TI  - Involvement of GABA-mediated inhibition in shaping the frequency selectivity of
      neurons in the inferior colliculus of the big brown bat, Eptesicus fuscus.
AB  - In central auditory signal processing, neural inhibition plays an important role
      in sharpening the selectivity of auditory neurons. The present study examines the
      involvement of GABA-mediated inhibition in shaping the frequency selectivity of
      neurons in the bat inferior colliculus (IC) using forward masking paradigm and
      bicuculline application. At each study session, we recorded two IC neurons with a
      pair of electrodes and reciprocally studied whether a sound that served as a
      probe to elicit response of one neuron might serve as a masker to affect the
      frequency tuning curve (FTC) of the other paired neuron. Among the 33 pairs of IC
      neurons recorded, this forward masking paradigm produces sharpening of the FTC in
      29 (88%) pairs of IC neurons and broadening of the FTC in 4 (12%) pairs of IC
      neurons. The degree of sharpening of FTC decreases with recording depth as well
      as with the difference in the best frequency and recording depth between each
      pair of IC neurons. Although bicuculline application broadens the FTC of all IC
      neurons, forward masking still produces sharpening of the FTC in most IC neurons.
      These data suggest that population of IC neurons are highly correlated during
      frequency analysis such that frequency selectivity of some groups of IC neurons
      is improved through inhibition while the spectrum of frequency sensitivity of
      other groups of IC neurons is enhanced through excitation. Biological
      significance of these data relevant to acoustic signal processing is discussed.

PMID- 19764353
TI  - Decrease of heatstroke-induced multiorgan dysfunction by whole body cooling in
      streptozotocin-induced diabetic rats.
AB  - The present study was conducted to assess the effects of whole body cooling on
      multiorgan dysfunction that occurred during heatstroke in streptozotocin (STZ)
      induced diabetic rats. The rats were randomly divided into four groups: [1] the
      normal control, [2] diabetic control, [3] diabetic heatstroke, and [4] diabetic
      heatstroke-whole body cooling (WBC). They were exposed to ambient temperature of
      43 degrees C for exactly 58 min to induce heatstroke. When the diabetic
      heatstroke rats underwent heat stress, their survival time values were found to
      be 11-13 min. Immediately after the onset of heatstroke, resuscitation with body
      cooling greatly improved survival (221-257 min). Compared with the diabetic (STZ
      treated) controls, the diabetic-heatstroke rats displayed higher levels of body
      temperature, intracranial pressure, serum nitric oxide metabolite, tumor necrosis
      factor-alpha and dihydroxybenzoic acid, blood urea nitrogen, creatinine, alanine
      aminotransferase, aspartate aminotransferase, and alkaline phosphatase. In
      contrast, the values of mean arterial pressure, cerebral perfusion pressure, and
      brain levels of local blood flow, and partial pressure of oxygen were all
      significantly lower during heatstroke. The cerebrovascular, renal, and hepatic
      dysfunction, the increased levels of nitric oxide metabolites, tumor necrosis
      factor-alpha, and dihydroxybenzoic acid in the serum during heatstroke were
      significantly reduced by WBC. Although the serum interleukin-10 maintained at a
      negligible levels before heat stress, they were significantly elevated by WBC in
      diabetic-heatstroke rats. The data demonstrate that heatstroke-induced multiorgan
      dysfunction in streptozotocin-induced diabetic rats can be decreased by WBC.

PMID- 19764354
TI  - [Death of pedestrians after trafic accidents with motor cars].
AB  - It was analyzed 431 cases of pedestrians hit by cars who died during years 1996
      2005 and their body was examined in the Institute of Forensic Medicine in Brno.
      In the study there were observed factors of traffic accident, time of the
      accidents, day in the week, production mark of the car, time of surviving of
      pedestrians, type of the hit, severity of the injury and cause of the death. The
      results of laboratory examination of ethylalcohol and drugs were studied. The
      statistical results were discussed and compared with the literature. The most
      frequent age category were persons 71-80 years old. The most frequent day of
      traffic accident were Wednesday and Friday and in the evening. The most frequent
      period of year were months since November till January. The less accidents
      happened during the summer. The most accidents were localized on municipal roads,
      the less on highways. There was observed the significant accumulation of
      accidents on crosswalks after changing of traffic rules from the year 2001. No
      drugs were found by the victims but the occurrence of ethylalcohol was very high.
      In the laboratory examinations was ethylalcohol positively tested in 70 percents
      by men and 25 percents by women. The most frequent category was heavy
      drunkenness. The most frequent type of a hit was the one from lateral direction,
      the second was behind hits and the third from the head-on direction. The other
      types of the hit including crossing were found in eight percents. The numbers of
      injuries of the parts of the body by various types of the hit were examinated by
      statistical methods.

PMID- 19764355
TI  - [Problems on Czech anatomical nomenclature in forensic medicine].
AB  - The paper describes the medico-legal language style of texts which are often
      meant for non-medical scholars. Traditionally, the Czech language has been used
      in forensic medicine, instead of Latin (words with Latin roots). The paper also
      presents requirements for the language style of medico-legal texts as we have
      found them in academic publications. The core of the paper is an analysis of the
      anatomical terms extracted from autopsy protocols. We focus on designation of
      those anatomical structures which do not have their established Czech
      equivalents. Possibilities of a future research of the Czech anatomical
      nomenclature standardization for speech recognition (e.g., autopsy protocols) are
      mentioned.

PMID- 19764356
TI  - Diagnostics of fatal hydrogen sulfide poisonings.
AB  - INTRODUCTION: Cases of fatal hydrogen sulfide poisonings are rarely presented in
      forensic medicine practice. They mostly occur in occupational settings and
      occasionally are mass. Due to occupational poisonings caused by gases, hydrogen
      sulfide is ranked second regarding frequency-dependent incidence. Hydrogen
      sulfide at high concentrations is undetectable to human senses resulting in
      increased risk of fatal poisoning. Such poisonings represent a particular group
      with respect to their objectification by toxicological analysis. AIM: The aim of
      this paper is to demonstrate possibilities of laboratory diagnostics of fatal
      hydrogen sulfide poisonings. PATIENTS AND METHODS: The paper provides a
      retrospective overview of 15 cases of fatal hydrogen sulfide poisonings which
      occurred in the history of the Institute of Forensic Medicine of the School of
      Medicine, Comenius University in Bratislava. All cases were completely analysed
      by morphological and toxicological methods. The samples of blood and pulmonary
      tissue were examined in the toxicological analysis. The method of analysis of
      alveolar air was developed by Bauer. An experiment for detection of post-mortem
      production of hydrogen sulfide in the body was performed. RESULTS: Morphological
      findings in all autopsied and analysed cases were similar and nonspecific for
      poisoning diagnosis. A significant change in possibilities of toxicological
      analysis occurred in 1968. Since then a direct identification of toxic gas
      through the analysis of alveolar air has been possible. CONCLUSION: Taking into
      consideration summarization and comparison of the analysis results of the cases
      from archive materials of the authors, it is possible to claim that at the
      workplace in Bratislava a unique objective method of proving this gaseous poison
      in biological material used so far has been developed. Some negative or
      unconvincing results of toxicological analysis again refer to pitfalls of
      diagnostics of hydrogen sulfide poisonings, which must be complex and based upon
      an efficient collaboration particularly between a medical examiner and
      toxicologist-analyst together with other bodies complementing the required
      spectrum of investigated circumstances and clinical data.

PMID- 19764357
TI  - It's Twitter time.

PMID- 19764358
TI  - Security. Raising red flags: new rules require protection against identity theft.

PMID- 19764359
TI  - Finance. Restrictions eased on federal mortgage insurance program.

PMID- 19764360
TI  - Energetic about improving quality. Interview by Matthew Weinstock.

PMID- 19764361
TI  - Emergency department. For kids only: pediatric EDs on the rise.

PMID- 19764362
TI  - Marketing. Economy puts marketing budgets in a bind.

PMID- 19764363
TI  - Risk and reform.

PMID- 19764364
TI  - A model of efficiency.
AB  - Could your hospital survive on Medicare payments alone? That's a question some of
      the nation's leading health care systems are asking as they take a hard look at
      their operations and brace for tighter reimbursements from both public and
      private payers. Novant Health, for example, sharpened its benchmarking and
      launched an all-out assault on variation and inefficiency within its nine
      hospital system.

PMID- 19764365
TI  - Physician snapshot.
AB  - Predicting whether the nation faces a serious shortage of doctors is difficult,
      relying in part on assumptions about demand, demographics and distribution. This
      foldout offers a statistical snapshot of current and future physician
      demographics.

PMID- 19764366
TI  - Hospitals cut the cords.
AB  - When it comes to wireless technology in health care, mobility for caregivers is
      the name of the game. The 2009 Most Wired Survey reveals that tech-savvy
      hospitals are investing heavily in wireless capabilities, starting with
      infrastructure.

PMID- 19764367
TI  - AHA NOVA Awards.
AB  - Giving infants a healthy start or adolescents hope. Instilling healthy habits in
      one community or protecting another from a dangerous virus. The winners of this
      year's AHA NOVA Award set lofty goals and worked diligently to achieve them.

PMID- 19764368
TI  - Quality denominators.

PMID- 19764369
TI  - [A gigantic task ahead].

PMID- 19764370
TI  - [Secure the competence in social medicine!].

PMID- 19764371
TI  - [Mediterranean diet protects the heart. A new systemic review supports the diet
      recommendations].

PMID- 19764372
TI  - [Antibodies against cyclic citrullinated peptide indicate rheumatoid arthritis].

PMID- 19764373
TI  - [Treatment with insulin pump during hospital care should be questioned. Three
      cases illustrate the risk of ketoacidosis].

PMID- 19764374
TI  - [Attack-precipitating factors in migraine. Patient diary for better migraine
      attack control].

PMID- 19764375
TI  - [Self-belief--basis for successful rehabilitation. Confidence in one's own
      ability a strong predictor in orthopedic injury].

PMID- 19764376
TI  - [Good long-term effects of rehabilitation in warm climate].

PMID- 19764377
TI  - [How does ibuprofen affect alcohol degradation?].

PMID- 19764378
TI  - [Also extremely premature infants have a right to full-scale care].

PMID- 19764379
TI  - [The decision can't be made by the parents alone].

PMID- 19764380
TI  - [The question worth a more nuanced discussion].

PMID- 19764381
TI  - [SBU should investigate what is an evidence-based and cost-effective use of
      statins].

PMID- 19764382
TI  - [Physicians and the climate meeting in Copenhagen].

PMID- 19764383
TI  - [The Medical Products Agency: the tampon Ellen should be regulated as a
      pharmaceutical product].

PMID- 19764384
TI  - [The patient and the relatives could hear the heart beat--a rare case report in
      primary health care].

PMID- 19764385
TI  - [Hereditary breast and ovarian cancer syndrome].

PMID- 19764386
TI  - [Hereditary nonpolyposis colorectal cancer].

PMID- 19764387
TI  - [Familial adenomatous polyposis].

PMID- 19764388
TI  - [Li-Fraumeni syndrome].

PMID- 19764389
TI  - [Von Hippel-Lindau disease].

PMID- 19764390
TI  - [Multiple endocrine neoplasia type 1 syndrome].

PMID- 19764391
TI  - [Multiple endocrine neoplasia type 2 syndrome].

PMID- 19764392
TI  - [Familial atypical multiple mole melanoma syndrome--FAMMM].

PMID- 19764393
TI  - [Gorlin syndrome].

PMID- 19764394
TI  - [Peutz-Jeghers syndrome].

PMID- 19764395
TI  - [Neurofibromatosis von Recklinghausen].

PMID- 19764396
TI  - [The survey of syndromes with the risk of cancer in children age].

PMID- 19764397
TI  - [Tuberous sclerosis].

PMID- 19764398
TI  - [Hereditary pancreatitis].

PMID- 19764399
TI  - [Cowden syndrome].

PMID- 19764400
TI  - [Recommendation for prophylactic surgery for decreasing the risk of
      gynaecological cancer in women with hereditary risk].

PMID- 19764401
TI  - [Current methods in diagnostics and monitoring of patients with hereditary
      polyposis syndromes. Investigation of the small intestine].
AB  - BACKGROUNDS: Familial polypous syndromes include, in particular, familial
      adenomatous polyposis, Peutz-Jeghers syndrome and familial juvenile polyposis.
      The cumulative risk of developing cancer of the small intestine is higher and
      ranges between 5 to 13%. Close follow-up is therefore very important in the
      prevention of both malignant and benign complications of the basic disease.
      Currently there are many methods that can be offered to follow up patients with
      hereditary polyposis syndromes.The anatomy of the gastrointestinal tract can be
      investigated by endoscopy or double-contrast radiological techniques. The part of
      the small intestine between the duodenum and terminal ileum is difficult to reach
      by standard endoscopy and can only be judged by radiological enteroclysis, which
      has the disadvantage of exposing the patient to X-rays, moreover, it is
      impossible to examine the pathological findings histologically. However, new and
      more accurate enteroscopical (single and double-balloon, including
      intraoperative) methods and capsule enteroscopy have recently started to be used
      in routine clinical practice: Capsule endoscopy is an endoscopical method that
      enables us to examine the whole small intestine.This technology consists of
      swallowing a capsule the size of a bean that is later moved by motility of the
      gastrointestinal tract distally. A doctor then evaluates the record.
      Intraoperative enteroscopy is ever more often substituted by balloon enteroscopy.
      However, it remains a possibility when traditional double-balloon enteroscopy
      does not solve the patient's problems definitely; this occurs mainly in patients
      with intestinal adhesions or multiple lesions of the small intestine,
      endoscopically insolvable. Balloon enteroscopy is a modern endoscopic method that
      is used to examine the whole small intestine that also enables therapeutic
      efforts to be carried out when routine endoscopy is not successful. In some
      indications it has substituted intraoperative enteroscopy. CONCLUSION: These
      three methods are complementary, are connected in the examination algorithm and
      cannot be replaced by each other. Some authors consider them the golden standard
      in investigating the small intestine.

PMID- 19764402
TI  - [Limitations of genetic testing in oncology].
AB  - Genetic testing of cancer syndromes is based on the existing knowledge of
      monogenic causes of oncologic diseases. In cases of high-risk genes, the findings
      concerning the carrier status of pathogenic mutation can be of clinical use in
      the prediction of risks and for preventive care. In non-carriers in families with
      mutation in the high-risk gene, the risk of cancer diseases may not be the same
      as the population risk and some preventive follow-up is recommended. The clinical
      use of genes with mild or moderate risk of cancer is problematic and could lead
      to distorted conclusions about the actual cause of the familial form of the
      disease. Predictive testing in genes with moderate risk of cancer (2-3 times) is
      not offered, or the non-carriers are followed in the same way as carriers. The
      use of genes with mild risk is not recommended in clinical practice. Molecular
      genetic testing also has its limitations and its quality depends on the methods
      and technology used and the existing knowledge of the significance of mutations.
      In some variants it is not clear yet whether they are just insignificant
      polymorphisms or pathogenic mutations. The interpretation of test results in the
      context of the whole family history is important.

PMID- 19764403
TI  - [Prerequisites for preimplantation genetic diagnosis (PGD in carriers of
      mutations responsible for hereditary cancers].
AB  - BACKGROUNDS: Carriers of hereditary mutations in cancer susceptibility genes
      represent a limited but high-risk population characterized by a high probability
      of cancer development, frequently with its manifestation in early age and with a
      50% chance of pathogenic allele inheritance by offspring. In case of monogenic
      disorders, preimplantation genetic diagnosis (PGD) could be used for
      characterization of the DNA region affected by pathogenic mutation in the early
      stages of an embryo created by in vitro fertilization (IVF). Therefore, the
      transfer of unaffected embryos could be performed based on the results of PGD
      genotyping, enabling the development of offspring not carrying the pathogenic
      alteration. AIM: Here we present the consensus of the collaborative group of the
      Society for Medical Genetics, the Czech Society for Oncology and other
      professionals for use of PGD in the Czech Republic for carriers of mutations in
      cancer susceptibility genes. We address the conditions, prerequisites, and limits
      of practical application of this method. We also point out specific issues of
      ovarian hyperstimulation in carriers of mutations in BRCA1, BRCA2, and p53,
      anticipating the increased risk of hormonally dependent breast and ovarian
      cancers development. CONCLUSIONS: We assume that a narrow but non-negligible
      subgroup of cancer susceptibility gene mutation carriers may benefit from
      PGD.They are mainly individuals deciding to undergo IVF and PGD recruited from
      mutation carriers with extreme concerns about transmitting the mutation to their
      children. The PGD in these individuals should be managed by a closely cooperating
      multidisciplinary team of professionals responsible for indication of PGD, giving
      complete information regarding the IVF and PGD procedures including their limits,
      evaluating individual risks and performing instrumental and laboratory procedures
      with respect to up-to-date good laboratory and clinical practice.

PMID- 19764404
TI  - [Commentary: preimplantation genetic diagnosis].

PMID- 19764405
TI  - [Commentary: the possibilities of (assisted reproduction techniques) in control
      of risk genes transfer to the offspring].

PMID- 19764406
TI  - [Commentary: preimplantation genetic diagnosis].

PMID- 19764407
TI  - [Evaluation of infection control activities in health care facilities in Akita
      Prefecture].
AB  - OBJECTIVE: Infection control is essential for health care facilities. Aiming at
      improving the activity for infection control, increasing number of health care
      facilities has settled infection control team (ICT) in this decade. However, the
      quality of infection control activity has not been evaluated. METHOD: The quality
      of infection control was investigated in 49 hospitals and 55 welfare institutions
      for the aged in Akita prefecture using a questionnaire. RESULT: All the hospitals
      with more than 400 beds or more had ICT; however, less than 50% of the hospitals
      with 399 beds or less had ICT. The coverage of full-time specialist for infection
      control remained at a low level. Collection and analysis of information such as
      the prevalence of multi-drug resistant microorganisms and the consumption of
      antibiotics remained at a low level. More than 88% of the facilities hoped for a
      regional infection control network system to improve infection control
      activities. Reciprocal help in case of outbreak, education, lectures, sharing
      rules on infection control, making guidelines and teaching materials for
      infection control, analysis of infection control-related epidemiological data and
      getting suggestions and recommendations from authorized infection control
      specialists were included in the strongly required functions of the network.

PMID- 19764408
TI  - [Proteasome degradation of protein C and plasmin inhibitor mutants: molecular
      mechanism of congenital protein deficiency].
AB  - In many inherited disorders, protein deficiency is one of the major aetiologies,
      but the molecular and cellular mechanisms remain unclear. We investigated the
      intracellular degradation of mutant proteins, using naturally occurring PC and PI
      mutants that lead to congenital deficiencies. We have shown that proteasomes are
      very important for the degradation of PC and PI mutants, irrespective of the
      presence or absence of N-glycosylation moieties. Furthermore, mannose trimming
      after glucose removal is very important for initiation of the degradation.
      Inhibition of glucose trimming of the mutant proteins accelerated degradation by
      the proteasomes, and initiation of the degradation occurs after mannose trimming
      of the middle chain of N-linked glycosylation by mannosidase I. The binding of
      molecular chaperons influenced by the presence of N-glycosylation moieties may
      affect the efficient degradation of the mutant proteins. Cotransfection of
      endoplasmic reticulum (ER) degradation enhancing alpha-mannosidase like protein
      (EDEM) accelerated the degradation of N-glycosylated PC. The mutant PC or PI
      molecules were ubiquitin-independently degraded by proteasomes. Autophagy does
      not appear to contribute to the degradation of PC and PI mutants. These findings
      might help to elucidate the molecular mechanisms and potential treatments of
      congenital deficiencies of proteins in a system of coagulation and fibrinolysis.

PMID- 19764409
TI  - Case of ductal adenocarcinoma ex pleomorphic adenoma of the lacrimal gland.
AB  - Ductal adenocarcinoma of the lacrimal gland is extremely rare; to our knowledge,
      only seven de novo cases and one case of ductal adenocarcinoma ex pleomorphic
      adenoma have been reported in the literature. Here, we report a case of ductal
      adenocarcinoma ex pleomorphic adenoma of the lacrimal gland. A 70-year-old
      Japanese female received the resection of the recurrent lacrimal gland tumor
      (second surgery), under the clinical diagnosis of recurrent pleomorphic adenoma,
      fifteen years after the initial surgical resection. The resected tumor was
      composed of recurrent pleomorphic adenoma and adenocarcinoma. Adenocarcinoma
      component showed infiltrative papillo-tubular or microcystic growth of carcinoma
      cells, which had pleomorphic large nuclei with prominent nucleoli and rich
      eosinophilic cytoplasm. Large dilated ducts with central comedonecrosis were
      observed. Accordingly, the diagnosis of ductal adenocarcinoma ex pleomorphic
      adenoma was made. The tumor recurred locally eight months after the second
      surgery, and tumor exenteration was performed(third surgery). The
      histopathological features of the third surgical specimen were as same as those
      of the second surgical specimen. In the previously reported eight cases and the
      present case of lacrimal ductal adenocarcinomas, recurrence took place in 5 cases
      and two patients died from multiple metastases. These data suggests that lacrimal
      ductal adenocarcinoma appears to have a poor prognosis, similar to salivary duct
      carcinoma, which is one of the most aggressive salivary carcinoma. And further
      study is needed to clarify the clinicopathological features of the lacrimal
      ductal adenocarcinoma.

PMID- 19764410
TI  - [Effect of ISO15189 accreditation in Clinical Laboratory Center of Toyama
      University Hospital].
AB  - Quality, cost, risk, and knowledge control are essential in clinical laboratory
      management. In addition, a benchmark set by a third party is important. However,
      it is very difficult to develop these systems without a guideline and an
      authoritative body to set the benchmark. ISO15189 issued in 2003 is an
      international standard of "medical laboratories--particular requirements for
      quality and competence". This international standard is superior as a guideline.
      ISO15189 specifies quality and competence particular to medical laboratories.
      Also, it can be used by medical laboratories to develop their quality management
      systems and assess their own competence, and by accreditation bodies to confirm
      or recognize the competence of medical laboratories. In Japan, the Japan
      Accreditation Board for Conformity Assessment (JAB) is an accreditation body of
      ISO15189. We were awarded ISO15189 accreditation on July 31, 2008. In this
      report, we summarize the preparations for ISO15189 accreditation and the effects
      on our laboratory.

PMID- 19764411
TI  - [Fetal cell carcinogenesis hypothesis and the prospect of future laboratory
      tests].
AB  - A novel hypothesis of carcinogenesis, the "fetal cell carcinogenesis" hypothesis,
      was established based on molecular evidence of thyroid carcinoma. In this
      hypothesis, cancer cells are derived directly from the remnants of fetal cells,
      instead of well-differentiated somatic cells by de-differentiation. For example,
      thyroid cancer cells are generated from three types of fetal thyroid cell,
      namely, thyroid stem cells (TSCs), thyroblasts, and prothyrocytes by
      proliferation without differentiation, which results in producing anaplastic,
      papillary, and follicular carcinoma, respectively. Genomic alternations, such as
      RET/PTC and PAX8-PPARgamma1 rearrangements and a mutation in the BRAF gene, play
      an oncogenic role by preventing thyroid fetal cells from differentiating. Fetal
      cell carcinogenesis effectively explains recent molecular evidence regarding
      cancer, including cancer stem cells, and it underscores the importance of
      identifying a stem cells and clarifying the molecular mechanism of organ
      development in cancer research. Further, it introduces two important concepts,
      the reverse approach and stem cell crisis. Analysis of the molecular behavior of
      a single cell will be a key technique in establishing future laboratory tests. On
      the other hand, mass analyses such as gene expression profiling, whole genomic
      scan, and proteomics analysis have definite limitations since they can only
      provide information based on many cells. In light of these aspects, we started a
      project to establish FACS-mQ (mRNA quantification after Fluorescence Activated
      Cell Sorting). In FACS-mQ, cells are sorted by a specific gene expression
      pattern, and the gene expression profile in sorted cells can be easily analyzed.

PMID- 19764412
TI  - [Epigenetics-related diseases and analytic methods].
AB  - Epigenetics is defined as the study of changes in gene function that are
      mitotically and/or meiotically heritable and that dp not entail a change in DNA
      sequence. Epigenetic regulation of gene expression plays a critical role in
      development and differentiation, X inactivation, genomic imprinting and several
      human diseases, including cancer. DNA methylation and histone modifications play
      an essential role in epigenetic gene expression. In this article, an outline of
      epigenetics and representative analytic methods are explained. Then, epigenetic
      alterations and clinical implications of diseases, such as cancer, genomic
      imprinting-related diseases, and others, are described. The great advance in
      epigenetic research, from basic to clinical, will bring significant benefits to
      human health and a broad range of life sciences.

PMID- 19764413
TI  - [Recognition mechanism of pathogen-associated molecular patterns and role of
      innate immune lymphocytes in fungal infection].
AB  - Cryptoccus neoformans, a yeast-like opportunistic fungal pathogen, causes fatal
      meningoencephalitis in patients with a compromised immune response, such as AIDS.
      Host defense against this pathogen is mediated by cellular immunity, and Th1
      related cytokines play central roles, whereas Th2 cytokines negatively regulate
      these responses. When C. neoformans invades host tissues, macrophages and
      dendritic cells recognize its components, which leads to the activation of innate
      immune lymphocytes. During this process, the contribution of TLR-2 and TLR-4 is
      controversial, and in contrast, the interaction of TLR9 with DNA from C.
      neoformans seems to be deeply involved through a MyD88-dependent signaling
      pathway. Recently, dectin-1, a C-type lectin receptor, has garnered attention as
      a sole receptor of beta-1,3-glucan, a major polysaccharide component of the
      fungal cell wall. However, mice with genetic disruption of this molecule do not
      show any impairment of the cytokine response and host defense against
      cryptococcal infection, suggesting that the contribution of dectin-1 is less
      likely. Following the recognition step, innate immune lymphocytes such as NKT
      cells and gammadelta T cells are accumulated and activated at the site of
      infection. Interestingly, NKT cells promote, whereas gammadeltaT cells suppress,
      Th1-based immune responses and host defense against this infection, as shown by
      attenuation and promotion of these responses in mice genetically lacking NKT
      cells and gammadeltaT cells, respectively. Thus, host defense immune responses to
      C. neoformans infection are critically regulated by recognition of its components
      through pattern recognition receptors, such as TLR9, and also by competing
      activities of NKT cells and gammadeltaT cells.

PMID- 19764414
TI  - [Advanced clinical laboratory studies in the graduate school of medicine--studies
      on pathogenic mechanisms of anti-phospholipid syndrome].
AB  - Anti-phospholipid syndrome (APS) is defined based on both clinical findings
      (recurrent arterial and/or venous thrombosis and recurrent fetal loss) and
      laboratory evidence of persistent anti-phospholipid antibodies (anti-cardiolipin
      antibodies, anti-beta2 glycoprotein I antibodies, or LA activity). However, the
      precise mechanism responsible for arterial and/or venous thromboembolic
      complications in APS patients remains unclear. To clarify the association between
      the various types of anti phospholipid antibodies (aPLs) and thrombotic
      complications, we examined the prevalence of seven types of aPLs [anti
      cardiolipin/beta2-glycoprotein I antibodies(anti-CL/beta2-GPI), anti
      phosphatidylserine/prothrombin antibodies(anti-PS/PT), anti-beta2-glycoprotein I
      antibodies (anti-beta2-GPI), anti prothrombin antibodies (anti-PT), anti-protein
      C antibodies (anti-PC), anti-protein S antibodies(anti-PS), and annexin V
      antibodies(anti-AN)] in 168 patients with systemic lupus erythematosus (SLE). We
      confirmed that the presence of anti-CL/beta2-GPI, anti-PS/PT, and anti-beta2-GPI
      is closely related to arterial thrombosis, and that the presence of anti-protein
      S is closely related to venous thromboembolism. Furthermore, our in-vitro
      experiment suggests that anti-CL/beta2-GPI and anti-PS/PT may cooperate to
      promote platelet activation, and may be involved in the pathogenesis of arterial
      thrombosis. On the other hand, anti-protein S led to APC resistance, which may
      represent an important mechanism responsible for the development of venous
      thrombosis. Furthermore, our study showed that anti-CL/beta2-GPI causes a
      persistently high-level expression of tissue factor on monocytes, and this may
      increase the risk of atherosclerosis.

PMID- 19764415
TI  - [Proposal for graduate school education in the future: from the viewpoint of the
      Department of clinical Laboratory in a university hospital].
AB  - Fujita Health University Hospital, located in Toyoake, is a large teaching
      hospital with 1,505 beds. The Department of Clinical Laboratory in our hospital,
      in which 136 medical technologists work, is one of the largest clinical
      laboratories in Japan. Medical technologists in our hospital are required not
      only to perform accurate laboratory examinations, but also to contribute to the
      medical care team. In addition, they must educate students and trainee medical
      technologists. Furthermore, they conduct research to develop and evaluate new
      laboratory methods. Thus, we hope that education in graduate schools of medical
      technology (Master's course), along with promoting the specialty of laboratory
      techniques, will develop students' clinical skills to examine patients and
      research skills to conduct studies.

PMID- 19764416
TI  - [Nutrition education from the perspective of human health].
AB  - Nutrition education is a very important tool for the promotion of human health.
      Epidemiological studies showed a strong association between postprandial glycemia
      and the cardiovascular risk. White rice is the staple food in Japan, but it is a
      high glycemic index diet. In our study, postprandial glucose levels were
      suppressed when viscous meals and barley were used as the side dishes and staple
      food with average-sized portions, respectively. Thus, information on the
      association between the traditional Japanese diet and health is still quite
      limited at this point. In conclusion, further human studies on food function are
      required in order to provide the public with accurate information.

PMID- 19764417
TI  - [Shokuiku promotion in the context of laboratory medicine --special health
      checkups and healthcare guidance].
AB  - Special health checkups and healthcare guidance focusing on metabolic syndrome
      (visceral fat syndrome) were started in FY 2008, with the goal of reducing the
      rate of patients with and those at high risk of developing metabolic syndrome to
      25% by FY 2015. In order to fulfill this goal, it is necessary to establish
      scientific and objective evaluation systems for visceral fat accumulation and
      dietary intakes, which is certainly achievable by introducing the concept of
      laboratory medicine, the standardization of both methods and measured values.
      Accordingly, the principle of Shokuiku (food and nutrition education) should be
      promoted, motivating all generations of Japanese people to practice healthy
      dietary habits, by fostering the acquisition of knowledge related to Shoku
      (food/diet/eating) and the ability to choose Shoku through various experiences.

PMID- 19764418
TI  - [Hemodynamic analysis of intracranial aneurysms].

PMID- 19764419
TI  - [Operative simulation using 3D virtual images].

PMID- 19764420
TI  - [Clinical and operative findings in patients with trigeminal neuralgia caused by
      brain tumors].
AB  - Trigeminal neuralgia (TN) is occasionally caused by cerebellopontine angle (CPA)
      tumors. Among 243 patients presenting with TN who had been operated on in our
      institute, 25 (10.3%) were caused by CPA tumors, which consisted of 11
      epidermoid, 9 acoustic tumors, and 5 meningiomas. Cases with TN caused by tumors
      were clinically investigated in comparison with those of idiopathic TN. No
      significant differences were found concerning sex and the affected side between
      patient groups with tumors and without tumors. Patients with tumors were
      significantly younger than those without tumors (p = 0.04). In about 30% of
      patients of both groups, the trigeminal division of pain extended to two or more
      branches. In more than half of patients with epidermoid, the affected trigeminal
      distribution was two or more branches Operative findings demonstrated that the
      trigeminal nerve was compressed by surrounding vessels in 12 of 25 patients with
      tumors. The encasement of the trigeminal nerve by the tumor was most frequent
      affecting pattern in epidermoids, while acoustic tumors and meningiomas tended to
      compress and distort the nerve. TN disappeared in all patients with tumors at
      discharge. 5 patients with epidermoid experienced recurrence of TN during the
      follow-up period. In 4 of them, no tumor regrowth was detected at the time of TN
      recurrence. The mechanism of TN recurrence without tumor regrowth remains
      unclear, but may be explained by the arachnoid adhesion around the trigeminal
      nerve, as described in the previous report.

PMID- 19764421
TI  - [Assessing the treatment for sacroiliac joint dysfunction, piriformis syndrome
      and tarsal tunnel syndrome associated with lumbar degenerative disease].
AB  - OBJECTIVE: Sacroiliac joint (SIJ) dysfunction, piriformis syndrome (PFS) and
      tarsal tunnel syndrome (TTS) produce symptoms similar to lumbar degenerative
      disease (LDD). Patients who have these diseases plus LDD sometimes experience
      residual symptoms after surgery for LDD. We therefore assessed the results of
      treatment of SIJ dysfunction, PFS and TTS associated with LDD. PATIENTS AND
      METHODS: We assessed 25 patients who underwent surgery for LDD and were affected
      with SIJ dysfunction (12 patients), PFS (7 patients) or TTS (6 patients). SIJ
      dysfunction was treated with rest, drugs, pelvic band and sacroiliac joint block.
      PFS was treated with rest, drugs, physical exercise, injection of local
      anesthetic into the piriformis muscle, and surgical resection of the piriformis
      muscle. TTS was treated with drugs and tarsal tunnel opening. We analyzed the
      improvement score and recovery rate (JOA score) for both LDD surgery and the
      treatment of SIJ dysfunction, PFS and TTS. RESULTS: Symptom improvement was
      observed in all patients with SIJ dysfunction and PFS and in 4 patients with TTS.
      The improvement score and recovery rate of treatments for SIJ dysfunction, PFS
      and TTS were lower than those of surgery for LDD. CONCLUSION: The improvement
      score and recovery rate of treatment for SIJ dysfunction, PFS and TTS were not as
      high as those for LDD. To enhance patient satisfaction, it is important to
      consider these complicating diseases when designing treatments for LDD.

PMID- 19764422
TI  - [Dilation of subarachnoid space around the optic nerve in a patient with subdural
      effusion: a case report].
AB  - A fifty-year-old man who had a history of minor head injury a month previously
      presented with headache, visual disturbance and papilloedema. Brain MR imaging
      showed bilateral subdural effusion and fat saturated orbital MR imaging
      demonstrated dilated subarachnoid space around the optic nerve. The diameter of
      the subarachnoid space behind the globe was 7.0 mm and that of the optic nerve
      was 3.5 mm. Bilateral simple drainage was performed to prevent deterioration of
      the visual disturbance. Light bloody fluid with a subdural pressure of 10.5 cmH2O
      was drained from the burr hole at the left side, and colorless fluid was drained
      from the right. Orbital MR imaging during continuous drainage revealed shrinkage
      of the subarachnoid space around the optic nerve. However, follow-up MR imaging 5
      months after drainage showed disappearance of the subdural effusion and the
      reappearance of the subarachnoid space around the optic nerve, even though the
      size was smaller than before surgery. These findings suggest that the diameter of
      the optic subarachnoid space co-relates with the intracranial pressure, and may
      be an indication for increased intracranial pressure.

PMID- 19764423
TI  - [Massive subarachnoid hemorrhage and intraventricular hemorrhage after
      transsphenoidal surgery of pituitary adenoma: a case report].
AB  - Intracranial hemorrhage (ICH) and subarachnoid hemorrhage (SAH) may develop due
      to pituitary apoplexy from pituitary adenoma. However, the occurrence of ICH or
      SAH after transsphenoidal surgery is very rare. Here, we report a case of delayed
      and massive subarachnoid hemorrhage and intraventricular hemorrhage after
      transsphenoidal surgery for a suprasellar pituitary adenoma.

PMID- 19764424
TI  - [C2 neurinoma with intracranial extension: a case report].
AB  - We report a rare case presenting with a C2 neurinoma, which extended beyond the
      foramen magnum, producing a huge mass at the clivus. A 10-year-old boy with
      medical history of glycogenosis type VIII and attention-deficit hyperactivity
      disorder had been suffering from progressing foramen magnum syndrome for 36
      months. MRI demonstrated a huge tumor, 70 mm in a diameter, which distributed in
      both the intra- and extra-spinal canal at the C2 level and extended into the
      intracranial space beyond the foramen magnum. The tumor was totally removed via
      the trascondylar fossa approach with C1 hemilaminectomy. Operative findings
      indicated that the tumor arising from extradural C2 nerve intruded into the
      intradural space, and extended beyond the foramen magnum. Foramen magnum tumors
      sometimes remain unrecognized until severe neurological deficits develop because
      of bizarre symptomatology. Surgical strategies with less invasiveness based on
      early diagnosis lead to successful recovery of neurological function.

PMID- 19764425
TI  - [A case of posttraumatic forehead cavernous angioma].
AB  - Cavernous angiomas of the bone are rare tumors. Skull cavernomas are even less
      frequent. Most cavernous angiomas of the bone are congenital tumors. In a review
      of the literature, we found only one case report of de novo generation of a skull
      cavernous angioma. We present a case of a 25-year-old woman who had experienced a
      head injury, and 7 years later exhibited a skull tumor at the exact region of the
      injury. We performed tumor resection and cranioplasty. Follow-up examinations
      revealed no recurrence or neurological defects. Pathological findings showed a
      cavernous angioma-like lesion with some atypical details. We finally diagnosed
      the lesion as a de novo cavernous angioma. Our case suggests that fine injury may
      result in de novo generation of bone cavernomas.

PMID- 19764426
TI  - [A de novo distal PICA aneurysm occurring 3 years after clipping of another
      distal PICA aneurysm: a case report].
AB  - Distal posterior inferior cerebellar artery (dPICA) aneurysms are rare with an
      incidence of approximately 1% of all intracranial aneurysms. The frequent reports
      of the non-branching aneurysms or tandem aneurysms in an identical artery may be
      related to the embryology of dPICA and the anterior inferior cerebellar artery
      which is distinct from other cerebral arteries, as characterized by a thin vessel
      wall and tortuous course. In this paper, the authors present a case of a 67-year
      old man with a ruptured de novo dPICA aneurysm in the tonsillomedullary segment,
      which occurred 3 years after clipping of a ruptured aneurysm in the identical
      segment of the dPICA. The patient had a history of smoking and uncontrolled
      hypertension. He presented with a sudden onset of severe headache and vomiting.
      On admission computed tomography demonstrated subarachnoid hemorrhage in the left
      cerebello-medullary cistern with intra-forth ventricular clots. Vertebral
      angiography demonstrated a saccular dPICA aneurysm just distal from the previous
      clip. Based on the angiographic characteristics of the aneurysm and the potential
      difficulty of a second clipping operation, coil embolization of the parent artery
      was performed. The postoperative course was uneventful except for the presence of
      hoarseness. The unusual development and location of ruptured de novo dPICA
      aneurysm may be explainable by uncontrollable risk factors, as well as by the
      embryological features of dPICA. Careful follow-up neuroimaging studies and
      management of risk factors should be continued even after complete neck clipping
      or coil embolization in cases of dPICA aneurysm.

PMID- 19764427
TI  - [Spinal subdural abscess in the cervical region: a case report].
AB  - The authors present a patient with a spinal subdural abscess (SSA) in the
      cervical region and review the relevant literature. A 48-year-old man suffering
      from intractable high fever and back pain was admitted to our hospital with a
      diagnosis of meningitis. Despite antibiotic therapy, his condition deteriorated
      and he developed neurological deficits including left hemiparesis, sensory
      disturbance and bladder dysfunction. MR images of the cervical spine with
      gadolinium contrast revealed a circumferentially enhancing lesion anterior to the
      spinal cord that extended from the C4 to C6 level and compressed the spinal cord.
      After an urgent laminectomy extending from C4 to C6, the subdural abscess that
      consisted of purulent material and a thick capsule was irrigated and drained.
      Staphylococcus aureus was cultured from the abscess and he received antibiotic
      therapy postoperatively for 14 weeks. The high fever and the back pain subsided
      immediately and his neurologic condition gradually recovered. The majority of SSA
      cases involve the thoracic or lumbar region and are rarely found in the cervical
      region. Because they are associated with a high morbidity, early diagnosis with
      MRI and urgent surgical interventions including decompressive laminectomy,
      copious irrigation and drainage followed by appropriate antibiotic therapy are
      vital.

PMID- 19764428
TI  - [Clinical standard of neurosurgical disorder (10). Syncope].

PMID- 19764429
TI  - [Pharmacodynamics of pain perception and polymorphism].
AB  - The regulation of biotransformation started with the mechanism of mass action
      between the concentrations of the substrates (product) and enzyme. Thereafter by
      understanding the protein tertiary structure, allosteric control mechanism
      appeared. The enzyme induction was brought into a new aspect by the development
      of genetic analysis. As a cellular economy, energy charge was found to be a new
      regulatory mechanism for glycolytic pathway. These regulatory systems showed a
      single concentration-effect curve of pharmacodynamics. By introduction of silent
      or non sense gene as in atypical cholinesterase, a given function was not
      operated. As most doctors are aware of the diverse sensitivity to opioids among
      patients, numbers and species of opioid receptors might be the cause. By
      extensive gene analysis, polymorphism may explain this phenotype. The
      polymorphism may also play an important role in the pain mechanism such as
      incidence of neuropathic pain and in the modulation of pain. You will find
      several curves of pharmocodynamics.

PMID- 19764430
TI  - [How can we cope with wide individual variations in pain intensity and opioid
      requirements after surgery?].
AB  - Intensity of postoperative pain and postoperative analgesic requirements are
      widely varied among patients. The most determinant significant aspect of
      postoperative pain is the site and type of surgery. For example, open abdominal
      surgery usually causes intense postoperative pain. Even in patients after the
      same type of surgery, however, there are wide individual variations in pain
      intensity and analgesic requirements. A variety of environmental factors can lead
      to such differences. In addition, genetic factors also can contribute to such
      differences. For example, a single nucleotide polymorphism A118G of human micro
      opioid receptor gene (OPRM1) may decrease analgesic efficacy of opioids and
      increase postoperative opioid requirements. Full elucidation of genetic factors
      that can affect pain sensitivity and/or opioid sensitivity may open new avenues
      for personalized pain treatment.

PMID- 19764431
TI  - [Genetic polymorphisms and human sensitivity to pain and opioids].
AB  - It has been known widely that sensitivity to pain and opioid analgesics varies
      widely among individual subjects. Because of this variability, a dose of an
      opioid analgesic that can produce satisfactory pain relief without adverse
      effects in some patients might cause underdosing or overdosing in other patients,
      which is often problematic in the clinic. Individual differences can be
      attributed to both genetic and environmental factors, although the relative
      influence of each of these factors can be diverse. Numerous molecules have been
      identifled to be involved in the transduction, conduction, transmission and
      modulation of pain, as well as pharmacological effects of opioids. Further, many
      technologies of genotyping polymorphisms, most often single nucleotide
      polymorphisms (SNPs), have been developed and advanced, leading to accelerated
      understanding of many associations between various genetic polymorphisms and
      sensitivity to pain and opioids. In this article, we review the evidence of these
      associations accumulated thus far.

PMID- 19764432
TI  - [Postoperative pain management following orthognathic surgery in consideration of
      individual differences--is the antinociceptive effect of fentanyl related to the
      genotype involving nucleotide at OPRM1?].
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 micro-opioid receptors,
      may be associated with the clinical effects of opioid analgesics. The study
      demonstrated whether any of five 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 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.

PMID- 19764433
TI  - [Side effects of opioid and gene variants].
AB  - There are individual differences in the analgesic effect and the side effect of
      the opioid to which genetic variation may be related. Analysis of micro-opioid
      receptor knockout mice indicated that inhibition of gastrointestinal transit by
      morphine is mediated by micro-opioid receptor. Our study suggested that
      gastrointestinal symptom (especially loss of appetite) as a side effect of opioid
      could be associated with the gene polymorphism of dopamine D2 receptor.
      Understanding of the relationships between gene polymorphisms and opioid
      sensitivities may lead to more-accurate prediction of the opioid sensitivity and
      opioid requirements in individual patients.

PMID- 19764434
TI  - [Implication of genetic polymorphism on neuropathic pain].
AB  - Various conditions are categorized to neuropathic pain, many of which are
      intractable requiring investigation using multiple approaches. Genetic
      polymorphism is one of such research fields that have provided much insight into
      conditions including postherpetic neuralgia, CRPS and postoperative pains. The
      research in genetic polymorphism is also expected to help expedite realization of
      the genomic personalized medicine in that selection and dosage of medication are
      determined according to each patient's specific set of requirements. In addition,
      the genetic polymorphism research effort in the field of drug discovery in areas
      such as metabolism, transporters and receptors is also expected to contribute to
      the clinical practice by expanding our knowledge in each of those areas.

PMID- 19764435
TI  - [Gene polymorphisms in ATP (purinergic) receptors and pain sensitivity].
AB  - Extracellular adenosine 5'triphosphate (ATP) has been recognized as a
      neurotransmitter and/or neuromodulater in the nervous systems, through acting on
      specific receptors, P2 purinergic receptors on the cell surface. P2 purinergic
      receptors are divided into two classes; P2X receptors, which are ATP-gated cation
      channels and subdivided into seven subtypes, and P2Y receptors, which are
      heptahelical G-protein coupled receptors and subdivided into eight subtypes.
      Recent studies revealed that ATP and its receptors are involved in peripheral and
      central nociceptive transmissions, including the mechanism of neuropathic pain.
      On the other hand, many gene polymorphisms, most of which are single nucleotide
      polymorphisms (SNPs), reportedly exist in the genes encoding P2X and P2Y
      receptors. Further, some of the SNPs have been revealed to cause changes of
      receptor functions. Our recent study showed one of these SNPs tends to be
      associated with the pain sensitivity induced by the cold stimuli. Association
      studies of these polymorphisms in the gene encoding P2X and P2Y receptors with
      the pain sensitivity and effects of analgesics may provide novel and useful
      suggestions for personalized pain managements.

PMID- 19764436
TI  - [Serotonin receptor gene polymorphism and analgesic sensitivity].
AB  - There are gene polymorphisms changing the expression or activation of the
      serotonin (5-HT) receptors, which are associated with pain. This review showed an
      availability of 5-HT2A receptor gene polymorphism in analgesic sensitivity. To
      search gene polymorphisms related to analgesic sensitivity is important to
      further effective pain management. In future 5-HT2A receptor gene polymorphisms,
      together with polymorphisms of other genes, may greatly contribute to effective
      postoperative pain management and personalized medicine.

PMID- 19764437
TI  - [Anti-opioid action of glutamate-NMDA receptor systems underlying morphine
      analgesic tolerance].
AB  - Although the opioid analgesics such as morphine represent an important class of
      agents for the treatment of severe clinical pain, the development of tolerance
      and dependence often overshadows the therapeutic advantages of morphine and
      related opioids in individuals undergoing long-term treatments. The mechanisms
      underlying opioid tolerance are not fully understood, but appear to be comprised
      of two types of plasticity or counter-adaptation, at the cellular level and
      through neuronal circuits. Current studies mostly emphasize the cellular
      adaptation mechanisms, which include altered gene expression and receptor
      desensitization due to phosphorylation and endocytosis. However, the mechanisms
      underlying opioid tolerance and dependence are not always explained by cellular
      adaptation mechanisms alone. This review focuses on the plasticity in neuronal
      circuits achieved through an enhancement of so-called anti-opioid glutamate/NMDA
      receptor synaptic activities. There have been also conceptual advances in
      understanding the changes to supporting systems, which include the altered
      expression of key molecules regulating the anti-opioid system through neuron
      glial networks. We also introduce a new approach using in vivo electroporation to
      identify the brain loci responsible for morphine tolerance and dependence.

PMID- 19764438
TI  - [Evaluation of target-controlled infusion for propofol in patients with chronic
      renal failure undergoing living-related renal transplantation].
AB  - BACKGROUND: As we have no information whether target-controlled infusion (TCI)
      for propofol, using pharmacokinetic parameters obtained without chronic renal
      failure, is available to estimate the drug concentration, we examined the blood
      concentration of propofol on the patients with chronic renal failure to evaluate
      the reliability of TCI of propofol. METHODS: Ten patients with chronic renal
      failure undergoing hemodialysis, from 20 to 60 years of age, were scheduled for
      living-related renal transplantation. Propofol was administrated with our TCI
      system at the target blood concentration of 4 microg x ml(-1) for three hours.
      Blood samples were obtained at 30, 60, 90, 120, and 180 minutes after starting
      propofol delivery, and at the emergence from anesthesia to measure propofol
      concentration. RESULTS: There was no tendency of increasing the drug
      concentration in proportion to the time of propofol infusion. As for the
      concentration at emergence, mean estimated concentration of propofol was 1.6 mg x
      ml(-1), showing a good correlation between measured and estimated concentrations.
      CONCLUSION: TCI system for propofol provided a good estimation of the blood
      concentration of propofol in patients with chronic renal failure undergoing
      living-related renal transplantation.

PMID- 19764439
TI  - [Comparison of intravenous fentanyl analgesia and epidural analgesia for
      postoperative pain relief].
AB  - BACKGROUND: Epidural analgesia is available for postoperative pain relief except
      for the patients with bleeding tendency or under anticoagulation. Intravenous
      fentanyl analgesia can be applied for such patients but its effect has not been
      evaluated enough. We compared these two methods after abdominal surgery. METHODS:
      In the intravenous fentanyl analgesia group (group iv, n = 15), 0.7 microg x kg(
      1) x hr(-1) fentanyl infusion was started during operation and decreased to 0.5
      microg x kg(-1) x hr(-1) on the next morning. In the epidural analgesia group
      (group e, n = 15), 0.4 microg x kg(-1) x hr(-1) fentanyl and 5 ml x hr(-1) 1%
      mepivacaine infusion was started during operation. The VAS pain score (at rest
      and at coughing), the level of consciousness, respiratory and cardiovascular
      depression, nausea and vomiting were evaluated for 3 days. RESULTS: The VAS
      scores at rest were similar in two groups but the VAS scores at coughing were
      similar or lower in the group iv. In the group iv, five patients suffered from
      nausea and one patient had somnolence. In the group e, only one patient had
      nausea but two patients had hypotension. CONCLUSIONS: Intravenous fentanyl
      analgesia is safe and possibly more effective than epidural analgesia.

PMID- 19764440
TI  - [Case of neurocardiogenic syncope with asystole during insertion of epidural
      catheter].
AB  - A 25-year-old healthy woman was scheduled for enucleatic myomectomy under
      combined epidural and general anesthesia. During insertion of a lumbar epidural
      catheter, sudden loss of consciousness associated with asystole developed. This
      condition was quickly restored by rapid fluid infusion, administration of
      atropine sulfate (0.5 mg) and oxygen (6l x min(-1)). Diagnosis of
      neurocardiogenic syncope (NCS) was made by previous episodes of fainting revealed
      at that point. An epidural catheter was placed under sedation with midazolam 2
      mg. Surgery was performed uneventfully under sevoflurane anesthesia. Since NCS
      occurs recurrently in a susceptible individual, it is important to identify
      previous syncopal episode preoperatively. If such an event is anticipated,
      prevention including proper communication to reduce patient's anxiety, careful
      vigilance on both patient and monitor during procedure, gentle maneuver to reduce
      pain and use sedative and/or anticholinergic agents must be considered.

PMID- 19764441
TI  - [Spinal cord stimulation (SCS) as a treatment for the spread phenomenon related
      to complex regional pain syndrome type- I (CRPS-I )].
AB  - The authors describe an experience of spinal cord stimulation (SCS) in a 30-year
      old woman who developed complex regional pain syndrome type-I (CRPS-I) with
      spread phenomenon. She had received lumbar SCS under a diagnosis of CRPS-I in her
      left leg for 8 years. She had refractory pain in her right arm for the recent two
      years. There was no new lesion explaining her refractory pain on physical or
      radiological examination. Thus, the pain in her right upper arm was considered as
      spread phenomenon of CRPS-I. Test stimulation with cervical epidural spinal
      electrode showed good results and the pulse generator was implanted. It is
      suggested that the symptom of CRPS-I involving spread phenomenon was possibly due
      to a cortical reorganization. But a certain effect of SCS may be contributing to
      the favorable results of test stimulation for the treatment of CRPS-I with spread
      phenomenon in this case.

PMID- 19764442
TI  - [Intraoperative ventricular or supraventricular tachycardia? A case report].
AB  - A 68-year-old man with a history of paroxysmal supraventricular tachycardia
      developed wide QRS complex tachycardia one minute after induction of general
      anesthesia. As the wide QRS complex tachycardia appeared to be ventricular and
      pulsation of the radial artery could not be felt, intravenous antiarrhythmic
      drugs were given. Surgery was postponed. Postoperative electrophysiological study
      revealed ectopic atrial tachycardia. Catheter abration was performed. Regular P
      waves were noticed by precise review of the intraoperative electrocardiogram. The
      intraoperative tachycardia was thought to be supraventricular in origin.

PMID- 19764443
TI  - [Tracheal compression caused by hematoma and felt strips around an anastomosis
      site following repair of thoracic aneurysm: a case report].
AB  - Respiratory complication is common after a repair of thoracic aneurysm, although
      tracheal compression caused by hematoma and felt strips following surgery is a
      rare cause. We report the case of a patient who experienced difficult weaning
      from ventilator after a repair of a thoracic aortic aneurysm and was diagnosed as
      a tracheal compression outside of trachea revealed by bronchoscopy and chest CT
      scan. Re-operation was successfully performed to relieve the compression under
      monitoring by bronchoscopy. Patient was disconnected from the ventilator three
      weeks after the reoperation and transferred to a rehabilitation hospital.

PMID- 19764444
TI  - [Anesthetic management for a patient with heparin-induced thrombocytopenia (HIT)
      undergoing off-pump coronary bypass surgery using argatroban, a direct thrombin
      inhibitor].
AB  - HIT type II is one of the severe complications of heparin therapy. The antibody
      for the heparin-PF 4 complex, which causes thrombocytopenia of less than 100 x
      10(3) microl(-1), thrombosis and DIC-like symptoms, is produced. We managed the
      patient with HIT type II undergoing off-pump CABG. Anesthesia was induced and
      maintained with fentanyl, midazolam, vecuronium and sevoflurane. The operation
      was performed using argatroban, a direct thrombin inhibitor, as an anticoagulant.
      Intraoperative activated coagulation time (ACT) was maintained above 250 sec with
      2.5-5.0 microg x kg(-1) x min(-1) of argatroban infusion without bolus injection
      and all the procedures were successful.

PMID- 19764445
TI  - [Pulmonary edema due to laryngospasm immediately after extubation].
AB  - We describe a case of negative pressure pulmonary edema (NPPE) followed by
      laryngospasm occurred immediately after extubation. A 56-year-old man with a
      tumor at the site of ureteroneocystostomy underwent left ureterectomy and partial
      resection of the neobladder under general anesthesia. The tracheal intubation was
      difficult with glade 3 of Cormack classification. Anesthesia was maintained with
      sevoflurane, nitrous oxide, and oxygen. After fully awake extubation, the upper
      airway obstruction due to laryngospasm was observed. A nasal airway was inserted,
      but face mask ventilation was impossible. Ventilation became possible with SpO2
      of around 40%, and spontaneous respiration appeared. The patient was nasally
      intubated with a fiberoptic bronchoscope. Furosemide was administered in ICU and
      mechanical ventilation with 5cmH2O PEEP was started. Seventeen hours later, the
      pulmonary edema disappeared and he was successfully extubated without any
      complications. It was warned that laryngospasm would occur even after the full
      emergence, leading to NPPE.

PMID- 19764446
TI  - [Cancer and esophagobronchial fistula: a case report].
AB  - Palliative esophageal bypass surgery for patients with esophageal cancer and
      esophagobronchial fistula aims restoring the ability of swallowing as well as
      preventing pulmonary aspiration. Perioperatively, there are several problems in
      respiratory management for such patients. Repeated episodes of pulmonary
      aspiration exaggerate bronchopneumonia. Positive pressure ventilation may cause
      air leakage via fistula resulting in inadequate ventilation, distension of the
      stomach and regurgitation of gastric contents; thus, maintaining of spontaneous
      ventilation is a crucial concern. Here we report an anesthetic management of a 51
      year-old woman with esophageal cancer and esophagobronchial fistula undergoing
      esophageal bypass surgery. We could not apply neuraxial block due to
      hypocoagulability. We performed awake tracheal intubation, and general anesthesia
      was maintained using sevoflurane supplemented by morphine, fentanyl and ketamine
      under spontaneous ventilation until the resection of gastroesophageal junction
      and the installation of a drainage catheter into the esophagus. Muscle relaxation
      required for surgery was sufficiently obtained by sevoflurane anesthesia without
      administration of muscle relaxants. After the installation of the drainage
      catheter, the lungs were ventilated mechanically until the end of surgery. The
      surgery was uneventful. The patient emerged from general anesthesia smoothly, and
      was extubated. The postoperative course of this patient was also uneventful.

PMID- 19764447
TI  - [Obstetric anesthesia training in the USA, experience of the Cleveland Clinic;
      Cleveland, Ohio].
AB  - In Japan, the re-organization of obstetrical medical system is needed and this
      project is ongoing under Japanese government initiative. However the ratio of
      using neuraxial analgesia (NA) during labor in Japan has been low and, increased
      demand for NA during labor is anticipated in near future. To prepare for these
      demands, the adequate number of obstetrical (OB) anesthesia specialists in the
      advanced OB hospital is necessary. However, there is no official training program
      for OB anesthesiologists in Japan. This article reports the clinical practice of
      the OB anesthesia in one of the biggest hospitals in the United State, the
      Cleveland Clinic, from the view of an OB anesthesia clinical fellow.

PMID- 19764448
TI  - [Child neurologists and supporting systems for children with developmental
      disorders].

PMID- 19764449
TI  - [An 8-year-old boy presenting with progressive extrapyramidal symptoms during
      total parenteral nutrition].

PMID- 19764450
TI  - [Cerebral palsy].
AB  - Great advances have been made in the causes, lesions and symptoms of cerebral
      palsy over the years. Children with athetosis have lesions of the ventral lateral
      nuclei of the thalamus and putamen. Cocontraction and overflow are considered
      essential problems in athetosis. Some patients with a lesion of the ventral
      lateral nucleus of the thalamus do not show any involuntary movements. Children
      with periventricular leukomalacia demonstrate various patterns of the hip, knee
      and ankle in response to bearing body weight. Some of these patients exhibit
      ataxia, tremor and mouth opening triggered by voluntary movements. They have
      various central visual disorders or visual cognitive disorders. They also exhibit
      paroxysmal ocular downward deviation. In early infancy with spastic diplegia,
      there is no isolated extension of the knee or leg elevation. Hemiplegia results
      from stroke of the middle cerebral artery or venous infarction during the fetal
      or neonatal period. Border-zone infarction results from partial asphyxia.

PMID- 19764451
TI  - [Study on the details of the children who require special support education in
      the regular classroom].
AB  - The purpose of this study is to clarify details of children who have special
      supportive educational needs in the regular classroom environment and to reveal
      the result of their health check-ups at 1.5 and 3 years of age. Between April
      2004 and March 2005, 503 students from regular classes visited with their parents
      to the education support center as a result of behavioral or learning problems.
      In addition to checking the developmental history of each case, behavior
      observation and intelligence test (WISC III ) were completed by clinical
      psychologists. Parents of 258 children who requested make interviews with medical
      specialists were subsequently interviewed independently for one hour. The parents
      were given advice depending on the results of both the examinations and reports
      by clinical psychologists. Interviews and reports including developmental
      history, behavior observation, intelligence test results and school records were
      summarized by the authors (medical specialists and a teacher from a handicapped
      school). Among these children, 171 were diagnosed with developmental disorders,
      103 had high function pervasive developmental disorders (HFPDD), 75 had mental
      retardation (MR) including borderline intelligence, and 26 had both autism and
      MR. Furthermore, 24 children were diagnosed as AD/HD and 23 as having a learning
      disorder (LD). Although some developmental problems had been identified in half
      of the children with autism at 1.5 or 3 years of age, they had not been followed
      up sufficiently. Further, few children with LD or AD/HD had been identified
      during health check-ups. These results suggest that we should reconsider the
      health check-ups system for the children with LD and AD/HD as well as autism and
      establish a follow up system for them.

PMID- 19764452
TI  - [Re-evaluation of ketogenic diet therapy for childhood refractory epilepsy].
AB  - We conducted a retrospective survey of the efficacy of ketogenic diet therapy
      (KD) for childhood refractory epilepsy. The subjects were 54 patients (male: 19;
      female: 35) undergoing KD between 1984 and 2007 in our hospital. We defined
      marked improvement as being seizure-free and satisfactory improvement as a
      reduction of the seizure frequency by more than 50%. KD was started at ages
      ranging from 6 months to 15 years (median:4 years), and maintained for 1 month to
      as long as 7 years. Twenty-nine patients (54%) discontinued KD within 1 year of
      its initiation. As the results, 18.5 and 35% of the patients showed marked and
      satisfactory improvement, respectively, at 1 year after starting KD. A greater
      than satisfactory improvement was achieved in 80% of those showing transitional
      state from West to Lennox-Gastaut syndrome (n = 5), 100% of those with epilepsy
      with both focal and generalized seizures (n = 3), 46% of those with severe
      myoclonic epilepsy in infants (n = 13), 33% of those with cryptogenic myoclonic
      astatic epilepsy (n = 3), 25% of those with symptomatic localization-related
      epilepsy (n = 8), 20% of those with Lennox-Gastaut syndrome (n = 5), and 12% of
      those with symptomatic generalized epilepsy (n = 17). There were no serious side
      effects. Five patients discontinued KD despite their satisfactory improvement
      because they disliked the taste of the meals. KD therapy is worth considering for
      children with refractory epilepsy, but a more palatable KD menu needs to be
      developed for Japanese patients to maintain their long-term compliance with the
      therapy.

PMID- 19764453
TI  - [Simple and useful evaluation of motor difficulty in childhood (9-12 years old
      children ) by interview score on motor skills and soft neurological signs--aim
      for the diagnosis of developmental coordination disorder].
AB  - Many children with developmental disorders are known to have motor impairment
      such as clumsiness and poor physical ability;however, the objective evaluation of
      such difficulties is not easy in routine clinical practice. In this study, we
      aimed to establish a simple method for evaluating motor difficulty of childhood.
      This method employs a scored interview and examination for detecting soft
      neurological signs (SNSs). After a preliminary survey with 22 normal children, we
      set the items and the cutoffs for the interview and SNSs. The interview consisted
      of questions pertaining to 12 items related to a child's motor skills in his/her
      past and current life, such as skipping, jumping a rope, ball sports, origami,
      and using chopsticks. The SNS evaluation included 5 tests, namely, standing on
      one leg with eyes closed, diadochokinesia, associated movements during
      diadochokinesia, finger opposition test, and laterally fixed gaze. We applied
      this method to 43 children, including 25 cases of developmental disorders.
      Children showing significantly high scores in both the interview and SNS were
      assigned to the "with motor difficulty" group, while those with low scores in
      both the tests were assigned to the "without motor difficulty" group. The
      remaining children were assigned to the "with suspicious motor difficulty" group.
      More than 90% of the children in the "with motor difficulty" group had high
      impairment scores in Movement Assessment Battery for Children (M-ABC), a
      standardized motor test, whereas 82% of the children in the "without motor
      difficulty" group revealed no motor impairment. Thus, we conclude that our simple
      method and criteria would be useful for the evaluation of motor difficulty of
      childhood. Further, we have discussed the diagnostic process for developmental
      coordination disorder using our evaluation method.

PMID- 19764454
TI  - [Deficiency of REM sleep in a patient with pontine cavernous hemangioma].
AB  - A 15-year-old girl had no REM sleep presumably due to a pontine cavernous
      hemangioma was reported. Her brain MRI revealed a cavernous hemangioma extending
      from the dorsal pontine to the medulla. She manifested truncal ataxia, facial
      nerve palsy, and ocular motor apraxia. She could not sleep in the supine position
      due to the sleep apnea accompanied with loud snoring. Overnight polysomnography
      (PSG) was performed for detection of obstructive sleep apnea syndrome (OSAS). In
      addition to severe OSAS and Cheyne-Stokes-like respiration at wake after sleep
      onset, her 1st PSG study revealed no periods with rapid eye movement, EEG
      characteristic of REM sleep, atonia and variation on respiratory and heart rate.
      Even after effective therapy for OSAS with non-invasive positive airway pressure
      ventilation (NPPV), her 2nd PSG also failed to show stage REM. These findings
      suggest that this pontine cavernous hemangioma disturbed her REM-on system. This
      is the first report of an individual with long-term loss of REM sleep and a
      valuable case for the understanding of anatomical structures of the REM-on system
      and the role of REM in memory consolidation.

PMID- 19764455
TI  - [Long term clinical course of Canavan disease--a rare Japanese case].
AB  - Canavan disease (CD), which is a rare disease in Japan, is an autosomal-recessive
      neurodegenerative disorder caused by mutations in aspartoacylase, an enzyme that
      deacetylates N-acetylaspartate to generate free acetate in the brain. CD affected
      children usually die by the age of 10 years. Here we report a long term clinical
      course of a 21-year-old Japanese woman who was diagnosed as CD at the age 4. This
      patient is the only reported case of CD in Japan that has been biochemically
      confirmed. Although this patient is currently bed-ridden with spastic
      quadriplegia and severe mental retardation, her general condition is quite
      stable. This patient showed a milder clinical course compared to the majority of
      CD patients. Because this is the only reported case of CD in Japan, we
      hypothesize that there might be an ethnic phenotypic polymorphism in CD.

PMID- 19764457
TI  - [Case of confusional migraine associated with transient increased blood flow in
      cerebral hemisphere].

PMID- 19764456
TI  - [Effects of piracetam therapy in a case of Lance-Adams syndrome].
AB  - We report a 17-year-old female patient with Lance-Adams syndrome caused by anoxic
      encephalopathy during a severe attack of bronchial asthma. She had difficulty in
      writing because of action myoclonus in her arms. She also exhibited freezing gait
      and was unable to walk without cane. Although her gait disturbance resembled
      those seen in patients with parkinsonism secondary to anoxic encephalopathy,
      surface electromyography revealed that it was caused by action myoclonus in her
      legs. The presence of giant somatosensory evoked potentials and enhanced cortical
      reflexes in response to the electrical stimulation to her posterior tibial nerves
      supported our diagnosis. A combined therapy with valproate sodium, clonazepam and
      piracetam (15 g/day) was not effective. However, her freezing gait remarkably
      improved and she was able to walk without help, after the treatment with
      sufficient dose of piracetam (21 g/day). Cortical hyperexcitability as revealed
      by electrophysiological examination also improved. We concluded that the combined
      therapy with antiepileptic drugs and piracetam was effective in the treatment for
      action myoclonus. However, because the effects seemed dose-related, the dosage of
      piracetam needed to be increased until the optimum effects were obtained.

PMID- 19764458
TI  - [Correlation between renal tubular dysfunction and serum carnitine deficiency in
      cases with valproate therapy].

PMID- 19764459
TI  - [Case of Pitt-Hopkins syndrome].

PMID- 19764460
TI  - [Various aspects of acinar lesions--the key finding of pulmonary tuberculosis on
      HRCT].
AB  - Acinar lesions, a pathologist's naming for granulomatous lesions formed in the
      peripheral air space, that is, in the bronchiole or its adjacent alveolar space,
      is very characteristic and pathognomonic for tuberculosis on HRCT imaging. As a
      radiological term, it is equal to centrilobular nodule or branching shadow, or
      tree-in-bud appearance in the recent trend. It is universally seen in most of
      tuberculosis cases, irrespective of its stage or extensity. Although thus common,
      its appearance is not always uniform. Firstly they are not well defined in some
      cases. Exudative tendency in pathological process may explain for this
      appearance. Secondarily they are not always arranged in an orderly manner or in
      other words centrilobular manner on CT, but often in a random fashion.
      Pathologically this phenomenon can be explained by the randomness of formation
      site of granulomas or by scarring in spontaneous healing process of the disease.
      Finally, although rare, an extreme pattern, in which acinar lesions are diffusely
      disseminated in both lung fields without other type of lesions, is well known as
      Oka's Classification of Pulmonary Tuberculosis Type IIB. This rare type of
      tuberculosis could be formed through indolent dissemination of bacilli via the
      airway or from the hematogenous dissemination. It should also be noted that in
      tuberculous pneumonia, especially when it develops in emphysematous lung, acinar
      lesions is not seen, making differential diagnosis difficult.

PMID- 19764461
TI  - [The chest CT findings and pathologic findings of pulmonary tuberculosis].
AB  - The past research of the radiologic manifestations of pulmonary tuberculosis in
      Japan was based on morphological pathology of the untreated patient autopsy. I
      would like to show the chest CT scan of tuberculosis diseases with caseous
      granuloma at its exudative reaction, proliferative reaction, productive reaction,
      cirrhotic reaction until self cure. This progress reflects the normal cell
      mediated immunological responses. Also I would like to show the cavitation of
      granuloma, which results from liquefaction of caseous materials during the course
      and results in the formation of the source of infection. And finally I would like
      to show the morphological differences of acinous lesion, acino-nodular lesion and
      caseous lobular pneumonia. These differences reflect the amount of bacilli
      disseminated in the peripheral parts under the lobules. In this study, I do not
      show old age cases and HIV positive cases, who do not form typical granuloma due
      to the decreased cell mediated immnunity and whose X ray findings are atypical.

PMID- 19764462
TI  - [Chest X-ray image findings of Mycobacterium avium complex (MAC) lung disease].
AB  - Recently Mycobacterium avium complex (MAC) lung disease has increased in number
      remarkably in Japan. The MAC lung disease is divided into four types: a nodular
      bronchiectatic disease, a fibrocavitary disease, a hypersensitivity like disease,
      and a disseminated disease. Since the latter two types are rare, it is important
      in the diagnosis and treatment to understand the images of the former two.
      Formerly the fibrocavitary disease was more common, which occurred in the
      preceding tuberculous lesion frequently and showed images similar to
      tuberculosis. But recently the nodular bronchiectatic disease has increased in
      number particularly. Characteristic feature of this type is involving the right
      middle lobe and left lingual segment overwhelmingly in nonsmoking,
      immunocompetent, middle-aged women. Common CT manifestations of the nodular
      bronchiectatic disease include nodules just beneath the pleura, consolidation
      including bronchiectasis, and, lung volume shrinkage.

PMID- 19764463
TI  - [Radiographic findings of pulmonary nontuberculous mycobacteriosis other than
      Mycobacterium avium complex].
AB  - Almost all nontuberculous mycobacteria (NTM) cause opportunistic infection.
      Therefore, the radiographic findings of NTM have a tendency of nonspecific
      patterns modifying the predisposing conditions or diseases and we could not
      extract species specific radiographic characterizations in that situations. In
      this review, the NTM cases without predisposing conditions or diseases are
      submitted essentially. Mycobacterium kansasii cases show more or less the same
      patterns with TB cases. Mycobacterium fortuitum case shows nonspecific
      consolidations. Mycobacterium xenopi case shows solitary cavity in the upper lobe
      area. Mycobacterium gordonae case shows the same cavitary pattern. Mycobacterium
      abscessus case shows widely scattered tree-in-bud appearance foci. Weak virulence
      NTM like as Mycobacterium xenopi or Mycobacterium gordonae may form solitary
      cavity without predisposing conditions. The pattern of bronchial wall thickening
      seems to be one of the specific findings with NTM pulmonary infection.

PMID- 19764464
TI  - [Differential diagnosis of pulmonary mycobacterial infection; radiological
      findings mimicking tuberculous or nontuberculous mycobacterial pneumonia].
AB  - Radiological imaging is one of the important clues for diagnosis of pulmonary
      mycobacterial infection. Differential diagnosis of pulmonary tuberculosis and
      nontuberculous mycobacterial infection is following; bacterial pneumonia,
      bronchopneumonia, mycoplasma pneumonia, pulmonary fungal infection, diffuse
      panbronchiolitis, sinobronchial syndrome, sarcoidosis, Wegener's granulomatosis,
      bronchiolealveolar carcinoma, pulmonary malignant lymphoma, and pneumoconiosis.
      Characteristic findings of bronchial tuberculosis are chronic productive cough
      with no radiological finding, lobar atelectasis, or mucoid impaction of bronchi.
      Radiologic findings of pulmonary mycobacterial infection are multiple
      infiltration, centri-lobular nodules which sometime adhere, cavity, and solitary
      nodule, however, these findings mimic bacterial pneumonia and bronchopneumonia
      especially in case of immunosuppressive patients. Pulmonary tuberculosis
      predominantly appears in upper lobe and the top of lower lobe of S6. Nontuberous
      mycobacterium pulmonary infection predominantly affects middle lobe and lingual
      lobe, accompanying with bronchial wall thickness and bronchiectasis. It is
      difficult to diagnose pulmonary mycobacterial infection using pulmonary imaging
      alone, therefore bacterial examination from sputum or bronchoalveolar lavage
      fluid should be necessary.

PMID- 19764465
TI  - [A case of sternoclavicular joint tuberculosis with renal failure due to
      rifampicin].
AB  - A 79-year-old man was admitted to a previous hospital complaining of left
      precordial swelling. Chest CT scan showed destruction of left sternoclavicular
      joint and a mass of 5 cm in diameter. Needle biopsy was performed and the
      diagnosis of sternoclavicular joint tuberculosis was made on the basis of
      presence of M. tuberculosis in the specimen. The patient was treated with
      isoniazid, ethambutol, rifampicin, and pyrazinamid but he developed renal
      failure. Then, he was transferred to our hospital. All medications were suspended
      because of the possibility of the side effect of drugs. We performed renal biopsy
      and histopathological examination revealed interstitial nephritis and minimal
      change glomerulonephritis. From the result of examination, we considered
      interstitial nephritis was due to rifamicin. The treatment with 50 mg/day of
      prednisolone and isoniazid, ethambutol, and levofloxacin was administrated and
      renal failure and precordial mass were improved. Tuberculous arthritis usually
      affect hip and knee joint and sternoclavicular joint involvement is very rare.

PMID- 19764466
TI  - [A case of disseminated BCG infection found during treatment of an infant with
      Crohn's disease].
AB  - Bloody stools, diarrhea and perianal abscesses were observed from the age of two
      months infant. The boy received a BCG vaccination at the age of four months. The
      patient was diagnosed as having Crohn's disease at the age of six months by
      intestinal endoscopy. Based on the diagnosis, he was treated with nutrition
      therapy, salazosulfapyridine, and prednisolone. Fever of unknown origin occurred
      two months after he had taken azathioprine at the age of two years and two
      months. Mycobacterium tuberculosis was detected from a gastric aspirate, and he
      was diagnosed as having disseminated BCG infection by means of the multiplex PCR
      method. Chest CT showed miliary pulmonary nodules in both lungs on admission.
      Physical examination revealed enlarged lymphnodes, which were palpable around the
      neck and groin, and hepatomegaly. Laboratory data were within normal ranges
      except a slightly increased peripheral white blood cell and serum CRP level. He
      was treated with rifampicin (15 mg/kg/day), isoniazid (15 mg/kg/day) for 12
      months, and streptomycin (25 mg/kg/day) for two months. He became afebrile a week
      after starting the treatment, and the miliary pulmonary nodules in both lungs had
      disappeared by 5 months after starting the treatment. An abnormality of the NEMO
      gene, which is the gene responsible for ectodermal dysplasia and
      immunodeficiency, was identified at the age of three years. It is assumed that an
      abnormality of the NEMO gene caused a latent BCG infection over a period of one
      year and ten months, and immunosuppressive medicine (azathioprine) induced a
      disseminated BCG infection. This case report supports that anti-tuberculosis
      medicine should be given to prevent disseminated BCG infection if an infant who
      receive immunosuppressive therapy is found to have an immune deficiency
      characterized by a mycobacterium infection after BCG vaccination.

PMID- 19764467
TI  - [Tuberculosis of the tongue initially suspected of tongue cancer: a case report-
      including the search for recent 16 cases in Japan].
AB  - A 56-year-old man, having no particular past history, was admitted to our
      hospital, with a 9-month history of painful ulcerated lesion of the tongue and a
      6-month history of productive cough. A physical examination revealed swelling of
      his cervical lymph nodes, and a chest roentgenogram on admission showed cavities
      in the both upper lung fields and nodular shadows over the both lung fields. He
      was initially suspected of having both cancer of the tongue and pulmonary
      tuberculosis, but finally diagnosed as secondary tuberculosis of the tongue due
      to sputum smear-positive pulmonary tuberculosis by biopsy of the tongue and
      sputum examination. He was treated with isoniazid, rifampicin, ethambutol and
      pyrazinamide, and his pain and ulcerated lesion of the tongue rapidly improved.
      Due to our search for recent 16 cases of tuberculosis of the tongue in Japan, we
      found that the patients of tuberculosis of the tongue were more likely to have
      concurrently sputum smear-positive pulmonary tuberculosis. In some cases, the
      delay in diagnosis was seen. These cases suggest that refractory ulcerated cases
      of the tongue should be subjected to the biopsy and examination for acid fast
      bacilli of the tongue with suspicion of tuberculosis of the tongue, and then a
      chest roentgenogram with suspicion of pulmonary tuberculosis.

PMID- 19764468
TI  - [Regulation of neuronal gene expression by DNA topoisomerase IIbeta].

PMID- 19764469
TI  - [Rational and precise design of novel fluorescence probes and their application
      to cellular response and in-vivo tumor imaging].

PMID- 19764470
TI  - [Exploring the "motion" = "function" of the ribosomal A-site molecular switch].

PMID- 19764471
TI  - [Molecular mechanisms for asymmetric cell division in Drosophila neural stem
      cells].

PMID- 19764472
TI  - [Interactions between the microtubule minus-end and cell-cell adhesion
      machinery].

PMID- 19764473
TI  - [Discovery of S1P transporter may uncover the unidentified S1P-regulated signal
      in circulation, immunity, and bone metabolism].

PMID- 19764474
TI  - [Highly unusual non-ribosomal peptide synthetase producing an amino-acid
      homopolymer].

PMID- 19764475
TI  - [Dynamic kinetic resolution of amino acid amides to form chiral amino acids:
      structure and function of alpha-amino-epsilon-caprolactam racemase].

PMID- 19764476
TI  - [Watching "deep breathing motion" of the hydrophobic cavities in a protein
      molecule].

PMID- 19764477
TI  - [Neurotoxicity by microglia: the mechanisms and potential therapeutic strategy].

PMID- 19764478
TI  - [Role of thrombin receptors in vascular physiology and pathophysiology].

PMID- 19764479
TI  - Case of atrial tachycardia originating from giant coronary sinus connected to
      persistent left superior vena cava: successful catheter ablation guided by
      noncontact mapping.
AB  - Radiofrequency (RF) catheter ablation is widely applied to tachyarrhythmia
      associated not only with structurally normal hearts but also with relatively mild
      cardiac anomalies. We present a case of 35 year-old female complaining of
      exercise-induced frequent palpitations caused by atrial tachycardia (AT)
      originating from giant coronary sinus (CS) connected to persistent left superior
      vena cava. AT was sensitive to intravenous ATP administration.
      Electrophysiological study partly using noncontact balloon of EnSite system
      clarified that two foci of AT were located at the orifice and the distal inner
      lumen of giant CS. After repetitive applications of RF energy to these origins,
      AT was not induced by drip infusion of isoproterenol. AT was not evoked by
      exercise without antiarrhythmic drugs 15 months after the RF ablation. This case
      indicates that RF ablation guided by noncontact mapping technique should be
      considered as a therapeutic regimen for AT associated with mild cardiac
      malformations.

PMID- 19764480
TI  - [Influence of serotonin (5-HT) 2A-receptor and transporter (5HTT) gene
      polymorphism upon the effect of olanzapine].
AB  - We investigated the relationship between the genetic polymorphism (s/l) of 5-HT2A
      receptors (A-1438G) and 5-HTT (s/l), and the drug effects among 31 patients who
      are administering olanzapine, as a help of the tailor made medical care in a
      time. As for the genetic polymorphism of 5-HT2AR, G/G group showed a
      significantly improvement tendency in the PANSS positive syndrome score in
      comparison with the group which did not have a G gene (AA and AG). It may be
      possible that this finding help to predict the drugs effect of olanzapine on the
      patients with excite state, who are used many antipsychotics together out of
      necessity.

PMID- 19764481
TI  - [Molecular bases and therapeutic strategies in defective neuromuscular
      transmissions: lessons learned from a prototypical synapse].
AB  - Neuromuscular junction is a prototypical synapse, and most synaptic molecules
      expressed in the central nervous system have been first identified at the
      neuromuscular junction. Congenital myasthenic syndromes are caused by genetic
      defects of molecules expressed at the neuromuscular junction. We have identified
      and characterized five defective molecules. (1) Defects in choline
      acetyltransferase reduce acetylcholine contents at the nerve terminal. (2)
      Collagen Q (ColQ) anchors acetylcholinesterase at the synaptic basal lamina, and
      its defects cause endplate acetylcholinesterase deficiency. ColQ has an anchoring
      signal to the synaptic basal lamina. ColQ expressed in a limited number of muscle
      cells efficiently ameliorates myasthenic symptoms in mice. (3) Loss-of-function
      mutations of acetylcholine receptor (AChR) cause either endplate AChR deficiency
      or fast channel syndrome. Gain-of-function mutations cause slow channel syndrome,
      in which calcium overloading provokes endplate myopathy. (4) Rapsyn clusters AChR
      at the endplate, and its defects cause endplate AChR deficiency. (5) Loss-of
      function mutations of skeletal muscle voltage-gated sodium channel cause
      myasthenia by abrogating the propagation of muscle action potentials. We need to
      further pursue the molecular bases and the therapeutic strategies of defective
      neuromuscular transmissions, and hopefully expand our analysis to defective
      synapse transmissions in the central nervous system.

PMID- 19764482
TI  - [Positron emission tomography: contribution to diagnosis of dementia and
      development of disease-modifying drugs].
AB  - Although there are already many reports about the usefulness of positron emission
      tomography with FDG (FDG-PET) in diagnosis of Alzheimer disease (AD) and
      scientific evidence has been established, further improvement in diagnostic
      ability is achieved by using statistical image analysis, such as SPM and 3D-SSP.
      FDG-PET is also expected to be able to predict conversion to AD in patients with
      mild cognitive impairment (MCI), and establishment of the scientific evidence by
      prospective clinical trial is indispensable. Although clinical application of
      amyloid imaging may enable super-early and pre-clinical diagnoses of AD, many
      unsolved problems still remain. PET can play an important role in clinical trials
      for developing new therapeutic drugs for AD.

PMID- 19764483
TI  - [Role of glutamate transporters in the pathophysiology of major mental
      illnesses].
AB  - Abnormalities in L-glutamate signal transmission have been postulated to play a
      role in major mental illnesses. The glial disruption results in decreased uptake
      of glutamate and an elevation of extracellular glutamate levels. Elevated
      extracellular glutamate may cause cytotoxic damage to neurons and glia.
      Significant down-regulation of glial glutamate transporters, GLT1 and GLAST, in
      major depressive disorder has been reported. In the present study we examined the
      role of glial glutamate transporters in the pathogenesis of autism and
      schizophrenia. We generated animal models in which glutamate receptors are
      overstimulated by genetic down-regulation of glial glutamate transporters.
      Resulting mutant mice showed abnormal social interaction, increased anxiety-like
      behavior, and select phenotypic abnormalities related to the negative and
      cognitive symptoms of schizophrenia. We observed enlarged amygdala and
      hippocampus. These mutant mice replicate many aspects of the behavioral and
      neuroanatomical abnormalities seen in autism and schizophrenia. Thus, these
      mutants are new animal models of major mental illness.

PMID- 19764484
TI  - [M. szulgai developed respiratory failure, after presenting with lower leg
      swelling, skin rash, and multiple lymphadenopathies].

PMID- 19764485
TI  - [Successful treatment of refractory hairy cell leukemia with rituximab].

PMID- 19764486
TI  - [Prolonged hypoglycemia due to insulin auto-antibodies in a maintenance
      hemodialysis patient].

PMID- 19764487
TI  - [Asian variant of intravascular large B-cell lymphoma diagnosed by random skin
      biopsy].

PMID- 19764488
TI  - [Torsade de pointes triggered by high grade fever in patient with LQT2 syndrome].

PMID- 19764489
TI  - [Surgical results of Fontan procedure in hypoplastic left heart syndrome].
AB  - BACKGROUND: We reviewed the preoperative hemodynamic factors, surgical results
      and intermediate outcome of Fontan procedure in hypoplastic left heart syndrome
      (HLHS). METHOD: From 1990 to 2006, 34 patients with HLHS completed Fontan
      procedure in our hospital. We compared preoperative hemodynamic factors, surgical
      results and postoperative course between HLHS group and functional single right
      ventricle (SRV) group who had undergone Fontan procedure. In addition, influence
      of the initial palliation [Norwood procedure with modified Blalock-Taussig (BT)
      shunt, Norwood procedure with right ventricle (RV)-pulmonary artery (PA) conduit
      and bilateral PA banding] to surgical results and postoperative course was
      investigated. RESULTS: The PA index was smaller in HLHS group than SRV group but
      there was no difference in surgical results and intermediate outcome between the
      2 groups. Although age at Fontan was older in Norwood with BT shunt, preoperative
      hemodynamic factors, surgical results and intermediate outcome were similar
      between the 3 groups. CONCLUSION: Although the PA index in HLHS group was small,
      the surgical results of Fontan procedure in HLHS group were comparable with those
      in SRV group. The surgical result of Fontan procedure was satisfactory
      irrespective of the initial palliative procedure.

PMID- 19764490
TI  - [Clinicopathological characteristics of pulmonary cryptococcosis].
AB  - Pulmonary cryptococcosis is a fungal infection caused by the inhalation of
      Cryptococcus neoformans, and may progress to disseminated disease, particularly
      in immunocompromised host such as acquired immunodeficiency syndrome. We reported
      a retrospective review of the 8 patients who had undergone surgical resection for
      pulmonary cryptococcosis during recent 12 years. There were 5 men and 3 women
      with a mean age of 49 years. The number of lesions was solitary in 4 patients and
      multiple in 4 patients. All patients had neither symptom from the lesion nor
      human immunodeficiency virus infection. The most common computed tomography
      finding was well-defined solid nodules (<2 cm) of the lung. The lesion size
      ranged from 0.8 to 2.0 cm with a mean of 1.3 cm. Pathologically, the resected
      specimen revealed Cryptococcus fungal bodies in all cases. After surgery, 4
      patients were treated with systemic antifungal therapy (fluconazole), and the
      others had no treatment. In all patients, no sign of relapse was found during the
      postoperative follow-up period. Although the prognosis of present cases was
      excellent regardless of the treatment after the surgery, the recommendation for
      the treatment in patients with pulmonary cryptococcosis is oral or intravenous
      fluconazole therapy because of the possible development of subclinical systemic
      disseminated disease.

PMID- 19764491
TI  - [Successful mitral valve plasty in a 6-month-old baby suffering from severe
      mitral valve regurgitation].
AB  - A 6-month-old male infant was referred to our hospital with diagnosis of severe
      left heart failure stemming from severe mitral valve regurgitation (MR). He
      showed severe decompensation, and emergency operation was performed.
      Intraoperative transesophageal echocardiogram showed ruptured chordae of the
      posterior leaflet at P1 and P3 sites. The both sites of the posterior leaflet
      were resected and sutured. Bilateral Kay annuloplasty and partial annuloplasty at
      the sites of P1 and P3 were also performed. Postoperative echocardiogram showed
      only trivial MR. He made successful recovery after surgery.

PMID- 19764492
TI  - [Off-pump coronary artery bypass surgery for the ischemic cardiomyopathy patient
      with moderate mitral regurgitation and stenosis of bilateral vertebral arteries].
AB  - We report a 71-year-old man who had severe coronary and cerebral vascular disease
      with moderate mitral regurgitation (MR). Left ventricular reconstruction and
      mitral valve surgery were considered for poor left ventricular function and
      dilatation with MR. However, low blood pressure during cardiac arrest was risk
      for stroke due to severe stenosis of bilateral vertebral arteries. The myocardial
      viability of the anterior wall and inferior wall was confirmed by thallium-201
      rest-redistribution single photon emission computed tomography (SPECT).
      Therefore, off-pump coronary artery bypass grafting (OPCAB) was selected for the
      patient. Only three Lima sutures were used for keeping the optimal heart
      position. Coronary anastomoses were done in sequence right gastroepiploic artery
      (RGEA)-#4 posterior descending (PD), left internal thoracic artery (LITA)-#9-#14
      (sequential), RITA-#8 left anterior descending (LAD). No neurological
      complication occurred postoperatively. Left ventricular function and MR gradually
      improved. Final ejection fraction (EF) is 51% and MR is trivial. This case
      demonstrated improvement of MR by only revascularization according to
      preoperative viability assessment.

PMID- 19764493
TI  - [Thoracoscopic surgery combined with a supraclavicular approach for removing left
      superior mediastinal neurogenic tumor].
AB  - The patient was a 41-year-old female and had been pointed out an abnormal shadow
      at the left lung apex on the chest X-ray film. Chest computed tomography (CT)
      scan and magnetic resonance imaging (MRI) revealed a left upper mediastinal mass
      at the Th1 to Th2 level, measuring 30 mm in size, which was suspected to be a
      neurogenic tumor. Surgical removal of the tumor using thoracoscopic procedure
      through 3 chest ports combined with a supraclavicular approach was successfully
      performed. She was discharged from the hospital on the 7th postoperative day. A
      pathological examination revealed the tumor to be benign neurilemmoma.

PMID- 19764494
TI  - [Treatment of a persistent postoperative chylothorax with octreotide].
AB  - Chylothorax is a serious postoperative complication in the field of thoracic
      surgery. To treat refractory chylothorax, various methods including surgery are
      employed. In this study, we report a patient with refractory chylothorax in whom
      treatment with octreotide acetate was successful, although the chylorrhea site
      could not be determined during additional thoracotomy.

PMID- 19764495
TI  - [Improved cardiac function after inhalation of nitric oxide and tricuspid
      annuloplasty in dilated cardiomyopathy patient on left ventricular assist
      system].
AB  - A 17-year-old man with severe cardiac failure due to dilated cardiomyopathy was
      treated by medication. As he did not improve, he had indication for
      transplantation of the heart and was put on a ventricular assist system as a
      bridge until he could be transplanted. He also had severe tricuspid regurgitation
      and tricuspid annuloplasty was performed. Inhalation of nitric oxide was used to
      decrease pulmonary vascular resistance. Although cerebral infarction was present
      postoperatively, he is waiting for transplant without paralysis. The ventricular
      assist system proved to be useful therapy for serious cardiac failure due to
      terminal dilated cardiomyopathy.

PMID- 19764496
TI  - [Massive hemoptysis after lobectomy for bronchiectasis].
AB  - A 67-years-old female, who was suffered from hemoptysis for about 50 years and
      was diagnosed as bronchiectasis of left lower lobe, was admitted to our hospital
      to receive elective surgical treatment. Left lower lobectomy was performed, and
      on the 10th postoperative day, massive hemoptysis occurred and intratracheal
      hemorrhage caused occlusion of the respiratory tract. Selective bronchial
      arteriogram revealed that bronchial artery of the left upper lobe developed
      remarkably, compared with the findings 1 year ago, and the bleeding site was
      located in the left upper lobe, which seemed to be almost normal before the
      operation. After embolization of this artery the hemoptysis stopped. If bronchial
      artery, which develop well and distribute to the bleeding lobe of the lung, have
      branches to adjacent another lobe, change of blood stream of bronchial artery by
      operation may cause early postoperative recurrence of hemoptysis.

PMID- 19764497
TI  - [Pneumothorax and abdominal free air occurred after percutaneous tracheostomy
      (PCT)].
AB  - We report a case of pneumothorax and abdominal free air after percutaneous
      tracheostomy (PCT). A 80-year-old female was intubation for upper respiratory
      stenosis. We thought tracheal stenosis recurrence after extubation. PCT was
      performed. Respiratory insufficiency and subcutaneous emphysema appeared rapidly
      at face, neck and precordia Subcutaneous emphysema was pushed away. PCT was
      performed once more. Chest X-ray showed pneumothorax in right thoracic cavity.
      Thoracostomy tube was intubation. Chest computed tomography (CT) scan showed
      pneumothorax another thoracic cavity and abdominal free air. Vital signs was not
      worse, so observation. Postoperative course was uneventful. The patient was
      recovered. We thought that PCT was effective under bronchofiber.

PMID- 19764498
TI  - [Pulmonary Mycobacterium avium-intracellulare complex disease that presented
      multiple nodular shadows rapidly].
AB  - The patient was 81-year-old woman diagnosed with lung cancer who underwent upper
      right lobectomy in January 2002. Computed tomography (CT) of the thorax showed a
      mass shadow presenting rapid-growing in the left S3 in August, 2008. The size of
      the mass shadow in the left S3 increased on day 16 after hospitalization, and a
      nodular shadow appeared in the left S(1+2). The bronchial washing specimen showed
      acid-fast bacilli identified as Mycobacterium intracellulare by deoxyribonucleic
      acid (DNA) -DNA hybridization (DDH). The patient showed radiological improvement
      following combination chemotherapy with rifampicin, ethambutol and
      clarithromycin.

PMID- 19764499
TI  - [Evaluation of "Kyobu Geka (the Japanese Journal of Thoracic Surgery)" using
      science database].
AB  - The premiere issue of the Japanese Journal of Thoracic Surgery, known as "Kyobu
      Geka" in Japanese with English abstract, was launched in 1948. Articles of the
      journal become obtainable by PubMed in 1961 (volume 14). In the present study,
      the journal was evaluated using science database, Scopus and PubMed. Jpn J Thorac
      Cardiovasc Surg and Gen Thorac Cardiovasc Surg were used for comparison. A total
      of 7,490 articles published in "Kyobu Geka" by December 2008 were searched. Of
      these, 1,573 articles (21.0%) were cited for a total of 2,548 times. Articles
      cited by non-Japanese papers were mostly of rare case reports and experience of
      use of newly introduced devices. The authors' names and source titles of cited
      articles can be searched easily, and the information obtained is valuable for
      research, writing research grant applications and academic articles. In
      conclusion, although "Kyobu Geka" is published in Japanese, it has been cited by
      many international journals in many languages and, therefore, is making a fine
      performance.

PMID- 19764500
TI  - [Reoperation through right thoracotomy for mitral regurgitation after coronary
      artery bypass grafting; report of a case].
AB  - A 53-year-old male patient developed severe mitral regurgitation 6 years after
      coronary artery bypass grafting (CABG) with a left internal thoracic artery and 2
      saphenous veins. The left ventriculography showed severe mitral regurgitation and
      slight decrease in left ventricular function. The coronary arteriography showed
      all grafts being patent. The median re-sternotomy was avoided because of the risk
      for injury of bypass grafts, and the right anterolateral thoracotomy was chosen.
      Mitral valve replacement was performed under moderate hypothermia and ventricular
      fibrillation without aortic cross clamping. The postoperative course was
      uneventful. Right anterolateral thoracotomy is considered to be a superior
      approach to the mitral valve surgery in the patients with previous CABG.

PMID- 19764501
TI  - [Mitral valve papillary fibroelastoma; report of a case].
AB  - A 65-year-old woman was admitted to our hospital with a diagnosis of cerebral
      infarction. She had incomplete paralysis of the right upper extremity. The
      echocardiogram showed a soft, mobile mass on the atrial side of the mitral
      posterior leaflet. Surgical treatment was performed 3 weeks after the episode of
      cerebral infarction. The mass originated from the P1 portion of the posterior
      leaflet. It was soft and fragile and was carefully resected along with the
      endocardium of the leaflet, from which it arose. The leaflet was reconstructed
      with direct 6-0 proline sutures. There was no mitral insufficiency. The
      histological diagnosis was a papillary fibroelastoma of the mitral valve. The
      postoperative course was uneventful, with no neurologic complications.

PMID- 19764502
TI  - [Acute coronary syndrome caused by giant right coronary artery aneurysm; report
      of a case].
AB  - A 52-year-old man suffered from sudden chest pain. After urgent hospitalization,
      electrocardiogram showed complete atrioventricular (A-V) block. Computed
      tomography and coronary angiography showed a giant right coronary artery
      aneusysm. The patient was reffered to our hospital and elective operation was
      scheduled. The patient was re-attacked by chest pain and A-V block. Emergent
      coronary angiography showed mural thrombus in the right coronary artery aneurysm,
      which apparently caused the acute coronary syndrome. Under extracorporeal
      circulation, ligation of coronary artery aneurysm and coronary artery bypass
      using radial artery graft was performed. The postoperative course was uneventful.
      The histological findings revealed atherosclerotic coronary aneurysm.

PMID- 19764503
TI  - [Thoracic aortic dissection complicating autosomal dominant polycystic kidney
      disease; report of a case].
AB  - A 55-year-old man underwent aortic valve replacement for aortic valve
      insufficiency 12 years ago. At that time, autosomal dominant polycystic kidney
      disease was diagnosed. Subsequently, renal failure developed gradually. In August
      2007, the patient was admitted to the hospital because of dull back pain.
      Computed tomography (CT) revealed aortic dissection extending from the ascending
      aorta to the bifurcation of the iliac artery (Stanford type A). However, the
      patient had no severe symptoms associated with aortic dissection On the basis of
      the results of CT and blood testing, chronic aortic dissection was diagnosed.
      Because the patient also had chronic renal failure we decided to perform elective
      surgery. In January 2008, ascending aortic and aortic arch replacement with a
      distal elephant trunk was performed. After surgery, we were concerned about the
      risk of renal failure. However, the patient recovered uneventfully, without
      requiring dialysis. Aortic dissection can occur as a complication in patients
      with autosomal dominant polycystic kidney. Strict control of blood pressure is
      therefore essential in such patients.

PMID- 19764504
TI  - [Pleuroperitoneal communication at the beginning of continuous ambulatory
      peritoneal dialysis; report of a case].
AB  - A 46-years-old woman admitted for induction of continuous ambulatory peritoneal
      dialysis (CAPD). When peritoneal functional test was performed, dyspnea was
      occurred. Chest X-ray and chest computed tomography (CT) scan revealed massive
      right hydrothorax. Technetium-99m macroaggregated albumin scintigraphy showed
      communication between abdominal cavity and thoracic cavity. The thoracoscopic
      diaphragmal repair was performed. After CAPD was started, right hydrothorax
      occurred again. Re-repair of the diaphragm was performed in small thoracotomy and
      small hole was revealed. The hole was sutured and diaphragm was coverd by fibrin
      glue and polyglycolacid (PGA) felt all over. Since then, CAPD was continued
      successfully. Thoracoscopic surgery is less invasive and appropriate therapy for
      this case. It is important that the diaphragm will be covered all over by fibrin
      glue and PGA sheet because even pin-hole makes recurrence. For detect of the
      communicative portion, use of indigocarmin and examination of glucose
      concentration in the pleural effusion were effective.

PMID- 19764505
TI  - [Pleuroperitoneal communication due to diaphragmatic injury as a complication of
      chest wall resection in a peritoneal dialysis patient; report of a case].
AB  - A 78-year-old female undergoing peritoneal dialysis due to chronic renal failure
      was admitted to our hospital because of a tumor on her right chest wall. The
      diagnosis was recurrence of hepatocellular carcinoma in the thoracic wall, and a
      combined resection of the thoracic wall and diaphragm was performed. Peritoneal
      dialysis was resumed 7 days after surgery, but a right pleural effusion was
      observed after 6 days of dialysis. Surgery was performed because failure of
      sutures related to the excised diaphragm was suspected. A thoracotomy revealed a
      large defect, about 1 cm in size, caused by injury of the diaphragm by an edge of
      the resected rib at the another site of a previous resection of the diaphragm.
      This defect was closed with sutures and the diaphragm was reinforced with a
      polyglycolic acid felt and fibrin glue. Peritoneal dialysis was resumed 7 days
      after surgery and has continued to date without recurrence.

PMID- 19764506
TI  - [The contribution of widely used devices in the diagnosis of peripheral pulmonary
      lesions in patients presenting with respiratory distress].
AB  - PURPOSE: We retrospectively reviewed the contribution of widely used devices such
      as the standard fiberoptic bronchoscope in the diagnosis of peripheral pulmonary
      lesions (PPLs) in patients who presented with respiratory distress. SUBJECT: We
      performed bronchoscopy for 106 PPLs in January-December 2007, and diagnosed
      access to the lesions to be difficult. METHOD: For these lesions, we applied
      Sasada transbronchial angled forceps (STAF), transbronchial needle aspiration
      cytology (TBAC), thin bronchoscopy, and ultra-thin bronchoscopy, which are widely
      used devices, after routinely performing biopsy with standard forceps and saved
      each specimen separately, and finally compared the pathological diagnosis.
      RESULTS: The diagnostic yield obtained with specimens using standard forceps was
      36.8%; however, the overall diagnosis was improved to 70.8% after we used these
      other devices and methods. We achieved diagnosis with STAF (10 lesions), followed
      by thin bronchoscopy (5 lesions), and ultra-thin bronchoscopy (14 lesions). No
      diagnosis was made by TBAC. CONCLUSION: We conclude that these widely employed
      devices can contribute to improvements in the diagnosis of cases of respiratory
      distress in which arrival to the lesions is difficult.

PMID- 19764507
TI  - [Analysis of endobronchial aspergillosis in patients without obvious systemic
      predisposing factors].
AB  - BACKGROUND: Endobronchial aspergillosis is still an insufficiently recognized
      concept. PATIENTS AND METHODS: Ten patients who did not have obvious predisposing
      factors and parenchymal fungal infection were analyzed. They were confirmed to
      have endobronchial Aspergillus by histology and culture, and were classified
      according to the presence of bronchiectasis, allergic reaction, and asthmatic
      symptom. RESULTS: Bronchiectasis was detected in all 10 patients, IgE elevation
      (>370 IU/ml) in 7, Aspergillus specific IgE-RAST in 8, eosinophilia in 7, and
      asthmatic symptom in 5. Cases were classified into allergic bronchopulmonary
      aspergillosis (ABPA) (5 cases), ABPA not fulfilling Rosenberg's criteria (2
      cases), and endobronchial aspergilloma (3 cases). CONCLUSION: We proposed
      classifying endobronchial aspergillosis without obvious systemic predisposing
      factors into "ABPA", "ABPA without asthma", "ABPA-S (seropositive)", and
      "Endobronchial aspergilloma". A fifth subtype of endobronchial aspergillosis
      containing "saprophyte" is warranted.

PMID- 19764508
TI  - [Long-term follow up study of four cases of pulmonary Langerhans' cell
      histiocytosis].
AB  - We reported the clinical features of 4 cases with pulmonary Langerhans' cell
      histiocytosis. All of them were men who had a history of smoking. They ranged in
      age from 23 to 46 years. Cases 1 and 3 did not stop smoking, while Cases 2 and 4
      did stop smoking. All of the chest CTs revealed small nodules and cysts, and
      during the follow-up period of 8 to 13 years, the numbers of nodules decreased
      and the walls of the cysts became thin in all of the cases. Their pulmonary
      function tests revealed restrictive impairment in 3 cases and reduced diffusion
      capacity in 2 cases, but none showed obstructive impairment. FEV1% and DL(CO)
      deteriorated during the follow-up period. Case 1 died of respiratory failure
      after 8 years. Cases 2 and 4 were both alive with home oxygen therapy after 11
      and 12 years, respectively. Case 3 was alive but complained of dyspnea on
      exertion after 13 years. In conclusion, all of the 4 cases showed deterioration
      of pulmonary function, and one of them died due to respiratory failure. The
      prognosis of patients with pulmonary Langerhans' cell histiocytosis appears to be
      poor.

PMID- 19764509
TI  - [A case of pulmonary actinomycosis in which differentiation of primary and
      metastatic lung cancers was difficult].
AB  - The patient was a 72-year-old woman who had undergone low anterior resection for
      T2N1M0 stage IIIA colorectal cancer. A chest X-ray examination was performed 10
      months later for persistent cough, and a solid nodule was found in S5 on the
      mediastinal side of the middle lobe. There were no malignant findings on
      bronchoscopy, but FDG-PET was performed because primary or metastatic lung
      cancers could not be ruled out. High FDG accumulation was detected with an SUV
      value of 13.7, and thus surgical resection was performed for diagnosis and
      treatment. The postoperative diagnosis was pulmonary actinomycosis. Bronchoscopic
      diagnosis of pulmonary actinomycosis has been found to be difficult in many
      reported cases. False positivity of other inflammatory diseases on FDG-PET is
      common, but there are few reports of false positive pulmonary FDG-PET findings in
      actinomycosis. Therefore, pulmonary actinomycosis should be kept in mind for the
      differential diagnosis of cases that are positive in FDG-PET.

PMID- 19764510
TI  - [A case of tumor microembolism diagnosed by perfusion scan and transbronchial
      lung biopsy].
AB  - A 70-year-old woman with breast cancer treated with hormonal therapy had
      progressive shortness of breath for one month. Chest radiograph and computed
      tomography showed mild interstitial changes, but could not account for her
      respiratory failure. Lymphangitic carcinomatosis, drug-induced pneumonitis,
      idiopathic interstitial pneumonitis, opportunistic infection, and pulmonary edema
      were considered in the differential diagnosis of the CT findings. A perfusion
      scan revealed numerous small subsegmental perfusion defects in both lung fields.
      Bronchoalveolar lavage fluid (BALF) contained some cancer cells, suggesting
      lymphangitic carcinomatosis. Transbronchial biopsy (TBLB) specimen showed tumor
      emboli in small pulmonary arteries. Immunohistochemical findings of TBLB specimen
      were consistent with breast cancer cells. A diagnosis of tumor microembolism
      caused by breast cancer metastasis was made. Antemortem diagnosis of tumor
      microembolism is very difficult. Here, we report a case of tumor microembolism
      diagnosed by perfusion scan and TBLB.

PMID- 19764511
TI  - [Allergic bronchopulmonary mycosis induced by Schizophyllum commune--case report
      and review of the literature].
AB  - A 55-year-old man was admitted to our hospital because of pyrexia, cough and
      sputum. He suffered from bronchial asthma. Chest X-ray showed infiltrates in the
      left upper and right lower lung fields. Chest CT scans showed mucoid impaction
      and consolidation predominantly in the left upper lobe. Laboratory tests showed
      peripheral eosinophilia, elevated level of serum IgE, and the increased
      eosinophils in his sputum. Schizophyllum commune was isolated from the
      bronchoscopically-removed mucous plug. A diagnosis of allergic bronchopulmonary
      mycosis (ABPM) due to S. commune was made. Simultaneous daily administration of
      400 mg itraconazole (ITCZ) and corticosteroid (prednisolone; 30 mg daily)
      provided sufficient improvement. However recurrence was recognized on chest CT
      scan findings one year later. There are not enough case reports concerning S.
      commune-induced ABPM to establish a therapeutic approach to the condition.

PMID- 19764512
TI  - [A case of desquamative interstitial pneumonia associated with hepatitis C virus
      infection].
AB  - A 72-year-old-man was admitted to our hospital because of an abnormal chest
      shadow. Histological findings from video-assisted thoracoscopic surgical lung
      biopsy showed desquamative interstitial pneumonia (DIP). Although DIP is
      classified as the idiopathic interstitial pneumonias (IIPs), it is widely
      accepted that the cause of DIP might be associated with cigarette smoking. The
      patient had chronic hepatitis C virus (HCV) infection; however he did not have a
      history of active or passive smoking. An immunologic response to HCV infection
      may have a role in the pathogenesis of DIP in patients with chronic HCV. DIP
      should be included in the differential diagnosis of diffuse parenchymal lung
      disease in patients with HCV infection.

PMID- 19764513
TI  - [A case of Ehlers-Danlos syndrome suspected from pulmonary hematoma due to
      disruption of the lung].
AB  - A 20-year-old man was referred to our hospital due to hemoptysis. Chest CT showed
      a ground-glass opacity, suggesting pulmonary bleeding; however, a diagnosis was
      not obtained. At a follow-up examination after 2 months, Chest CT showed
      improvement of the ground-glass opacity, however a cavitary nodule had newly
      appeared. Four months later, another new nodule was found on chest X-ray film.
      Video-assisted thoracoscopic lung biopsy was performed for pathological
      diagnosis; disruption of the pleural, lung and blood vessels, and pulmonary
      hematoma were found. We thought of the fragility of the pleuro-pulmonary
      connective tissue and also thought of the probability of Ehlers-Danlos syndrome
      (EDS). A biochemical analysis of cultured dermal fibroblasts and molecular
      biological examination revealed decreased production of type III collagen in
      fibroblasts and COL3A1 mutation. We diagnosed this case as vascular EDS. EDS is
      one of the differential diagnoses in patients presenting hemoptysis and pulmonary
      hematoma due to disruption of the lung.

PMID- 19764514
TI  - [A case of hearing loss and diffuse alveolar hemorrhage associated with
      microscopic polyangitis].
AB  - We report a rare case of bilateral hearing loss and diffuse alveolar hemorrhage
      associated with microscopic polyangitis (MPA). A 75-year-old woman complained of
      hearing loss. Two months later, she was admitted due to rapidly progressing
      dyspnea. Chest radiography and CT scan showed diffuse bilateral consolidations.
      Mechanical ventilation was required for respiratory insufficiency. Laboratory
      data demonstrated anemia and renal failure. Steroid pulse therapy and antibiotics
      were initiated. On day 2, bronchoalveolar lavage showed fresh blood-like fluid,
      which suggested diffuse alveolar hemorrhage (DAH). Serum level of myeloperoxidase
      antineutrophil cytoplasmic antibody (MPO-ANCA) was elevated. Therefore, DAH and
      rapidly progressive glomerulonephritis associated with MPA were diagnosed.
      Treatment was also performed with cyclophosphamide pulse therapy and
      plasmapheresis. Her pulmonary lesion improved dramatically. We emphasize the
      effectiveness of bronchoalveolar lavage for prompt and accurate diagnoses.
      Moreover, this case report also suggests that early cyclophosphamide therapy and
      plasmapheresis may be an effective treatment for MPA with diffuse alveolar
      hemorrhage. In contrast, hearing loss did not improve after therapy. Some cases
      reported hearing loss as a rare symptom of MPA. We also suspect that hearing loss
      may be a complication of MPA. We reported this case because there has been no
      description of hearing loss accompanying DAH associated with MPA.

PMID- 19764515
TI  - [A case of Legionnaires' disease with abnormal neurological findings showing the
      corpus callosum abnormality on brain MRI].
AB  - A 47-year-old man was admitted to our hospital because of dysarthric speech and
      high fever. His brain magnetic resonance imaging (MRI) showed high intensity in
      the splenium of the corpus callosum (SCC) on diffusion-weighted and FLAIR
      imaging. His chest CT showed ground-glass attenuation in bilateral lung upper
      lobes, and consolidation in the right lower lobe. Because of his neurological
      findings and radiographic imaging, we started antibiotic therapy using quinolone,
      which is effective for Legionellosis. Later, Legionella species were identified
      by sputum culture. Pneumonia was relieved after antibiotic therapy and in
      parallel with clinical improvement, and the MRI findings also resolved. We report
      a patient who showed abnormal neurological findings and abnormality on brain MRI,
      both of which were reversible, in the setting of acute Legionnaires' disease.

PMID- 19764516
TI  - [A case of severe asthma exacerbation complicated with cerebral edema and diffuse
      multiple cerebral micro-bleeds].
AB  - A 36-year-old woman was admitted to the Intensive Care Unit for the treatment of
      severe asthma exacerbation. Her condition of asthma improved with systemic
      glucocorticosteroids, inhaled beta2-agonist, intravenous theophylline and inhaled
      anesthesia (isoflurane) under mechanical ventilation. Her consciousness was
      disturbed even after terminating isoflurane. Brain CT and MRI scan showed
      cerebral edema and diffuse multiple cerebral micro-bleeds. Glyceol, a
      hyperosmotic diuretic solution consisting of 10% glycerol and 5% fructose in
      saline, was administered to decrease cerebral edema. Her consciousness
      disturbance gradually recovered. Cerebral edema and hemorrhage improved. On the
      69th hospital day, she was discharged from hospital without sequelae. This case
      is a rare one in which severe asthma exacerbation was complicated with cerebral
      edema and diffuse multiple cerebral hemorrhage. Inhaled anesthesia for asthma
      exacerbation should be used carefully to avoid delay of diagnosis of central
      nervous system complications.

PMID- 19764517
TI  - [A case of thoracic empyema caused by Actinomyces species nova].
AB  - A 50-year-old man was referred and admitted to our hospital because of pneumonia
      and pleuritis. The patient had attempted suicide by inhaling automobile exhaust 3
      years ago. Carbon monoxide intoxication had caused persistent disturbance of
      consciousness and quadriplegia. He had been tracheostomised and under nutrition
      by percutaneous endoscopic gastrostomy. On admission the presence of left pleural
      fluid with thickening of the pleura was shown on computed tomography.
      Thoracocentesis produced suppurative fluid with Actinomyces species nova
      identified by the 16S rRNA method. The patient was successfully treated with
      antibiotics and drainage of suppurative fluid.

PMID- 19764518
TI  - [A case of pulmonary Mycobacterium scrofulaceum infection and review of the
      tendency towards recent acid-fast bacilli infection].
AB  - A 47-year-old man presented to a local physician with a chief complaint of sputum
      and cough for 3 months. Chest X-ray showed bilateral consolidation in the upper
      lung fields, and the patient was suspected to have pulmonary tuberculosis: he was
      then referred to our hospital. Smear and culture of both sputum and gastric juice
      showed acid-fast bacilli, and we started administration of rifampicin, isoniazid,
      ethambutol, and pyrazinamide. Results of the culture and identification test
      showed the causative bacillus to be Mycobacterium scrofulaceum (M. scrofulaceum).
      We stopped pyrazinamide and added clarithromycin to the treatment regimen, which
      resulted in symptomatic relief and radiological improvement. The frequency of
      pulmonary nontuberculous mycobacteriosis is increasing: in contrast, pulmonary
      infection by M. scrofulaceum has been decreasing. Nevertheless, M. scrofulaceum
      infection should be considered in the differential diagnosis from tuberculosis
      when the results of radiological findings and sputum culture suggest pulmonary
      tuberculosis.

PMID- 19764519
TI  - [A case of Sjogren syndrome with pulmonary nodular amyloidosis and pulmonary
      multiple cysts].
AB  - A 57-year-old woman who had been given a diagnosis of Sjogren syndrome at age 53
      consulted a nearby doctor because of bloody sputum. He noted her chest abnormal
      shadows and referred her to our hospital. Her chest radiograph and high
      resolution computed tomograph showed multiple nodules and cysts in both lung
      fields. Video-assisted thoracoscopic lung biopsy revealed patchy fibrosis, cystic
      change, AL type amyloid deposition and mild lymphoid hyperplasia and a diagnosis
      of Sjogren syndrome-associated-pulmonary-disease was established.

PMID- 19764520
TI  - [Symptomatic splenomegaly in a young Japanese man with sarcoidosis accompanied by
      spleen, liver, kidney, lung and lymph node lesions].
AB  - A 27-year-old man experienced progressive left hypochondralgia. CT with contrast
      medium enhancement revealed marked splenomegaly, multiple swollen lymph nodes in
      the mediastinum and abdominal cavity, and multiple nodules in the spleen, liver,
      kidneys and lungs. Pathological examinations of the lung and liver lesions showed
      non-caseating granulomatous lesions, and established the diagnosis of
      sarcoidosis. The symptom and lesions presented by CT regressed dramatically with
      administration of corticosteroid (30 mg/day oral prednisolone). Symptomatic
      splenomegaly in a young Japanese man with sarcoidosis seems very rare especially
      considering that sarcoidosis lesions completely regress spontaneously within a
      year in 90% patients of young Japanese men with sarcoidosis.

PMID- 19764521
TI  - [A case of Cushing syndrome presenting after pulmonary nocardiosis with
      pyothorax].
AB  - A 49-year-old woman visited our clinic on July 12th, 2006, complaining of
      discomfort in fingers of both hands, edema of both lower limbs, and pain in the
      right shoulder and chest. Chest X-ray examination showed an infiltrative shadow
      with pleural effusion and loss of lung volume in the left lower lung field. She
      was treated with CTRX, but it was ineffective, and she was therefore admitted to
      Kurume University Hospital on July 21st, 2006. Chest CT demonstrated pyothorax
      and loss of lung volume in the left lung. Culture of a sample obtained by
      thoracentesis yielded Nocardia asteroides. The pulmonary nocardiosis improved
      after oral administration of trimethoprim-sulfamethoxazole, and the patient was
      discharged on August 25th 2006. No immunological impairment was observed, and the
      serum levels of ACHT and cortisol were normal. In February 2007, however, she
      developed facial acne, facial edema ("moon" face), centripetal obesity, and
      weight gain. Cushing syndrome was diagnosed on the basis of tests including a low
      dose dexamethasone suppression test. To the best of our knowledge, there has been
      no previous report of pulmonary nocardiosis with pyothorax in a patient with
      Cushing syndrome. We assume that the present patient had pre-(sub-) clinical
      Cushing syndrome when she presented with pulmonary nocardiosis and pyothorax.

PMID- 19764522
TI  - [Two cases of pleomorphic carcinoma with severe systemic inflammation].
AB  - We report two cases of pleomorphic carcinoma with fever and severe inflammatory
      reaction. In case 1, an abnormal mass shadow was found on the chest X-ray film of
      a 63-year-old man with bloody sputum. After right upper lobectomy, the tumor was
      diagnosed as pleomorphic carcinoma. About 7 months after surgical operation, he
      had fever and chest pain. Although his test results showed leukocytosis and his
      elevated serum CRP level indicated some infection, there were no signs of
      bacterial or fungal infection. Further examination revealed metases of lung
      cancer in the left adrenal gland, mediastinal and iliac lymph nodes. Serological
      study revealed elevated level of G-CSF, likely due to G-CSF producing metastatic
      tumors. In case 2, a 77-year-old man presented with continuous high fever.
      Examinations revealed elevated serum CRP level and multiple nodular shadows and
      enlarged supraclavicular and mediastinal lymph nodes on the chest CT, suggesting
      some infectious, connective tissue, or lymphoproliferative diseases. He was
      finally found to have pleomorphic carcinoma of the lung by histological
      examination of lymph nodes. The continuous high fever seemed to be a tumor
      related fever, because it rapidly disappeared after administration of naproxen.

PMID- 19764523
TI  - [A case of drug-induced interstitial pneumonia due to phenytoin].
AB  - A 48-year-old woman had been given phenytoin for prevention of epilepsy for 30
      years. She developed a dry cough and low grade fever from one year and half
      before admission to our hospital. During this interval, she was treated with
      various antibiotics, however, her condition did not improve. A chest radiograph
      and CT showed diffuse reticular ground glass opacities in bilateral lung fields.
      A drug lymphocyte stimulation test (DLST) for phenytoin showed positive results.
      Lung biopsy specimen by VATS revealed predominant lymphocytic infiltration of
      lung parenchyma, compatible with drug-induced pneumonitis. Administration of
      phenytoin was discontinued, oral administration of 30 mg prednisolone was
      initiated, and the symptoms and shadow on X-ray films improved. These
      observations strongly suggested the presence of drug-induced pneumonia due to
      phenytoin in this patient. In patients who develop pneumonia not associated with
      infection, the possibility of drug-induced pneumonia should be always considered
      even though the drug has been administered for a long period.

PMID- 19764524
TI  - [Where do we go from here? One respiratory physician's perspective].

PMID- 19764525
TI  - [Novel influenza (swine-origin influenza A/H1N1): from the public health view
      points].

PMID- 19764526
TI  - [Social factors influencing the use of medical facilities by infants and their
      parents. A case study of a city near Tokyo].
AB  - OBJECTIVE: This study aimed to demonstrate relationships between frequency of
      visits to medical facilities for infants and factors, including social elements,
      generally thought of as influencing the frequency. METHODS: A questionnaire
      survey was conducted among parents with infants living in a city near Tokyo. The
      subjects comprised 957 residents (97.9% were the mothers) who had infants
      attending nursery schools, kindergartens and/or infant circles. In this city,
      parents can use medical care for infants free of charge, because of subsidies for
      medical costs from the local government. Data for 790 out of the 957 residents
      were adopted for this study. The questionnaire included attributes of infants and
      parents such as age, sex, birth order, parent' employment status and social
      factors such as the availability of childcare support from family or relatives or
      others, attitude of parents to utilization of medical resources, and whether the
      infants concerned had a chronic illness. As the dependent variable, respondents
      were asked about the number of visits to medical facilities by their infants
      during the previous year. The responses to the survey were analyzed by simple and
      multiple regression. RESULTS: In the simple and multiple regression analyses
      (adjusted for infants' age, sex, birth order, parents' employment status),
      statistically significant correlations were found between the number of visits to
      medical facilities and the answers to following questions: whether the infants
      concerned had a chronic illness; the availability of childcare support from
      family or relatives; and the attitude of parents to utilization of medical
      resources. There were no correlations with infants' age, infants' sex, infants'
      birth order, parents' employment status, and the extent of childcare support from
      friends. CONCLUSIONS: The frequency of use of medical facilities by infants is
      negatively associated with social factors such as the availability of childcare
      support from relatives and positively correlated with infants' chronic illness
      and parents' lack of hesitation in using medical services for infants.

PMID- 19764527
TI  - [A questionnaire study of the local community and the food environment for
      children in the Niigata Mid Prefecture Earthquake].

PMID- 19764528
TI  - [Food for children in Niigata Mid-Prefecture Earthquake].

PMID- 19764529
TI  - [Development of a family relationships scale based on the Family Relationships
      Index (FRI) Japanese version].

PMID- 19764530
TI  - [Prognosis of local recurrence after radical cystectomy for bladder cancer].
AB  - The clinical outcome is poor for patients who have local recurrence after radical
      cystectomy for bladder cancer. We investigated clinical outcomes of patients with
      isolated local recurrence and with both local recurrence and distant metastasis.
      From 1990 to 2006, 299 patients who had bladder cancer without distant metastasis
      underwent radical cystectomy in our hospital. We included 200 patients who had a
      negative surgical margin at radical cystectomy and urothelial carcinoma, and who
      had not had upper urinary tract cancer or other active cancer. Fifteen (7.5%) had
      isolated local recurrence (isolated group) and 18 (9.0%) had local recurrence and
      distant metastasis simultaneously (simultaneous group). The median overall
      survival time and that for survival after recurrence were 24 and 13 months,
      respectively, in the isolated group, and 18 and 5 months, respectively, in the
      simultaneous group. Although we did not find a significant difference in overall
      survival (p = 0.314), there was one for survival after recurrence (p = 0.001)
      between the two groups. In the isolated group, 13 died of cancer, 1 of another
      cause and 1 was alive without cancer. All patients in the simultaneous group died
      of cancer. Three patients in the isolated group underwent surgery for residual
      tumors after systemic chemotherapy, and 2 of the 3 survived for more than 2 years
      after recurrence. Some patients with isolated local recurrence benefited from
      multimodal therapies. In these patients, surgery for the residual tumor after
      systemic chemotherapy was likely to be effective if a negative margin was
      achieved in surgical specimens.

PMID- 19764531
TI  - [Factor analysis of the Japanese version of the Aging Males' Symptoms rating
      scale].
AB  - We aimed to validate the Japanese version of the Aging Males' Symptoms rating
      scale (JPN-AMS) by using factor analysis. The study included 155 normal men 40
      years old and older, and 116 patients who visited our clinic with complaints of
      aging males' symptoms. Participants self-administered the JPN-AMS. Factor
      analysis was done to confirm the internal structure of the questionnaire. We
      found three items that were not among the factors in the original Aging Males'
      Symptoms rating scale in normal men and seven items that were not the factors in
      the original scale in the patients who had a serum free testosterone level below
      8.5 pg/ml. In particular, 5 of the 7 somatic items seemed not to be associated
      with the somatic factor. In conclusion, the factor analysis provided a
      confirmation of the internal structure of the JPN-AMS. We have to be aware of the
      different internal structure of the JPN-AMS for the Japanese patients with late
      onset hypogonadism. Therefore, we should take care to use the JPN-AMS, as there
      are cultural differences among countries.

PMID- 19764532
TI  - [Solitary fibrous tumor of the kidney: a case report].
AB  - Solitary fibrous tumor (SFT) of the kidney is rare. A 76-year-old woman was
      referred to our hospital with a complaint of an incidentaloma of the right
      kidney. Computed tomography revealed an ovoid, hypervascular tumor in the right
      kidney. Magnetic resonance imaging showed a low intensity tumor occupying the
      upper calyx of the right kidney (T2 weighted image). Laparoscopic right radical
      nephrectomy was performed. An immunohistochemical study using a monoclonal
      antibody directed against the human hematopoietic progenitor cell antigen (CD34)
      stain confirmed SFT. The follow up at 48 months after surgery showed no
      recurrence or distant metastasis.

PMID- 19764533
TI  - [Two-stage nephron-sparing surgery for bilateral T2 renal cell carcinoma and von
      Hippel-Lindau disease: a case report].
AB  - A 32-year-old man was referred to our hospital for evaluation of bilateral renal
      tumors 8 cm each in diameter. His cousin also had a renal tumor, and she had been
      genetically diagnosed as von Hippel-Lindau (VHL) disease. Bilateral nephron
      sparing surgery was performed in separate stages under clinical diagnosis of
      renal cell carcinoma and VHL disease. Histological examination revealed clear
      cell renal cell carcinoma (pT2). There was no evidence of local recurrence or
      metastasis 6 months after the second operation. In the treatment of renal cell
      carcinoma and VHL disease, nephron-sparing surgery is recommended to achieve a
      disease-free status without renal replacement therapy.

PMID- 19764534
TI  - [A case report of superior mesenteric artery syndrome after hand-assisted
      laparoscopic left nephrectomy].
AB  - A 65-year-old man with left renal cell carcinoma RCC underwent hand-assisted
      laparoscopic nephrectomy. He was discharged on the 8th hospital day, but 2 days
      later he was admitted to the hospital again because of vomiting and abdominal
      pain. Abdominal computed tomography (CT) showed a narrow space between the
      superior mesenteric artery (SMA) and aorta as well as distension of the proximal
      duodenum. Upper gastrointestinal radiographic studies with gastrografin showed
      abrupt vertical cut-off sign of the third part of the duodenum. Therefore, we
      diagnosed SMA syndrome. We started conservative management by nasogastric tube
      and total parenteral nutrition through a central venous line. The patient was
      able to eat on day 24 and was discharged on day 34 after the treatment. SMA
      syndrome is considered as a postoperative complication after abdominal surgery,
      but it is extremely rare. To our knowledge, only 4 cases of SMA syndrome
      following nephrectomy have been reported and this is the first case of SMA
      syndrome following laparoscopic nephrectomy.

PMID- 19764535
TI  - [A case of synchronous contralateral renal cell carcinoma and urothelial
      carcinoma].
AB  - A 63-year-old man was admitted to our hospital with gross hematuria. Abdominal
      computed tomography showed an 80mm right renal tumor, 31mm left renal tumor, and
      30 mm splenic tumor. Cystoscopy revealed a papillary tumor around the left
      orifice. Right radical nephrectomy and splenectomy were performed. Histological
      examination findings showed that the right renal tumor was a renal cell
      carcinoma, clear cell type, G1, INFalpha, pT2, ly0, v0, and that the splenic
      tumor was an arteriovenous fistula. Next, transurethral resection of the bladder
      tumor was performed and a histological examination showed urothelial carcinoma.
      Magnetic resonance imaging indicated that the left renal tumor was a renal pelvic
      cancer. Left total nephroureterectomy and cystectomy were performed, and the
      histological diagnosis was urothelial carcinoma, G3, pT3, ly1, v2. Following the
      operation, hemodialysis was introduced. It is rare for a renal cell carcinoma and
      contralateral renal pelvic cancer to occur simultaneously, as only 15 cases
      including the present have been reported in Japan.

PMID- 19764536
TI  - [Mixed epithelial and stromal tumor of kidney: a case report].
AB  - Mixed epithelial and stromal tumor of kidney (MEST-K) is a rare benign renal
      tumor that was first described by Michal and Syrucek in 1998. Its frequency is
      0.2-0.28% of all the renal tumors. Here, we report an additional case of MEST-K
      occurring in a 28-year-old woman. The patient visited a hospital with complaints
      of lumbago and fever caused by pyelonephritis. The computed tomography revealed
      hydronephrosis and a cystic tumor in the right kidney, and laparoscopic right
      nephrectomy was performed. The resected kidney contained a cystic lesion with a
      grayish-white mural nodule, in the lower portion. The entire lesion measured 5 cm
      in diameter, and the mural nodule 2.5 cm in diameter. Histologically, the cyst
      was lined with tall columnar and transitional epithelia. The mural nodule showed
      microcystic architectures lined with tall columnar and transitional epithelia,
      scattered in a compact stroma. Immunohistochemically, spindle cells in the stroma
      were positive for smooth muscle-specific actin, and estrogen and progesterone
      receptors (ER and PR). Based on these findings, the tumor was diagnosed as MEST
      K. MEST-K was newly introduced to the WHO classification of renal tumors, with a
      pathogenesis related to long-term estrogen exposure, because of ER and PR
      expression in the stroma. It is important to consider the possibility of this
      tumor when encountering cases of cystic tumor in middle-aged and older women, and
      men with a previous history of estrogen administration.

PMID- 19764537
TI  - [Renal artery pseudoaneurysm following retroperitoneal laparoscopic partial
      nephrectomy].
AB  - We report a case of a 59-year-old woman who presented with gross hematuria due to
      development of a pseudoaneurysm that was diagnosed using Doppler ultrasonography
      16 days after retroperitoneoscopic partial nephrectomy for renal cell carcinoma.
      Hematuria resolved after the patient was treated with selective angioembolization
      of the pseudoaneurysm. There has been no recurrence of the pseudoaneurysm for 28
      months after the procedure.

PMID- 19764538
TI  - [Retroperitoneal solitary fibrous tumor: a case report].
AB  - A 63-year-old man with a retroperitoneal tumor found incidentally was referred to
      our hospital. Computed tomography showed a tumor ventrally adjacent to urinary
      bladder and prostate. Pathological examination of retroperitoneal tumor specimens
      obtained by percutaneous needle biopsy revealed hypercellularity of spindle cells
      positive for CD 34. Under the suspicion of solitary fibrous tumor (SFT) or
      stromal tumors of uncertain malignant potential (STUMP), we performed en bloc
      resection of tumor, urinary bladder and prostate because tumor was firmly fixed
      to urinary bladder and prostate. The final diagnosis of retroperitoneal tumor was
      SFT because pathological findings of the surgical specimen were the same as those
      of the biopsy specimens.

PMID- 19764539
TI  - [Laparoscopic right partial nephrectomy in the presence of Riedel's lobe of the
      liver].
AB  - A 54-year-old woman consulted our hospital for further evaluation of an
      incidentally detected small renal mass. Abdominal computed tomography (CT) and
      other imaging showed a right renal mass adjacent to the Riedel's lobe.
      Laparoscopic right partial nephrectomy was performed under a diagnosis of
      suspected renal cell carcinoma. Riedel's lobe is an anatomic variant, which is a
      caudal extension of the right lobe of the liver. Riedel's lobe presented an
      obstruction during right renal surgery, but we performed the procedure
      successfully because we retracted the lobe medially. This procedure yielded a
      clear surgical field, allowing us to perform this delicate operation safely.

PMID- 19764541
TI  - [Two cases of prostatic carcinoma causing a disorder of gastrointestinal transit
      due to rectal stenosis].
AB  - A 64-year-old man, was admitted to the Department of Gastroenterology at another
      hospital in October, 2005 because of constipation and urinary retention.
      Endoscopic and computed tomographic (CT) examinations of biopsy specimens
      obtained from the rectal mucous membrane which appeared to be thickened revealed
      evidence of proctitis but no evidence of malignancy. The patient was referred to
      our hospital because of a high prostate specific anyigen (PSA) level (74.17
      ng/ml), and hydronephrosis accompanied with hydroureter at the right side. Biopsy
      specimens taken from a prostatic tumor through a transrectal route showed
      histological features consistent with anaplastic adenocarcinoma which was
      positively stained with PSA antibody. We treated the patient with maximium
      androgen blackade (MAB), resulting in a decrease in plasma PSA level and
      amelioration of constipation as well. A 77-year-old man, visited a hospital
      because of constipation and high plasma carcinoembryonic antigen and carbohydrate
      antigen (CA) 19-9 values in May, 2005, and was diagnosed as having hyperplastic
      mucous membrane and atypical glands of the rectum by means of a rectal biopsy.
      Having been referred to our hospital, the patient received a prostate biopsy,
      specimens of which revealed moderately differentiated adenocarcinoma with
      negative PSA staining. A pelvic evisceration was performed. The eviscerated
      samples showed no abnormality in the rectal mucous membrane but cancer with light
      PSA staining in the prostatic ducts. The hormone therapy was initiated in the
      patient under the diagnosis of anaplastic cancer in the prostate. Since the
      therapy for the invasion of prostatic cancer on the rectum differs markedly from
      that for a primary tumor in the rectum, it is very important to differentiate
      accurately the one from the other.

PMID- 19764540
TI  - [A case of primary urethral adenocarcinoma accompanied by vaginal wall
      infiltration in which the CA19-9 level was very high].
AB  - A 55-year-old woman had urinary frequency and a constant urge to urinate.
      Computed tomography confirmed a urethral tumor, and transurethral biopsy
      confirmed adenocarcinoma. She visited our hospital to undergo treatment, and we
      performed an anterior pelvic excenteration. On histology, the tumor had spread to
      the bladder, urethra, and vagina. However, the majority of the tumor was located
      in the bladder and urethra, a duct with intestinal metaplasia was present around
      the urethra, and carcinoma in situ was seen in the urethral mucosa. Based on the
      above findings, the patient was diagnosed as having primary urethral
      adenocarcinoma. No tumor cells were seen in the resection stump. Six months after
      surgery, the patient developed bone metastasis, followed by peritoneal and
      pleural dissemination, as well as multiple lung metastases. The patient died nine
      months after surgery. In the present patient, the carbohydrate antigen (CA) 19-9
      level changed with the clinical course, and it was a useful marker. Urethral
      tumor is relatively rare. A urethral tumor accompanied by vaginal wall
      infiltration is likely to be mistaken for a primary vaginal tumor. It was very
      difficult to identify the primary organ in our case. To the best of our
      knowledge, the present patient is the sixth reported case of primary urethral
      carcinoma accompanied by vaginal wall infiltration in Japan. The six reported
      cases are compared and analyzed.

PMID- 19764542
TI  - [A case of osteomyelitis of the pubis after radical prostatectomy: a case
      report].
AB  - A 74-year-old man visited our hospital, because of high prostate specific antigen
      (PSA). Retropubic radical prostatectomy was performed for prostatic cancer.
      Suddenly right inguinal lesion pain appeared at 25 days after operation with
      disturbance of gait. Pelvic magnetic resonance imaging (MRI) demonstrated
      inflammatory change in right pubic bone, pectineal muscle, adductor muscle, which
      suggested the diagnosis of osteomyelitis of the pubis. After long-term
      administration of antibiotic therapy, osteomyelitis of the symphysis pubis and
      gait possible. There was no recurrence of osteomyelitis of the symphysis pubis at
      one year after operation. In addition to our case, we review the 8 cases of
      osteomyelitis of the pubis after radical prostatectomy previously reported in
      Japanese publications.

PMID- 19764543
TI  - [Examination of deglutition during sleep measuring esophageal pressure in sleep
      apnea syndrome patients].
AB  - Why deglutition occurs during sleep remains unclear and controversial, but
      subclinical aspiration during sleep is surmised to contribute to much aspiration
      pneumonia, requiring that deglutition during sleep be evaluated. We studied the
      relationship between deglutition and sleep using deglutition waves based on
      nocturnal polysomnography data recorded while measuring esophageal pressure in
      patients suspected of having sleep-breathing disturbance. Most deglutition was
      found in stage 1 and then in stage 2 and REM sleep. Little deglutition was seen
      in stage 3 and 4, however. A relationship was thus found in sleep phase and
      deglutition, but no clear influence on deglutition during sleep was found for
      sleep apnea syndrome or age.

PMID- 19764544
TI  - [Caloric test in low-tone sensorineural hearing loss].
AB  - Acute low-tone sensorineural hearing loss (ALHL) is generally has a relatively
      good prognosis. We have often found in long-term following-up, however, that ALHL
      relapses, recurs or develops into Meniere's disease. Diagnostic criteria of the
      Acute Altitude Deafness Research Group of the Ministry of Health, Labor, and
      Welfare of Japan, define ALHL as low-tone-disorder sensorineural hearing loss
      without vertigo in which cochlear symptoms -ear fullness, tinnitus, and deafness-
      develop suddenly. Over the last five years, we have treated 31 cases of ALHL, in
      about half of which neurotological examination showed potential peripheral
      vestibular dysfunction on testing positional nystagmus (a) with closed eyes and
      (b) in a dark room with open eyes, and by finding laterality in the peripheral
      labyrinth system on caloric test. These cases show high canal paresis -a maximum
      slow- phase eye velocity of caloric nystagmus exceeding 60%. These results, taken
      together, suggest that derangement extends to the peripheral labyrinth system in
      patients with ALHL.

PMID- 19764545
TI  - [Long-term histological outcome for the larynx after Gore-Tex medialization
      thyroplasty].
AB  - OBJECTIVES: We studied the long-term histological response of the human larynx to
      Gore-Tex implant and evaluated whether its biocompatibility. STUDY DESIGN:
      Retrospective histological study. METHODS: We conducted medialization
      laryngoplasty with expanded polytetrafluoroethylene (ePTEE or Gore-Tex) in a
      patient with vocal-fold paralysis. A strip of Gore-Tex was folded several times
      and inserted into the pocket preserving the inner perichondrium through a thyroid
      cartilage window. The patient died 12 months later and we histologically analyzed
      the larynx. RESULTS: No evidence was seen of foreign body granuloma, migration,
      extrusion, or infection. A modest inflammatory response with a fibrous capsule
      was present around implants. We confirmed the infiltration of abundant collagen
      and numerous fibroblasts into the microporous implant structure. CONCLUSION:
      Histological examination results suggest that Gore-Tex implants are safe and
      biocompatible with the human larynx. A slight inflammatory response and
      infiltration of fibrous tissue into the implant itself demonstrated that Gore-Tex
      implants are immunologically well tolerated.

PMID- 19764546
TI  - [Construction and identification of eukaryotic co-expression plasmid carrying
      FUS1 and recombinant human IL-12 genes and its effection on apoptosis of A549
      cells].
AB  - OBJECTIVE: To construct a eukaryotic co-expression plasmid containing FUS1 and IL
      12, and to investigate the influence of the recombinant plasmid on the cultured
      human lung cancer cell line A549. METHODS: RT-PCR was applied to amplify FUS1
      from MRC-5 cell, the cDNA fragment of IL-12 was derived from pORF-hIL-12 by PCR,
      FUS1 cDNA fragment and IL-12 cDNA fragment were inserted into the multiple
      cloning sites of pVITRO2 to generate the eukaryotic co-expression plasmid pVITRO2
      FUS1-IL-12. The recombinant plasmid was confirmed by restriction endonuclease
      treatment and sequenceing and transfected into A549 cells. The expression of
      genes in pVITRO2-FUS1-IL-12 were identified by RT-PCR, ELISA and Western blot.
      The function of pVITRO2-FUS1-IL-12 inducing the apoptosis of lung cancer was
      identified by Hoechst33258 and flow cytometry. RESULTS: The restriction
      endonuclease digestion and sequencing suggested that co-expression vector pVITRO2
      FUS1-IL-12 was constructed successfully, the expression of FUS1 and IL-12 could
      be detected in A549 cells. The expressions of the two genes in pVITRO2 were not
      affected. The A549 cells transfected with pVITRO2-FUS1-IL-12 exhibited
      significant cell apoptosis. CONCLUSION: The recombinant eukaryotic expression
      vector pVITRO2-FUS1-IL-12 was constructed and expressed in eukaryotic cell
      successfully, which would contribute to a novel and effective treatment
      strategies for combined gene therapy for lung cancer.

PMID- 19764547
TI  - [Construction of eukaryotic expression plasmid for a novel zinc finger protein
      gene Zfp637 and its effect on breast carcinoma cell EMT6].
AB  - OBJECTIVE: To construct the eukaryotic expression plasmid and establish stably
      transfected cell line, which contained the code gene of zinc finger protein637
      (Zfp637), and to observe the effect of Zfp637 gene to the proliferation of tumor
      cells. METHODS: The Zfp637 DNA was amplified from the template of normal spleen
      tissue cDNA and cloned into the eukaryotic expression vector pEGFP-C3. The
      recombinant plasmid, named as pEGFP-Zfp637, was determined by restriction enzyme
      and sequencing analyses. Next the pEGFP-Zfp637 recombinant plasmid was
      transferred into mouse breast carcinoma EMT6 cells with lipofectamine 2000, and
      the stably transfected cells were selected by G418 (named Zfp637-EMT6). The
      growth condition of cells was observed, and subcellular localization of Zfp637
      gene was located by fluorescence microscope at the same time. The Zfp637 mRNA
      expression in the transfected cells was detected by RT-PCR, and the proliferation
      of such cells was measured by MTT. RESULTS: The analysis confirmed that the
      recombinant pEGFP-Zfp637 contained the Zfp637 full-length cDNA. The Zfp637 mRNA
      was over-expressed stably in Zfp637-EMT6. The growth of Zfp637-EMT6 was increased
      obviously when compared with the negative control group and blank group.
      CONCLUSION: The recombinant pEGFP-Zfp637 has been constructed successfully, and
      the expression of the Zfp637 gene can promote the proliferation of cells. This
      recombinant eukaryotic expression plasmid can be used in advanced studies in the
      biological effects of Zfp637 and anti-tumor gene therapy.

PMID- 19764548
TI  - [The construction of recombinant mouse interleukin 4 prokaryotic expressing
      plasmid and the expression and purification of target protein].
AB  - OBJECTIVE: To construct Recombinant Mouse Interleukin 4 prokaryotic expressing
      plasmid, express it in E. coli strain BL21 (DE3), purify and identify the
      expressed cytokine. METHODS: The optimized mIL-4 cDNA fragment was cloned into
      the prokaryotic expressing vector pET-32a (+) to generate pET32/rmIL-4 and
      transformed into BL21 (DE3) cells. After induction, the expressed protein
      wasfound to be in the inclusion of E. coli cells. The induced product was
      purified through Q Sepharose Fast Flow Column and Gel Filtration Column under
      renaturing condition. The purified protein was identified by Western blot
      analysis, and the biologic activity was identified by the generation of mIL-4
      dependence cell CTLL-2 and in vivo experiment of mouse psoriasis model. RESULTS:
      The recombinant plasmid pET32/rmIL-4 has been constructed correctly. The
      inclusion body was washed with 3 mol/L guanidine hydrochloride and denaturized in
      7 mol/L guanidine hydrochloride. Then, the denaturized protein was gradient
      dialysis in the condition of pH 9. 5. The protein we purified has the right
      immunology specificity and biologic activity. CONCLUSION: The recombinant mouse
      interleukin-4 with high purity and biologic activity was prepared in this
      study,which will become the basis for the further study of the biologic activity
      of IL-4.

PMID- 19764549
TI  - [Screening and identification of mesenchymal stem cell strains to secret mouse
      interleukin-12 mediated with lenti-viral vector].
AB  - OBJECTIVE: To screen the stable expression cell strains of mouse interleukin-12
      (mIL-12) from mouse Mesenchymal Stem Cells (mMSCs) transfected with lenti-mIL-12
      virus. METHODS: The mIL-12 cDNA was amplified from plasmid pORF-mIL-12
      (Invivogen) by PCR. The cDNA was subcloned into pENTR 11 to generate recombinant
      plasmid pENTR-mIL-12. Then, pENTR-mIL-12 was homologously recombinated with
      pLenti6/V5-Dest. The recombinant was named as pLenti6/V5-mIL-12 and confirmed by
      PCR and DNA sequencing. The Lenti6/V5-mIL-12 virus was packaged using 293FT
      cells. The Lenti-mIL-12-MSC monoclone was picked from the mMSCs infected by the
      Lenti6/V5-mIL-12 virus using Blasticidin and verified by RT-PCR and ELISA.
      RESULTS: The recombinant pLenti6/V5-mIL-12 was constructed. The sequence of
      amplified mIL-12 gene was consistent with that reported in GenBank. By RT-PCR and
      ELISA, it was confirmed that the mIL-12 protein could be expressed and secreted
      into the supernatant of MSC strain culture. CONCLUSION: The recombinant mMSC
      strains lentivirally engineered to secret mIL-12 were obtained.

PMID- 19764550
TI  - [The effect of Rac1 siRNA on the biological behaviors of gastrointestinal cancer
      cells].
AB  - OBJECTIVE: To explore the effect of Rac1 siRNA on the expression of Rac1 and the
      biological behaviors of gastrointestinal cancer cells. METHODS: Rac1 siRNA was
      transfected into human gastric cancer cell line SGC803 and colorectal cancer cell
      line Lovo by lipofectamine 2000. The expression of Rac1 in these cell lines were
      detected by Western blot and RT-PCR after 48 hours of the transfection. The
      effect of Rac1 on the proliferation of human gastric cancer cell line SGC803 and
      colorectal cancer cell line Lovo were tested by CCK8 kit. The motility of the
      transfected and the control cancer cells were assessed by Wound-healing assay and
      invasion assay. The apoptotic index was evaluated by Hoechst 33258 staining and
      FCM. RESULTS: Rac1 siRNA can down-regulated the expression of Rac1 on human
      gastric cancer cell line SGC803 and colorectal cancer cell line Lovo remarkably,
      and Rac1 siRNA can inhibit both the proliferation and motility of the
      transfectants. Analysis of apoptosis demonstrated that Rac1 siRNA can promote
      apoptosis of the gastric cancer cells and colorectal cancer cells. CONCLUSION:
      Rac1 play an important role in the regulation of biological behaviors of human
      gastric cancer and colorectal cancer cells, and the interference of Rac1
      expression could provide a novel path in reversing the malignant phenotypes of
      these malignancies.

PMID- 19764551
TI  - [Protective effect of hypothermic propofol on ischemic spinal cords].
AB  - OBJECTIVE: To evaluate the protective effect of hypothermic propofol infused via
      the aorta against ischemia/reperfusion injury of spinal cords in rabbits.
      METHODS: Sixty New Zealand white rabbits were randomly divided into six groups
      (n=10 in each group). The infrarenal circum-aortic clamping model was used in
      this study. During the 30-clamping time, 5 mL/kg of normal saline, 10%
      intralipid, propofol, 4 degrees C saline, 4 degrees C intralipid and 4 degrees C
      propofol were infused into the left femoral arteries of the rabbits in group SN,
      IPN, PN, SH, PH and IPH, respectively, at a rate 10 mL/(kg x h). The heart rates,
      blood pressures, respiratory rates and SPO2 were measured during the ischemic
      reperfusion processes. The neurological status (Tarlov Scale system) were
      assessed 6 h, 24 h, and 48 h after the reperfusions. The spinal cords were
      harvested 48 h after the reperfusions for histological analysis. The
      concentrations of excitatory amino (EAA, aspartate and glutamate),
      malondialdehyde (MDA) and superoxide dismutas (SOD) in the harvested spinal cords
      were determined. RESULTS: Group PN, SH, PH and IPH had better neurological
      outcomes and less severe pathological changes than group SN and IPN (P<0.05).
      There were no significant differences between group SN and IPN (P>0.05). Group
      PN, SH, PH and IPH had lower concentrations of EAA in spinal cords than group SN
      and IPN (P<0.05). Group PH had the best neurological outcome, the least
      histopathological changes of spinal cords, and the lowest concentrations of EAA
      (P<0.05). Groups PN and PH had lower concentrations of malondialdehyde than group
      SN, IPN, SH and IPH. Groups PN and PH had higher concentrations of superoxide
      dismutas than group SN, IPN, SH and IPH (P<0.05). CONCLUSION: Both propofol and
      hypothermic liquids can protect spinal cords against ischemia/reperfusion
      injuries. Combined use of propofol and hypothermia results in significant
      recovery of spinal cord functions.

PMID- 19764552
TI  - [The effect or rosiglitazone on signal pathways of transforming growth factor
      beta1 in human lung fibroblast].
AB  - OBJECTIVE: To investigate the expression of CTGF, CTGF mRNA, NF-kappaB and AP-1
      induced by TGF-beta1 in human lung fibroblast (HLF-02), and study the effect and
      possible mechanism of rosiglitazone on signal pathways of TGF-beta1 in HLF-02.
      METHODS: The effects of TGF-beta1, curcumin, PDTC and rosiglitazone on the
      expression of CTGF, NF-kappaB and AP-1 were evaluated with Western blot. The
      expression of CTGF was also detected with immunohistochemistry assay. The level
      of CTGF mRNA was detected with RT-PCR. RESULTS: (1) The CTGF protein levels of
      HLF-02 cells were significantly up-regulated after incubated with 1 ng/mL TGF
      beta1 for 15 min (P<0.01 vs Control). The CTGF mRNA was also up-regulated. The
      levels of CTGF protein and CTGF mRNA expression was up-regulated by TGF-beta1 in
      a time-dependent manner. (2) The expression of NF-kappaB and AP-1 increased after
      HLF-02 cells were incubated with 1 ng/mL TGF-beta1 for 30 min (P<0.01 vs
      Control). The CTGF protein levels were inhibited obviously after HLF-02 cells
      were incubated with PDTC or curcumin. (3) The expression of CTGF, NF-kappaB and
      AP-1 decreased after pre-incubation with different doses of rosiglitazone (P<0.01
      vs TGF-beta1 group). The CTGF mRNA were also markedly inhibited (P<0.01 vs TGF
      beta1 group). CONCLUSION: It is supposed that rosiglitazone inhibits CTGF
      expression induced by TGF-beta1 in HLF-02 cells by activating PPARgamma through
      NF-kappaB and AP-1 signal transduction pathways.

PMID- 19764553
TI  - [Effect of geniposide on vascular dementia in rats].
AB  - OBJECTIVE: To investigate the effect of geniposide on vascular dementia (VaD) in
      rats. METHODS: VaD rat model was established by permanent ligation of bilateral
      common carotid arteries. Morris water maze performance was assessed after 4 weeks
      of treatment with geniposide, followed by pathological examinations of
      hippocampus and cerebral cortex. RESULTS: The VaD rats had significantly longer
      escape latency and lower percentage of activities in platform quadrant than the
      rats in the sham surgery group (P<0.05). The VaD rats treated with geniposide [50
      mg/(kg x d), 75 mg/(kg x d)] had significantly shorter escape latency (except the
      first day of the test) and significantly higher percentage of activities in
      platform quadrant than the VaD rats without treatment (P<0.05). No significant
      differences were found between the geniposide treated group and the Donepezil
      treated group and the sham surgery control group. Geniposide significantly
      alleviated neurons,apoptosis and necrosis induced by chronic cerebral
      hypoperfusion of cortex and hippocampus. CONCLUSION: Chronic cerebral
      hypoperfusion can induce cognitive impairment. Geniposide can improve cognitive
      ability of Vascular Dementia in rats. This may represent a potential treatment
      strategy for vascular dementia.

PMID- 19764554
TI  - [Radix Astragali improves impaired endothelial dependent vasodilation in obese
      rat].
AB  - OBJECTIVE: To investigate the effects of Radix Astragali, a traditional Chinese
      medicine, on endothelium-dependent and non-dependent vasodilation in food-induced
      obese SD rats. METHODS: Fifteen male Sprague-Dawley rats were divided into 3
      groups. The control group (n=5) was fed with normal chow; The obese group (n=5)
      was fed with high fat chow; The Astragali group (n=5) was fed with high fat chow
      and Astragali in drinking water. At the end of six weeks, all rats were killed
      and heart blood samples were taken to assess serum triglyceride, total
      cholesterol, and free fat acid. The thoracic aortas rings were harvested and
      equilibrated in Krebs-Henseleit solution. To measure the endothelium-dependent
      relaxation, the aortas rings were constricted in response to norepinephrine.
      After a stable contraction plateau was reached, cumulative dose-response for
      relaxation to Acetylcholine (10(-8)-10(-4) mol/L) were obtained in each rings.
      Identical experiments were conducted with 10(-8)-10(-4) mol/L sodium
      nitroprusside as the endothelium independent vasorelaxting agent. Responses to
      vasodlilators were expressed as percentage relaxation in all preconstricted
      state. RESULTS: The ratio of celiac fat and body weight in the obese rats was
      higher than in the controls. The levels of serum triglyceride, total cholesterol,
      and free fat acid were elevated in the Obese Group compared with the Control
      Group. The Astragali Group had lower triglyceride and free fat acid levels than
      the Obese Group. Compared with the rats with high-fat diet, the rats fed with
      Astragali lost about 32% of celiac fat. Acetylcholine (10(-8)-10(-4) mol/L)
      caused a concentration-dependent relaxation in all preconstricted aortic rings.
      Compared to the control group, maximal endothelium dependent relaxation in the
      obese group was impaired (P<0.05). In the Astragali group, the relaxation to
      acetylcholine was intermediate between control and obese group (P<0.05). Sodium
      nitroprusside (10(-8)-10(-4) mol/L) induced potent relaxation (endothelium
      independent relaxation) in all rat aortic rings that did not differ statistically
      between groups. CONCLUSION: Astragalus has salutary effects on impaired
      endothelial dysfunction in the context of obesity.

PMID- 19764555
TI  - [Effect of Adiponectin on endothelial dysfunction in obese rats].
AB  - OBJECTIVE: To test the effect of Adiponectin on endothelium-dependent and non
      dependent vasodilation in food-induced obese SD rats. METHODS: Ten male Sprague
      Dawley rats were divided into 2 groups: the rats in the control group (n=5) were
      fed with normal chow; The rats in the experimental group were fed with high fat
      chow (n=5). At the end of the sixth week, all rats were killed and the thoracic
      aortas were harvested. The vessel rings obtained from the obese rats were pre
      incubated for 2 hours with adiponectin, or adiponectin plus L-NAME, or none of
      them, then equilibrated in Krebs-Henseleit solutions. Constriction of the vessel
      rings were induced by norepinephrine followed by relaxations with increasing
      doses of acetylcholine (for endothelium dependent vasodilatation, EDV) or sodium
      nitroprusside (for endothelium independent vasodilation, EIV). Vasorelaxation was
      expressed as percentage of residual of maximal contraction. RESULTS:
      Acetylcholine (10(-8)-10(-4) mol/L) caused a concentration-dependent relaxation
      in all preconstricted aortic rings. Compared with the control group, the maximal
      endothelium dependent relaxation of the aortic rings in the obese rats was
      impaired (p<0.05). With Adiponectin, the relaxation response of aortic rings to
      acetylcholine improved (P<0.05). Sodium nitroprusside (10(-8)-10(-4) mol/L)
      induced relaxation (endothelium independent relaxation) did not differ
      statistically between the two groups. CONCLUSION: Impaired endothelium-dependent
      vasodilatation has been observed in food-induced obese rats and Adiponectin can
      improve the endothelial dysfunction in obese rats.

PMID- 19764556
TI  - [Effects of enteral nutrition and parenteral nutrition on gut epithelial tight
      junction and barrier function in rats after surgical stress].
AB  - OBJECTIVE: To compare the effects of enteral nutrition (EN) and parenteral
      nutrition (PN) on gut mucosal barrier function and intestinal epithelial tight
      junctions in rats after surgical stress. METHODS: Fifty SD rats with surgical
      trauma were randomly divided into three groups: total parenteral nutrition (TPN)
      group and enteral nutrition (EN) group with isocaloric and isonitrogenous
      nutrition and placebo group. Nutrients were administered via the neck vein and
      needle jejunostomy for the TPN group. The homogenated tissues of liver, lung, and
      mesenteric lymph nodes were cultured to determine the bacterial translocations
      rates. The transmembrane binding proteins (occludin) were measured with
      immunohistochemistry. The ultrastructure and morphology of intestinal epithelial
      tight junctions were observed by electron microscope. The feces in cecum were
      cultured for anaerobic bacterial growth analyses. RESULTS: The EN group had more
      lactobacteria and bifydobacteria than the TPN group, but not statistical
      significant. The EN group had greater expression of occludin in the intestines
      than the TPN group. Furthermore, the intestinal epithelial tight junction and
      microvilli of the EN group were more intact compared with those of the TPN group.
      The bacterial translocations rates of liver, lung and mesenteric lymph nodes were
      significantly lower in the EN group than in the TPN group. CONCLUSION: Neither EN
      nor standard PN maintains intestinal membrane barriers. But EN increases the
      expression of transmember binding proteins, maintains the gut epithelial tight
      junction, improves intestinal mucosal barrier and reduces gut bacterial
      translocation.

PMID- 19764557
TI  - [Effect of polycythemia on hypoxia induced pulmonary hypertension and pulmonary
      vascular remodeling in rats].
AB  - OBJECTIVE: To investigate the effect of polycythemia on hypoxia induced pulmonary
      hypertension and pulmonary vascular remodeling in rats. METHODS: The healthy
      female Sprague-Dawley rats were randomly divided into 3 groups: normoxia control
      group (C group), hypoxia group (H group), hypoxia + different doses of human
      recombine hemopoietin (rEPO) group. All rats in hyoxia groups were exposed to
      hypoxia, 8 hours every day, for 21 days. The rEPO groups were injected sc with
      different doses of rEPO (300 U/kg, 600 U/kg, 900 U/kg, 1200 U/kg) thrice weekly.
      Blood samples were taken for the measurement of RBC, Hb, Hct, plasma EPO
      concentration, whole blood/plasma viscosities, the animals were then catheterized
      to record mean pulmonary arterial pressure (mPAP) and demised to calculate the
      ratio [RV/(LV+S)]. Percentage of vascular wall thickness and muscularization of
      non-muscular pulmonary arteriole were examined microscopically. RESULTS: (1) As
      the dosage of exogenous rEPO increased, blood concentration of EPO increased
      correspondingly, as RBC, Hb, Hct and whole blood/plasma viscosities increased in
      various degrees. (2) There was positive correlation between whole blood viscosity
      and Hct at both high and low shears and linear correlation between mPAP and whole
      blood viscosity at high shear. (3) The degree of pulmonary hypertension,
      reflected by mPAP increased in accordance to rEPO dosage increment. However, the
      extent of pulmonary vascular remodeling alleviated somehow as the rEPO dose
      increased and so did right ventricular hypertrophy. CONCLUSION: Polycythemia
      induced by exogenous EPO increases the blood viscosity and the pulmonary vascular
      resistance, which contributes to the formation of hypoxia induced pulmonary
      hypertension.

PMID- 19764558
TI  - [Association of oxidative stress and serum adiponectin in patients with metabolic
      syndrome].
AB  - OBJECTIVE: To analyze the correlation between oxidative stress and serum
      adiponectin in patients with metabolic syndrome (MS). METHODS: A total of 126
      patients with metabolic syndrome were recruited in the study, and 98 healthy
      physical examinees with normal serum glucose, lipids, liver function and kidney
      function were matched with the patients in age and sex and served as controls.
      The serum total adiponectin(Total-Ad), high molecular weight adiponectin (HMW-Ad)
      and indexes of oxidative stress [reduced glutathione (GSH), oxidized glutathione
      (GSSG) and malondialdehyde (MDA)] of the participants were determined. The
      correlations between adiponectin (Total-Ad and HMW-Ad) and the indexes of
      oxidative stress in the patients and the controls were determinaed by multiple
      linear regressions. RESULTS: Compared with the controls, the patients had
      decreased Total-Ad [(3.51+/-0.83) microg/mL vs (4.34+/-0.98) microg/mL], HMW-Ad
      [(1.32+/-0.42) microg/mL vs (2.15+/-0.85) microg/mL] and GSH [(1.15+/-0.54)
      micromol/L vs (1.96+/-0.62) micromol/L], and increased GSSG [(1.20+/-0.47)
      micromol/L vs (0.90+/-0.23) micromol/L] and MDA [(6.92+/-1.50) nmol/L vs (4.05+/
      0.65) nmol/L] (P<0.05). For the patients, total-Ad and HMW-Ad were positively
      correlated with GSH, with a partial correlation coefficient of 0.587 and 0.480
      respectively (P<0.05), and negatively correlated with MDA, with a partial
      correlation coefficient of -0.222 and -0.389 respectively (P<0.05). For the
      controls, no correlations between adiponectin and oxidative stress indexes were
      found (P<0.05). CONCLUSION: Oxidative stress accompanies MS patients. Adiponectin
      has a better correlation with GSH than the other indexes, which can serve as an
      index of oxidative stress. Hypoadiponectinemia correlates closely with oxidative
      stress in patients with MS.

PMID- 19764559
TI  - [In vitro study of expression and effects of HSP70/HSP90 in nasopharyngeal
      carcinoma cells after thermotherapy].
AB  - OBJECTIVE: To investigate the changes and effects of HSP70/HSP90 of in
      nasopharyngeal carcinoma cells HNE1 after thermotherapy. METHODS: HNE1 cells were
      incubated at 42 degrees C for 2 h. The changes of mRNA and protein level of
      HSP70/HSP90 were detected by real-time PCR and western-blot at different
      intervals. HNE1 cells were pretreated with quercetin, geldanamycin or quercetin
      plus geldanamycin, respectively, before heat treatment. Flow cytometry assay was
      applied to determine the apoptosis of HNE1 cells before thermotherapy and at 2 h,
      4 h, 6 h, 8 h, 12 h and 24 h after thermotherapy. RESULTS: HSP70/HSP90 expression
      was up regulated at 2 h, reached to its peak at 4 h, descended at 8 h and
      returned to the normal level at 24 h after thermotherapy. The inhibition of HSP70
      through quercetin induced up-regulation and delayed descent of HSP90. Combined
      pretreatment with quercetin and geldanamycin could significantly induce HNE1
      apoptosis when compared with pretreatment with quercetin or geldanamycin alone
      (P<0.05). CONCLUSION: HSP70/HSP90 expression in HNE1 up regulated promptly after
      thermotherapy. Inhibition of expression and activity of HSP70/HSP90 before
      thermotherapy can increase sensitivity of the tumor cell to heat treatment.

PMID- 19764560
TI  - [Effect of irradiation on matrix metalloproteinases, vascular endothelial growth
      factor and microvessel density of mice bearing Lewis lung cancer].
AB  - OBJECTIVE: To investigate the effect of irradiation on matrix metalloproteinases
      (MMPs), vascular endothelial growth factor (VEGF) and microvessel density (MVD),
      which influence on tumor growth and metastases of mice bearing Lewis lung cancer
      (LLC). METHODS: C57BL/6 mice bearing LLC were randomized into two groups to
      receive radiation and no-radiation, respectively. When tumor reached about 190
      mm3 in volume on the fourteenth day after inoculation, the radiation group was
      irradiated to the primary tumor (6MV-X, 5 Gy/day, d14, 16, 18, 20). On the eighth
      day after irradiation, animals were killed to examine primary tumors, normal
      tissue near tumors. MMP-2, MMP-9, VEGF and MVD were checked by
      immunohistochemical means. RESULTS: Immunohistochemical examination demonstrated
      an increased expression of MMP2, MMP9, VEGF and MVD in the tumor tissue of the
      radiation group (P<0.05). Additionally, the expression levels of MMP2 and MMP9 in
      the tumor tissue were higher than those in the normal tissue near tumor (P<0.05).
      CONCLUSION: This study showed that irradiation might increased MMP2, MMP9, VEGF
      and MVD expression in the tumor tissue of mice bearing Lewis lung cancer. Our
      finding supports a potential way to overcome tumor metastasis induced by
      radiation if MMP inhibitor and anti-vascularization are combined to irradiation
      clinically.

PMID- 19764561
TI  - [Effects of ERK and STAT3 on cell signal transduction in alveolar epithelium A549
      cells stimulated by mechanical force].
AB  - OBJECTIVE: To observe the effect of mechanical force on the expression of p-ERK
      and p-STAT3 when pulmonary epithelium A549 cells were subjected to tensile
      stress. METHODS: By the self-made four-point bending system, the A549 cells were
      subjected to cyclic tensile stress of 3000 microstrain for 30 min, 1 h, 2 h or 4
      h respectively, then the total protein of each time point was collected and the
      expression of p-ERK and p-STAT3 were detected by Western blot analysis. RESULTS:
      (1) The expression of p-ERK was activated at 1 h and remained at a high level
      until 4 h. (2) The expression of p-STAT3 (Ser) was activated at 30 min and
      remained at a high level until 4 h. CONCLUSION: Tensile stress can activate the
      expression of p-ERK and p-STAT3 (Ser) in alveolar epithelium A549 cells. ERK and
      STAT3 may participate in the cell mechanotransduction in A549 cells.

PMID- 19764562
TI  - [The expressions and clinical significance of IGFBP-2, -3 in both serum and tumor
      tissues in patients with epithelial ovarian cancer].
AB  - OBJECTIVE: To explore the serum levels of IGFBP-2, -3 and their proper roles in
      the regulation of IGF-II bioavailability in patients with ovarian tumor, and to
      investigate the correlation between the expressions of IGFBP-2 and IGFBP-3 in
      ovarian tumor tissues and related clinicopathological characteristics. METHODS:
      Serum levels of IGFBP-2, -3 and big/mature IGF-II were measured by Western ligand
      blot (WLB) and Western blot (WB) in patients with ovarian tumor (10 cases of
      benign tumor, 6 cases of borderline tumor and 10 cases of malignant tumor) and 10
      cases of normal control. The expressions of IGFBP-2 and IGFBP-3 were examined in
      39 specimens of ovarian tumor (8 cases of benign tumor, 8 cases of borderline
      tumor and 23 cases of malignant tumor) and 4 cases of normal ovarian tissues by
      immunohistochemical staining. RESULTS: The serum levels of both big and mature
      IGF-II in epithelial ovarian cancer (ovarian cancer) patients were significantly
      decreased compared with those of normal control and benign and borderline tumor
      (P<0.001 or P<0.01). The increased serum level of IGFBP-2 and decreased IGFBP-3
      level were observed in patients with malignant ovarian tumors by comparing with
      those of patients with normal controls, benign and borderline tumor (P<0.001 or
      P<0.01). The expression of IGFBP-2 was significantly higher in malignant ovarian
      tumor tissues than those in normal control and benign ovarian tumors tissues
      (P<0.0001, P<0.001, and the expression of IGFBP-3 decreased significantly in
      lower differentiated ovarian cancer tissues compared with that in high and
      moderate differentiated ovarian cancer tissues (P<0. 05). CONCLUION: IGFBP-2
      predominantly presents in the circulation of malignant patients in contrast to
      IGFBP-3, which may result in altered bioavailability of IGF-II in ovarian cancer,
      leading to the progress of tumor. The serum levels of both IGFBP-2 and IGFBP-3
      and their expressions in tumor tissues are correlated with the
      clinicopathological characteristics of ovarian cancer patients. Our findings
      suggest that the presence of new mechanisms in the regulation of IGF-II
      bioavailability, and provide the evidence for the possibility to use IGFBP
      2/IGFBP-3 as biological markers in diagnosis and prognosis of ovarian cancer.

PMID- 19764563
TI  - [The relationship between PTEN expression and PI3K/AKT signal pathway in colon
      carcinoma].
AB  - OBJECTIVE: To investigate the expression of PTEN in carcinogenesis and
      development of colon carcinoma and to reveal their correlation with the PI3K/AKT
      pathway. METHODS: The expressions of PTEN and p-AKT were detected by
      immunohistochemistry and western blotting in 32 specimens from patients with
      colon carcinoma. RESULTS: The positive rate of p-PTEN was significantly lower in
      colon carcinoma (31.25%) than that in normal control tissues (96.87%, P<0.01),
      and the positive rate of p-AKT was significantly higher in colon carcinoma
      (87.5%) than that in normal control tissues (15.62%, P<0.01), and expression
      level of PTEN and p-AKT were related to histological differentiation, distant
      invasion, lymph node metastasis and Duke's stage (P<0.05). A negative correlation
      was observed between the expression of PTEN and p-AKT proteins. (r=-0.872,
      P<0.01). CONCLUSION: The over-expression of AKT accompanied by the loss of PTEN
      involves carcinogenesis and development of colon carcinoma.

PMID- 19764564
TI  - [Effects of CO2 and 5% dextrose solution on expression of CD44 and ICAM-1 in
      endometrial carcinoma cells].
AB  - OBJECTIVE: To investigate the effects of 5% dextrose solution and different CO2
      pressures on expression of adhesion molecules (including CD44 and ICAM-1) of
      endometrial carcinoma cells in vitro. To provide experimental base for the safety
      question of hysteroscope operation and the selection of better distending medium
      for the patients with suspected endometrial cancer. METHODS: Endometrial cancer
      cells (HEC-1-B) were put in 5% dextrose, 70 mmHg 100% CO2, 100 mmHg 100% CO2 at
      37 degrees C, the control group was not given any administration, respectively
      for 1 hour. Expression of CD44 and ICAM-1 were measured at 0, 12, 24, 48 and 72
      hours by using flow cytometry. RESULTS: The expression of CD44 and ICAM-1
      increased significantly at 0 h-72 h after the cells were exposed to 5% dextrose,
      70 mmHg 100% CO2, 100 mmHg 100% CO2 for 1 hour (P<0.05) respectively, and
      returned to the control levels by 72 h. With the increase of the CO2 pressure,
      the expression of the CD44 and ICAM-1 increased (P<0.05). The expression of the
      CD44 and ICAM-1 totally increased significantly compared with control.
      CONCLUSION: Both high pressure CO2 (100 mmHg) and 5% dextrose solution can
      increase the expression of CD44 and ICAM-1 in endometrial cancer cells, and may
      promote the capability of adhesion of endometrial cancer cells. Lower CO2
      pressure does not change the expression of CD44 and ICAM-1 in endometrial cancer
      cells, therefore the low CO2 pressure (70 mmHg) is safer as distending medium for
      the patients with suspected endometrial cancer.

PMID- 19764565
TI  - [AQP4 expression in the brains of patients with glioblastoma and its association
      with brain edema].
AB  - OBJECTIVE: To investigate the expression of aquaporin-4 (AQP4) in the brains of
      patients with glioblastoma and its association with brain edema. METHODS:
      Immunofluorescence cytochemistry and western blot tests were performed to detect
      the expression of AQP4 in the brain tumors and the adjacent tissues in 30
      patients with glioblastoma. The association between AQP4 and the extent of brain
      edema was analysed. RESULTS: The AQP4 immunoreactive cells were mainly astrocytes
      in the brains, which were extensively distributed in the intracytoplasm. Higher
      expressions of AQP4 were found in the brain tumors and adjacent tissues in the
      patients with glioblastoma than in the normal controls (P<0.05). More AQP4 were
      distributed in the tumor adjacent tissues than in the tumors (P<0.05). The AQP4
      was positively correlated with the extent of brain edema. CONCLUSION: AQP4
      overexpress in the brain tumors and adjacent tissues, which is associated with
      the extent of brain edema. Cytotoxic and vasogenic edemas may coexist in the
      cerebral edema induced by glioblastoma.

PMID- 19764566
TI  - [Expression of HSP60, TLR4 and NF-kappaBp65 in the peripheral blood of patients
      with atopic dermatitis].
AB  - OBJECTIVE: To investigate the expressions of HSP60, TLR4 and NF-kappaBp65 in the
      peripheral blood of patients with atopic dermatitis (AD) and their roles in the
      pathogenesis of AD. METHODS: RT-PCR, immunocytochemistry and ELISA were performed
      to measure the mRNA expressions of TLR4 and NF-kappaBp65 in the peripheral
      lymphocytes and monocytes, and the serum HSP60, respectively. A total of 17
      patients with AD were recruited for the study, with 15 healthy people serving as
      controls. RESULTS: The levels of HSP60, TLR4 mRNA and NF-kappaBp65 were
      significantly higher in the peripheral blood of the patients with AD than in the
      controls (P<0.05). CONCLUSION: HSP60, TLR4 and NF-kappaBp65 are overexpressed in
      the peripheral blood of patients with AD, which might be associated with the
      pathogenesis of AD.

PMID- 19764567
TI  - [Role of collagen III, CTGF and TNF-alpha in premature rupture of human fetal
      membranes].
AB  - OBJECTIVE: To detect the expression of collagen III, CTGF and TNF-alpha in human
      fetal membranes with premature rupture of fetal membranes (PROM) and non-PROM,
      and explore their roles in the pathogenesis of PROM. METHODS: Fifty women with
      PROM were enrolled in this study, and divided into preterm premature rupture of
      membranes (pPROM, n=24) and term premature rupture of membranes (tPROM, n=26)
      according to gestational age. Fifty non-PROM pregnancies matching the same
      gestational age were recruited as control group. Collagen III CTGF and TNF-alpha
      in fetal membranes were detected immunohistochemically and analyzed by computer
      image analysis system. Linear correlation analysis was used to determine the
      relationship between collagen III, CTGF and TNF-alpha. RESULTS: (1) The
      expression of collagen III and CTGF in pPROM group (88.81+/-5.25, 85.45+/-6.91)
      and tPROM group (94.53+/-6.43, 88.15+/-4.93) were decreased significantly
      (P<0.05, P<0.01) when compared to their control groups (preterm labor 95.99+/
      8.41, 90.30+/-5.74, normal term delivery 100.80+/-9.77, 93.20+/-5.33); The
      expression of collagen III in pPROM group appeared significantly decrease when
      compared to that in tPROM group (P<0.01). The expression of TNF-alpha in pPROM
      group (98. 23+/-8.35) and tPROM group (107.85+/-8.68) were increased
      significantly (P<0.01) when compared to their control groups (preterm labor
      83.82+/-6.03, normal term delivery84.50+/-6.14); The expression of TNF-alpha in
      pPROM group was decreased but not significantly when compared to that in tPROM
      group (P>0.05). (2) The expression level of Collagen III was positively
      correlated with that of CTGF in pPROM group (r=0.838, P=0.001), but no
      correlation was found in tPROM group. Collagen III was negatively correlated with
      TNF-alpha in both pPROM (r=-0.689, P=0.002) and tPROM group (r=-0. 655, P=0.001).
      CONCLUSION: Abnormal collagen development caused by CTGF and excess apoptosis of
      membrane cell caused by TNF-alpha are related to the occurrence of pPROM.
      However, the basic reason of abnormal collagen resulted in tPROM group is not
      from CTGF, it may be related with the degeneration of fetal membrane and the TNF
      alpha-induced excess cell apoptosis.

PMID- 19764568
TI  - [Expression of acid-sensing ion channels in neurons of trapezoid body and lateral
      paragigantocellular nuclei in rat brain, and effects of intermittent hypoxia on
      their expression].
AB  - OBJECTIVE: To investigate the expression of three acid-sensing ion channel (ASIC)
      subtypes termed as ASIC1b, ASIC2a, and ASIC3 in the neurons of trapezoid body and
      lateral paragigantocellular nucleus of rat brainstem, and the effects of
      intermittent hypoxia on their expression. METHODS: The intermittent hypoxic rat
      model was established, of which the blood gas analysis was tested after 12 days.
      The immunohistochemistry SABC method was performed to test the expression of
      ASIC1b, ASIC2a, and ASIC3 in neurons of trapezoid body and lateral
      paragigantocellular nucleus in the control (O2) and intermittent hypoxic (IH)
      groups of rats. RESULTS: The ASIC1b-, ASIC2a- and ASIC3-positive immunoreactive
      neurons all could be observed in the nucleus of trapezoid body and lateral
      paragigantocellular nucleus. The intermittent hypoxia group, the numerical
      density of ASIC1b-positive immunoreactive neurons (cell/mm3) decreased in the
      nucleus of trapezoid body (P<0.05), but did not significantly change in the
      lateral paragigantocellular nucleus (P>0.05), the grey level did not
      significantly change in both the nucleus of trapezoid body and lateral
      paragigantocellular nucleus (P>0.05); the numerical density of ASIC2a-positive
      immunoreactive neurons (cell/mm3) did not significantly change in the nucleus of
      trapezoid body and lateral paragigantocellular nucleus (P>0.05), the grey level
      in the nucleus of trapezoid body increased (P<0.05) while it did not
      significantly change in the lateral paragigantocellular nucleus (P>0.05); the
      numerical density of ASIC3-positive immunoreactive neurons (cell/mm3) decreased
      in the lateral paragigantocellular nucleus (P<0.05), but it did not significantly
      change in the nucleus of trapezoid body (P>0.05), the grey level did not
      significantly change in the nucleus of trapezoid body and lateral
      paragigantocellular nucleus (P>0.05). CONCLUSION: The ASIC1b, ASIC2a, and ASIC3
      exist in the neurons of trapezoid body and lateral paragigantocellular nucleus in
      the rat brainstem under normal condition, and their expressions in the two nuclei
      are different to intermittent hypoxia, which means that the roles of subtype of
      ASICs in different area may be different in the respiratory effects induced by
      hypoxia.

PMID- 19764569
TI  - [Cigarette smoke-induced oxidative damage to human bronchial epithelial cells].
AB  - OBJECTIVE: To determine the oxidative damage of mainstream smoke (MS) on Human
      bronchial epithelial cells (HBE) and its role in lung cancer. METHODS: MTT assay
      was used to test the cytotoxicity of MS on HBE. The HBE cells were treated with
      different concentrations of MS for 12 h. The chromatosome damage and DNA strand
      breaks were measured by micronucleus test and alkaline comet assay respectively.
      The contents of ROS in the HBE cells were determined using fluorescence method.
      RESULTS: With the increase of MS, the viability of HBE cells decreased. The IC50
      decreased with the increasing exposure time to MS, showing significant dose
      effect and time-effect relationships. The MS induced DNA strand break in the HBE
      cells. The comet, L Tail, Tail DNA and OTM increased with the increase of MS
      concentrations. Cigarette smoke also induced chromosome damage. The micronucleus
      rate of the HBE cells exposed to more than one cigarette/L of MS was
      significantly greater than the controls (P<0.05). The ROS increased with the
      concentration of MS. CONCLUSION: MS induces ROS in HBE cells, resulting in
      increased cytotoxicity, chromosome damage and DNA strand breaks, which suggests
      that oxidative damage is an important mechanism of lung cancer caused by MS.

PMID- 19764570
TI  - [Effects of cyclic mechanical stretch on the activity of STAT3 in human bronchial
      epithelial cell (16HBEC)].
AB  - OBJECTIVE: To study the effects of cyclic mechanical stretch on the activity and
      expression of STAT3 in Human bronchial epithelial Cell (16HBEC). METHODS: The
      16HBECs were subjected to cyclic mechanical stretch by the four-point bending
      system at 0.5 Hz of 1 kPa, 2 kPa, 3 kPa, 4 kPa for 30 min or for 30 min, 1 h, 3
      h, and 6 h of 3 kPa respectively. The mRNA level of STAT3 was semi-quantified by
      RT-PCR; STAT3 protein and phosphorylated STAT3 were detected by western blot.
      RESULTS: Phosphorylation level of STAT3 Tyr705 was higher under 3 kPa cyclic
      mechanical stretch than the others. 3 kPa stretch phosphorylatd STAT3 Tyr705 in
      16HBE cells in a time-dependent manner. The phosphorylation of STAT3-Tyr705 was
      significantly increased at 30 min compared with the control group (P<0.05), and
      reached the highest phosphorylation level at 1 h, then showed a sharp descending
      tendency. There was no effect of 3 kPa stretch on the phosphorylation of STAT3
      Ser727, expression of STAT3 protein or mRNA levels. CONCLUSION: STAT3 played an
      important role in the response and signal transduction of 16HBECs to the cyclic
      mechanical stretch stimulation through the phosphorylation of STAT3 Tyr705.

PMID- 19764571
TI  - [The expression level of NGF, BDNF and NT-3 in spinal cord of growing embryonic
      chicken].
AB  - OBJECTIVE: To study the expression of NGF, BDNF and NT-3 in spinal cord of
      growing embryonic chicken. METHODS: The lumbar segments of the spinal cords were
      obtained from chick embryos at 7 day (E7) and 14 day (E14) respectively. The
      distribution of nerve growth factor (NGF), brain-derived neurotrophic factor
      (BDNF) and neurotrophin-3 (NT-3) was examined in frozen sections by
      immunohistochemistry, and their level was determined by Western blot. RESULTS: At
      E7, intensive NGF was detected mainly in the white matter of ventralateral zone,
      and BDNF was seen in both perikaryon and neurite of neurons, in the gray matter
      of the ventral horn, while NT-3 existed mainly within parts of the ventrolateral
      region of the spinal cord. Comparatively, at E14, NGF increased apparently in
      both the white and the gray matter. And BDNF presents in neuronal cell bodies and
      some axon of the dorsal horn, while NT-3 positive neurons were detected in the
      intermediate zone and the dorsal horn. Western-blot analysis confirmed the level
      of NGF, BDNF and NT-3 were all up regulated from E7 to E14 in the spinal cord of
      embryonic chicken during development. CONCLUSION: The increase of NGF, BDNF and
      NT-3 in the dorsal horn was concomitant with the development of spinal cord from
      E7 to E14, suggesting that NGF, BDNF and NT-3 may be associated with the growth
      of the spinal cord during development.

PMID- 19764572
TI  - [Effects of wild type PTEN gene on proliferation, apoptosis and the influence on
      apoptosis key factor Bcl-2 and Caspase family on K562 cells].
AB  - OBJECTIVE: To investigate the effect of tumor-suppressing gene,wild type PTEN
      gene, mediated by adenovirus vector on the cell proliferation, apoptosis and the
      influence on apoptosis key factor Bcl-2 and Caspase family on human chronic
      myeloid leukemia (CML) cell line K562 in vitro. METHODS: The recombinated Ad-PTEN
      gene containing green fluorescent protein gene (Ad-PTEN-GFP) or the empty vector
      (Ad-GFP) was transfected into K562 cells. The growth of K562 cells was evaluated
      by MTT assay; the transfection efficiency of Ad-PTEN-GFP, apoptosis rate and
      proliferation index (PI) were assessed by flow cytometry (FCM). Morphological
      characteristics of transfected cells under light and transmission electron
      microscope were applied to demonstrated the apoptosis; DNA ladder and fluorescent
      staining were also tested; the PTEN, Bcl-2 mRNA levels were detected by real-time
      fluorescent relative-quantification reverse transcriptional PCR (FQ-PCR); PTEN
      and Bcl-2 protein levels were detected by Western Blotting; and Caspase-3/7 and 
      9 protein activity were detected by corresponding kits. RESULTS: The 200
      multiplicity of infection (MOI) of Ad-PTEN-GFP was applied to transfect K562
      cells. The maximum growth inhibiting ratio was 37.1%. The early and advanced
      apoptosis rates were higher than Ad-GFP group and untransfected group (P<0.05).
      After 3 days transfaction of PTEN gene the Bcl-2 mRNA and protein were 0.27 fold
      and 0.58 fold respectively; and the Caspase-3/7 and -9 protein activity increased
      in time-depentend manner after transfected with PTEN gene at the first 3 days
      compared with Ad-GFP group and untransfected group. CONCLUSION: Over expression
      of PTEN gene can inhibit K562 cells proliferation and promote cell apoptosis
      probability via inhibiting Bcl-2 expression and up-regulating the Caspase-3/7 and
      -9 ability.

PMID- 19764573
TI  - [Effects of cholesterol ester transfer protein taqIB polymorphism on changes of
      serum lipid ratios induced by high-carbohydrate/low-fat diet in healthy youth].
AB  - OBJECTIVE: To investigate the effects of cholesterol ester transfer protein gene
      (CETP) TaqIB polymorphism on serum lipid ratios and their responses to high
      carbohydrate/low-fat (HC/LF) diet in healthy youth. METHODS: After on regular
      diet for 7 days, 56 health youth [(22.89+/-1.80) years] were given HC/LF diet for
      6 days. The regular diet contained 54% carbohydrate, 15% protein, and 31% fat of
      the total energy. The LF/HC diet contained 70% carbohydrate, 15% protein, and 15%
      fat of the total energy. The serum lipids were measured on the 1st, the 8th and
      the 14th day. The ratios of TG/HDL-C, log (TG/HDL-C), TC/HDL-C, and LDL-C/HDL-C
      were calculated. The polymorphism of CETP was analyzed by PCR-RFLP method.
      RESULTS: No significant difference was found of the lipid ratios at baseline in
      subjects with different genotypes in both genders. After the regular diet, TC/HDL
      C was significantly lower in males carrying the B2 allele than B1B1 homozygotes
      (P<0.05). After HC/LF diet, no significant difference was found of the lipid
      ratios between the subjects with different genotypes in the whole study
      population or in males and females separately. Compared with those before HC/LF
      diet, subjects with B1B1 genotype experienced significant changes of the four
      lipid ratios after HC/LF diet (P<0.05), while the B2 carriers had only
      significant decrease of TC/HDL-C and LDL-C/HDL-C (P<0.05). No significant
      difference of the changes of the four lipid ratios before and after HC/LF diet
      was found between the subjects with different genotypes. When gender was taken
      into account, significant increases of TG/HDL-C and log (TG/HDL-C) were found in
      females with B1B1 genotype (P<0.05). All the subjects experienced significant
      decrease of TC/HDL-C and LDL-C/HDL-C regardless of gender and genotype (P<0.05).
      As for the changes of lipid ratios before and after HC/LF diet, difference of
      only TC/HDL-C was found between males with B1B1 and male carriers of B2 (P<0.05).
      CONCLUSION: Polymorphism of CETP TaqIB may influence the response of TC/HDL-C to
      HC/LF diet in males and the increases of TG/HDL-C and log (TG/HDL-C) induced by
      HC/LF diet in females.

PMID- 19764574
TI  - [Clinical pharmacokinetics/pharmacodynamics study on pazufloxacin
      methanesulphonate injection].
AB  - OBJECTIVE: To identify rational dosage regimen for pazufloxacin methanesulphonate
      injection through a pharmacokinetics/pharmacodynamics (PK/PD) study. METHODS:
      Pazufloxacin methanesulphonate at the doses of 300 mg and 500 mg were injected to
      24 healthy volunteers. The plasma concentrations of pazufloxacin were measured by
      RPHPLC-UV. The MICs of pazufloxacin against 130 strains of 7 species of
      bacterias, as well as the MPCs of pazufloxacin against 5 species of bacterias
      were measured by double broth dilution method. RESULTS: The AUC0-24/MIC50 of
      pazufloxacin methanesulphonate at a stabilized concentration state against
      methicillin-sensitive Staphylococcus aureus (MSSA) and S. pneumoniae were 215.36
      and 107.68 at the dose of 300 mg, and 309.60 and 154.80 at the dose of 500 mg,
      respectively. The Cmax/MIC50 were 57.52 and 28.76 at the dose of 300 mg, and
      81.28 and 40.64 at the dose of 500 mg, respectively. However, the AUC0-24/MIC of
      pazufloxacin methanesulphonate against methicillin-resistant staphylococcus
      aureus (MRSA) were far less than 40. Both the AUC0-24/MIC50 and the Cmax/MIC50 of
      pazufloxacin against P. aeruginosa at the doses of 300 mg and 500 mg exceeded the
      defined criteria 100 and 10. Whereas the AUC0-24/MIC and Cmax/MIC of pazufloxacin
      against E. coli, K. pneumoniae and A. baumanii were much less than 100 and 10.
      The capability of pazufloxacin methanesulphonate to prevent mutations of MSSA was
      strong at the dose of 500 mg, but not for other pathogenic bacteria either at 300
      mg or 500 mg. CONCLUSION: Pazufloxacin methanesulphonate at the dose of 300 mg
      and 500 mg have similar efficacy in treating acute bacterial infections. The
      dosage regimen of 300 mg Q12h intravenous infusion is recommended.

PMID- 19764575
TI  - [Antihypertensive effect and pharmacokinetics of low molecular mass potassium
      alginate].
AB  - OBJECTIVE: To investigate the effect of low molecular weight potassium alginate
      (L-PA) on blood pressures in spontaneously hypertensive rats (SHRs) and its
      pharmacokinetics characteristics in mice. METHODS: The systolic blood pressure
      (SBP) was measured by tail-cuff method in conscious SHRs. Forty rats were
      randomly assigned to the following five groups: control, hydrochlorothiazide
      (HCT, 6.25 mg/kg), L-PA in low, middle or high dose groups (100, 250, 500 mg/kg).
      SHRs were intragastrically (i. g.) administrated once daily for 28 days. The SBP
      was measured once weekly during drug treatment, and 3 and 6 days after drug with
      drawal. KM mice were i. g. administered with 100 mg/kg (74 MBq/kg) of 3H-L-PA.
      Ten microl blood samples were obtained from the tail vein at 2, 5, 10, 20, 30 min
      and 1, 2, 4, 6, 12, 24, 48, 72, 96, 120 or 144 h after drug administration for
      measuring radioactivities. Pharmacokinetics parameters of the oral administration
      of L-PA were analysed with DAS 2.0 software. RESULTS: Twenty-one or 28 days after
      administration, the rats in the groups treated with HCT or L-PA at 100, 250 or
      500 mg/kg had a significant decrease in SBP (P<0.01 vs control group). Three or 6
      days after drug withdrawal, the antihypertensive effect of HCT disappeared
      (P>0.05), whereas the rats treated with 250 or 500 mg/kg L-PA still had lower SBP
      than the controls (P<0.01). The L-PA at a dose of 100 mg/kg also led to a
      significant decrease in SBP 3 days after drug withdrawal (P<0.05). The
      pharmacokinetics of L-PA (i. g.) was consistent with a two-compartment model,
      with 2.76 h of absorption half-life (t1/2, Ka), 42. 30 h of distributional half
      life (t1/2alpha), 42. 31 h of elimination half-life (t1/2beta), and 36.28 h of
      terminal phase elimination half-life (t1/2z). CONCLUSION: Oral administration of
      L-PA has significant anti-hypertensive effect, which can be maintained to 6 days
      after drug withdrawal. The sustaining anti-hypertensive effect of L-PA is
      probably associated with its slow elimination in vivo.

PMID- 19764576
TI  - [SKLB-102 inhibits acute hepatitis induced by concanavalin A in mice].
AB  - OBJECTIVE: To test the effect of 5-(4-methoxybenzylidene)-2-thioxo
      dihydropyrimidine-4, 6 (1H, 5H)-dione (SKLB-102) on acute hepatic inflammatory
      induced by concanavalin A (ConA) in mice. METHODS: The inhibitive effect of SKLB
      102 on RAW264.7 cell migration induced by recombinant rat monocyte chemotactic
      protein-1 (MCP-1) was tested. The serum from the ConA-treated mice was collected
      after intragastric administration of SKLB-102 at the dose of 50 mg/kg bodyweight.
      The serum AST and ALT were determined by an automatic analyzer, and the serum TNF
      alpha was determined with enzyme-linked immunosorbent assay (ELISA) kits. The
      liver samples were fixed in 10% formalin, embedded in paraffin, sectioned and
      then stained with hematoxylin and eosin for histological examinations. RESULTS:
      SKLB-102 markedly reduced cell migrations, successfully reduced serum AST, ALT
      and down-regulated TNF-alpha. CONCLUSION: SKLB-102 is likely to suppress the
      occurrence of Con A-induced hepatitis by suppressing macrophages migration and
      TNF-alpha releases.

PMID- 19764577
TI  - [Effects of diaryliodonium on the properties of light-curing composite resin].
AB  - OBJECTIVE: To test the effects of two kinds of diaryliodonium on the degree of
      conversion (DC), the compressive strength (CS) and the cure depth (CD) of the
      light-curing composite resin. METHODS: BisS-GMA was used as reisin matrix, with
      TEGDMA as diluent and SiO2 as inorganic filler. CQ, DMAEMA and two different
      kinds of diaryliodonium (diphenyliodonium hexafluorophosphate and bis (p-tolyl)
      iodonium hexafluorophosphate) were used as photoinitiator, respectively. The DC,
      CS, CD were measured and compared by the FTIR spectroscopy, and the tensile
      strength of machine et al. RESULTS: Diaryliodonium led to greater DC, CS, and CD
      of the light-curing composite resin. The DC, CS, and CD of the light-curing
      composite resin increased more with bis (p-tolyl) iodonium hexafluorophosphate
      than with diphenyliodonium hexafluorophosphate. CONCLUSION: Diaryliodonium can
      improve the DC, CS, and CD properties of light-curing composite resin. Bis (p
      tolyl) iodonium hexafluorophosphate has better performance than diphenyliodonium
      hexafluorophosphate in improving photosensibility and solubility of the
      photoinitiator system.

PMID- 19764578
TI  - [Glycemic excursions in people with normal glucose tolerance in Chengdu].
AB  - OBJECTIVE: To investigate the characteristics of glycemic excursions in people
      with normal glucose tolerance (NGT) in Chengdu. METHODS: A total of 50 non-obese
      people with normal glucose tolerance (NGT, 23-68 years old), normal blood
      pressures and lipid profiles participated in the study. The fluctuations of
      glucose levels in the participants were measured by a continuous glucose
      monitoring system (CGMS) for three days 72 h. The 48 h mean blood glucose (MBG),
      mean amplitude of glycemic excursions (MAGE), Largest amplitude of glycemic
      excursions (LAGE), Postprandial peak glucose (PPG), Postprandial glucose
      excursion (PPGE), Mean of postprandial glucose excursion (MPPGE), and absolute
      means of daily differences (MODD) were measured. RESULTS: The number of glucose
      values detected by CGMS amounted to 861+/-7 with a mean absolute difference (MAD)
      of 11.3%+/-10.6%. The CGMS values were significantly correlated with the
      capillary glucose measurements (n=1076, r=0.761, P<0.005). The participants had a
      MBG of (5.9+/-1.2) mmol/L, a MAGE of (1.7+/-0.7) mmol/L, a LAGE of (4.4+/-1.9)
      mmol/L, a daily glycemic peak (PPG) of (8.7+/-1.7) mmol/L, a nadir level of
      (4.3+/-0.7) mmol/L, a MPPGE of (2.3+/-1.6) mmol/L, and a MODD of (0.75+/-0.79)
      mmol/L. The post-breakfast Postprandial glycemic excursions (PPGE) were lower
      than those of post-lunch and post-dinner (P=0.01 and P=0.05). The postprandial
      glucose excursions in the 60-70 year-old participants were the highest (P<0.022).
      In 95% (77%-100%) of the daytime, the glycose levels fluctuated between 4.1 and
      8.8 mmol/L, and 78% of the participants (n=39) had hyperglycemia (BG>7.8 mmol/L)
      and 10% (n=5) had asymtomatic hypoglycemia (BG<2.8 mmol/L). CONCLUSION: CGMS
      tests may be important for detecting asymptomatic hyperglycemia and hypoglycemia.
      The NGT people in Chengdu have exhibited abnormal blood glucose values in CGMS,
      revealing problems in people with normal range of blood glucose.

PMID- 19764579
TI  - [Brain evoked potentials in patients with depression or anxiety].
AB  - OBJECTIVE: To investigate the features and clinical implications of event related
      potential (ERP) and cognitive-processing in patients with depression, anxiety or
      both anxiety and depression METHODS: A total of 34 patients with anxiety
      (HAMA>14, HAMD<17), 33 patients with depression (HAMD>17, HAMA<14), 54 patients
      with both anxiety and depression (HAMA>14, HAMD>17), and 37 health volunteers
      were recruited in the study. The event related potential were recorded by Nihon
      Kohden instruments. RESULTS: Compared with the healthy volunteers, the latency of
      P3a and P3b was longer (P<0.05) and the amplitude of N2-P3b was lower in the
      patients with anxiety (P<0.05); the Amplitude of N2-P3b was lower (P<0.05) in the
      patients with depression; the latency of P3a was longer and the amplitude of N2
      P3b was lower (P<0.05) in the patients with both anxiety and depression. The
      latencies of P3a and P3b in the patients with anxiety and both anxiety and
      depression were longer than in the patients with depression(P<0.05). The latency
      of N2 in the patients with anxiety and depression was longer than in the patients
      with anxiety or depression (P<0.05). CONCLUSION: The features of ERP in patients
      with depression are different from those with anxiety, which provides an
      electroneurophysiology basis for the clinical diagnosis and differential
      diagnosis for anxiety and depression.

PMID- 19764580
TI  - [The mental health of children and adolescents from earthquake affected areas].
AB  - OBJECTIVE: To examine the mental health status of 11-16 years old children
      exposed to the 5.12 WenChuan earthquake and to help develop post-traumatic
      psychological interventions. METHODS: The self-reported Strengths and
      Difficulties Questionnaire (SDQ) was administered to 540 children (mean age:
      13.82+/-0.98, male/female ratio 1.06:1) from the earthquake affected areas one
      month after the earthquake. RESULTS: (1) The children had an average difficulty
      score (T score) of 13.41+/-5.71, with 74.6% reporting at least minor perceived
      difficulties. (2) The children with higher levels of exposure had higher
      emotional subscale scores (z=-2.323, P=0.020). The female students had higher
      emotional subscale scores than the male students (z=-4.985, P=0.000). (4) The
      impact of the difficulties on the children's learning increased with age
      (z=9.106, P=0.011). (5) The longer the children lived in the transferred safe
      places, the more likely the children got an abnormal (OR=1.233, P=0.003).
      CONCLUSION: The mental health status of the children from the earthquake affected
      areas are influenced by their exposure levels, gender, age and the length of
      living in transferred safe places. These factors should be taken into
      considerations when post-traumatic psychological interventions are planned.

PMID- 19764581
TI  - [Carrying rate of Neissria meningitides in a healthy population in the Mianzhu
      post-earthquake residential area].
AB  - OBJECTIVE: To predict the possibility of epidemic outbreak of meningitis by
      testing Neissria Meningitides in a healthy population in the Mianzhu post
      earthquake residential area. METHODS: A simple random sampling strategy was
      adopted to collect 887 throat swabs from a healthy population in the Mainzhu post
      earthquake residential area. The TaqMan assay were performed to detect Neissria
      Meningitides. RESULTS: Three positive samples were identified. CONCLUSION: The
      carrying rate of Neissria Meningitides is not high enough to bring about an
      epidemic outbreak of Meningitis. However, efforts to maintain a hygienic
      environment in the post-earthquake residential area should be continued.

PMID- 19764582
TI  - [Effects of the different culture and isolation methods on the growth,
      proliferation and biology characteristics of rat bone marrow mesenchymal stem
      cells].
AB  - OBJECTIVE: To explore a suitable method for isolation, purification and
      multiplication of bone marrow mesenchymal stem cells (BMSCs). METHODS: Density
      gradient centrifugation and adherence separation methods were applied for
      isolation of BMSCs from Wistar rats. The cells were cultured and proliferated in
      culture medium containing calf serum (CS), fetal bovine serum (FBS), free of
      serum or different volume fraction of FBS. The characteristic and the morphology
      of BMSCs were observed under inverted microscope every day. The growth curves
      were draw and the surface antigen of BMSCs were detected by immunocytochemistry
      technique. The microstructure was observed by transmission electron microscope
      (TEM). RESULTS: The pure primary cells can be procured by density gradient
      centrifugation. But the primary cells cultured by adherence separation methods
      demonstrated higher cytoactive, more rapid proliferation, earlier colony
      confluence and shorter time for passage than that cultured by density gradient
      centrifugation method. The cells by adherence separation methods were essentially
      purified at passage 4. Both CS and FBS can promote the growth and proliferation
      of BMSCs, but the colony forming efficacy of cells (46.50%) cultured in medium
      containing 0.12 volume fraction FBS was the highest. The cells surface markers
      CD44, CD90 were positive and CD14, CD45 were negative. BMSCs were observed by TEM
      and possessed the characteristic of stem cells. Conclusion BMSCs with high
      quality and activity can be obtained with adherence separation by suitable method
      and culture conditions. L-DMEM medium containing 0.12 volume fraction FBS showed
      more profitable for the growth and proliferation of BMSCs.

PMID- 19764583
TI  - [Preparation and characterization of artemether-iron sucrose lipid
      nanoparticles].
AB  - OBJECTIVE: To prepare Artemether-Iron Sucrose lipid nanoparticles and examine the
      characteristics of the nanoparticles. METHODS: The Artemether-Iron Sucrose lipid
      nanoparticles were prepared by film-dispersing and high-pressure homegenization
      technique using soybean phospholipid and soybean oil as matrix. The entrapment
      efficiency and drug loading capacity were determined by HPLC. The morphology was
      examined by transmission electron microscope and the mean particle size was
      measured by laser light scattering technique. RESULTS: The products were
      spherical and well distributed. The mean diameter was (161+/-17.4) nm with
      (85.1+/-0.83)% of entrapment efficiency and (5.3+/-0.2)% of drug loading. The in
      vitro release test showed that the Art-IS-NLC had good sustained release
      characteristics. CONCLUSION: The preparation method of Art-IS-NLC is simple and
      feasible. The products are well distributed with a high entrapment efficiency.

PMID- 19764584
TI  - [Preparation and application of biotinylated anti-AIB1 moniclonal antibody].
AB  - OBJECTIVE: To cross-link the McAb 1A2E1 to BNHS reagents and apply this
      biotinylated McAb to detect AIB1 antigen of target cells. METHODS: The McAb 1A2E1
      was mixed with BNHS reagents to generate Biotin-1A2E1. The competitive inhibition
      ELISA and immunocytochemical method were applied to detect the biologic activity
      of antibody. RESULTS: The antibody kept high biological activities (with a titer
      of 1 : 3200) and sensitivities in detecting the AIB1 protein of breast cancer
      cell. CONCLUSION: The method of preparing biotinylated McAb is successful, and
      the prepared biotinylated McAb can be applied to detect target cells which
      express AIB1 antigen. This McAb provide useful tool for tumor auxiliary
      diagnosis.

PMID- 19764585
TI  - [Determination of lovastatin and its active metabolites in human plasma with high
      performance liquid chromatography-tandem mass spectrometry].
AB  - OBJECTIVE: To develop a sensitive LC-MS/MS method for analyzing lovastatin and
      its active metabolites lovastatin acid in human plasma. METHODS: Lovastatin and
      lovastatin acid were extracted from plasma by ethyl ether -dichloromethane (V/V,
      1:1), with simvastatin serving as an internal standard. The analytes went through
      the column of Phenomenex Gemini C18 (50 x 3 mm, 3 microm) with mobile phase
      acetonitrile-water (85:15), and was analyzed by API3000 after protonated with ESI
      mode. The ion pairs being detected were 427.4-->325.4, 445.4-->343.4 and 436.4-
      >325.4, respectively. RESULTS: The established method was able to determine
      lovastatin in human plasma over the range of 0.03125-64 microg/L, with recovery
      rates ranging from 96% to 102%. The intra and inter day variances were below
      9.3%. CONCLUSION: The LC-MS/MS method for analyzing lovastatin is validated and
      is suitable for clinical pharmacokinetic studies.

PMID- 19764586
TI  - Middle ear tuberculosis: diagnostic criteria.
AB  - INTRODUCTION: Tuberculous otitis is a diagnostic problem due to the difficulty to
      obtain microbiological, histomorphological and cytological confirmation of the
      disease. OBJECTIVE: Our objective was to compare clinical and radiological
      characteristic and development of otogenic complications in patients with
      tuberculous otitis and otitis with cholesteatoma as the most destructive form of
      chronic nonspecific otitis in the purpose of establishing the diagnostic criteria
      for tuberculous otitis. METHODS: Medical records of 12 patients with tuberculous
      otitis and 163 patients with cholesteatoma treated at the Institute of
      Otorhinolaryngology and Maxillofacial Surgery in Belgrade during the eight-year
      period were analyzed. All of the patients underwent otomicroscopic, audiological
      and radiological examination of the thorax and temporal bone, microbiological
      examination of the secretion and histomorphological examination of the tissue
      taken during middle ear surgery. Statistical analysis was done using chi2 test
      with Yates correction. RESULTS: Otogenic complication as facial palsy and
      sensorineural hearing loss were more frequent in tuberculous otitis patients,
      than in cholesteatoma. Also, fistulas of the labyrinth and facial canal bone
      destruction were also more frequent in tuberculous otitis than in cholesteatoma.
      A larger extent of temporal bone destruction was noticed on CT scans of the
      temporal bone in half of the patents with tuberculous otitis. Coexistence with
      miliary pulmonary tuberculosis was detected in one third of the patients. There
      were no microbiological or histomorphological confirmations of the disease,
      except in one case with positive ZiehI-Neelsen staining. CONCLUSION: Tuberculous
      otitis media should be considered in patients with serious otogenic complications
      and with shorter duration of ear discharge, and in association with diagnosed
      miliary pulmonary tuberculosis and extensive temporal bone destruction.
      Polymerase chain reaction still is not reliable for diagnosis.

PMID- 19764587
TI  - [Possibilities of endodontic therapy of endodonic-periodontal lesions].
AB  - INTRODUCTION: Endoperiodontal lesions are frequent in clinical practice and may
      require complex therapy. It is very important to determine differential diagnosis
      and the origin of the lesion, because the treatment plan is based on aetiology
      and stadium of the development of the lesion. OBJECTIVE: The aim of this clinical
      study was to analyze the efficacy of endodontic treatment in different types of
      endodontic-periodontal lesions. METHODS: Thirty patients and 42 teeth with
      diagnosed endoperiodontal lesions were included in the study and divided in two
      groups. Vital pulp therapy was applied to 18 vital teeth where the diagnosis was
      perio-endodontic lesions. The therapy of infected canal system was applied to 24
      teeth with endodontic-periodontal or combined lesions. Standard endodontic
      procedure consisted of cleaning and shaping of the root canal system and between
      sessions filling with calcium-hydroxide paste. Obturation was made by lateral
      compact of the guttapercha and Apexit paste. Efficiency was evaluated clinically
      and radiographically three, six and twelve months later. RESULTS: Radiographic
      and clinical follow-up showed a significant radiographic improvement and absence
      of subjective symptoms in a very high percentage of the treated vital and avital
      teeth. The results of this study showed that in the observation period of 12
      months endodontic therapy was successful in 88.89% of vital teeth, and in the
      group of avital teeth the percentage was 91.67%. CONCLUSION: Endodontic treatment
      of the endoperiodontal lesions was sufficient and it was the basic condition to
      achieve a complete healing of endodontic-periodontal lesions. Such therapy
      ensures significant improvement or even complete healing of both types of
      lesions, of endodontic and periodontal origin.

PMID- 19764588
TI  - [The investigation of ultrasound efficacy in cleaning the surface of new
      endodontic instruments].
AB  - INTRODUCTION: Active parts and tips of various new stainless steel and nickel
      titanium endodontic instruments can be coated with fragments or metal residues,
      which can become detached during endodontic treatment. These fragments may
      obstruct the root canals or even reach the periapical tissue during biomechanical
      preparation and should be removed before clinical use. OBJECTIVE: The aim of this
      study was to evaluate the presence of metal residues on both new stainless steel
      and nickel-titanium endodontic instruments, and to determine the cleaning
      efficacy of ultrasound using distilled water or disinfectant solution for
      removing these residues. METHODS: Forty-eight stainless steel and nickel-titanium
      instruments were carefully removed from their original packages with dental
      tweezers, in order to avoid any contact with the cutting flutes and tips. The
      instruments were evaluated in term of metal debris presence, using scanning
      electron microscopy (SEM) and x-ray energy-dispersive spectroscopy (EDS). The
      instruments were then removed from the electron microscopy analysis stubs and
      placed in an ultrasonic bath for 15 minutes at a frequency of 28 kHz, using
      distilled water or disinfectant solution. The surfaces of the instruments were re
      evaluated after cleaning. RESULTS: Before ultrasound cleaning, a larger amount of
      metal debris was observed on the nickel-titanium endodontic instruments when
      compared to those made of stainless steel. The presence of metal particles on the
      instruments was evaluated by using EDS analysis. The use of ultrasound was
      effective in removing the metal residues from both types of endodontic instrument
      surfaces. CONCLUSION: The use of ultrasound proved to be an efficient method for
      the removal of metal particles from the surface of new stainless steel and nickel
      titanium endodontic instruments.

PMID- 19764589
TI  - [The influence of continuous magnetic field on periodontal tissues under
      overdentures].
AB  - INTRODUCTION: Last remained teeth with reduced alveolar support do not have long
      term prognosis, which is the reason for prolonging the life and thus providing a
      stable support of overdenture. The data from literature point out that static
      magnetic field has certain possibilities in resolving such problems. OBJECTIVE:
      Having in mind the pathogenetic factors which cause the reduction of the alveolar
      ridge and periodontal problems in our population, as well as osteoblastic and
      antiinflamatory activity, the aim of this investigation was to assess the effect
      of static magnetic field on periodontal tissue under the overdenture. METHODS:
      The investigation involved 38 partially edentulous patients, of both sexes and
      similar oral status who were bearers of a lower complete overdenture and upper
      classic complete denture as antagonist restoration. In the base of the lower
      overdenture the micromagnets were installed in the region of the remained teeth,
      which had static concentrated field of 60-80 mT power. The evaluation was done
      after 3, 6 and 12 months using the method of light densitometry. Periodontologic
      analysis was performed by standard and modified periodontologic tests. RESULTS:
      In patients with overdentures, after exposure to a magnetic field, the density of
      bone was not significantly changed, but the use of ANOVA disclosed changes in the
      observed interval. The tendency of increased density of the alveolar part of the
      observed region was noted. The region of the corresponding tooth of the
      contralateral side without magnetic influence showed decreased density of this
      region in the observed intervals. Plaque index and gingival index were improved
      underthe influence of the magnetic field, while after 6 and 12 months following
      the magnet insertion statistically significant changes were confirmed. The
      magnetic devices did not show any influence on the level of the gingival margin
      and junction epithelium. CONCLUSION: Static magnetic field is to be considered as
      a noninvasive procedure which is recommended to patients with reduced number of
      teeth and alveolar support.

PMID- 19764590
TI  - The significance of amlodipine on autonomic nervous system adjustment (ANSA
      method): a new approach in the treatment of hypertension.
AB  - INTRODUCTION: Cardiovascular autonomic modulation is altered in patients with
      essential hypertension. OBJECTIVE: To evaluate acute and long-term effects of
      amlodipine on cardiovascular autonomic function and haemodynamic status in
      patients with mild essential hypertension. METHODS: Ninety patients (43 male,
      mean age 52.12 +/- 10.7) years with mild hypertension were tested before, 30
      minutes after the first 5 mg oral dose of amlodipine and three weeks after
      monotherapy with amlodipine. A comprehensive study protocol was done including
      finger blood pressure variability (BPV) and heart rate variability (HRV) beat-to
      beat analysis with impedance cardiography, ECG with software short-term HRV and
      nonlinear analysis, 24-hour Holter ECG monitoring with QT and HRV analysis, 24
      hour blood pressure (BP) monitoring with systolic and diastolic BPV analysis,
      cardiovascular autonomic reflex tests, cold pressure test, mental stress test.
      The patients were also divided into sympathetic and parasympathetic groups,
      depending on predominance in short time spectral analysis of sympathovagal
      balance according to low frequency and high frequency values. RESULTS: We
      confirmed a significant systolic and diastolic BP reduction, and a reduction of
      pulse pressure during day, night and early morning hours. The reduction of
      supraventricular and ventricular ectopic beats during the night was also achieved
      with therapy, but without statistical significance. The increment of sympathetic
      activity in early phase of amlodipine therapy was without statistical
      significance and persistence of sympathetic predominance after a few weeks of
      therapy detected based on the results of short-term spectral HRV analysis. All
      time domain parameters of long-term HRV analysis were decreased and low frequency
      amongst spectral parameters. Amlodipne reduced baroreflex sensitivity after three
      weeks of therapy, but increased it immediately after the administration of the
      first dose. CONCLUSION: The results of the study showed that amlodipine affected
      autonomic modulation as a shift to sympathetic hyperactivity, but without
      statistical significance. In the selected group of patients with vagal
      predominance in sympathovagal balance, amlodipine increased sympathetic and
      decreases vagal activity. Therefore we conclude that amlodipine mostly exerts
      impact on autonomic function modulation in patients with vagal predominance in
      resting state.

PMID- 19764591
TI  - [Prognostic significance of cellular vascular endothelial growth factor (VEGF)
      expression in the course of chronic myeloid leukaemia].
AB  - INTRODUCTION: Increased angiogenesis in bone marrow is one of the characteristics
      of chronic myeloid leukaemia (CML), a clonal myeloproliferative disorder that
      expresses a chimeric bcr/abl protein. Vascular endothelial growth factor (VEGF)
      is one of the most potent and a specific regulator of angiogenesis which
      principally targets endothelial cells and regulates several of their functions,
      including mitogenesis, permeability and migration. The impact of elevated VEGF
      expression on the course of chronic myeloid leukaemia is unknown. OBJECTIVE: The
      aim of this study was the follow-up of VEGF expression during the course of CML.
      METHODS: We studied VEGF expression of 85 CML patients (median age 50 years,
      range 16-75 years). At the commencement of the study, 29 patients were in chronic
      phase (CP), 25 in an accelerated phase (AP), and 31 in the blast crisis (BC). The
      temporal expression (percentage positivity per 1000 analysed cells) VEGF proteins
      over the course of CML were studied using the immunohistochemical technique
      utilizing relevant monoclonal antibodies. It was correlated with the laboratory
      (Hb, WBC and platelet counts, and the percentage of blasts) and clinical
      parameters (organomegaly, duration of CP, AP, and BC) of disease progression.
      RESULTS: The expression ofVEGF protein was most pronounced in AP (ANOVA,
      p=0.033). The level of VEGF expression correlated inversely with the degree of
      splenomegaly (Pearson, r=-0.400, p=0.011). High expression of VEGF correlated
      with a shorter overall survival (log rank, p=0.042). CONCLUSION:
      Immunohistochemically confirmed significance of the expression of VEGF in
      dependence of the CML stage could be of clinical importance in deciding on the
      timing therapy. These data suggest that VEGF plays a role in the biology of CML
      and that VEGF inhibitors should be investigated in CML.

PMID- 19764592
TI  - [Immunoglobulin genes and T-cell receptors as molecular markers in children with
      acute lymphoblastic leukaemia].
AB  - INTRODUCTION: Acute lymphoblastic leukaemia (ALL) is a malignant clonal disease,
      one of the most common malignancies in childhood. Contemporary protocols ensure
      high remission rate and long term free survival. The ability of molecular genetic
      methods help to establish submicroscopic classification and minimal residual
      disease (MRD) follow up, in major percent responsible for relapse. OBJECTIVE: The
      aim of the study was to detect the frequency of IgH and TCR gene rearrangements
      and their correlation with clinical parameters. METHODS: Forty-one children with
      ALL were enrolled in the study group, with initial diagnosis of IgH and TCR gene
      rearrangements by polimerase chain reaction (PCR). MRD follow-up was performed in
      induction phase when morphological remission was expected, and after intensive
      chemiotherapy. RESULTS: In the study group IgH rearrangement was detected in
      82.9% of children at the diagnosis, while TCR rearrangement was seen in 56.1%. On
      induction day 33, clonal IgH rearrangements persisted in 39% and TCR
      rearrangements in 36.5% of children. CONCLUSION: Molecular analysis of genetic
      alterations and their correlation with standard prognostic parameters show the
      importance of risk stratification revision which leads to new therapy
      intensification approach. MRD stands out as a precise predictive factor for the
      relapse of disease.

PMID- 19764593
TI  - [Incidence of penile curvature in various forms of hypospadias].
AB  - INTRODUCTION: Hypospadias is a congenital anomaly of the penis, characterised by
      ectopically positioned urethral meatus and associated anomalies (cryptorchidism,
      inguinal hernia, penile curvature). Proximal forms of hypospadias, as severe
      cases, are particularly accompanied by penile curvature (chordee). Distal types
      are considered to be mild degrees. OBJECTIVE: To determine the incidence of
      congenital curvature within various forms of hypospadias in order to signify
      preoperative and intraoperative diagnosis of chordee as a part of hypospadias
      repair. METHODS: The total of 454 patients with hypospadias were treated
      surgically in a five-year period (2001-2006.) at the University Children's
      Hospital of Belgrade. The patients were divided into two groups according to the
      surgeon who had treated them. Only the first group of patients was tested for
      chordee as a part of standard procedure and complete treatment. In both groups we
      analyzed the number of patients treated for penile curvature within various types
      of hypospadias. We also compared scores in the two groups using Fisher test and
      chi2-test. RESULTS: Scanning retrospective, 104 cases (22.9%) of diagnosed and
      surgically corrected chordee were determined. In 31.6% of patients from the first
      group and 11.6% of patients from the second group we diagnosed and corrected some
      form of penile curvature was. Chordee was significantly more frequent in the
      first group, regarding hypospadias in general (p<0.01), as well as distal
      (p<0.05) and mid shaft forms (p<0.01). CONCLUSION: Penile curvature is not
      uncommon in hypospadias. In this study we report a significantly higher frequency
      as related to the patients in the second group who were not tested for curvature
      during hypospadias treatment. This is why standard techniques in hypospadias
      repair should definitely include the diagnosis and surgical correction of penile
      curvature.

PMID- 19764594
TI  - [Bone mineral density in patients with juvenile idiopathic arthritis].
AB  - INTRODUCTION: It is well known that juvenile idiopathic arthritis (JIA) as a
      chronic inflammatory disease with onset during the childhood, beside other
      complication, can lead to bone metabolism disturbance and osteoporosis.
      OBJECTIVE: To assess bone mineral density (BMD) in children with JIA and to
      identify factors playing role in bone mineral disturbance. METHODS: Seventy-five
      patients (26 male and 49 female) average disease duration 7.2 (2.4-16.8) years,
      and 73 age matched healthy control subjects (29 male and 44 female) participated
      in the study. Mean age of the groups was about 14.5 years. BMD was determined by
      dual x-ray absorptiometry (DEXA) of the lumbar spine (L2-L4). For further
      analysis we used the absolute value of BMD, expressed as g/cm2, Z score expressed
      as SD (relative value as standard deviation decline of normal BMD values of
      referent Italian population with identical age and gender), bone mineral content
      (BMC) as g/cm, and corrected BMD-BMDv as g/cm3. RESULTS: Z score in the group of
      patients was significantly lower (-1.02 +/- 1.6) in comparison to the control
      group (-0.09 +/- 1.4; p<0.001). BMD, BMDv and BMC were also statistically lower
      in patients with JIA. The lowest Z score was found in patients with systemic
      onset (-2.63 SD). Z score showed a statistically significant positive correlation
      with arthritis course (polyarticular course had lower Z score), body mass index
      and standard deviation score for height and weight. Statistically significant
      negative correlation was detected in regard to Z score and glucocorticoid (GC)
      treatment duration, GC cumulative dose, number of joints with limited range of
      motion, radiological stage and functional class. CONCLUSION: The results showed a
      decreased BMD in patients with JIA in comparison to the control group. Systemic
      onset, polyarthritis, longer treatment with GC and higher cumulative dosage, as
      well as higher damage level (functional status and radiological stage) are
      factors playing negative role in bone metabolism in children with JIA.

PMID- 19764595
TI  - Does the gestation age of newborn babies influence the ultrasonic assessment of
      hip condition?
AB  - INTRODUCTION: Ultrasound represents a method of examination of hips of newborn
      babies capable of defining hip condition and distinguishing stable and unstable
      hips based on morphological elements. It is accepted in a large number of
      countries as a method of examination of high risk newborns, or as a method of
      systematic screening. OBJECTIVE: The objective of this study was to investigate
      correlation between ultrasonically estimated hip maturity and respective
      gestation maturity both in premature and term-born babies, and to investigate the
      influence of different delivery types on hips condition. METHODS: In our study
      2045 patients, 1141 males and 904 females, were examined in at the Institute of
      Neonatology over a period of 5 years. The average age was 34.04 gestation weeks.
      There were significantly more premature (1698 or 83.03%) than term-born babies
      (347 or 16.97%). Ultrasound hip examination, as a screening method, was carried
      out according to Graf. It was followed by clinical examination. Results were
      analyzed by appropriate statistical methods (chi2-test, one-way ANOVA,
      multifactor ANOVA). RESULTS: The overall frequency of unstable hips was 3.2%,
      1.88% in males and 4.87% in females (p<0.05). 96.8% babies had stable hips, out
      of which 35.21% were mature and 61.59% immature. In the study of the breech
      presentation, out of 183 babies, unstable hips were found in 1.58% of male cases,
      and in 10.23% of female cases. CONCLUSION: Clinical screening of developmental
      dysplasia of the hip is insufficient for early diagnosis and decision about the
      treatment of premature babies. The high frequency of unstable hip type IIc
      (risky) and IId (decentralized) in premature babies requires early diagnosis and
      therapy. Wide swaddling for prematures should be applied up to eight months of
      age. Gentle manipulation is necessary while nursing and conducting physiotherapy
      of a premature baby.

PMID- 19764596
TI  - General characteristics of adolescent sexual behaviour: national survey.
AB  - INTRODUCTION: Investigation of adolescent sexual behaviour carried out on a large
      sample is primarily motivated by health and social problems which can occur when
      young people practice sex without protection and necessary information. There is
      no data that the national study on adolescent sexual behaviour has been conducted
      in the Serbian speaking area. OBJECTIVE: Monitoring and follow-up of trends in
      adolescent sexual behaviour. METHODS: The investigation sample comprised 1101
      adolescents (472 male and 629 female), aged 13-25 years. As an instrument of
      polling, the questionnaire "Sexual Behaviour" was used specifically designed for
      the purpose of this investigation. RESULTS: Eighty-four percent of males and 65%
      of females reported having sexual experience. The age of the first sexual
      experience, total number of partners, number of sexual partners in the last year
      and the last month were investigated, and the number of loved and sexual partner
      compared. In addition, the length of foreplay, frequency of sexual activity,
      masturbation, sexual dreams and sexual daydreams and engagement into alternative
      sexual activities (oral sex, anal sex, group sex, exchange of partners) were
      estimated, as well as the reasons for their practicing. Sexual desire and its
      correlation with personality dimensions, the frequency of sexual disorders
      (erectile and ejaculation problems, anorgasmia), abortion, rape and
      identification of the rapist, the use of condoms and other methods of
      contraception were assessed. CONCLUSION: It could be postulated that biological
      influence on sexual behaviour is powerful and resistant to the influence of time
      and place, as well as socio-cultural religious influences. A high rate of
      premarital sexual activity with a number of sexual partners, a relatively low
      rate of condom use and the fact that 4% of the female adolescents in this sample
      had an induced abortion suggest that there are gaps in the education provided to
      adolescents about sexual and reproductive risks within the Serbian speaking
      territory. An alarming statistic is that 5% of the female adolescents in this
      sample reported that they had been raped, or forced to participate in non
      consensual sex within an ongoing relationship with a regular partner. There is a
      need for systemic changes within the field of sexual education and protection
      from sexually risky behaviour among young adults.

PMID- 19764597
TI  - [Pacemaker optimization guided by echocardiography in cardiac resynchronization
      therapy].
AB  - INTRODUCTION: Cardiac resynchronization therapy (CRT) or biventricular pacing is
      a contemporary treatment in the management of advanced heart failure.
      Echocardiography plays an evolving and important role in patient selection for
      CRT, follow-up of acute and chronic CRT effects and optimization of device
      settings after biventricular pacemaker implantation. In this paper we illustrate
      usefulness of echocardiography for successful AV and VV timing optimization in
      patients with CRT. A review of up-to-date literature concerning rationale for AV
      and VV delay optimization, echocardiographic protocols and current
      recommendations for AV and VV optimization after CRT are also presented. OUTLINE
      OF CASES: The first case is of successful AV delay optimization guided by
      echocardiography in a patient with dilated cardiomyopathy treated with CRT is
      presented. Pulsed blood flow Doppler was used to detect mitral inflow while
      programming different duration of AV delay. The AV delay with optimal transmittal
      flow was established. The optimal mitral flow was the one with clearly defined E
      and A waves and maximal velocity time integral (VTI) of the mitral flow.
      Improvement in clinical status and reverse left ventricle remodelling with
      improvement of ejection fraction was registered in our patient after a month. The
      second case presents a patient with heart failure caused by dilated
      cardiomyopathy; six months after CRT implantation the patient was still NYHA
      class III and with a significantly depressed left ventricular ejection fraction.
      Optimization of VV interval guided by echocardiography was undertaken measuring
      VTI of the left ventricular outflow tract (LVOT) during programming of different
      VV intervals. The optimal VV interval was determined using a maximal LVOT VTI. A
      month after VV optimization our patient showed improvement in LV ejection
      fraction. CONCLUSION: Optimal management of patients treated with CRT integrate
      both clinical and echocardiographic follow-up with, if needed,
      echocardiographically guided optimization of AV and VV delays, which offers the
      possibility of additional clinical improvement in such patients.

PMID- 19764598
TI  - [Recurrent Fournier's gangrene in a diabetic patient].
AB  - INTRODUCTION: Fournier's gangrene (FG) is a fulminant form of infective
      necrotizing fascitis of the perineal, genital, or perianal regions caused by
      anorectal or urogenital and perineal trauma, more common in patients with
      diabetes mellitus and alcohol misuse. Despite contemporary management, mortality
      is still high and averages 20-30%. CASE OUTLINE: A 53-year-old extremely obese
      diabetic postmenopausal woman with the history of poorly regulated insulin
      dependent diabetes mellitus lasting for 20 years, and gangrene followed by
      autoamputation of minor labia a year ago, was admitted due to severe suprapubic
      pain and septic fever. Gynaecological examination revealed suprapubic abscess
      spontaneously perforated few hours prior to admission. Contraincision was
      performed and purulent green-yellowish discharge appeared. Microbial evaluation
      of the obtained specimen identified Peptostreptoccocus, Enterococcus and E.coli.
      Antibiotics were administered according to the sensitivity test and suprapubic
      tumour formation was irrigated and drained. The procedure lasted seven days and
      resulted in the healing of the pathological process. CONCLUSION: FG is still a
      life-threatening condition; so, diagnosis should be prompt with early surgical
      intervention, along with antibiotics and good supportive care. Proactive
      management of the diabetic patient with perineal infections is of extreme
      importance, in order to prevent the development of FG, the entity associated with
      very high mortality. According to the literature data available, this is the
      first reported case of FG relapse.

PMID- 19764599
TI  - [Mowat-Wilson syndrome--a case report].
AB  - INTRODUCTION: Mowat-Wilson syndrome (MWS) is characterised by severe mental
      retardation and multiple congenital anomalies. Key features for diagnosis are
      specific facial dysmorphism with uplifted ear lobes and Hirschsprung's disease.
      Ganglionic disorders of the colon, both the number of ganglion cells and the
      length of the aganglionic segment vary significantly in these patients. The
      disease is caused by ZFHX1B gene mutation. The management of MWS is symptomatic.
      CASE OUTLINE: We report a four-year-old boy with mental retardation, specific
      facial dysmorphy and multiple anomalies. During prenatal follow-up intrauterine
      growth retardation was revealed. Karyotype was normal. Clinical findings showed
      that growth and mental retardation, gastrointestinal disturbance and heart defect
      were predominant. A gastrostoma was inserted. Hypoganglionosis of the colon
      caused severe obstipation. He had a severe stenosis of the pulmonary artery and
      was a candidate for cardiac surgery. There were several attempts to establish
      diagnosis, but so far, without results CONCLUSION: Hirschsprung's
      disease/hypoganglionosis of the colon associated with other congenital anomalies
      or mental retardation require evaluation for dysmorphic syndromes. One of them is
      MWS, presented in this report.

PMID- 19764600
TI  - [Did we forget tetanus?].
AB  - INTRODUCTION: Currently, in our country (Republic of Serbia) tetanus is a rarely
      occurring disease, mainly affecting people older than 65 years of age. A small
      number of reported cases is mainly due to appropriate immunization. Therefore,
      each case of tetanus may be considered as failure of health care system to
      provide adequate immunization. CASE OUTLINE: A 71-year-old woman was injured in
      her garden. She sustained laceration in the left coccygeal region. The next day
      the wound was treated by a surgeon, but tetanus postexposure prophylaxis was not
      administrated. On the fifth day following the incident, the symptoms and signs of
      tetanus became apparent, and the patient died two days later. Postmortem
      examination revealed the wound that was not adequately treated, since there was a
      foreign body and a dressing inserted in the wound. Signs of acute (aerobic)
      infection were also present. CONCLUSION: Tetanus is a severe, potentially lethal
      disease that is absolutely preventable. Mistakes in immunization and surgical
      treatment of the wound can be considered as medical malpractice.

PMID- 19764601
TI  - [Mild cognitive impairment].
AB  - Mild cognitive impairment (MCI) is a syndrome that spans the area between normal
      ageing and dementia. It is classified into amnestic and non-amnestic types, both
      with two subtypes: single domain and multiple domains. Prevalence of MCI depends
      on criteria and population and can vary from 0.1 to 42% persons of older age. In
      contrast to dementia, cognitive deterioration is less severe and activities of
      daily living are preserved. Most impaired higher cognitive functions in MCI are
      memory, executive functions, language, visuospatial functions, attention etc.
      Also there are depression, apathy or psychomotor agitation, and signs of
      psychosis. Aetiology of MCI is multiple, mostly neurodegenerative, vascular,
      psychiatric, internistic, neurological, traumatic and iatrogenic. Persons with
      amnestic MCI are at a higher risk of converting to Alzheimer's disease, while
      those with a single non-memory domain are at risk of developing frontotemporal
      dementia. Some MCI patients also progress to other dementia types, vascular among
      others. In contrast, some patients have a stationary course, some improve, while
      others even normalize. Every suspicion of MCI warrants a detailed clinical
      exploration to discover underlying aetiology, laboratory analyses, neuroimaging
      methods and some cases require a detailed neuropsychological assessment. At the
      present time there is no efficacious therapy for cognitive decline in MCI or the
      one that could postpone conversion to dementia. The treatment of curable causes,
      application of preventive measures and risk factor control are reasonable
      measures in the absence of specific therapy.

PMID- 19764602
TI  - [Developmental hip dysplasia in adolescence].
AB  - The authors define adolescence and developmental dysplasia of the hip (DDH).
      Special attention is paid to pathological findings characteristic of DDH in
      adolescence (unrecognized and untreated DDH; treated DDH, but non-terminated
      treatment; DDH diagnosed with delay, inadequately treated, with complications).
      The authors emphasise that DDH treatment has to be successfully terminated well
      before the adolescence; possibilities are explained on management modes at the
      time of adolescence, and possible persons guilty for the persistence of later hip
      problems are indicated. Based on the authors' experience and having in mind all
      surgical possibilities for the treatment (pelvic osteotomies, femoral
      osteotomies, trochanteroplasties, leg length equalization procedures) the authors
      propose treatment protocols. The intention is to provide better treatment results
      and to prevent secondary hip arthrosis. Furthermore, how to improve the struggle
      against DDH is suggested.

PMID- 19764603
TI  - [Current clinical evidence on topiramate pharmacokinetics].
AB  - Topiramate is biochemically classified as a fructopyranose sulphamate. Discovered
      as early as 1979, during middle 1980's it was approved in many countries for the
      treatment of epilepsies and migraine prevention. More recently, in the
      experimental stage, possible new indications have been disclosed: treatment of
      obesity, bipolar disorder, also cessation of smoking, neuropathic pain, cerebral
      pseudotumour, bulimia, periventricular leucomalatia in preterm infants and
      alcohol addiction. Most epileptologists consider it to be the first choice
      antiepileptic drug in severe pharmacoresistant epilepsies. A substantial corpus
      of evidence in paediatric population has been accumulated that confirms its
      efficiency in the treatment of generalised tonic-clonic seizures, Lenox-Gestaut
      syndrome, partial, absence and combined seizures. Having a unique monosaccharide
      chemical structure among other anticonvulsant drugs, characterizes it with
      special pharmacokinetic features. This substance exhibits a low interindividual
      variability in plasma levels and hence it features predictable pharmacokinetics.
      A steady state plasma concentration of topiramate increases linearly with higher
      dosages. Serum protein binding is approximately 15%, and biologic half-life in
      healthy volunteers is considered to range from 20 to 30 hours. Mean expected
      distribution volume rates from 0.55-0.8 l/kg, and accordingly, the drug shows a
      low and saturable binding capacity toward erythrocytes. It has not been present
      at the market for a sufficiently long time that would enable us to speak about a
      significant accumulation of data on its metabolism based on post-registration 4th
      stage clinical trials. For this purpose, we have done a literature review in
      order to summarise so far reported experience on topiramate pharmacokinetics in
      patients and healthy adults. Deeper understanding of its pharmacokinetic profile
      could enable a better technological design of the produced drug and the choice of
      the adequate route of its administration, and accordingly a more rational
      treatment of severe epilepsies resistant to other drugs.

PMID- 19764604
TI  - [Martin Kirschner (1879-1942): the founder of modern trauma clinics and emergency
      medicine].
AB  - German surgeon Martin Kirschner (1879-1942) made a significant contribution not
      only to the general surgery but to orthopaedic surgery, traumatology and pain
      therapy as well. He gave a huge contribution to the institutions where he worked
      (Koningsberg), and some of them he had even built from the foundation (Tubingen,
      Heidelberg). He also established mobile hospitals and is the forefather of the
      trauma service and emergency medicine. In orthopaedics, he remains renowned for
      skeletal tractions, bone elongations, invention of thin wire, which is still
      widely used today in external fixation and which was named after him as Kirschner
      wire.

PMID- 19764605
TI  - Towards uniformity in English for medical purposes: evaluation and design.
AB  - INTRODUCTION: A thorough analysis of students' needs will enable teachers to
      build up a profile of a typical learner. OBJECTIVE: The objective of this study
      was to determine the current and target English language skill level and use the
      findings as guidelines in designing a uniform course. METHODS: The investigation
      was carried out at the Congress of Biomedical Science Students of Serbia held in
      Lepenski Vir in 2009. The investigation was conducted using a questionnaire and
      included 277 medical students of all study years and from all university centres
      of Serbia. RESULTS: The obtained results do not vary significantly among
      universities. The students marked writing and translation as their weakest skills
      and pointed out that their greatest problem areas were also vocabulary and
      grammar. On one hand, writing was ranked high among the skills which needed
      improvement but on the other hand, it was believed to be the least important in
      medical career. Speaking and listening were shown to be the most important for
      medical students. CONCLUSION: In designing the course, teachers need to be able
      to use approaches and methods flexibly and creatively in order to bring about
      positive results. Since course design is a dynamic process, teachers have the
      responsibility of negotiating a plan of work with the learners.

PMID- 19764606
TI  - [The protective action of cytokinins on the photosynthetic apparatus and
      productivity of plants under stress (review)].
AB  - A putative way of the protective action of cytokinins on the photosynthetic
      processes in crops experiencing various stress factors is considered. Various
      cytokinins are characterized. Pathways of the multiple effects of cytokinin
      preparations mediating the protection of the photosynthetic machinery from stress
      are described. Cytokinins interact with receptor proteins, and then the signal is
      transduced to primary cellular targets (primary response genes). These genes,
      which possess receptor domains, induce synthesis of the corresponding mRNAs and
      photosynthesis-related proteins of chlorophyll-protein complexes, the electron
      transport chain, and carbon metabolism, primarily, the key enzyme ribulose
      bisphosphate carboxylase/oxygenase. The protective action of cytokinins under
      stress conditions preserves the structure and function of the photosynthetic
      apparatus. The application of cytokinins to improving crop yields is discussed.

PMID- 19764607
TI  - [The purification and characterization of a novel lipid transfer protein from
      caryopsis of barnyard grass (Echinochloa crusgalli)].
AB  - A novel lipid transfer protein called Ec-LTP was isolated from resting caryopsis
      of weed barnyard grass Echinochloa crusgalli (L.) Beauv.; its molecular weight,
      amino acid content and N-terminal amino acid sequence were determined. Ec-LTP was
      a 9150 Da protein, containing eight cysteine residues, which formed four
      disulfide bonds. The isolated protein could significantly inhibit the development
      of pathogenic fungi Phytophthora infestans and Helminthosporium sativum, causing
      the late blight of potato and tomato and the root rot of herbs, respectively.

PMID- 19764608
TI  - [Ribonuclease from the hepatopancreas of the red king crab Paralithodes
      camtschatica].
AB  - Three enzyme preparations, two acid and one alkaline RNases, were isolated from
      the hepatopancreas of the red king crab Paralithodes camtschatica using DEAE
      cellulose chromatography and gel chromatography. The alkaline RNase was activated
      by Mg2+ ions and had a pH optimum of 7.2; the acid RNases, a pH optimum of 5.5.
      The molecular weight of the alkaline RNase was 19 kDa; two acid RNases, 33 and 70
      kDa, respectively. The enzymes exhibited a sufficiently high thermostability
      (IT50 = 53-55 degrees C) and were strongly inhibited by NaCl (IC50, 0.1-0.25 M).
      The alkaline RNase exhibited no specificity for heterocyclic bases, whereas the
      acid RNases hydrolyzed poly(U) and poly(A) at maximum rates.

PMID- 19764609
TI  - [The use of enzymatic preparation for the production of low molecular-weight
      chitosan from the king crab hepatopancrease].
AB  - This article describes the optimal conditions for the enzymatic hydrolysis of
      chitosan and its chemically-modified derivatives using the preparation extracted
      from the king crab hepatopancrease possessing pronounced hydrolythic activity.
      The following preparations were used: chitosan with a molecular weight of 100 kDa
      and an acetylation level of 0.15, carboxymethyl chitosan 200 kDa witih an extent
      of replacement of 0.23, and N-succinyl chitosan 390 kDa with an extent of
      replacement of 0.8. Low molecular-weight samples of chitosan and of its modified
      derivatives were obtained with the yields of 85, 55, and 80%, respectively. The
      conditions of the hydrolysis were as follows: an enzyme: substrate ratio of
      1:200, 37 degrees C, and 20 h duration of hydrolysis.

PMID- 19764610
TI  - [Macromolecular systems and bactericidal films based on chitin derivatives and
      silver nanoparticles].
AB  - A new polymer composite based on carboxymethylchitin and silver nanoparticles was
      obtained in order to produce biodegradable wound coating films. The number of
      metal nanoparticles in the composite may be easily regulated as was verified by
      UV-VIS-spectroscopy data. A comparative evaluation of silver nanoparticle size in
      the initial system and in the polymer composition was performed by means of
      photon correlation spectroscopy. Composite films revealed a pronounced
      concentration-dependent antibacterial activity towards strains Salmonella
      typhimurium and Staphilococcus aureus.

PMID- 19764611
TI  - [Microbial polymers as a degradable carrier for pesticide delivery].
AB  - The possibility of use of polyhydroxyalkanoates (PHAs), biodegradable microbial
      polyesters, as a carrier for pesticides (alpha-hexachlorocyclohexane and lindane)
      for targeted and controlled delivery of these compounds to soil was investigated.
      The kinetics of polymer degradation and the dynamics of pesticide release from
      the extended-release formulations was studied. It is shown that pesticides
      embedded in a degradable polymer (PHA) carrier are released gradually and slowly,
      without surges, as the polymer is degraded by the soil microflora. The microbial
      soil component actively responded to the addition of the polymer as an additional
      nutrient substrate: the latter was degraded and then utilized. The rate of the
      pesticide release to the soil can be regulated by varying the polymer-pesticide
      ratio.

PMID- 19764612
TI  - [Catalytical properties of Arthrobacter nicotianae cells, a producer of glucose
      isomerase, immobilized in xerogel of silicium dioxide].
AB  - Arthrobacter nicotinanae cells, producers of glucose isomerase, were immobilized
      in xerogel of silicium dioxide, and properties of the resulted heterogeneous
      biocatalysts were investigated in the process of isomerization of monosaccharide
      (glucose and fructose). The glucose isomerase activity of the resulted
      biocatalysts was shown to be 10 U/g, on average, taking into account the loss of
      the activity upon the immobilization, which amounted to 50% of the cell activity
      in suspension. The rate of the fructose isomerization increased linearly in the
      range of 55-80 degrees C with the temperature coefficient 1.3. The biocatalysts
      were stable in this range; they were rapidly inactivated, however, at increasing
      temperature. The half-inactivation time was six to seven h and five min or less
      at 80 degrees C and 85 degrees C, respectively. The half-inactivation time of
      heterogeneous biocatalysts was 50-90 h in the periodic process of isomerization
      of 2 M monosaccharides at 60 degrees C in the presence of the immobilized
      Arthrobacter nicotinanae cells.

PMID- 19764613
TI  - [The introduction of the 9alpha-hydroxy group into androst-4-en-3,17-dione using
      a new actinobacterium strain].
AB  - A 9alpha-hydrolase activity of a new actinobacterium strain identified as
      Rhodococcus erythropolis based on the analysis of a 16S rRNA gene sequence (1417
      nucleotides) towards androst-4-en-3,17-dione (AD) was studied. In the presence of
      glucose in the medium, this strain completely transformed AD (4-20 g/l) into
      9alpha-hydroxy-AD over 20-48 h. This culture was able to grow and perform AD
      9alphahydroxylation at a concentration of dimethyl formamide up to 9%.
      Crystalline 9alpha-hydroxy-AD was isolated with a yield of over 90%.

PMID- 19764614
TI  - [Periodic bioleaching of refractory gold-bearing pyrite ore].
AB  - The main characteristics of a periodic bioleaching of the refractory gold-bearing
      pyrite ore from the Tandzut deposit (Armenia) with the help of moderate
      thermophilic bacterium Sulfobacillus thermosulfidooxi-dans subsp. asporogenes and
      original thermotolerant strains Leptospirillum spp. were studied. The optimal pH
      for oxidizing the ore by S. thermosulfidooxidans subsp. asporogenes was 1.8; the
      pulp density providing maximal iron leaching rate was 10%. The intensity of
      oxidation processes decreased at higher ore concentrations. When using S.
      thermosulfidooxidans subsp. asporogenes, the largest amount of iron passed into
      the solution at the initial oxidant (Fe3+) concentration of 1.3 g/l.
      Cocultivation of S. thermosulfidooxidans subsp. asporogenes and Leptospirillum
      spp. increased the degree of pyrite ore leaching to 98.4% vs. 34.1% in the case
      of the former bacterium alone.

PMID- 19764615
TI  - [Oxidation of sulfur-containing substrates by an association of acidophilic
      chemolithotrophic microorganisms].
AB  - Quantitative and qualitative changes in the content of elements in the solid and
      liquid phases occurred as the pulp moved through fermenters during biooxidation
      of an ore flotation concentrate. The association of microorganisms were adapted
      for utilizing sulfur-containing substrates; however, the rate of their oxidation
      was insufficient, which led to an increase in the amount of sodium cyanide
      required for gold recovery. The replacement of one-fourth of the liquid phase of
      the pulp (density, 13%) with a mineral medium without an energy source, the
      fractional addition of FeSO4 x 7H2O (1 g/l per day), and the improvement of pulp
      aeration made it possible to increase the content of SO4(2-) by 80.7, 86.2, and
      58.5%, respectively. When one-fourth of the liquid phasa of the pulp (density,
      24%) was replaced with a mineral medium without an energy source, the rate of
      additional oxidation of sulfide minerals increased, which increased the
      efficiency of gold extraction into solution and gold recovery on charcoal by 3.4
      and 3.6%, respectively, and reduced sodium cyanide consumption by 3 kg/ton.

PMID- 19764616
TI  - Lactobacilli and dairy propionibacterium with potential as biopreservatives
      against food fungi and yeast contamination.
AB  - Naturally fermented and raw foods contain a range of organisms that may have
      benefit as additives in some foods and food processing. In particular, potential
      anti-fungal properties of these organisms may be potentially utilised as natural
      alternatives to chemical additives used to delay and prevent spoilage by fungi
      and yeast. This study examined 12 novel bacteria previously isolated from food as
      possible biopreservatives. The bacteria from the lactobacilli and dairy
      propionibacterium groups were tested by agar overlay method for their ability to
      inhibit the growth of 10 fungi and one yeast commonly associated with food
      contamination. Eight among eleven tested lactic acid bacteria demonstrated broad
      spectrum of antifungal activity. Strong fungi inhibition was also demonstrated by
      the dairy propionibacterium, but efficacy was growth medium dependant. Only one
      fungi, Geotrichum candidum was highly resistant to the bacteria. Variation
      between the inhibition results for different bacteria identifies the importance
      of careful strain selection, and the benefits of strain combinations when
      selecting biopreservatives for foods.

PMID- 19764617
TI  - [Antifungal and phytostimulating characteristics of Bacillus subtilis Ch-13
      rhizospheric strain, producer of bioprepations].
AB  - Bacillus subtilis Ch-13 industrial strain was shown to have a wide spectrum of
      antagonistic activities against different species of phytopathogenic fungi and
      bacteria. The B. subtilis Ch-13 strain produces lytic enzymes; cyanide and other
      antifungal metabolites; stimulates plant growth, producing phytohormones-auxin
      derivatives. This strain by 2.5 times reduced the quantity of tomato plants
      infected with phytopathogenic fungus Fusarium oxysporum during inoculation. Fungi
      abundance on roots with bacterial inoculation was 6.9 times less than in the
      absence of inoculation. The application of detected antifungal metabolites as
      biochemical markers for the strain enables to control the stability of
      physiologic and biochemical characteristics of the producer, and ensures a rapid
      quality assay of biopreparations with high performance liquid chromatography
      (HPLC).

PMID- 19764618
TI  - [The effects of ultraviolet irradiation upon structure and antioxidant activity
      of silenan from bladder campion callus].
AB  - Effects of UV-B (280-315 nm) and UV-C (254 nm) at various doses upon callus of
      bladder campion (Silene vulgaris (M.) G. were studied. It was revealed that UV
      irradiation results in the decrease in arabinose and galactose residues in the
      silenan--the pectin fraction isolated from callus. The silenan possesses
      antioxidant activity (AOA) as assessed by the reaction with a stable radical. At
      the irradiation of callus by UV, the AOA of the silenan and the relative content
      of phenolic compounds in it increased; the highest increase was observed after
      the irradiation of callus by UV-B. Positive correlation between the AOA of the
      pectin fraction and an increase in phenolic compounds was revealed. This
      evidences that the AOA of the silenan relates to and is partially determined by
      phenolic compounds in its composition. The UV irradiation may be used as a tool
      to modify the structural features of the cell walls' polysaccharides in order to
      produce physiologically-active polysaccharides with desired properties.

PMID- 19764619
TI  - [The inhibition of potato tubers wound reparation].
AB  - The multiple washing of the wound surface of potato tubers by water adversely
      affected the protective properties of wound periderm. Immune inhibitor beta-1,3
      beta-1,6 glucan had a property of local effect and inhibited the process of wound
      healing. The pentasaccharide of xyloglucan caused necrosis of potato tuber tissue
      and prevented the wound reparation process.

PMID- 19764620
TI  - [Hydrogen peroxide production in wheat leaves infected with the fungus Septoria
      nodorum Berk. strains with different virulence].
AB  - The effect of two strains of the phytopathogenic fungus Septoria nodorum Berk. of
      different virulence on the intensity of local generation of hydrogen peroxide in
      common wheat leaves and the role of oxidoreductases in this process was studied.
      Differences in the pattern of hydrogen peroxide production in wheat plants
      infected with high- and low-virulence pathogen strains have been found. The low
      virulent S. nodorum strain caused a long-term hydrogen peroxide (H2O2) generation
      in the infection zone, whereas the inoculation of leaves with the highly virulent
      strain resulted in a transient short-term increase in the H2O2 concentration at
      the initial moment of contact between the plant and the fungus. It was shown that
      the low level of H2O2 prOduction by plant cells at the initial stages of
      pathogenesis facilitates S. nodorum growth and development. The decrease in the
      H2O2 concentration induced by the highly virulent S. nodorum strain is determined
      by inhibition of the oxalate oxidase activity in plant tissues and by the ability
      of the fungus to actively synthesize an extracellular catalase. The pattern of
      hydrogen peroxide generation at the initial stages of septoriosis may serve as an
      index of virulence of S. nodorum population.

PMID- 19764621
TI  - [Design of experimental approaches on the base of standard proteins for testing
      blood biopreparations and immunoperoxidase conjugates specific to human and
      animal immunoglobulines G].
AB  - Using standard forms of immunoglobulin (Ig) G and albumin, we have studied
      electrophoretic and chromatographic profiles of samples of pharmaceutical blood
      biopreparation batches. The usability of standard proteins was also demonstrated
      by testing analytical characteristics of immunoperoxidase conjugates specific to
      human and animal IgG (anti-IgG IPC). In particular, we suggest an additional
      estimation of analytical characteristics of anti-IgG IPC by the enzyme reaction
      kinetics with the standard dilution which is calculated by the direct enzyme
      liked immunoassay on the homologous IgG-antigen.

PMID- 19764622
TI  - Estimation of methods of protein delivery into mammalian cells--a comparative
      study by electroporation and bioporter assay.
AB  - To test the efficiency of some alternative methods for protein delivery into live
      cells were used rEGFP (recombinant Enhanced Green Fluorescent Protein) and HeLa
      cells as model system. The compared methods, electroporation (up to 10%) and
      Bioporter (up to 20%), deliver proteins and peptides to the cells with
      efficiency, enough for functional studies of mammalian cells. Thus, the delivery
      by either of both methods, followed by fluorescence activated cell sorting (FACS)
      of the cell population, can give a sufficient number of uniformly loaded cells
      for different studies including transcription assays and gene therapy.

PMID- 19764623
TI  - [Evaluation of the activity of hydrolases and their inhibitors using substrates
      immobilized on agarose gel].
AB  - A simple and convenient method for the quantitative evaluation of the activity of
      hydrolytic enzymes and their inhibitors has been proposed. This method is based
      on the immobilization of a substrate on agarose gel and the following evaluation
      of the enzyme activity by measuring the hydrolysis area around the well
      containing the enzyme solution. The method was shown to be applied to the
      evaluation of the activity of proteinases and amylases and the inhibitors of
      these enzymes in different biological objects.

PMID- 19764624
TI  - [Gibberellin A3 detection in plants with high-performance liquid chromatography].
AB  - A new method of gibberellin A3 detection based on high-performance liquid
      chromatography has been elaborated. It combines high accuracy and low cost, and
      includes the following stages: fixation with liquid nitrogen; extraction of
      alcohol-soluble substances; purification with freezing, reextraction in ethyl
      acetate, and thin-layer chromatography; and detection with HPLC. Chromatographic
      conditions and methods of substance identification have been determined. The
      method allows the use of modest amounts of plant material (5-20 g), at which
      variability does not exceed 7%, and the total loss of substance is approximately
      3%. The results of gibberellin A3 detection in buckwheat are presented.

PMID- 19764625
TI  - [Detection of polymeric forms of dihydroquercetin by optical absorption and light
      scattering].
AB  - Two methods for the detection of long polymers in dihydroquercetin (DHQ)
      preparations has been developed. The first method is based on UV
      spectrophotometry. It was shown that the quantity of long polymers in aqueous
      solutions can be estimated by the ratio of the absorption bands at 328 and 290
      nm, since the 328-nm band was attributed to the monomeric form of DHQ, whereas
      the 290-nm band was attributed to both the monomeric and polymeric forms. The
      second method is based on the high-sensitive measurement of light-scattering
      intensity in aqueous solutions of diluted DHQ preparations using a
      spectrofluorometer with crossed monochromators. It has been shown that the
      filtration of DHQ solutions through Millipore filters with a pore diameter of
      0.05-0.45 microns makes it possible to nearly completely eliminate long polymers
      and their aggregates. Long polymers at high concentrations can aggregate. The
      longest polymers and their aggregates may be 0.1 mm in length, which leads to
      fluctuations in the light-scattering intensity on the second and minute time
      scale.

PMID- 19764626
TI  - [The Report on Scientific and Scientific-Organizational Activity of Section of
      Physiology of Branch of Biological Sciences RAS in 2008].

PMID- 19764627
TI  - [Electroencephalogram alpha activity: modern interpretations].
AB  - This review of modem interpretations of nature and physiological significance of
      EEG alpha activity was inspired with the following aims: 1--alpha activity
      phenomena determination, 2--summering the experimental and theoretical data about
      the nature, origin and neurophysiological mechanisms of the alpha oscillations
      distribution, 3--description of the most famous brain alpha activity structure
      hypothesis, 4--presentation of authors hypothesis about EEG alpha activity
      indices as: 1--individual alpha peak frequency in parietal-occipital brain area,
      2--alpha spindle features: length, amplitude variability and steepness, 3-
      reactivity to visual stimulations as: amount and time duration of amplitude
      suppression and frequency range width in which amplitude suppression is appeared.

PMID- 19764628
TI  - [Modern problems of energetics of internal organs].
AB  - The review considers the general mechanisms of energy exchange in an organism,
      which determine its volume. The data are given on the energy exchange in various
      internal organs (heart, lungs, kidneys, liver, gastrointestinal tract). The
      reasons for a high energy exchange in the internal organs are considered and also
      for their substantial role in participating in the total energy budget of an
      organism.

PMID- 19764629
TI  - [Temperature and cardiotropic effects of kyotorphin and neokyotorphin in
      hibernating and nonhibernating animals].
AB  - Physiological effects of kiotorphyn (KT) and neokiotorphyn (NKT) has been
      reviewed. These peptides were isolated from the brain of hibernating ground
      squirrel Citellus undulates (CU) and assumed to be endogenous regulators of
      hibernation NKT does not alter the process of entering to hibernation, but
      induces arousal from the sleeping. KT administration in squirrel delays the rise
      of heart rate and body temperature associeated with awakening provoked in the
      middle but not at the final stage of hibernation bout. Neither KT nor NKT induce
      physiological effects in rats and mice under normal environmental conditions. In
      mice with induced hypothermia (17-18 degrees C) NKT accelerates restoration of
      body temperature, whereas KT induces progressive hypothermia. In addition, NKT
      modulates cardiotropic effects of nucleotides found in physiologically active
      fractions of hibernating squirrel tissues. NKT as well as KT modify sensitivity
      of cardiovascular system to adrenaline and AMP in rats one day after hypothermia.

PMID- 19764630
TI  - [Bioethics and biomedical experiment evolution from Alkmaion to Pavlov. Dedicated
      to 160 years since I.P. Pavlov's birthday].
AB  - Ethic aspects of biomedical experiment evolution from Alkmaion to Pavlov, are
      analysed. The history of reflexes in the paradigm of mechanitsism and
      antropomorphism is reinterpreted. It is emphasized that animal life and their
      behaviour exceed the bounds of mechanitsizm. It is grounded the necessity of
      humane treating living organisms. The theory of conditioned reflexes and the
      method of physiological synthesis are considered in the context of bioethics. It
      is shown that Pavlov's methodological approaches are in correspondence with the
      modern principles of bioethics of scientific animal experiments.

PMID- 19764631
TI  - [Polycationic peptides as nonhormonal regulators of chemosignal systems].
AB  - This review summarizes and analyzes both literature data and results of our own
      studies on molecular mechanisms of action of natural and artificially created
      polycationic peptides on functional activity of heterotrimeric G-proteins and G
      protein-coupled signal systems. There are considered peptide toxins from insect
      venom, synthetic peptides that are derivatives of cytoplasmic loops of receptors
      of the serpentine type as well as artificially created peptides with linear,
      branched, and dendrimere structures. Action of most of these peptides on activity
      of G-proteins is highly selective and those themselves are able to mimic the
      hormone-activated receptor to be thereby non-hormonal regulators of the signal
      systems coupled with heterotrimeric G-proteins.

PMID- 19764632
TI  - [Significance of electron interactions of fatty acids of phospholipid molecules
      in the organism adaptation to habitation temperature].
AB  - Data in the fatty acid composition of muscle tissue phospholipids of some
      representatives of gastropod molluscs (Gastropoda) have been presented for the
      first time. In the lake phytophagues Lymnaea stagnalis and Lymnaea ovata the long
      chained C22-acid was not detected, whereas in the predator common whelk Buccinum
      undatum, C22:6omega3 was present. Comparison of absorption spectra (240-720 nm)
      of lipid extracts of the studied invertebrates and of rat has been performed. The
      obtained data are discussed from the point of view of participation of pi
      electrons of phospholipid fatty acid molecules in adaptation of membranes to the
      habitation temperature, which arises owing to interelectron attraction and to the
      process of formation of Cooper's pairs.

PMID- 19764633
TI  - [Comparative-enzymologic study of phosphatase activity of hydrobionts from
      Pacific Ocean].
AB  - Activities of acid phosphatase are studied with use as substrates of phenyl
      phosphate, alpha- and beta-glycerophosphates in various organs and tissues of a
      large group of industrial hydrobionts of the Pacific basin (12 fish species, 7
      invertebrate species. and one mammalian species) and of alkaline phosphatase in
      various organs of the Commander (Berryteuthis magister) and the New Zealand
      (Nototodarus sloani sloani) squids. Intertissue and interspecies differences have
      been revealed in the substrate and inhibitory specificity of the studied enzyme
      preparations. The method of isolation and a partial purification of preparations
      of acid phosphatase from tissue of gonads and of alkaline phosphatase from
      tissues of kidney and liver of individuals of industrial squid species is
      described.

PMID- 19764634
TI  - [Catalytical properties of the liver monoamine oxidases of the commander squid
      Berryteuthis magister from various habitation zones].
AB  - A detailed kinetic analysis is performed of enzymatic reactions of deamination of
      tyramine, tryptamine, serotonin, benzylamine, beta-phenylethylamine, and
      histamine under action of liver monoamine oxidase (MAO) of the Commander squid
      Berryteuthis magister from various habitation zones in the Bering and Japan Seas.
      There has been revealed a substrate inhibition by high concentrations of all
      studied substrates, which seems to indicate mutual effect of various MAO forms
      present in liver of the studied squids. Analysis of kinetic parameters of
      enzymatic reactions of deamination of six studied substrates and the substrate
      inhibitory analysis with use of two derivatives of acridine and deprenyl indicate
      the enzyme heterogeneity, the presence of at least two MAO forms and the absence
      of intraspecies differences in MAO of the Commander squids from various
      habitation zones. The most active was the MAO form responsible for serotonin
      deamination. There were obtained quantitative difference in substrate specificity
      and reaction ability with respect to inhibitor of proflavin for the liver MAO of
      the Commander and Pacific squids.

PMID- 19764635
TI  - [Effects of several exorphins and endorphins on the escape reaction of the
      cockroach Periplaneta americana under elevated temperature conditions].
AB  - The ability of several alimentary opioid peptides (exorphin C, rubiscolin-5,
      cytochrophi-4) and endorphins (met-enkephalin, dynotphin A(1-10), beta
      neoendorphin) to change the escape reaction of the cockroaches Periplaneta
      americana at their placement into a hot chamber was studied. The ED50 values
      increasing twice the insect stay time in the hot chamber as well as duration and
      dynamics of the effects were determined. It has been shown that ED5 decreases
      statistically significantly with increase of the length of the peptide molecule
      and its affinity of duration of the effects and to an increase of their affinity
      to delta-receptors - to prolongation of the reaction (more than150 min). In the
      group of alimentary peptides (exorphins) the most active was a fragment of D
      ribulose-1,5-biphosphate carboxylase/oxigenase rubiscolin-5 (ED5 = 386 nM per
      individual). This might indicate a specific ability of some plant proteins to
      regulate (decrease) the insect protective behavior.

PMID- 19764636
TI  - [Neurohumoral mechanisms of the rat heart adaptation to overload].
AB  - The present study confirms involvement of the sympathicoadrenal system in
      adaptation of heart to overload. Besides, at formation of chronic heart failure
      (CHF) there have been revealed a rise of the histamine and serotonin levels in
      blood plasma and myocardium as well as glucocorticoid hyperactivation.

PMID- 19764637
TI  - [Th role of inhibitory interneurons in mechanisms of regulation of sensory
      synapses formed by thalamic and cortical inputs in pyramidal cells of the
      dorsolateral amygdala nucleus].
AB  - The work deals with study of role of inhibitory interneurons in the process of
      regulation of sensory currents converging on soma of pyramidal cells of the
      dorsolateral amygdala nucleus as well as of role of these interneurons in
      mechanism of regulation of plasticity of amygdalar synapses. It has been shown
      that the part of the spontaneous inhibitory postsynaptic currents recorded on the
      dorsolateral amygdale pyramidal cells is relatively high and amounts to about a
      half of the total amount of the recorded events. Analysis of the evoked
      postsynaptic responses has shown the interneurons to regulate activity and
      duration of these responses due to the postsynaptic membrane hyperpolarization as
      a result of activation of GABA(A)-receptors. Also studied was role of
      interneurons in providing mechanisms of the long-term potentiation of the
      synaptic responses evoked by stimulation of cortical and thalamic inputs. Block
      of effect of interneurons with help of picrotoxin has been shown to lead to an
      increase of evoked potentiation of synaptic responses.

PMID- 19764638
TI  - [Dissolution of the wakefulness-sleep cycle in patients with catatonic form of
      schizophrenia].
AB  - Polysomnograms of two patients with catatonic form of schizophrenia of different
      duration of the disease were recorded and analyzed. Pronounced disorders of the
      wakefulness-sleep cycle (WSC) were revealed. Apart from differences connected
      with duration of the disease and treatment with corresponding medications, there
      were detected the general features indicating dissolution of the central nervous
      system and the very wakefulness-sleep cycle. A certain similarity of the found
      WSC disturbances with the earlier shown WSC disturbances in rats with
      predisposition to catalepsy was noted. The conclusion is made about domination of
      diencephalic influences over the telencephalic one in the studied patients.

PMID- 19764639
TI  - [External proprioceptors of locust locomotor organs and their changes during
      early larval ontogenesis].
AB  - This work studies topography and structure of such important insect external
      proprioceptors as campaniform sensillae (CS). These mechanoreceptors are
      essential components of insect posture and locomotion regulation and participate
      in control of various forms of insect motor behavior (walking, jump, flight).
      There are traced their quantitative changes as well as differences in
      distribution of groups of these leg receptors at consecutive stages (from the 1st
      to the 4th) of ontogenetic development of larva of the locust Locusta migratoria
      L. The presence of groups of CS in proximal parts of extremities has been noted
      as early as in the 1st instar larvae. The CS groups in the wing pads were
      revealed only in the 4th instar larvae. The presented data allow connecting
      changes in structure and distribution of these proprioceptors on central
      generators of the locomotion rhythms.

PMID- 19764640
TI  - [Peculiarities of valve movement and cardiac activity of the bivalvian mollusc
      Mytilus galloprovincialis during various stress conditions].

PMID- 19764641
TI  - [Comparative analysis of heart activity of the crayfish (Pontastacus
      leptodactylus) by methods of plethysmography and electrocardiography].

PMID- 19764642
TI  - [Some connections of the optic lobes with the supraesophageal ganglion of the
      dragonfly Aeschna grandis].

PMID- 19764643
TI  - [Wave changes [Ca2+]i in rat skeletal myocytes in hyperpotassium solution].

PMID- 19764644
TI  - [Multifunctionality and homeostasis. Regularities of the organism functioning
      important for maintenace of homeostasis].
AB  - This paper is a continuation of our first paper ""Zonal model" of description of
      homeostasis" [1] that discussed some general regularities of the organism
      functioning connected directly with maintenance of homeostasis. It might seem
      that consideration of such general issues could have been only of theoretical
      interest; however, for the recent years, a trend has been formed in direction of
      cholistic physiology and medicine when there are considered first of all the
      organism functioning regularities responding for maintenance of its integrity in
      norm and in pathology. A particular attention in the present paper is paid to
      consideration of multifunctional possibilities of organs and functional blocks.
      In our opinion, such analysis can promote solution of general problems of
      physiology and medicine and provides a possibility to better understand
      organization of processes in the organism throughout the lifespan as well can
      help in elucidation of causes of some chronic diseases.

PMID- 19764645
TI  - [Copy number variation is a new form of genomic diversity].
AB  - This is a short review of recently described copy number variation of some
      segments of DNA. The origin of this phenomenon, the localization of these
      segments and their possible role in regulation of gene expression are discussed.
      The copy number variation should be regarded as a new form of genomic diversity.

PMID- 19764646
TI  - [Novel human embryonic stem cell lines C612 and C910].
AB  - Novel human embryonal stem cell lines C612 and C910 have been established from
      hatching blastocytes. Cells were cultivated in mTeST medium on mouse fibroblast
      feeder-layers. They express common pluripotent markers such as alkaline
      phosphatase, Oct 3/4, SEEA-4, Nanog, Rex1. Immunophenotyping of these cells by
      flow cytometry revealed expression of CD90 (Thy-1) and CD117 (c-kit) antigens and
      weak or no expression of CD13, CD34, CD45, CD130, HLA class I and HLA class II
      antigens. This pattern of surface antigen expression is common for human
      embryonic stem cells. G-banding assay of C612 and C910 metaphase plates showed
      that karyotypic structure of these cells was normal both in chromosome number and
      structure. The cells are pluripotent because of their capability to generate
      embryoid bodies, undergo spontaneous differentiation and express markers of all
      germ layers: nestin, keratin, vimentin (ectoderm), alpha-fetoprotein (entoderm),
      and muscle alpha-actinin (mesoderm). Thus, C612 and C910 cells have all
      attributes of typical human embryonic stem cells (diploid, capable of self
      renewal, express pluripotent markers and differentiate into three germ layers)
      and may be of potential use for fundamental and regenerative medicine researches.

PMID- 19764647
TI  - [Realization pathways of prolactin modulating influence on the cAMP-dependent
      mechanism of meiosis regulation in bovine oocytes].
AB  - Cyclic AMP is one of the key regulators of mammalian meiosis. In the present
      work, realization pathways of the previously revealed modulating influence of
      prolactin (PRL) on the cAMP-dependent mechanisms of meiosis regulation in bovine
      oocytes were studied. A comparative investigation of individual and combined
      effects of PRL (50 ng/ml) and an activator of adenylate cyclase forskolin (FK. 20
      microM) on the meiotic reinitiation and nuclear maturation completion in cumulus
      enclosed and cumulus-free oocytes was performed. It has been shown that the
      pattern of PRL influence on the meiotic resumption in oocytes devoid of cumulus
      cells depends on the presence of FK in the culture medium. Furthermore,
      realization of this influence is not associated with the activation of
      cytoplasmic isoforms of protein kinase C. It has been also found that PRL
      inhibits the retarding action of FK on the completion of oocyte nuclear
      maturation in both the presence and absence of cumulus cells. The findings
      suggest that PRL may modulate the functioning of the cAMP-dependent mechanism of
      meiosis regulation by the direct action on bovine oocytes, with realization of
      the action being independent of the metabolic coupling of oocytes with cumulus
      cells.

PMID- 19764648
TI  - [The characters and specific features of new human embryonic stem cells lines].
AB  - Four continuous human embryonic stem cell lines (SC1, SC2, SC3 and SC4), derived
      from the blastocysts has been described. The cell lines were cultivated on
      mitotically inactivated human feeder cells. The cell lines SC1 and SC2 have
      passed through 150 population doublings and the cell lines SC3 and SC4 -- near
      120 populations doublings, which exceeds Hayflick limit sufficiently. These cell
      lines maintain high activity of alkaline phosphatase, expression of transcription
      factor OCT-4 and cell surface antigens (SSEA-4, TRA-1-60 and TRA-1-81),
      confirming their ESC status and human specificity. Immunofluorescent detection of
      antigens, characteristic of ectoderm, endoderm and mesoderm confirms the ability
      of these cells to retain their pluripotency under in vitro condition. PCR
      analysis revealed expression of six genes specific for pluripotent cells (OCT-4,
      NANOG, DPPA3/STELLA, TDGF/CRIPTO and LEFTYA). Correlation between the level of
      proliferative activity and the character of DNA-bound fluorescent staining was
      found. Fluorescent dyes, Hoechst 33342 and PI, produced diffuse staining of the
      nuclei in slowly proliferating cells of the SC1 and SC2 lines. In contrast, in
      actively proliferating cells of the SC3 and SC4 lines, the clear staining of the
      nuclei was observed. Upon changing the cultivation condition, proliferative
      activity of SC3 and SC4 lines decreased and became similar to that of SC1 and SC2
      lines. The character of the fluorescent staining of all these lines was also
      shown to be similar. These results show that quality of the fluorescent staining
      with Hoechst 33342 and PI reflects the level of proliferation. Possible causes
      and mechanisms of this feature of human ESC are discussed.

PMID- 19764649
TI  - [Telomeric DNA allocation in chromosomes of common shrew Sorex araneus,
      Eulipotyphla].
AB  - Recently we have displayed shrew species, Iberian shrew S. granarius, with
      telomeres of unusual for mammals structure, including long telomeres on the short
      acrocentrics arms containing 213 kb on average and short telomeres (3.8 kb) on
      the other chromosomal ends (Zhdanova et al., 2005, 2007). However, it is not
      clear if such telomeres are characteristic of all shrew species or only of S.
      granarius. S. granarius and common shrew Sorex araneus are the sibling species.
      In this investigation by using modified Q-FISH, we demonstrated that telomeres in
      S. araneus from different chromosomal races differing in the numbers of
      metacentrics contain 6.8-15.2 kb of telomeric tracts. Thus, the S. araneus
      telomere lengths appeared to correspond with telomere lengths both in shrews and
      majority wild mammalian species, and S. granarius has telomeres with unique or
      scarce structure. Furthermore, using DNA and RNA modified with probe high
      specificity to telomeric repeats (PNA and LNA) we showed that interstitial
      telomeric sites in S. araneus chromosomes contained mainly telomeric DNA and
      their localization coincided with some evolutionary breakpoints. Interstitial
      telomeric DNA in S. granarius chromosomes was not revealed. Thus, distribution of
      telomeric DNA can greatly differ even in closely related species whose
      chromosomes are composed from almost identical chromosomal arms.

PMID- 19764650
TI  - [Spontaneous aneuploidy level in blood cells of fertile females].
AB  - In this study we present the results of molecular-cytogenetic investigation of
      blood cells of fertile women of reproductive age. We used cultivated and
      uncultivated cells and two sets of FISH probes with direct and indirect labeling.
      The mean aneuploidy levels of 4 chromosomes were determined and statistical
      limits were scored. Aneuploidy levels determined in cultivated lymphocytes by
      multicolor FISH varied from 0.1 to 1.3%. The mean aneuploidy level for all
      chromosomes (13, 18, 21 and X) was 1.39%. The limit mutation detection was 3.4%.
      We found differences in results obtained with the use of direct and indirect
      labeling. It was shown that cultivating process influenced the aneuploidy level.
      Absolute error of FISH technique was 0.13%, relative error - 4.08%.

PMID- 19764651
TI  - [Chromosomal polymorphism and cytotypes Endochironomus tendens F. (Diptera,
      Chironomidae) from reservoirs in the Saratov and Samara Regions].
AB  - Chromosomal polymorphism of phytophilous chironomidae, Endochironomus tendens F.,
      from reservoirs in the Saratov and Samara Regions has been studied. Cytophotomaps
      of polytene chromosomes of the species have been worked out in details, and the
      found chromosomal sequences cadastre has been established. E. tendens F.
      cytotypes (karyomorphs I and II) have been analyzed.

PMID- 19764652
TI  - [Influence of exogenous cytokinins on dynamics of development and differentiation
      of infection structure of the causal organism of wheat powdery mildew].
AB  - Using methods of light and electron scanning microscopy, development and
      infection structures differentiation of the causal organism of wheat powdery
      mildew, Erysiphe graminis DC. f. sp. tritici March., was investigated under
      influence of exogenous zeatin. It has been shown for the first time that
      physiologically active materials, in particular, cytokinin type phytohormons
      affect on the dimensions of halo revealed at the site of pathogen penetration by
      cytochemical staining. Treatment with zeatin influenced conidia germination and
      pathogen growth at the ectophytic stage. Dose response dependence of zeatin for
      number of mature colonies of pathogen (6 days after an infection) has been
      presented by multiphase curve with two maxima (1 and 3 microM) and minimum (1.5
      microM). Similar curves have been received for the number of normal appressoria
      and the diameters of the large halo that possibly shows the existence of factors
      affecting both parameters, and the final number of pathogen colonies, as well.
      The obtained data demonstrate that multiphase dose response curve for development
      of the causal organism of powdery mildew under effect of cytokinins is originated
      from the factors acting at early stages of pathogenesis.

PMID- 19764653
TI  - [Nitroxidergic neurons in some nuclei of medulla oblongata in human and rat].
AB  - Seven nuclei of medulla oblongata bearing a relation to human and rat bulbar
      vasomotor center and in which four types of neurons were distinguished by
      intensity of reaction to NADPH-diaphorase were analyzed. The analysis has shown
      that majority of human and rat nuclei have similar pattern on nitroxid-positive
      neuron distribution: neurons with high NO-synthase activity predominate in
      vasomotor nuclei, and neurons with low one predominate in sensitive nuclei.

PMID- 19764654
TI  - [Ubiquitination of EGF receptors with C-terminal domain deletion and point
      mutations during endocytosis].
AB  - Analysis of ubiquitination of EGF receptor carrying different mutations of C
      terminal domain was done. The mutants differed both by the set of major
      autophosphorylation sites that determine the way of interaction with ubiquitin
      ligase c-Cbl, and by the presence of lysine residues which can be possible
      acceptor sites for ubiquitin. It was found that the receptor lacking tyrosine
      kinase activity due to lysine for phenylalanine substitution at ATP-binding site
      of tyrosine kinase (TK) domain (K721) failed to be ubiquitinated as well as the
      receptor without all binding sites for c-Cbl (CD165), while dynamics and pattern
      of ubiquitination of other deletion mutants was significantly different. The
      mutant lacking Grb2 binding sites but able to bind c-Cbl directly (CD123) was
      minimally ubiquitinated and only at early stages upon EGF endocytosis
      stimulation. At the same time, the receptor possessing all binding sites for Cbl
      but lacking C-terminal domain of 63 aminoacid residues (CD63) which contains two
      autophosphorylation sites (Y1148 and 1173) and 4 lysines, was less ubiquitinated
      and had more low-ubiquitinated forms comparing to the WT one. However, these
      lysines are not acceptor sites for ubiquitin since the full-size receptor lacking
      like CD63 the same major autophosphorylation sites underwent ubiquitination
      similar to the deletion mutant. Thus, C-terminal region of the EGF receptor,
      being not a substrate for ubiquitination per se, is involved in its regulation.
      It was also found that ubiquitination pattern at fast endocytosis differed from
      those at slow one. In the first case the total level of EGFR decreased
      dramatically as a result of efficient lysosomal degradation. The level of
      receptor-associated c-Cbl was practically the same, while the total intracellular
      c-Cbl dropped. Treatment of cells with proteasomal inhibition MG132 blocked the
      loss of Cbl only partially. In the second case, total amount of both EGF receptor
      and c-Cbl did not notably change that suggested recycling pathway for receptors
      even despite them beeng ubiquitinated.

PMID- 19764655
TI  - Are the symptoms of diabetic peripheral neuropathy in Nigerian patients
      objective? An evaluation using the United Kingdom Screening Test (UKST) and Bio
      Thesiometry.
AB  - BACKGROUND: Symptoms suggestive of peripheral neuropathy (PN) in diabetes
      mellitus (DM) do not always indicate presence ofunderlying PN. OBJECTIVE: A
      pioneering study among Nigerian diabetic subjects to evaluate the objectivity of
      their symptoms of PN using two objective diagnostic instruments for PN the United
      Kingdom Screening Test (UKST) and Bio-Thesiometry. SUBJECTS AND METHODS: One
      hundred and twenty diabetic participants and a similar number of non-diabetic
      controls were screened for symptoms of PN using the UKST symptoms score and
      subsequently separated into two groups those with symptoms ofPN and those
      without. The "symptomatic" cases and controls were further evaluated with the
      UKST signs score and Bio-Thesiometry to assess the objectivity of the symptoms.
      RESULTS: Among 120 diabetic participants, 83(69.2%) had neuropathic symptoms (the
      symptomatic cases) while 10 (8.3%) of the 120 non-diabetic controls had
      neuropathic symptoms (the symptomatic controls). Among the cases, UKST signs
      score detected PN in 89.2% (74/83) and Bio-Thesiometry 71.1% (59/83), the
      difference in the ability of the two methods to detect PN in this group being
      statistically significant (X2 = 8.51, df = 1, p < 0.01). Among the controls, UKST
      detected PN in 100.0% (10/10) compared to Bio-thesiometry (50.0%; 5/10), the
      difference in the ability of the two methods to detect PN in this group also
      being statistically significant (X2 = 4.27, df = 1, p < 0.05, using continuity
      correction factor). The difference in the ability of both methods to detect PN
      between the cases and controls was however not statistically significant (X2 =
      0.68, df = 1, p > 0.3) CONCLUSION: The symptoms of PN among Nigerian diabetic
      subjects when evaluated with a gold standard for scoring the symptoms (the UKST
      symptoms score) are real, objective and truly indicate presence of underlying PN.
      Diabetic subjects presenting to medical clinics with symptoms of PN should
      receive serious attention and evaluation using this gold standard to detect early
      those with genuine PN and are at risk of foot ulceration from PN.

PMID- 19764656
TI  - Prevalence of human immunodeficiency virus in ophthalmic surgical patients.
AB  - AIM: The aim of this study was to determine the incidence of human
      immunodeficiency virus in one hundred and sixteen (116) ophthalmic patients who
      had surgery over a two year period (July 2003 to June 2005) in the Department
      ofOphthalmology of the University ofBenin Teaching Hospital, Benin City.
      MATERIALS AND METHODS: A two year prospective study was carried out on 116
      ophthalmic patients who had surgery between July 2003 and June 2005, A total of
      116 patients were screened for HIV 1 & 2. An informed consent was obtained from
      all the patients. Patients who did not give their consent were excluded from the
      study. RESULTS: The total number of patients screened was one hundred and sixteen
      (116).There were 61 males and 55 females The age range was lyear to 78years with
      a mean age of 46 +/- 22.2 years (SD). The highest number of patients, 25 was
      found in the age group 61-70 years, comprising 21.6 of the total number of
      patients, followed by 24 patients in the 51 60 years age group. Three (3)
      patients comprising 2.6% were HIV positive. There were 2 females aged 25 and 50
      years and a male aged 42years. The 25 year old female presented with squamous
      cell carcinoma of the conjunctiva, while the 57 year old woman had
      panophthalmitis. The male patient had herpes zoster ophthalmicus. He developed
      corneal opacities as complications of herpes zoster and had a peripheral
      iridectomy done to improve his vision. CONCLUSION: Although the HIV
      seropositivity rate of 2.6% is low, there is a need to do routine testing for HIV
      seropositivity in ophthalmic surgical patients who are billed for surgery as it
      gives them an opportunity to know their HIV status, thus enabling them to take
      appropriate preventive or treatment measures where necessary. HIV screening
      should be mandatory for high risk patients such as those with panophthalmitis,
      herpes zoster and squamous cell carcinoma of the conjunctiva that are markers for
      HIV.

PMID- 19764657
TI  - Urinary tract infection in febrile children in Maiduguri north eastern Nigeria.
AB  - One hundred and forty five children aged 1 month to sixty months who had fever at
      presentation to the paediatric department of University of Maiduguri Teaching
      Hospital were investigated for urinary tract infection in this prospective study
      from November 2004 to October 2005. Prevalence of urinary tract infection was
      found to be 13.7 per cent. While the female sex and malnutrition were found to be
      significantly associated with urinary tract infection, height of temperature and
      symptoms referable to urinary system were not. Ninety per cent of the isolates
      were Gram negative; mainly coliform Spp, the remaining 10 per cent were due to
      staphylococcus aureus. Gentamicin was still found to be effective against most of
      the urinary pathogens. However, clavulinic acid potentiated amoxicillin,
      ampicillin, nalidixic acid and cotrimoxazole were found to be poorly effective.
      We therefore conclude that all ill children especially younger ones presenting
      with fever be screened for urinary tract infection. A regular surveillance of
      urinary tract infection pathogens and their antibiotic sensitivity pattern is
      recommended.

PMID- 19764658
TI  - Stress and psychological health of medical students in a Nigerian university.
AB  - OBJECTIVE: Physician job satisfaction is one indicator of the overall health of
      our health care delivery system. Excellent but dissatisfied physicians could
      decide to leave the practice of medicine or highly talented students could opt
      for different careers if the perception that medicine is not a fulfilling career
      exists. This study aims to investigate the level of course satisfaction, its
      relationship to psychological disorder and presence/absence of stress among
      medical students. Physician job satisfaction is one indicator of the overall
      health of our health care delivery system. Excellent but dissatisfied physicians
      could decide to leave the practice of medicine or highly talented students could
      opt for different careers if the perception that medicine is not a fulfilling
      career exists. This study aims to investigate the level of course satisfaction,
      its relationship to psychological disorder and presence/absence of stress among
      medical students. MATERIALS AND METHODS: A cross-sectional study was conducted
      among 410 medical students of the University of Benin, Nigeria. The respondents
      completed a self-administered questionnaire and a standard instrument The General
      Health Questionnaire (GHQ 28). RESULTS: The response rate was 93.9%. Two hundred
      and forty four (63.4%) of respondents were satisfied with their course, 331
      (86.0%) of them felt medicine was stressful. There was also a statistical
      significant difference in the level of stress among the various levels of medical
      students. One hundred and twenty three (31.9%) medical students indicated that
      they would not study medicine again if given a second chance. One hundred and
      twelve (29.1%) medical students had psychological disorder. More dissatisfied
      students had psychological disorder than satisfied students and this difference
      was found to be statistically significant. CONCLUSION: The level of perceived
      stress among medical students was found to be high and a significant number of
      students had psychological morbidity. There is a need to identify and correct the
      causes of dissatisfaction among these groups of students in order to improve on
      the psychological state of the students. Stress management training is also
      required as majority of the medical students found the course stressful.

PMID- 19764659
TI  - Millennium Development Goals: an assessment of awareness and perceptions of
      attainability by health workers in Owo, Nigeria.
AB  - AIM: To assess the awareness of the United Nations Millenium Development Goals
      (MDGs) by some Nigerian health workers and also their perceptions of the
      attainability of the goals. SUBJECT AND METHODS: Through the means of a
      structured questionnaire served on 92 consenting health workers selected by
      stratified sampling technique ,information regarding their bio data, awareness of
      the millennium development goals (MDGs), the duration and source of the awareness
      and their perception of attainability of the goals were obtained. The feasibility
      of attainment of the goals was rated as: very attainable, attainable, and not
      attainable. RESULTS: All the respondents were by then aware of the MDGs. Most of
      the respondents (57.6%) became aware within the preceding year, i.e., 2006; while
      only very few (2.2%) had been aware 6-7 years earlier (2000 and 2001). Some
      respondents (46.7%) got to know of MDGs through their colleagues while others
      (32.6%) got to know through the print and electronic media. The remaining others
      (20.7%) were informed through the sensitization efforts of the government and non
      government agencies. The highest degree of optimism for the attainment ofMDGs
      were displayed largely for health related MDGs; i.e., the goals 4, 5 and 6.
      CONCLUSIONS & RECOMMENDATIONS: Majority of the respondents were aware of MDGs.
      Most adjudged the attainment of MDGs feasible. The government and other stake
      holders should sensitize the populace, strengthen the health system and ensure
      equitable access to health care.

PMID- 19764660
TI  - An audit of deaths in the emergency room in the University College Hospital
      Ibadan.
AB  - INTRODUCTION: Death rates in the accident and emergency department may be a
      reflection of the quality of care in the hospital. Trauma related mortality is a
      significant cause of preventable death. METHOD: A retrospective study was
      conducted in the accident and emergency department of the University College
      Hospital Ibadan (Nigeria) using the hospital records to determine the pattern of
      mortality over one year. RESULT: Five thousand one hundred patients attended the
      accident and emergency department in the year reviewed. One hundred and sixty
      eight (3.3%) mortalities were recorded .There were 97 males and 71 females with
      mean ages of 49+/-37.8 and 42+/-30.7 years respectively. 46% of the patients had
      medical (non-trauma non-surgical) related diagnoses. Trauma constituted 31% of
      the mortalities with an average probability of survival of 80% at presentation.
      Head injury and multiple long bone fracture were the commonest causes of trauma
      related mortalities. CONCLUSION: Trauma is a preventable cause of death. The poor
      outcome of the trauma patients underscores the need to equip the attending
      doctors in the emergency room with basic skills in trauma care.

PMID- 19764661
TI  - Prevalence of HIV seropositivity in patients with lymphoid malignancies in a
      tertiary centre in southern Nigeria.
AB  - OBJECTIVE: The human immunodeficiency virus (HIV) epidemic has a significant
      impact worldwide and infected subjects are at increased risk of developing
      cancer. We aim to determine the HIV seropositivity of lymphoid malignant patients
      in a tertiary centre in Southern Nigeria. METHOD: The course of disease in 275
      patients with lymphoid malignant disorders at the University of Benin Teaching
      Hospital, Benin City, Nigeria, was analysed from 1996 to 2006. Blood specimens
      screened for antibody to HIV infection were confirmed by Western blot and the
      CD4+ lymphocyte count was measured by flow cytometry technique. RESULTS: A total
      of 275 patients aged 18-72 years were studied. Of the 275 lymphoid malignancies
      11 cases were found to be HIV seropositive giving a seroprevalence of 4%. The
      most frequent lymphoid malignancy in association with HIV seropositivity was non
      hodgkin's lymphoma (NHL) with a prevalence of 4.12% over the less frequent
      lymphoid neoplasms. The overall median CD4+ lymphocyte count was 185 microl with
      9 cases seropositive for HIV below 200 microl (P<0.0001). CONCLUSION: We conclude
      that the seroprevalence of HIV infection in patients with lymphoid malignancies
      was 4% with NHL being the most common neoplasm associated with HIV infection in
      concordance with studies in the Diaspora.

PMID- 19764662
TI  - Day case adenoidectomy: is it safe?
AB  - OBJECTIVE: To document the Clinical outcome of Day Case Adenoidectomy in Children
      in a Nigerian tertiary health Institution and a private Ear, Nose and Throat
      Consultant Cinic. METHODOLOGY: This is a prospective study of twenty eight
      children without any co-morbid condition operated for adenoidectomy between June
      2002 and May 2004. The patients were admitted on the day of surgery and
      discharged within 12 hours post surgery. RESULT: A total number of 28 patients
      were operated for adenoidectomy. 16 children were treated as planned day cases
      and 12 were treated as inpatients. 50% of the patients were in the age group of 2
      4 years. There were 12 males and 4 females with a M:F ratio of 3: 1. All the
      parents of the patients had access to cars and 75% resided within 30 minutes of
      travelling time from the hospital. CONCLUSION: Day case adenoidectomy is
      relatively safe and may prove advantageous considering long surgical waiting
      lists, preventing Hospital acquired infection and minimizing cost of
      hospitalization.

PMID- 19764663
TI  - Audit of gynaecological laparoscopies in National Hospital Abuja, Nigeria.
AB  - CONTEXT: The scope oflaparoscopy is increasing in contemporary gynaecological
      practice. There is scanty data on gynaecological laparoscopy in Nigeria.
      OBJECTIVE: To determine the rate, indications, perioperative characteristics and
      complications of gynaecological laparoscopy at National Hospital, Abuja. STUDY
      DESIGN, SETTING AND SUBJECTS: A retrospective review of gynaecological
      laparoscopies performed at the National Hospital, Abuja, Nigeria over a four year
      period (2001-2004). RESULTS: There were 58 gynaecological laparoscopies during
      the study period, and a rate of 28.7 laparoscopies per 1000 gynaecological
      operations. The incidence is low due to occasional logistic problems with the
      equipment and multiple strike actions by health workers. The procedure was done
      wholly for diagnostic purposes, the major indication being infertility in 88.9%
      of the patients. Majority (54.9%) of the patients had the procedure performed
      during the luteal phase of their menstrual cycle, as opposed to the proliferative
      phase. The procedure was performed by consultants or senior residents in 50 (98%)
      of the patients. All the patients had general anaesthesia for the laparoscopies.
      There was no major complication or operative mortality in the patients whose case
      folders were analysed. CONCLUSION: The gynaecological laparoscopy rate is low, at
      28.7 per 1000 gynaecological operations; it was done mainly for elective and
      diagnostic purposes, the major indication being infertility and it was generally
      safe with absence of major perioperative or postoperative complications.

PMID- 19764664
TI  - Case fatality among hypertension-related admissions in Enugu, Nigeria.
AB  - OBJECTIVE: To determine the case fatality rate and ultimate causes of death among
      patients with hypertension-related conditions admitted to an urban tertiary
      hospital, METHOD: A five-year review of hypertension-related admissions into the
      medical wards of the University of Nigeria Teaching Hospital, Enugu, between 1995
      and 1999, was undertaken. RESULTS: 7220 patients were admitted into the medical
      wards during the period under review. Of these, 445 (6.2%) were due to
      hypertension-related causes. Of the later, 285 (64%) were males while 160 (36%)
      were females. One hundred and ninety one of the hypertension-related admissions
      died, giving a case fatality of 42.9%. The mean age at death was 54.8+/-15.8
      years (53.5+/-15.9 years for males; 57.2+/-15.4 years for females, t=2.47,
      df=189, p=0.117). Sixty six percent of these were males while thirty four percent
      were females. Eighty six (45%) of the deaths occurred during acute hypertensive
      crises such as cerebrovascular accidents, hypertensive encephalopathy, and acute
      renal failure. Other important complications leading to death were congestive
      cardiac failure, accounting for thirty three cases (17.3%); and chronic renal
      failure 32 (16.8%). In twenty one (11%) hypertension-related admissions, the
      causes of death were not documented. CONCLUSION: Hypertension, with its related
      complications, constitute a major cause of morbidity and mortality in our medical
      wards. The case fatality rate is very high and often mostly avoidable
      complications were responsible. There is need to further study the determinants
      of these avoidable causes of death.

PMID- 19764665
TI  - Relations of the neck of groin hernias to pubic tubercle.
AB  - OBJECTIVE: The traditional anatomical and surgical teaching is that any hernia
      with the neck above and medial to the pubic tubercle are inguinal. Present day
      surgical authors and teachers mostly adhere to this teaching but observe a
      difference in this relationship in clinical demonstrations. This confuses most
      medical students and surgical residents. This all-important clinical teaching
      should hence be revisited. Hence this study was to ascertain and validate
      clinically the true relationship of pubic tubercle and the neck of groins hernia.
      METHOD:  DESIGN: Aprospective observational study. SETTING: Surgical Outpatient
      Clinic of Wesley Guild Hospital, Ilesa Unit of the Obafemi Awolowo University
      Teaching Hospital Complex, Nigeria. SUBJECTS AND MEASUREMENTS: Consecutive
      patients seen in the clinic with uncomplicated groin hernias were studied from
      January 1993 to December 2004. Examinations were done to ascertain the
      relationship of the groin hernias to the pubic tubercle. RESULTS: 96.8% of
      inguinal hernias have their necks above and lateral to pubic tubercle while all
      femoral hernia had their necks below and lateral to the pubic tubercle.
      CONCLUSION: Location above or below the pubic tubercle should be used as the sole
      difference between femoral and inguinal hernias in clinical demonstrations. More
      observations and inguinal dissections will be necessary for further
      clarification.

PMID- 19764666
TI  - Single versus two layer suturing for wound closure after inguinal hernia repair.
AB  - OBJECTIVE: Method of skin-subcutaneous closure after inguinal herniorrhaphy
      affects the operation time and immediate outcome of the wound. The study was
      aimed to assess the effects of a single layer closure of the skin and
      subcutaneous wound of inguinal herniorrhaphy, in contrast to the conventional two
      layer closure. METHOD:  DESIGN: Prospective randomized controlled trials.
      SETTING: Obafemi Awolowo University Teaching Hospital Ile-Ife, Osun State,
      Nigeria. PATIENTS AND METHOD: All adult patients attending surgical out patient
      clinic with uncomplicated inguinal hernia and had surgery, after randomization
      into two groups from June 2000 Dec 2005 were included in the study. One group had
      one layer - closure i.e. closure of skin and subcutaneous tissues together at
      once while the second group had two layer closure i.e. closure of skin and
      subcutaneous tissues separately. Duration of operation and complications were
      documented for comparison. RESULTS: One hundred and eighty wounds were studied in
      160 patients; the extra wounds being from bilateral inguinal hernias. There were
      93 wounds in group one (two layer closure) and 87 wounds in group two (one layer
      closure. There was no significant difference between healing of wounds and
      appearance of scars in both groups. The single layer closure group was, however,
      apparently quicker. (P= 0.006). CONCLUSION: The immediate outcome of the wound in
      both groups was similar. The medical personnel time was saved by closing the
      wound in single layer.

PMID- 19764667
TI  - Audit of the red cell units supply of a busy hospital blood bank in Nigeria.
AB  - BACKGROUND/OBJECTIVE: Blood bank audit embraces all procedures from blood
      procurement to the long -term consequences of transfusion which helps to identify
      opportunities for improvement. We have therefore looked at red cell transfusion
      in our hospital to identify areas that will require improvement. METHOD: Data was
      collected retrospectively from the hard copy record of the blood bank for a
      period of one month. RESULTS: Request was made for 1210 red cell units;
      crossmatch was made for 64% of the request. All units crossmatched were issued,
      of these 4.15% were returned unutilized. 5.1% were issued as uncrossmatched. The
      Obstetrics/Gynaecology unit recorded the highest blood usage and the medical unit
      the least. The use of blood by the emergency and paediatric were the same. The
      crossmatch:transfusion ratio for the hospital was 0.9:1. This study has shown
      that the crossmatch and transfusion rates are almost equal and only a small
      percentage was returned unused. CONCLUSION: This showed that there is inadequate
      supply of blood. There is a need to assess the reason for transfusion and
      establishing a blood transfusion advisory committee by the hospital. This will
      ensure interaction and collaboration between blood suppliers and users to improve
      the quality of transfusion practice. The new policy establishing a national
      transfusion service will also improve the transfusion service but emphasis has to
      be put on donor recruitment and donor care.

PMID- 19764668
TI  - Primary bone tumours in a tertiary hospital in Nigeria: 25 year review.
AB  - BACKGROUND: Primary bone tumors remain a daunting challenge to orthopaedic
      surgeons. The challenge is heightened in developing countries due to limited
      diagnostic and therapeutic facilities and ignorance. The published literature on
      the subject is sparse in our environment. OBJECTIVE: To describe the pattern of
      primary bone tumors seen in a tertiary hospital in Nigeria. METHODS: This is a
      retrospective review of all the histologically confirmed primary bone tumours
      seen at Lagos University Teaching Hospital (LUTH) over a 25 year period. RESULTS:
      A total of 242 patients (aged 7.5 to 62 years) with a mean of 25.3 years were
      studied. One hundred and forty four patients (59.5%) were males and 98 (40.5%)
      were females. The peak age incidence was in the age group 11-20 years. One
      hundred and thirty (53.7%) of the tumors were benign. Among these Osteochondroma
      was the commonest accounting for 36 cases (27.7%) followed by Osteoclastoma, 28
      cases (21.5%). Osteosarcoma accounted for 66 cases (58.9%) of all primary
      malignant tumours in the study. CONCLUSION: This study showed that primary bone
      tumours were mainly benign, occurred predominantly in the second decade of life
      with a male preponderance. Osteochondroma and Osteosarcoma were the most common
      benign and primary malignant bone tumours respectively.

PMID- 19764669
TI  - Lipid profile in pre-dialysis chronic kidney disease patients attending
      University of Maiduguri Teaching Hospital, Maiduguri-Nigeria.
AB  - BACKGROUND/OBJECTIVES: Cardiovascular disease is a major cause of morbidity and
      mortality among patients with chronic kidney disease, and accounts for 50% of all
      deaths in them. Dyslipidaemia does not only accelerate atherosclerosis in these
      patients but also progresses the renal disease. This study therefore set to
      investigate the pattern of lipid profile in pre-dialysis chronic kidney disease
      patients. METHODS: This was case control study of 63 pre-dialysis chronic kidney
      disease patients attending University of Maiduguri teaching Hospital and 60
      control subjects. All factors that may lead to dyslipidaemia were excluded in all
      subjects except hypertension. Lipid profiles were measured by standard methods.
      Data were analyzed using a statistical software SPSS version 11.0. Their observed
      differences in mean-SEM values were analyzed for statistical significance using
      Student's t-test andp-value <0.05 was considered significant. RESULTS: the
      mean+SEM of total cholesterol 4.50+0.14 mmol/L and triglycerides 2.18+0.10 mmol/L
      in patients were significantly higher than that of the controls 3.79+0.11 mmol/L
      and 1.19+0.06 mmol/L respectively, p<0.05. Similarly the mean+SEM of LDL
      2.62+0.16 mmol/L and LDL/HDL ratio 3.53+0.12 in patients were significantly
      higher when compared to that of the controls 2.04+0.16 mmol/L and 2.04+0.08
      respectively, p<0.05. However, although the mean+SEM HDL in patient 1.07+0.07
      mmol/L, was lower than that of the controls 1.21+0.06 mmol/L, the difference was
      not statistically significant, p>0.05. The pattern of lipid profile did not
      change with severity of disease and dyslipidaemia in patients were more in
      triglycerides, 68.3% and HDL, 63.5% than in TC, 22.2% and LDL, 17.5%. CONCLUSION:
      Dyslipidaemia is common in pre-dialysis chronic kidney disease patients. It is
      pertinent to investigate and treat dyslipidaemia early in the course of the
      disease as it may prevent further progression of the renal damage.

PMID- 19764670
TI  - Obstetric outcome in pregnant women subjected to domestic violence.
AB  - OBJECTIVE: To determine the prevalence of domestic violence and its relationship
      to adverse obstetric outcomes amongst pregnant women who deliver at a tertiary
      level hospital in Zaria, Nigeria. METHOD: A cross-sectional study involving 310
      women who delivered at the labour ward. Questionnaires were administered to
      parturient women. Details of their socio-demographic characteristics and
      obstetric outcome were compiled and the relationship to experiences of domestic
      violence studied. RESULTS: The prevalence of domestic violence was 28.4%. There
      was positive relationship between domestic violence during pregnancy, non
      supervision of pregnancy and poor attendances to antenatal clinic (p<0.05). There
      was however, no statistically significant relationship between domestic violence,
      and complications of labour and neonatal outcome (p>0.05). CONCLUSION: The
      prevalence of domestic violence in pregnancy is high in this environment. Poor
      attendances to the antenatal clinic is a significant association.

PMID- 19764671
TI  - Prevalence of malaria parasitaemia and malaria related anaemia among pregnant
      women in Abakaliki, South East Nigeria.
AB  - BACKGROUND: Malaria currently is regarded as the most common and potentially the
      most serious infection occurring in pregnancy in many sub Saharan African
      countries. This study was undertaken to evaluate the prevalence of malaria
      parasitaemia and malaria related anaemia among pregnant women in Abakaliki, South
      East, Nigeria. MATERIALS AND METHODS: This is a cross sectional, descriptive
      study conducted in two tertiary health institutions in Abakaliki, South East,
      Nigeria (Ebonyi State University Teaching Hospital And Federal Medical Centre).
      Using systematic sampling method, 193 pregnant women were selected from the
      health institutions for the study. Their blood were analysed for haemoglobin
      status and malaria parasite. Data were also collected using an interviewer
      administered questionnaire. All the data were analysed using Epi info version 6
      statistical software. RESULTS: Response rate was 100%. Twenty nine percent
      prevalence of malaria parasitaemia was detected, more common among primigravidae.
      Women with higher parity had higher frequency of anaemia in pregnancy. More than
      half of the pregnant women (51%) were in their second trimester at the time of
      booking. There was no case of severe anaemia requiring blood transfusion.
      CONCLUSION: Our pregnant women register late for antenatal care. Prevalence of
      malaria parasitaemia is high in our environment as well as anaemia in pregnancy,
      using the standard WHO definition. It is suggested that effort should be
      intensified to make our women register early for antenatal care in order to
      identify complications early. Intermittent preventive treatment for malaria
      should be incorporated into routine drugs for antenatal women.

PMID- 19764672
TI  - Perception of neonatal jaundice among women attending children out patient and
      immunization clinics of the UPTH Port Harcourt.
AB  - BACKGROUND: Neonatal Jaundice (NNJ) is a common disorder worldwide. Early
      identification and proper management is needed to prevent the serious
      neurological complications associated with it. OBJECTIVE: To determine the
      knowledge of the women attending Children Outpatient (CHOP) and Immunization
      clinics on the causes, treatment and complications of neonatal jaundice. METHOD:
      Women who brought their children/wards to the immunization/children out patient
      clinics at the University of Port Harcourt Teaching Hospital Port Harcourt were
      interviewed using structured questionaire. RESULTS: There were 255 mothers who
      participated in the study. Of these 30 (11.8%) have never heard of neonatal
      jaundice while 225 (88.2%) have heard and only those who have heard were further
      analyzed. The age range was from 16 to 47 yrs (mean age 27.1 +/- 3.3 years).
      Median parity was 2. One hundred and twenty two (54.2%) women had tertiary
      education. One hundred and seventy four (77.3%) correctly defined neonatal
      jaundice, and in 114 (44.7%) source of information was from health talk in the
      clinic. Seventy five (33.3%), and 50 (22.2%) erroneously believed that eating too
      much groundnut in pregnancy and mosquito bite respectively were the main causes
      while 55 (24.4%) correctly answered that it is due to mismatch of mother and
      baby's blood. Only a few knew that use of dusting powder on baby's cord,
      prematurity, and storing baby's clothes in camphor were risk factors for NNJ. One
      hundred and fourteen (50.7%) and 60 (26.7%), wrongly believed that exposure to
      sunlight and use of glucose drinks respectively were the main forms of treatment
      and 50 (22.2%) knew brain damage as a possible complication CONCLUSION: There is
      still misconception on the causes and risk factors and treatment of neonatal
      jaundice among our women. Also only a few women are reached by the health talk in
      the clinics. There is therefore urgent need for massive health enlightenment
      campaign.

PMID- 19764673
TI  - Challenges of managing paediatric abdominal trauma in a Nigerian setting.
AB  - BACKGROUND: The management of abdominal trauma (particularly blunt trauma) has
      undergone tremendous revolution in the last 30 years with significant reduction
      in morbidity and mortality in developed countries. The aim of this report is to
      highlight the challenges of managing abdominal trauma in children in Nigeria
      based on our experience in Zaria, northern Nigeria. METHOD: This is a
      retrospective review of 82 children managed for abdominal trauma from 1991 2002
      at the Ahmadu Bello University Teaching Hospital, Zaria, Nigeria. Information
      regarding demographics, mechanism of injury, haemodynamic status at presentation,
      clinical and radiologic evaluation, management, intraoperative findings and
      outcome, were extracted from case notes, operation notes and discharge summary
      notes. RESULTS: Fifty seven (69.5%) children had blunt trauma, mostly from
      traffic accidents (32, 57%) and falls (20, 36%), and 25 (30.5%) penetrating
      trauma mainly from falls onto sharp objects (7 of 18 patients) and animal-related
      injuries (5 of 18 patients). In the management of those with blunt trauma,
      advanced imaging modalities were usually not available and this resulted in an
      unnecessary laparotomy rate of 51% (laparotomy considered unnecessary because the
      patients remained haemodynamically stable after resuscitation and any
      intraperitoneal bleeding had stopped by the time oflaparotomy and no active
      operative measure was required to control bleeding). The management of
      penetrating trauma was more straightforward as this was guided by evidence of
      peritoneal penetration. Mortality from blunt trauma was 14.5% (8 of 55 patients)
      from exsanguinations before surgery 2, gastric perforation 3, hepatic laceration
      2 and splenic injury one. Mortality from penetrating trauma was 12% (3 of 25
      patients) from tetanus, overwhelming infection and haemorrhage respectively. The
      overall mortality from abdominal injury was 13.8% (11 of 80 patients) and were
      mostly avoidable if the patients presented early, and received some resuscitation
      before arrival at our hospital. CONCLUSION: The management of blunt abdominal
      trauma in children in Nigeria is faced with several challenges, which are mainly
      absence of an organised trauma system and lack of appropriate facilities. These
      need to be addressed in order to improve the care of these injuries.

PMID- 19764674
TI  - Myelomeningocoele in dizygotic twins.
AB  - BACKGROUND: Periconceptional use of folic acid can reduce a woman's risk of
      having a baby with a neural-tube defect and other congenital abnormalities.
      METHOD: Case reports of babies OO both males, who were delivered at term by
      emergency caesarean section by a 21 year old woman. At birth, both twins had
      neural tube defects, bilateral talipes equinovarusdeformity, bladder and bowel
      dysfunction. Twin one in addition had hydrocephalus and a ventriculoseptal heart
      defect (VSD). CONCLUSION: We advocate comprehensive neural tube defect (NTD)
      surveillance, a folic acidsupplementation program for high-risk women who have
      had a NTD-affectedpregnancy and a national folic acid education campaign for
      allwomen of reproductive age preconceptionally.

PMID- 19764675
TI  - Occurrence of anaplastic oligodendroglioma in a patient with Williams syndrome: a
      case report with analysis of mutational profile of tumor.
AB  - Williams syndrome is a rare congenital developmental disorder characterized by a
      constellation of distinctive facial dysmorphisms, mental retardation,
      cardiovascular anomalies, infantile hypercalcemia, delayed developmental
      milestones, dental and musculoskeletal anomalies and distinctive personality
      traits. A majority of patients with Williams syndrome exhibit a hemizygous micro
      deletion of chromosome 7q11.23, which is the locus of some 20-30 genes including
      the ELN gene that encodes the structural protein elastin. Chromosome 7q contains
      putative tumor suppressor genes and is one of the chromosomes that are frequently
      involved in chromosomal aberrations in human malignancies. A paucity of tumors
      (three) has been reported in the literature to occur in patients with Williams
      syndrome. We report a case of anaplastic oligodendroglioma that occurred in a 31
      year-old man with Williams syndrome. Mutational profiling by loss of
      heterozygosity analysis using a panel of polymorphic micro-satellite markers
      indicated combined deletion of chromosome 1p and 19q. We draw attention to this
      apparently rare or possibly under-reported occurrence of tumors in patients with
      Williams syndrome and suggest that Central Nervous System [CNS] tumors be
      considered as differential diagnoses in such patients when they present with
      unanticipated neurologic symptoms that are not attributable to those commonly
      associated with Williams syndrome.

PMID- 19764676
TI  - Small intestinal tubulovillous adenoma--case report and literature review.
AB  - Benign small intestinal tumour, though rare, have been reported. We report a case
      of sessile and extensive tubulovillous adenoma in a 13-year-old girl. She
      presented in a private hospital with three months history of abdominal pain,
      abdominal distension, vomiting, constipation, weight loss and anorexia.
      Significant findings on examination were weight loss, dehydration, and a huge
      smooth, not tender, mobile and indentable mass which extended from the left
      lumbar region to right iliac fossa. Visible peristalsis coursing from left to
      right was seen on the mass. Erect and supine plain abdominal x-rays revealed
      features of partial intestinal obstruction and abdominal ultrasound scan revealed
      dilated and hypertrophied bowel segment but could not say the bowel segment
      affected. The affected segment was found to be a 55cm portion of terminal ileum
      at operation which was resected due to hypertrophied proximal and collapsed
      distal segments, features in keeping with chronic intestinal obstruction, and
      ileo-ileal anastomosis done. Histology report was that of benign tubulovillous
      adenoma and the girl has enjoyed stable health for more than a year on close
      follow up in surgical outpatient clinic. This case highlights the unusual
      presentation and unusual gross nature of this small intestinal adenoma, which was
      found to be a benign adenoma on histological examination.

PMID- 19764677
TI  - Congenital hypothyroidism--a delayed diagnosis in a neonate. A case report.

PMID- 19764678
TI  - Traumatic diseases of parotid gland and sequalae. Review of literature and case
      reports.
AB  - Parotid gland injuries are accompanied by a large number of sequelae. The aim of
      this paper is to highlight the importance of thorough management of these parotid
      glandinjuries especially at initial presentation in order to minimize the
      complications that accompany these injuries. A review of the aetiology and
      management of the existing cases of parotid gland injuries obtained from
      published journals and internet search as well as a report of two cases managed
      in our centre is presented in this paper. A total of about 70 cases in the
      previous literatures were reviewed of which assault was responsible for almost
      90% of the cases. Sialoceles and fistulae were the main sequelae of these
      injuries. More than half of the cases (54%) were managed by conservative methods.
      Surgical drainage was done in about 44% cases; where the Stenson's ducts were
      accessible, primary repair was done. Excision of the gland was done in very few
      cases. The two cases managed in our centre were due to assault from broken
      bottles and road traffic accident respectively and both were managed by
      conservative methods. The first patient was a case of sialocele following the
      injury, which resolved within 3 weeks after the cyst formation with reduction in
      food intake, aspirations and external surgical drainage; while the second patient
      was a case of persistent fistula which healed after about 5 weeks following the
      trauma. Follow-up of both patients for about 3 months revealed no further leakage
      or accumulation of saliva. Management of these injuries involves a thorough
      understanding of the structure and function of the parotid gland and closely
      related tissues.

PMID- 19764679
TI  - Serum urea and uric acid concentration in pregnant women in sub-urban commercial
      community in Africa.
AB  - Serum uric acid and urea levels were determined in 27 pregnant and 17 non
      pregnant black African women. Uric acid levels for the pregnant women were
      significantly raised, and the relationship between uric acid elevation and
      gestational proteinuric hypertension was discussed. In conclusion, we recommend
      that uric acid estimation should be included during routine antenatal clinics in
      normal pregnancy. That the use of uric acid levels should be encouraged for the
      diagnosis and management of gestational proteinuric hypertension in African
      pregnant women. The above recommendation will help to reduce prenatal morbidity
      and mortality in African pregnant women.

PMID- 19764680
TI  - Primary papillary transitional cell carcinoma of the breast: a case report.
AB  - BACKGROUND: Primary papillary transitional cell carcinoma of the breast is a rare
      occurrence worldwide and few cases ever have been reported. It may be mistaken
      for the benign intraductal papillary lesions or papillary adnexal neoplasms. CASE
      REPORT: A 66 year old woman who presented with a recurrent right breast mass.
      Histopathologic studies confirmed a diagnosis of Primary Papillary Transitional
      cell carcinoma. CONCLUSION: The need for a high index of suspicion of primary
      papillary transitional cell carcinoma of the breast must be considered,
      especially in suspected benign intraductal papillary lesions to facilitate
      adequate and timely diagnosis and management of this lesion.

PMID- 19764681
TI  - Fracture of the penis. A report of two cases.
AB  - We present two cases of fracture of the penis in two young men at the extremes of
      the social strata the first an unemployed tailor while the other a practicing
      engineer. The first one was a bachelor while the other was married with children.
      In the first case, the fracture occurred during masturbation while in the second
      case it occurred during consensual intercourse with his wife on top. In the first
      case the fracture occurred at the base of the penis with associated rupture of
      the deep dorsal vein while in the second case it affected the mid-shaft with
      urethral rupture and blood at the tip of the penis at presentation. Both of them
      presented within two hours of their injuries with deformed, swollen and tender
      penis. Laubscher's subcoronal sleeve operation with evacuation of clots and
      repair of the tear with absorbable sutures to ensure a leak-proof repair was
      promptly performed with no complications. Both patients experienced spontaneous
      erection whilst in hospital even with indwelling catheter in place. The wife of
      the second case became pregnant six months after the repair. Counseling was
      successful with the engineer but was unsuccessful with the tailor-bachelor who
      continued with masturbation despite professional help. Though we published the
      first case of fracture of the penis in this centre almost a decade ago, we still
      found it necessary to report these new cases managed after we created awareness
      of this uncommon condition in our environment in order to highlight the
      presentations and the factors that influenced outcome.

PMID- 19764682
TI  - Severe idiosyncratic drug reaction (Lyells syndrome) after ingesting
      dihydroartemisinin.
AB  - Lyells syndrome also called Toxic epidermal necrolysis is the extreme form of
      idiosyncratic drug reaction that is called Steven Johnsons Syndrome: The
      condition results in an extensive loss of the skin with mucous membrane
      involvement. Lyells syndrome has been induced by many agents. The commonest agent
      in the literature being sulphonamides. However, in our search of the medical
      literature there was no report of dihydroarthemisinin as a cause of Lyells
      syndrome. We report three patients seen at two tertiary health institutions with
      Lyells syndrome after treatment for malaria with dihydroarthemisinin. This
      resulted from administration of dihydroarthemisinin with chloroquine in two
      patients and dihydroarthemisinin with Amodiaquine in one patient. The first
      patient was a seven year old child who developed 90% cutaneous involvement and
      died from hemorrhagic shock. The second was a 28 old female that developed a 76%
      body surface involvement and died from septicemia. The third patient was a
      pregnant 37 year old woman that developed 52% body involvement and died from
      septic shock. In these patients the earliest symptoms were not recognized and
      there was considerable delay before referral. In view of the recent WHO
      recommendation ofArthemisinin Combination Treatment (ACT) for malaria, we expect
      more cases of Steven Johnson Syndrome and Lyells syndrome from ACT treatment. The
      aim of this report is to raise the awareness of clinicians to this potentially
      fatal complication.

PMID- 19764683
TI  - Water beds for unconscious and bedridden patients necessary.

PMID- 19764684
TI  - Genetics of asthma: the road ahead.

PMID- 19764685
TI  - Community-centred approach for the control of Aedes spp. in a peri-urban zone in
      the Andaman and Nicobar Islands using temephos.
AB  - BACKGROUND: Chikungunya fever struck the Andaman and Nicobar Islands in July
      2006. From the entomological point of view, dengue and chikungunya are hard to
      control due to the high prevalence of Aedes aegypti in both urban and rural
      areas. Mobilizing communities for the control of Aedes aegypti has not been
      attempted in India. METHODS: We did a prospective observational feasibility study
      in one peri-urban locality (Brookshabad) to assess the Aedes spp. infestation and
      subsequently test the efficacy of a community-based approach to control Aedes
      aegypti. An Aedes infestation larval survey was done with the assistance of
      community volunteers using the single larval survey (SLS) technique. House index,
      container index and Breteau index reflecting the relative prevalence and
      infestation levels were estimated. Various information, education and
      communication (IEC) campaign tools were developed to disseminate information
      about the prevalent situation. Several talks were organized to sensitize and
      motivate the people to realize the problem and participate in solving it. A two
      pronged strategy, viz. environmental management through source reduction and anti
      larval campaign using temephos was adopted to combat Aedes infestation through
      community involvement. RESULTS: A total of 533 water-holding containers were
      searched for Aedes larvae, both indoors (188/533, 35.3%) and outdoors (345/533,
      64.7%) from 104 (104/235, 44.3%) premises. Of these, 109 containers (95% CI
      17.19%-24.03%) were found to support Aedes spp. larval breeding (20.45%). The
      Breteau index was 104.8%. Aedes aegypti predominated followed by Aedes
      albopictus. The most abundant water-holding containers supporting Aedes breeding
      were plastic, metal drums and cement tanks. These water-holding containers were
      targeted for temephos application by the community volunteers. Forty rounds of
      temephos applications were carried out during the study period. The number of
      containers supporting Aedes aegypti breeding reduced significantly within 1 month
      post-intervention by community volunteers. As a result the Breteau and house
      indices dropped from 104.8% to 2.7% and 44.23% to 2.6%, respectively. Thereafter,
      the indices remained at zero level till completion of the study. CONCLUSION:
      Larval indices indicate that Aedes aegypti is well established in peri-urban
      Brookshabad. Predominance of this mosquito species indicates infiltration into
      the peri-urban locality and beginning of displacement of Aedes albopictus.
      Epidemiologically, 3 categories of water-holding containers, viz. plastic, metal
      drums and cement tanks facilitate breeding of Aedes aegypti. Consequently,
      targeted source reduction as one way of selectively attacking the most important
      types of containers with temephos is feasible. Community involvement and
      networking with the residents allowed for a community-centred approach to combat
      Aedes aegypti infestation. As an outcome of this approach, the larval indices
      reduced significantly and remained low. We suggest that a control strategy
      emphasizing the use of temephos through a community-centred approach should be
      considered for these islands. However, close monitoring of this approach is
      warranted for long term sustainability.

PMID- 19764686
TI  - Career preferences of medical students who joined Grant Medical College, Bombay
      in 1957 and 1982.
AB  - BACKGROUND: Scant data are available on the career paths of Indian medical
      students. I wished to determine the career destinations of students who joined
      Grant Medical College, Bombay in 1982 and 1957, at 25 and 50 years, respectively,
      after having joined the medical school. METHODS: Questionnaire, telephone
      interview, e-mail response and personal interview were used to collect the data.
      I also collected emigration data for the students of the 1982 batch and sought to
      learn whether they were happy with their choice of career. RESULTS: Forty-nine of
      156 students of the 1982 batch and 49 of 84 students of the 1957 batch were
      abroad, at the 25- and 50-year stage, respectively. Most students (125 of 129)
      from the 1982 batch had no regrets about their choice of career. Most of those in
      India (94 of 106) worked entirely in the private health sector. Only 1 student
      from each batch was in basic research. CONCLUSION: At least one-fourth of
      students from the batch of 1982 and over half the students from the batch of 1957
      were abroad. Over 90% of those in India were in the private health sector and
      were happy with their choice of career.

PMID- 19764687
TI  - Hazardous alcohol use in rural southern India: nature, prevalence and risk
      factors.
AB  - BACKGROUND: There is a dearth of data on the hazardous use of alcohol in rural
      India. METHODS: We examined the nature, prevalence and factors associated with
      hazardous use of alcohol among men in a rural community in southern India. We
      used stratified sampling to select subjects from the Kaniyambadi block and
      employed 'AUDIT', a standard instrument, to assess the use of alcohol. RESULTS:
      The prevalence of life-time use, use in the past year and hazardous use of
      alcohol was 46.7%, 34.8% and 14.2%, respectively. Using Indian made foreign
      liquor (OR 20.51; 95% CI 8.81-47.75) and living in a village which brewed illicit
      alcohol (OR 2.82; 95% CI 1.39-5.72) were risk factors for hazardous use while
      education (OR 0.39; 95% CI 0.21-0.72) was protective. These factors remained
      significantly associated with hazardous use after adjusting for age and education
      using logistic regression. CONCLUSION: The relationship between the availability
      of illicit and commercial alcohol and its hazardous use suggests the need for an
      alcohol policy which takes into account health and economic issues and also
      implements the law to prevent the negative impact of problem drinking.

PMID- 19764688
TI  - Impact of quality of dietary fat on serum cholesterol and coronary heart disease:
      focus on plant sterols and other non-glyceride components.
AB  - Elevated serum low density lipoprotein (LDL) cholesterol is a strong risk factor
      for coronary heart disease; dietary as well as therapeutic regimens target
      reduction of serum LDL cholesterol to decrease the morbidity and mortality of
      coronary heart disease. The fatty acid composition of dietary fat has a marked
      impact on serum LDL cholesterol and other risk factors of diet-related chronic
      diseases (metabolic syndrome, diabetes and coronary heart disease). Besides fatty
      acids, which constitute > 95% of their content, fats in foods contain other fat
      soluble chemicals collectively called non-glyceride components. Sterols are a
      major part of the non-glyceride components of fats in plant foods and get
      concentrated in vegetable oils. Current evidence suggests that properly
      solubilized plant sterols or stanols incorporated in ester or free form in
      various food formulations effectively restrict the absorption of both dietary and
      biliary cholesterol causing 10%-14% reduction in serum LDL cholesterol in normal,
      hyperlipidaemic and diabetic subjects. The carotenoid-lowering effect of foods
      enriched with plant sterols can be corrected by increasing the intake of foods
      rich in carotenoids. The use of foods enriched with plant sterols as a part of a
      heart-healthy diet is recommended only after consulting a clinician. Recent
      studies strongly suggest that even smaller amounts of sterols available from
      natural plant foods and vegetable oils are important dietary components for
      lowering serum LDL cholesterol. Furthermore, some of the other non-glyceride
      components of food fats have one or more of the following functions-vitamin
      activity, serum LDL cholesterol-lowering and antioxidant activity. Since the
      hypocholesterolaemic and antioxidant effects ofa combination of the non-glyceride
      components may be more than their individual effects, increasing dietary plant
      sterols and non-glyceride components from natural plant foods and vegetable oils
      could provide an additional dietary means for prevention/correction of
      dyslipidaemia and increasing the antioxidant potential of human diets. The food
      based dietary guidelines recommended to ensure an optimal fat quality in the diet
      of Indians provide high levels of natural plant sterols and other health
      promoting non-glyceride components in addition to adequate absolute levels of
      individual fatty acids and their optimal balance. National policies to promote
      these dietary guidelines may contribute to the prevention of coronary heart
      disease and other diet-related chronic diseases.

PMID- 19764689
TI  - Smoking and mortality: data from India.

PMID- 19764690
TI  - Financial incentives for a smoke-free workplace.

PMID- 19764691
TI  - Evaluation of the liver using computed tomography scan.

PMID- 19764692
TI  - The teacher and the taught: medical education in India at the crossroads.
AB  - In a good medical teacher we would like to see a good doctor, a good teacher, a
      good orator and, overall, a good human being. Many teachers of yesteryears may
      not have had all these qualities but they had the ability to instil in the
      student's mind a sense of respect and a desire to learn. We now have more of the
      science and less of the art of teaching. We have failed to live by example.
      Modern-day consumerism and a single-minded approach to money, coaching classes,
      destruction of proper medical training by effectively removing internship and
      housemanship have made students apathetic with no desire to learn. We suggest
      that there are several ways by which the situation can be remedied including a
      system of mentoring, incentives and feedback.

PMID- 19764693
TI  - 'Swine flu' hits Scotland.

PMID- 19764694
TI  - The flying doctor.

PMID- 19764695
TI  - Tamil Nadu shows the way.

PMID- 19764696
TI  - AIDS at the margin: experiences and lessons from marginalized groups in India
      (part II).

PMID- 19764697
TI  - Neuroleptic malignant syndrome without withdrawal of levodopa.

PMID- 19764698
TI  - An educationist teaching healthcare professionals?

PMID- 19764699
TI  - Estimation of mechanical strength of unilamellar and multilamellar AOT/water
      vesicles and their rupture using micropipet aspiration.
AB  - Vesicles prepared from surfactant sodium dioctyl sulfosuccinate (AOT) were
      characterized by micropipet aspiration for determining membrane bending rigidity
      and area expansion modulus and mechanism of rupture. Unilamellar vesicles (ULV)
      and multilamellar vesicles (MLV) were studied. The mechanical properties
      calculated using micropipet aspiration for ULV were found to be 5-10 k(B)T, K(a)
      = 100 +/- 20 mN/m and for MLV were 8-15 k(B)T, K(a) = 120 +/- 30 mN/m. These
      properties fall with the range of lipid (PC) membrane measurements (values).
      However, the membrane rigidity of multilamellar vesicles was found to be
      approximately 3 times larger than that of unilamellar vesicles. The apparent area
      expansion moduli of multilamellar vesicles are of the order 1.4 times, sustained
      far greater areal strain before rupture compared to that of unilamellar vesicles.
      A dynamic structural change in MLV is demonstrated upon stress by micropipet
      aspiration. MLV at stress undergoes various stages of deformation. The
      fluctuation in size and shape of MLV led to separation of bilayers from the stack
      and decrease in vesicle diameter facilitating in formation of new equilibrium
      MLV, for it to sustain the specified membrane tension, a new mechanism that is
      demonstrated experimentally.

PMID- 19764700
TI  - Large-scale identification and quantification of covalent modifications in
      therapeutic proteins.
AB  - Covalent modifications on therapeutic proteins are traditionally monitored by
      chromatographic techniques, which quantify limited number of protein
      modifications at a time. In this report, computer algorithms for automated
      analyses of liquid chromatography/tandem mass spectrometry (LC/MS/MS) data for
      large-scale identification and quantification of known and unknown modifications
      are described. Peptide identification is achieved by comparing the experimental
      fragmentation spectrum to the predicted spectrum of each native or modified
      peptide. Peak areas of related peptide ions under their selected-ion
      chromatograms (SIC) are used for relative quantification of modified peptides. A
      matched window function is used to generate SIC for more reliable quantification.
      In an LC/MS/MS analysis of a tryptic digestion of an IgG2 monoclonal antibody,
      1712 peptide ions were identified with a false-discovery rate of approximately
      0.4%, and 227 modifications were identified and quantified. The accuracy of the
      mass spectrometry-based quantification is evaluated by comparing the abundance of
      different glycoforms determined by mass spectrometry to that determined by a
      fluorescence-based chromatography method. This large-scale method may potentially
      replace many chromatographic methods for assessing the quality attributes of
      therapeutic proteins.

PMID- 19764701
TI  - Local THz time domain spectroscopy of duplex DNA via fluorescence of an embedded
      probe.
AB  - We demonstrate that THz vibrational activity of a biopolymer can be measured
      locally, on the effective length scale for polar solvation, with an embedded
      molecular probe. For this purpose, the polarity probe 2-hydroxy-7-nitrofluorene
      was linked into a 13mer DNA duplex opposite an abasic site. The NMR solution
      structure shows that the fluorene moiety occupies a well-defined position in
      place of a base pair but can flip around the long axis on a millisecond time
      scale. Femtosecond optical pump-probe experiments are used to measure the time
      resolved Stokes shift of emission from the probe. The dynamic shifts for solution
      in H(2)O and D(2)O are quantified. Their difference is much larger than that
      expected for free water, implying that only bound water is observed. A weak 26
      cm(-1) spectral oscillation of the emission band is observed, which is not
      present when the probe is free in solution and is therefore caused by the
      supramolecular structure (DNA and hydration water).

PMID- 19764702
TI  - Error analysis for NMR polymer microstructure measurement without calibration
      standards.
AB  - We report an error analysis method for primary analytical methods in the absence
      of calibration standards. Quantitative (13)C NMR analysis of ethylene/1-octene
      (E/O) copolymers is given as an example. Because the method is based on a self
      calibration scheme established by counting, it is a measure of accuracy rather
      than precision. We demonstrate it is self-consistent and neither underestimate
      nor excessively overestimate the experimental errors. We also show the method
      identified previously unknown systematic biases in a NMR instrument. The method
      can eliminate unnecessary data averaging to save valuable NMR resources. The
      accuracy estimate proposed is not unique to (13)C NMR spectroscopy of E/O but
      should be applicable to all other measurement systems where the accuracy of a
      subset of the measured responses can be established.

PMID- 19764703
TI  - Electrochemical deposition-stripping analysis of molecules and proteins by online
      electrochemical flow cell/mass spectrometry.
AB  - A methodology for online preconcentration of analytes and their subsequent
      electrochemically induced delivery to an online electrospray mass spectrometer is
      introduced. The approach is based on electrodeposition of an active metallic
      layer, silver deposit in this particular case, subsequent specific accumulation
      of the target analyte by electrochemical or chemical means onto the active layer,
      and finally oxidative electrostripping of the conductive layer along with the
      supported analyte to an online mass spectrometer. We demonstrate the new concept
      by selective electrochemical deposition of homocysteine and other organothiols
      directly on the working electrode of a miniature flow cell. The same approach was
      extended to the conjugation of the target analyte (avidin as a test case) to a
      thiolated ligand (biotin in this case) that was electrodeposited on the silver
      coated surface. Electrostripping of the silver dissolves the target species and
      allows their delivery to an online ESI-MS. Furthermore, the dissolved silver ions
      promote ionization, and its characteristic isotopic pattern assists in the
      identification of the target analyte.

PMID- 19764705
TI  - Experimental and theoretical studies of the reaction of Rh+ with CS2 in the gas
      phase: thermochemistry of RhS+ and RhCS+.
AB  - The gas-phase reactivity of the atomic transition-metal cation rhodium, Rh(+),
      with CS(2) is investigated using guided-ion-beam mass spectrometry (GIBMS).
      Endothermic reactions forming RhS(+) and RhCS(+) are observed. Analysis of the
      kinetic energy dependence of the cross sections for formation of these two
      products yields the 0 K bond energies of D(0)(Rh(+)-S) = 2.61 +/- 0.12 eV and
      D(0)(Rh(+)-CS) = 2.66 +/- 0.19 eV. These compare favorably with quantum chemical
      calculations at the CCSD(T)/Def2TZVPP//B3LYP/Def2TZVPP and CCSD(T)/Def2TZVPP
      levels of theory, where the former is also used to explore the complete potential
      energy surface of the reaction. It is found that the reaction initially involves
      insertion of the rhodium cation into one of the CS bonds of CS(2), followed by
      metal ligand cleavages to form the two product channels. The formation of ground
      state RhS(+) products is spin-forbidden, whereas RhCS(+) formation is spin
      allowed. Crossing points between the triplet and quintet surfaces are located in
      the region of the SRh(+)(CS) intermediate, which suggests that coupling between
      the surfaces is reasonably efficient, consistent with experiment.

PMID- 19764704
TI  - Structural characterization of unsaturated phosphatidylcholines using traveling
      wave ion mobility spectrometry.
AB  - A number of phosphatidylcholine (PC) cations spanning a mass range of 400-1000 Da
      are investigated using electrospray ionization mass spectrometry coupled with
      traveling wave ion mobility spectrometry (TWIMS). A high correlation between mass
      and mobility is demonstrated with saturated phosphatidylcholine cations in N(2).
      A significant deviation from this mass-mobility correlation line is observed for
      the unsaturated PC cation. We found that the double bond in the acyl chain causes
      a 5% reduction in drift time. The drift time is reduced at a rate of
      approximately 1% for each additional double bond. Theoretical collision cross
      sections of PC cations exhibit good agreement with experimentally evaluated
      values. Collision cross sections are determined using the recently derived
      relationship between mobility and drift time in TWIMS stacked ring ion guide
      (SRIG) and compared to estimated collision cross sections using an empiric
      calibration method. Computational analysis was performed using the modified
      trajectory (TJ) method with nonspherical N(2) molecules as the drift gas. The
      difference between estimated collision cross sections and theoretical collision
      cross sections of PC cations is related to the sensitivity of the PC cation
      collision cross sections to the details of the ion-neutral interactions. The
      origin of the observed correlation and deviation between mass and mobility of PC
      cations is discussed in terms of the structural rigidity of these molecules using
      molecular dynamic simulations.

PMID- 19764706
TI  - Synthesis of anatase TiO(2) nanoshuttles by self-sacrificing of titanate
      nanowires.
AB  - Anatase TiO(2) nanoshuttles have been successfully prepared via a hydrothermal
      method under alkaline conditions by employing titanate nanowires as the self
      sacrificing precursors. The experimental results showed that a radical structural
      rearrangement took place from titanate wires to anatase TiO(2) shuttles during
      the hydrothermal reaction on the basis of a dissolution-recrystallization
      process. The surface of titanate nanowires plays a key role in the transformation
      process by providing both the structural units (e.g., TiO(6) octahedra) to
      realize anatase transformation and locations for the deposition and rearrangement
      of the dissolved structural units, while the formation of shuttle morphology is
      attributed to the minimization of surface energy with thermodynamically stable
      (101) facets of anatase TiO(2). The shape and phase transformation process were
      foundto be dependent on the hydrothermal reaction time. Raman and
      photoluminescence spectra confirmed the crystalline nature of the TiO(2)
      nanoshuttles.

PMID- 19764707
TI  - Isostructural bis-1,2,3-thiaselenazolyl dimers.
AB  - Reduction of the N-methylated bis-1,2,3-thiaselenazolylium salts [2a,b,c][OTf]
      (with R(1) = Me and R(2) = H (2a), F (2b), Me (2c)) affords the corresponding bis
      1,2,3-thiaselenazolyl radicals 2a,b,c. The radicals crystallize as
      centrosymmetric Se-Se sigma-bonded dimers [2a,b,c](2), in which an intramolecular
      Se-S bond of the radical is cleaved and replaced by an intermolecular Se-Se bond.
      The crystal structures of the three dimers are isomorphous, all belonging to the
      monoclinic space group P2(1)/c, and consist of interpenetrating, cross-braced,
      slipped pi-stack arrays laced together by numerous short intermolecular Se-N' and
      Se-S' contacts. In the solid state the dimers are diamagnetic, and behave as
      small band gap semiconductors with a room temperature conductivity sigma(RT) near
      10(-6) S cm(-1). Application of pressure leads to a dramatic increase in
      conductivity for all three compounds. At 5 GPa the value of sigma(RT) ranges from
      near 10(-1) S cm(-1) for [2c](2) to 1 S cm(-1) for [2b](2) and 10(1) S cm(-1) for
      [2a](2). Comparison of the three crystal structures suggests that the
      compressibility of [2a](2), and hence the response of its conductivity to
      pressure, is superior to that of [2b,c](2).

PMID- 19764708
TI  - Isoform-selective chemical inhibition of mDia-mediated actin assembly.
AB  - Formins are potent actin assembly factors. Diaphanous formins, including mDia1,
      mDia2, and mDia3 in mammals, are implicated in mitosis and cytokinesis, but no
      chemical interactors have been reported. We developed an in vitro screen for
      inhibitors of actin assembly by mDia1 and identified an inhibitor of mDia1 and
      mDia2 that does not inhibit mDia3 at the concentrations tested. These results
      establish the druggability of mDia formins and introduce a first-generation
      inhibitor.

PMID- 19764709
TI  - Fabrication of multiple concentric nanoring structures.
AB  - We present the fabrication of GaAs/AlGaAs Multiple (from three to five)
      concentric nanoring structures by an innovative growth method based on droplet
      epitaxy and characterized by short time As supply to the Ga droplets at different
      substrate temperatures. The formation mechanism has been interpreted on the basis
      of a detailed ex situ and in situ characterization of nanostructure morphology
      and surface reconstruction. We introduce design criteria which will allow to
      obtain concentric quantum ring structures of the desired complexity.

PMID- 19764710
TI  - Nitro-Mannich/lactamization cascades for the direct stereoselective synthesis of
      pyrrolidin-2-ones.
AB  - An efficient three-component nitro-Mannich/lactamization cascade of methyl 3
      nitropropanoate with in situ formed acyclic imines for the direct preparation of
      pyrrolidinone derivatives has been developed. The reaction is easy to perform,
      broad in scope, and highly diastereoselective and may be extended to cyclic
      imines allowing the direct formation of polycyclic pyrrolidinone derivatives.

PMID- 19764711
TI  - Palladium-catalyzed domino C,N-coupling/carbonylation/Suzuki coupling reaction:
      an efficient synthesis of 2-aroyl-/heteroaroylindoles.
AB  - A convenient one-pot synthesis of 2-aroylindoles using a domino palladium
      catalyzed C,N-coupling/carbonylation/C,C-coupling sequence is described. The
      reaction involved easily prepared 2-gem-dibromovinylanilines and boronic acids
      under carbon monoxide. Optimized reaction conditions allowed the construction of
      a wide variety of highly functionalized 2-aroyl-/heteroaroylindoles in
      satisfactory yields.

PMID- 19764712
TI  - Scalable synthesis of L-iduronic acid derivatives via stereocontrolled
      cyanohydrin reaction for synthesis of heparin-related disaccharides.
AB  - L-ido cyanohydrin 3 was prepared from diacetone-D-glucose in four steps and 76%
      overall yield and 90% de via cyanohydrin reaction of aldehyde 2. This process can
      be scaled to provide >1 mol of pure L-ido cyanohydrin 3. Cyanohydrin 3 was
      elaborated to 1,2-isopropylidine-protected L-ido nitrile (8), iduronic amide 9,
      and known carboxy ester 10. Coupling of 8 and 9 with glucosamine donors leads to
      new types (6-cyano and 6-carboxamide) of heparin-related disaccharides.

PMID- 19764713
TI  - Green method for the synthesis of highly substituted cyclohexa-1,3-diene,
      polyhydroindene, polyhydronaphthalene, isochromene, isothiochromene, and
      isoquinoline derivatives in ionic liquids.
AB  - An efficient and green method for the synthesis of highly substituted cyclohexa
      1,3-diene, polyhydroindene, polyhydronaphthalene, isochromene, isothiochromene,
      and isoquinoline derivatives has been developed. The synthesis was achieved by
      using a multicomponent procedure in ionic liquid media. The features of this
      procedure are characterized by the following: mild reaction conditions, high
      yields, one-pot procedures, operational simplicity, and environmentally benign
      conditions.

PMID- 19764714
TI  - Conjugated oligothienyl dendrimers based on a pyrazino[2,3-g]quinoxaline core.
AB  - The synthesis of a new series of conjugated dendrimers based on an electron
      accepting core is introduced. The compounds showed broad absorption bands over
      300-700 nm and have reduced HOMO-LUMO gaps of 1.7-1.9 eV. Incorporation of these
      compounds in bulk heterojunction solar cells as electron-donating material along
      with PC61BM as electron acceptor gave power conversion efficiencies of up to 1.3%
      for the second-generation dendrimer.

PMID- 19764715
TI  - Experimental and kinetic modeling evidences of a C7H6 pathway in a rich toluene
      flame.
AB  - The structure of a laminar, premixed, and one-dimensional toluene-oxygen-argon
      (9.9 mol % C(7)H(8), 44.5 mol % O(2), and 45.6 mol % Ar) flame, with an
      equivalence ratio of 2 and burning at 36 Torr was analyzed by gas chromatography
      and molecular beam mass spectrometry (MBMS). Mole fraction profiles of 25
      chemical species including permanent gases of combustion and first polycyclic
      aromatic hydrocarbons as naphthalene, methylnaphthalene isomers, biphenyl, and
      phenanthrene have been measured. A kinetic model based on recent literature data
      has been elaborated to compare with measurements. As suggested by recent
      theoretical studies, benzyl radical (C(7)H(7)) dissociation into fulvenallene
      (C(7)H(6)) + H and the reaction between C(7)H(6) and H giving cyclopentadienyl
      radical and acetylene have been included into the model. A comparison between
      experimental and predicted flame structures have allowed us to validate the
      kinetic model for rich toluene combustion. Moreover, MBMS measurements of mole
      fraction profiles corresponding to m/z ratios of C(7)H(7) and C(7)H(6) have
      permitted a specific validation of the theoretically postulated C(7)H(6) pathway
      in toluene flames.

PMID- 19764717
TI  - AuX3-mediated selective head-to-head dimerization of difluoropropargyl amides.
AB  - A dimerization of difluoropropargyl amides by reaction with gold(III) halides is
      described. A reductive elimination of a divinylgold species can be invoked to
      rationalize its formation. Initial studies of the unusual reactivity of these 1,4
      dihalo-1,3-dienes have been performed.

PMID- 19764716
TI  - Assembly with the Na,K-ATPase alpha(1) subunit is required for export of beta(1)
      and beta(2) subunits from the endoplasmic reticulum.
AB  - The level of the heterodimeric Na,K-ATPase is tightly controlled in epithelia to
      maintain appropriate transport function. The catalytic Na,K-ATPase alpha subunit
      is not able to exit the ER or catalyze ion transport unless assembled with the
      beta subunit. However, requirements for the ER exit of the Na,K-ATPase beta
      subunit that plays an additional, ion-transport-independent, role in
      intercellular adhesion are not clear. Exogenous beta(1) or beta(2) subunits
      expressed in renal MDCK cells replace endogenous beta(1) subunits in the alpha
      beta complexes in the ER, resulting in a decrease in the amount of the alpha(1)
      bound endogenous beta(1) subunits by 47-61% with no change in the amount of
      alpha(1) subunits. Disruption of the alpha(1)-beta association by mutations in
      defined alpha(1)-interacting regions of either beta(1) or beta(2) subunits
      results in the ER retention and rapid degradation of unassembled mutants. Hence,
      the ER quality control system allows export only of assembled alpha-beta
      complexes to the Golgi, thereby maintaining an equimolar ratio of alpha and beta
      subunits in the plasma membrane, whereas the number of alpha(1) subunits in the
      ER determines the amount of the alpha-beta complexes.

PMID- 19764718
TI  - Protecting-group-free synthesis of 3-tert-prenylated oxindoles: contiguous all
      carbon quaternary centers via tertiary neopentyl substitution.
AB  - Ruthenium-catalyzed tert-prenylation of isatin 1 occurs efficiently in the
      absence of N-protecting groups under the conditions of C-C bond-forming transfer
      hydrogenation employing 1,1-dimethylallene as the prenyl donor. The prenylated
      adduct, 3-hydroxy-3-tert-prenyl-oxindole 2, is converted to the tertiary
      neopentyl chloride 3, which participates in nucleophilic substitution by way of
      an aza-o-xylylene intermediate to furnish adducts 4a-4i. Through tertiary
      neopentyl substitution, two contiguous all-carbon quaternary centers are
      established.

PMID- 19764720
TI  - Preventing protein adsorption from a range of surfaces using an aqueous fish
      protein extract.
AB  - We utilize an aqueous extract of fish proteins (FPs) as a coating for minimizing
      the adsorption of fibrinogen (Fg) and human serum albumin (HSA). The surfaces
      include stainless steel (SS), gold (Au), silicon dioxide (SiO(2)), and
      poly(styrene) (PS). The adsorption processes (kinetics and adsorbed mass) are
      followed by quartz crystal microbalance with dissipation (QCM-D). Complementary
      surface information is provided by X-ray photoelectron spectroscopy (XPS) and
      atomic force microscopy (AFM). QCM-D shows no mass increases to any of the FP
      coated surfaces upon treating with Fg or HSA. Also, when Fg- or HSA-coated
      surfaces are exposed to the FPs, a significant increase in adsorbed mass occurs
      because the FPs are highly surface-active displacing Fg. Additionally,
      fluorescence microscopy confirms that very little Fg adsorbs to the FP-coated
      surfaces. We propose that FP coatings prevent protein adsorption by steric
      stabilization and could be an alternative method for preventing unwanted
      bioadhesion on medical materials.

PMID- 19764721
TI  - Catalytic asymmetric synthesis of palmerolide A via organoboron methodology.
AB  - A catalytic enantioselective synthesis of the antimelanoma marine natural product
      (-)-palmerolide A was accomplished using a longest sequence of 21 steps and
      without resorting to stoichiometric chiral auxiliaries or the chiral pool. The
      right half was constructed with a new variant of the Claisen-Ireland
      rearrangement exploiting an alkenylboronate as a masked hydroxyl. The left half
      featured the first application of a diol.SnCl(4)-catalyzed enantioselective
      crotylboration in the context of a complex target. This distinct strategy could
      pave the way to the design of simplified analogues of palmerolide.

PMID- 19764722
TI  - Fluorescent conjugated polymer nanoparticles by polymerization in miniemulsion.
AB  - Highly fluorescent conjugated polymer nanoparticles were prepared directly by
      polymerization in aqueous miniemulsion, employing Glaser coupling polymerization
      as a suitable step-growth reaction. A 4,4'-dinonyl-2,2'-bipyridine-modified
      catalyst was found to be suited for the polymerization in the aqueous heterophase
      system. Nanoparticles of poly(arylene diethynylenes) (arylene = 2,5-dialkyoxy
      phenylenes and 9,9'-dihexyl fluorene) with molecular weights in the range of M(n)
      10(4) to 10(5) g mol(-1) and with sizes of < or = 30 nm, as observed by TEM,
      result. N,N'-di(4-ethynylphenyl)-1,7-di[4-(1,1,3,3
      tetramethylbutyl)phenoxy]perylene-3,4:9,10-tetracarboxdiimide or 2,7
      diethynylfluorenone was converted completely during the heterophase
      polymerization to afford colloidally stable nanoparticles of poly(arylene
      diethynylenes) with 0.1-2 mol % covalently incorporated perylene dye and 2-9 mol
      % of covalently incorporated fluorenone dye, respectively. Fluorescence
      spectroscopy of the aqueous dispersions reveals an efficient energy transfer to
      the dye in the nanoparticles, which enables a variation of the luminescence
      emission color between red (lambda(em) (max.) ca. 650 nm) and the green emission
      of the nanoparticles without dye.

PMID- 19764719
TI  - Trafficking of heme and porphyrins in metazoa.

PMID- 19764723
TI  - Cell-directed localization and orientation of a functional foreign transmembrane
      protein within a silica nanostructure.
AB  - A simple procedure for introducing functional exogenous membrane-bound proteins
      to viable cells encapsulated within a lipid templated silica nanostructure is
      described. In one method, bacteriorhodopsin (bR) was added directly to a
      Saccharomyces cerevisiae solution along with short zwitterionic
      diacylphosphatidylcholines (diC(6) PC) and mixed with equal volumes of a sol
      precursor solution. Alternatively, bR was first incorporated into liposomes (bR
      proteoliposomes) and then added to an S. cerevisiae solution with diC(6) PC, and
      this was followed by mixing with sol precursor solution. Films prepared from bR
      added directly to diC(6) PC resulted in bR localization near S. cerevisiae cells
      in a disordered and diffuse fashion, while films prepared from bR-proteoliposomes
      added to the diC(6) PC/yeast solution resulted in preferential localization of bR
      near yeast cell surfaces, forming bR-containing multilayer vesicles. Importantly,
      bR introduced via proteoliposomes was observed to modulate pH gradients developed
      at the cell surface, demonstrating both retained functionality and preferential
      orientation. Localization of liposome lipid or bR did not occur around neutrally
      charged latex beads acting as cell surrogates, demonstrating that living cells
      actively organize the multilayered lipid during evaporation-induced self
      assembly. We expect this simple procedure for introducing functional and oriented
      membrane-bound proteins to the surface of cells to be general and adaptable to
      other membrane-bound proteins. This advance may prove useful in fundamental
      studies of membrane protein function and cell-cell signaling and in imparting non
      native characteristics to arbitrary cells.

PMID- 19764724
TI  - Iridium doped silica-PEG nanoparticles: enabling electrochemiluminescence of
      neutral complexes in aqueous media.
AB  - We report for the first time the stable electrochemiluminescence of a completely
      insoluble neutral Ir(III) complex in aqueous media. The strategy adopted is the
      encapsulation of emitting dye into silica-PEG nanoparticles. This nanoassembly by
      limiting water and oxygen quenching and allowing solubilization makes the
      electrogeneration of the excited state feasible under typical bioassay
      conditions.

PMID- 19764725
TI  - Bioapplications of RAFT polymerization.

PMID- 19764727
TI  - Phenolics metabolism in insects: Pieris brassicae-Brassica oleracea var. costata
      ecological duo.
AB  - Changes in the phenolics composition of Pieris brassicae larvae fasted for
      distinct periods (1, 2, 4, 6, and 8 h) and their excrements and of Brassica
      oleracea L. var. costata DC leaves were determined by high-pressure liquid
      chromatography/UV-photo diode array detector/mass spectrometry-electrospray
      ionization. This is the first report following phenolics' metabolism by P.
      brassicae through time. The results evidence that P. brassicae sequesters and
      metabolizes the phenolic compounds from the host plant. In a general way,
      deacylation was the main metabolic reaction that took place, but deglycosylation
      and sulfate conjugation reactions also occur. Additionally, several kaempferol
      derivatives containing rhamnose, which is not common in Brassica, were found in
      the host plant. Attending to the bioactivities recognized for the type of
      identified compounds, the different materials may constitute an interesting
      source of bioactive compounds, namely, of highly glycosylated and acylated
      kaempferol and quercetin derivatives, constituting an economic advantage for
      producers who have great losses caused by this pest. In addition, a deeper
      understanding of phenolics metabolism in insects was pursued.

PMID- 19764728
TI  - Abrasion as a catalyst deposition technique for carbon nanotube growth.
AB  - Mechanical abrasion of stainless steel (SS) surfaces is demonstrated as an
      effective technique for the deposition of catalyst to support growth of high
      density layers of carbon nanotubes (CNTs) in water-assisted catalytic chemical
      vapor deposition. In all cases of Fe-containing materials abraded on Al(2)O(3)
      substrates, CNT growth is observed; the 400 series of SS appears to deposit
      catalyst most efficiently. We demonstrate that this simple abrasion technique
      enables both micro- and nanoscale accuracy in catalyst patterning as well as
      large area catalyst deposition for uniform, dense CNT growth. Raman spectroscopy
      characterization indicates high quality CNTs grown by this approach. This
      technique provides an inexpensive and simple route for addition of catalyst for
      Fe-based surface growth of CNTs.

PMID- 19764729
TI  - Polymer-drug conjugates for combination anticancer therapy: investigating the
      mechanism of action.
AB  - We developed a family of polymer-drug conjugates carrying the combination of the
      anticancer agent epirubicin (EPI) and nitric oxide (NO). EPI-PEG-(NO)8, carrying
      the highest content of NO, displayed greater activity in Caco-2 cells while it
      decreased toxicity against endothelium cells and cardiomyocytes with respect to
      free EPI. FACS and confocal microscopy confirmed conjugates internalization.
      Light scattering showed formation of micelle whose size correlated with
      internalization rate. EPI-PEG-(NO)8 showed increased bioavailability in mice
      compared to free EPI.

PMID- 19764730
TI  - Halonium ion-assisted deiodination of styrene-based vicinal iodohydrins followed
      by rearrangement through phenyl migration.
AB  - Acid activation of bromate/bromide couple at 0-10 degrees C was found to trigger
      the deiodination of styrene-based vicinal iodohydrins. Violet coloration of the
      organic layer was ascribed to formation of IBr. Deiodination was followed by
      phenyl migration and deprotonation leading to formation of phenyl acetone and 2
      phenylpropanal in good yields from 1-iodo-2-phenylpropan-2-ol and 2-iodo-1
      phenylpropan-1-ol, respectively. Phenyl acetaldehyde--which was obtained in 92%
      GC yield from styrene iodohydrin--was also presumably formed in analogous manner.
      NBS and HOCl too were effective for transformation of styrene iodohydrin into
      phenyl acetaldehyde.

PMID- 19764731
TI  - Stereoselective synthesis of azetidines and pyrrolidines from N-tert
      butylsulfonyl(2-aminoalkyl)oxiranes.
AB  - Base-induced cyclization of enantiopure (2-aminoalkyl)oxiranes allowed the
      stereospecific formation of pyrrolidin-3-ols and/or 2-(hydroxymethyl)azetidines,
      depending on the reaction conditions. The oxidation of 2
      (hydroxymethyl)azetidines led to azetidine-2-carboxylic acids in high yields.

PMID- 19764732
TI  - An oxygen-sensing diguanylate cyclase and phosphodiesterase couple for c-di-GMP
      control.
AB  - A commonly observed coupling of sensory domains to GGDEF-class diguanylate
      cyclases and EAL-class phosphodiesterases has long suggested that c-di-GMP
      synthesizing and degrading enzymes sense environmental signals. Nevertheless,
      relatively few signal ligands have been identified for these sensors, and even
      fewer instances of in vitro switching by ligand have been demonstrated. Here we
      describe an Escherichia coli two-gene operon, dosCP, for control of c-di-GMP by
      oxygen. In this operon, the gene encoding the oxygen-sensing c-di-GMP
      phosphodiesterase Ec Dos (here renamed Ec DosP) follows and is translationally
      coupled to a gene encoding a diguanylate cyclase, here designated DosC. We
      present the first characterizations of DosC and a detailed study of the ligand
      dose response of DosP. Our results show that DosC is a globin-coupled sensor with
      an apolar but accessible heme pocket that binds oxygen with a K(d) of 20 microM.
      The response of DosP activation to increasing oxygen concentration is a complex
      function of its ligand saturation such that over 80% of the activation occurs in
      solutions that exceed 30% of air saturation (oxygen >75 microM). Finally, we find
      that DosP and DosC associate into a functional complex. We conclude that the
      dosCP operon encodes two oxygen sensors that cooperate in the controlled
      production and removal of c-di-GMP.

PMID- 19764733
TI  - pH-Controlled "off-on-off" switch based on Cu(2+)-mediated pyrene fluorescence in
      a PAA-SDS micelle aggregated supramolecular system.
AB  - We report herein the fluorescence response of pyrene in the presence of sodium
      dodecyl sulfate (SDS) micelle and poly(acrylic acid) (PAA) with Cu(2+) as an
      ionic quencher. Pyrene present in the PAA-SDS complex is quenched by Cu(2+) at pH
      approximately 2 ("off" state). Quenched pyrene emission is recovered at pH
      approximately 8 ("on" state). Due to easy protonation and deprotonation of the
      PAA chain in aqueous solution, this pH-controlled micellar ternary system
      exhibits a highly reversible "off-on-off" switch of the pyrene emission.

PMID- 19764734
TI  - Construction of multifunctional coatings via layer-by-layer assembly of
      sulfonated hyperbranched polyether and chitosan.
AB  - Layer-by-layer assembly has shown a great deal of promise in biomedical coatings,
      as well as local drug delivery systems. The poor loading capacity of hydrophobic
      drugs within the multilayers is a drawback in their potential applications.
      Herein, sulfonated hyperbranched polyether (HBPO-SO(3)) with a hydrophobic core
      was incorporated into LBL films to provide nanoreservoirs for hydrophobic guest
      molecules. HBPO-SO(3) was proven to form stable micelles in the sodium acetate
      and acetic acid buffer solution (HAc buffer) for LbL assembly. The QCM and
      ellipsometry experiments demonstrated that the LBL films can be fabricated via
      alternating deposition of HBPO-SO(3) micelles and chitosan. The fluorescence
      emission spectra verified that the hydrophobic pyrene can be incorporated both by
      pre-encapsulation in HBPO-SO(3) micelles and post-diffusion in preassembled
      multilayer films. Compared with the pre-encapsulation approach, the post
      diffusion process was more efficient in incorporating hydrophobic guest molecules
      into the LbL films and carried out a much more controllable release of the guest
      molecules. A multifunctional coating with potential anticoagulation,
      antibacterial, and local release of hydrophobic drug Probucal, which has powerful
      antioxidant properties and can prevent restenosis after coronary angioplasty, was
      then developed via post-diffusion of the anti-restenosis agents into the
      multilayer films of HBPO-SO(3) and chitosan.

PMID- 19764735
TI  - Chelation-assisted palladium-catalyzed direct cyanation of 2-arylpyridine C-H
      bonds.
AB  - A chelation-assisted palladium-catalyzed ortho-cyanation of the sp2 C-H bond by
      CuCN provided aromatic nitriles in moderate to good yields. Notably, the reaction
      could be conducted on a 10 mmol scale. The key intermediate of the natural
      product of Menispermum dauricum DC was concisely synthesized by the procedure.
      This new approach represents an exceedingly practical method for the synthesis of
      aromatic nitriles and offers an attractive alternative to the traditional
      Sandmeyer reaction.

PMID- 19764736
TI  - Stereoselective synthesis of the epicoccin core.
AB  - A short, convergent, and asymmetric synthesis of the epicoccin core was achieved
      using a phosphite-promoted one-step condensation of a complex proline-type amino
      acid. Key features of the assembly of this amino acid were a double-bond
      isomerization/vinylation/ring-closing metathesis strategy as well as an
      efficient, highly diastereoselective [2 + 2] cycloaddition of a ketene to an
      enecarbamate, derived from L-pyroglutamic acid.

PMID- 19764737
TI  - Efficient total synthesis of (-)-kaitocephalin.
AB  - A highly diastereoselective total synthesis of (-)-kaitocephalin, a novel
      antagonist of ionotropic glutamate receptors, was accomplished in 12 steps
      starting from 5-substituted proline ester via the aldol reaction with OBO-serine
      aldehyde, (E)-selective alpha,beta-dehydroamino acid synthesis using a new HWE
      reagent, and catalytic hydrogenation.

PMID- 19764738
TI  - Pressure-induced transformations in diborane: a Raman spectroscopic study.
AB  - As a classical electron-deficient molecule with unique hydrogen bridge bonding,
      diborane has created considerable interest in the structural chemistry. We report
      here the first evidence of pressure-induced structural transformations of
      diborane probed by in situ Raman spectroscopy. At pressures around 4 GPa,
      diborane undergoes a liquid-solid phase transformation to a new high-pressure
      phase I with a possible structure similar to the low-temperature phase. When
      compressed to above 6 GPa, the spectral features, such as doubling of the lattice
      modes, appearance of several new internal modes, and emergence of a new ring
      stretch mode, indicate the structural transformation to another new high-pressure
      phase II. This phase has a possible extended network structure of higher hydrides
      of borane. At pressures above 14 GPa, diborane transforms to yet another high
      pressure phase III. All of the observed pressure-induced structural
      transformations are completely reversible upon decompression.

PMID- 19764739
TI  - Role of surface conductivity in the dynamic mobility of concentrated suspensions.
AB  - In this article, a cell model is used for the evaluation of the alternating
      current (ac) mobility (dynamic mobility) of spherical particles in suspensions of
      arbitrary volume fractions of solids. The main subject is the consideration of
      the role of the electrical conductivity (SLC or K(sigmai)) of the stagnant layer
      (SL) on the mobility. It is assumed that the total surface conductivity
      (K(sigma)), resulting from both K(sigmai) and the diffuse layer conductivity
      (K(sigmad)), is constant in the cases considered and that it is the K(sigmai)
      K(sigmad) balance that determines the SL effects. We first explore the effect of
      K(sigmai) on the frequency dependence of the dynamic mobility. It is found that
      the mobility decreases on average, for any frequency, when K(sigmai) increases.
      This is a consequence of stagnancy: ions in the SL, although contributing to the
      surface conductivity, do not drag liquid with them when they migrate and do not
      contribute to electro-osmotic flow or, equivalently, to electrophoresis. Three
      relaxations are observed in the mobility-frequency spectrum: inertial (the
      particle and liquid motions are hindered), Maxwell-Wagner-O'Konski (ions in the
      double layer cannot follow the field oscillations and can move only over a
      distance much smaller that the diffuse layer thickness), and the so-called alpha
      or concentration polarization process (the ions can rearrange around the
      particle, but they cannot form the electrolyte concentration field that appears
      at low frequency). Whereas the first two relaxations are little affected by
      K(sigmai), the alpha process undergoes significant changes. Thus, the mobility
      increases with frequency around the alpha relaxation region if K(sigmai) is
      negligible, but it decreases with frequency in the same interval if K(sigmai) is
      finite. With the aim of explaining this behavior, we calculate the capillary
      osmosis velocity field that is the fluid flow provoked by the concentration
      gradient around the particle. The calculations presented demonstrate that the
      velocity is reduced (for each frequency and position) when the SLC is raised. It
      is proposed that such a decrease adds to that due to the changes in the induced
      dipole moment of the particle, also favoring a decrease in the mobility. These
      tendencies are also present when the volume fraction of solids, phi, is modified,
      although higher phi values somewhat hide the effect of K(sigmai), as in fact
      observed with all features of electrokinetics associated with the phenomenon of
      concentration polarization.

PMID- 19764740
TI  - Electrochemical determination of uranyl ions using a self-assembled monolayer.
AB  - Uranyl, UO(2)(2+), was electrochemically determined by a phosphate based self
      assembled monolayer. A pretreated gold electrode with 2-mercatpoethanol was
      chemically modified by POCl(3) or POBr(3) to obtain the surface phosphate active
      sites. The different stages were characterized by reflection-absorption Fourier
      transform-infrared (FT-IR) spectroscopy, capacity, and X-ray photoelectron
      spectroscopy (XPS). The electrochemical determination of UO(2)(2+) was
      accomplished, after preconcentration under open circuit potential, by square wave
      voltammetry.

PMID- 19764741
TI  - Discrimination of thioarsenites and thioarsenates by X-ray absorption
      spectroscopy.
AB  - Soluble arsenic-sulfur compounds play important roles in the biogeochemistry of
      arsenic in sulfidic waters but conflicting analytical evidence identifies them as
      either thioarsenates (= As(V)-sulfur species) or thioarsenites (= As(III)-sulfur
      species). Here, we present the first characterization of thioarsenates (mono-, di
      , and tetrathioarsenate) by X-ray absorption spectroscopy and demonstrate that
      their spectra are distinctly different from those of As(III)-sulfur species, as
      well as from arsenite and arsenate. The absorption near edge energy decreases in
      the order arsenate > thioarsenates > arsenite > As(III)-sulfur species, and
      individual thioarsenates differ by 1 eV per sulfur atom. Fitted As(V)-S and As(V)
      O bond distances in thioarsenates (2.13-2.18 A and 1.70 A, respectively) are
      significantly shorter than the corresponding As(III)-S and As(III)-O bond
      distances in As(III)-S species (2.24-2.34 A and 1.78 A, respectively). Finally,
      we demonstrate that thioarsenates can be identified by principal component
      analysis in mixtures containing As(III)-sulfur species. This capability is used
      to study the spontaneous reduction of tetrathioarsenate to As(III)-sulfur species
      (possibly trithioarsenite) upon acidification from pH 9.5 to 2.8.

PMID- 19764742
TI  - Reference measurement procedure development for C-reactive protein in human
      serum.
AB  - This paper describes the development of a reference measurement procedure to
      quantify human C-reactive protein (CRP) in serum using affinity techniques prior
      to tryptic digestion and liquid chromatography-tandem mass spectrometry (LC
      MS/MS) for the certification of reference materials in clinically relevant
      ranges. The absence of a suitable internal standard for the CRP measurement,
      necessary to eliminate potential measurement bias in both the affinity
      purification and trypsin digestion steps, was addressed using the method of
      standard addition. The standard addition quantification approach was combined
      with affinity purification, using an anti-CRP monoclonal antibody conjugated to
      polystyrene beads, trypsin digestion of the purified protein, and LC-MS/MS
      analysis of CRP tryptic peptides. The effectiveness of intact protein affinity
      purification was evaluated through the measurement of CRP in several serum-based
      CRP control materials, yielding levels that were comparable to their expected
      mean concentration values. Quantitative results were confirmed with an external
      calibration approach. This study demonstrates the feasibility of affinity
      purification with LC-MS/MS for the reference measurement procedure development of
      low abundance serum protein analytes.

PMID- 19764743
TI  - Detection of unintended stress effects based on a metabonomic study in tomato
      fruits after treatment with carbofuran pesticide. Capabilities of MCR-ALS applied
      to LC-MS three-way data arrays.
AB  - A chemometric strategy based on multivariate curve resolution and alternating
      least-squares (MCR-ALS) applied to LC-MS three-way data arrays has been developed
      to perform a metabonomic study in tomato (Lycopersicon esculentum) fruits
      (cultivar Rambo) following treatment with carbofuran. This methodology has proved
      to be adequate for the detection of unintended stress effects due to the previous
      treatment with this pesticide. MCR-ALS was performed on augmented matrices built
      with the LC-MS three-way data obtained from treated and nontreated samples
      through the sampling time. The strategy allowed us to obtain the concentration
      and spectra profiles of the main components (previously estimated with the SVD
      algorithm) from samples treated with pesticide as well as from blank samples,
      showing how they vary with time after plants treatment with the pesticide. In
      addition, a simple resolved mass spectrum was obtained corresponding to the peaks
      of a particular component in all matrices, thus avoiding ambiguity in the
      compound identity assignment. Different time profiles were found for some
      metabolites in treated and nontreated samples, which demonstrate that the
      presence of pesticide causes changes thorough time in the behavior of certain
      endogenous tomato metabolites as a result of physiological stress.

PMID- 19764744
TI  - Photo-cross-linking induces size change and stealth properties of water
      dispersible cinnamic acid derivative nanoparticles.
AB  - Hydrophilic poly(ethylene glycol) (PEG) was grafted onto poly(4-cinnamic acid)-co
      poly(3,4-cinnamic acid) (PCA) by Michael addition. The chemical structures of the
      PCA-graft-PEG (PCA-PEG) copolymers were confirmed by FT-IR and (1)H NMR
      measurements. The PCA-PEG nanoparticles were self-assembled by the solvent mixing
      method, in which additional water was dropped into a DMSO solution of the
      copolymer. The diameter of the PCA-PEG nanoparticles was below 100 nm, and
      decreased to about 30 nm upon increasing the composition ratio and molecular
      weight of PEG. The PCA-PEG nanoparticles showed [2 + 2] cyclobutane formation
      (cross-linking) following UV irradiation at lambda > 280 nm. Moreover, the photo
      cross-linking induced size decrement of the nanoparticles depending on the
      grafting degree and molecular weight of PEG. The amount of protein adsorption
      onto the surface of the nanoparticles was less than 30 ng/cm(2), due to the high
      density of PEG chains on their corona layers. Furthermore, photo-cross-linking
      induced a significant decrement in protein adsorption, due to an increase in PEG
      chain density triggered by the size decrement of the nanoparticles. These water
      dispersible and photoresponsive nanoparticles would be useful as novel,
      functional carriers for drug delivery systems and biological diagnosis.

PMID- 19764745
TI  - Target fishing for chemical compounds using target-ligand activity data and
      ranking based methods.
AB  - In recent years, the development of computational techniques that identify all
      the likely targets for a given chemical compound, also termed as the problem of
      Target Fishing, has been an active area of research. Identification of likely
      targets of a chemical compound in the early stages of drug discovery helps to
      understand issues such as selectivity, off-target pharmacology, and toxicity. In
      this paper, we present a set of techniques whose goal is to rank or prioritize
      targets in the context of a given chemical compound so that most targets against
      which this compound may show activity appear higher in the ranked list. These
      methods are based on our extensions to the SVM and ranking perceptron algorithms
      for this problem. Our extensive experimental study shows that the methods
      developed in this work outperform previous approaches 2% to 60% under different
      evaluation criterions.

PMID- 19764746
TI  - One-sample approach to determine the relative orientations of proteins in ternary
      and binary complexes from residual dipolar coupling measurements.
AB  - We present a procedure that supports the acquisition of (1)H-(15)N residual
      dipolar coupling (RDC) values for individual subunits in binary or ternary
      protein assemblies from a single experimental sample. Our method relies on
      asymmetric labeling of each subunit with the following scheme: species A
      uniformly with (15)N, species B uniformly with (15)N and (13)C, and species C
      uniformly with (15)N but selectively with (13)C' or (13)C(alpha). Because only a
      single sample is required, the approach obviates the need for preparing multiple
      samples and eliminates potential errors introduced from differences in sample
      conditions. Because numerous biological processes rely on protein assemblies or
      transient interactions, this method should be well suited for a wide range of
      future applications.

PMID- 19764747
TI  - Impact of nonnatural amino acid mutagenesis on the in vivo function and binding
      modes of a transcriptional activator.
AB  - Protein-protein interactions play an essential role in cellular function, and
      methods to discover and characterize them in their native context are of
      paramount importance for gaining a deeper understanding of biological networks.
      In this study, an enhanced nonsense suppression system was utilized to
      incorporate the nonnatural amino acid p-benzoyl-L-phenylalanine (pBpa) throughout
      the transcriptional activation domain of the prototypical eukaryotic
      transcriptional activator Gal4 in vivo (S. cerevisiae). Functional studies of the
      pBpa-containing Gal4 mutants suggest that this essential binding interface of
      Gal4 is minimally impacted by these substitutions, with both transcriptional
      activity and sensitivity to growth conditions maintained. Further supporting this
      are in vivo cross-linking studies, including the detection of a key binding
      partner of Gal4, the inhibitor protein Gal80. Cross-linking with a range of pBpa
      containing mutants revealed a Gal4 x Gal80 binding interface that extends beyond
      that previously predicted by conventional strategies. Thus, this approach can be
      broadened to the discovery of novel binding partners of transcription factors,
      information that will be critical for the development of therapeutically useful
      small molecule modulators of these protein-protein interactions.

PMID- 19764748
TI  - Decoration of gold nanoparticles on surface-grown single-walled carbon nanotubes
      for detection of every nanotube by surface-enhanced Raman spectroscopy.
AB  - An electroless deposition method comprised of seed formation and subsequent
      seeded growth is developed for the decoration of surface-grown single-walled
      carbon nanotubes (SWCNTs) with gold nanoparticles of controlled size and
      interparticle distance. The density of the gold nanoparticles is determined by
      the density of seeds. Gold seeds are used for the SWCNT arrays grown on SiO(x)/Si
      substrates. For the dense SWCNT arrays on quartz, palladium seeds are used
      because it is much easier to obtain higher quantities of seeds. Attributed to
      both the seed formation specified on SWCNTs and the succedent efficient seeded
      growth process, the gold nanoparticles deposit on SWCNTs with very high
      selectivity. This electroless method shows no selectivity on types, defects, and
      conductivity of the SWCNTs, and thus ensures the uniform decoration of all SWCNTs
      on the wafer. Most importantly, this method provides the possibility to realize
      the optimal configurations of gold nanoparticles on SWCNTs for obtaining maximal
      surface-enhanced effects and consequently surface-enhanced Raman spectrum (SERS)
      of each SWCNT. Thus, both the in situ Raman detection of every SWCNT including
      those nonresonant with laser energy and the observation of the radial breathing
      modes of SWCNTs originally undetectable with resonance Raman spectroscopy are
      achieved. Further investigations over the effect of the laser wavelength and the
      interparticle distance on the SERS enhancement factors of SWCNTs prove that the
      coupled surface plasmon resonance absorption of the high-density gold
      nanoparticles decorated on SWCNTs contributes most to the strong surface
      enhancement.

PMID- 19764749
TI  - Tunability of supramolecular Kagome lattices of magnetic phthalocyanines using
      graphene-based moire patterns as templates.
AB  - Self-assembly of various phthalocyanine (Pc) molecules and a derivative on an
      epitaxial graphene monolayer (MG) has been investigated by means of in situ
      ultrahigh vacuum scanning tunneling microscopy. The formation of regular Kagome
      lattices that duplicate the lattice of the moire pattern of MG was observed,
      demonstrating that MG can act as a wonderful template for the fabrication of
      unique nanoarchitectures with remarkable properties. Varying the central metal
      ion of the Pc molecule affords Kagome lattices with tunable molecular spins,
      providing ideal two-dimensional model systems for studying frustration physics.

PMID- 19764750
TI  - A delicate balance between sp2 and sp3 C-H bond activation: a Pt(II) complex with
      a dual agostic interaction.
AB  - 2-tert-Butyl-6-(4-fluorophenyl)pyridine reacts with K(2)PtCl(4) via the
      activation of an sp(2) C-H bond to give a cyclometalated complex that contains a
      bifurcated agostic interaction. Rearrangement of this complex results in the
      activation of an sp(3) C-H bond, and reaction eventually leads to a doubly
      cyclometalated complex where both sp(2) and sp(3) C-H bonds have been activated.
      Deuterium exchange studies show that a delicate balance exists between the two
      cyclometalations.

PMID- 19764751
TI  - Micelles for delivery of nitric oxide.
AB  - We designed block copolymer pro-amphiphiles and amphiphiles for providing very
      long-term release of nitric oxide (NO). A block copolymer of N-acryloylmorpholine
      (AM, as a hydrophile) and N-acryloyl-2,5-dimethylpiperazine (AZd, as a
      hydrophilic precursor) was synthesized. The poly(N-acryloyl-2,5
      dimethylpiperazine) (PAZd) is water-soluble, but chemical reaction of the
      secondary amines with NO to form a N-diazeniumdiolate (NONOate) converts the
      hydrophilic PAZd into a hydrophobic poly(sodium-1-(N-acryloyl-2,5
      dimethylpiperazin-1-yl)diazen-1-ium-1,2-diolate) (PAZd.NONOate), driving
      aggregation. The PAM block guides this process toward micellization, rather than
      precipitation, yielding ca. 50 nm spherical micelles. The hydrophobic core of the
      micelle shielded the NONOate from the presence of water, and thus protons, which
      are required for NO liberation, delaying release to a remarkable 7 d half-life.
      Release of the NO returned the original soluble polymer. The very small NO-loaded
      micelles were able to penetrate complex tissue structures, such as the arterial
      media, opening up a number of tissue targets to NO-based therapy.

PMID- 19764754
TI  - Swallow-tail substituted liquid crystalline perylene bisimides: synthesis and
      thermotropic properties.
AB  - Tailor-made synthesis and structure-property relationship of several swallow-tail
      N-substituted perylene bisimide (PBI) dyes are presented. PBI derivatives were
      synthesized by two distinct synthetic approaches, the details being evaluated
      herein. All the PBIs carry either alkyl swallow-tail or oligoethylenglycolether
      (OEG) swallow-tail moieties as N-substituents, and many of them are
      unsymmetrically substituted. We avoided substitution at bay positions of the
      perylene core to maintain the planarity and strong pi-pi interactions, which
      favor intermolecular order and charge carrier transport. The thermotropic
      behavior, which is strongly influenced by the nature of the substituents was
      investigated using differential scanning calorimetry (DSC), polarization optical
      microscopy (POM), and X-ray diffraction measurements (XRD). The introduction of
      OEG swallow-tail units facilitates thermotropic liquid crystalline behavior in
      most cases and the unsymmetrical substitution allowed the tuning of the mesophase
      width. The mesophases exhibit characteristic columnar hexagonal (Col(h)) packing
      arising from pi-pi interactions between cofacially orientated perylene molecules.
      Thus, the inherent tendency of PBI molecules for crystallization could be
      effectively suppressed by incorporating flexible OEG swallow-tail units only at
      imide positions. This molecular design was crucial to obtain liquid crystallinity
      and intracolumnar long-range order. The substituents did not influence the
      electronic energy levels such as HOMO and LUMO.

PMID- 19764755
TI  - A solid-state deuterium NMR and sum-frequency generation study of the side-chain
      dynamics of peptides adsorbed onto surfaces.
AB  - The artificial amphiphilic peptide LKalpha14 adopts a helical structure at
      interfaces, with opposite orientation of its leucine (L, hydrophobic) and lysine
      (K, hydrophilic) side chains. When peptides are adsorbed onto surfaces, different
      residue side chains necessarily have different proximities to the surface,
      depending on both their position in the helix and the composition of the surface
      itself. Deuterating the individual leucine residues (isopropyl-d(7)) permits the
      use of solid-state deuterium NMR spectroscopy as a site-specific probe of side
      chain dynamics. In conjunction with sum-frequency generation as a probe of the
      peptide-binding face, we demonstrate that the mobility of specific leucine side
      chains at the interface is quantifiable in terms of their surface proximity.

PMID- 19764756
TI  - Keeping the ball rolling: fullerene-like molecular clusters.
AB  - The discovery of fullerenes in 1985 opened a new chapter in the chemistry of
      highly symmetric molecules. Fullerene-like metal clusters, characterized by
      (multi)shell-like structures, are one rapidly developing class of molecules that
      share this shape. In addition to creating aesthetically pleasing molecular
      structures, the ordered arrangement of metal atoms within such frameworks
      provides the opportunity to develop materials with properties not readily
      achieved in corresponding mononuclear or lower-nuclearity complexes. In this
      Account, we survey the great variety of fullerene-like metal-containing clusters
      with an emphasis on their synthetic and structural chemistry, a first step in the
      discussion of this fascinating field of cluster chemistry. We group the compounds
      of interest into three categories based on the atomic composition of the cluster
      core: those with formal metal-metal bonding, those characterized by ligand
      participation, and those supported by polyoxometalate building blocks. The number
      of clusters in the first group, containing metal-metal bonds, is relatively
      small. However, because of the unique and complex bonding scenarios observed for
      some of these species, these metalloid clusters present a number of research
      questions with significant ramifications. Because these cores contain molecular
      clusters of precious metals at the nanoscale, they offer an opportunity to study
      chemical properties at size ranges from the molecular to nanoscale and to gain
      insights into the electronic structures and properties of nanomaterials of
      similar chemical compositions. Clusters of the second type, whose core structures
      are facilitated by ligand participation, could aid in the development of
      functional materials. Of particular interest are the magnetic clusters containing
      both transition and lanthanide elements. A series of such heterometallic clusters
      that we prepared demonstrates diverse magnetic properties including
      antiferromagnetism, ferrimagnetism, and ferromagnetism. Considering the diversity
      of their composition, their distinct electronic structures, and the disparate
      coordination behaviors of the different metal elements, these materials suggest
      abundant opportunities for designing multifunctional materials with varied
      structures. The third type of clusters that we discuss are based on
      polyoxometalates, in particular those containing pentagonal units. However,
      unlike in fullerene chemistry, which does not allow the use of discrete
      pentagonal building blocks, the metal oxide-based pentagonal units can be used as
      fundamental building blocks for constructing various Keplerate structures. These
      structures also have a variety of functions, including intriguing magnetic
      properties in some cases. Coupled with different linking groups, such pentagonal
      units can be used for the assembly of a large number of spherical molecules whose
      properties can be tuned and optimized. Although this Account focuses on the
      topological aspects of fullerene-like metal clusters, we hope that this topical
      review will stimulate more efforts in the exploratory synthesis of new fullerene
      like clusters. More importantly, we hope that further study of the bonding
      interactions and properties of these molecules will lead to the development of
      new functional materials.

PMID- 19764757
TI  - Effect of GC base pairs on charge transfer through DNA hairpins: the importance
      of electrostatic interactions.
AB  - DNA hairpins in which an electron donor and an electron acceptor are attached to
      the ends are excellent model systems for the study of charge transfer in weakly
      coupled pi-stacked systems. In this communication we report on a computational
      study of the effect of the base pair sequence in these DNA hairpins on the
      kinetics of charge transfer. We show that the rate of charge transfer strongly
      depends on the actual position of a GC base pair in a sequence that otherwise
      only contains AT base pairs. This can be explained by evaluating the energy
      landscape through which the charge travels. It is shown that including the
      electrostatic interaction between electron and hole can explain the
      experimentally observed dependence on the position of the GC in the DNA. We
      conclude that electrostatic interactions are important to consider when
      explaining the charge transfer kinetics in GC containing DNA sequences.

PMID- 19764758
TI  - Identification of two plastid proteins in the dinoflagellate Alexandrium affine
      that are substantially down-regulated by nitrogen-depletion.
AB  - The formation of harmful algal blooms (HABs) by dinoflagellates has been
      correlated with the nitrogen load in coastal waters. Nitrogen is implicated as an
      important factor in the initiation and maintenance of phytoplankton blooms. To
      characterize the cellular response to nitrogen, 2DE was used to compare protein
      expressions from dinoflagellates grown under nitrogen depleted and nitrogen
      replete conditions. A total of 17 differentially expressed protein spots were
      found, nine of which showed a roughly 16-fold decrease in N-depleted conditions.
      Five of these nine spots were all identified as isoforms of the plastid Form II
      ribulose-1,5 bisphosphate carboxylase/oxygenase (Rubisco II), while an additional
      four protein spots with a molecular weight of 50 kDa were identified as isoforms
      of a novel protein named nitrogen-associated protein 50 (NAP50). NAP50 was
      located in the plastids as shown by the presence of an N-terminal plastid
      targeting leader sequence and by immunohistochemistry. Levels of both Rubisco II
      and NAP50 decrease sharply between 24 and 36 h following nitrogen depletion and
      the decrease can be blocked if the N source is replenished before degradation
      occurs. Both proteins are rapidly resynthesized if the nitrogen source is
      replenished after degradation has occurred. These results are a first step in the
      dissection of the behavior of the dinoflagellate proteome under nitrogen stress
      conditions and may provide new insights into the relationship between
      dinoflagellate blooms and the nitrogen budget.

PMID- 19764759
TI  - Formal [4 + 2] cycloaddition of donor-acceptor cyclobutanes and aldehydes:
      stereoselective access to substituted tetrahydropyrans.
AB  - A highly diastereoselective synthesis of 2,6-cis-disubstituted tetrahydropyrans
      (THPs) via Lewis acid-catalyzed formal [4 + 2] cycloaddition of donor-acceptor
      cyclobutanes and aldehydes has been developed. THP products are formed in up to
      96% yield and 99:1 diastereoselectivity. Aromatic, cinnamyl, and aliphatic
      aldehydes are competent dipolarophiles in this system. This methodology was
      extended to a [[2 + 2] + 2] cycloaddition of 4-methoxystyrene, dimethyl
      methylidene malonate, and an aldehyde to furnish THPs directly without prior
      isolation of the cyclobutane.

PMID- 19764760
TI  - Quadrupole-central-transition 17O NMR spectroscopy of protein-ligand complexes in
      solution.
AB  - We report the first (17)O quadrupole-central-transition (QCT) NMR spectroscopic
      study of protein-ligand complexes in solution. This work shows that it is
      possible to obtain high resolution (17)O NMR spectra for (17)O-labeled ligands
      bound to proteins. At high magnetic fields such as 21.14 T, this (17)O QCT NMR
      approach should be applicable to studies of all oxygen-containing functional
      groups in large proteins (>30 kDa).

PMID- 19764761
TI  - Identification of the ADP-ribosylation sites in the PARP-1 automodification
      domain: analysis and implications.
AB  - Poly(ADP-ribose) polymerase-1 (PARP-1) is a multimodular (domains A, B, C, D, E,
      and F) nuclear protein that participates in many fundamental cellular activities.
      Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of
      the acceptor proteins and itself using NAD(+) as a substrate. Early studies
      suggested that domain D is likely an interface for protein-protein interaction
      between PARP-1 and its targets and is also the primary region for
      automodification. However, determination of the modification sites has been
      complicated by the heterogeneous nature of the poly(ADP-ribose) polymer. Here we
      report a strategy to identify the modification sites on domain D using the PARP-1
      E988Q mutant, which only catalyzes mono(ADP-ribosyl)ation. Trypsin digestion of
      the modified domain D followed by LC-MS/MS analysis led to the identification of
      three ADP-ribosylation sites in domain D (D387, E488, and E491). Our data also
      show, in contrast to early reports, that automodification of PARP-1 is not
      limited to domain D but occurs beyond this region. In addition, domain D is not
      essential for PARP-1 activity since PARP-1 mutant having domain D deleted is
      still catalytically active. Two synthetic peptides with amino acid sequences
      derived from the ADP-ribosylation sites of domain D were also demonstrated to act
      as PARP-1 substrates. The methodology and the results reported herein will
      facilitate future studies of PARP-1 catalysis.

PMID- 19764762
TI  - Spontaneous chirality induction and enantiomer separation in liquid crystals
      composed of achiral rod-shaped 4-arylbenzoate esters.
AB  - The discovery of spontaneously induced chirality and enantiomeric separation in
      liquid crystal and soft crystal systems composed of achiral rod-shaped 4
      arylbenzoate esters is described. Negligibly small circular dichroism (CD)
      signals are produced in the smectic A (SmA) phases of these substances, and the
      signals were found to increase with increasing smectic order. Since the advent of
      chirality occurs in freely suspended films, it is not a consequence of surface
      effects. Both positive and negative CD signals are observed with equal
      probability at different positions in these films. Vibrational CD spectroscopy
      and theoretical calculations are used to analyze the conformational changes that
      are associated with the induced chirality of the rod-shaped molecules. The
      results show that the phenomenon is caused by the twisting of biphenyl bond
      associated with the ester moiety in 4-arylbenzoate esters.

PMID- 19764763
TI  - Studies on the mechanism, selectivity, and synthetic utility of lactone reduction
      using SmI(2) and H(2)O.
AB  - Although simple aliphatic esters and lactones have long been thought to lie
      outside the reducing range of SmI(2), activation of the lanthanide reagent by
      H(2)O allows some of these substrates to be manipulated in an unprecedented
      fashion. For example, the SmI(2)-H(2)O reducing system shows complete selectivity
      for the reduction of 6-membered lactones over other classes of lactones and
      esters. The kinetics of reduction has been studied using stopped-flow
      spectrophotometry. Experimental and computational studies suggest that the origin
      of the selectivity lies in the initial electron-transfer to the lactone carbonyl.
      The radical intermediates formed during lactone reduction with SmI(2)-H(2)O can
      be exploited in cyclizations to give cyclic ketone (or ketal) products with high
      diastereoselectivity. The cyclizations constitute the first examples of ester
      alkene radical cyclizations in which the ester carbonyl acts as an acyl radical
      equivalent.

PMID- 19764764
TI  - Affinity-based screening of peptides recognizing assembly states of self
      assembling peptide nanomaterials.
AB  - Novel peptides capable of binding to self-assembled peptide nanomaterials were
      identified from a random heptapeptide library displayed on phages. Affinity
      dependent peptide screening against helically coiled nanofibers constructed of
      beta-sheet peptides gave phage clones displaying peptides with a variety of
      affinities and selectivities. An enzyme-linked immunosorbent assay using phage
      displayed peptides revealed that the screened peptides specifically bind to
      target nanofibers, in contrast to reference nanofibers comprised of peptides with
      slightly different amino acid sequences. A Dot blot assay using chemically
      synthesized peptides demonstrated that peptide 01 (p01), with the sequence Thr
      Gly-Val-Lys-Gly-Pro-Gly, showed an affinity constant (3.7 x 10(5) M(-1)) for the
      target nanofibers 200 times greater than its affinity for monomeric peptides and
      60 times greater than for short nanofibers. These results suggested that p01
      selectively recognizes the assembly state of the target peptide. ATR/IR secondary
      structure analyses clearly showed that when p01 binds to target nanofibers, it
      undergoes a structural transition from random-coil to parallel beta-sheet
      structures, resulting in greater affinity and high specificity for the target
      fiber. Surface modification of the peptide nanofibers by p01 demonstrated that
      the peptide specifically binds to the edge of the nanofibers. Using p01, uniform
      arrays of gold nanoparticles (proteins) could be generated on the peptide
      nanomaterials.

PMID- 19764765
TI  - Simulations of ICl-(CO2)n photodissociation: effects of structure, excited state
      charge flow, and solvent dynamics.
AB  - Experiments on the photodissociation of ICl(-) within size-selected CO(2)
      clusters [Nadal, M. E.; Kleiber, P. D.; Lineberger, W. C. J. Chem. Phys. 1996,
      105, 504.] differ from analogous experiments on homonuclear systems in two major
      ways: an early onset of caged, ICl(-)-based products with cluster size peaking at
      n = 5 and a rapid decline of caging after n = 5 in favor of dissociated, Cl(-)
      based fragments. Using an effective Hamiltonian model for the solute electronic
      structure and nonadiabatic MD trajectories, we have simulated the
      photodissociation of these clusters and found good agreement between experimental
      and simulated product distributions. The strong preference of the solvent for
      chlorine in the initial cluster structure, along with favorable kinematics, leads
      to the efficient caging at small n. At all cluster sizes, the Cl(-)-based
      fragments are formed by an adiabatic process and are accompanied by spin-orbit
      excited iodine. Caging of ICl(-) also occurs on the excited state potential
      surface, and electronic relaxation is not observed during the 100 ps
      trajectories. For n > 5, the initially caged products appear to be metastable,
      decaying to solvent-separated Cl(-)...I pairs that subsequently dissociate,
      leading to the falloff in the caging fraction in the larger clusters.

PMID- 19764767
TI  - Columnar structures from asymmetrically tapered biphenylamide.
AB  - An asymmetrically tapered N,N'-tris[[(2-dodecylaminocarbonyl)ethyl]methyl]-4
      biphenylamide (asym-C(12)PhA, where n is the number of carbon atoms in the alkyl
      chains, n = 12) was newly designed and synthesized. In this asymmetrically
      tapered asym-C(12)PhA biphenylamide, H-bondable hydrophilic amide moieties are
      located at between a rigid hydrophobic biphenyl rod and three flexible
      hydrophobic alkyl chains. Computer energy minimization indicated that three
      dimensional (3D) geometry of asym-C(12)PhA biphenylamide looks like a cone with
      dimensions of 3.01 nm in height and 1.44 nm in bottom radius. Phase transitions
      and supra-molecular structures were identified utilizing the combined techniques
      of differential scanning calorimetry, 1D wide-angle X-ray diffraction (1D WAXD),
      Fourier-transform infrared spectroscopy, and solid-state (13)C nuclear magnetic
      resonance analyses. The asym-C(12)PhA self-assembled into a highly ordered
      columnar mesophase just below the isotropization temperature and then transformed
      to 3D columnar crystalline phase (Phi(Cr)) on further cooling. Selected area
      electron diffractions in transmission electron microscopy (TEM) along with 1D
      WAXD and cross-polarized optical microscopy suggested that discotic building
      blocks were constructed by rotating 120 degrees of three asym-C(12)PhA with
      respect to neighboring ones and the tmb (top-middle-bottom) stacked discotic
      building blocks further self-organized into columns. These columns are laterally
      intercalated to form the Phi(Cr) phase. On the basis of the TEM image and
      polyethylene surface decoration technology, it was identified that the self
      assembled asym-C(12)PhA fibers with approximately 1 mum in diameter and several
      millimeters in length were braids of tiny single crystals.

PMID- 19764766
TI  - Intra-complex energy transfer of europium(III) complexes containing anthracene
      and phenanthrene moieties.
AB  - Laser excitation and luminescence studies were carried out for an ethanol
      solution of tris(hexafluoroacetylacetonato)europium(III), Eu(hfac)(3)(H(2)O)(2)
      (1), and n-hexane solutions of tris(hexafluoroacetylacetonato)europium(III) bis(9
      diisopropylphosphorylanthracene), Eu(hfac)(3)(DiPAnO)(2) (2), and
      tris(hexafluoroacetylacetonato)europium(III) bis(2
      diisopropylphosphorylphenanthrene), Eu(hfac)(3)(DiPPheO)(2) (3). The absorption
      spectra of 2 and 3 in n-hexane are interpreted by assuming that the central
      Eu(III) ion weakly interacts with the DiPAnO and DiPPheO moieties. The emission
      spectroscopic studies revealed that (1) Eu(hfac)(3)(DiPAnO)(2) emits only
      fluorescence from the DiPAnO moiety and (2) Eu(hfac)(3)(DiPPheO)(2) gives
      luminescence from the central Eu(III) ion, and (3) Eu(hfa)(3)(H(2)O)(2) and
      Eu(hfac)(3)(DiPPheO)(2) afford emission from both the (5)D(1) and (5)D(0) states
      of the Eu(III) ion upon 355 nm laser excitation. The intracomplex energy transfer
      processes are presented on the basis of absorption, emission and laser excitation
      studies.

PMID- 19764768
TI  - Cold incineration of chlorophenols in aqueous solution by advanced
      electrochemical process electro-Fenton. Effect of number and position of chlorine
      atoms on the degradation kinetics.
AB  - This study reports the kinetics of the degradation of several chlorophenols
      (CPs), such as monochlorophenols (2-chlorophenol and 4-chlorophenol),
      dichlorophenols (2,4-dichlorophenol and 2,6- dichlorophenol), trichlorophenols
      (2,3,5- trichlorophenol and 2,4,5-trichlorophenol), 2,3,5,6-tetrachlorophenol,
      and pentachlorophenol, by the electro-Fenton process using a carbon felt cathode
      and a Pt anode. The effect of number and the position of the chlorine atoms in
      the aromatic ring on the oxidative degradation rate was evaluated and discussed.
      The oxidation reaction of all the CPs with hydroxyl radicals evidenced a pseudo
      first-order kinetics and the rate constant decreased with increasing the number
      of chlorine atoms. The absolute rate constant of second-order reaction kinetics
      between CPs and (*)OH was determined by the competition kinetics method in the
      range of (3.56-7.75) x 10(9) M(-1) s(-1) and follows the same sequence of the
      apparent rate constants. The mineralization of several CPs and of a mixture of
      all CPs under study was monitored by the total organic carbon (TOC) removal and
      the chlorine release during mineralization was followed by ion chromatography.
      Our results demonstrated that more chlorinated phenols are more difficult to
      mineralize; however for all the tested CPs, almost quantitative release of
      chloride ions was obtained after 6 h of treatment.

PMID- 19764769
TI  - Large photoinduced circular dichroism in chiral polyfluorene.
AB  - At 77 K, thermally annealed films of chiral poly[9,9-bis((3S)-3,7-dimethyloctyl)
      2,7-fluorene] show a photoinduced absorption (PIA) band near 1.5 eV due to a
      transition from the lowest triplet state to a higher triplet state. This
      photoinduced absorption is found to show circular dichroism (CD). Dividing this
      CD by the magnitude of the PIA, we find that the selectivity for absorption of
      left circular polarized light over right circularly polarized light is remarkably
      high and characterized by a dissymmetry ratio g = +0.2. The unusual magnitude of
      g is interpreted as arising from extrinsic CD, i.e., from the interaction of the
      local linear polarization of the triplet-triplet absorption with the linear
      birefringence of the surrounding polymer matrix.

PMID- 19764770
TI  - Vibrationally resolved photoelectron spectroscopy of di-gold carbonyl clusters
      Au2(CO)n- (n = 1-3): experiment and theory.
AB  - We report vibrationally resolved photoelectron spectroscopy (PES) of
      Au(2)(CO)(n)(-) (n = 1-3), in combination with relativistic density functional
      theory (DFT) and ab initio calculations. The ground-state transition in the
      spectrum of Au(2)CO(-) is broad, containing vibrational structures both in the
      bending and in the CO stretching modes and suggesting a large structural change
      from Au(2)CO(-) to Au(2)CO. The ground-state transitions for both n = 2 and 3
      display a well-resolved vibrational progression in the CO stretching mode with
      frequencies of 2110 +/- 40 and 2160 +/- 40 cm(-1), respectively. The PES data
      show that chemisorption of the first two CO's each induces a significant red
      shift in the electron binding energies. The third CO is physisorbed, inducing
      only a slight increase in electron binding energies relative to Au(2)(CO)(2)(-).
      Relativistic DFT and ab initio calculations are performed to determine the ground
      state structures for Au(2)(CO)(n)(-) and Au(2)(CO)(n), and the results agree well
      with the experiment. Au(2)(CO), Au(2)(CO)(2), and Au(2)(CO)(2)(-) are all found
      to be linear, while Au(2)(CO)(-) is bent due to the Renner-Teller effect. A
      strong spin-orbit effect is found in Au(2)(CO)(2)(-) that quenches the Renner
      Teller effect, keeping the linear structure for this anion. The physisorption in
      Au(2)(CO)(3)(-) is borne out in CCSD(T) calculations. However, a wide range of
      DFT methods tested fail to correctly predict the relative energies of the
      physisorbed versus chemisorbed isomers for Au(2)(CO)(3)(-).

PMID- 19764772
TI  - Size dependence of tracer diffusion in a laponite colloidal gel.
AB  - Using a fluorescence recovery after photobleaching (FRAP) technique, we present
      measurements of probe diffusion in a colloidal glass-a Laponite suspension. By
      varying the probe size over 2 orders of magnitude, as well as the concentration
      of the colloidal glass, we evidence and quantify the deviations of the probe
      diffusivity from the bulk Stokes-Einstein expectations. These experiments suggest
      that the probe diffusion in the dynamically arrested Laponite structure is mainly
      controlled by the ratio between the probe size and the typical clay platelets
      interdistance. Comparing with a simple hindered diffusion mechanism, the
      reduction of tracer diffusion is discussed in terms of the hydrodynamic
      interaction of the probe with the Laponite structure. Finally, these results can
      be interpreted in terms of a scale dependent viscosity of the colloidal glass.

PMID- 19764771
TI  - Anxa2 plays a critical role in enhanced invasiveness of the multidrug resistant
      human breast cancer cells.
AB  - Multidrug resistance (MDR) is the major cause of failure in cancer chemotherapy.
      Recent reports even suggest that MDR is associated with elevated invasion and
      metastasis of tumor cells. In the current study, we used a proteomic approach to
      identify genes that play an important role in MDR induced cell migration. 2D-PAGE
      and MALDI-TOF/MS-based proteomics approach were used to separate and identify
      differentially expressed proteins between MCF-7 and MCF-7/ADR, a p-glycoprotein
      overexpressing adriamycin-resistance breast cancer cell line. Annexin a2 (Anxa2)
      was identified as highly expressed in MCF-7/ADR cells, but not in MCF-7 cells.
      Small interference RNA-mediated gene suppression demonstrated that Anxa2 was
      required for enhanced cell proliferation and invasion of the MCF-7/ADR cells.
      Down-regulation of Anxa2 alone was not sufficient to revert the cell sensitivity
      to adriamycin, suggesting that Anxa2 was not required for MDR phenotype. Taken
      together, our results showed that expression of Anxa2 is enhanced when cancer
      cells, MCF-7, acquired drug resistance and it plays an essential role in MDR
      induced tumor invasion.

PMID- 19764773
TI  - Phosphorylation of photosynthetic antenna protein CP29 and photosystem II
      structure changes in monocotyledonous plants under environmental stresses.
AB  - Kinetic studies of protein dephosphorylation in thylakoid membranes showed that
      the minor light-harvesting antenna protein CP29 could be phosphorylated in barley
      (C3) and maize (C4) seedlings, but not in spinach under water [Liu, W. J., et al.
      (2009) Biochim. Biophys. Acta 1787, 1238-1245], salt, or cold stress [Pursiheimo,
      S., et al. (2003) Plant Cell Environ. 26, 1995-2003], suggesting that
      phosphorylation of CP29 is a general phenomenon in monocots, but not in dicots
      under environmental stresses. Abscisic acid (ABA), reactive oxygen species (ROS),
      salicylic acid (SA), jasmonic acid (JA), ethylene (ET), NO, and the scavenger of
      H(2)O(2) had weak effects on CP29 phosphorylation. However, three protein kinase
      inhibitors, U0126, W7, and K252a (for mitogen-activated protein kinase, Ca(2+)
      dependent protein kinase, and Ser/Thr protein kinases, respectively), decrease
      the level of CP29 phosphorylation in barley apparently under environmental
      stresses. Therefore, these three protein kinases are involved in CP29
      phosphorylation. We also found that most CP29 phosphorylation was accompanied by
      its lateral migration from granum membranes to stroma-exposed thylakoid regions,
      and the instability of PSII supercomplexes and LHCII trimers under environmental
      stresses.

PMID- 19764774
TI  - Relaxation processes of PGPR at the water/oil interface inferred by oscillatory
      or transient viscoelasticity measurements.
AB  - The rheological properties of PolyGlycerol PolyRicinoleate (PGPR) at the
      oil/water interface were studied using a drop-shaped tensiometer. Small
      deformation oscillations of the drop area allow the measurement of the
      interfacial viscoelasticity spectrum, that is, the elastic and viscous moduli as
      a function of frequency. Another way to obtain such a spectrum is to perform a
      transient relaxation measurement from which the relaxation modulus as a function
      of time is deduced and interpreted. Several models containing one or more
      relaxation times were considered, and their resulting spectra were compared to
      the oscillatory ones. Similar results suggest that one could in principle use
      oscillatory or transient relaxations indifferently. However, the transient
      relaxation technique proved to be more adapted for the determination of the
      relaxation times. At low PGPR concentrations in oil, the behavior is controlled
      by long relaxation times, whereas short ones take over when approaching and
      exceeding the saturation interfacial concentration. This was understood as a
      shift from a diffusion-dominated regime to a rearrangements-dominated regime.

PMID- 19764775
TI  - Wound exudate as a proteomic window to reveal different mechanisms of tissue
      damage by snake venom toxins.
AB  - In light of the complexity of wound tissue, proteomic analysis may not clearly
      reveal the nature of the wound or the processes involved in healing. However,
      exudate associated with wounds may provide a "window" on cellular events leading
      to the development of the wound and/or its healing. In this investigation we
      performed proteomic analysis on wound exudates from muscular wounds in mice
      caused by two very different types of snake venom toxins: BaP1, a snake venom
      metalloproteinase and Mtx-I, a snake venom phospholipase A2. Proteomic analysis
      of the exudates associated with these wounds clearly differentiated them and
      offered new perspectives on functional mechanisms by which these toxins cause
      tissue damage. In the case of wounds caused by the metalloproteinase, there was
      evidence of degradation of nonfibrillar collagens whereas the phospholipase wound
      exudate was noted by the presence of fibrillar collagen type I, apolipoproteins A
      I, A-IV, and E, and fibronectin. These results suggest that the hemorrhage caused
      by snake venom metalloproteinases may be associated with the degradation of
      specific extracellular matrix proteins which play a role in matrix/capillary
      stabilization and that release of apolipoproteins from their complexes may be
      involved with the dysfunctional hemostasis observed following snake envenoming.

PMID- 19764776
TI  - SherLoc2: a high-accuracy hybrid method for predicting subcellular localization
      of proteins.
AB  - SherLoc2 is a comprehensive high-accuracy subcellular localization prediction
      system. It is applicable to animal, fungal, and plant proteins and covers all
      main eukaryotic subcellular locations. SherLoc2 integrates several sequence-based
      features as well as text-based features. In addition, we incorporate phylogenetic
      profiles and Gene Ontology (GO) terms derived from the protein sequence to
      considerably improve the prediction performance. SherLoc2 achieves an overall
      classification accuracy of up to 93% in 5-fold cross-validation. A novel feature,
      DiaLoc, allows users to manually provide their current background knowledge by
      describing a protein in a short abstract which is then used to improve the
      prediction. SherLoc2 is available both as a free Web service and as a stand-alone
      version at http://www-bs.informatik.uni-tuebingen.de/Services/SherLoc2.

PMID- 19764777
TI  - Adsorption and desorption of cationic surfactants onto silica from toluene
      studied by ATR-FTIR.
AB  - The adsorption and desorption behavior of cationic dialkyldimethylammonium
      bromide surfactants (Di-CnDABs where n = 10, 12, 14) at the silica-toluene
      interface has been studied. Adsorption is a rapid process, consistent with
      transport control, whereas desorption appears to occur in a two-stage process,
      with varying proportions of surfactant desorbing in fast and slow modes. These
      proportions appear to be affected by trace moisture present in the adjacent
      toluene solvent, possibly owing to competition between surfactant and water
      molecules for surface sites. Surprisingly, the surfactant tail length (n) has a
      significant impact on solubility in toluene, and this appears to affect bulk
      surface partitioning. The results are compared with previous experiments
      utilizing nonionic surfactants (Tabor, R. F.; Eastoe, J.; Dowding, P. Langmuir
      2009, 25, 9785), and also with work on surfactant-stabilized silica in nonpolar
      solvents (Tabor, R. F.; Eastoe, J.; Dowding, P. J.; Grillo, I.; Heenan, R. K.;
      Hollamby, M. Langmuir 2008, 24, 12793). Observations are explained in terms of
      the balance of interactions between the surfactant, solvent, and surface.

PMID- 19764778
TI  - Protein resistance of PNIPAAm brushes: application to switchable protein
      adsorption.
AB  - Protein adsorption, as the primary process occurring when a foreign surface comes
      into contact with a biosystem, was studied on thin polymer brush films consisting
      of poly(N-isopropylacrylamide) (PNIPAAm) and poly(2-vinylpyridine) (P2VP). These
      films were prepared by the "grafting to" method. The protein resistance of
      stimuli responsive PNIPAAm-brushes toward serum albumin was recorded and compared
      with protein adsorption on P2VP brushes. To achieve a better understanding of
      protein resistance, PNIPAAm brushes with different molecular weights were
      investigated below and above the lower critical solution temperature of 32
      degrees C. To use these findings for the adjustment and switching of protein
      adsorption, in a first attempt the adsorption on a mixed brush system consisting
      of PNIPAAm and P2VP chains was studied. This system showed temperature-dependent
      adsorption behavior due to the presence of PNIPAAm, representing a smart surface
      with stimuli-responsive changes in the physicochemical surface properties. With
      this mixed brush, the adsorbed amount of protein could be controlled, depending
      on composition and the temperature of the surroundings.

PMID- 19764779
TI  - Fluorescence emission of Disperse Red 1 in PS-b-P4VP micelles controlled by a
      toluene/ethanol solvent mixture.
AB  - The effects of Disperse Red 1 (DR1) in the poly(styrene-block-4-vinylpyridine)
      (PS-b-P4VP) micelle on micellar morphology and fluorescence emission were studied
      using small-angle X-ray scattering (SAXS), generalized indirect Fourier transform
      (GIFT), Fourier transform infrared (FT-IR), transmission electron microscopy
      (TEM), and photoluminescence (PL). PS-b-P4VP was coupled with DR1 in 10 mg/mL
      toluene/ethanol mixture solutions where ethanol and toluene were P4VP and PS
      selective, respectively. Hydrogen bonds were formed between the -OH group of DR1
      and the pyridine ring in PS-b-P4VP. DR1 (which was coupled with P4VP) was
      confined in the core or corona of the micelle depending on the location of P4VP.
      The micellar structure was strongly dependent on varphi (weight percentage of
      toluene in a toluene/ethanol mixture). The PS-b-P4VP-DR1 complex in the mixture
      solutions showed the spherical micelle with the cores of P4VP and PS in ethanol
      rich and toluene-rich solvents, respectively. The quenching phenomenon was
      observed for DR1 in the corona of PS-b-P4VP micelles [at varphi = 0 (ethanol)],
      while the fluorescence quantum yield decreased. However, significant increases in
      the fluorescence quantum yields at varphi = 100 were observed when DR1 was
      confined in the core of the PS-b-P4VP micelles. The confinement of DR1 in the
      hard core was more effective in fluorescence emission than that in the soft
      corona due to the slow trans-to-cis transition of DR1.

PMID- 19764780
TI  - Variability analysis of human plasma and cerebral spinal fluid reveals
      statistical significance of changes in mass spectrometry-based metabolomics data.
AB  - Analytical and biological variability are issues of central importance to human
      metabolomics studies. Here both types of variation are examined in human plasma
      and cerebrospinal fluid (CSF) using a global liquid chromatography/mass
      spectrometry (LC/MS) metabolomics strategy. The platform shows small analytical
      variation with a median coefficient of variation (CV) of 15-16% for both plasma
      and CSF sample matrixes when the integrated area of each peak in the mass spectra
      is considered. Analysis of biological variation shows that human CSF has a median
      CV of 35% and plasma has a median CV of 46%. To understand the difference in CV
      between the biofluids, we compared plasma and CSF independently obtained from
      different healthy humans. Additionally, we analyzed another group of patients
      from whom we compared matched CSF and plasma (plasma and CSF obtained from the
      same human subject). A similar number of features was observed in both biofluids,
      although the majority of features appeared with greater intensity in plasma. More
      than a dozen metabolites shared between the human CSF and plasma metabolomes were
      identified based on accurate mass measurements, retention times, and MS/MS
      spectra. The fold change in these metabolites was consistent with the median
      biological CV determined for all peaks. The measured median biological CV
      together with analysis of intragroup variation of healthy individuals suggests
      that fold changes above 2 in metabolomics studies investigating plasma or CSF are
      statistically relevant with respect to the inherent variability of a healthy
      control group. These data demonstrate the reproducibility of the global
      metabolomics platform using LC/MS and reveal the robustness of the approach for
      biomarker discovery.

PMID- 19764781
TI  - Electronic properties of a cytosine decavanadate: toward a better understanding
      of chemical and biological properties of decavanadates.
AB  - We have synthesized and crystallized a cytosine-decavanadate compound, Na(3)
      [V(10)O(28)] (C(4)N(3)OH(5))(3)(C(4)N(3)OH(6))(3).10H(2)O, and its crystal
      structure has been determined from a single-crystal X-ray diffraction. A high
      resolution X-ray diffraction experiment at 210 K (in P1 space group phase) was
      carried out. The data were refined using a pseudo-atom multipole model to get the
      electron density and the electrostatic properties of the decavanadate-cytosine
      complex. Static deformation density maps and Atoms in Molecules (AIM) topological
      analysis were used for this purpose. To get insight into the reactivity of the
      decavanadate anion, we have determined the atomic net charges and the molecular
      electrostatic potential. Special attention was paid to the hydrogen bonding
      occurring in the solid state between the decavanadate anion and its environment.
      The comparison of the experimental electronic characteristics of the decavanadate
      anions to those found in literature reveals that this anion is a rigid entity
      conserving its intrinsic properties. This is of particular importance for the
      future investigations of the biological activities of the decavanadate anion.

PMID- 19764782
TI  - Reorientation of thiols during 2D self-assembly: interplay between steric and
      energetic factors.
AB  - Reorientation of thiols during their 2D self-assembly is well established;
      however, little is known about its energetics and the factors that control its
      onset. We have developed a new strategy to determine the critical reorientational
      surface concentration (crsc) of thiols at the substrate/solution interface, which
      makes use of a cathodic stripping protocol. Its application to distinct
      homologous series of alkylthiols shows that the magnitude of the crsc and its
      variation with the molecular size is strongly dependent on the nature of the
      terminal group. Methyl-terminated alkylthiols reorient close to the saturation
      coverage of the lying-down phase, thus following their molecular size trend;
      whereas reorientation of alkylthiols bearing a negatively charged end group
      starts well below the monolayer coverage of the lying-down phase, with its onset
      being almost independent of the molecular size. Hydroxy-terminated alkylthiols
      show an intermediate behavior. A theoretical approach is developed to determine
      the reorientation equilibrium constant from the crsc value. The standard free
      energy of reorientation has been found to vary linearly with the alkyl chain
      length, and to increase upon replacing the terminal methyl group by a negatively
      charged one. A quantitative correlation between the reorientation equilibrium
      constant and the hydrophobicity of the molecule has been established. Overall,
      these findings have allowed us to disentangle the role of steric and energetic
      factors in the onset of the reorientation process of alkylthiols, demonstrating
      that their interplay can be finely tuned by varying either the alkyl chain length
      or the nature of the terminal group.

PMID- 19764783
TI  - Probing electronic properties of molecular engineered zinc oxide nanowires with
      photoelectron spectroscopy.
AB  - ZnO nanowires (NWs) are emerging as key elements for new lasing, photovoltaic and
      sensing applications but elucidation of their fundamental electronic properties
      has been hampered by a dearth of characterization tools capable of probing single
      nanowires. Herein, ZnO NWs were synthesized in solution and integrated into a low
      energy photoelectron spectroscopy system, where quantitative optical measurements
      of the NW work function and Fermi level location within the band gap were
      collected. Next, the NWs were decorated with several dipolar self-assembled
      monolayers (SAMs) and control over the electronic properties is demonstrated,
      yielding a completely tunable hybrid electronic material. Using this new
      metrology approach, a host of other extraordinary interfacial phenomena could be
      explored on nanowires such as spatial dopant profiling or heterostructures.

PMID- 19764784
TI  - Clustering of stimuli on single-walled carbon nanotube bundles enhances cellular
      activation.
AB  - Functionalized single-walled carbon nanotube bundles (f-bSWNT) adsorbed with T
      cell-stimulating antibodies are shown to enhance both the kinetics and magnitude
      of T cell stimulation compared to the same concentration of free antibodies in
      solution. This enhancement is unique to f-bSWNT compared to other artificial
      substrates with high surface area and similar chemistry. We explored the origins
      of this enhanced activity with FRET microscopy and found the preferential
      formation of large antibody stimuli clusters (5 to 6 microm) on the surface of
      functionalized versus untreated nanotubes. This highlights the important aspect
      that antigen clusters can be formed on f-bSWNT, impacting the potency of the T
      cell stimulus. Clustering of T cell antigens on artificial substrates impacts the
      avidity of interaction with cells facilitating rapid stimulation dynamics and an
      overall greater magnitude of response. These findings support the use of
      chemically treated nanotube bundles as an efficient substrate for the
      presentation of antigens and point to their potential in clinical applications
      involving artificial antigen-presentation for ex vivo T cell expansion in
      adoptive immunotherapy.

PMID- 19764785
TI  - Selection of single chain fragment variables with direct coating of aflatoxin B1
      to enzyme-linked immunosorbent assay plates.
AB  - Most selections of antihapten recombinant antibodies from antibody libraries were
      against hapten-carrier conjugates, which are different from free haptens in
      antigen specificity and often mislead the screening due to immunodominant
      epitopes in carriers. In the present study, aflatoxin B(1) (AFB(1)) was directly
      coated to enzyme-linked immunosorbent assay (ELISA) plates and anti-AFB(1) single
      chain fragment variables (scFvs) were selected with the AFB(1)-coated plates.
      Compared to the selection against AFB(1)-bovine serum albumin conjugate (31
      positives out of 46 random clones), the isolated scFvs against AFB(1) (44
      positives out of 46 random clones) showed higher specificities for AFB(1). The
      clone H4 with K(D) of 9.8 x 10(-11) M to AFB(1)-BSA and K(D) of 1.2 x 10(-12) to
      AFB1 was sequenced. In addition, polymerase chain reaction-denaturing gradient
      gel electrophoresis (PCR-DGGE) was applied to describe the biopanning for the
      first time. Our research presents a quick and robust selection technique for
      antihapten recombinant antibody from large naive libraries.

PMID- 19764786
TI  - Structure-brain exposure relationships in rat and human using a novel data set of
      unbound drug concentrations in brain interstitial and cerebrospinal fluids.
AB  - New experimental methodologies were applied to measure the unbound brain-to
      plasma concentration ratio (K(p,uu,brain)) and the unbound CSF-to-plasma
      concentration ratio (K(p,uu,CSF)) in rats for 43 structurally diverse drugs. The
      relationship between chemical structure and K(p,uu,brain) was dominated by
      hydrogen bonding. Contrary to popular understanding based on the total brain-to
      plasma concentration ratio (logBB), lipophilicity was not a determinant of
      unbound brain exposure. Although changing the number of hydrogen bond acceptors
      is a useful design strategy for optimizing K(p,uu,brain), future improvement of
      in silico prediction models is dependent on the accommodation of active drug
      transport. The structure-brain exposure relationships found in the rat also hold
      for humans, since the rank order of the drugs was similar for human and rat
      K(p,uu,CSF). This cross-species comparison was supported by K(p,uu,CSF) being
      within 3-fold of K(p,uu,brain) in the rat for 33 of 39 drugs. It was, however,
      also observed that K(p,uu,CSF) overpredicts K(p,uu,brain) for highly effluxed
      drugs, indicating lower efflux capacity of the blood-cerebrospinal fluid barrier
      compared to the blood-brain barrier.

PMID- 19764787
TI  - Reactions of the unsaturated complex [Mo(2)(eta(5)-C(5)H(5))(2)(mu
      PEt(2))(2)(CO)(2)] with [Au(PR(3))](+) cations: kinetic preference of the Mo-P
      bonds as the site of attack of the gold(I) electrophile.
AB  - The title complex reacts with [Au(PR(3))](+) cations (PF(6)(-) salts, R = p-tol,
      Me) in dichloromethane solutions to give first the corresponding agostic-like
      products [AuMo(2)Cp(2)(mu-PEt(2))(mu(3)-PEt(2))(CO)(2)(PR(3))]PF(6), which then
      partially rearrange to reach an equilibrium with the hydride-like isomers
      [AuMo(2)Cp(2)(mu-PEt(2))(2)(CO)(2)(PR(3))]PF(6), the latter being characterized
      through an X-ray study (R = p-tol, Mo-Mo = 2.8244(2) A). These unsaturated
      complexes react smoothly with CO (1 atm) to give the corresponding electron
      precise derivatives [AuMo(2)Cp(2)(mu-PEt(2))(2)(CO)(3)(PR(3))](+) (Mo-Mo =
      3.0438(6) A when R = Me), this implying the rearrangement of the mu(3)-PEt(2)
      ligand to a more common mu(2)-coordination mode. Density functional theory (DFT)
      calculations on the dimolybdenum complexes [Mo(2)Cp(2)(mu-PR(2))(2)(CO)(2)] (R =
      Cy, Et) reveal the presence of a framework M-P bonding orbital high in energy and
      with the right shape to act as a donor to H(+) and [Au(PR(3))](+) cations, thus
      explaining the formation of agostic and agostic-like products respectively in
      these reactions. The unusually high energy of this donor orbital can be related
      to the close approach of the metal centers in these unsaturated molecules. The
      carbyne complex [Mo(2)Cp(2)(mu-COMe)(mu-PCy(2))(CO)(2)] reacts with [Au{P(p
      tol)(3)}](+) to give the tricarbonyl [AuMo(2)Cp(2)(mu-COMe)(mu-PCy(2))(CO)(3){P(p
      tol)(3)}](+) (Mo-Mo = 2.986(1) A), a process most likely initiated by the binding
      of the gold cation to one of the Mo-P bonds in the carbyne complex.

PMID- 19764788
TI  - Transformation of reactive isochromenylium intermediates to stable salts and
      their cascade reactions with olefins.
AB  - Transformation of reactive isochromenylium intermediates to the corresponding
      storable and stable reagents has been achieved, and a number of isochromenylium
      tetrafluoroborates (ICTBs, 1) have been conveniently prepared and characterized.
      Direct metal-free treatment of isochromenylium tetrafluoroborate 1a with olefins
      afforded a variety of polycyclic frameworks 4 via mild cascade reactions.
      Starting from the prefunctionalized o-alkynylbenzaldehydes, a one-pot metal-free
      procedure of intramolecular cascade annulation to 2,3-dihydrophenanthren-4(1H)
      one derivatives was also developed.

PMID- 19764789
TI  - Highly enantioselective Friedel-Crafts reaction of thiophenes with glyoxylates:
      formal synthesis of duloxetine.
AB  - An efficient Friedel-Crafts reaction of a series of 2-substituted thiophenes with
      alkyl glyoxylates has been developed using a catalytic amount of an easy
      accessible 6,6'-dibromo-BINOL/Ti(IV) complex. A variety of hydroxy(thiophene-2
      yl)acetates can be synthesized in high enantioselectivites (92-98% ee) and good
      yields. This is the first report on the efficient asymmetric F-C reaction of
      thiophenes with alkyl glyoxylates. Starting from simple thiophene and n-butyl
      glyoxylate, we demonstrated the formal synthesis of duloxetine.

PMID- 19764790
TI  - Spin maximization from S = 11 to S = 16 in Mn(7) disk-like clusters: spin
      frustration effects and their computational rationalization.
AB  - The use has been explored in Mn cluster chemistry of N(3)(-) or Cl(-) in
      combination with N-methyldiethanolamine (mdaH(2)) or triethanolamine (teaH(3)).
      The reactions of Mn(ClO(4))(2).6H(2)O, NEt(3), NaN(3), and either mdaH(2) or
      teaH(3) (1:2:1:2) in DMF/MeOH afford {[Na(MeOH)(3)][Mn(7)(N(3))(6)(mda)(6)]}(n)
      (1) and {Na[Mn(7)(N(3))(6)(teaH)(6)]}(n) (2), respectively, whereas the 2:1:1
      reaction of MnCl(2).4H(2)O, mdaH(2), and NEt(3) in MeCN gives
      (NHEt(3))[Mn(7)Cl(6)(mda)(6)] (3). Similar reactions using NBu(n)(4)N(3) in place
      of NaN(3) gave (NHEt(3))[Mn(7)(N(3))(6)(mda)(6)] (4) and
      (NHEt(3))[Mn(7)(N(3))(6)(teaH)(6)] (5). The Mn(7) anions consist of a Mn(6)
      hexagon of alternating Mn(II) and Mn(III) ions surrounding a central Mn(II) ion.
      The remaining ligation is by six bridging and chelating mda(2-) or teaH(2-)
      groups, and either six terminal N(3)(-) (1, 2, 4, 5) or Cl(-) (3) ions. Each
      bridging mda(2-) or teaH(2-) ligand contains both mu- and mu(3)-O atoms,
      resulting in a similar, near-planar [Mn(7)(mu(3)-OR)(6)(mu-OR)(6)](5+) core for
      all three complexes. The Mn(7) anions of 1 and 2 are connected via Na(+) cations
      to yield one-dimensional zigzag chains and three-dimensional windmill-like
      "hexagons-of-hexagons", respectively. In contrast, the Mn(7) anion of 3 forms a
      strong hydrogen-bond between the NHEt(3)(+) cation and a terminal Cl(-) ion
      giving a discrete ion-pair. Variable-temperature, solid-state direct current (dc)
      and alternating current (ac) magnetization studies were carried out in the 5.0
      300 K range. Fits of dc magnetization versus field (H) and temperature (T) data
      by matrix diagonalization gave S = 11, g = 1.95, D = -0.15 cm(-1) for 1, S = 16,
      g = 1.95, D = -0.02 cm(-1) for 2, and S = 11, g = 1.92, D = -0.13 cm(-1) for 3 (D
      is the axial zero-field splitting parameter). Complexes 4 and 5 were also found
      to possess S = 11 and S = 16 ground states, respectively. The different ground
      states of 1 and 2 were rationalized on the basis of the sign and magnitude of the
      various Mn(2) exchange parameters obtained from density functional theory (DFT)
      calculations. This analysis confirmed the presence of spin frustration effects,
      with the ground states being determined by the relative magnitude of the two
      weakest interactions. The combined results demonstrate the usefulness of N-based
      dipodal and tripodal alkoxide-based chelates as a route to structurally and
      magnetically interesting Mn clusters.

PMID- 19764792
TI  - Comment on "Excited states of DNA base pairs using long-range corrected time
      dependent density functional theory".

PMID- 19764793
TI  - Identification of biphenyl-based hybrid molecules able to decrease the
      intracellular level of Bcl-2 protein in Bcl-2 overexpressing leukemia cells.
AB  - With the aim of enhancing the structural complexity and diversity of an existing
      collection of bi- and terphenyl compounds, we synthesized hybrid molecules
      comprising of spirocyclic ketones (a complexity-bearing core) and bi/terphenyls
      (privileged fragments). Compounds 1, 3, 4, and 6 showed well-defined activity on
      apoptosis and differentiation, making them potential leads for development as new
      anticancer agents and chemical probes to study signaling networks in neoplastic
      cells.

PMID- 19764794
TI  - Selective inhibitors of the mutant B-Raf pathway: discovery of a potent and
      orally bioavailable aminoisoquinoline.
AB  - The discovery and optimization of a novel series of aminoisoquinolines as potent,
      selective, and efficacious inhibitors of the mutant B-Raf pathway is presented.
      The N-linked pyridylpyrimidine benzamide 2 was identified as a potent, modestly
      selective inhibitor of the B-Raf enzyme. Replacement of the benzamide with an
      aminoisoquinoline core significantly improved kinase selectivity and imparted
      favorable pharmacokinetic properties, leading to the identification of 1 as a
      potent antitumor agent in xenograft models.

PMID- 19764795
TI  - Development of Langmuir-Schaeffer cellulose nanocrystal monolayers and their
      interfacial behaviors.
AB  - Model cellulose surfaces based on cellulose nanocrystals (CNs) were prepared by
      the Langmuir-Schaeffer technique. Cellulose nanocrystals were obtained by acid
      hydrolysis of different natural fibers, producing rodlike nanoparticles with
      differences in charge density, aspect ratio, and crystallinity.
      Dioctadecyldimethylammonium bromide (DODA-Br) cationic surfactant was used to
      create CN-DODA complexes that allowed transfer of the CNs from the air/liquid
      interface in an aqueous suspension to hydrophobic solid substrates. Langmuir
      Schaeffer horizontal deposition at various surface pressures was employed to
      carry out such particle transfer that resulted in CN monolayers coating the
      substrate. The morphology and chemical composition of the CN films were
      characterized by using atomic force microscopy (AFM) and X-ray photoelectron
      spectroscopy (XPS). Also, their swelling behavior and stability after treatment
      with aqueous and alkaline solutions were studied using quartz crystal
      microgravimetry (QCM). Overall, it is concluded that the Langmuir-Schaeffer
      method can be used to produce single coating layers of CNs that were shown to be
      smooth, stable, and strongly attached to the solid support. The packing density
      of the films was controlled by selecting the right combination of surface
      pressure during transfer to the solid substrate and the amount of CNs available
      relative to the cationic charges at the interface.

PMID- 19764796
TI  - A terminal molybdenum arsenide complex synthesized from yellow arsenic.
AB  - A terminal molybdenum arsenide complex is synthesized in one step from the
      reactive As(4) molecule. The properties of this complex with its arsenic atom
      ligand are discussed in relation to the analogous nitride and phosphide
      complexes.

PMID- 19764797
TI  - Hybrid lanthanide nanoparticles with paramagnetic shell coated on upconversion
      fluorescent nanocrystals.
AB  - Nanoparticles comprising of fluorescent probes and MRI contrast agents are highly
      desirable for biomedical applications due to their ability to be detected at
      different modes, optically and magnetically. However, most fluorescent probes in
      such nanoparticles synthesized so far are down-conversion phosphors such as
      organic dyes and quantum dots, which are known to display many intrinsic
      limitations. Here, we report a core-shell hybrid lanthanide nanoparticle
      consisting of an upconverting lanthanide nanocrystal core and a paramagnetic
      lanthanide complex shell. These nanoparticles are uniform in size, stable in
      water, and show both high MR relaxivities and upconversion fluorescence, which
      may have the potential to serve as a versatile imaging tool for smart detection
      or diagnosis in future biomedical engineering.

PMID- 19764798
TI  - Processing of graphene for electrochemical application: noncovalently
      functionalize graphene sheets with water-soluble electroactive methylene green.
AB  - To explore graphene applications in various fields, the processability of
      graphene becomes one of the important key issues, particularly with the
      increasing availability of synthetic graphene approaches, because the direct
      dispersion of hydrophobic graphene in water is prone to forming agglomerates
      irreversibly. Here, a facile method is proposed to increase the dispersity of
      graphene through noncovalent functionalization graphene with a water-soluble
      aromatic electroactive dye, methylene green (MG), during chemical reduction of
      graphene oxide (GO) with hydrazine. Atomic force microscopic and UV-vis
      spectrophotometric results demonstrate that chemically reduced graphene (CRG)
      functionalized with MG (CRG-MG) is well-dispersed into water through the coulomb
      repulsion between MG-adsorbed CRG sheets. The electrochemical properties of the
      formed CRG-MG are investigated, and the results demonstrate that CRG-MG confined
      onto a glassy carbon (GC) electrode has lower charge-transfer resistance and
      better electrocatalytic activity toward the oxidation of NADH, in relation to
      pristine CRG (i.e., without MG functionalization). This method not only offers a
      facile approach to dispersing graphene in water but also is envisaged to be
      useful for investigations on graphene-based electrochemistry.

PMID- 19764799
TI  - Chemical synthesis of a hyaluronic acid decasaccharide.
AB  - The chemical synthesis of a hyaluronic acid decasaccharide using the
      preactivation-based chemoselective glycosylation strategy is described. Assembly
      of large oligosaccharides is generally challenging due to the increased
      difficulties in both glycosylation and deprotection. Indeed, the same building
      blocks previously employed for hyaluronic acid hexasaccharide syntheses failed to
      yield the desired decasaccharide. After extensive experimentation, the
      decasaccharide backbone was successfully constructed with an overall yield of 37%
      from disaccharide building blocks. The trichloroacetyl group was used as the
      nitrogen protective group for the glucosamine units, and the addition of TMSOTf
      was found to be crucial to suppress the formation of trichloromethyl oxazoline
      side product and enable high glycosylation yield. For deprotections, the
      combination of a mild basic condition and the monitoring methodology using (1)H
      NMR allowed the removal of all base-labile protective groups, which facilitated
      the generation of the fully deprotected HA decasaccharide.

PMID- 19764800
TI  - Heterogeneous electron transfer of a two-centered heme protein: redox and
      electrocatalytic properties of surface-immobilized cytochrome C(4).
AB  - The recombinant diheme cytochrome c(4) from the psycrophilic bacterium
      Pseudoalteromonas haloplanktis TAC 125 and its Met64Ala and Met164Ala variants,
      which feature a hydroxide ion axially bound to the heme iron at the N- and C
      terminal domains, respectively, were found to exchange electrons efficiently with
      a gold electrode coated with a SAM of 11-mercapto-1-undecanoic acid. The mutation
      induced removal of the redox equivalence of the two heme groups and changes in
      the net charge of the protein lobes yield two-centered protein systems with
      unprecedented properties in the electrode-immobilized state. The heterogeneous
      and intraheme electron transfer processes were characterized for these species in
      which the high- and low-potential heme groups are swapped over in the bilobal
      protein framework and experience a constrained (M64A) and unconstrained (M164A)
      orientation toward the electrode. The reduction thermodynamics for the native and
      mutated hemes were measured for the first time for a diheme cytochrome c. In the
      diffusing regime, they reproduce closely those for the corresponding centers in
      single-heme class-I cytochromes c, despite the low sequence identity. Larger
      differences are observed in the thermodynamics of the immobilized species and in
      the heterogeneous electron transfer rate constants. T-dependent kinetic
      measurements show that the proteins are positioned approximately 7 A from the
      HOOC-terminated SAM-coated electrode. Protein-electrode orientation and efficient
      intraheme ET enable the His,OH(-)-ligated heme A of the immobilized Met64Ala
      variant to carry out the reductive electrocatalysis of molecular oxygen. This
      system therefore constitutes a novel two-centered heme-based biocatalytic
      interface to be exploited for "third-generation" amperometric biosensing.

PMID- 19764801
TI  - Effects of restricted rotations and dynamic averaging on the calculated isotropic
      hyperfine coupling constants of the bis-dimethyl and bis-Di(trifluoromethyl)
      nitroxide radicals.
AB  - The rotational effects of the CH(3) and CF(3) groups on the electronic structure
      and nuclear hyperfine coupling constants (HFCCs) in dimethylnitroxide (DMNO*) and
      ditrifluoro-methynitroxide (TFMNO*) are investigated using the UB1LYP hybrid
      density functional method. The CH(3) and CF(3) HFCCs of both radicals are found
      to obey the McConnell relation during rotation. The two CH(3) groups of the DMNO*
      do not gear with each other, but the rotation of the first CH(3) group induces
      only a small rocking effect ( approximately 7 degrees ) in the second group.
      However, in TFMNO*, the fluorine atoms from different CF(3) groups are close
      enough so that the steric repulsion between them causes them to act as two
      interlocked gears, where one drives the other. Therefore, both CF(3) groups
      undergo full rotation. To the best of our knowledge, this is only the second
      example of "gearing" to be studied. Stabilization due to hyperconjugation is also
      a major factor that affects the magnitudes of the HFCCs of the CF(3) groups
      during rotational averaging. Stable configurations at specific CF(3) group
      orientations have a large overlap with the NO pi-electron cloud because the lobes
      of the hybridized p(sigma)(F(2)), p(sigma)(F(3)), p(sigma)(F(5)), and
      p(sigma)(F(6)) orbitals along the F-C bonds have cylindrical symmetry and are of
      the correct phases for hyperconjugation to occur. The calculated TFMNO* C(1)-N
      and C(2)-N bond orders range from 0.91 to 0.95 as the CF(3) groups are rotated.
      Therefore, the C-N bonds are essentially single bonds. This, in conjunction with
      the low rotational energy barrier of approximately 50 cm(-1), explains why the
      EPR intensities of the (19)F hyperfine splittings, in the range of 163-297 K, are
      characteristic of six equivalent rapidly rotating fluorine atoms. The TFMNO* out
      of-plane NO vibrations induce additional s character at the (14)N nucleus. This
      increases the magnitude of the (14)N HFCC and decreases the (19)F HFCCs. As the
      temperature increases and because of mixing of the first excited out-of-plane
      vibrational state, the NO vibrational amplitudes also increase. This leads to an
      increased (14)N HFCC and decreased (19)F HFCCs, which is in agreement with
      experiment.

PMID- 19764802
TI  - Collisional quenching of excited electronic species and the Parmenter et al.
      correlation.
AB  - The model of collision-induced deactivation of excited species proposed by
      Parmenter and co-workers has been examined in its application to the collisional
      quenching of PH(2)(A(2)A(1)). The correlation between the quenching efficiency
      and the molecular properties of the quenchers is seen to be closely obeyed only
      by rare gases and two molecules, H(2) and CH(4). The other molecular quenchers,
      conversely, show only a very loose trend of variation with the quantity epsilon(M
      M), well depth of the potential between two molecules of the quencher M, which
      constitutes the basis for application of the Parmenter et al. model. This
      apparent limited validity of the Parmenter et al. correlation has been ascribed
      to the fact that the combining rule applied to the well depth epsilon(PH(2)*-M)
      of the collision complex PH(2)*-M to express this quantity as (epsilon(PH(2)*
      PH(2)*))(1/2)(epsilon(M-M))(1/2) is applicable only to rare gases and not to most
      of the other quenchers. A procedure to find the characteristics of rare gas-like
      molecules with quenching efficiencies equal to those of the real quenchers has
      been proposed. A plot of the quenching data vs (epsilon(Mh-Mh)/k)(1/2) of these
      hypothetical molecules M(h) with the exception of NO, PH(3), NH(3), and H(2)S
      shows data points lying on the rare gas line. This indicates that the Parmenter
      et al. correlation is again verified and that the quenching mechanism of the
      corresponding real quenchers is the same as that of the rare gases. For NO,
      PH(3), NH(3), and H(2)S it has been demonstrated that chemical reactions should
      play an important role in the removal of PH(2)(A(2)A(1)), and the relative parts
      of physical and chemical quenchings have been evaluated. It has also been
      possible to determine the otherwise inaccesible quantity epsilon(PH(2)*-M), i.e.,
      the well depth of the collision complexes, present in the original equation of
      the Parmenter et al. model. By plotting the quenching data vs epsilon(PH(2)*
      M)/k, it can be seen again that the Parmenter et al. model is followed by all the
      quenchers treated, except the above-mentioned molecules.

PMID- 19764803
TI  - Yamaguchi-type lactonization as a key step in the synthesis of marine
      metabolites: (+)-luffalactone.
AB  - A Yamaguchi-type cyclization of 5 and subsequent photochemical oxidation of the
      furanic ring are the key steps in the first synthesis of the marine metabolite
      (+)-luffalactone 4 and its epimer at C-16, 16-epi-luffalactone, 27. With this
      work, we have successfully established the absolute configuration of the natural
      product. The key intermediate 5 was obtained from the easily accessible diacetate
      6a/6b.

PMID- 19764804
TI  - Exploring 1,2-hydrogen shift in silicon nanoparticles: reaction kinetics from
      quantum chemical calculations and derivation of transition state group additivity
      database.
AB  - Accurate rate coefficients for 35 1,2-hydrogen shift reactions for hydrides
      containing up to 10 silicon atoms have been calculated using G3//B3LYP. The
      overall reactions exhibit two distinct barriers. Overcoming the first barrier
      results in the formation of a hydrogen-bridged intermediate species from a
      substituted silylene and is characterized by a low activation energy. Passing
      over the second barrier converts this stable intermediate into the double-bonded
      silene. Values for the single event Arrhenius pre-exponential factor, A, and the
      activation energy, E(a), were calculated from the G3//B3LYP rate coefficients,
      and a group additivity scheme was developed to predict A and E(a). The values
      predicted by group additivity are more accurate than structure/reactivity
      relationships currently used in the literature, which rely on a representative A
      value and the Evans-Polanyi correlation to predict E(a). The structural factors
      that have the most pronounced effect on A and E(a) were considered, and the
      presence of rings was shown to influence these values strongly.

PMID- 19764805
TI  - Catalytic and thermal 1,2-rearrangement of (alpha-mercaptobenzyl)trimethylsilane.
AB  - The mechanisms of catalytic and thermal 1,2-rearrangement of (alpha
      mercaptobenzyl)trimethylsilane were studied by using density functional theory
      (DFT) at the MP2/6-31+G(d,p)//B3LYP/6-31G(d) levels. The results show that (alpha
      mercaptobenzyl)trimethylsilane rearranges to (benzylthio)trimethylsilane through
      a trimethylsilyl group migration from C to S atom via a transition state of
      pentacoordinate Si atom with or without radical initiators. The low reaction
      activation energy (15.1 kcal/mol) is responsible for the fast rearrangement in
      the presence of radical initiators. Both radical and nonradical thermal
      rearrangement mechanisms were suggested, and the radical mechanism dominates
      through its self-catalyzing. These results are consistent with the experiment
      results. The activation energy (DeltaH(act) = 15.1 kcal/mol) for the rate
      determining step within the self-catalytic cycle is low enough to make
      (trimethylsilylbenzyl)thiyl radical be a reasonable catalyst for the thermal
      rearrangement. The catalytic and thermal 1,2-rearrangement mechanisms of (alpha
      mercaptobenzyl)trimethylsilane, especially the self-catalytic radical mechanism,
      were revealed for the first time. The comparison of the rearrangement mechanisms
      between (alpha-mercaptobenzyl)trimethylsilane and silylmethanethiol discloses the
      factors in determining the reaction mechanism of such kinds of mercaptoalkyl
      functionalized organosilanes. The phenyl group is found to be favorable for the
      radical rearrangement, thus making (alpha-mercaptobenzyl)trimethylsilane
      instable.

PMID- 19764806
TI  - Proteomic identification of caldesmon as a physiological substrate of proprotein
      convertase 6 in human uterine decidual cells essential for pregnancy
      establishment.
AB  - Proprotein convertase 5/6 (PC6), a member of the proprotein convertase (PC)
      family, is a critical regulator in the uterus for embryo implantation. In
      particular, PC6 is essential for the differentiation of uterine stromal
      fibroblasts into decidual cells (decidualization). Knockdown of PC6 in the mouse
      uterus leads to complete failure of decidualization and implantation. It has been
      envisaged that PC6 functions by proteolytically activating a number of important
      growth factors and other precursor proteins. However, to date, the precise
      mechanism of PC6 action in the uterus, particularly during decidualization, is
      unknown. In this study, we aimed to investigate the mechanisms of PC6 action in
      decidualization by identifying its physiological substrates using a proteomic
      approach. Primary human endometrial stromal cells were decidualized and treated
      with or without recombinant human PC6 (rhPC6). The proteins cleaved by rhPC6 were
      identified by 2-dimensional fluorescent differential gel electrophoresis. The
      candidate proteins were validated as PC6 substrates by a number of approaches,
      including determining their coexpression with PC6 in vivo in decidual cells in
      the human uterus. A total of 18 protein spots were significantly altered by rhPC6
      treatment, 8 of which were assigned clear identities by mass spectrometry. One of
      these was confirmed to be caldesmon, a key protein involved in organizing the
      actin microfilaments and regulating cytoskeletal structure. This study
      demonstrates a novel approach to identify PC-regulated proteins of physiological
      relevance, and provides important insight into the mechanism by which PC6
      regulates decidualization.

PMID- 19764807
TI  - Identification of N-glycan serum markers associated with hepatocellular carcinoma
      from mass spectrometry data.
AB  - Glycocylation represents the most complex and widespread post-translational
      modifications in human proteins. The variation of glycosylation is closely
      related to oncogenic transformation. Therefore, profiling of glycans detached
      from proteins is a promising strategy to identify biomarkers for cancer
      detection. This study identified candidate glycan biomarkers associated with
      hepatocellular carcinoma by mass spectrometry. Specifically, mass spectrometry
      data were analyzed with a peak selection procedure which incorporates multiple
      random sampling strategies with recursive feature selection based on support
      vector machines. Ten peak sets were obtained from different combinations of
      samples. Seven peaks were shared by each of the 10 peaksets, in which 7-12 peaks
      were selected, indicating 58-100% of peaks were shared by the 10 peaksets.
      Support vector machines and hierarchical clustering method were used to evaluate
      the performance of the peaksets. The predictive performance of the seven peaks
      was further evaluated by using 19 newly generated MALDI-TOF spectra. Glycan
      structures for four glycans of the seven peaks were determined. Literature search
      indicated that the structures of the four glycans could be found in some cancer
      related glycoproteins. The method of this study is significant in deriving
      consistent, accurate, and biological significant glycan marker candidates for
      hepatocellular carcinoma diagnosis.

PMID- 19764808
TI  - Modified spectral count index (mSCI) for estimation of protein abundance by
      protein relative identification possibility (RIPpro): a new proteomic
      technological parameter.
AB  - Peptides Count (SC) was widely used for protein abundance estimation in
      proteomics. On the basis of that, Mann and co-workers corrected the SC by
      dividing spectrum counts by the number of observable peptides per protein and
      named it PAI. Here we present modified spectral count index (mSCI) for protein
      abundance estimation, which was defined as the number of observed peptides
      divided by protein relative identification possibility (RIPpro). RIPpro was
      derived from 6788 mRNA and protein expression data (collected from human liver
      samples) and related to proteins' three physical and chemical properties
      (MW/pI/Hp). For 46 proteins in mouse neuro2a cells, mSCI shows a linear
      relationship with the actual protein concentration, similar or better than PAI
      abundance. Also, multiple linear regressions were performed to quantitative
      assess several factors' impact on the mRNA/protein abundance correlation. Our
      results shown that the primary factor affecting protein levels was mRNA abundance
      (32-37%), followed by variability in protein measurement, MW and protein turnover
      (7-12%,7-9% and 2-3%, respectively). Interestingly, we found that the concordance
      between mRNA transcripts and protein expression was not consistent among all
      protein functional categories. This correlation was lower for signaling proteins
      as compared to metabolism genes. It was determined that RIPpro was the primary
      factor affecting signaling protein abundance (23% on average), followed by mRNA
      abundance (17%). In contrast, only 5% (on average) of the variability of
      metabolic protein abundance was explained by RIPpro, much lower than mRNA
      abundance (40%). These results provide the impetus for further investigation of
      the biological significance of mechanisms regulating the mRNA/protein abundance
      correlation and provide additional insight into the relative importance of the
      technological parameter (RIPpro) in mRNA/protein correlation research.

PMID- 19764809
TI  - Identifying protein complexes using hybrid properties.
AB  - Protein complexes, integrating multiple gene products, perform all sorts of
      fundamental biological functions in cells. Much effort has been put into
      identifying protein complexes using computational approaches. A vast majority
      attempt to research densely connected regions in protein-protein interaction
      (PPI) network/graph. In this research, we try an alterative approach to analyze
      protein complexes using hybrid features and present a method to determine whether
      multiple (more than two) proteins from yeast can form a protein complex. The data
      set consists of 493 positive protein complexes and 9878 negative protein
      complexes. Every complex is represented by graph features, where proteins in the
      complex form a graph (web) of interactions, and features derived from biological
      properties including protein length, biochemical properties and physicochemical
      properties. These features are filtered and optimized by Minimum Redundancy
      Maximum Relevance method, Incremental Feature Selection and Forward Feature
      Selection, established through a prediction/identification model called Nearest
      Neighbor Algorithm. Jackknife cross-validation test is employed to evaluate the
      identification accuracy. As a result, the highest accuracy for the identification
      of the real protein complexes using filtered features is 69.17%, and feature
      analysis shows that, among the adopted features, graph features play the main
      roles in the determination of protein complexes.

PMID- 19764810
TI  - Quantitative analysis of age specific variation in the abundance of human female
      parotid salivary proteins.
AB  - Human saliva is a protein-rich, easily accessible source of potential local and
      systemic biomarkers to monitor changes that occur under pathological conditions;
      however, little is known about the changes in abundance associated with normal
      aging. In this study, we performed a comprehensive proteomic profiling of pooled
      saliva collected from the parotid glands of healthy female subjects, divided into
      two age groups 1 and 2 (20-30 and 55-65 years old, respectively). Hydrophobic
      charge interaction chromatography was used to separate high- from low-abundance
      proteins prior to characterization of the parotid saliva using multidimensional
      protein identification technology (MudPIT). Collectively, 532 proteins were
      identified in the two age groups. Of these proteins, 266 were identified
      exclusively in one age group, while 266 proteins were common to both groups. The
      majority of the proteins identified in the two age groups belonged to the defense
      and immune response category. Of note, several defense related proteins (e.g.,
      lysozyme, lactoferrin and histatin-1) were significantly more abundant in group 2
      as determined by G-test. Selected representative mass spectrometric findings were
      validated by Western blot analysis. Our study reports the first quantitative
      analysis of differentially regulated proteins in ductal saliva collected from
      young and older female subjects. This study supports the use of high-throughput
      proteomics as a robust discovery tool. Such results provide a foundation for
      future studies to identify specific salivary proteins which may be linked to age
      related diseases specific to women.

PMID- 19764811
TI  - In vivo phosphoproteome of human skeletal muscle revealed by phosphopeptide
      enrichment and HPLC-ESI-MS/MS.
AB  - Protein phosphorylation plays an essential role in signal transduction pathways
      that regulate substrate and energy metabolism, contractile function, and muscle
      mass in human skeletal muscle. Abnormal phosphorylation of signaling enzymes has
      been identified in insulin-resistant muscle using phosphoepitope-specific
      antibodies, but its role in other skeletal muscle disorders remains largely
      unknown. This may be in part due to insufficient knowledge of relevant targets.
      Here, we therefore present the first large-scale in vivo phosphoproteomic study
      of human skeletal muscle from 3 lean, healthy volunteers. Trypsin digestion of 3
      5 mg human skeletal muscle protein was followed by phosphopeptide enrichment
      using SCX and TiO(2). The resulting phosphopeptides were analyzed by HPLC-ESI
      MS/MS. Using this unbiased approach, we identified 306 distinct in vivo
      phosphorylation sites in 127 proteins, including 240 phosphoserines, 53
      phosphothreonines, and 13 phosphotyrosines in at least 2 out of 3 subjects. In
      addition, 61 ambiguous phosphorylation sites were identified in at least 2 out of
      3 subjects. The majority of phosphoproteins detected are involved in sarcomeric
      function, excitation-contraction coupling (the Ca(2+)-cycle), glycolysis, and
      glycogen metabolism. Of particular interest, we identified multiple novel
      phosphorylation sites on several sarcomeric Z-disk proteins known to be involved
      in signaling and muscle disorders. These results provide numerous new targets for
      the investigation of human skeletal muscle phosphoproteins in health and disease
      and demonstrate feasibility of phosphoproteomics research of human skeletal
      muscle in vivo.

PMID- 19764812
TI  - One-pot shotgun quantitative mass spectrometry characterization of histones.
AB  - Despite increasing applications of mass spectrometry (MS) to characterize post
      translational modifications (PTMs) on histone proteins, most existing protocols
      are not properly suited to robustly measure them in a high-throughput
      quantitative manner. In this work, we expand on current protocols and describe
      improved methods for quantitative Bottom Up characterization of histones and
      their PTMs with comparable sensitivity but much higher throughput than standard
      MS approaches. This is accomplished by first bypassing off-line fractionation of
      histone proteins and working directly with total histones from a typical nuclei
      acid extraction. Next, using a chemical derivatization procedure that is combined
      with stable-isotope labeling in a two-step process, we can quantitatively compare
      samples using nanoLC-MS/MS. We show that our method can successfully detect 17
      combined H2A/H2B variants and over 25 combined histone H3 and H4 PTMs in a single
      MS experiment. We test our method by quantifying differentially expressed histone
      PTMs from wild-type yeast and a methyltransferase knockout strain. This improved
      methodology establishes that time and sample consuming off-line HPLC or SDS-PAGE
      purification of individual histone variants prior to MS interrogation as commonly
      performed is not strictly required. Our protocol significantly streamlines the
      analysis of histone PTMs and will allow for studies of differentially expressed
      PTMs between multiple samples during biologically relevant processes in a rapid
      and quantitative fashion.

PMID- 19764813
TI  - Dramatic differences in organophosphorus hydrolase activity between human and
      chimeric recombinant mammalian paraoxonase-1 enzymes.
AB  - Human serum paraoxonase-1 (HuPON1) has the capacity to hydrolyze aryl esters,
      lactones, oxidized phospholipids, and organophosphorus (OP) compounds. HuPON1 and
      bacterially expressed chimeric recombinant PON1s (G2E6 and G3C9) differ by
      multiple amino acids, none of which are in the putative enzyme active site. To
      address the importance of these amino acid differences, the abilities of HuPON1,
      G2E6, G3C9, and several variants to hydrolyze phenyl acetate, paraoxon, and V
      type OP nerve agents were examined. HuPON1 and G2E6 have a 10-fold greater
      catalytic efficiency toward phenyl acetate than G3C9. In contrast, bacterial
      PON1s are better able to promote hydrolysis of paraoxon, whereas HuPON1 is
      considerably better at catalyzing the hydrolysis of nerve agents VX and VR. These
      studies demonstrate that mutations distant from the active site of PON1 have
      large and unpredictable effects on the substrate specificities and possibly the
      hydrolytic mechanisms of HuPON1, G2E6, and G3C9. The replacement of residue H115
      in the putative active site with tryptophan (H115W) has highly disparate effects
      on HuPON1 and G2E6. In HuPON1, variant H115W loses the ability to hydrolyze VR
      but has improved activity toward paraoxon and VX. The H115W variant of G2E6 has
      paraoxonase activity similar to that of wild-type G2E6, modest activity with
      phenyl acetate and VR, and enhanced VX hydrolysis. VR inhibits H115W HuPON1
      competitively when paraoxon is the substrate and noncompetitively when VX is the
      substrate. We have identified the first variant of HuPON1, H115W, that displays
      significantly enhanced catalytic activity against an authentic V-type nerve
      agent.

PMID- 19764814
TI  - Synergistic regulation and ligand-induced conformational changes of tryptophan
      synthase.
AB  - Conformational changes of enzyme complexes are often related to regulating and
      creating an optimal environment for efficient chemistry. We investigated the
      synergistic regulation of the tryptophan synthase (TRPS) complex, studied for
      decades as a model of allosteric regulation and substrate channeling within
      protein complexes. TRPS is a bifunctional tetrameric alphabetabetaalpha enzyme
      complex that exhibits cooperative motions of the alpha- and beta-subunits by
      tightly controlled allosteric interactions. We have delineated the atomically
      detailed dynamics and conformational changes of TRPS in the absence and presence
      of substrates using molecular dynamics simulations. The computed energy and
      entropy associated with the protein motions also offer mechanistic insights into
      the conformational fluctuations and the ligand binding mechanism. The flexible
      alpha-L6 loop samples both open and partially closed conformations in the ligand
      free state but shifts to fully closed conformations when its substrates are
      present. The fully closed conformations are induced by favorable protein-ligand
      interactions but are partly compensated by configurational entropy loss.
      Considerable local rearrangements exist during ligand binding processes when the
      system is searching for energy minima. The motion of the region that closes the
      beta-subunit during catalysis, the COMM domain, couples with the motion of the
      alpha-subunit, although the fluctuations are smaller than in the flexible loop
      regions. Because of multiple conformations of ligand-free TRPS in the open and
      partially closed states, the alpha-L6 loop fluctuations have preferential
      directionality, which may facilitate the fully closed conformations induced by
      alpha- and beta-substrates binding to both subunits. Such cooperative and
      directional motion may be a general feature that contributes to catalysis in many
      enzyme complexes.

PMID- 19764815
TI  - Expressed phosphorylase b kinase and its alphagammadelta subcomplex as regulatory
      models for the rabbit skeletal muscle holoenzyme.
AB  - Understanding the regulatory interactions among the 16 subunits of the
      (alphabetagammadelta)(4) phosphorylase b kinase (PhK) complex can only be
      achieved through reconstructing the holoenzyme or its subcomplexes from the
      individual subunits. In this study, recombinant baculovirus carrying a vector
      containing a multigene cassette was created to coexpress in insect cells alpha,
      beta, gamma, and delta subunits corresponding to rabbit skeletal muscle PhK. The
      hexadecameric recombinant PhK (rPhK) and its corresponding alphagammadelta
      trimeric subcomplex were purified to homogeneity with proper subunit
      stoichiometries. The catalytic activity of rPhK at pH 8.2 and its ratio of
      activities at pH 6.8 versus pH 8.2 were comparable to those of PhK purified from
      rabbit muscle (RM PhK), as was the hysteresis (autoactivation) in the rate of
      product formation at pH 6.8. Both the rPhK and alphagammadelta exhibited only a
      very low Ca(2+)-independent activity and a Ca(2+)-dependent activity similar to
      that of the native holoenzyme with [Ca(2+)](0.5) of 0.4 microM for the RM PhK,
      0.7 microM for the rPhK, and 1.5 microM for the alphagammadelta trimer. The RM
      PhK, rPhK, and alphagammadelta subcomplex were also all activated through self
      phosphorylation. Using cross-linking and limited proteolysis, the alpha-gamma
      intersubunit contacts previously observed within the intact RM PhK complex were
      also observed within the recombinant alphagammadelta subcomplex. Our results
      indicate that both the rPhK and alphagammadelta subcomplex are promising models
      for future structure-function studies on the regulation of PhK activity through
      intersubunit contacts, because both retained the regulatory properties of the
      enzyme purified from skeletal muscle.

PMID- 19764816
TI  - Transition state analogues rescue ribosomes from saporin-L1 ribosome inactivating
      protein.
AB  - Ribosome inactivating proteins (RIPs) catalyze the hydrolytic depurination of one
      or more adenosine residues from eukaryotic ribosomes. Depurination of the
      ribosomal sarcin-ricin tetraloop (GAGA) causes inhibition of protein synthesis
      and cellular death. We characterized the catalytic properties of saporin-L1 from
      Saponaria officinalis (soapwort) leaves, and it demonstrated robust activity
      against defined nucleic acid substrates and mammalian ribosomes. Transition state
      analogue mimics of small oligonucleotide substrates of saporin-L1 are powerful,
      slow-onset inhibitors when adenosine is replaced with the transition state mimic
      9-deazaadenine-9-methylene-N-hydroxypyrrolidine (DADMeA). Linear, cyclic, and
      stem-loop oligonucleotide inhibitors containing DADMeA and based on the GAGA
      sarcin-ricin tetraloop gave slow-onset tight-binding inhibition constants (K(i)*)
      of 2.3-8.7 nM under physiological conditions and bind up to 40000-fold tighter
      than RNA substrates. Saporin-L1 inhibition of rabbit reticulocyte translation was
      protected by these inhibitors. Transition state analogues of saporin-L1 have
      potential in cancer therapy that employs saporin-L1-linked immunotoxins.

PMID- 19764818
TI  - Strong hydrogen bond between glutamic acid 46 and chromophore leads to the
      intermediate spectral form and excited state proton transfer in the Y42F mutant
      of the photoreceptor photoactive yellow protein.
AB  - In the Y42F mutant of photoactive yellow protein (PYP) the photoreceptor is in an
      equilibrium between two dark states, the yellow and intermediate spectral forms,
      absorbing at 457 and 390 nm, respectively. The nature of this equilibrium and the
      light-induced protonation and structural changes in the two spectral forms were
      characterized by transient absorption, fluorescence, FTIR, and pH indicator dye
      experiments. In the yellow form, the oxygen of the deprotonated p
      hydroxycinnamoyl chromophore is linked by a strong low-barrier hydrogen bond to
      the protonated carboxyl group of Glu46 and by a weaker one to Thr50. Using FTIR,
      we find that the band due to the carbonyl of the protonated side chain of Glu46
      is shifted from 1736 cm(-1) in wild type to 1724 cm(-1) in the yellow form of
      Y42F, implying a stronger hydrogen bond with the deprotonated chromophore in
      Y42F. The FTIR data suggest moreover that in the intermediate spectral form the
      chromophore is protonated and Glu46 deprotonated. Flash spectroscopy (50 ns-10 s)
      shows that the photocycles of the two forms are essentially the same except for a
      transition around 5 mus that has opposite signs in the two forms and is due to
      the chemical relaxation between the two dark states. The two cycles are coupled,
      likely by excited state proton transfer. The Y42F cycle differs from wild type by
      the occurrence of a new intermediate with protonated chromophore between the
      usual I(1) and I(2) intermediates which we call I(1)H (370 nm). Transient
      fluorescence measurements indicate that in I(1)H the chromophore retains the
      orientation it had in I(1). Transient proton uptake occurs with a time constant
      of 230 mus and a stoichiometry of 1. No proton uptake was associated however with
      the formation of the I(1)H intermediate and the relaxation of the
      yellow/intermediate equilibrium. These protonation changes of the chromophore
      thus occur intramolecularly. The chromophore-Glu46 hydrogen bond in Y42F is
      shorter than in wild type, since the adjacent chromophore-Y42 hydrogen bond is
      replaced by a longer one with Thr50. This facilitates proton transfer from Glu46
      to the chromophore in the dark by lowering the barrier, leading to the
      protonation equilibrium and causing the rapid light-induced proton transfer which
      couples the cycles.

PMID- 19764817
TI  - Structure and inhibition of human diamine oxidase.
AB  - Humans have three functioning genes that encode copper-containing amine oxidases.
      The product of the AOC1 gene is a so-called diamine oxidase (hDAO), named for its
      substrate preference for diamines, particularly histamine. hDAO has been cloned
      and expressed in insect cells and the structure of the native enzyme determined
      by X-ray crystallography to a resolution of 1.8 A. The homodimeric structure has
      the archetypal amine oxidase fold. Two active sites, one in each subunit, are
      characterized by the presence of a copper ion and a topaquinone residue formed by
      the post-translational modification of a tyrosine. Although hDAO shares 37.9%
      sequence identity with another human copper amine oxidase, semicarbazide
      sensitive amine oxidase or vascular adhesion protein-1, its substrate binding
      pocket and entry channel are distinctly different in accord with the different
      substrate specificities. The structures of two inhibitor complexes of hDAO,
      berenil and pentamidine, have been refined to resolutions of 2.1 and 2.2 A,
      respectively. They bind noncovalently in the active-site channel. The inhibitor
      binding suggests that an aspartic acid residue, conserved in all diamine oxidases
      but absent from other amine oxidases, is responsible for the diamine specificity
      by interacting with the second amino group of preferred diamine substrates.

PMID- 19764821
TI  - Cob(I)alamin for trapping butadiene epoxides in metabolism with rat S9 and for
      determining associated kinetic parameters.
AB  - The reduced state of vitamin B(12), cob(I)alamin, acts as a supernucleophile that
      reacts ca. 10(5) times faster than standard nucleophiles, for example, thiols.
      Methods have been developed for trapping electrophilically reactive compounds by
      exploiting this property of cob(I)alamin. 1,3-Butadiene (BD) has recently been
      classified as a group 1 human carcinogen by the International Agency for Research
      on Cancer (IARC). The carcinogenicity of BD is considered to be dependent on the
      activation or deactivation of the reactive metabolites of BD, that is, the
      epoxides (oxiranes) 1,2-epoxy-3-butene (EB), 1,2:3,4-diepoxybutane (DEB), and 1,2
      epoxy-3,4-butanediol (EBdiol). Cytochrome P450 (P450) isozymes are involved in
      oxidation of BD to EB and further activation to DEB. EB and DEB are hydrolyzed by
      epoxide hydrolases (EH) to 3,4-dihydroxy-1-butene (BDdiol) and EBdiol,
      respectively. EBdiol can also be formed by oxidation of BDdiol. In the present
      study, cob(I)alamin was used for instant trapping of the BD epoxide metabolites
      generated in in vitro metabolism to study enzyme kinetics. The substrates EB,
      DEB, and BDdiol were incubated with rat S9 liver fraction, and apparent K(m) and
      apparent V(max), were determined. The ratio of conversion of EB to DEB (by P450)
      to the rate of deactivation of DEB by EH was 1.09. Formation of EBdiol from
      hydrolysis of DEB was ca. 10 times faster than that from oxidation of BDdiol. It
      was also found that the oxidation of EB to DEB was much faster than that of
      BDdiol to EBdiol. The study offers comparative enzyme kinetic data of different
      BD metabolic steps, which is useful for quantitative interspecies comparison.
      Furthermore, a new application of cob(I)alamin was demonstrated for the
      measurement of enzyme kinetics of compounds that form electophilically reactive
      metabolites.

PMID- 19764822
TI  - Scanning the cell surface proteome of cancer cells and identification of
      metastasis-associated proteins using a subtractive immunization strategy.
AB  - Identification of the cell surface proteome and comparison of their expression
      between cells with different phenotypic characteristics is crucial to the
      discovery of novel cancer drug targets as well as elucidating the basic biologic
      processes of cancer. However, cell surface proteomics are complex and
      technologically challenging, and no ideal method is currently available. Here, we
      describe a strategy that allows scanning of the entire cell surface and
      identification of molecules that exhibit altered expression between two cell
      types. Concurrently, this method gives rise to valuable reagents for further
      characterization of the identified proteins. The strategy is based on subtractive
      immunization of mice, and we used the two isogenic cell lines, NM-2C5 and M-4A4,
      derived from the MDA-MB-435 cancer cell line, as a model system. Although the two
      cell lines are equally tumorigenic, only M-4A4 has metastatic capabilities. Our
      results yielded a large panel of monoclonal antibodies (mAbs) that recognized
      cell surface markers preferentially or exclusively expressed on metastatic vs
      nonmetastatic cancer cells. Four mAbs and their corresponding antigens were
      further characterized. Importantly, analysis on an extended panel of breast
      cancer cell lines demonstrated that the four mAbs bound preferentially to cell
      lines known to be metastatic in vivo, suggesting that these markers have general
      applications. Immunohistochemical analysis showed that mAb 11E6 reacted
      preferentially with neuroendocrine tumors while exhibiting no or very weak
      reactivity with normal tissues. mAb 15C7 stained a variety of cancers as well as
      some normal lymphoid organs and was subsequently identified to react with HLA-DR
      beta. A third mAb, 31D7, that also specifically recognized HLA-DR-beta was
      capable of inhibiting the growth of MZ2 melanoma cells in vitro. Further, we
      found that the reduced expression of HLA-DR antigens in nonmetastatic cells of
      this model was not regulated by class II transactivator, but by
      posttranscriptional mechanisms. The study demonstrates the advantage of using the
      exquisitely discriminating recognition system of the immune system itself to scan
      the cell surface proteome for differentially expressed proteins. The subtractive
      immunization strategy should be broadly applicable as a quantitative and
      comparative proteomic approach for screening the cell surface and also allow
      generation of mAbs to study these cell surface antigens in more detail.

PMID- 19764823
TI  - Proteomic profiling of cervical and lumbar spinal cord reveals potential
      protective mechanisms in the wobbler mouse, a model of motor neuron degeneration.
AB  - The wobbler mouse is a model of selective motor neuron degeneration in the
      cervical spinal cord. Comparing cervical and lumbar tracts of control and
      diseased mice at the early stage of pathology by proteomic analysis, we
      identified 31 proteins by peptide mass fingerprint after tryptic digestion and
      MALDI-TOF analysis, that were differently represented among the four experimental
      groups. In healthy mice, patterns of protein expression differed between cervical
      and lumbar tract: proteins of cellular energetic metabolism pathway showed lower
      expression in the cervical tract, while cellular trafficking proteins were
      overrepresented. In wobbler mice, these differences disappeared and the
      expression pattern was similar between cervical and lumbar spinal cord. We found
      that most of the proteins differentially regulated in wobbler with respect to
      control cervical tract were related to astrogliosis or involved in glutamate
      glutamine cycle, energy transduction and redox functions. Proteins
      overrepresented in the wobbler lumbar spinal cord were cytoskeleton proteins and
      cellular transport proteins, in particular the vesicle fusing ATPase and the
      isoform 2 of syntaxin-binding protein 1, involved in vesicle trafficking. We
      suggest that overexpression of proteins involved in vesicle trafficking, together
      with proteins counteracting mitochondrial dysfunction can have neuroprotective
      effects, preserving lumbar spinal cord motor neurons in wobbler mice.

PMID- 19764824
TI  - Accommodation needs for carers of and adults with intellectual disability in
      regional Australia: their hopes for and perceptions of the future.
AB  - INTRODUCTION: This article provides an in-depth investigation of the
      accommodation circumstances of a population of aging adults with intellectual
      disability living at home with parents or in supported accommodation in an
      Australian regional centre. Given the ageing of both the carer and adult
      population with intellectual disability our research explored the accommodation
      needs and perceptions of future lifestyle issues from the perspective of both the
      carers and the adults with intellectual disability. This study aimed to describe
      these accommodation circumstances related to a regional/rural location and did
      not make direct comparisons with urban/metropolitan situations. METHODS: A mixed
      methods approach, specifically an explanatory design, participant selection model
      was utilised for the overall study. This article reports on the qualitative study
      consisting of data from both free response open-ended survey questions and semi
      structured interviews with selected adults with intellectual disability and their
      carers. This study explored and described participants' experiences and
      perceptions regarding their accommodation needs and future lifestyle issues. A
      purposive sampling technique was used to identify a representative sample of
      participants for interviews. The interview questions were guided by the results
      of the quantitative first study phase. Data were analysed by content analysis for
      major themes emerging from the interview and free response survey data. RESULTS:
      A total of 146 carers (mean age 61.5 years; range 40-91 years) and 156 adults
      with intellectual disability (mean age 37.2 years; range 18-79 years)
      participated in the study. Data saturation was reached after 10 interviews were
      undertaken with carers (mean age 60 years) and 10 with adults with intellectual
      disability (no age criteria applied). Six major themes were identified: ageing,
      family issues, living at home, living away from home, government support and
      funding, and future needs. The perceptions and views of both adults with
      intellectual disability and their carers around these major themes are reported
      and discussed. CONCLUSIONS: This study indicates that there is a lack of
      suitable, available, supported accommodation for people aged 18 years and older
      with intellectual disability in this Australian regional centre. Consequently,
      aging parents caring at home have little choice but to continue in their caring
      role. For those caring away from home, existing services are decreasingly seen as
      fitting the ideal life they want for the person with intellectual disability for
      whom they care. The told experiences, perceptions and views of older carers of
      and adults with intellectual disability have highlighted their increasing
      vulnerability to the 'disability system'. The findings suggest that government
      and disability services must acknowledge the changing needs of people with
      intellectual disability in connection with their advancing age and the urgency of
      increasing care needs due to the advancing age of their carer's. The overwhelming
      feeling is that the carer's voice will only be heard when the situation reaches
      crisis point. For many carers and their families this has already occurred.

PMID- 19764825
TI  - Sciatic nerve injury model in the axolotl: functional, electrophysiological, and
      radiographic outcomes.
AB  - OBJECT: The 2 aims of this study were as follows: 1) to establish outcome
      measures of nerve regeneration in an axolotl model of peripheral nerve injury;
      and 2) to define the timing and completeness of reinnervation in the axolotl
      following different types of sciatic nerve injury. METHODS: The sciatic nerves in
      36 axolotls were exposed bilaterally in 3 groups containing 12 animals each:
      Group 1, left side sham, right side crush; Group 2, left side sham, right side
      nerve resected and proximal stump buried; and Group 3 left side cut and sutured,
      right side cut and sutured with tibial and peroneal divisions reversed. Outcome
      measures included the following: 1) an axolotl sciatic functional index (ASFI)
      derived from video swim analysis; 2) motor latencies; and 3) MR imaging
      evaluation of nerve and muscle edema. RESULTS: For crush injuries, the ASFI
      returned to baseline by 2 weeks, as did MR imaging parameters and motor
      latencies. For buried nerves, the ASFI returned to 20% below baseline by 8 weeks,
      with motor evoked potentials present. On MR imaging, nerve edema peaked at 3 days
      postintervention and gradually normalized over 12 weeks, whereas muscle
      denervation was present until a gradual decrease was seen between 4 and 12 weeks.
      For cut nerves, the ASFI returned to 20% below baseline by Week 4, where it
      plateaued. Motor evoked potentials were observed at 2-4 weeks, but with an
      increased latency until Week 6, and MR imaging analysis revealed muscle
      denervation for 4 weeks. CONCLUSIONS: Multiple outcome measures in which an
      axolotl model of peripheral nerve injury is used have been established. Based on
      historical controls, recovery after nerve injury appears to occur earlier and is
      more complete than in rodents. Further investigation using this model as a
      successful "blueprint" for nerve regeneration in humans is warranted.

PMID- 19764826
TI  - Use of a vascular reconstruction device to salvage acute ischemic occlusions
      refractory to traditional endovascular recanalization methods.
AB  - OBJECT: Acute revascularization has been associated with improved stroke
      outcomes. The Prolyse in Acute Cerebral Thromboembolism (PROACT II) trial
      achieved recanalization rates of 66%. The Multi Mechanical Embolus Removal in
      Cerebral Ischemia (Multi MERCI) trial achieved recanalization in 70% of patients.
      However, these interventional tools are not always successful. The Enterprise
      vascular reconstruction device was recently introduced for treatment of cerebral
      aneurysms previously untreatable with endovascular techniques. The authors
      evaluated a multicenter experience using this stent as a salvage
      revascularization tool for acute stroke treatment. METHODS: Four medical centers
      participated in a retrospective review of endovascularly treated patients with
      acute stroke for cases treated with the Enterprise stent after routine
      interventions had been unsuccessful. Data collected included preprocedure
      information, intraprocedure findings, and outcomes. RESULTS: Twenty patients with
      acute stroke (mean age 61.6 +/- 22 years) were treated with the Enterprise stent.
      Ten patients received intravenous recombinant tissue plasminogen activator before
      catheter intervention, without improvement. Intraarterial interventions attempted
      unsuccessfully before Enterprise deployment included the Merci retriever (12
      patients), angioplasty (7 patients), glycoprotein IIb-IIIa inhibitor
      administration (12 patients), intraarterial nitroglycerin (1 patient), Wingspan
      stent deployment (3 patients), and Xpert stent deployment (1 patient). The mean
      preintervention National Institutes of Health Stroke Scale (NIHSS) score was 17
      +/- 6 (median 17). All patients presented with a Thrombolysis in Myocardial
      Infarction (TIMI) score of 0 or 1. Revascularization was achieved in all patients
      (75% with a TIMI score of 3, 25% with a TIMI score of 2). Improvement (> or = 4
      points on the NIHSS) was documented in 75% of patients. Mean NIHSS improvement
      from intervention to discharge was 8 +/- 7 points (median 9 points). CONCLUSIONS:
      These preliminary data suggest a potential benefit to the use of the Enterprise
      stent when routine intervention methods fail.

PMID- 19764827
TI  - Efficacy of silver-bearing external ventricular drainage catheters: a
      retrospective analysis.
AB  - OBJECT: Catheter-related infection of CSF is a potentially life-threatening
      complication of external ventricular drainage (EVD). When using EVD catheters,
      contact between the ventricular system and skin surface occurs and CSF infection
      is possible. The aim of this analysis was to compare the efficacy of silver
      bearing EVD catheters for reducing the incidence of infection with standard
      nonimpregnated EVD catheters in neurosurgical patients with acute hydrocephalus.
      METHODS: Two hundred thirty-one consecutive patients were retrospectively
      reviewed. Of these, 164 were enrolled in the final analysis. Six patient charts
      were incomplete or missing, 15 patients were excluded because of catheter
      insertion within the previous 30 days, 6 because of a suspected CSF infection
      before ventriculostomy, 7 because the catheter was removed < 24 hours after
      insertion, and 33 patients because of the requirement of bilateral
      ventriculostomy. The control group with standard nonimpregnated EVD catheters
      consisted of 90 patients. The study group with silver-bearing EVDs consisted of
      74 patients. For assessing the primary outcome, the authors recorded all CSF
      samples and liquor cell counts routinely obtained in sterile fashion. After
      removal of the catheters, they also reviewed microbiology reports of the removed
      catheters to assess colonization of the catheter tips. RESULTS: The occurrence of
      a positive CSF culture, colonization of the catheter tip, or liquor pleocytosis
      (white blood cell count > 4/microl) was approximately 2 times less in the study
      group with silver-bearing EVD catheters than that in the control group (18.9%
      compared with 33.7%, p = 0.04). Positive CSF cultures alone occurred 2 times less
      frequently for microorganisms in the study group (2.7% compared with 4.7%, p =
      0.55). Silver-bearing catheters were 4 times less likely to become colonized as
      nonimpregnated EVDs (1.4% compared with 5.8%, p = 0.14). Liquor pleocytosis was
      half as likely in the study group (17.6% compared with 30.2%, p = 0.06).
      CONCLUSIONS: Although of limited sample size and thus underpowered for subgroup
      analysis, this analysis indicates that EVD catheters impregnated with silver
      nanoparticles and an insoluble silver salt may reduce the risk of catheter
      related infections in neurosurgical patients.

PMID- 19764828
TI  - Motoneuron survival after chronic and sequential peripheral nerve injuries in the
      rat.
AB  - OBJECT: Surgical repair of peripheral nerves following chronic nerve injury is
      associated with poor axonal regeneration and outcome. An underlying possibility
      is that chronic injuries may increase motoneuron cell death. The hypothesis that
      substantial motoneuron death follows chronic and sequential nerve injuries was
      tested in adult rats in this study. METHODS: Thirty adult male Lewis rats
      underwent bilateral multistage surgeries. At initial surgery, Fast Blue (FB)
      tracer was injected at a nerve-crush injury site in the right control femoral
      motor nerve. The left femoral motor nerve was transected at the same level and
      either capped to prevent regeneration (Group 1), or repaired to allow axonal
      regeneration and reinnervation of the target quadriceps muscle (Group 2) (15 rats
      in each group). After 8 weeks in 6 rats/group, the left femoral nerve was cut and
      exposed to FB just proximal to prior nerve capping or repair and the rats were
      evaluated for FB-labeled motoneuron counts bilaterally in the spinal cord (this
      was considered survival after initial injury). In the remaining 9 animals/group,
      the left nerve was recut (sequential injury), exposed to FB, and repaired to a
      fresh distal saphenous nerve stump to permit axonal regeneration. Following
      another 6 weeks, Fluoro-Gold, a second retrograde tracer, was applied to the cut
      distal saphenous nerve. This allowed us to evaluate the number of motoneurons
      that survived (maintained FB labeling) and the number of motoneurons that
      survived but that also regenerated axons (double labeled with FB and Fluoro
      Gold). RESULTS: A mean number of 350 and 392 FB-labeled motoneurons were found
      after 8 weeks of nerve injury on the right and the left sides, respectively. This
      indicated no significant cell death due to initial nerve injury alone. A similar
      number (mean 390) of motoneurons were counted at final end point at 14 weeks,
      indicating no significant cell death after sequential and chronic nerve injury.
      However, only 50% (mean 180) of the surviving motoneurons were double labeled,
      indicating that only half of the population regenerated their axons. CONCLUSIONS:
      The hypothesis that significant motoneuron cell death occurs after chronic and or
      sequential nerve injury was rejected. Despite cell survival, only 50% of
      motoneurons are capable of exhibiting a regenerative response, consistent with
      our previous findings of reduced regeneration after chronic axotomy.

PMID- 19764829
TI  - Radiosurgery for large-volume (> 10 cm3) benign meningiomas.
AB  - OBJECT: Stereotactic radiosurgery (SRS) has proven to be a safe and effective
      treatment for many patients with intracranial meningiomas. Nevertheless, the
      morbidity associated with radiosurgery of larger meningiomas is poorly
      understood. METHODS: The authors performed a retrospective review of 116 patients
      who underwent SRS for meningiomas (WHO Grade I) > 10 cm3 between 1990 and 2007,
      with a minimum follow-up of 12 months. Patients with atypical or malignant
      meningiomas and those who received prior radiotherapy were excluded. The average
      tumor volume was 17.5 cm3 (range 10.1-48.6 cm3); the average tumor margin dose
      was 15.1 Gy (range 12-18 Gy); and the mean follow-up duration was 70.1 months
      (range 12-199 months). RESULTS: Tumor control was 99% at 3 years and 92% at 7
      years after radiosurgery. Thirty complications after radiosurgery were noted in
      27 patients (23%), including 7 cases of seizures, 6 cases of hemiparesis, 5 cases
      of trigeminal injury, 4 cases of headaches, 3 cases of diplopia, 2 cases each of
      cerebral infarction and ataxia, and 1 case of hearing loss. Patients with
      supratentorial tumors experienced a higher complication rate compared with
      patients with skull base tumors (44% compared with 18%) (hazard ratio 2.9, 95% CI
      1.3-6.7, p = 0.01). CONCLUSIONS: The morbidity associated with SRS for patients
      with benign meningiomas > 10 cm(3) is greater for supratentorial tumors compared
      with skull base tumors. Whereas radiosurgery is relatively safe for patients with
      large-volume skull base meningiomas, resection should remain the primary disease
      management for the majority of patients with large-volume supratentorial
      meningiomas.

PMID- 19764830
TI  - Support needs of informal hospice caregivers: a qualitative study.
AB  - BACKGROUND: Informal caregivers of hospice patients experience multiple stressors
      that can negatively impact physical, psychological, and emotional health. The
      goal of this qualitative study was to understand caregivers' needs to inform the
      feasibility, structure, and content of a telephone-based counseling intervention.
      METHODS: Focus groups and interviews with 36 former hospice caregivers and 11
      hospice staff from 6 hospices were conducted. Interviews and focus groups were
      audio-recorded, transcribed, and analyzed using a constant comparative approach.
      RESULTS: Key content areas included coping, emotional support, self-care,
      logistical issues, and bereavement. Respondents supported telephone-based
      counseling, appreciating its relative anonymity and convenience. It was
      recommended that calls be initiated by the counselor, on a weekly basis, and that
      one counselor be assigned to each caregiver. Hospice staff emphasized the need to
      coordinate telephone counseling with hospice care, scheduling around and
      communicating with hospice staff. Most caregivers indicated that they would
      participate in telephone-based counseling were it available; hospice staff
      thought that half of caregivers would participate. A pervasive theme was that
      "there can never be enough support for a caregiver." CONCLUSION: Informal
      caregivers of hospice patients have support needs that are amenable to telephone
      based counseling designed to be complementary to existing hospice services. Based
      on these qualitative findings, we are pilot-testing a telephone-based cognitive
      behavioral stress management program for informal caregivers of hospice patients.

PMID- 19764831
TI  - Malaria and iron: history and review.
AB  - To cause infection, nearly all protozoa, fungi, and bacteria must obtain growth
      essential iron from their hosts. To suppress infection, hosts have evolved iron
      withholding defense systems. Enhancement of iron withholding is a potential
      target for the development of novel therapeutic agents. This review focuses on
      the association of iron with current and emerging antimalarial drugs. Proposed
      mechanisms of antimalarial action of (1) iron-requiring agents, the artemisinins,
      are compared with (2) a spectrum of compounds that withdraw iron by chelation. A
      novel approach to malarial chemotherapy might involve the sequential use of a
      member of each of the two categories.

PMID- 19764833
TI  - 2nd Annual Symposium on Self Monitoring of Blood Glucose (SMBG) Applications and
      Beyond, May 7-10, 2009, Berlin, Germany.

PMID- 19764834
TI  - New and improved methods to characterize glycemic variability using continuous
      glucose monitoring.
AB  - BACKGROUND: Glycemic variability is a possible risk factor for development of
      complications from diabetes. Numerous methods have been used to characterize
      glycemic variability. METHODS: We propose several new methods to characterize
      glycemic variability. We evaluated these methods empirically and theoretically
      and compared them with previous methods. RESULTS: We describe (1) extension and
      generalization of the mean amplitude of glycemic excursion (MAGE), i.e., "within
      day variability," (2) extension and generalization of the mean of daily
      differences (MODD), i.e., the "between day-within time points variability," (3)
      "between daily means variability," (4) "between time points variability" of the
      glucose profile averaged over several days, (5) "within series variability" for a
      time segment of any arbitrary length, (6) new measures of the stability of the
      daily glycemic patterns, (7) new types of graphical displays, including within
      day variability, between day-within time points variability, and between daily
      means variability versus total variability, and between daily means variability
      versus within day variability, and (8) new methods to evaluate whether within
      series and between day-within time points variability fluctuate systematically by
      time of day. We examined the new measures in relation to previous measures of
      glycemic variability using correlation analysis on a clinical dataset for 85
      subjects. MAGE, MODD, and continuous overall net glycemic action (CONGA(n)) are
      directly proportional to total standard deviation (SD). MAGE is highly correlated
      with both total SD and within day variability but weakly correlated with measures
      of between day variability. MODD is highly correlated with between day-within
      time points variability and total SD but weakly correlated with measures of
      within day variability. CONCLUSIONS: We provide a systematic, logical framework
      to characterize multiple aspects of glycemic variability and have implemented a
      simple, practical computing format. This approach can help clinical researchers
      and clinicians identify the major sources of variability for any given patient
      and monitor responses to interventions.

PMID- 19764835
TI  - Socioeconomic differences in preferences and willingness-to-pay for insulin
      delivery systems in type 1 and type 2 diabetes.
AB  - BACKGROUND: An evaluation of patients' preferences is necessary to understand the
      demand for different insulin delivery systems. The aim of this study was to
      investigate the association between socioeconomic status (SES) and patients'
      preferences and willingness to pay (WTP) for various attributes of insulin
      administration for diabetes management. METHODS: We conducted a discrete choice
      experiment (DCE) to determine patients; preferences and their WTP for
      hypothetical insulin treatments. Both self-reported annual household income and
      education completed were used to explore differences in treatment preferences and
      WTP for different attributes of treatment across different levels of SES.
      RESULTS: The DCE questionnaire was successfully completed by 274 patients.
      Overall, glucose control was the most valued attribute by all socioeconomic
      groups, while route of insulin delivery was not as important. Patients with
      higher incomes were willing to pay significantly more for better glucose control
      and to avoid adverse events compared to lower income groups. In addition, they
      were willing to pay more for an oral short-acting insulin ($Can 71.65 [95%
      confidence interval, $40.68, $102.62]) compared to the low income group ($Can
      9.85 [95% confidence interval, 14.86, 34.56; P < 0.01]). Conversely, there were
      no differences in preferences when the sample was stratified by level of
      education. CONCLUSIONS: This study revealed that preferences and WTP for insulin
      therapy are influenced by income but not by level of education. Specifically, the
      higher the income, the greater desire for an oral insulin delivery system,
      whereas an inhaled route becomes less important for patients.

PMID- 19764832
TI  - Redox regulation of DNA repair: implications for human health and cancer
      therapeutic development.
AB  - Redox reactions are known to regulate many important cellular processes. In this
      review, we focus on the role of redox regulation in DNA repair both in direct
      regulation of specific DNA repair proteins as well as indirect transcriptional
      regulation. A key player in the redox regulation of DNA repair is the base
      excision repair enzyme apurinic/apyrimidinic endonuclease 1 (APE1) in its role as
      a redox factor. APE1 is reduced by the general redox factor thioredoxin, and in
      turn reduces several important transcription factors that regulate expression of
      DNA repair proteins. Finally, we consider the potential for chemotherapeutic
      development through the modulation of APE1's redox activity and its impact on DNA
      repair.

PMID- 19764836
TI  - Effect of insulin catheter wear-time on subcutaneous adipose tissue blood flow
      and insulin absorption in humans.
AB  - BACKGROUND: Insertion of an insulin catheter for continuous subcutaneous insulin
      infusion into the subcutaneous adipose tissue (SAT) causes a tissue trauma that
      may have consequences for insulin absorption. We evaluated the importance of
      insulin catheter wear-time on subcutaneous adipose tissue blood flow (ATBF) and
      absorption of the rapid-acting insulin analog insulin aspart over a period of 4
      days. METHODS: Teflon insulin catheters (Medtronic, Minneapolis, MN) were
      inserted into the abdominal SAT of 10 healthy men without diabetes (mean +/- SEM
      age, 23.0 +/- 1.1 years; body mass index, 22.1 +/- 0.7 kg/m(2)) and connected to
      an insulin pump delivering a constant rate of isotonic saline for 4 days.
      Subjects participated in four study days (days 0, 1, 2, and 4) during which ATBF
      around the catheter tip was measured by (133)Xe clearance and absorption of an
      insulin aspart bolus (0.1 U/kg) was measured for 4 h. RESULTS: ATBF increased
      from day 0 to day 2 after catheter insertion (2.6 +/- 0.6 to 4.5 +/- 0.8 mL/100
      g/min; P = 0.030). By day 4, ATBF had returned to day 0 level. Time to peak
      plasma insulin aspart concentration after bolus administration decreased with
      catheter wear-time from 55 +/- 3 min on day 0 to 45 +/- 4 min on day 4 (P =
      0.019). Neither peak plasma concentration nor area under the curve of insulin
      aspart changed significantly. CONCLUSIONS: Insertion of a Teflon insulin catheter
      into the SAT results in increased ATBF and faster absorption of insulin aspart in
      a period of 4 days without any change in the total amount of insulin aspart
      absorbed.

PMID- 19764837
TI  - A comparison of injection force and dosage scale size between NovoPen 3 and
      NovoPen 4.
AB  - BACKGROUND: Easy-to-use insulin devices are an important tool in the treatment of
      diabetes. In this study, injection force requirements and dosage scale displays
      were evaluated for NovoPen 3 and NovoPen 4 (both from Novo Nordisk A/S,
      Copenhagen, Denmark). METHODS: To simulate 5 years of expected lifetime usage,
      5,475 injections were performed automatically. Before and after lifetime testing,
      the force required to expel 60 U of insulin from NovoPen 3 and NovoPen 4 with 30
      gauge or 31-gauge needles was measured. To compare dosage scale displays, digital
      images of multiple settings were made, and the total inked areas of digits were
      converted to mm(2). RESULTS: At baseline, the mean +/- SD injection force of
      NovoPen 4 was 9.14 +/- 0.87 N and 16.55 +/- 1.17 N, which was significantly lower
      (P < 0.001) than for NovoPen 3, at 18.36 +/- 1.06 N and 29.81 +/- 1.26 N, with
      the 30-gauge and 31-gauge needle, respectively. After simulated lifetime testing,
      mean +/- SD injection force was 10.93 +/- 0.77 N and 17.77 +/- 1.14 N for NovoPen
      4, which was significantly lower than the injection force of 18.54 +/- 0.94 N and
      31.69 +/- 1.98 N for NovoPen 3 (P < 0.001). The mean dosage scale digit size was
      1.63 mm(2) for NovoPen 3 and 7.82 mm(2) for NovoPen 4, with a mean difference of
      6.19 mm(2). The display for NovoPen 4 was 4.74 times larger (P < 0.001).
      CONCLUSIONS: The mean injection force required to operate NovoPen 4 was reduced
      up to 50% compared with NovoPen 3 (P < 0.001), and the mean dosage display for
      NovoPen 4 was over four times larger than for NovoPen 3 (P < 0.001). Based on
      these findings, patients with diabetes who have manual or visual impairment
      should find it easier to dose insulin with NovoPen 4.

PMID- 19764838
TI  - Accuracy and precision of four value-added blood glucose meters: the Abbott
      Optium, the DDI Prodigy, the HDI True Track, and the HypoGuard Assure Pro.
AB  - PURPOSE: This study compared the accuracy and precision of four value-added
      glucose meters. METHODS: Finger stick glucose measurements in diabetes patients
      were performed using the Abbott Diabetes Care (Alameda, CA) Optium, Diagnostic
      Devices, Inc. (Miami, FL) DDI Prodigy, Home Diagnostics, Inc. (Fort Lauderdale,
      FL) HDI True Track Smart System, and Arkray, USA (Minneapolis, MN) HypoGuard
      Assure Pro. Finger glucose measurements were compared with laboratory reference
      results. Accuracy was assessed by a Clarke error grid analysis (EGA), a Parkes
      EGA, and within 5%, 10%, 15%, and 20% of the laboratory value criteria (chi2
      analysis). Meter precision was determined by calculating absolute mean
      differences in glucose values between duplicate samples (Kruskal-Wallis test).
      RESULTS: Finger sticks were obtained from 125 diabetes patients, of which 90.4%
      were Caucasian, 51.2% were female, 83.2% had type 2 diabetes, and average age of
      59 years (SD 14 years). Mean venipuncture blood glucose was 151 mg/dL (SD +/-65
      mg/dL; range, 58-474 mg/dL). Clinical accuracy by Clarke EGA was demonstrated in
      94% of Optium, 82% of Prodigy, 61% of True Track, and 77% of the Assure Pro
      samples (P < 0.05 for Optium and True Track compared to all others). By Parkes
      EGA, the True Track was significantly less accurate than the other meters. Within
      5% accuracy was achieved in 34%, 24%, 29%, and 13%, respectively (P < 0.05 for
      Optium, Prodigy, and Assure Pro compared to True Track). Within 10% accuracy was
      significantly greater for the Optium, Prodigy, and Assure Pro compared to True
      Track. Significantly more Optium results demonstrated within 15% and 20% accuracy
      compared to the other meter systems. The HDI True Track was significantly less
      precise than the other meter systems. CONCLUSIONS: The Abbott Optium was
      significantly more accurate than the other meter systems, whereas the HDI True
      Track was significantly less accurate and less precise compared to the other
      meter systems.

PMID- 19764839
TI  - Variation of fasting serum C-peptide level after admission in Japanese patients
      with type 2 diabetes mellitus.
AB  - BACKGROUND: The aim of this study was to evaluate the variation of fasting serum
      C-peptide (S-CPR) levels, as a marker for endogenous insulin secretion after
      admission in Japanese patients with type 2 diabetes mellitus (T2DM). METHODS: S
      CPR levels together with other metabolic factors were measured in 234 T2DM
      patients twice: at the beginning and at the end of admission for the control of
      blood sugar levels. As a result, patients were classified into two groups
      according to their changes of S-CPR (DeltaS-CPR), which consisted of patients
      whose S-CPR levels had decreased (group D) and increased (group I) after
      admission. RESULTS: Patients allocated to group I showed younger age, shorter
      duration of diabetes, and lower basal S-CPR level compared to group D.
      Conversely, patients in group D showed higher levels of high-sensitivity C
      reactive protein (HS-CRP) and brachial-ankle pulse wave velocity compared to
      group I, suggesting patients in this group are prone to atherosclerosis. DeltaS
      CPR was positively correlated with the change of body mass index, waist
      circumference, and triglycerides in group D. On the other hand, DeltaS-CPR was
      negatively correlated with the change of HS-CRP in group I, indicating residual
      beta-cell function could be recovered by the amelioration of inflammatory status
      in pancreatic islets. CONCLUSIONS: It is plausible that Japanese T2DM patients
      could be classified according to the variation of S-CPR after admission.
      Evaluation of basal and the variation of S-CPR could provide advantageous
      information for the management of diabetes mellitus or related disorders.

PMID- 19764840
TI  - Magnitude and determinants of ocular morbidities among persons with diabetes in a
      project in Ahmedabad, India.
AB  - BACKGROUND: Visual disabilities due to diabetes are on the rise, especially in
      urban areas of developing countries. Proper health planning will need evidence
      based information. STUDY DESIGN AND METHODS: We estimated the prevalence and
      identified the determinants of eye complications among persons with diabetes
      screened in Ahmedabad, India, during 2007-2008. This was a review of the data
      from a health institution-based project. Physicians collected information on
      diabetes, and ophthalmologists examined the patients for visual acuity, diabetic
      retinopathy (DR), glaucoma, and cataracts. World Health Organization-recommended
      grading of DR was used. Frequencies, prevalence, and 95% confidence interval (CI)
      values were calculated. RESULTS: Of 40,919 persons who we examined for diabetes,
      9,246 (66.6%) persons knew that they had diabetes, whereas 4,641 (33.4%) persons
      were detected with diabetes for the first time. The prevalence of DR, early
      cataract, and glaucoma among those who knew that they had diabetes was 14.6% (95%
      CI 13.9-15.3), 44.4% (95% CI 43.4-45.4), and 5.4% (95% CI 4.9-5.9), respectively.
      The prevalence of DR among persons with diabetes (new and old) was 10.1% (95% CI
      9.6-10.6). Although poor vision was positively associated with DR (chi2 = 706),
      40% of those with DR had vision better than 20/60. Male sex (odds ratio [OR] =
      1.31), longer duration of diabetes (chi2 = 1,808), hypertension (OR = 1.13), good
      sugar control (OR = 0.09), and nephropathy (OR = 2.16) were the factors
      associated with DR. Regression analysis suggested that longer duration of
      diabetes and poor control of diabetes were the predictors of DR. CONCLUSIONS: The
      prevalence of DR was low. Long duration of diabetes, poor control of blood sugar,
      presence of nephropathy, and hypertension were associated with DR. Good vision
      could mislead about the severity of DR.

PMID- 19764841
TI  - Dose accuracy of SoloSTAR and FlexPen as assessed in a clinical setting.
AB  - AIMS: This study aimed to compare the accuracy of SoloSTAR(sanofi-aventis, Paris,
      France) and FlexPen (Novo Nordisk, Bagsvaerd, Denmark) to deliver doses of
      insulin when used by insulin/device-naive people attending a local healthcare
      practice. METHODS: For the determination of dose accuracy, SoloSTAR containing
      insulin glargine (lot 672) and FlexPen containing insulin aspart (lot SH70557)
      were used for all tests. The participants were given instruction by an
      independent monitor on how to use the pens. To be consistent, users were trained
      to hold the pens in situ for 10 s at the end of injection to ensure that the full
      dose was injected. Forty-eight subjects performed three dose deliveries of 20
      units (into a sponge) with each pen type. The method of injecting into a sponge
      aimed to mimic real-life practice; this approach is commonly used to ensure the
      patient has a correct injection technique before the patient self-administers the
      injection. RESULTS: The delivery (n = 144) of individual doses of 20 units was
      not statistically different (P = 0.187) between SoloSTAR (mean +/- SD, 19.75 +/-
      0.30 units) and FlexPen (19.80 +/- 0.33 units). In total, 2% of doses from both
      devices were <19 units; 98% were within 19-21 units. CONCLUSIONS: Both SoloSTAR
      and FlexPen were similarly accurate when used by device-naive subjects to deliver
      20-unit doses of insulin. This is likely to have beneficial clinical effects in
      terms of glycemic control, as well as improved patient confidence that insulin
      pens accurately deliver doses of insulin.

PMID- 19764842
TI  - Comparison of different anthropometric indices for identifying insulin resistance
      in schoolchildren.
AB  - OBJECTIVES: Anthropometric indices have been associated with insulin resistance
      in children. This study (1) determined the association between insulin resistance
      and anthropometric indices, including body mass index (BMI), waist circumference
      (WC), WC/height, weight/(sitting height)(2), and WC/sitting height, and (2)
      compared the abilities of these five indices to identify children with insulin
      resistance. METHODS: Data were collected from six elementary schools in Argentina
      between April and August 2007. Anthropometric data and Tanner staging were
      obtained. Fasting serum concentrations of glucose, lipids, and insulin were
      measured. RESULTS: Six hundred twenty-five children (318 boys) between 6 and 14
      years old were examined. The mean age of the children was 9.6 +/- 2.0 years.
      Ninety-six (15.4%) of the children were obese, 91 (14.6%) were overweight, and
      438 (70.1%) were normal weight using Centers for Disease Control and Prevention
      norms. Sixty percent, 23.0%, 14.0%, and 3.0% were Tanner stage I, II, III, and
      IV, respectively. The areas under the receiver operator characteristic curves
      were as follows: WC = 0.78 +/- 0.021 (95% confidence interval [CI] 0.74-0.82),
      BMI = 0.77 +/- 0.022 (95% CI 0.73-0.82), weight/(sitting height)(2) = 0.76 +/-
      0.022 (95% CI 0.72-0.81), WC/height = 0.67 +/- 0.027 (95% CI 0.62-0.72), and
      WC/sitting height = 0.67 +/- 0.27 (95% CI 0.62-0.72), indicating that BMI, WC,
      and weight/(sitting height)(2) were acceptable predictors for insulin resistance,
      whereas WC/height and WC/sitting height were fair predictors as the areas under
      the curve were <0.7. CONCLUSIONS: This study suggests that WC and BMI are (and
      remain) the best correlates for insulin resistance. In contrast, the indices of
      the ratio between WC and height were fair predictors for insulin resistance.
      Additional longitudinal studies should be done to further confirm these findings.

PMID- 19764843
TI  - Effect of hospital setting and volume on clinical outcomes in women with
      gestational and type 2 diabetes mellitus.
AB  - OBJECTIVE: Efforts to improve health care outcomes in the United States have led
      some organizations to recommend specific hospital settings or case volumes for
      complex medical diagnoses and procedures. But there are few studies of the effect
      of setting and volume on maternal outcomes, particularly in complicated
      conditions, such as diabetes. Our objective was to estimate the effect of
      hospital setting and volume on childbirth morbidity and length of stay in
      pregnancies complicated by type 2 and gestational diabetes. METHODS: We analyzed
      Maryland hospital discharge data during 1999-2004. The dependent variables were
      primary cesarean delivery, episiotomy, a composite variable for severe maternal
      morbidity, and hospital length of stay. The independent variables were hospital
      setting (community, non-teaching hospitals, community, teaching hospitals, and
      academic medical centers) and tertiles of annual hospital diabetes delivery
      volume. Multivariable regression analysis was used to assess the relation of
      hospital setting with each outcome, adjusting for hospital volume and maternal
      case mix. RESULTS: 5,507 deliveries with type 2 (15%) and gestational (85%)
      diabetes were analyzed. Primary cesarean delivery rates among women with any
      diabetes did not vary across settings. After adjustment for volume and patient
      case mix, the likelihood of severe maternal morbidity was higher among deliveries
      at academic centers compared to community, non-teaching hospitals (odds ratio
      [OR], 2.1; 95% confidence interval: 1.0, 4.2). Academic centers had a protective
      effect (OR, 0.3; 95% CI: 0.2, 0.7) and community teaching hospitals had a
      borderline protective effect (OR, 0.8; 95% CI: 0.7, 1.0) on episiotomy, compared
      to community, non-teaching hospitals. Length of stay was greater at academic
      centers and community, teaching hospitals compared to community, non-teaching
      hospitals (5.4 days, 3.5 days vs. 2.8 days, respectively). We did not identify an
      independent association between hospital diabetes volume and clinical outcomes
      after adjustment for case mix. CONCLUSIONS: Among women with type 2 and
      gestational diabetes, hospital setting is associated with a higher likelihood of
      severe maternal morbidity and length of stay, independent of volume. Patient case
      mix accounts for some of the variation across settings. The volume-outcome
      relationship found with other complex medical conditions or procedures was not
      found among diabetic pregnancies. Further investigations are needed to explain
      variations in outcomes across hospital settings and volumes.

PMID- 19764844
TI  - Challenges presenting in transference and countertransference in the
      psychodynamic psychotherapy of a military service member.
AB  - Complicating the management of the transference-countertransference set for the
      military psychiatrist is the dilemma of dual agency. This can be a hidden force
      in the work of most psychiatrists but it is continuous in the field of military
      health care. The military clinician must candidly engage with this dilemma as it
      is intrinsic to the mission, "to conserve the fighting strength." In the conduct
      of a dynamic psychotherapy, the military psychiatrist must craft ways
      simultaneously to attain both the needs and interests of the individual patient
      and those of the organization of which he or she is a member. Presented in this
      article is a case in which the dual agency dilemma manifested itself between the
      patient and military therapist within the transference-countertransference set.
      The discussion will center around (a) how this ubiquitous dilemma may present and
      affect the progress of a psychotherapy, and (b) interventions that will help
      resolve the conflict. Time honored psychoanalytic principles guiding these
      interventions include maintenance of therapeutic neutrality, recognition of the
      therapist's bright and blind spots, and awareness of patterns in the patient's
      current and past relationships.

PMID- 19764845
TI  - The transforming power of ritual.
AB  - The dreams of a patient with chronic PTSD suggested that she was engaged in an
      unconscious search for a ritual to address one of her traumas. As dream analysis
      proceeded, the ritual was imagined, thought through, and planned jointly by
      therapist and patient, and eventually it was performed by the patient outside of
      the treatment setting. The positive effect of the ritual on working through of
      the trauma became evident in subsequent dreams and in a significant reduction of
      overt symptoms. Anthropological and psychological views of ritual, particularly
      concepts related to the numinous aspect of these activities, provide a context
      for the therapeutic intervention.

PMID- 19764846
TI  - Whose termination is it anyway?
AB  - Termination of psychoanalytic treatment presents a complex challenge concerning
      the application of psychoanalytic theory and technique. The paucity of cases that
      might provide analysts an opportunity to explore a variety of management
      approaches demands that practitioners share their experiences in as much detail
      as possible, but this occurs infrequently outside of seminars and discussion
      groups. In an effort to "cast a lens" on the termination process, a detailed
      description and process notes are presented from the closing phase of a 4-year
      analysis of a man with obsessive compulsive personality and difficulties with
      urination outside his home. The analyst's countertransference is emphasized,
      especially during enactments characteristic of this period. Alterations and
      variations in analytic technique and the demands for practical courses of action
      within and outside of the treatment are also examined. The issue of "forced"
      versus "natural" terminations is addressed as a means toward understanding a
      model of termination as a necessarily co-constructed component of analysis
      generally.

PMID- 19764847
TI  - The repetition compulsion in psychodynamic psychotherapy.
AB  - The repetition compulsion-the propensity to repeat formative early life
      experiences, for good or ill-is one of psychoanalysis's most important
      contributions to the understanding of human nature. However, its broader
      applications to psychodynamic psychiatry and psychotherapy have received little
      attention. In fact, it is a concept widely applicable to the understanding and
      treatment of psychiatric disorders, since maladaptive or self-defeating
      repetitions are the stuff of psychopathology. This article will discuss the
      repetition compulsion as a core concept of psychodynamic psychiatry. Principles
      of the compulsion to repeat will be applied to the dynamics of personality
      disorders, and will be illustrated by discussion of its usefulness in
      understanding and treating several common and representative psychiatric
      conditions: reactive depression, punitive superego function, and traumatic
      neurosis. These conditions illustrate the reparative, retributive, and
      restorative functions of the compulsion to repeat.

PMID- 19764848
TI  - The interaction of existential concerns and psychoanalytic insights in the
      treatment of contemporary patients.
AB  - Middle-aged and elderly patients have been shown to respond to psychoanalytic
      treatment, but they present certain characteristic problems not typical of young
      patients. I discuss these and offer a brief case presentation followed by a
      general discussion of the role of existential concerns and of their intertwining
      with psychoanalytic insights and interpretations in the treatment of older
      patients from our contemporary culture. The particular case of a relatively mild
      narcissistic personality disorder is used as an example of the kinds of
      difficulties contemporary psychoanalysts and psychodynamic psychiatrists run into
      in the current treatment of the aging patient population. The analyst's beliefs
      and personality are seen as more important than in classical Freudian
      psychoanalysis, and deliberate attention to the patient's existential concerns
      and cultural milieu cannot be avoided. A great deal of correction of what Gedo
      called "apraxias" is necessary, but I argue that in this situation each person
      must develop one's self in one's own way and without education and intrusion by
      the analyst. This self development in the face of one's inevitable future is seen
      as a vital aspect of contemporary psychoanalytic treatment of aging patients,
      regardless of which of the five orientation channels (that I have discussed
      elsewhere) are employed. The patient is seen as dealing both with his or her own
      infantile neurosis that is interfering with adult functioning and at the same
      time with universal existential human problems that become increasingly pressing
      as one ages. I contend that the current biological orientation of psychiatry is
      insufficient to address these difficulties, regardless of what advances we make
      in psychopharmacology and neurobiology. An exclusive neurobiological orientation
      can represent what existentialists label an "inauthentic choice" and a retreat
      from the spirit of humanism.

PMID- 19764849
TI  - The challenges of treating developmental trauma disorder in a residential agency
      for youth.
AB  - In recent years the task of psychiatrists serving youth in residential programs
      has largely shifted to rendering diagnostic evaluations and prescribing
      medications. Children in residential facilities are often misdiagnosed and
      treated with high doses of multiple medications drawn from several different
      classes of psychopharmaceuticals. The more accurate diagnosis for many of these
      children, Developmental Trauma Disorder (DTD), reconceptualizes the treatment
      approach and leads to substantial clinical benefit. Initiating treatment through
      application of milieu and dynamic psychotherapy and the tapering of medication
      very likely will encounter the challenges of staff resistance and the
      modification of the residence's institutional culture. The number of children
      receiving medication, the amount and number of medications used, and the number
      of aggressive incident reports fell dramatically over a 2-year period. Regarding
      mood and conduct disorders as manifestations of past trauma, rather than as
      biochemical imbalances, is the dominant focus of an analytically-informed
      treatment of DTD.

PMID- 19764850
TI  - A view from Riggs: treatment resistance and patient authority-XI. An alliance
      based intervention for suicide.
AB  - Treatment resistance has emerged as a significant issue, with evidence of a high
      risk of suicide in this population. This article reviews the history of the
      concept of the therapeutic alliance, argues for its central importance in work
      with suicidal and self-destructive patients, and introduces ABIS, an Alliance
      Based Intervention for Suicide that is carried out as part of psychodynamic
      psychotherapy. Principles of ABIS are delineated and explained.

PMID- 19764855
TI  - Sexual activity: an exercise to prevent cardiovascular morbidity and mortality?

PMID- 19764857
TI  - Primary prevention of vascular events in patients with high levels of C-reactive
      protein: the JUPITER study.
AB  - The Justification for the Use of Statins in Primary Prevention: An Intervention
      Trial Evaluating Rosuvastatin (JUPITER) study was the first large-scale,
      prospective study to examine the benefits of statin therapy in subjects with
      elevated levels of high-sensitivity C-reactive protein but with low-to-normal LDL
      cholesterol levels, who were not qualified for lipid-lowering treatment according
      to the current guidelines for primary prevention. The JUPITER study aimed to
      determine whether rosuvastatin 20 mg daily would reduce the rate of first major
      cardiovascular events, including cardiovascular death, nonfatal stroke, nonfatal
      myocardial infarction, hospitalization for unstable angina or arterial
      revascularization. Rosuvastatin reduced LDL-cholesterol levels by 50% and high
      sensitivity C-reactive protein by 37%. Compared with placebo, the combined
      primary end point was reduced in 44% (p < 0.00001), and total mortality in 20% (p
      = 0.02). The trial confirmed the relationship between the rates of major
      cardiovascular events with both high-sensitivity C-reactive protein and LDL
      cholesterol levels achieved after statin treatment. Interestingly, this was the
      first large, prospective statin trial to show benefit in the reduction of venous
      thromboembolism.

PMID- 19764858
TI  - The Vytorin on Carotid-Media Thickness and Overall Arterial Rigidity (VYCTOR)
      study.
AB  - Evaluation of: Meaney A, Ceballos G, Asbun J et al. The Vytorin on Carotid Intima
      Media Thickness and Overall Arterial Rigidity (VYCTOR) Study. J. Clin. Pharmacol.
      49(7), 838-847 (2009). The Vytorin on Carotid-Media Thickness and Overall
      Arterial Rigidity (VYCTOR) study was designed to assess the clinical effect of
      three lipid-lowering treatment regimens on carotid intima-media thickness. The
      study was designed to analyze 90 high-risk patients who were initially randomly
      allocated to three treatment groups; pravastatin 40 mg/day (group A), simvastatin
      40 mg/day (group B), and simvastatin 20 mg/day plus ezetimibe 10 mg/day (group C)
      as initial therapy. The therapeutic goals were less than 100 mg/dl LDL
      cholesterol in subjects with coronary disease or less than 70 mg/dl in high-risk
      subjects. Titration of the pharmacologic doses was allowed if therapeutic goals
      were not achieved. Subjects randomized to receive pravastatin (group A) were
      allowed to add 10 mg of ezetimibe to the baseline therapy. Patients in group B
      were titrated to 80 mg of simvastatin. Group C received simvastatin 40 mg/day and
      ezetimibe 10 mg/day. The primary end point of the trial was pharmacologic
      alteration of intima-media thickness over a 12-month trial period. Several
      secondary end points were also analyzed, including changes in LDL-cholesterol and
      high-sensitivity C-reactive protein. Additionally, alteration of arterial
      stiffness was also analyzed. Significant reductions in carotid intimal thickness
      and LDL-cholesterol levels (60%) were acheived with aggressive lipid-lowering
      therapy. The VYCTOR study did not reveal significant differences in C-reactive
      protein, HDL, triglycerides, blood pressure or BMI between groups.

PMID- 19764859
TI  - Use of stress testing prior to percutaneous coronary intervention in patients
      with stable coronary artery disease.
AB  - The majority of percutaneous coronary interventions (PCIs) are carried out in
      nonurgent situations, primarily in patients with stable coronary artery disease.
      Recent trials have concluded that for patients with stable coronary artery
      disease, treatment with optimal medical therapy versus optimal medical therapy
      plus PCI yields equivalent outcomes in terms of morbidity and future risk of
      myocardial infarction. Since PCI is a procedure with risk, it is important to
      identify patients for whom the benefit of the procedure outweighs the harms. PCI
      may be beneficial in certain subgroups, such as patients with moderate-to-severe
      ischemia on noninvasive testing. Although current guidelines require
      documentation of ischemia prior to elective PCI and this strategy is cost
      effective, pre-PCI stress testing appears to be underutilized, potentially
      leading to PCI being performed in patients who may not derive benefit from the
      procedure.

PMID- 19764860
TI  - The future is here: ventricular assist devices for the failing heart.
AB  - Mechanical circulatory support is an important adjunct to the management of
      patients with advanced heart failure. Technological advances in this area have
      improved overall survival and decreased the incidence of complications. In
      addition, they have expanded the population suitable for this therapy. The
      challenge for clinicians is to translate the clinical evidence into the selection
      of the most appropriate device that will benefit an individual patient. This
      paper will review ventricular assist devices currently available and their
      clinical indications.

PMID- 19764861
TI  - Vascular biology of eicosanoids and atherogenesis.
AB  - Atherosclerosis is a chronic and progressive inflammatory vascular disease that
      is characterized by a complex interplay between some components of the
      bloodstream and the arterial wall. The lipid derivatives eicosanoids have been
      identified as important mediators that contribute to mechanisms of atherogenesis.
      Prostaglandins and thromboxane A2 are members of the eicosanoid family
      synthesized from arachidonic acid by the combined action of cyclooxygenases and
      prostaglandins and thromboxane A2 synthase. Thromboxane A2, a potent platelet
      activator and vasoconstrictor and prostacyclin, a platelet inhibitor and
      vasodilator, are the most important in the development of cardiovascular
      diseases. Several pro-atherogenic biological effects have also been attributed to
      isoprostanes, a class of eicosanoid isomers formed via a free radical-mediated
      oxidation of fatty acids esterified in membrane phospholipids. Both groups of
      lipids manifest their biological activities by binding to specific receptors in
      target cells. In this article, we will describe the biological roles of
      prostacyclin, thromboxane A2 and isoprostanes in atherogenesis and discuss the
      latest pharmacological studies assessing the therapeutic effects of drugs that
      specifically target their biosynthesis and/or biological activities on vascular
      inflammation and atherosclerotic lesion development.

PMID- 19764862
TI  - Ablation strategies for atrial fibrillation.
AB  - Atrial fibrillation remains the most common arrhythmia in the USA and is
      associated with an increased risk for stroke, congestive heart failure and
      overall mortality. There has been a tremendous advance in the field of catheter
      ablation of atrial fibrillation that has resulted in better outcomes for
      patients. The approach for ablation of atrial fibrillation can be different
      depending on patients' presentation of paroxysmal or persistent atrial
      fibrillation. Pulmonary vein isolation remains the cornerstone of any ablation
      strategy for atrial fibrillation; however, further ablation, end points of the
      procedure, clinical end points for successful ablation and appropriate follow-up
      remain controversial. We aim to discuss these different approaches and the major
      controversies in catheter ablation of atrial fibrillation.

PMID- 19764863
TI  - Secondary prevention of stroke.
AB  - Stroke and transient ischemic attacks result from a range of mechanisms.
      Secondary prevention includes both conventional approaches to vascular risk
      factor management (blood pressure lowering, cholesterol reduction with statins,
      smoking cessation and antiplatelet therapy) and more specific interventions, such
      as carotid endarterectomy or anticoagulation for atrial fibrillation. The
      relative importance of even conventional risk factors in stroke differs from
      coronary artery disease. Large clinical trials produce information on most
      aspects of stroke prevention. Stroke and transient ischemic attacks are now
      recognized as medical emergencies, with a high early risk of recurrence, and
      evidence is accumulating to support the importance of immediate institution of
      secondary preventative treatments. We review current literature on the secondary
      prevention of stroke.

PMID- 19764864
TI  - Opportunities in pulmonary valve replacement.
AB  - Pulmonary regurgitation is the most important residual lesion after initial
      surgical correction for pulmonary (sub)valvular stenosis in the early life of
      patients with tetralogy of Fallot or isolated pulmonary stenosis. Symptomatic or
      asymptomatic patients with severe right ventricular dilatation due to pulmonary
      regurgitation may benefit from pulmonary valve replacement. Surgery is ideally
      performed before the right ventricle becomes irreversibly damaged as a result of
      longstanding volume overload. However, the beneficial effects must be weighed up
      against the problems associated with degradation of the allograft, which often
      result in (numerous) reoperations. Owing to the higher risk of thromboembolic
      events in mechanical prosthesis and the lifetime need for anticoagulation,
      allografts are the most widely used prosthesis. Degradation of the allograft
      often leads to reoperation, mostly 10-20 years after initial implantation. For a
      patient receiving his first allograft at 20 years of age, several reoperations
      will have to be performed later in life. Percutaneous pulmonary valve
      implantation has the potential to decrease the number of surgical reoperations.

PMID- 19764865
TI  - Depression and the cardiovascular system: increasing evidence of a link and
      therapeutic implications.
AB  - This review explores the epidemiological evidence for the relationship between
      depression and cardiovascular disease from a mechanistic standpoint. It is
      important to examine the biological, behavioral and social mechanisms to improve
      outcomes for depressed cardiac patients. A number of plausible biobehavioral
      mechanisms linking depression and cardiovascular disease have been identified.
      Tricyclic antidepressants have various effects on the cardiovascular system,
      while selective serotonin reuptake inhibitors are not associated with adverse
      cardiac effects and should, therefore, be the preferred choice for the treatment
      of most patients with comorbid depression and cardiovascular disease.

PMID- 19764866
TI  - Spectrum of pericardial disease: part I.
AB  - Pericardial disease is a common disorder seen in varying clinical settings and
      may be the first manifestation of an underlying systemic disease. It may be due
      to multiple causes. Epidemiologic studies are lacking, and the exact incidence
      and prevalence are unknown. New diagnostic techniques have improved diagnosis,
      allowing early diagnosis and management. There are few randomized data to guide
      physicians in the management of pericardial diseases. Part I of our review
      focuses on the current state of knowledge and management of the more common
      pericardial diseases: acute pericarditis, pericardial effusion, cardiac
      tamponade, chronic pericarditis and relapsing pericarditis.

PMID- 19764867
TI  - Spectrum of pericardial disease: part II.
AB  - Pericardial disease is a common disorder seen in varying clinical settings, and
      may be the first manifestation of an underlying systemic disease. In part I, we
      focused on the current knowledge and management of the more common pericardial
      diseases: acute pericarditis, pericardial effusion, cardiac tamponade, chronic
      pericarditis and relapsing pericarditis. In part II, we will focus on the
      knowledge and management of pericardial involvement in chylous pericardial
      effusion cholesterol pericarditis, radiation pericarditis, pericardial
      involvement in systemic inflammatory diseases, autoreactive pericarditis,
      pericarditis in renal failure, pericardial constriction and effusive constrictive
      pericarditis.

PMID- 19764869
TI  - Mean, variance, and autocorrelation of subthreshold potential fluctuations driven
      by filtered conductance shot noise.
AB  - We study the subthreshold voltage fluctuations of a conductance-based passive
      point neuron stimulated by filtered Poissonian shot noise. We give exact
      analytical expressions in terms of quadratures for the first two time-dependent
      moments and the autocorrelation function of the membrane voltage. We also derive
      simplified expressions for the moments in terms of elementary functions that hold
      true in the limit case of short filter time, small spike amplitude, and a single
      synaptic reversal potential. By means of these expressions, we show that for an
      ensemble of equilibrated conductances but sharp initial voltage (corresponding to
      a short voltage clamp at the initial time), the mean and the standard deviation
      can display nonmonotonic time courses. In particular, transient changes in the
      standard deviation disagree strongly with the predictions of the commonly used
      effective time constant approximation over a large parameter range. We also study
      the dependence of the correlation time of the voltage on the synaptic spike
      amplitude and the synaptic input rate. All results are confirmed by extensive
      stochastic simulations.

PMID- 19764870
TI  - Discrete states of synaptic strength in a stochastic model of spike-timing
      dependent plasticity.
AB  - A stochastic model of spike-timing-dependent plasticity (STDP) postulates that
      single synapses presented with a single spike pair exhibit all-or-none quantal
      jumps in synaptic strength. The amplitudes of the jumps are independent of
      spiking timing, but their probabilities do depend on spiking timing. By making
      the amplitudes of both upward and downward transitions equal, synapses then
      occupy only a discrete set of states of synaptic strength. We explore the impact
      of a finite, discrete set of strength states on our model, finding three
      principal results. First, a finite set of strength states limits the capacity of
      a single synapse to express the standard, exponential STDP curve. We derive the
      expression for the expected change in synaptic strength in response to a
      standard, experimental spike pair protocol, finding a deviation from exponential
      behavior. We fit our prediction to recent data from single dendritic spine heads,
      finding results that are somewhat better than exponential fits. Second, we show
      that the fixed-point dynamics of our model regulate the upward and downward
      transition probabilities so that these are on average equal, leading to a uniform
      distribution of synaptic strength states. However, third, under long-term
      potentiation (LTP) and long-term depression (LTD) protocols, these probabilities
      are unequal, skewing the distribution away from uniformity. If the number of
      states of strength is at least of order 10, then we find that three effective
      states of synaptic strength appear, consistent with some experimental data on
      ternary-strength synapses. On this view, LTP and LTD protocols may therefore be
      saturating protocols.

PMID- 19764871
TI  - Decoding movement trajectories through a T-maze using point process filters
      applied to place field data from rat hippocampal region CA1.
AB  - Firing activity from neural ensembles in rat hippocampus has been previously used
      to determine an animal's position in an open environment and separately to
      predict future behavioral decisions. However, a unified statistical procedure to
      combine information about position and behavior in environments with complex
      topological features from ensemble hippocampal activity has yet to be described.
      Here we present a two-stage computational framework that uses point process
      filters to simultaneously estimate the animal's location and predict future
      behavior from ensemble neural spiking activity. First, in the encoding stage, we
      linearized a two-dimensional T-maze, and used spline-based generalized linear
      models to characterize the place-field structure of different neurons. All of
      these neurons displayed highly specific position-dependent firing, which
      frequently had several peaks at multiple locations along the maze. When the rat
      was at the stem of the T-maze, the firing activity of several of these neurons
      also varied significantly as a function of the direction it would turn at the
      decision point, as detected by ANOVA. Second, in the decoding stage, we developed
      a state-space model for the animal's movement along a T-maze and used point
      process filters to accurately reconstruct both the location of the animal and the
      probability of the next decision. The filter yielded exact full posterior
      densities that were highly nongaussian and often multimodal. Our computational
      framework provides a reliable approach for characterizing and extracting
      information from ensembles of neurons with spatially specific context or task
      dependent firing activity.

PMID- 19764872
TI  - Estimation of sparse nonnegative sources from noisy overcomplete mixtures using
      MAP.
AB  - In this letter, we propose a new algorithm for estimating sparse nonnegative
      sources from a set of noisy linear mixtures. In particular, we consider difficult
      situations with high noise levels and more sources than sensors (underdetermined
      case). We show that when sources are very sparse in time and overlapped at some
      locations, they can be recovered even with very low signal-to-noise ratio, and by
      using many fewer sensors than sources. A theoretical analysis based on Bayesian
      estimation tools is included showing strong connections with algorithms in
      related areas of research such as ICA, NMF, FOCUSS, and sparse representation of
      data with overcomplete dictionaries. Our algorithm uses a Bayesian approach by
      modeling sparse signals through mixed-state random variables. This new model for
      priors imposes l(0) norm-based sparsity. We start our analysis for the case of
      nonoverlapped sources (1-sparse), which allows us to simplify the search of the
      posterior maximum avoiding a combinatorial search. General algorithms for
      overlapped cases, such as 2-sparse and k-sparse sources, are derived by using the
      algorithm for 1-sparse signals recursively. Additionally, a combination of our
      MAP algorithm with the NN-KSVD algorithm is proposed for estimating the mixing
      matrix and the sources simultaneously in a real blind fashion. A complete set of
      simulation results is included showing the performance of our algorithm.

PMID- 19764873
TI  - Plasticity-induced symmetry relationships between adjacent self-organizing
      topographic maps.
AB  - In many species, adjacent topographic maps in sensory neocortex are found to be
      oriented as roughly mirror-image copies of one another. Here we use a
      computational model to show for the first time that, in principle, adjacent
      cortical topographic maps that are mirror-image symmetric along two dimensions
      can arise from activity-dependent changes if the distribution radius of afferents
      sufficiently exceeds that of horizontal intracortical interactions. We also find
      that infrequently, other types of intermap symmetry and previously unexpected map
      relationships (such as interlocking rotation, in which two adjacent maps become
      intertwined) can occur. These results support the hypothesis that activity
      dependent synaptic changes play a more important role in forming the orientations
      of adjacent cortical maps than is currently recognized.

PMID- 19764874
TI  - Visuotactile representation of peripersonal space: a neural network study.
AB  - Neurophysiological and behavioral studies suggest that the peripersonal space is
      represented in a multisensory fashion by integrating stimuli of different
      modalities. We developed a neural network to simulate the visual-tactile
      representation of the peripersonal space around the right and left hands. The
      model is composed of two networks (one per hemisphere), each with three areas of
      neurons: two are unimodal (visual and tactile) and communicate by synaptic
      connections with a third downstream multimodal (visual-tactile) area. The
      hemispheres are interconnected by inhibitory synapses. We applied a combination
      of analytic and computer simulation techniques. The analytic approach requires
      some simplifying assumptions and approximations (linearization and a reduced
      number of neurons) and is used to investigate network stability as a function of
      parameter values, providing some emergent properties. These are then tested and
      extended by computer simulations of a more complex nonlinear network that does
      not rely on the previous simplifications. With basal parameter values, the
      extended network reproduces several in vivo phenomena: multisensory coding of
      peripersonal space, reinforcement of unisensory perception by multimodal
      stimulation, and coexistence of simultaneous right- and left-hand representations
      in bilateral stimulation. By reducing the strength of the synapses from the right
      tactile neurons, the network is able to mimic the responses characteristic of
      right-brain-damaged patients with left tactile extinction: perception of
      unilateral left tactile stimulation, cross-modal extinction and cross-modal
      facilitation in bilateral stimulation. Finally, a variety of sensitivity analyses
      on some key parameters was performed to shed light on the contribution of single
      model components in network behaviour. The model may help us understand the
      neural circuitry underlying peripersonal space representation and identify its
      alterations explaining neurological deficits. In perspective, it could help in
      interpreting results of psychophysical and behavioral trials and clarifying the
      neural correlates of multisensory-based rehabilitation procedures.

PMID- 19764875
TI  - Adaptive relevance matrices in learning vector quantization.
AB  - We propose a new matrix learning scheme to extend relevance learning vector
      quantization (RLVQ), an efficient prototype-based classification algorithm,
      toward a general adaptive metric. By introducing a full matrix of relevance
      factors in the distance measure, correlations between different features and
      their importance for the classification scheme can be taken into account and
      automated, and general metric adaptation takes place during training. In
      comparison to the weighted Euclidean metric used in RLVQ and its variations, a
      full matrix is more powerful to represent the internal structure of the data
      appropriately. Large margin generalization bounds can be transferred to this
      case, leading to bounds that are independent of the input dimensionality. This
      also holds for local metrics attached to each prototype, which corresponds to
      piecewise quadratic decision boundaries. The algorithm is tested in comparison to
      alternative learning vector quantization schemes using an artificial data set, a
      benchmark multiclass problem from the UCI repository, and a problem from
      bioinformatics, the recognition of splice sites for C. elegans.

PMID- 19764876
TI  - Current source density reconstruction from incomplete data.
AB  - We propose two ways of estimating current source density (CSD) from measurements
      of voltage on a Cartesian grid with missing recording points using the inverse
      CSD method. The simplest approach is to substitute local averages (LA) in place
      of missing data. A more elaborate alternative is to estimate a smaller number of
      CSD parameters than the actual number of recordings and to take the least-squares
      fit (LS). We compare the two approaches in the three-dimensional case on several
      sets of surrogate and experimental data, for varying numbers of missing data
      points, and discuss their advantages and drawbacks. One can construct CSD
      distributions for which one or the other approach is better. However, in general,
      the LA method is to be recommended as being more stable and more robust to
      variations in the recorded fields.

PMID- 19764877
TI  - Learning to discriminate through long-term changes of dynamical synaptic
      transmission.
AB  - Short-term synaptic plasticity is modulated by long-term synaptic changes. There
      is, however, no general agreement on the computational role of this interaction.
      Here, we derive a learning rule for the release probability and the maximal
      synaptic conductance in a circuit model with combined recurrent and feedforward
      connections that allows learning to discriminate among natural inputs. Short-term
      synaptic plasticity thereby provides a nonlinear expansion of the input space of
      a linear classifier, whereas the random recurrent network serves to decorrelate
      the expanded input space. Computer simulations reveal that the twofold increase
      in the number of input dimensions through short-term synaptic plasticity improves
      the performance of a standard perceptron up to 100%. The distributions of release
      probabilities and maximal synaptic conductances at the capacity limit strongly
      depend on the balance between excitation and inhibition. The model also suggests
      a new computational interpretation of spikes evoked by stimuli outside the
      classical receptive field. These neuronal activities may reflect decorrelation of
      the expanded stimulus space by intracortical synaptic connections.

PMID- 19764878
TI  - Asymptotic behavior of periodic Cohen-Grossberg neural networks with delays.
AB  - Without assuming the positivity of the amplification functions, we prove some M
      matrix criteria for the R(n)(+)-global asymptotic stability of periodic Cohen
      Grossberg neural networks with delays. By an extension of the Lyapunov method, we
      are able to include neural systems with multiple nonnegative periodic solutions
      and nonexponential convergence rate in our model and also include the Lotka
      Volterra system, an important prototype of competitive neural networks, as a
      special case. The stability criteria for autonomous systems then follow as a
      corollary. Two numerical examples are provided to show that the limiting
      equilibrium or periodic solution need not be positive.

PMID- 19764879
TI  - Hebbian self-organizing integrate-and-fire networks for data clustering.
AB  - We propose a Hebbian learning-based data clustering algorithm using spiking
      neurons. The algorithm is capable of distinguishing between clusters and noisy
      background data and finds an arbitrary number of clusters of arbitrary shape.
      These properties render the approach particularly useful for visual scene
      segmentation into arbitrarily shaped homogeneous regions. We present several
      application examples, and in order to highlight the advantages and the weaknesses
      of our method, we systematically compare the results with those from standard
      methods such as the k-means and Ward's linkage clustering. The analysis
      demonstrates that not only the clustering ability of the proposed algorithm is
      more powerful than those of the two concurrent methods, the time complexity of
      the method is also more modest than that of its generally used strongest
      competitor.

PMID- 19764880
TI  - The computational structure of spike trains.
AB  - Neurons perform computations, and convey the results of those computations
      through the statistical structure of their output spike trains. Here we present a
      practical method, grounded in the information-theoretic analysis of prediction,
      for inferring a minimal representation of that structure and for characterizing
      its complexity. Starting from spike trains, our approach finds their causal state
      models (CSMs), the minimal hidden Markov models or stochastic automata capable of
      generating statistically identical time series. We then use these CSMs to
      objectively quantify both the generalizable structure and the idiosyncratic
      randomness of the spike train. Specifically, we show that the expected
      algorithmic information content (the information needed to describe the spike
      train exactly) can be split into three parts describing (1) the time-invariant
      structure (complexity) of the minimal spike-generating process, which describes
      the spike train statistically; (2) the randomness (internal entropy rate) of the
      minimal spike-generating process; and (3) a residual pure noise term not
      described by the minimal spike-generating process. We use CSMs to approximate
      each of these quantities. The CSMs are inferred nonparametrically from the data,
      making only mild regularity assumptions, via the causal state splitting
      reconstruction algorithm. The methods presented here complement more traditional
      spike train analyses by describing not only spiking probability and spike train
      entropy, but also the complexity of a spike train's structure. We demonstrate our
      approach using both simulated spike trains and experimental data recorded in rat
      barrel cortex during vibrissa stimulation.

PMID- 19764881
TI  - Thioredoxin-binding protein-2 deficiency enhances methionine-choline deficient
      diet-induced hepatic steatosis but inhibits steatohepatitis in mice.
AB  - In nonalcoholic fatty liver disease, oxidative stress is believed to play a
      crucial role as a second-hit for the progression of simple steatosis to
      steatohepatitis. Thioredoxin (TRX) is a potent antioxidant molecule that exerts
      anti-apoptotic and anti-inflammatory functions. TRX-binding protein-2 (TBP-2) is
      an endogenous negative regulator of TRX. Deficiency of TBP-2 in mice causes
      hyperlipidemia, hepatic steatosis, hypoglycemia, and bleeding tendency,
      resembling Reye syndrome in a fasting/glucose-deficient state. The aim of this
      study was to investigate the role of TBP-2 in the development of nonalcoholic
      steatohepatitis (NASH). TBP-2-deficient (TBP-2(-/-)) and wild-type (WT) mice were
      fed either a normal or methionine-choline-deficient (MCD) diet for up to 10
      weeks. Compared with WT mice, TBP-2(-/-) mice showed severe simple steatosis
      rather than steatohepatitis. However, oxidative stress determined by lipid
      peroxidation and DNA damage, neutrophil infiltration, and hepatic fibrosis were
      attenuated in TBP-2(-/-) mice. PCR analysis showed the expressions of fibrosis
      inducing and inflammatory cytokine-related genes were less in TBP-2(-/-) mice.
      Moreover, leptin, SREBP1c, PPARgamma, and adipogenesis-lipogenesis-related genes
      were upregulated in TBP-2(-/-) mice. These results strongly suggested that TBP-2
      might be involved in pathogenesis of NASH in WT mice, and inhibitors of TBP-2
      could be useful in the prevention or treatment of NASH.

PMID- 19764882
TI  - ROS-dependent signaling mechanisms for hypoxic Ca(2+) responses in pulmonary
      artery myocytes.
AB  - Hypoxic exposure causes pulmonary vasoconstriction, which serves as a critical
      physiologic process that ensures regional alveolar ventilation and pulmonary
      perfusion in the lungs, but may become an essential pathologic factor leading to
      pulmonary hypertension. Although the molecular mechanisms underlying hypoxic
      pulmonary vasoconstriction and associated pulmonary hypertension are uncertain,
      increasing evidence indicates that hypoxia can result in a significant increase
      in intracellular reactive oxygen species concentration ([ROS](i)) through the
      mitochondrial electron-transport chain in pulmonary artery smooth muscle cells
      (PASMCs). The increased mitochondrial ROS subsequently activate protein kinase C
      epsilon (PKCepsilon) and NADPH oxidase (Nox), providing positive mechanisms that
      further increase [ROS](i). ROS may directly cause extracellular Ca(2+) influx by
      inhibiting voltage-dependent K(+) (K(V)) channels and opening of store-operated
      Ca(2+) (SOC) channels, as well as intracellular Ca(2+) release by activating
      ryanodine receptors (RyRs), leading to an increase in intracellular Ca(2+)
      concentration ([Ca(2+)](i)) and associated contraction. In concert with ROS,
      PKCepsilon may also affect K(V) channels, SOC channels, and RyRs, contributing to
      hypoxic Ca(2+) and contractile responses in PASMCs.

PMID- 19764883
TI  - Acute hepatitis C virus infection in young adult injection drug users: a
      prospective study of incident infection, resolution, and reinfection.
AB  - BACKGROUND: Hepatitis C virus (HCV) infection, clearance, and reinfection are
      best studied in injection drug users (IDUs), who have the highest incidence of
      HCV and are likely to represent most infections. METHODS: A prospective cohort of
      HCV-negative young IDUs was followed up from January 2000 to September 2007, to
      identify acute and incident HCV and prospectively study infection outcomes.
      RESULTS: Among 1,191 young IDUs screened, 731 (61.4%) were HCV negative, and 520
      (71.1%) of the 731 were enrolled into follow-up. Cumulative HCV incidence was
      26.7/100 person-years of observation (95% confidence interval [CI], 21.5-31.6).
      Of 135 acute/incident HCV infections, 95 (70.4%) were followed; 20 (21.1%) of the
      95 infections cleared. Women had a significantly higher incidence of viral
      clearance than did men (age-adjusted hazard ratio, 2.91 [95% CI, 1.68-5.03]) and
      also showed a faster rate of early HCV viremia decline (P < .01). The estimated
      reinfection rate was 24.6/100 person-years of observation (95% CI, 11.7-51.6).
      Among 7 individuals, multiple episodes of HCV reinfection and reclearance were
      observed. CONCLUSIONS: In this large sample of young IDUs, females show
      demonstrative differences in their rates of viral clearance and kinetics of early
      viral decline. Recurring reinfection and reclearance suggest possible protection
      against persistent infection. These results should inform HCV clinical care and
      vaccine development.

PMID- 19764884
TI  - Replication-deficient rabies virus-based vaccines are safe and immunogenic in
      mice and nonhuman primates.
AB  - Although current postexposure prophylaxis rabies virus (RV) vaccines are
      effective, approximately 40,000-70,000 rabies-related deaths are reported
      annually worldwide. The development of effective formulations requiring only 1-2
      applications would significantly reduce mortality. We assessed in mice and
      nonhuman primates the efficacy of replication-deficient RV vaccine vectors that
      lack either the matrix (M) or phosphoprotein (P) gene. A single dose of M gene
      deficient RV induced a more rapid and efficient anti-RV response than did P gene
      deficient RV immunization. Furthermore, the M gene-deleted RV vaccine induced 4
      fold higher virus-neutralizing antibody (VNA) levels in rhesus macaques than did
      a commercial vaccine within 10 days after inoculation, and at 180 days after
      immunization rhesus macaques remained healthy and had higher-avidity antibodies,
      higher VNA titers, and a more potent antibody response typical of a type 1 T
      helper response than did animals immunized with a commercial vaccine. The data
      presented in this article suggest that the M gene-deleted RV vaccine is safe and
      effective and holds the potential of replacing current pre- and postexposure RV
      vaccines.

PMID- 19764885
TI  - Molecular epidemiology of Mycobacterium tuberculosis in a South African community
      with high HIV prevalence.
AB  - To explore the relationship between human immunodeficiency virus (HIV) and
      Mycobacterium tuberculosis genotypes, we performed IS6110-based restriction
      fragment-length polymorphism analysis on M. tuberculosis culture specimens from
      patients with smear-positive tuberculosis in a periurban community in South
      Africa from 2001 through 2005. Among 151 isolates, 95 strains were identified
      within 26 families, with 54% clustering. HIV status was associated with W-Beijing
      strains (P = .009) but not with clustering per se. The high frequency of
      clustering suggests ongoing transmission in both HIV-negative and HIV-positive
      individuals in this community. The strong association between W-Beijing and HIV
      infection may have important implications for tuberculosis control.

PMID- 19764886
TI  - Signature nucleotide polymorphisms at positions 64 and 65 in reverse
      transcriptase favor the selection of the K65R resistance mutation in HIV-1
      subtype C.
AB  - Recently, we described a novel nucleotide template-based mechanism that may be
      the basis for the facilitated acquisition of the K65R resistance mutation in
      subtype C versus subtype B human immunodeficiency virus type 1 (HIV-1). In this
      article, we evaluated the effects of subtype C-specific silent polymorphisms in
      cell culture drug-selection experiments using nucleoside and nucleotide reverse
      transcriptase inhibitors. The K65R pathway was selected more frequently in a
      subtype B virus that contained subtype C nucleotide polymorphisms at both
      positions 64 and 65 than in a wild-type NL4-3 subtype B virus. This is the first
      demonstration of the significance of silent nucleotide polymorphisms in the
      development of drug resistance.

PMID- 19764887
TI  - Skin-derived stem cells in human scar tissues: a novel isolation and
      proliferation technique and their differentiation potential to neurogenic
      progenitor cells.
AB  - Adult tissues contain stem cells that can transdifferentiate into other cell
      lineages besides forming differentiated cells of their own tissue of origin.
      However, human adult skin-derived stem cells have a very low efficiency. Here we
      established a novel culture system involving bone morphogenetic protein-4 and a
      floating culture system with sphere-producing medium that can enrich adult stem
      cell populations in vitro. Adult stem cells were isolated from useless human scar
      tissue. Like mesenchymal stem cells, cultured human scar tissue-derived stem
      cells (hSTSCs) altered their morphology and significantly increased the number of
      Nestin-positive cells in proportion to the alkaline phosphatase-positive cell
      ratio. Moreover, the expression of the pluripotency regulator Oct-4 and its
      target transcripts, Sox-2, c-kit, and Rex-1, was also stimulated by this culture
      system. Differentiation of neurogenic progenitor cells using basic fibroblast
      growth factor and Neurogen 2 was successfully performed in vitro more rapidly
      than previous reports. Neuronal differentiation results showed that our hSTSCs
      expressed marker of neurogenic genes, such as glial fibrillary acid protein,
      neural cell adhesion molecules, neuron filament-M, and microtubule-associated
      protein 2. These results suggest that bone morphogenetic protein-4 and the
      floating culture system with sphere-producing medium induced significant
      proliferation of hSTSCs and mediated reprogramming of the cells from adult
      somatic tissue into precursor state to some degree. It is thought that this new
      culture system might be a simple, effective, and easily manageable process for
      regenerative tissue repair and autotransplantation.

PMID- 19764888
TI  - Comment and reply on: Serological response to tick-borne encephalitis (TBE)
      vaccination in the elderly--results from an observational study.

PMID- 19764889
TI  - Motavizumab for the prevention of respiratory syncytial virus infection in
      infants.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) is the most important respiratory
      viral pathogen of infancy. The only unequivocally effective pharmacological
      compound for the management of RSV infection is palivizumab, a monoclonal
      antibody against the fusion protein of RSV. Recently, motavizumab, a similar but
      more potent monoclonal antibody, has been developed and tested against
      palivizumab. OBJECTIVE: In this review, we summarize data comparing the safety
      and efficacy of the two monoclonal antibodies in prevention of RSV infection.
      Other therapeutic options also are discussed. METHODS: We reviewed all published
      articles listing motavizumab or palivizumab in the title or keywords.
      RESULTS/CONCLUSION: In a large comparative clinical trial for which peer review
      is pending, motavizumab proved noninferior to palivizumab for prevention of RSV
      related hospital admission in infants with underlying conditions placing them at
      high risk for hospitalization after RSV infection. In this trial, motavizumab in
      comparison to palivizumab significantly reduced the severity of illness among
      those infants hospitalized with RSV infection, as well as the number of
      outpatient lower respiratory infections caused by RSV. Safety profiles of each of
      the two compounds were excellent. Based on these data, motavizumab should
      eventually replace palivizumab in the prevention of RSV infection.

PMID- 19764890
TI  - Vilazodone, a novel dual-acting serotonergic antidepressant for managing major
      depression.
AB  - Major depressive disorder (MDD) affects <or= 15% of the general population and
      imparts a significant economic and psychosocial burden. Despite the availability
      of a wide range of drugs for treating MDD, the majority of patients fail to
      achieve complete and sustained remission of symptoms. Vilazodone is a novel dual
      acting serotonergic antidepressant currently in clinical development for the
      treatment of MDD. Vilazodone combines the effects of a selective serotonin
      reuptake inhibitor with 5-HT(1A) receptor partial agonist activity. In a recent
      Phase III clinical trial, vilazodone showed significant antidepressant efficacy
      compared to placebo with a statistically significant onset of effect at 1 week.
      Overall dropout rates were low. Diarrhea, nausea and headache were the most
      common adverse events reported. In addition, there was no significant difference
      between placebo and vilazodone in terms of sexual dysfunction as measured by the
      Arizona Sexual Experiences Scale. A unique feature of the vilazodone clinical
      program is the concurrent development of biomarkers that may predict treatment
      response and common side effects. Vilazodone offers a dual mechanism of action,
      good general tolerability with the potential for less impairment of sexual
      function than selective serotonin reuptake inhibitors and the possibility of
      personalized treatment for MDD.

PMID- 19764892
TI  - Role of type 3 deiodinase in cancer.
AB  - Thyroid hormone (TH) influences a wide variety of biological events in
      vertebrates. Among them, the balance between proliferation and differentiation is
      crucial in TH action in normal and pathological conditions, including cancer.
      Thyroid hormone signaling results from the interaction of T3 with nuclear
      receptors that, in concert with other transcription factors, stimulate or repress
      the expression of target genes, some of which are involved in the control of
      cellular proliferation. Ligand (T3) availability is under tight control at both
      extracellular and intracellular levels. Intracellular T3 concentrations are
      influenced by the action of selenodeiodinases. These enzymes can, within the
      single cell, enhance (D1 and D2) or reduce (D3) T3 concentrations, thereby
      constituting a potent mechanism of pre-receptoral control of TH action. Type 3
      deiodinase, the major physiological inactivator of TH, is highly expressed in
      developing tissues and in some tumoral tissues, with a mostly unknown function.
      Recent studies suggest that D3 enzyme plays an important role in the control of
      TH metabolism and action during tumorigenesis. In this review, we focus on D3 and
      its potential as a novel tumoral marker and new molecular target in cancer
      treatment.

PMID- 19764891
TI  - Targeting SGK1 in diabetes.
AB  - Compelling evidence is accumulating indicating a pathophysiological role of the
      serum-and-glucocorticoid-inducible-kinase-1 (SGK1) in the development and
      complications of diabetes. SGK1 is ubiquitously expressed with exquisitely high
      transcriptional volatility. Stimulators of SGK1 expression include hyperglycemia,
      cell shrinkage, ischemia, glucocorticoids and mineralocorticoids. SGK1 is
      activated by insulin and growth factors via PI3K, 3-phosphoinositide dependent
      kinase PDK1 and mTOR. SGK1 activates ion channels (including ENaC, TRPV5, ROMK,
      KCNE1/KCNQ1 and CLCKa/Barttin), carriers (including NCC, NKCC, NHE3, SGLT1 and
      EAAT3), and the Na(+)/K(+)-ATPase. It regulates the activity of several enzymes
      (e.g., glycogen-synthase-kinase-3, ubiquitin-ligase Nedd4-2, phosphomannose
      mutase-2), and transcription factors (e.g., forkhead-transcription-factor FOXO3a,
      beta-catenin and NF-kappaB). A common SGK1 gene variant ( approximately 3 - 5%
      prevalence in Caucasians, approximately 10% in Africans) is associated with
      increased blood pressure, obesity and type 2 diabetes. In patients suffering from
      type 2 diabetes, SGK1 presumably contributes to fluid retention and hypertension,
      enhanced coagulation and increased deposition of matrix proteins leading to
      tissue fibrosis such as diabetic nephropathy. Accordingly, targeting SGK1 may
      favourably influence occurrence and course of type 2 diabetes.

PMID- 19764893
TI  - Combination 830-nm and 633-nm light-emitting diode phototherapy shows promise in
      the treatment of recalcitrant psoriasis: preliminary findings.
AB  - BACKGROUND AND OBJECTIVES: Psoriasis is one of the major problems facing
      dermatologists worldwide. Planar arrays of light-emitting diodes (LEDs) have
      recently attracted attention in the treatment of difficult dermatological
      entities, 830 nm in near infrared (near-IR) and 633 nm in visible red. This study
      was designed to assess the efficacy of combination 830-nm and 633-nm LED
      phototherapy in the treatment of recalcitrant psoriasis. SUBJECTS AND METHODS:
      Nine informed and consenting patients with psoriasis were enrolled in this
      preliminary study, (3 men, 6 women, mean age 34.3, skin types I to IV). All had
      chronic psoriasis, which in most cases had proved resistant to conventional
      treatments. They were treated sequentially with LED arrays delivering continuous
      wave 830 nm (near-IR) and 633 nm (red) in two 20-min sessions over 4 or 5 weeks,
      with 48 h between sessions (830 nm, 60 J/cm(2); 633 nm, 126 J/cm(2)). RESULTS:
      All patients completed their LED regimens (4 requiring 1 regimen, 5 requiring a
      second). Follow-up periods were from 3 to 8 months, except in two patients who
      were lost to follow-up. Clearance rates at the end of the follow-up period ranged
      from 60% to 100%. Satisfaction was universally very high. CONCLUSIONS: The
      antiinflammatory effects of LED energy at 830 nm and 633 nm have been well
      documented, as has their use in wound healing. LED phototherapy is easy to apply,
      pain free and side-effect free, and is well tolerated by patients of all skin
      types. The promising results of this preliminary study warrant a proper
      controlled double-blind study with a larger patient population.

PMID- 19764894
TI  - Low-level laser irradiation (InGaAlP-660 nm) increases fibroblast cell
      proliferation and reduces cell death in a dose-dependent manner.
AB  - BACKGROUND AND OBJECTIVE: Impaired cell metabolism and increased cell death in
      fibroblast cells are physiological features of chronic tendinopathy. Although
      several studies have shown that low-level laser therapy (LLLT) at certain
      parameters has a biostimulatory effect on fibroblast cells, it remains uncertain
      if LLLT effects depend on the physiological state. STUDY DESIGN/MATERIAL AND
      METHODS: High-metabolic immortal cell culture and primary human keloid fibroblast
      cell culture were used in this study. Trypan blue exclusion and the 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test were used to
      determine cell viability and proliferation. Propidium iodide stain was used for
      cell-cycle analysis by flow cytometry. Laser irradiation was performed daily on
      three consecutive days with a GaAlAs 660-nm laser (mean output: 50 mW, spot size
      2 mm(2), power density =2.5 W/cm(2)) and a typical LLLT dose and a high LLLT dose
      (irradiation times: 60 or 420 s; fluences:150 or 1050 J/cm(2); energy delivered:
      3 or 21 J). RESULTS: Primary fibroblast cell culture from human keloids
      irradiated with 3 J showed significant proliferation by the trypan blue exclusion
      test (p < 0.05), whereas the 3T3 cell culture showed no difference using this
      method. Propidium iodide staining flow cytometry data showed a significant
      decrease in the percentage of cells being in proliferative phases of the cell
      cycle (S/g(2)/M) when irradiated with 21 J in both cell types (hypodiploid cells
      increased). CONCLUSIONS: Our data support the hypothesis that the physiological
      state of the cells affects the LLLT results, and that high-metabolic rate and
      short- cell-cycle 3T3 cells are not responsive to LLLT. In conclusion, LLLT with
      a dose of 3 J reduced cell death significantly, but did not stimulate cell cycle.
      A LLLT dose of 21 J had negative effects on the cells, as it increased cell death
      and inhibited cell proliferation.

PMID- 19764895
TI  - Effect of low-level laser therapy with output power of 30 mW and 60 mW in the
      viability of a random skin flap.
AB  - OBJECTIVE: To assess the effects of low-level laser therapy (LLLT) with output
      power of 30 and 60 mW in the viability of a random skin flap in rats. BACKGROUND
      DATA: Output power values in LLLT are not well defined. MATERIALS AND METHODS:
      Controlled, single-blind experimental study. Thirty-six animals were randomly
      distributed into three groups: sham group (SG), 30-mW output power (30G), and 60
      mW output power (60G). In both treated groups, a fluency of 3 J/cm(2) was used.
      Two minutes after elevation of a random-pattern cranially based dorsal flap (4 x
      10 cm), laser irradiation was applied and repeated on the first, second, third,
      and fourth postoperative days. Percentages of flap necrosis were calculated on
      the seventh postoperative day. Also, four fragments of each flap were collected
      to allow determination of the percentages of vascular density according to the
      bidimensional method of the morphometric analysis of blood vessels. Statistical
      analysis included the Wilcoxon test and Kruskal-Wallis variance analysis. A
      significance level of 5% was elected (p < 0.05). RESULTS: Laser-treated animals
      presented significantly less necrosis than the sham group (SG, 53%; 30G, 24%; p <
      0.05) (60G, 25%; p < 0.05). Also, laser-treated animals presented significantly
      more vascular density than the sham group (SG, 37%; 30G, 57%; p < 0.05) (60G,
      59%; p < 0.05). CONCLUSION: LLLT (660 nm) with 30-mW and 60-mW output power was
      efficient in the increase of skin flap viability, but there was no difference
      between them.

PMID- 19764896
TI  - Analysis of permeability and morphology of root canal dentin after Er,Cr:YSGG
      laser irradiation.
AB  - OBJECTIVE: The aim of this study was to evaluate the morphology and permeability
      of root canal walls irradiated with Er,Cr:YSGG laser after conventional
      endodontic treatment. BACKGROUND: Laser irradiation can be used for dentinal
      tubule exposure, smear layer removal, and disinfection. Another potential,
      interesting application is as an adjunct to endodontic treatment, especially in
      the intracanal medication phase. METHODS: Fifty-two single-rooted teeth had their
      crowns sectioned at the cementoenamel junction and were randomly divided into
      four groups (n = 13): G1: conventional preparation (CP) + irrigation with EDTA-T
      + rhodamine B dye solution associated with NDP (dexamethasone phosphate,
      paramonochlorophenol, polyethylenoglycol) (Rhod-NDP); G2: CP + EDTA-T +
      Er,Cr:YSGG laser irradiation 0.75 W + Rhod-NDP; G3: CP + EDTA-T + Er,Cr:YSGG 1.5
      W + Rhod-NDP; G4: CP + EDTA-T + Er,Cr:YSGG 2.5 W + Rhod-NDP. For the permeability
      analysis (n = 9), teeth were transversely cut and two slices of each third were
      selected. The images were analyzed by ImageLab software (Softium Informatica
      Ltda., Sao Paulo, SP, Brazil). Additional samples (n = 4) were examined by
      scanning electron microscopy. RESULTS: Data were analyzed statistically using the
      Kruskal-Wallis and Student-Newman-Keuls tests for the following areas: apical
      third (H = 23.4651): G1 (14.25)(a), G2 (17.66)(ab), G3 (26.50)(b), G4 (39.58)(c);
      medium (H = 23.1611): G1 (14.16)(a), G2 (16.66)(ab), G3 (28.83)(b), G4
      (38.33)(b); and cervical (H = 32.4810): G1 (9.66)(a), G2 (20. 00)(ab), G3
      (27.00)(b), G4 (41.33)(c), (p < 0.01). Despite the irregular aspect of laser
      irradiation along the canal walls, the parameters of 1.5 W and 2.5 W allowed
      morphologic modifications that increased dentinal permeability. CONCLUSIONS:
      Irradiation with Er,Cr:YSGG laser could be effective in endodontic treatment for
      increasing dentinal permeability.

PMID- 19764897
TI  - Highlight: 'regenerative hepatology'.

PMID- 19764898
TI  - Laser therapy in the tissue repair process: a literature review.
AB  - OBJECTIVE: Carry out a literature review on the use of laser therapy in the
      tissue repair process and address the different lasers and parameters used by the
      authors. METHODS: A review was carried out of the literature from 1960 to 2008 in
      the Lilacs, Medline, and PubMed databases using the following key words: Laser
      Therapy, Wound Healing, and Tissue repair. RESULTS: The most frequently used
      types of laser are helium neon (HeNe) lasers and diode lasers, including gallium
      aluminum-arsenium (GaAlAs), arsenium-gallium (AsGa), and indium-gallium-aluminum
      phosphide (InGaAlP) lasers. However, implementation of different protocols was
      found, with different materials and different activating wavelengths, thus making
      it difficult to compare results and choose the parameters of treatment.
      CONCLUSIONS: The majority of authors report that laser therapy speeds up the
      process of tissue repair, but further studies are suggested to determine the best
      parameters to be used.

PMID- 19764899
TI  - Use of 660-nm diode laser in the prevention and treatment of human oral mucositis
      induced by radiotherapy and chemotherapy.
AB  - OBJECTIVE: The aim of this multidisciplinary study was to evaluate quantitatively
      and qualitatively the effect of a 660-nm diode laser in the prevention and
      treatment of human oral mucositis (OM) in patients suffering from head and neck
      cancer who had undergone radiotherapy and chemotherapy. BACKGROUND DATA: OM is a
      severe oral lesion resulting from the toxic effects of treatment for cancer in
      the head and neck region. Low-level laser therapy is indicated to prevent and
      treat this oral complication and may be used alone or in association with
      conventional drug treatment, producing pain relief and wound repair. METHODS:
      This study included 72 patients with head and neck cancer treated at the Cancer
      Hospital of Mato-Grosso, Brazil, and divided into a control group (C; n = 36) and
      a laser group (L; n = 36). Laser therapy was performed in combination with
      radiotherapy and chemotherapy twice a week using a diode laser (lambda = 660 nm,
      power = 30 mW, spot size = 2 mm, energy = 2 J per point). RESULTS: Statistically
      significant differences were observed between the two groups. Patients in group L
      usually did not present with OM or pain, but all patients in group C presented
      with OM ranging from Level I to III associated with pain. This difference was
      significant from week 1 on, increased until week 4 and remained stable up to week
      7. CONCLUSION: Laser therapy was effective in preventing and treating oral
      effects induced by radiotherapy and chemotherapy, thus improving the patient's
      quality of life.

PMID- 19764900
TI  - The effect of irradiance level in 980-nm diode laser skin welding.
AB  - OBJECTIVE: Current research aimed to investigate the role of irradiance in skin
      laser welding. BACKGROUND DATA: Optical and thermal responses of tissue to
      infrared irradiation are highly dependent on both wavelength and tissue type. The
      desired effect on tissue is created by proper selection of laser power,
      application time, and spot size. METHODS: Full-thickness skin incisions on Wistar
      rat dorsum were welded with 980-nm diode laser application. Two irradiance levels
      (200 and 16.6 W/cm(2)) were applied with high (6 W, 400 ms) and low (0.5 W, 5 s)
      powers of laser with the same spot size (0.03 cm(2)). Subjects were monitored
      throughout a 21-day recovery period; incisions were sampled for histology and
      mechanical tests on particular control days (1, 4, 7, 14, and 21). Closure index,
      thermally altered areas, epidermal thickness, and granulation areas of H&E
      (eosin) stained samples were calculated. The breaking point during a mechanical
      tensile test that ran at 5-mm/min crosshead speed was recorded. RESULTS: In the
      suture group, there was no closure 24 h postoperation. For laser groups,
      immediate closure at the surface layers of the incisions was observed: Almost
      half-thickness (from surface to deep dermis) welding was achieved. Granulation
      tissue level and epidermal thickness level for all groups were similar on
      postoperative day 21. CONCLUSION: The laser welding technique was found reliable
      in terms of immediate and mechanically strong closure compared with suture. Low
      irradiance of a 980-nm laser (16.6 W/cm(2)) yielded noticeably stronger bonds at
      the end of 21 days of recovery, as well as minimal thermal damage.

PMID- 19764901
TI  - Secretory phospholipase A2 promotes MMP-9-mediated cell death by degrading type I
      collagen via the ERK pathway at an early stage of chondrogenesis.
AB  - BACKGROUND INFORMATION: sPLA2 (secretory phospholipase A2) has been implicated in
      a wide range of cellular responses, including cell proliferation and ECM
      (extracellular matrix) remodelling. Even though ECM remodelling is an essential
      step for chondrogenesis, the expression and functions of sPLA2 during
      chondrogenesis have not been studied. RESULTS: In the present study, for the
      first time, we detect the secretion of sPLA2 during limb development and suggest
      that sPLA2 influences the proliferation and/or survival of limb mesenchymal
      cells. Treatment of wing bud mesenchymal cells with exogenous sPLA2 promoted cell
      death by activating MMP-9 (matrix metalloproteinase-9) and increasing type I
      collagen degradation. The additive chondro-inhibitory actions were induced by co
      treatment of mp-BSA (p-aminophenyl-mannopyranoside-BSA), a known ligand of the
      mannose receptor. Chondro-inhibitory actions by sPLA2 were prevented by
      functional blocking of FcRY (chicken yolk sac IgY receptor), a mannose receptor
      family member that is the orthologue of the mammalian PLA2 (phospholipase A2)
      receptor and by inhibition of ERK (extracellular-signal-regulated kinase)
      activity. CONCLUSIONS: Taken together, our results suggest that elevated levels
      of sPLA2 secreted by wing bud mesenchymal cells promote type I collagen
      degradation by MMP-9 in a manner typical of receptor-mediated signalling and that
      these events lead to cell death.

PMID- 19764902
TI  - Silencing of the mitochondrial NADH shuttle component aspartate-glutamate carrier
      AGC1/Aralar1 in INS-1E cells and rat islets.
AB  - Transfer of reducing equivalents between cytosolic compartments and the
      mitochondrial matrix is mediated by NADH shuttles. Among these, the malate
      aspartate shuttle has been proposed to play a major role in beta-cells for the
      control of glucose-stimulated insulin secretion. AGC1 or Aralar1 (aspartate
      glutamate carrier 1) is a key component of the malate-aspartate shuttle.
      Overexpression of AGC1 increases the capacity of the malate-aspartate shuttle,
      resulting in enhanced metabolism-secretion coupling, both in INS-1E cells and rat
      islets. In the present study, knockdown of AGC1 was achieved in the same beta
      cell models, using adenovirus-mediated delivery of shRNA (small-hairpin RNA).
      Compared with control INS-1E cells, down-regulation of AGC1 blunted NADH
      formation (-57%; P<0.05), increased lactate production (+16%; P<0.001) and
      inhibited glucose oxidation (-22%; P<0.01). This correlated with a reduced
      secretory response at 15 mM glucose (-25%; P<0.05), while insulin release was
      unchanged at intermediate 7.5 mM and basal 2.5 mM glucose. In isolated rat
      islets, efficient AGC1 knockdown did not alter insulin exocytosis evoked by 16.7
      mM glucose. However, 4 mM amino-oxyacetate, commonly used to block transaminases
      of the malate-aspartate shuttle, inhibited glucose-stimulated insulin secretion
      to similar extents in INS-1E cells (-66%; P<0.01) and rat islets (-56%; P<0.01).
      These results show that down-regulation of the key component of the malate
      aspartate shuttle AGC1 reduced glucose-induced oxidative metabolism and insulin
      secretion in INS-1E cells, whereas similar AGC1 knockdown in rat islets did not
      affect their secretory response.

PMID- 19764903
TI  - Sex differences in cerebral injury after severe haemorrhage and ventricular
      fibrillation in pigs.
AB  - BACKGROUND: Experimental studies of haemorrhagic shock have documented a superior
      haemodynamic response and a better outcome in female animals as compared with
      male controls. Such sexual dimorphism has, nevertheless, not been reported after
      circulatory arrest that follows exsanguination and shock. We aimed to study
      differences in cerebral injury markers after exsanguination cardiac arrest in pre
      pubertal piglets. The hypothesis was that cerebral injury is less extensive in
      female animals, and that this difference is independent of sexual hormones or
      choice of resuscitative fluid. METHODS: Thirty-two sexually immature piglets (14
      males and 18 females) were subjected to 5 min of haemorrhagic shock followed by 2
      min of ventricular fibrillation and 8 min of cardiopulmonary resuscitation, using
      three resuscitation fluid regimens (whole blood, hypertonic saline and dextran,
      or acetated Ringers' solution plus whole blood and methylene blue). Haemodynamic
      values, cellular markers of brain injury and brain histology were studied.
      RESULTS: After successful resuscitation, female piglets had significantly greater
      cerebral cortical blood flow, tended to have lower S-100beta values and a lower
      cerebral oxygen extraction ratio. Besides, in female animals, systemic and
      cerebral venous acidosis were mitigated. Female piglets exhibited a significantly
      smaller increase in neuronal nitric oxide synthase (nNOS) and inducible nitric
      oxide synthase (iNOS) expression in their cerebral cortex, smaller blood-brain
      barrier (BBB) disruption and significantly smaller neuronal injury. CONCLUSION:
      After resuscitation from haemorrhagic circulatory arrest, cerebral reperfusion is
      greater, and BBB permeability and neuronal injury is smaller in female piglets.
      An increased cerebral cortical iNOS and nNOS expression in males implies a
      mechanistic relationship with post-resuscitation neuronal injury and warrants
      further investigation.

PMID- 19764904
TI  - Effects of surfactant replacement on alveolar overdistension and plasma cytokines
      in ventilator-induced lung injury.
AB  - BACKGROUND: Overdistension of the lung causes ventilator-induced lung injury
      (VILI) accompanied by surfactant abnormalities and inflammatory changes. We
      investigated the effects of surfactant replacement on overdistension of the
      terminal airspaces and plasma cytokine levels in VILI. METHODS: VILI was induced
      by high-pressure ventilation (HPV) in rats anesthetized with pentobarbital,
      followed by ventilation for 2 h in the maintenance mode (tidal volume=10 ml/kg,
      positive end-expiratory pressure = 7.5 cmH(2)O) with or without surfactant
      replacement. The sizes of the terminal airspaces were determined after fixing the
      lungs at an airway pressure of 10 cmH(2)O on deflation. Cytokine levels were
      assessed by enzyme-linked immunosorbent assay. RESULTS: The mean ratio of the
      largest terminal airspace size class (> or = 64,000 microm(2)) was increased from
      13.4% to 32.0% by HPV (P<0.05). After maintenance-mode ventilation, the ratio
      decreased to 16.1% with surfactant replacement (P<0.05), but increased to 44.6%
      without surfactant replacement (P<0.05). Mean macrophage inflammatory protein-2
      (MIP-2) levels in the plasma increased from <0.02 to 6.9 ng/ml with HPV (P<0.05),
      and further increased to > or = 11.8 ng/ml, regardless of surfactant replacement
      after maintenance-mode ventilation. Similar tendencies were observed in the
      interleukin (IL)-6 and IL-10 levels. Tumor necrosis factor-alpha levels were
      almost negligible during the experiment. CONCLUSION: In rats with VILI,
      surfactant replacement reversed overdistension of the terminal airspaces that may
      induce barotrauma, but not upregulation of MIP-2, IL-6, and IL-10 within 2 h.

PMID- 19764905
TI  - Pre-operative fasting: a nationwide survey of German anaesthesia departments.
AB  - BACKGROUND: Shorter pre-operative fasting improves clinical outcome without an
      increased risk. Since October 2004, German Anaesthesiology Societies have
      officially recommended a fast of 2 h for clear fluids and 6 h for solid food
      before elective surgery. We conducted a nationwide survey to evaluate the current
      clinical practice in Germany. METHODS: Between July 2006 and January 2007,
      standardized questionnaires were mailed to 3751 Anaesthesiology Society members
      in leading positions requesting anonymous response. RESULTS: The overall response
      rate was 66% (n=2418). Of those, 2148 (92%) claimed familiarity with the new
      guidelines. About a third (n=806, 34%) reported full adherence to the new
      recommendations, whereas 1043 (45%) reported an eased fasting practice.
      Traditional Nil per os after midnight was still recommended by 157 (7%).
      Commonest reasons reported for adopting the new guidelines were: 'improved pre
      operative comfort' (84%), and 'increased patient satisfaction' (83%); reasons
      against were: 'low flexibility in operation room management' (19%), and
      'increased risk of aspiration' (13%). CONCLUSION: Despite the apparent
      understanding of the benefits from reduced pre-operative fasting, full
      implementation of the guidelines remains poor in German anaesthesiology
      departments.

PMID- 19764906
TI  - Dopamine increases renal oxygenation: a clinical study in post-cardiac surgery
      patients.
AB  - BACKGROUND: Imbalance of the renal medullary oxygen supply/demand relationship
      can cause ischaemic acute renal failure (ARF). The use of dopamine for
      prevention/treatment of ischaemic ARF has been questioned. It has been suggested
      that dopamine may increase renal oxygen consumption (RVO(2)) due to increased
      solute delivery to tubular cells, which may jeopardize renal oxygenation.
      Information on the effects of dopamine on renal perfusion, filtration and
      oxygenation in man is, however, lacking. We evaluated the effects of dopamine on
      renal blood flow (RBF), glomerular filtration rate (GFR), RVO(2) and renal O(2)
      demand/supply relationship, i.e. renal oxygen extraction (RO(2)Ex). METHODS:
      Twelve uncomplicated, mechanically ventilated and sedated post-cardiac surgery
      patients with pre-operatively normal renal function were studied. Dopamine was
      sequentially infused at 2 and 4 ug/kg/min. Systemic haemodynamics were evaluated
      by a pulmonary artery catheter. Absolute RBF was measured using two independent
      techniques: by the renal vein thermodilution technique and by infusion clearance
      of paraaminohippuric acid (PAH), with a correction for renal extraction of PAH.
      The filtration fraction (FF) was measured by the renal extraction of (51)Cr-EDTA.
      RESULTS: Neither GFR, tubular sodium reabsorption nor RVO(2) was affected by
      dopamine, which increased RBF (45-55%) with both methods, decreased renal
      vascular resistance (30-35%), FF (21-26%) and RO(2)Ex (28-34%). The RBF/CI ratio
      increased with dopamine. Dopamine decreased renal PAH extraction, suggestive of a
      flow distribution to the medulla. CONCLUSIONS: In post-cardiac surgery patients,
      dopamine increases the renal oxygenation by a pronounced renal pre-and post
      glomerular vasodilation with no increases in GFR, tubular sodium reabsorption or
      renal oxygen consumption.

PMID- 19764907
TI  - Evaluation of the Video Intubation Unit in morbid obese patients.
AB  - BACKGROUND: Tracheal intubation may be more difficult in morbidly obese (MO)
      patients than in the non-obese. The aim of this study was to evaluate clinically
      if the use of the Video Intubation Unit (VIU), a video-optical intubation stylet,
      could improve the laryngoscopic view compared with the standard Macintosh
      laryngoscope in this specific population. METHODS: We studied 40 MO patients
      (body mass index >35 kg/m(2)) scheduled for bariatric surgery. Each patient had a
      conventional laryngoscopy and a VIU inspection. The laryngoscopic grades (LG)
      using the Cormack and Lehane scoring system were noted and compared. Thereafter,
      the patients were randomised to be intubated with one of the two techniques. In
      one group, the patients were intubated with the help of the VIU and in the
      control group, tracheal intubation was performed conventionally. The duration of
      intubation, as well as the minimal SpO(2) achieved during the procedure, were
      measured. RESULTS: Patient characteristics were similar in both groups. Seventeen
      patients had a direct LG of 2 or 3 (no patient had a grade of 4). Out of these 17
      patients, the LG systematically improved with the VIU and always attained grade 1
      (P<0.0001). The intubation time was shorter within the VIU group, but did not
      attain significance. There was no difference in the SpO(2) post-intubation.
      CONCLUSION: In MO patients, the use of the VIU significantly improves the
      visualisation of the larynx, thereby improving the intubation conditions.

PMID- 19764908
TI  - Should dynamic parameters for prediction of fluid responsiveness be indexed to
      the tidal volume?
AB  - BACKGROUND: The respiratory variation in the pre-ejection period (Delta PEP) has
      been used to predict fluid responsiveness in mechanically ventilated patients.
      Recently, we modified this parameter (PEPV) and showed that it was a reliable
      predictor for post-cardiac surgery, mainly paced, patients when moderately low
      tidal volumes were used. One of the modifications involved tidal volume
      indexation, which had not been proposed before for dynamic parameters. The aim of
      the present animal study was to investigate whether indexation to tidal volume
      should be part of a new definition of dynamic parameters such as the case for our
      newly proposed PEPV. METHODS: Eight prone, anesthetized piglets (23-27 kg) were
      subjected to a sequence of 25% hypovolemia, normovolemia, and 25% and 50%
      hypervolemia. At each volemic level, tidal volumes were varied in three steps: 6,
      9, and 12 ml/kg. PEP variations (ms) and pulse-pressure variation (PPV) were
      measured during the three tidal volume steps at each volemic level. RESULTS: PEP
      variations increased significantly with increasing tidal volume at all volemic
      levels but 50% hypervolemia and were proportionally related to the tidal volume
      at normovolemia. PPV increased significantly with increasing tidal volume at all
      volemic levels and was roughly proportional to the tidal volume at all volemic
      levels but hypovolemia. CONCLUSION: Our study indicates that dynamic parameters
      are improved by indexing to tidal volume.

PMID- 19764909
TI  - Depth of anaesthesia and post-operative cognitive dysfunction.
AB  - BACKGROUND: A deep level of anaesthesia measured by the bispectral index has been
      found to improve processing speed as one aspect of cognitive function after
      surgery. The purpose of the present study was to assess the possible effect of
      the level of anaesthesia on post-operative cognitive dysfunction (POCD) 1 week
      after surgery, as assessed by a neuropsychological test battery. METHODS: We
      included 70 patients >60 years of age scheduled for elective non-cardiac surgery
      with general anaesthesia. The depth of anaesthesia was monitored using the
      cerebral state monitor, which provided a cerebral state index (CSI) value.
      Cognitive function was assessed by the ISPOCD neuropsychological test battery
      before and at 1 week (or hospital discharge) after surgery and POCD was defined
      as a Z score above 1.96. RESULTS: Five patients were not assessed after surgery.
      The mean CSI was 40 and 43 in patients with (N=9) and without POCD (N=56),
      respectively (P=0.41). The cumulated time of both deep anaesthesia (CSI<40) and
      light anaesthesia (CSI>60) did not differ significantly, and no significant
      correlation was found between the mean CSI and the Z score. CONCLUSION: We were
      unable to detect a significant association between the depth of anaesthesia and
      the presence of POCD 1 week after the surgery.

PMID- 19764910
TI  - Regional anaesthesia for a Caesarean section in women with cardiac disease: a
      prospective study.
AB  - BACKGROUND: We conducted a prospective observational survey of pregnant women
      with cardiac disease. The aim was to analyse and present the mode of delivery,
      outcome, and haemodynamic changes during a caesarean section under regional
      anaesthesia in women with cardiac disease. METHODS: All pregnant women with a
      cardiovascular diagnosis, except hypertension, were included in the registry.
      Based on the cardiac diagnoses, and on the New York Heart Association
      classification, a multidisciplinary group made recommendations for each patient
      and decided on the mode of delivery. The data from continuous, invasive
      haemodynamic monitoring in intermediate- and high-risk patients under regional
      anaesthesia for a caesarean section were analysed and presented. RESULTS: The
      hospital had approximately 9000 deliveries in the period from November 2003 to
      April 2008. A total of 113 pregnancies in 107 women were included. Thirty-two
      (28.3%) pregnancies were classified into the high-risk category. Of 103
      deliveries, caesarean sections were performed in 59 (52.2%) cases, with regional
      anaesthesia in 51 patients (18 emergencies), general anaesthesia in eight
      patients (five emergencies), and a planned vaginal delivery in 44 patients. There
      was no mortality among the mothers or the babies during the hospital stay or 6
      months postpartum. Pre-operative cardiovascular stability during the caesarean
      section was maintained by volume and phenylephrine infusion guided by invasive
      monitoring of haemodynamic variables. CONCLUSION: Our study suggests that
      pregnant women with cardiac disease may safely deliver the baby by a caesarean
      section under regional anaesthesia. According to our findings, haemodynamic
      stability can be obtained by titrated regional anaesthesia, intravenous (i.v.)
      volume, phenylephrine infusion, and small repeated doses of i.v. oxytocin guided
      by invasive monitoring.

PMID- 19764911
TI  - Propofol has anti-inflammatory effects on alveolar type II epithelial cells.
AB  - BACKGROUND: We investigated whether lipopolysaccharide (LPS) induced inflammation
      in alveolar epithelial type II (ATII) cells is through cluster of differentiation
      14 (CD14) and Toll-like receptor 4 (TLR4) and the effect of different dosages of
      propofol on the inflammation in primary cultured rat ATII cells. METHODS:
      Cultured ATII cells were randomly assigned to one of the following five groups:
      Group C: untreated group (control) cultured in the absence of propofol and LPS;
      Group LPS: treated with 1 microg/ml LPS; Group P1: treated with 1 microg/ml LPS
      and 25 microM propofol; Group P2: treated with 1 microg/ml LPS and 50 microM
      propofol; Group P3: treated with 1 microg/ml LPS and 100 microM propofol. ATII
      cells in all groups were cultured at 37 degrees C for 3 h. CD14 and TLR4 mRNA was
      detected using real-time polymerase chain reaction. Western blot was used to
      detect CD14 and TLR4 protein expression. CD14 and TLR4 expression on the ATII
      cells was imaged using immunofluorescence. Tumor necrosis factor-alpha (TNF
      alpha) production was determined using an ELISA kit. RESULTS: LPS stimulation
      resulted in an increased CD14 and TLR4 expression and increased TNF-alpha
      production in ATII cells. Propofol, at concentrations > or = 50 microM,
      significantly (P<0.05) and dose-dependently decreased CD14 and TLR4 mRNA
      expression and protein expression in ATII cells. This was accompanied by a
      decrease in TNF-alpha production (P<0.05). CONCLUSION: These results suggest that
      propofol, at clinically relevant concentrations, can reduce inflammatory
      responses in LPS-induced ATII cells injury through downregulation of CD14 and
      TLR4 expression.

PMID- 19764912
TI  - Therapeutic interference with EphrinB2 signalling inhibits oxygen-induced
      angioproliferative retinopathy.
AB  - PURPOSE: To investigate whether EphrinB2 (EfnB2) or EphB4 influence retinal
      angiogenesis under physiological or pathological conditions. METHODS: Using the
      mouse model of oxygen-induced proliferative retinopathy (OIR), the expression of
      EfnB2, EphB4, vascular endothelial growth factor (VEGF), VEGFR1 and VEGFR2 was
      quantified by quantitative polymerase chain reaction (qPCR) and localized in
      EfnB2- and EphB4-lacZ mice. Angioproliferative retinopathy was manipulated by
      intravitreal injection of dimeric EfnB2 and monomeric or dimeric EphB4. RESULTS:
      Dimeric EphB4 (EphB4-Fc) and EfnB2 (EfnB2-Fc) enhanced hypoxia-induced
      angioproliferative retinopathy but not physiological angiogenesis. Monomeric
      EphB4 (sEphB4) reduced angiogenesis. The messenger RNA (mRNA) level of EfnB2
      increased significantly in the hyperoxic phase (P7-P12), while EphB4, VEGF,
      VEGFR1 and VEGFR2 showed a significant - up to fivefold - increased expression at
      P14, the start of morphologically visible vasoproliferation caused by relative
      hypoxia. CONCLUSION: The ephrin/Eph system is involved in angioproliferative
      retinopathy. Stimulation of EphB4 and EfnB2 signalling using EfnB2-Fc and EphB4
      Fc, respectively, enhanced hypoxia-induced angiogenesis. In contrast, sEphB4
      inhibited hypoxia-induced angiogenesis. Therefore, angiogenesis is enhanced by
      signalling through both EphB4 (forward) and EfnB2 (reverse). The distinction in
      the expression kinetics of EphB4 and EfnB2 indicates that they govern two
      different signalling pathways and are regulated in diverse ways. sEphB4 might be
      a useful drug for antiangiogenic therapy.

PMID- 19764913
TI  - Macular hole formation after vitrectomy for retinal detachment.

PMID- 19764914
TI  - Automatic and manual segmentation of healthy retinas using high-definition
      optical coherence tomography.
AB  - PURPOSE: This study compared automatic- and manual segmentation modalities in the
      retina of healthy eyes using high-definition optical coherence tomography (HD
      OCT). METHODS: Twenty retinas in 20 healthy individuals were examined using an HD
      OCT system (Carl Zeiss Meditec, Inc.). Three-dimensional imaging was performed
      with an axial resolution of 6 MUm at a maximum scanning speed of 25,000 A
      scans/second. Volumes of 6 * 6 * 2 mm were scanned. Scans were analysed using a
      matlab-based algorithm and a manual segmentation software system (3D-Doctor). The
      volume values calculated by the two methods were compared. RESULTS: Statistical
      analysis revealed a high correlation between automatic and manual modes of
      segmentation. The automatic mode of measuring retinal volume and the
      corresponding three-dimensional images provided similar results to the manual
      segmentation procedure. Both methods were able to visualize retinal and
      subretinal features accurately. CONCLUSIONS: This study compared two methods of
      assessing retinal volume using HD-OCT scans in healthy retinas. Both methods were
      able to provide realistic volumetric data when applied to raster scan sets.
      Manual segmentation methods represent an adequate tool with which to control
      automated processes and to identify clinically relevant structures, whereas
      automatic procedures will be needed to obtain data in larger patient populations.

PMID- 19764915
TI  - Cataract surgery in a population-based cohort of patients with type 1 diabetes:
      long-term incidence and risk factors.
AB  - PURPOSE: To estimate the long-term cumulative incidence of cataract surgery and
      associated risk factors in a 25-year follow-up of a population-based cohort of
      patients with type 1 diabetes. METHODS: Based on insulin prescriptions, a
      population-based cohort of 727 patients with type 1 diabetes was identified in
      1973. In 1981-1982 diabetic retinopathy was graded and other markers of diabetes
      were measured in 573 patients who participated in a clinical baseline
      examination. Based on data from the Danish National Patient Registry, patients
      were followed until November 2006 and cataract surgery was evaluated during
      follow-up. RESULTS: The 25-year crude cumulative incidence of cataract surgery
      was 20.8% (117 of 562 patients at risk), corresponding to a mortality-adjusted
      incidence of 29.4% [95% confidence interval (CI) 25.6-33.1%]. Median age and
      duration of diabetes at the time of surgery were 59.3 and 42 years, respectively.
      Cataract surgery in the cohort took place approximately 20 years earlier compared
      to non-diabetic persons. In a multivariate regression analysis, baseline age
      [hazard ratio (HR) 1.89 per 10 years, 95% CI 1.46-2.27] and maculopathy (HR 1.89,
      95% CI 1.05-3.40) were the only statistically significant predictors of cataract
      surgery. Duration of diabetes, gender, glycaemic regulation, proteinuria,
      smoking, blood pressure and level of retinopathy were not associated with
      cataract surgery. CONCLUSION: Type 1 diabetes is associated with a high long-term
      incidence of cataract surgery. The association between maculopathy and subsequent
      cataract surgery is a novel finding and should be addressed in future studies.

PMID- 19764916
TI  - Correlation of matrix metalloproteinase levels with the grade of proliferative
      vitreoretinopathy in the subretinal fluid and vitreous during rhegmatogenous
      retinal detachment.
AB  - PURPOSE: We investigated the activity of matrix metalloproteinase (MMP)-2 and -9
      and their latent pro-forms (proMMP-2, -9), and protein levels of MMP-1, -3, -8
      and tissue inhibitor of MMPs (TIMP)-1 in the subretinal fluid (SRF) and vitreous
      of patients with rhegmatogenous retinal detachment (RRD). Potential correlations
      with proliferative vitreoretinopathy (PVR) grade were determined. METHODS: Thirty
      seven SRF and 32 vitreous samples from RRD patients and nine vitreous samples
      from human organ donors (controls), were collected and assayed for MMP-1, -3, 
      8/TIMP-1 levels using enzyme-linked immunosorbent assay (ELISA), and for proMMP
      2, -9, MMP-2, -9 activity employing gelatine zymography. RESULTS: ProMMP-2, -9,
      MMP-1, -3, -9, TIMP-1 were significantly higher in the SRF and vitreous of RRD
      patients compared to the vitreous of organ donors. MMP-8 levels were higher in
      RRD patients' SRF. Regarding PVR grade, MMPs and TIMP-1 were differentially
      present in SRF and vitreous. PVR grade correlated significantly with the levels
      of MMP-2 in SRF, while proMMP-2, MMP-1, -2, -3, -8, -9 and TIMP-1 levels
      correlated with PVR grade in the vitreous. CONCLUSION: MMP/TIMP-1 levels are
      elevated in SRF and vitreous during RRD. Significant correlations between PVR
      grade and MMP-2 in SRF and proMMP-2, MMP-1, -2, -3, -8, -9 and TIMP-1 levels in
      vitreous were revealed. Investigation of MMP activity in vitreous may provide
      more valid conclusions compared to SRF pertaining to the role of the MMPs during
      RRD. The observations of the present study suggest a possible role for MMPs and
      TIMP-1 in PVR pathophysiology.

PMID- 19764917
TI  - Circulating bone-marrow-derived endothelial precursor cells contribute to
      neovascularization in diabetic epiretinal membranes.
AB  - PURPOSE: The role of vasculogenesis, recruitment and differentiation of
      circulating bone-marrow-derived endothelial precursor cells into mature
      endothelium in proliferative diabetic retinopathy (PDR) remains undefined. We
      investigated the presence of bone-marrow-derived endothelial precursor cells and
      the expression of the chemotactic pathway SDF-1 /CXCL12)CXCR4 in PDR epiretinal
      membranes. METHODS: Membranes from eight patients with active PDR and nine
      patients with inactive PDR were studied by immunohistochemistry using antibodies
      against CD133, vascular endothelial growth factor receptor-2 (VEGFR-2), CD14, SDF
      1 and CXCR4. RESULTS: Blood vessels expressed CD133, VEGFR-2, CD14, SDF-1 and
      CXCR4 in 10, 10, 10, seven and seven out of 17 membranes, respectively. There
      were significant correlations between number of blood vessels expressing CD34 and
      number of blood vessels expressing CD133 (r(s) = 0.646; p = 0.005), VEGFR-2 (r(s)
      = 0.704; p = 0.002), CD14 (r(s) = 0.564; p = 0.018) and SDF-1 (r(s) = 0.577; p =
      0.015). Stromal cells in close association with blood vessels expressed CD133,
      VEGFR-2, CD14 and CXCR4 in 10, 12, 13 and 14 membranes, respectively. The number
      of blood vessels expressing CD133 (p = 0.013), VEGFR-2 (p = 0.005), CD14 (p =
      0.008) and SDF-1 (p = 0.005), and stromal cells expressing CD133 (p = 0.003),
      VEGFR-2 (p = 0.013) and CD14 (p = 0.002) was significantly higher in active
      membranes than in inactive membranes. CONCLUSION: Bone-marrow-derived CD133(+)
      endothelial progenitor cells and CD14(+) monocytes may contribute to
      vasculogenesis in PDR.

PMID- 19764918
TI  - Rieger syndrome is not associated with PAX6 deletion: a correction to Acta
      Ophthalmol Scand 2001: 79: 201-203.

PMID- 19764919
TI  - Factors associated with non-penetrating deep sclerectomy failure in controlling
      intraocular pressure.
AB  - PURPOSE: To identify factors related to non-penetrating deep sclerectomy (NPDS)
      failure in controlling intraocular pressure (IOP). METHODS: A case-control study
      was performed through a logistic regression modelling. All cases and controls had
      at least 2 years of follow-up. Cases comprised eyes that had undergone an NPDS
      and presented an end-point IOP > 18 mmHg; controls consisted of eyes that had
      undergone an NPDS and achieved an end-point IOP < 18 mmHg without medication.
      Cases and controls were paired by sex and postoperative time. The following
      independent variables were tested: race, previous ocular surgery, number of
      topical medications prior to surgery, age, preoperative IOP, severity of
      glaucomatous visual field loss, use of mitomycin C (MMC), YAG laser goniopuncture
      and IOP in the first day after surgery. RESULTS: Two hundred and sixty-nine eyes
      were studied (136 cases and 133 controls). Absence of intraoperative MMC and high
      preoperative IOP were related to an end-point IOP > 18 mmHg after 2 years of
      follow-up. CONCLUSION: Two factors seem to be associated to NPDS failure: the
      absence of intraoperative MMC and preoperative IOP.

PMID- 19764920
TI  - The transient value of classifying preschool wheeze into episodic viral wheeze
      and multiple trigger wheeze.
AB  - BACKGROUND: A recently proposed method for classifying preschool wheeze is to
      describe it as either episodic (viral) wheeze or multiple trigger wheeze. In
      research studies, phenotype is generally determined by retrospective
      questionnaire. AIM: To determine whether recently proposed phenotypes of
      preschool wheeze are stable over time. METHODS: In all, 132 two to six-year-old
      children with doctor diagnosed asthma on maintenance inhaled corticosteroids were
      classified as having episodic (viral) wheeze or multiple trigger wheeze at a
      screening visit and then followed up at three-monthly intervals for a year. At
      each follow-up visit, standardized questionnaires were used to determine whether
      the subjects wheezed only with, or also in the absence of colds. Stability of the
      phenotypes was assessed at the end of the study. RESULTS: Phenotype as determined
      by retrospective parental report at the start of the study was not predictive of
      phenotype during the study year. Phenotypic classification remained the same in
      45.9% of children and altered in 54.1% of children. CONCLUSION: When children
      with preschool wheeze are classified into episodic (viral) wheeze or multiple
      trigger wheeze based on retrospective questionnaire, the classification is likely
      to change significantly within a 1-year period.

PMID- 19764921
TI  - Request for clarifications on paper published.

PMID- 19764922
TI  - Routine developmental screening at 5.5 and 7 years of age is not an efficient
      predictor of attention-deficit / hyperactivity disorder at age 10.
AB  - AIM: The aim of this study was to assess the efficiency of developmental
      screening for deficits in attention, motor control and perception or attention
      deficit/hyperactivity disorder (DAMP/ADHD) at 5.5 and 7 years of age for
      diagnosing ADHD in grade 4. METHOD: The study population consisted of 442
      children from a cohort study of ADHD in 10-year olds in one municipality in
      Stockholm County. Sensitivity, specificity and positive predictive value of a
      developmental screening at 5.5 and at 7 years of age for being diagnosed with
      ADHD at 10 years of age was calculated. RESULTS: The sensitivity was 44%, the
      specificity 85% and the positive predictive value for having a diagnosis of
      pervasive ADHD in 4th grade was 15%, when at least two deviations in nine items
      was used as the cut-off point in 5.5-year screening at Child Health Centres
      (CHCs). With a cut-off score of at least two deviations in four items rated by
      parents or and teachers in 1st grade, these estimates were 58%, 81% and 15%
      respectively. CONCLUSION: This study demonstrates that developmental screening
      for DAMP/ADHD at 5.5 and 7 years of age does not identify children who are
      diagnosed with ADHD in grade 4 with a high degree of selectivity.

PMID- 19764923
TI  - Impact of skin tone on the performance of a transcutaneous jaundice meter.
AB  - AIM: To evaluate the performance of the Konica Minolta/Air-Shields JM-103
      jaundice meter on the basis of infant skin tone during the early neonatal period.
      METHODS: Infants were prospectively categorized into light, medium and dark skin
      tone groups relative to two reference colours. Transcutaneous bilirubin readings
      were taken at predetermined intervals through the early neonatal period on a
      convenience sample of 938 healthy infants > or =37 weeks gestation. Serum
      bilirubin measurements were drawn routinely with metabolic studies and repeated
      in the presence of an elevated transcutaneous reading or clinically significant
      jaundice. RESULTS: Multivariate linear regression analysis showed a significant
      impact on serum and transcutaneous bilirubin agreement by skin tone. Highest
      precision and lowest bias were observed for medium skin toned infants. Greater
      disagreement between serum and transcutaneous measurements was noted at serum
      bilirubin concentrations >200 micromol/L. Insufficient numbers of dark skin toned
      infants were enrolled to evaluate fully the performance of the jaundice meter for
      this group. CONCLUSION: The JM-103 jaundice meter displayed good correlation with
      serum bilirubin concentrations in light and medium skin tone infants, although it
      showed a tendency to under-read in the lighter skin tone group and to over-read
      in the darker skin tone group. The device shows excellent performance
      characteristics for use as a screening device.

PMID- 19764924
TI  - Prenatal and postnatal parental smoking and acute otitis media in early
      childhood.
AB  - AIM: To explore the associations between acute otitis media in early childhood
      and prenatal and postnatal tobacco smoke exposure. METHODS: Subjects were 32 077
      children born between 2000 and 2005 in the Norwegian Mother and Child Study with
      questionnaire data on tobacco smoke exposure and acute otitis media up to 18
      months of age. Multivariate regression models were used to obtain adjusted
      relative risks for acute otitis media. RESULTS: Acute otitis media was slightly
      more common in children exposed to parental smoking. The incidence from 0 to 6
      months was 4.7% in unexposed children and 6.0% in children exposed both
      prenatally and postnatally. After adjusting for postnatal exposure and
      covariates, the relative risk for acute otitis media 0-6 months when exposed to
      maternal smoking in pregnancy was 1.34, 95% confidence interval: 1.06-1.69.
      Maternal smoking in pregnancy was associated with acute otitis media up to 12
      months of age. Compared with non-exposed children, there was a slightly increased
      risk of recurrent acute otitis media for children exposed both prenatally and
      postnatally with a relative risk of 1.24, 95% confidence interval: 1.01-1.52.
      CONCLUSION: Even in a cohort with relatively low exposure levels of parental
      smoking, maternal smoking in pregnancy was associated with an increased risk of
      acute otitis media in early childhood.

PMID- 19764925
TI  - Abstracts of the 50th Annual Meeting of the European Society for Paediatric
      Research. October 9-12, 2009. Hamburg, Germany.

PMID- 19764927
TI  - The 5/95 gap in the indexation of psychiatric journals of low- and middle-income
      countries.
AB  - OBJECTIVE: To investigate the relationship between science production and the
      indexation level of low- and middle-income countries (LAMIC) journals in
      international databases. METHOD: Indicators of productivity in research were
      based on the number of articles produced over the 1994-2004 period. A survey in
      both Medline and ISI/Thomson was conducted to identify journals according to
      their country of origin. A WPA Task Force designed a collaborative process to
      assess distribution and quality of non-indexed LAMIC journals. RESULTS: Twenty
      LAMIC were found to present more than 100 publications and a total of 222 indexed
      psychiatric journals were found, but only nine were from LAMIC. The Task Force
      received 26 questionnaires from editors of non-indexed journals, and concluded
      that five journals would meet criteria for indexation. CONCLUSION: Barriers to
      indexation of journals contribute to the difficulties in achieving fair
      representation in the main literature databases for the scientific production in
      these countries.

PMID- 19764926
TI  - The relationship between childhood trauma history and the psychotic subtype of
      major depression.
AB  - OBJECTIVE: Increasing evidence exists linking childhood trauma and primary
      psychotic disorders, but there is little research on patients with primary
      affective disorders with psychotic features. METHOD: The sample consisted of
      adult out-patients diagnosed with major depressive disorder (MDD) at clinic
      intake using a structured clinical interview. Patients with MDD with (n = 32) vs.
      without psychotic features (n = 591) were compared as to their rates of different
      types of childhood trauma. RESULTS: Psychotic MDD patients were significantly
      more likely to report histories of physical (OR = 2.81) or sexual abuse (OR =
      2.75) compared with non-psychotic MDD patients. These relationships remained
      after controlling for baseline differences. Within the subsample with comorbid
      post-traumatic stress disorder, patients with psychotic MDD were significantly
      more likely to report childhood physical abuse (OR = 3.20). CONCLUSION: Results
      support and extend previous research by demonstrating that the relationship
      between childhood trauma and psychosis is found across diagnostic groups.

PMID- 19764928
TI  - Altered interaction between cardiac vagal influence and delta sleep EEG suggests
      an altered neuroplasticity in patients suffering from major depressive disorder.
AB  - OBJECTIVE: Major depressive disorder (MDD), which is associated with altered
      neuroplasticity and increased relative cardiac sympathic activity, enhances the
      risk of cardiovascular pathologies. Interaction between cardiac sympatho-vagal
      indexes and delta sleep power is probably altered in MDD. METHOD: Sleep
      characteristics and cardiac sympatho-vagal indexes of 10 depressive patients were
      compared to 10 control men across the first three non-rapid eye movement (NREM)
      REM cycles. Interaction between normalized high frequency (HF) and delta power
      bands was studied using coherence analysis. RESULTS: Patients showed increased
      sleep latency, stage 1 and wake durations. No differences in heart rate
      variabilities were observed: Total power, HF and RR-interval decreased from NREM
      to REM sleep and wakefulness in both groups. Gain value was lower in patients
      while coherence and phase shift were similar between groups. Modifications in HF
      appear 8 min before modifications in delta. CONCLUSION: Major depressive disorder
      is related to an altered link between cardiac vagal influence and delta sleep,
      suggesting disorders in cardiovascular controls and an altered neuroplasticity.

PMID- 19764929
TI  - Caenorhabditis elegans PI3K mutants reveal novel genes underlying exceptional
      stress resistance and lifespan.
AB  - Two age-1 nonsense mutants, truncating the class-I phosphatidylinositol 3-kinase
      catalytic subunit (PI3K(CS)) before its kinase domain, confer extraordinary
      longevity and stress-resistance to Caenorhabditis elegans. These traits, unique
      to second-generation homozygotes, are blunted at the first generation and are
      largely reversed by additional mutations to DAF-16/FOXO, a transcription factor
      downstream of AGE-1 in insulin-like signaling. The strong age-1 alleles (mg44,
      m333) were compared with the weaker hx546 allele on expression microarrays,
      testing four independent cohorts of each allele. Among 276 genes with
      significantly differential expression, 92% showed fewer transcripts in adults
      carrying strong age-1 alleles rather than hx546. This proportion is significantly
      greater than the slight bias observed when contrasting age-1 alleles to wild-type
      worms. Thus, transcriptional changes peculiar to nonsense alleles primarily
      involve either gene silencing or failure of transcriptional activation. A subset
      of genes responding preferentially to age-1-nonsense alleles was reassessed by
      real-time polymerase chain reaction, in worms bearing strong or weak age-1
      alleles; nearly all of these were significantly more responsive to the age
      1(mg44) allele than to age-1(hx546). Additional mutation of daf-16 reverted the
      majority of altered mg44-F2 expression levels to approximately wild-type values,
      although a substantial number of genes remained significantly distinct from wild
      type, implying that age-1(mg44) modulates transcription through both DAF-16/FOXO
      dependent and -independent channels. When age-1-inhibited genes were targeted by
      RNA interference (RNAi) in wild-type or age-1(hx546) adults, most conferred
      significant oxidative-stress protection. RNAi constructs targeting two of those
      genes were shown previously to extend life, and RNAi's targeting five novel genes
      were found here to increase lifespan. PI3K-null mutants may thus implicate novel
      mechanisms of life extension.

PMID- 19764930
TI  - Ethanol is self-administered into the nucleus accumbens shell, but not the core:
      evidence of genetic sensitivity.
AB  - BACKGROUND: A previous study indicated that selectively bred alcohol-preferring
      (P) rats self-administered ethanol (EtOH) directly into the posterior ventral
      tegmental area at lower concentrations than Wistar rats. The present study was
      undertaken to determine involvement of the nucleus accumbens (Acb) with EtOH
      reinforcement, and a relationship between genetic selection for high alcohol
      preference and sensitivity of the Acb to the reinforcing effects of EtOH.
      METHODS: Adult P and Wistar rats were assigned to groups that self-infused 0 to
      300 mg% EtOH into the Acb shell (AcbSh) or Acb Core (AcbC). Rats were placed into
      2-lever (active and inactive) operant chambers and given EtOH for the first 4
      sessions (acquisition), artificial cerebrospinal fluid (aCSF) for sessions 5 and
      6 (extinction), and EtOH again in session 7 (reinstatement). Responding on the
      active lever produced a 100-nl injection of the infusate. RESULTS: Alcohol
      preferring rats self-infused 75 to 300 mg% EtOH, whereas Wistar rats reliably
      self-infused 100 and 300 mg% EtOH into the AcbSh. Both P and Wistar rats reduced
      responding on the active lever when aCSF was substituted for EtOH, and reinstated
      responding in session 7 when EtOH was restored. EtOH was not self-infused into
      the AcbC by P or Wistar rats. CONCLUSIONS: The present results indicate that the
      AcbSh, but not AcbC, is a neuroanatomical structure that mediates the reinforcing
      actions of EtOH. The data also suggest that, compared to Wistar rats, the AcbSh
      of P rats is more sensitive to the reinforcing effects of EtOH.

PMID- 19764931
TI  - Acute effects of low doses of red wine on cardiac conduction and repolarization
      in young healthy subjects.
AB  - BACKGROUND: Moderate to high blood concentrations of ethanol have been shown to
      yield acute changes in cardiac electrophysiological properties, but the effect of
      low concentrations have never been assessed. The role of concomitant changes in
      clinical variables or cardiac dimensions is also still unknown. This study aimed
      at exploring the acute effects of low doses of ethanol, administered as Italian
      red wine, on conduction, depolarization, and repolarization electrocardiographic
      (ECG) intervals in a population of healthy subjects. METHODS: Forty healthy young
      volunteers drank a low quantity of red wine (5 ml/kg), and an equal volume of
      fruit juice in separate experiments. Heart rate, P-wave duration, PR interval,
      QRS duration, QT interval, corrected QT interval, QT dispersion, and corrected QT
      dispersion were assessed at baseline and after 60 minutes from challenge.
      RESULTS: Mean blood ethanol concentration after drinking was 0.48 +/- 0.06 g/l.
      Compared to the control challenge, significant changes after red wine intake were
      observed in P-wave duration (from 101 +/- 11 to 108 +/- 14 milliseconds, p =
      0.0006), PR interval (from 153 +/- 15 to 167 +/- 17 milliseconds, p < 0.0001), QT
      interval (from 346 +/- 28 to 361 +/- 24 milliseconds, p < 0.0001), and corrected
      QT interval (from 388 +/- 24 to 402 +/- 30 milliseconds, p = 0.0006). None of
      these changes showed correlations with modifications in clinical or
      echocardiographic variables. In multivariate analyses aimed at exploring
      predictors of ECG changes, none of the variables entered the final models.
      CONCLUSIONS: Low doses of red wine acutely slow cardiac conduction and prolong
      repolarization in normal individuals. These changes are poorly predictable. The
      potential arrhythmogenic impact of these effects is worthy of exploration.

PMID- 19764932
TI  - Catching the alcohol buzz: an examination of the latent factor structure of
      subjective intoxication.
AB  - BACKGROUND: The goal of this study was to examine the latent structure among
      measures of alcohol-induced subjective feelings of intoxication from a behavioral
      pharmacology perspective. METHODS: Data on subjective intoxication, measured
      concomitantly by the Subjective High Assessment Scale, Biphasic Alcohol Effect
      Scale, and the Short Version of the Profile of Mood States, were collected at 3
      levels of breath alcohol concentration during an alcohol administration study in
      a sample of heavy drinkers (n = 135). RESULTS: Results of exploratory factor
      analyses supported a 3-factor model which captured the following dimensions of
      subjective intoxication: (1) stimulation and other pleasant effects, (2) sedative
      and unpleasant effects, and (3) alleviation of tension and negative mood. The
      tension-reduction factor was most consistently associated with more frequent
      drinking and alcohol problems in this sample. CONCLUSIONS: These findings support
      the notion that the neuropharmacological and behavioral effects of alcohol are
      multifaceted and cannot be simply defined as either positive or negative. Rather,
      moderate levels of intoxication appear to have concomitant dimensions of positive
      reinforcement, negative reinforcement, and punishment. This study also suggests
      that factor scores may be useful in future alcohol administration studies to
      reduce the number of comparisons and perhaps increase statistical power to detect
      meaningful effects.

PMID- 19764933
TI  - Suicide and alcohol: do outlets play a role?
AB  - BACKGROUND: The purpose of this study was to determine whether the number of
      alcohol outlets in local and adjacent areas, in particular bars, was related over
      time to completed suicide and suicide attempts. There is evidence both from
      studies of individuals and time series aggregate studies, mostly at the national
      level, of substantial alcohol involvement in suicide, but no small-area,
      longitudinal studies have been carried out. The present study is the first that
      is both longitudinal and based on a large number of small spatial units,
      California zip codes, a level of resolution permitting analysis of the
      relationship between local alcohol access and suicide rates over time. METHOD:
      Longitudinal data were obtained from 581 consistently defined zip code areas over
      6 years (1995-2000) using data from the California Index Locations Database, a
      geographic information system that contains both population and place information
      with spatial attributes for the entire state. Measures obtained from each zip
      code included population characteristics (e.g., median age) and place
      characteristics (e.g., numbers of retail and alcohol outlets) which were related
      in separate analyses to (i) suicide mortality and (ii) the number of
      hospitalizations for injuries caused by suicide attempts. The effect of place
      characteristics in zip code areas adjacent to each of the 581 local zip codes
      (spatial lags) was also assessed. Analysis methods were random effects models
      corrected for spatial autocorrelation. RESULTS: Completed suicide rates were
      higher in zip code areas with greater local and lagged bar densities; and higher
      in areas with greater local but not lagged off-premise outlet densities. Whereas
      completed suicide rates were lower among blacks and Hispanics, completed suicide
      rates were higher among low income, older whites living in less densely populated
      areas, that is, rural areas. Rates of suicide attempts were higher in zip code
      areas with greater local but not lagged bar densities, and higher among low
      income younger whites living in smaller households and in rural areas. Rates of
      attempted suicide were also higher among blacks. Completed suicide and suicide
      attempt rates were lower in zip code areas with greater local restaurant
      densities; there were no lagged effects for restaurants. CONCLUSIONS: Bar
      densities in particular appear related to suicide, meaning, because this is an
      aggregate-level spatial analysis, that suicides, both attempted and completed,
      occur at greater rates in rural community areas with greater bar densities.
      Because the suicide rate is highest in rural areas, this study suggests that
      although the number of completed and attempted suicides is no doubt greater in
      absolute numbers in urban areas, the suicide rate, both completed and attempted,
      is greater in rural areas, which draws attention, perhaps much needed, to the
      problems of rural America.

PMID- 19764934
TI  - The interaction of reward genes with environmental factors in contribution to
      alcoholism in mexican americans.
AB  - BACKGROUND: Alcoholism is a polygenic disorder resulting from reward deficiency;
      polymorphisms in reward genes including serotonin transporter (5-HTT)-linked
      polymorphic region (5-HTTLPR), A118G in opioid receptor mu1 (OPRM1), and -141C
      Insertion/Deletion (Ins/Del) in dopamine receptor D2 (DRD2) as well as
      environmental factors (education and marital status) might affect the risk of
      alcoholism. Objective of the current study was to examine the main and
      interacting effect of these 3 polymorphisms and 2 environmental factors in
      contribution to alcoholism in Mexican Americans. METHODS: Genotyping of 5-HTTLPR,
      OPRM1 A118G, and DRD2-141C Ins/Del was performed in 365 alcoholics and 338
      nonalcoholic controls of Mexican Americans who were gender- and age-matched.
      Alcoholics were stratified according to tertiles of MAXDRINKS, which denotes the
      largest number of drinks consumed in one 24-hour period. Data analysis was done
      in the entire data set and in each alcoholic stratum. Multinomial logistic
      regression was conducted to explore the main effect of 3 polymorphisms and 2
      environmental factors (education and marital status); classification tree,
      generalized multifactor dimensionality reduction (GMDR) analysis, and
      polymorphism interaction analysis version 2.0 (PIA 2) program were used to study
      factor interaction. RESULTS: Main effect of education, OPRM1, and DRD2 was
      detected in alcoholic stratum of moderate and/or largest MAXDRINKS with education
      < or =12 years, OPRM1 118 A/A, and DRD2 -141C Ins/Ins being risk factors.
      Classification tree analysis, GMDR analysis, and PIA 2 program all supported
      education*OPRM1 interaction in alcoholics of largest MAXDRINKS with education <
      or =12 years coupled with OPRM1 A/A being a high risk factor; dendrogram showed
      synergistic interaction between these 2 factors; dosage-effect response was also
      observed for education*OPRM1 interaction. No definite effect of marital status
      and 5-HTTLPR in pathogenesis of alcoholism was observed. CONCLUSIONS: Our results
      suggest main effect of education background, OPRM1 A118G, and DRD2 -141C Ins/Del
      as well as education*OPRM1 interaction in contribution to moderate and/or severe
      alcoholism in Mexican Americans. Functional relevance of these findings still
      needs to be explored.

PMID- 19764935
TI  - Evidence for an interaction between age at first drink and genetic influences on
      DSM-IV alcohol dependence symptoms.
AB  - BACKGROUND: Research suggests that individuals who start drinking at an early age
      are more likely to subsequently develop alcohol dependence. Twin studies have
      demonstrated that the liability to age at first drink and to alcohol dependence
      are influenced by common genetic and environmental factors, however, age at first
      drink may also environmentally mediate increased risk for alcohol dependence. In
      this study, we examine whether age at first drink moderates genetic and
      environmental influences, via gene x environment interactions, on DSM-IV alcohol
      dependence symptoms. METHODS: Using data on 6,257 adult monozygotic and dizygotic
      male and female twins from Australia, we examined the extent to which age at
      first drink (i) increased mean alcohol dependence symptoms and (ii) whether the
      magnitude of additive genetic, shared, and nonshared environmental influences on
      alcohol dependence symptoms varied as a function of decreasing age. Twin models
      were fitted in Mx. RESULTS: Risk for alcohol dependence symptoms increased with
      decreasing age at first drink. Heritable influences on alcohol dependence
      symptoms were considerably larger in those who reported an age at first drink
      prior to 13 years of age. In those with later onset of alcohol use, variance in
      alcohol dependence was largely attributable to nonshared environmental variance
      (and measurement error). This evidence for unmeasured gene x measured environment
      interaction persisted even when controlling for the genetic influences that
      overlapped between age at first drink and alcohol dependence symptoms.
      CONCLUSIONS: Early age at first drink may facilitate the expression of genes
      associated with vulnerability to alcohol dependence symptoms. This is important
      to consider, not only from a public health standpoint, but also in future genomic
      studies of alcohol dependence.

PMID- 19764936
TI  - Effects of ethanol on persistent activity and up-States in excitatory and
      inhibitory neurons in prefrontal cortex.
AB  - BACKGROUND: Elucidating mechanisms that underlie the neural actions of ethanol is
      critical for understanding how this drug affects behavior. Increasing evidence
      suggests that, in addition to mid-brain dopaminergic regions, higher cortical
      structures play an important role in the pathophysiology associated with alcohol
      abuse. Previous studies from this laboratory used a novel slice co-culture system
      to demonstrate that ethanol reduces network-dependent patterns of activity in
      excitatory pyramidal neurons of the prefrontal cortex (PFC). In the present
      study, we examine the effect of ethanol on the activity of fast-spiking (FS)
      interneurons, a sub-population of neurons critically involved in shaping cortical
      activity. METHODS: Slices containing the dorsolateral PFC were prepared from
      neonatal C57 mice and maintained in culture. After 2 to 3 weeks in vitro, whole
      cell patch-clamp electrophysiology was used to monitor spontaneous episodes of
      persistent activity in prelimbic PFC neurons. In some experiments, the use
      dependent NMDA receptor blocker, MK801, was included in the pipette recording
      solution to assess the contribution of NMDA receptors to up-states. RESULTS:
      MK801 reduced up-state amplitude and revealed underlying fast EPSPs in excitatory
      pyramidal neurons while having little effect on these parameters in FS
      interneurons. Despite this difference, ethanol (44 mM), significantly reduced up
      state duration and up-state area in both pyramidal and FS interneurons.
      CONCLUSIONS: These results suggest that ethanol reduces the activity of FS
      interneurons due to disruption of network-dependent activity. This would be
      expected to further impair the ability of PFC networks to carry out their normal
      function and may contribute to the adverse effects of ethanol on PFC-dependent
      behaviors.

PMID- 19764937
TI  - Polymorphisms of the IL-1 gene complex are associated with alcohol dependence in
      Spanish Caucasians: data from an association study.
AB  - BACKGROUND: There is growing evidence for involvement of pro-inflammatory
      cytokines in alcohol dependence. The aim of this study was to investigate whether
      4 functionally relevant polymorphisms of the interleukin-1 (IL-1) and tumor
      necrosis factor-alpha genes were associated with alcohol dependence and with
      measures of clinical severity and treatment outcome. METHODS: Two hundred alcohol
      dependent (AD) patients and 420 healthy controls from the same Spanish Caucasian
      population were genotyped using standard methods. Baseline and 6-month
      assessments included alcohol intake, addiction severity, and biomarkers of
      alcohol intake. RESULTS: Alcohol-dependent patients showed an excess of IL-1alpha
      889 C/T [50.8% vs. 39.3%, chi(2) (df) = 7.30 (2), uncorrected p = 0.026,
      corrected p = 0.104] and IL-1RA (86 bp)(n) A1/A1 genotypes [64.8% vs. 50.8%,
      chi(2) (df) = 12.65 (3), corrected p = 0.020]. The A1/A1 excess was associated
      with alcohol dependence only in men [69.9% vs. 49.5%, chi(2) (df) = 15.72 (2),
      corrected p < 0.001]. Six-month clinical and hematological outcome measures did
      not vary by genotype of the 4 polymorphisms. Haplotype analysis revealed an
      excess of the IL-1alpha-889 C/IL-1beta +3953 C/IL-1RA A2 haplotype in the control
      group compared with AD patients [20.0% vs. 14.1%, chi(2) (df) = 7.25 (1), p =
      0.007; odds ratio (OR) = 0.64, 95% confidence interval (CI) = 0.46-0.89] and in
      the abstainers after 6 months of treatment compared with nonabstinent patients
      [14.7% vs. 6.2%, chi(2) (df) = 5.65 (1), p = 0.017; OR = 2.56, 95% CI = 1.15
      5.62]. CONCLUSIONS: Our findings provide further tentative evidence of the role
      of IL-1 in alcohol dependence as well as evidence that the nature of the
      associations may be direct, gender-specific, or involve haplotype effects.
      However, findings from single association studies constitute tentative knowledge
      and must be interpreted carefully and precise replication is required.

PMID- 19764938
TI  - Effects of ethanol on mouse embryonic stem cells.
AB  - BACKGROUND: Fetal alcohol syndrome (FAS) reflects a constellation of congenital
      abnormalities caused by excess maternal consumption of alcohol. It is likely that
      interference with embryonic development plays a role in the pathogenesis of the
      disorder. Ethanol-induced apoptosis has been suggested as a causal factor in the
      genesis of FAS. Mouse embryonic stem (mES) cells are pluripotent cells that
      differentiate in vitro to cell aggregates termed embryoid bodies (EBs), wherein
      differentiation capacity and gene expression profile are similar to those of the
      early embryo. METHODS: To investigate the effects of ethanol during
      differentiation, mES cells were cultured on a gelatin surface in the presence of
      leukemia inhibitory factor which maintains adherent undifferentiated cells or in
      suspension to promote formation of EBs. All cells were treated (1-6 days) with 80
      mM ethanol. The pluripotency and differentiation of mES cells were evaluated by
      western blotting of stage-specific embryonic antigen (SSEA-1), transcription
      factors Oct-3/4, Sox-2, and Nanog, using alkaline phosphatase staining. Apoptosis
      (early to late stages) was assessed by fluorescence-activated cell sorting using
      TdT-mediated biotin-dUTP nick-end labelling assay and fluorescein isothiocyanate
      Annexin V/propidium iodide staining. RESULTS: Ethanol increased apoptosis during
      in vitro differentiation of mES cells to EBs, whereas undifferentiated cells were
      not affected. Ethanol exposure also interfered with pluripotency marker patterns
      causing an upregulation of SSEA-1 under self-renewal conditions. In EBs, ethanol
      delayed the downregulation of SSEA-1 and affected the regulation of transcription
      factors during differentiation. CONCLUSION: Our findings suggest that ethanol may
      contribute to the pathogenesis of FAS by triggering apoptotic pathways during
      differentiation of embryonic stem cells and deregulating early stages of
      embryogenesis.

PMID- 19764939
TI  - Priming deficiency in male subjects at risk for alcoholism: the N4 during a
      lexical decision task.
AB  - BACKGROUND: While there is extensive literature on the relationship between the
      P3 component of event-related potentials (ERPs) and risk for alcoholism, there
      are few published studies regarding other potentially important ERP components.
      One important candidate is the N4(00) component in the context of semantic
      processing, as abnormalities in this component have been reported for adult
      alcoholics. METHOD: A semantic priming task was administered to nonalcohol
      dependent male offspring (18 to 25 years) of alcoholic fathers [high risk (HR) n
      = 23] and nonalcoholic fathers [low risk (LR) n = 28] to study whether the 2
      groups differ in terms of the N4 component. Subjects were presented with 150
      words and 150 nonwords. Among the words, 50 words (primed) were preceded by their
      antonyms (prime, n = 50), whereas the remaining 50 words were unprimed. For the
      analysis, N4 amplitude and latency as well as behavioral measures for the primed
      and unprimed words were considered. RESULTS: A significant interaction effect was
      observed between semantic condition and group, where HR subjects did not show N4
      attenuation for primed stimuli. CONCLUSION: The lack of N4 attenuation to primed
      stimuli and/or inability to differentiate between primed and unprimed stimuli,
      without latency and reaction time being affected, suggest deficits in semantic
      priming, especially in semantic expectancy and/or postlexical semantic processing
      in HR male offspring. Further, it indicates that it might be an
      electrophysiological endophenotype that reflects genetic vulnerability to develop
      alcoholism.

PMID- 19764940
TI  - Tumour necrosis factor antagonists and inflammatory bowel diseases: a national
      practice survey.
AB  - BACKGROUND: Although the use of tumour necrosis factor (TNF) antagonists is
      increasingly codified, several unresolved issues remain. AIM: To conduct a French
      national survey on TNF antagonists use in inflammatory bowel disease (IBD).
      METHODS: A postal questionnaire was sent to all French gastroenterologists among
      whom 450 prescribe TNF antagonists for IBD. Only anti-TNF prescribers were
      invited to respond. RESULTS: A total of 333 questionnaires could be analysed,
      which represented a rate of survey completeness of 74%. Scheduled maintenance
      infliximab treatment was prescribed by 92% of gastroenterologists. In Crohn's
      disease in remission after 1 year of TNF antagonists, 77.4% of physicians
      continued treatment. In luminal Crohn's disease, 97% of hospital practitioners
      introduced infliximab as first-line anti-TNF therapy vs. 78% of physicians with
      nonhospital activity (P = 0.002); only 22.5% of gastroenterologists opted for
      adalimumab as first-line therapy. In Crohn's disease in remission after 6 months
      of azathioprine in combination with infliximab, 63.8% of practitioners
      discontinued azathioprine. In case of pregnancy during anti-TNF treatment, 35.1%
      of physicians discontinued therapy at the time of conception and did not
      administer anti-TNF therapy during pregnancy. CONCLUSIONS: The attitudes of
      French gastroenterologists generally reflect the recommendations regarding the
      use of anti-TNF and concomitant immunosuppressive therapy in IBD.

PMID- 19764942
TI  - Efficacy of grass pollen sublingual immunotherapy for three consecutive seasons
      and after cessation of treatment: the ECRIT study.
AB  - BACKGROUND: Data supporting a carry-over effect with sublingual immunotherapy
      (SLIT) are scarce. This randomized, double-blind, placebo-controlled study
      evaluated the efficacy, carry-over effect and safety of grass pollen SLIT using
      co-seasonal treatment. METHODS: Patients (7.9-64.7 years) with grass pollen
      allergy received ultra-rush titration with increasing doses (30, 90, 150 and 300
      IR) of a 5-grass pollen mixture every 20 min at the start of the pollen seasons,
      followed by 300 IR daily until the end of the pollen seasons. A baseline season
      (no SLIT) was followed by three consecutive treatment seasons and one follow-up
      season. Symptoms, medication and adverse events were documented and specific
      immunoglobulin (Ig)E and IgG(4) measured. RESULTS: Data were analysed for 183 of
      the 213 randomized patients. Mean treatment duration varied between seasons (81.8
      92.7 days). Combined scores (symptoms and medication) improved progressively
      across treatment seasons (up to 44.7% improvement for SLIT compared with
      baseline) and fluctuated between -11.3% and -14.8% for placebo (P < 0.05).
      Similar changes were observed for symptom scores, with a successive decrease of
      39.7% (SLIT) and fluctuations between +13.6% and -1.51% for placebo (P < 0.05).
      Combined score (P = 0.0508) and symptom score improvements (P = 0.0144) with SLIT
      continued during follow up. Increases in specific IgG(4) observed in the first
      season were sustained for SLIT vs placebo throughout treatment (P = 0.0001).
      Titration and daily SLIT were well tolerated. No serious systemic or anaphylactic
      reactions were reported. CONCLUSIONS: Seasonal SLIT with ultra-rush titration is
      well tolerated and effective from the first treatment season onwards. These data
      indicate a carry-over effect of seasonal SLIT.

PMID- 19764943
TI  - House dust mite allergy: complete removal of the provoking allergen is a primary
      therapeutic approach.

PMID- 19764944
TI  - House dust mite control measures for asthma.

PMID- 19764945
TI  - Location, Location, Location.

PMID- 19764946
TI  - MASTering Treg function to promote tolerance.

PMID- 19764947
TI  - The pathophysiology of chronic graft failure in the cardiac transplant patient.
AB  - Following cardiac transplantation, many patients develop chronic deterioration of
      graft function, which may lead to a clinical syndrome similar to native chronic
      heart failure (CHF). This condition of chronic cardiac graft failure (CGF) may
      also share pathophysiological processes comparable with that of CHF. However, the
      unique environment following cardiac transplantation may also contribute with a
      variety of unique mechanisms, deserved of special attention. This review article
      discusses the complex pathophysiology of CGF after cardiac transplantation, an
      important yet neglected condition of transplant medicine.

PMID- 19764948
TI  - Subgroup analyses in randomized controlled trials: the need for risk
      stratification in kidney transplantation.
AB  - Although randomized controlled trials (RCT) are the gold standard for
      establishing causation in clinical research, their aggregated results can be
      misleading when applied to individual patients. A treatment may be beneficial in
      some patients, but its harms may outweigh benefits in others. While conventional
      one-variable-at-a-time subgroup analyses have well-known limitations,
      multivariable risk-based analyses can help uncover clinically significant
      heterogeneity in treatment effects that may be otherwise obscured. Trials in
      kidney transplantation have yielded the finding that a reduction in acute
      rejection does not translate into a similar benefit in prolonging graft survival
      and improving graft function. This paradox might be explained by the variation in
      risk for acute rejection among included kidney transplant recipients varying the
      likelihood of benefit or harm from intense immunosuppressive regimens. Analyses
      that stratify patients by their immunological risk may resolve these otherwise
      puzzling results. Reliable risk models should be developed to investigate
      benefits and harms in rationally designed risk-based subgroups of patients in
      existing RCT data sets. These risk strata would need to be validated in future
      prospective clinical trials examining long-term effects on patient and graft
      survival. This approach may allow better individualized treatment choices for
      kidney transplant recipients.

PMID- 19764949
TI  - Potential donor-recipient MYH9 genotype interactions in posttransplant nephrotic
      syndrome after pediatric kidney transplantation.
AB  - Recurrence of focal segmental glomerulosclerosis (FSGS) with nephrotic syndrome
      is relatively common after kidney transplantation in young recipients whose
      predialysis course consists of heavy proteinuria, hypertension and subacute loss
      of kidney function. The gene(s) mediating this effect remain unknown. We report
      an unusual circumstance where kidneys recovered from a deceased African American
      male donor with MYH9-related occult FSGS (risk variants in seven of eight MYH9 E1
      haplotype single nucleotide polymorphisms) were transplanted into an African
      American male child with risk variants in four MYH9 E1 risk variants and a
      European American female teenager with two MYH9 E1 risk variants. Fulminant
      nephrotic syndrome rapidly developed in the African American recipient, whereas
      the European American had an uneventful posttransplant course. The kidney donor
      lacked significant proteinuria at the time of organ procurement. This scenario
      suggests that donor-recipient interactions in MYH9, as well as other gene-gene
      and gene-environment interactions, may lead to recurrent nephrotic syndrome after
      renal transplantation. The impact of transplanting kidneys from donors with
      multiple MYH9 risk alleles into recipients with similar genetic background at
      high risk for recurrent kidney disease needs to be determined.

PMID- 19764951
TI  - On efficiency of constrained longitudinal data analysis versus longitudinal
      analysis of covariance.
AB  - In randomized clinical trials, measurements are often collected on each subject
      at a baseline visit and several post-randomization time points. The longitudinal
      analysis of covariance in which the postbaseline values form the response vector
      and the baseline value is treated as a covariate can be used to evaluate the
      treatment differences at the postbaseline time points. Liang and Zeger (2000,
      Sankhya: The Indian Journal of Statistics, Series B 62, 134-148) propose a
      constrained longitudinal data analysis in which the baseline value is included in
      the response vector together with the postbaseline values and a constraint of a
      common baseline mean across treatment groups is imposed on the model as a result
      of randomization. If the baseline value is subject to missingness, the
      constrained longitudinal data analysis is shown to be more efficient for
      estimating the treatment differences at postbaseline time points than the
      longitudinal analysis of covariance. The efficiency gain increases with the
      number of subjects missing baseline and the number of subjects missing all
      postbaseline values, and, for the pre-post design, decreases with the absolute
      correlation between baseline and postbaseline values.

PMID- 19764952
TI  - Modeling complex phenotypes: generalized linear models using spectrogram
      predictors of animal communication signals.
AB  - A major goal of evolutionary biology is to understand the dynamics of natural
      selection within populations. The strength and direction of selection can be
      described by regressing relative fitness measurements on organismal traits of
      ecological significance. However, many important evolutionary characteristics of
      organisms are complex, and have correspondingly complex relationships to fitness.
      Secondary sexual characteristics such as mating displays are prime examples of
      complex traits with important consequences for reproductive success. Typically,
      researchers atomize sexual traits such as mating signals into a set of
      measurements including pitch and duration, in order to include them in a
      statistical analysis. However, these researcher-defined measurements are unlikely
      to capture all of the relevant phenotypic variation, especially when the sources
      of selection are incompletely known. In order to accommodate this complexity we
      propose a Bayesian dimension-reduced spectrogram generalized linear model that
      directly incorporates representations of the entire phenotype (one-dimensional
      acoustic signal) into the model as a predictor while accounting for multiple
      sources of uncertainty. The first stage of dimension reduction is achieved by
      treating the spectrogram as an "image" and finding its corresponding empirical
      orthogonal functions. Subsequently, further dimension reduction is accomplished
      through model selection using stochastic search variable selection. Thus, the
      model we develop characterizes key aspects of the acoustic signal that influence
      sexual selection while alleviating the need to extract higher-level signal traits
      a priori. This facet of our approach is fundamental and has the potential to
      provide additional biological insight, as is illustrated in our analysis.

PMID- 19764953
TI  - Identifiability of models for multiple diagnostic testing in the absence of a
      gold standard.
AB  - We discuss the issue of identifiability of models for multiple dichotomous
      diagnostic tests in the absence of a gold standard (GS) test. Data arise as
      multinomial or product-multinomial counts depending upon the number of
      populations sampled. Models are generally posited in terms of population
      prevalences, test sensitivities and specificities, and test dependence terms. It
      is commonly believed that if the degrees of freedom in the data meet or exceed
      the number of parameters in a fitted model then the model is identifiable.
      Goodman (1974, Biometrika 61, 215-231) established that this was not the case a
      long time ago. We discuss currently available models for multiple tests and argue
      in favor of an extension of a model that was developed by Dendukuri and Joseph
      (2001, Biometrics 57, 158-167). Subsequently, we further develop Goodman's
      technique, and make geometric arguments to give further insight into the nature
      of models that lack identifiability. We present illustrations using simulated and
      real data.

PMID- 19764954
TI  - Estimating haplotype effects for survival data.
AB  - Genetic association studies often investigate the effect of haplotypes on an
      outcome of interest. Haplotypes are not observed directly, and this complicates
      the inclusion of such effects in survival models. We describe a new estimating
      equations approach for Cox's regression model to assess haplotype effects for
      survival data. These estimating equations are simple to implement and avoid the
      use of the EM algorithm, which may be slow in the context of the semiparametric
      Cox model with incomplete covariate information. These estimating equations also
      lead to easily computable, direct estimators of standard errors, and thus
      overcome some of the difficulty in obtaining variance estimators based on the EM
      algorithm in this setting. We also develop an easily implemented goodness-of-fit
      procedure for Cox's regression model including haplotype effects. Finally, we
      apply the procedures presented in this article to investigate possible haplotype
      effects of the PAF-receptor on cardiovascular events in patients with coronary
      artery disease, and compare our results to those based on the EM algorithm.

PMID- 19764955
TI  - Segmentation and estimation for SNP microarrays: a Bayesian multiple change-point
      approach.
AB  - High-density single-nucleotide polymorphism (SNP) microarrays provide a useful
      tool for the detection of copy number variants (CNVs). The analysis of such large
      amounts of data is complicated, especially with regard to determining where copy
      numbers change and their corresponding values. In this article, we propose a
      Bayesian multiple change-point model (BMCP) for segmentation and estimation of
      SNP microarray data. Segmentation concerns separating a chromosome into regions
      of equal copy number differences between the sample of interest and some
      reference, and involves the detection of locations of copy number difference
      changes. Estimation concerns determining true copy number for each segment. Our
      approach not only gives posterior estimates for the parameters of interest,
      namely locations for copy number difference changes and true copy number
      estimates, but also useful confidence measures. In addition, our algorithm can
      segment multiple samples simultaneously, and infer both common and rare CNVs
      across individuals. Finally, for studies of CNVs in tumors, we incorporate an
      adjustment factor for signal attenuation due to tumor heterogeneity or normal
      contamination that can improve copy number estimates.

PMID- 19764973
TI  - Evaluation of different modes of combined therapy in children with
      monosymptomatic nocturnal enuresis.
AB  - OBJECTIVE: To evaluate the efficacy of different modes of combined therapy in
      children with monosymptomatic nocturnal enuresis (MNE). PATIENTS AND METHODS: A
      randomized prospective study was performed to compare the order of two types of
      combined therapy in children with MNE. Group A was treated with primary
      desmopressin treatment that was combined with alarm treatment after 3 months,
      while group B was treated with primary alarm treatment that was combined with
      desmopressin after 3 months. RESULTS: Within a period of 18 months, 43 previously
      untreated children fulfilled the inclusion criteria. Thirteen children achieved
      dryness after initial monotherapy or discontinued the study. Group A consisted of
      16 children and group B of 14 children. After the standardized treatment course
      of 6 months, 11/16 children in group A and 11/14 children in group B became dry
      (<3 wet nights/month). Altogether, 22/30 (73%) children were dry after combined
      treatment, consisting of 12/18 boys and 10/12 girls. Of the children with a
      normal maximum voided volume, 79% (19/24) achieved dryness, whereas only three of
      six children with small maximum voided volumes became dry. In all, 13/19 (68%)
      children with nocturnal polyuria and nine of 11 without nocturnal polyuria became
      dry. Only one child relapsed (group A). CONCLUSIONS: Combined therapy proved
      effective in children with MNE after 6 months, with no statistically significant
      differences between the two different orders of treatment.

PMID- 19764975
TI  - High-intensity focused ultrasound for localized prostate cancer: initial
      experience with a 2-year follow-up.

PMID- 19764976
TI  - Laparoscopic complete urinary tract extraction with the specimen withdrawn
      transvaginally.

PMID- 19764979
TI  - A continuous bladder neck-urethral anastomosis after open radical retropubic
      prostatectomy.

PMID- 19764982
TI  - Capsaicin affects brain function in a model of hepatic encephalopathy associated
      with fulminant hepatic failure in mice.
AB  - BACKGROUND AND PURPOSE: Hepatic encephalopathy is a neuropsychiatric syndrome
      caused by liver failure. In view of the effects of cannabinoids in a
      thioacetamide-induced model of hepatic encephalopathy and liver disease and the
      beneficial effect of capsaicin (a TRPV1 agonist) in liver disease, we assumed
      that capsaicin may also affect hepatic encephalopathy. EXPERIMENTAL APPROACH:
      Fulminant hepatic failure was induced in mice by thioacetamide and 24 h later,
      the animals were injected with one of the following compound(s): 2
      arachidonoylglycerol (CB(1), CB(2) and TRPV1 receptor agonist); HU308 (CB(2)
      receptor agonist), SR141716A (CB(1) receptor antagonist); SR141716A+2
      arachidonoylglycerol; SR144528 (CB(2) receptor antagonist); capsaicin; and
      capsazepine (TRPV1 receptor agonist and antagonist respectively). Their
      neurological effects were evaluated on the basis of activity in the open field,
      cognitive function in an eight-arm maze and a neurological severity score. The
      mice were killed 3 or 14 days after thioacetamide administration. 2
      arachidonoylglycerol and 5-hydroxytryptamine (5-HT) levels were determined by gas
      chromatography-mass spectrometry and high-performance liquid chromatography with
      electrochemical detection, respectively. RESULTS: Capsaicin had a neuroprotective
      effect in this animal model as shown by the neurological score, activity and
      cognitive function. The effect of capsaicin was blocked by capsazepine.
      Thioacetamide induced astrogliosis in the hippocampus and the cerebellum and
      raised brain 5-hydroxytryptamine levels, which were decreased by capsaicin,
      SR141716A and HU-308. Thioacetamide lowered brain 2-arachidonoylglycerol levels,
      an effect reversed by capsaicin. CONCLUSIONS: Capsaicin improved both liver and
      brain dysfunction caused by thioacetamide, suggesting that both the
      endocannabinoid and the vanilloid systems play important roles in hepatic
      encephalopathy. Modulation of these systems may have therapeutic value.

PMID- 19764984
TI  - Syndromic albinism and haemophagocytosis.

PMID- 19764985
TI  - JAK1 mutations are not frequent events in adult T-ALL: a GRAALL study.

PMID- 19764986
TI  - Rituximab therapy modulates IFN-gamma and IL-4 gene expression in a patient with
      acquired haemophilia A.

PMID- 19764983
TI  - Arginase: an emerging key player in the mammalian immune system.
AB  - The enzyme arginase metabolizes L-arginine to L-ornithine and urea. Besides its
      fundamental role in the hepatic urea cycle, arginase is also expressed the immune
      system of mice and man. While significant interspecies differences exist
      regarding expression, subcellular localization and regulation of immune cell
      arginase, associated pathways of immunopathology are comparable between species.
      Arginase is induced in murine myeloid cells mainly by Th2 cytokines and
      inflammatory agents and participates in a variety of inflammatory diseases by
      down-regulation of nitric oxide synthesis, induction of fibrosis and tissue
      regeneration. In humans, arginase I is constitutively expressed in
      polymorphonuclear neutrophils and is liberated during inflammation. Myeloid cell
      arginase-mediated L-arginine depletion profoundly suppresses T cell immune
      responses and this has emerged as a fundamental mechanism of inflammation
      associated immunosuppression. Pharmacological interference with L-arginine
      metabolism is a novel promising strategy in the treatment of cancer, autoimmunity
      or unwanted immune deviation.

PMID- 19764987
TI  - 15-deoxy-Delta(12,14)-PGJ(2) induces cell cycle arrest and apoptosis of
      haematopoietic progenitors.

PMID- 19764988
TI  - Efficacy and safety of deferasirox doses of >30 mg/kg per d in patients with
      transfusion-dependent anaemia and iron overload.
AB  - The highest approved dose of deferasirox is currently 30 mg/kg per d in many
      countries; however, some patients require escalation above 30 mg/kg per d to
      achieve their therapeutic goals. This retrospective analysis investigated the
      efficacy (based on change in serum ferritin levels) and safety of deferasirox >30
      mg/kg per d in adult and paediatric patients with transfusion-dependent anaemias,
      including beta-thalassaemia, sickle cell disease and the myelodysplastic
      syndromes. In total, 264 patients pooled from four clinical trials received doses
      of >30 mg/kg per d; median exposure to deferasirox >30 mg/kg per d was 36 weeks.
      In the overall population there was a statistically significant median decrease
      in serum ferritin of 440 microg/l (P < 0.0001) from pre-dose-escalation to the
      time-of-analysis; significant decreases were also observed in adult and
      paediatric patients, as well as beta-thalassaemia patients. The adverse event
      profile in patients who received deferasirox doses of >30 mg/kg per d was
      consistent with previously published data. There was no worsening of renal or
      liver function following dose escalation. Deferasirox >30 mg/kg per d effectively
      reduced iron burden to levels lower than those achieved prior to dose escalation
      in patients with transfusion-dependent anaemias. This has important implications
      for patients who are heavily transfused and may require higher doses to reduce
      body iron burden.

PMID- 19764989
TI  - Daily labile plasma iron as an indicator of chelator activity in Thalassaemia
      major patients.
AB  - Labile plasma iron (LPI), a non-transferrin-bound component of plasma iron
      detected in iron overload disorders is a potential source of cellular iron
      accumulation and ensuing oxidative damage. Periodic monitoring of LPI over a 24 h
      time-span was used to compare the ability of chelation to control daily LPI
      levels in 40 Thalassaemia major patients (9-11/group) who had been receiving one
      of three different chelation protocols for more than a year: Group I.
      deferrioxamine overnight, Group II. deferiprone daily, Group III. deferrioxamine
      and deferiprone sequentially. An additional group (Group IV) was treated with
      desferasirox for up to 6 months. The patterns of daily LPI recrudescence showed
      significant individual variations, especially in patients treated with
      deferrioxamine or deferiprone, although these patterns were maintained over 6-9
      months of treatment in all groups. Group data analysis showed that the proportion
      of patients whose daily LPI were maintained within the normal range (<0.45
      micromol/l) varied with treatment: 6/10 with deferrioxamine, 5/11 with
      deferiprone, 9/10 with deferrioxamine + deferiprone and 8/10 at the onset and
      10/10 after 6 months treatment with deferasirox. Although the clinical
      significance and therapeutic value of LPI remain to be established, monitoring of
      daily LPI level may provide an analytical basis for assessing chelation efficacy
      in preventing daily LPI recrudescence.

PMID- 19764990
TI  - ATG-saporin-S6 immunotoxin: a new potent and selective drug to eliminate
      activated lymphocytes and lymphoma cells.
AB  - Anti-thymocyte globulins (ATG) are currently used to prevent graft-versus-host
      disease in haematopoietic stem cell transplants from alternative donors and to
      treat and prevent acute organ rejection after transplantation. Many recent
      studies have demonstrated that ATG can also be beneficial in patients with
      myeloma, lymphoma, leukaemia and myelodysplastic syndrome. This study showed, for
      the first time, that the cytotoxic effect of ATG can been enhanced by conjugation
      with saporin-S6, which is one of the most stable and active type-1 ribosome
      inactivating proteins. The ATG-saporin-S6 immunotoxin showed a strong cytotoxic
      effect on five lymphoma- and leukaemia-derived cell lines as well as on activated
      lymphocytes while sparing non-haematological cell lines. ATG-saporin-S6 induced a
      time-dependent activation of caspase-3/7 in RAJI cells. The caspase inhibitor Z
      VAD-fmk partially rescued the cells that were treated with ATG-saporin-S6,
      suggesting that multiple cell death pathways, some of which are caspase
      independent, play a role in ATG-saporin-S6 toxicity. In our experiments ATG
      increased the complement-independent cytotoxicity of activated lymphocytes by a
      magnitude of 3-5 logs after conjugation. These findings suggest that the ATG
      saporin-S6 immunotoxin is a promising therapeutic tool for many pathological
      conditions involving T lymphocytes and T and B neoplastic cells.

PMID- 19764991
TI  - Impaired pneumococcal immunity in children after treatment for acute
      lymphoblastic leukaemia.
AB  - Although the substantial risk for invasive pneumococcal disease is well
      recognized in children after allogeneic stem cell transplantation, little is
      known about the specific immunity against pneumococci in children after cytotoxic
      therapy for acute lymphoblastic leukaemia (ALL). We therefore assessed the
      spontaneous reconstitution of humoral immunity against pneumococcal antigens, of
      total IgG and the IgG2 subclass, and of lymphocyte subsets in a total of 53
      children treated for ALL. None of the patients had received pneumococcal
      vaccination prior to or after therapy for ALL. At 3 and 9 months after completion
      of chemotherapy, most patients had levels of specific antibodies to pneumococcal
      antigens below the presumed threshold of protection and significantly lower than
      those of age-matched unvaccinated healthy controls. In contrast, at 9 months
      after completion of therapy, only a minority of patients had immunoglobulin
      concentrations or lymphocyte subset counts below the age-matched reference value.
      Our data indicate that patients with ALL who are unvaccinated against pneumococci
      have a selective immunodeficiency with an impaired antibody protection against
      pneumococci for up to 9 months after completion of therapy. Therefore, effective
      prevention, including chemoprophylaxis and active immunization, has to be
      considered in this patient population.

PMID- 19764992
TI  - Impaired up-regulation of polo-like kinase 2 in B-cell chronic lymphocytic
      leukaemia lymphocytes resistant to fludarabine and 2-chlorodeoxyadenosine: a
      potential marker of defective damage response.
AB  - The functional evaluation of ataxia telangiectasia mutated (ATM) and p53 was
      recently developed in B-cell chronic lymphocytic leukaemia (B-CLL), a disease in
      which the response to DNA damage is frequently altered. We identified a novel
      biomarker of chemosensitivity based on the induction of DNA damage by the purine
      nucleoside analogues (PNA) fludarabine and 2-chlorodeoxyadenosine (CdA). Using
      genome-wide expression profiling, it was observed that, in chemosensitive
      samples, PNA predominantly increased the expression of p53-dependent genes, among
      which PLK2 was the most highly activated at early time points. Conversely, in
      chemoresistant samples, p53-dependent and PLK2 responses were abolished. Using a
      quantitative real time polymerase chain reaction, we confirmed that PNA dose- and
      time-dependently increased PLK2 expression in chemosensitive but not
      chemoresistant B-CLL samples. Analysis of a larger cohort of B-CLL patients
      showed that cytotoxicity induced by PNA correlated well with PLK2 mRNA induction.
      Interestingly, we observed that failure to up-regulate PLK2 following PNA and
      chemoresistance were not strictly correlated with structural alterations in the
      TP53 gene. In conclusion, we propose that testing PLK2 activation after a 24-h
      incubation with PNA could be used to investigate the functional integrity of DNA
      damage-response pathways in B-CLL cells, and predict clinical sensitivity to
      these drugs.

PMID- 19764993
TI  - Male breast carcinoma with zosteriform metastasis.

PMID- 19764994
TI  - Breast cancer subtypes as defined by the estrogen receptor (ER), progesterone
      receptor (PR), and the human epidermal growth factor receptor 2 (HER2) among
      women with invasive breast cancer in California, 1999-2004.
AB  - Breast cancer research examining either molecular profiles or biomarker subtypes
      has focused on the estrogen receptor negative/progesterone receptor
      negative/human epidermal growth factor receptor 2 negative (ER-/PR-/HER2-) and ER
      /PR-/HER2+ subtypes. Less is known about the epidemiology or clinical outcome of
      the other subtypes. This study examines the eight combinations of ER/PR/HER2 in
      patients with invasive breast cancer. The 5-year relative survival and the
      distribution among demographic, socioeconomic, and tumor characteristics of each
      of the subtypes are examined. Using the California Cancer Registry, 61,309 women
      with primary invasive breast cancer were classified according to ER/PR/HER2
      status. Five-year relative survival was computed for the eight subtypes.
      Bivariate analyses were used to assess the distribution of cases across all
      subtypes. Multivariate logistic regression was used to compute the adjusted odds
      of having one of the five subtypes with the best and worst survival. Survival
      varied from 96% (ER+/PR+/HER2-) to 76% (ER-/PR-/HER2+ and ER-/PR-/HER2-). The
      four subtypes with the poorest survival were all ER negative. Women who were
      younger than age 50, non-Hispanic black or Hispanic, of the lowest SES groups,
      and had stage IV tumors that were undifferentiated were overrepresented in ER-/PR
      /HER2+ and triple negative (ER-/PR-/HER2-) subtypes. Asian Pacific Islanders had
      increased odds (OR = 1.41; 95% confidence interval [CI] = 1.26-1.57) of having
      the ER-/PR-/HER2+ subtype. Stage III tumors (OR = 1.25; 95% CI = 1.08-1.44) and
      stage IV tumors (OR = 1.58; 95% CI = 1.27-1.98) had higher odds than stage I
      tumors of being ER-/PR-/HER2+. Stage IV tumors (OR = 0.54; 95% CI = 0.44-0.67)
      strongly decreased the odds of the ER-/PR-/HER2- subtype. Poorly differentiated
      and undifferentiated tumors were over 20 times as likely as well-differentiated
      tumors of being ER-/PR-/HER2- or ER-/PR-/HER2+. There are considerable
      differences in survival, demographics, and tumor characteristics among the eight
      subtypes. We recommend reporting breast cancer as an ER/PR/HER2 subtype and
      precisely documenting demographic and tumor characteristics.

PMID- 19764996
TI  - Synergistic antiproliferative effect of mTOR inhibitors in combination with 5
      fluorouracil in scirrhous gastric cancer.
AB  - The aim of this study is to clarify the benefit of combination chemotherapy in
      gastric cancer based on a cell-signal inhibitor and an anticancer drug. Two
      scirrhous gastric cancer cell lines and two non-scirrhous gastric cancer cell
      lines were used. Five anticancer drugs (5-fluorouracil [5FU], paclitaxel,
      oxaliplatin, irinotecan, and gemcitabine) and four cell-signal inhibitors,
      mammalian target of rapamycin (mTOR) inhibitor, glycogen synthase kinase 3beta,
      p38alphabetaMAPK, and cyclin-dependent kinase, were used. The proliferation of
      cancer cells was examined by MTT assay and in vivo study. The apoptosis of cancer
      cells and the expression of apoptosis-related molecules were examined by flow
      cytometry, real-time PCR, and immunostaining. mTOR inhibitors with 5FU showed a
      synergistic antiproliferative effect in scirrhous gastric cancer, whereas the
      other signal inhibitors showed no synergistic effect with any anticancer drugs.
      mTOR inhibitor decreased the IC(50) of 5FU and increased the apoptosis rate in
      scirrhous gastric cancer cells, but not in non-scirrhous gastric cancer cells.
      The pan-caspase inhibitor, zVAD-fmk, inhibits apoptosis induced in combination
      with 5FU and mTOR inhibitor. mTOR inhibitor decreased dihydropyrimidine
      dehydrogenase, thymidylatesynthase, and bcl-2 expression, and increased caspase-3
      and p21 expression of scirrhous gastric cancer cells, but did not affect those of
      non-scirrhous gastric cancer cells. In an in vivo study, mTOR inhibitor
      significantly enhanced the therapeutic efficacy of S1, an analog of 5FU. These
      findings suggest that mTOR inhibitor interacts with 5FU in a synergistic manner
      in scirrhous gastric cancer cells by the activation of the apoptosis signal.
      Therefore, mTOR inhibitor is a promising therapeutic agent in combination with
      5FU in scirrhous gastric cancer.

PMID- 19764997
TI  - Association of TP53 and MDM2 polymorphisms with survival in bladder cancer
      patients treated with chemoradiotherapy.
AB  - Platinum-based chemoradiotherapy (CRT) as bladder conservation therapy has shown
      promising results for muscle-invasive bladder cancer. However, CRT might diminish
      survival as a result of the delay in cystectomy for some patients with non
      responding bladder tumors. Because the p53 tumor suppression pathway, including
      its MDM2 counterpart, is important in chemotherapy- and radiotherapy-associated
      effects, functional polymorphisms in the TP53 and MDM2 genes could influence the
      response to treatment and the prognosis following CRT. We investigated
      associations between two such polymorphisms, and p53 overexpression, and response
      or survival in bladder cancer patients treated with CRT. The study group
      comprised 96 patients who underwent CRT for transitional cell carcinoma of the
      bladder. Single nucleotide polymorphisms (SNPs) in TP53 (codon 72, arginine >
      proline) and MDM2 (SNP309, T > G) were genotyped using PCR-RFLP, and nuclear
      expression levels of p53 were examined using immunohistochemistry. None of the
      genotypes or p53 overexpression was significantly associated with response to
      CRT. However, patients with MDM2 T / G + G / G genotypes had improved cancer
      specific survival rates after CRT (P = 0.009). In multivariate analysis, the MDM2
      T / G + G / G genotypes, and more than two of total variant alleles in TP53 and
      MDM2, were independently associated with improved cancer-specific survival (P =
      0.031 and P = 0.015, respectively). In addition, MDM2 genotypes were
      significantly associated with cystectomy-free survival (P = 0.030). These results
      suggest that the TP53 and MDM2 genotypes might be useful prognostic factors
      following CRT in bladder cancer, helping patient selection for bladder
      conservation therapy.

PMID- 19764998
TI  - Down-regulation of pescadillo inhibits proliferation and tumorigenicity of breast
      cancer cells.
AB  - Pescadillo, which has been found to be involved in the process of ribosomal
      biogenesis, has been demonstrated to play a role in embryonic development, DNA
      replication, and gene transcription. While deregulation of ribosomal biogenesis
      was also found to contribute to carcinogenesis, and proteins that regulate
      ribosomal biogenesis are commonly overexpressed in primary tumors, little is
      known about the clinical significance and biological function of pescadillo in
      human breast cancer. In the current study, we found that the expression of
      pescadillo was markedly up-regulated in human breast cancer cells and tissues at
      both mRNA and protein levels. Immunohistochemical analysis revealed that
      pescadillo expression in clinical stage I-IV primary breast cancer tissues was
      statistically significantly higher than that in normal breast tissues (P < 0.05).
      Furthermore, we demonstrated that knockdown pescadillo with RNAis inhibited cell
      proliferation and the colony-forming ability of the cells. Anchorage-independent
      growth ability assay indicated that ablation of pescadillo led to the reduction
      of breast cancer cells tumorigenicity in vitro. Moreover, depletion of endogenous
      pescadillo resulted in decreased expression of cell cycle protein cyclin D1 and
      up-regulation of cyclin-dependent kinase inhibitor p27(Kip1), as well as
      attenuated protein kinase B (Akt)/glycogen synthase kinase 3 beta (GSK-3beta)
      signaling. Taken together, our results suggest that pescadillo might play a role
      in promoting the proliferation and carcinogenesis of human breast cancer, and
      thereby might be a potential target for human breast cancer treatment.

PMID- 19764999
TI  - Different histological types of non-small cell lung cancer have distinct folate
      and DNA methylation levels.
AB  - Aberrant DNA methylation is a commonly observed epigenetic change in lung cancer.
      Folate has been suggested to play a role in the homeostasis of DNA methylation
      and has also been implicated in cancer chemotherapy. We investigated a possible
      role for folate in DNA methylation by measuring folate concentrations in tumors
      and adjacent normal tissues from 72 non-small cell lung cancer (NSCLC) patients.
      These were compared to DNA methylation levels and to clinicopathological
      features. Folate concentrations were determined as the sum of 5,10
      methylenetetrahydrofolate and tetrahydrofolate. The MethyLight assay was used to
      quantitate methylation in promoter regions of P16(CDKN2A), APC, CDH13, RARB,
      RASSF1, RUNX3, and MYOD1. Methylation of LINE-1 repeats was used as a surrogate
      for global methylation. Folate levels in tumors correlated positively with LINE
      1, CDH13, and RUNX3 methylation. Folate concentrations and methylation of LINE-1,
      RASSF1, and RUNX3 were significantly higher in adenocarcinoma compared to
      squamous cell carcinoma (SCC). Two sets of array-based data retrieved from the
      Gene Expression Omnibus consistently showed that expression of FOLR1, a folate
      transport enzyme, and GGH, an enzyme that prevents folate retention, were higher
      and lower, respectively, in adenocarcinomas compared to SCC. This was
      independently validated by quantitative RT-PCR in 26 adenocarcinomas and 13 SCC.
      Our results suggest that folate metabolism plays a role in aberrant DNA
      methylation in NSCLC. The histological subtype differences in folate
      concentration and DNA methylation observed here were associated with distinct
      expression patterns for folate metabolizing enzymes. These findings may have
      clinical applications for histology-directed chemotherapy with fluoropyrimidine
      and anti-folates in NSCLC.

PMID- 19765000
TI  - Analysis of IDH1 and IDH2 mutations in Japanese glioma patients.
AB  - A recent study reported on mutations in the active site of the isocitrate
      dehydrogenase 1 (IDH1) gene in several types of gliomas. All mutations detected
      resulted in an amino acid exchange at position 132. We analyzed the genomic
      region spanning wild-type R132 of IDH1 by direct sequencing in 125 glial tumors.
      A total of 39 IDH1 mutations were observed. Mutations of the IDH2 gene,
      homologous to IDH1, were often detected in gliomas without IDH1 mutations. In the
      present study, R172 mutation of the IDH2 gene was detected in one anaplastic
      astrocytoma. IDH1 or IDH2 mutations were frequently in oligodendrogliomas (67%),
      anaplastic astrocytomas (62%), anaplastic oligoastrocytomas (75%), anaplastic
      oligodendrogliomas (50%), secondary glioblastomas (67%), gangliogliomas (38%),
      and anaplastic gangliogliomas (60%). Primary glioblastomas were characterized by
      a low frequency of mutations (5%) at amino acid position 132 of IDH1. Mutations
      of the IDH1 or IDH2 genes were significantly associated with improved outcome in
      patients with anaplastic astrocytomas. Our data suggest that IDH1 or IDH2
      mutation plays a role in early tumor progression of several types of glioma and
      might arise from a common glial precursor. The infrequency of IDH1 mutation in
      primary glioblastomas revealed that these subtypes are genetically distinct
      entities from other glial tumors.

PMID- 19765002
TI  - Memory binding in early childhood: evidence for a retrieval deficit.
AB  - Previous research has suggested that performance for items requiring memory
      binding processes improves between ages 4 and 6 (J. Sluzenski, N. Newcombe, & S.
      L. Kovacs, 2006). The present study suggests that much of this improvement is due
      to retrieval, as opposed to encoding, deficits for 4-year-olds. Four- and 6-year
      old children (N = 48 per age) were given objects, backgrounds, and object +
      background combinations to remember. Younger children performed equivalently to 6
      year-olds during a working memory task for all types of memory questions but were
      impaired during a long-term memory task for the object + background combinations.
      Furthermore, this deficit was completely due to differences in false alarm rates,
      suggesting that separate analyses of hits and false alarms may be preferable to
      corrected recognition scores when studying memory development.

PMID- 19765003
TI  - Does higher quality early child care promote low-income children's math and
      reading achievement in middle childhood?
AB  - Higher quality child care during infancy and early childhood (6-54 months of age)
      was examined as a moderator of associations between family economic status and
      children's (N = 1,364) math and reading achievement in middle childhood (4.5-11
      years of age). Low income was less strongly predictive of underachievement for
      children who had been in higher quality care than for those who had not.
      Consistent with a cognitive advantage hypothesis, higher quality care appeared to
      promote achievement indirectly via early school readiness skills. Family
      characteristics associated with selection into child care also appeared to
      promote the achievement of low-income children, but the moderating effect of
      higher quality care per se remained evident when controlling for selection using
      covariates and propensity scores.

PMID- 19765004
TI  - The impact of background television on parent-child interaction.
AB  - This study investigated the hypothesis that background television affects
      interactions between parents and very young children. Fifty-one 12-, 24-, and 36
      month-old children, each accompanied by 1 parent, were observed for 1 hr of free
      play in a laboratory space resembling a family room. For half of the hour, an
      adult-directed television program played in the background on a monaural
      television set. During the other half hour, the television was not on. Both the
      quantity and quality of parent-child interaction decreased in the presence of
      background television. These findings suggest one way in which early, chronic
      exposure to television may have a negative impact on development.

PMID- 19765005
TI  - Live action: can young children learn verbs from video?
AB  - The availability of educational programming aimed at infants and toddlers is
      increasing, yet the effect of video on language acquisition remains unclear.
      Three studies of 96 children aged 30-42 months investigated their ability to
      learn verbs from video. Study 1 asked whether children could learn verbs from
      video when supported by live social interaction. Study 2 tested whether children
      could learn verbs from video alone. Study 3 clarified whether the benefits of
      social interaction remained when the experimenter was shown on a video screen
      rather than in person. Results suggest that younger children only learn verbs
      from video with live social interaction whereas older children can learn verbs
      from video alone. Implications for verb learning and educational media are
      discussed.

PMID- 19765006
TI  - Three randomized controlled trials of early long-chain polyunsaturated Fatty Acid
      supplementation on means-end problem solving in 9-month-olds.
AB  - This study examines whether feeding infants formula supplemented with long-chain
      polyunsaturated fatty acids (LCPUFA) improves cognitive function of 9-month-olds.
      Participants included 229 infants from 3 randomized controlled trials. Children
      received either formula supplemented with docosahexaenoic acid and arachidonic
      acid, or a control formula beginning at 1-5 days (12-month feeding study), or
      following 6 weeks (6-week-weaning study) or 4-6 months of breastfeeding (4-to 6
      month weaning study). Infants were assessed with a 2-step problem solving task.
      In the 12-month feeding and 6-week weaning studies, supplemented children had
      more intentional solutions (successful task completions) and higher intention
      scores (goal-directed behaviors) than controls. These results suggest that LCPUFA
      supplementation improves means-end problem solving.

PMID- 19765007
TI  - Trajectories of physical discipline: early childhood antecedents and
      developmental outcomes.
AB  - This study examined childhood antecedents and developmental outcomes associated
      with trajectories of mild and harsh parental physical discipline. Interview,
      questionnaire, and observational data were available from 499 children followed
      from ages 5 to 16 and from 258 children in an independent sample followed from
      ages 5 to 15. Analyses indicated distinct physical discipline trajectory groups
      that varied in frequency of physical discipline and rate of change. In both
      samples, family ecological disadvantage differentiated the trajectory groups; in
      the first sample, early child externalizing also differentiated the groups.
      Controlling for early childhood externalizing, the minimal/ceasing trajectory
      groups were associated with the lowest levels of subsequent adolescent antisocial
      behavior in both samples and with parent-adolescent positive relationship quality
      in the second sample.

PMID- 19765008
TI  - Correlates and consequences of spanking and verbal punishment for low-income
      white, african american, and mexican american toddlers.
AB  - This study examined the prevalence, predictors, and outcomes of spanking and
      verbal punishment in 2,573 low-income White, African American, and Mexican
      American toddlers at ages 1, 2, and 3. Both spanking and verbal punishment varied
      by maternal race/ethnicity. Child fussiness at age 1 predicted spanking and
      verbal punishment at all 3 ages. Cross-lagged path analyses indicated that
      spanking (but not verbal punishment) at age 1 predicted child aggressive behavior
      problems at age 2 and lower Bayley mental development scores at age 3. Neither
      child aggressive behavior problems nor Bayley scores predicted later spanking or
      verbal punishment. In some instances, maternal race/ethnicity and/or emotional
      responsiveness moderated the effects of spanking and verbal punishment on child
      outcomes.

PMID- 19765009
TI  - Faces do not capture special attention in children with autism spectrum disorder:
      a change blindness study.
AB  - Two experiments investigated attention of children with autism spectrum disorder
      (ASD) to faces and objects. In both experiments, children (7- to 15-year-olds)
      detected the difference between 2 visual scenes. Results in Experiment 1 revealed
      that typically developing children (n = 16) detected the change in faces faster
      than in objects, whereas children with ASD (n = 16) were equally fast in
      detecting changes in faces and objects. These results were replicated in
      Experiment 2 (n = 16 in children with ASD and 22 in typically developing
      children), which does not require face recognition skill. Results suggest that
      children with ASD lack an attentional bias toward others' faces, which could
      contribute to their atypical social orienting.

PMID- 19765010
TI  - The development of emotion recognition in individuals with autism.
AB  - Emotion recognition was investigated in typically developing individuals and
      individuals with autism. Experiment 1 tested children (5-7 years, n = 37) with
      brief video displays of facial expressions that varied in subtlety. Children with
      autism performed worse than the control children. In Experiment 2, 3 age groups
      (8-12 years, n = 49; 13-17 years, n = 49; and adults n = 45) were tested on the
      same stimuli. Whereas the performance of control individuals was best in the
      adult group, the performance of individuals with autism was similar in all age
      groups. Results are discussed with respect to underlying cognitive processes that
      may be affecting the development of emotion recognition in individuals with
      autism.

PMID- 19765011
TI  - The influence of representations of attachment, maternal-adolescent relationship
      quality, and maternal monitoring on adolescent substance use: a 2-year
      longitudinal examination.
AB  - The present study examined the hypotheses that more secure representations of
      attachments to parents are associated with less adolescent substance use over
      time and that this link is mediated through relationship quality and monitoring.
      A sample of 200 adolescents (M = 14-16 years), their mothers, and close friends
      were assessed over 2 years. Higher levels of security in attachment styles, but
      not states of mind, were predictive of higher levels of monitoring and support
      and lower levels of negative interactions. Higher levels of security in
      attachment styles had an indirect effect on changes in substance use over time,
      mediated by maternal monitoring. These findings highlight the roles of
      representations of attachments, mother-adolescent relationship qualities, and
      monitoring in the development of adolescent substance use.

PMID- 19765012
TI  - Associations between father absence and age of first sexual intercourse.
AB  - Children raised without a biological father in the household have earlier average
      ages of first sexual intercourse than children raised in father-present
      households. Competing theoretical perspectives have attributed this either to
      effects of father absence on socialization and physical maturation or to
      nonrandom selection of children predisposed for early sexual intercourse into
      father-absent households. Genetically informative analyses of the children of
      sister dyads (N = 1,382, aged 14-21 years) support the selection hypothesis: This
      association seems attributable to confounded risks, most likely genetic in
      origin, which correlated both with likelihood of father absence and early sexual
      behavior. This holds implications for environmental theories of maturation and
      suggests that previous research may have inadvertently overestimated the role of
      family structure in reproductive maturation.

PMID- 19765013
TI  - Disclosure to parents about everyday activities among american adolescents from
      mexican, chinese, and European backgrounds.
AB  - Disclosure to parents and reasons for not disclosing different activities were
      examined in 489 Chinese, Mexican, and European American adolescents (M = 16.37
      years, SD = 0.77). With generational status controlled, Chinese American
      adolescents disclosed less to mothers about personal and multifaceted activities
      than European Americans and less about personal feelings than other youth,
      primarily because these acts were considered personal, not harmful, or because
      parents would not listen or understand. Disclosure regarding prudential behavior
      was lower among Mexican American than among European American adolescents,
      primarily due to concerns with parental disapproval. Multigroup path analyses
      indicated that greater closeness to parents is associated with more disclosure
      for all youth and activities; associations between family obligation and
      disclosure varied by domain and ethnicity.

PMID- 19765014
TI  - Shyness-sensitivity and social, school, and psychological adjustment in rural
      migrant and urban children in china.
AB  - The purpose of this study was to examine relations between shyness-sensitivity
      and social competence, school performance, and psychological well-being in
      Chinese children with rural and urban backgrounds. Participants were students in
      rural migrant children schools and city schools in China (Ns = 411 and 518,
      respectively; M age = 10 years). Data were obtained from peer evaluations,
      teacher ratings, self-reports, and school records. It was found that shyness was
      associated with social and school problems and depression in urban children.
      However, shyness was generally associated with indexes of adjustment such as
      leadership, teacher-rated competence, and academic achievement in rural migrant
      children. The results indicate the role of context in defining the functional
      meaning of social behavior in children's adjustment.

PMID- 19765015
TI  - The influence of student perceptions of school climate on socioemotional and
      academic adjustment: a comparison of chinese and american adolescents.
AB  - This study explored students' perceptions of 3 dimensions of school climate
      (teacher support, student-student support, and opportunities for autonomy in the
      classroom) and the associations between these dimensions and adolescent
      psychological and academic adjustment in China and the United States. Data were
      drawn from 2 studies involving 706 middle school students (M = 12.26) from
      Nanjing, China, and 709 middle school students (M = 12.36) from New York City.
      Findings revealed that students in China perceived higher levels of teacher
      support, student-student support, and opportunities for autonomy in the classroom
      than students in the United States. Furthermore, students' perceptions of teacher
      support and student-student support were positively associated with adolescents'
      self-esteem and grade point average but negatively associated with depressive
      symptoms for both Chinese and American adolescents.

PMID- 19765016
TI  - Adolescent gender-role identity and mental health: gender intensification
      revisited.
AB  - Gender intensification, an increased pressure for adolescents to conform to
      culturally sanctioned gender roles, has been posited as an explanation for the
      emergence of the gender difference in depression. This longitudinal study
      assessed whether 410 individuals became more stereotypical in their gender-role
      identity across adolescence and whether such patterns predicted depressive
      symptoms. Girls reported higher femininity than boys at ages 11, 13, and 15, but
      girls and boys did not differ in masculinity. Contrary to prevailing views, there
      was not evidence of intensification in femininity or masculinity. Positive
      trajectories in masculinity for both girls and boys predicted fewer depressive
      symptoms, particularly at moderate levels of stress. Findings suggest a need to
      reconceptualize gender intensification in ways that characterize contemporary
      adolescence.

PMID- 19765017
TI  - Measuring growth in bilingual and monolingual children's english productive
      vocabulary development: the utility of combining parent and teacher report.
AB  - This longitudinal study examined growth in the English productive vocabularies of
      bilingual and monolingual children between ages 24 and 36 months and explored the
      utility and validity of supplementing parent reports with teacher reports to
      improve the estimation of children's vocabulary. Low-income, English-speaking and
      English/Spanish-speaking parents and Early Head Start and Head Start program
      teachers completed the MacArthur-Bates Communicative Development Inventory, Words
      and Sentences for 85 children. Results indicate faster growth rates for
      monolingual than for bilingual children and larger vocabularies for bilingual
      children who spoke mostly English than mostly Spanish at home. Parent-teacher
      composite reports, like parent reports, significantly related to children's
      directly assessed productive vocabulary at ages 30 and 36 months, but parent
      reports fit the model better. Implications for vocabulary assessment are
      discussed.

PMID- 19765018
TI  - Associations between social understanding, sibling relationship quality, and
      siblings' conflict strategies and outcomes.
AB  - Sibling relationship quality and social understanding (second-order false belief,
      conflict interpretation, and narrative conflict perspective references) were
      examined as unique and interactive correlates of sibling conflict behavior in 62
      dyads (older M age = 8.39 years and younger M age = 6.06 years). High-quality
      relationships were associated with positive conflict processes. Younger siblings'
      second-order false belief scores were negatively associated with constructive
      conflict strategies, and older siblings' narrative self-referential focus was
      negatively associated with compromise. Associations between younger children's
      social understanding (conflict interpretation and narrative perspective
      references) and siblings' dyadic conflict behavior were moderated by relationship
      quality. Results suggest that links between social understanding and conflict
      behavior should be considered in conjunction with the quality of children's
      relationships.

PMID- 19765021
TI  - Three clonal types of urothelium with different capacities for replication.
AB  - OBJECTIVES: Similar to other epithelia, urothelium in vivo has a hierarchal
      organization of cells each with specific gradients of differentiation. While
      distinct cell types have been described as important in bladder cancer in vitro,
      clonal and proliferative capacities of normal urothelial cells have not been
      characterized. MATERIALS AND METHODS: Three cell types and colony types were
      identified from primary porcine urothelial culture. Proliferative activity,
      patterns of apoptosis and differentiation, colony forming efficiency and ability
      to change phenotype with passage were determined and compared. RESULTS: Small, T
      I colonies with large flattened (type-1) cells had low levels of proliferation
      and high levels of apoptosis. Large T-III colonies had a central area of small
      (type-3) cells surrounded by type-1 and type-2 cells. Proliferation and apoptosis
      were asymmetrically distributed in the periphery of T-II and T-III colonies. T
      III colonies proved to be significantly more clonogenic and proliferative. With
      appropriate induction, type-1 cells were able to proliferate upon passage and
      form type-3 cells, yet long-term culture demonstrated that progeny of type-1
      cells appeared to have inherited a clonogenic handicap. CONCLUSIONS: Type-3 cells
      in the centre of T-III colonies appear to harbour stem-like qualities with a
      relatively low proliferative and apoptotic index at homeostasis and the ability
      to become highly proliferative upon passage. This study demonstrates that
      distinct urothelial cell types with differing clonal capacities can be isolated
      from the bladder and these cells may have implications for tissue engineering and
      carcinogenesis.

PMID- 19765020
TI  - Minimal persistent inflammation in allergic rhinitis: implications for current
      treatment strategies.
AB  - Patients with allergic rhinitis have traditionally been placed into 'seasonal'
      and 'perennial' categories, which do not account for the subclinical inflammatory
      state that exists in many patients. In subjects with seasonal and perennial
      allergic rhinitis, even subthreshold doses of allergen have been found to cause
      inflammatory cell infiltration in the nasal mucosa, including increases in
      expression of cellular adhesion molecules, nasal and conjunctival eosinophilia,
      and other markers of inflammation, which do not result in overt allergy symptoms.
      This state - which has been termed 'minimal persistent inflammation'- may
      contribute to hyperreactivity and increased susceptibility to development of
      clinical symptoms as well as common co-morbidities of allergic rhinitis, such as
      asthma. Treating overt allergy symptoms as well as this underlying inflammatory
      state requires agents that have well-established clinical efficacy, convenient
      administration, potent anti-inflammatory effects and proven long-term safety, so
      that long-term continuous administration is feasible. Of the three major classes
      of commonly used allergic rhinitis medications - intranasal corticosteroids, anti
      histamines, and anti-leukotrienes - intranasal corticosteroids appear to
      represent the most reasonable therapeutic option in patients who would benefit
      from continuous inhibition of persistent inflammation.

PMID- 19765024
TI  - Are we missing the boat? Collaborative solutions for North American fish wars.

PMID- 19765022
TI  - Occurrence of macrolide-resistant Mycoplasma pneumoniae strains in Germany.
AB  - In a total of 167 respiratory tract specimens from adult outpatients with
      confirmed Mycoplasma pneumoniae pneumonia, sampled between 2003 and 2008, and a
      further 99 isolates obtained from patients between 1991 and 2009 in Germany, M.
      pneumoniae was tested for macrolide resistance. Using PCR, real-time PCR and
      sequencing of the 23S rRNA gene, 1.2% of M. pneumoniae in the respiratory tract
      samples and 3.0% of the isolates were found to be resistant. The results indicate
      a limited but not negligible importance of macrolide-resistant M. pneumoniae in
      the population investigated, which requires the monitoring of macrolide
      susceptibility of isolates or the testing of respiratory samples by molecular
      methods.

PMID- 19765025
TI  - Brazil should facilitate research permits.

PMID- 19765026
TI  - 110 most important questions.

PMID- 19765027
TI  - Two cultures of conservation.

PMID- 19765029
TI  - Practicing fisheries conservation biology within harvesting regimes.

PMID- 19765031
TI  - Sedentarization of Tibetan nomads.

PMID- 19765032
TI  - Conservation and aid: designing more effective investments in natural resource
      governance reform.
AB  - Biodiversity conservation outcomes are closely related to the rules and
      institutions governing resource use. Creating local incentives for conservation
      through more secure resource tenure is central to conservation outcomes on
      private and communal lands, where the preponderance of biodiversity occurs.
      Conservation efforts in sub-Saharan Africa are therefore centrally concerned with
      governance dynamics and institutional reform processes, such as the
      decentralization of property rights, and how best to achieve such reforms.
      Traditional mechanisms for financing conservation efforts in Africa rely heavily
      on funds channeled through multilateral and bilateral aid agencies. The history
      of development aid highlights a range of constraints these aid agencies face in
      terms of working toward more effective resource governance arrangements and
      promoting reforms. Government aid agencies possess incentives for promoting large
      scale and short-term projects that maximize expenditure volumes and tend to
      define issues in technical rather than political terms. The history of
      development aid suggests that these and other characteristics of aid agencies
      impedes their ability to influence governance reform processes and that aid
      funding may discourage the adoption of reforms. Greater emphasis in African
      conservation financing needs to be placed on flexible, small-scale investments
      aligned to local interests and constituencies that prioritize innovation,
      learning, and experimentation. Additionally, more research is required that
      explores the linkages between conservation funding, donor decision-making
      processes, and governance reforms.

PMID- 19765033
TI  - Quantifying habitat requirements of tree-living species in fragmented boreal
      forests with Bayesian methods.
AB  - Quantitative conservation objectives require detailed consideration of the
      habitat requirements of target species. Tree-living bryophytes, lichens, and
      fungi are a critical and declining biodiversity component of boreal forests. To
      understand their requirements, Bayesian methods were used to analyze the
      relationships between the occurrence of individual species and habitat factors at
      the tree and the stand scale in a naturally fragmented boreal forest landscape.
      The importance of unexplained between-stand variation in occurrence of species
      was estimated, and the ability of derived models to predict species' occurrence
      was tested. The occurrence of species was affected by quality of individual
      trees. Furthermore, the relationships between occurrence of species at the tree
      level and size and shape of stands indicated edge effects, implying that some
      species were restricted to interior habitats of large, regular stands. Yet for
      the habitat factors studied, requirements of many species appeared similar.
      Species occurrence also varied between stands; most of the seemingly suitable
      trees in some stands were unoccupied. The models captured most variation in
      species occurrence at tree level. They also successfully accounted for between
      stand variation in species occurrence, thus providing realistic simulations of
      stand-level occupancy of species. Important unexplained between-stand variation
      in species occurrence warns against a simplified view that only local habitat
      factors influence species' occurrence. Apparently, similar stands will host
      populations of different sizes due to historical, spatial, and stochastic
      factors. Thus, habitat suitability cannot be assessed simply by population sizes,
      and stands lacking a species may still provide suitable habitat and merit
      protection.

PMID- 19765034
TI  - Edge-related variation in medicinal and other "useful" wild plants of Bwindi
      Impenetrable National Park, Uganda.
AB  - Harvesting of wild plants for nontimber uses is widespread in the tropics, but
      its impact is usually quantified only for one or a few species at a time. Thus,
      forest managers are never clear about how well their efforts are protecting such
      plants. We quantified abundance and edge-related variation in 91 species of
      useful wild plants commonly harvested by communities around Bwindi Impenetrable
      National Park (BINP), Uganda, to evaluate the effect of their harvest. Forty
      percent of these species were harvested exclusively for medicines, 22% for
      weaving, and 24% for other uses. Fourteen percent were harvested for combinations
      of uses. Plants were surveyed around the entire periphery of the park transects
      that extended out 1 km into the forest interior from the edge. Analyses of edge
      and interior distribution were controlled for effects of topography.
      Individually, nine (10%) species were very rare, occurring in <0.5% of the plots
      searched. Of the remaining 82 species, most (50%) decreased significantly away
      from the park boundary, whereas 4.9% increased and 45.1% showed no pronounced
      edge-related distributions. Rarer species were no more likely to be less abundant
      near the edge than commoner species. These results suggest that most plants used
      for nontimber purposes in BINP are not currently being harvested unsustainably.
      In this respect many of the species of useful wild plants we examined resembled
      animals commonly hunted in tropical forests for bushmeat because they increased
      in abundance in disturbed habitat. Conservation action should initially aim to
      understand what influences distributions of very rare species. Edge-based
      assessments of distributions may be valuable for revealing harvest impact on
      species of useful wild plants commonly harvested by people living around forest
      islands in the tropics.

PMID- 19765035
TI  - Habitat fragmentation and species loss across three interacting trophic levels:
      effects of life-history and food-web traits.
AB  - Not all species are likely to be equally affected by habitat fragmentation; thus,
      we evaluated the effects of size of forest remnants on trophically linked
      communities of plants, leaf-mining insects, and their parasitoids. We explored
      the possibility of differential vulnerability to habitat area reduction in
      relation to species-specific and food-web traits by comparing species-area
      regression slopes. Moreover, we searched for a synergistic effect of these traits
      and of trophic level. We collected mined leaves and recorded plant, leaf miner,
      and parasitoid species interactions in five 100-m2 transects in 19 Chaco Serrano
      woodland remnants in central Argentina. Species were classified into extreme
      categories according to body size, natural abundance, trophic breadth, and
      trophic level. Species-area slopes differed between groups with extreme values of
      natural abundance or trophic specialization. Nevertheless, synergistic effects of
      life-history and food-web traits were only found for trophic level and trophic
      breadth: area-related species loss was highest for specialist parasitoids. It has
      been suggested that species position within interaction webs could determine
      their vulnerability to extinction. Our results provide evidence that food-web
      parameters, such as trophic level and trophic breadth, affect species sensitivity
      to habitat fragmentation.

PMID- 19765036
TI  - Biodiversity conservation, ecosystem functioning, and economic incentives under
      cocoa agroforestry intensification.
AB  - World chocolate demand is expected to more than double by 2050. Decisions about
      how to meet this challenge will have profound effects on tropical rainforests and
      wild species in cocoa-producing countries. Cocoa, "the chocolate tree," is
      traditionally produced under a diverse and dense canopy of shade trees that
      provide habitat for a high diversity of organisms. The current trend to reduce or
      eliminate shade cover raises concerns about the potential loss of biodiversity.
      Nevertheless, few studies have assessed the ecological consequences and economic
      trade-offs under different management options in cocoa plantations. Here we
      describe the relationships between ant ecology (species richness, community
      composition, and abundance) and vegetation structure, ecosystem functions, and
      economic profitability under different land-use management systems in 17
      traditional cocoa forest gardens in southern Cameroon. We calculated an index of
      profitability, based on the net annual income per hectare. We found significant
      differences associated with the different land-use management systems for species
      richness and abundance of ants and species richness and density of trees. Ant
      species richness was significantly higher in floristically and structurally
      diverse, low-intensity, old cocoa systems than in intensive young systems. Ant
      species richness was significantly related to tree species richness and density.
      We found no clear relationship between profitability and biodiversity.
      Nevertheless, we suggest that improving the income and livelihood of smallholder
      cocoa farmers will require economic incentives to discourage further
      intensification and ecologically detrimental loss of shade cover. Certification
      programs for shade-grown cocoa may provide socioeconomic incentives to slow
      intensification.

PMID- 19765037
TI  - Relationships between sensitivity to agricultural intensification and ecological
      traits of insectivorous mammals and arthropods.
AB  - We tested the hypothesis that variation in the sensitivity of animals to habitat
      change is explained by ecological traits (life-history traits, trophic level, and
      mobility). We measured the sensitivity of insectivorous mammals (shrews and bats)
      and their prey (arthropods active at the soil surface and nocturnal aerial
      arthropods) to three aspects of agricultural intensification in a matched-pair
      experimental design: increased use of agrochemicals (comparison of organic and
      conventional cereal crops, with pairing for the size of the boundary hedge),
      change in grassland management from hay to silage (with pairing for the size of
      the boundary hedge), and increased field size due to hedgerow loss (with boundary
      field comparisons as a proxy). We assessed the sensitivity of taxa as the
      difference in their relative abundance between pairs of high- and low-intensity
      sites for each aspect of agricultural intensification. We used phylogenetically
      informed analyses to explore cross-species relationships between our measures of
      sensitivity and seven ecological traits of animals (e.g., trophic level,
      mobility, and reproductive rate). Several traits were related to the sensitivity
      of animals to agricultural intensification. These traits were mainly associated
      with fast life histories (high reproductive output and low trophic level) and low
      mobility. Trophic level of adults was related to sensitivity to habitat change
      for all three aspects of agricultural intensification, but the direction of the
      relationship differed between the three aspects of intensification. The
      significance of the relationship between other ecological traits and sensitivity
      to intensification varied for the three aspects of agricultural intensification.
      Our results show that some ecological traits can be used to preselect taxa that
      are predicted to be sensitive to habitat change, and their sensitivity can be
      tested empirically for use as biotic indicator taxa. Understanding which traits
      are related to sensitivity to habitat change is vital because sensitivity is
      important in determining a taxon's ability to survive in dynamic environments.

PMID- 19765038
TI  - Efficacy of land-cover models in predicting isolation of marbled salamander
      populations in a fragmented landscape.
AB  - Amphibians worldwide are facing rapid declines due to habitat loss and
      fragmentation, disease, and other causes. Where habitat alteration is implicated,
      there is a need for spatially explicit conservation plans. Models built with
      geographic information systems (GIS) are frequently used to inform such planning.
      We explored the potential for using GIS models of functional landscape
      connectivity as a reliable proxy for genetically derived measures of population
      isolation. We used genetic assignment tests to characterize isolation of marbled
      salamander populations and evaluated whether the relative amount of modified
      habitat around breeding ponds was a reliable indicator of population isolation.
      Using a resampling analysis, we determined whether certain land-cover variables
      consistently described population isolation. We randomly drew half the data for
      model building and tested the performance of the best models on the other half
      100 times. Deciduous forest was consistently associated with lower levels of
      population isolation, whereas salamander populations in regions of agriculture
      and anthropogenic development were more isolated. Models that included these
      variables and pond size explained 65-70% of variation in genetically inferred
      isolation across sites. The resampling analysis confirmed that these habitat
      variables were consistently good predictors of isolation. Used judiciously,
      simple GIS models with key land-cover variables can be used to estimate
      population isolation if field sampling and genetic analysis are not possible.

PMID- 19765039
TI  - Hunting for sustainability in tropical secondary forests.
AB  - The interaction between land-use change and the sustainability of hunting is
      poorly understood but is critical for sustaining hunted vertebrate populations
      and a protein supply for the rural poor. We investigated sustainability of
      hunting in an Amazonian landscape mosaic, where a small human population had
      access to large areas of both primary and secondary forest. Harvestable
      production of mammals and birds was calculated from density estimates. We
      compared production with offtake from three villages and used catch-per-unit
      effort as an independent measure of prey abundance. Most species were hunted
      unsustainably in primary forest, leading to local depletion of the largest
      primates and birds. The estimated sustainable supply of wild meat was higher for
      primary (39 kg x km(-2) x yr(-1)) than secondary forest (22 kg x km(-2) x yr(-1))
      because four species were absent and three species at low abundance in secondary
      forests. Production of three disturbance-tolerant mammal species was 3 times
      higher in secondary than in primary forest, but hunting led to overexploitation
      of one species. Our data suggest that an average Amazonian smallholder would
      require > or = 3.1 km2 of secondary regrowth to ensure a sustainable harvest of
      forest vertebrates. We conclude that secondary forests can sustainably provide
      only 2% of the required protein intake of Amazonian smallholders and are unlikely
      to be sufficient for sustainable hunting in other tropical forest regions.

PMID- 19765040
TI  - Protected-area monitoring dilemmas: a new tool to assess success.
AB  - Understanding factors that influence the success of protected areas in curbing
      unsustainable resource consumption is essential for determining best management
      strategies and allocating limited resources to those projects most likely to
      succeed. I used a law-enforcement and monitoring game-theory model from the
      political science literature to identify three key variables useful in predicting
      the success of a protected area: costs of monitoring for rule breakers, benefits
      of catching a rule breaker, and probability of catching a rule breaker if
      monitoring. Although assigning exact values for each of these variables was
      difficult, the variables had a strong predictive capacity even when coded as
      coarse ordinal values. A model in which such values were used correctly predicted
      the outcome of 88 of 116 protected areas sampled from the peer-reviewed
      literature. The model identified a critical zone of common mismatch between
      protected-area circumstances and management policies. In situations where the
      costs of monitoring were greater than the product of the probability of catching
      a rule breaker and the benefit of doing so, conservation was unlikely to succeed.
      Control of illegal use of protected resources was reported in only 8% of such
      cases, regardless of strategies to motivate potential users to cooperate with
      conservation. My model does not prescribe a best management policy for conserving
      natural resources; rather, it can be used as a tool to help predict whether a
      proposed management policy will likely succeed in a given situation.

PMID- 19765041
TI  - A cross-national analysis of how economic inequality predicts biodiversity loss.
AB  - We used socioeconomic models that included economic inequality to predict
      biodiversity loss, measured as the proportion of threatened plant and vertebrate
      species, across 50 countries. Our main goal was to evaluate whether economic
      inequality, measured as the Gini index of income distribution, improved the
      explanatory power of our statistical models. We compared four models that
      included the following: only population density, economic footprint (i.e., the
      size of the economy relative to the country area), economic footprint and income
      inequality (Gini index), and an index of environmental governance. We also tested
      the environmental Kuznets curve hypothesis, but it was not supported by the data.
      Statistical comparisons of the models revealed that the model including both
      economic footprint and inequality was the best predictor of threatened species.
      It significantly outperformed population density alone and the environmental
      governance model according to the Akaike information criterion. Inequality was a
      significant predictor of biodiversity loss and significantly improved the fit of
      our models. These results confirm that socioeconomic inequality is an important
      factor to consider when predicting rates of anthropogenic biodiversity loss.

PMID- 19765042
TI  - Ecological silence of the grasslands, forests, wetlands, mountains, and seas.

PMID- 19765050
TI  - Effects of pioglitazone and rosiglitazone combined with metformin on body weight
      in people with diabetes.
AB  - Currently, pioglitazone and rosiglitazone are the thiazolidinediones available
      for clinical use. In the literature, there are different studies concerning the
      efficacy, safety and tolerability of thiazolidinediones as add-on therapy to
      metformin in patients with type 2 diabetes inadequately controlled with metformin
      alone. Metformin and thiazolidinediones are both antihyperglycaemic drugs, both
      lower blood glucose concentrations in type 2 diabetes without causing overt
      hypoglycaemia and both require the presence of insulin to generate their
      therapeutic effects, but act without stimulating insulin secretion. Some authors
      reported that the improved glycaemic control obtained with thiazolidinediones is
      associated with an increase in body weight with an estimated 2-3 kg weight gain
      for every 1% decrease in HbA(1c) which could negate some of the benefits of the
      improved metabolic control. Some other authors, instead, reported that
      thiazolidinediones give a better improvement in the glycaemic control compared
      with metformin alone without giving weight gain. The emerging discrepancies from
      these studies could be because of the study design, the patient selection, the
      degree of glycaemic control and/or the methods to measure body weight. We have
      undertaken a thorough literature search on Medline and Embase to evaluate the
      effects of thiazolidinediones plus metformin combination in people with diabetes
      on the body weight.

PMID- 19765051
TI  - Lower limb involvement in adult-onset primary dystonia: frequency and clinical
      features.
AB  - BACKGROUND AND PURPOSE: Despite the growing number of reports describing adult
      onset primary lower limb dystonia (LLD) this entity has never been systematically
      evaluated in the general population of patients with primary adult-onset
      dystonia. METHODS: From outpatients with adult-onset primary dystonia attending
      nine Italian University centres for movement disorders we consecutively recruited
      579 patients to undergo a standardized clinical evaluation. RESULTS: Of the 579
      patients assessed, 11 (1.9%) (8 women, 3 men) had LLD, either alone (n = 4, 0.7%)
      or as part of a segmental/multifocal dystonia (n = 7, 1.2%). The age at onset of
      LLD (47.9 +/- 17 years) was significantly lower than the age at onset of cranial
      dystonias (57.9 +/- 10.7 years for blepharospasm, and 58.9 +/- 11.8 years for
      oromandibular dystonia) but similar to that of all the other adult-onset primary
      dystonias. The lower limb was either the site of dystonia onset (36.4%) or the
      site of dystonia spread (63.6%). In patients in whom LLD was a site of spread,
      dystonia seemed to spread following a somatotopic distribution. Only one patient
      reported a recent trauma involving the lower limb whereas 36.4% of the patients
      reported pain at the site of LLD. Only 64% of our patients needed treatment for
      LLD, and similarly to previously reported cases, the most frequently tried
      treatments was botulinum toxin and trihexyphenidyl. CONCLUSION: The lower limb is
      an uncommon but possible topographical site of dystonia in adulthood that should
      be kept in consideration during clinical evaluation.

PMID- 19765052
TI  - Birds and penguins in the brainstem of progressive supranuclear palsy
      patients...and not.

PMID- 19765053
TI  - To gamble or not to gamble: is that a decision?

PMID- 19765054
TI  - Angioplasty and stenting of symptomatic and asymptomatic vertebral artery
      stenosis: to treat or not to treat.
AB  - BACKGROUND AND PURPOSE: Comprehensive indications for treatment of symptomatic
      vertebral stenosis remain unavailable. Even less is known about endovascular
      treatment of asymptomatic cases. We treated symptomatic and asymptomatic
      vertebral ostium stenosis with angioplasty and stenting and investigated the long
      term outcome. METHODS: Consecutive patients with two different indications were
      included. Group 1 (G1) had symptomatic >50% stenosis. Group 2 (G2) had
      asymptomatic >50% stenosis and severe lesions of anterior circulation and were
      expected to benefit from additional cerebral blood supply. RESULTS: Twenty nine
      vertebral origin stenoses in 28 patients (75% men, mean age 64 +/- 9 years) were
      treated. There were 16 G1 and 13 G2 cases. Technical success rate was 100%.
      Immediate neurological complications rate was 3.4% (one G1 patient with vertebral
      TIA due to release of emboli). Two further strokes were seen during follow up (32
      +/- 24 months): vertebrobasilar stroke in a G2 patient with permeable stent in V1
      segment, new ipsilateral V3 occlusion and high-risk cardioembolic source, and
      carotid stroke in a G1 patient who had had ipsilateral carotid stenting. There
      were no deaths of any cause. Asymptomatic restenosis was observed in one out of
      19 patients from both groups who underwent a follow up angiography. CONCLUSIONS:
      Angioplasty and stenting appears to be technically feasible and safe in
      asymptomatic and symptomatic vertebral stenosis. More studies are needed in order
      to clarify its role in primary and secondary prevention of vertebrobasilar
      stroke. High risk anterior circulation lesions should be taken into account as a
      possible indication in patients with asymptomatic vertebral stenosis.

PMID- 19765055
TI  - Impairment of rapid repetitive finger movements and visual reaction time in
      patients with essential tremor.
AB  - BACKGROUND AND PURPOSE: The question whether patients with essential tremor (ET)
      have slowed movements as part of their clinical manifestations is still a matter
      of controversy. We analyzed basic motor function in patients with ET and in
      healthy matched controls. METHODS: We studied 61 patients with ET and 122 age-
      and sex-matched controls. Evaluation included four timed tests (pronation
      supination, finger tapping and movement between two points, all with both hands,
      and walking test); and three tests performed on a personal computer (speed for
      pressing repetitively a key - frequency, visual reaction time and movement time,
      all with both hands). RESULTS: Essential tremor patients showed higher mean
      values for right and left finger tapping, left movement between two points; and
      with right and left frequency and reaction time. In the logistic regression
      study, ET patients showed significantly higher values than controls for right and
      left finger tapping; mean, SD, maximum and rank values of right and left
      frequency; and mean, SD, minimum, maximum and rank values of right and left
      visual reaction time. Tremor severity was not correlated with the altered values.
      CONCLUSIONS: Patients with ET showed impaired motor performance, at least in some
      tasks, such as rapid repetitive finger movements (finger tapping and frequency)
      and visual reaction time (impairment was not related with tremor severity). This
      probably means that patients with ET have some degree of bradykinesia.

PMID- 19765056
TI  - Publishing affects funding in neurology.
AB  - BACKGROUND AND PURPOSE: A new national system for funding research in
      universities and hospitals in Norway based on publication output is described.
      METHODS: All scientific publications were counted and weighted according to the
      quality of the publication channel. Author addresses were credited. This led to a
      number of publication points for each institution/department. RESULTS: The number
      of publication points for neurology had increased from 75.0 in 2005 to 98.3 in
      2007. Publishing and the quality of publications were given more attention than
      before, and there was a stronger focus on facilitating research at the
      institutions. Research was regarded as not only an institutional but also as an
      individual responsibility. CONCLUSIONS: The principle of performance-based
      funding in addition to funding based on project applications has been well
      received, and it stimulates more and better research. Scientific publications
      represent a useful marker, whereas the way of counting author addresses and
      determining quality is still debated.

PMID- 19765057
TI  - Large scale study of epidermal recovery after stratum corneum removal: dynamics
      of genomic response.
AB  - The stratum corneum (SC) is a superficial skin compartment that protects the body
      from the outside environment. Any disturbance of this function induces cascading
      steps of molecular and cellular repair in the whole epidermis. The aim of this
      study was to investigate epidermal gene expression following SC removal by tape
      stripping. Twenty-nine healthy male volunteers were included (27 +/- 4 years
      old). Tape stripping was processed on one inner forearm, the other unstripped
      forearm served as a control. Epidermis samples were collected at 2, 6, 19, 30 and
      72 h after tape stripping. Trans-epidermal water loss measurements were performed
      at each step to monitor barrier restoration. Total RNA was extracted from
      collected epidermis samples and analysed by using DermArray cDNA microarrays.
      Among 4000 genes under investigation, we found that the expression of 370 genes
      varied significantly at least once during the time following stripping. Using an
      original clustering method, the modulated genes were gathered into eight groups.
      A functional characterization of the clusters enabled us to get a dynamic and
      global view of the main molecular processes taking place during epidermal
      recovery.

PMID- 19765058
TI  - Hirseins inhibit melanogenesis by regulating the gene expressions of Mitf and
      melanogenesis enzymes.
AB  - Previously, we reported that Thymelaea hirsuta extract has antimelanogenesis
      effect on B16 murine melanoma cells. The extract was subjected to fractionation,
      and hirsein A (HA) and hirsein B (HB) were discovered and tested for their
      ability to regulate melanogenesis in B16 cells. Western blot (WB) analysis was
      carried out to determine the expression of tyrosinase. Moreover, to elucidate the
      possible mechanism behind melanogenesis regulation, real-time PCR using primers
      for Mitf, Tyr, Trp1 and Dct genes, and protein kinase C (PKC) activity assay were
      carried out. Results clearly show that 0.1 mum HA and HB significantly reduced
      the melanin content. This reduction in melanin content was accompanied by reduced
      tyrosinase expression as detected by WB analysis. There was also a significant
      decrease in the expression level of Mitf gene in HA- and HB-treated cells. HA
      down-regulated the expressions of Tyr, Trp1 and Dct, whereas HB down-regulated
      only those of Trp1 and Dct. Interestingly, HB-treated cells had lower kinase
      activity than HA-treated cells indicating a possible difference in the activities
      of the compounds but with the same mechanism of melanogenesis regulation. We
      report for the first time that HA and HB can down-regulate melanogenesis by down
      regulating Mitf gene expression, leading to reduced expressions of Tyr, Trp1 and
      Dct. The hirseins were also able to reduce the kinase activity, suggesting the
      possible involvement of PKC in the overall ability of the hirseins to down
      regulate melanogenesis.

PMID- 19765059
TI  - Left ventricular untwisting in restrictive and pseudorestrictive left ventricular
      filling: novel insights into diastology.
AB  - BACKGROUND: Conceptually, an ideal therapeutic agent should target the underlying
      mechanisms that cause left ventricular (LV) diastolic dysfunction. The objective
      of our study was to gain further insight into the mechanics of diastology by
      comparison of LV untwisting measured by speckle tracking echocardiography (STE)
      in young healthy adults with normal and "pseudorestrictive" LV filling, and
      dilated cardiomyopathy (DCM) patients with "true restrictive" LV filling.
      METHODS: The study comprised 20 healthy volunteers with a Doppler LV-inflow
      pattern compatible with restrictive LV filling but a diastolic early phase
      filling velocity/early diastolic velocity of the mitral annulus (E/Em) ratio <8
      ("pseudorestrictive"), 20 for age and gender-matched healthy volunteers with
      normal LV filling and an E/Em ratio <8, and 10 DCM patients with "true
      restrictive" LV filling and an E/Em ratio >15. LV untwisting parameters were
      determined by STE. RESULTS: Compared to healthy subjects, DCM patients had
      decreased peak diastolic untwisting velocity (-62 +/- 33 degrees/s vs -113 +/- 25
      degrees/s, P < 0.01) and untwisting rate (-15 +/- 9 degrees/s vs -51 +/- 24
      degrees/s, P < 0.01). Compared to healthy subjects with normal LV filling,
      healthy subjects with "pseudorestrictive" LV filling had increased peak diastolic
      untwisting velocity (-123 +/- 25 degrees/s vs -104 +/- 30 degrees/s, P < 0.05)
      and untwisting rate (-59 +/- 23 degrees/s vs -44 +/- 22 degrees/s, P < 0.05).
      CONCLUSION: Faster LV untwisting plays a pivotal role in the rapid early
      diastolic filling occasionally seen in young healthy individuals. In contrast, in
      DCM patients untwisting is severely delayed and this impairment to utilize
      suction may reduce LV filling.

PMID- 19765060
TI  - Ventricular mechanical asynchrony in patients with different degrees of systolic
      dysfunction: results from AVE Registry by the Italian Society of Cardiovascular
      Echography (SIEC).
AB  - OBJECTIVE: The aim of the study was to compare the prevalence of interventricular
      and intraventricular asynchrony in patients with different degrees of left
      ventricular (LV) dysfunction. METHODS: We enrolled 182 patients (male 79%, mean
      age 64 +/- 11 years) with LV ejection fraction (EF) < 50% and identified two
      groups: Group A (n = 79) with mild-to-moderate LV dysfunction (EF between 36% and
      49%) and Group B (n = 103) with severe dysfunction (EF <or= 35%). An
      echocardiogram was performed in all patients and a delay longer than 40 msec in
      the time difference between the aortic and pulmonary preejection intervals was
      considered as an index of interventricular asynchrony. The electromechanical
      delays were assessed by pulsed tissue Doppler technique. A time difference
      between the earliest and the latest segment greater than 40 msec was considered
      the cutoff for intraventricular asynchrony. The sum of asynchrony was calculated
      by adding to the LV intraventricular delay the delay between the lateral basal
      right ventricular segment and the most delayed LV basal segment. RESULTS: The
      prevalence of interventricular asynchrony was lower among Group A patients (19.8%
      vs. 37.9%; P = 0.007) while the prevalence of intraventricular asynchrony did not
      differ between groups (32.9% vs. 44% in Group A and Group B respectively; P =
      0.18). The sum of asynchrony (cutoff >102 msec) did not differ between groups
      either (29.9% vs. 35.9%; P = 0.39). CONCLUSIONS: The prevalence of
      intraventricular asynchrony is independent of the LV systolic dysfunction
      severity. This could indicate the potential role of cardiac resynchronization
      therapy in patients with mild-moderate systolic dysfunction.

PMID- 19765061
TI  - Segmental contribution to left ventricular systolic function at rest and stress:
      a quantitative real time three-dimensional echocardiographic study.
AB  - OBJECTIVE: To assess the relative contribution of each myocardial segment to
      global systolic function during stress using real time three-dimensional
      echocardiography (RT3DE). BACKGROUND: During stress, global augmentation in
      contractility results in an increased stroke volume. The relative contribution of
      each myocardial segment to these volumetric changes is unknown. METHODS: Full
      volume was acquired using RT3DE at rest and following peak exercise in 22
      patients who had no ischemia and no systolic dyssynchrony on two-dimensional (2D)
      stress echocardiography. The following were calculated at rest and peak stress:
      end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV),
      ejection fraction (EF), relative SV, and relative EF. RESULTS: With stress, an
      increase in global EDV from 90.8 to 101.1 ml (P < 0.001), SV from 59 to 78.4 ml
      (P = 0.01), and EF from 65.6 to 78.4% (P = 0.001) was observed. ESV decreased
      from 31.8 to 22.7 ml (P < 0.001). Segmental analysis revealed significantly
      higher SV, relative SV, and relative EF for the basal anterior, basal
      anterolateral, and basal inferolateral segments compared with the apical septum
      and apical inferior segments at both rest and stress (P < 0.001). The SV,
      relative SV, and relative EF increased significantly from apex to mid to base at
      both rest and stress (P < 0.001). CONCLUSIONS: The relative volumetric
      contribution of each myocardial segment to global left ventricular systolic
      function at rest and stress is not uniform. The basal segments contribute more
      than the mid and apical segments. Specifically, the basal anterior, basal
      anterolateral, and basal inferolateral segments contribute the most to
      augmentation of left ventricular systolic function with exercise.

PMID- 19765062
TI  - Left atrial appendage aneurysm secondary to eccentric severe ischemic mitral
      regurgitation.
AB  - Dilatation primarily confined to the left atrial appendage (LAA) is an unusual
      condition in nonrheumatic mitral valve disease. We report a case of 56-year-old
      male with a giant LAA secondary to ischemic severe mitral regurgitation without
      significant dilatation of the left atrial main chamber. The mitral regurgitation
      jet was directed toward the LAA, which we thought as the cause of
      disproportionate LAA enlargement.

PMID- 19765063
TI  - Noninvasive assessment of atherosclerosis in patients with isolated hypertension.
AB  - BACKGROUND: Endothelial dysfunction is considered the first stage in the
      development of atherosclerosis. Brachial artery flow-mediated dilatation (FMD)
      has been used to assess endothelial dysfunction. An impaired FMD response may
      reflect a vascular phenotype prone to atherosclerosis. The thickness of the
      common carotid intima-media (CIMT) as measured by ultrasound represents a marker
      of structural atherosclerosis. Recently, it has been shown that color M-mode
      propagation velocity measured along the origin of descending thoracic aorta (AVP)
      may reflect atherosclerosis. In this study, the effects of isolated hypertension
      on these atherosclerosis markers are investigated. METHODS: Fifty patients with
      newly diagnosed hypertension and forty healthy people were enrolled. Patients
      were evaluated with transthoracic echocardiography. Diastolic functions were
      evaluated by transmitral filling parameters of deceleration time (DT), E/A ratio,
      and isovolumetric relaxation time (IVRT). Carotid intima-media thickness, FMD,
      and AVP were measured. RESULTS: Age, gender, and BMI of both groups were similar.
      Compared to control group CIMT, DT and IVRT values were significantly higher, and
      FMD and AVP values were significantly lower in hypertensive patients. There were
      significant correlations between AVP and CIMT (r =-0.699, P < 0.001), AVP and FMD
      (r = 0.400, P < 0.001), and FMD and CIMT (r =-0.600, P < 0.001). Carotid intima
      media thickness, AVP, and FMD were significantly correlated with systolic and
      diastolic blood pressures and DT and IVRT. CONCLUSIONS: In patients with isolated
      hypertension, AVP and FMD decrease and CIMT increases. In addition, CIMT is
      inversely correlated with AVP and FMD, and AVP is directly correlated with FMD.

PMID- 19765064
TI  - Measurement of the myocardial performance index in ambulatory patients with heart
      failure: correlation with other clinical and echocardiographic parameters and
      independent prognostic value.
AB  - BACKGROUND: Many echocardiographic parameters have been proposed for the
      assessment of the patients with heart failure (HF). Recently, the myocardial
      performance index (MPI) has been shown to be an accurate index of myocardial
      function. We assessed the correlation with other clinical and echocardiographic
      measurements and the prognostic value of MPI in patients with HF. METHODS AND
      RESULTS: The MPI was assessed in 112 consecutive patients with persistent
      symptoms of HF (II-III NYHA class), sinus rhythm, LV systolic dysfunction
      (defined by an ejection fraction <or= 45%). At multivariable analysis, only NYHA
      class and ejection fraction were independently related to MPI. The severity of
      mitral regurgitation and MPI were the only parameters independently related to
      the incidence of death or cardiovascular hospitalizations. A MPI > 0.55 (median
      value) and medium to severe mitral regurgitation were associated with a relative
      risk of cardiovascular events of 18.7 (95% confidence interval [CI], 16.6-20.7; P
      < 0.005) and of 3.03 (95% CI, 2-4.1; P = 0.035), respectively. CONCLUSIONS: In
      our patients with HF, MPI was the best predictor of cardiovascular events. Mitral
      regurgitation was the only other variable which had an additive prognostic value
      at multivariate analysis.

PMID- 19765065
TI  - Persistent ventricular asynchrony after coronary artery bypass surgery predicts
      cardiac events.
AB  - AIM: The aim of this study was to identify echocardiographic LV systolic and
      diastolic measurements that predict clinical events post-coronary artery bypass
      graft (CABG) surgery. METHODS: We collected data from 27 patients (age 70 +/- 7
      years) who underwent elective CABG, before and within 6 weeks after surgery. LV
      systolic function was assessed by conventional echocardiographic parameters. A
      number of LV filling measurements were also made, which included total isovolumic
      time (t-IVT), Tei index, and restrictive filling pattern. Postoperative cardiac
      events were death or hospitalization for chest pain, breathlessness, or
      arrhythmia. RESULTS: Patient's follow-up period was 17 +/- 10 months. Of the 27
      patients (age 70 +/- 7 years, 22 male), 10 had postoperative cardiac events. LV
      ejection fraction (EF) and fractional shortening (FS) were lower (P = 0.01, and P
      = 0.007, respectively), t-IVT longer (P < 0.001), and Tei index was higher (P <
      0.001) preoperatively in patients with events compared to those without. The same
      differences between groups remained after surgery; EF (P = 0.002), FS (P =
      0.002), t-IVT (P < 0.001), and Tei index (P < 0.001). T-IVT was the only
      preoperative predictor of events (P = 0.038) but its postoperative value as well
      as that of FS predicted events (P = 0.034, and P = 0.042, respectively). T-IVT of
      12.2 s/min and FS of 26% were 80% sensitive and 88% specific for predicting
      postoperative events. CONCLUSION: Despite successful surgical revascularization
      residual impairment of LV systolic function and persistent asynchrony in the form
      of prolonged t-IVT are associated with postoperative events. Since these
      abnormalities remained despite full medical therapy, they may thus suggest a need
      for electrical resynchronization therapy.

PMID- 19765066
TI  - Ten-year echo/doppler determination of the benefits of aerobic exercise after the
      age of 65 years.
AB  - As the human lifespan becomes progressively extended, potential health-related
      effects of intense aerobic exercise after age 65 need evaluation. This study
      evaluates the cardiovascular (CV), pulmonary, and metabolic effects of
      competitive distance running on age-related deterioration in men between 69 (+/
      3) and 77 (+/-2) years (mean +/- SD). Twelve elderly competitive distance runners
      (ER) underwent oxygen consumption and echo/Doppler treadmill stress testing
      (Balke protocol) for up to 10 years. Twelve age-matched sedentary controls (SC)
      with no history of CV disease were similarly tested and the results compared for
      the initial three series of the study. CV data clearly separated the ER from SC.
      At entry, resting and maximal heart rate, systolic/diastolic blood pressure, peak
      oxygen consumption (VO(2max)), and E/A ratio of mitral inflow were better in the
      ER (P < 0.05 vs. SC). With aging, ER had a less deterioration of multiple health
      parameters. Exceptions were VO(2max) and left ventricular diastolic function
      (E/A, AFF, IVRT) that decreased (P < 0.05, Year 10 vs. Year 1). Health advantages
      of high-level aerobic exercise were demonstrated in the ER when compared to SC.
      Importantly, data collected in ER over 10 years confirm the benefit of intensive
      exercise for slowing several negative effects of aging. However, the normative
      drop of exercise capacity in the seventh and eighth decades reduces the potential
      athleticism plays in prevention of CV events.

PMID- 19765067
TI  - Adult-type anomalous origin of the left coronary artery from the main pulmonary
      artery: one case report.
AB  - Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA)
      is a rare congenital defect that presents even less frequently in adults. Here we
      described a 40-year-old patient presenting with palpitations. Electrocardiography
      revealed frequent ventricular ectopy. Echocardiography revealed a dilated left
      ventricle and an abnormal flow pattern in the pulmonary artery and at the right
      side of the interventricular septum. Coronary angiography demonstrated an
      enlarged right coronary artery (RCA) with collateralization to the left coronary
      artery (LCA) and reflux of contrast into the pulmonary artery. Computed
      tomography confirmed ALCAPA syndrome. Surgical corrections were planned.

PMID- 19765068
TI  - Measurement of left ventricular ejection fraction by real time 3D
      echocardiography in patients with severe systolic dysfunction: comparison with
      radionuclide angiography.
AB  - AIM: Measurement of left ventricular ejection fraction (LVEF) using real time 3D
      echocardiography (3DE) has been performed in subjects with preserved or modestly
      reduced systolic function. Our aim was to evaluate this technique in the subset
      of patients with severe systolic dysfunction. METHODS AND RESULTS: Consecutive
      patients with LVEF less than 0.35 at two-dimensional echocardiography were
      included. LVEF obtained by 3DE was compared to the value measured by radionuclide
      angiography (RNA). Real time full-volume 3DE was performed, with offline
      semiautomated measurement of LVEF using dedicated software (Cardioview RT,
      Tomtec) by a single observer blinded to the results of RNA. A total of 50
      patients were evaluated, of whom 38 (76%, 27 males, age 69 +/- 13 years) had a
      3DE of sufficient quality for analysis. LVEF for this group was 0.21 +/- 0.07
      using 3DE and 0.27 +/- 0.08 using RNA. The agreement between the two techniques
      was rather poor (r = 0.49; P < 0.001; 95% limits of agreements of -0.20 to 0.09).
      Truncation of the apex was observed in 6 of 38 (16%) patients. CONCLUSION: In
      patients with severe systolic dysfunction, 3DE shows poor agreement for
      measurement of LVEF as compared to RNA. There may be underestimation of up to 20%
      in absolute terms by 3DE. Accordingly, the two methods are not interchangeable
      for the follow-up of LV function. A limitation of 3DE may, at least in part, be
      related to the incomplete incorporation of the apical region into the pyramidal
      image sector in patients with dilated hearts.

PMID- 19765069
TI  - Three-dimensional echocardiography for quantitative analysis of left-ventricular
      aneurysm.
AB  - BACKGROUND: Quantitative analysis of left-ventricular (LV) aneurysms after
      myocardial infarction is prognostically relevant and assists in planning surgery.
      Three-dimensional (3D) echocardiography facilitates clear visualization of
      cardiac anatomy and accurate assessment of functional parameters. The aim of the
      present study was to determine the ability of 3D echocardiography to quantify LV
      aneurysms. METHODS: Ten patients with a known LV-aneurysm after myocardial
      infarction underwent 3D echocardiography and cardiac magnetic resonance (CMR)
      imaging at 1.5 Tesla within 3 days. For 3D echocardiography, a multiplanar
      transesophageal examination was performed with full LV coverage and the 3D
      dataset was analyzed offline. The LV-aneurysm was defined by a wall thickness <5
      mm. The following quantitative parameters were determined: left ventricular end
      diastolic and end-systolic volumes, LV myocardial mass (LV-mass) and mass of the
      LV-aneurysm. LV ejection fraction and percentage of aneurysm mass (%-aneurysm)
      were calculated. RESULTS: LV volumes and ejection fraction showed a strong
      correlation between 3D echocardiography and CMR (r = 0.94-0.97; P < 0.01).
      Importantly, the mass and percentage of mass of the LV-aneurysm demonstrated a
      high correlation as well (r = 0.94 and r = 0.86, respectively; P < 0.01). For all
      parameters, the calculated bias between both methods was found to be minimal (0.8
      7.6%). CONCLUSIONS: Three-dimensional echocardiography proved to be a reliable
      tool for quantitative analysis of LV volumes, ejection fraction and aneurysm size
      in patients with prior myocardial infarction. In addition, 3D visualization of
      the complex cardiac anatomy in patients with LV-aneurysm may assist surgical
      procedure planning.

PMID- 19765070
TI  - Study of left ventricular rotation and torsion in the acute phase of ST-elevation
      myocardial infarction by speckle tracking echocardiography.
AB  - BACKGROUND: The mechanics of the complex left ventricular (LV) myocardial fiber
      architecture may accurately be assessed by speckle tracking echocardiography
      (STE). The role of STE to assess LV mechanical dysfunction in the setting of ST
      segment elevation myocardial infarction (AMI) is still poorly studied. PATIENTS
      AND METHODS: 29 consecutive patients (55 +/- 13 years) presenting with AMI
      underwent STE within 72 hours of admission. Reperfusion was achieved with
      thrombolysis in 15 patients and with primary percutaneous coronary intervention
      in 14. LV rotational and torsion data were registered during peak systole.
      Standard Doppler data included LV ejection fraction (EF), mitral inflow
      deceleration time (DT), and conventional E/A ratio. E/E' ratio (mitral inflow E
      velocity/tissue Doppler E velocity) was calculated as a marker of LV filling
      pressure. Twelve subjects with clinically indicated but negative dobutamine
      stress echocardiogram served as Controls. RESULTS: Peak systolic torsion was not
      only significantly lower in AMI compared with Controls (13.3 +/- 7.6 vs. 21.8 +/-
      6.1; P < 0.01), it was also lower in subjects with LVEF <40% (5.0 +/- 2.9)
      compared with those who had LVEF >40% (10.6 +/- 6.6; P < 0.02). Torsion had a
      modest but significantly positive linear relation (R = 0.6; P < 0.05) with DT,
      not with E/E' or LVEF. CONCLUSION: LV systolic torsion is decreased in AMI and
      more markedly decreased in patients with LVEF <40%. The most significant linear
      relationship between DT and torsion may possibly indicate that the LV mechanical
      dysfunction is also associated with altered filling dynamics.

PMID- 19765071
TI  - Cardiac structural and functional changes in competitive amateur cyclists.
AB  - PURPOSE: To assess cardiac structural and functional changes induced by
      competitive amateur cycling. METHODS: Fifty-one young competitive amateur male
      cyclists and 47 age- and gender-matched control subjects underwent complex
      transthoracic echocardiographic examination focused on the detailed assessment of
      cardiac size and function, especially of the left ventricle (LV). Subsequently,
      spiroergometry was performed in all study participants and its results were
      compared to echocardiographic data. RESULTS: Higher left ventricular mass indexes
      due to the greater LV wall thickness and LV end-diastolic diameter were found in
      amateur cyclists as compared to control subjects. There were no differences with
      regard to the LV systolic function parameters. However, significantly better
      indices of LV diastolic function were present in cyclists. A significant
      correlation between maximal oxygen pulse and LV mass index/height(2.7), LV
      diastolic parameters and right ventricular size was noted. CONCLUSIONS: Amateur
      competitive cycling leads to considerable LV structural and functional changes.
      The increases in LV wall thickness and cavity size together with supranormal
      diastolic properties are key characteristics of this LV remodeling. As well, LV
      mass, diastolic function, and RV size are predictors of exercise capacity,
      indicating an important involvement of these elements in improving cardiac
      function with endurance training.

PMID- 19765072
TI  - Right atrial metastasis mimicking myxoma in advanced hepatocellular carcinoma.
AB  - Hepatocellular carcinoma is the most common primary tumor of the liver accounting
      for 4.6% of all new human cancers. Cardiac metastasis in hepatocellular carcinoma
      is an uncommon secondary cardiac malignancy. We described two cases of advanced
      hepatocellular carcinoma with large masses in the right atrium mimicking atrial
      myxoma. The RA masses were incidentally detected during two-dimensional
      echocardiographic examination.

PMID- 19765073
TI  - Association of left atrial strain and strain rate assessed by speckle tracking
      echocardiography with paroxysmal atrial fibrillation.
AB  - BACKGROUND: We hypothesized that contraction of the LA wall could be documented
      by speckle tracking and could be applied for assessment of LA function. This
      study tried to identify the association between LA longitudinal strain (LAS) and
      strain rate (LASR) measured by speckle tracking with paroxysmal atrial
      fibrillation (PAF). METHODS: Fifty-two patients (61 +/- 17 years old, 23 men)
      with sinus rhythm at baseline referred for the evaluation of episodic palpitation
      were included. Standard four-chamber and two-chamber views were acquired and
      analyzed off-line. Peak LAS and LASR were carefully identified as the peak
      negative inflection of speckle tracking waves after P-wave gated by
      electrocardiography. RESULTS: Ten patients (19%) had PAF. LAS, LASR, age, left
      ventricular end-diastolic dimension, left ventricular mass, LA volume, and mitral
      early filling-to-annulus early velocity ratio were different between patients
      with and without PAF. After multivariate analysis, LASR was significantly
      independently associated with PAF (OR 8.56, 95% CI 1.14-64.02, P = 0.036).
      CONCLUSION: Speckle tracking echocardiography could be used in measurements of
      LAS and LASR. Decreased negative LASR was independently associated with PAF.

PMID- 19765074
TI  - Altered early left ventricular diastolic wall velocities in pulmonary
      hypertension: a tissue Doppler study.
AB  - BACKGROUND: Left ventricular diastolic dysfunction (LVDD) is known to occur in
      severe chronic pulmonary hypertension (PH); however, the mechanism(s) remains
      unclear. METHODS: Tissue Doppler imaging (TDI) was used to track early (E)
      diastolic signals of basal and mid portions of the interventricular septum (IS)
      and LV free wall (LVFw) in 20 patients (60 +/- 8 years) with documented LVDD
      without PH and in 30 patients (60 +/- 11 years) with known chronic PH. All
      subjects were in normal sinus rhythm and had normal LV ejection fraction.
      RESULTS: PH patients had lower early (E) wave velocities in basal IS (-4.2 +/-
      1.9 vs. -5.9 +/- 1.2 cm/sec; P < 0.001), distal IS (-2.6 +/- 2.6 vs. -4.2 +/- 1.1
      cm/sec; P < 0.01), and basal LVFw (-5.2 +/- 1.7 vs. -6.5 +/- 1.2 cm/sec; P <
      0.01) than patients with LVDD and no PH. Finally, worsening PH distorts the
      entire IS diastolic tracing resulting in asynchronous diastolic signals.
      CONCLUSIONS: The presence of PH not only decreases IS early (E) wave diastolic
      velocity generation but also distorts the entire pattern of IS diastolic
      relaxation when compared to patients with typical LVDD and no PH. Further studies
      are now needed to assess the full effect of PH on LV diastole and how this
      influences clinical outcomes.

PMID- 19765075
TI  - Two-dimensional ultrasound speckle tracking imaging in evaluation of early
      changes in left ventricular diastolic function in patients with essential
      hypertension.
AB  - OBJECTIVE: To investigate two-dimensional ultrasound speckle tracking imaging
      (STI) in evaluating values of early changes in left ventricular diastolic
      function in patients with essential hypertension (EH). METHODS: Seventy-five EH
      patients with left ventricular normal geometry (LVN), including 38 cases with
      nonleft atrial enlargement (NLAE) and 37 cases with left atrial enlargement
      (LAE), and 50 healthy persons were enrolled as study participants. Two
      dimensional images of LV apical four-chamber view, two chamber view, and LV long
      axis view and short-axis view of mitral annular, papillary muscle, and apical
      levels were obtained to measure early diastolic E' peak value, late diastolic A'
      peak value, and E'/A' ratio at LV apical longitudinal strain rate (SrL) and short
      axis radial strain rate (SrR), circumferential strain rate (SrC), and rotation
      rate (RotR) in all cardiac segments. Average values of E', A', and E'/A' at SrL
      in three segments on long-axis and SrR, SrC, and RotR on three short-axis levels
      were calculated. Untwisting rate (Untw R) and untwisting half-time (UHT) were
      also calculated. RESULTS: (1) Data on 110 of 125 patients were usable for STI
      analysis. (2) There were no intersegment significant differences between A' at
      SrL in three segments or interlevel significant differences between A' at SrR in
      three levels in the NLAE group and the LAE group. (3) Compared with the normal
      group, E' at SrL and E'/A' at SrL, SrR and SrC, and Untw R reduced in the NLAE
      group and the LAE group, while A' at SrL, SrR, and SrC and E' at RotR increased
      and UHT extended. CONCLUSION: STI may be helpful for the detection of early
      changes in left ventricular diastolic function in patients with EH.

PMID- 19765076
TI  - Identification of the amniotic fluid insulin-like growth factor binding protein-1
      phosphorylation sites and propensity to proteolysis of the isoforms.
AB  - Insulin-like growth factor binding protein-1 (IGFBP-1) is the major secreted
      protein of human decidual cells during gestation and, as a modulator of insulin
      like growth factors or by independent mechanisms, regulates embryonic
      implantation and growth. The protein is phosphorylated and this post
      translational modification is regulated in pregnancy and represents an important
      determinant of its biological activity. We have isolated, from human normal
      amniotic fluid collected in the weeks 16-18, the intact nonphosphorylated IGFBP-1
      and five electrophoretically distinct phosphoisoforms and have determined their
      in vivo phosphorylation state. The unmodified protein was the most abundant
      component and mono-, bi-, tri- and tetraphosphorylated forms were present in
      decreasing amounts. The phosphorylation sites of IGFBP-1 were identified by
      liquid chromatography-tandem mass spectrometry analysis of the peptides generated
      with trypsin, chymotrypsin and Staphylococcus aureus V8 protease. Five serines
      were found to be phosphorylated and, of these, four are localized in the central,
      weakly conserved, region, at positions 95, 98, 101 and 119, whereas one, Ser169,
      is in the C-terminal domain. The post-translational modification predominantly
      involves the hydrophilic stretch of amino acids representing a potential PEST
      sequence (proline, glutamic acid, serine, threonine) and our results show that
      the phosphorylation state influences the propensity of IGFBP-1 to proteolysis.

PMID- 19765077
TI  - Relationship between functional activity and protein stability in the presence of
      all classes of stabilizing osmolytes.
AB  - We report the effects of stabilizing osmolytes (low molecular mass organic
      compounds that raise the midpoint of thermal denaturation) on the stability and
      function of RNase-A under physiological conditions (pH 6.0 and 25 degrees C).
      Measurements of Gibbs free energy change at 25 degrees C (DeltaG(D) degrees ) and
      kinetic parameters, Michaelis constant (K(m)) and catalytic constant (k(cat)) of
      the enzyme mediated hydrolysis of cytidine monophosphate, enabled us to classify
      stabilizing osmolytes into three different classes based on their effects on
      kinetic parameters and protein stability. (a) Polyhydric alcohols and amino acids
      and their derivatives do not have significant effects on DeltaG(D) degrees and
      functional activity (K(m) and k(cat)). (b) Methylamines increase DeltaG(D)
      degrees and k(cat), but decrease K(m). (c) Sugars increase DeltaG(D) degrees ,
      but decrease both K(m) and k(cat). These findings suggest that, among the
      stabilizing osmolytes, (a) polyols, amino acids and amino acid derivatives are
      compatible solutes in terms of both stability and function, (b) methylamines are
      the best refolders (stabilizers), and (c) sugar osmolytes stabilize the protein,
      but they apparently do not yield functionally active folded molecules.

PMID- 19765078
TI  - Donor and acceptor substrate selectivity among plant glycoside hydrolase family
      32 enzymes.
AB  - Plant family 32 glycoside hydrolase enzymes include hydrolases (cell wall
      invertases, fructan exohydrolases, vacuolar invertases) and
      fructosyltransferases. These enzymes are very similar at the molecular and
      structural levels but are functionally different. Understanding the basis of the
      functional diversity in this family is a challenging task. By combining
      structural and site-directed mutagenesis data, Asp239 in AtcwINV1 was identified
      as an amino acid critical for binding and stabilizing sucrose. Plant fructan
      exohydrolases lack such an Asp239 equivalent. Substitution of Asp239 led to the
      loss of invertase activity, while its introduction in fructan exohydrolases
      increased invertase activity. Some fructan exohydrolases are inhibited by
      sucrose. The difference between the inhibitor (fructan exohydrolase) and the
      substrate (invertase) binding configurations of sucrose can be explained by the
      different orientation of Trp82. Furthermore, the evolutionary
      hydrolase/transferase transition could be mimicked and the difference between S
      type fructosyltransferases (sucrose as donor) and F-type fructosyltransferases
      (fructan as donor) could be unravelled.

PMID- 19765079
TI  - An orphan dermaseptin from frog skin reversibly assembles to amyloid-like
      aggregates in a pH-dependent fashion.
AB  - Dermaseptin PD-3-7 (aDrs) from frog skin contains three aspartic acid residues
      resulting in a negative net charge at neutral pH, as opposed to numerous other
      dermaseptins which are cationic helical antimicrobial peptides. Still, this
      peptide can be fitted into an amphipathic alpha helix by an Edmundson wheel
      projection. However, folding to the proposed helix was induced to only a low
      extent by zwitterionic vesicles or even detergents. Furthermore, no evidence of
      antibacterial or cytotoxic activity from soluble aDrs could be obtained. The
      peptide has an inherent propensity to an extended conformation in aqueous
      solution and self-assembles into amyloid fibrils in a reversible pH-controlled
      fashion, which was studied in some detail; above pH 5, the amyloid fibrils
      disassemble in a cooperative manner. This is probably caused by deprotonation of
      both side chain and terminal carboxyl groups, which results in intermolecular
      electrostatic repulsion. At neutral pH, this process proceeds instantaneously to
      the soluble form. Within the transition interval (pH 5-6.5), however, 'backward'
      granular aggregates, 10-500 nm in size, are formed. Such metastable amorphous
      aggregates, which are quickly released from an amyloid depot by a shift in pH,
      can mediate a strong cytotoxic effect. This activity does not involve lysis or
      interference with the cellular redox status, but apparently acts via an as yet
      unidentified mechanism. In this study, we present a new member of an emerging
      class of self-assembling frog skin peptides with extraordinary self-aggregation
      properties, which may potentially be relevant for biological processes.
      Structured digital abstract: * MINT-7256467: Dermaseptin (uniprotkb:O93455) and
      Dermaseptin (uniprotkb:O93455) bind (MI:0407) by circular dichroism (MI:0016) *
      MINT-7255686: Dermaseptin (uniprotkb:O93455) and Dermaseptin (uniprotkb:O93455)
      bind (MI:0407) by biophysical (MI:0013) * MINT-7256439: Dermaseptin
      (uniprotkb:O93455) and Dermaseptin (uniprotkb:O93455) bind (MI:0407) by
      fluorescence microscopy (MI:0416) * MINT-7256449: Dermaseptin (uniprotkb:O93455)
      and Dermaseptin (uniprotkb:O93455) bind (MI:0407) by electron microscopy
      (MI:0040) * MINT-7256430: Dermaseptin (uniprotkb:O93455) and Dermaseptin
      (uniprotkb:O93455) bind (MI:0407) by fluorescence technologies (MI:0051).

PMID- 19765080
TI  - Identification of the structural determinant responsible for the phosphorylation
      of G-protein activated potassium channel 1 by cAMP-dependent protein kinase.
AB  - Besides being activated by G-protein beta/gamma subunits, G-protein activated
      potassium channels (GIRKs) are regulated by cAMP-dependent protein kinase. Back
      phosphorylation experiments have revealed that the GIRK1 subunit is
      phosphorylated in vivo upon protein kinase A activation in Xenopus oocytes,
      whereas phosphorylation was eliminated when protein kinase A was blocked. In
      vitro phosphorylation experiments using truncated versions of GIRK1 revealed that
      the structural determinant is located within the distant, unique cytosolic C
      terminus of GIRK1. Serine 385, serine 401 and threonine 407 were identified to be
      responsible for the incorporation of radioactive (32)P into the protein.
      Furthermore, the functional effects of cAMP injections into oocytes on currents
      produced by GIRK1 homooligomers were significantly reduced when these three amino
      acids were mutated. The data obtained in the present study provide information
      about the structural determinants that are responsible for protein kinase A
      phosphorylation and the regulation of GIRK channels.

PMID- 19765081
TI  - Distinct roles for NtrC and GlnK in nitrogen regulation of the Pseudomonas sp.
      strain ADP cyanuric acid utilization operon.
AB  - The Pseudomonas sp. strain ADP atzDEF operon encodes the enzymes involved in
      cyanuric acid mineralization, the final stage of the s-triazine herbicide
      atrazine degradative pathway. We have previously shown that atzDEF is under
      nitrogen control in both its natural host and Pseudomonas putida KT2442.
      Expression of atzDEF requires the divergently encoded LysR-type transcriptional
      regulator AtzR. Here, we take advantage of the poor induction of atzDEF in
      Escherichia coli to identify Pseudomonas factors involved in nitrogen control of
      atzDEF expression. Simultaneous production of P. putida NtrC and GlnK, along with
      AtzR, restored the normal atzDEF regulatory pattern. Gene expression analysis in
      E. coli and P. putida indicated that NtrC activates atzR expression, while the
      role of GlnK is to promote AtzR activation of atzDEF under nitrogen limitation.
      Activation of atzDEF in a mutant background deficient in GlnK uridylylation
      suggests that post-translational modification is not strictly required for
      transduction of the nitrogen limitation signal to AtzR. The present data and our
      previous results are integrated in a regulatory circuit that describes all the
      known responses of the atzDEF operon.

PMID- 19765082
TI  - SPM1 encoding a vacuole-localized protease is required for infection-related
      autophagy of the rice blast fungus Magnaporthe oryzae.
AB  - SPM1, encoding a putative subtilisin-like protease, is involved in pathogenicity
      of the rice blast fungus Magnaporthe oryzae, but its detailed function remains
      unknown. Here, we report that SPM1 encodes a vacuole-localized protease that is a
      critical component for autophagy during the infection process of M. oryzae.
      Detailed phenotypic analysis of targeted disruption mutants of SPM1 revealed that
      the mutants have pleiotropic defects in infection-related steps including
      germination, appressorium formation, host invasion and postinvasive growth,
      indicating the requirement of Spm1 function for the broad phase of infection. It
      has been shown that the Spm1 homolog of yeast functions in autophagy, the
      degradation machinery mediated by vacuoles, implying the involvement of Spm1 in
      autophagy in M. oryzae. In-gel protease activity assay of the recombinant Spm1
      protein indicated that Spm1 had a protease activity. An Spm1-GFP fusion protein
      was detected inside vacuoles of fungal cells, indicating that Spm1 is a protease
      localized in vacuoles. Furthermore, degradation of putative autophagic bodies was
      retarded in vacuoles of the spm1 mutant. These data strongly suggest that SPM1
      encoded protease functions in autophagy required for the pathogenicity of M.
      oryzae.

PMID- 19765083
TI  - Absence of ZnuABC-mediated zinc uptake affects virulence-associated phenotypes of
      uropathogenic Escherichia coli CFT073 under Zn(II)-depleted conditions.
AB  - In an effort to uncover the role of the high-affinity Zn(II) uptake system in
      uropathogenic Escherichia coli CFT073, we deleted the znuB gene, which encodes
      for the transmembrane component of the ZnuABC transporter system. The null mutant
      for znuB did not grow on minimal medium unless supplemented with excess Zn(II)
      (50 muM ZnCl(2)). In contrast, the E. coli K-12 DeltaznuB cell line grew well on
      minimal medium that was not supplemented with Zn(II). The DeltaznuB mutant was
      significantly deficient in the formation of biofilm under static conditions and
      also showed a substantially reduced migration front of swarm cells. Because
      motility and biofilm formation are important for E. coli CFT073 pathogenicity, we
      propose that the high-affinity Zn(II) uptake system may contribute to the
      virulence of this pathogen in the urinary tract.

PMID- 19765084
TI  - Strain-specific probiotic (Lactobacillus helveticus) inhibition of Campylobacter
      jejuni invasion of human intestinal epithelial cells.
AB  - Campylobacter jejuni is the most common bacterial cause of enterocolitis in
      humans, leading to diarrhoea and chronic extraintestinal diseases. Although
      probiotics are effective in preventing other enteric infections, beneficial
      microorganisms have not been extensively studied with C. jejuni. The aim of this
      study was to delineate the ability of selected probiotic Lactobacillus strains to
      reduce epithelial cell invasion by C. jejuni. Human colon T84 and embryonic
      intestine 407 epithelial cells were pretreated with Lactobacillus strains and
      then infected with two prototypic C. jejuni pathogens. Lactobacillus helveticus,
      strain R0052 reduced C. jejuni invasion into T84 cells by 35-41%, whereas
      Lactobacillus rhamnosus R0011 did not reduce pathogen invasion. Lactobacillus
      helveticus R0052 also decreased invasion of one C. jejuni isolate (strain 11168)
      into intestine 407 cells by 55%. Lactobacillus helveticus R0052 adhered to both
      epithelial cell types, which suggest that competitive exclusion could contribute
      to protection by probiotics. Taken together, these findings indicate that the
      ability of selected probiotics to prevent C. jejuni-mediated disease pathogenesis
      depends on the pathogen strain, probiotic strain and the epithelial cell type
      selected. The data support the concept of probiotic strain selectivity, which is
      dependent on the setting in which it is being evaluated and tested.

PMID- 19765085
TI  - Loop-mediated isothermal amplification targeting the apxIVA gene for detection of
      Actinobacillus pleuropneumoniae.
AB  - Loop-mediated isothermal amplification (LAMP) is a novel nucleic acid
      amplification method performed under isothermal conditions with high specificity
      and efficiency. We developed a diagnostic method based on LAMP for detection of
      Actinobacillus pleuropneumoniae. Using six specific primers targeting the apxIVA
      gene, the LAMP assay rapidly amplified the target gene within 30 min, requiring
      only a laboratory water bath for the reaction to occur. The resulting amplificon
      was visualized by adding SYBR Green I to the mixture. The results obtained from
      testing 15 A. pleuropneumoniae reference strains and other seven bacterial
      species strains showed that the LAMP was as specific as and 10 times more
      sensitive than nested PCR. Sixty-five tonsil samples were collected from 65
      healthy pigs. All the samples were negative for A. pleuropneumoniae by
      immunomagnetic separation-based (IMS) bacterial isolation, nested PCR and LAMP,
      respectively. Meanwhile, 115 tonsil samples were also collected from 115 pigs
      with apparent respiratory problems. Twenty-two were positive by IMS bacterial
      isolation. All the samples that were positive by IMS bacterial isolation were
      also positive by nested PCR and LAMP. The LAMP assay demonstrated exceptionally
      higher sensitivity than nested PCR by picking up 14 additional positive cases
      (chi(2) test, P<0.0001); we concluded that LAMP was a highly sensitive and
      reliable method for detection of A. pleuropneumoniae infection.

PMID- 19765086
TI  - Correlative effect on the toxicity of three surface-exposed loops in the receptor
      binding domain of the Bacillus thuringiensis Cry4Ba toxin.
AB  - Surface-exposed loop residues, Pro(389) (beta(6)-beta(7) loop), Glu(417) (beta(8)
      beta(9) loop), Tyr(455) and Asn(456) (beta(10)-beta(11) loop), in the receptor
      binding domain of the Bacillus thuringiensis Cry4Ba toxin have been previously
      demonstrated to be crucial for toxicity. Herein, five combinations of two-loop
      mutants, P389A/E417A (beta(6)-beta(7)/beta(8)-beta(9) loops), P389A/Y455A,
      P389A/N456A (beta(6)-beta(7)/beta(10)-beta(11) loops), E417A/Y455A and
      E417A/N456A (beta(8)-beta(9)/beta(10)-beta(11) loops), were constructed as a
      means of examining a correlative effect of these three critical loops on Cry4Ba
      toxicity. All 130-kDa mutant protoxins were overexpressed as inclusion bodies in
      Escherichia coli with yields comparable to the wild-type toxin. In addition, all
      mutant toxins were structurally stable upon solubilization and trypsin activation
      in carbonate buffer, pH 9.0. Interestingly, E. coli cells expressing all the
      double-loop mutants showed an almost complete loss in toxicity against Aedes
      aegypti mosquito larvae while their corresponding single-loop mutants exhibited
      reduced activity of approximately 50%. Moreover, in situ binding analysis
      revealed that the 65-kDa purified toxins representing each pairwise mutant
      exhibited reduced binding to apical microvilli of A. aegypti larval midgut when
      compared with the single mutants. Altogether, the data demonstrate for the first
      time that all these three surface-exposed loops of the Cry4Ba toxin are equally
      involved in receptor binding and hence toxicity.

PMID- 19765087
TI  - Glycogen phosphorylase is involved in stress endurance and biofilm formation in
      Azospirillum brasilense Sp7.
AB  - Here we report the identification of a glycogen phosphorylase (glgP) gene in the
      plant growth-promoting rhizobacterium Azospirillum brasilense, Sp7, and the
      characterization of a glgP marker exchange mutant of this strain. The glgP mutant
      showed a twofold reduction of glycogen phosphorylase activity and an increased
      glycogen accumulation as compared with wild-type Sp7, indicating that the
      identified gene indeed encodes a protein with glycogen phosphorylase activity.
      Interestingly, the glgP mutant had higher survival rates than the wild type after
      exposure to starvation, desiccation and osmotic pressure. The mutant was shown to
      be compromised in its biofilm formation ability. Analysis of the
      exopolysaccharide sugar composition of the glgP mutant revealed a decrease in the
      amount of glucose, accompanied by increases in rhamnose, fucose and ribose, as
      compared with the Sp7 exopolysaccharide. To the best of our knowledge, this is
      the first study that demonstrates GlgP activity in A. brasilense, and shows that
      glycogen accumulation may play an important role in the stress endurance of this
      bacterium.

PMID- 19765088
TI  - Glycosyltransferases and oligosaccharyltransferases in Archaea: putative
      components of the N-glycosylation pathway in the third domain of life.
AB  - The ability of Eukarya, Bacteria and Archaea to perform N-glycosylation underlies
      the importance and possible antiquity of this post-translational protein
      modification. However, in contrast to the relatively well-studied eukaryal and
      bacterial pathways, the archaeal N-glycosylation process is less understood. To
      remedy this disparity, the following study has examined 56 available archaeal
      genomes with the aim of identifying glycosyltransferases and
      oligosaccharyltransferases, including those putatively catalyzing this post
      translational processing event. This analysis reveals that while
      oligosaccharyltransferases, central components of the N-glycosylation pathway,
      are found across the range of archaeal phenotypes, the N-glycosylation machinery
      of hyperthermophilic Archaea may well rely on fewer components than do the
      parallel systems of nonhyperthermophilic Archaea. Moreover, genes encoding
      predicted glycosyltransferases of hyperthermophilic Archaea tend to be far more
      scattered within the genome than is the case with nonhyperthermophilic species,
      where putative glycosyltransferase genes are often clustered around identified
      oligosaccharyltransferase-encoding sequences.

PMID- 19765089
TI  - Three anamorphic yeast species Candida sanitii sp. nov., Candida sekii sp. nov.
      and Candida suwanaritii, three novel yeasts in the Saturnispora clade isolated in
      Thailand.
AB  - Nine strains of three novel anamorphic yeast species were obtained from samples
      collected in Thailand including six strains (RV96, RV152, R14, RS9, RS58 and EA1)
      obtained from estuarine waters collected from two mangrove forests, one strain
      (ST84) from insect frass and two strains (SR16 and UB13) from forest soils. On
      the basis of morphological, biochemical, physiological and chemotaxonomic
      characteristics, and the sequence analysis of the D1/D2 domain of the large
      subunit rRNA gene, the nine strains were found to represent three novel Candida
      species in the Saturnispora clade. Five strains (RV96, RV152, R14, RS9 and RS58)
      were assigned as a single novel species, which was named Candida sanitii sp. nov.
      The type strain is RV152(T) (BCC 25967(T)=NBRC 103864(T)=CBS 10864(T)). Strain
      EA1 was named as Candida suwanaritii sp. nov. The type strain is EA1(T) (BCC
      29900(T)=NBRC 104877(T)=CBS 11021(T)). Three strains (ST84, SR16 and UB13)
      represented another novel species, for which Candida sekii sp. nov. is proposed.
      The type strain is ST84(T) (BCC 8320(T)=NBRC 105671(T)=CBS 10931(T)).

PMID- 19765090
TI  - Two proteins from Saccharomyces cerevisiae: Pfy1 and Pkc1, play a dual role in
      activating actin polymerization and in increasing cell viability in the adaptive
      response to oxidative stress.
AB  - In this work, we show that the proteins Pkc1 and Pfy1 play a role in the
      repolarization of the actin cytoskeleton and in cell survival in response to
      oxidative stress. We have also developed an assay to determine the actin
      polymerization capacity of total protein extracts using fluorescence recovery
      after photobleaching techniques and actin purified from rabbit muscle. This assay
      allowed us to demonstrate that Pfy1 promotes actin polymerization under
      conditions of oxidative stress, while Pkc1 induces actin polymerization and cell
      survival under all the conditions tested. Our assay also points to a relationship
      between Pkc1 and Pfy1 in the actin cytoskeleton polymerization that is required
      to adapt to oxidative stress.

PMID- 19765091
TI  - Pregnancy in a patient with severe factor X deficiency.

PMID- 19765092
TI  - In vitro and in vivo stability of diluted recombinant factor VIII for continuous
      infusion use in haemophilia A.
AB  - Factor VIII (FVIII) replacement by continuous infusion (CI) is used
      postoperatively or after significant bleeding. For young paediatric patients, CI
      may require FVIII dilution. Variable stabilities of diluted full-length
      recombinant FVIII Kogenate FS (KG-FS) have been reported under different storage
      conditions. We investigated the recovery and stability of diluted KG-FS in vitro
      and in vivo. Kogenate FS was diluted to 50-120 U mL(-1) and its recovery and
      stability in glass vials or polypropylene syringes was determined. Furthermore,
      stability of KG-FS diluted to 80 U mL(-1)'administered' via single- and double
      pump mock CI systems was tested. Finally, the in vivo stability of KG-FS diluted
      to approximately 60 U mL(-1) and administered postsurgically by CI with the
      double-pump to a paediatric patient with severe haemophilia A undergoing
      implantable venous access device placement was investigated. Initial KG-FS
      dilution resulted in a 10-20% FVIII loss; a further 25-30% loss occurred over 72
      h in vials or syringes. With the double-pump, 1 h recovery was 35%, increasing to
      80% by 24 h; the initial losses were because of the Y-infusion of a 10-fold
      larger volume of saline concomitantly with the FVIII. In vivo, CI resulted in
      stable FVIII activity levels within the target range. These in vitro results are
      important for the generation of CI guidelines for diluted KG-FS in the paediatric
      haemophilic population. That FVIII losses occur upon dilution and with the double
      pump does not preclude use of diluted KG-FS. Indeed, stable FVIII levels were
      maintained when diluted KG-FS was administered by CI with the double-pump to a
      paediatric patient postsurgically.

PMID- 19765093
TI  - Genetic analysis for some plant and fruit traits, and its implication for a
      breeding program of hot pepper (Capsicum annuum var. annuum L.).
AB  - Two separate field experiments were conducted on hot pepper in which the genetic,
      heritability and environmental components of variation for seven plant and fruit
      traits in 78 genotypes and gene effects for four fruit traits in six generations
      of five crosses were estimated. The objectives were to determine the variation
      and effects of genes controlling inheritance of plant and fruit traits, and to
      propose efficient breeding procedures for improving the crop. Analysis of
      variance in half-diallel crosses revealed the presence of total genetic
      variability for seven traits among the 78 experimental entries with an excess of
      over-dominance genes. The presence of unequal distributions of dominant genes
      with positive and negative effects was observed among the parents and indicated
      the need to be cautious while selecting hot pepper parents for breeding purposes.
      Significant variability was also revealed in environmental sensitivity among the
      78 experimental entries for some traits along with high heritability, which could
      be an advantage for a plant breeder but provides less clear opportunities for an
      agronomist to achieve better plant and fruit traits. Progeny generations (F(1),
      F(2), B(1) and B(2)) were found to perform better for fruit traits than their
      parents (P(1) and P(2)). The presence of significant gene interactions indicated
      a polygenic inheritance of the fruit traits studied and the possibility of
      pyramiding favorable alleles in the required directions at different levels of
      progeny generations. Heterosis, backcrossing, multiple crossing and pedigree
      breeding methods with recurrent selection may facilitate simultaneous
      exploitation of the genetic components and gene effects obtained. Nevertheless,
      it is doubtful whether selection efforts within the current set of hot pepper
      parents would be beneficial to achieve superior fruit traits for developing new
      varieties.

PMID- 19765094
TI  - Unusual intra-individual karyotypical variation and evidence of cryptic species
      in Amazonian populations of Pristimantis (Anura, Terrarana).
AB  - We report a cytogenetic analysis of three Pristimantis fenestratus frog
      populations of the Amazon region in Brazil. The specimens were sampled in Borba
      and Manaus, Amazonas State, and in Rio Branco, Acre State. They were analyzed
      using Giemsa, silver staining, C-banding and FISH with rDNA probes. The
      karyotypes of the three populations revealed 2n = 34 chromosomes, but they
      differed in the number and position of Ag-NORs and in the heterochromatin pattern
      as well. The NOR was located on the pairs 05 and 07 in the Rio Branco specimens,
      pair 10 in the Manaus specimens, and pair 1 in the Borba specimens. A small C
      band was detected on the telomeric region of the pair 05 in the Borba population,
      while in the Manaus there was a heterochromatic block adjacent to the centromere
      of pair 9. An unusual intra-individual variation of chromosome number was
      observed in metaphases of Rio Branco specimens, comprising fundamental numbers of
      33, 34 and 35. Additionally, interchromosome thread connections were detected
      between telomere - telomere, centromere - telomere and centromere - centromere
      regions, and among chromosomal heterochromatin-rich sites. The NOR sites were
      also involved in those connections. We hypothesize that this variation is due to
      chromosome missegregation during mitosis. The inter- and intraindividual
      variation in chromosome number suggests chromosomal instability in P.
      fenestratus, which has not been detected in any other anuran group. Since Borba
      is the type-locality of P. fenestratus, a taxonomic review of the Manaus and Rio
      Branco populations should be done, as indicated by the cytogenetic evidence that
      they could be new species of Pristimantis.

PMID- 19765095
TI  - Cytogenetic studies of three European species of Centaurea L. (Asteraceae).
AB  - Cytogenetic analysis of several populations of Centaurea jacea (2n = 4x = 44), C.
      oxylepis (2n = 4x = 44) and C. phrygia (2n = 2x = 22) was performed using flow
      cytometry, differential chromosome staining and FISH. In all species Arabidopsis
      type telomeric repeats hybridized only to the terminal part of chromosomes. In C.
      phrygia three pairs and in C. oxylepis six pairs of chromosomes revealed the
      hybridization signals of 45S rDNA. Centaurea jacea showed polymorphism in the 45S
      rDNA loci number, five or six pairs of sites were observed. 5S rDNA loci were
      located in two pairs of chromosomes in C. phrygia. In C. jacea and C. oxylepis
      the number and position of 5S rDNA loci were the same: three pairs located
      interstitially and one terminally. The genome size of the diploid C. phrygia was
      established as 2.14 pg/2C. The genomes of tetraploid species were nearly two
      times larger and genome size polymorphism was observed among C. jacea
      populations.

PMID- 19765096
TI  - The effect of the mus309 mutation, defective in DNA double-strand break repair,
      on crossing over in Drosophila melanogaster suggests a mechanism for
      interference.
AB  - The mus309 gene in Drosophila melanogaster encodes a RecQ helicase which is
      involved in DNA double-strand break (DSB) repair. In a brood pattern analysis, it
      was observed that in mus309 mutant females, the frequency of single crossovers in
      the central cv - v interval of the X chromosome was decreased in young females
      but returned to the level of the wild type control as the females aged. In the
      proximal v - f interval, the frequency of single crossovers was increased during
      the whole experimental period. In particular, it was observed that the frequency
      of double crossovers, as well as the coefficient of coincidence first increased
      but then gradually decreased, finally reaching the level of the control flies, as
      the females aged. Map distances increased due to the mus309 mutation in both gene
      interval studies, but they did not change as the females aged, a result
      suggesting that the mus309 gene controls the distribution of DSBs to be repaired
      as crossovers instead of non-crossovers. The results are consistent with the
      hypothesis that in general the DSBs are initially independently distributed on
      the chromosome but non-randomly repaired so that the distribution of crossovers
      in the mutant flies becomes uniform, but uneven in wild-type flies. The results
      are consistent with the counting number model of crossover interference, based on
      genetic distance. On the other hand, the data are not consistent with the
      reaction-diffusion model based on physical distance. Consequently, the view that
      crossover interference in Drosophila is tightly tied to genetic distance is
      supported.

PMID- 19765097
TI  - Chromosomal assignment of equine genes involved in the development of skeletal,
      gastrointestinal, cardiovascular and nervous system.

PMID- 19765098
TI  - Micromanipulation reveals an XO-XX sex determining system in the orb-weaving
      spider Neoscona arabesca (Walckenaer).
AB  - Karyotypes can be difficult to create due to odd chromosome behaviors and high
      levels of adhesion between sex chromosomes. We have used live-cell imaging and
      micromanipulation to determine precisely the karyotype of the orb-weaving spider
      Neoscona arabesca (Walckenaer). We have found that N. arabesca has a sex
      determination mechanism of XO (male)-XX (female) with 2n = 20 autosomes. Staining
      of female tissues revealed a chromosome number of 22 in mitotic cells.

PMID- 19765099
TI  - Phantom testis syndrome: prevalence, phenomenology and putative mechanisms.
AB  - Chronic phantom pain has been found in up to 78% of limb amputees and is a major
      complication of limb amputation. Less is known about phantom phenomena after the
      amputation of other, i.e. visceral, parts of the body. In a retrospective design,
      we identified 539 patients in whom one testis was removed between 1995 and 2005.
      The operative technique was a unilateral standard radical inguinal orchiectomy.
      The underlying pathology in all cases was a testicular germ cell tumour. All
      patients received a detailed questionnaire asking about the occurrence of phantom
      testis pain (pain felt in the removed testis), phantom testis sensations (non
      painful sensations as if the removed testis was still intact) and hallucinations
      (illusionary perceptions on the removed testis). Furthermore, we asked about the
      occurrence and clinical presentation of pain before and after surgery and about
      pre-operative testicular pain. Out of 238 respondents, 125 patients (53%)
      reported any kind of phantom experience. The prevalence of phantom testis pain
      was 25% (60/238), non-painful phantom sensations 16% (37/238) and male gonad
      hallucinations 12% (28/238). Patients with phantom symptoms reported pre
      operative pain in the removed testis more often than patients without phantom
      symptoms. This study presents first data on the clinical characteristics and
      possible mechanisms of the phantom testis syndrome after surgical removal of one
      testis.

PMID- 19765100
TI  - A systematic approach to the investigation and diagnosis of a unilateral pleural
      effusion.
AB  - Fluid in the pleural space is a common sequela of a wide range of diseases which
      may be pulmonary, pleural or extrapulmonary. As the differential diagnosis is
      wide, a systematic approach to investigation and diagnosis is recommended. This
      review highlights the important features and recommendations for the
      investigation of a unilateral pleural effusion, a common condition encountered by
      the general physician. The aim of this study was to assist with a speedy
      diagnosis of the underlying pathology, using appropriate investigative
      techniques, while minimising the use of invasive procedures.

PMID- 19765101
TI  - Analysing the role of endogenous matrix molecules in the development of
      osteoarthritis.
AB  - Osteoarthritis (OA) is the most common form of arthritis worldwide. In this
      condition, damage to the extracellular matrix (ECM) of cartilage occurs,
      resulting in joint destruction. Factors mediating cartilage damage include
      mechanical injury, cytokine and superoxide release on a background of genetic
      susceptibility and obesity. Studies of arthritic cartilage show increased
      production of ECM molecules including type II collagen, cartilage oligomeric
      matrix protein, fibronectin (FN) and fibromodulin. Recent reports suggest that
      ECM proteins may become endogenous catabolic factors during joint damage.
      Activation of pro-inflammatory pathways by ECM proteins has led to their
      description as damage-associated molecular patterns (DAMPs). The ECM proteins
      involved include fibromodulin, which activates the complement pathway and may
      promote the persistence of joint inflammation. Fragmentation of type II collagen,
      FN and hyaluronan reveals cryptic epitopes that stimulate proteolytic enzymes
      including matrix metalloproteinases and aggrecanases (ADAMTSs - a disintegrin and
      metalloproteinase with thrombospondin type 1 motifs). Proteolytic fragments also
      stimulate the release of nitric oxide, chemokines and cytokines and activation of
      the MAP kinases. Reports are emerging that the receptors for the fragments
      described involve interaction with integrins and toll-like receptors. In this
      review the contribution of endogenous ECM molecules to joint destruction will be
      discussed. A deeper understanding of the pathways stimulated by endogenous
      ligands could offer potential avenues for novel therapies in the future.

PMID- 19765102
TI  - Otitis media in a mouse model for Down syndrome.
AB  - The Ts65Dn mouse shares many phenotypic characteristics of human Down syndrome.
      Here, we report that otitis media, characterized by effusion in the middle ear
      and hearing loss, was prevalent in Ts65Dn mice. Of the 53 Ts65Dn mice tested,
      81.1% had high auditory-evoked brainstem response (ABR) thresholds for at least
      one of the stimulus frequencies (click, 8 kHz, 16 kHz and 32 kHz), in at least
      one ear. The ABR thresholds were variable and showed no tendency toward increase
      with age, from 2 to 7 months of age. Observation of pathology in mice, aged 3-4
      months, revealed middle ear effusion in 11 of 15 Ts65Dn mice examined, but only
      in two of 11 wild-type mice. The effusion in each mouse varied substantially in
      volume and inflammatory cell content. The middle ear mucosae were generally
      thickened and goblet cells were distributed with higher density in the epithelium
      of the middle ear cavity of Ts65Dn mice as compared with those of wild-type
      controls. Bacteria of pathogenic importance to humans also were identified in the
      Ts65Dn mice. This is the first report of otitis media in the Ts65Dn mouse as a
      model characteristic of human Down syndrome.

PMID- 19765103
TI  - Irinotecan-induced mucositis manifesting as diarrhoea corresponds with an amended
      intestinal flora and mucin profile.
AB  - Chemotherapy-induced diarrhoea is a major oncological problem, caused by the
      cytotoxic effects of cancer chemotherapy. Irinotecan is linked with severe
      mucositis and diarrhoea, the mechanisms of which remain poorly understood.
      Bacterial beta-glucuronidase is thought to be involved in the metabolism of
      irinotecan, implicating the intestinal flora. Intestinal mucins may also be
      implicated in the development of chemotherapy-induced diarrhoea. Rats were
      treated with 200 mg/kg of irinotecan and killed at 96, 120 and 144 h. The rats
      were monitored for diarrhoea. Pathology and immunohistochemical staining was
      performed. The samples were cultured and faecal DNA was analysed using real-time
      polymerase chain reaction. Severe diarrhoea was observed from 72 to 96 h. A
      decrease in body mass was also observed after treatment. Significant changes in
      goblet cell numbers (both complete and cavitated cells) were observed in the
      small and large intestines. Changes in MUC gene expression were observed in the
      small intestine only. Modifications were observed to the intestinal flora
      profile, especially Escherichia coli, and an increase in the expression of beta
      glucuronidase was detected. In conclusion, irinotecan-induced diarrhoea may be
      caused by an increase in some beta-glucuronidase-producing bacteria, especially
      E. coli, exacerbating the toxicity of active metabolites. Accelerated mucous
      secretion and mucin release may also contribute to the delayed onset of
      diarrhoea.

PMID- 19765104
TI  - Dose response and time course studies on superoxide dismutase as a urinary
      biomarker of carbon tetrachloride-induced hepatic injury in the Hanover Wistar
      rat.
AB  - Previous studies have shown that the enzyme copper/zinc superoxide dismutase (SOD
      1) is increased in the urine of rats with carbon tetrachloride (CCl(4))-induced
      hepatotoxicity. The present experiments aimed to investigate further the
      usefulness of urinary SOD-1 as a non-invasive biomarker of liver injury. Two
      investigations were carried out, a dose response study and a time course study.
      In the dose response study, rats were given a single dose of CCl(4) at 0
      (control), 0.10, 0.15, 0.20, 0.25, 0.30, 0.35, 0.40 and 0.80 ml/kg and urine
      samples collected from 12 to 36 h postdosing. In the time course study, rats were
      dosed at 0.80 ml/kg CCl(4) and urine sampled at 4, 12, 24 and 36 h postdosing. In
      both studies, the presence of SOD-1 in the urine was confirmed by Western
      blotting with an SOD-1 antibody. In the dose response study, serum SOD activity
      was elevated in all CCl(4)-treated animals and urinary SOD-1 activity was
      increased 2.2 times at the lowest dose (0.10 ml/kg) and 60.4 times at the highest
      CCl(4) dose level (0.80 ml/kg). In the time course study, urinary SOD-1 was first
      detected in samples collected from 4 to 12 h postdosing. We conclude that urinary
      SOD-1 has potential as a sensitive non-invasive biomarker of CCl(4)-induced
      hepatocellular injury.

PMID- 19765105
TI  - Ovariectomy-associated changes in bone mineral density and bone marrow
      haematopoiesis in rats.
AB  - The relationship between the bone mass loss and bone marrow haematopoiesis in
      osteoporosis remains obscure. We selected 3-month-old female Sprague-Dawley rats
      and randomly divided them into six groups. Three groups were ovariectomized
      (OVX), while the other three groups were sham operated (Sham). Four, 8 and 12
      weeks after the surgical procedure, the rats were euthanized and sampled. The
      left femur was used for measurement of bone mineral density (BMD). The right
      femur distal metaphysic cancellous bone was processed for morphological
      evaluation. Our results showed that the femur BMD in the 4-week OVX group was not
      significantly decreased compared with that of the 4-week Sham group, but that the
      volume of adipose tissue in the bone marrow was markedly increased. The femur BMD
      in the 8-week OVX group was decreased significantly compared with that of the 8
      week Sham group (P < 0.05). Meanwhile, the volume of haematopoietic tissue
      decreased and the volume of adipose tissue increased. The number of
      megakaryocytes was decreased (P < 0.05). Interestingly, the osteoclasts and mast
      cells were increased in number in the 8-week OVX group (P < 0.05). These changes
      became obvious in the 12-week OVX rats, in contrast to the Sham groups. The
      volume of trabecular bone and the number of osteoblasts in the 12-week OVX group
      decreased significantly. Increased reticulin fibres were observed only in the 12
      week OVX group. Our studies demonstrated a reciprocal correlation between bone
      forming osteoblasts and marrow adipose tissue and suggest that OVX rats may be
      valuable as an animal model to study hypohaemopoiesis.

PMID- 19765106
TI  - Femur bone repair in ovariectomized rats under the local action of alendronate,
      hydroxyapatite and the association of alendronate and hydroxyapatite.
AB  - Summary An evaluation was made of the local action of alendronate sodium (A),
      hydroxyapatite (HA) and the association of both substances (A + HA), in different
      molar concentrations, on the femur bone repair of ovariectomized rats. Ninety
      eight animals were divided into seven groups: control (C), starch (S),
      alendronate 1 mol (A1), alendronate 2 mols (A2), hydroxyapatite 1 mol (HA1),
      hydroxyapatite 2 mols (HA2) and the association of alendronate + hydroxyapatite
      (A + HA). Rats weighing about 250 g were ovariectomized and 2.5-mm diameter bone
      defects were made on the left femur 30 days later. Each experimental group had
      defects filled with appropriate material, except for group C (control). The
      animals were killed 7 and 21 days after surgery. Histological, histomorphometric
      and statistical analyses of bone neoformation in the bone defect site were
      performed. From the histological standpoint, the major differences occurred after
      21 days. All specimens in groups C, S, HA1 and HA2 presented linear closure of
      the bone defect, and most animals in groups A1, A2 and A + HA showed no bone
      neoformation in the central area of the defect. No statistically significant
      difference was found among the experimental groups after 7 days; after 21 days,
      group HA2 presented the highest amount of neoformed bone. There was no
      significant difference among groups A1, A2 and A + HA in the two study periods.
      It was concluded that alendronate, either isolated or in association with
      hydroxyapatite, had an adverse effect on bone repair in this experimental model.
      Moreover, the hydroxyapatite used here proved to be biocompatible and
      osteoconductive, with group HA2 showing the best results.

PMID- 19765107
TI  - Matrix metalloproteinases with gelatinolytic activity induced by Paracoccidioides
      brasiliensis infection.
AB  - Matrix metalloproteinases (MMPs) modulate extracellular matrix turnover,
      inflammation and immunity. We studied MMP-9 and MMP-2 in experimental
      paracoccidioidomycosis. At 15 and 120 days after infection (DAI) with virulent
      Paracoccidioides brasiliensis, MMP-9 was positive by immunohistochemistry in
      multinucleated giant cells, in mononuclear cells with macrophage and lymphocyte
      morphologies and also in fungal cells in the lesions of susceptible and resistant
      mice. Using gelatin zymography, pro- and active MMP-9 and active MMP-2 were
      detected in all infected mice, but not in controls. Gelatinolytic activity was
      not observed in P. brasiliensis extracts. Semiquantitative analysis of
      gelatinolytic activities revealed weak or absent MMP-2 and strong MMP-9 activity
      in both mouse strains at 15 DAI, declining at 120 DAI. Avirulent P. brasiliensis
      infected mice had residual lesions with MMP-9-positive pseudoxantomatous
      macrophages, but no gelatinase activity at 120 DAI. Our findings demonstrate the
      induction of MMPs, particularly MMP-9, in experimental paracoccidioidomycosis,
      suggesting a possible influence in the pattern of granulomas and in fungal
      dissemination.

PMID- 19765108
TI  - Hepatic extracellular matrix alterations in dogs naturally infected with
      Leishmania (Leishmania) chagasi.
AB  - Summary The aim of this work was to study alterations in the extracellular matrix
      of liver in dogs naturally infected with Leishmania (Leishmania) chagasi that are
      correlated with clinical aspects and with histological, parasitological and
      immunological findings. The study was carried out on 30 dogs, 10 uninfected
      (control group) and 20 infected. The infected animals were further divided into
      two groups: an asymptomatic group of 10 dogs without clinical signs of the
      disease; and a symptomatic group of 10 dogs with classical clinical signs. All
      thirty animals were mongrel dogs of undefined age, obtained from the municipality
      of Belo Horizonte, MG, metropolitan area. During necropsy, liver fragments were
      collected and fixed in 10% buffered formaldehyde for histological examination.
      Paraffined sections of the tissues were stained with haematoxylin-eosin, Gomori's
      ammoniacal silver stain for reticular fibres and strepto-avidin peroxidase for
      immunohistochemical detection of Leishmania amastigotes. Frozen tissue sections
      were stained by immunofluorescence for fibronectin (FN) and laminin (LN). Liver
      collagen deposition was significantly greater in the infected than the control
      animals and differed significantly between the symptomatic and asymptomatic dogs.
      There was a positive correlation between the parasite load and liver collagen
      deposition. The increased collagen deposition in infected animal livers may be
      associated with the parasite burden. Adhesive FN and LN fibres were significantly
      more highly expressed in the livers of symptomatic than of asymptomatic dogs. Our
      results demonstrate that canine visceral leishmaniasis causes fibrogenesis in
      liver, associated with the parasite load and degenerative processes.

PMID- 19765109
TI  - Common genetic changes in leiomyosarcoma and gastrointestinal stromal tumour:
      implication for ataxia telangiectasia mutated involvement.
AB  - Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours
      of the gastrointestinal tract. Formerly GISTs were commonly classified
      histologically as leiomyosarcomas; however, they are now known to arise from the
      interstitial cells of Cajal. Majority of GISTs overexpress KIT and have
      characteristic mutations within the gene, which are the targets of drug treatment
      with tyrosine kinase inhibitors. Leiomyosarcoma is a malignant tumour of smooth
      muscle differentiation and falls into a group of sarcomas that show complex
      karyotypic changes with no consistent recurrent genetic abnormality. We have used
      comparative genomic hybridization in combination with fluorescence in situ
      hybridization to determine genetic differences between the tumour types. We found
      leiomyosarcomas and GISTs share common regions of chromosomal 13q and 11q
      imbalance, in addition to more specific 1p and 8p losses in leiomyosarcoma and
      15q and 22q losses in GISTs. More importantly, we have shown for the first time a
      deletion in the ataxia telangiectasia mutated (ATM) gene locus with
      decreased/absent expression of ATM protein, and amplification in the region 13q21
      q32 in both tumour types, suggesting both regions may play a role in
      leiomyosarcoma and GIST biology.

PMID- 19765110
TI  - Mutated K-ras(Asp12) promotes tumourigenesis in Apc(Min) mice more in the large
      than the small intestines, with synergistic effects between K-ras and Wnt
      pathways.
AB  - Summary K-ras mutations are found in 40-50% of human colorectal adenomas and
      carcinomas, but their functional contribution remains incompletely understood.
      Here, we show that a conditional mutant K-ras mouse model (K-ras(Asp12)/Cre),
      with transient intestinal Cre activation by beta-Naphthoflavone (beta-NF)
      treatment, displayed transgene recombination and K-ras(Asp12) expression in the
      murine intestines, but developed few intestinal adenomas over 2 years. However,
      when crossed with Apc(Min/+) mice, the K-ras(Asp12)/Cre/Apc(Min/+) offspring
      showed acceleration of intestinal tumourigenesis with significantly changed
      average lifespan (P < 0.05) decreased to 18.4 +/- 5.4 weeks from 20.9 +/- 4.7
      weeks (control Apc(Min/+) mice). The numbers of adenomas in the small intestine
      and large intestine were significantly (P < 0.01) increased by 1.5-fold and 5.7
      fold, respectively, in K-ras(Asp12)/Cre/Apc(Min/+) mice compared with Apc(Min/+)
      mice, with the more marked increase in adenoma prevalence in the large intestine.
      To explore possible mechanisms for K-ras(Asp12) and Apc(Min) co-operation, the
      Mitogen-activated protein kinase (Mapk), Akt and Wnt signalling pathways,
      including selected target gene expression levels, were evaluated in normal large
      intestine and large intestinal tumours. K-ras(Asp12) increased activation of Mapk
      and Akt signalling pathway targets phospho-extracellular signal-regulated kinase
      (pErk) and pAkt, and increased relative expression levels of Wnt pathway targets
      vascular endothelial growth factor (VEGF), gastrin, cyclo-oxygenase 2 (Cox2) and
      T-cell lymphoma invasion and metastasis 1 (Tiam1) in K-ras(Asp12)/Cre/Apc(Min/+)
      adenomas compared with that of Apc(Min/+) adenomas, although other Wnt signalling
      pathway target genes such as Peroxisome proliferator-activated receptor delta
      (PPARd), matrix metalloproteinase 7 (MMP7), protein phosphatase 1 alpha (PP1A)
      and c-myc remained unchanged. In conclusion, intestinal expression of K
      ras(Asp12) promotes mutant Apc-initiated intestinal adenoma formation in vivo
      more in the large intestine than the small intestine, with evidence of
      synergistic co-operation between mutant K-ras and Apc involving increased
      expression of some Wnt-pathway target genes.

PMID- 19765111
TI  - An evaluation of the SPIFE 3000 semi-automated gel electrophoresis system for the
      identification of hemoglobin variants and comparison of relative electrophoretic
      mobilities with manual gel electrophoresis methods.
AB  - Laboratory identification of hemoglobin (Hb) variants can involve multiple
      techniques. The use of semi-automated instruments that perform gel
      electrophoresis and staining, such as the SPIFE 3000 electrophoresis system, can
      greatly reduce the labor required for these commonly used techniques. We
      performed a comparison of the method involved in SPIFE 3000 system with those of
      manual gel electrophoresis. A total of 22 540 samples were analyzed using the
      SPIFE 3000, and compared with mobilities on cellulose acetate and citrate agar
      gels using standard manual methods. The results were compared using relative
      electrophoretic mobilities (REM). Of the 191 Hb variants identified, only 13 had
      REM that differed from manual electrophoresis when analyzed using the SPIFE 3000
      system. One variant (Hb O-Indonesia) showed different mobility on both acid and
      alkaline gels, two (Hb E, Hb Sunshine Seth) on alkaline gel only, and 10 (Hbs N
      Baltimore, N-Seattle, O-Arab, Shelby, Summer Hill, Tak, Hasharon, M-Iwate, Q
      Iran, and Setif) on acid gels only. The SPIFE 3000 semi-automated electrophoresis
      system produces similar results when compared with those of standard manual
      electrophoresis methods.

PMID- 19765112
TI  - Stroke: what can you do?

PMID- 19765113
TI  - The World Stroke Organisation and the World Stroke Day.

PMID- 19765114
TI  - WorldStroke Day 2009.

PMID- 19765115
TI  - Reprint: what can I do?

PMID- 19765116
TI  - Poststroke service in Poland: results of a 2-year prospective, observational
      study.

PMID- 19765117
TI  - Intravenous thrombolysis is feasible and safe in multiethnic Asian stroke
      patients in Singapore.

PMID- 19765118
TI  - Incidence and case fatality of subarachnoid haemorrhage in Northern Greece: the
      Evros Registry of Subarachnoid Haemorrhage.
AB  - BACKGROUND: Epidemiological data on subarachnoid haemorrhage incidence and case
      fatality rates are scarce in the south-eastern Mediterranean region. We conducted
      a population-based study in Evros Province, located in north-eastern Greece, to
      determine subarachnoid haemorrhage incidence over a 5-year period (2001-2005).
      METHODS: Evros Province has a well-defined, largely homogeneous population with
      healthcare organised around a single tertiary-care University Hospital. We
      organised a prospective computerised registry of permanent Evros residents
      admitted or transferred to our hospital with a diagnosis of subarachnoid
      haemorrhage. Standard World Health Organization definitions and overlapping case
      finding methods were used to identify all cases of first ever in a lifetime
      subarachnoid haemorrhage in all age groups, occurring during the study period.
      The diagnosis was confirmed by computed tomography scan in all hospitalised
      cases. Sudden deaths attributable to subarachnoid haemorrhage were systematically
      recorded province-wide by our forensic department and are included in the study.
      RESULTS: During the 5-year period, 51 cases of subarachnoid haemorrhage were
      recorded (28 men, 23 women; mean age 59+/-17 years). The crude annual incidence
      rates were 8.3/100,000 persons (95% confidence interval: 5.5-12.0) for men,
      7.5/100,000 (4.8-11.3) for women and 7.9/100,000 (5.9-10.4) for all subjects. The
      standardised incidence rates for groups aged 45-84 years in the European
      population were 9.3/100,000 (5.8-12.8) for men, 6.5/100,000 (3.7-9.4) for women
      and 7.9/100,000 (5.7-10.2). The 28-day case-fatality rates for men, women and all
      subjects were 36% (21-54%), 35% (19-55%) and 35% (24-49%), respectively.
      CONCLUSIONS: The incidence and case-fatality rate of subarachnoid haemorrhage
      haemorrhage in Greece appear to be similar to other developed countries. No
      gender differences in subarachnoid haemorrhage incidence and case-fatality rate
      were documented.

PMID- 19765119
TI  - Pre admission antithrombotics are associated with improved outcomes following
      ischaemic stroke: a cohort from the Registry of the Canadian Stroke Network.
AB  - BACKGROUND: Several studies have attempted to identify predictors of outcome
      following ischaemic stroke. Reduced stroke severity has been reported with pre
      admission ASA use, and improved outcomes have been reported with pre admission
      statin treatment. The interaction between pre treatment medications and clinical
      response to tPA is less clear. The objective of our study was to assess clinical
      outcomes in patients with acute ischaemic stroke with respect to pre treatment
      medications. METHODS: The Registry of the Canadian Stroke Network collected pre
      morbid and prospective outcome data on 5568 patients with ischaemic stroke. We
      applied multivariate analyses to correlate pre admission medications with stroke
      severity on presentation, in-hospital mortality, and modified Rankin at
      discharge. Analyses were adjusted for age, gender, medical history, tPA
      administration, blood pressure, and glucose on presentation. RESULTS: Pre
      admission treatment with ASA and clopidogrel was associated with less severe
      stroke upon presentation. A similar trend was seen with dipyridamole and
      ticlopidine, but did not reach statistical significance. Pre treatment with ASA
      and warfarin was associated with improved Rankin scores at discharge. There was
      no interaction between tPA treatment and pre admission antiplatelets with respect
      to in-hospital mortality or disability at discharge, although tPA treatment was
      independently associated with improved Rankin at discharge. Pre treatment
      antiplatelet use did not result in increased intracerebral haemorrhage following
      tPA administration. CONCLUSIONS: Patients with acute ischaemic stroke taking
      antithrombotic medications at hospital admission have improved functional
      outcomes. No interaction is noted between use of these medications and outcome
      following thrombolysis. This large prospective cohort study is consistent with
      previous published reports, and supports the notion that pre admission
      antithrombotics may mitigate brain injury during acute stroke.

PMID- 19765120
TI  - The Debrecen Stroke Database: demographic characteristics, risk factors, stroke
      severity and outcome in 8088 consecutive hospitalised patients with acute
      cerebrovascular disease.
AB  - BACKGROUND: High stroke mortality in central-eastern European countries might be
      due to higher stroke incidence, more severe strokes or less effective acute care
      than in countries with lower mortality rate. Hospital databases usually yield
      more detailed information on risk factors, stroke severity and short-term outcome
      than population-based registries. PATIENTS AND METHODS: The Debrecen Stroke
      Database, data of 8088 consecutively hospitalised patients with acute
      cerebrovascular disease in a single stroke centre in East Hungary between October
      1994 and December 2006, is analysed. Risk factors were recorded and stroke
      severity on admission was scored by the Mathew stroke scale. The modified Glasgow
      outcome scale was used to describe patient condition at discharge. RESULTS: Mean
      age was 68+/-13 years, 11.4% had haemorrhagic stroke. The rate of hypertension on
      admission was 79% in men, and 84% in women, 40.3% of men and 19.8% of women were
      smokers, and 34% of all patients had a previous cerebrovascular disease in their
      history. Case fatality was 14.9%, and 43% had some disability at discharge.
      Outcome at discharge was worse with higher age, higher glucose, higher blood
      pressure, higher white cell count and erythrocyte sedimentation rate and more
      severe clinical signs on admission. In multivariate analysis admission blood
      pressure lost its significance in predicting outcome. CONCLUSIONS: In this large
      Hungarian stroke unit database hypertension on admission, smoking and previous
      cerebrovascular disease were more frequent than in most western databases. These
      findings indicate major opportunities for more efficient stroke prevention in
      this and probably other eastern European countries.

PMID- 19765121
TI  - Modelling the burden of stroke in Finland until 2030.
AB  - BACKGROUND: It is well known that increasing age is the strongest risk factor of
      stroke. Therefore, it has been a common belief in many countries including
      Finland that the numbers of stroke patients will increase considerably during the
      next two decades because the population is rapidly ageing. METHODS: The FINMONICA
      and FINSTROKE registers operated in Finland in the Kuopio area and city of Turku
      from 1983 to 1997. The results showed that the incidence, mortality and case
      fatality of stroke declined significantly during that period. Importantly, it was
      established that the trends in incidence and mortality were also declining among
      the elderly (>74 years). We used these results to create a model for the entire
      country. The model was based on the trends present in these registers from Turku
      and Kuopio area and age-specific population projections up to the year 2030 that
      were obtained from Statistics Finland. RESULTS: In the year 2000, the number of
      new first stroke cases was estimated to be 11 500. If the declining trend were to
      level off totally after the year 2000, the number of new strokes would be 20 100
      in the year 2030 due to the ageing of the population. It would be 12 100 if the
      trend continued as favourable as during the years 1983-1997. CONCLUSIONS: Ageing
      of the population will not inevitably increase the burden of stroke in Finland if
      the present declining trends are maintained, but the annual number of cases will
      almost double if the incidence remains at the level of the year 2000.

PMID- 19765122
TI  - Glucose level and brain infarction: a prospective case-control study and
      prospective study.
AB  - BACKGROUND: Hyperglycaemia in the acute phase of stroke has been established as a
      predictor of higher mortality. But recent data regarding active treatment of
      hyperglycaemia showed no clinical benefit suggesting that hyperglycaemia may not
      have a detrimental effect in brain infarction. Additional data are needed to
      resolve this uncertainty and identify patients at higher risk if any. METHODS: A
      total of 477 adult Caucasian patients with brain infarction and 395 age- and sex
      matched controls admitted at the same centres for nonneurological causes were
      recruited consecutively from 12 neurological centres in France.
      Electrocardiographic, carotid ultrasonography, and transcranial Doppler studies
      were performed. Blood was drawn in the morning from fasting subjects for glucose
      measurement. Functional outcome was measured on admission, at 10 days and at 6
      months after the onset of stroke using the modified Rankin scale. RESULTS: Among
      477 brain infarction patients and 395 hospitalised controls the adjusted mean (+/
      SEM) glucose level was higher in cases (6.4+/-1.0 mmol/l) than in controls (6.0+/
      1.01 mmol/l, P=0.006), with a significant heterogeneity across sexes. The fully
      adjusted odds ratio of brain infarction per 1-standard deviation increase in log
      glucose level was 1.02 (95% confidence interval, 0.77-1.37) in men and 2.21 (95%
      confidence interval, 1.44-3.40) in women. Among the 477 brain infarction cases
      elevated admission glucose levels were associated with poor outcomes and higher
      poststroke mortality after adjustment for conventional vascular risk factors and
      infarct volume. These relationships were not modified by sex. CONCLUSIONS:
      Elevated admission glucose levels were associated with brain infarction in women
      only and with a higher 5-year mortality. Further investigation focusing on the
      impact of glucose level in different target population is needed to optimise
      glycaemic management in acute brain infarction patients.

PMID- 19765123
TI  - Better acute treatment induces more investments in chronic care for stroke
      patients.

PMID- 19765124
TI  - The Alberta Stroke Program Early CT Score in clinical practice: what have we
      learned?
AB  - The introduction of brain imaging with computed tomography revolutionised the
      treatment of patients with acute ischaemic stroke. With the visual
      differentiation of haemorrhagic stroke from ischaemic stroke, thrombolytic
      therapy became feasible. The Alberta Stroke Program Early CT Score was devised to
      quantify the extent of early ischaemic changes in the middle cerebral artery
      territory on noncontrast computed tomography. With its systematic approach, the
      score is simple and reliable. However, the assessment of early ischaemic changes
      and Alberta Stroke Program Early CT scoring require training. The Alberta Stroke
      Program Early CT Score is a strong predictor of functional outcome. Furthermore,
      the effectiveness of intraarterial thrombolysis in patients with middle cerebral
      artery occlusion shows effect modification by the Alberta Stroke Program Early CT
      Score. This review summarises the Alberta Stroke Program Early CT Score
      methodology. We illustrate current knowledge regarding Alberta Stroke Program
      Early CT Score applied to clinical trials and comment on how Alberta Stroke
      Program Early CT Score may facilitate clinical treatment decision making and
      future trial design. Moreover, we introduce a modification of the Alberta Stroke
      Program Early CT Score methodology that disregards isolated cortical swelling,
      i.e. focal brain swelling without associated parenchymal hypoattenuation, as
      early ischaemic changes in the Alberta Stroke Program Early CT Score system.

PMID- 19765125
TI  - Intensive care management of acute stroke: general management.
AB  - For a long time, patients with severe stroke were facing therapeutic nihilism of
      the attending physicians. Implementation of do-not-resuscitate-orders may have
      lead to self-fulfilling prophecies and to a pessimistic overestimation of
      prognosis of severe stroke syndromes. However, there have been great advances in
      intensive care management of acute stroke patients and it has been shown that
      treatment on a specialised neurological intensive care unit improves outcome. In
      this review, we will present a summary of the current state-of-the-art intensive
      care management of acute stroke patients. After presenting an overview on general
      management of stroke intensive care patients, special aspects of neurological
      intensive care of acute large middle cerebral artery stroke, intracerebral
      haemorrhage and subarachnoid haemorrhage will be discussed. In part II of the
      review, surgical management options for acute stroke will be discussed in detail.

PMID- 19765126
TI  - Burden of stroke in Indonesia.
AB  - Stroke is the leading cause of death among Indonesians above five years of age,
      comprising 15.4% of all deaths, age-gender-standardised death rate 99/100 000,
      and age-gender-standardised disability-adjusted life years lost 685/100 000.
      Stroke prevalence is 0.0017% in rural Indonesia, 0.022% in urban Indonesia, 0.5%
      among urban Jakarta adults, and 0.8% overall. Frequent risk factors include
      hypertension, smoking and hypercholesterolaemia. The mean age of stroke patients
      is 58.8 years. Subarachnoid haemorrhage is found in 1.4% of patients,
      intracerebral haemorrhage in 18.5%, and ischaemic stroke in 42.9%. Only city
      hospitals have neurology, neurosurgery and neuroimaging services. Indonesia has
      40 stroke units. Commonly used medications for stroke are easily available.
      Hospital-based rehabilitative services are available in large hospitals.
      Traditional medicine is widely practiced. Efforts to combat stroke include
      education, more stroke units and rehabilitative services especially in the rural
      areas.

PMID- 19765127
TI  - The epidemiology of stroke in Pakistan: past, present, and future.
AB  - Stroke is a major public health problem in developing countries of South Asia. In
      this paper, we review the epidemiology of stroke in Pakistan. Most of the
      available data are based on hospital-centred case series addressing established
      stroke risk factors, stroke-related mortality and disability, functional status,
      and case fatality rates. There are limited population-based data regarding the
      prevalence of established stroke risk factors in the general population, and no
      epidemiologic studies have been conducted to specifically identify potential
      stroke risk factors unique to the region. The limited data that are available
      from Pakistan indicate that stroke epidemiology differs between Pakistan and
      Western populations - in Pakistan first stroke occurs at a younger age,
      particularly among women, and there is a higher proportion of haemorrhagic
      strokes. Besides the established stroke risk factors (e.g. hypertension, smoking,
      and diabetes) some potentially unique stroke risk factors related to life style
      and dietary habits such as huqqa smoking, use of dalda and desi ghee, and orally
      consumed forms of tobacco, may exist in Pakistan, and warrant further
      investigation. The shortage of trained stroke epidemiologists is a major limiting
      factor to the conduct of epidemiological stroke studies in Pakistan.
      Epidemiologic data are essential to guide health policy development aimed at
      decreasing the mortality and morbidity from stroke in Pakistan. To facilitate
      this process, medical professionals in Pakistan could participate in the World
      Health Organization's STEPwise approach to stroke surveillance, which provides a
      framework for data collection and comparison between and within populations.

PMID- 19765128
TI  - The burden of paediatric stroke and cerebrovascular disorders in Croatia.
AB  - Pediatric stroke is significantly less common than stroke in adults, but
      represents a major challenge to public health authorities. The aim of this
      retrospective study was to identify the total and annual number of children
      younger than 18 years with arterial ischaemic stroke and transient ischaemic
      attack referred to the Children's Hospital Zagreb, which is a major national
      centre specialised for the treatment and prevention of stroke in children. We
      reviewed the medical records of the Department of Neuropediatrics database at the
      Children's Hospital Zagreb between 1998-2005 in order to provide demographic and
      clinical characteristics and neuroimaging findings in children with arterial
      ischaemic stroke. In the 7-year period, we identified a total of 124 children
      from different geographic areas of Croatia with a confirmed diagnosis of
      transient ischaemic attack (N=77), and arterial ischaemic stroke (N=47).
      Perinatal and childhood arterial ischaemic stroke were equally represented (23
      and 24 children, respectively). The average number of new cases identified each
      year was 18 cases (range: 12-21), seven arterial ischaemic stroke and 11
      transient ischaemic attack cases. Male predominance was found in children with
      arterial ischaemic stroke with a male : female ratio of 1.76 : 1, and was
      slightly higher in childhood arterial ischaemic stroke compared with perinatal
      arterial ischaemic stroke (2 : 1 and 1.56 : 1, respectively). In contrast,
      transient ischaemic attack was more frequently found in girls, and more likely
      identified in older children compared with younger children with arterial
      ischaemic stroke. Obtained data will contribute to better understanding of
      paediatric stroke in Croatia and will provide a base for the establishment of the
      national referral center and national pediatric stroke registry.

PMID- 19765129
TI  - Burden of stroke in Brunei Darussalam.
AB  - Brunei Darussalam, located on the north-west coast of Borneo, has a total area of
      5765 km(2) (1). Divided into four districts - Brunei-Muara, Belait, Temburong and
      Tutong with the majority of the population living in the Brunei-Muara District,
      approximately 74% of the population is urban with an overall population of 390
      000, male/female ratio 1.13 : 1 (2). The main ethnic group is Malay (66.6%),
      which comprises the different Brunei indigenous communities of Malay, Belait,
      Bisaya, Brunei, Dusun, Kedayan, Murut and Tutong. Chinese ethnicity comprises 11%
      while other undefined ethnicities 22.4%. Approximately, 39.2% are aged below 19
      years, 2.8% over 65 years with a median age of 26 years. Brunei's gross national
      income per capita (PPP international dollars) is 49,900 (3).

PMID- 19765130
TI  - The Asymptomatic Carotid Emboli Study: study design and baseline results.
AB  - BACKGROUND: Better methods of identifying which patients with asymptomatic
      carotid stenosis will develop stroke, are required to improve the risk-benefit
      ratio of carotid endarterectomy. A promising method is the detection of
      asymptomatic embolic signals using transcranial Doppler. Embolic signals predict
      stroke risk in symptomatic carotid stenosis, but their predictive role in
      asymptomatic carotid stenosis is uncertain. AIMS: The Asymptomatic Carotid Emboli
      Study is a prospective observational study in patients with asymptomatic carotid
      stenosis> or =70%. METHOD: Two 1-h transcranial Doppler recordings from the
      ipsilateral middle cerebral artery are performed at baseline, and a single-hour
      recording is performed at 6, 12 and 18 months. Follow-up is for 2 years. All
      recordings are centrally blinded to subject identity during analysis. The primary
      hypothesis is: do embolic signals on either of two 1-h recordings at entry
      predict ipsilateral transient ischaemic attack and stroke risk over the following
      2 years? The major secondary hypothesis is: does the presence of embolic signals
      on a single-hour-long recording at baseline or at 6, 12 or 18 months predict
      ipsilateral transient ischaemic attack and stroke risk over the subsequent 6
      month period? RESULTS: Recruitment was completed in October 2007 with 482
      subjects. At the baseline, the proportion of subjects with embolic signals was
      10.7% on recording 1, 10.8% on recording 2 and 16.7% on either of the two
      recordings. Embolic signal prevalence on the two recordings was significantly
      associated (chi(2) 27.48, P<0.0005). Patients without embolic signals were more
      likely to be treated with antiplatelets (90.8 vs 76.9%, P<0.0005) and this
      difference persisted on multivariate analysis. CONCLUSIONS: Asymptomatic Carotid
      Emboli Study will determine whether embolic signal is a useful predictor in
      asymptomatic carotid stenosis, and detection allows its predictive value to be
      compared with clinical features, imaging parameters and ultrasound plaque
      morphology. Baseline data show antiplatelet therapy is associated with fewer
      embolic signals.

PMID- 19765131
TI  - A double-blind, placebo-controlled, randomized trial to evaluate the safety and
      efficacy of Cerebrolysin in patients with acute ischaemic stroke in Asia--CASTA.
AB  - Cerebrolysin has exhibited neuroprotective as well as neurotrophic properties in
      various animal models of cerebral ischaemia and has shown clinical efficacy and
      good safety in several small controlled clinical studies in ischaemic stroke.
      Therefore, a large double-blind placebo-controlled randomized clinical trial was
      launched in Asia to prove the validity of this treatment strategy. In the more
      than 50 participating centres patients with acute ischemic hemispheric stroke are
      randomized within 12 hours of symptoms onset to treatment (30 ml Cerebrolysin
      diluted in physiologic saline) or placebo (saline) given as intravenous infusion
      once daily added to standard care for 10 days. The patients are followed with
      regular visits for 90 days. Efficacy is evaluated on day 90 by three outcome
      scales - modified Rankin Scale, Barthel Index and NIH Stroke Scale - combined to
      single global directional test. Additionally, adverse events are documented to
      prove safety. In this study a total of 1060 patients will be included and
      analysis of data will be completed in 2010. If positive, this trial will add an
      effective strategy to the treatment of acute ischaemic stroke.

PMID- 19765135
TI  - From end time to the time of the end: some reflections about the emergence of
      subjectivity.
AB  - In this article, the author presents the first ten years of the analysis of a
      young patient who just barely escaped an onset of schizophrenia. The patient
      showed defences of the self that had been frozen with regard to his relationship
      to time, and had shut him outside of any rapport with time, forcing him to seek
      as desperately as unconsciously-a 'time of the end', a present time. He explores
      different 'lived times': circular and linear times that are both classical in
      Jungian theory; he then describes what he calls subjective linear 'lived time' as
      a modality for opening up instinctual objectivity to subjectivity's access to the
      symbolic. In his theorization of this passage, he uses the Greek notion of Kairos
      as well as the French psychoanalyst Jean Laplanche's theory of originary
      seduction. Finally, he ties this transition to recent theories in physics of
      complex systems, also called chaos theory, and poses the hypothesis that this
      model can represent two essential qualities of subjectivity: its non
      predictability and its non-reproductability.

PMID- 19765136
TI  - Some limitations of analysis.
AB  - This paper considers some of the difficulties that exist in reconciling the
      'treatment' and the 'cultural' aspects of analytic ideas and practice; the
      extent, for example, to which analysis is both ordinary, and extra-ordinary in
      more than one way. The implications for this for the place of analysis and
      analytical psychotherapy in the mental health services is considered along with
      the ways in which there is a diversity of views about the importance of
      maintaining the presence of analytic ideas and analytic practice in hospitals and
      clinics. Some of the limitations of analysis are discussed where analytic ideas
      and methods move away from their application to patients and patients' material
      into the wider world.

PMID- 19765137
TI  - Going home: migration as enactment and symbol.
AB  - The concepts of home and migration are briefly explored. Reference is made to the
      reflections of several writers on migration suggesting that migrants may
      experience alienation, even permanent melancholia. There is discussion of the
      need to mourn what has been lost and left behind, and of the challenge in
      analytic work with a migrant to relate to the pain of the individual's core self
      amid environmental and cultural losses. The paper outlines the history of an
      individual before her migration from Latin America to London, and tendency to
      idealize as a new arrival. The symbolization process is discussed and it is
      suggested that repetitive enactment in the analytic transference may have been
      needed for her internal reality of estrangement to be confirmed and
      differentiated from her culturally and socially isolated external life as a
      migrant. Only then could she mourn losses and symbolize her inner reality. It is
      suggested that through mourning and symbolization the significance of migration
      for the patient was worked with and transformed so that, following a second
      migration, an ordinary, good enough home could be made in a new place.

PMID- 19765138
TI  - Analytical psychology and Daoist inner alchemy: a response to C.G. Jung's
      'Commentary on The Secret of the Golden Flower'.
AB  - This paper provides a historical, religious-philosophical context for the study
      of the Daoist text known as The Secret of the Golden Flower. An updated study is
      conducted into the controversy over the source of the text including the editions
      translated by Richard Wilhelm and Thomas Cleary. The main teachings of the text
      and the basics of two major denominations of Daoism are introduced to ground
      later critiques of Jung's commentary. The psychodynamics of analytical
      psychology, especially those concerned with integration of unconscious contents
      and the realization of the self (individuation) are compared with the psycho
      spiritual dynamics of integration in Eastern spirituality based on the Golden
      Flower text. The paper concludes that it was amiss for Jung to have equated the
      Western 'unconscious' with states of higher consciousness in Eastern meditation
      practices, although his claim that Eastern higher consciousness is characterized
      by a nebulous state of non-intentionality does raise questions about the
      appropriateness of calling Eastern meditative states 'consciousness'. A new
      concept is required to characterize the special qualities of this psychic state
      shared generally by Eastern spiritual traditions and a more meaningful comparison
      may be found in Jung's concept of the self.

PMID- 19765139
TI  - The cryptomnesic origins of Jung's dream of the multi-storeyed house.
AB  - Jung first recounted his dream of the multi-storeyed house in the 1925 seminars
      to illustrate the concept of the collective unconscious and explain the influence
      of phylogeny on his split with Freud. However, his telling the story of the dream
      belies a cryptomnesic influence of the early writings of psychoanalysis because
      Josef Breuer used a similar image to illustrate the structure of the psyche which
      Edouard Claparede associated with a phylogenetic inheritance. When telling the
      story of the dream, Jung misrepresented Freud's position, creating the impression
      of there being a bigger difference between their theories than was actually the
      case, and giving the dream a fictional significance for the breakdown of their
      relationship. In fact, Jung followed Freud into the fields of mythology and
      phylogenetics, and their split was due primarily to their different attitudes
      towards sexuality rather than phylogeny. The dream image has therefore led to a
      misunderstanding of Freudian theory when viewed from within a Jungian
      perspective. Freud believed there was a phylogenetic layer in the psyche, though
      he held a different view to Jung on its nature and importance.

PMID- 19765159
TI  - Towards consensus on how to measure neutral genetic diversity?

PMID- 19765160
TI  - Genealogical analyses in open populations: the case of three Arab-derived Spanish
      horse breeds.
AB  - This research assesses the genetic composition of three Arab-derived Spanish
      horse breeds as an example to highlight the major shortcomings related to
      genealogical analyses in open populations and to propose approaches useful to
      deal with this task. The studbooks of three Spanish Arab (SA)-derived horse
      breeds, Spanish Anglo-Arab (dAA), Hispano-Arab (dHA) and Spanish Sport Horse
      (dSSH) and those of their parental breeds SA, Spanish Purebred (SPB) and
      Thoroughbred (TB), totalling 211 754 individuals, were available. The genealogies
      of the dAA, dHA and dSSH were analysed not only using the corresponding studbook
      (breed exclusive dataset) but also including the genealogies of the founders from
      parental breeds (completed dataset). Coancestry analyses revealed that the
      present SA-derived populations share more genes with the Arab than with the other
      parental breeds. Effective population size was computed by accounting for
      migration rates to obtain an equivalent closed-population effective size
      ((eq)N(e)) of 39.2 for the dAA, 56.3 for dHA and 114.1 for dSSH. The essayed
      methodologies were useful for characterising populations involving migration. The
      consequences of the management of the analysed breeds are discussed. The results
      emphasize the need to include the complete genealogies of the individuals to
      attain reliable genealogical parameters.

PMID- 19765161
TI  - Pedigree analysis in the Austrian Noriker draught horse: genetic diversity and
      the impact of breeding for coat colour on population structure.
AB  - The pedigree of the current Austrian Noriker draught horse population comprising
      2808 horses was traced back to the animals considered as founders of this breed.
      In total, the number of founders was 1991, the maximum pedigree length was 31
      generations, with an average of 12.3 complete generations. Population structure
      in this autochthonous Austrian draught horse breed is defined by seven breeding
      regions (Carinthia, Lower Austria, Salzburg, Styria, Tyrol, Upper Austria and
      Vorarlberg) or through six coat colour groups (Bay, Black, Chestnut, Roan,
      Leopard, Tobiano). Average inbreeding coefficients within the breeding regions
      ranged from 4.5% to 5.5%; for the colour groups, the coefficients varied from
      3.5% to 5.9%. Other measures of genetic variability like the effective number of
      founders, ancestors and founder genomes revealed a slightly different genetic
      background of the subpopulations. Average co-ancestries between and within
      breeding areas showed that the Salzburg population may be considered as the
      nucleus or original stock whereas all other subpopulations showed high
      relationship to horses from Salzburg. The target of draught horse breeding in the
      21st century does not meet the breeding concept of maximizing genetic gains any
      more. Stabilizing selection takes place. In this study, we show that demographic
      factors as well as structure given by different coat colours helped to maintain
      genetic diversity in this endangered horse breed.

PMID- 19765162
TI  - Inbreeding trends and pedigree analysis of Bavarian mountain hounds, Hanoverian
      hounds and Tyrolean hounds.
AB  - The objective of this study was to analyse genetic diversity for the three scent
      hound breeds Bavarian mountain hound (BMH), Hanoverian hound (HH) and Tyrolean
      hound (TH) using all available pedigree information from scent-hound kennel clubs
      for these three breeds throughout Europe. The pedigree data of the BMH and the HH
      date back to 1912 and 1894, respectively. Pedigree data of the TH were available
      from the 1960s onwards. The reference populations included all BMH (n = 3231), HH
      (n = 1371) and TH (n = 1167) dogs registered between 1992 and 2004. Average
      generation intervals were 5.3 years for the BMH and 5.0 years for the HH and TH.
      Average inbreeding coefficients for the reference populations were 4.5%, 6.8% and
      9.5% for the BMH, HH and TH. The effective numbers of founders, ancestors and
      founder genomes were lowest for the TH and highest for the BMH. The effective
      numbers of founder genomes were 10.9, 5.6 and 4.3 for the BMH, HH and TH.
      Effective population size was largest for the BMH with 72.7 effective breeding
      animals, followed by the HH with 50.9 and TH with 26.5. The most important ten
      ancestors had genetic contributions to the reference populations of 54.4%, 65.2%
      and 77.9% in the BMH, HH and TH. The results of our study indicate the need for
      careful breed management in these highly specialized hound breeds to maintain
      genetic diversity. European stud books should be established for these dog breeds
      in order to avoid inbreeding due to missing pedigree records.

PMID- 19765163
TI  - Accessing genotype by environment interaction using within- and across-country
      test-day random regression sire models.
AB  - First-lactation test-day (TD) milk records of Luxembourg and Tunisian Holsteins
      were analysed for evidence of genotype by environment interaction (G x E). The
      joint data included 730 810 TD records of 87 734 cows and 231 common sires.
      Random regression TD sire models with fourth-order Legendre polynomials were used
      to estimate genetic parameters via within- and across-country analyses. Daily
      heritability estimates of milk yield from within-country analysis were between
      0.11 and 0.32, and 0.03 and 0.13 in Luxembourg and Tunisia, respectively.
      Heritability estimates for 305-day milk yield and persistency (defined as the
      breeding value for milk yield on DIM 280 minus the breeding value on DIM 80) were
      lower for Tunisian Holsteins compared with the Luxembourg population.
      Specifically, heritability for 305-day milk yield was 0.16 for within- and 0.11
      for across-country analyses for Tunisian Holsteins and 0.38 for within- and 0.40
      for across-country analyses for Luxembourg Holsteins. Heritability for apparent
      persistency was 0.02 for both within- and across-country analyses for Tunisian
      Holsteins and 0.08 for within- and 0.09 for across-country analyses for
      Luxembourg Holsteins. Genetic correlations between the two countries were 0.50
      for 305-day milk yield and 0.43 for apparent persistency. Moreover, rank
      correlations between the estimated breeding values of common sires for 305-day
      milk yield and persistency, estimated separately in each country, were low. Low
      genetic correlations are evidence for G x E for milk yield production while low
      rank correlations suggest different rankings of sires in both environments.
      Results from this study indicate that milk production of daughters of the same
      sires depends greatly on the production environment and that importing high merit
      semen for limited input systems might not be an effective strategy to improve
      milk production.

PMID- 19765164
TI  - Multi-trait animal model estimation of genetic parameters for linear type and
      gait traits in the Belgian warmblood horse.
AB  - Genetic parameters for the height at withers, 27 linear type and six linear gait
      traits were estimated for the Belgian warmblood horse. Observations on 987 mares,
      mostly 3 years old, were analysed using a multi-trait animal model. The
      statistical model included appraiser, age and location (date x place of
      appraisal) as fixed effects. Genetic parameters were estimated using a canonical
      transformation and an expectation-maximization restricted maximum likelihood
      algorithm with an additional deceleration step. Estimates of heritability for the
      33 linear traits were between 0.15 and 0.55. Heritability of the height at
      withers was 0.34 +/- 0.06. Estimated genetic correlations ranged from -0.60 to
      0.98 with an average SE of 0.10. The highest positive correlations were found
      among traits of walk and among traits of trot. Volume and the quality of legs
      were the most negatively correlated. Estimated genetic parameters indicated that
      the linear scoring system is a valuable tool to assess conformation. The full
      (co)variance matrix is now available for breeding value estimation to support
      selection for conformation and gaits.

PMID- 19765165
TI  - Genetic associations between age at first calving and heifer body weight and
      scrotal circumference in Nelore cattle.
AB  - Summary Age at first calving (AFC) measures the entry of heifers into the beef
      cattle production system. This trait can be used as a selection criterion for
      earlier reproductive performance. Using data from Nelore cattle participating in
      the 'Program for Genetic Improvement of the Nelore Breed' (PMGRN-Nelore Brazil),
      bi-trait analyses were performed using the restricted maximum likelihood method,
      based on an AFC animal model and the following traits: female body weight
      adjusted to 365 (BW365) and 450 (BW450) days of age, and male scrotal
      circumference adjusted to 365 (SC365), 450 (SC450), 550 (SC550) and 730 (SC730)
      days of age. The heritability estimates for AFC ranged from 0.02 +/- 0.02 to 0.04
      +/- 0.02. The estimates of additive direct heritabilities (with standard error)
      for BW365, BW450, SC365, SC450, SC550 and SC730 were 0.36 +/- 0.07, 0.38 +/-
      0.07, 0.48 +/- 0.07, 0.65 +/- 0.07, 0.64 +/- 0.07 and 0.42 +/- 0.07,
      respectively, and the genetic correlations with AFC were -0.38, -0.33, 0.10, 
      0.13, -0.13 and 0.06, respectively. In the herds studied, selection for SC365,
      SC450, SC550 or SC730 should not cause genetic changes in AFC. Selection based on
      BW365 or BW450 would favor smaller AFC breeding values. However, the low
      magnitude of direct heritability estimates for AFC in these farms indicates that
      changes in phenotypical expression depend mostly on non-genetic factors.

PMID- 19765166
TI  - Stearoyl-CoA desaturase 1 3'UTR SNPs and their influence on milk fatty acid
      composition of Canadian Holstein cows.
AB  - Stearoyl-CoA desaturase 1 (SCD1) catalyses the synthesis of conjugated linoleic
      acid (CLA) and mono-unsaturated fatty acids (MUFA) in the mammary gland of
      ruminant animals. Considerable variations in CLA and MUFA have been reported
      among animals of the same contemporary group. We hypothesized that single
      nucleotide polymorphisms (SNPs) in the 5' and 3' untranslated regions (UTRs) of
      the SCD1 gene would influence the production of SCD1 enzyme and consequently its
      activity in the mammary gland, which may account for some of the observed within
      breed variations in CLA and MUFA. The 5' and 3'UTRs of the SCD1 gene of 46
      Holsteins and 35 Jerseys were analysed for SNPs by sequencing. No SNPs were
      identified in the 5'UTR, while 14 SNPs were identified in the 3'UTR region.
      Further analysis revealed three haplotype structures or regulatory variants in
      Holsteins: named H1, H2 and H3 and only H1 and H3 in Jerseys. An IRES motif was
      found in the H1 variant. A subsequent association study involving the milk fatty
      acid profiles of 862 Holstein cows found the H1 regulatory variant to be
      associated with higher C10 and C12 desaturase indices and consequently with
      higher contents of C10:1 and C12:1 relative to the H3 variant. The effects of the
      H2 variant were intermediate to those of H1 and H3. SNPs in the 3'UTR of the SCD1
      gene could therefore explain some of the within-breed variations in MUFA content
      of milk fat.

PMID- 19765167
TI  - Analysis of the mouse high-growth region in pigs.
AB  - In the mouse, homozygous animals for the high growth mutation show a 30-50%
      increase in growth without becoming obese. This region is homologous to the
      distal part of pig chromosome 5 (SSC5). A previous genome scan detected several
      quantitative trait loci (QTL) in this region for body composition and meat
      quality using a three generation Berkshire x Yorkshire resource family. In this
      study, the effects on swine growth, fat and meat quality traits of three genes
      previously identified within the mouse high growth region were analysed. The
      genes studied were CASP2 and RIPKI domain containing adaptor with death domain
      (CRADD), suppressor of cytokine signalling 2 (SOCS2) and plexinC1 (PLXNC1). In
      addition, the influence of two other genes located very close to this region,
      namely the plasma membrane calcium-transporting ATPase 1 (ATP2B1) and dual
      specificity phosphatase 6 (DUSP6) genes, was also investigated. Single nucleotide
      polymorphisms were identified and used to map these genes to the QTL region on
      SSC5. Results indicate significant associations between these genes and several
      phenotypic traits, including fat deposition and growth in pigs. The present study
      suggests associations of these genes with swine fat and growth related traits,
      but further studies are needed in order to clearly identify the genes involved in
      the regulation of the QTL located on SSC5.

PMID- 19765168
TI  - Aortic valve replacement in noncompaction cardiomyopathy at two-year follow-up.
AB  - We report a male patient suffering left ventricular noncompaction cardiomyopathy
      in combination with low-gradient aortic stenosis. Preoperative echocardiography
      and magnetic resonance imaging revealed the diagnosis. After aortic valve
      replacement, the clinical course was uneventful. Two years of follow-up confirmed
      that the general prognosis was primarily affected by impaired ventricular
      function, thrombembolism, and arrhythmias.

PMID- 19765169
TI  - Complete vacuum-assisted sternal closure following neonatal cardiac surgery.
AB  - Vacuum-assisted closure (VAC) has been used with success in the management of
      adults and children with sternal infections. However, this technique has not been
      applied previously to neonates requiring delayed sternal closure as the sole
      modality of therapy. In this article, we describe the management of two newborns
      with hypoplastic left heart syndrome in whom complete sternal wound healing was
      accomplished solely by using the VAC system. The implications of this new
      modality of treatment are discussed.

PMID- 19765170
TI  - Anti-CD44 induces apoptosis in T lymphoma via mitochondrial depolarization.
AB  - A blockade of CD44 can interfere with haematopoietic and leukemic stem cell
      homing, the latter being considered as a therapeutic option in haematological
      malignancies. We here aimed to explore the molecular mechanism underlying the
      therapeutic efficacy of anti-CD44. We noted that in irradiated mice reconstituted
      with a bone marrow cell transplant, anti-CD44 exerts a stronger effect on
      haematopoietic reconstitution than on T lymphoma (EL4) growth. Nonetheless, in
      the non-reconstituted mouse anti-CD44 suffices for a prolonged survival of EL4
      bearing mice, where anti-CD44-prohibited homing actively drives EL4 cells into
      apoptosis. In vitro, a CD44 occupancy results in a 2-4-fold increase in apoptotic
      EL4 cells. Death receptor expression (CD95, TRAIL, TNFRI) remains unaltered and
      CD95 cross-linking-mediated apoptosis is not affected. Instead, CD44 ligation
      promotes mitochondrial depolarization that is accompanied by caspase-9 cleavage
      and is inhibited in the presence of a caspase-9 inhibitor. Apoptosis becomes
      initiated by activation of CD44-associated phosphatase 2A (PP2A) and proceeds via
      ERK1/2 dephosphorylation without ERK1/2 degradation. Accordingly, CD44-induced
      apoptosis could be mimicked by ERK1/2 inhibition, that also promotes EL4 cell
      apoptosis through the mitochondrial pathway. Thus, during haematopoietic stem
      cell reconstitution care should be taken not to interfere by a blockade of CD44
      with haematopoiesis, which could be circumvented by selectively targeting
      leukemic CD44 isoforms. Beyond homing/settlement in the bone marrow niche, anti
      CD44 drives leukemic T cells into apoptosis via the mitochondrial death pathway
      by CD44 associating with PP2A. Uncovering this new pathway of CD44-induced
      leukemic cell death provides new options of therapeutic interference.

PMID- 19765171
TI  - Bone marrow derived cells in the tumour microenvironment contain cells with
      primitive haematopoietic phenotype.
AB  - Infiltration of bone marrow derived cells is part of the angiogenic switch
      required for uncontrolled tumour growth. However, the nature of the tumour
      infiltrating cells from bone marrow has not been fully elucidated. To investigate
      the phenotype of bone marrow derived cells within a tumour, we employed the Lewis
      lung carcinoma (LLC) murine tumour model. We followed bone marrow derivation of
      tumour-infiltrating cells through transplantation of CD45.2 bone marrow cells
      into pre-irradiated CD45.1 mice. We found robust CD45.2 donor type chimerism in
      bone marrow and blood of CD45.1 recipient tumour-bearing mice. Flow cytometric
      analysis of LLC tumours showed, in addition to previously described pro
      angiogenic CD45(+)VEGFR2(+)'endothelial progenitor cells' (EPC), or
      CD45(+)Tie2(+)'Tie2-expressing monocytes' (TEM), incorporation of donor type
      lineage marker negative (Lin(-)) and Lin(-)Sca1(+) undifferentiated
      haematopoietic cell types. Immunohistochemical analysis confirmed the extravasal
      location of the primitive haematopoietic cells. Flow-cytometric sorting of bone
      marrow cells and subsequent analysis in haematopoietic colony-forming assays
      revealed that cells with a Lin(-)Sca1(+) phenotype, which were initially negative
      for VEGFR2 and Tie2, gave rise to VEGFR2(+) and/or Tie2(+) cells. Moreover, Lin(
      ) bone marrow cells pre-labelled with the membrane dye PKH26 (a red fluorochrome)
      and transplanted i.v. into tumour-bearing mice were found to extravasate and
      incorporate into LLC tumours within 24 hrs. Thus, primitive haematopoietic
      precursors which are thought to be precursors of EPC and TEMs, constitute a part
      of the tumour microenvironment. This makes them an attractive target cell
      population for tumour-directed cellular therapies.

PMID- 19765172
TI  - The cellular component of the mucinous nevus consists of CD34-positive
      fibroblasts.

PMID- 19765173
TI  - The histopathologic spectrum of regression in atypical fibroxanthoma.
AB  - BACKGROUND: Atypical fibroxanthoma (AFX) with prominent fibrosis, sclerosis and
      hyalinization, and near-total tumor regression is rare. METHODS: Eight cases of
      AFX presenting with fibrosis were reviewed as to their tumor architecture, the
      degree and pattern of fibrosis and the associated inflammatory cell infiltrate.
      RESULTS: Seven of eight cases had an exophytic architecture, with ulceration in
      one case. The degree of fibrosis ranged from 10% to 90%. Early fibrosis (2/8
      cases) occurred as thickened sclerotic collagen bundles, either dispersed between
      the neoplastic cells or as septa imparting a multilobular appearance. Advanced
      fibrosis (6/8 cases) was associated with lamellar sclerosis, keloidal features,
      hyalinization and with near-total tumor replacement. Prominent fibrosis rimming
      the periphery was present in all tumors. An associated lymphoid cell infiltrate
      with plasma cells and occasionally eosinophils was observed. CONCLUSIONS:
      Fibrosis with prominent sclerosis and hyalinization replacing the tumor is rare
      in AFX. Advanced fibrosis, in the absence of a history of prior trauma or
      surgery, may indicate spontaneous regression. These cases emphasize the
      importance of recognizing this subset of AFX in order to avoid misinterpretation,
      particularly in cases with few residual atypical cells.

PMID- 19765174
TI  - Drosophila melanogaster males respond differently at the behavioural and genome
      wide levels to Drosophila melanogaster and Drosophila simulans females.
AB  - Drosophila melanogaster are found in sympatry with Drosophila simulans, and
      matings between the species produce nonfertile hybrid offspring at low frequency.
      Evolutionary theory predicts that females choose mates, so males should alter
      their behaviour in response to female cues. We show that D. melanogaster males
      quickly decrease courtship towards D. simulans females. Courtship levels are
      reduced within 5 min of exposure to a heterospecific female, and overall
      courtship is significantly lower than courtship towards conspecific females. To
      understand changes at the molecular level during mate choice, we performed
      microarray analysis on D. melanogaster males that courted heterospecific D.
      simulans females and found nine genes have altered expression compared with
      controls. In contrast, males that court conspecific females alter expression of
      at least 35 loci. The changes elicited by conspecific courtship likely modulate
      nervous system function to reinforce positive conspecific signals and dampen the
      response to heterospecific signals.

PMID- 19765175
TI  - Evidence for autotetraploidy associated with reproductive isolation in
      Saccharomyces cerevisiae: towards a new domesticated species.
AB  - Partial or whole-genome duplications have played a major role in the evolution of
      new species. We have investigated the variation of ploidy level in a panel of
      domesticated strains of Saccharomyces cerevisiae coming from different
      geographical origins. Segregation studies and crosses with tester strains of
      different ploidy levels showed that part of the strains were well-balanced
      autotetraploids displaying tetrasomic inheritance. The presence of up to four
      different alleles for various loci is consistent with a polyploidization
      mechanism relying on the fusion of two nonreduced meiospores coming from two S.
      cerevisiae strains. Autotetraploidy was also in accordance with karyotype and
      flow cytometry analyses. Interestingly, most bakery strains were tetraploids,
      suggesting a link between ploidy level and human use. The null or drastically
      reduced fertility of the hybrids between tetraploid and diploid strains indicated
      that domesticated S. cerevisiae strains are composed of two groups isolated by
      post-zygotic reproductive barriers.

PMID- 19765176
TI  - Regenerative medicine: a 2009 overview.
AB  - The rapidly evolving field of regenerative medicine holds much promise for cell
      based therapies for a range of debilitating conditions from spinal cord injury to
      haematological and neurological diseases. The groundbreaking discovery of induced
      pluripotent stem (iPS) cells has offered new perspectives on disease progression
      and the possibility of patient-specific cell transplants. In this review we first
      give a brief history of the field of regenerative medicine and then discuss the
      current state of regenerative medicine with a focus on embryonic stem cells and
      iPS cells. In order to keep abreast with this rapidly developing field, the
      Journal of Internal Medicine organized a 2-day Symposium, on March 12-13(th)
      2009, at the Karolinska Insitute in Stockholm, which featured talks by 19 leading
      scientists in the field of regenerative medicine. In this review, we discuss the
      Symposium and introduce six accompanying review articles, by Symposium speakers,
      which focus on some of the topics discussed at the meeting.

PMID- 19765177
TI  - New light on the biology and developmental potential of haematopoietic stem cells
      and progenitor cells.
AB  - Even though stem cells have been identified in several tissues, one of the best
      understood somatic stem cells is the bone marrow residing haematopoietic stem
      cell (HSC). These cells are able to generate all types of blood cells found in
      the periphery over the lifetime of an animal, making them one of the most
      profound examples of tissue-restricted stem cells. HSC therapy also represents
      one of the absolutely most successful cell-based therapies applied both in the
      treatment of haematological disorders and cancer. However, to fully explore the
      clinical potential of HSCs we need to understand the molecular regulation of cell
      maturation and lineage commitment. The extensive research effort invested in this
      area has resulted in a rapid development of the understanding of the relationship
      between different blood cell lineages and increased understanding for how a
      balanced composition of blood cells can be generated. In this review, several of
      the basic features of HSCs, as well as their multipotent and lineage-restricted
      offspring, are addressed, providing a current view of the haematopoietic
      development tree. Some of the basic mechanisms believed to be involved in lineage
      restriction events including activities of permissive and instructive external
      signals are also discussed, besides transcription factor networks and epigenetic
      alterations to provide an up-to-date view of early haematopoiesis.

PMID- 19765178
TI  - Cellular origins of beta-cell regeneration: a legacy view of historical
      controversies.
AB  - Beta-cell regeneration represents a major goal of therapy for diabetes.
      Unravelling the origin of beta cells during pancreatic regeneration could help
      restore a functional beta-cell mass in diabetes patients. This scientific
      question has represented a longstanding interest still intensively investigated
      today. This review focuses on pioneering observations and subsequent theories
      made 100 years ago and describes how technical innovation helped resolve some,
      but not all, of the controversies generated by these early investigators. At the
      end of the 19th century, complete pancreatectomy demonstrated the crucial
      physiological role of the pancreas and its link with diabetes. Pancreatic injury
      models, including pancreatectomy and ductal ligation, allowed investigators to
      describe islet function and to assess the regenerative capacity of the pancreas.
      Three main theories were proposed to explain the origins of newly formed islets:
      (i) transdifferentiation of acinar cells into islets, (ii) islet neogenesis, a
      process reminiscent of islet formation during embryonic development, and (iii)
      replication of preexisting islet cells. Despite considerable technical innovation
      in the last 50 years, the origin of new adult beta cells remains highly
      controversial and the same three theories are still debated today.

PMID- 19765179
TI  - Human hepatocyte transplantation: state of the art.
AB  - Hepatocyte transplantation is making its transition from bench to bedside for
      liver-based metabolic disorders and acute liver failure. Over eighty patients
      have now been transplanted world wide and the safety of the procedure together
      with medium-term success has been established. A major limiting factor in the
      field is the availability of good quality cells as hepatocytes are derived from
      grafts that are deemed unsuitable for transplantation. Alternative sources of
      cell, including stem cells may provide a sustainable equivalent to primary
      hepatocytes. There is also a need to develop techniques that will improve the
      engraftment, survival and function of transplanted hepatocytes. Such developments
      may allow hepatocyte transplantation to become an accepted and practical
      alternative to liver transplantation in the near future.

PMID- 19765180
TI  - Neuronal cell replacement in Parkinson's disease.
AB  - Transplantation of foetal dopamine neurons into the striatum of Parkinson's
      disease patients can provide restoration of the dopamine system and alleviate
      motor deficits. However, cellular replacement is associated with several
      problems. As with pharmacological treatments, cell therapy can lead to disabling
      abnormal involuntary movements (dyskinesias). The exclusion of serotonin and GABA
      neurons, and enrichment of substantia nigra (A9) dopamine neurons, may circumvent
      this problem. Furthermore, although grafted foetal dopamine neurons can survive
      in Parkinson's patients for more than a decade, the occurrence of Lewy bodies
      within such transplanted cells and reduced dopamine transporter and tyrosine
      hydroxylase expression levels indicate that grafted cells are associated with
      pathology. It will be important to understand if such abnormalities are host- or
      graft induced and to develop methods to ensure survival of functional dopamine
      neurons. Careful preparation of cellular suspensions to minimize graft-induced
      inflammatory responses might influence the longevity of transplanted cells.
      Finally, a number of practical and ethical issues are associated with the use of
      foetal tissue sources. Thus, future cell therapy is aiming towards the use of
      embryonic stem cell or induced pluripotent stem cell derived dopamine neurons.

PMID- 19765181
TI  - Skeletal muscle stem cells in developmental versus regenerative myogenesis.
AB  - Tissue and organ regeneration proceed in a coordinated manner to restore proper
      function after trauma. Vertebrate skeletal muscle has a remarkable ability to
      regenerate after repeated and complete destruction of the tissue, yet limited
      information is available on how muscle stem and progenitor cells, and other
      nonmuscle cells, reestablish homeostasis after the regenerative process. The
      genetic pathways that regulate the establishment of skeletal muscle in the embryo
      have been studied extensively, and many of the genes that govern muscle stem cell
      maintenance and commitment are redeployed during adult homeostasis and
      regeneration. Therefore, correlates can be made between embryonic muscle
      development and postnatal regeneration. However, there are some important
      distinctions between prenatal development and regeneration - in the context of
      the cells, niche, anatomy and the regulatory genes employed. The similarities and
      distinctions between these two scenarios are the focus of this review.

PMID- 19765182
TI  - Mesenchymal stem cells and cartilage in situ regeneration.
AB  - Cartilage repair is a very successful pioneering area of regenerative medicine in
      which techniques of in situ regeneration and cell and tissue transplantation
      dominate over cell-free approaches to generate durable neocartilage. This review
      concentrates on advantages and limitations of mesenchymal stem cell (MSC)-based
      cartilage repair strategies induced by marrow stimulation. Detailed knowledge on
      the biology of MSC will be discussed in light of the requirements for MSC
      recruitment, retention, proliferation and chondrogenic differentiation. An
      improved microenvironment with timely correlated signals from biomaterials,
      growth factors, proteases, adjacent cartilage and subchondral bone may be key to
      a third generation of techniques to regenerate hyaline cartilage.

PMID- 19765183
TI  - Chronic kidney disease: a new opportunity for better cardiovascular risk
      stratification.

PMID- 19765185
TI  - TDP-43 is recruited to stress granules in conditions of oxidative insult.
AB  - Transactive response DNA-binding protein 43 (TDP-43) forms abnormal ubiquitinated
      and phosphorylated inclusions in brain tissues from patients with amyotrophic
      lateral sclerosis (ALS) and frontotemporal lobar degeneration. TDP-43 is a
      DNA/RNA-binding protein involved in RNA processing, such as transcription, pre
      mRNA splicing, mRNA stabilization and transport to dendrites. We found that in
      response to oxidative stress and to environmental insults of different types TDP
      43 is capable to assemble into stress granules (SGs), ribonucleoprotein complexes
      where protein synthesis is temporarily arrested. We demonstrated that a specific
      aminoacidic interval (216-315) in the C-terminal region and the RNA-recognition
      motif 1 domain are both implicated in TDP-43 participation in SGs as their
      deletion prevented the recruitment of TDP-43 into SGs. Our data show that TDP-43
      is a specific component of SGs and not of processing bodies, although we proved
      that TDP-43 is not necessary for SG formation, and its gene silencing does not
      impair cell survival during stress. The analysis of spinal cord tissue from ALS
      patients showed that SG markers are not entrapped in TDP-43 pathological
      inclusions. Although SGs were not evident in ALS brains, we speculate that an
      altered control of mRNA translation in stressful conditions may trigger motor
      neuron degeneration at early stages of the disease.

PMID- 19765184
TI  - The molecular physiology of activity-dependent bulk endocytosis of synaptic
      vesicles.
AB  - Central nerve terminals release neurotransmitter in response to a wide variety of
      stimuli. Because maintenance of neurotransmitter release is dependent on the
      continual supply of synaptic vesicles (SVs), nerve terminals possess an array of
      endocytosis modes to retrieve and recycle SV membrane and proteins. During mild
      stimulation conditions, single SV retrieval modes such as clathrin-mediated
      endocytosis predominate. However, during increased neuronal activity, additional
      SV retrieval capacity is required, which is provided by activity-dependent bulk
      endocytosis (ADBE). ADBE is the dominant SV retrieval mechanism during elevated
      neuronal activity. It is a high capacity SV retrieval mode that is immediately
      triggered during such stimulation conditions. This review will summarize the
      current knowledge regarding the molecular mechanism of ADBE, including molecules
      required for its triggering and subsequent steps, including SV budding from bulk
      endosomes. The molecular relationship between ADBE and the SV reserve pool will
      also be discussed. It is becoming clear that an understanding of the molecular
      physiology of ADBE will be of critical importance in attempts to modulate both
      normal and abnormal synaptic function during intense neuronal activity.

PMID- 19765186
TI  - Identification of novel spartin-interactors shows spartin is a multifunctional
      protein.
AB  - Hereditary spastic paraplegia describes a group of neurodegenerative diseases
      characterized by lower limb progressive weakness and spasticity. Troyer syndrome
      is an autosomal recessive form of hereditary spastic paraplegia caused by a
      frameshift mutation (1110delA) in the SPG20 gene encoding spartin protein, the
      cellular function of which remains unknown. Knowledge about spartin-interactors
      is also very limited. In this study, we apply a broad spectrum of proteomics
      techniques to identify novel spartin-binding proteins. We used a Tandem Affinity
      Purification technique followed by HPLC-mass spectrometry to characterize
      potential spartin-binding partners. Selected putative interactions were confirmed
      by co-immunoprecipitation experiments. We identified 94 potential spartin-binding
      proteins which were grouped into functional categories. We performed co
      immunoprecipitation experiments to confirm that spartin interacts with GRP78,
      GRP75 and nucleolin proteins. Additionally, our mass spectrometry results
      confirmed previously published information about spartin interaction with
      ubiquitin and the E3 ubiquitin-protein ligases, AIP4/Itch and AIP5/WWP1. Our
      studies suggest that spartin is a multifunctional protein and for the first time
      we suggest a role for spartin in protein folding and turnover both in
      mitochondria and endoplasmic reticulum. We also show for the first time
      interaction between spartin and a nucleolar protein, nucleolin.

PMID- 19765187
TI  - Neuroprotective effect of L-dopa on dopaminergic neurons is comparable to
      pramipexol in MPTP-treated animal model of Parkinson's disease: a direct
      comparison study.
AB  - Parkinson's disease (PD) is a chronic neurodegenerative disease characterized by
      selective loss of dopaminergic neurons in the pars compacta of the substantia
      nigra. Levodopa (l-dopa) and dopamine agonists have been most commonly used for
      symptomatic treatment. However, there are discrepancies between clinical and
      experimental data with respect to the neuroprotective effects of these drugs on
      dopaminergic neurons. In this study, to determine whether L-dopa is toxic or
      dopamine agonist is neuroprotective to dopaminergic neurons, we evaluated the
      neuroprotective properties of l-dopa and the pramipexol (PPX), one of dopamine
      agonists, with a focus on the regulatory effects of the anti-oxidant properties
      and cell survival or apoptotic signal pathways in the same experimental design,
      using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated PD animals. The
      glutathione level in MPTP-treated mice was significantly increased by PPX
      administration but not by L-dopa treatment. The expression of phosphorylated
      extracellular signal regulated kinase in MPTP-treated mice was significantly
      increased only with L-dopa treatment. Treatment with either l-dopa or PPX in MPTP
      treated mice led to significantly decreased expressions of JNK phosphorylation,
      Bax, and cytochrome c and to an increased level of Bcl-2 expression with a
      similar degree, compared with the levels in MPTP-only treated mice.
      Immunohistochemical analysis showed that both L-dopa and PPX increased
      significantly survival of dopaminergic neurons in MPTP-treated mice. Our study
      demonstrated that both l-dopa and PPX had comparable neuroprotective properties
      for dopaminergic neurons in MPTP-treated PD animal models, through modulation of
      cell survival and apoptotic pathways.

PMID- 19765188
TI  - Mechanism of abnormal growth in astrocytes derived from a mouse model of GM2
      gangliosidosis.
AB  - Sandhoff disease is a progressive neurodegenerative disorder caused by mutations
      in the HEXB gene which encodes the beta-subunit of N-acetyl-beta-hexosaminidase A
      and B, resulting in the accumulation of the ganglioside GM2. We isolated
      astrocytes from the neonatal brain of Sandhoff disease model mice in which the N
      acetyl-beta-hexosaminidase beta-subunit gene is genetically disrupted (ASD).
      Glycolipid profiles revealed that GM2/GA2 accumulated in the lysosomes and not on
      the cell surface of ASD astrocytes. In addition, GM3 was increased on the cell
      surface. We found remarkable differences in the cell proliferation of ASD
      astrocytes when compared with cells isolated from wild-type mice, with a faster
      growth rate of ASD cells. In addition, we observed increased extracellular,
      signal-regulated kinase (ERK) phosphorylation in ASD cells, but Akt
      phosphorylation was decreased. Furthermore, the phosphorylation of ERK in ASD
      cells was not dependent upon extracellular growth factors. Treatment of ASD
      astrocytes with recombinant N-acetyl-beta-hexosaminidase A resulted in a decrease
      of their growth rate and ERK phosphorylation. These results indicated that the up
      regulation of ERK phosphorylation and the increase in proliferation of ASD
      astrocytes were dependent upon GM2/GA2 accumulation. These findings may represent
      a mechanism in linking the nerve cell death and reactive gliosis observed in
      Sandhoff disease.

PMID- 19765189
TI  - Broad DNA repair responses in neural injury are associated with activation of the
      IL-6 pathway in cholesterol-fed rabbits.
AB  - The importance of DNA repair in the pathogenic mechanism of Alzheimer's Disease
      (AD) is still poorly understood. Here, we report that a broad range of responses
      by DNA repair proteins plays a critical role in the regulation of inflammatory
      response in rabbits fed with cholesterol-rich diet, a model system for AD. We
      found accumulation of oxodG DNA adduct in the brain of rabbits fed with
      cholesterol-enriched diets compared to control diets, which subsequently induced
      a broad range of DNA repair protein activities. Also, the hippocampus was
      identified as the primary site of oxidative DNA damage and elevated OGG1
      activity. In addition, a physical interaction between XPB and OGG1 may account
      for a potential mechanism involving these DNA repair responses. DNA repair
      proteins also impact activation of various signaling cascades, including Src in
      response to cholesterol oxidation. Furthermore, OGG1 deficient mice showed no IL
      6 activation as seen in wt mice but a drastic increase of TNF-alpha, a pro
      inflammatory cytokine. Thus, OGG1 may be associated with cytokine production
      induced by high cholesterol levels, impacting neurodegeneration. Together, our
      studies suggest that critical DNA repair proteins are associated with development
      of AD, and may serve as potential targets for the treatment of AD.

PMID- 19765190
TI  - Neuro-inflammation induced in the hippocampus of 'binge drinking' rats may be
      mediated by elevated extracellular glutamate content.
AB  - The neuropathological and immune changes induced in the brain by 'binge drinking'
      have been investigated in a rat model. Evidence of neuro-inflammation was
      identified in the 'binge drinking' rat model of alcohol abuse after 3 weeks of
      administration of 2 or 3 g/kg ethanol (EtOH), three times per day for two
      consecutive days, followed by 5 days of abstinence: Firstly, alveolar
      macrophages, isolated from these animals, showed significant increases in
      inducible nitric oxide synthase, as assayed by nitrite release, both before and
      after lipopolysaccaharide stimulation. Secondly, significant numbers of activated
      microglia were present in the dentate gyrus region of the hippocampus of the
      'binge drinking' model, after major histocompatibility complex class II staining,
      by comparison with the control. Microdialysis studies in the ventral hippocampus
      identified a significant increase in the basal extracellular concentration of
      glutamate, in both the 2 and 3 g/kg administered 'binge drinking' rats. In
      contrast, no changes in the hippocampal extracellular concentrations, of GABA and
      taurine, or the dopamine and serotonin metabolites were observed under basal
      conditions. A further dose of EtOH induced a significant decrease in the
      concentrations of both 3,4-dihydroxyphenylacetic acid and 5-hydroxyindoleacetic
      acid, whereas glutamate, taurine and GABA levels were unaffected. There was no
      evidence that EtOH preference was initiated by the 'binge drinking' regimen. Our
      results suggest that the possible toxicity associated with 'binge drinking' maybe
      directed by the elevated glutamate levels, which in turn, activate phagocytic
      cells to release their inflammatory cytokines and chemokines, ultimately leading
      to neuro-inflammation.

PMID- 19765191
TI  - Sequestosome 1/p62 links familial ALS mutant SOD1 to LC3 via an ubiquitin
      independent mechanism.
AB  - The p62/sequestosome 1 protein has been identified as a component of pathological
      protein inclusions in neurodegenerative diseases including amyotrophic lateral
      sclerosis (ALS). P62 has also been implicated in autophagy, a process of mass
      degradation of intracellular proteins and organelles. Autophagy is a critical
      pathway for degrading misfolded and/or damaged proteins, including the copper
      zinc superoxide dismutase (SOD1) mutants linked to familial ALS. We previously
      reported that p62 interacted with ALS mutants of SOD1 and that the ubiquitin
      association domain of p62 was dispensable for the interaction. In this study, we
      identified two distinct regions of p62 that were essential to its binding to
      mutant SOD1: the N-terminal Phox and Bem1 (PB1) domain (residues 1-104) and a
      separate internal region (residues 178-224) termed here as SOD1 mutant
      interaction region (SMIR). The PB1 domain is required for appropriate oligomeric
      status of p62 and the SMIR is the actual region interacting with mutant SOD1.
      Within the SMIR, the conserved W184, H190 and positively charged R183, R186,
      K187, and K189 residues are critical to the p62-mutant SOD1 interaction as
      substitution of these residues with alanine resulted in significantly abolished
      binding. In addition, SMIR and the p62 sequence responsible for the interaction
      with LC3, a protein essential for autophagy activation, are independent of each
      other. In cells lacking p62, the existence of mutant SOD1 in acidic autolysosomes
      decreased, suggesting that p62 can function as an adaptor between mutant SOD1 and
      the autophagy machinery. This study provides a novel molecular mechanism by which
      mutant SOD1 can be recognized by p62 in an ubiquitin-independent fashion and
      targeted for the autophagy-lysosome degradation pathway.

PMID- 19765192
TI  - Structure of alpha6 beta3 delta GABA(A) receptors and their lack of ethanol
      sensitivity.
AB  - Delta (delta) subunit containing GABA(A) receptors are expressed extra
      synaptically and mediate tonic inhibition. In cerebellar granule cells, they
      often form a receptor together with alpha(6) subunits. We were interested to
      determine the architecture of these receptors. We predefined the subunit
      arrangement of 24 different GABA(A) receptor pentamers by subunit concatenation.
      These receptors (composed of alpha(6), beta(3) and delta subunits) were expressed
      in Xenopus oocytes and their electrophysiological properties analyzed. Currents
      elicited in response to GABA were determined in presence and absence of 3alpha,
      21-dihydroxy-5alpha-pregnan-20-one and to 4,5,6,7-tetrahydroisoxazolo[5,4-c]
      pyridin-3-ol. alpha(6)-beta(3)-alpha(6)/delta receptors showed a substantial
      response to GABA alone. Three receptors, beta(3)-alpha(6)-delta/alpha(6)-beta(3),
      alpha(6)-beta(3)-alpha(6)/beta(3)-delta and beta(3)-delta-beta(3)/alpha(6)
      beta(3), were only uncovered in the combined presence of the neurosteroid 3alpha,
      21-dihydroxy-5alpha-pregnan-20-one with GABA. All four receptors were activated
      by 4,5,6,7-tetrahydroisoxazolo[5,4-c]-pyridin-3-ol. None of the functional
      receptors was modulated by physiological concentrations (up to 30 mM) of ethanol.
      GABA concentration response curves indicated that the delta subunit can
      contribute to the formation of an agonist site. We conclude from the investigated
      receptors that the delta subunit can assume multiple positions in a receptor
      pentamer composed of alpha(6), beta(3) and delta subunits.

PMID- 19765193
TI  - Immunoreactivity of the phosphorylated axonal neurofilament H subunit (pNF-H) in
      blood of ALS model rodents and ALS patients: evaluation of blood pNF-H as a
      potential ALS biomarker.
AB  - Levels of neurofilament subunits, potential biomarkers of motor axon breakdown,
      are increased in amyotrophic lateral sclerosis (ALS) patient's CSF but data on
      blood are not available. We measured blood levels of the phosphorylated axonal
      form of neurofilament H (pNF-H) by ELISA in transgenic rodent models of
      superoxide dismutase 1 (SOD1) ALS, and in 20 ALS patients and 20 similar aged
      controls monthly for 4 months. All symptomatic rodent ALS models showed robust
      levels of blood pNF-H, while control rodents or mice transgenic for unmutated
      SOD1 showed no detectable blood pNF-H. Average pNF-H levels in the G93A SOD1
      mouse progressively increased from day 74 through death (day approximately 130).
      Median blood pNF-H level in ALS patients was 2.8-fold higher than controls (p <
      0.001). Median ALSFRS-R declined a median of 0.8 pt/month (p < 0.001); higher
      baseline pNF-H level appeared to be associated with faster ALSFRS-R decline over
      4 months (p = 0.087). The median rate of decline in ALSFRS-R was 1.9 pt/month in
      patients with baseline pNF-H levels above the median pNF-H value of 0.53 ng/mL;
      ALSFRS-R declined at a median of 0.6 pt/month in patients below this level. The
      pNF-H levels were relatively stable month to month in individual patients,
      raising questions regarding the molecular pathogenesis of ALS. Baseline control
      human pNF-H levels were higher in men than women and increased minimally over
      time. These data suggest that blood pNF-H can be used to monitor axonal
      degeneration in ALS model rodents and support further study of this protein as a
      potential biomarker of disease prognosis in ALS patients.

PMID- 19765195
TI  - Distance between the medialis angles of the eyes as an anatomical parameter for
      tooth selection.
AB  - During the construction of a removable prosthesis, the lack of pre-extractions
      records turns the selection of artificial maxillary anterior teeth into a complex
      procedure. The aim of this study was to identify a mathematical relation between
      the anterior dental segment and the distance between the medialis angles of the
      eyes, for selecting the suitable width of the six maxillary anterior teeth.
      Standardized digital images of 80 dentate Brazilian subjects were used to measure
      both facial and oral structures when viewed from the frontal aspect through an
      image processing program. Accurate casts were made to measure on a curve the
      distance between the maxillary canines. Parametric statistics was performed to
      analyse the results (P < 0.05). The distance between the medialis angles of the
      eyes showed no significant difference according to gender (P < 0.108). The
      Pearson Product Moment Correlation Coefficient showed significant positive
      correlation between the distance between the medialis angles of the eyes and all
      variables compared. After the linear regression analysis, mathematical formulae
      and biometric ratios were concluded to estimate the combined width of the six
      maxillary anterior teeth from the measurement of the distance between the
      medialis angles of the eyes. The distance between the medialis angles of the eyes
      measured through photogrammetry can be a reliable guide for tooth selection.

PMID- 19765194
TI  - Valproic acid induces functional heat-shock protein 70 via Class I histone
      deacetylase inhibition in cortical neurons: a potential role of Sp1 acetylation.
AB  - Neuroprotective properties of the mood stabilizer valproic acid (VPA) are
      implicated in its therapeutic efficacy. Heat-shock protein 70 (HSP70) is a
      molecular chaperone, neuroprotective and anti-inflammatory agent. This study
      aimed to investigate underlying mechanisms and functional significance of HSP70
      induction by VPA in rat cortical neurons. VPA treatment markedly up-regulated
      HSP70 protein levels, and this was accompanied by increased HSP70 mRNA levels and
      promoter hyperacetylation and activity. Other HDAC inhibitors--sodium butyrate,
      trichostatin A, and Class I HDAC-specific inhibitors MS-275 and apicidin, --all
      mimicked the ability of VPA to induce HSP70. Pre-treatment with
      phosphatidylinositol 3-kinase inhibitors or an Akt inhibitor attenuated HSP70
      induction by VPA and other HDAC inhibitors. VPA treatment increased Sp1
      acetylation, and a Sp1 inhibitor, mithramycin, abolished the induction of HSP70
      by HDAC inhibitors. Moreover, VPA promoted the association of Sp1 with the
      histone acetyltransferases p300 and recruitment of p300 to the HSP70 promoter.
      Further, VPA-induced neuroprotection against glutamate excitotoxicity was
      prevented by blocking HSP70 induction. Taken together, the data suggest that the
      phosphatidylinositol 3-kinase/Akt pathway and Sp1 are likely involved in HSP70
      induction by HDAC inhibitors, and induction of HSP70 by VPA in cortical neurons
      may contribute to its neuroprotective and therapeutic effects.

PMID- 19765196
TI  - Variability of mechanical torque-limiting devices in clinical service at a US
      dental school.
AB  - PURPOSE: The purpose of this study was to measure the variability of torque
      produced by a population of mechanical torque-limiting devices in clinical
      service in a US dental school. The torque-limiting devices were divided into two
      categories according to their mode of action: toggle-type and beam wrenches.
      Proper action of these devices is essential for calibrated delivery of preload to
      implant prosthetic screws. MATERIALS AND METHODS: Seventeen torque-limiting
      devices (35 Ncm) were obtained from graduate prosthodontic, predoctoral, and
      faculty practice clinics. Nine of these were toggle-type devices, and eight were
      beam-type wrenches. Torque from each wrench was measured using an MGT electronic
      torque meter. Wrenches were tested in two modes, slow (over 4 seconds) and fast
      (over 1 second). RESULTS: Toggle-type torque wrenches produced a mean (+/- SD)
      torque of 38.1 +/- 16.0 Ncm; beam-type wrenches produced 32.8 +/- 1.1 Ncm. These
      results were not significantly different. When tested in fast mode (1 second),
      toggle-type wrenches produced 28.0 +/- 9.6 Ncm; in the slow mode (4 seconds) they
      produced significantly more force, 36.6 +/- 14.0 Ncm (p < 0.001). Beam-type
      wrenches produced 33.2 +/- 1.1 Ncm and 32.8 +/- 1.1 Ncm in fast and slow modes,
      respectively. CONCLUSIONS: Both types of wrenches tested were capable of
      producing accurate torque values; however, variability was higher in the toggle
      type group. Some toggle-type torque wrenches in clinical service delivered
      unacceptably high torque values. It is recommended that clinicians calibrate
      toggle-type wrenches frequently. Torque wrenches should be activated slowly, over
      4 seconds, when using a correctly calibrated toggle-type wrench.

PMID- 19765197
TI  - The retention of cast metal dowels fabricated by direct and indirect techniques.
AB  - PURPOSE: To explore the effect of fabrication technique, cement type, and
      cementation procedure on retention of cast metal dowels. METHODS AND MATERIALS:
      Eighty intact single-rooted teeth were selected. The clinical crown was removed
      at the cementoenamel junction level. Each root was prepared to receive a cast
      metal dowel of 10-mm length and 1.45 mm in diameter. The 80 specimens were
      divided into two major groups of 40 based on fabrication technique (direct and
      indirect). Each group was further divided into four subgroups of ten based on the
      cement type (zinc phosphate and glass ionomer), and cementation procedure (with
      and without lentulo spiral). The dowels were subjected to a constantly increasing
      tensile force, in a universal Instron testing machine, at crosshead speed of 5
      mm/min until failure. RESULTS: The most significant factor to affect retention
      was the cementation procedure, as cementation with lentulo spiral produced
      greater retention than cementation without the use of lentulo spiral (p < 0.05);
      however, there seems to be a close interaction between fabrication technique,
      cement type, and cementation procedure (p= 0.051). The least retentive group was
      the one fabricated by direct technique, cemented with zinc phosphate without the
      use of lentulo spiral. CONCLUSION: Fabrication technique does not affect
      retention of cast dowels, except when zinc phosphate was the luting agent and
      placed in the canal space without using a lentulo spiral. The cementation
      procedure had a significant effect on retention; thus, it is recommended that
      cementation should be done using the lentulo spiral.

PMID- 19765198
TI  - Analysis of masticatory cycle efficiency in complete denture wearers.
AB  - PURPOSE: This study assessed masticatory efficiency and duration of the
      masticatory cycle in 14 asymptomatic patients with severe bone resorption. All
      patients had worn complete dentures for over 10 years. Recall visits were
      scheduled at 5 months and 1 year after receiving new dentures. MATERIALS AND
      METHODS: Fourteen patients were evaluated in this study. The Research Diagnostic
      Criteria questionnaire and tests of the efficiency and duration of the
      masticatory cycle were performed with artificial food before, 5 months after, and
      1 year after new dentures were delivered. Masticatory efficiency was assessed
      using a sieve system; artificial food was ground for 35 masticatory cycles and
      monitored by the operator. RESULTS: Masticatory efficiency at 5 months was
      significantly improved for the 0.42-mm mesh. An improvement in masticatory
      efficiency and a reduction in mastication time were observed with the new
      dentures after 1 year. CONCLUSION: The results of this study indicated that 5
      months did not allow enough time to demonstrate improved muscular capacity and
      ability after receiving new dentures. After 1 year, the duration of the
      masticatory cycle was reduced, and masticatory efficiency was significantly
      improved.

PMID- 19765199
TI  - The effect of bleaching agents on the surface topography of ceramometal dental
      alloys.
AB  - PURPOSE: To study the effect of bleaching agents on the surface topography of
      ceramometal alloys. MATERIALS AND METHODS: Three types of ceramometal alloys were
      used (gold, Ni-Cr, Co-Cr-Ti), and two types of bleaching agents (an agent
      intended for home use, one intended for use in the dental office) were studied.
      Forty-five specimens were constructed and divided according to the alloy type
      into three main groups, 15 specimens per group. Each group was further subdivided
      into three subgroups according to the type of bleaching agent used. The first
      subgroup (five specimens) was not subjected to any bleaching agent. The second
      and third subgroups were subjected to home and in-office bleaching agents,
      respectively. RESULTS: Au alloy showed the least surface roughness when subjected
      to either of the two bleaching agents. Ni-Cr alloys showed the highest surface
      roughness for both the control and home bleached subgroups, and Co-Cr-Ti alloy
      showed the highest surface roughness in the in-office bleached subgroup. No
      statistically significant difference was found between the control subgroup and
      the home-bleached subgroup for either the Au alloy or the Co-Cr-Ti alloy. For the
      two alloys, both the control and home-bleached subgroups were statistically
      different from the in-office bleached subgroups. There was a statistically
      significant difference between the Ni-Cr control subgroup and the other two
      bleached subgroups, while there was no difference between the two bleached
      subgroups. Results also showed that increasing the concentration of bleaching
      agents increased the surface roughness of all the tested alloys. There was a
      statistical difference between the Ni-Cr alloy and the other two alloys in all
      tested subgroups except the in-office bleached subgroup, for which no difference
      between the surface roughness of the Ni-Cr alloy and the Co-Cr-Ti alloy was
      found. Scanning electron microscopic examination revealed surface deteriorations
      in the two bleached subgroups for all tested ceramometallic alloys. CONCLUSION:
      Surface topographic alterations occurred as a result of the application of
      bleaching agents. These alterations increased with the increase of the carbamide
      peroxide concentration.

PMID- 19765200
TI  - Assessing oral cancer early detection: clarifying dentists' practices.
AB  - OBJECTIVE: This study explores new methods for assessing in greater detail what
      dentists do when they perform oral cancer early detection examinations. It
      clarifies practice behaviors and opens opportunities to identify factors that
      facilitate thorough early detection examinations by clinicians and to assess the
      relative effectiveness of different examination procedures. METHODS: A 38-item
      survey instrument was e-mailed to dentists in a western US, multistate dental
      practice group. Questionnaires were received by 241 dentists, and 102 responded.
      An Oral Cancer Knowledge scale (0 to 14) was generated from correct responses on
      oral cancer general knowledge. An Oral Cancer Examination Thoroughness scale was
      calculated from the two dimensions of reported usage and frequency of procedures
      in oral cancer examinations. RESULTS: Nearly all responding dentists were in
      general practice (90%), with a median year of graduation from dental school of
      1994. The Oral Cancer Knowledge scores ranged from 5 to 14 with a mean of 10.4.
      The mean Thoroughness of Examination score was 11.34 (range 0 to 20). The two
      scales were not statistically correlated (r = -0.015, P = 0.883). Statistically,
      recency of continuing education was significantly associated with knowledge (P =
      0.0284) and appears to be marginally associated with thoroughness (P = 0.075).
      CONCLUSIONS: This study documents considerable variability in dentists' knowledge
      and thoroughness of examinations. The scales provide tools for future studies for
      improving understanding of early detection of oral cancer in clinical practice.

PMID- 19765201
TI  - Influences of adult-onset diabetes on orofacial pain and related health
      behaviors.
AB  - OBJECTIVES: This study tested the hypothesis that persons with orofacial pain and
      comorbid adult-onset diabetes will experience greater functional and emotional
      impact than persons experiencing orofacial pain without diabetes. METHODS: A
      random-digit dialing sampling procedure was used for a disproportionate
      probability sample of 10,341 persons who were screened for orofacial pain in the
      past 6 months and diabetes. This paper reports on 1,767 individuals reporting
      toothache pain and 877 reporting painful oral sores. A structured telephone
      interview assessed diabetes history, orofacial pain characteristics, oral health
      care behaviors, and emotional and functional impacts of orofacial pain. RESULTS:
      The 6-month point prevalence was 16.8 percent for toothache pain, 8.9 percent for
      painful oral sores, and 9.6 percent for adult-onset diabetes. Individuals with
      comorbid orofacial pain and adult-onset diabetes differed significantly on many
      of the pain characteristics and health behaviors compared with nondiabetic
      sufferers of orofacial pain. Diabetics were more likely than nondiabetics to have
      pain every day, to suffer negative emotions associated with pain, to experience
      disruption of daily activities and sleep, to make an emergency room visit for
      orofacial pain, and to report the current need for a pain-related health-care
      visit. CONCLUSIONS: Although diabetes is well known to be associated with
      neuropathic pain, these results indicate that the experience of nociceptive pain
      is exacerbated by diabetes. Findings have significance for the subjective
      experience of oral pain, dental-care outcomes, and health-related quality of life
      associated with oral-health outcomes among individuals with diabetes.

PMID- 19765202
TI  - Increasing dental care utilization by Medicaid-eligible children: a dental care
      coordinator intervention.
AB  - OBJECTIVES: The aim of this study was to determine the effect of a dental care
      coordinator intervention on increasing dental utilization by Medicaid-eligible
      children compared with a control group. METHODS: One hundred and thirty-six
      children enrolled in Medicaid aged 4 to 15 years at baseline in 2004 who had not
      had Medicaid claims for 2 years, were randomly assigned to intervention or
      control groups for 12 months. Children and caregivers in the intervention group
      received education, assistance in finding a dentist if the child did not have
      one, and assistance and support in scheduling and keeping dental appointments.
      All children continued to receive routine member services from the dental plan
      administrator, including newsletters and benefit updates during the study.
      RESULTS: Dental utilization during the study period was significantly higher in
      the intervention group (43 percent) than in the control group (26 percent). The
      effect was even more significant among children living in households well below
      the Federal Poverty Level. The intervention was effective regardless of whether
      the coordinator was able to provide services in person or via telephone and mail.
      CONCLUSION: The dental care coordinator intervention significantly increased
      dental utilization compared with similar children who received routine Medicaid
      member services. Public health programs and communities endeavoring to reduce
      oral health disparities may want to consider incorporating a dental care
      coordinator along with other initiatives to increase dental utilization by
      disadvantaged children.

PMID- 19765203
TI  - Dental care utilization and retirement.
AB  - OBJECTIVE: The authors examine the relationship of dental care coverage,
      retirement, and utilization in an aging population using data from the Health and
      Retirement Study (HRS). METHODS: The authors estimate dental care use as a
      function of dental care coverage status, retirement, and individual and household
      characteristics. They also estimate a multivariate model controlling for
      potentially confounding variables. RESULTS: The authors show that that the loss
      of income and dental coverage associated with retirement may lead to lower use
      rates but this effect may be offset by other unobserved aspects of retirement
      including more available free time leading to an overall higher use rate.
      CONCLUSIONS: The authors conclude from this study that full retirement
      accompanied by reduced income and dental insurance coverage produces lower
      utilization of dental services. However, they also show that retirement acts as
      an independent variable, whereas income, coverage, and free time (unobserved) act
      as intervening variables.

PMID- 19765204
TI  - Nanoparticles as a novel delivery vehicle for therapeutics targeting erectile
      dysfunction.
AB  - INTRODUCTION: Nanoparticles represent a potential novel mechanism for transdermal
      delivery of erectogenic agents directly to the penis. AIM: To determine if
      nanoparticles encapsulating known erectogenic agents (tadalafil, sialorphin, and
      nitric oxide [NO]) can improve erectile function in a rat model of erectile
      dysfunction (ED) as a result of aging (the Sprague-Dawley retired breeder rat).
      METHODS: Nanoparticles encapsulating the erectogenic agents were applied as a gel
      to the glans and penile shaft of anesthetized Sprague-Dawley rats and the
      intracorporal pressure/blood pressure (ICP/BP) monitored for up to 2 hours with
      or without stimulation of the cavernous nerve. Control nanoparticles were made
      without encapsulating erectogenic agents and applied in a similar manner in
      separate experiments. RESULTS: Nanoparticles encapsulating NO caused spontaneous
      visible erections in the rat, with an average time of onset of 4.5 minutes,
      duration of 1.42 minutes, and ICP/BP of 0.67 +/- 0.14. The sialorphin
      nanoparticles also caused visible spontaneous erections after an average of 4.5
      minutes, with a duration of 8 minutes and ICP/BP ratio of 0.72 +/- 0.13. The
      difference in the erectile response between groups of animals treated with NO or
      sialorphin nanoparticles was significantly different from the control group
      treated with empty nanoparticles (P < 0.05) Tadalafil nanoparticles showed a
      significant increase in the mean ICP/BP (0.737 +/- 0.029) following stimulation
      of the cavernous nerve (4 mA) 1 hour after application of the nanoparticles with
      a visibly improved erectile response. CONCLUSIONS: Nanoparticles encapsulating
      three different erectogenic agents resulted in increased erectile function when
      applied to the penis of a rat model of ED. Nanoparticles represent a potential
      novel route for topical delivery of erectogenic agents which could improve the
      safety profile for existing orally administered drugs by avoiding effects of
      absorption and first-pass metabolism, and would be less hazardous than injection.

PMID- 19765205
TI  - Treatment effects on brain activity during a working memory task in obstructive
      sleep apnea.
AB  - Positive airway pressure (PAP) is the most common form of treatment for
      obstructive sleep apnea (OSA). Treatment adherence is notoriously low, and
      holidays from treatment are common. To date, there is no literature on the
      effects of acute withdrawal from PAP treatment on the brain activity of
      individuals with OSA. Nine participants with OSA performed a 2-Back verbal
      working memory paradigm during repeated functional magnetic resonance imaging
      (FMRI). Counterbalanced FMRI sessions were under conditions of PAP treatment (at
      least one consecutive week) or non-treatment (for two consecutive nights).
      Treatment effects on 2-Back-related brain activity were significant, with greater
      deactivation in the right posterior insula and overactivation in the right
      inferior parietal lobule. The observed responses to PAP treatment withdrawal were
      more extreme in all regions of interest, such that 2-Back-related activity
      increased and 2-Back-related deactivation decreased further relative to the 0
      Back control task. The withdrawal of PAP treatment in effectively treated
      individuals with OSA might result in the need to reallocate resources in order to
      perform at the same cognitive level.

PMID- 19765206
TI  - Hypoxia-induced changes in recovery sleep, core body temperature, urinary 6
      sulphatoxymelatonin and free cortisol after a simulated long-duration flight.
AB  - Fatigue and sleep disorders often occur after long-haul flights, even when no
      time zones are crossed. In this controlled study, we assessed the effects of two
      levels of hypoxia (at 8000 ft and 12 000 ft) on recovery sleep. Core body
      temperature (CBT), a circadian marker, urinary 6-sulphatoxymelatonin and free
      cortisol were studied in 20 young healthy male volunteers exposed for 8 h (08:00
      16:00 hours) in a hypobaric chamber to a simulated cabin altitude of 8000 ft and,
      4 weeks later, 12 000 ft. Each subject served as his own control. Sleep was
      recorded by polysomnography for three consecutive nights for each exposure. CBT
      was monitored by telemetry during the three 24-h cycles (control, hypoxic
      exposure and recovery). Free urinary cortisol and 6-sulphatoxymelatonin levels
      were assayed twice daily between 08:00 and 20:00 hours (day) and between 20:00
      and 08:00 hours (night). We showed significant changes in circadian patterns of
      CBT at both altitudes, suggesting a phase delay, and changes in recovery sleep
      but only at 12 000 ft. We observed an increase in sleep onset latency which
      correlated positively with the increase in CBT levels during the first recovery
      night and a decrease in the duration of stage N(2) (formerly S(2)), which
      correlated negatively with the mid-range crossing time, a reliable phase marker
      of CBT rhythm. This study shows clearly the impact of hypobaric hypoxia on
      circadian time structure during air flights leading to a phase delay of CBT,
      independent of jet lag and consequences on sleep during recovery.

PMID- 19765207
TI  - Will oral rivaroxaban improve clinically relevant outcomes and thromboprophylaxis
      management in the orthopedic patient?

PMID- 19765208
TI  - Association between genetic variation at the ADAMTS13 locus and ischemic stroke.

PMID- 19765209
TI  - Interlaboratory agreement in the monitoring of unfractionated heparin using the
      anti-factor Xa-correlated activated partial thromboplastin time: a rebuttal.

PMID- 19765211
TI  - Circulating ADAMTS-13-von Willebrand factor complexes: an enzyme on demand.

PMID- 19765210
TI  - The molecular basis of factor V and VIII procofactor activation.
AB  - Activation of precursor proteins by specific and limited proteolysis is a
      hallmark of the hemostatic process. The homologous coagulation factors (F)V and
      FVIII circulate in an inactive, quiescent state in blood. In this so-called
      procofactor state, these proteins have little, if any procoagulant activity and
      do not participate to any significant degree in their respective macromolecular
      enzymatic complexes. Thrombin is considered a key physiological activator,
      cleaving select peptide bonds in FV and FVIII which ultimately leads to
      appropriate structural changes that impart cofactor function. As the active
      cofactors (FVa and FVIIIa) have an enormous impact on thrombin and FXa
      generation, maintaining FV and FVIII as inactive procofactors undoubtedly plays
      an important regulatory role that has likely evolved to maintain normal
      hemostasis. Over the past three decades there has been widespread interest in
      studying the proteolytic events that lead to the activation of these proteins.
      While a great deal has been learned, mechanistic explanations as to how bond
      cleavage facilitates conversion to the active cofactor species remain
      incompletely understood. However, recent advances have been made detailing how
      thrombin recognizes FV and FVIII and also how the FV B-domain plays a dominant
      role in maintaining the procofactor state. Here we review our current
      understanding of the molecular process of procofactor activation with a
      particular emphasis on FV.

PMID- 19765212
TI  - Multi-step binding of ADAMTS-13 to von Willebrand factor.
AB  - BACKGROUND: ADAMTS-13 proteolytic activity is controlled by the conformation of
      its substrate, von Willebrand factor (VWF), and changes in the secondary
      structure of VWF are essential for efficient cleavage. Substrate recognition is
      mediated through several non-catalytic domains in ADAMTS-13 distant from the
      active site. OBJECTIVES: We hypothesized that not all binding sites for ADAMTS-13
      in VWF are cryptic and analyzed binding of native VWF to ADAMTS-13. METHODS:
      Immunoprecipiation of VWF-ADAMTS-13 complexes using anti-VWF antibodies and
      magnetic beads was used. Binding was assessed by Western blotting and
      immunosorbent assays. RESULTS: Co-immunoprecipitation demonstrated that ADAMTS-13
      binds to native multimeric VWF (K(d) of 79 +/- 11 nmol L(-1)) with no measurable
      proteolysis. Upon shear-induced unfolding of VWF, binding increased 3-fold and
      VWF was cleaved. Binding to native VWF was saturable, time dependent, reversible
      and did not vary with ionic strength (I of 50-200). Moreover, results with ADAMTS
      13 deletion mutants indicated that binding to native VWF is mediated through
      domains distal to the ADAMTS-13 spacer, probably thrombospondin-1 repeats.
      Interestingly, this interaction occurs in normal human plasma with an ADAMTS-13
      to VWF stoichiometry of 0.0040 +/- 0.0004 (mean +/- SEM, n = 10). CONCLUSIONS:
      ADAMTS-13 binds to circulating VWF and may therefore be incorporated into a
      platelet-rich thrombus, where it can immediately cleave VWF that is unfolded by
      fluid shear stress.

PMID- 19765213
TI  - Nitric oxide inhibits von Willebrand factor-mediated platelet adhesion and
      spreading through regulation of integrin alpha(IIb)beta(3) and myosin light
      chain.
AB  - BACKGROUND: von Willebrand factor (VWF)-mediated platelet adhesion and spreading
      at sites of vascular injury is a critical step in hemostasis. This process
      requires two individual receptors: glycoprotein Ib (GPIb)-V-IX and integrin
      alpha(IIb)beta(3). However, little is known about the negative regulation of
      these events. OBJECTIVES: To examine if the endogenous platelet inhibitor nitric
      oxide (NO) has differential effects on adhesion, spreading and aggregation
      induced by immobilized VWF. RESULTS: S-nitrosoglutathione (GSNO) inhibited
      platelet aggregation on immobilized VWF under static and flow conditions, but had
      no effect on platelet adhesion. Primary signaling events underpinning the actions
      of NO required cyclic GMP but not protein kinase A. Dissecting the roles of GPIb
      and integrin alpha(IIb)beta(3) demonstrated that NO targeted alpha(IIb)beta(3)
      mediated aggregation and spreading, but did not significantly influence GPIb
      mediated adhesion. To understand the relationship between the effects of NO on
      adhesion and subsequent aggregation, we evaluated the activation of
      alpha(IIb)beta(3) on adherent platelets. NO reduced the phosphorylation of
      extracellular stimuli-responsive kinase (ERK) and p38, required for integrin
      activation resulting in reduced binding of the activated alpha(IIb)beta(3)
      specific antibody PAC-1 on adherent platelets. Detailed analysis of platelet
      spreading initiated by VWF demonstrated key roles for integrin alpha(IIb)beta(3)
      and myosin light chain (MLC) phosphorylation. NO targeted both of these pathways
      by directly modulating integrin affinity and activating MLC phosphatase.
      CONCLUSION: These data demonstrate that initial activation-independent platelet
      adhesion to VWF via GPIb is resistant to NO, however, NO inhibits GPIb-mediated
      activation of alpha(IIb)beta(3) and MLC leading to reduced platelet spreading and
      aggregation.

PMID- 19765214
TI  - Chronic degenerative valvular disease--where are we now?

PMID- 19765215
TI  - Neurohormonal activation in canine degenerative mitral valve disease:
      implications on pathophysiology and treatment.
AB  - Neurohormonal systems play a critical role in canine degenerative mitral valve
      disease (DMVD). DMVD results in mitral regurgitation, which reduces forward
      cardiac output and increases intracardiac pressures. These changes trigger
      neurohormonal responses that ultimately result in maladaptive cardiac
      remodelling, congestion and heightened morbidity and mortality. Medical therapies
      such as ACE inhibitors and spironolactone derive their benefit by interrupting or
      suppressing these neurohormonal responses. Thus, knowledge of neurohormonal
      mechanisms can lead to a better understanding of how to treat DMVD.

PMID- 19765216
TI  - Can ventricular function be assessed by echocardiography in chronic canine mitral
      valve disease?
AB  - Mitral regurgitation (MR) related to chronic degenerative valvular disease is the
      most important cause of heart failure in dogs. Ultrasound examination of the
      heart can identify valve lesions, confirm the presence of valvular regurgitation,
      document cardiac remodeling, estimate intracardiac pressures, and quantify
      systolic ventricular function. These findings can influence prognosis or
      selection of medical therapy. Reductions in ventricular systolic function may be
      detected on serial echocardiographic examinations in some dogs with MR. However
      the changes in ventricular loading that accompany MR often complicate these
      measurements. For example, shortening and ejection fractions are often increased
      in severe MR, even in the setting of congestive heart failure. Echocardiography
      with Doppler is also used to assess ventricular diastolic function and filling
      pressures. This information helps predict the risk of congestive heart failure.
      However these findings are often rendered ambiguous by age-related impairment of
      ventricular relaxation, elevations in left atrial pressure due to MR, and effects
      of volume overload on myocardial tissue velocities. These factors limit the
      usefulness of ventricular filling and tissue velocities, as well as derived
      ratios such as the E/E' ratio, for predicting congestive heart failure in MR.
      More advanced Doppler and tissue echocardiographic methods, as well as
      prospective clinical studies, are needed to reduce the ambiguity involved with
      assessment of ventricular function and filling pressures in the setting of MR.

PMID- 19765217
TI  - An update on treatment and prognostic indicators in canine myxomatous mitral
      valve disease.
AB  - Mitral regurgitation caused by myxomatous mitral valve disease is the most common
      cause for congestive heart failure and cardiac-related mortality in dogs.
      Typically, it takes several years for the disease to progress from mild,
      clinically silent myxomatous mitral valve disease to severe disease with signs of
      congestive heart failure. A proportion of dogs will never progress into
      congestive heart failure before they die from other causes or old age. Some
      variables have been shown to be predictive of onset of congestive heart failure
      and they might be useful to identify dogs that need more frequent monitoring and
      eventually treatment. Results from several controlled clinical trials are
      available concerning medical treatment of dogs with myxomatous mitral valve
      disease with or without congestive heart failure. These trials provide estimates
      of treatment effects and also allow identification of other variables with
      prognostic value for the outcome after the onset of congestive heart failure. Use
      of prognostic variables together with qualitative and quantitative results from
      clinical drug trials may aid the clinician and owner to plan and decide on
      optimal management of the myxomatous mitral valve disease dog. The purpose of
      this article is to review the current knowledge of prognostic variables and
      therapy for this common condition in dogs.

PMID- 19765218
TI  - Pulmonary arterial hypertension secondary to chronic left-sided cardiac
      dysfunction in dogs.
AB  - Pulmonary arterial hypertension is a description of a physiological finding
      rather than a diagnosis. Pulmonary arterial pressure is the result of
      interactions among pulmonary blood flow (right ventricular cardiac output),
      pulmonary vascular impedance and post-capillary pressure (typically reflecting
      left atrial pressure). When elevations in pulmonary arterial pressure
      (systolic/diastolic pulmonary arterial pressure > approximately 30/19 mmHg at
      rest) are accompanied by increased left atrial pressure, pulmonary arterial
      hypertension may be considered secondary to left-heart failure. Introduction of
      Doppler methods to diagnose pulmonary arterial hypertension has increased the
      awareness of the prevalence and importance of pulmonary arterial hypertension
      dogs with left-heart failure. Increasing understanding of the mechanism of
      development of pulmonary venous hypertension and reactive pulmonary arterial
      hypertension in dogs with left-heart disease has led to the development of
      successful additive therapies for progressive clinical signs in the setting of
      chronic therapy for congestive heart failure due to left-sided valvular and
      myocardial dysfunction. Because effective therapies for pulmonary arterial
      hypertension secondary to chronic left-sided cardiac dysfunction are now
      available, screening for pulmonary arterial hypertension should be a regular part
      of the Doppler echocardiographic examination in a clinical setting of chronic
      therapy for left-sided congestive heart failure due to valvular or myocardial
      disease.

PMID- 19765219
TI  - Reader performance in radiographic diagnosis of signs of mitral regurgitation in
      cavalier King Charles spaniels.
AB  - OBJECTIVES: To measure accuracy and variability of diagnosis by radiography of
      heart enlargement (HE) and heart failure (HF) in mitral regurgitation (MR).
      METHODS: Sixteen readers representing four levels of experience evaluated 50 sets
      of radiographs with varying severity of MR for presence or absence of HE, left
      atrial enlargement (LAE) and HF. The performance of the readers was compared with
      a reference standard, using area under the curve (AUC) of receiver operating
      characteristic (ROC) curves. The interreader agreement value kappa (K) was
      calculated. A subset of difficult cases of HF was analysed before and after
      removing an outlying reader from each group. RESULTS: AUC for HE was 0.89, for
      LAE it was 0.93 and for HF it was 0.92. Experience increased certainty of
      diagnosis but not accuracy. K ranges were HE, 0.53 to 0.67; LAE, 0.61 to 0.69 and
      HF, 0.49 to 0.58. When only difficult cases of HF were read, accuracy decreased
      and experienced readers performed better than inexperienced. When outlying
      readers were excluded, the differences between experienced and inexperienced
      readers increased. CLINICAL SIGNIFICANCE: LAE, not HE, should be used to evaluate
      the heart size and indirectly the severity of MR on radiographs. For HF,
      agreement among individual readers was only moderate. Studies of reader accuracy
      should consider the effects of interreader variability.

PMID- 19765220
TI  - Increased bactericidal/permeability increasing protein in patients with
      cirrhosis.
AB  - BACKGROUND: High levels of endotoxin in patients with cirrhosis are thought to be
      responsible for the activation of tumour necrosis factor-alpha (TNF)-alpha
      mediated pro-inflammatory pathways involved in haemodynamic alterations.
      Bactericidal/permeability increasing protein (BPI) is a protein found in
      neutrophils with endotoxin-binding and neutralization capacity. It is not known
      whether defective BPI production or release is present in cirrhosis. AIMS: We
      investigated the levels of BPI in cirrhotic patients and its relation to other
      endotoxin-binding proteins and inflammatory markers. METHODS: Plasmatic levels of
      BPI, lipopolysaccharide-binding protein, soluble CD14, TNF-alpha and BPI mRNA
      expression in neutrophils were determined in 130 patients and 30 healthy
      controls. The capacity of patients' plasma to inhibit lipopolysaccharide (LPS)
      mediated TNF-alpha production by monocytes from healthy donors was assessed in
      vitro. RESULTS: Patients with cirrhosis exhibited an increase in BPI mRNA and
      plasma level of BPI when compared with healthy controls (P<0.05). Child C group
      displayed the highest frequency of patients with a high concentration of BPI. A
      positive correlation was found between TNF-alpha and plasma levels of BPI
      (P<0.01). High levels of BPI in plasma were able to significantly reduce in vitro
      TNF-alpha release by monocytes after a challenge with LPS (8.54 +/- 1.04 vs.
      10.44 +/- 0.85 pg/ml, P=0.028). CONCLUSION: BPI is increased in cirrhotic
      patients, especially in those with more severe liver disease. The amount of BPI
      in the plasma correlated with the TNF-alpha level and was able to reduce LPS
      mediated TNF production by monocytes. BPI possibly plays a regulatory role by
      antagonizing the pro-inflammatory mechanisms mediated by TNF-alpha.

PMID- 19765222
TI  - Seasonal and latitudinal acclimatization of cardiac transcriptome responses to
      thermal stress in porcelain crabs, Petrolisthes cinctipes.
AB  - Central predictions of climate warming models include increased climate
      variability and increased severity of heat waves. Physiological acclimatization
      in populations across large-scale ecological gradients in habitat temperature
      fluctuation is an important factor to consider in detecting responses to climate
      change related increases in thermal fluctuation. We measured in vivo cardiac
      thermal maxima and used microarrays to profile transcriptome heat and cold stress
      responses in cardiac tissue of intertidal zone porcelain crabs across
      biogeographic and seasonal gradients in habitat temperature fluctuation. We
      observed acclimatization dependent induction of heat shock proteins, as well as
      unknown genes with heat shock protein-like expression profiles. Thermal
      acclimatization had the largest effect on heat stress responses of extensin-like,
      beta tubulin, and unknown genes. For these genes, crabs acclimatized to thermally
      variable sites had higher constitutive expression than specimens from low
      variability sites, but heat stress dramatically induced expression in specimens
      from low variability sites and repressed expression in specimens from highly
      variable sites. Our application of ecological transcriptomics has yielded new
      biomarkers that may represent sensitive indicators of acclimatization to habitat
      temperature fluctuation. Our study also has identified novel genes whose further
      description may yield novel understanding of cellular responses to thermal
      acclimatization or thermal stress.

PMID- 19765223
TI  - Marker-assisted determination of the relationship between body size and
      reproductive success and consequences for evaluation of adaptive life histories.
AB  - We tested for differences in the predicted optimal ages at first maturity in
      brook charr (Salvelinus fontinalis) in Freshwater River, Newfoundland, when life
      history data were collated based on the marker-assisted estimation of the
      relationship between body size and reproductive success rather than using
      fecundity as a surrogate for reproductive success. Jointly with capture-recapture
      data to estimate the growth and survival costs of reproduction, we found that
      weak relationships between body size and reproductive success generate selection
      against delayed maturation. This finding would not have held for females if the
      relationship between body size and fecundity had been used as a surrogate for the
      relationship between body size and reproductive success. This shows that
      predictions of optimal life histories can be qualitatively changed when using
      molecular markers to directly evaluate age- and/or size-specific effects of body
      size on reproductive success.

PMID- 19765224
TI  - Abstracts of the 4th Trends in Medical Mycology. October 18-21, 2009. Athens,
      Greece.

PMID- 19765225
TI  - An information-theoretical approach to phylogeography.
AB  - Data analysis in phylogeographic investigations is typically conducted in either
      a qualitative manner, or alternatively via the testing of null hypotheses. The
      former, where inferences about population processes are derived from geographical
      patterns of genetic variation, may be subject to confirmation bias and prone to
      overinterpretation. Testing the predictions of null hypotheses is arguably less
      prone to bias than qualitative approaches, but only if the tested hypotheses are
      biologically meaningful. As it is difficult to know a priori if this is the case,
      there is the general need for additional methodological approaches in
      phylogeographic research. Here, we explore an alternative method for analysing
      phylogeographic data that utilizes information theory to quantify the probability
      of multiple hypotheses given the data. We accomplish this by augmenting the model
      selection procedure implemented in ima with calculations of Akaike Information
      Criterion scores and model probabilities. We generate a ranking of 17 models each
      representing a set of historical evolutionary processes that may have contributed
      to the evolution of Plethodon idahoensis, and then quantify the relative strength
      of support for each hypothesis given the data using metrics borrowed from
      information theory. Our results suggest that two models have high probability
      given the data. Each of these models includes population divergence and estimates
      of ancestral theta that differ from estimates of descendent theta, inferences
      consistent with prior work in this system. However, the models disagree in that
      one includes migration as a parameter and one does not, suggesting that there are
      two regions of parameter space that produce model likelihoods that are similar in
      magnitude given our data. Results of a simulation study suggest that when data
      are simulated with migration, most of the optimal models include migration as a
      parameter, and further that when all of the shared polymorphism results from
      incomplete lineage sorting, most of the optimal models do not. The results could
      also indicate a lack of precision, which may be a product of the amount of data
      that we have collected. In any case, the information-theoretic metrics that we
      have applied to the analysis of our data are statistically rigorous, as are
      hypothesis-testing approaches, but move beyond the 'reject/fail to reject'
      dichotomy of conventional hypothesis testing in a manner that provides
      considerably more flexibility to researchers.

PMID- 19765226
TI  - Lack of global population genetic differentiation in the arbuscular mycorrhizal
      fungus Glomus mosseae suggests a recent range expansion which may have coincided
      with the spread of agriculture.
AB  - The arbuscular mycorrhizal fungus Glomus mosseae is commonly found in
      agricultural fields. The cosmopolitan species is found in Africa, Europe,
      America, Asia and Australia. Three hypotheses may explain this worldwide
      distribution: First, speciation occurred before the continents separated 120 Ma;
      second, the distribution is a result of human-mediated dispersal related to
      agriculture and finally, the morphologically defined species may encompass
      several local endemic species. To test these hypotheses, three genes were
      sequenced from 82 isolates of G. mosseae originating from six continents and the
      resulting sequences analysed for geographical subdivision and estimation of
      migration between continents. Coalescent analyses estimated divergence and age of
      mutations. Bayesian coalescent modelling was used to reveal important past
      population changes in the global population. The sequence data showed no
      geographical structure, with identical genotypes found on different continents.
      Coalescence analyses indicated a recent diversification in the species, and the
      data could be explained by a recent population expansion in G. mosseae. The
      results of this study suggest that speciation and the range expansion happened
      much later than continental spread and that human activity may have had a major
      impact on the dispersal and the population structure of the fungus.

PMID- 19765227
TI  - Conservation genetics of Amorpha georgiana (Fabaceae), an endangered legume of
      the Southeastern United States.
AB  - Amorpha georgiana (Fabaceae) is an endangered legume species found in longleaf
      pine savannas in the Southeastern United States. Approximately 900 individuals
      and 14 populations remain, most of which are concentrated in North Carolina.
      Eleven microsatellite loci were used to explore genetic diversity, population
      structure and recent population bottlenecks using genotypic data from 132
      individuals collected at ten different localities. Although A. georgiana is quite
      rare, it exhibited high levels of genetic diversity (17.7 alleles/locus; H(o) =
      0.65, H(E) = 0.75). Most of the genetic variation was found within rather than
      between populations of this species. The single remaining Georgia population was
      well differentiated from populations of the Carolinas (F(ST) > 0.1), which had
      weaker structure among them (F(ST) < 0.1). Only a geographically disjunct
      population showed strong evidence of a recent population bottleneck, perhaps due
      to a recent founder event. Hybridization with A. herbacea was also detected. For
      conservation management plans, A. georgiana populations in each geographic region
      (North Carolina, South Carolina and Georgia) plus a disjunct population in North
      Carolina (Holly Shelter) should be treated as separate management units for which
      in situ conservation, including habitat restoration and use of prescribed burns,
      should ensure persistence of this species and preservation of its evolutionary
      potential.

PMID- 19765228
TI  - Implications of isolation and low genetic diversity in peripheral populations of
      an amphi-Atlantic coral.
AB  - Limited dispersal and connectivity in marine organisms can have negative fitness
      effects in populations that are small and isolated, but reduced genetic exchange
      may also promote the potential for local adaptation. Here, we compare the levels
      of genetic diversity and connectivity in the coral Montastraea cavernosa among
      both central and peripheral populations throughout its range in the Atlantic.
      Genetic data from one mitochondrial and two nuclear loci in 191 individuals show
      that M. cavernosa is subdivided into three genetically distinct regions in the
      Atlantic: Caribbean-North Atlantic, Western South Atlantic (Brazil) and Eastern
      Tropical Atlantic (West Africa). Within each region, populations have similar
      allele frequencies and levels of genetic diversity; indeed, no significant
      differentiation was found between populations separated by as much as 3000 km,
      suggesting that this coral species has the ability to disperse over large
      distances. Gene flow within regions does not, however, translate into
      connectivity across the entire Atlantic. Instead, substantial differences in
      allele frequencies across regions suggest that genetic exchange is infrequent
      between the Caribbean, Brazil and West Africa. Furthermore, markedly lower levels
      of genetic diversity are observed in the Brazilian and West African populations.
      Genetic diversity and connectivity may contribute to the resilience of a coral
      population to disturbance. Isolated peripheral populations may be more vulnerable
      to human impacts, disease or climate change relative to those in the genetically
      diverse Caribbean-North Atlantic region.

PMID- 19765229
TI  - A putative novel transcription factor, AtSKIP, is involved in abscisic acid
      signalling and confers salt and osmotic tolerance in Arabidopsis.
AB  - We identified and functionally characterized the AtSKIP gene (At1g77180), an
      Arabidopsis homologue of SNW/SKIP, under abiotic stresses. Although the SNW/SKIP
      protein has been implicated as a critical transcription cofactor, its biological
      functions have yet to be reported in any plant. Recently, we have isolated Salt
      tolerance genes (SATs) via the overexpression screening of yeast with a maize
      cDNA library. One of the selected genes (SAT2) appeared to confer elevated
      tolerance to salt. Maize SAT2 cDNA encodes a homologue of the human SNW/SKIP
      transcriptional coregulator. Treatment with salt, mannitol and abscisic acid
      induced AtSKIP expression. Ectopic expression of the AtSKIP gene modulated the
      induction of salt tolerance, dehydration resistance and insensitivity towards
      abscisic acid under stress conditions. By contrast, atskip antisense lines
      displayed reduced tolerance to abiotic stresses during germination. Moreover, a
      decrease in AtSKIP expression resulted in an abnormal phenotype. We further
      determined that the AtSKIP protein activated the transcription of a reporter gene
      in yeast. Green fluorescent protein-tagged AtSKIP was localized in the nuclei of
      both onion cells and transgenic Arabidopsis cells. Taken together, these results
      suggest that AtSKIP functions as both a positive regulator and putative potential
      transcription factor in the abiotic stress signalling pathway.

PMID- 19765230
TI  - Global and cell-type gene expression profiles in tomato plants colonized by an
      arbuscular mycorrhizal fungus.
AB  - *Arbuscular mycorrhizal symbiosis develops in roots; extensive cellular
      reorganizations and specific metabolic changes occur, which are mirrored by local
      and systemic changes in the transcript profiles. *A TOM2 microarray (c. 12 000
      probes) has been used to obtain an overview of the transcriptional changes that
      are triggered in Solanum lycopersicum roots and shoots, as a result of
      colonization by the arbuscular mycorrhizal fungus Glomus mosseae. The cell-type
      expression profile of a subset of genes was monitored, using laser
      microdissection, to identify possible plant determinants of arbuscule
      development,. *Microarrays revealed 362 up-regulated and 293 down-regulated genes
      in roots. Significant gene modulation was also observed in shoots: 85 up- and 337
      down-regulated genes. The most responsive genes in both organs were ascribed to
      primary and secondary metabolism, defence and response to stimuli, cell
      organization and protein modification, and transcriptional regulation. Six genes,
      preferentially expressed in arbusculated cells, were identified. *A comparative
      analysis only showed a limited overlap with transcript profiles identified in
      mycorrhizal roots of Medicago truncatula, probably as a consequence of the
      largely nonoverlapping probe sets on the microarray tools used. The results
      suggest that auxin and abscisic acid metabolism are involved in arbuscule
      formation and/or functioning.

PMID- 19765231
TI  - Apoplastic barriers effectively block oxygen permeability across outer cell
      layers of rice roots under deoxygenated conditions: roles of apoplastic pores and
      of respiration.
AB  - *Despite the importance of the barrier to oxygen losses of the roots of
      hygrophytes growing in wet environments devoid of oxygen, there are few data
      available on permeability coefficients for O(2) across outer root cell layers
      (P(OPR)) and how they may change in response to low O(2). *A gas perfusion
      technique was used to measure the P(OPR) of rice (Oryza sativa) plants grown in
      either aerated or deoxygenated solution. The contributions of the apoplast and of
      living cells to the overall P(OPR) were characterized either by blocking
      apoplastic pores with precipitates of brown Cu(2)[Fe(CN)(6)] or by killing cells
      with 0.1 N HCl. *Compared with that of plants from aerated hydroponics, the
      P(OPR) of plants grown in deoxygenated medium was smaller by an order of
      magnitude. Precipitates resulting from CuSO(4)/K(4)[Fe(CN)(6)] treatment only
      formed in plants grown in aerated solution, where they reduced the P(OPR) by 5
      20%. Killing of root segments with HCl increased P(OPR) in plants grown in both
      conditions by 20-55%. *The results indicated that apoplastic barriers effectively
      restricted radial O(2) loss. The relative role of the respiratory O(2)
      consumption of root peripheral layers increased as P(OPR) decreased.

PMID- 19765232
TI  - The prevalence of impaired fasting glucose and type 2 diabetes in a population
      based sample of overweight/obese children in the Middle East.
AB  - BACKGROUND: Type 2 diabetes mellitus (T2DM) and impaired fasting glucose (IFG)
      are increasing in young population who are facing an escalating trend of
      overweight. The aim of this study was to determine the prevalence of IFG and T2DM
      for the first time in a population-based sample of Iranian obese children.
      METHODS: This cross-sectional, population-based study was conducted in Isfahan,
      the second large city of Iran. Overall, 672 overweight and obese school students,
      selected from 7554 students, aged 6-19 yr, were screened for IFG and T2DM.
      Fasting plasma glucose (FPG) and lipid profile were measured in all participants.
      Oral glucose tolerance test and insulin level were measured in those children
      with IFG. Insulin resistance was defined as homeostasis model assessment for
      insulin resistance (HOMA-IR) > 3.10. RESULTS: Among the7554 students (48.7% boys
      and 51.3% girls) studied, 9.34% (n = 706) were overweight and 5.3% (n = 403) were
      obese. A number of 672 overweight and obese students including 302 (44.9%) boys
      and 370 (55.1%) girls, with a mean age of 12.8 +/- 3.10 yr underwent biochemical
      work up. Overall, the prevalence of IFG was 4.61% (n = 31), the corresponding
      figure was 2% (n = 4) in the 6-10 yr age group, and 5% (n = 27) in those aged
      10.1-19 yr. The prevalence of T2DM was 0.1% (n = 1; age, 18.00 yr). Impaired
      glucose tolerance and insulin resistance were detected in three and six
      participants with IFG, who consisted 0.4 and 0.8% of total obese and overweight
      students, respectively. CONCLUSIONS: Although the prevalence of T2DM is low in
      Iranian obese children, IFG is not uncommon. Preventive measures and screening of
      FPG should be considered for these children.

PMID- 19765233
TI  - Assessment of resynchronization therapy on functional status and quality of life
      in patients requiring an implantable defibrillator.
AB  - BACKGROUND: The effect of cardiac resynchronization therapy (CRT) on physical
      function and Quality of Life (QoL) in patients who require an implantable
      defibrillator but do not meet guideline criteria for CRT has not been studied in
      detail. METHODS AND RESULTS: This was a randomized study of 72 patients with high
      risk of sudden cardiac death, ejection fraction (EF) < or =35%, mild-to-moderate
      heart failure symptoms, and QRS > 120 ms. Patients received a CRT defibrillator
      and were randomized to CRT turned ON or OFF. Objective and subjective measures
      were performed at baseline and after 6 months. There was no difference in change
      in left ventricular end-systolic volume (ESV) by radionuclid angiogram scan, the
      primary endpoint, between the CRT ON group (DeltaESV =-7 +/- 52 mL), and CRT OFF
      group (DeltaESV =-30 +/- 47 mL). Similarly, echocardiogram measures of ESV and EF
      showed no difference between the two groups. In the CRT ON group, selected
      measures of QoL and subjective exercise tolerance but not heart failure symptoms
      improved significantly. Six-minute walk distance prolonged in the CRT ON group
      (baseline 313.6 +/- 114.4 m, 6-month 365.0 +/- 122.5 m, P = 0.01), but the
      difference in change in walk distance between the two groups was not significant.
      CONCLUSION: Further studies with larger sample size and longer follow-up will be
      required to allow definite conclusions regarding the potential benefit of CRT in
      this patient population.

PMID- 19765234
TI  - Jasmonate controls late development stages of petal growth in Arabidopsis
      thaliana.
AB  - In Arabidopsis, four homeotic gene classes, A, B, C and E, are required for the
      patterning of floral organs. However, very little is known about how the activity
      of these master genes is translated into regulatory processes leading to specific
      growth patterns and the formation of organs with specific shapes and sizes.
      Previously we showed that the transcript variant BPEp encodes a bHLH
      transcription factor that is involved in limiting petal size by controlling post
      mitotic cell expansion. Here we show that the phytohormone jasmonate is required
      for control of BPEp expression. Expression of BPEp was negatively regulated in
      opr3 mutant flowers that are deficient in jasmonate synthesis. Moreover, the
      expression of BPEp was restored in opr3 flowers following exogenous jasmonate
      treatments. Expression of the second transcript variant BPEub, which originates
      from the same gene as BPEp via an alternative splicing event, was not affected,
      indicating that BPEp accumulation triggered by jasmonate occurs at the post
      transcriptional level. Consistent with these data, opr3 exhibited an increase in
      petal size as a result of increased cell size, as well as a modified vein
      pattern, phenotypes that are similar to those of the bpe-1 mutant. Furthermore,
      exogenous treatments with jasmonate rescued petal phenotypes associated with loss
      of function of OPR3. Our data demonstrate that jasmonate signaling downstream of
      OPR3 is involved in the control of cell expansion and in limiting petal size, and
      that BPEp is a downstream target that functions as a component mediating
      jasmonate signaling during petal growth.

PMID- 19765235
TI  - Rice cellulose synthase-like D4 is essential for normal cell-wall biosynthesis
      and plant growth.
AB  - Cellulose synthase-like (CSL) proteins of glycosyltransferase family 2 (GT2) are
      believed to be involved in the biosynthesis of cell-wall polymers. The CSL D sub
      family (CSLD) is common to all plants, but the functions of CSLDs remain to be
      elucidated. We report here an in-depth characterization of a narrow leaf and
      dwarf1 (nd1) rice mutant that shows significant reduction in plant growth due to
      retarded cell division. Map-based cloning revealed that ND1 encodes OsCSLD4, one
      of five members of the CSLD sub-family in rice. OsCSLD4 is mainly expressed in
      tissues undergoing rapid growth. Expression of OsCSLD4 fluorescently tagged at
      the C- or N-terminus in rice protoplast cells or Nicotiana benthamiana leaves
      showed that the protein is located in the endoplasmic reticulum or Golgi
      vesicles. Golgi localization was verified using phenotype-rescued transgenic
      plants expressing OsCSLD4-GUS under the control of its own promoter. Two
      phenotype-altered tissues, culms and root tips, were used to investigate the
      specific wall defects. Immunological studies and monosaccharide compositional and
      glycosyl linkage analyses explored several wall compositional effects caused by
      disruption of OsCSLD4, including alterations in the structure of arabinoxylan and
      the content of cellulose and homogalacturonan, which are distinct in the monocot
      grass species Oryza sativa (rice). The inconsistent alterations in the two
      tissues and the observable structural defects in primary walls indicate that
      OsCSLD4 plays important roles in cell-wall formation and plant growth.

PMID- 19765236
TI  - The left hand doesn't know what the right hand is doing: the disruptive effects
      of attention to the hands in skilled typewriting.
AB  - Everyone knows that attention to the details disrupts skilled performance, but
      little empirical evidence documents this fact. We show that attention to the
      hands disrupts skilled typewriting. We had skilled typists type words preceded by
      cues that told them to type only the letters assigned to one hand or to type all
      of the letters. Cuing the hands disrupted performance markedly, slowing typing
      and increasing the error rate (Experiment 1); these deleterious effects were
      observed even when no keystrokes were actually inhibited (Experiment 3). However,
      cuing the same letters with colors was not disruptive (Experiment 2). We account
      for the disruption with a hierarchical control model, in which an inner loop
      controls the hands and an outer loop controls what is typed. Typing letters using
      only one hand requires the outer loop to monitor the inner loop's output; the
      outer loop slows inner-loop cycle time to increase the likelihood of inhibiting
      responses with the unwanted hand. This produces the disruption.

PMID- 19765237
TI  - How does stigma "get under the skin"?: the mediating role of emotion regulation.
AB  - Stigma is a risk factor for mental health problems, but few studies have
      considered how stigma leads to psychological distress. The present research
      examined whether specific emotion-regulation strategies account for the stigma
      distress association. In an experience-sampling study, rumination and suppression
      occurred more on days when stigma-related stressors were reported than on days
      when these stressors were not reported, and rumination mediated the relationship
      between stigma-related stress and psychological distress. The effect of social
      support on distress was moderated by the concealability of the stigma: Lesbian,
      gay, and bisexual (LGB) respondents reported more isolation and less social
      support than African American respondents subsequent to experiencing stigma
      related stressors, whereas African Americans reported greater social support than
      LGB participants. Social isolation mediated the stigma-distress association among
      LGB respondents. In a second experimental study, participants who ruminated
      following the recall of an autobiographical discrimination event exhibited
      prolonged distress on both implicit and explicit measures relative to
      participants who distracted themselves; this finding provides support for a
      causal role of rumination in the stigma-distress relationship.

PMID- 19765238
TI  - Two forms of spatial imagery: neuroimaging evidence.
AB  - Spatial imagery may be useful in such tasks as interpreting graphs and solving
      geometry problems, and even in performing surgery. This study provides evidence
      that spatial imagery is not a single faculty; rather, visualizing spatial
      location and mentally transforming location rely on distinct neural networks.
      Using 3-T functional magnetic resonance imaging, we tested 16 participants (8
      male, 8 female) in each of two spatial imagery tasks--one that required
      visualizing location and one that required mentally rotating stimuli. The same
      stimuli were used in the two tasks. The location-based task engendered more
      activation near the occipito-parietal sulcus, medial posterior cingulate, and
      precuneus, whereas the transformation task engendered more activation in superior
      portions of the parietal lobe and in the postcentral gyrus. These differences in
      activation provide evidence that there are at least two different types of
      spatial imagery.

PMID- 19765239
TI  - Superimposed vibration confers no additional benefit compared with resistance
      training alone.
AB  - Eighteen participants (22-43 years) were randomly allocated to one of two groups:
      resistance training combined with vibration (VIB; five males, four females) or
      resistance training alone (CON; five males, four females). Each participant
      trained three sessions per week (three sets of 10 seated calf raises against a
      load, which was increased progressively from 75% of one repetition maximum (1RM)
      to 90% 1RM for 4 weeks. For the VIB group, a vibratory stimulus (30 Hz, 2.5 mm
      amplitude) was applied to the soles of the feet by a vibration platform. The two
      groups did not differ significantly with respect to the total amount of work
      performed during training. Both groups showed a significant increase in maximum
      voluntary contraction and 1RM (P<0.01) with training. There were no significant
      changes in measures that assessed the rate at which force was developed.
      Countermovement jump height increased for the CON (P<0.01) but not for the VIB
      group. Comparisons between the groups revealed that they did not differ
      significantly from one another with respect to any measure of performance, before
      or following training. It appears that vibration superimposed upon resistance
      training does not alter or augment the increase in strength induced by resistance
      training alone.

PMID- 19765240
TI  - Gender differences in the incidence and prevalence of patellofemoral pain
      syndrome.
AB  - The purpose of this investigation was to determine the association between gender
      and the prevalence and incidence of patellofemoral pain syndrome (PFPS). One
      thousand five hundred and twenty-five participants from the United States Naval
      Academy (USNA) were followed for up to 2.5 years for the development of PFPS.
      Physicians and certified athletic trainers documented the cases of PFPS. PFPS was
      defined as retropatellar pain during at least two of the following activities:
      ascending/descending stairs, hopping/jogging, prolonged sitting, kneeling, and
      squatting, negative findings on examination of knee ligament, menisci, bursa, and
      synovial plica, and pain on palpation of either the patellar facets or femoral
      condyles. Poisson and logistic regressions were performed to determine the
      association between gender and the incidence and prevalence of PFPS,
      respectively. The incidence rate for PFPS was 22/1000 person-years. Females were
      2.23 times (95% CI: 1.19, 4.20) more likely to develop PFPS compared with males.
      While not statistically significant, the prevalence of PFPS at study enrollment
      tended to be higher in females (15%) than in males (12%) (P=0.09). Females at the
      USNA are significantly more likely to develop PFPS than males. Additionally, at
      the time of admission to the academy, the prevalence of PFPS was not
      significantly different between genders.

PMID- 19765241
TI  - A study of semi-rigid support on ankle supination sprain kinematics.
AB  - Ankle sprain injury is very common in sports and the use of ankle support is
      crucial. This research investigated the effect of an ankle brace in reducing the
      ankle angular displacement and angular velocity during sudden supination. In the
      experiment, 11 healthy males were tested. The bracing condition, semi-rigid ankle
      braces were investigated. The angular displacement and angular velocity of the
      ankle were computed. The motion-capture system was adopted to capture the three
      dimensional coordinates of the reflective markers. The coordinates of the
      reflective markers were used to compute the ankle kinematics during simulated
      ankle supination. A mechanical supination platform was used to simulate the
      sprain motions. Experimental results showed that the semi-rigid brace tested
      significantly reduced the ankle angular displacement and angular velocity
      compared with control conditions during sudden supination. In conclusion, the
      semi-rigid-type brace can provide significant restriction to reduce the
      magnitudes of the angular displacement and angular velocity of the ankle during
      sudden supination sprain. The semi-rigid-type brace is suggested as the
      prophylactic bracing for the ankle.

PMID- 19765242
TI  - Differences in the inflammatory plasma cytokine response following two elite
      female soccer games separated by a 72-h recovery.
AB  - We investigated changes in a large battery of pro- and anti-inflammatory
      cytokines in elite female soccer players following two 90-min games separated by
      a 72-h active or passive recovery. Blood samples were taken from 10 players
      before, within 15-20 min, 21, 45 and 69 h after the first game and within 15-20
      min after the second game. The leukocyte count was analyzed, together with
      several plasma pro- and anti-inflammatory cytokines, using a multiplex bead array
      system. After the first and second game, the total leukocytes and neutrophils
      increased significantly. Likewise, increases (P<0.05) in pro-inflammatory
      cytokines [interleukin (IL)-12, tumor necrosis factor-alpha (TNF-alpha),
      interferon-gamma (INF-gamma), IL-17], chemokines [monocyte chemotactic protein-1
      (MCP-1), IL-8 and monokine induced by gamma interferon (MIG)], anti-inflammatory
      cytokines (IL-2R, IL-4, IL-5, IL-7, IL-10, IL-13, INF-alpha) and the mixed
      cytokine IL-6 were observed. Leukocyte and cytokine levels were normalized within
      21 h. Active recovery (low-intensity exercises) did not affect the cytokine
      responses. A dampened cytokine response was observed after the second game as
      only IL-12, IL-6, MCP-1, IL-8 and MIG increased (P<0.05). In conclusion, a robust
      pro- and anti-inflammatory cytokine response occurs after the first but not the
      second soccer game. The implications of the dampened cytokine response in female
      players after the second game are unknown.

PMID- 19765243
TI  - The biology of satellite cells and telomeres in human skeletal muscle: effects of
      aging and physical activity.
AB  - The decline in the neuromuscular function affects the physical performance and is
      a threat for independent living in later life. The age-related decrease in muscle
      satellite cells observed by the age of 70 can be specific to type II fibers in
      some muscles. Several studies have shown that different forms of exercise induce
      the expansion of satellite cell pool in human skeletal muscle of young and
      elderly. Exercise is a powerful non-pharmacological tool inducing the renewal of
      the satellite cell pool in skeletal muscles. Skeletal muscle is not a stable
      tissue as satellite cells are constantly recruited during normal daily
      activities. Satellite cells and the length of telomeres are important in the
      context of muscle regeneration. It is likely that the regulation of telomeres in
      vitro cannot fully mimic the behavior of telomeres in human tissues. New insights
      suggest that telomeres in skeletal muscle are dynamic structures under the
      influence of their environment. When satellite cells are heavily recruited for
      regenerative events as in the skeletal muscle of athletes, telomere length has
      been found to be either dramatically shortened or maintained and even longer than
      in non-trained individuals. This suggests the existence of mechanisms allowing
      the control of telomere length in vivo.

PMID- 19765244
TI  - Differences in the radiological characteristics between post-traumatic and non
      traumatic knee osteoarthritis.
AB  - Osteoarthritis (OA) of the knee can be defined as primary (non-traumatic) or
      secondary (post-traumatic). Both non-traumatic OA and post-traumatic OA have been
      described predominantly in the medial compartment of the knee. The objective of
      this study was to compare the location of structural radiographic changes in non
      traumatic OA and post-traumatic OA. A non-traumatic cohort, consisting of 155
      patients suffering from chronic knee pain without known major injuries, was
      compared with a post-traumatic cohort, consisting of 176 patients, all of whom
      had sustained an anterior cruciate ligament injury while playing soccer. A
      standardized weight-bearing knee radiography of the tibiofemoral joint was
      performed. Joint space narrowing (JSN) and osteophytes were graded according to
      the radiographic atlas of the Osteoarthritis Research Society International. JSN
      and osteophytes were located predominantly in the medial compartment in the non
      traumatic cohort. In the post-traumatic cohort, structural changes were evenly
      distributed between the lateral and the medial compartments. We were thus able to
      demonstrate radiological differences between post-traumatic and non-traumatic OA.

PMID- 19765245
TI  - Cocoa Pod Borer (Conopomorpha cramerella Snellen) in Papua New Guinea:
      biosecurity models for New Ireland and the autonomous region of Bougainville.
AB  - Cocoa Pod Borer (Conopomorpha cramerella Snellen) (CPB) is an important pest of
      cocoa. Following its emergence as a pest in East New Britain, Papua New Guinea,
      in 2006, it was considered relevant to assess its potential spread to other cocoa
      growing regions. Its likelihood of introduction to the islands of Bougainville
      and New Ireland from East New Britain Province, Papua New Guinea, was modeled
      using Monte Carlo simulation. This dispersal model was based around different
      scenarios, identifying trends rather than explicitly attempting to encapsulate
      true values. The model suggested that CPB is far more likely to establish on New
      Ireland than on Bougainville. More important, incertitude resulting from
      incomplete knowledge of the amount and frequency of cocoa transported between
      islands had a significant effect on model outputs. Quarantine and agriculture
      officials will be able to refine these parameter values, and then use the
      relevant scenarios from those presented here as a guide to develop quarantine
      procedures. In addition, a contingency model was employed to estimate the optimal
      sampling effort to use following an incursion of CPB into Bougainville or New
      Ireland and the seemingly successful implementation of an initial eradication
      program. The model suggests that at a 1% infestation level, sampling should
      continue for 2.5-2.7 years (90% CI) after claiming eradication, and this estimate
      changed little for higher infestation levels. Through modeling variations in
      sampling intensity, the model also suggested that determining the full spread of
      CPB is more important than increased sampling within one region.

PMID- 19765246
TI  - Risk and causality in newspaper reporting.
AB  - The study addresses the textual representation of risk and causality in news
      media reporting. The analytical framework combines two theoretical perspectives:
      media frame analysis and the philosophy of causality. Empirical data derive from
      selected newspaper articles on risks in the Gota alv river valley in southwest
      Sweden from 1994 to 2007. News media content was coded and analyzed with respect
      to causal explanations of risk issues. At the level of individual articles, this
      study finds that the media provide simple causal explanations of risks such as
      water pollution, landslides, and flooding. Furthermore, these explanations are
      constructed, or framed, in various ways, the same risk being attributed to
      different causes in different articles. However, the study demonstrates that a
      fairly complex picture of risks in the media emerges when extensive material is
      analyzed systematically.

PMID- 19765248
TI  - Integrated approaches for the public health prioritization of foodborne and
      zoonotic pathogens.
AB  - To address the persistent problems of foodborne and zoonotic disease, public
      health officials worldwide face difficult choices about how to best allocate
      limited resources and target interventions to reduce morbidity and mortality.
      Data-driven approaches to informing these decisions have been developed in a
      number of countries. Integrated comparative frameworks generally share three
      methodological components: estimating incidence of acute illnesses, chronic
      sequelae, and mortality; attributing pathogen-specific illnesses to foods; and
      calculating integrated measures of disease burden such as cost of illness,
      willingness to pay, and health-adjusted life years (HALYs). To discuss the
      similarities and differences in these approaches, to seek consensus on
      principles, and to improve international collaboration, the E.U. MED-VET-NET and
      the U.S.-based Food Safety Research Consortium organized an international
      conference convened in Berlin, Germany, on July 19-21, 2006. This article draws
      in part on the deliberations of the conference and discusses general principles,
      data needs, methodological issues and challenges, and future research needs
      pertinent to objective data-driven analyses and their potential use for priority
      setting of foodborne and zoonotic pathogens in public health policy.

PMID- 19765249
TI  - Provision of a wildfire risk map: informing residents in the wildland urban
      interface.
AB  - Wildfires in the wildland urban interface (WUI) are an increasing concern
      throughout the western United States and elsewhere. WUI communities continue to
      grow and thus increase the wildfire risk to human lives and property. Information
      such as a wildfire risk map can inform WUI residents of potential risks and may
      help to efficiently sort mitigation efforts. This study uses the survey-based
      contingent valuation (CV) method to examine annual household willingness to pay
      (WTP) for the provision of a wildfire risk map. Data were collected through a
      mail survey of the East Mountain WUI area in the State of New Mexico (USA). The
      integrated empirical approach includes a system of equations that involves joint
      estimation of WTP values, along with measures of a respondent's risk perception
      and risk mitigation behavior. The median estimated WTP is around U.S. $12 for the
      annual wildfire risk map, which covers at least the costs of producing and
      distributing available risk information. Further, providing a wildfire risk map
      can help address policy goals emphasizing information gathering and sharing among
      stakeholders to mitigate the effects of wildfires.

PMID- 19765250
TI  - Using weight of evidence characterization and modeling to investigate the cause
      of the changes in Pacific herring (Clupea pallasi) population dynamics in Puget
      Sound and at Cherry Point, Washington.
AB  - The decline of the Cherry Point Pacific herring stock (CPPHS) has been a puzzle
      of the upper Puget Sound. In this study, age-structured population modeling was
      used to examine the timing and scale of the dynamics of Pacific herring stocks
      throughout the Puget Sound region. The intrinsic rate of increase and equilibrium
      age structure was calculated and forecast models were created for the stocks
      found in Puget Sound. We demonstrate that the causative agent for the decline of
      the CPPHS and the collapse in age structure existed in the 1974-1975 timeframe.
      Similarly, Puget Sound Pacific herring stocks at Squaxin Pass, Discovery Bay, and
      Port Gamble also demonstrate a collapse in age structure as seen in CPPHS during
      that same period. The data from the mid 1980s to 2006 demonstrate that all stocks
      share the collapse in age structure. The conclusion is that the causative agent
      had to affect these stocks at a scale corresponding to the Puget Sound; the
      effect has lasted over a 30-year period, and was essentially simultaneous across
      the region. Forecast modeling of the stocks indicates that given current
      conditions none of the stocks are likely to show an increase in population size.
      The results were used to examine the likelihood that the Eastern Pacific decadal
      oscillation, disease, and persistent organic pollutants are singularly or in
      concert the causative agents. A research program is suggested to determine the
      cause(s).

PMID- 19765251
TI  - Emerging roles of cinacalcet hydrochloride in the management of CKD-MBD.

PMID- 19765252
TI  - Clinical issues regarding cinacalcet hydrochloride in Japan.
AB  - Currently available cinacalcet hydrochloride has a greater advantage over
      conventional vitamin D therapy, although the ability of cinacalcet to suppress
      parathyroid hormone (PTH) varies among individuals. This article deals with the
      clinical issues of cinacalcet. Studies examining the impact of cinacalcet on
      parathyroid gland cells showed that cinacalcet may cause changes in PTH
      secretion, reduce the parathyroid gland size, and alter parathyroid gland
      function, suggesting the possibility that use of cinacalcet can eventually be
      stopped. Combined cinacalcet and vitamin D can reportedly increase vitamin D
      receptor expression. In a double-blind, placebo-controlled randomized study
      involving 1184 previously untreated secondary hyperparathyroidism (SHPT)
      patients, cinacalcet significantly reduced the likelihood of hospitalization for
      parathyroidectomy, fractures, and cardiovascular disease. Fibrous osteitis was
      suppressed in the rat model of renal failure treated with cinacalcet. Considering
      that the drug price of cinacalcet is lower in Japan than in the USA and Europe,
      it is highly likely that cinacalcet will be used to suppress PTH in Japan.

PMID- 19765253
TI  - Does cinacalcet improve the prognosis of dialysis patients?
AB  - Appropriate control of serum calcium (Ca) and inorganic phosphate (Pi) levels is
      required for better prognosis of dialysis patients. Cinacalcet is known to reduce
      not only serum parathyroid hormone (PTH) but also Ca and Pi levels; however, it
      remains unclear whether cinacalcet can ultimately improve the prognosis of such
      patients. In this paper, the ongoing prospective observational study (Q Cohort
      Study) and double-blind randomized controlled study (EVOLVE Study) are
      introduced. In the Q Cohort Study, cinacalcet therapy is indicated when intact
      PTH levels exceed 180 pg/mL, accounting for 31.3% of the study population (N =
      3009). In the EVOLVE Study, the primary endpoint is the time to occurrence of
      composite events including all-cause mortality or nonfatal cardiovascular events.
      There is a related pilot study that treated patients over a 6-month period with
      cinacalcet. The findings showed that cinacalcet reduced serum PTH, Ca, and Pi
      levels and that if the patient had lower PTH levels at baseline, the dosage of
      vitamin D could be greatly reduced. Thus, in some patients concomitant vitamin D
      and cinacalcet therapy may be preferred to vitamin D alone.

PMID- 19765254
TI  - Management of mineral and bone disorder in chronic kidney disease: quo vadis?
AB  - Mineral and bone disorder in chronic kidney disease (CKD-MBD) is a serious
      complication because of its profound impact on morbidity and mortality. Recent
      introduction of calcimimetic cinacalcet hydrochloride has led to a major
      breakthrough in the management of CKD-MBD. Numerous clinical studies have shown
      that in dialysis patients with secondary hyperparathyroidism, cinacalcet
      effectively reduces serum parathyroid hormone levels without increasing serum
      calcium and phosphorus levels. This is in contrast to vitamin D analogs that
      inhibit parathyroid hormone secretion at the price of enhanced intestinal
      absorption of calcium and phosphorus. More recent studies have focused on the
      efficacy of combination therapy with calcimimetics and low-dose vitamin D
      analogs. One of the most important issues in this context is whether treatment
      with cinacalcet results in improved clinical outcomes. This is currently under
      investigation by prospective clinical trials. However, many important questions
      remain unresolved, including issues with whether and how calcimimetics and
      vitamin D analogs should be combined and whether calcimimetics or vitamin D
      analogs should be preferred as primary therapy. With a view to improving patient
      level outcomes, further work should establish more precisely the role of
      calcimimetics and vitamin D analogs in combination with other therapeutic
      approaches for CKD-MBD management.

PMID- 19765255
TI  - Can cinacalcet replace parathyroid intervention in severe secondary
      hyperparathyroidism?
AB  - A 6-month observational study was conducted in 61 patients (33 men and 28 women,
      mean age 54.8 +/- 12.4 years) treated with cinacalcet in whom parathyroid
      intervention was indicated. Thirty-seven patients had baseline intact parathyroid
      hormone (iPTH) levels of >500 pg/mL, but only five still had levels this high
      after 6-month cinacalcet therapy. No patients had phosphorus (P), calcium (Ca),
      or iPTH levels within the target range at baseline, but six patients (9.8%)
      reached all three target ranges after treatment. The stratum with many patients
      who had 2-4 enlarged parathyroid glands shifted toward the low PTH groups (iPTH <
      300 pg/mL) with treatment. There was less of a tendency for patients with more
      enlarged glands, that is, 10 mm or larger at baseline, to have a higher PTH level
      after cinacalcet treatment. There was no significant difference in the total
      volume of parathyroid glands after treatment, since some glands enlarged while
      others shrank. These findings indicate cinacalcet to be a potentially useful
      treatment. Our results suggest that 80% of cases indicated for parathyroid
      intervention could avoid such interventional therapies with cinacalcet
      administration. However, the variability in the gland-shrinking effect of
      cinacalcet on parathyroid glands merits further study.

PMID- 19765256
TI  - Towards cost-effective strategies for treatment of chronic kidney disease-mineral
      and bone disorder in Japan.
AB  - There is a growing interest worldwide in making a more effective and efficient
      use of limited health care resources. Dialysis treatment in Japan and other
      countries is being confronted with increasing expenditure due to an aging
      population, coverage of new medical technologies, and an increase in the dialysis
      population. Chronic kidney disease-mineral and bone disorder (CKD-MBD) is an
      important issue related to the increased expenditure among dialysis patients
      because it is one of the main causes of morbidity and mortality, and results in a
      high economic burden. In recent years, several economic analyses on the treatment
      of CKD-MBD have been reported from Western countries. Given the longer dialysis
      vintage of Japanese patients, it is very important to conduct economic evaluation
      from a long-term viewpoint using clinical data on Japanese patients. This article
      reviews the recent literature on economic evaluation of CKD-MBD treatments and
      discusses the road ahead for cost-effectiveness analysis in Japanese dialysis
      patients with CKD-MBD.

PMID- 19765257
TI  - Cinacalcet in hyperfunctioning parathyroid diseases.
AB  - The calcium-sensing receptor (CaR) on the parathyroid cell surface senses ionized
      calcium concentration in the extracellular fluid and regulates minute-to-minute
      parathyroid hormone (PTH) secretion. Synthetic allosteric modulators of CaR have
      been developed, and one of the positive modulators (calcimimetics) is cinacalcet
      HCl or cinacalcet. Cinacalcet increases the sensitivity of CaR to be activated by
      extracellular calcium, and thus suppresses PTH release. Cinacalcet is an
      effective treatment for secondary hyperparathyroidism (SHPT) in patients with
      uremia on hemodialysis. In this review, based on basic experiments using
      cinacalcet, we postulate the beneficial effects of cinacalcet on hyperfunctioning
      parathyroid diseases.

PMID- 19765258
TI  - Genomic sequence of HLA-Cw*1222 allele identified in a Chinese Han patient from
      Southern China.
AB  - The genomic sequence of HLA-Cw*1222 allele is identical to Cw*120202 except for a
      single-nucleotide substitution at codon 87 (CAG-->CGG) resulting in an amino acid
      change from Gln to Arg.

PMID- 19765259
TI  - Genomic full length sequence of HLA-Cw*030301, identified by cloning and
      sequencing.
AB  - Genomic full length sequence of human leukocyte antigen (HLA)-Cw*030301 that
      differs from Cw*030401 by two-nucleotide exchange at nt 473 (G>A) in exon 2 and
      nt 3033 (G>C) in 3'UTR, was identified by cloning and sequencing from a male
      Chinese donor.

PMID- 19765260
TI  - Full length sequence of a novel HLA-B*3818 allele differs from HLA-B*380201
      allele in exon 4 and intron 5.
AB  - The full length sequence of HLA-B*3818 differs from HLA-B*380201 at nt 660 in
      exon 4 (C-->A) and genomic position 2133 in intron 5 (A-->C).

PMID- 19765261
TI  - Genetic determinants of HIV-1 infection and progression to AIDS: immune response
      genes.
AB  - Genomic studies involving well-defined multicenter cohorts of HIV-1/AIDS covering
      multiple populations have led to a greater understanding of the role of host
      determinants in viral acquisition, disease progression, transmission, and
      response to anti-retroviral therapy. Similarly, recent knowledge on the virus
      genetic diversity has helped in elucidating mechanisms leading to the evolution
      of viral escape mutants and the role played by host immune determinants, in
      particular the major histocompatibility complex (MHC) associated genes. At least
      two alleles, HLA-B*27 and B*57, have been identified as 'protective' against HIV
      1 while B*35 and B*53 act as susceptibility favoring factors. How human leukocyte
      antigen (HLA)-mediated selection drives the evolution of HIV-1 and which
      circulating variants are more likely to evade immune surveillance of the
      population are now beginning to become clear. Importantly, the rare HLA alleles
      in a population bear a selective advantage to the host because these can induce
      immune responses against pre-adapted viruses. It is conceivable that previously
      established protective HLA associations are shifting with the evolving cytotoxic
      T lymphocyte (CTL) epitopes and may not remain protective in future. At the same
      time, this process is unraveling novel sub-dominant epitopes of the virus which
      could now be incorporated as the dominant target CTL epitopes. An insight into
      the population-specific correlates of protection is hence necessary for designing
      future anti-HIV therapeutic and/or prophylactic vaccine formulation(s).

PMID- 19765262
TI  - A secretory Golgi bypass route to the apical surface domain of epithelial MDCK
      cells.
AB  - Proteins leave the endoplasmic reticulum (ER) for the plasma membrane via the
      classical secretory pathway, but routes bypassing the Golgi apparatus have also
      been observed. Apical and basolateral protein secretion in epithelial Madin-Darby
      canine kidney (MDCK) cells display differential sensitivity to Brefeldin A (BFA),
      where low concentrations retard apical transport, while basolateral transport
      still proceeds through intact Golgi cisternae. We now describe that BFA-mediated
      retardation of glycoprotein and proteoglycan transport through the Golgi
      apparatus induces surface transport of molecules lacking Golgi modifications,
      possessing those acquired in the ER. Low concentrations of BFA induces apical
      Golgi bypass, while higher concentrations were required to induce basolateral
      Golgi bypass. Addition of the KDEL ER-retrieval sequence to model protein cores
      allowed observation of apical Golgi bypass in untreated MDCK cells. Basolateral
      Golgi bypass was only observed after the addition of BFA or upon cholesterol
      depletion. Thus, in MDCK cells, an apical Golgi bypass route can transport cargo
      from pre-Golgi organelles in untreated cells, while the basolateral bypass route
      is inducible.

PMID- 19765263
TI  - Novel shuttling domain in a regulator (RSC1A1) of transporter SGLT1 steers cell
      cycle-dependent nuclear location.
AB  - The gene product of RSC1A1, RS1, participates in the regulation of the Na(+)-D
      glucose cotransporter SGLT1. RS1 inhibits release of SGLT1 from the trans Golgi
      network. In subconfluent LLC-PK(1) cells, RS1 migrates into the nucleus and
      modulates transcription of SGLT1, whereas most confluent cells do not contain RS1
      in the nuclei. We showed that confluence-dependent nuclear location of RS1 is
      because of different phases of the cell cycle and identified a RS1 nuclear
      shuttling domain (RNS) with an associated protein kinase C (PKC) phosphorylation
      site (RNS-PKC) that mediates cell cycle-dependent nuclear location. RNS-PKC
      contains a novel non-conventional nuclear localization signal interacting with
      importin beta1, a nuclear export signal mediating export via protein CRM1 and a
      Ca(2+)-dependent calmodulin binding site. PKC and calmodulin compete for binding
      to RNS-PKC. Mutagenesis experiments and analyses of the phosphorylation status
      suggest the following sequences of events. Subconfluent cells without and with
      synchronization to the G2/M phase contain non-phosphorylated RNS-PKC that
      mediates nuclear import of RS1 but not its export. During confluence or
      synchronization of subconfluent cells to the G2/M phase, phosphorylation of RNS
      PKC mediates rapid nuclear export of RS1.

PMID- 19765264
TI  - Live cell multicolor imaging of lipid droplets with a new dye, LD540.
AB  - A lipophilic dye based on the Bodipy fluorophore, LD540, was developed for
      microscopic imaging of lipid droplets. In contrast to previous lipid droplet
      dyes, it can spectrally be resolved from both green and red fluorophores allowing
      multicolor imaging in both fixed and living cells. Its improved specificity,
      brightness and photostability support live cell imaging, which was used to
      demonstrate by two-color imaging lipid droplet motility along microtubules.

PMID- 19765265
TI  - Cerebral coccidioidomycosis after renal transplantation in a non-endemic area.
AB  - Coccidioidomycosis is a fungal infection caused by Coccidioides species endemic
      to the desert south western United States. In healthy people, manifestations
      range mainly from asymptomatic to mild influenza-like syndrome. In
      immunosuppressed patients, extrapulmonary dissemination is common. We report the
      case of a patient with a parenchymal central nervous system lesion. This
      presentation is considered very rare. The highest risk of infection after solid
      organ transplantation occurs during the first year. Risk factors include
      treatment of acute rejection. In the reported case, the infection was probably
      donor-derived, as our patient had no history of traveling to endemic areas.
      Mortality is high among transplanted recipients with coccidioidomycosis,
      particularly those with disseminated infection.

PMID- 19765266
TI  - Multicentric outcome analysis of sirolimus-based immunosuppression in 252 liver
      transplant recipients.
AB  - SUMMARY: The use of sirolimus (SRL) in orthotopic liver transplantation (OLT) has
      been controversial after experimental data suggested an increased risk of hepatic
      artery thrombosis (HAT). To assess the safety and efficacy of SRL as de novo
      immunosuppression in OLT recipients. Outcomes of 252 OLT patients who received
      SRL were compared with outcomes of 291 OLT recipients who received calcineurin
      inhibitor in a retrospective study. Primary outcomes of this study were: patient-
      and graft survivals, vascular, biliary, wound complications and rejection rates.
      Secondary outcomes were: postoperative infection rate, bone marrow and renal
      function and changes of lipid levels. Patient- and graft survivals, rejection and
      infection rates were similar. In the SRL group, HAT occurred in 1.2%, biliary
      complications in 19.4%, and incisional hernias in 9.1%. In the control group the
      incidence of HAT was 5.8% (P = 0.004), biliary complications 18.5% (P = NS) and
      incisional hernias 7.2% (P = NS). Patients on SRL experienced significantly
      higher levels of serum triglycerides but fewer acute cellular rejections. Bone
      marrow and renal functions were similar in both the groups. Our findings would
      suggest that SRL is safe and effective for very selected OLT recipients.
      Randomized controlled trials are necessary to confirm our results.

PMID- 19765267
TI  - Evaluation of the analytical performances of a portable, 18-parameter hemometric
      system using capillary blood samples for blood donor enrolment.
AB  - BACKGROUND AND OBJECTIVES: Blood donor enrolment process is frequently based on
      the sole capillary haemoglobin (Hb) evaluation while platelet donors by apheresis
      also requires platelet (Plt) count. The 'sole Hb' approach prevents a complete
      donor evaluation and does not allow Plt donor enrolment. To extend blood counts
      before donations, we evaluated the performances of a multiparametric counter
      using capillary blood. MATERIALS AND METHODS: The ABX Micros 60 (Micros 60) blood
      analyzer was employed on capillary blood and compared with venous counts by a
      reference counter (Coulter AcT 5diff) in a first series of 416 donors and in a
      second series of 136, after a 3-month period of routine use of this study
      counter. An average of 50 microl of capillary blood was collected whose 10 microl
      had been aspirated by Micros 60. RESULTS: High correlations were found between
      capillary counts using Micros 60 and venous counts using the reference counter.
      Mean Plt counts differed of 37 x 10(9)/l less for capillary approach in the first
      series of comparisons, but decreased to 10 x 10(9)/l less in the second series
      due to a greater expertise of operators in capillary sampling. All other
      parameters were accurate and never reached clinical relevance albeit they showed
      statistically significant differences. CONCLUSION: Data on Micros 60 demonstrated
      that capillary predonation counts may represent a feasible and effective approach
      to realize an accurate enrolment process of blood and Plt donors.

PMID- 19765268
TI  - Factors influencing confidential unit exclusions in blood donors.
AB  - BACKGROUND AND OBJECTIVE: In many countries blood donors can exclude their
      donated blood from being transfused in a confidential unit exclusion (CUE)
      process. We aimed to identify characteristics which might influence the decision
      for CUE. STUDY DESIGN AND METHODS: In a 3-step approach we first enrolled 29
      German blood donation centers in 2005 and addressed how the clarity of different
      CUE forms applied in these centers was rated by first time blood donors and also
      assessed three newly designed CUE forms. Second, we performed a survey on the
      characteristics of the CUE process including 25 centers. Third, we performed an
      intervention study, in which the CUE form originally applied in the study centre
      was compared with a newly developed CUE form in a before-after study design with
      respect to the corresponding CUE rates. RESULTS: (1) Clarity of the CUE forms
      varied considerably. (2) The CUE rate was higher (P < 0.05) when nurses rather
      than a physician were involved in informing the donors and when the CUE form was
      submitted anonymously instead of being handed to a person. (3) Application of the
      newly designed CUE form which was rated as being very clear resulted in a 31%
      decrease in the CUE rate. CONCLUSIONS: Design of the CUE form and characteristics
      of the CUE process may considerably influence the CUE rates.

PMID- 19765269
TI  - Discussion on the use of taxanes for treatment of breast cancers in BRCA1
      mutations carriers.

PMID- 19765270
TI  - Evaluation of a multiple ecological level child obesity prevention program:
      Switch what you Do, View, and Chew.
AB  - BACKGROUND: Schools are the most frequent target for intervention programs aimed
      at preventing child obesity; however, the overall effectiveness of these programs
      has been limited. It has therefore been recommended that interventions target
      multiple ecological levels (community, family, school and individual) to have
      greater success in changing risk behaviors for obesity. This study examined the
      immediate and short-term, sustained effects of the Switch program, which targeted
      three behaviors (decreasing children's screen time, increasing fruit and
      vegetable consumption, and increasing physical activity) at three ecological
      levels (the family, school, and community). METHODS: Participants were 1,323
      children and their parents from 10 schools in two states. Schools were matched
      and randomly assigned to treatment and control. Measures of the key behaviors and
      body mass index were collected at baseline, immediately post-intervention, and 6
      months post-intervention. RESULTS: The effect sizes of the differences between
      treatment and control groups ranged between small (Cohen's d = 0.15 for body mass
      index at 6 months post-intervention) to large (1.38; parent report of screen time
      at 6 months post-intervention), controlling for baseline levels. There was a
      significant difference in parent-reported screen time at post-intervention in the
      experimental group, and this effect was maintained at 6 months post-intervention
      (a difference of about 2 hours/week). The experimental group also showed a
      significant increase in parent-reported fruit and vegetable consumption while
      child-reported fruit and vegetable consumption was marginally significant. At the
      6-month follow-up, parent-reported screen time was significantly lower, and
      parent and child-reported fruit and vegetable consumption was significantly
      increased. There were no significant effects on pedometer measures of physical
      activity or body mass index in the experimental group. The intervention effects
      were moderated by child sex (for fruit and vegetable consumption, physical
      activity, and weight status), family involvement (for fruit and vegetable
      consumption), and child body mass index (for screen time). The perception of
      change among the experimental group was generally positive with 23% to 62%
      indicating positive changes in behaviors. CONCLUSION: The results indicate that
      the Switch program yielded small-to-modest treatment effects for promoting
      children's fruit and vegetable consumption and minimizing screen time. The Switch
      program offers promise for use in youth obesity prevention.

PMID- 19765271
TI  - Brazilian Network for HIV Drug Resistance Surveillance: a survey of individuals
      recently diagnosed with HIV.
AB  - Use of antiretrovirals is widespread in Brazil, where more than 200,000
      individuals are under treatment. Although general prevalence of primary
      antiretroviral resistance in Brazil is low, systematic sampling in large
      metropolitan areas has not being performed.The HIV Threshold Survey methodology
      (HIV-THS, WHO) was utilized, targeting Brazil's four major regions and selecting
      the six most populated state capitals: Sao Paulo, Rio de Janeiro, Salvador, Porto
      Alegre, Brasilia and Belem. We were able to sequence samples from 210 individuals
      with recent HIV diagnosis, 17 of them (8.1%) carrying HIV isolates with primary
      antiretroviral resistance mutations. Five, nine and four isolates showed
      mutations related to resistance to nucleoside reverse transcriptase inhibitors
      (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease
      inhibitors (PIs), respectively. Using HIV-THS, we could find an intermediate
      level of transmitted resistance (5% to 15%) in Belem/Brasilia, Sao Paulo and Rio
      de Janeiro. Lower level of transmitted resistance (<5%) were observed in the
      other areas. Despite the extensive antiretroviral exposure and high rates of
      virologic antiretroviral failure in Brazil, the general prevalence of primary
      resistance is still low. However, an intermediate level of primary resistance was
      found in the four major Brazilian cities, confirming the critical need to start
      larger sampling surveys to better define the risk factors associated with
      transmission of resistant HIV.

PMID- 19765272
TI  - Use of in vivo-induced antigen technology (IVIAT) for the identification of
      Streptococcus suis serotype 2 in vivo-induced bacterial protein antigens.
AB  - BACKGROUND: Streptococcus suis serotype 2 (SS2) is a zoonotic agent that causes
      death and disease in both humans and swine. A better understanding of SS2-host
      molecular interactions is crucial for understanding SS2 pathogenesis and
      immunology. Conventional genetic and biochemical approaches used to study SS2
      virulence factors are unable to take into account the complex and dynamic
      environmental stimuli associated with the infection process. In this study, in
      vivo-induced antigen technology (IVIAT), an immunoscreening technique, was used
      to identify the immunogenic bacterial proteins that are induced or upregulated in
      vivo during SS2 infection. RESULTS: Convalescent-phase sera from pigs infected
      with SS2 were pooled, adsorbed against in vitro antigens, and used to screen SS2
      genomic expression libraries. Upon analysis of the identified proteins, we were
      able to assign a putative function to 40 of the 48 proteins. These included
      proteins implicated in cell envelope structure, regulation, molecule synthesis,
      substance and energy metabolism, transport, translation, and those with unknown
      functions. The in vivo-induced changes in the expression of 10 of these 40 genes
      were measured using real-time reverse transcription (RT)-PCR, revealing that the
      expression of 6 of the 10 genes was upregulated in the in vivo condition. The
      strain distribution of these 10 genes was analyzed by PCR, and they were found in
      the most virulent SS2 strains. In addition, protein sequence alignments of the
      newly identified proteins demonstrate that three are putative virulence
      associated proteins. CONCLUSION: Collectively, our results suggest that these in
      vivo-induced or upregulated genes may contribute to SS2 disease development. We
      hypothesize that the identification of factors specifically induced or
      upregulated during SS2 infection will aid in our understanding of SS2
      pathogenesis and may contribute to the control SS2 outbreaks. In addition, the
      proteins identified using IVIAT may be useful potential vaccine candidates or
      virulence markers.

PMID- 19765273
TI  - Ethanol inhibits LPS-induced signaling and modulates cytokine production in
      peritoneal macrophages in vivo in a model for binge drinking.
AB  - BACKGROUND: Previous reports indicate that ethanol, in a binge drinking model in
      mice, inhibits the production of pro-inflammatory cytokines in vivo. However, the
      inhibition of signaling through TLR4 has not been investigated in this
      experimental model in vivo. Considering evidence that signaling can be very
      different in vitro and in vivo, the present study was conducted to determine if
      effects of ethanol on TLR4 signaling reported for cells in culture or cells
      removed from ethanol treated mice and stimulated in culture also occur when
      ethanol treatment and TLR4 activation occur in vivo. RESULTS: Phosphorylated p38,
      ERK, and c-Jun (nuclear) were quantified with kits or by western blot using
      samples taken 15, 30, and 60 min after stimulation of peritoneal macrophages with
      lipopolysaccharide in vivo. Effects of ethanol were assessed by administering
      ethanol by gavage at 6 g/kg 30 min before administration of lipopolysaccharide
      (LPS). Cytokine concentrations in the samples of peritoneal lavage fluid and in
      serum were determined at 1, 2, and 6 hr after lipopolysaccharide administration.
      All of these data were used to measure the area under the concentration vs time
      curve, which provided an indication of the overall effects of ethanol in this
      system. Ethanol suppressed production of most pro-inflammatory cytokines to a
      similar degree as it inhibited key TLR4 signaling events. However, NF-kappaB
      (p65) translocation to the nucleus was not inhibited by ethanol. To determine if
      NF-kappaB composed of other subunits was inhibited, transgenic mice with a
      luciferase reporter were used. This revealed a reproducible inhibition of NF
      kappaB activity, which is consistent with the observed inhibition of cytokines
      whose expression is known to be NF-kappaB dependent. CONCLUSION: Overall, the
      effects of ethanol on signalling in vivo were similar to those reported for in
      vitro exposure to ethanol and/or lipopolysaccharide. However, inhibition of the
      activation of NF-kappaB was not detected as translocation of p65 to the nucleus
      but was detected using transgenic reporter mice. The observation that ethanol
      given 24 hr before dosing with LPS modulated production of some cytokines
      indicates a persistent effect which does not require continued presence of
      ethanol.

PMID- 19765274
TI  - Misrecognition of facial expressions in delinquents.
AB  - BACKGROUND: Previous reports have suggested impairment in facial expression
      recognition in delinquents, but controversy remains with respect to how such
      recognition is impaired. To address this issue, we investigated facial expression
      recognition in delinquents in detail. METHODS: We tested 24 male adolescent/young
      adult delinquents incarcerated in correctional facilities. We compared their
      performances with those of 24 age- and gender-matched control participants. Using
      standard photographs of facial expressions illustrating six basic emotions,
      participants matched each emotional facial expression with an appropriate verbal
      label. RESULTS: Delinquents were less accurate in the recognition of facial
      expressions that conveyed disgust than were control participants. The delinquents
      misrecognized the facial expressions of disgust as anger more frequently than did
      controls. CONCLUSION: These results suggest that one of the underpinnings of
      delinquency might be impaired recognition of emotional facial expressions, with a
      specific bias toward interpreting disgusted expressions as hostile angry
      expressions.

PMID- 19765275
TI  - The nature and causes of unintended events reported at ten emergency departments.
AB  - BACKGROUND: Several studies on patient safety have shown that a substantial
      number of patients suffer from unintended harm caused by healthcare management in
      hospitals. Emergency departments (EDs) are challenging hospital settings with
      regard to patient safety. There is an increased sense of urgency to take
      effective countermeasures in order to improve patient safety. This can only be
      achieved if interventions tackle the dominant underlying causes. The objectives
      of our study are to examine the nature and causes of unintended events in EDs and
      the relationship between type of event and causal factor structure. METHODS:
      Study at EDs of 10 hospitals in the Netherlands. The study period per ED was 8 to
      14 weeks, in which staff were asked to report unintended events. Unintended
      events were broadly defined as all events, no matter how seemingly trivial or
      commonplace, that were unintended and could have harmed or did harm a patient.
      Reports were analysed with a Root Cause Analysis tool (PRISMA) by an experienced
      researcher. RESULTS: 522 unintended events were reported. Of the events 25% was
      related to cooperation with other departments and 20% to problems with
      materials/equipment. More than half of the events had consequences for the
      patient, most often resulting in inconvenience or suboptimal care. Most root
      causes were human (60%), followed by organisational (25%) and technical causes
      (11%). Nearly half of the root causes was external, i.e. attributable to other
      departments in or outside the hospital. CONCLUSION: Event reporting gives insight
      into diverse unintended events. The information on unintended events may help
      target research and interventions to increase patient safety. It seems worthwhile
      to direct interventions on the collaboration between the ED and other hospital
      departments.

PMID- 19765276
TI  - Visualizing fusion of pseudotyped HIV-1 particles in real time by live cell
      microscopy.
AB  - BACKGROUND: Most retroviruses enter their host cells by fusing the viral envelope
      with the plasma membrane. Although the protein machinery promoting fusion has
      been characterized extensively, the dynamics of the process are largely unknown.
      RESULTS: We generated human immunodeficiency virus-1 (HIV-1) particles
      pseudotyped with the envelope (Env) protein of ecotropic murine leukemia virus
      eMLV to study retrovirus entry at the plasma membrane using live-cell microscopy.
      This Env protein mediates highly efficient pH independent fusion at the cell
      surface and can be functionally tagged with a fluorescent protein. To detect
      fusion events, double labeled particles carrying one fluorophor in Env and the
      other in the matrix (MA) domain of Gag were generated and characterized. Fusion
      events were defined as loss of Env signal after virus-cell contact. Single
      particle tracking of >20,000 individual traces in two color channels recorded 28
      events of color separation, where particles lost the Env protein, with the MA
      layer remaining stable at least for a short period. Fourty-five events were
      detected where both colors were lost simultaneously. Importantly, the first type
      of event was never observed when particles were pseudotyped with a non-fusogenic
      Env. CONCLUSION: These results reveal rapid retroviral fusion at the plasma
      membrane and permit studies of the immediate post-fusion events.

PMID- 19765277
TI  - Polymorphisms of the SIPA1 gene and sporadic breast cancer susceptibility.
AB  - BACKGROUND: The novel breast cancer metastasis modulator gene signal-induced
      proliferation-associated 1 (Sipa1) underlies the breast cancer metastasis
      efficiency modifier locus Mtes 1 and has been shown to influence mammary tumour
      metastatic efficiency in the mouse, with an ectopically expressing Sipa1 cell
      line developing 1.5 to 2 fold more surface pulmonary metastases. Sipa1 encodes a
      mitogen-inducible GTPase activating (GAP) protein for members of the Ras-related
      proteins; participates in cell adhesion and modulates mitogen-induced cell cycle
      progression. Germline SIPA1 SNPs showed association with positive lymph node
      metastasis and hormonal receptor status in a Caucasian cohort. We hypothesized
      that SIPA1 may also be correlated to breast carcinoma incidence as well as
      prognosis. Therefore, this study investigated the potential relationship of SIPA1
      and human breast cancer incidence by a germline SNP genotype frequency
      association study in a case-control Caucasian cohort in Queensland, Australia.
      METHODS: The SNPs genotyped in this study were identified in a previous study and
      the genotyping assays were carried out using TaqMan SNP Genotyping Assays. The
      data were analysed with chi-square method and the Monte Carlo style CLUMP
      analysis program. RESULTS: Results indicated significance with SIPA1 SNP
      rs3741378; the CC genotype was more frequently observed in the breast cancer
      group compared to the disease-free control group, indicating the variant C allele
      was associated with increased breast cancer incidence. CONCLUSION: This
      observation indicates SNP rs3741378 as a novel potential sporadic breast cancer
      predisposition SNP. While it showed association with hormonal receptor status in
      breast cancer group in a previous pilot study, this exonic missense SNP (Ser (S)
      to Phe (F)) changes a hydrophilic residue (S) to a hydrophobic residue (F) and
      may significantly alter the protein functions of SIPA1 in breast tumourgenesis.
      SIPA1 SNPs rs931127 (5' near gene), and rs746429 (synonymous (Ala (A) to Ala
      (A)), did not show significant associations with breast cancer incidence, yet
      were associated with lymph node metastasis in the previous study. This suggests
      that SIPA1 may be involved in different stages of breast carcinogenesis and since
      this study replicates a previous study of the associated SNP, it implicates
      variants of the SIPA1 gene as playing a potential role in breast cancer.

PMID- 19765278
TI  - A study protocol to investigate the relationship between dietary fibre intake and
      fermentation, colon cell turnover, global protein acetylation and early
      carcinogenesis: the FACT study.
AB  - BACKGROUND: A number of studies, notably EPIC, have shown a descrease in
      colorectal cancer risk associated with increased fibre consumption. Whilst the
      underlying mechanisms are likely to be multifactorial, production of the short
      chain fatty-acid butyrate fro butyratye is frequently cited as a major potential
      contributor to the effect. Butyrate inhibits histone deacetylases, which work on
      a wide range of proteins over and above histones. We therefore hypothesized that
      alterations in the acetylated proteome may be associated with a cancer risk
      phenotype in the colorectal mucosa, and that such alterations are candidate
      biomarkers for effectiveness of fibre interventions in cancer prevention. METHODS
      AN DESIGN: There are two principal arms to this study: (i) a cross-sectional
      study (FACT OBS) of 90 subjects recruited from gastroenterology clinics and; (ii)
      an intervention trial in 40 subjects with an 8 week high fibre intervention. In
      both studies the principal goal is to investigate a link between fibre intake,
      SCFA production and global protein acetylation. The primary measure is level of
      faecal butyrate, which it is hoped will be elevated by moving subjects to a high
      fibre diet. Fibre intakes will be estimated in the cross-sectional group using
      the EPIC Food Frequency Questionnaire. Subsidiary measures of the effect of
      butyrate on colon mucosal function and pre-cancerous phenotype will include
      measures of apoptosis, apoptotic regulators cell cycle and cell division.
      DISCUSSION: This study will provide a new level of mechanistic data on
      alterations in the functional proteome in response to the colon microenvironment
      which may underwrite the observed cancer preventive effect of fibre. The study
      may yield novel candidate biomarkers of fibre fermentation and colon mucosal
      function. TRIAL REGISTRATION:  TRIAL REGISTRATION NUMBER: ISRCTN90852168.

PMID- 19765279
TI  - Fibroblasts from patients with Diamond-Blackfan anaemia show abnormal expression
      of genes involved in protein synthesis, amino acid metabolism and cancer.
AB  - BACKGROUND: Diamond-Blackfan anaemia (DBA) is a rare inherited red cell
      hypoplasia characterised by a defect in the maturation of erythroid progenitors
      and in some cases associated with malformations. Patients have an increased risk
      of solid tumors. Mutations have been found in several ribosomal protein (RP)
      genes, i.e RPS19, RPS24, RPS17, RPL5, RPL11, RPL35A. Studies in haematopoietic
      progenitors from patients show that haplo-insufficiency of an RP impairs rRNA
      processing and ribosome biogenesis. DBA lymphocytes show reduced protein
      synthesis and fibroblasts display abnormal rRNA processing and impaired
      proliferation. RESULTS: To evaluate the involvement of non-haematopoietic tissues
      in DBA, we have analysed global gene expression in fibroblasts from DBA patients
      compared to healthy controls. Microarray expression profiling using Affymetrix
      GeneChip Human Genome U133A 2.0 Arrays revealed that 421 genes are differentially
      expressed in DBA patient fibroblasts. These genes include a large cluster of
      ribosomal proteins and factors involved in protein synthesis and amino acid
      metabolism, as well as genes associated to cell death, cancer and tissue
      development. CONCLUSION: This analysis reports for the first time an abnormal
      gene expression profile in a non-haematopoietic cell type in DBA. These data
      support the hypothesis that DBA may be due to a defect in general or specific
      protein synthesis.

PMID- 19765280
TI  - QUARITE (quality of care, risk management and technology in obstetrics): a
      cluster-randomized trial of a multifaceted intervention to improve emergency
      obstetric care in Senegal and Mali.
AB  - BACKGROUND: Maternal and perinatal mortality are major problems for which
      progress in sub-Saharan Africa has been inadequate, even though childbirth
      services are available, even in the poorest countries. Reducing them is the aim
      of two of the main Millennium Development Goals. Many initiatives have been
      undertaken to remedy this situation, such as the Advances in Labour and Risk
      Management (ALARM) International Program, whose purpose is to improve the quality
      of obstetric services in low-income countries. However, few interventions have
      been evaluated, in this context, using rigorous methods for analyzing
      effectiveness in terms of health outcomes. The objective of this trial is to
      evaluate the effectiveness of the ALARM International Program (AIP) in reducing
      maternal mortality in referral hospitals in Senegal and Mali. Secondary goals
      include evaluation of the relationships between effectiveness and resource
      availability, service organization, medical practices, and satisfaction among
      health personnel. METHODS/DESIGN: This is an international, multi-centre,
      controlled cluster-randomized trial of a complex intervention. The intervention
      is based on the concept of evidence-based practice and on a combination of two
      approaches aimed at improving the performance of health personnel: 1) Educational
      outreach visits; and 2) the implementation of facility-based maternal death
      reviews. The unit of intervention is the public health facility equipped with a
      functional operating room. On the basis of consent provided by hospital
      authorities, 46 centres out of 49 eligible were selected in Mali and Senegal.
      Using randomization stratified by country and by level of care, 23 centres will
      be allocated to the intervention group and 23 to the control group. The
      intervention will last two years. It will be preceded by a pre-intervention one
      year period for baseline data collection. A continuous clinical data collection
      system has been set up in all participating centres. This, along with the
      inventory of resources and the satisfaction surveys administered to the health
      personnel, will allow us to measure results before, during, and after the
      intervention. The overall rate of maternal mortality measured in hospitals during
      the post-intervention period (Year 4) is the primary outcome. The evaluation will
      also include cost-effectiveness.

PMID- 19765281
TI  - Suppressive effect of secretory phospholipase A2 inhibitory peptide on
      interleukin-1beta-induced matrix metalloproteinase production in rheumatoid
      synovial fibroblasts, and its antiarthritic activity in hTNFtg mice.
AB  - INTRODUCTION: Secretory phospholipase A2 (sPLA2) and matrix metalloproteinase
      (MMP) inhibitors are potent modulators of inflammation with therapeutic
      potential, but have limited efficacy in rheumatoid arthritis (RA). The objective
      of this study was to understand the inhibitory mechanism of phospholipase
      inhibitor from python (PIP)-18 peptide in cultured synovial fibroblasts (SF), and
      to evaluate its therapeutic potential in a human tumor necrosis factor (hTNF)
      driven transgenic mouse (Tg197) model of arthritis. METHODS: Gene and protein
      expression of sPLA2-IIA, MMP-1, MMP-2, MMP-3, MMP-9, tissue inhibitor of
      metalloproteinase (TIMP)-1, and TIMP-2 were analyzed by real time PCR and ELISA
      respectively, in interleukin (IL)-1beta stimulated rheumatoid arthritis (RA) and
      osteoarthritis (OA) synovial fibroblasts cells treated with or without inhibitors
      of sPLA2 (PIP-18, LY315920) or MMPs (MMP Inhibitor II). Phosphorylation status of
      mitogen-activated protein kinase (MAPK) proteins was examined by cell-based
      ELISA. The effect of PIP-18 was compared with that of celecoxib, methotrexate,
      infliximab and antiflamin-2 in Tg197 mice after ip administration (thrice weekly
      for 5 weeks) at two doses (10, 30 mg/kg), and histologic analysis of ankle
      joints. Serum sPLA2 and cytokines (tumor necrosis factor (TNF)alpha, IL-6) were
      measured by Escherichia coli (E coli) assay and ELISA, respectively. RESULTS: PIP
      18 inhibited sPLA2-IIA production and enzymatic activity, and suppressed
      production of MMPs in IL-1beta-induced RA and OA SF cells. Treatment with PIP-18
      blocked IL-1beta-induced p38 MAPK phosphorylation and resulted in attenuation of
      sPLA2-IIA and MMP mRNA transcription in RA SF cells. The disease modifying effect
      of PIP-18 was evidenced by significant abrogation of synovitis, cartilage
      degradation and bone erosion in hTNF Tg197 mice. CONCLUSIONS: Our results
      demonstrate the benefit that can be gained from using sPLA2 inhibitory peptide
      for RA treatment, and validate PIP-18 as a potential therapeutic in a clinically
      relevant animal model of human arthritis.

PMID- 19765282
TI  - Identification and characterization of miRNAs expressed in the bovine ovary.
AB  - BACKGROUND: MicroRNAs are the major class of gene-regulating molecules playing
      diverse roles through sequence complementarity to target mRNAs at post
      transcriptional level. Tightly regulated expression and interaction of a
      multitude of genes for ovarian folliculogenesis could be regulated by these
      miRNAs. Identification of them is the first step towards understanding miRNA
      guided gene regulation in different biological functions. Despite increasing
      efforts in miRNAs identification across various species and diverse tissue types,
      little is known about bovine ovarian miRNAs. Here, we report the identification
      and characterization of miRNAs expressed in the bovine ovary through cloning,
      expression analysis and target prediction. RESULTS: The miRNA library (5'
      independent ligation cloning method), which was constructed from bovine ovary in
      this study, revealed cloning of 50 known and 24 novel miRNAs. Among all
      identified miRNAs, 38 were found to be new for bovine and were derived from 43
      distinct loci showing characteristic secondary structure. While 22 miRNAs
      precursor loci were found to be well conserved in more than one species, 16 were
      found to be bovine specific. Most of the miRNAs were cloned multiple times, in
      which let-7a, let-7b, let-7c, miR-21, miR-23b, miR-24, miR-27a, miR-126 and miR
      143 were cloned 10, 28, 13, 4, 11, 7, 6, 4 and 11 times, respectively. Expression
      analysis of all new and some annotated miRNAs in different intra-ovarian
      structures and in other multiple tissues showed that some were present
      ubiquitously while others were differentially expressed among different tissue
      types. Bta-miR-29a was localized in the follicular cells at different
      developmental stages in the cyclic ovary. Bio-informatics prediction, screening
      and Gene Ontology analysis of miRNAs targets identified several biological
      processes and pathways underlying the ovarian function. CONCLUSION: Results of
      this study suggest the presence of miRNAs in the bovine ovary, thereby elucidate
      their potential role in regulating diverse molecular and physiological pathways
      underlying the ovarian functionality. This information will give insights into
      bovine ovarian miRNAs, which can be further characterized for their role in
      follicular development and female fertility as well.

PMID- 19765283
TI  - Accurate microRNA target prediction correlates with protein repression levels.
AB  - BACKGROUND: MicroRNAs are small endogenously expressed non-coding RNA molecules
      that regulate target gene expression through translation repression or messenger
      RNA degradation. MicroRNA regulation is performed through pairing of the microRNA
      to sites in the messenger RNA of protein coding genes. Since experimental
      identification of miRNA target genes poses difficulties, computational microRNA
      target prediction is one of the key means in deciphering the role of microRNAs in
      development and disease. RESULTS: DIANA-microT 3.0 is an algorithm for microRNA
      target prediction which is based on several parameters calculated individually
      for each microRNA and combines conserved and non-conserved microRNA recognition
      elements into a final prediction score, which correlates with protein production
      fold change. Specifically, for each predicted interaction the program reports a
      signal to noise ratio and a precision score which can be used as an indication of
      the false positive rate of the prediction. CONCLUSION: Recently, several
      computational target prediction programs were benchmarked based on a set of
      microRNA target genes identified by the pSILAC method. In this assessment DIANA
      microT 3.0 was found to achieve the highest precision among the most widely used
      microRNA target prediction programs reaching approximately 66%. The DIANA-microT
      3.0 prediction results are available online in a user friendly web server at
      http://www.microrna.gr/microT.

PMID- 19765284
TI  - Phosphodiesterase-5 inhibitors have distinct effects on the hemodynamics of the
      liver.
AB  - BACKGROUND: The NO--cGMP system plays a key role in the regulation of sinusoidal
      tonus and liver blood flow with phosphodiesterase-5 (PDE-5) terminating the
      dilatory action of cGMP. We, therefore, investigated the effects of PDE-5
      inhibitors on hepatic and systemic hemodynamics in rats. METHODS: Hemodynamic
      parameters were monitored for 60 min. after intravenous injection of sildenafil
      and vardenafil [1, 10 and 100 microg/kg (sil1, sil10, sil100, var1, var10,
      var100)] in anesthetized rats. RESULTS: Cardiac output and heart rate remained
      constant. After a short dip, mean arterial blood pressure again increased.
      Systemic vascular resistance transiently decreased slightly. Changes in hepatic
      hemodynamic parameters started after few minutes and continued for at least 60
      min. Portal (var10 -31%, sil10 -34%) and hepatic arterial resistance (var10 -30%,
      sil10 -32%) decreased significantly (p < 0.05). At the same time portal venous
      (var10 +29%, sil10 +24%), hepatic arterial (var10 +34%, sil10 +48%), and hepatic
      parenchymal blood flow (var10 +15%, sil10 +15%) increased significantly (p <
      0.05). The fractional liver blood flow (total liver flow/cardiac output)
      increased significantly (var10 26%, sil10 23%). Portal pressure remained constant
      or tended to decrease. 10 microg/kg was the most effective dose for both PDE-5
      inhibitors. CONCLUSION: Low doses of phosphodiesterase-5 inhibitors have distinct
      effects on hepatic hemodynamic parameters. Their therapeutic use in portal
      hypertension should therefore be evaluated.

PMID- 19765285
TI  - Satellite-based terrestrial production efficiency modeling.
AB  - Production efficiency models (PEMs) are based on the theory of light use
      efficiency (LUE) which states that a relatively constant relationship exists
      between photosynthetic carbon uptake and radiation receipt at the canopy level.
      Challenges remain however in the application of the PEM methodology to global net
      primary productivity (NPP) monitoring. The objectives of this review are as
      follows: 1) to describe the general functioning of six PEMs (CASA; GLO-PEM; TURC;
      C-Fix; MOD17; and BEAMS) identified in the literature; 2) to review each model to
      determine potential improvements to the general PEM methodology; 3) to review the
      related literature on satellite-based gross primary productivity (GPP) and NPP
      modeling for additional possibilities for improvement; and 4) based on this
      review, propose items for coordinated research.This review noted a number of
      possibilities for improvement to the general PEM architecture - ranging from LUE
      to meteorological and satellite-based inputs. Current PEMs tend to treat the
      globe similarly in terms of physiological and meteorological factors, often
      ignoring unique regional aspects. Each of the existing PEMs has developed unique
      methods to estimate NPP and the combination of the most successful of these could
      lead to improvements. It may be beneficial to develop regional PEMs that can be
      combined under a global framework. The results of this review suggest the
      creation of a hybrid PEM could bring about a significant enhancement to the PEM
      methodology and thus terrestrial carbon flux modeling.Key items topping the PEM
      research agenda identified in this review include the following: LUE should not
      be assumed constant, but should vary by plant functional type (PFT) or
      photosynthetic pathway; evidence is mounting that PEMs should consider
      incorporating diffuse radiation; continue to pursue relationships between
      satellite-derived variables and LUE, GPP and autotrophic respiration (Ra); there
      is an urgent need for satellite-based biomass measurements to improve Ra
      estimation; and satellite-based soil moisture data could improve determination of
      soil water stress.

PMID- 19765286
TI  - Validation of ACG Case-mix for equitable resource allocation in Swedish primary
      health care.
AB  - BACKGROUND: Adequate resource allocation is an important factor to ensure equity
      in health care. Previous reimbursement models have been based on age, gender and
      socioeconomic factors. An explanatory model based on individual need of primary
      health care (PHC) has not yet been used in Sweden to allocate resources. The aim
      of this study was to examine to what extent the ACG case-mix system could explain
      concurrent costs in Swedish PHC. METHODS: Diagnoses were obtained from electronic
      PHC records of inhabitants in Blekinge County (approx. 150,000) listed with
      public PHC (approx. 120,000) for three consecutive years, 2004-2006. The
      inhabitants were then classified into six different resource utilization bands
      (RUB) using the ACG case-mix system. The mean costs for primary health care were
      calculated for each RUB and year. Using linear regression models and log-cost as
      dependent variable the adjusted R2 was calculated in the unadjusted model
      (gender) and in consecutive models where age, listing with specific PHC and RUB
      were added. In an additional model the ACG groups were added. RESULTS: Gender,
      age and listing with specific PHC explained 14.48-14.88% of the variance in
      individual costs for PHC. By also adding information on level of co-morbidity, as
      measured by the ACG case-mix system, to specific PHC the adjusted R2 increased to
      60.89-63.41%. CONCLUSION: The ACG case-mix system explains patient costs in
      primary care to a high degree. Age and gender are important explanatory factors,
      but most of the variance in concurrent patient costs was explained by the ACG
      case-mix system.

PMID- 19765287
TI  - Dynamic localisation of Ran GTPase during the cell cycle.
AB  - BACKGROUND: Ran GTPase has multiple functions during the cell division cycle,
      including nucleocytoplasmic transport, mitotic spindle assembly and nuclear
      envelope formation. The activity of Ran is determined by both its guanine
      nucleotide-bound state and its subcellular localization. RESULTS: Here, we have
      characterised the localisation and mobility of Ran coupled to green fluorescent
      protein (GFP) during the cell cycle in live human cells. Ran-GFP is nuclear
      during interphase and is dispersed throughout the cell during mitosis. GFP
      RanQ69L, a mutant locked in the GTP-bound state, is less highly concentrated in
      the nucleus and associates with nuclear pore complexes within the nuclear
      envelope. During mitosis, GFP-RanQ69L is excluded from chromosomes and localizes
      to the spindle. By contrast, GFP-RanT24N, a mutant with low affinity for
      nucleotides, interacts relatively stably with chromatin throughout the cell cycle
      and is highly concentrated on mitotic chromosomes. CONCLUSION: These results show
      that Ran interacts dynamically with chromatin, nuclear pore complexes and the
      mitotic spindle during the cell cycle. These interactions are dependent on the
      nucleotide-bound state of the protein. Our data indicate that Ran-GTP generated
      at chromatin is highly mobile and interacts dynamically with distal structures
      that are involved in nuclear transport and mitotic spindle assembly.

PMID- 19765288
TI  - Treatment of thoraco-lumbar curves in adolescent females affected by idiopathic
      scoliosis with a progressive action short brace (PASB): assessment of results
      according to the SRS committee on bracing and nonoperative management
      standardization criteria.
AB  - BACKGROUND: The effectiveness of conservative treatment of scoliosis is
      controversial. Some studies suggest that brace is effective in stopping curve
      progression, whilst others did not report such an effect.The purpose of the
      present study was to effectiveness of Progressive Action Short Brace (PASB) in
      the correction of thoraco-lumbar curves, in agreement with the Scoliosis Research
      Society (SRS) Committee on Bracing and Nonoperative Management Standardisation
      Criteria. METHODS: Fifty adolescent females (mean age 11.8 +/- 0.5 years) with
      thoraco-lumbar curve and a pre-treatment Risser score ranging from 0 to 2 have
      been enrolled. The minimum duration of follow-up was 24 months (mean: 55.4 +/-
      44.5 months). Antero-posterior radiographs were used to estimate the curve
      magnitude (CM) and the torsion of the apical vertebra (TA) at 5 time points:
      beginning of treatment (t1), one year after the beginning of treatment (t2),
      intermediate time between t1 and t4 (t3), end of weaning (t4), 2-year minimum
      follow-up from t4 (t5). Three situations were distinguished: curve correction,
      curve stabilisation and curve progression.The Kruskal Wallis and Spearman Rank
      Correlation tests have been used as statistical tests. RESULTS: CM mean value was
      29,30 +/- 5,16 SD at t1 and 14,67 +/- 7,65 SD at t5. TA was 12.70 +/- 6,14 SD at
      t1 and 8,95 +/- 5,82 at t5. The variation between measures of Cobb and Perdriolle
      degrees at t1,2,3,4,5 and between CM t5-t1 and TA t5-t1 were significantly
      different.Curve correction was accomplished in 94% of patients, whereas a curve
      stabilisation was obtained in 6% of patients. CONCLUSION: The PASB, due to its
      peculiar biomechanical action on vertebral modelling, is highly effective in
      correcting thoraco-lumbar curves.

PMID- 19765289
TI  - Evolution of breast cancer management in Ireland: a decade of change.
AB  - BACKGROUND: Over the last decade there has been a paradigm shift in the
      management of breast cancer, subsequent to revised surgical oncology guidelines
      and consensus statements which were derived in light of landmark breast cancer
      clinical trials conducted throughout the latter part of the 20th century. However
      the sheer impact of this paradigm shift upon all modalities of treatment, and the
      current trends in management of the disease, are largely unknown. We aimed to
      assess the changing practices of breast cancer management over the last decade
      within a specialist tertiary referral Breast Cancer Centre. METHODS: Comparative
      analysis of all aspects of the management of breast cancer patients, who
      presented to a tertiary referral Breast Cancer Centre in 1995/1996 and 2005/2006,
      was undertaken and measured against The European Society for Surgical Oncology
      guidelines for the surgical management of mammographically detected lesions
      [1998]. RESULTS: 613 patients' case profiles were analysed. Over the last decade
      we observed a dramatic increase in incidence of breast cancer [>100%], a move to
      less invasive diagnostic and surgical therapeutic techniques, as well as
      increased use of adjuvant therapies. We also witnessed the introduction of
      immediate breast reconstruction as part of routine practice CONCLUSION: We
      demonstrate that radical changes have occurred in the management of breast cancer
      in the last decade, in keeping with international guidelines. It remains
      incumbent upon us to continue to adapt our practice patterns in light of emerging
      knowledge and best evidence.

PMID- 19765290
TI  - Adherence to anti-tuberculosis treatment among pulmonary tuberculosis patients: a
      qualitative and quantitative study.
AB  - BACKGROUND: Tuberculosis (TB) patients have difficulty following a long-term
      treatment regimen. Efforts to improve treatment outcomes require better
      understanding of adherence as a complex behavioral issue and of the particular
      barriers to and facilitators of patient adherence. METHODS: This study was
      carried out in Jiangsu Province of China with both quantitative and qualitative
      approaches. For the quantitative study, 780 sputum-smear positive TB patients
      consecutively registered since 2006 in 13 counties (districts) were queried with
      a structured questionnaire. Patients who had missed 10% of their total prescribed
      doses of TB drugs were deemed as non-adherent. Risks for non-adherence were
      estimated by computing odds ratios (ORs) and their 95% confidence intervals (95%
      CIs) using a logistic regression model. We also invited 20 TB patients and 10
      local health workers for in-depth interviews. We then used content analysis based
      on this qualitative study to explore factors associated with non-adherence.
      RESULTS: The proportion of non-adherence among 670 patients was 12.2%. Univariate
      analysis showed that patients, who were illiterate, divorced/widowed, lacked
      health insurance and were migrants, were more likely to be non-adherent. The
      crude ORs(95%CIs) were 2.38(1.37-4.13), 2.42(1.30-4.52), 1.89(1.07-3.32) and
      1.98(1.03-3.83), respectively. The risk of non-adherence was lower among patients
      whose treatment was given under direct observation by village doctors or regular
      home visits by health workers, with ORs (95% CIs) of 0.19(0.10-0.36) and
      0.23(0.10-0.51), respectively. In multivariate analysis, factors associated with
      non-adherence included illiteracy (OR: 2.42; 95% CI: 1.25-4.67) and direct
      observation by village doctors (OR: 0.23; 95% CI: 0.11-0.45). The in-depth
      interviews indicated that financial burdens and extra medical expenditures,
      adverse drug reactions, and social stigma were additional potential factors
      accounted for non-adherence. CONCLUSION: More importance should be given to
      treatment adherence under the current TB control program. Heavy financial
      burdens, lack of social support, adverse drug reactions and personal factors are
      associated with non-adherence. Direct observation and regular home visits by
      health workers appear to reduce the risk of non-adherence. More patient-centered
      interventions and greater attention to structural barriers are needed to improve
      treatment adherence.

PMID- 19765291
TI  - Tuberculosis recurrence in smear-positive patients cured under DOTS in southern
      Ethiopia: retrospective cohort study.
AB  - BACKGROUND: Decentralization of DOTS has increased the number of cured smear
      positive tuberculosis (TB) patients. However, the rate of recurrence has
      increased mainly due to HIV infection. Recurrence rate could be taken as an
      important measure of long-term success of TB treatment. We aimed to find out the
      rate of recurrence in smear-positive patients cured under DOTS in southern
      Ethiopia. METHODS: We did a retrospective cohort study on cured smear-positive TB
      patients who were treated from 1998 to 2006. Recurrence of smear-positive TB was
      used as an outcome measure. Person-years of observation (PYO) were calculated per
      100 PYO from the date of cure to date of interview. Kaplan-Meier and Cox
      regression methods were used to determine the survival and the hazard ratio (HR).
      RESULTS: 368 cured smear-positive TB patients which were followed for 1463 person
      years. Of these, 187 patients (50.8%) were men, 277 patients (75.5%) were
      married, 157 (44.2%) were illiterate, and 152 patients (41.3%) were farmers. 15
      of 368 smear-positive patients had recurrence. The rate of recurrence was 1 per
      100 PYO (0.01 per annum). Recurrence was not associated with age, sex,
      occupation, marital status and level of education. CONCLUSION: High recurrence
      rate occurred among smear-positive patients cured under DOTS. Further studies are
      required to identify factors contributing to high recurrence rates to improve
      disease free survival of TB patients after treatment.

PMID- 19765292
TI  - The impact of population size on the evolution of asexual microbes on smooth
      versus rugged fitness landscapes.
AB  - BACKGROUND: It is commonly thought that large asexual populations evolve more
      rapidly than smaller ones, due to their increased rate of beneficial mutations.
      Less clear is how population size influences the level of fitness an asexual
      population can attain. Here, we simulate the evolution of bacteria in repeated
      serial passage experiments to explore how features such as fitness landscape
      ruggedness, the size of the mutational target under selection, and the mutation
      supply rate, interact to affect the evolution of microbial populations of
      different sizes. RESULTS: We find that if the fitness landscape has many local
      peaks, there can be a trade-off between the rate of adaptation and the potential
      to reach high fitness peaks. This result derives from the fact that whereas large
      populations evolve mostly deterministically and often become trapped on local
      fitness peaks, smaller populations can follow more stochastic evolutionary paths
      and thus locate higher fitness peaks. We also find that the target size of
      adaptation and the mutation rate interact with population size to influence the
      trade-off between rate of adaptation and final fitness. CONCLUSION: Our study
      suggests that the optimal population size for adaptation depends on the details
      of the environment and on the importance of either the ability to evolve rapidly
      or to reach high fitness levels.

PMID- 19765293
TI  - NN-align. An artificial neural network-based alignment algorithm for MHC class II
      peptide binding prediction.
AB  - BACKGROUND: The major histocompatibility complex (MHC) molecule plays a central
      role in controlling the adaptive immune response to infections. MHC class I
      molecules present peptides derived from intracellular proteins to cytotoxic T
      cells, whereas MHC class II molecules stimulate cellular and humoral immunity
      through presentation of extracellularly derived peptides to helper T cells.
      Identification of which peptides will bind a given MHC molecule is thus of great
      importance for the understanding of host-pathogen interactions, and large efforts
      have been placed in developing algorithms capable of predicting this binding
      event. RESULTS: Here, we present a novel artificial neural network-based method,
      NN-align that allows for simultaneous identification of the MHC class II binding
      core and binding affinity. NN-align is trained using a novel training algorithm
      that allows for correction of bias in the training data due to redundant binding
      core representation. Incorporation of information about the residues flanking the
      peptide-binding core is shown to significantly improve the prediction accuracy.
      The method is evaluated on a large-scale benchmark consisting of six independent
      data sets covering 14 human MHC class II alleles, and is demonstrated to
      outperform other state-of-the-art MHC class II prediction methods. CONCLUSION:
      The NN-align method is competitive with the state-of-the-art MHC class II peptide
      binding prediction algorithms. The method is publicly available at
      http://www.cbs.dtu.dk/services/NetMHCII-2.0.

PMID- 19765294
TI  - Osteopontin: an early innate immune marker of Escherichia coli mastitis harbors
      genetic polymorphisms with possible links with resistance to mastitis.
AB  - BACKGROUND: Mastitis is the most important disease in dairy cows and it causes
      significant lost of profit to producers. Identification of the genes, and their
      variants, involved in innate immune responses is essential for the understanding
      of this inflammatory disease and to identify potential genetic markers for
      resistance to mastitis. The progeny of dairy cows would benefit from receiving
      favourable alleles that support greater resistance to infection, thus reducing
      antibiotic use. This study aims to identify a key gene in the innate immune
      response to mastitis, led us to evaluate its genetic association with somatic
      cell score (SCS), which is an indicator of clinical mastitis, and to evaluate its
      impact on other traits related to milk production. RESULTS: The osteopontin
      transcript (SPP1) was identified in the somatic cells from cows experimentally
      infected with Escherichia coli. By selecting bulls with extreme estimated
      breeding values (EBVs) for SCS, which is an indicator of mammary gland health,
      four DNA polymorphisms in the SPP1 genomic sequence were found. Statistical
      analysis revealed that the SNP SPP1c.-1301G>A has an impact on EBV for SCS (P <
      0.001) Using an allele substitution model, SPP1c.-1251C>T, SPP1c.-430G>A, and
      SPP1c.*40A>C have an impact on SCS whereas SPP1c.-1301G>A has an effect on the
      EBVs for milk yield (second and third lactations), fat and protein percentages
      (all three lactations). Analysis revealed statistically significant differences
      between haplotype groups at a comparison-wise level with sire EBVS for SCS for
      the first (P = 0.012), second (P < 0.001), and third (P < 0.001) lactations.
      CONCLUSION: This study reports the link between DNA polymorphisms of SPP1, the
      number of milk immune cells and, potentially, the susceptibility to mastitis.
      These SNPs were identified by in silico search to be located in transcription
      factor recognition sites which factors are presumably involved in the Th1 immune
      response and in the Th2 regulation pathway. Indeed, one SNP abolished the SP1
      recognition site, whereas another SNP affected the transcription binding factor
      IKAROS. All together, these findings support the genetic potential of these
      variants in terms of selection for the improvement of mastitis resistance in
      dairy cows.

PMID- 19765295
TI  - Evidence-based guidelines in the evaluation of work disability: an international
      survey and a comparison of quality of development.
AB  - BACKGROUND: In social insurance, the evaluation of work disability is becoming
      stricter as priority is given to the resumption of work, which calls for a
      guarantee of quality for these evaluations. Evidence-based guidelines have become
      a major instrument in the quality control of health care, and the quality of
      these guidelines' development can be assessed using the AGREE instrument. In
      social insurance medicine, such guidelines are relatively new. We were interested
      to know what guidelines have been developed to support the medical evaluation of
      work disability and the quality of these guidelines. METHODS: Five European
      countries that were reported to use guidelines were approached, using a recent
      inventory of evaluations of work disability in Europe. We focused on guidelines
      that are disease-oriented and formally prescribed in social insurance medicine.
      Using the AGREE instrument, these guidelines were appraised by two researchers.
      We asked two experts involved in guideline development to indicate if they agreed
      with our results and to provide explanations for insufficient scores. RESULTS: We
      found six German and sixteen Dutch sets of disease-oriented guidelines in
      official use. The AGREE instrument was applicable, requiring minor adaptations.
      The appraisers reached consensus on all items. Each guideline scored well on
      'scope and purpose' and 'clarity and presentation'. The guidelines scored
      moderately on 'stakeholder involvement' in the Netherlands, but insufficiently in
      Germany, due mainly to the limited involvement of patients' representatives in
      this country. All guidelines had low scores on 'rigour of development', which was
      due partly to a lack of documentation and of existing evidence. 'Editorial
      independence' and 'applicability' had low scores in both countries as a result of
      how the production was organised. CONCLUSION: Disease-oriented guidelines in
      social insurance medicine for the evaluation of work disability are a recent
      phenomenon, so far restricted to Germany and the Netherlands. The AGREE
      instrument is suitably applicable to assess the quality of guideline development
      in social insurance medicine, but some of the scoring rules need to be adapted to
      the context of social insurance. Existing guidelines do not meet the AGREE
      criteria to a sufficient level. The way patients' representatives can be involved
      needs further discussion. The guidelines would profit from more specific
      recommendations and, for providing evidence, more research is needed on the
      functional capacity of people with disabilities.

PMID- 19765296
TI  - Response to gefitinib and erlotinib in Non-small cell lung cancer: a
      restrospective study.
AB  - BACKGROUND: In Non-small cell lung cancer (NSCLC), an overactive epidermal growth
      factor receptor (EGFR) pathway is a component of the malignant phenotype. Two
      tyrosine kinase inhibitors (TKIs) of EGFR, gefinitib and erlotinib, have been
      used with variable benefit. METHODS: We have analyzed outcome data of a
      population of NSCLC patients that received these TKIs to determine the benefit
      derived and to define the clinical and molecular parameters that correlate with
      response. Tumor tissue from a subgroup of these patients was analyzed by
      immunohistochemistry to measure the expression level of EGFR and four activated
      (phosphorylated) members of the pathway, pEGFR, pERK, pAKT, and pSTAT3. RESULTS:
      Erlotinib was slightly superior to gefitinib in all measures of response,
      although the differences were not statistically significant. The most robust
      clinical predictors of time to progression (TTP) were best response and rash (p <
      0.0001). A higher level of pEGFR was associated with longer TTP, while the total
      EGFR level was not associated with response. Higher levels of pAKT and pSTAT3
      were also associated with longer TTP. In contrast, a higher level of pERK1/2 was
      associated with shorter TTP. CONCLUSION: These observations suggest the
      hypothesis that tumor cells that have activated EGFR pathways, presumably being
      utilized for survival, are clinically relevant targets for pathway inhibition. An
      accurate molecular predictive model of TKI response should include activated
      members of the EGFR pathway. TKIs may be best reserved for tumors expressing
      pEGFR and pAKT or pSTAT, and little pERK. In the absence of molecular predictors
      of response, the appearance of a rash and a positive first scan are good clinical
      indicators of response.

PMID- 19765297
TI  - Proteomics computational analyses suggest that the bornavirus glycoprotein is a
      class III viral fusion protein (gamma penetrene).
AB  - BACKGROUND: Borna disease virus (BDV) is the type member of the Bornaviridae, a
      family of viruses that induce often fatal neurological diseases in horses, sheep
      and other animals, and have been proposed to have roles in certain psychiatric
      diseases of humans. The BDV glycoprotein (G) is an extensively glycosylated
      protein that migrates with an apparent molecular mass of 84,000 to 94,000
      kilodaltons (kDa). BDV G is post-translationally cleaved by the cellular
      subtilisin-like protease furin into two subunits, a 41 kDa amino terminal protein
      GP1 and a 43 kDa carboxyl terminal protein GP2. RESULTS: Class III viral fusion
      proteins (VFP) encoded by members of the Rhabdoviridae, Herpesviridae and
      Baculoviridae have an internal fusion domain comprised of beta sheets, other beta
      sheet domains, an extended alpha helical domain, a membrane proximal stem domain
      and a carboxyl terminal anchor. Proteomics computational analyses suggest that
      the structural/functional motifs that characterize class III VFP are located
      collinearly in BDV G. Structural models were established for BDV G based on the
      post-fusion structure of a prototypic class III VFP, vesicular stomatitis virus
      glycoprotein (VSV G). CONCLUSION: These results suggest that G encoded by members
      of the Bornavirdae are class III VFPs (gamma-penetrenes).

PMID- 19765298
TI  - Transmissibility studies of vacuolar changes in the rostral colliculus of pigs.
AB  - BACKGROUND: Histopathological examinations of brains from healthy pigs have
      revealed localised vacuolar changes, predominantly in the rostral colliculus,
      that are similar to the neuropil vacuolation featured in the transmissible
      spongiform encephalopathies and have been described in pigs challenged
      parenterally with the agent causing bovine spongiform encephalopathy (BSE).
      Feedstuff containing BSE-contaminated meat and bone meal (MBM) may have been fed
      to pigs prior to the ban of mammalian MBM in feed of farmed livestock in the
      United Kingdom in 1996, but there is no evidence of the natural occurrence of a
      transmissible spongiform encephalopathy (TSE) in the domestic pig. Furthermore,
      experimental transmission of BSE to pigs by the oral route has been unsuccessful.
      A study was conducted to investigate whether the localised vacuolar changes in
      the porcine brain were associated with a transmissible aetiology and therefore
      biologically significant. Two groups of ten pigs were inoculated parenterally
      with vacuolated rostral colliculus from healthy pigs either born before 1996 or
      born after 1996. Controls included ten pigs similarly inoculated with rostral
      colliculus from New Zealand-derived pigs and nine pigs inoculated with a bovine
      BSE brain homogenate. RESULTS: None of the pigs inoculated with rostral
      colliculus developed a TSE-like neurological disease up to five years post
      inoculation when the study was terminated, and disease-associated prion protein,
      PrPd, was not detected in the brains of these pigs. By contrast, eight of nine
      BSE-inoculated pigs developed neurological signs, two of which had detectable
      PrPd by postmortem tests. No significant histopathological changes were detected
      to account for the clinical signs in the PrPd-negative, BSE-inoculated pigs.
      CONCLUSION: The findings in this study suggest that vacuolation in the porcine
      rostral colliculus is not caused by a transmissible agent and is probably a
      clinically insignificant change. The presence of neurological signs in pigs
      inoculated with BSE without detectable PrPd raises the possibility that the BSE
      agent may produce a prion disease in pigs that remains undetected by the current
      postmortem tests.

PMID- 19765299
TI  - Ending intimate partner violence after pregnancy: findings from a community-based
      longitudinal study in Nicaragua.
AB  - BACKGROUND: Although reducing intimate partner violence (IPV) is a pervasive
      public health problem, few longitudinal studies in developing countries have
      assessed ways to end such abuse. To this end, this paper aims to analyze
      individual, family, community and societal factors that facilitate reducing IPV.
      METHODS: A longitudinal population-based study was conducted in Leon, Nicaragua
      at a demographic surveillance site. Women (n = 478) who were pregnant between
      2002 and 2003 were interviewed, and 398 were found at follow-up, 2007. Partner
      abuse was measured using the WHO Multi-country study on women's health and
      domestic violence questionnaire. Women's socio demographic variables, perceived
      emotional distress, partner control, social resources, women's norms and
      attitudes towards IPV and help-seeking behaviours were also assessed. Ending of
      abuse was defined as having experienced any abuse in a lifetime or during
      pregnancy but not at follow-up. Crude and adjusted odds ratios were applied.
      RESULTS: Of the women exposed to lifetime or pregnancy IPV, 59% reported that
      their abuse ended. This finding took place in a context of a substantial shift in
      women's normative attitudes towards not tolerating abuse. At the family level, no
      or diminishing partner control [ORadj 6.7 (95%CI 3.5-13)] was associated with
      ending of abuse. At the societal level, high or improved social resources [ORadj
      2.0 (95%CI 1.1.-3.7)] were also associated with the end of abuse. CONCLUSION: A
      considerable proportion of women reported end of violence. This might be related
      to a favourable change in women's norms and attitudes toward gender roles and
      violence and a more positive attitude towards interventions from people outside
      their family to end abuse. Maintaining and improving social resources and
      decreasing partner control and isolation are key interventions to ending abuse.
      Abuse inquiring may also play an important role in this process and must include
      health care provider's training and a referral system to be more effective.
      Interventions at the community level are crucial to reducing partner violence.

PMID- 19765300
TI  - A cell surface interaction network of neural leucine-rich repeat receptors.
AB  - BACKGROUND: The vast number of precise intercellular connections within
      vertebrate nervous systems is only partly explained by the comparatively few
      known extracellular guidance cues. Large families of neural orphan receptor
      proteins have been identified and are likely to contribute to these recognition
      processes but due to the technical difficulty in identifying novel extracellular
      interactions of membrane-embedded proteins, their ligands remain unknown.
      RESULTS: To identify novel neural recognition signals, we performed a large
      systematic protein interaction screen using an assay capable of detecting low
      affinity extracellular protein interactions between the ectodomains of 150
      zebrafish receptor proteins containing leucine-rich-repeat and/or immunoglobulin
      superfamily domains. We screened 7,592 interactions to construct a network of 34
      cell surface receptor-ligand pairs that included orphan receptor subfamilies such
      as the Lrrtms, Lrrns and Elfns but also novel ligands for known receptors such as
      Robos and Unc5b. A quantitative biochemical analysis of a subnetwork involving
      the Unc5b and three Flrt receptors revealed a surprising quantitative variation
      in receptor binding strengths. Paired spatiotemporal gene expression patterns
      revealed dynamic neural receptor recognition maps within the developing nervous
      system, providing biological support for the network and revealing likely
      functions. CONCLUSIONS: This integrated interaction and expression network
      provides a rich source of novel neural recognition pathways and highlights the
      importance of quantitative systematic extracellular protein interaction screens
      to mechanistically explain neural wiring patterns.

PMID- 19765301
TI  - Longevity and relationships with children: the importance of the parental role.
AB  - BACKGROUND: Social networks predict longevity across societies but specific
      mechanisms are largely unknown. The aim of this work was to examine the role of
      children in the longevity of elderly men and women in a cohort of community
      dwelling elderly people in Spain. METHODS: The data were taken from the "Aging in
      Leganes" cohort study with 15 years of follow-up. The baseline population was an
      age- and sex-stratified random sample of community dwelling people over 65 living
      in Leganes (Madrid) in 1993. Poor relationship with at least one child, emotional
      support and the perceived roles elders play in the lives of their children,
      extended family, spouse and friends were assessed at baseline. Cox proportional
      hazards models were fit to investigate the effects of social roles variables on
      longevity, adjusting for a wide range of socioeconomic, behavioural and health
      covariates. RESULTS: In the fully adjusted model, having a poor relationship with
      at least one child increased mortality by 30%. Elderly persons who felt their
      role in their children's lives was important (HR = 0.70; 95% CI 0.54; 0.91) had a
      lower mortality risk than those who felt they played a small role. Feeling loved
      and listened to by one's children did not have an effect on survival. Maintaining
      an important role in the extended family was also significantly associated with
      survival. CONCLUSION: In this Mediterranean population, maintaining an important
      role in the lives of one's children is associated with survival. Functions of
      social networks related to meaning of life and different forms of social support
      may have important effects on mortality, and these functions may vary across
      cultures according to family norms and values.

PMID- 19765302
TI  - A combination of transposable elements and magnetic cell sorting provides a very
      efficient transgenesis system for chicken primary erythroid progenitors.
AB  - BACKGROUND: Stable transgenesis is an undeniable key to understanding any genetic
      system. Retrovirus-based insertional strategies, which feature several technical
      challenges when they are used, are often limited to one particular species, and
      even sometimes to a particular cell type as the infection depends on certain
      cellular receptors. A universal-like system, which would allow both stable
      transgene expression independent of the cell type and an efficient sorting of
      transfected cells, is required when handling cellular models that are
      incompatible with retroviral strategies. RESULTS: We report here on the
      combination of a stable insertional transgenesis technique, based on the Tol2
      transposon system together with the magnetic cell sorting (MACS) technique, which
      allows specific selection of cells carrying the transgene in an efficient,
      reliable and rapid way. CONCLUSION: This new Tol2/MACS system leads to stable
      expression in a culture of primary chicken erythroid cells highly enriched in
      cells expressing the transgene of interest. This system could be used in a wide
      variety of vertebrate species.

PMID- 19765303
TI  - Overexpression of leptin receptor predicts an unfavorable outcome in Middle
      Eastern ovarian cancer.
AB  - BACKGROUND: Recent epidemiological studies have suggested that obesity is
      associated with ovarian cancer. Obesity hormone leptin and its receptor (Ob-R)
      contribute to tumor development by enhancing cell growth and survival. This study
      was design to investigate the prevalence of leptin and Ob-R in Middle Eastern
      epithelial ovarian cancer (EOC) and to analyze the role of leptin and the
      mechanisms under its action in EOC tissue sample and cell lines. METHODS: The
      expression of leptin and Ob-R was examined by immunohistochemistry in a tissue
      microarray of 156 EOC samples. Proliferation of EOC cells in response to leptin
      was assessed by MTT assays, and its anti-apoptotic effects were determined by
      flow cytometry. Effect of leptin on PI3K/AKT signaling pathway was further
      determined by western blotting. RESULTS: In clinical samples, Ob-R overexpression
      was seen in 59.2% EOCs and was significantly associated with poor progression
      free survival (p = 0.0032). Furthermore, Ob-R expression was associated with anti
      apoptotic proteins Bcl-XL (p = 0.0035) and XIAP (p = 0.0001). In vitro analysis
      using EOC cell lines showed that leptin stimulated cell proliferation and
      inhibits apoptosis via activation of PI3K/AKT signaling pathway. Inhibition of
      PI3K activity by LY294002, a specific inhibitor of PI3-kinase abrogated leptin
      mediated PI3K/AKT signaling. Gene silencing of Ob-R with Ob-R siRNA in EOC cells
      resulted in down regulation of phospho-AKT and its down stream targets.
      CONCLUSION: Our findings have potential clinical implication for EOC development
      and progression.

PMID- 19765304
TI  - Determining a cost effective intervention response to HIV/AIDS in Peru.
AB  - BACKGROUND: The HIV epidemic in Peru is still regarded as concentrated --
      sentinel surveillance data shows greatest rates of infection in men who have sex
      with men, while much lower rates are found in female sex workers and still lower
      in the general population. Without an appropriate set of preventive
      interventions, continuing infections could present a challenge to the
      sustainability of the present programme of universal access to treatment.
      Determining how specific prevention and care strategies would impact on the
      health of Peruvians should be key in reshaping the national response. METHODS:
      HIV/AIDS prevalence levels for risk groups with sufficient sentinel survey data
      were estimated. Unit costs were calculated for a series of interventions against
      HIV/AIDS which were subsequently inputted into a model to assess their ability to
      reduce infection transmission rates. Interventions included: mass media,
      voluntary counselling and testing; peer counselling for female sex workers; peer
      counselling for men who have sex with men; peer education of youth in-school;
      condom provision; STI treatment; prevention of mother to child transmission; and
      highly active antiretroviral therapy. Impact was assessed by the ability to
      reduce rates of transmission and quantified in terms of cost per DALY averted.
      RESULTS: Results of the analysis show that in Peru, the highest levels of HIV
      prevalence are found in men who have sex with men. Cost effectiveness varied
      greatly between interventions ranging from peer education of female commercial
      sex workers at $US 55 up to $US 5,928 (per DALY averted) for prevention of mother
      to child transmission. CONCLUSION: The results of this work add evidence-based
      clarity as to which interventions warrant greatest consideration when planning an
      intervention response to HIV in Peru. Cost effectiveness analysis provides a
      necessary element of transparency when facing choices about priority setting,
      particularly when the country plans to amplify its response through new
      interventions partly funded by the GFATM.

PMID- 19765305
TI  - The Sam domain of the lipid phosphatase Ship2 adopts a common model to interact
      with Arap3-Sam and EphA2-Sam.
AB  - BACKGROUND: Sterile alpha motif (Sam) domains are small protein modules that can
      be involved in homotypic or heterotypic associations and exhibit different
      functions. Previous studies have demonstrated that the Sam domain of the lipid
      phosphatase Ship2 can hetero-dimerize with the Sam domain of the PI3K effector
      protein Arap3. RESULTS: Here, we determine the NMR solution structure of Arap3
      Sam and implement a multidisciplinary approach consisting of NMR spectroscopy,
      ITC (Isothermal Titration Calorimetry), mutagenesis and molecular modeling
      studies to analyze the interaction between Ship2-Sam and Arap3-Sam. This work
      reveals that Arap3-Sam may associate with Ship2-Sam by adopting a binding mode
      common to other Sam domains. This binding mode is identical to what we have very
      recently observed for the association between Ship2-Sam and the Sam domain from
      the Ephrin A2 receptor. CONCLUSION: Our studies further clarify the structural
      features that are relevant for Sam-Sam interactions involving Ship2 and give
      additional hints that could be used for the identification of new molecules able
      to selectively inhibit Sam-Sam associations.

PMID- 19765306
TI  - Finding local communities in protein networks.
AB  - BACKGROUND: Protein-protein interactions (PPIs) play fundamental roles in nearly
      all biological processes, and provide major insights into the inner workings of
      cells. A vast amount of PPI data for various organisms is available from BioGRID
      and other sources. The identification of communities in PPI networks is of great
      interest because they often reveal previously unknown functional ties between
      proteins. A large number of global clustering algorithms have been applied to
      protein networks, where the entire network is partitioned into clusters. Here we
      take a different approach by looking for local communities in PPI networks.
      RESULTS: We develop a tool, named Local Protein Community Finder, which quickly
      finds a community close to a queried protein in any network available from
      BioGRID or specified by the user. Our tool uses two new local clustering
      algorithms Nibble and PageRank-Nibble, which look for a good cluster among the
      most popular destinations of a short random walk from the queried vertex. The
      quality of a cluster is determined by proportion of outgoing edges, known as
      conductance, which is a relative measure particularly useful in undersampled
      networks. We show that the two local clustering algorithms find communities that
      not only form excellent clusters, but are also likely to be biologically relevant
      functional components. We compare the performance of Nibble and PageRank-Nibble
      to other popular and effective graph partitioning algorithms, and show that they
      find better clusters in the graph. Moreover, Nibble and PageRank-Nibble find
      communities that are more functionally coherent. CONCLUSION: The Local Protein
      Community Finder, accessible at http://xialab.bu.edu/resources/lpcf, allows the
      user to quickly find a high-quality community close to a queried protein in any
      network available from BioGRID or specified by the user. We show that the
      communities found by our tool form good clusters and are functionally coherent,
      making our application useful for biologists who wish to investigate functional
      modules that a particular protein is a part of.

PMID- 19765307
TI  - Proliferative and anti-proliferative effects of dietary levels of phytoestrogens
      in rat pituitary GH3/B6/F10 cells - the involvement of rapidly activated kinases
      and caspases.
AB  - BACKGROUND: Phytoestogens are a group of lipophillic plant compounds that can
      have estrogenic effects in animals; both tumorigenic and anti-tumorigenic effects
      have been reported. Prolactin-secreting adenomas are the most prevalent form of
      pituitary tumors in humans and have been linked to estrogen exposures. We
      examined the proliferative effects of phytoestrogens on a rat pituitary tumor
      cell line, GH3/B6/F10, originally subcloned from GH3 cells based on its ability
      to express high levels of the membrane estrogen receptor-alpha. METHODS: We
      measured the proliferative effects of these phytoestrogens using crystal violet
      staining, the activation of several mitogen-activated protein kinases (MAPKs) and
      their downstream targets via a quantitative plate immunoassay, and caspase
      enzymatic activities. RESULTS: Four phytoestrogens (coumestrol, daidzein,
      genistein, and trans-resveratrol) were studied over wide concentration ranges.
      Except trans-resveratrol, all phytoestrogens increased GH3/B6/F10 cell
      proliferation at some concentration relevant to dietary levels. All four
      phytoestrogens attenuated the proliferative effects of estradiol when
      administered simultaneously. All phytoestrogens elicited MAPK and downstream
      target activations, but with time course patterns that often differed from that
      of estradiol and each other. Using selective antagonists, we determined that
      MAPKs play a role in the ability of these phytoestrogens to elicit these
      responses. In addition, except for trans-resveratrol, a serum removal-induced
      extrinsic apoptotic pathway was blocked by these phytoestrogens. CONCLUSION:
      Phytoestrogens can block physiological estrogen-induced tumor cell growth in
      vitro and can also stimulate growth at high dietary concentrations in the absence
      of endogenous estrogens; these actions are correlated with slightly different
      signaling response patterns. Consumption of these compounds should be considered
      in strategies to control endocrine tumor cell growth, such as in the pituitary.

PMID- 19765308
TI  - Why do we put cervical collars on conscious trauma patients?
AB  - In this commentary we argue that fully alert, stable and co-operative trauma
      patients do not require the application of a semi-rigid cervical collar, even if
      they are suspected of underlying cervical spine fracture, unless their conscious
      level deteriorates or they find the short-term support of a cervical collar
      helpful. Despite the historical and cultural barriers that exist, the potential
      benefits are such that this hypothesis merits rigorous testing in well-designed
      research trials.

PMID- 19765309
TI  - Colorectal cancer prevention for low-income, sociodemographically-diverse adults
      in public housing: baseline findings of a randomized controlled trial.
AB  - BACKGROUND: This paper presents the study design, intervention components, and
      baseline data from Open Doors to Health, a study designed to address social
      contextual factors in colorectal cancer (CRC) prevention for low-income,
      racial/ethnic minority populations. METHODS: A cluster randomized design with 12
      housing sites as the primary sampling units was used: 6 sites were assigned to a
      "Peer-led plus Screening Access" (PL) condition, and 6 were assigned to
      "Screening Access only" (SCR) condition. Study-related outcomes were CRC
      screening, physical activity (measured as mean steps/day), and multivitamin use.
      RESULTS: At baseline (unweighted sample size = 1554), two-thirds self-reported
      that they were current with screening recommendations for CRC (corrected for
      medical records validation, prevalence was 52%), with half having received a
      colonoscopy (54%); 96% had health insurance. Mean steps per day was 5648 (se mean
      = 224), and on average 28% of the sample reported regular multivitamin use.
      Residents reported high levels of social support [mean = 4.40 (se = .03)] and
      moderately extensive social networks [mean = 2.66 (se = .02)]. CONCLUSION: Few
      studies have conducted community-based studies in public housing communities;
      these data suggest areas for improvement and future opportunities for
      intervention development and dissemination. Findings from the randomized trial
      will determine the effectiveness of the intervention on our health-related
      outcomes as well as inform future avenues of research.

PMID- 19765310
TI  - Intestinal parasitic infections in relation to HIV/AIDS status, diarrhea and CD4
      T-cell count.
AB  - BACKGROUND: HIV infection has been modifying both the epidemiology and outcome of
      parasitic infections. Hence, this study was undertaken to determine the
      prevalence of intestinal parasitic infection among people with and without HIV
      infection and its association with diarrhea and CD4 T-cell count. METHODS: A
      cross-sectional study was conducted at Hawassa Teaching and Referral Hospital
      focusing on HIV positive individuals, who gave blood for CD4 T-cell count at
      their first enrollment and clients tested HIV negative from November, 2008 to
      March, 2009. Data on socio-demographic factors and diarrhea status were obtained
      by interviewing 378 consecutive participants (214 HIV positive and 164 HIV
      negative). Stool samples were collected from all study subjects and examined for
      parasites using direct, formol-ether and modified acid fast stain techniques.
      RESULTS: The prevalence of any intestinal parasitic infection was significantly
      higher among HIV positive participants. Specifically, rate of infection with
      Cryptosporidium, I. belli, and S. stercoralis were higher, particularly in those
      with CD4 count less than 200 cells/microL. Diarrhea was more frequent also at the
      same lower CD4 T-cell counts. CONCLUSION: Immunodeficiency increased the risk of
      having opportunistic parasites and diarrhea. Therefore; raising patient immune
      status and screening at least for those treatable parasites is important.

PMID- 19765311
TI  - PhyloPattern: regular expressions to identify complex patterns in phylogenetic
      trees.
AB  - BACKGROUND: To effectively apply evolutionary concepts in genome-scale studies,
      large numbers of phylogenetic trees have to be automatically analysed, at a level
      approaching human expertise. Complex architectures must be recognized within the
      trees, so that associated information can be extracted. RESULTS: Here, we present
      a new software library, PhyloPattern, for automating tree manipulations and
      analysis. PhyloPattern includes three main modules, which address essential tasks
      in high-throughput phylogenetic tree analysis: node annotation, pattern matching,
      and tree comparison. PhyloPattern thus allows the programmer to focus on: i) the
      use of predefined or user defined annotation functions to perform immediate or
      deferred evaluation of node properties, ii) the search for user-defined patterns
      in large phylogenetic trees, iii) the pairwise comparison of trees by dynamically
      generating patterns from one tree and applying them to the other. CONCLUSION:
      PhyloPattern greatly simplifies and accelerates the work of the computer
      scientist in the evolutionary biology field. The library has been used to
      automatically identify phylogenetic evidence for domain shuffling or gene loss
      events in the evolutionary histories of protein sequences. However any workflow
      that relies on phylogenetic tree analysis, could be automated with PhyloPattern.

PMID- 19765312
TI  - Introduction of a qualitative perinatal audit at Muhimbili National Hospital, Dar
      es Salaam, Tanzania.
AB  - BACKGROUND: Perinatal death is a devastating experience for the mother and of
      concern in clinical practice. Regular perinatal audit may identify suboptimal
      care related to perinatal deaths and thus appropriate measures for its reduction.
      The aim of this study was to perform a qualitative perinatal audit of intrapartum
      and early neonatal deaths and propose means of reducing the perinatal mortality
      rate (PMR). METHODS: From 1st August, 2007 to 31st December, 2007 we conducted an
      audit of perinatal deaths (n = 133) with birth weight 1500 g or more at Muhimbili
      National Hospital (MNH). The audit was done by three obstetricians, two external
      and one internal auditors. Each auditor independently evaluated the cases
      narratives. Suboptimal factors were identified in the antepartum, intrapartum and
      early neonatal period and classified into three levels of delay (community,
      infrastructure and health care). The contribution of each suboptimal factor to
      adverse perinatal outcome was identified and the case graded according to
      possible avoidability. Degree of agreement between auditors was assessed by the
      kappa coefficient. RESULTS: The PMR was 92 per 1000 total births. Suboptimal
      factors were identified in 80% of audited cases and half of suboptimal factors
      were found to be the likely cause of adverse perinatal outcome and were
      preventable. Poor foetal heart monitoring during labour was indirectly associated
      with over 40% of perinatal death. There was a poor to fair agreement between
      external and internal auditors. CONCLUSION: There are significant areas of care
      that need improvement. Poor monitoring during labour was a major cause of
      avoidable perinatal mortality. This type of audit was a good starting point for
      quality assurance at MNH. Regular perinatal audits to identify avoidable causes
      of perinatal deaths with feed back to the staff may be a useful strategy to
      reduce perinatal mortality.

PMID- 19765314
TI  - Exploring protein structural dissimilarity to facilitate structure
      classification.
AB  - BACKGROUND: Classification of newly resolved protein structures is important in
      understanding their architectural, evolutionary and functional relatedness to
      known protein structures. Among various efforts to improve the database of
      Structural Classification of Proteins (SCOP), automation has received particular
      attention. Herein, we predict the deepest SCOP structural level that an
      unclassified protein shares with classified proteins with an equal number of
      secondary structure elements (SSEs). RESULTS: We compute a coefficient of
      dissimilarity (Omega) between proteins, based on structural and sequence-based
      descriptors characterising the respective constituent SSEs. For a set of 1,661
      pairs of proteins with sequence identity up to 35%, the performance of Omega in
      predicting shared Class, Fold and Super-family levels is comparable to that of
      DaliLite Z score and shows a greater than four-fold increase in the true positive
      rate (TPR) for proteins sharing the Family level. On a larger set of 600 domains
      representing 200 families, the performance of Z score improves in predicting a
      shared Family, but still only achieves about half of the TPR of Omega. The TPR
      for structures sharing a Super-family is lower than in the first dataset, but
      Omega performs slightly better than Z score. Overall, the sensitivity of Omega in
      predicting common Fold level is higher than that of the DaliLite Z score.
      CONCLUSION: Classification to a deeper level in the hierarchy is specific and
      difficult. So the efficiency of Omega may be attractive to the curators and the
      end-users of SCOP. We suggest Omega may be a better measure for structure
      classification than the DaliLite Z score, with the caveat that currently we are
      restricted to comparing structures with equal number of SSEs.

PMID- 19765315
TI  - Clinical presentation and aetiologies of acute or complicated headache among HIV
      seropositive patients in a Ugandan clinic.
AB  - BACKGROUND: We set out to define the relative prevalence and common presentations
      of the various aetiologies of headache within an ambulant HIV-seropositive adult
      population in Kampala, Uganda. METHODS: We conducted a prospective study of adult
      HIV-1-seropositive ambulatory patients consecutively presenting with new onset
      headaches. Patients were classified as focal-febrile, focal-afebrile, non-focal
      febrile or non-focal-afebrile, depending on presence or absence of fever and
      localizing neurological signs. Further management followed along a pre-defined
      diagnostic algorithm to an endpoint of a diagnosis. We assessed outcomes during
      four months of follow up. RESULTS: One hundred and eighty patients were enrolled
      (72% women). Most subjects presented at WHO clinical stages III and IV of HIV
      disease, with a median Karnofsky performance rating of 70% (IQR 60-80).The most
      common diagnoses were cryptococcal meningitis (28%, n = 50) and bacterial
      sinusitis (31%, n = 56). Less frequent diagnoses included cerebral toxoplasmosis
      (4%, n = 7), and tuberculous meningitis (4%, n = 7). Thirty-two (18%) had other
      diagnoses (malaria, bacteraemia, etc.). No aetiology could be elucidated in 28
      persons (15%). Overall mortality was 13.3% (24 of 180) after four months of
      follow up. Those without an established headache aetiology had good clinical
      outcomes, with only one death (4% mortality), and 86% were ambulatory at four
      months. CONCLUSION: In an African HIV-infected ambulatory population presenting
      with new onset headache, aetiology was found in at least 70%. Cryptococcal
      meningitis and sinusitis accounted for more than half of the cases.

PMID- 19765313
TI  - Perinatal acquisition of drug-resistant HIV-1 infection: mechanisms and long-term
      outcome.
AB  - BACKGROUND: Primary-HIV-1-infection in newborns that occurs under antiretroviral
      prophylaxis that is a high risk of drug-resistance acquisition. We examine the
      frequency and the mechanisms of resistance acquisition at the time of infection
      in newborns. PATIENTS AND METHODS: We studied HIV-1-infected infants born between
      01 January 1997 and 31 December 2004 and enrolled in the ANRS-EPF cohort. HIV-1
      RNA and HIV-1-DNA samples obtained perinatally from the newborn and mother were
      subjected to population-based and clonal analyses of drug resistance. If
      positive, serial samples were obtained from the child for resistance testing.
      RESULTS: Ninety-two HIV-1-infected infants were born during the study period.
      Samples were obtained from 32 mother-child pairs and from another 28 newborns.
      Drug resistance was detected in 12 newborns (20%): drug resistance to nucleoside
      reverse transcriptase inhibitors was seen in 10 cases, non-nucleoside reverse
      transcriptase inhibitors in two cases, and protease inhibitors in one case. For 9
      children, the detection of the same resistance mutations in mothers' samples (6
      among 10 available) and in newborn lymphocytes (6/8) suggests that the newborn
      was initially infected by a drug-resistant strain. Resistance variants were
      either transmitted from mother-to-child or selected during subsequent temporal
      exposure under suboptimal perinatal prophylaxis. Follow-up studies of the infants
      showed that the resistance pattern remained stable over time, regardless of
      antiretroviral therapy, suggesting the early cellular archiving of resistant
      viruses. The absence of resistance in the mother of the other three children
      (3/10) and neonatal lymphocytes (2/8) suggests that the newborns were infected by
      a wild-type strain without long-term persistence of resistance when suboptimal
      prophylaxis was stopped. CONCLUSION: This study confirms the importance of early
      resistance genotyping of HIV-1-infected newborns. In most cases (75%), drug
      resistance was archived in the cellular reservoir and persisted during infancy,
      with or without antiretroviral treatment. This finding stresses the need for
      effective antiretroviral treatment of pregnant women.

PMID- 19765316
TI  - Discovering cancer genes by integrating network and functional properties.
AB  - BACKGROUND: Identification of novel cancer-causing genes is one of the main goals
      in cancer research. The rapid accumulation of genome-wide protein-protein
      interaction (PPI) data in humans has provided a new basis for studying the
      topological features of cancer genes in cellular networks. It is important to
      integrate multiple genomic data sources, including PPI networks, protein domains
      and Gene Ontology (GO) annotations, to facilitate the identification of cancer
      genes. METHODS: Topological features of the PPI network, as well as protein
      domain compositions, enrichment of gene ontology categories, sequence and
      evolutionary conservation features were extracted and compared between cancer
      genes and other genes. The predictive power of various classifiers for
      identification of cancer genes was evaluated by cross validation. Experimental
      validation of a subset of the prediction results was conducted using siRNA
      knockdown and viability assays in human colon cancer cell line DLD-1. RESULTS:
      Cross validation demonstrated advantageous performance of classifiers based on
      support vector machines (SVMs) with the inclusion of the topological features
      from the PPI network, protein domain compositions and GO annotations. We then
      applied the trained SVM classifier to human genes to prioritize putative cancer
      genes. siRNA knock-down of several SVM predicted cancer genes displayed greatly
      reduced cell viability in human colon cancer cell line DLD-1. CONCLUSION:
      Topological features of PPI networks, protein domain compositions and GO
      annotations are good predictors of cancer genes. The SVM classifier integrates
      multiple features and as such is useful for prioritizing candidate cancer genes
      for experimental validations.

PMID- 19765317
TI  - Early detection of breast cancer: benefits and risks of supplemental breast
      ultrasound in asymptomatic women with mammographically dense breast tissue. A
      systematic review.
AB  - BACKGROUND: Mammographic screening alone will miss a certain fraction of
      malignancies, as evidenced by retrospective reviews of mammograms following a
      subsequent screening. Mammographic breast density is a marker for increased
      breast cancer risk and is associated with a higher risk of interval breast
      cancer, i.e. cancer detected between screening tests. The purpose of this review
      is to estimate risks and benefits of supplemental breast ultrasound in women with
      negative mammographic screening with dense breast tissue. METHODS: A systematic
      search and review of studies involving mammography and breast ultrasound for
      screening of breast cancer was conducted. The search was performed for the period
      1/2000-8/2008 within the data source of PubMed, DARE, and Cochrane databases.
      Inclusion and exclusion criteria were determined prospectively, and the Oxford
      evidence classification system for diagnostic studies was used for evidence
      level. The parameters biopsy rate, positive predictive value (PPV) for biopsy,
      cancer yield for breast ultrasound alone, and carcinoma detection rate by breast
      density were extracted or constructed. RESULTS: The systematic search identified
      no randomized controlled trials or systematic reviews, six cohort studies of
      intermediate level of evidence (3b) were found. Only two of the studies included
      adequate follow-up of subjects with negative or benign findings. Supplemental
      breast ultrasound after negative mammographic screening permitted diagnosis of
      primarily invasive carcinomas in 0.32% of women in breast density type categories
      2-4 of the American College of Radiology (ACR); mean tumor size for those
      identified was 9.9 mm, 90% with negative lymph node status. Most detected cancers
      occurred in mammographically dense breast ACR types 3 and 4. Biopsy rates were in
      the range 2.3%-4.7%, with PPV of 8.4-13.7% for those biopsied due to positive
      ultrasound, or about one third of the PPV of biopsies due to mammography.
      LIMITATIONS: The study populations included wide age ranges, and the application
      to women age 50-69 years as proposed for mammographic screening could result in
      less striking benefit. Further validation studies should employ a uniform
      assessment system such as BI-RADS and report not only PPV, but also negative
      predictive value, sensitivity and specificity. CONCLUSION: Supplemental breast
      ultrasound in the population of women with mammographically dense breast tissue
      (ACR 3 and 4) permits detection of small, otherwise occult, breast cancers.
      Potential adverse impacts for women in this intermediate risk group are
      associated with an increased biopsy rate.

PMID- 19765318
TI  - Cycling and walking to work in New Zealand, 1991-2006: regional and individual
      differences, and pointers to effective interventions.
AB  - BACKGROUND: Active commuting increases levels of physical activity and is more
      likely to be adopted and sustained than exercise programmes. Despite the
      potential health, environmental, social and economic benefits, cycling and
      walking are increasingly marginal modes of transport in many countries. This
      paper investigated regional and individual differences in cycling and walking to
      work in New Zealand over the 15-year period (1991-2006). METHODS: New Zealand
      Census data (collected every five years) were accessed to analyse self-reported
      information on the "main means of travel to work" from individuals aged 15 years
      and over who are usually resident and employed in New Zealand. This analysis
      investigated differences in patterns of active commuting to work stratified by
      region, age, gender and personal income. RESULTS: In 2006, over four-fifths of
      New Zealanders used a private vehicle, one in fourteen walked and one in forty
      cycled to work. Increased car use from 1991 to 2006 occurred at the expense of
      active means of travel as trends in public transport use remained unchanged
      during that period. Of the 16 regions defined at meshblock and area unit level,
      Auckland had the lowest prevalence of cycling and walking. In contrast to other
      regions, walking to work increased in Wellington and Nelson, two regions which
      have made substantial investments in local infrastructure to promote active
      transport. Nationally, cycling prevalence declined with age whereas a U-shaped
      trend was observed for walking. The numbers of younger people cycling to work and
      older people walking to work declined substantially from 1991 to 2006. Higher
      proportions of men compared with women cycled to work. The opposite was true for
      walking with an increasing trend observed in women aged under 30 years. Walking
      to work was less prevalent among people with higher income. CONCLUSION: We
      observed a steady decline in cycling and walking to work from 1991 to 2006, with
      two regional exceptions. This together with the important differences in travel
      patterns by age, gender and personal income highlights opportunities to target
      and modify transport policies in order to promote active commuting.

PMID- 19765319
TI  - Correlation and comparison of Risser sign versus bone age determination (TW3)
      between children with and without scoliosis in Korean population.
AB  - BACKGROUND: Most studies comparing the Risser staging for skeletal maturity are
      representing the American or European standards which are not always applicable
      to Asian population who have relatively less height and body mass. There is no
      article available that compares the Risser sign and bone age correlation between
      patients with idiopathic scoliosis and patients without scoliosis. MATERIALS AND
      METHODS: To analyze and compare the skeletal age with the Risser sign between
      scoliosis and non-scoliosis group, a cross-sectional study was done in 418
      scoliosis (untreated, bracing or surgically) and 256 non-scoliosis children of
      Korean origin. Relationship was found in both groups using Pearson correlation
      test. RESULTS: In scoliosis group, Pearson correlation exhibited significant
      correlation (p < 0.01) between Risser sign and chronological age (r2 = 0.791 for
      girls, 0.787 for boys) and Risser sign and TW3 age (r2 = 0.718 for girls, 0.785
      for boys). Non-scoliosis group also showed significant relationship (p < 0.01)
      between Risser sign and chronological age (r2 = 0.893 for girls, 0.879 for boys)
      and Risser sign and TW3 age (r2 = 0.913 for girls, 0.895 for boys). Similarly,
      comparing Cobb angles of each patient according to their Risser staging,
      exhibited that if scoliosis remains untreated Cobb angle will increase with the
      increase in their Risser staging (r2 = 0.363 for girls, 0.443 for boys; p <
      0.01). CONCLUSION: Our results showed that chronological age is equally as
      reliable as skeletal age method to compare with Risser sign, and therefore, we do
      not mean to imply that only the Risser sign compared with skeletal age should be
      considered in the decision making in idiopathic as well as non-scoliosis patients
      of Korean ethnicity. Concomitant indicators such as menarchal period, secondary
      sex characteristics, and recent growth pattern will likely reinforce our data
      comparing Risser sign with skeletal age in decision making.

PMID- 19765320
TI  - Transcriptional control of Flt3 ligand targeted by fluorouracil-induced Egr-1
      promoter in hematopoietic damage.
AB  - BACKGROUND: Ionizing radiation (IR) activate the early growth response-1 (Egr-1)
      promoter by production of radical oxygen intermediates (ROIs). Egr-EF, an
      expression vector pCIneo containing Egr-1 promoter cloned upstream of the cDNA
      for Flt3 ligand, was used to treat hematopoietic damage. 5-fluorouracil, a
      commonly used chemotherapeutic agent, cause tumor cell death by producing DNA
      damage and generating ROIs. We therefore hypothesized that clinically employed
      chemotherapeutic agents that increase ROIs could also be employed to activate Egr
      EF in a chemoinducible gene therapy strategy. The goal of this study was to
      explore the effect of Flt3 Ligand gene transcription regulated by fluorouracil
      induced Egr-1 promoter on hematopoietic recovery. METHODS: Human Flt3 Ligand (FL)
      cDNA and enhanced green fluorescent protein (EGFP) cDNA were linked together with
      IRES and inserted into the expression vector pCI-neo under control of the Egr-1
      promoter (Egr-EF). The vector was transfected into the HFCL human bone marrow
      stromal cell line, and these cells were exposed to 5-FU, a chemotherapeutic drug.
      Expression of FL by HFCL/EF cells after 5-FU treatment was determined with ELISA,
      western blot and RT-PCR assays. In addition, the effect of FL from HFCL/EF cell
      culture supernatants on growth of CD34+ cells from cord blood was also studied.
      HFCL/EF cells were injected into CB-17 combined immunodeficient (SCID) mice with
      B16 melanoma. 5-FU was given three days after injection of the HFCL/EF cells. In
      the recipient mice, white blood cell levels in peripheral blood and expression of
      EGFP and FL in human stromal cells were measured. Tumor volumes in tumor-bearing
      mice were also measured. RESULTS: 5-FU treatment increased EGFP levels and
      secreted FL levels in HFCL/EF cells. Supernatants from HFCL/EF cell cultures
      treated with 5-FU increased CD34+ cell growth significantly. HFCL/EF exhibited an
      increase in the number of white blood cells after chemotherapy. CONCLUSION: The
      data presented here support the use of transcriptional control mediated by
      chemoinducible gene therapy to reduce hematopoietic injury associated with 5-FU.

PMID- 19765321
TI  - A randomized trial of chlorhexidine gluconate on oral bacterial pathogens in
      mechanically ventilated patients.
AB  - INTRODUCTION: Dental plaque biofilms are colonized by respiratory pathogens in
      mechanically-ventilated intensive care unit patients. Thus, improvements in oral
      hygiene in these patients may prevent ventilator-associated pneumonia. The goal
      of this study was to determine the minimum frequency (once or twice a day) for
      0.12% chlorhexidine gluconate application necessary to reduce oral colonization
      by pathogens in 175 intubated patients in a trauma intensive care unit. METHODS:
      A randomized, double-blind, placebo-controlled clinical trial tested oral topical
      0.12% chlorhexidine gluconate or placebo (vehicle alone), applied once or twice a
      day by staff nurses. Quantitation of colonization of the oral cavity by
      respiratory pathogens (teeth/denture/buccal mucosa) was measured. RESULTS:
      Subjects were recruited from 1 March, 2004 until 30 November, 2007. While 175
      subjects were randomized, microbiologic baseline data was available for 146
      subjects, with 115 subjects having full outcome assessment after at least 48
      hours. Chlorhexidine reduced the number of Staphylococcus aureus, but not the
      total number of enterics, Pseudomonas or Acinetobacter in the dental plaque of
      test subjects. A non-significant reduction in pneumonia rate was noted in groups
      treated with chlorhexidine compared with the placebo group (OR = 0.54, 95% CI:
      0.23 to 1.25, P = 0.15). No evidence for resistance to chlorhexidine was noted,
      and no adverse events were observed. No differences were noted in microbiologic
      or clinical outcomes between treatment arms. CONCLUSIONS: While decontamination
      of the oral cavity with chlorhexidine did not reduce the total number of
      potential respiratory pathogens, it did reduce the number of S. aureus in dental
      plaque of trauma intensive care patients.

PMID- 19765322
TI  - Nematode infection in the lizard Bogertia lutzae (Loveridge, 1941) from the
      Atlantic Forest in north-eastern Brazil.
AB  - Endoparasites associated with the small bromelicolous lizard Bogertia lutzae, a
      poorly studied phyllodactylid inhabitant of north-eastern Brazil, were studied.
      Fifty-seven specimens collected from the Atlantic Forest of Alagoas state were
      dissected. Only one species of parasite, the nematode Spauligodon
      oxkutzcabiensis, was found, with a prevalence of 22.8%. The intensity of
      infection was 2.62 +/- 1.19, and neither the prevalence nor mean intensity
      differed between the sexes. There was no correlation between lizard body size and
      intensity of infection. An aggregated pattern of distribution (D = 0.813) of S.
      oxkutzcabiensis was found in this lizard host population. Bogertia lutzae
      represents a new host recorded for S. oxkutzcabiensis, a parasite reported for
      the first time for Brazil.

PMID- 19765323
TI  - Susceptibility to praziquantel of male and female cercariae of praziquantel
      resistant and susceptible isolates of Schistosoma mansoni.
AB  - Praziquantel (PZQ) is now widely used for the treatment of human schistosomiasis.
      However, in recent years, there has been a growing concern about the resistance
      of Schistosoma to PZQ. The mechanisms of PZQ action against Schistosoma and
      resistance of Schistosoma to PZQ are poorly understood. Here, we report
      differential susceptibilities to PZQ between male and female cercariae in the PZQ
      susceptible and PZQ-resistant isolates of Schistosoma mansoni, using tail loss as
      a measurement of PZQ action. The miracidia were collected by hatching eggs
      collected from faeces of infected mice. Single-sex cercaria lines were made by
      infecting a single Biomphalaria glabrata snail with a single miracidium. The sex
      of each single-sex cercaria line was identified by a direct W1-specific
      polymerase chain reaction (PCR) technique. Single-sex cercariae of two isolates
      were exposed to four different concentrations of PZQ, respectively. The tail
      shedding of cercariae was observed under a dissecting microscope for five time
      points up to 100 min after adding PZQ. The results showed that male cercariae
      have higher tail-shedding rates than that of female cercariae when PZQ
      susceptible isolates of S. mansoni are exposed to the same concentration of PZQ.
      But this phenomenon was not observed in the PZQ-resistant isolates. This sexual
      differential resistance phenomenon of S. mansoni suggests that resistance to PZQ
      is induced by decreasing the PZQ susceptibility of male worms. The experiment
      described here may also be useful for developing tests to detect PZQ resistance
      in the field.

PMID- 19765324
TI  - The place of rhinoplasty in the ageing face.
AB  - Age-related changes in the skin and underlying tissues of the nose may lead to
      nasal obstruction or an unsatisfactory cosmetic appearance. As the UK population
      ages, the number of older patients seeking advice from an otolaryngologist about
      these problems is increasing, and many of these patients may benefit from a
      rhinoplasty. Quite apart from the practical considerations of operating on more
      delicate ageing tissues, there are a number of psychological, motivational and
      social issues specific to rhinoplasty in the older patient. This review discusses
      these issues, and aims to define the place of rhinoplasty in the ageing face.

PMID- 19765325
TI  - Post-tonsillectomy pseudoaneurysm: an underestimated entity?
AB  - OBJECTIVE: To identify patients undergoing arteriography to verify vascular
      complications of tonsillectomy, with an emphasis on pseudoaneurysm. PATIENTS AND
      METHODS: We undertook a retrospective analysis of the case records of 8837
      patients who had undergone tonsillectomy between 1988 and 2004 at our
      institution, together with a review of expert reports written for professional
      boards and civil courts as well as personal experiences or communication. We also
      conducted a literature review using the PubMed database. RESULTS: We identified
      seven cases with vascular abnormalities. In addition, we identified three cases
      of pseudoaneurysm formation, involving two children and one adult patient, with
      bleeding 21, 36 and 58 days after tonsillectomy. Successful management included
      embolisation (two patients) and revision surgery (one patient). CONCLUSION: Post
      tonsillectomy pseudoaneurysm formation is extremely rare and unrestricted by age.
      Correct diagnosis depends largely on a high index of clinical suspicion. Delayed
      and repeated episodes of gushing haemorrhage with spontaneous cessation appear to
      be a significant clinical marker. Immediate arteriography, with simultaneous
      embolisation, is highly recommended. The lingual artery is the most commonly
      involved vessel.

PMID- 19765326
TI  - Effect of oral tumour size on quality of life judgements by health care
      professionals working with head and neck cancer patients: a pilot study.
AB  - AIM: To investigate whether information about the size of an oral tumour
      influences the multi-disciplinary team's judgement about the quality of life of
      head and neck cancer patients. METHOD: Using a between-group design, two groups
      of health care professionals rated a hypothetical patient on 20 outcome
      variables. The patient description was identical for both groups, except for the
      tumour size. RESULTS: Comparison of variable ratings revealed only three
      significant differences between the groups' predictions and no consistency within
      conditions, suggesting that the participants held few common assumptions about
      the impact of tumour size on a range of patient experiences. CONCLUSION: The lack
      of agreement amongst the health care professionals suggests that, where humane
      judgements are used in treatment decisions for head and neck cancer patients,
      these may be random and inconsistent. Consequently, patients should have a direct
      input into treatment decisions, via formalized quality of life data.

PMID- 19765327
TI  - Magnetic resonance imaging of branchial cleft abnormalities: illustrated cases
      and literature review.
AB  - OBJECTIVE: We report two cases of branchial cleft abnormalities investigated
      using magnetic resonance imaging. BACKGROUND: There appears to be no clear
      imaging technique that is universally recommended for imaging branchial cleft
      abnormalities. Options include fistulography, computed tomography, magnetic
      resonance imaging and ultrasonography. METHOD: Case reports and literature
      review. CASE REPORTS: Two cases, although not unusual in themselves, are
      described to illustrate the use of magnetic resonance imaging to define the
      anatomy and to assist surgical planning. CONCLUSION: Magnetic resonance imaging
      is able to accurately depict the extent and course of branchial cleft
      abnormalities, and in the current cases could have been relied upon to determine
      the necessary surgical procedure. Branchial cleft abnormalities are sufficiently
      rare for magnetic resonance imaging to be recommended as the first-line imaging
      modality.

PMID- 19765328
TI  - Breathing straws.
AB  - Following nasal, septal or endoscopic surgery, it is common practice to insert
      nasal packs in both nasal cavities to achieve haemostasis, if there has been any
      bleeding at the end of the procedure. However, such packs make it difficult for
      patients to breathe, mainly in the first post-operative night which leads to
      discomfort and poor sleep. To enable patients to breathe better with nasal packs
      in situ, we describe a simple technique using trimmed straws and wrapped Netcell
      packs for post-operative care following septal surgery, rhinoplasty and
      endoscopic sinus surgery. These packs also assist suction of any blood or mucous
      from the post-nasal space.

PMID- 19765329
TI  - The dangers of kite flying: pseudoaneurysm of the facial artery following blunt
      trauma.
AB  - OBJECTIVE: Pseudoaneurysms of the facial artery are an extremely rare development
      after blunt trauma. This paper aims to demonstrate the challenges faced during
      the diagnosis and subsequent management of this unusual cause of neck swelling.
      METHOD: We report the presentation, examination, investigation, management and
      potential complications of a case of facial artery pseudoaneurysm secondary to
      blunt arterial trauma, sustained from the string of a flying kite. We also review
      some of the relevant literature on this subject. CONCLUSIONS: Although a
      traumatic pseudoaneurysm is a rare occurrence in the facial region, the inclusion
      of this lesion in the differential diagnosis of soft tissue lesions caused by
      blunt trauma is important if the serious consequences of haemorrhage or
      thromboembolic disease are to be avoided. Prompt access to radiological imaging,
      and multi-disciplinary team input, are essential for effective diagnosis and
      management.

PMID- 19765330
TI  - Novel use of ultrasound-guided endo-cavitary probe to evaluate an impalpable
      parapharyngeal mass.
AB  - AIM: We present a novel, previously undescribed technique of obtaining a biopsy
      from an inaccessible parapharyngeal space mass. METHOD: A modified endo-cavitary
      ultrasound probe was utilised to obtain an intra-oral, image-guided core biopsy
      of a parapharyngeal tumour. The parapharyngeal mass was not accessible to
      percutaneous ultrasound-guided biopsy due to its anatomical location. CONCLUSION:
      To our knowledge, this is the first such modification of the conventional endo
      cavitary probe technique described in the literature. The technique permits
      accurate, well controlled biopsy of lesions located high in the parapharyngeal
      space, under general anaesthesia.

PMID- 19765331
TI  - No evidence of transmission of H5N1 highly pathogenic avian influenza to humans
      after unprotected contact with infected wild swans.
AB  - Highly pathogenic avian influenza (HPAI) subtype H5N1 remains a public health
      threat as long as it circulates in wild and domestic birds. Information on the
      transmissibility of H5N1 HPAI from wild birds is needed for evidence-based public
      health advice. We investigated if transmission of H5N1 HPAI had taken place in
      people that had unprotected contact with infected wild mute swans during an
      incident at the Abbotsbury Swannery in Dorset, England. Thirteen people who had
      been exposed to infected swans were contacted and actively followed up for
      symptoms. Serology was taken after 30 days. We did not find evidence of
      transmission of H5N1 HPAI to humans during the incident. The incident provided a
      rare opportunity to study the transmissibility of the virus from wild birds to
      humans.

PMID- 19765332
TI  - A new multiplex PCR for differential identification of Shigella flexneri and
      Shigella sonnei and detection of Shigella virulence determinants.
AB  - Most of the multiplex PCR (mPCR) used to identify Shigella do not discriminate
      between Shigella species or serotypes. We designed a mPCR to differentiate
      between S. flexneri and S. sonnei strains based on the detection of markers
      associated with the she pathogenicity island described in Shigella. In addition,
      specific primers were included to detect the Shigella virulence determinants ShET
      1 and ShET-2 enterotoxin genes. The analysis of 304 Shigella strains from Chile
      and 79 Shigella strains from other geographic locations indicated that the mPCR
      described here detected all Shigella species and specifically differentiated S.
      flexneri and S. sonnei. The technique was sensitive, reproducible, specific and
      simple to perform, providing a new tool with the potential to be employed for
      epidemiological and diagnostic purposes.

PMID- 19765333
TI  - Genetic influence on the kinetics and associated pathology of the early stage
      (intestinal-hepatic) migration of Ascaris suum in mice.
AB  - The generative mechanism(s) of aggregation and predisposition to Ascaris
      lumbricoides and A. suum infections in their host population are currently
      unknown and difficult to elucidate in humans and pigs for ethical/logistical
      reasons. A recently developed, optimized murine model based on 2 inbred strains,
      putatively susceptible (C57BL/6j) and resistant (CBA/Ca) to infection, was
      exploited to elucidate further the basis of the contrasting parasite burdens,
      most evident at the pulmonary stage. We explored the kinetics of early infection,
      focusing on the composite lobes of the liver and lung, over the first 8 days in
      an effort to achieve a more detailed understanding of the larval dispersal over
      time and the point at which worm burdens diverge. Larval recoveries showed a
      heterogenous distribution among the lobes of the lungs, being higher in the right
      lung of both strains, and in the susceptible strain larvae accumulating
      preferentially in 2 (caudal and middle) of the 4 lobes. Total larval burdens in
      these 2 lobes were largely responsible for the higher worm burdens in the
      susceptible strain. While total lung larval recoveries significantly differed
      between mouse strains, a difference in liver larval burdens was not observed.
      However, an earlier intense inflammatory response coupled with more rapid tissue
      repair in the hepatic lobes was observed in CBA/Ca mice, in contrast to C57BL/6j
      mice, and it is possible that these processes are responsible for restricting
      onward pulmonary larval migration in the resistant genotype.

PMID- 19765334
TI  - Transhydrogenase and the anaerobic mitochondrial metabolism of adult Hymenolepis
      diminuta.
AB  - The adult cestode, Hymenolepis diminuta, is essentially anaerobic energetically.
      Carbohydrate dissimilation results in acetate, lactate and succinate accumulation
      with succinate being the major end product. Succinate accumulation results from
      the anaerobic, mitochondrial, 'malic' enzyme-dependent utilization of malate
      coupled to ATP generation via the electron transport-linked fumarate reductase. A
      lesser peroxide-forming oxidase is apparent, however, fumarate reduction to
      succinate predominates even in air. The H. diminuta matrix-localized 'malic'
      enzyme is NADP-specific whereas the inner membrane (IM)-associated electron
      transport system prefers NADH. This dilemma is circumvented by the mitochondrial,
      IM-associated NADPH-->NAD+ transhydrogenase in catalyzing hydride ion transfer
      from NADPH to NAD+ on the IM matrix surface. Hydride transfer is reversible and
      phospholipid-dependent. NADP+ reduction occurs as a non energy-linked and energy
      linked reaction with the latter requiring electron transport NADH utilization or
      ATP hydrolysis. With NAD+ reduction, the cestode transhydrogenase also engages in
      concomitant proton translocation from the mitochondrial matrix to the
      intermembrane space and supports net ATP generation. Thus, the cestode NADPH-
      >NAD+ system can serve not only as a metabolic connector, but an additional
      anaerobic phosphorylation site. Although its function(s) is unknown, a separate
      IM-associated NADH--> NAD+ transhydrogenation, catalyzed by the lipoamide and
      NADH dehydrogenases, is noted.

PMID- 19765335
TI  - Evidence for high levels of vertical transmission in Toxoplasma gondii.
AB  - Toxoplasma gondii is a highly ubiquitous and prevalent parasite. Despite the cat
      being the only definitive host, it is found in almost all geographical areas and
      warm blooded animals. Three routes of transmission are recognised: ingestion of
      oocysts shed by the cat, carnivory and congenital transmission. In natural
      populations, it is difficult to establish the relative importance of these
      routes. This paper reviews recent work in our laboratory which suggests that
      congenital transmission may be much more important than previously thought. Using
      PCR detection of the parasite, studies in sheep show that congenital transmission
      may occur in as many as 66% of pregnancies. Furthermore, in families of sheep on
      the same farm, exposed to the same sources of oocysts, significant divergent
      prevalences of Toxoplasma infection and abortion are found between different
      families. The data suggest that breeding from infected ewes increases the risk of
      subsequent abortion and infection in lambs. Congenital transmission rates in a
      natural population of mice were found to be 75%. Interestingly, congenital
      transmission rates in humans were measured at 19.8%. The results presented in
      these studies differ from those of other published studies and suggest that
      vertical transmission may be much more important than previously thought.

PMID- 19765336
TI  - Characterization of spliced leader genes of Trypanosoma ( Megatrypanum) theileri:
      phylogeographical analysis of Brazilian isolates from cattle supports spatial
      clustering of genotypes and parity with ribosomal markers.
AB  - Trypanosoma (Megatrypanum) theileri from cattle and trypanosomes of other
      artiodactyls form a clade of closely related species in analyses using ribosomal
      sequences. Analysis of polymorphic sequences of a larger number of trypanosomes
      from broader geographical origins is required to evaluate the clustering of
      isolates as suggested by previous studies. Here, we determined the sequences of
      the spliced leader (SL) genes of 21 isolates from cattle and 2 from water buffalo
      from distant regions of Brazil. Analysis of SL gene repeats revealed that the 5S
      rRNA gene is inserted within the intergenic region. Phylogeographical patterns
      inferred using SL sequences showed at least 5 major genotypes of T. theileri
      distributed in 2 strongly divergent lineages. Lineage TthI comprises genotypes IA
      and IB from buffalo and cattle, respectively, from the Southeast and Central
      regions, whereas genotype IC is restricted to cattle from the Southern region.
      Lineage TthII includes cattle genotypes IIA, which is restricted to the North and
      Northeast, and IIB, found in the Centre, West, North and Northeast. PCR-RFLP of
      SL genes revealed valuable markers for genotyping T. theileri. The results of
      this study emphasize the genetic complexity and corroborate the geographical
      structuring of T. theileri genotypes found in cattle.

PMID- 19765337
TI  - Moving towards an integrated approach to molecular detection and identification
      of Toxoplasma gondii.
AB  - The development of simple, sensitive and rapid methods for the detection and
      identification of Toxoplasma gondii is important for the diagnosis and
      epidemiological studies of the zoonotic disease toxoplasmosis. In the past 2
      decades, molecular methods based on a variety of genetic markers have been
      developed, each with its advantages and limitations. The application of these
      methods has generated invaluable information to enhance our understanding of the
      epidemiology, population genetics and phylogeny of T. gondii. However, since most
      studies focused solely on the detection but not genetic characterization of T.
      gondii, the information obtained was limited. In this review, we discuss some
      widely used molecular methods and propose an integrated approach for the
      detection and identification of T. gondii, in order to generate maximum
      information for epidemiological, population and phylogenetic studies of this key
      pathogen.

PMID- 19765338
TI  - Biological invasion and parasitism: invaders do not suffer from physiological
      alterations of the acanthocephalan Pomphorhynchus laevis.
AB  - Biological invasions expose parasites to new invasive hosts in addition to their
      local hosts. However, local parasites are often less successful in infecting and
      exploiting their new hosts. This may have major consequences for the competitive
      ability of hosts, and finally on the fate of the parasite-host community. In
      Burgundy (Eastern France), the acanthocephalan parasite, Pomphorhynchus laevis,
      infects 2 amphipod species living in sympatry: the native Gammarus pulex and the
      invasive Gammarus roeseli. While P. laevis affects the behaviour and the immunity
      of G. pulex, G. roeseli seems unaffected by the infection. In this study, we
      examined in detail the ability of the parasite to affect the immune system and
      resource storage of both gammarid species. We found that the infection was
      associated with a general decrease of the prophenoloxidase activity, haemocyte
      density, resistance to an artificial bacterial infection and level of sugar
      reserves in G. pulex, but not in G. roeseli. These results demonstrate a
      differential ability of P. laevis to exploit its local and its invasive gammarid
      hosts. Potential mechanisms of these differential physiological alterations and
      their potential consequences on the coexistence of both gammarid species in
      sympatry are discussed.

PMID- 19765340
TI  - Infection success of different trematode genotypes in two alternative
      intermediate hosts: evidence for intraspecific specialization?
AB  - The evolution of host specificity and the potential trade-off between being a
      generalist and a specialist are central issues in the evolutionary ecology of
      parasites. Different species of parasites or even different populations of the
      same species often show different degrees of host specificity. However, less is
      known about intraspecific variation in host specificity within a population. We
      investigated intraspecific variation by experimentally exposing cercariae from
      different clones of the trematode Curtuteria australis to two species of second
      intermediate hosts, the New Zealand cockle Austrovenus stutchburyi and the wedge
      shell Macomona liliana. We found an overall difference in infection success
      between the two bivalve species, with A. stutchburyi being the more heavily
      infected host. However, the cercariae showed a consistent preference for
      encysting at the tip of the bivalve's foot, regardless of host species.
      Importantly, there were no significant differences among parasite clones in
      either relative infection success in the two hosts or preference for the host
      foot tip. This lack of intraspecific variation may be due to the life-history
      traits of both parasite and hosts in our system, which may limit opportunities
      for variation in performance and exploitation strategies in different hosts to
      evolve within the population.

PMID- 19765341
TI  - Cucumispora dikerogammari n. gen. (Fungi: Microsporidia) infecting the invasive
      amphipod Dikerogammarus villosus: a potential emerging disease in European
      rivers.
AB  - Dikerogammarus villosus is an invasive amphipod that recently colonized the main
      rivers of Central and Western Europe. Two frequent microsporidian parasites were
      previously detected in this species, but their taxonomic status was unclear. Here
      we present ultrastructural and molecular data indicating that these two parasites
      are in fact a single microsporidian species. This parasite shares numerous
      characteristics of Nosema spp. It forms elongate spores (cucumiform), developing
      in direct contact with host cell cytoplasm; all developmental stages are
      diplokaryotic and the life cycle is monomorphic with disporoblastic sporogony.
      Initially this parasite was described as Nosema dikerogammari Ovcharenko and
      Kurandina 1987. However, phylogenetic analysis based on the complete sequence of
      SSU rDNA places the parasite outside the genus Nosema and it is therefore
      ascribed to a new genus Cucumispora. The key features characteristic to this
      genus are: presence of a very well-developed, umbrella-shape anchoring disk
      covering the anterior part of polaroplast; arrangement of isofilar polar filament
      into 6-8 coils convoluted with different angles, voluminous diplokaryon, thin
      spore wall and relatively small posterior vacuole containing posterosome. The
      parasite infects most host tissues but mainly muscles. It showed high rates of
      horizontal trophic transmission and lower rates of vertical transmission.

PMID- 19765342
TI  - Intestinal parasites of endangered orangutans (Pongo pygmaeus) in Central and
      East Kalimantan, Borneo, Indonesia.
AB  - Faecal samples from 163 captive and semi-captive individuals, 61 samples from
      wild individuals and 38 samples from captive groups of Bornean orangutans (Pongo
      pygmaeus) in Kalimantan, Indonesia, were collected during one rainy season
      (November 2005-May 2006) and screened for intestinal parasites using sodium
      acetate-acetic acid-formalin-concentration (SAFC), sedimentation, flotation,
      McMaster- and Baermann techniques. We aimed to identify factors influencing
      infection risk for specific intestinal parasites in wild orangutans and
      individuals living in captivity. Various genera of Protozoa (including Entamoeba,
      Endolimax, Iodamoeba, Balantidium, Giardia and Blastocystis), nematodes (such as
      Strongyloides, Trichuris, Ascaris, Enterobius, Trichostrongylus and hookworms)
      and one trematode (a dicrocoeliid) were identified. For the first time, the
      cestode Hymenolepis was detected in orangutans. Highest prevalences were found
      for Strongyloides (individuals 37%; groups 58%), hookworms (41%; 58%),
      Balantidium (40%; 61%), Entamoeba coli (29%; 53%) and a trichostrongylid (13%;
      32%). In re-introduction centres, infants were at higher risk of infection with
      Strongyloides than adults. Infection risk for hookworms was significantly higher
      in wild males compared with females. In groups, the centres themselves had a
      significant influence on the infection risk for Balantidium. Ranging patterns of
      wild orangutans, overcrowding in captivity and a shift of age composition in
      favour of immatures seemed to be the most likely factors leading to these
      results.

PMID- 19765343
TI  - Whole genome amplification (WGA) for archiving and genotyping of clinical
      isolates of Cryptosporidium species.
AB  - Clinical and environmental isolates of pathogens are often unique and may be
      unculturable, yielding a very limited amount of DNA for genetic studies.
      Cryptosporidium in particular are difficult to propagate. Whole genome
      amplification (WGA) is a valuable technique for amplifying genomic material. In
      this study, we tested 5 WGA commercial kits using Cryptosporidium clinical
      isolates. DNA of 5 C. hominis and 5 C. parvum clinical isolates and C. parvum
      IOWA reference strain were used. The majority of the samples were amplified by
      all of the kits tested. The integrity and fidelity of the amplified genomic DNA
      were assessed by sequence analysis of several PCR products of varying length. We
      found evidence that one kit in particular may be more error prone while another
      seemed the more suitable kit for Cryptosporidium clinical samples, generating
      high molecular weight DNA from all the samples with high fidelity. Thus WGA was
      found to be a useful technique for producing amplified DNA suitable for
      downstream genotyping techniques and archiving of Cryptosporidium clinical
      isolates.

PMID- 19765339
TI  - Occurrence and molecular characterization of Cryptosporidium spp. genotypes in
      European hedgehogs (Erinaceus europaeus L.) in Germany.
AB  - Juvenile hedgehogs having insufficient body weight are often brought for
      overwintering to hedgehog rehabilitation centres. Faecal samples of juvenile
      hedgehogs and overwintering hedgehogs (n=188) collected prior to releasing them
      back into the wilderness were examined for the presence of Cryptosporidium
      coproantigen and oocysts. Altogether 56 (29.8%) submitted samples were positive
      for coproantigen. Forty-five (39.5%, n=114) of the positive samples originated
      from newly rescued hedgehogs, while 11 (14.8%, n=74) positive samples were from
      animals that spent several months at the station. Fifteen samples subjected to
      PCR-RFLP analysis on the partial 18S rRNA locus suggested the presence of C.
      parvum. Multilocus sequence typing on partial 60 kDa glycoprotein gene, 18S rRNA,
      actin gene, 70 kDa heat shock protein gene sequences revealed 3 different subtype
      families: IIa, IIc and a new, proposed as VIIa subtype family. Cryptosporidium
      sp. genotype belonging to VIIa subtype family is closely related to C. parvum but
      is genetically distinct being probably a hedgehog-specific Cryptosporidium sp.
      genotype with unknown zoonotical potential. Hedgehogs excreting Cryptosporidium
      oocysts represent a potential source for human infections, but also an
      anthroponotic nature of the IIc subtype family should be reviewed.

PMID- 19765344
TI  - Transmission cycles in parasites. Preface.

PMID- 19765345
TI  - RNA interference in schistosomes: machinery and methodology.
AB  - RNA interference (RNAi) is a potent gene silencing process that is playing an
      increasingly important role in investigations of gene function in schistosomes.
      Here we review what is known about the process in these parasites and provide an
      update on the methodology and machinery of RNAi. Data are presented to
      demonstrate that: (1) not all schistosome genes can be suppressed to the same
      extent, using the methods employed here; (2) while there is variation in the
      level of suppression achieved for one target gene (SmAP) in adult parasites, all
      individuals exhibit robust (>80%) suppression; (3) short interfering RNAs
      (siRNAs) can effect suppression when delivered by soaking (and not just via
      electroporation, as reported previously); (4) Male/female adult pairs need not be
      separated prior to siRNA delivery by electroporation for effective gene
      suppression in both genders and (5) electroporation of siRNAs in medium is as
      efficient as in commercial electroporation buffer. Regarding the machinery of
      RNAi in schistosomes, a homologue of the C. elegans multi-membrane spanning, RNA
      importing protein SID-1 is identified in silico. The gene encoding this protein
      contains 21 exons and spans over 50 kb to potentially encode a 115,556 Mr protein
      (SmSID-1). These analyses, and a review of the literature, permit us to derive
      and present here a draft of potential RNAi pathways in schistosomes.

PMID- 19765346
TI  - Echinococcus metacestodes as laboratory models for the screening of drugs against
      cestodes and trematodes.
AB  - Among the cestodes, Echinococcus granulosus, Echinococcus multilocularis and
      Taenia solium represent the most dangerous parasites. Their larval stages cause
      the diseases cystic echinococcosis (CE), alveolar echinococcosis (AE) and
      cysticercosis, respectively, which exhibit considerable medical and veterinary
      health concerns with a profound economic impact. Others caused by other cestodes,
      such as species of the genera Mesocestoides and Hymenolepis, are relatively rare
      in humans. In this review, we will focus on E. granulosus and E. multilocularis
      metacestode laboratory models and will review the use of these models in the
      search for novel drugs that could be employed for chemotherapeutic treatment of
      echinococcosis. Clearly, improved therapeutic drugs are needed for the treatment
      of AE and CE, and this can only be achieved through the development of medium-to
      high throughput screening approaches. The most recent achievements in the in
      vitro culture and genetic manipulation of E. multilocularis cells and
      metacestodes, and the accessability of the E. multilocularis genome and EST
      sequence information, have rendered the E. multilocularis model uniquely suited
      for studies on drug-efficacy and drug target identification. This could lead to
      the development of novel compounds for the use in chemotherapy against
      echinococcosis, and possibly against diseases caused by other cestodes, and
      potentially also trematodes.

PMID- 19765347
TI  - Schistosomiasis control in Africa: 8 years after World Health Assembly Resolution
      54.19.

PMID- 19765348
TI  - Culture for genetic manipulation of developmental stages of Schistosoma mansoni.
AB  - Genomes of the major human helminth parasites, and indeed many others of
      agricultural significance, are now the research focus of intensive genome
      sequencing and annotation. A draft genome sequence of the filarial parasite
      Brugia malayi was reported in 2007 and draft genomes of two of the human
      schistosomes, Schistosoma japonicum and S. mansoni reported in 2009. These genome
      data provide the basis for a comprehensive understanding of the molecular
      mechanisms involved in schistosome nutrition and metabolism, host-dependent
      development and maturation, immune evasion and invertebrate evolution. In
      addition, new potential vaccine candidates and drug targets will likely be
      predicted. However, testing these predictions is often not straightforward with
      schistosomes because of the difficulty and expense in maintenance of the
      developmental cycle. To facilitate this goal, several developmental stages can be
      maintained in vitro for shorter or longer intervals of time, and these are
      amenable to manipulation. Our research interests focus on experimental studies of
      schistosome gene functions, and more recently have focused on development of
      transgenesis and RNA interference with the longer term aim of heritable gene
      manipulation. Here we review methods to isolate and culture developmental stages
      of Schistosoma mansoni, including eggs, sporocysts, schistosomules and adults, in
      particular as these procedures relate to approaches for gene manipulation. We
      also discuss recent advances in genetic manipulation of schistosomes including
      the deployment of square wave electroporation to introduce reporter genes into
      cultured schistosomes.

PMID- 19765349
TI  - Biological, ultrastructural effect and subcellular localization of aromatic
      diamidines in Trypanosoma cruzi.
AB  - No vaccines or safe chemotherapy are available for Chagas disease. Pentamidine
      and related di-cations are DNA minor groove-binders with broad-spectrum anti
      protozoal activity. Therefore our aim was to evaluate the in vitro efficacy of di
      cationic compounds - DB1645, DB1582, DB1651, DB1646, DB1670 and DB1627 - against
      bloodstream trypomastigotes (BT) and intracellular forms of Trypanosoma cruzi.
      Cellular targets of these compounds in treated parasites were also analysed by
      fluorescence and transmission electron microscopy (TEM). DB1645, DB1582 and
      DB1651 were the most active against BT showing IC50 values ranging between 0.15
      and 6.9 microm. All compounds displayed low toxicity towards mammalian cells and
      DB1645, DB1582 and DB1651 were also the most effective against intracellular
      parasites, with IC50 values ranging between 7.3 and 13.3 microm. All compounds
      localized in parasite nuclei and kDNA (with greater intensity in the latter
      structure), and DB1582 and DB1651 also concentrated in non-DNA-containing
      cytoplasmic organelles possibly acidocalcisomes. TEM revealed alterations in
      mitochondria and kinetoplasts, as well as important disorganization of
      microtubules. Our data provide further information regarding the activity of this
      class of compounds upon T. cruzi which should aid future design and synthesis of
      agents that could be used for Chagas disease therapy.

PMID- 19765350
TI  - Molecular phylogenetic and morphological analysis of haemosporidian parasites
      (Haemosporida) in a naturally infected European songbird, the blackcap Sylvia
      atricapilla, with description of Haemoproteus pallidulus sp. nov.
AB  - The blackcap (Sylvia atricapilla) is a common Palearctic migratory warbler, and
      haemosporidian parasites are common in this species. However, genetic and
      phenotypic diversity of haemosporidians in warblers has been insufficiently
      investigated and poorly linked. We addressed this issue by combining molecular
      and microscopy data for detection of pigment-forming haemosporidians of the
      genera Haemoproteus and Plasmodium. Blood samples from 498 blackcaps were
      collected at 7 different sites in Europe and investigated for these parasites by
      polymerase chain reaction (PCR)-based techniques and microscopic examination. In
      all, 56% of the birds were infected by at least 1 out of 25 distinct
      mitochondrial cytochrome b (cyt b) gene lineages of these haemosporidians. It is
      concluded that the blackcap is infected not only with blackcap specific
      haemosporidians, but also with Haemoproteus majoris, which is a host generalist
      and common in birds belonging to the Paridae. Haemoproteus pallidulus sp. nov. is
      described based on morphology of its blood stages and segments of the cyt b and
      dihydrofolate reductase/thymidylate synthase (DHFR-TS) genes. This study provides
      evidence that genetic diversity of haemosporidian parasites might be positively
      correlated with migratory strategies of their avian hosts; it also contributes to
      the value of both microscopy and molecular diagnostics of avian blood parasites.

PMID- 19765351
TI  - A foodborne norovirus outbreak at a manufacturing company.
AB  - Over 400 office workers from the same unit of a manufacturing company in
      Stockholm County, Sweden, fell ill with gastroenteritis. A retrospective cohort
      study of office workers in the affected unit demonstrated that canteen visitors
      on one day had an increased risk of illness [risk ratio (RR) 27.1, 95% confidence
      interval (CI) 15.7-46.8] compared to non-visitors. A second study, investigating
      canteen visitors' consumption of particular food items, showed that both tomatoes
      from the salad buffet (RR 5.6, 95% CI 3.2-9.6) and hamburgers (RR 4.9, 95% CI 2.4
      9.8) were the most likely vehicles of infection. Norovirus GI.3 (Desert Shield)
      was identified in stool samples from three office workers and from a food handler
      who prepared the tomatoes for the salad buffet and hamburger ingredients before
      vomiting at the workplace on 12 November. The outbreak could have been prevented
      if the food items prepared by the food handler some hours before vomiting had not
      been served.

PMID- 19765352
TI  - Seventy-five years of estimating the force of infection from current status data.
AB  - The force of infection, describing the rate at which a susceptible person
      acquires an infection, is a key parameter in models estimating the infectious
      disease burden, and the effectiveness and cost-effectiveness of infectious
      disease prevention. Since Muench formulated the first catalytic model to estimate
      the force of infection from current status data in 1934, exactly 75 years ago,
      several authors addressed the estimation of this parameter by more advanced
      statistical methods, while applying these to seroprevalence and reported
      incidence/case notification data. In this paper we present an historical
      overview, discussing the relevance of Muench's work, and we explain the wide
      array of newer methods with illustrations on pre-vaccination serological survey
      data of two airborne infections: rubella and parvovirus B19. We also provide
      guidance on deciding which method(s) to apply to estimate the force of infection,
      given a particular set of data.

PMID- 19765353
TI  - Recovery After Psychosis (RAP): a compassion focused programme for individuals
      residing in high security settings.
AB  - BACKGROUND: The aim of the study was to evaluate the effectiveness of a recovery
      group intervention based on compassionate mind training, for individuals with
      psychosis. In particular, the objective was to improve depression, to develop
      compassion towards self, and to promote help seeking. METHOD: A within-subjects
      design was used. Participants were assessed at the start of group, mid-group (5
      weeks), the end of the programme and at 6 week follow-up. Three group programmes
      were run over the course of a year. Nineteen participants commenced the
      intervention and 18 completed the programme. RESULTS: Significant improvements
      were found on the Social Comparison Scale; the Beck Depression Inventory; Other
      As Shamer Scale; the Rosenberg Self-Esteem Inventory and the General
      Psychopathology Scale from the Positive and Negative Syndrome Scale. CONCLUSIONS:
      The results provide initial indications of the effectiveness of a group
      intervention based on the principles of compassionate focused therapy for this
      population. The findings of this study, alongside implications of further
      research are discussed.

PMID- 19765354
TI  - Beyond laterality: a critical assessment of research on the neural basis of
      metaphor.
AB  - Metaphors are a fundamental aspect of human cognition. The major
      neuropsychological hypothesis that metaphoric processing relies primarily on the
      right hemisphere is not confirmed consistently. We propose ways to advance our
      understanding of the neuropsychology of metaphor that go beyond simple
      laterality. Neuropsychological studies need to more carefully control confounding
      lexical and sentential factors, and consider the role of different parts of
      speech as they are extended metaphorically. They need to incorporate recent
      theoretical frameworks such as the career of metaphor theory, and address factors
      such as novelty. We also advocate the use of new methods such as voxel-based
      lesion-symptom mapping, which permits precise and formal tests of hypotheses
      correlating behavior with lesions sites. Finally, we outline a plausible model
      for the neural basis of metaphor. (JINS, 2009, 16, 1-5.).

PMID- 19765355
TI  - Intentional cognitive control impairments in schizophrenia: generalized or
      specific?
AB  - Impairments in intentional-but not unintentional-inhibition have been found in
      schizophrenia, and are thought to contribute to the presence of psychotic
      symptoms. However, it was previously unknown whether this intentional cognitive
      control impairment extends to intentional resistance to interference-another form
      of cognitive control. The current study resolved this issue through administering
      two cognitive control measures: one with a high intentional resistance to
      interference demand and the other with a high unintentional inhibition demand, to
      schizophrenia (n = 61) and healthy control (n = 34) participants. Consistent with
      previous findings, schizophrenia participants' performance on the measures with a
      high unintentional inhibition demand was intact; however, they were impaired on
      the task with high intentional resistance to interference demands compared with
      controls. This latter finding suggests that intentional cognitive control
      impairments previously found in schizophrenia are not specific to inhibition, but
      instead are more general, including both processes requiring inhibition (as
      consistently reported in the literature) and resistance to interference (as found
      in the current study).

PMID- 19765356
TI  - Conflict adaptation and cognitive control adjustments following traumatic brain
      injury.
AB  - Survivors of severe traumatic brain injury (TBI) often demonstrate impairments in
      the cognitive control functions of detecting response conflict and signaling for
      recruitment of cognitive resources to appropriately adjust performance. These
      cognitive control functions can be measured using conflict adaptation effects,
      wherein manifestations of conflict detection and processing are reduced following
      high- relative to low-conflict trials. Event-related potentials (ERPs) were
      collected while 18 survivors of severe traumatic brain injury (TBI) and 21
      demographically matched control participants performed a modified Stroop task.
      The incongruent-minus-congruent trial Stroop effect for trials preceded by
      incongruent (high conflict) and congruent (low conflict) trials were compared for
      behavioral (response time [RT] and error rate) and ERP reflections of cognitive
      control. Behavioral data showed a reduction in the Stroop effect for both control
      and TBI participant RTs when preceded by incongruent trials. The magnitude of
      these effects did not differentiate control and TBI participants. ERP data
      revealed a centro-parietal conflict slow potential (conflict SP) that
      differentiated incongruent from congruent trials. Planned comparisons showed a
      decreased amplitude conflict SP when ERPs were preceded by incongruent trials in
      control, but not TBI participants. Results indicate subtle TBI-related
      impairments in conflict resolution mechanisms in the context of intact RT-related
      conflict adaptation.

PMID- 19765357
TI  - Neuropsychological functioning as a predictor of employment activity in a
      longitudinal study of HIV-infected adults contemplating workforce reentry.
AB  - Cognitive deficits are associated with HIV disease, and HIV-related cognitive
      deficits have been associated with declines in everyday functioning and
      vocational status. We administered a baseline neuropsychological (NP) test
      battery designed to assess estimated full-scale IQ, achievement,
      attention/concentration, executive function, language, mental speed, motor
      function, nonverbal memory, verbal memory, and visual-spatial function to a
      sample of 174 disabled, HIV-positive individuals enrolled in a randomized,
      controlled trial of a vocational-rehabilitation program. We then used these NP
      scores to predict employment at the end of participants' study participation,
      using both hierarchical multiple regression and ordinal logistic regression
      models. The hierarchical multiple regression analyses did not predict
      participants' employment activities at the end of study participation. In the
      ordinal logistic regression model, executive functioning weakly predicted
      employment status at the end of study participation and inspection of the
      predicted classifications revealed that 63% of the participants were incorrectly
      classified using this model. These results suggest that although predicting
      workforce reentry from NP testing may be statistically significant, NP testing
      may be of limited clinical value for informing the workforce reentry of disabled
      people with HIV who are interested in returning to work.

PMID- 19765358
TI  - Identification and management of  familial hypercholesterolaemia:  what does it
      mean to primary care?
AB  - Familial hypercholesterolaemia is one of the most common dominantly inherited
      disorders to be identified in primary care, leading to raised serum cholesterol
      evident from the first year of life. Around 1 in 500 people are affected by this
      condition, but less than 15% of these are currently attending lipid clinics,
      suggesting that the vast majority are unrecognised in general practice. The
      recently released National Institute for Health and Clinical Excellence evidence
      based guideline on the identification and management of familial
      hypercholesterolaemia provides an opportunity to bridge this gap. Primary care
      has a role in systematic and opportunistic case finding, such as recognising the
      relevance of a family history of premature coronary heart disease and/or grossly
      elevated cholesterol. Although affected individuals need specialist care, GPs can
      reinforce the information provided by specialists and support cascade screening
      to other affected members of the extended family.

PMID- 19765359
TI  - Food for thought.

PMID- 19765360
TI  - Intravenous esomeprazole for prevention of recurrent peptic ulcer bleeding.

PMID- 19765361
TI  - NSAIDs and the gastrointestinal tract.
AB  - NSAIDs incur significant gastrointestinal (GI) side effects. The complication
      risk increases with history of peptic ulcer or older age. Helicobacter pylori
      infection and cardioprotective aspirin have independent and additive risks in the
      presence of NSAID use. NSAID enteropathy is increasingly recognized.
      Cardiovascular and GI risk stratification and H. pylori infection testing should
      be done before initiating NSAIDs. An NSAID combined with a proton pump inhibitor
      (PPI) is comparable to cyclooxygenase (COX)-2 inhibitors for gastroprotection,
      but for high-risk patients, COX-2 plus PPI should be considered. Aspirin and COX
      2 inhibitors are associated with reduced colon adenoma risk, but higher dose and
      longer duration of treatment with aspirin appears effective. Hence, patients at
      high risk of colorectal cancer (with significant family or personal history of
      premalignant adenoma) must be identified, and cardiovascular and GI risk must be
      assessed before using these agents as chemopreventive drugs.

PMID- 19765362
TI  - Diabetic diarrhea.
AB  - Diabetic patients with diarrhea may present clinical challenges in diagnosis and
      treatment. Particular diagnoses are more prevalent in diabetic patients than in
      the general population. Medications are often a culprit for chronic diarrhea, and
      the medication list should always be carefully scrutinized for those with
      diarrhea as a side effect. In diabetic patients, metformin is a common cause of
      diarrhea. Diabetic patients are more likely to have associated diseases (eg,
      celiac sprue and microscopic colitis) that present with diarrhea as the sole
      complaint. Ingested sugar-free foods that may contain sorbitol or other agents
      can cause diarrhea in diabetic patients. Finally, diabetic enteropathy can itself
      cause diarrhea. The various etiologies can be diagnosed with a thorough history
      and appropriate diagnostic tests. This article focuses on the etiologies of
      diarrhea that are seen with higher incidence in diabetic patients.

PMID- 19765363
TI  - Clinical significance of inflammatory markers.
AB  - Inflammatory markers play a key role in the evaluation of patients with
      gastrointestinal symptoms. For patients presenting with nonspecific symptoms of
      abdominal pain and diarrhea, distinguishing inflammatory bowel disease from other
      disorders can be difficult, and invasive diagnostic procedures may be required.
      Inflammatory markers can be useful to differentiate patients who may require
      further workup from those who do not. Several serum, fecal, and other markers are
      reviewed for their use in clinical practice. Although no single ideal marker
      exists, a few show promise in diagnosing inflammatory disease, monitoring disease
      activity, and predicting relapse.

PMID- 19765364
TI  - Fructose-sorbitol malabsorption.
AB  - Important dietary carbohydrates such as fructose and sorbitol are incompletely
      absorbed in the normal small intestine. This malabsorption is sometimes
      associated with abdominal complaints and diarrhea development, symptoms
      indistinguishable from those of functional bowel disease. Recently, polymerized
      forms of fructose (fructans) also were implicated in symptom production in
      patients with irritable bowel syndrome (IBS). Evidence from uncontrolled and
      controlled challenge studies suggests that malabsorbed sugars (fructose,
      sorbitol, lactose) and fructans may act as dietary triggers for clinical symptoms
      suggestive of IBS. Further placebo-controlled studies are needed to obtain
      definite conclusions about the role of dietary sugar malabsorption in functional
      bowel disease.

PMID- 19765365
TI  - Bile acids in regulation of intestinal physiology.
AB  - In addition to their roles in facilitating lipid digestion and absorption, bile
      acids are recognized as important regulators of intestinal function. Exposure to
      bile acids can dramatically influence intestinal transport and barrier
      properties; in recent years, they have also become appreciated as important
      factors in regulating cell growth and survival. Indeed, few cells reside within
      the intestinal mucosa that are not altered to some degree by exposure to bile
      acids. The past decade saw great advances in the knowledge of how bile acids
      exert their actions at the cellular and molecular levels. In this review, we
      summarize the current understanding of the role of bile acids in regulation of
      intestinal physiology.

PMID- 19765366
TI  - Serotonin and the GI tract.
AB  - Serotonin (5-hydroxytryptamine, 5-HT) participates in several functions of the
      gastrointestinal tract. Receptors in seven families (5-HT(1)-5-HT(7)) were
      identified, many of which are present on enterocytes, intrinsic and extrinsic
      neurons, interstitial cells, and gut myocytes. Most 5-HT is released from
      enterochromaffin cells in response to physiologic and pathologic stimuli. Roles
      of 5-HT in health include control of normal gut motor activity, secretion, and
      sensation, and regulation of food intake and cell growth. Abnormalities of
      serotonergic function contribute to symptom genesis in functional bowel
      disorders, inflammatory and infectious diseases of the gut, emetic responses to
      varied stimuli, obesity, and dysregulation of cell growth. Therapies acting as
      agonists or antagonists of 5-HT receptors or that modulate 5-HT reuptake play
      prominent roles in managing these conditions, although use of many agents is
      hampered by cardiopulmonary complications. Novel agents are in testing, which may
      exhibit efficacy without significant toxicity.

PMID- 19765367
TI  - Inflammatory bowel diseases and management considerations: fertility and
      pregnancy.
AB  - Young women with inflammatory bowel disease (IBD) pose a unique set of
      challenges. These women and their treating physicians must make difficult choices
      in matters regarding conception, pregnancy, and breastfeeding. This review
      highlights recent evidence and management issues that arise when taking care of
      women with IBD in terms of fertility, outcomes, and medication safety in
      pregnancy and breastfeeding. Ultimately, treatment must be individualized for
      each patient based on the available evidence and the woman's preferences.

PMID- 19765368
TI  - Evolving concepts in Clostridium difficile colitis.
AB  - Clostridium difficile infection (CDI) is the most important cause of nosocomial
      diarrhea. The emergence of a hypervirulent strain and other factors including
      antibiotic overuse contribute to the increasing incidence and severity of this
      potentially lethal infection. CDI has been reported in persons previously
      considered as low risk, such as young healthy persons without exposure to health
      care settings or antibiotics, peripartum women, and children. In patients with
      inflammatory bowel disease, the risk of C. difficile infection is even greater,
      with higher rates of hospitalization, bowel surgery, and mortality. With
      increasing incidence and severity of disease, the need for improved diagnostic,
      treatment, and infection control strategies cannot be overstated.

PMID- 19765369
TI  - Advances in colorectal cancer screening.
AB  - Colorectal cancer (CRC) remains the third most commonly diagnosed cancer and
      second leading cause of cancer death in the United States. Declines in CRC
      incidence and mortality over the past 20 years were attributed to CRC screening.
      Yet, only slightly more than half of the eligible at-risk population acknowledge
      being screened. To effectively meet the demands of screening in an enlarging,
      ethnically diverse, and aging population, a variety of modalities are needed.
      This article provides a focused assessment of effectiveness, limitations, and
      alternative available screening methods. New modalities endorsed in the updated
      guidelines (eg, fecal immunochemical tests, fecal DNA, and CT colonography) are
      reviewed. In addition, advances and updates in existing tests (eg, guaiac-based
      fecal occult blood tests and colonoscopy) are evaluated.

PMID- 19765370
TI  - Common anorectal disorders: diagnosis and treatment.
AB  - Anorectal disorders affect men and women of all ages. Their management is not
      limited to the evaluation and treatment of hemorrhoids. Rather, a spectrum of
      anorectal disorders ranges from benign and irritating (pruritus ani) to
      potentially life-threatening (anorectal cancer). Symptoms are nonspecific, which
      can make the evaluation of patients difficult. In addition, treatment can be
      frustrating because clinicians are hamstrung by a lack of well-designed,
      prospective, clinical trials. Some of the most common anorectal disorders include
      fecal incontinence, pelvic floor dyssynergia, anal fissures, pruritus ani,
      proctalgia fugax, and solitary rectal ulcer syndrome. This article provides an
      update on the evaluation and treatment of common anorectal disorders.

PMID- 19765371
TI  - Serrated adenomas.
AB  - Serrated adenomas are categorized as sessile serrated adenomas (SSAs) and
      traditional serrated adenomas (TSAs). SSAs are more prevalent in the proximal
      colon and lack classic dysplasia, whereas TSAs are more prevalent in the
      rectosigmoid and have cytologic dysplasia. Serrated adenomas may progress to
      colorectal adenocarcinoma through diverse molecular alterations. Colonoscopy is
      the only test for the early detection of serrated adenomas that allows inspection
      of the entire colon and same-session biopsy sampling or polypectomy, if
      necessary. If an endoscopic biopsy at the right colon reveals SSA without
      cytologic dysplasia or biopsy at the rectosigmoid reveals SSA or TSA, those
      polyps should be excised or surgically resected as necessary. Postpolypectomy
      surveillance for removed SSAs without dysplasia and TSAs must be performed at 5-
      and 3-year intervals, respectively, with colonoscopy to prevent recurrence and
      progression to colorectal adenocarcinoma.

PMID- 19765372
TI  - [iPS: should we always get the ultimate proof ?].

PMID- 19765373
TI  - [Efficient combination of clavulanate and beta-lactam antibiotics against
      extensively drug-resistant M. tuberculosis].

PMID- 19765374
TI  - [A promising new class of antituberculous molecules].

PMID- 19765375
TI  - [The hematopoietic cytokine M-CSF as a cure for Alzheimer's disease].

PMID- 19765376
TI  - [Preventing invasive aspergillosis in hematopoietic stem cells transplant
      recipients].

PMID- 19765377
TI  - [Cdc14B/Skp2/p27 : a novel cancer axis of evil?].

PMID- 19765378
TI  - [The OTT-MAL fusion oncogene: another Notch in megakaryoblastic leukemia].

PMID- 19765379
TI  - [BMP6: a key player in iron metabolism].

PMID- 19765381
TI  - [Schizophrenia and toxoplasmosis].
AB  - Schizophrenia is one of the most severe and disabling psychiatric disease that
      affects about 1 % of the adult worldwide population. Aetiology of schizophrenia
      is still unknown but genetic and environmental factors are suspected to play a
      major role in its onset. Recent epidemiologic studies indicate that infectious
      agents may contribute to some cases of schizophrenia. In particular, several
      epidemiological, behavioural and neurochemical studies suggested the existence of
      an association between schizophrenia and past history of primo-infection by the
      Toxoplasma gondii. However, they are some limitations for this hypothesis among
      which the lack of correlation between the geographic distribution of both
      diseases and of direct evidence for the presence of the parasite in schizophrenic
      patients. Nevertheless the identification of physiopathological mechanisms
      related to the parasite could provide a better comprehension to the outcome of
      schizophrenia. Studies on the link between toxoplasmosis and schizophrenia may
      provide interesting data for the diagnosis and the development of new treatments
      for this disorder.

PMID- 19765382
TI  - [Extranuclear functions of protein sumoylation in the central nervous system].
AB  - Post-translational protein modifications play essential roles in many aspects of
      cellular functions and therefore in the maintenance of cell integrity. These
      protein modifications are involved at all stages of neuronal communication within
      the central nervous system. Sumoylation is a reversible post-translational
      protein modification that consists in the covalent labelling of a small protein
      called SUMO to lysine residues of selected target proteins. Sumoylation is a well
      characterized regulator of nuclear functions and has recently emerged as a key
      factor for numerous extranuclear processes. Furthermore, sumoylation has recently
      been shown to modulate synaptic transmission and is also implicated in a wide
      range of neurodegenerative diseases.

PMID- 19765383
TI  - [Neutrophil: foe or friend?].
AB  - Neutrophils are well-recognized phagocytes in the first line of host defense, and
      are also a major source of pro-inflammatory cytokines, chemokines and lipid
      mediators, thereby contributing to the onset and early orchestration of the
      inflammatory response. In contrast, recent studies indicate that neutrophils have
      tools to limit the magnitude and length of an inflammatory response, and may take
      part in engaging the resolution process. This article describes endogenous
      signals that may transform the phenotype of a neutrophil: from a pro-inflammatory
      cell to one that promotes resolution. Adenosine, an autacoid which can be found
      at high concentrations in inflammatory sites, inhibits several inflammatory
      functions of the neutrophil via engagement of the A2A receptor and reshapes the
      profile of lipid mediators and cytokines released, causing cells to terminate the
      release of pro-inflammatory signals while progressing toward resolution. These
      endogenous resolution pathways may represent a key target for better treatments
      of inflammatory diseases.

PMID- 19765384
TI  - [Genetic and environmental variations in an intercellular signaling network].
AB  - Interindividual variation, be it of environmental or genetic origin, is crucial
      for biological evolution as well as in the medical context. This variation is not
      always directly visible, yet may be revealed under some environmental or genetic
      condition. In this essay is presented the example of the developmental model
      system underlying vulva formation in the nematode Caenorhabditis elegans, where
      an intercellular signaling network (EGF-Ras-MAP kinase, Notch and Wnt pathways)
      is involved in spatial patterning of the fates of the vulva precursor cells.
      Variation may be studied at two levels: (1) rare deviations in the system's
      output, i.e. the spatial pattern of vulva precursor cell fates ; (2) so-called <<
      cryptic >> variation in the underlying intercellular signaling network, without
      change in the system's output. Like every biological system, this network
      displays genetic and -environmental epistasis.

PMID- 19765385
TI  - [Interaction of glucocorticoids and the Sonic Hedgehog pathway during brain
      development].
AB  - Corticosteroids have been used for the past 20-30 years to prevent lethal
      consequences of pulmonary and cerebral disorders linked to prematurity. However,
      many data suggest a low risk-benefit ratio, and the long-term emergence of
      adverse neurodevelopmental outcomes objectivated by RMN studies. Although
      multiple mechanisms have been proposed to explain GCs effects on brain
      development, none has clearly emerged so far. A breakthrough study has been
      recently published, which identified the sonic hedgehog (Shh) signaling pathway
      as the target of Gcs action. Shh is a crucial regulator of brain development and
      neural stem/progenitor cells, and GCs suppress Shh-induced proliferation of
      cerebellar progenitor cells ; Shh acts through the induction of the enzyme
      11betaHSD2, which inactivates the GCs corticosterone and prednisolone, but not
      dexamethasone. These data should lead to the development of novel molecules
      (either GC or Shh agonists) both -efficient and neuroprotective.

PMID- 19765386
TI  - [Pandemic and prepandemic H5N1 influenza vaccines: a 2009 update].
AB  - Since 2003, hundreds of infections with H5N1 avian influenza virus have been
      reported in humans with a mortality rate of ca. 60 %, which makes us fear a
      pandemic influenza in a population without pre-existing immunity. Currently, the
      inter-human transmission is limited to persons in close contact with poultry. In
      anticipation of this pandemic threat, a global plan was established in which
      immunization represents a major issue. However, the development of a vaccine is
      related to many specific problems as the manipulation of strains or evaluation of
      immunogenicity. In addition, production delays after identification of the
      pandemic virus are incompressible and the pandemic is likely to develop before a
      vaccine is available. Specific approaches have been developed to produce
      prepandemic vaccines that can induce cross-immunity, partially effective on the
      pandemic strain. In 2009, several prepandemic and pandemic vaccines have obtained
      their licensure authorization and strategies are being developed in case of
      pandemic influenza.

PMID- 19765387
TI  - [Epidemiology of stroke].
AB  - Stroke is a disabling and very heterogeneous disease that has beneficiated from
      major therapeutic improvements over the past 25 years both in terms of preventive
      strategies and acute care. The better knowledge of the epidemiology of stroke has
      allowed to recognize the worldwide burden of the disease, and to identify the
      vascular risk factors. This article reviews the main current data about the
      epidemiology of stroke.

PMID- 19765388
TI  - [Stroke: acute treatments and secondary prevention].
AB  - Stroke unit care is effective to reduce mortality and handicap in all types of
      strokes. In ischaemic strokes t-PA within 3 hours is the standard therapy,
      replaced by aspirin 300 mg when not appropriate. In haemorrhagic stroke, blood
      pressure lowering is recommended although there is no evidence-based data showing
      that it improves the clinical outcome, and coagulation factors are recommended in
      patients under oral anticoagulation. Vascular risk factors should be treated to
      prevent stroke, especially high blood pressure, high blood cholesterol, and
      cigarette smoking. To reduce the risk of any new vascular events after a first
      stroke or TIA, the 3 complementary strategies are: an optimal management of risk
      factors for stroke (for all types of strokes and TIA), an antithrombotic therapy
      (in ischaemic stroke and TIA only), and carotid surgery in severe symptomatic
      stenosis.

PMID- 19765389
TI  - [What's new in biomedical applications for Terahertz (THz) technology].
AB  - Terahertz technologies have recently been applied to develop high resolution
      imaging. Since practical portable systems can be designed, the possibilty has
      emerged to easily screen for biohazards and concealed objects, a procedure which
      usually requires remote analysis. Applications of THz are also envisaged in the
      medical field, because this technology offers a degree of accuracy never reached
      before in molecule analysis. Skin abnormalities and dental health care are two
      promising targets of THz applications. Nevertheless, potential hazards and health
      effects of THz exposure should be monitored carefully, particularly since some
      data suggest induction of genomic instability.

PMID- 19765390
TI  - [Mesoporous silica nanoparticles for two-photon fluorescence].
AB  - Mesoporous silica nanoparticles have unique properties: a specific large surface
      or a narrow casting of the sizes of pores. The perspectives of use are the
      creation of new tools for the premature diagnosis. For these potential biological
      applications, the harmlessness of these nanoparticles must be established.

PMID- 19765391
TI  - [Our Body, the universe within].

PMID- 19765392
TI  - [The irresponsible psychiatric patient, the new actor of the criminal procedure:
      the evolution of the notion of penal irresponsibility].

PMID- 19765393
TI  - [Fundamental ethical principles in the European framework programmes for research
      and development].
AB  - The European Commission is one of the most important international funding bodies
      for research conducted in Europe and beyond, including developing countries and
      countries in transition. Through its framework programmes for research and
      development, the European Union finances a vast array of projects concerning
      fields affecting the citizens' health, as well as the researchers' mobility, the
      development of new technologies or the safeguard of the environment. With the
      agreement of the European Parliament and of the Council of Ministers, the two
      decisional authorities of the European Union, the 7th framework programmes was
      started on December 2006. This program has a budget of 54 billion Euros to be
      distributed over a 7-year period. Therefore, the European Union aims to fully
      address the challenge as stated by the European Council of Lisbon (of March 2000)
      which declared the idea of providing 3% of the GDP of all the Member States for
      the purpose of research and development. One of the important conditions stated
      by the Members of the European Parliament to allocate this financing is to
      ensuring that "the funding research activities respect the fundamental ethical
      principles". In this article, we will approach this aspect of the evaluation.

PMID- 19765394
TI  - [Schistosome genomes: a key step in the war on the worm].

PMID- 19765395
TI  - [Pax4 transdifferentiates glucagon-secreting alpha cells to insulin-secreting
      beta endocrine pancreatic cells].

PMID- 19765396
TI  - Influenza A (H1N1) 2009 monovalent vaccine: laboratory confirmation of vaccine
      breakdowns.

PMID- 19765397
TI  - Modified intra-cerebral challenge assay for acellular pertussis vaccines:
      comparisons among whole cell and acellular vaccines.
AB  - The modified intra-cerebral challenge assay for acellular pertussis vaccines is
      used in Japan, Korea, China and possibly other Asian countries as the potency
      assay for routine release of acellular pertussis (aP) and combination vaccines.
      National reference standards, typically of whole cell pertussis (Pw) vaccine, are
      in use in these countries, but there is no agreed international reference
      standard for acellular pertussis vaccines. We report here the results of a
      collaborative study initiated in September 2006 in which fourteen laboratories
      performing the modified intra-cerebral challenge assay took part. These
      laboratories compared their various national references of Pw vaccine, the third
      International Standard for whole cell pertussis vaccine, a previously studied two
      component freeze-dried aP vaccine preparation coded JNIH-3, and four different aP
      vaccines in combination with diphtheria and tetanus toxoids. The results of this
      study show that the modified intra-cerebral challenge assay works reliably
      although there are inter-laboratory variations in potency estimates. Pw and aP
      vaccines show apparent differences in dose-response lines in some assay systems.
      This indicates dissimilarity in performance in at least some of these assay
      systems. Estimates of relative potency for aP vaccines in terms of the Pw vaccine
      national or in-house reference preparations differ significantly from one
      another. Different mouse strains were used in each country and the different
      strains may also differ in their responsiveness to Pw and aP vaccines. Estimates
      for different types of aP vaccine formulations show less inter-laboratory
      variation in terms of JNIH-3 than in terms of the third IS for Pw vaccine and the
      remaining variation is not apparently related to the different mouse strains.
      This study thus suggests that an aP vaccine standard would improve inter
      laboratory agreement. These data do not show significant dissimilarity in dose
      response lines between JNIH-3 and the various vaccine products included,
      irrespective of the differences in aP components. Available data indicate that
      JNIH-3 is sufficiently stable to serve as an International Standard. On the basis
      of these results and with the agreement of the participants, it was proposed that
      JNIH-3 should be established as an International Standard for acellular pertussis
      vaccine for use in the modified intra-cerebral challenge assay and other
      protective bioassays, with an assigned activity of 34 International Units (IU)
      per ampoule. A WHO Working Group on Standardization of Acellular Pertussis
      Vaccines: potency assay met in Beijing, China, 7-9 November 2007. This group
      considered the report of this study, the comments of the participants and
      implications of the use of JNIH-3 as a reference standard and recommended
      establishment of JNIH-3 as an International Standard. The results of this study
      and the report of the Working Group were submitted to the Expert Committee on
      Biological Standardization (ECBS) of WHO which established JNIH-3 as the first
      International Standard for acellular pertussis vaccine in the modified intra
      cerebral challenge assay and other protective bioassays with an assignment of
      34IU per ampoule in October 2008.

PMID- 19765398
TI  - How much will it hurt? HPV vaccine side effects and influence on completion of
      the three-dose regimen.
AB  - We examined the prevalence of reported pain following human papillomavirus (HPV)
      vaccination and whether it differed from that for other adolescent vaccines or
      affected completion of the HPV vaccine regimen. In 2008, we conducted cross
      sectional surveys with parents of adolescent girls aged 11-20 living in areas of
      North Carolina with elevated cervical cancer rates who had received at least one
      dose of HPV vaccine. Pain from HPV vaccination, while commonly reported by
      parents, was less frequent compared to other adolescent vaccines and did not
      appear to affect vaccine regimen completion. These findings may be important to
      increase HPV vaccination coverage.

PMID- 19765399
TI  - Mannosamine-biotin as a novel masking agent for coating IgG for immune response
      silencing and augmentation of antibody-antigen interaction.
AB  - A variety of protein-coating procedures are used to modify proteins' properties.
      The principle coating agent used is PEGylation, in which proteins are coated by
      conjunction to polyethylene glycol (PEG). In the present study, we describe a
      novel approach that makes use of small molecules with multifunctional groups as
      the protein-coating agent. The new coating molecule was produced by reacting two
      endogenous molecules, mannosamine and biotin, to form mannose-biotin adducts
      (MBA). hIgG was coated with MBA at various MBA/protein ratios. The immunogenicity
      of MBA-coated hIgG was tested in chickens. A dose-responsive effect of MBA/hIgG
      ratio on immune response suppression was detected, with an optimal masking effect
      at a 12:1 ratio. The immune response to MBA-coated hIgG was about eightfold lower
      than that to PEG-coated hIgG. MBA also increased antibody-antigen-binding
      affinity, and decreased recognition of the Fc domain of MBA-coated hIgG by Fc
      receptor and secondary antibodies. While the PEG molecule consists of inert
      repeating units of ethylene oxide with no additional functional group to allow
      for potentially desirable modifications, the MBA has several functional groups,
      including vicinal hydroxyls, which can easily be converted to active residues
      such as aldehydes or carboxyls. This may be of importance for developing passive
      immunizations or for achieving tolerance of the immune response to an immunogenic
      molecule or virus. In summary, we developed a new protein-coating molecule with
      the ability to mask foreign antigens and in the case of antibodies, to enhance
      activity.

PMID- 19765400
TI  - c-Jun, krox-20, and integrin beta4 expression following chronic nerve compression
      injury.
AB  - Limited work has been done to investigate the molecular mechanisms behind the
      process of demyelination and remyelination that occurs in response to chronic
      nerve compression (CNC) injury. In the present study, we investigated the
      expression of the transcription factors krox-20 and c-jun, positive and negative
      regulators of myelination, respectively. A decrease in krox-20 expression and an
      increase in c-jun expression in both its phosphorylated and non-phosphorylated
      states were observed. In addition, we investigated the role of integrins,
      specifically the beta4 subunit of the alpha6beta4 dimer, as a possible upstream
      signal transducer in the signaling cascade leading to demyelination. We detected
      a decrease in beta4 integrin expression at 2 and 4 weeks post-injury and a
      concomitant relocalization to the Schmidt-Lanterman Incisures, suggesting a role
      for the beta4 integrin in facilitating Schwann cell-extracellular matrix
      interaction. The observed changes in transcription factor and integrin expression
      are temporally correlated with the process of demyelination, and suggest further
      investigation to define their definitive role in regulating the myelin response
      to CNC injury.

PMID- 19765401
TI  - The role of residues in binding loop A in desflurane and propofol modulation of
      recombinant 5-HT3A receptor.
AB  - 5-Hydroxytryptamine type 3 (5-HT(3)) receptor is modulated by general anesthetics
      and regarded as a possible site of anesthetic adverse action. Although two amino
      acids located in transmembrane (TM) 2 and TM3 of LGICs were reported as critical
      for allosteric modulation by anesthetics and alcohols, other residues could
      regulate anesthetic modulation. Earlier studies identified the role of glutamate
      129 and phenylalanine 130 in the non-TM extracellular region in the agonist
      binding and coupling in the 5-HT(3A) receptor. We investigated whether these non
      TM amino acids are involved in desflurane and propofol modulation of the 5-HT(3A)
      receptor in mutant 5-HT(3A) receptors (mutants) expressed in Xenopus laevis
      oocytes. E129D and F130Y mutants were functionally expressed but E129Y and F130S
      mutants were not gated by serotonin. The wild type and F130Y mutants demonstrated
      positive modulation by desflurane at 6 and 12vol.%. In contrast, E129D mutants
      were inhibited by desflurane in a concentration dependent manner. Propofol (1-100
      microM) demonstrated depression of the currents in all receptors examined. These
      findings suggest the role of non-TM residues in the extracellular domain in the
      anesthetic modulation of the 5-HT(3A) receptor.

PMID- 19765402
TI  - Electro-acupuncture relieves visceral sensitivity and decreases hypothalamic
      corticotropin-releasing hormone levels in a rat model of irritable bowel
      syndrome.
AB  - Previous studies into electro-acupuncture (EA) treatment of irritable bowel
      syndrome (IBS) have principally focused on the peripheral effects of EA in a rat
      model of IBS. It is not known whether EA exerts central effects in this rat
      model. We have examined the effects of EA on hypothalamic corticotropin-releasing
      hormone (CRH) levels in a rat model of IBS provoked by colorectal distension
      (CRD) and forelimb immobilization. EA was administered once daily to IBS model
      rats over a period of 7 d; untreated IBS rats and controls were also studied. The
      behavioral response to distension was rated according to the abdominal withdrawal
      reflex (AWR) score; hypothalamic CRH levels were measured by radioimmunoassay. We
      report that EA treatment significantly decreased visceral sensitivity to CRD in
      this rat model. In treated animals, EA also decreased hypothalamic CRH to control
      levels. Reduced hypothalamic CRH levels may mediate the beneficial effects of EA
      in this rat IBS model.

PMID- 19765403
TI  - Effects of NT-4 gene modified fibroblasts transplanted into AD rats.
AB  - It is well known that fibroblasts can act as a cell vector to express functional
      protein, like neurotrophin-4 (NT-4). The present study evaluated the effect of NT
      4 gene modified fibroblasts grafted into the hippocampus of AD rat model. AD rats
      were reproduced by bilateral transection of the hippocampal fimbria-fornix. The
      transplanted fibroblasts steadily expressed NT-4 proteins at least 2 months after
      transplantation. This correlated with a significant rescue in the number of
      cholinergic neurons in the host hippocampus. Morris water maze tests demonstrated
      significant improvements in learning and memory, especially in rats receiving NT
      4-modified fibroblasts. The present results showed that NT-4 gene modified
      fibroblasts could provide a long-term and steady expression of NT-4, and it
      significantly improved the behavior of AD rats. These findings should have
      important clinical applications in providing a long-term NT-4 Secretion for the
      treatment of AD.

PMID- 19765404
TI  - Involvement of enkephalins in the inhibition of osteosarcoma-induced thermal
      hyperalgesia evoked by the blockade of peripheral P2X3 receptors.
AB  - Although previous studies describe the up-regulation of purinergic P2X(3)
      receptors expressed at peripheral nociceptive fibers in experimental painful
      neoplastic processes, the analgesic efficacy of P2X(3) receptor antagonists has
      not been tested in these settings. We study here the effect of the P2X(3)
      receptor antagonist, A-317491, on thermal hyperalgesia produced by the
      intratibial inoculation of NCTC 2472 fibrosarcoma cells to C3H/HeJ mice. The
      peritumoral administration of A-317491 (10-100 microg) dose-dependently
      attenuated osteosarcoma-induced thermal hyperalgesia without modifying thermal
      latencies measured in the contralateral paws. This antihyperalgesic effect was
      inhibited by the coadministration of naloxone-methiodide (0.1-1 microg) or the
      systemic injection of the selective mu-opioid receptor antagonist cyprodime (1
      mg/kg), demonstrating the involvement of peripheral mu-opioid receptors.
      Furthermore, the antihyperalgesic effect induced by A-317491, was antagonised by
      the coadministration of an anti-enkephalin antibody supporting the participation
      of endogenous enkephalins. Consistent with this result, the antihyperalgesic
      effect induced by A-317491 was dramatically enhanced by the administration of an
      enkephalin-degrading inhibitor, Debio 0827, as demonstrated by isobolographic
      analysis. This synergism opens the theoretical possibility that the combination
      of both types of drugs could be useful to counteract some nociceptive symptoms
      derived from tumor development.

PMID- 19765405
TI  - Activation of muscarinic M-1 cholinoceptors by curcumin to increase glucose
      uptake into skeletal muscle isolated from Wistar rats.
AB  - Curcumin, an active principle contained in rhizome of Curcuma longa, has been
      mentioned to show merit for diabetes through its anti-oxidative and anti
      inflammatory properties. In the present study, we found that curcumin caused a
      concentration-dependent increase of glucose uptake into skeletal muscle isolated
      from Wistar rats. This action was inhibited by pirenzepine at concentration
      enough to block muscarinic M-1 cholinoceptor (M(1)-mAChR). In radioligand binding
      assay, the binding of [(3)H]-pirenzepine was also displaced by curcumin in a
      concentration-dependent manner. In the presence of inhibitors for PLC-PI3K
      pathway, either U73122 (phospholipase C inhibitor) or LY294002 (phosphoinositide
      3-kinase inhibitor), curcumin-stimulated glucose uptake into skeletal muscle was
      markedly reduced. In Western blotting analysis, the membrane protein level of
      glucose transporter 4 (GLUT4) increased by curcumin was also reversed by blockade
      of M(1)-mAChR or PLC-PI3K pathway in a same manner. In conclusion, the obtained
      results suggest that curcumin can activate M(1)-mAChR at concentrations lower
      than to scavenge free radicals for increase of glucose uptake into skeletal
      muscle through PLC-PI3-kinase pathway.

PMID- 19765406
TI  - Stress, coping, and disease.

PMID- 19765407
TI  - Recommendations on diagnosis, treatment, and monitoring for Gaucher disease.

PMID- 19765408
TI  - Guidelines to diagnosis and monitoring of Fabry disease and review of treatment
      experiences.

PMID- 19765409
TI  - Guidelines for the management of mucopolysaccharidosis type I.

PMID- 19765410
TI  - The Brazilian consensus on the management of Pompe disease.

PMID- 19765411
TI  - The 11th Congress of the Middle East Society for Organ Transplantation took place
      in Shiraz under the auspices of the Iranian Executive Committee in an atmosphere
      of scientific devotion and academic excellence. Preface.

PMID- 19765412
TI  - Attitudes of medical students about brain death and organ donation.
AB  - INTRODUCTION: There have been publications on the attitudes of the general
      Iranian population and health care personnel about brain death and organ
      donation; however, there is little information about such attitudes of medical
      students. In 2006, a survey was conducted in Tehran about the attitudes of
      medical students in a hospital with a transplantation program. MATERIAL AND
      METHODS: The general population, health care personnel, and medical students were
      surveyed, and data were extracted from interviews with 41 medical students. The
      survey included 35 items about attitudes toward brain death and organ
      transplantation. RESULTS: Nine students (22.0%) had ever seen a transplant
      recipient, and 7 (17.1%) had ever seen a brain-dead patient. Thirty-four students
      (82.9%) agreed with organ donation after brain death. Six students (14.6%) had
      received information through university lectures, and 40 (97.5%) perceived a need
      for further information about organ donation and brain death in the university
      curriculum. Nine students (22.0%) had an organ donor card. CONCLUSION: Most
      Iranian medical students have neither been exposed to brain death or organ
      recipients nor received appropriate information about organ donation and
      transplantation.

PMID- 19765413
TI  - Issuing donor cards in a single center in Iran: results of the first 3 years.
AB  - INTRODUCTION: Issuing an organ donation card has become a goal for procurement
      units to solve the organ shortage. The number of issued cards is an index of the
      attitudes or even actions of communities toward brain-dead donations. In the
      present study, we have reported the characteristics of issuing organ donation
      cards in a single organ procurement unit in Iran. MATERIALS AND METHODS: This
      retrospective study used an organ donation willingness database for 3 years after
      launching the unit. We used the registration data of the first 3 years of its
      activity from August 1, 2005, to July 31, 2008. For each organ donation
      volunteer, we extracted demographic data, organs to be donated, and source of
      their knowledge about the organ donation card system. RESULTS: During the study
      period, donor cards were issued to 172,290 volunteers; a monthly mean of 4785
      registries. Among the total volunteers, 54.2% were females: with 50.7% between 21
      to 30 years, 35.2% with an educational level less than a high school diploma, and
      35.7% introduced by their friends. The volunteers were more willing to donate
      heart, kidney, liver, lung, and tissue donations, respectively. Out of the total
      number of volunteers, 94.1% were willing to donate all organs. An increasing
      trend was seen in the donation cards issued during the study period. CONCLUSION:
      Following 3 years of activity, a single center has issued nearly 200,000 cards.
      The rate at which organ donor cards are issued is increasing, which puts emphasis
      on establishment of funding for other organ procurement units. This information
      may be useful to program the field of brain-dead donations in this country.

PMID- 19765414
TI  - Knowledge and attitude of donor cardholders toward organ and tissue donation and
      transplantation in an Iranian tissue bank: a case-control study.
AB  - BACKGROUND: Cadaveric organ shortage is the most important obstacle to more
      widespread provision of transplants. Many factors influence the donation rate:
      social factors, religion, familial relations, and especially knowledge and
      attitudes toward organ and tissue donation and transplantation. Increasing public
      awareness can reform the incorrect beliefs and myths about donation and
      transplantation. This study investigated knowledge and attitudes of donor
      cardholders toward organ and tissue donation as well as transplantation. METHODS:
      This case-control study was performed in 2006 among 178 donor cardholders and the
      same number of a control group who completed a questionnaire including 23
      questions and demographic information. FINDINGS: Knowledge and attitude among the
      cardholder was significantly greater than the control group (P < .05). We
      observed a inverse correlation between age and a positive attitude toward
      donation and transplantation among cardholders. CONCLUSION: This study suggested
      that the main reasons for refusal to donate organ and tissue were insufficient
      knowledge and negative attitudes due to misinformation regarding donation and
      transplantation. We believe that educating and motivating the public via the mass
      media can increase the rate of consent for organ and tissue donation and
      transplantation.

PMID- 19765415
TI  - Is the annual number of deceased donor kidney transplantations in Iran lower than
      the Middle Eastern countries?
AB  - Deceased donor organ donation is inadequate; hence, the number of patients on the
      waiting lists is progressively growing in the world. However, in Iran the
      deceased donor rate has increased over the past 10 years, from less than 1% by
      the end of year 2000 to almost 16.3% (approximately 311 cases) of kidney
      transplantations in 2007. Although the percentage of deceased donor kidney
      transplantation in some countries of the region are higher than Iran, the
      absolute annual number in Iran is higher than the Middle Eastern countries. The
      outlook for deceased donor kidney transplantation practice in Iran is promising.
      Meanwhile, the annual number of kidney transplantations from deceased donors in
      Baqiyatallah hospital, as the second transplant unit in terms of the volume of
      kidney transplantation in Iran, increased from 0.4% in 2002 to 14% and 31% in
      2007 and 2008, respectively.

PMID- 19765416
TI  - Age and sex predict PaO2/FiO2 ratio in brain-dead donor lungs.
AB  - OBJECTIVES: To define the prevalence of various ranges of the ratio of partial
      arterial oxygen tension to fraction of inspired oxygen (Pao(2)/Fio(2)) and to
      determine correlative and predictive variables of donor lung Pao(2)/Fio(2).
      MATERIAL AND METHODS: From the brain death database of Masih Daneshvari Hospital
      Organ Procurement Center, we extracted demographic data, cause of injury, patient
      clinical condition, and laboratory findings as independent data. Donor lung
      suitability was determined with an oxygen challenge test, with results of 400 mm
      Hg considered ideal; 300 to 399 mm Hg, good; 200 to 299 mm Hg, borderline; and
      less than 200 mm Hg, not acceptable. RESULTS: Using the Pao(2)/Fio(2) cutoff
      points, 6.7% of donor lungs were considered ideal; 26.7%, good; 40%, borderline;
      and 26.7%, unacceptable. Mean (SD; range) Pao(2)/Fio(2) was 266.6 (85.6; 110
      460). The Pao(2)/Fio(2) was significantly correlated with age (r = -0.35; P =
      .02). After entering the study variables into a linear regression model, age (
      2.3; P = .008) and sex (51.5; P = .04) were significant predictors of donor lung
      suitability (R(2) = 0.95; P < .001). CONCLUSION: Results of oxygen challenge
      tests demonstrated better suitability of lungs from male and younger brain-dead
      donors. This finding is independent of other variables including cause of brain
      death and clinical and paraclinical data.

PMID- 19765417
TI  - Organ retrieval from brain-dead patients by a single organ procurement center in
      Iran.
AB  - INTRODUCTION: The majority of transplantations depend solely on cadaveric organs.
      In recent years, special focus has been directed toward brain-dead patients in
      Iran, but it seems that there is limited information regarding the
      characteristics of cadaveric organ donation in our country. MATERIALS AND
      METHODS: This is a retrospective analysis of data of our Organ Procurement Unit
      (OPU), which is one of the most active organ procurement units in Iran. We
      incorporated the data on all organ donations from brain-dead patients between
      2004 and 2008 into the present study. Demographic characteristics of the patients
      along with data regarding brain death and organ donation were extracted from
      already registered data on patients. RESULTS: Among 93 brain-dead patients
      registered in the database of the OPU, organs were retrieved from 85% (n = 79).
      Out of the 14 patients from whom no organ was retrieved, the cause for this
      failure was death before donation in 85% (n = 12). The numbers of donated organs
      varied between zero and six (mean +/- standard deviation = 3.1 +/- 1.7). The most
      donated organs in terms of frequency and count were: right kidney (n = 68;
      73.1%), left kidney (n = 67; 72%), liver (n = 63; 67.7%), heart (n = 40; 43%),
      pancreas (n = 5; 5.4%), and lung (n = 4; 4.3%). DISCUSSION: The overall organ
      retrieval rate from brain-dead patients by this OPU was comparable to that of
      developed countries; however, we still believe we can improve this rate/scale.

PMID- 19765418
TI  - Lung donation and causes behind its failure: a single-center experience.
AB  - INTRODUCTION: Brain-dead patients are almost the only source of organs for lung
      transplantation, and lungs fall within the area of the least harvested organs. As
      a result, maintaining the highest possible harvest rate is a must for the lung
      transplantation system. In the present study, the harvest rate of lungs and also
      the causes of failure to donate the lungs is reported for brain-dead patients in
      our organ procurement unit. MATERIALS AND METHODS: After going through the brain
      death database at our organ procurement unit between 2004 and 2008, we included
      all 93 brain deaths in this hospital. The lung donation rate was reviewed to
      examined the causes for failure to donate lungs. RESULTS: From the total brain
      dead patients registered in the database, only 4 (4.6%) patients donated their
      lungs. The causes of failure to donate a lung were not suitable lungs among 78
      (83.8%) because they had an unacceptable oxygen challenge test results (<300 mm
      Hg). Another 11 patients had acceptable oxygen challenge test results, but
      donation failed in their case as well due to most frequently to pulmonary
      aspiration. CONCLUSION: In this center, only a small percentage of lungs are
      appropriate for harvest in brain-dead patients, because many patients' lungs do
      not meet the criteria with unacceptable oxygen challenge test results. Patients
      with proper test results may fail to donate lungs due to pulmonary aspiration.
      More aggressive care of the patients may have an important role in keeping them
      in good condition and helping to preserve the organs for harvest. For this
      purpose, further training of intensive care unit staff and physicians are among
      the suggested steps to enhance the quality of care, which in turn can maximize
      the lung harvest rate.

PMID- 19765419
TI  - Transperitoneal laparoscopic living donor nephrectomy: 2 years' experience.
AB  - BACKGROUND: Due to the shortage of organ donations and the rising number of
      patients with terminal renal insufficiency, living donor kidney donation has
      become increasingly important during recent years. Hand-assisted laparoscopic
      living donor nephrectomy (LLDN) is an alternative to the conventional open
      approach and may decrease the surgical trauma to the donor. The aim of this study
      was to report our experience with this technique. MATERIALS AND METHODS: We
      reviewed demographic data, operative duration, hospital stay, and postoperative
      complications among 100 LLDNs performed from August 2006 to July 2008. We also
      performed a retrospective analysis of chemical and biochemical data of
      recipients. RESULTS: Thirty female and 70 male subjects of mean age of 35.88 +/-
      12.21 years were operated on during this period. The mean operative time for
      donor nephrectomy was 138.30 +/- 31.92 minutes (range 60-205) and for recipients,
      87.66 +/- 11.79 minutes (range = 75-120), with a mean warm ischemia time of 5.19
      +/- 1.76 minutes (range = 2-8). The donors' mean hospital stay was 28.34 +/- 8.31
      hours (range = 24-72). Five donor operations were converted to open nephrectomy
      because of uncontrolled bleeding or abnormal anatomy. There was no need for blood
      transfusions or reoperations in the donors. Mean hospital stay for the recipients
      was 9.44 +/- 3.61 days (range = 5-22). Creatinine and blood urea nitrogen
      decreased from preoperative values of 10.46 +/- 3.73 and 66.10 +/- 25.16 to 1.39
      +/- 0.38 and 29.64 +/- 8.83 mg/dL at discharge. The renal graft was rejected in
      two cases due to immunologic causes without any response to therapy. There was no
      vascular thrombosis in the transplanted kidneys. CONCLUSION: LLDN is a viable
      alternative to the standard open nephrectomy. It may have a positive impact on
      the donor pool by minimizing disincentives to living donation. The results of our
      program were acceptable; this approach may be the procedure of choice in the
      future in our center.

PMID- 19765420
TI  - Can Doppler ultrasonographic indices of the renal artery predict the presence of
      supernumerary renal arteries?
AB  - BACKGROUND: Variations of the renal arteries, including the presence of
      supernumerary renal arteries, are important to be identified prior to renal
      transplant. Angiography has been the gold standard test for the pretransplant
      evaluation of the renal vasculature. However, this modality is expensive and
      invasive. The aim of this study was to assess whether Doppler ultrasonographic
      (DU) indices of the renal artery could predict the presence of supernumerary
      renal arteries. METHODS AND MATERIALS: Retrospectively, we analyzed multidetector
      computed tomography angiography (presence or absence of the supernumerary renal
      artery), DU (peak systolic velocity, resistive index, pulsatility index, end
      diastolic velocity, and acceleration time) findings of 30 healthy potential renal
      transplant donors. Recipient operator characteristic (ROC) curves were used to
      examine the predictive values of the available DU indices for supernumerary renal
      arteries. RESULTS: The mean age of donors was 28.4 +/- 4.1 years. Of 60 kidneys
      evaluated, a supernumerary renal artery was found in 10%. The ROC curve analysis
      revealed an area under the curve of noninformative (below 0.5) for all DU
      parameters, indicating that none of the studied parameters could predict the
      presence of a supernumerary renal artery. CONCLUSIONS: Although the smaller
      diameter of the main renal artery has previously been found to predict the
      presence of supernumerary renal arteries, the present study revealed that DU
      indices of the renal artery may not indicate the presence of supernumerary renal
      arteries.

PMID- 19765421
TI  - Origination angle of renal artery has no role in renal artery pattern.
AB  - INTRODUCTION: Renal artery (RA) anatomy plays a critical role in selecting
      donors. During the present study, we sought to evaluate the physiological role of
      RA origination angle for the presence of an accessory RA or its early branching.
      METHODS: During the present cross-sectional study (August 2005-October 2007), 143
      candidates for kidney donation underwent RA angiography by 64 multidetector
      computed tomographic angiography. We assessed the RA diameter, distance to first
      branching, presence of accessory RA, and early branching, as well as the
      origination angle of RA from aorta in coronal plane (alpha angle). RESULTS: The
      male-to-female ratio was 96:47 with an overall mean age of 27.42 +/- 4.55 years.
      The alpha angle, sine, cosine of the alpha angle and the deviation factor were
      not significantly different between kidneys with versus without an accessory
      artery or between the RA with versus without an early branching. Only the RA
      diameter (P = .047) and the distance of RA to the branching (P < .001) in kidneys
      with an accessory RA were significantly lower and higher than those without an
      accessory RA, respectively. Also the distance of the RA to the branching was
      significantly less in kidneys with an early branching (P < .001). The RA diameter
      directly correlated with the RA origination angle (r = .191, P = .001), while
      there was no correlation between the distance to RA branching and the RA
      origination angle (r = -.060, P = .311). CONCLUSION: The origination angle of the
      RA from aorta has no role in the early branching or accessory RA development.
      There was a direct correlation between the RA diameter and the RA origination
      angle.

PMID- 19765422
TI  - Development of a varicocele following left-sided nephrectomy in kidney donors.
AB  - INTRODUCTION: Most kidney transplantation surgeons tend to prefer the left-sided
      kidney for donation. Because one of the veins to join the left renal vein is the
      left testicular (gonadal) vein, its flow may be damaged by manipulation of the
      left renal vein during left-sided nephrectomy. We sought to evaluate changes of
      the left-sided pampiniform venous plexus and testis following left-sided
      nephrectomy in kidney donors. METHODS: During the present cross-sectional study
      (June 2007-July 2008), 54 healthy males who were candidates for left kidney
      donation underwent an ultrasound study of the left-sided pampiniform venous
      plexus diameter as well as the left testis size before and 4 months after left
      sided nephrectomy. RESULTS: The patient mean age was 25.07 +/- 2.49 years. The
      mean diameters of left pampiniform vein before versus 4 months after nephrectomy
      were 1.37 +/- 0.40 versus 2.04 +/- 0.49 mm, respectively. The mean sizes of left
      testis before and 4 months after nephrectomy were 21.86 +/- 2.47 versus 21.50 +/-
      2.17 mL, respectively. The mean left pampiniform vein diameter significantly
      increased at 4 months after left-sided nephrectomy (P < .001), but the mean left
      testis size was not significantly changed (P = .136). CONCLUSION: Four months
      after left-sided nephrectomy, the left pampiniform venous plexus diameter
      increased, whereas there was no significant change in left testis size.
      Therefore, in patients with left-sided nephrectomy, a high risk of varicocele may
      be predicted.

PMID- 19765423
TI  - The effect of ischemic preconditioning of the pancreas on severity of
      ischemia/reperfusion-induced pancreatitis after a long period of ischemia in the
      rat.
AB  - BACKGROUND: The role of ischemia/reperfusion injury in the pathogenesis of acute
      pancreatitis is still ill-defined. It is accepted, however, that
      ischemia/reperfusion induces the development of postimplantation pancreatitis
      that is responsible for considerable morbidity. Preconditioning by brief exposure
      to ischemia protects the organ against damage evoked by subsequent severe
      ischemia. This study was undertaken to examine whether two brief ischemic periods
      protect the pancreas against severe ischemia/reperfusion-induced pancreatitis.
      MATERIALS AND METHODS: This study was performed on 30 rats in three groups. The
      first group (control) underwent a laparatomy without clamping of any artery. The
      second group underwent 30-minute clamping of the inferior splenic artery followed
      by 1-hour reperfusion of the pancreas, and the third group underwent clamping of
      inferior splenic artery (2 x 5 minutes with 5-minute interval) as ischemic
      preconditioning and then 30-minute clamping of inferior splenic artery followed
      by 1-hour reperfusion. RESULTS: Exposure to 30-minute pancreatic ischemia
      followed by 1-hour reperfusion led to the development of severe alterations
      greater than the other group that underwent ischemic preconditioning and then
      ischemia/reperfusion. Ischemia preconditioning applied prior to induction of
      pancreatitis reduced plasma lipase and interleukin-1beta concentrations as well
      as less histological signs of pancreatic damage. CONCLUSION: We concluded that
      pancreatic ischemic preconditioning reduced the severity of ischemia/reperfusion
      induced pancreatitis. This effect seemed to be related at least in part to the
      release of the proinflammatory mediator interleukin-1beta.

PMID- 19765424
TI  - Role of postreperfusion subcapsular wedge biopsies in predicting initially poor
      graft function after liver transplantation.
AB  - Preservation injury is a major contributing factor to primary allograft failure
      or poor initial graft function after an orthotopic liver transplant (OLT). We
      examined the histopathological findings from postreperfusion wedge biopsy
      specimens in relation to early graft function during the first postoperative week
      among OLT patients at our center. We reanalyzed subcapsular postreperfusion
      biopsy specimens from 88 patients to histologically grade the lesions. Grafts
      were grouped as good function, initial poor function (an alanine aminotransferase
      or aspartate aminotransferase level >1500 IU/L during week 1), or primary
      nonfunction (death or retransplantation). Only 1 patient experienced primary
      nonfunction; the remaining patients fell into the other 2 groups: ie, good
      function or initial poor function. When patients were compared using numerous
      morphologic and clinical features, no statistical relation was observed regarding
      clinical data on bile duct complications, donor type, graft volume, patient age,
      or type of stent. Histological features of neutrophilic infiltration of the
      subcapsular region, hepatocellular ballooning, and macro/microvesicular steatosis
      were not related to initial poor graft function; in contrast, there were
      prominent sinusoidal neutrophilic infiltrations and hepatocellular necrosis.
      Preservation-reperfusion injury (grade 2 or grade 3 neutrophilic infiltration)
      occurred in 78.6% of initial poor function patients and in 39.7% of good function
      patients. Subcapsular neutrophilic infiltration, a sign of surgical hepatitis,
      did not provide prognostic information about graft survival. Similar to other
      studies, we observed neutrophilic infiltration and necrosis away from the capsule
      to predict subsequent graft function.

PMID- 19765425
TI  - Hepatic changes during various periods of reperfusion after induction of renal
      ischemia in rats.
AB  - BACKGROUND: Recent studies have suggested that ischemic damage to the kidneys
      causes liver tissue alterations. Thus, the morbidity and mortality in patients
      with acute renal failure (ARF) may be related to liver complications as well as
      to renal injury. The aim of the present study was to assess the hepatic changes
      during various periods of reperfusion after induction of renal ischemia. METHODS:
      Forty male rats were subjected to either a sham operation or to a 45-minute
      ischemia followed by 1, 3, 6, or 24 hours of reperfusion. Arterial pressure was
      continuously monitored. Blood samples were drawn to measure serum creatinine and
      blood urea nitrogen (BUN). RESULTS: We evaluated hepatic concentrations of
      interleukin (IL)-10 and tumor necrosis factor (TNF)-alpha. Ischemia reperfusion
      (IR) caused significant reductions in renal function as demonstrated by increased
      values of serum creatinine and BUN. These rats also showed significant increases
      in hepatic TNF-alpha and IL-10 concentrations. The most significant changes among
      inflammatory factors in the liver were observed at 3 hours of reperfusion: TNF
      alpha, 616 +/- 41 vs 215 +/- 16, and IL-10, 926 +/- 73 vs 125 +/- 34, pg/100 mg
      tissue (P <or= .05). Twenty-four-hour reperfusion reduced the extent of liver
      injury. DISCUSSION: Renal IR affects liver inflammatory status, possibly due to
      increased renal production or impaired clearance of mediators of tissue injury,
      namely proinflammatory cytokines. The reduction in liver injury at 24 hours of
      reperfusion compared with the other groups, suggested activation of late
      protective mechanisms. These observations may be important for clinical
      interventions to reduce the morbidity and mortality of ARF.

PMID- 19765426
TI  - Pulmonary hypertension in patients with end-stage renal disease undergoing renal
      transplantation.
AB  - INTRODUCTION: Pulmonary hypertension (PHT) has been reported to occur in a
      considerable proportion of patients with end-stage renal disease (ESRD). It is a
      progressive condition of the pulmonary circulation that poses prognostic
      importance. In this study, we sought to investigate the prevalence and the
      predictors of PHT among ESRD patients undergoing renal transplantation. PATIENTS
      AND METHODS: We retrospectively evaluated the records, clinical and demographic
      data as well as laboratory results of 500 adult patients who underwent renal
      transplantation at our institution. A comprehensive Doppler echocardiographic
      examination was performed in all patients as part of the preoperative assessment.
      Systolic pulmonary artery pressure (SPAP) was calculated using Bernoulli
      equation; a value of >30 mm Hg was accepted as PHT. RESULTS: The mean age of the
      study population was 31.6 +/- 10.2 years. The mean duration of dialysis was 40
      months; 432 patients (86.4%) were on hemodialysis (HD) and 68 (13.6%) on
      peritoneal dialysis (PD). PHT was detected in 85 (17%) patients with a mean SPAP
      of 46.7 +/- 8.7 mm Hg (range = 35-75 mm Hg). The mean age, sex, and laboratory
      variables were similar between patients with versus without PHT (P > .05 for
      all). The mean duration of dialysis therapy was longer in the PHT group than
      those subjects with normal SPAP (50.8 vs 38.5 months; P = .008). Concerning the
      type of dialysis, the ratio of patients having PHT was higher in the HD compared
      with the PD group (18.8% vs 5.9%; P = .008). The prevalence of chronic
      obstructive pulmonary artery disease, asthma, smoking, hypertension, and diabetes
      mellitus did not differ between patients with versus without PHT (P > .05 for
      all). CONCLUSION: The findings of this study revealed that PHT was a common
      clinical condition among patients with ESRD evaluated for renal transplantation.
      The time on renal replacement therapy particularly HD as the treatment was
      associated with greater prevalences. Since it may be of prognostic importance in
      patients undergoing renal transplantation, a careful preoperative assessment
      including a comprehensive Doppler echocardiographic examination is needed to
      identify PHT.

PMID- 19765427
TI  - Safety of low-dose cyclosporine therapy before transplantation in kidney
      allograft recipients.
AB  - INTRODUCTION: Graft dysfunction immediately posttransplantation can vary from
      subtle slowing of the expected decrease in creatinine concentration to frank
      oliguria requiring dialysis therapy for days to weeks. Risk factors for slow and
      delayed graft function include prolonged preservation, older donor age, and high
      plasma renin activity in the recipient. Cyclosporine (CsA) nephrotoxicity is
      another cause of early kidney allograft dysfunction. OBJECTIVE: To evaluate early
      kidney allograft function in patients who received low-dose CsA therapy for 48
      hours before transplant surgery for comparison with that in recipients who
      received CsA therapy after improvement in allograft function. PATIENTS AND
      METHODS: In a case-control comparative study, 66 kidney recipients were divided
      into 2 groups on the basis of time of initiation of CsA therapy. In group 1,
      patients received CsA, 100 mg twice a day, for 48 hours before surgery, and in
      group 2, patients received CsA therapy after surgery when allograft function had
      improved (serum creatinine concentration <or=3 mg/dL). Other immunosuppression
      medications were the same in both groups. Statistical analysis was performed to
      compare kidney allograft function in the first month posttransplantation.
      RESULTS: In group 1 vs group 2, at day 1 posttransplantation, mean (SD) blood
      urea concentration was 73.72 (31.00) mg/dL vs 87.52 (29.82) mg/dL, serum
      creatinine concentration was 5.11 (1.83) mg/dL vs 6.42 (3.64) mg/dL, and urine
      volume in 24 hours was 11,052 (4290) mL vs 9629 (45.30) mL. At the end of the
      study, blood urea concentration was 49.61 (12.18) mg/dL vs 69.11 (33.76) mg/dL,
      serum creatinine concentration was 1.22 (0.28) mg/dL vs 1.47 (0.79) mg/dL, and
      urine volume in 24 hours was 3202 (986) mL vs 3095 (726) mL. No significant
      difference was noted between the 2 groups for age, sex, and immunosuppression
      medications. CONCLUSION: Low-dose CsA therapy before transplant surgery preserves
      early allograft function without deleterious effects.

PMID- 19765428
TI  - Is screening for IgG antibody to cytomegalovirus and Epstein-Barr virus
      infections mandatory in potential renal transplant recipients and donors in Iran?
AB  - OBJECTIVE: Cytomegalovirus (CMV) and/or Epstein-Barr virus (EBV) infections in
      renal transplant recipients may cause significant morbidity and mortality. To
      manage these infections, established guidelines suggest that both the recipient
      and the donor be routinely tested for anti-CMV and anti-EBV antibodies prior to
      renal transplantation. The aim of this study was to assess the value of screening
      among people living in Iran. PATIENTS AND METHODS: We retrospectively analyzed
      the incidences of CMV and EBV infections among 925 and 710 potential renal
      allograft donors and recipients, respectively, between 2005 and 2008. All cases
      were first transplantations. Enzyme-linked immunosorbent assays (ELISA) were
      performed to determine whether there were antibodies to CMV (IgG) or EBV viral
      capsid antigen (VCAIgG). Finally, we analyzed the seroprevalence and demographic
      factors. RESULTS: Five hundred sixty-eight (61.40%) potential renal transplant
      donors and 483 (68.02%) potential renal transplant recipients were men. Donor
      ages ranged from 18 to 50 years (mean +/- SD, 34.7 +/- 8.1 years) and recipient
      ages ranged from 18 to 60 years (mean +/- SD, 45.9 +/- 7.3 years). Pretransplant
      CMV (IgG) and EBV (VCAIgG) seroprevalence was 100% among all donor, and recipient
      ages and sexes. CONCLUSION: Our findings suggested that kidney transplant centers
      in Iran do not need to perform routine screening for IgG antibodies to CMV and
      EBV among renal transplant recipients and donors of ages >or=18 years.

PMID- 19765429
TI  - Preemptive living donor renal transplantation: a single-center experience.
AB  - Renal transplantation is considered preemptive if it occurs before initiation of
      dialysis. In our experience and in the literature, preemptive transplantation has
      been shown not only to reduce the costs of renal replacement therapy but also to
      avoid the long-term adverse effects of dialysis. Preemptive renal transplantation
      therefore is associated with better survival of both the allograft and the
      recipient. Our aim was to evaluate the outcomes of preemptive renal
      transplantation experience at our center. Since 1985, 1385 renal transplantations
      have been performed at our center. We retrospectively analyzed the 16/1385
      recipients (11 male, 5 female) of overall mean age of 28.5 +/- 15 years who
      underwent preemptive procedures. The causes of end-stage renal failure were focal
      segmental glomerulosclerosis (n = 5), vesicular ureteral reflux (n = 4), Berger
      disease (n = 2), polycystic renal disease (n = 2), and others (n = 3). Ten
      patients were adults, the remaining six, children. The mean creatinine clearance
      and plasma creatinine levels of the recipients before renal transplantation were
      13.5 +/- 8.5 mL/min and 6.7 +/- 2.4 mg/dL, respectively. All renal
      transplantations were performed from living related donors. The mean preoperative
      serum creatinine levels, mean glomerular filtration rate, and creatinine
      clearance rates of the donors were 0.8 +/- 0.1 mg/dL, 61.6 +/- 6.5 mL/min, and
      112.5 12 mL/min, respectively. Two episodes of acute cellular rejection and one
      of humoral rejection occurred during a mean follow-up of 48.7 +/- 14 months
      (range = 25-76 months). The two patients who experienced graft losses due to
      humoral rejection or chronic rejection were retransplanted 2 and 48 months
      thereafter, respectively. At this time all patients are alive with good renal
      function. In conclusion, our single-center results are promising for preemptive
      renal transplantation as the optimal, least-expensive mode of treatment for end
      stage renal disease.

PMID- 19765430
TI  - The outcome of induction therapy with monoclonal antibodies in kidney
      transplantation among Iranian patients: a prospective study.
AB  - INTRODUCTION: The administration of interlukin-2 receptor antagonists for
      induction therapy has reduced the incidence of acute rejection episodes in kidney
      transplantation. Although some studies have investigated the efficacy of these
      monoclonal antibodies, there is little experience among Iranian kidney transplant
      recipients. MATERIALS AND METHODS: Forty-three patients randomly divided into 2
      groups were prospectively followed for 3.4 years. Eighteen patients received 2
      doses of basiliximab (group I) and another 25 patients received 5 doses of
      daclizumab (group II). The posttransplantation complications, last serum
      creatinine level, as well as graft and patient survival rates were compared to
      investigate the efficacy of these therapies. RESULTS: Among 43 patients, 11.6%
      experienced acute rejection episodes: 22.2% in group I and 4% in group II (P >
      .05). In this study, 4.6% of recipients underwent graft nephrectomy: 11.1% in
      group I and 4% in group II (P > .05). The mortality rate was 4.6%: 5.5% in group
      I and 4% in group II (P > .05). The mean serum creatinine level was 1.47 +/- 0.7
      mg/dL. Although it was lower in group I, the difference was not significant. The
      1-year graft and patient survival rates were 90.6% and 95.3%, respectively, with
      no significant differences between the groups. DISCUSSION: Although induction
      therapy with monoclonal antibodies may reduce the incidence of acute rejection
      episodes, graft and patient survival rates were unchanged compared with
      conventional therapies. Also, there were no significant differences between the
      results of induction therapy with basiliximab and daclizumab.

PMID- 19765431
TI  - Living or deceased donor kidney transplantation: a comparison of results and
      survival rates among Iranian patients.
AB  - OBJECTIVE: Kidney transplantation is the selective treatment of end-stage renal
      disease. Although most previous studies have concluded that living kidney
      donation achieves better graft survival, some factors may limit this type of
      donation. This study investigated the survival rates of living and deceased donor
      kidney transplantations among Iranian patients. MATERIALS AND METHODS: The
      records of kidney transplantations up to year 2005 were used to compare 50
      deceased (group I) with 50 living donor transplants (group II). The recipients
      were matched by transplantation time. We used SPSS version 15 software to analyze
      the data. RESULTS: Group I patients included 28 males and 22 females of mean age
      of 38 +/- 13 years, while 26 males and 24 females in group II had a mean age of
      34.6 +/- 14 years. The rejection and graft nephrectomy rates were significantly
      higher among group I than group II (P = .01, P = .02). The first-year graft
      survival was higher in group II (P = .001). The graft survival was significantly
      lower in recipients who needed a biopsy or dialysis (P = .006 and P = .02,
      respectively) and higher among those who had a urine volume >4200 mL within the
      first 24 hours after transplantation (P = .003). Patient survivals were not
      significantly different between the groups. CONCLUSION: Living donor kidney
      transplantations showed higher graft survival and lower acute rejection rates
      compared with those from deceased donors.

PMID- 19765432
TI  - Cadaveric renal transplantation: a single-center experience.
AB  - INTRODUCTION: Renal transplantation remains the treatment of choice for end-stage
      renal disease (ESRD) in regard to patient survival. Iran was one of the first
      countries in the Middle East that began renal transplantation. METHODS: In a
      follow-up study, we enrolled all of our cadaveric renal transplant recipients
      from 2001 to 2007, namely, 39 cases. Related variables collected through
      checklists were entered into SPSS software version 16 and analyzed using the
      Kaplan-Meier method and by descriptive statistics. RESULTS: The mean age of the
      recipients was 35.18 +/- 14.27 years. Twenty-one patients (53.8%) were men. The
      underlying disease for development of ESRD was diabetes (7 cases, 21.2%),
      hypertension (24.2%), glomerulopathies (36.4%), polycystic disease (PKD; 2.6%),
      and 5 (15.2%) were unknown. Four recipients (10.3%) were hospitalized again
      because of acute tubular necrosis after transplantation. An acute rejection
      episode was diagnosed in 7 (17.9%) graft recipients. Surgical complications after
      transplantation were as follows: urinoma, lymphocele, and surgical site leakage
      (each 1 case). One-year patient survival rate was 89.7% in this study; 4
      recipients died within 1-9 months after transplantation. Death-censored 1-year
      graft survival rate was 100%. DISCUSSION: The survival rate of cadaveric
      transplant was in an acceptable range.

PMID- 19765433
TI  - Impact of slow and delayed graft function on kidney graft survival between
      various subgroups among renal transplant patients.
AB  - OBJECTIVE: Renal allografts with excellent graft function show good long-term
      outcomes, while grafts with delayed function have been associated with poor long
      term survivals, although few reports have analyzed outcomes among these groups.
      We compared first-week postoperative graft function among renal transplant
      patients to analyze the impact of slow graft function (SGF) and delayed graft
      function (DGF) on graft survival. MATERIALS AND METHODS: Renal transplantations
      were performed from 362 unrelated, 46 related, and 163 deceased donors. Kidney
      transplant patients were divided into 3 groups according to their initial graft
      function. First-week dialyzed patients formed the DGF group. Nondialyzed patients
      were divided into a SGF or an excellent graft function (EGF) cohort according to
      whether the serum creatinine at day 7 was higher vs lower than 2.5 mg/dL,
      respectively. RESULTS: Of the 570 renal transplant recipients, DGF was observed
      in 39 patients (6.8%), SGF in 64 (11.2%), and EGF in 467 (81.8%). There was no
      significant difference in SGF vs DGF between patients who received kidneys from
      unrelated vs related living or deceased donors. Graft survival was worse among
      the DGF than the SGF or EGF patients, with no significant difference between the
      last 2 groups. The 6-month graft survivals were 74%, 93%, and 96%; the 3-year
      graft survivals were 70%, 88%, and 90%, respectively (P < .001). CONCLUSIONS: We
      observed a similar impact of EGF and SGF on kidney graft survival. Kidney
      transplant recipients who developed DGF showed worse graft survival than those
      with EGF or SGF.

PMID- 19765434
TI  - Kidney transplantation during autoimmune diseases.
AB  - Herein, we report the results of kidney transplantation in 9 of 376 patients who
      underwent kidney transplantation at our center between 1986 and 2007 because of
      chronic renal failure associated with autoimmune disease. Four of the 9 patients
      had systemic lupus erythematosus, 3 had Wegener granulomatosis, and 2 had
      Goodpasture syndrome. Six patients received organs from living donors, and 3
      received cadaver organs. Infections were frequent and included cytomegalovirus
      and urinary tract infection in most cases. There was no difference in occurrence
      of metabolic and cardiovascular complications in our study patients compared with
      other transplant recipients. Incidence of allograft loss (n = 1) was similar to
      that in our entire transplantation population, with an overall rate of 2.9%. We
      conclude that kidney transplantation is a reasonable therapeutic option in
      patients with autoimmune disease with end-stage renal disease because of good
      graft and patient survival compared with kidney recipients without autoimmune
      diseases.

PMID- 19765435
TI  - Early sirolimus therapy in renal transplant recipients at high risk: is it
      justified?
AB  - BACKGROUND: We studied early sirolimus (SRL) therapy in renal transplant
      recipients at high risk after administration of antithymocyte globulin or
      interleukin-2 receptor blockade induction. PATIENTS AND METHODS: In 45 patients,
      SRL therapy was started within 1 month after transplantation. The primary
      indications for conversion of treatment from calcineurin inhibitors (CNIs)
      mycophenolate mofetil (MMF)-steroid to SRL-MMF-steroid were biopsy-proved
      rejection (after treatment), CNI toxicity, CNI elimination, and acute tubular
      necrosis. Pediatric, geriatric, and other patients with medical comorbidities
      were not excluded. RESULTS: Post-SRL rejection episodes were reported in 22.2% of
      recipients including 15.6% who were resistant to steroid therapy. Mean (SD)
      follow-up after SRL therapy was 59.9 (8.1) months. Proteinuria greater than 2 g/d
      (P = .001), leukopenia (P < .001), hyperlipidemia (P < .001), and transaminases
      values (P = .02) increased significantly after SRL therapy. Graft survival was
      88.8%, and patient survival was 93.3%. There was significant improvement in serum
      creatinine concentration and estimated creatinine clearance by the end of the
      study (P < .001). A high incidence of adverse effects and infections was noted
      post-SRL therapy, and the drug was discontinued in 31% of patients because of
      multiple adverse effects. At multivariate analysis, age, hypertension,
      nutritional status, bone marrow suppression, hyperlipidemia, and graft
      dysfunction were identified as risk factors for worse graft and patient outcome.
      CONCLUSION: Early treatment with combined SRL-MMF-steroid may be effective as a
      CNI-free immunosuppression regimen in patients at high risk; however, there is a
      high rate of adverse effects during long-term follow-up.

PMID- 19765436
TI  - Conversion to sirolimus for chronic allograft nephropathy and calcineurin
      inhibitor toxicity and the adverse effects of sirolimus after conversion.
AB  - BACKGROUND: Chronic allograft nephropathy and calcineurin inhibitor toxicity may
      cause graft loss. After kidney transplantation, especially among those patients
      with chronic allograft nephropathy, sirolimus may be a good alternative to
      calcineurin inhibitors. Unlike calcineurin inhibitors, sirolimus is devoid of
      significant nephrotoxicity, but approximately 30% to 50% of patients on sirolimus
      therapy display mild or severe adverse effects. We sought to report our
      experience with sirolimus conversion among patients with chronic allograft
      nephropathy as well as the mild versus severe adverse effects that limit the
      drug's use. MATERIALS AND METHODS: We analyzed the outcomes of 88 patients (64
      men and 24 women) of overall mean age of 35.9 +/- 9.9 years (range, 21-59 years)
      who had undergone kidney transplantation. Immunosuppressive therapy had been
      converted from a calcineurin inhibitor to sirolimus because of biopsy-proven
      chronic allograft nephropathy, calcineurin inhibitor toxicity, or presence of
      malignancy. We excluded patients with prior acute rejection episodes. Subjects
      were divided into two groups with respect to their creatinine levels: Group A < 2
      mg/dL and Group B >or= 2 mg/dL. After conversion to sirolimus, possible adverse
      effects of sirolimus were evaluated at the follow-up inset. Each patient
      underwent a physical examination, and estimation of serum lipid and electrolyte
      levels as well as hemoglobin concentration. RESULTS: At the time of conversion of
      the 88 renal transplant patients, their mean duration after grafting was 48 +/-
      15 months (range, 4-296). The prior treatment consisted of a calcineurin
      inhibitor, prednisolone, and mycophenolate mofetil. After conversion, the
      calcineurin inhibitor was stopped and sirolimus was begun. The 48 Group 2
      patients (34 men, 14 women) of overall mean posttransplant time of 22.7 +/- 14.6
      months who underwent conversion displayed a mean serum creatinine increase to 3.2
      +/- 1.4 mg/dL, including 17 subjects who underwent rejection. The 40 Group 1
      patients (30 men, 10 women) with a mean overall posttransplant period of 67.6 +/-
      49.9 months showed an fall in serum creatinine level to 1.4 +/- 0.5 mg/dL among
      only 3 patients. While 5/88 patients showed no increase in proteinuria (5.6%); 83
      (94.4%) did experience it. Proteinuria increased from a mean of 192 +/- 316 to
      449 +/- 422 mg/d. Only three patients displayed heavy proteinuria (>3 g/d);
      sirolimus was discontinued for this reason. Proteinuria was well controlled in
      the other patients with angiotensin-converting enzyme and/or angiotensin II
      receptor inhibitor agents. After sirolimus conversion, serum cholesterol levels
      increased from 187 +/- 42 to 214 +/- 52 mg/dL, and serum triglyceride levels
      increased from 161 +/- 61 to 194 +/- 102 mg/dL. All but four patients responded
      to statin therapy, with serum lipid levels falling to acceptable levels. Another
      four patients developed unilateral lower extremity edema with sirolimus
      discontinued for this reason. One patient displayed generalized arthralgia.
      CONCLUSION: Chronic allograft nephropathy or calcineurin inhibitor toxicity can
      lead to loss of graft kidney function. Calcineurin inhibitor toxicity can lead to
      chronic allograft nephropathy. Patients with a low baseline serum creatinine
      level who undergo sirolimus conversion showed stabilized kidney function. Late
      conversion of patients with a serum creatinine above 2 mg/dL face a risk of graft
      failure. Sirolimus displayed a limited incidence of serious adverse effects; mild
      or moderate adverse effects, such as hyperlipidemia and proteinuria, were easily
      controlled with countermeasure therapy.

PMID- 19765437
TI  - Could prophylactic monoclonal antibody improve kidney graft survival?
AB  - OBJECTIVES: This study was designed to evaluate the impact of daclizumab
      monoclonal antibody on early and late kidney graft survival. MATERIALS AND
      METHODS: From 2007 to 2008, 57 kidney transplant recipients were followed for a
      mean of 9.3 months. Twenty-three patients received 1 mg/kg daclizumab 24 hours
      before and 14 days after transplantation. In contrast, 34 patients (controls) did
      not receive daclizumab. The same immunosuppressive protocol was administered to
      all participants: oral prednisolone, mycophenolate mofetil, and cyclosporine.
      Delayed graft function (DGF), acute rejection, prednisolone pulses and/or
      antithymoglobulin (ATG), cytomegalovirus (CMV) infection, urinary tract infection
      (UTI), as well as early and late graft function were compared between the two
      groups. RESULTS: The mean age in cases and controls was 39.7 and 37.1 years,
      respectively. The occurrence of DGF was 4% versus 3%; reversible acute rejection,
      16% versus 14.5%, and irreversible acute rejection 0% versus 9% (P < .05) for
      treated versus control groups, respectively. ATG was used in 21% versus 23%, and
      pulse prednisolone 26% versus 20%, respectively. In case and control groups, the
      mean creatinine levels were 1.4 mg/dL versus 1.35 mg/dL at discharge. At last
      follow-up, it was 1.35 mg/dL versus 1.2 mg/dL, respectively. CMV infection
      occurred in 30% versus 35%, and UTI in 17% versus 19% of treated versus controls,
      respectively. CONCLUSION: The prophylactic administration of daclizumab improved
      early graft survival and prevented irreversible acute rejection.

PMID- 19765438
TI  - Mycophenolate mofetil dose reduction in renal transplant recipients: a 5-year
      follow-up study.
AB  - OBJECTIVE: Mycophenolate mofetil (MMF), an immunosuppressant that is widely used
      in renal transplantation, is associated with several dose-dependent hematologic
      and gastrointestinal side effects that may require dose reduction or even
      discontinuation. The aim of this study was to compare renal allograft function
      and acute rejection episodes among kidney allograft recipients who were on 2
      regimens of MMF for at least 5 years. MATERIALS AND METHODS: This prospective
      cohort of 55 kidney allograft recipients was followed for deterioration of
      allograft function, evidence of acute rejection, and allograft survival. Twenty
      two patients (40%) underwent MMF dose reduction to 1.35 to 0.23 g/d due to
      perceived side effects or economic reasons (group 1). The mean time for this
      change was 4.2 +/- 2.1 months after kidney transplantation. The remaining
      patients (group 2, n = 33) were continued on MMF (2 g/d). All patients were
      followed for at least 5 years after transplantation. Renal function tests (blood
      urea and serum creatinine) were measured monthly for 2 years and then every 2
      months. Statistical analysis was performed using SPSS 11.0 (Student t test). P
      <or= .05 was considered significant. RESULTS: The 2 groups were comparable
      regarding age, gender, and immunosuppressive medications. The renal function
      tests were comparable at the end of the study. Mean blood urea values were 44.8
      +/- 5.8 and 46.8 +/- 6.8 mg/dL in groups 1 and 2 (P > .05); mean serum creatinine
      values were 1.32 +/- 0.14 and 1.38 +/- 0.21 mg/dL, respectively (P > .05). There
      were 2 graft losses and 1 patient loss in group 2. There were also 2 graft losses
      among group 1 patients. CONCLUSION: Our study showed that MMF dose reduction was
      not associated with an increased risk of acute renal allograft rejection or
      impaired allograft function at 5 years.

PMID- 19765439
TI  - TH1/TH2 cytokines and soluble CD30 levels in kidney allograft patients with donor
      bone marrow cell infusion.
AB  - OBJECTIVE: We investigated the relevance of donor bone marrow cell infusion
      (DBMI) and serum levels of interferon-gamma (IFN-gamma), interleukin-10 (IL-10),
      and soluble CD30 (sCD30) in kidney recipients. PATIENTS AND METHODS: We analyzed
      the allograft outcomes correlated with sCD30, IFN-gamma, and IL-10 levels using
      pre- and posttransplantation sera from 40 live donor renal transplants (20
      patients with DBMI [2.1 x 10(9) +/- 1.3 x 10(9) mononuclear cells/body] and 20
      controls). RESULTS: Patients with acute rejection episodes (ARE)-3/20 DBMI and
      6/20 controls-showed increased sCD30 and IFN-gamma as well as decreased IL-10
      posttransplantation compared with nonrejectors. Significant differences were
      observed for sCD30 and IFN-gamma levels: 59.54 vs 30.92 ng/mL (P = .02) and 11.91
      vs 3.01 pg/mL (P = .01), respectively. Comparison of pre- and posttransplant
      levels of IFN-gamma, IL-10, and sCD30 in ARE patients showed higher levels in
      posttransplant sera except for IFN-gamma in controls (6.37 vs 11.93; P = .01).
      Increased IFN-gamma and IL-10 were correlated with rejection (r = .93; P = .008).
      sCD30 correlated with serum creatinine among ARE patients in control and DBMI
      groups (r = .89; P = .019; and r = 1.00; P < .0001, respectively). CONCLUSIONS:
      Higher levels of sCD30, IFN-gamma, and IL-10 posttransplantation in rejecting
      patients provided evidence for coexistence of cellular and humoral responses in
      ARE. There appeared to be a down-regulatory effect of infusion on alloresponses.

PMID- 19765440
TI  - Role of resistive index measurement in diagnosis of acute rejection episodes
      following successful kidney transplantation.
AB  - OBJECTIVE: This study was performed to evaluate the role of resistive index (RI)
      in the diagnosis of rejection episodes following successful kidney
      transplantation. MATERIALS AND METHODS: One hundred and one unrelated living
      first kidney allograft adult recipients (75 males and 26 females) of overall mean
      age of 39 years were enrolled and prospectively followed for 6 months. The
      measurement of RI by Doppler ultrasonography was performed in all patients on
      days 3 and 7 as well as at months 1, 3, and 6 in addition to when there was graft
      dysfunction. We determined serum creatinine and cyclosporine levels. RESULTS:
      Twenty-seven patients (26.7%) experienced 33 acute rejection episodes during the
      follow-up. There were significant differences between mean RI among patients with
      normal function vs rejection: 0.606 +/- 0.065 vs 0.866 +/- 0.083 (P < .05),
      respectively. Overall, elevated levels of cyclosporine, ischemic acute tubular
      necrosis (ATN), and renal artery thrombosis were observed in 8, 5, and 3
      patients, respectively. No association was observed between these factors and RI.
      CONCLUSIONS: RI was significantly higher in patients with acute rejection
      episodes. It had no association with ATN or cyclosporine toxicity. Hence, RI may
      be useful to diagnose acute renal allograft rejection following renal
      transplantation.

PMID- 19765441
TI  - Metabolic syndrome is related to long-term graft function in renal transplant
      recipients.
AB  - The metabolic syndrome (MS) is a known cardiovascular risk factor in the general
      population and a common problem among renal transplant recipients. This study
      investigated whether MS after renal transplantation affected long-term graft
      function. We included 112 transplants at our center between 2000 and 2002. We
      excluded patients with the presence of pretransplant diabetes or nonstable renal
      function at 1 year after transplantation. We evaluated parameters such as
      demographic features, medications, smoking history, body mass index, daily
      proteinuria, blood pressure, number of HLA mismatches, number of acute rejection
      episodes, delayed graft function, and laboratory parameters. Patients were
      followed for a mean of 69.86 +/- 21.94 months. The prevalence of MS was
      determined using the National Cholesterol Education Program-Adult Treatment Panel
      III criteria. At 1 year after transplant, 28.6% of subjects had MS, whereas only
      10.7% had MS before transplantation. Among 27.7% of patients graft failure had
      occurred during the follow-up; MS was more frequent among these individuals
      compared with those displaying stable renal function (51.6% vs 19.8%; P = .002).
      Older donor age, delayed graft function, acute rejection episodes, smoking
      history, MS, proteinuria, serum creatinine level, and C-reactive protein were
      associated with graft failure. Upon multivariate Cox regression analysis,
      patients with MS at 1 year after transplantation showed an increased risk for
      graft failure (relative risk, 0.22; 95% confidence interval, 0.06-0.75; P =
      .016). Older donor age and proteinuria level were other independent risk factors
      for graft failure. The MS was a prominent risk factor for graft failure. Because
      MS is a cluster of modifiable risk factors, early identification of patients at
      risk and intervention in due time may improve graft survival.

PMID- 19765442
TI  - Posttransplant diabetes mellitus: incidence and risk factors.
AB  - OBJECTIVE: Posttransplant diabetes mellitus (PTDM) is a common and serious
      complication of renal transplantation. Estimates of the incidence of PTDM after
      renal transplantation vary between 2% and 54%. The aim of the present study was
      to evaluate the incidence and risk factors for PTDM among our renal transplant
      patients. PATIENTS AND METHODS: In this study we evaluated 121 nondiabetic
      patients with end-stage renal disease (ESRD) who underwent kidney transplantation
      for the first time at our centers since 2005. All patients received the same
      protocol of immunosuppressive therapy. PTDM was defined according to the clinical
      practice recommendations of the American Diabetes Association. RESULTS: At 12
      months following renal transplantation, 9.9% of patients developed PTDM. Patients
      with PTDM were significantly older (P = .013) and had higher body mass index (P =
      .001). There were significant differences (P <or= .05) between PTDM and non-PTDM
      patients with respect to systolic blood pressure, serum triglycerides (TG),
      peritoneal dialysis as renal replacement therapy before transplantation, and
      duration of pretransplant dialysis therapy. Upon multivariate analysis, serum TG,
      systolic blood pressure, and body mass index were associated with PTDM (P <or=
      .05). CONCLUSIONS: The incidence at 12 months of PTDM among our renal transplant
      recipients was 9.9%. The most important factors associated with PTDM were serum
      TG, systolic blood pressure, and body mass index.

PMID- 19765443
TI  - Frequency and risk factors for posttransplant diabetes mellitus in Iranian renal
      transplant patients.
AB  - Posttransplant diabetes mellitus (PTDM) is a frequent complication of renal
      transplantation. This study was performed to determine the prevalence of and risk
      factors for PTDM among Iranian renal transplant recipients. In this cross
      sectional study, 300 patients were studied in 2007. It included questionnaires
      with clinical data and blood samples. PTDM was defined as DM without a
      pretransplant history. The 184 (61.3%) male and 116 (38.7%) female patients of
      overall mean age of 41.2 +/- 13.5 years were 67.4 +/- 48.6 months after the
      procedure. PTDM was observed in 24 patients (8%). The mean interval to develop
      PTDM was 19.9 +/- 31.5 months. The mean age of PTDM patients was significantly
      higher than non-PTDM patients: 49.4 +/- 13.4 vs 40.6 +/- 13.4 years (P < .005).
      The mean serum high-density lipoprotein (HDL) was higher among PTDM compared with
      non-PTDM patients: 71.4 +/- 21 vs 58.6 +/- 14.6 (P < .005). There was a trend
      toward higher serum low-density lipoprotein (LDL) among PTDM patients: 109.2 +/-
      29.5 vs 96.2 +/- 25.2 (P = .06). A recent admission was more frequent among PTDM
      patients (58.3% vs 28.7%; P < .005), as was history of hepatitis C virus (HCV)
      infection (6% vs 1%; P < .01). There was no significant difference in doses of
      immunosuppressive drugs and doses atenolol, mean body mass index, DM family
      history, rejection, cytomegalovirus (CMV) infection, or frequency of positive
      anti-HCV antibody between the 2 groups. Our study showed an 8% prevalence of
      PTDM. Mean age, history of recent admissions and HCV infection, as well as mean
      plasma HDL and LDL levels were higher among PTDM patients.

PMID- 19765444
TI  - Insulin resistance and insulin secretion changes in kidney transplant recipients
      with normal graft function compared with those with delayed graft function early
      after transplantation.
AB  - INTRODUCTION: We compared insulin resistance (IR) and insulin secretion (IS)
      among kidney transplant recipients with normal versus delayed graft function
      (DGF) early after transplantation. METHODS: We selected 55 kidney transplant
      recipients without a history of clinical diabetes mellitus. The basal values of
      glucose (G) and insulin (I) were used to calculate indices of IR and IS before,
      on the third day, as well as at the end of the first, second, and third weeks
      after transplantation. RESULTS: Before transplantation IR was more prevalent
      (62.5%) than impaired IS (20%; P = .012). Three weeks after engraftment, IR was
      significantly reduced (P < .001), whereas the reduction in the IS was not
      significant (P = .17). Splitting the results between normal and delayed
      functioning grafts showed a significant difference in both IR and IS between the
      2 groups on the third day after transplantation (P = .018 and .024,
      respectively). Regression models showed that only cumulative administered
      cyclosporine dose and plasma creatinine were significantly (or near
      significantly) associated with IR (P = .04 and .07, respectively). CONCLUSION:
      Among patients with DGF there was a significantly greater prevalence of IR and IS
      compared with successfully engrafted patients in the middle of the first week
      after transplantation. With resumption of normal kidney function among the DGF
      group, this difference disappeared at the end of the third week after
      transplantation.

PMID- 19765445
TI  - Osteoporosis and related risk factors in renal transplant recipients.
AB  - Decreased bone mineral density is a common problem after kidney transplantation.
      Osteoporosis has a major role in morbidity in these patients. We evaluated the
      incidence of osteoporosis and determined risk factors in 77 patients aged 17 to
      50 years who had undergone renal transplantation 6 months to 2 years previously.
      Bone mineral densitometry was performed using dual-energy x-ray absorptiometry.
      The incidence of osteoporosis was 26% (20 of 77 patients). Mean (SD) age of
      affected patients was 34.6 (8.7) years. The most common sites of osteoporosis
      were the hip (osteoporotic in 19 patients [24.7%] and osteopenic in 42 [54.5%])
      and the spine (osteoporotic in 6 patients [7.8%] and osteopenic in 52 [67.5%]).
      There was a significant relationship between posttransplantation creatinine
      concentration and hip osteoporosis (P = .01). No relationship was observed
      between osteoporosis and age, sex, body mass index, duration of hemodialysis
      therapy, cumulative dosage of any drugs, or use of pulsed methylprednisolone
      therapy. A hip or spine z score of 1 or less had no relationship to the number of
      steroid pulse sessions but was significantly related to the total dosage of
      cyclosporine (P < .001), prednisolone (P < .001), and mycophenolate mofetil (P <
      .05). A hip z score of less than 1 was related to the posttransplantation period
      (P = .02). In conclusion, osteoporosis is a frequent complication that requires
      detection and treatment to reduce morbidity.

PMID- 19765446
TI  - Vitamin D status, bone mineral density, and inflammation in kidney
      transplantation patients.
AB  - Vitamin D has immunomodulatory and anti-inflammatory activities in the healthy
      population and in various disease states. There are few data on the
      quantification of vitamin D status and inflammation with respect to changes in
      bone mineral density among renal transplantation patients. We analyzed the
      influence of vitamin D levels on allograft function and inflammatory status at
      the time of enrollment and at 1-year follow-up. Sixty-four renal transplant
      patients, including 38 males, showed an overall age of 38.61 +/- 1.05 years, had
      a mean graft age of 6.15 +/- 3.17 years. We excluded patients who had diabetes
      mellitus, chronic inflammatory disease, or chronic allograft nephropathy. We
      obtained pre- and posttransplantation serum samples and daily proteinuria on each
      patient. Measurements of bone mineral density were performed by dual-energy X-ray
      absortiometry. After enrollment, we followed the patients for 1 year. Thereafter
      we assessed serum creatinine, C-reactive protein, albumin, and spot urinary
      protein levels. The patients were divided into two groups based upon vitamin D
      levels: group I (n = 29), <20 microg/L versus group II (n = 35), >or=20 microg/L.
      There was no significant difference in intact parathyroid hormone levels between
      the two groups. Vitamin D level positively correlated with serum creatinine (r =
      .32, P = .01) and serum albumin levels (r = .28, P = .023) at the time of
      enrollment. At 1 year, patients in group I showed significantly higher creatinine
      (P < .001) and proteinuria levels (P < .05) than those in group II. Low vitamin D
      levels are not uncommon among renal transplant recipients. There was a
      significant association of vitamin D levels with renal allograft function. Low
      vitamin D levels may be a predictor of worsening of graft function and increasing
      proteinuria.

PMID- 19765447
TI  - Relationship between serum homocysteine and other parameters in renal transplant
      patients.
AB  - INTRODUCTION: Hyperhomocysteinemia frequently occurs after renal transplantation.
      We therefore assessed whether serum homocysteine (Hcy) concentrations were
      correlated with clinical, paraclinical, and arterial Doppler parameters among
      renal transplant patients. METHODS: A cross-sectional study was performed on 47
      patients (30 males, 17 females) who received unrelated living donor renal
      transplants. RESULTS: The mean serum Hcy concentration was 21.7 +/- 8.4
      micromol/L (range = 5.8-48 micromol/L); 37 patients (79%) showed
      hyperhomocysteinemia (Hcy >or= 15 micromol/L). Serum Hcy was strongly related to
      body mass index (BMI; r = .43, P = .002), cyclosporine trough level (r = .44, P =
      .005), and serum creatinine concentration (r = .32, P = .028), but not to age,
      transplant duration, or sex. Multivariate analysis showed that only BMI (P =
      .003) and cyclosporine trough level (P = .0037) were independent predictors of
      serum Hcy concentrations. Hyperhomocysteinemia was more prevalent among patients
      taking mycophenolate mofetil (MMF) than azathioprine (86% vs 50%; P = 0.017). The
      hyperhomocysteinemia and normohomocysteinemia groups did not differ significantly
      in mean carotid intima-media thickness (IMT; 0.78 +/- 0.348 vs 0.77 +/- 0.419 mm,
      P = .97) or mean intrarenal resistive index (RI) (0.7 +/- 0.06 vs 0.7 +/- 0.06, P
      = .85). The two groups also did not differ in sex prevalence, diabetes, C
      reactive protein >or= 5 mg/L, or mean low-density lipoprotein, high-density
      lipoprotein, and mean arterial pressure (MAP) values. CONCLUSION: Serum Hcy
      correlated with higher cyclosporine trough levels and obesity.
      Hyperhomocysteinemia was more common among patients taking MMF than azathioprine,
      but had no effect on intrarenal RI or carotid IMT.

PMID- 19765448
TI  - Effect of renal transplantation on coronary artery calcification in hemodialysis
      patients.
AB  - OBJECTIVE: Vascular calcification is a strong predictor of cardiovascular and all
      cause mortality. Coronary artery calcification is more frequent, more extensive,
      and progresses more rapidly among subjects with chronic kidney disease (CKD) than
      in the general population. It is also considered to be a marker of coronary heart
      disease, the main cause of increased morbidity and mortality among patients
      either on maintenance hemodialysis or after transplantation. The aim of this
      study was to evaluate the effect of renal transplantation on the calcium scores
      of coronary arteries among hemodialysis patients. PATIENTS AND METHODS: The study
      included 31 patients (17 males and 14 females) of age range 19 to 56 years (mean,
      38.08 +/- 13.49 years) who had been hemodialyzed 3 times a week for 6 to 49
      months (mean, 20 +/- 15.72 months) prior to renal transplantation. Homocysteine,
      intact parathyroid hormone (iPTH), calcium, phosphate, and indices of lipid
      metabolism such as total cholesterol, high-density lipoprotein (HDL), low-density
      lipoprotein (LDL), and triglycerides were measured before and at 6 months after
      transplantation. To evaluate coronary artery calcification, all patients
      underwent multidetector coronary computed tomography (MDCT) using the Agatston
      technique for calcium scoring (CS) and color Doppler ultrasound for IMT before
      and at 6 months after the procedure. RESULTS: The prevalence of coronary artery
      calcifications among dialysis patients was 96% with a total CS ranging from 0 to
      198. It affected more than 2 vessels in >50% of subjects with higher calcium
      scores in the left anterior descending artery (LAD). Mean total CS decreased
      significantly from pre- (39.82 +/- 63.05) to postoperation (24.34 +/- 39.55; P <
      .001). CS decreased from pre- to postprocedure in the left main artery (7.4 +/-
      13.03 to 4.3 +/- 8.54; P < .01) and in LAD (15.76 +/- 23.53 to 10.23 +/- 15.81; P
      < .01 and in the circumflex (7.8 +/- 14.98 to 5.1 +/- 9.57; P < .001) and in the
      right coronary artery (9.2 +/- 17.18 to 4.7 +/- 8.18; P < .01). The CS before the
      procedure correlated significantly with age (r = .39; P < .005), P (r = .33; P <
      .05), Ca x P product (r = .39; P < .05), iPTH (r = .43; P < .001), and IMT (r =
      .56; P < .0001). There was a linear, meaningful correlation between CS and iPTH
      and Ca x P product reduction after renal transplantation. CONCLUSIONS: Renal
      transplantation significantly reduced coronary artery calcification among
      dialysis patients. It linearly correlated with a decrease in iPTH and Ca x P
      product at an early period after renal transplantation.

PMID- 19765449
TI  - Effect of angiotensin II type-1 receptor blockers on stable allograft kidneys:
      prospective randomized study.
AB  - OBJECTIVE: Is assess the effects of angiotensin II type-I receptor blockers on
      outcomes in renal transplant recipients without proteinuria or
      posttransplantation erythrocytosis. PATIENTS AND METHODS: Fifty renal transplant
      recipients (30 men and 20 women, with a mean [SD] age of 40 [13] years) were
      randomized into 2 groups of 25 patients each; 1 group was treated with losartan
      for 1 year, and the other was not (control group). Blood pressure and other
      biochemical parameters were measured at baseline and at 6 and 12 months
      posttransplantation. RESULTS: After 1 year, the losartan group had significantly
      lower systolic blood pressure (113 [22] mm Hg vs 126 [18] mm Hg; P = .04) and
      hemoglobin concentration (12.8 [1.9] g/dL vs 14.5 [2.1] g/dL; P = .006) and
      significantly higher serum high-density lipoprotein cholesterol concentration (58
      [22] mg/dL vs 47 [10] mg/dL; P = .03) compared with the control group; however
      the incidence of anemia did not differ (37% vs 20%; P = .20). In the losartan
      group, there were significant changes in hemoglobin concentration between
      baseline and 6 months (14.5 [1.6] g/dL vs 12.9 [1.49] g/dL; P < .001), but not
      between 6 and 12 months (12.9 [1.49] g/dL vs 12.8 [1.96] g/dL; P = .43). After 1
      year, there were no significant between-group differences in diastolic
      hypertension, serum creatinine concentration, creatinine clearance, and serum
      potassium, low-density lipoprotein cholesterol, triglyceride, and uric acid
      concentrations. CONCLUSION: Losartan significantly increased high-density
      lipoprotein concentration and significantly decreased systolic hypertension.
      Although losartan decreased the hemoglobin concentration during the first 6
      months, its effect did not progress with longer use. To determine the effect of
      losartan on renal function, additional studies with longer follow-up are needed.

PMID- 19765450
TI  - Relationship of renal resistive index and cardiovascular disease in renal
      transplant recipients.
AB  - BACKGROUND: Cardiovascular disease is the primary cause of death in renal
      transplant recipients, and elevated renal allograft resistive index (RI) has been
      associated with patient survival. OBJECTIVE: To evaluate the predictive value of
      intrarenal RI on atherosclerotic disease. PATIENTS AND METHODS: Ninety-seven
      patients who had undergone renal transplantation between 1999 and 2001 and had
      stable renal function were included in the study. Patients with renal artery
      stenosis, urinary tract obstruction, clinical symptoms of acute rejection, or
      chronic allograft nephropathy were excluded. Clinical and laboratory information
      was obtained from the medical records and included demographic data, medications
      used, body mass index, blood pressure, and laboratory values. Intrarenal RI and
      carotid intima-media thickness (IMT) were determined using Doppler
      ultrasonography. RESULTS: At linear regression analysis, RI was significantly
      correlated with recipient age, C-reactive protein concentration, systolic blood
      pressure, pulse pressure, body mass index, smoking, and carotid IMT. At
      multivariate linear regression analysis, only pulse pressure was an independent
      predictor of intrarenal RI. CONCLUSION: Intrarenal RI is associated with
      traditional cardiovascular risk factors and carotid IMT. Elevated intrarenal
      graft RI may be predictive of cardiovascular disease in renal transplant
      recipients without complications.

PMID- 19765451
TI  - Hepatic stellate cells in hepatitis C patients: relationship with the development
      of interstitial fibrosis in renal allografts.
AB  - The aim of this study was twofold; first, we evaluated the influence of hepatitis
      C virus (HCV) and iron deposition on hepatic stellate cells (HSCs), and second,
      we determined the influence of HSCs on the development of interstitial fibrosis
      (IF) in renal allografts. Thirty chronic HCV positive patients bearing renal
      allografts underwent liver biopsies, which were scored for iron deposition and
      the number of HSCs. We evaluated the density of tumor necrosis factor-alpha (TNF
      alpha) in liver biopsies and the expression of transforming growth factor-beta
      (TGF-beta) on tubules of renal allografts from the same patients. We examined the
      development of IF in renal allografts at 12 and 24 months after the reference
      biopsy. The density of HSCs was significantly greater among patients with
      compared with those without iron deposits (P < .01). TNF-alpha expression was
      localized mainly to liver sinusoidal cells; in some cases, it was also expressed
      in hepatocytes. Patients with higher-grade TNF-alpha expression in the liver
      showed higher-grade alpha-smooth muscle antibody (alpha-SMA)-positive HSCs (P <
      .001). In parallel, an increasing amount of HSCs in the liver increased the
      incidence of IF in the renal allograft at 12 (P < .01) and 24 (P < .01) months
      after the reference biopsy. In addition, the expression of TGF-beta on renal
      allograft tubules were increased with greater grades of alpha-SMA-positive HSCs
      in liver (P < .01). In conclusion, HCV infection seemed to trigger the
      development of IF in renal allografts by augmenting TGF-beta secretion through
      activation of HSC.

PMID- 19765452
TI  - Cytomegalovirus infection and disease following renal transplantation:
      preliminary report of incidence and potential risk factors.
AB  - BACKGROUND: Cytomegalovirus (CMV) infection and disease are major causes of
      morbidity and mortality after renal transplantation. However, the incidence and
      potential risk factors are different in developing countries. We sought to
      determine the incidence and potential risk factors for CMV infection and disease
      in our center. We also sought to identify groups of recipients who may benefit
      from preemptive therapy. MATERIALS AND METHODS: Forty renal transplant recipients
      were monitored regularly for CMV infection within 6 months after transplantation
      using CMV immunoglobulin (Ig) M and IgG titers, pp65 antigenemia, and CMV DNA by
      polymerase chain reaction (PCR). Thorough laboratory and physical examinations
      were performed to detect CMV disease. We evaluated the role of various factors in
      CMV infection and disease development using Cox regression and Kaplan-Meier
      statistical models. RESULTS: CMV infection and disease were detected in 33
      (82.5%) and 10 (25%) subjects, respectively. Average time to infection and
      disease development was 4.7 and 11 weeks, respectively. PCR was the most accurate
      method of diagnosis in 22 (67%) cases. By comparison to other recipients,
      patients who received antithymocyte globulin (ATG) showed a significant decrease
      in time to disease development (P = .009). Upon multivariate survival analysis,
      ATG therapy remained an independent risk factor for CMV disease (odds ratio: 6.8;
      P = .02). CONCLUSION: Due to the low rate of progression from CMV infection to
      disease, it does not seem reasonable to perform preemptive therapy in all
      infected cases. ATG therapy was an independent risk factor for CMV disease.
      Recipients of this treatment would be proper candidates to receive preemptive
      therapy.

PMID- 19765453
TI  - Upper gastrointestinal bleeding during the first month after renal
      transplantation in the mycophenolate mofetil era.
AB  - Upper gastrointestinal (GI) bleeding remains a significant cause of mortality and
      morbidity among renal transplant recipients. We retrospectively analyzed the
      records of patients who received renal transplantations between January 2001 and
      July 2007 using mycophenolate mofetil (MMF) in their immunosuppressive regimens.
      The following data were recorded for those subjects with upper GI bleeding during
      the first month after transplantation (group B, cases): age, sex, acute rejection
      episodes, pretransplant upper GI endoscopic findings, Helicobacter positivity,
      and cytomegalovirus (CMV) seropositivity. The same parameters were studied among
      a group of patients, who did not have a history of upper GI bleeding (group A,
      controls). A statistical analysis was performed to ascertain potential risk
      factors. Among 523 patients (311 females, 212 males) of age range 7 to 58 years,
      27 (5.2%) had upper GI bleeding: 13 males and 14 females of mean age 44 +/- 12
      years. The most frequent endoscopic finding was erosive gastritis (n = 13; 48.1%)
      followed by duodenal ulcers. Binary logistic regression analysis comparing the 2
      groups showed that acute rejection episodes (P = .015) and active CMV infection
      (P = .046) were the most prominent risk factors for upper GI bleeding during the
      first month after renal transplantation.

PMID- 19765454
TI  - Genitourinary tumor following kidney transplantation: a multicenter study.
AB  - Renal transplantation has been advocated as the treatment of choice for end-stage
      renal disease. Immunosuppression increases the incidence of cancer and promotes
      the growth of neoplasms in solid organ recipients. There have been a few reports
      on the incidence of cancer from transplant registries. It is difficult to
      precisely compare the incidence with that in the general population using data
      from small, single-center studies. Thus, we sought to study the prevalence of
      genitourinary cancer development in Iranian renal transplant recipients. We
      collected data from 5 kidney transplant centers in Iran between 1984 and 2008,
      seeking to detect the incidence, type, and outcome of cancers after kidney
      transplantation. Only histologically confirmed tumors, which occurred after renal
      transplantation, were included in the analysis. Of the 5532 patients who
      underwent kidney transplantation, genitourinary tumors were detected in 21
      subjects (0.38%), namely, 12 males and 9 females. Transitional cell carcinoma
      (TCC) of the bladder, the most common genitourinary cancer (n = 7) was followed
      by renal cell carcinoma (RCC; n = 5), ovarian cancer (n = 3), breast cancer (n =
      3), prostate cancer (n = 1), seminoma (n = 1), and uterine cancer (n = 1). The
      overall mean age of the patients was 46 +/- 12 years (range, 19-72 years) and the
      median time to diagnosis after transplantation was 72 months (range, 4-240
      months). Seven patients died during the follow-up. There was a male predominance
      among TCC of the bladder and RCC (5:2 and 4:1, respectively). In conclusion, TCC
      of the bladder was the most common genitourinary tumor following kidney
      transplantation. It was predominant in male patients.

PMID- 19765455
TI  - Active management of post-renal transplantation BK virus nephropathy: preliminary
      report.
AB  - OBJECTIVE: To assess the efficacy of leflunomide, intravenous immunoglobulins,
      and ciprofloxacin as active treatment of postrenal transplant BK virus
      nephropathy (BKVN) in graft outcome at 1 year. PATIENTS AND METHODS: Renal
      transplant recipients with positive results of 2 BK virus polymerase chain
      reaction tests of urine and blood underwent graft biopsy to confirm BKVN. If BKVN
      was diagnosed, antimetabolite therapy (mycophenolate mofetil or azathioprine) was
      changed to leflunomide therapy accompanied by a course of immunoglobulin and oral
      ciproflxacin. RESULTS: Of 18 patients evaluated, 72% were men. Nine patients
      received cadaveric organs, with a mean of 3.6 HLA mismatches. All patients
      received induction thereapy (61% thymoglobulin), and 61% received antirejection
      therapy before BKVN was diagnosed. Maintenance immunosuppression therapy was
      primarily with prednisolone (94%); mycophenolate mofetil, 2 g/d (94%); and
      tacrolimus (61%). At baseline, mean (SD) creatinine clearance was 35.6 (11.5)
      mL/min/1.73(2), which decreased to 29.3 (17.3) mL/min/1.73(2) at 1 year (P =
      .01). Patients were divided into 2 groups of 9 each according to creatinine
      clearance values. In group 1, baseline value was 44.5 (6.6) mL/min/1.73(2),
      compared with 25.36 (7.8) mL/min/1.73(2) in group 2, which decreased to 42.66
      (12.8) mL/min/1.73(2) (P = .23) and 16.76 (9.0) mL/min/1.73(2) (P = .009),
      respectively, at 1 year. Three grafts (16.7%) were lost by the end of the study,
      all in group 2 (P = .03). CONCLUSION: Late diagnosis and intensive
      immunosuppression predispose to BKVN. Early active treatment of BKVN may improve
      graft outcome at 1 year posttransplantation.

PMID- 19765456
TI  - Effect of graft type on postoperative liver function recovery in living liver
      donors.
AB  - BACKGROUND: Donor safety is the primary focus in living-donor liver
      transplantation. Although, the procedure carries a significant risk of morbidity
      and even death, the use of marginal living donors is a current issue of
      discussion. PATIENTS AND METHODS: Between September 2001 and October 2008, we
      performed 203 liver transplantation procedures using organs from living donors.
      Of 203 donors, 115 were men and 88 were women, with a mean (SD; range) age of
      34.5 (9; 19-66) years. One hundred fifty donors were first-degree relatives of
      the recipients, 36 were second-degree relatives, and 17 were spouses. We did not
      accept grafts with remnant volume less than 40% or from donors with impaired
      liver function. We performed 96 right-lobe 38 left-lobe, and 69 left-lateral
      segmentectomies. For the right-lobe grafts, the median hepatic vein was always
      left in the remnant liver. The mean ratios of remnant to total donor liver volume
      were 42.0%, 66.8%, and 74.6% for the right-, left-, and left lateral
      segmentectomies, respectively. Mean hospitalization time was 7.0, 6.2, and 9.7
      days, respectively. Mean operative time was 330, 324, and 324 minutes,
      respectively. Only 15 donors (7.8%) received autologous blood transfusions during
      surgery. Liver function tests including alanine aminotransferase, aspartate
      aminotransferase and bilirubin concentrations and prothrombin time were assessed
      postoperative days 1, 3, and 5 at outpatient follow-up, usually at week 3.
      RESULTS: There were no deaths; however, 26 complications occurred in 20 of 203
      donors (5.2%), most of which were treated with radiologic interventions.
      CONCLUSION: Larger grafts produce impaired function in the early postoperative
      period; however, they do not have a negative effect in the long term. The remnant
      volume should be measured fastidiously, and surgeons must avoid taking large
      volumes of liver, especially in right-lobe donors.

PMID- 19765457
TI  - The prevalence and the impact of portopulmonary hypertension on postoperative
      course in patients undergoing liver transplantation.
AB  - INTRODUCTION: Portopulmonary hypertension (PPH) is an uncommon but serious
      complication of chronic liver disease. It is accepted to be a poor prognostic
      factor in the follow-up of patients who have undergone orthotopic liver
      transplantation (OLT). The presence of severe PPH is accepted as a
      contraindication to OLT. In this study we sought to identify the prevalence and
      impact of PPH on the outcome of OLT patients. PATIENTS AND METHODS: We
      retrospectively analyzed the records of 114 adult OLT patients operated on at our
      institution. A complete transthoracic Doppler echocardiographic examination was
      performed preoperatively and postoperatively. To identify PPH, patients with
      Doppler echocardiographically measured systolic pulmonary artery pressure (SPAP)
      values of >or=30 mm Hg were defined as PPH. We noted the etiology of the liver
      disease, the postoperative mortality rates, and the pulmonary complications among
      OLT patients with PPH. RESULTS: In 24 patients we detected PPH, a prevalence of
      21.1% among patients referred for OLT. Their mean age was 44.0 +/- 13.5 years; 18
      patients (75.0%) were males. With regard to the Child classification, 16 (66.7%)
      were in class C. The mean SPAP was 46.6 +/- 7.6 mm Hg. Compared with preoperative
      values, a significant decrease in mean SPAP was noted postoperatively; 46.6 +/-
      7.6 mm Hg vs 37.8 +/- 15.5 mm Hg (P < .05). Concerning postoperative pulmonary
      complications, pneumonia developed in 7 (29.2%), pleural effusion in 6 (25%), and
      respiratory failure and right ventricular failure in 1 (4.2%) subject. Compared
      with patients with a normal SPAP, the postoperative pulmonary complication rate
      was higher and the length of hospitalization longer among patients with PPH (P <
      .05). However, no difference was observed in terms of mortality rates (P > .05).
      CONCLUSION: This study indicated that SPAP decreased among patients with PPH
      following OLT. Although there was an increase in pulmonary complications, we
      observed no alteration in mortality rates. Therefore, we suggest that PPH may not
      be regarded as a contraindication for OLT.

PMID- 19765458
TI  - Pediatric liver transplantation in Iran: a 9-year experience.
AB  - BACKGROUND: Liver transplantation (OLT) is accepted as the standard therapy for
      end-stage liver disease. The current shortage of organ donors has led to the use
      of split grafts and living related donors to provide timely liver transplants for
      these children. Herein we have reported our experience with pediatric OLT over a
      9-year period. MATERIALS AND METHODS: We retrospectively studied 138 infants and
      children who underwent OLT from April 1999 to August 2008 including
      pretransplantation status, medical and surgical complications, and survival.
      RESULTS: There were 83 (60.1%) boys and 55 (39.9%) girls. The mean patient age
      was 9.1 +/- 5.6 years (range = 0.5-18) with a mean weight of 28.1 +/- 17.0 kg
      (range = 7-80). The main indications were Wilson's disease (20.3%); cryptogenic
      cirrhosis (16.7%); autoimmune cirrhosis (14.5%); biliary atresia (13.8%);
      tyrosinemia (9.4%); and progressive familial intrahepatic cholestasis (8.7%). We
      used living related donors in 54 (39.1%) and split livers in 20 (14.5%) cases
      with 64 (46.4%) patients receiving a whole liver from a deceased donor. The mean
      follow-up was 25.3 +/- 20.3 months (range = 1-100). The mortality rate was 27.5%
      with a 26.1% in-hospital mortality. The main causes of mortality were vascular
      complications (32.6%); primary nonfunction (19.6%); sepsis (17.4%); chronic
      rejection (17.4%); and biliary complications (6.5%). The mortality rate among
      patients under 10 kg (58.8%) was higher than that of patients over 10 kg (23.1%).
      Among those patients who were discharged from the hospital (73.9%), the most
      common cause of mortality was chronic rejection from noncompliance (n = 4),
      chronic rejection (n = 3 cases), or posttransplant lymphoproliferative disease (n
      = 2). CONCLUSION: Our results demonstrated that pediatric OLT is a feasible
      undertaking in Iran. The organ shortage in our area led to liberal use of living
      related and split-liver techniques. The overall results of pediatric OLT in Iran
      were acceptable.

PMID- 19765459
TI  - Experience of living donor liver transplantation in Iran: a single-center report.
AB  - BACKGROUND: Living donor liver transplantation (LDLT) has been accepted as a
      valuable treatment for patients with end-stage liver disease seeking to overcome
      the shortage of organs and the waiting list mortality. The aim of this study was
      to report our experience with LDLT. METHODS: We retrospectively analyzed 50 LDLTs
      performed in our organ transplant center from January 1997 to March 2008. We
      reviewed the demographic data, family history, operative and hospital stay
      durations as well as postoperation complications among donors and recipients. We
      also performed a retrospective analysis of recipient chemical and biochemical
      data. RESULTS: Among 50 patients (30 males and 20 females) of overall mean age of
      7.21 +/- 5.35 who underwent LDLT (10 right lobe, 38 left lobe, and 2 left lateral
      segments), 47 received a liver graft from their parent, two from a brother, and
      one from an uncle. The most common indications for LDLT were end-stage liver
      disease due to Wilson's disease (16%), cryptogenic cirrhosis (16%), tyrosinemia
      (14%), biliary atresia (12%), autoimmune hepatitis (12%), and progressive
      familial intrahepatic cholestasis (12%). The mean follow-up was 16.91 +/- 23.74
      months. There were 13 (26%) recipient mortalities including vascular
      complications; three to sepsis after bowel perforation, two from liver
      dysfunction, two from chronic rejection due to noncompliance, and one from
      diffuse aspergillosis. The morbidity rate was 50%, including 19 reexplorations
      during the hospital course and five biliary complications. CONCLUSION: This study
      demonstrated that LDLT can decrease the number of patients awaiting liver
      transplantation especially in the pediatric group. However, because of relatively
      high mortality and morbidity, we must improve our treatment outcomes.

PMID- 19765460
TI  - Split liver transplantation in Shiraz Transplant Center.
AB  - BACKGROUND: Cadaveric organ splitting emerged from an improved understanding of
      the surgical anatomy of the liver as a possible mechanism to expand the organ
      pool. In this study, we have reported our first series of split liver
      transplantations (SLT). MATERIALS AND METHODS: From June 2006 to June 2008, we
      performed 17 pairs of SLT: 70.6% ex situ and 29.4% in situ. The mean age of the
      donors (32 males, 2 females) was 23.15 +/- 9 years. All of them had been stable
      at the time of harvest according to vital signs, liver function tests,
      electrolytes, and urine output. The decision on splitting was made by the
      surgical team according to the donor's status and the urgency of the recipient.
      RESULTS: The main indications were biliary atresia (17.6%) followed by Wilson
      disease (14.7%) and cryptogenic cirrhosis (14.7%). The left lateral segment and
      the left lobe were used in 6 and 11 cases, respectively. In-hospital mortalities
      for the pediatric and adult groups were 68.4% and 26.7%, respectively. Primary
      graft nonfunction (52.9%), vascular complications (29.4%), sepsis (11.8%), and
      biliary complications (5.9%) were the main causes of mortality. CONCLUSION: Our
      experience indicated that SLT showed a high rate of mortality and morbidity.

PMID- 19765461
TI  - Living related liver transplantation in Crigler-Najjar syndrome type 1.
AB  - Four children underwent living related liver transplantation because of Crigler
      Najjar syndrome type 1. Three were infants aged 2, 8(1/2), and 15 months, and
      weighed 5, 8, and 10 kg, respectively. Pretransplantation unconjugated bilirubin
      concentration was 22 to 30 mg/dL despite 12 to 14 hours of phototherapy daily.
      Patient 1, the 2-month-old infant, with unconjugated bilirubin concentration of
      30 mg/dL, had a high-pitched cry, suggestive of bilirubin encephalopathy; results
      of neurologic examination were normal. Plasmapheresis and urgent liver
      transplantation were performed. Patient 4, a 13-year-old girl, had learning
      difficulties at school and attended a special class. Three patients received left
      lateral liver segments, and 1 patient received a left lobe. Biliary
      reconstruction was completed with duct-to-duct anastomosis. Bile leakage
      developed at the anastomosis in 2 patients, which was treated successfully with
      cholangioplasty. In all patients, the unconjugated bilirubin concentration
      normalized by day 1 posttransplantation, and no phototherapy was necessary. After
      transplantation, the 2-month-old infant with suspected encephalopathy exhibited
      hypotonia, spasticity of the lower extremities, and lack of head control. He died
      after vomitus aspiration during sleep at 10 months posttransplantation. The other
      3 patients are alive with normal neurodevelopmental milestones. Irreversible
      brain damage may occur early in the course of Crigler-Najjar syndrome type 1.
      Urgent treatment including plasmapheresis, exchange transfusion, phototherapy,
      and liver transplantation may not reverse brain damage. Young infants must be
      evaluated carefully for subtle signs and symptoms of bilirubin encephalopathy.
      Liver transplantation is curative if performed before development of neurologic
      dysfunction.

PMID- 19765462
TI  - The role of valacyclovir on Epstein-Barr virus viral loads in pediatric liver
      transplantation patients.
AB  - INTRODUCTION: Epstein-Barr virus (EBV) infection occurring in the postoperative
      period represents a significant risk for pediatric transplant recipients. It
      presents in various manners, including a mononucleosis-like syndrome, hepatitis,
      encephalopathy, or posttransplant lymphoproliferative disease (PTLD).
      Valacyclovir has in vitro activity against EBV. We sought to review our
      experience with valacyclovir on peripheral blood EBV viral loads among a group of
      EBV-infected patients after liver transplantation (OLT). PATIENTS AND METHODS:
      Twelve children of ages 6-36 months (median, 12 months), underwent OLT. Eight
      (66%) were EBV immunoglobulin (Ig)G seronegative at the time of the operation.
      Eight patients developed primary infection and 4 patients developed reactivation
      of a post primary infection. Valacyclovir was prescribed immediately to 3
      patients when we detected an acute-primary EBV infection. Valacyclovir was
      prescribed for 2 patients who had primary EBV infections followed by PTLD. Three
      patients who had primary EBV infection were administered valacyclovir after they
      became chronically EBV PCR positive for more than 1 year. Four out of 12 cases
      (33%) were EBV seropositive at the time of OLT, and underwent postprimary EBV
      reactivation displaying chronic EBV carrier state for 8-10 months before
      valacyclovir treatment. Peripheral blood EBV viral loads were tested every 2
      months. The primary outcome was the proportion of subjects with EBV viremia who
      had a >or=2 log 10 decrease in EBV copies/mL after valacyclovir treatment. The
      duration of valacyclovir treatment was a median of 10 months (range, 8-11
      months). At the beginning of the treatment period the median level of EBV viral
      load was 1.1 x 10(4) (range, 1 x 10(4) to 1 x 10(7)). EBV virus was cleared in
      only 1 patient with primary acute EBV infection. EBV viral loads did not change
      in 7 of 12 patients and decreased only 1 log 10 (n = 2) or 2 log 10 (n = 2).
      CONCLUSION: In this small, non-placebo-controlled study, valacyclovir treatment
      was not effective to decrease peripheral blood EBV viral loads.

PMID- 19765463
TI  - Posttransplant lymphoproliferative disease in pediatric liver transplant
      recipients.
AB  - Posttransplant lymphoproliferative disease was first reported in 1968.
      Posttransplant lymphoproliferative disease encompasses a range of abnormalities
      from benign infectious mononucleosis-like illnesses to non-Hodgkin's lymphomas
      with nodal and extranodal site involvement. We evaluated five children who had
      posttransplant lymphoproliferative disease after liver transplantation. Since
      2001, we have performed 118 liver transplantations in 115 children. Five children
      (4.6%), including three girls and two boys of overall mean age, 3.9 year,
      developed posttransplant lymphoproliferative diseases. The indications for liver
      transplant were hepatoblastoma in one recipient and cholestatic liver disease in
      the remaining four subjects. Posttransplant lymphoproliferative disease was
      diagnosed at 6, 11, 17, 22, and 27 months after the liver transplantation.
      Imaging modalities identified generalized lymphadenopathy in one, multiple liver
      masses in one, a large portal mass in one, multiple stomach ulcers in one, and a
      large mediastinal mass in one recipient. At diagnosis, the recipient with the
      large mediastinal mass displayed cough; the remaining four recipients were
      asymptomatic. Histological findings showed B-cell lymphomas in three recipients
      and T-cell lymphomas in two. The results of in situ hybridization for Epstein
      Barr virus were negative in one recipient and positive in four. Four recipients
      were treated with chemotherapy; the remaining recipient was treated with anti
      CD20 monoclonal antibodies. The one recipient who had a large mediastinal mass
      died at 2 months after receiving the diagnosis of chemotherapy-related sepsis;
      the remaining four children are alive at 9, 11, 18, and 34 months after
      treatment. Our rate of posttransplant lymphoproliferative disease was similar to
      that in the literature. From a few months to several years after liver
      transplantation, radiologists must be alert to the possibility of posttransplant
      lymphoproliferative disease. Thorough imaging is required to detect the wide
      variety of potential presentations.

PMID- 19765464
TI  - Eight years of lung transplantation: experience of the National Research
      Institute of Tuberculosis and Lung Diseases.
AB  - BACKGROUND: Lung transplantation has evolved from an experimental procedure to a
      viable therapeutic option in many countries. In Iran, the first single-lung
      transplantation was performed in the year 2000, more than 3 decades after the
      first successful procedure in the world, and the first double-lung
      transplantation was performed in the year 2006. OBJECTIVE: To describe our 8-year
      experience in lung transplantation. PATIENTS AND METHODS: During 8 years, we
      performed 24 lung transplantation procedures. Underlying lung diseases were
      pulmonary fibrosis in 16 patients (66.6%); chronic obstructive pulmonary disease
      in 2 (8.3%); bronchiectasis in 5, including 2 patients with cystic fibrosis
      (20.8%), and alveolar microlithiasis in 1 (4.16%). Data for all patients were
      collected and analyzed. Procedures were carried out using standardized methods.
      The induction suppression regimen consisted of cyclosporine and
      methylprednisolone. Maintenance immunosuppression drugs were cyclosporine and
      mycophenolate mofetil, and tapering dosage of prednisolone. Patients were
      followed up with physical examinations, 3 times a week, as well as and cycle
      ergometry 3 times a week and spirometry and laboratory tests once a week and
      chest radiography per needed for up to 3 months posttransplantation. RESULTS: The
      longest survival time was 7.2 years, in a 60-year-old patient with idiopathic
      pulmonary fibrosis. Fourteen patients died, 8 as a result of hemodynamic
      instability and/or hemorrhage, 1 as a result of bone and fat emboli, 3 after
      cessation of drug and 2 of them after infection. CONCLUSION: Although lung
      transplantation is a complex procedure it can be performed in developing
      countries such as Iran.

PMID- 19765465
TI  - Apoptosis and proliferation of cardiomyocytes and interstitial mononuclear cells:
      association with rejection and macrophage infiltration.
AB  - Previous studies have noted that acute rejection episodes (AREs) may lead to loss
      of cardiomyocytes in transplanted hearts. The aim of this study was twofold;
      first, to assess the degree of apoptotic cells and to compute the proliferation
      index of cardiomyocytes and mononuclear interstitial infiltrates in cardiac
      allografts. Second, we sought to determine whether apoptosis involved in AREs was
      associated with macrophage infiltration. Among 28 endomyocardial biopsies, 18
      showed AREs and the remaining 10 biopsies, nonspecific changes, the control
      group. All biopsies were immunostained with Ki-67 and CD68 antibodies. Apoptotic
      cells were counted using the terminal deoxyncleotidyl transferase dUTP nick end
      labeling method. Apoptotic death of cardiac myocytes and interstitial mononuclear
      cells was significantly greater in cases of allograft rejection compared with the
      control group (P < .05). In addition, compared to the control group, ARE cases
      showed a greater proliferation index of cardiac myocytes and interstitial cells
      (P < .05). Macrophage infiltration was significantly greater in ARE cases and
      macrophage infiltration showed a linear association with both apoptosis and
      proliferation of myocytes and interstitial cells (P < .001). In conclusion, we
      verified the presence of apoptotic cell death during acute rejection in heart
      transplants. Apoptotic cell death was significant among interstitial cells but it
      was less among cardiac myocytes. Macrophage infiltration had a great influence on
      apoptotic cell death of myocytes and interstitial cells.

PMID- 19765466
TI  - Chronic kidney disease after hematopoietic cell transplantation: frequency, risk
      factors, and outcomes.
AB  - BACKGROUND: Occurrence of chronic kidney disease (CKD) after hematopoietic cell
      transplantation (HCT) is rare with relatively few reported cases. The aim of this
      study was to evaluate the frequency of CKD among patients who received HCT for
      hematologic and nonhematologic disorders. OBJECTIVE: We performed a prospective
      study to evaluate the frequency of CKD and its risk factors. Between 1997 and
      2006 there were 1693 patients engrafted at the Bone Marrow Transplant Research
      Center. METHOD: CKD was defined as a doubling of serum creatinine level from the
      baseline and after 1 year from receiving a transplantation. The risk of CKD in
      relation to a non-based total body irradiation conditioning regimen, the type of
      graft (allograft autograft), and the incidences of graft-versus-host disease
      (GVHD), drug toxicity, and veno occlusive disease (VOD) were examined in 1963 HCT
      patients. RESULTS: Kidney involvement developed in 66 patients (4%). By 6-12
      months after HCT, approximately 33% of these patients developed CKD (23 patients:
      19 allograft and 4 autograft). In most CKD patients, the cause was idiopathic. In
      23 patients who developed CKD, 5 patients had acute kidney injury during the
      transplantation period with GVHD. Other renal involvements were as follows:
      hypertension (17%), proteinuria (15%), hydronephrosis (2%), hematuria (18%), and
      diabetes (3%). CONCLUSION: The frequency of CKD in this study seems to be high.
      It is important to know the specific type of kidney damage, to determine when to
      be aware of the time of occurrence of renal complications and to understand the
      best methods to treat patients with renal injury secondary to nephrotic syndrome
      and idiopathic CKD.

PMID- 19765467
TI  - Impact of human cytomegalovirus infection UL55-nested polymerase chain reaction
      method in hematopoietic stem cell transplant donors and recipients.
AB  - Human cytomegalovirus (HCMV) is one of the most important and critical viral
      causes of graft rejection among hematopoietic stem cell transplant (HSCT)
      recipients. Monitoring of this viral infection has a critical role in the
      management of HSCT clinical complications. In this retrospective cohort, blood
      (plasma and buffy coat) and urine samples were collected from 110 HSCT patients
      and 95 donors pretransplantation and weekly for 100 days posttransplantation. An
      HCMV-optimized UL55-nested polymerase chain reaction (PCR) method was used to
      detect HCMV infection. Genotyping of the HCMV UL55 gene was performed for all
      UL55-nested, PCR-positive samples. HSCT donor and recipient laboratory and
      clinical data were statistically analyzed using SPSS version 15 software. UL55
      nested, PCR-positive results were obtained in 3540/4950 (71.5%), 3634/4950
      (73.4%), and 3292/4950 (66.5%) of these plasma, buffy coat, and urine samples,
      respectively. Twenty-five percent of transplant donors were infected with HCMV.
      An increase in HCMV infection was observed from pre- to post-HSCT conditions.
      Detection of the gB2 UL55 genotype in most transplant patient samples suggested
      the need to examine the possible impact of HCMV UL55 genotypes and HCMV
      infections among stem cell transplant recipients.

PMID- 19765468
TI  - The role of different risk factors in clinical presentation of hemorrhagic
      cystitis in hematopoietic stem cell transplant recipients.
AB  - Various risk factors play roles in hemorrhagic cystitis (HC) presentation and
      grading in hematopoietic stem cell transplant (HSCT) patients. We retrospectively
      sought to study these risk factors among the clinical and laboratory records of
      283 patients transplanted between 1995 and 2007. Most patients underwent a
      myeloablative conditioning regimen, but some, a nonmyeloablative regimen. The
      collected results were analyzed using version 16 of SPSS soft ware. HC was
      observed in 120 patients (42.4%). The most cases of early onset of HC were
      detected among donor-recipient gender mismatches (P = .086). Significant
      correlations were detected between late onset of HC with use of bone marrow as a
      source of stem cells (P = .001), as well as with class II or III of thalassemia
      as an underlying disease in HSCT recipients (P = .019). Treatment with
      cyclophosphamide with busulfan or with antithymocyte globulin (ATG) as the
      transplant conditioning regimen increased the risk of late-onset HC (P = .001 or
      P = .073, respectively). A significant relationship was diagnosed between lower
      grades and late onset of HC with anti-human cytomegalovirus gancyclovir or
      intravenous immunoglobulin (IVIg) therapy (P = .002). The results of this study
      showed that significant correlations to the incidence and severity of HC clinical
      symptoms in HSCT patients among allogeneic transplantations, donor-recipient
      gender mismatches, bone marrow as a stem cell source, class II and III of
      thalassemia, use of busulfan plus cyclophosphamide plus ATG in the conditioning
      regimen, graft-versus-host disease (GVHD) symptoms, use of prednisolone and
      cyclosporine as prophylaxis treatment of GVHD, and gancyclovir and IVIg as
      antiviral drugs.

PMID- 19765469
TI  - Effect of bicarbonate administration on cyclosporine-induced nephrotoxicity in
      rats.
AB  - BACKGROUND: Cyclosporine (CsA) is known to cause metabolic and distal tubular
      acidosis. There is some evidence that CsA reduces net HCO(3)(-) absorption. The
      aim of this study was to elucidate whether bicarbonate administration prevented
      CsA-induced functional or structural nephrotoxicity. METHODS: Seven days after
      uninephrectomy, 20 rats were divided into 4 groups. NaHCO(3) (0.28 mol/L) was
      added in drinking water for 7 days, whereas control rats received regular tap
      water. The bicarbonate pretreated rats were administered either CsA (50 mg/kg
      intraperitoneally) or vehicle daily for a week. At the end of the procedure,
      animals were placed in metabolic cages for 24 hours after which we measured
      creatinine clearance (Ccr), urinary total proteins, pH, and N-acetyl-beta-D
      glucosaminidase (NAG) activity. The kidney was fixed in formaldehyde. RESULTS:
      Ccr was significantly affected by the administration of CsA. The effects of CsA
      on serum pH and HCO(3)(-) concentration were prevented by pretreatment with
      NaHCO(3). However, it did not affect the CsA-induced increased urinary NAG
      activity or decreased Ccr. There was no protection of CsA-induced changes in
      renal tissues by NaHCO(3). CONCLUSION: Overall NaHCO(3) administration did not
      prevent CsA-induced changes in Ccr and NAG activity. These data suggested
      involvement of factors other than acid-base status in CsA-induced nephrotoxicity.
      However, correction of acidosis should still be considered for patients receiving
      CsA because acidosis exacerbates tissue damage.

PMID- 19765470
TI  - Proteinuria is reduced by inhibition of inducible nitric oxide synthase in rat
      renal ischemia-reperfusion injury.
AB  - BACKGROUND: Ischemia-reperfusion (IR)-induced nephrotoxicity is associated with
      proteinuria. There are reports on the involvement of inducible nitric oxide
      synthase (iNOS) in proteinuria in conjunction with renal disease. This study was
      designed to investigate the effect of N6-(1-iminoethyl)-L-lysine hydrochloride (L
      Nil), a selective inhibitor of iNOS, to prevent proteinuria in IR injury.
      METHODS: Ischemia was induced by 40-minute clamping of the renal arteries
      followed by 6-hour reperfusion. Rats were administered either L-Nil (3 mg/kg
      intravenous bolus followed by infusion of 1 mg/kg/h) or saline. To monitor
      glomerular and tubular functional changes before and after treatment, we measured
      blood urea nitrogen, plasma creatinine, and urinary N-acetyl-beta-D
      glucosaminidase activity. Total protein (TP), albumin, and low- (LMW) and high
      molecular-weight (HMW) protein excretion rates were determined by sodium dodecyl
      sulfate polyacrylamide gel electrophoresis of urine samples. Kidney
      ultrastructure was examined through a transmission electron microscope (TEM).
      RESULTS: IR resulted in significant LMW and HMW proteinuria. L-Nil significantly
      prevented the IR-induced increases in TP, albumin, and alpha1-microglobulin
      excretion. TEM showed loss of microvilli of the proximal tubule cells, injured
      mitochondria, and foamy changes in the structure of nuclear and cytoplasm in IR
      group. L-Nil reduced IR-mediated renal ultrastructural changes and tubular
      proteinuria. DISCUSSION: This study suggested possible differences in the
      mechanism(s) of nephrotoxicity induced by iNOS in the glomeruli and tubular
      cells. The types of proteins excreted in the urine should be considered in the
      treatment strategy. In conclusion, this study suggested the involvement of iNOS
      in IR-induced tubular proteinuria.

PMID- 19765471
TI  - Changes in serum and renal vitamin E levels in deoxycorticosterone acetate-salt
      hypertensive rats.
AB  - BACKGROUND: Hypertension is an important risk factor for the progression of
      chronic renal disease, which may result in the development of end-stage renal
      disease. Since reactive oxygen species are implicated in the induction of
      hypertension, antioxidants have been used to reduce blood pressure and renal
      impairment in animal models and in human hypertension. However, the available
      data are not conclusive. METHODS: To investigate oxidative stress in
      hypertension, we evaluated renal and serum vitamin E levels as the most effective
      antioxidant to reduce lipid peroxidation by high-performance liquid
      chromatography among rats subjected to deoxycorticosterone acetate (DOCA)-salt
      treatment for 4 weeks. Renal levels of malondialdehyde (MDA) as a marker of cell
      lipid peroxidation were also assayed in treated rats. Systolic blood pressure
      (SBP) was measured in conscious rats by the tail-cuff method using a PowerLab/4sp
      data acquisition system. RESULTS: SBP increased significantly in DOCA-salt
      treated rats compared to the sham group after 4 weeks of treatment. Serum vitamin
      E levels were significantly lower and renal MDA concentrations significantly
      higher in treated compared to sham rats. However, renal vitamin E levels were
      also significantly higher among treated compared to sham rats. DISCUSSION:
      Decreased plasma vitamin E levels and increased renal MDA levels show systemic
      and local oxidative stress in DOCA-salt-treated rats. However, the higher renal
      vitamin E level suggested a local compensatory mechanism. Vitamin E
      administration might be appropriate, as significant decreases in vitamin E levels
      were observed in the serum of DOCA-salt-treated rats.

PMID- 19765472
TI  - Cytomegalovirus-induced adrenal insufficiency in a renal transplant recipient.
AB  - Cytomegalovirus (CMV) is an important pathogen in organ-transplant recipients.
      There have been frequent reports of CMV-induced adrenal insufficiency in patients
      with human immunodeficiency virus infection. Herein, we report CMV-induced renal
      insufficiency in a renal transplant recipient. A 24-year-old woman had gradual
      onset of weakness, anorexia, nausea, hypotension, and skin hyperpigmentation at 5
      months after renal transplantation. The immunosuppression regimen included
      cyclosporine, mycophenolate mofetil, and corticosteroid (prednisolone, 5 mg/d).
      Recent history included acute CMV infection, which was treated with ganciclovir.
      Basal serum cortisol concentration was 4 microg/dL, and stimulated serum cortisol
      concentration was less than 10 microg/dL. All clinical signs and symptoms and
      hypotension gradually improved after the oral prednisolone dose was increased to
      10 mg/d. Clinicians must be aware of the possibility of CMV-induced adrenal
      insufficiency in renal transplant recipients. The condition may be symptomatic
      despite low-dose prednisolone therapy.

PMID- 19765473
TI  - Hyalohyphomycosis caused by Paecilomyces lilacinus after kidney transplantation.
AB  - Hyalohyphomycosis caused by Paecilomyces has rarely been described among solid
      organ recipients. Its management is elusive without an established consensus
      concerning antifungal therapy. Herein we have reported a case of extensive
      cellulitis caused by Paecilomyces lilacinus observed in a 48-year-old kidney
      transplanted woman with hepatitis C. Kidney transplantation from a cadaveric
      donor was performed in October 2006 with an uneventful early course except for
      posttransplant diabetes mellitus and a reversible acute rejection episode.
      Cutaneous nodular and verrucous lesions of the left leg appeared in August 2007.
      In a few weeks, these lesions become ulcerated, hemorrhagic, and painful. The
      diagnosis was made on the basis of microbiologic culture and histological
      examination. There was no improvement in the skin lesions after 6 weeks treatment
      with itraconazole, but voriconazole yielded a good response within the first 2
      weeks. There was a good tolerance to antifungal therapy; graft function and liver
      tests remained normal. We concluded that an increasing emerging of fungal
      infections is observed with the introduction of more powerful immunosuppressive
      drugs. Diagnosis and management of such infections is elusive. Preventive
      measures should be considered including the adaptation of immunosuppressive
      therapy among at-risk patients especially those with hepatitis C virus infection
      and diabetics.

PMID- 19765474
TI  - Brown tumor of hyperparathyroidism masquerading as central giant cell granuloma
      in a renal transplant recipient: a case report.
AB  - The brown tumor of hyperparathyroidism is histologically identical to the central
      giant cell granuloma (CGCG), but these lesions can be differentiated based on
      history and laboratory findings. Herein we have reported a 46-year-old renal
      transplant recipient in whom brown tumors of hyperparathyroidism were detected
      several years following renal transplantation. The lesions initially masqueraded
      as a CGCG with an intranasal mass and ethmoid bone involvement at 7-years
      posttransplantation, for which surgical resection had been performed. Six years
      later, she developed multiple expansile bony lesions of the chest wall with
      histologic features of multinucleated giant cells. A markedly elevated
      parathyroid hormone level led us to make a diagnosis of brown tumor of
      hyperparathyroidism. Hence, we propose that clinicians consider brown tumor of
      hyperparathyroidism to be a potential cause of giant cell lesions among renal
      transplant recipients. Moreover, careful follow-up examinations are required for
      such patients to make a timely and accurate diagnosis.

PMID- 19765475
TI  - Renal transplantation and idiopathic thrombocytopenic purpura: two case reports.
AB  - Kidney transplantation has rarely been performed in patients with immune
      thrombocytopenic purpura (ITP). We present two cases of kidney recipients from
      unrelated donors in women who had prior chronic refractory ITP. Their
      immunosuppression included induction therapy with antithymocyte globulin (ATG)
      and maintenance treatment with cyclosporine and prednisone. Kidney
      transplantations were safely performed without any complication. The platelet
      count of our patients increased gradually after the surgery, and maintenance with
      cyclosporine, mycophenolate mofetil, and prednisolone allowed graft function and
      satisfactory hemostasis. During the 3- and 8-year follow-up periods in our
      recipients, graft function was well maintained. We speculated that
      immunosuppressive agents, especially cyclosporine, may result in safe platelet
      counts and resolve thrombocytopenia in cases with refractory ITP prior to
      transplantation.

PMID- 19765476
TI  - Fat and bone marrow embolization in a donor as the cause of death in a lung
      recipient.
AB  - The cause of death in organ donors may have a great impact on organ recipient
      outcomes. Trauma is the prevailing cause of death among brain-dead patients in
      Iran and many other countries. Such patients may have many complications, among
      them vascular embolization with fat and other tissues. We have described herein a
      case of vascular embolization in a donor and its consequence on the recipient's
      outcome. The recipient was a 36-year-old woman with pulmonary fibrosis, who
      received a single lung transplant from a patient brain dead due to trauma. Donor
      had no obvious fractures; the oxygen challenge test was ideal. The harvested lung
      was normal upon bronchoscopy and it was clear on plain chest radiography. The day
      after lung transplantation, the recipient was extubated successfully with normal
      O(2) saturation. On computed tomography scan, there was a fixed infiltration at
      the base of the transplanted lung. On day 5 posttransplantation, the infiltrate
      expanded and the patient developed acute respiratory distress syndrome (ARDS).
      The patient's condition deteriorated rapidly and she expired on day 10
      posttransplantation due to ARDS. The pathologic examination of the brain-dead
      patient, which was obtained from another patient's lung, was available after our
      recipient's death, showed massive vascular fat and bone marrow embolization. In
      the mentioned case, all criteria for lung harvest from the brain-dead patient
      were met. Looking for embolization is not among the criteria for lung
      transplantation if chest radiography is clear and O(2) challenge test is
      acceptable, but we observed a poor recipient outcome due to bone and fat
      embolization in the donor's lung. When transplanting from a traumatic patients,
      such complications should be kept in mind.

PMID- 19765477
TI  - Extensive sino-orbital zygomycosis after heart transplantation: a case report.
AB  - BACKGROUND: Zygomycosis is an opportunistic fungal infection mainly affecting
      patients with diabetes mellitus, immunodeficiency, and malignancies. The majority
      of cases in which it has been reported as a posttransplantation complication have
      been after renal or liver transplantation. There are few instances of rhino
      sinusitis and orbital mucormycosis complicating heart transplantation. CASE
      REPORT: A 38-year-old diabetic man who had undergone heart transplantation
      returned to the transplantation follow-up clinic 20 days after a successful
      operation with unilateral periorbital swelling, nasal discharge, and multiple
      cranial nerve dysfunctions. Multidisciplinary investigations resulted in
      detection of mucormycosis in the paranasal sinuses and the orbital space, as well
      as a thrombosis of the cavernous sinus. Surgical ablation of the infected parts,
      along with antifungal treatment and adjustment of immunosuppressive maintenance,
      restricted extension of the craniofacial involvement. Allograft function remained
      undisturbed. CONCLUSION: Early detection of opportunistic infections in
      transplant recipients plays a big role in preventing dissemination. Fungal
      infections, including zygomycosis, should be considered for recipients,
      especially those with risk factors, such as diabetes, who present with local
      unusual manifestations. Sinonasal and orbital mucormycosis, if diagnosed in
      timely fashion, can be managed to reduce mortality. Although devastation of one
      side facial and ophthalmic structures was inevitable in this case, the overall
      outcome was acceptable.

PMID- 19765478
TI  - Non-marginal donor C-loop ulcers as a cause of gastrointestinal bleeding after
      pancreas transplantation: three case reports.
AB  - Unfortunately, pancreas transplantation (PTx) has been associated with the
      highest surgical complication rate of all the routinely performed organ
      transplant procedures. Complications can arise not only from the pancreas itself
      but also from the simultaneously transplanted duodenum. One of these
      complications is gastrointestinal bleeding, which might be from anastamotic site
      ulcer, pseudoaneurysm, arterioenteric fistula, severe rejection, or
      cytomegalovirus infection. In this case series, we present three patients
      presented with severe anemia 3 to 6 months after PTx with enteric drainage by end
      to-end anastomosis of ascending loop of a Roux-en-Y to donor duodenal C-loop. The
      source of bleeding in all three cases was non-marginal donor duodenal C-loop
      ulcers. High donor pancreas exocrine output associated with relatively low
      drainage of a small end-to-end anastomosis may be the cause of these ulcers. It
      is recommended to use a side-to side anastomosis to prevent this complication.

PMID- 19765479
TI  - Endogenous Aspergillus endophthalmitis occurring after liver transplantation: a
      case report.
AB  - Endogenous Aspergillus endophthalmitis (AE) is a rare complication of invasive
      aspergillosis in transplant patients. In this report, we have described a patient
      who underwent liver transplantation because of drug-induced cholestatic cirrhosis
      and developed AE at 2 weeks after the surgery. The patient was a 22-year-old man
      who received a right liver lobe from his father. The operation was uneventful but
      the patient developed signs and symptoms of small-for-size syndrome after the
      second day of surgery. The patient received intense immunosuppression with
      methylprednisolone for 3 days, tacrolimus and mycophenolate mofetil from the
      first day after the operation, with ceftriaxone and metronidazole as prophylactic
      antibiotics. Because of signs of respiratory distress with pneumonia, vancomycin
      and amphotericin B were added empirically to his regimen. Polymerase chain
      reaction for aspergillus DNA in the blood was positive. The patient received one
      course of methylprednisolone pulse therapy for signs of acute rejection at day
      10, and tacrolimus was changed to sirolimus because of a rising serum creatinine
      and convulsions. After 2 weeks, the patient's symptoms improved and liver
      function tests were normal, but the complained of sudden intense pain in the left
      eye with unilateral blurred vision, redness, and other signs of endophthalmitis
      upon examination by an ophthalmologists. After 24 hours, visual acuity decreased
      to light perception. AE was confirmed by microscopy and culture of the vitreous
      fluid and retinal biopsy. Despite changing amphotericin to intravitreal injection
      of voriconazole followed by intravenous voriconazole and transient resolution of
      the symptoms, no improvement was seen in visual acuity. Pain and signs of
      inflammation in the eye recurred after 2 weeks. At last the patient underwent
      enucleation for resistant infection and fear of involvement of the other eye by
      aspergillosis or sympathetic ophthalmia.

PMID- 19765480
TI  - Liver transplantation in management of alveolar echinococcosis: two case reports.
AB  - Hepatic alveolar echinococcosis is an infectious disease caused by the larval
      stage of Echinococcus multilocularis, which grows primarily in the liver of an
      infected person and develops as a tumorlike lesion. In advanced cases, the
      organisms infiltrate every organ neighboring the liver and spread hematogenously
      to distant organs such as lungs and brain. Surgical resection and liver
      transplantation are accepted treatment options for early and advanced disease,
      respectively. Herein, we present case reports of 2 patients with advanced
      alveolar echinococcal disease that invaded both lobes of the liver and
      neighboring vital structures including the inferior vena cava. Despite the
      technical difficulty of the surgery, both patients were successfully treated with
      living donor liver transplantation. Liver transplantation should be accepted as a
      life-saving treatment of choice in patients with alveolar echinococcosis for whom
      there is no other medical or surgical treatment options.

PMID- 19765481
TI  - Liver transplantation for homozygous familial hypercholesterolemia: two case
      reports.
AB  - Homozygous familial hypercholesterolemia (HFHC) is a rare inherited condition
      with an incidence of one in one million. It is associated with severe premature
      atherosclerosis and early death from cardiovascular complications. Mutation in
      the gene that encodes the synthesis of the cellular receptor for low-density
      lipoprotein (LDL) is responsible for this metabolic disorder. Currently, the only
      effective treatment for this disease is liver transplantation, which alone or in
      association with medications, normalizes plasma cholesterol level. The authors
      report the results of liver transplantation for two cases of HFHC. The first
      case, a 15-year-old boy received a whole liver from a deceased donor, and the
      second, an 11-year-old boy, received a left liver lobe transplant from his
      mother's sister. Their preoperative fasting lipid concentrations were grossly
      raised. The older boy had severe atherosclerotic heart disease and had undergone
      coronary artery bypass grafting 5 months before transplantation. Both had
      preoperative plasma cholesterol levels higher than 750 mg/dL with normal thyroid
      and liver function tests. After the operation, the patients received
      methylprednisolone as pulse therapy followed by oral prednisolone, mycophenolate
      mofetil, and tacrolimus for immunosuppression. Their hospital stays were 24 and
      13 days, respectively. The first case needed reexploration because of bleeding on
      the second day after the operation. The lipid concentrations rapidly returned to
      the normal range in the first week after the operation, remaining in this range
      over the first 6 months of follow-up. Liver transplantation offers an highly
      effective treatment for HFHC. It is better to operate on patients before severe
      atherosclerotic changes in the coronary arteries. All patients must undergo a
      complete cardiac evaluation before surgery.

PMID- 19765482
TI  - Renal disease. Preface.

PMID- 19765483
TI  - Geriatric nephrology: old or new subspecialty.
AB  - In the 1980s geriatric nephrology was introduced as a subspecialty in
      anticipation of the increased number of elderly and very elderly people during
      the 21st century. There has been more clinical research dedicated to geriatric
      nephrology, education on the subspecialty has been implemented at national and
      university level, and funds for career development have been instituted over the
      past two decades. Our treatment of the elderly and very elderly patients seems to
      be more focused on their biologic age rather than chronologic age; they undergo
      diagnostic tests such as kidney biopsies and are candidates for kidney
      transplant. Although great strides have been made in the assimilation of
      geriatrics into nephrology more has to be done. This article examines the areas
      of research that encompass geriatric nephrology and clinic observations
      applicable to the care of the geriatric population.

PMID- 19765484
TI  - Anatomic and physiologic changes of the aging kidney.
AB  - Aging is a degenerative biologic process that affects the kidneys. It is known to
      be associated with a decline in kidney function coincident with a progressive
      decrease in the number of functioning nephrons and with glomerular and
      tubulointerstitial scarring. These changes affect glomerular and tubular
      function, systemic hemodynamics, and, as a whole, body homeostasis.

PMID- 19765486
TI  - Clinical presentation of renal failure in the aged: chronic renal failure.
AB  - Chronic kidney disease is increasingly being recognized in elderly individuals
      across the world. An understanding of the methods used to estimate or to measure
      kidney function, the likelihood and factors associated with progressive decline
      in renal function, and the clinical syndromes associated with poor renal function
      are key topics for individuals working across many medical disciplines. This
      review addresses some of the important aspects of chronic kidney disease, and
      summarizes some of the clinical and laboratory features associated with
      progressive disease.

PMID- 19765487
TI  - Diabetic nephropathy in the elderly.
AB  - Although diabetes is clearly linked to macro- and microvasculopathy in multiple
      organs resulting in cardiovascular and cerebrovascular catastrophic diseases,
      blindness, and limb amputations, it is the relentless progression of diabetic
      nephropathy toward becoming the major cause of end-stage renal disease (ESRD)
      that now challenges budgets and treatment facilities providing hemodialysis,
      peritoneal dialysis, and kidney transplantation. Nephrology, as a specialty, is
      now dominated by the necessity to address geriatrics and endocrinology to cope
      with the tidal wave of elderly ESRD patients suffering from uremia caused by
      diabetes. On the brighter side, emergence of effective renoprotective regimens
      now slow the incidence rate of ESRD in those with diagnosed diabetes. There is
      bona fide reason to hope that within a decade, kidney failure attributable to
      diabetes will be transformed into a preventable complication of a disease that
      has dominated and directed our heritage.

PMID- 19765485
TI  - Acute kidney injury in the elderly.
AB  - The aging kidney undergoes several important anatomic and physiologic changes
      that increase the risk of acute kidney injury (formerly acute renal failure) in
      the elderly. This article reviews these changes and discusses the diagnoses
      frequently encountered in the elderly patient with acute kidney injury. The
      incidence, staging, evaluation, management, and prognosis of acute kidney injury
      are also examined with special focus given to older adults.

PMID- 19765488
TI  - Hypertension in the elderly.
AB  - Hypertension is an important risk factor for cardiovascular morbidity and
      mortality, particularly in the elderly. Blood pressure elevation in the elderly
      is due to structural and functional changes that occur with aging. Treatment of
      hypertension reduces the risk of stroke, heart failure, myocardial infarction,
      all-cause mortality, cognitive impairment, and dementia in elderly patients with
      hypertension. A healthy lifestyle helps hypertension management, with benefits
      extending beyond lowering of blood pressure. Several classes of antihypertensive
      drugs are effective in preventing cardiovascular events. Treatment decisions
      should be guided by the presence of compelling indications such as diabetes or
      heart failure and by the tolerability of individual drugs or drug combinations in
      individual patients. The concomitant intake of certain medications that counter
      the effects of antihypertensive drugs and the frequent occurrence of orthostatic
      hypotension complicate treatment in older patients and drive down blood pressure
      control rates.

PMID- 19765489
TI  - Glomerular disease in the elderly.
AB  - Chronic glomerular disease is a common cause of disability and mortality in the
      elderly. The underlying cause of the glomerular disease in this population is
      diverse but can generally be divided into those that affect the kidneys primarily
      (primary glomerular disease) and those in which the kidney damage is a part of a
      systemwide process (secondary glomerular disease). This article briefly outlines
      the common presentations of glomerular disease in the elderly and discusses the
      clinical features, prognosis, and management of the primary and secondary
      glomerular diseases in this population of patients.

PMID- 19765490
TI  - Urinary tract infections in the elderly.
AB  - Urinary infection is the most common infection in elderly populations. There is a
      high prevalence of asymptomatic bacteriuria, but this is benign and does not
      require treatment. A urine specimen for culture should be obtained before
      initiating antimicrobial therapy for symptomatic infection. Antimicrobial
      treatment regimens in the elderly are similar to other populations. Chronic
      indwelling catheters are associated with increased morbidity from urinary tract
      infection.

PMID- 19765491
TI  - Obstructive uropathy.
AB  - Obstructive uropathy is a relatively common condition in which an anatomic or
      functional problem causes obstruction to normal urinary flow. Obstructive
      uropathy becomes more prevalent with increasing age and is most frequent as a
      result of benign prostatic hyperplasia or neurogenic bladder. The clinical
      manifestations of obstructive uropathy range from little or no symptoms to acute
      renal failure. Because its prevalence increases with increasing age, the
      diagnosis and management of obstructive uropathy is particularly relevant to the
      geriatric population.

PMID- 19765492
TI  - Urinary incontinence in the elderly.
AB  - Urinary incontinence is a common clinical problem in the elderly population, and
      can affect men and women. Chronic incontinence can lead to impairments in overall
      functional status and is associated with significant negative effects on both
      overall and health-related quality of life. Careful clinical evaluation can be
      useful to differentiate among the various types of urinary incontinence, and can
      help to identify the potential cause of the condition. A wide variety of
      behavioral, pharmacologic, and surgical therapies are available to treat urinary
      incontinence, and these may be used alone or in combination. Treatment can help
      to improve or eliminate symptoms for many patients, leading to enhanced quality
      of life and improved functional status.

PMID- 19765493
TI  - Drug dosing in the elderly patients with chronic kidney disease.
AB  - Chronic kidney disease is a common disorder that affects many patients with a
      prevalence approaching 19 million people in the United States. Kidney failure and
      renal impairment is a common occurrence in the geriatric population. Most types
      of kidney diseases are chronic conditions and frequently manifest at the late
      stages of life. Epidemiologic studies suggest that older patients are at a
      greater risk for renal failure if the kidney experiences insults from ischemia or
      exposure to pharmacologic and diagnostic nephrotoxins. Pharmacologic management
      of most common diseases in elderly individuals is a difficult task, particularly
      in older individuals with chronic kidney disease. Thus, primary care providers
      must proceed with caution when prescribing drugs for elderly patients with kidney
      disease.

PMID- 19765494
TI  - Renal replacement therapy in the elderly.
AB  - Rates of chronic kidney disease and end-stage renal disease are increasing as the
      United States population ages. The elderly with chronic kidney disease or end
      stage renal disease face specific challenges with regard to medical care. Being
      of elderly age should not be a contraindication for initiation of renal
      replacement therapy. As the United States population ages, physicians will have
      to face many challenges associated with aging, whether medical, psychosocial, or
      ethical. This article discusses issues specific to the geriatric dialysis
      population.

PMID- 19765495
TI  - Ethical issues in the elderly with renal disease.
AB  - Despite the many technical advances in medical care and dialysis delivery,
      mortality and morbidity remain high in patients with end-stage renal disease.
      This is particularly true in older patients, who often have a great number of
      coexisting diseases. In this population, life expectancy and quality of life may
      be rather poor, raising a number of ethical issues about the decision of starting
      start or withdrawing renal replacement therapy. Unfortunately, clear behavior
      guidelines on these critical issues are still insufficient. Reasons for not
      starting dialysis include old age, neurologic impairment, end-stage organ failure
      other than the kidneys, metastatic cancer, multiple comorbidities, and patient or
      family refusal. Similar reasons often underlie dialysis withdrawal of dialysis.
      Often these difficult decisions are left to care givers and family members or
      surrogates, since only a minority of patients with severe medical conditions
      discuss end-of-life care before becoming mentally impaired. The final shared
      decision should be the result of weighing beneficence (to maximise maximize good)
      with non-maleficence (to not cause harm); in the presence of severe medical
      conditions and/or mental impairment, dialysis may represent a prolongation of
      death rather than life.

PMID- 19765496
TI  - Pounds Off Digitally study: a randomized podcasting weight-loss intervention.
AB  - BACKGROUND: As obesity rates rise, new weight-loss methods are needed. Little is
      known about the use of podcasting (audio files for a portable music player or
      computer) to promote weight loss, despite its growing popularity. DESIGN: A 12
      week RCT was conducted. SETTING/PARTICIPANTS: The study sample comprised
      overweight men and women (BMI=25-40 kg/m(2); n=78) in the Raleigh-Durham NC area.
      INTERVENTION: In 2008, participants were randomly assigned to receive 24 episodes
      of a currently available weight-loss podcast (control podcast) or a weight-loss
      podcast based on social cognitive theory (SCT) designed by the researchers
      (enhanced podcast) for 12 weeks. MAIN OUTCOME MEASURES: Weight was measured on a
      digital scale at baseline and follow-up. Both groups also completed
      questionnaires assessing demographic information, food intake, physical activity,
      and SCT constructs at the introductory and 12-week meetings. Additional
      questionnaires at the 12-week meeting assessed perceptions of the intervention.
      RESULTS: Data collection and analysis occurred in 2008 and intention-to-treat was
      used. Enhanced group participants (n=41) had a greater decrease in weight (-2.9+/
      3.5 kg enhanced group vs -0.3+/-2.1 control group; p<0.001 between groups) and
      BMI (-1.0+/-1.2 kg/m(2) enhanced group vs -0.1+/-0.7 kg/m(2) control group;
      p<0.001 between groups) than the control group (n=37) and had greater weight-loss
      related knowledge (p<0.05), elaboration (p<0.001), and user control (p<0.001) and
      less cognitive load (p<0.001). CONCLUSIONS: The results of this study suggest
      that the use of behavioral, theory-based podcasting may be an effective way to
      promote weight loss. TRIAL REGISTRATION: NCT00771095.

PMID- 19765497
TI  - Preventing weight gain: one-year results of a randomized lifestyle intervention.
AB  - BACKGROUND: Lifestyle interventions targeting prevention of weight gain may have
      better long-term success than when aimed at weight loss. Limited evidence exists
      about such an approach in the primary care setting. DESIGN: An RTC was conducted.
      SETTING/PARTICIPANTS: Participants were 457 overweight or obese patients (BMI=25
      40 kg/m(2), mean age 56 years, 52% women) with either hypertension or
      dyslipidemia, or both, from 11 general practice locations in The Netherlands.
      INTERVENTION: In the intervention group, four individual visits to a nurse
      practitioner (NP) and one feedback session by telephone were scheduled for
      lifestyle counseling with guidance of the NP using a standardized computerized
      software program. The control group received usual care from their general
      practitioner (GP). MAIN OUTCOME MEASURES: Changes in body weight, waist
      circumference, blood pressure, and blood lipids after 1 year (dropout <10%). Data
      were collected in 2006 and 2007. Statistical analyses were conducted in 2007 and
      2008. RESULTS: There were more weight losers and stabilizers in the NP group than
      in the general practitioner usual care (GP-UC) group (77% vs 65%; p<0.05). In
      men, mean weight losses were 2.3% for the NP group and 0.1% for the GP-UC group
      (p<0.05). Significant reductions occurred also in waist circumference but not in
      blood pressure, blood lipids, and fasting glucose. In women, mean weight losses
      were in both groups 1.6%. In the NP group, obese people lost more weight (-3.0%)
      than the non-obese (-1.3%; p<0.05). CONCLUSIONS: Standardized computer-guided
      counseling by NPs may be an effective strategy to support weight-gain prevention
      and weight loss in primary care, in the current trial, particularly among men.
      TRIAL REGISTRATION: The study was registered with the Netherlands Trial Register
      (NTR), www.trialregister.nl, study no. TC 1365.

PMID- 19765498
TI  - Cardiometabolic risk in younger and older adults across an index of ambulatory
      activity.
AB  - BACKGROUND: Pedometers are increasingly being used to assess population levels of
      physical activity and as motivational tools for individuals to increase their
      physical activity. To maximize their utility, a framework for classifying
      pedometer-determined activity into meaningful health-related categories is
      needed. PURPOSE: This study investigated whether a pedometer step index proposed
      by Tudor-Locke and Bassett can effectively group younger and older adults
      according to cardiometabolic health status. METHODS: Analyses (conducted in 2008)
      used cross-sectional data from the Childhood Determinants of Adult Health study
      (1793 adults aged 26-36 years; collected 2004-2006) and from the Tasmanian Older
      Adult Cohort study (1014 adults aged 50-80 years; collected 2002-2006).
      Participants wore a pedometer for 7 days and the prevalence of cardiometabolic
      health indicators, including the metabolic syndrome, elevated Pathobiological
      Determinants of Atherosclerosis in Youth risk scores, and elevated Framingham
      risk scores, was examined across the following step categories: sedentary (<
      5000); low-active (5000-7499); somewhat active (7500-9999); active (10,000
      12,499); and high-active (> or = 12,500). RESULTS: With the exception of younger
      men, individuals achieving > or = 5000 steps had a substantially lower prevalence
      of adverse cardiometabolic health indicators than those obtaining fewer steps.
      Differences in the prevalence of adverse indicators were generally modest across
      higher steps-per-day categories. However, younger men and women in the high
      active category had a substantially lower prevalence of some adverse health
      indicators. CONCLUSIONS: In general, the proposed index for classifying pedometer
      activity effectively distinguishes cardiometabolic health risk. Pedometers may be
      a useful tool for objectively identifying inactive individuals at greatest risk
      for poor cardiometabolic health.

PMID- 19765499
TI  - A walk (or cycle) to the park: active transit to neighborhood amenities, the
      CARDIA study.
AB  - BACKGROUND: Building on known associations between active commuting and reduced
      cardiovascular disease (CVD) risk, this study examines active transit to
      neighborhood amenities and differences between walking and cycling for
      transportation. METHODS: Year-20 data from the Coronary Artery Risk Development
      in Young Adults study (3549 black and white adults aged 38-50 years in 2005-2006)
      were analyzed in 2008-2009. Sociodemographic correlates of transportation mode
      (car-only, walk-only, any cycling, other) to neighborhood amenities were examined
      in multivariable multinomial logistic models. Gender-stratified multivariable
      linear or multinomial regression models compared CVD risk factors across transit
      modes. RESULTS: Active transit was most common to parks and public transit stops;
      walking was more common than cycling. Among those who used each amenity, active
      transit (walk-only and any cycling versus car-only transit) was more common in
      men and those with no live-in partner and less than full-time employment
      (significant ORs [95% CI] ranging from 1.56 [1.08, 2.27] to 4.54 [1.70, 12.14]),
      and less common in those with children. Active transit to any neighborhood
      amenity was associated with more favorable BMI, waist circumference, and fitness
      (largest coefficient [95% CI] -1.68 [-2.81, -0.55] for BMI, -3.41 [-5.71, -1.11]
      for waist circumference [cm], and 36.65 [17.99, 55.31] for treadmill test
      duration [seconds]). Only cycling was associated with lower lifetime CVD risk
      classification. CONCLUSIONS: Active transit to neighborhood amenities was related
      to sociodemographics and CVD risk factors. Variation in health-related benefits
      by active transit mode, if validated in prospective studies, may have
      implications for transportation planning and research.

PMID- 19765500
TI  - The built environment and physical activity levels: the Harvard Alumni Health
      Study.
AB  - BACKGROUND: Physical activity is associated with better health, but many
      individuals are insufficiently active. Modifying the built environment may be an
      approach capable of influencing population-wide levels of physical activity, but
      few data exist from longitudinal studies that can minimize bias from active
      people choosing activity-friendly neighborhoods. PURPOSE: This study aims to
      examine cross-sectional and longitudinal associations between the built
      environment and physical activity on a large scale. METHODS: This study examined
      cross-sectional associations between urban sprawl (mapping addresses to
      corresponding counties) and physical activity (self-reported) among men
      throughout the U.S. in 1993 and in 1988, and longitudinal associations between
      changes in exposure to urban sprawl for movers and physical activity, 1988-1993.
      Included were 4997 men (mean age, 70 years) in the 1993 cross-sectional study;
      4918 men in the 1988 cross-sectional study; and 3448 men in the longitudinal
      study, 1988-1993. Data were collected prospectively in 1988 and 1993, and
      analyses were performed in 2007-2008. RESULTS: In cross-sectional analyses, less
      sprawl was significantly associated with more walking OR, comparing least with
      most sprawling areas, for meeting physical activity recommendations by
      walking=1.38 [95% CI=1.09, 1.76] in 1993 and 1.53 [1.19, 1.96] in 1988). Less
      sprawl also was associated with lower prevalence of overweight (corresponding
      OR=0.79 [0.64, 0.98] in 1993 and 0.81 [0.66, 1.00] in 1988). However,
      longitudinal analyses assessing change did not show that decreasing sprawl was
      associated with increased physical activity or decreased BMI. CONCLUSIONS: These
      findings suggest that the cross-sectional results may reflect self-selection,
      rather than indicating that the built environment--as measured by urban sprawl-
      increases physical activity. However, the longitudinal findings were limited by
      small numbers of men changing residence and associated sprawl levels.

PMID- 19765501
TI  - Health-risk correlates of video-game playing among adults.
AB  - BACKGROUND: Although considerable research suggests that health-risk factors vary
      as a function of video-game playing among young people, direct evidence of such
      linkages among adults is lacking. PURPOSE: The goal of this study was to
      distinguish adult video-game players from nonplayers on the basis of personal and
      environmental factors. It was hypothesized that adults who play video games,
      compared to nonplayers, would evidence poorer perceptions of their health,
      greater reliance on Internet-facilitated social support, more extensive media
      use, and higher BMI. It was further hypothesized that different patterns of
      linkages between video-game playing and health-risk factors would emerge by
      gender. METHODS: A cross-sectional, Internet-based survey was conducted in 2006
      with a sample of adults from the Seattle-Tacoma area (n=562), examining health
      risks; media use behaviors and perceptions, including those related to video-game
      playing; and demographics. Statistical analyses conducted in 2008 to compare
      video-game players and nonplayers included bivariate descriptive statistics,
      stepwise discriminant analysis, and ANOVA. RESULTS: A total of 45.1% of
      respondents reported playing video games. Female video-game players reported
      greater depression (M=1.57) and poorer health status (M=3.90) than female
      nonplayers (depression, M=1.13; health status, M=3.57). Male video-game players
      reported higher BMI (M=5.31) and more Internet use time (M=2.55) than male
      nonplayers (BMI, M=5.19; Internet use, M=2.36). The only determinant common to
      female and male video-game players was greater reliance on the Internet for
      social support. CONCLUSIONS: A number of determinants distinguished video-game
      players from nonplayers, and these factors differed substantially between men and
      women. The data illustrate the need for further research among adults to clarify
      how to use digital opportunities more effectively to promote health and prevent
      disease.

PMID- 19765502
TI  - Breast cancer screening among Vietnamese Americans: a randomized controlled trial
      of lay health worker outreach.
AB  - BACKGROUND: Vietnamese-American women underutilize breast cancer screening.
      DESIGN: An RCT was conducted comparing the effect of lay health workers (LHWs)
      and media education (ME) to ME alone on breast cancer screening among these
      women. SETTING/PARTICIPANTS: Conducted in California from 2004 to 2007, the study
      included 1100 Vietnamese-American women aged > or = 40 years who were recruited
      through LHW social networks. Data were analyzed from 2007 to 2009. INTERVENTION:
      Both groups received targeted ME. The intervention group received two LHW
      educational sessions and two telephone calls. MAIN OUTCOME MEASURES: Change in
      self-reported receipt of mammography ever, mammography within 2 years, clinical
      breast examination (CBE) ever, or CBE within 2 years. RESULTS: The LHW+ME group
      increased receipt of mammography ever and mammography in the past 2 years (84.1%
      to 91.6% and 64.7% to 82.1%, p<0.001) while the ME group did not. Both ME (73.1%
      to 79.0%, p<0.001) and LHW+ME (68.1% to 85.5%, p<0.001) groups increased receipt
      of CBE ever, but the LHW+ME group had a significantly greater increase. The
      results were similar for CBE within 2 years. In multivariate analyses, LHW+ME was
      significantly more effective than ME for all four outcomes, with ORs of 3.62 (95%
      CI=1.35, 9.76) for mammography ever; 3.14 (95% CI=1.98, 5.01) for mammography
      within 2 years; 2.94 (95% CI=1.63, 5.30) for CBE ever; and 3.04 (95% CI=2.11,
      4.37) for CBE within 2 years. CONCLUSIONS: Lay health workers increased breast
      cancer screening among Vietnamese-American women.Future research should focus on
      how LHWs work and whether LHW outreach can be disseminated to other ethnic groups
      [corrected].

PMID- 19765503
TI  - Driving after binge drinking.
AB  - BACKGROUND: Although binge drinking is strongly associated with alcohol-impaired
      driving, little is known about the prevalence of or risk factors for driving
      after binge drinking. PURPOSE: The purpose of this study was to assess the
      prevalence of, and risk factors for, driving during or shortly after a specific
      binge drinking episode. METHODS: The data were analyzed in 2007 and 2008 from
      14,085 adults from 13 states in 2003 and 14 states in 2004 who reported binge
      drinking and answered an additional series of questions about binge drinking
      behaviors as part of the Behavioral Risk Factor Surveillance System survey. Binge
      drinking was defined as the consumption of five or more drinks during a drinking
      occasion. RESULTS: Overall, 11.9% of binge drinkers drove during or within 2
      hours of their most recent binge drinking episode. Those drinking in licensed
      establishments (bars, clubs, and restaurants) accounted for 54.3% of these
      driving episodes. Significant independent risk factors for driving after binge
      drinking included male gender (AOR = 1.75); being aged 35-54 or > or = 55 years
      compared to 18-34 years (AOR = 1.58 and 2.37, respectively); and drinking in bars
      or clubs compared to drinking in the respondent's home (AOR = 7.81). Drivers who
      drank most of their alcohol in licensed establishments consumed an average of 8.1
      drinks, and 25.7% of them consumed > or = 10 drinks. CONCLUSIONS: Because binge
      drinking and subsequent driving were common in establishments licensed to sell
      alcohol, and because licensing is conditional on responsible beverage service
      practices (i.e., not selling to intoxicated people), efforts to prevent impaired
      driving should focus on enforcing responsible beverage service in licensed
      establishments.

PMID- 19765504
TI  - Rear-seat motor vehicle travel in the U.S.: using national data to define a
      population at risk.
AB  - BACKGROUND: Recent studies suggest that the relative protection offered by rear
      seating in motor vehicle crashes has decreased, potentially reflecting
      disproportionate advancements in front-seat safety technology. Safe adaptation of
      advanced front-seat restraint systems for the rear-seat environment will require
      exposure data that are currently unavailable. PURPOSE: This study uses national
      data to quantify rear-seat occupancy patterns, restraint use, and annual travel
      exposure in the U.S. in order to support the development of advanced crash
      protection systems for rear-seat motor vehicle occupants. METHODS: Data from the
      2000-2006 National Automotive Sampling System Crashworthiness Data System and
      2001 National Household Transportation Survey were analyzed in 2008 to quantify
      occupancy patterns (e.g., seat position, restraint use) and annual person-trips
      for rear-seat passengers in the U.S. RESULTS: The overall proportion of person
      trips by rear-seat occupants is relatively low (12.9%); however national at-risk
      exposure remains significant (approximately 39 billion annual person-trips).
      Annual rear-seat travel exposure is similar among children < or = 12 years and
      adults (18.9 vs 19.1 billion person-trips) despite the fact that children are
      proportionally much more likely to ride in rear positions (79.3% vs 7.4%).
      Restraint use among adult rear-seat occupants was also much lower than among
      front-seat occupants (50.4% vs 82.2%). CONCLUSIONS: While rear-seat occupancy is
      relatively low compared with front-seat occupancy at-risk rear-seat travel by
      both child and adult passengers in the U.S. remains significant. Restraint use by
      rear-seat occupants is much lower than that among front-seat passengers,
      particularly among adults and older children, substantially increasing injury
      risk. Development of future crash protection systems for rear-seat passengers
      must account for these exposure patterns to ensure safe and effective integration
      into production vehicles.

PMID- 19765505
TI  - Telephone recruitment into a randomized controlled trial of quitline support.
AB  - BACKGROUND: Only 1%-7% of adult smokers use quitlines annually. Active telephone
      recruitment may increase utilization and enroll new groups of quitline users.
      PURPOSE: This study aimed to (1) determine the proportion of adult daily smokers
      actively recruited by telephone to quitline support; (2) calculate the cost per
      smoker recruited; and (3) compare the characteristics of participants to smokers
      in the New South Wales (NSW, Australia) general population. METHODS: Between
      September 2005 and April 2007, 1562 adult daily smokers randomly selected from
      the electronic NSW telephone directory were recruited into an RCT. The proportion
      of smokers and the cost per smoker recruited were examined. Participants were
      compared to NSW adult daily smokers from the NSW Population Health Survey and the
      Centre for Health Research & Psycho-oncology Smoking Community Survey. Analysis
      was completed in 2008. RESULTS: More than half (52%) of eligible smokers
      contacted by telephone were recruited into cessation support. The cost per smoker
      recruited was AU$71 (US$59). Active telephone recruitment successfully enrolled
      smokers who are currently under-represented among quitline users. For instance,
      more than two thirds (68%) of participants were not intending to quit within 1
      month. Compared with NSW adult daily smokers, participants were significantly
      more likely to be older; more highly educated; married/living with partner or
      divorced/separated; a nonmetropolitan resident; more nicotine dependent; more
      ready to quit; and have fewer household members. Participants were significantly
      less likely to live with a smoker than were NSW adult daily smokers. CONCLUSIONS:
      Active telephone recruitment has the potential to substantially increase the
      proportion of smokers using quitline services at a reasonable cost. This method
      also engages smokers currently under-represented in quitline populations.

PMID- 19765507
TI  - The effectiveness of worksite nutrition and physical activity interventions for
      controlling employee overweight and obesity: a systematic review.
AB  - This report presents the results of a systematic review of the effectiveness of
      worksite nutrition and physical activity programs to promote healthy weight among
      employees. These results form the basis for the recommendation by the Task Force
      on Community Preventive Services on the use of these interventions. Weight
      related outcomes, including weight in pounds or kilograms, BMI, and percentage
      body fat were used to assess effectiveness of these programs. This review found
      that worksite nutrition and physical activity programs achieve modest
      improvements in employee weight status at the 6-12-month follow-up. A pooled
      effect estimate of -2.8 pounds (95% CI=-4.6, -1.0) was found based on nine RCTs,
      and a decrease in BMI of -0.5 (95% CI=-0.8, -0.2) was found based on six RCTs.
      The findings appear to be applicable to both male and female employees, across a
      range of worksite settings. Most of the studies combined informational and
      behavioral strategies to influence diet and physical activity; fewer studies
      modified the work environment (e.g., cafeteria, exercise facilities) to promote
      healthy choices. Information about other effects, barriers to implementation,
      cost and cost effectiveness of interventions, and research gaps are also
      presented in this article. The findings of this systematic review can help inform
      decisions of employers, planners, researchers, and other public health decision
      makers.

PMID- 19765506
TI  - Meta-analysis of workplace physical activity interventions.
AB  - CONTEXT: Most adults do not achieve adequate physical activity levels. Despite
      the potential benefits of worksite health promotion, no previous comprehensive
      meta-analysis has summarized health and physical activity behavior outcomes from
      such programs. This comprehensive meta-analysis integrated the extant wide range
      of worksite physical activity intervention research. EVIDENCE ACQUISITION:
      Extensive searching located published and unpublished intervention studies
      reported from 1969 through 2007. Results were coded from primary studies. Random
      effects meta-analytic procedures, including moderator analyses, were completed in
      2008. EVIDENCE SYNTHESIS: Effects on most variables were substantially
      heterogeneous because diverse studies were included. Standardized mean difference
      (d) effect sizes were synthesized across approximately 38,231 subjects.
      Significantly positive effects were observed for physical activity behavior
      (0.21); fitness (0.57); lipids (0.13); anthropometric measures (0.08); work
      attendance (0.19); and job stress (0.33). The significant effect size for
      diabetes risk (0.98) is less robust given small sample sizes. The mean effect
      size for fitness corresponds to a difference between treatment minus control
      subjects' means on VO2max of 3.5 mL/kg/min; for lipids, -0.2 on the ratio of
      total cholesterol to high-density lipoprotein; and for diabetes risk, -12.6 mg/dL
      on fasting glucose. CONCLUSIONS: These findings document that some workplace
      physical activity interventions can improve both health and important worksite
      outcomes. Effects were variable for most outcomes, reflecting the diversity of
      primary studies. Future primary research should compare interventions to confirm
      causal relationships and further explore heterogeneity.

PMID- 19765508
TI  - A recommendation to improve employee weight status through worksite health
      promotion programs targeting nutrition, physical activity, or both.

PMID- 19765509
TI  - Effectiveness of multicomponent programs with community mobilization for reducing
      alcohol-impaired driving.
AB  - A systematic review was conducted to determine the effectiveness and economic
      efficiency of multicomponent programs with community mobilization for reducing
      alcohol-impaired driving. The review was conducted for the Guide to Community
      Preventive Services (Community Guide). Six studies of programs qualified for the
      review. Programs addressed a wide range of alcohol-related concerns in addition
      to alcohol-impaired driving. The programs used various crash-related outcomes to
      measure their effectiveness. Two studies examined fatal crashes and reported
      declines of 9% and 42%; one study examined injury crashes and reported a decline
      of 10%; another study examined crashes among young drivers aged 16-20 years and
      reported a decline of 45%; and one study examined single-vehicle late-night and
      weekend crashes among young male drivers and reported no change. The sixth study
      examined injury crashes among underage drivers and reported small net reductions.
      Because the actual numbers of crashes were not reported, percentage change could
      not be calculated. According to Community Guide rules of evidence, the studies
      reviewed here provided strong evidence that carefully planned, well-executed
      multicomponent programs, when implemented in conjunction with community
      mobilization efforts, are effective in reducing alcohol-related crashes. Three
      studies reported economic evidence that suggests that such programs produce cost
      savings. The multicomponent programs generally included a combination of efforts
      to limit access to alcohol (particularly among youth), responsible beverage
      service training, sobriety checkpoints or other well-defined enforcement efforts,
      public education, and media advocacy designed to gain the support of both
      policymakers and the general public for reducing alcohol-impaired driving.

PMID- 19765510
TI  - Reconciling the construct of walking in physical activity and transportation
      research.

PMID- 19765511
TI  - The cooperative medical extension program: translation of medical best practices
      to practicing primary care providers.

PMID- 19765512
TI  - Opportunities and challenges in behavioral informatics observations on the Pounds
      Off Digitally study.

PMID- 19765513
TI  - Video games: play or "playlike activity"?

PMID- 19765514
TI  - Editorial: "formula-driven" versus "lab-driven" massive transfusion protocols: at
      a state of clinical equipoise.

PMID- 19765515
TI  - Controversy in trauma resuscitation: do ratios of plasma to red blood cells
      matter?
AB  - Since a report in October 2007 of dramatic improvements in trauma mortality in a
      military population when massive transfusion of red blood cells (RBC) was
      accompanied by plasma replacement at 1:1 proportions, interest in the plasma-to
      RBC ratio during resuscitation in both the trauma and transfusion communities has
      been intense. Over the 7-month period from August 2008 through February 2009, a
      further 9 major studies examining experience with plasma replacement in massively
      transfused civilian trauma patients have been published. This flood of
      observational studies is likely to continue. In this review, the authors examine
      the findings of these initial studies, highlighting the epidemiologic and
      analytic methodologies used, and the likely influence of these methodologies on
      the reported outcomes.

PMID- 19765517
TI  - Filling a gap in transfusion medicine education and research.
AB  - After the outbreak of the HIV/AIDS epidemic, attention was focused on the
      restructuring and reorganization of nationally supported safe and sustainable
      blood supply systems. Networking and human capacity building in transfusion
      medicine were developed through World Health Organization initiatives.
      Educational materials were created for the core elements of the blood transfusion
      chain. However, the management aspects of transfusion medicine as well as applied
      health science research in transfusion medicine were not addressed. In 2000, the
      World Health Organization initiated the creation of the Academic Institute for
      International Development of Transfusion Medicine (IDTM). This would focus on the
      development of a postgraduate master's course in management of transfusion
      medicine (MMTM) and the development of research programs for transfusion medicine
      related health sciences. The Academic Institute IDTM was created at the
      University of Groningen Faculty of Medical Sciences, The Netherlands. The MMTM
      course was thus established, and since September 2007 fourteen fellows from
      economically restricted countries have entered the course.

PMID- 19765516
TI  - The role of neutrophils in the pathogenesis of transfusion-related acute lung
      injury.
AB  - Transfusion-related acute lung injury (TRALI) is the major cause of transfusion
      related morbidity and mortality, world wide. Efforts to reduce or eliminate this
      serious complication of blood transfusion are hampered by an incomplete
      understanding of its pathogenesis. Currently, TRALI is thought to be mediated by
      donor alloantibodies directed against host leukocytes or the result of 2 distinct
      clinical events. For both proposed mechanisms, the neutrophil is the key effector
      cell. This article reviews TRALI pathophysiology, explores the role of the
      neutrophil, details practical information for appropriate diagnosis and promotes
      further studies into the pathogenesis of TRALI.

PMID- 19765518
TI  - Blood group antigens and normal red blood cell physiology: a Canadian blood
      services research and development symposium.

PMID- 19765519
TI  - Transfusion medicine in Chicago, before and after the "blood bank".
AB  - Although history states correctly that Bernard Fantus coined the name "blood
      bank" in Chicago in 1937, his was only one of many contributions of Midwest
      America to the new therapy of blood transfusion. Chicago was at the center of the
      movement before and after then, anticipating the modern era with the first
      practical method for direct donor-to-recipient transfusion and staging a secret
      clinical trial of cadaver blood. That successful trial of cadaver blood may have
      presaged the first functional cadaver kidney transplant, performed at the same
      hospital several years later. Modern-day technologies for blood collection,
      transfusion, and safety testing also have many roots in Chicago.

PMID- 19765520
TI  - Nearly two decades have passed since the seminal reporting of the first
      endovascular repair of an infrarenal aortic aneurysm using a homemade stent graft
      in 1991.

PMID- 19765521
TI  - Current status of investigational devices for EVAR: similarities and differences.
AB  - Improvements in the design of endovascular grafts are based on lessons learned
      from difficulties encountered with prior-generation devices. The most common
      difficulties in device design relate to how the device is delivered and how it
      can safely and durably fix the aneurysm. This concept is especially true in
      patients with difficult anatomy. Difficult anatomy, such as small, calcified,
      tortuous access vessels and short angulated sealing zones, continue to challenge
      engineers. Currently, the US Food and Drug Administration has approved eight
      endovascular devices for the treatment of aortic aneurysms: five for abdominal
      aortic aneurysms and three for thoracic aortic aneurysms. Compared to the first
      generation devices approved in 1999, current devices have smaller and more
      flexible delivery systems. The devices themselves are more flexible and have
      better fixation than prior-generation devices. This article will focus on the
      next generation of devices that are not yet approved, but currently under
      investigation in the United States.

PMID- 19765522
TI  - Fenestrated and branched stent grafts for repair of complex aortic aneurysms.
AB  - Open surgical repair of complex aortic aneurysms, such as juxtarenal or
      thoracoabdominal aortic aneurysms, is a highly demanding procedure. They
      frequently require major surgical exposure through both the thoracic and the
      abdominal cavities, suprarenal or supraceliac aortic cross-clamping, and exposure
      of the visceral and renal arteries. Endovascular aortic repair and thoracic
      endovascular aortic repair have become the mainstay of treatment for infrarenal
      abdominal aortic aneurysms and descending thoracic aneurysms. However, the
      obvious need to maintain perfusion of the visceral and renal arteries has limited
      application of endovascular techniques to treatment of more complex aneurysms.
      Fenestrated and branched stent grafts are being developed to address this need
      and enable repair of complex aneurysms involving branch vessels exclusively using
      minimally invasive techniques. Although these devices remain investigational in
      the United States, they have recently become commercially available in other
      countries and play an increasing role in the management of complex aortic
      aneurysms.

PMID- 19765523
TI  - Hybrid procedures for thoracoabdominal aortic aneurysms.
AB  - Treatment of thoracic aortic pathology has been rapidly changing in the 5 years
      since US Food and Drug Administration approval of thoracic stent grafts. Although
      not specifically evaluated in any of the major clinical trials to date,
      adjunctive techniques are being increasingly used to expand the applicability of
      stent-graft technology to patients with more extensive thoracoabdominal aortic
      aneurysms and dissections. Details of procedural techniques have been delineated
      by several aortic specialists, resulting in a trend toward standardization of
      effective strategies. Despite this trend, significant variability is evident in
      the outcomes of reported series. The objective of this article is to analyze
      published reports of hybrid procedures involving complete visceral debranching of
      the aorta and endovascular exclusion of the thoracoabdominal aortic aneurysms.

PMID- 19765524
TI  - TEVAR for acute uncomplicated aortic dissection: immediate repair versus medical
      therapy.
AB  - Medical management remains the standard treatment modality for acute
      uncomplicated descending aortic dissections. Intervention (by either open surgery
      or an endovascular approach) is currently reserved for patients who present with
      or subsequently develop complications (ie, complicated dissections). Despite the
      success of medical therapy in the acute management of uncomplicated dissection,
      long-term morbidity and mortality are far from ideal. The introduction of
      thoracic endovascular aortic repair (TEVAR) has been associated with reductions
      in morbidity and mortality in the treatment of complicated dissections. There is
      limited data regarding TEVAR for acute uncomplicated dissections. Early results
      from the INSTEAD (Investigation of Stent Grafts in Patients with Type B Aortic
      Dissection) trial, a randomized trial for TEVAR in subacute/chronic uncomplicated
      dissections, were not favorable. The ADSORB (Acute Uncomplicated Aortic
      Dissection Type B: Evaluating Stent-Graft Placement or Best Medical Treatment
      Alone) trial, a randomized trial for TEVAR in acute dissections, is currently
      underway. Nonetheless, current data available, including multiple reports
      proposing a variety of predictive factors, suggest that there may be a subset of
      higher-risk patients with acute uncomplicated dissections who could benefit from
      TEVAR.

PMID- 19765525
TI  - Coverage of the celiac artery during TEVAR: is it ever appropriate?
AB  - Adequate seal at the proximal and distal extent of stent grafts in the aorta is
      paramount to the success of thoracic endovascular aortic repair (TEVAR).
      Thoracoabdominal aneurysms pose a formidable challenge given their extension into
      the arch branches proximally and the visceral segment distally. Extension of the
      landing zone of even 3 to 5 mm can possibly increase the durability of the stent
      graft and may decrease the chances of future migration or collapse. Although
      coverage of the subclavian artery to extend the proximal landing zone has been
      met with initial success, the outcome of coverage of the celiac axis in order to
      extend the distal landing zone has not been as well studied. Because of the
      abundance of rich collateral vessels in the foregut, it has been perceived as a
      potentially safe practice. However, careful angiographic anatomic delineation and
      patient selection is vital to determine whether concomitant revascularization
      procedures are warranted.

PMID- 19765526
TI  - Management of the left subclavian artery during TEVAR.
AB  - The proximity of thoracic aortic pathologies to the left subclavian artery has
      occasionally required intentional coverage of this vessel. With increased
      collective experience with thoracic endovascular techniques, indications for
      revascularization in this setting have evolved. Coverage of the left subclavian
      artery without revascularization has been associated with left arm claudication,
      spinal cord ischemia, posterior circulation strokes, and, in certain instances,
      myocardial ischemia. The occurrence of these events has not been uniform and, in
      some patients, the left subclavian artery can be covered without significant
      clinical sequelae. In this review, we discuss the incidence of these
      complications, their risk factors, and indications for elective revascularization
      of the left subclavian artery during thoracic endovascular aortic repair.

PMID- 19765527
TI  - Management of type II endoleaks: preoperative versus postoperative versus
      expectant management.
AB  - Type II endoleak is a common phenomenon after endovascular aneurysm repair (EVAR)
      for abdominal aortic aneurysm (AAA). Most type II endoleaks are innocuous and
      transient and therefore do not require intervention. However, particularly
      persistent endoleaks could lead to aneurysm enlargement and delayed aortic
      rupture. Decreasing the occurrence rates of type II endoleaks can be attempted
      with prophylactic occlusion of the inferior mesenteric, hypogastric, and lumbar
      arteries. Although the efficacy and clinical benefit of prophylactic occlusion of
      aortic branches prior to EVAR or during the endovascular repair remain
      controversial, we anticipate an increased use of intraoperative embolization
      techniques. A reasonable treatment strategy in patients with type II endoleak may
      be to intervene in cases of increasing aneurysm size or if the endoleak does not
      resolve spontaneously within 6 months. Translumbar embolization has been shown to
      be more effective than transarterial embolization. An alternative embolization
      technique is transcaval embolization, which has shown success rates comparable to
      translumbar embolization. Type II endoleaks can also be treated during
      laparoscopy or laparotomy, but these techniques are more invasive and should be
      used only after failure of embolization techniques.

PMID- 19765528
TI  - Using IVUS during EVAR and TEVAR: improving patient outcomes.
AB  - Intravascular ultrasonography (IVUS) provides immediate and dynamic imaging of
      aortic pathology that can be helpful in treating aortic pathology. IVUS has been
      shown to reduce the need for contrast imaging during endovascular reconstruction
      for both infrarenal and thoracic aortic endografting. We provide a technique and
      rationale for routine use of IVUS during endovascular abdominal aneurysm repair
      to reduce contrast load, fluoroscopy time, and complications that ultimately can
      improve patient outcomes.

PMID- 19765529
TI  - Technical tips for EVAR for ruptured AAA.
AB  - Endovascular treatment of ruptured abdominal aortic aneurysms is associated with
      decreased morbidity and mortality when compared to the open surgical approach,
      yet, there are several fundamental obstacles to our ability to offer these
      endovascular techniques to many patients with ruptured aneurysms. This article
      will focus on the technical aspects of endovascular aneurysm repair for rupture
      aneurysms, with particular attention on developing a standardized
      multidisciplinary approach that will address some practical issues, such as the
      need for preoperative computed tomography, choice of anesthesia, percutaneous
      access versus surgical exposure of the femoral arteries, use of aortic occlusion
      balloons, bifurcated versus aorto-uniiliac stent grafts, adjunctive procedures,
      diagnosis and treatment of abdominal compartment syndrome, and conversion to open
      surgical repair.

PMID- 19765530
TI  - Strategies for detection and prevention of spinal cord ischemia during TEVAR.
AB  - Spinal cord ischemia (SCI) is one of the most feared complications after
      treatment of thoracic aortic diseases. Based on limited evidence from clinical
      trials of investigational devices the incidence appears to be lower in
      endovascular compared to open thoracic aortic repairs. To date, several clinical
      and procedural factors have been associated with an increased risk of SCI,
      including the type of aortic pathology, length of endograft coverage, and
      perioperative hypotension. The treatment options mostly consist of spinal fluid
      drainage and systemic blood pressure elevation in an effort to maximize spinal
      cord perfusion. In this article, we review the risk factors for development of
      SCI, some diagnostic tests that may allow for its earlier detection, and
      potential strategies for its prevention.

PMID- 19765531
TI  - Hypogastric artery preservation during endovascular aortic aneurysm repair: is it
      important?
AB  - Endovascular repair of aortoiliac artery aneurysm is a safe and effective
      treatment strategy. Selective hypogastric artery embolization with coils may be
      necessary to allow the endograft to anchor in the aneurysm-free external iliac
      artery, thereby eliminating hypogastric endoleak into the aortoiliac aneurysm.
      Considerable controversy exists regarding the safety of intentional occlusion of
      the hypogastric artery. Proximal occlusion of a hypogastric artery with embolic
      coils typically produces little or no clinical symptoms due to well
      collateralized pelvic arterial networks. On the other hand, significant
      complications, such as colonic ischemia, spinal cord paralysis, buttock
      claudication, or erectile dysfunction are well-recognized adverse events after
      hypogastric artery embolization. This article examines the natural history of
      hypogastric artery embolization as well as clinical data regarding the safety and
      complications following this procedure. Clinical studies regarding risk factors
      that might contribute to ischemic complication following hypogastric artery
      embolization are presented. Lastly, treatment strategies to preserve the
      hypogastric artery thereby obviating the need for hypogastric artery embolization
      are discussed.

PMID- 19765532
TI  - Proximal migration and endoleak: impact of endograft design and deployment
      techniques.
AB  - Repair of abdominal aortic aneurysms by endovascular means is the preferred
      method in most patients. Despite its popularity, questions remain about the long
      term efficacy and durability. Proximal migration and endoleak are associated with
      significant morbidity and mortality, and are two of the most important factors in
      achieving a successful outcome. The technology associated with endovascular
      grafts continues to evolve rapidly, as does our understanding of ideal deployment
      techniques. Both can impact the incidence of proximal migration as well as
      endoleak and must be optimized to achieve ideal clinical outcomes.

PMID- 19765533
TI  - From glycosylation to glycosylation diseases.

PMID- 19765534
TI  - CDG nomenclature: time for a change!

PMID- 19765535
TI  - Editorial for special issue neuromathematics of vision.

PMID- 19765536
TI  - Making an impact.

PMID- 19765537
TI  - Pulmonary valve papillary fibroelastoma.

PMID- 19765538
TI  - Pneumopericardium.

PMID- 19765539
TI  - Congenital partial absence of the left pericardium suspected on the classical
      chest X-ray.

PMID- 19765540
TI  - Pancoast hydatid cyst leading to horner syndrome: thoracic hydatidosis.

PMID- 19765543
TI  - Transmissibility, by Glossina morsitans morsitans, of Trypanosoma congolense
      strains during the acute and chronic phases of infection.
AB  - In order to verify whether chronic trypanosomal infections can affect the
      transmissibility of Trypanosoma congolense by tsetse flies, batches of Glossina
      morsitans morsitans were fed on mice infected with the same level of parasitemia
      (10(8.1)trypanosomes/ml of blood) of two cloned low virulent T. congolense
      strains during the acute and the chronic phases of infection. Results showed that
      the proportions of procyclic infections in flies that were fed during the acute
      phase (32.6% and 45.4% for isolates 1 and 2, respectively) were significantly
      higher (chi(2)=4.7, P<0.05 and chi(2)=23.7, P<0.0001, respectively) compared to
      the proportions of procyclic infections of flies fed during the chronic phase of
      infection (18.8% and 14.9% for isolates 1 and 2, respectively). Similarly the
      proportions of metacyclic infections in flies fed during the acute phase (32.6%
      and 45.4% for isolates 1 and 2, respectively) were significantly higher
      (chi(2)=6.3, P<0.05 and chi(2)=23.7, P<0.0001, respectively) compared to the
      proportions of metacyclic infections in flies fed during the chronic phase of
      infection (16.8% and 14.9% for isolates 1 and 2, respectively). No significant
      difference was found in the maturation rate of both strains during the acute
      phase compared to the chronic phase of infection (P>0.05). The results of this
      study suggest that T. congolense loses part of its transmissiblity by tsetse
      flies during the chronic phase of infection.

PMID- 19765542
TI  - Schistosoma mansoni infection in a rural area of the Jequitinhonha Valley, Minas
      Gerais, Brazil: analysis of exposure risk.
AB  - This study examines the relative contribution of age-specific total IgE levels,
      eosinophils and water contact behavior to the prevalence and intensity (geometric
      mean egg counts) of Schistosoma mansoni infection in the poor rural population of
      Virgem das Gracas in northern Minas Gerais State. In bivariate analysis, age was
      strongly correlated with both prevalence and intensity of infection, while
      eosinophil levels with prevalence only (p<0.0001); IgE levels and 5 demographic
      and socioeconomic variables were moderately correlated with prevalence (p<0.05),
      as were number of persons per room and TBM (total body minutes) with egg counts.
      In multivariate analysis, after controlling for demographic and socioeconomic
      factors, only total IgE levels were significantly correlated with both prevalence
      (p=0.248, 95% CI=1.01-1.11) and intensity (p=0.0217, 95% CI=0.01-0.14) of
      infection and eosinophil levels with prevalence (p=0.0005, 95% CI=1.07-1.24).
      Although any causal relationship cannot be confirmed by a cross-sectional study,
      we demonstrated an associated decrease in prevalence and intensity of S. mansoni
      infection with increased IgE levels.

PMID- 19765544
TI  - Minocycline attenuates 5-fluorouracil-induced small intestinal mucositis in mouse
      model.
AB  - Minocycline exerts anti-inflammatory and anti-apoptotic effects distinct from its
      antimicrobial function. In this study we investigated the effect of this drug on
      chemotherapy-induced gut damage. Body weight loss results, diarrhea scores, and
      villi measurements showed that minocycline attenuated the severity of intestinal
      mucositis induced by 5-fluorouracil (5-FU). Minocycline repressed the expression
      of TNF-alpha, IL-1beta, and iNOS, decreased the apoptotic index, and inhibited
      poly(ADP-ribose) polymerase-1 (PARP-1) activity in the mouse small intestine. In
      vitro experiments showed that minocycline suppressed the upregulation of PARP-1
      activity in enterocyte IEC-6 cells treated with 5-FU. In addition, minocycline
      treatment appeared to enhance the antitumor effects of 5-FU in tumor CT-26
      xenograft mice. Our results indicate that minocycline protects mice from gut
      injury induced by 5-FU and enhances the antitumor effects of 5-FU in xenograft
      mice. These observations suggest that minocycline treatment may benefit patients
      undergoing standard cancer chemotherapy by alleviating chemical-associated
      intestinal mucositis.

PMID- 19765545
TI  - From IL-15 to IL-33: the never-ending list of new players in inflammation. Is it
      time to forget the humble aspirin and move ahead?
AB  - The study of the inflammatory response has seen a tremendous expansion over the
      last 30 years. Advancements in technology and better knowledge of the
      ethiopathogenesis of several inflammatory conditions have facilitated this
      process allowing researchers to almost reach the core of problem. Thus, we now
      know that inflammation can be manifested in many different ways depending on the
      context that has elicited it. Viral and infectious, allergic and autoimmune,
      carcinogenic and resolutive are just a few examples of how inflammation can
      disguise itself. However, and most intriguingly, it appears that the more we try
      to discover "an ideal target" and delineate borders for a specific class of
      inflammatory conditions the more we find similarities, overlaps or often links
      that we did not predict. These somehow disappointing findings have pushed
      researchers towards a frantic search for new and more "reliable" targets. As
      result, we have recently seen a surge of many novel mediators of inflammation. If
      we just limit our focus to inflammatory cytokines, the main topic of this
      commentary, the list seems never-ending: IL-15, IL-17, IL-18, IL-21, IL-22, IL
      23, IL-27 and IL-33. Are these cytokines destined to supersede prostaglandins and
      other autacoids for their key role in inflammation? Are we going to see a cheap
      and effective alternative to aspirin on the supermarket shelves in the next few
      years? Here we summarize the most recent findings on the biological effects of
      these new inflammatory cytokines and discuss how these discoveries might
      influence our current view on therapeutic approaches to treat inflammation.

PMID- 19765546
TI  - Efficacy of ST1968 (namitecan) on a topotecan-resistant squamous cell carcinoma.
AB  - ST1968 (namitecan), a novel 7-modified hydrophilic camptothecin, was found to be
      effective against tumor models relatively resistant to topotecan and irinotecan.
      Based on this observation, this study was designed to investigate the cellular
      and antitumor effects of ST1968 in a subline of A431, squamous cell carcinoma,
      selected for resistance to topotecan (A431/TPT). This model was characterized by
      a slow growth rate, associated with downregulation of EGFR and topoisomerase I.
      In contrast to other camptothecins (SN38 and gimatecan), ST1968 was able to
      overcome almost completely the resistance at cellular level. The cellular
      pharmacokinetics indicated a comparable accumulation and retention of ST1968 in
      sensitive and resistant cells, in spite of expression of the efflux transporter,
      P-glycoprotein, in resistant cells. The uptake and retention of topotecan were
      dramatically reduced in both tumor cell lines, but more evident in the resistant
      one. In contrast to topotecan, ST1968 retained an outstanding efficacy in vivo
      against the resistant tumor (A431/TPT). The results are consistent with the
      interpretation that ST1968 was able to overcome the most relevant mechanisms
      associated with the development of topotecan resistance (i.e., slow proliferation
      and target downregulation) owing to its peculiar pharmacokinetic behaviour.

PMID- 19765547
TI  - Modulation of human UMP/CMP kinase affects activation and cellular sensitivity of
      deoxycytidine analogs.
AB  - Deoxycytidine analogs are an important class of clinically active antiviral and
      anticancer agents. The stepwise phosphorylation of these analogs to triphosphate
      metabolites is crucial for biological action. Human UMP/CMP kinase (UMP/CMPK;
      cytidylate kinase; EC 2.7.4.14) is thought to be responsible for phosphorylation
      of UMP, CMP, and dCMP and may also play an important role in the activation of
      pyrimidine analogs. However, no evidence has verified this notion in intact
      cells. In this study we explored the functional roles of UMP/CMPK in natural
      pyrimidine synthesis and metabolism of deoxycytidine analogs, as well as 5-FU in
      HeLa S3 and HCT8 cells. The amounts of UMP/CMPK protein in different cell lines
      correlated with UMP, CMP, and dCMP kinase activities and amounts of UMP/CMPK RNA.
      Modulation of UMP/CMPK by overexpression or down-regulation had no impact on
      natural pyrimidine nucleotides and cell growth. However, down-regulating UMP/CMPK
      expression by siRNA led to a decrease in the formation of the triphosphate
      metabolites, resulting in cellular resistance to these analogs. More diphosphate
      and triphosphate metabolites of deoxycytidine analogs were detected and cellular
      sensitivity to these agents was increased in the UMP/CMPK-overexpressing cells.
      This study indicates that the second step enzyme (UMP/CMPK) is responsible for
      the phosphorylation of pyrimidine analogs and also has an impact on cellular
      sensitivity to these analogs in those cell lines.

PMID- 19765548
TI  - Astrocytes in the damaged brain: molecular and cellular insights into their
      reactive response and healing potential.
AB  - Long considered merely a trophic and mechanical support to neurons, astrocytes
      have progressively taken the center stage as their ability to react to acute and
      chronic neurodegenerative situations became increasingly clear. Reactive
      astrogliosis starts when trigger molecules produced at the injury site drive
      astrocytes to leave their quiescent state and become activated. Distinctive
      morphological and biochemical features characterize this process (cell
      hypertrophy, upregulation of intermediate filaments, and increased cell
      proliferation). Moreover, reactive astrocytes migrate towards the injured area to
      constitute the glial scar, and release factors mediating the tissue inflammatory
      response and remodeling after lesion. A novel view of astrogliosis derives from
      the finding that subsets of reactive astrocytes can recapitulate stem
      cell/progenitor features after damage, fostering the concept of astroglia as a
      promising target for reparative therapies. But which biochemical/signaling
      pathways modulate astrogliosis with respect to both the time after injury and the
      type of damage? Are reactive astrocytes overall beneficial or detrimental for
      neuroprotection and tissue regeneration? This debate has been animating this
      research field for several years now, and an integrated view on the results
      obtained and the possible future perspectives is needed. With this Commentary
      article we have attempted to answer the above-mentioned questions by reviewing
      the current knowledge on the molecular mechanisms controlling and sustaining the
      reaction of astroglia to injury and its stem cell-like properties. Moreover, the
      cellular/molecular mechanisms supporting the detrimental or beneficial features
      of astrogliosis have been scrutinized to gain insights on possible
      pharmacological approaches to enhance astrocyte neuroprotective activities.

PMID- 19765549
TI  - Investigation of anti-leukemia molecular mechanism of ITR-284, a carboxamide
      analog, in leukemia cells and its effects in WEHI-3 leukemia mice.
AB  - ITR-284, a potent anti-leukemia agent of carboxamide derivative, has been shown
      to inhibit the proliferation of leukemia cells. In this study, the underlying
      molecular mechanisms in vitro and anti-leukemia activity in vivo of ITR-284 were
      investigated. ITR-284 reduced the cell viability and induced apoptosis in HL-60
      and WEHI-3 leukemia cells. Following exposure of cells to 30 nM of ITR-284, there
      is a time-dependent decrease in the mitochondrial membrane potential
      (DeltaPsi(m)) and an increase in the reactive oxygen species (ROS). ITR-284
      treatment also caused a time-dependent increase of Fas/CD95, cytosolic cytochrome
      c, cytosolic active form of caspase-8/-9/-3, cytosolic Apaf-1 and Bax, and the
      decrease of Bcl-2. However, the ITR-284-induced caspase-8/-9 and -3 activities
      can be blocked by pan-caspase inhibitor (Z-VAD-FMK). In addition, the anti
      leukemia effects of ITR-284 in vivo were further evaluated in BALB/c mice
      inoculated with WEHI-3 cells. Orally treatment with ITR-284 (2 and
      10mg/kg/alternate day for 7 times) increased the survival rate and prevented the
      loss of body weight in leukemia mice. The enlargement of spleen and infiltration
      of immature myeloblastic cells into spleen red pulp were significantly reduced in
      ITR-284-treated mice compared with control mice. Moreover, ITR-284 application
      can enhance the anti-leukemia effect of all-trans retinoic acid (ATRA). These
      results revealed that ITR-284 acted against both HL-60 and WEHI-3 in vitrovia
      both intrinsic and extrinsic apoptotic signaling pathways, and exhibited an anti
      leukemic effect in a WEHI-3 orthotopic mice model of leukemia.

PMID- 19765550
TI  - Mechanisms involved in phosphatidylinositol 3-kinase pathway mediated up
      regulation of the mu opioid receptor in lymphocytes.
AB  - Despite the substantial progress made in understanding initiation expression of
      the MOR gene in lymphocytes, the signal pathway associated with MOR gene
      transcription remains to be better defined. As the phosphatidylinositol 3-kinase
      (PI3K)/AKT pathway can mediate diverse biological responses and is crucial for
      optimal immune responses and lymphocyte development, this study was undertaken to
      delineate the role of PI3K/AKT signaling in expression of the MOR gene in CEM
      x174 cells. The data show that morphine treatment enhanced the level of
      phosphorylated, rather than un-phosphorylated, PI3K and AKT, which were
      synchronously recruited to membrane. The levels of PTEN and p53 which are
      negative regulators of these signal molecules were reduced, and as a result, the
      interaction between PTEN and p53 was completely interrupted. With morphine
      treatment, the levels of both cytoplasmic and nuclear E2F1 which is the
      downstream effecter of AKT were elevated and the interaction of E2F1 with YY1,
      rather than Sp1, was also increased. Subsequently, E2F1 triggered the
      transcription of the MOR gene through its enhanced ability to bind the element in
      promoter region of the MOR gene. All responses to morphine were abolished by
      naloxone, which is an antagonist of MOR, or by LY294002, an inhibitor of PI3K,
      implying specific involvement of PI3K/AKT. These results strongly suggest that
      the PI3K/AKT pathway plays a critical role in the transfer of signal from
      morphine stimuli to the machinery by which MOR gene transcription is initiated.

PMID- 19765551
TI  - The impact of non-noxious heat on tactile information processing.
AB  - A significant number of studies that evaluated tactile-pain interactions employed
      heat to evoke nociceptive responses. However, relatively few studies have
      examined the effects of non-noxious thermal stimulation on tactile discriminative
      capacity. In this study, the impact that non-noxious heat had on three features
      of tactile information processing capacity was evaluated: vibrotactile threshold,
      amplitude discriminative capacity, and adaptation. It was found that warming the
      skin made a significant improvement on a subject's ability to detect a
      vibrotactile stimulus, and although the subjects' capacities for discriminating
      between two amplitudes of vibrotactile stimulation did not change with skin
      heating, the impact that adapting or conditioning stimulation normally had on
      amplitude discrimination capacity was significantly attenuated by the change in
      temperature. These results suggested that although the improvements in tactile
      sensitivity that were observed could have been a result of enhanced peripheral
      activity, the changes in measures that reflect a decrease in the sensitization to
      repetitive stimulation are most likely centrally mediated. The authors speculate
      that these centrally mediated changes could be a reflection of a change in the
      balance of cortical excitation and inhibition.

PMID- 19765552
TI  - Arithmetic procedural knowledge: a cortico-subcortical circuit.
AB  - The disturbances of arithmetic procedural knowledge form a heterogeneous picture,
      in which we can distinguish "memory" impairments and "monitoring" problems.
      Patients with "memory" disturbances reported in the literature present left
      parietal lesions, while "monitoring" impairments have been assumed to be due to
      frontal damage. Procedural knowledge has been less investigated in basal ganglia
      lesions, in which there has been no analysis of procedural impairments. The
      present study investigates and compares the patterns of acalculia in two
      patients, one with a left parietal lesion and the other with a left basal ganglia
      lesion. The patients were tested on a broad range of neuropsychological
      abilities, with the main focus on number processing and calculation. The results
      show many similarities between their deficits, with some difficulties in simple
      arithmetic, arithmetical rules and mental and written complex calculations. The
      errors made in complex mental and written calculations were due to memory-based
      procedural impairments in both patients. These findings, corroborated with other
      studies reported in the literature, suggest the existence of a fronto-parieto
      subcortical circuit responsible for arithmetic complex calculations and that
      procedural knowledge relies on a visuo-spatial sketchpad that contains a
      representation of each sub-step of the procedure.

PMID- 19765553
TI  - Expression pattern of NuIP gene in adult mouse brain.
AB  - We previously reported the identification of the Nurr1 interacting protein (NuIP)
      that was demonstrated to modulate the transcriptional activity of Nurr1, the
      orphan nuclear receptor required for midbrain dopaminergic neuron
      differentiation. NuIP was also cloned by others and referred to as a small G
      protein signaling modulators. The open reading frame of NuIP predicts a protein
      with an N-terminal RUN domain (RPIP8, UNC-14, and NESCA) and a C-terminal TBC
      domain (Tre-2, Bub2, and Cdc16) both of which are found in proteins of the GTPase
      activating protein (GAP) family, involved in the GTPase signaling pathway. To
      characterize the NuIP gene product, we developed a polyclonal antibody. Since
      NuIP gene is expressed most abundantly in adult and the level of expression
      during development is below the detection limit of immunohistochemistry, we now
      report the expression pattern of NuIP in adult mouse brain compared with the
      expression pattern of Nurr1 protein. Many regions co-expressed Nurr1 and NuIP
      including cortex, hippocampus, substantia nigra, and the cerebellum. However,
      there are also regions that exclusively express NuIP such as striatum, septum,
      globus pallidus, and the reticular thalamic nucleus. We also find that NuIP
      protein expresses mainly in NeuN-positive (neuronal nuclei) neurons but can be
      detected in GFAP-positive (glial fibrillary acidic protein) glial cells in
      hippocampus. Interestingly, NuIP is expressed in high levels in midbrain
      dopaminergic neurons including ventral tegmental area (VTA) and substantia nigra
      (SN) dopaminergic neurons but is not expressed or expressed in low levels in
      other dopaminergic neurons such as olfactory bulb and hypothalamus. Overall, the
      expression pattern of NuIP in adult mouse brain suggests that it may be involved
      in motor activity control in basal ganglia as well as higher central nervous
      system (CNS) functions such as cognition and memory in cortex and hippocampus.

PMID- 19765554
TI  - The role of parietal cortex during sustained visual spatial attention.
AB  - The control of spatial attention-shifting attention between visual field
      locations or sustaining attention to one location-involves the prefrontal cortex
      and parietal cortex. Within the parietal cortex, shifting attention has been
      linked to the superior parietal lobule; however, the neural substrates associated
      with sustained attention are still unknown. In the present fMRI study, we aimed
      to identify generalized control regions associated with sustained attention using
      two different protocols. The motion protocol alternated between periods of moving
      or stationary dots, and the flicker protocol alternated between periods of
      flickering or stationary checkerboards (each period lasted 14 s). During moving
      and flickering periods, the behavioral task alternated between sustained
      attention and perception. A region-of-interest analysis confirmed that the motion
      but not flicker protocol produced attention effects-greater activity associated
      with sustained attention than perception-in motion processing region MT+. A whole
      brain conjunction analysis identified regions commonly associated with sustained
      attention for both protocols, which included the right intraparietal sulcus (BA
      7/40), the right middle frontal gyrus (BA 9/46), the right superior temporal
      gyrus (BA 22), the right insula (BA 13), and the left cerebellum. Coupled with
      previous results, the present findings suggest a functional-anatomic organization
      of parietal cortex where shifts in attention are mediated by superior regions and
      sustained attention is mediated by more lateral regions.

PMID- 19765555
TI  - Effects of gestational stress: 2. Evaluation of male and female adult offspring.
AB  - Physical restraint applied during gestation is a commonly employed animal model
      of human pregnancy stress. The consequences of such a paradigm have been
      extensively investigated in adult male rats using a variety of physiological and
      behavioral measures. The behavioral repertoire of female offspring, however, has
      been largely ignored. The current study examines adult offspring-male and female
      Long Evans rats (55-90 days of age) and is a follow-up report to the consequences
      of maternal restraint (gestation days 10 through 19) in mother rats and their
      juvenile offspring. Physiological measures included weight and estrous cycle
      regularity. Elevated plus maze and emergence tests were used to measure anxiety,
      and the T-maze test, cognition. Data were analyzed via hierarchical linear
      modeling to account for the nesting of offspring within litters. Compared to same
      sex controls, males from stressed mothers displayed a progressive attenuated
      weight gain over experimental weeks while females from stressed mothers
      maintained a stable, lower weight throughout. Twenty-five percent of females in
      the stressed group and none in the control group displayed irregular cycles in
      the first week of testing; on subsequent weeks, this group discrepancy ranged
      from 1% to 11%. Subtle effects were observed in anxiety measures: an interaction
      between sex and stress group in the analysis of head dip behavior in the elevated
      plus maze and decreased emergence latencies in stress groups. Results demonstrate
      the importance of examining the effects of maternal stress in offspring of both
      sexes at various developmental stages.

PMID- 19765556
TI  - The cardiovascular response of normal rats to dual lesion of the subfornical
      organ and area postrema at rest and to chronic losartan.
AB  - The subfornical organ (SFO) and the area postrema (AP), two of the sensory
      circumventricular organs (CVO), are known to play a role in the chronic central
      control of blood pressure. In previous studies in which these regions were
      independently lesioned, the chronic hypotensive effects of the AT(1) receptor
      blocker losartan (10 mg/kg/day) were attenuated by ~15 mm Hg. In the present
      study, we sought to investigate the effect of concurrent lesion of both the SFO
      and the AP on the cardiovascular effects of chronic losartan infusion in order to
      test the hypothesis that a greater attenuation of the hypotensive effects of
      losartan would be observed in rats with dual lesions. To do so, arterial pressure
      and heart rate responses to 10-day infusion of losartan were compared in sham
      rats and those with dual lesions of the AP and SFO. Two important findings
      resulted from this study. First, dual lesion rats exhibited a sustained and
      significant decrease in resting blood pressure (83+/-1 mm Hg vs. 104+/-1 mm Hg,
      respectively) and heart rate (356+/-3 bpm vs. 398+/-6 bpm, respectively) compared
      to sham animals. Secondly, rats with concurrent lesion of both the AP and the SFO
      demonstrated a significantly attenuated response to losartan compared to sham
      animals but showed no greater attenuation of losartan's chronic hypotensive
      effects than animals with lesion of either the SFO or the AP (approximately 15 mm
      Hg). Although these results do not support the stated hypothesis, they do suggest
      redundancy and compensatory roles of the AP and SFO in basal cardiovascular
      control.

PMID- 19765558
TI  - Parasympathetic vasodilator fibers in rat digastric muscle.
AB  - The present study examined whether parasympathetic vasodilator fibers exist in
      rat jaw-opening muscles such as the digastric muscle. The mental nerve was
      stimulated to activate the parasympathetic vasodilator nerve in the digastric
      muscle. Electrical stimulation of the mental nerve elicited intensity- and
      frequency-dependent increases of blood flow in this muscle. These increases were
      markedly reduced by hexamethonium in dose- and time-dependent manners, but
      pretreatment with phentolamine or propranolol had no effect. Pretreatment with
      atropine also attenuated the increase in blood flow in digastric muscle. When
      retrograde fluorogold was injected into the digastric muscle, labeled neurons
      were observed in the otic ganglion only on the ipsilateral side, but not in the
      pterygopalatine ganglion of either side. These results indicate that
      parasympathetic vasodilator fibers originate from cell bodies in the otic
      ganglion in rat digastric muscle.

PMID- 19765557
TI  - The locus coeruleus: A key nucleus where stress and opioids intersect to mediate
      vulnerability to opiate abuse.
AB  - The interaction between the stress axis and endogenous opioid systems has gained
      substantial clinical attention as it is increasingly recognized that stress
      predisposes to opiate abuse. For example, stress has been implicated as a risk
      factor in vulnerability to the initiation and maintenance of opiate abuse and is
      thought to play an important role in relapse in subjects with a history of abuse.
      Numerous reports indicating that stress alters individual sensitivity to opiates
      suggest that prior stress can influence the pharmacodynamics of opiates that are
      used in clinical settings. Conversely, the effects of opiates on different
      components of the stress axis can impact on individual responsivity to stressors
      and potentially predispose individuals to stress-related psychiatric disorders.
      One site at which opiates and stress substrates may interact to have global
      effects on behavior is within the locus coeruleus (LC), the major brain
      norepinephrine (NE)-containing nucleus. This review summarizes our current
      knowledge regarding the anatomical and neurochemical afferent regulation of the
      LC. It then presents physiological studies demonstrating opposing interactions
      between opioids and stress-related neuropeptides in the LC and summarizes results
      showing that chronic morphine exposure sensitizes the LC-NE system to
      corticotropin releasing factor and stress. Finally, new evidence for novel
      presynaptic actions of kappa-opioids on LC afferents is provided that adds
      another dimension to our model of how this central NE system is co-regulated by
      opioids and stress-related peptides.

PMID- 19765559
TI  - T-box 3 is expressed in the adult mouse hypothalamus and medulla.
AB  - Using microarray analysis, in situ hybridization and immunocytochemistry, we
      found that the transcription factor TBX3 is produced in three discrete neuronal
      populations of the adult mouse brain, the arcuate nucleus (including in NPY but
      not dopaminergic neurons), the histaminergic tuberomammillary nucleus and in
      cholinergic neurons of the solitary tract nucleus. The immunoreactive protein had
      a nuclear location in these neurons, consistent with its function as a
      transcription factor. Although the function of tbx3 in these neurons is unknown,
      a review of the literature strongly suggests that these neuronal populations may
      be abnormal in Ulnar-Mammary syndrome patients with tbx3 mutations, explaining
      previously overlooked phenotypes in this syndrome, such as obesity, sexual
      dysfunction and possibly sleep abnormalities.

PMID- 19765560
TI  - Abnormal resting-state functional connectivity of posterior cingulate cortex in
      amnestic type mild cognitive impairment.
AB  - Amnestic type mild cognitive impairment (aMCI) refers to a transitional stage
      between normal aging and Alzheimer's disease (AD). Whilst posterior cingulate
      cortex (PCC) is believed to have a key role in a default network and be involved
      in the pathophysiology of AD, few studies have investigated whole-brain
      functional connectivity of PCC during resting state, or investigated the
      relationship between abnormal functional connectivity and disturbance in
      cognitive function in aMCI patients. Resting-state functional connectivity
      analysis was used to examine the temporal correlation between PCC and whole-brain
      regions in 30 aMCI patients and 26 well-matched controls. Further analysis
      involved evaluation of possible relationships between functional connectivity
      measures and cognitive function. Regions of decreased functional connectivity
      were identified in aMCI patients, most notably in temporal cortex, whilst
      significantly increased functional connectivity was mainly in frontal cortex. In
      addition, functional connectivity of PCC and temporal cortex was associated with
      the performance of neuropsychological tests in aMCI patients. This would be
      consonant with the recruitment of compensatory mechanisms and the process of
      offset functional impairments appearing as neuropathologic develops, and resting
      state connectivity disturbance of PCC-temporal cortex may be a central role in
      cognitive deficit in aMCI patients.

PMID- 19765561
TI  - Attentional processes and blood lactate levels.
AB  - The accumulation of lactate in the blood after a high-intensity exercise is
      associated to an increase of lactate extractions by the brain. However, no
      information has been provided about the influences of blood lactate on cognitive
      performances and, in particular, on attention. The present study was carried out
      to examine the association of high blood lactate levels, induced with a maximal
      cycling, with two different attentional tasks. The study was carried out on 17
      male sprinters who performed exhaustive exercise. Before the exercise, as well as
      5 and 10 min after the exhaustion, blood lactate was measured and intensity as
      well as selectivity of attention of each subject were evaluated. Same
      measurements were performed on 6 out of 17 subjects who accepted to receive an
      intravenous infusion of a lactate solution. In both experimental conditions, an
      inverse relation between scores in both aspects of attention and blood lactate
      levels was observed.

PMID- 19765562
TI  - Characteristic response of astrocytes to plasminogen/plasmin to upregulate
      transforming growth factor beta 3 (TGFbeta3) production/secretion through
      proteinase-activated receptor-1 (PAR-1) and the downstream phosphatidylinositol 3
      kinase (PI3K)-Akt/PKB signaling cascade.
AB  - The effects of microglia-derived plasminogen (PLGn) on the neurotrophic role of
      astrocytes were investigated in vitro. The treatment of astrocytes with rat PLGn
      led to a significant increase in transforming growth factor beta3 (TGFbeta3) in
      the conditioned medium (CM). This response of astrocytes to PLGn was
      characteristic and different from that to other stimulators, including
      lipopolysaccharide, phorbol-12-myristate-13-acetate, interferon-gamma, and ATP.
      In surveying the signaling molecules that respond to PLGn in astrocytes, we found
      that Akt/PKB phosphorylation is promoted. The pretreatment of astrocytes with an
      Akt inhibitor prior to PLGn stimulation resulted in a significant decrease in
      TGFbeta3 amounts in the CM, suggesting an association of Akt with TGFbeta3
      production/secretion. Further survey revealed that phosphatidylinositol 3 kinase
      (PI3K) is closely associated with TGFbeta3 production/secretion in astrocytes. In
      fact, PI3K inhibitor clearly depressed the phosphorylation of Akt, indicating
      that PI3K is localized upstream of Akt. Moreover, the effects of PLGn to increase
      TGFbeta3 were depressed by pretreatment with a proteinase-activated receptor-1
      (PAR-1) inhibitor. Plasmin could mimic the PLGn effects to upregulate TGFbeta3,
      and the plasmin effects were suppressed by pretreatment with the PAR-1 inhibitor,
      suggesting the association of PLGn/plasmin effects with PAR-1. In addition, Akt
      phosphorylation caused by plasmin was inhibited in the presence of PAR-1
      inhibitor. We have therefore demonstrated that PLGn/plasmin, probably plasmin,
      facilitates the production/secretion of TGFbeta3 in astrocytes through both PAR-1
      and the subsequent signaling cascade including PI3K and Akt.

PMID- 19765564
TI  - Temporal assessment of histone H3 phospho-acetylation and casein kinase 2
      activation in dentate gyrus from ischemic rats.
AB  - Hippocampal dentate gyrus possesses an exceptional capacity of adaptation to
      ischemic insults. Recently, using a transient global ischemic model in the adult
      rat, we identified a neuroprotective signalling cascade in the dentate gyrus
      involving calcium/calmodulin-dependent protein kinase IV (CaMKIV), cyclic AMP
      response element (CRE)-binding protein (CREB) and brain-derived neurotrophic
      factor (BDNF), a major regulator of survival. We have shown that
      intracerebroventricular injections of anti-BDNF and anti-CREB are sufficient to
      cause substantial tissular damages and apoptotic deaths in late periods (48-72 h)
      after ischemia. Herein, we provide immunohistochemical and biochemical evidence
      that antibody-induced impairment of the protective CaMKIV/CREB/BDNF pathway
      induces an apparent duality of response in the dentate gyrus. The experimental
      protocol is performed as follows: (a) rats are anesthetized and vertebral
      arteries are occluded by electrocauterization; (b) on the following day,
      transient global ischemia is produced by occlusion of carotid arteries for 25
      min; (c) finally, rats are infused with the pharmacologic agents into the left
      cerebral ventricle and then perfusion-fixed at different time points after
      ischemia for immunohistochemical and immunoblotting analyses. After infusion with
      anti-CaMKIV, phosphorylation of mitogen-activated protein kinases (MAPK) MKK3,
      MKK6 and p38 and phospho-acetylation of histone H3 occur at 6 h after ischemia
      without presence of any caspase-9 activation and cellular injuries. In contrast,
      infusion of anti-BDNF or anti-CREB surprisingly results in a remarkable
      stimulation of casein kinase 2 (CK2) and caspase-9 activities at 48-72 h post
      insult. This is accompanied by the disappearance of phosphorylation of MKK(3/6)
      and p38 and phospho-acetylation of histone H3. These results suggest that: (1)
      activation of a MKK(3/6)/p38/H3 cascade at early periods post-ischemia may be
      capable of causing a short transient protective effect in the dentate gyrus; (2)
      CK2 might be implicated in inhibition of activity of molecules such as MKK(3/6),
      p38 and deacetylases at late periods post-insult, thereby promoting injuries and
      cell deaths in the dentate cell layer.

PMID- 19765563
TI  - Marine compound Xyloketal B protects PC12 cells against OGD-induced cell damage.
AB  - Xyloketal B is a novel marine compound with unique chemical structure isolated
      from mangrove fungus Xylaria sp. (no. 2508). Recently, we have demonstrated that
      Xyloketal B is an antioxidant and can protect against oxidized low density
      lipoprotein (LDL)-induced cell injury. In the present study, we investigated
      whether Xyloketal B can protect against ischemia-induced cell injury in an in
      vitro oxygen glucose deprivation (OGD) model of ischemic stroke in PC12 cells. We
      found that Xyloketal B could directly scavenge 1,1-diphenyl-2-picrylhydrazyl
      (DPPH) free radical and protect PC12 cells against OGD insult. Furthermore,
      Xyloketal B alleviated OGD-induced mitochondria superoxide, mitochondria
      fragmentation and GTPase dynamin-related protein 1 (Drp1) overexpression as well
      as reduction of mitochondrial membrane potential. All together, the present study
      demonstrates that Xyloketal B protects PC12 cells against OGD-induced cell injury
      and that the anti-oxidative property and protective action on mitochondria may
      account for its neuroprotective actions.

PMID- 19765565
TI  - Temporal course and the electrophysiological correlates of hypothesis testing as
      revealed in a modified category induction task.
AB  - The present study used a modified category induction task to examine the brain
      activation that occurs when a person receives the result of hypothesis testing
      (HT). Participants were provided with a number of different batteries and were
      asked to learn what kinds of batteries were charged. Within each trial, two
      batteries were sequentially displayed, and a preliminary hypothesis could be
      formed based on the perceptual comparison. A third battery was then displayed
      that served to strengthen, reject or maintain the preliminary hypothesis.
      Finally, a probe appeared for three seconds or terminated with a response. The
      behavioral results revealed that the highest accuracies and the quickest
      responses occurred for the Strengthen condition compared with the two other
      conditions. The electrophysiological results, which were time-locked to the third
      batteries, showed that (1) the posterior sites were selectively activated in
      response to the critical property of a hypothesis; (2) during the time window of
      P300, the central areas were activated, reflecting the process of matching the
      test stimulus to the representation of a hypothesis; and (3) during the late time
      window, an enhanced hypothesis-rejection-related potential was found over the
      fronto-central sites, which suggested that the preliminary hypothesis had been
      evaluated and the cognitive context had been updated.

PMID- 19765566
TI  - Curcumin is protective against phenytoin-induced cognitive impairment and
      oxidative stress in rats.
AB  - The present study investigates the effect of chronic curcumin administration on
      phenytoin-induced cognitive impairment and oxidative stress in rats. Male Wistar
      rats were administered drugs/vehicle for 21 days. Learning and memory was
      evaluated using the passive avoidance paradigm and the elevated plus maze. On day
      21, serum phenytoin concentrations and whole brain malondialdehyde (MDA) and
      glutathione (GSH) levels were estimated. Phenytoin (75 mg/kg, i.p.) produced
      significant deficits in learning/memory as indicated by the significant increase
      in retention transfer latency in elevated plus maze test and a significant
      decrease in retention latency in the passive avoidance paradigm. Chronic
      administration of phenytoin also produced significant elevations in brain MDA and
      reduction of brain GSH levels. Curcumin (100, 200 and 300 mg/kg, orally), when
      administered with phenytoin, significantly prevented phenytoin-induced cognitive
      impairment and oxidative stress in a dose-dependent manner. There were no
      significant differences in the serum levels of phenytoin in any of the treatment
      groups. This study demonstrates that curcumin is effective in preventing
      phenytoin-induced cognitive impairment and oxidative stress in rats without
      altering the serum phenytoin levels. This suggests the potential of adjuvant
      curcumin therapy in ameliorating cognitive impairment caused by chronic phenytoin
      therapy.

PMID- 19765567
TI  - Event-related potentials for simple arithmetic in Arabic digits and Chinese
      number words: a study of the mental representation of arithmetic facts through
      notation and operation effects.
AB  - To test whether the retrieval of arithmetic facts is independent of numerical
      notations, this study investigated the event-related potentials elicited by
      single-digit addition and multiplication problems in Arabic digits and Chinese
      number words. The results showed that, in comparison with addition,
      multiplication elicited a greater N300-like component at the left anterior
      electrodes and greater late positive potentials at the right posterior
      electrodes, regardless of numerical notations. The operation effects lasted from
      250 to 900 ms for Arabic digits, but from 250 to 1400 ms for Chinese number words
      when participants were asked to respond only to false arithmetic equations
      (experiment one), and lasted from 350 to 1400 ms for Arabic digits and Chinese
      number words when participants were asked to respond to both true and false
      arithmetic equations (experiment two). The consistency in the operation effects
      in ERPs (i.e., a dissociation of brain organization for different arithmetic
      operations) for different number notations suggests that mental representation
      and retrieval of arithmetic facts may be relatively independent of numerical
      notations.

PMID- 19765568
TI  - Detection of early neuron degeneration and accompanying glial responses in the
      visual pathway in a rat model of acute intraocular hypertension.
AB  - Transsynaptic degeneration has been implicated in patients with primary open
      angle glaucoma (POAG) and animal models of chronic intraocular hypertension.
      Whether the sustained intraocular pressure (IOP) elevation is necessary for the
      induction of transsynaptic changes in the brain remains unclear. The aim of this
      study is to characterize the effects of acute and transient intraocular
      hypertension on the visual pathway of rats. Acute intraocular hypertension was
      induced in the right eye by anterior chamber perfusion. At 1 day, 3 days, 1 week,
      2 weeks and 4 weeks after the operation, neuronal degeneration and glial
      responses in the retina, dorsal lateral geniculate nucleus (dLGN) and superior
      colliculus (SC) were assessed using Nissl staining and immunohistochemistry.
      TUNEL staining was also performed to detect the neuronal apoptosis in the brain.
      At the first day after the operation, no obvious neuronal changes were detected
      in the retina or the brain. At 3 days, 46% of the retinal ganglion cells (RGCs)
      were lost. Atrophy of the contralateral optic tract was also observed. Meanwhile,
      the cross-sectional area of neurons in the contralateral dLGN and SC was
      decreased, while cell density in the same regions was increased. Glial activation
      in the retina occurred much earlier than the RGC loss. Co-expression of glial
      fibrillary acid protein (GFAP) and glutamine synthetase (GS) was observed in the
      end-feet and processes of Muller cells at 1 day after the operation. GFAP
      immunoreactivity was remarkably increased in the contralateral dLGN and SC at 3
      days. It also showed a good co-localization with GS. All of aforementioned
      changes gradually progressed and persisted for the whole observation period. No
      TUNEL-positive cells were detected in the dLGN and SC at any post-operative time
      point. Taken together, these results illustrate that acute and transient
      intraocular hypertension is able to induce early onset and long-lasting
      neurodegenerative changes and the accompanying glial activation in the visual
      pathway. Brain changes may occur in parallel with the RGC loss. Reactive glial
      cells in the brain may participate in the clearance of aberrantly released
      glutamate and may serve as a sensitive marker of neuronal injury. Neuroprotection
      of the entire visual pathway and glia-target therapies may bring new insights
      into the glaucoma treatment.

PMID- 19765569
TI  - Herb-drug interaction of silymarin or silibinin on the pharmacokinetics of
      trazodone in rats.
AB  - Silymarin, one of the most popular herbal medicines, has been widely used for its
      hepatoprotective effects. This study investigates the effects of repeated dose of
      silymarin and its major ingredient, silibinin, on the pharmacokinetics of the
      antidepressant trazodone. Treatment groups included vehicle control group,
      concomitant silymarin at 1.0g/kg dose, and four 7-day repeated dose induction
      groups of 0.5 and 1.0g/kg silymarin and 0.175 and 0.35g/kg silibinin.
      Microdialysis coupled with high performance liquid chromatography (HPLC) was used
      to simultaneously monitor blood and bile concentrations of trazodone in the rats.
      Results indicate that pretreatment with an extremely high dose of 1.0g/kg
      silymarin significantly decreases trazodone's area under concentration curve
      (AUC), distribution half-life (t(1/2,alpha)), elimination half-life
      (t(1/2,beta)), and mean residence time (MRT). In conclusion, the present study
      finds no marked effects of silymarin and silibinin on the pharmacokinetics of
      trazodone under normal daily doses and the relative safety of taking the herb
      with trazodone.

PMID- 19765570
TI  - The Galpha4 G protein subunit interacts with the MAP kinase ERK2 using a D-motif
      that regulates developmental morphogenesis in Dictyostelium.
AB  - G protein Galpha subunits contribute to the specificity of different signal
      transduction pathways in Dictyostelium discoideum but Galpha subunit-effector
      interactions have not been previously identified. The requirement of the
      Dictyostelium Galpha4 subunit for MAP kinase (MAPK) activation and the
      identification of a putative MAPK docking site (D-motif) in this subunit
      suggested a possible interaction between the Galpha4 subunit and MAPKs. In vivo
      association of the Galpha4 subunit and ERK2 was demonstrated by pull-down and co
      immunoprecipitation assays. Alteration of the D-motif reduced Galpha4 subunit
      ERK2 interactions but only slightly altered MAPK activation in response to
      folate. Expression of the Galpha4 subunit with the altered D-motif in galpha4(
      )cells allowed for slug formation but not the morphogenesis associated with
      culmination. Expression of this mutant Galpha4 subunit was sufficient to rescue
      chemotactic movement to folate. Alteration of the D-motif also reduced the
      aggregation defect associated with constitutively active Galpha4 subunits. These
      results suggest Galpha4 subunit-MAPK interactions are necessary for developmental
      morphogenesis but not for chemotaxis to folate.

PMID- 19765571
TI  - Blocking hedgehog signaling after ablation of the dorsal neural tube allows
      regeneration of the cardiac neural crest and rescue of outflow tract septation.
AB  - Cardiac neural crest cells (CNCC) migrate into the caudal pharynx and arterial
      pole of the heart to form the outflow septum. Ablation of the CNCC results in
      arterial pole malalignment and failure of outflow septation, resulting in a
      common trunk overriding the right ventricle. Unlike preotic cranial crest, the
      postotic CNCC do not normally regenerate. We applied the hedgehog signaling
      inhibitor, cyclopamine (Cyc), to chick embryos after CNCC ablation and found
      normal heart development at day 9 suggesting that the CNCC population was
      reconstituted. We ablated the CNCC, and labeled the remaining neural tube with
      DiI/CSRE and applied cyclopamine. Cells migrated from the neural tube in the CNCC
      ablated, cyclopamine-treated embryos but not in untreated CNCC-ablated embryos.
      The newly generated cells followed the CNCC migration pathways, expressed neural
      crest markers and supported normal heart development. Finally, we tested whether
      reducing hedgehog signaling caused redeployment of the dorsal-ventral axis of the
      injured neural tube, allowing generation of new neural crest-like cells. The
      dorsal neural tube marker, Pax7, was maintained 12 h after CNCC ablation with Cyc
      treatment but not in the CNCC-ablated alone. This disruption of dorsal-ventral
      neural patterning permits a new wave of migratory cardiac neural crest-like
      cells.

PMID- 19765572
TI  - Neural ectoderm-secreted FGF initiates the expression of Nkx2.5 in cardiac
      progenitors via a p38 MAPK/CREB pathway.
AB  - Vertebrate heart development is derived from paired primordia of anterior
      dorsolateral mesoderm expressing Nkx2.5 and GATA4 transcription factors. Yet
      growth factors and intracellular pathways specifying heart precursor gene
      expression are poorly understood. In the present work, we investigated the
      signaling events initiating Nkx2.5 expression in Xenopus laevis. We describe here
      that fibroblast growth factor (FGF) initiates the expression of Nkx2.5 without
      affecting GATA4. At gastrula, FGF3 is expressed in anterior neural ectoderm, and
      results presented here indicate that this tissue is involved in the induction of
      Nkx2.5 expression in neighboring lateral tissues. Further studies indicate that
      the intracellular p38 MAPK and the CREB transcription factor function downstream
      of FGF to initiate Nkx2.5 expression. Activation of the p38 MAPK pathway and of
      the CREB protein is both necessary and sufficient for the initial expression of
      Nkx2.5. Therefore, we would like to suggest that FGF expressed in anterior neural
      ectoderm is a major inducer of Nkx2.5 expression in neighboring cells. In these
      cells, FGF activates an intracellular p38 MAPK signaling pathway and its
      downstream target, the CREB transcription factor, all participating in the
      expression of Nkx2.5 in cardiac progenitors.

PMID- 19765573
TI  - alpha-Linolenic acid protects renal cells against palmitic acid lipotoxicity via
      inhibition of endoplasmic reticulum stress.
AB  - Unsaturated fatty acids may counteract the lipotoxicity associated with saturated
      fatty acids. Palmitic acid induced endoplasmic reticulum (ER) stress and caused
      apoptotic and necrotic cell death in the renal proximal tubular cell line, NRK
      52E. We investigated whether alpha-linolenic acid, an unsaturated fatty acid,
      protected against ER stress and cell death induced by palmitic acid or by other
      non-nutrient ER stress generators. Incubation of NRK-52E cells for 24h with
      palmitic acid produced a significant increase in apoptosis and necrosis. Palmitic
      acid also increased levels of three indicators of ER stress - the phosphorylated
      form of the eukaryotic initiation factor 2alpha (eIF2alpha), C/EBP homologous
      protein (CHOP), and glucose regulated protein 78 (GRP78). alpha-Linolenic acid
      dramatically reduced cell death and levels of all three indicators of ER stress
      brought about by palmitic acid. Tunicamycin, which induces ER stress by
      glycosylation of proteins, produced similar effects to those obtained using
      palmitic acid; its effects were partially reversed by alpha-linolenic acid.
      Salubrinal (a phosphatase inhibitor) causes increased levels of the
      phosphorylated form of eIF2alpha - this effect was partially reversed by alpha
      linolenic acid. Palmitoleate, a monosaturated fatty acid, had similar effects to
      those of alpha-linolenic acid. These results suggest that part of the mechanism
      of protection of the kidney by unsaturated fatty acids is through inhibition of
      ER stress, eIF2alpha phosphorylation and consequential reduction of CHOP protein
      expression and apoptotic renal cell death.

PMID- 19765574
TI  - Isoflurane and sevoflurane dose-dependently impair hippocampal long-term
      potentiation.
AB  - Isoflurane and sevoflurane are commonly used volatile anaesthetics. Although
      acting via similar cellular mechanisms, the effect of different volatile
      anaesthetics on synaptic plasticity might differ. In the present study, using
      acute murine brain slice preparations, we compared the effects of isoflurane and
      sevoflurane on synaptic transmission and synaptic plasticity (long-term
      potentiation, LTP) in the CA1 stratum radiatum of the hippocampus. Isoflurane and
      sevoflurane dose-dependently diminished excitatory postsynaptic field potentials.
      In the presence of isoflurane (sevoflurane) at concentrations of 0.19, 0.28 and
      0.37mM (0.11, 0.21 and 0.42mM), which correspond to 0.7-, 1.0- and 1.4-fold (0.3
      , 0.6- and 1.1-fold) minimum alveolar concentration (MAC), high frequency
      stimulation reliably induced LTP. When isoflurane (sevoflurane) was applied at
      concentrations of 0.56 and 0.74mM (0.63 and 0.84mM), which equal 2.1- and 2.7
      fold (1.7- and 2.2-fold) MAC, LTP was blocked. Our results indicate, that both
      anaesthetics influence synaptic strength to a similar degree, with only high
      concentrations blocking hippocampal CA1 stratum radiatum long-term potentiation.

PMID- 19765575
TI  - Comparison of the mGlu(5) receptor positive allosteric modulator ADX47273 and the
      mGlu(2/3) receptor agonist LY354740 in tests for antipsychotic-like activity.
AB  - Recently, it has been proposed that activation of either metabotropic glutamate
      receptors e.g. mGlu(5) by positive allosteric modulators or stimulation of
      mGluR(2/3) receptors by agonists may offer new strategy in schizophrenia
      treatment. The aim of the present study was to compare the effect of mGlu(5)
      receptor positive allosteric modulator, ADX47273 (S-(4-Fluoro-phenyl)-{3-[3-(4
      fluoro-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-methanone), mGluR(2/3)
      agonist, LY354740 ((1S,2S,5R,6S)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylate
      monohydrate) and selected neuroleptics in animal models for positive
      schizophrenia symptoms. ADX47273 (3 and 10mg/kgi.p.), the typical antipsychotic
      haloperidol (0.1 and 0.2mg/kgi.p.), the atypical antipsychotics aripiprazole
      (1.25-5mg/kgi.p.) and olanzapine (2.5 and 5mg/kgi.p.) all reduced amphetamine
      induced hyperlocomotion in Sprague-Dawley rats, unlike the mGlu(2/3) receptor
      agonist LY354740 (1-10mg/kgi.p.). Interestingly, haloperidol (0.1 and
      0.2mg/kgi.p.), aripiprazole (1.25-5mg/kgi.p.) and olanzapine (1.25-5mg/kgi.p.),
      but not ADX47273 (1-10mg/kgi.p.), all reduced spontaneous locomotion and rearings
      at doses effective against amphetamine-induced hyperlocomotion. This indicates
      that the effect of ADX47273 in combination with amphetamine may be specific, and
      also suggests a lack of sedative side effects. Moreover, ADX47273 (30mg/kgi.p.),
      haloperidol (0.1 and 0.2mg/kgi.p.) and aripiprazole (5 and 10mg/kgi.p.) reversed
      apomorphine (0.5mg/kgs.c.)-induced deficits of prepulse inhibition, whereas
      neither LY354740 (1-10mg/kgi.p.) nor olanzapine (1.25-5mg/kgi.p.) produced this
      effect. Lack of effect of olanzapine was unexpected and at present no convincing
      explanation can be provided. In conclusion, in selected rodent models for
      positive schizophrenia symptoms, ADX47273 showed better efficacy than LY354740.

PMID- 19765576
TI  - Reduced spatial learning in mice treated with NVP-AAM077 through down-regulating
      neurogenesis.
AB  - NR2A-containing N-methyl-D-aspartate (NMDA) receptors have important roles in
      influencing the long-term potentiation and spatial memory. Here using Morris
      water maze, we found that inhibition of NR2A-containing NMDA receptors by [(R)
      [(S)-1-(4-bromophenyl)-ethylamino]-(2, 3-dioxo-1,2,3,4-tetrahydroquinoxalin-5-yl)
      methyl]-phosphonic acid (NVP-AAM077) hindered the formation of spatial memory. An
      increasing number of reports suggest that adult hippocampal neurogenesis is
      involved in hippocampal-mediated learning. To explore the possible mechanisms
      understanding the reduced spatial memory by NVP-AAM077, we investigated the
      effects of NVP-AAM077 on neurogenesis. We found that NVP-AAM077 inhibited
      progenitor cells proliferation in the subventricular zone and dentate gyrus and
      reduced the survival of newborn cells in the dentate gyrus in the adult mice. In
      null mutant mice lacking neuronal nitric oxide synthase (nNOS) gene (nNOS(-/-)),
      the effects of NVP-AAM077 on neurogenesis disappeared. In addition, NVP-AAM077
      increased nNOS enzymatic activity. Our findings suggest that NVP-AAM077 reduced
      spatial learning through down-regulating neurogenesis in the adult hippocampus.

PMID- 19765577
TI  - Controversial action of positive modulator of subtype 7 of metabotropic glutamate
      receptors AMN082 on cortical epileptic afterdischarges in immature rats.
AB  - Some age-dependent epilepsies of infancy and childhood cannot be sufficiently
      treated with contemporaneous antiepileptics, therefore search for new mechanisms
      and new drugs active in pediatric patients is necessary. Possible anticonvulsant
      action of AMN082 (N,N'-dibenzhydryl-ethane-1,2-diamine dihydrochloride), a
      positive allosteric modulator of metabotropic glutamate receptor subtype 7, was
      examined in a model of epileptic afterdischarges elicited in three age groups of
      immature rats (12, 18 and 25days old) by electrical stimulation of sensorimotor
      cortex. AMN082 did not exhibit an anticonvulsant action against spike-and-wave
      type of afterdischarges generated in the thalamocortical system; on the contrary,
      moderate proconvulsant action was found in 12- and 18-day-old rats (more marked
      prolongation of afterdischarges with repeated stimulations). On the other hand,
      AMN082 significantly shortened the second type of afterdischarges reflecting
      spread of epileptic activity into limbic system frequently recorded in 25-day-old
      rats. These contradictory results mean that AMN082 will not be a broad-spectrum
      anticonvulsant but it might be useful as a seizure-specific antiepileptic drug.

PMID- 19765578
TI  - Anti-inflammatory action of mollugin and its synthetic derivatives in HT-29 human
      colonic epithelial cells is mediated through inhibition of NF-kappaB activation.
AB  - Mollugin is the active compound of Rubia cordifolia, which has been used as a
      traditional Chinese medicine for the treatment of various inflammatory diseases
      including arthritis and uteritis. In the present study, we investigated for the
      first time the inhibitory effects and the mechanisms of action of mollugin (M1)
      and its synthetic derivatives (M2-M4) on tumor necrosis factor (TNF)-alpha
      induced inflammatory responses in HT-29 human colon epithelial cells. Treatment
      with M1 and its derivatives M2-M4 significantly inhibited TNF-alpha-induced
      attachment of U937 monocytic cells to HT-29 cells, which mimics the initial phase
      of colon inflammation. TNF-alpha-induced mRNA induction of the chemokines,
      monocyte chemoattractant protein (MCP)-1 and interleukin (IL)-8, and the
      intercellular cell adhesion molecule (ICAM)-1, which are involved in adhesion
      between leukocytes and epithelial cells, was suppressed by M1-M4, and M1 was the
      most efficacious. In addition, M1-M4 significantly suppressed TNF-alpha-induced
      NF-kappaB transcriptional activity. Such NF-kappaB inhibitory activity of M1-M4
      (20 microM) correlated with their ability to suppress TNF-alpha-induced chemokine
      expression and U937 monocytic cell adhesion to HT-29 colonic epithelial cells.
      Treatment of HT-29 cells with M1 and PDTC, a NF-kappaB inhibitor, synergistically
      suppressed both TNF-alpha-induced NF-kappaB activation and monocytic cell
      adhesion to HT-29 cells. These results suggest that M1-M4 inhibit TNF-alpha
      induced expression of inflammatory molecules via NF-kappaB, and that M1, a potent
      NF-kappaB inhibitor, may be a valuable new drug candidate for the treatment of
      colon inflammation.

PMID- 19765579
TI  - Inhibition of DPP-4 with sitagliptin improves glycemic control and restores islet
      cell mass and function in a rodent model of type 2 diabetes.
AB  - Inhibition of dipeptidyl peptidase-4 (DPP-4) activity has been shown to improve
      glycemic control in patients with type 2 diabetes by prolonging and potentiating
      the actions of incretin hormones. This study is designed to determine the effects
      of the DPP-4 inhibitor sitagliptin on improving islet function in a mouse model
      of insulin resistance and insulin secretion defects. ICR mice were pre-treated
      with high fat diet and a low dose of streptozotocin to induce insulin resistance
      and impaired insulin secretion, respectively. Diabetic mice were treated with
      sitagliptin or the sulfonylurea agent glipizide as admixture to high fat diet for
      ten weeks. Sustained reduction of blood glucose, HbA(1c), circulating glucagon
      and improvement in oral glucose tolerance were observed in mice treated with
      sitagliptin. In contrast, glipizide improved glycemic control only during the
      early weeks and to a lesser degree compared to sitagliptin, and had no effect on
      circulating glucagon levels or glucose tolerance. The improvement in glycemic
      control in sitagliptin-treated mice was associated with a significant increase in
      glucose-dependent insulin secretion in both perfused pancreas and isolated
      islets. Importantly, in contrast to the lack of effect by glipizide, sitagliptin
      significantly restored beta and alpha cell mass as well as alpha/beta cell ratio.
      These data indicate that DPP-4 inhibition by sitagliptin provided better overall
      improvement of glycemic control compared to glipizide in the high fat
      diet/streptozotocin induced diabetic mouse model. The ability of sitagliptin to
      enhance islet cell function may offer insight into the potential for disease
      modification.

PMID- 19765580
TI  - Neuroprotective effects of the new diterpene, CBNU06 against beta-amyloid-induced
      toxicity through the inhibition of NF-kappaB signaling pathway in PC12 cells.
AB  - Alzheimer's disease is the most common form of dementia, causing progressive
      cognitive dysfunction, particularly memory loss. Recently, modulation of beta
      amyloid (Abeta) toxicity, one of the major potential causes of Alzheimer's
      disease, has emerged as a possible therapeutic approach to control the onset of
      Alzheimer's disease. In this study, we investigated the neuroprotective effects
      and possible mechanisms by which 19-hydroxy-1alpha,6-diacetoxy-6,7-seco-ent-kaur
      16-en-15-one-7,20-olide (named as CBNU06), a new diterpene isolated from Isodon
      japonicus, acts against Abeta-induced toxicity in PC12 cells. Pretreatment with
      CBNU06 (20 microg/ml) prior to Abeta(25)(-35) (25 microM) significantly increased
      the viability of PC12 cells in a dose-dependent manner when examined by Hoechst
      staining, MTT assay and Trypan blue exclusion assay. This protective effect was
      accompanied by the decrease in translocation of NF-kappaB p50 and p65 from the
      cytoplasm to the nucleus, and followed by the decrease in cyclooxygenase-2 (COX
      2) levels. In addition, pretreatment with CBNU06 significantly reversed the
      effect of Abeta on Bax and Bcl-2. Taken together, these results suggest that
      CBNU06 protected PC12 cells against Abeta-induced neurotoxicity through the
      inhibition of the NF-kappaB signaling pathways. Therefore, CBNU06 has the
      possible beneficial effects in Alzheimer's disease by attenuating Abeta-induced
      toxicity.

PMID- 19765581
TI  - Metformin primarily decreases plasma glucose not by gluconeogenesis suppression
      but by activating glucose utilization in a non-obese type 2 diabetes Goto
      Kakizaki rats.
AB  - Metformin is an anti-diabetic agent that has been reported to decrease plasma
      glucose by multiple mechanisms, such as decreasing hepatic glucose production and
      activating peripheral glucose utilization. In order to elucidate the primary
      glucose-lowering mechanism of metformin, the present study focused on a
      comparison of the acute effect between metformin and CS-917 as a direct
      gluconeogenesis inhibitor. We examined the effect of metformin and CS-917 on
      glucose turnover in intravenous glucose-loaded Goto-Kakizaki (GK) rats, and on
      gluconeogenesis and glucose utilization in rat hepatocytes. Moreover, the glucose
      lowering effect of metformin and CS-917 was compared in a fed and a fasted state
      in GK rats. In intravenous glucose-loaded GK rats, metformin and CS-917 lowered
      plasma glucose by increasing the glucose disappearance rate and by decreasing the
      glucose appearance rate, respectively. In rat hepatocytes, CS-917 but not
      metformin suppressed gluconeogenesis (IC(50)=0.136microM). Instead, metformin
      dose-dependently increased glucose uptake and the following lactate production at
      30 to 100microM. Metformin decreased plasma glucose more in a fed state than in a
      fasted state in GK rats. CS-917, however, decreased plasma glucose more in a
      fasted state. These results confirm that metformin primarily decreases plasma
      glucose not by gluconeogenesis inhibition but by activating glucose utilization
      in GK rats. Moreover, metformin and CS-917 have different glucose-lowering
      effects depending on the nutrient state, which may be related to differences in
      their mechanisms of action. Such differences in action may have implications for
      metformin and CS-917 in the treatment of type 2 diabetes patients.

PMID- 19765582
TI  - Promising multifunctional anti-Alzheimer's dimer bis(7)-Cognitin acting as an
      activator of protein kinase C regulates activities of alpha-secretase and BACE-1
      concurrently.
AB  - We have recently demonstrated that bis(7)-Cognitin, a promising multifunctional
      anti-Alzheimer's dimer, can remarkably reduce the generation of amyloid beta
      peptide (Abeta) by inhibiting beta-secretase (BACE-1) and activating alpha
      secretase activity. In this study, the mechanism(s) underlying bis(7)-Cognitin's
      regulation of the activity of these two proteases was further investigated. In
      N2a cells stably expressing human amyloid precursor protein with the Swedish
      mutation (APPswe), the reduction in Abeta production induced by 1microM bis(7)
      Cognitin was not altered by the co-pretreatment of muscarinic and nicotinic
      cholinergic receptor antagonists, indicating that the regulation of APP
      processing by this dimer is independent of cholinergic transmission. Furthermore,
      bis(7)-Cognitin (0.1-3microM) significantly increased protein kinase C (PKC)
      activity in cells and in vitro in a concentration-dependent manner.
      Administration of a PKC activator, phorbol 12-myristate 13-acetate (PMA),
      concentration-dependently increased the alpha-secretase cleavage products, and
      reduced the BACE-1 cleavage products. In addition, the inhibition of PKC
      prevented PMA- or bis(7)-Cognitin-induced alterations in alpha-secretase and BACE
      1 activities, eliminating reductions in Abeta production seen with PMA or the
      dimer. These results strongly suggest that bis(7)-Cognitin may reduce the
      biosynthesis of Abeta by inhibiting BACE-1 and activating alpha-secretase
      concurrently through the direct activation of PKC. Combined with previous
      findings of direct inhibition of AChE and BACE-1 by this dimer, this work
      indicates that strategy may have potential to provide new insights into designing
      novel drugs that target multiple steps of aberrant APP processing to treat
      Alzheimer's disease.

PMID- 19765583
TI  - Renoprotective effects of gamma-aminobutyric acid on ischemia/reperfusion-induced
      renal injury in rats.
AB  - Enhanced renal sympathetic nerve activity during ischemic period and the renal
      venous norepinephrine overflow after reperfusion play important roles in the
      development of ischemic acute kidney injury. We investigated the effect of gamma
      aminobutyric acid (GABA), an inhibitory neurotransmitter mainly in the central
      nervous system, on ischemia/reperfusion-induced acute kidney injury in
      anesthetized rats. Ischemic acute kidney injury was induced by clamping the left
      renal artery and vein for 45min followed by reperfusion 2weeks after the
      contralateral nephrectomy. Intravenous injection of GABA (10 and 50micromol/kg)
      to ischemic acute kidney injury rats dose-dependently suppressed the enhanced
      renal sympathetic nerve activity during the renal ischemia, the renal venous
      norepinephrine overflow after reperfusion and attenuated the ischemia/reperfusion
      induced renal dysfunction with histological damage. Intravenous injection of
      CGP52432 (0.1micromol/kg), a selective GABA(B) receptor antagonist, eliminated
      the preventive effect by GABA (50micromol/kg) on ischemic acute kidney injury. In
      contrast, intravenous injection of baclofen (1micromol/kg), a selective GABA(B)
      receptor agonist, attenuated the ischemia/reperfusion-induced renal injury
      equivalent to GABA (50micromol/kg). These results indicate that GABA prevents the
      development of ischemia/reperfusion-induced acute kidney injury presumably via
      GABA(B) receptor, by suppressing the enhanced renal sympathetic nerve activity
      during ischemia and the increased norepinephrine overflow from renal sympathetic
      nerve ending.

PMID- 19765584
TI  - Differential effects of the antioxidant n-acetylcysteine on the production of
      catabolic mediators in IL-1beta-stimulated human osteoarthritic synoviocytes and
      chondrocytes.
AB  - Oxidative stress may play a relevant role in synovial inflammation and
      subsequently on cartilage damage during osteoarthritis development. We have
      assessed how the antioxidant N-acetylcysteine (NAC) affects the expression of
      different proinflammatory and structural mediators in human stimulated
      osteoarthritic synoviocytes and chondrocytes. Synovial membrane and articular
      cartilage were obtained from the osteoarthritis knees of patients who underwent
      joint replacement surgery. In cells stimulated with IL-1beta (10U/mL), the
      effects of NAC (2mmol/L) were tested at the mean peak plasma level following oral
      administration of therapeutic doses and its influence on prostaglandin E2
      (PGE(2)) production, cyclooxigenase-2 (COX-2) expression, nitric oxide (NO)
      synthesis, nuclear factor kappa B (NF-kappaB) activation, and metalloproteinase-1
      (MMP-1) and metalloproteinase-13 (MMP-13) expression were evaluated. While NAC
      significantly diminished PGE(2) release and the expression of both COX-2 and MMP
      13 protein in IL-1beta-stimulated synoviocytes, it failed to modify their
      production in stimulated chondrocytes. Likewise, NAC only inhibited IL-1beta
      stimulated NF-kappaB activation in synoviocytes. No inhibition of IL-1beta
      induced NO synthesis by chondrocytes was observed following NAC incubation, while
      synoviocytes did not release detectable levels of NO. NAC did not induce changes
      in MMP-1 protein expression in either IL-1beta-stimulated synoviocytes or
      chondrocytes. Thus, NAC decreases the synthesis of several catabolic mediators by
      osteoarthritic synoviocytes, whereas, it failed to produce the same effects in
      osteoarthritic chondrocytes. Our results suggest that NAC inhibits some oxygen
      dependent mechanisms in synoviocytes but not in chondrocytes during
      osteoarthritis. Therefore, NAC might have a symptomatic effect on the synovium
      rather than a structural effect on the cartilage in osteoarthritis.

PMID- 19765585
TI  - Spinal antinociception evoked by the triterpene 3beta, 6beta, 16beta
      trihydroxylup-20(29)-ene in mice: evidence for the involvement of the
      glutamatergic system via NMDA and metabotropic glutamate receptors.
AB  - The present study investigated the possible involvement of the glutamatergic and
      neurokinin systems in the antinociception caused by triterpene 3beta, 6beta,
      16beta-trihydroxylup-20(29)-ene (TTHL) in mice. TTHL given by intraperitoneal
      (i.p., 2.1-65.5micromol/kg), intraplantar (i.pl., 6.5-65.5nmol/paw) or
      intrathecal (i.t., 21.8-655nmol/site) routes, produced dose-dependent inhibition
      of glutamate-induced nociception with ID(50) values of 12micromol/kg;
      34.2nmol/paw; 233.8nmol/site and inhibitions of 78+/-6; 82+/-4 and 77+/-8%,
      respectively. I.t. injection of TTHL (6.5-218nmol/site, co-administered) also
      caused significant and dose-dependent reduction of nociceptive response induced
      by i.t. injection of glutamate (175nmol/site), with ID(50) value of 54.5nmol/site
      and inhibition of 51+/-6%. Moreover, TTHL (65.5nmol/site) co-injected by i.t.
      route with agonist caused marked reduction of nociceptive responses induced by N
      methyl-d-aspartate (NMDA, 450pmol/site), (+/-)-1-aminocyclopentane-trans-1,3
      dicarboxylic acid (trans-ACPD, 10nmol/site) and substance P (100pmol/site), with
      inhibitions of 81+/-7; 79+/-7; 81+/-11%, respectively. Conversely, TTHL had no
      effect on alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA,
      135pmol/site) and kainic acid (kainate, 110pmol/site)-induced nociception.
      Moreover, the association of sub-effective doses of TTHL (6.5nmol/site, i.t.) and
      MK-801(1nmol/site, i.t.; non-competitive NMDA antagonist) or (RS)-MCPG
      (30nmol/site, i.t.; non-selective group I/group II metabotropic glutamate
      receptor antagonist) produced a synergic antinociceptive effect in the
      nociception induced by NMDA or trans-ACPD, respectively. Together, these results
      provide experimental evidence for the involvement of the glutamatergic system
      (NMDA and metabotropic glutamate receptors) in the antinociceptive action caused
      by TTHL in mice.

PMID- 19765586
TI  - Pancreatic tissue protective nature of D-Pinitol studied in streptozotocin
      mediated oxidative stress in experimental diabetic rats.
AB  - The present study was aimed to investigate the possible pancreatic tissue
      protective nature of D-Pinitol, a cyclitol present in soybean, against free
      radical-mediated oxidative stress in streptozotocin-induced diabetic rats by
      assaying the activity of pancreatic enzymatic antioxidants such as superoxide
      dismutase (SOD), catalase, glutathione peroxidase (GPx) and glutathione-S
      transferase (GST) and the levels of plasma non-enzymatic antioxidants such as
      vitamin E, vitamin C, ceruloplasmin and reduced glutathione (GSH). To assess the
      extent of oxidative stress, the levels of lipid peroxidation (LPO) and
      hydroperoxides in both plasma and pancreatic tissues were also measured. A
      significant increase in the levels of both lipid peroxides and hydroperoxides
      with a concomitant decrease in antioxidant status was observed in the diabetic
      rats when compared to control rats. Oral administration of D-Pinitol (50 mg/kg
      b.w./day for 30 days), a major cyclitol present in soybean, ameliorates the free
      radical-mediated alterations to near normalcy. The pancreatic tissue protective
      nature of D-Pinitol was further evidenced by histological observations. The
      results were statistically comparable with glyclazide, a standard hypoglycemic
      drug. Thus, the results of the present study suggest that D-Pinitol protects the
      pancreatic tissue from free radical-mediated oxidative stress in addition to its
      antidiabetic property.

PMID- 19765587
TI  - In vivo study of human Plasmodium knowlesi in Macaca fascicularis.
AB  - Plasmodium knowlesi is a malaria parasite of Old World monkeys and is infectious
      to humans. In this study Macaca fascicularis was used as a model to understand
      the host response to P. knowlesi using parasitological and haematological
      parameters. Three M. fascicularis of either sex were experimentally infected with
      P. knowlesi erythrocytic parasites from humans. The pre-patent period for P.
      knowlesi infection in M. fascicularis ranged from seven to 14 days. The
      parasitemia observed was 13,686-24,202 parasites per microL of blood for asexual
      stage and 88-264 parasites per microL of blood for sexual stage. Periodicity
      analysis adopted from microfilaria periodicity technique of asexual stage showed
      that the parasitemia peak at 17:39h while the sexual stage peaked at 02:36 h.
      Mathematical analysis of the data indicates that P. knowlesi gametocytes tend to
      display periodicity with a peak (24:00-06:00) that coincides with the peak biting
      activity (19:00-06:00) of the local vector, Anopheles latens. The morphology of
      P. knowlesi resembled P. falciparum in early trophozoite and P. malariae in late
      trophozoite. However, it may be distinguishable by observing the applique
      appearance of the cytoplasm and the chromatin lying inside the ring.
      Haematological analysis on macaques with knowlesi malaria showed clinical
      manifestations of hypoglycaemia, anaemia and hyperbilirubinemia. Gross
      examination of spleen and liver showed malaria pigments deposition in both
      organs.

PMID- 19765588
TI  - Nucleoside diphosphate kinase-1 regulates hyphal development via the
      transcriptional regulation of catalase in Neurospora crassa.
AB  - A nucleoside diphosphate kinase-1-disrupted (ndk-1(RIP-1)) mutant was observed to
      be defective in aerial hyphal and conidial development. In this study, two types
      of hyphae, fine and thick, were observed in wild-type (Wt) strains. However, only
      fine-type hyphae were observed in the ndk-1(RIP-1) mutants. The ndk-1(RIP-1)
      mutants were stimulated by oxidative stress and constitutively expressed an
      antioxidant enzyme catalase (CAT)-3. Furthermore the ndk-1(RIP-1) mutants could
      form thick hyphae by oxidative stress and a disruption of cat-3. These results
      suggest that the loss of thick hyphae in the ndk-1(RIP-1) mutants may be caused
      by the over-expression of cat-3.

PMID- 19765589
TI  - Hyperparasitism has wide-ranging implications for studies on the invertebrate
      phase of myxosporean (Myxozoa) life cycles.
AB  - All of the actinospore releasing oligochaetes collected in an environmental
      sample were found to be infected with the microsporidian Neoflabelliforma
      aurantiae n. gen. n. sp. Ultrastructural and phylogenetic studies on this
      microsporidian indicated similarities with Flabelliforma magnivora but not with
      the type species Flabelliforma montana, necessitating the formation of a new
      genus Neoflabelliforma and reassignment of F. magnivora as Neoflabelliforma
      magnivora n. comb. The development of N. aurantiae is described both parasitising
      the oligochaete worm and hyperparasitising the concurrent myxosporean infection.
      The effect of N. aurantiae on the myxosporeans was deleterious and progressive,
      eventually stopping all actinospore formation. Its discovery has the potential to
      impact on areas examining the phase of myxosporean life cycles in the
      invertebrate host, from transmission studies and epidemiology to re-evaluating
      the basic steps of intra-oligochaete development. Recent evidence has suggested
      that studies using invertebrate systems should consider possible adverse effects
      that co-infections can have on experimental outcomes. The discovery of N.
      aurantiae highlights the need for careful screening of experimental animals to
      help circumvent erroneous results.

PMID- 19765590
TI  - Potential epigenetic regulatory proteins localise to distinct nuclear sub
      compartments in Plasmodium falciparum.
AB  - The life cycle of the malaria parasite Plasmodium falciparum involves dramatic
      morphological and molecular changes required for infection of insect and
      mammalian hosts. Stage-specific gene expression is crucial, yet few nuclear
      factors, including potential epigenetic regulators, have been identified.
      Epigenetic mechanisms play an important role in the switched expression of
      members of species-specific gene families, which encode proteins exported into
      the cytoplasm and onto the surface of infected erythrocytes. This includes the
      large virulence-associated var gene family, in which monoallelic transcription of
      a single member and switching to other var genes leads to a display of different
      surface ligands with distinct antigenic and adhesive properties. Using a bio
      informatic approach we identified 24 putative nuclear proteins. Tagging with
      sequences encoding GFP or haemagglutinin (HA) epitopes allowed for identification
      and localisation analysis of 12 nuclear proteins that are potential regulators of
      P. falciparum gene expression. These proteins specifically localise to distinct
      areas of the nucleus, reaching from the centre towards the nuclear envelope,
      giving new insights into the apicomplexan nuclear architecture. Proteins
      presenting a punctate distribution in the perinuclear sub-compartments are
      potential virulence gene regulators as silenced and active var genes reside at
      the nuclear periphery either clustered or in small expression sites,
      respectively. These analyses demonstrated an ordered compartmentalisation,
      indicating a complex sub-nuclear organisation that contributes to the complexity
      of transcriptional regulation in P. falciparum.

PMID- 19765591
TI  - Tracing ancestors and relatives of Escherichia coli B, and the derivation of B
      strains REL606 and BL21(DE3).
AB  - Antecedents of Escherichia coli B have been traced through publications,
      inferences, and personal communication to a strain from the Institut Pasteur in
      Paris used by d'Herelle in his studies of bacteriophages as early as 1918 (a
      strain not in the current collection). This strain appears to have passed from
      d'Herelle to Bordet in 1920, and from Bordet to at least three other laboratories
      by 1925. The strain that Gratia received from Bordet was apparently passed to
      Bronfenbrenner by 1924 and from him to Luria around 1941. Delbruck and Luria
      published the first paper calling this strain B in 1942. Its choice as the common
      host for phages T1-T7 by the phage group that developed around Delbruck, Luria,
      and Hershey in the 1940s led to widespread use of B along with E. coli K-12,
      chosen about the same time for biochemical and genetic studies by Tatum and
      Lederberg. Not all currently available strains related to B are descended from
      the B of Delbruck and Luria; at least three strains with somewhat different
      characteristics were derived independently by Hershey directly from the
      Bronfenbrenner strain, and a strain that appears to have passed from Bordet to
      Wollman is in the current Collection of the Institut Pasteur. The succession of
      manipulations and strains that led from the B of Delbruck and Luria to REL606 and
      BL21(DE3) is given, established in part through evidence from their recently
      determined complete genome sequences.

PMID- 19765592
TI  - Understanding the differences between genome sequences of Escherichia coli B
      strains REL606 and BL21(DE3) and comparison of the E. coli B and K-12 genomes.
AB  - Each difference between the genome sequences of Escherichia coli B strains REL606
      and BL21(DE3) can be interpreted in light of known laboratory manipulations plus
      a gene conversion between ribosomal RNA operons. Two treatments with 1-methyl-3
      nitro-1-nitrosoguanidine in the REL606 lineage produced at least 93 single-base
      pair mutations ( approximately 90% GC-to-AT transitions) and 3 single-base-pair
      GC deletions. Two UV treatments in the BL21(DE3) lineage produced only 4 single
      base-pair mutations but 16 large deletions. P1 transductions from K-12 into the
      two B lineages produced 317 single-base-pair differences and 9 insertions or
      deletions, reflecting differences between B DNA in BL21(DE3) and integrated
      restriction fragments of K-12 DNA inherited by REL606. Two sites showed selective
      enrichment of spontaneous mutations. No unselected spontaneous single-base-pair
      mutations were evident. The genome sequences revealed that a progenitor of REL606
      had been misidentified, explaining initially perplexing differences. Limited
      sequencing of other B strains defined characteristic properties of B and allowed
      assembly of the inferred genome of the ancestral B of Delbruck and Luria.
      Comparison of the B and K-12 genomes shows that more than half of the 3793
      proteins of their basic genomes are predicted to be identical, although
      approximately 310 appear to be functional in either B or K-12 but not in both.
      The ancestral basic genome appears to have had approximately 4039 coding
      sequences occupying approximately 4.0 Mbp. Repeated horizontal transfer from
      diverged Escherichia coli genomes and homologous recombination may explain the
      observed variable distribution of single-base-pair differences. Fifteen sites are
      occupied by phage-related elements, but only six by comparable elements at the
      same site. More than 50 sites are occupied by IS elements in both B and K, 16 in
      common, and likely founding IS elements are identified. A signature of widespread
      cryptic phage P4-type mobile elements was identified. Complex deletions (dense
      clusters of small deletions and substitutions) apparently removed nonessential
      genes from approximately 30 sites in the basic genomes.

PMID- 19765593
TI  - A multi-scale, discrete-cell simulation of organogenesis: Application to the
      effects of strain stimulus on collective cell behavior during ameloblast
      migration.
AB  - A multi-scale strategy is presented for simulating organogenesis that uses a
      single cell response function to define the behavior of individual cells in an
      organ-scale simulation of a large cell population. The response function
      summarizes detailed information about the behavior of individual cells in a
      sufficiently economical way that the organ-scale model can be commensurate with
      the entire organ. The first application demonstrates the effects of strain
      stimulus on the migration of ameloblasts during enamel formation. Ameloblasts are
      an attractive study case because mineralization preserves a complete record of
      their migratory paths. The response function in this case specifies the motions
      of cells responding to strain stimuli that propagate through the population. The
      strain stimuli are related to the curvature of the surface from which the
      ameloblasts migrate (the dentin-enamel junction or DEJ). A single unknown rate
      parameter is calibrated by an independent datum from the human tooth. With no
      remaining adjustable parameters, the theory correctly predicts aspects of the
      fracture-resistant, wavy microstructure of enamel in the human molar, including
      wavelength variations and the rate of wave amplitude damping. At a critical value
      of curvature of the DEJ, a transition in the ordering of cells occurs, from
      invariant order over the whole population to self-assembly of the population into
      groups or gangs. The prediction of an ordering transition and the predicted
      critical curvature are consistent with gnarled enamel in the cusps of the human
      molar. The calibration of the model using human data also predicts waves in the
      mouse incisor and an ordering transition at the chimpanzee cingulum. Widespread
      compressive strain is predicted late in the migration for both the human molar
      and mouse incisor, providing a possible signal for the termination of
      amelogenesis.

PMID- 19765594
TI  - The rational parameterization theorem for multisite post-translational
      modification systems.
AB  - Post-translational modification of proteins plays a central role in cellular
      regulation but its study has been hampered by the exponential increase in
      substrate modification forms ("modforms") with increasing numbers of sites. We
      consider here biochemical networks arising from post-translational modification
      under mass-action kinetics, allowing for multiple substrates, having different
      types of modification (phosphorylation, methylation, acetylation, etc.) on
      multiple sites, acted upon by multiple forward and reverse enzymes (in total
      number L), using general enzymatic mechanisms. These assumptions are
      substantially more general than in previous studies. We show that the steady
      state modform concentrations constitute an algebraic variety that can be
      parameterized by rational functions of the L free enzyme concentrations, with
      coefficients which are rational functions of the rate constants. The
      parameterization allows steady states to be calculated by solving L algebraic
      equations, a dramatic reduction compared to simulating an exponentially large
      number of differential equations. This complexity collapse enables analysis in
      contexts that were previously intractable and leads to biological predictions
      that we review. Our results lay a foundation for the systems biology of post
      translational modification and suggest deeper connections between biochemical
      networks and algebraic geometry.

PMID- 19765595
TI  - The cutaneous intrinsic visceral afferent nervous system: a new model for
      acupuncture analgesia.
AB  - The mechanism of acupuncture, whilst not known with certainty, has previously
      been considered to be stimulatory. A novel hypothesis is presented here in which
      C fiber tactile afferent axons bifurcate at acupuncture points and then diverge,
      running along acupuncture meridians, to subsequently communicate with Merkel
      cells. It is proposed that acupuncture disrupts the bifurcation of these axons,
      preventing neural transmission between Merkel cells as well as central
      communication with the spinal cord. Making use of the known phenomenon that
      acupuncture points have lower electrical resistance than adjacent skin, this
      hypothesis was tested using an electrical circuit model and successfully
      predicted the observed 10(3) reduction in skin resistance at acupuncture points.
      In addition to explaining acupuncture and the roles of both Merkel cells and C
      fiber tactile afferents, the model has greater implications for neuroscience,
      through the postulation of a new division of the autonomic nervous system.

PMID- 19765596
TI  - Alternative stable states in communities with intraguild predation.
AB  - Intraguild predation (IGP) is a widespread ecological phenomenon in which two
      consumers that share a resource also engage in a predator-prey interaction.
      Theory on IGP predicts the occurrence of alternative stable states, but empirical
      evidence of such states is scarce. This raises the question of whether
      alternative states are a rare phenomenon that is unlikely to be observed in
      nature. Here we analyze a model in which the resource exhibits logistic or
      chemostat dynamics and consumers have saturating (Type II) functional responses.
      We show that alternative states can arise for a wide range of biological
      scenarios and that environmental constraints can make their detection difficult.
      Our analysis identifies three possible combinations of alternative states: (i) IG
      prey or IG predator, (ii) coexistence or IG predator, and (iii) coexistence or IG
      prey. Bifurcation diagrams reveal that alternative states are possible over large
      regions of the parameter space. However, they can be limited to narrow ranges
      along the resource productivity axis, which may make it difficult to observe the
      occurrence of alternative states in communities with IGP. Microcosm experiments
      provide a promising avenue for detecting combinations of asymptotically stable
      states along a productivity gradient.

PMID- 19765597
TI  - Norcantharidin is a small-molecule synthetic compound with anti-angiogenesis
      effect.
AB  - AIMS: This study examined the in vitro and in vivo angiogenic effects of
      norcantharidin (NCTD), a synthetic, small-molecule antitumor compound. MAIN
      METHODS: Syngeneic colorectal adenocarcinoma CT26 cells were implanted in mice to
      examine the effect of NCTD on VEGF production and renal and hepatic toxicity.
      Human umbilical endothelial cells (HUVECs) were used to examine the in vitro
      effect of NCTD on viability, chemotaxis, vascular network tube formation,
      adhesive ability, anoikis, and mitogen-activated protein kinase (MAPK) signaling.
      A protein array was used for analysis of angiogenic factors released from NCTD
      treated HUVECs. KEY FINDINGS: NCTD suppressed plasma VEGF levels of tumor-bearing
      mice, without renal or hepatic toxicity. In vitro, NCTD inhibited viability of
      normal HUVECs to a lesser extent than CT26 cancer cells. At concentrations less
      than those inhibiting 50% of the cells, NCTD inhibited migration and capillary
      like tube formation of HUVECs. The anti-angiogenic effect of NCTD was accompanied
      by anoikis, down-regulation of integrin beta1, and breakdown of vimentin. NCTD
      decreased MAPK expression of phosphorylated (p)-JNK and p-ERK. P-P38 expression
      or P38 inhibitor SB203580 did not impair the effect of NCTD on viability or
      adhesion of HUVECs. In addition, NCTD inhibited the release of pro-angiogenic
      factors from HUVECs, but not from CT26 cells. SIGNIFICANCE: NCTD is a synthetic,
      small-molecule compound possessing anti-angiogenetic activity with potential use
      in anti-cancer therapy as an anti-metastatic and anti-angiogenic agent.

PMID- 19765598
TI  - Alterations in gene regulation following inhibition of the striatum-enriched
      phosphodiesterase, PDE10A.
AB  - PDE10A is a member of the phosphodiesterase superfamily highly enriched within
      medium spiny neurons (MSN) in mammalian striatum. We have used inhibitors of
      PDE10A and quantitative measures of mRNA to demonstrate that PDE10A controls
      striatal gene expression by regulating MSN cyclic nucleotide signaling pathways.
      Acute treatment with PDE10A inhibitors produces rapid and transient transcription
      of the immediate early gene cfos in rat striatum. Although inhibition of PDE10A
      causes accumulation of both cAMP and cGMP, the increase in striatal cfos
      expression appears to depend on changes in cAMP, since the increase is present in
      mice deficient in nNOS which fail to increase cGMP in response to PDE10A
      inhibition. Consistent with its expression in a majority of striatal MSN, PDE10A
      inhibition significantly induces expression of both substance P and enkephalin,
      neuropeptide markers for the direct and indirect striatal output pathways,
      respectively. These findings support the hypothesis that PDE10A modulates signal
      transduction in both striatal output pathways and suggest that PDE10A inhibitors
      may offer a unique approach to the treatment of schizophrenia.

PMID- 19765599
TI  - Cocaine exposure modulates dopamine and adenosine signaling in the fetal brain.
AB  - Exposure to cocaine during the fetal period can produce significant lasting
      changes in the structure and function of the brain. Cocaine exerts its effects on
      the developing brain by blocking monoamine transporters and impairing monoamine
      receptor signaling. Dopamine is a major central target of cocaine. In a mouse
      model, we show that cocaine exposure from embryonic day 8 (E8) to E14 produces
      significant reduction in dopamine transporter activity, attenuation of dopamine
      D1-receptor function and upregulation of dopamine D2-receptor function. Cocaine's
      effects on the D1-receptor are at the level of protein expression as well as
      activity. The cocaine exposure also produces significant increases in basal cAMP
      levels in the striatum and cerebral cortex. The increase in the basal cAMP levels
      was independent of dopamine receptor activity. In contrast, blocking the
      adenosine A2a receptor downregulated the basal cAMP levels in the cocaine-exposed
      brain to physiological levels, suggesting the involvement of adenosine receptors
      in mediating cocaine's effects on the embryonic brain. In support of this
      suggestion, we found that the cocaine exposure downregulated adenosine
      transporter function. We also found that dopamine D2- and adenosine A2a-receptors
      antagonize each other's function in the embryonic brain in a manner consistent
      with their interactions in the mature brain. Thus, our data show that prenatal
      cocaine exposure produces direct effects on both the dopamine and adenosine
      systems. Furthermore, the dopamine D2 and adenosine A2a receptor interactions in
      the embryonic brain discovered in this study unveil a novel substrate for
      cocaine's effects on the developing brain.

PMID- 19765601
TI  - From discrete to continuous evolution models: A unifying approach to drift
      diffusion and replicator dynamics.
AB  - We study the large population limit of the Moran process, under the assumption of
      weak-selection, and for different scalings. Depending on the particular choice of
      scalings, we obtain a continuous model that may highlight the genetic-drift
      (neutral evolution) or natural selection; for one precise scaling, both effects
      are present. For the scalings that take the genetic-drift into account, the
      continuous model is given by a singular diffusion equation, together with two
      conservation laws that are already present at the discrete level. For scalings
      that take into account only natural selection, we obtain a hyperbolic singular
      equation that embeds the Replicator Dynamics and satisfies only one conservation
      law. The derivation is made in two steps: a formal one, where the candidate limit
      model is obtained, and a rigorous one, where convergence of the probability
      density is proved. Additional results on the fixation probabilities are also
      presented.

PMID- 19765600
TI  - Functional neuroimaging of self-referential encoding with age.
AB  - Aging impacts memory formation and the engagement of frontal and medial temporal
      regions. However, much of the research to date has focused on the encoding of
      neutral verbal and visual information. The present fMRI study investigated age
      differences in a social encoding task while participants made judgments about the
      self or another person. Although previous studies identified an intact self
      reference effect with age, subserved by robust engagement of medial prefrontal
      cortex (mPFC) by both young and older adults, we identified a number of age
      differences. In regions including superior mPFC, inferior prefrontal cortex, and
      anterior and posterior cingulate cortex, young and older adults exhibited
      reversals in the pattern of activity for self and other conditions. Whereas young
      primarily evidenced subsequent forgetting effects in the self-reference
      condition, older adults demonstrated subsequent memory effects in the other
      reference condition. These results indicate fundamental differences across the
      age groups in the engagement of elaborative encoding processes. We suggest that
      older adults may encode information about the self in a more normative manner,
      whereas young adults focus on encoding the unique aspects of the self and
      distinguishing the self from others.

PMID- 19765602
TI  - The contribution of low-level features at the centre of gaze to saccade target
      selection.
AB  - Does it matter what observers are looking at right now to determine where they
      will look next? We recorded eye movements and computed colour, local orientation,
      motion, and geometrical invariants on dynamic natural scenes. The distributions
      of differences between features at successive fixations were compared with those
      from random scanpaths of varying similarity to natural scanpaths. Although
      distributions show significant differences, these feature correlations are mainly
      due to spatio-temporal correlations in natural scenes and a target selection
      bias, e.g. towards moving objects. Our results indicate that low-level features
      at fixation contribute little to the choice of the next saccade target.

PMID- 19765603
TI  - The watercolor effect: spacing constraints.
AB  - The watercolor effect (WCE) is a long-range color assimilation effect occurring
      within an area enclosed by a light chromatic contour, which in turn is surrounded
      by a dark chromatic contour. Here, we studied the effects of chromatic modulation
      of the WCE for different kinds of spacing between and within the inducing
      contours, using a hue-cancellation method. When an empty zone or interspace was
      inserted between the inducing contours (radial spacing), the hue shift required
      to null the induced coloration rapidly decreased with increasing spacing between
      the two contours. Similarly, when the continuous contours were replaced by dotted
      contours (lateral spacing), the shift in chromaticity quickly decreased with
      increasing distance between the dots. In this case, the decrease was similar for
      chains of paired dots ("in-phase") and chains of unpaired dots ("out-of-phase").
      Results demonstrate that the WCE is strongest when the two inducing contours are
      spatially contiguous and continuous. The neural implications of these findings
      are discussed.

PMID- 19765604
TI  - Suppression pathways saturate with contrast for parallel surrounds but not for
      superimposed cross-oriented masks.
AB  - Contrast masking from parallel grating surrounds (doughnuts) and superimposed
      orthogonal masks have different characteristics. However, it is not known whether
      the saturation of the underlying suppression that has been found for parallel
      doughnut masks depends on (i) relative mask and target orientation, (ii) stimulus
      eccentricity or (iii) surround suppression. We measured contrast-masking
      functions for target patches of grating in the fovea and in the periphery for
      cross-oriented superimposed and doughnut masks and parallel doughnut masks. When
      suppression was evident, the factor that determined whether it accelerated or
      saturated was whether the mask stimulus was crossed or parallel. There are at
      least two interpretations of the asymptotic behaviour of the parallel surround
      mask. (1) Suppression arises from pathways that saturate with (mask) contrast.
      (2) The target is processed by a mechanism that is subject to surround
      suppression at low target contrasts, but a less sensitive mechanism that is
      immune from surround suppression 'breaks through' at higher target contrasts. If
      the mask can be made less potent, then masking functions should shift downwards,
      and sideways for the two accounts, respectively. We manipulated the potency of
      the mask by varying the size of the hole in a parallel doughnut mask. The results
      provided strong evidence for the first account but not the second. On the view
      that response compression becomes more severe progressing up the visual pathway,
      our results suggest that superimposed cross-orientation suppression precedes
      orientation tuned surround suppression. These results also reveal a previously
      unrecognized similarity between surround suppression and crowding (Pelli,
      Palomares, & Majaj, 2004).

PMID- 19765605
TI  - Smoking mice: a potential model for studying accumulation of drusen-like material
      on Bruch's membrane.
AB  - Currently, there are no animal models that can be used to test pharmacological
      efficacy of drugs that are under development for treating dry AMD. We suggest
      measuring the accumulation of a panel of drusen-like proteins on Bruch's membrane
      in mice as a surrogate endpoint to test pharmacological modulation of the course
      of drusen formation. We further suggest that the buildup of proteins on Bruch's
      membrane in the RPE/choroid in "smoking mice" can be used as a surrogate model
      for pharmacological studies and that using these mice will significantly decrease
      the time frame for demonstrating pharmacological efficacy of lead compounds.

PMID- 19765606
TI  - Illusory position shift induced by plaid motion.
AB  - In the motion-induced position shift (MIPS), the position of a moving pattern
      tapered by a stationary envelope is perceived to shift in the direction of the
      motion. It was found that plaid motion also elicited a MIPS in the direction of
      global motion and this global MIPS could not be predicted by the average of the
      local MIPSs due to component motions. We also used a pseudo plaid pattern and
      again observed a global MIPS that could not be predicted by the local MIPSs due
      to the components of the pseudo plaid pattern. We suggest the possibility that
      the receptive-field positions of global motion detectors shift in the direction
      opposite to global motion, resulting in a positional displacement in activation
      via population coding.

PMID- 19765607
TI  - Expression and regulation of enzymes in the ceramide metabolic pathway in human
      retinal pigment epithelial cells and their relevance to retinal degeneration.
AB  - Ceramide and its metabolic derivatives are important modulators of cellular
      apoptosis and proliferation. Dysregulation or imbalance of their metabolic
      pathways may promote the development of retinal degeneration. The aim of this
      study was to identify the expression and regulation of key enzymes of the
      ceramide pathway in retinal pigment epithelial (RPE) cells. RT-PCR was used to
      screen the enzymes involved in ceramide metabolism that are expressed in RPE.
      Over-expression of neutral sphingomyelinase-2 (SMPD3) or sphingosine kinase 1
      (Sphk1) in ARPE-19 cells was achieved by transient transfection of SMPD3 or Sphk1
      cDNA subcloned into an expression vector. The number of apoptotic or
      proliferating cells was determined using TUNEL and BrdU assays, respectively.
      Neutral sphingomyelinase-1, neutral sphingomyelinase-2, acidic ceramidase,
      ceramide kinase, SphK1 and Sphk2 were expressed in both ARPE-19 and early passage
      human fetal RPE (fRPE) cells, while alkaline ceramidase 2 was only expressed in
      fRPE cells. Over-expression of SMPD3 decreased RPE cell proliferation and
      increased cell apoptosis. The percentage of apoptotic cells increased
      proportionally with the amount of transfected SMPD3 DNA. Over-expression of SphK1
      promoted cell proliferation and protected ARPE-19 cells from ceramide-induced
      apoptosis. The effect of C(2) ceramide on induction of apoptosis was evaluated in
      polarized vs. non-polarized RPE cultures; polarization of RPE was associated with
      much reduced apoptosis in response to ceramide. In conclusion, RPE cells possess
      the synthetic machinery for the production of ceramide, sphingosine, ceramide-1
      phosphate (C1P), and sphingosine-1-phosphate (S1P). Over-expression of SMPD3 may
      increase cellular ceramide levels, leading to enhanced cell death and arrested
      cell proliferation. The selective induction of apoptosis in non-polarized RPE
      cultures by C(2) ceramide suggests that increased ceramide levels will
      preferentially affect non-polarized RPE, as are found in late age-related macular
      degeneration lesions, and may spare the normal RPE monolayer. SphK1 over
      expression increased cellular S1P, which promoted cell proliferation and
      protected RPE from ceramide-induced apoptosis. Understanding the relationship
      between the metabolism of sphingolipids and their effects in RPE cell
      survival/death may help us to develop effective and efficient therapies for
      retinal degeneration.

PMID- 19765608
TI  - Boy Scout 5-a-Day Badge: outcome results of a troop and Internet intervention.
AB  - OBJECTIVES: The effects of a Boy Scout Five-A-Day Badge program on fruit juice
      (FJ) and low-fat vegetable (LV) consumption were evaluated using a two-condition
      (treatment, active-attention-placebo-control) group randomized trial, with three
      data collection periods (baseline, immediate post, 6-month post). METHODS: Forty
      two Boy Scout troops (n=473, 10- to 14-year-old Scouts) in Houston, TX, were
      randomly assigned to condition. The 9-week program included approximately 30 min
      of weekly troop time, plus approximately 25 min of weekly Internet programming.
      The intervention was delivered in two waves (Spring and Fall). Data were
      collected in 2003-2004, and analyses were completed in 2008. Main outcomes were
      FJ and LV consumption (validated food frequency questionnaire). FV self-efficacy,
      preferences, and home availability were also measured. RESULTS: Significant
      increases in FJ consumption (p=.003), FJ home availability (p=.009), and LV self
      efficacy (p=.004) were observed among the intervention group immediately
      following the intervention but were not maintained 6 months later. CONCLUSION: A
      Boy Scout troop-plus-Internet intervention promoting FJ and LV consumption
      resulted in short-term changes in FJ consumption among U.S. Boy Scouts. Future
      research should investigate ways to extend these results to LV and maintain the
      increases over time.

PMID- 19765609
TI  - Are gender differences in colorectal cancer screening rates due to differences in
      self-reporting?
AB  - OBJECTIVE: Studies have found that women are less likely than men to undergo
      colorectal cancer (CRC) screening. While one source of these disparities may be
      gender differences in barriers and facilitators to screening, another may be
      differences in reporting bias. METHOD: In this study of 345 male and female
      veterans, conducted in 2006 in Minneapolis, MN, we examined CRC screening
      adherence rates by gender using medical records and self-report and assessed
      whether any differences were due to reporting bias. RESULTS: We found a
      significantly higher rate of colonoscopy use among men when using self-report
      data, but no significant differences in either overall or test-specific screening
      adherence when using medical record data. Analyses examining the prevalence and
      determinants of concordance between self-report and medical records screening
      revealed that compared to women, men were less accurate in reporting
      sigmoidoscopy and colonoscopy and over-reported screening by colonoscopy. Men
      were also more likely to have missing self-report data and how missing data were
      handled affected differences in screening behavior. Accuracy in screening
      behavior was not explained by demographic variables, good physical or mental
      health, or physician recommendation for screening. CONCLUSIONS: Reported gender
      disparities in CRC screening adherence may be a result of reporting bias.

PMID- 19765610
TI  - Infrastructure, programs, and policies to increase bicycling: an international
      review.
AB  - OBJECTIVES: To assess existing research on the effects of various interventions
      on levels of bicycling. Interventions include infrastructure (e.g., bike lanes
      and parking), integration with public transport, education and marketing
      programs, bicycle access programs, and legal issues. METHODS: A comprehensive
      search of peer-reviewed and non-reviewed research identified 139 studies. Study
      methodologies varied considerably in type and quality, with few meeting rigorous
      standards. Secondary data were gathered for 14 case study cities that adopted
      multiple interventions. RESULTS: Many studies show positive associations between
      specific interventions and levels of bicycling. The 14 case studies show that
      almost all cities adopting comprehensive packages of interventions experienced
      large increases in the number of bicycle trips and share of people bicycling.
      CONCLUSIONS: Most of the evidence examined in this review supports the crucial
      role of public policy in encouraging bicycling. Substantial increases in
      bicycling require an integrated package of many different, complementary
      interventions, including infrastructure provision and pro-bicycle programs,
      supportive land use planning, and restrictions on car use.

PMID- 19765611
TI  - Detection of low level histamine H3 receptor occupancy by autoradiography.
AB  - Histamine H(3) receptor antagonists have been proposed as a novel approach to the
      treatment of cognitive, attentional, and sleep disorders. It is apparent that
      H(3) receptor antagonists produce in vivo effects in preclinical animal models of
      central diseases across a wide dose range. In order to characterize the
      relationship between efficacy in the preclinical models and H(3) receptor
      occupancy, a brain slice receptor autoradiography method was used. Brain slice
      receptor autoradiography requires less in vitro tissue processing, preserves
      brain structure, and provides anatomical localization of compound in the brain.
      Consistent with H(3) receptor distribution, in vitro autoradiography experiments
      demonstrated specific binding of [(3)H]NAMH (N-alpha-methylhistamine) in rat
      cortex, and other brain regions, but not in cerebellum. Ex vivo H(3)R brain slice
      autoradiography was able to detect H(3) receptor occupancy by reference
      antagonists at doses lower than previously found using a homogenate assay format.
      The method is relatively quick with image acquisition on a beta-imager and is
      capable of detecting receptor occupancy in different brain regions
      simultaneously. Furthermore, the increased sensitivity should be useful in
      providing dosing guidelines for H(3) antagonists in both preclinical and clinical
      settings.

PMID- 19765612
TI  - A quantitative approach to the dynamics of neurite sprouting induced by a
      neurotrophic factor.
AB  - The sprouting, stabilization and growth of neurites is a dynamic process by which
      developing neurons establish connections with the other elements of the nervous
      system; this process is under the control of extracellular cues, among which
      neurotrophic factors play a crucial role. Due to the complexity of the
      spatiotemporal evolution of the neurite network, particularly in the early stages
      of growth, it is not easy to obtain information about the relevant parameters
      from qualitative observations. We have developed a quantitative description of
      the dynamics of production and stabilization of neuritic processes in a well
      characterized experimental model of peripheral neurons in culture, and we have
      combined it with a simulation approach to extract the differences between the
      behaviour in the absence and in the presence of the neurotrophic factor basic
      Fibroblast Growth Factor (bFGF). We show that the factor rapidly stabilizes the
      neuronal morphology to a bipolar phenotype, by shifting the sprouting process
      from a disordered phase to a more ordered and organized one.

PMID- 19765613
TI  - Practical tools for analysing rhythmic neural activity.
AB  - This report describes an integrated software package, DataView, which contains a
      number of tools for analysing rhythmic neural activity. These include simple
      autocorrelation, a merge-and-drop filter, an enhanced version of the Poisson
      surprise method and a flexible hill-and-valley analysis tool. The package
      contains facilities for identifying, examining, and if appropriate, correcting,
      outliers arising from misidentification or rhythm abnormalities. The package has
      a full graphical user interface which provides flexible and rapid feedback on the
      progress of analysis, and the consequences of choices regarding parameters for
      the various tools. The user can thus easily experiment with different
      methodologies and tool settings, and tune the analysis to the most appropriate
      form for the data in question.

PMID- 19765614
TI  - Low-cost, high-fidelity, adaptive cancellation of periodic 60 Hz noise.
AB  - A common method to eliminate unwanted power line interference in neurobiology
      laboratories where sensitive electronic signals are measured is with a notch
      filter. However a fixed-frequency notch filter cannot remove all power line noise
      contamination since inherent frequency and phase variations exist in the
      contaminating signal. One way to overcome the limitations of a fixed-frequency
      notch filter is with adaptive noise cancellation. Adaptive noise cancellation is
      an active approach that uses feedback to create a signal that when summed with
      the contaminated signal destructively interferes with the noise component leaving
      only the desired signal. We have implemented an optimized least mean square
      adaptive noise cancellation algorithm on a low-cost 16 MHz, 8-bit microcontroller
      to adaptively cancel periodic 60 Hz noise. In our implementation, we achieve
      between 20 and 25 dB of cancellation of the fundamental 60 Hz noise component.

PMID- 19765615
TI  - Nutritional state influences Nociceptin/Orphanin FQ peptide receptor expression
      in the dorsal raphe nucleus.
AB  - Agonists of the nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor stimulate
      food intake. Concordantly, neuroanatomical localization of NOP receptor mRNA has
      revealed it to be highly expressed in brain regions associated with the
      regulation of energy balance. However, the specific mechanisms and neurochemical
      pathways through which physiological N/OFQ influences appetite are not well
      understood. To investigate this, we examined nutritional state-associated changes
      in NOP receptor mRNA levels throughout the rostrocaudal extent of the rat brain
      using in situ hybridization histochemistry (ISHH) and quantitative densitometry
      analysis. We observed a significant downregulation of NOP receptor mRNA in the
      dorsal raphe nucleus (DRN) of fasted rats compared to free-feeding rats. In
      contrast, no difference in NOP receptor mRNA expression was observed in the
      supraoptic, parventricular, ventromedial, arcuate or dorsomedial nuclei of the
      hypothalamus, the red nucleus, the locus coeruleus or the hypoglossal nucleus in
      the fasted or fed state. These data suggest that the endogenous N/OFQ system is
      responsive to changes in energy balance and that NOP receptors specifically
      within the DRN may be physiologically relevant to N/OFQ's effects on appetite.

PMID- 19765616
TI  - Early differences in epithalamic left-right asymmetry influence lateralization
      and personality of adult zebrafish.
AB  - The habenulae are part of an evolutionary conserved conduction system that
      connects the limbic forebrain areas with midbrain structures and is implicated in
      important functions such as feeding, mating, avoidance learning, and hormonal
      response to stress. Very early during zebrafish neurogenesis the parapineal organ
      migrates near to one habenula, commonly the left, inducing wide left-right
      habenular asymmetries in gene expression and connectivity. It was posited that
      this initial symmetry-breaking event determines the development of lateralized
      brain functions and early differences in epithalamic left-right asymmetry give
      rise to individual variation in coping styles and personality. We tested these
      two hypotheses by sorting zebrafish with left or right parapineal at birth using
      a foxD3:GFP marker and by measuring visual and motor laterality and three
      personality dimensions as they become adults. Significant differences between
      fish with opposite parapineal position were found in all laterality tests while
      the influence of asymmetry of the habenulae on personality was more complex. Fish
      with atypical right parapineal position, tended to be bolder when inspecting a
      predator, spent less time in the peripheral portion of an open field and covered
      a shorter distance when released in the dark. Activity in the open field was not
      associated to anatomical asymmetry but correlated with laterality of predator
      inspection that in turn was influenced by parapineal position. One personality
      dimension, sociality, appeared uncorrelated to both anatomical and functional
      asymmetries and was instead influenced by the sex of the fish, thus suggesting
      that other factors, i.e. hormonal, may be implicated in its development.

PMID- 19765617
TI  - Adolescent male Wistar rats are more responsive than adult rats to the
      conditioned rewarding effects of intravenously administered nicotine in the place
      conditioning procedure.
AB  - The initiation of smoking typically begins during adolescence, suggesting that
      nicotine may have different motivational effects during this developmental stage
      compared to adulthood. Studies using the conditioned place preference (CPP)
      procedure have demonstrated that adolescent rats are more sensitive to the
      conditioned rewarding effects of subcutaneously administered nicotine compared to
      adult rats, whereas intravenous self-administration studies have not demonstrated
      consistent age differences in the reinforcing effects of nicotine. This study was
      designed to evaluate if intravenously administered nicotine has age-dependent
      conditioned rewarding effects. Using an unbiased CPP procedure, adolescent and
      adult male Wistar rats were conditioned with one of two intravenous doses of
      nicotine that are sufficient to maintain self-administration (0.03 or 0.06 mg/kg)
      or vehicle (saline) over a period of 8 conditioning trials (4 nicotine and 4
      vehicle). Adolescent rats conditioned with 0.03 mg/kg nicotine demonstrated a
      significant CPP, whereas adult rats did not at either dose tested. After 8
      extinction trials, reinstatement of the CPP was observed following a nicotine
      priming injection (0.15 mg/kg, s.c.) in adolescents that had previously been
      conditioned with 0.03 mg/kg nicotine; vehicle-treated rats did not show a
      significant preference for either compartment. The present data are consistent
      with previous CPP studies using subcutaneously administered nicotine and suggest
      that passively administered intravenous nicotine is more rewarding in adolescent
      compared to adult rats.

PMID- 19765618
TI  - FGF1 nuclear translocation is required for both its neurotrophic activity and its
      p53-dependent apoptosis protection.
AB  - Fibroblast growth factor 1 (FGF1) is a differentiation and survival factor for
      neuronal cells both in vitro and in vivo. FGF1 activities can be mediated not
      only by paracrine and autocrine pathways involving FGF receptors but also by an
      intracrine pathway, which is an underestimated mode of action. Indeed, FGF1 lacks
      a secretion signal peptide and contains a nuclear localization sequence (NLS),
      which is consistent with its usual intracellular and nuclear localization. To
      progress in the comprehension of the FGF1 intracrine pathway in neuronal cells,
      we examined the role of the nuclear translocation of FGF1 for its neurotrophic
      activity as well as for its protective activity against p53-dependent apoptosis.
      Thus, we have transfected PC12 cells with different FGF1 expression vectors
      encoding wild type or mutant (Delta NLS) FGF1. This deletion inhibited both FGF1
      nuclear translocation and FGF1 neurotrophic activity (including differentiation
      and serum-free cell survival). We also show that endogenous FGF1 protection of
      PC12 cells against p53-dependent cell death requires FGF1 nuclear translocation.
      Strikingly, wild type FGF1 is found interacting with p53, in contrast to the
      mutant FGF1 deleted of its NLS, suggesting the presence of direct and/or indirect
      interactions between FGF1 and p53 pathways. Thus, we present evidences that FGF1
      may act by a nuclear pathway to induce neuronal differentiation and to protect
      the cells from apoptosis whether cell death is induced by serum depletion or p53
      activation.

PMID- 19765619
TI  - Multi-locus variable number tandem repeat analysis for Escherichia coli causing
      extraintestinal infections.
AB  - Discriminatory genotyping methods for the analysis of Escherichia coli other than
      O157:H7 are necessary for public health-related activities. A new multi-locus
      variable number tandem repeat analysis protocol is presented; this method
      achieves an index of discrimination of 99.5% and is reproducible and valid when
      tested on a collection of 836 diverse E. coli.

PMID- 19765620
TI  - Improved gene disruption method and Cre-loxP mutant system for multiple gene
      disruptions in Hansenula polymorpha.
AB  - In H. polymorpha, there is still a lack of a highly efficient gene disruption
      method. To help address this issue, we presented a simple and efficient method
      for both single and multiple gene disruptions in H. polymorpha. The knockout
      system combined a variation of sticky-end polymerase chain reaction method (SEP),
      split marker deletion method, co-transformation of single-stranded DNA and mutant
      Cre-loxP system. Using a slightly modified LiAc/SS-DNA/PEG procedure, the co
      transformation double-stranded split marker constructs together with single
      stranded split marker constructs resulted in at least 70% homologous
      recombination events when the homologous genomic DNA fragment had a size of
      approximately 500bp. Our evidence suggested that single-stranded DNA may be
      responsible for the increased gene disruption efficiency. We demonstrated the
      effectiveness of the method for gene disruption by constructing both single and
      double gene disruptions at the ALG3 and URA5 loci in the same genetic background.
      The method described here presents an improved strategy for gene disruption and a
      potential application for investigation of biological processes in other yeast
      strains.

PMID- 19765621
TI  - Tobacco smoking produces widespread dominant brain wave alpha frequency
      increases.
AB  - The major pharmacological ingredient in tobacco smoke is nicotine, a mild
      stimulant known to alter brain electrical activity. The objective of this study
      was to determine if tobacco smoking in humans produces localized or widespread
      neocortical dominant alpha electroencephalographic (EEG) frequency increases
      consistent with nicotine stimulation of the brainstem activating system in
      animals. Twenty-two male volunteer non-deprived tobacco smokers were studied.
      They were asked not to smoke for at least 1h before the experiment in mid-morning
      as part of their usual smoking schedule. In the laboratory, they sham smoked and
      then smoked their favorite tobacco cigarette. Two experimental sessions (#1 and
      #2) were conducted, separated by a one to two month interval. In both sessions,
      there were minor statistically significant increases in the dominant alpha
      frequencies after sham smoking. In both sessions, after the subjects smoked a
      favorite tobacco cigarette there was a significant generalized increase in
      dominant alpha EEG frequencies in most scalp recording sites. This study
      demonstrates that tobacco smoking produces widespread bilateral neocortical
      increases in dominant alpha EEG frequencies consistent with the stimulant effects
      of nicotine on the brainstem reticular activating system.

PMID- 19765622
TI  - What can Event-related Potentials tell us about language, and perhaps even
      thought, in schizophrenia?
AB  - Disturbances of thought and language are fundamental to schizophrenia. Cognitive
      behavioral and electrophysiological research has implicated problems in two
      different neurocognitive mechanisms: abnormalities in the structure and function
      of semantic memory, and abnormalities in combining and integrating words together
      to build up sentence and discourse context. This review discusses recent
      electrophysiological evidence suggesting that these two deficits are not
      completely distinct, but rather that language impairment in schizophrenia results
      from a dysfunctional interaction between these systems in an effort to build up
      higher-order meaning. Moreover, although language abnormalities are more
      pronounced in patients with positive thought disorder, they manifest themselves
      in all patients when increased demands are placed on the comprehension system.
      Further investigation of language dysfunction may also provide insights into
      other aspects of psychotic thought.

PMID- 19765623
TI  - Neuroimaging of semantic processing in schizophrenia: a parametric priming
      approach.
AB  - The use of fMRI and other neuroimaging techniques in the study of cognitive
      language processes in psychiatric and non-psychiatric conditions has led at times
      to discrepant findings. Many issues complicate the study of language, especially
      in psychiatric populations. For example, the use of subtractive designs can
      produce misleading results. We propose and advocate for a semantic priming
      parametric approach to the study of semantic processing using fMRI methodology.
      Implications of this parametric approach are discussed in view of current
      functional neuroimaging research investigating the semantic processing
      disturbance of schizophrenia.

PMID- 19765624
TI  - Understanding the propensity of consumers to comply with dietary guidelines
      directed at heart health.
AB  - The aim of this paper is to explore the difficulty faced by consumers in
      complying with health-related dietary guidelines, focusing on those guidelines
      that consumers find it more/less difficult to meet and the factors driving the
      ability to make associated dietary changes. Participants reported self-assessed
      compliance with 12 dietary recommendations predominantly directed at reducing the
      risk of heart disease. The difficulty of complying with each of the dietary
      guidelines was measured using a Rasch model, while the determinants of ability to
      comply with the dietary recommendations as a whole were identified using
      regression analysis. The more difficult dietary recommendations included limiting
      consumption of red meats and consuming the recommended daily intake of fruits and
      vegetables. Attitudinal variables associated with food, nutrition and health,
      perception of cholesterol risk and a range of socio-demographic variables,
      including age, gender and education, were significant determinants of person
      ability to comply with the dietary recommendations. The results show that there
      are significant differences in the difficulty faced by consumers in complying
      with particular dietary recommendations, while there is substantial variation in
      the ability to eat a healthy diet across participants.

PMID- 19765625
TI  - What constitutes food variety? Stimulus specificity of food.
AB  - Variety is a major influence of energy intake, but it is not known how much foods
      have to vary to influence eating. Using a stimulus specificity habituation
      paradigm we assessed the influence of varying the texture and appearance of
      nutritionally identical foods on responding for food and energy intake, and
      whether sensitization, or an increase in responding prior to habituation, was
      related to the rate of habituation or recovery of responding. Children responded
      for elbow macaroni and cheese until they habituated, then were provided either
      more elbow macaroni and cheese, spiral macaroni and cheese, or chicken nuggets.
      Children provided chicken nuggets or spiral macaroni and cheese recovered
      responding in comparison to more elbow macaroni and cheese. Children who
      sensitized showed slower habituation and consumed more food and more energy than
      those who did not sensitize, but did not differ in recovery of responding to the
      chicken nuggets or spiral macaroni and cheese. Results show small variations in
      food characteristics lead to recovery of responding and increased intake after
      children have habituated.

PMID- 19765626
TI  - Gene expression of (pro)renin receptor is upregulated in hearts and kidneys of
      rats with congestive heart failure.
AB  - Recent studies have revealed that (pro)renin receptor ((P)RR), a newly identified
      member of the renin-angiotensin system, was associated with organ damage in the
      kidney. However, there has been little information for (P)RR in hearts. To
      investigate the regulation of (P)RR in heart failure, we examined the expression
      of (P)RR in hearts and kidneys of rats with congestive heart failure (CHF) due to
      coronary ligation by quantitative RT-PCR and immunohistochemistry. Significantly
      increased levels of (P)RR mRNA were found in the atrium, right ventricle, non
      infarcted part of left ventricle, infarcted part of left ventricle and kidney of
      CHF rats, when compared with sham operated rats (about 1.6-fold, 1.4-fold, 1.6
      fold, 1.7-fold and 1.5-fold, respectively). Expression levels of mRNAs encoding
      renin and angiotensinogen in these heart and kidney tissues were also increased
      in the CHF rats. Immunohistochemistry showed positive (P)RR immunostaining in the
      myocardium, the renal tubular cells, and vascular smooth muscle and endothelial
      cells in the heart and the kidney. The renal tubular cells were more intensely
      immunostained in CHF rats than in sham operated rats. These findings suggest that
      the expression of (P)RR is increased in the hearts and kidneys of rats with heart
      failure, and that (P)RR may contribute to heart failure.

PMID- 19765627
TI  - Novel peptide mimetic small molecules of the HAV motif in N-cadherin inhibit N
      cadherin-mediated neurite outgrowth and cell adhesion.
AB  - The cell adhesion molecule, N-cadherin, stabilizes cell-cell junctions and
      promotes cellular migration during tissue morphogenesis in development. N
      cadherin is also implicated in mediating tumor progression and metastasis in
      cancer. Therefore, developing antagonists of N-cadherin adhesion may be of
      therapeutic value in cancer treatment. The amino acid sequence HAV in the
      extracellular domain of N-cadherin is required for N-cadherin-mediated adhesion
      and migration. A cyclic peptide, ADH-1, derived from the N-cadherin HAV site is
      an effective antagonist of N-cadherin-mediated processes and is now in clinical
      trials for cancer chemotherapy. Because it is a peptide, ADH-1 has certain
      limitations as a drug, namely its metabolic instability and lack of oral
      delivery. Adherex set out to identify small molecule antagonists of N-cadherin,
      which would be more amenable to therapeutic use. Using three-dimensional
      computational screening, Adherex identified a set of small molecules as potential
      antagonists with sufficient structural similarity to the HAV region of N
      cadherin. We tested the ability of these small molecules to interfere with two N
      cadherin-dependent processes: neurite outgrowth (axonal migration) and N-cadherin
      dependent cell adhesion. We identified 21 N-cadherin antagonists of varying
      potency. More importantly, our studies demonstrate that these compounds are
      significantly more potent than ADH-1 at perturbing N-cadherin-mediated processes.
      The IC(50) of ADH-1 is 2.33 mM while the IC(50) of the small molecules ranges
      from 4.5 to 30 microM. Given the efficacy of ADH-1 for treating cancer, these
      small molecule antagonists will be highly effective in treatment of cancer
      metastasis and conditions of aberrant neurite outgrowth, such as neuropathic
      pain.

PMID- 19765628
TI  - Melanin-concentrating hormone. Editorial.

PMID- 19765629
TI  - Acute neurobehavioral effects of toluene: involvement of dopamine and NMDA
      receptors.
AB  - Toluene, a widely used and commonly abused organic solvent, causes a variety of
      behavioral disturbances in both humans and animals. In this study, the effects of
      toluene on locomotor activity, motor coordination, and passive avoidance
      learning, along with the possible mechanism underlying these toluene-induced
      behavioral manifestations, were investigated. Sprague-Dawley rats were tested in
      the open field test, rotarod test, and step-through avoidance learning task after
      receiving toluene (250-750 mg/kg, i.p.). Toluene dose-dependently produced
      locomotor hyperactivity, motor incoordination, and memory impairment. In order to
      determine the possible roles of dopamine and NMDA receptors in these behavioral
      responses to toluene, dopamine D1 receptor antagonist SCH23390, D2 receptor
      antagonist raclopride, D3 receptor antagonist nafadotride, or d-serine, a co
      agonist at the glycine binding site of NMDA receptors, were given prior to
      toluene administration. SCH23390, raclopride, and nafadotride attenuated
      locomotor hyperactivity, but not motor incoordination and memory impairment in
      response to toluene, whereas d-serine reduced all the toluene-induced behavioral
      alterations. These findings suggest that blockade of NMDA receptors may play a
      critical role in acute toluene-induced locomotor hyperactivity, motor
      incoordination, and memory impairment, and that dopamine neurotransmission may be
      specifically involved in locomotor hyperactivity.

PMID- 19765630
TI  - The role of childhood abuse in HPA-axis reactivity in Social Anxiety Disorder: a
      pilot study.
AB  - BACKGROUND: Studies on depression have found that childhood abuse (CA) is
      associated with a persistent sensitization of the hypothalamic-pituitary-adrenal
      (HPA)-axis to stress in adulthood. So far, it is unknown whether this HPA-axis
      sensitization is specific to depression, or whether this is a more general
      outcome associated with CA in patients with mood and anxiety disorders. The aim
      of this study was to investigate whether CA is associated with enhanced cortisol
      reactivity to psychosocial stress in Social Anxiety Disorder (SAD). METHODS:
      Salivary cortisol levels before, during, and after exposure to psychosocial
      stress (i.e., Trier Social Stress Task, TSST) in SAD patients with a history of
      childhood abuse (SAD+CA, n=9) were compared to cortisol levels in SAD patients
      without a history of childhood abuse (SAD-CA, n=9), patients with PTSD related to
      childhood abuse (n=16), and healthy controls without a history of childhood abuse
      (n=16). RESULTS: Analyses showed that the SAD+CA group had a strongly increased
      cortisol reactivity (mean peak: 17.5+/-1.9 nmol/l) compared to SAD-CA (mean peak:
      9.0+/-1.1 nmol/l), PTSD (mean peak: 9.0+/-1.1 nmol/l) and healthy controls (mean
      peak: 9.6+/-1.4 nmol/l), whereas baseline cortisol levels did not differ. The
      enhanced increase in the SAD+CA group was not explained by stronger anxiety in
      response to the TSST. CONCLUSIONS: Consistent with the findings in depression,
      these results show for the first time that childhood abuse is also associated
      with strongly increased cortisol reactivity in SAD. When replicated in a larger
      sample, these findings may have important implications for the treatment of SAD.

PMID- 19765631
TI  - Thyroid hormone action during brain development: more questions than answers.
AB  - Thyroid hormone is essential for proper brain development since it acts on
      processes such as neuronal migration and differentiation, myelination and
      synaptogenesis. In this review, we summarize the consequences of thyroid hormone
      deficiency for brain development with special focus on the cerebellum, an
      important target of thyroid action. In addition, we discuss the role of
      iodothyronine deiodinases and thyroid hormone transporters in regulating local
      thyroid hormone concentrations as well as current knowledge about the function of
      thyroid hormone receptors and their target genes during brain maturation. Despite
      considerable progress in recent years in deciphering thyroid hormone signaling
      pathways we still know very little on the molecular level by which mode of action
      thyroid hormone exerts its cell-specific effects. Hence, we will particularly
      address the open questions that remain to be addressed in order to better
      understand the role of thyroid hormone in brain development.

PMID- 19765632
TI  - Mechanism of VEGF expression by high glucose in proximal tubule epithelial cells.
AB  - Angiotensin II (Ang II) and vascular endothelial growth factor (VEGF) are
      important mediators of kidney injury in diabetes. VEGF expression is increased in
      proximal tubules of mice with type 1 diabetes. In mouse proximal tubular
      epithelial cells (MCT) cultured with 30 mM glucose (HG) for 24h, VEGF expression
      is increased at the protein and the mRNA level, suggesting a transcriptional
      mechanism. HG stimulation of VEGF synthesis is prevented by captopril, an
      inhibitor of angiotensin-converting enzyme, and, by losartan, a specific
      antagonist of angiotensin type 1 receptor (AT1), suggesting that VEGF synthesis
      is mediated by Ang II. Synthesis of angiotensinogen (AGT), a precursor of
      angiotensin II, is increased in MCTs cultured in HG. Although synthesis of renin
      and ACE is not affected by HG, their activity is increased in the conditioned
      medium. Concentrations of Ang I and Ang II are also increased in conditioned
      medium from HG-treated MCTs and captopril prevents increased Ang II, but not Ang
      I, synthesis. Finally, AT1 is activated in MCTs treated with HG, and its
      activation is prevented by captopril and losartan. The ERK pathway is activated
      by HG within minutes of stimulation and lasting for up to 24h. The initial phase
      of ERK activation is due to HG itself and leads to AGT upregulation and the
      sustained phase is mediated for the most part by Ang II-activated AT1 receptor
      and leads to increased VEGF synthesis. These data show that: (1) HG increases AGT
      synthesis and activation of renin and ACE by MCTs, leading to local production of
      Ang I and Ang II. (2) Ang II activates endogenous AT1 and stimulates synthesis of
      VEGF. (3) HG activation of ERK starts within minutes and lasts for up to 24h.
      Early ERK activation is involved in AGT upregulation and sustained ERK
      activation, mediated via AT1, is responsible for VEGF synthesis. In conclusion,
      our study shows that MCTs express an endogenous renin-angiotensin system that is
      activated by high glucose to stimulate the synthesis of VEGF, through activation
      of the ERK pathway.

PMID- 19765633
TI  - Levels of neuregulin 1 and 3 proteins in Brodmann's area 46 from subjects with
      schizophrenia and bipolar disorder.
AB  - Neuregulin (NRG) 1Ialpha and NRG3 proteins levels were measured in Brodmann's
      area 46 from 20 subjects with schizophrenia, 8 subjects with bipolar 1 disorder
      and 20 age-sex matched control subjects. Protein levels of both NRG1Ialpha and
      NRG3 were unchanged in both psychiatric illnesses. These data suggest any change
      in NRG1Ialpha and NRG3 expression in schizophrenia or bipolar 1 disorder do not
      result in changes levels in levels of those proteins Brodmann's area 46.

PMID- 19765634
TI  - Ubc9 gene polymorphisms and late-onset Alzheimer's disease in the Korean
      population: a genetic association study.
AB  - Ubiquitin-conjugating enzyme E2I (Ubc9) ligates small ubiquitin-related modifier
      (SUMO) to target proteins, resulting in changes of their localization, activity,
      or stability. Sumoylation of amyloid precursor protein (APP) was reported to be
      associated with decreased levels of beta amyloid (Abeta) aggregates, suggesting
      that sumoylation may play a role in the pathogenesis of Alzheimer's disease (AD).
      We investigated the association between genetic variations of Ubc9 gene (UBE2I)
      and late-onset Alzheimer's disease (AD). Five single nucleotide polymorphisms
      (SNPs) in UBE2I were genotyped in the DNA samples of 312 AD patients, 347
      subjects with mild cognitive impairment (MCI), and 489 cognitively healthy
      controls. The genotype distribution of a polymorphism in intron 7 (rs761059)
      differed between AD cases and controls, with an adjusted odds ratio (OR) of 1.45
      (p=0.046, 95% CI: 1.01-2.08). One haplotype (ht2 CAGAG) was found in 14.0% of the
      AD patients and in 11.1% of the controls (p=0.04, OR=1.43. 95% CI; 1.01-2.01).
      Stratification by the ApoE-epsilon4 allele gave no significant difference between
      the groups. When the samples were stratified by gender, the genotypes of two SNPs
      (rs8052688, rs8063) were significantly associated with the risk of MCI among
      women. Our investigation suggests that UBE2I polymorphisms might be associated
      with a risk of AD and MCI.

PMID- 19765635
TI  - The effect of peripheral administration of growth hormone on AD-like cognitive
      deficiency in NBM-lesioned rats.
AB  - This study aimed to evaluate the peripheral administration of growth hormone (GH)
      on AD-like cognitive deficiency in NBM-lesioned rats induced by ibotenic acid (5
      microg/microl, in each side). Forty-eight male Wistar rats (20-24 months old;
      weighing 330+/-30 g) randomly divided into six groups (n=8). The groups include
      control group, which were intact rats; n-L+GH group: non-lesioned rats with GH
      treatment (1mg/kg, 9.00 am, for 10 consecutive days); n-L+Veh group: non-lesioned
      rats with vehicle treatment; L group: NBM-lesioned rats; L+GH group: NBM-lesioned
      rats with GH treatment and L+Veh group: NBM-lesioned rats with same volume of
      vehicle treatment. Peripheral administration of GH in control had no effect on
      learning and memory, while in L+GH group produced a significant enhancement in
      spatial learning and memory comparing to L and L+Veh groups. The percent of time
      spent in goal quarter during probe trial has decreased significantly in L and
      L+Veh groups compared to n-L groups. While it has increased significantly in L+GH
      group compared to L and L+Veh groups. No significant difference in percent of
      time spent was seen between the control and n-L groups. The GH has known as a
      mediate that effect through IGF-1. As the IGF-1 itself is earlier shown to
      improve cognitive function it is likely that the observed effect of GH is
      mediated through release of IGF-1 from peripheral tissue into the circulation for
      further transport across the BBB. This mechanism may result in the improvement of
      learning and memory in rats with NBM lesion.

PMID- 19765636
TI  - Effect of combined therapy with ephedrine and hyperbaric oxygen on neonatal
      hypoxic-ischemic brain injury.
AB  - Perinatal hypoxic-ischemic (HI) is a major cause of brain injury in the newborn,
      and there is a lack of effective therapies to reduce injury-related disorders.
      The aim of the present study was to evaluate the effect of a combination of
      ephedrine and hyperbaric oxygen (HBO) on neonatal hypoxic-ischemic brain injury.
      7-day-old Sprague-Dawley rat pups were randomly divided into sham operation, HI,
      ephedrine, HBO, and combined group. The ephedrine group was intraperitoneally
      injected with ephedrine, HBO group was treated for 2h at 2.5 absolute atmosphere
      (ATA) per day, the combined group received both ephedrine and HBO treatments, the
      sham operation and HI groups were intraperitoneally injected with normal saline.
      Rat brains at 7 days after HI, were collected to determine histopathological
      damage and the expression levels of Caspase-3 and Nogo-A. Four weeks after
      insult, animals were challenged with Morris water maze test. The expressions of
      Caspase-3 and Nogo-A were reduced in treating groups compared to those in HI
      group (P<0.01). Compared with the single treatment groups, the expression levels
      of Caspase-3 and Nogo-A were significantly reduced in the combined group
      (P<0.01). Compared with the single treatment groups, the average time of escape
      latency was significantly shorter (P<0.01) and the number of platform location
      crossing was more (P<0.05) in combined group. These findings indicate that the
      combination of ephedrine and HBO can enhance the neuroprotective effect in the
      neonatal rat HI model partially mediated by inhibiting Caspase-3 and Nogo-A
      pathways.

PMID- 19765637
TI  - Neuroprotective effects of bone morphogenetic protein 7 (BMP7) treatment after
      spinal cord injury.
AB  - Bone morphogenetic protein 7 (BMP7) has been shown to ameliorate reduced
      dendritic growth induced by glutamate excitotoxicity in neuronal tissue cultures
      and/or provide an enhancement of functional recovery in central nervous system
      (CNS) injury. BMP7 expression is modulated by spinal cord injury (SCI), but the
      molecular mechanisms involved in neuroprotection have not been clearly defined.
      Here, we show that BMP7 treatment of rats subjected to mild cervical SCI
      significantly increased the pro-survival mitogen-activated protein kinase-38
      (MAPK-38) pathway and levels of N-methyl-D-aspartate receptor 1 (NMDAR-1)
      resulting in a significant increase in neuronal sparing in the ventral horn of
      the spinal cord. Moreover, BMP7 was neuroprotective against glutamate-mediated
      excitotoxicity in cultured cortical neurons. These studies show that BMP7
      administration may be used as a therapeutic strategy to reduce the damaging
      excitotoxic effects following SCI.

PMID- 19765638
TI  - Colorectal distension-induced prefrontal cortex activation in the Wistar-Kyoto
      rat: implications for irritable bowel syndrome.
AB  - The prefrontal cortex plays a key role in the perception of painful stimuli,
      including those emerging from the viscera. Colorectal distension is a non
      invasive stimulus used to study visceral pain processing in the nervous system.
      Visceral hypersensitivity is one of the main characteristics of the functional
      bowel disorder irritable bowel syndrome (IBS). Moreover, recent human
      neuroimaging studies have emphasized the importance of altered brain activity and
      circuitry in the manifestation of IBS symptom severity and reaction to visceral
      stimuli. It is unclear whether animal models of visceral hypersensitivity display
      a similar response. Therefore, in the present study, we have used c-Fos protein
      immunoreactivity as an indicator of cell activation, to compare the response of
      the viscerally hypersensitive Wistar-Kyoto (WKY) rat and control Sprague-Dawley
      (SD) rat strains to colorectal distension (CRD), a noxious visceral stimulus.
      Several corticolimbic structures were analysed including the prelimbic cortex,
      infralimbic cortex and the rostral and caudal anterior cingulate cortices.
      Moreover, visceral hypersensitivity was also assessed behaviourally in both
      strains. As previously described WKY rats had a lower pain threshold than SD
      controls in response to CRD. In all brain regions analysed, exposure to CRD
      induced an increase in c-Fos activation in both the WKY and SD rats. However, an
      exaggerated cell activation was found in the prelimbic, infralimbic and rostral
      anterior cingulate cortices of the WKY rat compared to SD animals. No significant
      difference was found in caudal anterior cingulate cortex activation when the
      strains were compared. These results demonstrate, to our knowledge, for the first
      time an augmented colorectal distension-induced prefrontal cortex activity in WKY
      rats similar to that seen in IBS patients, further supporting the use of this
      strain as a model in which to study brain-gut axis dysregulation observed in IBS.

PMID- 19765639
TI  - The expression of nerve growth factor in mice lung following low-level toluene
      exposure.
AB  - To clarify the effect of indoor air pollutants on nerve growth factor (NGF)
      production in lung, male C3H/HeN mice were exposed to filtered air (control) or
      toluene at levels of 0.9 ppm, 9 ppm, or 90 ppm for 30 min via nose-only
      inhalation on days 0, 1, 2, 7, 14, 21, 28, 35, 42, 49 and 56. As an allergic
      mouse model, some mice (n=24) were immunized with ovalbumin. Lungs from each
      mouse were collected to determine NGF and related receptor expressions using real
      time reverse transcription polymerase chain reaction (RT-PCR) analysis. NGF and
      TrkA mRNAs were increased in the lungs of the immunized mice following exposure
      to 9 ppm toluene (n=6) (P<0.05 ppm vs. 0 ppm). Remarkably increased NGF-positive
      bronchiolus and alveolar epithelium cells were observed in 9 ppm toluene-exposed,
      immunized mice. To determine NGF mediating signaling, we also examined mRNA
      expression of neurotrophin receptor p75 (p75(NTR)) and oxidative stress marker,
      heme oxygenase (HO)-1 in the lung. There is no difference in the expressions of
      p75(NTR) and HO-1 between toluene-exposed and control mice. The expression of
      CCL2 and CCL3 mRNAs was significantly elevated in 9 ppm toluene-exposed,
      immunized mice. These findings suggest that the exposure with volatile organic
      compounds enhanced NGF expression and airway inflammation stronger in allergic
      individuals than in healthy individuals.

PMID- 19765640
TI  - Increase of ejaculatory capacity by systemic administration of the oquichpatli
      (Senecio cardiophyllus) aqueous crude extract in male rats.
AB  - AIM OF THE STUDY: To analyse the pro-ejaculatory properties of the proverbial
      Mexican plant oquichpatli, Senecio cardiophyllus, in an animal model for the
      study of ejaculation in spinal and anaesthetised male rats. MATERIALS AND
      METHODS: The aqueous crude extract of Senecio cardiophyllus (at 0.4, 1.2 and 4
      mg/kg) was i.v. administered to (a) anaesthetised and spinalised male rats after
      spinal cord transection and (b) anaesthetised and spinalised male rats previous
      to the inhibition of ejaculation elicited by repeated urethral stimulation. The
      motor pattern of ejaculation and the development of its inhibition were analysed
      under the influence of the aqueous crude extract of Senecio cardiophyllus and
      compared to urethrally induced ejaculations. RESULTS: Systemic administration of
      the Senecio cardiophyllus aqueous crude extract, at all tested doses, induced the
      ejaculatory response in male rats. This response was featured by a statistically
      significant augmented number of ejaculatory discharges when compared to control
      animals. Oquichpatli-induced ejaculatory responses included the expression of
      autonomic and motor components of ejaculation and the potent expulsion of
      urethral contents and seminal plugs. Administration of oquichpatli aqueous crude
      extract prevented the inhibition of ejaculation elicited by urethral stimulation
      by promoting a statistically significant increase in the expression of
      ejaculatory motor patterns. CONCLUSION: Present findings show by the first time
      that the aqueous crude extract of Senecio cardiophyllus possesses the ability to
      increase the ejaculatory capacity in male rats.

PMID- 19765641
TI  - In vitro profiling of endocrine disrupting effects of phenols.
AB  - Some phenols have been suspected to modulate the endocrine systems of wildlife
      and humans, but less is known about their interactions with different types of
      nuclear receptors. In this study, the ability of 2-tert-butylphenol, 2
      isopropylphenol, 4-tert-octylphenol (4-t-OP), 2,4-dichlorophenol (2,4-DCP), 3,4
      dichlorophenol (3,4-DCP), pentachlorophenol (PCP), bisphenols A (BPA),
      tetrabromobisphenol A (TBBPA), tetrachlorobisphenol A (TCBPA) and 4-phenylphenol
      to activate estrogen receptor (ER), androgen receptor (AR), progesterone receptor
      (PR) and estrogen-related receptor (ERR) were determined using a set of
      recombined yeast strains. It was found that 4-t-OP, 3,4-DCP, PCP, BPA, TBBPA,
      TCBPA and 4-phenylphenol were ERalpha agonists, while 4-t-OP, PCP and 4
      phenylphenol showed ERalpha antagonistic activities. 2-tert-Butylphenol, 4-t-OP,
      2-isopropylphenol, 2,4-DCP, 3,4-DCP, BPA, TCBPA and 4-phenylphenol were
      antagonists for AR, whereas none of the compounds studied were found to be an AR
      agonist. TCBPA, TBBPA and PCP were PR antagonists, and 2-tert-butylphenol, 3,4
      DCP, 4-t-OP, 4-phenylphenol and 2-isopropylphenol were weak inhibitors on
      expression under control of the PR. None of the phenols were PR agonists. 2-tert
      Butylphenol, 4-t-OP and PCP were ERRgamma inverse agonists, while 2,4-DCP, 3,4
      DCP, PCP, BPA, TBBPA and TCBPA exhibited the ability to reverse the ERR
      inhibition induced by 4-hydroxytamoxifen. Based on the functional agonistic or
      antagonistic receptor-mediated effects, we further discussed the possible action
      mechanisms of these phenols as endocrine disrupting chemicals.

PMID- 19765642
TI  - A tentative quantitative structure-toxicity relationship study of benzodiazepine
      drugs.
AB  - Benzodiazepines belong to a large family of drugs, being used as hypnotics,
      anxiolytics, tranquillizers, anticonvulsants, in pre-medication and intravenous
      sedation. Several quantitative structure-toxicity (lethal oral dose for mouse)
      relationship (QSTR) models for 54 benzodiazepine derivatives have been developed.
      The molecular structure of these compounds was energetically optimized by
      molecular mechanics calculations. To the lowest energy conformations thus
      obtained, quantum chemical calculations (RM1 approach) were applied to finally
      optimize the structures. Several structural descriptors, volumes, molecular
      surface area, hydrophobicities and quantum chemical descriptors were calculated
      from the minimized structures. Multiple linear regression (MLR) combined with
      genetic algorithm for variable selection, artificial neural networks (ANNs),
      support vector machines (SVMs) and partial least squares (PLS) have been
      employed. Few satisfactory MLR models with predictive power were obtained.
      Nonlinear modelling methods of ANNs and SVMs gave somewhat better models than
      those obtained by MLR using same set of descriptors. Additional information on
      the factors which influence the benzodiazepine toxicity was given by PLS. The
      obtained models can be used for a rough evaluation of benzodiazepine toxicity.

PMID- 19765643
TI  - Regulation of cytokine signaling and T-cell recruitment in the aging mouse brain
      in response to central inflammatory challenge.
AB  - Aging is often accompanied by increased levels of inflammatory molecules in the
      organism, but age-related changes in the brain response to inflammatory
      challenges still require clarification. We here investigated in mice whether
      cytokine signaling and T-cell neuroinvasion undergo age-related changes. We first
      analyzed the expression of molecules involved in T-cell infiltration and cytokine
      signaling regulation in the septum and hippocampus of 2-3 months and 20- to 24
      month-old mice at 4h after intracerebroventricular injections of tumor necrosis
      factor (TNF)-alpha or interferon-gammaversus saline injections. Transcripts of
      the chemokine CXCL9, intercellular adhesion molecule (ICAM)-1 and suppressor of
      cytokine signaling molecules (SOCS) 1 and 3 were increased in both age groups
      after cytokine injection; microglia-derived matrix metalloproteinase (MMP) 12
      mRNA was induced in old mice also after control saline injections. Age-related
      changes in ICAM-1 protein expression and T-cell infiltration were then analyzed
      in mice of 3-4, 8-9 and 15-16 months at 48h after TNF-alpha injections. ICAM-1
      immunoreactivity, and Western blotting in striatum, septum, hippocampus and
      hypothalamus showed progressive age-related enhancement of TNF-alpha-elicited
      ICAM-1 upregulation. Double immunofluorescence revealed ICAM-1 expression in
      microglia and astrocytic processes. CD3(+), CD4(+) and CD8(+) T-cells exhibited
      progressive age-related increases in brain parenchyma and choroid plexus after
      cytokine exposure. The findings indicate that the brain responses to inflammatory
      challenges are not only preserved with advancing age, but also include gradual
      amplification of ICAM-1 expression and T-cell recruitment. The data highlight
      molecular and cellular correlates of age-related increase of brain sensitivity to
      inflammatory stimuli, which could be involved in altered brain vulnerability
      during aging.

PMID- 19765644
TI  - Short-term stress enhances cellular immunity and increases early resistance to
      squamous cell carcinoma.
AB  - In contrast to chronic/long-term stress that suppresses/dysregulates immune
      function, an acute/short-term fight-or-flight stress response experienced during
      immune activation can enhance innate and adaptive immunity. Moderate ultraviolet
      B (UV) exposure provides a non-invasive system for studying the naturalistic
      emergence, progression and regression of squamous cell carcinoma (SCC). Because
      SCC is an immunoresponsive cancer, we hypothesized that short-term stress
      experienced before UV exposure would enhance protective immunity and increase
      resistance to SCC. Control and short-term stress groups were treated identically
      except that the short-term stress group was restrained (2.5h) before each of nine
      UV-exposure sessions (minimum erythemal dose, 3-times/week) during weeks 4-6 of
      the 10-week UV exposure protocol. Tumors were measured weekly, and tissue
      collected at weeks 7, 20, and 32. Chemokine and cytokine gene expression was
      quantified by real-time PCR, and CD4+ and CD8+ T cells by flow cytometry and
      immunohistochemistry. Compared to controls, the short-term stress group showed
      greater cutaneous T-cell attracting chemokine (CTACK)/CCL27, RANTES, IL-12, and
      IFN-gamma gene expression at weeks 7, 20, and 32, higher skin infiltrating T cell
      numbers (weeks 7 and 20), lower tumor incidence (weeks 11-20) and fewer tumors
      (weeks 11-26). These results suggest that activation of short-term stress
      physiology increased chemokine expression and T cell trafficking and/or function
      during/following UV exposure, and enhanced Type 1 cytokine-driven cell-mediated
      immunity that is crucial for resistance to SCC. Therefore, the physiological
      fight-or-flight stress response and its adjuvant-like immuno-enhancing effects,
      may provide a novel and important mechanism for enhancing immune system mediated
      tumor-detection/elimination that merits further investigation.

PMID- 19765645
TI  - Critical methods in Free Radical Biology & Medicine.

PMID- 19765646
TI  - Peroxisome dynamics in Arabidopsis plants under oxidative stress induced by
      cadmium.
AB  - Peroxisomes are organelles with an essentially oxidative metabolism that are
      involved in various metabolic pathways such as fatty acid beta-oxidation,
      photorespiration, and metabolism of reactive oxygen species (ROS) and reactive
      nitrogen species. These organelles are highly dynamic but there is little
      information about the regulation of, and the effects of environment on,
      peroxisome movement. In this work a stable Arabidopsis line expressing the GFP
      SKL peptide targeted to peroxisomes was characterized. Peroxisome-associated
      fluorescence was observed in all tissues, including leaves (mesophyll and
      epidermal cells, trichomes, and stomata) and roots. The dynamics of peroxisomes
      in epidermal cells was examined by confocal laser microscope, and various types
      of movement were observed. The speed of movement differed depending on the plant
      age. Treatment of plants with CdCl(2) (100 microM) produced a significant
      increase in speed, which was dependent on endogenous ROS and Ca(2+), but was not
      related to actin cytoskeleton modifications. In light of the results obtained, it
      is proposed that the increase in peroxisomal motility observed in Arabidopsis
      plants could be a cellular mechanism of protection against the Cd-imposed
      oxidative stress. Other possible roles for the enhanced peroxisome movement in
      plant cell physiology are discussed.

PMID- 19765647
TI  - Morphological and proliferative abnormalities in renal mesangial cells lacking
      RhoGDI.
AB  - The regulation of Rho GTPase activities and expression is critical in the
      development and function of the kidney. Rho GTPase activities and cytosol
      membrane cycling are regulated by Rho GDP Dissociation Inhibitor (RhoGDI), and
      RhoGDI knockout mice develop defects in kidney structure and function that lead
      to death due to renal failure. It is therefore important to understand the
      changes in RhoGDI-regulated Rho GTPase activities and cell morphology that lead
      to kidney failure in RhoGDI (-/-) mice. Here, we characterize a renal mesangial
      cell line derived from the RhoGDI (-/-) mouse in which we verify the absence of
      GDI proteins. In the absence of RhoGDI, we show an increase in the specific
      activity of Rac1, and to a lesser extent, RhoA and Cdc42 GTPases in these cells.
      This is accompanied by a compensatory decrease in the steady-state protein levels
      of Rho GTPases. Morphological analysis of RhoGDI (-/-) mesangial cells reveals a
      decrease in cell spreading and in focal contacts compared to wild-type cells.
      Finally, RhoGDI (-/-) mesangial cells show a decreased ability to proliferate and
      survive. These functional and structural changes are likely to contribute to the
      defects in renal architecture and function observed in the RhoGDI (-/-) mouse.

PMID- 19765648
TI  - Differential regulation of NHE1 phosphorylation and glucose uptake by inhibitors
      of the ERK pathway and p90RSK in 3T3-L1 adipocytes.
AB  - Insulin stimulates trafficking of GLUT4 to the cell surface for glucose uptake
      into target cells, and phosphorylation of Ser703 of the Na+/H+ exchanger NHE1,
      which activates proton efflux. The latter has been proposed to facilitate optimal
      glucose uptake into cardiomyocytes. We found that the insulin-stimulated
      phosphorylation of Ser703 of NHE1 is mediated by p90RSK but not directly coupled
      to glucose uptake in 3T3-L1 adipocytes in the short-term. Inhibiting Erk1/2
      activation prevented NHE1 phosphorylation but not glucose uptake in 3T3-L1
      adipocytes. In contrast, both NHE1 phosphorylation and insulin-stimulated uptake
      of glucose into 3T3-L1 adipocytes were blocked by inhibitors of the N-terminal
      kinase domain of p90RSK, namely BI-D1870 and SL0101, but not the FMK inhibitor of
      the C-terminal kinase domain of p90RSK, though in our hands FMK did not inhibit
      p90RSK in 3T3-L1 adipocytes. Further experiments were consistent with
      phosphorylation of AS160 by PKB/Akt mediating insulin-stimulated trafficking of
      GLUT4 to the plasma membrane. BI-D1870 and SL0101 however, inhibited glucose
      uptake without blocking GLUT4 translocation. While BI-D1870 partially inhibited
      insulin-stimulated PKB activation in these cells, this only partially inhibited
      AS160 phosphorylation and did not block GLUT4 trafficking, suggesting that p90RSK
      might regulate glucose transport after GLUT4 translocation. Moreover, BI-D1870
      also prevented PMA-induced glucose transport in 3T3-L1 adipocytes further
      suggesting a role for p90RSK in regulating uptake of glucose into the cells.
      Kinetic experiments are consistent with SL0101 being a direct competitor of 2
      deoxyglucose entry into cells, and this compound might also inhibit uptake of
      glucose into cells via inhibiting p90RSK, as revealed by comparison with the
      inactive form of the inhibitor. Taken together, we propose that BI-D1870 and
      SL0101 might exert their inhibitory effects on glucose uptake in 3T3-L1
      adipocytes at least partially through a p90RSK dependent step after GLUT4 becomes
      associated with the plasma membrane.

PMID- 19765649
TI  - Resveratrol ameliorates high glucose-induced protein synthesis in glomerular
      epithelial cells.
AB  - High glucose-induced protein synthesis in the glomerular epithelial cell (GEC) is
      partly dependent on reduction in phosphorylation of AMP-activated protein kinase
      (AMPK). We evaluated the effect of resveratrol, a phytophenol known to stimulate
      AMPK, on protein synthesis. Resveratrol completely inhibited high glucose
      stimulation of protein synthesis and synthesis of fibronectin, an important
      matrix protein, at 3 days. Resveratrol dose-dependently increased AMPK
      phosphorylation and abolished high glucose-induced reduction in its
      phosphorylation. We examined the effect of resveratrol on critical steps in mRNA
      translation, a critical event in protein synthesis. Resveratrol inhibited high
      glucose-induced changes in association of eIF4E with eIF4G, phosphorylation of
      eIF4E, eEF2, eEF2 kinase and, p70S6 kinase, indicating that it affects important
      events in both initiation and elongation phases of mRNA translation. Upstream
      regulators of AMPK in high glucose-treated GEC were explored. High glucose
      augmented acetylation of LKB1, the upstream kinase for AMPK, and inhibited its
      activity. Resveratrol prevented acetylation of LKB1 and restored its activity in
      high glucose-treated cells; this action did not appear to depend on SIRT1, a
      class III histone deacetylase. Our data show that resveratrol ameliorates protein
      synthesis by regulating the LKB1-AMPK axis.

PMID- 19765650
TI  - Expression and significance of HERG (KCNH2) potassium channels in the regulation
      of MDA-MB-435S melanoma cell proliferation and migration.
AB  - The human ether-a-go-go related gene (HERG) potassium channel has elicited
      intense scientific interest due to its role in cardiac repolarization and its
      association with arrhythmia and sudden cardiac death. Increasing evidence
      indicates the involvement of HERG channels in the pathophysiology of cancer. In
      the present study we investigated the expression of HERG protein in MDA-MB-435S
      melanoma cells, and its importance in regulating cell proliferation and
      migration. Our results showed that HERG was expressed on protein and mRNA levels
      in MDA-MB-435S melanoma cells. In these cells blockade of HERG channels with the
      HERG blockers E 4301 or cisapride attenuated both proliferation and migration of
      the cells. Activation of HERG with PD118057 stimulated cell migration.
      Furthermore, HERG small interfering (si) RNA attenuated the proliferation and
      migration of the cells. Incubation of MDA-MB-435S cells with E 4301 decreased the
      phosphorylation of mitogen-activated protein (MAP) kinase and the expression of
      the c-fos transcription factor. In control experiments, overexpression of HERG
      channels in HEK-293 cells dramatically increased the proliferation and migration
      of the cells and blocking HERG in these cells attenuated both proliferation and
      migration. Our results indicate that MDA-MB-435S cells express HERG channels and
      blockade of HERG results in the attenuation of both proliferation and migration
      by a mechanism dependent, at least in part, on an inhibition of the MAP kinase/c
      fos pathway.

PMID- 19765651
TI  - Proteolysis of sigmaS (RpoS) and the general stress response in Escherichia coli.
AB  - The sigma(S) (RpoS) subunit of RNA polymerase is the master regulator of the
      general stress response in Escherichia coli. Regulation of sigma(S) occurs at the
      levels of transcription, translation, proteolysis and protein activity. As
      sigma(S) has become a paradigm for regulated proteolysis in bacteria, this review
      summarizes our current knowledge about the molecular mechanisms and multiple
      signal integration in sigma(S) degradation.

PMID- 19765652
TI  - Combined hydroxypropyl-beta-cyclodextrin and poly(anhydride) nanoparticles
      improve the oral permeability of paclitaxel.
AB  - The aim of this work was to study the effect of the combination between 2
      hydroxypropyl-beta-cyclodextrin (HPCD) and bioadhesive nanoparticles on the
      encapsulation and intestinal permeability of paclitaxel (PTX). In this context, a
      solid inclusion complex between PTX and HPCD was prepared by an evaporation
      method. Then, the complex was incorporated in poly(anhydride) nanoparticles by a
      solvent displacement method. The resulting nanoparticles, PTX-HPCD NP, displayed
      a size of about 300 nm and a drug loading of about 170 microg/mg (500-fold higher
      than in the absence of HPCD). The effect of these nanoparticles on the
      permeability of intestinal epithelium was investigated using the Ussing chamber
      technique. The apparent permeability (P(app)) of PTX was found to be 12-fold
      higher when formulated as PTX-HPCD NP than when formulated as Taxol (control).
      Furthermore, when interaction between nanoparticles and the mucosa was avoided,
      the permeability of PTX significantly decreased. In summary, the association
      between PTX-HPCD and poly(anhydride) nanoparticles would induce a positive effect
      over the intestinal permeability of paclitaxel, being the bioadhesion a mandatory
      condition in this phenomena.

PMID- 19765653
TI  - Pharmacokinetic-pharmacodynamic modeling of the effect of propofol on alpha 1
      adrenoceptor-mediated positive inotropy in rat heart.
AB  - Since it is unclear whether and how propofol affects the alpha(1)-mediated
      inotropic response, we used a pharmacokinetic-pharmacodynamic modeling approach
      in isolated rat hearts to analyze the effect of propofol on receptor binding and
      signal transduction. In Langendorff rat hearts perfused with buffer containing
      12.3 microM phenylephrine, 1.27 nmol doses of [(3)H]-prazosin were infused (over
      1 min), in the absence and presence of propofol (28 microM). Simultaneous
      analysis of prazosin outflow concentration and inotropic response (left
      ventricular developed pressure) using an agonist-antagonist interaction model
      allowed to estimate receptor affinity, as well as the parameters of the
      operational model of agonism. Propofol significantly (P<0.05) increased the
      negative inotropic effect of prazosin. Modeling suggested that propofol increased
      the Hill coefficient, which determines the steepness of the stimulus-response
      curve for the positive inotropic effect of phenylephrine, from 1 to 2.6+/-0.1 and
      decreased the maximum achievable inotropic effect from 121.2+/-12 to 91.8+/-6
      mmHg. Thus, propofol may attenuate the positive inotropic effect of alpha(1)
      agonists by decreasing the transduction efficiency of alpha(1)-adrenergic
      receptor signaling primarily at lower receptor occupancy.

PMID- 19765654
TI  - Triple verses glimepiride plus metformin therapy on cardiovascular risk
      biomarkers and diabetic cardiomyopathy in insulin resistance type 2 diabetes
      mellitus rats.
AB  - IRtype2DM patients are often treated with a combination of antidiabetic agents.
      Drugs with different complementary mechanisms of action frequently used in daily
      clinical practice but glycemic control with monotherapeutic attempts fail in the
      long run. To date, biomarkers for cardiovascular risk and insulin sensitivity
      with combination of triple oral hypoglycemic therapies are not fully revelled in
      view of additional cardiovascular risk reduction. In the present study, IRtype2DM
      induced by administering streptozotocin (90 mg/kg, i.p.) in neonatal rat model.
      IRtype2DM rats were selected by determining FPI [>60 pmol/l]; HOMA-IR &
      Hyperinsulinemic euglycemic clamp technique at 6 weeks and then treated for 8
      weeks with (i) Metformin (120 mg/kg, o.d.)+Glimepiride (1mg/kg, o.d.), (ii)
      Metformin (265 mg/kg, o.d.)+Rosiglitazone (1mg/kg, o.d.)+Glimepiride (0.7 mg/kg,
      o.d.). At the end cardiovascular risk parameters evaluated by ELISA kits and
      insulin sensitivity were determined by HOMA-IR. In conclusion, triple oral
      hypoglycemic therapy improves glycemic control, insulin sensitivity, retards
      diabetic cardiomyopathy and does not increased body weight; decrease more
      detrimental inflammatory markers, increase interleukin-10 and adiponectin in
      neonatal streptozotocin-induced IRtype2DM Wistar Albino Rats. Triple therapy
      showed a synergistic effect and was promising in insulin resistance, better in
      additional cardiovascular risk reduction and those nonresponders to metformin add
      on glimepiride therapy.

PMID- 19765655
TI  - Comparison of the dissolution and pharmacokinetic profiles of two galenical
      formulations of the endothelin receptor antagonist macitentan.
AB  - Macitentan (ACT-064992) is an orally active endothelin receptor antagonist. We
      first compared the in vitro dissolution characteristics of uncoated and film
      coated tablets with hard gelatin capsules containing 10mg ACT-064992.
      Subsequently, we compared the oral pharmacokinetics of ACT-064992 and its active
      metabolite ACT-132577 of the coated tablet and the gelatin capsule formulation in
      11 male volunteers. The dissolution profile showed a rapid disintegration of all
      formulations with >90% dissolution of ACT-064992 within 45 min. The
      pharmacokinetics of ACT-064992 and its metabolite ACT-132577 were comparable for
      the two formulations. ACT-064992 revealed a slow absorption (median t(max) 8h)
      and a terminal half-life of approximately 13 h. Bioequivalence criteria were met
      for AUC(0-t) and AUC(0-infinity). Mean C(max) was 19% lower after ingestion of
      the tablet compared to capsules with its lower 90% confidence limit below the
      accepted bioequivalence range. The pharmacokinetics of the metabolite ACT-132577,
      characterized by a t(max) of approximately 48 h and a terminal half-life of
      approximately 45 h, was not different between the two formulations. We conclude
      that the absorption profile of the tablet differs from the capsule in peak but
      not in total exposure, which is not expected to be of clinical significance.

PMID- 19765656
TI  - Adult human bone marrow stromal cells regulate expression of their MMPs and TIMPs
      in differentiation type-specific manner.
AB  - Previously, we described a profound impact of structural conformation of collagen
      matrix on osteogenic and adipogenic differentiation of bone marrow stromal cells.
      Thus, a marginal p38-independent adipogenesis on native collagen I matrix
      contrasts with an efficient p38-dependent differentiation on denatured collagen
      I. An efficient Hsp90-dependent osteogenesis occurs on native collagen I matrix
      but not on its denatured counterpart where it is insignificant and proceeds in an
      Hsp90-independent manner. Whereas only marginal osteogenesis and no detectable
      adipogenesis of bone marrow stromal cells occur on native collagen IV, the same
      matrix supports a highly efficient adipogenesis in denatured structural state.
      The present study addresses the opposite direction in the flow of cell-matrix
      interaction, namely the cells' influence on structural state of collagen matrix,
      and tests the possibility that differentiating bone marrow stromal cells may
      adjust the expression phenotype of MMP and TIMP in such a way that, if translated
      into matrix modification, would facilitate the maintenance of collagen matrix in
      or its modification into structural state optimal for the ongoing differentiation
      process. The results obtained indicate that this is indeed the case. In bone
      marrow stromal cells stimulated to undergo adipogenesis the expression of MMP
      increases and that of TIMP decreases. In cells induced to undergo osteogenesis
      the opposite is true: MMP/TIMP expression is adjusted in a manner that, if
      translated into matrix modification, could promote the native structural
      conformation optimal for this type of differentiation. The results obtained also
      indicate that the observed adjustment in MMP/TIMP expression phenotype might be
      an early differentiation event and that differentiation stimulation alone might
      be sufficient to trigger it even on matrices not favorable to a given type of
      differentiation. The findings of the present study raise significant questions
      and indicate directions for further experimentation.

PMID- 19765657
TI  - Competition and co-existence of Zoophthora radicans and Pandora blunckii, two co
      occurring fungal pathogens of the diamondback moth, Plutella xylostella.
AB  - The entomopathogenic fungi Zoophthora radicans and Pandora blunckii co-occur in
      field populations of Plutella xylostella and, therefore, are likely to interact
      during the infection process. We have investigated the possible outcomes of these
      interactions in the laboratory. Using four isolates, two of each fungal species,
      inter-specific interaction experiments were done in Petri dishes and on intact
      plants. In Petri dish experiments, larvae were inoculated directly using
      sporulating mats of mycelium, both species had the same opportunity to infect and
      only the relative concentration of conidia of each pathogen species applied was
      manipulated. In the intact plant experiments, larvae were placed onto fungus
      contaminated plants, inoculation was passive and the probability of infection by
      either or both species of fungi depended on larval activity and proximity to
      inoculum. In the Petri dish experiment, the species with the largest
      concentration of conidia out-competed the other regardless of virulence, and
      results were similar in the intact plant experiment. The ecological implications
      for competition or co-existence of these two pathogens in the field are
      discussed.

PMID- 19765658
TI  - Trichoderma species form endophytic associations within Theobroma cacao
      trichomes.
AB  - Trichoderma species are usually considered soil organisms that colonize plant
      roots, sometimes forming a symbiotic relationship. Recent studies demonstrate
      that Trichoderma species are also capable of colonizing the above ground tissues
      of Theobroma cacao (cacao) in what has been characterized as an endophytic
      relationship. Trichoderma species can be re-isolated from surface sterilized
      cacao stem tissue, including the bark and xylem, the apical meristem, and to a
      lesser degree from leaves. SEM analysis of cacao stems colonized by strains of
      four Trichoderma species (Trichoderma ovalisporum-DIS 70a, Trichoderma hamatum
      DIS 219b, Trichoderma koningiopsis-DIS 172ai, or Trichoderma harzianum-DIS 219f)
      showed a preference for surface colonization of glandular trichomes versus non
      glandular trichomes. The Trichoderma strains colonized the glandular trichome
      tips and formed swellings resembling appresoria. Hyphae were observed emerging
      from the glandular trichomes on surface sterilized stems from cacao seedlings
      that had been inoculated with each of the four Trichoderma strains. Fungal hyphae
      were observed under the microscope emerging from the trichomes as soon as 6h
      after their isolation from surface sterilized cacao seedling stems. Hyphae were
      also observed, in some cases, emerging from stalk cells opposite the trichome
      head. Repeated single trichome/hyphae isolations verified that the emerging
      hyphae were the Trichoderma strains with which the cacao seedlings had been
      inoculated. Strains of four Trichoderma species were able to enter glandular
      trichomes during the colonization of cacao stems where they survived surface
      sterilization and could be re-isolated. The penetration of cacao trichomes may
      provide the entry point for Trichoderma species into the cacao stem allowing
      systemic colonization of this tissue.

PMID- 19765659
TI  - Wnt signaling in development and disease.
AB  - The Wnt signaling pathway is one of the central morphogenic signaling pathways
      regulating early vertebrate development. In recent years, it has become clear
      that the Wnt pathway also regulates many aspects of nervous system development
      from the patterning stage through the regulation of neural plasticity. In this
      review, we first present an overview of the components of the Wnt signaling
      pathway and then go on to discuss the literature describing the multitude of
      roles of Wnts in nervous system. In the latter portion of the review, we turn to
      the ways that defects in Wnt signaling lead to neurologic disease.

PMID- 19765660
TI  - Voltage-gated sodium channel expression in rat spiral ganglion neurons.
AB  - The spiral ganglion neurons (SGN) provide the afferent innervation of the hair
      cells in the organ of Corti and relay auditory information from the inner ear to
      the brain. Voltage-gated sodium channels (Na(V)) initiate and propagate action
      potentials that encode this sensory information but little is known regarding the
      subtypes expressed in these cells. We have used RT-PCR and immunohistochemistry
      to study the compliment and anatomical distribution of Na(V) channels in rodent
      SGN. Na(V)1.1, Na(V)1.6 and Na(V)1.7 were all detected at the mRNA level.
      Fluorescence or streptavidin-horseradish peroxidase immunohistochemistry extended
      these findings, demonstrating predominant localisation of Na(V)1.6 and Na(V)1.7
      on SGN cell bodies and Na(V)1.1 on axonal processes. Dual labelling with
      peripherin demonstrated higher Na(V)1.6 and Na(V)1.7 expression on Type I rather
      than Type II neurons. These results provide evidence for selective expression and
      variations in the distribution of VGSC in the rodent SGN, which may guide further
      studies into afferent function in the auditory pathway and therapeutic approaches
      for diseases such as hearing loss and tinnitus.

PMID- 19765661
TI  - Thyroxin regulates BDNF expression to promote survival of injured neurons.
AB  - A growing amount of evidence indicates that neuronal trauma can induce a
      recapitulation of developmental-like mechanisms for neuronal survival and
      regeneration. Concurrently, ontogenic dependency of central neurons for brain
      derived neurotrophic factor (BDNF) is lost during maturation but is re-acquired
      after injury. Here we show in organotypic hippocampal slices that thyroxin, the
      thyroid hormone essential for normal CNS development, induces up-regulation of
      BDNF upon injury. This change in the effect of thyroxin is crucial to promote
      survival and regeneration of damaged central neurons. In addition, the effect of
      thyroxin on the expression of the K-Cl cotransporter (KCC2), a marker of neuronal
      maturation, is changed from down to up-regulation. Notably, previous results in
      humans have shown that during the first few days after traumatic brain injury or
      spinal cord injury, thyroid hormone levels are often diminished. Our data suggest
      that maintaining normal levels of thyroxin during the early post-traumatic phase
      of CNS injury could have a therapeutically positive effect.

PMID- 19765662
TI  - Evolutionary diversification of the gall midge genus Asteromyia (Cecidomyiidae)
      in a multitrophic ecological context.
AB  - Gall-forming insects provide ideal systems to analyze the evolution of host
      parasite interactions and understand the ecological interactions that contribute
      to evolutionary diversification. Flies in the family Cecidomyiidae represent the
      largest radiation of gall-forming insects and are characterized by complex
      trophic interactions with plants, fungal symbionts, and predators. We analyzed
      the phylogenetic history and evolutionary associations of the North American
      cecidomyiid genus Asteromyia, which is engaged in a complex and perhaps co
      evolving community of interactions with host-plants, fungi, and parasitoids.
      Mitochondrial gene trees generally support current classifications, but reveal
      extensive cryptic diversity within the eight named species. Asteromyia likely
      radiated after their associated host-plants in the Astereae, but species groups
      exhibit strong associations with specific lineages of Astereae. Evolutionary
      associations with fungal mutualists are dynamic, however, and suggest rapid and
      perhaps coordinated changes across trophic levels.

PMID- 19765663
TI  - Phylogeography of the ocellated skink Chalcides ocellatus (Squamata, Scincidae),
      with the use of mtDNA sequences: a hitch-hiker's guide to the Mediterranean.
AB  - We analyze geographic genetic variation in C. ocellatus to evaluate the
      influences of major climatic, paleogeographic and anthropogenic factors in its
      biogeographic history. Ninety four specimens from 61 populations were collected
      across all of its geographical range and analyzed based on partial mitochondrial
      sequences (cyt b, 12S, and ND1). Our results demonstrate that an ancestral form
      of C. ocellatus, which expanded in northwestern Africa at the end of Miocene,
      diverged in at least three separate evolutionary lineages approximately 4.57Ma:
      C. humilis spread south of the Sahara, while the other two (C. ocellatus sensu
      stricto) were restricted in the coastal North African region. The complicated
      history of the ocellated skink is a result of multiple vicariant phenomena
      followed by multiple active or passive dispersals. The Messinian salinity crisis
      and the re-flooding of the Mediterranean basin, the climatic transition from
      Middle to Upper Pliocene, and the hyperarid phase of the Sahara, affected the
      distribution and diversification of C. ocellatus, while in historical times it
      was introduced in the central Mediterranean islands and eastern Mediterranean
      region from Tunisia and Cyrenaica, respectively.

PMID- 19765664
TI  - Scratching the niche that controls Caenorhabditis elegans germline stem cells.
AB  - The Caenorhabditis elegans gonad provides a well-defined model for a stem cell
      niche and its control of self-renewal and differentiation. The distal tip cell
      (DTC) forms a mesenchymal niche that controls germline stem cells (GSCs), both to
      generate the germline tissue during development and to maintain it during
      adulthood. The DTC uses GLP-1/Notch signaling to regulate GSCs; germ cells
      respond to Notch signaling with a network of RNA regulators to control the
      decision between self-renewal and entry into the meiotic cell cycle.

PMID- 19765665
TI  - The stem cell--chromatin connection.
AB  - Stem cells self-renew and give rise to all differentiated cell types of the adult
      body. They are classified as toti-, pluri- or multi-potent based on the number of
      different cell types they can give rise to. Recently it has become apparent that
      chromatin regulation plays a critical role in determining the fate of stem cells
      and their descendants. In this review we will discuss the role of chromatin
      regulators in maintenance of stem cells and their ability to give rise to
      differentiating cells in both the animal and plant kingdom. We will highlight
      similarities and differences in chromatin-mediated control of stem cell fate in
      plants and animals. We will consider possible reasons why chromatin regulators
      play a central role in pluripotency in both kingdoms given that multicellularity
      evolved independently in each.

PMID- 19765666
TI  - Hormonal input in plant meristems: A balancing act.
AB  - Plant hormones are a group of chemically diverse molecules that control virtually
      all aspects of plant development. Classical plant hormones were identified many
      decades ago in physiology studies that addressed plant growth regulation. In
      recent years, biochemical and genetic approaches led to the identification of
      many molecular components that mediate hormone activity, such as hormone
      receptors and hormone-regulated genes. This has greatly contributed to the
      understanding of the mechanisms underlying hormone activity and highlighted the
      intricate crosstalk and integration of hormone signalling and developmental
      pathways. Here we review and discuss recent findings on how hormones regulate the
      activity of shoot and root apical meristems.

PMID- 19765667
TI  - Endocannabinoid 1 and 2 (CB(1); CB(2)) receptor agonists affect negatively cow
      luteal function in vitro.
AB  - Thirty to 40% of pregnancies are lost during the first third of pregnancy, which
      has been hypothesized to be due to inadequate progesterone secretion by the
      corpus luteum. Loss of luteal progesterone secretion during the estrous cycle is
      via uterine secretion of prostaglandin F(2)alpha (PGF(2)alpha). Cow luteal tissue
      secretion of prostaglandins (PG) E (PGE(1)+PGE(2)) and PGF(2)alpha are derived
      from precursors in membrane phospholipids. Cow luteal tissue secretion of PGE and
      PGF(2)alpha increased linearly with time in culture with the PGE: ratio being
      1:1. PGE(1) or PGE(2) are luteotropic in cows and ewes and antiluteolytic in
      vitro and in vivo in ewes. Endocannabinoids are also derived from phospholipids
      and are associated with infertility, presumably by reducing implantation;
      however, effects of endocannabinoids on luteal function have not been addressed.
      The objective of this experiment was to determine the effects of endocannabinoid
      type 1 and 2 receptor agonists and receptor antagonists or a fatty acid amide
      hydrolase (FAAH; catabolizes endocannabinoids) inhibitor, PGE(1), or PGF(2)alpha
      on bovine luteal secretion of progesterone, PGE, and PGF(2)alphain vitro. PGE and
      PGF(2)alpha was increased (P< or =0.05) with time in culture, while progesterone
      did not change (P> or =0.05) with time in vehicle-treated luteal slices in vitro.
      Progesterone was increased (P< or =0.05) by PGE(1) and decreased (P< or =0.05) by
      PGF(2)alpha, CB(1) or CB(2) receptor agonists, or a FAAH inhibitor. Both PGE and
      PGF(2)alpha were decreased (P< or =0.05) by CB(1) or CB(2) receptor agonists or a
      FAAH inhibitor when compared to vehicle controls. It is concluded that
      endocannabinoid receptor agonists negatively affect cow luteal function in vitro
      and that the corpus luteum may also be a site for endocannabinoid decreased
      fertility as well as a reduction in implantation.

PMID- 19765668
TI  - Uterine autonomic nerve innervation plays a crucial role in regulating rat
      uterine mast cell functions during embryo implantation.
AB  - To explore the potential mechanism of how uterine innervations would affect the
      uterine mast cell (MC) population and functions during the periimplantation. We
      herein first examined the consequence of uterine neurectomy on embryo
      implantation events. We observed that amputation of autonomic nerves innervating
      the uterus led to on-time implantation failure in rats. Exploiting MC culture and
      ELISA approaches, we then further analyzed the effect of neurectomy on cellular
      histamine levels and its release from uterine MCs, to elucidate the relation of
      the autonomic nerves and local cellular immunity in the uterine during early
      pregnancy. We observed that disconnection of autonomic nerve innervation
      significantly increased the population of uterine MCs. Most interestingly, these
      increased number of uterine MCs in neuroectomized rats contained a much reduced
      cellular level of histamine. Our subsequent challenge experiments revealed that
      uterine MCs in nerve amputated rats exhibited enhanced histamine releasing rate
      in response to substance P and antiIgE, suggesting loss of nerve innervation in
      the uterus not only increases the population of uterine MCs, but also facilitates
      the release of histamine from MCs, thus subsequently interfere with the normal
      implantation process. Collectively, our findings provide a new line of evidence
      supporting the concept that immune-neuro-endocrine network plays important role
      during pregnancy establishment and maintenance.

PMID- 19765669
TI  - A systemically administered EP2 receptor agonist stimulates pulmonary
      angiogenesis in a murine model of emphysema.
AB  - We investigated whether systemically administered EP2 receptor agonists would
      stimulate angiogenesis in the emphysematous lungs of mice. Saline or porcine
      pancreatic elastase was intratracheally administered to C57BL/6J mice to induce
      the formation of emphysematous lesions, and 4 weeks later the mice were
      intraperitoneally injected with an EP2 receptor agonist, ONO-AE1-259 or PGE2, or
      saline on days 1-5 each week for 3 weeks. Intraperitoneal ONO-AE1-259 in the mice
      in the intratracheal saline group increased pulmonary capillary volume to 114.9%
      of the control value (P<0.05), and when administered to the intratracheal
      elastase group, ONO-AE1-259 partially restored pulmonary capillary volume, from
      70.9% of the control value to 88.3% of the control value (P<0.05).
      Intraperitoneal PGE2 tended to increase pulmonary capillary volume in the mice in
      the intratracheal saline group (P=0.07) but not in the intratracheal elastase
      group. Intraperitoneal ONO-AE1-259 and PGE2 each increased the concentration of
      vascular endothelial growth factor (VEGF) and the number of endothelial
      progenitor cells (EPCs) in circulating blood. These results suggest that
      systemically administered ONO-AE1-259 stimulates pulmonary angiogenesis in an
      elastase-induced murine model of emphysema.

PMID- 19765670
TI  - Reduction of use of animals in regulatory genotoxicity testing: Identification
      and implementation opportunities-Report from an ECVAM workshop.
AB  - In vivo genetic toxicology tests measure direct DNA damage or the formation of
      gene or chromosomal mutations, and are used to predict the mutagenic and
      carcinogenic potential of compounds for regulatory purposes and/or to follow-up
      positive results from in vitro testing. These tests are widely used and consume
      large numbers of animals, with a foreseeable marked increase as a result of the
      EU chemicals legislation (REACH), which may require follow-up of any positive
      outcome in the in vitro standard battery with appropriate in vivo tests,
      regardless of the tonnage level of the chemical. A 2-day workshop with
      genotoxicity experts from academia, regulatory agencies and industry was hosted
      by the European Centre for the Validation of Alternative Methods (ECVAM) in
      Ranco, Italy from 24 to 25 June 2008. The objectives of the workshop were to
      discuss how to reduce the number of animals in standard genotoxicity tests,
      whether the application of smarter test strategies can lead to lower animal
      numbers, and how the possibilities for reduction can be promoted and implemented.
      The workshop agreed that there are many reduction options available that are
      scientifically credible and therefore ready for use. Most of these are compliant
      with regulatory guidelines, i.e. the use of one sex only, one administration and
      two sampling times versus two or three administrations and one sampling time for
      micronucleus (MN), chromosomal aberration (CA) and Comet assays; and the
      integration of the MN endpoint into repeat-dose toxicity studies. The omission of
      a concurrent positive control in routine CA and MN tests has been proven to be
      scientifically acceptable, although the OECD guidelines still require this; also
      the combination of acute MN and Comet assay studies are compliant with
      guidelines, except for sampling times. Based on the data presented at the
      workshop, the participants concluded that these options have not been
      sufficiently utilized to date. Key factors for this seem to be the uncertainty
      regarding regulatory compliance/acceptance, lack of awareness, and an in many
      cases unjustified uncertainty regarding the scientific acceptance of reduction
      options. The workshop therefore encourages the use and promotion of these options
      as well as the dissemination of data related to reduction opportunities by the
      scientific community in order to boost the acceptance level of these approaches.
      Furthermore, experimental proof is needed and under way to demonstrate the
      credibility of additional options for reduction of the number of animals, such as
      the integration of the Comet assay into repeat-dose toxicity studies.

PMID- 19765671
TI  - Image of the month. Hepatocellular carcinoma mimicking bile duct stone.

PMID- 19765672
TI  - Diseases and drugs that increase risk of acute large bowel ischemia.
AB  - BACKGROUND & AIMS: Information is limited on risk factors for acute large bowel
      ischemia (ALBI). We investigated diseases and drugs associated with ALBI.
      METHODS: We compared patients hospitalized with ALBI and controls through
      multivariate analysis of prior outpatient/emergency department/inpatient
      diagnoses and pharmacy dispensing records. RESULTS: There were 379 cases and 1516
      controls (median age, 69 y; range, 25-97 y; 74.4% female). Disorders that were
      diagnosed in more cases than controls, based on univariate analysis (P < .05),
      included hypertension, diabetes, chronic obstructive pulmonary disease, atrial
      fibrillation, congestive heart failure, depression, asthma, coronary artery
      disease, dementia, rheumatoid arthritis, irritable bowel syndrome, dialysis
      dependency, diarrhea, and constipation. Drugs dispensed to more cases than
      controls were antihypertensives, opioids, statins, female hormones, potentially
      constipating drugs, histamine H(2)-antagonists, immunomodulators, digoxin,
      clopidogrel/ticlopidine, taxanes/vinca alkaloids, and antibiotics. In all cases,
      ALBI was associated independently with hypertension (adjusted odds ratio [AOR],
      3.21, 95% confidence interval [CI]; 2.28-4.53; P < .0001), chronic obstructive
      pulmonary disease (AOR, 3.13; 95% CI, 2.06-4.75; P < .0001), diarrhea (AOR, 2.36;
      95% CI, 1.13-4.89; P = .0218), atrial fibrillation (AOR, 2.21; 95% CI, 1.34-3.64;
      P = .0019), congestive heart failure (AOR, 1.94; 95% CI, 1.11-3.39; P = .0205),
      diabetes (AOR, 1.82; 95% CI, 1.31-2.53; P = .0004), antibiotics (AOR, 3.30; 95%
      CI, 2.19-4.96; P < .0001), opioids (AOR, 1.96; 95% CI, 1.43-2.67; P < .0001), and
      potentially constipating drugs (AOR, 1.75; 95% CI, 1.25-2.44; P = .0012).
      Analysis of only women revealed similar associations except for diarrhea plus
      rheumatoid arthritis (AOR, 3.27; 95% CI, 1.07-9.96; P = .0370), irritable bowel
      syndrome (AOR, 2.72; 95% CI, 1.04-7.14; P = .0424), and female hormones (AOR,
      1.88; 95% CI, 1.30-2.73; P = .0009). CONCLUSIONS: Heterogeneous diseases and
      drugs increase the risk of ALBI, consistent with multifactorial pathogenesis.

PMID- 19765673
TI  - Considering the necessity of a very low carbohydrate diet on diarrhea-predominant
      irritable bowel syndrome.

PMID- 19765674
TI  - Citalopram provides little or no benefit in nondepressed patients with irritable
      bowel syndrome.
AB  - BACKGROUND & AIMS: Data on the benefit of selective serotonin reuptake inhibitors
      (SSRIs) in irritable bowel syndrome (IBS) are conflicting. The longitudinal
      relationship between clinical symptoms and sensitivity to barostat-mediated
      rectal distension in IBS remains unclear. We assessed the benefit of citalopram
      and explored the relationships between symptoms, quality of life (QOL), and
      rectal sensitivity to barostat distension in non-depressed IBS patients. METHODS:
      Patients from primary, secondary, and tertiary care settings were randomly
      assigned to receive citalopram (20 mg/day for 4 weeks, then 40 mg/day for 4
      weeks) or placebo in a study with double-masking and concealed allocation.
      Symptoms were assessed weekly, and IBS-QOL and rectal sensation by barostat were
      assessed at the beginning and end of the study. RESULTS: Patients receiving
      citalopram did not achieve a higher rate of adequate relief of IBS symptoms than
      patients receiving placebo (12/27 [44%] vs 15/27 [56%]; P = .59), regardless of
      IBS subtype. The odds ratio for weekly response with citalopram vs placebo was
      0.80 (95% confidence interval, 0.61-1.04). Improvements in specific symptom and
      IBS-QOL scores were not superior for citalopram. Changes in IBS-QOL score and
      pressure eliciting pain showed a modest correlation (r = 0.33; 95% confidence
      interval, 0.03-0.57), but changes in symptoms and IBS-QOL scores or rectal
      sensitivity were not correlated substantially. CONCLUSIONS: Citalopram was not
      superior to placebo in treating non-depressed IBS patients. Changes in symptoms
      were not substantially correlated with changes in rectal sensation assessed by
      barostat. Any benefit of citalopram in non-depressed IBS patients is likely to be
      modest at best.

PMID- 19765675
TI  - Severe gastroparesis: medical therapy or gastric electrical stimulation.

PMID- 19765676
TI  - Giant cell tumor of the common bile duct.

PMID- 19765677
TI  - Pathology analysis reveals that dysplastic pancreatic ductal lesions are frequent
      in patients with hereditary pancreatitis.
AB  - BACKGROUND & AIMS: Hereditary pancreatitis (HP) is a risk factor for pancreatic
      adenocarcinoma. We performed a retrospective, multicenter study to characterize
      and evaluate the frequency of pancreatic intraepithelial neoplasia (PanIN) and to
      describe the characteristics of fibrosis in pancreatic surgical specimens from
      patients with HP. METHODS: Samples from partial pancreatectomies (n = 13) of
      patients with HP complications (n = 12; 7 males; mean age, 24 y; 1 patient
      underwent 2 surgeries over 16 years) were analyzed by histologic and
      immunohistologic analyses; patients with suspected or proven pancreatic
      adenocarcinoma were excluded. HP diagnosis was confirmed by analysis of PRSS1
      mutations. Dysplastic lesions were described according to the PanIN
      classification. RESULTS: Eleven patients were found to have the R122H mutation in
      PRSS1 and 1 patient was found to have the N29I mutation in PRSS1. Fifty-one PanIN
      lesions were observed in 10 specimens (77%): PanIN lesions 1a, 1b, 2, and 3 were
      observed in 8, 5, 8, and 5 specimens, respectively. The median number of PanIN
      lesions was 3.5 for each specimen. The density of the lesions was 2.6 per 10
      cm(2). The size of lesions was greater than 0.5 mm in 55% of the samples. Two
      patients with PanIN-3 developed pancreatic cancer, 18 months and 44 years after
      surgery. CONCLUSIONS: PanIN lesions are frequent, severe, and occur early in the
      course of HP. Among patients with PanINs, 50% had PanIN-3 lesions. Pancreatectomy
      could be considered as a prophylactic against pancreatic cancer in patients with
      high-grade dysplasia.

PMID- 19765678
TI  - Protective effect of florfenicol on acute lung injury induced by
      lipopolysaccharide in mice.
AB  - Florfenicol, an antibiotic used to treat infection, has previously been shown to
      modulate early cytokine responses and increase mouse survival in endotoxemia. In
      the present study, we investigated in vivo the effect of florfenicol on acute
      lung injury (ALI) induced by lipopolysaccharide (LPS). In the mouse model of LPS
      induced inflammatory lung injury, we found that pretreatment with a single
      100mg/kg dose of florfenicol significantly decreases the W/D ratio of lungs and
      protein concentration in the bronchoalveolar lavage fluid (BALF) and
      significantly reduces the number of total cells, neutrophils and macrophages in
      the BALF at 24h after LPS challenge. In addition, histopathological examination
      indicates that florfenicol significantly attenuates tissue injury of the lungs in
      LPS-induced ALI. Furthermore, florfenicol also inhibits the production of several
      inflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha) at 6
      and 12h, interleukin-6 (IL-6) at 12 and 24h, and interleukin-1ss (IL-1ss) at 12h,
      in the BALF after LPS challenge. These results suggest that florfenicol protects
      against LPS-induced ALI in mice.

PMID- 19765679
TI  - Light-mediated remote control of signaling pathways.
AB  - Cell signaling networks display an extraordinary range of temporal and spatial
      plasticity. Our programmatic approach focuses on the construction of
      intracellular probes, including sensors, inhibitors, and functionally unique
      proteins that can be temporally and spatially controlled by the investigator even
      after they have entered the cell. We have designed and evaluated protein kinase
      sensors that furnish a fluorescent readout upon phosphorylation. In addition,
      since the sensors are inert (i.e., cannot be phosphorylated) until activated by
      light, they can be carried through the various stages of any given cell-based
      behavior without being consumed. Using this strategy, we have shown that PKCbeta
      is essential for nuclear envelope breakdown and thus the transition from prophase
      to metaphase in actively dividing cells. Photoactivatable proteins furnish the
      means to initiate cellular signaling pathways with a high degree of spatial and
      temporal control. We have used this approach to demonstrate that cofilin serves
      as a component of the steering apparatus of the cell. Finally, inhibitors are
      commonly used to assess the participation of specific enzymes in signaling
      pathways that control cellular behavior. We have constructed a photo
      deactivatable inhibitor, an inhibitory species that can be switched off with
      light. In the absence of light, the target enzyme is inactive due to the presence
      of the potent inhibitory molecule. Upon photolysis, the inhibitory molecule is
      destroyed and enzymatic activity is released.

PMID- 19765680
TI  - Proton transport in carbonic anhydrase: Insights from molecular simulation.
AB  - This article reviews the insights gained from molecular simulations of human
      carbonic anhydrase II (HCA II) utilizing non-reactive and reactive force fields.
      The simulations with a reactive force field explore protein transfer and
      transport via Grotthuss shuttling, while the non-reactive simulations probe the
      larger conformational dynamics that underpin the various contributions to the
      rate-limiting proton transfer event. Specific attention is given to the
      orientational stability of the His64 group and the characteristics of the active
      site water cluster, in an effort to determine both of their impact on the maximal
      catalytic rate. The explicit proton transfer and transport events are described
      by the multistate empirical valence bond (MS-EVB) method, as are alternative
      pathways for the excess proton charge defect to enter/leave the active site. The
      simulation results are interpreted in light of experimental results on the wild
      type enzyme and various site-specific mutations of HCA II in order to better
      elucidate the key factors that contribute to its exceptional efficiency.

PMID- 19765681
TI  - Challenges for CNV interpretation in clinical molecular karyotyping: lessons
      learned from a 1001 sample experience.
AB  - Molecular karyotyping has moved from bench to bedside for the genetic screening
      of patients with mental retardation and/or congenital anomalies. The commercial
      availability of high-resolution microarray platforms has significantly
      facilitated this process. However, the notion that copy number variants are also
      abundantly present in the general population challenges the interpretation of the
      clinical significance of detected copy number variants (CNVs) in these patients.
      Moreover, the awareness of incomplete penetrance and variable expression,
      exemplified by the inheritance of causal CNVs from apparently unaffected parents,
      has further blurred the boundary between benign and pathogenic variation. We
      analyzed 1001 patients using a large insert clone array (298 patients) and an
      oligonucleotide-based (703 patients) platform. In this cohort we encountered
      several examples of causal imbalances that could have been easily interpreted as
      benign variants when relying on established paradigms. Based on our experience
      and the pitfalls we encountered, we suggest a decision tree that can be used as a
      guideline in clinical diagnostics. Using this workflow, we detected 106
      clinically significant CNVs in 100 patients, giving a diagnostic yield of at
      least 10%. Of these imbalances, 58 occurred de novo, 22 were inherited and 26 of
      unknown inheritance. This underscores that inherited CNVs should not be
      automatically disregarded as benign variants. Among the clinically relevant CNVs
      were 11 single-gene aberrations, highlighting the power of high-resolution
      molecular karyotyping to identify causal genes.

PMID- 19765682
TI  - A homozygous nonsense mutation in the human desmocollin-3 (DSC3) gene underlies
      hereditary hypotrichosis and recurrent skin vesicles.
AB  - Desmosomes are the major players in epidermis and cardiac muscles and contribute
      to intercellular binding and maintenance of tissue integrity. Two important
      constituents of desmosomes are transmembrane cadherins named desmogleins and
      desmocollins. The critical role of these desmosomal proteins in epithelial
      integrity has been illustrated by their disruption in mouse models and human
      diseases. In the present study, we have investigated a large family from
      Afghanistan in which four individuals are affected with hereditary hypotrichosis
      and the appearance of recurrent skin vesicle formation. All four affected
      individuals showed sparse and fragile hair on scalp, as well as absent eyebrows
      and eyelashes. Vesicles filled with thin, watery fluid were observed on the
      affected individuals' scalps and on most of the skin covering their bodies. A
      scalp-skin biopsy of an affected individual showed mild hair-follicle plugging.
      Candidate-gene-based homozygosity linkage mapping assigned the disease locus to
      8.30 cM (8.51 Mbp) on chromosome 18q12.1. A maximum multipoint LOD score of 3.30
      (theta = 0.00) was obtained at marker D18S877. Sequence analysis of four
      desmoglein and three desmocollin genes, contained within the linkage interval,
      revealed a homozygous nonsense mutation (c.2129T>G [p.Leu710X]) in exon-14 of the
      desmocollin-3 (DSC3) gene.

PMID- 19765684
TI  - Effects of suppression and appraisals on thought frequency and distress.
AB  - Cognitive theories of obsessions highlight appraisals of personal significance
      and thought suppression in the development and maintenance of intrusive thoughts.
      The current study examined the role of personal significance within the context
      of a thought suppression paradigm. The primary aim was to examine whether
      suppression would have differential effects for target thoughts appraised as
      personally meaningful versus relatively unimportant. A blasphemous thought served
      as the target thought, and highly religious and nonreligious participants were
      recruited. Participants completed a two-interval thought suppression task; during
      interval 1 they were randomly assigned to suppress or not suppress the target
      thought and during interval 2, all participants were given "do not suppress"
      instructions. Suppression resulted in sustained frequency of thoughts in contrast
      to the decline in thought frequency observed for non-suppression. Differential
      effects of suppression were found across the two groups. Moreover, suppression
      was associated with increased negative mood and anxiety. Results suggest that
      suppression of personally meaningful thoughts is a counterproductive strategy.

PMID- 19765683
TI  - Heterozygous NTF4 mutations impairing neurotrophin-4 signaling in patients with
      primary open-angle glaucoma.
AB  - Glaucoma, a main cause of blindness in the developed world, is characterized by
      progressive degeneration of retinal ganglion cells (RGCs), resulting in
      irreversible loss of vision. Although members of the neurotrophin gene family in
      various species are known to support the survival of numerous neuronal
      populations, including RGCs, it is less clear whether they are also required for
      survival and maintenance of adult neurons in humans. Here, we report seven
      different heterozygous mutations in the Neurotrophin-4 (NTF4) gene accounting for
      about 1.7% of primary open-angle glaucoma patients of European origin. Molecular
      modeling predicted a decreased affinity of neurotrophin 4 protein (NT-4) mutants
      with its specific tyrosine kinase receptor B (TrkB). Expression of recombinant NT
      4 carrying the most frequent mutation was demonstrated to lead to decreased
      activation of TrkB. These findings suggest a pathway in the pathophysiology of
      glaucoma through loss of neurotrophic function and may eventually open the
      possibility of using ligands activating TrkB to prevent the progression of the
      disease.

PMID- 19765685
TI  - Is manipulation of mood a critical component of cognitive bias modification
      procedures?
AB  - This paper investigates whether changes in mood state are an important component
      of cognitive bias modification (CBM) procedures. In a novel CBM procedure
      participants read either positive or negative statements relating to social
      issues for 5 min. Interpretation bias was measured by means of a scrambled
      sentence test, which was presented both before and after the CBM procedure.
      Participants who read the positive statements made more positive resolutions to
      the scrambled sentences, while participants who read the negative statements made
      more negative resolutions. Thus, the appropriate positive and negative
      interpretative biases were induced by the CBM procedure. However, significant
      mood changes also occurred following CBM. In Experiment 2, a musical mood
      induction procedure was presented with depressing or elating music. As before, a
      scrambled sentence test was presented both before and after the musical mood
      induction. Mood changed in accordance with the valence of the music to the same
      extent as with CBM. Critically however, performance on the scrambled sentence
      task did not change for both groups. This demonstrates that a change in mood
      state is not sufficient for a change in cognitive bias to occur.

PMID- 19765686
TI  - Error-related processing dysfunction in children aged 9 to 12 years presenting
      putative antecedents of schizophrenia.
AB  - BACKGROUND: Intervention aimed at preventing schizophrenia may be most effective
      if targeted at specific, but modifiable, functional impairments that present
      during childhood. We have developed a novel method of screening community samples
      aged 9 to 12 years to identify children who present a triad of putative
      antecedents of schizophrenia (ASz), defined as 1) speech and/or motor development
      lags/problems; 2) internalizing, externalizing, and/or peer-relationship problems
      in the clinical range; and 3) psychotic-like experiences. This study examined
      whether ASz children display brain function abnormalities during error processing
      that are similar to those exhibited by adults with schizophrenia. METHODS: Twenty
      two ASz children and 26 typically developing (TD) children with no antecedents of
      schizophrenia completed an error-inducing Go/NoGo task during event-related
      potential recording. Group differences were examined in the amplitude and latency
      of four event-related potential components: the initial error-related negativity
      (ERN) and later error-positivity (Pe) elicited on false-alarm responses to NoGo
      trials, and the corresponding initial correct response negativity (CRN) and later
      correct response positivity (Pc) elicited during processing of correct responses
      to Go trials. RESULTS: Relative to TD children, ASz children were characterized
      by reduced ERN amplitude but unaffected CRN, Pe, and Pc amplitudes. No group
      differences were observed in the latency of any component. CONCLUSIONS: Children
      presenting a triad of putative antecedents of schizophrenia show error-processing
      dysfunction mimicking that observed in adults with schizophrenia using the same
      Go/NoGo paradigm. The ASz children displayed specific early error-processing
      deficits rather than a generalized deficit in self-monitoring.

PMID- 19765687
TI  - Modulation of chromatin modification facilitates extinction of cocaine-induced
      conditioned place preference.
AB  - BACKGROUND: Recent evidence suggests that epigenetic mechanisms have an important
      role in the development of addictive behavior. However, little is known about the
      role of epigenetic mechanisms in the extinction of drug-induced behavioral
      changes. In this study, we examined the ability of histone deacetylase (HDAC)
      inhibitors to facilitate extinction and attenuate reinstatement of cocaine
      induced conditioned place preference (CPP). METHODS: C57BL/6 mice were subject to
      cocaine-induced CPP using 20 mg/kg dose. To facilitate extinction, mice were
      administered an HDAC inhibitor following nonreinforced exposure to the
      conditioned context. To measure persistence, mice were subject to a reinstatement
      test using 10 mg/kg dose of cocaine. RESULTS: We demonstrate that HDAC inhibition
      during extinction consolidation can facilitate extinction of cocaine-induced CPP.
      Animals treated with an HDAC inhibitor extinguished cocaine-induced CPP both more
      quickly and to a greater extent than did vehicle-treated animals. We also show
      that the extinction of cocaine seeking via HDAC inhibition modulates extinction
      learning such that reinstatement behavior is significantly attenuated.
      Acetylation of histone H3 in the nucleus accumbens following extinction was
      increased by HDAC inhibition. CONCLUSIONS: This study provides the first evidence
      that modulation of chromatin modification can facilitate extinction and prevent
      reinstatement of drug-induced behavioral changes. These findings provide a
      potential novel approach to the development of treatments that facilitate
      extinction of drug-seeking behavior.

PMID- 19765689
TI  - Reduced early auditory evoked gamma-band response in patients with schizophrenia.
AB  - BACKGROUND: There is growing evidence for abnormalities of certain gamma
      aminobutyric acid (GABA)-ergic interneurons and their interaction with
      glutamatergic pyramidal cells in schizophrenia. These interneurons are critically
      involved in generating neural activity in the gamma-band (30-100 Hz) of the
      electroencephalogram. One example of such gamma oscillations is the early
      auditory evoked gamma-band response (GBR). Although auditory processing is
      obviously disturbed in schizophrenia, there is no direct evidence providing a
      reduced early auditory evoked GBR so far. We addressed two questions: 1) Is the
      early auditory evoked GBR decreased regarding power and phase-locking in
      schizophrenic patients?; and 2) Is this possible decrease a result of reduced
      activity in the auditory cortex and/or the anterior cingulate cortex (ACC), which
      were identified as sources of the GBR previously? METHODS: We investigated the
      early auditory evoked GBR and its sources in the ACC and the auditory cortex in
      90 medicated patients with schizophrenia and in age-, gender-, and education
      matched healthy control subjects with an auditory reaction task. RESULTS:
      Patients with schizophrenia showed a significant reduction of power and phase
      locking of the early auditory evoked GBR. This effect was due to a reduced
      activity in the auditory cortex and the ACC/medial frontal gyrus region (low
      resolution brain electromagnetic tomography analysis). CONCLUSIONS: Generally,
      these findings are in line with earlier reports on the impaired ability of
      schizophrenic patients in generating gamma activity. In addition, this is the
      first study to demonstrate disturbance of gamma activity in auditory processing
      as assessed by the early auditory GBR power.

PMID- 19765688
TI  - Atypical face versus object processing and hemispheric asymmetries in 10-month
      old infants at risk for autism.
AB  - BACKGROUND: Previous studies have documented atypicalities in face/object
      processing in children and adults with autism spectrum disorders (ASDs). To
      investigate whether such atypicalities may reflect a genetically mediated risk
      factor present early in development, we measured face/object processing in 10
      month-old high-risk infants who carry some of the genes associated with ASD
      because they have an older sibling diagnosed with the disorder. METHODS: We
      employed event-related potentials (ERPs) to measure cortical responses to
      pictures of faces and objects, the objects being toys. Latencies and amplitudes
      of four ERP components (P100, N290, P400, and Nc) were compared between 20 high
      risk infants and 20 low-risk control subjects (infants with no family history of
      ASD). RESULTS: Responses to faces versus objects differed between high- and low
      risk infants for the latencies of the N290 and P400. Differences were driven by
      faster responses to faces than objects in low-risk, but not high-risk, infants
      (P400) and, conversely, faster responses to objects than faces in high-risk, but
      not low-risk, infants (N290). Object responses were also faster in high-risk than
      low-risk infants (both N290 and P400). Left versus right hemisphere responses
      also differed between high- and low-risk infants for the amplitudes of the P100,
      N290, and P400; collapsed across faces/objects, low-risk, but not high-risk,
      infants exhibited hemisphere asymmetries. CONCLUSIONS: Genetic risk for ASD is
      associated with atypical face versus object processing and an atypical lack of
      hemispheric asymmetry early in life. These atypicalities might contribute to
      development of the disorder.

PMID- 19765690
TI  - Chemical analysis of a polysaccharide of unripe (green) tomato (Lycopersicon
      esculentum).
AB  - A polysaccharide (PS-I) isolated from the aqueous extract of the unripe (green)
      tomatoes (Lycopersicon esculentum) consists of D-galactose, D-methyl
      galacturonate, D-arabinose, L-arabinose, and L-rhamnose. Structural investigation
      of the polysaccharide was carried out using total acid hydrolysis, methylation
      analysis, periodate oxidation study, and NMR studies ((1)H, (13)C, DQF-COSY,
      TOCSY, NOESY, ROESY, HMQC, and HMBC). On the basis of above-mentioned experiments
      the structure of the repeating unit of the polysaccharide (PS-I) was established
      as: [structure: see text].

PMID- 19765691
TI  - Iodine-promoted ribosylation leads to a facile acetonide-forming reaction.
AB  - Iodine not only promotes smooth beta-selective glycosylation of ribose tetra
      acetate under exceptionally mild conditions, it also catalyzes an expedient
      acetonide-forming reaction in this system when dry acetone is used as a solvent.

PMID- 19765692
TI  - Influence of oxidative and osmotic stresses on the structure of the cell wall
      mannan of Candida albicans serotype A.
AB  - In this study, we investigated the structural changes in the cell wall mannan of
      Candida albicans serotype A strain cells cultured under various stress
      conditions, that is, oxidative stress of 3.5 mM H(2)O(2), osmotic stress of 1.5M
      NaCl, and heat stress at 37 degrees C, compared with the normal condition of 30
      degrees C in yeast extract-added Sabouraud liquid medium (YSLM). Based on the
      (1)H nuclear magnetic resonance (NMR) and fluorophore-assisted carbohydrate
      electrophoresis (FACE) analyses of the mannans, we showed that the proportion of
      the terminal beta-1,2-linked mannose side chain unit in the mannan increased in
      the cell proliferation process under both the normal condition and the oxidative
      stress condition. The osmotic stress induced a slight decrease in the proportion
      of the beta-1,2-linked mannose unit in the acid-labile fraction. The heat stress
      induced a significant decrease in the proportions of the beta-1,2-linked mannose
      unit in both the acid-labile and acid-stable fractions. Based on these results,
      we propose that C. albicans significantly changes the mannan structures under
      various stress conditions and that sufficient attention to the cultural
      conditions is needed to perform an accurate diagnosis of candidiasis.

PMID- 19765693
TI  - A sugar-aza-crown ether-based fluorescent sensor for Hg(2+) and Cu(2+).
AB  - A fluorescent sensor, 5, based upon the sugar-aza-crown ether structure with two
      anthracenetriazolymethyl groups was prepared and its fluoroionophoric properties
      toward transition metal ions were investigated. In methanol, the sensor exhibits
      highly selective recognition of Cu(2+) and Hg(2+) ions among a series of tested
      metal ions. The association constant for 5.Cu(2+) and 5.Hg(2+) in methanol was
      calculated to be 4.0 x 10(5)M(-1) and 1.1 x 10(5)M(-1), respectively. The
      detection limits for the sensing of Cu(2+) and Hg(2+) ions were 1.39 x 10(-6)M
      and 1.39 x 10(-5) M, respectively.

PMID- 19765694
TI  - Synthesis and characterization of mannosylated oligoribonucleotides.
AB  - Oligoribonucleotide (RNA)-carbohydrate conjugates bearing mono- and divalent
      mannosides were readily obtained using 3,4-diethoxy-3-cyclobutene-1,2-dione as
      the linking agent in the presence of trace amount of triethylamine. The
      glycoconjugates were purified by HPLC and characterized by electrospray mass
      spectroscopy.

PMID- 19765695
TI  - [Phlebology training during MIR].

PMID- 19765696
TI  - [Acute typhlitis as a cause of pneumoperitoneum in a non-neutropenic patient].

PMID- 19765697
TI  - [Cutaneous ulceration of the breast: an unusual presentation of Wegener's
      granulomatosis].

PMID- 19765698
TI  - Learning words' sounds before learning how words sound: 9-month-olds use distinct
      objects as cues to categorize speech information.
AB  - One of the central themes in the study of language acquisition is the gap between
      the linguistic knowledge that learners demonstrate, and the apparent inadequacy
      of linguistic input to support induction of this knowledge. One of the first
      linguistic abilities in the course of development to exemplify this problem is in
      speech perception: specifically, learning the sound system of one's native
      language. Native-language sound systems are defined by meaningful contrasts among
      words in a language, yet infants learn these sound patterns before any
      significant numbers of words are acquired. Previous approaches to this learning
      problem have suggested that infants can learn phonetic categories from
      statistical analysis of auditory input, without regard to word referents.
      Experimental evidence presented here suggests instead that young infants can use
      visual cues present in word-labeling situations to categorize phonetic
      information. In Experiment 1, 9-month-old English-learning infants failed to
      discriminate two non-native phonetic categories, establishing baseline
      performance in a perceptual discrimination task. In Experiment 2, these infants
      succeeded at discrimination after watching contrasting visual cues (i.e., videos
      of two novel objects) paired consistently with the two non-native phonetic
      categories. In Experiment 3, these infants failed at discrimination after
      watching the same visual cues, but paired inconsistently with the two phonetic
      categories. At an age before which memory of word labels is demonstrated in the
      laboratory, 9-month-old infants use contrastive pairings between objects and
      sounds to influence their phonetic sensitivity. Phonetic learning may have a more
      functional basis than previous statistical learning mechanisms assume: infants
      may use cross-modal associations inherent in social contexts to learn native
      language phonetic categories.

PMID- 19765699
TI  - The distribution of subjective memory strength: list strength and response bias.
AB  - Models of recognition memory assume that memory decisions are based partially on
      the subjective strength of the test item. Models agree that the subjective
      strength of targets increases with additional time for encoding however the
      origin of the subjective strength of foils remains disputed. Under the fixed
      strength assumption the distribution of memory strength for foils is invariant
      across experimental manipulations of encoding. For example, the subjective
      strength of foils may depend solely on the pre-experimental history of the item,
      thus encoding manipulations have no impact. In contrast, under the
      differentiation assumption the subjective strength of foils depends on the nature
      of the traces stored in episodic memory. If those traces are well encoded, the
      subjective strength of foils will be lower than the case where noisy traces are
      stored (e.g., when targets received minimal encoding). The fixed strength and
      differentiation accounts are tested by measuring direct ratings of memory
      strength. In Experiments 1 and 2, item strength is varied via repetition and in
      Experiment 3 response bias is varied via the relative proportion of targets on
      the test list. For all experiments empirical distributions of memory strength
      were obtained and compared to the distributions predicted by the two accounts.
      The differentiation assumption provides the most parsimonious account of the
      data.

PMID- 19765700
TI  - Metabolism of triglyceride-rich lipoproteins and lipid transfer to high-density
      lipoprotein in young obese and normal-weight patients with polycystic ovary
      syndrome.
AB  - OBJECTIVE: To clarify whether the metabolism of triglyceride-rich lipoproteins
      and lipid transfer to high-density lipoprotein (HDL) are altered in patients with
      polycystic ovary syndrome (PCOS). DESIGN: Case-control study. SETTING:
      Endocrinology clinics. PATIENT(S): Eight normal-weight (NW) and 15 obese (Ob)
      patients with PCOS were compared with 10 NW and 10 Ob women without PCOS paired
      for age and body mass index. INTERVENTION(S): Determination of triglyceride-rich
      lipoprotein metabolism and lipid transfer to HDL. MAIN OUTCOME MEASURE(S):
      Participants were injected triglyceride-rich emulsions labeled with (14)C
      cholesteryl esters and (3)H-triglycerides and the fractional clearance rate (FCR,
      in min(-1)) of labels was determined. Lipid transfer from artificial
      nanoemulsions to HDL was performed by incubating radioactively labeled lipid
      nanoemulsions with plasma during 1 hour, followed by radioactive counting of HDL
      containing supernatant after chemical precipitation. RESULT(S): Lipolysis
      estimated by triglyceride FCR was equal in PCOS groups (NW = 0.043 +/- 0.032, Ob
      = 0.033 +/- 0.009) and respective controls (NW = 0.039 +/- 0.015, Ob = 0.044 +/-
      0.019). However, the remnant removal as estimated by cholesteryl ester FCR was
      reduced in both PCOS groups (NW = 0.005 +/- 0.006, Ob = 0.005 +/- 0.005) compared
      with controls (NW = 0.016 +/- 0.006, Ob = 0.011 +/- 0.072). Lipid transfer rates
      were not different among groups, but triglyceride transfer rates were positively
      correlated with homeostasis model assessment estimate of insulin resistance in
      PCOS. CONCLUSION(S): PCOS patients showed decreased removal of atherogenic
      remnants even when fasting glucose was <100 mg/dL. This reinforces the usefulness
      of the measures taken to prevent cardiovascular events in PCOS patients.

PMID- 19765701
TI  - Polymorphisms in the protein C inhibitor gene in in vitro fertilization failure.
AB  - The aim of this study was to determine whether total fertilization failure in
      human IVF can be partially explained by alterations in the gene that codes for
      protein C inhibitor. Forty-six men had IVF total fertilization failure and 51
      controls with normal fertilization were screened for mutations in the protein C
      inhibitor gene by direct sequencing. The main finding was that in men involved in
      total fertilization failure, a heterozygous adenosine/guanine (A/G) base
      combination in position 1389 (rs2069990) (exon 6) in the protein C inhibitor gene
      was significantly more common compared with controls (10.9% vs. 0).

PMID- 19765703
TI  - Successful treatment of cesarean scar pregnancy using laparoscopically assisted
      local injection of etoposide with transvaginal ultrasound guidance.
AB  - OBJECTIVE: To present a case of cesarean scar ectopic pregnancy (CSEP)
      successfully diagnosed and treated with a laparoscopic local injection of 100 mg
      etoposide under transvaginal ultrasound assistance. DESIGN: Case report. SETTING:
      University-affiliated teaching hospital. PATIENT(S): A 37-year-old woman with
      CSEP. INTERVENTION(S): Local injection of 100 mg etoposide. MAIN OUTCOME
      MEASURE(S): Serial serum levels of beta-hCG and return of normal menstruation.
      RESULT(S): Serial serum beta-hCG levels were 572.2 mIU/mL before operation, 340.7
      mIU/mL on the first postoperative day, 28.1 mIU/mL on postoperative day 9, and 5
      mIU/mL on postoperative day 17. Menstruation was initiated on postoperative day
      45. CONCLUSION(S): Use of laparoscopic local injection of 100 mg etoposide with
      transvaginal ultrasound guidance might be an effective method for the management
      of CSEP.

PMID- 19765702
TI  - Effects of taxane-based chemotherapy on inhibin B and gonadotropins as biomarkers
      of spermatogenesis.
AB  - OBJECTIVE: To assess the effects of taxane-based chemotherapy on the male
      reproductive axis, and, therefore, its impact on spermatogenesis and fertility.
      DESIGN: Controlled clinical study. SETTING: Patients with cancer in an academic
      research environment. PATIENT(S): Forty male patients of reproductive age with
      cancer with solid tumor at diagnosis, who had been scheduled to receive taxane
      based chemotherapy. INTERVENTION(S): The patients were given treatment with
      docetaxel or paclitaxel combined with gemcitabine or carboplatin. Blood sampling
      and testicular ultrasonography were performed before and after completion of
      chemotherapy. MAIN OUTCOME MEASURE(S): In all patients, serum levels of inhibin
      B, FSH, and LH were measured, and, in half of the patients, bilateral testicular
      volume was also measured. RESULT(S): There was a statistically significant
      decrease in serum inhibin B and increase in serum FSH in all patients after the
      completion of the taxane-based chemotherapy. The median LH levels did not exhibit
      a statistically significant increase after the last cycle. Bilateral testicular
      volume exhibited a statistically significant decrease in 19 out of 20 patients
      (95%) after completion of chemotherapy. CONCLUSION(S): Taxane-based chemotherapy
      induces the reduction of inhibin B and the reciprocal elevation of FSH, which are
      associated with significant gonadal damage in the early stages after completion
      of chemotherapy.

PMID- 19765704
TI  - Aberrant implantation and growth of uterine leiomyoma in the abdominal wall after
      laparoscopically assisted myomectomy.
AB  - OBJECTIVE: To report a case of aberrant implantation and growth of uterine
      leiomyoma in the abdominal wall after laparoscopically assisted myomectomy.
      DESIGN: Case report. SETTING: University hospital. PATIENT(S): One 27-year-old
      woman with a newly developed solid mass in the abdominal wall near the
      minilaparotomic site of a previous laparoscopically assisted myomectomy.
      INTERVENTION(S): Surgical removal of the mass. MAIN OUTCOME MEASURE(S):
      Histologic examination of the mass. RESULT(S): A newly developed mass measuring
      approximately 9 cm was surgically removed. The mass was located in the fascial
      area of abdomen close to the incision site of a previous laparoscopically
      assisted myomectomy. Histologic diagnosis including Hematoxylin-Eosin staining
      and immunohistochemistry confirmed that the lesion was compatible with uterine
      leiomyoma. CONCLUSION(S): Implantation and growth of uterine leiomyoma fragments
      after myomectomy is a rare event. However, this complication should be considered
      as a differential diagnosis when a progressively growing mass is observed at the
      incision site.

PMID- 19765705
TI  - The therapeutic management of a twin pregnancy complicated by the presence of
      cervical cancer, following laparoscopic staging and chemotherapy, with an
      emphasis on cisplatin concentrations in the fetomaternal compartments amnion
      fluid, umbilical cord, and maternal serum.
AB  - OBJECTIVE: To evaluate the feasibility, toxicity, and pharmacokinetics in the
      maternal and fetal compartments during chemotherapy in a pregnant patient with
      cervical cancer. DESIGN: Case report. SETTING: University Hospital. PATIENT: A 35
      year-old woman was diagnosed with an adenocarcinoma FIGO stage IB1 of the cervix
      uteri at 14 weeks' gestation with twin pregnancy. INTERVENTION(S): A laparoscopic
      transperitoneal pelvic lymphadenectomy was performed at 15 weeks' gestation There
      was no evidence of lymph node metastases (0/19). The patient decided to continue
      her pregnancy. Three cycles of neoadjuvant chemotherapy consisting of cisplatin
      during the second and third trimester were given and well tolerated.
      Amniocentesis was performed at the time of the second cisplatin cycle. MAIN
      OUTCOME MEASURE(S) AND RESULT(S): The concentration in the amniotic fluid samples
      reached 10% of the maternal blood levels at this time. At 32 weeks' gestation, a
      Caesarean section followed by radical hysterectomy was performed. The twins
      developed normally and displayed no chemotherapically related side effects. At
      the time of delivery, the corresponding concentration in the amniotic fluid was
      approximately one-third of the umbilical cord levels. CONCLUSION(S): To our
      knowledge, this is the first report quantifying the amount of transplacental
      transport of cisplatin during pregnancy in vivo. One-tenth of the maternal serum
      concentration was detected in the amniotic fluid; the concentration of cisplatin
      in the umbilical cord was three times higher than in the amniotic fluid.

PMID- 19765706
TI  - [Analysis of operative indications and outcomes in 238 re-operations after
      abdominal surgery in an economically disadvantaged setting].
AB  - AIM OF THE STUDY: We analyse aspects of re-operative abdominal surgery in an
      economically disadvantaged environment with respect to indications, operative
      findings, treatment modalities, and outcomes. PATIENTS AND METHODS: Retrospective
      chart review over a seven-year period of patients requiring re-operative surgery
      during the same hospitalization or within 30 days of initial surgery. RESULTS:
      During the study period, 7714 laparotomies were performed. Two hundred and
      seventy-seven (3.6%) required re-operation; of these, 238 charts (86%) were able
      to be reviewed. The decision for operative re-intervention was made mainly on the
      basis of clinical findings. Postoperative peritonitis (50.8%), adhesive bowel
      obstruction (23.9%), and intestinal fistula (10.9%) were the main indications for
      re-intervention. Complications occurred in 35% and included postoperative
      infection (n=70, 33%) and abdominal wall dehiscence (n=37, 15.5%). Mortality was
      18% and increased significantly when the initial operative procedure was for
      peritonitis and re-operation was due to septic complications. CONCLUSION: In an
      economically disadvantaged environment, the re-operation rate after an abdominal
      surgery does not seem to be higher than that seen in series from developed
      countries, although there may be factors which bias this observation. The
      mortality rate for cases with postoperative peritonitis is high, but operative re
      intervention based on clinical findings is still considered the favored strategy
      in our environment. Results may improve with better material medical conditions.

PMID- 19765707
TI  - Tangier disease caused by compound heterozygosity for ABCA1 mutations R282X and
      Y1532C.
AB  - BACKGROUND: Inherited low levels of high density lipoprotein (HDL) cholesterol
      may be due to mutations in the genes encoding the ATP-binding cassette
      transporter A1 (ABCA1), apolipoprotein (apo) A-I or lecithin:cholesterol
      acyltransferase (LCAT). METHODS: The ABCA1, apoA-I and LCAT genes of a 40-year
      old male subject with serum HDL cholesterol of 0.06mmol/l were subjected to DNA
      sequencing. The proband's family was examined for co-segregation between
      mutations and levels of HDL cholesterol. Cholesterol efflux in fibroblasts from
      the proband and a normocholesterolemic subject was compared. The effects of an
      ABCA1 mutation on cholesterol efflux and membrane localization of ABCA1 were
      studied in transfected HEK293 and HeLa cells, respectively. RESULTS: The proband
      was a compound heterozygote for ABCA1 mutations R282X (c.844 C>T) and Y1532C
      (c.4595 A>G). Relatives who were heterozygous for one of these mutations, had
      about half-normal HDL cholesterol levels. Cholesterol efflux was reduced in
      fibroblasts from the proband, as was cholesterol efflux from HEK293 cells
      transfected with an human (h) ABCA1 expression plasmid harboring the Y1532C
      mutation. Confocal microscopy of HeLa cells transfected with the Y1532C-hABCA1
      plasmid revealed that the Y1532C mutation inhibits ABCA1 from reaching the
      cellular membrane. CONCLUSION: Compound heterozygosity for the nonsense mutation
      R282X and the missense mutation Y1532C in the ABCA1 gene causes Tangier disease.
      R282X has a detrimental effect on the function of ABCA1 since a premature stop
      codon is introduced. Mutation Y1532C disrupts the normal function of ABCA1 as
      determined by in vitro analyses.

PMID- 19765708
TI  - The associations between visceral fat and calcified atherosclerosis are stronger
      in women than men.
AB  - BACKGROUND: Previous studies have found a significant association between body
      mass index (BMI) and coronary artery calcium (CAC). Little is known about whether
      body fatness is linked with atherosclerotic calcium (AC) in the non-coronary
      vasculature. Accordingly, this study tested the hypothesis that there would be
      significant associations between CAC and AC in the non-coronary vasculature and
      BMI, visceral fat (VF), and percent body fat (BF%). METHODS: Subjects (n=1160;
      mean age 57 years; 55% men) underwent electron beam computed tomography (EBCT)
      screening for AC in the carotid, coronary, thoracic and abdominal aorta, and
      iliac arteries. Visceral fat and BF% were measured using EBCT and electrical
      bioimpedance analysis, respectively. RESULTS: In sex-stratified models adjusted
      for CVD risk factors, there were significant associations among both sexes
      between 1-SD increments of BMI, BF% and VF and the presence of CAC (p<0.01) as
      well as for quartiles of BMI and VF and prevalent CAC. Higher levels (tertiles)
      of BF% and VF were significantly associated with higher amounts of both abdominal
      aortic calcium (OR=1.90, 1.57 with p=0.02, 0.05 in females and males,
      respectively) and CAC. CONCLUSIONS: Measures of body morphology are significantly
      associated with AC in the coronary arteries and abdominal aorta. Of the measures
      studied, VF appears to be the most relevant by having the most consistent and
      stronger magnitudes of association, especially in women. These results suggest
      that VF may be more relevant in women than men with respect to the presence and
      extent of atherosclerosis in multiple vascular beds.

PMID- 19765709
TI  - Vaccination against Foxp3(+) regulatory T cells aggravates atherosclerosis.
AB  - OBJECTIVE: Regulatory T cells are crucial for immune homeostasis and an impaired
      regulatory T cell function results in many pathological conditions. Regulatory T
      cells have already been described to be protective in atherosclerosis. However
      the exact contribution of Foxp3-expressing natural regulatory T cells in
      atherosclerosis has not been elucidated yet. METHODS AND RESULTS: In this study
      we vaccinated LDL receptor deficient mice with dendritic cells which are
      transfected with Foxp3 encoding mRNA and studied the effect on initial
      atherosclerosis. Vaccination against Foxp3 resulted in a reduction of Foxp3(+)
      regulatory T cells in several organs and in an increase in initial
      atherosclerotic lesion formation. Furthermore we observed an increase in plaque
      cellularity and increased T cell proliferation in the Foxp3 vaccinated mice.
      CONCLUSION: We further establish the protective role of Tregs in atherosclerosis.
      The results illustrate the important role for Foxp3-expressing regulatory T cells
      in atherosclerosis, thereby providing a potential opportunity for therapeutic
      intervention against this disease.

PMID- 19765710
TI  - Sarcomere dynamics in skeletal muscle myofibrils during isometric contractions.
AB  - The main goal of this study was to evaluate the dynamics of sarcomeres during
      isometric activation of skeletal muscle myofibrils. Rabbit psoas myofibrils
      (n=14) were attached between a pair of cantilevers for force measurements at one
      side and a rigid glass needle at the other side, and their images were used for
      measurements of individual sarcomere lengths (SL) during contractions. Myofibrils
      were set at average SL between 2.13 and 3.06 microm, and were activated and held
      isometric for 20-35s during which SL and force were continuously measured. SL
      dispersion increased from the rest state to activation, but it remained mostly
      constant during the activation period. Even with the length non-uniformity
      developed during myofibril activation, most sarcomeres stabilized their length
      changes during the isometric contraction. As a result, sarcomeres contracted at
      different degrees of filament overlap while producing similar forces. When the
      myofibrils were separated in two groups that produced force at averaged short (<
      or =2.5 microm) or long (> or =2.5 microm) SL, the initial non-uniformity was
      greater in long lengths, but changes observed in sarcomeres during the activation
      period were similar, suggesting that sarcomere stability is not length-dependent.

PMID- 19765711
TI  - Fluid-structure interaction analysis of turbulent pulsatile flow within a layered
      aortic wall as related to aortic dissection.
AB  - Turbulent pulsatile flow and wall mechanics were studied numerically in an
      axisymmetric three-layered wall model of a descending aorta. The transport
      equations were solved using the finite element formulation based on the Galerkin
      method of weighted residuals. A fully-coupled fluid-structure interaction (FSI)
      analysis was utilized in this investigation. We calculated Von Mises wall stress,
      streamlines and fluid pressure contours. The findings of this study show that
      peak wall stress and maximum shear stress are highest in the media layer. The
      difference in the elastic properties of contiguous layers of the wall of the
      aorta probably determines the occurrence of dissection in the media layer.
      Moreover, the presence of aortic intramural hematoma is found to have a
      significant effect on the peak wall stress acting on the inner layer.

PMID- 19765712
TI  - Post-yield relaxation behavior of bovine cancellous bone.
AB  - Relaxation studies were conducted on specimens of bovine cancellous bone at post
      yield strains. Stress and strain were measured for 1000s and the relaxation
      modulus was determined. Fifteen cylindrical, cancellous bone specimens were
      removed from one bovine femur in the anterior-posterior direction. The relaxation
      modulus was found to be a function of strain. Therefore cancellous bone is non
      linearly viscoelastic/viscoplastic in the plastic region. A power law regression
      was fit to the relaxation modulus data. The multiplicative constant was found to
      be statistically related through a power law relationship to both strain
      (p<0.0005) and apparent density (p<0.0005) while the power coefficient was found
      to be related through a power law relationship, E(t, epsilon)=A(epsilon)t(
      n(epsilon)), to strain (p<0.0005), but not apparent density.

PMID- 19765713
TI  - Comparison of analytical and inverse finite element approaches to estimate cell
      viscoelastic properties by micropipette aspiration.
AB  - The viscoelastic properties of cells are important in predicting cell deformation
      under mechanical loading and may reflect cell phenotype or pathological
      transition. Previous studies have demonstrated that viscoelastic parameters
      estimated by finite element (FE) analyses of micropipette aspiration (MA) data
      differ from those estimated by the analytical half-space model. However, it is
      unclear whether these differences are statistically significant, as previous
      studies have been based on average cell properties or parametric analyses that do
      not reflect the inherent experimental and biological variability of real
      experimental data. To determine whether cell material parameters estimated by the
      half-space model are significantly different from those predicted by the FE
      method, we implemented an inverse FE method to estimate the viscoelastic
      parameters of a population of primary porcine aortic valve interstitial cells
      tested by MA. We found that inherent differences between the analytical and
      inverse FE estimation methods resulted in statistically significant differences
      in individual cell properties. However, in cases with small pipette to cell
      radius ratios and short loading periods, model-dependent differences were masked
      by experimental and cell-to-cell variability. Analytical models that account for
      finite cell-size and loading rate further relaxed the experimental conditions for
      which accurate cell material parameter estimates could be obtained. These data
      provide practical guidelines for analysis of MA data that account for the wide
      range of conditions encountered in typical experiments.

PMID- 19765714
TI  - Use of capillary electrophoresis with laser-induced fluorescence detection to
      screen and liquid chromatography-tandem mass spectrometry to confirm sulfonamide
      residues: validation according to European Union 2002/657/EC.
AB  - A multiresidue method is described for determining six sulfonamides (SAs)
      (sulfadiazine, sulfathiazole, sulfamethazine, sulfamethoxazole, sulfaquinoxaline
      and sulfadimethoxine) in liver by a capillary electrophoresis screening method
      and a liquid chromatography coupled to tandem mass spectrometry confirmatory
      assay. Samples were prepared by homogenizing the tissue, with sodium hydroxide
      and acetonitrile. After evaporation, extracts were injected in the capillary
      electrophoresis system or mass spectrometry system for confirmatory analysis. The
      detection of analytes was achieved by laser-induced fluorescence in capillary
      electrophoresis. Procedures were validated according to the European Union
      regulation 2002/657/EC determining specificity, selectivity and detection
      capability for screening method and decision limit, detection capability,
      specificity, selectivity, trueness and precision for confirmation method. The
      results of validation process demonstrate that the method is suitable for
      application in Brazilian statutory veterinary drug residue surveillance programs.
      Capillary electrophoresis was proved to be a fast, robust method with low time
      and reagents consumption.

PMID- 19765715
TI  - Flow inconsistency: the evil twin of column switching--hardware aspects.
AB  - Solvent flow, generated by HPLC pumps is consistent and accurate. This statement,
      while true for single column (one dimensional) liquid chromatography
      applications, may not apply to column switching applications. Connection of pumps
      and/or columns to one flow path may cause substantial pressure changes. Immediate
      post valve switch pressure differences between pumps can cause backflow where the
      mobile phase stored at higher pressure will temporary flow into the lower
      pressure area. A more common side effect of column switching is flow
      inconsistency during pump pressurization. For the duration of pump
      pressurization, liquid flow through the column will be smaller than expected
      since the HPLC column acts like a flow restrictor.

PMID- 19765716
TI  - Combining microwave-assisted extraction and liquid chromatography-ion-trap mass
      spectrometry for the analysis of hexabromocyclododecane diastereoisomers in
      marine sediments.
AB  - An efficient microwave-assisted extraction (MAE) procedure coupled with high
      performance liquid chromatography-electrospray-ion-trap mass spectrometry (HPLC
      ESI-ITMS) has been evaluated to determine hexabromocyclododecane diastereoisomers
      (alpha-, beta- and gamma-HBCD) in marine sediments. The composition of the LC
      mobile phase (consisting of water, methanol and acetonitrile) and the parameters
      of electrospray ionization (ESI) were evaluated to obtain chromatographic
      baseline separation and high sensitivity for the detection of these
      diastereoisomers. The effects of various operating parameters on the quantitative
      extraction of the HBCDs through MAE were systematically investigated. The three
      diastereoisomers were then quantitated by HPLC-ITMS employing ESI operated in the
      negative ionization mode. The HBCDs were extracted from the sediments through MAE
      using 40mL of acetone/n-hexane (1/3, v/v) at 90 degrees C for 12min. The limits
      of quantitation (LOQ) ranged from 25 to 40pg/g (dry weight) in 5g of the sediment
      samples. The recoveries of the HBCDs in spiked sediment samples ranged from 68 to
      91% (relative standard derivation: 2-11%). The extraction efficiency of the MAE
      technique was also compared with Soxhlet extraction and pressurized liquid
      extraction.

PMID- 19765717
TI  - Identification of free disaccharides and other glycosides in wine.
AB  - Free soluble carbohydrates of different wine samples were analyzed by GC-MS as
      their trimethylsilyloximes using a methylsilicone column. Besides alpha,alpha
      trehalose, several beta-glucosylglucoses such as cellobiose, sophorose,
      laminaribiose and gentiobiose were the main disaccharides identified. With the
      exception of gentiobiose, these disaccharides are now reported for the first time
      in wine. Lactose (4-O-beta-D-galactopyranosyl-D-glucose), previously described in
      this product, was also tentatively identified. Several free glycosides: beta
      ethyl-glucoside and seven glyceryl-glycosides (including glucosides and
      galactosides) were also identified for the first time in wine. On the contrary,
      disaccharides in grape juice were mainly constituted of fructose derivatives,
      including sucrose, and no glycosides were detected. Although the total amount of
      disaccharides was different in white wines (<50mg/L) from those in rose and red
      wines (80-130 mg/L), the chromatographic profile was noticeably similar in all
      wine samples. The method here reported allows the identification of several
      carbohydrates which have not been previously detected in wines and could
      contribute to increase the understanding of enzymatic activity during winemaking.

PMID- 19765718
TI  - Food analysis and foodomics.

PMID- 19765719
TI  - Mesospheres in nano-armor: probing the shape-persistence of molten polymer
      colloids.
AB  - We utilize Brillouin light scattering to investigate the shape-persistence of
      polystyrene-silica core-shell particles by recording their vibrational eigenmodes
      as a function of temperature. The thin silica shell (tens of nm) protects the
      polymer core from changing its spherical shape at temperatures above its glass
      transition temperature Tg, readily obtained from the same experiment. The
      rigidity of the confined core is enhanced compared to the bare core.

PMID- 19765720
TI  - Adsorptive removal of hazardous anionic dye "Congo red" from wastewater using
      waste materials and recovery by desorption.
AB  - The present investigation assesses the applicability of waste materials--bottom
      ash and deoiled soya--for the removal of the colorant Congo red from wastewaters.
      The adsorption characteristics and dye removal efficiency of adsorbents have been
      determined by investigating factors such as effect of pH, effect of concentration
      of the dye, amount of adsorbents, contact time, and temperature. Langmuir,
      Freundlich, Tempkin, and Dubinin-Radushkevich isotherm models have been used to
      evaluate the ongoing adsorption. With the help of adsorption isotherm data
      different thermodynamic parameters such as free energy; enthalpy, and entropy
      have been calculated. The estimated free energy has been obtained as -21.52 kJ
      mol(-1) for bottom ash and -16.88 kJ mol(-1) for deoiled soya. On the basis of
      pseudo-first-order and pseudo-second-order kinetic equations different kinetic
      parameters have been obtained. Column operations depicted good adsorptive
      tendencies for Congo red with 96.95% and 97.14% saturation of dye on bottom ash
      and deoiled soya, respectively. Regeneration of the saturated columns has been
      made by eluting NaOH solution and more than 90% dye has been recovered in both
      cases.

PMID- 19765721
TI  - Anterior cingulate pyramidal neurons display altered dendritic branching in
      depressed suicides.
AB  - BACKGROUND: It is hypothesized that mood disorders are accompanied by altered
      wiring and plasticity in key limbic brain regions such as the anterior cingulate
      cortex (ACC). To test this hypothesis at the cellular level, we analyzed basilar
      dendritic arborizations extended by layer VI pyramidal neurons in silver
      impregnated postmortem ACC samples from well-characterized depressed suicide
      subjects (n=12) and matched sudden-death controls (n=7). METHODS: One cm(3)
      tissue blocks were stained using a Golgi preparation, cut on a microtome, and
      mounted on slides. Basilar dendritic arbors from 195 neurons were reconstructed,
      and the number, length, and diameter of branches were determined at each branch
      order. The size and number of spines borne by these branches were also assessed.
      RESULTS: Third-order branches were significantly reduced in number (24% fewer;
      p=0.00262) in depressed suicides compared to controls. The size and average
      length of these branches, as well as their number of spines/length were
      unaltered. On average, for each pyramidal neuron analyzed in depressed subjects,
      the fewer third-order branches resulted in a significant reduction in branch
      length (28% shorter; p=0.00976) at this branch order. CONCLUSIONS: These results
      provide the first evidence of altered cortical dendritic branching in mood
      disorders. Given that proximal dendritic branches grow during perinatal
      development, and that they are generally less plastic at maturity than distal
      segments, we speculate that these differences in dendritic branching may reflect
      a biological predisposition to depression and suicide.

PMID- 19765722
TI  - Identifying survivors with traumatic craniocervical dissociation: a retrospective
      study.
AB  - BACKGROUND: Traumatic craniocervical dissociation (CCD), which includes atlanto
      occipital dissociation and vertical distraction between C1-C2, is often an
      immediately fatal injury that has increasingly been associated with survival to
      the hospital. Our aim was to identify survivors of CCD based on clinical
      presentation. METHODS: We retrospectively reviewed the Harborview Medical Center
      Trauma Registry and the King County Medical Examiners database from 2001 to 2006.
      Patients>or=12 y old were identified by ICD-9 code, radiographic diagnosis on
      lateral cervical spine films, and CT. We examined age, gender, mechanism of
      injury, presentation and prehospital and hospital interventions, and radiographic
      findings to distinguish survivors and non-survivors. RESULTS: Of 69 patients with
      CCD, 47 were diagnosed post mortem, 22 were diagnosed in hospital, and seven
      survived to discharge. When comparing survivors and non-survivors, age, gender,
      and injury severity score were not significant. Survivors had significantly
      higher GCS, and were more likely to be normotensive; none had cervical cord
      injury; 80% of non-survivors had a basion-dental interval (BDI) of >or=16mm.
      CONCLUSIONS: Trauma patients diagnosed with CCD in the ED, with cervical cord
      injury, requiring CPR, and with GCS of 3 will not survive their injury. Wider BDI
      is associated with mortality.

PMID- 19765723
TI  - Large conductance calcium-activated potassium channels contribute to the reduced
      myogenic tone of peripheral microvasculature after cardiopulmonary bypass.
AB  - BACKGROUND: We investigated the role of calcium-activated potassium (K(Ca))
      channel activation in myogenic tone in human peripheral microvasculature after
      heart surgery. METHODS: Human skeletal muscle arterioles (90-180microm diameter)
      were dissected from tissue harvested pre- and post-cardiopulmonary bypass (CPB)
      during cardiac surgery. Myogenic reactivity in response to stepwise increases in
      intraluminal pressure was studied between pressure steps. Microvessel tone was
      determined pre-CPB, post-CPB, and after blockade of K(Ca) channels. Expression
      and localization of large conductance (BK) K(Ca) channels in the coronary
      microvasculature was assessed by immunoblot and immunofluorescence
      photomicroscopy. RESULTS: Myogenic tone of skeletal muscle arterioles was
      significantly reduced post-CPB compared with pre-CPB. Decrease in myogenic tone
      after CPB was reflected by the increase in microvessel internal diameter.
      Myogenic tone of post-CPB microvessels was significantly increased after
      treatment with BK(Ca)-blocker iberiotoxin, but unchanged in the combined presence
      of the blockers of intermediate (IK(Ca)) and small conductance (SK(Ca)) K(Ca)
      channels, TRAM34/apamin. The increases in myogenic tone after iberiotoxin
      treatment were demonstrated as a decrease in microvessel internal diameter. No
      significant differences in BK(Ca) protein levels were noted comparing pre- and
      post-CPB conditions judged by immunoblot and by immunofluorescence staining of
      skeletal muscle microvessels. Prominent staining for BK(Ca)-alpha and BK(Ca)
      beta(1) subunits localized to the microvascular smooth muscle. CONCLUSION: CPB
      associated decrease in peripheral myogenic reactivity is likely due to activation
      of BK(Ca), but not IK(Ca) or SK(Ca). CPB may increase BK(Ca) activity without
      increasing BK polypeptide level.

PMID- 19765724
TI  - Ethical and legal issues in emergency research: barriers to conducting
      prospective randomized trials in an emergency setting.
AB  - INTRODUCTION: As in any area of medicine, clinical trials are crucial to the
      advancement of trauma care and the establishment of evidence-based guidelines.
      This work identifies consent regulations that impede advances in trauma
      resuscitation research and examines several ethical issues underlying current
      policies in the United States which regulate how clinical trials are conducted in
      an emergency setting. Trauma is a leading cause of mortality in the U.S.
      Minorities and those in low socioeconomic groups are subject to a disproportional
      amount of traumatic injuries and have worse treatment outcomes than non-minority
      individuals. Current regulations guiding consent requirements in emergency
      research were enacted to protect such vulnerable populations from exploitation.
      Ironically, these same regulations also serve as barriers to clinical trials in
      trauma research, thus depriving these same vulnerable groups from the benefits of
      advances in trauma care. METHODS: A literature review was conducted on areas
      affecting emergency medical research including: informed consent, socioeconomic
      and racial disparities, federal regulations in trauma research and biomedical
      ethics. RESULTS: In the ten year period following the passage of the FDA's Common
      Rule (21 CFR 50.24) in 1995, 21 published emergency research studies were
      conducted under the waiver of informed consent. Misconceptions regarding federal
      regulations and cumbersome internal review board approval processes are
      frequently cited as significant barriers to conducting prospective randomized
      trials in the emergency setting. CONCLUSIONS: Given the history of past abuses in
      medical research, the principle of maintaining autonomy of choice is of paramount
      importance. However, trauma resuscitation is unique in that patients are either
      unconscious or of limited mental capacity at the time treatment is required, and
      thus the standard of informed consent is unable to be achieved as in other areas
      of medicine. While this paradox was recognized by the FDA in 1995 with the
      creation of an exception to the requirement for informed consent in emergency
      research (the "Common Rule"), the wording of this exception is ambiguous, and has
      consequently deterred trauma investigators from pursuing valuable research
      endeavors. In particular, the language requiring "community consultation" and
      demonstration that existing treatments are "unproven or unsatisfactory" have been
      identified as the most problematic terms to satisfactorily address by those
      aiming to conduct trauma research. It is imperative that the current exemptions
      to the Common Rule be more thoroughly operationalized, so that greater
      advancement in emergency medicine research can be promulgated, while concurrently
      maintaining a high standard of protection for the rights of trauma patients.

PMID- 19765725
TI  - Significance of M2-polarized tumor-associated macrophage in pancreatic cancer.
AB  - BACKGROUND: The roles of infiltrating macrophages within the tumor
      microenvironment are complex because of their functional variety. The aim of this
      study is to examine the role and prognostic significance of tumor-associated
      macrophages (TAMs) that have an M2 polarized function in pancreatic cancer.
      MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded blocks were obtained
      from 76 patients with pancreatic head cancer. All patients underwent macroscopic
      curative resection. We assessed the number of infiltrating macrophages within the
      tumor invasive front by not only CD68 but also by CD163 and CD204, which are
      specific receptors on M2-polarized macrophages. Furthermore, to evaluate
      lymphangiogenesis, we measured the density of lymphatic vessels in the tumor
      invasive front by using D2-40. RESULTS: High incidence of lymph node metastasis
      was shown in cases with a high number of CD163- or CD204-positive macrophages.
      Significantly increased lymphatic vessel density (LVD) was shown in cases with
      lymph node metastasis compared with cases without lymph node metastasis
      (P=0.0094). Significantly increased LVD (P=0.0175) and a poor prognosis
      (P=0.0171) were shown in cases with a high number of macrophages that express
      CD163 or CD204, however, there was no significant difference according to the
      number of CD68-positive macrophages. CONCLUSIONS: M2-polarized TAMs in the
      invasive front of pancreatic cancer are associated with a poor prognosis due to
      accelerated lymphatic metastasis, and inhibition of the functional interaction
      between M2-polarized TAMs and tumor cells may improve the prognosis.

PMID- 19765726
TI  - Multiple genetic alterations in papillary thyroid cancer are associated with
      younger age at presentation.
AB  - BACKGROUND: There is a significant gender and age disparity in thyroid cancer
      incidence and outcome. The molecular basis for these divergent clinical
      presentations and outcome are essentially unknown. METHODS: The primary tumor
      genotype in 217 patients with papillary thyroid cancer was determined for six
      common somatic genetic alterations (RET/PTC1, RET/PTC3, and NTRK1 rearrangements,
      and BRAF V600E, KRAS, and NRAS hotspot mutations) by PCR and direct sequencing,
      and nested PCR. Univariate and multivariate analyses were performed to determine
      the association of genetic changes and age, gender, and other clinicopathologic
      factors. RESULTS: One hundred twenty-one of the 190 conventional papillary
      thyroid carcinoma samples (63.7%) had at least one genetic alteration, and 27 of
      the samples (14.2%) had more than one alteration. In the follicular variant of
      papillary thyroid carcinomas, 13 of the 27 samples (48.1%) had at least one
      genetic alteration and three of the 27 samples (11.1%) had more than one. The
      presence of multiple genetic alterations was associated with younger age at
      diagnosis (P=0.034), mean difference of 8 y earlier. We found no significant
      association with the number or type of genetic alterations present by gender,
      tumor size, extent of tumor differentiation, multicentricity, lymph node
      metastasis, distant metastases, TNM stage, and the AMES risk group. The
      association of multiple genetic alterations and younger age were independent of
      tumor size, lymph node or distant metastasis, TNM stage, or AMES risk group.
      CONCLUSIONS: Multiple genetic alterations are more common in younger patients
      with papillary thyroid cancer, but there is no difference in the type or number
      of genetic alterations by gender. Our findings suggest that multiple genetic
      alterations in thyroid cancer may be associated with earlier disease initiation
      and or progression.

PMID- 19765727
TI  - Hyperkalemia following massive transfusion in trauma.
AB  - BACKGROUND: Large-volume blood transfusions have been implicated in the
      development of hyperkalemia. The purpose of the current study was to determine
      whether critically injured patients receiving massive transfusions are at an
      increased risk of hyperkalemia. METHODS: Massive transfusion (MT) cohort, all
      trauma patients (02/2004-01/2008) taken directly to the OR and receiving >or=10
      units of RBC in first 24h. Comparison cohort (No-RBC), all patients (02/2004
      01/2008) transported directly to the OR who received no blood products in the
      first 24h. Hyperkalemia defined as K+ > 5.5 mEq/L. RESULTS: There were 266 MT
      patients, 237 No-RBC patients. MT patients were more likely to have hyperkalemia
      in the immediate postoperative setting (1.8% versus 4.6%, P = 0.049). However,
      linear regression did not identify intraoperative blood transfusions as a
      predictor of postoperative K+ values (P = 0.417). Logistic regression identified
      only preop K+ (OR 1.79, P = 0.021) and postop pH (OR 0.009, P = 0.001), but not
      MT, as independent risk factors for postop hyperkalemia. CONCLUSIONS: Despite
      concerns of hyperkalemia following MT, we found less than a 5% incidence of
      postop K+ (>5.5 mEq/L). After adjusting for the significant effects of preop K+
      and postop pH, MT patients were at no higher risk of hyperkalemia than those who
      received no blood products.

PMID- 19765728
TI  - Pediatric solid tumors and second malignancies: characteristics and survival
      outcomes.
AB  - BACKGROUND: To examine the incidence, characteristics, and outcomes for second
      malignancies following the diagnosis of a primary solid tumor in pediatric
      patients. METHODS: The Surveillance, Epidemiology, and End Results (SEER)
      database was queried from 1973 to 2005, excluding recurrences, in patients <20 y.
      RESULTS: A total of 31,685 cases of pediatric solid malignancies were identified.
      Overall, 177 patients were diagnosed with a unique second malignancy before the
      age 20 (0.56%) The mean follow-up was for 8.5 y (2 mo-30.8 y). Mean age at
      diagnosis of the primary tumor was 7.7 y. The most common primary malignancies
      were CNS tumors (22.5%), followed by soft tissue sarcoma (15.8%), retinoblastoma
      (14.1%), and bone tumors (13%). Hematologic malignancies (35.5%) were the most
      common second malignancies noted in the cohort, followed by bone tumors (18%) and
      soft tissue sarcomas (15%). Hematologic malignancies had a shorter latency (3.1
      y) compared with solid second tumors (11.6 y). The overall 10-y survival for the
      entire cohort was 41.5%. For most tumor categories, development of a secondary
      malignancy was associated with lower 5- and 10-y survival than expected.
      CONCLUSIONS: CNS tumors, retinoblastoma, and soft tissue sarcomas in children are
      the most common solid primary tumors, with an increased risk of a second
      malignancy. Leukemia is the most common second malignancy seen in pediatric solid
      tumors. Second malignancies are associated with significantly reduced survival
      rates compared with the general childhood cancer population.

PMID- 19765729
TI  - COX-2 inhibition improves immune system homeostasis and decreases liver damage in
      septic rats.
AB  - OBJECTIVE: To evaluate cyclooxygenase-2 (COX-2) inhibition by NS-398 in septic
      rats with respect to immunologic derangements and hepatic damage. METHODS: Six
      sham rats (Sham), 24 rats that underwent experimentally induced sepsis using
      cecal ligation and puncture (CLP), and 24 rats that underwent induced sepsis
      after treatment with NS-398 (NS-398), were compared. Sham rats were immediately
      sacrificed. Six each of CLP and NS-398 animals were sacrificed at 3, 6, 12, and
      24 h after induction of sepsis. From each rat was obtained liver for COX-2 mRNA
      copy number determination and blood for quantification of alanine transaminase
      (ALT), aspartate aminotransferase (AST), interleukin 10 (IL-10), interleukin 6
      (IL-6), and tumor necrosis factor alpha (TNFalpha) levels, and CD4:CD8 ratios.
      RESULT: Sham rats had a lower COX-2 mRNA copy number than NS-398 rats, which had
      a lower copy number than CLP rats. CLP and NS-938 rats had IL-10 and IL-6 levels
      above Sham levels. NS-938 rat IL-10 levels were greater and IL-6 levels less than
      those of CLP rats. For CLP rats, TNF production sharply declined and then
      increased above Sham levels; NS-398 rat TNF production was consistently mildly
      elevated above Sham levels. CD4:CD8 ratios sharply dropped over time; NS-398
      showed a more modest decline. CLP rats showed unrelenting climbs in AST and ALT
      values; NS-398 rat levels peaked at 6 h and returned to normal after 12 h; the
      biochemical evidence of protection against septic liver damage was also seen
      morphologically, with ultrastructural and histologic normalization of nuclear
      appearances 12 h after sepsis induction with NS-398 pretreatment. CONCLUSION:
      Septic rats given the COX-2 inhibitor NS-398 showed amelioration of cytokine and
      cellular immunologic imbalances and decreased liver injury.

PMID- 19765730
TI  - Down-regulation of c-Met expression inhibits human HCC cells growth and invasion
      by RNA interference.
AB  - BACKGROUND: Cell migration is a basis for invasion and metastasis of malignant
      tumors. Receptor tyrosine kinases are recognized as important therapeutic targets
      in antineoplastic strategies. C-met is a receptor tyrosine kinase highly
      expressed in human hepatocellular carcinoma (HCC) cell line MHCC97-H. Higher
      expression of c-met in tumor tissue can lead to scattering, angiogenesis,
      proliferation, enhanced cell motility, invasion, and eventually, metastasis. To
      explore the roles of c-met in modulating the motility of cell, we silenced c-met
      expression in the HCC line MHCC97-H by RNA interference (RNAi). MATERIALS AND
      METHODS: For transient expression, c-met-siRNA 1,2 recombinant plasmids were
      transfected into phoenix A cells. The MHCC97-H cells were cultured in Dulbecco's
      modified Eagles's medium (DMEM) with 10% fetal bovine serum (FBS) to establish
      MHCC97-H HCC cells stably expressing c-met-siRNA. MHCC97-H cells were treated
      with the recombinant virus for assay of c-met mRNA and protein, evaluation of
      growth and invasion of MHCC97-H cells, and identification of hepatitis B virus X
      (HBX) protein correlation with c-met. RESULTS: After transfection of c-met-siRNA
      for 48 h, the expression of c-met decreased markedly in MHCC97-H cells; the most
      effective site of the siRNA target sequence is at the 537 upstream, far from the
      transcription start. In addition, the proliferation, motility, and invasive
      ability of MHCC97-H cells were significantly inhibited. Furthermore, we showed
      that hepatitis B virus (HBV) X protein (HBX) potentiated the activities of the
      extracellular signal-regulated kinase 1/2 (ERK1/2) in MHCC97-H cells. Treatment
      with extracellular signal-regulated kinase (ERK) inhibitor (U0126), but not P38
      MAPK inhibitor (SB203580) or phosphatidylinositol 3-kinase (PI3K) inhibitor
      (wortmannin), markedly suppressed the expression of c-met protein in MHCC97-H
      cells. CONCLUSION: These results indicate that the over-expression of c-met
      protein plays an important role in the cell invasion of MHCC97-H, and HBX protein
      may promote the expression of c-met by ERKs pathway.

PMID- 19765731
TI  - Can harmonic focus curved shear effectively seal the pancreatic ducts and prevent
      pancreatic leak? Feasibility evaluation and testing in ex vivo and in vivo
      porcine models.
AB  - BACKGROUND: The purpose of this study was to evaluate the ability of Harmonic
      energy technology to transect and seal the pancreatic duct compared with the
      standard monopolar electrosurgery transection and oversew technique in a porcine
      distal pancreatectomy survival model. Harmonic energy technology is as effective
      as standard oversew technique for preventing pancreatic leak after distal
      pancreatectomy. METHODS: The animal protocol used for this study was approved by
      the Institutional Animal Care and Use Committee (IACUC) prior to the conduct of
      the study. Spleen-preserving distal pancreatectomy was performed in seven pigs
      (80-100 lb) by the same surgeon. In four animals, the pancreas was divided with
      the Harmonic Focus Curved Shears (test group) with no additional suturing for
      control of hemostasis or leak. In three animals, the pancreas was divided using
      monopolar electrosurgery (30 W coagulation) and the cut end of the pancreas was
      oversewn with a locking suture (control group). A previously worked out standard
      operative technique was used in all procedures. Operating end points included
      surgery time and blood loss. Animals were euthanized and necropsied at 7 to 8 d
      following surgery. Survival endpoints included clinical response to surgery,
      serum chemistry profiles before surgery and at necropsy, and histology of the
      pancreas transection site. RESULTS: Mean operative time for pancreatic resection
      was 15min in the control group and 10min in the test group. No significant blood
      loss was noted in either group. The median size of the resected pancreas was 4.3
      cm. Three animals in the control group and three in the test group completed the
      study without complications. One animal in the test group failed to eat, appeared
      dehydrated, and was taken off study on POD#2. In this animal, there was a
      doubling of serum lipase at euthanasia and gross evidence of ileus, which was
      attributed to a pancreatic leak. Histologic examination of the residual pancreas
      in both groups at necropsy revealed a 2-5 mm band of necrotic tissue associated
      with neutrophilic infiltration in the control group, and less than a 1mm band of
      necrotic tissue in the test group. CONCLUSION: The Harmonic Focus Curved Shears,
      using Harmonic energy technology, appears to seal the pancreatic ducts and
      prevent pancreatic leak at 75% (3/4) efficiency in this survival model. However,
      the survival leak rate, 25% (1/4) was higher in the Harmonic Focus Curved Shears
      test group compared with the control oversewn group 0% (0/3). This feasibility
      study shows potential for Harmonic technology to be used to seal the pancreatic
      ducts, but additional testing and optimization of surgical techniques are needed.

PMID- 19765732
TI  - Malignant intraductal papillary mucinous neoplasm: are we doing the right thing?
AB  - BACKGROUND: Because of the malignant potential, resection has been recommended
      for some intraductal papillary mucinous neoplasms (IPMN). We hypothesize that a
      large cancer database could be used to evaluate national resection rates and
      survival for malignant IPMN. MATERIALS AND METHODS: Using the Surveillance
      Epidemiology and End Results (SEER) database, 1988-2003, cases of malignant IPMN
      were identified using histology codes. Age-adjusted incidence rates were
      calculated; Cochran-Armitage tests evaluated trends over time. Predictors of
      resection were evaluated using chi(2) and logistic regression. Kaplan-Meier
      curves and Cox models were constructed to evaluate survival. RESULTS: Of 1834
      patients, 209 (11.4%) underwent resection. Annual age-adjusted incidence
      decreased over the study time-course (P<0.05), while annual proportion of
      patients presenting with localized lesions and the proportion being resected
      increased (P<0.05). Predictors of resection on multivariate analysis included
      localized stage [versus distant, adjusted odds ratio (OR) 31; 95% confidence
      interval (CI) 17-56], and more recent diagnosis [referent 1988-1991; 2000-2003,
      OR 3.0 (95%CI 1.7-5.3)]. Median survival for resected patients was 16 mo versus 3
      mo without resection (P<0.0001). After adjusting for age, gender, stage, year,
      and tumor location, surgical resection remained a significant predictor of
      survival [hazard ratio 0.44 (95% CI 0.36-0.54), P<0.0001]. CONCLUSIONS: In this
      population-based cohort, detection of malignant IPMNs is decreasing, with an
      increasing proportion of patients diagnosed at local stages and undergoing
      resection. Increased awareness of IPMN may be contributing to earlier detection,
      which might include benign/premalignant lesions, and greater utilization of
      resection for appropriate candidates; thus, we may be improving survival for this
      most treatable form of pancreatic cancer.

PMID- 19765733
TI  - Identification of a novel potential biomarker in a model of hemorrhagic shock and
      valproic acid treatment.
AB  - BACKGROUND: The initial management of a poly-trauma patient requires evaluation
      for potential hemorrhage and ongoing monitoring to assess the efficacy of
      treatment and avoid complications related to massive blood loss. Certain serum
      protein levels may be altered in response to hemorrhagic shock, and may serve as
      useful biomarkers to guide diagnosis, prognosis, and therapeutics in traumatic
      hemorrhagic shock (HS). Treatment with valproic acid (VPA) has been shown to up
      regulate various survival pathways and improve outcome. Here we determine whether
      these changes would result in altered serum biomarkers. METHODS: Wistar-Kyoto
      rats underwent hemorrhagic shock (60% blood loss) followed by treatment with or
      without VPA (300 mg/kg). Using surface enhanced laser desorption-time of flight
      mass spectrometry (SELDI or SELDI-TOF MS) technology, we screened serum samples
      obtained from five rats at different time points (baseline, post-hemorrhagic
      shock, and post-VPA treatment) in a lethal model of hemorrhagic shock (HS).
      Additionally, we used isobaric tag labeling for relative quantitation (iTRAQ) to
      identify potential biomarkers in the serum. Western blots were performed to
      validate iTRAQ-identified biomarker from independent serum samples, and to
      analyze protein biomarker levels in the intestine during hemorrhagic shock and
      treatment. RESULTS: HS and treatment with VPA affected serum levels of many
      proteins. One such protein with a mass spectrum around 22.7 kDa was detected in
      all five rats. The same serum samples subjected to iTRAQ resulted in our
      identification of claudin-3, a 23 kDa tight junction protein. HS elevated serum
      claudin-3 protein levels, which was reversed by VPA treatment in a pattern
      similar to the SELDI-TOF MS studies. Further validation with independent serum
      and intestine samples from individual rats by Western blots confirmed that HS
      increased the protein level of claudin-3 in serum and decreased its level in the
      intestine. Treatment with VPA reversed the hemorrhagic shock-induced alteration
      in claudin-3 to sham levels. CONCLUSIONS: HS causes an acute rise in serum
      claudin-3 protein levels and a concurrent decrease in intestinal claudin-3
      protein expression. VPA treatment attenuates these alterations and stabilizes
      intestinal claudin-3 levels. Our results demonstrate for the first time that
      claudin-3 is a potential biomarker in HS and treatment.

PMID- 19765734
TI  - Further uses of gastrografin in adhesive small bowel obstruction: are we close to
      a definitive answer.

PMID- 19765735
TI  - MG-132 inhibits carcinoid growth and alters the neuroendocrine phenotype.
AB  - BACKGROUND: Carcinoid cancers are the most common neuroendocrine (NE) tumors, and
      limited treatment options exist. The inhibition of glycogen synthase kinase-3beta
      (GSK-3beta) has been shown to be a potential therapeutic target for the treatment
      of carcinoid disease. In this study, we investigate the ability of MG-132, a
      proteasome inhibitor, to inhibit carcinoid growth, the neuroendocrine phenotype,
      and its association with GSK-3beta. MATERIALS AND METHODS: Human pulmonary (NCI
      H727) and gastrointestinal (BON) carcinoid cells were treated with MG-132 (0
      4microM). Cellular growth was measured by the 3-[4,5-dimethylthiazole-2-yl]-2,5
      diphenyl tetrazolium bromide (MTT) assay. Levels of total and phosphorylated GSK
      3beta and the NE markers chromogranin A (CgA), Achaete-Scute complex-like 1
      (ASCL1), as well as the apoptotic markers poly (ADP-ribose), polymerase (PARP),
      and cleaved caspase-3 were determined by Western blot. RESULTS: Treating
      carcinoid cells with MG-132 resulted in growth inhibition, a dose-dependent
      inhibition of CgA and ASCL1, as well as an increase in the levels of cleaved PARP
      and cleaved caspase-3. Additionally, an increase in the level of phosphorylated
      GSK-3beta was observed. CONCLUSION: MG-132 inhibits cellular growth and the
      neuroendocrine phenotype. This proteasome inhibitor warrants further preclinical
      investigation as a possible therapeutic strategy for intractable carcinoid
      disease.

PMID- 19765736
TI  - Exact CT-based liver volume calculation including nonmetabolic liver tissue in
      three-dimensional liver reconstruction.
AB  - Exact preoperative determination of the liver volume is of great importance prior
      to hepatobiliary surgery, especially in living donated liver transplantation
      (LDLT) and extended hepatic resections. Modern surgery-planning systems estimate
      these volumes from segmented image data. In an experimental porcine study, our
      aim was (1) to analyze and compare three volume measurement algorithms to predict
      total liver volume, and (2) to determine vessel tree volumes equivalent to
      nonmetabolic liver tissue. Twelve porcine livers were examined using a
      standardized three-phase computed tomography (CT) scan and liver volume was
      calculated computer-assisted with the three different algorithms. After
      hepatectomy, livers were weighed and their vascular system plasticized followed
      by CT scan, CT reconstruction and re-evaluation of total liver and vessel volumes
      with the three different algorithms. Blood volume determined by the plasticized
      model was at least 1.89 times higher than calculated by multislice CT scans (9.7%
      versus 21.36%, P=0.028). Analysis of 3D-CT-volumetry showed good correlation
      between the actual and the calculated liver volume in all tested algorithms with
      a high significant difference in estimating the liver volume between Heymsfield
      versus Heidelberg (P=0.0005) and literature versus Heidelberg (P=0.0060). The
      Heidelberg algorithm reduced the measuring error with deviations of only 1.2%.
      The present results suggest a safe and highly predictable use of 3D-volumetry in
      liver surgery for evaluating liver volumes. With a precise algorithm, the volume
      of remaining liver or single segments can be evaluated exactly and potential
      operative risks can therefore be better calculated. To our knowledge, this study
      implies for the first time a blood pool, which corresponds to nonmetabolic liver
      tissue, of more than 20% of the whole liver volume.

PMID- 19765737
TI  - Non-motor functions in parkinsonian patients implanted in the pedunculopontine
      nucleus: focus on sleep and cognitive domains.
AB  - Between 2005 and 2007, six patients affected by idiopathic Parkinson's disease
      (IPD) were submitted to the bilateral implantation (and subsequent deep brain
      stimulation - DBS) of the pedunculopontine nucleus (PPN) plus the subthalamic
      nucleus (STN). This review synthesizes the effects of PPN low-frequency
      stimulation on non-motor functions, focusing on patient sleep quality and
      cognitive performance. If not associated to STN-DBS, PPN-DBS promoted a modest
      amelioration of patient motor performance. However, during PPN-DBS, they
      experienced on the one hand a significant improvement in executive functions and
      working memory, on the other hand a beneficial change in sleep architecture.
      Overall, the limited sample hampers definite conclusions. Yet, although the PPN
      DBS induced motor effects are quite disappointing (discouraging extended trials
      based upon the sole PPN implantation), the neuropsychological profile supports
      the contention by which in selected PD patients, with subtle cognitive deficits
      or vanished efficacy of previous implanted STN, PPN-DBS might still represent a
      reliable and compassionate option.

PMID- 19765739
TI  - Survival after transapical and transfemoral aortic valve implantation: talking
      about two different patient populations.
AB  - OBJECTIVE: Recently, suspicion had been expressed that survival might be impaired
      after antegrade transapical as opposed to retrograde transfemoral valve
      implantation in high-risk patients with aortic stenosis. We analyzed survival in
      patients undergoing transcatheter aortic valve implantation with special emphasis
      on the access site for implantation. METHODS: Between June 2007 and February
      2009, 203 high-risk patients (EuroSCORE, 22% +/- 14%; mean age, 81 +/- 7 years)
      underwent transcatheter aortic valve implantation via a transapical (n = 50) or
      transfemoral (n = 153) access. The transapical implantation technique was chosen
      only in patients who had no access through diseased femoral arteries. RESULTS:
      Thirty-day survival was 88.8% after transfemoral versus 91.7% after transapical
      implantation (P = .918). The transapical group had a significantly higher
      preoperative brain natriuretic peptide value and a significantly higher incidence
      of peripheral vessel, cerebrovascular, and coronary heart disease. Death within
      30 days was valve related in 25% (transapical) and 31% (transfemoral), cardiac in
      25% and 13%, and noncardiac in 50% and 56%, respectively (no significant
      difference). Complications specific to the access site (peripheral vessel injury
      or apex complications) occurred in both groups, whereas neurologic events did not
      occur in the transapical group (P = .041). CONCLUSIONS: Our patient and access
      site selection process, with the transfemoral technique considered the access
      site of first choice, results in comparable survival and morbidity for either
      transfemoral or transapical transcatheter aortic valve implantation. Both
      techniques are associated with certain access site-specific complications that
      require highly qualified management. The neurologic risk profile of the patients
      should be included in the decision-making process before transcatheter aortic
      valve implantation, inasmuch as neurologic events may be reduced with the
      transapical access.

PMID- 19765740
TI  - Is prophylactic treatment of contralateral blebs in patients with primary
      spontaneous pneumothorax indicated?
AB  - OBJECTIVES: More than 50% of patients with primary spontaneous pneumothorax have
      contralateral blebs/bullae, and about a quarter will develop a contralateral
      pneumothorax. The purpose of this prospective study was to determine the need for
      elective treatment of asymptomatic contralateral blebs/bullae in patients
      presenting with primary spontaneous pneumothorax. METHODS: From May 2006 through
      June 2008, results from 35 patients with ipsilateral primary spontaneous
      pneumothorax without contralateral blebs receiving unilateral video-assisted
      thoracic surgery, 35 patients with ipsilateral primary spontaneous pneumothorax
      with contralateral blebs receiving unilateral video-assisted thoracic surgery,
      and 16 patients with ipsilateral primary spontaneous pneumothorax receiving
      bilateral video-assisted thoracic surgery for positive contralateral blebs were
      collected. Their demographic and operating data were also recorded. RESULTS:
      There was no significant difference in age, gender, smoking percentage, body mass
      index (kg/m(2)), blood loss, and postoperative pain among groups. There was
      longer operative time and length of stay in group receiving bilateral surgery.
      Within the follow-up period of 16.68 +/- 9.91 months (median, 17.50), no
      recurrence on either lung was found in the group operated on both sides, while
      contralateral occurrence was found in 17.14% of the group with ipsilateral
      primary spontaneous pneumothorax with contralateral blebs receiving unilateral
      video-assisted thoracic surgery within the period of 18.15 +/- 8.07 months
      (median, 21). CONCLUSION: The study showed that the preemptive video-assisted
      thoracic surgery for the contralateral blebs/bullae effectively prevented the
      contralateral occurrence.

PMID- 19765741
TI  - The impact on survival of positive intraoperative pleural lavage cytology in
      patients with non-small-cell lung cancer.
AB  - OBJECTIVE: The aim of this study was to analyze intraoperative pleural lavage
      cytology results in patients with non-small-cell lung cancer and quantify the
      impact on survival and recurrence. METHODS: From August 1992 through November
      2006, pleural lavage cytology results before and after lung resection were both
      available in 2178 patients with non-small-cell lung cancer. We assessed the pre
      pleural lavage cytology impact on survival, comparing with 9 factors available
      before lung resection by multivariate analyses. We also compared the impact with
      that of pleural dissemination or malignant pleural effusion. For post-pleural
      lavage cytology, we analyzed its survival impact in relation with 15
      clinicopathologic factors, including those available after resection, by
      multivariate analyses. RESULTS: Pre-pleural lavage cytology proved to be a strong
      independent prognostic factor, but the 5-year survival rate was 37% in 65
      patients without dissemination but with a positive pre-pleural lavage cytology,
      which was significantly higher than 12% in 86 patients with dissemination. When
      factors available after resection were combined, post-pleural lavage cytology
      showed a stronger survival impact than pre-pleural lavage cytology. Post-pleural
      lavage cytology was also a strong predictor of recurrence. The positive post
      pleural lavage cytology group had a marginally, but not significantly, better
      survival compared with the malignant pleural effusion group. Almost all patients
      with positive post-pleural lavage cytology relapsed within 5 years. CONCLUSIONS:
      Pre-pleural lavage cytology is of less use in clinical practice. Post-pleural
      lavage cytology was a very strong independent prognostic factor, and almost all
      patients with positive post-pleural lavage cytology relapsed within 5 years. We
      propose that positive post-pleural lavage cytology disease should be classified
      to pathologic T4 and managed similarly to dissemination.

PMID- 19765742
TI  - Differences in initial benign prostatic hyperplasia management between primary
      care physicians and urologists.
AB  - PURPOSE: The introduction of efficacious pharmacotherapies has effectively
      transformed benign prostatic hyperplasia into a chronic disease that requires
      ongoing medical care. With this transformation primary care physicians have
      become more involved in the management of benign prostatic hyperplasia. The
      impact of the increasing role of the primary care physician on the use of benign
      prostatic hyperplasia related health services remains unknown. MATERIALS AND
      METHODS: We performed a retrospective cohort study using medical claims from a
      nonprofit managed care organization. Between 1997 and 2005 we identified incident
      cases of benign prostatic hyperplasia and the provider responsible for the
      initial care. We fitted logistic regression models to measure the association
      between subject receipt of an evaluative process and the treating physician
      specialty. Furthermore, we examined differences between primary care physicians
      and urologists with respect to the use of medical therapy. RESULTS: Less than a
      third of incident cases received initial care from a urologist. Use of office
      based procedures and urodynamic tests was exclusive to urology. Urologists
      performed urinalysis testing and transrectal ultrasonography more frequently than
      primary care physicians (p <0.001). The odds of having a laboratory study doubled
      with treatment by a urologist (OR 2.03, 95% CI 1.51-2.74). Men seen by a
      urologist were also more likely to be prescribed a benign prostatic hyperplasia
      medication (p <0.001). Among those who received medical therapy, prescription of
      selective alpha-adrenergic blockers, 5alpha-reductase inhibitors and combination
      therapy was higher among urologists (p = 0.002). CONCLUSIONS: On average,
      urologists had a higher intensity practice style for benign prostatic hyperplasia
      than primary care physicians. Further studies are needed to determine how these
      practice style differences relate to patient clinical outcomes.

PMID- 19765743
TI  - Open versus laparoscopic staged Fowler-Stephens orchiopexy: impact of long loop
      vas.
AB  - PURPOSE: There is a paucity of literature on factors associated with testicular
      atrophy following second stage laparoscopic Fowler-Stephens orchiopexy. We
      hypothesized that dissection of a long looping vas during this procedure could
      compromise testicular blood supply, leading to testicular atrophy. MATERIALS AND
      METHODS: Following an initial laparoscopic testicular vessel ligation, a second
      stage Fowler-Stephens orchiopexy was performed in 73 testes (laparoscopic in 61,
      open in 12). The presence of a long looping vas was noted from the first stage
      operative notes. Doppler ultrasound was performed postoperatively to confirm
      testicular atrophy. RESULTS: Atrophy rate at a mean followup of 13.5 months was
      20.5% (15 of 61 in laparoscopic and 0 of 12 in open orchiopexy). None of the 5
      long looping vas testes atrophied following open orchiopexy, compared to 5 of 6
      (83%) following laparoscopic orchiopexy (p = 0.03). Analyzing the laparoscopic
      group alone, a long looping vas was significantly associated with risk of atrophy
      (p <0.01). CONCLUSIONS: The presence of a long looping vas was associated with a
      higher atrophy rate following laparoscopic second stage Fowler-Stephens
      orchiopexy. Laparoscopic management of the long looping vas may be more
      challenging and, therefore, in such cases open Fowler-Stephens orchiopexy may
      result in better success rates by preserving the integrity of the collateral
      vessels.

PMID- 19765744
TI  - Alterations in caveolin expression and ultrastructure after bladder smooth muscle
      hypertrophy.
AB  - PURPOSE: Partial bladder outlet obstruction in male rabbits causes detrusor
      smooth muscle hypertrophy and voiding dysfunction similar to that observed in men
      with benign prostate hyperplasia. Using this model, we analyzed the protein
      expression and ultrastructure of caveolae and the intermediate size filament in
      detrusor smooth muscle following partial bladder outlet obstruction induced
      hypertrophy. MATERIALS AND METHODS: Detrusor smooth muscle sections from bladder
      body were processed for immunofluorescence and electron microscopy. Western
      analysis was performed to determine the expression of caveolin isoform-1, 2 and
      3, and intermediate size filament proteins. RESULTS: Detrusor smooth muscle cells
      from both normal and hypertrophied bladders contain orderly arrays of thick and
      thin myofilaments, interspersed with dense bodies. In addition, there was an
      increase in intermediate size filaments in the hypertrophic detrusor smooth
      muscle cells. The dense plaques in the inner membrane of hypertrophied detrusor
      smooth muscle were longer than those of the control. Detrusor smooth muscle from
      hypertrophied bladder revealed a decreased number of caveolae and a lack of their
      orderly distribution at the plasma membrane. Western blotting showed decreased
      expression of caveolin-1, 2 and 3 in hypertrophied detrusor smooth muscle.
      CONCLUSIONS: Caveolae serve as platforms for proteins and receptors that have a
      role in signal transduction. The decreased number of caveolae and caveolin
      protein expression in hypertrophied detrusor smooth muscle might contribute to
      alterations in signal transduction pathways that regulate the downstream effects
      of agonist induced contraction, including calcium sensitization, observed in
      obstructed bladder. In addition, the increased number of intermediate size
      filaments in the hypertrophied detrusor smooth muscle is likely to alter the
      cytoskeletal structure and affect the cellular transmission of passive and/or
      active force.

PMID- 19765746
TI  - Predictive factors for vesicoureteral reflux and prenatally diagnosed renal
      pelvic dilatation.
AB  - PURPOSE: We sought to identify predictive factors for primary vesicoureteral
      reflux among infants with prenatally detected renal pelvic dilatation. MATERIALS
      AND METHODS: A total of 250 neonates were diagnosed with isolated renal pelvic
      dilatation between 1999 and 2008, and followed prospectively. The main event of
      interest was presence of moderate to severe reflux (grade III to V). Diagnostic
      odds ratio, sensitivity, specificity, and diagnostic accuracy (assessed by AUC)
      of fetal and postnatal renal pelvic dilatation were determined. Severity of
      dilatation was classified by Society for Fetal Urology grade. Binary logistic
      regression was performed to identify variables significantly associated with
      vesicoureteral reflux. RESULTS: A total of 23 patients (9.2%) had primary
      vesicoureteral reflux, of whom 16 had grade III to V disease. Diagnostic accuracy
      was 0.70 (95% CI 0.63 to 0.75) for fetal and 0.65 (95% CI 0.59 to 0.71) for
      postnatal renal pelvic dilatation. Combined results of fetal and postnatal renal
      pelvic dilatation were also assessed. When both tests less than 10 mm were
      considered negative indicators of moderate to severe vesicoureteral reflux
      sensitivity increased to 97% and diagnostic odds ratio to 19.1. After adjustment
      by logistic regression only Society for Fetal Urology grade greater than I and
      ureteral dilatation were variables independently associated with grade III to V
      reflux. CONCLUSIONS: Fetal and postnatal renal pelvic dilatation was a poor
      predictor of vesicoureteral reflux. Nevertheless, diagnostic accuracy regarding
      clinically significant vesicoureteral reflux improved when fetal and postnatal
      renal pelvic dilatation less than 10 mm was considered a negative indicator of
      reflux.

PMID- 19765748
TI  - Hematuria: the presenting symptom of an angiosarcoma of the inferior vena cava.

PMID- 19765750
TI  - Editorial comment.

PMID- 19765752
TI  - Renal epithelioid angiomyolipoma.

PMID- 19765754
TI  - T-cell recognition of prostatic peptides in men with chronic prostatitis/chronic
      pelvic pain syndrome.
AB  - PURPOSE: A potential etiology of chronic prostatitis/chronic pelvic pain syndrome
      is autoimmunity. We determined whether T cells from men with chronic
      prostatitis/chronic pelvic pain syndrome would recognize peptides derived from
      the normal self-prostatic proteins prostate specific antigen and prostatic acid
      phosphatase. MATERIALS AND METHODS: CD4 T cells purified from peripheral blood of
      31 patients with chronic prostatitis/chronic pelvic pain syndrome and from the
      buffy coat preparation of 27 normal male blood donors were stimulated in vitro
      with a panel of immunogenic peptides from prostate specific antigen and prostatic
      acid phosphatase, and assayed for reactivity with the peptides by interferon
      gamma enzyme-linked immunosorbent spot assay. Intermediate resolution HLA typing
      was done by polymerase chain reaction. Peptides were also tested by binding assay
      against different class II alleles. RESULTS: Peptide PAP(173-192) was recognized
      more frequently by CD4 T cells from patients with chronic prostatitis/chronic
      pelvic pain syndrome than from healthy donors. The recognition of prostate
      specific antigen peptides was not statistically different when comparing cases to
      normal male blood donors individually. Peptide reactivity was more common in
      patients than in normal male blood donors for any prostate specific antigen
      peptide or any tested peptide. All peptides showed high promiscuity on binding
      assays. There was no association of cases with any specific HLA class II
      phenotype at intermediate resolution. CONCLUSIONS: CD4 T cells from patients with
      chronic prostatitis/chronic pelvic pain syndrome have a higher rate of
      recognizing the self-prostatic proteins prostatic acid phosphatase and prostate
      specific antigen compared to those from normal male blood donors. Data provide
      further evidence to support the role of autoimmunity in some men with chronic
      prostatitis/chronic pelvic pain syndrome.

PMID- 19765755
TI  - Pediatric pyeloplasty: comparison of literature meta-analysis of laparoscopic and
      open techniques with open surgery at a single institution.
AB  - PURPOSE: We performed a meta-analysis of published series of laparoscopic and
      open pyeloplasty. We compared these data to open pyeloplasty at our institution
      using diuretic renography as the indicator for obstruction and postoperative
      success. MATERIALS AND METHODS: Laparoscopic studies included 19 series published
      between 1995 and 2007 comprising 346 kidneys. Open pyeloplasty studies included 9
      series published between 1998 and 2007 comprising 486 kidneys. Data from our
      institution included records for 213 patients (224 kidneys). We defined
      reoperative intervention as unplanned placement of a nephrostomy tube or ureteral
      stent, balloon dilation or redo pyeloplasty. RESULTS: In the laparoscopic studies
      171 cases (49%) were evaluated by preoperative and 137 (40%) by postoperative
      diuretic renography. Of patients undergoing postoperative diuretic renography 10
      (7%) underwent reoperative intervention, including redo pyeloplasty (6, 4%),
      nephrostomy (3, 2%) and balloon dilation (1, 1%). In the open pyeloplasty studies
      performed elsewhere 165 cases (34%) were evaluated by preoperative and 230 (47%)
      by postoperative diuretic renography. Of patients undergoing postoperative
      diuretic renography redo pyeloplasty was required in 3 (1%). Of 224 cases managed
      by open pyeloplasty at our institution 215 (96%) had preoperative and
      postoperative diuretic renography data available. Of these patients 7 (3%)
      underwent reoperative intervention, including redo pyeloplasty (4, 2%), ureteral
      stent (2, 1%) and nephrostomy (1, 0.4%). CONCLUSIONS: Most publications do not
      confirm preoperative obstruction or, following laparoscopic or open pyeloplasty,
      postoperative success via diuretic renography. While not statistically
      significant, in the minority of studies with postoperative diuretic renography
      results the reoperative intervention rate and redo pyeloplasty rate following
      laparoscopy are approximately double those of open pyeloplasty.

PMID- 19765756
TI  - Multidrug resistance in a urothelial cancer cell line after 1-hour mitomycin C
      exposure.
AB  - PURPOSE: A factor pertinent to the design of cancer chemotherapy is multidrug
      resistance. Research in this area conventionally involves in vitro models using
      resistant cell lines generated by continuous low dose drug exposure for many
      months, unlike the exposure experienced by residual superficial bladder cancer
      cells during chemotherapy adjuvant to resection. Recently we noted a measure of
      multidrug resistance induced by 3 short exposures to mitomycin C during 10 weeks.
      We currently report detectable functional resistance after a single 1-hour
      insult. MATERIALS AND METHODS: RT112 bladder cancer cells (Catalog No. ACC 418,
      Deutsche Sammlung von Mikroorganismen und Zellkulturen, Braunschweig, Germany)
      were exposed to a range of mitomycin C concentrations for 1 hour. Cells regrew in
      3 of 24 cultures at 15.6, 3.91 and 0.98 mg/ml exposure. These cells were
      subjected to 3 functional tests of cross resistance to epirubicin, including MTT
      cytotoxicity assay, quantitative accumulation by flow cytometry and nuclear
      uptake or exclusion by live cell fluorescence microscopy. RESULTS: MTT assay and
      flow cytometry revealed clear indications of resistance. Intracellular
      distribution, in which nuclear exclusion indicates resistance, was distinctively
      resistant in 1 subline and another 2 were equivocal. CONCLUSIONS: Results
      indicate that some multidrug resistance potential exists even in a cloned cell
      line that is capable of surviving 1 short drug exposure and expanding after that
      insult. The exposures used are consistent with those probably experienced by many
      superficial transitional cell carcinoma cells during an intravesical chemotherapy
      application. The result gives added weight to considering multidrug resistance
      induction in dose scheduling or drug combinations for topical chemotherapy.

PMID- 19765757
TI  - Restoring erectile function by antioxidant therapy in diabetic rats.
AB  - PURPOSE: Diabetes mediates an increase in reactive oxygen species that can lead
      to impaired endothelial function, decreased smooth muscle in the diabetic corpus
      cavernosum and increased apoptosis. We hypothesized that antioxidant therapy may
      restore erectile function by inhibiting apoptosis in diabetic rat crura.
      MATERIALS AND METHODS: A total of 40 male Sprague-Dawley rats were randomized to
      5 groups of 8 each, including healthy controls, rats with diabetes, and rats with
      diabetes with the antioxidant tempol (4-hydroxytetramethyl-piperidine-1-oxyl)
      (Sigma-Aldrich), with insulin, and with tempol and insulin. Intracavernous
      pressure was measured for functional analysis. Smooth muscle and collagen fiber
      levels in the rat penile corpus cavernosum were assessed by hematoxylin and
      eosin, and Masson's trichrome staining. Endothelial cells were assessed by CD31
      staining. Reactive oxygen species related genes were analyzed by cDNA microarray.
      We confirmed mRNA and protein expression profiles for these genes in diabetic and
      treated rats using real-time reverse transcriptase-polymerase chain reaction and
      immunohistochemistry. TUNEL assay was done to analyze apoptosis status. RESULTS:
      Intracavernous pressure in diabetic rats was significantly decreased vs controls.
      After treatment with tempol or insulin alone intracavernous pressure was
      significantly increased compared to that in untreated diabetic rats. In the
      diabetic group mean smooth muscle area significantly decreased but was restored
      after combined tempol and insulin. Endothelial cell area in diabetic rats
      significantly decreased and was not restored by any treatments. However,
      apoptosis was restored to normal by combined insulin and tempol. Of 84 reactive
      oxidative stress and antioxidant genes 32 were identified specific to diabetic
      rats compared to healthy controls. UCP3 expression was significantly increased in
      diabetic rats and normal levels were restored by all treatments. CONCLUSIONS: To
      our knowledge this is the first report that tempol and insulin can restore
      erectile function in diabetic rats by inhibiting apoptosis.

PMID- 19765758
TI  - Lymphatic sparing microscopic retroperitoneal varicocelectomy: a preliminary
      experience.
AB  - PURPOSE: One of the most common approaches to varicocele in adolescents is the
      Palomo technique. We report the experience of a single surgeon using a
      modification in which an operating microscope was brought into the field so that
      lymphatics were identified and preserved. By sparing lymphatics we attempted to
      reduce the hydrocele rate to levels achieved with microscopic inguinal and
      subinguinal surgery. MATERIALS AND METHODS: A total of 20 boys with grade III
      varicocele underwent retroperitoneal gonadal vessel ligation with microscope
      assisted sparing of lymphatics between November 2004 and June 2007. Mean patient
      age was 15 years and mean followup was 11.2 months (range 1 to 29). RESULTS:
      Microscopic retroperitoneal varicocelectomy was performed in all patients with
      sparing of lymphatics under high power microscope. Clinical examination was
      performed at 1 week, 3, 6 and 12 months, and then annually to assess for
      recurrence and hydrocele. All boys who were followed had no hydrocele or
      recurrence. CONCLUSIONS: The microscope has had a large role in inguinal and
      subinguinal approaches. However, this technique takes up to 2 hours and
      testicular atrophy has been reported. There were no complications and operative
      time was shorter. Our technique, which uses magnification in the retroperitoneum,
      has not been described previously. It combines the simplicity of the original
      Palomo technique with a short period of microscopic dissection for identification
      and sparing of the lymphatics. This modification results in high success rates
      and fewer postoperative hydroceles.

PMID- 19765759
TI  - Editorial comment.

PMID- 19765760
TI  - Polyorchidism: a meta-analysis.
AB  - PURPOSE: Polyorchidism is an uncommon congenital anomaly. We systematically
      analyzed the literature due to the contradictory data regarding this condition.
      MATERIALS AND METHODS: We conducted a database search and evaluated relevant
      articles for the appearance, comorbidities and complications of supernumerary
      testes. Only cases of polyorchidism confirmed by histological examination were
      included in the study. RESULTS: We found 140 cases of polyorchidism. Triorchidism
      was the most common type, and 6 cases of 4 testes (4.3%) were reported. Most
      supernumerary testes (64%, chi-square p <0.001) were drained by a vas deferens.
      Median patient age at detection was 17 years. Left side demonstrated predominance
      (64.5%, chi-square p <0.001). Most cases were found during surgery for other
      symptoms including inguinal hernia, undescended testicle, testicular torsion and
      scrotal pain. Only 16% of patients complained of an accessory mass without any
      symptoms. Neoplasms were found in 9 cases (6.4%), of which 8 were malignant and 1
      was benign. Data available for 7 malignomas (88%) revealed that all were in
      cryptorchid supernumerary testes. CONCLUSIONS: Polyorchidism is rare and is
      generally found during evaluation for other conditions such as inguinal hernia,
      undescended testis and testicular torsion. Cryptorchidism appears to be the most
      important risk factor for malignancy in patients with supernumerary testes. Thus,
      patients with nonscrotal supernumerary testes require appropriate counseling. The
      supernumerary testis is frequently drained by a vas deferens, implying a probable
      reproductive function. Decision for surgery, biopsy or orchiectomy should be
      based on concomitant symptoms, cryptorchidism or suspected malignancy. We provide
      a guideline for management based on a functional classification of polyorchidism.

PMID- 19765761
TI  - Editorial comment.

PMID- 19765762
TI  - Editorial comment.

PMID- 19765763
TI  - Bladder function after total urogenital mobilization for persistent cloaca.
AB  - PURPOSE: Total urogenital mobilization has achieved widespread use because it
      avoids surgical complications of vaginal reconstruction. We used urodynamic
      studies to assess bladder function and urological outcomes after definitive
      repair by total urogenital mobilization. MATERIALS AND METHODS: We identified 27
      girls diagnosed with persistent cloaca between 1991 and 2008. We retrospectively
      reviewed the records of 11 patients (median age 14 months) who underwent
      reconstruction of the cloaca by total urogenital mobilization. Urinary continence
      was assessed in 7 patients older than 4 years. Urodynamic studies were performed
      postoperatively in 7 patients. Median followup was 72 months. RESULTS: Rate of
      surgical complications was 9%. Urinary continence was achieved in 6 patients
      (86%), while 1 patient (14%) remained incontinent. Of the continent patients 3
      (43%) voided spontaneously and 3 (43%) required clean intermittent
      catheterization. Urodynamic studies showed detrusor underactivity or acontractile
      detrusor in all patients during the voiding phase. Bladder compliance was normal
      in 6 patients (86%) and poor in 1 (14%). Detrusor overactivity was seen in 5
      patients (71%) but resolved on followup in 2 (40%). Rate of continence was higher
      in the absence of detrusor overactivity (1 of 1 patient vs 2 of 3 with detrusor
      overactivity). CONCLUSIONS: Most patients with persistent cloaca can achieve
      urinary continence after total urogenital mobilization. Two-thirds of patients
      display bladder dysfunction after the procedure. Detrusor overactivity can
      resolve with development of the bladder but persistent detrusor overactivity
      might delay the achievement of mechanisms of urinary continence.

PMID- 19765764
TI  - Editorial comment.

PMID- 19765765
TI  - Mechanosensitive primary bladder afferent activity in rats with and without
      spinal cord transection.
AB  - PURPOSE: Spinal cord injury induces functional and morphological changes in
      bladder afferent pathways. However, direct evidence for changes in the
      excitability of afferent nerve activity primarily originating from the bladder
      has not been clearly demonstrated. Thus, we determined the characteristics of
      peripheral mechanosensitive bladder afferents in the pelvic nerve and possible
      afferent changes in Adelta and C fibers after spinal cord injury. MATERIALS AND
      METHODS: Adult female rats were divided into 2 groups, including spinal cord
      injured and neurologically intact animals. In the spinal cord injury group the
      spinal cord was transected at Th9 at 4 weeks before functional experiments. For
      single unit afferent activity monitoring fine filaments were dissected from the
      L6 dorsal root and bladder afferent fibers were identified. Single unit afferent
      activity was studied during constant filling with saline. RESULTS: Two afferent
      patterns were linked to small phasic increases in intravesical pressure during
      bladder filling, including accelerated and nonaccelerated types. The incidence of
      the accelerated type was significantly higher in the spinal cord injury group
      than in the neurologically intact group regarding Adelta and C fibers. However,
      we found no relationship between conduction velocity and the functional
      properties of bladder mechanosensitive afferent fibers in neurologically intact
      or spinal cord injured rats. CONCLUSIONS: Results indicate that mechanosensitive
      bladder afferent activity has several patterns and is facilitated after spinal
      cord injury, especially in concert with small bladder contractions
      (micromotions). The functional properties of these individual afferent fibers are
      not related in an obvious manner to their conduction velocity and, thus, probably
      the afferent fiber type.

PMID- 19765766
TI  - Restoring barrier function to acid damaged bladder by intravesical chondroitin
      sulfate.
AB  - PURPOSE: Chondroitin sulfate (Stellar Pharmaceuticals, London, Ontario, Canada),
      which is less expensive and more inert than heparinoids, hyaluronan or pentosan
      polysulfate, has been introduced to restore the barrier function lost due to
      epithelial dysfunction in interstitial cystitis cases. To our knowledge
      chondroitin sulfate binding to damaged bladder as a function of the urinary pH
      range, its efficacy in restoring the bladder permeability barrier and the
      capacity of the damaged bladder to bind chondroitin sulfate have not been
      determined previously. MATERIALS AND METHODS: Chondroitin sulfate binding to
      bladder urothelium was investigated quantitatively using chondroitin sulfate
      highly labeled with Texas Red(R) and quantitative fluorescence microscopy in a
      mouse model of urothelial acid damage. The efficacy of restoring barrier function
      was determined using the passage of intravesically instilled (86)Rb, a potassium
      ion mimetic, through the urothelium into the bloodstream in a rat model of
      bladder damage. The binding capacity of acid damaged bladder was determined by
      fluorometry. RESULTS: Chondroitin sulfate bound tightly and exclusively to the
      mouse bladder surface damaged by acid but showed only minimal binding to
      undamaged bladder. There was no systematic variation in pH. The model showed some
      variability in the degree of damage induced. In rats chondroitin sulfate
      instillation restored permeability to (86)Rb to control levels. Binding was
      saturable at a mean +/- SEM 0.67 +/- 0.13 mg/cm(2) of the bladder surface.
      CONCLUSIONS: Chondroitin sulfate binds preferentially to damaged urothelium and
      restores the impermeability barrier. This suggests that the glycosaminoglycan
      layer is a major contributor to bladder urothelial impermeability. As determined
      by binding capacity, the dose applied in humans in Canada (400 mg per
      instillation) is sufficient to achieve maximum efficacy.

PMID- 19765767
TI  - Editorial comment.

PMID- 19765768
TI  - Editorial comment.

PMID- 19765769
TI  - Effect of potassium citrate therapy on the risk of renal stone formation during
      spaceflight.
AB  - PURPOSE: Exposure to microgravity affects human physiology and results in changes
      in urinary chemical composition during and after spaceflight, favoring an
      increased risk of renal stones. We assessed the efficacy of potassium citrate to
      decrease the stone risk during and after spaceflight. MATERIALS AND METHODS: The
      study was done in 30 long duration spaceflight crew members to the space stations
      Mir and International Space Station. Before, during and after spaceflight 24-hour
      urine samples were collected to assess the renal stone risk. Potassium citrate
      (20 mEq) was ingested daily by International Space Station crew members in a
      double-blind, placebo controlled study. Mir crew members performed the identical
      protocol but did not ingest medication. RESULTS: Potassium citrate treated crew
      members had decreased urinary calcium excretion and maintained the calcium
      oxalate supersaturation risk at preflight levels compared to that in controls.
      Increased urinary pH in the treatment group decreased the risk of uric acid
      stones. CONCLUSIONS: Results from this investigation suggest that supplementation
      with potassium citrate may decrease the risk of renal stone formation during and
      immediately after spaceflight.

PMID- 19765770
TI  - Estrogen effects on fetal penile and urethral development in organotypic mouse
      genital tubercle culture.
AB  - PURPOSE: We developed an organotypic genital tubercle culture system in vitro and
      used it to investigate the direct effects of the hyperestrogenic state on fetal
      mouse penile and urethral development. MATERIALS AND METHODS: Genital tubercles
      were dissected from embryonic day 14.5 C57B/L6 male mouse fetuses and cultured
      using an air-liquid interface on a microporous membrane support soaked in
      synthetic medium. Cultures were separated into 4 groups. Groups 1 to 3 were
      supplied with 10 nM dihydrotestosterone, estradiol and 10 nM dihydrotestosterone
      plus estradiol, respectively. Group 4 was cultured in hormone-free medium. After
      36 to 72-hour culture morphological, histological, proliferation, apoptosis,
      androgen signaling and activating transcription factor 3 analyses were done.
      RESULTS: The physiological concentration of 10 nM dihydrotestosterone was
      essential for genital tubercle growth in vitro. Androgen induced growth and
      urethral development were significantly suppressed by high dose estrogen.
      Concurrently we observed increased apoptosis and decreased proliferation in the
      mesenchyma. Androgen signaling was disrupted and activating transcription factor
      3, a factor related to hypospadias genesis, was up-regulated. CONCLUSIONS: High
      dose estrogen suppressed male genital tubercle development in vitro. The
      organotypic genital tubercle culture system in vitro consisting of urethral
      epithelial and mesenchymal cells can recapitulate the hormonal sensitivity of
      fetal penile and urethral development. This method is potentially useful for
      studying the effects of various factors, particularly endocrine disruptors.

PMID- 19765771
TI  - Change of urodynamic patterns in infants with dilating vesicoureteral reflux: 3
      year followup.
AB  - PURPOSE: Reports concerning bladder dysfunction patterns in infants with high
      grade vesicoureteral reflux during the first year of life vs older children with
      reflux are contradictory. To describe the development of bladder function
      characteristics in children with congenital dilating reflux, we evaluated such
      infants urodynamically and followed them regularly for a 3-year period. MATERIALS
      AND METHODS: A total of 89 males and 25 females with grade III to V dilating
      reflux were evaluated 3 times using videocystometry at mean ages of 6, 20 and 40
      months. RESULTS: Characteristics of the urodynamic pattern at 6 months could not
      be differentiated from normal patterns for that age, including low and normal
      bladder capacity, high voiding pressure levels, dyscoordination at voiding (80%)
      and overactivity during filling (60%). However, at 20 months the overall pattern
      was different, including increased bladder capacity and residual volume, normal
      voiding pressure, persistent overactivity during filling and dyscoordination at
      voiding. Bladder dysfunction was seen in 48 children (42%) at 20 months, of whom
      34 primarily had high bladder capacity with incomplete emptying (dilated bladder
      dysfunction) and 14 had overactive bladder. Predictors for development of dilated
      bladder dysfunction at followup were high residual urine at 6-month examination
      and recurrent urinary tract infections. Recurrent infections were significantly
      correlated to high residual urine at all investigations and to detrusor
      overactivity at the 20-month examination. CONCLUSIONS: Urodynamic patterns
      changed between the first and second year of life in patients with dilating
      reflux, from an immature pattern with high pressure levels to high capacity
      bladder with incomplete voiding. Therefore, bladder dysfunction, which was seen
      in 42% of patients, was only possible to diagnose after the first year of life
      and was mainly seen as high capacity bladder with incomplete voiding.

PMID- 19765773
TI  - Insulin resistance and inflammation may have an additional role in the link
      between cystatin C and cardiovascular disease in type 2 diabetes mellitus
      patients.
AB  - Recent studies suggest that serum cystatin C level is not only a sensitive marker
      for renal dysfunction but also a predictive marker for cardiovascular disease
      (CVD). However, the mechanism of this connection is not fully understood. We
      aimed to determine whether insulin resistance or various biomarkers of
      cardiovascular risk have a role in the link between cystatin C and CVD in type 2
      diabetes mellitus patients. Anthropometric measurements and biochemical studies
      including inflammatory biomarkers were performed in 478 patients with type 2
      diabetes mellitus. The degree of insulin resistance was assessed by homeostasis
      model assessment (HOMA-IR) and indicators of metabolic syndrome. Estimated
      glomerular filtration rate (eGFR) was derived from the Modification of Diet in
      Renal Disease study equation. After adjusting for age, sex, body mass index, and
      eGFR, the cystatin C level increased significantly in proportion to the number of
      metabolic syndrome components present (1.08 +/- 0.06, 1.19 +/- 0.04, 1.20 +/-
      0.04, 1.23 +/- 0.04, and 1.37 +/- 0.06 mg/L; P < .0001); and HOMA-IR increased
      significantly in proportion to cystatin C quartiles (1.16 +/- 0.15, 1.40 +/-
      0.13, 1.49 +/- 0.13, and 2.00 +/- 0.17; P < .0001) (means +/- SE). Albumin
      creatinine ratio, fibrinogen, uric acid, homocysteine, high-sensitivity C
      reactive protein, and lipoprotein(a) all showed significant correlations with
      cystatin C that were generally higher than those with eGFR. Cystatin C level was
      independently associated with HOMA-IR (beta = 0.0380, P = .0082), albumin
      creatinine ratio (beta = 0.0004, P < .0001), uric acid (beta = 0.0666, P <
      .0001), and homocysteine (beta = 0.0087, P = .0004). In conclusion, cystatin C
      level was significantly associated with insulin resistance and biomarkers
      reflecting inflammation independent of renal function. These components may have
      a role in addition to that of eGFR in explaining the link between cystatin C and
      CVD in type 2 diabetes mellitus patients.

PMID- 19765774
TI  - A metabolic cause of spinal deformity.
AB  - A 38-year-old man presented to our clinic with a 6-year history of chronic low
      back pain. Physical examination showed limited spine mobility; radiographs of the
      spine demonstrated narrowed disk spaces and calcifications. Lumbar spine magnetic
      resonance imaging showed Modic type II signal intensity changes in the bone
      marrow consistent with chronic disk degeneration. The finding of a massively
      elevated excretion of homogentisic acid (HGA) in the patient's urine confirmed
      the suspicion that the complaints were due to underlying alkaptonuria.
      Alkaptonuria (ochronosis) is an uncommon cause of backache and results from
      mutations in homogentisate 1,2-dioxygenase, an enzyme involved in tyrosine
      catabolism. Homogentisic acid accumulates in the plasma of the affected
      individuals, and HGA polymers deposit in connective tissues where they cause
      cartilage degeneration. So far, there is no proven treatment; but preclinical and
      phase I data with nitisinone, an inhibitor of HGA formation, are promising.
      Currently, the effects of nitisinone on joint mobility are being evaluated in a
      randomized trial. Clinicians involved in the care of musculoskeletal problems
      should be aware of this rare disorder, particularly because the correct diagnosis
      may have therapeutic implications.

PMID- 19765775
TI  - The relationship of visfatin/pre-B-cell colony-enhancing factor/nicotinamide
      phosphoribosyltransferase in adipose tissue with inflammation, insulin
      resistance, and plasma lipids.
AB  - Visfatin/pre-B-cell colony-enhancing factor (PBEF)/nicotinamide
      phosphoribosyltransferase (Nampt) has been proposed as an insulin-mimicking
      adipocytokine predominantly secreted from visceral adipose tissue (VAT) and
      correlated with obesity. However, recent evidence challenged this proposal and
      instead suggested visfatin/PBEF/Nampt as a proinflammatory cytokine. The study
      aimed to examine whether visfatin/PBEF/Nampt was predominantly expressed in VAT
      and was correlated with obesity. The relationship of visfatin/PBEF/Nampt gene
      expression in adipose tissues with proinflammatory gene expression and metabolic
      phenotypes was also examined. The relative messenger RNA (mRNA) levels of
      visfatin/PBEF/Nampt, macrophage-specific marker CD68, and proinflammatory genes
      were measured in paired abdominal VAT and subcutaneous adipose tissues (SAT) and
      from 53 nondiabetic adults using quantitative real-time polymerase chain
      reaction. Fasting glucose, insulin, triglyceride, cholesterol, and uric acid
      levels were measured; and systemic insulin sensitivity was quantified with
      modified insulin suppression tests. There was no difference in
      visfatin/PBEF/Nampt mRNA levels between VAT and SAT, and neither was associated
      with measures of obesity. Visfatin/PBEF/Nampt mRNA levels were strongly
      correlated with proinflammatory gene expression including CD68 and tumor necrosis
      factor-alpha gene in both VAT and SAT. The VAT and SAT visfatin/PBEF/Nampt mRNA
      expressions were positively correlated with steady-state plasma glucose
      concentrations measured with modified insulin suppression tests, a direct
      measurement of systemic insulin resistance (r = 0.42, P = .03 and r = 0.44, P =
      .03, respectively). The VAT visfatin/PBEF/Nampt mRNA expression was also
      positively correlated with fasting triglyceride (r = 0.42, P = .002) and total
      cholesterol levels (r = 0.37, P = .009). Visfatin/PBEF/Nampt is not predominantly
      secreted from VAT and is not correlated with obesity. Our findings suggest that
      visfatin/PBEF/Nampt is a proinflammatory marker of adipose tissue associated with
      systemic insulin resistance and hyperlipidemia.

PMID- 19765776
TI  - Superoxide production by mitochondria of insulin-sensitive tissues: mechanistic
      differences and effect of early diabetes.
AB  - Obesity and mild hyperglycemia are characteristic of early or "prediabetes." The
      associated increase in fatty acid flux is posited to enhance substrate delivery
      to mitochondria, leading to enhanced superoxide production that results in
      mitochondrial dysfunction and progressive worsening of the hyperglycemic state.
      We quantified superoxide production by gastrocnemius muscle, heart, and liver
      mitochondria in a rodent model that mimics the pathophysiology of prediabetes by
      administering low-dose streptozotocin to rats fed high fat (HF). Superoxide was
      rigorously determined indirectly as H(2)O(2) largely released from the matrix and
      by electron paramagnetic resonance spectroscopy that directly detects superoxide
      released externally. Both HF and low-dose streptozotocin mildly increased
      glycemia (P < .05 by 2-way analysis of variance). Matrix and external superoxide
      production by gastrocnemius mitochondria respiring on the complex II substrate
      succinate and matrix superoxide production by liver mitochondria respiring on the
      complex I substrates glutamate plus malate were significantly reduced by HF
      feeding but not affected by mild hyperglycemia. Superoxide production was not
      significantly altered by either treatment in heart mitochondria fueled by either
      complex I or II substrates. The functional status of the mitochondria was assayed
      as simultaneous respiration and membrane potential that were not affected by HF
      or mild hyperglycemia. Comparison of substrate and inhibitor effects on
      superoxide release implied marked differences in the redox mechanisms regulating
      mitochondrial superoxide production from liver mitochondria compared with muscle
      and heart. In summary, superoxide production from mitochondria of different
      insulin-sensitive tissues differs mechanistically. However, in any case, excess
      superoxide production as an intrinsic property of mitochondria of insulin
      sensitive tissues does not result from conditions mimicking the pathophysiology
      of pre- or early diabetes.

PMID- 19765777
TI  - Serum aminotransferase changes with significant weight loss: sex and age effects.
AB  - In obese subjects, the liver may be differentially affected by significant weight
      loss depending on as yet unknown factors. We explored clinical factors associated
      with serum alanine aminotransferase (ALT) changes during significant weight loss
      in a residential weight loss program. Clinical data from 362 adults who received
      a comprehensive weight loss intervention (ie, diets, physical fitness, and
      behavioral modification) in the program were analyzed. Serum ALT was used as a
      surrogate marker of liver injury. The ALT changes during the program were
      calculated to create study outcome categories (improvement, no change, or
      deterioration of ALT during significant weight loss). Variables of demography,
      lifestyle, and comorbidities at baseline, and total/rate of weight change during
      the program were explored for associations with the ALT change categories using
      multiple logistic regression models. Variation by sex was apparent among
      predictors of ALT deterioration; men with rapid weight loss and women with higher
      initial body mass index were more likely to experience ALT deterioration, whereas
      men with prior alcohol consumption were less likely to experience ALT
      deterioration even after adjusting for baseline ALT (Ps < .03). Variation by age
      was apparent among predictors of ALT improvement; younger patients with current
      smoking and older patients with rapid weight loss, diabetes or impaired fasting
      glucose, or sleep apnea or who followed a reduced-carbohydrate diet were less
      likely to experience ALT improvement (Ps < .05). A number of clinical factors
      influence ALT changes during weight loss in sex- and age-specific manners. The
      patterns that we detected may have pathophysiologic significance beyond the
      practical implications of our findings in clinical practice related to underlying
      changes in fat metabolism.

PMID- 19765778
TI  - Sex hormone-binding globulin and lipid profile in pubertal children.
AB  - Men and women have different lipid profiles throughout life, related to changes
      in sex hormones; and this has been associated with sex-related differences in the
      prevalence of coronary heart disease. The influence of sex hormone changes during
      puberty on the lipid profile has been reported, but levels of sex hormone-binding
      globulin (SHBG) (the specific plasma binding protein of sex hormones) have not
      been evaluated even though its regulatory role might be crucial. The aim of this
      study was to analyze the relationship between sex hormones and SHBG and changes
      in plasma lipid levels during puberty. Our population-based sample included 370
      healthy schoolchildren (175 male and 195 female), ranging from 12 to 15 years
      old. High-density lipoprotein cholesterol (HDL-C) levels were significantly lower
      in 15-year-olds than in younger boys, and apolipoprotein (apo) A-I levels steeply
      decreased across the studied age groups. Parallel to these changes, testosterone
      levels increased whereas SHBG decreased as age increases in boys. In girls, no
      significant differences were observed in these variables among the age groups.
      Testosterone and SHBG were highly correlated with anthropometric variables. Sex
      hormone-binding globulin was negatively associated with triglycerides (TG) in
      both sexes, remaining statistically significant after further adjustment for age
      and body mass index (BMI) in girls. Sex hormone-binding globulin was the only
      predictive variable for HDL-C and TG in multiple linear regression analysis,
      after adjustment by BMI, in both sexes, accounting for 10% of the variance of HDL
      C in boys and for around 5% of the variance of TG in both sexes. In boys,
      testosterone and SHBG remained significantly correlated to apo A-I levels, even
      after adjusting for age and BMI, and were the most important predictive variables
      for apo A-I in multiple linear regression analysis. In conclusion, SHBG levels
      are related to a decrease in HDL-C and apo A-I levels during puberty in boys and
      to a decrease in TG levels during puberty in both sexes.

PMID- 19765779
TI  - Circulating adiponectin concentrations were related to free thyroxine levels in
      thyroid cancer patients after thyroid hormone withdrawal.
AB  - Because it is unclear whether adipose-derived hormones are related to thyroid
      hormone metabolism, this study evaluated the relationship between adiponectin
      concentrations and changes in the thyroid hormones in athyreotic patients after
      thyroid hormone withdrawal. Twenty-eight athyreotic thyroid cancer patients (4
      male and 24 female; mean age, 52.2 +/- 11.3 years) were analyzed on the final day
      of levothyroxine treatment and 1 day before serum thyroglobulin and radioiodine
      scanning examinations after an average of 4 weeks of thyroid hormone withdrawal.
      Evaluations included analysis of thyroid function test, serum adiponectin, body
      composition by bioimpedance analysis, and insulin sensitivity index as determined
      by the homeostasis model assessment of insulin resistance (HOMA-IR).
      Discontinuation of thyroid hormone treatment resulted in a significant change in
      thyroid-stimulating hormone (82.1 +/- 9.8 vs 1.0 +/- 0.4 mL/L, P < .05), free
      thyroxine (FT4) (5.7 +/- 0.4 vs 18.7 +/- 2.3 pmol/L, P < .05), and free
      triiodothyronine levels (1.8 +/- 0.2 vs 3.4 +/- 0.2 pmol/L, P < .05) as compared
      with the prewithdrawal values, whereas circulating adiponectin levels (5.7 +/-
      0.6 vs 5.4 +/- 0.6 mg/L), body fat mass (20.3 +/- 1.2 vs 19.4 +/- 1.2 kg), and
      insulin sensitivity index (1.8 +/- 0.2 vs 2.2 +/- 0.3) remained unaltered. A
      positive correlation between adiponectin and FT4 (r = 0.61, P < .01) independent
      of age, sex, fat body mass, HOMA-IR, and other potential covariates known to
      affect thyroid hormone metabolism, such as renal and liver functions, was
      observed after thyroid hormone withdrawal. In addition, baseline circulating
      adiponectin levels were correlated with a diminished postwithdrawal reduction of
      FT4 concentrations after adjusting for baseline FT4 levels and changes in body
      mass index, fat body mass, and HOMA-IR (r = 0.71, P < .01). In conclusion,
      adiponectin concentrations were associated with FT4 levels in the athyreotic
      patients after thyroid hormone withdrawal. The relevant roles of adiponectin in
      the regulation of thyroid hormone metabolism require further investigation.

PMID- 19765780
TI  - Failure of d-psicose absorbed in the small intestine to metabolize into energy
      and its low large intestinal fermentability in humans.
AB  - Experiments with rats have produced data on the metabolism and energy value of d
      psicose; however, no such data have been obtained in humans. The authors assessed
      the availability of d-psicose absorbed in the small intestine by measuring
      carbohydrate energy expenditure (CEE) by indirect calorimetry. They measured the
      urinary excretion rate by quantifying d-psicose in urine for 48 hours. To examine
      d-psicose fermentation in the large intestine, the authors measured breath
      hydrogen gas and fermentability using 35 strains of intestinal bacteria. Six
      healthy subjects participated in the CEE test, and 14 participated in breath
      hydrogen gas and urine tests. d-Psicose fermentation subsequent to an 8-week
      adaptation period was also assessed by measuring hydrogen gas in 8 subjects. d
      Psicose absorbed in the small intestine was not metabolized into energy, unlike
      glucose, because CEE did not increase within 3 hours of d-psicose ingestion (0.35
      g/kg body weight [BW]). The accumulated d-psicose urinary excretion rates were
      around 70% for 0.34, 0.17, and 0.08 g/kg BW of ingested d-psicose. Low d-psicose
      fermentability was observed in intestinal bacteria and breath hydrogen gas tests,
      in which fructooligosaccharide (0.34, 0.17, and 0.08 g/kg BW) was used as a
      positive control because its available energy is known to be 8.4 kJ/g. Based on
      the results of the plot of breath hydrogen concentration vs calories ingested,
      the energy value of d-psicose was expected to be less than 1.6 kJ/g. Incremental
      d-psicose fermentability subsequent to an adaptation period was not observed.

PMID- 19765781
TI  - Contribution of skeletal muscle mass on sex differences in 2-hour plasma glucose
      levels after oral glucose load in Thai subjects with normal glucose tolerance.
AB  - Women have higher 2-hour plasma glucose levels after oral glucose challenge than
      men. The smaller skeletal muscle mass in women may contribute to the higher
      postload glucose levels. The objective of this study was to test the hypothesis
      that the different amount of skeletal muscle mass between men and women
      contributed to sex difference in postload plasma glucose levels in subjects with
      normal glucose tolerance. Forty-seven Thai subjects with normal glucose
      tolerance, 23 women and 24 age- and body mass index-matched men, were studied.
      Body fat, abdominal fat, and appendages lean mass were measured by dual-energy x
      ray absorptiometry. Skeletal muscle insulin sensitivity was determined by
      euglycemic-hyperinsulinemic clamp. First-phase insulin secretion and hepatic
      insulin sensitivity were determined from oral glucose tolerance data. beta-Cell
      function was estimated from the homeostasis model assessment of %B by the
      homeostasis model assessment 2 model. Correlation and linear regression analysis
      were performed to identify factors contributing to variances of postload 2-hour
      plasma glucose levels. This study showed that women had significantly higher 2
      hour plasma glucose levels and smaller skeletal muscle mass than men. Measures of
      insulin secretion and insulin sensitivity were not different between men and
      women. Male sex (r = -0.360, P = .013) and appendages lean mass (r = -0.411, P =
      .004) were negatively correlated with 2-hour plasma glucose, whereas log 2-hour
      insulin (r = 0.571, P < .0001), total body fat (r = 0.348, P = .016), and log
      abdominal fat (r = 0.298, P = .042) were positively correlated with 2-hour plasma
      glucose. The correlation of 2-hour plasma glucose and sex disappeared after
      adjustment for appendages lean mass. By multivariate linear regression analysis,
      log 2-hour insulin (beta = 18.9, P < .0001), log 30-minute insulin (beta = -36.3,
      P = .001), appendages lean mass (beta = -1.0 x 10(-3), P = .018), and hepatic
      insulin sensitivity index (beta = -17.3, P = .041) explained 54.2% of the
      variance of 2-hour plasma glucose. In conclusion, the higher postload 2-hour
      plasma glucose levels in women was not sex specific but was in part a result of
      the smaller skeletal muscle mass. The early insulin secretion, hepatic insulin
      sensitivity, and skeletal muscle mass were the significant factors negatively
      predicting 2-hour postload plasma glucose levels in Thai subjects with normal
      glucose tolerance.

PMID- 19765772
TI  - [The evolution of quality care indicators of patients with type 2 diabetes in the
      Spanish primary care (1996-2007). The RedGEDAPS quality of care program].

PMID- 19765782
TI  - Effects of exercise on insulin sensitivity, inflammatory cytokines, and serum
      tartrate-resistant acid phosphatase 5a in obese Chinese male adolescents.
AB  - The benefits of exercise on glucose metabolism, inflammation, and serum tartrate
      resistant acid phosphatase 5a (TRACP 5a) protein levels in Chinese male
      adolescents have not been extensively analyzed. Therefore, we examined the
      effects of a 12-week exercise program on weight, adiposity, insulin sensitivity
      (IS), and inflammatory marker expression, including the novel macrophage marker
      TRACP 5a, in obese Chinese male adolescents. A total of 106 male adolescents were
      recruited from the Army Academy in Taiwan and classified as lean (body mass index
      [BMI], 20.9 +/- 0.2 kg/m(2)) or obese (BMI, 27.7 +/- 0.2 kg/m(2)). Body
      composition, IS, and inflammatory markers were measured in both groups at
      baseline and in the obese group after completion of a 12-week exercise program.
      Body weight, BMI, waist circumference, body fat mass and percentage, homeostasis
      model assessment for insulin resistance, fasting plasma glucose, fasting serum
      insulin, 2-hour postchallenge plasma glucose concentration, interleukin-6, C
      reactive protein, and serum TRACP 5a were significantly higher in the obese group
      as compared with the lean group. In addition, serum TRACP 5a was positively
      correlated with body mass and fat indices. After completion of the exercise
      program, significant reductions in all anthropometric, metabolic, and
      inflammatory indicators, with the exception of serum TRACP 5a were observed.
      Although the obese participants remained obese, exercise training significantly
      improved IS and reduced interleukin-6 and C-reactive protein. Tartrate-resistant
      acid phosphatase 5a remained unaffected by exercise training, consistent with our
      hypothesis that it is associated with increased adipose tissue in obese
      individuals.

PMID- 19765783
TI  - Acute exposure to rosiglitazone does not affect glucose transport in intact human
      skeletal muscle.
AB  - Thiazolidinediones (TZDs) such as rosiglitazone are widely used as antidiabetic
      drugs. Animal studies suggest that TZDs may have direct metabolic actions in
      skeletal muscle. Here, we examined if acute exposure to rosiglitazone stimulates
      glucose transport rate and affects proximal insulin signaling in isolated
      skeletal muscle strips from nondiabetic men. Open muscle biopsies were obtained
      from musculus vastus lateralis from 15 nondiabetic men (50 +/- 3 years old, 26.9
      +/- 1.1 kg/m(2)). Skeletal muscle strips were isolated and exposed to
      rosiglitazone (1 or 10 micromol/L), 5-aminoimidazole-4-carboxamide 1-beta-D
      ribonucleoside (1 mmol/L), insulin (120 nmol/L), or a combination of insulin (120
      nmol/L) and rosiglitazone (10 micromol/L) in vitro for 1 hour. Glucose transport
      was analyzed by accumulation of intracellular 3-O-methyl [(3)H] glucose;
      phosphorylation of Akt-Ser(473) and Akt-Thr(308) and phosphorylation of acetyl
      coenzyme A carboxylase beta were determined using phosphospecific antibodies. 5
      Aminoimidazole-4-carboxamide 1-beta-d-ribonucleoside and insulin increased
      glucose transport rate 1.5-fold (P < .05) and 1.7-fold (P < .01) in isolated
      muscle strips, respectively. Exposure to rosiglitazone transiently increased
      phosphorylation of acetyl coenzyme A carboxylase beta, with a maximum effect at
      15 minutes and return to baseline at 60 minutes. However, rosiglitazone did not
      affect basal or insulin-stimulated glucose transport rate, or phosphorylation of
      Akt-Ser(473) or Akt-Thr(308) in isolated muscle strips. In conclusion, acute
      exposure to rosiglitazone does not affect glucose transport in human skeletal
      muscle.

PMID- 19765784
TI  - Acute altitude-induced hypoxia suppresses plasma glucose and leptin in healthy
      humans.
AB  - To examine the effects of acute altitude-induced hypoxia on the hormonal and
      metabolic response to ingested glucose, 8 young, healthy subjects (5 men and 3
      women; age, 26 +/- 2 years; body mass index, 23.1 +/- 1.0 kg/m(2)) performed 2
      randomized trials in a hypobaric chamber where a 75-g glucose solution was
      ingested under simulated altitude (ALT, 4300 m) or ambient (AMB, 362 m)
      conditions. Plasma glucose, insulin, C-peptide, epinephrine, leptin, and lactate
      concentrations were measured at baseline and 30, 60, 90, and 120 minutes after
      glucose ingestion during both trials. Compared with AMB, the plasma glucose
      response to glucose ingestion was reduced during the ALT trial (P = .04). There
      were no differences in the insulin and C-peptide responses between trials or in
      insulin sensitivity based on the homeostasis model assessment of insulin
      resistance. Epinephrine and lactate were both elevated during the ALT trial (P <
      .05), whereas the plasma leptin response was reduced compared with AMB (P < .05).
      The data suggest that the plasma glucose response is suppressed at ALT, but this
      is not due to insulin per se because insulin and C-peptide levels were similar
      for both trials. Elevated plasma epinephrine and lactate during ALT are
      indicative of increased glycogenolysis, which may have masked the magnitude of
      the reduced glucose response. We conclude that, during acute altitude exposure,
      there is a rapid metabolic response that is accompanied by a shift in the
      hormonal milieu that appears to favor increased glucose utilization.

PMID- 19765785
TI  - Characterization of a highly stable trypsin-like proteinase inhibitor from the
      seeds of Opuntia streptacantha (O. streptacantha Lemaire).
AB  - A trypsin inhibitor from Opuntia streptacantha Lemaire (Prickly pear) seeds was
      purified and characterized. Of several proteases tested, this inhibitor showed
      specificity to trypsin-like enzymes. The major inhibitor present in these seeds
      showed distinctive characteristics, most notably a low molecular weight of 4.19
      kDa, as determined by MALDI TOF, and an unusually high thermal stability,
      retaining most of the activity after heating the sample 1h to 120 degrees C with
      a pressure of 1 kg/cm(2). Its complete amino acid sequence was obtained through
      mass spectrometry, this establishing presence a blocked N-terminal region. When
      comparing its sequence in the MEROPS database for peptidases and peptidase
      inhibitors, it showed 34.48% identity with a serine-proteinase inhibitor from the
      I15 family.

PMID- 19765786
TI  - Methyl angolensate changes in Khaya ivorensis after fungal infection.
AB  - Khaya ivorensis with and without symptoms of stem and branch cankers, caused by
      Botryosphaeria rhodina were examined in order to determine whether the secondary
      metabolites in this plant were associated with a chemical defense response. This
      study provides evidence that the limonoid methyl angolensate (MA) is present at
      higher concentrations in K. ivorensis with symptoms of stem cankers rather than
      in the plants without symptoms. A rapid, sensitive and selective HPLC-ESI-MS/MS
      method (using selected reaction monitoring--SRM--mode) was developed for
      quantification of MA in all aerials parts of such plants, with a good linearity
      over a range of 0.1-20.0 g/kg, with r(2)>0.996+/-6.1%. The limits of detection
      (LOD) and quantification (LOQ) were less than 0.03 g/kg and 0.08 g/kg,
      respectively. Relative Standard Deviations (RSDs) ranged from 1.7% to 19.2% for
      all matrices. While the MA concentration did not change in the stem bark, its
      amounts increased nearly fourfold in stems and by 20% in leaves, when plants with
      symptoms were compared with those without symptoms. These data suggest that MA
      plays a role in plant-pathogen interactions, probably as a phytoanticipin.

PMID- 19765787
TI  - Diversity of Campylobacter jejuni and Campylobacter coli genotypes from human and
      animal sources from Rio de Janeiro, Brazil.
AB  - To compare the genotypes of Campylobacter jejuni and Campylobacter coli isolates
      of human and animal origin collected in Rio de Janeiro City, 30 C. jejuni and 35
      C. coli isolates from animal sources (n=45) and human patients with
      gastroenteritis (n=20) were genotyped by PCR-based techniques, namely random
      amplified polymorphic DNA (RAPD-PCR) and enterobacterial repetitive intergenic
      consensus sequence (ERIC-PCR). RAPD-PCR identified 50 types and ERIC-PCR
      identified 22 genotypes, among the 65 Campylobacter isolates. Both PCR methods
      discriminated the C. jejuni and C. coli groups of isolates. Combining the results
      of both methods, no single genotype was shared between isolates from human and
      animal sources. Two groups of two C. coli isolates each with identical genotypes
      were found among poultry and pig isolates. A high level of genetic diversity
      observed among the Campylobacter isolates suggests lack of overlap between
      isolates from different sources.

PMID- 19765788
TI  - Performance of a prototype malaria rapid diagnostic test versus thick film
      microscopy among HIV-positive subjects in rural Rakai, Uganda.
AB  - In this study, we report the performance of a prototype malaria rapid diagnostic
      test, Malaria F-test (MFT), compared with thick blood films from HIV-positive
      Ugandans undergoing malaria testing. In total, 21/154 samples (13.6%) were
      concordantly positive by both thick film and MFT and 129/154 samples (83.8%) were
      concordantly negative; 1 sample (0.6%) was thick film-positive but MFT-negative
      and 3 samples (1.9%) were thick film-negative but MFT-positive. The sensitivity
      of MFT was 95.5% (95% CI 77.2-99.9%) compared with thick film microscopy and the
      specificity was 97.7% (95% CI 93.5-99.5%). MFT was simple, rapid and effective
      for detection of Plasmodium falciparum among HIV-positive subjects in a rural,
      malaria-endemic African setting.

PMID- 19765789
TI  - Torquetenovirus DNA drives proinflammatory cytokines production and secretion by
      immune cells via toll-like receptor 9.
AB  - Active infection with torquetenovirus (TTV) has been associated with an increased
      severity of diseases in which inflammation plays a particularly important
      pathogenetic role. Here, we report that cloned DNA of a genogroup 4 TTV (ViPiSAL)
      is an activator of proinflammatory cytokine production by murine spleen cells and
      that the effect is mediated via toll-like receptor (TLR)9. The same DNA also
      increased the levels of proinflammatory cytokines induced by two well
      characterized TLR9 stimulants. Finally, in silico analyses of the genomes of
      ViPiSAL and other TTVs revealed marked differences in the representation of CpG
      motifs known to be most effective at activating immune cells via TLR9. These
      findings demonstrate for the first time that at least one TTV isolate has the
      potential to stimulate and co-stimulate inflammatory responses.

PMID- 19765790
TI  - Characterization of human adenovirus serotypes 5, 6, 11, and 35 as anticancer
      agents.
AB  - Human adenovirus type 5 (Ad5) has been the most popular platform for the
      development of oncolytic Ads. Alternative Ad serotypes with low seroprevalence
      might allow for improved anticancer efficacy in Ad5-immune patients. We studied
      the safety and efficacy of rare serotypes Ad6, Ad11 and Ad35. In vitro
      cytotoxicity of the Ads correlated with expression of CAR and CD46 in most but
      not all cell lines. Among CAR-binding viruses, Ad5 was often more active than
      Ad6, among CD46-binding viruses Ad35 was generally more cytotoxic than Ad11 in
      cell culture studies. Ad5, Ad6, and Ad11 demonstrated similar anticancer activity
      in vivo, whereas Ad35 was not efficacious. Hepatotoxicity developed only in Ad5
      injected mice. Predosing with Ad11 and Ad35 did not increase infection of
      hepatocytes with Ad5-based vector demonstrating different interaction of these
      Ads with Kupffer cells. Data obtained in this study suggest developing Ad6 and
      Ad11 as alternative Ads for anticancer treatment.

PMID- 19765791
TI  - Synthesis and characterization of a novel cationic chitosan-based flocculant with
      a high water-solubility for pulp mill wastewater treatment.
AB  - In this work, pulp mill wastewater was treated using a novel copolymer flocculant
      with a high water-solubility, which was synthesized through grafting (2
      methacryloyloxyethyl) trimethyl ammonium chloride (DMC) onto chitosan initiated
      by potassium persulphate. The experimental results demonstrate that the two main
      problems associated with the utilization of chitosan as a flocculant, i.e., low
      molecular weight and low water-solubility, were concurrently sorted out. The
      physicochemical properties of this flocculant were characterized with Fourier
      transform infrared spectroscopy, (1)H nuclear magnetic resonance spectroscopy, X
      ray powder diffraction and field emission scanning electron microscopy. Reaction
      parameters influencing the grafting percentage, such as temperature, reaction
      time, initiator concentration and monomer concentration, were optimized using an
      orthogonal array design matrix. With an increase in grafting percentage, the
      water-solubility of the flocculant was improved, and it became thoroughly soluble
      in water when the grafting percentage reached 236.4% or higher. Its application
      for the treatment of pulp mill wastewater indicates that it had an excellent
      flocculation capacity and that its flocculation efficiency was much better than
      that of polyacrylamide. The optimal conditions for the flocculation treatment of
      pulp mill wastewater were also obtained.

PMID- 19765792
TI  - Concentrations of host-specific and generic fecal markers measured by
      quantitative PCR in raw sewage and fresh animal feces.
AB  - We measured the concentrations of four host-specific (human, dog, cow, and horse
      Bacteroidales), four generic fecal (16S total Bacteroidales and Escherichia coli,
      23S Enterococcus and uidA E. coli,) and two universal bacterial (16S universal
      and rpoB universal) DNA targets by qPCR in raw sewage and pooled fecal samples
      from dogs, cows, horses, and Canada Geese. A spiking protocol using the non-fecal
      bacterium Pseudomonas syringae pph 6 was developed to estimate the recovery of
      DNA from fecal and environmental samples. The measured fecal marker
      concentrations were used to calculate baseline ratios and variability of host
      specific to generic indicators for each host type. The host-specific markers were
      found in high concentrations (8-9 log(10)copies/g dry wt.) in their respective
      hosts' samples, which were equal to or greater than the concentrations of generic
      E. coli and Enterococcus markers, lending support to the use of host-specific and
      generic Bacteroidales as sensitive indicators of fecal pollution. The host
      specific markers formed a consistent percentage of total Bacteroidales in target
      host feces and raw sewage, with human-specific comprising 82%, dog-specific 6%,
      cow-specific 4% and horse-specific 2%. Based on this limited data set, the
      measurement of host-specific indicators by qPCR has several promising
      applications. These applications include determining the percentage of total
      Bacteroidales contributed by a specific host type, using the ratios of host
      specific markers to E. coli or Enterococcus to estimate the contribution of each
      source to these regulated fecal indicator bacteria, and estimating the mass of
      feces from each host type in environmental samples.

PMID- 19765793
TI  - Towards understanding inter-strain attachment variations of Escherichia coli
      during transport in saturated quartz sand.
AB  - Although Escherichia coli is an indicator of fecal contamination in aquifers,
      limited research has been devoted to understanding the biological processes
      involved in the initial attachment of E. coli transported in abiotic porous
      media. The roles of the various surface structures of E. coli, like
      lipopolysaccharides (LPS), autotransporter proteins, and fimbriae are unknown.
      The objective of this research was to establish the effects of variations in
      surface characteristics of the outer membrane of E. coli on the attachment
      efficiency of 54 E. coli strains upon transport in saturated quartz sand under
      identical flow conditions. We used column experiments to assess retention of the
      E. coli strains, and we determined sphericity, motility, zeta-potential, and
      aggregation of all strains. LPS composition was determined based on known
      serotypes, and the presence/absence of 22 genes encoding surface characteristics
      was determined with qualitative PCR. The results indicated that under identical
      flow conditions, there was a variation of two orders of magnitude in the maximum
      breakthrough concentrations of the 54 E. coli strains. Of all factors we
      investigated, no single factor was able to explain attachment efficiency
      variations statistically significantly. However, low attachment efficiencies were
      associated (p=0.13) with LPS containing saccharides with phosphate and/or
      carboxyl groups. These saccharide groups are acidic and likely charged with a
      negative O-atom, which reduced attachment to the negatively charged quartz
      surface. In addition, of the 22 genes tested, Afa was most associated (p=0.21)
      with attachment efficiency. The work presented here bridges knowledge on colloid
      transport and molecular microbiology, and tries to offer a more holistic view on
      the attachment of planktonic E. coli bacteria to (abiotic) quartz grain surfaces.
      Future research should involve the use of microbiological techniques in order to
      be able to map the unique or grouped characteristics of E. coli in aquifers, and
      to assess the usefulness of E. coli as a fecal indicator in aquifers.

PMID- 19765794
TI  - Synthesis of 2-deoxy-hexopyranosyl derivatives of uridine as donor substrate
      analogues for glycosyltransferases.
AB  - A series of 2-deoxy-hexopyranosyl derivatives of uridine have been synthesized as
      analogues of UDP-sugar. These compounds were tested as inhibitors against bovine
      beta-1,4-galactosyltransferase I in fluorescent assays and showed no significant
      inhibition.

PMID- 19765795
TI  - Bio-polymer adsorbent for the removal of malachite green from aqueous solution.
AB  - A simple, economical and green methodology has been developed for the adsorption
      of malachite green using cellulose powder as the adsorbent. Batch experimental
      procedures were conducted to investigate the adsorption ability of this bio
      polymer to remove malachite green from aqueous medium. The adsorbed dye on
      cellulose was characterized by Fourier transform-infrared spectroscopy (FT-IR).
      The various analytical parameters such as the effect of contact time, pH,
      temperature, etc. were optimized. The adsorption was efficient at a neutral pH
      (7.2) and both Langmuir and Freundlich isotherm models showed good fit into the
      experimental data. The adsorption kinetics indicated that the adsorption proceeds
      according to pseudo-second-order model. The adsorption of malachite green was
      found to be exothermic and it was accompanied by decrease in the entropy. Column
      studies were performed and the regeneration of the adsorbent was done easily
      using environmentally benign polyethylene glycol-400.

PMID- 19765796
TI  - Treatment of chromite ore processing residue by pyrolysis with rice straw.
AB  - Chromite Ore Processing Residue (COPR) is the byproduct of chromate production
      process, which contains a large amounts of Cr(VI). The present work developed a
      new technique to treat COPR, and the process involved mixing the COPR with rice
      straw followed by pyrolysis. It was found that the gaseous organic fraction
      generated during pyrolysis of straw was beneficial to Cr(VI) reduction. In the
      study, process variables, such as the amount of straw added to COPR, heating
      temperature and particle size, were systematically varied, and their influences
      on the Cr(VI) reduction in COPR were all investigated. After pyrolysis, Cr(VI)
      decreased greatly, from 3400 for untreated COPR to less than 30 mg kg(-1) for
      treated COPR at 600 degrees C.

PMID- 19765797
TI  - Fate of cadmium in activated sludge after changing its physico-chemical
      properties by thermal treatment.
AB  - The effect of thermal treatment of activated sludge on cadmium uptake was
      investigated in respect with potential modifications of floc surface properties.
      Soluble fraction biochemical composition and floc size measurements evidenced
      floc destructuration and the release of (in)organic ligands in solution.
      Characterization of sludge samples by potentiometric titrations and IR spectra
      showed the transfer of functional groups from particulate to soluble fraction as
      well as the higher availability of phosphate groups originating from cell
      membrane phospholipids after thermal treatment. Batch biosorption tests
      demonstrated that cadmium uptake was highly affected by sludge modifications due
      to thermal treatment. For temperatures below 95 degrees C, floc size decrease
      allowed a better availability of binding sites, resulting in a higher sorption
      capacity. At temperatures above 95 degrees C, the effect of released soluble
      ligands and of the lower total number of surface functional groups limited
      cadmium uptake. Uptake mechanisms were also affected by sludge thermal treatment
      as surface complexation involving ion exchange tends to become predominant over
      precipitation.

PMID- 19765798
TI  - Evaluation of a peat moss plus soybean oil (PMSO) technology for reducing
      explosive residue transport to groundwater at military training ranges under
      field conditions.
AB  - An evaluation of peat moss plus crude soybean oil (PMSO) for mitigation of
      explosive contamination of soil at military facilities was performed using large
      soil lysimeters under field conditions. Actual range soils were used, and two
      PMSO preparations with different ratios of peat moss:soybean oil (1:1, PO1; 1:2,
      PO2) were compared to a control lysimeter that received no PMSO. PMSO was applied
      as a 10 cm layer on top of the soil, and Composition B detonation residues from a
      55-mm mortar round were applied at the surface of each of the lysimeters.
      Dissolution of the residues occurred during natural precipitation events over the
      course of 18 months. Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) emanating from
      the Composition B residues were significantly reduced by the PO2 PMSO material
      compared to the untreated control. Soil pore water RDX concentrations and RDX
      fluxes were reduced over 100-fold compared to the control plots at comparable
      depths. Residual RDX in the soil profile was also significantly lower in the PMSO
      treated plots. PO1 PMSO resulted in lower reductions in RDX transport than the
      PO2 PMSO. The transport of the RDX breakdown product hexahydro-1-nitroso-3,5
      dinitro-1,3,5-triazine (MNX) was also greatly reduced by the PMSO materials.
      Results were in general agreement with a previously developed fate and transport
      model describing PMSO effectiveness. These results demonstrate the potential
      effectiveness of the inexpensive and environmentally benign PMSO technology for
      reducing the subsurface loading of explosives at training ranges and other
      military facilities.

PMID- 19765799
TI  - Heavy metal desorption kinetic as affected by of anions complexation onto
      manganese dioxide surfaces.
AB  - Oxides of Fe, Al, and Mn have been studied extensively for heavy metals fixation
      in soil. However, little is known about the effect of anions on the desorption
      processes of these metals, especially from manganese dioxide. The purpose of this
      study was to examine the influence of residence time, temperature, and
      interacting anions on desorption of Pb(2+), Cd(2+) and Cu(2+) from MnO(2). MnO(2)
      was characterized by different experimental techniques prior to desorption
      studies. The sorption-desorption studies were conducted for Pb(2+), Cu(2+), and
      Cd(2+) ions in the presence of different electrolytes and at different
      temperature in the range 293-323 K. For all the sorption experiments, Pb(2+)
      sorption was the greatest and almost 100% sorption occurred in the presence of
      0.001 M potassium phosphate. The sorption of metals under investigation followed
      the order Pb(2+)>Cu(2+)>Cd(2+), whereas the desorption order was
      Cd(2+)>Cu(2+)>Pb(2+) in 0.01 M potassium nitrate and sulphate. Only a small
      quantity of desorbed Pb was detected, even at the low value of pH 3. These
      results indicated the stability of lead phosphate precipitates or that phosphate
      treatment imparted stability to the ternary complexes formed at the MnO(2)
      surface. The detailed desorption kinetics were conducted only for Cd(2+) in 0.01
      M potassium nitrate or 0.001 M phosphate at pH values of 3 and 4 in the
      temperature range 303-323 K. A substantial decrease in Cd(2+) desorption was
      noted with increasing pH and temperature and the desorption process reached
      equilibration in 3h at pH 4. However, at pH 3 the desorption fluctuated, which is
      probably due the dissolution of the solid at such low pH values.

PMID- 19765800
TI  - Possibilities and limitations of equilibrium sampling using polydimethylsiloxane
      in fish tissue.
AB  - Polydimethylsiloxane (PDMS) has been used for passive equilibrium sampling in
      numerous abiotic environmental matrices. Recently, this approach was extended to
      lipid-rich tissue. This work investigated the possibilities and limitations of
      using PDMS thin-film extraction for in tissue equilibrium sampling in fish
      species of varying lipid content. Polychlorinated biphenyls (PCBs) were used as
      model lipophilic organic pollutants. PDMS thin-films were inserted in intact fish
      tissue for differing time periods (1h up to 1 week). The thin-films were then
      solvent-extracted and the extracts were analyzed using gas chromatography coupled
      to mass spectrometry. Whether equilibrium had been established was investigated
      either by using PDMS thin-films of multiple thicknesses (140-620 microm) or by
      assessing kinetics by means of time series. Equilibration was found to be rapid
      (i.e. in the range of hours) in lipid-rich fish whereas equilibrium was not
      achieved within one week in tissues with low or medium lipid content (i.e. up to
      2% lipids). Regarding lipid-rich fish, the newly developed method was found to be
      sufficiently sensitive to determine equilibrium partitioning concentrations of
      PCBs in lipids of samples from the Baltic Sea, and it is a promising approach for
      any kind of fatty tissue.

PMID- 19765801
TI  - Overexpression of YKL-40 is an independent prognostic marker in gastric cancer.
AB  - YKL-40 is a growth factor for connective tissue cells and a migration factor for
      endothelial cells. Elevated serum level of YKL-40 has been associated with poor
      prognosis in many cancers. However, the status of YKL-40 expression and its
      clinical/prognostic significance in gastric cancer are unclear. In this study,
      the expression of YKL-40 was studied by immunohistochemistry in gastric cancer
      tissue microarray containing 172 primary gastric cancer cases and 70 adjacent
      nonneoplastic mucosa specimens. The correlations between YKL-40 expression and
      clinicopathologic features, as well as activation of PI3K/Akt pathways were
      addressed. Expression of YKL-40 was significantly higher in gastric cancer
      tissues than that in adjacent nonneoplastic tissues. Overexpression YKL-40 was
      found in 28.4% of gastric cancers and was significantly associated with tumor
      invasion (P = .007) and lymph node metastasis (P = .009). For survival study,
      overexpression of YKL-40 was significantly associated with worse outcome (P =
      .001). When known clinical variables were added to a multivariate analysis, TNM
      stage, tumor size, and overexpression of YKL-40 emerged as independent prognostic
      factors. Further study indicated that the oncogenic function of YKL-40 might be
      through the activation of Akt pathway. These results suggest that overexpression
      of YKL-40 is correlated with the aggressive behavior of tumor cells, which could
      be used as an independent molecular marker for the predicting poor prognosis of
      patients with gastric cancer.

PMID- 19765802
TI  - Comparative functional morphology of the primate peroneal process.
AB  - The first metatarsal of living Primates is characterized by a well-developed
      peroneal process, which appears proportionally larger in prosimians than in
      anthropoids. A large peroneal process has been hypothesized to: 1) reflect
      powerful hallucal grasping, 2) act as a buttress to reduce strain from loads
      acting on the entocuneiform-first metatarsal joint during landing and grasping
      after a leap, and/or 3) correlate with differences in physiological abduction of
      the hallux. In this study, we address the latter two hypotheses by comparing the
      morphology of the peroneal process in 143 specimens representing 37 species of
      extant prosimians, platyrrhine anthropoids, and tupaiids (tree shrews) that
      engage in different locomotor behaviors. In particular, we compare taxa that vary
      in leaping frequency and hallucal abduction. Linear and angular measurements on
      the first metatarsal were obtained to evaluate differences in relative peroneal
      process thickness and length, first metatarsal abduction angle, and overall first
      metatarsal shape. Leaping frequency was significantly correlated only with
      relative peroneal process thickness within extant lorisoids. Relative process
      length was positively correlated with the angle of hallucal abduction within
      prosimians; this angle is significantly greater in prosimians than anthropoids.
      Multivariate analyses of metatarsal shape effectively separate species along
      phylogenetic lines, but not by locomotor behaviors. The hypothesis that the
      peroneal process on the first metatarsal reduces the loads on the entocuneiform
      first metatarsal joint during landing after a leap is in part supported by data
      from extant lorisoids (i.e., slow quadrupedal lorises vs. leaping galagos). A
      peroneal process of greater length within prosimians may serve to increase the
      lever arm for the peroneus longus muscle in order to prevent hyper-abduction,
      followed by inversion in locomotor situations where the animal's weight is born
      on a highly divergent/abducted hallux.

PMID- 19765803
TI  - A simple model for screening the local impacts of atmospheric ammonia.
AB  - The dry deposition of ammonia from the atmosphere to the surface can lead to
      eutrophication of sensitive ecosystems and acidification of the soil. A large
      proportion of the ammonia emitted from agricultural sources can be deposited
      within a few kilometres and, therefore, impacts of ammonia dry deposition often
      occur near to the source. To assess these impacts, short-range atmospheric
      dispersion models are often applied to simulate the emission, dispersion and
      deposition of ammonia. However, these models can be time-consuming to run and
      often require detailed input data and, therefore, for multiple assessments it is
      useful to have a method of screening to discard scenarios where impacts are
      expected to be negligible. The SCAIL model (Simple Calculation of Ammonia Impact
      Limits) has been developed for this purpose. SCAIL estimates the atmospheric
      concentration and dry deposition at the nearest edge of a sensitive ecosystem
      (receptor) downwind of an ammonia source. These estimates are calculated based on
      simple meteorological data, the emission rate of the source, land cover type and
      distance to the receptor. Analysis of the model predictions showed that
      uncertainty in the model input data leads to an uncertainty in concentration and
      dry deposition estimates of 25-30% and 40-45% respectively. Detailed atmospheric
      dispersion models will also have similar uncertainties since they use similar
      types of input data. Comparison of the concentration predictions with previous
      measurements made around eight farms showed that the model significantly
      underestimated concentrations although the model performance was similar to
      existing screening techniques. The measurement dataset was used to calibrate the
      SCAIL model which subsequently performed better, using independent verification
      data, than existing models calibrated in a similar way. The benefits of the SCAIL
      model are already being seen in the UK, where it is used to screen farms for
      potential impacts on statutory nature conservation areas.

PMID- 19765804
TI  - Lead and cadmium levels of commonly administered pediatric syrups in Nigeria: a
      public health concern?
AB  - Fifty different pediatric syrups were randomly sampled from patent medicine
      stores and pharmaceutical shops within Awka, in Anambra State between November
      2007 and May 2008. Syrups were ashed before digestion using conc. aqua regia,
      HCl:HNO(3) (3:1) and lead and cadmium were assayed with AAS 205A. Results
      revealed that 60 and 98% of the sample size had lead and cadmium respectively.
      The lead levels ranged from 0.01 in chloroquine to 1.08 mg/l in magcid
      suspension. The highest level of cadmium was seen in magcid suspension with
      concentration of 2.45 mg/l while lowest concentration of 0.01 in emzolyn and
      colipan. About 41.2% of the locally made syrup had none detectable levels of lead
      while all the syrup had detectable levels of cadmium. Lead levels ranged from
      0.01 mg/l in cadiphen manufactured in Dholka, India to 0.09 in maxiquine made in
      England. About 68.8% of the imported syrups of the imported syrups had non
      detectable levels of lead. Chloramphenicol and zentel albendazole syrups had 0.60
      and 0.88 mg/l of cadmium respectively. Bellis cough syrup showed the lowest level
      (0.01 mg/l) of cadmium. Only erythromycin suspension representing 6.3% had non
      detectable level of cadmium of the imported syrups. Due to the Cd and Pb levels
      found, we suggest that the behaviour scenario (here, self administration without
      medical assistance) should be properly taken under control. Along with this,
      contamination sources or vulnerable practices during syrups preparation should be
      also assessed in a tiered approach, towards the minimization of noxious presence
      in syrups and the promotion of quality of Nigerian-made products.

PMID- 19765805
TI  - Decadal and seasonal scale changes of an artificial lake environment after
      blocking tidal flows in the Yeongsan Estuary region, Korea.
AB  - Artificial lakes, initially built in estuaries for positive purposes such as
      flood prevention and providing irrigation water, have been found to have negative
      impacts including blocking tidal cycles, disappearance of brackish water zones,
      sediment increase, water pollution, change of microbial diversity inhabiting
      patterns, and a decline in fish diversity. In this study, multidisciplinary field
      studies including physical, chemical, and biological analyses were performed to
      demonstrate decadal and seasonal scale changes in the ecological environment in
      Yeongsan Reservoir (YSR), Korea, since the construction of a 4.35 km-long dam in
      1981. The results of the study show that the volume of sediment accumulated in
      YSR was 75.2 million m(3) since the dam was constructed, resulting in a 33.6%
      reduction of the total water storage capacity. Also, water quality in YSR was
      affected by complex physico-chemical and hydrological phenomena, including saline
      and thermal stratifications, and pollutant loadings leading to eutrophication.
      Subsequent sediment bacteria analyses showed microbial diversity according to
      different depths in sediment, indicating the environmental change of sediment
      ecology. Moreover, the fish diversity in this study (2006-2007) was found to be
      considerably reduced compared to a similar study in 1989 (42% reduction), and the
      ecological health was deemed to be in a "poor" condition based on the 10-metric
      Lentic Ecosystem Health Assessment (LEHA) model. Accordingly, these results
      indicate that aquatic ecosystems are detrimentally affected by estuarine dams
      that block tidal flows, and when applied to short/long-term management strategies
      for artificial lakes in estuaries, suggest that similar construction projects
      have to be suitably controlled.

PMID- 19765806
TI  - Practice pattern for postoperative management of endometrial cancer in Japan: a
      survey of the Japanese Gynecologic Oncology Group.
AB  - OBJECTIVE: To determine the current status of postoperative management of
      endometrial cancer in Japan by surveying members of the Japanese Gynecologic
      Oncology Group (JGOG). METHOD: We conducted an original mail survey regarding the
      status of postoperative treatment including indication criteria, treatment
      procedures, and chemotherapeutic regimen among all 226 active member institutions
      of the JGOG. RESULTS: A total of 199 institutions (88.1%) responded to the
      survey. A total of 4063 patients with endometrial cancer were treated at the
      member institutions of the JGOG over a year. As adjuvant therapy, chemotherapy
      (79.9%) was significantly (p<0.01) preferred over radiotherapy (13.0%) or
      hormonal therapy (7.1%). Furthermore, more than 50% of respondent institutions
      performed adjuvant therapy when patients exhibited International Federation of
      Gynecology and Obstetrics (FIGO) stage IB/G3/positive lymph-vascular space
      invasion (LVSI)/endometrioid adenocarcinoma or FIGO IB/G3/non-endometrioid
      histology, and more than 90% institutions administered adjuvant therapy when
      patients exhibited FIGO IC/G3/positive LVSI/endometrioid adenocarcinoma or FIGO
      stage IC/G3/regardless of LVSI/non-endometrioid histology. A combination of
      paclitaxel and carboplatin was the most preferred first-line regimen for adjuvant
      chemotherapy followed by combination regimens consisting of anthracycline and
      platinum. CONCLUSION: The present survey provides relevant information regarding
      the current status of adjuvant therapy in Japanese patients with endometrial
      cancer.

PMID- 19765807
TI  - Robotic-assisted laparoscopic hysterectomy and lymphadenectomy for endometrial
      cancer: Analysis of surgical performance.
AB  - OBJECTIVES: To provide an objective analysis of surgical performance of robotic
      assisted laparoscopic hysterectomy (RALH) with lymphadenectomy for endometrial
      cancer during the learning phase of the procedure and to assess opportunities for
      improvement. METHODS: From July 2006 to March 2008, 100 patients with endometrial
      cancer underwent RALH with lymphadenectomy using the da Vinci Robotic Surgical
      System. Data were analyzed for operative time (OT), estimated blood loss (EBL),
      length of stay (LOS), intra-operative complications, surgical-pathologic factors,
      and post-operative complications using an intent-to-treat analysis. A comparison
      of the data on a quartile (Q) basis was performed for the 100 RALH cases and
      separately for the 65 cases that had a complete pelvic-and-aortic lymphadenectomy
      (PAL). RESULTS: Age and body mass index (BMI) did not change significantly during
      the study. More grade 3 tumors were treated in the last 50 cases (22% vs. 10%,
      p<0.05). Stage III tumors were identified in 18.7% cases in Q2-4 and none in Q1
      (p<0.05). The number of patients undergoing complete PAL and the number of aortic
      lymph nodes (LN) removed per case increased each quarter. There were 4 (4%)
      conversions to laparotomy. Delayed vaginal cuff healing decreased from 16% in Q1
      to 0% in Q3-4. No case required blood transfusion. Comparing first 10 cases to
      the last 10 cases, the total LN counts increased from 15 to 21 nodes, the aortic
      LN counts increased from 4.7 to 8.0, and the OT decreased from 203 to 160 min.
      Intra-surgeon analysis revealed an improvement in the total LN yields from first
      50 to second 50 cases for each surgeon. CONCLUSIONS: Operative times decreased
      and aortic dissections improved with increasing LN counts during the first 100
      cases of RALH. Furthermore, patient safety and improvement in surgical
      performance was demonstrated.

PMID- 19765808
TI  - VEGFR-2 silencing by small interference RNA (siRNA) suppresses LPA-induced
      epithelial ovarian cancer (EOC) invasion.
AB  - BACKGROUND: The VEGF-VEGF receptor (VEGFR) signaling axis has emerged as a
      promising target for cancer therapy, attributing to its vital role in tumor
      angiogenesis and growth. We have previously reported the regulation of epithelial
      ovarian cancer (EOC) invasion and migration by VEGF and the implication of VEGF
      VEGFR-2 axis in lysophosphatidic acid (LPA)-induced EOC invasion. However, the
      expression profile of VEGF and VEGFRs in EOC, their association with tumor
      aggressiveness, and their regulation by LPA remain unclear. OBJECTIVES AND
      METHODS: In this study, we examined the expression of VEGFR-1, VEGFR-2,
      neuropilin-1 (NRP-1), NRP-2, VEGF(121), and VEGF(165) in established EOC cell
      lines and assessed their correlation with cell invasiveness. Moreover, using an
      ovarian cancer tissue qPCR array, we analyzed VEGFR-2 expression across a panel
      of 48 tissues with different disease stages and histological grades. We also
      tested the effect of LPA on VEGF and VEGFR-2 expression and examined whether
      blocking VEGFR-2 by RNA interference (RNAi) affects LPA-induced EOC invasion.
      RESULTS: We show that VEGF and VEGFR-2 expression correlates with cell
      invasiveness and VEGFR-2 expression in ovarian cancer tissues correlate with
      tumor grade. In addition, LPA, at 20 muM, significantly induced the expression of
      VEGF(121), VEGF(165), and VEGFR-2 in SKOV3 and DOV13 cells (P<0.05). VEGFR-2
      small interference RNA (siRNA) transfection remarkably decreased LPA's invasion
      promoting effect (P<0.001) in SKOV3 cells without significantly decreasing SKOV3
      cells' basal invasiveness. In DOV13 cells, VEGFR-2 silencing significantly
      decreases both the basal level cell invasion and LPA's invasion promoting effect
      (P<0.001). CONCLUSION: These results suggest that decreasing VEGFR-2 expression
      by RNAi may prove to be an effective method to reduce the metastatic potential of
      EOC cells exposed to elevated levels of LPA.

PMID- 19765809
TI  - Survival after intestinal perforation: can it be predicted?
AB  - OBJECTIVE: Intestinal perforation is associated with high morbidity and mortality
      in gynecologic oncology patients. We investigated potential factors associated
      with survival after perforation which may influence treatment recommendations.
      METHODS: A retrospective review of all gynecologic oncology patients experiencing
      intestinal perforation between 1993 and 2007 was performed. Demographics, cancer
      history, presenting symptoms, vital signs, laboratory values, and management of
      perforation were collected, and Acute Physiology and Chronic Health Evaluation II
      (APACHE II) scores were calculated for each patient. Factors affecting survival
      from the time of perforation were analyzed using Kaplan-Meier method and
      univariate and multivariate Cox proportional hazard models. Student's t-test and
      chi(2) analysis were also utilized to evaluate potential associations. RESULTS:
      Fifty-three patients met the inclusion criteria. No difference in survival was
      found based on disease site, history of radiation therapy, presenting symptoms,
      smoking history, or presence of bowel procedures performed during the most recent
      abdominal surgery prior to perforation. APACHE II score, disease status, body
      mass index, and treatment method of perforation were found to be significant
      prognostic factors for survival. After multivariate Cox regression analysis, only
      APACHE II scores remained significantly associated with an increased risk of
      death. Median survival of patients with APACHE II scores <15 was 28.13 months
      compared to 2.90 months in patients with scores> or =15 (P<0.0001). CONCLUSION:
      Many factors must be examined when determining the management of intestinal
      perforation in gynecologic oncology patients. Clinicians should consider the
      APACHE II score in their assessment to assist risk stratification and treatment
      planning of these patients.

PMID- 19765810
TI  - A genome-wide RNAi screen for modifiers of the circadian clock in human cells.
AB  - Two decades of research identified more than a dozen clock genes and defined a
      biochemical feedback mechanism of circadian oscillator function. To identify
      additional clock genes and modifiers, we conducted a genome-wide small
      interfering RNA screen in a human cellular clock model. Knockdown of nearly 1000
      genes reduced rhythm amplitude. Potent effects on period length or increased
      amplitude were less frequent; we found hundreds of these and confirmed them in
      secondary screens. Characterization of a subset of these genes demonstrated a
      dosage-dependent effect on oscillator function. Protein interaction network
      analysis showed that dozens of gene products directly or indirectly associate
      with known clock components. Pathway analysis revealed these genes are
      overrepresented for components of insulin and hedgehog signaling, the cell cycle,
      and the folate metabolism. Coupled with data showing many of these pathways are
      clock regulated, we conclude the clock is interconnected with many aspects of
      cellular function.

PMID- 19765811
TI  - Trichostatin A affects histone acetylation and gene expression in porcine somatic
      cell nucleus transfer embryos.
AB  - Epigenetic aberrancies likely preclude correct and complete nuclear reprogramming
      after somatic cell nucleus transfer (SCNT) and may underlie the observed reduced
      viability of cloned embryos. In the current study, we tested the effects of the
      histone deacetylase-inhibitor trichostatin A (TSA) on preimplantation development
      and on histone acetylation and the gene expression of nucleus transfer (NT)
      porcine (Sus scrofa) embryos. Our results showed that 5 nM TSA for 26 h after
      reconstitution resulted in embryos (NTTSA) that reached the blastocyst stage at a
      higher level (48.1% vs. 20.2%) and increased number of cells (105.0 vs. 75.3)
      than that of the control (NTC) embryos. In addition, and unlike the NTC embryos,
      the treated embryos displayed a global acetylated histone H4 at lysine 8 profile
      similar to the in vitro-fertilized (IVF) and cultured embryos during the
      preimplantation development. Finally, we determined that several transcription
      factors exert a dramatic amount of genetic control over pluripotency, including
      Oct4, Nanog, Cdx2, and Rex01, the imprinting genes Igf2 and Igf2r, and the
      histone deacetyltransferase gene Hdac2. The NT blastocysts showed similar levels
      of Oct4, Cdx2, and Hdac2 but lower levels of Nanog than those of the IVF
      blastocyst. However, the NTTSA blastocysts showed similar levels of Rex01, Igf2,
      and Igf2r as those of IVF blastocysts, whereas the NTC blastocysts showed
      significantly lower levels for those genes. Our results suggest that TSA improves
      porcine SCNT preimplantation development and affects the acetylated status of the
      H4K8, rendering acetylation levels similar to those of the IVF counterparts.

PMID- 19765812
TI  - Assessment of plasma membrane and chromatin structure of sperm from transgenic
      and non-transgenic boars.
AB  - The aim of this study was to determine the apoptotic changes and chromatin damage
      in non-transgenic and transgenic boars carrying the human alpha1,2
      fucosyltransferase gene. Five ejaculates were collected from six transgenic (TG)
      and six non-transgenic (NTG) boars. Five ejaculates were collected from six
      transgenic (TG) and six non-transgenic (NTG) boars both crossbreds of Polish
      Landrace and Large White. Two fluorescence methods were employed to measure
      apoptosis: an assay to assess the early changes in sperm membrane integrity using
      fluorophore YO-PRO-1 and an assay for phosphatidylserine (PS) translocation
      across the plasma membrane using fluorescein-labeled Annexin-V. The chromatin
      damage was assessed based on the sperm chromatin structure assay method. No
      significant differences in the proportion of all detected subpopulations of
      spermatozoa were found between TG and NTG boars. Similarly, the analysis of the
      chromatin structure revealed no statistical differences in the sperm chromatin
      damage between TG and NTG boars. In conclusion, the presence of the human
      alpha1,2-fucosyltransferase gene in the genome of TG boars did not cause any
      spermatogenesis process disturbances leading to the increased production of
      apoptotic spermatozoa. Moreover, the low level of sperm with damaged chromatin in
      TG boars confirms the high stability of the spermatogenesis process in the TG
      boars analyzed.

PMID- 19765813
TI  - Disfluencies along the garden path: brain electrophysiological evidence of
      disrupted sentence processing.
AB  - Bailey and Ferreira (2003) hypothesized and reported behavioral evidence that
      disfluencies (filled and silent pauses) undesirably affect sentence processing
      when they appear before disambiguating verbs in Garden Path (GP) sentences.
      Disfluencies here cause the parser to "linger" on, and apparently accept as
      correct, an erroneous parse. Critically, the revision process usually associated
      with GP-disambiguating verbs does not appear to be triggered. In order to verify
      this effect, we recorded event-related potentials (ERPs) time-locked to
      disambiguating verbs in spoken GP sentences from 15 adults. A filled pause,
      silent pause, or no disfluency appeared before the GP-disambiguating verbs.
      Principal component analysis (PCA) revealed that fluent GP sentences elicited
      P600, an ERP index that revision of the initial parse was attempted. Crucially,
      P600 was attenuated for sentences containing a filled or silent pause before the
      GP-disambiguating verb. However, PCA detected an N400-like activation for these
      items, suggesting that listeners accepted the original (erroneous) parse and
      continued integrating at the verb; a conclusion that is tentative and requires
      further study. A left anterior positivity was also detected at GP-disambiguating
      verbs flanked by a filled pause. Discussion focuses on what these preliminary
      findings tell us about how oral comprehension proceeds when the time-course of
      sentence processing is disrupted.

PMID- 19765814
TI  - Intermittent preventive treatment of malaria in infancy.

PMID- 19765815
TI  - Protective efficacy and safety of three antimalarial regimens for intermittent
      preventive treatment for malaria in infants: a randomised, double-blind, placebo
      controlled trial.
AB  - BACKGROUND: Administration of sulfadoxine-pyrimethamine at times of vaccination
      intermittent preventive treatment in infants (IPTi)-is a promising strategy to
      prevent malaria. However, rising resistance to this combination is a concern. We
      investigated a shortacting and longacting antimalarial drug as alternative
      regimens for IPTi. METHODS: We undertook a double-blind, placebo-controlled trial
      of IPTi in an area of high resistance to sulfadoxine-pyrimethamine at sites of
      moderate (n=1280 infants enrolled) and low (n=1139) intensity of malaria
      transmission in Tanzania. Infants aged 8-16 weeks were randomly assigned in
      blocks of 16 to sulfadoxine (250 mg) plus pyrimethamine (12.5 mg; n=319 in
      moderate-transmission and 283 in low-transmission sites), chlorproguanil (15 mg)
      plus dapsone (18.75 mg; n=317 and 285), mefloquine (125 mg; n=320 and 284), or
      placebo (n=320 and 284), given at the second and third immunisations for
      diphtheria, pertussis, and tetanus, and for measles. Research team and child were
      masked to treatment. Recruitment was stopped early at the low-transmission site
      because of low malaria incidence. The primary endpoint was protective efficacy
      against all episodes of clinical malaria at 2-11 months of age. Analysis was by
      intention to treat. This study is registered with ClinicalTrials.gov, number
      NCT00158574. FINDINGS: All randomly assigned infants were analysed. At the
      moderate-transmission site, mefloquine had a protective efficacy of 38.1% (95% CI
      11.8-56.5, p=0.008) against clinical malaria in infants aged 2-11 months, but
      neither sulfadoxine-pyrimethamine (-6.7%, -45.9 to 22.0) nor chlorproguanil
      dapsone (10.8%, -24.6 to 36.1) had a protective effect. No regimen had any
      protective efficacy against anaemia or hospital admission. Mefloquine caused
      vomiting in 141 of 1731 (8%) doses given on day 1 (odds ratio vs placebo 5.50,
      95% CI 3.56-8.46). More infants died in the chlorproguanil-dapsone and mefloquine
      groups (18 and 15, respectively) than in the sulfadoxine-pyrimethamine or placebo
      groups (eight deaths per group; p=0.05 for difference between chlorproguanil
      dapsone and placebo). INTERPRETATION: IPTi with a longacting, efficacious drug
      such as mefloquine can reduce episodes of malaria in infants in a moderate
      transmission setting. IPTi with sulfadoxine-pyrimethamine has no benefit in areas
      of very high resistance to this combination. The appropriateness of IPTi should
      be measured by the expected incidence of malaria and the efficacy, tolerability,
      and safety of the drug. FUNDING: IPTi Consortium and the Gates Malaria
      Partnership.

PMID- 19765816
TI  - Efficacy and safety of intermittent preventive treatment with sulfadoxine
      pyrimethamine for malaria in African infants: a pooled analysis of six
      randomised, placebo-controlled trials.
AB  - BACKGROUND: Intermittent preventive treatment (IPT) is a promising strategy for
      malaria control in infants. We undertook a pooled analysis of the safety and
      efficacy of IPT in infants (IPTi) with sulfadoxine-pyrimethamine in Africa.
      METHODS: We pooled data from six double-blind, randomised, placebo-controlled
      trials (undertaken one each in Tanzania, Mozambique, and Gabon, and three in
      Ghana) that assessed the efficacy of IPTi with sulfadoxine-pyrimethamine. In all
      trials, IPTi or placebo was given to infants at the time of routine vaccinations
      delivered by WHO's Expanded Program on Immunization. Data from the trials for
      incidence of clinical malaria, risk of anaemia (packed-cell volume <25% or
      haemoglobin <80 g/L), and incidence of hospital admissions and adverse events in
      infants up to 12 months of age were reanalysed by use of standard outcome
      definitions and time periods. Analysis was by modified intention to treat,
      including all infants who received at least one dose of IPTi or placebo.
      FINDINGS: The six trials provided data for 7930 infants (IPTi, n=3958; placebo,
      n=3972). IPTi had a protective efficacy of 30.3% (95% CI 19.8-39.4, p<0.0001)
      against clinical malaria, 21.3% (8.2-32.5, p=0.002) against the risk of anaemia,
      38.1% (12.5-56.2, p=0.007) against hospital admissions associated with malaria
      parasitaemia, and 22.9% (10.0-34.0, p=0.001) against all-cause hospital
      admissions. There were 56 deaths in the IPTi group compared with 53 in the
      placebo group (rate ratio 1.05, 95% CI 0.72-1.54, p=0.79). One death, judged as
      possibly related to IPTi because it occurred 19 days after a treatment dose, was
      subsequently attributed to probable sepsis. Four of 676 non-fatal hospital
      admissions in the IPTi group were deemed related to study treatment compared with
      five of 860 in the placebo group. None of three serious dermatological adverse
      events in the IPTi group were judged related to study treatment compared with one
      of 13 in the placebo group. INTERPRETATION: IPTi with sulfadoxine-pyrimethamine
      was safe and efficacious across a range of malaria transmission settings,
      suggesting that this intervention is a useful contribution to malaria control.
      FUNDING: Bill & Melinda Gates Foundation.

PMID- 19765817
TI  - Magnetic resonance imaging of multifunctional pluronic stabilized iron-oxide
      nanoparticles in tumor-bearing mice.
AB  - We are investigating the magnetic resonance imaging characteristics of magnetic
      nanoparticles (MNPs) that consist of an iron-oxide magnetic core coated with
      oleic acid (OA), then stabilized with a pluronic or tetronic block copolymer.
      Since pluronics and tetronics vary structurally, and also in the ratio of
      hydrophobic (poly[propylene oxide]) and hydrophilic (poly[ethylene oxide])
      segments in the polymer chain and in molecular weight, it was hypothesized that
      their anchoring to the OA coating around the magnetic core could significantly
      influence the physical properties of MNPs, their interactions with biological
      environment following intravenous administration, and ability to localize to
      tumors. The amount of block copolymer associated with MNPs was seen to depend
      upon their molecular structures and influence the characteristics of MNPs.
      Pluronic F127-modified MNPs demonstrated sustained and enhanced contrast in the
      whole tumor, whereas that of Feridex IV was transient and confined to the tumor
      periphery. In conclusion, our pluronic F127-coated MNPs, which can also be loaded
      with anticancer agents for drug delivery, can be developed as an effective cancer
      theranostic agent, i.e. an agent with combined drug delivery and imaging
      properties.

PMID- 19765818
TI  - The treatment of established murine collagen-induced arthritis with a TNFR1
      selective antagonistic mutant TNF.
AB  - Blocking the binding of TNF-alpha to TNF receptor subtype-1 (TNFR1) is an
      important strategy for the treatment of rheumatoid arthritis (RA). We recently
      succeeded in developing a TNFR1-selective antagonistic TNF mutant, R1antTNF.
      Here, we report the anti-inflammatory effects of R1antTNF in a murine collagen
      induced arthritis model. To improve the in vivo stability of R1antTNF, we first
      engineered PEG (polyethylene glycol)-modified R1antTNF (PEG-R1antTNF). In
      prophylactic protocols, PEG-R1antTNF clearly improved the incidence, and the
      clinical score of arthritis due to its long plasma half-life. Although, the
      effect of PEG-R1antTNF on the incidence and production of IL1-beta was less than
      that of the existing TNF-blocking drug Etanercept, its effect on severity was
      almost as marked as Etanercept. Interestingly, in therapeutic protocols, PEG
      R1antTNF showed greater therapeutic effect than Etanercept. These data suggest
      that the anti-inflammatory effects of PEG-R1antTNF depend on the stage of
      arthritis. Recently, there has been much concern over the reactivation of viral
      infection caused by TNF blockade. Unlike Etanercept, PEG-R1antTNF did not
      reactivate viral infection. Together, these results indicate that selective
      inhibition of TNF/TNFR1 could be effective in treating RA and that PEG-R1antTNF
      could serve as a promising anti-inflammatory drug for this purpose.

PMID- 19765819
TI  - Gene delivery targeted to the brain using an Angiopep-conjugated
      polyethyleneglycol-modified polyamidoamine dendrimer.
AB  - Angiopep targeting to the low-density lipoprotein receptor-related protein-1
      (LRP1) was identified to exhibit high transcytosis capacity and parenchymal
      accumulation. In this study, it was exploited as a ligand for effective brain
      targeting gene delivery. Polyamidoamine dendrimers (PAMAM) were modified with
      angiopep through bifunctional PEG, then complexed with DNA, yielding PAMAM-PEG
      Angiopep/DNA nanoparticles (NPs). The angiopep-modified NPs were observed to be
      internalized by brain capillary endothelial cells (BCECs) through a clathrin- and
      caveolae-mediated energy-depending endocytosis, also partly through
      marcopinocytosis. Also, the cellular uptake of the angiopep-modified NPs were
      competed by angiopep-2, receptor-associated protein (RAP) and lactoferrin,
      indicating that LRP1-mediated endocytosis may be the main mechanism of cellular
      internalization of angiopep-modified NPs. And the angiopep-modified NPs showed
      higher efficiency in crossing blood-brain barrier (BBB) than unmodified NPs in an
      in vitro BBB model, and accumulated in brain more in vivo. The angiopep-modified
      NPs also showed higher efficiency in gene expressing in brain than the unmodified
      NPs. In conclusion, PAMAM-PEG-Angiopep showed great potential to be applied in
      designing brain-targeting drug delivery system.

PMID- 19765820
TI  - Dynamic shear-influenced collagen self-assembly.
AB  - The ability to influence the direction of polymerization of a self-assembling
      biomolecular system has the potential to generate materials with extremely high
      anisotropy. In biological systems where highly-oriented cellular populations give
      rise to aligned and often load-bearing tissue such organized molecular scaffolds
      could aid in the contact guidance of cells for engineered tissue constructs (e.g.
      cornea and tendon). In this investigation we examine the detailed dynamics of
      pepsin-extracted type I bovine collagen assembly on a glass surface under the
      influence of flow between two plates. Differential Interference Contrast (DIC)
      imaging (60x-1.4NA) with focal plane stabilization was used to resolve and track
      the growth of collagen aggregates on borosilicate glass for 4 different shear
      rates (500, 80, 20, and 9s(-1)). The detailed morphology of the collagen
      fibrils/aggregates was examined using Quick Freeze Deep Etch (QFDE) electron
      microscopy. Nucleation of fibrils on the glass was observed to occur rapidly
      (approximately 2 min) followed by continued growth of the fibrils. The growth
      rates were dependent on flow in a complex manner with the highest rate of axial
      growth (0.1 micro/s) occurring at a shear rate of 9s(-1). The lowest growth rate
      occurred at the highest shear. Fibrils were observed to both branch and join
      during the experiments. The best alignment of fibrils was observed at
      intermediate shear rates of 20 and 80s(-1). However, the investigation revealed
      that fibril directional growth was not stable. At high shear rates, fibrils would
      often turn downstream forming what we term "hooks" which are likely the combined
      result of monomer interaction with the initial collagen layer or "mat" and the
      high shear rate. Further, QFDE examination of fibril morphology demonstrated that
      the assembled fibrillar structure did not possess native D-periodicity. Instead,
      fibrils comprised a collection of generally aligned, monomers which were self
      assembled to form a fibril-like aggregate. In conclusion, though constant shear
      rate clearly influences collagen fibrillar alignment, the formation of highly
      organized collagenous arrays of native-like D-banded fibrils remains a challenge.
      Modulation of shear in combination with surface energy patterning to produce a
      highly-aligned initial mat may provide significant improvement of both the fibril
      morphology and alignment.

PMID- 19765821
TI  - The role of nanoparticle concentration-dependent induction of cellular stress in
      the internalization of non-toxic cationic magnetoliposomes.
AB  - Magnetoliposomes (MLs), built up of ultrasmall iron oxide cores each individually
      surrounded by a lipid bilayer, have emerged as highly biocompatible nanoparticles
      and promising tools in many biomedical applications. To improve cell uptake,
      cationic amphiphiles are inserted into the ML coat, but this often induces
      cytotoxic effects. In the present work, we synthesized and tested a cationic
      peptide-lipid conjugate (dipalmitoylphosphatidylethanolamine-succinyl-tetralysine
      [DPPE-succ-(Lys)4]) which is entirely composed of biodegradable moieties and
      specifically designed to exert minimal cytotoxic effects. Uptake studies with
      both murine 3T3 fibroblasts and C17.2 neural progenitor cells shows 95.63 +/-
      5.83 pg Fe and 87.46 +/- 5.62 pg Fe per cell after 24 h, respectively, for 16.66%
      DPPE-succ-(Lys)4-containing MLs, with no effect on cell viability. However, these
      high intracellular nanoparticle concentrations transiently affect actin
      cytoskeleton architecture, formation of focal adhesion complexes and cell
      proliferation, returning to control levels after approximately 7 days post ML
      incubation in both cell types. This study points out the great need for thorough
      characterization of cell-nanoparticle interactions as subtle time-dependent
      effects are hard to monitor and commonly used viability and functionality assays
      are not sufficient to address the broad spectrum of possible interferences of the
      nanoparticle with normal cell functioning.

PMID- 19765822
TI  - Persistence of antimicrobial activity through sustained release of triclosan from
      pegylated silicone elastomers.
AB  - Microbial adhesion to silicone elastomer biomaterials is a major problem often
      resulting in infection and medical device failure. Several strategies have been
      employed to modulate eukaryotic cell adhesion and to hamper bacterial adherence
      to polymeric biomaterials. Chemical modification of the surface by grafting of
      polyethylene glycol (PEG) chains or the incorporation of non-antibiotic
      antimicrobial agents such as triclosan into the biomaterial matrix may reduce
      bacterial adhesion. Here, such strategies are simultaneously applied to the
      preparation of both condensation-cure and addition-cure silicone elastomer
      systems, seeking a sustained release antimicrobial device biomaterial. The
      influence of triclosan incorporation and degree of pegylation on antimicrobial
      release, surface microbial adherence and persistence (Escherichia coli and
      Staphylococcus epidermidis) were evaluated in vitro. Non-pegylated silicone
      elastomers provided an increased percentage release of triclosan extending over a
      relatively short duration (99% release by day 64) compared with their pegylated
      (4% w/w) counterparts (65% and 72% release by day 64, for condensation and
      addition-cure systems respectively). Viable E. coli adherence to a non-pegylated
      silicone elastomer containing 1% w/w triclosan was reduced by over 99% after 24 h
      compared to the non-pegylated silicone elastomer containing no triclosan. No
      viable S. epidermidis adhered to any of the triclosan-loaded (>0.1% w/w)
      formulations other than the control. Persistence of the antimicrobial activity of
      the triclosan-loaded pegylated silicone elastomers continued for at least 70 days
      compared to the triclosan-loaded non-pegylated elastomers (at least 49 days).
      Understanding how PEG affects the release of triclosan from silicone elastomers
      may prove useful in the development of a biomaterial providing prolonged,
      effective antimicrobial activity.

PMID- 19765823
TI  - Design and activity of multifunctional fibrils using receptor-specific small
      peptides.
AB  - We have designed multifunctional peptide fibrils using bioactive laminin-derived
      peptides and evaluated their potential as a biomedical material for tissue
      engineering. The Leu-Arg-Gly-Asp-Asn (LRGDN) peptide derived from laminin-111,
      which contains an RGD sequence bound to integrin alphavbeta3, was added to the N
      terminus of the four amyloidogenic cell-adhesive laminin-derived peptides (A119:
      LSNIDYILIKAS, AG97: SAKVDAIGLEIV, B133: DISTKYFQMSLE, and B160: VILQQSAADIAR).
      The RGD-conjugated peptides were stained with Congo red and exhibited amyloid
      like fibril formation in the electron microscopic. The RGD-conjugated peptides
      promoted human dermal fibroblasts spreading with well-organized actin stress
      fibers and focal contacts. Human dermal fibroblast attachment to the RGD
      conjugated peptides was inhibited by anti-alphav integrin antibody. Further, cell
      attachment to B133 was inhibited by anti-alpha2 and anti-beta1 integrin
      antibodies, whereas attachment to RGD-B133 was inhibited by anti-alphav and anti
      beta1 integrin antibodies. These results suggest that the RGD-conjugated peptides
      interact with integrin alphavbeta3 and that RGD-B133 interacts with both integrin
      alphavbeta3 and integrin beta1. The RGD-conjugated peptide fibrils promoted
      neurite outgrowth in a peptide-dependent manner. These results support that
      biologically active sequence-conjugated peptide fibrils interact in a receptor
      specific manner with cells and promote multifunctional activities. These fibrils
      may have use as biological supports for cell-specific tissue engineering.

PMID- 19765824
TI  - DBA-lectin reactivity defines natural killer cells that have homed to mouse
      decidua.
AB  - During normal mouse pregnancy, abundant numbers of uterine natural killer (uNK)
      cells differentiate at implantation sites and contribute to early, post
      implantation endometrial angiogenesis and to spiral arterial modification. Mouse
      uNK cells are confidently recognized by light microscopy in tissue sections
      stained with special protocols. Classically, mouse uNK cells were identified as
      lymphocytes containing Periodic Acid Schiff's (PAS) reactive cytoplasmic
      granules. More recently, Dolichos biflorus lectin (DBA) reactions which stain not
      only the cytoplasmic granules but also the uNK cell membranes have been widely
      adopted. No lymphocytes in any tissues of virgin mice or external to the uterus
      of pregnant mice have DBA lectin reactivity equivalent to that of uNK cells;
      however, some uNK cells are now recognized as DBA-. Here, we describe a PAS/DBA
      lectin double staining protocol and assess the coincident staining of C57Bl/6J
      uNK cells from gestation day (gd)6, the first day of uNK cell abundance, to gd12,
      the day when Tunel+ nuclear senecence appears widely in uNK cells before their
      numerical decline. For these gd, PAS+ DBA- and PAS+DBA+ cells but not PAS-DBA+
      cells were identified. Dual positive cells increased from 47% at gd6 to 85% at
      gd12. Transplantation of normal bone marrow into alymphoid mice who were
      subsequently mated revealed the uterus repopulated by doubly reactive PAS+DBA+
      uNK cells (>95%). Thus, in normal pregnancies, most uNK cells appear to arise
      from progenitor cells that have homed to the uterus.

PMID- 19765825
TI  - Encouraging self-identified pedophiles and hebephiles to seek professional help:
      first results of the Prevention Project Dunkelfeld (PPD).

PMID- 19765826
TI  - Using a systems orientation and foundational theory to enhance theory-driven
      human service program evaluations.
AB  - This paper offers a framework for using a systems orientation and "foundational
      theory" to enhance theory-driven evaluations and logic models. The framework
      guides the process of identifying and explaining operative relationships and
      perspectives within human service program systems. Self-Determination Theory
      exemplifies how a foundational theory can be used to support the framework in a
      wide range of program evaluations. Two examples illustrate how applications of
      the framework have improved the evaluators' abilities to observe and explain
      program effect. In both exemplars improvements involved addressing and organizing
      into a single logic model heretofore seemingly disparate evaluation issues
      regarding valuing (by whose values); the role of organizational and program
      context; and evaluation anxiety and utilization.

PMID- 19765827
TI  - Validating self-reports of illegal drug use to evaluate National Drug Control
      Policy: a reanalysis and critique.
AB  - Illicit drug use remains at high levels in the U.S. The federal Office of
      National Drug Control Policy evaluates the outcomes of national drug demand
      reduction policies by assessing annual changes in drug use from several federally
      sponsored annual national surveys. Such survey methods, relying exclusively on
      drug use as self-reported on interviews or questionnaires, have been criticized
      by the United States Government Accountability Office as well as by independent
      experts, This paper critiques a major validity study of self-reported illicit
      drug use among youth commissioned by the federal government, showing that the
      favorable conclusions and summaries offered for public consumption are not
      warranted. Specifically, the findings of the validity study, which compared self
      reports with urine tests, are consistent with prior research showing that self
      reports substantially underestimate illicit drug use and can dramatically affect
      indicators of change. Thus, these national surveys are largely inadequate for
      evaluating national drug demand reduction policies and programs.

PMID- 19765828
TI  - Comorbidity of posttraumatic stress disorder, anxiety and depression: a 20-year
      longitudinal study of war veterans.
AB  - BACKGROUND: This study aims to: (a) follow-up the prevalence of comorbidity of
      posttraumatic stress disorder (PTSD), anxiety and depression; (b) determine the
      chronological relations between these disorder; and (c) examine whether PTSD
      comorbid with anxiety and depression is implicated in more impaired functioning
      than PTSD by itself. METHODS: 664 war veterans were followed up 1, 2, and 20
      years after their participation in the 1982 Lebanon War. Comorbidity was assessed
      by self reported PTSD, anxiety, and depression symptoms; impairment in
      psychosocial functioning was assessed by self reported problems in occupational,
      social, sexual and family functioning. RESULTS: At each point of assessment,
      rates of triple comorbidity (PTSD, anxiety and depression; 26.7-30.1%) were
      higher than rates of PTSD, either by itself (9.3-11.1%), or comorbid with
      depression (1.2-4.5%) or anxiety (2.9-4.5%). PTSD predicted depression, anxiety,
      and comorbid disorders, but not vice versa. At time 1 and 2 assessments, triple
      comorbidity was associated with more impaired functioning than PTSD alone. In
      addition, triple comorbidity at Time 2 was associated with more impaired
      functioning than double comorbidity. LIMITATIONS: Since measurements did not
      cover the entire span of 20 years since the war, the entire spectrum of changes
      could not be monitored. CONCLUSIONS: Almost one half of war veterans would
      endorse a lifetime triple comorbidity, and those who do, are likely to have more
      impaired functioning. The findings support the perspective that views PTSD as the
      dominant disorder following traumatic events, which impels the development of
      comorbid anxiety and depression.

PMID- 19765829
TI  - Cognitive deficits in the euthymic phase of unipolar depression.
AB  - Although neuropsychological deficits have been reported in patients with major
      depressive disorder (MDD) during an acute episode, relatively little is known
      about the persistence of these deficits in remission. This study investigated the
      performance of attention, executive function and verbal memory during remission
      from unipolar depressive episodes. We tested the hypothesis that outpatients do
      not differ in cognitive variables from controls. We did this using a well-defined
      outpatient sample, consisting of medicated and unmedicated patients, with a
      history of MDD. Ninety-seven subjects with MDD in remission ranging from young to
      old were compared with 97 healthy control subjects. Both samples were balanced
      for age, gender, and education levels. The Auditory Verbal Learning Test (AVLT)
      and the Trail Making Test (TMT) were used. Patients with remitted MDD, in
      comparison with controls, were impaired on tasks of attention, executive function
      and verbal memory. The individual level of depressive symptoms was not related to
      the cognitive performance. Small- to medium-sized significant correlations exist
      between cognitive test variables (as represented by Trail Making B and AVLT
      delayed recall) and level of depressive symptomatology (as measured by MADRS or
      BDI-II) in the total sample, indicating that higher levels of depressive
      symptomatology are associated with lower cognitive function. These findings
      suggest deficits in attention and delayed verbal recall can serve as an indicator
      for MDD in outpatients.

PMID- 19765831
TI  - Regulation of CXCL12 and CXCR4 expression by human brain endothelial cells and
      their role in CD4+ and CD8+ T cell adhesion and transendothelial migration.
AB  - Chemokines have emerged as important mediators of leukocyte recruitment to the
      CNS across the normally restrictive blood-brain barrier (BBB). In the present
      study we investigated the regulation of CXCL12 and its receptor, CXCR4,
      expression in human brain microvessel endothelial cells (HBMEC) and the effects
      of CXCL12 on the adhesion and migration of CD4+ and CD8+ T lymphocytes across
      HBMEC monolayers. Resting HBMEC constitutively expressed CXCL12 and CXCR4.
      Treatment with TNF-alpha, IFN-gamma, IL-1beta and LPS downregulated CXCL12 and
      CXCR4 expression and CXCL12 ligation induced internalization of CXCR4. The
      minimal adhesion and migration of CD4+ and CD8+ T lymphocytes across resting
      HBMEC were increased following cytokine treatment of HBMEC. CXCL12 gradients
      further enhanced adhesion of both T cell subsets to activated HBMEC and migration
      across resting monolayers. A greater number of CD8+ T lymphocytes adhered and
      migrated across activated HBMEC compared to CD4+ T cells. These studies provide
      insight into the regulation of CXCL12 and CXCR4 expression in cerebral EC and
      indicate an important role for CXCL12 in T cell subset recruitment across the BBB
      in CNS inflammation.

PMID- 19765830
TI  - Immune response in lung cancer mouse model mimics human anti-Hu reactivity.
AB  - Most patients with paraneoplastic encephalomyelitis/sensory neuronopathy PEM/SN
      have small-cell lung cancer (SCLC) and develop antibodies against neuronal
      specific Hu proteins, which are abnormally expressed in the tumor. Anti-Hu
      reactivity is present in ~16% of SCLC patients without PEM/SN. Here we test the
      hypothesis that engineered SCLC-prone mice may exhibit anti-Hu reactivity. We
      show that tumors from SCLC-prone mice misexpress Hu proteins, and 14% of mice
      harbor anti-Hu antibodies. Mice appear to show reactivity prior to clinical
      diagnosis of SCLC. This mouse model system will be useful to study SCLC
      associated autoimmunity, its diagnostic value, and the potential protective role
      of oncoantigen-directed autoantibodies.

PMID- 19765832
TI  - The role of Toll-like receptor 4 in eliciting acquired immune responses against
      nontypeable Haemophilus influenzae following intranasal immunization with outer
      membrane protein.
AB  - OBJECTIVE: Acute otitis media (AOM) is one of the most common infectious diseases
      in children. Nontypeable Haemophilus influenzae (NTHi) is considered a major
      pathogen in AOM. Current treatment options depend mainly on the use of
      antibiotics, thus developing vaccines to prevent this disease is an urgent goal
      for public health. Outer membrane proteins (OMPs) are promising candidate targets
      for vaccination against NTHi. METHODS: We used C3H/HeJ (Toll-like receptor 4
      [TLR4]-mutant) mice, which arose spontaneously and have a non-functional TLR4
      protein, and normal wild-type (WT) C3H/HeN mice. These mice were immunized
      intranasally with OMP from NTHi to investigate the mechanism of acquired immunity
      via TLR4. We examined the kinetics of mucosal and systemic antibody secretion and
      the migration of antibody producing lymphocytes to the mucosa in both strains
      during the course of intranasal immunization. RESULTS: The mucosal and systemic
      immune responses against OMP from NTHi were elicited in both TLR4-mutant and WT
      mice. However, the mucosal IgA, and systemic IgG, and Th1 immune responses in WT
      mice were stronger than those in TLR4-mutant mice. CONCLUSIONS: TLR4 plays an
      important role in relation to Th1 function for optimal development of the
      acquired immune responses to OMP administered intranasally. The variety of immune
      responses via TLR4 expression needs to be taken into consideration of individual
      vaccinations to prevent AOM.

PMID- 19765833
TI  - Changes in IGF-I, IGFBP-3 and ghrelin levels after adenotonsillectomy in children
      with sleep disordered breathing.
AB  - OBJECTIVE: The aim of this study was to determine the changes in insulin-like
      growth factor-I (IGF-I), insulin-like growth factor binding protein-3 (IGFBP-3)
      and ghrelin levels following adenotonsillectomy (T&A) in children with sleep
      disordered breathing (SDB). METHODS: Forty children (mean age 4.85+/-2.15 years)
      clinically diagnosed with adenotonsillar hypertrophy (ATH) related SDB were
      enrolled. All children underwent T&A. Serum levels of IGF-I, IGFBP-3 and ghrelin
      were measured before and 6 months after T&A. RESULTS: Serum levels of IGF-I and
      IGFBP-3 were significantly higher after T&A (p<0.001). Serum ghrelin levels
      showed a significant decrease after T&A (p<0.001). CONCLUSION: Children with ATH
      related SDB who underwent T&A showed significant increases in IGF-I and IGFBP-3
      levels indicating an increase in diurnal growth hormone secretion as well as a
      significant decrese in ghrelin levels indicating an increased oral food intake in
      the postoperative period.

PMID- 19765834
TI  - Looking BAC at striatal signaling: cell-specific analysis in new transgenic mice.
AB  - Understanding how molecular signaling pathways participate in behavioral
      responses requires determining precisely in which neuronal populations they are
      activated. The recent development of bacterial artificial chromosome (BAC)
      transgenic mice expressing a variety of reporters, epitope tagged-proteins or Cre
      recombinase driven by specific promoters, is a significant step forward in this
      direction. These mice help overcome the limitations of traditional approaches
      that examine an average of signaling events occurring in mixed populations of
      cells. Here, we review how recent studies using such tools have revisited the
      regulation of striatal signaling pathways, demonstrating the striking segregation
      between neurons expressing dopamine D1 and D2 receptors and significantly
      extending our overall knowledge of striatal neurons. Thus, BAC transgenic mice
      are changing the way to conceive experiments and provide an opportunity to fill
      the gaps between molecular and systems neurosciences.

PMID- 19765835
TI  - Metabolic brain networks in neurodegenerative disorders: a functional imaging
      approach.
AB  - Network analysis of functional brain imaging data is an innovative approach to
      study circuit abnormalities in neurodegenerative diseases. In Parkinson's
      disease, spatial covariance analysis of resting-state metabolic images has
      identified specific regional patterns associated with motor and cognitive
      symptoms. With functional imaging, these metabolic networks have recently been
      used to measure system-related progression and to evaluate novel treatment
      strategies. Network analysis is also being used to characterize specific
      functional biomarkers for Huntington's disease and Alzheimer's disease. These
      networks have been particularly helpful in uncovering compensatory mechanisms in
      genetically at-risk individuals. Ongoing developments in network applications are
      likely to enhance the role of functional imaging in the investigation of
      neurodegenerative disorders.

PMID- 19765836
TI  - Derivation and validation of a simple clinical risk-model in heart failure based
      on 6 minute walk test performance and NT-proBNP status--do we need specificity
      for sex and beta-blockers?
AB  - BACKGROUND: It is unclear whether risk prediction strategies in chronic heart
      failure (CHF) need to be specific for sex or beta-blockers. We examined this
      problem and developed and validated the consequent risk models based on 6-minute
      walk-test and NT-proBNP. METHODS: The derivation cohort comprised 636 German
      patients with systolic dysfunction. They were validated against 676 British
      patients with similar aetiology. ROC-curves for 1-year mortality identified cut
      off values separately for specificity (none, sex, beta-blocker, both). Patients
      were grouped according to number of cut-offs met (group I/II/III - 0/1/2 cut
      offs). RESULTS: Widest separation between groups was achieved with sex- and beta
      blocker-specific cut offs. In the derivation population, 1-year mortality was 0%,
      8%, 31% for group I, II and III, respectively. In the validation population, 1
      year rates in the three risk groups were 2%, 7%, 14%, respectively, after
      application of the same cut-offs. CONCLUSION: Risk stratification for CHF should
      perhaps take sex and beta-blocker usage into account. We derived and
      independently validated relevant risk models based on 6-minute-walk-tests and NT
      proBNP. Specifying sex and use of beta-blockers identified three distinct sub
      groups with widely differing prognosis. In clinical practice, it may be
      appropriate to tailor the intensity of follow-up and/or the treatment strategy
      according to the risk-group.

PMID- 19765837
TI  - Isolated pericardial hydatidosis as a cause of chest pain.
AB  - We report a case of isolated pericardial hydatidosis as a cause of chest pain.

PMID- 19765838
TI  - Sweet dreams might be bad.
AB  - Intermittent asystolia is a severe condition often associated with syncope. This
      42 year old man had episodes of asystolia up to 25s and denied any symptoms. He
      only reported sweet dreams during these occasions.

PMID- 19765839
TI  - Acute hyperkalemia and failure of pacemaker stimulus.
AB  - Acute hyperkalemia may induce well-known serious cardiac arrhythmia. However,
      ventricular aberration including concealed conduction may also occur. We report
      the case of a 35-year-old woman who had a previous history of late-operated
      ventricular septal defect communication and DDD pacemaker was admitted for
      dyspnea. During hospitalization, an acute hyperkalemia induced sinoatrial block
      despite correct pacemaker programming. Sodium bicarbonate allowed to restore
      sinus rhythm. Our report highlights that acute hyperkalemia may increase
      thresholds of pacemaker stimulus and physicians should be aware that complete
      block of conduction may occur despite correct pacemaker programming.

PMID- 19765840
TI  - Tricuspid annular respirophasic velocities in imminent tamponade.
AB  - A 57 year old woman, with newly diagnosed lung cancer and a large pericardial
      effusion in her echocardiogram, is presented in this case. No clinical or
      echocardiographic signs of tamponade physiology were initially detected. However,
      an excessive tricuspid annular respiratory fluctuation of the early diastolic
      velocity was noticed, which heralded the manifestation of overt tamponade on day
      5.

PMID- 19765841
TI  - Coronary artery ectasia and systolic flow cessation in a patient with
      hypertrophic cardiomyopathy: a case report.
AB  - Coronary artery ectasia (CAE) is characterized by diffuse or localized
      inappropriate dilation of coronary arteries and is often associated with slow
      coronary blood flow. Although CAE has been described to coexist with several
      clinical entities there are only three reports of CAE in the presence of
      hypertrophic cardiomyopathy (HCM). We report a case of CAE and slow coronary flow
      with systolic flow cessation in a 61-year old male with coronary artery disease
      and HCM.

PMID- 19765842
TI  - Diagnosis and definition of biventricular non-compaction associated to Ebstein's
      anomaly.
AB  - BACKGROUND: Non-compaction of ventricular myocardium is a rare congenital
      cardiomyopathy characterized by the presence of an extremely thickened
      endocardial layer with prominent trabeculations and deep recesses in
      communication with ventricular chamber and determining the typical spongeous
      aspect. The diagnosis of non-compaction of ventricular myocardium is possible
      through the identification of morphological alterations by echocardiographic
      evaluation. Ebstein's anomaly is a rare congenital cardiac disease, defined as
      the significant apical displacement of the part of the tricuspid valve causing
      significant tricuspid regurgitation and reduction of the functional right
      ventricle, right atrial and right ventricular dilatation and atrial and
      ventricular arrhythmias. CASE REPORT: We present a case of biventricular non
      compaction and Ebstein's anomaly in a 29-year-old Italian man that was referred
      for chest pain. Diagnosis of Ebstein's anomaly was made during a medical control
      for military service through an echocardiographic evaluation which left the
      suspicion of myocardium non-compaction. We present the cardiac image of the 2D
      and 3D eco, RMN, scintigraphy and ventriculaography.

PMID- 19765843
TI  - Estimating prevalence from targeted surveillance.

PMID- 19765844
TI  - Importance of technical operations: lessons from evolving biotherapeutics
      production methods.
AB  - Research and development connect technology and innovation to product design.
      However, the term is often used to refer to only a subset of the necessary
      disciplines to the exclusion of technical operations. Here, we argue that the
      importance of technical operations is undeniable, offering possible solutions by
      drawing on lessons from outdated biotherapeutics production methods and
      highlighting advances in the field.

PMID- 19765845
TI  - Dose-volume effects for normal tissues in external radiotherapy: pelvis.
AB  - A great deal of quantitative information regarding the dose-volume relationships
      of pelvic organs at risk has been collected and analysed over the last 10 years.
      The need to improve our knowledge in the modelling of late and acute toxicity has
      become increasingly important, due to the rapidly increasing use of inverse
      planned intensity-modulated radiotherapy (IMRT) and the consequent need of a
      quantitative assessment of dose-volume or biological-based cost functions. This
      comprehensive review concerns most organs at risk involved in planning
      optimisation for prostate and other types of pelvic cancer. The rectum is the
      most investigated organ: the largest studies on dose-volume modelling of rectal
      toxicity show quite consistent results, suggesting that sufficiently reliable
      dose-volume/EUD-based constraints can be safely applied in most clinical
      situations. Quantitative data on bladder, bowel, sexual organs and pelvic bone
      marrow are more lacking but are rapidly emerging; however, for these organs,
      further investigation on large groups of patients is necessary.

PMID- 19765846
TI  - Volumetric modulated arc therapy (VMAT) vs. serial tomotherapy, step-and-shoot
      IMRT and 3D-conformal RT for treatment of prostate cancer.
AB  - INTRODUCTION: Volumetric modulated arc therapy (VMAT), a complex treatment
      strategy for intensity-modulated radiation therapy, may increase treatment
      efficiency and has recently been established clinically. This analysis compares
      VMAT against established IMRT and 3D-conformal radiation therapy (3D-CRT)
      delivery techniques. METHODS: Based on CT datasets of 9 patients treated for
      prostate cancer step-and-shoot IMRT, serial tomotherapy (MIMiC), 3D-CRT and VMAT
      were compared with regard to plan quality and treatment efficiency. Two VMAT
      approaches (one rotation (VMAT1x) and one rotation plus a second 200 degrees
      rotation (VMAT2x)) were calculated for the plan comparison. Plan quality was
      assessed by calculating homogeneity and conformity index (HI and CI), dose to
      normal tissue (non-target) and D(95%) (dose encompassing 95% of the target
      volume). For plan efficiency evaluation, treatment time and number of monitor
      units (MU) were considered. RESULTS: For MIMiC/IMRT(MLC)/VMAT2x/VMAT1x/3D-CRT,
      mean CI was 1.5/1.23/1.45/1.51/1.46 and HI was 1.19/1.1/1.09/1.11/1.04. For a
      prescribed dose of 76 Gy, mean doses to organs-at-risk (OAR) were 50.69 Gy/53.99
      Gy/60.29 Gy/61.59 Gy/66.33 Gy for the anterior half of the rectum and 31.85
      Gy/34.89 Gy/38.75 Gy/38.57 Gy/55.43 Gy for the posterior rectum. Volumes of non
      target normal tissue receiving > or =70% of prescribed dose (53 Gy) were 337
      ml/284 ml/482 ml/505 ml/414 ml, for > or =50% (38 Gy) 869 ml/933 ml/1155 ml/1231
      ml/1993 ml and for > or =30% (23 Gy) 2819 ml/3414 ml/3340 ml/3438 ml /3061 ml.
      D(95%) was 69.79 Gy/70.51 Gy/71,7 Gy/71.59 Gy/73.42 Gy. Mean treatment time was
      12 min/6 min/3.7 min/1.8 min/2.5 min. CONCLUSION: All approaches yield treatment
      plans of improved quality when compared to 3D-conformal treatments, with serial
      tomotherapy providing best OAR sparing and VMAT being the most efficient
      treatment option in our comparison. Plans which were calculated with 3D-CRT
      provided good target coverage but resulted in higher dose to the rectum.

PMID- 19765847
TI  - Consequences of additional use of PET information for target volume delineation
      and radiotherapy dose distribution for esophageal cancer.
AB  - BACKGROUND AND PURPOSE: To determine the consequences of target volume (TV)
      modifications, based on the additional use of PET information, on radiation
      planning, assuming PET/CT-imaging represents the true extent of the tumour.
      MATERIALS AND METHODS: For 21 patients with esophageal cancer, two separate TV's
      were retrospectively defined based on CT (CT-TV) and co-registered PET/CT images
      (PET/CT-TV). Two 3D-CRT plans (prescribed dose 50.4 Gy) were constructed to cover
      the corresponding TV's. Subsequently, these plans were compared for target
      coverage, normal tissue dose-volume histograms and the corresponding normal
      tissue complication probability (NTCP) values. RESULTS: The addition of PET led
      to the modification of CT-TV with at least 10% in 12 of 21 patients (57%)
      (reduction in 9, enlargement in 3). PET/CT-TV was inadequately covered by the CT
      based treatment plan in 8 patients (36%). Treatment plan modifications resulted
      in significant changes (p<0.05) in dose distributions to heart and lungs.
      Corresponding changes in NTCP values ranged from -3% to +2% for radiation
      pneumonitis and from -0.2% to +1.2% for cardiac mortality. CONCLUSIONS: This
      study demonstrated that TV's based on CT might exclude PET-avid disease.
      Consequences are under dosing and thereby possibly ineffective treatment.
      Moreover, the addition of PET in radiation planning might result in clinical
      important changes in NTCP.

PMID- 19765848
TI  - Aortic distensibility indices and coronary flow velocity reserve in patients with
      different kinds of single-vessel coronary artery disease with versus without
      diabetes mellitus.

PMID- 19765849
TI  - Concurrent induction of necrosis, apoptosis, and autophagy in ischemic
      preconditioned human livers formerly treated by chemotherapy.
AB  - BACKGROUND/AIMS: Liver pathology induced by chemotherapy (steatosis or vascular
      injury) is known to increase the liver's sensitivity to ischemia/ reperfusion
      (I/R) injury, thereby increasing morbidity and mortality after liver resection.
      Our aim was to assess whether ischemic preconditioning (IP) reduces I/R injury to
      livers with chemotherapy-induced pathology. METHODS: We analyzed a series of
      livers from patients treated with chemotherapy for colorectal cancer who
      underwent IP (n=30) or not (n=31) before hepatectomy. All but one of the livers
      exhibited chemotherapy-induced steatosis and/ or peliosis before the I/R insult.
      RESULTS: Necrosis was less frequent (p=0.038) in livers with IP than in the
      others. IP had no influence on apoptosis as assessed by terminal transferase
      uridyl nick-end labeling (TUNEL) assay or caspase-3, -8 and -9 expression. IP
      induced a twofold increase in B-cell leukemia/ lymphoma 2 (Bcl-2; p<0.05), which
      was localized to hepatocytes of centrolobular and peliotic areas and colocalized
      with the autophagy protein beclin-1 in livers with IP, suggesting their
      coordinated role in autophagy. Increased expression of the phosphorylated Bcl-2
      was observed in preconditioned livers and was associated with a decreased
      immunoprecipitation of beclin-1 and the increased expression of light chain 3
      type II (LC3-II). The increased number of autophagic vacuoles seen by electron
      microscopy confirmed an association of autophagy in chemotherapy-injured livers
      following IP. However, the differences in protein expression were not reflected
      in postresection liver-injury tests or measure of patient morbidity. CONCLUSIONS:
      IP is associated with a reduction in necrosis of hepatocytes already damaged by
      chemotherapy and an activation of autophagy. Bcl-2 and beclin-1 could be major
      targets in the regulation of cell death during I/R injury.

PMID- 19765850
TI  - Soft drink consumption is associated with fatty liver disease independent of
      metabolic syndrome.
AB  - BACKGROUND/AIMS: The independent role of soft drink consumption in non-alcoholic
      fatty liver disease (NAFLD) patients remains unclear. We aimed to assess the
      association between consumption of soft drinks and fatty liver in patients with
      or without metabolic syndrome. METHODS: We recruited 31 patients (age: 43+/-12
      years) with NAFLD and risk factors for metabolic syndrome, 29 patients with NAFLD
      and without risk factors for metabolic syndrome, and 30 gender- and age-matched
      individuals without NAFLD. The degree of fatty infiltration was measured by
      ultrasound. Data on physical activity and intake of food and soft drinks were
      collected during two 7-day periods over 6 months using a food questionnaire.
      Insulin resistance, inflammation, and oxidant-antioxidant markers were measured.
      RESULTS: We found that 80% of patients with NAFLD had excessive intake of soft
      drink beverages (>500 cm(3)/day) compared to 17% of healthy controls (p<0.001).
      The NAFLD group consumed five times more carbohydrates from soft drinks compared
      to healthy controls (40% vs. 8%, p<0.001). Seven percent of patients consumed one
      soft drink per day, 55% consumed two or three soft drinks per day, and 38%
      consumed more than four soft drinks per day for most days and for the 6-month
      period. The most common soft drinks were Coca-Cola (regular: 32%; diet: 21%)
      followed by fruit juices (47%). Patients with NAFLD with metabolic syndrome had
      similar malonyldialdehyde, paraoxonase, and C-reactive protein (CRP) levels but
      higher homeostasis model assessment (HOMA) and higher ferritin than NAFLD
      patients without metabolic syndrome (HOMA: 8.3+/-8 vs. 3.7+/-3.7 mg/dL, p<0.001;
      ferritin: 186+/-192 vs. 87+/-84 mg/dL, p<0.01). Logistic regression analysis
      showed that soft drink consumption is a strong predictor of fatty liver (odds
      ratio: 2.0; p<0.04) independent of metabolic syndrome and CRP level. CONCLUSIONS:
      NAFLD patients display higher soft drink consumption independent of metabolic
      syndrome diagnosis. These findings might optimize NAFLD risk stratification.

PMID- 19765851
TI  - Context matters: where would you be the least worse off in the US if you were
      uninsured?
AB  - OBJECTIVES: We examined the health care access, quality, and cost experienced by
      uninsured Latino mothers in two communities in Minnesota and Texas. These
      communities differ substantially by the size of the local population without
      health insurance coverage. METHODS: Four focus groups were conducted with
      uninsured Latino mothers who were caring for at least one child in their
      household. Seventeen mothers participated in each community. All focus groups
      were conducted by the same trained staff from a non-profit, community-based
      research organization. RESULTS: Uninsured Latino mothers in Minnesota rated the
      quality of health care services in their community to be much higher than their
      Texas counterparts, but were more likely to emphasize the high costs of care and
      health insurance coverage. Participants in Texas also described having to go to
      Mexico to obtain health care services. CONCLUSIONS: Policies making provision for
      health care services to the uninsured are likely to be more effective when they
      take into account the context or composition of each specific local health care
      system as well as the financial and non-financial spillovers that these
      uninsurance-related contexts generate.

PMID- 19765852
TI  - Algorithm for hyperfast cone-beam spiral backprojection.
AB  - Cone-beam spiral backprojection is computationally highly demanding. At first
      sight, the backprojection requirements are similar to those of cone-beam
      backprojection from circular scans such as it is performed in the widely used
      Feldkamp algorithm. However, there is an additional complication: the
      illumination of each voxel, i.e. the range of angles the voxel is seen by the X
      ray cone is a complex function of the voxel position. The weight function has no
      analytically closed form and must be numerically determined. Storage of the
      weights is prohibitive since the amount of memory required equals the number of
      voxels per spiral rotation times the number of projections a voxel receives
      contributions and therefore is in the order of 10(9) to 10(11) floating point
      values for typical spiral scans. We propose a new algorithm that combines the
      spiral symmetry with the ability of today's 64 bit CPUs to store large amounts of
      precomputed weights. Using the spiral symmetry in this way allows to exploit data
      level parallelism and thereby to achieve a very high level of vectorization. An
      additional postprocessing step rotates these slices back to normal images. Our
      new backprojection algorithm achieves up to 24.6 Giga voxel updates per second
      (GUPS) on our systems that are equipped with two standard Intel X5570 quad core
      CPUs (Intel Xeon 5500 platform, 2.93 GHz, Intel Corporation). This equals the
      reconstruction of 410 images per second assuming each slice consists of 512 x 512
      pixels, receiving contributions from 512 projections.

PMID- 19765853
TI  - Survival after trimodality therapy for malignant pleural mesothelioma: Radical
      Pleurectomy, chemotherapy with Cisplatin/Pemetrexed and radiotherapy.
AB  - INTRODUCTION: The role of surgery in the management of malignant pleural
      mesothelioma (MPM) is controversial and there are no established guidelines. We
      describe the feasibility and long-term outcomes associated with Radical
      Pleurectomy (RP) as surgical therapy modality in a standardized trimodality
      therapy concept of MPM. METHODS: From November 2002 to October 2007, 35 out of
      102 consecutive patients with MPM were enrolled in our prospective database. They
      underwent trimodality therapy, including RP followed by 4 cycles of chemotherapy
      with Cisplatin (75 mg/m(2))/Pemetrexed (500 mg/m(2)) and radiotherapy 4-6 weeks
      after operation. RESULTS: Median age was 65 years. Nineteen patients were in
      advanced stages III and IV (54.3%). Tumor histology was epithelial in 27 patients
      (77.1%). Macroscopic complete resection could be achieved in 18 patients (51.4%).
      Surgical morbidity/mortality and trimodality treatment-related mortality were
      20.0%, 2.9% and 5.8%, respectively. Thirty-three patients completed the
      trimodality therapy. Median follow-up was 21.7 months. Overall median survival
      was 30.0 months. One-, 2-, and 3-year-survival were 69%, 50% and 31%,
      respectively. Advanced stages III/IV (p=0.06), macroscopic incomplete resections
      (p=0.001), non-epithelial histology (p=0.55) and nodal metastases (p=0.19) were
      associated with poorer survival. CONCLUSIONS: The trimodality therapy concept
      with RP demonstrates promising results in terms of long-term survival, morbidity
      and mortality. We propose that a surgical philosophy of limiting the procedure
      related morbidity while achieving comparable cytoreductive results allows
      patients to maintain physiological reserve to be eligible for multimodality
      treatment options in the long-term. The observed and theoretical benefits of this
      trimodality treatment approach warrant confirmation in larger RCT.

PMID- 19765854
TI  - Cannabinoids and experimental models of multiple sclerosis.
AB  - The inflammatory response is a hallmark in the development of autoimmune-mediated
      neurodegenerative diseases of the central nervous system (CNS). Research on these
      pathological phenomena is being extensively undertaken and experimental
      autoimmune encephalomyelitis (EAE) serves as a valuable animal model. Studies
      from this model have generated interesting insights into biological effects of
      cannabinoids and may, at least to a certain extent, reflect the cannabinoid
      mediated protective mechanisms also in human diseases with similar
      characteristics, such as multiple sclerosis (MS). Cannabinoids are involved in
      regulation of the immune system. These effects comprise modulation of
      inflammatory reaction through components of the innate and adaptive immune
      responses. Cannabinoids also confer neuroprotection and assist neuroregeneration,
      thus maintaining a balance within the delicate CNS microenvironment and restoring
      function following pathological condition, commonly driven by neuroinflammation.
      Continued studies of cannabinoid actions in EAE pathogenesis should be beneficial
      for the better understanding of the mechanisms governing such a vast array of
      physiological effects and in development of new therapeutic strategies for the
      treatment of human neuroinflammatory and neurodegenerative diseases.

PMID- 19765855
TI  - CD45 regulates thymocyte survival during development in fetal thymic organ
      culture.
AB  - The CD45 protein tyrosine phosphatase is essential for T cell development. Its
      external domain undergoes changes in glycosylation and isoform usage during
      thymocyte development, the consequences of which remain unknown. The contribution
      of this complex external domain to T cell development is unknown so we sought to
      examine the impact of CD45 engagement on T cell development. Treatment of
      wildtype fetal thymic organ cultures (FTOC) with certain CD45-specific monoclonal
      antibodies resulted in decreased thymocyte numbers specifically at the double
      positive and CD4 single positive stages of development. The decrease in thymocyte
      number correlated with increased annexinV staining, an early indicator of
      apoptotic death. In contrast, CD45-/- FTOC exhibited decreased cellularity and
      increased annexinV staining at all stages of development. Thymocyte selection, as
      assessed by CD5 expression on DP thymocytes, was not affected by anti-CD45
      treatment, whereas it was impaired in FTOC from CD45-deficient mice. The decrease
      in cellularity was not due to impaired proliferation as neither anti-CD45
      treatment nor CD45 deficiency resulted in decreased proliferation in FTOC. Thus,
      antibodies specific for the external domain of CD45 results in the selective
      impairment of thymocyte survival at specific stages of development, whereas CD45
      expression appears to be required for survival at all stages of development. Our
      studies show that CD45 expressed on thymocytes is an important regulator of
      survival during T cell development.

PMID- 19765856
TI  - Interferon-gamma-mediated pathways are induced in human CD34(+) haematopoietic
      stem cells.
AB  - Pro-inflammatory cytokines like interferon-gamma (IFN-gamma) are considered to be
      important in the development of anaemia of chronic disease (ACD). Both,
      inhibitory and stimulatory activities of IFN-gamma on erythropoiesis have been
      observed in vitro earlier. IFN-gamma induces several biochemical pathways in
      human monocytes, among them neopterin formation by GTP-cyclohydrolase I (GTP-CH
      I) and tryptophan degradation by the enzyme indoleamine 2,3-dioxygenase (IDO).
      IDO-mediated tryptophan deprivation efficiently inhibits the growth of
      proliferating cells and microbes, thus we wanted to examine whether enhanced
      tryptophan degradation by monocytic precursor cells also suppresses
      erythropoiesis. Therefore, IFN-gamma-mediated pathways were investigated in human
      CD34(+) progenitor cells, and effects of IFN-gamma on the proliferative activity
      of different progenitor subpopulations were studied. Cells were either cultivated
      in agar-conditioned medium (ACM) or in medium containing erythroid growth factors
      interleukin-3 (IL-3) and stem cell factor (SCF; EGFCM). Stimulation of CD34(+)
      cells with IFN-gamma in different doses (either 5000U/ml once or 200 and 400U/ml
      every other day) induced tryptophan degradation and in parallel also neopterin
      formation. Unstimulated cells cultured with ACM produced higher amounts of
      neopterin and kynurenine (all p<0.05). IFN-gamma stimulated higher kynurenine and
      neopterin formation in cells cultivated in EGFCM, stimulation with 400U IFN-gamma
      every other day was most effective. IFN-gamma stimulated the growth and
      proliferation of CFU-E and BFU-E (3-8) in both media. In conclusion, stimulation
      of haematopoietic stem cells with IFN-gamma activates IDO and neopterin
      formation, and it also exerts an influence on the proliferation of various stem
      cell populations.

PMID- 19765857
TI  - Arsenic response of AtPCS1- and CePCS-expressing plants - effects of external
      As(V) concentration on As-accumulation pattern and NPT metabolism.
AB  - Phytochelatins (PCs) are small, cysteine-rich peptides, known to play a major
      role in detoxification of both cadmium and arsenic. The aim of this study was to
      determine whether overexpression of either of two PC synthase (PCS) genes, AtPCS1
      and CePCS in Nicotiana tabacum (previously shown to cause decrease and increase,
      respectively, of cadmium tolerance of tobacco - Wojas et al., 2008) also
      contributes to such contrasting phenotypes with respect to arsenic (As) tolerance
      and accumulation, and how observed responses relate to non-protein thiol (NPT)
      metabolism. The expression of both genes resulted in an increase of As-tolerance,
      with CePCS plants most tolerant. We showed for the first time that the response
      of PCS overexpressing plants to As qualitatively depends on the external As(V)
      concentration. At the less toxic 50muM As(V), AtPCS1 and CePCS transformants
      accumulated more As in roots and leaves than WT. An increase in PC production and
      the level of PC2 species was detected in leaves of AtPCS1 and CePCS plants, which
      might explain their enhanced As-accumulation and tolerance. In contrast, at the
      highly toxic 200muM As(V), several disturbances in thiol metabolism of PCS
      overexpressing plants were found, surprisingly, including decrease of PC levels
      both in roots and leaves of transgenic plants relative to WT. The increase in As
      tolerance and accumulation due to AtPCS1 and CePCS overexpression, observed at
      the As(V) concentrations similar to those found in As-contaminated soils, makes
      these genes promising candidates for plant engineering for phytoremediation.

PMID- 19765858
TI  - Phosphorylation of mitogen-activated protein kinase (MAPK) is required for
      cytokinesis and progression of cell cycle in tobacco BY-2 cells.
AB  - The role of mitogen-activated protein kinase (MAPK) in plant cytokinesis remains
      largely uncharacterized. To elucidate its role, tobacco Bright Yellow-2 (BY-2)
      cells have been synchronized using a two-step procedure, and the different phases
      of the cell cycle identified by Histone 4 gene expression and the mitotic index.
      MAPK expression was analyzed by semi-quantitative (SQ) RT-PCR and protein gel
      blot analysis for phosphorylated MAPK during cell cycle progression. The SQ RT
      PCR analysis indicated that MAPK expression is lower in mitosis than in
      interphase (G1, G2 and S). However, the amount of phosphorylated MAPK remained
      stable throughout the cell cycle, indicating that MAPK activity is predominantly
      regulated at the post-translational level and that phosphorylation of MAPK plays
      an important role in mitosis. Application of the specific MAPK phosphorylation
      inhibitor U0126 revealed that while U0126 treatment decreases the phosphorylation
      of MAPK and the progression from telophase to early cytokinesis is significantly
      inhibited. The formation of the phragmoplast is also negatively affected at this
      stage. These results demonstrate that MAPK phosphorylation is involved in the
      formation of the cell plate within the phragmoplast during cytokinesis and that
      MAPK predominantly functions during the cytokinesis stage of the cell cycle in
      tobacco BY-2 cells.

PMID- 19765859
TI  - H1N1 influenza is here.
AB  - On 11 June WHO announced that the spread of H1N1 had reached pandemic phase 6.
      Since then countries around the world have increased their planning and
      preparedness for the continuing pandemic. Guidelines have been issued and
      circulated but confusion continues over their interpretation. We need to remind
      ourselves of the principles behind control measures and educate and reinforce
      standard infection control procedures in the acute hospital setting.

PMID- 19765860
TI  - A comprehensive surveillance, control and management programme for Clostridium
      difficile infection.

PMID- 19765861
TI  - Guidelines for prioritisation of single-room use: a pragmatic approach.

PMID- 19765862
TI  - Responsibility for managing healthcare-associated infections: where does the buck
      stop?
AB  - The prevention and control of healthcare-associated infections (HCAIs) requires a
      tripartite partnership between clinicians and carers, managers and
      government/Department of Health (DoH) across the whole health and social care
      community. Mandatory surveillance of meticillin-resistant Staphylococcus aureus
      bacteraemia and Clostridium difficile infection has shown a significant fall from
      peak numbers in 2003/04 and 2006, respectively, and there is now a zero tolerance
      approach to preventable infections and poor practice. Success so far has been
      based on senior management commitment, enhanced real-time surveillance,
      implementation of clinical protocols (high impact interventions, prudent
      prescribing), improved hand hygiene and environmental cleaning, and training and
      audit, backed up by a heightened performance management focus through targets and
      legislation (Code of Practice). DoH improvement teams have supported National
      Health Service trusts in implementing change. Responsibility for managing HCAI is
      a combination of managerial responsibility based upon compliance assurance that
      procedures and protocols are being implemented and personal professional
      responsibility of all clinicians and other healthcare workers.

PMID- 19765863
TI  - [Usefulness of the subcutaneous route in the care of patients with advanced
      dementia].
AB  - In advanced dementia, the therapeutic goals should be patient comfort, adequate
      symptom control, and the prevention of suffering due to futile, intrusive or
      disproportionate procedures. To attain these goals, the subcutaneous route is a
      useful tool, since it allows fluid administration and the delivery of many drugs.
      Because it is well tolerated and easy to apply, this route can be safely used in
      non-hospital settings, allowing patients to stay in their environment and
      avoiding the risks resulting from hospitalization. Although subcutaneous
      administration is outside the approved label of many drugs, clinical experience
      and the medical literature have produced sound evidence that has been
      incorporated into a number of practice guidelines in palliative care. The recent
      regulations simplify the implementation of these standards of clinical practice.

PMID- 19765864
TI  - [Chronic fatigue syndrome. Summary of the consensus document].

PMID- 19765865
TI  - [Description of registration of episodes of gender violence in medical records in
      the Principality of Asturias, Spain].
AB  - OBJECTIVE: To describe how episodes of gender violence notified to the Registro
      de Atencion Sanitaria en Violencia contra las Mujeres del Principado de Asturias
      (VIMPA) are registered in the clinical records of a health area of this
      geographical region. METHODS: We performed a cross-sectional, descriptive study
      in a sample of cases collected in the VIMPA Registry in 2005 and 2006. The
      variables analyzed were the way in which the episode of gender violence was coded
      and registered, the presence of antecedents, and the diagnostic agreement among
      documents. RESULTS: A total of 51.7% of primary care patients were attended in a
      center with access to their medical records. A specific International
      Classification of Primary Care-2 (World Organisation of National Colleges and
      Academics) code of abuse was used in only 15.1%, while a written diagnosis was
      used in all cases in specialized care. CONCLUSION: Episodes of gender violences
      were identified differently in distinct clinical documents. Our results point to
      the need for specific registries that would aid the combined use of distinct
      information sources.

PMID- 19765866
TI  - Synthesis and antimycobacterial activity of N'-[(E)-(monosubstituted
      benzylidene)]-2-pyrazinecarbohydrazide derivatives.
AB  - The present article describes a series of twenty-six N'-[(E)-(monosubstituted
      benzylidene)]-2-pyrazinecarbohydrazide (4-29), which were synthesized and
      evaluated for their cell viabilities in non infected and infected macrophages
      with Mycobacterium bovis Bacillus Calmette-Guerin (BCG). Afterwards, the non
      cytotoxic compounds (4, 6, 8, 15, 21, 23, 24, 27 and 28) were assessed against
      Mycobacterium tuberculosis ATCC 27294 using the micro plate Alamar Blue assay
      (MABA) and the activity expressed as the minimum inhibitory concentration (MIC)
      in microg/mL. The compounds 6, 23, 27 and 28 exhibited a significant activity (50
      100 microg/mL) when compared with first line drugs such as pyrazinamide and were
      not cytotoxic in their respective MIC values.

PMID- 19765867
TI  - Knee joint kinematics, kinetics and muscle co-contraction in knee osteoarthritis
      patient gait.
AB  - BACKGROUND: Compared to matched controls, knee osteoarthritis patients walk with
      altered, kinematics, kinetics and muscle activity. Studies of osteoarthritis
      patient gait have focused on individual measures, and findings from these studies
      differ due to differences in patient levels of disability and age. Therefore,
      aims of this study were to examine kinematic, kinetic and muscle co-contraction
      gait variables within a single osteoarthritis patient group, and to determine if
      alterations in these variables are related to pain, symptom and function
      measures. METHODS: Thirty asymptomatic controls and 54 patients with radiographic
      evidence of knee osteoarthritis participated. Self-perceived measures of pain and
      symptoms, and gait (knee joint angles, moments and muscle co-contraction) were
      analysed and compared. FINDINGS: Osteoarthritis patients had greater self
      perceived pain and symptoms on the questionnaires. Gait differences in the knee
      osteoarthritis patients were greater knee flexion at heel strike and during early
      stance along with reductions in the peak external knee extension moment in late
      stance. Co-contraction ratios highlighted greater lateral muscle activation in
      osteoarthritis patients, which were correlated with the magnitude of their
      adduction moments. Larger adduction moments were related to lower self-perceived
      pain and symptoms. INTERPRETATION: Osteoarthritis patients use predominantly
      lateral muscle activation during stance which may aid in stabilising the external
      knee adduction moment. Kinematic alterations in knee osteoarthritis patient gait
      occur without alterations in knee joint moments. Our results also suggest that
      adduction moments are lowered to reduce the patients' pain and symptoms.

PMID- 19765868
TI  - Bioanalytical characterisation of multiple endocrine- and dioxin-like activities
      in sediments from reference and impacted small rivers.
AB  - A comprehensive evaluation of organic contamination was performed in sediments
      sampled in two reference and three impacted small streams where endocrine
      disruptive (ED) effects in fish have been evidenced. The approach combined
      quantitative chemical analyses of more than 50 ED chemicals (EDCs) and a battery
      of in vitro bioassays allowing the quantification of receptor-mediated
      activities, namely estrogen (ER), androgen (AR), dioxin (AhR) and pregnane X
      (PXR) receptors. At the most impacted sites, chemical analyses showed the
      presence of natural estrogens, organochlorine pesticides, parabens, polycyclic
      aromatic hydrocarbons (16 PAHs), bisphenol A and alkylphenols, while synthetic
      steroids, myco-estrogens and phyto-estrogens were not detected. Determination of
      toxic-equivalent amounts showed that 28-96% of estrogenic activities in bioassays
      (0.2-6.3 ng/g 17beta-estradiol equivalents) were explained by 17beta-estradiol
      and estrone. PAHs were major contributors (20-60%) to the total dioxin-like
      activities. Interestingly, high PXR and (anti)AR activities were detected;
      however, the targeted analysed compounds could not explain the measured
      biological activities. This study highlighted the presence of multiple organic
      EDCs in French river sediments subjected to mixed diffuse pollution, and argues
      for the need to further identify AR and PXR active compounds in the aquatic
      environment.

PMID- 19765869
TI  - Mercury in urban soils with various types of land use in Beijing, China.
AB  - Mercury (Hg) concentration was investigated for 127 urban soil samples collected
      from business area (BA), classical garden (CG), culture and education area (CEA),
      public green space (PGS), residential area (RA) and roadside area (RSA) in
      Beijing. The median of Hg concentration in Beijing was 0.26 mg/kg. The value in
      CG was much higher than the other 5 types of land use, which was due to the
      historical use of Hg. More than 87% of the samples were not contaminated
      according to the guideline values of China, UK, Canada, and USEPA. Spatial
      distribution map revealed that Hg concentration showed a decreasing trend from
      the center to the suburb, it increased with the age of the urban area. Hg
      contamination in urban area of Beijing is marked by features of non-point sources
      associated with human activities, and it is most likely to be the common
      characteristics of Hg contamination in cities.

PMID- 19765870
TI  - Gentamicin-induced Bartter-like syndrome.

PMID- 19765871
TI  - Association of kidney function with coronary atherosclerosis and calcification in
      autopsy samples from Japanese elders: the Hisayama study.
AB  - BACKGROUND: Chronic kidney disease (CKD) is associated with increased risk of
      coronary heart disease. However, information regarding the histopathologic
      characteristics of coronary atherosclerosis in individuals with CKD is scarce.
      This study investigated the relationship between CKD and severity of coronary
      atherosclerosis in population-based autopsy samples. STUDY DESIGN: Cross
      sectional study. SETTING & PARTICIPANTS: 126 individuals randomly selected from
      844 consecutive population-based autopsy samples. PREDICTOR: Estimated glomerular
      filtration rate (eGFR) calculated using the 6-variable Modification of Diet in
      Renal Disease (MDRD) Study equation. OUTCOMES: Severity of atherosclerosis in 3
      main coronary arteries, including atherosclerotic lesion types defined using the
      American Heart Association classification; stenosis rates; and coronary calcified
      lesions. MEASUREMENTS: The relationship between CKD and severity of coronary
      atherosclerosis was evaluated using generalized estimating equation methods.
      RESULTS: Frequencies of advanced atherosclerotic lesions increased gradually as
      eGFR decreased (33.6%, 41.7%, 52.3%, and 52.8% for eGFRs > or = 60, 45-59, 30-44,
      and <30 mL/min/1.73 m(2), respectively; P for trend = 0.006). This relationship
      was substantially unchanged even after adjustment for potential confounding
      factors (ORs, 1.40 [95% CI, 0.76-2.55], 2.02 [95% CI, 0.99-4.15], and 3.02 [95%
      CI, 1.22-7.49] for eGFRs of 45-59, 30-44, and <30 mL/min/1.73 m(2),
      respectively). Frequencies of calcified lesions of coronary arteries also
      increased gradually with lower eGFRs (P for trend = 0.02). Hypertension and
      diabetes were associated with increased risk of advanced coronary atherosclerosis
      and calcification of coronary arteries in individuals with decreased eGFR.
      LIMITATIONS: Cross-sectional study, absence of data for proteinuria, and
      extremely high proportion of aged people. CONCLUSIONS: The autopsy findings
      presented here suggest that CKD is associated significantly with severity of
      coronary atherosclerosis. Patients with CKD should be considered a high-risk
      population for advanced coronary atherosclerosis.

PMID- 19765872
TI  - Ethnic density effects on maternal and infant health in the Millennium Cohort
      Study.
AB  - Studies have suggested that members of ethnic minority groups might be healthier
      when they live in areas with a high concentration of people from their own ethnic
      group - in spite of higher levels of material deprivation typically found within
      such areas. We investigated the effects of area-level same-ethnic density on
      maternal and infant health, independent of area deprivation and individual
      socioeconomic status, in five ethnic minority groups. The study was a cross
      sectional analysis within the UK Millennium Cohort Study and included mothers in
      five ethnic minority groups (Black African n=367, Bangladeshi n=369, Black
      Caribbean n=252, Indian n=462 and Pakistani n=868) and their 9-month-old infants.
      Outcome measures included: low birth weight, preterm delivery, maternal
      depression, self-rated health and limiting long-standing illness. Compared to
      those who live in areas with less than 5% of people from the same-ethnic minority
      population, Indian and Pakistani mothers were significantly less likely to report
      ever being depressed in areas with high same-ethnic density. There was a
      protective effect of ethnic density for limiting long-term illness among
      Bangladeshi mothers at 5-30% density and Pakistani mothers at all higher
      densities. Ethnic density was unrelated to infant outcomes and maternal self
      rated health, and unrelated to any outcomes in Black African and Black Caribbean
      mothers and infants, possibly because no families in these groups lived at higher
      levels of same-ethnic density. Results were similar whether we examined smaller
      or larger residential areas. We conclude that, among ethnic minority mothers and
      infants in England, the relationship of ethnic density to health varies by
      ethnicity and outcome. For some measures of maternal health, in some ethnic
      groups, the psychosocial advantages of shared culture, social networks and social
      capital may override the adverse effects of material deprivation.

PMID- 19765873
TI  - Gender and the associated impairments of childhood sexual abuse: a national study
      of Icelandic youth.
AB  - The current study used a national probability sample of 8618 Icelandic youth
      between the ages of 16 and 20 to examine the impairments associated with
      childhood sexual abuse for male and female victims. The dimensions of impairment
      were: general anxiety, eating anxiety, depressed mood, theft, and violent
      behavior. Overall, our results suggest that gender differences in impairment may
      depend on the particular outcome measured: (1) females were approximately three
      times more likely than males to experience childhood sexual abuse; (2) the
      association between childhood sexual abuse and subsequent depressed mood and
      general anxiety varied significantly by gender, with females more likely to
      experience these impairments; and (3) the associations between childhood sexual
      abuse and subsequent eating anxiety, theft, and violent behavior did not vary by
      gender.

PMID- 19765874
TI  - Parental education and children's online health information seeking: beyond the
      digital divide debate.
AB  - Research has shown that increasing numbers of teenagers are going online to find
      health information, but it is unclear whether there are disparities in the
      prevalence of online health seeking among young Internet users associated with
      social and economic conditions. Existing literature on Internet uses by adults
      indicates that low income, less educated, and minority individuals are less
      likely to be online health seekers. Based on the analysis of data from the Pew
      Internet and American Life Project for the US, this study finds that teens of low
      education parents are either as likely as or even more likely than teens of high
      education parents to seek online health information. Multiple regression analysis
      shows that the higher engagement in health seeking by teens of low education
      parents is related to a lower prevalence of parental Internet use, suggesting
      that some of these teens may be seeking online health information on behalf of
      their low education parents. Implications of these findings are discussed in
      relation to the issues of the digital divide and digital empowerment.

PMID- 19765875
TI  - 'Wellbeing': a collateral casualty of modernity?
AB  - In the now vast empirical and theoretical literature on wellbeing knowledge of
      the subject is provided mainly by psychology and economics, where understanding
      of the concept are framed in very different ways. We briefly rehearse these,
      before turning to some important critical points which can be made about this
      burgeoning research industry, including the tight connections between the
      meanings of the concept with the moral value systems of particular 'modern'
      societies. We then argue that both the 'science' of wellbeing and its critique
      are, despite their diversity, re-connected by and subsumed within the emerging
      environmental critique of modern consumer society. This places concerns for
      individual and social wellbeing within the broader context of global human
      problems and planetary wellbeing. A growing number of thinkers now suggest that
      Western society and culture are dominated by materialistic and individualistic
      values, made manifest at the political and social levels through the unending
      pursuit of economic growth, and at the individual level by the seemingly endless
      quest for consumer goods, regardless of global implications such as broader
      environmental harms. The escalating growth of such values is associated with a
      growing sense of individual alienation, social fragmentation and civic
      disengagement and with the decline of more spiritual, moral and ethical aspects
      of life. Taken together, these multiple discourses suggest that wellbeing can be
      understood as a collateral casualty of the economic, social and cultural changes
      associated with late modernity. However, increasing concerns for the environment
      have the potential to counter some of these trends, and in so doing could also
      contribute to our wellbeing as individuals and as social beings in a finite
      world.

PMID- 19765876
TI  - The individual and contextual pathways between oral health and income inequality
      in Brazilian adolescents and adults.
AB  - We evaluate the association between income inequality (Gini index) and oral
      health and in particular the role of alternative models in explaining this
      association. We also studied whether or not income at the individual level
      modifies the Gini effect. We used data from an oral health survey in Brazil in
      2002-2003. Our analysis included 23,568 15-19 and 22,839 35-44 year-olds nested
      in 330 municipalities. Different models were fitted using multilevel analysis.
      The outcomes analysed were the number of untreated dental caries (count), having
      at least one missing tooth (dichotomous) and being edentulous (dichotomous). To
      assess interaction as a departure from additivity we used the Synergy Index. For
      this, we dichotomized the Gini coefficient (high vs low inequality) by the median
      value across municipalities and the individual income in the point beyond which
      it showed roughly no association with oral health. Adjusted rate ratio of mean
      untreated dental caries, respectively for the 15-19 and 35-44 age groups, was
      1.12 and 1.16 for each 10 points increase in Gini scale. Adjusted odds ratio of a
      15-19 year-old having at least one missing tooth or a 35-44 year-old being
      edentulous was, respectively, 1.19 and 1.01. High income inequality had no
      statistically significant synergistic effect with being poor or living in a poor
      municipality. Higher levels of income inequality at the municipal level were
      associated with worse oral health and there was an unexplained residual effect
      after controlling for potential confoundings and mediators. Municipal level
      income inequality had a similar, detrimental effect, among individuals with lower
      or higher income.

PMID- 19765877
TI  - Willingness to pay for health insurance: an analysis of the potential market for
      new low-cost health insurance products in Namibia.
AB  - This study analyzes the willingness to pay for health insurance and hence the
      potential market for new low-cost health insurance product in Namibia, using the
      double bounded contingent valuation (DBCV) method. The findings suggest that 87
      percent of the uninsured respondents are willing to join the proposed health
      insurance scheme and on average are willing to insure 3.2 individuals (around 90
      percent of the average family size). On average respondents are willing to pay
      NAD 48 per capita per month and respondents in the poorest income quintile are
      willing to pay up to 11.4 percent of their income. This implies that private
      voluntary health insurance schemes, in addition to the potential for protecting
      the poor against the negative financial shock of illness, may be able to serve as
      a reliable income flow for health care providers in this setting.

PMID- 19765878
TI  - Can subjective and objective socioeconomic status explain minority health
      disparities in Israel?
AB  - Disparities in health exist between the three main population groups in Israel,
      non-immigrant Jews, immigrants from the former Soviet Union (arriving in Israel
      since 1990) and Arabs. This study examines the relationship between health and
      socioeconomic status in this multicultural population and assesses to what extent
      subjective and objective socioeconomic measures may explain the disparities in
      health. A random cross sectional telephone survey of 1004 Israelis aged 35-65 was
      performed. The questionnaire measured physical and mental health-related quality
      of life using the Short Form 12. Information regarding subjective socioeconomic
      status (SSS) and objective socioeconomic status (SES) was collected. Arabs and
      immigrant women from the former Soviet Union had worse physical health compared
      to non-immigrant Jews. Immigrant and Arab men and women had worse mental health
      compared to non-immigrant Jews. Multivariable log-linear regression analysis
      adjusting for age, SSS or SES explained the disparities in physical health
      between Arab and non-immigrant Jewish men. However, SSS and SES did not explain
      the disparities in physical health between the three groups of women. The
      disparities in mental health between immigrants and non-immigrant Jews can be
      explained by SSS for both men and women, whereas the disparities between Arabs
      and Jews can be explained by objective SES only among women. Employed men
      reported better physical and mental health. Part of the disparities in mental
      health in Israel can be attributed to differences in SSS and SES in the different
      groups. However, there is a need to identify additional factors that may add to
      the disparities in both physical and mental health. The disparities due to
      socioeconomic status vary by health measure and population group.

PMID- 19765879
TI  - Degrees of disclosure: a study of women's covert use of the diaphragm in an HIV
      prevention trial in sub-Saharan Africa.
AB  - In sub-Saharan Africa more women are infected with HIV/AIDS than men and new
      prevention methods are urgently needed. One major attribute of female-initiated
      HIV prevention methods is that they can be used covertly, without a male
      partner's knowledge. Using mixed methods, we explored the predictors and
      dimensions of covert use of the diaphragm in a randomized controlled trial that
      tested its effectiveness for HIV prevention. The Methods for Improving
      Reproductive Health in Africa (MIRA) trial was conducted in Zimbabwe and South
      Africa, and data collection took place between September 2003 and January 2007.
      This study is a secondary analysis of quantitative and qualitative data from
      participants randomized to the intervention group, and their male partners. It
      includes survey data from 2316 women (mean age=28.3), 14 focus group discussions
      (FGD) conducted with 104 women, and 7 FGD and 10 in-depth interviews with 37 male
      partners. The median follow-up for trial participation was 21 months (range: 12
      24). At their final visit, approximately 9% of women had never disclosed to their
      primary partners that they were using the diaphragm (covert use). In multivariate
      analysis, predictors of covert use included being older, not co-habiting with the
      partner, having a partner who did not use condoms, and being from South Africa.
      Qualitative analysis revealed that covert use was not dichotomous, but ranged
      along a continuum, which we categorized into five levels (i.e. full disclosure;
      mostly open use; occasional covert use; mostly covert use; and completely covert
      use). We discuss the critical role of the option of covert use for many women in
      the context of an HIV prevention trial, as well as gender power dynamics which
      may influence women's decisions about disclosure.

PMID- 19765882
TI  - [Broncho-angioplasty surgery in the treatment of lung cancer].

PMID- 19765880
TI  - What has fMRI told us about the development of cognitive control through
      adolescence?
AB  - Cognitive control, the ability to voluntarily guide our behavior, continues to
      improve throughout adolescence. Below we review the literature on age-related
      changes in brain function related to response inhibition and working memory,
      which support cognitive control. Findings from studies using functional magnetic
      resonance imaging (fMRI) indicate that processing errors, sustaining a cognitive
      control state, and reaching adult levels of precision, persist through
      adolescence. Developmental changes in patterns of brain function suggest that
      core regions of the circuitry underlying cognitive control are on-line early in
      development. However, age-related changes in localized processes across the
      brain, and in establishing long range connections that support top-down
      modulation of behavior, more effective neural processing for optimal mature
      executive function. While great progress has been made in understanding the age
      related changes in brain processes underlying cognitive development, there are
      still important challenges in developmental neuroimaging methods and the
      interpretation of data that need to be addressed.

PMID- 19765883
TI  - [Role of toll-like receptors in respiratory diseases].
AB  - There has been growing interest in the last 10 years in the study of innate
      immunity, in particular because of the possible role that toll-like receptors
      (TLR) may play in the pathogenesis of some respiratory disease such as for
      example, asthma, chronic obstructive pulmonary disease, and infections. TLR are a
      family of type 1 transmembrane proteins, responsible for recognizing molecular
      patterns associated with pathogens (PAMP, pathogen-associated molecular
      patterns), and expressed by a broad spectrum of infectious agents. This
      recognition leads to quick production of cytokines and chemokines which provides
      a long-lasting adaptive response to the pathogen. Currently, it is considered
      that the administration of drugs which modulate the activity of these receptors
      upwards or downwards may represent major therapeutic progress for handling these
      diseases. The aim of this review is to describe the different TLS, define their
      possible role in the pathogenesis of the main respiratory diseases and finally,
      speculate over the therapeutic possibilities which their modulation, agonist or
      antagonist, offers as possible therapeutic targets.

PMID- 19765884
TI  - The effect of multi-professional education on the recognition and outcome of
      patients at risk on general wards.
AB  - AIM: The aim of this study was to evaluate the effect of multi-professional full
      scale simulation-based education of staff on the mortality and staff awareness of
      patients at risk on general wards. DESIGN, SETTINGS AND PATIENTS: A prospective
      before-and-after study conducted on four general wards at Herlev Hospital,
      Denmark. In the pre-intervention period (June-July 2006) and post-intervention
      period (November-December 2007), all patients on the wards had vital signs
      measured in the evening by study personnel, who also asked nursing staff
      questions about patients with abnormal vital signs. The mortality of patients
      with abnormal vital signs was registered from the hospital database. Simplified
      medical emergency team calling criteria were used to define abnormal vital signs.
      INTERVENTION: In the intervention period (February-June 2007), 50% of medical and
      70% of nursing staff on the wards (app. 220 members of staff) were trained in a 1
      day multi-professional full-scale simulation-based course. RESULTS: In the pre-
      and post-intervention periods, 690 and 873 patients were included and of these
      129 and 155, respectively, had abnormal vital signs. No significant differences
      were observed between the pre- and post-intervention periods concerning the
      incidence of patients with abnormal vital signs (p=0.64), staff awareness of
      patients at risk (p=0.80), 30-day mortality (p=1.00), 180-day mortality (p=1.00)
      or length of hospital stay (p=0.11) among patients at risk. CONCLUSIONS: This
      multi-professional education of staff did not affect the rate of mortality or
      staff awareness of patients at risk on the wards.

PMID- 19765885
TI  - In the human urothelium and suburothelium, intradetrusor botulinum neurotoxin
      type A does not induce apoptosis: preliminary results.
AB  - BACKGROUND: Intradetrusor injections of botulinum neurotoxin type A (BoNTA) are
      emerging as the preferred second-line treatment for neurogenic and idiopathic
      overactive bladder (OAB). In animal experiments, intradetrusor BoNTA injections
      have been shown to cause apoptosis in the bladder urothelium and suburothelium
      but not the detrusor. OBJECTIVE: To investigate BoNTA-induced apoptosis in
      patients with refractory neurogenic OAB. DESIGN, SETTING, AND PARTICIPANTS:
      Twelve refractory OAB patients with neurogenic detrusor overactivity resulting
      from multiple sclerosis (MS) and seven controls were included prospectively.
      MEASUREMENTS: The number of apoptotic cells before and 4 wk after first
      intradetrusor BoNTA (300 U of BOTOX [Allergan, Irvine, CA, USA]) injections were
      estimated using terminal deoxynucleotidyl transferase-mediated dUTP nick-end
      labelling (TUNEL) staining. RESULTS AND LIMITATIONS: Comparison of TUNEL-positive
      cells (yes vs no) in the bladder urothelium and suburothelium revealed no
      significant differences in OAB patients before (4 of 12, 33%) versus after (3 of
      12, 25%) BoNTA treatment (p=0.99). In addition, no significant differences
      (p=0.99) were found in OAB patients versus controls. Because our findings are
      based on first intradetrusor BoNTA injections only, it is unclear whether the
      results could be extrapolated to repeat injections. CONCLUSIONS: In contrast to
      preliminary animal experiments, first intradetrusor BoNTA injections for treating
      refractory neurogenic OAB--a highly effective treatment--did not induce apoptosis
      in the bladder urothelium and suburothelium.

PMID- 19765886
TI  - The pathologist's mean grade is constant and individualizes the prognostic value
      of bladder cancer grading.
AB  - BACKGROUND: A new grading system for bladder cancer (BCa) was adopted in 2004 to
      reduce observer variability and provide better prognostic information. OBJECTIVE:
      We compared the World Health Organization (WHO) 1973 and 2004 systems for
      observer variability and prognosis. DESIGN, SETTING, AND PARTICIPANTS: Slides of
      173 primary non-muscle-invasive BCa were reviewed two times by four pathologists.
      MEASUREMENTS: Intra- and interobserver variability were assessed using kappa
      statistics. We determined the mean grade (eg, G1/low malignant potential is 1
      grade point, G2/low grade is 2 grade points) of the pathologists per grading
      cycle. Kaplan-Meier analyses were applied for prediction of recurrence and
      progression. RESULTS AND LIMITATIONS: For WHO 2004 and 1973 grading, the
      agreement between the pathologists was 39-74% (kappa: 0.14-0.58) and 39-64%
      (kappa: 0.15-0.41), respectively. The intraobserver agreement varied from 71% to
      88% (kappa: 0.55-0.81). The mean grade of a pathologist was constant (difference
      below 0.1 grade point) irrespective of the grading system. Conversely, mean-grade
      differences among the pathologists were high, up to 0.7 grade point. The mean
      grades for the WHO 2004 system were 0.3-0.5 grade point higher than those of WHO
      1973. Mean grade distinguished low and high graders among the pathologists and
      was strongly linked with risk of progression in each grade category. CONCLUSIONS:
      The variation in mean grade among individual pathologists exceeded the grade
      shift caused by WHO 2004 grading. Knowledge of the pathologist's mean grade
      allows a better assessment of the prognostic value of grading. Mean grade has the
      potential to become a tool for quality assurance in pathology.

PMID- 19765887
TI  - Stereotactic brain biopsy: Single center retrospective analysis of complications.
AB  - OBJECTIVE: Stereotactic biopsy is a widely used surgical technique for the
      histological diagnosis of intracranial lesions. Potential risks of this
      procedure, such as hemorrhage, seizure, and infection have been established, and
      different risk factors have been characterized. However, these risks have been
      addressed by only few studies conducted in Asian countries. MATERIALS AND
      METHODS: The study group is comprised of 299 consecutive stereotactic biopsy
      procedures by 11 neurosurgeons between 2004 and 2007. The pre-operative medical
      conditions, methods of biopsy and postoperative complications were analyzed.
      RESULT: The overall diagnostic yield was 90.64%. Complications were observed in
      7.36% of the cases, with symptomatic hemorrhages occurring in 4.35% of the cases,
      and the overall mortality rate in this study population was 1.34%. Patients with
      liver cirrhosis were at a higher risk of hemorrhage. Other clinical,
      radiological, or histological variables were not associated with an increased
      risk of complications. CONCLUSION: Stereotactic brain biopsy is a safe and
      reliable way to obtain a histological diagnosis. Based on our recent clinical
      experiences, the data suggests that more attention should be paid to liver
      cirrhotic patients, since the chance on hemorrhage is significantly larger.

PMID- 19765888
TI  - Sexsomnia: an uncommon variety of parasomnia.
AB  - Sexsomnia is considered a particular form of parasomnia characterized by atypical
      sexual behaviour during sleep. Only a few cases have been reported in the
      literature. We describe here two cases of sexsomnia that took place in adult
      women whose personal history was remarkable for traumatic sexual psychological
      stress during childhood. In addition, the first patient had a medical history of
      alcoholism during adolescence and current sleepwalking. In the second patient,
      drug consumption was reported during adolescence, and psychiatric assessment
      found a major depressive disorder. Neurological examination was normal for both
      patients. The sexual behaviour was reported by the bed partner because of total
      amnesia of the event by the patients. Events included moaning, vocalizations with
      dirty talk, masturbation, sexual assault, and sexual intercourse. The behaviour
      was harmful for the bed partner in the second case. For both patients,
      electroencephalogram and brain magnetic resonance imaging were normal whereas
      nocturnal polysomnography recordings revealed several abrupt and spontaneous
      arousals from slow-wave sleep. Patients were successfully treated by serotonin
      reuptake inhibitors. Our observations underline the fact that efforts need to be
      made to increase awareness of the issue of sexsomnia, in order to identify
      patients suffering from this atypical parasomnia, which can be associated with
      adverse psychological consequences and serious medico-legal issues.

PMID- 19765889
TI  - The effect of repeated administrations of granulocyte colony stimulating factor
      for blood stem cells mobilization in patients with progressive supranuclear
      palsy, corticobasal degeneration and multiple system atrophy.
AB  - Granulocyte colony stimulating factor (GCSF) may boost physiological stem cell
      repair system in patients with cerebral lesions. Atypical parkinsonisms (PSP,
      CBD, MSA) are characterized by rapidly progressive course without significant
      benefit from current therapies. We treated 11 patients with atypical parkinsonism
      (MSA n=4, PSP n=5, CBD n=2) with GCSF (5mcg/kg s.c. daily for 6 days/month) for 3
      months. We assessed CBC, CD34+ cells, routine biochemical and coagulation tests,
      UPDRS motor scores and safety. We did not observe significant adverse events
      during and following GCSF treatment. One patient withdrew informed consent. Three
      patients complained about bone pain that improved following steroid treatment.
      Four patients perceived a subjective benefit after treatment was completed. UPDRS
      motor score improved in three patients, remained stable in two and worsened in
      five. GCSF can be safely administered to patients with atypical parkinsonism and
      potentially meaningful clinical changes may be observed in some patients. These
      results are encouraging and warrant further studies.

PMID- 19765890
TI  - Cerebral microbleeds predict first-ever symptomatic cerebrovascular events.
AB  - OBJECTIVE: Cerebral microbleeds (CMB) on gradient-echo T2*-weighted magnetic
      resonance image (MRI) are frequently seen in patients with cerebral diseases. In
      this observational study we assessed whether CMB are a predictive factor for
      first-ever cerebrovascular events. PATIENTS AND METHODS: This study consisted of
      698 subjects without a history of symptomatic cerebrovascular events, who
      received gradient-echo T2*-weighted MRI for 3 months between November 2003 and
      January 2004 in Kishiwada City Hospital, Osaka, Japan. These subjects were then
      observed as outpatients for over 3.5 years. RESULTS: The prevalence of CMB at
      baseline was 17.0% (119/698) in this population, and the follow-up rate was 51%.
      A total of 36 first-ever symptomatic cerebrovascular events were observed during
      the 3 and a half-year follow-up period. First-ever symptomatic cerebrovascular
      events occurred significantly more frequently in subjects with CMB (15 cases)
      than those without CMB (21 cases) (p=0.001). Even after adjusting for age, sex
      and hypertension, it was revealed that the presence of CMB was an independent
      predictor for the first-ever symptomatic cerebrovascular event by using the Cox
      proportional hazards model (hazard ratio, 2.87; 95% CI, 1.27-6.48; p=0.01).
      CONCLUSION: The presence of CMB is an independent predictor of first-ever
      symptomatic cerebrovascular diseases.

PMID- 19765891
TI  - KG-135, enriched with selected ginsenosides, inhibits the proliferation of human
      prostate cancer cells in culture and inhibits xenograft growth in athymic mice.
AB  - Sun ginseng (SG) was recently developed as a heat-processed form of ginseng. The
      Rg3, Rk1, and Rg5 ginsenosides are its main ginsenoside components. SG has been
      reported to have more potent pharmacological activities than red ginseng (RG),
      where these pharmacological activities include vasodilatory, anti-oxidant and
      anti-tumorigenic effects. In the present study, we investigated KG-135, the
      ginsenoside-rich fraction of SG and demonstrated that this fraction inhibits
      proliferation of human prostate cancer cells both in vitro and in vivo. KG-135
      caused a significant growth inhibition of DU145 and PC-3 human prostate cancer
      cells. KG-135 induced cell cycle arrest in the G1 phase and caused an associated
      increase in the p21(Cip1) protein levels. When KG-135 was fed to mice that had
      been xenografted with DU145 tumors, a time-dependent inhibition of tumor growth
      was noted without any observed toxicity. Immunohistochemical analysis of the
      tumor tissues showed that KG-135 led to a decrease in the expression of
      proliferating cell nuclear antigen (PCNA). Microarray analysis of the tumors
      revealed that KG-135 inhibited tumor growth and also caused changes in the
      expression levels of multiple cancer-related genes. These data suggest that KG
      135 effectively inhibits prostate cancer cell proliferation. Its mechanism of
      action likely involves cyclin inhibition and regulation of the expression of the
      TNFRSF25 and ADRA2A genes.

PMID- 19765892
TI  - HSV-tk expressing mesenchymal stem cells exert bystander effect on human
      glioblastoma cells.
AB  - Previously we have reported adipose-tissue derived human mesenchymal stem cells
      (AT-MSC) as cellular delivery vehicles for tumor-targeted cancer gene therapy. In
      this report we aimed to determine whether Herpes simplex virus - thymidine kinase
      (HSV-tk) expressing AT-MSC (TK-MSC) could exert cytotoxic effect on tumor cells
      upon treatment with prodrug ganciclovir (GCV). Direct co-cultures of human
      glioblastoma cells 8-MG-BA, 42-MG-BA and U-118 MG with TK-MSC/GCV resulted in
      substantial viability decrease in vitro. This therapeutic paradigm was most
      efficient against 8-MG-BA glioblastoma cells exhibiting cytotoxicity (>50%) in
      the presence of TK-MSC and 0.1microM GCV. Rapid apoptosis induction in three
      glioblastoma cell lines and TK-MSC demonstrated both bystander cytotoxic effect
      on tumor cells and GCV conversion-mediated suicide effect on TK-MSC. Furthermore,
      we were able to demonstrate formation of gap junctions between AT-MSC and human
      glioblastoma cells as a mechanism contributing to bystander cytotoxicity.
      Inability of human HeLa and MCF7 to form gap junctions with AT-MSC rendered these
      cell refractory to the TK-MSC/GCV mediated cytotoxicity. Gap junction
      intercellular communication (GJIC) capability of AT-MSC with tumor cells further
      supports the exploitation of mesenchymal stem cells for approaches relying on the
      bystander effect. Biological consequences of these capabilities remain to be
      further explored.

PMID- 19765893
TI  - Separation, preconcentration and inductively coupled plasma-mass spectrometric
      (ICP-MS) determination of thorium(IV), titanium(IV), iron(III), lead(II) and
      chromium(III) on 2-nitroso-1-naphthol impregnated MCI GEL CHP20P resin.
AB  - A simple and effective method is presented for the separation and
      preconcentration of Th(IV), Ti(IV), Fe(III), Pb(II) and Cr(III) by solid phase
      extraction on 2-nitroso-1-naphthol impregnated MCI GEL CHP20P resin prior to
      their inductively coupled plasma-mass spectrometric determinations. The influence
      of analytical parameters including pH of the aqueous solution, flow rates of
      sample and eluent solutions and sample volume on the quantitative recoveries of
      analyte ions was investigated. Matrix effects caused by the presence of alkali,
      earth alkali and some metal ions in the analyzed solutions were investigated. The
      presented solid phase extraction method was applied to BCR-144R Sewage Sludge
      (domestic origin), BCR-141R Calcareous Loam Soil, NIST 1568a Rice Flour and NIST
      1577b Bovine Liver certified reference materials (CRMs) for the determination of
      analyte ions and the results were in good agreement with the certified values.
      The separation procedure presented was also applied to the various natural water
      samples collected from Turkey with satisfactory results.

PMID- 19765894
TI  - Preconcentration-separation of Co2+, Ni2+, Cu2+ and Cd2+ in real samples by solid
      phase extraction of a calix[4] resorcinarene modified Amberlite XAD-16 resin.
AB  - A new method is described for the simultaneous preconcentration of trace metal
      ions. The method is based on the adsorption of Co(2+), Ni(2+), Cu(2+) and Cd(2+)
      ions on 2,4,6,8-tetra(2-hydroxyphenyl)-1,3,5,7(1,3)tetrabenzenzcyclooctaphane
      14,16,34,36,54, 56,74,76-octol (salicylaldehyde calix[4] resorcinarenes) (new
      resorcinarenes derivative) modified on Amberlite XAD-16. The adsorbed analyte
      ions were eluted with 6 mL 3M HCl in acetone solution, which then were determined
      by atomic absorption spectroscopy. The influences of the analytical parameters
      including pH, ligand amount and solid phase ingredient, eluting solution
      conditions and sample volume were investigated. Common coexisting ions did not
      interfere with the separation and determination. The preconcentration factor is
      208. The sorbent exhibited excellent stability and its sorption capacity under
      optimum conditions has been found to be more than 60 microg of ions per gram of
      sorbent. The relative standard deviation under optimum conditions is lower than
      4.10%. The accuracy of the method was estimated by using different real samples.

PMID- 19765895
TI  - Removal of Congo Red from aqueous solution by cattail root.
AB  - In this study, cattail root was used to remove Congo Red (CR) from aqueous
      solution. The effects of operation variables, such as cattail root dosage,
      contact time, initial pH, ionic strength and temperature on the removal of CR
      were investigated using batch adsorption technique. Removal efficiency increased
      with increase of cattail root dosage and ionic strength, but decreased with
      increase of temperature. The equilibrium data fitted well to the Langmuir model
      (R(2)>0.98) and the adsorption kinetic followed the pseudo-second-order equation
      (R(2)>0.99). Thermodynamics parameters such as standard free energy change (Delta
      G degrees), standard enthalpy change (Delta H degrees), and standard entropy
      change (DeltaS degrees ) were analyzed. The values of Delta G degrees were
      between -7.871 and -4.702 kJ mol(-1), of Delta H degrees was -54.116 kJ mol(-1),
      and of DeltaS degrees was -0.157 kJ mol(-1)K(-1), revealing that the removal of
      CR from aqueous solution by cattail root was a spontaneous and exothermic
      adsorption process. The maximum adsorption capacities of CR on cattail root were
      38.79, 34.59 and 30.61 mg g(-1) at 20, 30 and 40 degrees C, respectively. These
      results suggest that cattail root is a potential low-cost adsorbent for the dye
      removal from industrial wastewater.

PMID- 19765896
TI  - Removal of Pb(II) ions from aqueous solution by adsorption using bael leaves
      (Aegle marmelos).
AB  - Biosorption of Pb(II) on bael leaves (Aegle marmelos) was investigated for the
      removal of Pb(II) from aqueous solution using different doses of adsorbent,
      initial pH, and contact time. The maximum Pb loading capacity of the bael leaves
      was 104 mg g(-1) at 50 mg L(-1) initial Pb(II) concentration at pH 5.1. SEM and
      FT-IR studies indicated that the adsorption of Pb(II) occurs inside the wall of
      the hollow tubes present in the bael leaves and carboxylic acid, thioester and
      sulphonamide groups are involved in the process. The sorption process was best
      described by pseudo second order kinetics. Among Freundlich and Langmuir
      isotherms, the latter had a better fit with the experimental data. The activation
      energy E(a) confirmed that the nature of adsorption was physisorption. Bael
      leaves can selectively remove Pb(II) in the presence of other metal ions. This
      was demonstrated by removing Pb from the effluent of exhausted batteries.

PMID- 19765897
TI  - Assessment of polycyclic aromatic hydrocarbons (PAHs) in soil of a Natural
      Reserve (Isola delle Femmine) (Italy) located in front of a plant for the
      production of cement.
AB  - Isola delle Femmine Natural Reserve is a very little isle about 15 km from the
      centre of Palermo, in front of a plant for the production of cement and about 600
      m from coast. In the present research, profiles soil PAHs were obtained for 16
      sites within the reserve and for 8 stations on the rural soil taken as reference.
      summation Sigma PAHs, in the soil of investigated area, ranged from 35 to 545
      microg/kg. With the aim to find the origin of PAHs in the soil of Isola delle
      Femmine, we compare the distribution of single analytes in the investigated area
      with those of the reference rural area (Monte Raffo Rosso), with those of
      atmospheric urban particulate collected at Palermo along with reported of
      emissions of some cement plants. The island's investigated area showed a high
      amount of 4- and 5-rings PAHs, whereas 3-ring PAHs are present mainly in the
      emission of cement plants (from literature). The percentage of 3-, 4-, 5- and 6
      rings PAHs determined in samples of Isola delle Femmine are similar to those of
      the reference rural soils and to those of urban atmospheric particulate. Cement
      plant activity has a negligible weight on the presence of PAHs in the soil of
      Isola delle Femmine.

PMID- 19765898
TI  - Impact of pyrolysis process on the chromium behavior of COPR.
AB  - The effect of pyrolysis process with sewage sludge on the chromium behavior of
      chromite ore processing residue (COPR) was examined in this study. The behavior
      of chromium was characterized in term of chromium oxidation test, pH-static
      leaching tests, column leaching test and sequential extraction test. As a
      sequence of pyrolysis process, the Cr(VI) in COPR was effectively reduced from
      5057 mg kg(-1) for untreated COPR to 8.6 mg kg(-1) for treated COPR at
      temperature over 600 degrees C, which is far below the New Jersey Department of
      Environmental Protection regulatory limit of 240 mg kg(-1). As a result, the
      amount of exchangeable and carbonate-bound Cr fractions, the most mobile for the
      environment, were largely reduced. At the same time, the amount of the other
      three Cr fractions which are much less mobile become augmented. pH static test
      showed that the chromium in the treated COPR at pyrolysis temperature above 400
      degrees C was quite stable at pH>7. Column study also indicated that only
      negligible amount of chromium of the treated COPR at above 600 degrees C can be
      released by the acid rain.

PMID- 19765899
TI  - Effect of preparation conditions of activated carbon from bamboo waste for real
      textile wastewater.
AB  - This study deals with the use of activated carbon prepared from bamboo waste
      (BMAC), as an adsorbent for the removal of chemical oxygen demand (COD) and color
      of cotton textile mill wastewater. Bamboo waste was used to prepare activated
      carbon by chemical activation using phosphoric acid (H(3)PO(4)) as chemical
      agent. The effects of three preparation variables activation temperature,
      activation time and H(3)PO(4):precursor (wt%) impregnation ratio on the color and
      COD removal were investigated. Based on the central composite design (CCD) and
      quadratic models were developed to correlate the preparation variables to the
      color and COD. From the analysis of variance (ANOVA), the most influential factor
      on each experimental design response was identified. The optimum condition was
      obtained by using temperature of 556 degrees C, activation time of 2.33 h and
      chemical impregnation ratio of 5.24, which resulted in 93.08% of color and 73.98%
      of COD.

PMID- 19765900
TI  - Air detoxification with nanosize TiO2 aerosol tested on mice.
AB  - A method for fast air purification using high concentration aerosol of TiO(2)
      nanoparticles is evaluated in a model chemical catastrophe involving toxic vapors
      of diisopropyl fluorophosphate (DFP). Mice are used as human model in a closed
      100 dm(3) chamber. Exposure of mice to 37 ppm of DFP vapor for 15 min resulted in
      acute poisoning. Spraying TiO(2) aerosol in 2 min after the start of exposure to
      DFP vapors resulted in quick removal of DFP vapors from the chamber's air.
      Animals did not show signs of poisoning after the decontamination experiment and
      exposure to TiO(2) aerosol alone. Reactive oxygen species (ROS) and antioxidant
      activity (AOA) of mice blood plasma were measured for animals exposed to sound of
      aerosol generator, DFP vapors, TiO(2) aerosol and DFP vapors+TiO(2) aerosol.
      Reduced ROS and increased AOA were found for mice exposure to sound, DFP and
      TiO(2) aerosol. Exposure to DFP and decontamination with TiO(2) nanoparticles
      resulted in decreased AOA in 48 h following the exposure. The results suggest
      that application of TiO(2) aerosol is a powerful method of air purification from
      toxic hydrolysable compounds with moderate health aftermaths and requires further
      study and optimization.

PMID- 19765901
TI  - Removal of heavy metals from wastewater using CFB-coal fly ash zeolitic
      materials.
AB  - Polish bituminous (PB) and South African (SA) coal fly ash (FA) samples, derived
      from pilot-scale circulated fluidized bed (CFB) combustion facilities, were
      utilized as raw materials for the synthesis of zeolitic products. The two FAs
      underwent a hydrothermal activation with 1M NaOH solution. Two different FA/NaOH
      solution/ratios (50, 100g/L) were applied for each sample and several zeolitic
      materials were formed. The experimental products were characterized by means of X
      ray diffraction (XRD) and energy dispersive X-ray coupled-scanning electron
      microscope (EDX/SEM), while X-ray fluorescence (XRF) was applied for the
      determination of their chemical composition. The zeolitic products were also
      evaluated in terms of their cation exchange capacity (CEC), specific surface area
      (SSA), specific gravity (SG), particle size distribution (PSD), pH and the range
      of their micro- and macroporosity. Afterwards the hybrid materials were tested
      for their ability of adsorbing Cr, Pb, Ni, Cu, Cd and Zn from contaminated
      liquids. Main parameters for the precipitation of the heavy metals, as it was
      concluded from the experimental results, are the mineralogical composition of the
      initial fly ashes, as well as the type and the amount of the produced zeolite and
      specifically the mechanism by which the metals ions are hold on the substrate.

PMID- 19765902
TI  - A model based atomic resolution tomographic algorithm.
AB  - Tomography with high angular annular dark field scanning transmission electron
      microscopy at atomic resolution can be greatly improved if one is able to take
      advantage of prior knowledge. In this paper we present a reconstruction technique
      that explicitly takes into account the microscope parameters and the atomic
      nature of the projected object. This results in a more accurate estimate of the
      atomic positions and in a good resistance to noise. The reconstruction is a
      maximum likelihood estimator of the object. Moreover, the limits to the precision
      have been explored, allowing for a prediction of the amount of expected noise in
      the reconstruction for a certain experimental setup. We believe that the proposed
      reconstruction technique can be generalized to other tomographic experiments.

PMID- 19765903
TI  - Babesia divergens experimental infection of spleen-intact sheep results in long
      lasting parasitemia despite a strong humoral response: preliminary results.
AB  - Babesia divergens is an intraerythrocytic Apicomplexa and the main agent of
      bovine babesiosis in Europe. The infection in cattle develops in 2 phases: an
      acute phase with hemolytic anemia and a chronic phase with asymptomatic
      persistence of the parasite for several years. The acute phase of B. divergens
      infection can be studied using the gerbil (Meriones unguiculatus) as a laboratory
      model but unlike cattle, this animal rapidly eliminates the parasite. An
      experimental model to study the chronic phase of infection was therefore
      developed by our laboratory. Spleen-intact sheep, with a potential full immune
      response, were inoculated with infected red blood cells (iRBC) or with free
      merozoites, by several routes (intraperitoneal, intravenous or subcutaneously).
      No clinical signs were ever observed but the installation of a persistent low
      level infection was shown in sheep with susceptible erythrocytes (able to sustain
      B. divergens growth in vitro). Neither feature was observed in sheep with non
      susceptible erythrocytes. IgG production, involving both IgG1 and IgG2, was
      mainly directed against the major merozoite surface antigen Bd37, similar to the
      humoral immune response described in naturally infected cattle. The use of spleen
      intact sheep to study the immune response to B. divergens is discussed.

PMID- 19765904
TI  - Avulsion fracture of the olecranon following thermal injury: a case report.

PMID- 19765905
TI  - Burn severity and post-burn infertility in men.
AB  - Burn wounds are a common cause of much morbidity and misery, especially in low-
      and medium-income countries. A number of studies show that severe burns cause
      infertility from poor sperm production. The pathways leading to such infertility
      are not well understood, and it is not known how the severity of injury affects
      this post-burn infertility (PBI). We evaluated the relationship between sperm
      parameters and indices of burn severity, such as burn surface area and depth in
      19 adults. Total sperm counts ranged from 0 to 160 million/ml, with a mean of
      19.58+/-7.52 million/ml. About 60% of the subjects had total counts of 20
      million/ml or less, falling into the clinically oligospermic range. We found only
      a weak correlation between infertility and both burn depth and burn surface area.
      There was, however, a fairly strong positive correlation between infertility and
      length of time between injury and participation in the study. The correlation
      coefficient was 0.560. Our findings suggest that PBI is progressive and not
      predicted by TBSA. Any measures to control it should be started early and be
      applied to burn patients across a wide range of clinical severity.

PMID- 19765906
TI  - Description of Streptococcus pneumoniae infections in burn patients.
AB  - BACKGROUND: Longer survival in burn patients has resulted in more infectious
      complications, typically with Klebsiella pneumoniae, Pseudomonas aeruginosa,
      Acinetobacter baumannii, and Staphylococcus aureus. Although Streptococcus
      pneumoniae infections are common in the community and can cause nosocomial
      infections, the incidence and risk factors for pneumococcal infections in burn
      patients is unclear. METHODS: We performed an electronic retrospective chart
      review to collect rates of and risk factors for S. pneumoniae infections in
      patients with thermal burns from March 2003 through June 2008. RESULTS: Of the
      1838 patients admitted to the burn center, 10 were infected (0.54% incidence).
      Patients presented with pneumonia (seven patients, 0.38% incidence) and
      bacteremia (three patients, 0.16% incidence) within a week of initial burn
      (median 1 day, range 0-8), often in the setting of bacterial co-infection (five
      patients). This group was mainly young males with median 28.8% total body surface
      area burns; 60% had concomitant inhalational injury. Most did not have
      traditional risk factors for pneumococcal infection but had objective signs of
      infection at time of positive culture and were treated with appropriate
      antibiotics. Two patients in this series died, although no mortality was
      attributed to S. pneumoniae. CONCLUSIONS: Pneumococcal disease is not common in
      burn patients and generally occurs early on in hospitalization after burn making
      it more likely to be a community-acquired pathogen rather than nosocomial in the
      burn population. It should be considered in the setting of sepsis or new
      pulmonary infiltrates within a week after burn, but typical empiric antibiotics
      against the usual burn pathogens should be adequate to also treat for
      pneumococcal infection.

PMID- 19765907
TI  - Saving the zone of stasis in burns with activated protein C: an experimental
      study in rats.
AB  - Salvage of the zone of stasis is a major subject of focus in burn research. Use
      of various antithrombotic, anti-inflammatory and antioxidant drugs have been
      studied experimentally, with reports of favourable results; however, none became
      popular in clinical practice. Activated protein C (APC) is a well-known
      physiologic anticoagulant. Recent studies revealed that APC contributes not only
      to systemic anticoagulant activities but also to anti-inflammatory activities by
      inhibiting leucocyte activation associated with TNF production. The likely
      favourable effects of APC on salvage of the zone of stasis were investigated on a
      well-described experimental rat burn model representing the zone of stasis
      according to the 'burn comb model'. Twenty Sprague-Dawley rats were used and
      randomly separated into experimental and control groups. Two hours after inducing
      injury, 100 microg kg(-1) APC (Sigma, Boehringer Ingelheim, Germany) was
      administered to the experimental group through the caudal vein while 0.9% saline
      was injected through the same route in the control group. Laser Doppler flowmetry
      measurements and autoradiography were used for evaluation of perfusion and
      viability in the zone of stasis. At day 3, the differences between the results
      obtained from the treatment and the control groups were found to be statistically
      significant (p<0.05). Our experimental study revealed that APC improved tissue
      perfusion and decreased the area of skin necrosis in the zone of stasis in rats.
      The dual effect of APC, each of which has been shown to be favourable in saving
      the zone of stasis, may make this agent effective with a single effect in
      treatment of burn injury.

PMID- 19765908
TI  - Migraine, neuropathic pain and nociceptive pain: towards a unifying concept.
AB  - Migraine, neuropathic pain and nociceptive pain are the three commonest pain
      syndromes affecting human. In the present article, we first present the salient
      features of the pathophysiology of the three conditions particularly highlighting
      the core features that are similar in the three conditions. We argue on the
      validity of the prevailing concept that maintenance of structural integrity of
      the nervous system differentiates nociceptive pain from neuropathic pain and
      point out that the fundamental pathophysiology of lasting nociceptive pain (like
      cancer pain) and neuropathic pain (like nerve injury pain) is essentially same.
      Migraine pathophysiology is complex and complicated by two opposing views on site
      of migraine pain generation - peripheral versus central. We hypothesize that this
      dichotomy has resulted from focusing on two different sites on a single, somewhat
      complicated, pain mediating circuitry from the peripheral meningeal and vascular
      structures through several cell stations in the brain stem and thalamus up to the
      sensory cortical matrix. At the end, we suggest that fundamentally all the three
      pain syndromes referred to in the article share a common pathophysiological
      mechanism, namely peripheral pain perception, peripheral sensitization at dorsal
      root ganglion or its intracranial counterpart (like trigeminal ganglion) and
      central sensitization at the spinal cord (dorsal horn for somatic pain), brain
      stem nuclei and thalamus before final pain perception at the sensory cortical
      matrix.

PMID- 19765909
TI  - Large prospective birth cohort studies on environmental contaminants and child
      health - goals, challenges, limitations and needs.
AB  - The adverse health effects of environmental contaminants (ECs) are a rising
      public health concern, and a major threat to sustainable socioeconomic
      development. The developing fetuses and growing children are particularly
      vulnerable to the adverse effects of ECs. However, assessing the health impact of
      ECs presents a major challenge, given that multiple outcomes may arise from one
      exposure, multiple exposures may result in one outcome, and the complex
      interactions between ECs, and between ECs, nutrients and genetic factors, and the
      dynamic temporal changes in EC exposures during the life course. Large-scale
      prospective birth cohort studies collecting extensive data and specimen starting
      from the prenatal or pre-conception period, although costly, hold promise as a
      means to more clearly quantify the health effects of ECs, and to unravel the
      complex interactions between ECs, nutrients and genotypes. A number of such large
      scale studies have been launched in some developed counties. We present an
      overview of "why", "what" and "how" behind these efforts with an objective to
      uncover major unidentified limitations and needs. Three major limitations were
      identified: (1) limited data and bio-specimens regarding early life EC exposure
      assessments in some birth cohort studies; (2) heavy participant burdens in some
      birth cohort studies may bias participant recruitment, and risk substantial loss
      to follow-up, protocol deviations limiting the quality of data and specimens
      collection, with an overall potential bias towards the null effect; (3) lack of
      concerted efforts in building comparable birth cohorts across countries to take
      advantage of natural "experiments" (large EC exposure level differences between
      countries) for more in-depth assessments of dose-response relationships,
      threshold exposure levels, and positive and negative effect modifiers. Addressing
      these concerns in current or future large-scale birth cohort studies may help to
      produce better evidence on the health effects of ECs.

PMID- 19765910
TI  - A possible explanation of the germicide effect of carbon dioxide in supercritical
      state based on molecular-biological evidence.
AB  - Supercritical carbon dioxide (CO(2)) possesses germicide (bactericide and
      sporicide) effect. Despite of the fact, that this effect is used in industrial
      sterilization processes, the sterilization mechanism at molecular level is
      unclear. Our hypotheses can provide a molecular-biological explanation for the
      phenomenon. We believe that in supercritical state CO(2) reacts competitively
      with Met-tRNA(fMet), the formation rate and the amount of formyl-methionyl-tRNA
      (fMet-tRNA(fMet)) will be diminished by irreversible substrate consumption. The
      fMet-tRNA(fMet) possesses a key role in prokaryotic protein synthesis, being
      almost exclusively the initiator aminoacyl-tRNA. The formed carbamoyl-methionyl
      tRNA (cMet-tRNA(fMet)), probably stable only under pressure and high CO(2)
      concentration, is stabilized by forming a ternary molecular complex with the GTP
      form of the translational initiation factor 2 (GTP-IF2). This complex is unable
      to dissociate from preinitiation 70S ribosomal complex because of strong polar
      binding between the protein C-2 domain and the modified initiator aminoacyl-tRNA.
      The IF2-fMet-tRNA(fMet)-blocked 70S ribosomal preinitiation complex does not
      decompose following the GTP hydrolysis, becoming unable to synthesize proteins.
      The death of the microbial cell is caused by inhibition of the protein synthesis
      and energetic depletion. Moreover, we propose a possible mechanism for the
      accumulation of cMet-tRNA(fMet) in the bacterial cell. Since the translational
      process is an important target for antibiotics, the proposed mechanism could be a
      work hypothesis for discovery of new antibiotics. Made by high conservative
      character of prokaryotic translation initiation, the proposed IF2 pathway
      deterioration strategy may conduct to obtaining selective (with low mammalian
      toxicity) antimicrobials and at the same time, with reduced possibility of the
      drug resistance development.

PMID- 19765911
TI  - Wisdom teeth: mankind's future third vice-teeth?
AB  - The third molar teeth (wisdom teeth) represent the last eruption of the teeth in
      the human dentition. Throughout evolution, the mandible has had a tendency to
      decrease in size; the third molar teeth are often impacted, resulting in
      incomplete tooth eruption that often causes clinical pericoronitis, dental
      caries, and pericemental abscess. Therefore, the wisdom teeth are often
      extracted. Moreover, wisdom teeth are often removed for clinical orthodontic
      treatment. On the other hand, tooth loss due to periodontal disease, dental
      caries, trauma, or a variety of genetic disorders continues to affect people's
      lives. Autologous tissues for dental tissue regeneration that could replace lost
      teeth could provide a vital alternative to currently available clinical
      treatments. To pursue this goal, we hypothesize that human third molar tooth buds
      can be obtained during development. Human wisdom tooth germination tissue could
      then be placed into an embryonic stem cell bank for storage. When the donor's
      other teeth are missing, embryonic stem cell and tissue engineering technologies,
      will permit the restoration of the missing teeth. Therefore wisdom teeth will be
      mankind's future third vice-teeth.

PMID- 19765912
TI  - Colchicine treatment in autosomal dominant polycystic kidney disease: many points
      in common.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is the most common of the
      inherited renal cystic diseases and constitutes 10% of the end stage kidney
      disease population. ADPKD is caused by PKD1 and PKD2 gene mutations in 85% and
      15% of the cases respectively. Its high prevalence and negative impact on health
      outcomes fostered efforts to explain pathophysiologic pathways of cyst formation
      in kidneys. Among these are increased apoptosis, unopposed proliferation of
      tubule cells, impaired polarization and planar cell polarity, impaired cAMP
      pathway, cilier dysfunction, activated mTOR pathway, increased tumor necrosis
      factor-alpha (TNF-alpha) production. Many drugs have been tried in an attempt to
      halt cystogenesis in some point. Despite success to some extent in experimental
      studies, none reached clinical armamentarium yet. Colchicine, originally
      extracted from Colchicum autunale, is an anti-inflammatory drug that has been in
      continuous use for more than 3000 years. It has been used successfully to prevent
      attacks of familial mediterranien fever and amyloidosis, to treat gout and
      pseudogout attacks for a few decades. Colchicine principally is a microtubule
      inhibitor, thus prevents cell migration, division, and polarization. It also has
      anti-apoptotic, anti-proliferative and anti-inflammatory effects and down
      regulates (TNF-alpha) receptors. As can easily be seen, many of the effects of
      colchicine have pathophysiologic counterparts in ADPKD. Thus, we hypothesized
      that colchicine would be beneficial to prevent or at least delay cyst formation
      in ADPKD patients. Indirect evidence also support our hypothesis, in which taxol
      and paclitaxel, other two microtubule inhibitors, were shown to delay cyst
      formation in experimental models of ADPKD. To our opinion, despite its narrow
      therapeutic index, widespread experience makes colchicine a suitable candidate
      for prolonged clinical use, should experimental studies show any benefit in
      ADPKD.

PMID- 19765913
TI  - Intensity-modulated radiotherapy-based stereotactic body radiotherapy for
      medically inoperable early-stage lung cancer: excellent local control.
AB  - PURPOSE: To validate the use of stereotactic body radiotherapy (SBRT) using
      intensity-modulated radiotherapy (IMRT) beams for medically inoperable Stage I
      lung cancer. METHODS AND MATERIALS: From February 2004 to November 2006, a total
      of 26 patients with 28 lesions received SBRT using a Novalis/BrainLAB system.
      Immobilization involved a Bodyfix vacuum cushion. A weighted abdominal belt
      limited respiratory excursion. Computed tomographic simulation images were
      acquired at rest, full inhalation, and full exhalation and were merged to
      generate an internal gross tumor volume (ITV). Dose was prescribed to cover the
      planning target volume (PTV), defined as PTV = ITV + 3-5 mm set-up margin.
      Heterogeneity corrections were used. Delivery of 50 Gy in five sequential
      fractions typically used seven nonopposing, noncoplanar beams. Image-guided
      target verification was provided by BrainLAB-ExacTrac. RESULTS: Among the 26
      patients, the mean age was 74 years (range, 49-88 years). Of the patients, 50%
      were male and 50% female. The median Karnofsky performance status was 70 (range,
      40-100). The median follow-up was 30.9 months (range, 10.4-51.4 months). Tissue
      diagnosis was contraindicated in seven patients (26.9%). There were 22 T1 (78.6%)
      and six T2 (21.4%) tumors. The median conformality index was 1.38 (range, 1.12
      1.8). The median heterogeneity index was 1.08 (range, 1.04-1.2). One patient
      (3.6%) developed acute Grade 3 dyspnea and one patient developed late Grade 2
      chest wall pain. Actuarial local control and overall survival at 3 years were
      94.4% and 52%, respectively. CONCLUSIONS: Use of IMRT-based delivery of SBRT
      using restriction of tumor motion in medically inoperable lung cancer
      demonstrates excellent local control and favorable survival.

PMID- 19765914
TI  - Spinal cord tolerance for stereotactic body radiotherapy.
AB  - PURPOSE: Dosimetric data are reported for five cases of radiation-induced
      myelopathy after stereotactic body radiotherapy (SBRT) to spinal tumors. Analysis
      per the biologically effective dose (BED) model was performed. METHODS AND
      MATERIALS: Five patients with radiation myelopathy were compared to a subset of
      19 patients with no radiation myelopathy post-SBRT. In all patients, the thecal
      sac was contoured to represent the spinal cord, and doses to the maximum point,
      0.1-, 1-, 2-, and 5-cc volumes, were analyzed. The mean normalized 2-Gy
      equivalent BEDs (nBEDs), calculated using an alpha/beta value of 2 for late
      toxicity with units Gy 2/2, were compared using the t test and analysis of
      variance test. RESULTS: Radiation myelopathy was observed at the maximum point
      with doses of 25.6 Gy in two fractions, 30.9 Gy in three fractions, and 14.8,
      13.1, and 10.6 Gy in one fraction. Overall, there was a significant interaction
      between patient subsets and volume based on the nBED (p = 0.0003). Given
      individual volumes, a significant difference was observed for the mean maximum
      point nBED (p = 0.01). CONCLUSIONS: The maximum point dose should be respected
      for spine SBRT. For single-fraction SBRT 10 Gy to a maximum point is safe, and up
      to five fractions an nBED of 30 to 35 Gy 2/2 to the thecal sac also poses a low
      risk of radiation myelopathy.

PMID- 19765915
TI  - [Conceptual framework for integrating reproductive health in school: experience
      in Senegal].
AB  - OBJECTIVE: Adolescent reproductive health is a public health concern. The
      objective of this article is to report the conceptual framework for integrating
      reproductive health services in school from a pilot project carried out in
      Senegal. MATERIALS AND METHODS: A 10-year strategic plan from 2000 to 2010 for
      education and training has been established by the Ministry of Education and the
      component related to health and nutrition has been in charge by the medical
      health control division (DCMS). By putting into action the strategy of this
      component, a pilot project for integrating reproductive health in school had been
      set up and carried out from 2002 to 2006. This project was held within a
      secondary grade school and in a health structure especially designated for
      students. RESULTS: School health policy established by the Ministry of Education
      and the choice of the DCMS as the institutional leadership has helped to define a
      framework for synergic interventions directed to school-aged children. Thus, the
      coordination team with health experts has carried out the project held through a
      participatory process and advocacy since its conception phase putting together
      the authority of the Ministry, the school-aged children, the teachers and the
      parents. Capacities strengthening of different stakeholders through training,
      sensibilisation and information have been made with partnership development and a
      signed protocol between the Ministry of Education and the Ministry of Health.
      CONCLUSION: The magnitude of adolescent reproductive health problems justifies
      the integration of reproductive health services in school.

PMID- 19765916
TI  - Nicotine dependence symptoms among recent onset adolescent smokers.
AB  - The present study examined the prevalence of individual nicotine dependence
      symptoms among recent onset smokers across the continuum of nondaily and daily
      cigarette smoking behavior in a nationally representative sample of recent onset
      smokers from the National Surveys on Drug Use and Health (NSDUH). Rates of
      endorsement for 17 symptoms drawn primarily from the Nicotine Dependence Symptom
      Scale (Shiffman et al., 2004) were calculated for four levels of nondaily (smoked
      1-3, 4-10, 11-20, or 21-29 days in the past 30 days) and daily (smoked 1, 2-5, 6
      15, or >15 cigarettes per day in the past 30 days) smoking. Logistic and linear
      regression analyses with polynomial contrasts controlling for age, gender, length
      of exposure, and smoking quantity tested trends in symptom endorsement across
      levels of smoking. Significant linear and quadratic trends indicated that
      increasing rates of endorsement differed most between the lowest levels of
      nondaily and daily smoking. Results suggest that, for some, infrequent smoking
      may not represent benign experimentation. Recognizing early symptoms of nicotine
      dependence may assist in early identification and intervention of those at risk
      for heavier smoking in the future. Adolescents can be taught to recognize the
      early symptoms of nicotine dependence to increase awareness of the rapidity at
      which these symptoms may appear.

PMID- 19765917
TI  - Zoonotic tick-borne flaviviruses.
AB  - Tick-borne flaviviruses are among the medically most important arboviruses in
      Europe and Asia. Tick-borne encephalitis causes between 10,000 and 15,000 human
      cases every year in both continents. Besides this disease there are several other
      tick-borne flaviviruses which may be of local medical importance, and which are
      less known, but may be important as differential diagnosis. Among them are
      louping-ill disease which is present mainly on the British Islands, Omsk
      hemorrhagic fever, which is prevalent in parts of Russia, Kyasanur Forest
      Disease, which is distributed in parts of India, Alkhumra hemorrhagic fever,
      occurring in Saudi Arabia, Powassan encephalitis, which is known to be the only
      tick-borne flavivirus of human pathogenicity so far detected in North America and
      some other flaviviruses. Most of these viruses are also more or less important
      for veterinary medicine. Several other tick-borne flaviviruses so far have
      neither been associated with human nor animal diseases, and their potential
      pathogenicity for humans and animals is unknown. Changes in human behaviour, land
      use, or climate may change the actual geographical distribution and transmission
      intensity so that tick-borne flaviviruses are potential winners of the changing
      environment and may increase in medical and veterinary importance.

PMID- 19765919
TI  - Neonates born from mothers with autoimmune disorders.
AB  - Systemic autoimmune disorders have a higher prevalence in women, particularly
      during their childbearing age. A growing interest is being paid to the possible
      consequences of maternal disease and associated treatment on the fetus and
      newborn infant. If maternal disease is characterized by the presence of IgG
      isotype auto-antibodies, these can cross the placenta with possible antibody
      mediated damage to the fetus. The risk of gestational complications, including
      preterm delivery, intrauterine growth retardation and low birth weight is higher
      in autoimmune diseases rather than in the general population and probably this
      finding is related to both maternal disorder and immunosuppressive therapy.
      Recently, results of our studies suggest that the antenatal exposure to
      immunosuppressive drugs given to mothers during pregnancy to treat autoimmune
      diseases does not impair significantly the development of immunity in exposed
      children. Finally, mothers disease and/or treatment could be related to
      neuropsychological dysfunctions reported in some of their children.

PMID- 19765918
TI  - The ELGAN study of the brain and related disorders in extremely low gestational
      age newborns.
AB  - BACKGROUND: Extremely low gestational age newborns (ELGANs) are at increased risk
      for structural and functional brain abnormalities. AIM: To identify factors that
      contribute to brain damage in ELGANs. STUDY DESIGN: Multi-center cohort study.
      SUBJECTS: We enrolled 1506 ELGANs born before 28 weeks gestation at 14 sites;
      1201 (80%) survived to 2 years corrected age. Information about exposures and
      characteristics was collected by maternal interview, from chart review,
      microbiologic and histological examination of placentas, and measurement of
      proteins in umbilical cord and early postnatal blood spots. OUTCOME MEASURES:
      Indicators of white matter damage, i.e. ventriculomegaly and echolucent lesions,
      on protocol cranial ultrasound scans; head circumference and developmental
      outcomes at 24 months adjusted age, i.e., cerebral palsy, mental and motor scales
      of the Bayley Scales of Infant Development, and a screen for autism spectrum
      disorders. RESULTS: ELGAN Study publications thus far provide evidence that the
      following are associated with ultrasongraphically detected white matter damage,
      cerebral palsy, or both: preterm delivery attributed to preterm labor, prelabor
      premature rupture of membranes, or cervical insufficiency; recovery of
      microorganisms in the placenta parenchyma, including species categorized as human
      skin microflora; histological evidence of placental inflammation; lower
      gestational age at delivery; greater neonatal illness severity; severe chronic
      lung disease; neonatal bacteremia; and necrotizing enterocolitis. CONCLUSIONS: In
      addition to supporting a potential role for many previously identified
      antecedents of brain damage in ELGANs, our study is the first to provide strong
      evidence that brain damage in extremely preterm infants is associated with
      microorganisms in placenta parenchyma.

PMID- 19765920
TI  - Probability of pregnancy as affected by oestrus number and days to first oestrus
      in dairy cows of three breeds and parities.
AB  - An improved understanding of the animal factors that affect measures such as
      conception rate would contribute to solving the problem of impaired reproductive
      performance in modern dairy cows. A question of particular interest relates to
      the observed improvement in conception rates from first to second and third
      oestrus cycle: is the increase in conception rate related to cycle number per se
      or to increasing days from calving? A 5-year study using three breeds (Holstein,
      Jersey and Danish Red) allowed this issue to be examined. In 560 lactations, from
      calving until confirmed pregnancy or until 290 days after calving all cows were
      observed daily for signs of oestrus. Inseminations were carried out to all clear
      cases of oestrus after 35 days from calving until the cow was judged to be
      pregnant or until 290 days post-calving. Days from calving to the first oestrus
      was modeled using a frailty model. Danish Red cows had a significantly greater
      rate of occurrence of first oestrus over time. Generalized linear mixed models
      defined using a binomial distribution and logit link function were used to
      estimate probability of pregnancy as affected by: breed, parity, oestrus number
      and days from calving to first oestrus. In order to account for the paradox that
      the incidence of cows with inherently low fertility increases with oestrus
      number, different random components for cow were included. There was a
      significant increase in probability of pregnancy from first to second oestrus but
      no significant change in probability of pregnancy thereafter. There was a
      significant increase in probability of pregnancy with increasing days to first
      oestrus. This indicates that both oestrus number and days from calving play a
      role in determining the fertility of dairy cows. Correcting for inherent
      differences in fertility was shown to be important.

PMID- 19765921
TI  - Birth of offspring after artificial insemination of heifers with frozen-thawed,
      sex-sorted, re-frozen-thawed bull sperm.
AB  - Two field trials were conducted to determine the fertilising capacity of (i)
      frozen-thawed, sex-sorted re-frozen-thawed (FSF) dairy bull sperm inseminated
      close to the time of ovulation, (ii) FSF sperm following large dose insemination,
      and frozen-thawed, sex-sorted (FS) sperm inseminated within 12h after sorting. In
      Trial 1, 24 heifers in synchronised oestrus were observed for standing heat over
      a 30-min period once every 3h. Upon observation of standing heat, the size of the
      pre-ovulatory follicle was tracked by ultrasound every 6h until ovulation was
      judged to be imminent. Heifers were inseminated with 4 x 10(6) X-bearing FSF or
      Control sperm within 6h of ovulation. Ovaries were scanned 6h after AI to ensure
      ovulation had occurred. All 24 heifers displayed standing oestrus and 20 of these
      subsequently ovulated. The mean length of standing oestrus was 16.8+/-0.4h and
      ovulation occurred 27.6+/-1.1h after the onset of standing heat from a pre
      ovulatory follicle with a diameter of 16.1+/-0.3mm. All 12 heifers that received
      FSF sperm returned to oestrus<26d after AI. Of 8 heifers that received Control
      sperm, 6 (75%) were confirmed pregnant by ultrasound 7 wk after AI, confirming
      that the method of AI and herd fertility were sound. In Trial 2 the number of
      sperm inseminated and the effect of eliminating the post-sort cryopreservation
      step were investigated. Heifers (n=21) were synchronised for oestrus, and
      inseminated 24h after the onset of standing oestrus with 10 x 10(6) X-bearing
      FSF, 4 x 10(6) X-bearing FS, or 10 x 10(6) non-sorted frozen-thawed (Control)
      sperm. Heifers were observed for return to oestrus from 21d, and diagnosed for
      pregnancy 7 wk after AI. Of the 7 heifers that received FSF sperm, one was
      confirmed pregnant (14.3%) and delivered a female calf. Four heifers inseminated
      with control sperm became pregnant and calved, but no pregnancies were obtained
      using FS sperm. The birth of a calf following AI with FSF sperm demonstrates the
      potential of sorting from frozen-thawed semen, and with further work, may be a
      promising technique that will give producers access to sexed sperm from a greater
      range of bulls.

PMID- 19765922
TI  - Matrix metalloproteinases-1, -2 expression in uterosacral ligaments from women
      with pelvic organ prolapse.
AB  - OBJECTIVE: This study investigated matrix metalloproteinase-1 (MMP-1) and matrix
      metalloproteinase-2 (MMP-2) immunohistochemical expression in uterosacral
      ligament biopsies from women with pelvic organ prolapse (POP), and controls with
      normal pelvic support. DESIGN: Prospective observational experimental study.
      SETTING: A tertiary Urogynecology Unit and Institute of Pathology, University
      Hospital Split, Croatia. POPULATION: Women referred for hysterectomy for prolapse
      or benign gynecological disease. METHODS: Eighty postmenopausal women were
      included in the study after Ethical Committee approval and informed consent.
      During surgery, uterosacral ligament biopsies were obtained from patients with
      POP (n=40) and women without evidence of pelvic floor weakening (n=40).
      Immunohistochemistry for MMP-1 and MMP-2 was performed on formaline fixed and
      paraffin embedded sections. Statistical evaluations were made by Student t-test
      or chi(2) test. MAIN OUTCOME MEASURES: Immunohistochemical expression of MMP-1
      and MMP-2 in the uterosacral ligaments of women with and without genital
      prolapse. RESULTS: Forty women with POP and 40 controls without POP were
      included. The controls were matched to the women with POP in age, body mass
      index, parity and duration of postmenopausis. A significant increase in MMP-1
      immunohistochemical expression was seen in uterosacral ligament tissue from women
      with POP (P=0.029). In contrast, there was no difference in immunohistochemical
      expression of MMP-2 between women with POP and those without (P=0.899).
      CONCLUSION: These data suggest that MMP-1 may be marker of collagen degradation.
      Increased MMP-1 immunohistochemical expression in uterosacral ligaments is
      associated with urogenital prolapse.

PMID- 19765923
TI  - A study for establishing the sequence of superimposed lines: inkjet versus
      writing instruments.
AB  - Intersections of inkjet strokes of different color (black, red, green and blue)
      with ballpoint ink or gel pen ink or fountain pen ink strokes each of different
      color (black, red, green and blue) were examined under stereomicroscope and
      digital microscope. The exemplars (25,920 intersections) were prepared on three
      types of paper at three time intervals. Stereomicroscope proves very successful
      in determining the sequence of ballpoint ink or gel pen ink of different color
      and inkjet stroke of black color only. It also helps in determining the sequence
      of intersections of fountain ink strokes (all color) and inkjet strokes (all
      color) with highest success rate (100% correctness). The digital microscope is
      not useful in determining the order of inkjet strokes and ballpoint ink or gel
      pen ink. These observations show that for the correct order of sequence,
      intersections magnification as well as good angle of illumination is required.

PMID- 19765924
TI  - Basic forensic identification of artificial leather for hit-and-run cases.
AB  - Single fibers retrieved from a victim's garments and adhered to the suspect's
      automobile have frequently been used to prove the relationship between victim and
      suspect's automobile. Identification method for single fiber discrimination has
      already been conducted. But, a case was encountered requiring discrimination of
      artificial leather fragments retrieved from the victim's bag and fused fibers
      from the bumper of the suspect's automobile. In this report, basic studies were
      conducted on identification of artificial leathers and single fibers from leather
      materials. Fiber morphology was observed using scanning electron microscopy
      (SEM), color of these leather sheets was evaluated by microspectrophotometry
      (MSP), the leather components were measured by infrared micro spectrometry (micro
      FT-IR) and the inorganic contents were ascertained by micro-X-ray fluorescence
      spectrometry (micro-XRF). These two methods contribute to other analytical
      methods too, in the case of utilized single fiber analytical methods. The
      combination of these techniques showed high potential of discrimination ability
      in forensic examinations of these artificial leather samples. In regard with
      smooth surface artificial leather sheet samples, a total of 182 sheets were
      obtained, including 177 colored sheets directly from 10 of 24 manufacturers in
      Japan, and five of them were purchased at retail circulation products. Nine
      samples of suede-like artificial leather were obtained, 6 of them were supplied
      from 2 manufacturers and 3 sheets were purchased as retailing product. Single
      fibers from the smooth surface artificial leather sheets showed characteristic
      for surface markings, and XRF could effectively discriminate between these
      sheets. The combination of results of micro-FT-IR, color evaluation by MSP and
      the contained inorganic elements by XRF enabled to discriminate about 92% of
      15,576 pairs comparison. Five smooth surface samples form retailing products were
      discriminated by their chemical composition into four categories, and in addition
      color information to this result, they were clearly distinguished. Suede-like
      artificial leather sheets showed characteristic extra-fine fibers on their
      surface by the observation of SEM imaging, providing high discriminating ability,
      in regard with suede-like artificial leather sheets were divided into three
      categories by micro-FT-IR, and the combination of these results and color
      evaluation information, it was possible to discriminate all the nine suede-like
      artificial leather sheets examined.

PMID- 19765925
TI  - A case of shotgun injury which occurred while an unconventional home security
      alarm system was being checked.
AB  - Installation of devices involving shotguns is rarely encountered in forensic
      medicine practice. In this case report, authors aimed to present an unusual and
      rare case of shotgun injury due to a home security alarm system and its legal
      assessment. An electrical technician was invited to a summer house to check a
      home security alarm system installed by another firm which he worked for
      previously. It was an unconventional home security alarm system attached to a
      shotgun. The technician was injured with 18 buckshot pellets (no: 4) while
      checking the system. The host was convicted of a possible intent to cause a life
      threatening injury to the technician. We think that this verdict will set a
      precedent for similar cases.

PMID- 19765926
TI  - Bilateral brachial plexus palsy and right Horner syndrome due to congenital
      cervicothoracal syringomyelia.
AB  - Syringomyelia (SM) is a disorder in which a cyst forms within the spinal cord.
      This cyst, called a syrinx, expands and elongates over time, destroying the
      center of the cord. Horner syndrome is an infrequent illness caused by a lesion
      of the cervical sympathetic nerve fiber. Its clinical features are facial
      anhidrosis, ptosis, miosis, and hypochromia iridis of the affected side. A full
      term male newborn infant was admitted with weakness in bilateral upper
      extremities and narrowing of the palpebral fissure on the right side.
      Ophthalmologic examination revealed a smaller right pupil. Muscle power in
      bilateral upper limbs was 1/5. Chest X-ray and cranial magnetic resonance imaging
      were normal. Magnetic resonance imaging of the cervicothoracic spine showed SM at
      C4-T2 level. Electromyographic examination revealed bilateral brachial plexus
      palsy. The diagnosis was of brachial plexus palsy and congenital Horner syndrome
      due to congenital cervicothoracic SM. According to our best knowledge, this
      association has not been reported in the literature.

PMID- 19765927
TI  - [Glivec induced autoimmune hepatitis].

PMID- 19765928
TI  - Nodular regenerative hyperplasia of the liver, celiac disease and Sjogren's
      syndrome in a child.

PMID- 19765929
TI  - [Virtual chromoendoscopy].
AB  - Precise endoscopic assessment of gastrointestinal mucosal features is important
      in order to detect neoplastic lesions at an early stage. Electronic virtual
      chromoendoscopy markedly improves capillary pattern contrast and is an in vivo
      method for visualizing microvessel morphological changes in superficial
      neoplastic lesions. The scientific basis for this technique is that short
      wavelength light falls within the hemoglobin absorption band, thereby
      facilitating clearer visualization of vascular structures and pit pattern. Narrow
      Band Imaging (NBI, Olympus) and Multi-Band Imaging (FICE) are real-time, on
      demand endoscopic imaging techniques available with high-definition endoscope.
      Potential indications include both the detection of premalignant lesions and
      differentiation between neoplastic and non-neoplastic lesions. The ease and
      readiness of use and the routine availability of virtual chromoendoscopy will
      probably contribute to its popularity. This does not alleviate the need to better
      define the role of these techniques in daily endoscopy practice by conducting
      well-designed prospective studies.

PMID- 19765930
TI  - Sexually transmitted HCV infection and reinfection in HIV-infected homosexual
      men.
AB  - Multiple, concomitant or successive hepatitis C virus (HCV) infections have been
      described in injection drug users and following organ transplantation and blood
      transfusion. However, data on sexual HCV reinfection is scarce. We report sexual
      HCV reinfection following viral eradication of a first HCV infection in two
      homosexual HIV-infected men. The first patient acquired HCV genotype 4 infection
      after resolution of an initial acute HCV genotype 1a infection. The second
      patient was infected with genotype 1a HCV following remission of an initial acute
      HCV genotype 4c/d infection. The two subjects were successfully treated with
      peginterferon alpha-2a and ribavirin for their first and second infection and
      achieved a sustained virological response on both occasions. Unprotected anal
      intercourse with multiple partners known to be HIV-positive (serosorting) was the
      only risk factor for HCV transmission reported by both patients. Therefore,
      sexual HCV reinfection can occur in homosexual men having unprotected sex and
      "serosorting" should be considered a risk factor for the sexual transmission of
      HCV.

PMID- 19765931
TI  - [Adenocarcinoma of gallbladder revealed by acanthosis nigricans].

PMID- 19765932
TI  - Below knee angioplasty in elderly patients: predictors of major adverse clinical
      outcomes.
AB  - AIM: To determine predictors of clinical outcome following percutaneous
      transluminal angioplasty (PTA) in elderly patients with below knee
      atherosclerotic lesions causing intermittent claudication (IC) or critical limb
      ischaemia (CLI). MATERIALS AND METHODS: Over 7.5 years, 76 patients (CLI 72%, n =
      55) underwent below knee PTA. The composite end-point of interest was major
      adverse clinical outcome (MACO) of the treated limb at follow-up which was
      defined as clinical failure, need for subsequent endovascular or surgical
      revascularization or amputation. Actuarial freedom from MACO was assessed using
      Kaplan-Meier curves and multivariable Cox proportional hazards regression.
      RESULTS: IC was improved in 95% at mean 3.4 years (range 0.5-108 months).
      Successful limb salvage and ulcer healing were seen in 73% with CLI. Most
      failures were in the CLI group (27% CLI vs. 5% IC), with an amputation rate of
      16% for CLI vs. 5% for IC and persistent ulceration in 24% of CLI. Significant
      independent predictors of MACO were ulceration (hazard ratio 4.02, 95% CI = 1.55
      10.38) and family history of atherosclerosis (hazard ratio 2.53, 95% CI = 1.1
      5.92). CONCLUSION: Primary below knee PTA is a feasible therapeutic option in
      this elderly population. Limb ulceration and family history of atherosclerosis
      may be independent predictors of adverse outcome.

PMID- 19765933
TI  - Hymenobacter tibetensis sp. nov., a UV-resistant bacterium isolated from Qinghai
      Tibet plateau.
AB  - A brick-red-pigmented strain (XTM003(T)) isolated from the Qinghai-Tibet plateau
      was investigated using a polyphasic taxonomy approach. Phylogenetic analyses
      based on 16S rRNA gene sequence indicated that the organism belonged to the genus
      Hymenobacter. The predominant menaquinone was MK7. The major fatty acids included
      iso-15:0, 16:1w5c and summed feature 3 (C(16: 1)omega7c and/or C(16: 1)omega6c).
      The G+C content of the DNA was 55.8%. In addition, DNA-DNA hybridization studies
      demonstrated that strain XTM003(T) had a relatedness value of 50.7% with the
      phylogenetically most closely related species Hymenobacter norwichensis DSM
      15439(T). Based on the results of phenotypic characteristics and DNA-DNA
      hybridization studies, strain XTM003(T) is considered to represent a novel
      species, for which the name Hymenobacter tibetensis sp. nov. is proposed. The
      type strain is XTM003(T) (=CCTCC AB 207089(T)=NRRL B-51271(T)).

PMID- 19765934
TI  - Dog bite wound infection by Pasteurella dagmatis misidentified as Pasteurella
      pneumotropica by automated system Vitek 2.

PMID- 19765935
TI  - Visual DNA microarrays for simultaneous detection of human immunodeficiency virus
      type-1 and Treponema pallidum coupled with multiplex asymmetric polymerase chain
      reaction.
AB  - Based on gold label silver stain and coupled with multiplex asymmetric polymerase
      chain reaction (PCR) analysis, we developed the visual DNA microarray for
      simultaneous, sensitive, and specific detection of human immunodeficiency virus
      type-1 (HIV-1) and Treponema pallidum. The 5'-end amino-modified oligonucleotides
      were immobilized on glass surface, which were used as the capturing probes to
      bind the complement biotinylated target DNA. The gold-conjugated streptavidins
      were introduced to the microarray for specific binding to biotin. The black image
      of microarray spots, which were the result from the precipitation of silver onto
      nanogold particles and bound to streptavidins, was visualized and accounted as
      the detection of biotinylated target DNA. Multiplex asymmetric PCR products of
      HIV-1 and T. pallidum and Bacillus subtilis (used as positive control) were
      performed for preparing the abundant biotinylated single-stranded target DNA of
      which could affect detection efficiency and sensitivity of hybridization on
      microarray. One hundred sixty-nine clinical samples of HIV-1 and T. pallidum from
      infected patients were tested using the homemade DNA microarrays. The results
      were identical to those shown in the assays of ELISA and fluorescence
      quantitative real-time PCR. Our results demonstrate that we have developed the
      visual gene detection technique, which is of high sensitivity and specificity; it
      may have potential in clinical applications.

PMID- 19765936
TI  - Digital Epipen(r) injection: a case of conservative management.

PMID- 19765937
TI  - Spurge contact dermatitis.

PMID- 19765938
TI  - Ulcers in the eye.

PMID- 19765939
TI  - Polythene predicament.
AB  - BACKGROUND: Hypoxemia complicating care during ventilation is a common problem.
      OBJECTIVE: To describe an unusual cause of hypoxemia with fluctuating airway
      pressures in an invasively ventilated, organophosphate-poisoned patient. CASE
      REPORT: A 40-year-old man being treated for organophosphate poisoning developed
      episodes of high airway pressure during mechanical ventilation. These episodes
      initially settled spontaneously. Detailed evaluation failed to reveal any patient
      , airway-, or ventilator-related cause for the high airway pressures. On the
      fourth hospital day, one such episode of high peak airway pressures persisted and
      was associated with low tidal volumes and oxygen desaturation. Several attempts
      at suctioning were unsuccessful and the suction catheter could not be advanced.
      When the endotracheal tube was removed, a piece of polythene was found at the
      lower end of the endotracheal tube. This polythene probably resulted in this
      unusual problem by behaving like a flap valve, causing fluctuating airway
      pressures initially, and high airway pressures subsequently. There were no
      further episodes of high airway pressure, and a bronchoscopy did not reveal any
      residual pieces of polythene. On subsequent questioning, it was revealed that the
      patient was discovered unconscious with a stuffed polythene cover containing the
      poison in his mouth. It was likely that the polythene was aspirated when the
      patient was drowsy, or it was pushed into the airway during intubation.
      CONCLUSION: The importance of careful visualization of the oral cavity before
      intubation is illustrated in this report. A bronchoscopy may aid in the
      evaluation of intermittent high airway pressures once pneumothorax and
      bronchospasm are excluded and should be considered early if an obvious cause for
      the high airway pressure is not evident.

PMID- 19765940
TI  - Intravenous tissue plasminogen activator for stroke: a review of the ECASS III
      results in relation to prior clinical trials.
AB  - BACKGROUND: Intravenous tissue plasminogen activator (IV tPA) is currently
      approved by the Food and Drug Administration for use in acute ischemic stroke
      patients up to 3 h from symptom onset, based primarily on the National Institute
      of Neurological Disorders and Stroke tPA trials published in 1995. The most
      recent trial published with IV tPA in stroke (European Cooperative Acute Stroke
      Study [ECASS] III) studied patients between 3 and 4.5 h from symptom onset and
      found a benefit to treatment in the rate of favorable outcome when compared to
      placebo, with no difference in mortality. OBJECTIVES: To examine the patient
      selection criteria and primary outcomes in ECASS III as compared to prior
      clinical trials and the current practice in the United States to determine how
      these new data could be applied to clinical practice. DISCUSSION: With the
      exception of the longer time from symptom onset to treatment, ECASS III used more
      restrictive patient selection criteria than is the current practice in the United
      States to determine patient eligibility for IV tPA. CONCLUSIONS: Based on the
      combined data from all trials, the benefits of thrombolysis with IV tPA for acute
      ischemic stroke outweigh the risks of treatment for selected patients up to 4.5 h
      from symptom onset. It is already known that thrombolysis is not beneficial for
      all stroke patients and strict criteria should be applied before treatment. As
      time from symptom onset increases, the need for careful patient selection likely
      also increases.

PMID- 19765941
TI  - Cannabinoid hyperemesis: a case series.
AB  - BACKGROUND: Cannabinoid use is prevalent in the United States, with recent
      reports of increased usage among younger Americans. Traditionally, cannabinoids
      have been used recreationally or as antiemetics; however, recent reports suggest
      that chronic abuse can result in the paradoxical effect of a cyclic vomiting
      syndrome, termed cannabinoid hyperemesis. OBJECTIVE: We report on this recently
      described clinical syndrome characterized by severe nausea and hyperemesis in the
      setting of chronic cannabinoid use. CASE REPORTS: We report the cases of 3
      patients who presented to two academic emergency departments (EDs) on multiple
      occasions with nausea and vomiting in the setting of chronic cannabinoid use.
      There were extensive medical evaluations and frequent inpatient hospital
      admissions before the diagnosis of cannabinoid hyperemesis was considered.
      CONCLUSION: With the relatively high prevalence of cannabinoid use in the United
      States and increasing interest in the applications of marijuana for therapeutic
      purposes, this entity may be encountered in the ED. Cannabinoid hyperemesis
      should be considered in the differential diagnosis of patients presenting with
      similar symptoms.

PMID- 19765942
TI  - Pulmonary embolism risk stratification: pulse oximetry and pulmonary embolism
      severity index.
AB  - BACKGROUND: Risk stratification of pulmonary embolism (PE) patients is important
      to determine appropriate management. OBJECTIVES: We evaluated two published risk
      stratification tools in emergency department (ED) PE patients: a pulse oximetry
      cutoff below 92.5% oxygen (at 5280 feet elevation) and the Pulmonary Embolism
      Severity Index (PESI). METHODS: Electronic medical records of all patients
      diagnosed with PE were abstracted to identify their triage vital signs, co
      morbidities, and adverse short-term outcomes (AO) either requiring interventions
      (defined as respiratory failure, hypotension requiring pressors, and hemodynamic
      impairment requiring thrombolytics) or resulting in death. We applied these
      models to our ED PE patients and assessed their performance. RESULTS: There were
      168 PE patients identified, with an overall AO rate of 7.1% (12/168), including a
      3.0% mortality rate. A room-air pulse oximetry cutoff of 92.5%, for values
      measured at 5280 feet, classified 89/136 patients as low risk, 1.1% of which had
      an AO, and 47/136 patients as high risk, of which 10.6% had AO. This pulse
      oximetry cutoff had a sensitivity of 83% (95% confidence interval [CI] 36-99%),
      specificity of 68% (95% CI 58-76%), and a negative predictive value (NPV) of 99%
      (95% CI 93-100%). PESI classified 91/168 patients as low risk (class I or II):
      2.2% had AO but none died, and 77/168 were classified as high risk (class III,
      IV, or V), with an AO rate of 13.0%. A PESI cutoff score of II had a sensitivity
      of 83% (95% CI 52-98%), specificity of 57% (95% CI 49-65%), and NPV of 98% (95%
      CI 92-100%). CONCLUSION: Both PESI and pulse oximetry measurements are moderately
      accurate identifiers of low-risk patients with PE.

PMID- 19765943
TI  - Improving straight needle safety: an alternate method.

PMID- 19765944
TI  - Salvia divinorum: exposures reported to a statewide poison control system over 10
      years.
AB  - BACKGROUND: Salvia divinorum, a hallucinogenic herb, has in recent years become
      popular among teenagers and young adults. Salvia is presently marketed as a
      "legal" alternative to other drugs of abuse, but little is known about the
      clinical toxicity of this substance. OBJECTIVES: The purpose of this study is to
      describe the clinical and demographic features of this emerging substance of
      recreational abuse using data obtained from the records of a poison control
      center. METHODS: We performed retrospective review of exposures to the herbal
      hallucinogen Salvia divinorum as reported to the California Poison Control System
      (CPCS) over the last 10 years. Demographic and clinical data were collected and
      compiled from the computerized records of the CPCS for the search terms "salvia"
      and "sage." RESULTS: There were 37 exposures to S. divinorum and 96 exposures to
      non-hallucinogenic Salvia species. Eighteen (49%) of the exposures were to S.
      divinorum alone. Intentional Salvia exposures resulted in a variety of
      neurologic, cardiovascular, and gastrointestinal effects. Notably, the use of
      concomitant substances of abuse was associated with a high rate of complications
      and psychomotor disturbances. CONCLUSIONS: Intentional use of S. divinorum,
      whether alone or in combination with alcoholic beverages and other drugs, causes
      neurologic, cardiovascular, and gastrointestinal effects. This poison-center
      based review helps to characterize the clinical toxicity of S. divinorum, but
      more clinical and pharmacologic research is warranted for this rapidly emerging
      substance of abuse.

PMID- 19765945
TI  - [HPV immunization for the prevention of cervical cancer].
AB  - CONTEXT: Human Papillomaviruses (HPV) infect epithelial cells of the skin and
      mucosae. Mucosal high-risk HPV types (mainly HPV 16 and 18) are involved in the
      development of cervical cancer, one of the most common cancers in young women.
      HPV infection is usually asymptomatic and clears spontaneously, but 10 - 15 % of
      high-risk HPV infections are persistent and increase the risk of precancerous and
      cancerous lesions of the cervix. Two HPV vaccines have been licensed to provide
      protection against cervical cancer. OBJECTIVES: To report the different aspects
      of HPV infection in order to improve the understanding of the particular problems
      of HPV vaccination and to review the most recent findings related to HPV
      vaccines, particularly regarding the protective efficacy of vaccines and the
      roles of adjuvants and immune response in protection. METHODS: Articles were
      selected from the PubMed database (National Library of Medicine- National
      Institute of Health) with the following Keywords "HPV", "Prevention", "HPV
      vaccines", "Immune response", "Antibody". Abstracts of oral presentations from
      international meetings were also selected for the more recent findings. a
      critical analysis of the majority of papers published was undertaken and relevant
      information summarized. RESULTS: Virus-like particle production by expressing the
      major protein of the HPV capsid was carried out in the early 90's, leading to the
      recent development of two HPV vaccines. These vaccines are now licensed in many
      countries and have been demonstrated to be highly immunogenic. In subjects that
      are non-infected at the time of vaccination, HPV vaccines are highly effective in
      preventing persistent HPV 16 - 18 infections (90 %) and precursors lesions of
      cervical cancer associated with these two HPV types (close to 100 %). Clinical
      trials have also confirmed that HPV vaccines are well tolerated by recipients.
      CONCLUSIONS: The present paper is a detailed review published in French on HPV
      vaccines, their efficacy in the prevention of HPV infections and unresolved
      questions regarding the use of HPV vaccines. This report also includes biological
      and immunological information to improve the understanding of HPV vaccination.

PMID- 19765946
TI  - Clinically significant avoidance of public transport following the London
      bombings: travel phobia or subthreshold posttraumatic stress disorder?
AB  - Following the London bombings of 7 July 2005 a "screen and treat" program was set
      up with the aim of providing rapid treatment for psychological responses in
      individuals directly affected. The present study found that 45% of the 596
      respondents to the screening program reported phobic fear of public transport in
      a screening questionnaire. The screening program identified 255 bombing survivors
      who needed treatment for a psychological disorder. Of these, 20 (8%) suffered
      from clinically significant travel phobia. However, many of these individuals
      also reported symptoms of posttraumatic stress disorder [PTSD]. Comparisons
      between the travel phobia group and a sex-matched group of bombing survivors with
      PTSD showed that the travel phobic group reported fewer re-experiencing and
      arousal symptoms on the Trauma Screening Questionnaire (Brewin et al., 2002). The
      only PTSD symptoms that differentiated the groups were anger problems and feeling
      upset by reminders of the bombings. There was no difference between the groups in
      the reported severity of trauma or in presence of daily transport difficulties.
      Implications of these results for future trauma response are discussed.

PMID- 19765947
TI  - Outcome of the use of stent grafts to salvage failed arteriovenous accesses.
AB  - BACKGROUND: Since elements of the Dialysis Outcome Quality Initiative (K/DOQI)
      were implemented a decade ago, there has been a reduction in mortality for
      patients on hemodialysis. As patient longevity has increased, AV access site
      preservation by salvaging failed arteriovenous (AV) accesses has become
      increasingly important. However, efforts to salvage an AV access must be balanced
      against futile and expensive procedures. The Viabahn Endoprosthesis is a self
      expandable stent graft (SG) that can be used to treat vein rupture or fibrotic
      lesions with significant elastic recoil following balloon angioplasty. The
      literature comprising the outcome of the use of SGs in salvaging failed AV
      accesses is limited. The purpose of this study is to determine the outcome of
      failed AV accesses treated with SGs and to identify patient or graft factors
      predictive of success. METHODS: The vascular access database and office,
      hospital, and dialysis unit records were retrospectively reviewed to identify all
      patients who underwent placement of an SG for the treatment of a thrombosed AV
      access between September 2004 and December 2007. Mean patient follow-up was 6
      months. The K/DOQI goal for patency following a surgical intervention (6 months
      or later) was used to determine procedure success or failure. Kaplan-Meier life
      table analysis was used to determine patency. Patient demographics and graft
      factors (location, diameter, length) were analyzed to identify predictors of
      success. RESULTS: Fifty-five SGs were placed in 48 patients (males, 29%; mean
      age, 61 years; diabetes mellitus, 47%) with a failed AV access. The indications
      were to treat significant elastic recoil or vein rupture following balloon
      angioplasty (47 patients) and to treat an AV graft seroma (1 patient). Cost for
      the VE ranged from $2337 to $3367 per patient. The procedure was deemed
      successful (patent at 6 months) in 29 + or - 7% of cases. Procedure success was
      not influenced by AV access location, endoprosthesis size (diameter or length),
      or patient demographic factors (p > 0.05). CONCLUSION: Use of the SG to salvage
      AV accesses falls short of the current K/DOQI clinical outcome goals for
      successful surgical intervention in the majority of cases. Given these results
      and the cost of the SG, its use is indicated in cases where AV access salvage
      will have an impact on long-term survival such as for patients in whom there are
      few options for new access placement. Further studies are needed to compare the
      SG to less costly options, such as angioplasty alone or angioplasty with the use
      of bare metal stents.

PMID- 19765948
TI  - Combined distal venous arterialization and free flap for patients with extensive
      tissue loss.
AB  - BACKGROUND: We evaluated the mid-term outcome of distal venous arterialization
      (DVA) and the role of a combined free flap as a bridgehead for blood supply.
      METHODS: In the past 5 years, nine patients with extensive tissue loss and
      lacking graftable distal arteries underwent DVA. These consisted of four primary
      DVAs, three combined DVA and free flap procedures, and two adjuvant DVAs for
      hemodynamically failed distal bypasses. After nine primary DVAs, three redo DVAs
      were performed for early failure. Etiologies were four Buerger disease and five
      arteriosclerosis obliterans, including three dialysis patients. RESULTS: Among
      the nine DVA cases, there were five primary failures: two underwent amputation,
      two had successful redo DVA, and the remaining one did not require redo DVA.
      Primary patency, secondary patency, and limb salvage rates were 44.4%, 55.6%, and
      77.8%, respectively. The postoperative period was 1-36 months (median 12).
      Angiography demonstrated DVA was effective in the early period, and development
      of collaterals or a capillary network from the free flap replaced the DVA
      function in the intermediate period. CONCLUSION: DVA can be effective as a
      procedure for limb salvage in patients without graftable distal arteries, and a
      combined free flap is effective and functions as a bridgehead for blood supply to
      the ischemic zone.

PMID- 19765949
TI  - The role of experience on judgments of dysphonia.
AB  - OBJECTIVES: The objectives of the study were (1) to determine differences in
      judgments of overall severity (OS) and vocal effort (VE) of dysphonic speech when
      judgments were made by experienced and inexperienced listeners, and when self
      rated by individuals with dysphonia; and (2) to determine relationships between
      auditory-perceptual judgments of voice and voice handicap. STUDY DESIGN:
      Prospective and exploratory. METHODS: Twenty speakers with dysphonia and four
      normal controls provided speech recordings. Participants judged their own speech
      samples for OS and VE and completed the Voice Handicap Index (VHI). Twenty-four
      inexperienced and 10 experienced listeners evaluated the same speech samples for
      OS and VE using 100-mm visual analog scales. RESULTS: No differences were found
      for judgments of OS and VE across the groups. However, relationships between
      judgments made by experienced and inexperienced listeners were strong, whereas
      those between individuals with dysphonia and other listeners were weak to
      moderate. All listeners' judgments of voice were moderate predictors of VHI
      scores, with patient-perceived VE and clinician-rated OS being relatively
      strongest. CONCLUSIONS: Although there is no systematic effect of listener
      experience on judgments of dysphonia, individuals with dysphonia appear to self
      rate their voices using different perceptual strategies than other listeners.
      Auditory-perceptual measures are only moderately related to voice handicap
      scores, indicating that they are complementary measures of voice.

PMID- 19765950
TI  - Hand-injured patients' experiences of cold sensitivity and the consequences and
      adaptation for daily life: a qualitative study.
AB  - STUDY DESIGN: Qualitative descriptive. INTRODUCTION: Cold sensitivity is a common
      and persistent complaint after hand injuries. PURPOSE OF THE STUDY: To explore
      the experiences of severe cold sensitivity, its consequences for daily life, and
      the strategies for enduring and enabling occupation. METHODS: Fifteen hand
      injured patients with abnormal cold sensitivity were interviewed. The transcribed
      text was analyzed using manifest and latent content analysis. Experiences of
      triggering factors, symptoms, and relieving strategies were described. RESULTS:
      The consequences and adaptation in daily life entailed a change in life roles, a
      struggle to maintain self-image and changed occupational performance and/or
      occupational patterns. CONCLUSIONS: Our findings highlight the importance of a
      holistic approach, including a screening of patients' occupational roles and
      patterns as well as psychosocial needs, to obtain the information needed to
      support patients with severe cold sensitivity to achieve a sense of control and
      self-mastery. LEVEL OF EVIDENCE: not applicable.

PMID- 19765951
TI  - Clinical commentary in response to: Relationship between patient satisfaction and
      functional outcome metrics 3 months after surgical treatment for distal radius
      fractures.

PMID- 19765952
TI  - Bioavailability of catechins from ready-to-drink tea.
AB  - OBJECTIVE: Because consumption of teas may be associated with potential health
      benefits due to its content in polyphenols and in Western countries the
      consumption of tea is equally divided between the hot and the ready-to-drink
      (RTD) cold versions of this typical beverage, the aim of this work was to study
      the absorption and metabolism of flavan-3-ols in human volunteers after the
      ingestion of a commercial RTD tea. METHODS: A feeding study was carried out in 20
      healthy human volunteers and urine samples were collected for 24h after tea
      ingestion. Flavan-3-ols-derived molecules were identified and quantified in urine
      samples by high-performance liquid chromatography with tandem mass spectrometric
      detection. RESULTS: Eight relevant metabolites were identified in urine, all
      modified flavan-3-ols with the exception of unmetabolized gallic acid. The
      urinary excretion of flavan-3-ols was equal to 7.2% of the intake with tea.
      Gallic acid, which was abundant in the RTD tea used in this study, reached a 4.5%
      of the drunken amount. CONCLUSIONS: The bioavailability values observed are in
      agreement with previous reports, although the dosage of polyphenols ingested in
      this study is remarkably lower. Moreover, the use of a group of 20 volunteers,
      more than the average number of subjects used for usual human acute-feeding
      studies involving polyphenols, provides additional credibility to the results.
      After drinking the RTD ice tea used in this study, the internal compartments are
      exposed to non-marginal doses of flavanols and flavanol metabolites up to 24h.

PMID- 19765953
TI  - Short-term high dietary calcium intake during bedrest has no effect on markers of
      bone turnover in healthy men.
AB  - OBJECTIVE: Immobilization and space flight are causes of disuse osteoporosis.
      Increasing calcium intake may counteract this disuse-induced bone loss. METHODS:
      We conducted two bedrest experiments (crossover design: bedrest versus ambulatory
      control) in a metabolic ward, studying the effect of 1000 mg/d of calcium intake
      (study A, length of intervention 14 d) compared with that of a high calcium
      intake of 2000 mg/d (study B, 6 d) on markers of bone turnover. Both studies were
      randomized, controlled studies with the subjects staying under well-controlled
      environmental conditions (study A, 9 male subjects, age 23.6+/-3.0 y; study B, 8
      male subjects, age 25.5+/-2.9 y). Blood was drawn to analyze serum calcium,
      parathyroid hormone, procollagen type I C-terminal propeptide, and bone alkaline
      phosphatase. Urine (24-h) was collected for analysis of calcium, C-terminal
      telopeptide of collagen type I, and N-terminal telopeptide of collagen type I.
      RESULTS: In both studies, serum calcium levels remained unchanged. Procollagen
      type I C-terminal propeptide was lower (P=0.03) in the bedrest phase than in the
      ambulatory phase in study A and tended to be lower (P=0.08) in bedrest in study
      B, whereas bone alkaline phosphatase was not affected in either study. Urinary
      calcium excretion was greater during bedrest than during the ambulatory phase
      (study A, P=0.005; study B, P=0.002). C-terminal telopeptide of collagen type I
      excretion was also greater during bedrest in both studies (study A, P<0.001;
      study B, P<0.001). CONCLUSION: Doubling calcium intake to 2000 mg/d does not
      prevent increased bone resorption induced by bedrest.

PMID- 19765954
TI  - The safety of oral use of L-glutamine in middle-aged and elderly individuals.
AB  - OBJECTIVE: To evaluate the safety of nutraceutical oral administration of L
      glutamine (L-Gln) in middle-aged and elderly individuals. METHODS: In this
      randomized, crossover, double-blind clinical study, 30 residents of a long-term
      care institution, selected according to a modified SENIEUR protocol (Working
      Party of the EURAGE Concerted Action Programme on Ageing of the European
      Community), were studied. Fourteen subjects received orally 0.5 g kg(-1) d(-1) of
      L-Gln and 16 received calcium caseinate for 14 d, followed by a 5-d washout.
      Supplements were switched for the second 14-d trial. Laboratory tests for hepatic
      and renal functions and ammonemia were performed and the estimated glomerular
      filtration rate (eGFR) was calculated. RESULTS: Of the 30 subjects, 16 were men,
      mean age was 69+/-8.8 y, average weight was 61.8+/-14.2 kg, and mean serum
      albumin was 4.0+/-0.3g/dL. Neither adverse clinical effects nor clinically
      significant laboratory changes were noted during L-Gln supplementation. There was
      no difference in ammonemia between the groups. There were statistically but not
      clinically significant increases in plasma urea nitrogen and creatinine
      concentrations. There was no significant decrease in eGFR during calcium
      caseinate supplementation (-2.9%). The eGFR decreased significantly after L-Gln
      supplementation (-13.3%) but well below the 25% limit for biologic significance.
      CONCLUSION: Increases in serum urea nitrogen and creatinine and decrease in eGFR
      are probably due to difficulties by older kidneys in metabolizing the
      supplemented protein sources. Although not clinically significant, those
      alterations impose a rigorous control on the evaluation parameters of renal
      function during oral L-Gln supplementation, with doses of 0.5 g kg(-1) d(-1) in
      middle-aged and elderly individuals.

PMID- 19765955
TI  - Do subclinical electrographic seizure patterns affect heart rate and its
      variability?
AB  - PURPOSE: Autonomic symptoms during seizures may provide information on seizure
      onset zone. We investigated whether changes in heart rate (HR) and HR variability
      (HRV) occur during subclinical electrographic seizure patterns, and whether these
      have a localising/lateralising value. METHODS: EEG and ECG recordings of
      pharmacoresistant epilepsy patients who underwent intracranial video-EEG
      telemetry were reviewed. Ultra-short-term HRV expressed as standard deviation of
      the mean before, during and after the subclinical seizure pattern was determined
      in 10s epochs. Statistics were done with a linear mixed regression model. Values
      are expressed as mean+/-SD. RESULTS: 26 patients (38+/-10 years, 13 of either
      gender) have been included; 7 patients with temporal lobe epilepsy (TLE) of
      either side as well as 7 (right-sided lesion) and 5 patients (left-sided lesion)
      with frontal lobe epilepsy (FLE). A total of 74 subclinical events (2-3 per
      patients) were analysed. Pooled data for HR only weakly increased during and
      after the subclinical pattern with a mean HR of 80+/-10 bpm before to 82+/-11 bpm
      during (p=0.03) and 81+/-10 bpm after subclinical patterns (p=0.06). HR was
      higher in patients with left TLE as compared to right TLE (p=0.001). In FLE
      patients only, the change in HR was correlated with the spatial extent of
      electrographic pattern localised (p=0.03). Mean HRV did not change during or
      after subclinical patterns. HRV was; however, lower in TLE patients with left
      sided subclinical patterns as compared to right-sided patterns (pre-event HRV
      left 13+/-6 ms, right 34+/-16 ms). CONCLUSIONS: Our data revealed only minimal
      changes in autonomic cardiac function during highly localised electrographic
      seizure patterns and this had no localising/lateralising value.

PMID- 19765956
TI  - On 29Si NMR relaxation as a structural criterion for studying paramagnetic
      supermicroporous silica-based materials: silica-based materials incorporating
      Mn2+ ions into the silica matrix of SiO2-Al2O3-MnO.
AB  - Supermicroporous paramagnetic materials SiO(2)-Al(2)O(3)-MnO and SiO(2)-MnO with
      different manganese concentrations have been probed by solid-state (29)Si NMR and
      magnetic susceptibility measurements. The (29)Si T(1) and T(2) experiments,
      performed in static and spinning samples, have resulted in determination of
      electron relaxation times, providing, in turn, quantitative interpretations of
      (29)Si T(1) times in terms of distances Mn-Si. The NMR relaxation data have
      revealed (29)Si T(1) time distributions, which are close to Gaussian and observed
      as different T(1) values obtained in MAS NMR experiments for isotropic (29)Si
      resonances and their sidebands. Such (29)Si T(1) distributions, being a common
      phenomenon in paramagnetic silica-based materials, can be however masked by the
      bulk magnetic susceptibility (BMS) effects increasing with concentrations of
      paramagnetic centers. The presence of T(1) distributions, in itself, is not a
      criterion for incorporation of paramagnetic ions into the silica matrix or its
      surface. However, a quantitative analysis of the experimentally-observed short
      (29)Si T(1) components, based on the well-determined electron relaxation times,
      can provide such a criterion.

PMID- 19765957
TI  - Interaction of lipidated GBV-C/HGV NS3 (513-522) and (505-514) peptides with
      phospholipids monolayer. An AFM study.
AB  - Lipidation of a short hydrophilic peptide has the aim to make the molecule
      amphiphilic, which improves its insertion into lipid monolayer and at the same
      time, the tendency to self-assembly. These both properties of two positively
      charged, hepatitis G (GBV-C/HGV) related lipidated peptides--palmitic acid
      derivatives of the fragments: 505-514 and the 513-522 of the NS3 protein
      (respectively Palmitoyl-SAELSMQRRG and Palmitoyl-RGRTGRGRSG) were studied. First,
      using transmission electron microscope (TEM) and atomic force microscope (AFM)
      the tendency to self-assembly in water solution was examined. Both techniques
      confirmed the formation of fibrous aggregates of Palmitoyl-SAELSMQRRG in water
      solution. At the same conditions, any fibrous aggregates of Palmitoyl-RGRTGRGRSG
      were detected neither by TEM nor by AFM. Insertion of the lipidated peptides into
      phospholipids monolayer formed by zwitterionic 1,2-dipalmitoyl-sn-glycero-3
      phosphocholine (DPPC) or negatively charged 1,2-dipalmitoyl-sn-glycero-3-[phospho
      rac-(1-glycerol)] (DPPG) was investigated. Monolayers prepared by Langmuir
      Blodgett method were visualized by AFM. The presence of lipidated peptides in
      phospholipid monolayers produced changes in the monolayers and different
      morphologies of the monolayers were obtained for each of the lipidated peptides.

PMID- 19765958
TI  - Increased plasma xanthine oxidase activity is related to nuclear factor kappa
      beta activation and inflammatory markers in familial combined hyperlipidemia.
AB  - BACKGROUND AND AIMS: Xanthine oxidase (XO) has been described as one of the major
      enzymes producing free radicals in blood. Oxidative stress and inflammatory
      processes have been implicated in the pathogenesis of endothelial dysfunction and
      the progression of atherosclerosis but until now, there is little data about the
      influence of vascular prooxidant systems and inflammation in familial combined
      hyperlipidemia (FCH). Our goal was to evaluate whether XO activity was altered in
      FCH and if it was related to the inflammatory process represented by NFkB, IL-6
      and hsCRP, and assessing the correlation between XO activity and insulin
      resistance (IR). METHOD AND RESULTS: 40 Non-related subjects with FCH and 30
      control subjects were included, all of them non-diabetic, normotensive and non
      smokers. We measured lipid profile, glucose, insulin, uric acid, XO activity,
      malondialdehyde (MDA), IL-6 and hsCRP in plasma and NFkB activity in circulating
      mononuclear cells. Patients with FCH showed significantly higher levels of uric
      acid, XO activity, MDA, NFkB activity, IL-6 and hsCRP than controls. XO activity
      was independently related to NFkB activity with an odds ratio of 4.082; to IL-6
      with an odds ratio of 4.191; and to IR with an odds ratio of 3.830. Furthermore,
      mean NFkB activity, IL-6 levels, and IR were highest in the highest percentile of
      XO activity. CONCLUSIONS: Subjects with FCH showed increased XO and NFkB
      activities and low grade inflammatory markers related to atherosclerosis. XO
      activity was correlated with higher inflammatory activity and IR. These data
      could explain, in part, the high cardiovascular disease risk present in these
      patients.

PMID- 19765959
TI  - The APOA5-1131 T>C variant enhances the association between RBP4 and
      hypertriglyceridemia in diabetes.
AB  - BACKGROUND AND AIM: Type 2 diabetic patients have an increased prevalence of
      hypertriglyceridemia. RBP4 has been associated with insulin resistance and
      hypertriglyceridemia in obesity, the metabolic syndrome and type 2 diabetes.
      APOA5 is proposed to be a genetic modulator of triglycerides. The aim of this
      study was to evaluate the relationship between RBP4 plasma levels and lipid
      disturbances and to determine the impact of the APOA5-1131 T>C variant on this
      relationship in type 2 diabetic patients. METHODS AND RESULTS: A total of 165
      type 2 diabetic patients were included in the study. RBP4 plasma levels and the
      APOA5-1131 T>C variant were determined and the complete lipid profile was
      assessed by sequential ultracentrifugation. RBP4 was positively correlated with
      triglyceride levels in plasma and with all the components of triglyceride-rich
      lipoproteins. Despite the fact that a statistically significant relationship
      between the APOA5 genetic variant and RBP4 plasma levels was not found, the
      hypertriglyceridemic effect of high RBP4 levels was enhanced by the presence of
      the APOA5-1131 T>C genetic variant. Correlation coefficients were 2-fold higher
      for TC carriers compared to TT carriers with regard to RBP4 plasma levels and all
      the components of triglyceride-rich lipoproteins. Those type 2 diabetic patients
      with high RBP4 plasma concentrations and who were TC carriers showed an increased
      incidence of hypertriglyceridemia (OR=7.46, P=0.010). CONCLUSION: RBP4 is
      associated with hypertriglyceridemia in type 2 diabetic patients. The RBP4 effect
      is conditioned by the presence of the APOA5-1131 T>C genetic variant.

PMID- 19765960
TI  - Protective effects of aqueous extract of Artemisia campestris against puffer fish
      Lagocephalus lagocephalus extract-induced oxidative damage in rats.
AB  - The aerial parts of Artemisia campestris are often used in Tunisian poisoning
      cases and are known to possess significant antioxidant activities. The objective
      of this study is to evaluate the protective effects of an aqueous extract (5g/l)
      of A. campestris leaves and stems (AE), on oxidative damages induced by liver
      extract (LT) from poisonous fish Lagocephalus lagocephalus in Wistar rats. AE was
      found to contain large amounts of K(+), Na(+), Ca(++) and significant antioxidant
      capacities highlighted by high level of polyphenols and scavenging activities for
      DPPH and superoxide anion. LT-injected rats (1ml/100g body wt) for 10 days showed
      (1) a reduced appetite and diarrhea resulting in a lower growth rate than
      controls, (2) a decrease in serum ALT and AST activities suggesting liver
      functional disorders, (3) an increase of serum urea and creatinine and reduced
      serum sodium and potassium concentrations highlighting renal insufficiency and
      (4) an oxidative stress as evidenced by the raise of TBARS and the inhibition of
      SOD, CAT and GSH-Px activities in liver, kidney and brain tissues Absorption of
      AE as a drink, for 20 days (10 pre-treatment days+10 experiment days) did not
      lead significant change of studied parameters but prevented all the disorders
      induced by LT.

PMID- 19765961
TI  - Insights into the nature of human testicular peritubular cells.
AB  - Human testicular peritubular cells are myofibroblast-like cells that surround the
      seminiferous tubules and are responsible for tubular contractility and sperm
      transport. In the last few years, several reports have augmented this simplified
      view, showing that peritubular cells are not only structural cells but also
      actively secrete paracrine mediators, thereby influencing the homeostasis of the
      testicular environment. This review is focussed on general aspects and functions
      of testicular peritubular cells, their potential role in male infertility and
      also on the recently described in vitro culture systems of human testicular
      peritubular cells, which will enable us to gain deeper insight into the
      regulation and functions of this peculiar cell type in health and disease.

PMID- 19765962
TI  - Temporal synergism of neurotransmitters (serotonin and dopamine) affects
      testicular development in mice.
AB  - The temporal phase relation of circadian oscillations is reported to regulate
      reproduction in many seasonally breeding avian and mammalian species, but its
      role in the reproductive regulation of continuous breeders is not yet known.
      Hence in the present study, six experimental groups of 3-week-old male Parkes
      strain mice, Mus musculus, were injected with 5-hydroxytryptophan (5-HTP,
      serotonin precursor) and L-dihydroxyphenylalanine (L-DOPA, dopamine precursor) at
      intervals of 0, 4, 8, 12, 16 or 20 hr (5mg/100g body weight per day for 13 days).
      Control mice received two daily injections of normal saline. When observed 24
      days post-treatment, 8-hr mice exhibited low body weight and suppression of
      gonadal activity (spermatogenesis, sperm count/motility/viability and plasma
      testosterone concentration), while body weight and degree of gonadal development
      were higher in the 12-hr mice as compared to the controls. It is concluded that
      normal somatic and gonadal growth of pre-puberal mice may be suppressed with an 8
      hr phase relation of circadian serotonergic and dopaminergic oscillations. On the
      other hand, a 12-hr phase relation accelerated the rate of gonadal maturation,
      while other relations led to more or less similar gonadal development as in the
      control mice. This study suggests the importance of circadian organization as a
      function of specific temporal phase relations of neural oscillations in the
      maturation of gonads. Although the exact mechanism still needs to be
      investigated, this seems to be mediated via effects on the neuroendocrine axis.

PMID- 19765963
TI  - The aqueous extract of Hibiscus sabdariffa calices modulates the production of
      monocyte chemoattractant protein-1 in humans.
AB  - Diet supplementation and/or modulation is an important strategy to significantly
      improve human health. The search of plants as additional sources of bioactive
      phenolic compounds is relevant in this context. The aqueous extract of Hibiscus
      sabdariffa is rich in anthocyanins and other phenolic compounds including
      hydroxycitric and chlorogenic acids. Using this extract we have shown an
      effective protection of cultured peripheral blood mononuclear cells from the
      cellular death induced by H(2)O(2) and a significant role in the production of
      inflammatory cytokines. In vitro, the extract promotes the production of IL-6 and
      IL-8 and decreases the concentration of MCP-1 in supernatants in a dose-dependent
      manner. In humans, the ingestion of an acute dose of the extract (10g) was well
      tolerated and decreased plasma MCP-1 concentrations significantly without further
      effects on other cytokines. This effect was not due to a concomitant increase in
      the antioxidant capacity of plasma. Instead, its mechanisms probably involve a
      direct inhibition of inflammatory and/or metabolic pathways responsible for MCP-1
      production, and may be relevant in inflammatory and chronic conditions in which
      the role of MCP-1 is well established. If beneficial effects are confirmed in
      patients, Hibiscus sabdariffa could be considered a valuable traditional herbal
      medicine for the treatment of chronic inflammatory diseases with the advantage of
      being devoid of caloric value or potential alcohol toxicity.

PMID- 19765964
TI  - The influence of NK alloreactivity on matched unrelated donor and HLA identical
      sibling haematopoietic stem cell transplantation.
AB  - Numerous retrospective studies have been reported analysing the role of HLA
      mismatches that confer donor NK alloreactivity towards the recipient on the
      outcome of haematopoietic stem cell transplantation. A bewildering variety of
      findings have been observed with different studies showing either beneficial or
      deleterious effects on outcome. This review organises the reports into those that
      use similar definitions of NK alloreactivity, suggests possible reasons for such
      disparate results and assesses whether any recommendations can be made in
      relation to donor selection. There is growing evidence that the effect of human
      NK alloreactivity on outcome is transplant protocol dependent. Protocol variables
      most likely to affect outcome are those that influence donor T cell numbers. At
      this time, it is not possible to predict how the outcome of unrelated donor
      transplantation will be affected by HLA mismatches conferring potential donor NK
      alloreactivity.

PMID- 19765965
TI  - Solid phase assays for HLA antibody detection in clinical transplantation.
AB  - The complement dependent microlymphocytotoxicity assay has been used for over 40
      years for detecting HLA antibodies in transplant patients. This method has been
      replaced recently by more sensitive solid phase assays such as ELISA and bead
      based technology including the Luminex method. The introduction of these
      techniques into clinical practice has revealed previously undetected
      sensitisation in some patients and allowed the accurate assignment of antibody
      specificities directed at HLA-DQ and HLA-DP which was not previously possible.
      However it is emerging that despite the advantage of sensitivity some HLA
      antibodies defined by these assays are not associated with hyperacute or acute
      rejection. The role in allograft rejection of antibody titre and non-complement
      fixing antibodies, which are also detected by these methods, are areas currently
      under consideration.

PMID- 19765966
TI  - Tracing retail cannabis in the United States: geographic origin and cultivation
      patterns.
AB  - BACKGROUND: Although cannabis is the most readily available and widely used
      illicit drug in the United States, there remains significant uncertainty about
      the importance of different production regions and trafficking patterns. METHODS:
      We analysed 628 "retail" cannabis seizures from over 50 municipalities across the
      United States for hydrogen and carbon isotope ratios to predict their growth
      locations and environments. RESULTS: Results are presented for 22 consolidated
      retail locations across the United States. Evaluation of specimens from within
      these retail areas suggested that cannabis seizures had region-dependent origins,
      often from both domestic and foreign sources, and although indoor growth was
      common in many areas, there was also regional dependence in the proportions
      cultivated under indoor versus outdoor conditions. CONCLUSION: Street-available
      cannabis exhibits region-specific trafficking patterns, both Mexican- and
      Canadian-grown cannabis are apparently widely available, and indoor-grown
      cannabis appears to be cultivated and trafficked in both warm and cool weather
      localities throughout the United States.

PMID- 19765967
TI  - Surface plasmon resonance imaging for affinity-based biosensors.
AB  - SPR imaging (SPRi) is at the forefront of optical label-free and real-time
      detection. It offers the possibility of monitoring hundreds of biological
      interactions simultaneously and from the binding profiles, allows the estimation
      of the kinetic parameters of the interactions between the immobilised probes and
      the ligands in solution. We review the current state of development of SPRi
      technology and its application including commercially available SPRi instruments.
      Attention is also given to surface chemistries for biochip functionalisation and
      suitable approaches to improve sensitivity.

PMID- 19765968
TI  - Immunochromatographic colloidal carbon-based assay for detection of methiocarb in
      surface water.
AB  - A simple and rapid immunochromatographic assay for a sensitive and inexpensive
      monitoring of methiocarb in surface water was developed using a binding
      inhibition format on a membrane strip. In the assay, detection reagent consisted
      of anti-methiocarb antibody and colloidal carbon-labelled secondary antibody.
      Methiocarb-ovalbumin conjugate was immobilized in a test line of the strip as a
      capture reagent. Colour intensity of the test line in methiocarb-positive assay
      was visually distinguishable from that of negative sample within 10min. The
      optimized semi-quantitative method provided a visual detection limit of 0.5ngmL(
      1). Cross-reactions with other carbamate pesticides were not found (<1%). Only a
      negligible matrix effect of surface water was recognized. In parallel analyses of
      spiked water samples, the assay results were in a good agreement with those of
      ELISA. The stability test indicated the strips could be used at least 2 months
      without change in performance. All characteristics of the visually evaluated
      assay mentioned above were verified by instrumental quantification of colour
      intensity in test lines. The developed immunochromatographic assay offers
      potential as a useful on-site screening tool for environmental analysis.

PMID- 19765969
TI  - Label-free biosensing of a gene mutation using a silicon nanowire field-effect
      transistor.
AB  - We have developed a silicon nanowire field-effect transistor (NWFET) that allows
      deoxyribonucleic acid (DNA) biosensing. The nanowire (NW) was fabricated on a
      silicon-on-insulator wafer to provide effective ohmic contact. The NWFET sensor
      displayed n-channel depletion characteristics. To demonstrate the sensing
      capacity of the NWFET, we employed the BRAF(V599E) mutation gene, which
      correlates to the occurrence of cancers, as the target DNA sequence. The
      threshold voltage of the NWFET increased when the mutation gene was hybridized
      with the capture DNA strands on the nanowire, and decreased to the original level
      after de-hybridization of the gene. The shift in the drain current-gate voltage
      (I(D)-V(G)) curves revealed that the electrical signal had a logarithmic
      relationship with respect to the concentration of the mutation gene of up to six
      orders of magnitude, with the detection limit in the sub-femtomolar level. The
      detection results of mismatched DNA sequences, including one- and five-base
      mismatched DNA strands, could be distinguished from complementary DNA gene by
      this sensor. The excellent electrical results obtained using this label-free
      NWFET sensor suggest that such devices might be potentially useful tools for
      biological research and oncogene screening.

PMID- 19765970
TI  - Optical oxygen sensors based on Pt(II) porphyrin dye immobilized on S-layer
      protein matrices.
AB  - This paper describes the development of planar and fiber optic oxygen sensors
      utilizing surface layer (S-layer) proteins as immobilization matrix for oxygen
      sensitive dyes. S-layer proteins have the intrinsic capability to reassemble into
      two-dimensional arrays in suspension and at interfaces. Due to their crystalline
      character the distribution of functional groups, such as carboxylic groups, is
      repeated with the periodicity of the lattice and thus allows the reproducible and
      geometrically distinct binding of functional molecules. For the development of
      oxygen sensors an oxygen sensitive Pt(II) porphyrin dye was covalently bound to
      the S-layer matrix. Measurement of the oxygen concentration was performed by
      phase modulation fluorimetry. Setups comprising low cost optoelectronic
      components like LEDs and silicon photodiodes were constructed. For both sensor
      setups (planar and fiber optic) variations in the oxygen concentrations resulted
      in distinct and reproducible changes in luminescence lifetime and intensity. The
      luminescence quenching efficiency of these sensors was found to be 1.5-1.9
      (expressed as the ratio of signal under nitrogen and air) which compares well to
      other sensor systems using luminophores embedded in polymer matrices. These
      results demonstrated the application potential of S-layers as immobilization
      matrices in the development of (bio-)sensors.

PMID- 19765971
TI  - Highly sensitive gaseous formaldehyde sensor with CdTe quantum dots multilayer
      films.
AB  - A novel method for the direct detection of gaseous formaldehyde based on the
      fluorescence quenching of CdTe quantum dots (QDs)/polyelectrolyte multilayer
      films (QDMF) was proposed in this paper. The functional multilayer films were
      assembled by layer-by-layer (LBL) deposition of oppositely charged CdTe QDs and
      poly(dimethyldiallylemmonium chloride) (PDDA). Formaldehyde can quench the
      fluorescence of CdTe QDs multilayer films effectively. Under the optimization
      conditions, the fluorescence intensity of QDs decreased linearly with the
      increase of formaldehyde concentration in the range of 5-500ppb. The detection
      limit for formaldehyde was 1ppb. The quenching mechanism of CdTe QDs multilayer
      films by formaldehyde was also studied in detail. This proposed approach was
      simple, rapid and had excellent selectivity and sensitivity for the detection of
      gaseous formaldehyde.

PMID- 19765972
TI  - Highly sensitive immunoassay based on Raman reporter-labeled immuno-Au aggregates
      and SERS-active immune substrate.
AB  - A highly sensitive immunoassay based on surface enhanced Raman scattering (SERS)
      has been developed with a novel immune marker named as Raman reporter-labeled
      immuno-Au aggregates on a SERS-active immune substrate. The features of those
      immune aggregates were characterized by UV-vis extinction spectra, TEM images,
      SEM pictures and SERS spectra. It is found that stable gold aggregates in
      appropriate morphologies can be induced by mixing proper amounts of reporter
      molecules with gold nanoparticles. Based on those reporter-labeled Au aggregates,
      the immune aggregates with high stability can be prepared successfully by
      immobilizing antibody to the surface of the aggregates. Using those easily
      prepared aggregates showing strong SERS activity and high bio-specificity, a
      highly effective SERS-based immunoassay has been performed. Moreover, a SERS
      active immune substrate has been introduced to replace a typical immune substrate
      without any SERS activity. Our experimental results indicate that the SERS-active
      immune substrate makes a certain contribution to the highly sensitive
      immunoassay. As a result, with this proposed immunoassay structure, the
      concentration detection of human-IgG was performed and a calibration curve was
      obtained in the range from 100ngmL(-1) to 100fgmL(-1). This work opens a new
      avenue for sensitive immunoassay and other biochemical analysis based on SERS.

PMID- 19765973
TI  - New horizons at the caudal embryos: coordinated urogenital/reproductive organ
      formation by growth factor signaling.
AB  - The cloaca/urogenital sinus and its adjacent region differentiate into the
      urogenital/reproductive organs. Caudal regression syndrome (CRS; including
      mermaid syndrome), a type of severe cloacal malformation displays hindlimb fusion
      and urogenital organ defects, thus suggesting that such defects are caused by
      several morphogenetic alterations during early development. The attenuation of
      bone morphogenetic protein (Bmp) signaling at the posterior primitive streak of
      embryos leads to the caudal dysmorphogenesis including the cloaca and fusion of
      both hindlimbs. Genetic tissue lineage studies indicate the presence of
      coordinated organogenesis. Hedgehog (HH)-responding cells derived from peri
      cloacal mesenchyme (PCM) contribute to the urogenital/reproductive organs. These
      findings indicate the existence of developmental programs for the coordinated
      organogenesis of urogenital/reproductive tissues based on growth factor function
      and crosstalk.

PMID- 19765974
TI  - The role of CNS glia in preserving axon function.
AB  - Axons are the physical conduits by which information is relayed within the
      nervous system and as such, are essential for normal neurological function. In
      the central nervous system (CNS), axons comprise the bulk of the white matter,
      where they are closely associated with glial cells. Primary alterations of glial
      cell functions can have detrimental secondary consequences for axons,
      demonstrating that white matter glia are important custodians of axonal
      integrity. For example, genetic ablation of key oligodendroglial molecules
      abrogates the oligodendrocytes' supportive function, while expression of mutant
      super oxide dismutase in astrocytes expedites progression of motor neuron
      disease. Here we review some of the recent literature on the role of CNS glia in
      axonal health.

PMID- 19765975
TI  - Stability effects of mutations and protein evolvability.
AB  - The past several years have seen novel insights at the interface of protein
      biophysics and evolution. The accepted paradigm that proteins can tolerate nearly
      any amino acid substitution has been replaced by the view that the deleterious
      effects of mutations, and especially their tendency to undermine the
      thermodynamic and kinetic stability of protein, is a major constraint on protein
      evolvability--the ability of proteins to acquire changes in sequence and
      function. We summarize recent findings regarding how mutations affect protein
      stability, and how stability affects protein evolution. We describe ways of
      predicting and analyzing stability effects of mutations, and mechanisms that
      buffer or compensate for these destabilizing effects and thereby promote protein
      evolvabilty, in nature and in the laboratory.

PMID- 19765976
TI  - High-throughput crystallography for structural genomics.
AB  - Protein X-ray crystallography recently celebrated its 50th anniversary. The
      structures of myoglobin and hemoglobin determined by Kendrew and Perutz provided
      the first glimpses into the complex protein architecture and chemistry. Since
      then, the field of structural molecular biology has experienced extraordinary
      progress and now more than 55000 protein structures have been deposited into the
      Protein Data Bank. In the past decade many advances in macromolecular
      crystallography have been driven by world-wide structural genomics efforts. This
      was made possible because of third-generation synchrotron sources, structure
      phasing approaches using anomalous signal, and cryo-crystallography.
      Complementary progress in molecular biology, proteomics, hardware and software
      for crystallographic data collection, structure determination and refinement,
      computer science, databases, robotics and automation improved and accelerated
      many processes. These advancements provide the robust foundation for structural
      molecular biology and assure strong contribution to science in the future. In
      this report we focus mainly on reviewing structural genomics high-throughput X
      ray crystallography technologies and their impact.

PMID- 19765977
TI  - The importance of early symptom recognition in the context of early detection and
      cancer survival.
AB  - Since there is evidence that stage is an important prognostic factor in cancer,
      interventions aimed at 'down-staging' are part of a comprehensive cancer control
      approach. Besides organised screening programmes, raising awareness of detectable
      signs and symptoms is recommended. A precise definition of early cancer signs and
      symptoms, however, is lacking and there has also been no systematic review
      regarding the impact of awareness raising interventions on cancer outcomes. We
      reviewed the scientific medical literature to assess the consistency and
      availability of a definition for early cancer symptoms as well as to assess the
      impact of early cancer diagnosis on survival. Although early diagnosis is an
      important factor for cancer survival, other considerations such as the cancer
      profile of a country, the characteristics of cancer types and the availability of
      devices for diagnosis should be taken into account in promoting early cancer
      detection. There is a clear need for research to categorize cancer types
      according to early symptoms in order to increase comparability of studies in this
      field and to provide guidance for health personnel in primary care settings in
      low income regions.

PMID- 19765978
TI  - Clinical and psychometric validation of the EORTC QLQ-CR29 questionnaire module
      to assess health-related quality of life in patients with colorectal cancer.
AB  - This international study aimed to test the measurement properties of the updated
      European Organisation for Research and Treatment of Cancer (EORTC) questionnaire
      module for colorectal cancer, the QLQ-CR29. The QLQ-CR29 was administered with
      the QLQ-C30, core questionnaire, to 351 patients from seven countries.
      Questionnaire scaling and reliability were established and clinical and
      psychometric validity examined. Patient acceptability and understanding were
      assessed with a debriefing questionnaire. Multi-trait scaling analyses and face
      validity refined the module to four scales assessing urinary frequency, faecal
      seepage, stool consistency and body image and single items assessing other common
      problems following treatment for colorectal cancer. Scales distinguished between
      clinically distinct groups of patients and did not correlate with QLQ-C30 scales,
      demonstrating construct validity. The QLQ-CR29 scores were reproducible over time
      in stable health. The EORTC QLQ-CR29 demonstrates sufficient validity and
      reliability to support its use to supplement the EORTC QLQ-C30 to assess patient
      reported outcomes during treatment for colorectal cancer in clinical trials and
      other settings.

PMID- 19765979
TI  - Application of food industry waste to agricultural soils mitigates green house
      gas emissions.
AB  - Application of organic waste materials such as food processing and serving
      industry cooking oil waste (OFW) can recycle soil nitrate nitrogen (NO(3)-N),
      which is otherwise prone to leaching after the harvest of crop. Nitrogen (N)
      recycling will not only reduce the amount of N fertilizer application for corn
      crop production but is also expected to mitigate green house gas (GHG) emissions
      by saving energy to be used for the production of the same amount of industrial
      fertilizer N required for the growth of corn crop. Application of OFW at 10Mg
      solid ha(-1)y(-1) conserved 68 kg N ha(-1)y(-1) which ultimately saved 134 L
      diesel ha(-1)y(-1), which would otherwise be used for the production of
      fertilizer N as urea. Average fossil energy substitution value (FESV) of N
      conserved/recycled was calculated to be 93 US$ ha(-1)y(-1), which is about 13
      million US$y(-1). Potential amount of GHG mitigation through the application of
      OFW to agricultural soils in Canada is estimated to be 57 Gg CO(2)Eq y(-1).

PMID- 19765980
TI  - Toxicity of some glucose/mannose-binding lectins to Biomphalaria glabrata and
      Artemia salina.
AB  - Schistosomiasis or bilharzia, which affects millions of people living in Africa,
      Asia and Latin America, is closely associated with certain species of aquatic
      snails. One way of attacking the disease is to eradicate the host snails.
      Molluscicidal activities of natural compounds are especially important in the
      widespread control of this tropical disease. As part of our search for natural
      compounds with molluscicidal properties for the vector control of
      schistosomiasis, we are now evaluating for the first time the toxicity of the
      plant lectins from Canavalia brasiliensis (ConBr), Cratylia floribunda (CFL),
      Dioclea guianensis (Dgui), Dioclea grandiflora (DGL) and Dioclea virgata (Dvir)
      to Biomphalaria glabrata Say and Artemia salina Leach. Results indicate that all
      the samples were toxic to A. salina Leach, some of them with values of lethal
      concentration that kills 90% of the population (LC(90))<10 microg mL(-1). They
      are also active against B. glabrata Say, killing 100% of adult snails, at a
      concentration of 50 microg mL(-1). The lectins CFL and Dgui possess properties
      lethal to mollusks, with values of LC(90)=50.3 microg mL(-1) and LC(90)=41.0
      microg mL(-1), respectively.

PMID- 19765981
TI  - Evaluation of pretreatment methods on mixed inoculum for both batch and
      continuous thermophilic biohydrogen production from cassava stillage.
AB  - Anaerobic sludges, pretreated by chloroform, base, acid, heat and loading-shock,
      as well as untreated sludge were evaluated for their thermophilic fermentative
      hydrogen-producing characters from cassava stillage in both batch and continuous
      experiments. Results showed that the highest hydrogen production was obtained by
      untreated sludge and there were significant differences (p<0.05) in hydrogen
      yields (varied from 32.9 to 65.3mlH(2)/gVS) among the tested pretreatment methods
      in batch experiments. However, the differences in hydrogen yields disappeared in
      continuous experiments, which indicated the pretreatment methods had only short
      term effects on the hydrogen production. Further study showed that alkalinity was
      a crucial parameter influencing the fermentation process. When the influent was
      adjusted to pH 6 by NaHCO(3) instead of NaOH, the hydrogen yield increased from
      about 40 to 52mlH(2)/gVS in all the experiments. Therefore, pretreatment of
      anaerobic sludge is unnecessary for practical thermophilic fermentative hydrogen
      production from cassava stillage.

PMID- 19765982
TI  - The second Renewable Energy 2008 International Conference.

PMID- 19765983
TI  - A dioxygenase of Pleurotus sapidus transforms (+)-valencene regio-specifically to
      (+)-nootkatone via a stereo-specific allylic hydroperoxidation.
AB  - A selective and highly efficient allylic oxidation of the sesquiterpene (+)
      valencene to the grapefruit flavour compound (+)-nootkatone was achieved with
      lyophilisate of the edible mushroom Pleurotus sapidus. The catalytic reaction
      sequence was elucidated through the identification of intermediate, (+)-valencene
      derived hydroperoxides. A specific staining of hydroperoxides allowed the semi
      preparative isolation of two secondary (+)-valencene hydroperoxides, 6(R)
      Isopropenyl-4(R),4a(S)-dimethyl-2,3,4,4a,5,6,7,8-octahydro-naphthalen-4(S)-yl
      hydroperoxide and 6(R)-Isopropenyl-4(R),4a(S)-dimethyl-2,3,4,4a,5,6,7,8-octahydro
      naphthalen-2(R)-yl-hydroperoxide. Chemical reduction of the biotransformation
      products yielded a tertiary alcohol identified as 2(R)-Isopropenyl-8(R),8a(S)
      dimethyl-1,3,4,7,8,8a-hexahydro-2H-naphthalen-4a(R)-ol. This suggested a
      lipoxygenase-type oxidation of (+)-valencene via secondary and tertiary
      hydroperoxides and confirmed homology data of the key enzyme obtained previously
      from amino acid sequencing.

PMID- 19765984
TI  - Influence of trace elements on methane formation from a synthetic model substrate
      for maize silage.
AB  - The effect of a well-defined trace element solution and the elements nickel,
      cobalt and molybdenum on anaerobic digestion of a synthetic model substrate for
      maize silage was studied in batch reactor experiments at 35 degrees C. The
      defined substrate (dS) consisted of xylan and starch as the main carbon source,
      urea as nitrogen source and phosphorus from a 0.1M potassium phosphate buffer.
      Batch reactors were operated for 30 days with 1.5% organic dry matter (ODM) of
      inoculum sludge from a mono-maize biogas plant and 1% ODM of the defined
      substrate. Results showed an increase of methane yield of up to 30% upon addition
      of the trace element solution. With an addition of nickel at 10.6 microM, a final
      yield of 407 l kg(-1) ODM was reached and an enhanced methane production by 25%
      at day 25 of operation was observed. Total elimination of nickel from the trace
      element solution highly decreased methane formation and process stability. Cobalt
      in a concentration range of 0.4 up to 2.0 microM increased the methane production
      by 10% approximately. Interestingly, addition of molybdenum did not significantly
      effect methane production.

PMID- 19765985
TI  - Production of polyhydroxybutyrate by activated sludge performing enhanced
      biological phosphorus removal.
AB  - In this study, polyhydroxybutyrate (PHB)--a biodegradable plastics material--was
      produced by activated sludge performing enhanced biological phosphorus removal
      (EBPR) in batch experiments under anaerobic, aerobic and anaerobic/aerobic
      conditions. Under anaerobic conditions, the maximum PHB content of the dry
      biomass was 28.8% by weight, while under aerobic or anaerobic/aerobic conditions,
      the maximum PHB content was about 50%. The PHB production rate with respect to
      the volatile suspended solids (VSS) was: (i) 70 mg/(g VSS)h under aerobic
      conditions that followed anaerobic conditions, (ii) 156 mg/(g VSS)h under
      anaerobic condition, and (iii) 200mg/(g VSS)h under aerobic conditions with
      energy also supplied from polyphosphate. A side stream, with initially anaerobic
      conditions for PHB accumulation and phosphorus release, and then aerobic
      conditions for PHB accumulation, was proposed. In this side stream, biomass with
      a high PHB content and a high PHB production rate could be both achieved.

PMID- 19765986
TI  - Structure based design of novel irreversible FAAH inhibitors.
AB  - Fatty acid amide hydrolase (FAAH) has attracted significant attention due to its
      promise as an analgesic target. This has resulted in the discovery of numerous
      chemical classes as inhibitors of this potential therapeutic target. In this
      paper we disclose a new series of novel FAAH irreversible azetidine urea
      inhibitors. In general these compounds illustrate potent activity against the rat
      FAAH enzyme. Our SAR studies allowed us to optimize this series resulting in the
      identification of compounds 13 which were potent inhibitors of both human and rat
      enzyme. This series of compounds illustrated good hydrolase selectivity along
      with good PK properties.

PMID- 19765987
TI  - A Drosophila gustatory receptor essential for aversive taste and inhibiting male
      to-male courtship.
AB  - Contact chemosensation is required for several behaviors that promote insect
      survival. These include evasive behaviors such as suppression of feeding on
      repellent compounds, known as antifeedants, and inhibition of male-to-male
      courtship. However, the gustatory receptors (GRs) required for responding to
      nonvolatile avoidance chemicals are largely unknown. Exceptions include
      Drosophila GR66a and GR93a, which are required to prevent ingestion of caffeine,
      and GR32a, which is necessary for inhibiting male-to-male courtship. However,
      GR32a is dispensable for normal taste. Thus, distinct GRs may function in sensing
      avoidance pheromones and antifeedants. Here, we describe the requirements for
      GR33a, which is expressed widely in gustatory receptor neurons (GRNs) that
      respond to aversive chemicals. Gr33a mutant flies were impaired in avoiding all
      nonvolatile repellents tested, ranging from quinine to denatonium, lobeline, and
      caffeine. Gr33a mutant males also displayed increased male-to-male courtship,
      implying that it functioned in the detection of a repulsive male pheromone. In
      contrast to the broadly required olfactory receptor (OR) OR83b, which is
      essential for trafficking other ORs, GR66a and GR93a are localized normally in
      Gr33a mutant GRNs. Thus, rather than regulating GR trafficking, GR33a may be a
      coreceptor required for sensing all nonvolatile repulsive chemicals, including
      tastants and pheromones.

PMID- 19765988
TI  - Cell-cycle control by physiological matrix elasticity and in vivo tissue
      stiffening.
AB  - BACKGROUND: A number of adhesion-mediated signaling pathways and cell-cycle
      events have been identified that regulate cell proliferation, yet studies to date
      have been unable to determine which of these pathways control mitogenesis in
      response to physiologically relevant changes in tissue elasticity. In this
      report, we use hydrogel-based substrata matched to biological tissue stiffness to
      investigate the effects of matrix elasticity on the cell cycle. RESULTS: We find
      that physiological tissue stiffness acts as a cell-cycle inhibitor in mammary
      epithelial cells and vascular smooth muscle cells; subcellular analysis in these
      cells, mouse embryonic fibroblasts, and osteoblasts shows that cell-cycle control
      by matrix stiffness is widely conserved. Remarkably, most mitogenic events
      previously documented as extracellular matrix (ECM)/integrin-dependent proceed
      normally when matrix stiffness is altered in the range that controls mitogenesis.
      These include ERK activity, immediate-early gene expression, and cdk inhibitor
      expression. In contrast, FAK-dependent Rac activation, Rac-dependent cyclin D1
      gene induction, and cyclin D1-dependent Rb phosphorylation are strongly inhibited
      at physiological tissue stiffness and rescued when the matrix is stiffened in
      vitro. Importantly, the combined use of atomic force microscopy and fluorescence
      imaging in mice shows that comparable increases in tissue stiffness occur at
      sites of cell proliferation in vivo. CONCLUSIONS: Matrix remodeling associated
      with pathogenesis is in itself a positive regulator of the cell cycle through a
      highly selective effect on integrin-dependent signaling to FAK, Rac, and cyclin
      D1.

PMID- 19765989
TI  - Fpr3 and Zip3 ensure that initiation of meiotic recombination precedes chromosome
      synapsis in budding yeast.
AB  - BACKGROUND: Homolog pairing, synaptonemal complex (SC) assembly (chromosome
      synapsis), and crossover recombination are essential for successful meiotic
      chromosome segregation. A distinguishing feature of meiosis in budding yeast and
      mammals is that synapsis between homologs depends upon recombination; however,
      the molecular basis for this contingency is not understood. RESULTS: We show here
      that the yeast proline isomerase Fpr3 and the small ubiquitin-like modifier
      (SUMO) ligase Zip3 ensure that SC assembly is dependent upon recombination
      initiation. When Fpr3 and Zip3 are absent, synapsis occurs even in a mutant that
      fails to initiate recombination and homolog pairing. Fpr3 and Zip3 appear to
      specifically prevent synapsis initiation at centromeric sites. This result is
      consistent with previous observations of SC proteins localizing to centromeres
      prior to and independent of meiotic recombination initiation. Finally, we show
      that without Fpr3 and Zip3 activities, the synapsis initiation components Zip2
      and Zip4 are dispensable for chromosome synapsis. CONCLUSIONS: Fpr3 and Zip3
      represent parallel pathways that function in a checkpoint-like manner to ensure
      that chromosome synapsis is contingent on the initiation of recombination. We
      propose that, during normal meiosis, Zip2 and Zip4 act downstream of
      recombination signals to oppose Fpr3- and Zip3-mediated inhibitions to initiating
      SC assembly at centromeres. These data suggest a role for centromeres in
      coordinating major meiotic chromosomal events and draw an interesting parallel
      between yeast centromeres and C. elegans pairing centers.

PMID- 19765990
TI  - Negative effects of an introduced bird species on growth and survival in a native
      bird community.
AB  - Exploitative competition is a major determinant of community structure in natural
      assemblages [1, 2], but, introduced species are rarely competitors that lead to
      extinction of native species [3, 4]. Here we document strong community-wide
      competition from the Japanese white-eye (Zosterops japonicus) on native Hawaiian
      passerine birds. Introduced in 1929 [5], white-eye successfully invaded old
      growth forest and coexisted with eight native species [6], overlapping multiple
      foraging substrates with each but evidencing no agonistic interactions [7]. The
      endangered Hawaii akepa (Loxops coccineus coccineus) was viable during 1987-1999
      but became nonviable during 2000-2006 in association with an abrupt increase in
      white-eyes [7]. We show that after 2000, juveniles of every native bird species
      measured had lower mass and shorter bills and tarsi. For most species, lower mass
      led to decreased juvenile survival, and shorter bills to decreased survival of
      second-year and older adults. Lower survival of smaller birds represents
      normalizing selection that is restoring previous size means to future generations
      [8]. Birds at a nearby site with fewer white-eyes had normal size. White-eye had
      less stunting of bills and did not suffer the survival consequences of native
      species. Exploitative competition for food between native birds and an introduced
      species requires intensive management to prevent further declines.

PMID- 19765991
TI  - Ribosome-free terminals of rough ER allow formation of STIM1 puncta and
      segregation of STIM1 from IP(3) receptors.
AB  - Store-operated Ca(2+) entry is a ubiquitous mechanism that prevents the depletion
      of endoplasmic reticulum (ER) calcium. A reduction of ER calcium triggers
      translocation of STIM proteins, which serve as calcium sensors in the ER, to
      subplasmalemmal puncta where they interact with and activate Orai channels. In
      pancreatic acinar cells, inositol 1,4,5-trisphosphate (IP(3)) receptors populate
      the apical part of the ER. Here, however, we observe that STIM1 translocates
      exclusively to the lateral and basal regions following ER Ca(2+) loss. This
      finding is paradoxical because the basal and lateral regions of the acinar cells
      contain rough ER (RER); the size of the ribosomes that decorate RER is larger
      than the distance that can be spanned by a STIM-Orai complex, and STIM1 function
      should therefore not be possible. We resolve this paradox and characterize
      ribosome-free terminals of the RER that form junctions between the reticulum and
      the plasma membrane in the basal and lateral regions of the acinar cells. Our
      findings indicate that different ER compartments specialize in different calcium
      handling functions (Ca(2+) release and Ca(2+) reloading) and that any potential
      interference between Ca(2+) release and Ca(2+) influx is minimized by the spatial
      separation of the two processes.

PMID- 19765992
TI  - Tgfbeta signal inhibition cooperates in the induction of iPSCs and replaces Sox2
      and cMyc.
AB  - Ectopic expression of Oct4, Sox2, cMyc, and Klf4 confers a pluripotent state upon
      several differentiated cell types, generating induced pluripotent stem cells
      (iPSCs) [1-8]. iPSC derivation is highly inefficient, and the underlying
      mechanisms are largely unknown. This low efficiency suggests the existence of
      additional cooperative factors whose identification is critical for understanding
      reprogramming. In addition, the therapeutic use of iPSCs relies on the
      development of efficient nongenetic means of factor delivery, and although a
      handful of replacement molecules have been identified, their use yields a further
      reduction to the already low reprogramming efficiency [9-11]. Thus, the
      identification of compounds that enhance rather than solely replace the function
      of the reprogramming factors will be of great use. Here, we demonstrate that
      inhibition of Tgfbbeta signaling cooperates in the reprogramming of murine
      fibroblasts by enabling faster, more efficient induction of iPSCs, whereas
      activation of Tgfbeta signaling blocks reprogramming. In addition to exhibiting a
      strong cooperative effect, the Tgfbeta receptor inhibitor bypasses the
      requirement for exogenous cMyc or Sox2, highlighting its dual role as a
      cooperative and replacement factor. The identification of a highly characterized
      pathway operating in iPSC induction will open new avenues for mechanistic
      dissection of the reprogramming process.

PMID- 19765993
TI  - Nonsomatotopic organization of the higher motor centers in octopus.
AB  - Hyperredundant limbs with a virtually unlimited number of degrees of freedom
      (DOFs) pose a challenge for both biological and computational systems of motor
      control. In the flexible arms of the octopus, simplification strategies have
      evolved to reduce the number of controlled DOFs. Motor control in the octopus
      nervous system is hierarchically organized. A relatively small central brain
      integrates a huge amount of visual and tactile information from the large optic
      lobes and the peripheral nervous system of the arms and issues commands to lower
      motor centers controlling the elaborated neuromuscular system of the arms. This
      unique organization raises new questions on the organization of the octopus brain
      and whether and how it represents the rich movement repertoire. We developed a
      method of brain microstimulation in freely behaving animals and stimulated the
      higher motor centers-the basal lobes-thus inducing discrete and complex sets of
      movements. As stimulation strength increased, complex movements were recruited
      from basic components shared by different types of movement. We found no
      stimulation site where movements of a single arm or body part could be elicited.
      Discrete and complex components have no central topographical organization but
      are distributed over wide regions.

PMID- 19765994
TI  - STIM1 is a calcium sensor specialized for digital signaling.
AB  - When cells are activated by calcium-mobilizing agonists at low, physiological
      concentrations, the resulting calcium signals generally take the form of
      repetitive regenerative discharges of stored calcium, termed calcium oscillations
      [1]. These intracellular calcium oscillations have long fascinated biologists as
      a mode of digitized intracellular signaling. Recent work has highlighted the role
      of calcium influx as an essential component of calcium oscillations [2]. This
      influx occurs through a process known as store-operated calcium entry, which is
      initiated by calcium sensor proteins, STIM1 and STIM2, in the endoplasmic
      reticulum [3]. STIM2 is activated by changes in endoplasmic reticulum calcium
      near the resting level, whereas a threshold of calcium depletion is required for
      STIM1 activation [4]. Here we show that, surprisingly, it is STIM1 and not STIM2
      that is exclusively involved in calcium entry during calcium oscillations. The
      implication is that each oscillation produces a transient drop in endoplasmic
      reticulum calcium and that this drop is sufficient to transiently activate STIM1.
      This transient activation of STIM1 can be observed in some cells by total
      internal reflection fluorescence microscopy. This arrangement nicely provides a
      clearly defined and unambiguous signaling system, translating a digital calcium
      release signal into calcium influx that can signal to downstream effectors.

PMID- 19765995
TI  - Effect of shoe type on plantar pressure: a gender comparison.
AB  - Despite the differences in materials, racing flats have begun to be used not only
      for racing, but also for daily training. As there are data suggesting a gender
      difference in overuse injuries in runners, shoe choice may affect loading
      patterns during running. The purpose was to determine differences in plantar
      pressure between genders when running in training shoes and racing flats. In-shoe
      plantar pressure data were collected from 34 subjects (17m, 17f) who ran over
      ground in both a racing flat and training shoe. Contact area (CA), maximum force
      (MF), and contact time under the entire foot and beneath eight foot regions were
      collected. Each variable was analyzed using a shoe by gender repeated measures
      ANOVA (alpha=0.05). In men, MF was increased in the racing flats (p=0.016)
      beneath the medial midfoot (MMF), yet was increased beneath the medial forefoot
      (MFF) in the training shoe (p=0.018). Independent of gender, CA was decreased in
      the racing flats beneath the entire foot (p=0.029), the MMF (p=0.013), and the
      MFF (p=0.030), and increased beneath the lateral forefoot (LFF) (p=0.023). In the
      racing flats, MF was increased beneath the entire foot (p<0.001) and the LFF
      (p<0.001). Independent of the shoe, CA was decreased in men beneath the MFF
      (p=0.007) and middle forefoot (p<0.001), while MF was increased in the LFF
      (p=0.002). The LFF is an area of increased stress fracture risk in men. Based on
      the gender differences in loading, running shoe design should be gender specific
      in an attempt to prevent injuries.

PMID- 19765996
TI  - Turning behavior in healthy older adults: Is there a preference for step versus
      spin turns?
AB  - This research examined the prevalence of step turns and spin turns during turning
      while walking in healthy older adults. The potential effect of magnitude of the
      turn and walking velocity on the prevalence of the step and spin turns were also
      investigated by examining the participants' performance as they made 45 degrees
      and 90 degrees turns while walking at three different velocities. Results showed
      that healthy older adults in our study preferred spin turns while walking either
      slower or faster than their natural walking speed. Only during 90 degrees turns
      while walking fast the participants showed a preference for step turns over spin
      turns. Spin turns are less stable and have a greater biomechanical cost than step
      turns. The high incidence of spin turns in older adults may contribute to the
      higher risk of falling in this population.

PMID- 19765997
TI  - Bacteriophages as model organisms for virus emergence research.
AB  - Viruses fully emerge by gaining the ability to sustainably infect new host
      populations. When the hosts are humans, emerging viruses can present major public
      health issues, as exemplified by the AIDS pandemic. Therefore, heuristic
      approaches to identify nascent diseases before they become pandemic would be
      valuable. Unfortunately, the current patient-based and epidemiological approaches
      are ill-suited in this regard because they are largely responsive and not
      predictive. Alternative approaches based on virus evolutionary ecology might have
      greater potential to predict virus emergence. However, given the difficulties
      encountered when studying metazoan viruses in this context, the development of
      new model systems is greatly desirable. Here, I highlight studies that show that
      bacteriophages are appropriate model organisms for virus emergence research
      because of the ease in which important population parameters can be manipulated.
      Ideally this research will permit identifying major factors determining the
      persistence or extinction of emerging viruses. If such viruses could be
      recognized in advance, patient-based and epidemiological strategies could be
      better mobilized to deal with them.

PMID- 19765999
TI  - Are essential genes really essential?
AB  - Gene essentiality has emerged as an often-asked question in the wake of bacterial
      genome sequencing and a renaissance in studies of prokaryotic physiology. Genome
      scale efforts at describing essential gene sets have necessarily been carried out
      under standard and tractable growth conditions in a laboratory setting. In
      addition to reinforcing our understanding of core bacterial physiology, these
      studies have also uncovered large numbers of essential genes encoding proteins
      whose functions remain poorly described. Studies of these and other elements of
      core physiology have naturally followed and several paradoxes, relating to growth
      conditions and genetic context, have begun to challenge our understanding of the
      term "essential gene". Most recently genome-scale genetic interaction studies
      have revealed remarkable density and redundancy in biological systems with
      profound implications for dispensability phenotypes associated with single gene
      mutations. Consequently, the phenotype "essential" should be carefully viewed as
      contextual.

PMID- 19765998
TI  - Killing me softly: chlamydial use of proteolysis for evading host defenses.
AB  - Chlamydial infections in humans cause severe health problems, including blinding
      trachoma and sexually transmitted diseases. Although the involved pathogenic
      mechanisms remain unclear, the ability to replicate and maintain long-term
      residence in the infected cells seems to significantly contribute to chlamydial
      pathogenicity. These obligate intracellular parasites maintain a delicate balance
      between exploiting and protecting their host: they occupy intracellular space and
      acquire nutrients from the infected cells, but at the same time they have to
      maintain the integrity of the host cells for the completion of their
      intracellular growth. For this purpose, chlamydiae hijack certain signaling
      pathways that prevent the host cells from undergoing apoptosis induced by
      intracellular stress and protect the infected cells from recognition and attack
      by host defenses. Interestingly, one of the strategies that chlamydiae use for
      these purposes is the induction of limited proteolysis of host proteins, which is
      the main focus of this article.

PMID- 19766000
TI  - Exploring the inner membrane proteome of Escherichia coli: which proteins are
      eluding detection and why?
AB  - Proteins embedded in membranes are important for helping the cell adapt to
      changes in the extracellular milieu and often play key roles in the life cycles
      of pathogenic microbes. Bioinformatic predictions can provide an estimate of
      membrane proteins, but experimental approaches of detection are required for a
      deeper understanding of their functions. To determine the effectiveness of
      experimental detection approaches, here we collate and discuss data from
      available proteomic analyses on the inner (or cytoplasmic) membrane of
      Escherichia coli. We compile a list of proteins that have been experimentally
      detected and by comparing this to a predicted proteome we identify membrane
      proteins that have eluded us experimentally. Limitations of current proteomic
      analyses together with possible solutions are discussed. We also provide a list
      of proteins for benchmarking the performance of future proteomic studies.

PMID- 19766001
TI  - Pilomyxoid astrocytoma with involvement of the sella turcica in an adolescent.
AB  - Pilomyxoid astrocytoma (PMA) is a recently described tumor typically occurring in
      the hypothalamic-chiasmatic region of very young children. PMA is characterized
      by a more aggressive course than pilocytic astrocytoma and exhibits certain
      differing histological features. We report a PMA in an adolescent patient with
      visual field disturbance. Imaging studies revealed enlargement of the sella
      turcica due to a homogenously enhancing sellar and suprasellar mass identifiable
      both on CT scans and MRI. We believe that PMA may be included in the list of
      differential diagnoses of the lesions expanding the sella turcica.

PMID- 19766002
TI  - Secondary abscess arising in a craniopharyngioma.
AB  - An abscess arising in a craniopharyngioma is rare, but has potentially high
      mortality and morbidity. Diagnosis is difficult because clinical and
      neuroradiological characteristics are not clearly defined. We report a patient
      with a pituitary abscess concomitant with a craniopharyngioma and discuss the
      pathophysiological mechanism. We discuss the previous five reports and suggest
      that abscesses with craniopharyngioma remain challenging clinical entities. We
      speculate that inflammation is a response to components of the ruptured
      epithelium of the cyst, thereby providing an explanation of the mechanism of
      abscess formation.

PMID- 19766003
TI  - Kernohan-Woltman notch phenomenon caused by an acute subdural hematoma.
AB  - Uncal herniation through the tentorial notch is occasionally associated with
      false localizing ipsilateral hemiparesis, known as the Kernohan-Woltman notch
      phenomenon (KWNP). We report an 81-year-old female who presented with a decreased
      level of consciousness, a right mydriasis and an ipsilateral motor deficit caused
      by a large right hemispheric subdural hematoma that was immediately evacuated.
      The patient recovered well, although her right hemiplegia persisted. A follow-up
      MRI showed a residual lesion in the left cerebral peduncle, corresponding to
      KWNP. The presence of such a structural lesion suggests a poor prognosis for
      recovery from the initial motor deficit.

PMID- 19766004
TI  - Intraneural perineurioma.
AB  - Intraneural perineurioma is a rare tumour that affects peripheral nerves and,
      based on its histological features, may be confused with hereditary motor and
      sensory neuropathies. Detailed neuropathology, including immunoperoxidase stains
      and electron microscopy, is vital to distinguish these conditions. We report two
      patients with intraneural perineurioma that demonstrate salient features of this
      tumour. The first patient is the longest reported follow-up of an intraneural
      perineurioma; extension of the lesion was observed over 14years. The second
      patient is an 11-year-old female whose treatment highlights some of the
      controversy surrounding the management of these lesions, and the importance of
      thorough macroscopic and microscopic assessment by pathologists, including the
      status of surgical resection margins.

PMID- 19766005
TI  - Malignant fibrous histiocytosis after high-dose proton radiation therapy for
      anaplastic astrocytoma.
AB  - This report presents a 70-year-old male who presented with a rare malignant
      fibrous histiocytosis after high-dose proton radiation therapy for anaplastic
      astrocytoma. To our knowledge, malignant fibrous histiocytosis caused by proton
      therapy has not been reported, therefore the clinical features of this
      complication are described and previous cases are reviewed.

PMID- 19766006
TI  - Glioblastoma multiforme fades on CT imaging after dexamethasone therapy.
AB  - We describe a patient in whom an enhancing lesion seen on CT scan faded following
      dexamethasone therapy. Subsequent biopsy revealed a glioblastoma multiforme.
      Various intrinsic cerebral lesions have been noted to disappear on CT imaging
      after the administration of corticosteroids, but it is less common for gliomas to
      exhibit this property.

PMID- 19766007
TI  - Axonal effects of camphor poisoning.
AB  - This report documents changes to axonal excitability in motor nerves in acute
      camphor toxicity. Although there were no changes to indicate an alteration in
      resting membrane potential, there was an exaggerated response to hyperpolarising
      currents in both threshold electrotonus and the current-threshold relationship.
      These findings suggest a transient decrease in the hyperpolarisation-activated
      conductance (I(H)). This report demonstrates that recently developed techniques
      for measuring axonal excitability are readily applied in the acute care setting
      and can document subclinical abnormalities that could be relevant to the
      underlying pathophysiology.

PMID- 19766008
TI  - Skull osteohypertrophy as a complication of bone wax.
AB  - A 51-year-old woman with bone wax-induced osteohypertrophy presented with
      exophthalmos 9 years after a craniotomy for a right internal carotid bifurcation
      aneurysm. CT scans revealed thickening of the frontotemporal bone flap and
      surrounding bone, thickening of the upper and lateral orbital walls, and a
      limited intraorbital cavity. Intraoperative findings revealed residual bone wax
      under the bone flap, grayish-white discoloration of the flap, and degeneration of
      the temporal muscle. Pathological examination revealed granulation and
      osteogenesis due to a foreign body. To our knowledge, this is the first report of
      bone wax-induced hyperostosis leading to exophthalmos.

PMID- 19766009
TI  - Breast carcinoma metastasis to intracranial meningioma.
AB  - Meningiomas and breast cancers are common tumors among women in the fifth to
      seventh decade. However, metastasis from breast cancer to an intracranial
      meningioma is rare. A 63-year-old woman presented with headache, nausea and
      vomiting, and progressive right hemiparesis for one month. She had undergone a
      right modified radical mastectomy in another hospital 10 years prior. At that
      time, the pathological diagnosis was infiltrating ductal carcinoma. She required
      adjuvant radiotherapy and chemotherapy for a local recurrence 7 years later. On
      admission to our hospital, cranial CT scans showed a brightly enhancing,
      irregularly shaped lesion over the left high parietal lobe with surrounding
      parenchymal edema. Histopathological examination of the lesion revealed two
      distinct tumor types, meningioma and metastatic carcinoma of breast tissue
      origin. Although meningiomas have well-known radiological features, other tumors,
      including metastases from breast cancers may simulate them. In the clinical
      setting of previously diagnosed breast cancer, prompt craniotomy for removal of
      meningioma-like intracranial lesions is recommended to avoid missing the
      diagnosis of breast cancer metastasis which carries a poorer prognosis than
      meningioma and requires a different treatment strategy.

PMID- 19766010
TI  - PET-compatible endothelin receptor radioligands: synthesis and first in vitro and
      in vivo studies.
AB  - The expression and function of endothelin (ET) receptors is abnormal in
      cardiovascular diseases, tumor progression, and tumor metastasis. In this study,
      we prepared two [(18)F]-fluorinated derivatives of the non-peptide ET(A) receptor
      antagonist PD 156707 and evaluated their ET receptor binding potencies. Ex vivo
      as well as in vivo biodistribution studies in mice were performed, as well as the
      metabolism of the radiotracer, which was examined by metabolite analysis in mice
      and rats. All tested derivatives of PD 156707 exhibited potent in vitro
      pharmacological characteristics with K(i) values comparable to that of the lead
      compound. The biodistribution studies showed a high accumulation of the tracer in
      bile and intestine. In vivo we were able to show that the visualization of the
      heart as a major target organ with high ET(A)R expression is possible.

PMID- 19766011
TI  - Ultrastructural observation on genesis and morphology of cortical granules in
      Macrobrachium nipponense (Crustacea, Caridea).
AB  - Cortical granules are secretory vesicles in oocytes that develop from the Golgi
      complex. In the freshwater shrimp, Macrobrachium nipponense, mitochondria
      participates in the formation of cortical granules. We investigated the
      structural changes of mitochondria and the distribution cortical granules in
      different stages of oocyte development. Transmission electron microscopy provided
      evidence for the involvement of mitochondria and a particular spiral lamellar
      organization and an electron-lucent area in internal cortical granules. The
      ooplasm provided material for the cortical granules in early oocyte development.
      We demonstrated that mitochondria play a role in coalescence and maturation of
      cortical granules in this species. Additionally, a concept of cortical granules
      regarded as a functional integration is put forward. The genesis of shrimp
      cortical granules exhibited a particular pathway of maturation. The outer shape
      and inner organization considering different taxa suggested general as well as
      specific features of the development of cortical granules.

PMID- 19766012
TI  - '2+1' Tricarbonyltechnetium(I) and -rhenium(I) mixed-ligand complexes with N
      methylpyridine-2-carboxyamide and isocyanide or imidazole ligands-potential
      precursors of radiopharmaceuticals.
AB  - Complexes of tricarbonyltechnetium(I)-99m and rhenium(I)-188, of '2+1' type: with
      N-methylpyridine-2-carboxyamide as a neutral bidentate ligand and either tert
      butyl 3-isocyanopropionate or imidazole as a monodentate ligand, have been
      obtained on n.c.a. level. The complexes exhibit moderate lipophilicity and rather
      high stability in neutral aqueous solutions. The latter has been evidenced from
      the tests on histidine/cysteine challenge and on protein binding in rat serum.
      The rhenium complexes studied are much more stable than their technetium
      analogues. The isocyanopropionate complex may be considered promising model for
      radiopharmaceutical precursors.

PMID- 19766013
TI  - Overexpression of millet ZIP-like gene (SiPf40) affects lateral bud outgrowth in
      tobacco and millet.
AB  - A SiPf40 gene was identified from an immature seed cDNA library of foxtail millet
      (Setaria italica). This gene encodes for a 29.4 KDa protein containing eight
      potential transmembrane domains and a highly conserved ZIP signature motif
      typical of ZIPs (zinc or iron transporter proteins) family. Other SiPf40
      potential homologous genes have also been identified in rice, maize, wheat and
      Arabidopsis by Southern analysis. Expression data showed that this gene is
      preferentially expressed in millet hypocotyl and bud; however, a minimal level of
      constitutive expression could be detected in other foxtail millet tissues.
      Overexpression of SiPf40 gene causes extra branches in tobacco and extra
      tillering in millet associated with vessel enlarging and xylary fibers
      increasing, whereas the tiller number decreases in SiPf40 gene silenced plants.
      Moreover, IAA content decreased significantly in shoot apex of the transgenic
      tobacco overexpressing SiPf40 gene. All together, these morphological alterations
      indicate that SiPf40 gene is essential for lateral shoots growth.

PMID- 19766014
TI  - Surgical repair of pectus excavatum not requiring exogenous implants in 113
      patients.
AB  - OBJECTIVE: Pectus excavatum is relatively common congenital chest deformity that
      is often accompanied by physical and psychological impairment. The surgical
      methods for pectus excavatum repair are the subject of some controversy. We
      review our experience using a procedure in which the introduction of exogenous
      material is unnecessary. METHODS: From July 1993 to March 2008, 113 patients
      underwent surgical repair of pectus excavatum. Sterno-costal elevation was
      adopted for 102 patients, including all of the paediatric patients and most of
      the adults. Sternal turnover was employed for 11 adult patients with severe
      asymmetric deformities. In sterno-costal elevation, a section of the third or
      fourth to the seventh costal cartilages as well as the lower tip of the sternum
      below the sixth cartilage junction are resected, and all of the cartilage stumps
      are re-sutured to the sternum. The secured ribs generate 0.5-10 kg of tension,
      pulling the sternum bilaterally, such that the resultant force causes the sternum
      to rise anteriorly. These forces are sufficient to correct the deformities and to
      prevent flail chest. In sternal turnover, the sternum is cut at the third
      intercostal space. The lower part of the sternum is turned over and fixed to the
      upper sternum with an overlap of 1cm. Sections of the third to the seventh rib
      cartilages are resected and affixed in the same fashion as in sterno-costal
      elevation. RESULTS: There were no operative deaths, and in all cases the
      deformities were corrected satisfactorily. Ninety-nine patients (88%) were graded
      as Excellent, and the remaining 14 (12%) were graded Good. None of the patients
      developed any life-threatening complications. No patient reported residual pain.
      No re-operations were required for any reasons. The patients resumed daily
      activities of all types, including contact sports, within 3 months after surgery.
      CONCLUSIONS: We believe that morbidity is one of the most important factors to be
      considered in operative invasions. Our technique represents a less-invasive and
      lower-risk procedure for the repair of pectus excavatum in any age group.

PMID- 19766015
TI  - The brain, the spinal cord, selective antegrade cerebral perfusion and corporeal
      arrest temperature - are we reducing the margin of patient safety in aortic arch
      surgery?

PMID- 19766016
TI  - Low-income women's reproductive weight patterns empirically based clusters of
      prepregnant, gestational, and postpartum weights.
AB  - BACKGROUND: Women have varying weight responses to pregnancy and the postpartum
      period. The purpose of this study was to derive sub-groups of women based on
      differing reproductive weight clusters; to validate clusters by reference to
      adequacy of gestational weight gain (GWG) and postpartum incremental weight
      shifts; and to examine associations between clusters and demographic, behavioral,
      and psychosocial variables. METHOD: A cluster analysis was conducted of a multi
      ethnic/racial sample of low-income women (n = 247). Clusters were derived from
      three weight variables: prepregnant body mass index, GWG, and postpartum retained
      weight. RESULTS: Five clusters were derived: Cluster 1, normal weight-high
      prenatal gain-average retain; cluster 2, normal weight-low prenatal gain-zero
      retain; cluster 3, high normal weight-high prenatal gain-high retain; cluster 4,
      obese-low prenatal gain-average retain; and cluster 5, overweight-very high
      prenatal gain-very high retain. Clusters differed with regard to postpartum
      weight shifts (p < .001), with clusters 3, 4, and 5, mostly gaining weight
      between 6 weeks and 12 months postpartum, whereas clusters 1 and 2 were losing
      weight. Clusters were also associated with race/ethnicity (p < .01),
      breastfeeding immediately postdelivery (p < .01), smoking at 12 months (p < .05),
      and reaching weight goals at 6 and 12 months (p < .001), but not depressive
      symptoms, fat intake habits, or physical activity. CONCLUSION: In a five-cluster
      solution, postpartum weight shifts, ethnicity, and initial breastfeeding were
      among factors associated with clusters. Monitoring of weight and appropriate
      intervention beyond the 6 weeks after birth is needed for low-income women in
      high normal weight, overweight, and obese clusters.

PMID- 19766017
TI  - Chemical ablation of the gallbladder with acetic acid.
AB  - PURPOSE: Chemical ablation of the gallbladder may be a useful alternative to
      surgery for inoperable disease. The purpose of this study was to investigate the
      feasibility of chemical ablation of the gallbladder with acetic acid in a canine
      model. MATERIALS AND METHODS: Five beagle dogs underwent percutaneous
      transhepatic cholecystostomy. Percutaneous occlusion of the cystic duct was
      performed with use of n-butyl cyanoacrylate (NBCA) and coils. After confirmation
      of occlusion of the cystic duct, sclerotherapy of the gallbladder was performed
      with 4-7 mL of 50% acetic acid through the drainage catheter. Acetic acid was
      retained for 20 minutes with intermittent position change. The drainage catheter
      was removed immediately after sclerotherapy. The dogs were euthanized 8 weeks
      after the procedure. The gallbladders and adjacent organs were evaluated grossly
      as well as microscopically. RESULTS: All dogs survived without serious
      complications during the experimental period. Sclerotherapy was technically
      successful in all dogs. Gross specimens of the gallbladder showed shrinkage and
      fibrotic change without retention of any bile, mucus, or pus. Histologic
      examinations from the body and fundus of the gallbladder demonstrated complete
      ablation of the mucosa. However, the neck region of the gallbladder near the
      cystic duct, where NBCA and coils for cystic duct occlusion were located, had
      focal areas of remnant or regenerating mucosa. CONCLUSIONS: Chemical ablation of
      the gallbladder with 50% acetic acid was effective and safe. Complete ablation
      was achieved in the majority of gallbladder mucosa except for a small portion
      located in the gallbladder neck.

PMID- 19766018
TI  - Aspergilloma in a cavity formed after percutaneous radiofrequency ablation for
      lung cancer.

PMID- 19766019
TI  - Shoulder arthroplasty in the paraplegic patient.
AB  - INTRODUCTION: Shoulder arthroplasty in the paraplegic patient is a challenging
      procedure, because of the patients' unique demands on the shoulder. Previous
      information on the outcomes of this surgery in the literature is quite limited.
      Our experience in the prosthetic reconstruction of the arthritic shoulder in
      patients with pre-existing paraplegia was reviewed to define the results and
      identify any complications or the need for revision surgery. METHOD: Six patients
      were identified as eligible for inclusion. One patient had a humeral head
      replacement (HHR) and the remaining patients total shoulder arthroplasty (TSA).
      The average age at time of surgery was 68.7 years. The most common cause of the
      paraplegia was poliomyelitis, which was present in 3 patients. The other
      etiologies were transverse myelitis, spina bifida, and familial spastic
      paraparesis. Patients were followed for an average of 84 months, ranging from a
      minimum of 24 months up to 200 months. Results were graded according to a
      modified Neer classification. RESULTS: The results were excellent in 1 shoulder,
      satisfactory in 4, and unsatisfactory in only 1. One patient continued to have
      severe pain post-operatively, but good pain relief was achieved in the remaining
      shoulders. Average postoperative elevation was 122 degrees, ranging from 90
      degrees to 150 degrees. Complications included pressure ulceration, pneumonia,
      brachial plexopathy, and humeral fracture. CONCLUSIONS: Satisfactory outcomes in
      pain relief and range of motion can be accomplished with shoulder arthroplasty in
      the paraplegic patient. Complications are frequent and careful management of the
      patient necessary to minimize their occurrence.

PMID- 19766020
TI  - Long-term results with Bankart procedure: a 26-year follow-up study of 50 cases.
AB  - BACKGROUND: The purpose of this study was to evaluate the long-term outcome (>20
      years) of patients who underwent an open Bankart procedure, many of them contact
      athletes, in terms of shoulder stability, return to sport, and the development of
      osteoarthritis. METHODS: We retrospectively reviewed 49 patients (50 shoulders)
      who underwent an open Bankart procedure for recurrent shoulder instability. There
      were 36 contact athletes (73%) in this cohort. Mean follow-up was 28 years (25
      32). Clinical examination was performed by an independent reviewer, with standard
      shoulder radiographs obtained. RESULTS: Eight patients had recurrence of
      dislocation after a new traumatic episode, in six cases while playing rugby, with
      two of them requiring re-operation. Forty (82%) patients returned to their
      previous level of sports activities, including all 31 rugby players. No
      statistically significant loss of motion occurred in this group, although there
      was slight loss of flexion (6 degrees ) and external rotation (9 degrees ). The
      mean Rowe score at final follow-up was 82 (25-97), and all but two patients
      considered themselves satisfied with the results of the surgery. Thirty-four
      (69%) patients showed signs of osteoarthritis at follow-up, as follows: Stage 1 
      18, Stage 2 - 5, Stage 3 - 5, and Stage 4 - 1. CONCLUSION: At long-term follow
      up, patients undergoing an open Bankart procedure for recurrent shoulder
      instability obtained a high percentage of shoulder stability, and reliably
      returned to high-level sports activities. However, 69% did show radiographic
      signs of osteoarthritis.

PMID- 19766021
TI  - Impact of work-related compensation claims on surgical outcome of patients with
      rotator cuff related pathologies: a matched case-control study.
AB  - BACKGROUND: The purpose of this matched case-control study was to examine the
      impact of an active compensation claim following a work-related shoulder injury
      on reporting disability, as measured by subjective and objective outcomes at 1
      year postoperatively. METHODS: Data of 517 consecutive patients who had undergone
      a decompression or rotator cuff repair were reviewed. One-hundred and ten
      patients were on compensation related to their shoulder problems. These patients
      were matched with a historical control group (patients without a compensation
      claim) based on age, sex, and level of pathology. Outcome measures used were the
      Western Ontario Rotator Cuff Index, the American Shoulder and Elbow Score, and
      the Constant-Murley score. Nonparametric Wilcoxon and Ranked sign tests were
      conducted to examine the difference between and within groups. RESULTS: Data of
      220 patients were used for analysis (mean age, 48+/-10; range, 20-69). Out of 110
      patients in each group, 45 patients (41%) had undergone a repair and 65 (59%) had
      undergone a decompression surgery (acromioplasty with or without resection of
      lateral clavicle). Both groups improved significantly regardless of their claim
      status (P < .0001). There was a significant difference between injured and
      noninjured workers at baseline, 1-year postoperatively, and in overall
      improvement with the compensation group having a significantly higher level of
      disability. CONCLUSION: Our results show that although injured workers report a
      statistically significant higher level of disability before and after rotator
      cuff surgery, they still show significant improvement 1 year following
      decompression or repair of the rotator cuff tendon(s).

PMID- 19766022
TI  - Anchor fracture leading to supraspinatus failure.

PMID- 19766023
TI  - Prevalence of human papillomavirus (HPV) DNA in oral mucosa of men with
      anogenital HPV infection.
AB  - OBJECTIVE: The aim of the present study was to determine the prevalence of
      concurrent oral and anogenital human papillomavirus (HPV) infection in male
      patients using polymerase chain reaction and reverse hybridization. STUDY DESIGN:
      Thirty consecutive men were recruited among those attending the Clinic for
      Sexually Transmitted Diseases of the Outpatient Department of Dermatology and
      Sexually Transmitted Diseases, Santa Casa Hospital, Sao Paulo. The criteria for
      enrollment in the study were: age between 15 and 60 years, negative human
      immunodeficiency virus (HIV) status, and the presence of HPV anogenital lesion(s)
      confirmed by polymerase chain reaction and reverse hybridization. As a part of
      their management, all patients were subjected to punch biopsy of the anogenital
      lesions to confirm HPV and an HIV blood test to ensure that they were HIV
      negative. All patients had their oral mucosa examined with an artificial light.
      All oral lesions were sampled by biopsy, and subjects with no detectable lesions
      were sampled by oral mucosal scraping for HPV testing by polymerase chain
      reaction and reverse hybridization. All patients also completed a questionnaire
      that recorded their sexual preferences (heterosexual or homosexual, monogamous or
      polygamous), frequency of sexual activity, practice of oral and/or anal sex, and
      the use of condoms. RESULTS: Only 3 patients presented with a clinically
      detectable oral lesion. Among them, just 1 was HPV positive by the molecular
      assay. In all of the other patients (27 out of 30), oral clinical lesions were
      not detected and scrapings were all negative for HPV infection. CONCLUSION: The
      prevalence of concurrent oral and anogenital HPV infection was very low in this
      study (1 out of 30).

PMID- 19766024
TI  - Implant placement for periosteal expansion osteogenesis using beta-tricalcium
      phosphate block: an experimental study in dogs.
AB  - OBJECTIVES: This study was performed to evaluate the clinical outcome of
      periosteal expansion osteogenesis for correction of a horizontally deficient
      alveolar ridge, stability of dental implants placed in the expanded areas, and
      osteocompatibility of beta-tricalcium phosphate (beta-TCP) block areas. STUDY
      DESIGN: The mandibular premolars were extracted and buccal corticotomy was
      performed in 5 female dogs. Narrow alveolar ridge models were produced at 10
      weeks. The beta-TCP block was placed at the lateral surface of the mandibular
      bone and 2 titanium screws were inserted from the lingual aspect to push the
      block to the buccal side. After a latency period of 8 days, during which time
      primary wound healing occurred, the lingual screws were advanced by approximately
      0.5 mm/day for 6 days. The expansion areas were left untreated for 8 weeks. Then
      implants (diameter 3.5 mm, length 9 mm) were inserted into the gap between the
      beta-TCP block and the original alveolar bone. We evaluated the changes in
      alveolar width, resonance frequency analysis of implants, and histomorphometric
      analysis of the beta-TCP block. RESULTS: No problems with the materials were
      observed at any of the sites of intervention before, during, or at the end of the
      experimental period. The width increased after expansion and showed stable
      results on week 8 from the end of expansion. Implants were placed in the
      expansion area and showed sufficient stability with slight increases in the
      implant stability quotient value until 8 weeks after implant placement. The
      amount of remaining beta-TCP decreased significantly compared with the original
      amount of material inserted. The mean values remaining inside the block were 44.6
      +/- 8.2% and 32.1 +/- 12.0% at 8 and 16 weeks of consolidation, respectively,
      whereas newly formed bone comprised 20.2 +/- 7.2% and 33.5 +/- 9.5%,
      respectively. CONCLUSIONS: Newly formed bone could be acquired by periosteal
      expansion osteogenesis using a beta-TCP block for implant placement in a dog
      model. However, the bone volume was not stable after implant placement despite
      sufficient implant stability for 8 weeks.

PMID- 19766025
TI  - The Emperor's new cloth.

PMID- 19766026
TI  - Equine gammaherpesviruses: pathogenesis, epidemiology and diagnosis.
AB  - Equine gammaherpesviruses (gammaEHV) have been widely studied over the past 45
      years and many isolates have been characterised. Despite this, the diagnosis of
      gammaEHV infection remains difficult to establish as its clinical manifestations
      lack specificity, ranging from mild respiratory signs in a small number of
      animals to outbreaks in large groups of young horses. This review focuses on the
      epidemiology, pathogenesis, clinical manifestations and diagnosis of equine
      herpesvirus (EHV)-2 and -5 infections, as well as on the genetic variation of
      these viruses. Study of these variations has resulted in hypotheses relating to
      viral re-infection and re-activation. Interestingly, the viruses were found to
      contain genetic sequences identical to those of eukaryotic cells which are
      considered central to the development of viral latency through interfering with
      host immune and inflammatory responses. Future molecular biological studies will
      further elucidate the virulence mechanisms of these equine pathogens.

PMID- 19766027
TI  - Use of quantitative real-time PCR for the detection of Salmonella spp. in fecal
      samples from horses at a veterinary teaching hospital.
AB  - A quantitative real-time (RT)-PCR assay was developed to detect Salmonella spp.
      in the feces of 911 equine species admitted to a veterinary hospital. Fresh feces
      and feces enriched for 24h in selenite broth were assessed by conventional
      culture and by RT-PCR targeting the Salmonella invA gene. The detection limit for
      the RT-PCR assay was 3 and 10 organisms, respectively, when spiked samples were
      purified from selenite broth and feces. The analytical specificity was 100% based
      on the detection of a panel of 40 salmonella serotypes from five serogroups and
      the lack of cross-reactivity with non-related micro-organisms. Although
      Salmonella spp. were not cultured from fresh feces, the organism was cultured
      from 6/911 (0.6%) of broth-enriched samples. The bacterial load in enriched
      samples varied from 3 to 861,037 salmonella invA gene copies/MUL DNA. The RT-PCR
      assay had an overall relative accuracy of 98%, a relative sensitivity of 100% and
      a relative specificity of 98%, when compared to conventional culture. The
      judicious use of such a RT-PCR method has the potential to reduce the risk of
      nosocomial infections such as salmonellosis through the provision of highly
      accurate and rapid pathogen detection.

PMID- 19766028
TI  - Numerical rating scale for self-report of pain intensity in children and
      adolescents: recent progress and further questions.

PMID- 19766029
TI  - Genome wide analysis and comparative docking studies of new diaryl furan
      derivatives against human cyclooxygenase-2, lipoxygenase, thromboxane synthase
      and prostacyclin synthase enzymes involved in inflammatory pathway.
AB  - In an effort to develop potent anti-inflammatory and antithrombotic drugs, a
      series of new 4-(2-phenyltetrahydrofuran-3-yl) benzene sulfonamide analogs were
      designed and docked against homology models of human cyclooxygenase-2 (COX-2),
      lipoxygenase and thromboxane synthase enzymes built using MODELLER 7v7 software
      and refined by molecular dynamics for 2 ns in a solvated layer. Validation of
      these homology models by procheck, verify-3D and ERRAT programs revealed that
      these models are highly reliable. Docking studies of 4-(2-phenyltetrahydrofuran-3
      yl) benzene sulfonamide analogs designed by substituting different chemical
      groups on benzene rings replacing 1H pyrazole in celecoxib with five membered
      thiophene, furan, 1H pyrrole, 1H imidazole, thiazole and 1,3-oxazole showed that
      diaryl furan molecules showed good binding affinity towards mouse COX-2. Further,
      docking studies of diaryl furan derivatives are likely to have superior
      thromboxane synthase and COX-2 selectivity. Docking studies against site directed
      mutagenesis of Arg120Ala, Ser530Ala, Ser530Met and Tyr355Phe enzymes displayed
      the effect of inhibition of COX-2. Drug likeliness and activity decay for these
      inhibitors showed that these molecules act as best drugs at very low
      concentrations.

PMID- 19766030
TI  - Prediction of body composition from spine and hip bone densitometry.
AB  - Body mass index (BMI) is used to assess overweight and obesity, but it does not
      account for the distribution or composition of excess weight. Dual-energy X-ray
      absorptiometry (DXA) is widely used for the assessment of osteoporosis. We
      hypothesized that measures of regional fat tissue composition from spine and hip
      DXA done for osteoporosis assessment could be used to estimate body composition
      more accurately than with BMI. We identified 427 adult patients who underwent DXA
      evaluation of the lumbar spine, hip, and whole body at the same visit. The
      population was randomly divided into 2 equal-sized subgroups: one used to derive
      prediction equations for whole-body fat tissue, whole-body lean tissue, and trunk
      fat tissue, and the other for independent validation. The estimates were compared
      with the actual measurements from the whole-body scans. In all analyses,
      prediction using the regional DXA scans outperformed prediction using BMI or its
      component variables, height and weight. When the predicted and actual
      measurements were compared in the validation cohort, regression slopes did not
      differ significantly from unity and the intercepts did not differ significantly
      from zero. We conclude that regional DXA scans of the spine and hip can be used
      to accurately measure body composition. Further research is needed to see whether
      these measures can in turn predict the metabolic complications associated with
      overweight and obesity.

PMID- 19766031
TI  - Modeling pathways for low bone mass in children with malignancies.
AB  - Children with malignancies have low bone mass. Pathways for metabolic bone
      disease were investigated in children with cancer by concomitantly assessing
      lifestyle, clinical, and biochemical predictors of bone mass. Forty-one children
      who were receiving cancer therapy for 61 weeks and 39 controls were studied. Data
      on lifestyle factors, biochemical and hormonal parameters, dual-energy X-ray
      absorptiometry bone mass measurements, body composition, and bone age were
      obtained. Compared with controls, patients had higher weight percentile and fat
      mass, a 6-month delay in bone age, and lower estradiol levels. They also had
      higher parathyroid hormone levels and lower bone remodeling markers and bone
      mass. Age, height, lean mass, fat mass, and bone maturation correlated positively
      with several bone mass variables, so did serum estradiol, testosterone, and
      markers of bone remodeling. Conversely, corticosteroids, methotrexate (MTX), and
      intrathecal therapy negatively correlated with bone mass at the spine and hip (R
      = -0.33 to 0.40, p < 0.04). In the adjusted analyses, bone maturation, serum
      osteocalcin level, MTX, and intrathecal therapy were significant predictors of
      lumbar spine and total body Z-scores, bone maturation accounting for the largest
      proportion in Z-score variance. Chemotherapy-induced delay in bone maturation and
      suppression of bone modeling are major pathophysiologic pathways predicting bone
      mass in children with malignancies.

PMID- 19766032
TI  - Evaluation of a simple management protocol for hyperglycaemic crises using
      intramuscular insulin in a resource-limited setting.
AB  - BACKGROUND: Management of hyperglycaemic crises requires expensive and labour
      intensive procedures that are not achievable in all clinical settings.
      Intramuscular (IM) insulin therapy is a more feasible alternative, but remains
      insufficiently evaluated. We report here on an audit of clinical outcomes of a
      simple management protocol that involves IM insulin therapy, careful rehydration
      and inexpensive monitoring in a resource-limited setting. METHODS: In June 2006,
      we began the routine use of a protocol based on IM insulin administration,
      careful rehydration and affordable monitoring for the management of
      hyperglycaemic crises in Yaounde Central Hospital. Clinical records of patients
      admitted for hyperglycaemic crises 6 months before and 6 months after
      introduction of the protocol were independently coded and compared for clinical
      outcomes, including the 48-hour death rate as a primary endpoint. Secondary
      endpoints were blood glucose (BG) normalization and duration of hospital stay.
      RESULTS: A total of 112 patients' files fulfilled the inclusion criteria,
      including 57 before and 55 after the introduction of the IM protocol
      (intervention). Patients of the pre-intervention group were aged 56.4+/-2.1 years
      versus 53.9+/-2.3 years in the intervention group (p=0.41), with 23% versus 40%,
      respectively, with newly diagnosed diabetes (p=0.05), and 45% versus 41%,
      respectively, with significant ketosis on admission (p=0.84). As for the primary
      endpoint, 15.8% of the pre-intervention group died within 48 hours of admission
      versus 3.6% in the intervention group (p=0.03). BG was normalized within 24 hours
      of admission in 28.1% patients of the pre-intervention group versus 90.9% of the
      intervention group (p<0.001). However, the overall duration of hospitalization
      was similar in both groups. Septic shock, ketosis and high serum creatinine on
      admission were associated with poor outcomes in both groups. CONCLUSION: The
      proposed protocol using IM insulin can be safely used to treat hyperglycaemic
      crises, with mortality rates comparable to those in specialized centres in
      developed countries.

PMID- 19766033
TI  - [Volar transscaphoid perilunate fracture dislocation. A case report].
AB  - Volar perilunar dislocations of the carpus are rare. They occur in young patients
      following a violent injury. Open reduction is often needed because of instability
      of the lesion. The authors report a case of volar transscaphoid perilunate
      fracture-dislocation treated surgically, with a satisfactory functional result
      after a follow-up of two and a half years.

PMID- 19766034
TI  - [Analysis of acute distal radius fractures with the articular sagittal index
      (ASI)].
AB  - Displacements of articular fragments are not always visible on initial
      radiographs of acute distal radius fractures. Despite the wide use of CT scan, it
      may be useful to know a simple index that could suggest an articular displaced
      fracture from the initial standard radiographs. The authors describe an articular
      sagittal index (ASI) of the distal radius and provide reference values from a
      study of 100 healthy volunteers. An increase of the ASI index suggests a
      displaced articular distal radius fracture with possible impaction.

PMID- 19766035
TI  - Desmoid tumor of the forearm. Reconstructive surgery and functional result.
AB  - Functional results after resection-reconstruction operated at the same time.
      Desmoid tumors, also known as aggressive fibromatosis, are benign locally
      aggressive tumors with a high rate of recurrence. Most authors recommend surgical
      treatment with wide-free margin. Achieving margins of normal tissue around an
      upper extremity lesion without creating significant functional compromise is
      frequently difficult. Therefore, functional reconstructive surgery is important,
      considering that for most patients treated for these tumors, the life expectancy
      is high and considering also that wide resection can affect the function and the
      aesthetics as well. We present a case of aggressive fibromatosis in the proximal
      third of the forearm treated by wide resection and reconstructive surgery in one
      single procedure, with an acceptable functional result with no evidence of
      recurrence at 3 years of follow-up.

PMID- 19766036
TI  - The future of robotics in hand surgery.
AB  - Robotics has spread over many surgical fields over the last decade: orthopaedic,
      cardiovascular, urologic, gynaecologic surgery and various other types of
      surgery. There are five different types of robots: passive, semiactive and active
      robots, telemanipulators and simulators. Hand surgery is at a crossroad between
      orthopaedic surgery, plastic surgery and microsurgery; it has to deal with fixing
      all sorts of tissues from bone to soft tissues. To our knowledge, there is not
      any paper focusing on potential clinical applications in this realm, even though
      robotics could be helpful for hand surgery. One must point out the numerous works
      on bone tissue with regard to passive robots (such as fluoroscopic navigation as
      an ancillary for percutaneous screwing in the scaphoid bone). Telemanipulators,
      especially in microsurgery, can improve surgical motion by suppressing
      physiological tremor thanks to movement demultiplication (experimental vascular
      and nervous sutures previously published). To date, the robotic technology has
      not yet become simple-to-use, cheap and flawless but in the future, it will
      probably be of great technical help, and even allow remote-controlled surgery
      overseas.

PMID- 19766037
TI  - [Unexpected in vitro fertilization failure in patients with normal sperm: a
      proteomic analysis].
AB  - OBJECTIVE: Despite normal sperm parameters, 5% of in vitro fertilization (IVF)
      attempts result in an unpredictable failure of fertilization. In 56% of the
      cases, there is no obvious oocyte anomaly, but lack of sperm binding to the zona
      pellucida. This study aims to contribute to clarify the male molecular causes of
      failures in IVF, which are undetected by classical sperm analysis. PATIENTS AND
      METHODS: The spermatic proteomic profiles of patients, with a complete failure of
      fertilization and no spermatozoa bound to the zona pellucida, is compared to
      controls (patients with normal fertilization and cleavage rates after a classical
      IVF for tubal indication). All samples are analysed by 2 Dimensional
      Electrophoresis-Differential In Gel Electrophoresis (2DE-DIGE) after being
      divided into three fractions according to their isoelectric point (acid,
      intermediate and basic). RESULTS: Fourteen proteins differentially expressed
      between all the cases and all the controls were highlighted. Twelve of these
      proteins were identified by mass spectrometry (six from the acid fraction and six
      from the basic fraction). Two of these proteins may have an interest in gametic
      interaction: the laminin receptor LR67 and the L-xylulose reductase. DISCUSSION
      AND CONCLUSION: More investigation is needed to understand the involvement of the
      identified proteins in the IVF fertilization failure of the infertile patients in
      this study.

PMID- 19766038
TI  - [Medical abortion at home and at hospital: a trial of efficacy and
      acceptability].
AB  - OBJECTIVES: To evaluate the efficacy and the acceptability of medical abortion at
      home and at hospital. PATIENTS AND METHODS: From 11 February 2008 to 16 July
      2008, 399 patients were included in the study: 173 at home and 226 at hospital.
      RESULTS: Efficacy was evaluated for 305 patients because 94 were lost of follow
      up (23.6%). Efficacy of medical abortion was 86.7% (124/143) at home and 95.8%
      (155/162) at hospital. There were one ongoing pregnancy and 25 surgical
      aspirations (8.6%). The family planning nurse received a phone call from five
      patients after mifepristone at home (2.9%) and seven patients after mifepristone
      at hospital (3.1%). Only one patient "at home" had an emergency consultation
      (0.6%) and nine patients "at hospital" (4%). Ten patients went back to their
      gynecologist before their appointment for follow-up (2.5%): five "at home" (2.9%)
      and five "at hospital" (2.2%). Thirteen patients were referred by the private
      provider to the hospital medical specialist. Acceptability is known for 70.2% of
      patients: 98% thought that medical abortion at home was acceptable and 92.9% at
      hospital. DISCUSSION AND CONCLUSION: The failure rate of medical abortion is
      higher at home and is due to aspirations for incomplete abortion. The procedure
      at home seems to be more acceptable than at hospital. It will be interesting to
      realize a prospective randomized study to compare the procedures at home and at
      hospital.

PMID- 19766039
TI  - [Pregnancy associated Plasmodium falciparum malaria discovered fortuitously:
      report of two cases].
AB  - We report two cases of pregnancy-associated Plasmodium falciparum malaria
      discovered fortuitously. These two women were born in Africa and their last visit
      in an endemic area was more than one year before. It is well known that pregnancy
      is one of major risks of late onset of P. falciparum malaria. In the two cases
      reported in this study, clinical signs of malaria were not specific and we will
      describe the interest to detect more systematically pregnant African women, first
      arrival immigrants.

PMID- 19766040
TI  - [The ten commandments for successful oral communication... at least, what it
      sounds like!].

PMID- 19766041
TI  - [Postoperative long-term amenorrhea avoids recurrence of endometriosis: finally
      the proof!].

PMID- 19766042
TI  - [How to avoid complications with the Cho hemostatic sutures?].

PMID- 19766043
TI  - [Atypical ductal and lobular hyperplasia of the breast].
AB  - Atypical hyperplasia represents 4% of all benign breast diseases. There are two
      different types: atypical ductal hyperplasia and atypical lobular hyperplasia.
      Aside columnar cell lesion. They represent an early stage of some forms of low
      grade carcinoma in situ and invasive carcinomas. Atypical hyperplasia is a benign
      lesion with intermediate carcinologic risk and the existence of a concomitant
      aggressive lesion should be suspected. When atypical lesion is found on a biopsy
      specimen, surgical excision is recommended especially in case of atypical ductal
      hyperplasia. A regular supervision is recommended.

PMID- 19766044
TI  - [Vitrification: a future technique for ovarian cryopreservation? Physical basis
      of cryobiology, advantages and limits].
AB  - Ovarian cryopreservation is presently indicated in patients who undergo a
      gonadotoxic treatment, most commonly for anticancer procedures. These procedures
      can strongly alter fertility by damaging the follicular ovarian reserve. Although
      six human live births have been described in the world after ovarian tissue
      cryopreservation and autografting, the techniques of cryopreservation techniques
      are not consensual. Vitrification is a physical process that allows
      cryopreservation without formation of ice crystals, by transformation of a highly
      concentrated solution in a glassy or amorphous state. Vitrification is at present
      rapidly expanding in the biology of reproduction. With the classic methods of
      freezing, formation of ice crystals within the ovarian tissue is systematic and
      can entail cellular lesions. Which is why more and more teams question the
      theoretical advantage of the vitrification for ovarian cryopreservation. Our
      objective was to summarize the fundamental physical basis of cryobiology,
      necessary for an understanding of vitrification. From our experience, we also
      wanted to point out the practical difficulties of this technique, and we are
      proposing a model of evaluation and validation that uses differential scanning
      calorimetry, applicable to any protocol of vitrification.

PMID- 19766045
TI  - [No chief clinical officer post at the public hospital! Shame on you, or
      what...?].

PMID- 19766047
TI  - [Debate for: hysterectomy in locally advanced cervical cancer].

PMID- 19766048
TI  - [Role of sentinel node biopsy in early-stage cervical cancer in the therapeutic
      strategy].
AB  - Early-stage cervical cancer (IA2 and IB1) treatment consists in surgery with a
      radical colpohysterectomy associated to a systematic pelvic lymphadenectomy more
      or less a paraaortic lymphadenectomy (Wertheim-Meigs surgery). Pelvic lymph node
      involvement is the main independent prognostic factor and justifies an adjuvant
      therapy. Sentinel lymph node (SLN) procedure allows a reliable evaluation of the
      lymph node status thanks to an accurate histologic analysis. This procedure is
      still not validated in practice, which means the bilateral pelvic lymphadenectomy
      is systematically done whatever the lymph node status is. Nevertheless the
      purpose of the SLN biopsy in cervical cancer does not consist in avoiding an
      unnecessary lymphadenectomy, which is not really associated with a major
      morbidity. Actually, a better initial stadification would allow to fit to the
      risk of recurrence not only the radicality of the surgery, but also the adjuvant
      therapy. The morbidity of a radical surgery could be limited for good prognosis
      patients and avoided for the benefit of a concomitant chemoradiotherapy.

PMID- 19766049
TI  - [Immediate fetal-maternal morbidity of first instrumental vaginal delivery using
      Thierry's spatulas. A prospective continuous study of 195 fetal extractions].
AB  - OBJECTIVES: To investigate the immediate fetal-maternal morbidity related to
      Thierry's spatula for first instrumental vaginal delivery. PATIENTS AND METHODS:
      We conducted a prospective observational study in Toulouse university hospital,
      including primiparas who vaginally delivered a live singleton cephalic infant>36
      WG, between December 2005 and June 2006. Instrumental deliveries were performed
      using short spatulas in all cases. Outcome measures were: perineal complications
      (episiotomy, laceration and associated lesions, urinary retention, pain at H48),
      neonatal morbidity (cutaneous injuries, neonatal transfer, cord pH, Apgar score).
      Instrumental deliveries were compared with spontaneous vaginal deliveries (SVD).
      RESULTS: Six hundred and eight primiparas were included, distributed in 195
      extractions (32%) and 413 SVD (68%). Spatulas allowed fetal extraction in all
      cases. Main differences between the two groups were: length of labour, occiput
      posterior position (12.8% for spatulas vs 1.7% for SVD; p<0.0001), episiotomy
      rate (97.9% vs 51.3%; p<0.0001), severe perineal lacerations (3.6% vs 0.2%;
      p=0.0007), post-partum morbidity (pain, hematoma, and urinary retention). No case
      of early severe neonatal complication was related to the use of the spatulas.
      DISCUSSION AND CONCLUSIONS: Perineal complications (severe lacerations)
      associated with spatulas are increased with regard to SVD, but comparable to that
      reported with forceps. The main disadvantage is the high frequency of episiotomy,
      which should not be systematic. Neonatal morbidity is reduced. Comparative
      studies (spatulas vs. other procedures) are needed to confirm these data, but
      spatulas remain a multipurpose instrument which should continue to be taught.

PMID- 19766050
TI  - [Hysteroscopic sterilization among women older than forty years: what motivated
      the women?].
AB  - OBJECTIVES: The aim of the study was to check the motivations of the patients
      over 40 years old who want to be sterilized by the Essure system (hysteroscopic
      sterilization). The simplicity of the technique raises the question of the choice
      between contraception and sterilization among women over 40. PATIENTS AND
      METHODS: It is a prospective study concerning 168 women. We report their past
      history and their motivations. We have checked also the satisfaction and
      tolerance of the procedure. RESULTS: The medium number of children by woman was
      2.6. The middle age of the last child was 11.5. Twenty-eight percent of the
      patients underwent at least one abortion. They tried 2.3 methods of contraception
      before accept sterilization. The reasons of their choice were, for 45.9% of them
      the side effects of the contraceptions; in 22% of cases, they were fed up of
      their contraception; in 12% of cases, it was a contraindication to the
      contraceptions, in 10% of cases, a failure of the contraception and in 2% of
      cases, they had have a contraindication to the pregnancy. Ninety-three percent of
      them were satisfied. It is a fast procedure with bearable pain. DISCUSSION AND
      CONCLUSION: Essure system is a good alternative to the contraception in patients
      who present, from 40 years old, some increased risks. It is an easy technique
      with high satisfaction rate.

PMID- 19766051
TI  - A novel method for the diagnosis of drowning by detection of Aeromonas sobria
      with PCR method.
AB  - The acid digestion method has been widely used for the diagnosis of death by
      drowning, but it is not always sensitive. However, there has been no definitive
      method to replace acid digestion until now. We speculate that bacteria are more
      useful markers than plankton for the diagnosis of death by drowning. In this
      study, from the preserved blood samples of 32 freshwater drowning cases, specific
      DNA fragments of Aeromonas sobria, one of the most common aquatic bacteria, were
      examined using PCR. The DNA fragments of the bacterium were detected from 27 of
      32 cases with first round PCR or nested-PCR. The remaining 5 cases in which
      bacterial DNA was not detected had longer storage periods for the blood samples
      and shorter time intervals from drowning to death. These results indicate that
      the present method can be applied to the diagnosis of death by drowning.

PMID- 19766052
TI  - Recent development in carbohydrate-based cancer vaccines.
AB  - Tumor-associated carbohydrate antigens (TACAs) are important molecular markers on
      the cancer cell surface, useful for the development of therapeutic cancer
      vaccines or cancer immunotherapies. However, because of their poor immunogenicity
      and/or immunotolerance, most TACAs fail to induce T cell-mediated immunity that
      is critical for cancer therapy. This review summarizes the recent effort to
      overcome this problem via constructing TACA conjugates with improved
      immunogenicity, such as by covalently coupling TACAs to proper carrier molecules
      to form clustered or multi-epitopic conjugate vaccines, coupling TACAs to a T
      cell peptide epitope and/or an immunostimulant epitope to form fully synthetic
      multi-component glycoconjugate vaccines, and developing vaccines based on
      chemically modified TACAs, which is combined with metabolic engineering of cancer
      cells.

PMID- 19766053
TI  - Electrochemical, catalytic and antimicrobial activities of N-functionalized
      cyclam based unsymmetrical dicompartmental binuclear nickel(II) complexes.
AB  - Five binuclear nickel(II) complexes have been prepared by simple Schiff base
      condensation of the compound 1,8-[bis(3-formyl-2-hydroxy-5-bromo)benzyl]-l,4,8,11
      tetraazacyclotetradecane (L) with appropriate aliphatic or aromatic diamine,
      nickel(II) perchlorate and triethylamine. All the complexes were characterized by
      elemental and spectral analysis. Positive ion FAB mass spectra show the presence
      of dinickel core in the complexes. The electronic spectra of the complexes show
      red shift in the d-d transition. Electrochemical studies of the complexes show
      two irreversible one electron reduction processes in the range of 0 to -1.4V. The
      reduction potential of the complexes shifts towards anodically upon increasing
      chain length of the macrocyclic ring. All the nickel(II) complexes show two
      irreversible one electron oxidation waves in the range 0.4-1.6V. The observed
      rate constant values for catalysis of the hydrolysis of 4-nitrophenyl phosphate
      are in the range of 1.36x10(-2)-9.14x10(-2)min(-1). The rate constant values for
      the complexes containing aliphatic diimines are found to be higher than the
      complexes containing aromatic diimines. Spectral, electrochemical and catalytic
      studies of the complexes were compared on the basis of increasing chain length of
      the imine compartment. All the complexes show higher antimicrobial activity than
      the ligand and metal salt.

PMID- 19766054
TI  - Analysis of communicative behaviour: profiling roles and activities.
AB  - OBJECTIVES: In this paper we present a method for processing and presentation of
      data recorded through structured observation of clinicians' information and
      communication activities. The activities are encoded as sequences of distinctive
      speech acts, and resulting profiles of communicative behaviour are visualized in
      radar graphs. Example profiles resulting from the analysis of three clinicians'
      communicative behaviour during pre-rounds meetings and medication activities are
      given. METHODS: The communicative acts profiles are based on empirical data from
      an observational study performed at a Norwegian university hospital. A fifth-year
      medical student spent 20 days in two different hospital wards, following one
      physician at a time in daily, patient-centred work. The observer recorded the
      clinicians' information and communication activities during several ward
      situations such as pre-rounds meetings, ward rounds, and patient discharge. The
      data was recorded by means of an observation form consisting of a mixture of
      codes and free-text fields. The recorded data was post-processed by associating
      each event with one predefined communicative act, and resulting profiles for
      three individual physicians in different situations have been created as radar
      graphs. RESULTS/CONCLUSION: The approach is an efficient and useful means for
      studying clinicians' information and communication patterns in hospital wards.
      The method can be used to illustrate variations among individual clinicians in
      similar situations and to compare profiles of different roles or hospital wards.
      Given proper validation, the approach may serve as an important tool to inform
      the design of new clinical information systems.

PMID- 19766055
TI  - Performance and clinical utility of a novel fully automated quantitative HCV-core
      antigen assay.
AB  - BACKGROUND: Recently, a novel quantitative HCVcoreAg immunoassay developed for
      commercialisation by Abbott has become available in Europe and Asia. OBJECTIVES:
      We evaluated the correlation of HCV-RNA and HCVcoreAg and investigated the
      stability of HCVcoreAg and HCV-RNA. STUDY DESIGN: HCVcoreAg was quantified by a
      novel fully automated immunoassay (Architect HCVAg, Abbott, Germany). HCV-RNA
      quantification was performed either using the Cobas-TaqMan assay or Amplicor-HCV
      Monitor (Roche-Diagnostics, Germany). Correlation of HCVcoreAg with HCV-RNA was
      studied cross-sectionally and longitudinally in untreated patients followed for
      up to 8 years. Stability of HCVcoreAg and HCV-RNA was evaluated in plasma and
      whole blood stored for up to 96 h at different conditions. RESULTS: HCVcoreAg
      showed good correlation with HCV-RNA in all 118 cross-sectional tested samples
      irrespective of the HCV genotype (r=0.75). In the majority but not all of the 10
      longitudinally studied patients HCVcoreAg also demonstrated a good correlation
      with HCV-RNA. HCVcoreAg was stable in plasma at 4, 20, and 37 degrees C for up to
      96 h, whereas HCV-RNA significantly declined at 37 degrees C. In whole blood,
      HCVcoreAg and HCV-RNA levels declined at all conditions with exception of
      HCVcoreAg at 37 degrees C. HCVcoreAg was stable after 1-5 freezing/thawing cycles
      and not light-sensitive. CONCLUSIONS: HCVcoreAg represents a stable and reliable
      marker of viral replication showing a good correlation with HCV-RNA irrespective
      of the HCV genotype. HCVcoreAg determination can be used to confirm viral
      replication and monitor viral load or acquisition of HCV over time.

PMID- 19766056
TI  - Neurophysiologic assessment of brain maturation after an 8-week trial of skin-to
      skin contact on preterm infants.
AB  - OBJECTIVE: Skin-to-skin contact (SSC) promotes physiological stability and
      interaction between parents and infants. Analyses of EEG-sleep studies can
      compare functional brain maturation between SSC and non-SSC cohorts. METHODS:
      Sixteen EEG-sleep studies were performed on eight preterm infants who received 8
      weeks of SSC, and compared with two non-SSC cohorts at term (N=126), a preterm
      group corrected to term age and a full-term group. Seven linear and two
      complexity measures were compared (Mann-Whitney U test comparisons p<.05).
      RESULTS: Fewer REMs, more quiet sleep, increased respiratory regularity, longer
      cycles, and less spectral beta were noted for SSC preterm infants compared with
      both control cohorts. Fewer REMs, greater arousals and more quiet sleep were
      noted for SSC infants compared with the non-SSC preterms at term. Three right
      hemispheric regions had greater complexity in the SSC group. Discriminant
      analysis showed that the SSC cohort was closer to the non-SSC full-term cohort.
      CONCLUSIONS: Skin-to-skin contact accelerates brain maturation in healthy preterm
      infants compared with two groups without SSC. SIGNIFICANCE: Combined use of
      linear and complexity analysis strategies offer complementary information
      regarding altered neuronal functions after developmental care interventions. Such
      analyses may be helpful to assess other neuroprotection strategies.

PMID- 19766057
TI  - Two patients with narcolepsy treated by hypnotic psychotherapy.

PMID- 19766058
TI  - Reactive species and diabetes: counteracting oxidative stress to improve health.
AB  - Oxidative stress is at the very core of metabolism. Reactive species behave as
      true second messengers that control important cellular functions. However, under
      pathological conditions, abnormally large concentrations of these species may
      lead to permanent changes in signal transduction and gene expression. Attenuation
      of oxidative stress as a way to improve several diseases such as diabetes has
      flourished as one of the main challenges of research. The lack of evidence to
      prove the benefits from antioxidant compounds has led to boost these strategies.
      Inhibition of reactive oxygen species (ROS) production through the development of
      inhibitors against NADPH oxidase and mitochondria offers an alternative approach
      to conventional antioxidant therapies. There is a need to understand oxidative
      stress process to implement health-disorder approaches.

PMID- 19766059
TI  - The CD4+CD25 bright regulatory T cells and CTLA-4 expression in peripheral and
      decidual lymphocytes are down-regulated in human miscarriage.
AB  - The present study was undertaken to analyze the changes in the proportion of
      CD4(+)CD25(bright) regulatory T (Treg) cells and the expression of costimulatory
      molecules, CTLA-4 and CD28, in the peripheral blood and deciduas in the setting
      of non-pregnancy, normal early pregnancy and miscarriage. In this study, we
      showed that CD4(+)CD25(bright) T cells significantly increased in the peripheral
      of normal pregnancy compared to that of non-pregnancy. The proportions of
      CD4(+)CD25(bright) T cells in both peripheral blood and deciduas were
      significantly lower in miscarriage than that of normal pregnancy.
      CD4(+)CD25(bright) T cells were characterized by high-level FoxP3 expression and
      low-level CD69 expression. An increase in the CD28 mRNA expression was
      accompanied by a decrease in the CTLA-4 mRNA expression in decidual tissues from
      human miscarriage. The ratios of CTLA-4(+)/CD28(+) in miscarriage were
      significantly lower than that of the normal pregnancy both in the peripheral and
      in deciduas. The ratio of CTLA-4(+)/CD28(+) in CD4(+)CD25(bright) T cells was
      significantly higher than that of the CD4(+)CD25(dim) T cells both in normal
      pregnancy and in miscarriage. The decidual T cells in the miscarriage appeared
      higher in responsiveness and IL-2 and IFN-gamma production in comparison with the
      decidual T cells in the early pregnancy. These results above suggest that
      CD4(+)CD25(bright) Treg cells might play a role in the maintenance of pregnancy
      via up-regulation of CTLA-4 expression. The down-regulation of Treg cells and
      their functions, and the imbalance of positive and negative regulators of
      costimulatory signals might lead to an abnormal immune milieu, which confer
      susceptibility to pregnancy loss.

PMID- 19766060
TI  - To sushi or not to sushi: can people with epilepsy have sushi from time to time?

PMID- 19766061
TI  - Digital versus plain film imaging in the operating room: cost and safety
      considerations.

PMID- 19766062
TI  - Laminaria tent vs misoprostol for cervical priming before hysteroscopy:
      Randomized study.
AB  - STUDY OBJECTIVE: To compare the efficacy of laminaria tents and orally
      administered misoprostol in priming the cervix before operative hysteroscopy.
      DESIGN: Randomized, controlled study (Canadian Task Force classification I).
      SETTING: Tertiary medical center. PATIENTS: One hundred twenty premenopausal
      women who underwent operative hysteroscopy between March 2005 and January 2007.
      INTERVENTION: The women were randomized to receive a laminaria tent or
      misoprostol for cervical priming. MEASUREMENTS AND MAIN RESULTS: The primary
      outcomes were postpriming cervical width insofar as size of Hegar dilators and
      need for cervical dilation. The secondary outcomes were adverse effects from the
      priming methods. Postpriming cervical width was greater in the laminaria group
      but not significantly different from that in the misoprostol group. However,
      cervical dilation before hysteroscopy was required in more patients in the
      misoprostol group. Nausea, vomiting, diarrhea, and bleeding were more common in
      the misoprostol group, and the incidences of chills and headache were similar
      between the 2 groups. CONCLUSION: Laminaria tents are superior to oral
      misoprostol insofar as less need for cervical dilation and fewer adverse effects.

PMID- 19766063
TI  - Electrochemical behaviour of dimethyl-2-oxoglutarate on glassy carbon electrode.
AB  - The electrochemical behaviour of dimethyl-2-oxoglutarate (MOG), a key
      intermediate in the Krebs cycle and an important nitrogen transporter in the
      metabolic pathways in biological processes, was investigated by cyclic
      voltammetry, square wave voltammetry and differential pulse voltammetry using a
      glassy carbon electrode. The reduction of MOG is an irreversible diffusion
      controlled process that occurs in a cascade mechanism. For electrolytes with pH
      <3.0 and pH >7.0 one peak occurred and for 3.0<pH<8.0 two peaks corresponding to
      consecutive charge transfer reactions were observed. The effects of scan rate,
      concentration and pH of the electrolyte solution were monitored, and both peaks
      were found to shift cathodically with the increase in pH. DPV measurements
      allowed the determination of the number of electrons and protons i.e., one
      electron and one proton, involved in the reduction mechanism of MOG. Based upon
      the results obtained a reduction mechanism was proposed and the observed waves
      were attributed to the hydroxylation of the keto group of MOG to form dimethyl-2
      hydroxyglutarate. Furthermore, two methodologies for the electroanalytical
      determination of MOG were also compared.

PMID- 19766064
TI  - Development and validation of a sensitive gas chromatography-ammonia chemical
      ionization mass spectrometry method for the determination of tabun enantiomers in
      hemolysed blood and plasma of different species.
AB  - The aim of this study was to develop and validate a fast, sensitive and easily
      applicable GC-MS assay for the chiral quantification of the highly toxic
      organophosphorus compound tabun (O-ethyl-N,N-dimethylphosphoramidocyanidate, GA)
      in hemolysed swine blood for further use in toxicokinetic and toxicodynamic
      studies. These requirements were fulfilled best by a GC-MS assay with positive
      chemical ionization with ammonia (GC-PCI-MS). Separation was carried out on a
      beta-cyclodextrin capillary column (Supelco BetaDex 225) after reversed phase
      (C18) solid-phase extraction. The limit of detection was 1 pg/ml for each
      enantiomer (approximately 500 fg on column) and the limit of quantification 5
      pg/ml. The GC-PCI-MS method was applied for the quantification of tabun
      enantiomers in spiked swine blood after hemolysis and in spiked plasma of
      different species including humans.

PMID- 19766065
TI  - Discriminatory protein binding by a library of 96 new affinity resins: a novel
      dye-affinity chromatography tool-kit.
AB  - Initial acceptance of Cibacron Blue 3G-A based matrices has made dye-ligand
      affinity chromatography an attractive proposition. This prompted the synthesis
      and search for new dye structures. A systematic library of 96 affinity resins was
      generated using novel analogs of Cibacron Blue 3G-A and also by varying spacer
      lengths for immobilization. The library was tested in a batch binding and elution
      mode using seven different proteins--four Aspergillus enzymes namely, NADP
      glutamate dehydrogenase, laccase, glutamine synthetase and arginase, bovine
      pancreatic trypsin and the two serum proteins human serum albumin and
      immunoglobulin G. Unique binding patterns were observed for each of them
      indicating that the library displayed discriminatory interactions. The
      significance of spacer length in the interaction with proteins was discernable.
      Trypsin interacted best with affinity resins that had no spacer. It was possible
      to resolve IgG and HSA from a mixture using a combination of resins. There was a
      good spread of HSA binding capacity in the 96 affinity resins. While some showed
      better HSA binding capacity than the commercial CB3GA-based matrix, a few with
      lower capacity were also observed. Subsequent to an initial screen, one affinity
      resin (CR-017) could be used to enrich Aspergillus terreus NADP-GDH from crude
      cell extracts. The efficacy of this dye-affinity resin was rationalized by
      characterizing NADP-GDH inhibition kinetics with the corresponding free dye
      ligand. In the sum, the library provides a set of dye-ligand affinity matrices
      with a potential for use in high throughput screening for protein purification.

PMID- 19766066
TI  - Determination of six hydroxyalkyl mercapturic acids in human urine using
      hydrophilic interaction liquid chromatography with tandem mass spectrometry
      (HILIC-ESI-MS/MS).
AB  - Mercapturic acids are increasingly used as biomarkers for exposure to certain
      carcinogenic substances. Glycidol, ethylene oxide, propylene oxide, acrolein and
      1,3-butadiene are important intermediates of toxicological concern used in the
      industrial production of various chemicals. The main urinary metabolites of these
      alkylating substances are hydroxyalkyl mercapturic acids. Therefore, we developed
      and validated an analytical method for the simultaneous determination of six
      hydroxyalkyl mercapturic acids in human urine after solid phase extraction. The
      mercapturic acids were separated using hydrophilic interaction liquid
      chromatography (HILIC) and quantified by tandem mass spectrometry using
      isotopically labelled internal standards. The developed method enables for the
      first time the determination of 2,3-dihydroxypropyl mercapturic acid (DHPMA), a
      metabolite of glycidol, in human urine. Additionally, the mercapturic acids of
      ethylene oxide (hydroxyethyl mercapturic acid, HEMA), propylene oxide (2
      hydroxypropyl mercapturic acid, 2-HPMA), acrolein (3-hydroxypropyl mercapturic
      acid, 3-HPMA) as well as of 1,3-butadiene(3,4-dihydroxybutyl mercapturic acid,
      DHBMA and monohydroxy-3-butenyl mercapturic acid, MHBMA) can be determined. The
      limits of detection range from 3.0 to 7.0 MUg/L. Intra- and inter-day precision
      was determined to range from 1% to 9%. Due to the good accuracy and precision and
      the low limits of detection the developed method is well suited for the
      determination of occupational exposure to alkylating substances as well as for
      the determination of background concentrations of the respective mercapturic
      acids in the general population.

PMID- 19766067
TI  - Why no adult stunting penalty or height premium? Estimates from native Amazonians
      in Bolivia.
AB  - Among adults of industrial nations, growth stunting (<-2 SD height Z score) is
      associated with worse indicators of adult well-being (e.g., income). Does adult
      stunting also inflict private costs in traditional societies? Adult stunting
      penalties or height premiums might only emerge when traditional societies
      modernize. Here we estimate the association between adult stunting and indicators
      of adult well-being using data from a panel study in progress among the Tsimane',
      a foraging-farming society of native Amazonians in Bolivia. Subjects included 248
      women and 255 men >or=age 22 measured annually during 5 consecutive years (2002
      2006). Nine outcomes (wealth, monetary income, illness, access to credit, mirth,
      schooling, math skills, plant knowledge, forest clearance) were regressed
      separately against a stunting dummy variable and a wide range of control
      variables. We found no significant association between any of the indicators of
      own well-being and adult stunting. Additional analysis showed that stunting bore
      an association only with poorer mid-arm muscle area. Height premiums and stunting
      penalties, though evident and marked in modern societies, might not be common in
      all traditional societies.

PMID- 19766068
TI  - Transcription factors down-stream of Ras as molecular indicators for targeting
      malignancies with oncolytic herpes virus.
AB  - Overactivation in Ras signaling has been under intensive study as the molecular
      basis for development of cancer. Such overactivation can occur in the presence or
      absence of mutations in Ras gene resulting in activation of a series of down
      stream effectors such as transcription factors. Different studies have shown the
      activation of Ras down-stream effectors in non-Hodgkin lymphoma (NHL) although
      mutations in Ras are not prevalent in this malignancy. Since overactivation in
      Ras signaling also increases permissiveness of cancer cells to infection by
      oncolytic versions of herpes simplex virus (e.g. R3616), we were interested in
      evaluating the value of transcription factors down-stream of Ras as molecular
      indicators for permissiveness to herpes therapy. In order to accomplish this, and
      also to assess the permissiveness of lymphoma cells to infection with R3616, we
      used NHL cell lines Daudi, Jurkat, NC37, Raji, Ramos and ST486. Once the levels
      of phosphorylation (activation) of extracellular-signal regulated kinase (ERK, a
      Ras effector pathway) and its down-stream transcription factor ELK were
      evaluated, Raji and NC37 showed a significant increase in the phosphorylation
      levels of both molecules while ATF2 (another transcription factor down-stream of
      p38-kinase pathway) seemed to be activated in all studied cells. Raji and NC37
      cells were also most permissive cells to infection with R3616 while their
      permissiveness was decreased upon treatment of cells with an inhibitor of ELK-DNA
      binding portraying ERK/ELK as a suitable predictive indicator for selection of
      cancer cells with increased sensitivity to R3616. This study, therefore, for the
      first time documents permissiveness of lymphoma cells to oncolytic herpes viruses
      and introduces ELK as a suitable factor for predicting tumor susceptibility to
      these novel anticancer agents.

PMID- 19766069
TI  - [Recommendations for the care of the healthy normal newborn at delivery and
      during the first postnatal hours].
AB  - Standardised normal newborn care at delivery and during the first hours of life
      is one of the objectives of the Spanish National Society of Neonatology. The
      object of this review is to apply the best evidence possible to the procedures of
      the care of the newborn from delivery and during the first moments after
      delivery; as well as standards and routines in care to improve quality and the
      safety of the newborn. A PubMed (MeSH) review using the key words: term newborn;
      prophylaxis of ophthalmia neonatorum; haemorrhagic disease of the newborn;
      neonatal jaundice; neonatal screening and hospital discharge. Concepts of regular
      care of the healthy newborn at delivery; normal practices in the delivery room;
      prophylaxis of ophthalmia neonatorum; prevention of vitamin K deficiency
      bleeding; care of the umbilical cord; newborn screening and hospital discharge
      are reviewed. The standard of care of the newborn at delivery and during the
      first hours of life have been updated; recommendations based on evidence and on
      experts of the standard committee of the spanish society of neonatology are done.

PMID- 19766070
TI  - [Preservation of fertility in children and adolescents with cancer: current
      situation and future perspectives].
AB  - Advances in antineoplastic therapy have considerably increased survival rates,
      and currently in the setting of paediatric population are higher than 70%. Among
      the potential long-term late effects due to oncological treatment, reproductive
      dysfunction may have a particularly deep impact on the survivors' quality of
      life. Until recently, limited fertility preservation options were available
      before gonadotoxic therapies. In the last few years the development of new
      assisted reproduction techniques, including ovarian cryopreservation, may be
      promising in selected groups of patients. Although, the feasibility of these
      advances in the paediatric and adolescent field have a long way to go, several
      practical and ethical issues deserve a special review before recommending them
      for routine medical practice.

PMID- 19766071
TI  - Ventilatory management and bronchopulmonary dysplasia in preterm infants.
AB  - Improvements in antenatal and neonatal care have resulted in increased survival
      of very preterm infants. However, the incidence of bronchopulmonary dysplasia
      (BPD) has not changed, probably as a consequence of a demographic shift. The
      underlying pathophysiology of BPD appears to differ for the current population of
      preterm infants compared to that described by Northway et al., and management
      strategies should be targeted to limit ventilator-induced lung injury. Non
      invasive respiratory support techniques are currently under evaluation, but
      results of the trials have thus far failed to show a reduction in BPD. This
      review will focus upon various ventilation modalities for preventing and managing
      bronchopulmonary dysplasia.

PMID- 19766072
TI  - Customised fabricated implants after previous failed cranioplasty.
AB  - Reconstruction of cranial defects can be reasonably considered a failure if an
      aesthetically obvious cranial contour deformity persists after surgery. Such
      unsatisfactory outcome often results from variable resorption of bone grafts or
      infection, requiring removal of implant. In considering further treatment for
      such failed cases, the use of alloplastic implants is frequently warned as
      imprudent due to their theoretically increased potential for infection; however,
      the validity of such caution has never been substantiated. We describe a user
      friendly, time- and cost-effective method of producing prefabricated methyl
      methacrylate implants for the reconstruction of cranial defects, using readily
      available computer-aided design and computer-aided manufacture facilities. This
      method was carried out in 31 patients who presented with persistent cranial
      defects after previously failed cranioplasty. The efficacy of this technique and
      the clinical outcome of the patients in this series were analysed. All implants
      produced a precise fit, with a reduction in operating time and satisfactory
      cosmesis having been achieved. Infection that required removal of implant
      occurred in three patients (9.7%), and one patient developed a dural tear,
      requiring repair. Customised fabricated alloplastic implants provide a safe,
      accurate and efficient way of restoring normal cranial contours in patients with
      cranial defects who have had previous failed cranioplasties.

PMID- 19766073
TI  - Critical approach to medical advice is best for mothers: Midwives play key role.

PMID- 19766074
TI  - Derivation of insulin-producing cells from human embryonic stem cells.
AB  - The potential of pluripotent human cells, such as human embryonic stem cells
      (hESCs) and induced pluripotent stem (iPS) cells, to differentiate into any adult
      cell type makes them ideally suited for the generation of various somatic cells
      and tissues in vitro. This remarkable differentiation capacity permits analyzing
      aspects of human embryonic development in the laboratory, as well as generating
      specialized adult human cells for screening drugs, and for replacing tissues
      damaged by injury or degenerative diseases, such as diabetes. Understanding and
      controlling the fundamental processes that drive the differentiation of
      specialized cells are the keys to the eventual application of this technology to
      patients. In this review, we discuss the different protocols developed that are
      aimed at deriving beta-cells from hESCs. Despite many differences, successful
      strategies share a general adherence to the normal differentiation pathway
      through definitive endoderm. Mimicking normal pancreagenesis offers the best
      strategy for producing glucose-responsive insulin-producing cells in vitro for
      people with diabetes.

PMID- 19766075
TI  - Radial head fractures: treatment by prosthetic replacement.

PMID- 19766076
TI  - Age-specific breast, uterine and ovarian cancer mortality trends in Spain:
      changes from 1980 to 2006.
AB  - INTRODUCTION: Cancers of the breast, uterus and ovary are responsible for 30% of
      the cancer deaths in Spanish women. In recent decades, Spain has experienced
      important socioeconomic transformations, which may have affected mortality
      trends. We present the current situation of mortality in Spain due to cancers of
      the breast, uterus and ovary, as well as trends over 1980-2006. METHODS: Data on
      population and deaths due to cancers of the breast, uterus and ovary were
      obtained from records of the National Statistics Institute. Overall and age
      specific changes in mortality of these tumors were studied using change-point
      Poisson regression models. RESULTS: Breast cancer was responsible for more than
      140,000 deaths of females in 1980-2006. Trend analysis of breast cancer mortality
      of women of all ages showed that rates increased 2.9% annually until 1992 (95%
      confidence interval (CI)=2.5, 3.3). After 1992, mortality declined steadily at a
      rate of -2.1% per year (95% CI=-2.4, -1.8). The number of deaths due to cancers
      of the uterus was 49,287 between the years 1980 and 2006. Uterine cancer
      mortality registered a steady decrease of -1.9% every year since 1980 (95% CI=
      2.1, -1.8). Ovarian cancer caused 36,157 deaths during the same period, with
      rates in women older than 50 years more than ten-fold those of younger women.
      Trend analysis showed a sharp increase of mortality up to 1998 (4.4% annually;
      95% CI=3.9, 4.8) followed by a stabilization. CONCLUSION: The downturn observed
      in mortality for these tumors mainly reflects improved survival as a result of
      earlier diagnosis and better cancer treatments. Cancer management is moving in
      the right direction in Spain.

PMID- 19766077
TI  - Association of DLC1 gene polymorphism with susceptibility to hepatocellular
      carcinoma in Chinese hepatitis B virus carriers.
AB  - BACKGROUND: Lost or downexpression of the gene deleted in liver cancer 1 (DLC1)
      has been implicated in the development of hepatocellular carcinoma (HCC). We
      examined the relationship between DLC1 polymorphisms and HCC risk among Chinese.
      METHODS: Three DLC1 polymorphisms, Ex11+255T>G (rs3739298), Ex11-620G>A
      (rs532841) and IVS19+108C>T (rs621554), were genotyped in 434 patients with HCC
      and 480 controls by PCR-RFLP. The associations with the susceptibility to HCC
      were evaluated while controlling for confounding factors. RESULTS: We observed
      significantly increased susceptibility to HCC for the C/C genotype compared with
      T/T of IVS19+108C>T in the HBV carriers (OR=2.95, 95% CI, 1.65-5.26, P<0.001).
      Compared with the haplotype G-A-T (in order of Ex11+255T>G, Ex11-620G>A and
      IVS19+108C>T), the haplotype T-G-C was also significantly associated with an
      increased susceptibility to HCC among HBV carriers (OR=2.16, 95% CI, 1.08-4.35,
      P=0.009). The stratified analysis indicated no modification of the confounding
      factors on the increased susceptibility to HCC related to the DLC1
      polymorphism/haplotype. CONCLUSIONS: Our findings suggest that DLC1 genetic
      polymorphism or haplotype play a role in mediating the susceptibility to HBV
      related HCC.

PMID- 19766078
TI  - Translating inflammatory bowel disease research into clinical medicine.
AB  - Recent studies have provided important insights into the pathogenesis of
      inflammatory bowel disease (IBD). The development of new therapeutic agents has
      been triggered by basic research and studies in mouse models of IBD. It is
      expected that improved translational research will lead to optimized therapy and
      new individualized treatment options.

PMID- 19766079
TI  - Rethinking the pathogenesis of asthma.
AB  - Asthma research has focused primarily on allergic pathways on the basis that the
      majority of asthma is associated with atopy, the recruitment of the Th2-type T
      cell, the cytokines, and the chemokines that are released on exposure to
      allergens, and the IgE pathway. However, despite considerable investment by
      industry, targeting these pathways has not resulted in new treatments being
      developed beyond blockade of cysteinyl leukotrienes and IgE and improvements in
      inhaled corticosteroids and beta(2)-adrenoceptor bronchodilators. Increasingly,
      it is recognized that asthma is a heterogeneous disorder, and while important,
      allergen sensitization is only one component of the disease, with many other
      environmental and genetic factors playing a role. In addition, these factors act
      locally on a susceptible airway epithelium that is both structurally and
      functionally deficient. It may be worthwhile to focus on increasing the
      resilience of the airways to environmental insults in addition to improving
      strategies that modify adaptive immunity or suppress inflammation.

PMID- 19766080
TI  - Immune responses to the microbiota at the intestinal mucosal surface.
AB  - The mammalian intestinal mucosal surface is continuously exposed to a complex and
      dynamic community of microorganisms. These microbes establish symbiotic
      relationships with their hosts, making important contributions to metabolism and
      digestive efficiency. The intestinal epithelial surface is the primary interface
      between the vast microbiota and internal host tissues. Given the enormous numbers
      of enteric bacteria and the persistent threat of opportunistic invasion, it is
      crucial that mammalian hosts monitor and regulate microbial interactions with
      intestinal epithelial surfaces. Here we discuss recent insights into how the
      innate and adaptive arms of the immune system collaborate to maintain homeostasis
      at the luminal surface of the intestinal host-microbial interface. These findings
      are also yielding a better understanding of how symbiotic host-microbial
      relationships can break down in inflammatory bowel disease.

PMID- 19766081
TI  - The multifaceted influence of the mucosal microflora on mucosal dendritic cell
      responses.
AB  - Over the last decade, it has become apparent that the complex interactions
      between components of the mucosal microflora and the mucosal immune system can
      involve either direct contact with dendritic cells in the lamina propria or,
      alternatively, contact with epithelial cells lining the mucosa that then
      influence the function of dendritic cells. Although in some cases these
      interactions involve signaling specific to particular organisms and in others, to
      classes of organisms, a common theme is that signaling is invariably channeled
      through receptors that address many organisms or all organisms such as the
      pattern-recognition receptors TLR and NLR. Here, I review this information with
      the intention of identifying how the mucosal microflora influences specific
      functions of the mucosal immune system such the production of particular
      cytokines as well as broader functions such as the maintenance of mucosal immune
      homeostasis and host defense.

PMID- 19766082
TI  - Intestinal effector T cells in health and disease.
AB  - Crohn's disease and ulcerative colitis are the two major forms of chronic
      relapsing inflammatory disorders of the human intestines collectively referred to
      as inflammatory bowel disease (IBD). Though a complex set of autoinflammatory
      disorders that can be precipitated by diverse genetic and environmental factors,
      a feature that appears common to IBD pathogenesis is a dysregulated effector T
      cell response to the commensal microbiota. Due to the heightened effector T cell
      activity in IBD, developmental and functional pathways that give rise to these
      cells are potential targets for therapeutic intervention. In this review, we
      highlight recent advances in our understanding of effector T cell biology in the
      context of intestinal immune regulation and speculate on their potential clinical
      significance.

PMID- 19766083
TI  - Regulatory T cells reinforce intestinal homeostasis.
AB  - Regulatory T cells help maintain intestinal homeostasis by preventing
      inappropriate innate and adaptive immune responses. CD4(+) T cells that express
      Foxp3 and Tr1-like cells that produce IL-10 comprise the major regulatory
      populations in the intestine. CD4(+)Foxp3(+) T cells play an important functional
      role in promoting tolerance of the flora and dietary proteins. Tr1-like cells can
      be generated in conditions that also promote effector T cell responses and may
      serve a similar function. In this review, we discuss the signals specific to the
      gastrointestinal tract that support both regulatory cell types and their distinct
      modes of action in the mesenteric lymph nodes and intestinal tissues.
      Dysregulation of intestinal immune homeostasis occurs in inflammatory bowel
      disease and can also be observed in graft-versus-host disease, tumor
      immunotherapy regimens, and acute HIV infection.

PMID- 19766084
TI  - Biology of lung dendritic cells at the origin of asthma.
AB  - Dendritic cells (DCs) initiate and maintain adaptive T helper 2 (Th2) cell
      responses to inhaled allergens in asthma. Various functions like antigen uptake,
      migration to the draining LNs, and induction of tolerance and adaptive immunity
      are not equally shared by all subsets of DCs, adding considerable complexity to
      understanding the immunology of allergic sensitization. Whereas the epithelium
      was initially considered solely as a physical barrier, it is now seen as a
      central player in controlling the function of lung DCs through release of Th2
      cell-promoting cytokines. Although DCs are sufficient and necessary for induction
      of Th2 cell responses to many antigens, some allergens might require antigen
      presentation by basophils. Clinically relevant allergens, as well as
      environmental and genetic risk factors for allergy and asthma, often interfere
      directly or indirectly with the innate immune functions of airway epithelial
      cells, basophils, and DCs. This review summarizes the recent progress on our
      understanding how DCs control Th2 cell immunity in the lung.

PMID- 19766086
TI  - Regulatory T cells in asthma.
AB  - Asthma is characterized by T helper cell 2 (Th2) type inflammation, leading to
      airway hyperresponsiveness and tissue remodeling. Th2 cell-driven inflammation is
      likely to represent an abnormal response to harmless airborne particles. These
      reactions are normally suppressed by regulatory T cells, which maintain airway
      tolerance. The anti-inflammatory cytokine IL-10 is likely to play a central role.
      The role of the cytokine transforming growth factor beta (TGF-beta) is more
      complex, with evidence for immune suppression and remodeling in the airways. In
      asthmatic individuals there is a breakdown in these regulatory mechanisms. There
      is emerging evidence that early life events, including exposure to allergen and
      infections, are critical in programming effective regulatory pathways to maintain
      pulmonary homeostasis. In this review we examine the clinical and experimental
      evidence for T regulatory cell function in the lung and discuss the events that
      might influence the functioning of these cells. Ultimately, the ability to
      enhance regulatory function in affected individuals may represent an effective
      treatment for asthma.

PMID- 19766085
TI  - Innate cells and T helper 2 cell immunity in airway inflammation.
AB  - Activated mast cells, eosinophils, and basophils infiltrate the airways of
      asthmatics as a result of an overexuberant T helper 2 (Th2) cell immune response
      that drives the production of IgE, primes mast cells and basophils, and promotes
      tissue eosinophilia and mast cell hyperplasia. Recent evidence demonstrates that
      these innate effectors can be activated outside of this classical Th2 cell
      paradigm and that they have additional roles in promoting the development of
      innate and adaptive pulmonary inflammation. There is also an appreciation for the
      role of airway epithelial cells in orchestrating allergic pulmonary inflammation.
      Emerging data from basic research highlight the involvement of many unique
      pathways in the inflammation triggered by complex native allergens and microbes
      at the airway mucosal surface. Here, we review the role of effector cells and
      airway epithelial cells in augmenting and, at times, bypassing traditional Th2
      cell-mediated allergic inflammation.

PMID- 19766087
TI  - Establishing the follicular helper identity.
AB  - Among other genes, expression of the Bcl-6 transcriptional repressor
      distinguishes follicular helper T (Tfh) cells from other helper T cell subsets.
      In this issue of Immunity, Yu et al. (2009) demonstrate that Bcl-6 directs Tfh
      cell differentiation.

PMID- 19766088
TI  - Diffusion and signaling revisited.
AB  - In this issue of Immunity, Andrews et al. (2009) used single-molecule
      fluorescence microscopy to demonstrate that the IgE receptor FcepsilonRI in the
      plasma membrane can signal in a mobile state.

PMID- 19766089
TI  - Before they were gut dendritic cells.
AB  - Gut lamina propria dendritic cell (DC) subsets have specialized functions. In
      this issue of Immunity, Varol et al. (2009) and Bogunovic et al. (2009) describe
      the different blood precursors for CD103(+) and CD103(-) DC subsets.

PMID- 19766090
TI  - A functional quantitative polymerase chain reaction assay for ricin, Shiga toxin,
      and related ribosome-inactivating proteins.
AB  - The potent toxins ricin, abrin, and other ribosome-inactivating proteins
      deadenylate a specific base in 28S ribosomal RNA that destroys ribosomes and
      leads to cell death. We have taken advantage of the fact that reverse
      transcriptase preferentially inserts an adenine opposite to an abasic site in RNA
      to create a quantitative polymerase chain reaction (PCR) assay to detect the
      damage. This assay detects as little as 30pg of ricin. We used the assay to study
      enzymatic properties of ricin such as pH and temperature optima (pH 4.5-5.0 and
      60 degrees C).

PMID- 19766091
TI  - Multilayer fluorescence optically encoded beads for protein detection.
AB  - An easy preparation method of multilayer fluorescence optically encoded beads for
      protein detection is presented. The beads, which consist of multicolored layers,
      are made from amino polyethylene glycol grafted polystyrene (PS-g-PEG) beads by
      using several fluorescent dyes such as fluorescein isothiocyanate (FITC) and
      rhodamine via controlling diffusion of an Fmoc-protecting group after HCl
      solution swelling. A biotin, glutathione S-transferase (GST) antibody, and an RNA
      aptamer that specifically recognize streptavidin, GST antigen, and hepatitis C
      virus (HCV) helicase are introduced to the optically encoded beads and monitored
      for their binding activity to the target molecules. After binding, the ligands
      are identified easily by their color codes.

PMID- 19766092
TI  - Characterization of two different acyl carrier proteins in complex I from
      Yarrowia lipolytica.
AB  - Acyl carrier proteins of mitochondria (ACPMs) are small (approximately 10 kDa)
      acidic proteins that are homologous to the corresponding central components of
      prokaryotic fatty acid synthase complexes. Genomic deletions of the two genes
      ACPM1 and ACPM2 in the strictly aerobic yeast Yarrowia lipolytica resulted in
      strains that were not viable or retained only trace amounts of assembled
      mitochondrial complex I, respectively. This suggested different functions for the
      two proteins that despite high similarity could not be complemented by the
      respective other homolog still expressed in the deletion strains. Remarkably, the
      same phenotypes were observed if just the conserved serine carrying the
      phosphopantethein moiety was exchanged with alanine. Although this suggested a
      functional link to the lipid metabolism of mitochondria, no changes in the lipid
      composition of the organelles were found. Proteomic analysis revealed that both
      ACPMs were tightly bound to purified mitochondrial complex I. Western blot
      analysis revealed that the affinity tagged ACPM1 and ACPM2 proteins were
      exclusively detectable in mitochondrial membranes but not in the mitochondrial
      matrix as reported for other organisms. Hence we conclude that the ACPMs can
      serve all their possible functions in mitochondrial lipid metabolism and complex
      I assembly and stabilization as subunits bound to complex I.

PMID- 19766093
TI  - Identification of the mitochondrial carrier that provides Yarrowia lipolytica
      with a fatty acid-induced and nucleotide-sensitive uncoupling protein-like
      activity.
AB  - Uncoupling proteins (UCPs) are mitochondrial carriers distributed throughout the
      eukaryotic kingdoms. While genes coding for UCPs have been identified in plants
      and animals, evidences for the presence of UCPs in fungi and protozoa are only
      functional. Here, it is reported that in the yeast Yarrowia lipolytica there is a
      fatty acid-promoted and GDP-sensitive uncoupling activity indicating the presence
      of a UCP. The uncoupling activity is higher in the stationary phase than in the
      mid-log growth phase. The in silico search on the Y. lipolytica genome led to the
      selection of two genes with the highest homology to the UCP family, XM_503525 and
      XM_500457. By phylogenetic analysis, XP_503525 was predicted to be an
      oxaloacetate carrier while XP_500457 would be a dicarboxylate carrier. Each of
      these two genes was cloned and heterologously expressed in Saccharomyces
      cerevisiae and the resulting phenotype was analyzed. The transport activity of
      the two gene products confirmed the phylogenetic predictions. In addition, only
      mitochondria isolated from yeasts expressing XP_503525 showed bioenergetic
      properties characteristic of a UCP: the proton conductance was increased by
      linoleic acid and inhibited by GDP. It is concluded that the XM_503525 gene from
      Y. lipolytica encodes for an oxaloacetate carrier although, remarkably, it also
      displays an uncoupling activity stimulated by fatty acids and inhibited by
      nucleotides.

PMID- 19766094
TI  - Differential ability of cholesterol-enriched and gel phase domains to resist
      benzyl alcohol-induced fluidization in multilamellar lipid vesicles.
AB  - Benzyl alcohol (BA) has a well-known fluidizing effect on both artificial and
      cellular membranes. BA is also likely to modulate the activities of certain
      membrane proteins by decreasing the membrane order. This phenomenon is presumably
      related to the ability of BA to interrupt interactions between membrane proteins
      and the surrounding lipids by fluidizing the lipid bilayer. The components of
      biological membranes are laterally diversified into transient assemblies of
      varying content and order, and many proteins are suggested to be activated or
      inactivated by their localization in or out of membrane domains displaying
      different physical phases. We studied the ability of BA to fluidize artificial
      bilayer membranes representing liquid-disordered, cholesterol-enriched and gel
      phases. Multilamellar vesicles were studied by steady-state fluorescence
      anisotropy of 1,6-diphenyl-1,3,5-hexatriene and trans-parinaric acid, which
      display different phase partitioning. Domains of different degree of order and
      thermal stability showed varying abilities to resist fluidization by BA. In
      bilayers composed of mixtures of an unsaturated phosphatidylcholine, a saturated
      high melting temperature lipid (sphingomyelin or phosphatidylcholine) and
      cholesterol, BA fluidized and lowered the melting temperature of the ordered and
      gel phase domains. In general, cholesterol-enriched domains were more resistant
      to BA than pure gel phase domains. In contrast, bilayers containing high melting
      temperature gel phase domains containing a ceramide or a galactosylceramide
      proved to be the most effective in resisting fluidization. The results of our
      study suggest that the ability of BA to affect the fluidity and lateral
      organization of the membranes was dependent on the characteristic features of the
      membrane compositions studied and related to the intermolecular cohesion in the
      domains.

PMID- 19766095
TI  - Mustard NPR1, a mammalian IkappaB homologue inhibits NF-kappaB activation in
      human GBM cell lines.
AB  - NF-kappaB activity is tightly regulated by IkappaB class of proteins. IkappaB
      proteins possess ankyrin repeats for binding to and inhibiting NF-kappaB. The
      regulatory protein, NPR1 from Brassica juncea possesses ankyrin repeats with
      sequence similarity to IkappaBalpha subgroup. Therefore, we examined whether
      stably expressed BjNPR1 could function as IkappaB in inhibiting NF-kappaB in
      human glioblastoma cell lines. We observed that BjNPR1 bound to NF-kappaB and
      inhibited its nuclear translocation. Further, BjNPR1 expression down-regulated
      the NF-kappaB target genes iNOS, Cox-2, c-Myc and cyclin D1 and reduced the
      proliferation rate of U373 cells. Finally, BjNPR1 decreased the levels of pERK,
      pJNK and PKCalpha and increased the Caspase-3 and Caspase-8 activities. These
      results suggested that inhibition of NF-kappaB activation by BjNPR1 can be a
      promising therapy in NF-kappaB dependent pathologies.

PMID- 19766096
TI  - Matrix elasticity regulates the secretory profile of human bone marrow-derived
      multipotent mesenchymal stromal cells (MSCs).
AB  - The therapeutic efficacy of multipotent mesenchymal stromal cells (MSCs) is
      attributed to particular MSC-derived cytokines and growth factors. As MSCs are
      applied locally to target organs or home there after systemic administration,
      they experience diverse microenvironments that are biochemically and
      biophysically distinct. Here we use well-defined in vitro conditions to study the
      impact of substrate elasticity on MSC-derived trophic factors. By varying
      hydrogel compliance, the elasticity of brain and muscle tissue was mimicked. We
      screened >90 secreted factors at the protein level, finding a diverse elasticity
      dependent expression pattern. In particular, IL-8 was up-regulated as much as 90
      fold in MSCs cultured for 2days on hard substrates, whereas levels were
      consistently low on soft substrates. In summary, we show substrate elasticity
      directly affects MSC paracrine expression, a relevant finding for therapies
      administering MSCs in vivo.

PMID- 19766097
TI  - Molecular hydrogen suppresses FcepsilonRI-mediated signal transduction and
      prevents degranulation of mast cells.
AB  - Molecular hydrogen ameliorates oxidative stress-associated diseases in animal
      models. We found that oral intake of hydrogen-rich water abolishes an immediate
      type allergic reaction in mice. Using rat RBL-2H3 mast cells, we demonstrated
      that hydrogen attenuates phosphorylation of the FcepsilonRI-associated Lyn and
      its downstream signal transduction, which subsequently inhibits the NADPH oxidase
      activity and reduces the generation of hydrogen peroxide. We also found that
      inhibition of NADPH oxidase attenuates phosphorylation of Lyn in mast cells,
      indicating the presence of a feed-forward loop that potentiates the allergic
      responses. Hydrogen accordingly inhibits all tested signaling molecule(s) in the
      loop. Hydrogen effects have been solely ascribed to exclusive removal of hydroxyl
      radical. In the immediate-type allergic reaction, hydrogen exerts its beneficial
      effect not by its radical scavenging activity but by modulating a specific
      signaling pathway. Effects of hydrogen in other diseases are possibly mediated by
      modulation of yet unidentified signaling pathways. Our studies also suggest that
      hydrogen is a gaseous signaling molecule like nitric oxide.

PMID- 19766098
TI  - Structure-function analysis of human protein Ero1-Lalpha.
AB  - Human Ero1-Lalpha catalyzes the formation of disulfide bond and hence plays an
      essential role in protein folding. Understanding the mechanism of disulfide bond
      formation in mammals is important because of the involvement of protein
      misfolding in conditions such as diabetes, arthritis, cancer, and aging. However,
      the crystal structure of the enzyme is not available yet, which seriously hinders
      the understanding of biological function of Ero1-Lalpha. Based on the crystal
      structure of yeast Ero1p, a rational three-dimensional structural model of Ero1
      Lalpha was built and the characteristics of the enzyme were hence investigated.
      The characteristic similarities and differences between Ero1-Lalpha and Ero1p
      were compared on the basis of computational and experimental results, providing
      the first insight into the structure-function relationships of the enzymes. Both
      calculation and experiment got the concordant conclusion that FAD binds more
      tightly with Ero1-Lalpha than Ero1p. In addition, the probable electron transfer
      pathway was proposed on the basis of the structural models.

PMID- 19766099
TI  - Peroxynitrite scavenging by ferryl sperm whale myoglobin and human hemoglobin.
AB  - Globins protect from the oxidative and nitrosative cell damage. Here, kinetics of
      peroxynitrite scavenging by ferryl sperm whale myoglobin (MbFe(IV)O) and human
      hemoglobin (HbFe(IV)O), between pH 5.8 and 8.3 at 20.0 degrees C, are reported.
      In the absence of CO(2), values of the second-order rate constant for
      peroxynitrite scavenging by MbFe(IV)O and HbFe(IV)O (i.e., for MbFe(III) and
      HbFe(III) formation; k(on)) are 4.6 x 10(4)M(-1)s(-1) and 3.3 x 10(4)M(-1)s(-1),
      respectively, at pH 7.1. Values of k(on) increase on decreasing pH with pK(a)
      values of 6.9 and 6.7, this suggests that the ONOOH species reacts preferentially
      with MbFe(IV)O and HbFe(IV)O. In the presence of CO(2) (=1.2 x 10(-3)M), values
      of k(on) for peroxynitrite scavenging by MbFe(IV)O and HbFe(IV)O are essentially
      pH-independent, the average k(on) values are 7.1 x 10(4)M(-1)s(-1) and 1.2 x
      10(5)M(-1)s(-1), respectively. As a whole, MbFe(IV)O and HbFe(IV)O, obtained by
      treatment with H(2)O(2), undertake within the same cycle H(2)O(2) and
      peroxynitrite detoxification.

PMID- 19766100
TI  - TNFalpha induces HIF-1alpha expression through activation of IKKbeta.
AB  - The transcription factor hypoxia-inducible factor 1alpha (HIF-1alpha) is
      regulated by oxygen availability as well as various inflammatory mediators,
      including tumor necrosis factor alpha (TNFalpha). Early work suggested that the
      phosphatidylinositol-3-kinase (PI3K) and mitogen-activated protein kinase (MAPK)
      signaling pathways are involved in TNFalpha-mediated HIF-1alpha accumulation and
      activation under normoxic conditions. Here, we provide evidence showing that
      IkappaB kinase beta (IKKbeta) is required for HIF-1alpha regulation by TNFalpha.
      We found that TNFalpha enhances HIF-1alpha protein expression in various breast
      cancer cell lines under either normoxic or hypoxia-mimicking conditions, but has
      little effect on the HIF-1alpha mRNA level. Increased HIF-1alpha expression was
      found in IKKbeta stable clones and transient transfectants, and depletion of
      IKKbeta consistently reduced the amount of HIF-1alpha protein. Treatment of cells
      with the IKKbeta inhibitor Bay 11-7082 reduced the TNFalpha-induced HIF-1alpha
      expression, suggesting that IKKbeta is required in this signaling pathway.
      Decreased expression of vascular endothelial growth factor (VEGF), a direct
      target of HIF-1alpha, was shown in IKKbeta-knockout mouse embryonic fibroblast
      cells. We further demonstrated a positive correlation between IKKbeta and VEGF
      expression in primary human breast cancer specimens. Our findings indicate that
      TNFalpha-induced HIF-1alpha accumulation is IKKbeta dependent, and may enable
      further understanding of the HIF-1alpha regulation by inflammatory signals.

PMID- 19766101
TI  - Kinase suppressor of Ras transphosphorylates c-Raf-1.
AB  - Whether kinase suppressor of Ras1 (KSR1) is an active kinase that phosphorylates
      c-Raf-1 or a scaffold that coordinates signaling along the Ras/ERK1 signaling
      module is actively debated. In this study, we generated a monoclonal antibody
      against a c-Raf-1 peptide containing phosphorylated Thr(269), the putative target
      for KSR1 kinase activity. We show that this antibody detects Thr(269)
      phosphorylated c-Raf-1 in A431 cells upon epidermal growth factor (EGF)
      stimulation, preceding MEK1 activation. Furthermore, this antibody detects in
      vitro phosphorylation of FLAG-c-Raf-1 and kinase-dead FLAG-c-Raf-1(K375M) by
      immunopurified KSR1, but fails to detect phosphorylation of FLAG-c-Raf
      1(K375M/T269V), engineered with a Thr(269) to valine substitution. To provide
      unequivocal evidence that KSR1 is a legitimate kinase, we purified KSR1 to
      homogeneity, confirmed by mass spectrometry, renatured it in-gel, and
      demonstrated that it phosphorylates BSA-conjugated c-Raf-1 peptide at Thr(269).
      These studies add to emerging data validating KSR1 as a kinase that
      phosphorylates c-Raf-1.

PMID- 19766102
TI  - Cloning and characterization of the 5'UTR of the rat anti-apoptotic Bcl-w gene.
AB  - The anti-apoptotic Bcl-w regulator, which is expressed in the developing and
      mature brain, not only promotes neuronal survival, but also neuronal
      differentiation. However, its transcriptional regulation remains to be elucidated
      due to a lack of knowledge of the Bcl-w promoter. Here, we report the mapping and
      characterization of the rat Bcl-w promoter, which is highly conserved between the
      human, mouse, and rat species. Using a series of 5' and 3' deletions, we mapped
      the TATA-less minimal Bcl-w promoter and showed that it is under a combinatorial
      regulation with the neurogenic bHLH transcription factor NeuroD6 mediating its
      activation, validating our previous finding of increased expression of the Bcl-w
      protein in stably transfected PC12-NeuroD6 cells. Upon stress, NeuroD6 promotes
      colocalization of Bcl-w with mitochondria and endoplasmic reticulum. Finally, we
      provide the first evidence of Bcl-w localization in the growth cones of
      differentiating neuronal cells, suggestive of a potential synaptic
      neuroprotective role.

PMID- 19766103
TI  - Different susceptibility of liver grafts from lean and obese Zucker rats to
      preservation injury.
AB  - We compared the susceptibility of liver grafts from lean and obese Zucker rats to
      preservation injury, using two organ-preservation techniques: conventional static
      preservation (SP) and machine perfusion (MP) preservation. SP: livers preserved
      by UW solution at 4, 8 or 20 degrees C for 6-h. MP: livers perfused for 6-h with
      an improved oxygenated Krebs-Henseleit solution (KH) at 4, 8 or 20 degrees C.
      Reperfusion with KH (2-h) was performed either with the SP or MP preserved
      livers. Fatty livers tolerate SP poorly at 4, 8 and 20 degrees C as compared with
      MP at the same temperatures. SP induced a decrease in the ATP/ADP ratio both at 8
      and 20 degrees C in obese rats while an increase in energy status was found with
      MP at 8 and 20 degrees C. Nitrate/nitrite (NOx) concentration was higher and bile
      flow lower in livers preserved with SP than MP. In lean rats, no differences were
      observed between MP and SP as regards enzyme release, bile production and NOx
      levels except for SP at 20 degrees C in which high enzyme release and low bile
      flow were observed. In lean rats ATP/ADP was higher and NOx was lower with MP at
      20 degrees C than with SP at 20 degrees C. To optimize steatotic liver
      preservation SP should be avoided because it is particularly detrimental as
      compared with MP.

PMID- 19766104
TI  - Dietary salt restriction activates mineralocorticoid receptor signaling in volume
      overloaded heart failure.
AB  - Whether a high plasma aldosterone concentration induced by strict salt
      restriction promotes cardiac remodeling remains controversial. Male Sprague
      Dawley rats at 10weeks of age were given normal salt (NS) (1.5% NaCl) or low salt
      (LS) (0.05% NaCl) diets. Each animal underwent aortocaval fistula creation for
      volume-overloaded heart failure or sham surgery. All rats with a fistula received
      either vehicle or a non-hypotensive dose of spironolactone (200mg/kg/day) by
      gavage. Two weeks later, the LS diet significantly increased the plasma
      aldosterone level in the sham-operated and fistula-created rats (2677+/-662pg/ml
      and 2406+/-422pg/ml) compared with that in rats given the NS diet (518+/-18pg/ml
      and 362+/-45pg/ml, respectively). In sham-operated rats, the difference in plasma
      aldosterone level did not affect the extent of myocardial fibrosis (1.8+/-0.1%
      with LS diet vs. 1.5+/-0.3% with NS diet). However, the increase in myocardial
      fibrosis in fistula-created rats was more prominent with the LS diet than with
      the NS diet (4.7+/-0.3% vs. 3.4+/-0.1%). In addition, the fistula-created rats on
      the LS diet expressed significantly increased oxidative stress and transforming
      growth factor-beta compared with those on the NS diets (P<0.05). These increases
      in the fistula-created rats on the LS diet were significantly suppressed by the
      non-hypotensive dose of spironolactone (P<0.05). These results suggest that
      increased plasma aldosterone level with strict salt restriction activated the
      mineralocorticoid receptor signaling in volume-overloaded condition, resulting in
      increased myocardial fibrosis.

PMID- 19766105
TI  - Differential activation of spinal microglial and astroglial cells in a mouse
      model of peripheral neuropathic pain.
AB  - The pharmacological attenuation of glial activation represents a novel approach
      for controlling neuropathic pain, but the role of microglial and astroglial cells
      is not well established. To better understand the potential role of two types of
      glial cells, microglia and astrocytes, in the pathogenesis of neuropathic pain,
      we examined markers associated with them by quantitative RT-PCR, western blot and
      immunohistochemical analyses in the dorsal horn of the lumbar spinal cord 7days
      after chronic constriction injury (CCI) to the sciatic nerve in mice. The mRNA
      and protein of microglial cells were labeled with C1q and OX42(CD11b/c),
      respectively. The mRNA and protein of astrocytes were labeled with GFAP. The RT
      PCR results indicated an increase in C1q mRNA that was more pronounced than the
      increased expression of GFAP mRNA ipsilateral to the injury in the dorsal spinal
      cord. Similarly, western blot and immunohistochemical analyses demonstrated an
      ipsilateral upregulation of OX42-positive cells (72 and 20%, respectively) and no
      or little (8% upregulation) change in GFAP-positive cells in the ipsilateral
      dorsal lumbar spinal cord. We also found that chronic intraperitoneal injection
      of the minocycline (microglial inhibitor) and pentoxifylline (cytokine inhibitor)
      attenuated CCI-induced activation of microglia, and both, but not fluorocitrate
      (astroglial inhibitor), diminished neuropathic pain symptoms and tactile and cold
      sensitivity. Our findings indicate that spinal microglia are more activated than
      astrocytes in peripheral injury-induced neuropathic pain. These findings
      implicate a glial regulation of the pain response and suggest that
      pharmacologically targeting microglia could effectively prevent clinical pain
      syndromes in programmed and/or anticipated injury.

PMID- 19766106
TI  - Presence of a putative steroidal allosteric site on glycoprotein hormone
      receptors.
AB  - In a previous work we found that the insecticide 1,1,1-trichloro-2,2-bis(p
      chlorophenyl)ethane (DDT), inhibits the accumulation of cAMP as induced by the
      bovine thyroid stimulating hormone (bTSH) in cells transfected with the TSH
      receptor. In this work, we demonstrate that the DDT molecular analogues,
      diethylstilbestrol and quercetine, are more potent inhibitors of the TSH receptor
      activity than DDT itself. The notion that all these compounds interfere with
      nuclear estrogen receptors, as either agonists (DDT and diethylstilbestrol) or
      antagonists (quercetin), prompted us to test the ability of the steroid hormone
      17-beta-estradiol to inhibit the TSH receptor activity. We found that estrogen
      exposure causes a modest but significant inhibition of the bTSH induced cAMP
      accumulation both in transfected CHO-TSH receptor and Fischer Rat Thyroid Low
      Serum 5% (FRTL-5) cells. When applied to CHO cells transfected with the
      luteinizing hormone receptor, 17-beta-estradiol proved capable of inhibiting the
      hCG induced cAMP accumulation at a concentration as low as 10nM, though the
      effect was not greater than 35%. The effect of 17-beta-estradiol was not estrogen
      receptors mediated, as co-transfection of the estrogen receptor alpha and beta
      subunits with LH receptor caused cAMP to increase above the level attained by the
      sole hCG stimulation, and not to decrease it as expected. These data suggest the
      presence of a steroidal-like allosteric binding site on glycoprotein hormone
      receptors.

PMID- 19766107
TI  - Effects of the dipeptidyl peptidase-IV inhibitor ASP8497 on glucose tolerance in
      animal models of secondary failure.
AB  - Sulfonylureas promote insulin secretion and potently lower blood glucose levels,
      however, they induce hypoglycemia and undergo a reduction in efficacy when
      administered long-term (secondary failure). The dipeptidyl peptidase (DPP)-IV
      inhibitor ASP8497, (2S,4S)-4-fluoro-1-({[4-methyl-1-(methylsulfonyl)piperidin-4
      yl]amino}acetyl)pyrrolidine-2-carbonitrile monofumarate, inhibits the degradation
      of glucagon-like peptide-1 (GLP-1), an incretin hormone, and promotes insulin
      secretion in a glucose-dependent manner. ASP8497 is therefore less likely to
      induce hypoglycemia and less likely to show reduced efficacy even after repeated
      administration. Here, to determine whether or not ASP8497 improves glucose
      tolerance in Zucker fatty rats, we examined the effects of ASP8497 and
      gliclazide, a sulfonylurea, on glucose tolerance after repeated administration.
      We also developed an animal model of secondary failure using streptozotocin
      nicotinamide-induced diabetic mice. RESULTS: ASP8497 (3mg/kg) improved glucose
      intolerance in Zucker fatty rat without any attenuation (blood glucose AUC:
      P=0.034 vs. vehicle) while gliclazide (10mg/kg) did not (P=0.916 vs. vehicle).
      Furthermore, ASP8497 (3, 10mg/kg) was found to effect glucose tolerance dose
      dependently (3mg/kg: P=0.230, 10mg/kg: P=0.003 vs. glibenclamide (10mg/kg)) by
      enhancing insulin secretion in mice inadequately controlled with glibenclamide.
      Our results suggest that ASP8497 may be effective even in patients with secondary
      failure who are unable to maintain satisfactory glycemic control using
      sulfonylureas.

PMID- 19766108
TI  - Induction of intestinal multidrug resistance-associated protein 2 (Mrp2) by
      spironolactone in rats.
AB  - The effect of spironolactone (SL) pretreatment (200micromol/kg b.w./day, 3
      consecutive days) on intestinal multidrug resistance-associated protein 2 (Mrp2)
      was evaluated in rats. A significant increase in protein levels in upper regions
      of small intestine, where Mrp2 is mainly present, was detected by western
      blotting. Real time PCR studies suggest a transcriptional regulation. The
      administration of ketoconazole, a pregnane X receptor (PXR) antagonist, was able
      to prevent the increase in Mrp2 mRNA levels induced by SL. The serosal to mucosal
      transport of dinitrophenyl S-glutathione, a model substrate of Mrp2 was evaluated
      in jejunal sac model. The data indicate that SL increased Mrp2 activity, well
      correlating with its up-regulation. We conclude that SL is able to induce
      intestinal Mrp2 transcriptionally, PXR being a potential mediator. We propose
      that SL could be of potential therapeutic application particularly in situations
      of down-regulation of intestinal Mrp2.

PMID- 19766109
TI  - Effects of the prototype serotonin 5-HT(1B/1D) receptor agonist sumatriptan and
      the calcitonin gene-related peptide (CGRP) receptor antagonist CGRP(8-37) on
      myocardial reactive hyperemic response in conscious dogs.
AB  - The triptans, serotonin 5-HT(1B/1D) receptor agonists exemplified by sumatriptan,
      are a mainstay migraine therapy but have class labeling contraindicating their
      use in patients with coronary artery disease. Triptans constrict human coronary
      artery in vitro, and there are case reports of myocardial infarction in patients
      using sumatriptan. However, preclinical studies with sumatriptan in normal dogs
      have failed to demonstrate effects on resting coronary flow. Calcitonin gene
      related peptide (CGRP) receptor antagonism, exemplified by the prototype CGRP
      receptor antagonist peptide CGRP(8-37), is a new antimigraine mechanism which
      also has been reported to have no effect on coronary flow in normal, non-stressed
      animals. The goal of the present studies was to compare the effects of
      sumatriptan (10microg/kg/min i.v.) and CGRP(8-37) (30microg/kg/min i.v.) on
      systemic and coronary hemodynamics in conscious dogs under resting conditions and
      during myocardial reactive hyperemia following a brief 15s of coronary artery
      occlusion. Neither CGRP(8-37) nor sumatriptan affected resting coronary flow.
      However, whereas CGRP(8-37) had no effect on myocardial reactive hyperemic
      response, sumatriptan reduced peak reactive hyperemic coronary artery blood flow
      (baseline vs treatment: 75.4+/-12.7 vs 60.0+/-10.3ml/min, P<0.05), reactive
      hyperemic flow (16.7+/-5.2 vs 11.6+/-3.3ml, P<0.05) and the repayment of coronary
      blood flow debt following coronary artery occlusion (484+/-76 vs 369+/-57%,
      P<0.05), indicating an impairment in coronary blood flow reserve. The positive
      control nitric oxide synthase inhibitor L-NNA (30mg/kg/30min i.v.) likewise
      significantly attenuated myocardial reactive hyperemic response. These findings
      provide evidence for a differentiation between CGRP receptor antagonism and
      triptan effects on coronary vascular function.

PMID- 19766110
TI  - Enhanced effect of neuropeptide Y on food intake caused by blockade of the V(1A)
      vasopressin receptor.
AB  - Food intake is regulated by various factors such as neuropeptide Y. Neuropeptide
      Y potently induces an increase in food intake, and simultaneously stimulates
      arginine-vasopressin (AVP) secretion in the brain. Recently, we reported that
      V(1A) vasopressin receptor-deficient (V(1A)R(-/-)) mice exhibited altered daily
      food intake accompanied with hyperglycemia and hyperleptinemia. Here, we further
      study the involvement of the AVP/V(1A) receptor in the appetite regulation of
      neuropeptide Y with V(1A)R(-/-) mice and antagonists for the AVP receptor. The
      intra-cerebral-ventricle administration of neuropeptide Y induced greater food
      consumption in V(1A)R(-/-) mice than wild-type (WT) mice, whereas an anorexigenic
      effect of leptin was not different between the two groups. This finding suggests
      that the orexigenic effect of neuropeptide Y was enhanced in V(1A)R(-/-) mice,
      leading to the increased food intake in response to the neuropeptide Y
      stimulation. In addition, the neuropeptide Y-induced orexigenic effect was
      enhanced by co-administration of OPC-21268, an antagonist for the V(1A)
      vasopressin receptor, into the cerebral ventricle in WT mice, whereas the
      neuropeptide Y-induced orexigenic effect was not affected by co-administration of
      SSR-149415, an antagonist for the V(1B) vasopressin receptor. These results
      indicate that AVP could suppress the neuropeptide Y-induced orexigenic effect via
      the V(1A) vasopressin receptor, and that blockade or inhibition of the AVP/V(1A)
      receptor signal resulted in the enhanced neuropeptide Y-induced orexigenic
      effect. Thus, we show that the AVP/V(1A) receptor is involved in appetite
      regulation as an anorexigenic factor for the neuropeptide Y-induced orexigenic
      effect.

PMID- 19766111
TI  - Trichostatin A inhibits osteoclastogenesis and bone resorption by suppressing the
      induction of c-Fos by RANKL.
AB  - Histone deacetylases are enzymes involved in the remodeling of chromatin
      structure, in the regulation of transcriptional activity, and in epigenetic
      integrity. Histone deacetylase inhibitors such as trichostatin A (TSA) and
      suberoylanilide hydroxamic acid (SAHA) have emerged as potent anticancer drugs
      that have proved useful in preclinical and early clinical trials. The role of
      histone deacetylase inhibitors in regulating osteoclast differentiation, however,
      is not well established. In this study, we analyzed the effects of TSA on
      osteoclast differentiation induced by the differentiation factor RANKL (receptor
      activator of NF-kappaB ligand). TSA strongly inhibited osteoclast formation in
      coculture of bone marrow cells and osteoblasts without reducing RANKL expression
      in osteoblasts. Furthermore, TSA suppressed RANKL-induced osteoclast formation
      from primary bone marrow-derived macrophages. TSA was only effective when present
      during the early stage of osteoclast differentiation. This effect was accompanied
      by a significant decrease in the RANKL-stimulated induction of c-Fos and NFATc1,
      which are key transcription factors during early osteoclastogenesis. The ectopic
      introduction of c-Fos and a constitutively active form of NFATc1 reversed the TSA
      induced antiosteoclastogenic effect. Consistent with the in vitro results, TSA
      inhibited lipopolysaccharide- and interleukin-1-induced bone resorption and
      osteoclast formation in an in vivo model. Taken together, our findings suggest a
      novel action of TSA: inhibiting RANKL-induced osteoclast formation by suppressing
      the induction of the osteoclastogenic transcription factor c-Fos. Also, the
      inhibitory effect of TSA on bone destruction in vivo suggests that histone
      deacetylase inhibitors may be novel therapeutics for treating typical bone
      diseases.

PMID- 19766112
TI  - Stimulation of ceramide formation and suicidal erythrocyte death by vitamin K(3)
      (menadione).
AB  - Vitamin K(3) is an essential micronutrient required for the activation of
      coagulation factors and thus hemostasis. Administration of vitamin K(3) analogues
      may cause anemia, which at least in theory could be due to stimulation of
      suicidal erythrocyte death or eryptosis characterized by cell shrinkage and
      phospholipid scrambling of the erythrocyte cell membrane leading to exposure of
      phosphatidylserine at the erythrocyte surface. Eryptosis is triggered by an
      increase in the cytosolic Ca(2+) activity, by ceramide and by energy depletion
      (decrease of cytosolic ATP). The present experiments explored, whether vitamin
      K(3) may influence eryptosis. Hemolysis was estimated from the supernatant
      hemoglobin concentration, phosphatidylserine-exposing erythrocytes from annexin V
      binding in fluorescence-activated cell sorter (FACS) analysis, erythrocyte volume
      from forward scatter in FACS analysis, ceramide formation from binding of
      fluorescent antibodies, and erythrocyte ATP content from a luciferin-luciferase
      assay. As a result, vitamin K(3) (> or =1microM) caused lysis of an only small
      fraction of erythrocytes, but significantly increased ceramide formation,
      significantly increased the percentage of annexin V-binding erythrocytes,
      significantly decreased forward scatter and, at higher concentrations,
      significantly decreased the cellular ATP content. In conclusion, vitamin K(3)
      stimulates suicidal erythrocyte death, an effect at least partially due to
      ceramide formation and ATP depletion.

PMID- 19766113
TI  - MMR/c-Abl-dependent activation of ING2/p73alpha signaling regulates the cell
      death response to N-methyl-N'-nitro-N-nitrosoguanidine.
AB  - Agents inducing O(6)-methylguanine (O(6)MeG) in DNA such as N-methyl-N'-nitro-N
      nitrosoguanidine (MNNG) are cytotoxic and a deficiency in mismatch repair (MMR)
      results in lack of sensitivity to this genotoxin (termed alkylation tolerance).
      Here, we show that ING2, a member of the inhibitor of growth family, is required
      for cell death induced by MNNG. We further observe that MNNG treatment increases
      cellular protein levels of ING2 that is dependent on intact MMR function and that
      MNNG-induced ING2 localizes and associates with p73alpha in the nucleus.
      Suppression of ING2 by short hairpin RNA (shRNA) in MMR-proficient colorectal
      cancer cells decreased its sensitivity to MNNG and, in addition, abrogated MNNG
      induced stabilization and acetylation of p73alpha. Interestingly, suppression of
      p73alpha had a greater impact on MNNG-induced cell death than ING2 leading us to
      conclude that ING2 regulates the cell death response, in part, through p73alpha.
      Inhibition of c-Abl by STI571 or suppression of c-Abl expression by shRNA blocked
      ING2 induction and p73alpha acetylation induced by this alkylator. Similarly,
      suppression of MMR (MLH1) by shRNA abrogated ING2 induction/p73alpha acetylation.
      Taken together, these results demonstrate that MLH1/c-Abl-dependent activation of
      ING2>p73alpha signaling regulates cell death triggered by MNNG and further
      suggests that dysregulation of this event may, in part, be responsible for
      alkylation tolerance observed in MMR compromised cells.

PMID- 19766114
TI  - TGF-beta enforces senescence in Myc-transformed hematopoietic tumor cells through
      induction of Mad1 and repression of Myc activity.
AB  - Inhibition of tumor growth factor (TGF)-beta-mediated cell cycle exit is
      considered an important tumorigenic function of Myc oncoproteins. Here we found
      that TGF-beta1 enforced G(1) cell cycle arrest and cellular senescence in human U
      937 myeloid tumor cells ectopically expressing v-Myc, which contains a
      stabilizing mutation frequently found in lymphomas. This correlated with induced
      expression of the Myc antagonist Mad1, resulting in replacement of Myc for Mad1
      at target promoters, reduced histone acetylation and strong repression of Myc
      driven transcription. The latter was partially reversed by histone deacetylase
      (HDAC) inhibitors, consistent with involvement of Mad1. Importantly, knockdown of
      MAD1 expression prevented TGF-beta1-induced senescence, underscoring that Mad1 is
      a crucial component of this process. Enforced Mad1 expression sensitized U-937
      myc cells to TGF-beta and restored phorbol ester-induced cell cycle exit, but
      could not alone induce G(1) arrest, suggesting that Mad1 is required but not
      sufficient for cellular senescence. Our results thus demonstrate that TGF-beta
      can override Myc activity despite a stabilizing cancer mutation and induce
      senescence in myeloid tumor cells, at least in part by induction of Mad1. TGF
      beta-induced senescence, or signals mimicking this pathway, could therefore
      potentially be explored as a therapeutic principle for treating hematopoietic and
      other tumors with deregulated MYC expression.

PMID- 19766115
TI  - Loss of retinal capillary vasoconstrictor response to Endothelin-1 following
      pressure increments in living isolated rat retinas.
AB  - Increased intraocular pressure (IOP) is a major risk factor for glaucoma, and its
      contribution to neuronal damage appears multi-factorial. An open issue is whether
      pressure effects on blood vessels contribute to neuronal damage. In particular,
      little is known about pressure effects on capillaries, which are the site of most
      metabolic exchange in the retina, but cannot be easily visualized in vivo. To
      address this issue, here we have imaged retinal capillaries in acutely isolated
      living rat retinas, and measured alterations in capillary viability, caliber and
      response to vasoactive stimuli after controlled pressure stimuli. We found that
      capillary viability, diameter and response to vasodilator stimulation are not
      affected after pressure increments; yet, a prolonged lack of capillary response
      to the vasoconstrictor Endothelin-1 (Et-1) is observed. Considering that Et-1 is
      a major component of the endogenous control of retinal blood flow the present
      data lead to the hypothesis that prolonged or repeated IOP elevation could induce
      capillary disregulation contributing to neuronal damage over time.

PMID- 19766116
TI  - Spatiotemporal aspects of pulsed electrical stimuli on the responses of rabbit
      retinal ganglion cells.
AB  - Implanted intraocular microelectrode arrays are being used to provide sight to
      individuals who are blind due to photoreceptor degeneration. It is envisioned
      that this retinal prosthesis will create the illusion of motion by stimulating
      focal areas of the retina in a sequential fashion through neighboring electrodes,
      much like the rapid succession of still images in movies and computer animation
      gives rise to apparent motion. Using a high-density microelectrode array, we
      examined the extracellularly recorded responses of rabbit retinal ganglion cells
      to a bar-shaped electrode array that was stepped at 50 microm increments at
      different rates across the retina and compared these responses to the responses
      generated to a similarly shaped light stimulus that was stepped across the
      retina. When the retina was stimulated at 1 step/s, retinal ganglion cells gave
      robust bursts of action potentials to both the electrode array and the light
      stimulus. The responses to the 'moving' electrode array decreased progressively
      with increasing stepping frequency. At 16 steps/s (highest frequency tested), the
      number of spikes per sweep and the number of bursts per sweep were reduced 75%
      and 67% respectively. In contrast, when the retina was stimulated at 16 steps/s
      with the 'moving' light stimulus, the number of spikes per sweep and the number
      of bursts per sweep were reduced only 43% and 25% respectively. These findings
      suggest that simple translation of object motion to sequential stimulation
      through neighboring electrodes may not be the best way to convey the perception
      of object motion in a patient with a retinal prosthesis.

PMID- 19766117
TI  - Overexpression of human selenoprotein H in neuronal cells ameliorates ultraviolet
      irradiation-induced damage by modulating cell signaling pathways.
AB  - Selenoprotein H (SelH) is one of the 25 so far identified selenoproteins.
      Selenoproteins may function as antioxidants, heavy metal antidotes, and neural
      survival factors. Previous studies have shown that overexpression of SelH in HT22
      cells protected the cells from UVB irradiation-induced death by reducing
      superoxide formation. The objective of this study was to determine the effects of
      SelH on cell signaling pathways after UVB irradiation. We exposed both human SelH
      and vector-transfected HT22 cells to UVB irradiation and collected samples at 5
      and 17 h of recovery. Cell viability was assessed, as well as protein levels of
      caspase-3, -8, -9, apoptosis-inducing factor (AIF), P53, nuclear respiratory
      factor-1 (NRF-1) and heat shock protein 40 (HSP40). Mitochondrial membrane
      potential was determined by flow cytometry. Overexpression of SelH protected
      cells against UVB-induced injury by blockade of the mitochondria-initiated cell
      death pathway, prevention of mitochondrial membrane depolarization, and
      suppression of the increase of p53. Furthermore, overexpression of SelH increased
      levels of NRF-1, an antioxidant, and HSP40, a protein chaperone that repairs
      denatured protein. We conclude that SelH protects neurons against UVB-induced
      damage by inhibiting apoptotic cell death pathways, by preventing mitochondrial
      depolarization, and by promoting cell survival pathways.

PMID- 19766118
TI  - A role for galectin-1 in the immune response to peripheral nerve injury.
AB  - Galectin-1 (Gal1) is a multi-functional protein that has key roles in organismal
      growth and survival. In the adult nervous system, Gal1 promotes axonal
      regeneration following peripheral nerve injury. Although the mechanism by which
      Gal1 promotes regeneration is unclear, previous reports suggested that Gal1 acts
      indirectly by activating macrophages. An appropriate response of macrophages is
      crucial for repair of injured nerves: these immune cells remove obstructive axon
      and myelin debris in the distal nerve. Here we establish a role for Gal1 in the
      accumulation of immune cells following peripheral axotomy. We used
      immunohistochemistry to visualize macrophages (F4/80) in wild-type (Lgals1(+/+))
      and knockout (Lgals1(-/-)) mouse sciatic nerves following injury and/or
      manipulation of Gal1 levels. Density of F4/80 immunoreactivity, which peaks
      around 3 days post-injury, was decreased in Lgals1(+/+) nerves injected with Gal1
      antibody. The typical injury-induced peak of macrophage/microglial density was
      delayed in the sciatic nerves and fifth lumbar dorsal root ganglia of Lgals1(-/-)
      mice relative to control mice. Injection of oxidized Gal1 into uninjured sciatic
      nerve promoted the accumulation of macrophages in Lgals1(+/+) nerves. Finally, we
      used transplants of sciatic nerve to uncover a compensatory mechanism in Lgals1(
      /-) mice that allows for macrophage accumulation (albeit delayed and diminished)
      following axotomy. We conclude that Gal1 is necessary to direct the typical
      accumulation of macrophages in the injured peripheral nerve, and that Gal1 is
      sufficient to promote macrophage accumulation in the uninjured nerve of wild-type
      mice.

PMID- 19766119
TI  - A conditioning lesion induces changes in gene expression and axonal transport
      that enhance regeneration by increasing the intrinsic growth state of axons.
AB  - Injury of axons in the peripheral nervous system (PNS) induces transcription
      dependent changes in gene expression and axonal transport that promote effective
      regeneration by increasing the intrinsic growth state of axons. Regeneration is
      enhanced in axons re-injured 1-2 weeks after the intrinsic growth state has been
      increased by such a prior conditioning lesion (CL). The intrinsic growth state
      does not increase after axons are injured in the mammalian central nervous system
      (CNS), where they lack the capacity for effective regeneration. Sensory neurons
      in the dorsal root ganglion (DRG) have two axonal branches that respond
      differently to injury. Peripheral branches, which are located entirely in the
      PNS, are capable of effective regeneration. Central branches regenerate in the
      PNS (i.e., in the dorsal root, which extends from the DRG to the spinal cord),
      but not in the CNS (i.e., the spinal cord). A CL of peripheral branches increases
      the intrinsic growth state of central branches in the dorsal columns of the
      spinal cord, enabling these axons to undergo lengthy regeneration in a segment of
      peripheral nerve transplanted into the spinal cord (i.e., a peripheral nerve
      graft). This regeneration does not occur in the absence of a CL. We will examine
      how changes in gene expression and axonal transport induced by a CL may promote
      this regeneration.

PMID- 19766120
TI  - A new species and record of branchial parasitic isopods (Crustacea: Isopoda:
      Bopyridae: Pseudioninae) of porcellanid crabs from the Philippines.
AB  - Branchial bopyrids infesting porcellanid crabs from the Philippines were
      investigated based on intertidal collections made in 1999-2000. Crabs of the
      genus Petrolisthes collected from sites in the northern Philippines were examined
      and two parasite species were found. One new pseudionine species found infesting
      Petrolisthes sp. [cf. Petrolisthes asiaticus (Leach)] is described as
      Aporobopyrus galleonus (prevalence 6.1%); this species is distinguished from
      other members of the genus by a setose palp on the maxilliped of the females,
      barbula morphology, and male characters including the possession of pleopods.
      This represents the second described species of Aporobopyrus from the
      Philippines, and the first from porcellanid crabs. In addition, Pleurocrypta
      macrocephala Nierstrasz and Brender a Brandis, 1923 (originally described from
      Indonesia) was found infesting the same unidentified Petrolisthes sp. (prevalence
      2.6%); this is the first report of the species from the Philippines.

PMID- 19766121
TI  - Activation of the black seabream (Acanthopagrus schlegeli) somatolactin-alpha
      gene promoter by Pit-1c in the Hepa-T1 cell-line.
AB  - Somatolactin (SL) is a pituitary hormone of the growth hormone (GH) gene family
      found only in fish. To understand the regulation of this hormone at the level of
      gene transcription, we obtained a SLalpha gene from black seabream (bsb), with
      its 5' flanking promoter region carrying several putative transcription factors
      including seven binding sites for pituitary-specific transcription factor 1 (Pit
      1). To study the actions of Pit-1 on this gene promoter, we cloned three variants
      of bsbPit-1 (Pit-1a, Pit-1b and Pit-1c) derived from alternative splicing of mRNA
      or differential transcription start sites from black seabream pituitary. The
      deduced amino acid sequences of these Pit-1s contained 371 amino acids (aa), 333
      and 311aa for the three Pit-1 variants, Pit-1a, Pit-1b and Pit-1c, respectively,
      with diverse regions of Pit-1 located at the transactivation domain. The actions
      of bsbPit-1 variants on the bsbSL gene promoter were investigated using a co
      transfection assay, with a reporter gene using a transient expression assay in
      Hepa-T1 cells. The N-terminus truncated isoform bsbPit-1c showed the highest
      level of activity on SLalpha gene promoter activation in Hepa-T1 cells; however,
      neither Pit-1a nor Pit-1b activated the bsbSL gene promoter in the same study.

PMID- 19766122
TI  - Measurements of Cry1F binding and activity of luminal gut proteases in
      susceptible and Cry1F resistant Ostrinia nubilalis larvae (Lepidoptera:
      Crambidae).
AB  - The biochemical mechanism of resistance to the Bacillus thuringiensis Cry1F toxin
      was studied in a laboratory-selected strain of Ostrinia nubilalis (Hubner)
      (Lepidoptera: Crambidae) showing more than 3000-fold resistance to Cry1F and
      limited cross resistance to other Cry toxins. Analyses of Cry1F binding to brush
      border membrane vesicles of midgut epithelia from susceptible and resistant
      larvae using ligand immunoblotting and Surface Plasmon Resonance (SPR) suggested
      that reduced binding of Cry1F to insect receptors was not associated with
      resistance. Additionally, no differences in activity of luminal gut proteases or
      altered proteolytic processing of the toxin were observed in the resistant
      strain. Considering these results along with previous evidence of relatively
      narrow spectrum of cross resistance and monogenic inheritance, the resistance
      mechanism in this Cry1F selected strain of O. nubilalis appears to be specific
      and may be distinct from previously identified resistance mechanisms reported in
      other Lepidoptera.

PMID- 19766123
TI  - Reconstitution and engineering of apoptotic protein interactions on the bacterial
      cell surface.
AB  - The interactions between pro- and anti-apoptotic members of the Bcl-2 class of
      proteins control whether a cell lives or dies, and the study of these protein
      protein interactions has been an area of intense research. In this report, we
      describe a new tool for the study and engineering of apoptotic protein
      interactions that is based on the flow cytometric detection of these interactions
      on the surface of Escherichia coli. After validation of the assay with the well
      studied interaction between the Bak(72-87) peptide and the anti-apoptotic protein
      Bcl-x(L), the effect of both increasing and decreasing Bak peptide length on Bcl
      x(L) binding was investigated. Previous work demonstrated that the Bak(72-87)
      peptide also binds to the anti-apoptotic protein Bcl-2, albeit with lower binding
      affinity compared to Bcl-x(L). Here, we demonstrate that a slightly longer Bak
      peptide corresponding to amino acids 72-89 of Bak binds Bcl-x(L) and Bcl-2
      equally well. Approximate binding affinity calculations on these peptide-protein
      complexes confirm the experimental observations. The flow cytometric assay was
      also used to screen a saturation mutagenesis library of Bak(72-87) variants for
      improved affinity to Bcl-x(L). The best variants obtained from this library
      exhibit an apparent K(d) to Bcl-x(L) 4-fold lower than that of wild-type Bak(72
      87).

PMID- 19766124
TI  - A computational model of intussusceptive microvascular growth and remodeling.
AB  - Non-sprouting angiogenesis, also known as intussusceptive angiogenesis (IA), is
      an important modality of blood vessel morphogenesis in growing tissues. We
      present a novel computational framework for simulation of IA to answer some of
      the questions concerning the underlying mechanisms of the remodeling process. The
      model relies on mechanical interactions between blood and tissue, includes the
      structural maturation of the vessel wall, and is controlled by stimulating or
      inhibiting chemical agents. The model provides a simple explanation for the
      formation of microvessels and bifurcations from capillaries via IA, allowing for
      both maintenance and avoidance of shunt vessels. Detailed hemodynamic and
      transport properties for oxygen, metabolites or growth factors can be predicted.
      The model is an in silico framework for testing certain conceptual ideas about
      the mechanisms of intussusceptive growth and remodeling, in particular those
      related to mechanical and transport phenomena.

PMID- 19766125
TI  - Model of the cAMP activation of chloride transport by CFTR channel and the
      mechanism of potentiators.
AB  - Mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) cause
      cystic fibrosis, a hereditary lethal disease. CFTR is a chloride channel
      expressed in the apical membrane of epithelia. It is activated by cAMP dependent
      phosphorylation and gated by the binding of ATP. The impaired chloride transport
      of some types of cystic fibrosis mutations could be pharmacologically solved by
      the use of chemical compounds called potentiators. Here it is undertaken the
      construction of a model of the CFTR activation pathways, and the possible
      modification produced by a potentiator application. The model yields a novel
      mechanism for the potentiator action, describing the activatory and inhibitory
      activities on two different positions in the CFTR activation pathway.

PMID- 19766126
TI  - The effect of intrinsic stochasticity on transmitted HIV drug resistance
      patterns.
AB  - Estimates of transmitted HIV drug-resistance prevalence vary widely among and
      within epidemiological surveys. Interpretation of trends from available survey
      data is therefore difficult. Because the emergence of drug-resistance involves
      small populations of infected drug-resistant individuals, the role of
      stochasticity (chance events) is likely to be important. The question addressed
      here is: how much variability in transmitted HIV drug-resistance prevalence
      patterns arises due to intrinsic stochasticity alone, i.e., if all starting
      conditions in the different epidemics surveyed were identical? This 'thought
      experiment' gives insight into the minimum expected variabilities within and
      among epidemics. A simple stochastic mathematical model was implemented. Our
      results show that stochasticity alone can generate a significant degree of
      variability and that this depends on the size and variation of the pool of new
      infections when drug treatment is first introduced. The variability in
      transmitted drug-resistance prevalence within an epidemic (i.e., the temporal
      variability) is large when the annual pool of all new infections is small (fewer
      than 200, typical of the HIV epidemics in Central European and Scandinavian
      countries) but diminishes rapidly as that pool grows. Epidemiological surveys
      involving hundreds of new infections annually are therefore needed to allow
      meaningful interpretation of temporal trends in transmitted drug-resistance
      prevalence within individual epidemics. The stochastic variability among
      epidemics shows a similar dependence on the pool of new infections if treatment
      is introduced after endemic equilibrium is established, but can persist even when
      there are more than 10,000 new infections annually if drug therapy is introduced
      earlier. Stochastic models may therefore have an important role to play in
      interpreting differences in transmitted drug-resistance prevalence trends among
      epidemiological surveys.

PMID- 19766127
TI  - Effect of particle collisions and aggregation on red blood cell passage through a
      bifurcation.
AB  - Blood flow through bifurcating vessels in the microvasculature leads to uneven
      distribution of red blood cells (RBC) in the downstream channels when the
      channels have different sizes or the flow rates through the channels are
      different. This phenomenon, known as plasma skimming, is responsible for the
      large variation in hematocrit throughout the circulatory system. Furthermore, the
      strong streamline curvature present within bifurcations leads to frequent
      collisions between the blood elements (red and white blood cells and platelets)
      and the vessel walls, as well as a rearrangement of the distribution of the blood
      elements in the channels downstream of the bifurcation. Computational models of
      bifurcation flows typically neglect collision and adhesion of RBCs with each
      other. In this paper, we use a new type of discrete-element model to investigate
      the effect of particle-particle collisions and RBC aggregation on modeling of
      plasma skimming in bifurcations. Cases are examined with and without RBC adhesion
      and for different hematocrit values, including validation against previous
      computational results. Results show significant plasma skimming in the low-flow
      daughter branch and an increase in fractional particle flux with increased
      hematocrit, as in experimental studies. Accounting for particle-particle
      collisions leads to a considerable increase in collision rate of particles with
      the vessel wall. Particles are found to approximately follow fluid velocity
      streamlines, and consequently particle-particle collisions and aggregation do not
      significantly affect plasma skimming.

PMID- 19766129
TI  - Grammatical processing in schizophrenia: evidence from morphology.
AB  - Patients with psychiatric disorders such as schizophrenia commonly present with
      impaired language. Here we investigate language in schizophrenia with a focus on
      inflectional morphology, using an intensively studied and relatively well
      understood linguistic paradigm. Patients with schizophrenia (n=43) and age
      matched healthy control subjects (n=42) were asked to produce past tenses of
      regular (slip), irregular (swim), and novel (plag) English verbs. Patients were
      impaired at regulars and novels (slipped, plagged), with relative sparing of
      irregulars (swam), controlling for numerous subject- and item-specific factors
      (e.g., IQ, phonological complexity). Additionally, patients' thought-disorder
      scores significantly predicted their performance at regular and novel (but not
      irregular) past-tense production. The results support grammatical deficits in
      schizophrenia, with a relative sparing of lexical memory, and suggest that
      thought disorder may be linked with grammatical impairments in the disorder.

PMID- 19766130
TI  - Disruption to higher order processes in Friedreich ataxia.
AB  - Friedreich ataxia (FRDA), the most common of the genetically inherited ataxias,
      is characterised by ocular motor deficits largely reflecting disruption to
      brainstem-cerebellar circuitry. These deficits include fixation instability,
      saccadic dysmetria, disrupted pursuit, and vestibular abnormalities. Whether
      higher order or cognitive control processes involved the generation of more
      volitional eye movements are similarly impaired, has not been explored
      previously. This research examined antisaccade and memory-guided saccade
      characteristics in 13 individuals with genetically confirmed FRDA, and contrasted
      performance with neurologically healthy individuals. We demonstrate, for the
      first time, a broad range of deficits in FDRA consistent with disruption to
      higher order processes involved in the control of saccadic eye movement.
      Significant differences between FDRA and control participants were revealed
      across all movement parameters (latency, gain, velocity, position error), and
      across all saccade types, including alterations to velocity profiles. FDRA
      participants also generated significantly more erroneous responses to non-target
      stimuli in both saccade paradigms. Finally, a number of correlations between
      ocular motor and clinical measures were revealed including those between contrast
      acuity and saccadic latency (all saccade types), disease duration and measures of
      response inhibition (errors and relative latencies for antisaccades), and
      neurological scores and error latencies, arguably a reflection of difficulty
      resolving response conflict. These results suggest a role for the cerebellum in
      higher order cognitive control processes, and further support the proposal that
      eye movement markers, which can be measured with accuracy and reliability, may be
      a useful biomarker in FDRA.

PMID- 19766128
TI  - Genotype to phenotype: analyzing the effects of inherited mutations in colorectal
      cancer families.
AB  - With improvements to DNA sequencing technologies, including the advent of
      massively parallel sequencing to perform "deep sequencing" of tissue samples, the
      ability to determine all of the nucleotide variations in a tumor becomes a
      possibility. This information will allow us to more fully understand the
      heterogeneity within each tumor, as well as to identify novel genes involved in
      cancer development. However, the new challenge that arises will be to interpret
      the pathogenic significance of each genetic variant. The enormity and complexity
      of this challenge can be demonstrated by focusing on just the genes involved in
      the hereditary colon cancer syndromes, familial adenomatous polyposis (FAP) and
      hereditary non-polyposis coli (HNPCC). The genes responsible for each disease
      were identified almost two decades ago -APC for FAP and the MMR genes for HNPCC -
      and a large number of germline variations have been identified in these genes in
      hereditary cancer patients. However, relating the effect of an individual
      genotype to phenotype is not always straightforward. This review focuses on the
      roles of the APC and MMR genes in tumor development and the work that has been
      done to relate different variants in each gene to functional aberrations and
      ultimately tumorigenesis. By considering the work that has already been done on
      two well-defined diseases with clear genetic associations, one can begin to
      understand the challenges that lie ahead as new genes and gene mutations are
      discovered through tumor sequencing.

PMID- 19766131
TI  - Impaired grasping in a patient with optic ataxia: primary visuomotor deficit or
      secondary consequence of misreaching?
AB  - Optic ataxia is defined as a spatial impairment of visually guided reaching, but
      it is typically accompanied by other visuomotor difficulties, notably a failure
      to scale the handgrip appropriately while reaching to grasp an object. This
      impaired grasping might reflect a primary visuomotor deficit, or it might be a
      secondary effect arising from the spatial uncertainty associated with poor
      reaching. To distinguish between these possibilities, we used a new paradigm to
      tease apart the proximal and distal components of prehension movements. In the
      "far" condition objects were placed 30 cm from the hand so that subjects had to
      make a reaching movement to grasp them, whereas in the "close" condition objects
      were placed adjacent to the hand, thereby removing the need for a reaching
      movement. Stimulus eccentricity was held constant. We tested a patient with optic
      ataxia (M.H.), whose misreaching affects only his right hand within the right
      visual hemifield. M.H. showed a clear impairment in grip scaling, but only when
      using his right hand to grasp objects in the right visual hemifield. Critically,
      this grip-scaling impairment was absent in M.H. in the "close" condition. These
      data suggest that M.H.'s grip scaling is impaired as a secondary consequence of
      making inaccurate reaching movements, and not because of any intrinsic visuomotor
      impairment of grasping. We suggest that primary misgrasping is not a core symptom
      of the optic ataxia syndrome, and that patients will show a primary deficit only
      when their lesion extends anteriorly within the intraparietal sulcus to include
      area aIPS.

PMID- 19766132
TI  - Sodium arsenite alters cell cycle and MTHFR, MT1/2, and c-Myc protein levels in
      MCF-7 cells.
AB  - There is limited available information on the effects of arsenic on enzymes
      participating in the folate cycle. Therefore, our aim was to evaluate the effects
      of sodium arsenite on the protein levels of methylenetetrahydrofolate reductase
      (MTHFR) and dihydrofolate reductase (DHFR) and its further relationship with the
      expression MT1/2 and c-myc in MCF-7 cells. Arsenite treatment (0-10 microM) for 4
      h decreased MTHFR levels in a concentration-dependent fashion without significant
      effects on DHFR. The effects on MTHFR were observed at arsenite concentrations
      not significantly affecting cell viability. We also observed an increase in S
      phase recruitment at all concentrations probed. Lower concentrations (<5 microM)
      induced cell proliferation, showing a high proportion of BrdU-stained cells,
      indicating a higher DNA synthesis rate. However, higher concentrations (> or =5
      microM) or longer treatment periods induced apoptosis. Arsenite also induced dose
      dependent increases in MT1/2 and c-Myc protein levels. The levels of MTHFR were
      inversely correlated to MT1/2 and c-Myc overexpression and increased S-phase
      recruitment. Our findings indicate that breast epithelial cells are responsive to
      arsenite and suggest that exposure may pose a risk for breast cancer. The
      reductions in MTHFR protein levels contribute to understand the mechanisms
      underlying the induction of genes influencing growth regulation, such as c-myc
      and MT1/2. However, further research is needed to ascertain if the effects here
      reported following short-time and high-dose exposure are relevant for human
      populations chronically exposed to low arsenic concentrations.

PMID- 19766133
TI  - Behavioral and neurochemical effects of amphetamine analogs that release
      monoamines in the squirrel monkey.
AB  - To date, there are no effective pharmacotherapies for treating psychostimulant
      abuse. Previous preclinical and clinical studies have shown that continuous
      treatment with the monoamine releaser amphetamine reduces cocaine self
      administration, but amphetamine selectively targets the dopamine system and is
      reinforcing. In the present study, we examined the consequences of administration
      of amphetamine and three structurally related analogs that vary in their
      potencies for releasing dopamine and serotonin on behavioral-stimulant effects
      and nucleus accumbens dopamine levels in squirrel monkeys. Amphetamine and PAL
      353, which have relatively high selectivity for releasing dopamine vs. serotonin,
      increased accumbens dopamine levels and induced stimulant effects on behavior
      maintained by a fixed-interval schedule of reinforcement. PAL-313, which has a
      relatively low selectivity for releasing dopamine vs. serotonin, increased
      dopamine levels, but did not induce behavioral-stimulant effects. PAL-287, which
      is relatively nonselective in releasing dopamine and serotonin, did not increase
      dopamine levels or induce behavioral-stimulant effects. These results demonstrate
      that increasing serotonergic activity attenuates dopamine release and dopamine
      mediated behavioral effects of monoamine releasers. In addition, these results
      support further investigation of PAL-313 and similar compounds as a potential
      medication for treating psychostimulant abuse.

PMID- 19766135
TI  - False-negative results by enzyme-linked immunospot assay for interferon-gamma
      among patients with culture-confirmed tuberculosis.

PMID- 19766134
TI  - Sex differences in tolerance to the locomotor depressant effects of lobeline in
      periadolescent rats.
AB  - Lobeline is being tested in clinical trials as a pharmacotherapy for
      methamphetamine abuse and attention deficit hyperactivity disorder. Preclinical
      research demonstrates that lobeline produces locomotor hypoactivity apart from
      its therapeutic effects; however, the hypothesis that there are sex differences
      in hypoactivity or in the development of tolerance to its locomotor depressant
      effects has not been investigated. Periadolescent rats were injected with saline
      to determine baseline locomotor activity. Animals received saline or lobeline
      (1.0-10mg/kg) daily for 7 consecutive days (post natal days 29-35), and were
      challenged with saline 24h later to assess baseline activity. Lobeline produced
      hypoactivity in total horizontal activity and center distance travelled.
      Tolerance developed to the lobeline-induced hypoactivity and sex differences in
      lobeline tolerance were observed on both measures. Females acquired tolerance to
      lobeline 5.6 mg/kg at a slower rate than males. Saline challenge revealed a
      linear dose-dependent trend of hyperactivity on both measures, which indicates
      that rats exhibited altered locomotor behavior 24h after the final lobeline
      treatment. These findings demonstrate sex differences in the hypoactive response
      to lobeline prior to puberty and suggest that females may experience more
      locomotor depressant effects than males. Chronic lobeline may induce
      hyperactivity following cessation of treatment.

PMID- 19766137
TI  - Tuberculous vertebral osteomyelitis: findings of a 10-year review of experience
      in a UK centre.

PMID- 19766138
TI  - Difficulties in the diagnosis and management of a US servicemember presenting
      with possible chronic Q fever.
AB  - A 34 year old corpsman developed acute Q fever upon return from Iraq. Subsequent
      testing demonstrated trace mitral regurgitation and widely discrepant serologic
      testing results between commercial and reference laboratories. We discuss the
      dilemma of isolated minor echocardiographic abnormalities and propose caution in
      the interpretation of Q fever serologic tests.

PMID- 19766136
TI  - Outpatient intravenous treatment for infective endocarditis: safety,
      effectiveness and one-year outcomes.
AB  - OBJECTIVES: To describe the use and outcomes of outpatient antimicrobial therapy
      (OPAT) for infective endocarditis (IE) within the Canterbury region of New
      Zealand over an 8 year period. METHODS: All cases of IE admitted to Christchurch
      Hospital were reviewed. Prospectively collected data from our OPAT service's
      database and retrospective data from case notes were analysed. RESULTS: There
      were 213 episodes of IE meeting modified Duke Criteria over this time. Patients
      received OPAT in 100 episodes. Viridans streptococci were the infecting organism
      in 34, Staphylococcus aureus in 27, and enterococci in 10. Adverse events were
      encountered in 27 episodes. Of these, 24 were related to intravenous lines,
      infusion devices or adverse drug reactions which resolved with change of
      treatment. There were 3 serious adverse events which were likely to have occurred
      in hospital. During 12-month follow-up there were 5 further episodes of IE and 2
      deaths unlikely to be directly related to the episode of IE. CONCLUSIONS: Despite
      significant co-morbidities and complications, nearly half of all patients with
      IE, including those with disease due to S. aureus and enterococci, successfully
      completed their treatment as outpatients. Continuous infusion devices were
      successfully used in 32 patients, including 22 with disease due to S. aureus.

PMID- 19766139
TI  - A 9 year follow up of post herpetic neuralgia and predisposing factors in elderly
      patients following herpes zoster.
AB  - To characterise predisposition to post herpetic neuralgia following herpes
      zoster. DESIGN: Late follow up of patients originally admitted with acute zoster
      to a double blind randomised placebo controlled study of oral acyclovir over 60
      years of age. SETTING: Two UK cities of 1.5 million population. RESULTS: 158 of
      the 298 patients from the original study were available for evaluation at a mean
      follow up of 9 years. Thirty four (21%) described experiencing pain from the
      zoster within the previous 12 months. Pain at follow up was associated with
      characteristics at the time of acute zoster of: moderate or severe acute pain (p
      = 0.006), prodromal pain >72 h before rash (p = 0.006), severity of rash (p =
      0.033) and female gender (p = 0.046). There was no association between pain at 9
      year follow up and use of placebo or aciclovir nor with the presence or absence
      of pain at the point of discharge from the original study. Further analysis of 17
      of the 34 patients with long term pain who have full data available, the median
      pain score was 4 out of 10 and more than 50% described persistent pain and
      interference with sleep. CONCLUSION: Long term pain in the elderly following
      zoster is associated with identifiable characteristics during the acute illness.

PMID- 19766140
TI  - Quantitative monitoring of activity-dependent bulk endocytosis of synaptic
      vesicle membrane by fluorescent dextran imaging.
AB  - Activity-dependent bulk endocytosis (ADBE) is the dominant synaptic vesicle (SV)
      retrieval mode in central nerve terminals during periods of intense neuronal
      activity. Despite this fact there are very few real time assays that report the
      activity of this critical SV retrieval mode. In this paper we report a simple and
      quantitative assay of ADBE using uptake of large flourescent dextrans as fluid
      phase markers. We show that almost all dextran uptake occurs in nerve terminals,
      using co-localisation with the fluorescent probe FM1-43. We also demonstrate that
      accumulated dextran cannot be unloaded by neuronal stimulation, indicating its
      specific loading into bulk endosomes and not SVs. Quantification of dextran
      uptake was achieved by using thresholding analysis to count the number of loaded
      nerve terminals, since monitoring the average fluorescence intensity of these
      nerve terminals did not accurately report the extent of ADBE. Using this analysis
      we showed that dextran uptake occurs very soon after stimulation and that it does
      not persist when stimulation terminates. Thus we have devised a simple and
      quantitative method to monitor ADBE in living neurones, which will be ideal for
      real time screening of small molecule inhibitors of this key SV retrieval mode.

PMID- 19766141
TI  - Extraction of catalytically active neuraminidase of H5N1 influenza virus using
      thrombin proteolytic cleavage.
AB  - The stalk of influenza neuraminidase (NA) has been a target of cleavage by
      various proteases, resulting in the release of catalytically active globular
      heads from virus particles. However, despite successful cases in a number of
      influenza subtypes, this strategy could not be applied to all influenza viruses
      due to high variation of the NA stalk. In the present study, reverse genetics was
      employed to construct non-pathogenic recombinant influenza A viruses, termed
      rgH1N1(LVPR) and rgH1N1(LVPR-GS), that harbor the NA of H5N1 virus engineered to
      contain a specific thrombin cleavage site at the stalk region. By using thrombin
      to cleave NA at its stalk, a productive extraction of NA globular heads could be
      obtained from purified rgH1N1(LVPR). Furthermore, it was found that the NA of
      rgH1N1(LVPR-GS) could be cleaved by endogenous thrombin present in embryonated
      chicken eggs, resulting in the release of NA globular heads into allantoic
      fluids. These data highlight the use of thrombin cleavage as an effective
      strategy for extraction of active NA heads directly from live viral particles not
      only of H5N1 but, theoretically, of any subtype of influenza A viruses.

PMID- 19766142
TI  - Naturally occurring mutations at residues 253 and 284 in VP2 contribute to the
      cell tropism and virulence of very virulent infectious bursal disease virus.
AB  - Infectious bursal disease virus (IBDV) is responsible for the highly contagious
      infectious bursal disease in chickens. Previously, by blind passage, a vvIBDV Gx
      strain was attenuated to the Gt strain, and a strain CEF-9 with intermediate
      characters was obtained during attenuation. Since CEF-9 exhibited only two
      interesting amino acid mutations (Q253H and A284T) on loops P(DE) and P(FG) at
      the tip of VP2 spikes, we hypothesized that, either function separately or in
      combination, they define the cell tropism and virulence of vvIBDV. To test this
      hypothesis, Q253H and A284T were introduced individually or in combination into
      VP2 of the Gx or Gt strain to obtain six modified clones. Using reverse genetics,
      combined mutations of Q253H and A284T could adapt vvIBDV to non-permissive CEF
      cells (rGx-F9VP2) but any single mutation could not. In vivo, rGx-F9VP2 did not
      cause mortality while the Gx strain induced 66.7% mortality. Dual evidence from
      natural and rescued strains identified that the cell tropism of vvIBDV to CEF
      cells was determined by the combined VP2 mutations Q253H and A284T, but not by
      single mutation. The two residues were mainly responsible for the virulence of
      vvIBDV. These findings may be helpful in the design of new tailored IBDV
      vaccines.

PMID- 19766143
TI  - Behavioural and electrophysiological lateralization in a social (Apis mellifera)
      but not in a non-social (Osmia cornuta) species of bee.
AB  - Recent evidence suggests that asymmetry between the left and right sides of the
      brain is not limited to vertebrates but extends to invertebrates as well. We
      compared olfactory lateralization in two species of Hymenoptera Apoidea, the
      honeybee (Apis mellifera), a social species, and the mason bee (Osmia cornuta), a
      solitary species. Recall of the olfactory memory 1 h after training to associate
      an odour with a sugar reward, as revealed by the bee extending its proboscis when
      presented with the trained odour, was better in honeybees trained with their
      right than with their left antenna. No such asymmetry was observed in mason bees.
      Similarly, electroantennographic responses to a floral volatile compound and to
      an alarm pheromone component were higher in the right than in the left antenna in
      honeybees but not in mason bees. These findings seem to support recent game
      theoretical models suggesting that population-level lateralization is more likely
      to have evolved in social than in non-social species.

PMID- 19766144
TI  - Odor detection and odor discrimination in subadult and adult rats for two
      enantiomeric odorants supported by c-fos data.
AB  - The study investigated the olfactory sensitivity and odor discrimination ability
      of male Wistar rats for the two closely related enantiomic odorants carvone and
      limonene. Enantiomers have identical chemical and physical properties but many
      are known to have different odor qualities for humans. Our psychophysical
      experiments revealed that subadult animals (about 2 months old) demonstrated
      higher olfactory sensitivities--lower detection thresholds--for D- and L-limonene
      than the adult conspecifics (about 6 months old). In the discrimination tasks at
      higher odor concentrations all animals were able to discriminate between the D-
      and L-odorant but subadults demonstrated lower discrimination thresholds. Within
      each age group no significant difference could be established. To elucidate
      neural correlates of our behavioral results, we have used c-fos expression to
      provide a global map of neuronal activity, with single cell resolution, in the
      olfactory bulb of D- and L-carvone exposed animals. The two carvone odors elicit
      different patterns of neuronal activity in the olfactory bulb, however, with
      partially overlapping activated areas. Our behavioral and immunhistochemical
      results allow to assume that the D- and L-forms of the two enantiomeric odorants
      have different odor qualities. Our study further demonstrates that the odor
      quality of an odorant depends not only on the atoms of the molecule, its chemical
      structure or on the presence of a functional group. Other parameters like, e.g.
      interaction profiles with different peptides, optical rotation of the polarized
      light--as seen in the enantiomers of an odorant--might also contribute to the
      quality of an odor.

PMID- 19766145
TI  - The aromatase inhibitor 1,4,6-androstatriene-3,17-dione (ATD) reduces
      disinhibitory behavior in intact adult male rats treated with a high dose of
      testosterone.
AB  - Anabolic androgenic steroids and high testosterone doses have been reported to
      induce impulsive behavior in man and behavioral disinhibition in rats. The
      purpose of the present study was to investigate whether aromatization of
      testosterone to estradiol is of importance for the behavioral disinhibiting
      effect of a high testosterone dose in adult male rats. Testosterone administered
      via five testosterone-filled silastic capsules implanted subcutaneously (s.c.) to
      non-castrated, group-housed rats for six days induced behavioral disinhibition in
      a modified Vogel's drinking conflict model and yielded supraphysiological serum
      levels of testosterone and increased accessory sex organ weights. Moreover,
      concurrent administration of the aromatase inhibitor 1,4,6-androstatriene-3,17
      dione (ATD; 60 mg/kg/day s.c.) decreased behavioral disinhibition in testosterone
      treated rats (without affecting accessory sex organ weights) while behavior was
      not significantly affected in sham-treated animals. Since some reports indicate
      that ATD, in addition to inhibit aromatase, also may affect the binding of
      testosterone to the androgen receptor, the effect of the non-steroidal androgen
      receptor antagonist flutamide was investigated. Flutamide treatment did not
      affect disinhibited behavior in testosterone-treated rats. However, in sham
      treated animals, flutamide (50mg/kg/day) produced behavioral disinhibition. These
      results suggest that estradiol is of importance in the mechanisms underlying
      behavioral disinhibition in non-castrated rats treated with a high testosterone
      dose. Speculatively, aromatization may be involved in pro-impulsive effects of
      high testosterone doses in humans.

PMID- 19766146
TI  - Distinct contributions of the hippocampus and medial prefrontal cortex to the
      "what-where-when" components of episodic-like memory in mice.
AB  - There is a current controversy regarding whether non-human animals have a
      capacity for episodic memory, defined by the ability to remember what happened
      and where and when it occurred. It is also unclear which brain structures support
      the "what," "where," and "when" aspects of episodic memory. Here we addressed
      these issues by testing episodic memory in mice, using an object recognition task
      that has previously been employed to assess the "what," "where," and "when"
      components of recognition memory. Whereas intact mice remembered which objects
      they had explored, as well as when and where they were experienced, mice with
      damage to the hippocampus were impaired on all three components of the task. In
      contrast, animals with medial prefrontal cortical lesions were selectively
      impaired on the "where" component of the task, but had intact memory for "what"
      and "when." These results are consistent with the hypothesis that the hippocampus
      integrates the "what," "where," and "when" features of unique experiences,
      whereas the prefrontal cortex makes a more selective contribution to retrieving
      source information about where events occurred.

PMID- 19766147
TI  - Plasmodium falciparum culture: the benefits of shaking.
AB  - Despite evidence that the suspension of malaria cultures leads to improved
      parasite growth, the practice of culturing the parasite under static conditions
      remains widespread. Here, extending previous work, we have quantified the
      favourable effects of continuous agitation on three indices of culture growth:
      (i) parasite yield, (ii) culture synchrony after a synchronisation procedure, and
      (iii) the prevalence of multiple infections. In addition, we show that under
      continuous suspension, the time taken for genetically altered parasites to re
      populate cultures post-transfection is dramatically reduced.

PMID- 19766148
TI  - Expression and cellular localisation of calpain-like proteins in Trypanosoma
      brucei.
AB  - Calpains are a ubiquitous family of calcium-dependent cysteine proteases involved
      in a wide range of cell regulatory and differentiation processes. In many
      protozoan organisms, atypical calpains have been discovered that lack the
      characteristic calcium-binding penta-EF-hand motif of typical vertebrate calpains
      and most of these novel calpain-like proteins are non-enzymatic homologues of
      typical calpains. The gene family is particularly expanded in ciliates and
      kinetoplastids, comprising 25 members in the parasite Trypanosoma brucei. Unique
      to kinetoplastids, some calpain-like proteins contain N-terminal dual
      myristoylation/palmitoylation signals, a protein modification involved in protein
      membrane associations. We analyzed the expression of calpain-like proteins in the
      insect (procyclic) and bloodstream-stage of T. brucei using quantitative real
      time PCR and identified the differential expression of some of the calpain genes.
      We also present a comprehensive analysis of the subcellular localisation of
      selected members of this protein family in trypanosomes. Here, of particular
      interest is the role of protein acylation for targeting to the flagellum. We show
      that, although acylation is important for flagellar targeting, additional signals
      are required to specify the precise subcellular localisation.

PMID- 19766149
TI  - C-terminal processing of GABARAP is not required for trafficking of the
      angiotensin II type 1A receptor.
AB  - OBJECTIVE: GABARAP, a small (117 aa) trafficking protein, binds to the C
      terminal, cytoplasmic domain of rat angiotensin type-1A receptor (AT(1)R), the
      predominant effector of the octapeptide angiotensin II (Ang II) (Cook et al.,
      Circ. Res. 2008;102:1539-47). The objectives of this study were to map the
      interaction domains of GABARAP and AT(1)R, to determine the effect of GABARAP
      association on AT(1)R signaling activity, and to determine the importance of post
      translational processing of GABARAP on accumulation of AT(1)R on the plasma
      membrane and its signaling function. RESULTS: Deletion analysis identified two
      regions within GABARAP necessary for interaction with AT(1)R in yeast two-hybrid
      assays: 1) a domain comprised of residues 32-51 that is nearly identical to that
      involved in binding and intracellular trafficking of the GABA(A) receptor and 2)
      a domain encompassing the C-terminal 21 aa. The GABARAP interaction domain of
      AT(1)R was delimited to the 15 aa immediately downstream of the last membrane
      spanning region. Overexpression of GABARAP in rat adrenal pheochromocytoma PC-12
      cells increased the cell-surface expression of AT(1)R and Ang II-dependent
      activation of the cAMP signaling pathway. Residues within AT(1)R necessary for
      these responses were identified by mutational analysis. In PC-12 cells, GABARAP
      was constitutively and quantitatively cleaved at the C-terminus peptide bond and
      this cleavage was prevented by mutation of Gly(116). Wild-type GABARAP and the
      G116A mutant were, however, equally effective in stimulating AT(1)R surface
      expression and signaling activity. CONCLUSIONS: GABARAP and AT(1)R interact
      through discrete domains and this association regulates the cell-surface
      accumulation and, consequently, ligand-induced function of the receptor. Unlike
      that observed with the GABA(A) receptor, this regulation is not dependent on C
      terminal processing and modification of GABARAP.

PMID- 19766150
TI  - Cortistatin attenuates vascular calcification in rats.
AB  - Cortistatin (CST) is a newly discovered polypeptide with multiple biological
      activities that plays a regulatory role in the nervous, endocrine and immune
      systems. However, the role of CST in the pathogenesis of cardiovascular diseases
      remains unclear. In this study, we investigated in rats whether CST inhibits
      vascular calcification induced by vitamin D3 and nicotine treatment in vivo and
      calcification of cultured rat vascular smooth muscular cells (VSMCs) induced by
      beta-glycerophosphate in vitro and the underlying mechanism. We measured rat
      hemodynamic variables, alkaline phosphatase (ALP) activity, calcium deposition
      and pathological changes in aortic tissues and cultured VSMCs. CST treatment
      significantly improved hemodynamic values and arterial compliance in rats with
      vascular calcification, by decreasing systolic blood pressure, pulse pressure,
      left ventricular end-systolic pressure and left ventricular end-diastolic
      pressure. CST also significantly decreased ALP activity and calcium deposition,
      alleviated pathological injury and down-regulated the mRNA expression of type III
      sodium-dependent phosphate co-transporter-1 (Pit-1) in aortic tissues. It dose
      independently inhibited the calcification of VSMCs by decreasing ALP activity and
      calcium deposition, alleviating pathologic injury and down-regulating Pit-1 mRNA
      expression. As with CST treatment, ALP activation and calcium deposition were
      decreased significantly on treatment with ghrelin, the endogenous agonist of
      growth hormone secretagogue receptor 1a (GHSR1a), but not significantly with
      somatostatin-14 or proadrenomedullin N-terminal 20 peptide in VSMCs. Further,
      growth hormone-releasing peptide-6[D-lys], the endogenous antagonist of GHSR1a,
      markedly reversed the increased ALP activity and calcium deposition in VSMCs. CST
      could be a new target molecule for the prevention and therapy of vascular
      calcification, whose effects are mediated by GHSR1a rather than SSTRs or Mrg X2.

PMID- 19766151
TI  - Increased angiotensin II AT1 receptor mRNA and binding in spleen and lung of AT2
      receptor gene disrupted mice.
AB  - To clarify the relationship between Angiotensin II AT(1) and AT(2) receptors, we
      studied AT(1) receptor mRNA and binding expression in tissues from AT(2) receptor
      gene disrupted (AT(2)(-/-)) female mice, where AT(2) receptors are not expressed
      in vivo, using in situ hybridization and quantitative autoradiography. Wild type
      mice expressed AT(1A) receptor mRNA and AT(1) receptor binding in lung
      parenchyma, the spleen, predominantly in the red pulp, and in liver parenchyma.
      In wild type mice, lung AT(2) receptors were expressed in lung bronchial
      epithelium and smooth muscle, and were not present in the lung parenchyma, the
      spleen or the liver. This indicates that AT(1) and AT(2) receptors were not
      expressed in the same cells. In AT(2)(-/-) mice, we found higher AT(1A) receptor
      mRNA and AT(1) receptor binding in lung parenchyma and in the red pulp of the
      spleen, but not in the liver, when compared to littermate wild type controls. Our
      results suggest that impaired AT(2) receptor function upregulates AT(1) receptor
      transcription and expression in a tissue-specific manner and in cells not
      expressing AT(2) receptors. AT(1) upregulation explains the increased sensitivity
      to Angiotensin II characteristic of the AT(2)(-/-) phenotype, consistent with
      enhanced AT(1) receptor activation in a number of tissues.

PMID- 19766152
TI  - Roles of serotonin 5-HT3 receptor in the formation of dendrites and axons in the
      rat cerebral cortex: an in vitro study.
AB  - The serotonin type 3 (5-HT(3)) receptor is an only ligand-gated ion channel among
      14 serotonin receptors. Here, we examined the roles of the 5-HT(3) receptor in
      the formation of dendrites and axons, using a dissociation culture of embryonic
      rat cerebral cortex. Cortical neurons at embryonic day 16 were cultured for 4
      days in the presence of a selective 5-HT(3) receptor agonist with or without an
      antagonist. Neurons were then immunostained by antibodies against microtubule
      associated protein 2 (MAP2) and glutamic acid decarboxylase (GAD) 65. All cells
      expressed MAP2, whereas only limited number of cells expressed GAD65. From the
      immunoreactivity and the cell shape, we tentatively divided neurons into 3 types;
      GAD-positive multipolar, GAD-positive bipolar/tripolar and GAD-negative neurons.
      The total length of axons and dendrites, the number of primary dendrites and the
      dendritic branching of GAD-negative neurons were decreased by the agonist (10 or
      100nM), most of which were reversed by the concomitant treatment of the
      antagonist. In contrast, no or little effect was observed on the formation of
      dendrites and axons of GAD-positive multipolar neurons, and the neurite formation
      of GAD-positive bipolar/tripolar neurons. The present study revealed differential
      roles of the 5-HT(3) receptor in the formation of dendrites and axons of subtypes
      of cortical neurons.

PMID- 19766153
TI  - HIV-1 derived peptides fused to HBsAg affect its immunogenicity.
AB  - The hepatitis B virus (HBV) surface small antigen (HBsAg) self-assembles into
      virus-like particles (VLPs). HBsAg-based VLPs constitute a powerful vector for
      heterologous immunogenic peptides to develop a safe vaccine delivery system. HBV
      and the human immunodeficiency virus type 1 (HIV-1) are frequently associated in
      infection. An HIV-1 class I polyepitope was designed for an HIV-1/HBV vaccine
      prototype based on HBsAg VLPs. Invariable peptides from the original HIV-1
      polyepitope were here permutated to study the influence of epitope order on HIV
      1/HBV VLP immunogenicity. Anti-HIV-1 cellular responses were statistically
      comparable among polyepitope variants. Nevertheless, delivered HIV-1 polyepitopes
      impacted anti-HBsAg carrier immunogenicity in a polyepitope-specific manner. For
      a given set of epitopes, the choice of epitope order in polyepitopes is strategic
      to control immune responses towards HBsAg VLPs used as carrier of foreign
      immunogenic peptides.

PMID- 19766154
TI  - Determinants of food expenditure patterns among older consumers. The Spanish
      case.
AB  - The continuously evolving lifestyles of European consumers are most noticeable in
      the elderly age segment, which, as a result, is drawing increasing attention from
      agrifood companies. The aim of this study is to perform an empirical analysis of
      the main determinants of food expenditure among elderly Spanish consumers, by
      comparing key variables reported in the literature, based on data from different
      years. The performed estimations yield a linear model with three statistically
      significant variables; type of household, level of education--a proxy measure for
      family income--and consumer's age. The results enable us to conclude that
      agrifood companies will need to deal with a changing demographic environment, and
      increase the flexibility of their supply to adjust to the new situation.

PMID- 19766155
TI  - Piccolo knockdown-induced impairments of spatial learning and long-term
      potentiation in the hippocampal CA1 region.
AB  - Neurotransmitter release is regulated at a specific site in nerve terminals
      called the "active zone", which is composed of various cytomatrix proteins such
      as Piccolo (also known as Aczonin) and Bassoon. These proteins share regions of
      high sequence similarity and have very high molecular weights (>400 kDa). Since
      Piccolo knockout mice have not yet been established, the role of Piccolo in the
      neuronal system remains unclear. In this study, we investigated the effects of
      Piccolo antisense oligonucleotide injected into the ventricle on hippocampal long
      term potentiation (LTP) and learning and memory assessed with the novel object
      recognition test and the Morris water maze test. There was no significant
      difference in cognitive memory between Piccolo antisense-treated and vehicle- or
      sense-treated mice; however, spatial learning in Piccolo antisense-treated mice
      was impaired but not in sense- or vehicle-treated mice. Next, we investigated LTP
      formation in these groups in area CA1 and dentate gyrus of the same hippocampal
      slices. The magnitude of LTP in Piccolo antisense-treated mice was significantly
      lower than in sense- or vehicle-treated mice, with no change in basal level.
      Moreover, the level of high K(+)-induced glutamate release in the antisense
      treated mice was significantly lower than in sense-treated mice. Taken together,
      these results indicate that Piccolo plays a pivotal role in synaptic plasticity
      in area CA1 and in hippocampus-dependent learning in mice, and that the
      extracellular levels of glutamate in the hippocampus under stimulated conditions
      are controlled by Piccolo.

PMID- 19766156
TI  - Substance-tailored testing strategies in toxicology: an in silico methodology
      based on QSAR modeling of toxicological thresholds and Monte Carlo simulations of
      toxicological testing.
AB  - The design of toxicological testing strategies aimed at identifying the toxic
      effects of chemicals without (or with a minimal) recourse to animal
      experimentation is an important issue for toxicological regulations and for
      industrial decision-making. This article describes an original approach which
      enables the design of substance-tailored testing strategies with a specified
      performance in terms of false-positive and false-negative rates. The outcome of
      toxicological testing is simulated in a different way than previously published
      articles on the topic. Indeed, toxicological outcomes are simulated not only as a
      function of the performance of toxicological tests but also as a function of the
      physico-chemical properties of chemicals. The required inputs for our approach
      are QSAR predictions for the LOAELs of the toxicological effect of interest and
      statistical distributions describing the relationship existing between in vivo
      LOAEL values and results from in vitro tests. Our methodology is able to
      correctly predict the performance of testing strategies designed to analyze the
      teratogenic effects of two chemicals: di(2-ethylhexyl)phthalate and Indomethacin.
      The proposed decision-support methodology can be adapted to any toxicological
      context as long as a statistical comparison between in vitro and in vivo results
      is possible and QSAR models for the toxicological effect of interest can be
      developed.

PMID- 19766157
TI  - A 13-week dietary toxicity study in rats of a Napin-Rich Canola Protein Isolate.
AB  - The objective was to study the safety of a Napin-Rich Canola Protein Isolate
      (NRCPI) fed to rats at various levels for 13-weeks. The study included four
      groups (20 animals/sex/group) of young Sprague Dawley rats. They were fed ad
      libitum with an AIN-93G based protein-free diet containing, respectively, 5%, 10%
      and 20% (w/w) NRCPI (test article) or 20% (w/w) vitamin-free casein (control
      article). Protein levels were adjusted at 18% in all groups with vitamin-free
      casein. Body weights, food consumption, locomotor activity and behavioral and
      clinical pathology parameters were recorded at various points in the study,
      followed by macroscopic examination, determination of organ weights and
      microscopic examination at termination. There were no test article-related
      effects on ophthalmology, functional observations, hematology, serum chemistry,
      urinalysis, organ weights and macroscopic or microscopic findings. Lower body
      weight gains were observed in the 10% NRCPI-treated males and the 20% NRCPI
      treated males and females. The lower body weight gains were associated with
      significantly lower food consumption. Therefore, for NRCPI the No Observed
      Adversed Effect Level (NOAEL) was considered to be 20% (the highest fed level);
      equivalent to 12.46 g/kg BW/day for males and 14.95 g/kg BW/day for females. The
      NRCPI was considered safe under the tested conditions.

PMID- 19766158
TI  - Genetic polymorphisms in the dopamine-2 receptor (DRD2), dopamine-3 receptor
      (DRD3), and dopamine transporter (SLC6A3) genes in schizophrenia: Data from an
      association study.
AB  - OBJECTIVE: To investigate the association between dopaminergic polymorphisms
      [DRD2 -141C Ins/Del, DRD3 Ser9Gly, and SLC6A3 VNTR] and schizophrenia. METHODS:
      Two hundred and eighty-eight outpatients with schizophrenia (DSM-IV criteria)
      [mean age (SD)=36.4 (12.4), 60.1% males] and 421 unrelated healthy controls [mean
      age (SD)=40.6 (11.3), 51.3% males] from a homogeneous Spanish Caucasian
      population were genotyped using standard methods. RESULTS: There was a
      significant difference in genotype distribution for the DRD2 -141C Ins/Del
      polymorphism [(chi(2) (2)=12.35, corrected p=0.012]. The -141C Del allele was
      more common in patients than in controls [0.19 vs. 0.13; chi(2) (1)=9.14,
      corrected p=0.018, OR (95% CI)=1.57 (1.17-2.10)]. Genotype and allele
      distributions for DRD3 Ser9Gly and SLC6A3 VNTR polymorphisms were similar in both
      groups. However, there was tentative evidence of an interaction effect between
      DRD3 Ser9Gly and SLC6A3 VNTR [Wald=9.56 (4), p=0.049]. Compared to the SLC6A3
      10/10 genotype category, the risk of schizophrenia was halved among those with
      9/10 [OR=0.51 (95% CI=0.30-0.89), p=0.017]. This protective effect was only
      present in combination with DRD3 Ser/Ser genotype because of the significant
      interaction between 9/10 and both Ser/Gly [OR=2.45 (95% CI=1.16-5.17), p=0.019]
      and Gly/Gly [OR=3.80 (95% CI=1.24-11.63), p=0.019]. CONCLUSIONS: This study
      provides evidence that a genetic variant in the DRD2 gene and possible
      interaction between DRD3 and SLC6A3 genes are associated with schizophrenia.
      These findings warrant examination in replication studies.

PMID- 19766159
TI  - Amisulpride-induced mania with interictal psychosis.

PMID- 19766160
TI  - Studies on anti-inflammatory, antipyretic and analgesic properties of Caesalpinia
      bonducella F. seed oil in experimental animal models.
AB  - Caesalpinia bonducella FLEMING (Caesalpiniaceae) plant is well known for its
      medicinal and therapeutic values in Indian Ayurveda. However, to be clinically
      useful, more scientific data are needed. Therefore, in the present study, we
      investigated the effects of C. bonducella seed oil on acute and chronic
      inflammation. To assess the anti-inflammatory, antipyretic and analgesic
      activities, varied concentrations of the seed oil of C. bonducella (100, 200 and
      400mg/kg orally) were tested in carrageenan-induced rat paw oedema, brewer's
      yeast-induced pyrexia, acetic acid-induced writhing and hot plate reaction time
      in experimental rats. The paw volumes, pyrexia and writhes in experimental rats
      were reduced significantly (p<0.05) as compared to that of control, and hot plate
      test showed significant licking effect in rats. These results clearly indicate
      that the oil of C. bonducella seeds could be a potential source for using as anti
      inflammatory, antipyretic and analgesic agent.

PMID- 19766161
TI  - Antioxidant and antibacterial activities of the leaf essential oils of Himalayan
      Lauraceae species.
AB  - The leaf essential oils from seven Himalayan Lauraceae species viz. Neolitsea
      pallens, Lindera pulcherrima, Dodecadenia grandiflora, Persea duthiei, Persea
      odoratissima, Persea gamblei and Phoebe lanceolata exhibited potent antioxidant
      and antibacterial activities. The in vitro antioxidant activity was assessed by
      using beta-carotene bleaching assay, reducing power, DPPH radical scavenging and
      inhibition of lipid peroxidation methods. The oils of D. grandiflora and L.
      pulcherrima showed a potent free radical scavenging activity as evidenced by low
      IC(50) value for DPPH radical (0.032 mg/ml and 0.087 mg/ml, respectively) and
      inhibition of lipid peroxidation (in between IC(50)=0.44 mg/ml and IC(50)=0.74
      mg/ml, respectively). The oils were tested against three Gram negative
      (Escherichia coli, Salmonella enterica enterica and Pasturella multocida) and one
      Gram positive (Staphylococcus aureus) bacteria at different concentrations using
      disc diffusion and tube dilution methods. The inhibition zones (IZ) and MIC
      values for bacterial strains were in the range of 8.7-22.0mm and 3.90-31.25
      microl/ml, respectively.

PMID- 19766162
TI  - Serum levels of carbonylated and nitrosylated proteins in mobbing victims with
      workplace adjustment disorders.
AB  - AIM: Today the most important problem in the work place is psychological abuse,
      which may affect the health because of high levels of stress and anxiety. There
      is evidence that most psychiatric disorders are associated with increased
      oxidative stress but nothing is reported about the presence of oxidative stress
      in mobbing victims. METHODS: This study has been carried out in a group of 19
      patients affected by workplace mobbing-due adjustment disorders, in comparison
      with 38 healthy subjects, to evaluate whether oxidative stress may be induced by
      mobbing. RESULTS: Serum levels of protein carbonyl groups and of nitrosylated
      proteins, biological markers of oxidative stress conditions, were higher than
      those measured in healthy subjects. CONCLUSIONS: These findings may contribute to
      a better understanding of the redox homeostasis dysregulation occurring in
      victims of workplace mobbing.

PMID- 19766163
TI  - Testicular cell adhesion molecule 1 (TCAM1) is not essential for fertility.
AB  - Testicular cell adhesion molecule 1 (Tcam1) is a testis-expressed gene that is
      evolutionarily conserved in most mammalian species. The putative location of
      TCAM1 on the cell surface makes it an attractive contraceptive target to study.
      We found that Tcam1 transcription is enriched in the adult testis, and in situ
      hybridization revealed that Tcam1 is expressed in pachytene to secondary
      spermatocytes. Immunofluorescence for TCAM1 protein showed strong expression
      along cell membranes of spermatocytes and weak localization to round spermatids.
      In light of this evidence, we hypothesized that TCAM1 interacts with an unknown
      receptor on the surface of Sertoli cells and that this interaction is important
      for germ cell-Sertoli cell interactions. However, Tcam1 knockout mice that we
      generated are fertile, and testis weights and sperm counts were not significantly
      altered. Therefore, we conclude that TCAM1 is not essential for male fertility or
      germ cell function in Mus musculus.

PMID- 19766164
TI  - Propensity and sensitivity measures of fear and disgust are differentially
      related to emotion-specific brain activation.
AB  - Neuroimaging studies on individual differences in experiencing disgust and fear
      have indicated that disgust propensity and trait anxiety are able to moderate
      brain activity. The moderating role of disgust sensitivity and anxiety
      sensitivity has not been investigated thus far. Both sensitivity traits refer to
      the tendency of a person to perceive harmful consequences of experiencing fear
      and disgust. Eighteen female subjects viewed and subsequently rated pictures for
      the elicitation of disgust, fear and a neutral affective state. The viewing of
      the aversive pictures was associated with activation of visual processing areas,
      the amygdala, the insula and the orbitofrontal cortex (OFC). In the disgust
      condition, disgust propensity was positively correlated with activation of
      attention-related areas (parietal cortex, anterior cingulate cortex (ACC)) and
      brain regions involved in valence and arousal processing (OFC, insula). For the
      fear condition, we observed positive correlations between trait anxiety and
      activation of the ACC, the insula, and the OFC. Correlations between brain
      activity and sensitivity measures were exclusively negative and concerned areas
      crucial for emotion regulation, such as the medial and dorsolateral prefrontal
      cortex (MPFC, DLPFC). Thus, individuals high in disgust/anxiety sensitivity might
      have difficulties to successfully control the specific affective experience.

PMID- 19766165
TI  - Palisade endings are present in canine extraocular muscles and have a cholinergic
      phenotype.
AB  - Classical proprioceptors, like Golgi tendon organs and muscle spindles are absent
      in the extraocular muscles (EOMs) of most mammals. Instead, a nerve end organ was
      detected in the EOMs of each species including sheep, cat, rabbit, rat, monkey,
      and human examined so far: the palisade ending. Until now no clear evidence
      appeared that palisade endings are also present in canine EOMs. Here, we analyzed
      dog EOMs by confocal laser scanning microscopy, 3D reconstruction, and
      transmission electron microscopy. In EOM wholemount preparations stained with
      antibodies against neurofilament and synaptophysin we could demonstrate typical
      palisade endings. Nerve fibers coming from the muscle extend into the tendon.
      There, the nerve fibers turn 180 degrees and return to branch into preterminal
      axons which establish nerve terminals around a single muscle fiber tip. Fine
      structural analysis revealed that each palisade ending in dog EOMs establish
      nerve terminals on the tendon. In some palisade endings we found nerve terminals
      contacting the muscle fiber as well. Such neuromuscular contacts have a basal
      lamina in the synaptic cleft. By using an antibody against choline
      acetyltransferase (ChAT) we proved that canine palisade endings are ChAT
      immunoreactive. This study shows that palisade endings are present in canine
      EOMs. In line with prior findings in cat and monkey, palisade endings in dog have
      a cholinergic phenotype.

PMID- 19766166
TI  - TAAR 6 and HSP-70 variations associated with bipolar disorder.
AB  - We report on the impact of a set of variations located in the HSP-70 (heat shock
      protein 70) and TAAR6 (trace amine associated receptors 6 gene) in a sample of
      bipolar patients. Holding a diagnosis of BPD was the first outcome measure.
      Response to pharmacotreatment in bipolar patients was the secondary outcome
      measure. One hundred seventy-one bipolar patients and 288 controls were enrolled
      for the study. Patients were administered HAM-D, YMRS and CGI at baseline and
      discharge by independent psychiatrists blind to genotypes. As a result,
      homozygosis at rs2075799 (HSP-70) was found to be more represented in controls
      than in cases (p=0.000009). The investigated variations did not show impact on
      treatment outcome. This study provides preliminary evidence that HSP-70 may play
      a role in the disrupted mechanisms that lead to BPD. Further confirmatory
      analyses in this direction are mandatory.

PMID- 19766167
TI  - Antibody binding to cell surface amyloid precursor protein induces neuronal
      injury by deregulating the phosphorylation of focal adhesion signaling related
      proteins.
AB  - The biological function of full-length amyloid-beta protein precursor (APP), the
      precursor of Abeta, is not fully understood. Mounting studies reported that
      antibody binding to cell surface APP causes neuronal injury. However, the
      mechanism of cell surface APP mediating neuronal injury remains to be determined.
      Colocalization of APP with integrin on cell surface leads us to suppose that
      focal adhesion (FA) related mechanism is involved in surface APP-mediated
      neuronal injury. In the present study, results demonstrated that primary cultured
      neurons treated with antibody against APP-N-terminal not only caused neuronal
      injury and aberrant morphologic changes of neurite, but also induced reaction of
      FA proteins appearing an acute increase then decrease pattern. Moreover, the
      elevation of tyrosine phosphorylation of FA proteins including paxillin and focal
      adhesion kinase (FAK), and down-regulated expression of protein tyrosine
      phosphatase (PTP1B) induced by APP antibody were prevented by inhibitor of Src
      protein kinases 4-amino-5-(4-chlorophenyl)-7(t-butyl) pyrazol (3,4-D) pyramide
      (PP2) and G protein inhibitor pertussis toxin (PTX), implying that Src family
      kinase and G protein play roles in APP-induced FA signals. In addition,
      pretreatment with PTX and PP2 was able to suppress APP-antibody induced neuronal
      injury. Taken together, the results suggest a novel mechanism for APP mediating
      neuronal injury through deregulating FA signals.

PMID- 19766168
TI  - Differential effects of eyes open or closed in darkness on brain activation
      patterns in blind subjects.
AB  - In functional brain imaging, specific task conditions can be compared to a
      reference condition which is often eyes-open or eyes-closed in darkness without
      the execution of a specific task. Previous fMRI studies in sighted subjects have
      shown that eyes-open in darkness, without visual stimulation, increases the
      relative activity in cortical ocular motor and attentional areas ("exteroceptive"
      state; contrast OPEN>CLOSED). By contrast, eyes-closed causes a relative signal
      increase in sensory systems ("interoceptive" state; contrast CLOSED>OPEN). In the
      present study we used fMRI to determine whether these differential brain activity
      states can also be found in congenitally blind subjects: there were intragroup
      differences between the OPEN and CLOSED conditions. These differences were,
      however, less pronounced and occurred in other areas than in sighted controls.
      The contrast OPEN>CLOSED revealed a relative signal increase in the left frontal
      eye field, the middle occipital gyrus bilaterally and in the anterior cingulum.
      Relative signal increases in occipital cortex areas and the anterior cingulum
      were also apparent for this contrast in the intergroup comparison (congenitally
      totally blind subjects vs. sighted controls). They reflect the increased
      attentional load or arousal during the eyes-open condition and could be
      indicative of a functional reorganization of the occipital cortex in the blind.
      The contrast CLOSED>OPEN in the congenitally totally blind subjects lead to
      relative activations in the somatosensory cortex bilaterally, the middle temporal
      gyrus on the left and the frontal gyri on the right. These activations are
      residues of the "interoceptive" state found in sighted controls.

PMID- 19766169
TI  - Neuroprotection against staurosporine by metalloporphyrins independent of
      antioxidant capability.
AB  - Metalloporphyrin catalytic antioxidants are remarkably useful in protecting cells
      and tissues in a wide array of disease models, attributed primarily to
      functioning as superoxide dismutase (SOD) mimetics or by scavenging other
      reactive oxygen species (ROS). However, we recently showed that neuroprotection
      against Ca(2+)-dependent excitotoxic insults did not correlate with antioxidant
      strength or capability [25], raising the question of whether scavenging of ROS
      underlies neuroprotection in other types of neuronal injury. The protein kinase
      inhibitor staurosporine causes neuronal demise primarily by apoptosis.
      Neuroprotection from staurosporine by a limited number of metalloporphyrin
      antioxidants has previously been attributed to antioxidant action. In the current
      study, a wide array of anionic and cationic metalloporphyrins and porphyrins,
      ranging in antioxidant strength or capability, provided protection against
      staurosporine in cortical neuron and cerebellar granule neuron (CGN) culture.
      Neuroprotection did not correlate with antioxidant strength or capability. In CGN
      but not cortical neuron cultures, NMDA receptor antagonists also prevented
      neurotoxicity, so metalloporphyrins may also target this secondary mode of death
      induced by staurosporine. Neuroprotection observed with antioxidant-inactive
      controls raises the possibility of an additional, or perhaps alternative,
      mechanism by antioxidant analogs not involving ROS scavenging.

PMID- 19766170
TI  - DJ-1 mRNA anatomical localization and cell type identification in the mouse
      brain.
AB  - Mutations in DJ-1 cause familial Parkinson's disease (PD). The expression pattern
      of DJ-1 in the brain remains controversial. In the present study, we used DJ-1
      deficient mice as negative controls and examined DJ-1 mRNA expression in mouse
      brains. In sequential double labeling on the same sections, in situ hybridization
      of DJ-1 mRNA was followed by immunofluorescence detection of cell type markers.
      We found that DJ-1 mRNA was expressed in the majority of neurons in all brain
      areas examined. In particular, all dopamine neurons in the ventral midbrain
      expressed DJ-1 mRNA. In contrast, the choroid plexus and ependymal cells lining
      the ventricles were the only non-neuronal regions strongly expressing DJ-1 mRNA.
      DJ-1 mRNA was not detected in astrocytes. The fact that DJ-1 mRNA is expressed in
      all nigra dopamine neurons but not in astrocytes suggests that its potential
      neuroprotective role could be cell-autonomous. Moreover, that DJ-1 expression is
      not restricted to substantia nigra dopamine neurons suggests that PD-linked
      mutant DJ-1 may interact with other predisposing factors to cause the relatively
      selective dopamine neuron degeneration in Parkinson's disease.

PMID- 19766171
TI  - Interleukin-1 attenuates normal tension glaucoma-like retinal degeneration in
      EAAC1-deficient mice.
AB  - Glaucoma, one of the leading causes of irreversible blindness, is characterized
      by progressive degeneration of retinal ganglion cells (RGCs) and optic nerves.
      Although glaucoma is often associated with elevated intraocular pressure, recent
      studies have shown a relatively high prevalence of normal tension glaucoma (NTG)
      in glaucoma patient populations. In the mammalian retina, glutamate/aspartate
      transporter (GLAST) is localized to Muller glial cells, whereas excitatory amino
      acid carrier 1 (EAAC1) is expressed in neural cells, including RGCs. Since the
      loss of GLAST or EAAC1 leads to retinal degeneration similar to that seen in NTG,
      we examined the effects of interleukin-1 (IL-1) on RGC death in GLAST- and EAAC1
      deficient mice. IL-1 promoted increased glutamate uptake in Muller cells by
      suppressing intracellular Na(+) accumulation, which is necessary to counteract
      Na(+)-glutamate cotransport. The observed trends for the glutamate uptake
      increase in the wild-type (WT), GLAST- and EAAC1-deficient mice were similar;
      however, the baseline glutamate uptake and intracellular Na(+) concentration in
      the GLAST-deficient mice were significantly lower than those in the wild-type
      mice. Consistently, pretreatment with IL-1 exhibited no beneficial effects on
      glutamate-induced RGC degeneration in the GLAST-deficient mice. In contrast, IL-1
      significantly increased glutamate uptake by Muller cells and the number of
      surviving RGCs in the wild-type and EAAC1-deficient mice. Our findings suggest
      that the use of IL-1 for enhancing the function of glutamate transporters may be
      useful for neuroprotection in retinal degenerative disorders including NTG.

PMID- 19766172
TI  - Crossmodal effects of Guqin and piano music on selective attention: an event
      related potential study.
AB  - To compare the effects of music from different cultural environments (Guqin:
      Chinese music; piano: Western music) on crossmodal selective attention,
      behavioral and event-related potential (ERP) data in a standard two-stimulus
      visual oddball task were recorded from Chinese subjects in three conditions:
      silence, Guqin music or piano music background. Visual task data were then
      compared with auditory task data collected previously. In contrast with the
      results of the auditory task, the early (N1) and late (P300) stages exhibited no
      differences between Guqin and piano backgrounds during the visual task. Taking
      our previous study and this study together, we can conclude that: although the
      cultural-familiar music influenced selective attention both in the early and late
      stages, these effects appeared only within a sensory modality (auditory) but not
      in cross-sensory modalities (visual). Thus, the musical cultural factor is more
      obvious in intramodal than in crossmodal selective attention.

PMID- 19766173
TI  - Fluorescent labeling of both GABAergic and glycinergic neurons in vesicular GABA
      transporter (VGAT)-venus transgenic mouse.
AB  - Inhibitory neurons play important roles in a number of brain functions. They are
      composed of GABAergic neurons and glycinergic neurons, and vesicular GABA
      transporter (VGAT) is specifically expressed in these neurons. Since the
      inhibitory neurons are scattered around in the CNS, it is difficult to identify
      these cells in living brain preparations. The glutamate decarboxylase (GAD) 67
      GFP knock-in mouse has been widely used for the identification of GABAergic
      neurons, but their GAD67 expression was decreased compared to the wild-type mice.
      To overcome such a problem and to highlight the function and morphology of
      inhibitory neurons, we generated four lines of VGAT-Venus transgenic mice (lines
      #04, #29, #39 and #49) expressing Venus fluorescent protein under the control of
      mouse VGAT promoter. We found higher expression level of Venus transcripts and
      proteins as well as brighter fluorescent signal in line #39 mouse brains,
      compared to brains of other lines examined. By Western blots and
      spectrofluorometric measurements of forebrain, the line #39 mouse showed stronger
      GFP immunoreactivity and brighter fluorescent intensity than the GAD67-GFP knock
      in mouse. In addition, Venus was present not only in somata, but also in neurites
      in the line #39 mouse by histological studies. In situ hybridization analysis
      showed that the expression pattern of Venus in the line #39 mouse was similar to
      that of endogenous VGAT. Double immunostaining analysis in line #39 mouse showed
      that Venus-expressing cells are primarily immunoreactive for GABA in cerebral
      cortex, hippocampus and cerebellar cortex and for GABA or glycine in dorsal
      cochlear nucleus. These results demonstrate that the VGAT-Venus line #39 mouse
      should be useful for studies on function and morphology of inhibitory neurons in
      the CNS.

PMID- 19766174
TI  - Ethnic variation in genotype frequencies of delta-aminolevulinic acid dehydratase
      (ALAD).
AB  - Delta-aminolevulinic acid dehydratase (ALAD) is a cytosolic enzyme in the heme
      biosynthetic pathway. The ALAD is controlled by two codominant alleles (ALAD1 and
      ALAD2), which result in a Asn-Lys substitution at amino acid position 59 of the
      mature enzyme based on a single nucleotide polymorphism (SNP) (G177C) leading
      three phenotypes (ALAD1-1, ALAD1-2, and ALAD2-2). Previous studies have shown
      that this polymorphism is related to lead toxicity. There is little evidence
      showing interethnic differences in the distribution of this polymorphism. We
      examined the distribution of genetic variants of the ALAD G177C polymorphism in
      four Asians, three Africans, and three Mexicans. Genomic DNA was extracted from
      blood or bloodstain, and the genotypes for the ALAD polymorphism were determined
      by PCR followed by RFLP digestion and gel electrophoresis. We found a notable
      interethnic disparity in the distribution of ALAD G177C genotypes and alleles.
      The frequencies of ALAD2 in Asian populations were comparable to those in
      Caucasians, while Africans had no mutation allele. These findings may help us
      understand the interethnic disparities in susceptibility to lead toxicity.

PMID- 19766175
TI  - Mice are prone to kidney pathology after prolonged ketamine addiction.
AB  - ICR mice were injected with ketamine for 1, 3 and 6 months and the kidneys and
      urinary bladders were excised and processed for histology. Starting from 1 month,
      all addicted mice showed invasion of mononuclear white cells, either surrounding
      the glomerulus or the other tubules in the kidney. The aggregation of these cells
      extended all the way to the pelvis and ureter. As well, in the urinary bladder,
      the epithelium became thin and there was submucosal infiltration of mononuclear
      inflammatory cells. Silver staining revealed a loss of nerve fibers amongst the
      muscles of the urinary bladder of the treated. Immunohistochemistry on choline
      acetyltransferase which is a marker for cholinergic neurons also demonstrated a
      decrease of those cells. We hypothesized that prolonged ketamine addiction
      resulted in the animals prone to urinary infection.

PMID- 19766176
TI  - The protective effect of alpha-tocopherol against dichromate-induced renal tight
      junction damage is mediated via ERK1/2.
AB  - Renal tight junctions (TJ) play a central role in modulating the paracellular
      pathway. We examined the function, quantity and distribution of TJ proteins:
      occludin and claudin-2 (cln-2), on proximal tubule in a model of acute renal
      failure (ARF) associated with oxidative damage. Since ERK1/2-p modulates TJ
      integrity, we studied their participation in dichromate (Cr(6+)) toxicity. We
      evaluated whether co-administration of the antioxidant alpha-tocopherol (alpha
      TOC) prevents Cr(6+) toxicity in TJ. Female Wistar rats received potassium
      dichromate 15 mg/kg, s.c. (5.3 mg/kg of Cr(6+)) single dose, with or without
      alpha-TOC (125 mg/kg, p.o., daily). Two and 7 days after Cr(6+) treatment,
      oxidative damage was assessed by renal lipid peroxidation (LPO), proximal
      function was estimated by sodium and glucose fractional excretions. Occludin, cln
      2, and ERK1/2-p were detected by immunofluorescence and Western blot. ARF induced
      by Cr(6+) provoked augment in the sodium and glucose urinary looses, increases in
      occludin quantity (6.6- and 15-fold on days 2 and 7, respectively) and the
      mislocation of cln-2. Electrophoresis migration showed a higher molecular weight
      band only in the Cr(6+)-administered groups, suggesting occludin
      hyperphosphorylation. Alpha-TOC treatment diminished the LPO, improved tubular
      function, and preserved TJ location and expression. In summary, we show
      disruption of occludin and cln-2 in ARF induced by Cr(6+)-intoxication. This
      study provides evidence of the beneficial effect of alpha-TOC on TJ structure and
      function undergoing oxidative damage, and we suggest the participation of ERK1/2
      in the mechanisms leading to protection by the antioxidant.

PMID- 19766177
TI  - CYP1A1 and CYP3A4 modulation by dietary flavonoids in human intestinal Caco-2
      cells.
AB  - Flavonoids have been proposed to exert beneficial effects in a multitude of
      disease states. However, evidence of potential toxic actions has also emerged.
      Since large doses of flavonoids can be encountered in the intestine
      simultaneously with ingested drugs and pollutants, this study aimed at
      investigating nine individual flavonoid compounds and their interactions with the
      major intestinal isoforms of cytochrome P450, i.e. CYPs 1A1 and 3A4, using human
      intestinal Caco-2 cells cultivated in a serum-free medium. Genistein, quercetin
      and chrysin provoked a dose-dependent inducing effect on the CYP1A1 activity,
      measured with the EROD assay. However, they did not affect the CYP1A1 mRNA
      expression, suggesting they are not aryl hydrocarbon receptor-ligands in
      intestinal cells and act at a post-transcriptional level. Chrysin, at 50 microM,
      was detected as a potent inhibitor of the TCDD-induced CYP1A1 activity, leading
      the activity to ca. 10% of the TCDD-control value (n=3), this effect involving,
      at least partly, direct interactions at the enzyme level. Quercetin was also
      shown to significantly inhibit the constitutive CYP3A4 activity, measured by the
      6beta-(OH)-testosterone assay, and to impair its induction by 1,25-vitamin D(3).
      Chrysin, quercetin and genistein, were detected as significant inhibitors of the
      1,25-vitamin D(3)-induced CYP3A4 activity. In vivo, these effects could result in
      reduced activation of procarcinogens and/or in drug bioavailability limitation.
      They underline the importance of intestinal studies to assess food safety and
      health risks linked to the ingestion of flavonoid-enriched supplements or
      functional foods.

PMID- 19766178
TI  - The influence of polymer architecture on the protective effect of novel comb
      shaped amphiphilic poly(allylamine) against in vitro enzymatic degradation of
      insulin--towards oral insulin delivery.
AB  - Nanocomplexes formed between amphiphilic poly(allylamine) (PAA) and insulin were
      prepared, characterised and the impact of polymer architecture on the protection
      of insulin against three enzymes was investigated. PAA previously modified with
      either cetyl or cholesteryl pendant groups at two levels of hydrophobic grafting
      and its quaternised derivatives were used to produce polymer-insulin
      nanocomplexes. Transmittance study, differential scanning calorimetry,
      hydrodynamic size and zeta potential measurement were conducted and the
      morphology of the complexes were visualised using transmission electron
      microscopy. All polymers were found to have an optimal polymer to insulin ratio
      of 0.4:1 mg mL(-1) with particle size ranging from 88 to 154 nm. Polymer
      architecture has an impact on the morphology of the complexes produced but has
      little influence on the complexation efficiency (CE). Almost all polymers were
      unable to produce complexes with a CE of above 50%. Most polymers demonstrated an
      ability to reduce insulin degradation by trypsin while the polymer architecture
      plays a pivotal role against alpha-chymotrypsin and pepsin degradation.
      Quaternised cholesteryl polymers were able to significantly limit insulin
      degradation by alpha-chymotrypsin while cetyl polymers were particularly
      effective against pepsin degradation. These results indicated that a combination
      of polymers might be required to enhance protection against all three proteolytic
      enzymes for efficacious oral delivery of insulin.

PMID- 19766179
TI  - The initial release of cisplatin from poly(lactide-co-glycolide) microspheres.
AB  - PLGA microspheres loaded with cisplatin were produced using a single emulsion
      method. A semi-empirical model, with bi-exponential terms, was found to give a
      better fit to the drug release profiles compared to a mono-exponential model.
      This model suggests that there are two separate fractions of drug present in the
      depot. A fraction of the drug is located near/at the surface of the depot, and is
      readily released during immersion in buffer. A second fraction of drug is
      entrapped deeper within the depot and is subsequently released. It was also found
      that the initial release of cisplatin from PLGA microsphere is highly diffusion
      controlled and the classical Higuchi model provides a good fit. From studies of
      water diffusion using PFG-NMR, results suggested that 50:50 PLGA microsphere was
      most susceptible to swelling and this might have promoted the faster initial drug
      release. Results from NMR cryoporometry also indicated that the developed PLGA
      microspheres could have "ink-bottle" pores.

PMID- 19766180
TI  - The influence of postoperative tissue formation on sound transmission after
      stapes surgery.
AB  - In the surgical treatment of otosclerosis, the coupling between the stapes
      prosthesis and the long process of the incus is critical. After surgery,
      connective tissue and mucosa may grow over the coupling area and thereby
      influence the sound transmission properties of the incus-prosthesis interface. It
      was the hypothesis of this study that tissue ongrowth in the incus-prosthesis
      interface has little influence on sound transmission following stapes surgery.
      The goals of the study were to: (1) investigate the extent of postoperative
      tissue ongrowth over the stapes prosthesis; (2) objectively evaluate intra- and
      postoperative sound transmission properties of revision stapes surgery and
      compare the findings to those from primary surgery; (3) quantify the influence of
      ongrown tissue on sound transmission after stapes surgery. A group of 10 patients
      undergoing revision stapes surgery was investigated with audiological evaluations
      and intraoperative laser Doppler interferometry, and with scanning electron
      microscopy of the explanted incus with its adherent prosthesis in 6 patients.
      Results were compared to a group of patients undergoing primary otosclerosis
      surgery and temporal bone experiments. Results indicated that tissue grows over
      the prosthesis, as identified in all specimens. Sound transmission properties
      were evaluated intraoperatively (i.e., incus mobility and prosthesis-fixation
      quality), and found to correlate well with the functional hearing results.
      Ongrowing mucosa in the incus-prosthesis interface had only a minimal effect on
      sound transmission properties and cannot compensate adequately for insufficient
      prosthesis fixation. Therefore, it is essential that the stapes prosthesis is
      properly fixed during primary otosclerosis surgery.

PMID- 19766181
TI  - Cytomegalovirus and immune senescence: culprit or innocent bystander?
AB  - Immune senescence may be defined as the age-related reduction and dysregulation
      of immune function, and has been associated with increased incidence and severity
      of infectious diseases and with poor efficacy of prophylactic vaccines in the
      elderly. Several studies have demonstrated that persistent infections with Herpes
      viruses in general and Cytomegalovirus (CMV) in particular have a profound
      influence on subset distribution, phenotype and potentially also on the function
      of T cells in ageing individuals. The association of CMV-seropositivity and
      accumulation of CMV-specific CD8+ T cells with decreased survival in longitudinal
      studies of very elderly has fostered the hypothesis that CMV-infection may be an
      important causative factor for the development of immune senescence. Here, we
      have critically summarized the current body of evidence supporting this
      hypothesis, highlight some controversial issues about its relevance and
      mechanisms and propose areas of future research to demonstrate unequivocally
      whether and how persistent infections might compromise the ageing immune system.

PMID- 19766182
TI  - Importance of neural mechanisms in colonic mucosal and muscular dysfunction in
      adult rats following neonatal colonic irritation.
AB  - Previous studies have shown that early life trauma induced by maternal separation
      or colonic irritation leads to hypersensitivity to colorectal distension in
      adulthood. We tested the hypothesis that repetitive colorectal distension in
      neonates leads to abnormalities in colonic permeability and smooth muscle
      function in the adult rat. In neonatal rats, repetitive colorectal distension was
      performed on days 8, 10, and 12. As adults, stool consistency was graded from 0
      (formed stool) to 3 (liquid stool). Colonic tissue was isolated for histology and
      myeloperoxidase levels. The colonic mucosa was placed in modified Ussing chambers
      for measurements of permeability and short-circuit current responses to
      forskolin, electrical field stimulation, and carbachol. Segments of colonic
      musculature were placed in organ baths and contractile response to potassium
      chloride, electrical field stimulation, and carbachol were determined. In adult
      rats that experienced neonatal colonic irritation, no significant changes in
      colonic histology or myeloperoxidase activity were observed; however, stool
      consistency scores were increased. Mucosal permeability, measured as an increase
      in basal conductance, was significantly increased but no changes in short-circuit
      current responses were observed. In adulthood, rats that underwent colorectal
      distension as neonates exhibited an elevated smooth muscle contractile response
      to potassium chloride, but no changes in response to electrical field stimulation
      or carbachol. In summary, neonatal colonic irritation, shown previously to
      produce colonic hypersensitivity, leads to significant alterations in colonic
      mucosal and smooth muscle function characterized by loose stools, increased
      mucosal permeability, and increased smooth muscle contractility in the absence of
      colon inflammation in adulthood.

PMID- 19766183
TI  - Inhibition of the JNK/AP-1 pathway reduces neuronal death and improves behavioral
      outcome after neonatal hypoxic-ischemic brain injury.
AB  - Perinatal hypoxic-ischemic (HI) brain damage continues to be a major clinical
      problem. We investigated the contribution of the MAP kinase c-Jun N-terminal
      kinase (JNK), to neonatal HI brain damage. JNK regulates several transcriptional
      (via AP-1 activation) and non-transcriptional processes involved in brain damage
      such as inflammation and cell death/survival. P7 rats were subjected to HI by
      unilateral carotid artery occlusion and hypoxia. HI-induced activation of
      cerebral AP-1 peaked at 3-6h post-HI. Intraperitoneal administration of the JNK
      inhibitor TAT-JBD immediately after HI prevented AP-1 activation. TAT-JBD
      treatment within 3h after HI reduced early neuronal damage by approximately 30%.
      JNK/AP-1 inhibition did not reduce HI-induced cytokine/chemokine expression.
      Analysis of indicators of apoptotic cell death revealed that TAT-JBD markedly
      reduced the HI-induced increase in active caspase 3. However, the upstream
      mediators of apoptosis: active caspase 8, cleaved Bid, mitochondrial cytochrome c
      release and caspase 9 cleavage were not reduced after TAT-JBD. TAT-JBD inhibited
      the HI-induced increase in Smac/DIABLO, an inhibitor of IAPs that prevent
      activation of caspase 3. TAT-JBD treatment also reduced cleavage of alpha-fodrin,
      indicating that calpain-mediated brain damage was reduced. Neuroprotection by TAT
      JBD treatment was long-lasting as gray- and white matter damage was diminished by
      approximately 50% at 14 weeks post-HI concomitantly with marked improvement of
      sensorimotor behavior and cognitive functioning. In conclusion, JNK inhibition by
      TAT-JBD treatment reduced neonatal HI brain damage with a therapeutic window of
      3h and long-lasting anatomical and behavioral improvements. We propose that
      inhibition of mitochondrial Smac/DIABLO release and calpain activation contribute
      to neuroprotection by TAT-JBD.

PMID- 19766184
TI  - l-Theanine, an amino acid in green tea, attenuates beta-amyloid-induced cognitive
      dysfunction and neurotoxicity: reduction in oxidative damage and inactivation of
      ERK/p38 kinase and NF-kappaB pathways.
AB  - Amyloid beta (Abeta)-induced neurotoxicity is a major pathological mechanism of
      Alzheimer disease (AD). In this study, we investigated the inhibitory effect of l
      theanine, a component of green tea (Camellia sinensis), on Abeta(1-42)-induced
      neuronal cell death and memory impairment. Oral treatment of l-theanine (2 and 4
      mg/kg) for 5 weeks in the drinking water of mice, followed by injection of
      Abeta(1-42) (2 microg/mouse, icv), significantly attenuated Abeta(1-42)-induced
      memory impairment. Furthermore, l-theanine reduced Abeta(1-42) levels and the
      accompanying Abeta(1-42)-induced neuronal cell death in the cortex and
      hippocampus of the brain. Moreover, l-theanine inhibited Abeta(1-42)-induced
      extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein
      kinase as well as the activity of nuclear factor kappaB (NF-kappaB). l-Theanine
      also significantly reduced oxidative protein and lipid damage and the elevation
      of glutathione levels in the brain. These data suggest that the positive effects
      of l-theanine on memory may be mediated by suppression of ERK/p38 and NF-kappaB
      as well as the reduction of macromolecular oxidative damage. Thus, l-theanine may
      be useful in the prevention and treatment of AD.

PMID- 19766185
TI  - A comparison of BRCA1 nuclear localization with 14 DNA damage response proteins
      and domains: identification of specific differences between BRCA1 and 53BP1 at
      DNA damage-induced foci.
AB  - BRCA1 is an important mediator of the DNA damage response pathway. Previous
      studies have identified a number of proteins that associate with BRCA1 at nuclear
      foci after ionizing radiation (IR)-induced DNA damage. However, the co
      localization patterns of BRCA1 and various DNA damage response proteins have not
      yet been systematically quantified and compared within the same experimental
      system. In this study, a new inducible human cell line was established to allow
      unambiguous detection of YFP-BRCA1 at nuclear foci. Quantitative 2-D microscopic
      analysis was performed to compare the intranuclear co-localization of YFP-BRCA1
      with 10 cellular proteins and 4 cellular domains before and after IR.
      Intriguingly, YFP-BRCA1 displayed significantly better focal co-localization with
      BARD1, RAP80 and Abraxas than with the upstream foci-initiating proteins gamma
      H2AX and MDC1. In contrast to previous reports, we found that the co-localization
      between YFP-BRCA1 and 53BP1 foci was surprisingly weak. Quantitative analyses of
      3-D confocal images showed that approximately 60% of 53BP1 foci were unrelated to
      YFP-BRCA1 foci, approximately 35% of foci were abutting and only approximately 5%
      of foci co-localized. The YFP-BRCA1 and 53BP1 nuclear foci were distinctively
      separated within the first 3h after IR. In addition, in situ nuclear retention
      analysis revealed YFP-BRCA1 and BARD1 are less mobile than 53BP1 at IR-induced
      nuclear foci. Our findings indicate that BRCA1-BARD1 and 53BP1 are proximal but
      not overlapping at DNA break sites and are consistent with recent evidence for
      distinct roles of these proteins in the DNA damage response pathway.

PMID- 19766186
TI  - Molecular mobility in liquid and glassy states of telmisartan (TEL) studied by
      broadband dielectric spectroscopy.
AB  - The molecular relaxation in liquid and glassy states of Telmisartan (TEL) has
      been studied by Broadband Dielectric Spectroscopy (BDS) covering wide temperature
      and frequency range. Multiple relaxation processes were observed. Besides the
      primary alpha-relaxation, two secondary relaxations beta and gamma (labelled in
      order of decreasing time scale) have been reported. Well-separated beta-process
      observed above and below glass transition temperature T(g), has activation energy
      E(beta)=81.8 kJ/mol and was identified as intermolecular Johari-Goldstein (JG)
      process. The gamma-relaxation visible in dielectric loss spectra at very low
      temperatures is most likely non-JG relaxation. The temperature dependence of the
      relaxation times of alpha-process, measured over 11 orders of magnitude, cannot
      be described by a single Vogel-Fulcher-Tamman-Hesse (VFTH) equation. At
      temperature T(B)=475.8K the change in relaxation dynamics occurred, consequently
      a new set of VFTH parameters was required. From low temperature VFTH fits the
      glass transition temperature T(g) was estimated as T(g)=400.3 K and fragility
      index m=87 was calculated. Of particular interest was the time scale of molecular
      motion below the glass transition temperature. Our observation clearly indicates
      that the alpha-relaxation times at room temperature most probably would exceed 3
      years and amorphous TEL should maintain physically and chemically stable over
      prolonged storage time.

PMID- 19766187
TI  - Synergistic effects of Isatis tinctoria L. and tacrolimus in the prevention of
      acute heart rejection in mice.
AB  - Although immunosuppressive treatments are available for acute cardiac rejection
      no viable treatment exists for long-term cardiac graft failure. Moreover, the
      extended use of calcineurin inhibitor immunosuppressants, the mainstay of current
      treatment for cardiac transplantation, leads to significant side effects such as
      nephrotoxicity and an increased risk of cardiac disease. Because some agents used
      in Traditional Chinese Medicine (TCM) have strong immunosuppressive effects
      coupled with low toxicity, we investigated the effect of Compound K (K), the
      synthesized analogue of highly unsaturated fatty acids from Isatis tinctoria L.,
      either as a single treatment or combined with tacrolimus (FK-506) on acute
      cardiac allograft rejection. We compared the ability of K alone, or in
      combination with FK-506, to inhibit acute heart transplant rejection both in
      vitro and in vivo. We found that the inhibition of lymphocyte proliferation was
      positively correlated with K concentration. K significantly reduced IL-2 and IFN
      gamma expression levels and significantly inhibited lymphocyte proliferation in
      both a lymphocyte transformation test and a mixed lymphocyte reaction (MLR). We
      also found that the inhibitory effect of a combination of K and a sub-therapeutic
      dose of FK-506 (SubFK-506) was stronger than that of full-dose FK-506 alone. Oral
      administration of K reduced acute cardiac allograft rejection in mice and had no
      apparent toxicity. In vivo, the immunosuppressive effect of K combined with a
      half-dose of FK-506 was equivalent to that of a full-dose of FK-506 alone. K
      combined with a half-dose of FK-506 reduced the expression levels of IL-2 and IFN
      gamma (both within the graft and in the recipients' serum) more effectively than
      a full-dose of FK-506. These results show that K has significant
      immunosuppressive effects both in vitro and in vivo. When used as a combination
      therapy with FK-506 we see a powerful inhibition of rejection with no obvious
      toxic side effects. The mechanism of action is postulated to involve the
      inhibition of IL-2 and IFN-gamma expressions by lymphocytes, rather than the
      activation of Tr1 cells via the production of IL-10.

PMID- 19766188
TI  - Calculated withdrawal of low-dose immunosuppression based on a detailed
      immunological monitoring after kidney transplantation between monocygotic twins.
AB  - BACKGROUND: Pretransplant screening in living donor kidney transplantation
      includes human leukocyte antigen matching, and panel reactive antibody analysis,
      whereas T cell mediated anti-donor reactivity is not assessed routinely. We
      investigated T cell reactivity after living related kidney transplantation
      between two monocygotic twins and in consequence correlated the withdrawal of
      individual immunosuppressive medication with immunological findings. METHODS:
      Immunosuppression consisted of mycophenolate mofetil, glucocorticoid single shot,
      and induction therapy with antithymocyte immunoglobulin. RESULTS: FACS analysis
      of recipient peripheral blood cells revealed a normal haemogram after
      transplantation, showing non-activated CD4 and CD8 cells. Mixed lymphocyte
      reaction did not reveal donor-specific T cell activity. IFN-gamma and IL-10 ELISA
      of supernatants of recipient cells cocultivated with donor cells support the lack
      of Th1 and Th2 cell differentiation. CONCLUSION: Based on immunological findings
      on days 5 and 20 MMF-therapy was reduced and stopped. Immunological monitoring on
      day 90 confirmed the absence of immune reactions directed against donor tissue.

PMID- 19766189
TI  - Dopamine transporter glycosylation correlates with the vulnerability of midbrain
      dopaminergic cells in Parkinson's disease.
AB  - The dopamine transporter (DAT) is a membrane glycoprotein responsible for
      dopamine (DA) uptake, which has been involved in the degeneration of DA cells in
      Parkinson's disease (PD). Given that DAT activity depends on its glycosylation
      status and membrane expression, and that not all midbrain DA cells show the same
      susceptibility to degeneration in PD, we have investigated a possible
      relationship between DAT glycosylation and function and the differential
      vulnerability of DA cells. Glycosylated DAT expression, DA uptake, and DAT V(max)
      were significantly higher in terminals of nigrostriatal neurons than in those of
      mesolimbic neurons. No differences were found in non-glycosylated DAT expression
      and DAT K(m), and DA uptake differences disappeared after deglycosylation of
      nigrostriatal synaptosomes. The expression pattern of glycosylated DAT in the
      human midbrain and striatum showed a close anatomical relationship with DA
      degeneration in parkinsonian patients. This relationship was confirmed in rodent
      and monkey models of PD, and in HEK cells expressing the wild-type and a
      partially deglycosylated DAT form. These results strongly suggest that DAT
      glycosylation is involved in the differential vulnerability of midbrain DA cells
      in PD.

PMID- 19766190
TI  - Insights into the composition, morphology, and formation of the calcareous shell
      of the serpulid Hydroides dianthus.
AB  - To date, the calcareous tubes of serpulid marine worms have not been studied
      extensively in a biomineralization context. The structure and composition of the
      tube shell and adhesive cement of the marine tubeworm Hydroides dianthus were
      studied using a variety of characterization techniques, including powder XRD,
      FTIR, SEM, EDX, and AFM. The tube and cement were determined to be inorganic
      organic composite materials, consisting of inorganic aragonite (CaCO(3)) and Mg
      calcite ((Ca(0.8)Mg(0.2))CO(3)) crystals, and both soluble and insoluble organic
      matrices (SOM and IOM). SEM imaging revealed a variety of crystal morphologies.
      AFM nanoindentation of the inorganic components yielded Young's moduli of
      approximately 20GPa in the wet state, and approximately 50GPa in the dry state.
      Amino acid analysis of the SOM indicated substantial amounts of acidic and non
      polar neutral amino acids. Part of the insoluble organic tube lining was
      identified as being composed of collagen-containing fibres aligned in a criss
      crossed structure. The SOM and organic tube lining were found to contain
      carboxylated and sulphated polysaccharides. In an artificial seawater solution,
      the SOM and the organic tube lining mediated CaCO(3) mineralization in vitro.

PMID- 19766191
TI  - Influence of the g- conformation of Ser and Thr on the structure of transmembrane
      helices.
AB  - In order to study the influence of Ser and Thr on the structure of transmembrane
      helices we have analyzed a database of helix stretches extracted from crystal
      structures of membrane proteins and an ensemble of model helices generated by
      molecular dynamics simulations. Both complementary analyses show that Ser and Thr
      in the g- conformation induce and/or stabilize a structural distortion in the
      helix backbone. Using quantum mechanical calculations, we have attributed this
      effect to the electrostatic repulsion between the side chain Ogamma atom of Ser
      and Thr and the backbone carbonyl oxygen at position i-3. In order to minimize
      the repulsive force between these negatively charged oxygens, there is a modest
      increase of the helix bend angle as well as a local opening of the helix turn
      preceding Ser/Thr. This small distortion can be amplified through the helix,
      resulting in a significant displacement of the residues located at the other side
      of the helix. The crystal structures of aquaporin Z and the beta(2)-adrenergic
      receptor are used to illustrate these effects. Ser/Thr-induced structural
      distortions can be implicated in processes as diverse as ligand recognition,
      protein function and protein folding.

PMID- 19766192
TI  - Molecular characterization and expression analysis of nuclear oligomerization
      domain proteins NOD1 and NOD2 in grass carp Ctenopharyngodon idella.
AB  - Nuclear oligomerization domains (NODs) are cytosolic pattern recognition
      receptors (PRRs) to detect bacterial component. In this study, the molecular
      cloning and genomic characterization of grass carp NOD1 (gcNOD1) and grass carp
      NOD2 (gcNOD2) were reported. The complete open reading frame of gcNOD1 contains
      2814 bp, encoding a 937-amino acid polypeptide. The gcNOD2 cDNA sequence encodes
      982-amino acid polypeptide. Both gcNOD1 and gcNOD2 possess three conserved
      domains: carboxy terminal leucine rich repeat (LRR) domains, a central NOD, NBS
      or NACHT domain, and an amino terminal CARD domain (two in the case of NOD2). At
      the genomic level, gcNOD1 consists of 11 exons, with 10 intervening introns,
      spanning approximately 9 kb of genomic sequence. Whereas gcNOD2 has a length of
      approximately 5 kb with 9 intervening introns. Real time PCR analysis showed
      gcNOD1 and gcNOD2 were ubiquitously expressed in adult tissues. The highest
      transcript level of gcNOD1 was detected in brain, but in head kidney for gcNOD2.
      Grass carp reovirus significantly induced the expression of gcNOD1 and gcNOD2 in
      spleen (from days 1 to 6). However, expression profiles differed in time course
      response. Induction experiments with lipopolysaccharide (LPS), peptidoglycan
      (PGN) and polyI:C revealed the differential expression and regulation of gcNOD1
      and gcNOD2 in blood, head kidney, trunk kidney and spleen. All these data suggest
      a potential role of NOD1 and NOD2 in fish innate immune protection to bacterial
      and virus infections.

PMID- 19766193
TI  - In situ localisation of major histocompatibility complex class I and class II and
      CD8 positive cells in infectious salmon anaemia virus (ISAV)-infected Atlantic
      salmon.
AB  - It is assumed that the mobilisation of a strong cellular immune response is
      important for the survival of Atlantic salmon infected with infectious salmon
      anaemia virus (ISAV). In this study, the characterisation of immune cell
      populations in tissues of non-ISAV infected Atlantic salmon and during the early
      viraemia of ISAV was undertaken. Immunohistochemical investigations of spleen,
      head kidney and gills using monoclonal antibodies against recombinant proteins
      from MHC I, II and CD8 were performed on tissues from Atlantic salmon collected
      day 17 post-challenge in a cohabitant infection model. The localisations of MHC I
      and II in control salmon were consistent with previous reports but this study
      presents novel observations on the distribution of CD8 labelled cell populations
      in Atlantic salmon including the description of significant mucosal populations
      in the gills. The distribution of MHC I, MHC II and CD8 positive cell populations
      differed between control salmon and cohabitant salmon in the early stages of ISAV
      infection. The changes in MHC I labelled cells differed between organs in ISAV
      cohabitants but all investigated organs showed a decreased presence of MHC II
      labelled cells. Together with a clustering of CD8 labelled cells in the head
      kidney and a reduced presence of CD8 labelled cells in the gills, these
      observations support the early mobilisation of cellular immunity in the response
      of Atlantic salmon to ISAV infection. However, differences between the present
      study and the findings from studies investigating immune gene mRNA expression
      during ISAV infection suggest that viral strategies to interfere with protein
      expression and circumvent the host immune response could be operative in the
      early response to ISAV infection.

PMID- 19766194
TI  - Molecular cloning and characterization of lipopolysaccharide- and beta-1,3-glucan
      binding protein from the giant freshwater prawn Macrobrachium rosenbergii and its
      transcription in relation to foreign material injection and the molt stage.
AB  - Lipopolysaccharide (LPS)- and beta-1,3-glucan-binding protein (LGBP)
      complementary (c)DNA was cloned from the hepatopancreas of the giant freshwater
      prawn Macrobrachium rosenbergii using oligonucleotide primers and a reverse
      transcription polymerase chain reaction (RT-PCR). Both 3'- and 5'-regions were
      isolated by the rapid amplification of cDNA ends (RACE) method. Analysis of the
      nucleotide sequence revealed that the cDNA clone has an open reading frame of
      1389 bp encoding a protein of 378 amino acids (aa) including a 15-aa signal
      peptide. The calculated molecular mass of the mature protein (363 aa) was 41.2
      kDa with an estimated pI of 4.73. The M. rosenbergii LGBP sequence contains (1)
      three putative integrin-binding motifs, (2) a glucanase motif, (3) a putative N
      glycosylation site, (4) four protein kinase C phosphorylation sites, (5) four
      casein kinase II phosphorylation sites, and (6) a putative recognition motif.
      Sequence comparison showed that the deduced amino acids of LGBP of M. rosenbergii
      had overall similarities of 60-71% to those of known crustacean LGBPs and beta
      1,3-glucan-binding proteins (BGBPs). The LGBP of M. rosenbergii was mainly
      expressed in the hepatopancreas. The LGBP transcript of M. rosenbergii was
      downregulated in haemocytes, but was upregulated in the hepatopancreas when
      injected with LPS and poly:IC after 12 h. The LGBP messenger (m)RNA expression of
      prawns in the postmolt stage was significantly upregulated in haemocytes, but
      downregulated in the hepatopancreas, which revealed a complementary relationship
      between haemocytes and the hepatopancreas in the molt cycle.

PMID- 19766195
TI  - An acyl-CoA-binding protein (FcACBP) and a fatty acid binding protein (FcFABP)
      respond to microbial infection in Chinese white shrimp, Fenneropenaeus chinensis.
AB  - Acyl-CoA-binding protein (ACBP) and fatty acid-binding protein (FABP) are
      involved in lipid metabolism. ACBP plays a key role in multiple cellular tasks
      including modulation of fatty acid biosynthesis, enzyme regulation, vesicular
      trafficking, and gene regulation. In our study, a 536 bp cDNA of ACBP (FcACBP)
      was cloned and identified as a widely distributed gene in the Chinese white
      shrimp, Fenneropenaeus chinensis. Its expression in intestine was upregulated in
      response to white spot syndrome virus (WSSV) or Vibrio anguillarum infection. The
      expression patterns were confirmed by Western blot analysis. FABPs, members of
      the lipid-binding protein superfamily, play an important role in lipid metabolism
      and also participate in vertebrate innate immunity. A cDNA of FABP (FcFABP)
      cloned from the hepatopancreas of the shrimp was 715 bp in size and encoded a 14
      kDa protein. FcFABP appeared to be a basic fatty acid binding protein with a
      predicted isoelectric point of 9.16. It showed sequence similarity to both
      vertebrate and invertebrate FABPs. Phylogenetic analysis showed that FcFABP,
      together with LvFABP, were clustered into one group. FcFABP was detected mainly
      in the hepatopancreas and expression level increased after a challenge with WSSV.
      FcFABP was down-regulated by V. anguillarum challenge. The protein also had
      bacterial binding activity. These two lipid metabolism related proteins may play
      important roles in shrimp innate immunity.

PMID- 19766196
TI  - A topology-preserving approach to the segmentation of brain images with multiple
      sclerosis lesions.
AB  - We describe a new fully automatic method for the segmentation of brain images
      that contain multiple sclerosis white matter lesions. Multichannel magnetic
      resonance images are used to delineate multiple sclerosis lesions while
      segmenting the brain into its major structures. The method is an atlas-based
      segmentation technique employing a topological atlas as well as a statistical
      atlas. An advantage of this approach is that all segmented structures are
      topologically constrained, thereby allowing subsequent processing such as
      cortical unfolding or diffeomorphic shape analysis techniques. Evaluation with
      both simulated and real data sets demonstrates that the method has an accuracy
      competitive with state-of-the-art MS lesion segmentation methods, while
      simultaneously segmenting the whole brain.

PMID- 19766197
TI  - Evolutionary pattern and process within the Vertigo gouldii (Mollusca: Pulmonata,
      Pupillidae) group of minute North American land snails.
AB  - A phylogenetic analysis of 19 sibling taxa in the Vertigo gouldii group was
      conducted on 73 individuals sampled across North America using DNA sequence data
      of the mitochondrial genes cytochrome oxidase subunit 1 (CO1) and 16S ribosomal
      RNA (16S), and the internal transcribed spacer-2 of the nuclear ribosomal RNA
      (ITS-2) gene. The results of these analyses were found incongruent with previous
      taxonomic concepts used to define the V. gouldii group and its composite taxa
      that were based entirely on conchological features. The mtDNA sequence data
      suggest that some previous members of the traditional V. gouldii group may be
      more closely related to V. modesta. They also suggest that V. gouldii may itself
      consist of seven species-level branches spread across two deeply rooted clades.
      Revision of geographical distributions on the basis of these analyses suggests
      that these Vertigo species may commonly possess continental-sized ranges in spite
      of their minute size and limited active dispersal ability. High levels of
      sympatry within the group are also confirmed, with up to four species being known
      to co-occur within single microsites. These data also suggest that rates of
      diversification have been non-constant. Assuming a 1%/my rate of base pair
      substitution, a 10-fold diversification pulse is indicated from 6.7-7.0 myBP,
      which would be co-incident with known mid-late Miocene global climate changes.

PMID- 19766198
TI  - Livistona palms in Australia: ancient relics or opportunistic immigrants?
AB  - Eighteen of the 34 species of the fan palm genus Livistona (Arecaceae) are
      restricted to Australia and southern New Guinea, east of Wallace's Line, an
      ancient biogeographic boundary between the former supercontinents Laurasia and
      Gondwana. The remaining species extend from SE Asia to Africa, west of Wallace's
      Line. Competing hypotheses contend that Livistona is (a) ancient, its current
      distribution a relict of the supercontinents, or (b) a Miocene immigrant from the
      north into Australia as it drifted towards Asia. We have tested these hypotheses
      using Bayesian and penalized likelihood molecular dating based on 4Kb of nuclear
      and chloroplast DNA sequences with multiple fossil calibration points. Ancestral
      areas and biomes were reconstructed using parsimony and maximum likelihood. We
      found strong support for the second hypothesis, that a single Livistona ancestor
      colonized Australia from the north about 10-17Ma. Spread and diversification of
      the genus within Australia was likely favoured by a transition from the aseasonal
      wet to monsoonal biome, to which it could have been preadapted by fire-tolerance.

PMID- 19766199
TI  - Chronic administration of troxerutin protects mouse brain against D-galactose
      induced impairment of cholinergic system.
AB  - Previous evidence showed that administration of d-galactose (d-gal) increased ROS
      production and resulted in impairment of cholinergic system. Troxerutin, a
      natural bioflavonoid, has been reported to have many benefits and medicinal
      properties. In this study, we evaluated the protective effect of troxerutin
      against d-gal-induced impairment of cholinergic system, and explored the
      potential mechanism of its action. Our results displayed that troxerutin
      administration significantly improved behavioral performance of d-gal-treated
      mice in step-through test and morris water maze task. One of the potential
      mechanisms of this action was decreased AGEs, ROS and protein carbonyl levels in
      the basal forebrain, hippocampus and front cortex of d-gal-treated mice.
      Furthermore, our results also showed that troxerutin significantly inhibited
      cholinesterase (AchE) activity, increased the expression of nicotinic
      acetylcholine receptor alpha 7 (nAchRalpha7) and enhanced interactions between
      nAchRalpha7 and either postsynaptic density protein 95 (PSD95) or N-methyl-d
      aspartate receptors subunit 1 (NMDAR1) in the basal forebrain, hippocampus and
      front cortex of d-gal-treated mice, which could help restore impairment of brain
      function.

PMID- 19766200
TI  - Differential effects of MDMA and scopolamine on working versus reference memory
      in the radial arm maze task.
AB  - Previous research has suggested that the disruption to memory-task performance
      seen following acute exposure to 3,4-methylenedioxymethaphemtamine (MDMA) with
      rats might best be characterized as reference memory impairment rather than a
      working memory impairment. The current study specifically compared the effects of
      MDMA and scopolamine on measures of working versus reference memory in an eight
      arm radial maze task. It was predicted that scopolamine would produce a greater
      impairment with respect to the working memory component of the task, whereas MDMA
      would produce a greater impairment to reference memory. On each trial rats were
      allowed to make a total of four arm visits in order to collect the reinforcers
      located at the end of different arms in the maze. Working memory errors were
      indicated by re-visiting an already visited arm during a trial, whereas visiting
      an arm that was never baited on any trial indicated a reference memory error.
      Using a within subjects design, rats were exposed to a range of doses of
      scopolamine and MDMA administered acutely. An interaction between drug type and
      memory error type was found. Specifically, scopolamine produced more working
      memory errors than reference memory errors, while MDMA produced the opposite
      pattern of significantly more reference memory errors compared to working memory
      error. This finding supported the hypothesis that MDMA disrupts reference memory
      processes in terms of an impairment in the strategies or rules used for solving
      memory tasks.

PMID- 19766201
TI  - E versus Z geometry in beta-D-arabino-hexopyranosidulose oximes.
AB  - Koenigs-Knorr-type glycosidations of peracylated 2Z-benzoyloxyimino
      glycopyranosyl bromides invariably proceed with retention of the Z-geometry.
      Accordingly, the many beta-D-hexosidulose oximes in literature which were
      prepared in this way and for which the oxime geometry has not been addressed
      explicitly, are the Z-oximes throughout. By contrast, oximation of beta-D
      hexopyranosid-2-uloses leads to mixtures of E and Z oximes readily separable and
      structurally verifiable by (1)H and (13)C NMR. Configurational assignments rested
      on comparative evaluation of NMR data of E and Z isomers, and, most notably on an
      X-ray structural analysis of the pivaloylated isopropyl 2E-benzoyloxyimino-2
      deoxy-beta-D-arabino-hexopyranoside revealing the unusual (1)S(5)<==>(1,4)B
      conformation for the pyranoid ring.

PMID- 19766202
TI  - Lipoic acid attenuates high fat diet-induced chronic oxidative stress and
      immunosuppression in mice jejunum: a microarray analysis.
AB  - A high fat diet (HFD) has long been linked to immune dysfunction, including
      diminished numbers or reactivity of lymphocytes, increased susceptibility to
      infection, inhibited lymphocytes function during antigen-specific responses and
      developed oxidative stress. Whereas the molecular mechanistic events associated
      with immune deficiency remain to be fully determined. Using the DNA microarray
      system, we analyzed the gene expression patterns of lymphocyte related signal
      transduction proteins in jejunum of C57BL/6 mice in order to gain insight on the
      possible molecular mechanism by which HFD induced oxidative stress effects on
      signal transduction of lymphocytes. Results of present study showed that HFD
      induced oxidative stress and immunosuppression in jejunum. Antioxidant lipoic
      acid (LA) supplement ameliorated that HFD induced oxidative stress and
      immunosuppression by recovering transcriptional levels of the gene involved in B
      cell receptor, T cell differentiation signaling pathway, and free radical
      scavengers. The present study indicates that a HFD can induce chronic oxidative
      stress, suppress signal transduction of gut-associated lymphocytes, and lead to
      an inhibition of mucosal immunity.

PMID- 19766203
TI  - Abraham Lincoln and Harry Potter: children's differentiation between historical
      and fantasy characters.
AB  - Based on the testimony of others, children learn about a variety of figures that
      they never meet. We ask when and how they are able to differentiate between the
      historical figures that they learn about (e.g., Abraham Lincoln) and fantasy
      characters (e.g., Harry Potter). Experiment 1 showed that both younger (3- and 4
      year-olds) and older children (5-, 6-, and 7-year-olds) understand the status of
      familiar figures, correctly judging historical figures to be real and fictional
      figures to be pretend. However, when presented with information about novel
      figures embedded in either a realistic narrative or a narrative with obvious
      fantasy elements, only older children used the narrative to make an appropriate
      assessment of the status of the protagonist. In Experiment 2, 3-, and 4-year-olds
      were prompted to judge whether the story events were really possible or not.
      Those who did so accurately were able to deploy that judgment to correctly assess
      the status of the protagonist.

PMID- 19766204
TI  - Precisely wrong? The problems with the Jones and Martin genetic model of sex
      differences in handedness and language lateralisation.

PMID- 19766206
TI  - FIGO guidelines for training residents and fellows in urogynecology, female
      urology, and female pelvic medicine and reconstructive surgery.

PMID- 19766207
TI  - Pregnancy and perinatal outcome in women with hyperthyroidism.
AB  - OBJECTIVE: To investigate pregnancy outcome for patients with treated
      hyperthyroidism. METHODS: A population-based study was performed comparing all
      singleton pregnancies of women with and women without hyperthyroidism at the
      Soroka University Medical Center, Be'er-Sheva, Israel, between January 1988 and
      January 2007. Stratified analysis, using a multiple logistic regression model,
      was performed to control for confounders. RESULTS: During the study period, there
      were 185636 singleton deliveries in the medical center. Of these, 189 (0.1%) were
      from women with hyperthyroidism. Using multivariate analysis with backward
      elimination, the following risk factors were significantly associated with
      hyperthyroidism: placental abruption; cesarean delivery; and advanced maternal
      age. No significant differences regarding perinatal outcome were noted between
      the groups. Women with hyperthyroidism had significantly higher rates of cesarean
      delivery than did women without hyperthyroidism (20.1% vs 13.1%; P<0.004), even
      after controlling for confounders. CONCLUSIONS: Treated hyperthyroidism was not
      associated with adverse perinatal outcome. However, hyperthyroidism was found to
      be an independent risk factor for cesarean delivery.

PMID- 19766208
TI  - Maternal and perinatal outcomes of visceral leishmaniasis (kala-azar) treated
      with sodium stibogluconate in eastern Sudan.
AB  - OBJECTIVE: To investigate maternal and perinatal outcomes when pregnant women
      with visceral leishmaniasis (VL, also known as kala-azar) are treated with the
      antimonial sodium stibogluconate. METHOD: Forty-two pregnant women with VL were
      treated with sodium stibogluconate at Gadarif Hospital, Gadarif, Sudan, and
      mother and child were followed up for 1 year. RESULTS: The treatment began at a
      mean+/-SD of 24.4+/-9.2 weeks of pregnancy. None of the patients had malaria or
      HIV. Two (4.7%) who received the treatment in the first trimester had
      miscarriages; 4 (4.9%) died from hepatic encephalopathy during the second week of
      treatment; and 2 (4.7%) had preterm deliveries. One of the newborns had a
      myelomeningocele and died at 2 hours, and the other died from VL at 2 months.
      CONCLUSION: Preventive measures against VL should be employed in the region, and
      more research on VL and its treatment during pregnancy is needed.

PMID- 19766209
TI  - The role of family history in clinical symptoms and therapeutic outcomes of women
      with polycystic ovary syndrome.
AB  - OBJECTIVE: To investigate the association between family history and clinical
      symptoms of polycystic ovary syndrome (PCOS) that were thought to be inherited,
      by treating women with PCOS with contraceptive pills and metformin, and assessing
      outcomes. METHODS: Of 164 women with PCOS, 49 with menstrual abnormalities,
      hyperandrogenism, and abnormal glucose and/or insulin levels underwent a 3-month
      treatment with contraceptive pills and metformin. Family history was taken, and
      physical and ultrasound examinations were performed. Serum levels of glucose,
      insulin, lipoproteins, lipids, and reproductive hormones were measured before and
      after treatment. RESULTS: The serum levels of low-density lipoprotein, total
      cholesterol, apolipoprotein B, and triglycerides were higher in the patients with
      a family history of the studied symptoms than in those with no such family
      history. After treatment, changes in testosterone and glucose levels, glucose
      area under curve, and homeostasis model assessment value differed in the 2
      groups. CONCLUSION: The patients with a family history of PCOS symptoms thought
      to be inherited were more sensitive to oral contraceptive and metformin
      treatment.

PMID- 19766210
TI  - [Pseudo-intestinal intussusception: Rapunzel syndrome].

PMID- 19766211
TI  - [Esophageal perforation during nasogastric tube insertion in a patient with right
      sided aortic arch and thoracic aorta. Pathophysiology and surgical implications].
AB  - Esophageal perforation during nasogastric tube insertion is a very unusual
      occurrence. In this case report, radiologic images revealed a right-sided aortic
      arch with a right-sided thoracic aorta. This anatomical anomaly probably
      contributed to the complication and necessitated a modified approach to the
      surgical repair.

PMID- 19766212
TI  - [Aortic rupture due to a swallowed medical needle].

PMID- 19766213
TI  - [Laparoscopic splenectomy: indications, techniques, outcomes].
AB  - Laparoscopic splenectomy (LS) has become the standard approach to splenectomy for
      benign and malignant hematologic diseases despite a paucity of high-level
      evidence. The procedure requires expertise in laparoscopic surgical techniques
      and meticulous dissection of the spleen. Management should include a preoperative
      radiologic assessment to measure splenic volume and to detect the presence of
      accessory splenic tissue; the patient should undergo preoperative vaccination
      against meningococcal, pneumococcal, and Haemophilus influenzae type B
      infections. Prophylactic antibiotics are used in the perioperative period as well
      as prophylactic anticoagulation therapy which may be continued long-term in high
      risk patients. LS is associated with a low morbidity and mortality; when compared
      to laparotomy, it reduces the length of hospital stay and improves the quality of
      life by decreasing postoperative ileus and pain. There are a variety of
      laparoscopic approaches; the hand-assisted technique and newer coagulating
      devices have facilitated the operative technique leading to increasing acceptance
      of laparoscopy as the preferred approach - even in patients with malignant
      hematologic disease and/or massive splenomegaly.

PMID- 19766214
TI  - [Is laparoscopic gastric bypass a dangerous procedure during the early phase of
      the learning curve? A prospective study of the first 50 cases].
AB  - BACKGROUND: Among the various bariatric procedures, laparoscopic Roux-en-Y
      gastric bypass (LRYGBP) is widely considered to be the gold standard. However, a
      majority of bariatric surgeons in France do not perform LFYGBP, perhaps because
      of its reputation as a technically demanding procedure with a long learning
      curve. This study evaluates the outcomes and the learning curve for the first 50
      LFYGBP performed by one surgeon in a French non-university hospital. MATERIAL AND
      METHOD: Between April 2007 and February 2009, we performed our first 50 cases of
      LRYGBP. Surgical outcomes and the learning curve were measured by prospective
      criteria including length of stay, operative time, complications, percentage
      weight loss and reduction of obesity-related co-morbidities. RESULTS: The mean
      patient age was 41.8+/-9.8 years. The mean BMI was 47.7+/-7.1 kg/m(2). The mean
      operative time was 146+/-51 minutes and the mean hospital stay was 5.3+/-1.4
      days. Three cases (6%) were converted to open surgery. Early complications
      occurred in 4% and late complications occurred in 6%. The average follow-up was
      6.3+/-1.3 months. Overall excess weight loss was 39.5, 50, 62, and 63% at 3, 6,
      9, and 12 months. CONCLUSION: LRYGBP can be performed with acceptable morbidity
      and short-term results, even during the early phase of a surgeon's learning
      curve. It is a feasible procedure for bariatric surgeons with previous experience
      in gastric banding.

PMID- 19766215
TI  - [Is strangulated obturator hernia still a clinical diagnosis?].

PMID- 19766216
TI  - [Utero-enteric fistula due to obstetrical trauma: a case report].

PMID- 19766217
TI  - Associations of inflammatory markers with coronary artery calcification: results
      from the Multi-Ethnic Study of Atherosclerosis.
AB  - OBJECTIVE: Inflammatory markers predict coronary heart disease (CHD). However,
      associations with coronary artery calcium (CAC), a marker of subclinical CHD, are
      not established. METHODS: We examined cross-sectional associations of C-reactive
      protein (CRP), interleukin-6 (IL-6) and fibrinogen with CAC presence (Agatston
      score>0 by computed tomography) in 6783 Multi-Ethnic Study of Atherosclerosis
      (MESA) participants. RESULTS: In all participants, those in the highest, compared
      to lowest, quartile of CRP had a relative risk (RR, 95% confidence interval) of
      1.13 (1.06-1.19; p<0.01) for CAC in age, sex and ethnicity adjusted models. For
      highest versus lowest quartiles, relative risks were 1.22 (1.15-1.30; p<0.01) for
      IL-6 and 1.18 (1.11-1.24; p<0.01) for fibrinogen. Adjusting for CHD risk factors
      (smoking, diabetes, blood pressure, obesity and dyslipidemia) attenuated RRs. RRs
      for CAC were 1.05 (0.99-1.12; p=0.63) for CRP, 1.12 (1.06-1.20; p<0.01) for IL-6
      and 1.09 (1.02-1.16; p=0.01) for fibrinogen in multivariable adjusted models.
      Results were similar for men and women and across ethnic groups. CONCLUSION:
      Inflammatory markers were weakly associated with CAC presence and burden in MESA.
      Our data support the hypothesis that inflammatory biomarkers and CAC reflect
      distinct pathophysiology.

PMID- 19766218
TI  - Levels of lipids and apolipoproteins in three cultures.
AB  - OBJECTIVE: A complete lipoprotein profile requires measurement of the major
      plasma apolipoproteins-apoB and apoA-I-in addition to measurement of the major
      plasma and lipoprotein lipids. The objective of this study was to demonstrate the
      additional information that can be acquired by comparing the major plasma lipids
      and apolipoproteins amongst adult male and female Swedes, Iranians and Americans.
      METHODS: Data on Iranians were derived from the Isfahan Healthy Heart Program, a
      prospective community-based sample of 12,103 individuals >20 years of age. Data
      on Swedes were derived from the AMORIS study, a prospective epidemiological study
      of 173,629 subjects. Data on Americans were derived from the NHANES III, data
      bank, which is designed to be representative of the adult American population.
      Lipids were measured by conventional methods. ApoB and apoA-I were measured by
      IFCC/WHO standardized methods. RESULTS AND CONCLUSIONS: There is a complex
      pattern of differences amongst the cultures. There are also important
      similarities in the differences between the genders. Swedes have the highest
      levels of LDL-C (3.77 mmol/L), apoB (1.27 g/L) and HDL-C (1.53 mmol/L) but the
      lowest levels of triglyceride (1.47 mmol/L for the Swedes vs. 1.55 mmol/L and
      1.93 mmol/L for the Americans and Iranians, respectively, all p<0.001). Americans
      have higher levels of LDL-C than Iranians (3.26 mmol/L vs. 3.09 mmol/L, p<0.001)
      but lower levels of apoB (1.04 g/L vs. 1.14 g/L, p<0.001). The absolute values
      for both HDL-C and apoA-I are higher in females than males of all three cultures
      throughout the population distribution. The levels of the atherogenic
      lipoproteins peak between 30 and 40 in males but continue to rise in females. The
      apoB/apoA-I ratio is highest in the Swedes (0.92, p<0.001) but similar in the
      Americans and Iranians (0.81 and 0.80, respectively, p NS). By contrast, the
      TC/HDL-C ratio is highest in the Iranians, intermediate in the Americans and
      lowest in the Swedes (4.41 vs. 4.36 vs. 4.22, all p<0.001). These data provide
      further evidence that complete characterization of lipoproteins requires
      measurement of apoB and apoA-I as well as lipoprotein lipids and that the changes
      in plasma lipoproteins over time differ between the genders.

PMID- 19766219
TI  - Circulating markers of inflammation and endothelial dysfunction in Arab
      adolescent subjects: reference ranges and associations with age, gender, body
      mass and insulin sensitivity.
AB  - INTRODUCTION: Important biochemical markers for the low-grade vascular
      inflammation and endothelial dysfunction that characterize the earliest events in
      the pathogenesis of atherosclerosis are CRP and the adhesion molecules ICAM-1 and
      VCAM-1. This study aims to evaluate, in healthy Arab adolescent subjects aged 10
      19 yr, the reference ranges for these markers and their associations with such
      determinants as age, gender, body mass and insulin sensitivity. METHODS: There
      were 774 Kuwaiti subjects (316 boys and 456 girls) aged mean (SD) 14.5 (2.2) yr.
      All had detailed clinical examination, anthropometry (to derive BMI) and
      assessment of fasting serum levels of CRP, ICAM-1, VCAM-1 and insulin (and HOMA
      IR) to derive their reference values. Associations with putative determinants
      were explored by logistic regression analyses. RESULTS AND DISCUSSION: The
      reference ranges (mean (SD)) were: CRP 0.28 (0.49) mg/dl; ICAM-1, 286 (119)ng/ml;
      VCAM-1, 1148 (352)ng/ml; HOMA-IR, 4.57 (5.05). These parameters were
      significantly higher in boys than in girls, and in the overweight/obese and those
      aged < or =14 yr. BMI was significantly and independently related to CRP and ICAM
      1 even after adjusting for age, gender, socio-demographic factors, diet and
      exercise. Levels of these markers were significantly influenced by age and
      gender. CONCLUSION: BMI, age and gender are significant predictors of serum
      levels of circulating inflammatory biomarkers, particularly ICAM-1, CRP and HOMA
      IR. These atherogenic processes therefore probably cluster together in early life
      in individuals at increased later heart disease risk. Preventive public health
      measures should therefore commence in early childhood.

PMID- 19766220
TI  - Synergistic action of static stretching and BMP-2 stimulation in the osteoblast
      differentiation of C2C12 myoblasts.
AB  - Static stretching is a major type of mechanical stimuli utilized during
      distraction osteogenesis (DO), a general surgical method for the lengthening of
      bone. The molecular signals that drive the regenerative process in DO include a
      variety of cytokines. Among these, bone morphogenic protein (BMP, -2 and -4) has
      been reported to exhibit strongly enhanced expression following the application
      of mechanical strain during the distraction phase. We hypothesize that mechanical
      stretching enhances osteoblast differentiation in DO by means of interaction with
      BMP-2 induced cytokine stimulation. C2C12 pluripotential myoblasts were exposed
      to stretching load and the resulting cell proliferation and osteoblast
      differentiation were then examined. The application of static stretching force
      resulted in significant cell proliferation at day 3, although with variable
      intensity according to the magnitude of stretching. A combined treatment of
      stretching load with BMP-2 stimulation significantly increased alkaline
      phosphatase (ALP) activity and up-regulated the gene expression of osteogenic
      markers (ALP, type I collagen, osteopontin, osteocalcin, cbfa1, osterix and
      dlx5). Results obtained with the combined treatment yielded more activity than
      just the BMP-2 treatment or stretching alone. These results reveal that specific
      levels of static stretching force increase cell proliferation and effectively
      stimulate the osteoblast differentiation of C2C12 cells in conjunction with BMP-2
      stimulation, thus indicating a synergistic interaction between mechanical strain
      and cytokine signaling.

PMID- 19766221
TI  - Biomechanical and histological characteristics of passive esophagus: experimental
      investigation and comparative constitutive modeling.
AB  - Information on the passive biomechanical properties of two-layered esophagus is
      still limited, although this would enhance our understanding of its
      physiology/pathophysiology and help to address problems in surgery, medical
      device applications, and for the optimal design of prostheses. In this study,
      rabbit esophagi were excised and dissected into mucosa-submucosa and muscle
      layers that were submitted to histological quantification of elastin and collagen
      content and orientation, as well as to inflation-extension testing and
      geometrical analysis, i.e. delineation of the zero-stress state serving as a
      reference configuration for biomechanical analysis. The pressure-radius data of
      both layers displayed a monotonically rising slope with inflating pressure,
      unlike the sigma shape characterizing elastin-rich tissues, for which biphasic
      constitutive models were initially postulated. Three phenomenological expressions
      of strain-energy function (SEF), commonly appearing in soft-tissue biomechanics
      literature, were used in an attempt to model the pseudoelastic response of
      esophageal tissue, namely the exponential Fung-type SEF, and the combined neo
      Hookean (isotropic) or quadratic (anisotropic) and exponential Fung-type SEF.
      Accurate fits were attained for the pressure-radius-force data, spanning a wide
      range of longitudinal stretch ratios, when using the exponential form; the
      biphasic SEFs failed to generate improved fits, being also over-parameterized.
      According to the calculated material parameters, mucosa-submucosa was stiffer
      than muscle in both directions, justified by our histological observation of
      increased collagen content in that layer, and tissue was stiffer longitudinally,
      substantiated by the increased elastin and collagen contents and their
      preferential alignment towards that direction. Our results demonstrate that the
      passive response of esophagus is best modeled with an exponential Fung-type SEF.

PMID- 19766222
TI  - Regional stiffening of the mitral valve anterior leaflet in the beating ovine
      heart.
AB  - Left atrial muscle extends into the proximal third of the mitral valve (MV)
      anterior leaflet and transient tensing of this muscle has been proposed as a
      mechanism aiding valve closure. If such tensing occurs, regional stiffness in the
      proximal anterior mitral leaflet will be greater during isovolumic contraction
      (IVC) than isovolumic relaxation (IVR) and this regional stiffness difference
      will be selectively abolished by beta-receptor blockade. We tested this
      hypothesis in the beating ovine heart. Radiopaque markers were sewn around the MV
      annulus and on the anterior MV leaflet in 10 sheep hearts. Four-dimensional
      marker coordinates were obtained from biplane videofluoroscopy before (CRTL) and
      after administration of esmolol (ESML). Heterogeneous finite element models of
      each anterior leaflet were developed using marker coordinates over matched
      pressures during IVC and IVR for CRTL and ESML. Leaflet displacements were
      simulated using measured left ventricular and atrial pressures and a response
      function was computed as the difference between simulated and measured
      displacements. Circumferential and radial elastic moduli for ANNULAR, BELLY and
      EDGE leaflet regions were iteratively varied until the response function reached
      a minimum. The stiffness values at this minimum were interpreted as the in vivo
      regional material properties of the anterior leaflet. For all regions and all
      CTRL beats IVC stiffness was 40-58% greater than IVR stiffness. ESML reduced
      ANNULAR IVC stiffness to ANNULAR IVR stiffness values. These results strongly
      implicate transient tensing of leaflet atrial muscle during IVC as the basis of
      the ANNULAR IVC-IVR stiffness difference.

PMID- 19766223
TI  - Novel approach for a precise determination of short-time intervals in ankle
      sprain experiments.
AB  - The etiology of ankle sprain injury is still under debate. Therefore, diagnoses
      of ankle inversion experiments play an important role. Recent studies stress the
      importance of exact time measurements due to the short inversion period of around
      70ms. This paper presents a novel approach using the vertical ground reaction
      force (vGRF) to determine the short-time intervals in ankle sprain experiments,
      which are present in the form of short periods from the beginning of the movement
      to its end and short latencies to following signals, e.g. EMG onset of peroneal
      muscles. We compare our method to electrogoniometry at the ankle which is
      considered as the gold standard. During the inversion movement the kinematic
      action at the ankle can be measured with electrogoniometry, whereas the vGRF
      quantifies the vertical dynamic reaction of the tested subject entirely. We
      observe a difference of DeltaT(f,0-->g,0)=10+/-0.5ms between the first observable
      vGRF response and the first observable electrogoniometer response following
      platform release. The end of the ankle inversion measured with electrogoniometry
      is DeltaT(f,1-->g,1)=3+/-0.5ms later than the maximal vGRF peak. The potential
      supplementary (mechanical) information of this novel approach compared to
      electrogoniometry and its ease of use, may be not only interesting for
      researchers when studying ankle sprain simulations but also for clinicians when
      testing functional ankle stability.

PMID- 19766224
TI  - Automated image registration for assessing three-dimensional alignment of entire
      lower extremity and implant position using bi-plane radiography.
AB  - An automated image-matching technique is presented to assess alignment of the
      entire lower extremity for normal and implanted knees and the positioning of
      implants with respect to bone. Sawbone femur and tibia and femoral and tibial
      components of a total knee arthroplasty system were used. Three spherical markers
      were attached to each sawbone and each component to define the local coordinate
      system. Outlines of the three-dimensional (3D) bone models and component computer
      aided design (CAD) models were projected onto extracted contours of the femur,
      tibia, and implants in frontal and oblique X-ray images. Three-dimensional
      position of each model was recovered by minimizing the difference between the
      projected outline and the contour. Median values of the absolute error in
      estimating relative positions were within 0.5mm and 0.6 degrees for the femur
      with respect to the tibia, 0.5mm and 0.5 degrees for the femoral component with
      respect to the tibial component, 0.6mm and 0.6 degrees for the femoral component
      with respect to the femur, and 0.5mm and 0.4 degrees for the tibial component
      with respect to the tibia, indicating significant improvements when compared to
      manually obtained results.

PMID- 19766225
TI  - Patient-specific analyses of deep tissue loads post transtibial amputation in
      residual limbs of multiple prosthetic users.
AB  - Active transtibial amputation (TTA) patients are at risk for developing pressure
      ulcers (PU) and deep tissue injury (DTI) while using their prosthesis. It is
      therefore important to obtain knowledge of the mechanical state in the internal
      soft tissues of the residuum, as well as knowledge of the mechanical state upon
      its surface. Our aim was to apply patient-specific MRI-based non-linear finite
      element (FE) models to quantify internal strains in TTA prosthetic users (n=5)
      during load-bearing. By further employing a strain injury threshold for skeletal
      muscle, we identified patients susceptible to DTI. The geometrical
      characteristics of the residuum of the TTA participants varied substantially
      between patients, e.g. the residuum lengths were 7.6, 8.1, 9.2, 11.5 and 13.3cm.
      We generally found that internal strains were higher in the bone proximity than
      in the muscle flap periphery. The highest strains, which in some patients
      exceeded 50% (engineering strain) for compressive, tensile and shear strains,
      were found in the shortest residual limbs, i.e. the 7.6 and 8.1cm-long limbs.
      Correspondingly, the lowest strains were found in the 13.3cm-long residuum, which
      had the bulkiest muscle flap. Yet, even in the case of a long residuum, about a
      third of the soft tissue volume at the distal tibial proximity area was occupied
      by large (>5%) internal compressive, tensile and shear strains. For both patients
      with shorter residual limbs, the internal principal compressive strains above 5%
      occupied almost the entire distal tibial proximity area. For a patient whose
      distal tibial end was flat (non-beveled), internal strains were more uniformly
      distributed, compared to the strain distributions in the other models, where
      focal elevated strains accumulated in the bone proximity. We found no muscle
      strains above the immediate injury threshold, indicating that all patients were
      not at immediate risk for DTI. Two patients whose residuum fat padding was
      minimal to none, were the only ones identified as theoretically prone to DTI at
      long (>3h) continuous weight-bearing periods. We conclude that there is a wide
      variability in internal mechanical conditions between residual limbs across
      subjects, which necessitates patient-specific quantitative analyses of internal
      mechanical states in TTA patients, to assess the mechanical performance of the
      reconstructed limb and in particular, the individual risk for deep PU or DTI.

PMID- 19766226
TI  - Tensile and compressive properties of fresh human carotid atherosclerotic
      plaques.
AB  - Accurate characterisation of the mechanical properties of human atherosclerotic
      plaque is important for our understanding of the role of vascular mechanics in
      the development and treatment of atherosclerosis. The majority of previous
      studies investigating the mechanical properties of human plaque are based on
      tests of plaque tissue removed following autopsy. This study aims to characterise
      the mechanical behaviour of fresh human carotid plaques removed during
      endarterectomy and tested within 2h. A total of 50 radial compressive and 17
      circumferential tensile uniaxial tests were performed on samples taken from 14
      carotid plaques. The clinical classification of each plaque, as determined by
      duplex ultrasound is also reported. Plaques were classified as calcified, mixed
      or echolucent. Experimental data indicated that plaques were highly
      inhomogeneous; with variations seen in the mechanical properties of plaque
      obtained from individual donors and between donors. The mean behaviour of samples
      for each classification indicated that calcified plaques had the stiffest
      response, while echolucent plaques were the least stiff. Results also indicated
      that there may be a difference in behaviour of samples taken from different
      anatomical locations (common, internal and external carotid), however the large
      variability indicates that more testing is needed to reach significant
      conclusions. This work represents a step towards a better understanding of the in
      vivo mechanical behaviour of human atherosclerotic plaque.

PMID- 19766227
TI  - Colloidal transport of uranium in soil: Size fractionation and characterization
      by field-flow fractionation-multi-detection.
AB  - The aim of this study was to characterize colloids associated with uranium by
      using an on-line fractionation/multi-detection technique based on asymmetrical
      flow field-flow fractionation (As-Fl-FFF) hyphenated with UV detector, multi
      angle laser light scattering (MALLS) and inductively coupling plasma-mass
      spectrometry (ICP-MS). Moreover, thanks to the As-Fl-FFF, the different colloidal
      fractions were collected and characterized by a total organic carbon analyzer
      (TOC). Thus it is possible to determine the nature (organic or inorganic
      colloids), molar mass, size (gyration and hydrodynamic radii) and quantitative
      uranium distribution over the whole colloidal phase. In the case of the site
      studied, two populations are highlighted. The first population corresponds to
      humic-like substances with a molar mass of (1500+/-300)gmol(-1) and a
      hydrodynamic diameter of (2.0+/-0.2)nm. The second one has been identified as a
      mix of carbonated nanoparticles or clays with organic particles (aggregates
      and/or coating of the inorganic particles) with a size range hydrodynamic
      diameter between 30 and 450nm. Each population is implied in the colloidal
      transport of uranium: maximum 1% of the uranium content in soil leachate is
      transported by the colloids in the site studied, according to the depth in the
      soil. Indeed, humic substances are the main responsible of this transport in sub
      surface conditions whereas nanoparticles drive the phenomenon in depth
      conditions.

PMID- 19766228
TI  - Extraction of organic compounds with room temperature ionic liquids.
AB  - Room temperature ionic liquids are novel solvents with a rather specific blend of
      physical and solution properties that makes them of interest for applications in
      separation science. They are good solvents for a wide range of compounds in which
      they behave as polar solvents. Their physical properties of note that distinguish
      them from conventional organic solvents are a negligible vapor pressure, high
      thermal stability, and relatively high viscosity. They can form biphasic systems
      with water or low polarity organic solvents and gases suitable for use in liquid
      liquid and gas-liquid partition systems. An analysis of partition coefficients
      for varied compounds in these systems allows characterization of solvent
      selectivity using the solvation parameter model, which together with
      spectroscopic studies of solvent effects on probe substances, results in a
      detailed picture of solvent behavior. These studies indicate that the solution
      properties of ionic liquids are similar to those of polar organic solvents.
      Practical applications of ionic liquids in sample preparation include extractive
      distillation, aqueous biphasic systems, liquid-liquid extraction, liquid-phase
      microextraction, supported liquid membrane extraction, matrix solvents for
      headspace analysis, and micellar extraction. The specific advantages and
      limitations of ionic liquids in these studies is discussed with a view to
      defining future uses and the need not to neglect the identification of new room
      temperature ionic liquids with physical and solution properties tailored to the
      needs of specific sample preparation techniques. The defining feature of the
      special nature of ionic liquids is not their solution or physical properties
      viewed separately but their unique combinations when taken together compared with
      traditional organic solvents.

PMID- 19766229
TI  - Separation of positional isomers of mono-poly(ethylene glycol)-modified
      octreotides by reversed-phase high-performance liquid chromatography.
AB  - The purpose of this study was to develop a reversed-phase high-performance liquid
      chromatographic method (RP-HPLC) for separating each positional isomer from low-
      to high-molecular-weight mono-PEGylated octreotides prepared by polyethylene
      glycol (PEG) derivatives with various molecular weights (2, 5, or 20kDa). In the
      gradient elution using acetonitrile and 10mM phosphate buffer at pH 7.0 on a
      Phenomenex Gemini C-18 column (250mmx4.6mm id, 5microm), each positional isomer
      of the mono-PEGylated octreotides was completely resolved with good resolution
      (PEG-2K: 7.6, PEG-5K: 6.6, and PEG-20K: 3.1). The optimal RP-HPLC condition also
      resolved the degradation products of mono-PEG-octreotide isomers in thermal
      stability studies at 55 degrees C and enzymatic stability studies with trypsin.
      In conclusion, the developed RP-HPLC method will be valuable for studying the
      effect of PEGylation site and the attached PEG size on the physicochemical and
      pharmacological properties of PEGylated octreotides.

PMID- 19766230
TI  - Hybrid organic-inorganic silica monolith with hydrophobic/strong cation-exchange
      functional groups as a sorbent for micro-solid phase extraction.
AB  - A hybrid organic-inorganic silica monolith with hydrophobic and strong cation
      exchange functional groups was prepared and used as a sorbent for micro-solid
      phase extraction (micro-SPE). The hybrid silica monolith functionalized with
      octyl and thiol groups was conveniently synthesized by hydrolysis and
      polycondensation of a mixture of tetraethoxysilane (TEOS), n-octyltriethoxysilane
      (C8-TEOS) and 3-mercaptopropyltrimethoxysilane (MPTMS) via a two-step catalytic
      sol-gel process. Due to the favorable chemical reactivity of mercapto pendant
      moieties, the obtained hybrid monolith was oxidized using hydrogen peroxide (30%,
      w/w) to yield sulfonic acid groups, which provided strong cation-exchange sites.
      The obtained hybrid monolith was characterized by diffused infrared spectroscopy,
      elemental analysis, scanning electron microscopy and mercury intrusion
      porosimetry. The results show that the resulting monolith contains much higher
      carbon (31.6%) and sulfur (4.8%) contents than traditionally bonded silica
      materials. The extraction performance of the hybrid monolith was evaluated using
      sulfonamides as testing analytes by micro-SPE on-line coupled to HPLC. The
      results show that the hybrid monolith with hydrophobic and strong cation-exchange
      functional groups exhibits high extraction efficiency towards the testing
      analytes. The column-to-column RSD values were 1.3-9.8% for the extraction of SAs
      investigated. The extraction performance of the hybrid silica monolith remained
      practically unchanged after treated with acid (pH 1.0) and basic solutions (pH
      10.5). Finally, the application of the hybrid monolith was demonstrated by micro
      SPE of sulfonamide residues from milk followed by HPLC-UV analysis. The limits of
      detection (S/N=3) for eight SAs were found to be 1.0-3.0ng/mL in milk. The
      recoveries of eight SAs spiked in milk sample ranged from 80.2% to 115.6%, with
      relative standard deviations less than 11.8%.

PMID- 19766231
TI  - Hydrophilic hypercrosslinked polymeric sorbents for the solid-phase extraction of
      polar contaminants from water.
AB  - Three new hypercrosslinked polymers with hydrophilic character arising from
      hydroxyl moieties in their skeletons have been prepared in microsphere format and
      applied to the off-line solid-phase extraction (SPE) of polar compounds from
      water samples. For sample volumes of 1000 ml, the recoveries of various polar
      pesticides, such as oxamyl, methomyl, selected phenolic compounds, as well as
      some pharmaceuticals, were close to 90%. The HXLPP-polar polymer with the best
      performance characteristics was applied to real samples. Its performance was also
      compared to commercially available sorbents, such as LiChrolut EN (hydrophobic,
      hypercrosslinked), Oasis HLB (hydrophilic, macroporous) and Isolute ENV+
      (hydrophilic, hypercrosslinked); the new sorbent out-performed the commercially
      available sorbents. The polymer was applied successfully in off-line SPE of river
      water samples followed by liquid chromatography and ultraviolet detection,
      providing a good linear range and detection limits of 0.2 microg l(-1) for the
      majority of the compounds, with the exception of oxamyl, methomyl, guaiacol and
      salicylic acid where the detection limit was 0.5 microg l(-1).

PMID- 19766232
TI  - Synthesis of large pore-diameter SBA-15 mesostructured spherical silica and its
      application in ultra-high-performance liquid chromatography.
AB  - A modified synthesis approach for spherical large pore-diameter SBA-15 mesoporous
      silica (SLP-SBA-15) with particle size range of 0.5-1microm was being reported.
      It was worth mentioning that in this improved methodology, the use of
      cetyltrimethylammonium bromide (CTAB) as co-template significantly reduced the
      self-assembly time from 24h to 45min. Moreover, under reflux condition, the
      reaction time could be further shortened by reducing the aging time from 48h to
      6h. The resultant SLP-SBA-15 was thereafter successfully functionalized and
      packed into an ultra-high-performance liquid chromatography (UHPLC) column for
      the separation of aromatic compounds. A variety of characterizations demonstrated
      that the silica products exhibited a well-ordered 2d hexagonal mesostructure with
      well-formed spherical morphology. pore-diameter can be enlarged up to 8.2nm
      without affecting the structural order. The SLP-SBA-15 samples showed excellent
      thermal and hydrothermal stabilities. The octadecyltriethoxysilane functionalized
      SLP-SBA-15 (SLP-C18-SBA-15) was demonstrated to be an effective stationary phase
      in UHPLC application because the column exhibited significantly reduced column
      pressure (2800psi) at a flow rate of 0.4ml/min. Accordingly, it would afford
      greater flexibility for tuning of the flow rate to meet the fast separation
      requirement.

PMID- 19766233
TI  - Determination of descriptors for semivolatile organosilicon compounds by gas
      chromatography and non-aqueous liquid-liquid partition.
AB  - The measurement of retention factors by gas chromatography on up to 15 stationary
      phases at several temperatures in the range 60-240 degrees C for each stationary
      phase and liquid-liquid partition coefficients in three biphasic organic solvent
      systems (n-hexane-acetonitrile, n-heptane-N,N-dimethylformamide, and n-heptane
      2,2,2-trifluoroethanol) were used to calculate solute descriptors for 28
      semivolatile linear and cyclic organosilicon compounds for use in the solvation
      parameter model. Regression analysis for oligomeric compounds allowed the
      descriptor values for the dimethylsiloxane, diethylsiloxane, methylvinylsiloxane,
      and methylhydrosiloxane monomer groups to be estimated. These monomer groups
      contribute significantly to the hydrogen-bond basicity (B descriptor) and cavity
      formation and dispersion interactions (L and V descriptors) of oligomeric
      organosilicon compounds, are non-hydrogen-bond acidic (A descriptor=0), are
      slightly less dipolar/polarizable than an n-alkane (S descriptors are negative
      and close to zero), and bind electron lone pairs more tightly than an n-alkane (E
      descriptor is small and negative). The semivolatile organosilicon compounds with
      polar functional groups in their side chain demonstrate a much wider range of
      selective intermolecular interactions than alkylsiloxanes and have solvation
      properties closer to those of polar organic compounds.

PMID- 19766234
TI  - Dispersive liquid-liquid microextraction method based on solidification of
      floating organic drop for extraction of organochlorine pesticides in water
      samples.
AB  - A new simple and rapid dispersive liquid-liquid microextraction method has been
      developed for the extraction and analysis of organochlorine pesticides (OCPs) in
      water samples. The method is based on the solidification of a floating organic
      drop (DLLME-SFO) and is combined with gas chromatography/electron capture
      detection (GC/ECD). Very little solvent is required in this method. The disperser
      solvent (200microL acetonitrile) containing 10microL hexadecane (HEX) is rapidly
      injected by a syringe into the 5.0mL water sample. After centrifugation, the fine
      HEX droplets (6+/-0.5microL) float at the top of the screw-cap test tube. The
      test tube is then cooled in an ice bath. After 5min, the HEX solvent solidifies
      and is then transferred into a conical vial, where it melts quickly at room
      temperature, and 1microL of it is injected into a gas chromatograph for analysis.
      Under optimum conditions, the enrichment factors and extraction recoveries are
      high and range between 37-872 and 82.9-102.5%, respectively. The linear range is
      wide (0.025-20microgL(-1)), and the limits of detection are between 0.011 and
      0.11microgL(-1) for most of the analytes. The relative standard deviation (RSD)
      for 1microgL(-1) of OCPs in water was in the range of 5.8-8.8%. The performance
      of the method was gauged by analyzing samples of lake and tap water.

PMID- 19766235
TI  - Adverse ventricular remodeling and exacerbated NOS uncoupling from pressure
      overload in mice lacking the beta3-adrenoreceptor.
AB  - Stimulation of the beta-adrenergic system is important in the pathological
      response to sustained cardiac stress, forming the rationale for the use of beta
      blockers in heart failure. The beta3-adrenoreceptor (AR) is thought to couple to
      the inhibitory G-protein, G(i), with downstream signaling through nitric oxide,
      although its role in the heart remains controversial. In this study, we tested
      whether lack of beta3-AR influences the myocardial response to pressure-overload.
      Baseline echocardiography in mice lacking beta3-AR (beta3(-/-)) compared to wild
      type (WT) showed mild LV hypertrophy at 8 weeks that worsened as they aged.
      beta3(-/-) mice had much greater mortality after transverse aortic constriction
      (TAC) than WT controls. By 3 weeks of TAC, systolic function was worse. After 9
      weeks of TAC, beta3(-/-) mice also had greater LV dilation, myocyte hypertrophy
      and enhanced fibrosis. NOS activity declined in beta3(-/-)TAC hearts after 9
      weeks, and total and NOS-dependent superoxide rose, indicating heightened
      oxidative stress and NOS uncoupling. The level of eNOS phosphorylation in beta3(
      /-)TAC hearts was diminished, and nNOS and iNOS expression levels were increased.
      GTP cyclohydrolase-1 expression was reduced, although total BH4 levels were not
      depleted. 3 weeks of BH4 treatment rescued beta3(-/-) mice from worsened
      remodeling after TAC, and lowered NOS-dependent superoxide. Thus, lack of beta3
      AR signaling exacerbates cardiac pressure-overload induced remodeling and
      enhances NOS uncoupling and consequent oxidant stress, all of which can be
      rescued with exogenous BH4. These data suggest a cardioprotective role for the
      beta3-AR in modulating oxidative stress and adverse remodeling in the failing
      heart.

PMID- 19766236
TI  - Allele specific analysis of the ADRBK2 gene in lymphoblastoid cells from bipolar
      disorder patients.
AB  - G-protein coupled receptor kinase-3 (GRK3), translated from the gene, ADRBK2 has
      been implicated as a candidate molecule for bipolar disorder through multiple,
      converging lines of evidence. In some individuals, the ADRBK2 gene harbors the A
      haplotype, a collection of single nucleotide polymorphisms (SNPs) previously
      associated with an increased risk for bipolar disorder. Because the A-haplotype
      encompasses the ADRBK2 promoter, we hypothesized that it may alter the regulation
      of gene expression. Using histone H3 acetylation to infer promoter activity in
      lymphoblastoid cells from patients with bipolar disorder, we examined the A
      haplotype within its genomic context and determined that at least four of its
      SNPs are present in transcriptionally active portions of the promoter. However,
      using chromatin immunoprecipitation followed by allele-specific PCR in samples
      heterozygous for the A-haplotype, we found no evidence of altered levels of
      acetylated histone H3 at the affected allele compared to the common allele.
      Similarly, using a transcribed SNP to discriminate expressed ADRBK2 mRNA strands
      by allele of origin; we found that the A-haplotype did not confer an allelic
      expression imbalance. Our data suggest that while the A-haplotype is situated in
      active regulatory sequence, the risk-associated SNPs do not appear to affect
      ADRBK2 gene regulation at the level of histone H3 acetylation nor do they confer
      measurable changes in transcription in lymphoblastoid cells. However, tissue
      specific mechanisms by which the A-haplotype could affect ADRBK2 in the central
      nervous system cannot be excluded.

PMID- 19766237
TI  - Hydroxyethyl starch 130/0.4 inhibits production of plasma proinflammatory
      cytokines and attenuates nuclear factor-kappaB activation and Toll-like receptors
      expression in monocytes during sepsis.
AB  - BACKGROUND: Hydroxyethyl starch (HES) is one of the most frequently used plasma
      substitutes, and could modulate inflammatory response in sepsis. Our aim of this
      study was to investigate the mechanism of the effect of HES 130/0.4 by studying
      plasma levels of inflammatory cytokines, nuclear factor-kappaB (NF-kappaB)
      activation, and Toll-like receptors (TLRs) expression in peripheral monocytes
      during polymicrobial sepsis. MATERIALS AND METHODS: Rats with sepsis induced by
      cecal ligation and puncture (CLP) were treated with HES130/0.4 (7.5, 15, or 30
      mL/kg, intravenously); then, rat plasma and monocytes were isolated from blood 5
      h later. The plasma level of cytokines (tumor necrosis factor [TNF]-alpha and
      interleukin [IL]-6), NF-kappaB activity, and mRNA and protein levels of TLRs
      (TLR2 and TLR4) in peripheral blood monocytes were determined by enzyme-linked
      immunosorbent assay, electrophoretic mobility shift assay, reverse transcription
      polymerase chain reaction, and Western blotting, respectively. RESULTS:
      HES130/0.4 dose-dependently reduced the plasma level of TNF-alpha and IL-6 in
      rats with sepsis. HES130/0.4 also significantly inhibited NF-kappaB activation,
      and TLRs mRNA and protein levels in peripheral monocytes. CONCLUSION: During
      sepsis, HES130/0.4 can down-regulate the inflammatory response, possibly through
      inhibition of the TLRs/NF-kappaB signaling pathway, and could be one more
      appropriate plasma substitute in sepsis.

PMID- 19766238
TI  - The impact of lidocaine on flap survival following reperfusion injury.
AB  - BACKGROUND: Inflammatory events triggered by the mediators released from free
      oxygen radicals and infiltrated leukocytes play a direct role in formation of the
      ischemia-reperfusion (IR) injury. The aim of this study was to investigate the
      impact of lidocaine on IR injury due to its anti-inflammatory properties.
      MATERIALS AND METHODS: Following delivery of lidocaine to the ischemic flaps in
      two different doses prior to the reperfusion, flap survival, malondialdehyde
      (MDA) level, myeloperoxidase (MPO) level, neutrophil count, and measurement of
      vascular diameters were studied. Twelve hours after reperfusion, tissue specimens
      were collected for measurement of MDA level, MPO level, neutrophil count, and
      vascular diameters. Flap survival was evaluated on the fifth day. RESULTS: Flap
      survival rate was 15.54% +/- 8.23% in the control group, whereas the groups
      treated wtih lidocaine showed remarkable elevations in survival rates as follows:
      70.83% +/- 33.53% and 67.42% +/- 30.81%, respectively. MDA levels in sham and
      lidocaine treatment groups were significantly lower than those observed in
      control group. CONCLUSION: Lidocaine inhibited the increase in MDA level
      associated with IR injury while showing no influence over increases in number of
      neutrophils and tissue MPO level, and it elevated the flap survival rate.

PMID- 19766239
TI  - Fumarate in the preservation solution aggravates chronic allograft nephropathy.
AB  - Data on a protective role of fumarate in acute ischemia of the rat heart led to
      the obvious hypothesis that addition of fumarate to the preservation solution for
      kidney transplantation may have beneficial value. This study was designed to test
      this hypothesis. Kidneys of Lewis or Fischer 344 rats were flushed with
      University of Wisconsin (UW) solution or UW solution containing 5 mM fumarate.
      Grafts were immediately transplanted to Lewis recipients or stored at 4  degrees
      C for 5 h before transplantation. Renal function was assessed on d 10 and monthly
      for 6 mo. One group of isografts was removed on d 10 post-transplantation, the
      other groups of isografts and allografts after 6 mo. We detected a modest
      protective effect regarding proteinuria 10 d after isogeneic transplantation, and
      exclude the possibility that fumarate exerts acute nephrotoxicity. Surprisingly,
      fumarate strongly promoted intimal hyperplasia of allograft arteries, thickening
      of the arterial media of isografts and allografts, tubulo-interstitial allograft
      damage, and allograft infiltration by macrophages on the long run. To date, we do
      not know the mechanism resulting in fumarate-induced chronic graft damage. We
      suggest, however, that addition of fumarate to the conservation fluid does not
      improve graft outcome.

PMID- 19766240
TI  - Do ameroid constrictors reliably occlude porcine coronary arteries?

PMID- 19766241
TI  - Management and outcomes for children with pyloric stenosis stratified by hospital
      type.
AB  - BACKGROUND: Access to health care has been a source of controversy and public
      attention in health policy. The issues of access to and utilization of the
      healthcare system by infants and children is less well documented. Moreover, the
      impact on outcomes of race, ethnicity, and economic status in infants is vaguely
      addressed. METHODS: We performed a retrospective analysis of children who had
      undergone pyloromyotomy from July 31, 1998 to July 31, 2008 at our public
      hospital and university teaching hospital. Data abstracted included gestational
      age at delivery, birth weight, gender, race, insurance status, age at
      presentation, symptom duration, preoperative ultrasound (US), operative date,
      laboratory evaluations, as well as preoperative, postoperative, and total length
      of stay (LOS). RESULTS: The mean total preoperative LOS was twice as long at our
      public hospital than our private hospital (1.78 d versus 0.85 d, P=0.003).
      Similarly, the mean total length of stay was 0.87 d longer at our public hospital
      (3.87 d versus 3 d), which trended toward significance (P=0.06). Significantly,
      72% (27/33) patients at the private hospital had their US either as an out
      patient or on the day of admission, while only 58% (28/48) had an US performed as
      expeditiously at the public hospital (P=0.03, chi(2) analysis). CONCLUSIONS: Care
      at our public hospital leads to delayed diagnosis and treatment, resulting in
      longer preoperative and total LOS in infants with pyloric stenosis, most likely
      related to the timing of the preoperative US. Efforts should be made to encourage
      patients to use the outpatient clinic facilities for their ill infants, or for
      physicians at public hospitals to expedite the US process once the diagnosis of
      pyloric stenosis is entertained.

PMID- 19766242
TI  - Academic needs in developing countries: a survey of the West African College of
      Surgeons.
AB  - BACKGROUND: The inaugural Fundamentals of Surgical Research Course was held in
      Sierra Leone in conjunction with the West African College of Surgeons (WACS). We
      subsequently performed a formal assessment of the academic needs of West African
      surgeons to plan for future courses, and hypothesized that they would differ from
      the goals of the U.S. course. METHODS: A survey was distributed via email to
      members of the WACS and returned by the same mechanism. It consisted of 6
      questions addressing specific elements of the inaugural course, and potential new
      topics for future courses. RESULTS: Over half (53%, 25/47) of the respondents had
      not attended the inaugural course, while 85% (40/47) planned on attending the
      next course. Respondents identified least useful topics from the initial course
      as "Molecular Biology: Tools of the Trade" (45%, 21/47) and "Getting Promoted"
      (23%, 11/47). The least popular potential new topics were "Use and Abuse of
      Administrative Databases" (9%, 4/47), "Animal Models" (21%, 10/47), and "Genomics
      and Proteomics" (21%, 10/47). CONCLUSIONS: The self-reported academic needs of
      West African surgeons are oriented toward clinical research. Basic and
      translational research topics are of secondary interest to the majority of
      respondents. Future courses in this region must address specific local needs.

PMID- 19766243
TI  - Right ventricular failure resulting from pressure overload: role of intra-aortic
      balloon counterpulsation and vasopressor therapy.
AB  - BACKGROUND: Augmentation of coronary perfusion may improve right ventricular (RV)
      failure following acute increases of RV afterload. We investigated whether intra
      aortic balloon counterpulsation (IABP) can improve cardiac function by enhancing
      myocardial perfusion and reversing compromised biventricular interactions using a
      model of acute pressure overload. MATERIALS AND METHODS: In 10 anesthetized pigs,
      RV failure was induced by pulmonary artery constriction and systemic hypertension
      strategies with IABP, phenylephrine (PE), or the combination of both were tested.
      Systemic and ventricular hemodynamics [cardiac index(CI), ventricular pressures,
      coronary driving pressures (CDP)] were measured and echocardiography was used to
      assess tricuspid valve regurgitation, septal positioning (eccentricity index
      (ECI)), and changes in ventricular and septal dimensions and function [myocardial
      performance index (MPI), peak longitudinal strain]. RESULTS: Pulmonary artery
      constriction resulted in doubling of RV systolic pressure (54 +/- 4mm Hg), RV
      distension, severe TR (4+) with decreased RV function (strain: -33%; MPI: +56%),
      septal flattening (Wt%: -35%) and leftward septal shift (ECI:1.36), resulting in
      global hemodynamic deterioration (CI: -51%; SvO(2): -26%), and impaired CDP (
      30%; P<0.05). IABP support alone failed to improve RV function despite higher CDP
      (+33%; P<0.05). Systemic hypertension by PE improved CDP (+70%), RV function
      (strain: +22%; MPI: -21%), septal positioning (ECI:1.12) and minimized TR, but LV
      dysfunction (strain: -25%; MPI: +31%) occurred after LV afterloading (P<0.05).
      With IABP, less PE (-41%) was needed to maintain hypertension and CDP was further
      augmented (+25%). IABP resulted in LV unloading and restored LV function, and
      increased CI (+46%) and SvO(2) (+29%; P<0.05). CONCLUSIONS: IABP with minimal
      vasopressors augments myocardial perfusion pressure and optimizes RV function
      after pressure-induced failure.

PMID- 19766244
TI  - Monotherapy with a tumor-targeting mutant of S. typhimurium inhibits liver
      metastasis in a mouse model of pancreatic cancer.
AB  - Cancer of the exocrine pancreas is the fourth leading cause of cancer deaths in
      the United States. Currently, surgical resection is the only hope for cure. The
      majority of patients present with locally-advanced or metastatic disease. The
      most common site for distant metastasis is the liver. We report here a modified
      auxotrophic strain of S. typhimurium that can target and inhibit the growth of
      liver metastasis in a mouse model of pancreatic cancer. This strain of S.
      typhimurium is auxotrophic (leucine-arginine dependent) but apparently receives
      sufficient nutritional support from tumor tissue. To increase tumor targeting
      ability and tumor killing efficacy, this strain was further modified by re
      isolation from a tumor growing in a nude mouse and termed A1-R. In the present
      study, we demonstrate the efficacy of locally- as well as systemically
      administered A1-R on liver metastasis of pancreatic cancer. Mice treated with A1
      R given locally via intrasplenic injection or systemically via tail vein
      injection had a much lower hepatic and splenic tumor burden compared with control
      mice. Systemic treatment with intravenous A1-R also increased survival time. All
      results were statistically significant. This study suggests the clinical
      potential of bacterial treatment of a critical metastatic target of pancreatic
      cancer.

PMID- 19766245
TI  - The controlled release of basic fibroblast growth factor promotes a rapid healing
      of pancreaticojejunal anastomosis with potent angiogenesis and accelerates
      apoptosis in granulation tissue.
AB  - BACKGROUND: Our previous study demonstrated that bFGF-GH promoted healing of the
      pancreaticojejunostomy (PJ) in an animal model. We examined the healing process
      in detail to investigate the significance of treatment with basic fibroblast
      growth factor (bFGF) incorporated in gelatin hydrogel (GH) microspheres for
      anastomotic healing. MATERIALS AND METHODS: The optimal dose of bFGF was
      determined by administering bFGF concentrations of 1, 10, and 100 MUg in six
      beagle dogs and assessing the results on d 7. Next, 28 dogs received a jejunal
      subserosal injection of 10 MUg bFGF-GH or GH alone. The healing process was
      sequentially analyzed on d 4, 7, 21, and 28. The following types of assessment
      were performed: breaking strength test, pathologic examination, and calculations
      of collagen content, terminal deoxynucleotidyl transferase-mediated dUTP nick-end
      labeling (TUNEL) index, and microvessel density (MVD). RESULTS: The
      administration of a bFGF dose of more than 10 MUg induced a significantly higher
      breaking strength and more abundant granulation tissues. Histologic observations
      of the bFGF-GH group on d 7 and the GH-alone group on d 21 revealed abundant
      granulation tissue with migrating fibroblasts, inflammatory cells, and
      capillaries. Marked neovascularization and dense collagen deposition were
      detected in both groups on d 28. The collagen content and breaking strength did
      not significantly differ between both groups on d 28. A significantly higher
      TUNEL index and a rapid decline in the number of vimentin-positive cells were
      detected in the bFGF-GH group from d 21 onward. The MVD in the bFGF-GH group was
      significantly higher from d 7 onward CONCLUSIONS: Basic FGF-GH administration can
      promote the rapid completion of PJ anastomosis and may help improve the quality
      of the healing of granulation tissue by conferring potent angiogenesis and
      accelerating apoptosis.

PMID- 19766246
TI  - Gabexate mesilate inhibits the expression of HMGB1 in lipopolysaccharide-induced
      acute lung injury.
AB  - High mobility group box 1 (HMGB1) is an important late mediator of acute lung
      injury. Gabexate mesilate (GM) is a synthetic protease inhibitor with some anti
      inflammatory action. We aimed to evaluate the effect of GM on HMGB1 in
      lipopolysaccharide (LPS)-induced lung injury in rats. Prior to the injection of
      LPS to induce lung injury, rats were administered saline or GM. Injury to the
      lung and expression of HMGB1, plasminogen activator inhibitor-1 (PAI-1), and
      protease-activated receptor-2 (PAR-2) were examined. In an accompanying in vitro
      study, we performed LPS stimulation under GM administration in a mouse macrophage
      cell line and measured the quantity of HMGB1 and cytokines in the supernatant,
      and cell signal in the cells. Histologic examination revealed that interstitial
      edema, leukocytic infiltration, and HMGB1 protein expression were markedly
      reduced in the GM+LPS group compared wih the LPS group. Furthermore, LPS-induced
      increases in PAI-1 and PAR-2 activity and in plasma HMGB1 concentrations were
      lower in the rats given both GM and LPS than in the rats given LPS alone. Release
      of HMGB1 and cytokines from the cell after the administration of LPS were
      decreased by GM. Phosphorylation of IkappaB was inhibited by GM. GM may have
      inhibited PAI-1 and PAR-2, thereby indirectly inhibiting HMGB1 and reducing
      tissue damage in the lung. This indicates that GM can inhibit lung injury induced
      by LPS in rats. GM is a candidate for use in novel strategies to prevent or
      minimize lung injury in sepsis.

PMID- 19766247
TI  - Platonin improves survival of skin allografts.
AB  - BACKGROUND: Platonin is an immunomodulator with NF-kappaB inhibitory activity. It
      not only inhibits interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)
      alpha production in sepsis, but also attenuates heatstroke reactions. In
      addition, platonin redirects differentiation of dendritic cells toward an
      intermediate stage of maturation. The study was designed to examine whether
      platonin can reduce acute graft rejection. MATERIALS AND METHODS: A C57BL/6 to
      BALB/c mice skin transplantation model was used. Platonin was given
      intraperitoneally to transplant recipients at various doses. Skin grafts were
      submitted to histologic analysis. NF-kappaB DNA binding activity and inducible
      nitric oxide synthase (iNOS) expression were determined in harvested draining
      lymph nodes. Leukocyte count, hepatic and renal functions were serially assessed.
      An array of serum cytokines was evaluated on d 1, 3, 5, and 7 after skin
      transplantation. RESULTS: Platonin resulted in significantly prolonged skin
      allograft survival in a dose- and time-dependent manner. Histologic changes in
      the skin allografts paralleled the gross appearance of rejection. Serum cytokine
      analysis shows that platonin significantly suppressed the production of the
      proinflammatory cytokines IL-6 and TNF-alpha. However, no significant changes
      occurred in the serum levels of Th1-type and Th2-type cytokines. NF-kappaB
      activity and iNOS expression were remarkably suppressed in draining lymph nodes.
      In terms of toxicity, there were no significant differences in body weight,
      leukocyte count, plasma alanine aminotransferase, or creatinine between the
      platonin-treated and control groups. CONCLUSION: Platonin effectively prolongs
      skin allograft survival without major toxicity.

PMID- 19766248
TI  - Intrafamilial clinical phenotypic heterogeneity with MAPT gene splice site
      IVS10+16C>T mutation.
AB  - Two families with frontotemporal dementia with parkinsonism linked to chromosome
      17 (FTDP-17) resulting from the microtubule associated protein tau (MAPT) gene
      IVS10+16C>T splice site mutation are reported, members of which showed variable
      clinical phenotypes at presentation. Possible explanations for the intra- and
      interfamilial clinical heterogeneity associated with this MAPT mutation are
      discussed.

PMID- 19766249
TI  - Hemibody mirror movements in hemiparkinsonism-hemiatrophy syndrome.
AB  - Hemiparkinsonism-hemiatrophy syndrome (HPHA) is a relatively rare cause of
      secondary parkinsonism. Mirror movements (MM) are associated with a variety of
      congenital and acquired conditions, including some forms of parkinsonism. This
      report describes a patient with the HPHA phenotype who exhibited MM, a feature
      that has not been previously reported in this syndrome. Surface electromyography
      (EMG) was used to illustrate the virtually simultaneous occurrence of voluntary
      and involuntary movements. Needle EMG was used to diagnose a spinal accessory
      neuropathy. Pathological mirroring or overflow movement of the orbicularis oculi
      muscle is also hypothesized. The clinical features are demonstrated on video.

PMID- 19766250
TI  - Changes in risk factors and preventive treatments by stroke subtypes over 20
      years: a population-based study.
AB  - In order to evaluate progress in preventive therapeutic strategies, and to
      identify potential targets for improvement, it is essential to assess changes in
      the risk factors and preventive treatment of stroke over time. All of the strokes
      occurring within the population of Dijon, France (150,000 inhabitants), were
      prospectively ascertained from 1985 to 2004. Changes in stroke risk factors and
      preventive medications were analyzed by stroke subtypes. We recorded 725 lacunar
      infarcts (LI), 497 cardioembolic (CE) strokes, 2054 ischemic stroke from atheroma
      of large arteries or from other and undetermined causes (OIS), and 341 primary
      cerebral haemorrhages (PCH). Over the 20years, the prevalence of
      hypercholesterolemia increased whatever the stroke subtype (p<0.01) whereas that
      of diabetes only rose in LI and OIS stroke. The proportion of stroke patients on
      antiplatelet agents increased overall (p<0.01) and the proportion of patients on
      anticoagulants rose in CE stroke (p=0.01) and PCH (p<0.01). The proportion of
      patients on antihypertensive treatment only increased in CE stroke (p=0.01). The
      risk factor profile and the preventive treatments in stroke patients showed
      divergent variations over the 20years, according to the stroke subtype
      considered. These modifications certainly reflect changes in the therapeutic
      strategies for the preventive management of the population at risk.

PMID- 19766252
TI  - Re: Adjuvant radiotherapy for pathological T3N0M0 prostate cancer significantly
      reduces risk of metastases and improves survival: long-term followup of a
      randomized clinical trial I. M. Thompson, C. M. Tangen, J. Paradelo, M. S. Lucia,
      G. Miller, D. Troyer, E. Messing, J. Forman, J. Chin, G. Swanson, E. Canby-Hagino
      and E. D. Crawford J Urol 2009; 181: 956-962.

PMID- 19766255
TI  - Re: Does previous extracorporeal shock wave lithotripsy affect the performance
      and outcome of percutaneous nephrolithotomy? E. Yuruk, A. Tefekli, E. Sari, M. A.
      Karadag, A. Tepeler, M. Binbay and A. Y. Muslumanoglu J Urol 2009; 181: 663-667.

PMID- 19766256
TI  - Benthic foraminifera from two coastal lakes of southern Latium (Italy).
      Preliminary evaluation of environmental quality.
AB  - Benthic foraminifera and sediment texture were studied on a total of 37 samples,
      collected from two brackish-water coastal basins: Fogliano Lake and Lungo Lake
      (central Italy). The research was performed as a preliminary low-cost survey to
      highlight the degree of the environmental stress and to recognize a possible
      anthropogenic disturbance. The sedimentological and foraminiferal data were
      processed by bivariate and multivariate statistical analysis. Three distinct
      assemblages, referable to different environments were recognized for the Fogliano
      Lake: inner, intermediate and outer lagoon. Only the outer lagoon assemblage was
      found in the Lungo Lake. The distribution of foraminifera in the Fogliano Lake
      suggests a natural environmental stress probably due to the ecological
      instability typical of marginal environments, while the absence of the inner and
      intermediate lagoon assemblages in the Lungo Lake suggests an environmental
      disturbance possibly related to human activities. An interdisciplinary survey
      including geochemical analyses is recommended in order to deduce the nature and
      degree of pollution in the Lungo Lake.

PMID- 19766257
TI  - The ecological sustainability trigon--a proposed conceptual framework for
      creating and testing management scenarios.
AB  - The ability to achieve ecological sustainability and the sustainable development
      of marine and estuarine ecosystems constitutes a complex major challenge and
      depends on many driving forces, often conflicting with each other. In particular,
      there are three major drivers: (a) the search for human well-being, health and
      safety, (b) the maintenance of ecological sustainability and environmental
      equilibrium, and (c) the tolerance of an increasing human population pressure and
      demand for wealth creation. We propose here the use of a conceptual guidance tool
      -the ecological sustainability trigon (EST)--as a means of building and testing
      environmental management scenarios. Although it requires further testing, the EST
      allows us to (a) address those three major drivers using human society view as a
      common currency, and (b) describe our behaviour, energetics (economy) and
      dynamics through ecological theory. Moreover, the EST appears promising for gap
      analysis and the means to address new research questions.

PMID- 19766258
TI  - [Concomitant diagnosis of acute myeloid leukaemia and chronic lymphoproliferative
      disorder with AA amyloidosis as a final event].

PMID- 19766259
TI  - [Multidisciplinary model of an early diagnosis outpatients unit].

PMID- 19766260
TI  - [New regulation on drug access under special circumstances in Spain].

PMID- 19766261
TI  - [Compassionate use of off-label drugs: need for a change in Spain].

PMID- 19766262
TI  - [Usefulness of molecular analysis in the differential diagnosis of congenital 21
      hidroxylase deficiency detected in neonatal screening].

PMID- 19766263
TI  - Measurement of cerebral oxidative glucose consumption in patients with type 1
      diabetes mellitus and hypoglycemia unawareness using (13)C nuclear magnetic
      resonance spectroscopy.
AB  - The aim of the present study was to use (13)C nuclear magnetic resonance (NMR) to
      measure the cerebral oxidative metabolic rate of glucose (CMRglc[ox]) in patients
      with diabetes and to compare these measurements with those collected from matched
      controls. We elected to study a group with type 1 diabetes mellitus and
      hypoglycemia unawareness because we had previously found such patients to have
      higher brain glucose concentrations than healthy volunteers under steady-state
      conditions. We sought to determine if this difference in steady-state brain
      concentrations could be explained by a difference in CMRglc(ox). Time courses of
      (13)C label incorporation in brain amino acids were measured in occipital cortex
      during infusion of [1-(13)C]glucose. These time courses were fitted using a 1
      compartment metabolic model to determine CMRglc(ox). Our results show that the
      tricarboxylic acid cycle (TCA) cycle rate (V(TCA), which is twice CMRglc[ox]) in
      subjects with type 1 diabetes mellitus was not significantly different from that
      of healthy controls (0.84 +/- 0.03 vs 0.79 +/- 0.03 micromol/[g min], n = 5 in
      each group, mean +/- SEM). We conclude that the changes in steady-state brain
      glucose concentrations that we observed in patients with type 1 diabetes mellitus
      in a previous study (J Neurosci Res. 2005;79:42-47) cannot be explained by
      changes in oxidative glucose consumption.

PMID- 19766264
TI  - Changes of peripheral alpha-melanocyte-stimulating hormone in childhood obesity.
AB  - Relationships of blood circulating melanocortins to childhood obesity are not
      well established. We evaluated serum alpha-melanocyte-stimulating hormone (alpha
      MSH) in lean children and different study groups of childhood obesity. We
      examined serum alpha-MSH in 52 otherwise healthy children with childhood obesity
      (Ob; mean age, 11 years; 32 girls/20 boys), 27 normal-weight children of same
      age, 7 additional obese patients with reduced melanocortin-4 receptor function
      (MC4Rmut), and 22 patients with craniopharyngioma (CP). Fasting serum alpha-MSH
      and leptin were measured by radioimmunoassay. Serum alpha-MSH was also evaluated
      1 hour after 500-kcal liquid meal (CP and Ob) and at the end of 1-year lifestyle
      intervention in 24 Ob patients. The alpha-MSH levels were similar in obese vs
      lean children but significantly lower in CP (P < .001) and significantly higher
      (P < .05) in MC4Rmut patients compared with Ob. One hour after liquid meal, alpha
      MSH increased in patients with Ob but not with CP. After 1 year, alpha-MSH levels
      increased significantly in the successful weight reduction Ob subgroup despite
      unchanged cortisol levels. The alpha-MSH changes correlated to weight status
      changes (r = 0.67, P = .0003) but not to changes of cortisol, insulin, or
      homeostasis model assessment of insulin resistance index. Persistently low alpha
      MSH levels in CP patients are suspected to be due to pituitary or hypothalamic
      damage. High peripheral levels in MC4Rmut carriers indicate up-regulation of
      alpha-MSH. Changes of weight status are associated with changes of peripheral
      alpha-MSH.

PMID- 19766265
TI  - Glucocorticoids and body fat associated with renal uric acid and oxalate, but not
      calcium excretion, in healthy children.
AB  - In patients with hypercortisolism, who are frequently obese, the prevalence of
      elevated urinary excretion rates of the potential lithogenic factors (calcium,
      oxalate, and uric acid) is increased. We examined whether the 24-hour urinary
      excretion rates of calcium, oxalate, and uric acid are already associated with
      body fat and endogenous glucocorticoids in healthy free-living children, taking
      relevant nutritional and acid-base factors into account. Urinary analyte
      excretions were determined in 24-hour urine samples of 300 healthy children aged
      4 to 14 years. Potentially bioactive free glucocorticoids were assessed as
      urinary free cortisol + urinary free cortisone. Associations of glucocorticoids
      and percentage body fat with the outcome variables were examined in regression
      models adjusted for sex, height, growth velocity, urinary volume, net acid
      excretion, and relevant nutritional factors. Percentage body fat and urinary free
      cortisol + urinary free cortisone explained most of the growth-independent
      variation of urinary uric acid and also a relevant part of oxalate, but none of
      calcium. Net acid excretion, an indicator of endogenous acid production, and
      dietary protein, salt, and fiber intakes were also variably associated with the
      outcomes urinary calcium, oxalate, and uric acid. In conclusion, body fatness and
      potentially bioactive free glucocorticoids (even in the physiologic range) appear
      to affect urinary excretion rates of oxalate and uric acid, whereas urinary
      calcium output is more strongly related to dietary factors in healthy children.
      Our data provide the first in vivo-based evidence that the obesity- or
      hypercortisolism-associated urolithiasis may be a pathophysiologic continuation
      of the corresponding endocrine metabolic variations in healthy children.

PMID- 19766266
TI  - Preliminary report: pharmacologic 11beta-hydroxysteroid dehydrogenase type 1
      inhibition increases hepatic fat oxidation in vivo and expression of related
      genes in rats fed an obesogenic diet.
AB  - This study aimed to explore in a model of diet-induced steatosis the impact of
      pharmacologic 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1)
      inhibition, under conditions of unchanged ingestive behavior, on liver fat
      oxidation. Male Sprague-Dawley rats were fed an obesogenic diet and were
      continuously treated or not with an 11beta-HSD1 inhibitor (Compound A, 3 mg/[kg
      d]; Merck Research Laboratories, Rahway, NJ), after which liver expression of
      oxidative genes and in vivo hepatic fat oxidation were quantified. Treatment with
      Compound A reduced liver triglyceride concentration (-28%), increased hepatic
      expression of several genes coding for enzymes of mitochondrial and peroxisomal
      beta-oxidation, and concomitantly enhanced in vivo liver fat oxidation (+38%).
      The study demonstrates, under conditions that avoided changes in food intake seen
      in gene knockout or higher-dose pharmacologic models, the efficacy of 11beta-HSD1
      inhibition to up-regulate hepatic fat oxidation gene expression, which
      functionally translates into enhanced hepatic lipid oxidation in vivo.

PMID- 19766268
TI  - Polyunsaturated fatty acids effect on serum triglycerides concentration in the
      presence of metabolic syndrome components. The Alaska-Siberia Project.
AB  - Serum fatty acids (FAs) have wide effects on metabolism: Serum saturated fatty
      acids (SFAs) increase triglyceride (TG) levels in plasma, whereas polyunsaturated
      fatty acids (PUFAs) reduce them. Traditionally, Eskimos have a high consumption
      of omega-3 fatty acids (omega3 FAs); but the Westernization of their food habits
      has increased their dietary SFAs, partly reflected in their serum concentrations.
      We studied the joint effect of serum SFAs and PUFAs on circulating levels of TGs
      in the presence of metabolic syndrome components. We included 212 men and 240
      women (age, 47.9 +/- 15.7 years; body mass index [BMI], 26.9 +/- 5.3) from 4
      villages located in Alaska for a cross-sectional study. Generalized linear models
      were used to build surface responses of TG as functions of SFAs and PUFAs
      measured in blood samples adjusting by sex, BMI, and village. The effects of
      individual FAs were assessed by multiple linear regression analysis, and partial
      correlations (r) were calculated. The most important predictors for TG levels
      were glucose tolerance (r = 0.116, P = .018) and BMI (r = 0.42, P < .001).
      Triglyceride concentration showed negative associations with 20:3omega6 (r = 
      0.16, P = .001), 20:4omega6 (r = -0.14, P = .005), 20:5omega3 (r = -0.17, P <
      .001), and 22:5omega3 (r = -0.26, P < .001), and positive associations with
      palmitic acid (r = 0.16, P < .001) and 18:3omega3 (r = 0.15, P < .001). The
      surface response analysis suggested that the effect of palmitic acid on TG is
      blunted in different degrees according to the PUFA chemical structure. The long
      chain omega3, even in the presence of high levels of saturated fat, was
      associated with lower TG levels. Eicosapentaenoic acid (20:5omega3) had the
      strongest effect against palmitic acid on TG. The total FA showed moderate
      association with levels of TG, whereas SFA was positively associated and large
      chain PUFA was negatively associated. The Westernized dietary habits among
      Eskimos are likely to change their metabolic profile and increase comorbidities
      related to metabolic disease.

PMID- 19766269
TI  - Altered metabolisms of mediators controlling vascular function and enhanced
      oxidative stress in asymptomatic children with congenital portosystemic venous
      shunt.
AB  - Children with congenital portosystemic venous shunt (PSVS) are at risk for
      developing pulmonary hypertension, irrespective of the severity of portal
      hypertension or liver damage. Altered metabolisms of nitric oxide (NO) and
      endothelin-1 (ET-1), which are linked with oxidative stress and control vascular
      tone, might contribute to the vascular disturbance. This study examined 14
      children (aged 1-5 years) with congenital PSVS lacking major liver damage and
      portal hypertension. Serum levels of nitrite/nitrate (NOx) as stable metabolites
      of NO, and of asymmetric dimethylarginine (ADMA) as an endogenous NO synthase
      inhibitor were determined, along with the plasma level of ET-1. Oxidative stress,
      which might affect the production of such mediators, was also examined using
      specific urinary and blood markers. The NOx levels were significantly lower in
      affected children than in the age-matched control group, although ET-1 levels
      were significantly higher than the control levels. In the affected children, the
      ADMA levels and ADMA/NOx ratios were higher, respectively, by 30% and 130% and
      showed significant positive correlations with the shunt ratios. Oxidative stress
      markers, including plasma thiobarbiturate reactive substances and urinary
      acrolein-lysine and 8-hydroxy-2'-deoxyguanosine, were significantly higher in
      affected children than in the control group, consistent with them being subjected
      to enhanced oxidative stress. These results suggest the presence of altered
      metabolisms of vascular mediators and enhanced oxidative stress in asymptomatic
      preschool children with congenital PSVS.

PMID- 19766267
TI  - Skeletal muscle insulin resistance: the interplay of local lipid excess and
      mitochondrial dysfunction.

PMID- 19766270
TI  - The role of proliferator-activated receptor gamma coactivator-1alpha in the fatty
      acid-dependent transcriptional control of interleukin-10 in hepatic cells of
      rodents.
AB  - Interleukin-10 (IL-10) is an endogenous factor that restrains hepatic insulin
      resistance in diet-induced steatosis. Reducing IL-10 expression increases
      proinflammatory activity in the steatotic liver and worsens insulin resistance.
      As the transcriptional coactivator proliferator-activated receptor gamma
      coactivator-1alpha (PGC-1alpha) plays a central role in dysfunctional hepatocytic
      activity in diet-induced steatosis, we hypothesized that at least part of the
      action of PGC-1alpha could be mediated by reducing the transcription of the IL-10
      gene. Here, we used immunoblotting, real-time polymerase chain reaction,
      immunocytochemistry, and chromatin immunoprecipitation assay to investigate the
      role of PGC-1alpha in the control of IL-10 expression in hepatic cells. First, we
      show that, in the intact steatotic liver, the expressions of IL-10 and PGC-1alpha
      are increased. Inhibiting PGC-1alpha expression by antisense oligonucleotide
      increases IL-10 expression and reduces the steatotic phenotype. In cultured
      hepatocytes, the treatment with saturated and unsaturated fatty acids increased
      IL-10 expression. This was accompanied by increased association of PGC-1alpha
      with c-Maf and p50-nuclear factor (NF) kappaB, 2 transcription factors known to
      modulate IL-10 expression. In addition, after fatty acid treatment, PGC-1alpha, c
      Maf, and p50-NFkappaB migrate from the cytosol to the nuclei of hepatocytes and
      bind to the IL-10 promoter region. Inhibiting NFkappaB activation with salicylate
      reduces IL-10 expression and the association of PGC-1alpha with p50-NFkappaB.
      Thus, PGC-1alpha emerges as a potential transcriptional regulator of the
      inflammatory phenomenon taking place in the steatotic liver.

PMID- 19766271
TI  - Elevated serum retinol-binding protein 4 is associated with insulin resistance in
      older women.
AB  - Retinol-binding protein 4 (RBP4), a molecule secreted from adipocytes and
      hepatocytes, may contribute to insulin resistance and is a potential predictor
      for type 2 diabetes mellitus. We investigated the association between serum RBP4
      concentrations and insulin resistance in perimenopausal women. In addition, we
      examined associations of serum RBP4 concentrations with age, risk factors of
      cardiovascular disease, and metabolic syndrome. A total of 73 healthy women were
      included in this study. Subjects' anthropometric measurements were taken, and
      body mass index and waist-hip ratio were calculated. Fasting glucose, fasting
      insulin, serum RBP4, and lipid parameters were examined. These various parameters
      were compared in subjects younger than and older than 50 years. Serum RBP4
      concentrations in women at least 50 years of age were significantly higher than
      those in women younger than 50 years. In all subjects, serum RBP4 concentrations
      positively correlated with age, diastolic blood pressure, fasting glucose, and
      homeostatic assessment model of insulin resistance. After subgroup analysis,
      serum RBP4 concentrations positively correlated with age, fasting glucose, and
      homeostatic assessment model of insulin resistance in women at least 50 years of
      age. In women younger than 50 years, serum RBP4 concentrations positively
      correlated only with fasting glucose. Serum RBP4 appears to identify age-induced
      insulin resistance by physiologic changes due to aging or menopause and by
      increasing hepatic glucose production. However, the clinical implication of RBP4
      for detecting cardiovascular disease and metabolic syndrome is not clear.

PMID- 19766272
TI  - Exendin-4 and exercise improve hepatic glucose homeostasis by promoting insulin
      signaling in diabetic rats.
AB  - Recently, it has been reported that a long-acting glucagon-like peptide-1
      (exendin-4) and physical exercise improve hepatic insulin action in diabetic
      rats. However, this phenomenon remains poorly understood. We investigated the
      long-term effect that exendin-4 and exercise had on hepatic insulin resistance
      through the modulation of hepatic and/or hypothalamic insulin signaling in 90%
      pancreatectomized diabetic rats fed 40% energy fat diets. The rats were divided
      into 4 groups: exendin-4 only, exendin-4 plus exercise training, saline
      (control), or exercise training only. Rats in the exendin-4 groups were
      administered with 150 pmol/kg exendin-4 twice a day for 8 weeks, whereas those in
      the exercise groups ran on an uphill treadmill with a 15 degrees incline at 20
      m/min for 30 minutes 5 days a week. Exendin-4 reduced serum glucagon levels in
      overnight-fasted rats. Exendin-4 treatment by itself decreased hepatic glucose
      output at hyperinsulinemic states, and exercise without exendin-4 treatment also
      had the same effect. Exendin-4 promoted hepatic insulin signaling by potentiating
      tyrosine phosphorylation of the insulin receptor substrate-2 without changing
      hypothalamic insulin signaling. Exendin-4 also enhanced hypothalamic glucose
      sensing. However, exercise improved both hepatic and hypothalamic insulin
      signaling by activating the phosphorylation of cyclic adenosine monophosphate
      responding element binding proteins to induce insulin receptor substrate-2
      expression. Exendin-4 and exercise decreased the expression of
      phosphoenolpyruvate carboxykinase, which in turn reduced hepatic glucose output.
      Exendin-4 in combination with exercise had no additive effects. In conclusion,
      exendin-4 and exercise improve hepatic glucose homeostasis by promoting hepatic
      insulin signaling in diabetic rats.

PMID- 19766273
TI  - Increased left ventricular arrhythmogenicity in metabolic syndrome and
      relationship with myocardial performance, risk factors for atherosclerosis, and
      low-grade inflammation.
AB  - Metabolic syndrome (MetS) is a clustering of cardiovascular risk factors recently
      associated with left ventricular dysfunction. Limited data exist on the
      association between MetS and ventricular arrhythmogenicity. This study examined
      differences in ventricular arrhythmogenicity assessed by classic (QT interval)
      and newer (spatial QRS-T angle [spQRS-Ta]) electrocardiographic markers in
      subjects with and without MetS. A total of 306 subjects, 153 with and 153 without
      MetS, matched for sex and age were examined. The spQRS-Ta, which
      vectorcardiographically quantifies the deviation between the directions of
      ventricular depolarization and repolarization, was measured using a computer
      based electrocardiograph. Left ventricular mass index and myocardial performance
      were evaluated echocardiographically. The spQRS-Ta was significantly higher in
      subjects with in comparison with those without MetS. Left ventricular mass index,
      QT interval, and its dispersion were not different between the 2 groups. Left
      ventricular myocardial performance was worse in subjects with MetS and was
      associated with higher values of the spQRS-Ta. Multivariate linear regression
      analysis demonstrated MetS status as the strongest predictor of ventricular
      arrhythmogenicity. Addition of the high-sensitivity C-reactive protein in the
      model increased the explained variance of the spQRS-Ta by 11%. In conclusion,
      ventricular arrhythmogenicity is present in MetS and is associated with
      myocardial dysfunction, risk factors for atherosclerosis, and low-grade
      inflammation. The independent association between the spQRS-Ta and MetS implies
      that the clustering of the metabolic disturbances has additional prognostic
      information than its individual components in terms of ventricular
      arrhythmogenicity and may explain in part the excess cardiovascular risk in
      subjects with MetS.

PMID- 19766274
TI  - Sesquiterpenoids from Teucrium ramosissimum.
AB  - An antiplasmodial bioguided investigation of the EtOAc extract of the aerial
      parts of Teucrium ramosissimum led to isolation and identification of three
      sesquiterpenoids, teucmosin, 4alpha-hydroxy-homalomenol C, 1beta,4beta,7alpha
      trihydroxy-8,9-eudesmene and two trinorsesquiterpenoids, 4beta-hydroxy-11,12,13
      trinor-5-eudesmen-1,7-dione and 1beta,4beta-dihydroxy-11,12,13-trinor-8,9
      eudesmen-7-one together with five known sesquiterpenoids, oplopanone, homalomenol
      C, oxo-T-cadinol, 1beta,4beta,6beta-trihydroxyeudesmane, 1beta,4beta,7alpha
      trihydroxyeudesmane and four flavonoids, 5-hydroxy-7,4'-dimethoxyflavone,
      salvigenin, genkwanin and cirsimaritin. The structures and the relative
      stereochemistry were elucidated by extensive spectroscopic studies including 1D
      and 2D NMR and mass spectrometry (MS). Homalomenol C, 4beta-hydroxy-11,12,13
      trinor-5-eudesmen-1,7-dione, oxo-T-cadinol and 1beta,4beta,6beta
      trihydroxyeudesmane displayed a significant in vitro antiplasmodial activity
      against Plasmodium falciparum with IC(50) values ranging from 1.2 to 5.0
      microg/ml. Furthermore, no cytotoxicity was observed upon the human diploid lung
      cell line MRC-5 for these compounds.

PMID- 19766275
TI  - A rapid method for depletion of Rubisco from soybean (Glycine max) leaf for
      proteomic analysis of lower abundance proteins.
AB  - 2-DE analysis of complex plant proteomes has limited dynamic resolution because
      only abundant proteins can be detected. Proteomic assessment of the low abundance
      proteins within leaf tissue is difficult when it is comprised of 30-50% of the
      CO(2) fixation enzyme Rubisco. Resolution can be improved through depletion of
      Rubisco using fractionation techniques based upon different physiological or
      biochemical principles. We have developed a fast and simple fractionation
      technique using 10 mM Ca(2+) and 10 mM phytate to precipitate Rubisco from
      soybean leaf soluble protein extract. This method is not only rapid, but also
      inexpensive, and capable of removing 85% of the extremely abundant Rubisco enzyme
      from soybean leaf soluble protein extract. This method allowed for roughly 230
      previously inconspicuous protein spots in soybean leaf to be more easily
      detectable (3-fold increase in vol%) using fluorescent detection and allowed 28
      phosphorylated proteins previously undetected, to be isolated and identified by
      MALDI-TOF-MS.

PMID- 19766276
TI  - Xanthones from Hypericum chinense and their cytotoxicity evaluation.
AB  - A xanthonolignoid, 2-O-demethylkielcorin, and a phenylxanthone, chinexanthone A,
      were isolated from stems of Hypericum chinense together with four known
      xanthonolignoids and seven known xanthones. Their structures were established by
      spectroscopic analysis, as their optical properties and absolute stereochemistry
      determined. The cytotoxicities of the isolated xanthone derivatives as well as
      additional 32 xanthones against a panel of human cancer cell lines were also
      evaluated.

PMID- 19766277
TI  - Changes in tuberculin sensitivity among first-grade students of elementary
      schools in Evros, Greece due to immigration.
AB  - OBJECTIVE: To investigate the tuberculin sensitivity trends among first-grade
      students of elementary schools tested according to the Greek national school
      based screening and vaccination programme. STUDY DESIGN: Retrospective analysis
      of tuberculin skin test (TST) results from 1988 to 2004 in unvaccinated first
      grade students in Evros, Greece. METHODS: All 6-7-year-old children who were
      unvaccinated for tuberculosis were tested by a highly experienced team. This
      study tested whether gender (male vs female), national origin (native vs foreign
      born children) and place of residence (urban vs semi-urban vs rural) correlated
      with tuberculin reaction positivity. RESULTS: In total, 8588 children (47.1%
      girls) were tested. Tuberculin reaction positivity was independent of gender. The
      difference in TST positivity between native and foreign-born children between
      1993 and 2004 was highly significant, with substantially more foreign-born
      children having a positive Mantoux test (P<0.0001). The percentage of children
      with a positive TST peaked at 13% in 1995 due to initial admission of foreign
      born children, originating from countries of the former Soviet Union, into the
      Greek educational system. In addition, a positive Mantoux test was more common
      among children living in rural (8.1%) and semi-urban (6.4%) areas compared with
      children living in urban areas (3.5%, P<0.0001). CONCLUSION: The increase in TST
      positivity noted was due to admission of foreign-born children into the Greek
      educational system. School-based tuberculosis screening programmes should
      continue in Greece because the prevalence of tuberculosis appears to show
      substantial variation between years.

PMID- 19766278
TI  - An evaluation of an attempt to change the snacking habits of pre-school children
      using social marketing.
AB  - OBJECTIVES: To demonstrate the feasibility and value of social marketing over a
      wide geographical footprint, and to improve the snacking habits of pre-school
      children. STUDY DESIGN: Two cross-sectional studies before and approximately 3
      months after a social marketing intervention targeted into the least affluent
      areas using convenience sampling. METHODS: Based on market research and directed
      at the least affluent areas, a brand was created ('Snack Right') and an
      information leaflet was distributed, supported by a media launch and events at
      children's centres in targeted areas. This evaluation of some aspects of the
      project is based on a questionnaire delivered before and after the events.
      RESULTS: There were several differences in pre- and post-event responses
      consistent with the messages delivered, for example increased spending on fruit
      (but not vegetables) and more positive attitudes towards fruits and vegetables.
      Some ambiguities were exposed, for example towards snacking, which have
      implications for the nutritional knowledge of health professionals. The Snack
      Right brand was recalled by a very high proportion of respondents at follow-up.
      CONCLUSIONS: This project has shown that social marketing is a viable tool at a
      subregional level and has the potential to change attitudes, knowledge and
      behaviour.

PMID- 19766279
TI  - Chromoblastomycosis in Sarawak, East malaysian Borneo.
AB  - A retrospective study was conducted to determine the clinical characteristics and
      treatment outcomes of 11 new patients with a histological diagnosis of
      chromoblastomycosis at Sarawak General Hospital, Malaysia, between 1996 and 2008.
      The majority (81.8%) were males, and the median age at presentation was 40 years.
      Over half the patients were farmers. All the patients had irregular verrucous
      lesions, mostly on the lower limbs (90.9%), and had initially been misdiagnosed.
      The mean duration of the lesions was 13.8 years. Oral terbinafine and
      itraconazole were administered to all the patients; clinical cure was seen in
      54.5%, and partial response in 18.2%. Concomitant electrocautery and cryotherapy
      were only effective for small lesions.

PMID- 19766280
TI  - Changes of the receptor-binding properties of influenza B virus
      B/Victoria/504/2000 during adaptation in chicken eggs.
AB  - Selection of high-growth virus variants of strain B/Victoria/504/2000 by serial
      passage in eggs resulted in three amino acid substitutions, G141E, R162M, and
      D196Y, in the vicinity of the receptor-binding pocket of viral hemagglutinin.
      Virus variants containing the identified amino acid substitutions, individually
      or in various combinations, were constructed using reverse genetics and analyzed
      for their receptor-binding properties using glycan microarray platform. Three
      different patterns of virus binding were revealed. A low-growth virus variant,
      corresponding to the original egg-derived virus B/Victoria/504/2000 prior to
      acquisition of amino acid changes G141E, R162M, and D196Y, had a clear preference
      for the oligosaccharide chains terminated with alpha2-6-linked sialic acid with
      very weak binding of the glycans terminated with alpha2-3-linked sialic acid.
      Amino acid substitutions R162M and D196Y had similar effects, resulting in
      viruses that bound with high efficiency almost all terminally sialylated glycans
      represented on the array regardless of the type of glycosidic linkage. In
      contrast, substitution of G141E alone, or in combinations with the other two
      amino acid substitutions, significantly restricted virus glycan-binding
      capabilities. All virus variants possessing this substitution lost the ability to
      bind glycans with alpha2-6 glycosidic linkage as well as most of the glycans with
      alpha2-3 glycosidic linkage. Linear penta- and heptasaccharide chains represented
      at the non-reducing end by alpha2-3 sialylated Type-II motif (LacNAc) were the
      only structures bound with high affinity by the virus variants with G141E
      substitution. In all cases when the effects on virus binding of individual amino
      acid substitutions differed, the effect of R162M was subordinate to the effect of
      either G141E or D196Y.

PMID- 19766281
TI  - Nuclear location of minor capsid protein L2 is required for expression of a
      reporter plasmid packaged in HPV51 pseudovirions.
AB  - The deduced amino acid (aa) sequence of L2 of the newly sequenced HPV51 strain,
      isolated by Matsukura and Sugase (Ma-strain), was markedly different from that of
      the prototype HPV51 isolated by Nuovo et al. (Nu-strain) (GenBank M62877) in two
      regions: aa 95-99 (region I) and aa 179-186 (region II). The two regions of Ma
      strain were homologous to those of the other mucosal HPVs. The aa sequences of
      the N-terminal and C-terminal regions of Ma-L2 and Nu-L2 were identical and
      contained the nuclear localizing signal (NLS). When expressed in HEK293 cells, Ma
      strain L2 (Ma-L2) was located in the nucleus but Nu-strain L2 (Nu-L2), in the
      cytoplasm. The chimeric L2s having both Nu-L2 regions I and II were located in
      the cytoplasm, and those having one of them were located both in the nucleus and
      cytoplasm, suggesting that Nu-L2 regions I and II inhibit the NLS function. For a
      better understanding of a role of L2 in infection, pseudovirion (PV) preparations
      were produced with a reporter, Ma-strain L1, and various L2s (Ma-L2, Nu-L2, or
      the chimeric L2s). These PV preparations contained structurally similar particles
      composed of L1 and L2 and the packaged reporter plasmid at a similar level. The
      reporter expression was not induced in HEK293 cells after inoculation with PVs
      containing the L2s that are incapable of localizing in the nucleus when expressed
      alone. Among PVs containing L2s capable of localizing in the nucleus, the
      reporter expression was induced only by PVs containing Ma-L2 region I. Thus, the
      results indicate that the expression of the reporter in the HPV51 PV requires the
      nuclear localizing ability of L2 and another unknown function associated with
      region I.

PMID- 19766282
TI  - Experimental evidence that RNA recombination occurs in the Japanese encephalitis
      virus.
AB  - Due to the lack of a proofreading function and error-repairing ability of genomic
      RNA, accumulated mutations are known to be a force driving viral evolution in the
      genus Flavivirus, including the Japanese encephalitis (JE) virus. Based on
      sequencing data, RNA recombination was recently postulated to be another factor
      associated with genomic variations in these viruses. We herein provide
      experimental evidence to demonstrate the occurrence of RNA recombination in the
      JE virus using two local pure clones (T1P1-S1 and CJN-S1) respectively derived
      from the local strains, T1P1 and CJN. Based on results from a restriction
      fragment length polymorphism (RFLP) assay on the C/preM junction comprising a
      fragment of 868 nucleotides (nt 10-877), the recombinant progeny virus was
      primarily formed in BHK-21 cells that had been co-infected with the two clones
      used in this study. Nine of 20 recombinant forms of the JE virus had a crossover
      in the nt 123-323 region. Sequencing data derived from these recombinants
      revealed that no nucleotide deletion or insertion occurred in this region
      favoring crossovers, indicating that precisely, not aberrantly, homologous
      recombination was involved. With site-directed mutagenesis, three stem-loop
      secondary structures were destabilized and re-stabilized in sequence, leading to
      changes in the frequency of recombination. This suggests that the conformation,
      not the free energy, of the secondary structure is important in modulating RNA
      recombination of the virus. It was concluded that because RNA recombination
      generates genetic diversity in the JE virus, this must be considered particularly
      in studies of viral evolution, epidemiology, and possible vaccine safety.

PMID- 19766283
TI  - Generation of monoclonal antibody that distinguishes PrPSc from PrPC and
      neutralizes prion infectivity.
AB  - To establish PrP(Sc)-specific mAbs, we immunized Prnp(-/-) mice with PrP(Sc)
      purified from prion-infected mice. Using this approach, we obtained mAb 6H10,
      which reacted with PrP(Sc) treated with proteinase K, but not with PrP(Sc)
      pretreated with more than 3 M GdnHCl. In contrast, reactivity of pan-PrP mAbs
      increased with increasing concentrations of GdnHCl used for pretreatment of
      PrP(Sc). In histoblot analysis, mAb 6H10 showed a positive reaction on a non
      denatured histoblot but reactivity was lower when the histoblot was pretreated by
      autoclaving. Epitope analysis suggested that the extreme C-terminus of PrP is
      likely to be part of the epitope for mAb 6H10. MAb 6H10 immunoprecipitated
      PrP(Sc) from brains of mice, sheep, and cattle infected with prions. Furthermore,
      pretreatment of purified PrP(Sc) with mAb 6H10 reduced the infectious titer more
      than 1 log. Taken together, these results suggest that mAb 6H10 recognizes a
      conformational epitope on PrP(Sc) that is related to prion infectivity.

PMID- 19766284
TI  - Peruvian horse sickness virus and Yunnan orbivirus, isolated from vertebrates and
      mosquitoes in Peru and Australia.
AB  - During 1997, two new viruses were isolated from outbreaks of disease that
      occurred in horses, donkeys, cattle and sheep in Peru. Genome characterization
      showed that the virus isolated from horses (with neurological disorders, 78%
      fatality) belongs to a new species the Peruvian horse sickness virus (PHSV),
      within the genus Orbivirus, family Reoviridae. This represents the first
      isolation of PHSV, which was subsequently also isolated during 1999, from
      diseased horses in the Northern Territory of Australia (Elsey virus, ELSV).
      Serological and molecular studies showed that PHSV and ELSV are very similar in
      the serotype-determining protein (99%, same serotype). The second virus (Rioja
      virus, RIOV) was associated with neurological signs in donkeys, cattle, sheep and
      dogs and was shown to be a member of the species Yunnan orbivirus (YUOV). RIOV
      and YUOV are also almost identical (97% amino acid identity) in the serotype
      determining protein. YUOV was originally isolated from mosquitoes in China.

PMID- 19766285
TI  - Toxicological relevance of emerging contaminants for drinking water quality.
AB  - The detection of many new compounds in surface water, groundwater and drinking
      water raises considerable public concern, especially when human health based
      guideline values are not available it is questioned if detected concentrations
      affect human health. In an attempt to address this question, we derived
      provisional drinking water guideline values for a selection of 50 emerging
      contaminants relevant for drinking water and the water cycle. For only 10
      contaminants, statutory guideline values were available. Provisional drinking
      water guideline values were based upon toxicological literature data. The maximum
      concentration levels reported in surface waters, groundwater and/or drinking
      water were compared to the (provisional) guideline values of the contaminants
      thus obtained, and expressed as Benchmark Quotient (BQ) values. We focused on
      occurrence data in the downstream parts of the Rhine and Meuse river basins. The
      results show that for the majority of compounds a substantial margin of safety
      exists between the maximum concentration in surface water, groundwater and/or
      drinking water and the (provisional) guideline value. The present assessment
      therefore supports the conclusion that the majority of the compounds evaluated
      pose individually no appreciable concern to human health.

PMID- 19766286
TI  - Adsorption of rotavirus and bacteriophage MS2 using glass fiber coated with
      hematite nanoparticles.
AB  - Batch and flow-through experiments were conducted to investigate the removal and
      inactivation of rotavirus (RV) and bacteriophage MS2 using glass fiber coated
      with hematite nanoparticles. Batch tests showed a high removal of MS2
      (2.49x10(11) plaque forming unit/g) and RV (8.9x10(6) focal forming unit/g) at a
      low concentration of hematite nanoparticles in solution (0.043g/L and 0.26g/L,
      respectively). Virus adsorption was, however, decreased in the presence of
      bicarbonate ions and natural organic matter (NOM) in solution, suggesting a great
      affinity of iron oxide nanoparticles for these competitors. Adsorption on
      hematite nanoparticles by MS2 and RV was also tested with aquifer groundwater
      under saturated flow conditions to mimic environmental conditions with promising
      results (8x10(8) plaque forming unit/g and 3x10(4) focal forming unit/g,
      respectively). Desorption of up to 63% of infectious MS2 and only 2% of
      infectious RV from hematite nanoparticles were achieved when an eluant solution
      containing beef extract and glycine was used. Transmission electron microscopy
      (TEM) images showed evidence of electrostatic adsorption of apparently intact MS2
      and structurally damaged RV particles to hematite nanoparticles. Results from
      this research suggest that a cartridge made of glass fiber coated with hematite
      nanoparticles could be used as a point-of-use device for virus removal for
      drinking water treatment.

PMID- 19766287
TI  - Modelling the removal of p-TSA (para-toluenesulfonamide) during rapid sand
      filtration used for drinking water treatment.
AB  - A finite element model was set-up to determine degradation rate constants for p
      TSA during rapid sand filtration (RSF). Data used for the model originated from a
      column experiment carried out in the filter hall of a drinking water treatment
      plant in Berlin (Germany). Aerated abstracted groundwater was passed through a
      1.6m long column-shaped experimental sand filter applying infiltration rates from
      2 to 6mh(-1). Model results were fitted to measured profiles and breakthrough
      curves of p-TSA for different infiltration rates using both first-order reaction
      kinetics and Michaelis-Menten kinetics. Both approaches showed that degradation
      rates varied both in space and time. Higher degradation rates were observed in
      the upper part of the column, probably related to higher microbial activity in
      this zone. Measured and simulated breakthrough curves revealed an adaption phase
      with lower degradation rates after infiltration rates were changed, followed by
      an adapted phase with more elevated degradation rates. Irrespective of the
      mathematical approach and the infiltration rate, degradation rates were very
      high, probably owing to the fact that filter sands have been in operation for
      decades, receiving high p-TSA concentrations with the raw water.

PMID- 19766288
TI  - Modelling bioaccumulation of semi-volatile organic compounds (SOCs) from air in
      plants based on allometric principles.
AB  - A model was developed for gaseous plant-air exchange of semi-volatile organic
      compounds. Based on previous soil-plant modelling, uptake and elimination
      kinetics were scaled as a function of plant mass and octanol-air partition
      ratios. Exchange of chemicals was assumed to be limited by resistances
      encountered during diffusion through a laminar boundary layer of air and
      permeation through the cuticle of the leaf. The uptake rate constant increased
      and the elimination rate constant decreased with the octanol-air partition ratio
      both apparently levelling off at high values. Differences in kinetics between
      species could be explained by their masses. Validation on independent data showed
      that bio-concentration factors of PCBs, chlorobenzenes and other chemicals were
      predicted well by the model. For pesticides, polycyclic aromatic hydrocarbons and
      dioxins deviations occurred.

PMID- 19766289
TI  - An assessment of the human health risks from exposure to polybrominated diphenyl
      ethers (PBDEs) in house dust.

PMID- 19766290
TI  - Relationship between urinary metabolites of polycyclic aromatic hydrocarbons and
      thyroid hormone levels in Chinese non-occupational exposure adult males.
AB  - Polycyclic aromatic hydrocarbons (PAH) are ubiquitous global pollutants. Limited
      studies suggested that PAH may interfere with thyroid function in animals, but
      little is known about humans. A population of 480 Chinese males was recruited.
      Using LC-MS/MS, four urinary metabolites of PAH including 1-hydroxynaphthalene (1
      N), 2-hydroxynaphthalene (2-N), 1-hydroxypyrene (1-P) and 2-hydroxyfluorene (2-F)
      were measured in spot urinary samples, which were adjusted by urinary creatinine
      (CR). Blood samples were collected for measuring serum levels of thyroid hormones
      including total thyroxine (TT4), free triiodothyronine (FT3), free thyroxine
      (FT4) and thyroid-stimulating hormone (TSH). The median CR-adjusted urine PAH
      concentrations of 1-N, 2-N, 1-P, 2-F were 2.306, 4.047, 1.155 and 2.899 microg g(
      1) of CR, respectively. Significant p-values for trend were found for men with
      higher 2-F tertiles and were more likely to possess high-reference TSH levels. In
      addition, the multivariate linear regression models showed significant positive
      correlations for TSH levels with increased CR-adjusted 2-F concentration. No
      significant associations were found between other thyroid hormones levels and PAH
      metabolite concentrations. These results indicated that PAH exposure might be
      related to altered male thyroid hormone levels, but further study is needed to
      confirm these observed findings.

PMID- 19766291
TI  - A conceptual model describing the fate of sulfadiazine and its metabolites
      observed in manure-amended soils.
AB  - Sulfadiazine (SDZ) belongs to the chemical class of sulfonamides, one of the most
      important groups of antibiotics applied in animal husbandry in Europe. These
      antibiotics end up in the soil after manure from treated animals is applied as
      fertilizer. They can inhibit soil microbial functions and enhance the spread of
      resistance genes among soil microorganisms. In order to assess the exposure of
      soil microorganisms to SDZ, a conceptual kinetic model for the prediction of
      temporally resolved antibiotic concentrations in soil was developed. The model
      includes transformation reactions, reversible sequestration and the formation of
      non-extractable residues (NER) from SDZ and its main metabolites N(4)-acetyl
      sulfadiazine (N-ac-SDZ) and 4-hydroxy-sulfadiazine (OH-SDZ). The optimum model
      structure and rate constants of SDZ kinetics and its metabolites were determined
      by fitting different model alternatives to sequential extraction data of a manure
      amended Cambisol soil. N-ac-SDZ is degraded to SDZ with a half-life of 4d,
      whereas OH-SDZ is not. Though, based on the available data, the hydroxylation of
      SDZ seems to be negligible, it is still included in the model structure since
      this process has been observed in recent studies. Sequestration into a residual
      fraction has similar kinetics for SDZ, N-ac-SDZ and OH-SDZ and is one order of
      magnitude faster than the reverse translocation. The irreversible formation of
      NER is restricted to SDZ and OH-SDZ. The model shows good agreement when applied
      to extraction data measured independently for a Luvisol soil. The combination of
      sequential extraction data and the conceptual kinetic model enables us to gain
      further insight into the long-term fate and exposure of sulfonamides in soil.

PMID- 19766292
TI  - Market survey on toxic metals contained in tattoo inks.
AB  - Tattooing practice is adopted worldwide and represents an important socio
      cultural phenomenon, but, the injection into the skin of coloring agents as
      metals might pose a risk for allergies and other skin inflammations as well as
      for systemic diseases. In this context, 56 inks for tattooing purchased from 4
      different supply companies were analyzed for metal concentration. Aliquots of
      pigments were microwave digested by nitric acid, fluoridric acid and hydrogen
      peroxide and Al, Ba, Cd, Co, Cr, Cu, Fe, Hg, Mn, Ni, Pb, Sb, Sr and V were
      quantified by sector field inductively coupled plasma mass spectrometry. Limits
      of quantification varied from 0.07 ng/ml (Cd) to 10 ng/ml (Al and Fe); recoveries
      ranged from 92% (Cd and Sb) to 109% (Sr); within- and between-day precisions were
      3.2% and 4.67% on average. The relative contribution of metals to the tattoo inks
      composition was highly variable between brands and colors, even in pigments with
      the same base color. Elements found as the main components of inks were as
      follows (in microg/g): Al, 1.59-5893; Ba, 0.058-1226; Cu, 0.076-31,310; Fe, 0.717
      88,443; Sr, 0.174-36.4. Toxic metals as Cd, Mn, Pb, Sb and V were over the 1
      microg/g in a few cases, while Hg was in traces. Among the allergenic metals, Cr
      was the highest (0.315-147 microg/g), followed by Ni (0.037-9.59 microg/g) and Co
      (0.0028-6.43 microg/g) then. On 56 tattoo inks, Cr, Ni and Co exceeded the safe
      allergological limit of 1 microg/g in 62.5%, 16.1% and 1.8% of cases,
      respectively.

PMID- 19766293
TI  - Long-term changes of mercury levels in ringed seal (Phoca hispida) from Amundsen
      Gulf, and beluga (Delphinapterus leucas) from the Beaufort Sea, western Canadian
      Arctic.
AB  - Mercury (Hg) concentrations were determined in the canine teeth of ringed seals
      (Phoca hispida) harvested during the 13th-14th, late 19th and early 21st
      Centuries in Amundsen Gulf, Northwest Territories, Canada. Most historical and
      pre-industrial teeth contained undetectable Hg levels (i.e. <1.0 ng/g DW),
      whereas samples from 2001-03 contained up to 12 ng/g DW in an age-dependent
      pattern. Assuming a median [Hg] value in 13th-14th Century teeth of half the
      detection limit (i.e. 0.5 ng/g DW), geometric means of Hg in modern teeth were 9
      17 times those of seals in the 14th Century, equivalent to an anthropogenic input
      of 89-94% of total Hg in modern seals. These results corroborate a previous study
      of beluga (Delphinapterus leucas) in the nearby Beaufort Sea. While the seals'
      trophic position (inferred from delta(15)N values) did not change over time,
      modern delta(13)C values were lower by about 2 per thousand than in the 14th and
      19th Centuries. This could be due to increased dissolution of anthropogenically
      derived CO(2) in the ocean from the atmosphere, but could also indicate more
      offshore pelagic feeding by modern seals, which might be a factor in their Hg
      exposure. New tooth [Hg] data are also presented for the Beaufort Sea beluga,
      using recently-discovered museum samples collected in 1960/61, which showed that
      most of the anthropogenic contribution to beluga Hg had already taken effect by
      1960 (reaching approximately 75% of total Hg). Taken together, the long-term seal
      and beluga data indicate that whereas Hg levels in the marine ecosystems of the
      western Canadian Arctic were probably unchanged from pre-industrial times up to
      the late 19th Century, there was a significant, many-fold increase in the early
      to mid-20th Century, but little or no change after about the early 1960s.

PMID- 19766294
TI  - Role of NMDA receptor in homocysteine-induced activation of mitogen-activated
      protein kinase and phosphatidyl inositol 3-kinase pathways in cultured human
      vascular smooth muscle cells.
AB  - INTRODUCTION: Exposure of vascular smooth muscle cells (VSMC) to homocysteine, at
      concentrations associated with an increased risk of cardiovascular events,
      enhances synthesis and secretion of Matrix Metalloproteinase-2 (MMP-2), which is
      involved in atherosclerotic plaque instabilization. This effect was prevented by
      inhibitors of Mitogen Activated Protein Kinase (MAPK) and Phosphatidylinositol 3
      Kinase (PI3-K) pathways, allowing to hypothesize that homocysteine activates both
      these pathways, likely via a receptor-mediated mechanism. One possible receptor
      is N-methyl-D-aspartate receptor (NMDAr), which is expressed in VSMC and is
      involved in homocysteine effects in other cell types. MATERIALS AND METHODS: VSMC
      exposed to DL-homocysteine or NMDA (100 micromol/L for both; 5 min-8 hours), were
      investigated by measuring: i) phosphorylation of ERK1/2, p38MAPK (signaling
      molecules of MAPK pathway) and Akt and p70S6K (signaling molecules of PI3-K
      pathway) by western blot; ii) synthesis and secretion of MMP-2 (western blot);
      iii) activation of MMP-2 (gelatin zimography). To evaluate NMDAr involvement in
      the homocysteine effects, the experiments were repeated in the presence of a non
      competitive NMDAr-antagonist MK-801 (50 micromol/L) or L-glycine (10 micromol/L),
      which inhibits NMDAr function by promoting its internalization. RESULTS: DL
      homocysteine and NMDA time-dependently increased: i) the phosphorylation of
      ERK1/2, p38 MAPK, Akt and p70S6K (ANOVA, p<0.0001); ii) the synthesis, secretion
      and activation of MMP-2. DL-homocysteine and NMDA effects were prevented by VSMC
      pre-incubation with MK-801 or high L-glycine concentrations. CONCLUSIONS: In
      human VSMC homocysteine-at concentrations associated with increased
      cardiovascular risk- activates MAPK and PI3-K pathways and MMP-2 synthesis and
      secretion through NMDA receptor, a potential mechanism involved in intracellular
      signaling in response to homocysteine in VSMC.

PMID- 19766295
TI  - Impact of surgeon and hospital ovarian cancer surgical case volume on in-hospital
      mortality and related short-term outcomes.
AB  - OBJECTIVE: To evaluate the impact of surgeon and hospital case volume, and other
      related variables, on short-term outcomes after surgery for ovarian cancer.
      METHODS: The Maryland Health Service Cost Review Commission database was accessed
      for ovarian cancer surgical cases including both oophorectomy and any
      staging/cytoreductive surgical procedure from 2001 to 2008. 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, extent of
      surgery, length of hospital stay, and hospital-related cost of care. RESULTS:
      Overall, 1894 primary ovarian cancer operations were performed by 352 surgeons at
      43 hospitals. After controlling for the effects of all variables, the only
      independently significant factors associated with the risk of in-hospital death
      were surgery by a high-volume surgeon and an APR-DRG mortality risk score of 4.
      Ovarian cancer surgery performed by a high-volume surgeon was associated with a
      69% reduction in the risk of in-hospital death. Surgery at a high-volume hospital
      was an independent positive predictor of a cytoreductive procedure. A
      statistically significant negative correlation was observed between surgery at a
      high-volume hospital and both length of hospital stay and hospital-related cost.
      CONCLUSIONS: After controlling for other factors, ovarian cancer surgery
      performed by a high-volume surgeon is associated with a 69% reduction in the risk
      of in-hospital death, while high-volume hospital care is associated with
      increased likelihood of cytoreduction, shorter length of stay, and lower hospital
      related cost of care.

PMID- 19766296
TI  - "Combined weekly carboplatin and paclitaxel as primary treatment of advanced
      epithelial ovarian carcinoma" Safra T, et al (Gynecol Oncol 2009; 114:215-218).

PMID- 19766297
TI  - Recommendations for appropriate sublingual immunotherapy clinical trials.
AB  - Sublingual immunotherapy is gaining widespread attention as a viable alternative
      to subcutaneous immunotherapy for the treatment of allergic rhinoconjunctivitis.
      In addition, sublingual immunotherapy has been studied in other allergic
      disorders including asthma. However, a review of published studies indicates that
      there are deficiencies and considerable heterogeneity in both design and data
      interpretation of sublingual immunotherapy studies. These deficiencies have made
      it somewhat difficult to assess the appropriate place of sublingual immunotherapy
      in guidelines for the therapy of allergic diseases. Moreover, several unpublished
      oral and sublingual immunotherapy studies in the United States failed to meet
      primary endpoints. This article reviews data from sublingual immunotherapy trials
      and makes recommendations about appropriate designs of future sublingual
      immunotherapy studies. It is hoped that these recommendations will result in more
      adequately designed sublingual immunotherapy trials to facilitate the appropriate
      placement of this therapy to treat patients with allergic rhinoconjunctivitis and
      other allergic diseases.

PMID- 19766298
TI  - The influence of cryopreservation and seminal plasma on the chromatin structure
      of dog spermatozoa.
AB  - It was the aim of the current study to investigate effects of seminal plasma on
      the chromatin structure of frozen-thawed canine (Canis lupus familiaris)
      spermatozoa. A total of 20 ejaculates were collected. Ejaculates were divided,
      and one half was centrifuged for removal of seminal plasma (c) while the other
      was left uncentrifuged (nc) before cryopreservation. This was performed according
      to the Uppsala system in a computerized freezing machine. Before freezing (bf)
      and after thawing (at), samples were investigated for motility (M), viability
      (CASA), and chromatin status (sperm chromatin structure assay; SCSA). Before
      freezing, the average DFI% and the SD-DFI from 20 nc ejaculates were 1.7+/-4.0%
      and 18.6+/-1.2, respectively. After thawing, all motility parameters decreased
      and were significantly lower in centrifuged than in noncentrifuged samples,
      whereas the percentage of morphologically abnormal spermatozoa (Morph) was
      significantly higher (nc: M bf, 84.1+/-20.6%; M at, 51.9+/-15%; c: M bf, 84.1+/
      20.6%; M at, 43.3+/-22.2%; Morph nc: 28.3+/-7.8% vs. c: 31.0+/-9.8%).
      Furthermore, only in c samples did the DFI increase within 6h after thawing (DFI
      c: bf, 41.8+/-1.5%; 6h at, 45.4+/-6.6%; P<0.01). The SD-DFI as well as the DFI%
      increased within 3h of storage in both groups (SD-DFI nc: bf, 18.6+/-1.2%; 3h at,
      25.8+/-5.4%; DFI% nc: bf, 1.1+/-4.0%; 3h at, 6.1+/-12.9%; P<0.05). For both
      parameters, there was no significant difference between c and nc samples at any
      time investigated. In conclusion, centrifugation of semen samples before freezing
      decreased postthaw motility and increased the percentage of morphologically
      abnormal spermatozoa as well as the degree of sperm chromatin denaturation over
      time. Centrifugation of canine ejaculates before cryopreservation can therefore
      no longer be recommended.

PMID- 19766299
TI  - Optimization of the cryopreservation of African clawed frog (Xenopus laevis)
      sperm.
AB  - Cryopreservation of testicular sperm in the African clawed frog, Xenopus laevis,
      was tested using three penetrating cryoprotectants (DMSO, methanol, and glycerol)
      and three semen diluents (300 mmol/L glucose, 300 mmol/L sucrose, and a motility
      inhibiting saline [MIS] solution [150 mmol/L NaCl, 3 mmol/L KCL, 1 mmol/L
      Mg(2)SO(4), 1 mmol/L CaCl(2), and 20 mmol/L Tris, pH 8.0]). Three freezing rates
      and four thawing rates were also tested, and the best freezing/thawing conditions
      have been determined. The responses of sperm motility, viability, and fertility
      were assessed. Incubation of the sperm macerates with penetrating cryoprotectants
      showed that DMSO was the least toxic and methanol the most toxic. Semen in
      cryodiluents frozen 10 cm above the surface of liquid nitrogen (freezing rate of
      20 to 25 degrees C/min) and thawed at room temperature for 40 sec had
      significantly higher percentages of motile and viable sperm than that of semen
      frozen 5 cm or 8 cm above the surface of liquid nitrogen and thawed at 5, 25, or
      30 degrees C for 10, 15, or 60 sec, respectively. Sperm frozen in MIS containing
      5% DMSO had a higher hatching rate than that of sperm frozen in sucrose and
      glucose diluents containing 5% or 10% DMSO and in MIS containing 10% DMSO.
      Addition of 73 mmol/L sucrose to the sperm extender MIS+5% DMSO could improve the
      postthaw sperm motility and fertility. In conclusion, dilution of collected sperm
      in MIS solution (to have a final concentration of 6.5 x 10(6) to 8 x 10(6)/mL)
      containing 5% DMSO and 73 mmol/L sucrose, freezing in a vapor of liquid nitrogen
      at 10 cm above the surface, and thawing at room temperature for 40 sec was the
      best cryopreservation protocol. This protocol gave 70% hatching rate, 80%
      motility rate, and 75% viability rate of fresh hormonally induced sperm.

PMID- 19766300
TI  - Influence of air-abrasion on zirconia ceramic bonding using an adhesive composite
      resin.
AB  - OBJECTIVES: Air-abrasion as bonding conditioning method for zirconia ceramic
      might compromise the mechanical strength of zirconia restorations. The purpose of
      this study was to evaluate the influence of surface conditioning parameters,
      i.e., air-abrasion with reduced pressure or no air-abrasion and priming with
      adhesive primers on the long-term resin bond strength to zirconia ceramic.
      METHODS: Zirconia ceramic disks were polished with 600 grit abrasive paper.
      Plexiglas tubes filled with composite resin were bonded with RelyX Unicem luting
      composite resin to the conditioned zirconia disks. Three surface conditions
      (unconditioned, air-born particle abrasion at 0.05 or 0.25 MPa) and four priming
      conditions (no priming, priming with Metal/Zirconia Primer, priming with Alloy
      Primer, priming with Clearfil Ceramic Primer) were tested. Sixteen specimens of
      each combination were bonded. Subgroups of eight bonded samples were stored in
      water either for 3 days or 150 days with 37,500 thermocycling. Tensile bond
      strengths (TBSs) were determined with a universal testing machine at a crosshead
      speed of 2mm/min. RESULTS: Without priming, RelyX Unicem showed durable bond
      strength to 0.25 MPa airborne-particle abraded ceramic. When combined with 10
      methacryloyloxy-decyl dihydrogenphosphate containing primers, air-abrasion
      resulted in a durable TBS to zirconia ceramic even at a reduced abrasion
      pressure. However, combined with Metal/Zirconia Primer air-abrasion did not
      provide a durable TBS to zirconia ceramic. SIGNIFICANCE: Using a self-adhesive
      luting resin composite (RelyX Unicem), air-abrasion at 0.25 MPa or the
      combination of low pressure air-abrasion and priming with MDP-containing primers
      seems to be useful to achieve durable long-term bonding to zirconia ceramic.

PMID- 19766301
TI  - Variations in collagen fibrils network structure and surface dehydration of acid
      demineralized intertubular dentin: effect of dentin depth and air-exposure time.
AB  - OBJECTIVE: The aim was to characterize the variations in the structure and
      surface dehydration of acid demineralized intertubular dentin collagen network
      with the variations in dentin depth and time of air-exposure (3, 6, 9 and 12
      min). In addition, to study the effect of these variations on the tensile bond
      strength (TBS) to dentin. METHODS: Phosphoric acid demineralized superficial and
      deep dentin specimens were prepared. The structure of the dentin collagen network
      was characterized by AFM. The surface dehydration was characterized by probing
      the nano-scale adhesion force (F(ad)) between AFM tip and intertubular dentin
      surface as a new experimental approach. The TBS to dentin was evaluated using an
      alcohol-based dentin self-priming adhesive. RESULTS: AFM images revealed a
      demineralized open collagen network structure in both of superficial and deep
      dentin at 3 and 6 min of air-exposure. However, at 9 min, superficial dentin
      showed more collapsed network structure compared to deep dentin that partially
      preserved the open network structure. Total collapsed structure was found at 12
      min for both of superficial and deep dentin. The value of the F(ad) is decreased
      with increasing the time of air-exposure and is increased with dentin depth at
      the same time of air-exposure. The TBS was higher for superficial dentin at 3 and
      6 min, however, no difference was found at 9 and 12 min. SIGNIFICANCE: The
      ability of the demineralized dentin collagen network to resist air-dehydration
      and to preserve the integrity of open network structure with the increase in air
      exposure time is increased with dentin depth. Although superficial dentin
      achieves higher bond strength values, the difference in the bond strength is
      decreased by increasing the time of air-exposure. The AFM probed F(ad) showed to
      be sensitive approach to characterize surface dehydration, however, further
      researches are recommended regarding the validity of such approach.

PMID- 19766302
TI  - Effectiveness of an attachment-focused manualized intervention for parents of
      teens at risk for aggressive behaviour: The Connect Program.
AB  - Aggressive, violent and antisocial behaviour in children and adolescents is a
      growing concern across the globe. Targeting parent-teen relationships is critical
      in reducing problem behaviour. 'Connect' is a manualized ten-week program for
      parents or alternative caregivers of at-risk teens that focuses on the building
      blocks of secure attachment: parental sensitivity, cooperation, reflective
      capacity, and effective dyadic affect regulation. Through didactic and
      experiential activities, parents develop the competence necessary to identify,
      understand and respond to the needs of their teen in a manner that provides
      structure and safety while safeguarding the quality of the parent-teen
      relationship. In Study 1, twenty parents reported significant increases in
      perceived parenting satisfaction and efficacy and reductions in adolescents'
      aggression, antisocial behaviour and other mental health problems following
      completion of Connect as compared to a waitlist control period. These effects
      were sustained and additional small effects were noted in decreases in conduct
      problems, depression and anxiety at a 12-month follow-up. The program was then
      transported to 17 communities serving 309 parents through standardized training
      and supervision of group leaders. Study 2 summarizes significant pre- to post
      treatment reductions in teen externalizing and internalizing problems; enhanced
      social functioning; and improvements in affect regulation. Parents also reported
      significant increases in parenting satisfaction and perceived efficacy and
      reductions in caregiver burden.

PMID- 19766303
TI  - Phytoplankton and bacterial alkaline phosphatase activity in the northern
      Adriatic Sea.
AB  - The importance of bacterial, phytoplankton and dissolved alkaline phosphatase
      activity (APA) in the northern Adriatic was investigated during 2006. In surface
      waters total APA increased from early spring (0.07-0.08 micromol l(-1) h(-1)) to
      late spring (up to 4.64 micromol l(-1) h(-1)) and remained relatively high during
      the summer (0.46-0.71 micromol l(-1) h(-1)), due to an increase in specific
      phytoplankton (up to 30 nmol microg C(-1) h(-1)) and bacterial APA (up to 17.11
      nmol microg C(-1) h(-1)). Activity of free enzymes was not important. During late
      spring and summer both communities exploited dissolved organic phosphorus
      although, taking into account biomass, phytoplankton activity usually dominated
      over bacterial activity. In autumn an extra P supply from deeper waters
      drastically reduced phytoplankton APA, though not bacterial APA, in upper waters.
      Probably in these months bacteria that were degrading phytoplankton produced
      organic matter were P limited. In deeper waters APA was low and mainly due to the
      activity of free enzymes.

PMID- 19766304
TI  - The use of size-defined DNA-functionalized calcium phosphate nanoparticles to
      minimise intracellular calcium disturbance during transfection.
AB  - Calcium phosphate-based transfection methods are frequently used to transfer DNA
      into living cells. However, it has so far not been studied in detail to what
      extend the different transfection methods lead to a net calcium uptake. Upon
      subsequent resolution of the calcium phosphate, intracellular free ionic calcium
      surges could result, inducing as side effect various physiological responses that
      may finally result in cell death. Here we investigated the overall calcium uptake
      by the human bladder carcinoma cell line T24 during the standard calcium
      phosphate transfection method and also during transfection with custom-made
      calcium phosphate/DNA nanoparticles by isotope labelling with (45)calcium.
      (45)Calcium uptake was strongly increased after 7h of standard calcium phosphate
      transfection but not if the transfection was performed with calcium phosphate
      nanoparticles. Time lapse imaging microscopy using the calcium-sensitive dye Fura
      2 revealed large transient increases of the intracellular free calcium level
      during the standard calcium phosphate transfection but not if calcium phosphate
      nanoparticles were used. Consistently, the viability of cells transfected by
      calcium phosphate/DNA nanoparticles was not changed, in remarkable contrast to
      the standard method where considerable cell death occurred.

PMID- 19766305
TI  - Engulfing tumors with synthetic extracellular matrices for cancer immunotherapy.
AB  - Local immunotherapies are under investigation for the treatment of unresectable
      tumors and sites of solid tumor resection to prevent local recurrence. Successful
      local therapy could also theoretically elicit systemic immune responses against
      cancer. Here we explored the delivery of therapeutic dendritic cells (DCs),
      cytokines, or other immunostimulatory factors to tumors via the use of 'self
      gelling' hydrogels based on the polysaccharide alginate, injected peritumorally
      around established melanoma lesions. Peritumoral injection of alginate matrices
      loaded with DCs and/or an interleukin-15 superagonist (IL-15SA) around 14-day
      established ova-expressing B16F0 murine melanoma tumors promoted immune cell
      accumulation in the peritumoral matrix, and matrix infiltration correlated with
      tumor infiltration by leukocytes. Single injections of IL-15SA-carrying gels
      concentrated the cytokine in the tumor site approximately 40-fold compared to
      systemic injection and enabled a majority of treated animals to suppress tumor
      growth for a week or more. Further, we found that single injections of alginate
      matrices loaded with IL-15SA and the Toll-like receptor ligand CpG or two
      injections of gels carrying IL-15SA alone could elicit comparable anti-tumor
      activity without the need for exogenous DCs. Thus, injectable alginate gels offer
      an attractive platform for local tumor immunotherapy, and facilitate
      combinatorial treatments designed to promote immune responses locally at a tumor
      site while limiting systemic exposure to potent immunomodulatory factors.

PMID- 19766306
TI  - Influence of micro-well biomimetic topography on intestinal epithelial Caco-2
      cell phenotype.
AB  - A microfabrication approach was utilized to create topographic analogs of
      intestinal crypts on a polymer substrate. It was hypothesized that biomimetic
      crypt-like micro-architecture may induce changes in small intestinal cell (i.e.
      Caco-2 cell) phenotype. A test pattern of micro-well features with similar
      dimensions (50, 100, and 500 microm diameter, 50 microm spacing, 120 microm in
      depth) to the crypt structures found in native basal lamina was produced in the
      surface of a poly(dimethylsiloxane) (PDMS) substrate. PDMS surfaces were coated
      with fibronectin, seeded with intestinal-epithelial-cell-like Caco-2 cells, and
      cultured up to fourteen days. The cells were able to crawl along the steep side
      walls and migrated from the bottom to the top of the well structures, completely
      covering the surface by 4-5 days in culture. The topography of the PDMS
      substrates influenced cell spreading after seeding; cells spread faster and in a
      more uniform fashion on flat surfaces than on those with micro-well structures,
      where cell protrusions extending to micro-well side walls was evident. Substrate
      topography also affected cell metabolic activity and differentiation; cells had
      higher mitochondrial activity but lower alkaline phosphatase activity at early
      time points in culture (2-3 days post-seeding) when seeded on micro-well
      patterned PDMS substrates compared to flat substrates. These results emphasize
      the importance of topographical design properties of a scaffolds used for tissue
      engineered intestine.

PMID- 19766307
TI  - The kinetics of thermal instability in nanocrystalline silver and the effect of
      heat treatment on the antibacterial activity of nanocrystalline silver dressings.
AB  - The kinetics of nanocrystalline silver dressing heat treatment was investigated
      via isothermal heat treatments at 90 degrees C, 100 degrees C, and 110 degrees C
      lasting 2-50h. Bactericidal efficacy of the dressings was measured via log
      reductions, while bacteriostatic longevity was determined via plate-to-plate
      transfer corrected zones of inhibition. Morphological evolution of the dressing
      was studied by X-ray diffraction, scanning electron microscopy, and X-ray
      photoelectron spectroscopy, while changes in heat flow were measured by
      differential scanning calorimetry. Increasing temperature increased the rate at
      which dressing bactericidal activity and bacteriostatic longevity decreased. Once
      changes in dressing properties began, they occurred nonlinearly with time. The
      earliest biological, chemical, and physical indicators of altered dressing
      properties were loss of bacteriostatic longevity, silver-oxygen bonds, and fine
      features, respectively. An early change in heat flow appeared to be responsible
      for these indicators, while a later change corresponded to rapid grain growth
      occurring after a critical crystallite size (approximately 30 nm) was reached.
      The grain growth exponent was determined to be 2.8 for temperatures of 100-110
      degrees C, with an activation energy of 177 kJ/mol, suggesting that normal grain
      growth occurred, with volume and/or grain boundary diffusion as the dominant
      forms of diffusion. The thermal instability of nanocrystalline silver should be
      accounted for during production, storage, and use of dressings. The properties
      required for nanosilver antimicrobial efficacy demonstrated in this study, as
      well as its thermal instability, should be taken into consideration for the
      development of nanosilver products in the future.

PMID- 19766308
TI  - The isolation and characterization of a novel telomerase immortalized first
      trimester trophoblast cell line, Swan 71.
AB  - Studies using first trimester trophoblast cells may be limited by the inability
      to obtain patient samples and/or adequate cell numbers. First trimester
      trophoblast cell lines have been generated by SV40 transformation or similar
      methods, however, this approach is known to induce phenotypic and karyotypic
      abnormalities. The introduction of telomerase has been proposed to be a viable
      alternative for the immortalization of primary human cells. To investigate
      whether telomerase-induced immortalization might be a more feasible approach for
      the generation of first trimester trophoblast cell lines, we isolated primary
      trophoblast cells from a 7-week normal placenta and infected the cells with human
      telomerase reverse transcriptase (hTERT), the catalytic subunit of telomerase.
      Although this hTERT-infected first trimester trophoblast cell line, which we have
      named Swan 71, has been propagated for more than 100 passages, it still has
      attributes that are characteristic of primary first trimester trophoblast cells.
      The Swan 71 cells are positive for the expression of cytokeratin 7, vimentin and
      HLA-G, but do not express CD45, CD68 or the Fibroblast Specific Antigen (FSA),
      CD90/Thy-1. In addition, we also demonstrated that the Swan 71 cells secrete
      fetal fibronectin (FFN) as well as low levels of human Chorionic Gonadotrophin
      (hCG). Moreover, the Swan 71 cells exhibit a cytokine and growth factor profile
      that is similar to primary trophoblast cells and are resistant to Fas, but not
      TNF-alpha-induced apoptosis. This suggests that the Swan 71 cells may represent a
      valuable model for future in vitro trophoblast studies.

PMID- 19766309
TI  - Is the diagnosis of physical abuse changed when Child Protective Services
      consults a Child Abuse Pediatrics subspecialty group as a second opinion?
AB  - OBJECTIVES: To characterize the changes regarding the diagnosis of physical abuse
      provided to Child Protective Services (CPS) when CPS asks a Child Abuse
      Pediatrics (CAP) specialty group for a second opinion and works in concert with
      that CAP group. METHODS: Subjects were reported to CPS for suspected physical
      abuse and were first evaluated by a physician without specialized training in
      Child Abuse Pediatrics (non-CAP physician). Subjects were then referred to the
      area's only Child Abuse Pediatrics (CAP physician) group, located in a large
      metropolitan pediatrics center in the United States, for further evaluation. The
      diagnoses regarding abuse provided by CAP physicians working in concert with CPS
      were compared to those provided to CPS by other physicians. RESULTS: Two hundred
      consecutive patients were included in the study. In 85 (42.5%) cases, non-CAP
      physicians did not provide a diagnosis regarding abuse, despite initiating the
      abuse report to CPS or being asked by CPS to evaluate the child for physical
      abuse. Of the remaining 115 cases, the diagnosis regarding abuse differed between
      non-CAP physicians and CAP physicians working in concert with CPS in 49 cases
      (42.6%; kappa=.14; 95% CI, -.02, .29). In 40 of the 49 cases (81.6%), CAP
      assessments indicated less concern for abuse when compared to non-CAP
      assessments. Differences in diagnosis were three times more likely in children
      from a nonurban location (OR 3.24; 95% CI, 1.01, 11.36). CONCLUSIONS: In many
      cases of possible child physical abuse, non-CAP providers do not provide CPS with
      a diagnosis regarding abuse despite initiating the abuse investigation or being
      consulted by CPS for an abuse evaluation. CPS consultation with a CAP specialty
      group as a second opinion, along with continued information exchange and team
      collaboration, frequently results in a different diagnosis regarding abuse. Non
      CAP providers may not have time, resources, or expertise to provide CPS with
      appropriate abuse evaluations in all cases. PRACTICE IMPLICATIONS: Though non-CAP
      providers may appropriately evaluate many cases of physical abuse, the diagnosis
      regarding abuse provided to CPS may be changed in some cases when CAP physicians
      are consulted and actively collaborate with CPS investigators. Availability of
      Child Abuse Pediatrics subspecialty services to investigators is warranted.

PMID- 19766310
TI  - Exploratory assessments of child abuse: children's responses to interviewer's
      questions across multiple interview sessions.
AB  - OBJECTIVE: The present study extends field research on interviews with young
      children suspected of having been abused by examining multiple assessment
      interviews designed to be inquisitory and exploratory, rather than formal
      evidential or forensic interviews. METHODS: Sixty-six interviews with 24 children
      between the ages of 3 and 6 years who were undergoing an assessment for suspected
      child abuse were examined. Each child was interviewed 2, 3, or 4 times. The
      interviewer's questions were categorized in terms of openness (open, closed or
      choice), in terms of the degree of interviewer input (free recall, direct,
      leading, suggestive), and for topic (whether the question was abuse-specific or
      nonabuse-related). Children's on-task responses were coded for amount of
      information (number of clauses) reported in relation to each question type and
      topic, and off-task responses were categorized as either ignoring the question or
      a diverted response. RESULTS: Children provided a response to most questions,
      independent of question type or topic and typically responded with one or two
      simple clauses. Some children disclosed abuse in response to open-ended
      questions; generally, however, failure to respond to a question was more likely
      for abuse-specific than for nonabuse-related questions. CONCLUSION: The findings
      are discussed in terms of the growing literature on interviewing children about
      suspected abuse, particularly in interviews conducted over multiple sessions.
      PRACTICE IMPLICATIONS: Assessment of suspected child abuse may involve more than
      a single investigative interview. Research examining children's responses to
      questioning over multiple interviews (or single interviews conducted over
      multiple sessions) is necessary for the development of best practise guidelines
      for the assessment of abuse.

PMID- 19766311
TI  - Endovascular treatment of anterior choroidal artery aneurysms.
AB  - INTRODUCTION: Endovascular treatment (EVT) of anterior choroidal artery aneurysms
      (AChAA) may be challenging because of the close relationship with the parent
      artery. The aim of this study was to report our experience with EVT of AChAA.
      METHODS: A retrospective review of our prospectively maintained database
      identified all AChAA treated by embolization. The clinical charts, procedural
      data and angiographic results were reviewed. RESULTS: From April 2004-August
      2008, 11 patients were identified. Five patients presented with a subarachnoid
      hemorrhage (SAH) and six patients were asymptomatic. Aneurysms size varied from
      two to 13 mm (mean size=3.6 mm) and nine had an unfavourable neck/sac ratio
      (>or=0.7). The anterior choroidal artery was arising from the sac (n=6) or from
      the neck (n=5). Endovascular treatment consisted of balloon-assisted coiling
      (n=8), coiling (n=2) and stent-assisted coiling (n=1). No procedural complication
      occurred and all patients had an excellent outcome except one patient who died
      because of severe vasospasm 8 days after an uneventful EVT. Immediate
      angiographic control showed six complete occlusions, one neck remnant and four
      incomplete occlusions. Follow-up controls (mean=18 months) were obtained in eight
      patients and showed five stable occlusions and three further thrombosis achieving
      complete occlusion. CONCLUSION: EVT of AChAA is associated with very good
      clinical and long-term anatomical results. Because of their small size,
      unfavourable neck/sac ratio and close relationship with the parent artery, EVT
      frequently requires the use of adjunctive techniques such as balloon or stent
      assisted coiling.

PMID- 19766312
TI  - Traumatic intracranial dissection: mural hematoma on high-resolution MRI.

PMID- 19766314
TI  - [Cerebral amyloid angiopathy: a forgotten cause of sub-arachnoid hemorrhage].

PMID- 19766315
TI  - Characteristics of traumatic globe rupture after keratoplasty.
AB  - OBJECTIVE: To analyze risk factors of traumatic wound rupture after penetrating
      keratoplasty (PKP) or deep anterior lamellar keratoplasty (DALK). DESIGN:
      Retrospective case series. PARTICIPANTS: A total of 1962 consecutive cases were
      included. METHODS: A review of consecutive patients undergoing either PKP (1776
      eyes) or DALK (186 eyes) at 1 regional center between 1998 and 2006 was carried
      out to determine the incidence of traumatic globe rupture after keratoplasty.
      Ophthalmic and demographic factors were analyzed. A comparison with previous
      literature was performed. MAIN OUTCOME AND MEASURES: Incidence, causes, and final
      visual acuity. RESULTS: Of 43 eyes with globe rupture during this period, 36
      received keratoplasty during this study period. The incidence of globe rupture
      after keratoplasty was 1.8% (36/1962). These 36 cases consisted of 35 of the 1776
      eyes receiving PKP (2.0%) and 1 of the 186 eyes receiving DALK (0.5%). Globe
      rupture occurred 61.6+/-50.0 months (mean +/- standard deviation) after
      keratoplasty in 43 cases. The major cause of trauma was a fall in elderly
      patients (73.2+/-8.4 years, 17 eyes), with lens damage occurring in all such
      cases. Although 15 eyes (34.9%) had a visual acuity of 20/200 or better at final
      follow-up, eyes showing lens damage were associated with poorer visual acuity
      than eyes with no lens damage (P<0.01). CONCLUSIONS: Wound weakness persisted for
      a long period after keratoplasty. A fall was observed frequently in elderly
      patients and resulted in poor visual outcome. Globe rupture associated with lens
      injury could be the predictor for future visual outcome.

PMID- 19766316
TI  - Ocular manifestation in treated multibacillary Hansen's disease.
AB  - PURPOSE: To report the prevalence of ocular morbidity in patients with treated
      multibacillary Hansen's disease (HD) using modern ophthalmic diagnostic
      techniques in a rural community endemic for HD. DESIGN: Cross-sectional,
      observation study. PARTICIPANTS: All patients with multibacillary HD who had
      completed their multidrug therapy and who resided in 4 defined geographical areas
      in Vellore, Tamil Nadu, India. METHODS: All participants underwent a complete eye
      examination that included slit-lamp examination, esthesiometry, gonioscopy,
      applanation tonometry, and dilated fundus examination, including a
      stereobiomicroscopic examination of the fundus at an ophthalmic center set up for
      that purpose. Glaucoma suspects underwent automated perimetry using a Humphrey
      Field Analyzer (Humphrey Instruments, San Leandro, CA). MAIN OUTCOME MEASURES:
      The prevalence of various ocular disease parameters were reported as mean value
      with 95% confidence interval. The difference of disease prevalence between
      various leprosy groups was compared using an unpaired t test. The association
      between eye symptoms and potentially sight-threatening complications was analyzed
      using the chi-square test. RESULTS: Three hundred eighty-six of the 446 patients
      with multibacillary HD residing in the defined areas were evaluated. Four
      patients (1.04%; 95% confidence interval [CI], 0.0%-2.0%) were bilaterally blind;
      33 (8.55%; 95% CI, 5.8%-11.3%) had unilateral blindness. Mean intraocular
      pressure was 12 mmHg (standard deviation, 4.1 mmHg), and prevalence of glaucoma
      was 3.6% (95% CI, 1.8%-5.5%). Potentially sight-threatening (PST) pathologic
      features (corneal anesthesia, lagophthalmos, uveitis, scleritis, and advanced
      glaucoma) were present in 10.4% (95% CI, 7.4%-13.4%) of patients. Significant
      cataracts occurred 3 times more frequently in those with polar lepromatous
      leprosy. The odds ratio for PST pathology in the presence of patient-reported
      symptoms (pain, redness, inability to close eye, burning, and irritation) was 2.9
      (95% CI, 1.34-6.26). CONCLUSIONS: Patients who have completed treatment for
      multibacillary HD continue to have significant ocular morbidity. A history of
      specific eye symptoms can be the basis for referral by field staff.

PMID- 19766317
TI  - Insights into advanced retinopathy of prematurity using handheld spectral domain
      optical coherence tomography imaging.
AB  - PURPOSE: To elucidate the subclinical anatomy of retinopathy of prematurity (ROP)
      using spectral domain optical coherence tomography (SD OCT). DESIGN: Prospective,
      observational case series. PARTICIPANTS: Three low-birth-weight, severely
      premature infants. METHODS: Clinical examination was performed using a portable
      slit lamp and indirect ophthalmoscope. Imaging was performed by using a handheld
      SD OCT device and Retcam (Clarity Medical Systems, Pleasanton, CA) or video
      indirect recording. Spectral domain optical coherence tomography imaging was
      conducted without sedation at the bedside in the neonatal intensive care unit on
      1 patient. The other 2 patients had an examination under anesthesia with SD OCT
      imaging in the operating room. MAIN OUTCOME MEASURES: In vivo determination of
      vitreoretinal morphology, anatomy, and pathology by clinical examination,
      imaging, and SD OCT. RESULTS: Linear and volumetric imaging was achieved with the
      handheld system in infant eyes despite tunica vasculosa lentis and vitreous
      bands. Imaging was not possible in eyes with notable vitreous hemorrhage.
      Analysis of SD OCT images revealed preretinal structures (ranging from 409 to
      2700 microm in width and 212 to 440 microm in height), retinoschisis, and retinal
      detachment in the posterior pole of patients with advanced ROP. Both the
      retinoschisis and the preretinal structures were not identified on conventional
      examination or imaging by expert pediatric ophthalmologists. The preretinal
      structures varied in location and size, and may represent preretinal
      fibrovascular proliferation. Some were found in close proximity to blood vessels,
      whereas others were near the optic nerve. CONCLUSIONS: Handheld SD OCT imaging
      can be performed on the sedated or nonsedated neonate and provides valuable
      subclinical anatomic information. This novel imaging modality can reveal the
      location and extent of posterior ROP pathology not evident on standard
      examination. This could affect future clinical decision-making if studies
      validate a management strategy based on findings from this imaging technique.

PMID- 19766318
TI  - Sentinel lymph node biopsy for ocular adnexal melanoma: experience in 30
      patients.
AB  - PURPOSE: To report the findings on sentinel lymph node biopsy (SLNB) in 30
      patients with ocular adnexal (conjunctival or eyelid) melanomas. DESIGN:
      Prospective nonrandomized clinical trial. PARTICIPANTS: Thirty patients with
      diagnosis of eyelid or conjunctival melanoma. METHODS: All patients with ocular
      adnexal melanoma who underwent SLNB at The University of Texas MD Anderson Cancer
      Center between December 2000 and July 2008 are the subject of this report.
      Sentinel lymph node biopsy was performed as previously described by our group,
      and patients were prospectively followed up. MAIN OUTCOME MEASURES: Findings on
      preoperative lymphoscintigraphy, SLNB, histopathologic examination of the primary
      tumor and sentinel lymph nodes (SNL), and nodal recurrence after SLNB. RESULTS:
      Tumor sites were as follows: bulbar conjunctiva only, 14 patients; palpebral
      conjunctiva only, 8 patients; both bulbar and palpebral conjunctiva, 4 patients;
      and eyelid skin only, 4 patients. At least 1 SLN was identified in all patients.
      The median number of SLNs removed was 2 (range, 1-5). The most common basin
      sampled was the intraparotid (16 patients), followed by submandibular (level I)
      (11 patients), preauricular (9 patients), and superior cervical (level II) (6
      patients). Five patients had SLN metastasis. Among the 25 patients with negative
      SLNB findings, there were 2 false-negative events. There were no false-negative
      events among patients treated during the last 4.5 years of the study. The mean
      Breslow thickness was 2.57 mm (range, 0.62-12 mm) among patients with negative
      SLNB and 4.86 mm (range, 2.0-7.2 mm) among patients with positive SLNB findings
      (P = 0.055). Ulceration was present in 11 patients (39%): 4 (80%) of 5 patients
      with positive SLNB and 7 (28%) of 25 with negative SLNB, including both patients
      with false-negative results. The median time from SLNB to last contact was 2
      years (range, 10 months to 6 years). CONCLUSIONS: Sentinel lymph node biopsy is
      effective for identifying nodal micrometastasis in patients with ocular adnexal
      melanoma and provides important prognostic information. The false-negative event
      rate in our series improved in the last 4 years, most likely because of a better
      technique and better patient selection for SLNB. We recommend consideration of
      SLNB for patients with intermediate-thickness ocular adnexal melanoma and those
      with ulceration.

PMID- 19766319
TI  - Glyphosate complexation to aluminium(III). An equilibrium and structural study in
      solution using potentiometry, multinuclear NMR, ATR-FTIR, ESI-MS and DFT
      calculations.
AB  - The stoichiometries and stability constants of a series of Al(3+)-N
      phosponomethyl glycine (PMG/H(3)L) complexes have been determined in acidic
      aqueous solution using a combination of precise potentiometric titration data,
      quantitative (27)Al and (31)P NMR spectra, ATR-FTIR spectrum and ESI-MS
      measurements (0.6M NaCl, 25 degrees C). Besides the mononuclear AlH(2)L(2+),
      Al(H(2)L)(HL), Al(HL)(2)(-) and Al(HL)L(2-), dimeric Al(2)(HL)L(+) and trinuclear
      Al(3)H(5)L(4)(2+) complexes have been postulated. (1)H and (31)P NMR data show
      that different isomers co-exist in solution and the isomerization reactions are
      slow on the (31)P NMR time scale. The geometries of monomeric and dimeric
      complexes likely double hydroxo bridged and double phosphonate bridged isomers
      have been optimized using DFT ab initio calculations starting from rational
      structural proposals. Energy calculations using the PCM solvation method also
      support the co-existence of isomers in solutions.

PMID- 19766320
TI  - Complex formation of quercetin with lanthanum enhances binding to plant viral
      satellite double stranded RNA.
AB  - Due to the broad spectrum of biological activities of flavonoids, their target
      molecules in the cell are intensively studied. We examined the interactions of
      the flavonoid quercetin (Q) and its lanthanum complex (QLa(3+)) with very
      recently isolated plant viral satellite (sat) dsRNA. Comparison of the cumulative
      binding affinity and the estimated intercalative binding constant pointed towards
      an additional binding mode of quercetin to exclusively viral dsRNA, which is not
      recorded for synthetic dsRNAs. The QLa(3+) showed significantly higher affinity
      toward viral dsRNA than Q and La(3+) alone, most likely as the consequence of
      quercetin intercalation accompanied by additional electrostatic interaction of
      La(3+) with the negatively charged viral RNA backbone.

PMID- 19766321
TI  - Gray matter reduction of the superior temporal gyrus in patients with established
      bipolar I disorder.
AB  - BACKGROUND: Functional abnormalities of the superior temporal gyrus (STG) have
      been implicated in the pathophysiology of bipolar disorder, but magnetic
      resonance imaging (MRI) studies of this region have yielded inconsistent
      findings. METHOD: We used MRI to examine the volumes of the STG and its gray
      matter subregions [planum polare (PP), Heschl gyrus (HG), planum temporale (PT),
      and lateral STG (rostral and caudal regions)] in 26 patients with established
      bipolar I disorder (8 males and 18 females, mean age=38.4 years) and 24 age and
      gender-matched healthy controls (7 males and 17 females, mean age=38.7 years).
      RESULTS: Bipolar patients had significantly smaller volumes of the PT and caudal
      STG compared with controls in the left hemisphere. The STG white matter volume
      did not differ between the groups. There was no association between the STG
      volume and number of manic/depressive episodes, family history, or clinical
      subtype (i.e., psychotic and nonpsychotic), but daily dosage of lithium treatment
      at the time of scanning was positively correlated with right PP and right rostral
      STG volumes. LIMITATIONS: Entire clinical data (e.g., lifetime medication,
      symptomatology) were not available. CONCLUSIONS: These findings implicate a role
      for the STG gray matter, especially its left posterior regions, in the
      neurobiology of bipolar disorder. Our findings may also support the notion of
      lithium-induced gray matter expansion.

PMID- 19766322
TI  - Cloning and expression of activation induced cytidine deaminase from Bos taurus.
AB  - Activation induced cytidine deaminase is an enzyme crucial to somatic
      hypermutation and gene conversion, processes that are essential for the
      diversification of Ig V genes. The bovine Ig repertoire appears to be diversified
      by mechanisms that are significantly different to those that operate in humans
      and mice. This study set out to test the hypothesis that differences in the
      organization, coding sequence, expression or genomic location of the bovine AICDA
      gene enables the encoded enzyme to catalyse the unusual Ig diversification
      mechanism seen in cattle as well as conventional antigen-driven mutation.
      Characterization of bovine AICDA excluded the first two possibilities. AICDA
      expression was detected in lymphoid tissues from neonatal and older cattle, but
      AICDA cDNA could not be detected in muscle tissue. The pattern of gene expression
      did not therefore differ from that in other vertebrates. The AICDA cDNA was
      cloned and expressed successfully in Escherichia coli generating a phenotype
      consistent with the mutating action of this deaminase. Using a whole genome
      radiation hybrid panel, bovine AICDA was mapped to a region of bovine chromosome
      5 syntenic with the location of human AICDA on chromosome 12. We conclude that
      the unusual nature of Ig diversification in cattle is unlikely to be attributable
      to the structure, sequence, activity or genomic location of bovine AICDA.

PMID- 19766323
TI  - Differential modulation of lipopolysaccharide-induced expression of inflammatory
      genes in equine monocytes through activation of adenosine A2A receptors.
AB  - Adenosine is an endogenous nucleoside that has potent receptor-mediated
      immunomodulatory effects on macrophage/monocyte function. In this study, we
      determined the effects of an adenosine A(2A) receptor agonist, ATL313, on the
      expression of mRNAs for four pro-inflammatory mediators, IL-1beta, IL-8, COX-2,
      and TNF-alpha, and the mRNA and protein for the anti-inflammatory cytokine, IL-10
      in equine monocytes incubated with lipopolysaccharide (LPS). The results indicate
      that ATL313 significantly reduces LPS-induced expression of COX-2 and TNF-alpha,
      enhances the expression of IL-10 and IL-8, but does not alter the expression of
      IL-1beta. These effects of ATL313 were reversed by co-incubation with the
      selective adenosine A(2A) antagonist ZM241385, and were mimicked by the cAMP
      analogue dibutyryl cAMP. These differential effects of adenosine A(2A) receptor
      activation were in contrast to those obtained using the P38 MAPK inhibitor,
      SB203580, which nearly abolished all LPS-induced changes in mRNA expression as
      well as the production of TNF-alpha protein. These findings, which indicate that
      adenosine A(2A) receptor activation modulates the transcription of several, but
      not all, pro-inflammatory mediators and exerts a synergistic effect on the
      induction of at least one anti-inflammatory cytokine, suggest that selective
      adenosine A(2A) agonists may reduce the early pro-inflammatory effects of
      endotoxemia in horses.

PMID- 19766324
TI  - Phagocytosis in pup and adult harbour, grey and harp seals.
AB  - Knowledge on pinniped immunology is still in its infancy. For instance, age
      related and developmental aspects of the immune system in pinnipeds need to be
      better described. The present study examined the phagocytic activity and
      efficiency of harbour, grey and harp seal leukocytes. In the first part of the
      study, peripheral blood was collected from captive female harbour seals of
      various ages. Data showed an age-related decrease in phagocytosis in female
      harbour seals from sub-adult to adulthood. In the second part of the study,
      changes in phagocytosis were quantified during lactation in wild newborn harbour,
      grey and harp seals and in their mothers (harp and grey seals). In newborns of
      the same age, leukocytes of harbour and harp seals phagocytosed less than those
      of grey seal pups. The phagocytic activity and efficiency increased significantly
      from early to mid-lactation in newborn harbour seals, and from early to late
      lactation in newborn grey seals, which could suggest that the transfer of
      phagocytosis-promoting factor(s) in colostrum is an important feature of
      temporary protection for pups. In contrast, no changes in phagocytic activity and
      efficiency were observed in lactating females of the two seal species, harp and
      grey, examined. At late lactation, phagocytic activity in both grey and harp seal
      pups and phagocytic efficiency in grey seal pups were significantly higher than
      in their mothers. These results could reflect either the capacity of phagocytes
      of the newborn harp and grey seals to respond to pathogens. Results from this
      study suggest that the phagocytosis of the seal species examined is not fully
      developed at birth as it generally increases in pups during lactation.
      Thereafter, the phagocytic activity of seals appears to decrease throughout
      adulthood.

PMID- 19766325
TI  - Changes in T cell phenotype and activated MAPKs are correlated to impaired
      cellular responses to antigens and glucocorticoids during HTLV-I infection.
AB  - Lymphocytes of human T-lymphotropic virus type-I (HTLV-I) infected patients were
      previously found tolerant to mitogenic stimuli as well as glucocorticoid
      treatment. These data suggest that common signaling events are impaired during
      this infection. The underlying mechanisms of these phenomena may include changes
      in cellular composition, cytokine milieu and the differential activation of
      mitogen-activated protein kinases (MAPKs). We investigated the role of (i) p38
      and ERK MAPKs, (ii) lymphocyte subpopulations, (iii) and cytokines implicated in
      antigen or glucocorticoid-induced immunomodulation. Twenty-one asymptomatic
      carriers (AC), 19 patients with HTLV-I-associated myelopathy/tropical spastic
      paraparesis (HAM/TSP) and 21 healthy subjects took part in this study.
      Lymphocytes were isolated and cultured in vitro to assess lymphocyte
      proliferation and sensitivity to dexamethasone. The expression of phospho-MAPKs,
      lymphocyte subsets and cytokines were assessed by flow cytometry. Patients with
      HAM/TSP had a higher p38/ERK ratio (p<0.05) associated with a reduced response to
      mitogens (phytohaemagglutinin or PMA+ionomycin) (p<0.001) and higher sensitivity
      to dexamethasone (p<0.05). HAM/TSP patients presented increased frequency of
      activated T cells and CD8(+)CD28(-) regulatory T cells, being negatively related
      to the mitogenic response. These data suggest that multiple underlying mechanisms
      could be involved with HTLV-related changes in cellular response to mitogens and
      glucocorticoids.

PMID- 19766326
TI  - Transplanted myogenic progenitor cells express neuronal markers in the CNS and
      ameliorate disease in experimental autoimmune encephalomyelitis.
AB  - This study explores the potential of non-neural progenitor cells for CNS cell
      therapy. Muscle progenitor cells (MPCs), transplanted either intraventricularly
      or intraperitonealy, incorporated into the CNS of EAE-induced but not of naive
      mice. Some of the migrating MPCs expressed the neuronal marker beta-III-Tubulin
      and gained neuronal morphology. Co-treatment of transplanted mice with the
      immunomodulatory agent glatiramer acetate (GA, Copaxone) resulted in improved
      MPCs incorporation and differentiation towards the neuronal pathway. The
      therapeutic potential of myogenic progenitor cells was demonstrated by
      amelioration of clinical symptoms and reduced mortality in EAE mice, as well as
      by expression of IL-10, TGF-beta, and the neurotrophin-BDNF.

PMID- 19766327
TI  - Flavonoids, a prenatal prophylaxis via targeting JAK2/STAT3 signaling to oppose
      IL-6/MIA associated autism.
AB  - Maternal immune activation (MIA) can affect fetal brain development and thus
      behavior of young and adult offspring. Reports have shown that increased
      Interleukin-6 (IL-6) in the maternal serum plays a key role in altering fetal
      brain development, and may impair social behaviors in the offspring.
      Interestingly, these effects could be attenuated by blocking IL-6. The current
      study investigated the effects of luteolin, a citrus bioflavonoid, and its
      structural analog, diosmin, on IL-6 induced JAK2/STAT3 (Janus tyrosine kinase
      2/signal transducer and activator of transcription-3) phosphorylation and
      signaling as well as behavioral phenotypes of MIA offspring. Luteolin and diosmin
      inhibited neuronal JAK2/STAT3 phosphorylation both in vitro and in vivo following
      IL-6 challenge as well as significantly diminishing behavioral deficits in social
      interaction. Importantly, our results showed that diosmin (10mg/kgday) was able
      to block the STAT3 signal pathway; significantly opposing MIA-induced abnormal
      behavior and neuropathological abnormalities in MIA/adult offspring. Diosmin's
      molecular inhibition of JAK2/STAT3 pathway may underlie the attenuation of
      abnormal social interaction in IL-6/MIA adult offspring.

PMID- 19766328
TI  - Effects of interferon-beta therapy on innate and adaptive immune responses to the
      human endogenous retroviruses HERV-H and HERV-W, cytokine production, and the
      lectin complement activation pathway in multiple sclerosis.
AB  - The effects of treatment of multiple sclerosis patients with IFN-beta on elements
      in the innate and adaptive immune response were analysed in a longitudinal study.
      We demonstrate significant decreases in anti-Envelope antibody reactivity for the
      two closely related Gammaretroviral human endogenous retroviruses (HERVs), HERV-H
      and HERV-W, as a consequence of IFN-beta therapy, closely linked to efficacy of
      therapy/low disease activity. We also show strong indications of a protective
      effect of high levels of two components in the innate pathogen-associated
      molecular pattern recognition: mannan-binding lectin (MBL), and MBL-associated
      serine protease 3 (MASP-3). Serum levels of typical Th1- and Th2-related, MS
      relevant cytokines were also monitored. Overall both Th1- and Th2-associated
      cytokines were modestly, albeit significantly up-regulated, notably IL-2 and TNF
      alpha (MS patients with inactive disease), as well as IL-4 and, to some extent IL
      10 (no increase in IL-10 for MS patients with active disease (non-responders)).
      We found no overall changes in Th1/Th2 ratios. Our results support that HERV
      H/HERV-W and the antiviral immune response may play a role in MS development, and
      that these HERVs have potential as biomarkers for disease activity.

PMID- 19766329
TI  - Factors of high impacts on the life of caregivers of disabled elderly.
AB  - Elderly caregivers suffer physical and psychological consequences of the act of
      caring. The objective of this study was to characterize primary caregivers of
      elderly people in the community and identify the higher impacts of this activity
      on their life. We interviewed 127 caregivers about sociodemographic
      characteristics, presence of anxiety/depression (self-reporting
      questionnaire=SRQ), burden of care (caregiver burden scale=CBS); while their
      dependents were evaluated using sociodemographic questionnaires, health history,
      activities of daily living (ADL) scale and geriatric depression scale (GDS-15).
      The caregivers' mean age was 55.1+/-13.3 years; among them most were women and
      daughters with up to 4 years of education. The mean time as responsible for the
      elderly was 86.5+/-96.3 months; 56% divided the caring responsibility and 28.2%
      had another occupation; 32.3% presented psychoemotional illness. There was a
      positive correlation between the CBS and the caregiver factors: psychoemotional
      disorders, time as responsible for the elderly and education level; as well as
      between the CBS and the elderly: number of activities with dependence, presence
      of depression and incontinences. The correlation between the elderly's personal
      income and number of visits received was negative. The identification of high
      impacts on the caregivers' life would facilitate the professional approach.

PMID- 19766330
TI  - Chromogranin A (CgA) serum level as a marker of progression in hepatocellular
      carcinoma (HCC) of elderly patients.
AB  - The observation of neuroendocrine (NE) activity during clinical course of
      hepatocellular carcinoma (HCC), suggested the use of NE serum markers to detect
      it. Thus we have evaluated the usefulness of serum measurements of CgA in
      monitoring disease activity of HCC. We investigated the role of serum
      concentrations of CgA, alpha-fetoprotein (AFP) and des-gamma-carboxyl-prothrombin
      (DCP) in 55 patients with HCC, 27 patients with cirrhosis, 22 patients with
      chronic hepatitis and a control group of 20 volunteers and the relationship
      between the pre-treatment serum CgA and clinical stages of the disease. CgA was
      significantly higher in the patients affected by HCC as compared with those
      affected by either hepatitis or cirrhosis (p<0.001). We also observed significant
      differences, comparing CgA serum levels in the tumor classes T1-T4: T1 vs. T2
      (p<0.001), T1 vs. T3 (p<0.001), T1 vs. T4 (p<0.001), T2 vs. T3 (p<0.001), T2 vs.
      T4 (p<0.001) and T3 vs. T4 (p<0.001). CgA levels were significantly higher in
      poorly differentiated HCC vs. well differentiated (p<0.05) and medium
      differentiated ones (p<0.001). Also the comparison between Child-Pugh degree A
      and C showed a significant difference in CgA levels (p<0.001). Thereby, patients
      with higher CgA level had poor survival and showed poor prognosis, compared to
      those with lower CgA level, i.e., the CgA is useful in monitoring progression of
      disease and may assist as a prognostic indicator.

PMID- 19766331
TI  - Exercise intolerance in patients with congenitally corrected transposition of the
      great arteries relates to right ventricular filling pressures.
AB  - BACKGROUND: Patients with congenitally corrected transposition of the great
      arteries (ccTGA) have significantly reduced exercise tolerance. Progressive right
      ventricular (RV) dysfunction with tricuspid regurgitation (TR) and other
      haemodynamic lesions are common among them. We hypothesised that interaction of
      these factors may result in increased systemic RV filling pressure, which in turn
      impact on exercise capacity. METHODS: Patients with ccTGA in functional class I
      or II, able to perform treadmill exercise and without resting cyanosis were
      enrolled. All patients underwent cardiopulmonary exercise testing and
      transthoracic echocardiographic examination. RV filling pressure was estimated
      using tissue Doppler imaging (TDI) techniques by measuring early annular
      diastolic velocity (Ea) and the ratio of the transtricuspid inflow to the early
      annular diastolic velocity (E/Ea). RESULTS: A total of 27 patients (mean age 41
      years, 48% female) were assessed, the majority (63%) asymptomatic. Many patients
      had coexistent haemodynamic lesions including shunts, pulmonary stenosis, TR and
      systemic ventricular dysfunction. Average percentage predicted peak oxygen
      consumption, VE/VCO(2) slope and heart rate reserve were abnormal in this
      population. Patients with moderately/severely impaired exercise capacity (<= 60%
      predicted peak VO(2)) had significantly higher E/Ea ratios compared to those with
      normal/mildly impaired exercise capacity (septal E/Ea = 17.1 +/- 9.7 vs 8.8 +/-
      1.6 and lateral E/Ea = 11.5 +/- 5.8 vs 6.6 +/- 1.3, p = 0.007 and 0.01
      respectively). CONCLUSION: Reduced exercise capacity is common in adults with
      ccTGA even among asymptomatic patients and relates to increased RV filling
      pressures assessed by TDI. This index could potentially be used to optimize
      therapy or prognosticate adverse events in ccTGA patients.

PMID- 19766332
TI  - A high carbohydrate meal yields a lower ischemic threshold than a high fat meal
      in patients with stable coronary disease.
AB  - OBJECTIVE: To assess the ischemic threshold and stress-induced left ventricular
      dysfunction after high fat (HFM) and high carbohydrate (HCM) meals in patients
      with stable coronary disease. METHODS: Twelve patients (68 +/- 7 years) underwent
      stress (treadmill exercise testing) echocardiography after fasting (8h), after
      HFM and HCM (2h). Time to 1mm ST-segment depression (time to 1mm) and stress wall
      motion score index (WMSI) were evaluated. Before eating and just before exercise
      testing glucose, insulin, triglycerides, total cholesterol and FFA levels were
      measured. RESULTS: Results are expressed as medians (Q1-Q3). HFM did not affect
      exercise variables compared to fasting, whereas HCM reduced the ischemic
      threshold [time to 1mm from 376 (343-493) to 297 (180-420) s, p = 0.003].
      Compared to fasting [1.47 (1.31-1.66)], stress WMSI was higher after HCM [1.56
      (1.44-1.69)] (p = 0.04) but not after HFM [1.56 (1.30-1.63)]. Glycemia and
      insulinemia were significantly higher after HCM, compared to fasting and HFM.
      CONCLUSIONS: In patients with coronary disease, exercise testing after a high
      carbohydrate meal results in a lower ischemic threshold and greater ischemia
      magnitude. Conversely, compared to fasting, a high fat meal does not induce
      additional detrimental effects. Hyperglycemia and hyperinsulinemia were the only
      metabolic determinants identified as potential metabolic mechanisms of this
      phenomenon.

PMID- 19766333
TI  - Dog obesity: owner attitudes and behaviour.
AB  - Animal (dog) factors that contribute to obesity are classified into three broad
      categories: genetic pre-disposition, reproductive management and dietary/exercise
      (human) management. This paper examined the latter-dietary/exercise (human)
      management. A quantitative analysis of questionnaire responses from dog owners
      and veterinarians was used to determine the routine care and obesity management
      strategies for dogs. A total of 550 questionnaires were distributed to dog owners
      in Victoria, Australia. Owners were asked to score the body condition of their
      animal by comparison with photographic images of animals with condition score
      ranging from 2 to 5. The management routines of 219 dog owners were received,
      including data on 302 dogs. There were 168 households with normal weight animals
      (BCS 2 and 3) and 51 with obese animals (BCS 4 and 5). The mean number of people
      per household (normally involved with caring for the animal(s)) with normal
      weight dogs was significantly lower than that of households with dogs categorised
      as overweight or obese (Kruskal-Wallis, Chi; chi(2)=6.28; 2.2 (s=0.79) vs. 2.5
      (s=1.66); d.f.=2, P<0.05). Dog owners identified a preference for main meal
      feeding of 'twice a day' (60%), followed by 'once daily' (33%), 'greater than or
      equal to three times daily' (2%), and 'always feed available' (5%). There was a
      significant difference (Chi; chi(2)=6.30; d.f.=1; P<0.05) in the frequency of
      main meal feeding between households. Normal weight animals had food divided into
      two portions, whereas obese animals or animals from mixed households were more
      often fed their meal in either one or three-plus portions. Almost all owners fed
      treats (99%) in the daily feed. Households with normal weight dogs gave treats
      significantly less frequently than households with obese or mixed weight dogs
      (Chi; chi(2)=31.81; d.f.=6; P<0.001). The frequency of exercise differed between
      households (Chi; chi(2)=9.9; d.f.=1; P<0.01), with normal weight dogs being
      exercised daily compared to weekly for overweight or mixed weight dogs. Owners
      who indicated that their dog was confined to a yard as its exercise regime rather
      than walked were also significantly more likely to be an obese or mixed weight
      household (Chi; chi(2)=18.4; d.f.=1; P<0.001). In conclusion, there is clear
      evidence that obesity in dogs is affected by the interrelationships between food
      management, exercise and social factors.

PMID- 19766334
TI  - Meta-analytical equivalence studies on diagnostic tests for bovine brucellosis
      allowing assessment of a test against a group of comparative tests.
AB  - In the assessment of diagnostic tests the task may arise to show that a candidate
      test is non-inferior compared to a comparative (standard) test with regard to the
      diagnostic sensitivity or specificity. This setting is known as "one-sided
      equivalence" and has been applied to a single comparison between two diagnostic
      tests (Chen et al., 2003). Recently, the approach has been extended into a meta
      analytical framework (EFSA, 2006), allowing for the difference between the
      sensitivity (or specificity) of two diagnostic tests to be estimated using
      information gathered through systematic literature review. Using this approach,
      confounding factors are adjusted by matching of parameter estimates on study
      population and preferred levels of the confounding factors. However, the power of
      this approach was found to be limited and therefore Markov chain Monte Carlo
      logistic regression (MCMCLR) models that allow adjustment for confounding
      variables have been developed (EFSA, 2006). We report here a refinement of the
      statistical inference based on the latter approach. The objective was to generate
      a posterior distribution of the meta-analytical difference statistic for the
      candidate test and a set of comparative tests. The algorithm for this purpose
      uses Monte Carlo sampling from the posterior distributions of sensitivity (or
      specificity) and, for each iteration, (i) identifies the least performant
      comparative test, (ii) establishes the difference statistics for this test and
      the candidate test and (iii) compares the difference statistic with a critical
      threshold value. The proportion of iterations in which the critical threshold was
      exceeded is then interpreted as the P-value for the one-sided equivalence test
      for the candidate versus the set of comparative tests. We illustrate and discuss
      the method using a case study on tests for bovine brucellosis.

PMID- 19766335
TI  - Therapeutic application of peptides and proteins: parenteral forever?
AB  - Varied therapeutic peptides and proteins represent a rapidly growing part of
      marketed drugs and have an undisputed place alongside other established
      therapies. Nevertheless, such biodrugs have several drawbacks that hinder their
      therapeutic application. These are undesirable physicochemical properties, such
      as variable solubility, low bioavailability and limited stability. These issues
      can be overcome by addition of stabilizing agents and directed injectable
      administration, which can however result in low patient compliance. Hence, there
      is a drive in the biotechnology industry to produce needle-free and more user
      friendly drugs, and this has led to the growth of nano-enabled drug delivery
      systems in the last decade. As discussed here, nanobiotechnology is becoming a
      commercially feasible and promising opportunity for oral, pulmonary and
      transdermal administration routes.

PMID- 19766336
TI  - Carbon-11 acetate PET/CT based dose escalated IMRT in prostate cancer.
AB  - PURPOSE: To demonstrate the theoretical feasibility of [(11)C]acetate PET/CT in
      delineating the malignant intraprostatic lesions (IPL's) in prostate cancer and
      to use the data in external beam radiotherapy to boost the biologically defined
      target volume (BTV). METHODS AND MATERIALS: Twelve men with intracapsular
      prostate carcinoma were imaged with [(11)C]acetate PET/CT and the data were used
      to delineate the BTV. Six dynamic IMRT plans were generated to each patient: a
      standard IMRT (sIMRT) plan with a 77.9 Gy dose to PTV (prostate gland with a 6-mm
      margin) and a simultaneous integrated boost IMRT (SIB(IMRT)) plan to deliver 77.9
      Gy, 81 Gy, 84 Gy, 87 Gy and 90 Gy to the BTV and 72 Gy to the rest of PTV. To
      study the theoretical dose escalation based on the delineation of BTV, tumor
      control probabilities (TCPs) and normal tissue complication probabilities (NTCPs)
      of bladder and rectum were calculated and compared between the treatment plans.
      RESULTS: [(11)C]Acetate was used to delineate the IPL's of all 12 patients. With
      every patient the TCP was increased with SIB(IMRT) without increasing the NTCP of
      the bladder or rectum. The probability of uncomplicated control (PUC) was
      increased on average by 28% with the SIB(IMRT) treatment plans. The highest PUC
      was achieved with an average dose of 82.1 Gy to the BTV. CONCLUSIONS: Our study
      indicates that [(11)C]acetate can be used to define the IPL's and in combination
      with SIB(IMRT) the defined areas can theoretically be treated to ultra high doses
      without increasing the treatment toxicity. These results motivate the formal
      validation of [(11)C]acetate PET for biological dose planning in prostate cancer.

PMID- 19766337
TI  - Late toxicity after postprostatectomy salvage radiation therapy.
AB  - PURPOSE: To evaluate late toxicity in patients who received salvage external beam
      radiotherapy (EBRT) for a detectable prostate-specific antigen (PSA) level after
      radical prostatectomy (RP). METHODS: A cohort of 308 consecutive patients
      underwent salvage EBRT from July 1987 through June 2003 for a detectable PSA
      level after RP. All were treated with high-energy photons (6-20 MV) to a median
      dose of 64.8 Gy (range: 54.0-72.4 Gy) in 1.8- to 2.0-Gy fractions. RESULTS:
      Median follow-up from the completion of EBRT was 60 months (range: 1 day-174
      months). Late toxicity occurring more than 90 days after EBRT completion was
      identified in 41 patients (13%). Twelve patients (3.9%) had grade 2 urethral
      strictures and were treated with urethral dilation, 3 patients had grade 3
      cystitis, and 1 had a grade 4 rectal complication. These numbers correspond to an
      estimated 0.7% (95% confidence interval, 0.0-1.6%) of patients experiencing a
      grade 3 or 4 complication by 5 years after the start of EBRT. CONCLUSIONS:
      Salvage EBRT for a detectable PSA level after RP is the only curative treatment
      in this setting. This treatment can be administered in a manner that results in a
      low likelihood of late complications.

PMID- 19766338
TI  - IMRT significantly reduces acute toxicity of whole-pelvis irradiation in patients
      treated with post-operative adjuvant or salvage radiotherapy after radical
      prostatectomy.
AB  - PURPOSE: To investigate the role of IMRT in reducing the risk of acute genito
      urinary (GU), upper gastrointestinal (uGI) and lower gastrointestinal (lGI)
      toxicity following whole-pelvis irradiation (WPRT) after radical prostatectomy.
      PATIENTS AND METHODS: 172 consecutive patients with prostate cancer were post
      operatively irradiated to the prostatic bed (PB) and pelvic lymph-nodal area with
      adjuvant (n=100) or salvage (n=72) intent. Eighty-one patients underwent three
      dimensional conformal (3DCRT) WPRT, while the remaining 91 underwent IMRT (54/91
      with helical tomotherapy (HTT); 37/91 with Linac intensity-modulated RT
      (LinacIMRT)). RESULTS: Patients treated with IMRT experienced a decreased risk of
      acute toxicity. The crude incidence of grade > or =2 toxicity was GU 12.3% vs.
      6.6% (p=0.19); lGI 8.6% vs. 3.2% (p=0.14); uGI 22.2% vs. 6.6% (p=0.004), for
      3DCRT and IMRT, respectively. With respect to uGI and lGI, the acute toxicity
      profile of the HTT patients was even better when compared to that of 3DCRT
      patients (crude incidence:1.8% and 0.0%, respectively). Treatment interruptions
      due to uGI toxicity were 11/81 in the 3DCRT group vs. 2/91 in the IMRT group
      (p=0.006). CONCLUSIONS: The risk of acute toxicity following post-operative WPRT
      delivered by means of IMRT was reduced compared to that of 3DCRT. The most
      significant reduction concerned uGI, mainly owing to better bowel sparing with
      IMRT.

PMID- 19766339
TI  - Modeling set-up error by daily MVCT for prostate adjuvant treatment delivered in
      20 fractions: Implications for the assessment of the optimal correction
      strategies.
AB  - PURPOSE: To optimise image-guided radiotherapy (IGRT) approaches in set-up error
      correction for hypofractionated adjuvant treatment of prostate cancer using
      helical tomotherapy (HT). METHODS AND MATERIALS: HT unit provides megavoltage -
      CT (MVCT) imaging capability for daily patient set-up. The intrinsic uncertainty
      of the available image registration techniques was first investigated on a pelvic
      phantom. To optimise different set-up correction strategies, MVCT data of 37
      patients treated with 58 Gy delivered in 20 fractions were analyzed. 620 MVCT
      images were globally available for the analysis. Daily on-line set-up correction
      without any action level was applied for 27/37 patients. The residual and the
      effective set-up error were assessed. For 10/37 patients an off-line correction
      strategy with an action level was applied. RESULTS: Phantom measurements showed
      an intrinsic uncertainty in MVCT imaging and registration around 0.6 mm (+/-0.5
      mm) for each of the three main axes. The minimum value of the residual systematic
      error was found at 7th-10th session, with values between 0.7 and 1.1 mm (1 SD); a
      systematic residual error <2 mm for all directions was in any case found at 3rd
      4th session. This result was also confirmed by the effective systematic set-up
      error analysis, with a minimum value within 1.5mm nearly at the 4th or 5th
      fraction. CONCLUSIONS: Although the minimum systematic residual error is reached
      at 7th-10th treatment session, the effective systematic set-up error analysis
      confirmed that an off-line correction at the 4th fraction without any action
      level may be a robust compromise with a large sparing of time and resources
      compared to on-line correction.

PMID- 19766340
TI  - Incidence of isolated regional recurrence after definitive (chemo-) radiotherapy
      for head and neck squamous cell carcinoma.
AB  - OBJECTIVE: To evaluate the incidence and localization of regional recurrences
      after definitive (chemo-) radiotherapy for head and neck squamous cell carcinoma
      (HNSCC). METHODS: From May 1987 to March 2008, 368 patients with advanced HNSCC
      were irradiated to 66-80.5 Gray in 6-7 weeks, with (37%) or without (63%)
      concomitant chemotherapy (Cisplatinum 100mg/m(2)) every 3 weeks. No planned neck
      dissections were performed. Data on clinical outcome were retrospectively
      reviewed, location of the original nodal disease and the regional recurrence was
      indicated on imaging and correlated with radiation dose. RESULTS: Mean follow-up
      was 34 months (range: 50 days-216 months). Three-year overall survival and
      disease-specific survival were 55% and 62%, respectively. Loco-regional, local
      and regional controls were 58%, 65%, and 80%, respectively. Forty-one patients
      (11.1%) relapsed in the neck, but only 11 patients (2.99%) developed a true
      isolated regional recurrence, 6 of whom could be successfully salvaged by
      surgery. Only 2 patients (0.54%) developed an isolated recurrence in the
      electively treated nodal levels. CONCLUSION: Isolated nodal recurrences are
      uncommon and recurrences in the electively treated neck are extremely uncommon.

PMID- 19766341
TI  - Racial differences in the discussion and treatment of depressive symptoms
      accompanying type 2 diabetes.
AB  - OBJECTIVE: To compare rates of discussion of and treatment for depression among
      African Americans and Whites with diabetes. METHODS: Measures of diabetes status,
      depressive symptoms, and history of discussing and being treated for depression
      were collected from 56 adults with elevated depressive symptoms accompanying
      diabetes who were drawn from a larger study of type 2 diabetes. RESULTS: Analyses
      adjusted for confounders and multiple tests indicated that relative to Whites,
      African Americans were 6-12 times less likely to have ever: discussed depression
      with anyone (p=.007), discussed depression with their primary care physician
      (p=.008), been prescribed an antidepressant (p=.002), and they were 25 times less
      likely to have seen a psychiatrist (p=.003). There were no significant
      differences in discussing depression with clergypersons, or family
      members/friends. CONCLUSIONS: Compared to their White counterparts, African
      Americans with depressive symptoms accompanying diabetes are unlikely to discuss
      depression with healthcare professionals, be prescribed antidepressant
      medication, or be seen by a psychiatrist. Minority diabetes patients' medical and
      psychiatric outcomes may improve if healthcare providers more actively initiate
      these discussions, provide culturally tailored education about the nature of
      depression and its management, incorporate patient preferences into treatment
      plans, and establish relationships with persons more likely to learn about
      African American patient symptoms.

PMID- 19766342
TI  - The relation of ADMA and apelin to endothelial dysfunction and angiogenesis in
      patients with type 2 diabetes mellitus.

PMID- 19766343
TI  - Microvascular diabetic complications are more prevalent in India compared to
      Mauritius and the UK due to poorer diabetic control.
AB  - Type 2 diabetes mellitus (T2DM) is a growing worldwide problem with WHO estimates
      suggesting that 300 million people will be affected by 2025. T2DM could result in
      both microvascular and macrovascular complications but the presentation of these
      complications could vary globally and be influenced by diabetic control. We
      investigated the prevalence of these complications by surveying 787 patients of
      south-Asian origin in diabetic clinics in the UK (n=351), Mauritius (n=173) and
      India (n=263). We found the prevalence of microvascular complications such as
      retinopathy (India 16.3%; Mauritius 2.3%; UK 2.6%), nephropathy (India 20.5%;
      Mauritius 10.5%; UK 2.3%) and neuropathy (India 8.4%; Mauritius 1.2%; UK 5.1%)
      complications to be significantly higher in India compared to Mauritius and the
      UK (p<0.05). Interestingly, macrovascular complications such as cardiovascular
      disease were significantly more prevalent in Mauritius and the UK compared to
      India (p<0.05). The use of diabetic medication such as Metformin, Sulphonylureas
      and Insulin was significantly higher in the UK and Mauritius compared to India
      (p<0.05). The mean HbA1c was significantly higher in India compared to the UK
      (India 8.68%; UK 8.30%). Our results suggest that microvascular complications are
      higher in India due to poorer diabetic control. Our findings could be explained
      by late-onset presentation of diabetic patients in India due to the lack of
      primary care initiatives to screen and monitor treatment of T2DM. Furthermore,
      the poor diabetic control in India could reflect a dearth of clinical, evidence
      based-knowledge regarding diabetic medication amongst Indian physicians. In view
      of the global increase in T2DM, this is a major concern for Indian healthcare.

PMID- 19766344
TI  - The incidence of type 2 diabetes mellitus in the Philippines: a 9-year cohort
      study.
AB  - AIMS: Currently, there are no available data on the incidence of type 2 diabetes
      mellitus (T2DM) in the Philippines. A cohort derived from a national study
      population (FNRI-NNS, 1998) was revisited after 9 years to yield valuable data on
      glucose homeostasis among Filipinos. METHODS: Six out of 13 national regions were
      included in the cohort. There were 1749 out of 2122 respondents (82.4%). 1386
      (95.9%) consented to a fasting blood glucose (FBG) test, and 1275 (88.2%)
      completed the 2h post-glucose (2HPG) load determination using whole blood
      capillary samples. RESULTS: We observed a significant increase of mean FBGs
      (91.5mg/dL to 103.3mg/dL) from 1998 to 2007. The 9-year incidence of T2DM was
      16.3%. The prevalence of T2DM was 28.0%. The prevalence of pre-diabetes, i.e.,
      combined impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) was
      31.3%; IFG was 17.5% and IGT was 23.9%. CONCLUSIONS: The study shows the alarming
      growth of diabetes, IFG, and IGT in our country that warrants early aggressive
      intervention for prevention and management. We encourage the use of 2h post
      glucose load aside from FBG in screening for true diabetics, IFGs, and IGTs.

PMID- 19766345
TI  - Intrinsic value: a reply to Justus et al.

PMID- 19766346
TI  - Analysis of CXCL9 and CXCR3 expression in a case of intravascular large B-cell
      lymphoma.
AB  - Intravascular large B-cell lymphoma is a rare disease with multiorgan involvement
      that also affects the skin. Skin manifestations include purpuric to red macules,
      plaques, or nodules with occasional edema and tenderness. We report a 68-year-old
      woman with bilateral leg edema and occasional high fever. A biopsy specimen from
      a subcutaneous nodule showed that the blood vessels in the dermis and
      subcutaneous tissue were filled with irregularly shaped chromatin-rich large
      atypical lymphocytes positive for CD20 and bcl-2, consistent with the diagnosis
      of intravascular large B-cell lymphoma. In addition, immunohistochemical analysis
      showed expression of CXCR3 in the atypical lymphocytes; its ligand, CXCL9, was
      detected in blood vessels. Although limited to a single case, our study could
      provide a possible new clue to the pathogenesis of intravascular large B-cell
      lymphoma by virtue of the characteristic expression of CXCL9-CXCR3.

PMID- 19766347
TI  - Amelanotic lentigo maligna: a report of three cases and review of the literature.
AB  - BACKGROUND: Amelanotic lentigo maligna is not clinically suspected and is often
      mistaken for a basal cell carcinoma, squamous cell carcinoma, or dermatitis.
      OBJECTIVE: Our objective was to review previously reported cases of amelanotic
      lentigo maligna and compare them with our 3 cases. METHODS: The clinical
      presentation and histologic findings of 3 new cases are described and compared
      with those in the literature. RESULTS: The index of suspicion for amelanotic
      lentigo maligna is extremely low. No reported cases have been diagnosed
      clinically. None of our 3 cases was suspected. LIMITATIONS: Only three cases were
      reviewed. CONCLUSION: A high degree of clinical and histologic suspicion is
      required to make the diagnosis of this clinically nondescript neoplasm.

PMID- 19766348
TI  - Large congenital melanocytic nevi and neurocutaneous melanocytosis: one pediatric
      center's experience.
AB  - BACKGROUND: Large congenital melanocytic nevi (LCMN) predispose to neurocutaneous
      melanocytosis (NCM), which is associated with significant morbidity and
      mortality. OBJECTIVE: To identify risk factors for NCM in patients with LCMN and
      suggest guidelines for their management. METHODS: Medical records of patients
      with LCMN were reviewed at Sainte-Justine Hospital between 1980 and 2006.
      Presence of multiple satellite nevi and posterior midline location were evaluated
      as risk factors for NCM using chi-square test. Magnetic resonance imaging scans
      were reviewed by a neuroradiologist. RESULTS: Twenty-six of 52 patients underwent
      radiologic investigation. Six of 26 (23%) had NCM. Patients with this condition
      are more likely to have multiple satellite nevi (100% vs 50%, P = .03) and have a
      trend to posterior midline location of their LCMN (100% vs 60%, P = .08).
      Patients with NCM are more likely to have both multiple satellite nevi and
      posterior midline location (100% vs 25%, P = .002). Radiologic findings are also
      presented. LIMITATIONS: This was a retrospective case series with imprecise chart
      data in 38% of cases. CONCLUSION: The presence of multiple satellite nevi alone
      or with associated posterior midline location of LCMN is associated with a higher
      risk of NCM. We recommend magnetic resonance imaging testing before 4 months of
      age in patients with these features.

PMID- 19766349
TI  - Mutations in lipase H cause autosomal recessive hypotrichosis simplex with woolly
      hair.
AB  - BACKGROUND: Mutations in lipase H (LIPH) are a rare cause of autosomal recessive
      hypotrichosis (HT) simplex. OBJECTIVE: In this study, we investigated the
      clinical and molecular basis of HT simplex with woolly hair in 3 nonrelated
      families. METHODS: Three families of Jewish, Arab Muslim, and Italian origin that
      presented with HT with woolly hair were studied. The phenotype was confirmed by
      clinical, microscopic, and histologic examination. Polymorphic microsatellite
      genotyping and direct automated DNA sequencing of the LIPH gene were used to
      identify the mutations in our probands. RESULTS: All patients had woolly hair
      since birth. At presentation, scalp hair density was reduced or normal.
      Sequencing of the LIPH gene revealed two homozygous mutations: a large recurrent
      90-base pair duplication mutation in exon 2 in the Jewish and Arab families, and
      a novel deletion/insertion mutation in exon 4 in the Italian family. LIMITATIONS:
      Only 3 families were studied. CONCLUSION: Mutations in LIPH result in variable
      degrees of HT. Woolly hair is an essential component of the clinical spectrum. A
      hot spot in the LIPH gene may be c.280_369dup in exon 2.

PMID- 19766350
TI  - Randomized, double-blind, placebo-controlled evaluation of the efficacy of oral
      psoralen plus ultraviolet A for the treatment of plaque-type psoriasis using the
      Psoriasis Area Severity Index score (improvement of 75% or greater) at 12 weeks.
AB  - BACKGROUND: Psoralen plus ultraviolet A (PUVA) for the treatment of psoriasis has
      never been evaluated using the Psoriasis Area Severity Index (PASI) in a
      randomized, double-blind, placebo-controlled trial. The lack of such data limits
      our capacity to estimate PUVA's efficacy relative to other treatment options that
      are available today. OBJECTIVES: The purpose of this study was to evaluate the
      efficacy of PUVA therapy for patients with plaque-type psoriasis. METHODS: This
      study involved 40 patients with psoriasis; 30 received PUVA and 10 received UVA
      with placebo. PASI scores were assessed at baseline and every 4 weeks thereafter
      for 12 weeks. RESULTS: By nonresponder imputation, 60% (18 of 30) in the PUVA
      group achieved 75% or more improvement in PASI score after 12 weeks of treatment
      compared with 0% (0 of 10) in the UVA plus placebo group (P < .0001). Using
      intent to treat with last observation carried forward analysis, 63% (19 of 30) in
      the PUVA group achieved 75% or more improvement in PASI score compared with 0% (0
      of 10) in the UVA plus placebo group (P < .0001). By per protocol analysis, 86%
      (18 of 21) in the PUVA group as compared with 0% (0 of 7) in the UVA plus placebo
      group reached 75% or more improvement in PASI score after 12 weeks (P < .0001).
      LIMITATIONS: The study was relatively small with only 40 patients enrolled and 28
      patients who completed the protocol. Further studies that involve head-to-head
      comparison of PUVA with other treatment modalities are needed. Nonresponder
      imputation, last observation carried forward with intent to treat, and per
      protocol analyses each have separate advantages and limitations when determining
      clinical significance. CONCLUSIONS: This study supports the observation that PUVA
      is a highly efficacious treatment for chronic plaque psoriasis.

PMID- 19766351
TI  - Eruptive postoperative squamous cell carcinomas exhibiting a pathergy-like
      reaction around surgical wound sites.
AB  - BACKGROUND: The isomorphic response of Koebner and the pathergy skin reaction
      have not classically been associated with neoplastic processes such as cutaneous
      squamous cell carcinoma (SCC). OBJECTIVE: We report 5 patients who developed
      postoperative eruptive SCCs within and around the healed or healing sites of
      excised nonmelanoma skin cancers. The original cancers were all excised with
      histologically tumor-free margins and the subsequent eruptive SCCs were sometimes
      multiple. METHODS: We performed follow-up examinations of patient's wounds after
      the treatment of skin cancer with Mohs micrographic surgery. Keratotic nodules
      that developed acutely in the margins of healing wound sites of these patients
      were examined histologically by a single dermatopathologist. RESULTS: The tumors
      presented as rapidly growing keratotic nodules within the sites of previously
      excised cancers. The mean time of clinical appearance was approximately 6 weeks
      and histologic examination of the nodules demonstrated well-differentiated SCC.
      LIMITATIONS: This study is limited by its relatively small number of cases.
      CONCLUSION: Acutely eruptive SCC is a rare but significant postoperative
      complication of skin cancer surgery. Furthermore, this case series suggests that
      some individuals appear to be predisposed to this recurrent, pathergy-like
      reaction involving SCC.

PMID- 19766352
TI  - Acute detection of ST-elevation myocardial infarction missed on standard 12-Lead
      ECG with a novel 80-lead real-time digital body surface map: primary results from
      the multicenter OCCULT MI trial.
AB  - STUDY OBJECTIVE: Although 80-lead ECG body surface mapping is more sensitive for
      ST-elevation myocardial infarction (STEMI) than the 12-lead ECG, its clinical
      utility in chest pain in the emergency department (ED) has not been studied. We
      sought to determine the prevalence, clinical care patterns, and clinical outcomes
      of patients with STEMI identified on 80-lead but not on 12-lead (80-lead-only
      STEMI). METHODS: The Optimal Cardiovascular Diagnostic Evaluation Enabling Faster
      Treatment of Myocardial Infarction trial was a multicenter prospective
      observational study of moderate- to high-risk chest pain patients presenting to
      the ED. Patients received simultaneous 12-lead and 80-lead ECGs as part of their
      initial evaluation and were treated according to the standard of care, with
      clinicians blinded to the 80-lead results. The primary outcome of the trial was
      door-to-sheath time in patients with 80-lead-only STEMI versus patients with
      STEMI identified by 12-lead alone (12-lead STEMI). Secondary outcomes included
      angiographic and clinical outcomes at 30 days. RESULTS: One thousand eight
      hundred thirty patients were evaluated, 91 had a discharge diagnosis of 12-lead
      STEMI, and 25 patients met criteria for 80-lead-only STEMI. Eighty-four of the 91
      12-lead STEMI patients underwent cardiac catheterization, with a median door-to
      sheath time of 54 minutes, versus 14 of the 25 80-lead-only STEMI patients, with
      a door-to-sheath time of 1,002 minutes (estimated treatment difference in
      median=881; 95% confidence interval 181 to 1,079 minutes). Clinical outcomes and
      revascularization rates, however, were similar between 80-lead-only STEMI and 12
      lead STEMI patients. CONCLUSION: The 80-lead ECG provides an incremental 27.5%
      increase in STEMI detection versus the 12-lead. Patients with 80-lead-only STEMI
      have adverse outcomes similar to those of 12-lead STEMI patients but are treated
      with delayed or conservative invasive strategies.

PMID- 19766353
TI  - 12-lead ECG findings of pulmonary hypertension occur more frequently in emergency
      department patients with pulmonary embolism than in patients without pulmonary
      embolism.
AB  - STUDY OBJECTIVE: Acute pulmonary embolism can produce abnormalities on ECG that
      reflect severity of pulmonary hypertension. Early recognition of these findings
      may alter the estimated pretest probability of pulmonary embolism and prompt more
      aggressive treatment before hemodynamic instability ensues, but it is first
      important to test whether these findings are specific to patients with pulmonary
      embolism. We hypothesize that ECG findings consistent with pulmonary hypertension
      would be observed more frequently in patients with pulmonary embolism. METHODS:
      Secondary analysis of a prospective, observational cohort of emergency department
      patients who were tested for pulmonary embolism. ECGs were ordered at clinician's
      discretion and interpreted at presentation. RESULTS: Six thousand forty-nine
      patients had an ECG, 354 (5.9%) of whom were diagnosed with pulmonary embolism.
      The frequency, positive likelihood ratio (LR+) and 95% confidence interval (CI)
      of each predictor were as follows: S1Q3T3 8.5% with pulmonary embolism versus
      3.3% without pulmonary embolism (LR+ 3.7; 95% CI 2.5 to 5.4); nonsinus rhythm,
      23.5% versus 16.6% (LR+ 1.4; 95% CI 1.2 to 1.7); inverted T waves in V1 to V2,
      14.4% versus 8.1% (LR+ 1.8; 95% CI 1.3 to 2.3); inversion in V1 to V3, 10.5%
      versus 4.0% (LR+ 2.6; 95% CI 1.9 to 3.6); inversion in V1 to V4, 7.3% versus 2.0%
      (LR+ 3.7; 95% CI 2.4 to 5.5); incomplete right bundle branch block, 4.8% versus
      2.8% (LR+ 1.7; 95% CI 1.0 to 2.7); tachycardia (pulse rate >100 beats/min), 28.8%
      versus 15.7% (LR+ 1.8; 95% CI 1.5 to 2.2). Likelihood ratios and specificities
      were similar when patients with previous cardiopulmonary disease were excluded
      from analysis. CONCLUSION: Findings of acute pulmonary hypertension were
      infrequent overall but were observed more frequently in patients with the final
      diagnosis of pulmonary embolism compared with patients who do not have pulmonary
      embolism.

PMID- 19766354
TI  - Levosimendan as a rescue drug in experimental propranolol-induced myocardial
      depression: a randomized study.
AB  - STUDY OBJECTIVE: Severe beta-blocker intoxication remains a clinical challenge
      despite a variety of treatment options. Because of its unique mechanism of
      action, the new calcium sensitizer levosimendan may provide more prominent
      cardiac support compared with current medications used to reverse negative
      inotropy. We hypothesize that levosimendan could reverse propranolol-induced
      severe negative inotropy in a porcine model of beta-blocker intoxication.
      METHODS: Twenty-four pigs were anesthetized and monitored. After severe
      propranolol intoxication was completed, animals were randomized into 3 groups.
      With a double-blind procedure, 9 animals received a 1.25-mg levosimendan bolus,
      followed by saline solution infusion, 9 animals received mean arterial pressure
      targeted dobutamine infusion after saline solution bolus, and 6 animals received
      a saline solution bolus followed by saline solution infusion. Hemodynamic and
      laboratory data were collected during a follow-up period of 120 minutes. RESULTS:
      All 9 pigs in the levosimendan group survived. In contrast, 4 of 6 (67%) and 7 of
      9 (78%) pigs died during the experiment in the placebo and the dobutamine groups,
      respectively. The levosimendan group showed improved change in the maximum
      positive slope of the left ventricular pressure, cardiac output, stroke volume,
      and mean arterial pressure compared with the dobutamine and the placebo groups.
      CONCLUSION: Levosimendan improved hemodynamic function and survival in this
      animal model of severe propranolol intoxication. The potential clinical
      application of levosimendan in propranolol intoxication warrants further
      investigation.

PMID- 19766355
TI  - Predictors of 30-day serious events in older patients with syncope.
AB  - STUDY OBJECTIVE: We identify predictors of 30-day serious events after syncope in
      older adults. METHODS: We reviewed the medical records of older adults (age > or
      =60 years) who presented with syncope or near syncope to one of 3 emergency
      departments (EDs) between 2002 and 2005. Our primary outcome was occurrence of a
      predefined serious event within 30 days after ED evaluation. We used
      multivariable logistic regression to identify predictors of 30-day serious
      events. RESULTS: Of 3,727 potentially eligible patients, 2,871 (77%) met all
      eligibility criteria. We excluded an additional 287 patients who received a
      diagnosis of a serious clinical condition while in the ED. In the final study
      cohort (n=2,584), we identified 173 (7%) patients who experienced a 30-day
      serious event. High-risk predictors included age greater than 90 years, male sex,
      history of an arrhythmia, triage systolic blood pressure greater than 160 mm Hg,
      abnormal ECG result, and abnormal troponin I level. A low-risk predictor was a
      complaint of near syncope rather than syncope. A risk score, generated by summing
      high-risk predictors and subtracting the low-risk predictor, can stratify
      patients into low- (event rate 2.5%; 95% confidence interval [CI] 1.4% to 3.6%),
      intermediate- (event rate 6.3%; 95% CI 5.1% to 7.5%), and high-risk (event rate
      20%; 95% CI 15% to 25%) groups. CONCLUSION: We identified predictors of 30-day
      serious events after syncope in adults aged 60 years and greater. A simple score
      was able to stratify these patients into distinct risk groups and, if externally
      validated, might have the potential to aid ED decisionmaking.

PMID- 19766356
TI  - The 80-lead ECG: more expensive NSTEMI or Occult STEMI.

PMID- 19766357
TI  - [What should be done and not done throughout the process of dementia? Dialogue
      and aid].
AB  - Because dementia is a powerful predictor of dependence, people with this disease
      are those that live longest with disability. Dementia is the chronic disease
      provoking the greatest dependence at 12, 24, and 36 months after diagnosis, ahead
      of other diseases such as stroke, Parkinson's disease and cardiovascular disease.
      Many of us are aware of the devastating consequences of dementia, but few know
      how to recognize the symptoms in the initial phases. To rectify this situation,
      increased public information and training for health professionals is required.
      To improve the care of the distinct phases of dementia, progress must be made in
      three areas: dementia must be considered a public health priority, the erroneous
      belief that nothing can be done for patients with a diagnosis of dementia must be
      combatted and, finally, no less importantly, knowledge of how to recognize
      incipient dementia must be acquired. People with dementia less frequently receive
      palliative care than patients with cancer, despite clearly sharing the need for
      care in the advances stages of the disease and frequent requests by relatives and
      carers. In summary, action can be taken to improve the early diagnosis of
      dementia and the care of the distinct phases of the disease, thus delaying and/or
      minimizing dependency. Finally, comfort measures at the end stage can be
      improved.

PMID- 19766359
TI  - [A 50-year-old HIV-infected woman with a cheek perforation].

PMID- 19766360
TI  - [Active drugs against Mycobacterium tuberculosis].
AB  - Treatment for Mycobacterium tuberculosis must be lengthy because populations of
      this bacillus differ in metabolic activity, and it must include various
      associated drugs, since spontaneous chromosome mutations can give rise to drug
      resistance. The multiresistant phenotype emerges with sequential acquisition of
      mutations in several independent loci. Thus, the main challenges in tuberculosis
      treatment are resistant strains and reductions in treatment duration and dose to
      facilitate adherence on the part of the patient. The drugs should be fast acting,
      active against resistant strains, and able to eradicate slowly metabolizing
      populations. Progress in recent years has led to the development of analogs of
      first-line antituberculosis drugs with longer dosing intervals (rifamycin
      derivatives) or shorter treatment courses (moxifloxacin, gatifloxacin).
      Nonetheless, new drugs that additionally have novel mechanisms of action and no
      cross-resistance to current first-line drugs are needed. This review describes
      the characteristics, activity, resistance mechanisms, and side effects associated
      with antituberculosis drugs.

PMID- 19766361
TI  - Knowledge and attitudes of surgical trainees towards nutritional support: food
      for thought.
AB  - BACKGROUND & AIMS: Up to 40% of patients admitted to UK hospitals are
      malnourished and appropriate nutritional intervention can improve outcomes. We
      investigated the knowledge and attitudes of UK surgical trainees towards
      nutritional support and compared their responses with dieticians. METHODS:
      Trainee surgeons and qualified dieticians were asked to complete a multiple
      choice question test derived from topics relating to nutritional support,
      followed by a questionnaire on their attitudes towards nutrition. Participants
      were unaware that they would be tested. RESULTS: The test was administered to 63
      doctors and 25 dieticians. There were 19 newly qualified doctors (foundation year
      1 [FY(1)]), 21 junior surgeons (speciality-training years 1 and 2 [ST(1-2)]) and
      23 senior surgeons (speciality-training years 3 and above [ST(3+)]). Mean [SE]
      test scores were lower for doctors compared to dieticians (14.0 [0.64] versus
      26.4 [0.22], p<0.001). The respective test scores for FY(1), ST(1-2), ST(3+)
      doctors were 9.8 [0.78], 14.3 [1.10] and 17.3 [0.76]. Only 47% of doctors felt
      they had adequate knowledge of this subject and 65% stated that they regularly
      made decisions on nutritional support. Furthermore, only 25% stated they could
      calculate daily energy and nutritional requirements. CONCLUSION: Despite making
      decisions related to nutritional support regularly, surgical doctors in the UK
      demonstrated less knowledge of the fundamental principles of nutritional support
      than dieticians.

PMID- 19766362
TI  - Expression and importance of inhibitor of DNA binding helix-loop-helix protein in
      salivary adenoid cystic carcinoma.
AB  - Studies have reported that Id-1 (inhibitor of DNA binding, or differentiation 1)
      protein, helix-loop-helix (HLH) transcription factor, has important roles in the
      development of several carcinomas. However, the role of Id-1 protein in salivary
      adenoid cystic carcinoma (ACC) is not clear. The expression of Id-1 protein was
      assessed in formalin-fixed, paraffin-embedded surgical specimens of ACCs by
      immunohistochemical staining. Thirty-nine of the 54 specimens of ACC stained for
      Id-1expression, which was significantly more than was found in pleomorphic
      adenomas (4/12) and normal salivary gland tissues (1/10, p<0.05). There were also
      significant differences between stages I and II (7/14) and III-IV (32/40)
      (p<0.05). Of tumours with metastases, 31/38 stained for Id-1, which was
      significantly higher than among those without metastases (8/16) (p<0.05). Our
      results showed that Id-1 may have important roles in the development of salivary
      ACC. It might also be a useful therapeutic tool to help prevent salivary ACC or
      to inhibit its malignant progression.

PMID- 19766363
TI  - Effect of hip protectors, falling angle and body mass index on pressure
      distribution over the hip during simulated falls.
AB  - BACKGROUND: We examined how a soft shell hip protector affects the magnitude and
      distribution of force to the hip during simulated falls, and how the protective
      effect depends on the fall direction and the amount of soft tissue padding over
      the hip. METHODS: Fourteen young women with either high or low body mass index
      participated in a "pelvis release experiment" that simulated falls resulting in
      either lateral, anterolateral or posterolateral impact to the pelvis with/without
      a soft shell hip protector. Outcome variables were the magnitude and location of
      peak pressure (d, theta) with respect to the greater trochanter, total impact
      force, and percent force applied to four defined hip regions. FINDINGS: The soft
      shell hip protector reduced peak pressure by 70%. The effect was two times
      greater in low than high body mass index individuals. The protector shunted the
      peak pressure distally along the shaft of the femur (d=52 mm (SD 22), theta=-21
      degrees (SD 49) in the unpadded trials versus d=81 mm (SD 23), theta=-10 degrees
      (SD 35) in the padded trials). Peak force averaged 12% greater in posterolateral
      and 17% lower in anterolateral than lateral falls. INTERPRETATION: Our results
      indicate that the hip protector we tested had a much stronger protective benefit
      for low than high body mass index individuals. Next generation protectors might
      be developed for improved shunting of pressure away from the femur, improved
      protection during posterolateral falls, and greater force attenuation for low
      body mass index individuals.

PMID- 19766364
TI  - Young and older adults use different strategies to perform a standing turning
      task.
AB  - BACKGROUND: Falls are the leading cause of death in adults over 65 years of age.
      Falls during turning are likely to result in costly and debilitating hip
      fractures. Two-thirds of adults who fracture a hip will never regain their
      previous level of independence. The purpose of this study, therefore, was to
      examine performance of turning in place in young and older adults. METHODS: Ten
      young (mean age=25 years) and 10 community-dwelling older adults (mean age=75
      years) performed a standing turning task under two conditions: feet constrained
      and feet unconstrained. Dependent measures were rotational range of motion of the
      head-on-trunk, trunk-on-pelvis, pelvis and feet; trunk flexion/extension and knee
      flexion; and center of pressure range and center of mass range in both the
      anterior-posterior and medial-lateral directions. FINDINGS: In both conditions,
      older adults used less head-on-trunk but more trunk-on-pelvis rotation than the
      young adults. In the constrained condition, older adults also used more trunk
      extension and knee flexion than the young adults. In the unconstrained condition,
      more of the older adults moved their feet (60% vs. 30% of young adults). These
      differences in segmental motion resulted in greater center of mass movement for
      the older adults in the constrained but not the unconstrained foot condition.
      INTERPRETATIONS: Older adults show changes in segmental spinal range of motion
      associated with postural instability while turning in place. Foot movements play
      an essential role in compensating for these changes and maintaining postural
      stability.

PMID- 19766365
TI  - Analysis of a Farquhar-von Caemmerer-Berry leaf-level photosynthetic rate model
      for Populus tremuloides in the context of modeling and measurement limitations.
AB  - The balance of mechanistic detail with mathematical simplicity contributes to the
      broad use of the Farquhar, von Caemmerer and Berry (FvCB) photosynthetic rate
      model. Here the FvCB model was coupled with a stomatal conductance model to form
      an [A,g(s)] model, and parameterized for mature Populus tremuloides leaves under
      varying CO(2) and temperature levels. Data were selected to be within typical
      forest light, CO(2) and temperature ranges, reducing artifacts associated with
      data collected at extreme values. The error between model-predicted
      photosynthetic rate (A) and A data was measured in three ways and found to be up
      to three times greater for each of two independent data sets than for a base-line
      evaluation using parameterization data. The evaluation methods used here apply to
      comparisons of model validation results among data sets varying in number and
      distribution of data, as well as to performance comparisons of [A,g(s)] models
      differing in internal-process components.

PMID- 19766366
TI  - Exposure of the marine deposit feeder Hydrobia ulvae to sediment associated LAS.
AB  - Linear Alkylbenzene Sulfonates (LAS) effects (mortality, egestion rate,
      behaviour) on the marine deposit feeder Hydrobia ulvae were assessed in whole
      sediment and water-only systems. The results were combined with a bioenergetic
      based kinetic model of exposure pathways to account for the observed toxicity.
      The 10-d LC50 value based on the freely dissolved fraction was 9.3 times lower in
      spiked sediment (0.152 +/- 0.001 (95% CI) mg/L) than in water-only (1.390 +/-
      0.020 (95% CI) mg/L). Consequently, the actual 10-d LC50 value (208 mg/kg) was
      overestimated by the Equilibrium Partitioning calculation (1629 mg/kg). This
      suggests that the sediment associated LAS fraction was bioavailable to the
      snails. It could also be due to modifications in physiological parameters in
      absence of sediment, the organism natural substrate.

PMID- 19766367
TI  - Leaf phenolic compounds in red clover (Trifolium pratense L.) induced by exposure
      to moderately elevated ozone.
AB  - Red clover (Trifolium pratense L.), an important feed crop in many parts of the
      world, is exposed to elevated ozone over large areas. Plants can limit ozone
      induced damages by various defence mechanisms. In this work, changes in the
      concentrations of antioxidant phenolic compounds induced by slightly elevated
      levels of ozone were determined in red clover leaves by high-performance liquid
      chromatography and mass spectrometry. 31 different phenolics were identified and
      the most abundant isoflavones and flavonoids were biochanin A glycoside malonate
      (G-M), formononetin-G-M and quercetin-G-M. Elevated ozone (mean 32.4 ppb)
      increased the total phenolic content of leaves and also had minor effects on the
      concentrations of individual compounds. Elevated ozone increased the net
      photosynthesis rate of red clover leaves before visible injuries by 21-23%. This
      study thus suggests that the concentrations of phenolics in red clover leaves
      change in response to slightly elevated ozone levels.

PMID- 19766368
TI  - A new generation of women veterans: stressors faced by women deployed to Iraq and
      Afghanistan.
AB  - The extent of female service members' involvement in Operation Enduring Freedom
      (OEF) and Operation Iraqi Freedom (OIF), in terms of both the number of women
      deployed and the scope of their involvement, is unprecedented. While many of the
      mental health readjustment issues of female service members are likely to mirror
      those of the majority male Veteran population, this newest generation of women
      Veterans may also face unique threats to their mental health. The goal of this
      review it to highlight emerging issues relevant to the development of
      posttraumatic stress disorder (PTSD) among women deployed to Iraq and Afghanistan
      by reviewing the existing literature on gender-relevant issues among this cohort,
      as well as raising theoretically important issues that are worthy of further
      empirical investigation. Topics addressed include gender differences in combat
      experiences and in PTSD following combat exposure; sexual assault, sexual
      harassment and other interpersonal stressors experienced during deployment; women
      Veterans' experiences of premilitary trauma exposure; and unique stressors faced
      by women Veterans during the homecoming readjustment period. Given that most
      models of the impact of war zone deployment on PTSD are predicated on the
      experiences of male service members, women's expanding role in combat operations
      presents both an opportunity and a challenge to adapt these models to more
      effectively capture the experiences of female service members.

PMID- 19766369
TI  - The efficacy of short-term psychodynamic psychotherapy for depression: a meta
      analysis.
AB  - OBJECTIVES: It remains largely unclear, firstly whether short-term psychodynamic
      psychotherapy (STPP) is an effective treatment for depression, and secondly,
      which study, participant, or intervention characteristics may moderate treatment
      effects. The purpose of this study is to assess the efficacy of STPP for
      depression and to identify treatment moderators. RESULTS: After a thorough
      literature search, 23 studies totaling 1365 subjects were included. STPP was
      found to be significantly more effective than control conditions at post
      treatment (d=0.69). STPP pre-treatment to post-treatment changes in depression
      level were large (d=1.34), and these changes were maintained until 1-year follow
      up. Compared to other psychotherapies, a small but significant effect size (d=
      0.30) was found, indicating the superiority of other treatments immediately post
      treatment, but no significant differences were found at 3-month (d=-0.05) and 12
      month (d=-0.29) follow-up. Studies employing STPP in groups (d=0.83) found
      significantly lower pre-treatment to post-treatment effect sizes than studies
      using an individual format (d=1.48). Supportive and expressive STPP modes were
      found to be equally efficacious (d=1.36 and d=1.30, respectively). CONCLUSION: We
      found clear indications that STPP is effective in the treatment of depression in
      adults. Although more high-quality RCTs are necessary to assess the efficacy of
      the STPP variants, the current findings add to the evidence-base of STPP for
      depression.

PMID- 19766370
TI  - Responsibility and reflection: understanding our responses to perceived errors. A
      response to Woodward, Lemer and Wu.

PMID- 19766371
TI  - Recent advances in age-period-cohort analysis. A commentary on Dregan and
      Armstrong, and on Reither, Hauser and Yang.

PMID- 19766373
TI  - On the prospects for a blame-free medical culture.
AB  - Official policy-making bodies and experts in medical error have called for a
      shift in perspective to a blame-free culture within medicine, predicated on the
      basis that errors are largely attributable to systems rather than individuals.
      However, little is known about how the lived experience of blame in medical care
      relates to prospects for such a shift. In this essay we explore the benefits and
      costs of blame in medical culture. Our observations are informed by our clinical
      experience and supported by interview data from a study in which 163 American
      physicians were interviewed about caring for a total of 66 dying patients in two
      institutions. We observe three ways in which blame is invoked: (1) self-blame,
      (2) blame of impersonal forces or the "system," and (3) blame of others.
      Physicians articulate several important functions of blame: as a stimulus for
      learning and improvement; as a way to empathically allow physicians to forgive
      mistakes when others accept responsibility using self-blame; and as a way to
      achieve control over clinical outcomes. We argue that, since error is viewed as a
      personal failing and tends to evoke substantial self-blame, physicians do not
      tend to think of errors in a systems context. Given that physicians' ideology of
      self-blame is ingrained, accompanied by benefits, and limits a systems
      perspective on error, it may subvert attempts to establish a blame-free culture.

PMID- 19766372
TI  - Running to the store? The relationship between neighborhood environments and the
      risk of obesity.
AB  - We expand the search for modifiable features of neighborhood environments that
      alter obesity risk in two ways. First, we examine residents' access to
      neighborhood retail food options in combination with neighborhood features that
      facilitate physical activity. Second, we evaluate neighborhood features for both
      low income and non-low income neighborhoods (bottom quartile of median
      neighborhood income versus the top three quartiles). Our analyses use data from
      the Utah Population Database merged with U.S. Census data and Dun & Bradstreet
      business data for Salt Lake County, Utah. Linear regressions for BMI and logistic
      regressions for the likelihood of being obese are estimated using various
      measures of the individual's neighborhood food options and walkability features.
      As expected, walkability indicators of older neighborhoods and neighborhoods
      where a higher fraction of the population walks to work is related to a lower
      BMI/obesity risk, although the strength of the effects varies by neighborhood
      income. Surprisingly, the walkability indicator of neighborhoods with higher
      intersection density was linked to higher BMI/obesity risk. The expected inverse
      relationship between the walkability indicator of population density and
      BMI/obesity risk is found only in low income neighborhoods. We find a strong
      association between neighborhood retail food options and BMI/obesity risk with
      the magnitude of the effects again varying by neighborhood income. For
      individuals living in non-low income neighborhoods, having one or more
      convenience stores, full-service restaurants, or fast food restaurants is
      associated with reduced BMI/obesity risk, compared to having no neighborhood food
      outlets. The presence of at least one healthy grocery option in low income
      neighborhoods is also associated with a reduction in BMI/obesity risk relative to
      no food outlets. Finally, multiple food options within a neighborhood reduce
      BMI/obesity risk, relative to no food options, for individuals living in either
      low-income or non-low neighborhoods.

PMID- 19766374
TI  - Studying action representation in children via motor imagery.
AB  - The use of motor imagery is a widely used experimental paradigm for the study of
      cognitive aspects of action planning and control in adults. Furthermore, there
      are indications that motor imagery provides a window into the process of action
      representation. These notions complement internal model theory suggesting that
      such representations allow predictions (estimates) about the mapping of the self
      to parameters of the external world; processes that enable successful planning
      and execution of action. The ability to mentally represent action is important to
      the development of motor control. This paper presents a critical review of motor
      imagery research conducted with children (typically developing and special
      populations) with focus on its merits and possible shortcomings in studying
      action representation. Included in the review are age-related findings, possible
      brain structures involved, experimental paradigms, and recommendations for future
      work. The merits of this review are associated with the apparent increasing
      attraction for using and studying motor imagery to understand the developmental
      aspects of action processing in children.

PMID- 19766375
TI  - The perception of biological and mechanical motion in female fragile X
      premutation carriers.
AB  - Previous studies reported impaired visual information processing in patients with
      fragile X syndrome and in premutation carriers. In this study, we assessed the
      perception of biological motion (a walking point-light character) and mechanical
      motion (a rotating shape) in 25 female fragile X premutation carriers and in 20
      healthy non-carrier controls. Stimuli were moving stimulus dots embedded among a
      cloud of noise dots. Sensitivity (d') for motion detection was determined.
      Emotional symptoms were assessed by Hamilton's depression and anxiety rating
      scales. Results revealed that the premutation carriers displayed lower
      sensitivities for biological and mechanical motion relative to the non-carriers.
      This deficit was more pronounced in the case of biological stimuli. The
      premutation carriers displayed higher depression and anxiety scores relative to
      the non-carriers. Higher depression, but not anxiety, scores were associated with
      decreased sensitivity for biological, but not mechanical, motion in the carrier
      group. These results suggest that motion perception deficits are detectable in
      fragile X premutation carriers, and that the impairment of biological motion
      perception is associated with depressive symptoms.

PMID- 19766376
TI  - Time needed for a regional emergency medical system to implement resuscitation
      Guidelines 2005--The Netherlands experience.
AB  - INTRODUCTION: In December 2005, updated resuscitation Guidelines (G) were
      introduced worldwide and will be revised again in 2010. This study sought to
      elucidate how long it takes to implement new guidelines. METHODS: This was a
      prospective observational study. From July 2005 to January 2008, we included all
      patients with an out-of-hospital cardiac arrest of suspected cardiac cause. We
      analyzed Emergency Medical System (EMS) Guideline usage via defibrillator
      recordings of the continuous ECG and impedance signals. We excluded patients with
      missing or otherwise unusable ECGs. All shocks and CPR cycles were individually
      classified. The same Guideline needed to be applied for at least 75% of all
      shocks and CPR cycles. If no shocks had been given, continuous ECGs were
      classified by its CPR status only. Continuous ECGs were classified as G1992,
      G2000 or G2005. If at least 75% of the shocks were given according to G2000 and
      at least 75% of the CPR was according to G2005, the Guideline protocol was
      classified as intermediate. All analyses that did not fulfil any Guideline
      criteria were classified as indeterminate. RESULTS: Of 1672 analyzable
      resuscitations, 31 (2%) used G1992, 826 (49%) G2000, 608 (36%) G2005, and 125
      (7%) intermediate Guidelines. The Guideline protocol could not be identified for
      the remaining 81 (5%) patients. It took 17 months (from publication) until EMS
      personnel applied GL2005 in over 80% of cases. CONCLUSION: Our experience shows
      it took one-and-a-half years to effectively implement new resuscitation
      Guidelines. We believe improvements in implementation can shorten this to six
      months.

PMID- 19766377
TI  - Factors influencing delivery mode for nulliparous women with a singleton
      pregnancy and cephalic presentation during a 17-year period.
AB  - OBJECTIVE: To evaluate the effects of maternal age, induction of labour, epidural
      analgesia and birth weight on mode of delivery in nulliparous women with a
      singleton pregnancy and cephalic presentation at > or =36 weeks gestation, and to
      describe how these factors and their influence have changed over a 17-year period
      from 1989 to 2005. STUDY DESIGN: The study was conducted in the obstetric
      department of a university teaching hospital in Ireland. Of 45,647 women
      delivered, 14,867 were nulliparous with a singleton pregnancy and cephalic
      presentation and undergoing labour at > or =36 weeks gestation, and were included
      in the study. The main outcome measures were the influence of maternal age,
      induction of labour, epidural analgesia and birth weight on the mode of delivery.
      Multinomial logistic regression analysis for type of delivery and the associated
      explanatory variables and trend analysis of these variables were performed.
      RESULTS: There was a significant progressive increase in both unplanned abdominal
      delivery and instrumental vaginal delivery, with advancing maternal age.
      Induction of labour increased the risk of unplanned abdominal delivery (OR 1.92;
      95% CI 1.73-2.14). Epidural analgesia was associated with an increased risk of
      instrumental vaginal delivery (OR 4.68; 95% CI 4.18-5.25), and unplanned
      abdominal delivery (OR 2.29; 95% CI 1.98-2.66). Mothers of infants with birth
      weight > or =4.5 kg were less likely to be delivered by instrumental vaginal
      delivery (OR 0.60; 95% CI 0.41-0.88), than mothers delivering infants in the 2.50
      4.49 kg birth weight category. Between 1989 and 2005 there was a significant
      increase in maternal age (P=0.0001), birth weight (P=0.042) and unplanned
      abdominal delivery rates (P=0.0004), and a reduction in instrumental vaginal
      delivery rates (P=0.0013). CONCLUSIONS: These data demonstrate that the
      increasing trend of unplanned abdominal delivery in nulliparous women with a
      singleton pregnancy and cephalic presentation may be partially explained by
      advancing maternal age, and other obstetric factors also play a significant role.

PMID- 19766378
TI  - Urinary ascites following caesarean section: an unusual presentation of bladder
      injury.

PMID- 19766379
TI  - Ultrasound guided laser embryonic reduction of dichorionic triplets in
      dichorionic twins.

PMID- 19766380
TI  - Plasma sterilization of poly lactic acid ultrasound contrast agents: surface
      modification and implications for drug delivery.
AB  - Poly lactic acid (PLA) ultrasound contrast agents (CA) have been developed
      previously in our laboratory for ultrasound (US) imaging, as well as surface
      coated with doxorubicin to create a potential targeted platform of
      chemotherapeutic delivery using focused US. However, we have previously found it
      impossible to sterilize these agents while at the same time maintaining their
      acoustic properties, a task that would probably require fabrication within a
      clean facility. The purpose of this paper is to investigate the feasibility of
      using plasma to sterilize these CA while maintaining maximum echogenicity, a step
      that would greatly facilitate in vivo investigations. Effects of plasma exposure
      time (1, 3 and 6 min) and intensity (low-10 mA, 6.8 W; medium-15 mA, 10.5 W; and
      high-25 mA, 18 W) on the CAs' acoustic properties, surface morphology, zeta
      potential, capacity to carry chemotherapeutics and overall sterility are
      described. Both increases in plasma intensity and exposure time increased CA zeta
      potential and also significantly increased drug payload. High-intensity plasma
      exposure for 3 min was found to be an optimal sterilization protocol for maximal
      (100%) preservation of CA echogenicity. Plasma exposure resulted in sterile
      samples and maintained original CA enhancement of 20 dB and acoustic half-life
      over 75 min, while increasing CA zeta potential by 11 mV and doxorubicin loading
      efficiency by 10%. This study not only shows how a highly temperature- and
      pressure-sensitive agent can be sterilized using plasma, but also that surface
      modification can be used to increase surface binding of the drug.

PMID- 19766381
TI  - Ultrasound and microbubble-induced intra- and intercellular bioeffects in primary
      endothelial cells.
AB  - Recent developments in the field of ultrasound (US) contrast agents have
      demonstrated that these encapsulated microbubbles can not only be used for
      diagnostic imaging but may also be employed as therapeutic carriers for
      localized, targeted drug or gene delivery. The exact mechanisms behind increased
      uptake of therapeutic compounds by US-exposed microbubbles are still not fully
      understood. Therefore, we studied the effects of stably oscillating SonoVue
      microbubbles on relevant parameters of cellular and intercellular permeability,
      i.e., reactive oxygen species (ROS) homeostasis, calcium permeability, F-actin
      cytoskeleton, monolayer integrity and cell viability using live-cell fluorescence
      microscopy. US was applied at 1-MHz, 0.1MPa peak-negative pressure, 0.2% duty
      cycle and 20Hz pulse repetition frequency to primary endothelial cells. We
      demonstrated increased membrane permeability for calcium ions, with an important
      role for H(2)O(2). Catalase, an extracellular H(2)O(2) scavenger, significantly
      blocked the influx of calcium ions. Further changes in ROS homeostasis involved
      an increase in intracellular H(2)O(2) levels, protein nitrosylation and a
      decrease in total endogenous glutathione levels. In addition, an increase in the
      number of F-actin stress fibers and F-actin cytoskeletal rearrangement were
      observed. Furthermore, US-exposed microbubbles significantly affected endothelial
      monolayer integrity, but importantly, disrupted cell-cell interactions were
      restored within 30min. Finally, cell viability was not affected. In conclusion,
      these data provide more insight in the interactions between US, microbubbles and
      endothelial cells, which is important for understanding the mechanisms behind US
      and microbubble-enhanced uptake of drugs or genes.

PMID- 19766382
TI  - Evaluation of bone-tendon junction healing using water jet ultrasound indentation
      method.
AB  - The re-establishment of bone-tendon junction (BTJ) tissues with the junction,
      characterized as a unique transitional fibrocartilage zone, is involved in many
      trauma and reconstructive surgeries. Experimental and clinical findings have
      shown that a direct BTJ repair requires a long period of immobilization, which
      may be associated with a postoperative weak knee. Therefore, it is necessary to
      evaluate the morphologic and mechanical properties of BTJ tissues in situ to
      better understand the healing process for the purpose of reducing the adverse
      effects of immobilization. We previously reported a noncontact ultrasound water
      jet indentation system for measuring and mapping tissue mechanical properties.
      The key idea was to utilize a water jet as an indenter as well as the coupling
      medium for high-frequency ultrasound. In this article, we used ultrasound water
      jet indentation to evaluate the BTJ healing process. The system's capability of
      measuring the material elastic modulus was first validated using tissue-mimicking
      phantoms. Then it was employed to assess the healing of the BTJ tissues after
      partial patellectomy over time on twelve 18-week-old female New Zealand White
      rabbits. It was found that in comparison with the normal control samples, the
      elastic modulus of the fibrocartilage of the postoperative samples was
      significantly smaller, while its thickness increased significantly. Among the
      postoperative sample groups, the elastic modulus of the fibrocartilage of the
      samples harvested at week 18 was significantly higher than those harvested at
      week 6 and week 12, which was even comparable with the value of the control
      samples at the same sacrifice time. The results suggested that the noncontact
      ultrasound water jet indentation system provided a nondestructive way to evaluate
      the material properties of small animal tissues in situ and thus had the ability
      to evaluate the healing process of BTJ.

PMID- 19766383
TI  - Editorial comment on: characteristics and outcomes of patients with clinical T1
      grade 3 urothelial carcinoma treated with radical cystectomy: results from an
      international cohort.

PMID- 19766384
TI  - Characteristics and outcomes of patients with clinical T1 grade 3 urothelial
      carcinoma treated with radical cystectomy: results from an international cohort.
AB  - BACKGROUND: Management of T1 grade 3 (T1G3) urothelial carcinoma of the bladder
      (UCB), with its variable behaviour, represents one of the most difficult
      challenges for urologists and patients alike. OBJECTIVE: To evaluate the
      characteristics and long-term outcome of patients with clinical T1G3 UCB treated
      with radical cystectomy (RC). DESIGN, SETTING, AND PARTICIPANTS: Data from 1136
      patients treated with RC for clinical T1G3 UCB without neoadjuvant chemotherapy
      were collected at 12 centres located in Europe, the United States, and Canada.
      Median age was 67 yr (range: 29-94), with a male-to-female ratio of 4:1.
      MEASUREMENTS: Patients' characteristics and outcome are evaluated. RESULTS AND
      LIMITATIONS: Of the 1136 patients, 33.4% had non-organ-confined stage at
      cystectomy, and 16.2% had lymph node (LN) metastasis; 49.7% were upstaged after
      RC to muscle-invasive disease, while 21.4% were downstaged to lower than T1G3.
      Within a median follow-up of 48 mo, 35.5% of patients died of metastatic UCB.
      CONCLUSIONS: Approximately half of the patients treated with RC without
      neoadjuvant chemotherapy for clinical T1G3 UCB are upstaged to muscle-invasive
      UCB. These rates support the inadequacy of clinical decision making based on
      current treatment paradigms and staging tools. Therefore, identification of
      patients with clinical T1G3 disease at high risk of disease progression is of the
      utmost importance, as these patients are likely to benefit from early RC.

PMID- 19766385
TI  - Re: Mariarosaria Bucci, Vincenzo Mirone, Annarita Di Lorenzo, et al. Hydrogen
      sulphide is involved in testosterone vascular effect. Eur Urol 2009;56:378-84.

PMID- 19766386
TI  - Feasibility of T-cell-based adoptive immunotherapy in the first 12 patients with
      advanced urothelial urinary bladder cancer. Preliminary data on a new immunologic
      treatment based on the sentinel node concept.
AB  - BACKGROUND: Expected 2-yr survival for patients with urothelial urinary bladder
      cancer (UBC) with lymph node involvement (pN2) is 20%, regardless of standard
      neoadjuvant/adjuvant oncologic treatment. Tumor-reactive lymphocytes are present
      in sentinel nodes (SNs) draining human bladder cancer and display immunologic
      function on restimulation in vitro. Metinel nodes (MNs) drain secondarily from
      metastatic tumors and also possess tumor-reactive lymphocytes, which might be a
      source for adoptive T-cell immunotherapy. OBJECTIVES: To determine if MN
      detection and subsequent expansion of autologous T-helper cells with subsequent
      reinfusion was feasible and safe to perform in patients with metastatic UBC.
      DESIGN, SETTING, AND PARTICIPANTS: In an open trial, the first 12 included
      patients are described. Patients were prospectively selected from a single
      tertiary academic center and had metastatic UBC. All 12 patients were
      preoperatively staged as T2-T4b N1-2 and/or M0-M1 or MX. INTERVENTIONS: MNs were
      excised in conjunction with intended cystectomy. T lymphocytes were extracted
      with enhancement and expansion of tumor specific T-helper cells, followed by
      reinfusion of expanded T cells. MEASUREMENTS: All patients were preoperatively
      staged with transurethral resection of the bladder and routine computed
      tomography scan. Intended detection of MNs was performed intraoperatively with
      intended cystectomy. Harvested T cells were evaluated and cell cultures were
      established. Assessment of reinfusion of expanded, autologous, tumor-specific T
      helper cells to six of the patients was performed, focusing on adverse effects.
      RESULTS AND LIMITATIONS: In six patients, it was feasible to administer the
      treatment. Reinfusion of these T cells was performed without any major adverse
      effects. In six other patients, we encountered technical failures. CONCLUSIONS: A
      novel adoptive immunotherapy based on T cells from tumor-draining lymph nodes is
      feasible in advanced UBC. Infusion of expanded, autologous, tumor-specific T
      helper cells might be a future treatment option in metastasized UBC. Long-term
      overall survival remains to be determined.

PMID- 19766387
TI  - Does glycated hemoglobin have clinical significance in ischemic stroke patients?
AB  - OBJECTIVES: It has been suggested that patients with an elevated hemoglobin A1c
      (HbA1c) level have an increased risk of cardiovascular disease regardless of the
      presence of diabetes. However, an association between HbA1c and stroke has not
      yet been determined. In this study, our purpose was to examine whether HbA1c was
      independently associated with various types of cerebral vascular lesions in
      stroke patients. METHODS: A consecutive series of acute ischemic stroke patients
      were included for this analysis from October, 2002, to March, 2006. HbA1c was
      examined on admission, and MR imaging was performed for analysis of large artery
      diseases (LADs) and small artery diseases (SADs). Symptomatic or asymptomatic LAD
      was diagnosed by MR angiography, and SAD was classified as leukoaraiosis,
      microbleeds, or old lacunar infarctions. RESULTS: A total of 639 stroke patients
      were analyzed (diabetics, n=247; non-diabetics, n=392). There was no relationship
      between the level of HbA1c and any type of cerebrovascular lesion in the non
      diabetic patients. In contrast, HbA1c showed a significant negative association
      with symptomatic LAD and leukoaraiosis in the diabetic patients using univariate
      analysis (p=0.01 and p<0.05, respectively). These associations did not remain
      significant, however, after adjustment for age and hypertension. This was, in
      part, because the HbA1c level in our diabetic population decreased gradually with
      age (p=0.03). CONCLUSIONS: Our results indicate that HbA1c is not associated with
      risk for various types of cerebrovascular lesions in ischemic stroke patients.
      The negative association between age and HbA1c in diabetic patients should be
      further investigated.

PMID- 19766388
TI  - Removal of nickel from electroplating rinse waters using electrostatic shielding
      electrodialysis/electrodeionization.
AB  - Electrostatic shielding zones made of electrode graphite powder were used as a
      new type of ionic and electronic current sinks. Because of the local elimination
      of the applied electric field, voltage and current within the zones, ions are led
      inside them and accumulate there. The current sinks were implemented in
      electrostatic shielding electrodialysis of a simulated nickel plating rinse water
      containing 100 mg L(-1) nickel and electrodeionization of a 0.001 M NiSO(4)
      solution with simultaneous electrochemical regeneration of the ion exchange resin
      beds. Pure water was obtained with a Ni(2+) ion concentration of less than 0.1 mg
      L(-1) at a flow rate of 2.02 x 10(-4)dm(3)s(-1) diluate stream and a current
      density of 30 Am(-2).

PMID- 19766389
TI  - Factors influencing arsenic and nitrate removal from drinking water in a
      continuous flow electrocoagulation (EC) process.
AB  - An experimental study was conducted under continuous flow conditions to evaluate
      some of the factors influencing contaminant removal by electrocoagulation (EC). A
      bench-scale simulation of drinking water treatment was done by adding a
      filtration column after a rectangular EC reactor. Contaminant removal efficiency
      was determined for voltages ranging from 10 to 25 V and a comparative study was
      done with distilled water and tap water for two contaminants: nitrate and
      arsenic(V). Maximum removal efficiency was 84% for nitrate at 25 V and 75% for
      arsenic(V) at 20 V. No significant difference in contaminant removal was observed
      in tap water versus distilled water. Increase in initial As(V) concentration from
      1 ppm to 2 ppm resulted in a 10% increase in removal efficiency. Turbidity in the
      EC reactor effluent was 52 NTU and had to be filtered to achieve acceptable
      levels of final turbidity (5 NTU) at steady-state. The flow regime in the
      continuous flow reactor was also evaluated in a tracer study to determine whether
      it is a plug flow reactor (PFR) or constantly stirred tank reactor (CSTR) and the
      results show that this reactor was close to an ideal CSTR, i.e., it was fairly
      well-mixed.

PMID- 19766390
TI  - Sorption of copper(II) onto super-adsorbent of bentonite-polyacrylamide
      composites.
AB  - In this work, bentonite embedded in the polyacrylamide (PAAm) gels was used as a
      novel adsorbent for the removal of Cu(II) from aqueous solution. The sorption and
      desorption of Cu(II) on bentonite-polyacrylamide (BENT-PAAm) was investigated as
      the function of pH, ionic strength, adsorbent content, Cu(II) concentrations and
      temperature. The results indicated that the sorption of Cu(II) on BENT-PAAm was
      strongly dependent on pH, ionic strength and temperature. The sorption increased
      from about 9% to 97% at pH ranging from 2.4 to 7. The sorption of Cu(II) on BENT
      PAAm increased with increasing temperature and decreasing ionic strength. The
      sorption of Cu(II) on BENT and on BENT-PAAm was an endothermic and irreversible
      process. The results of desorption indicated that the adsorbed Cu(II) ions on
      solid particles were difficult to be desorbed from solid to liquid phase. From
      the comparison with BENT, BENT-PAAm showed higher sorption capacity with C(smax)
      increasing from 29 to 33 mg/g at pH 6.2 and from 11 to 20mg/g at pH 5.0 for the
      sorption of Cu(II) from BENT to BENT-PAAm composites. The average standard
      enthalpy change (Delta H degrees) and the entropy change (DeltaS degrees ) of
      Cu(II) sorption on BENT-PAAm are higher than those of Cu(II) sorption on BENT.
      The BENT-PAAm composites can be used as a super-adsorbent for the removal of
      Cu(II) from aqueous solution.

PMID- 19766391
TI  - Adsorption intrinsic kinetics and isotherms of lead ions on steel slag.
AB  - Batch experiments were carried out to investigate the kinetics of adsorption of
      lead ions by steel slag on the basis of the external diffusion, intra-particle
      diffusion and adsorption reaction model (pseudo-first-order, pseudo-second
      order). The results showed that the controlling step for the adsorption kinetics
      changed with the varying experimental parameters. When the particle size of steel
      slag was larger than 120 mesh, intra-particle diffusion of Pb(2+) was the
      controlling step, and when the initial concentration of Pb(2+) was less than 150
      m gL(-1) or the shaking rate was lower than 150 rpm, external diffusion of Pb(2+)
      was promoted. Contrary to the former experimental conditions the adsorption
      reaction was the controlling step, and the adsorption followed second-order
      kinetics, with an adsorption rate constant of 13.26 g mg(-1)min(-1). The
      adsorption isotherm of Pb(2+) with steel slag followed the Langmuir model, with a
      correlation coefficient of 0.99.

PMID- 19766392
TI  - Clinical and endocrinological changes after electro-acupuncture treatment in
      patients with osteoarthritis of the knee.
AB  - Neurobiological mechanisms invoking the release of endogenous opioids and
      depression of stress hormone release are believed to be the basis of acupuncture
      analgesia. This study compared plasma beta-endorphin and cortisol levels with
      self assessment scores of intensity of pain, before and after 10 days of electro
      acupuncture treatment in patients suffering from chronic pain as a result of
      osteoarthritis knees. Forty patients of either sex over 40 years with primary
      osteoarthritis knee were recruited into a single-blinded, sham-controlled study.
      For electro-acupuncture group the points were selected according to the
      Traditional Chinese Medicine Meridian Theory. In the sham group needles were
      inserted at random points away from true acupoints and no current was passed.
      Both groups were treated for 10 days with one session every day lasting for 20
      25min. Pre- and post-treatment Western Ontario and McMaster Universities (WOMAC)
      index of osteoarthritis knee and Visual Analogue Scale (VAS) for pain were
      recorded and blood samples were taken for the measurement of plasma cortisol and
      beta-endorphin levels. Following electro-acupuncture treatment there was a
      significant improvement in WOMAC index and VAS (p=0.001), a significant rise in
      plasma beta-endorphin (p=0.001), and a significant fall in plasma cortisol
      (p=0.016). In conclusion electro-acupuncture resulted in an improvement in pain,
      stiffness and disability. Of clinical importance is that an improvement in
      objective measures of pain and stress/pain associated biomarkers was shown above
      that of a sham treatment; hence demonstrating acupuncture associated
      physiological changes beyond that of the placebo effects.

PMID- 19766393
TI  - The analgesic action of topical diclofenac may be mediated through peripheral
      NMDA receptor antagonism.
AB  - The analgesic mechanism underlying the efficacy of topical diclofenac in the
      treatment of musculoskeletal pain is incompletely understood. The present study
      investigated whether intramuscular injection of diclofenac (0.1mg/ml,
      approximately 340microM) could attenuate jaw-closer muscle nociceptor discharge
      and mechanical sensitization induced by activation of peripheral 5
      hydroxytryptamine (serotonin) or excitatory amino acid receptors in anesthetized
      Sprague-Dawley rats. Diclofenac inhibited nociceptor discharge evoked by NMDA,
      but had no effect on nociceptor discharge evoked by 5-hydroxytryptamine or AMPA.
      Subsequent experiments revealed that diclofenac-mediated inhibition of NMDA
      evoked nociceptor discharge was competitive. Intramuscular injection of 5
      hydroxytryptamine, NMDA and AMPA also decreased nociceptor mechanical threshold,
      however, only the mechanical sensitization produced by NMDA was reversed by
      diclofenac. Co-administration of the proinflammatory prostaglandin PGE(2) did not
      alter the ability of diclofenac to significantly attenuate NMDA-evoked nociceptor
      discharge or NMDA-induced mechanical sensitization. Intramuscular injection of
      either diclofenac or the competitive NMDA receptor antagonist DL-2-amino-5
      phosphonovalerate (50mM) alone could elevate nociceptor mechanical threshold for
      a 30min period post-injection. The present study indicates that in vivo,
      diclofenac can exert a selective, competitive inhibition of peripheral NMDA
      receptors at muscle concentrations achievable after topical administration of
      diclofenac containing preparations. This property may contribute to the analgesic
      effect of topical diclofenac when used for muscle pain.

PMID- 19766394
TI  - Balancing nociception in cycling females.

PMID- 19766395
TI  - Effects of unpredictable stimulation on pain and nociception across the cardiac
      cycle.
AB  - Previous research has demonstrated that the nociceptive flexion reflex (NFR) and
      pain-related evoked potentials are reduced in amplitude when elicited during the
      middle of the cardiac cycle. Despite these findings, suggesting a baroreceptor
      mechanism of antinociception during systole, pain intensity ratings reported in
      these studies were not modulated across the cardiac cycle. This discrepancy
      between the neurophysiological correlates of pain and its subjective experience
      was the focus of the current study that used a mixed block design to assess the
      effects of natural arterial baroreceptor activity on both the NFR and pain
      intensity and unpleasantness reports. Specifically, electrocutaneous stimuli were
      randomly delivered to the sural nerve at one of five intensities (50% pain
      threshold, 75% pain threshold, pain threshold, midway between pain threshold and
      pain tolerance, pain tolerance) at five intervals (0, 150, 300, 450, and 600ms)
      after the R-wave of the electrocardiogram. Under painful stimulation, intensity
      and unpleasantness varied in a quadratic manner across the cardiac cycle; pain
      was highest at R+300ms and lowest at R+0 and R+600ms. Under non-painful
      stimulation, ratings declined linearly as the cycle progressed. Finally,
      nociceptive responses did not differ among the R-wave to stimulation intervals
      for both painful and non-painful intensities. The observed phasic modulation of
      pain may be explained by a central nervous system alarm/defence reaction
      triggered by the unpredictability of the potentially damaging stimulation. The
      absence of systolic attenuation of nociceptive responding is compatible with
      previous evidence that baroreceptor modulation of the NFR is abolished under
      conditions of heightened arousal.

PMID- 19766396
TI  - Lorentz microscopy mapping for domain wall structure study in L1(0) FePd thin
      films.
AB  - Thin film alloys with perpendicular anisotropy were studied using Lorentz
      transmission electron microscopy (LTEM). This work focuses on the configuration
      of domain walls and demonstrates the suitability and accuracy of LTEM for the
      magnetic characterization of perpendicular magnetic anisotropy materials. Thin
      films of chemically ordered (L1(0)) FePd alloys were investigated by micro
      magnetic modeling and LTEM phase retrieval approach. The different components of
      magnetization described by the modeling were studied on experimental images and
      confirmed by LTEM contrast simulation. Furthermore, quantitative measurements of
      magnetic induction inside the domain walls were made by using an original method
      to separate the electrical and magnetical contributions to the phase information.
      Irregularities were also observed along the domain walls which could play a major
      role during the magnetization processes.

PMID- 19766397
TI  - Epidemiology of paediatric burn injuries in Hamadan, Iran.
AB  - Burn injuries are prevalent worldwide, especially in developing countries; and
      they are significant paediatric injuries in Iran. This study was performed to
      analyse the epidemiology and aetiology of paediatric burns in Hamadan province in
      the west part of Iran from March 2004 to March 2007. The incidence rate of child
      hospitalisation for burns was 33.4 per 100,000 person-years. The median age was 3
      years with 69% of the patients under 4 years. The male-to-female ratio of
      incidence rate for all age groups was 1.52. Scald was the leading cause in almost
      all age groups and caused 266 (71.7%) burns. Correlation analysis showed that
      younger children are more vulnerable to scald injury. The mean body surface area
      (BSA) of burns was 16.36 (SD=11.42) in all cases. Flame was more fatal than other
      causes of burns. The total fatality rate in this study was 3.5%. Epidemiological
      findings reveal that scald, age, gender and residence in rural area are the major
      issues that should be discussed in considering childhood burns. Prevention
      efforts should focus on the reduction of scald injuries during food preparation
      or hot liquid spillage. These efforts should target rural infants, toddlers and
      boys.

PMID- 19766398
TI  - Assessment of the relation between prealbumin serum level and healing of skin
      grafted burn wounds.
AB  - Nutritional status is an important factor in graft healing. Prealbumin
      (transthyretin) is a better nutritional marker than the widely used albumin serum
      level. Prealbumin serum levels were estimated in an endeavour to correlate them
      to graft healing and to serve as a predictor of graft healing in burn wounds.
      Fifty burned patients undergoing graft in the Suez Canal University Hospital Burn
      Unit were subjected to this cross-sectional study. Prealbumin levels were
      assessed on preoperative day and on the fourth postoperative day. Graft healing
      was considered complete when the take was 90% or more of the grafted area. The
      most significantly correlated factor to graft healing was serum prealbumin. Serum
      albumin levels were not in significant correlation with graft healing or
      prealbumin levels. In addition, serum prealbumin levels were significantly higher
      in the younger age group and significantly lower in patients with chronic
      diseases. Serum prealbumin level is a sensitive tool in predicting graft take in
      burned patients when all local conditions are favourable and optimised.
      Nevertheless, it seems less sensitive in the prediction of graft healing in small
      raw areas less than 5% of total body surface area (TBSA).

PMID- 19766399
TI  - Comparison of efficacy of silicone gel, silicone gel sheeting, and topical onion
      extract including heparin and allantoin for the treatment of postburn
      hypertrophic scars.
AB  - We compared the efficacy of silicone gel (Scarfade), silicone gel sheet (Epi
      Derm), and topical onion extract including heparin and allantoin (Contractubex)
      for the treatment of hypertrophic scars. Forty-five postburn scars were included
      in the study. Patients with scars less than 6 months from injury were assigned at
      random to three groups each containing 15 scars, and their treatment was
      continued for 6 months. Scars were treated with Scarfade, Epiderm and
      Contractubex. Scar assessment was performed at the beginning of the treatment,
      and at the end of the sixth month when the treatment was completed by using the
      Vancouver scar scale. The difference between before and after treatment scores
      for each three groups was statistically significant. The difference between
      Scarfade group and Epi-Derm group was not significant; however, the differences
      of the other groups (Scarfade-Contractubex, Epiderm-Contractubex) were
      significant. Silicone products, either in gel or sheet, are superior to
      Contractubex in the treatment of the hypertrophic scar. The therapist should
      select the most appropriate agent according to the patient's need and guidelines
      of these signs.

PMID- 19766400
TI  - Is HBOT treatment effective in recovering zone of stasis? An experimental
      immunohistochemical study.
AB  - Studies aimed at recovering the zone of stasis are one of the major issues of
      experimental burn studies. Hypoxia and oedema at that zone may cause irreversible
      changes. Due to anti-oedematous and antihypoxic effects of hyperbaric oxygen
      treatment (HBOT), it may be beneficial in recovering the zone of stasis. We
      performed an experimental study using 20 Sprague-Dawley rats, each weighing 350
      450 g. The rats were first divided into two groups as 24h and 5 days.
      Subsequently, control and treatment groups (five rats in each group) were formed.
      For burn wounds, we used the burn comb model, which was described by Regas and
      Ehrlich. In the treatment group, 2.5 ATA HBOT was applied for 90 min twice daily.
      A 0.8-cm punch biopsy was performed and samples for histological examination were
      taken from the centre of burn area. The rats were sacrificed by administering '3
      mci technetium-99m methoxy butyl nitrite' ((99)Tc(m) MIBI) through the femoral
      vein. Biopsy materials were evaluated by histological and immunohistochemical
      methods. Dorsal skin fragment, excised to 1cm margin, was imaged by scintigraphic
      measurements with a gamma camera. Wet and dry weight measurements of excised skin
      fragments were taken. As a result, HBOT showed a positive effect at the cellular
      level in the first 24h. It increased recovery potential by augmenting
      neovascularisation and decreasing oedema in the 5-day group.

PMID- 19766401
TI  - Toxic epidermal necrolysis (Lyell's disease).
AB  - Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe
      adverse drug reactions, characterized by a low incidence but high mortality,
      initially described as separate entities, but today considered variants of the
      same pathologic process and differing only for severity. The majority of cases
      appear to be related to idiosyncratic drug reactions. The drugs most commonly
      involved are: antibiotics such as sulfonamides, beta-lactam, tetracyclines and
      quinolones; anticonvulsants such as phenytoin, phenobarbital and carbamazapine;
      antiretroviral drugs; nonsteroidal anti-inflammatory drugs, allopurinol. There is
      common agreement to consider TEN as the manifestation of a disregulated immune
      reaction against epithelial cells. During the first stages of TEN, apoptosis
      mediates keratinocyte death and the pivotal role of Fas-FasL pathway activation
      during TEN is undoubted. T cell cytotoxicity, demonstrated during TEN, has been
      shown to be mediated by the perforin-granzyme pathway. It seems, also, clear that
      a peculiar cytokine pattern plays an important role in TEN pathogenesis. The
      cutaneous findings result in an acute macular erythematous rash with bullae.
      These lesions rapidly exhibit Nikolsky's sign and a separation of large sheets of
      epidermis from the dermis and a subsequent localised shedding develops rapidly,
      which can become very extensive. When feasible, admission in burn or intensive
      care unit, positioning the patients in air-fluidised beds, is universally
      considered crucial in TEN treatment. The prompt withdrawal of the suspected drug,
      fluid and electrolyte replacement and topical wound care are the first line of
      therapy. The use of corticosteroids has been abandoned and the role of
      immunosuppressants, despite some success, is not well defined and is not
      considered as a standard. A trial comparing thalidomide versus placebo in TEN
      patients was suspended because mortality rate increased in the treated group.
      Infliximab, a chimeric monoclonal antibody to TNF-alpha, has been administered to
      a patient, in single infusion, with a favourable outcome. Plasmapheresis is
      reported to lead to some success in TEN treatment, with improvement of clinical
      conditions and high percentage of survival. Different authors reported good
      results in terms of decreasing mortality and morbidity or improving clinical
      conditions of the use of human intravenous immunoglobulins (IVIGs). Regardless,
      the true utility of this treatment remains controversial. In 2005, the authors
      (ML and RC), dealing with a number of severe TEN cases, proposed a new protocol
      based on the combination of these last two techniques reporting their preliminary
      results in the treatment of severe TEN patients.

PMID- 19766402
TI  - Regulation of cortical and hippocampal 5-HT(1A) receptor function by
      corticosterone in GR+/- mice.
AB  - Our objective in the present study was to examine 5-HT(1A) receptor function in
      prefrontal cortex and hippocampus of GR+/- mice, which appear to be an
      appropriate murine model of depression. 5-HT(1A) receptor function was determined
      by measuring [(35)S]GTPgammaS binding stimulated by the 5-HT(1A) receptor agonist
      8-OH-DPAT (1 microM), an indication of the capacity of the receptor to activate G
      proteins. 5-HT(1A) receptor expression was determined by measuring the binding of
      [(3)H]8-OH-DPAT (2 nM). We observed no effect of the constitutive reduction in GR
      on 5-HT(1A) receptor-stimulated [(35)S]GTPgammaS binding or 5-HT(1A) receptor
      binding sites. Corticosterone treatment (10mg/kg, sc once daily for 21 days) of
      wild-type mice resulted in a decrease in 5-HT(1A) receptor function in prefrontal
      cortex [8-OH-DPAT-stimulated [(35)S]GTPgammaS binding (% above basal), vehicle
      treated: 39+/-4.9; corticosterone-treated: 17+/-2.8], but not in hippocampus. The
      constitutive reduction in GR expression prevented the down-regulation of 5-HT(1A)
      receptor function in frontal cortex by chronic corticosterone administration. In
      contrast, corticosterone treatment of GR+/- mice resulted in an increase in 5
      HT(1A) receptor function in hippocampus which reached statistical significance in
      CA2/3 region [8-OH-DPAT-stimulated [(35)S]GTPgammaS binding (% above basal),
      vehicle-treated: 41+/-9.7; corticosterone-treated: 94+/-23]. These changes seem
      to be evoked by a combined effect of high corticosterone levels and GR
      deficiency. Although GR+/- mice do not exhibit changes in baseline
      corticosterone, the constitutive deficiency in GR appears to have unmasked
      regulatory effects of elevated corticosterone in the maintenance of 5-HT(1A)
      receptor function in prefrontal cortex and hippocampus.

PMID- 19766403
TI  - Low early morning plasma cortisol in posttraumatic stress disorder is associated
      with co-morbid depression but not with enhanced glucocorticoid feedback
      inhibition.
AB  - BACKGROUND: Co-morbid major depressive disorder (MDD) in individuals with
      posttraumatic stress disorder (PTSD) confers a more severe clinical course and is
      associated with distinct biologic abnormalities. Although dysregulation in the
      hypothalamic pituitary adrenal (HPA) axis has been well established in PTSD, the
      impact of commonly co-occuring MDD has received scant attention. METHODS:
      Overnight (7p.m. to 7a.m.) plasma cortisol, adrenocorticotropic hormone (ACTH),
      dehydroepiandrosterone sulphate (DHEA-S) were measured at 30 min intervals in 9
      participants with PTSD with MDD (PTSD+MDD), 9 with PTSD without MDD (PTSD-MDD)
      and 16 non-traumatized healthy controls. A low-dose dexamethasone suppression
      test was administered to evaluate feedback sensitivity to glucocorticoids. Linear
      mixed models with body mass index (BMI) and age as covariates and Bonferroni
      corrected post hoc tests assessed group differences. RESULTS: Compared to healthy
      controls, subjects with PTSD+MDD, but not those subjects with PTSD-MDD, exhibited
      lower basal plasma cortisol levels between 1:30 a.m. and 3:30 a.m. and at 4:30
      a.m. and 6:30 a.m. (effect size d=0.75). Despite similar plasma ACTH levels
      between the three groups, the ACTH/cortisol ratio was higher in PTSD+MDD patients
      compared to controls. We obtained similar results when the patient and control
      groups were re-studied 1 week later, and when men and current smokers were
      excluded. Basal plasma DHEA-S levels, and cortisol and ACTH response to a low
      dose dexamethasone suppression test were similar in all three groups.
      CONCLUSIONS: Lower early morning plasma cortisol levels and a high ACTH/cortisol
      ratio in subjects with PTSD and co-morbid MDD may not be due to enhanced
      peripheral sensitivity to glucocorticoids. A central abnormality in
      glucocorticoid regulation could explain HPA axis dysfunction in this subgroup.

PMID- 19766404
TI  - Function and modulation of delta-containing GABA(A) receptors.
AB  - alphabetadelta-Containing GABA(A) receptors are (1) localized to extra- and
      perisynaptic membranes, (2) exhibit a high sensitivity to GABA, (3) show little
      desensitization, and (4) are believed to be one of the primary mediators of tonic
      inhibition in the central nervous system. This type of signaling appears to play
      a key role in controlling cell excitability. This review article briefly
      summarizes recent knowledge on tonic GABA-mediated inhibition. We will also
      consider the mechanism of action of many clinically important drugs such as
      anxiolytics, anticonvulsants, and sedative/hypnotics and their effects on delta
      containing GABA receptor activation. We will conclude that alphabetadelta
      containing GABA(A) receptors exhibit a relatively low efficacy that can be
      potentiated by endogenous modulators and anxiolytic agents. This scenario enables
      these particular GABA receptor combinations, upon neurosteroid exposure for
      example, to impart a profound effect on excitability in the central nervous
      system.

PMID- 19766405
TI  - The role of the alpha 2A-adrenoceptor in mouse stress-coping behaviour.
AB  - Acute stress is known to impair memory functions in both men and laboratory
      rodents. In human the alpha 2A-adrenoceptor system is known to play a critical
      role in regulating acute neuropsychological stress responses and, ultimately,
      stress-coping behaviour. In search for neurobiological and central nervous
      mechanisms behind these behaviours we investigated if the alpha 2A-adrenoceptor
      is involved in these mechanisms in mice. Phenotypical differences between the A/J
      and C57BL/6J (B6) mouse inbred strains were evaluated in previous studies. These
      data showed significant strain differences in various motivational systems
      (anxiety, exploration, locomotion, memory etc.). From the literature it is known
      that chromosome 19 contains the gene for the adrenergic alpha 2A receptor that is
      thought to be involved in emotional behaviours, among others anxiety-related
      avoidance behaviour and arousal. We investigated if this pathway could possibly
      be involved in avoidance/arousal susceptibility by applying an agonist
      (dexmedetomidine) and an antagonist (atipamezole) of the alpha 2A-adrenoceptor to
      male mice from a consomic strain (C57BL/6J-Chr 19(A)/NaJ, abbreviated to
      CSS19=anxious), and the corresponding donor (A/J=anxious) and host (B6=non
      anxious) strains. The mice were tested in the modified hole board (mHB) test
      which allows for the assessment of a variety of behavioural patterns by use of
      only one test. In addition, a forced swimming test (FST) was conducted to test
      for stress-coping behaviour. Results of the behavioural testing in the mHB-test
      showed significant strains differences and strain-specific treatment effects for
      parameters describing anxiety-related endophenotypes. The FST revealed effects of
      dexmedetomidine and atipamezole on stress-coping behaviour. In conclusion, the
      involvement of the alpha 2A-adrenoceptor, located on mouse chromosome 19, on
      anxiety-related behaviour remains unclear and will possibly not play a main role
      in the development of anxiety-related behaviour in mice. However, we could show
      involvement of this receptor in stress-coping behaviour in mice.

PMID- 19766406
TI  - Does female ejaculation serve an antimicrobial purpose?
AB  - Women have glandular tissue below the bladder and surrounding the urethra that
      appears to be homologous to the male prostate. This tissue (also called "female
      prostate" or Skene's glands) appears to the source of a viscous, white secretion,
      which exits from the urethra upon sexual stimulation in some women. Analysis of
      this secretion (also known as "female ejaculate"), and comparison with pre-coital
      urine from the same women, revealed that its composition was unlike urine and
      often contained components also found in male seminal fluid (minus the sperm).
      The female ejaculate had lower levels of creatinine, but had elevated levels of
      prostate specific antigen, prostatic acidic phosphatase, prostate specific acid
      phosphatase, and glucose. The functional importance of female ejaculate has yet
      to be fully elucidated. It is possible that retention of a prostatic tissue
      homolog and its glandular secretion in women is merely a vestige of development
      and differentiation from an embryonic, gender-neutral body plan. We hypothesize
      that female ejaculation has a unique function in producing a secretion into the
      urethra that provides protection from urinary tract infections (UTIs). We further
      predict that female ejaculate contains antimicrobial compounds including elements
      such as zinc. We also hypothesize that retention of prostatic tissue and an
      ability to ejaculate its glandular secretion were maintained in women because
      these traits provided an evolutionary advantage. Specifically: (1) women who
      could ejaculate antimicrobial secretions into the urethra were less likely to
      suffer UTIs (particularly coitus-induced UTIs), (2) women without UTIs were more
      likely to be receptive to coitus at a greater frequency, (3) women engaging in
      frequent coitus were more likely to become pregnant, and (4) women who became
      pregnant often were more likely to successfully reproduce the species.

PMID- 19766407
TI  - Why are women so intelligent? The effect of maternal IQ on childhood mortality
      may be a relevant evolutionary factor.
AB  - Humans are an unusual species because they exhibit an economic division of
      labour. Most theories concerning the evolution of specifically human intelligence
      have focused either on economic problems or sexual selection mechanisms, both of
      which apply more to men than women. Yet while there is evidence for men having a
      slightly higher average IQ, the sexual dimorphism of intelligence is not obvious
      (except at unusually high and low levels). However, a more female-specific
      selection mechanism concerns the distinctive maternal role in child care during
      the offspring's early years. It has been reported that increasing maternal
      intelligence is associated with reducing child mortality. This would lead to a
      greater level of reproductive success for intelligent women, and since
      intelligence is substantially heritable, this is a plausible mechanism by which
      natural selection might tend to increase female intelligence in humans. Any
      effect of maternal intelligence on improving child survival would likely be
      amplified by assortative mating for IQ by which people tend to marry others of
      similar intelligence - combining female maternal and male economic or sexual
      selection factors. Furthermore, since general intelligence seems to have the
      functional attribute of general purpose problem-solving and more rapid learning,
      the advantages of maternal IQ are likely to be greater as the environment for
      child-rearing is more different from the African hunter-gatherer society and
      savannah environment in which ancestral humans probably evolved. However, the
      effect of maternal IQ on child mortality would probably only be of major
      evolutionary significance in environments where childhood mortality rates were
      high. The modern situation is that population growth is determined mostly by
      birth rates; so in modern conditions, maternal intelligence may no longer have a
      significant effect on reproductive success; the effect of female IQ on
      reproductive success is often negative. Nonetheless, in the past it is plausible
      that the link between maternal IQ and child survival constituted a strong
      selection pressure acting specifically on women.

PMID- 19766408
TI  - Synchronous squamous cell carcinoma of the kidney, squamous cell carcinoma of the
      ureter, and sarcomatoid carcinoma of the urinary bladder: a case report.
AB  - The author presents a unique case of a synchronous triple carcinoma of kidney,
      ureter, and urinary bladder. A 73-year-old man was admitted to our hospital
      because of hematuria and lumbago. Endoscopy and imaging modalities revealed a
      bladder tumor, a left ureter tumor, and a left kidney tumor. No other tumors were
      found in the body by imaging modalities. Cystectomy and left nephroureterectomy
      were performed. The bladder tumor was a large polypoid tumor consisting of
      pleomorphic sarcomatoid carcinoma (80%) and high-grade papillary urothelial
      carcinoma (20%), both invading the deep muscle layer. There were gradual merges
      between the two. The sarcomatous component was composed of malignant spindle,
      polygonal, and giant cells. Lymphovascular permeation was pronounced.
      Immunohistochemically, the sarcomatous element was positive for vimentin and
      various types of cytokeratins (CK), while the urothelial carcinoma element was
      positive for various types of CK and negative for vimentin. The ureter tumor was
      small and obstructed the ureter lumen. It was a pure squamous cell carcinoma
      without a urothelial component. The ureter tumor invaded the adventitia. A mild
      degree of lymphovascular invasion was recognized. Immunohistochemically, the
      tumor cells were positive for various types of CK but negative for vimentin. In
      the kidney, almost the entire kidney parenchyma was replaced by a tumor. The
      renal pelvis was broadly erosive but was free of apparent tumors. Histologically,
      the renal tumor was a pure squamous cell carcinoma without a urothelial
      component. Broad necrosis was present, and lymphovascular permeation was
      pronounced. The renal pelvis and calices were devoid of apparent tumor cells, but
      renal squamous cell carcinoma was present just beneath the pelvis and calices.
      Immunohistochemically, the kidney tumor was positive for various types of CK and
      negative for vimentin.

PMID- 19766409
TI  - Cold intolerance in surgically treated neuroma patients: a prospective follow-up
      study.
AB  - PURPOSE: Cold intolerance may impose great changes on patients' lifestyle, work,
      and leisure activities, and it is often severely disabling. This study aims to
      investigate the prevalence and severity of cold intolerance in patients with
      injury-related neuromas of the upper extremity and improvement of symptoms after
      surgical treatment. Furthermore, we try to find predictors for cold intolerance
      and correlations with other symptoms. METHODS: Between January 2006 and February
      2009, 34 consecutive patients with surgically treated neuroma-specific
      neuropathic pain of the upper extremities were sent a questionnaire composed of
      general questions concerning epidemiologic variables and several specific
      validated questionnaires, including the Visual Analog Scale for pain. To estimate
      the prevalence of cold intolerance objectively in neuroma patients, we used the
      validated CISS (Cold Intolerance Symptom Severity) questionnaire with a
      prespecified cutoff point. RESULTS: The CISS questionnaire was filled out by 33
      patients before and 30 after surgery for neuroma-specific neuropathic pain, with
      a mean follow-up time of 24 months. We found a prevalence of cold intolerance of
      91% before surgery, with a mean CISS score above the cutoff point for abnormal
      cold intolerance. After surgery, the prevalence of cold intolerance and the mean
      CISS score were not significantly different, whereas the mean Visual Analog Scale
      score decreased significantly (p < .01). CISS scores were lower in patients with
      neuromas associated with sharp injury of the peripheral nerve (p = .02). A higher
      VAS score correlated significantly with a higher CISS score (p = .01).
      CONCLUSIONS: Cold intolerance is a difficult and persistent problem that has a
      high prevalence in patients with a painful injury-related neuroma. There seems to
      be a relationship between severity of cold intolerance as measured by CISS, pain
      as measured by the Visual Analog Scale, and type of injury. Cold intolerance may
      not disappear with time or surgical treatment. TYPE OF STUDY/LEVEL OF EVIDENCE:
      Therapeutic IV.

PMID- 19766410
TI  - Lunate-lunate facet ratio and variance to predict articular gap after distal
      radius fracture.
AB  - PURPOSE: Intra-articular gap is a well-defined prognosticator of outcome after
      distal radius fracture. However, it is often difficult to assess on plain
      radiographs, particularly in the sagittal plane, as visualized on the lateral
      view. The purposes of this study were to establish normal values for the lunate
      lunate facet ratio (LLFR) and to evaluate whether the LLFR and lunate-lunate
      facet variance (LLFV) are reliable plain film measures of sagittal articular gap
      in distal radius fractures compared with sagittal reconstructions of computed
      tomography (CT) scans. METHODS: We studied 35 uninjured, skeletally mature wrist
      radiographs to establish the normal LLFR value. The LLFR was defined as the ratio
      of the maximum width of the lunate (A) to the width of a line spanning the
      maximum distance from dorsal to volar across the articular surface of the lunate
      facet, defined by the end point of the radiographically thickened line
      representing the subchondral bone (B). The LLFV was determined as measurement B
      minus measurement A. Interobserver and intraobserver reliability for 2 observers
      were examined by the intraclass correlation coefficient (ICC) for measurements of
      the uninjured wrists and for the same measurements of 20 intra-articular distal
      radius fractures. For 12 of the subjects with fractures, the LLFR and LLFV were
      correlated with the intra-articular gap as measured on CT scan using simple
      linear regression. RESULTS: The mean value of the LLFR in the normal subjects was
      1.00 +/- 0.04 for observer 1 and 1.00 +/- 0.02 for observer 2. There was
      significant intraobserver reliability for both uninjured (ICC = 0.83, p < .001)
      and fractured wrists (ICC = 0.87, p < .001), as well as significant interobserver
      reliability for uninjured (ICC = 0.69, p < .001) and fractured wrists (ICC =
      0.64, p = .015). The LLFR was significantly associated with articular gap on
      sagittal CT reconstructions (R(2) = -0.81, p < .01). The LLFV correlated highly
      with articular gap on sagittal CT reconstructions (R(2) = 0.83, p < .01).
      CONCLUSIONS: The LLFR, measured on the lateral radiograph of the wrist, exhibits
      high intraobserver and interobserver reliability, with a normal value of 1.0.
      Both the LLFR and the LLFV are significantly related to articular gap on sagittal
      CT reconstruction images. The LLFR decreases with increasing intra-articular gap
      formation. The LLFV allows a direct estimation of articular gap size. TYPE OF
      STUDY/LEVEL OF EVIDENCE: Diagnostic III.

PMID- 19766411
TI  - Bovine immunodeficiency virus produces a transient viraemic phase soon after
      infection in Bos javanicus.
AB  - Infection of Bali cattle (Bos javanicus) in Indonesia with a non-pathogenic
      bovine lentivirus similar to Bovine immunodeficiency virus (BIV) is suspected but
      efforts to detect the virus have been unsuccessful. To define the kinetics of BIV
      infection in Bali cattle, 13 were infected with the R-29 strain of BIV and
      monitored for 60 days. No clinical effects were detected. Proviral DNA was
      detected in peripheral blood mononuclear cells from 4 to 60 days with peak titres
      20 days post-infection (dpi). There was a transient viraemia from 4 to 14 dpi
      with a maximum titre of 1x10(4)genome copies/ml plasma. An antibody response to
      the transmembrane (TM) glycoprotein commenced 12 dpi but an antibody response to
      the capsid (CA) protein was detected in one animal only and not until 34 dpi. The
      results indicated that detection of BIV in infected Bali cattle would have a
      greater chance of success soon after infection and prior to the onset of a CA
      antibody response.

PMID- 19766412
TI  - The knowns and unknowns of human milk banking.
AB  - The PREM Bank has been providing pasteurised donor human milk (PDHM) to very
      preterm for the past 3 years. It is the first human milk bank (HMB) to operate in
      Australia in over 20 years. Our community has rapidly embraced the concept of
      human milk banking, with both donations and demand for PDHM exceeding
      expectations. Providing PDHM in 'exceptional circumstances' where a mothers' own
      milk is unavailable is supported by the WHO and UNICEF. We submit that neonatal
      intensive care is an exceptional circumstance. Although evidence supporting PDHM
      use from randomised control trial (RCT) is limited, the latest systematic reviews
      suggest a lower risk of necrotising enterocolitis with PDHM as opposed to
      artificial formula. Study design and ethical issues may limit future evidence
      from RCT. We therefore support the ongoing use of PDHM in neonatal care, where
      provided by an appropriately managed HMB. Internationally many HMBs operate
      unregulated, and this is also the case in Australia. To ensure safety the PREM
      Bank has committed to meet the appropriate standards recommended in the Code of
      Good Manufacturing Practices (Blood and Tissues) in Australia and models risk
      management during processing on Codex HACCP (Hazard Analysis Critical Control
      Point) requirements. There is scope to continually re-evaluate the screening of
      donors and quality standards recommended during HMB. This will be most effective
      if strong networks of HMBs are developed with regional reference laboratories to
      encourage compliance with safety guidelines. HMB networks will facilitate
      collection of evidence for refining HMB practice and improving outcomes for
      preterm and sick infants.

PMID- 19766413
TI  - Evaluation of management variables to advance conception and calving date of red
      deer (Cervus elaphus) in New Zealand venison production systems.
AB  - The ability to shift the supply of New Zealand chilled venison from farmed
      yearling red deer stags to obtain premium prices in seasonal European markets
      necessitates early calving of hinds combined with high growth rates of their
      calves. Two studies over a three-year period evaluated three management variables
      that offer potential to advance calving date. Under the conditions of the studies
      there was no consistent evidence that the management practices of early stag
      introduction, early weaning and enhanced hind nutrition prior to conception
      (lactation) and pre-calving (third trimester of pregnancy) advanced conception
      date and calving date in red deer hinds. However, the nutrition effect was
      diminished by the difficultly in achieving the dietary contrast necessary for the
      targeted 5kg differentiation in hind live weight at strategic times of the year.
      Across all hinds there was a significant pre-mating (mid-March) live weight
      effect on conception day in the one year in which a 5kg difference between
      nutritional regimens was achieved, but the driver was live weight and not
      nutrition. There were significant effects of nutrition on calf growth, with the
      growth rates of calves weaned in mid-March significantly higher when their dams
      grazed a high plane of nutrition pre-conception. There were significant and
      consistent inverse relationships between conception day and calving date that
      implied variation around gestation length, with early- and late-conceiving hinds
      exhibiting longer and shorter gestation lengths, respectively. Across all
      treatments, calving date was predicted to advance by approximately 5 days for
      every 10-day advance in conception date. However, there was a significant carry
      over effect of nutrition pre-conception on calving date, with hinds on a high
      plane of nutrition pre-conception exhibiting shorter (2-4 days) gestation
      lengths. There were also indications that hinds may manipulate gestation length
      in response to live weight gain pre-calving. These findings suggest that fetal
      growth trajectory may be the principle driver of gestation length and calving
      date. Although there were no direct effects of hind nutrition pre-mating on
      conception dates, nutrition remains an important component of the management of
      hinds and their calves in venison production systems. The outcomes of the 3-year
      program suggest that there are limited opportunities to manipulate calving date
      through manipulation of management variables.

PMID- 19766414
TI  - Bioidentical hormones for maturing women.
AB  - Despite medical progress, climacteric symptoms still exist. With the coming of
      age of the baby boomers, more and more women will be experiencing these symptoms
      which may be adversely affecting their lives. Mistrust of the medical community
      and prescription drugs has led many to search for that perfect product which will
      ameliorate their symptoms, with less or no risk. They are turning to compounded
      bioidentical hormones. However, the term is somewhat nebulous and ill defined. In
      this review, the term will be explained and evidence regarding efficacy and
      safety discussed.

PMID- 19766415
TI  - The analytical profile of some 4-methylthioamphetamine (4-MTA) homologues.
AB  - The 4-methylthioamphetamine (4-MTA) is a sulphur-containing amphetamine-type
      stimulant (ATS), which appeared on the illicit market in Europe at the end of
      90s. For the purpose of this study, several N-alkyl homologues of 4-MTA,
      including 4-methylthiomethamphetamine (4-MTMA), 4-methylthioethylamphetamine (4
      MTEA), 4-methylthiodimethamphetamine (4-MTDMA), 4-methylthiopropylamphetamine (4
      MTPA) and 4-methylthiobutylamphetamine (4-MTBA) were synthesized. The homologues
      were characterized by means of gas chromatography/mass spectrometry (GC-MS),
      infrared (IR) spectroscopy and the magnetic resonance spectroscopy ((1)H and
      (13)C NMR). The gas chromatography and mass spectrometry properties of their
      acetyl, trifluoroacyl (TFA), pentafluoropropionyl (PFP) and heptafluorobutyryl
      (HFB) derivatives were also investigated and discussed.

PMID- 19766416
TI  - [Overweight prevalence in preadolescents, adolescents and young adults with
      intellectual disability schooled in specialized institutions in Southeast of
      France: An exploratory study].
AB  - BACKGROUND: Prevalence of obesity is growing worldwide, especially in the
      population of adolescents with intellectual disability. Nevertheless, no study
      has focused on this problem in France. The objective of this work was thus to
      study body weight in French preadolescents, adolescents and young adults with
      intellectual disability schooled in specialized institutions. METHODS: Four
      hundred and twenty French participants with intellectual disability, aged 11 to
      21, were included in the study. An epidemiological questionnaire was built and
      distributed to 14 specialized institutions where the participants were schooled.
      The following participants' characteristics were collected: age, sex, level of
      disability, psychopathology, genetic disorder and medication. International
      Obesity Task Force (IOTF) cut-off for adolescents and World Health Organisation
      cut-off for adults based on body mass index were used to define preobesity and
      obesity. Data were analysed with t-tests, analysis of variance and Chi(2) tests.
      RESULTS: 30.2% of participants were overweight, including 9.5% exhibiting
      obesity. Results showed that: girls were significantly more concerned by
      preobesity than boys; individuals with Down's syndrome were significantly more
      obese than those without genetic disorder; individuals taking psychotropic
      medications were significantly more obese than those who did not; no difference
      in prevalence could be identified regarding the level of intellectual disability
      and the presence or not of pervasive developmental disorders. CONCLUSION: The
      prevalences observed in this study are clearly higher than those observed in the
      general population. This creates a supplementary handicap for the social
      inclusion of this population. Specialized institutions should become aware of the
      recent development of this secondary illness.

PMID- 19766417
TI  - [Incidental ultrasound finding of a 3 cm liver nodule in a 45-year-old woman
      taking hormonal substitution after hysterectomy performed for cervix carcinoma].
AB  - Incidental liver nodules are more and more frequently encountered because of
      increasing sensitivity of recent imaging techniques. The identification of
      biliary cyst or hemangioma is usually easy. In other cases, the etiological
      diagnosis relies on careful radiological analysis of the pattern of the arterial
      phase enhancement following contrast medium injection. When there is no early
      arterial enhancement, a liver biopsy is usually indicated to establish the
      diagnosis. A strong arterial contrast enhancement pattern is indicative of
      hepatocellular tumor, benign or malignant. In this situation, it is crucial to
      establish if there is underlying liver fibrosis. In case of cirrhosis, the
      diagnosis of hepatocellular carcinoma is the most probable. If the non tumorous
      liver is normal, focal nodular hyperplasia and hepatocellular adenoma should be
      differentiated. The distinction between these two tumors is important because
      only hepatic adenoma carries a significant risk of complications (bleeding or
      hepatocellular carcinoma) leading to surgical resection of lesions that do not
      regress after steroid withdrawal. Contrast enhanced MRI and contrast ultrasound
      are most useful tools for the diagnosis of nodular regenerative hyperplasia but
      liver biopsy can be necessary in atypical forms. In recent years, the
      understanding of molecular mechanisms associated with adenoma occurrence allowed
      for the proposal of a new classification already of practical interest in the
      management of patients.

PMID- 19766418
TI  - Genetic alterations in precancerous pancreatic lesions and their clinical
      implications.
AB  - Pancreatic adenocarcinoma, with an incidence/death ratio of 0.99, has the worst
      prognosis of all cancers. Risk factors associated with the sporadic form of
      pancreatic adenocarcinoma are unknown and less than 10% of patients receive
      curative treatment (surgery associated with radiation therapy or chemotherapy)
      with a low 5-year survival rate (10 to 20%). In more than 90% of patients, the
      tumor discovered at diagnosis is not resectable or has already metastasized.
      Thus, a better understanding of the etiology of pancreatic cancer is essential to
      identify new prognostic markers and new therapeutic targets. There is a wealth of
      data on the identification of genetic alterations associated with pancreatic
      cancer and their role in its development. This review will focus on the current
      knowledge of genetic alterations associated with two pancreatic lesions that can
      potentially evolve into pancreatic adenocarcinoma, Pancreatic Intraepithelial
      Neoplasia (PanIN) and Intraductal Papillary Mucinous Neoplasm (IPMN). These two
      lesions share a large panel of typical genetic alterations which are close to
      those found in pancreatic adenocarcinoma. A better understanding of these
      alterations may lead to therapeutic targets that could help prevent the
      progression of PanIN and IPMN to cancer.

PMID- 19766419
TI  - The routine use of CT enterography with positive enteric contrast in patients
      with non-traumatic acute abdominal pain.

PMID- 19766420
TI  - Update on digital radiography.

PMID- 19766421
TI  - Feasibility of post-gadolinium three-dimensional gradient-echo sequence to
      evaluate the pulmonary arterial vasculature.
AB  - PURPOSE: To determine the feasibility of post-gadolinium three-dimensional
      gradient-echo (3D-GE) sequence for the evaluation of the pulmonary arterial
      vasculature in patients with suspected pulmonary embolism (PE) and in patients
      with a variety of other disease processes. MATERIALS AND METHODS: Twenty-six
      consecutive patients (18 females, 8 males; mean age+/-S.D., 46.6+/-21.1 years)
      who underwent chest magnetic resonance imaging (MRI) including post-gadolinium 3D
      GE sequence for the evaluation of PE (Group A, n=13) and a variety of other
      disease processes (Group B, n=13) were included in the study. Post-gadolinium 3D
      GE MR sequences were retrospectively, independently and blindly evaluated by two
      reviewers for the image quality of pulmonary arterial vasculature, and findings
      of PE and other disease processes. Clinical and imaging follow-up data for all
      patients were obtained. Interobserver agreement was calculated by kappa
      statistics. RESULTS: All central and lobar pulmonary arteries, 71.4-89.6% of
      segmental arteries and 46.7-52.7% of subsegmental arterial units in both groups
      were visualized with sufficient diagnostic image quality on post-gadolinium 3D-GE
      sequences. PE involving lobar and segmental arteries was diagnosed in two
      patients in each group. Other disease processes including pneumonia, lung
      nodules, superior vena cava stenosis, lung metastases, chronic lymphocytic
      leukemia and aortic aneurysm were detected in 10 of 26 patients. There was good
      to excellent interobserver agreement (0.73 to 1.00) for all findings. CONCLUSION:
      Post-gadolinium 3D-GE sequence may be an alternative technique for the
      visualization of central, lobar and segmental arteries, and may diagnose PE and
      other pathologies involving the chest in different patient populations.

PMID- 19766422
TI  - 3D sensitivity encoded ellipsoidal MR spectroscopic imaging of gliomas at 3T.
AB  - PURPOSE: The goal of this study was to implement time efficient data acquisition
      and reconstruction methods for 3D magnetic resonance spectroscopic imaging (MRSI)
      of gliomas at a field strength of 3T using parallel imaging techniques. METHODS:
      The point spread functions, signal to noise ratio (SNR), spatial resolution,
      metabolite intensity distributions and Cho:NAA ratio of 3D ellipsoidal, 3D
      sensitivity encoding (SENSE) and 3D combined ellipsoidal and SENSE (e-SENSE) k
      space sampling schemes were compared with conventional k-space data acquisition
      methods. RESULTS: The 3D SENSE and e-SENSE methods resulted in similar spectral
      patterns as the conventional MRSI methods. The Cho:NAA ratios were highly
      correlated (P<.05 for SENSE and P<.001 for e-SENSE) with the ellipsoidal method
      and all methods exhibited significantly different spectral patterns in tumor
      regions compared to normal appearing white matter. The geometry factors ranged
      between 1.2 and 1.3 for both the SENSE and e-SENSE spectra. When corrected for
      these factors and for differences in data acquisition times, the empirical SNRs
      were similar to values expected based upon theoretical grounds. The effective
      spatial resolution of the SENSE spectra was estimated to be same as the
      corresponding fully sampled k-space data, while the spectra acquired with
      ellipsoidal and e-SENSE k-space samplings were estimated to have a 2.36-2.47-fold
      loss in spatial resolution due to the differences in their point spread
      functions. CONCLUSION: The 3D SENSE method retained the same spatial resolution
      as full k-space sampling but with a 4-fold reduction in scan time and an
      acquisition time of 9.28 min. The 3D e-SENSE method had a similar spatial
      resolution as the corresponding ellipsoidal sampling with a scan time of 4:36
      min. Both parallel imaging methods provided clinically interpretable spectra with
      volumetric coverage and adequate SNR for evaluating Cho, Cr and NAA.

PMID- 19766423
TI  - Simultaneous enantioseparation of a basic active pharmaceutical ingredient
      compound and its neutral intermediate using reversed phase and normal phase
      liquid chromatography with a new type of polysaccharide stationary phase.
AB  - Simultaneous enantioseparation of a basic API compound, (R)-2-Amino-N-[2-[1,2
      dihydro-1-(methylsulfonyl) spiro [3H-indole-3,4'-piperidin]-1'-yl]-2-oxo-1
      [(phenylmethyloxy) ethyl]-2-methylpropanamide monomethanesulfonate (compound-A)
      and its neutral penultimate intermediate, (R)-2-BOC-Amino-N-[2-[1,2-dihydro-1
      (methylsulfonyl) spiro [3H-indole-3,4'-piperidin]-1'-yl]-2-oxo-1
      [(phenylmethyloxy) ethyl]-2-methylpropanamide monomethanesulfonate (compound-B)
      was investigated using reversed phase (RPLC) and normal phase liquid
      chromatography (NPLC). After an initial screening, a Sepapak-4 column, a new type
      of polysaccharide chiral stationary phase (CSP), was selected for further method
      development based on hits on separation selectivity for both compounds under RPLC
      and NPLC. After comparing the pros and cons, a method utilizing the Sepapak-4
      chiral column (150 mm x 4.6 mm, 3 microm particle size) in RPLC mode was finally
      developed. Separations were performed in gradient elution mode starting at 50% A
      (10 mM, NH(4)COOH at pH 6.5)/50% B (50/50 EtOH/MeCN) to 25% A (10 mM, NH(4)COOH
      at pH 6.5)/75% B (50/50 EtOH/MeCN). The flow rate was 1.0 mL/min; the column
      temperature was 50 degrees C; the UV wavelength was 220nm and the mass
      spectrometric detection was APCI in the positive ionization mode. The reaction
      mixture sample was directly diluted in ethanol. Baseline enantioseparation were
      achieved for both compound-A and its intermediate simultaneously with resolution
      greater than 2.0. The method was validated in terms of injection precision,
      linearity, limit of detection (LOD), limit of quantitation (LOQ), accuracy, and
      ruggedness. The specificity of the method was further evaluated by spiking a
      mixture of enantiomers of compound-A and its intermediate into a reaction matrix
      containing all of the synthetic reagents. No matrix interference was observed
      across the elution windows of compound-A and its intermediate. Additionally, the
      peak purity of each enantiomer was evaluated by mass spectra, indicating the
      specificity of the method.

PMID- 19766424
TI  - Near-infrared chemical imaging (NIR-CI) for counterfeit drug identification--a
      four-stage concept with a novel approach of data processing (Linear Image
      Signature).
AB  - A new stage concept was developed to reliably identify counterfeit tablets which
      are very similar to the genuine drug product. This concept combines single-point
      near-infrared spectroscopy (NIRS) and near-infrared chemical imaging (NIR-CI)
      with statistical variance analysis. The advantage of NIR-CI over NIRS is the
      potential to determine not only the amount, but also the spatial distribution of
      ingredients within a single tablet. Previously published NIR-CI studies used
      homogeneity as a key indicator for the identification of counterfeits. The state
      of the art approach for estimating homogeneity is to record the average and %
      standard deviation of predicted classification scores (i.e. concentrations) for a
      given component within a specimen. A disadvantage of this approach is the partial
      loss of spatial information. In view of this, we developed a new method using
      much more of the spatial information for the estimation of homogeneity. The
      method is based on (1) summation and unfolding of multidimensional predicted
      classification scores, which results in a Linear Image Signature (LIS) and (2)
      multivariate LIS data analysis (LIS-MVA). It could be demonstrated that this kind
      of NIR-CI data analysis represents an innovative approach for the identification
      of counterfeit tablets. Moreover, this procedure is applicable to determine the
      product variability, i.e. process signature of a given product thus being a
      valuable tool within the Quality by Design (QbD) approach of the ICH Q8
      guideline.

PMID- 19766425
TI  - Clinical and molecular epidemiology of methicillin-resistant Staphylococcus
      aureus carrying SCCmecIV in a university hospital in Porto Alegre, Brazil.
AB  - We evaluated clinical outcomes and molecular epidemiology of methicillin
      resistant Staphylococcus aureus carrying SCCmecIV recovered from patients who
      attended at a teaching hospital from Porto Alegre, Brazil. All Panton-Valentine
      leukocidin (PVL)-producer isolates belonged to clonal complex (CC) 30 (11
      isolates, related to Oceania Southwest Pacific clone [OSPC]), and the PVL
      negative isolates were typed as CC5 (2 isolates, related to the pediatric clone).
      Five patients had health care-associated infections (HCAIs) with hospital-onset,
      5 HCAIs with community-onset, and 3 community-acquired infections without risks.
      A high overall mortality (30.8%) was found. This study show that OSPC isolates
      are not only causing community-associated infections but are also involved in
      HCAI in our country.

PMID- 19766426
TI  - Panton-Valentine leukocidin (PVL)-positive methicillin-susceptible and resistant
      Staphylococcus aureus in Taiwan: identification of oxacillin-susceptible mecA
      positive methicillin-resistant S. aureus.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) arises when methicillin
      susceptible S. aureus (MSSA) acquires the staphylococcal cassette chromosome mec
      (SCCmec). Most pvl-positive MRSA in Taiwan belong to ST59 lineage and carry
      SCCmec V. The genetic profiles of 51 MSSA were compared with those of 80 MRSA
      from the same hospitals. Nine pvl-positive MSSA (oxacillin MIC < or = 2
      microg/mL) shared >80% similarity in pulsed field gel electrophoresis pattern
      with 17 pvl-positive SCCmec V MRSA. Further investigation found that 5 of these 9
      isolates were MRSA by cefoxitin and carried SCCmec V. All 26 pvl-positive
      isolates had very similar genetic profile (ST59, protein A clonal complex [spa
      CC] c2:441/437, and agr group I). The success of the ST59:SCCmec V MRSA may be
      due in part to its heterogeneous and borderline resistance to methicillin, which
      may be missed by testing only oxacillin, with subsequent exposure to beta-lactams
      causing the emergence of more resistant subpopulations.

PMID- 19766427
TI  - The Helicobacter pylori Mfd protein is important for antibiotic resistance and
      DNA repair.
AB  - A Helicobacter pylori mutant defective in a putative mfd gene was constructed and
      characterized. The mfd gene is required for DNA repair and is involved in DNA
      recombination processes. The mfd mutant strain displayed a greatly increased
      susceptibility to antibiotics, indicating that this gene plays a significant role
      in the antibiotic resistance of H. pylori strain J99.

PMID- 19766428
TI  - Diversity of the bla(SHV) genes.
AB  - We investigated the diversity of nucleotide sequences of 297 SHV-encoding genes,
      based on nucleotide synonymous mutations and the presence or absence of the
      nonsynonymous mutation T92A. The analysis of this diversity allowed us to develop
      and propose a classification to differentiate the nucleotide sequence variants of
      the bla(SHV) genes.

PMID- 19766429
TI  - Lactobacillus rhamnosus hepatic abscess associated with Mirizzi syndrome: a case
      report and review of the literature.
AB  - The clinical significance of Lactobacillus spp. isolated from clinical specimens
      has often been overlooked due to its low virulence. We report the first case of
      life-threatening bacteremic liver abscess due to Lactobacillus rhamnosus
      associated with Mirizzi syndrome in a 74-year-old Chinese man. Literature on
      sporadic reports of Lactobacillus liver abscess is reviewed.

PMID- 19766430
TI  - In vivo selection of carbapenem-resistant Klebsiella pneumoniae by OmpK36 loss
      during meropenem treatment.
AB  - We recovered a carbapenem-resistant Klebsiella pneumoniae isolate H224 under in
      vivo meropenem selection pressure. Insertional inactivation of a major porin
      gene, ompK36, by IS5 element might play a role in acquiring carbapenem resistance
      in this strain harboring plasmid-borne DHA-1 AmpC beta-lactamase.

PMID- 19766431
TI  - Diagnostic value of enzyme-linked immunosorbent assays using hypothetical
      proteins CT226 and CT795 as antigens in Chlamydia trachomatis serodiagnosis.
AB  - The CT226 and the CT795 proteins were produced as purified recombinant proteins
      and were used as antigens in enzyme-linked immunosorbent assay (ELISA) tests for
      the detection of Chlamydia trachomatis IgG antibodies. The performances of the
      developed ELISA tests were compared with our in-house microimmunofluorescence
      test and the species-specific pELISA test using a panel of 342 sera. Our results
      indicate that the performance of the CT795 ELISA test was higher than that of the
      CT226 ELISA test according to the microimmunofluorescence and to the pELISA. To
      assess whether a combination of tests could improve the serodiagnosis of C.
      trachomatis infections, we associated results obtained with these tests to that
      using the previously developed CT694 ELISA test. Combining ELISA test results did
      not improve significantly the performances of these ELISA tests. The CT795 ELISA
      test, showing the highest performance, may be used for the serodiagnosis of C.
      trachomatis infections.

PMID- 19766432
TI  - Usefulness and influence of age of a novel Rapid HpStAR stool antigen for the
      diagnosis of Helicobacter pylori infection in children.
AB  - A novel rapid monoclonal enzyme immunoassay stool antigen for Helicobacter pylori
      detection (Rapid HpStAR) was evaluated in 16 infected and 92 noninfected
      children. The overall sensitivity, specificity, and positive and negative
      predictive values were 87.5%, 97.8%, 87.5%, and 97.8%, respectively, with an
      accuracy of 96.2%. The negative predictive value was good in all age groups,
      reaching 100% in younger children.

PMID- 19766433
TI  - Comparison of nucleic acid extraction methods for the detection of Mycoplasma
      pneumoniae.
AB  - Four nucleic acid extraction procedures (2 automated and 2 manual) were compared
      for their efficiency at isolating Mycoplasma pneumoniae DNA. Oropharyngeal swabs
      from healthy volunteers were spiked with varying amounts of M. pneumoniae,
      extracted, and tested using real-time polymerase chain reaction. Our data
      indicate that both automated extraction methods consistently outperform the
      manual procedures.

PMID- 19766434
TI  - Treatment of bartholin abscesses.

PMID- 19766435
TI  - Adult colo-colonic intussusception incidentally detected by emergency bedside
      gallbladder sonography.

PMID- 19766436
TI  - Development and use of a decision aid for communication with hospitalized
      patients about cardiopulmonary resuscitation preference.
AB  - OBJECTIVE: To develop and evaluate a decision aid related to CPR decision-making
      for hospitalized patients. METHODS: The development of the decision aid was
      guided by published recommendations; physicians, nurses, and a clinical ethicist
      were involved in the process. In-patients over age 55 with serious illnesses and
      their family were involved in pre-testing and evaluation. RESULTS: Twenty-five
      patients and 11 family members participated. The majority (23/25, 92% of
      patients, 7/11, 64% of family) reported the information in the decision aid was
      'Very' or 'Extremely' helpful in decisions. More than 70% of patients and family
      considered the aid to be "acceptable." The decision aid did not appear to bias
      towards or away from preferences for CPR. Participants did not report significant
      burden with use (median score 2/10; 1=none, 10=extremely upsetting). All patients
      and 10 family members recommended the aid be available to all patients.
      CONCLUSION: The decision aid was felt to be acceptable, feasible, and useful by
      participants. Future research should evaluate the impact of the decision aid on
      outcomes including quality of decision-making. PRACTICE IMPLICATIONS: The
      decision aid can be used to assist with CPR decision-making with seriously ill
      hospitalized patients. It is available for use on the CARENET website.

PMID- 19766437
TI  - [Severe overdose in vitamin K antagonist secondary to grapefruit juice
      absorption].
AB  - Vitamin K antagonists (VKA) are very currently used. Nevertheless, they are known
      to interact with numerous drugs and foods. Grapefruit juice is known to interact
      with some drugs metabolized by the enterocytary cytochrome P450 3A4 but its
      interaction with drugs as VKA that have a good biodisponibility is not clearly
      demonstrated. We report here the case of a woman treated with VKA in whom massive
      absorption of grapefruit juice entailed an excessive VKA dosage and a severe
      haemorrhage.

PMID- 19766438
TI  - Biological activities of sulfated polysaccharides from tropical seaweeds.
AB  - Sulfated polysaccharides from 11 species of tropical marine algae (one edible
      specie of Rhodophyta, six species of Phaeophyta and four species of Chlorophyta)
      collected from Natal city coast (Northeast of Brazil) were evaluated for their
      anticoagulant, antioxidant and antiproliverative in vitro activities. In the
      activated partial thromboplastin time (APTT) test, which evaluates the intrinsic
      coagulation pathway, seven seaweeds presented anticoagulant activity. Dictyota
      cervicornis showed the highest activity, prolonging the coagulation time to
      double the baseline value in the APTT with only 0.01 mg/100 microl of plasma, 1.4
      fold lesser than Clexane, a low molecular weight heparin. In the protrombin time
      (PT) test, which evaluates the extrinsic coagulation pathway, only Caulerpa
      cupresoides showed anticoagulant activity. All species collected showed
      antioxidant activities. This screening emphasized the great antioxidant potential
      (total capacity antioxidant, power reducing and ferrous chelating) of four
      species: C. sertularioide; Dictyota cervicornis; Sargassum filipendula and
      Dictyopteris delicatula. After 72 h incubation, HeLa cell proliferation was
      inhibited (p<0.05) between 33.0 and 67.5% by S. filipendula; 31.4 and 65.7% by D.
      delicatula; 36.3 and 58.4% by Caulerpa prolifera and 40.2 and 61.0% by Dictyota
      menstrualis at 0.01-2mg/mL algal polysaccharides. The antiproliferative efficacy
      of these algal polysaccharides were positively correlated with the sulfate
      content (r=0.934). Several polysaccharides demonstrated promising antioxidant,
      antiproliferative an/or anticoagulant potential and have been selected for
      further studies on bioguided fractionation, isolation and characterization of
      pure polysaccharides from these species as well as in vivo experiments are needed
      and are already in progress.

PMID- 19766439
TI  - Advanced glycation endproducts increase EPC apoptosis and decrease nitric oxide
      release via MAPK pathways.
AB  - OBJECTIVE: Previous studies have shown that advanced glycation endproducts (AGE)
      can induce endothelial progenitor cells (EPC) apoptosis, which contributes to the
      pathogenesis of diabetes mellitus. Nitric oxide (NO) signaling is closely
      associated with apoptosis. We therefore investigated the effects of AGE on human
      EPC apoptosis, NO release and related signal transduction pathways. METHODS: EPC
      isolated from healthy human subjects were cultured with various concentrations of
      AGE (0, 2, 20 and 200mg/L) for 0, 24, 48 and 72 h in the presence or absence of
      various MAPK (ERK/P38/JNK) inhibitors, respectively. EPC apoptosis (detected by
      flow cytometric analyses) and NO concentration in culture supernatant were
      determined. The mRNA levels of eNOS, COX-2, Bcl-2 and Bax were assessed by RT-PCR
      and the protein expressions of NF-kappaB and Caspase-3 assessed by Western blot.
      RESULTS: Increased EPC apoptosis and reduced NO release were induced by 200mg/L
      AGE, accompanied by a downregulation of eNOS and Bcl-2 expressions as well as an
      elevation in COX-2, Bax, NF-kappaB and Caspase-3 expressions in a time-dependent
      manner (all P<0.05). These changes were significantly attenuated by pretreatment
      with various MAPK (ERK/P38/JNK) inhibitors (P<0.05). CONCLUSIONS: AGE can promote
      EPC apoptosis and decrease NO release via MAPK pathways.

PMID- 19766440
TI  - [Electronic health records and biomedical research].
AB  - The rapid progress in Web technology has led to the multiplication of health and
      research records for any given patient. Initiatives such as the personal medical
      record or the communicating cancer communicable records have recently been
      introduced. However, their primary aim is not for biomedical research. Several
      international groups of researchers are analyzing the appropriate role of the
      electronic health record as a support to biomedical research. The need to
      complete several distinct records for a given patient is a limiting factor, in
      view of the lack of medical and paramedical resources and the rising quality
      demands for both medical care and biomedical research. The impediments to
      "secondary reuse" of clinical data stored in electronic health records for
      biomedical research purposes are statutory, organizational, and technical. The
      international Integrating the Healthcare Enterprise (IHE) initiative has proposed
      a promising approach that uses an integration profile known as a Retrieve Form
      for Data Capture (RFD). A joint project by the North American Association of
      Cancer Registries and the Centers for Disease Control has made possible the
      automated transmission of pathology reports to the registries and thus limited
      the need for registry technicians to come copy these forms at the hospital.

PMID- 19766441
TI  - [Changing the teaching of neurosurgery with information technology].
AB  - A digital campus is a distance learning site that uses the potential of
      information and communication technologies to disseminate and improve educational
      services. This website, with open and free access, is built from free software
      with Web 2.0 technology. It is hosted at the University of Limoges. It functions
      as a digital library, containing scanned books, slide shows, more than 200 hours
      of recorded courses and round tables accessible by streaming video. The site is
      indexed according to the users' needs, by level of knowledge, specialty,
      keywords, and supplementary MeSH terms. The campus is organized as the College of
      Neurosurgery (http://college.neurochirurgie.fr). The durability of this type of
      training (in existence for 9 years now) is made possible by a powerful and
      committed consortium: the French Society of Neurosurgery, which has created high
      quality intellectual and scientific resources, the University of Limoges, the
      Dupuytren University Hospital Center in Limoges, the region of Limousin, and the
      French-language Virtual Medical University, which have provided logistic and
      financial support. To target appropriate levels at various users, we
      distinguished four groups: medical students, neurosurgery students, neurosurgeons
      (continuing medical education), and students in allied health fields. All areas
      of neurosurgery are concerned. All the courses, including tests for self
      evaluation and scientific meetings (organized with information and communication
      technologies) are digitally recorded for the site. The principles that make it
      possible for a medical discipline to organize around an online project are: a
      pedagogical conception of projects built in the form of models reusable by other
      health specialties; a stronghold within professional societies of the relevant
      specialties able to create high-quality intellectual and scientific resources; an
      organization by educational levels that can be extended transversally to other
      health disciplines; and free access to the digital campus, the durability of
      which depends on the dissemination and dynamism of its consortium.

PMID- 19766442
TI  - Standardization of thresholding for binary conversion of vocal tract modeling in
      computed tomography.
AB  - Postoperative head and neck cancer patients suffer from speech disorders, which
      are the result of changes in their vocal tracts. Making a solid vocal tract model
      and measuring its transmission characteristics will provide one of the most
      useful tools to resolve the problem. In binary conversion of X-ray computed
      tomographic (CT) images for vocal tract reconstruction, nonobjective methods have
      been used by many researchers. We hypothesized that a standardized vocal tract
      model could be reconstructed by adopting the Hounsfield number of fat tissue as a
      criterion for thresholding of binary conversion, because its Hounsfield number is
      the nearest to air in the human body. The purpose of this study was to establish
      a new standardized method for binary conversion in reconstructing three
      dimensional (3-D) vocal tract models. CT images for postoperative diagnosis were
      secondarily obtained from a CT scanner. Each patient's minimum settings of
      Hounsfield number for the buccal fat-pad regions were measured. Thresholds were
      set every 50 Hounsfield units (HU) from the bottom line of the buccal fat-pad
      region to -1024 HU, the images were converted into binary values, and were
      evaluated according to the three-grade system based on anatomically defined
      criteria. The optimal threshold between tissue and air was determined by
      nonlinear multiple regression analyses. Each patient's minimum settings of the
      buccal fat-pad regions were obtained. The optimal threshold was determined to be 
      165 HU from each patient's minimum settings of the Hounsfield number for the
      buccal fat-pad regions. To conclude, a method of 3-D standardized vocal tract
      modeling was established.

PMID- 19766443
TI  - Dysphonia severity degree and phonation onset latency in laryngeal adductor
      dystonia.
AB  - Although the latency between the initiation of thyroarytenoid electrical activity
      and the onset of phonation generally is increased in patients with adductor
      laryngeal dystonia, there is disagreement about whether there is overlap of
      latency values in these patients and normal subjects. The goal of this article
      was to compare the severity of dysphonia with the latency between
      electrophysiological activation of the thyroarytenoid muscle (TA) and the onset
      of phonation in patients with adductor laryngeal dystonia and compare the values
      with normal controls. Twenty-one patients with adductor dystonia and 15 control
      patients underwent laryngeal electromyographic (EMG) examination of the left TA.
      We measured the latency from initiation spike of the electric activity of the TA
      muscle to the onset of phonation. Three speech-pathologists/voice specialists
      arrived at a consensus to rate the perceptual evaluation of voice quality for the
      study group. The average latency measured for patients with mild dysphonia was
      332 milliseconds, for moderate dysphonia was 426 milliseconds, and for the severe
      dysphonia was 792 milliseconds. We used the Spearman's correlation test to
      compare the latency time values and the dysphonia's degree of severity (P<0.05).
      Latency was significantly and directly related to the degree of severity of
      dysphonia.

PMID- 19766444
TI  - Phonetograms, aerodynamic measurements, self-evaluations, and auditory perceptual
      ratings of male-to-female transsexual voice.
AB  - OBJECTIVES: This exploratory study reports instrumental and subjective data for
      25 male-to-female transsexual (M-F TS) individuals using their attempted female
      voice. The aim was to examine the usefulness of phonetograms and aerodynamic
      measures for voice assessment of this client group. STUDY DESIGN: Descriptive and
      correlational. METHODS: Phonetogram speech-range profiles (SRPs) were recorded
      for the M-F TS participants' attempted female voice. Transglottal air pressure
      and airflow were estimated from oral recordings. All recordings were made in
      typical- and loud-voice conditions. Relationships among acoustical and
      aerodynamic measurements, background data, self-evaluations, and auditory
      perceptual ratings were examined. M-F TS data were compared with male and female
      normative data. RESULTS: Agreement between naive and voice-expert listeners as
      well as intra- and interlistener reliability was good. Fundamental frequency
      (F(0)) accounted for 41-49% of variation in gender ratings for the group, but
      individual exceptions were found. Background data did not account for female
      voice success. Perceptual ratings of strain and breathiness were low. No data
      indicated hyperfunctional vocal behavior. The aerodynamic data agreed with
      normative male high-pitch data. The speech sound pressure level (SPL) was higher
      than the female norms. Phonetogram speech-range data fell between male and female
      data. CONCLUSIONS: The importance of speaking fundamental frequency (SFF) in
      perception of gender was confirmed. Instrumental and subjective data suggested
      that the use of low speech intensities and avoidance of vocal fry could help
      contribute to a successful female voice. Phonetograms were suggested to be useful
      for visual feedback and documentation of changes in voice therapy for M-F TS
      clients.

PMID- 19766445
TI  - Optimal neurocontroller synthesis for impulse-driven systems.
AB  - This paper presents a new controller design technique for systems driven with
      impulse inputs. Necessary conditions for optimal impulse control are derived. A
      neural network structure to solve the resulting equations for optimal control is
      presented. Solution concepts are illustrated with example problems that exhibit
      increasing levels of difficulty. Two linear problems, one scalar and one vector
      and a benchmark nonlinear problem, the Van Der Pol oscillator, are used as case
      studies. Numerical results show the efficacy of the new solution process for
      impulse driven systems. Since the theoretical development and the design
      technique are free from restrictive assumptions, this technique is applicable to
      many problems in engineering and science.

PMID- 19766446
TI  - Comparison of the clinical application of the American College of Cardiology
      Foundation/American Society of Echocardiography Appropriateness Criteria for
      outpatient transthoracic echocardiography in academic and community practice
      settings.
AB  - BACKGROUND: We sought to compare the clinical application of the American College
      of Cardiology Foundation/American Society of Echocardiography Appropriateness
      Criteria (AC) for outpatient transthoracic echocardiography (TTE) in academic and
      community practice settings. METHODS: Indications for TTE ordered in both
      academic and community practice settings were determined by 2 reviewers and
      categorized according to the AC for TTE as Appropriate, Inappropriate, or Not
      Addressed. Patient characteristics, ordering physician specialty, and TTE
      findings were also recorded. RESULTS: Overall, 814 academic and 319 community
      TTEs were analyzed. Interobserver variability for indication determination was
      high and did not differ between studies ordered at the 2 practice settings.
      Compared with the academic practice, community practice TTE indications were more
      likely to be classified in the AC for TTE (88% vs 82%, P = .04), but were ordered
      for a similar frequency of Appropriate (71% vs 68%, P = not significant) and
      Inappropriate (17% vs 15%, P = not significant) indications. New important TTE
      abnormalities were more frequently found in Appropriate studies compared with
      Inappropriate studies in both academic (35% vs 16%, P < .001) and community
      practice (29% vs 15%, P = .04) settings. CONCLUSION: The clinical application of
      the AC for TTE is feasible, and the frequency of Appropriate and Inappropriate
      outpatient TTEs is similar in academic and community practice settings. However,
      limitations of the AC for TTE are identified that suggest revisions will be
      needed to fully encompass and stratify the broad clinical practice of
      echocardiography.

PMID- 19766447
TI  - Malposition of a central venous catheter in the right main pulmonary artery
      detected by transesophageal echocardiography.
AB  - The authors report a case of a malpositioned central venous catheter, the
      malposition of which was not recognized on chest x-ray or chest computed
      tomography but was correctly diagnosed on transesophageal echocardiography.

PMID- 19766448
TI  - Assessment of mitral annular velocities by speckle tracking echocardiography
      versus tissue Doppler imaging: validation, feasibility, and reproducibility.
AB  - BACKGROUND: Mitral annular velocity may be measured angle independently by
      speckle tracking echocardiography (STE), in contrast with tissue Doppler imaging
      (TDI). The purpose of the current study was to compare STE and TDI, with respect
      to 1) the accuracy of velocity measurements in a moving phantom, 2) the
      feasibility and reproducibility of measurement of mitral annular velocities in a
      clinical setting, and 3) the estimation of left ventricular filling pressures
      using mitral annular velocities. METHODS: The velocity of a moving phantom, using
      different angles of insonation, and mitral annular velocities of 80 nonselected
      patients and 50 healthy volunteers were determined using TDI and STE. A subgroup
      of 20 patients was studied during right-sided heart catheterization. RESULTS:
      When the motion direction of the phantom was parallel to the ultrasound beam,
      both TDI and STE determined velocities accurately. With increasing angle of
      insonation, TDI-derived velocity decreased, whereas STE-derived velocity remained
      unchanged. The feasibility of mitral annular velocities measured by TDI and STE
      was comparable (98% vs 95%, P = not significant). Although for both techniques
      correlations between measured mitral annular velocities at repeated examinations
      were good, the test-retest variability of mitral annular velocities by TDI was
      higher. E/Em ratio by STE correlated better to pulmonary capillary wedge pressure
      (R(2) = 0.51, P < .001) compared with E/Em ratio derived from TDI (R(2) = 0.35, P
      < .01), although the difference in correlation was not statistically significant
      because of the limited sample size. CONCLUSION: Tissue velocities can be
      accurately determined by STE in a moving phantom and are angle independent, in
      contrast with TDI measurements. Furthermore, STE is a feasible and better
      reproducible method for the assessment of mitral annular velocities in a clinical
      setting.

PMID- 19766449
TI  - Microvascular function in Takotsubo cardiomyopathy with contrast
      echocardiography: prospective evaluation and review of literature.
AB  - BACKGROUND: Takotsubo cardiomyopathy (TC) mimics ST-elevation myocardial
      infarction without substantial angiographic stenosis. Coronary microvascular
      dysfunction has been proposed as a possible mechanism in TC. The aim of this
      study was to evaluate microvascular function in TC using real-time myocardial
      contrast echocardiography (MCE). METHODS: Real-time MCE was performed within 24
      hours of coronary angiographic diagnosis of TC. Myocardial perfusion was
      evaluated through qualitative and quantitative myocardial contrast
      echocardiographic analyses comparing normal segments with segments with
      dysfunctional wall motion (WM). RESULTS: From January 2007 to January 2008, 11
      patients received diagnoses of TC. Of these patients, 9 were prospectively
      enrolled (mean age, 70.9 +/- 17.5 years; 8 women). Qualitative and quantitative
      myocardial contrast echocardiographic analyses were feasible in 87% and 81% of
      segments. Overall, concordance between qualitative MCE and WM for normal versus
      abnormal analysis was observed in 71% of segments (kappa = 0.442, SE = 0.08).
      Significantly lower myocardial blood flow velocity (beta) and lower myocardial
      blood flow (Abeta) were detected in segments with dysfunctional WM compared with
      those with normal WM (beta = 0.55 +/- 0.39 vs 0.90 +/- 0.77, P = .009; Abeta =
      5.31 +/- 3.92 vs 12.38 +/- 13.47, P = .002). In the discordant segments between
      qualitative MCE and WM, the quantitative perfusion parameters beta and Abeta were
      significantly lower in segments with dysfunctional WM compared with those with
      normal WM (beta = 0.22 +/- 0.20 vs 1.79 +/- 0.57, P = .01; Abeta = 1.90 +/- 1.1
      vs 24.29 +/- 19.9, P = .02). Recovery of WM abnormalities was detected in all
      patients during follow-up echocardiography (mean, 60.3 +/- 66.0 days). No
      contrast-related side effects were reported. During mean follow-up of 5.9 +/- 4.6
      months, there were no cardiac events, but 1 noncardiac death (from lung cancer)
      occurred. CONCLUSION: TC is associated with abnormal myocardial perfusion
      detected with qualitative and quantitative MCE, indicative of microvascular
      dysfunction.

PMID- 19766450
TI  - Health-e-Child project: mechanical dyssynchrony in children with dilated
      cardiomyopathy.
AB  - OBJECTIVE: Left ventricular mechanical dyssynchrony has been poorly studied in
      the pediatric population with dilated cardiomyopathy. We investigated the degree
      of dyssynchrony in children with dilated cardiomyopathy using tissue Doppler
      imaging and speckle tracking strain. METHODS: Twenty-five children with dilated
      cardiomyopathy were compared with healthy subjects. Left ventricular mechanical
      dyssynchrony was assessed by speckle tracking strain and tissue Doppler imaging.
      Both radial and longitudinal dyssynchrony were analyzed. Left ventricular end
      diastolic diameter was measured to assess the relation between dyssynchrony and
      ventricular function and remodeling. RESULTS: Radial and longitudinal
      dyssynchrony parameters were significantly higher in the dilated cardiomyopathy
      group and correlated with Z-score left ventricular end-diastolic diameter. A
      logarithmic correlation between left ventricular ejection fraction and left
      ventricular end-diastolic diameter parameters was found. CONCLUSION: In children
      with dilated cardiomyopathy, tissue Doppler imaging and speckle tracking strain
      allowed the detection of dyssynchrony, which correlates with the severity of left
      ventricular function.

PMID- 19766451
TI  - Radiotherapy-induced mitral stenosis: a three-dimensional perspective.
AB  - Mediastinal irradiation for cancers, mainly breast cancer and Hodgkin's disease,
      has numerous potential adverse effects, including coronary artery disease,
      pericarditis, cardiomyopathy, valvular disease, and conduction abnormalities. The
      prevalence of valvular dysfunction is relatively low, and regurgitation is more
      common. We report the case of a 58-year-old woman with severe radiation-induced
      mitral stenosis and discuss the potential additional value of three-dimensional
      transesophageal echocardiography.

PMID- 19766452
TI  - Behcet's disease as a frequently unrecognized cause of aortic regurgitation:
      suggestive and misleading echocardiography findings.
AB  - BACKGROUND: Behcet's disease (BD) is a systemic vasculitis that can be a possible
      cause of aortic regurgitation (AR). When aortic valve replacement is performed in
      patients with BD, unless preoperative immunosuppressive therapy and special
      operative techniques are used, the postoperative course is usually complicated by
      valve dehiscence, necessitating another operation. The preoperative diagnosis of
      BD is challenging because of its protean manifestations, but an early diagnosis
      is associated with a more favorable prognosis. METHODS: Between 1990 and 2008, 15
      patients with final diagnoses of BD underwent aortic valve replacement. Medical
      records and echocardiographic findings were retrospectively analyzed. RESULTS: Of
      the 15 patients, only 2 were diagnosed as having BD prior to first operation.
      Twelve underwent repeat open-heart surgery because of valve dehiscence, and 6 of
      these 12 patients eventually died. In 5 patients with available echocardiographic
      findings of native valve morphology, echocardiography demonstrated characteristic
      aneurysmal changes and redundant coronary cusp motion in 4 patients. Vegetation
      like mobile lesions and echo-free spaces mimicking abscess pockets led to
      misdiagnoses of infective endocarditis in 7 patients at least once during their
      clinical courses. Furthermore, complete atrioventricular block requiring
      permanent pacemaker insertion developed in 5 patients, especially those with echo
      free spaces in the periannular area. CONCLUSIONS: Dismal prognoses are almost
      inevitable unless etiologic diagnoses are made prior to surgery in patients with
      BD and AR. It is important to diagnose BD preoperatively, and the diagnostic
      importance of echocardiographic findings should be kept in mind when evaluating
      patients with AR.

PMID- 19766453
TI  - Factors affecting sensitivity and specificity of diagnostic testing: dobutamine
      stress echocardiography.
AB  - BACKGROUND: Clinical characteristics of patients, angiographic referral bias, and
      several technical factors may all affect the reported diagnostic accuracy of
      tests. The aim of this study was to assess their influence on the diagnostic
      accuracy of dobutamine stress echocardiography (DSE). METHODS: The medical
      literature from 1991 to 2006 was searched for diagnostic studies using DSE and
      meta-analysis was applied to the 62 studies thus retrieved, including 6881
      patients. These studies were analyzed for patient characteristics, angiographic
      referral bias, and several technical factors. RESULTS: The sensitivity of DSE was
      significantly related to the inclusion of patients with prior myocardial
      infarctions (0.834 vs 0.740, P < .01) and defining the results of DSE as already
      positive in case of resting wall motion abnormalities rather than obligatory
      myocardial ischemia (0.786 vs 0.864, P < .01). Specificity tended to be lower
      when patients with resting wall motion abnormalities were included in a study
      (0.812 vs 0.877, P < .10). The presence of referral bias adversely affected the
      specificity of DSE (0.771 vs 0.842, P < .01). CONCLUSION: This analysis suggests
      that the reported sensitivity of DSE is likely higher and the specificity lower
      than expected in routine clinical practice because of the inappropriate inclusion
      of patients with prior myocardial infarctions, the definition of positive results
      on DSE, and the negative influence of referral bias. However, in the patient
      subset that will be sent to coronary angiography, the opposite results can be
      expected.

PMID- 19766454
TI  - Quantitative assessment of strain and strain rate by velocity vector imaging
      during dobutamine stress echocardiography to predict outcome in patients with
      left bundle branch block.
AB  - BACKGROUND: Abnormal septal motion in left bundle branch block (LBBB) may
      compromise the interpretation of regional wall motion. Velocity vector imaging
      (VVI) has been proposed as an objective method to quantify regional myocardial
      deformation. The aim of this study was to determine whether VVI during dobutamine
      stress echocardiography (DSE) has prognostic value in patients with LBBB.
      METHODS: In 84 patients with (mean age, 75 +/- 9 years) undergoing DSE,
      longitudinal peak systolic strain (epsilon(sys)) and strain rate (SR(sys)) were
      measured in 16 segments using VVI. Results were expressed as average SR(sys) and
      epsilon(sys) per patient. Follow-up was obtained for the combined endpoint of
      mortality, myocardial infarction, and coronary revascularization. Contributions
      of clinical, conventional dobutamine stress echocardiographic, and epsilon(sys)
      and SR(sys) variables to outcome were assessed using Cox models. RESULTS: During
      a mean follow-up period of 18.3 +/- 13.8 months, 23 patients had endpoints. Wall
      motion score index at rest was the only independent predictor in a model
      combining clinical and conventional dobutamine stress echocardiographic
      variables. However, when epsilon(sys) and SR(sys) variables were considered,
      average SR(sys) at peak stress (hazard ratio, 2.38 per 0.2/s increment; 95%
      confidence interval, 1.53-3.88; P < .0001) became the only independent predictor
      of outcome. Using average SR(sys) at peak of -0.5/s as the cut point maximized
      the model chi(2) value for the prediction of outcomes (model chi(2) = 18.71, P =
      .002). The annualized event-free survival in patients with average SR(sys) at
      peak stress lower and higher than -0.5/s were 89.9% and 45.9%, respectively (P <
      .0001). CONCLUSION: Average SR(sys) at peak stress during DSE offers prognostic
      information incremental to wall motion analysis in patients with LBBB.

PMID- 19766455
TI  - A multilevel item response theory model was investigated for longitudinal vision
      related quality-of-life data.
AB  - OBJECTIVE: To investigate how a multilevel item response theory (IRT) model for
      longitudinal dependent data could provide average and individual quality-of-life
      outcomes of low-vision rehabilitation. STUDY DESIGN AND SETTING: In a
      nonrandomized longitudinal design, visually impaired older patients (n=296) were
      referred to multidisciplinary rehabilitation or to an optometric service. The
      five-dimensional Low Vision Quality of Life Questionnaire was administered at
      four time points. The IRT model was characterized by the graded response model
      for rating scales. Covariates were added to the model, mainly to correct for
      missing data. The invariance assumption across time points was investigated.
      RESULTS: Average and individual rehabilitation effects were estimated. For
      multidisciplinary rehabilitation, significant average deterioration was seen on
      three dimensions after 4.4 years. Many individuals in the optometric service
      group significantly improved on the "reading small print" dimension (18.5%); in
      both groups, many individuals significantly deteriorated on "visual (motor)
      skills" (22.2-30.0%). Invariance across time points could be assumed for all
      dimensions, except for "adjustment." Gender, education, visual acuity, and health
      status were significantly associated with the outcome. CONCLUSION: We present how
      a multilevel IRT model can be applied to describe longitudinal dependent vision
      related quality-of-life data, while focusing on average and individual effects.

PMID- 19766456
TI  - Aetiopathogenesis of autoimmune hepatitis.
AB  - Interface hepatitis, histological hallmark of autoimmune hepatitis (AIH), is a
      dense portal mononuclear cell infiltrate invading the parenchyma, consisting of
      CD4 and CD8 T-lymphocytes, monocytes/macrophages and plasma cells. What triggers
      AIH is unknown, but there is evidence that failure of immune homeostasis plays a
      permissive role allowing liver autoantigen-specific cells to attack hepatocytes.
      Damage is likely to be orchestrated by CD4 T-lymphocytes recognizing an
      autoantigenic liver peptide. For autoimmunity to arise, the peptide, embraced by
      an HLA class II molecule, must be presented to naive CD4 T-helper (T(H)0) cells
      by professional antigen-presenting cells. Once activated, T(H)0 cells can
      differentiate into T(H)1 cells, which are pivotal to macrophage activation,
      enhance HLA class I expression, rendering liver cells vulnerable to CD8 T-cell
      attack, and induce HLA class II expression on hepatocytes; or into T(H)2 cells
      producing IL-4, IL-10 and IL-13, cytokines favouring autoantibody production by B
      lymphocytes. Autoantigen recognition is tightly controlled by regulatory
      mechanisms, such as those exerted by CD4+CD25+ regulatory T-cells (T-regs).
      Numerical and functional T-reg impairment characterizes AIH, particularly during
      active disease. Advances in the study of autoreactive T-cells stem mostly from
      AIH type 2, where the main autoantigen, CYP2D6, is known enabling
      characterization of antigen-specific immune responses. Monocyte involvement in
      the autoimmune liver attack has been recently reported.

PMID- 19766457
TI  - Differential sex effects of nutritional status on inflammatory periodontal
      disease in non-human primates.

PMID- 19766458
TI  - Brain stimulation for surgical epilepsy.
AB  - Direct brain stimulation is an emerging treatment of epilepsy especially in
      patients that are not candidates for epilepsy surgery. Several different
      approaches of brain stimulation in epilepsy have been developed: stimulation is
      applied to interrupt epileptic networks in subcortical structures or a stimulus
      is directly applied to the seizure onset zone. Scheduled stimulation targets
      mainly subcortical structures like the anterior thalamic nucleus or the
      centromedian nucleus of the thalamus. The anterior nucleus of the thalamus was
      studied in a randomized trial in humans. Several case series reported reduction
      of seizures targeting other subcortical structures. Scheduled stimulation of the
      seizure onset zone in the hippocampus has also been shown to be safe and
      effective in a small number of patients. The application of electrical pulses to
      test for certain brain functions has long been established for the purposes of
      brain mapping. Traditionally stimulation at 50Hz for several seconds has been
      used. This stimulus frequently causes afterdischarges or seizures.
      Afterdischarges can be terminated by applying a very brief stimulus at the same
      frequency. Responsive stimulation is based on detection on this principle.
      Seizures are recorded intracranially and a high-frequency pulse applied whenever
      seizures evolve electrically. An automated implanted device for seizures
      detection and stimulation has been developed and shown to be safe for human use.
      A large clinical trial is currently ongoing. In conclusion, the optimal target
      and mode of stimulation for the treatment of epilepsy remains under investigation
      and requires large and costly controlled trials.

PMID- 19766459
TI  - The effects of antipsychotic medications on emotion perception in patients with
      chronic schizophrenia in the CATIE trial.
AB  - Few pharmacological intervention studies have examined the impact of medication
      on social cognition, particularly emotion perception. The goal of this
      randomized, double-blind study is to compare the effects of several second
      generation antipsychotics and a first generation antipsychotic, perphenazine, on
      emotion perception in individuals with schizophrenia. Patients were assigned to
      receive treatment with olanzapine, queitapine fumarate, risperidone, ziprasidone
      or perphenazine for up to 18 months. Eight hundred and seventy three patients
      completed an emotion perception test immediately prior to randomization and after
      2 months of treatment. We also examined baseline predictors of emotion perception
      change. Most treatments were associated with a small, non-statistically
      significant improvement in emotion perception at two months, although they did
      not differ from one another. Greater improvement in emotion perception at 2
      months was significantly predicted by lower baseline emotion perception and
      higher baseline neurocognitive functioning, and marginally predicted by less time
      on an antipsychotic.

PMID- 19766460
TI  - Decreased cardiac MIBG uptake, its correlation with clinical symptoms in dementia
      with Lewy bodies.
AB  - Recent studies have demonstrated the usefulness of 123I-meta-iodobenzylguanidine
      (MIBG) myocardial scintigraphy for the diagnosis of dementia with Lewy bodies
      (DLB). In this study, we investigated the relationship between decreased cardiac
      MIBG uptake and clinical symptoms in DLB. Thirty-six patients with probable DLB
      and six normal controls underwent MIBG scintigraphy. We measured the early and
      delayed heart-to-mediastinum (H/M) ratios, and the results between subgroups
      based on the presence and absence of clinical symptoms were compared. The mean
      early and delayed H/M ratios were 1.55+/-0.29 and 1.42+/-0.30, and 30 (83.3%) and
      33 (91.7%) subjects showed lower values compared to the cutoff, respectively. A
      statistically significant difference was found only between groups with and
      without orthostatic hypotension (OH). Among 10 DLB subjects without Parkinsonism,
      nine patients had a decreased H/M ratio in the delayed image. To our knowledge,
      this is the first study to correlate decreased MIBG uptake with the clinical
      symptoms of DLB, and to show a significantly lower H/M ratio in subjects with OH.
      Furthermore, we found that MIBG scintigraphy could detect cardiac sympathetic
      denervation regardless of clinically evident Parkinsonism. These results suggest
      that MIBG myocardial scintigraphy could be a valuable diagnostic test in the
      clinical diagnosis of DLB.

PMID- 19766461
TI  - A study on the adsorption characteristics of an amphiphilic phenothiazine drug on
      activated charcoal in the presence of surfactants.
AB  - In this paper the adsorption of amphiphilic phenothiazine drug Thioridazine
      hydrochloride (THCl) on Activated charcoal (AC) surface was studied in aqueous
      solutions. The effects of different types of surfactants anionic sodium
      dodecylsulfate (SDS) and lithium dodecylsulfate (LiDS), cationic cetyltrimethyl
      ammonium bromide (CTAB) and nonionic TritonX-100 (TX-100) micelles on the
      adsorption were reported. It was found that the Langmuir isotherm appears to fit
      the isotherm data better than the Freundlich isotherm. The adsorption of THCl was
      reduced in the presence of cationic CTAB bearing the same charge as THCl while
      presence of SDS and LiDs did not change significantly adsorption capacity of THCl
      on AC except the shape of the isotherm. The presence of TX-100 micelles
      significantly increased adsorption of THCl on AC. Kinetic measurements showed
      that the adsorption equilibrium of THCl was attained within 30 min in aqueous
      media while in the presence of 10mM anionic micelles the adsorption equilibrium
      of THCl reached the equilibrium almost in 1 min. The kinetics of adsorption in
      view of three kinetic models i.e. the first-order Lagergren model, the pseudo
      second-order model and the intraparticle diffusion model has been discussed. The
      adsorption rate constants of THCl onto AC in the presence of anionic micelles are
      higher than in aqueous media for both kinetics models and the second-order model
      provides the best correlation of data in the absence and presence of micelles. In
      order to gain further insight into the adsorption mechanism of THCl on AC,
      association of THCl with surfactants was also studied by absorption spectra.
      Binding constants of THCl to micelles were calculated by means of Benesi
      Hildebrand Equation to provide more precise comparison of the effect of
      surfactants on the adsorption of THCl.

PMID- 19766462
TI  - The mechanism of erythrocyte sedimentation. Part 2: The global collapse of
      settling erythrocyte network.
AB  - Results reported in the companion paper showed that erythrocytes in quiescent
      blood are combined into a network followed by the formation of plasma channels
      within it. This study is focused on structural changes in the settling dispersed
      phase subsequent to the channeling and the effect of the structural organization
      on the sedimentation rate. It is suggested that the initial, slow stage of
      erythrocyte sedimentation is mainly controlled by the gravitational compactness
      of the collapsed network. The lifetime of RBC network and hence the duration of
      the slow regime of erythrocyte sedimentation decrease with an increase in the
      intercellular pair potential and with a decrease in Hct. The gravitational
      compactness of the collapsed network causes its rupture into individual
      fragments. The catastrophic collapse of the network transforms erythrocyte
      sedimentation from slow to fast regime. The size of RBC network fragment is
      insignificantly affected by Hct and is mainly determined by the intensity of
      intercellular attractive interactions. When cells were suspended in the weak
      aggregating medium, the Stokes radius of fragments does not differ measurably
      from that of individual RBCs. The proposed mechanism provides a reasonable
      explanation of the effects of RBC aggregation, Hct and the initial height of the
      blood column on the delayed erythrocyte sedimentation.

PMID- 19766463
TI  - Polymeric effects on DNA condensation by cationic polymers observed by atomic
      force microscopy.
AB  - Compaction of DNA by condensing agents can provide insights into DNA assembly
      processes, which is keenly related to the essence of gene transfection and gene
      therapy in vivo. In this paper, the morphology of different cationic polymer/DNA
      complexes was studied by using atomic force microscopy (AFM), which is keen to
      the mechanism of DNA condensation induced by amine-based cationic block
      copolymers with poly(poly(ethylene glycol) methyl ether methacrylate). It is
      found that the structures and dimensions of condensing agent/DNA complexes are
      sensitively dependent on the condensing agents. The size of DNA aggregates can be
      affected appreciably by polymers rather than monomers. The amount of nitrogen
      elements per polymer unit, rather than the molecular weights of polymers, appears
      to be more effective on the dimension of the condensates. The impact of the
      copolymer chain structures on the DNA aggregates indicates an effective venue for
      regulating the dimensions and structures of the DNA condensates, which is
      beneficial for optimizing delivery systems for gene transfection.

PMID- 19766464
TI  - Adsorption of octanoic acid at the water/oil interface.
AB  - Fats are widely present in a large variety of food and represent the main source
      of energy for the body. In the current study we investigate the behaviour of
      fatty acids at liquid-liquid interfaces, mimicking some steps of the very complex
      digestion process. Octanoic acid is used as an example of middle chain fatty
      acids. For the oil phase we choose sunflower oil as an industrial product and
      hexane as pure oil. The influence of the fatty acid concentration and the pH of
      the aqueous phase on the interfacial tension is determined by profile analyse
      tensiometry (PAT), which allows to examine the way of adsorption and transition
      of the fatty acids from one phase to the other. Predominantly, the pH affects the
      dissociation and thereby the strength of the hydrophilic character of the fatty
      acid. The adsorption behaviour indicates the different interfacial activity of
      the studied octanoic acid.

PMID- 19766465
TI  - The mechanism of erythrocyte sedimentation. Part 1: Channeling in sedimenting
      blood.
AB  - Despite extensive efforts to elucidate the mechanism of erythrocyte
      sedimentation, the understanding of this mechanism still remains obscure. In
      attempt to clarify this issue, we studied the effect of hematocrit (Hct) on the
      complex admittance of quiescent blood measured at different axial positions of
      the 2 mm x 2 mm cross-section chambers. It was found that after the aggregation
      process is completed, the admittance reveals delayed changes caused by the
      formation of cell-free zones within the settling dispersed phase. The delay time
      (tau(d)) correlates positively with Hct and the distance between the axial
      position where measurements were performed and the bottom and is unaffected by
      the gravitational load. These findings and literature reports for colloidal gels
      suggest that erythrocytes in aggregating media form a network followed by the
      formation of plasma channels within it. The cell-free zones form initially near
      the bottom and then propagate toward the top until they reach the plasma/blood
      interface. These channels increase the permeability of a network and, as a
      result, accelerate the sedimentation velocity. The energy of the flow field in
      channels is sufficiently strong to erode their walls. The upward movement of
      network fragments in channels is manifested by erratic fluctuations of the
      conductivity. The main conclusion, which may be drawn from the results of this
      study, is that the phase separation of blood is associated with the formation of
      plasma channels within the sedimenting dispersed phase.

PMID- 19766466
TI  - Impact of a thermal treatment at different pH on the adsorption behaviour of
      untreated and enzyme-modified egg yolk at the oil-water interface.
AB  - Adsorption properties of egg yolk proteins were investigated with or without
      enzymatic modification with phospholipase A(2) (PLA(2)) and after a thermal
      treatment at pH 4 and 6.5. Heat treatment was assessed from 60 to 90 degrees C
      resulting in a wide range of protein denaturation degrees, which were correlated
      with the interfacial protein load of emulsion droplets. It was shown that
      denatured proteins, i.e. protein aggregates are able to adsorb at the oil-water
      interface and that, most notably, granule constituents play an important role in
      stabilisation of the oil-water interface at pH 4. Moreover, it was shown that
      after a thermal treatment of untreated egg yolk (not enzyme treated) an even
      higher protein load is reached than when PLA(2)-treated egg yolk is used for
      emulsification. Heat-treated natural egg yolk is therefore supposed to be an
      appropriate alternative for PLA(2)-treated egg yolk for producing stable
      emulsions. The SDS-Page profiles show that the composition of the interfacial
      film is highly influenced by a modification with PLA(2) at pH 4 while at pH 6.5
      the interfacial composition of adsorbed proteins is less influenced.

PMID- 19766467
TI  - Effect of acute and chronic hypertension on short- and long-term spatial and
      avoidance memory in male rats.
AB  - It has been demonstrated that hypertension can lead to coronary heart disease,
      heart failure, stroke, and memory loss. In this study we investigated the effect
      of acute and chronic hypertension on the avoidance and spatial learning and
      memory in rats. The forty male rats were divided into acute hypertensive, chronic
      hypertensive and control for each group rats. Hypertension was induced by Deoxy
      Corticosterone Acetate (DOCA)-salt method. DOCA was injected 30mg/kg of body
      weight subcutaneously, twice a week. These rats received NaCl 1% instead of tap
      water for drinking throughout the experiment. The control group received normal
      saline injection with usual drinking water. Spatial learning and memory was
      investigated by Morris water maze test and passive avoidance learning by Shuttle
      box test in the rats after hypertension induction. Results showed that acute
      hypertension impaired short-term memory in passive avoidance learning. However,
      acute and chronic hypertension did not affect spatial learning and memory. These
      data suggest that simple uncomplicated hypertension does not remarkably alter
      cognition.

PMID- 19766468
TI  - [New bone imaging techniques in children with chronic kidney disease].
AB  - Bone damage in the spectrum of chronic kidney disease - mineral and bone
      disorders (CKD-MBD) represents a daily challenge for pediatric nephrologists. A
      real measurement of bone mineral density (BMD) by Dual X-ray absorptiometry (DXA)
      is currently performed to evaluate bone mass in children. However this technique
      has some limitations. In 2000, the National Institute of Health (NIH) has defined
      new "quality" criteria for the diagnosis of osteoporosis in addition to a
      decreased bone mass. Bone strength actually integrates 2 issues: bone density and
      bone quality (i.e., micro architectural organization, bone turnover,
      mineralization and micro fractures). These "quality" criteria cannot be evaluated
      by DXA. Histomorphometry remains the gold standard to evaluate bone but it is
      rarely performed in clinical practice. New bone imaging techniques have thus been
      developed, leading to an improvement in bone assessment. They are particularly
      challenging in children, whose bones continually grow in size, shape and mass.

PMID- 19766469
TI  - [Treatment of homozygous familial hypercholesterolemia with LDL-apheresis on a 4
      year-old child].
AB  - Homozygous familial hypercholesterolemia (HFH) is a rare genetic disease
      associated with increased atherosclerosis, resulting in premature death near the
      age of 20 years. Treatment requires the LDL-apheresis system. M, born from a
      consanguineous union, suffers from HFH (total-cholesterol=12.29 g/l, LDL
      cholesterol=9.65 g/l). Diet and drug treatment was not associated with decreased
      LDL-cholesterol. At the age of 4.5 years (body weight: 16.7 kg), M began
      treatment with LDL-apheresis. Apheresis treatment was given every 2 weeks using
      the Direct Adsorption of LIpoprotein (DALI system, a process that involves total
      blood filtration. During the first 26 sessions, the mean reduction in LDL
      cholesterol was 67+/-12%, while HDL-cholesterol decreased by only 17+/-11%. Mean
      LDL-cholesterol concentration decreased from 6.54+/-0.93 g/l (before apheresis)
      to 2.21+/-0.95 g/l (after apheresis). Apart from iron deficiency anemia, no major
      side effects were observed. LDL-apheresis using the DALI system is associated
      with significant reductions in LDL-cholesterol (similar to reports from the
      literature) without major side effects, even in a child weighing less than 20 kg.
      A long term, multinational (European) study is needed to confirm these results.

PMID- 19766470
TI  - Effect of vitamin A supplemented diet on calcium oxalate renal stone formation in
      rats.
AB  - OBJECTIVES: To study the effect of a vitamin A supplemented diet on calcium
      oxalate stone formation in rats and to test its expected action in the
      dissolution of renal calculi. MATERIAL AND METHODS: Twenty-four male Wistar rats
      were randomly divided into three groups of eight rats each. The first group
      (group A) received a normal diet for six weeks. The second group (group B) was
      fed a lithogenic diet by the addition of ethylene glycol 0.5% to drinking water
      for three weeks then a normal diet for three weeks. The third group (group C)
      received the same lithogenic diet for three weeks then a vitamin A supplemented
      diet 20 times the normal amount (5.1mg/100g of diet) at the three last weeks. One
      day before the end of treatment, each animal was placed for 24h in metabolic cage
      in order to collect urine samples and determine the urinary parameters. RESULTS:
      The glomerular filtration rate and the urinary excretion of citric acid which
      fell in group B have been restored in group C. CONCLUSIONS: This study shows that
      a vitamin A supplemented diet at the rate of 20 times standard ration could
      improve the renal function by restoring the glomerular filtration rate and by
      increasing the urinary pH and excretion of citric acid.

PMID- 19766471
TI  - Observations on the synaptic ribbon morphology in retinas of two human subjects
      at autopsy.
AB  - Retinal photoreceptor and bipolar cell axon terminals possess synaptic ribbons
      (SR) that aid in the trafficking of synaptic vesicles at active zones. In
      rodents, besides SR, a number of other synaptic elements [e.g., synaptic spheres
      (SS)] are known to appear when exposed to altered ambient illumination. Here, we
      report changes of ribbon shape in photoreceptor and bipolar cell axon terminals
      in retinas of two persons at autopsy who suffered from brain hemorrhage. In both
      subjects, retinal hemorrhage was present in the outer and inner nuclear layers.
      SR were bent or swollen and transformed into SS. A count revealed that about 54
      60% of the photoreceptor axon terminals over the nasal to temporal retina
      possessed SS. They were associated with synaptic triads or remained floating in
      cytoplasm. The bipolar cell axon terminals possessed either SR or sphere-like
      bodies. As these features were not seen in control retinas of donors who died of
      other causes, we assume that in hemorrhagic subjects, SR underwent transformation
      into SS, in which perhaps ischemia (caused due to vascular obstructions by
      hemorrhage) played a leading role.

PMID- 19766472
TI  - Immune reconstitution after haematopoietic stem cell transplantation: obstacles
      and anticipated progress.
AB  - Improvement of immune reconstitution after haematopoietic stem cell
      transplantation (HSCT) is a key issue determining the clinical outcome of this
      widely used therapeutic approach. To this end, new strategies have been prompted
      by recent discoveries in immunology. In the setting of human leukocyte antigen
      (HLA) geno(pheno)identical HSCT, better prevention and treatment of acute and
      chronic graft-versus-host disease (GvHD) could significantly attenuate the thymic
      epithelium damage responsible for delayed and incomplete T-cell reconstitution.
      In a haploidentical setting, methods that would significantly accelerate
      neothymopoiesis in the months following injection of highly purified CD34+ cells
      are warranted. If these objectives could be achieved, the haploidentical
      procedure would become more readily available to patients affected by acquired or
      inherited disorders of the haematopoietic system.

PMID- 19766473
TI  - Chylothorax: aetiology, diagnosis and therapeutic options.
AB  - Chylothorax is a rare condition that results from thoracic duct damage with chyle
      leakage from the lymphatic system into the pleural space, usually on the right
      side. It has multiple aetiologies and is usually discovered after it manifests
      itself as a pleural effusion. Diagnosis involves cholesterol and triglyceride
      measurement in the pleural fluid. Complications include malnutrition,
      immunosuppression and respiratory distress. Treatment may be either conservative
      or aggressive depending on the clinical scenario. In this review, we discuss the
      aetiology, diagnosis and treatment of chylothorax. English language publications
      in MEDLINE and references from relevant articles from January 1, 1980 to February
      28, 2008 were reviewed. Keywords searched were chylothorax, aetiology, diagnosis
      and treatment.

PMID- 19766474
TI  - Expanding the reach of harm reduction in Thailand: experiences with a drug user
      run drop-in centre.
AB  - BACKGROUND: Despite an ongoing epidemic of HIV among Thai people who inject drugs
      (IDU), Thailand has failed to implement essential harm reduction programmes. In
      response, a drug user-led harm reduction centre opened in 2004 in an effort to
      expand reduction programming in Thailand. METHODS: We examined experiences with
      the Mitsampan Harm Reduction Centre (MSHRC) among IDU participating in the
      Mitsampan Community Research Project (Bangkok). Multivariate logistic regression
      was used to identify factors associated with MSHRC use. We also examined services
      used at and barriers to the MSHRC. RESULTS: 252 IDU participated in this study,
      including 66 (26.2%) females. In total, 74 (29.3%) participants had accessed the
      MSHRC. In multivariate analyses, MSHRC use was positively associated with
      difficulty accessing syringes (Adjusted Odds Ratio [AOR]=4.05; 95% Confidence
      Interval [CI]: 1.67-9.80), midazolam injection (AOR=3.25; 95%CI: 1.58-6.71),
      having greater than primary school education (AOR=1.88; 95%CI: 1.01-3.52), and
      was negatively associated with female gender (AOR=0.20; 95%CI: 0.08-0.50). Forms
      of support most commonly accessed included: syringe distribution (100%), food and
      a place to rest (83.8%), HIV education (75.7%), and safer injecting education
      (66.2%). The primary reason given for not having accessed the MSHRC was "didn't
      know it existed." CONCLUSION: The MSHRC is expanding the scope of harm reduction
      in Thailand by reaching IDU, including those who report difficulty accessing
      sterile syringes, and by providing various forms of support. In order to maximise
      its benefits, efforts should be made to increase awareness of the MSHRC, in
      particular among women.

PMID- 19766475
TI  - Factors affecting sodium hypochlorite extraction of CCA from treated wood.
AB  - Significant amounts of chromated copper arsenate (CCA) treated wood products,
      such as utility poles and residential construction wood, remain in service. There
      is increasing public concern about environmental contamination from CCA-treated
      wood when it is removed from service for reuse or recycling, placed in landfills
      or burned in commercial incinerators. In this paper, we investigated the effects
      of time, temperature and sodium hypochlorite concentration on chromium oxidation
      and extraction of chromated copper arsenate from CCA-treated wood (Type C)
      removed from service. Of the conditions evaluated, reaction of milled wood with
      sodium hypochlorite for one hour at room temperature followed by heating at 75
      degrees C for two hours gave the highest extraction efficiency. An average of 95%
      Cr, 99% Cu and 96% As could be removed from CCA-treated, milled wood by this
      process. Most of the extracted chromium was oxidized to the hexavalent state and
      could therefore be recycled in a CCA treating solution. Sodium hypochlorite
      extracting solutions could be reused several times to extract CCA components from
      additional treated wood samples.

PMID- 19766476
TI  - Human papilloma virus in head and neck cancer: the need for a standardised assay
      to assess the full clinical importance.
AB  - Recent studies have revealed an important and intriguing role for human
      papillomavirus (HPV) in head and neck squamous cell carcinoma (HNSCC). There are
      indications that the prevalence of HPV-positive HNSCC has recently increased, and
      genetic analyses point to a completely distinct class of HNSCCs. Most studies
      suggest that patients with this type of tumour have a better prognosis and some
      argue that an adjusted therapeutic approach is needed. One crucial point in the
      research of HNSCC-HPV involvement has often been neglected, which is the lack of
      a standardised assay to detect HPV. This has resulted in a considerable variation
      in the frequency of HPV-positive tumours between studies reported thus far.
      Especially for PCR-based tests, the risk exists that the assay is too sensitive
      and detects virus without implying a causal involvement in HNSCC. A reliable
      algorithm to detect a clinically relevant HPV infection in formalin-fixed
      paraffin embedded tissue has recently become available. Here, we address
      important biological and analytical aspects of HPV involved in the development of
      HNSCC and it is emphasised that a standardised HPV assay is a prerequisite for
      assessing the clinical importance of a HPV infection in HNSCC.

PMID- 19766477
TI  - Polymorphisms in telomere-associated genes, breast cancer susceptibility and
      prognosis.
AB  - Telomeres are essential structures for maintaining chromosomal stability and
      their length has been reported to correlate with cancer risk and clinical
      outcome. Single nucleotide polymorphisms (SNPs) in genes encoding telomere
      associated proteins could affect telomere length and chromosomal stability by
      influencing gene expression or protein configuration in the telomeres. Here, we
      report the results of the first association study on genetic variation in
      telomere-associated genes and their effect on telomere length, breast cancer (BC)
      susceptibility and prognosis. We genotyped 14 potentially functional and most
      informative SNPs in nine telomere-associated genes (TERT, TEP1, TERF1, TERF2,
      TERF2IP, ACD, POT1, TNKS and TNKS2) in 782 incident BC cases and 1559 matched
      controls. Relative telomere length (RTL) varied statistically significantly
      between the genotypes of the SNPs rs446977 (TEP1, p=0.04), rs938886 (TEP1,
      p=0.04) and rs6990097 (TNKS, p=0.04). However, none of them was associated with
      BC susceptibility and only rs6990097 correlated with regional lymph node
      metastasis (odds ratio (OR) 1.38, 95% confidence interval (CI) 1.08-1.77). The
      strongest association with BC susceptibility was observed for rs3785074 (TERF2,
      OR 0.51, 95% CI 0.31-0.83) and rs10509637 (TNKS2, OR 1.33, 95% CI 1.08-1.62).
      Haplotype and diplotype analysis confirmed the association of the TNKS2 gene with
      BC susceptibility. rs3785074 (TERF2) was additionally associated with histologic
      grade (OR 1.44, 95% CI 1.08-1.92) and negative oestrogen receptor status (OR
      2.93, 95% CI 1.13-7.58). None of the SNPs showed a significant correlation with
      survival of the breast cancer patients. With these results, none of the SNPs
      represents any valuable prognostic marker for BC.

PMID- 19766478
TI  - Optimisation of a green gas supply chain--a review.
AB  - In this review the knowledge status of and future research options on a green gas
      supply based on biogas production by co-digestion is explored. Applications and
      developments of the (bio)gas supply in The Netherlands have been considered,
      whereafter literature research has been done into the several stages from
      production of dairy cattle manure and biomass to green gas injection into the gas
      grid. An overview of a green gas supply chain has not been made before. In this
      study it is concluded that on installation level (micro-level) much practical
      knowledge is available and on macro-level knowledge about availability of
      biomass. But on meso-level (operations level of a green gas supply) very little
      research has been done until now. Future research should include the modeling of
      a green gas supply chain on an operations level, i.e. questions must be answered
      as where to build digesters based on availability of biomass. Such a model should
      also advise on technology of upgrading depending on scale factors. Future
      research might also give insight in the usability of mixing (partly upgraded)
      biogas with natural gas. The preconditions for mixing would depend on composition
      of the gas, the ratio of gases to be mixed and the requirements on the mixture.

PMID- 19766479
TI  - Enhancement of enzymatic accessibility by fibrillation of woody biomass using
      batch-type kneader with twin-screw elements.
AB  - Fibrillation of wood cell walls into submicron and/or nanoscale fibers was
      successfully carried out in the presence of water by using a batch-type kneader
      with combination-available twin-screw elements. The results obtained are expected
      to be used for the application of a twin-screw extruder. Two types of screw
      combinations were used for applying different shearing and distribution forces.
      Most of the fibers of the fibrillated products had diameters less than 1 microm,
      and some of them had diameters less than 100 nm. The maximum glucose yield by
      enzymatic saccharification was found to be 54.2% in the fibrillated products
      kneaded for 20 min after ball milling for 20 min using a screw combination for
      applying high shearing force. The fibrillation increased the surface area of
      cellulose. The glucose yield was improved by cooking the fibrillated products
      with water at 135 degrees C under 0.25 MPa, revealing that only mechanical
      kneading appears to have some limitation to expose cellulose for complete
      enzymatic saccharification.

PMID- 19766480
TI  - Acid hydrolysis of sugarcane bagasse for lactic acid production.
AB  - In order to use sugarcane bagasse as a substrate for lactic acid production,
      optimum conditions for acid hydrolysis of the bagasse were investigated. After
      lignin extraction, the conditions were varied in terms of hydrochloric (HCl) or
      sulfuric (H(2)SO(4)) concentration (0.5-5%, v/v), reaction time (1-5h) and
      incubation temperature (90-120 degrees C). The maximum catalytic efficiency (E)
      was 10.85 under the conditions of 0.5% of HCl at 100 degrees C for 5h, which the
      main components (in gl(-1)) in the hydrolysate were glucose, 1.50; xylose, 22.59;
      arabinose, 1.29; acetic acid, 0.15 and furfural, 1.19. To increase yield of
      lactic acid production from the hydrolysate by Lactococcus lactis IO-1, the
      hydrolysate was detoxified through amberlite and supplemented with 7 g l(-1) of
      xylose and 7 g l(-1) of yeast extract. The main products (in gl(-1)) of the
      fermentation were lactic acid, 10.85; acetic acid, 7.87; formic acid, 6.04 and
      ethanol, 5.24.

PMID- 19766481
TI  - Chemical composition and pulping of date palm rachis and Posidonia oceanica--a
      comparison with other wood and non-wood fibre sources.
AB  - In the present paper, the valorisation of two residues: Posidonia oceanica and
      date palm rachis was investigated. First, their chemical composition was studied
      and showed that they present amounts of holocellulose, lignin and cellulose
      similar to those encountered in softwood and hardwood. Extractives in different
      solvents and ash contents are relatively high. Moreover, ash composition
      assessment showed that silicon is the major component (17.7%) for P. oceanica.
      The high ash quantity and the low DP (about 370) may be considered as serious
      disadvantages of P. oceanica, in the pulping and papermaking context. Oppositely,
      the properties of rachis date palm and those of the ensuing pulp, obtained from a
      classical soda-anthraquinone cooking, demonstrated the suitability of this
      agricultural by-product for papermaking. Preliminary tests conducted on unrefined
      pulp suspensions and handsheets from date palm rachis in terms of freeness, Water
      Retention Value and mechanical properties allowed confirming the good quality of
      date palm rachis fibres.

PMID- 19766482
TI  - Medium-density particleboards from modified rice husks and soybean protein
      concentrate-based adhesives.
AB  - The main goal of this work was to evaluate the technical feasibility of using
      rice husk (RH) as wood substitute in the production of environmentally sound
      medium-density particleboards using adhesives from soybean protein concentrate
      (SPC). Chemical modification of rice husk with sodium hydroxide and sodium
      hydroxide followed by hydrogen peroxide (bleaching) were undertaken to evaluate
      the effect of such treatments on the composition and topology of rice husk and
      the performance of produced panels. Both treatments were efficient in partially
      eliminating hemicelluloses, lignin and silica from RH, as evidenced by thermo
      gravimetric analysis (TGA). Scanning electron microscopy observations suggested
      that alkaline treatment resulted in a more damaged RH substrate than bleaching.
      The dependence of mechanical properties (modulus of rupture, modulus of
      elasticity, and internal bond) and the physical properties (water absorption and
      thickness swelling) on chemical treatments performed on both, rice husk and SPC
      was studied. Bleached-rice husk particleboards bonded with alkaline-treated
      soybean protein concentrate displayed the best set of final properties.
      Particleboards with this formulation met the minimum requirements of internal
      bond, modulus of elasticity and modulus of rupture recommended by the US Standard
      ANSI/A208.1 specifications for M1, MS and M2-grade medium-density particleboards,
      but failed to achieve the thickness swelling value recommended for general use
      panels. This limitation of soybean protein concentrate-bonded rice husk
      particleboards was counterbalanced by the advantage of being formaldehyde-free
      which makes them a suitable alternative for indoor applications.

PMID- 19766483
TI  - Transesterification of sunflower oil to biodiesel on ZrO2 supported La2O3
      catalyst.
AB  - ZrO(2) supported La(2)O(3) catalyst prepared by impregnation method was examined
      in the transesterification reaction of sunflower oil with methanol to produce
      biodiesel. It was found that the catalyst with 21 wt% loaded La(2)O(3) and
      calcined at 600 degrees C showed the optimum activity. The basic property of the
      catalyst was studied by CO(2)-TPD, and the results showed that the fatty acid
      methyl ester (FAME) yield was related to their basicity. The catalyst was also
      characterized by TG-DTA, XRD, FTIR, SEM and TEM, and the mechanism for the
      formation of basic sites was discussed. It was also found that the crystallite
      size of support ZrO(2) decreased by loading of La(2)O(3), and the model of the
      solid-state reaction on the surface of La(2)O(3)/ZrO(2) catalyst was proposed.
      Besides, the influence of various reaction variables on the conversion was
      investigated.

PMID- 19766484
TI  - Impact of corn stover composition on hemicellulose conversion during dilute acid
      pretreatment and enzymatic cellulose digestibility of the pretreated solids.
AB  - This study assessed the impact of corn stover compositional variability on xylose
      conversion yields during dilute acid pretreatment and on enzymatic cellulose
      digestibility of the resulting pretreated solids. Seven compositionally-different
      stovers obtained from various locations throughout the United States were
      pretreated at three different conditions in triplicate in a pilot-scale
      continuous reactor. At the same pretreatment severity, a 2-fold increase in
      monomeric xylose yield and a 1.5-fold increase in enzymatic cellulose
      digestibility from their lowest values were found. Similar results were observed
      at the other pretreatment conditions. It was found that xylose conversion yields
      decreased with increasing acid neutralization capacity or soil content of the
      corn stover. Xylose yields also increased with increasing xylan content. No other
      significant correlations between corn stover's component concentrations and
      conversion yields were found.

PMID- 19766485
TI  - Identification of fungi associated with municipal compost using DNA-based
      techniques.
AB  - Fungi are important in terrestrial decay processes. However, fungi associated
      with organic decay during composting are still not well known. In this study
      culture-independent methods were used to identify fungi associated with
      composting organic municipal wastes to gain a better understanding of the
      diversity of fungi associated with this process. Fungal communities from 0, 210,
      and 410day-old compost samples were assessed with DNA fingerprinting using
      denaturing gradient gel electrophoresis (DGGE) and by the analysis of DNA
      sequences from rDNA clone libraries. From 207 rDNA sequences, 82 fungal OTU's
      were detected. A disproportionate number of yeast sequences were detected in Day
      0 clone libraries, including the human pathogens Candida tropicalis and Candida
      krusei (Saccharomycetales). Basidiomycetes accounted for over half of the clones
      from the Day 210 sample. Clones of Cercophora and Neurospora species accounted
      for most of the fungal clones of the Day 410 sample. No Zygomycetes or
      Aspergillus species were detected in this study. These findings call for a
      reassessment of long held views about the organisms involved in the composting of
      organic municipal wastes.

PMID- 19766486
TI  - Two-phase (acidogenic-methanogenic) anaerobic thermophilic/mesophilic digestion
      system for producing Class A biosolids from municipal sludge.
AB  - Two different arrangements of two-phase anaerobic sludge systems were operated
      treating a mixture of primary and secondary sludge. Two steady state periods were
      evaluated: the first acidogenic thermophilic phase was operated at hydraulic
      retention times of 3 and 2 days and the second methanogenic (mesophilic and
      thermophilic) phases at 13 and 10 days. The two-phase systems had an efficient
      removal of pathogens and parasites, achieving values lower than those specified
      for Class A biosolids, according to the Mexican Standard NOM-004-SEMARNAT-2002.
      The first thermophilic phase achieved almost complete destruction of pathogens
      and parasites by itself. During the second steady state period, volatile fatty
      acids accumulated in the second methanogenic phases (HRT of 10 days and an
      organic load of 3 kg VS/m(3)d) indicating that the systems were overloaded,
      mainly the mesophilic digester. In this case, the accumulation of propionic acid
      may be related to a deficiency of micronutrients. The results show that the two
      phase thermophilic/mesophilic anaerobic sludge digestion may be considered as an
      adequate option for the production of Class A biosolids.

PMID- 19766487
TI  - Life-cycle energy and environmental analysis of bioethanol production from
      cassava in Thailand.
AB  - In this study, the life-cycle energy and environmental assessment was conducted
      for bioethanol production from cassava in Thailand. The scope covered all stages
      in the life cycle of bioethanol production including cultivating, chip
      processing, transportation and bioethanol conversion. The input-output data were
      collected at plantation sites and ethanol plants which included materials usage,
      energy consumption, and all emissions. From the energy analysis, the results show
      that cassava-based bioethanol has a negative net energy value with an energy
      ratio was less than 1, indicating a net energy loss. For the environmental
      performance, the results show that throughout the life cycle of bioethanol, the
      conversion stage contributes most to the environmental impacts which is due to
      the use of coal for power and steam production in the bioethanol plants. It is
      suggested that a partial substitution of coal with biogas produced from existing
      wastewater treatment could lead to a significant reduction in the environmental
      impact.

PMID- 19766488
TI  - Special issue on the Challenges in Environmental Science and Engineering, CESE
      2009 14-17 July, 2009--Jupiters Hotel, Townsville, Queensland, Australia.

PMID- 19766489
TI  - Bioenergy and products from thermal pyrolysis of rice straw using plasma torch.
AB  - The aim of this work was to study the feasibility and operation performance of
      plasma torch pyrolysis of biomass wastes, taking rice straw as the target
      material. This novel method has several advantages including high heating rate,
      short heating time, no viscous tar and low residual char (7.45-13.78 wt.%) or
      lava. The productions of CO and H(2) are the major components (91.85-94.14 vol.%)
      in the gas products with relatively high reaction rates. The maximum
      concentrations of gaseous products occurring times are all below 1 min. Almost
      90% of gaseous products were appeared in 4 min reaction time. The yield of H(2)
      increases with the increase of input power or temperature. With the increase of
      moisture (5-55 wt.%), the mass yields of H(2) and CO(2) also increase from the
      H(2)O decomposition. However, due to the CO(2) production, the accumulated volume
      fraction of syngas decreases with the increase of moisture.

PMID- 19766490
TI  - Production and characterization of an intracellular bioflocculant by
      Chryseobacterium daeguense W6 cultured in low nutrition medium.
AB  - A novel intracellular bioflocculant (named MBF-W6) produced by Chryseobacterium
      daeguense W6 cultured in low nutrition medium was investigated in this study. The
      effects of carbon source, nitrogen source, C/N ratio, initial pH, inoculum size,
      culture temperature and shaking speed on MBF-W6 production were studied. Chemical
      analysis showed that the purified MBF-W6 was mainly composed of 32.4% protein,
      13.1% polysaccharide and 6.8% nucleic acid. Fourier-transform infrared (FTIR)
      spectroscopy indicated the presence of carboxyl, hydroxyl, and methoxyl groups.
      The elemental analysis of purified MBF-W6 revealed that the mass proportion of C,
      H, O, N and S was 40.92:6.53:44.01:8.53:1.01 (w/w) correspondingly. MBF-W6 had
      good flocculating rate in Kaolin suspension without any cation addition. The
      highest flocculating rate of 96.9% was achieved under the optimal conditions
      (bioflocculant dosage 1.2 mg l(-1), pH 5.6 and temperature 15 degrees C).

PMID- 19766491
TI  - The Kindlin protein family: new members to the club of focal adhesion proteins.
AB  - Kindlins are a group of proteins that have recently attracted attention for their
      ability to bind and activate integrins. Moreover, they have also been linked to
      inherited and acquired human diseases including Kindler syndrome, leukocyte
      adhesion deficiency, and cancer. Although most studies have focused on kindlins
      as key regulatory components of cell-extracellular matrix junctions such as focal
      adhesions, preliminary data suggest the involvement of additional cellular
      compartments in mediating their functions, particularly at cell-cell contacts and
      the nucleus. Investigating the many roles of kindlins is likely to expand and
      sharpen our view on the versatility of integrin-mediated cell adhesion, the
      nuclear function of focal adhesion proteins, and the crosstalk between cell-cell
      and cell-matrix adhesions in health and disease.

PMID- 19766492
TI  - Establishing nitrogen-fixing symbiosis with legumes: how many rhizobium recipes?
AB  - Rhizobia are phylogenetically disparate alpha- and beta-proteobacteria that have
      achieved the environmentally essential function of fixing atmospheric nitrogen
      (N(2)) in symbiosis with legumes. All rhizobia elicit the formation of root - or
      occasionally stem - nodules, plant organs dedicated to the fixation and
      assimilation of nitrogen. Bacterial colonization of these nodules culminates in a
      remarkable case of sustained intracellular infection in plants. Rhizobial
      phylogenetic diversity raised the question of whether these soil bacteria shared
      a common core of symbiotic genes. In this article, we review the cumulative
      evidence from recent genomic and genetic analyses pointing toward an unexpected
      variety of mechanisms that lead to symbiosis with legumes.

PMID- 19766493
TI  - Bilateral bulbar palsy and postural hypotension following surgery for fourth
      ventricle subependymoma.
AB  - We report a 54-year-old man who developed bilateral bulbar palsy and severe
      postural hypotension following resection of a fourth ventricle subependymoma. It
      is proposed that interruption of the function of the nucleus of the tractus
      solitarius (in which the baroreflex is integrated) may have been responsible for
      the postural hypotension.

PMID- 19766494
TI  - Comment on "Asystole due to trigemino-cardiac reflex: A rare complication of
      trans-sphenoidal surgery for pituitary adenoma".

PMID- 19766495
TI  - A hemispherotomy for intractable startle epilepsy characterized by infantile
      hemiplegia and drop attacks.
AB  - Startle epilepsy is provoked by unexpected sensory stimuli, mainly auditory, and
      reveals subsequent tonic posturing of the limbs. We present a case of intractable
      startle epilepsy with infantile hemiplegia and discuss the indications for a
      hemispherotomy.

PMID- 19766496
TI  - Septo-optic dysplasia with encephalocele.
AB  - Septo-optic dysplasia is a rare congenital anomaly presenting with visual
      deficits or pituitary dysfunction. We report the first case of septo-optic
      dysplasia associated with encephalocele, partial callosal agenesis,
      polymicrogyria and subcortical nodular heterotopia.

PMID- 19766497
TI  - Interdural giant dermoid cyst of the petrous apex.
AB  - Dermoid cysts account for less than 1% of all intracranial neoplasms and these
      are principally situated close to the midline. Those located at the petrous apex
      are generally in the intradural, and less frequently in the interdural,
      compartment. We report a 37-year-old woman with a giant interdural dermoid cyst
      of the petrous apex, associated with erosion of the middle fossa floor, and
      review the relationships of these dysembryogenic lesions, the dura mater and the
      neurovascular structures of this complex anatomical region, along with the
      relevant literature.

PMID- 19766498
TI  - Quantitative analysis of iron concentration and expression of ferroportin 1 in
      the cortex and hippocampus of rats induced by cerebral ischemia.
AB  - Iron overload induced by brain ischemia has been shown to be involved in
      neurodegenerative disease. Little is known about the relationship between brain
      ischemia and ferroportin 1 (FP1). The aims of this study are: (i) to determine
      whether iron accumulation in the brain is induced by cerebral hypoperfusion; and
      (ii) to test whether expression of FP1 is influenced by cerebral ischemia. The
      common carotid arteries (CCA) of rats were ligated bilaterally to induce cerebral
      ischemia, and the iron concentration of the cortex and hippocampus was measured
      by graphite furnace atomic absorption spectrometry. Iron was stained by Perl's
      method. The expression of FP1 mRNA and protein was shown by the reverse
      transcriptase polymerase chain reaction and immunohistochemical methods. The iron
      concentration in the cortex and hippocampus of ischemic rats had increased on day
      7 (CCA7) and significantly on day 28 (CCA28) compared to control rats. More iron
      granules had been deposited in the cerebral cortex and hippocampus in rats with
      bilaterally ligated CCA on CCA7 and CCA28. In ischemic rats, FP1 expression in
      the cerebral cortex and hippocampus was decreased by CCA7 and this was more
      marked by CCA28 compared to control rats. We therefore concluded that iron
      deposition in the cerebral cortex and hippocampus of rats is induced by cerebral
      ischemia. Iron deposition may be attributed to the decrease in FP1 expression,
      and this inhibition of FP1 expression could be a major contributor to the
      formation of iron deposits in cerebral ischemia.

PMID- 19766499
TI  - Very late thrombosis in a patient with a drug-eluting stent for intracranial
      atherosclerotic stenosis.
AB  - Late stent thrombosis is an infrequent, but severe, complication after
      implantation of a drug-eluting stent. We report one such patient, a 69-year-old
      man with intracranial vertebral artery stenosis. He experienced very late stent
      thrombosis after discontinuation of clopidogrel therapy, about 16 months after
      the insertion of a Taxus Stent (Boston Scientific Corporation, Natick, MA, USA).
      The patient recovered well, with good clinical outcome, after the re-initiation
      of dual antiplatelet and anticoagulation therapy. No abnormality within the stent
      was identified on a repeat angiogram taken 4 weeks after treatment re-initiation.

PMID- 19766500
TI  - Immunohistochemical findings of multiple ossified en plaque meningiomas in the
      thoracic spine.
AB  - We describe a 76-year-old woman who presented with painful muscle weakness and
      numbness in both legs secondary to grossly ossified meningiomas at the T8 and T11
      T12 vertebral levels. Midline durotomy followed by en bloc excision of the
      tumours, together with partial resection of the dura mater and the arachnoid, was
      performed. Histopathological examination showed both tumours consisted of three
      different histological patterns: psammomatous, fibrous, and metaplastic subtypes.
      Immunostaining for bone morphogenetic protein-2 and vascular endothelial growth
      factor was significantly positive in the areas surrounding mature bone tissues in
      the metaplastic and psammomatous subtypes.

PMID- 19766501
TI  - Congenital absence of the medial meniscus associated with lipoma arborescens.
AB  - Congenital abnormalities of the medial meniscus are extremely rare and have been
      reported commonly with other deformities. We report an isolated aplasia of the
      medial meniscus. A 37-year-old man presented with a slow-growing painless
      swelling, accompanied by intermittent effusion of his left knee. Magnetic
      resonance imaging demonstrated frond-like proliferations of fatty synovium. He
      was initially diagnosed with synovial chondromatosis, but later found to have
      lipoma arborescens. While an arthroscopic synovectomy was being performed,
      congenital absence of the medial meniscus was discovered as an incidental
      finding.

PMID- 19766502
TI  - Residual atrial septal defect after percutaneous closure with an Amplatzer
      device.

PMID- 19766503
TI  - Influence of two perfusion strategies on oxygen metabolism in paediatric cardiac
      surgery. Evaluation of the high-flow, low-resistance technique.
AB  - OBJECTIVE: Paediatric cardiac surgery is often performed under hypothermic
      conditions, that is, with a reduced core body temperature. Certain interventions
      even require the circulation to be stopped. This can only be done at a body
      temperature of 18 degrees C, with no risk of neurological damage and harm to the
      brain and other organs. Vasoconstriction is a natural reaction of the body to
      cold, causing the blood vessels to contract. Such a reaction would lead to a
      clear rise in blood pressure on cardiopulmonary bypass (CPB). Since the blood
      pressure is regulated in the arteriolar loop of the capillary system, there is a
      marked increase in blood pressure and a suppression of free water into the
      surrounding tissue, which, in turn, may lead to the intra-operative development
      of oedemas. This study aimed to investigate whether the high-flow, low-resistance
      (HFLR) technique offers any benefits over conventional methods. METHOD: This
      open, prospective, randomised study was to recruit 48 children scheduled to
      undergo surgery for congenital heart disease. To investigate the two different
      perfusion strategies, we have measured intestinal perfusion as well as skin
      perfusion with laser Doppler spectroscopy. To identify the effects on the immune
      system, selected immunologic parameters of systemic inflammation were
      additionally measured. Laser Doppler spectroscopy is a method that uses a glass
      fibre probe to determine the parameters of oxygen saturation of haemoglobin and
      relative haemoglobin quantity in an illuminated tissue volume, as well as the
      perfusion parameters of relative blood flow and blood flow velocity in the sample
      volume of the probe. RESULTS: During the study period, the change in oxygen
      saturation over time was comparable in both groups. At the end of surgery, the
      patients of the high-flow group had significantly higher saturation levels in the
      intestinal mucosa (p<0.05). Over the course of intensive care, the groups did not
      differ in terms of fluid supply, administration of packed red blood cells,
      platelet concentrates or fresh frozen plasma. Analysis of urinary output revealed
      significant group differences. It was higher in the patients of the high-flow
      group than the normal-flow group (p<0.03), without differences in diuretic
      administration. CONCLUSION: Laser Doppler spectroscopy is highly suited to the
      detection even of the slightest changes in flow characteristics and oxygenation
      of the skin, musculature and intestinal mucosa during surgery with extracorporeal
      circulation using CPB. At the same time, the technique of HFLR perfusion was
      found to have benefits over conventional bypass methods.

PMID- 19766504
TI  - Endoscopic treatment for delayed cardiac tamponade.
AB  - Cardiac tamponade occurring during the late postoperative period after open-heart
      surgery is an extremely serious complication. One surgical therapy is a finger
      dissection through subxiphoid incision. The main limitation is an incomplete view
      into the pericardial sac. To make subxiphoid exploration more effective, we
      developed a novel technique of endoscope-assisted removal of delayed cardiac
      tamponade through subxiphoid pericardiotomy. Surgery was performed under optical
      guidance of an endoscopic retractor routinely used for harvesting saphenous veins
      for bypass grafting. After the subxiphoid pericardiotomy, we introduced the
      endoscopic retractor into the pericardial space, and the haematoma was completely
      evacuated using a suction apparatus and endoscopic forceps. Between January 2008
      and March 2009, three patients underwent endoscope-assisted removal of late
      cardiac tamponade. The haematoma was completely removed without re-sternotomy. No
      bleeding or tamponade occurred following the procedure. An endoscopic approach
      for treating late cardiac tamponade provides the advantages of minimally invasive
      surgery through subxiphoid pericardiotomy combined with an optimal surgical
      perspective. This novel technique permits exploration of the pericardium and
      helps prevent new wounds.

PMID- 19766505
TI  - Assessment of lungs for transplantation: a stepwise analysis of 476 donors.
AB  - OBJECTIVE: This study aims to assess the suitability rates and the causes of lung
      donor refusal, to determine which factors could be improved to expand the donor
      pool available for transplantation (LTx). METHODS: Lung donors offered to our
      Lung Transplantation Unit from October 1993 to December 2007 were reviewed to
      assess the causes of unsuitability. The donor-lung evaluation was divided into
      three stages: stage 1 (PaO(2)/FiO(2) ratio, chest X-ray, bronchoscopic findings),
      stage 2 (donor-lung inspection and palpation) and stage 3 (assessment of grafts
      after harvesting). Variables from donors and recipients were analysed and
      compared between 1993-2001 (group A) and 2002-2007 (group B). An additional
      subgroup of extended donors was analysed to assess the recipient outcomes.
      RESULTS: A total of 476 lung donors were assessed (278 men and 198 women; mean
      age 29+/-13 years). Causes of death were trauma in 255, intracranial bleeding in
      202 and others in 19. As many as 273 donors were suitable for LTx (57%; 162
      double LTx and 111 single LTx). Acceptability rates were 68%, 58% and 57% at
      stages 1, 2 and 3, respectively, and were significantly higher in group B than in
      group A (overall: 64% vs 54%; stage 2: 91% vs 79%), with no changes in stages 1
      and 3. Abnormal bronchoscopy precluded LTx in 79 cases (16%). Group B donors were
      older (p=0.000), ventilated longer (p=0.07) and with shorter ischaemic times
      (p=0.000) than group A. In the recipients, primary graft dysfunction (PGD) (17%
      vs 15%) and 30-day mortality (11% vs 6%) did not differ between both the groups.
      No differences were observed between extended and ideal donors in terms of
      recipient 30-day mortality (extended 6% vs ideal 9%; p=0.315) and development of
      PGD (extended 21% vs ideal 15%; p=0.342). CONCLUSIONS: Despite the high rate of
      organ donation in Spain, the acceptability rate remains low (57%), mainly due to
      failure to meet the criteria for acceptance at the early stages of donor-lung
      assessment. Improvements in multi-organ donor care must be made to expand the
      lung-donor pool. The use of extended donors does not seem to have a negative
      impact on recipient outcomes.

PMID- 19766506
TI  - Neuroprotective effects of erythropoietin during deep hypothermic circulatory
      arrest.
AB  - OBJECTIVE: Permanent mild-to-severe brain injury with neurologic sequelae remains
      a significant source of postoperative morbidity in cardiovascular surgery. There
      is increasing evidence that erythropoietin confers neuroprotective effects in
      various conditions of neuronal damage, such as hypoxia and cerebral ischaemia.
      Using a surviving porcine model, this study evaluates whether systemic treatment
      with erythropoietin induces brain protection in deep hypothermic circulatory
      arrest (DHCA). METHODS: Sixteen pigs (42+/-3 kg) randomly assigned into two
      groups (n=8) were subjected to 60 min of DHCA at an intracerebral temperature of
      20 degrees C. The animals of the erythropietin group were treated perioperatively
      with 500 IU kg(-1) of recombinant human erythropoietin on 3 consecutive days
      beginning the day before surgery. Intracerebral monitoring was performed by
      subcortical microdialysis, brain tissue oxygenation, measurement of brain
      temperature and intracranial pressure. Neurologic recovery was evaluated daily.
      Perioperative S100 beta protein serum level was determined. The brains were
      harvested on the postoperative day 6 after perfusion fixation. Multiple brain
      regions were investigated histologically for hypoxic-ischaemic damage. RESULTS:
      The subcortical brain microdialysis detected significant increase of glycerol and
      lactate concentrations in both groups (P=0.0001) with considerably higher
      concentrations in the brain of control animals (P=0.011). There were no
      significant differences in neurological outcome (P=0.15). Erythropoietin-treated
      animals tended to a more complete and rapid neurological recovery. By contrast,
      none of the animals in the control group achieved complete neurological recovery.
      S100 beta protein as a putative marker of cerebral injury tended to be higher in
      the control group. Brain infarction was detectable in all control animals but
      only in two erythropoietin-treated animals. CONCLUSION: These results suggest
      some beneficial neuroprotective effects of erythropoietin in this model of global
      brain ischaemia induced by 1h of hypothermic circulatory arrest.

PMID- 19766508
TI  - Intrapleural polymeric films containing cisplatin for malignant pleural
      mesothelioma in a rat tumour model: a preliminary study.
AB  - OBJECTIVE: This study aims to investigate the effect of intrapleural polymeric
      films containing cisplatin on the local recurrence of malignant pleural
      mesothelioma in a rat tumour model. METHODS: An orthotopic rat recurrence model
      of malignant pleural mesothelioma was used. Five animals per group were
      evaluated. Polymeric films (4.5 cm diameter) for the local delivery of anticancer
      drug were constructed: hyaluronate, chitosan and the combined dual-layer polymers
      were loaded with cisplatin at a concentration of 100 mgm(-2). Animals without any
      adjuvant therapy were used as control. Mesothelioma cells were injected
      subpleurally in the anaesthetised rats. Six days later, a pleural tumour of 5.5mm
      was resected and a left pneumonectomy and pleural abrasion were performed.
      Thereafter, the cisplatin-loaded and unloaded films or cisplatin solution were
      intrapleurally applied, according to randomisation. After 6 days, animals were
      euthanised and organs harvested for morphological and histological evaluations.
      The primary endpoint was the volume of tumour recurrence. The secondary endpoints
      were treatment-related toxicity; cisplatin serum concentration evaluated at
      different time points; and cisplatin concentration in the pleura measured at
      autopsy. Analysis of variance (ANOVA) was used for statistical analysis.
      Bonferroni correction was applied for comparison between all groups. RESULTS:
      Tumour volume was significantly reduced in the hyaluronate cisplatin and
      hyaluronate-chitosan cisplatin groups in comparison to control groups (p=0.001
      and p<0.0001, respectively). Animals treated with hyaluronate-chitosan cisplatin
      had a tumour recurrence significantly lesser than animals treated with cisplatin
      solution (p=0.003) and hyaluronate cisplatin (p=0.032). No toxicity related to
      the different treatments was observed. On postoperative days 1 and 2, cisplatin
      was detected in the serum at a concentration six- and sevenfold significantly
      higher in the hyaluronate cisplatin and hyaluronate-chitosan cisplatin groups, in
      comparison to cisplatin solution, and was maintained over time. Cisplatin levels
      in the pleura were higher in the hyaluronate-chitosan cisplatin group than in all
      others. CONCLUSIONS: Hyaluronate-chitosan cisplatin was significantly effective
      in reducing tumour recurrence compared with cisplatin solution. Hyaluronate and
      hyaluronate-chitosan loaded with cisplatin assured significantly higher and more
      prolonged plasmatic drug concentrations than cisplatin solution without
      increasing toxicity.

PMID- 19766509
TI  - Independent predictors of postoperative atrial fibrillation.

PMID- 19766510
TI  - Open anastomosis: an alternative for proximal vein graft anastomoses in
      significantly diseased aortas.
AB  - We describe a simple technique of constructing proximal vein graft anastomoses,
      in an open fashion, under brief periods of very low pump flows. We have used this
      technique without complications in more than 100 patients with significantly
      diseased ascending aorta wall. In our opinion, this technique is a good
      alternative to other, more complex, approaches often described.

PMID- 19766511
TI  - Termination of resuscitation: potential benefits of clinical prediction rules.

PMID- 19766512
TI  - Review role of topotecan in gynaecological cancers: current indications and
      perspectives.
AB  - BACKGROUND: Ovarian cancer is the fourth cause of death from gynaecological
      cancer and cervical cancer is the first in women <45 years old in developing
      countries. The aim of this article is to review the role of topotecan (Hycamtin),
      a semi-synthetic alkaloid derivative of camptothecin, in ovarian and cervical
      cancer in monotherapy and in combination. METHODS: This article reviews the
      mechanism of action, pharmacokinetics, toxicity and efficacy of topotecan. The
      paper also reports the principal phases II and III studies of topotecan in
      advanced or recurrent ovarian and cervical cancer. RESULTS: Topotecan (Hycamtin),
      currently indicated for the treatment of relapsed ovarian cancer, has
      demonstrated activity both in platinum-sensitive and in platinum-resistant
      disease. The combination cisplatin-topotecan for the treatment of advanced and
      recurrent cervical cancer has demonstrated a clinical benefit in terms of
      response rate, overall survival and progression free survival. Haematological
      toxicity of topotecan also is easy to manage and not cumulative, especially with
      the weekly scheduled recently introduced in clinical practice. CONCLUSION:
      Topotecan (Hycamtin) will continue to play a role in the treatment of advanced
      ovarian and cervical cancer, in monotherapy or in combination with other
      cytotoxic agents.

PMID- 19766513
TI  - Human blood mononuclear cell in vitro cytokine response before and after two
      different strenuous exercise bouts in the presence of bloodroot and Echinacea
      extracts.
AB  - The purpose of this multidisciplinary investigation was to characterize cytokine
      production by human blood mononuclear cells after 2 contrasting exercise bouts (a
      maximal graded oxygen consumption [VO(2)max] test and 90 min of cycling at 85% of
      ventilatory threshold [VT]) when stimulated in vitro with extracts from bloodroot
      (Sanguinaria canadensis), coneflower (Echinacea tennesseensis), or solvent
      vehicle controls. Blood was sampled pre- and post-exercise. Production of TNF, IL
      1beta, and IL-10 were measured at 24, 48, and 72 h, respectively. In the VO(2)max
      test there was a main effect of exercise such that exercise increased cytokine
      synthesis and a main effect of stimulant such that bloodroot extracts
      significantly increased cytokine production compared to other stimulants or
      controls. In the 90-min bout, there was a main effect of exercise for TNF and IL
      1beta (but not IL-10) such that exercise decreased cytokine synthesis and a main
      effect of stimulant such that bloodroot extracts significantly increased cytokine
      production compared to other stimulants or controls, with exercisexstimulant
      interactions for both IL-1beta and IL-10. A similar though weaker effect was seen
      with Echinacea extracts; subsequent biochemical analyses suggested this was
      related to alkamide decay during 3 years undisturbed storage at ultralow (-80
      degrees C) temperature. In this study, the VO(2)max test was associated with
      enhanced cytokine production whereas the 90-min cycling at 85% VT was associated
      with suppressed cytokine production. Bloodroot extracts were able to increase
      cytokine production in both contexts. Herbal extracts purported to offset
      exercise-associated effects on immune activity warrant continued investigation.

PMID- 19766514
TI  - Cardiopulmonary effects of dorsal recumbency and high-volume caudal epidural
      anaesthesia with lidocaine or xylazine in calves.
AB  - The objective of this study was to investigate the cardiopulmonary effects of
      dorsal recumbency and high-volume caudal epidural anaesthesia induced by xylazine
      or lidocaine in calves. Twenty-eight German Holstein-Friesian calves (57.7 +/-
      5.8 kg bodyweight) were randomly allocated to four equal (n=7) groups for one of
      the following treatments, each injected into the caudal epidural space: (1) no
      treatment (control); (2) sterile saline (0.4 mL/kg); (3) lidocaine (2%), or (4)
      xylazine (0.1mg/kg), with the latter two treatments diluted with sterile saline
      to a final volume of 0.4 mL/kg. Cardiac output was measured by thermodilution and
      cardiopulmonary function parameters were determined at preset time intervals over
      an observation period of 335 min. After baseline measurements in the standing
      animals, the calves received the epidural injection and were positioned in dorsal
      recumbency for 95 min. In the control group, dorsal recumbency caused a
      significant (P < 0.05) decrease in cardiac index (CI) (baseline 210 +/- 12
      mL/kg/min, minimum value 174 +/- 11 mL/kg/min), without significant change in
      blood-gas values. Calves treated with lidocaine or saline did not differ from the
      control group in any of the parameters measured. The epidural injection of
      xylazine caused a more pronounced decrease in CI (baseline 209 +/- 12 mL/kg/min,
      minimum value 127 +/- 11 mL/kg/min), compared to the control group. At the same
      time, the heart rate was significantly (P < 0.05) decreased (baseline 113 +/- 7
      beats per min, minimum value 86 +/- 4 beats per min). Furthermore, a significant
      (P < 0.05) increase in the oxygen extraction ratio was observed in the xylazine
      group (baseline 39 +/- 7%, maximum value 47 +/- 7%). In all groups,
      cardiorespiratory parameters remained within physiological limits. Changes in
      cardiopulmonary function induced by dorsal recumbency and high-volume caudal
      epidural anaesthesia with lidocaine or xylazine were well tolerated in healthy
      calves.

PMID- 19766515
TI  - Molecular docking of a series of peptidomimetics in the trypanothione binding
      site of T. cruzi trypanothione reductase.
AB  - Chagas' disease (CD) has been responsible for many deaths and disabilities mainly
      in South America. Currently, 40 million people are at risk of acquiring this
      disease and, existing therapies are still unsatisfactory, presenting harsh side
      effects. Therefore, the development of new chemical entities to reverse this
      state is critical. A series of peptidomimetics, developed by Mc Kie et al. (2001)
      [11], showed a reversible and competitive inhibition against Trypanosoma cruzi
      Trypanothione Reductase (TR). These inhibitors may be used as basis of lead
      compounds in the design of new drug candidates for the treatment of CD. In this
      work, we have docked this series of peptidomimetics into the TR binding site,
      using the FlexX algorithm as implemented in the Sybyl program, in order to access
      the binding mode of this class of compounds in the target enzyme.

PMID- 19766516
TI  - Cerebral folate deficiency and CNS inflammatory markers in Alpers disease.
AB  - We describe a 3.5-year-old female with Alpers disease with a POLG genotype of
      p.A467T/p.G848S and with a lethal outcome. Laboratory investigation revealed
      elevated CSF neopterin, IL-6, IL-8, IFN-gamma, reduced CSF 5
      methyltetrahydrofolate (5MTHF), and increased serum as well as CSF folate
      receptor blocking autoantibodies. Treatment with oral Leucovorine (5-formyl
      tetrahydrofolate) was initiated at 0.25mg/kg bid, and later increased to 4mg/kg
      bid. Under treatment CSF levels of 5MTHF, seizure frequency and communicative
      abilities improved. Over a time span of 17months, CSF levels of IL-6 and IFN
      gamma decreased, levels of folate receptor blocking autoantibodies continued to
      raise, whereas CSF IL-8 remained elevated 1500-fold above normal. The child died
      without apparent stress at the age of 5.5years. Alpers disease, a
      neurodegenerative disease usually presents in the first years of life as a
      progressive encephalopathy with multifocal myoclonic seizures, developmental
      regression, cortical blindness and early death. The underlying genetic defect has
      been attributed to mutations of the catalytic subunit of the mitochondrial DNA
      polymerase-gamma leading to an organ-specific mitochondrial DNA depletion
      syndrome with reduced activity of respiratory chain enzyme complexes in the brain
      and the liver. A curative therapy is not available. This case report of Alpers
      disease provides new insights into the pathophysiology of Alpers disease, where
      mitochondrial dysfunction in conjunction with inflammatory cytokines and blocking
      folate receptor autoantibodies may lead to a secondary cerebral folate deficiency
      syndrome. The treatment of the latter provides relief to the patient without
      stopping the underlying disease.

PMID- 19766517
TI  - Prevalence of tinea pedis, tinea unguium of toenails and tinea capitis in school
      children from Barcelona.
AB  - OBJECTIVE: To evaluate the prevalence of tinea capitis, tinea pedis, and tinea
      unguium in children from several schools of Barcelona city. METHODS: During the
      period of 2003-2004, a prospective cross-sectional study was carried out in 1,305
      children (9% immigrant population) between the ages 3 and 15 in 17 schools in
      Barcelona. A systematic examination of the feet, (including nails and scalp), was
      performed to identify lesions compatible with tinea. Cultures of scalp and feet
      samples were done and analysis of environmental samples was performed for
      dermatophyte isolation. RESULTS: Dermatophytes were isolated in 2.9% of the
      samples with a prevalence of 2.5% in feet, 0.23% in scalp, and 0.15% in nails of
      the feet. The predominant etiologic agents in feet were Trichophyton
      mentagrophytes in 45.7% of the cases and Trichophyton rubrum in 31.4%. In the
      nails, T. rubrum and Trichophyton tonsurans were isolated, while T.
      mentagrophytes (2 cases) and Trichophyton violaceum (1 case) were identified in
      scalp samples. Forty-five per cent of dermatophytes were isolated from healthy
      feet, the majority of cases in children 13- 15-years-old (p < 0.05). Microsporum
      gypseum was the only agent identified in the environmental samples, and was also
      found in one of the cases of tinea pedis. CONCLUSION: The results of this study
      demonstrate a low prevalence of tinea capitis and tinea unguium in school
      children of Barcelona. On the contrary, high prevalence of dermatophytes in feet
      was found. It highlights the high prevalence of healthy carriers of dermatophytes
      in feet.

PMID- 19766518
TI  - Mycobiota and mycotoxins in fermented feed, wheat grains and corn grains in
      Southeastern Buenos Aires Province, Argentina.
AB  - Wheat (as bran) and corn (as dry grain or fermented feed) are main ingredients of
      feedstuffs used in local cattle and pig farms in the South of the Buenos Aires
      Province (Argentina). Therefore, determining mycobiota and mycotoxins in wheat
      and corn is of prime importance for developing feed management techniques to
      optimise animal production and to minimize toxicity. Then, a mycological survey
      was carried out in the Southeastern part of the Buenos Aires Province, in order
      to identify the mycobiota and the main mycotoxins present in fermented feed,
      wheat grain and corn grain samples. Samples were cultured for fungal
      quantification, isolation and identification, and analysed for deoxynivalenol
      (DON), zearalenone (ZEA), T-2 toxin and aflatoxins (AFLA). Penicillium (74%),
      Aspergillus (32%) and Scopulariopsis (21%) were the prevalent genera in fermented
      feed. Penicillium (70%), Fusarium (47%) and Aspergillus (34%) were the most
      frequent fungi isolated from corn. Penicillium (42%), Fusarium (27%) and
      Alternaria (25%) were the most frequently recovered genera from wheat. DON was
      detected in 59% of the corn samples, in 45% of the wheat samples and in 38% of
      the silage samples. ZEA was detected in 36% of the corn samples, in 49% of the
      wheat samples and in 16% of the silage samples. T-2 toxin and aflatoxin B1 were
      each detected in 4% of the corn samples. Eighteen percent of the fermented feed
      samples showed T-2 contamination. Fermented feed and wheat samples were negative
      for AFLA.

PMID- 19766519
TI  - [Quality of life analysis in patients with an implantable cardioverter
      defibrillator].
AB  - OBJECTIVES: To describe possible changes in the quality of life (QL) and to
      identify possible differences associated to sociodemographic and clinical
      variables after being given an implantable cardioverter-defibrillator (ICD).
      METHOD: Descriptive cross-sectional study, selecting 241 consecutive patients for
      a subcutaneous or subpectoral ICD implantation. One-hundred and fifty-seven
      patients met inclusion criteria. Introduction letter along with the assessment
      tool was mailed to them. Assessment tool used was the Euroqol-5D (EQ5D),
      validated and translated for a Spanish population. EQ5D describes health status
      in 5 domains: mobility (MO), self-care (SC), usual activity (UA), pain/discomfort
      (PD) and anxiety/depression (AD). It included a visual analogue scale (VAS) where
      the endpoints are labelled 'Best imaginable health state' and 'Worst imaginable
      health state'; one before and another after ICD implantation. RESULTS: Ninety
      valid assessments were received: 80 males, mean age 61.2+/-13.1 years. Patients
      with EQ5D problems: MO 25 (27.7%), SC 8 (8.8%), UA 32 (35.5%), PD 22 (24.4%) and
      AD 29 (32.2%). Patients with ICD discharges had a higher percentage of problems
      in all EQ5D domains, being significant in PD and AD. Fifty four patients (60%)
      experienced a significant improvement in QL after ICD implant using the visual
      analogue scale score (75 points after vs. 50 points before; P<0.001).
      CONCLUSIONS: The majority of ICD patients gain QL after implantation, but this
      gain is more limited in younger patients and those who have received discharges.

PMID- 19766520
TI  - [A qualitative examination of inappropriate hospital admissions and lengths of
      stay].

PMID- 19766521
TI  - [Coping with occupational stress among nursing staff by participatory action
      research].
AB  - OBJECTIVE: To describe a collaborative practice focused on coping with the
      occupational stress among nursing staff in a hospital setting. METHOD: These
      practices focus on the contextualization of the problems and the design and
      implementation of actions using the psychopolitical model and the participatory
      action research (PAR) methodology. Participants were the nurses of 4 units of
      internal medicine at the public hospital "Virgen Macarena" in Seville. We have
      used the ISTAS questionnaire, interviews and discussion groups through which
      nurses and researchers have assessed, defined, proposed and implemented different
      actions in order to improve their work conditions. RESULTS: Problematic
      situations detected by the questionnaires are associated to psychological
      demands, role conflicts and esteem. The main cause of stress in healthcare
      professionals is the lack of staff, according to the opinion laid by supervisors.
      In the discussion groups, nurses accorded to get involved in three situations: a)
      the need of the continuous presence of an orderly to move patients which aren't
      autonomous; b) the need of controlling visit hours and the number of accompanying
      people with each patient; and c) the need to improve the registration of the
      activities assigned to nursing staff. CONCLUSIONS: Among the strength of the
      psychopolitical model and PAR in a hospital context we must emphasize on the
      mobilization of professionals and the development of a critical consciousness.
      Among the weakness, those derived from bureaucratic processes. These barriers
      imply a challenge for change and organizational development.

PMID- 19766522
TI  - [Occupational nursing. Always a specialty. A future option].

PMID- 19766523
TI  - [Potential place of FDG-PET for the GTV delineation in head and neck and lung
      cancers].
AB  - The recent progresses performed in imaging, computational and technological
      fields bring new opportunities to achieve high precision radiation dose delivery.
      However, IMRT requires a particular attention at the target delineation step to
      avoid inadequate dosage to TVs/OARs. In this context, the biological information
      provided by PET might advantageously complete CT-Scan to refine the target
      delineation in HNSCC and lung cancer. Integrating PET into the treatment planning
      however requires the use and validation of accurate and reproducible segmentation
      methods, which adequately integrate the PET image properties such as the blur
      effect and the high level of noise. In this context, we developed specific tools,
      i.e. edge-preserving filters for denoising and deconvolution algorithms for
      deblurring that allowed the detection of gradient intensity peaks. Our gradient
      based method has been validated on phantom and patient materials, and proved to
      be more accurate than threshold-based approaches. With this tool in hand, we
      demonstrated that the use of FDG-PET resulted in smaller TVs than the CT-based
      TVs, on both pre- and per-treatment images, and significantly improved the dose
      distributions to the TVs/OARs. This opens avenues for dose escalation strategies
      that might potentially improve the tumor local control.

PMID- 19766524
TI  - [Breast cancer irradiation in elderly].
AB  - In Western countries, about 25% of breast cancers (BC) occur in women older than
      70 years old. Local control is a crucial step to cure disease, because
      locoregional relapse (LRR) is a major risk factor of subsequent metastases. After
      mastectomy, radiotherapy (RT) confirmed a very high value (regardless of age) in
      several trials and meta-analyses, especially in case of high LRR risk factors
      (i.e. axillary nodal involvement). Globally, RT reduces LRR rates by 60-70% and
      also increases long-term survival rates by 8-9%. After breast conserving surgery,
      several trials and meta-analyses confirmed that RT decreases 10-year local
      recurrence rates from 20-25 to 5-8%. RT replacement by hormonal treatment leads
      to a significantly higher LRR rate. Hypofractionated RT schemes could usefully
      apply to elderly people, but partial breast irradiation techniques are still
      under investigation. Finally, all elderly fitted women should receive adjuvant RT
      according to general guidelines with optimal technique in order to avoid
      cardiotoxicity. Indeed, under-treatment has an unfavourable effect on long-term
      survival.

PMID- 19766525
TI  - [Proton magnetic resonance spectroscopic imaging and other types of metabolic
      imaging for radiotherapy planning in adult and pediatric high-grade gliomas].
AB  - Radiation therapy improves survival in high-grade gliomas but most patients
      relapse and usually within radiation fields. This may be due to uncertainties in
      target delineation and difficulties in identifying radioresistant regions for
      dose escalation. The use of T1 and T2-weighted magnetic resonance imaging (MRI)
      coregistration on the planning CT improves the target volume definition but
      magnetic resonance spectroscopic imaging (MRSI) and other types of metabolic and
      functional imaging (perfusion MRI, diffusion-weighted MRI, positron emission
      tomography (PET) imaging) may give useful additional information for target
      delineation. This article focuses on the potential of each imaging modality:
      assessment of response to treatment, detection of abnormalities not seen on MRI,
      predictive value for the site of local relapse. The incorporation of such
      techniques may improve target volume definition.

PMID- 19766526
TI  - [Help for delineation: what kind of tools?].
AB  - The planning of radiotherapy has known major developments during the last years.
      With the emergence of news techniques such as conformational radiotherapy,
      intensity modulated radiation therapy or stereotactic radiation therapy, the
      definition of target volumes was of great importance. The recommendations for the
      target volumes definition have been defined in the ICRU 50 and 62 reports,
      without any guidelines for volume delineation. Among the uncertainties that may
      influence the outcome after irradiation, the intra- and interobservers variations
      in delineation are the most important. Many teams have offered guidelines or
      atlases to homogenize these volumes and reduce these variations related to
      medical intervention. The aim of this paper is to present the main
      recommendations.

PMID- 19766527
TI  - [Improving healthcare: safety lessons from anesthesia, prospects for
      perinatology?].
AB  - This review examines current research on healthcare safety in highly dynamic
      domains of anesthesia and surgery. It emphasizes how checklists implementation
      and training program based on CRM and simulation may significantly improve
      interprofessional teamwork in a multidisciplinary obstetrical setting.

PMID- 19766528
TI  - Enzymatic transglycosylation for glycoconjugate synthesis.
AB  - Remarkable advances have been made in recent years in exploiting the
      transglycosylation activity of glycosidases and glycosynthase mutants for
      oligosaccharide and glycoconjugate synthesis. New glycosynthases were generated
      from retaining glycosidases, inverting glycosidases, and those that proceed in a
      mechanism of substrate-assisted catalysis. Directed evolution coupled with
      elegant screening methods has led to the discovery of an expanding number of
      glycosynthase mutants that show improved catalytic activity and/or altered
      substrate specificity. In particular, enzymatic transglycosylation strategy has
      been recently extended to the synthesis of complex glycoconjugates, including
      glycosphingolipids, N-glycoproteins, and other glycosylated natural products.

PMID- 19766529
TI  - Nonlinear fluorescence quenching of newly synthesized coumarin derivative by
      aniline in binary mixtures.
AB  - The fluorescence quenching of newly synthesized coumarin (chromen-2-one)
      derivative, 4-(5-methyl-3-phenyl-benzofuran-2-yl)-6-chloro-chromen-2-one (MPBClC)
      by aniline in different binary solvent mixtures of benzene and acetonitrile have
      been reported by steady state fluorescence measurements. All the measurements
      were carried out at room temperature (296K). A positive curvature from linearity
      was observed in the Stern-Volmer (S-V) plot in all the solvent mixtures. Various
      rate parameters for the fluorescence quenching have been determined by sphere of
      action static quenching model and finite sink approximation model. The results
      show that the positive curvature in the S-V plot is due to both static and
      dynamic quenching processes. Further, with the use of finite sink approximation
      model, it is concluded that these bimolecular reactions are diffusion-limited.

PMID- 19766530
TI  - Differentiation and quality estimation of Cordyceps with infrared spectroscopy.
AB  - Heretofore, a scientific and systemic method for differentiation and quality
      estimation of a well-known Chinese traditional medicine, 'Cordyceps', has not
      been established in modern market. In this paper, Fourier-transform infrared
      spectroscopy (FTIR) and two-dimensional correlation infrared spectroscopy (2D-IR)
      are employed to propose a method for analysis of Cordyceps. It has presented that
      IR spectra of real Cordyceps of different origins and counterfeits have their own
      macroscopic fingerprints, with discriminated shapes, positions and intensities.
      Their secondary derivative spectra can amplify the differences and confirm the
      potentially characteristic IR absorption bands 1400-1700cm(-1) to be investigated
      in 2D-IR. Many characteristic fingerprints are discovered in 2D-IR spectra in the
      range of 1400-1700cm(-1) and hetero 2D spectra of 670-780cm(-1)x1400-1700cm(-1).
      The different fingerprints display different chemical constitutes. Through the
      three steps, different Cordyceps and their counterfeits can be discriminated
      effectively and their qualities distinctly display. Successful analysis of eight
      Cordyceps capsule products has proved the practicability of the method, which can
      also be applied to the quality estimation of other Chinese traditional medicines.

PMID- 19766531
TI  - Iron speciation in natural hyperacid water investigated by Mossbauer
      spectroscopy.
AB  - We have demonstrated the usefulness of the archetypical solid state-technique of
      Mossbauer spectroscopy to non-invasive studies of the redox and coordination
      chemistry of iron in a natural hyperacid solution from Iron Mountain, CA.
      Suitable fast cooling conditions were used to prepare a glass from the natural
      solution. Measurements of spectra at low temperatures (6 and 15K) and in large
      external magnetic fields (6T) of the glassy, frozen solution revealed a behaviour
      characteristic of slow paramagnetic relaxation of ferric ions. Analyses of the
      spectral components are in good agreement with dominance of hexaaquairon(III)
      ions.

PMID- 19766532
TI  - Millennium Global Village-Net: bringing together Millennium Villages throughout
      sub-Saharan Africa.
AB  - The Millennium Villages Project (MVP), based at The Earth Institute at Columbia
      University, is a bottom-up, community led approach to show how villages in
      developing countries can get out of the poverty trap that afflicts more than a
      billion people worldwide. With well-targeted, practical inputs can help the
      community invest in a path leading to self-sustaining development. There are 80
      Millennium Villages clustered in 10 countries throughout sub-Saharan Africa. MVP
      is an important development process for empowering communities to invest in a
      package of integrated interventions aiming to increase food production, improve
      access to safe water, health care, education and infrastructure. The process
      benefits from synergies of the integrated approach and relies on community
      leadership as empowered by proven technological inputs. MVP is committed to a
      science-based approach to assess and monitor the progress of the communities
      towards clear objectives; the Millennium Development Goals (MDGs) and to do so
      with mechanisms that are scalable and sustainable. This approach offers much more
      than simply collecting and analyzing data since the mechanism used for recording
      progress would provide a bridge over the divide which separates the haves and the
      have-nots (by facilitating the sharing of solutions from one community to another
      bidirectionally). By so doing, it allows people to enhance their own futures in a
      sustainable manner. Solutions found in one community are transferable to similar
      communities in other MVP villages. To achieve this goal, the MVP requires an
      information and communication system which can provide both necessary
      infrastructure for monitoring and evaluation, and tools for communicating among
      the villages, cities and countries. This system is called the Millennium Global
      Village-Net (MGV-Net). It takes advantage of the latest in open source software
      (OpenMRS), databases (MySQL), interface terminology, a centralized concept
      dictionary, and uses appropriate technology locally for data entry.

PMID- 19766533
TI  - Group C rotavirus, detection in Southeastern Brazil after 15 years.

PMID- 19766534
TI  - Neurodevelopmental outcomes following ganciclovir therapy in symptomatic
      congenital cytomegalovirus infections involving the central nervous system.
AB  - BACKGROUND: Ganciclovir protects against hearing deterioration in infants with
      symptomatic congenital cytomegalovirus (CMV) disease involving the central
      nervous system (CNS). OBJECTIVES: To assess the neurodevelopmental impact of
      ganciclovir therapy in this population. STUDY DESIGN: 100 neonates were enrolled
      into a controlled Phase III study of symptomatic congenital CMV involving the
      CNS, and were randomized to either 6 weeks of intravenous ganciclovir or no
      treatment. Denver developmental tests were performed at 6 weeks, 6 months, and 12
      months. For each age, developmental milestones that > or =90% of normal children
      would be expected to have achieved were identified. The numbers of milestones not
      met ("delays") were determined for each subject. The average number of delays per
      subject was compared for each treatment group. RESULTS: At 6 months, the average
      number of delays was 4.46 and 7.51, respectively, for ganciclovir recipients and
      "no treatment" subjects (p=0.02). At 12 months, the average number of delays was
      10.06 and 17.14, respectively (p=0.007). In a multivariate regression model, the
      effect of ganciclovir therapy remained statistically significant at 12 months
      (p=0.007). CONCLUSIONS: Infants with symptomatic congenital CMV involving the CNS
      receiving intravenous ganciclovir therapy have fewer developmental delays at 6
      and 12 months compared with untreated infants. Based on these data as well as the
      previously published data regarding ganciclovir treatment and hearing outcomes, 6
      weeks of intravenous ganciclovir therapy can be considered in the management of
      babies with symptomatic congenital CMV disease involving the CNS. If treatment is
      initiated, it should be started within the first month of life and patients
      should be monitored closely for toxicity, especially neutropenia. Since existing
      data only address the treatment of symptomatic congenital CMV disease involving
      the CNS, these data cannot be extrapolated to neonates with other manifestations
      of CMV disease, including asymptomatic babies and symptomatic babies who do not
      have CNS involvement.

PMID- 19766535
TI  - Mechanisms controlling motor output to a transfer hand after learning a
      sequential pinch force skill with the opposite hand.
AB  - OBJECTIVE: Training to perform a serial reaction-time task (procedural motor
      learning) with one hand results in performance improvements in the untrained as
      well as in the trained hand, a phenomenon referred to as intermanual transfer.
      The aim of this study was to investigate the neurophysiological changes
      associated with intermanual transfer associated with learning to perform an
      eminently different task involving fine force control within the primary motor
      cortex (M1). We hypothesized that intermanual transfer of learning such a task
      would reveal intracortical changes within M1. METHODS: Speed (time to complete
      each sequence) and accuracy (% of accuracy errors) of motor performance were
      measured in both hands before and after right (dominant) hand practice.
      Transcranial magnetic stimulation (TMS) was used to characterize recruitment
      curves (RC), short intracortical inhibition (SICI), intracortical facilitation
      (ICF) and interhemispheric inhibition (IHI) from the left to the right M1.
      RESULTS: Practice resulted in significant improvements in both speed and accuracy
      in the right trained hand and in the left untrained hand. RC increased in the
      left M1, SICI decreased in both M1s, and IHI from the left to the right M1
      decreased. No changes were identified in ICF nor in RC in the right M1.
      CONCLUSIONS: Our results suggest that some neurophysiological mechanisms
      operating in the M1 controlling performance of an untrained hand may contribute
      to optimize the procedure for selecting and implementing correct pinch force
      levels. SIGNIFICANCE: These results raise the hypothesis of a contribution of
      modulation of SICI and IHI, or an interaction between both to intermanual
      transfer after learning a sequential pinch force task.

PMID- 19766536
TI  - Key pathogens and emerging therapies in infectious diseases.

PMID- 19766537
TI  - Esterases and autoimmunity: the sialic acid acetylesterase pathway and the
      regulation of peripheral B cell tolerance.
AB  - The best studied mechanisms of B cell tolerance are receptor editing, clonal
      deletion and anergy. All of these mechanisms of B cell tolerance depend on the
      induction of signaling downstream of the B cell receptor by self-antigens.
      Another important and distinct mechanism of B cell tolerance involves the
      repression of antigen receptor signaling rather than its induction, utilizes the
      Lyn Src-family kinase, the SHP-1 tyrosine phosphatase, inhibitory members of the
      Siglec family, and a carbohydrate-modifying enzyme that is capable of negatively
      regulating B cell receptor activation known as sialic acid acetylesterase.

PMID- 19766538
TI  - Forced expression of suppressor of cytokine signaling 3 in T cells protects the
      development of concanavalin A-induced hepatitis in mice.
AB  - T cells play central roles in liver diseases, but the regulatory mechanism by
      cytokine signaling is not well understood. In the present study, we explored the
      role of SOCS3 in T cells in concanavalin A (ConA)-induced hepatitis. Mice with T
      cell-specific overexpression of SOCS3 (SOCS3-cTg) showed reduced hepatic damage
      and improved mice survival relative to the control, an event that was associated
      with decreased apoptotic signals Fas and pStat1. Expression of Th1
      cytokines/chemokines was decreased in SOCS3-cTg liver with reduced expression of
      T-bet, a Th1-transcription factor. Flow cytometric analysis of the liver
      lymphocytes demonstrated that activated CD4(+) T cells, cytotoxic T cells and
      natural killer T cells were significantly decreased in SOCS3-cTg liver with
      decreased expression of perforin and granzyme B, injurious molecules for
      hepatocyte damage. These results suggest that forced expression of SOCS3 in T
      cells prevents ConA-induced liver injury by inhibiting several phases of Th1
      responses.

PMID- 19766539
TI  - Cortical kindling induces elevated levels of AMPA and GABA receptor subunit mRNA
      within the amygdala/piriform region and is associated with behavioral changes in
      the rat.
AB  - Cortical kindling causes alterations within the motor cortex and results in long
      standing motor deficits. Less attention has been directed to other regions that
      also participate in the epileptiform activity. We examined if cortical kindling
      could induce changes in excitatory and inhibitory receptor subunit mRNA in the
      amygdala/piriform regions and if such changes are associated with behavioral
      deficits. After cortical kindling, amygdala/piriform regions were dissected to
      analyze mRNA levels of NMDA, AMPA, and GABA receptor subunits using reverse
      transcription polymerase chain reaction, or rats were subjected to a series of
      behavioral tests. Kindled rats had significantly greater amounts of GluR1 and
      GluR2 AMPA receptor mRNA, and alpha1 and alpha2 GABA receptor subunit mRNA,
      compared with sham controls, which was associated with greater anxiety-like
      behaviors in the elevated plus maze and reduced freezing behaviors in the fear
      conditioning task. In summary, cortical kindling produces dynamic receptor
      subunit changes in regions in addition to the seizure focus.

PMID- 19766540
TI  - Haptoglobin phenotype and apolipoprotein E polymorphism: relationship to
      posttraumatic seizures and neuropsychological functioning after traumatic brain
      injury.
AB  - The relationship of genetic predisposition to reduced iron capacity and
      apolipoprotein E (APOE) to posttraumatic seizures (PTSs) and neuropsychological
      outcomes was investigated in patients with traumatic brain injuries from a prior
      valproate clinical study. Haptoglobin concentration/phenotype and APOE genotype
      were determined in 25 patients with PTSs and 26 control (no PTSs) subjects
      approximately 10 years after traumatic brain injury. Haptoglobin phenotype was
      also determined in previously collected frozen samples for 25 additional patients
      with PTSs and 32 no-PTS subjects. There was no relationship between haptoglobin
      phenotype or APOE genotype and occurrence of PTSs. APOE genotype was not related
      to neuropsychological outcome; however, when adjustments were made for
      differences in educational levels, APOE epsilon4 subjects did worse, especially
      on tests of verbal intellectual and verbal memory skills. In contrast to our
      hypothesis, those with haptoglobin 1-1 (high-affinity binder of hemoglobin)
      scored somewhat worse on Verbal IQ and Tapping D at 1 and 12 months after injury.

PMID- 19766541
TI  - Amygdala volumes in childhood absence epilepsy.
AB  - Abnormal amygdala volumes in pediatric mood-anxiety disorders and attention
      deficit hyperactivity disorder (ADHD), as well as high rates of these diagnoses
      in childhood absence epilepsy (CAE), prompted this study of amygdala volume in
      CAE. Twenty-six children with CAE and 23 normal children, aged 6.6-15.8 years,
      underwent MRI at 1.5 T. The tissue imaged with MRI was segmented, and amygdala
      volumes were obtained by manual tracings. There were no significant amygdala
      volume differences between the CAE and normal groups. Within the CAE group,
      however, the children with ADHD had significantly smaller amygdala volumes than
      the subjects with CAE with no psychopathology and those with mood/anxiety
      diagnoses. There was also a significant relationship between higher seizure
      frequency and greater amygdala asymmetry in the epilepsy group. Given ongoing
      development of the amygdala during late childhood and adolescence, despite the
      lack of significant group differences in amygdala volumes, the association of
      amygdala volume abnormalities with ADHD and seizure frequency implies a possible
      impact of the disorder on amygdala development and CAE-associated comorbidities,
      such as ADHD.

PMID- 19766542
TI  - The FAS gene, brain volume, and disease progression in Alzheimer's disease.
AB  - OBJECTIVE: We sought to identify single-nucleotide polymorphisms (SNPs)
      associated with Alzheimer's disease (AD) progression and brain volume. METHODS:
      Ninety-seven SNPs were genotyped in 243 subjects from a longitudinal study of
      healthy aging. Subjects who received a diagnosis of cognitive impairment (CI) at
      any study visit (before their most recent visit) and had DNA in the study's DNA
      bank were included. Progression of AD was defined as the duration from onset of
      CI to diagnosis of AD. Association of each of the 97 SNPs with AD progression was
      tested via Cox model. Those SNPs meeting a criterion of nominal significance (P <
      0.05) for association with AD progression were reassessed to account for multiple
      testing by repeating the marker selection process in 10,000 random permutations.
      Next, the association between the one SNP that survived the multiple-testing
      adjustment and brain volume was determined by multiple regression analysis in a
      subgroup of subjects for whom magnetic-resonance imaging (MRI)-derived brain
      volume data were available. Brain volumes were adjusted for age at MRI, gender,
      and time from MRI to onset of CI. RESULTS: The minor allele of rs1468063 in the
      FAS gene, which is member 6 of the tumor necrosis factor receptor superfamily,
      was significantly associated with faster AD progression after adjustment for
      multiple testing (P(permutation) = 0.049). The same allele in rs1468063 was
      associated with smaller brain volumes and larger ventricular volumes (P = 0.02
      and 0.04, respectively). CONCLUSIONS: The FAS gene, which plays a role in
      apoptosis, may be associated with AD by modulating the apoptosis and neuronal
      loss secondary to AD neuropathology.

PMID- 19766543
TI  - Heart rate variability of young men with idiopathic hypogonadotropic
      hypogonadism.
AB  - BACKGROUND: There is little data available regarding the effects of male sex
      hormones on cardiac autonomic function. The aim of this study is to evaluate the
      association between hormones of male hypothalamo-pitiutary-gonadal axis and
      cardiac autonomic function by comparing heart rate variability (HRV) parameters
      of young male idiopathic hypogonadotropic hypogonadism patients with those of
      healthy controls. METHODS: The study consisted of 22 male idiopathic
      hypogonadotropic hypogonadism patients (mean age 20.8+/-1.2years) and the same
      number of age-matched healthy male controls (mean age 21.0+/-1.5years). A 24-hour
      Holter monitoring was performed to assess the time and frequency-domain
      parameters. The HRV parameters of patients and control groups were compared, and
      possible associations between levels of tested hormones and HRV parameters were
      evaluated. RESULTS: The standard deviation of all NN intervals (SDNN), standard
      deviation of the averages of NN intervals in all 5min segments (SDANN), power in
      low frequency range (LF, ms(2)) and power in high frequency range (HF, ms(2))
      values of patients were significantly lower compared to those of controls
      (147.47+/-56.16 vs. 193.63+/-40.89; 138.31+/-57.64 vs. 190.15+/-43.94; 397.8+/
      236.7 vs. 491.5+/-208.4; and 133.6+/-97.4 vs. 198.5+/-91.6 respectively; p<0.05
      for all). Significant negative correlations were observed between serum FSH, LH
      and testosterone levels and most of the HRV parameters. CONCLUSIONS: Deficiency
      in the male hypothalamo-pituitary-gonadal axis seems to adversely affect cardiac
      autonomic modulation with increased sympathetic and decreased parasympathetic
      components of HRV.

PMID- 19766544
TI  - Polynuclear palladium complexes with biogenic polyamines: AFM and voltammetric
      characterization.
AB  - Polynuclear Pd(II) complexes with biogenic polyamines present great potential
      clinical importance, due to their antiproliferative and cytotoxic activity
      coupled to less severe side-effects. The adsorption process and the redox
      behaviour of two polynuclear palladium chelates with spermine (Spm) and
      spermidine (Spd), Pd(II)-Spm and Pd(II)-Spd, as well as of their ligands Spm and
      Spd, were studied using atomic force microscopy (AFM) and voltammetry at highly
      oriented pyrolytic graphite and glassy carbon electrodes. AFM revealed different
      adsorption patterns and degree of surface coverage, correlated with the chelate
      structure, concentration of the solution, applied potential and voltammetric
      behaviour of the Spm, Spd, Pd(II)-Spm and Pd(II)-Spd systems. The voltammetric
      study of Spm and Spd showed that these biogenic polyamines undergo an
      irreversible and pH-dependent oxidation. In acid medium the polyamines are fully
      protonated, rendering their oxidation more difficult. With increasing pH the
      oxidation potential for both Spm and Spd is shifted to less positive values,
      indicating a greater ease of oxidation in alkaline medium. The Pd(II)-Spm and
      Pd(II)-Spd complexes dissociate at high negative or high positive potentials. The
      application of a positive potential induced the oxidation of these Pd complexes
      and the formation of mixed layers of palladium oxides, Spm/Spd and Pd(II)
      Spm/Pd(II)-Spd.

PMID- 19766545
TI  - Microfluidic, bead-based assay: Theory and experiments.
AB  - Microbeads are frequently used as a solid support for biomolecules such as
      proteins and nucleic acids in heterogeneous microfluidic assays. However,
      relatively few studies investigate the binding kinetics on modified bead surfaces
      in a microfluidics context. In this study, a customized hot embossing technique
      is used to stamp microwells in a thin plastic substrate where streptavidin-coated
      agarose beads are selectively placed and subsequently immobilized within a
      conduit. Biotinylated quantum dots are used as a label to monitor target analyte
      binding to the bead's surface. Three-dimensional finite element simulations are
      carried out to model the binding kinetics on the bead's surface. The model
      accounts for surface exclusion effects resulting from a single quantum dot
      occluding multiple receptor sites. The theoretical predictions are compared and
      favorably agree with experimental observations. The theoretical simulations
      provide a useful tool to predict how varying parameters affect microbead reaction
      kinetics and sensor performance. This study enhances our understanding of bead
      based microfluidic assays and provides a design tool for developers of point-of
      care, lab-on-chip devices for medical diagnosis, food and water quality
      inspection, and environmental monitoring.

PMID- 19766546
TI  - Portal vein thrombosis, revisited.
AB  - This review article aims to discuss the aetiology, pathophysiology, clinical
      presentation, diagnostic workup and management of portal vein thrombosis, either
      as a primary vascular liver disease in adults and children, or as a complication
      of liver cirrhosis. In addition, indications and limits of anticoagulant therapy
      are discussed in detail.

PMID- 19766547
TI  - Uptake and retention of 65Zn in lithium-treated rat liver: role of zinc.
AB  - AIM: To evaluate the effects of zinc on the biokinetics of (65)Zn in rat and its
      distribution in various organs and in subcellular compartment following lithium
      therapy. METHODS: Female wistar rats received either lithium treatment at a dose
      of 1.1g/kg in diet, zinc alone at a dose of 227 mg/L in drinking water, and
      combined lithium plus zinc for duration of four months. RESULTS: After four
      months of lithium treatment, liver enzymes increased significantly (glutamic
      oxaloacetic transaminase, +66.73%; glutamic pyruvic transaminase, +63.70%;
      alkaline phosphatase, +40.28%; p< or =0.001); zinc supplementation to lithium
      treated rats significantly reduced liver enzymes (glutamic oxaloacetic
      transaminase, -13.11%; glutamic pyruvic transaminase, -21.78%; alkaline
      phosphatase, -11.77%; p< or =0.001). The biological half-lives of (65)Zn showed
      an initial fast component (Tb(1)) and a slower component (Tb(2)). A significant
      increase in Tb(2) (38.82%, p< or =0.001) in liver was observed following lithium
      treatment, which significantly decreased following zinc treatment (21.71%, p< or
      =0.001). A significant decrease in the uptake of (65)Zn (53.93%, p< or =0.01) in
      liver was observed and in nuclear (p< or =0.01), mitochondrial (p< or =0.01), and
      microsomal (52.67%, p< or =0.001) fractions. A significant increase in the uptake
      of (65)Zn (82.92%, p< or =0.05) in liver microsomal fraction (34.09%, p< or
      =0.001) was observed in lithium-treated rats receiving zinc supplementation.
      CONCLUSION: The study suggests that zinc has the potential to regulate the
      biokinetics of (65)Zn and its subcellular distribution in rat liver following
      lithium therapy.

PMID- 19766548
TI  - Hepatic steatosis index: a simple screening tool reflecting nonalcoholic fatty
      liver disease.
AB  - BACKGROUND/AIMS: To optimize management of nonalcoholic fatty liver disease
      (NAFLD), a simple screening tool is necessary. In this study, we aimed to devise
      a simple index of NAFLD. STUDY: A cross-sectional study with 10,724 health check
      up subjects (5362 cases with NAFLD versus age- and sex-matched controls) was
      conducted. Study subjects were randomly assigned to a derivation cohort or a
      validation cohort. RESULTS: Multivariate analysis indicated that high serum
      alanine aminotransferase (ALT) to serum aspartate aminotransferase (AST) ratio,
      high body mass index (BMI), and diabetes mellitus were independent risk factors
      of NAFLD (all P<0.001). Using these variables, a formula was derived by a
      logistic regression model: hepatic steatosis index (HSI)= 8 x(ALT/AST ratio)+BMI
      (+2, if female; +2, if diabetes mellitus). HSI had an area under receiver
      operating curve of 0.812 (95% confidence interval, 0.801-0.824). At values of
      <30.0 or >36.0, HSI ruled out NAFLD with a sensitivity of 93.1%, or detected
      NAFLD with a specificity of 92.4%, respectively. Of 2692 subjects with HSI <30.0
      or >36.0 in the derivation cohort, 2305 (85.6%) were correctly classified. HSI
      was validated in the subsequent validation cohort. CONCLUSION: HSI is a simple,
      efficient screening tool for NAFLD that may be utilized for selecting individuals
      for liver ultrasonography and for determining the need for lifestyle
      modifications.

PMID- 19766549
TI  - [Moderate cerebral hypothermia in hypoxic-ischaemic encephalopathy: A new
      challenge in neonatal care].

PMID- 19766550
TI  - Long-term outcomes of bronchopulmonary dysplasia.
AB  - As more very preterm infants survive, more survivors will have bronchopulmonary
      dysplasia (BPD). Children with BPD have higher rates of cognitive, educational
      and behavioural impairments, and also reduced lung function, through childhood
      and into early life than would normally be expected. The importance of these
      neurological and respiratory problems later into adult life needs to be
      determined.

PMID- 19766551
TI  - Protecting microvascular anastomoses from desiccation during lengthy procedures.

PMID- 19766552
TI  - A prospective study in children: Pre- and post-surgery use of vitamin E in
      surgical incisions.
AB  - BACKGROUND: One of the main problems of elective surgery is the cosmetic result.
      OBJECTIVE: This prospective controlled study aims to determine the effects of
      topical vitamin E on cosmetic results in children. METHODS: A single-blind study
      was carried out. Topical vitamin E was used on the intended incision site for at
      least 15 days, thrice daily, before surgery and for at least 30 days, twice
      daily, after surgery (group A). The control group received topical petrolatum
      based ointment (group B). RESULTS: No patients in group A developed keloids. A
      total of 96% of patients (or parents) considered the cosmetic results very good.
      No patients had wound infection. In the control group, only 78% of patients (or
      parents) considered the cosmetic results very good and 13 (6.5%) patients
      developed keloids after 6 months. There were no cases of wound infection.
      CONCLUSION: Topical vitamin E before and after surgery improved surgical wound
      healing and improved cosmetic results.

PMID- 19766553
TI  - Negative pressure manoeuvre in microtia reconstruction with autologous rib
      cartilage.
AB  - In microtia reconstruction, maintaining a healthy contact between the skin and
      the fabricated cartilage framework is essential to attaining a smooth and
      accentuated contour of the reconstructed auricle. Conventional means to achieve
      this include bolster sutures and continuous suction drains, both of which have
      associated shortcomings. A new dressing method was developed and applied in 10
      consecutive patients who underwent the first of a two-stage microtia
      reconstruction using the Nagata technique. A small catheter was introduced into
      the space between the skin and the cartilage framework. Negative pressure was
      applied through the catheter, drawing the skin onto the cartilage framework. This
      evens out the skin, accentuates the contour of the framework and concurrently
      eliminates potential dead space. Skin contact on the framework is maintained
      whilst the catheter is removed and an occlusive transparent dressing is applied
      to the ear. Of the 10 cases in which this manoeuvre was performed, one had to be
      converted to the bolster suture technique due to a persistent air leak from the
      wound. Overall results of the nine cases in which this technique was carried out
      successfully demonstrate smooth skin contour and excellent definition of the
      fabricated framework. This negative pressure manoeuvre provides a simple, safe
      and consistent approach to achieving a smooth and accentuated contour in
      auricular reconstruction.

PMID- 19766554
TI  - New citizens for the life sciences.
AB  - For years, the general public have been helping scientists to track weather,
      count birds, and observe the universe. Now such citizen scientists are starting
      to tackle research projects in the life sciences. Laura Bonetta reports.

PMID- 19766555
TI  - Reprogramming to pluripotency: from frogs to stem cells.
AB  - This year's Albert Lasker Basic Medical Research Award goes to John Gurdon and
      Shinya Yamanaka for their contributions to our understanding of how to reprogram
      adult cells back to early embryonic states.

PMID- 19766556
TI  - Attacking cancer at its root.
AB  - This year the Lasker DeBakey Clinical Research Award will be shared by Brian
      Druker, Nicholas Lydon, and Charles Sawyers for their development of a targeted
      molecular therapy for treating chronic myeloid leukemia. Their work demonstrated
      the ability of drugs directed against cancer-causing oncogenes to turn a rapidly
      fatal malignancy into a manageable chronic disease.

PMID- 19766557
TI  - Structural ties between cholesterol transport and morphogen signaling.

PMID- 19766558
TI  - Transposon silencing by piRNAs.
AB  - In animal cells, small RNA molecules, called piRNAs, defend the genome against
      selfish DNA elements such as transposons. In this issue, Klattenhoff et al.
      (2009) report that an HP1 family protein, Rhino, is required for piRNA generation
      and transposon silencing in Drosophila germline cells. The results provide a link
      between heterochromatin and piRNA-mediated genome defense.

PMID- 19766559
TI  - p53: a new kingpin in the stem cell arena.
AB  - Identifying new regulators of the stem cell state offers potential for future
      gains in biomedicine. Evidence that the tumor suppressor p53 is a key regulator
      of the stem cell state (Cicalese et al., 2009) suggests a broad role for this
      protein and its pathways in the control of normal tissue homeostasis and tumor
      formation.

PMID- 19766560
TI  - Reducing the mystery of neuronal differentiation.
AB  - In the developing nervous system, neural progenitors exit the cell cycle and
      differentiate on a precise schedule, yet the mechanisms driving this process
      remain poorly defined. Yan et al. (2009) now identify a thiol-redox reaction
      mediated by the membrane protein GDE2 and the peroxiredoxin protein Prdx1 that
      promotes neurogenesis.

PMID- 19766561
TI  - A toggle switch in plant nitrate uptake.
AB  - In plants, the uptake of nitrate from the soil is a critical process controlled
      by complex regulatory networks that target nitrate transporters in the roots. In
      this issue, Ho et al. (2009) show that phosphorylation of the CHL1 nitrate
      transporter allows the plant root to sense and respond to different nitrate
      concentrations in the soil.

PMID- 19766562
TI  - Major evolutionary transitions in centromere complexity.
AB  - Centromeres are chromosomal elements that are both necessary and sufficient for
      chromosome segregation. However, the puzzlingly broad range in centromere
      complexity, from simple "point" centromeres to multi-megabase arrays of DNA
      satellites, has defied explanation. We posit that ancestral centromeres were
      epigenetically defined and that point centromeres, such as those of budding
      yeast, have derived from the partitioning elements of selfish plasmids. We
      further propose that the larger centromere sizes in plants and animals and the
      rapid evolution of their centromeric proteins is the result of an intense battle
      for evolutionary dominance due to the asymmetric retention of only one product of
      female meiosis.

PMID- 19766563
TI  - The tumor suppressor p53 regulates polarity of self-renewing divisions in mammary
      stem cells.
AB  - Stem-like cells may be integral to the development and maintenance of human
      cancers. Direct proof is still lacking, mainly because of our poor understanding
      of the biological differences between normal and cancer stem cells (SCs). Using
      the ErbB2 transgenic model of breast cancer, we found that self-renewing
      divisions of cancer SCs are more frequent than their normal counterparts,
      unlimited and symmetric, thus contributing to increasing numbers of SCs in
      tumoral tissues. SCs with targeted mutation of the tumor suppressor p53 possess
      the same self-renewal properties as cancer SCs, and their number increases
      progressively in the p53 null premalignant mammary gland. Pharmacological
      reactivation of p53 correlates with restoration of asymmetric divisions in cancer
      SCs and tumor growth reduction, without significant effects on additional cancer
      cells. These data demonstrate that p53 regulates polarity of cell division in
      mammary SCs and suggest that loss of p53 favors symmetric divisions of cancer
      SCs, contributing to tumor growth.

PMID- 19766564
TI  - Molecular architecture of the Mos1 paired-end complex: the structural basis of
      DNA transposition in a eukaryote.
AB  - A key step in cut-and-paste DNA transposition is the pairing of transposon ends
      before the element is excised and inserted at a new site in its host genome.
      Crystallographic analyses of the paired-end complex (PEC) formed from precleaved
      transposon ends and the transposase of the eukaryotic element Mos1 reveals two
      parallel ends bound to a dimeric enzyme. The complex has a trans arrangement,
      with each transposon end recognized by the DNA binding region of one transposase
      monomer and by the active site of the other monomer. Two additional DNA duplexes
      in the crystal indicate likely binding sites for flanking DNA. Biochemical data
      provide support for a model of the target capture complex and identify Arg186 to
      be critical for target binding. Mixing experiments indicate that a transposase
      dimer initiates first-strand cleavage and suggest a pathway for PEC formation.

PMID- 19766565
TI  - Recombinational repair within heterochromatin requires ATP-dependent chromatin
      remodeling.
AB  - Heterochromatin plays a key role in protection of chromosome integrity by
      suppressing homologous recombination. In Saccharomyces cerevisiae, Sir2p, Sir3p,
      and Sir4p are structural components of heterochromatin found at telomeres and the
      silent mating-type loci. Here we have investigated whether incorporation of Sir
      proteins into minichromosomes regulates early steps of recombinational repair in
      vitro. We find that addition of Sir3p to a nucleosomal substrate is sufficient to
      eliminate yRad51p-catalyzed formation of joints, and that this repression is
      enhanced by Sir2p/Sir4p. Importantly, Sir-mediated repression requires histone
      residues that are critical for silencing in vivo. Moreover, we demonstrate that
      the SWI/SNF chromatin-remodeling enzyme facilitates joint formation by evicting
      Sir3p, thereby promoting subsequent Rad54p-dependent formation of a strand
      invasion product. These results suggest that recombinational repair in the
      context of heterochromatin presents additional constraints that can be overcome
      by ATP-dependent chromatin-remodeling enzymes.

PMID- 19766566
TI  - Histone crosstalk between H3S10ph and H4K16ac generates a histone code that
      mediates transcription elongation.
AB  - The phosphorylation of the serine 10 at histone H3 has been shown to be important
      for transcriptional activation. Here, we report the molecular mechanism through
      which H3S10ph triggers transcript elongation of the FOSL1 gene. Serum stimulation
      induces the PIM1 kinase to phosphorylate the preacetylated histone H3 at the
      FOSL1 enhancer. The adaptor protein 14-3-3 binds the phosphorylated nucleosome
      and recruits the histone acetyltransferase MOF, which triggers the acetylation of
      histone H4 at lysine 16 (H4K16ac). This histone crosstalk generates the
      nucleosomal recognition code composed of H3K9acS10ph/H4K16ac determining a
      nucleosome platform for the bromodomain protein BRD4 binding. The recruitment of
      the positive transcription elongation factor b (P-TEFb) via BRD4 induces the
      release of the promoter-proximal paused RNA polymerase II and the increase of its
      processivity. Thus, the single phosphorylation H3S10ph at the FOSL1 enhancer
      triggers a cascade of events which activate transcriptional elongation.

PMID- 19766567
TI  - Identification of an Aurora-A/PinsLINKER/Dlg spindle orientation pathway using
      induced cell polarity in S2 cells.
AB  - Asymmetric cell division is intensely studied because it can generate cellular
      diversity as well as maintain stem cell populations. Asymmetric cell division
      requires mitotic spindle alignment with intrinsic or extrinsic polarity cues, but
      mechanistic detail of this process is lacking. Here, we develop a method to
      construct cortical polarity in a normally unpolarized cell line and use this
      method to characterize Partner of Inscuteable (Pins; LGN/AGS3 in mammals) 
      dependent spindle orientation. We identify a previously unrecognized
      evolutionarily conserved Pins domain (Pins(LINKER)) that requires Aurora-A
      phosphorylation to recruit Discs large (Dlg; PSD-95/hDlg in mammals) and promote
      partial spindle orientation. The well-characterized Pins(TPR) domain has no
      function alone, but placing the Pins(TPR) in cis to the Pins(LINKER) gives dynein
      dependent precise spindle orientation. This "induced cortical polarity" assay is
      suitable for rapid identification of the proteins, domains, and amino acids
      regulating spindle orientation or cell polarity.

PMID- 19766568
TI  - Detecting folding intermediates of a protein as it passes through the bacterial
      translocation channel.
AB  - Most bacterial exported proteins cross the cytoplasmic membrane as unfolded
      polypeptides. However, little is known about how they fold during or after this
      process due to the difficulty in detecting folding intermediates. Here we
      identify cotranslational and posttranslational folding intermediates of a
      periplasmic protein in which the protein and DsbA, a periplasmic disulfide bond
      forming enzyme, are covalently linked by a disulfide bond. The cotranslational
      mixed-disulfide intermediate is, upon further chain elongation, resolved,
      releasing the oxidized polypeptide, thus allowing us to follow the folding
      process. This analysis reveals that two cysteines that are joined to form a
      structural disulfide can play different roles during the folding reaction and
      that the mode of translocation (cotranslational verse posttranslational) can
      affect the folding process of a protein in the periplasm. The latter finding
      leads us to propose that the activity of the ribosome (translation) can modulate
      protein folding even in an extracytosolic compartment.

PMID- 19766569
TI  - Kinesin-8 motors act cooperatively to mediate length-dependent microtubule
      depolymerization.
AB  - Motor proteins in the kinesin-8 family depolymerize microtubules in a length
      dependent manner that may be crucial for controlling the length of organelles
      such as the mitotic spindle. We used single-molecule microscopy to understand the
      mechanism of length-dependent depolymerization by the budding yeast kinesin-8,
      Kip3p. We found that after binding at a random position on a microtubule and
      walking to the plus end, an individual Kip3p molecule pauses there until an
      incoming Kip3p molecule bumps it off. Kip3p dissociation is accompanied by
      removal of just one or two tubulin dimers (on average). Such a cooperative
      mechanism leads to a depolymerization rate that is proportional to the flux of
      motors to the microtubule end and accounts for the length dependence of
      depolymerization. This type of feedback between length and disassembly may serve
      as a model for understanding how an ensemble of molecules can measure and control
      polymer length.

PMID- 19766570
TI  - CHL1 functions as a nitrate sensor in plants.
AB  - Ions serve as essential nutrients in higher plants and can also act as signaling
      molecules. Little is known about how plants sense changes in soil nutrient
      concentrations. Previous studies showed that T101-phosphorylated CHL1 is a high
      affinity nitrate transporter, whereas T101-dephosphorylated CHL1 is a low
      affinity transporter. In this study, analysis of an uptake- and sensing-decoupled
      mutant showed that the nitrate transporter CHL1 functions as a nitrate sensor.
      Primary nitrate responses in CHL1T101D and CHLT101A transgenic plants showed that
      phosphorylated and dephosphorylated CHL1 lead to a low- and high-level response,
      respectively. In vitro and in vivo studies showed that, in response to low
      nitrate concentrations, protein kinase CIPK23 can phosphorylate T101 of CHL1 to
      maintain a low-level primary response. Thus, CHL1 uses dual-affinity binding and
      a phosphorylation switch to sense a wide range of nitrate concentrations in the
      soil, thereby functioning as an ion sensor in higher plants. For a video summary
      of this article, see the PaperFlick file with the Supplemental Data available
      online.

PMID- 19766571
TI  - Actomyosin is the main driver of interkinetic nuclear migration in the retina.
AB  - Progenitor cell nuclei in the rapidly expanding epithelium of the embryonic
      vertebrate central nervous system undergo a process called interkinetic nuclear
      migration (IKNM). Movements of IKNM are generally believed to involve smooth
      migration of nuclei from apical to basal and back during the G1 and G2 phases of
      the cell cycle, respectively. Yet, this has not been formally demonstrated, nor
      have the molecular mechanisms that drive IKNM been identified. Using time-lapse
      confocal microscopy to observe nuclear movements in zebrafish retinal
      neuroepithelial cells, we show that, except for brief apical nuclear
      translocations preceding mitosis, IKNM is stochastic rather than smooth and
      directed. We also show that IKNM is driven largely by actomyosin-dependent forces
      as it still occurs when the microtubule cytoskeleton is compromised but is
      blocked when MyosinII activity is inhibited.

PMID- 19766572
TI  - The antioxidant enzyme Prdx1 controls neuronal differentiation by thiol-redox
      dependent activation of GDE2.
AB  - The six-transmembrane protein GDE2 controls the onset and progression of spinal
      motor neuron differentiation through extracellular glycerophosphodiester
      phosphodiesterase metabolism. Although this process is likely to be tightly
      regulated, the relevant mechanisms that modulate its activity are unknown. Here
      we show that the antioxidant scavenger peroxiredoxin1 (Prdx1) interacts with
      GDE2, and that loss of Prdx1 causes motor neuron deficits analogous to GDE2
      ablation. Prdx1 cooperates with GDE2 to drive motor neuron differentiation, and
      this synergy requires Prdx1 thiol-dependent catalysis. Prdx1 activates GDE2
      through reduction of an intramolecular disulfide bond that bridges its
      intracellular N- and C-terminal domains. GDE2 variants incapable of disulfide
      bond formation acquire independence from Prdx1 and are potent inducers of motor
      neuron differentiation. These findings define Prdx1 as a pivotal regulator of
      GDE2 activity and suggest roles for coupled thiol-redox-dependent cascades in
      controlling neuronal differentiation in the spinal cord.

PMID- 19766574
TI  - SnapShot: Antibiotic inhibition of protein synthesis I.

PMID- 19766573
TI  - Synaptic PRG-1 modulates excitatory transmission via lipid phosphate-mediated
      signaling.
AB  - Plasticity related gene-1 (PRG-1) is a brain-specific membrane protein related to
      lipid phosphate phosphatases, which acts in the hippocampus specifically at the
      excitatory synapse terminating on glutamatergic neurons. Deletion of prg-1 in
      mice leads to epileptic seizures and augmentation of EPSCs, but not IPSCs. In
      utero electroporation of PRG-1 into deficient animals revealed that PRG-1
      modulates excitation at the synaptic junction. Mutation of the extracellular
      domain of PRG-1 crucial for its interaction with lysophosphatidic acid (LPA)
      abolished the ability to prevent hyperexcitability. As LPA application in vitro
      induced hyperexcitability in wild-type but not in LPA(2) receptor-deficient
      animals, and uptake of phospholipids is reduced in PRG-1-deficient neurons, we
      assessed PRG-1/LPA(2) receptor-deficient animals, and found that the
      pathophysiology observed in the PRG-1-deficient mice was fully reverted. Thus, we
      propose PRG-1 as an important player in the modulatory control of hippocampal
      excitability dependent on presynaptic LPA(2) receptor signaling.

PMID- 19766575
TI  - Pre-analytical and analytical considerations for the determination of plasma
      renin activity.
AB  - BACKGROUND: Primary hyperaldosteronism diagnosis is helped by assaying renin
      concentrations either by immunodetection (active renin) or by enzymatic reaction
      followed by angiotensin I immunoassay (plasma renin activity). We investigated
      the impact of pre-analytical and analytical conditions on a PRA assay. METHODS:
      PRA was assayed using a commercial kit. Firstly, a retrospective analysis of PRA
      results from 1yr was performed. Secondly, the impact of pre-analytical
      temperature conveyance/storage of samples was tested (4 and 25 degrees C).
      Thirdly, 2 durations of enzymatic reaction 1.5 and 18h were tested. RESULTS:
      Retrospectively, 9.5% samples displayed elevated "blanks": calculating PRA with
      or without "blank" subtraction elicited a difference of >10% in 1/3 samples.
      There was a significant decrease of PRA values in samples left at 25 degrees C vs
      4 degrees C (50% "blank" increase). Finally, the longer the enzymatic reaction
      (1.5 vs 18h), the higher the production of angiotensin I and the better the PRA
      assay sensitivity. CONCLUSION: We propose a 2 step procedure: a brief 1.5h
      enzymatic reaction time followed by a prolonged reaction (18h) only if PRA is
      <0.2ng mL(-1) h(-1). We would recommend performing "blank" samples for the brief
      enzymatic reaction time. Finally, conveyance/storage temperature does modify PRA
      results albeit in our hands this had little clinical impact.

PMID- 19766576
TI  - Influenza recombinant vaccine: matrix protein M1 on the platform of the
      adenovirus dodecahedron.
AB  - We propose a novel influenza vaccine composed of the adenovirus dodecahedron (Dd)
      as delivery platform carrying an internal influenza matrix protein M1. To attach
      the antigen to the vector we used WW domains interacting with Dd. Successful
      internalization of the Dd-M1WW complex was observed using biochemical and cell
      biology techniques. We show here that the complex of Dd with antigen is a potent
      activator of human myeloid dendritic cells (MDC), and that it is efficiently
      presented by MDC to M1-specific CD8+ T lymphocytes. These results show that
      proposed vaccine model is feasible and that adenovirus dodecahedron is a potent
      delivery platform for foreign antigens to human cells.

PMID- 19766578
TI  - Coordination of the EEG and the heart rate of preterm neonates during quiet
      sleep.
AB  - Aim of this study was to confirm that EEG bursts are associated with heart rate
      (HR) accelerations, and to investigate the synchronicity between quadratic phase
      couplings (QPC) courses of the EEG and HR before and during burst activity during
      quiet sleep in preterm newborns. The time-courses of QPC between frequency
      components of the EEG ([0.25-1.0 Hz]<-->[4.0-6.0 Hz]) as well as between the
      Mayer-Traube-Hering (MTH) wave and the frequency component of the HR associated
      to the respiratory sinus arrhythmia (RSA) ([0.02-0.15 Hz]<-->[0.4-1.5 Hz]) were
      investigated in five preterm neonates. During quiet sleep, the EEG alternates
      between burst and interburst activity. The burst onsets were used to trigger an
      averaging procedure for the EEG, HR, and QPC courses. It can be demonstrated that
      the envelopes of the EEG rise after the burst onset accompanied by an
      acceleration of HR before or at the burst maximum. The QPC courses show that the
      HR's QPC increases before or at the burst onset whereas the increase of the EEG's
      QPC is delayed. The synchronous changes of EEG and HR as well as of the
      corresponding QPC courses indicate a coupling between cortical, thalamocortical
      and neurovegetative brain structures. Such a coupling might be mediated by the
      MTH waves in the blood pressure.

PMID- 19766577
TI  - Risk of immune hemolytic anemia in children following immunization.
AB  - Several case reports have described immune hemolytic anemia (IHA) following
      vaccination in children. We examined the risk of IHA in the 42 days following
      vaccination exposure using a self-controlled case series study design. In our
      population-based cohort of nearly 4.5 million children in the Vaccine Safety
      Datalink, we identified 55 confirmed cases of new-onset IHA from 1991 through
      2000. We found no association between IHA and diphtheria-pertussis-tetanus
      vaccination (incidence rate ratio (IRR)=0.65, 95% CI: 0.19-2.24), hepatitis B
      vaccination (IRR=1.73, 95% CI: 0.59-5.01), or any vaccination (IRR=1.04, 95% CI:
      0.46-2.32).

PMID- 19766579
TI  - No association between chronic cannabis use and loudness dependence of auditory
      evoked potentials as indicator of central serotonergic neurotransmission.
AB  - Chronic cannabis use has been found to be associated with major depression. It is
      suggested that cannabis use induces changes in neurotransmitter systems involved
      in the pathogenesis of depressive disorders, particularly in the serotonergic
      system. The analysis of the loudness dependence of auditory evoked potentials
      (LDAEP) is a valid non-invasive indicator of central serotonergic activity in
      animals and humans. In the present study, we investigated the effects of chronic
      cannabis use on LDAEP in 30 psychiatrically unaffected users compared to 30 non
      user controls. Users were required to abstain from cannabis for at least 24 h
      before testing. Putative depressive symptoms were assessed by using the Beck
      Depression Inventory (BDI) and the Hamilton Rating Scale for Depression (HAMD
      21). LDAEP as well as BDI and HAMD-21 scores did not differ between cannabis
      users and controls. Moreover, LDAEP neither correlate with duration and quantity
      of cannabis use nor with psychometric assessments. These results indicate that
      chronic cannabis use had no influence on the LDAEP in this study sample. It can
      be suggested that significant alterations in serotonergic systems may rather be
      related to acute activation of the endogenous cannabinoid system or to cannabis
      dependence accompanied by manifest depressive symptoms.

PMID- 19766580
TI  - A comparison of dedicated 1.0 T extremity MRI vs large-bore 1.5 T MRI for
      semiquantitative whole organ assessment of osteoarthritis: the MOST study.
AB  - OBJECTIVE: To date semiquantitative whole-organ scoring of knee osteoarthritis
      (OA) relies on 1.5 Tesla (T) Magnetic resonance imaging (MRI) systems. Less
      costly 1.0 T extremity systems have been introduced that offer superior patient
      comfort, but may have limitations concerning field-of-view and image quality. The
      aim of this study was to compare semi-quantitative (SQ) scoring on a 1.0 T system
      using 1.5 T MRI as the standard of reference. METHODS: The Multicenter
      Osteoarthritis Study (MOST) is a longitudinal study of individuals who have or
      are at high risk for knee OA. A sample of 53 knees was selected in which MRI was
      performed on a 1.0 T extremity system as well as on a 1.5 T scanner applying a
      comparable sequence protocol. MRIs were read according to the Whole Organ
      Magnetic Resonance Imaging Score (WORMS) score. Agreement was determined using
      weighted kappa statistics. Sensitivity, specificity and accuracy were assessed
      using the 1.5 T readings as the reference standard. In addition the number of non
      readable features was assessed. RESULTS: Agreement (w-kappa) for seven main WORMS
      features (cartilage, bone marrow lesions (BMLs), osteophytes, meniscal damage and
      extrusion, synovitis, effusion) ranged between 0.54 (synovitis) and 0.75
      (cartilage). Sensitivity ranged between 68.1% (meniscal damage) and 88.1%
      (effusion). Specificity ranged between 63.6% (effusion) and 96.4% (BMLs).
      Although the overall rate of non-readable features was very low, it was higher
      for the 1.0 T system (1.9% vs 0.2%). CONCLUSIONS: Semiquantitative whole organ
      scoring can be performed using a 1.0 T peripheral scanner with a moderate to high
      degree of agreement and accuracy compared to SQ assessment using a 1.5 T whole
      body scanner. Our results are comparable to the published inter- and intra
      observer exercises obtained from 1.5 T systems. Sensitivity to change of
      longitudinal scoring was not evaluated in this cross-sectional design and should
      be investigated in future validation studies.

PMID- 19766581
TI  - Modular plastic chip for one-shot human papillomavirus diagnostic analysis.
AB  - In this article, we report the design and development of a plastic modular chip
      suitable for one-shot human papillomavirus (HPV) diagnostics, namely detection of
      the viral presence and relative genotyping, by two sequential steps performed
      directly on the same device. The device is composed of two modular and disposable
      plastic units that can be assembled or used separately. The first module is
      represented by a polydimethylsiloxane (PDMS) microreactor that is exploited for
      real-time polymerase chain reaction (PCR) and, thus, is suitable for detecting
      the presence of virus. The second unit is a PDMS microwell array that allows
      virus genotyping by a colorimetric assay, based on DNA hybridization technology
      developed on plastic, requiring simple inspection by the naked eye. The two
      modules can be easily coupled to reusable hardware, enabling the heating/cooling
      processes and the real-time detection of HPV. By coupling real-time assay and
      colorimetric genotyping on the same chip, the assembled device may provide a low
      cost tool for HPV diagnostics, thereby favoring the prediction of cancer risk in
      patients.

PMID- 19766582
TI  - Comparison of methods for measuring oxygen consumption in tumor cells in vitro.
AB  - The oxygen consumption rate of tumor cells affects tumor oxygenation and response
      to therapies. Highly sensitive methods for determining cellular oxygen
      consumption are, therefore, needed to identify treatments that can modulate this
      parameter. We compared the performances of three different methods for measuring
      cellular oxygen consumption: electron paramagnetic resonance (EPR) oximetry, the
      Clark electrode, and the MitoXpress fluorescent assay. To compare the assays, we
      used K562 cells in the presence of rotenone and hydrocortisone, compounds that
      are known to inhibit the mitochondrial electron transport chain to different
      extents. The EPR method was the only one that could identify both rotenone and
      hydrocortisone as inhibitors of tumor cell oxygen consumption. The Clark
      electrode and the fluorescence assay demonstrated a significant decrease in
      cellular oxygen consumption after administration of the most potent inhibitor
      (rotenone) but failed to show any significant effect of hydrocortisone. EPR
      oximetry is, therefore, the most sensitive method for identifying inhibitors of
      oxygen consumption on cell assays, whereas the Clark electrode offers the unique
      opportunity to add external compounds during experiments and still shows great
      sensitivity in studying enzyme and chemical reactions that consume oxygen (non
      cell assays). Finally, the MitoXpress fluorescent assay has the advantage of a
      high-sample throughput and low bulk requirements but at the cost of a lower
      sensitivity.

PMID- 19766583
TI  - Studies in serum support rapid formation of disulfide bond between unpaired
      cysteine residues in the VH domain of an immunoglobulin G1 molecule.
AB  - Recombinant monoclonal antibodies undergo extensive posttranslational
      modifications. In this article, we characterize major modifications, separated by
      cation exchange chromatography, on an immunoglobulin G1 (IgG1) monoclonal
      antibody (mAb). We found that N-terminal cyclization of glutamine residues to
      pyroglutamate on the light and heavy chains are the major isoforms resolved
      during cation exchange chromatography. However, using CEX, we also separated and
      identified isoforms with unpaired cysteine residues in the V(H) domain of the
      molecule (Cys22-Cys96). Omalizumab, a therapeutic anti-IgE antibody, has unpaired
      cysteine residues in the V(H) domain between Cys22 and Cys96, and the Fab
      fragment, containing the unpaired cysteine residues, is reported to have reduced
      potency. Dynamic interchain disulfide rearrangement, with slow kinetics, was
      recently reported to take place in serum for an IgG2 molecule and resulted in
      predictable mature isoforms. Analytical evaluation of our mAb, after recovery
      from serum, revealed that the unpaired intrachain cysteine residues (Cys22-Cys96)
      reformed their disulfide bond. The significance of this study is that correct
      pairing occurred rapidly, and we speculate that thiol molecules such as cysteine,
      homocysteine, and glutathione in serum provide an environment, outside the
      endoplasmic reticulum, for correct linkage.

PMID- 19766584
TI  - Production of dimethyl triselenide and dimethyl diselenenyl sulfide in the
      headspace of metalloid-resistant Bacillus species grown in the presence of
      selenium oxyanions.
AB  - A Bacillus species harvested from the environment is metalloid resistant and,
      when grown anaerobically in complex growth medium and amended with the selenium
      oxyanion selenate, selenite, or selenocyanate, produces volatile organoselenium
      compounds in bacterial culture headspace. Two novel compounds so far undetected
      in bacterial culture headspace, CH3Se2SCH3 and CH3SeSeSeCH3, are produced and can
      be detected using solid-phase microextraction and gas chromatography with either
      fluorine-induced chemiluminescence or mass spectrometric detection. Differences
      in the electron impact fragmentation pattern of the mixed sulfur/selenide
      compounds allow the tentative differentiation between the symmetric and
      asymmetric isomers in this bacterium's headspace in favor of the asymmetric
      CH3SeSeSCH3 isomer.

PMID- 19766585
TI  - A flow injection system, comprising a biosensor based on a screen-printed carbon
      electrode containing Meldola's Blue-Reinecke salt coated with glucose
      dehydrogenase, for the measurement of glucose.
AB  - A biosensor for the measurement of glucose in serum has been developed, based on
      a screen-printed carbon electrode modified with Meldola's Blue-Reinecke salt,
      coated with the enzyme glucose dehydrogenase (from Bacillus sp.), and
      nicotinamide adenine dinucleotide coenzyme (NAD+). A cellulose acetate layer was
      deposited on top of the device to act as a permselective membrane. The biosensor
      was incorporated into a commercially available, thin-layer, amperometric flow
      cell operated at a potential of only +0.05 V versus Ag/AgCl. The mobile phase
      consisted of 0.2 M phosphate buffer (pH 7.0) containing 0.1 M potassium chloride
      solution, and a flow rate of 0.8 ml min(-1) was used throughout the
      investigation. The biosensor response was linear over the range of 0.075-30 mM
      glucose, with the former representing the detection limit. The precision of the
      system was determined by carrying out 20 repeat injections of a 5-mM glucose
      standard, and the calculated coefficient of variation was 3.9%. It was
      demonstrated that this biosensor system could be applied to the direct
      measurement of glucose in serum without pretreatment. Therefore, this would allow
      high-throughput analysis, at low cost, for this clinically important analyte.

PMID- 19766586
TI  - ADAM8 substrate specificity: influence of pH on pre-processing and proteoglycan
      degradation.
AB  - A disintegrin and metalloprotease-8 (ADAM8) is thought to play a role in cancer
      and inflammatory diseases such as allergy, arthritis, and asthma. Despite the
      implication of ADAM8 in these diseases, the functional role of ADAM8 catalytic
      activity remains unclear. In this report, we demonstrate that an early critical
      autolytic event, we have termed pre-processing, is accelerated at acidic pH (pH
      5.5) while autolytic activation is abrogated under the same conditions. Likewise,
      we found that pre-processing is hindered and autolytic activation is facilitated
      in neutral pH conditions, and thus demonstrates a pH-dependent shift in substrate
      selectivity. This finding is further supported by two peptide substrates
      corresponding to the pre-processing and C-terminal scissile bonds that were
      preferentially cleaved at acidic and neutral pH, respectively. Lastly, we found
      fibronectin cleavage to be attenuated at pH 5.5, while two novel substrates,
      brevican, and vitronectin, were readily cleaved in neutral or acidic conditions.

PMID- 19766587
TI  - Kinetic and structural features of betaine aldehyde dehydrogenases: mechanistic
      and regulatory implications.
AB  - The betaine aldehyde dehydrogenases (BADH; EC 1.2.1.8) are so-called because they
      catalyze the irreversible NAD(P)(+)-dependent oxidation of betaine aldehyde to
      glycine betaine, which may function as (i) a very efficient osmoprotectant
      accumulated by both prokaryotic and eukaryotic organisms to cope with osmotic
      stress, (ii) a metabolic intermediate in the catabolism of choline in some
      bacteria such as the pathogen Pseudomonas aeruginosa, or (iii) a methyl donor for
      methionine synthesis. BADH enzymes can also use as substrates aminoaldehydes and
      other quaternary ammonium and tertiary sulfonium compounds, thereby participating
      in polyamine catabolism and in the synthesis of gamma-aminobutyrate, carnitine,
      and 3-dimethylsulfoniopropionate. This review deals with what is known about the
      kinetics and structural properties of these enzymes, stressing those properties
      that have only been found in them and not in other aldehyde dehydrogenases, and
      discussing their mechanistic and regulatory implications.

PMID- 19766588
TI  - Rice family GH1 glycoside hydrolases with beta-D-glucosidase and beta-D
      mannosidase activities.
AB  - Plant beta-D-mannosidases and a rice beta-D-glucosidase, Os3BGlu7, with weak beta
      D-mannosidase activity, cluster together in phylogenetic analysis. To investigate
      the relationship between substrate specificity and amino acid sequence similarity
      in family GH1 glycoside hydrolases, Os3BGlu8 and Os7BGlu26, putative rice beta-D
      glucosidases from this cluster, and a beta-D-mannosidase from barley (rHvBII),
      were expressed in Escherichia coli and characterized. Os3BGlu8, the amino acid
      sequence and molecular model of which are most similar to Os3BGlu7, hydrolysed 4
      nitrophenyl-beta-D-glucopyranoside (4NPGlc) faster than 4-nitrophenyl-beta-D
      mannopyranoside (4NPMan), while Os7BGlu26, which is most similar to rHvBII by
      these criteria, hydrolysed 4NPMan faster than 4NPGlc. All the enzymes hydrolyzed
      cellooligosaccharides with increased hydrolytic rates as the degree of
      polymerization increased from 3-6, but only rHvBII hydrolyzed cellobiose with a
      higher k(cat)/K(m) value than cellotriose. This was primarily due to strong
      binding of glucosyl residues at the+2 subsite for the rice enzymes, and
      unfavorable interactions at this subsite with rHvBII.

PMID- 19766589
TI  - Tuning the insertion properties of pHLIP.
AB  - The pH (low) insertion peptide (pHLIP) has exceptional characteristics: at
      neutral pH it is an unstructured monomer in solution or when bound to lipid
      bilayer surfaces, and it inserts across a lipid bilayer as a monomeric alpha
      helix at acidic pH. The peptide targets acidic tissues in vivo and may be useful
      in cancer biology for delivery of imaging or therapeutic molecules to acidic
      tumors. To find ways to vary its useful properties, we have designed and analyzed
      pHLIP sequence variants. We find that each of the Asp residues in the
      transmembrane segment is critical for solubility and pH-dependent membrane
      insertion of the peptide. Changing both of the Asp residues in the transmembrane
      segment to Glu, inserting an additional Asp into the transmembrane segment, or
      replacing either of the Asp residues with Ala leads to aggregation and/or loss of
      pH-dependent membrane insertion of the peptide. However, variants with either of
      the Asp residues changed to Glu remained soluble in an aqueous environment and
      inserted into the membrane at acidic pH with a higher pK(app) of membrane
      insertion.

PMID- 19766590
TI  - Silica xerogel/aerogel-supported lipid bilayers: consequences of surface
      corrugation.
AB  - The objective of this paper was to review our recent investigations of silica
      xerogel and aerogel-supported lipid bilayers. These systems provide a format to
      observe relationships between substrate curvature and supported lipid bilayer
      formation, lipid dynamics, and lipid mixtures phase behavior and partitioning.
      Sensitive surface techniques such as quartz crystal microbalance and atomic force
      microscopy are readily applied to these systems. To inform current and future
      investigations, we review the experimental literature involving the impact of
      curvature on lipid dynamics, lipid and phase-separated lipid domain localization,
      and membrane-substrate conformations and we review our molecular dynamics
      simulations of supported lipid bilayers with the atomistic and molecular
      information they provide.

PMID- 19766591
TI  - Mitochondrial apoptosis is amplified through gap junctions.
AB  - The death of one cell can precipitate the death of nearby cells in a process
      referred to as the bystander effect. We investigated whether mitochondrial
      apoptosis generated a bystander effect and, if so, by which pathway.
      Microinjection with cytochrome c mimicked function of the mitochondrial apoptosis
      induced channel MAC and caused apoptosis of both target and nearby osteoblasts.
      This effect was suppressed by inhibiting gap junction intercellular
      communication. A bystander effect was also observed after exogenous expression of
      tBid, which facilitates MAC formation and cytochrome c release. Interestingly, in
      connexin-43 deficient osteoblasts, microinjection of cytochrome c induced
      apoptosis only in the target cell. These findings indicate that a death signal
      was generated downstream of MAC function and was transmitted through gap
      junctions to amplify apoptosis in neighboring cells. This concept may have
      implications in development of new therapeutic approaches.

PMID- 19766592
TI  - DNA polymerase mu interacts with a meiosis-specific RecA homolog Lim15 during
      meiosis in Coprinus cinereus.
AB  - Meiosis is a fundamental process in eukaryotes. Homologous chromosomes are paired
      and recombined during meiotic prophase I, which results in variation among the
      gametes. However, the mechanism of recombination between the maternal and
      paternal chromosome is unknown. In this study, we report on the identification of
      interaction between Coprinus cinereus DNA polymerase mu (CcPol mu) and
      CcLim15/Dmc1, a meiosis-specific RecA-like protein, during meiosis. Interaction
      between these two proteins was confirmed using a GST-pull down assay. A two
      hybrid assay revealed that the N-terminus of CcPol mu, which includes the BRCT
      domain, is responsible for binding the C-terminus of CcLim15. Furthermore, co
      immunoprecipitation experiments indicate that these two proteins also interact in
      the crude extract of the meiotic cell. A significant proportion of CcPol mu and
      CcLim15 is shown to co-localize in nuclei from the leptotene/zygotene stage to
      the early pachytene stage during meiotic prophase I. Moreover, CcLim15 enhances
      polymerase activity of CcPol mu early in the reaction. These results suggest that
      CcPol mu might be recruited by CcLim15 and elongate the D-loop structure during
      homologous recombination in meiosis.

PMID- 19766593
TI  - Letter of rebuttal and apology to editor on the retraction of "Velocity of
      polymer translocation through a pore".

PMID- 19766594
TI  - NMR solution structure of human cannabinoid receptor-1 helix 7/8 peptide:
      candidate electrostatic interactions and microdomain formation.
AB  - We report the NMR solution structure of a synthetic 40-mer (T(377)-E(416)) that
      encompasses human cannabinoid receptor-1 (hCB1) transmembrane helix 7 (TMH7) and
      helix 8 (H8) [hCB1(TMH7/H8)] in 30% trifluoroethanol/H(2)O. Structural features
      include, from the peptide's amino terminus, a hydrophobic alpha-helix (TMH7); a
      loop-like, 11 residue segment featuring a pronounced Pro-kink within the
      conserved NPxxY motif; a short amphipathic alpha-helix (H8) orthogonal to TMH7
      with cationic and hydrophobic amino-acid clusters; and an unstructured C-terminal
      end. The hCB1(TMH7/H8) NMR solution structure suggests multiple electrostatic
      amino-acid interactions, including an intrahelical H8 salt bridge and a hydrogen
      bond network involving the peptide's loop-like region. Potential cation-pi and
      cation-phenolic OH interactions between Y(397) in the TMH7 NPxxY motif and R(405)
      in H8 are identified as candidate structural forces promoting interhelical
      microdomain formation. This microdomain may function as a flexible molecular
      hinge during ligand-induced hCB1 conformer transitions.

PMID- 19766595
TI  - Isolation of a novel leptin receptor gene promoter preferentially functioning in
      neuronal cells.
AB  - Leptin exerts its metabolic effects by binding to the leptin receptor (Ob-R). In
      humans, the promoter of the Ob-R gene-related protein (Ob-RGRP) gene and the
      B219/Ob-R promoter have been speculated to spatially and temporarily regulate Ob
      R gene transcription; however, the promoter function of the Ob-R gene has not
      been directly analyzed. Using 5' rapid amplification of the cDNA end, we isolated
      novel ob-r transcripts starting from the 3' portions of the B219/ob-r 5'
      untranslated region in the adult mouse brain. The proximal promoter containing
      these start sites showed robust activity in neuron-derived, but not non-neuronal
      cell lines. The promoter activity was comparable with that of the ob-rgrp
      promoter in a neuronal cell, but significantly weaker in non-neuronal cells.
      Deletion analyses identifying two enhancer elements were located in this
      promoter. The identification of a novel ob-r gene promoter might provide a useful
      tool to study neuron specific expression and hormonal regulation of the ob-r
      gene.

PMID- 19766596
TI  - Positive auto-regulation of MYCN in human neuroblastoma.
AB  - MYCN oncogene is one of the most important regulators affecting the prognosis of
      neuroblastoma and is frequently amplified in the high-risk subsets. Despite its
      clinical significance, it remains unclear how the MYCN expression is regulated in
      human neuroblastomas. Here, we found the presence of a positive auto-regulatory
      mechanism of MYCN. Enforced expression of MYCN induced endogenous MYCN mRNA
      expression in SK-N-AS neuroblastoma cells with a single copy of MYCN gene.
      Luciferase reporter assay revealed that MYCN protein activates its own promoter
      activity in a dose-dependent manner and the downstream region relative to the
      transcription start sites is responsible for the activation. Furthermore, ChIP
      analysis showed that MYCN is directly recruited onto the intron 1 region of MYCN
      gene which contains two putative E-box sites. Intriguingly, in response to all
      trans-retinoic acid (ATRA), MYCN was down-regulated in MYCN-amplified SK-N-BE
      neuroblastoma cells, and the recruitment of MYCN protein onto its own intron 1
      region was reduced in association with an induction of neuronal differentiation.
      Collectively, our present results suggest that MYCN contributes to its own
      expression by forming a positive auto-regulatory loop in neuroblastoma cells.

PMID- 19766597
TI  - Loss of gap junctional intercellular communication in rat lung epithelial cells
      exposed to quartz particles.
AB  - Chronic inhalation of quartz particles has been implicated in lung diseases
      including silicosis and cancer. The aim of this study was to investigate whether
      quartz particles affect gap junctional intercellular communication (GJIC) in rat
      lung epithelial cells (RLE-6TN). Here, we demonstrate that exposure of RLE-6TN
      cells to subtoxic doses of DQ12 standard quartz resulted in an up to 55%
      reduction of GJIC, as determined in a dye transfer assay. We show that connexin
      43 (Cx43) is the major connexin responsible for intercellular communication in
      these lung epithelial cells and that exposure to quartz particles induces a
      significant internalization of Cx43. Downregulation of GJIC was attenuated by N
      acetyl cysteine, suggesting the involvement of reactive oxygen species and/or
      cellular thiol homeostasis in the regulation of GJIC. Furthermore, an inhibitor
      of activation of extracellular signal-regulated kinases prevented the loss of
      GJIC in cells exposed to DQ12 quartz, although no direct phosphorylation of Cx43
      upon exposure to DQ12 was detected.

PMID- 19766598
TI  - Imaging exocytosis of single glucagon-like peptide-1 containing granules in a
      murine enteroendocrine cell line with total internal reflection fluorescent
      microscopy.
AB  - To analyze the exocytosis of glucagon-like peptide-1 (GLP-1) granules, we imaged
      the motion of GLP-1 granules labeled with enhanced yellow fluorescent protein
      (Venus) fused to human growth hormone (hGH-Venus) in an enteroendocrine cell
      line, STC-1 cells, by total internal reflection fluorescent (TIRF) microscopy. We
      found glucose stimulation caused biphasic GLP-1 granule exocytosis: during the
      first phase, fusion events occurred from two types of granules (previously docked
      granules and newcomers), and thereafter continuous fusion was observed mostly
      from newcomers during the second phase. Closely similar to the insulin granule
      fusion from pancreatic beta cells, the regulated biphasic exocytosis from two
      types of granules may be a common mechanism in glucose-evoked hormone release
      from endocrine cells.

PMID- 19766599
TI  - Jnk signaling pathway-mediated regulation of Stat3 activation is linked to the
      development of doxorubicin resistance in cancer cell lines.
AB  - We sought to identify altered transcription factors (Stat, AP1, and NF-kB) or
      signal proteins (Erk1/2, p38, Akt, Jnk, Jak, and c-Src) in cancer cell lines
      whose growth was arrested by doxorubicin (DOX) treatment. Jnk1 was the only
      signal protein to be activated. DOX increased Stat3 phosphorylation, nuclear
      localization, and transcriptional activity. Jnk1 activation appeared to be
      required for Stat3 activity. Stat3 activity via the Jnk pathway was conserved in
      other cell lines originating from other organs. Transcriptional activity of Stat3
      was increased in cells surviving DOX treatment suggesting that Stat3 activation
      contributed to the resistance to cytotoxicity. To better understand the role of
      Stat3 in Jnk1 activation, we investigated its effect on the viability of DOX
      treated cells. Co-treatment with DOX and Jnk inhibitor negatively correlated with
      the viability of cancer cells and reduced Stat3 activity. Taken together, these
      results indicate that Stat3 activation via the Jnk pathway promotes the
      resistance of cancer cells to DOX.

PMID- 19766600
TI  - Binding thermodynamics at the human cannabinoid CB1 and CB2 receptors.
AB  - The thermodynamic parameters DeltaG degrees , DeltaH degrees and DeltaS degrees
      of the binding equilibrium of agonists and antagonists at cannabinoid CB(1) and
      CB(2) receptors were determined by means of affinity measurements at different
      temperatures and van't Hoff plots were constructed. Affinity constants were
      measured on CHO cells transfected with the human CB(1) and CB(2) receptors by
      inhibition assays of the binding of the cannabinoid receptor agonist [(3)H]-CP
      55,940. van't Hoff plots were linear for agonists and antagonists in the
      temperature range 0-30 degrees C. The thermodynamic parameters for CB(1)
      receptors fall in the ranges 17< or =DeltaH degrees < or =59 kJ/mol and 213< or
      =DeltaS degrees < or =361 kJ/mol for agonists and -52< or =DeltaH degrees < or =
      26 kJ/mol and -12< or =DeltaS degrees < or =38 kJ/mol for antagonists. The
      thermodynamic parameters for CB(2) receptors fall in the ranges 27< or =DeltaH
      degrees < or =48 kJ/mol and 234< or =DeltaS degrees < or =300 kJ/mol for agonists
      and -19< or =DeltaH degrees < or =-17 kJ/mol and 43< or =DeltaS degrees < or =74
      kJ/mol for antagonists. Collectively, these data show that agonist binding is
      always totally entropy-driven while antagonist binding is enthalpy and entropy
      driven, indicating that CB(1) and CB(2) receptors are thermodynamically
      discriminated. These data could give new details on the nature of the forces
      driving the CB(1) and CB(2) binding at a molecular level. Enthalpy, entropy, free
      energy and binding affinity for each ligand to its receptor can all be assessed
      and therefore the optimal binding profile discovered. Carrying out these binding
      investigations as early as possible in the discovery process increases the
      probability that a lead compound will become a successful pharmaceutical
      compound.

PMID- 19766601
TI  - Ongoing expression of Nkx2.1 in the postnatal mouse forebrain: potential for
      understanding NKX2.1 haploinsufficiency in humans?
AB  - Coordinated movements require the caudate-putamen and the globus pallidus, two
      nuclei belonging to the basal ganglia, to be intact and functioning properly.
      Many neurons populating these regions derive from the medial ganglionic eminence,
      a transient structure that expresses the transcription factor Nkx2.1 during
      prenatal development. Accordingly, the basal ganglia of Nkx2.1(-/-) mice are
      heavily affected and a substantial loss of several types of GABAergic
      interneurons has been observed. Interestingly, heterozygous mutation of the
      NKX2.1 gene in humans has been described as causing an unusual disorder from the
      second year of life onwards, which is mainly characterized by disturbances of
      motor abilities and delayed speech development. In the present study, we
      therefore investigated whether Nkx2.1 is still expressed in the young adult and
      aged mouse forebrain. After birth, the most intense immunolabeling for Nkx2.1 was
      detected in several components of the hypothalamic region, in the subventricular
      zone of the ventral tips lining the lateral ventricles, and in neighboring
      structures including the striatum, the globus pallidus and the various nuclei of
      the septal complex. Surprisingly, this staining pattern was substantially
      maintained into adulthood. Double immunocytochemistry for Nkx2.1 and various
      neuronal markers revealed that mainly parvalbumin-containing GABAergic neurons,
      but also cholinergic neurons, of the ventral forebrain express this protein.
      Moreover, in situ hybridization confirmed that these neurons maintain synthesis
      of Nkx2.1 throughout life. The robust expression of Nkx2.1 by these neurons
      points to a broad functional spectrum within the adult forebrain.

PMID- 19766602
TI  - Follow-up of latency and threshold shifts of auditory brainstem responses after
      single and interrupted acoustic trauma in guinea pig.
AB  - Thresholds of auditory brainstem responses (ABRs) are widely used to estimate the
      level of noise-induced hearing loss or the level of acquired resistance to
      acoustic trauma after repeated exposures, i.e., the "toughening" effect. Less is
      known about ABR latencies and their relation to threshold changes. Guinea pigs
      were exposed to a traumatic pure tone at 5 kHz, 120 dB SPL, as either single (2
      h, 4 h) or repeated (1 h every 48 h, four times) sessions. Thresholds and
      latencies of ABRs were monitored up to 45 days following the acoustic trauma. We
      show that latencies are prolonged in the case of large temporary threshold shifts
      observed in the days following trauma. The latency shift decreases after several
      repeated exposures, then stabilizes, similar to thresholds, suggesting that the
      "toughening" effect also applies to latencies. Permanent latency shift is usually
      very small compared to the permanent threshold shift. This effect could produce a
      recovery in the ability to process auditory information through the precise
      timing of neuronal events. Our study indicates that when estimated at
      suprathreshold stimulation level (70 dB SPL), latency provides complementary
      information to the sole threshold.

PMID- 19766603
TI  - Long-term functional and neurological outcome after simultaneous treatment with
      tissue-plasminogen activator and hyperbaric oxygen in early phase of embolic
      stroke in rats.
AB  - The combination of hyperbaric oxygen therapy (HBO) and recombinant tissue
      plasminogen activator (tPA) is of interest in the treatment of acute ischemic
      stroke with a view to combine positive effects of both strategies. We
      investigated neurological and functional outcome after early treatment with HBO
      additional to tPA in ischemic stroke. Focal cerebral ischemia was induced using
      an embolic stroke model in 87 male Wistar rats. Animals were randomized to
      therapy with tPA+HBO, tPA alone, or control. Menzies score, Beam walk, and the
      Corner test were assessed for a period of 4 weeks following ischemia. Within the
      first 24 h neurological deficits improved in all groups but most pronounced in
      animals treated with tPA+HBO. Thereafter, a deterioration of neurological
      deficits occurred in the tPA+HBO group with significant differences at day 7, 8,
      18, and 24 (P<0.05). Surprisingly, Beam walk and Corner test results did not
      differ significantly between all groups. This first report of early simultaneous
      treatment with tPA and HBO in experimental embolic stroke with 4-week follow-up
      confirms previous studies reporting positive effects of HBO shortly after the
      ischemia. Following the acute phase, combined tPA and HBO resulted in
      deterioration of neurological deficits without affecting functional recovery.
      Future studies should focus on interactions of tPA and HBO on molecular level
      leading to delayed damage to brain tissue at risk.

PMID- 19766604
TI  - Increase of Kv3.1b expression in avian auditory brainstem neurons correlates with
      synaptogenesis in vivo and in vitro.
AB  - In the auditory system voltage-activated currents mediated by potassium channels
      Kv1.1 and Kv3.1b and their interaction with sodium inward currents play a crucial
      role for computational function. However, it is unresolved how these potassium
      channels are developmentally regulated. We have therefore combined a biochemical
      investigation of Kv1.1 and Kv3.1b protein expression with electrophysiological
      recordings of membrane currents to characterize neuronal differentiation in the
      auditory brain stem of the chick. Differentiation in vitro was compared with
      cells prepared from corresponding embryonic stages in vivo. Using a computer
      model based on the empirical data we were then able to predict physiological
      properties of developing auditory brain stem neurons. In vivo Kv3.1b expression
      increased strongly between E10 and E14, a time of functional synaptogenesis in
      the auditory brainstem. We also found this increase of expression in vitro, again
      coinciding with synaptogenesis in the cultures. Whole-cell patch recordings
      revealed a corresponding increase of the (Kv3.1-like) high threshold potassium
      current. In contrast, Kv1.1 protein expression failed to increase in vitro, and
      changes in (Kv1.1-like) low threshold potassium current with time in culture were
      not significant. Electrophysiological recordings revealed that sodium inward
      currents increased with cultivation time. Thus, our data suggest that Kv3.1b
      expression occurs with the onset of functional synaptogenesis, while a different
      signal, absent from cultures of dissociated auditory brain stem, is needed for
      Kv1.1 expression. A biophysical model constructed with parameters from our
      recordings was used to investigate the functional impact of the currents mediated
      by these channels. We found that during development both high and low threshold
      potassium currents need to be increased in a concerted manner with the sodium
      conductance for the neurons to exhibit fast and phasic action potential firing
      and a narrow time window of coincidence detection.

PMID- 19766605
TI  - Valproate reversibly reduces neurite outgrowth by human SY5Y neuroblastoma cells.
AB  - Valproate (VPA) is a commonly prescribed mood stabilizer. However, emerging
      evidence indicates that VPA administration may cause reversible symptoms of
      Parkinsonism and cognitive decline (P/CD) in some manic patients. The mechanism
      of this phenomenon is unknown. In this study, we used human SY5Y neuroblastoma
      cells as a neuronal model to investigate the effects of VPA on neurite outgrowth
      and neurofilament expression. Data showed that the treatment with VPA at
      therapeutic plasma levels (0.5 mM) significantly reduced cell proliferation from
      day 4 through day 6, and neurite outgrowth length from day 1 through day 6.
      Conversely, VPA had no effect on cell proliferation of human CCF astrocytoma
      cells but stimulated nerve growth factor (NGF)-induced neurite outgrowth from rat
      PC12 pheochromocytoma cells. In parallel to these alterations in human SY5Y
      cells, both mRNA and protein levels of neurofilament 160 (NF160) were
      significantly reduced, starting at day 2 and day 3, respectively, by the
      treatment. The inhibition of neurite outgrowth by VPA was completely reversed 2
      days after cessation of VPA exposure. Furthermore, NF160 protein levels also
      rebounded to control levels after VPA removal. NGF application significantly
      alleviated the inhibition of neurite outgrowth by VPA. These data suggest that
      VPA-modulated NF160 expression was involved in the inhibition and the reversal of
      neurite outgrowth in human neuronal cells.

PMID- 19766606
TI  - Activation of the NMDA receptor involved in the alleviating after-effect of
      repeated stimulation of the subthalamic nucleus on motor deficits in
      hemiparkinsonian rats.
AB  - To test the hypothesis that the cellular mechanism whereby chronic deep brain
      stimulation of the subthalamic nucleus (STN-DBS) induces the improvement of motor
      deficits lasting after stimulation in the hemiparkinsonian (hemi-PD) rat involves
      the NMDA receptor-dependent processes in neurons receiving afferents from the
      STN, we examined whether the NMDA receptor antagonist prevents the alleviating
      after-effect of repeated STN-DBS on motor deficits in hemi-PD. The cylinder test
      was performed before and after repeated STN-DBS over 3 days in hemi-PD that
      received a unilateral injection of 6-OHDA into the medial forebrain bundle 3
      weeks prior to STN-DBS experiments. No significant improvement in the reduced
      frequency of forelimb use and forelimb-use asymmetry was seen in the cylinder
      test after the single STN-DBS, while, when the STN-DBS was applied three times at
      intervals of 24 h, the improvement became apparent and significant only in the
      reduced frequency of forelimb use (akinesia) after termination of the
      stimulation, suggesting the alleviating after-effect of chronic stimulation.
      Then, the effects of intraperitoneal administration of the non-competitive NMDA
      receptor antagonist MK-801 and the competitive NMDA receptor antagonist CPP on
      the alleviating after-effect of the STN-DBS were examined in cylinder tests
      performed before and after repeated STN-DBS for 3 days in hemi-PD. Both MK-801
      (0.1 mg/kg) and CPP (0.5 mg/kg) completely prevented the improvement of the
      akinetic motor deficit after repeated STN-DBS. These results support the
      hypothesis that activation of the NMDA receptor and subsequent cellular processes
      in neurons receiving the afferents from the STN may involve in the mechanism
      underlying the alleviating after-effect of chronic STN-DBS on the akinetic motor
      deficit in hemi-PD.

PMID- 19766608
TI  - Acute systemic blockade of D2 receptors does not accelerate the extinction of
      cocaine-associated place preference.
AB  - Facilitation of extinction can be used as a therapeutic tool in treatment of both
      post-traumatic stress disorder and drug addiction. The present study examined
      whether the blockade of D2 receptors before each extinction trial would
      accelerate the extinction of cocaine-induced place preference. Male Wistar rats
      were initially conditioned and tested for a cocaine-associated place-preference
      (20 mg/kg). On the following day after the initial test, the animals were
      submitted to extinction training. This training consisted of daily sessions in
      which the subjects were alternatively confined during 30 min in the saline and
      cocaine-associated environment. However, 30 min before each extinction trial the
      animals received a systemic injection of D2 antagonist sulpiride. While one group
      was treated with a dose of 50 mg/kg (ip), the other group was treated with a dose
      of 100 mg/kg. An additional control group received injections of saline during
      extinction trials. Twenty-four hours after the last extinction trial, the animals
      were tested again for their preferences to cocaine and saline associated
      environments. Since one round of extinction trial was not sufficient to produce
      extinction of cocaine associated place preference, the animals were submitted to
      a second cycle of extinction trials and test. The systemic administration of the
      two doses of sulpiride (50 and 100 mg/kg) 30 min before each conditioning did not
      enhance the extinction of cocaine-associated place preference. This finding
      suggests that the D2 receptors are not involved in a acute protocol of extinction
      of cocaine-induced place preference.

PMID- 19766607
TI  - Oxytocin modulates unconditioned fear response in lactating dams: an fMRI study.
AB  - Oxytocinergic neurotransmission during lactation contributes to reduction of
      anxiety levels and fear. However, our knowledge of where oxytocin acts in the
      brain to achieve this effect, particularly to an unconditioned fear stimulus, is
      incomplete. We used blood oxygenation level dependent (BOLD) fMRI to test whether
      central administration of oxytocin 45-60 min before fMRI scanning alters maternal
      brain activation in response to a predator scent (TMT, trimethylthiazoline).
      Comparison behavioral experiments that examined maternal responses to this
      unconditioned fear-inducing odor were carried out in a separate cohort of
      lactating rats given similar treatments. Behavioral experiments confirmed the
      effectiveness of oxytocin at reducing freezing behavior as compared to vehicle
      controls. Our fMRI findings indicate that oxytocin modulated both positive and
      negative BOLD responses across several olfactory and forebrain nuclei.
      Significantly greater percent increases in BOLD signal in response to TMT were
      observed in the anterior cingulate, bed nucleus of stria terminalis and
      perirhinal area of oxytocin pretreated rats. These animals also showed
      significantly larger percent decreases in BOLD in mammillary bodies, secondary
      motor cortex, gustatory cortex, prelimbic prefrontal cortex, orbital cortex, and
      the anterior olfactory nucleus. The observed pattern of brain activity suggests
      that oxytocin enhances neural processing in emotion and cognition driven brain
      areas such as the cingulate cortex, while dramatically reducing activity in areas
      also controlling autonomic, visceromotor and skeletomotor responses. The present
      data contribute to the growing literature suggesting the oxytocin modulate the
      integration of emotional and cognitive information through myriad brain regions
      to facilitate decreases in anxiety (even to an unconditioned stimulus) while
      potentially promoting pair-bonding, social memory and parental care.

PMID- 19766609
TI  - Pitch discrimination in cerebellar patients: evidence for a sensory deficit.
AB  - In the last two decades, a growing body of research showing cerebellar
      involvement in an increasing number of nonmotor tasks and systems has prompted an
      expansion of speculations concerning the function of the cerebellum. Here, we
      tested the predictions of a hypothesis positing cerebellar involvement in sensory
      data acquisition. Specifically, we examined the effect of global cerebellar
      degeneration on primary auditory sensory function by means of a pitch
      discrimination task. The just noticeable difference in pitch between two tones
      was measured in 15 healthy controls and in 15 high functioning patients afflicted
      with varying degrees of global cerebellar degeneration caused by hereditary,
      idiopathic, paraneoplastic, or postinfectious pancerebellitis. Participants also
      performed an auditory detection task assessing sustained attention, a test of
      verbal auditory working memory, and an audiometric test. Patient pitch
      discrimination thresholds were on average five and a half times those of controls
      and were proportional to the degree of cerebellar ataxia assessed independently.
      Patients and controls showed normal hearing thresholds and similar performance in
      control tasks in sustained attention and verbal auditory working memory. These
      results suggest there is an effect of cerebellar degeneration on primary auditory
      function. The findings are consistent with other recent demonstrations of
      cerebellar-related sensory impairments, and with robust cerebellar auditorily
      evoked activity, confirmed by quantitative meta-analysis, across a range of
      functional neuroimaging studies dissociated from attention, motor, affective, and
      cognitive variables. The data are interpreted in the context of a sensory
      hypothesis of cerebellar function.

PMID- 19766610
TI  - T3 differentially regulates TRH expression in developing hypothalamic neurons in
      vitro.
AB  - Triiodothyronine (T3) plays an important role during development of the central
      nervous system. T3 effects on gene expression are determined in part by the type
      of thyroid hormone receptors (TRs) expressed in a given cell type. Previous
      studies have demonstrated that thyrotropin releasing hormone (TRH) transcription
      in the adult hypothalamus is subjected to negative regulation by thyroid
      hormones. However, the role of T3 on the development of TRH expression is
      unknown. In this study we used primary cultures derived from 17-day-old fetal rat
      hypothalamus to analyze the effects of T3 on TRH gene expression during
      development. T3 increased TRH mRNA expression in immature cultures, but decreased
      it in mature cultures. In addition, T3 up-regulated TRalpha1 and TRbeta2 mRNA
      expression. TRalpha1 expression coincided chronologically with that of TRH in the
      rat hypothalamus in vivo. Maturation of TRH expression in the hypothalamus may
      involve T3 acting through TRalpha1.

PMID- 19766611
TI  - Thyrotropin-releasing hormone d,l polylactide nanoparticles (TRH-NPs) protect
      against glutamate toxicity in vitro and kindling development in vivo.
AB  - Thyrotropin-releasing hormone (TRH) is reported to have anticonvulsant effects in
      animal seizure models and certain intractable epileptic patients. However, its
      duration of action is limited by rapid tissue metabolism and the blood brain
      barrier. Direct nose-brain delivery of neuropeptides in sustained-release
      biodegradable nanoparticles (NPs) is a promising mode of therapy for enhancing
      CNS bioavailability. Bioactivity/neuroprotection of d,l polylactide nanoparticles
      containing TRH was assessed against glutamate toxicity in cultured rat fetal
      hippocampal neurons. Subsequently, we utilized the kindling model of temporal
      lobe epilepsy to determine if intranasal administration of nanoparticles
      containing TRH (TRH-NPs) could inhibit kindling development. Animals received
      daily treatments of either blank (control) or TRH-NPs for 7 days before
      initiation of kindling. On day 8 and each day thereafter until either fully
      kindled or until day 20, the animals received daily treatments before receiving a
      kindling stimulus 3 h later. Afterdischarge duration (ADD) was assessed via
      electroencephalographs recorded from electrodes in the basolateral amygdalae and
      behavioral seizure stereotypy was simultaneously recorded digitally. Intranasal
      application of TRH-NPs resulted in a significant reduction in seizure ADD as
      kindling progressed, while the number of stimulations required to reach stage V
      seizures and to become permanently kindled was significantly greater in TRH-NP
      treated subjects. Additionally, delay to clonus was significantly prolonged while
      clonus duration was reduced indicating a less severe seizure in TRH-NP-treated
      subjects. Our results provide proof of principle that intranasal delivery of
      sustained-release TRH-NPs may be neuroprotective and can be utilized to suppress
      seizures and perhaps epileptogenesis.

PMID- 19766612
TI  - Anterograde labeling of ventrolateral funiculus pathways with spinal enlargement
      connections in the adult rat spinal cord.
AB  - The ventrolateral funiculus in the spinal cord has been identified as containing
      important ascending and descending pathways related to locomotion and interlimb
      coordination. The purpose of this descriptive study was to investigate the
      patterns of axon termination of long ascending and descending ventrolateral
      pathways within the cervical and lumbar enlargements of the adult rat spinal
      cord. To accomplish this, we made discrete unilateral injections of the tracer
      biotinylated dextran-amine (BDA) into the ventrolateral white matter at T9.
      Although some BDA-labeled axons with varicosities were found bilaterally at all
      cervical levels, particularly dense BDA labeling was observed in laminae VIII and
      IX ipsilaterally at the C6 and C8 levels. In the same animals, dense terminal
      labeling was found in the lumbar enlargement in medial lamina VII and
      ventromedial laminae VIII and IX contralaterally. This labeling was most apparent
      in the more rostral lumbar segments. These observations continue the
      characterization of inter-enlargement (long propriospinal) pathways, illustrating
      a substantial and largely reciprocal inter-enlargement network with large numbers
      of both ascending and descending ventrolateral commissural neurons. These
      pathways are anatomically well-suited to the task of interlimb coordination and
      to participate in the remarkable recovery of locomotor function seen in the rat
      following thoracic spinal cord injuries that spare as little as 20% of the total
      white matter cross sectional area.

PMID- 19766613
TI  - Metabolic activation of phenanthrene by human and mouse cytochromes P450 and
      pharmacokinetics in CYP1A2 knockout mice.
AB  - In the present study V79 Chinese hamster cells were genetically engineered for
      stable expression of the cytochromes P450 1A1, 1A2, 1B1, and 2E1 from man and
      mouse to investigate species-specific differences in the regioselective
      metabolism and toxicity of phenanthrene (Phe), the simplest polycyclic aromatic
      hydrocarbon (PAH) forming a bay-region. Phe is present in various environmental
      samples and serves as a model substrate for PAH exposure in human biomonitoring
      studies. For this reason we explored metabolite profiles and metabolite-dependent
      cytotoxic activities in vitro. The total turnover of CYP-mediated transformation
      of Phe was as follows: human CYP1B1>CYP1A1>CYP1A2>>CYP2E1, and for mouse
      CYP1A2>>CYP2E1>CYP1A1. Striking species differences were seen as mouse CYP1B1 did
      not activate Phe at all, but human CYP1B1 exhibited a significant metabolic
      turnover comparable to CYP1A1 and CYP1A2. In vivo studies monitoring the whole
      blood Phe elimination in CYP1A2 knockout and wild-type mice after oral
      administration confirmed involvement of CYP1A2 in the bioactivation of Phe, but
      other processes must contribute also. Our data suggest that in humans not only
      CYP1A2 expressed solely in the liver plays a crucial role in Phe metabolism, but
      also constitutively expressed extrahepatic CYP1B1 in tissues such as lung, kidney
      or intestine. This finding will substantially improve the validity of human
      biomonitoring studies using individual Phe metabolites for the assessment of PAH
      exposure.

PMID- 19766614
TI  - A novel insertion mutation in the SEDL gene results in X-linked
      spondyloepiphyseal dysplasia tarda in a large Chinese pedigree.
AB  - BACKGROUND: Spondyloepiphyseal dysplasia tarda (SEDT) is an X-chromosome linked
      primary skeletal dysplasia characterized by a disproportionate short-trunked
      short stature, dysplasia of the large joints and flattened thoracic and lumber
      vertebral bodies. The objective of this study is to describe a large Chinese SEDT
      family with a milder phenotype and describe the molecular and clinical findings.
      METHODS: Eight affected males of the family were diagnosed with SEDT according to
      their clinical and radiological features. Direct DNA sequencing of the SEDL gene
      was performed. RT-PCR experiments on total RNA from blood lymphocytes were
      performed to confirm the defect on the SEDL gene. A short summary of all
      currently known SEDL gene mutations is presented. RESULTS: DNA sequencing
      revealed that all the affected males carried an insertion mutation (c.370
      371insA) unreported previously, predicted to result in frameshifts and generate a
      premature stop codon (p.S124fsX127). The identical mutation was also observed in
      a 10-year old presymptomatic boy of the family. Eight female carriers had the
      typical sequencing chromatograms of heterozygotes. CONCLUSIONS: Identification of
      the novel insertion mutation (c.370-371insA) in this SEDT family enables carrier
      detection and presymptomatic/prenatal diagnosis, but also the detailed molecular
      and clinical features will be useful for extending the evidence for genetic and
      phenotypic heterogeneity in SEDT.

PMID- 19766615
TI  - Measurement uncertainty of eGFR at low creatinine levels: be careful to not
      overestimate.

PMID- 19766616
TI  - Armand M. Karow, Jr.: Looking back.
AB  - Armand Karow, Jr. was a devoted scholar of cryobiology who was responsible for
      the creation of landmark books and many unique observations. Driven into
      cryobiology by a fascination with organ cryopreservation that dated from his high
      school days, Karow carried out or contributed to research on the cryopreservation
      of hearts, kidneys, pancreatic islets, and reproductive cells and tissues. His
      interests included not only conventional issues in cryobiology such as
      cryoprotectant permeation kinetics, theories of freezing injury in cells and
      tissues, and electromagnetic warming of large organs, but also more esoteric
      questions such as the limits of tolerance of mammalian organs to high pressures,
      the role of molecular hydration in cell viability, the pharmacological effects of
      cryoprotectants (which he frequently referred to as drugs), the limits of
      cryoprotectant tolerance at higher temperatures, and low temperature
      pharmacology. A look back at some of the discoveries made by Karow and his
      colleagues reveals many interesting leads whose further investigation could
      continue to provide valuable new insights in the future.

PMID- 19766617
TI  - Effect of cryopreservation on IL-4, IFNgamma and IL-6 production of porcine
      peripheral blood lymphocytes.
AB  - Cryopreservation of animal or human peripheral blood mononuclear cells (PBMC) is
      a commonly used technique. Effects of cryopreservation on functional capacity,
      especially the cytokine production of human PBMCs, have been extensively defined.
      However, certain animals, such as livestock, are a shortage of these information.
      Here we investigated the effects of cryopreservation on cytokine (IL-4, IFNgamma
      and IL-6) production of porcine PBMC. The porcine PBMCs were cryopreserved at 
      196 degrees C for a variety time periods for 2, 5, 25 and 50 days. Viability and
      cytokine production of the porcine PBMCs were measured before and after
      cryopreservation. The results showed that about 90% cell recovery rate was
      obtained at each storage time, indicating that about 10% loss of PBMCs in this
      short-term cryopreservation was due to the freezing process rather than the
      duration of cryopreservation. The fresh or frozen resting porcine PBMCs produced
      little cytokines in the absence of stimulation. However, three cytokines were
      apparently increased after PMA stimulation in both fresh and frozen porcine
      PBMCs. The sensitivity of frozen cells to PMA simulation for IFNgamma and IL-6
      production was different from that of the fresh ones. IFNgamma production from
      the frozen PBMCs was significantly higher than that from the fresh ones (P<0.01).
      In contrast, IL-6 level from the frozen sample was significantly lower than that
      from the fresh one (P<0.05). Those results indicate that cryopreservation can
      increase the sensitivity of porcine PBMCs stimulated by PMA for IFNgamma
      production but not for IL-6 production. There was no significant difference of IL
      4 production between fresh and frozen cells either stimulated (P>0.05) or un
      stimulated (P>0.05).

PMID- 19766618
TI  - Immunomagnetic bead separation of mononuclear cells from contaminating
      granulocytes in cryopreserved blood samples.
AB  - Density gradient centrifugation usually allows efficient separation of
      mononuclear cells from granulocytes using fresh human blood samples. However, we
      have found that with cryopreserved blood samples, density gradient centrifugation
      fails to separate granulocytes from mononuclear cells and have explored using
      immunomagnetic anti-CD15 microbeads as an alternate method to separate these cell
      populations. Using cryopreserved blood samples from 10 healthy donors we have
      shown that granulocytes express a significantly higher level of CD15 antigen than
      monocytes and lymphocytes, which allows for their efficient separation from
      mononuclear cells using anti-CD15 microbeads. This procedure is critical for
      purification of individual cell populations from cryopreserved leukocyte samples
      and could also potentially be applied to avoid granulocyte contamination of
      mononuclear cells isolated from stored blood and from patients with sepsis or
      thermal injury.

PMID- 19766619
TI  - Characterization of cryobiological responses in TF-1 cells using interrupted
      freezing procedures.
AB  - Cryopreservation currently is the only method for long-term preservation of
      cellular viability and function for uses in cellular therapies. Characterizing
      the cryobiological response of a cell type is essential in the approach to
      designing and optimizing cryopreservation protocols. For cells used in therapies,
      there is significant interest in designing cryopreservation protocols that do not
      rely on dimethyl sulfoxide (Me(2)SO) as a cryoprotectant, since this
      cryoprotectant has been shown to have adverse effects on hematopoietic stem cell
      (HSC) transplant patients. This study characterized the cryobiological responses
      of the human erythroleukemic stem cell line TF-1, as a model for HSC. We measured
      the osmotic parameters of TF-1 cells, including the osmotically-inactive
      fraction, temperature-dependent membrane hydraulic conductivity and the membrane
      permeability to 1M Me(2)SO. A two-step freezing procedure (interrupted rapid
      cooling with hold time) and a graded freezing procedure (interrupted slow cooling
      without hold time) were used to characterize TF-1 cell recovery during various
      phases of the cooling process. One outcome of these experiments was high recovery
      of TF-1 cells cryopreserved in the absence of traditional cryoprotectants. The
      results of this study of the cryobiology of TF-1 cells will be critical for
      future understanding of the cryobiology of HSC, and to the design of
      cryopreservation protocols with specific design criteria for applications in
      cellular therapies.

PMID- 19766620
TI  - Essential mesenchymal role of small GTPase Rac1 in interdigital programmed cell
      death during limb development.
AB  - Developing vertebrate limbs are often utilized as a model for studying pattern
      formation and morphogenetic cell death. Herein, we report that conditional
      deletion of Rac1, a member of the Rho family of proteins, in mouse limb bud
      mesenchyme led to skeletal deformities in the autopod and soft tissue syndactyly,
      with the latter caused by a complete absence of interdigital programmed cell
      death. Furthermore, the lack of interdigital programmed cell death and associated
      syndactyly was related to down-regulated gene expression of Bmp2, Bmp7, Msx1, and
      Msx2, which are known to promote apoptosis in the interdigital mesenchyme. Our
      findings from Rac1 conditional mutants indicate crucial roles for Rac1 in limb
      bud morphogenesis, especially interdigital programmed cell death.

PMID- 19766621
TI  - Complex interactions amongst N-cadherin, DLAR, and Liprin-alpha regulate
      Drosophila photoreceptor axon targeting.
AB  - The formation of stable adhesive contacts between pre- and post-synaptic neurons
      represents the initial step in synapse assembly. The cell adhesion molecule N
      cadherin, the receptor tyrosine phosphatase DLAR, and the scaffolding molecule
      Liprin-alpha play critical, evolutionarily conserved roles in this process.
      However, how these proteins signal to the growth cone and are themselves
      regulated remains poorly understood. Using Drosophila photoreceptors (R cells) as
      a model, we evaluate genetic and physical interactions among these three
      proteins. We demonstrate that DLAR function in this context is independent of
      phosphatase activity but requires interactions mediated by its intracellular
      domain. Genetic studies reveal both positive and, surprisingly, inhibitory
      interactions amongst all three genes. These observations are corroborated by
      biochemical studies demonstrating that DLAR physically associates via its
      phosphatase domain with N-cadherin in Drosophila embryos. Together, these data
      demonstrate that N-cadherin, DLAR, and Liprin-alpha function in a complex to
      regulate adhesive interactions between pre- and post-synaptic cells and provide a
      novel mechanism for controlling the activity of Liprin-alpha in the developing
      growth cone.

PMID- 19766622
TI  - Cell death and tissue remodeling in planarian regeneration.
AB  - Many long-lived organisms, including humans, can regenerate some adult tissues
      lost to physical injury or disease. Much of the previous research on mechanisms
      of regeneration has focused on adult stem cells, which give rise to new tissue
      necessary for the replacement of missing body parts. Here we report that
      apoptosis of differentiated cells complements stem cell division during
      regeneration in the planarian Schmidtea mediterranea. Specifically, we developed
      a whole-mount TUNEL assay that allowed us to document two dramatic increases in
      the rate of apoptosis following amputation-an initial localized response near the
      wound site and a subsequent systemic response that varies in magnitude depending
      on the type of fragment examined. The latter cell death response can be induced
      in uninjured organs, occurs in the absence of planarian stem cells, and can also
      be triggered by prolonged starvation. Taken together, our results implicate
      apoptosis in the restoration of proper anatomical scale and proportion through
      remodeling of existing tissues. We also report results from initial mechanistic
      studies of apoptosis in planarians, which revealed that a S. mediterranea homolog
      of the antiapoptotic gene BCL2 is required for cell survival in adult animals. We
      propose that apoptosis is a central mechanism working in concert with stem cell
      division to restore anatomical form and function during metazoan regeneration.

PMID- 19766623
TI  - Flexibility of transcription factor target site position in conserved cis
      regulatory modules.
AB  - Eight Strongylocentrotus purpuratus cis-regulatory modules, in each of which up
      to three different transcription factor target sites had been previously
      authenticated in gene transfer and mutagenesis studies, were compared to the
      orthologous modules in the genome of Lytechinus variegatus. These species
      diverged about 50 million years ago. The orthologous modules were identified in
      sequenced Lytechinus BACs, as conserved sequence patches in similar regions of
      the respective genes. The similar functionality of several of these control
      modules in the two species was confirmed by cross-species gene transfer
      experiments. In each case the repertoire of transcription factor target sites was
      the same in the orthologous modules, but the positions of the individual sites
      with respect to one another was evolutionarily flexible, even though the
      intervening sequence was often strongly conserved. The most invariably conserved
      features, as seen also in other systems, were pairs of target sites that are
      immediately adjacent to one another. Their conservation is probably due to the
      necessity for interaction of proximally bound transcription factors, while a
      facilitated form of sequence conversion might be the mechanism of site position
      change.

PMID- 19766624
TI  - PPARdelta ligand L-165041 ameliorates Western diet-induced hepatic lipid
      accumulation and inflammation in LDLR-/- mice.
AB  - Although peroxisome proliferator-activated receptor delta (PPARdelta) has been
      implicated in energy metabolism and lipid oxidation process, detailed roles of
      PPARdelta in lipid homeostasis under pathologic conditions still remain
      controversial. Thus, we investigated the effect of PPARdelta ligand L-165041 on
      Western diet-induced fatty liver using low-density lipoprotein receptor-deficient
      (LDLR(-/-)) mice. LDLR(-/-) mice received either L-165041 (5mg/kg/day) or vehicle
      (0.1N NaOH) with Western diet for 16 weeks. According to our data, L-165041
      drastically reduced lipid accumulation in the liver, decreasing total hepatic
      cholesterol and triglyceride content compared to the vehicle group. Gene
      expression analysis demonstrated that L-165041 lowered hepatic expression of
      PPARgamma, apolipoprotein B, interleukin 1 beta (IL-1beta), and interleukin-6. In
      contrast, L-165041 increased hepatic expressions of PPARdelta, lipoprotein lipase
      (LPL), and ATP-binding cassette transporter G1 (ABCG1). Our data suggest that L
      165041 might be effective in preventing Western diet-induced hepatic steatosis by
      regulating genes involved in lipid metabolism and the inflammatory response.

PMID- 19766625
TI  - Anti-inflammatory effects of phosphatidylcholine in neutrophil leukocyte
      dependent acute arthritis in rats.
AB  - We investigated the effects of exogenous phosphatidylcholine (PC) and non
      steroidal diclofenac supplementation on polymorphonuclear cell influx in
      carrageenan-induced arthritis in rats. The microcirculatory consequences were
      evaluated by a novel method developed for direct intravital microscopic
      observation of the synovial membrane. Arthritis was induced by injection of a
      mixture of 2% lambda-carrageenan and 4% kaolin into the knee joints and the
      animals were treated orally with PC (150 mg/kg twice daily), sodium diclofenac
      (0.5mg/kg twice daily) or saline vehicle. Intravital videomicroscopy was used to
      investigate the leukocyte-endothelial interactions directly in the synovial
      membrane at 6h after the challenge. The inflammation-induced thermal and
      mechanical secondary hyperalgesic reactions were assessed at 24h, and the knee
      volume changes at 48h after the insult. The development of arthritis was
      accompanied by a significant increase in the number of adherent leukocytes in the
      synovial postcapillary venules, but this increase was reduced significantly (by
      approximately 40%) by PC, and slightly (by 22%) by diclofenac treatment. The
      perivascular infiltration of the neutrophil leukocytes and the intercellular
      adhesion molecule-1 (ICAM-1) expressions were reduced only by PC treatment. The
      significant decrease (45%) in the thermal nociceptive latency, the 3-fold
      increase in the mechanical touch sensitivity and the knee cross-sectional area
      (which was increased by 35% by the arthritis induction) were significantly
      ameliorated by both treatments. The present study demonstrated the anti
      inflammatory effects of PC in experimental arthritis. The therapeutic potential
      may be linked to the reduction of neutrophil leukocyte-mediated microcirculatory
      inflammatory reactions.

PMID- 19766626
TI  - BS69 undergoes SUMO modification and plays an inhibitory role in muscle and
      neuronal differentiation.
AB  - BS69, an adenovirus E1A binding protein, has been described as a co-repressor in
      association with various transcription factors. But its characteristics and exact
      biological functions remain largely unknown at present. Now we intensively
      investigated the localization of BS69 and its various truncated derivatives and
      found that: (a) BS69 forms oligomer through its C-terminus and (b) both PHD and
      MYND domain are important for the localization of BS69. Furthermore, we provided
      evidence showing that BS69 interacts with PIAS1 (a well-characterized SUMO E3
      enzyme) and Ubc9 (the only SUMO E2 enzyme so far identified) through its distinct
      regions. And PIAS1 significantly increases the SUMO modification of BS69. More
      importantly, in terms of the biological function of BS69, we found that BS69
      plays an inhibitory role in the muscle and neuronal differentiation process. By
      taking advantage of several PHD and MYND domain mutants of BS69, we found that
      the PHD domain plays indispensable roles in the localization, sumoylation and
      function of BS69. Thus, our work contributed to the more intensive understanding
      of BS69.

PMID- 19766627
TI  - Apoptosis signal-regulating kinase (ASK)-1 mediates apoptosis through activation
      of JNK1 following engagement of membrane immunoglobulin.
AB  - Engagement of membrane immunoglobulin (mIg) on WEHI-231 mouse B lymphoma cells
      results in growth arrest at the G1 phase of the cell cycle, followed by a
      reduction of mitochondrial membrane potential (DeltaPsim) and apoptosis. WEHI-231
      cells resemble immature B cells in terms of the cell surface phenotype and
      sensitivity to mIg engagement. However, the molecular mechanisms underlying mIg
      induced loss of DeltaPsim and apoptosis have not yet been established. In this
      study, we show that apoptosis signal-regulating kinase 1 (ASK1)-c-Jun N-terminal
      kinase 1 (JNK1) signaling pathway participates in mIg-induced apoptosis through
      the generation of reactive oxygen species (ROS). Stimulation of WEHI-231 cells
      with anti-IgM induces phosphorylation and subsequent activation of ASK1, leading
      to JNK activation. Anti-IgM stimulation immediately (5 min) induces hydrogen
      peroxide (H2O2) production with a substantial increase during later time points
      (36-48 h), accompanied by loss of DeltaPsim and an increase in cells with sub-G1
      DNA content. The anti-IgM-induced late-phase H2O2 production, loss of DeltaPsim,
      and increase in the sub-G1 fraction were all reduced substantially in WEHI-231
      cells overexpressing a dominant-negative form of ASK1, compared with control
      vector alone, but enhanced substantially in cells overexpressing a constitutively
      active form of ASK1. These mIg-mediated events were also partially abrogated by
      ROS scavenger N-acetyl-L-cysteine (NAC). Taken together, these results suggest
      that mIg engagement induces H2O2 production leading to activation of ASK1-JNK1
      pathway, creating a feedback amplification loop of ROS-ASK/JNK that leads to loss
      of DeltaPsim and finally apoptosis.

PMID- 19766628
TI  - Chemically distinct HDAC inhibitors prevent adipose conversion of subcutaneous
      human white preadipocytes at an early stage of the differentiation program.
AB  - The present study investigated the effect of HDAC inhibitors on the
      differentiation of human subcutaneous white adipocytes. Results showed that
      trichostatin A, suberoylanilide hydroxamic acid, valproic acid and MS-275
      inhibited triglyceride accumulation, GPDH activity and FABP4 protein expression
      in adipocytes, as well as leptin and VEGF release, while cells retained a
      fibroblast-like morphology. HDAC inhibitors exerted their antiadipogenic effect
      without inducing apoptosis or affecting cell viability and number, while 1-2 log
      unit higher concentrations were mostly required to exert an antiproliferative
      effect or to reduce LDH activity. A brief exposure to HDAC inhibitors at the
      beginning of the differentiation program was sufficient to observe the
      antiadipogenic effect while differentiation restarted after compound withdrawal
      and further exposure to inducers of differentiation demonstrating reversibility
      of the events. HDAC inhibitors hyperacetylated histone H4, but only hydroxamate
      based compounds produced a massive acetylation of alpha-tubulin, indicating that
      this latter event is not required to prevent adipose conversion. HDAC inhibitors
      induced a significant reduction of the expression of the transcription factor
      C/EBPalpha, an early marker of differentiation, and a diminution of fibronectin
      immunoreactivity was also observed. In conclusion, HDAC inhibitors from different
      chemical classes potently inhibited human adipose conversion at an early stage of
      the differentiation program.

PMID- 19766629
TI  - A nonsense mutation in Gnat1, encoding the alpha subunit of rod transducin, in
      spontaneous mouse models of retinal dysfunction.
AB  - ICR-derived retinal dysfunction (IRD) 1 and IRD2 mice are new spontaneous mouse
      models of rod-cone and rod dysfunctions, respectively. In this study, we
      investigated the cause of rod dysfunction in IRD1 and IRD2 mice. Gene expression
      of rod phototransduction proteins was analyzed by quantitative real-time RT-PCR.
      mRNA levels of Gnat1, which encodes the alpha subunit of rod transducin
      (Tralpha), were severely reduced. Tralpha protein was immunohistochemically
      undetectable in both IRD1 and IRD2 mice. Sequencing of Tralpha cDNA revealed a 48
      base pair (bp) insertion between exons 4 and 5 in both mutant strains. The
      insertion changed codon 150 (TAC) to a stop codon (TAG) (Tyr150Ter). The
      truncated Tralpha protein was undetectable in the retinas of both mutants by
      western blot analysis using a primary antibody against the N-terminal region. A
      57-bp deletion was identified in intron 4 of the Gnat1 gene, which encodes the
      Tralpha protein, and included the last two bases of the splice donor site of
      intron 4. Thus our results showed that IRD1 and IRD2 mice harbor a nonsense
      mutation in the Gnat1 gene, resulting in the absence or suppressed expression of
      the Tralpha protein, which is the likely cause of rod dysfunction in both
      mutants.

PMID- 19766630
TI  - Prevention of experimental autoimmune uveoretinitis by blockade of osteopontin
      with small interfering RNA.
AB  - Osteopontin (OPN) is elevated during the progression of experimental autoimmune
      uveoretinitis (EAU) in C57BL/6 (B6) mice. Furthermore, EAU symptoms are
      ameliorated in OPN knockout mice or in B6 mice treated with anti-OPN antibody
      (M5). Recently, OPN has been shown to promote the Th1 response not only in the
      extracellular space as a secretory protein but also in cytosol as a signaling
      component. Thus, we attempted to reduce OPN in both compartments by using a small
      interfering RNA (siRNA) targeting the OPN coding sequence (OPN-siRNA). EAU was
      induced in B6 mice by immunization with human interphotoreceptor retinoid-binding
      protein (hIRBP) peptide sequence 1-20. The OPN- or control-siRNA was administered
      with hydrodynamic methods 24 h before and simultaneously with immunization
      (prevention regimen). When plasma OPN levels were quantified following siRNA
      administration with the prevention regimen, the level in the OPN-siRNA-treated
      group was significantly lower than that in the control-siRNA-treated group.
      Accordingly, the clinical and histopathological scores of EAU were significantly
      reduced in B6 mice when siRNA caused OPN blockade. Furthermore, TNF-alpha, IFN
      gamma, IL-2, GM-CSF and IL-17 levels in the culture supernatants were markedly
      suppressed in the OPN-siRNA-treated group, whereas the proliferative responses of
      T lymphocytes from regional lymph nodes against immunogenic peptides was not
      significantly reduced. On the other hand, the protection was not significant if
      the mice received the OPN-siRNA treatment on day 7 and day 8 after immunization
      when the clinical symptoms appeared overt (reversal regimen). Our results suggest
      that OPN blockade with OPN-siRNA can be an alternative choice for the usage of
      anti-OPN antibody and controlling uveoretinitis in the preventive regimen.

PMID- 19766631
TI  - COUP-TFI and -TFII nuclear receptors are expressed in amacrine cells and play
      roles in regulating the differentiation of retinal progenitor cells.
AB  - Chicken ovalbumin upstream promoter transcription factors (COUP-TFs) are members
      of the steroid/thyroid hormone receptor superfamily. We have shown that two
      homologous COUP-TF genes, COUP-TFI and COUP-TFII, are expressed in developing
      mouse retina with a unique gradient along the dorsal-ventral axis. In this work,
      we aimed to characterize the detailed expression patterns of COUP-TFs in mature
      retina. Their functions in retinal progenitor cell differentiation into subtypes
      of mature retinal cells were also examined. Immunostaining of frozen mouse
      retinal sections with antibodies against COUP-TFs and markers for retinal
      subtypes revealed that COUP-TFI and -TFII are expressed in amacrine cells,
      especially in a glycinergic subtype in mature mouse retina. Forced expression of
      COUP-TFI and -TFII in mouse retinal explant culture by retrovirus-mediated gene
      transfer promoted amacrine and cone photoreceptor cell differentiation, whereas
      that of rod photoreceptors decreased. Cell proliferation and apoptosis were not
      affected by the perturbation of COUP-TFI and -TFII expression levels. Using the
      Y79 retinoblastoma cell line, we observed that COUP-TFI and -TFII suppressed the
      transcriptional activation of the Nrl gene. We then analyzed one another member
      of COUP-TF transcription factors, COUP-TFgamma, whose structure is relatively
      distant from those of COUP-TFI and -TFII. It is expressed mainly in horizontal
      cells and has weak activity in inducing amacrine cells when COUP-TFgamma was
      ectopically expressed in retinal explants. In summary, we found that COUP-TFI and
      -TFII play roles in amacrine cell differentiation, and COUP-TFgamma has distinct
      expression pattern and roles during retinal development.

PMID- 19766632
TI  - Osmosensitive response of glutamate in the substantia nigra.
AB  - Previous studies have suggested the increase of extracellular glutamate (GLU) in
      the substantia nigra (SN) as a cause of dopamine-cell degeneration
      (excitotoxicity) in Parkinson's disease (PD). However, the mechanisms involved in
      this increase remain unknown. The present work studied osmoregulation as a cause
      of GLU release in the SN. Microdialysis was used to change extracellular
      osmolarity, to administer drugs and to quantify the extracellular non-synaptic
      GLU (EnS-GLU). Two osmolarity modifications were performed, a moderate decrease
      (5%) resembling physiological modifications and a substantial decrease (>or=20%
      decrease) similar to that observed under pathological conditions. Hypo-osmolarity
      induced a dose-response (285-80 mOsm) increase of EnS-GLU which was detected
      after small osmolarity modifications (15 mOsm) and which was very marked (>1000%)
      after more intense osmolarity changes. This response disappeared after pre
      treating rats with a P2 purinergic-receptor antagonist (pyridoxalphosphate-6
      azophenyl-2',4'-disulphonic acid; 1 mM) suggesting ATP involvement in the
      osmosensitive EnS-GLU response. The EnS-GLU increase observed after
      administration of ATP (0.1-100 microM) and 2-methylthioadenosine triphosphate
      tetrasodium (P2-receptor agonist; 100 microM) and the lack of effects of
      adenosine administration (1 mM) suggest that the ATP action on P2 receptors is an
      amplificatory mechanism in the osmosensitive EnS-GLU response. The marked action
      of osmolarity on extracellular Glu suggests osmolarity regulation as a possible
      source for excitotoxicity in the SN.

PMID- 19766633
TI  - Axenization and optimization of in vitro growth of clonal cultures of
      Tetratrichomonas gallinarum and Trichomonas gallinae.
AB  - A rapid and simple procedure was established to obtain clonal axenic cultures of
      Tetratrichomonas gallinarum and Trichomonas gallinae and to optimize their in
      vitro growth conditions. Medium 199 was used for axenization of two genetically
      different clones of T. gallinarum and T. gallinae. Six different media were used
      to optimize the growth behaviour of axenically grown parasites: Medium 199, TYM,
      TYI-S-33, Hollander fluid (HF), Trichomonas vaginalis (TV) and modified TV media.
      The highest cell yields for both axenic clones of T. gallinarum were obtained in
      modified TV medium without antibiotics. The maximum numbers of trophozoites of T.
      gallinae were obtained in an optimized HF medium. This study demonstrated that
      axenic cultures for T. gallinarum and T. gallinae could be obtained avoiding the
      migration technique through a V-tube. Following axenization and optimization,
      both clones of T. gallinarum and T. gallinae could be propagated both aerobically
      and anaerobically.

PMID- 19766634
TI  - Balamuthia mandrillaris: role of galactose in encystment and identification of
      potential inhibitory targets.
AB  - Balamuthia mandrillaris is a causative agent of granulomatous encephalitis that
      almost always proves fatal. A major concern during the course of therapy is that
      B. mandrillaris can transform into cysts. Cysts are highly resistant to physical
      and chemical conditions and present a problem in successful antimicrobial
      chemotherapy. However, the underlying mechanisms of B. mandrillaris
      transformation into cysts are not known. In this study, we examined the effects
      of exogenous sugars on B. mandrillaris encystment. The findings revealed that
      free exogenous galactose, but not other sugars, enhanced parasite differentiation
      into cysts, and apparently a galactose-binding protein is involved in B.
      mandrillaris encystment. Cytoskeletal re-arrangements and phosphatidylinositol 3
      kinase (PI3K)-mediated pathways are involved in B. mandrillaris encystment based
      on inhibitor studies. Dual functionality of galactose-binding protein in B.
      mandrillaris pathogenesis and encystment is discussed further.

PMID- 19766635
TI  - System-level design of bacterial cell cycle control.
AB  - Understanding of the cell cycle control logic in Caulobacter has progressed to
      the point where we now have an integrated view of the operation of an entire
      bacterial cell cycle system functioning as a state machine. Oscillating levels of
      a few temporally-controlled master regulator proteins in a cyclical circuit drive
      cell cycle progression. To a striking degree, the cell cycle regulation is a
      whole cell phenomenon. Phospho-signaling proteins and proteases dynamically
      deployed to specific locations on the cell wall are vital. An essential phospho
      signaling system integral to the cell cycle circuitry is central to accomplishing
      asymmetric cell division.

PMID- 19766636
TI  - Ethylene and cold participate in the regulation of LeCBF1 gene expression in
      postharvest tomato fruits.
AB  - C-repeat/dehydration-responsive element binding factor (CBF) is a transcription
      factor regulating cold response in plants, of which little is known in fruits. We
      showed a double-peak expression pattern of Lycopersicon esculentum putative
      transcriptional activator CBF1 (LeCBF1) in mature green fruit. The peaks appeared
      at 2 and 16 h after subjection to cold storage (2 degrees C). The second peak was
      coincident with, and thus caused by a peak in endogenous ethylene production. We
      showed that LeCBF1 expression was regulated by exogenous ethylene and 1
      methylcyclopropene, and was not expressed without cold induction. LeCBF1
      expression was different in the five maturation stages of fruits, but expression
      peaked at 2 h at all stages.

PMID- 19766637
TI  - Crystal structure of the NEMO ubiquitin-binding domain in complex with Lys 63
      linked di-ubiquitin.
AB  - NEMO is essential for activation of the NF-kappaB signaling pathway, which is
      regulated by ubiquitination of proteins. The C-terminal leucine zipper of NEMO
      and its adjacent coiled-coil region (CC2-LZ) reportedly bind to linear ubiquitin
      chains with 1 microM affinity and to Lys 63-linked chains with 100 microM
      affinity. Here we report the crystal structure of the CC2-LZ region of mouse NEMO
      in complex with Lys 63-linked di-ubiquitin (K63-Ub(2)) at 2.7A resolution. The
      ubiquitin-binding region consists of a 130A-long helix and forms a parallel
      coiled-coil dimer. The Ile 44-centered hydrophobic patch of ubiquitin is
      recognized in the middle of the NEMO ubiquitin-binding region. NEMO interacts
      with each K63-Ub(2)via a single ubiquitin-binding site, consistent with low
      affinity binding with K63-Ub(2).

PMID- 19766638
TI  - The prion or the related Shadoo protein is required for early mouse
      embryogenesis.
AB  - The prion protein PrP has a key role in transmissible spongiform encephalopathies
      but its biological function remains largely unknown. Recently, a related protein,
      Shadoo, was discovered. Its biological properties and brain distribution
      partially overlap that of PrP. We report that the Shadoo-encoding gene knockdown
      in PrP-knockout mouse embryos results in a lethal phenotype, occurring between E8
      and E11, not observed on the wild-type genetic background. It reveals that these
      two proteins play a shared, crucial role in mammalian embryogenesis, explaining
      the lack of severe phenotype in PrP-knockout mammals, an appreciable step towards
      deciphering the biological role of this protein family.

PMID- 19766639
TI  - Radioembolization for hepatocellular carcinoma using Yttrium-90 microspheres: a
      comprehensive report of long-term outcomes.
AB  - BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) has limited treatment options;
      long-term outcomes following intra-arterial radiation are unknown. We assessed
      clinical outcomes of patients treated with intra-arterial yttrium-90 microspheres
      (Y90). METHODS: Patients with HCC (n = 291) were treated with Y90 as part of a
      single-center, prospective, longitudinal cohort study. Toxicities were recorded
      using the Common Terminology Criteria version 3.0. Response rate and time to
      progression (TTP) were determined using World Health Organization (WHO) and
      European Association for the Study of the Liver (EASL) guidelines. Survival by
      stage was assessed. Univariate/multivariate analyses were performed. RESULTS: A
      total of 526 treatments were administered (mean, 1.8; range, 1-5). Toxicities
      included fatigue (57%), pain (23%), and nausea/vomiting (20%); 19% exhibited
      grade 3/4 bilirubin toxicity. The 30-day mortality rate was 3%. Response rates
      were 42% and 57% based on WHO and EASL criteria, respectively. The overall TTP
      was 7.9 months (95% confidence interval, 6-10.3). Survival times differed between
      patients with Child-Pugh A and B disease (A, 17.2 months; B, 7.7 months; P =
      .002). Patients with Child-Pugh B disease who had portal vein thrombosis (PVT)
      survived 5.6 months (95% confidence interval, 4.5-6.7). Baseline age; sex;
      performance status; presence of portal hypertension; tumor distribution; levels
      of bilirubin, albumin, and alpha-fetoprotein; and WHO/EASL response rate
      predicted survival. CONCLUSIONS: Patients with Child-Pugh A disease, with or
      without PVT, benefited most from treatment. Patients with Child-Pugh B disease
      who had PVT had poor outcomes. TTP and overall survival varied by patient stage
      at baseline. These data can be used to design future Y90 trials and to describe
      Y90 as a potential treatment option for patients with HCC.

PMID- 19766640
TI  - Delayed-release oral mesalamine 4.8 g/day (800-mg tablet) is effective for
      patients with moderately active ulcerative colitis.
AB  - BACKGROUND AND AIMS: It is not clear what induction dose of mesalamine is optimal
      for treating patients with mildly and moderately active ulcerative colitis (UC).
      This study was conducted to determine the efficacy and safety of mesalamine 4.8
      g/day compared with 2.4 g/day for the treatment of moderately active UC. METHODS:
      A multicenter, randomized, double-blind, 6-week, active-control study (ASCEND
      III) was conducted to assess the noninferiority of delayed-release mesalamine 4.8
      g/day (Asacol HD, 800-mg tablet; Procter & Gamble, Pharmaceuticals, Inc, Mason,
      Ohio) with 2.4 g/day (Asacol, 400-mg tablet; Procter & Gamble Pharmaceuticals,
      Inc) in 772 patients with moderately active UC. The primary endpoint was
      treatment success (overall improvement) at week 6, defined as improvement in the
      Physician's Global Assessment (based on clinical assessments of rectal bleeding,
      stool frequency, and sigmoidoscopy), with no worsening in any individual clinical
      assessment. RESULTS: The primary objective of noninferiority was met. Seventy
      percent (273 of 389) of patients who received 4.8 g/day of mesalamine achieved
      treatment success at week 6, compared with 66% (251 of 383) of patients receiving
      2.4 g/day (95% confidence interval for 2.4 g/day minus 4.8 g/day, -11.2 to 1.9).
      In addition, 43% of patients who received 4.8 g/day mesalamine achieved clinical
      remission at week 6 compared with 35% of patients who received 2.4 g/day (P =
      .04). A therapeutic advantage for the 4.8 g/day dose was observed among patients
      previously treated with corticosteroids, oral mesalamines, rectal therapies, or
      multiple UC medications. Both regimens were well-tolerated with similar adverse
      events. CONCLUSIONS: Delayed-release mesalamine 4.8 g/day (800-mg tablet) is
      efficacious and well-tolerated in patients with moderately active UC.

PMID- 19766641
TI  - Celiac disease: from pathogenesis to novel therapies.
AB  - Celiac disease has become one of the best-understood HLA-linked disorders.
      Although it shares many immunologic features with inflammatory bowel disease,
      celiac disease is uniquely characterized by (1) a defined trigger (gluten
      proteins from wheat and related cereals), (2) the necessary presence of HLA-DQ2
      or HLA-DQ8, and (3) the generation of circulating autoantibodies to the enzyme
      tissue transglutaminase (TG2). TG2 deamidates certain gluten peptides, increasing
      their affinity to HLA-DQ2 or HLA-DQ8. This generates a more vigorous CD4(+) T
      helper 1 T-cell activation, which can result in intestinal mucosal inflammation,
      malabsorption, and numerous secondary symptoms and autoimmune diseases. Moreover,
      gluten elicits innate immune responses that act in concert with the adaptive
      immunity. Exclusion of gluten from the diet reverses many disease manifestations
      but is usually not or less efficient in patients with refractory celiac disease
      or associated autoimmune diseases. Based on the advanced understanding of the
      pathogenesis of celiac disease, targeted nondietary therapies have been devised,
      and some of these are already in phase 1 or 2 clinical trials. Examples are
      modified flours that have been depleted of immunogenic gluten epitopes,
      degradation of immunodominant gliadin peptides that resist intestinal proteases
      by exogenous endopeptidases, decrease of intestinal permeability by blockage of
      the epithelial ZOT receptor, inhibition of intestinal TG2 activity by
      transglutaminase inhibitors, inhibition of gluten peptide presentation by HLA-DQ2
      antagonists, modulation or inhibition of proinflammatory cytokines, and induction
      of oral tolerance to gluten. These and other experimental therapies will be
      discussed critically.

PMID- 19766642
TI  - ERK1/2-dependent vascular endothelial growth factor signaling sustains cyst
      growth in polycystin-2 defective mice.
AB  - BACKGROUND & AIMS: Severe polycystic liver disease can complicate adult dominant
      polycystic kidney disease, a genetic disease caused by defects in polycystin-1
      (Pkd1) or polycystin-2 (Pkd2). Liver cyst epithelial cells (LCECs) express
      vascular endothelial growth factor (VEGF) and its receptor, VEGFR-2. We
      investigated the effects of VEGF on liver cyst growth and autocrine VEGF
      signaling in mice with Pkd1 and Pkd2 conditional knockouts. METHODS: We studied
      mice in which Pkd1 or Pkd2 were conditionally inactivated following exposure to
      tamoxifen; these mice were called Pkd1(flox/-):pCxCreER (Pkd1KO) and Pkd2(flox/
      ):pCxCreER (Pkd2KO). RESULTS: Pkd1KO and Pkd2KO mice developed liver defects;
      their LCECs expressed VEGF, VEGFR-2, hypoxia-inducible factor (HIF)-1alpha,
      phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2), and
      proliferating cell nuclear antigen (PCNA). In Pkd2KO but not Pkd1KO mice,
      exposure to the VEGFR-2 inhibitor SU5416 significantly reduced liver cyst
      development, liver/body weight ratio, and expression of pERK and PCNA. VEGF
      secretion and phosphorylation of ERK1/2 and VEGFR-2 were significantly increased
      in cultured LCECs from Pkd2KO compared with Pkd1KO mice. Inhibition of protein
      kinase A (PKA) reduced VEGF secretion and pERK1/2 expression. Addition of VEGF to
      LCECs from Pkd2KO mice increased phosphorylated VEGFR-2 and phosphorylated
      mitogen signal-regulated kinase (MEK) expression and induced phosphorylation of
      ERK1/2; this was inhibited by SU5416. Expression of HIF-1alpha increased in
      parallel with secretion of VEGF following LCEC stimulation. VEGF-induced cell
      proliferation was inhibited by the MEK inhibitor U1026 and by ERK1/2 small
      interfering RNA. CONCLUSIONS: The PKA-ERK1/2-VEGF signaling pathway promotes
      growth of liver cysts in mice. In Pkd2-defective LCECs, PKA-dependent ERK1/2
      signaling controls HIF-1alpha-dependent VEGF secretion and VEGFR-2 signaling.
      Autocrine and paracrine VEGF signaling promotes the growth of liver cysts in
      Pkd2KO mice. VEGF inhibitors might be used to treat patients with polycystic
      liver disease.

PMID- 19766644
TI  - Differential importance of glucose-dependent insulinotropic polypeptide vs
      glucagon-like peptide 1 receptor signaling for beta cell survival in mice.
AB  - BACKGROUND & AIMS: Glucagon-like peptide 1 (GLP-1) and glucose-dependent
      insulinotropic polypeptide (GIP) activate pathways involved in beta cell survival
      and proliferation in vitro; we compared the relative importance of exogenous and
      endogenous GIP receptor (GIPR) and GLP-1 receptor (GLP-1R) activation for beta
      cell cytoprotection in mice. METHODS: The effects of incretin hormone receptor
      signaling on beta cell regeneration and survival were assessed in mice following
      administration of streptozotocin in the absence or presence of the GIPR agonist
      [D-Ala(2)]-GIP (D-GIP), the GLP-1R agonist exendin-4, or the dipeptidyl peptidase
      4 inhibitor sitagliptin. Beta cell survival was assessed in Gipr(-/-) mice given
      streptozotocin and by gene expression profiling of RNA from islets isolated from
      Glp1r(-/-) and Gipr(-/-) mice. The antiapoptotic actions of sitagliptin were
      assessed in wild-type and dual incretin receptor knockout (DIRKO) mice. RESULTS:
      Administration of exendin-4 for 7 or 60 days improved blood glucose and insulin
      levels, reduced islet cell apoptosis, and increased pancreatic insulin content
      and beta cell mass. In contrast, D-GIP was less effective at improving these
      parameters under identical experimental conditions. Furthermore, Gipr(-/-) mice
      did not exhibit increased sensitivity to streptozotocin-induced diabetes.
      Sitagliptin reduced hemoglobin A(1c) levels and increased plasma and pancreatic
      levels of insulin after streptozotocin administration to wild-type mice.
      Sitagliptin reduced the levels of activated caspase-3 in wild-type islets but not
      in beta cells from DIRKO mice. CONCLUSIONS: There are functionally important
      differences in the pharmacologic and physiologic roles of incretin receptors in
      beta cells. GLP-1R signaling exerts more robust control of beta cell survival,
      relative to GIPR activation or dipeptidylpeptidase-4 inhibition in mice in vivo.

PMID- 19766643
TI  - Predicting clinical and histologic outcomes based on standard laboratory tests in
      advanced chronic hepatitis C.
AB  - BACKGROUND & AIMS: Predictors of clinical outcomes and histologic progression
      among patients with chronic hepatitis C and advanced fibrosis are poorly defined.
      We developed statistical models to predict clinical and histologic outcomes in
      such patients. METHODS: Baseline demographic, clinical, and histologic data from
      Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) Trial
      participants were subjected to multivariate analyses to determine their ability
      to predict clinical outcomes (ascites, spontaneous bacterial peritonitis, Child
      Turcotte-Pugh score >or=7 on 2 consecutive visits, variceal bleeding, hepatic
      encephalopathy, and liver-related death) and histologic outcome (>or=2-point
      increase in Ishak fibrosis stage) during the 3.5 years of the trial. RESULTS: Of
      1050 randomized patients, 135 had 1 or more clinical outcomes a median of 23
      (range, 1-45) months after randomization. Factors associated with a clinical
      outcome in multivariate analyses were higher aspartate aminotransferase/alanine
      aminotransferase ratio, lower albumin, lower platelet count, higher total
      bilirubin, and more advanced Ishak fibrosis score (P < .0001). The cumulative 3.5
      year incidence of a clinical outcome was 2% in the lowest and 65% in the highest
      risk group. Of 547 patients without cirrhosis at baseline and at least 1 follow
      up biopsy, 152 had a histologic outcome. Independent variables associated with a
      histologic outcome were higher body mass index, lower platelet count, and greater
      hepatic steatosis (P < .0001). CONCLUSIONS: In patients with chronic hepatitis C
      and advanced fibrosis, risk of clinical complications and fibrosis progression
      during 3.5 years can be predicted using baseline laboratory tests and histologic
      data. Our models may be useful in counseling patients and determining the
      frequency of monitoring.

PMID- 19766645
TI  - Randomized study of peginterferon-alpha2a plus ribavirin vs peginterferon-alpha2b
      plus ribavirin in chronic hepatitis C.
AB  - BACKGROUND & AIMS: Ribavirin (RBV) combined with either pegylated interferon
      (PegIFN) alpha2a or PegIFNalpha2b is the standard of care for chronic hepatitis C
      virus (HCV) infection. Due to the lack of head-to-head studies, the 2 PegIFNs
      have not been directly compared. The endpoints of our study were safety and
      antiviral efficacy of the 2 regimens. METHODS: Treatment-naive patients with
      chronic hepatitis C were randomly (1:1) assigned after stratification for HCV
      genotype to receive either 1.5 mcg/Kg/week PegIFNalpha2b plus RBV 800-1200 mg/day
      or 180 mcg/week PegIFNalpha2a plus RBV 800-1200 mg/day for 24 or 48 weeks
      according to HCV genotype. The study was powered to detect a difference of at
      least 10% in safety and efficacy of the 2 regimens. RESULTS: The 212 patients on
      PegIFNalpha2a and the 219 patients on PegIFNalpha2b had similar baseline
      characteristics, including cirrhosis (20% vs 18%, respectively). By intention to
      treat, the 2 groups showed similar rates of treatment-related serious adverse
      events (1% vs 1%, respectively) and drop out rates for adverse effects (7% vs 6%,
      respectively). Overall, sustained virologic response (SVR) rate was higher in
      PegIFNalpha2a than in PegIFNalpha2b patients (66% vs 54%, respectively, P = .02),
      being 48% vs 32% in the 222 HCV-1 and -4 patients (P = .04), and 96% vs 82%,
      respectively, in the 143 HCV-2 patients (P = .01). PegIFNalpha2a independently
      predicted SVR in the logistic regression analysis (odds ratio, 1.88; 95%
      confidence interval: 1.20-2.96). CONCLUSIONS: Although the 2 regimens showed a
      similar safety profile, the PegIFNalpha2a-based treatment yielded significantly
      more SVR than PegIFNalpha2b.

PMID- 19766646
TI  - Long-term probability of and mortality from de novo malignancy after liver
      transplantation.
AB  - BACKGROUND & AIMS: Information about malignancies that arise in patients after
      liver transplantation comes from volunteer registry databases and single-center
      retrospective studies. We analyzed a multicenter, prospectively obtained database
      to assess the probabilities of and risk factors for de novo malignancies in
      patients after liver transplantation. METHODS: We analyzed the National Institute
      of Diabetes and Digestive and Kidney Diseases' liver transplantation database of
      798 adults who received transplants from April 1990 to June 1994 and long-term
      follow-up data through January 2003. In this patient population, 171 adult
      patients developed 271 de novo malignancies. Of these malignancies, 147 were skin
      related, 29 were hematologic, and 95 were solid organ cancers; we focused on
      nonskin malignancies. RESULTS: The probability of developing any nonskin
      malignancy was highest in patients with primary sclerosing cholangitis (PSC; 22%
      at 10 years) or alcohol-related liver disease (ALD; 18% at 10 years); all other
      diagnoses had a 10% probability. Multivariate analysis indicated that increased
      age by decade (hazard ratio [HR] = 1.33, P = .01), a history of smoking (HR =
      1.6, P = .046), PSC (HR = 2.5, P = .001), and ALD (HR = 2.1, P = .01) were
      associated with development of solid malignancies after liver transplantation.
      The probabilities of death after diagnosis of hematologic and solid malignancy
      were 44.0% and 38.0% at 1 year and 57.6% and 53.1% at 5 years, respectively.
      CONCLUSIONS: De novo malignancy primarily affects patients with PSC or ALD,
      compared to other transplant recipients, with a significant impact on long-term
      survival.

PMID- 19766647
TI  - Temporal expression of hepatic estrogen receptor 1, vitellogenin1 and
      vitellogenin2 in European silver eels.
AB  - Because European silver eels have never been caught during or after their 6000-km
      reproductive migration to the Sargasso Sea, all existing knowledge on their
      sexual maturation comes from hormonal stimulation. Silver eels that start their
      oceanic migration are still immature with pre-vitellogenic oocytes. Hence we
      assumed that vitellogenesis should start with the expression of the estrogen
      receptor in the liver before the circulating 17beta-estradiol (E2) can have any
      effect. In this study we followed the hepatic vitellogenesis upon 4 weekly
      injections with carp pituitary extracts (CPE). New molecular primers for the
      expression of the estrogen receptor 1 (esr1), vitellogenin1 (vtg1) and
      vitellogenin2 (vtg2) in the liver were developed. Sequences of vtg2 and esr1 were
      not previously described in Anguilla anguilla. All eels showed weekly increase of
      the eye size and pectoral fin length, which are signs of early maturation. The
      same occurred with the gonadosomatic index, the oocyte stage and diameter, and
      number of deposited fat droplets. Early vitellogenesis appeared as a 3-step
      process (1) E2-levels and esr1 expression were significantly increased already
      after one injection, (2) vtg1 and vtg2 expression were significantly increased
      after one and two injections, respectively, and (3) vtg1 and vtg2 expression
      increased further after three and four injections. Then also plasma calcium
      (corresponds with plasma vitellogenin) increased and yolk globuli appeared in the
      oocytes. These results show that esr1 is the first of the three genes examined
      that is expressed during the onset of hepatic vitellogenesis. Furthermore,
      ovarian vitellogenesis (appearance of yolk globuli in oocytes) occurs 1-2 weeks
      later than the onset of hepatic vitellogenesis.

PMID- 19766648
TI  - Whole cell imaging reveals novel modular features of the exomembrane system of
      the malaria parasite, Plasmodium falciparum.
AB  - During its intra-erythrocytic development Plasmodium falciparum establishes a
      membrane network beyond its own limiting membrane in the cytoplasm of its host.
      These membrane structures play an important role in the trafficking of virulence
      proteins to the erythrocyte surface, however their ultrastructure is only partly
      defined and there is on-going debate regarding their origin, organisation and
      connectivity. We have used two whole cell imaging modalities to explore the
      topography of parasitised erythrocytes. Three-dimensional structured illumination
      microscopy provides resolution beyond the optical diffraction limit and permits
      analysis of fluorescently labelled whole cells. Immunoelectron tomography offers
      the possibility of high resolution imaging of individual ultrastructural features
      in a cellular context. Combined with serial sectioning and immunogold labelling,
      this technique permits precise mapping of whole cell architecture. We show that
      the P. falciparum exported secretory system comprises a series of modular units,
      comprising flattened cisternae, known as Maurer's clefts, tubular connecting
      elements, two different vesicle populations and electron-dense structures that
      have fused with the erythrocyte membrane. The membrane network is not continuous,
      pointing to an important role for vesicle-mediated transport in the delivery of
      cargo to different destinations in the host cell.

PMID- 19766649
TI  - Phylogeographical, ecological and biological patterns shown by nuclear (ssrRNA
      and gGAPDH) and mitochondrial (Cyt b) genes of trypanosomes of the subgenus
      Schizotrypanum parasitic in Brazilian bats.
AB  - The genetic diversity and phylogeographical patterns of Trypanosoma species that
      infect Brazilian bats were evaluated by examining 1043 bats from 63 species of
      seven families captured in Amazonia, the Pantanal, Cerrado and the Atlantic
      Forest biomes of Brazil. The prevalence of trypanosome-infected bats, as
      estimated by haemoculture, was 12.9%, resulting in 77 cultures of isolates, most
      morphologically identified as Trypanosoma cf. cruzi, classified by barcoding
      using partial sequences from ssrRNA gene into the subgenus Schizotrypanum and
      identified as T. cruzi (15), T. cruzi marinkellei (37) or T. cf. dionisii (25).
      Phylogenetic analyses using nuclear ssrRNA, glycosomal glyceraldehyde 3-phosphate
      dehydrogenase (gGAPDH) and mitochondrial cytochrome b (Cyt b) gene sequences
      generated three clades, which clustered together forming the subgenus
      Schizotrypanum. In addition to vector association, bat trypanosomes were related
      by the evolutionary history, ecology and phylogeography of the bats. Trypanosoma
      cf. dionisii trypanosomes (32.4%) infected 12 species from four bat families
      captured in all biomes, from North to South Brazil, and clustered with T.
      dionisii from Europe despite being separated by some genetic distance.
      Trypanosoma cruzi marinkellei (49.3%) was restricted to phyllostomid bats from
      Amazonia to the Pantanal (North to Central). Trypanosoma cruzi (18.2%) was found
      mainly in vespertilionid and phyllostomid bats from the Pantanal/Cerrado and the
      Atlantic Forest (Central to Southeast), with a few isolates from Amazonia.

PMID- 19766650
TI  - Methods for comprehensive identification of membrane proteins recognized by a
      large number of monoclonal antibodies.
AB  - In order to isolate monoclonal antibodies (mAbs) that bind to tumor-associated
      antigens (Ags) we developed the following strategy. Using the phage-display Ab
      library we isolated a large number of mAbs that bind to the surface of human
      tumor cells. The mAbs were individually screened by immunostaining, and clones
      that preferentially and strongly stained the malignant cells were chosen.
      Thereafter, the Ags recognized by the mAbs were identified. For identification of
      the Ags by MS candidate molecules had to be purified either by
      immunoprecipitation or by affinity chromatography. We isolated several hundred
      mAbs that showed cancer-specific staining patterns. In order to identify the Ags
      that were recognized by the numerous mAbs within a short time we developed two
      methods. Using the GFC [grouping of clones by flow cytometry (FCM)] method many
      Abs could be grouped by comparing the staining patterns of FCM. Members in each
      group turned out to bind to the same molecule in many cases. After a candidate Ag
      was revealed, the polypeptide corresponding to its extracellular portion was
      prepared and used for identification of clones that bound to the Ag among all the
      mAbs by SITE (simultaneous identification of clones through three dimensional
      ELISA) method. Both methods can be generally applicable to various kinds of
      membrane proteins and the mAbs against them.

PMID- 19766651
TI  - Temporal and spatial metabolic rate variation in the Antarctic springtail
      Gomphiocephalus hodgsoni.
AB  - Spatial and temporal environmental variation in terrestrial Antarctic ecosystems
      are known to impact species strongly at a local scale, but the ways in which
      organisms respond (e.g. physiologically, behaviourally) to such variation are
      poorly understood. Further, very few studies have attempted to assess inter
      annual variability of such responses. Building on previous work demonstrating
      intra-seasonal variation in standard metabolic rate in the springtail
      Gomphiocephalushodgsoni, we investigated variation in metabolic activity of G.
      hodgsoni across two austral summer periods at Cape Bird, Ross Island. We also
      examined the influence of spatial variation by comparing metabolic rates of G.
      hodgsoni at Cape Bird with those from two other isolated continental locations
      within Victoria Land (Garwood and Taylor Valleys). We found significant
      differences between metabolic rates across the 2 years of measurement at Cape
      Bird. In addition, standard metabolic rates of G. hodgsoni obtained from Garwood
      and Taylor Valleys were significantly higher than those at Cape Bird where
      habitats are comparable, but environmental characteristics differ (e.g.
      microclimatic temperatures are higher). We discuss potential underlying causes of
      these metabolic rate variation patterns, including those related to differences
      among individuals (e.g. physiological and genetic differences), locations (e.g.
      habitat quality and microclimatic regime differences) and populations (e.g.
      acclimation differences among G. hodgsoni populations in the form of metabolic
      cold adaptation (MCA)).

PMID- 19766652
TI  - Retinal-protein interactions in halorhodopsin from Natronomonas pharaonis:
      binding and retinal thermal isomerization catalysis.
AB  - Halorhodopsin from Natronomonas pharaonis (NpHR) is a member of the retinal
      protein group and serves as a light-driven chloride pump in which chloride ions
      are transported through the membrane following light absorption by the retinal
      chromophore. In this study, we examined two main issues: (1) factors controlling
      the binding of the retinal chromophore to the NpHR opsin and (2) the ability of
      the NpHR opsin to catalyze the thermal isomerization of retinal isomers. We have
      revealed that the reconstitution process of pharaonis HR (NpHR) pigment from its
      apoprotein and all-trans retinal depends on the pH, and the process has a pK(a)
      of 5.8+/-0.1. It was proposed that this pK(a) is associated with the pK(a) of the
      lysine residue that binds the retinal chromophore (Lys256). The pigment formation
      is regulated by the concentration of sodium chloride, and the maximum yield was
      observed at 3.7 M NaCl. The low yield of pigment in a lower concentration of NaCl
      (<3 M) may be due to an altered conformation adopted by the apomembrane, which is
      not capable of forming the pigment. Unexpectedly and unlike the apomembrane of
      bacteriorhodopsin, NpHR opsin produces pigments with 11-cis retinal and 9-cis
      retinal owing to the thermal isomerization of these retinal isomers to all-trans
      retinal. The isomerization rate depends on the pH, and it is faster at a higher
      pH. The pK(a) value of the isomerization process is similar to the pK(a) of the
      binding process of these retinals, which suggests that Lys256 is also involved in
      the isomerization process. The isomerization is independent of the sodium
      chloride concentration. However, in the absence of sodium chloride, the
      apoprotein adopts such a conformation, which does not prevent the isomerization
      of retinal, but it prevents a covalent bond formation with the lysine residue.
      The rate and the thermodynamic parameter analysis of the retinal isomerization by
      NpHR apoprotein led to the conclusion that the apomembrane catalyzes the
      isomerization via a triplet mechanism.

PMID- 19766653
TI  - alpha-Lactalbumin, engineered to be nonnative and inactive, kills tumor cells
      when in complex with oleic acid: a new biological function resulting from partial
      unfolding.
AB  - HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a tumoricidal
      complex consisting of partially unfolded protein and fatty acid and was first
      identified in casein fractions of human breast milk. The complex can be produced
      from its pure components through a modified chromatographic procedure where
      preapplied oleic acid binds with partially unfolded alpha-lactalbumin on the
      stationary phase in situ. Because native alpha-lactalbumin itself cannot trigger
      cell death, HAMLET's remarkable tumor-selective cytotoxicity has been strongly
      correlated with the conformational change of the protein upon forming the
      complex, but whether a recovery to the native state subsequently occurs upon
      entering the tumor cell is yet unclear. To this end, we utilize a recombinant
      variant of human alpha-lactalbumin in which all eight cysteine residues are
      substituted for alanines (rHLA(all-Ala)), rendering the protein nonnative and
      biologically inactive under all conditions. The HAMLET analogue formed from the
      complex of rHLA(all-Ala) and oleic acid (rHLA(all-Ala)-OA) exhibited equivalent
      strong tumoricidal activity against lymphoma and carcinoma cell lines and was
      shown to accumulate within the nuclei of tumor cells, thus reproducing the
      cellular trafficking pattern of HAMLET. In contrast, the fatty acid-free rHLA(all
      Ala) protein associated with the tumor cell surface but was not internalized and
      lacked any cytotoxic activity. Structurally, whereas HAMLET exhibited some
      residual native character in terms of NMR chemical shift dispersion, rHLA(all
      Ala)-OA showed significant differences to HAMLET and, in fact, was found to be
      devoid of any tertiary packing. The results identify alpha-lactalbumin as a
      protein with strikingly different functions in the native and partially unfolded
      states. We posit that partial unfolding offers another significant route of
      functional diversification for proteins within the cell.

PMID- 19766654
TI  - Identification of a function-specific mutation of clathrin heavy chain (CHC)
      required for p53 transactivation.
AB  - The p53 pathway is activated in response to various cellular stresses to protect
      cells from malignant transformation. We have previously shown that clathrin heavy
      chain (CHC), which is a cytosolic protein regulating endocytosis, is present in
      nuclei and binds to p53 to promote p53-mediated transcription. However, details
      of the binding interface between p53 and CHC remain unclear. Here, we report on
      the binding mode between p53 and CHC using mutation analyses and a structural
      model of the interaction generated by molecular dynamics. Structural modeling
      analyses predict that an Asn1288 residue in CHC is crucial for binding to p53. In
      fact, substitution of this Asn to Ala of CHC diminished its ability to interact
      with p53, leading to reduced activity to transactivate p53. Surprisingly, this
      mutation had little effect on receptor-mediated endocytosis. Thus, the function
      specific mutation of CHC will clarify physiological roles of CHC in the
      regulation of the p53 pathway.

PMID- 19766655
TI  - Identification of the interactions critical for propeptide-catalyzed folding of
      Tk-subtilisin.
AB  - Tk-subtilisin requires Ca(2+) for folding. This folding is accelerated by the
      chaperone function of its propeptide (Tkpro). Several Tkpro and Tk-subtilisin
      derivatives were constructed to examine whether the interactions between the C
      terminal extended region of Tkpro and Tk-subtilisin and Glu61/Asp63- and Glu201
      mediated hydrogen bonds at the domain interface are important for the chaperone
      function of Tkpro. The Tkpro derivatives with a series of C-terminal truncations
      and double mutations at Glu61 and Asp63 exhibited weaker chaperone functions than
      Tkpro for SA-subtilisin (active-site mutant of Tk-subtilisin). Good correlation
      was observed between their chaperone functions and binding abilities to the
      folded SA-subtilisin protein. These results suggest that the C-terminal extended
      region, Glu61, and Asp63 of Tkpro are not critical for folding of Tk-subtilisin
      but accelerate it by binding to a folding intermediate of Tk-subtilisin with a
      native-like structure at their binding sites. In contrast, Tkpro exhibited little
      chaperone function for E201A/SA-subtilisin. It could bind to the folded E201A/SA
      subtilisin protein with a lower association constant than that for SA-subtilisin.
      These results suggest a loop of Tkpro, which interacts with Glu201 of Tk
      subtilisin through hydrogen bonds and is required for folding of Tk-subtilisin by
      binding to a folding intermediate of Tk-subtilisin with a nonnative structure.
      Because this loop is fairly hydrophobic and tightly packs to the surface parallel
      helices of the central alphabetaalpha substructure of Tk-subtilisin, binding of
      this loop to Glu201 may induce association of these two helices and thereby
      formation of the alphabetaalpha substructure. We propose that Glu201-mediated
      interactions are critical for initiation of Tkpro-catalyzed folding of Tk
      subtilisin.

PMID- 19766656
TI  - The human alpha-lactalbumin molten globule: comparison of structural preferences
      at pH 2 and pH 7.
AB  - Structural investigations of molten globules provide an important contribution
      towards understanding protein folding pathways. A close similarity between
      equilibrium molten globule states and kinetic species observed during refolding
      has been reported for several proteins. However, the experimental conditions, and
      in particular the pH, under which the equilibrium and kinetic species are studied
      often differ significantly. For human alpha-lactalbumin (alpha-LA), the
      equilibrium molten globule is most often studied at pH 2, the so-called A-state,
      while kinetic refolding experiments are performed at neutral pH. alpha-LA
      contains a large number of acidic amino acid residues that may influence the
      properties of the molten globule differently at low and neutral pH. In this
      study, we investigate the structural preferences of the alpha-LA molten globule
      at pH 7 at the level of individual residues using nuclear magnetic resonance
      spectroscopy and compare these data with previous results obtained at pH 2. We
      show that differences exist in the conformational ensemble that describes the
      alpha-LA molten globule at these two pH values. The molten globule at pH 7 is
      generally less stable than that at the low pH A-state. Most notable are
      differences in the stability of structure for the C-helix and the calcium-binding
      loop that precedes it and differences in the contribution of long-range
      hydrophobic contacts between the N-terminal and C-terminal regions of the alpha
      domain to the stability of the molten globule. Our results are discussed in the
      context of previous studies of the alpha-LA molten globule and can be used to
      reconcile apparent discrepancies in published data relating to the C-helix. In
      the light of our results, the low pH A-state may not be the best model for the
      kinetic molten globule observed during refolding of alpha-LA. The pH-dependent
      effects reported here for alpha-LA may be of relevance in comparisons of
      equilibrium and kinetic molten globules of other proteins.

PMID- 19766657
TI  - Changing the DNA recognition specificity of the EcoDam DNA-(adenine-N6)
      methyltransferase by directed evolution.
AB  - EcoDam is an adenine-N6 DNA methyltransferase that methylates the GATC sites in
      the Escherichia coli genome. We have changed the target specificity of EcoDam
      from GATC to GATT by directed evolution, combining different random mutagenesis
      methods with restriction protection at GATT sites for selection and screening. By
      co-evolution of an enzyme library and a substrate library, we identified GATT as
      the best non-GATC site and discover a double mutation, R124S/P134S, as the first
      step to increase enzyme activity at GATT sites. After four generations of
      mutagenesis and selection, we obtained enzyme variants with new specificity for
      GATT. While the wild-type EcoDam shows no detectable activity at GATT sites in E.
      coli cells, some variants prefer methylation at GATT over GATC sites by about 10
      fold in cells. In vitro DNA methylation kinetics carried out under single
      turnover conditions using a hemimethylated GATC and a GATT oligonucleotide
      substrate confirmed that the evolved proteins prefer methylation of GATT sites to
      a similar degree. They show up to 1600-fold change in specificity in vitro and
      methylate the new GATT target site with 20% of the rate of GATC methylation by
      the wild-type enzyme, indicating good activity. We conclude that the new
      methyltransferases are fully functional in vivo and in vitro but show a new
      target-site specificity.

PMID- 19766658
TI  - The Red Tooth Hypothesis: A computational model of predator-prey relations,
      protean escape behavior and sexual reproduction.
AB  - This paper presents an extension of the Red Queen Hypothesis (hereafter, RQH)
      that we call the Red Tooth Hypothesis (RTH). This hypothesis suggests that
      predator-prey relations may play a role in the maintenance of sexual reproduction
      in many higher animals. RTH is based on an interaction between learning on the
      part of predators and evolution on the part of prey. We present a simple predator
      prey computer simulation that illustrates the effects of this interaction. This
      simulation suggests that the optimal escape strategy from the prey's standpoint
      would be to have a small number of highly reflexive, largely innate (and,
      therefore, very fast) escape patterns, but that would also be unlearnable by the
      predator. One way to achieve this would be for each individual in the prey
      population to have a small set of hard-wired escape patterns, but which were
      different for each individual. We argue that polymorphic escape patterns at the
      population level could be produced via sexual reproduction at little or no
      evolutionary cost and would be as, or potentially more, efficient than individual
      level protean (i.e., random) escape behavior. We further argue that, especially
      under high predation pressure, sexual recombination would be a more rapid, and
      therefore more effective, means of producing highly variable escape behaviors at
      the population level than asexual reproduction.

PMID- 19766659
TI  - Coexistence conditions for strains of influenza with immune cross-reaction.
AB  - The accumulation of cross-immunity in the host population is an important factor
      driving the antigenic evolution of viruses such as influenza A. Mathematical
      models have shown that the strength of temporary non-specific cross-immunity and
      the basic reproductive number are both key determinants for evolutionary
      branching of the antigenic phenotype. Here we develop deterministic and
      stochastic versions of one such model. We examine how the time of emergence or
      introduction of a novel strain affects co-existence with existing strains and
      hence the initial establishment of a new evolutionary branch. We also clarify the
      roles of cross-immunity and the basic reproductive number in this process. We
      show that the basic reproductive number is important because it affects the
      frequency of infection, which influences the long term immune profile of the host
      population. The time at which a new strain appears relative to the epidemic peak
      of an existing strain is important because it determines the environment the
      emergent mutant experiences in terms of the short term immune profile of the host
      population. Strains are more likely to coexist, and hence to establish a new
      clade in the viral phylogeny, when there is a significant time overlap between
      their epidemics. It follows that the majority of antigenic drift in influenza is
      expected to occur in the earlier part of each transmission season and this is
      likely to be a key surveillance period for detecting emerging antigenic novelty.

PMID- 19766660
TI  - Light-dependent orientation responses in animals can be explained by a model of
      compass cue integration.
AB  - The magnetic compass sense of animals is currently thought to be based on light
      dependent processes like the proposed radical pair mechanism. In accordance, many
      animals show orientation responses that depend on light. However, the orientation
      responses depend on the wavelength and irradiance of monochromatic light in
      rather complex ways that cannot be explained directly by the radical pair
      mechanism. Here, a radically different model is presented that can explain a vast
      majority of the complex observed light-dependent responses. The model put forward
      an integration process consisting of simple lateral inhibition between a normal
      functioning, light-independent magnetic compass (e.g. magnetite based) and a
      vision based skylight color gradient compass that misperceives compass cues in
      monochromatic light. Integration of the misperceived color compass cue and the
      normal magnetic compass not only explains most of the categorically different
      light-dependent orientation responses, but also shows a surprisingly good fit to
      how well the animals are oriented (r-values) under light of different wavelength
      and irradiance. The model parsimoniously suggests the existence of a single
      magnetic sense in birds (probably based on magnetic crystals).

PMID- 19766661
TI  - Computationally exact methods for stochastic periodic dynamics: Spatiotemporal
      dispersal and temporally forced transmission.
AB  - The dynamics of many diseases and populations possess distinct recurring phases.
      For example, many species breed only during a subset of the year and the
      infection dynamics of many pathogens have transmission rates that vary with
      season. Here I investigate computational methods for studying transient and long
      term behaviour of stochastic models which have periodic phases-several different
      potential techniques for studying long-term behaviour will be contrasted. I
      illustrate the results with two studies: The first is of a spatially realistic
      metapopulation model of malleefowl (Leipoa ocellata), a species which disperses
      only during a quarter of the year; this model is used to highlight the advantages
      and disadvantages of the particular methods presented. The second study is of a
      model for disease dynamics which incorporates seasonality in both the rate of
      within-population transmission and also in the rate of transmission effected via
      aerosol importation. This model has applications to studying disease invasion and
      persistence in captive-breeding populations. We demonstrate, via comparison to
      appropriately matched models with constant transmission rates and also no aerosol
      transmission, that seasonality and aerosol importation may alter control choices,
      with possibly an increase in the threshold population size for local control
      surveillance, transfer of importance to limiting aerosol transmission, and the
      use of temporally targetted surveillance. The methodology presented is the gold
      standard for dealing with many phased processes in ecology and epidemiology, but
      its application is limited to systems of small size.

PMID- 19766662
TI  - "Pre-semantic" cognition revisited: critical differences between semantic aphasia
      and semantic dementia.
AB  - Patients with semantic dementia show a specific pattern of impairment on both
      verbal and non-verbal "pre-semantic" tasks, e.g., reading aloud, past tense
      generation, spelling to dictation, lexical decision, object decision, colour
      decision and delayed picture copying. All seven tasks are characterised by poorer
      performance for items that are atypical of the domain and "regularization errors"
      (irregular/atypical items are produced as if they were domain-typical). The
      emergence of this pattern across diverse tasks in the same patients indicates
      that semantic memory plays a key role in all of these types of "pre-semantic"
      processing. However, this claim remains controversial because semantically
      impaired patients sometimes fail to show an influence of regularity. This study
      demonstrates that (a) the location of brain damage and (b) the underlying nature
      of the semantic deficit affect the likelihood of observing the expected
      relationship between poor comprehension and regularity effects. We compared the
      effect of multimodal semantic impairment in the context of semantic dementia and
      stroke aphasia on the seven "pre-semantic" tasks listed above. In all of these
      tasks, the semantic aphasia patients were less sensitive to typicality than the
      semantic dementia patients, even though the two groups obtained comparable scores
      on semantic tests. The semantic aphasia group also made fewer regularization
      errors and many more unrelated and perseverative responses. We propose that these
      group differences reflect the different locus for the semantic impairment in the
      two conditions: patients with semantic dementia have degraded semantic
      representations, whereas semantic aphasia patients show deregulated semantic
      cognition with concomitant executive deficits. These findings suggest a
      reinterpretation of single-case studies of comprehension-impaired aphasic
      patients who fail to show the expected effect of regularity on "pre-semantic"
      tasks. Consequently, such cases do not demonstrate the independence of these
      tasks from semantic memory.

PMID- 19766663
TI  - Progranulin-associated primary progressive aphasia: a distinct phenotype?
AB  - The neuropsychological features of the primary progressive aphasia (PPA)
      syndromes continue to be defined. Here we describe a detailed neuropsychological
      case study of a patient with a mutation in the progranulin (GRN) gene who
      presented with progressive word-finding difficulty. Key neuropsychological
      features in this case included gravely impoverished propositional speech with
      anomia and prolonged word-finding pauses, impaired speech repetition most marked
      for sentences, and severely impaired verbal (with preserved spatial) short-term
      memory. There was a dissociated profile of performance on semantic processing
      tasks: visual semantic processing was intact, while within the verbal domain,
      verb comprehension was impaired and processing of nouns was intact on tasks
      requiring direct semantic processing but impaired on tasks requiring associative
      or inferential processing. Brain MRI showed asymmetric left cerebral atrophy
      particularly affecting the temporo-parietal junction, supero-lateral temporal and
      inferior frontal lobes. This case most closely resembles the PPA syndrome known
      as the logopenic/phonological aphasia variant (LPA) however there were also
      deficits of grammar and speech repetition suggesting an overlap with the
      progressive non-fluent aphasia (agrammatic) variant (PNFA). Certain prominent
      features of this case (in particular, the profile of semantic impairment) have
      not been emphasised in previous descriptions of LPA or PNFA, suggesting that GRN
      may cause an overlapping PPA syndrome but with a distinctive cognitive profile.
      This neuropsychological evidence suggests that GRN-PPA may result from damage
      involving the temporo-parietal junction and its functional connections in both
      the dorsal and ventral language networks, with implications for our understanding
      of language network pathophysiology.

PMID- 19766664
TI  - Inappropriate usage of the Brunner-Munzel test in recent voxel-based lesion
      symptom mapping studies.
AB  - Voxel-based lesion-symptom mapping (VLSM) techniques have been important in
      elucidating structure-function relationships in the human brain. Rorden, Karnath,
      and Bonilha (2007) introduced the non-parametric Brunner-Munzel rank order test
      as an alternative to parametric tests often used in VLSM analyses. However, the
      Brunner-Munzel statistic produces inflated z scores when used at any voxel where
      there are less than 10 subjects in either the lesion or no lesion groups.
      Unfortunately, a number of recently published VLSM studies using this statistic
      include relatively small patient populations, such that most (if not all)
      examined voxels do not meet the necessary criteria. We demonstrate the effects of
      inappropriate usage of the Brunner-Munzel test using a dataset included with
      MRIcron, and find large Type I errors. To correct for this we suggest that
      researchers use a permutation derived correction as implemented in current
      versions of MRIcron when using the Brunner-Munzel test.

PMID- 19766665
TI  - Chimpanzees' context-dependent tool use provides evidence for separable
      representations of hand and tool even during active use within peripersonal
      space.
AB  - Considerable attention has been devoted to behaviors in which tools are used to
      perform actions in extrapersonal space by extending the reach. Evidence suggests
      that these behaviors result in an expansion of the body schema and peripersonal
      space. However, humans often use tools to perform tasks within peripersonal space
      that cannot be accomplished with the hands. In some of these instances (e.g.,
      cooking), a tool is used as a substitute for the hand in order to pursue actions
      that would otherwise be hazardous. These behaviors suggest that even during the
      active use of tools, we maintain non-isomorphic representations that distinguish
      between our hands and handheld tools. Understanding whether such representations
      are a human specialization is of potentially great relevance to understand the
      evolutionary history of technological behaviors including the controlled use of
      fire. We tested six captive adult chimpanzees to determine whether they would
      elect to use a tool, rather than their hands, when acting in potentially
      hazardous vs. nonhazardous circumstances located within reach. Their behavior
      suggests that, like humans, chimpanzees represent the distinction between the
      hand vs. tool even during active use. We discuss the implications of this
      evidence for our understanding of tool use and its evolution.

PMID- 19766666
TI  - Personal experience and arithmetic meaning in semantic dementia.
AB  - Arithmetic skills are generally claimed to be preserved in semantic dementia
      (SD), suggesting functional independence of arithmetic knowledge from other
      aspects of semantic memory. However, in a recent case series analysis we showed
      that arithmetic performance in SD is not entirely normal. The finding of a direct
      association between severity of patients' semantic disorder and arithmetic
      impairment pointed to a closer relationship between semantic memory and
      arithmetic knowledge than previously acknowledged. The present study aimed to
      determine whether arithmetic performance in SD is subject to the same influences
      as has been found in other semantic domains, namely an autobiographical effect.
      SD patients were assessed on their ability to perform arithmetic in personally
      relevant compared to non-personal contexts. Patients who were regular, current
      followers of the television game show Countdown performed better on a simplified
      version of the show's number game compared to a conventional written calculation
      task, whereas patients with no experience of Countdown demonstrated the opposite
      pattern. SD patients showed better knowledge of multiplication table 'facts' when
      these were embedded in a situation relevant to their daily lives compared to a
      non-personal arithmetic task. They also performed better on a written calculation
      task when problems were presented as a monetary transaction compared to a
      standard arithmetic problem. A reference group of patients with Alzheimer's
      disease (AD) showed the reverse pattern. The findings provide convincing evidence
      that autobiographical relevance influences SD patients' arithmetic performance.
      Moreover, they challenge current views on conceptual number knowledge as a
      unitary, abstract competence.

PMID- 19766667
TI  - New quantification method for estradiol in the prostatic tissues of benign
      prostatic hyperplasia using liquid chromatography-tandem mass spectrometry.
AB  - Estrogen is suspected to play a role in the pathogenesis of benign prostatic
      hyperplasia (BPH) and prostate cancer. To clarify the role of estradiol (E2) in
      the prostatic tissues (prostatic tissue E2) during the development of prostatic
      disorders, we developed a new sensitive and specific quantification method for
      prostatic tissue E2 using liquid chromatography-tandem mass spectrometry (LC
      MS/MS). For the solid-phase extraction, E2 was purified by anion-exchange through
      an Oasis MAX cartridge. In addition, after the formation of 3-pentaflurobenzyl
      17beta-pyridinium-estradiol derivative (E2-PFBPY), E2-PFBPY was purified by
      cation-exchange through an Oasis WCX cartridge. These processes in the LC-MS/MS
      method improved the specificity and sensitivity for prostatic tissue E2
      measurement, compared to the radioimmunoassay (RIA) method. The validation tests
      showed that intra-day and inter-day precisions were both within +/-15% (except
      for 15.5% of the inter-day precision of the lowest concentration), with the
      accuracy ranging from 88 to 110%. The quantification limit of this assay was
      0.15pg/tube in our method, which was 80-fold more sensitive than that of the RIA
      method. With the use of our present method, the median E2 levels in the prostatic
      tissues in patients with BPH (n=20, median age: 71 years) were 12.0pg/g tissue
      (95% confidence interval=9.1-22.6pg/g tissue). Furthermore, the E2 levels
      increased significantly with aging. These results showed that our present method
      would be useful for elucidating the role of prostatic tissue E2 in the
      development of prostatic disorders with a small amount of tissue samples.

PMID- 19766668
TI  - Use of immobilised biocatalysts in the processing of cheese whey.
AB  - Food processing industry operations need to comply with increasingly more
      stringent environmental regulations related to the disposal or utilisation of by
      products and wastes. These include growing restrictions on land spraying with
      agro-industrial wastes, and on disposal within landfill operations, and the
      requirements to produce end products that are stabilised and hygienic. Much of
      the material generated as wastes by the dairy processing industries contains
      components that could be utilised as substrates and nutrients in a variety of
      microbial/enzymatic processes, to give rise to added-value products. A good
      example of a waste that has received considerable attention as a source of added
      value products is cheese whey. The carbohydrate reservoir of lactose (4-5%) in
      whey and the presence of other essential nutrients make it a good natural medium
      for the growth of microorganisms and a potential substrate for bioprocessing
      through microbial fermentation. Immobilised cell and enzyme technology has also
      been applied to whey bioconversion processes to improve the economics of such
      processes. This review focuses upon the elaboration of a range of immobilisation
      techniques that have been applied to produce valuable whey-based products. A
      comprehensive literature survey is also provided to illustrate numerous
      immobilisation procedures with particular emphasis upon lactose hydrolysis, and
      ethanol and lactic acid production using immobilised biocatalysts.

PMID- 19766669
TI  - CD62L defines a subset of pathogen-specific bovine CD4 with central memory cell
      characteristics.
AB  - Central memory T cells (Tcm) have not previously been characterized in cattle and
      any other ruminant species. Here we described two phenotypically and functionally
      different subsets of pathogen-specific memory CD4(+) T cells in cattle that
      survived infection with Mycoplasma mycoides subsp. mycoides small colony (MmmSC).
      The first subset is CD45RO(+)CD45R(-)CD62L(-) and comprises two thirds of IFN
      gamma producing CD4(+) T cells after MmmSC recall stimulation. The second is
      CD45RO(+)CD45R(-)CD62L(+) and represents the majority of proliferating CD4(+) T
      cells after 7 days of stimulation. Cell sorting experiments confirmed that both
      CD4(+)CD62L(+) and CD4(+)CD62L(-) subsets are present in vivo and proliferate
      independently in recall responses to MmmSC. In addition, MmmSC stimulation
      strongly decreased CCR7 and increased CCR5 transcripts levels in CD4(+)CD62L(-)
      cells whereas CD4(+)CD62L(+) were only slightly affected. High levels of recall
      proliferation but low IFN-gamma production, together with the capacity to
      preferentially migrate through the lymph nodes (i.e., expression of CD62L and
      CCR7), are characteristics of Tcm, in humans and mice. Tcm are associated with
      long-term protective immunity and a privileged target for vaccine development.
      Our results demonstrate the existence of Tcm in cattle and suggest that CD62L may
      serve as a marker to monitor Tcm in infections and vaccine development studies in
      ruminant.

PMID- 19766670
TI  - Construction of recombinant adenovirus vector containing a modified gene that
      codes for human hypoxia-inducible factor-1alpha without oxygen-dependent
      degradation domain.
AB  - The expression of hypoxia-inducible factor-1alpha (HIF-1alpha) in heart
      allografts is an important mechanism in response to ischemia/reperfusion (I/R)
      injury which represents the single major non-immunologic factor implicated in
      pathogenesis of chronic graft dysfunction (CGD). Adenoviral mediated
      overexpression of HIF-1alpha is a useful way to investigate the molecular
      mechanisms of I/R injury and the cardiac function during heart transplantation.
      The oxygen-dependent degradation (ODD) domain of HIF-1alpha can lead to
      degradation of the HIF-1alpha protein in normoxia. This will be an obstacle to
      steady expression of HIF-1alpha in heart allograft after transduction. In this
      study, we obtained the coding sequence of HIF-1alpha without ODD domain (HIF
      1alphaDeltaODD) through a PCR-based method, and then generated the HIF
      1alphaDeltaODD-expressing adenovirus. In normoxia, adenoviral mediated expression
      of HIF-1alphaDeltaODD shows constitutive activity in human cardiomyocytes, and
      can up-regulate heme oxygenase (HO)-1 mRNA levels significantly compared with the
      group transduced with HIF-1alpha-expressing adenovirus. The constructed HIF
      1alphaDeltaODD-expressing adenovirus can be used to transduce allografts in
      animal studies to investigate the mechanism of CGD and provide a useful model to
      study the regulation mechanisms of genes regulated by HIF-1alpha alone.

PMID- 19766671
TI  - Evidence for a separate mechanism of toxicity for the Type I and the Type II
      pyrethroid insecticides.
AB  - Neurotoxicity and mechanistic data were collected for six alpha-cyano pyrethroids
      (beta-cyfluthrin, cypermethrin, deltamethrin, esfenvalerate, fenpropathrin and
      lambda-cyhalothrin) and up to six non-cyano containing pyrethroids (bifenthrin, S
      bioallethrin [or allethrin], permethrin, pyrethrins, resmethrin [or its cis
      isomer, cismethrin] and tefluthrin under standard conditions. Factor analysis and
      multivariate dissimilarity analysis were employed to evaluate four independent
      data sets comprised of (1) fifty-six behavioral and physiological parameters from
      an acute neurotoxicity functional observatory battery (FOB), (2) eight
      electrophysiological parameters from voltage clamp experiments conducted on the
      Na(v)1.8 sodium channel expressed in Xenopus oocytes, (3) indices of efficacy,
      potency and binding calculated for calcium ion influx across neuronal membranes,
      membrane depolarization and glutamate released from rat brain synaptosomes and
      (4) changes in chloride channel open state probability using a patch voltage
      clamp technique for membranes isolated from mouse neuroblastoma cells. The
      pyrethroids segregated into Type I (T--syndrome-tremors) and Type II (CS syndrome
      -choreoathetosis with salivation) groups based on FOB data. Of the alpha-cyano
      pyrethroids, deltamethrin, lambda-cyhalothrin, cyfluthrin and cypermethrin
      arrayed themselves strongly in a dose-dependent manner along two factors that
      characterize the CS syndrome. Esfenvalerate and fenpropathrin displayed weaker
      response profiles compared to the non-cyano pyrethroids. Visual clustering on
      multidimensional scaling (MDS) maps based upon sodium ion channel and calcium
      influx and glutamate release dissimilarities gave similar groupings. The non
      cyano containing pyrethroids were arrayed in a dose-dependent manner along two
      different factors that characterize the T-syndrome. Bifenthrin was an outlier
      when MDS maps of the non-cyano pyrethroids were based on sodium ion channel
      characteristics and permethrin was an outlier when the MDS maps were based on
      calcium influx/glutamate release potency. Four of six alpha-cyano pyrethroids
      (lambda-cyfluthrin, cypermethrin, deltamethrin and fenpropathrin) reduced open
      chloride channel probability. The R-isomers of lambda-l-cyhalothrin reduced open
      channel probability whereas the S-isomers, antagonized the action of the R
      isomers. None of the non-cyano pyrethroids reduced open channel probability,
      except bioallethrin, which gave a weak response. Overall, based upon
      neurotoxicity data and the effect of pyrethroids on sodium, calcium and chloride
      ion channels, it is proposed that bioallethrin, cismethrin, tefluthrin,
      bifenthrin and permethrin belong to one common mechanism group and deltamethrin,
      lambda-cyhalothrin, cyfluthrin and cypermethrin belong to a second. Fenpropathrin
      and esfenvalerate occupy an intermediate position between these two groups.

PMID- 19766672
TI  - Syphilitic panuveitis with retinal necrosis in an HIV positive man confirmed by
      Treponema pallidum PCR.

PMID- 19766673
TI  - Biological rhythms, higher brain function, and behavior: Gaps, opportunities, and
      challenges.
AB  - Increasing evidence suggests that disrupted temporal organization impairs
      behavior, cognition, and affect; further, disruption of circadian clock genes
      impairs sleep-wake cycle and social rhythms which may be implicated in mental
      disorders. Despite this strong evidence, a gap in understanding the neural
      mechanisms of this interaction obscures whether biological rhythms disturbances
      are the underlying causes or merely symptoms of mental disorder. Here, we review
      current understanding, emerging concepts, gaps, and opportunities pertinent to
      (1) the neurobiology of the interactions between circadian oscillators and the
      neural circuits subserving higher brain function and behaviors of relevance to
      mental health, (2) the most promising approaches to determine how biological
      rhythms regulate brain function and behavior under normal and pathological
      conditions, (3) the gaps and challenges to advancing knowledge on the link
      between disrupted circadian rhythms/sleep and psychiatric disorders, and (4) the
      novel strategies for translation of basic science discoveries in circadian
      biology to clinical settings to define risk, prevent or delay onset of mental
      illnesses, design diagnostic tools, and propose new therapeutic strategies. The
      review is organized around five themes pertinent to (1) the impact of molecular
      clocks on physiology and behavior, (2) the interactions between circadian signals
      and cognitive functions, (3) the interface of circadian rhythms with sleep, (4) a
      clinical perspective on the relationship between circadian rhythm abnormalities
      and affective disorders, and (5) the pre-clinical models of circadian rhythm
      abnormalities and mood disorders.

PMID- 19766674
TI  - Dynamics of CD11c(+) dendritic cell subsets in lymph nodes draining the site of
      intestinal nematode infection.
AB  - Helminth parasites drive dominant Th2 responses through an as yet unidentified
      pathway. We have previously shown that the rodent gastrointestinal nematode
      Nippostrongylus brasiliensis secretes products which selectively activate in
      vitro-derived dendritic cells to induce Th2 responses on in vivo transfer. We now
      show that, during active infection with this parasite, the draining mesenteric
      lymph node dendritic cell population is altered significantly. Although there is
      substantial expansion of DC numbers during infection, the CD86(hi)-CD8alpha(int)
      CD11b(-) subset is markedly diminished, and expression levels of CD40, CD86 and
      CD103 are reduced. Notably, the reduced frequency of CD8alpha(int) DCs is evident
      only in those mesenteric lymph nodes draining the anterior site of infestation.
      In infections with the longer lived Heligmosomoides polygyrus, the proportion of
      CD8alpha(int) DCs in the MLNC falls to below 10% of total DC numbers by 35 days
      post-infection. Further, infection alters TLR responsiveness, as IL-12 production
      (as measured by ex vivo intracellular staining of CD11c(+) DCs) in response to
      LPS stimulation is reduced, while IL-6, TNF-alpha and in particular, IL-10 all
      increase following infection with either nematode parasite. These changes suggest
      the possibility that helminth parasites modulate gastrointestinal immunity both
      by inhibiting migration of CD8alpha(int) DCs to the draining lymph nodes, and
      modifying DC responsiveness in a manner which favours a Th2 outcome.

PMID- 19766675
TI  - Behavioral phenotyping of heterozygous acetylcholinesterase knockout (AChE+/-)
      mice showed no memory enhancement but hyposensitivity to amnesic drugs.
AB  - Decrease in the expression or activity of acetylcholinesterase (AChE) enzymatic
      activity results in increased cholinergic tonus in the brain and periphery, with
      concomitant regulations of nicotinic and muscarinic receptors expression. We
      generated AChE knockout mice and characterized the behavioral phenotype of
      heterozygous animals, focusing on learning and memory functions. Male and female,
      AChE+/- and AChE+/+ littermate controls (129 sv strain) were tested at 5-9 weeks
      of age. AChE activity was significantly decreased in the hippocampus and cortex
      of AChE+/- mice, but butyrylcholinesterase activity was preserved. AChE+/- mice
      failed to show any difference in terms of locomotion, exploration and anxiety
      parameters in the open-field test. Animals were then tested for place learning in
      the water-maze. They were trained using a 'sustained acquisition' protocol (3
      swim trials per day) or a 'mild acquisition' protocol (2 swim trials per day) to
      locate an invisible platform in fixed position (reference memory procedure).
      Then, during 3 days, they were trained to locate the platform in a variable
      position (working memory procedure). Learning profiles and probe test
      performances were similar for AChE+/- and AChE+/+ mice. Mice were then treated
      with the muscarinic receptor antagonist scopolamine (0.5, 5 mg/kg) 20 min before
      each training session. Scopolamine impaired learning at both doses in AChE+/+
      mice, but only at the highest dose in AChE+/- mice. Moreover, the
      intracerebroventricular injection of amyloid-beta25-35 peptide, 9 nmol, 7 days
      before water-maze acquisition, failed to induce learning deficits in AChE+/-
      mice, but impaired learning in AChE+/+ controls. The peptide failed to be toxic
      in forebrain structures of AChE+/- mice, since an increase in lipid peroxidation
      levels was measured in the hippocampus of AChE+/+ but not AChE+/- mice. We
      conclude that the increase in cholinergic tonus observed in AChE+/- mice did not
      result in increased memory functions but allowed a significant prevention of the
      deleterious effects of muscarinic blockade or amyloid toxicity.

PMID- 19766676
TI  - Long-term consequences of a single treatment of mice with an ultra-low dose of
      Delta9-tetrahydrocannabinol (THC).
AB  - A single administration of an extremely low dose (0.002 mg/kg) of Delta9
      tetrahydrocannabinol (THC; the psychoactive ingredient of marijuana) to ICR mice
      induced long-term cognitive deficits that lasted for at least 5 months. The
      behavioral deficits were detected by several tests that evaluated different
      aspects of memory and learning, including spatial navigation and spatial and non
      spatial recognition. Our findings point to possible deficits in attention or
      motivation that represent a common upstream cognitive process that may affect the
      performance of the mice in the different behavioral assays. Similar ultra-low
      doses of THC (3-4 orders of magnitude lower than doses that are known to evoke
      the acute effects of THC) also induced sustained activation of extracellular
      regulated kinase (ERK1/2) in the cerebellum, indicating that a single injection
      of such low doses of the cannabinoid drug can stimulate neuronal regulatory
      mechanisms. The relevance of these findings to the behavioral consequences of
      chronic exposure to marijuana is discussed.

PMID- 19766677
TI  - Effects of chlordiazepoxide on predator odor-induced reductions of playfulness in
      juvenile rats.
AB  - The extent to which a non-sedative dose of chlordiazepoxide (CDP) is able to
      modify the behavioral responses toward a predator odor was assessed in juvenile
      rats. Play behavior was suppressed and defensive behaviors were enhanced in the
      presence of a collar previously worn by a cat, when tested 24 h later in the same
      context as that where the exposure occurred, and when tested in a context
      different than that in which the exposure occurred for up to 3 h after exposure.
      CDP had no effect on the ability of cat odor to suppress play when rats were
      tested in the presence of the odor or when tested 24 h later in the same context
      where that exposure occurred. When rats were exposed to a worn cat collar in
      their home cage and tested in a different context CDP attenuated the ability of
      cat odor to reduce one measure of play (nape contacts) but not another measure
      (pins). Rats had an opportunity to hide during testing and CDP either decreased
      hiding or increased risk assessment from within the hide box in all of the
      testing scenarios. These data suggest that CDP can alter the defensive strategy
      used by juvenile rats that are confronted with a predatory threat and can also
      lead to an earlier return to pre-threat levels of playfulness when that threat
      becomes less immediate.

PMID- 19766678
TI  - Nerve growth factor attenuates 2-deoxy-d-glucose-triggered endoplasmic reticulum
      stress-mediated apoptosis via enhanced expression of GRP78.
AB  - The glucose analog 2-deoxy-d-glucose (2DG) depletes cells of glucose. Inhibition
      of glycosylation caused by glucose depletion induces endoplasmic reticulum (ER)
      stress with subsequent apoptosis. Glucose-regulated protein 78 (GRP78) is a
      molecular chaperone that acts within the ER. During ER stress, GRP78 expression
      is induced as part of the unfolded protein response (UPR). We found that nerve
      growth factor (NGF) prevented 2DG-triggered ER stress-mediated apoptosis, but not
      the induction of GRP78 expression, in PC12 cells. Surprisingly, GRP78 expression
      was further up-regulated when NGF was added to 2DG-treated PC12 cells. When a
      specific inhibitor of phosphatidylinositol 3-kinase (PI3-K), LY294002, was added
      to 2DG plus NGF-treated cells, both the effects of NGF on 2DG-induced apoptosis
      and GRP78 expression were significantly diminished. In addition, versipelostatin
      (VST), a specific inhibitor of GRP78 expression, and small interfering RNA
      (siRNA) against GRP78 mRNA also decreased both the effects of NGF on 2DG-induced
      apoptosis and GRP78 expression. RT-PCR and Western blot analyses revealed that
      enhanced production of nuclear p50 ATF6, but not spliced XBP1, mainly contributed
      to the NGF-induced enhancement of GRP78 expression in 2DG-treated cells. These
      results suggest that the NGF-activated PI3-K/Akt signaling pathway plays a
      protective role against ER stress-mediated apoptosis via enhanced expression of
      GRP78 in PC12 cells.

PMID- 19766679
TI  - Targeted transfection increases siRNA uptake and gene silencing of primary
      endothelial cells in vitro--a quantitative study.
AB  - Applications of small-interfering RNA (siRNA) call for specific and efficient
      delivery of siRNA into particular cell types. We developed a novel, non-viral
      targeting system to deliver siRNA specifically into inflammation-activated
      endothelial cells. This was achieved by conjugating the cationic amphiphilic
      lipid SAINT to antibodies recognizing the inflammatory cell adhesion molecule E
      selectin. These anti-E-selectin-SAINT lipoplexes (SAINTarg) maintained antigen
      recognition capacity of the parental antibody in vitro, and ex vivo in human
      kidney tissue slices subjected to inflammatory conditions. Regular SAINT mediated
      transfection resulted in efficient gene silencing in human microvascular
      endothelial cells (HMEC-1) and conditionally immortalized glomerular endothelial
      cells (ciGEnC). However, primary human umbilical vein endothelial cells (HUVEC)
      transfected poorly, a phenomenon that we could quantitatively correlate with a
      cell-type specific capacity to facilitate siRNA uptake. Importantly, SAINTarg
      increased siRNA uptake and transfection specificity for activated endothelial
      cells. Transfection with SAINTarg delivered significantly more siRNA into
      activated HUVEC, compared to transfection with non-targeted SAINT. The enhanced
      uptake of siRNA was corroborated by improved silencing of both gene- and protein
      expression of VE-cadherin in activated HUVEC, indicating that SAINTarg delivered
      functionally active siRNA into endothelial cells. The obtained results
      demonstrate a successful design of a small nucleotide carrier system with
      improved and specific siRNA delivery into otherwise difficult-to-transfect
      primary endothelial cells, which in addition reduced considerably the amount of
      siRNA needed for gene silencing.

PMID- 19766680
TI  - Peptide nanocarriers for intracellular delivery of photosensitizers.
AB  - Previously we have shown that recombinantly produced amphiphilic oligopeptides
      with amino acid sequence Ac-Ala-Ala-Val-Val-Leu-Leu-Leu-Trp-Glu-Glu spontaneously
      assemble into nano-sized vesicles with an average diameter of 120 nm. Moreover,
      peptide vesicles could be stabilized by introducing multiple cysteine residues
      within the hydrophobic domain of these amphiphilic oligopeptides, allowing the
      formation of intermolecular disulfide bridges. In this study, the cellular
      association and internalization of peptide vesicles were assessed. Flow cytometry
      and confocal laser-scanning microscopy showed that peptide vesicles were
      internalized by cells predominantly via adsorptive macropinocytosis. Furthermore,
      the potential of these peptide vesicles as delivery system for photosensitizers
      was explored. Water-insoluble phthalocyanines could be quantitatively entrapped
      within the hydrophobic domains of these peptide vesicles. Confocal laser-scanning
      microscopy analysis showed that internalized peptides co-localized with the
      phthalocyanine, suggesting that peptide vesicles are internalized in their intact
      form. Upon illumination, the phthalocyanine-containing peptide vesicles showed an
      active photodynamic response towards the cells leading to effective cell killing.
      In contrast, the free phthalocyanine or empty peptide vesicles did not show any
      cytotoxicity. In conclusion, this is the first demonstration that peptide
      vesicles show promise as delivery systems for photosensitizers to be used in
      photodynamic therapy.

PMID- 19766681
TI  - Towards elucidation of the drug release mechanism from compressed hydrophilic
      matrices made of cellulose ethers. II. Evaluation of a possible swelling
      controlled drug release mechanism using dimensionless analysis.
AB  - A swelling-controlled mechanism, based on the simple fitting of drug release data
      to a power law, is frequently invoked to explain deviations from Fickian
      diffusion. Therefore, the purpose of this work was to evaluate whether such a
      mechanism is possible in the case of compressed hydrophilic matrices made of
      cellulose ethers, using parameters that were independently obtained, either in
      Part I (Ferrero et al.,) or in the present study. The derivatives used were
      hydroxypropyl methyl celluloses, hydroxyethyl celluloses and hydroxypropyl
      celluloses of varying molecular mass. We investigated polymer chain relaxation
      (by mechanical testing and oscillatory rheology), the release characteristics of
      the model drug sodium salicylate, as well as the swelling behavior of the
      compressed tablets (front movements and water uptake). Assessment of a possible
      swelling-controlled release (relaxation-controlled, penetrant-activated)
      mechanism was based on the use of the Deborah number, De, and that of the
      swelling interface number, Sw. Two extreme polymer fractions were considered for
      the evaluation of De and Sw, namely those fractions that were assumed to be
      present at the swelling front and at the eroding front. Analysis of drug release
      data using the Korsmeyer-Peppas model resulted in diffusional exponent n values
      that were consistently greater than 0.44 (for the cylindrical geometry used
      here), which could thus indicate anomalous (coupled diffusion-relaxation) drug
      transport behavior. However, from the observed De values<<1 (at both fronts),
      which are indicative of water Fickian diffusion in the rubbery polymer matrix,
      and the Sw values>>1 (at the swelling front), which correspond to drug Fickian
      diffusion, we infer that a swelling-controlled drug release mechanism should be
      dismissed for such water-soluble hydrophilic cellulose ethers, i.e. polymer chain
      relaxation is not the rate-limiting step in the drug release process from this
      type of hydrophilic polymer. In fact, Sw values close to unity were calculated
      for the erosion front, but this is not a sufficient criterion for a swelling
      controlled release mechanism. In addition, the dimensionless numbers calculated
      for the erosion front should be considered cautiously and conservatively since
      relaxation of the macromolecules is very unlikely to still occur when the latter
      are in the process of detaching from the polymer matrix. In addition, it was
      experimentally confirmed from the front positions that erosion is the phenomenon
      operating with this type of swellable polymer, concomitantly with Fickian
      diffusion. As surface erosion follows the same kinetics as the relaxational
      process, the coupled diffusion/erosion mechanism accounts for diffusional
      exponent n values greater than 0.50, 0.45 and 0.43 for the slab (film), the
      cylindrical (disk) and the spherical geometry, respectively, as calculated from
      drug release data using the power law equation.

PMID- 19766682
TI  - The structure of bioactive analogs of the N-terminal region of gastrin-17.
AB  - Gastrin-17 (G17) processing intermediates bind to non-CCK receptors which mediate
      growth of the colonic mucosa but also the formation and development of colonic
      cancers. In previous studies, we removed the C-terminal region of G17 to form
      G17(1-12) and considerably shorter C-terminally amidated and non-amidated
      analogs. Peptides as short as G17(1-4) continued to bind to a single site on DLD
      1 human colonic carcinoma cells, while only the G17(1-6)-NH(2) and G17(1-12)
      peptides retained the ability to activate the receptor and stimulate cell
      proliferation in vitro. In this report, we studied the structure of these
      analogs, using a combination of ECD and VCD spectroscopy and replica exchange
      molecular dynamics (REMD) simulations in water, TFE, and membrane-mimicking
      environments, in order to determine preferred conformations that may have
      importance in promoting the biological activities. Mostly random meander
      structures, punctuated by a beta-turn at residues 1-4, were found in most
      peptides by REMD simulations. G17(1-3)-NH(2), which cannot form a beta-turn,
      failed to bind the non-CCK receptor, suggesting the importance of this feature
      for binding. Additionally, the beta-turn appeared more frequently in longer
      sequences, possibly explaining the higher affinity of the non-CCK receptor for
      these peptides seen previously. Finally, C-terminally amidated peptides generally
      showed greater formation of turn structure than their non-amidated counterparts
      as shown by ECD spectra, suggesting the importance of peptide length in
      stabilizing turn structure in N-terminal sequences, and perhaps explaining the
      ability of G17(1-6)-NH(2) to activate the non-CCK receptor where as the non
      amidated G17(1-6) and shorter peptides do not.

PMID- 19766683
TI  - Application of the "threshold of toxicological concern" to derive tolerable
      concentrations of "non-relevant metabolites" formed from plant protection
      products in ground and drinking water.
AB  - Limits for tolerable concentrations of ground water metabolites ("non-relevant
      metabolites" without targeted toxicities and specific classification and
      labeling) derived from active ingredients (AI) of plant protection products
      (PPPs) are discussed in the European Union. Risk assessments for "non-relevant
      metabolites" need to be performed when concentrations are above 0.75 microg/L.
      Since oral uptake is the only relevant exposure pathway for "non-relevant
      metabolites", risk assessment approaches as used for other chemicals with
      predominantly oral exposure in humans are applicable. The concept of "thresholds
      of toxicological concern" (TTC) defines tolerable dietary intakes for chemicals
      without toxicity data and is widely applied to chemicals present in food in low
      concentrations such as flavorings. Based on a statistical evaluation of the
      results of many toxicity studies and considerations of chemical structures, the
      TTC concept derives a maximum daily oral intake without concern of 90
      microg/person/day for non-genotoxic chemicals, even for those with appreciable
      toxicity. When using the typical exposure assessment for drinking water
      contaminants (consumption of 2L of drinking water/person/day, allocation of 10%
      of the tolerable daily intake to drinking water), a TTC-based upper concentration
      limit of 4.5 microg/L for "non-relevant metabolites" in ground/drinking water is
      delineated. In the present publication it has been evaluated, whether this value
      would cover all relevant toxicities (repeated dose, reproductive and
      developmental, and immune effects). Taking into account, that after evaluation of
      specific reproduction toxicity data from chemicals and pharmaceuticals, a value
      of 1 microg/kgbw/day has been assessed as to cover developmental and reproduction
      toxicity, a TTC value of 60 microg/person/day was assessed as to represent a safe
      value. Based on these reasonable worst case assumptions, a TTC-derived threshold
      of 3 microg/L in drinking water is derived. When a non-relevant metabolite is
      present in concentration below 3 microg/L, animal testing for toxicity is not
      considered necessary for a compound-specific risk assessment since the
      application of the TTC covers all relevant toxicities to be considered in such
      assessment and any health risk resulting from these exposures is very low.

PMID- 19766684
TI  - Risk and safety assessment of exogenous human brain natriuretic peptide in
      cynomolgus monkeys (Macaca fascicularis)--a subchronic study.
AB  - Safety evaluation of synthetic human brain natriuretic peptide (shBNP) was
      carried out in cynomolgus monkeys (Macaca fascicularis) by 2-week intravenous
      toxicity studies. System exposure was also assessed throughout the whole
      administration. Three test groups received doses of 432, 1440 and 4320
      microg/kg/day of shBNP, with a high infusion rate of 36 mL/kg/hr for 30 min
      compared to the clinical protocol of continuous infusion over 24h. Commercially
      available recombinant human brain natriuretic peptide (rhBNP) of 1440
      microg/kg/day was used as positive control. The 2-week repeated intravenous doses
      of shBNP resulted in reversible increased serum LDH and CPK in monkeys receiving
      1440 and 4320 microg/kg/day dose with no pertinent histopathological changes.
      Some changes related to the pharmacologic effects of BNP including hypotension
      was observed after administration. No treatment-related mortalities or renal
      dysfunction were found. Controversy about the safety issue of BNP as an exogenous
      hormone concerning ventricular remodeling and myocardial cell apoptosis, coupled
      with our results, were also discussed. The no-observed-adverse-effect level
      (NOAEL) was considered to be 432 microg/kg /day, which is about 20 times higher
      than the commonly used clinical dose. The results of the present study advocate
      the safety of shBNP in cynomolgus monkeys at levels used in the study.

PMID- 19766685
TI  - Tools for the prioritization of substances on the Domestic Substances List in
      Canada on the basis of hazard.
AB  - A precedent setting legislative mandate under the Canadian Environmental
      Protection Act 1999 to establish priorities for assessment based on systematic
      consideration of all of the approximately 23,000 Existing Chemicals in Canada
      required the development and refinement of methodology in a number of important
      areas. This included development of simple and complex exposure and hazard tools
      for priority setting which draw maximally and efficiently on available data to
      systematically identify substances that are highest priorities in relation to
      their potential to cause adverse effects on the general population. The
      hierarchical approach in the simple and complex hazard tools described here
      efficiently and effectively sets substances aside as non-priorities, or
      prioritizes them for consideration additionally in assessment. The hazard tools
      efficiently incorporate previous work, contributing to consistency
      internationally, and involve hierarchical consideration of sources of information
      based on their relative weighting. They are health protective, based on their
      incorporated degree of conservatism, and provide direction for additional
      assessment for substances deemed to be priorities. Although designed for
      prioritization of Existing Substances in Canada, these tools have potential for
      broader application in other national and international programs to provide focus
      and increase efficiency in human health risk assessment.

PMID- 19766686
TI  - Remission of schizophrenia psychosis and strong reduction of obsessive-compulsive
      disorder after adding clozapine to aripiprazole.

PMID- 19766687
TI  - Late-onset cholestatic hepatitis induced by olanzapine in a patient with
      schizophrenia.

PMID- 19766688
TI  - Photoprotective potential of emulsions formulated with Buriti oil (Mauritia
      flexuosa) against UV irradiation on keratinocytes and fibroblasts cell lines.
AB  - Considering the belief that natural lipids are safer for topical applications and
      that carotenoids are able to protect cells against photooxidative damage, we have
      investigated whether topical creams and lotions, produced with Buriti oil and
      commercial surfactants, can exert photoprotective effect against UVA and UVB
      irradiation on keratinocytes and fibroblasts. Cell treatment was divided into two
      steps, prior and after exposition to 30 min of UVA plus UVB radiation or to 60
      min of UVA radiation. Emulsions prepared with ethoxylated fatty alcohols as
      surfactants and containing alpha-tocopherol caused phototoxic damage to the
      cells, especially when applied prior to UV exposure. Damage reported was due to
      prooxidant activity and phototoxic effect of the surfactant. Emulsions prepared
      with Sorbitan Monooleate and PEG-40 castor oil and containing panthenol as active
      ingredient, were able to reduce the damages caused by radiation when compared to
      non-treated cells. When the two cell lines used in the study were compared,
      keratinocytes showed an increase in cell viability higher than fibroblasts. The
      Buriti oil emulsions could be considered potential vehicles to transport
      antioxidants precursors and also be used as adjuvant in sun protection,
      especially in after sun formulations.

PMID- 19766689
TI  - Protection against free radicals (UVB irradiation) of a water-soluble enzymatic
      extract from rice bran. Study using human keratinocyte monolayer and
      reconstructed human epidermis.
AB  - The antioxidant capacity of a water-soluble enzymatic extract from rice bran
      (EERB) has been tested in two cell models: keratinocyte monolayers and human
      reconstructed epidermis. Cells were incubated in culture medium in presence of
      different amounts of EERB and were UVB irradiated. Cell population assessment
      (MTT assay) and MDA (malonaldehyde) production were evaluated. The EERB did not
      induce cytotoxic effect for concentrations inferior or equal to 100 microg/mL.
      Human keratinocyte monolayers were protected of irradiation preventing 33% the
      lipid peroxidation process at concentration of 10 microg/ml of EEBR. In
      reconstructed human epidermis, 100 microg/mL decreased lipid peroxidation process
      by 44% (p<0.01) with regards to irradiated negative control. This effect was
      comparable to that of vitamin E at 600 microg/mL. Our data indicate that EERB is
      potentially able to efficiently counteract UVB-induced response. The EERB,
      diluted at 10% with water has very good skin compatibility. This product showed a
      sun protection factor of 4.8+/-0.3. Thus we can propose EERB as a useful natural
      standardized extract in skin photoprotection with promising applications in the
      field of dermatology.

PMID- 19766690
TI  - Total mercury determination in different tissues of broiler chicken by using
      cloud point extraction and cold vapor atomic absorption spectrometry.
AB  - A cloud point extraction (CPE) method has been developed for the determination of
      total mercury (Hg) in different tissues of broiler chicken by cold vapor atomic
      absorption spectrometry (CVAAS). The broiler chicken tissues (leg, breast, liver
      and heart) were subjected to microwave assisted digestion in a mixture of nitric
      acid and hydrogen peroxide (2:1 ratio), prior to preconcentration by CPE. Various
      parameters such as the amount of ammonium O,O-diethyldithiophosphate (DDTP),
      concentrations of Triton X-114, equilibrium temperature, time and centrifugation
      have been studied in order to find the best conditions for the determination of
      mercury. For validation of proposed method a certified reference material, DORM-2
      was used. No significant difference p>0.05 was observed between the experimental
      results and the certified values of CRM (paired t-test). The limit of detection
      and quantitation obtained under the optimal conditions were 0.117 and 0.382
      microg/kg, respectively. The accumulation of Hg in different tissues were found
      in the order of, liver>muscles>heart. The concentration of Hg in chicken tissues
      were found in the range of 1.57-2.75, 1.40-2.27, 1.55-4.22, and 1.39-2.61
      microg/kg in leg, breast, liver and heart, respectively.

PMID- 19766691
TI  - Curcumin inhibits phorbol myristate acetate (PMA)-induced MCP-1 expression by
      inhibiting ERK and NF-kappaB transcriptional activity.
AB  - Monocyte chemoattractant protein-1 (MCP-1) is a potent mediator of macrophage
      migration and therefore, plays an essential role in early events of inflammation.
      In the present study, we show the protein kinase C activator, phorbol myristate
      acetate (PMA), potently induced mRNA expression and secretion of the C-C
      chemokine MCP-1 in U937 cells. We found that curcumin, a natural biologically
      active compound extracted from rhizomes of Curcuma species, significantly
      inhibited the PMA-induced increase in MCP-1 expression and secretion. These
      effects of curcumin are dose dependent and correlate with the suppression of MCP
      1 mRNA expression levels. Curcumin inhibited PMA-mediated activation of
      extracellular signal-regulated kinase (ERK) and NF-kappaB transcriptional
      activity. Therefore, one possible anti-inflammatory mechanism of curcumin may be
      to inhibit the secretions of inflammatory MCP-1 chemokine.

PMID- 19766692
TI  - Selective speciation and determination of inorganic arsenic in water, food and
      biological samples.
AB  - A procedure for the speciation of arsenic(III) and arsenic(V) in natural water
      samples has been established in the presented work. Arsenic(III) ions were
      quantitatively recovered on Alternaria solani coated Diaion HP-2MG resin at pH 7,
      while the recoveries of arsenic(V) was below 10%. Arsenic(V) in the mixing
      solution containing As(III) and As(V) was reduced by using KI and L(+) ascorbic
      acid solution, then the procedure was applied to determination of total arsenic.
      Arsenic(V) was calculated as the difference between the total arsenic content and
      As(III) content. The determination of arsenic was performed by using hydride
      generation atomic absorption spectrometry. The influences of some alkali, earth
      alkali and transition metals on the biosorption of arsenic(III) were
      investigated. The preconcentration factor was 35. The detection limits for
      As(III) (N=20, k=3) was found as 11 ng L(-1). The relative standard deviation and
      relative error of the determinations were found to be lower than 7% and 4%,
      respectively. The accuracy of the method was confirmed with certified reference
      materials. The method was successively applied for the determination and
      speciation of inorganic arsenic in water, food and biological samples.

PMID- 19766693
TI  - Experimental and computational approach to the rational monitoring of hydrogen
      bonding interaction of 2-Imidazolidinethione with DNA and guanine.
AB  - The hydrogen-bonding interaction of 2-Imidazolidinethione with DNA and guanine
      has been investigated using UV/vis, circular dichroism, differential pulse
      voltammetry and ab initio chemical mechanic quantum procedures. The bonding
      constant of 2-Imidazolidinethione with DNA was measured by UV/vis spectroscopy
      and is estimated to be 1.4x10(3). In order to prove of hydrogen-bonding
      formation, the bonding constants of 2-Imidazolidinethione with guanine in Tris
      HCl buffer and binary mixture of buffer-acetonitrile were measured. In addition,
      density functional theory calculations, using ab initio methodology at the 6
      31+G(d,p) level and simulating the effect of solvents on interaction by mean of
      the Cosmo Polarizable Continuum Model (CPCM), were performed on the single and
      complex of 2-Imidazolidinethione and guanine molecules. However, we concluded
      that 2-Imidazolidinethione interacted with N(3) of guanine in minor groove of
      DNA.

PMID- 19766694
TI  - Correlations between polyphenolic composition and antioxidant activity of
      Venetian propolis.
AB  - Four propolis samples have been picked up in the Venetian region, from different
      orography and habitative density areas with the purpose to: (i) evaluate
      propolis' antioxidant activity, measured by inhibition of lipid peroxidation;
      (ii) determine the polyphenolic components--flavonoids and caffeic acid
      derivatives--which give antioxidant activity to propolis; (iii) verify the
      potential correlations between antioxidant activity, polyphenolic content, that
      has been determined by Folin-Ciocalteu, enzymatic, DPPH quenching, TEAC-like
      assays, and spectroscopic characteristics of propolis and (iv) correlate chemical
      structure and antioxidant efficacy of each of the major components. The possible
      localization of the lipophylic components of propolis into the phospholipidic
      bilayer by thermal analysis (DSC) and spin label EPR techniques has also been
      investigated.

PMID- 19766695
TI  - Impaired mitochondrial energy metabolism and kinetic properties of cytochrome
      oxidase following acute aluminium phosphide exposure in rat liver.
AB  - The present study was designed with an aim to analyze the effect of acute
      aluminium phosphide (ALP) exposure (10mg/kg b.wt, intragastrically) on the
      kinetic characteristics of cytochrome oxidase and energy metabolism in male
      Wistar rat liver mitochondria. Liver mitochondrial preparations from ALP-treated
      rats exhibited significant decrease (66%) in the activity of cytochrome oxidase
      suggesting that there was a decrease in the catalytic efficiency of the active
      oxidase molecules on ALP treatment. The decreased activity of cytochrome oxidase
      with altered NADH and succinic dehydrogenase activities might have contributed
      towards a significant decline in state 3 and state 4 respiration as observed.
      These alterations in the electron transport chain complexes in turn adversely
      affected the ATP synthesis rate as well as ATP levels in the mitochondria
      isolated from treated rats. The alterations in the respiratory chain, was
      followed by enhanced lipid peroxidation in rat liver mitochondria which might
      have further contributed to change in the fluidity of membrane as depicted by
      decreased fatty acid content of liver mitochondria. However, no significant
      change was observed in cholesterol and phospholipids content in our study. The
      present study thus highlights the significance of altered mitochondrial
      respiratory chain functions and membrane integrity after acute ALP exposure.

PMID- 19766696
TI  - Well-trained, healthy triathletes experience no adverse health risks regarding
      oxidative stress and DNA damage by participating in an ultra-endurance event.
AB  - Also physical exercise in general is accepted to be protective, acute and
      strenuous exercise has been shown to induce oxidative stress. Enhanced formation
      of free radicals leads to oxidation of macromolecules and to DNA damage. On the
      other hand ultra-endurance events which require strenuous exercise are very
      popular and the number of participants is continuously increasing worldwide.
      Since only few data exists on Ironman triathletes, who are prototypes of ultra
      endurance athletes, this study was aimed at assessing the risk of oxidative
      stress and DNA damage after finishing a triathlon and to predict a possible
      health risk. Blood samples of 42 male athletes were taken 2 days before, within
      20 min after the race, 1, 5 and 19 days post-race. Oxidative stress marker
      increased only moderately after the race and returned to baseline after 5 days.
      Marker of DNA damage measured by the SCGE assay with and without restriction
      enzymes as well as by the sister chromatid exchange assay did either show no
      change or deceased within the first day after the race. Due to intake during the
      race and the release by the cells plasma concentrations of vitamin C and alpha
      tocopherol increased after the event and returned to baseline 1 day after. This
      study indicates that despite a temporary increase in some oxidative stress
      markers, there is no persistent oxidative stress and no DNA damage in response to
      an Ironman triathlon in trained athletes, mainly due to an appropriate
      antioxidant intake and general protective alterations in the antioxidant defence
      system.

PMID- 19766697
TI  - Suicide neurobiology.
AB  - In this review, we examine the history of the neurobiology of suicide, as well as
      the genetics, molecular and neurochemical findings in suicide research. Our
      analysis begins with a summary of family, twin, and adoption studies, which
      provide support for the investigation of genetic variation in suicide risk. This
      leads to an overview of neurochemical findings restricted to neurotransmitters
      and their receptors, including recent findings in whole genome gene expression
      studies. Next, we look at recent studies investigating lipid metabolism, cell
      signalling with a particular emphasis on growth factors, stress systems with a
      focus on the role of polyamines, and finally, glial cell pathology in suicide. We
      conclude with a description of new ideas to study the neurobiology of suicide,
      including subject-specific analysis, protein modification assessment,
      neuroarchitecture studies, and study design strategies to investigate the complex
      suicide phenotype.

PMID- 19766698
TI  - Mechanisms of chromosomal rearrangements in solid tumors: the model of papillary
      thyroid carcinoma.
AB  - Thyroid cancer, and its most common type, papillary carcinoma, frequently have
      chromosomal rearrangements and therefore represent a good model for the
      understanding of mechanisms of chromosomal rearrangements in solid tumors.
      Several types of rearrangement known to occur in thyroid cancer, including
      RET/PTC, NTRK1 and BRAF/AKAP9, are more common in radiation-associated thyroid
      tumors and RET/PTC can be induced experimentally by exposing human thyroid cells
      to ionizing radiation. In this review, the molecular mechanisms of generation of
      RET/PTC and other chromosomal rearrangements are discussed, with the emphasis on
      the role of nuclear architecture and interphase gene proximity in the generation
      of intrachromosomal rearrangements in thyroid cells.

PMID- 19766699
TI  - Sialic acid, homocysteine and CRP: potential markers for dementia.
AB  - To investigate whether sialic acid could discriminate between healthy age matched
      controls and patients with dementias of the Alzheimer's type (AD), and pure
      vascular dementia (VaD). 27 patients and 51 controls were administered the Mini
      Mental State Examination (MMSE) and had blood analyzed for levels of total sialic
      acid, total homocysteine (tHcy), and C-reactive protein (CRP). Significant
      differences were found between the mean MMSE scores for patients with dementia
      compared with controls. Sialic acid levels were significantly higher in patients
      with AD compared with controls and homocysteine levels were higher in VaD. Sialic
      acid levels discriminated between patients with dementia of the Alzheimer's type
      and healthy controls only. The MMSE could discriminate between controls and
      patients with dementia but not between the subtypes and homocysteine was
      significant for patients with VaD.

PMID- 19766700
TI  - Association and expression study of synapsin III and schizophrenia.
AB  - The synapsin III gene, SYN3, which belongs to the family of synaptic vesicle
      associated proteins, has been implicated in the modulation of neurotransmitter
      release and in synaptogenesis, suggesting a potential role in several
      neuropsychiatric diseases. The human SYN3 gene is located on chromosome 22q12-13,
      a candidate region implicated in previous linkage studies of schizophrenia.
      However, association studies of SYN3 and schizophrenia have produced inconsistent
      results. In this study, four SYN3 SNPs (rs133945 (-631 C>G), rs133946 (-196 G>A),
      rs9862 and rs1056484) were tested in three sets of totally 3759 samples that
      comprise 655 affected subjects and 626 controls in the Irish Case-Control Study
      of Schizophrenia (ICCSS), 1350 samples incorporating 273 pedigrees in the Irish
      Study of High Density Schizophrenia Families (ISHDSF), and 564 unrelated
      schizophrenia patients and 564 healthy individuals in a Chinese case-control
      sample. The expression levels of SYN3 in schizophrenic patients and unaffected
      controls were compared using postmortem brain cDNAs provided by the Stanley
      Medical Research Institute (SMRI). There was no significant association in either
      the Irish or Chinese case-control samples, nor in the combined samples.
      Consistent with this finding, we did not find any significant difference in
      allele or haplotype frequencies when we used the pedigree disequilibrium test to
      analyze the Irish family sample. In the expression studies, no significant
      difference (p=0.507) was observed between patients and controls. Both the
      association studies and expression studies didn't support a major role for SYN3
      in the susceptibility of schizophrenia in Irish and Chinese populations.

PMID- 19766701
TI  - Kinetic characterization of recombinant mouse retinal dehydrogenase types 3 and 4
      for retinal substrates.
AB  - BACKGROUND: Retinal dehydrogenases (RALDHs) catalyze the dehydrogenation of
      retinal into retinoic acids (RAs), which are required for embryogenesis and
      tissue differentiation. This study sought to determine the detailed kinetic
      properties of 2 mouse RALDHs, namely RALDH3 and 4, for retinal isomer substrates,
      to better define their specificities in RA isomer synthesis. METHODS: RALDH3 and
      4 were expressed in Escherichia coli as His-tagged proteins and affinity
      purified. Enzyme kinetics were performed with retinal isomer substrates. The
      enzymatic products were analyzed by high pressure liquid chromatography. RESULTS:
      RALDH3 oxidized all-trans retinal with high catalytic efficiency (Vmax/Km=77.9)
      but did not show activity for either 9-cis or 13-cis retinal substrates. On the
      other hand, RALDH4 was inactive for all-trans retinal substrate, exhibited high
      activity for 9-cis retinal oxidation (Vmax/Km=27.4), and oxidized 13-cis retinal
      with lower catalytic efficiency (Vmax/Km=8.24). beta-ionone, a potent inhibitor
      of RALDH4 activity, suppressed 9-cis and 13-cis retinal oxidation competitively
      with inhibition constants of 0.60 and 0.32, respectively, but had no effect on
      RALDH3 activity. The divalent cation MgCl2 activated 13-cis retinal oxidation by
      RALDH4 by 3-fold, did not significantly influence 9-cis retinal oxidation, and
      slightly activated RALDH3 activity. CONCLUSIONS: These data extend the kinetic
      characterization of RALDH3 and 4, providing their specificities for retinal
      isomer substrates. GENERAL SIGNIFICANCE: The kinetic characterization of RALDHs
      should give useful information in determining amino acid residues that are
      involved in the specificity for retinal isomers and on the role of these enzymes
      in the synthesis of RAs in specific tissues.

PMID- 19766702
TI  - The subjective value of delayed and probabilistic outcomes: Outcome size matters
      for gains but not for losses.
AB  - The subjective value of a reward (gain) is related to factors such as its size,
      the delay to its receipt and the probability of its receipt. We examined whether
      the subjective value of losses was similarly affected by these factors in 128
      adults. Participants chose between immediate/certain gains or losses and larger
      delayed/probabilistic gains or losses. Rewards of $100 were devalued as a
      function of their delay ("discounted") relatively less than $10 gains while
      probabilistic $100 rewards were discounted relatively more than $10 rewards.
      However, there was no effect of outcome size on discounting of delayed or
      probabilistic losses. For delayed outcomes of each size, the degree to which
      gains were discounted was positively correlated with the degree to which losses
      were discounted, whereas for probabilistic outcomes, no such correlation was
      observed. These results suggest that the processes underlying the subjective
      valuation of losses are different from those underlying the subjective valuation
      of gains.

PMID- 19766703
TI  - Rapid simultaneous determination of apoptosis, necrosis, and viability in sulfur
      mustard exposed HaCaT cell cultures.
AB  - Sulfur mustard (SM; bis(2-chloroethyl)sulphide; HD) is a blister inducing agent
      causing DNA damage and subsequently, cell death, mostly by apoptosis in basal
      keratinocytes. Despite intensive investigations on the cellular mechanism, there
      are, as of now, no causal therapeutics to prevent or antagonize SM-related damage
      to cells and tissues. In order to develop treatment strategies against
      vesication, it is important to distinguish apoptosis from necrosis in SM treated
      human keratinocytes. DNA fragmentation is a hallmark of apoptosis and regulated
      by a cascade of enzymes (endonucleases, DNase I, NUC 18), which finally cut the
      chromatin into specific formations of 180-200 base pairs, the nucleosomes. A
      feasible way to monitor apoptosis is the detection of nucleosomes by means of the
      Cell Death Detection ELISA(plus) (CDDE). In contrast, during necrosis DNA
      fragmentation is at random and delivers larger fragments, which therefore are
      significantly less in number and predominantly occur in cell culture supernatant.
      To monitor necrosis, we measured the release of intracellular adenylate kinase
      (AK) into cell culture supernatant by means of the ToxiLight Bioluminescence
      Assay (TL). With combination of the Cell Death Detection ELISA(plus) and the
      ToxiLight Bioluminescence Assay, we acquired more comprehensive information on
      cell survival and mechanisms of cell death, following an SM exposure. To validate
      the assay we tested common apoptosis- and necrosis-inducing agents like SM 300
      microM for 30 min, Lewisite (L) 60 microM for 5 min and Triton X-100 0.1%. The
      results show that it is possible to differentiate between the two modes of cell
      death and to quantify their extent. This assay is highly effective in quantifying
      apoptosis and necrosis caused by cytotoxic agents and in estimating protective
      effects of potential active pharmaceutical ingredients.

PMID- 19766704
TI  - Palytoxin toxicity after acute oral administration in mice.
AB  - The acute oral toxicity of palytoxin (PLTX), a highly toxic compound associated
      with seafood intoxication in tropical and subtropical areas, was investigated in
      mice. After gavage administration (300-1697 microg/kg) to groups of five female
      CD-1 mice, signs of toxicity and lethality were recorded for 24 h. The LD(50) was
      767 microg/kg (95% confidence limits: 549-1039 microg/kg) and the main symptoms
      observed were scratching, jumping, respiratory distress and paralysis.
      Hematoclinical analyses showed increased levels of creatine phosphokinase and
      lactate dehydrogenase at doses of 600 microg/kg and above, and aspartate
      transaminase at 848 microg/kg and above. Histological analysis revealed acute
      inflammation of the forestomach in mice surviving up to 24h after administration
      (424-1200 microg/kg). Other histological alterations were observed in the liver
      and pancreas, while cardiac and skeletal muscle cells revealed only
      ultrastructural alterations visible by transmission electron microscopy.
      Ultrastructural and hematoclinical findings suggest an involvement of skeletal
      and/or cardiac muscle as targets of PLTX, according to the observed human
      symptoms. A NOEL of 300 microg/kg can be estimated from this acute oral toxicity
      study.

PMID- 19766705
TI  - Chlorophenols and chlorocatechols induce apoptosis in human lymphocytes (in
      vitro).
AB  - In this work the effect of 2,4,5-trichlorophenol (2,4,5-TCP), pentachlorophenol
      (PCP), 4,6-dichloroguaiacol (4,6-DCG), tetrachloroguaiacol (TeCG), 4,5
      dichlorocatechol (4,5-DCC) and tetrachlorocatechol (TeCC) on the induction of
      apoptosis in human peripheral blood lymphocytes was examined. The analysis of the
      changes in mitochondrial transmembrane potential (DeltaPsi(m)) was performed
      using JC-9 fluorescent probe. It was noted that all the compounds studied
      (excluding 4,6-DCG) in a dose-dependent manner (0.2-25 ppm) increased the number
      of cells, which were characterized by the DeltaPsi(m) reduction, with the
      strongest effect observed for TeCG and TeCC. Moreover, fluorimetric assay of the
      caspase-3 activity revealed that 2,4,5-TCP, chlorocatechols and TeCG in the range
      of the concentrations of 1-50 ppm increased the caspase-3 expression, whereas PCP
      in its highest concentration of 50 ppm decreased the activity of this enzyme. It
      was also noted that the caspase-3 activity was the most strongly induced by
      tetrachlorocatechols, particularly by TeCC. The analysis of YO-PRO-1
      iodide/propidum iodide staining revealed that TeCC, the most strongly increased
      the number of apoptotic cells at 5 and 25 ppm, whereas at a dose of 100 ppm the
      strongest effect on apoptosis induction was observed for 2,4,5-TCP.

PMID- 19766706
TI  - Study of critical points of drugs with different solubilities in hydrophilic
      matrices.
AB  - Hydrophilic matrices are one of the most popular controlled release systems in
      the world. It is well known that drug solubility increases the osmotic stress in
      hydrophilic matrices, resulting in higher swelling through the creation of
      microcavities and influencing the release rate. Drug solubility also affects the
      drug release mechanism, favouring the diffusion against the erosion mechanism.
      Nevertheless it has not been studied whether this can modify the critical points
      of the hydrophilic matrices. The objective of the present work is to estimate the
      excipient percolation threshold in HPMC K4M hydrophilic matrices containing
      acetaminophen, theophiline and ranitidine.HCl, and to study the influence of the
      drug solubility on the excipient percolation threshold. Dissolution assays were
      performed using the paddle method. Water uptake was examined using the modified
      Enslin apparatus. In order to estimate the excipient percolation threshold, the
      behaviour of the kinetic parameters versus the excipient volume fraction plus
      initial porosity, was studied. The excipient percolation thresholds were situated
      between 24.8-25.8, 14.7-18.4 and around 31.2% (v/v) HPMC in theophiline,
      ranitidine.HCl and acetaminophen matrices, respectively. On the other hand, using
      these and some previously reported values no relation has been found between drug
      solubility and excipient percolation threshold in hydrophilic matrices.

PMID- 19766707
TI  - Practical application to time indicator of a novel white film formed by
      interaction of calcium salts with hydroxypropyl methylcellulose.
AB  - We have found that a cast film forms a white film when an aqueous solution
      comprising hydroxypropyl methylcellulose (HPMC) and calcium salts such as calcium
      lactate pentahydrate (CLP) and calcium chloride (CaCl(2)) is used. In contrast,
      the obtained white film was transformed into a transparent film by the addition
      of purified water. The transformation time for the change from the white film to
      the transparent film was dependent on film thickness. The relationship between
      the transformation time and the film thickness was significantly correlated, and
      it was found that the white film could be adaptable as time indicator. The
      formation of a white film comprising HPMC and calcium salts was strongly
      dependent on temperature conditions. The objective of the present study is to
      investigate the mechanism of the formation of this white film because of the
      interaction between HPMC and calcium salts. The DSC and XRPD results indicate
      that the calcium salts affect the HPMC polymer phase in the cast film comprising
      HPMC and calcium salts. By carrying out attenuated total reflection Fourier
      transform infrared (ATR FT-IR) analysis, we found that the white film could be
      formed by the calcium salts affecting the region associated with the C-O-C, C-O,
      and CH(3) stretching of the HPMC polymer phase.

PMID- 19766708
TI  - Delivery of fullerene-containing complexes via microgel swelling and shear
      induced release.
AB  - The absorption and release of poly(vinylpyrrolidone)-fullerene C60 complexes
      (PVP/C60) from a model microgel is studied. A dry microgel based on a chemically
      cross-linked sodium polyacrylate was swollen in the aqueous solutions of
      complexes which were afterwards released under shear stress. First, gel swelling
      degree in static conditions in the excess of PVP/C60 solutions was studied: the
      degree of swelling decreases with the increase in PVP/C60 concentration. While
      pure PVP is homogeneously distributed between the gel and the surrounding
      solution, a slight concentration of complexes outside the gel was recorded. It
      was attributed to PVP/C60 hydrophobicity leading to the decrease in the
      thermodynamic quality of fullerene-containing solution being gel solvent. The
      release of PVP/C60 solutions induced by shear was studied with counter-rotating
      rheo-optical technique and compared with PVP solution release under the same
      conditions. The amount of solution released depends on polymer concentration and
      shear strain. Contrary to pure PVP solutions in which rate of release decreases
      with the increase in polymer concentration, PVP/C60 complexes are released faster
      when fullerene concentration inside the gel is higher.

PMID- 19766709
TI  - Changes in the expression of insulin-like growth factor 1 variants in the
      postnatal brain development and in neonatal hypoxia-ischaemia.
AB  - Insulin-like growth factor-1 (IGF-1) is a multifunctional peptide of which
      numerous isoforms exist. The predominant form, IGF-1Ea is involved in
      physiological processes while IGF-1Ec (mechano-growth factor, MGF) is expressed
      in response to a different set of stimuli. We have identified specific changes in
      the expression patterns of these IGF-1 variants in brain development in normal
      rats and following neonatal hypoxia-ischaemia (HI). Both IGF-1Ea and IGF-1Ec are
      expressed during normal postnatal brain development, albeit with highly specific
      temporal distributions. In contrast, HI produced increased and prolonged
      expression of the IGF-1Ec isoform only. Importantly, hypoxia alone stimulated the
      expression of IGF-1Ec as well. Thus, IGF-1Ec may play a role in HI pathology.
      Neonatal hypoxia-ischaemia occurs in approximately 1:4000-1:10,000 newborns and
      causes neurological deficits in approximately 75% of those affected.
      Unfortunately, no specific treatment is available. IGF-1 is known to have
      neuroprotective activity and its IGF-1Ec variant appears to be an endogenous
      protective factor in hypoxia-ischaemia. Therefore, IGF-1Ec could potentially be
      developed into a therapeutic modality for the attenuation or prevention of
      neuronal damage in this and related disorders.

PMID- 19766710
TI  - Genome-scale screening and molecular characterization of membrane-bound
      transcription factors in Arabidopsis and rice.
AB  - Controlled proteolytic activation of membrane-bound transcription factors (MTFs)
      is recently emerging as a versatile way of rapid transcriptional responses to
      environmental changes in plants. Here, we report genome-scale identification of
      putative MTFs in the Arabidopsis and rice genomes. The Arabidopsis and rice
      genomes have at least 85 and 45 MTFs, respectively, in virtually all major
      transcription factor families. Of particular interest is the NAC MTFs (designated
      NTLs): there are at least 18 NTLs in Arabidopsis and 5 NTL members (OsNTLs) in
      rice. While the full-size OsNTL forms are associated with the membranes,
      truncated forms lacking the transmembrane domains are detected exclusively in the
      nucleus. Furthermore, transcript levels of the OsNTL genes were elevated after
      treatments with abiotic stresses, supporting their roles in plant stress
      responses. We propose that membrane-mediated transcriptional control is a
      critical component of gene regulatory network that serves as an adaptive strategy
      under unfavorable growth conditions.

PMID- 19766711
TI  - Identifying errors in avian influenza virus gene sequences and implications for
      data usage of public databases.
AB  - Public gene sequence databases have become important research tools to understand
      viruses and other organisms. Evidence suggests that the identifying information
      for some of the sequences in these databases might not belong to the sequences
      they are associated with. We developed two tests to conduct a comprehensive
      analysis of all published sequences of the hemaglutinin and neuramidase genes of
      avian influenza viruses (AIVs) to identify sequences that may have been
      misclassified. One test identified sequence pairs with highly similar nucleotide
      sequences despite a difference of several years between their sampling dates.
      Another test, which was applied to samples sequenced and deposited more than
      once, detected sequences with more nucleotide differences to their own than to
      their closest relatives. All sequences identified as misclassified were further
      traced to relevant publications to assess the likelihood of contamination and
      determine if any conclusions were associated with the use of these sequences. Our
      results suggested that among 4040 published gene sequences examined,
      approximately 0.8% might be misclassified and that publications using these
      sequences may include inaccurate statements. Findings from this report suggest
      that using laboratory-adapted strains and handling multiple samples
      simultaneously increases the risk of contamination. The tests reported here may
      be useful for screening new submissions to public sequence databases.

PMID- 19766712
TI  - Antioxidants change platelet responses to various stimulating events.
AB  - The role of platelets in hemostasis may be influenced by alteration of the
      platelet redox state-the presence of antioxidants and the formation of reactive
      oxygen and nitrogen species. We investigated the effects of two antioxidants,
      resveratrol and trolox, on platelet activation. Trolox and resveratrol inhibited
      aggregation of washed platelets and platelet-rich plasma activated by ADP,
      collagen, and thrombin receptor-activating peptide. Resveratrol was a more
      effective agent in reducing platelet static and dynamic adhesion in comparison
      with trolox. The antioxidant capacity of resveratrol was, however, the same as
      that of trolox. After incubation of platelets with antioxidants, the resveratrol
      intraplatelet concentration was about five times lower than the intracellular
      concentration of trolox. Although both antioxidants comparably lowered hydroxyl
      radical and malondialdehyde production in platelets stimulated with collagen,
      TxB(2) levels were decreased by resveratrol much more effectively than by trolox.
      Cyclooxygenase 1 was inhibited by resveratrol and not by trolox. Our data
      indicate that antioxidants, apart from nonspecific redox or radical-quenching
      mechanisms, inhibit platelet activation also by specific interaction with target
      proteins. The results also show the importance of studying platelet activation
      under conditions of real blood flow in contact with reactive surfaces, e.g.,
      using dynamic adhesion experiments.

PMID- 19766713
TI  - Physical and functional interactions of cyclophilin B with neuronal actin and
      peroxiredoxin-1 are modified by oxidative stress.
AB  - Presynaptic actin was identified as a new Torpedo cyclophilin B partner captured
      in pull-down experiments and by coimmunoprecipitation. The cyclophilin B-actin
      pull-down interaction was insensitive to the blockade of peptidyl cis/trans
      prolyl isomerase and calcineurin activities and to the latrunculin A- and
      jasplakinolide-mediated perturbation of F-actin polymerization. Conversely, it
      was reduced by ATP and stimulated by a low Cu(2+) treatment of synaptosomes and
      by acrolydan-conjugated cyclophilin B. This Cu(2+)-induced stress, in parallel,
      stimulates the formation of GSH adducts with cysteines of synaptosomal actin
      followed by its deglutathionylation and its dimerization in the presence of
      higher Cu(2+) concentrations. The reversibility of the thiol processing of actin
      occurred in the same range of Cu(2+) concentrations that mediated a stronger
      cyclophilin B-actin interaction, suggesting cyclophilin B participation in
      antioxidant processes. Among 2-Cys-peroxiredoxin isoforms, mainly peroxiredoxin-1
      was found in cell bodies and nerve endings. Functionally, both Torpedo and human
      peroxiredoxin-1 were activated in vitro by Torpedo cyclophilin B. Moreover,
      cyclophilin B, like thioredoxins, maintained an H(2)O(2)-dependent peroxidase
      activity of peroxiredoxin-1 in the presence of dithiothreitol. Thus, the
      monocysteinic Torpedo cyclophilin B is able to sustain peroxiredoxin-1 activity
      and might be involved in the presynaptic defense against oxidative stress
      affecting G-actin posttranslational changes and its redox signaling in nerve
      ending compartments.

PMID- 19766714
TI  - Human-specific induction of glutathione peroxidase-3 by proteasome inhibition in
      cardiovascular cells.
AB  - Glutathione peroxidase-3 (GPx-3) is a key antioxidant enzyme in the plasma. GPx-3
      was previously identified as the major antioxidative enzyme that was induced upon
      nontoxic proteasome inhibition in endothelial cells. Here, we investigated the
      determinants of the proteasome inhibitor-induced expression of GPx-3. Nontoxic
      proteasome inhibition massively upregulates GPx-3 RNA and protein in human
      umbilical cord vein cells within 24 h. Surprisingly, induction of GPx-3 was
      species-specific for human cells. The exponential upregulation of GPx-3 is
      mediated by transcriptional activation of the human GPx-3 promoter and, in
      addition, stabilization of GPx-3 mRNA: in reporter gene assays with full-length
      and deleted variants of the human GPx-3 promoter we identified a putative
      antioxidative response element (ARE) as essential and also sufficient for
      transcriptional activation of GPx-3 by proteasome inhibition. However, the ARE
      specific antioxidative transcription factor Nrf2 is not involved in the
      activation of GPx-3. UV-crosslinking using the 3'UTR of GPx-3 revealed an altered
      protein binding pattern in the presence of proteasome inhibitors, thus indicating
      regulation of mRNA stability of human GPx-3. As GPx-3 is secreted into the
      plasma, our data point toward a borderline defense mechanism of endothelial cell
      derived GPx-3 to protect the vasculature from oxidative stress.

PMID- 19766715
TI  - High levels of thioredoxin reductase 1 modulate drug-specific cytotoxic efficacy.
AB  - The selenoprotein thioredoxin reductase 1 (TrxR1) is currently recognized as a
      plausible anticancer drug target. Here we analyzed the effects of TrxR1 targeting
      in the human A549 lung carcinoma cell line, having a very high basal TrxR1
      expression. We determined the total cellular TrxR activity to be 271.4 +/- 39.5
      nmol min(-1) per milligram of total protein, which by far exceeded the total
      thioredoxin activity (39.2 +/- 3.5 nmol min(-1) per milligram of total protein).
      Knocking down TrxR1 by approx 90% using siRNA gave only a slight effect on cell
      growth, irrespective of concurrent glutathione depletion (> or = 98% decrease),
      and no increase in cell death or distorted cell cycle phase distributions. This
      apparent lack of phenotype could probably be explained by Trx functions being
      maintained by the remaining TrxR1 activity. TrxR1 knockdown nonetheless yielded
      drug-specific modulation of cytotoxic efficacy in response to various
      chemotherapeutic agents. No changes in response upon exposure to auranofin or
      juglone were seen after TrxR1 knockdown, whereas sensitivity to 1-chloro-2,4
      dinitrobenzene or menadione became markedly increased. In contrast, a virtually
      complete resistance to cisplatin using concentrations up to 20 microM appeared
      upon TrxR1 knockdown. The results suggest that high overexpression of TrxR has an
      impact not necessarily linked to Trx function that nonetheless modulates drug
      specific cytotoxic responses.

PMID- 19766716
TI  - Multiple, temporal-specific roles for HNF6 in pancreatic endocrine and ductal
      differentiation.
AB  - Within the developing pancreas Hepatic Nuclear Factor 6 (HNF6) directly activates
      the pro-endocrine transcription factor, Ngn3. HNF6 and Ngn3 are each essential
      for endocrine differentiation and HNF6 is also required for embryonic duct
      development. Most HNF6(-/-) animals die as neonates, making it difficult to study
      later aspects of HNF6 function. Here, we describe, using conditional gene
      inactivation, that HNF6 has specific functions at different developmental stages
      in different pancreatic lineages. Loss of HNF6 from Ngn3-expressing cells
      (HNF6(Delta endo)) resulted in fewer multipotent progenitor cells entering the
      endocrine lineage, but had no effect on beta cell terminal differentiation.
      Early, pancreas-wide HNF6 inactivation (HNF6(Delta panc)) resulted in endocrine
      and ductal defects similar to those described for HNF6 global inactivation.
      However, all HNF6(Delta panc) animals survived to adulthood. HNF6(Delta panc)
      pancreata displayed increased ductal cell proliferation and metaplasia, as well
      as characteristics of pancreatitis, including up-regulation of CTGF, MMP7, and
      p8/Nupr1. Pancreatitis was most likely caused by defects in ductal primary cilia.
      In addition, expression of Prox1, a known regulator of pancreas development, was
      decreased in HNF6(Delta panc) pancreata. These data confirm that HNF6 has both
      early and late functions in the developing pancreas and is essential for
      maintenance of Ngn3 expression and proper pancreatic duct morphology.

PMID- 19766717
TI  - The Drosophila Activin-like ligand Dawdle signals preferentially through one
      isoform of the Type-I receptor Baboon.
AB  - How TGF-beta-type ligands achieve signaling specificity during development is
      only partially understood. Here, we show that Dawdle, one of four Activin-type
      ligands in Drosophila, preferentially signals through Babo(c), one of three
      isoforms of the Activin Type-I receptor that are expressed during development. In
      cell culture, Dawdle signaling is active in the presence of the Type-II receptor
      Punt but not Wit, demonstrating that the Type-II receptor also contributes to the
      specificity of the signaling complex. During development, different larval
      tissues express unique combinations of these receptors, and ectopic expression of
      Babo(c) in a tissue where it is not normally expressed at high levels can make
      that tissue sensitive to Dawdle signaling. These results reveal a mechanism by
      which distinct cell types can discriminate between different Activin-type signals
      during development as a result of differential expression of Type-I receptor
      isoforms.

PMID- 19766718
TI  - Duchenne, Charcot and Babinski, three neurologists of La Salpetriere Hospital,
      and their contribution to concepts of the central organization of motor synergy.
AB  - Many currently accepted notions of motor control originate from a few seminal
      concepts developed in the latter half of the 19th century (see Bennett and
      Hacker, 2002). The goal of this review is to retrace some current ideas about
      motor control back to the thought of three French neurologists of Hospital of the
      Salpetriere hospital in Paris during the latter half of the 19th century and
      early 20th century (Fig. 1): Guillaume Duchenne de Boulogne (1806-1875), Jean
      Martin Charcot (1825-1893), and Joseph Babinski (1857-1932). A common theoretical
      and methodological thread unites these three men as Charcot was taught neurology
      by Duchenne, and Babinski was trained by Charcot. The influential concepts
      developed by these pioneering French neurologists have been neglected for nearly
      a century and only rediscovered recently. We intend to highlight how these astute
      clinicians used their meticulous clinical observations of patients to reveal
      novel and original perspectives of motor co-ordination. Between 1850 and 1930,
      all three men played a major role in developing and shaping the entire field of
      normal and pathological motor control in addition to making important
      contributions to three major scientific issues; the centralist view of muscle
      sense, the emerging concept of muscle synergy in voluntary movements and in
      locomotion and finally the specific role of the cerebellum in muscle synergy. The
      important contributions of these men will be considered in the context of other
      significant schools of neurology from other countries. Finally, the concept of
      cerebellar asynergy as proposed by Babinski anticipated the development of the
      internal models which much later were able to provide a theoretical basis for
      understanding the mechanism of learned motor co-ordination involving the
      cerebellum.

PMID- 19766719
TI  - Impaired wound healing in mice lacking the basement membrane protein nidogen 1.
AB  - Nidogens 1 and 2 are ubiquitous basement membrane (BM) components, whose
      interactions in particular with laminin, collagen IV and perlecan have been
      considered important for BM formation. Genetic deletion of either NID gene does
      not reveal BM alterations suggesting compensatory roles for nidogens 1 and 2.
      However, neurological deficits in nidogen 1 null mice, not seen in the absence of
      nidogen 2, also suggest isoform specific functions. To test this further, skin
      wound healing which requires BM reformation was studied in adult nidogen 1
      deficient mice. Although re-epithelialization was not altered, the newly formed
      epidermis showed marked hyperproliferation and a delay in differentiation at day
      10 post injury. Distinct to control wounds, there was also considerable alpha
      smooth muscle actin staining in the dermis of nidogen 1 deficient wounds at this
      time point. Further, laminin deposition and distribution of the beta1 and beta4
      integrin chains were also significantly altered whereas the deposition of other
      BM components, including nidogen 2, was unchanged. Surprisingly, these
      differences between control and mutant wounds at day 10 post wounding did not
      affect the ultrastructural appearance of the dermo-epidermal BM suggesting a non
      structural role for nidogen 1 in wound repair.

PMID- 19766720
TI  - A beauvericin hot spot in the genus Isaria.
AB  - Beauvericin is a naturally occurring cyclohexadepsipeptide originally described
      from Beauveria bassiana but also reported from several Fusarium species as well
      as members of the genus Isaria. Twenty-six isolates of Isaria species and its
      Cordyceps teleomorph, and ten taxonomically close strains including Beauveria,
      Nomuraea and Paecilomyces species were sequenced and tested for beauvericin
      production. Trees using ITS rDNA and beta-tubulin sequence data were constructed
      and used to infer the phylogenetic distribution of beauvericin production. A
      group comprising Isaria tenuipes and its known teleomorph Cordyceps takaomontana,
      Isaria cicadae and its Cordyceps teleomorph, Isaria japonica and Isaria
      fumosorosea, showed positive beauvericin production which correlated well with
      combined ITS rDNA and beta-tubulin phylogenies. The results suggested that
      beauvericin can serve as a chemotaxonomic marker for these limited species of the
      I. tenuipes complex.

PMID- 19766721
TI  - Antiapoptotic properties of recombinant human erythropoietin protects against
      tubular cyclosporine toxicity.
AB  - During the early post transplant period, the tubular epithelium is the main
      target of injuries including ischemia reperfusion and toxicity effects from
      calcineurin inhibitors. Taking into account the tissue protective effects of
      erythropoietin mediated through its antiapoptotic properties, we tested whether
      administration of recombinant human erythropoietin protects against acute
      cyclosporine nephrotoxicity. Four groups of five rats were intraperitoneally
      treated over 28 days with 100UI/Kg/48h Epoetin beta (15mg/kg/day CsA diluted in
      olive oil, 100UI/Kg/48h Epoetin beta+15mg/kg/day CsA, or olive oil. Histological
      changes due to tubular necrosis were evaluated with Masson'Trichrome staining.
      Apoptotic nuclei in kidneys were detected using the Terminal deoxynucleotidyl
      Transferase Biotin-dUTP Nick End Labeling (TUNEL) method. Phospho-Akt, Akt,
      cleaved caspase 3 and non cleaved caspase 3 expression were evaluated using
      immunblotting. We demonstrate that recombinant human erythropoietin (epoetin
      beta) improves renal function and protects against acute tubular injury. Our data
      suggest that this nephroprotective effect is mediated by Akt activation and
      inhibition of tubular apoptosis. Indeed, western blotting analysis of caspase 3
      cleavage and Akt phosphorylation demonstrates that rhEPO activate Akt signaling
      and inhibits caspase 3 cleavage induced by CsA. TUNEL staining confirms that
      rhEPO inhibits CsA-induced tubular apoptosis. In conclusion, we describe here a
      new potential target of recombinant human erythropoietin and our results provide
      an interesting framework for further nephroprotective therapies based on
      recombinant human erythropoietin.

PMID- 19766722
TI  - Purification, characterization, and crystallization of the adhesive domain of
      SdrD from Staphylococcus aureus.
AB  - The adhesive domain of SdrD from Staphylococcus aureus was solubly expressed in
      Escherichia coli in high yield. After a series of purification steps, the
      purified protein was >95% pure, which was SdrD from S. aureus identified by SDS
      PAGE and MALDI-TOF MS. Crystals were grown at 18 degrees C using 25% polyethylene
      glycol 3350 as precipitant. Diffraction by the crystal extends to 1.65A
      resolution, and the crystal belongs to the space group C2, with the unit cell
      parameters a=133.3, b=58.3, c=112.3A, alpha=90.00, beta=111.14, gamma=90.00.

PMID- 19766723
TI  - Expression, purification and characterization of UvrD2 helicase from
      Mycobacterium tuberculosis.
AB  - Helicases appear to be important for genome stability of dormant Mycobacterium
      tuberculosis responsible for latent tuberculosis infection and big proportion of
      active disease cases caused by reactivation. It was demonstrated that in both M.
      tuberculosis and Mycobacterium smegmatis, a helicase termed UvrD2 is essential
      for bacterial growth making it a promising target to fight tuberculosis. In many
      cases expression of soluble and active mycobacterial proteins in Escherichia coli
      is a complicated issue. In this work we for the first time report a non-trivial
      expression procedure in E. coli, leading to soluble UvrD2 from M. tuberculosis
      which possesses DNA-dependent ATP-ase activity.

PMID- 19766724
TI  - Soluble expression and purification of a crab antimicrobial peptide scygonadin in
      different expression plasmids and analysis of its antimicrobial activity.
AB  - Scygonadin is an anionic antimicrobial peptide recently identified from the
      seminal plasma of Scylla serrata. To gain more detailed information on its
      antimicrobial activity, scygonadin mature peptide was expressed in Escherichia
      coli in order to obtain a large quantity of biologically active product. An
      approximately 43 kDa fusion protein CKS-scygonadin was obtained in a highly
      stable and soluble form. The soluble component of the fusion CKS-scygonadin was
      purified by immobilized metal affinity chromatography (IMAC). A single 11 kDa
      recombinant scygonadin was cleaved from CKS-scygonadin and purified from the
      cleavage mixture using an affinity chromatography column with a yield of 10.6
      mg/L. Alternatively, a recombinant scygonadin was purified from pET28-scygonadin
      by one-step Ni(2+) affinity chromatography and 65.9 mg/L pure recombinant
      scygonadin was obtained which was higher than that purified from pTrc
      CKS/scygonadin in bacteria culture. The recombinant scygonadin was confirmed
      using SDS-PAGE analysis and MS-fingerprinting. Both recombinant products of
      scygonadin from different expressed plasmids showed the activity against both
      Gram-positive and Gram-negative bacteria, but no activity against yeast and fungi
      tested. The kinetic studies showed that the recombinant scygonadin was strong
      active against Staphylococcus aureus and the killing of S. aureus appeared time
      and dose dependent. Considering the quantity of recombinant product and the
      applicability of purification, the pET28-scygonadin expression system is a better
      choice to produce large quantities of recombinant scygonadin for commercial use
      in future. This is the first report on the heterologous expression of
      antimicrobial peptide scygonadin in E. coli.

PMID- 19766725
TI  - Chromocentre integrity and epigenetic marks.
AB  - The epigenetic modification of histones dictates the formation of euchromatin and
      heterochromatin domains. We studied the effects of a deficiency of histone
      methyltransferase, SUV39h, and trichostatin A-dependent hyperacetylation on the
      structural stability of centromeric clusters, called chromocentres. We did not
      observe the expected disintegration of chromocentres, but both SUV39h deficiency
      and hyperacetylation in SUV39h+/+ cells induced the re-positioning of
      chromocentres closer to the nuclear periphery. Conversely, TSA treatment of
      SUV39h-/- cells re-established normal nuclear radial positioning of
      chromocentres. This structural re-arrangement was likely caused by several
      epigenetic events at centromeric heterochromatin. In particular, reciprocal
      exchanges between H3K9me1, H3K9me2, H3K9me3, DNA methylation, and HP1 protein
      levels influenced chromocentre nuclear composition. For example, H3K9me1 likely
      substituted for the function of H3K9me3 in chromocentre nuclear arrangement and
      compaction. Our results illustrate the important and interchangeable roles of
      epigenetic marks for chromocentre integrity. Therefore, we propose a model for
      epigenetic regulation of nuclear stability of centromeric heterochromatin in the
      mouse genome.

PMID- 19766726
TI  - Molecular phylogenetics and historical biogeography of Rhinolophus bats.
AB  - The phylogenetic relationships within the horseshoe bats (genus Rhinolophus) are
      poorly resolved, particularly at deeper levels within the tree. We present a
      better-resolved phylogenetic hypothesis for 30 rhinolophid species based on
      parsimony and Bayesian analyses of the mitochondrial cytochrome b gene and three
      nuclear introns (TG, THY and PRKC1). Strong support was found for the existence
      of two geographic clades within the monophyletic Rhinolophidae: an African group
      and an Oriental assemblage. The relaxed Bayesian clock method indicated that the
      two rhinolophid clades diverged approximately 35 million years ago and results
      from Dispersal Vicariance (DIVA) analysis suggest that the horseshoe bats arose
      in Asia and subsequently dispersed into Europe and Africa.

PMID- 19766727
TI  - Memoirs of a locust: density-dependent behavioral change as a model for learning
      and memory.
AB  - A locust outbreak is a stupendous natural phenomenon that remains in the memory
      of whoever has been lucky (or unlucky) enough to witness it. Recent years have
      provided novel and important insights into the neurobiology of locust swarming.
      However, the central nervous system processes that accompany and perhaps even lie
      at the basis of locust phase transformation are still far from being fully
      understood. Our current work deals with the memory of a locust outbreak from a
      new perspective: that of the individual locust. We take locust density-dependent
      phase transformation - a unique example of extreme behavioral plasticity, and
      place it within the context of the accepted scheme of learning and memory. We
      confirm that a short time period of exposure to a small crowd of locusts is
      sufficient to induce a significant behavioral change in a previously solitary
      locust. Our results suggest that part of the behavioral change is due to long
      term habituation of evasive and escape responses. We further demonstrate that the
      memory of a crowding event lasts for at least 24h, and that this memory is
      sensitive to a protein synthesis blocker. These findings add much to our
      understanding of locust density-dependent phase polyphenism. Furthermore, they
      offer a novel and tractable model for the study of learning and memory-related
      processes in a very distinctive behavioral context.

PMID- 19766728
TI  - Contextual, but not auditory, fear conditioning is disrupted by neurotoxic
      selective lesion of the basal nucleus of amygdala in rats.
AB  - The basolateral amygdala complex (BLA) is involved in acquisition of contextual
      and auditory fear conditioning. However, the BLA is not a single structure but
      comprises a group of nuclei, including the lateral (LA), basal (BA) and accessory
      basal (AB) nuclei. While it is consensual that the LA is critical for auditory
      fear conditioning, there is controversy on the participation of the BA in fear
      conditioning. Hodological and neurophysiological findings suggest that each of
      these nuclei processes distinct information in parallel; the BA would deal with
      polymodal or contextual representations, and the LA would process unimodal or
      elemental representations. Thus, it seems plausible to hypothesize that the BA is
      required for contextual, but not auditory, fear conditioning. This hypothesis was
      evaluated in Wistar rats submitted to multiple-site ibotenate-induced damage
      restricted to the BA and then exposed to a concurrent contextual and auditory
      fear conditioning training followed by separated contextual and auditory
      conditioning testing. Differing from electrolytic lesion and lidocaine
      inactivation, this surgical approach does not disturb fibers of passage
      originating in other brain areas, restricting damage to the aimed nucleus.
      Relative to the sham-operated controls, rats with selective damage to the BA
      exhibited disruption of performance in the contextual, but not the auditory,
      component of the task. Thus, while the BA seems required for contextual fear
      conditioning, it is not critical for both an auditory-US association, nor for the
      expression of the freezing response.

PMID- 19766730
TI  - Iron overload in patients receiving allogeneic hematopoietic stem cell
      transplantation: quantification of iron burden by a superconducting quantum
      interference device (SQUID) and therapeutic effectiveness of phlebotomy.
AB  - Iron overload (IO) is a known adverse prognostic factor in patients who undergo
      allogeneic hematopoietic stem cell transplantation (HSCT) for thalassemia and
      appears to play a similar role in patients with other hematologic disorders. The
      estimation of IO is based primarily on serum ferritin level; however, many
      confounding factors can result in ferritin overestimation, especially in HSCT
      recipients. The aim of the present study was to quantify IO after HSCT using a
      superconducting quantum interference device (SQUID), and to evaluate the impact
      of IO on hepatic function and infections. In addition, the feasibility of iron
      depletion was investigated. A total of 102 consecutive allogeneic HSCT recipients
      admitted to our outpatient department between December 2005, and December 2007,
      were analyzed. Primary diagnosis included acute leukemia/myelodysplastic syndrome
      in 61% of cases. Assessment of IO after HSCT included serum ferritin; in those
      with hyperferritinemia (ferritin>1000 ng/mL), liver iron concentration (LIC) was
      evaluated by SQUID magnetic susceptometry. Iron removal therapy was offered to
      patients with moderate IO (LIC 1000-2000 microg Fe/g wet weight [ww]) or severe
      IO (LIC >2,000 microg Fe/g ww). Fifty-seven patients had a ferritin level <1000
      ng/mL: the median time between HSCT and assessment of ferritin level was 1006
      days (range, 93-5239 days), significantly different from the median time of 183
      days (range, 78-2957 days) in the 45 patients with a ferritin level >1000 ng/mL.
      Out of 42 patients evaluated by SQUID, 29 had moderate to severe IO (median LIC
      value, 1493 microg Fe/g ww [range, 1030-3253]). In a multivariate analysis, a
      significant correlation was found between a ferritin level >1000 ng/mL and the
      presence of at least one abnormal liver function test (LFT) ORo=6.8; 95% CI=2.2
      20.6). In addition, the rate of proven/probable invasive fungal disease was
      significantly higher in the patients with hyperferritinemia (13% vs 0%; P=.006).
      Nineteen of the 24 patients considered eligible for iron-depletion therapy
      underwent regular phlebotomy; 13 completed the program in a median of 287 days
      (range, 92-779 days), reaching the target of a ferritin level<500 ng/mL; LIC was
      significantly reduced (median, 1419 microg Fe/g ww to 625 microg Fe/g ww; P <
      .001) in 8 of the 9 patients who were revaluated by SQUID at the end of the iron
      depletion program. In conclusion, the measurement of LIC obtained by SQUID
      documented the presence of moderate/severe IO in 69% of the patients with a high
      ferritin level. Our data showed that in HSCT recipients, high ferritin level is
      an independent risk factor for abnormal LFTs, and IO may be considered a
      potential risk factor for fungal infections. A phlebotomy program may be feasible
      in two-thirds of the patients who might benefit from iron depletion.

PMID- 19766729
TI  - Hepatic veno-occlusive disease following stem cell transplantation: incidence,
      clinical course, and outcome.
AB  - The occurrence of hepatic veno-occlusive disease (VOD) has been reported in up to
      60% of patients following stem cell transplantation (SCT), with incidence varying
      widely between studies depending on the type of transplant, conditioning regimen,
      and criteria used to make the diagnosis. Severe VOD is characterized by high
      mortality and progression to multiorgan failure (MOF); however, there is no
      consensus on how to evaluate severity. This review and analysis of published
      reports attempts to clarify these issues by calculating the overall mean
      incidence of VOD and mortality from severe VOD, examining the effect of changes
      in SCT practice on the incidence of VOD over time, and discussing the methods
      used to evaluate severity. Across 135 studies performed between 1979 and October
      2007, the overall mean incidence of VOD was 13.7% (95% confidence interval
      [CI]=13.3%-14.1%). The mean incidence of VOD was significantly lower between 1979
      1994 than between 1994-2007 (11.5% [95% CI, 10.9%-12.1%] vs 14.6% [95% CI, 14.0%
      15.2%]; P <.05). The mortality rate from severe VOD was 84.3% (95% CI, 79.6%
      88.9%); most of these patients had MOF, which also was the most frequent cause of
      death. Thus, VOD is less common than early reports suggested, but the current
      incidence appears to be relatively stable despite recent advances in SCT,
      including the advent of reduced-intensity conditioning. The evolution of MOF in
      the setting of VOD after SCT can be considered a reliable indication of severity
      and a predictor of poor outcome.

PMID- 19766731
TI  - Purification and partial characterization of a midgut membrane-bound alpha
      glucosidase from Quesada gigas (Hemiptera: Cicadidae).
AB  - Adults of Quesada gigas (Hemiptera: Cicadidae) have a major alpha-glucosidase
      bound to the perimicrovillar membranes, which are lipoprotein membranes that
      surround the midgut cell microvilli in Hemiptera and Thysanoptera. Determination
      of the spatial distribution of alpha-glucosidases in Q. gigas midgut showed that
      this activity is not equally distributed between soluble and membrane-bound
      isoforms. The major membrane-bound enzyme was solubilized in the detergent Triton
      X-100 and purified to homogeneity by means of gel filtration on Sephacryl S-100,
      and ion-exchange on High Q and Mono Q columns. The purified alpha-glucosidase is
      a protein with a pH optimum of 6.0 against the synthetic substrate p-nitrophenyl
      alpha-D-glucoside and M(r) of 61,000 (SDS-PAGE). Taking into account V(Max)/K(M)
      ratios, the enzyme is more active on maltose than sucrose and prefers
      oligomaltodextrins up to maltopentaose, with lower efficiency for longer chain
      maltodextrins. The Q. gigas alpha-glucosidase was immunolocalized in
      perimicrovillar membranes by using a monospecific polyclonal antibody raised
      against the purified enzyme from Dysdercus peruvianus. The role of this enzyme in
      xylem fluid digestion and its possible involvement in osmoregulation is
      discussed.

PMID- 19766732
TI  - Evidence of an intact N-terminal translocation sequence of human mitochondrial
      adenylate kinase 4.
AB  - Adenylate kinases are abundant nucleoside monophosphate kinases, which catalyze
      the phosphorylation of AMP by using ATP or GTP as phosphate donors. A previously
      cloned cDNA was named adenylate kinase 4 (AK4) based on its sequence similarity
      with known AKs but with no confirmed AK enzyme activity. In the present study the
      AK4 cDNA was expressed in Escherichia coli and the substrate specificity and
      kinetic properties of the recombinant protein were characterized. The enzyme
      catalyzed the phosphorylation of AMP, dAMP, CMP and dCMP with ATP or GTP as
      phosphate donors and AK4 also phosphorylated AMP with UTP as phosphate donor. The
      kinetic parameters of the enzyme were determined for AMP and dAMP with ATP as
      phosphate donor and for AMP with GTP as phosphate donor. AK4 showed its highest
      efficiency when phosphorylating AMP with GTP and a slightly lower efficiency for
      the phosphorylation of AMP with ATP. Among the three reactions for which kinetics
      were performed, dAMP was the poorest substrate. The AK4 mitochondrial
      localization was confirmed by expression of AK4 as a fusion protein with GFP in
      HeLa cells. The mitochondrial import sequence was shown to be located within the
      first N-terminal 11 amino acid residues, very close to the ATP-binding region of
      the enzyme. Import analysis suggested that the mitochondrial import sequence was
      not cleaved and thus the enzyme retained its activity upon entering the
      mitochondria. Site directed mutagenesis of amino acids Lys 4 and Arg 7 showed
      that these two residues were essential for mitochondrial import.

PMID- 19766733
TI  - Spermatogenesis and sperm structure in Carpoglyphus lactis (L.) (Acari:
      Astigmata).
AB  - Testes, spermatogenesis and spermatozoa are described in the mite Carpoglyphus
      lactis (L.), the first representative of the Hemisarcoptoidea superfamily studied
      ultrastructurally. Paired testes are located posteriorly in the idiosoma, with
      germaria situated dorsolaterally. The germarium consists of a compact group of
      spermatogonia; no testicular central cell was found. The remainder of the gonad
      is occupied by germ cells in different stages of spermatogenesis, distributed
      separately rather than in cysts, and embedded in a few large somatic cells
      filling the remaining space. Spermatocytes are covered by a spongy layer, a
      product of the Golgi apparatus. Spermatids are anucleate. Their chromatin
      condenses into granular and then tubular threads. As spermiogenesis progresses,
      the spongy layer assembles at a single site and forms a structure termed the
      spongy body; mitochondria become electron dense, elongate and gather forming a
      bundle; a narrow ER cistern, promptly transforming into a dense lamella, appears
      between the mitochondria and chromatin. Mature spermatozoa are small, highly
      electron-dense cells interdigitating with others via superficial protrusions.
      They possess chromatin threads, electron-dense lamella and mitochondria, but do
      not have an acrosome. Our results support the monophyly of Astigmata, but do not
      explain the phylogenetic affinities of Hemisarcoptoidea to other superfamilies of
      astigmatic mites.

PMID- 19766735
TI  - Cloning of mouse ojoplano, a reticular cytoplasmic protein expressed during
      embryonic development.
AB  - Ojoplano (Opo) is a morphogenetic gene playing an important role during
      embryogenesis in medaka. This report focuses on the identification and
      characterization of the mouse Opo gene. We examined Opo expression by whole-mount
      in situ hybridization and in situ hybridization on sagittal sections during mouse
      embryogenesis. First expression in whole-mounts was detected at Theiler stages 15
      17 (E 9.5-10.5dpc) as a spotted specific staining in migrating neural crest cells
      and in placodal structures. A complex expression pattern was observed in Theiler
      stage 22-23 (E 14.5dpc) in sagittal sections, including expression in skeletal
      structures (skull, vertebrae, ribs, bones of the locomotor system), in the nasal
      region, the heart and the eye. Fusion proteins revealed the localization of OPO
      within the cytoplasm with a reticular distribution that largely overlapped with
      the endoplasmic reticulum. Opo shows homology to human transcripts linked to a
      hereditary craniofacial malformation, orofacial cleft 1 (OFC1). The expression of
      mouse Opo in neural crest derivatives and skull elements further supports this
      link.

PMID- 19766734
TI  - Trial design: The St. Jude Children's Research Hospital Cancer Survivors Tobacco
      Quit Line study.
AB  - Nearly, one-fifth of childhood cancer survivors (CCSs) smoke cigarettes. Because
      CCSs are already at greater medical smoking-related risks, targeting them for
      smoking cessation efforts is a high priority. One of the major challenges with
      smoking cessation in CCSs is how to reach such a geographically dispersed
      population. This study aims to demonstrate that these challenges can be overcome
      through the use of telephone-based tobacco quit lines (QLs). This report
      describes the design of the St. Jude Cancer Survivor Tobacco QL study, which is a
      randomized controlled clinical trial that will examine the long-term (1-year)
      efficacy of a counselor initiated vs. participant initiated tobacco QL with
      adjunctive nicotine replacement therapy (NRT) in both groups. Participants
      (N=950) will be recruited nationally and randomly assigned to one of the two
      interventions. The counselor initiated intervention includes six scheduled
      telephone sessions of a behavioral intervention and provision of 8 weeks of NRT.
      The participant initiated intervention allows the participant to call the QL at
      their convenience, but includes the same six telephone sessions and provision of
      2 weeks of NRT. Both groups will receive two follow-up phone calls at 8 weeks and
      1 year after enrollment to assess their smoking status. The primary outcome
      measure is cotinine-validated self-reported smoking abstinence at 1-year follow
      up. Results from this study will provide the first evidence about the efficacy of
      intensive QL cessation intervention in this high-risk population. Such evidence
      can lead as well to the dissemination of this intervention to other medically
      compromised populations.

PMID- 19766736
TI  - Structural and biochemical changes in mitochondria after cisplatin treatment of
      Dalton's lymphoma-bearing mice.
AB  - Cisplatin treatment of tumor-bearing mice and analysis of ultrastructural
      features of mitochondria in the kidney and Dalton's lymphoma cells showed the
      appearance of more roundish mitochondria with thickened membranes. It also caused
      the reduction in the number and irregularity in the shape of cristae and
      formation of vacuoles in the mitochondria. After cisplatin treatment, decreased
      level of protein, succinate dehydrogenase activity, and increased level of lipid
      peroxidation were noted in Dalton's lymphoma tumor cells and kidney. Cisplatin
      mediated decrease in SDH activity, GSH level and an increase in LPO in the
      mitochondria of kidney could play an important role to produce nephrotoxicity.
      However, in DL cells, decrease in cellular GSH could be noteworthy than mt-GSH,
      along with decrease in SDH activity and increase in LPO in the cisplatin-mediated
      anticancer activity. These changes could play an important role to produce both
      the cisplatin-mediated effects i.e. anticancer activity and nephrotoxicity.
      Cisplatin-induced biochemical and ultrastructural changes in mitochondria after
      cisplatin treatment should be an important factor in the development of
      biochemical injury in mitochondria and affecting the overall metabolism in the
      cells. The findings from the present studies indicate multilevel effect of
      cisplatin in the cells and do support the earlier view that mitochondria could be
      a critical target in cisplatin-mediated anticancer activity and toxicity in the
      hosts.

PMID- 19766738
TI  - Protein kinase and phosphatase signaling in Mycobacterium tuberculosis physiology
      and pathogenesis.
AB  - Mycobacterium tuberculosis (Mtb), the etiological agent of tuberculosis (TB),
      evades the antimicrobial defenses of the host and survives within the infected
      individual through a complex set of strategies. These include active prevention
      of host cellular killing processes as well as overwhelming adaptive gene
      expression. In the past decade, we have gained an increased understanding of how
      mycobacteria not only have the ability to adapt to a changing host environment
      but also actively interfere with the signaling machinery within the host cell to
      counteract or inhibit parts of the killing apparatus employed by the macrophage.
      Mtb is able to sense its environment via a set of phospho-signaling proteins
      which mediate its response and interaction with the host in a coordinated manner.
      In this review, we summarize the current knowledge about selected Mtb serine,
      threonine, and tyrosine kinase and phosphatase signaling proteins, focusing on
      the protein kinases, PknG and PtkA, and the protein phosphatase, PtpA.

PMID- 19766737
TI  - Structural basis for sirtuin function: what we know and what we don't.
AB  - The sirtuin (silent information regulator 2) proteins are NAD(+)-dependent
      deacetylases that are implicated in diverse biological processes including DNA
      regulation, metabolism, and longevity. Homologues of the prototypic yeast Sir2p
      have been identified in all three kingdoms of life, and while bacteria and
      archaea typically contain one to two sirtuins, eukaryotic organisms contain
      multiple members. Sirtuins are regulated in part by the cellular concentrations
      of the noncompetitive inhibitor, nicotinamide, and several synthetic modulators
      of these enzymes have been identified. The x-ray crystal structures of several
      sirtuin proteins in various liganded forms have been determined. This wealth of
      structural information, together with related biochemical studies, have provided
      important insights into the catalytic mechanism, substrate specificity, and
      inhibitory mechanism of sirtuin proteins. Implications for future structural
      studies to address outstanding questions in the field are also discussed.

PMID- 19766739
TI  - Photo-induced unfolding and inactivation of bovine carbonic anhydrase in the
      presence of a photoresponsive surfactant.
AB  - Photoreversible changes in the conformation and enzymatic activity of bovine
      carbonic anhydrase have been investigated as a function of photoresponsive
      surfactant concentration and light conditions. The light-responsive surfactant
      undergoes a photoisomerization from the relatively hydrophobic trans isomer under
      visible light to the relatively hydrophilic cis isomer upon UV illumination,
      providing a means to photoreversibly control enzyme-surfactant interactions.
      Small-angle neutron scattering and dynamic light scattering measurements, along
      with fluorescence spectroscopy, indicate that carbonic anhydrase unfolds upon
      addition of the surfactant under visible light, while only a small degree of
      unfolding is observed under UV light. Therefore, the enzyme is completely
      inactivated in the presence of the trans surfactant, while 40% of the native
      activity is preserved under UV light, providing a photoreversible "on/off switch"
      of enzyme activity. Small-angle neutron scattering data provide details of the in
      vitro conformational changes of the enzyme in response to the photosurfactant and
      light, with the enzyme found to aggregate as a result of photosurfactant-induced
      unfolding. Fourier transform infrared (FT-IR) spectroscopy further provides
      information on the secondary structure changes of the protein in the presence of
      photosurfactant.

PMID- 19766740
TI  - Structure-based discovery of small molecules targeting different surfaces of
      protein-kinase CK2.
AB  - Protein kinase CK2 is an unfavorable pronostic marker in several cancers and has
      consequently emerged as a relevant therapeutic target. Several classes of ATP
      competitive inhibitors have been identified, showing variable effectiveness. The
      molecular architecture of this multisubunit enzyme could offer alternative
      strategies to develop small molecule inhibitors targeting different surfaces of
      the kinase. Polyoxometalates were identified as original CK2 inhibitors targeting
      key structural elements located outside the active site. In addition, the CK2
      subunit interface represents an exosite distinct from the catalytic cavity that
      can be targeted by peptides or small molecules to achieve functional effects.

PMID- 19766741
TI  - Function and regulation of the mitochondrial sirtuin isoform Sirt5 in Mammalia.
AB  - Sirtuins are a family of protein deacetylases that catalyze the nicotinamide
      adenine dinucleotide (NAD(+))-dependent removal of acetyl groups from modified
      lysine side chains in various proteins. Sirtuins act as metabolic sensors and
      influence metabolic adaptation but also many other processes such as stress
      response mechanisms, gene expression, and organismal aging. Mammals have seven
      Sirtuin isoforms, three of them - Sirt3, Sirt4, and Sirt5 - located to
      mitochondria, our centers of energy metabolism and apoptosis initiation. In this
      review, we shortly introduce the mammalian Sirtuin family, with a focus on the
      mitochondrial isoforms. We then discuss in detail the current knowledge on the
      mitochondrial isoform Sirt5. Its physiological role in metabolic regulation has
      recently been confirmed, whereas an additional function in apoptosis regulation
      remains speculative. We will discuss the biochemical properties of Sirt5 and how
      they might contribute to its physiological function. Furthermore, we discuss the
      potential use of Sirt5 as a drug target, structural features of Sirt5 and of an
      Sirt5/inhibitor complex as well as their differences to other Sirtuins and the
      current status of modulating Sirt5 activity with pharmacological compounds.

PMID- 19766742
TI  - Comparison of two methods of fatigue testing bone cement.
AB  - Two different methods have been used to fatigue test four bone cements. Each
      method has been used previously, but the results have not been compared. The ISO
      527-based method tests a minimum of 10 samples over a single stress range in
      tension only and uses Weibull analysis to calculate the median number of cycles
      to failure and the Weibull modulus. The ASTM F2118 test regime uses fewer
      specimens at various stress levels tested in fully reversed tension-compression,
      and generates a stress vs. number of cycles to failure (S-N) or Wohler curve.
      Data from specimens with pores greater than 1mm across is rejected. The ISO 527
      based test while quicker to perform, provides only tensile fatigue data, but the
      material tested includes pores, thus the cement is closer to cement in clinical
      application. The ASTM regime uses tension and compression loading and multiple
      stress levels, thus is closer to physiological loading, but excludes specimens
      with defects obviously greater than 1mm, so is less representative of cement in
      vivo. The fatigue lives between the cements were up to a factor 15 different for
      the single stress level tension only tests, while they were only a factor of 2
      different in the fully reversed tension-compression testing. The ISO 527-based
      results are more sensitive to surface flaws, thus the differences found using
      ASTM F2118 are more indicative of differences in the fatigue lives. However, ISO
      527-based tests are quicker, so are useful for initial screening.

PMID- 19766743
TI  - Interaction of an ordered mesoporous bioactive glass with osteoblasts,
      fibroblasts and lymphocytes, demonstrating its biocompatibility as a potential
      bone graft material.
AB  - Ordered mesoporous 85SiO(2)-10CaO-5P(2)O(5) bioactive glass (MBG85) is an
      excellent candidate as a graft for bone tissue regeneration, owing to its
      excellent textured properties, structural characteristics and crystalline apatite
      rate formation. To assess MBG85 biocompatibility, different parameters have been
      evaluated (cell morphology, size/complexity, proliferation, viability, cell
      cycle, reactive oxygen species content, lactate dehydrogenase release) using
      human Saos-2 osteoblasts after treatment with either MBG85 extracts or 1% MBG85
      directly added to cells. The osteoblast response to MBG85 was compared with L929
      fibroblast behaviour after the same treatment. The high cell viability observed
      and the absence of signs of cell damage in both cell types demonstrates MBG85
      biocompatibility. Only a cytostatic effect was observed through the reduction of
      cell proliferation, related with the initial Ca elution, whereas Si leaching did
      not result into any negative effect. In vitro lymphocytic proliferation analysis
      was also carried out with SR.D10 clone after treatment with either MBG85 extracts
      or culture supernatants of L929 fibroblasts previously treated with 1% MBG85
      (cell-conditioned extracts). The absence of modification of in vitro T-cell
      response underlines the biocompatibility of MBG85 and its potential application
      in the field of bone and dental grafting.

PMID- 19766744
TI  - Transplantation of human mesenchymal stem cells in a non-autogenous setting for
      bone regeneration in a rabbit critical-size defect model.
AB  - Human mesenchymal stem cells (hMSC) represent an attractive cell population for
      tissue engineering purposes. Furthermore, hMSC are described as immune
      privileged, and non-autogenous application seems possible. The current study
      examines the regeneration potential of hMSC after xenogenic transplantation
      compared with autogenous rabbit MSC in a critical-size bone defect. After
      isolation, hMSC and rabbit MSC were seeded on calcium-deficient hydroxyapatite
      (CDHA) and transplanted into a radial critical-size defect of New Zealand white
      rabbits. Defects were filled with a CDHA scaffold seeded with autogenous rabbit
      MSC, CDHA seeded with xenogenic hMSC or unseeded CDHA. An empty defect served as
      control group. Animals were sacrificed after 3 months. Evaluation was performed
      using radiography, micro-computed tomography (micro-CT) and histology. In
      addition, a non-destructive four-point-bending test was performed in order to
      evaluate biomechanical stiffness. While autogenous MSC seeded on CDHA led to
      increased healing of critical-size bone defects from radiological (micro-CT; p =
      0.009) and histological (p = 0.048) perspectives compared with unloaded CDHA, it
      was not possible to demonstrate analogous effects for the xenogenic
      transplantation of hMSC. The xenogenic treatment group displayed inferior results
      in all parameters compared with the autogenous MSC treatment group (histology p =
      0.041; micro-CT p = 0.006; biomechanical testing p = 0.017). Nevertheless, no
      local or systemic inflammatory response resulting from xenogenic transplantation
      was observed. While previous papers suggest the use of non-autogenous hMSC cells
      for tissue engineering purposes, the present results show inferior clinical
      results from transplantation of hMSC in a xenogenic setting compared with
      autogenous MSC.

PMID- 19766745
TI  - Pre-analytical operating procedures for serum Low Molecular Weight protein
      profiling.
AB  - Biological specimen collection and storage are an integral component of serum
      proteomics research. Although many efforts have been posed to address the effects
      of pre-analytical procedures, standardized protocols for collection and storage
      of samples for Low Molecular Weight (LMW) proteome profiling are still needed.
      Here we report a systematic analysis on the influence of pre-analytical factors
      [clotting times, temperature and time storage, addition of protease inhibitor
      (PI)] on serum LMW proteome profiling. Moreover, a comparison between manual
      versus automated peptide purification by functionalized magnetic bead-based MALDI
      MS approach was performed. The results demonstrated best serum LMW proteins
      recovery and stability using a clotting time between 1 and 2h, with serum stored
      up to 2h either at room temperature or at 4 degrees C, independently of PI
      addition. PI addition to whole blood resulted in a lower number of LMW peaks
      detected. Finally, minimal effects on serum proteome profiles were observed after
      1-month storage at -80 degrees C, independently of PI addition on whole blood
      and/or serum. In conclusion, the use of standardized pre-analytical and storage
      procedures together with an automated peptide purification might minimize
      potential bias on serum LMW profiling results, thus allowing a better homogeneity
      and reproducibility in future proteomics studies.

PMID- 19766746
TI  - A phenotypically restricted set of primary afferent nerve fibers innervate the
      bone versus skin: therapeutic opportunity for treating skeletal pain.
AB  - Although musculoskeletal pain is one of the most common causes of chronic pain
      and physical disability in both developing and developed countries, relatively
      little is known about the nerve fibers and mechanisms that drive skeletal pain.
      Small diameter sensory nerve fibers, most of which are C-fiber nociceptors, can
      be separated into two broad populations: the peptide-rich and peptide-poor nerve
      fibers. Peptide-rich nerve fibers express substance P (SP) and calcitonin gene
      related peptide (CGRP). In contrast, the peptide-poor nerve fibers bind to
      isolectin B4 (IB(4)) and express the purinergic receptor P(2)X(3) and Mas-related
      G protein-coupled receptor member d (Mrgprd). In the present report, we used mice
      in which the Mrgprd(+) nerve fibers express genetically encoded axonal tracers to
      determine the peptide-rich and peptide-poor sensory nerve fibers that innervate
      the glabrous skin of the hindpaw as compared to the bone marrow, mineralized bone
      and periosteum of the femur. Whereas the skin is richly innervated by CGRP(+),
      SP(+), P(2)X(3)(+) and Mrgprd(+) sensory nerve fibers, the bone marrow,
      mineralized bone and periosteum receive a significant innervation by SP(+) and
      CGRP(+), but not Mrgprd(+) and P(2)X(3)(+) nerve fibers. This lack of redundancy
      in the populations of C-fibers that innervate the bone may present a unique
      therapeutic opportunity for targeting skeletal pain as the peptide-rich and
      peptide-poor sensory nerve fibers generally express a different repertoire of
      receptors and channels to detect noxious stimuli. Thus, therapies that target the
      specific types of C-nerve fibers that innervate the bone may be uniquely
      effective in attenuating skeletal pain as compared to skin pain.

PMID- 19766747
TI  - Sex-specific effect of Pirin gene on bone mineral density in a cohort of 4000
      Chinese.
AB  - BACKGROUND: Osteoporosis is a common condition among elderly. Genetic mapping
      studies repeatedly located the distal short arms of X-chromosome as the
      quantitative trait loci (QTL) for BMD in mice. Fine mapping of a syntenic segment
      on Xp22 in a Caucasian female population suggested a moderate association between
      lumbar spine (LS) BMD and 2 intronic SNPs in the Pirin (PIR) gene, which encodes
      an iron-binding nuclear protein. This study aimed to examine genetic variations
      in the PIR gene by a comprehensive tagging method and its sex-specific effects on
      BMD and osteoporotic risk. METHODS: Two thousand men and 2000 women aged 65 or
      above were recruited from the community. BMDs at the LS, femoral neck, total hip
      and whole body were measured and followed up at 4-year. Genotyping was performed
      for tagSNPs of PIR gene including adjacent regions, and the PIR haplotypes were
      inferred using PHASE program. RESULTS: Analysis by linear regression showed a
      significant association between SNP rs5935970 and LS-BMD, while haplotype T-T-A
      was significantly associated with BMD of all measured sites. However, none of
      such associations were found in men. Linear Mixed Model also confirmed the same
      sex-specific and site-specific effect for longitudinal BMD changes. CONCLUSION:
      In addition to confirming the association between BMDs and the PIR gene, we also
      revealed that this finding is sex-specific, possibly due to an X-linked effect.
      This study demonstrated the importance of considering sex and genetic
      interactions in studies of disease predisposition and complex traits.

PMID- 19766748
TI  - Nmp4/CIZ: road block at the intersection of PTH and load.
AB  - Teriparatide (parathyroid hormone, [PTH]) is the only FDA-approved drug that
      replaces bone lost to osteoporosis. Enhancing PTH efficacy will improve cost
      effectiveness and ameliorate contraindications. Combining this hormone with load
      bearing exercise may enhance therapeutic potential consistent with a growing body
      of evidence that these agonists are synergistic and share common signaling
      pathways. Additionally, neutralizing molecules that naturally suppress the
      anabolic response to PTH may also improve the efficacy of treatment with this
      hormone. Nmp4/CIZ (nuclear matrix protein 4/cas interacting zinc finger)-null
      mice have enhanced responses to intermittent PTH with respect to increasing
      trabecular bone mass and are also immune to disuse-induced bone loss likely by
      the removal of Nmp4/CIZ suppressive action on osteoblast function. Nmp4/CIZ
      activity may be sensitive to changes in the mechanical environment of the bone
      cell brought about by hormone- or mechanical load-induced changes in cell shape
      and adhesion. Nmp4 was identified in a screen for PTH-responsive nuclear matrix
      architectural transcription factors (ATFs) that we proposed translate hormone
      induced changes in cell shape and adhesion into changes in target gene DNA
      conformation. CIZ was independently identified as a nucleocytoplasmic shuttling
      transcription factor associating with the mechano-sensitive focal adhesion
      proteins p130Cas and zxyin. The p130Cas/zyxin/Nmp4/CIZ pathway resembles the beta
      catenin/TCF/LEF1 mechanotransduction response limb and both share features with
      the HMGB1 (high mobility group box 1)/RAGE (receptor for advanced glycation end
      products) signaling axis. Here we describe Nmp4/CIZ within the context of the PTH
      induced anabolic response and consider the place of this molecule in the
      hierarchy of the PTH-load response network.

PMID- 19766749
TI  - Impact of coronary computed tomographic angiography findings on the medical
      treatment and control of coronary artery disease and its risk factors.
AB  - Although coronary computed tomographic angiography (CCTA) has high diagnostic
      accuracy and increasing evidence of prognostic value for coronary artery disease
      (CAD), its downstream clinical impact is not established. In this study, the
      association of findings on CCTA with subsequent treatment and control of CAD risk
      factors was assessed in 208 consecutive symptomatic outpatients without known CAD
      who underwent CCTA. Blood pressure (BP), lipid levels, and CAD medications were
      compared before and after CCTA (mean follow-up period 8.1 +/- 6.6 months). CAD
      severity on CCTA was graded as absent, mild (1% to 49%), moderate (50% to 69%),
      or severe (> or =70%) stenosis. In patients with absent, mild, moderate, and
      severe CAD on CCTA, aspirin was initiated in 0%, 14%, 36%, and 15%; statins were
      initiated or increased in 4%, 23%, 44%, and 42% of patients; and BP medications
      were initiated or increased in 16%, 10%, 26%, and 38% of patients (p <0.05 for
      severe vs no CAD for all). Higher grades of CAD severity were independently
      associated with greater post-CCTA use of aspirin (odds ratio 3.2 per grade, p
      <0.001) and statins (odds ratio 3.6 per grade, p <0.001), but not BP medications.
      Greater CAD severity was independently associated with lower post-test total
      cholesterol (-8.2 mg/dl per grade, p = 0.02), low-density lipoprotein cholesterol
      (-6.8 mg/dl per grade, p = 0.04), and diastolic BP (-1.4 mm Hg per grade, p =
      0.03), but not systolic BP. In conclusion, greater CAD severity on CCTA is
      associated with enhanced medical treatment and improved control of CAD risk
      factors.

PMID- 19766750
TI  - Relation of plasma brain natriuretic peptide levels on admission for ST-elevation
      myocardial infarction to left ventricular end-diastolic volume six months later
      measured by both echocardiography and cardiac magnetic resonance.
AB  - The main objective of this study was to investigate the relation between brain
      natriuretic peptide (BNP) levels within the first 96 hours after ST-segment
      elevation acute myocardial infarction (STEMI) and the development of left
      ventricular (LV) dilatation at 6-month follow-up. Eighty-two patients with first
      STEMIs, reperfused within 12 hours of symptom onset, were prospectively included.
      Plasma BNP was determined on admission and at 1- and 6-month follow-up.
      Clinically significant LV dilatation, defined as a >20% increase in LV end
      diastolic volume at 6-month follow-up, was assessed using echocardiography and
      cardiac magnetic resonance. Thirty-two percent of patients developed clinically
      significant LV dilatation. BNP values on admission and at follow-up were
      significantly higher in patients who developed clinically significant LV
      dilatation at 6 months (182 +/- 117 vs 106 +/- 91 pmol/ml). After adjusting for
      age, infarct size, E-wave deceleration time, and the LV ejection fraction, BNP on
      admission was an independent predictor of LV dilatation, whether assessed by
      echocardiography (B = 0.075, p = 0.04) or cardiac magnetic resonance (B = 0.085,
      p = 0.04). In conclusion, high BNP levels on admission and at follow-up predict
      LV dilatation after STEMI. The early determination of plasma BNP upon admission
      for STEMI could be helpful in identifying patients at higher risk for LV
      dilatation, in whom aggressive management is warranted.

PMID- 19766751
TI  - Relation of obesity to heart failure hospitalization and cardiovascular events in
      persons with stable coronary heart disease (from the Heart and Soul Study).
AB  - Obesity is an independent risk factor for recurrent events among patients with
      established coronary heart disease (CHD). The goal of the present study was to
      identify potential mechanisms underlying this association. We measured the waist
      to-hip ratio and body mass index in 979 outpatients with stable CHD and followed
      them for a mean of 4.9 years. We used proportional hazards models to evaluate the
      extent to which the association of obesity with subsequent heart failure (HF)
      hospitalization or cardiovascular (CV) events (myocardial infarction, stroke, or
      CHD death) was explained by baseline co-morbidities, cardiac disease severity,
      inflammation, insulin resistance, neurohormones and adipokines. Of the 979
      participants, 128 (13%) were hospitalized for HF and 152 (16%) developed a CV
      event. Each standard deviation (SD) increase in the waist-to-hip ratio was
      associated with a 30% increased risk of HF hospitalization (unadjusted hazard
      ratio [HR] 1.3, 95% confidence interval [CI] 1.1 to 1.6). This association was
      not attenuated after adjustment for potential mediators (HR 1.6, 95% CI 1.2 to
      2.1). Likewise, each SD increase in the waist-to-hip ratio was associated with a
      20% greater risk of CV events (unadjusted HR 1.2, 95% CI 1.0 to 1.4), and this
      remained unchanged after adjustment for potential mediators (adjusted HR 1.3, 95%
      CI 1.0 to 1.5). The body mass index was not associated with the risk of HF or CV
      events. In conclusion, abdominal obesity is an independent predictor of HF
      hospitalization and recurrent CV events in patients with stable CHD. This
      association does not appear to be mediated by co-morbid conditions, cardiac
      disease severity, insulin resistance, inflammation, neurohormones, or adipokines.

PMID- 19766752
TI  - Assessment of subclinical coronary atherosclerosis in asymptomatic patients with
      type 2 diabetes mellitus with single photon emission computed tomography and
      coronary computed tomography angiography.
AB  - We evaluated the characteristics of coronary artery disease in asymptomatic
      patients with type 2 diabetes mellitus (DM) using single photon emission computed
      tomography (SPECT) and coronary computed tomographic angiography (CCTA). A total
      of 116 patients with DM without abnormal electrocardiographic findings or
      evidence of peripheral arterial disease (number of risk factors > or =2; 62 +/- 7
      years, 59% men) underwent CCTA and SPECT. Of the 116 patients with DM, 88 (76%)
      had a normal single photon emission computed tomographic findings, and 28 (24%)
      had abnormal perfusion defects. Of the 116 patients, 92 (79%) had atherosclerotic
      plaques (2 +/- 2 segments per subject), and 20 (17%) had significant stenosis
      seen on CCTA. Patients with DM and normal findings on SPECT had a similar
      prevalence of atherosclerotic plaque (78% vs 82%), significant stenosis (15% vs
      25%), severe stenosis (7% vs 7%), and calcified (40% vs 43%), mixed (49% vs 57%),
      and noncalcified plaques (26% vs 29%) and a high (>100) coronary artery calcium
      score (32% vs 29%; all p >0.05) compared to those with abnormal findings on
      SPECT. During the mid-term follow-up (24 +/- 4 months), 5 cardiac events occurred
      in patients with DM and normal findings on SPECT, only in those with occult CAD
      on CCTA: 1 sudden cardiac death and 4 revascularization procedures. In
      conclusion, a significant percentage of patients with DM and normal
      eletrocardiographic findings, no peripheral arterial disease, and normal findings
      on SPECT have evidence of occult CAD on CCTA. Furthermore, a small percentage had
      had a cardiac event by mid-term follow-up. SPECT showed limited capability to
      differentiate the coronary risks between patients with DM and no coronary plaque
      and from those with a certain degree of disease; 2 circumstances that represent
      different coronary risks.

PMID- 19766753
TI  - Interaction of left ventricular geometry and myocardial ischemia in the response
      of myocardial deformation to stress.
AB  - Myocardial deformation parameters are sensitive markers of global left
      ventricular (LV) systolic function, but their interaction with LV geometry is
      unknown. We sought to investigate the effect of LV geometry on myocardial
      deformation and its interaction with coronary artery disease (CAD). A total of
      126 patients with normal resting LV function who underwent dobutamine stress
      echocardiography subsequently underwent coronary angiography within 6 months.
      Longitudinal myocardial deformation was calculated using tissue Doppler
      echocardiography. The extent of CAD was identified by quantitative coronary
      angiography. Patients with an increased relative wall thickness had a
      significantly lower peak strain rate (SR) and a smaller change in SR with stress,
      with no differences in the at rest values. Those with CAD, had significantly
      lower peak SR values and change in SR with no difference in resting measures. A
      linear regression model showed that the relative wall thickness and extent of CAD
      were the strongest predictors of change in SR. An increasing extent of CAD caused
      a steady degradation in the peak SR and change in peak SR. Markers of
      longitudinal myocardial deformation at peak stress reflect both myocardial and
      interstitial properties. In conclusion, a major determinant of subendocardial
      function is the wall thickness, as measured by the relative wall thickness, and
      not LV hypertrophy.

PMID- 19766754
TI  - Relation of high concentrations of plasma carboxy-terminal telopeptide of
      collagen type I with outcome in acute myocardial infarction.
AB  - Acute myocardial infarction (AMI) is associated with matrix metalloproteinase
      activation. The plasma concentrations of carboxy-terminal telopeptide of collagen
      type I (CITP) reflect collagen type I degradation due to matrix metalloproteinase
      activation. We assessed the role of CITP as an early marker of outcome in AMI.
      Plasma CITP was measured 72 hours after hospital admission in 432 patients
      presenting with AMI. The 2 composite end points of the study (death, resuscitated
      cardiac arrest, recurrent AMI or ischemia, and heart failure or stroke; and
      death, resuscitated cardiac arrest, or heart failure) and mortality were assessed
      at 1 year in 4 patient groups stratified by the CITP quartiles. Patients with ST
      segment elevation MI represented 75.7% of the population. In-hospital
      percutaneous coronary intervention was performed in 70.4% of the patients. The
      mean left ventricular ejection fraction was 53.9 +/- 12.5%. At 1 year of follow
      up, high levels of CITP were associated with the occurrence of both composite end
      points and mortality (p <0.01 for all). Stepwise logistic regression analysis
      identified CITP as an independent predictor of both composite end points (odds
      ratio 2.14, 95% confidence interval 1.34 to 3.42, p = 0.001; and odds ratio 3.19,
      95% confidence interval 1.50 to 6.81, p = 0.003), along with the Killip class and
      brain natriuretic peptide levels. In conclusion, high hospital levels of CITP, a
      marker of collagen degradation and ventricular remodeling, are associated with
      late mortality and other serious clinical events after AMI.

PMID- 19766755
TI  - Comparison of incidence of acute myocardial infarction in patients with type 2
      diabetes mellitus following initiation of neutral protamine Hagedorn insulin
      versus insulin glargine.
AB  - Recent reports have described different risks of acute myocardial infarction
      (AMI) in association with specific oral antidiabetic medications. The present
      study compared the AMI incidence rates in new users of traditional neutral
      protamine Hagedorn (NPH) insulin and a long-acting synthetic insulin analog for
      basal insulin therapy. We retrospectively examined in-patient medical claims for
      AMI in a cohort of oral agent-treated patients with type 2 diabetes mellitus
      after the initiation of basal insulin therapy with either NPH (n = 5,461) or
      insulin glargine (n = 14,730) in a national administrative claims database
      comprising >30 managed healthcare plans in the United States. Poisson regression
      and Cox proportional hazards regression models, as well as the propensity score
      methods, were used to compare the subsequent AMI incidence rates after the
      initiation of NPH or glargine. At a mean follow-up of 2 years, the unadjusted AMI
      incidence was 17.6/1,000 person-years after the initiation of NPH versus
      11.5/1,000 person-years after initiation of glargine (rate ratio 1.53, 95%
      confidence interval 1.29 to 1.81). The Cox regression model (hazard ratio 1.39,
      95% confidence interval 1.14 to 1.69) and sensitivity analyses (hazard ratio
      range 1.30 to 1.56) showed a greater risk of AMI in the NPH group than in the
      glargine group. Propensity matched (1:1) analysis yielded similar results (odds
      ratio 1.55, 95% confidence interval 1.23 to 1.96 for NPH vs glargine). In
      conclusion, these results suggest that the initiation of basal insulin therapy
      with NPH rather than glargine in patients with type 2 diabetes mellitus is
      associated with a greater risk of AMI.

PMID- 19766756
TI  - Association of neutrophil gelatinase-associated lipocalin with the severity of
      coronary artery disease.
AB  - Serum neutrophil gelatinase-associated lipocalin (NGAL) concentrations were
      measured in 73 consecutive patients who underwent first-time angiography for
      suspected coronary artery disease (CAD), and their associations with angiographic
      indexes of the severity of CAD (i.e., number of diseased vessels and modified
      Gensini score) were estimated. Median serum NGAL levels in patients with
      angiographically confirmed CAD were significantly higher than those in patients
      with normal coronary arteries (29.0 ng/ml [interquartile range 25.2 to 36.8] vs
      22.4 ng/ml [interquartile range 17.34 to 32.0], p = 0.004). Statistically
      significant correlations were observed between serum NGAL level and the number of
      diseased vessels (r(s) = 0.390, p = 0.01) and modified Gensini score (r(s) =
      0.356, p = 0.002). Using multivariate analysis, serum NGAL level was
      independently associated with the presence and severity of CAD. In conclusion,
      serum NGAL levels are significantly higher in the presence of CAD and are
      correlated with the severity of the disease. Further clinical studies are needed
      to confirm the use of NGAL as a biomarker for the detection and extent of CAD.

PMID- 19766757
TI  - Efficacy of single-bolus administration of sodium bicarbonate to prevent contrast
      induced nephropathy in patients with mild renal insufficiency undergoing an
      elective coronary procedure.
AB  - We sought to clarify whether a single-bolus intravenous administration of sodium
      bicarbonate in addition to hydration with sodium chloride prevents contrast
      induced nephropathy (CIN). One hundred forty-four patients with mild renal
      insufficiency (serum creatinine >1.1 to <2.0 mg/dl) undergoing an elective
      coronary procedure were randomly assigned to the following 2 groups: standard
      hydration with sodium chloride plus single-bolus intravenous administration of
      sodium bicarbonate (20 mEq) immediately before contrast exposure (group A, n =
      72) and standard hydration alone (group B, n = 72). The primary end point was
      development of CIN, defined as an increase >25% or >0.5 mg/dl in serum creatinine
      within 3 days after the procedure. Incidence of the primary end point was lower
      in group A than in group B (1.4% vs 12.5%, p = 0.017). Incidence of adverse
      clinical events (acute pulmonary edema, acute renal failure requiring dialysis,
      and death within 7 days of procedure) did not differ between the 2 groups (0% vs
      1.4%). In conclusion, single-bolus intravenous administration of sodium
      bicarbonate in addition to standard hydration can more effectively prevent CIN
      than standard hydration alone in patients with mild renal insufficiency
      undergoing an elective coronary procedure.

PMID- 19766758
TI  - Comparison of effects of primary coronary angioplasty on left ventricular
      remodeling and heart failure in patients <70 versus > or =70 years with acute
      myocardial infarction.
AB  - Experimental studies have demonstrated the adverse effects of senescence on
      cardiac function and remodeling after acute myocardial infarction (AMI). We
      sought to assess the impact of age on left ventricular (LV) remodeling and heart
      failure (HF) after successful primary angioplasty for AMI. A series of 512
      consecutive patients underwent 2-dimensional echocardiography at admission and at
      1 month and 6 months after index AMI. LV volumes, ejection fraction, and wall
      motion score index (WMSI) were measured. Patients were divided in group 1 (<70
      years old, n = 361) and group 2 (> or =70 years old, n = 151). Group 2 patients
      showed a lower peak creatine kinase (p = 0.029) compared to group 1. In group 2
      patients the 6-month prevalence of LV remodeling (increase >20% in end-diastolic
      volume) was higher (34% vs 25%, p = 0.041), recoveries of ejection fraction and
      WMSI were lower (p = 0.00002 for the 2 comparisons), and incidence of late HF was
      higher (35% vs 17%, p <0.0001) compared to group 1 patients. Independent
      predictors of LV remodeling were WMSI (p <0.0001), infarct size (p <0.0001), and
      LV end-diastolic volume (p <0.0001). Independent predictors of late HF were WMSI
      (hazard ratio [HR] 2.7, 95% confidence interval [CI] 1.624 to 4.514), 6-month LV
      dilation (HR 2.13, 95% CI 1.404 to 3.233), diabetes (HR 1.6, 95% CI 1.008 to
      2.595), infarct size (HR 1.12, 95% CI 1.037 to 1.215), and age as continuous
      variables (HR 1.064, 95% CI 1.044 to 1.085). In conclusion, besides infarct size,
      extensive regional systolic dysfunction may play a significant role in the
      development of LV remodeling and HF in patients > or =70 years old after
      successful primary angioplasty.

PMID- 19766759
TI  - Relation of alcohol consumption and coronary heart disease in hypertensive male
      physicians (from the Physicians' Health Study).
AB  - Alcohol has diverse effects on the cardiovascular system. Moderate drinking is
      associated with a decreased risk of cardiovascular disease, yet increasing
      amounts of alcohol consumption are known to increase blood pressure. These
      opposing effects have led to interest in the effect of moderate alcohol
      consumption on the risk of coronary heart disease (CHD) in patients with
      hypertension. To test the hypothesis that moderate alcohol consumption decreases
      the risk of myocardial infarction (MI) in patients with hypertension, we used
      data on 5,164 participants in the Physicians' Health Study who were apparently
      healthy and free of CHD at baseline. Incident MI was ascertained by annual follow
      up questionnaires and validated through review of medical records. Cox
      proportional hazard model was used to compute multivariable-adjusted hazard
      ratios with corresponding 95% confidence intervals. From 1982 to 2008, 623 cases
      of MI occurred. Compared to subjects consuming <1 drink per week, hazard ratios
      for MI were 1.05 (95% confidence interval 0.85 to 1.28), 0.78 (95% confidence
      interval 0.64 to 0.97), and 0.57 (95% confidence interval 0.35 to 0.95) for
      alcohol consumption of 1 to 4, 5 to 7, and >8 drinks per week adjusted for age,
      body mass index, smoking, exercise, diabetes, multivitamin use, vegetable intake,
      breakfast cereal intake, and cholesterol (p for trend <0.0022). Similar
      inferences could be made for the secondary outcomes of angina pectoris and any
      CHD (which included MI, angina pectoris, and previous revascularization). In
      conclusion, our data demonstrated an inverse relation between moderate alcohol
      consumption and CHD in hypertensive men.

PMID- 19766760
TI  - Effects of consumption of pomegranate juice on carotid intima-media thickness in
      men and women at moderate risk for coronary heart disease.
AB  - This randomized, double-blind, parallel trial assessed the influence of
      pomegranate juice consumption on anterior and posterior carotid intima-media
      thickness (CIMT) progression rates in subjects at moderate risk for coronary
      heart disease. Subjects were men (45 to 74 years old) and women (55 to 74 years
      old) with > or =1 major coronary heart disease risk factor and baseline posterior
      wall CIMT 0.7 to 2.0 mm, without significant stenosis. Participants consumed 240
      ml/day of pomegranate juice (n = 146) or a control beverage (n = 143) for up to
      18 months. No significant difference in overall CIMT progression rate was
      observed between pomegranate juice and control treatments. In exploratory
      analyses, in subjects in the most adverse tertiles for baseline serum lipid
      peroxides, triglycerides (TGs), high-density lipoprotein (HDL) cholesterol,
      TGs/HDL cholesterol, total cholesterol/HDL cholesterol, and apolipoprotein-B100,
      those in the pomegranate juice group had significantly less anterior wall and/or
      composite CIMT progression versus control subjects. In conclusion, these results
      suggest that in subjects at moderate coronary heart disease risk, pomegranate
      juice consumption had no significant effect on overall CIMT progression rate but
      may have slowed CIMT progression in subjects with increased oxidative stress and
      disturbances in the TG-rich lipoprotein/HDL axis.

PMID- 19766761
TI  - Comparative relation of general, central, and visceral adiposity measures for
      coronary artery calcium in subjects without previous coronary events.
AB  - It is unclear whether visceral obesity is largely responsible for an increased
      risk of coronary artery disease. In the present study, 1,054 men underwent
      coronary artery calcium (CAC) scoring and abdominal computed tomography. Risk
      factor information, body mass index, waist circumference, and waist-to-hip ratio
      were collected for all participants. The total fat, visceral fat, and
      subcutaneous fat areas were also quantified at the level of the umbilicus using
      computed tomography. We then investigated the association of these obesity
      parameters with the CAC score. Participants with a CAC score >10 had a larger
      waist circumference (97 +/- 12 vs 95 +/- 12 cm, p <0.001), a larger total fat
      area (434 cm(2), interquartile range 339 to 565, vs 415 cm(2), interquartile
      range 315 to 521; p = 0.005), a larger visceral fat area (200 cm(2),
      interquartile range 143 to 256, vs 175 cm(2), interquartile range 124 to 225; p
      <0.001), and a greater waist-to-hip ratio (0.93 +/- 0.07 vs 0.91 +/- 0.07, p
      <0.001) than those with a CAC score of < or =10. Those with a CAC score >10 also
      tended to have a greater body mass index and larger subcutaneous fat area. After
      adjusting for traditional cardiovascular risk factors, however, only a large
      waist circumference (odds ratio 1.5, 95% confidence interval 1.04 to 2.0), a high
      total fat area (odds ratio 1.5, 95% confidence interval 1.1 to 2.1), and a high
      waist-to-hip ratio (odds ratio 1.6, 95% confidence interval 1.2 to 2.3) remained
      significantly associated with a CAC score >10. In conclusion, the measures of
      central obesity were more strongly associated with the CAC score than either the
      parameters assessing overall obesity or other more direct measures of visceral
      adiposity. These findings suggest that the total amount of central obesity is
      more important than the relative distribution of visceral versus subcutaneous
      fat.

PMID- 19766762
TI  - Effects of plant-based diets on plasma lipids.
AB  - Dyslipidemia is a primary risk factor for cardiovascular disease, peripheral
      vascular disease, and stroke. Current guidelines recommend diet as first-line
      therapy for patients with elevated plasma cholesterol concentrations. However,
      what constitutes an optimal dietary regimen remains a matter of controversy.
      Large prospective trials have demonstrated that populations following plant-based
      diets, particularly vegetarian and vegan diets, are at lower risk for ischemic
      heart disease mortality. The investigators therefore reviewed the published
      scientific research to determine the effectiveness of plant-based diets in
      modifying plasma lipid concentrations. Twenty-seven randomized controlled and
      observational trials were included. Of the 4 types of plant-based diets
      considered, interventions testing a combination diet (a vegetarian or vegan diet
      combined with nuts, soy, and/or fiber) demonstrated the greatest effects (up to
      35% plasma low-density lipoprotein cholesterol reduction), followed by vegan and
      ovolactovegetarian diets. Interventions allowing small amounts of lean meat
      demonstrated less dramatic reductions in total cholesterol and low-density
      lipoprotein levels. In conclusion, plant-based dietary interventions are
      effective in lowering plasma cholesterol concentrations.

PMID- 19766763
TI  - Mostly plants.

PMID- 19766764
TI  - Association of the parameters derived from the relation between RR intervals and
      left ventricle performance with a history of heart failure in patients with
      atrial fibrillation.
AB  - Parameters derived from the relation between RR intervals and left ventricular
      (LV) performance in atrial fibrillation (AF) have been useful to evaluate
      systolic LV function. This study investigated the association of these parameters
      with a history of heart failure. Echocardiography was performed in 107 patients
      with AF. LV outflow peak ejection velocity (Vpe) was adjusted for the effect of
      pre-preceding RR interval (RR-2) using the logarithmic equation between RR-2 and
      Vpe. The logarithmic equation between adjusted Vpe and preceding RR interval (RR
      1) was calculated in the co-ordinates with RR-1 from 0.6 to 1 second. From this
      equation, the ratio of slope to Vpe at RR-1 = 1 second (slope/Vpe-1) was
      obtained. When patients were divided into 2 groups according to a history of
      heart failure, old age, high slope/Vpe-1, mitral regurgitation, and left atrial
      enlargement independently predicted the occurrence of heart failure. Fractional
      shortening was not different between the 2 groups. In patients with normal LV
      size and without significant regurgitation (n = 69), old age and high slope/Vpe-1
      independently predicted the occurrence of heart failure. Areas under the receiver
      operating characteristics curve of slope/Vpe-1 for identifying heart failure were
      0.72 (p <0.000) and 0.74 (p <0.001) in all patients and in patients with normal
      LV size, respectively. In conclusion, the new parameter, slope/Vpe-1, was one of
      the most useful predictors for the occurrence of heart failure in AF and was
      superior to the classic hemodynamic parameters. This parameter might be
      determined not only by systolic function but also by diastolic function of the
      left ventricle.

PMID- 19766765
TI  - Impact of systemic hypertension on the diagnostic performance of B-type
      natriuretic peptide in patients with acute dyspnea.
AB  - Hypertension may affect the diagnostic performance of B-type natriuretic peptide
      (BNP). The objective of the present study was to assess the impact of a history
      of hypertension or blood pressure elevation on admission on the diagnostic
      performance of BNP in the diagnosis of heart failure (HF) in patients with acute
      dyspnea. BNP levels were measured using a rapid point-of-care device in 1,586
      patients with acute dyspnea. In patients with HF, BNP levels did not differ
      between those with and without histories of hypertension. Conversely, in patients
      without HF, a history of hypertension was associated with higher median BNP
      levels (38 pg/ml [interquartile range 13 to 119] vs 21 pg/ml [interquartile range
      7 to 64], p <0.001). The areas under the receiver-operating characteristic curves
      were 0.88 and 0.93 for those with and without histories of hypertension,
      respectively (p <0.001). Blood pressure elevation on admission did not affect the
      diagnostic accuracy of BNP (areas under the curve 0.90 in the 2 groups). In
      conclusion, although a history of hypertension is associated with higher BNP
      levels in patients with acute dyspnea without HF, the impact on the overall
      diagnostic performance of BNP is modest. Accordingly, BNP performs well as an
      indicator of HF in patients presenting in emergency departments regardless of a
      history of hypertension or elevated blood pressure on admission.

PMID- 19766766
TI  - Meta-analysis of prognostic value of stress testing in patients with asymptomatic
      severe aortic stenosis.
AB  - The management strategy in asymptomatic patients with severe aortic stenosis (AS)
      is controversial. Aortic valve replacement has significant morbidity and
      mortality, while there is a risk for sudden cardiac death with conservative
      management. There is no consensus on the prognostic value of stress testing to
      stratify management. A pooled analysis of studies in patients with severe AS was
      performed to assess the prognostic value of stress testing for adverse events,
      including angina, dyspnea, acute heart failure, sudden death, and symptoms
      requiring aortic valve replacement. A search of published research was performed
      using the terms "stress test" and "asymptomatic aortic stenosis." A random
      effects model was used to calculate pooled odds ratios and 95% confidence
      intervals. Data from 7 studies were included (491 patients with asymptomatic
      severe AS). None of the patients experienced any complications during or after
      stress testing. There were no sudden deaths in the patients with normal stress
      test results after 1 year of follow-up, while 5% with abnormal stress test
      results had sudden cardiac death. Overall, 52 of 253 patients (21%) with normal
      stress test results had adverse cardiac events, compared with 156 of 238 (66%)
      with abnormal stress test results (odds ratio 0.12, 95% confidence interval 0.07
      to 0.21, p <0.001). In conclusion, stress testing in asymptomatic patients with
      severe AS is safe and identifies patients at risk for adverse cardiac events and
      sudden cardiac death. These data suggest that stress tests can be used for risk
      stratification and for deciding on the timing of aortic valve replacement in
      asymptomatic patients with severe AS.

PMID- 19766767
TI  - Direct measurement of vena contracta area by real-time 3-dimensional
      echocardiography for assessing severity of mitral regurgitation.
AB  - We tested the hypothesis that the vena contracta (VC) cross-sectional area in
      patients with mitral regurgitation (MR) can be reproducibly measured by real-time
      3-dimensional (3D) echocardiography and correlates well with the volumetric
      effective regurgitant orifice area (EROA). Earlier MR repair requires accurate
      noninvasive measures, but practically, the VC area is difficult to image in 2
      dimensional views, which are often oblique to it. 3D echocardiography can provide
      an otherwise unobtainable true cross-sectional view. In 45 patients with mild or
      greater MR, 44% eccentric, 2-dimensional and 3D VC areas were measured and
      correlated with the EROA derived from the regurgitant stroke volume. Real-time 3D
      echocardiography of the VC area correlated and agreed well with the EROA for both
      central and eccentric jets (r(2) = 0.86, SEE 0.02 cm(2), difference 0.04 +/- 0.06
      cm(2), p = NS). For eccentric jets, 2-dimensional echocardiography overestimated
      the VC width compared with 3D echocardiography (p = 0.024) and correlated more
      poorly with the EROA (r(2) = 0.61 vs 0.85, p <0.001), causing clinical
      misclassification in 45% of patients with eccentric MR. The interobserver
      variability for the 3D VC area was 0.03 cm(2) (7.5% of the mean, r = 0.95); the
      intraobserver variability was 0.01 cm(2) (2.5% of the mean, r = 0.97). In
      conclusion, real-time 3D echocardiography accurately and reproducibly quantified
      the vena contracta cross-sectional area in patients with both central and
      eccentric MR. Rapid acquisition and intuitive analysis promote practical clinical
      application of this central, directly visualized, measure and its correlation
      with outcome.

PMID- 19766768
TI  - Electrocardiographic characteristics at initial diagnosis in patients with
      isolated left ventricular noncompaction.
AB  - Isolated ventricular noncompaction (IVNC) is a primary cardiomyopathy
      characterized by a specific morphologic pattern. Patients with IVNC can develop
      various arrhythmic complications such as life-threatening ventricular
      arrhythmias, as well as heart failure or systemic embolic events. The present
      study was designed to comprehensively analyze the electrocardiographic (ECG)
      pattern at the initial diagnosis in patients with IVNC and to investigate their
      correlation with the clinical features and echocardiographic findings.
      Electrocardiograms from the initial diagnosis of IVNC were available for 78
      patients from March 1995 to November 2008. The most common findings were
      intraventricular conduction delay (especially left bundle branch block), voltage
      signs of left ventricular (LV) hypertrophy, and repolarization abnormalities. An
      entirely normal electrocardiogram was present in 10 subjects (13%). However, no
      ECG findings or patterns specific for IVNC were found. A striking overlap was
      observed between the presence of intraventricular conduction delay (left bundle
      branch block, in particular), atrial conduction delay (PR interval prolongation
      or atrioventricular block), and prolongation of the QTc and reduced systolic LV
      function and LV/left atrial dilation. Moreover, patients with ECG voltage signs
      of LV hypertrophy more often presented with, or had a history of, systemic
      embolic events. In conclusion, our results have provided a comprehensive analysis
      of ECG findings of patients newly diagnosed with IVNC. Although intraventricular
      conduction delay, repolarization abnormalities, and LV hypertrophy are frequently
      present, no ECG patterns specific for IVNC at the first presentation with the
      disease were found. Whether these findings have prognostic implications needs to
      be investigated in long-term controlled studies.

PMID- 19766769
TI  - Frequencies and types of arrhythmias in patients with systemic light-chain
      amyloidosis with cardiac involvement undergoing stem cell transplantation on
      telemetry monitoring.
AB  - Cardiac patients with systemic light-chain amyloidosis have a high incidence of
      arrhythmias and arrhythmia-related death. We aimed to describe the arrhythmias,
      determine patient characteristics associated with the development of ventricular
      arrhythmias, and the utility of telemetric monitoring in patients with cardiac
      involvement due to AL amyloidosis undergoing stem cell transplantation (SCT).
      Arrhythmia events of 24 consecutive cardiac patients with AL who underwent SCT
      with continuous telemetric monitoring were retrospectively reviewed. The relation
      between number and severity of ventricular arrhythmias (ventricular
      tachycardia/ventricular fibrillation [VT/VF]) and baseline clinical, laboratory,
      and echocardiographic data were determined. Atrial and ventricular arrhythmias
      were found in all patients. Nonsustained VT was the most frequent event (267
      total events). Therapeutic intervention for arrhythmias was required in 20
      patients; in 3 patients, life-threatening arrhythmias were detected and treated.
      There was an inverse relation between VT/VF and cardiac output (r = -0.72, p
      <0.0001), cardiac index (r = -0.71, p = 0.0001), and stroke volume (r = -0.59, p
      = 0.0029). There was also a relation between VT/VF and brain natriuretic peptide
      before SCT (r = 0.47, p = 0.019) and average brain natriuretic peptide levels
      during admission for SCT (r = 0.62, p = 0.0012), troponin I levels at diagnosis
      (r = 0.47, p = 0.022), and serum creatinine levels before SCT (r = 0.62, p =
      0.001). In conclusion, patients with cardiac amyloidosis undergoing SCT have a
      high incidence of ventricular and atrial arrhythmias; decreased cardiac output
      was strongly associated with significant ventricular arrhythmias. Continuous
      telemetric monitoring contributed to patient safety during SCT.

PMID- 19766770
TI  - Apoptosis in patients with acute myocarditis.
AB  - Acute myocarditis is an acute inflammatory syndrome characterized by acute
      myocardial damage and dysfunction followed by a variable recovery over time with
      some patients progressing toward severe dilated cardiomyopathy. Cardiomyocyte
      apoptosis, a key pathologic feature of heart failure, may play a critical role in
      functional recovery in patients with acute myocarditis. The aim of the study was
      to investigate whether apoptosis predicts functional recovery in patients with
      acute myocarditis. Sixteen patients with biopsy-documented acute myocarditis were
      followed for 1 year with serial transthoracic echocardiography. Functional
      recovery was defined as 12-month left ventricular ejection fraction >40%.
      Cardiomyocyte apoptosis, leukocyte infiltration, and cell proliferation was
      assessed in all samples. A group of cases in which the diagnosis of acute
      myocarditis was made after death was also selected for comparison, and
      morphologically normal hearts from patients who died from a noncardiac cause were
      selected as controls. Six patients (38%) had functional recovery at 12 months,
      whereas 10 (62%) did not. The 2 groups had similar characteristics except for
      lower baseline left ventricular ejection fraction in the group with functional
      recovery. Apoptotic rate was found to be significantly higher in patients with
      acute myocarditis than in control hearts, and, unexpectedly, patients with
      functional recovery had significantly higher apoptotic rates than patients
      without recovery (3.2% vs 0.5%, p = 0.001). None of the patients with apoptotic
      rates below the median had functional recovery versus 86% of patients with
      apoptotic rates above the median (p <0.001). In conclusion, higher rates of
      cardiomyocyte apoptosis in patients with acute myocarditis are associated with
      functional recovery at 1 year.

PMID- 19766771
TI  - Risk of aortic root or ascending aorta complications in patients with bicuspid
      aortic valve with and without coarctation of the aorta.
AB  - The actual incidence of ascending aorta complications (AACs) in adults with
      bicuspid aortic valve (BAV) and the role of associated coarctation of the aorta
      (COA) as an independent risk factor for AACs remain unknown. From the Adult
      Congenital Heart Disease database at La Paz Hospital, 631 patients in whom a BAV
      was diagnosed by echocardiography or surgical inspection since December 1989 were
      identified. These patients were then further subdivided into 2 groups according
      to the presence of an associated COA. AACs included aortic aneurysms (ascending
      aorta > or =55 mm) and aortic dissection, rupture, or perforation. Patients with
      a BAV and COA had a greater prevalence of AACs (8.0%) than those with an isolated
      BAV (3.7%; p = 0.037). The coexistence of COA was the only significant predictor
      of AACs (odds ratio 4.7, 95% confidence interval 1.5 to 15; p = 0.01). From the
      total patient group with a BAV, the clinical and echocardiographic data were
      reviewed for 341 patients without an AAC at baseline (97 with and 244 without
      COA) who had undergone serial examinations >1 year apart. The median follow-up
      was 7 years (interquartile range 3.5 to 10.2; total 2,436 patient-years). A new
      AAC occurred in 13 patients (0.5/100 patient-years). The incidence of AACs was
      1.3/100 patient-years in the COA group versus 0.2/100 patient-years in the non
      COA group (hazard ratio 7.5, 95% confidence interval 2.0 to 28, p = 0.002). All
      acute aortic events (dissection or rupture) at follow-up occurred in patients
      with a BAV and COA. In conclusion, the long-term incidence of AACs in patients
      with isolated BAV is low, but patients with BAV and associated COA are at
      increased risk.

PMID- 19766772
TI  - Determinants of exercise capacity after arterial switch operation for
      transposition of the great arteries.
AB  - Patients who undergo the arterial switch operation for transposition of the great
      arteries (TGA) are at risk of reduced exercise capacity, with most reports
      focusing on chronotropic incompetence as the cause. Residual right ventricular
      outflow tract (RVOT) obstruction is relatively common after the arterial switch
      operation, but its effect on exercise capacity is unknown. We studied 60 patients
      (44 males, age 13.3 +/- 3.4 years) who had undergone a neonatal arterial switch
      operation using the cardiopulmonary exercise test and transthoracic
      echocardiography. The peak exercise oxygen uptake (VO(2)), and heart rate were
      recorded and are expressed as the percentage of predicted values. The greatest
      velocity detected by echocardiography across the pulmonary valve, pulmonary
      trunk, or pulmonary branches was used in the analysis as an index of RVOT
      obstruction. The peak VO(2)% was 84 +/- 15%, and the peak heart rate percentage
      was 97 +/- 8%. Of the 60 patients, 29 had an abnormal peak VO(2)% (< or =84%) and
      3 (5%) had an abnormal peak heart rate percentage (< or =85%). The maximal RVOT
      velocity was 2.3 +/- 0.6 m/s, and it correlated with the peak VO(2)% (r = -0.392,
      p = 0.004). On multivariate analysis, the presence of residual RVOT obstruction
      (p = 0.0007) was the only variable associated with a reduced peak VO(2)%.
      Patients with a RVOT maximal velocity > or =2.5 m/s had a lower peak VO(2)% than
      those with lower velocities (p <0.0001). No relation was found between age at
      testing and the peak VO(2)%. In conclusion, a reduced exercise capacity is
      relatively common in children and young adults who have undergone an arterial
      switch operation, but it does not decrease with age. The presence of residual
      RVOT obstruction seems to have an effect on exercise capacity.

PMID- 19766773
TI  - Percutaneous device closure of iatrogenic left ventricular wall pseudoaneurysm.
AB  - A 67-year-old man with ischemic cardiomyopathy was transferred to our hospital in
      cardiogenic. During a video-assisted mini-thoracotomy for left ventricular
      epicardial lead implantation, a left ventricular free-wall rupture occurred and
      an emergency surgical repair was performed. Postoperatively patients experience
      left ventricular wall pseudoaneurysm. After stabilization of clinical conditions
      with aggressive medical treatment, we decided to attempt a minimally invasive
      procedure (ie, a transcatheter pseudoaneurysm closure). To date, few cases of
      device closure of left ventricle pseudoaneurysm are reported in the literature,
      usually secondary to myocardial infarction, and we believe this is the first case
      of left ventricle pseudoaneurysm after iatrogenic left ventricle laceration and
      surgical closure.

PMID- 19766774
TI  - Ross procedure with a composite autograft using stretch Gore-Tex material.
AB  - In an attempt to allow physiologic expansion of the pulmonary autograft, yet
      limit late root dilation, we used stretch Gore-Tex material (W. L. Gore & Assoc,
      Flagstaff, AZ) as an external wrap. Follow-up cardiac computed tomography with
      reconstructed three-dimensional and dynamic images confirmed normal "triple
      bulge" sinus Valsalva geometry and preserved natural systolic expansion of the
      neoaortic root.

PMID- 19766775
TI  - Lung resection for treatment of idiopathic thrombocytopenic purpura associated
      with a pulmonary lymphoma.
AB  - Most primary lymphomas of the lung arise from the mucosa-associated lymphoid
      tissue of the bronchus. Autoimmune phenomena are associated with non-Hodgkin's
      lymphoma; among them immune thrombocytopenia is one of the most rare. In this
      study we report an extremely rare case of a patient with primary pulmonary mucosa
      associated lymphoid tissue lymphoma associated with autoimmune thrombocytopenic
      purpura, with rapid restoration of normal platelet count after lung resection.

PMID- 19766776
TI  - Primary myelolipoma of the chest wall.
AB  - Myelolipoma is a rare neoplasm composed of an admixture of mature adipose tissue
      and hematopoietic elements. It typically occurs in adrenal glands as a solitary,
      well-circumscribed mass, and the thoracic location is extremely unusual. We
      present a 63-year-old man with an accidentally detected tumor of the chest wall.
      Thoracoscopic resection and subsequent histopathologic examination of the lesion
      revealed myelolipoma with bony spicules, which are an unusual component in this
      neoplasm. We discuss the etiology, histopathology, differential diagnosis, and
      recommended management of extra-adrenal myelolipoma, and we conclude that it
      should be considered in the differential diagnosis of subpleural chest wall
      tumors.

PMID- 19766777
TI  - Skin depigmentation: could it be a complication caused by thoracic sympathectomy?
AB  - Primary hyperhidrosis is an idiopathic disorder, and its definitive treatment is
      obtained through thoracic sympathectomy. However, this procedure is not exempt
      from complications and compensatory sweating is the main inconvenience described.
      In this article, 2 patients were submitted to video-assisted thoracoscopic
      sympathectomy, and after approximately 8 months they noticed depigmentation of
      the region corresponding to the blockage of sympathetic stimulus. This fact could
      be explained by the possible effect of the nervous system on the melanocytes of
      human skin. Thus, patients with primary hyperhidrosis, who are candidates for
      thoracic sympathectomy and have brown skin, must be made aware of this possible
      complication.

PMID- 19766778
TI  - Unusual "single coronary" anatomy in transposition of the great arteries.

PMID- 19766779
TI  - Giant inflammatory myofibroblastic tumor of esophagus.

PMID- 19766780
TI  - A new no-touch aorta technique for arterial-source, off-pump coronary surgery.
AB  - The possibility of avoiding the manipulation of the ascending aorta plays a key
      role in the neuroprotective effect of off-pump coronary revascularization,
      reducing the overall invasiveness. We have devised a new surgical plan using the
      proximal stump of the right internal thoracic artery as an intrathoracic,
      arterial source of flow for the saphenous vein, avoiding direct aorta
      manipulation. The saphenous vein can be as long as required, and its proximal
      anastomosis guarantees a better match of the two conduits and undergoes a lower
      peak pressure.

PMID- 19766781
TI  - Saving lives is more important than abstract moral concerns: financial incentives
      should be used to increase organ donation.

PMID- 19766782
TI  - The impact of center volume on survival in lung transplantation: an analysis of
      more than 10,000 cases.
AB  - BACKGROUND: Whether center volume influences outcomes in lung transplantation is
      unknown. We reviewed United Network for Organ Sharing data to examine the effect
      of center volume on short-term mortality. METHODS: We reviewed United Network for
      Organ Sharing data (1998 through 2007) to identify 10,496 first-time adult lung
      transplantation recipients at 79 centers. Centers were stratified by quartiles of
      mean annual volume. Risk of 30-day mortality and 1- and 5-year mortality
      (censored for 30-day death) were assessed by multivariable Cox proportional
      hazards regression. RESULTS: Mean center volume ranged from less than 1 to 58.2
      (median, 9.4 cases/year; volume quartiles: 0 to 2.1, 2.2 to 9.4, 9.5 to 19.9, and
      20 to 58.2 cases). Each 1 case/year decrease led to a 2% increase in 30-day
      mortality (hazard ratio, 1.02; 95% confidence interval, 1.01 to 1.02; p < 0.001).
      Centers of lowest quartile (performing <or=2.1 lung transplantations/year) had a
      30-day cumulative mortality of 9.6% or 89% increase in the risk of death (hazard
      ratio, 1.89; 95% confidence interval, 1.01 to 3.44; p = 0.05) compared with the
      highest quartile centers despite fewer idiopathic pulmonary fibrosis patients
      (15.6% versus 25.8%; p < 0.001) and younger age (40.9 versus 51.5 years; p <
      0.001). Low-volume centers had double the risk of 30-day censored 1-year
      mortality (hazard ratio, 1.95; 95% confidence interval, 1.30 to 2.92; p = 0.001).
      High-volume centers (>or=20 lung transplantations/year) had the lowest 30-day
      mortality (4.1%). CONCLUSIONS: We provide an initial examination of the
      relationship of volume and lung allocation score to outcomes for lung
      transplantation. Low center volume is associated with increased short-term and
      cumulative mortality despite fewer idiopathic pulmonary fibrosis patients and
      younger patients.

PMID- 19766783
TI  - The role of adenosine A2A receptor signaling in bronchiolitis obliterans.
AB  - BACKGROUND: Binding of adenosine to the anti-inflammatory Gs-coupled adenosine 2A
      receptor (A(2A)R) inhibits the activity of most inflammatory cells. Extensive
      preclinical evidence exists for the use of A(2A)R agonists in the prevention of
      acute ischemia-reperfusion injury. Activation of A(2A)Rs on lymphocytes and
      antigen-presenting cells also attenuates the alloimmune response. Because
      ischemia-reperfusion injury and alloimmunity are risk factors for the development
      of bronchiolitis obliterans (BO), the objective of this study was to determine
      the effect of A(2A)R signaling on tracheal rejection in a mouse model of BO.
      METHODS: A non-revascularized heterotopic tracheal model across a total
      alloantigenic mismatch was used to study A(2A)R signaling in a mouse model of BO.
      Tracheal transplants were performed using Balb/c donors into wild-type or A(2A)R
      knockout C57BL/6 recipient mice. Another group of Balb/c transplants into C57BL/6
      recipients were also treated with a selective A(2A)R agonist. Tracheas were
      assessed at 3, 7, 12, 21, and 28 days after transplantation by hematoxylin and
      eosin staining, immunohistochemical staining, and collagen staining. RESULTS:
      Compared with allograft tracheas in wild-type recipients, allografts in A(2A)R
      knockout recipients had increased inflammation and more severe BO development.
      Recipient wild-type mice treated with a selective A(2A)R agonist were
      significantly protected from lymphocyte infiltration and luminal occlusion, but
      fibro-obliteration still developed by 28 days after transplantation. CONCLUSIONS:
      Endogenous adenosine signals through the A(2A)R to attenuate inflammatory and
      immune factors involved in BO development. Synthetic A(2A)R agonists may provide
      a novel treatment strategy to prevent BO.

PMID- 19766784
TI  - Risk of pneumonectomy after induction therapy for locally advanced non-small cell
      lung cancer.
AB  - BACKGROUND: Recent data from prospective multimodality trials have documented an
      unacceptable early mortality with pneumonectomy after induction chemotherapy.
      This finding has raised skepticism toward pneumonectomy as a surgical option for
      patients with regionally advanced nonsmall-cell lung cancer. In the current
      study, perioperative outcomes after pneumonectomy with or without neoadjuvant
      therapy are compared to determine the impact of induction therapy on
      perioperative mortality in this setting. Variables associated with increased
      perioperative risk are identified. METHODS: A review of 315 nonsmall-cell lung
      cancer patients (196 male [62%]) undergoing pneumonectomy over a 15-year period
      was undertaken. Patients were well matched for clinical variables other than
      receiving induction chemotherapy. Complications and operative mortality were
      analyzed for associations with laterality and induction chemotherapy. RESULTS:
      Median age was 64 years, (range, 25 to 82). Age was predictive of mortality in 13
      of 86 patients (15%) more than 70 years old, compared with 16 of 229 patients
      (7%) less than 70 years old (hazard ratio = 1.77, p = 0.046). Overall operative
      mortality was 9.2% (29 of 315). There were 115 left-sided (37%) and 200 right
      sided (63%) pneumonectomies. Sixty-eight patients (22% [left = 31, right = 37])
      received induction chemotherapy. Surgery alone was performed in 247 patients.
      Mortality among patients undergoing induction chemotherapy was 21% (odds ratio =
      4.01; p = 0.0007). After induction chemotherapy, postoperative bronchopleural
      fistula associated with respiratory failure was predictive of operative mortality
      (hazard ratio = 148, p = 0.0001). Left-side pneumonectomy did appear to a have a
      greater incidence of postoperative arrhythmia. CONCLUSIONS: Morbidity and
      mortality after pneumonectomy is substantial. Patients greater than 70 years old
      appear to be at increased risk. Induction chemotherapy also increases the risk of
      operative mortality after pneumonectomy. Patients should be advised of this
      increased operative risk, and the multidisciplinary team must consider this when
      pneumonectomy appears necessary after induction therapy for locally advanced
      nonsmall-cell lung cancer.

PMID- 19766785
TI  - Is thoracoscopic pneumonectomy safe?
AB  - BACKGROUND: While thoracoscopic surgical lobectomy is an established operation,
      the safety of thoracoscopic pneumonectomy (TP) is uncertain. METHODS: From
      January 1, 2002, to September 30, 2008 at a comprehensive cancer center, 70
      patients underwent pneumonectomy. Three patients were excluded for emergent
      operations. Thoracoscopic pneumonectomy was completed successfully in 24 patients
      and attempted in 8 others (25% conversion rate). Analysis was done on an
      intention-to-treat basis. RESULTS: By 2008, 75% of pneumonectomy cases were
      planned as TP while there were no conversions to thoracotomy. There was no
      difference in median blood loss between patients undergoing TP versus thoracotomy
      (325 vs 300 mL, p = 0.52), but operations were longer (286 vs 228 minutes, p <
      0.01). Median intensive care unit stay was 2 days in both groups and median
      hospital stay was 5.0 days in the TP group versus 6.0 days in the thoracotomy
      group (p = 0.28). Major complications were similar between groups. The TP
      reoperations were for bleeding (2), bronchopleural fistula (2), empyema (1), and
      chylothorax (1). The only TP death occurred in an 83-year-old patient from
      respiratory failure. Neither the use of adjuvant therapy nor the time between
      surgery and commencement of adjuvant therapy was different between groups.
      Conversions alone compared with patients undergoing thoracotomy were associated
      with a moderate increase in blood loss and intensive care unit stay, but not in
      any major complications. CONCLUSIONS: Thoracoscopic pneumonectomy can be done
      safely. The availability of this option is important especially in an era of
      multimodality therapy as more debilitated patients present for surgical therapy.

PMID- 19766786
TI  - Risk factors for morbidity after lobectomy for lung cancer in elderly patients.
AB  - BACKGROUND: Studies evaluating risk factors for complications after lobectomy in
      elderly patients have not adequately analyzed the effect of using minimally
      invasive approaches. METHODS: A model for morbidity including published
      preoperative risk factors and surgical approach was developed by multivariable
      logistic regression. All patients aged 70 years or older who underwent lobectomy
      for primary lung cancer without chest wall resection or airway procedure between
      December 1999 and October 2007 at a single institution were reviewed.
      Preoperative, histopathologic, perioperative, and outcome variables were assessed
      using standard descriptive statistics. Morbidity was measured as a patient having
      any perioperative complication. The impact of bias in the selection of surgical
      approach was assessed using propensity scoring. RESULTS: During the study period,
      338 patients older than 70 years (mean age, 75.7 +/- 0.2) underwent lobectomy
      (219 thoracoscopy, 119 thoracotomy). Operative mortality was 3.8% (13 patients)
      and morbidity was 47% (159 patients). Patients with at least one complication had
      increased length of stay (8.3 +/- 0.6 versus 3.8 +/- 0.1 days; p < 0.0001) and
      mortality (6.9% [11 of 159] versus 1.1% [2 of 179]; p = 0.008). Significant
      predictors of morbidity by multivariable analysis included age (odds ratio, 1.09
      per year; p = 0.01) and thoracotomy as surgical approach (odds ratio, 2.21; p =
      0.004). Thoracotomy remained a significant predictor of morbidity when the
      propensity to undergo thoracoscopy was considered (odds ratio, 4.9; p= 0.002).
      CONCLUSIONS: Patients older than 70 years of age can undergo lobectomy for lung
      cancer with low morbidity and mortality. Advanced age and the use of a
      thoracotomy increased the risk of complications in this patient population.

PMID- 19766787
TI  - Invited commentary.

PMID- 19766788
TI  - TNM stage is the most important determinant of survival in metachronous lung
      cancer.
AB  - BACKGROUND: Distinguishing a metachronous lung cancer from a metastatic or
      recurrent lesion in patients with a prior history of non-small cell lung cancer
      is a challenging task. Previous studies have suggested histologic type and
      disease-free interval as criteria for diagnosing metachronous lung cancer. These
      factors may not be as relevant now that current imaging allows for earlier
      detection of tumors and with the rising incidence of adenocarcinoma. The purpose
      of this study was to reexamine the factors that determine outcomes in patients
      with a second primary lung cancer. METHODS: A retrospective review of a
      prospective lung cancer database was performed to identify patients with
      metachronous lung cancer. Metachronous lung cancer was defined as any non-small
      cell lung cancer occurring after a prior resection regardless of disease-free
      interval or histologic type. The Kaplan-Meier method was used for survival
      analysis. The Mantel-Cox method was used to compare overall survival. Cox
      regression was used for multivariate analysis. RESULTS: Fifty-eight patients had
      metachronous lung cancer. Overall survival at 5 years was 66% (stage IA, 74%; IB,
      59%; all other stages, 0%; p = 0.01). Seventy-two percent (42 of 58 patients) had
      similar histologic type. There was no difference in overall survival based on
      similar versus different histologic type (65% versus 73%; p = 0.77). Median
      disease-free interval was 42 months (range, 8 to 312 months). Disease-free
      interval was not a significant predictor of overall survival (p = 0.24). The
      extent of resection included wedge (36%, 21 of 58 patients), segmentectomy (24%,
      14 of 58 patients), and lobectomy (40%, 23 of 58 patients), with no difference in
      overall survival (58% versus 60% versus 75%, respectively; p = 0.32).
      CONCLUSIONS: These data suggest that early tumor stage is the only significant
      determinant of survival after surgical treatment of metachronous lung cancer.
      Neither histologic type nor disease-free interval was of prognostic value.
      Limited resections may be adequate treatment.

PMID- 19766789
TI  - Limited resection for noninvasive bronchioloalveolar carcinoma diagnosed by
      intraoperative pathologic examination.
AB  - BACKGROUND: The establishment of limited resection procedures for non-small cell
      lung cancer is expected. Many groups have suggested noninvasive
      bronchioloalveolar carcinoma (BAC) to be a potential indication for limited
      resection. METHODS: We designed a prospective phase II study evaluating limited
      resection for noninvasive BAC diagnosed by intraoperative pathologic examination.
      From 1999 to 2007, limited resection was the procedure in 46 patients (16 men and
      30 women; median age, 69 years; range, 49 to 83) who were diagnosed
      intraoperatively as having noninvasive BAC. The first end point was the
      predictive value of the intraoperative pathologic examination for noninvasive BAC
      diagnosis. The second end point was overall survival, disease-free survival, and
      cancer-specific survival, calculated using the Kaplan-Meier method. RESULTS: We
      performed wedge resections for 44 patients and segmentectomy for 2 patients.
      Permanent pathologic examination revealed 3 patients had primary lung
      adenocarcinomas other than noninvasive BAC. The predictive value of
      intraoperative pathologic examination for noninvasive BAC diagnosis was 94%.
      During a median 51-month follow-up, there were only 2 cancer unrelated deaths.
      The 5-year overall survival rate and the disease-free survival rate were 93%, and
      the 5-year cancer-specific survival rate was 100%. CONCLUSIONS: The results of
      our prospective phase II study indicate that limited resection, mainly by wedge
      resection, is a potentially curative surgical procedure and may be an acceptable
      alternative to lobectomy for patients with noninvasive BAC. Furthermore, an
      intraoperative pathologic diagnosis of noninvasive BAC is strongly predictive and
      allows for an intraoperative decision to perform a limited resection in these
      patients.

PMID- 19766790
TI  - Invited commentary.

PMID- 19766791
TI  - Long-term follow-up of the functional and physiologic results of diaphragm
      plication in adults with unilateral diaphragm paralysis.
AB  - BACKGROUND: Patients with lifestyle-limiting dyspnea attributable to unilateral
      diaphragm paralysis have been shown to experience a decrease in their dyspnea and
      an improvement in their pulmonary spirometry and functional status with diaphragm
      plication acutely after surgery. This investigation summarizes these patients'
      outcomes with long-term follow-up. METHODS: Adult patients undergoing plication
      of the hemidiaphragm for lifestyle-limiting dyspnea secondary to unilateral
      diaphragm paralysis were assessed preoperatively, 6 month after surgery and then
      annually using the Medical Research Council dyspnea score, pulmonary spirometry,
      activities of daily living questionnaire, and a chest radiograph. Patients with
      at least 48 months of follow-up were included in this investigation. RESULTS:
      Forty-one patients underwent plication of the hemidiaphragm through video
      assisted thoracoscopy (30) or thoracotomy (11). Mean follow-up was 57 +/- 10
      months. Mean forced vital capacity, forced expiratory volume at 1 second,
      functional residual capacity, and total lung capacity all improved by 19%, 23%,
      21%, and 19% (p < 0.005), respectively, when measured 6 months after surgery, as
      were mean Medical Research Council dyspnea scores (p < 0.0001). These mean values
      remained constant over the follow-up period. Four patients did not show
      improvement in their Medical Research Council dyspnea scores nor functional
      status despite improvements in their pulmonary spirometry values. Two of these
      patients had a body mass index greater than 35 kg/m(2) and 3 had documented
      unilateral diaphragm paralysis for at least 4 years before plication.
      CONCLUSIONS: Plication of the hemidiaphragm produces improvement for the vast
      majority of patients in pulmonary spirometry, dyspnea, and functional status that
      endures over long-term follow-up. Patients who are morbidly obese or who have
      longstanding unilateral diaphragm paralysis may not realize the same benefits of
      plication.

PMID- 19766792
TI  - Serum protein profiles in myasthenia gravis.
AB  - BACKGROUND: The diagnosis of myasthenia gravis (MG) remains challenging. We
      performed a proteome-wide search for potential serum protein diagnostic markers
      for MG using surface-enhanced laser desorption/ionization (SELDI) time-of-flight
      mass spectrometry (TOFMS). METHODS: Proteomic spectra from 80 MG patients and 80
      healthy individuals were generated by SELDI. Samples from 56 MG patients and 56
      healthy individuals in the training set were analyzed to set up the decision
      tree. Samples from 24 MG patients and 24 healthy individuals were used for cross
      validation testing. RESULTS: The SELDI TOFMS analysis generated 101 peaks,
      representing differentially expressed proteins between 1000 and 20000 Da. Among
      them, 9 peaks were down-regulated and 30 others were up-regulated in the MG sera
      compared with the controls. The decision tree used the peak at M4168.94 Da and
      M1122.57 Da as splitters in the classification process. In the training set, 112
      samples were classified as MG or control group, with a sensitivity of 100% and
      specificity of 89.3%; the 10-fold cross-validated analysis identified the optimal
      decision tree with the lowest relative cross-validated cost of 0.080. In the test
      set, the decision tree generated was able to identify 20 of 24 MG patients and 21
      of 24 healthy individuals with a sensitivity of 83.3% and a specificity of 87.5%.
      CONCLUSIONS: SELDI TOFMS is a useful tool for the detection and identification of
      potential serum biomarkers that can diagnose MG with high sensitivity and
      specificity.

PMID- 19766793
TI  - Invited commentary.

PMID- 19766794
TI  - Risk factors for 24-hour mortality after traumatic rib fractures owing to motor
      vehicle accidents: a nationwide population-based study.
AB  - BACKGROUND: Accurate identification of patients at high risk of death as a result
      of major chest trauma is essential within a trauma system. We used 3-year
      population-based data in Taiwan to evaluate risk factors associated with 24-hour
      mortality among adults with obvious rib fractures and needing hospitalization
      after traffic accidents. METHODS: Pooled data from Taiwan's National Health
      Insurance Research Database for the years 2002 through 2004 were used. A total of
      18,856 patients hospitalized with rib fractures after traffic accidents were
      included. Multivariate logistic regression using generalized estimating equations
      was performed to explore the relationship between 24-hour mortality and patients'
      age, sex, and comorbid conditions, as well as hospital characteristics, adjusting
      for social factors and any clustering of the sampled patients by hospital.
      RESULTS: Of patients in the sample, 459 (2.4%) died within 24 hours of admission.
      Patients who had six or more rib fractures were three times more likely to die
      within 24 hours of admission compared with patients with only one rib fracture
      (odds ratio [OR], 3.16; p < 0.001). The adjusted odds of death within 24 hours
      were higher for patients who had hemopneumothorax (OR, 3.15; p < 0.001),
      extremity fractures (OR, 1.74; p < 0.001), pelvic fractures (OR, 2.92; p <
      0.001), head injuries (OR, 4.29; p < 0.001), spleen injury (OR, 1.83; p < 0.05),
      hepatic injury (OR, 4.39; p < 0.001), heart injury (OR, 4.48; p < 0.001), and
      diaphragm injury (OR, 3.16; p < 0.05) compared with patients who had none of
      these injuries. CONCLUSIONS: We concluded that more than six ribs fractured,
      heart injuries, hepatic injuries, head injuries, and advanced age are the most
      important determinants of 24-hour mortality after thoracic trauma from traffic
      accidents.

PMID- 19766795
TI  - Open window thoracostomy treatment of empyema is accelerated by vacuum-assisted
      closure.
AB  - BACKGROUND: Recurrent thoracic empyema in the presence of residual lung tissue
      can be treated with an open window thoracostomy (OWT). Vacuum-assisted closure
      (VAC) of these large thoracic defects is a novel option. METHODS: Nineteen
      patients with residual lung tissue received an OWT for treatment of recurrent
      thoracic empyema. In this retrospective case series, 8 patients (aged 58 +/- 20
      years, all male) were treated conventionally, and 11 patients (aged 53 +/- 17
      years, 8 male) were treated with VAC. RESULTS: The application of the VAC system
      resulted in rapid debridement of the thoracic cavity and reexpansion of the
      residual lung tissue. The duration of OWT and VAC therapy was 39 +/- 17 and 31 +/
      19 days, respectively. All 11 patients were amenable for subsequent closure
      using pedicled muscular flaps. In 2 patients, VAC therapy alone resulted in
      complete closure of the OWT. The average duration of follow-up was 46 +/- 19
      months. All patients, except 1, have recovered well. One patient died of
      nonpulmonary causes. In the non-VAC group (n = 8), the OWT was managed
      conventionally by application of saline-soaked gauzes. In 2 patients, the OWT was
      eventually closed using pedicled muscular flaps (after 75 and 440 days,
      respectively). Four patients died of OWT-related complications (1 bleeding, 3
      recurrent infections) during follow-up; 1 patient died of a cause unrelated to
      OWT. The average duration of OWT was 933 +/- 1,422 days. CONCLUSIONS: When
      compared with conventional management of OWT, VAC therapy accelerates wound
      healing and improves reexpansion of residual lung tissue in patients with OWT
      after empyema, allowing rapid surgical closure.

PMID- 19766796
TI  - Invited commentary.

PMID- 19766797
TI  - Comparison of ultrasonic scalpel to electrocautery in patients undergoing
      endoscopic thoracic sympathectomy.
AB  - BACKGROUND: Sympathectomy is an effective treatment for hyperhidrosis. The
      ultrasonic scalpel and electrocautery have been used for the procedure, but the
      use of the ultrasonic scalpel has been promoted as superior to that of
      electrocautery. This study explored whether a reusable electrocautery probe was
      equally as effective and safe as the ultrasonic scalpel for sympathectomy.
      METHODS: We retrospectively analyzed 140 consecutive patients. The ultrasonic
      scalpel (HDH 05, Ethicon Endo-Surgery, Cincinnati, OH) was used in 70 patients
      (group 1) and a reusable 5-mm cautery hook (Edlo, Canoas, Brazil) was used in 70
      patients (group 2). End points were improvement in symptoms (% improvement
      score), length of stay, return to work, and complications. Data were analyzed
      using two-tailed t test and the chi(2) (p = 0.05 was significant). Data are mean
      +/- standard deviation. RESULTS: Follow-up was 27.2 +/- 8.4 months. Groups were
      similar in demographics, disease site, and level of sympathectomy. There was no
      significant difference in improvement score by site. The feet had the least
      improvement score (36.5% +/- 32.3%), and the hands the highest improvement score
      (97.0% +/- 11.3%). Length of stay was similar, 11.4 +/- 5.9 (group 1) vs 10.1 +/-
      5.4 hours (group 2). Return to work in group 1 was 4.8 +/- 2.7 vs 5.7 +/- 3.6
      days (p = 0.09). Group 1 had 14 complications and group 2 had 7 (p = 0.16).
      CONCLUSIONS: We could not demonstrate a clear advantage in the use of the
      ultrasonic scalpel.

PMID- 19766798
TI  - Off-pump coronary artery bypass disproportionately benefits high-risk patients.
AB  - BACKGROUND: It is not known which patient subgroups may benefit most from off
      pump coronary artery bypass grafting (OPCAB) rather than coronary artery bypass
      grafting on cardiopulmonary bypass (CPB). METHODS: The Society of Thoracic
      Surgeons database was queried for all isolated, primary coronary artery bypass
      graft cases between January 1, 1997, and December 31, 2007, at a US academic
      center. The Society of Thoracic Surgeons Predicted Risk of Mortality (PROM) was
      calculated by a formula based on 30 preoperative risk factors. It was used in
      three ways to compare 30-day operative mortality between patients treated with
      OPCAB versus CPB. First, patients were divided into quartiles based on their
      PROM, and mortality rates were compared between OPCAB and CPB patients within
      each PROM quartile. Second, a logistic regression model tested for an interaction
      between surgery type and PROM; a significant interaction would indicate that the
      relative mortality risk of OPCAB versus CPB varied with different PROM levels.
      Finally, locally smoothed kernel regression curves were used to visually estimate
      a threshold PROM point at which mortality rates diverge for the surgery types.
      RESULTS: There were 14,766 consecutive patients, 7,083 OPCAB (48.0%) and 7,683
      CPB (52.0%). There was no difference in operative mortality between OPCAB and CPB
      for patients in the lower two risk quartiles. In the higher risk quartiles there
      was a mortality benefit for OPCAB (odds ratio, 0.62 and 0.45 for OPCAB in the
      third and fourth risk quartiles). Logistic regression analysis confirmed a
      significant interaction between surgery type and PROM (p = 0.005) meaning that
      OPCAB is especially beneficial to patients with higher PROM. This benefit is most
      significant for patients with PROM values above 2.5% to 3%, where mortality
      curves sharply diverge. CONCLUSIONS: Off-pump coronary artery bypass grafting is
      associated with lower operative mortality than coronary artery bypass grafting on
      CPB for higher risk patients. This mortality benefit increases with increasing
      PROM.

PMID- 19766799
TI  - Increased rehospitalization rate after coronary bypass operation for acute
      coronary syndrome: a prospective study in 200 patients.
AB  - BACKGROUND: Patients with acute coronary syndrome (ACS) run increased risk of
      cardiac death or myocardial infarction after coronary artery bypass grafting
      (CABG). Long-term survival is similar in ACS patients and patients with stable
      angina pectoris. This study analyzed the cardiac rehospitalization rate up to 10
      years after CABG for ACS and stable angina. METHODS: CABG was done in 200
      patients, 100 with ACS and 100 with stable angina. Troponin-T levels were assayed
      and the severity of the unstable symptoms was classified according to Braunwald.
      Early outcome, long-term survival, and freedom from cardiac rehospitalization
      were analyzed. RESULTS: Three ACS patients died early and 12 died late. In the
      control group, there were no early and 19 late deaths. The cumulative long-term
      survival was 85% for the ACS patients and 81% for the stable patients (p = 0.75).
      Postoperative myocardial infarction occurred in 5 unstable patients and 1 stable
      patient (p = 0.01). At 3 years after the operation, freedom from cardiac
      rehospitalization was significantly higher in the stable patients (9 vs 27, p =
      0.001). In the end of the follow-up, there were no differences in the
      rehospitalization rate. CONCLUSIONS: Similar and excellent long-term survival was
      found in both ACS and stable patients long-term after CABG. In patients with ACS,
      variables such as elevated troponin-T and angina at rest herald an increased risk
      of perioperative myocardial infarction. Freedom from cardiac rehospitalization is
      significantly higher in stable patients compared with ACS patients during the
      first postoperative years, indicating recurrent ischemia.

PMID- 19766800
TI  - Impact of 24-hour in-house intensivists on a dedicated cardiac surgery intensive
      care unit.
AB  - BACKGROUND: Intensive care unit (ICU) physician staffing models for cardiac
      surgery patients vary widely and correlate poorly with outcomes. Clinical
      outcomes associated with 24-hour, in-house intensivists working in a dedicated
      post-cardiac surgical unit has not been previously investigated. We sought to
      examine the safety and efficacy of such a model. METHODS: A retrospective,
      propensity-matched, cohort study of all patients undergoing a cardiac surgical
      procedure at a single tertiary center was performed. The control cohort (n =
      1,467) consisted of patients admitted to the traditional, mixed surgical
      intensive care unit (SICU) from January 2005 to January 2007. The intervention
      cohort (n = 1,089) consisted of patients admitted to a newly created "hybrid"
      cardiac surgery ICU (CICU) from January 2007 to January 2008, which was staffed
      by 24-hour in-house consultant intensivists and a daytime, fast track cardiac
      anesthesiologist. The primary outcomes were blood product utilization,
      requirement for ventilation, and ICU recidivism. RESULTS: The proportion of
      patients in the CICU cohort who received transfused red blood cells was decreased
      compared with the SICU cohort (30.2% versus 42.3%, p < 0.001). Similar reductions
      in platelets and fresh frozen plasma were also observed. The CICU patients were
      less likely to arrive to the ICU intubated (43.7% versus 66.5%, p < 0.001). There
      were no differences in postoperative complications. Overall hospital length of
      stay was reduced in the CICU cohort by a median of 1 day (6 days [interquartile
      range, 5 to 8] versus 7 days [5 to 9], p < 0.001). Significant reductions in
      mortality and ICU recidivism were not observed. CONCLUSIONS: The current Manitoba
      CICU model of 24-hour intensive care physician/cardiac anesthesiologist staffing
      in postoperative cardiac surgery care is associated with reduced transfusion of
      blood components, decreased requirement for mechanical ventilation, and shorter
      hospital length of stay.

PMID- 19766801
TI  - Incidence and patterns of adverse event onset during the first 60 days after
      ventricular assist device implantation.
AB  - BACKGROUND: Although ventricular assist devices (VADs) provide effective
      treatment for end-stage heart failure, VAD support remains associated with
      significant risk for adverse events (AEs). To date there has been no detailed
      assessment of the incidence of a full range of AEs using standardized event
      definitions. We sought to characterize the frequency and timing of AE onset
      during the first 60 days of VAD support, a period during which clinical
      observation suggests the risk of incident AEs is high. METHODS: A retrospective
      analysis was performed utilizing prospectively collected data from a single-site
      clinical database including 195 patients aged 18 or greater receiving VADs
      between 1996 and 2006. Adverse events were coded using standardized criteria.
      Cumulative incidence rates were determined, controlling for competing risks
      (death, transplantation, recovery-wean). RESULTS: During the first 60 days after
      implantation, the most common AEs were bleeding, infection, and arrhythmias
      (cumulative incidence rates, 36% to 48%), followed by tamponade, respiratory
      events, reoperations, and neurologic events (24% to 31%). Other events (eg,
      hemolysis, renal, hepatic events) were less common (rates <15%). Some events (eg,
      bleeding, arrhythmias) showed steep onset rates early after implantation. Others
      (eg, infections, neurologic events) had gradual onsets during the 60-day period.
      Incidence of most events did not vary by implant era (1996 to 2000 vs 2001 to
      2006) or by left ventricular versus biventricular support. CONCLUSIONS:
      Understanding differential temporal patterns of AE onset will allow preventive
      strategies to be targeted to the time periods when specific AE risks are
      greatest. The AE incidence rates provide benchmarks against which future studies
      of VAD-related risks may be compared.

PMID- 19766802
TI  - Activation of endothelial and coagulation systems in left ventricular assist
      device recipients.
AB  - BACKGROUND: The paucity of organ donors has necessitated redirecting research
      toward finding alternative means to a heart transplant, such as left ventricular
      assist devices (LVADs) that will serve not merely as bridge-to-transplant but
      also as destination therapy. To better understand hemorrhagic and thromboembolic
      complications that currently limit the use of such devices, we studied the
      endothelial and coagulation system changes in LVAD recipients with time. METHODS:
      We studied these markers of endothelial dysfunction: circulating endothelial
      cells and expression of E-selectin, vascular cell adhesion molecule,
      intercellular adhesion molecule, and tissue factor on circulating endothelial
      cells, thrombin generation (prothrombin fragments 1,2 and thrombin/antithrombin),
      and fibrinolysis (D-dimer). Our study group consisted of 21 LVAD recipients (on
      day 0 and on postoperative days 1, 7, 30, 90, and 180) and 7 control patients
      undergoing non-LVAD cardiac surgery. RESULTS: Baseline values of intercellular
      adhesion molecule, E-selectin, tissue factor, thrombin/antithrombin, and D-dimer
      were significantly higher in LVAD recipients than the normal range. Markers of
      thrombin generation (thrombin/antithrombin and prothrombin fragments 1,2) and
      fibrinolysis (D-dimer) peaked postoperatively and declined to baseline levels or
      below by 3 months. But the expression of inducible endothelial markers
      (intercellular adhesion molecule, E-selectin, tissue factor) on circulating
      endothelial cells increased postoperatively, then decreased but remained elevated
      above preoperative levels for up to 6 months. In our control patients, baseline
      levels of intercellular adhesion molecule, E-selectin, tissue factor, D-dimer,
      and thrombin/antithrombin were lower and decreased significantly by day 7, as
      compared with LVAD recipients (p < 0.05). CONCLUSIONS: Left ventricular assist
      device recipients experienced significant baseline activation of endothelial and
      coagulation systems, further accentuated in the early postoperative period. Left
      ventricular assist device recipients also had prolonged activation of the
      endothelial and coagulation systems, suggesting activation of the extrinsic
      (tissue factor) pathway of thrombosis mediated by sustained endothelial
      dysfunction in these patients. Further studies are needed to determine the
      clinical influence of such changes in LVAD recipients.

PMID- 19766803
TI  - A decade of minimally invasive mitral repair: long-term outcomes.
AB  - BACKGROUND: Short-term results with minimally invasive approaches for mitral
      valve repair in degenerative disease have been encouraging, with potential for
      diminishing blood loss and hospital length of stay. Little is known, however,
      about the long-term efficacy of this approach. This report analyzes a single
      institution's results over 12 years with minimally invasive mitral repair.
      METHODS: Since 1986, 3,057 patients have undergone mitral valve repair; 1,601
      patients had degenerative disease and are the subject of this report. Minimally
      invasive mitral repair was done in 1071 patients with a right anterior
      minithoracotomy and direct vision. Clinical and echocardiographic variables were
      entered prospectively into a database. RESULTS: Hospital mortality was 2.2% for
      all patients (36 of 1601); 1.3% for isolated minimally invasive (9 of 712) and
      1.3% (3 of 223) for isolated sternotomy mitral valve repair; and 3.6% (24 of 666)
      for valve repair plus a concomitant cardiac procedure. For isolated valve repair,
      8-year freedom from reoperation was 91% +/- 2% for sternotomy and 95% +/- 1% for
      minimally invasive (p = 0.24), and 8-year freedom from reoperation or severe
      recurrent insufficiency was 90% +/- 2% for sternotomy and 93% +/- 1% for
      minimally invasive (p = 0.30). Eight-year freedom from all valve-related
      complications was 86% +/- 3% for sternotomy and 90% +/- 2% for minimally invasive
      (p = 0.14). CONCLUSIONS: These data indicate that long-term outcomes after
      minimally invasive mitral repair are excellent and equivalent to results achieved
      with sternotomy. In view of previously published advantages of short-term
      morbidity, minimally invasive approaches to mitral valve surgery deserve expanded
      use.

PMID- 19766804
TI  - Thoracoscopic versus open mitral valve repair: a propensity score analysis of
      early outcomes.
AB  - BACKGROUND: The very low risk of mitral valve repair performed through median
      sternotomy must be reproducible when using a port-access approach to justify
      early repair employing minimally invasive platforms. We compared the outcomes of
      mitral valve repair performed through port access using thoracoscopic assistance
      (port) versus median sternotomy (open). METHODS: The early results after mitral
      valve repair performed by two different surgeons at two separate institutions
      were analyzed. Between January 1999 and December 2006, isolated mitral valve
      repair was performed with a port approach in 350 patients and an open approach in
      365 patients. RESULTS: The mean age was similar between the two groups; however,
      port patients were more frequently female (148 [42%] versus 119 [33%], p =
      0.007), and had a higher likelihood of having New York Heart Association class
      III to IV symptoms (100 [29%] versus 48 [13%], p < 0.001), diabetes mellitus (19
      [5%] versus 8 [2%], p = 0.023), congestive heart failure (90 [26%] versus 26
      [7%], p < 0.001), and a lower ejection fraction (53% versus 64%, p < 0.001)
      preoperatively. Cross-clamp time (104 versus 24 minutes, p < 0.001) and bypass
      time (140 versus 33 minutes, p = 0.001) were significantly lower for the open
      group. On univariate analysis, the duration of postoperative ventilatory support
      was significantly lower in the port group (5.0 versus 11.0 hours, p < 0.001);
      however, the length of hospital stay was longer (6.95 versus 6.19 days, p <
      0.001). There were 2 early deaths (2 port versus 0 open). A propensity score
      factor was calculated and utilized to account for differences between groups.
      After adjusting for propensity score and significant factors identified in
      multivariate models, port mitral repair independently predicted a diminished
      duration of postoperative ventilatory support (p = 0.045), but there were no
      significant differences in other outcomes including postoperative blood
      transfusion, reoperation for hemorrhage, or length of stay in hospital.
      CONCLUSIONS: Despite longer cross-clamp and bypass times, early outcomes using a
      thoracoscopic port-access approach were similar to those for mitral valve repair
      performed through median sternotomy. Minimally invasive mitral valve repair was
      associated with a shorter time to extubation, but that did not translate into a
      diminished duration of postoperative hospitalization.

PMID- 19766805
TI  - Invited commentary.

PMID- 19766806
TI  - Nonresectional repair of the barlow mitral valve: importance of dynamic annular
      evaluation.
AB  - BACKGROUND: The most extensive form of myxomatous degeneration of the mitral
      valve causing severe mitral regurgitation is "Barlow disease." Surgical repair of
      this condition has been considered difficult because of the extent and magnitude
      of annular, leaflet, and chordal abnormalities and has usually involved partial
      resection of one or both mitral leaflets. METHODS: A surgical approach has been
      developed which does not involve leaflet resection. Instead, by means of precise
      dynamic annular sizing, a predetermined zone of leaflet apposition is achieved.
      The leaflets are positioned so that their large area is contained within the left
      ventricle. Normal annular, leaflet, and papillary muscle dynamic function is
      restored. RESULTS: This procedure was performed in 61 patients. The repair rate
      was 100%. The mean age was 57.6 +/- 12.7 years. They were 67.2% male. The
      preoperative anteroposterior annular dimension was 52.1 +/- 4.3 mm. The full,
      flexible complete ring size was 33.4 +/- 1.9 mm. There was no perioperative
      mortality. There was no systolic anterior leaflet motion. All patients were
      discharged with no or mild mitral regurgitation. At a follow-up interval of 1.2
      +/- 2.1 years one patient had developed recurrent mitral regurgitation, secondary
      to marked remodeling to normal left ventricular function. CONCLUSIONS: Initial
      experience with a nonresectional approach for Barlow disease has produced good
      early results.

PMID- 19766807
TI  - Mitral gradients and frequency of recurrence of mitral regurgitation after ring
      annuloplasty for ischemic mitral regurgitation.
AB  - BACKGROUND: Undersized ring annuloplasty and surgical revascularization are
      commonly used to correct ischemic mitral regurgitation (MR), but published series
      have failed to demonstrate a benefit compared with revascularization alone. We
      hypothesized that surgical revascularization and annuloplasty lead to a durable
      repair, but may also lead to increased mitral gradients that could limit the
      benefit of the repair technique. METHODS: Data were collected for 222 consecutive
      patients who underwent combined revascularization and repair for ischemic MR
      between 1999 and 2006. The most recent transthoracic echocardiogram available for
      each patient (namely, the study that occurred at the latest date after surgery)
      was reviewed to define the fate of ischemic MR. When present, the mean gradient
      across the mitral valve was measured. Cox regression modeling was then performed
      to determine whether increasing gradients were associated with decreased long
      term survival or increased hospitalization for heart failure. RESULTS: For the
      group of 222 patients, echocardiographic follow-up was available for 68% (149
      patients). At follow-up, 1.3% had severe MR and 9.4% had moderate MR; 54% of
      patients (66 of 123) were found to have gradients of 5 mm or greater across the
      mitral valve, with 11% demonstrating gradients of 8 mm or more. Cox proportional
      hazards models failed to show adverse effects of increasing mitral gradient on
      outcomes analyzed: survival hazard ratio = 0.95 (95% confidence interval: 0.82 to
      1.11, p = 0.527) and survival/heart failure hospitalization hazard ratio = 1.04
      (95% confidence interval: 0.93 to 1.17, p = 0.488). CONCLUSIONS: Undersized ring
      annuloplasty and revascularization can provide a durable correction of ischemic
      mitral regurgitation. This technique frequently increases the gradient across the
      mitral valve, but increasing mitral gradient does not appear to adversely impact
      survival or heart failure hospitalization.

PMID- 19766808
TI  - Is the anterior intertrigonal distance increased in patients with mitral
      regurgitation due to leaflet prolapse?
AB  - BACKGROUND: Severe mitral regurgitation (MR) leads to progressive enlargement of
      left ventricular dimensions and, consequently, the mitral valve (MV) annulus.
      Data from animal and cadaver studies suggest that the mitral annulus may dilate
      asymmetrically in certain conditions, which may influence the choice of valve
      repair technique. Although it is generally accepted that the posterior mitral
      annulus dilates in patients with severe MR due to leaflet prolapse, the stability
      of the anterior intertrigonal distance has not yet been demonstrated in humans.
      METHODS: We obtained real-time, three-dimensional (3D) transesophageal
      echocardiographic images of the MV in 44 patients: 29 patients scheduled to
      undergo MV repair for severe MR due to leaflet prolapse (MV disease group) and 15
      normal outpatients undergoing evaluation for various reasons (control group).
      Mitral valve repair was performed by median sternotomy or minimally invasively
      using thoracoscopic or robotic assistance. All patients underwent implantation of
      a standard-length flexible 63-mm posterior annuloplasty band at the time of
      mitral repair and we obtained postoperative 3D images for 11 patients after
      separation from bypass. Mitral annular dimensions were measured throughout the
      cardiac cycle using reconstructive analysis software (QLAB MVQ Version 6.0;
      Phillips, Bothell, WA). RESULTS: The mean patient age was 60 years; 30 were men.
      The mean ejection fraction was 0.61 and was similar between the two groups (p =
      0.16). In patients with MR due to leaflet prolapse, posterior annular length and
      total annular circumference were significantly larger than in control patients (p
      < 0.001). In contrast, there was no detectable difference in the anterior
      intertrigonal distance between patients with MR and normal controls. After mitral
      valve leaflet repair and posterior annuloplasty there was a significant decrease
      in both the total annular circumference and posterior annular length (p < 0.0001)
      while cyclic annular contraction was preserved. CONCLUSIONS: Although the
      posterior mitral annulus is enlarged in patients with significant MR due to
      degenerative leaflet prolapse, there is no evidence that the intertrigonal
      distance is abnormal in these patients. Our data support the conclusion that
      posterior annular reduction with a flexible device at the time of mitral valve
      repair is important, and that altering the anterior intertrigonal portion of the
      mitral annulus is unnecessary.

PMID- 19766809
TI  - Clinical and echocardiographic impact of functional tricuspid regurgitation
      repair at the time of mitral valve replacement.
AB  - BACKGROUND: The indications for tricuspid valve repair in the setting of mitral
      valve disease and concomitant tricuspid regurgitation (TR) remain unclear. We
      examined patients undergoing mitral valve replacement (MVR) to determine the
      effect of TR and tricuspid valve repair on survival, functional status, and
      postoperative TR. METHODS: Between 1990 and 2005, 624 patients underwent MVR.
      Data included detailed serial echocardiographic tricuspid valve measurements,
      functional status, and survival data. Preoperative TR exceeded 2+ in 231: 125
      received tricuspid repair and MVR, whereas 106 received MVR alone. Clinical and
      echocardiographic follow-up were complete (average, 6.8 +/- 4.8 years).
      Parametric and semi-parametric tests were used to analyze outcomes. RESULTS: TR
      exceeding 2+ at operation was associated with a 53% increase in late death (p =
      0.003). Tricuspid repair prevented echocardiographic progression of TR and
      improved congestive heart failure symptoms (both p < 0.01). Overall survival did
      not improve (p = 0.3). A trend to worsening TR in patients was noted with a
      larger tricuspid annulus diameter and without significant (<or= 1+) TR
      preoperatively (odds ratio, 1.4 per cm increase in annulus diameter; p = 0.5),
      but this was not associated with worse functional or vital outcomes. CONCLUSIONS:
      In patients undergoing MVR, tricuspid repair is indicated when TR exceeds 2+ to
      alleviate heart failure symptoms, but without significantly improving survival in
      this population. TR of 2+ or less may not require repair. Echocardiographic
      tricuspid annular dimensions alone, in the absence of significant (<or= 1+) TR
      preoperatively, should not dictate the performance of tricuspid repair.

PMID- 19766810
TI  - Early and midterm outcomes for tricuspid valve surgery after left-sided valve
      surgery.
AB  - BACKGROUND: The purpose of this study was to compare the early and midterm
      results of tricuspid valve replacement (TVR) versus tricuspid valve repair (TVr)
      for late tricuspid regurgitation after left-sided valve surgery. METHODS: Fifty
      one consecutive patients who underwent tricuspid valve surgery after left-sided
      valve surgery between January 1995 and April 2008 were included. Thirty-seven
      patients underwent TVR, and 14 patients underwent TVr. Tricuspid valve
      replacement was performed along with concomitant procedures in 27 patients
      (73.0%). Patients undergoing TVR were more likely to have severe tricuspid
      regurgitation (64.3% versus 89.2%; p = 0.037), or a previous history of tricuspid
      regurgitation repair (7.1% versus 51.4%; p = 0.004). RESULTS: There was no
      hospital death in both TVr and TVR groups. However, in comparison to TVr
      patients, TVR patients needed a greater amount of hemofiltration (59 +/- 23
      versus 80 +/- 36; p = 0.026) and had longer periods of hospital stays (13.5 +/-
      4.4 versus 26.9 +/- 25.7 days; p = 0.049). Survival rates at 1, 5, and 10 years
      were 97%, 93%, and 63% for patients undergoing TVR, and 93%, 93%, and 81% for
      patients undergoing TVr, respectively. There was no statistical difference in
      midterm survival rates between the two groups. Cox regression analysis revealed
      that left ventricular ejection fraction of 0.40 or less (p = 0.034) and age (p =
      0.035) were independent predictors of late mortality after TVR or TVr.
      CONCLUSIONS: Patients undergoing TVR had a more advanced preoperative tricuspid
      regurgitation grade and significantly prolonged hospital stays. However, there
      were no statistical differences in early and midterm outcomes between the two
      groups.

PMID- 19766811
TI  - Management of mild aortic stenosis at the time of coronary artery bypass surgery:
      should the valve be replaced?
AB  - BACKGROUND: General consensus favors aortic valve replacement (AVR) for patients
      with moderate aortic stenosis (AS) undergoing coronary artery bypass graft
      surgery (CABG); however, the management of similar patients with mild AS is
      controversial. We therefore investigated such patients to determine incremental
      risk of concomitant AVR, progression of AS among those undergoing CABG alone, and
      operative risk of AVR after prior CABG. METHODS: Between January 1993 and
      December 2003, 316 consecutive patients with mild AS (mean gradient >15, <30 mm
      Hg) underwent CABG only (107) or CABG plus AVR (209). Follow-up was obtained by
      review of the medical record, the Social Security Death Index, and postal
      questionnaire. RESULTS: The operative mortality was 3.7% for CABG only and 4.3%
      for CABG plus AVR (p = 1). Survival at a mean of 5.4 +/- 3.6 years was similar.
      Multivariate predictors of late mortality included comorbid illnesses (Charlson
      comorbidity score and age-weighted summary of diseases; p = 0.001), small body
      surface area (p = 0.001), low ejection fraction (p = 0.007), preoperative
      permanent pacemaker (p = 0.04), and congestive heart failure (p = 0.046), but not
      AVR. Twenty-three CABG-only patients (21%) underwent subsequent AVR (mean 5.6 +/-
      1.8 years) without mortality. Aortic valve replacement at the time of initial
      CABG (p <0.001) and older age (p = 0.02) were multivariate predictors of freedom
      from reoperation. CONCLUSIONS: Prophylactic AVR for mild AS at CABG does not
      confer a survival benefit, and the likelihood of requiring AVR after CABG alone
      is low in the first 5 years. The decision to intervene on the valve is critically
      dependent upon the incremental operative risk imposed by concomitant AVR and late
      survival.

PMID- 19766812
TI  - Left ventricular mass regression after porcine versus bovine aortic valve
      replacement: a randomized comparison.
AB  - BACKGROUND: It is unclear whether small differences in transprosthetic gradient
      between porcine and bovine biologic aortic valves translate into improved
      regression of left ventricular (LV) hypertrophy after aortic valve replacement.
      We investigated transprosthetic gradient, aortic valve orifice area, and LV mass
      in patients randomized to aortic valve replacement with either the Medtronic
      Mosaic (MM) porcine or an Edwards Perimount (EP) bovine pericardial
      bioprosthesis. METHODS: One hundred fifty-two patients with aortic valve disease
      were randomly assigned to receive either the MM (n = 76) or an EP prosthesis.
      There were 89 men (59%), and the mean age was 76 years. Echocardiograms from
      preoperative, postoperative, predismissal, and 1-year time points were analyzed.
      RESULTS: Baseline characteristics and preoperative echocardiograms were similar
      between the two groups. The median implant size was 23 mm for both. There were no
      early deaths, and 10 patients (7%) died after dismissal. One hundred seven of 137
      patients (78%) had a 1-year echocardiogram, and none required aortic valve
      reoperation. The mean aortic valve gradient at dismissal was 19.4 mm Hg (MM)
      versus13.5 mm Hg (EP; p < 0.0001), and at 1 year was 20.4 mm Hg versus 13.4 mm Hg
      (p < 0.0001). These differences were similar when the analysis was stratified by
      surgically measured annular size. The mean change in aortic valve gradient
      between predismissal and 1-year echocardiogram was +2.2 mm Hg (p = 0.02) for MM
      and -0.8 mm Hg (p = 0.33) for EP patients (p = 0.01 MM versus EP). The mean
      indexed aortic valve orifice area for MM and EP groups at dismissal and at 1 year
      was 0.9 cm(2)/m(2) versus 1.1 cm(2)/m(2), respectively (p < 0.01; p < 0.0001).
      During the first year after implantation, both groups demonstrated similar
      regression of LV mass index (MM, -32.4 g/m(2) versus EP, -27.0 g/m(2); p = 0.40).
      Greater preoperative LV mass index was the sole independent predictor of greater
      LV mass regression after surgery (p < 0.01). CONCLUSIONS: Small differences in
      transprosthetic gradient and indexed aortic valve orifice area exist between
      porcine and bovine aortic valves. Despite this, both prostheses allow similar
      regression of LV mass during the first year after aortic valve replacement.

PMID- 19766813
TI  - Adjustment of sinotubular junction for aortic insufficiency secondary to
      ascending aortic aneurysm.
AB  - BACKGROUND: Dilatation of the sinotubular junction (STJ) causes aortic
      regurgitation (AR) in patients with ascending aneurysm. These patients can regain
      valve competence by simple reduction of the diameter of STJ. Results of this
      technique were investigated clinically and echocardiographically. METHODS:
      Replacement of the ascending aorta with reduction of the diameter of the STJ to
      correct AR (mean grade, 2.7 +/- 0.7) was performed in 29 consecutive patients
      (mean age, 73.2 +/- 6.2). Two required repair of cusp prolapse. All underwent
      ascending aortic aneurysm replacement. Echocardiographic studies were performed
      at discharge and during latest clinical follow-up (mean follow-up, 3.8 +/- 2.5
      years). RESULTS: No hospital deaths occurred. The AR grade at discharge was 0.7
      +/- 0.5. No valve related-deaths occurred. Actual survival at 8 years was 91% +/-
      9%. Failure occurred 4.1 years postoperatively in a patient with bicuspid valve.
      Three patients had late recurrence of AR that was caused by aortic root
      dilatation in bicuspid valves in 2. Multivariate analysis showed bicuspid aortic
      valve was the predictor of late progression of AR. The freedom from more than
      grade II AR at 8 years was 79.5% +/- 10.7%. CONCLUSIONS: Adjustment of the
      diameter of STJ could treat AR secondary to ascending aortic aneurysm with nearly
      normal aortic cusps. Midterm results of this procedure were acceptable. Although
      bicuspid aortic valve is the risk factor for late AR due to dilation of remaining
      aortic root, this procedure provides satisfactory long-term outcomes among the
      patients with tricuspid valve.

PMID- 19766814
TI  - Long-term results after repair of type a acute aortic dissection according to
      false lumen patency.
AB  - BACKGROUND: Late survival and freedom from retreatment on the descending aorta
      was evaluated after ascending aortic repair for type A acute aortic dissection
      (TAAAD). METHODS: Between March 1992 and January 2006, 189 TAAAD patients (mean
      age, 52 +/- 11; range, 17 to 83 years) were included; of these, 58 had a patent
      false lumen, and 49 had Marfan syndrome. The descending aorta was evaluated
      postoperatively with computed tomography (CT). Late outcomes were assessed by Cox
      regression analysis and actuarial survival and freedom from retreatment by the
      Kaplan-Meier method. Mean follow-up was 88 +/- 44 months. RESULTS: There were 38
      (20%) late deaths. At 10 years, survival was 89.8% +/- 2.1% for patients with an
      occluded false lumen and 59.8% +/- 3.5% for patients with a patent false lumen (p
      = 0.001), and freedom from retreatment on the descending aorta was 94.2% +/- 3.1%
      for an occluded false lumen and 63.7% +/- 2.6% for a patent false lumen (p <
      0.0001). Descending aortic rupture (p = 0.002) and a patent false lumen (p =
      0.001) were predictors for late death. Patent false lumen (p = 0.0001), Marfan
      syndrome (p = 0.03), and descending aortic diameter 4.5 cm or larger (p = 0.002)
      were predictors for retreatment. CONCLUSIONS: A patent false lumen was a
      predictor for late death and retreatment on the descending aorta. Marfan syndrome
      and aortic size exceeding 4.5 cm were predictors for late retreatment. These
      patients require very close follow-up and a plan for retreatment on the
      descending aorta to prevent sudden rupture and late death.

PMID- 19766815
TI  - Invited commentary.

PMID- 19766816
TI  - Growth rate of affected aorta in patients with type B partially closed aortic
      dissection.
AB  - BACKGROUND: Our purpose was to evaluate the growth rate (GR) of the affected
      aorta and to clarify whether a partially closed false lumen can affect aortic
      enlargement in patients with type B double-barrelled aortic dissection (AD).
      METHODS: Seventy-one patients (mean age, 64.4 years) who had experienced AD were
      enrolled in this study. Regular follow-up computed tomography studies (mean, 48.9
      months) were performed. During the follow-up period, aortic diameter was measured
      with computed tomography. The fastest GR was calculated. RESULTS: Based on final
      computed tomography findings, the patients were divided into three groups: those
      with completely closed false lumens (n = 8), those with partially closed false
      lumens (n = 20), and those with patent false lumens (n = 43). Among the patients
      with partially closed false lumens, 3 of 20 (15%) had a sac formation type and 17
      (85%) had a non-sac formation type. The mean fastest GRs for groups with a
      completely closed false lumen, partially closed false lumen, and patent false
      lumen were -0.2 +/- 0.6, 4.0 +/- 4.3, and 4.9 +/- 4.5 mm/year, respectively. The
      differences among the three groups were statistically significant (p = 0.0149).
      In the partially closed false lumen group, the mean fastest GRs of the sac and
      non-sac formation types were 12.7 +/- 1.1 and 2.6 +/- 2.7 mm/year, respectively;
      this difference is statistically significant (p = 0.007). CONCLUSIONS: Affected
      aortas with partially closed false lumens do not exhibit the highest GR. The
      status of a partially closed false lumen is not a significant risk factor for
      enlargement; however, careful follow-up study is needed whenever the sac
      formation type of partially closed false lumen is identified.

PMID- 19766817
TI  - Invited commentary.

PMID- 19766818
TI  - Early outcome of endovascular treatment of acute traumatic aortic injuries: the
      talent thoracic retrospective registry.
AB  - BACKGROUND: Acute traumatic injury of the thoracic aorta (TAI) is a life
      threatening complication in patients who sustain deceleration or crush injuries.
      This study was conducted to examine the results in patients who underwent
      endovascular repair with the Talent (Medtronic/AVE, Santa Rosa, CA) thoracic
      stent graft for acute traumatic injury. METHODS: Out of 457 consecutive endograft
      patients, 41 (9%) were treated for traumatic aortic conditions. There were 36
      males with a mean age of 36 +/- 14 years. Mean aortic diameter at the time of
      intervention was 34 mm +/- 9 (range, 20 to 70 mm). The mean length of covered
      aorta was 106 mm (range, 5 to 130 mm) with only one stent graft used in 98% (40)
      of all cases. Median follow-up period for hospital survivors was 13 months (1.0
      to 69.0 months). RESULTS: Stent graft implantation was technically successful in
      all cases (100%). One patient died during hospitalization, yielding an overall in
      hospital mortality rate of 2.4%. Procedural-related paraplegia was zero and a
      primary endoleak was observed in 1 patient. Postoperative complications occurred
      in 4 patients (3 respiratory failures, 1 multiorgan failure). No patient required
      conversion to open surgical repair. CONCLUSIONS: The treatment of acute traumatic
      injuries of the descending thoracic aorta with the Talent stent graft is a
      feasible and safe technique; it provides low morbidity and mortality rates in the
      early postoperative period, and early results are encouraging. However, long-term
      studies are worthwhile to evaluate the effectiveness and the durability of this
      procedure.

PMID- 19766819
TI  - Cardiac operations in the presence of meningioma.
AB  - BACKGROUND: We investigated the effect of concomitant intracranial meningiomas on
      perioperative and postoperative complications after cardiac operations. Also
      studied was the intraoperative and perioperative management and long-term outcome
      of such patients. METHODS: We retrospectively evaluated 16 cardiac surgical
      patients with intracranial meningiomas between January 1996 and July 2007.
      Neurologic outcome, incidence of transient neurologic deficits, and long-term
      follow-up focusing on freedom from any cardiac or neurosurgical intervention were
      assessed. RESULTS: Five men and 11 women with a concomitant diagnosis of
      intracranial meningioma underwent cardiac operations using extracorporeal
      circulation. One patient received additional edema prophylaxis by intravenous
      dexamethasone. All patients were discharged home in good physical condition. Data
      on long-term survival were available on 14 patients, with 12 alive.
      Postoperatively, 2 patients died from myocardial infarction at 26.8 months and 2
      from metastatic colon cancer at 57.9 months. Perioperative neurologic disorders
      were observed in 2 patients, comprising one stroke after intervention for aortic
      dissection and one thromboembolic event 2 weeks after biologic mitral valve
      replacement due to anticoagulation disorders. No meningioma-related adverse event
      was observed. CONCLUSIONS: The presence of intracranial meningioma does not
      appear to be a risk factor for patients undergoing cardiac operations. No
      meningioma-related neurologic sequelae were documented postoperatively.
      Neurosurgical consultation should be obtained in all patients preoperatively.

PMID- 19766820
TI  - Newly developed tissue-engineered material for reconstruction of vascular wall
      without cell seeding.
AB  - BACKGROUND: We have developed a tissue-engineered patch for cardiovascular
      repair. Tissue-engineered patches facilitated site-specific in situ
      recellularization and required no pretreatment with cell seeding. This study
      evaluated the patches implanted into canine pulmonary arteries. METHODS: Tissue
      engineered patches are biodegradable sheets woven with double-layer fibers. The
      fiber is composed of polyglycolic acid and poly-L-lactic acid, and compounding
      collagen microsponges. The patches (20- x 25-mm) were implanted into the canine
      pulmonary arterial trunks. At 1, 2, and 6 months after implantation (n = 4), they
      were explanted and characterized by histologic and biochemical analyses.
      Commercially available patches served as the control. No anticoagulant therapy
      was administered postoperatively. RESULTS: No aneurysm or thrombus was present
      within the patch area in all groups. The remodeled tissue predominantly consisted
      of elastic and collagen fibers, and the endoluminal surface was covered with a
      monolayer of endothelial cells and multilayers of smooth muscle cells beneath the
      endothelial layer. The elastic and collagen fibers and smooth muscle cells kept
      increasing with a maximum at 6 months, while a monolayer of endothelial cells was
      preserved. The expression levels of messenger RNA of several growth factors in
      the tissue-engineered patches were higher than those of native tissue at 1 and 2
      months and decreased to normal level at 6 months. No regenerated tissue was found
      on the endoluminal surface in the control group. CONCLUSIONS: The novel tissue
      engineered patches showed in situ repopulation of host cells without prior ex
      vivo cell seeding. This is promising material for repair of the cardiovascular
      system.

PMID- 19766821
TI  - Cardiopulmonary effects of continuous negative pressure wound therapy in swine.
AB  - BACKGROUND: Negative pressure wound therapy (NPWT) has been used for complex
      sternotomy wounds. Some reports describe foam placement below the posterior
      sternal table. We compared the hemodynamic and pulmonary effects of foam location
      during NPWT after median sternotomy. METHODS: Swine were randomized into four
      groups (n = 6 per group). A polyurethane open cell foam dressing was placed
      either within or below the sternal table. In one-half, a silicone mesh barrier
      was placed between the heart and the foam. The NPWT was applied at -125 mm Hg and
      then released to ambient pressure. This cycle was repeated two more times, and
      the foam was removed. Heart rate, mean arterial pressure, cardiac output, mixed
      venous oxygenation, central venous pressure, and pulmonary artery wedge pressure
      were measured. Peak inspiratory pressure, mean airway pressure, work of
      breathing, and intrathoracic pressure measurements were recorded. RESULTS:
      Intersternal placement of foam did not affect hemodynamic parameters. Substernal
      placement resulted in depression of hemodynamic variables which improved when
      negative pressure was applied. Pulmonary mechanics were not affected by foam
      location. CONCLUSIONS: Initial placement of the foam dressing below the posterior
      sternal table caused reversible depression of cardiac function which appears to
      be consistent with direct cardiac compression. NPWT therapy had no clinically
      significant impact on pulmonary parameters. The use of a protective barrier does
      not alter hemodynamic or pulmonary parameters but continues to be recommended
      when NPWT is used for sternotomy wounds.

PMID- 19766822
TI  - Morbidity and mortality risk factors in adults with congenital heart disease
      undergoing cardiac reoperations.
AB  - BACKGROUND: Reoperations represent relatively frequent events in adults with
      congenital heart disease (ACHD). Cardiac operations in these patients present
      major difficulties in management and technique. Although reoperations in ACHD are
      becoming increasingly frequent, limited knowledge exists regarding perioperative
      risk factors. METHODS: The study included 164 ACHD patients who underwent cardiac
      reoperations between January 2002 and December 2007 at our institution.
      Preoperative and intraoperative data were analyzed to identify morbidity and
      mortality risk factors. RESULTS: Reoperations included pulmonary valve
      implantation or conduit replacement in 60, aortic valve/root procedures in 36,
      residual atrial or ventricular septal defect closure in 19, and Fontan
      operation/conversion in 19. Hospital mortality was 3.6%. The mean mechanical
      ventilation time was 26 hours. Mean intensive care unit stay was 3.1 days. Severe
      postoperative complications occurred in 24 (15.1%). Cardiopulmonary bypass time
      (p = 0.001), Fontan operation/conversion (p = 0.001), preoperative hematocrit (p
      = 0.004), previous number of operations (p = 0.001), and preoperative congestive
      heart failure (p = 0.021) were associated with severe morbidity. No factor was
      associated with death. CONCLUSIONS: Reoperations in ACHD are mostly due to right
      ventricular outflow tract lesions and were associated with a low mortality rate
      if performed in a center with a considerable activity and a dedicated program.
      Severe morbidity is relatively frequent and is generally associated with the
      preoperative (high hematocrit due to cyanosis, congestive heart failure, and the
      number of previous operations) and operative (Fontan operation/conversion and
      cardiopulmonary bypass duration) conditions of the patient.

PMID- 19766823
TI  - Invited commentary.

PMID- 19766824
TI  - Fontan palliation in the modern era: factors impacting mortality and morbidity.
AB  - BACKGROUND: Advances in management of the Fontan patient include interval
      superior cavopulmonary shunt, total cavopulmonary connection, either lateral
      tunnel or extracardiac conduit, and the use of a fenestration. Coincident with
      these improvements, Fontan palliation has been applied to a wider ranger of
      anatomic subgroups. METHODS: A cross-sectional analysis of 256 consecutive
      patients undergoing a total cavopulmonary connection Fontan after superior
      cavopulmonary shunt between January 1, 1994, and June 30, 2007 were studied.
      Fenestration was used selectively. Fontan failure was defined as death,
      transplant, or takedown. Event-free survival was defined as freedom from death,
      transplant, Fontan takedown, functional class III to IV, pacemaker,
      antiarrhythmic medication, protein-losing enteropathy, stroke, or thrombus.
      RESULTS: Survival was 97% +/- 1%, 96% +/- 1%, and 94% +/- 2%, respectively, at 1,
      5, and 10 years. Event-free survival was 96% +/- 1%, 87% +/- 3%, and 64% +/- 6%,
      respectively, at 1, 5, and 10 years. Factors predicting worse event-free survival
      included longer cross-clamp time (p = 0.003), fenestration (p = 0.014), and
      longer hospital length of stay (p = 0.016). Ventricular morphology did not
      predict outcome. Left ventricle (n = 113, 44%) versus right ventricle (n = 142,
      56%) failure-free survival (death, transplant, or Fontan takedown) at 10 years
      was 92% +/- 4% versus 91% +/- 3%, respectively (p = 0.19). Left ventricle versus
      right ventricle event-free survival at 10 years was 75% +/- 7% versus 67% +/- 9%,
      respectively (p > 0.1). CONCLUSIONS: Survival for patients undergoing a
      completion Fontan in the current era is excellent, but patients remain at risk
      for morbid events. In the intermediate follow-up period, we could not identify a
      difference in outcome between dominant left and right ventricle morphology.

PMID- 19766825
TI  - The outflow tract in transposition of the great arteries: an anatomic and
      morphologic study.
AB  - BACKGROUND: Neoaortic root dilatation is observed after the arterial switch
      operation for transposition of the great arteries. Although structural
      differences in the vessel wall of these patients may be of influence, we
      hypothesize that a histomorphologic difference in composition and embedding of
      the fibrous annulus in transposition of the great arteries may play a role in
      neoaortic root dilatation. METHODS: Two normal human hearts and two unoperated
      human hearts with transposition of the great arteries, 1 day postnatal, were
      studied. Histologic sections stained for collagen, myocardium, and elastin were
      prepared, and three-dimensional reconstructions of the outflow tracts were made
      to enable comparison of the morphologic structures between the normal hearts and
      those with transposition of the great arteries. RESULTS: The amount of collagen
      in the arterial roots was diminished in hearts with transposition of the great
      arteries compared with the normal hearts. In addition, the anchorage and
      embedding of both arterial roots in the myocardium was less extensive in
      transposition of the great arteries. The changed position of the arteries in the
      malformed hearts results in less support for the roots from the surrounding
      atrioventricular myocardium. CONCLUSIONS: The combination of the observed
      histomorphologic differences in amount of collagen and myocardial support may be
      an explanation for the neoaortic root dilatation observed after the arterial
      switch operation. The developmental background of the observed deficient fibrous
      annulus formation may originate from an epicardial problem.

PMID- 19766826
TI  - Preoperative extracorporeal membrane oxygenation as a bridge to cardiac surgery
      in children with congenital heart disease.
AB  - BACKGROUND: The efficacy of extracorporeal membrane oxygenation (ECMO) in
      bridging children with unrepaired heart defects to a definitive or palliative
      surgical procedure has been rarely reported. The goal of this study is to report
      our institutional experience with ECMO used to provide preoperative stabilization
      after acute cardiac or respiratory failure in patients with congenital heart
      disease before cardiac surgery. METHODS: A retrospective review of the ECMO
      database at Children's Hospital Boston was undertaken. Children with unrepaired
      congenital heart disease supported with ECMO for acute cardiac or respiratory
      failure as bridge to a definitive or palliative cardiac surgical procedure were
      identified. Data collection included patient demographics, indication for ECMO,
      details regarding ECMO course and complications, and survival to hospital
      discharge. RESULTS: Twenty-six patients (18 male, 8 female) with congenital heart
      disease were bridged to surgical palliation or anatomic repair with ECMO. Median
      age and weight at ECMO cannulation were, respectively, 0.12 months (range, 0 to
      193) and 4 kg (range, 1.8 to 67 kg). Sixteen patients (62%) survived to hospital
      discharge. Variables associated with mortality included inability to decannulate
      from ECMO after surgery (p = 0.02) and longer total duration of ECMO (p = 0.02).
      No difference in outcomes was found between patients with single and
      biventricular anatomy. CONCLUSIONS: Extracorporeal membrane oxygenation, used as
      a bridge to surgery, represents a useful modality to rescue patients with failing
      circulation and unrepaired complex heart defects.

PMID- 19766827
TI  - Evaluation of a shape memory alloy reinforced annuloplasty band for minimally
      invasive mitral valve repair.
AB  - PURPOSE: An in vitro study using explanted porcine hearts was conducted to
      evaluate a novel annuloplasty band, reinforced with a two-phase, shape memory
      alloy, designed specifically for minimally invasive mitral valve repair.
      DESCRIPTION: In its rigid (austenitic) phase, this band provides the same
      mechanical properties as the commercial semi-rigid bands. In its compliant
      (martensitic) phase, this band is flexible enough to be introduced through an 8
      mm trocar and is easily manipulated within the heart. EVALUATION: In its rigid
      phase, the prototype band displayed similar mechanical properties to commercially
      available semi-rigid rings. Dynamic flow testing demonstrated no statistical
      differences in the reduction of mitral valve regurgitation. In its flexible
      phase, the band was easily deployed through an 8-mm trocar, robotically
      manipulated and sutured into place. CONCLUSIONS: Experimental results suggest
      that the shape memory alloy reinforced band could be a viable alternative to
      flexible and semi-rigid bands in minimally invasive mitral valve repair.

PMID- 19766828
TI  - A new vacuum-assisted probe for minimally invasive radiofrequency ablation.
AB  - PURPOSE: The Cobra Adhere XL (Estech, San Ramon, CA) is a multiple-electrode,
      temperature-controlled, monopolar radiofrequency probe with a vacuum-assisted
      stabilization system. We evaluated this new technology for epicardial ablation of
      atrial fibrillation in mitral valve patients through a right mini-thoracotomy.
      DESCRIPTION: Between June and August 2008, 12 patients underwent minimal invasive
      surgery for mitral disease and ablation for atrial fibrillation with the Cobra
      Adhere XL (Estech). Three patients had paroxysmal atrial fibrillation. Off-pump
      pulmonary vein isolation was performed with an epicardial oval lesion parallel to
      the mitral plane. In 10 patients, an endocardial lesion to the mitral annulus was
      added. EVALUATION: There were no operative deaths or major postoperative
      complications. At a mean follow-up of 8.76 +/- 1.0 months, 11 patients (91.67%)
      were in stable sinus rhythm. Echocardiography underscored a complete recovery of
      atrial transport function in most of these patients (90.91%). No major cardiac
      and cerebrovascular events occurred during follow-up. CONCLUSIONS: Left-side
      ablation combined with minimally invasive surgery for mitral disease can be
      easily, safely, and effectively performed with the Cobra Adhere XL probe.

PMID- 19766829
TI  - Transcatheter valve-in-valve aortic valve implantation: 16-month follow-up.
AB  - Off-pump transcatheter, transapical valve-in-valve aortic valve implantation into
      a failed surgically implanted aortic valve was successfully performed in an 85
      year-old man. He was discharged on postoperative day 5, and remained well at his
      16-month follow-up. Echocardiography at 12 months showed normal prosthetic valve
      function without displacement, recoil, or regurgitation. Transcatheter
      transapical valve-in-valve aortic valve implantation is feasible and could be a
      viable approach for selected patients.

PMID- 19766830
TI  - Simultaneous heart and kidney transplantation after bridging with the CardioWest
      total artificial heart.
AB  - End-stage renal failure is often considered a relative contraindication for total
      artificial heart implantation due to the increased risk of mortality after
      transplantation. We report the successful treatment of a patient having heart and
      renal failure with the CardioWest (SynCardia Inc, Tucson, AZ) total artificial
      heart for bridge-to-cardiac transplantation of a heart and kidney.

PMID- 19766831
TI  - Deep hypothermic circulatory arrest for a patient with known cold agglutinins.
AB  - We report a case study of a patient with renal cell carcinoma with tumor
      extension into the right atrium. This case was complicated by the diagnosis of
      cold agglutinins and the need for deep hypothermic circulatory arrest. A
      collaborative approach yielded a positive outcome.

PMID- 19766832
TI  - Failure of percutaneous closure of prosthetic, aortic paravalvular leak.
AB  - We report the progression of aortic insufficiency after percutaneous closure of
      an aortic prosthesis paravalvular leak with the Amplatzer vascular plug (AGA Inc,
      Golden Valley, MN). Removal of the device and replacement of the aortic
      prosthesis was successfully performed. Based on operative findings, we
      hypothesize that shape mismatch between the occluder system and the leak might
      promote tearing at the end of slanted defects further enhancing the regurgitant
      area.

PMID- 19766833
TI  - Aortic valve replacement and coronary artery bypass grafting in a rare case of
      congenital hypofibrinogenemia.
AB  - Congenital hypofibrinogenemia is a rare condition. We believe that cardiac
      surgery using cardiopulmonary bypass in a patient with congenital
      hypofibrinogenemia has not been reported before. We discuss the management in a
      patient with this condition who successfully underwent an aortic valve
      replacement and coronary artery bypass grafting.

PMID- 19766834
TI  - Effects of nafamostat mesilate on coagulopathy with chronic aortic dissection.
AB  - A 65-year-old man with chronic aortic dissection experienced two massive
      subcutaneous hemorrhages. Laboratory data indicated disseminated intravascular
      coagulation, whereas a contrast computed tomographic scan revealed a dilatated
      aortic arch with a partial thrombosis at the false lumen. Because disseminated
      intravascular coagulation can be caused by chronic aortic dissection, and the
      aortic arch was 6 cm in diameter, we performed graft replacement from the
      ascending to the descending aorta in a single stage. Before graft replacement,
      nafamostat mesilate, a protease inhibitor, was administered and the disseminated
      intravascular coagulation improved. Nafamostat mesilate may be useful for
      managing disseminated intravascular coagulation associated with chronic aortic
      dissection.

PMID- 19766835
TI  - New treatment with human atrial natriuretic peptide for postoperative
      myonephropathic metabolic syndrome.
AB  - A 49-year-old man had sudden chest pain and paralysis of the lower right limb. An
      acute aortic dissection was diagnosed in a computed tomography scan and the
      patient underwent an emergency operation. After the operation, myonephropathic
      metabolic syndrome developed, and human atrial natriuretic peptide was
      administered for 11 days until the volume of daily urine output reached at least
      10,000 mL, which would facilitate limb salvage and the preservation of life
      without hemodialysis. This report documents that postoperative myonephropathic
      metabolic syndrome improved due to the strong diuretic action of human atrial
      natriuretic peptide without hemodialysis.

PMID- 19766836
TI  - Paralysis of the upper rectus abdominis muscle after video-assisted or open
      thoracic surgery: an underdiagnosed complication?
AB  - In open or video-assisted thoracic surgery, injury to one to four intercostal
      sensory nerves is a well-recognized complication. This nerve damage is a well
      defined cause for chronic postoperative pain. In this discussion, the motor
      innervation of the rectus abdominis muscle with the T7 to T12 intercostal nerves
      has been neglected. Paralysis of rectus abdominis might pose significant burden
      on patients, delay recovery, and thus warrants exploration.

PMID- 19766837
TI  - Giant cardiac lipoma in the ventricular septum involving the tricuspid valve.
AB  - We report a case with a primary giant cardiac lipoma in the right ventricle
      attached to the interventricular septum that involved the chordae of the septal
      leaflet of the tricuspid valve. As the potential for malignancy was low,
      tricuspid valve replacement and minimum tumor resection were performed to obtain
      a suitable route to the right ventricular outflow tract.

PMID- 19766838
TI  - Atypical presentation of anomalous origin of the left main coronary artery from
      the pulmonary artery.
AB  - Anomalous origin of the left main coronary artery from the pulmonary artery
      (ALCAPA) is a rare congenital anomaly that usually presents in childhood. Ninety
      percent of the patients with ALCAPA die within the first year of life without
      surgical intervention. In adults, ALCAPA is associated with left ventricular
      dysfunction, mitral regurgitation, and sudden death. The present report describes
      the case of an adult patient who presented with an abnormal stress test and
      ALCAPA was diagnosed during cardiac catheterization.

PMID- 19766839
TI  - Two-patch repair for atrioventricular septal defect with mitral aneurysm.
AB  - We experienced an unusual case of partial atrioventricular septal defect in an
      elderly patient. A preoperative ultrasonic cardiogram revealed the mitral leaflet
      pouching toward the right atrium and suggested the presence of a ventricular
      septal defect underneath the atrioventricular valve. The mitral aneurysm was
      diagnosed as a septal aneurysm on preoperative ultrasonic cardiogram. A crescent
      shaped Dacron patch (InterVascular S. A., La Ciotat Cedex, France) was placed
      beneath the atrioventricular valve to prevent rupture of the mitral aneurysm and
      support the anterior mitral leaflet by creating a new annulus. We believe that
      this is the first report describing this type of mitral aneurysm and its surgical
      repair.

PMID- 19766840
TI  - Successful surgical pulmonary artery reconstruction in arterial tortuosity
      syndrome.
AB  - The outcomes of surgical repair for diffuse pulmonary artery stenoses due to
      arterial tortuosity syndrome are unknown. We report a 1-year-old girl with
      tortuosity syndrome who presented with suprasystemic right ventricular pressure
      due to distortion and stenoses of the pulmonary artery branches. We describe the
      operative findings of this unique pathology and the surgical techniques used to
      completely reconstruct the pulmonary arterial tree, with normalization of the
      right ventricular pressure.

PMID- 19766841
TI  - Aortopexy for tracheomalacia with dextrocardia, pulmonary artery sling, and
      congenital tracheal stenosis.
AB  - We report a rare case of coexisting pulmonary artery sling, congenital tracheal
      stenosis, and dextrocardia caused by right lung hypoplasia. Successful treatment
      of severe postoperative tracheomalacia was achieved by aortopexy, aiming
      displacement of the aortic arch across orthogonally in front of the trachea due
      to dextrocardia. The aim of this surgery was different from the usual aortopexy
      for tracheomalacia, which lifts the tracheal wall with the aorta. The three
      dimensional evaluation considering the patient's associated malformations led to
      a successful result.

PMID- 19766842
TI  - Modified primary sutureless repair of total anomalous pulmonary venous connection
      in heterotaxy.
AB  - Early and late mortality remain high after palliative open heart surgery in low
      weight neonates. In addition, the need for neonatal repair and the presence of
      pulmonary venous obstruction are risk factors for mortality in right isomerism.
      We describe a modified primary sutureless repair of infracardiac total anomalous
      pulmonary venous connection in a 1,600 g neonate with heterotaxy. Endarterectomy
      of intimal hyperplasia localized to the anastomotic site was required at
      bilateral bidirectional cavopulmonary connection 6 months after the initial
      repair. The patient underwent a successful fenestrated Fontan procedure using an
      extracardiac conduit at the age of 2 years.

PMID- 19766843
TI  - Bronchial carcinoid secreting insulin-like growth factor-1 with acromegalic
      features.
AB  - Acromegaly caused by a bronchial carcinoid tumor is rare. We report a patient
      with acromegaly caused by a bronchial carcinoid tumor secreting insulin-like
      growth factor-1. The patient was treated successfully with bilobectomy.

PMID- 19766844
TI  - An unusual case of Aspergillus fibrosing mediastinitis.
AB  - Fibrosing mediastinitis due to Aspergillus is rare, particularly in the
      immunocompetent host. Fibrosing mediastinitis due to Aspergillus species in the
      immunocompetent patient can be indolent and may be treated with antifungal
      therapy rather than surgery. We present a 78-year-old nonsmoking, nondiabetic
      woman with chronic fibrosing mediastinitis due to Aspergillus. Multiple attempts
      at securing a tissue diagnosis were inconclusive. Ultimately, Aspergillus
      infection was diagnosed by a video-assisted thoracoscopic surgical biopsy. The
      patient was started on oral voriconazole, and she remains clinically stable with
      radiographic improvement. A prolonged, perhaps lifelong, course of antifungal
      therapy is planned.

PMID- 19766845
TI  - Thoracic outlet syndrome in a patient with Poland syndrome.
AB  - We report a 20-year-old man with Poland syndrome who suffered from weakness,
      pain, numbness, and discoloration in the left upper extremity. He was eventually
      diagnosed as also having thoracic outlet syndrome. The concomitance of these two
      disorders is discussed with a special emphasis on the underlying mechanisms.

PMID- 19766846
TI  - Primary pulmonary rhabdomyosarcoma in an adult with neurofibromatosis-1.
AB  - Rhabdomyosarcomas arising in various tissues associated with neurofibromatosis
      type 1 have been sporadically described in children and young adults. We report a
      unique case of primary pulmonary rhabdomyosarcoma in an adult with
      neurofibromatosis type 1. A right lower lobectomy was performed. The Intergroup
      Rhabdomyosarcoma Study IV postsurgical grouping classification was 1A. The
      patient is scheduled for chemotherapy without adjuvant radiation therapy as per
      standard pediatric protocol.

PMID- 19766847
TI  - Anomalous systemic arterial supply to separate lingular and basal segments of the
      lung: an anatomic consideration.
AB  - A 22-year-old man was referred for hemoptysis and general fatigue after exercise.
      Arteriography demonstrated an anomalous artery arising from the descending aorta
      supplying the lingular and all of the basal segments of the left lung. The
      feeding areas of the pulmonary and anomalous arteries were mutually exclusive. He
      underwent division of the anomalous artery and combined resection of the diseased
      segments. The upper division of the upper lobe and the superior segment of the
      lower lobe were spared. His symptoms were greatly improved postoperatively. The
      preoperative anatomic evaluation of anomalous vessels is crucial in surgical
      management.

PMID- 19766848
TI  - Latissimus dorsi myoclonus after video assisted thoracoscopic lung volume
      reduction.
AB  - Myoclonus as a sequel to thoracotomy has been reported, and its treatment can be
      challenging to both the patient and the surgeon. We describe a 43-year-old
      patient with chest wall pain and latissimus dorsi muscle contractions (myoclonus)
      after video-assisted thoracoscopic lung volume reduction. His symptoms remained
      refractory to benzodiazepines, nerve blockage, and botulinum toxin injection due
      to either poor compliance or lack of response to therapy. These symptoms started
      to resolve spontaneously 18 months after the procedure.

PMID- 19766849
TI  - Retained intracardiac air mimicking left atrial mass by transesophageal
      echocardiography.

PMID- 19766850
TI  - Transphrenic budding of the liver.

PMID- 19766851
TI  - Re-do aortic root replacement after an allograft aortic root replacement.
AB  - Structural degeneration of allograft aortic root is a global process. In addition
      to valvular degeneration, the allograft wall calcification poses a risk of
      systemic calcific embolization and late phase anastomotic aneurysm formation and
      rupture (anecdotal). Furthermore, the valve annulus is often small, and the
      tissues are rigid making the implantation of an adequately sized prosthesis
      within the allograft wall difficult. To avoid these issues, we routinely perform
      re-do aortic root replacement with either a mechanical valve conduit or bio-root
      composite graft. The technique has been successfully used in 22 consecutive
      patients with no operative mortality and minimal morbidity.

PMID- 19766852
TI  - Novel modification of total cavopulmonary connection for isolated hepatic vein.
AB  - A surgeon needs an innovative technique to establish a Fontan circulation for a
      patient who has a widely separated hepatic vein from the inferior vena cava. The
      inferior vena cava was redirected by placing a trimmed GoreTex baffle (W. L. Gore
      and Associates, Flagstaff, AZ) on the internal side of the atrium connecting the
      hepatic venous flow, and then directing it to the extra-atrium. Another
      extracardiac half-circumferential GoreTex baffle was sutured to the epicardial
      atrial wall and to the pulmonary artery opening. This procedure is efficacious
      for patients with an isolated hepatic vein and has advantages in terms of using
      less synthetic material in the conduit.

PMID- 19766853
TI  - Thorascopic mediastinal resection after median sternotomy and mediastinotomy.
AB  - Previous mediastinal surgery may be considered a contraindication to minimally
      invasive resection of anterior mediastinal masses. We have found video-assisted
      thoracoscopic resection of anterior mediastinal masses to be technically feasible
      after sternotomy or chamberlain procedures. Changes in positioning and port
      location may facilitate these procedures.

PMID- 19766854
TI  - Alternative technique for salvage of donor lungs with insufficient atrial cuffs.
AB  - Inadequate left atrial cuff surrounding donor pulmonary veins may present a
      technical challenge for successful lung transplantation. A simple technique for
      construction of venous anastomoses during lung transplantation when donor atrial
      cuff is lacking involves circumferential incorporation of surrounding donor
      pericardium into the anastomosis without directly suturing or augmenting donor
      venous structures.

PMID- 19766855
TI  - A review of topical hemostatic agents for use in cardiac surgery.
AB  - Postoperative hemorrhage, redo sternotomy for bleeding, and transfusion of blood
      products are all associated with poorer outcomes in cardiac surgery. Topical
      hemostatic agents are important adjuncts to reduce blood loss after cardiac
      surgery and can have a role in reducing both "surgical" and "nonsurgical
      bleeding." There are many topical hemostatic agents to choose from, and with
      several new products in this field being approved for use in the last few years,
      the aim of this review is to appraise these agents and to look at the evidence
      for their efficacy.

PMID- 19766856
TI  - Risks of tight glycemic control during adult cardiac surgery.

PMID- 19766858
TI  - Minimally invasive mitral valve surgery after previous sternotomy.

PMID- 19766861
TI  - Percutaneous patent foramen ovale/atrial septal defect closure: just because we
      can?

PMID- 19766862
TI  - Should an endovascular procedure be combined with resection for type a aortic
      dissection?

PMID- 19766865
TI  - Thrombosed-type acute aortic dissection.

PMID- 19766866
TI  - Distance alone does not define the value of the posterior mediastinal route for
      esophageal reconstruction.

PMID- 19766868
TI  - Sexual and reproductive health and climate change.

PMID- 19766869
TI  - Are medical journals getting better--or worse?

PMID- 19766870
TI  - Emergency care in the USA.

PMID- 19766871
TI  - Shall we put the world on folate?

PMID- 19766872
TI  - Francis Collins: Director of the US National Institutes of Health. Interview by
      Tony Kirby.

PMID- 19766873
TI  - Climate change is not the biggest global health threat.

PMID- 19766875
TI  - Did alcohol protect against death from breast cancer in Russia?

PMID- 19766877
TI  - Alcohol and global health: focus on acute pancreatitis needed.

PMID- 19766878
TI  - Reducing harm from alcohol: what about unrecorded products?

PMID- 19766881
TI  - Carrier screening for cystic fibrosis.

PMID- 19766882
TI  - Distinctly different purpura on different arms.

PMID- 19766883
TI  - Child undernutrition, tropical enteropathy, toilets, and handwashing.

PMID- 19766884
TI  - New treatments for multiply drug-resistant Gram-positive bacteria.

PMID- 19766885
TI  - Microbiology of drugs for treating multiply drug-resistant Gram-positive
      bacteria.
AB  - Several new antimicrobials demonstrate in vitro activity against methicillin
      resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE),
      and other Gram-positive bacteria. Data from large surveys indicate that
      linezolid, daptomycin, and tigecycline are almost universally active against
      MRSA. Linezolid and tigecycline inhibit both Enterococcus faecium and
      Enterococcus faecalis at low concentrations; daptomycin is somewhat more potent
      against the latter. The investigational agents dalbavancin and telavancin are
      more potent than vancomycin against vancomycin-susceptible organisms. Dalbavancin
      inhibits vanB type VRE at low concentrations, but is not active against vanA type
      VRE. Telavancin is less active against VRE than against vancomycin-susceptible
      enterococci, but minimum inhibitory concentrations are lower than those of
      vancomycin against VRE. With continued careful use of available antimicrobials,
      the vast majority of these organisms should remain susceptible to 1 or more of
      the agents discussed for the foreseeable future.

PMID- 19766886
TI  - Treatment options for nosocomial pneumonia due to MRSA.
AB  - Nosocomial pneumonia, which includes hospital-acquired pneumonia, ventilator
      associated pneumonia, and health care associated pneumonia, remains an important
      cause of morbidity and mortality. The continuing emergence of methicillin
      resistant Staphylococcus aureus (MRSA) as a nosocomial pneumonia pathogen is
      particularly problematic not only because of its prevalence, but also because
      antimicrobial resistance is increasingly associated with inappropriate empirical
      antibiotic therapy. As a result, intensivists are faced with the dual goals of
      providing initial accurate broad-spectrum antibiotic coverage to reduce mortality
      while minimizing the risk for the emergence of antimicrobial resistance. These
      competing goals can be achieved by using an approach that initially delivers
      liberal broad-spectrum coverage followed by de-escalation once culture results
      and serial clinical observations become available. In ventilator-associated
      pneumonia, linezolid has demonstrated favorable activity against Gram-positive
      bacteria, including MRSA, and is recommended in evidence-based guidelines as an
      alternative to vancomycin, particularly when MRSA is documented as the etiology.

PMID- 19766887
TI  - Treatments for skin and soft-tissue and surgical site infections due to MDR Gram
      positive bacteria.
AB  - Gram-positive aerobes are the most common organisms in hospitalized patients with
      skin and soft-tissue infections (SSTIs). Staphylococcus aureus is the most common
      Gram-positive aerobe among these infections with methicillin-resistant S. aureus
      (MRSA) the most common pathogen. The increased prevalence of MRSA has been noted
      in the hospital as well in the community setting. In choosing antimicrobial
      therapy, assessment of the infection and patient characteristics, such as animal
      exposure, travel history, underlying diseases, recent trauma, bites, burns, and
      water exposure, must be considered. Community-acquired MRSA strains are showing
      resistance to more antimicrobial classes, and b-lactam antibiotics can no longer
      be considered first-line therapy for community-acquired SSTIs. For more serious
      infections, there are several new antimicrobial options with good MRSA coverage,
      including linezolid, daptomycin, and tigecycline. Several agents are currently
      under clinical investigation or are being considered for approval by the US Food
      and Drug Administration, including ceftobiprole, dalbavancin, iclaprim,
      oritavancin, and telavancin.

PMID- 19766888
TI  - Infections caused by Gram-positive bacteria: a review of the global challenge.
AB  - Infections caused by multidrug-resistant Gram-positive bacteria represent a major
      public health burden, not just in terms of morbidity and mortality, but also in
      terms of increased expenditure on patient management and implementation of
      infection control measures. Staphylococcus aureus and Enterococcus spp. are
      established pathogens in the hospital environment, and their frequent multidrug
      resistance complicates therapy. The archetypal hospital "superbug", methicillin
      resistant S. aureus (MRSA), regularly attracts mass-media interest and, in many
      countries, there is political pressure to reduce MRSA infection rates, with some
      progress now being made in the United Kingdom and the United States. To compound
      these established problems, we have witnessed the emergence and spread of
      virulent clones of MRSA in the community, and of Clostridium difficile in
      hospitals. Multidrug-resistant Streptococcus pneumoniae clones are major
      community pathogens in many parts of the world, but are now being challenged by
      new conjugate vaccines. Using combinations of molecular epidemiological tools,
      which characterize the resistant isolates and their resistance determinants,
      scientists can track highly successful bacterial strains at local, national, and
      international levels. These methods have provided new insights into the evolution
      of key pathogens, and this information may aid the design of control strategies
      and vaccines. In addition, the development of new antimicrobials including
      oxazolidinones, lipopeptides, glycylcyclines, ketolides, and new generations of
      fluoroquinolones, antistaphylococcal b-lactams, and glycopeptides must remain a
      high priority for the continued effective treatment of infections caused by
      resistant strains. So far, resistance to these newer agents is identified rarely
      in surveillance programs, but occasional reports of resistance causing
      therapeutic failure (e.g., with linezolid, daptomycin, telithromycin, or newer
      fluoroquinolones) give cause for concern. The emergence of antibiotic resistance
      is inevitable, but we must seek to decrease its impact and prolong the
      effectiveness of the agents available to us.

PMID- 19766889
TI  - Health economic issues in the treatment of drug-resistant serious Gram-positive
      infections.
AB  - Escalating health care costs have stimulated a paradigm change in the way health
      care is delivered, reimbursed, and evaluated. Reducing the length of hospital
      stay and controlling the cost of new technologies and therapies are major factors
      driving health care decisions. Economic evaluations have had variable success in
      the decision-making process, partly due to the overall quality, interpretation,
      and reporting of published analyses. Compared with other Gram-positive pathogens,
      the economic impact of methicillin-resistant Staphylococcus aureus (MRSA)
      infections remains the most studied. MRSA infections clearly represent a
      significant clinical and fiscal burden and future studies analyzing cost
      effective strategies that encompass their prevention and optimal management would
      be beneficial. These studies would need to be carefully designed with clear
      objectives and explicit perspectives at the onset. Use of an appropriate
      reference group is key in the design process to measure the true impact of MRSA
      infections. Health-economic outcome data of the impact of linezolid compared with
      glycopeptides remain the most robust data available in this therapeutic area.

PMID- 19766890
TI  - Treatment of pediatric Gram-positive multidrug-resistant infections.
AB  - Gram-positive organisms are the most common cause of bacterial infections in
      infants, children, and adolescents, accounting for 80% of community-acquired and
      60% of hospital-acquired bacterial infections. Antimicrobial treatment for
      infants and children is largely empirical in both the outpatient and hospital
      settings, despite emerging resistance patterns. Effective antimicrobial treatment
      from a pharmacological perspective relies on pharmacokinetic, pharmacodynamic,
      and pharmaceutical determinants. Pediatric patients present an additional
      challenge in selecting appropriate antimicrobial treatment for a specific
      pathogen because growth from infancy to sexual maturity results in profound
      changes in antibiotic disposition. Utilizing carefully generated pharmacokinetic,
      pharmacodynamic, and pharmaceutical data, tools exist to select the appropriate
      antimicrobial agent for treatment of Gram-positive infections in pediatric
      patients.

PMID- 19766891
TI  - Linezolid: a review of safety and tolerability.
AB  - Linezolid has demonstrated activity against antibiotic-susceptible and antibiotic
      resistant aerobic Gram-positive cocci. The availability of intravenous and oral
      formulations, with near 100% bioavailability of the latter, is hoped to
      facilitate the management of multiply drug-resistant Gram-positive infections.
      Linezolid was approved for clinical use in the United States in April 2000 and
      has subsequently been approved in other countries for the management of community
      acquired and nosocomial pneumonia, complicated and uncomplicated skin and soft
      tissue infections, and infections caused by methicillin-resistant Staphylococcus
      aureus and vancomycin-resistant enterococci, including cases with concurrent
      bacteremia. Additional studies have demonstrated potential use in febrile cancer
      patients with neutropenia, and case reports have documented some efficacy in the
      management of infective endocarditis, tuberculosis, nocardiosis, and in anaerobic
      infections. Given the potential for significantly increased use of linezolid, a
      thorough review and update of its tolerability and safety profile is warranted.

PMID- 19766892
TI  - Future gazing in the management of multiply drug-resistant Gram-positive
      infection.
AB  - Gram-positive bacteria have evolved to become predominant health care associated
      pathogens. To meet this challenge, novel approaches to the development,
      prescribing, and control of antibiotics will be needed. Additional infection
      control methods must also be explored. This review discusses the challenges posed
      in particular by methicillin-resistant staphylococci and potential ways forward.

PMID- 19766893
TI  - Impairment of peripheral nerve healing after nerve repair in rats chronically
      exposed to alcohol.
AB  - BACKGROUND AND AIMS: The aim of this study was to determine the effect of chronic
      alcoholism on the healing of repaired peripheral nerve and muscle. METHODS: Group
      1 rats (n = 9) were fed with an alcohol-free modified liquid diet (MLD)
      throughout the experiment and received no nerve transection or repair. Group 2
      rats (n = 9) were fed the same isocaloric MLD and underwent nerve transection and
      repair. Group 3 (n = 7) consisted of alcoholic rats without nerve transection and
      repair and Group 4 (n = 8) consisted of alcoholic rats with nerve transection and
      repair. To assess the effects of chronic alcoholism on nerve healing, surgical
      procedures were applied to rats in Groups 2 and 4. After 2 months, posterior
      tibial nerve and gastrocnemius muscle samples were taken for histological
      analysis. RESULTS: Group 2 rats displayed a group of atrophic fibers, whereas
      Group 3 rats showed myophagocytosis and endomysial mononuclear infiltration and
      type 2 fiber atrophy. Group 4 rats displayed a large section of atrophic fibres.
      Axonal loss, prominent regenerative clusters and endoneural fibrosis occurred in
      Group 2 rats. Axonal and myelin degeneration, myelin remnants and thinly
      myelinated axons were exhibited in Group 3 rats, whereas severe axonal loss,
      myelin degeneration, regenerative clusters and endoneural fibrosis were
      discovered in Group 4. There was a significant difference in the number of
      myelinated axons among the various groups of rats. CONCLUSIONS: Our findings show
      that chronic alcoholism has a negative influence on peripheral nerve regeneration
      associated with a significant decrease in axon number and increased axonal
      degeneration.

PMID- 19766894
TI  - Epidermal growth factor promotes epidermal growth factor receptor nuclear
      accumulation by a pathway dependent on cytoskeleton integrity in human breast
      cancer cells.
AB  - BACKGROUND AND AIMS: The epidermal growth factor receptor (EGFR) is activated by
      extracellular ligands of the epidermal growth factor (EGF) family, resulting in a
      cascade of cytoplasmic signaling events. Emerging evidence indicates a mode of
      EGF signaling in which growth factor signals are transmitted via EGFR nuclear
      transport. The aim of this study was to determine whether EGF promotes EGFR
      nuclear accumulation and the role of clathrin-coated pits, EGFR kinase activity,
      caveolae microdomains and cytoskeleton integrity in breast cancer cells. METHODS:
      MCF-7 cells were treated without or with 100 ng/ml EGF for various times and
      nuclear extracts were obtained. Nuclear accumulation of EGFR was analyzed by SDS
      PAGE followed by Western blotting of nuclear extracts using an anti-EGFR Ab or
      with a phosphospecific Ab against the Tyr-1068 of EGFR and with anti-Rb Ab as the
      loading control. DNA binding activity of EGFR was analyzed by EMSA using nuclear
      extracts and a radiolabeled oligonucleotide probe representing the AT-rich
      minimal sequence (ATRS). RESULTS: EGF induces the nuclear accumulation of EGFR,
      an increase in EGFR phosphorylation at Tyr-1068 and the formation of the complex
      EGFR-DNA in MCF-7 and MDA-MB-231 breast cancer cells. In addition, EGFR nuclear
      accumulation is dependent of clathrin-coated pits, EGFR kinase activity, caveolae
      microdomains and cytoskeleton integrity. CONCLUSIONS: This study demonstrates
      that in breast cancer cells EGF promotes nuclear accumulation of EGFR and is
      dependent on clathrin-coated pits, EGFR kinase activity, caveolae microdomains
      and cytoskeleton integrity.

PMID- 19766895
TI  - Electrophysiological development of transplanted embryonic stem cell-derived
      cardiomyocytes in the hearts of syngeneic mice.
AB  - BACKGROUND AND AIMS: We undertook this study in order to investigate the
      electrophysiological properties of grafted mouse embryonic stem cell (ES)-derived
      cardiomyocytes in mouse hearts. METHODS: We generated transgenic D3 ES cells that
      carry the alpha-myosin heavy-chain promoter-driven enhanced green fluorescent
      protein (EGFP) gene. ES-derived cardiomyocytes (10 days) were purified by
      fluorescent-activated cell sorting and then transplanted into the left ventricle
      of syngeneic mice. Finally, hearts were removed and the EGFP+ cardiomyocytes were
      dissociated from the host heart for patch clamp study. RESULTS: Morphological
      studies showed that EGFP+ cardiomyocytes were round and small before
      transplantation. Majority of cells were larger and longer with clear cross
      striations at the fourth week. Colocalization of EGFP and 4',6-diamidino-2
      phenylindole-labeled nuclei of transplanted cells with cardiomyocyte markers for
      cardiac troponin T, as detected by immunofluorescent microscopy, indicated the
      survival of grafted cells. The patch clamp study revealed that the ES-derived
      cardiomyocytes possessed pacemaker-like action potential (AP) before
      transplantation. Four weeks after transplantation, grafted cells retained the
      characteristic of intermediate embryonic ventricular-like AP distinct from
      triangular AP of adult mouse ventricular myocytes, along with the loss of
      cellular excitability and downregulation of pacemaker current, suggesting that
      these grafted cells were not as mature as native ventricular cells. CONCLUSIONS:
      Transplanted ES-derived cardiomyocytes display accelerated differentiation and
      loss of automaticity, indicating that the long-term effectiveness of ES cell
      based biological pacemakers can also be problematic.

PMID- 19766896
TI  - Rosuvastatin inhibits MMP-2 expression and limits the progression of
      atherosclerosis in LDLR-deficient mice.
AB  - BACKGROUND AND AIMS: Statins have been shown to reduce morbidity and mortality of
      coronary heart disease (CHD). Matrix metalloproteinases (MMPs) have been found to
      be involved in atherosclerotic plaque growth and instability. Rosuvastatin may
      inhibit the secretion of MMP-2 and MMP-9 from vascular smooth muscle cells and
      macrophages in vitro. The present study investigated the effects of rosuvastatin
      on the progression of atherosclerosis and the expression of MMP-2/-9 in LDLR
      deficient mice. METHODS: LDLR-deficient mice were included in rosuvastatin group
      and control group on a high-fat and high-cholesterol diet. After 12 weeks, we
      randomly sacrificed and examined the atherosclerotic lesion area in aortic artery
      and aortic sinus and levels of plasma lipid, glucose and insulin and expression
      of MMP-2 and MMP-9 in the atherosclerotic plaques. RESULTS: Atherosclerotic
      lesion area was significantly decreased in rosuvastatin group vs. control group.
      Meanwhile, levels of plasma total cholesterol (TC), triglycerides (TG), low
      density lipoprotein cholesterol (LDL-C), and oxidized (ox)LDL in the rosuvastatin
      group were decreased as well as MMP-2 and MMP-9 expression in aortic arch with
      gelatin zymography and the production of MMP-2 in the aortic sinus through
      immunohistochemical methods. Levels of plasma high-density lipoprotein
      cholesterol (HDL-C), glucose and insulin were also decreased in rosuvastatin
      group but failed to achieve statistical significance compared with control group.
      Interestingly, we found that the value of HDL-C/TC ratio was increased in
      rosuvastatin group. CONCLUSIONS: Rosuvastatin inhibits the expression of MMP-2/-9
      and limits the progression of atherosclerosis in LDLR-deficient mice. This may be
      one of the pathways of rosuvastatin on atherosclerosis through which rosuvastatin
      induced its benefit to the therapy of coronary heart disease (CHD).

PMID- 19766897
TI  - Alterations of hematological variations in rats exposed to extremely low
      frequency magnetic fields (50 Hz).
AB  - BACKGROUND AND AIMS: The aim of this study was to evaluate the possible effects
      of in vivo exposure to extremely low frequency electromagnetic fields (ELF-EMF)
      on whole blood parameters (hematological parameters) in rats. METHODS: Forty
      eight female Wistar rats, obtained from the Medical Science Application and
      Research Center, Dicle University, Turkey in 2004 were divided into four separate
      groups: two exposed groups (0.97 mT, 50 and 100 days, 3h/day) and two controls
      (sham). RESULTS: Eosinophil, hemoglobin and MPV levels significantly decreased in
      rats that were exposed to EMF for 50 days. When the data for rats exposed for 50
      days and 100 days were compared, it was found that MPV levels in rats exposed for
      100 days were significantly lower. There was no significant difference in total
      leukocyte, neutrofil, lymphocyte, monocyte, eosinophil and basophil counts, or in
      erythrocyte, Hct, MCH, MCHC, RDW, PLT and PDW levels between the exposed and sham
      exposed groups. ELF-EMF exposure had no effect on body weight. Also, liver weight
      did not show any significant difference between groups. CONCLUSIONS: Our results
      indicate that the applied ELF-EMF exposure may induce slight but statistically
      significant alterations in some hematological parameters of rats, within the
      physiological range.

PMID- 19766898
TI  - Role of decreased production of interleukin-10 and interferon-gamma in
      spontaneous apoptosis of B-chronic lymphocytic leukemia lymphocytes in vitro.
AB  - BACKGROUND AND AIMS: B-chronic lymphocytic leukemia (B-CLL) is characterized by
      the progressive accumulation of small B lymphocytes that do not undergo apoptosis
      due to an underlying defect. One potential mechanism of defective apoptosis may
      be irregular cytokine production. The goal of our investigation was to determine
      in vitro production of relevant cytokines by lymphocytes of B-CLL patients.
      METHODS: Thirty untreated (stage A) B-CLL patients, as well as 20 stage B and C
      patients and 30 healthy volunteers as a control group were examined. Interleukin
      4 (IL-4), interferon-gamma (IFN-gamma), interleukin-10 (IL-10) and tumor necrosis
      factor-alpha (TNF-alpha) were measured by enzyme-linked immunosorbent assay
      (ELISA) in supernatants of lymphocyte cultures of all three investigated groups.
      The method applied for detecting apoptosis was fluorescence microscopic analysis
      using acridine orange/ethidium bromide (AO/EB) double staining. RESULTS:
      Investigation showed that in vitro lymphocyte production of IL-10 and IFN-gamma
      were significantly decreased in B-CLL patients, whereas there were no
      statistically significantly differences of IL-4 and TNF-alpha production among
      the tested groups. Compared with the spontaneous apoptosis observed in control
      subjects' lymphocytes, B-CLL lymphocytes showed increased percentages of
      apoptotic cells after incubation for 24h. Interestingly, increased spontaneous
      apoptosis of B-CLL lymphocytes was followed by decreased IL-10 and IFN-gamma
      production. Stage of disease did not influence B-CLL lymphocyte spontaneous
      apoptosis in vitro. CONCLUSIONS: These changes in cytokine production in cultures
      of B-CLL lymphocytes may be one of the potential mechanisms in the pathogenesis
      of abnormal apoptosis.

PMID- 19766899
TI  - Increased lipoprotein lipase activity in non-small cell lung cancer tissue
      predicts shorter patient survival.
AB  - BACKGROUND AND AIMS: Cumulative evidence suggests the involvement of lipoprotein
      lipase (LPL) in tumor progression. We tested the hypothesis that increased LPL
      activity in resectable non-small cell lung cancer (NSCLC) tissue and the
      increased LPL gene expression in the surrounding non-cancer lung tissue found in
      our previous study are predictors of patient survival. METHODS: Forty two
      consecutive patients with resected NSCLC were enrolled in the study. Paired
      samples of lung cancer tissue and adjacent non-cancer lung tissue were collected
      from resected specimens for baseline LPL activity and gene expression estimation.
      During a 4-year follow-up, 21 patients died due to tumor progression. One patient
      died due to a non-cancer reason and was not included in Cox regression analysis.
      RESULTS: High LPL activity in cancer tissue (relative to the adjacent non-cancer
      lung tissue) predicted shorter survival, independently of standard prognostic
      factors (p=0.003). High gene expression in the non-cancer lung tissue surrounding
      the tumor had no predictive value. CONCLUSIONS: Our study further underlines the
      involvement of cancer tissue LPL activity in tumor progression.

PMID- 19766900
TI  - Intestinal colonization with Oxalobacter formigenes and its relation to urinary
      oxalate excretion in pediatric patients with idiopathic calcium urolithiasis.
AB  - BACKGROUND AND AIM: Oxalobacter formigenes is an intestinal bacterium that
      utilizes oxalate as the only source of energy. It has been suggested that the
      lack of colonization with this organism may be a risk factor for calcium oxalate
      urolithiasis. Because this problem was not investigated in pediatric stone
      formers, we decided to assess it in our patients. METHODS: The presence of O.
      formigenes in stool samples of 76 children and adolescents (aged 4.1-18 years)
      with idiopathic calcium urolithiasis (36 with chemically confirmed calcium
      oxalate stones and 40 children with a strong clinical suspicion of this type of
      urolithiasis) was assessed using PCR method. Simultaneously, urinary oxalate
      excretion was measured in this group. Fifty healthy, age- and sex-matched
      subjects served as controls. RESULTS: O. formigenes was found in 21/76 patients
      (27.6%). In controls, frequency of colonization was similar (26%). The median 24h
      urinary oxalate excretion in patients colonized with O. formigenes was
      significantly lower in comparison with non-colonized patients, 0.319 (range 0.141
      0.546) and 0.437 (range 0.198-0.967) mmol/1.73 m(2)/24h, respectively.
      CONCLUSIONS: Higher urinary oxalate excretion in children with calcium
      urolithiasis may be a result of the absence of O. formigenes. The reasons for
      similarly low intestinal colonization with this bacterium in normal subjects and
      stone formers remain speculative. Thus, further studies are necessary to clarify
      this issue.

PMID- 19766901
TI  - Cognitive performance of school children with unilateral sensorineural hearing
      loss.
AB  - BACKGROUND AND AIMS: Some studies have shown low school performance of children
      with early-onset unilateral sensorineural hearing loss (U-SNHL). We undertook
      this study to compare cognitive performance of school-children with perinatal U
      SNHL with that of a group of bilateral normal hearing (BNH) children. METHODS: We
      performed a cross-sectional observation from our prospective study that included
      children discharged from the Neonatal Intensive Care Unit (NICU) who were
      followed to determine their hearing, language, and neurocognitive development. We
      performed audiometric studies and Stanford-Binet intelligence scale after Terman
      Merrill version examinations. Statistical comparisons were carried out with
      Student t and chi(2) tests. We calculated U-SNHL-associated relative risk with a
      95% confidence level. RESULTS: We followed 21 children with U-SNHL and 60 with
      BNH. Median age of both groups at the time of study was 7 years. Hearing loss
      severity ranged from severe to profound. Average number of days of stay at the
      NICU in the U-SNHL group was 26+/-4 days, whereas for the BNH group this was 8+/
      2 days (p<0.001). U-SNHL-associated variables included hyperbilirubinemia,
      bronchopulmonary dysplasia, furosemide exposure, and hypoglycemia. Average and
      standard deviation of total and of both Terman-Merrill intelligence subscale
      coefficients were significantly lower in the U-SNHL group. CONCLUSIONS: Children
      with U-SNHL may present lower intelligence coefficients than children with BNH.
      It is important to observe whether this handicap continues throughout the child's
      lifetime and to ascertain whether there are certain factors associated with
      reversibility of disability.

PMID- 19766902
TI  - Effect of folate supplementation on serum homocysteine and plasma total
      antioxidant capacity in hypercholesterolemic adults under lovastatin treatment: a
      double-blind randomized controlled clinical trial.
AB  - BACKGROUND AND AIMS: Hypercholesterolemia is one of the predisposing factors of
      cardiovascular diseases. A positive correlation of homocysteine (Hcy)
      concentration with total cholesterol is described. Lovastatin, one of the most
      administered agents in hypercholesterolemia, is not effective in lowering the
      level of serum Hcy and increasing serum total antioxidant capacity (TAC). This
      study was performed to evaluate the effects of folate supplementation on lowering
      Hcy level and changes of TAC in asymptomatic hypercholesterolemic adults under
      lovastatin treatment. METHODS: This was a double-blind randomized controlled
      clinical trial. Forty asymptomatic newly diagnosed hypercholesterolemic
      individuals were recruited. Patients were randomized into two groups: group A--20
      patients supplemented for 8 weeks with folate (5mg daily) and group B--20
      patients receiving placebo. Lovastatin was administered to both groups.
      Laboratory lipid profiles, serum Hcy and folate concentration, and TAC were
      measured at the beginning and after the 8(th) week of the study period. RESULTS:
      After folate supplementation in group A subjects, serum Hcy was significantly
      decreased (13.35+/-5.01 micromol/L to 8.43+/-2.52 micromol/L, p=0.001), whereas
      no significant changes occurred in group B (p>0.05). A significant increase in
      TAC was only observed in group A (1.54+/-0.24 micromol/L to 1.96+/-0.42
      micromol/L, p<0.001). CONCLUSIONS: Folate supplementation decreases the serum
      level of Hcy and increases TAC. It seems that a pharmacological dose of folate
      supplementation could potentially decrease the risk of cardiovascular diseases by
      reducing serum level of Hcy in adults with hypercholesterolemia.

PMID- 19766903
TI  - Metabolic control in type 2 diabetes is associated with sulfonylurea receptor-1
      (SUR-1) but not with KCNJ11 polymorphisms.
AB  - BACKGROUND AND AIMS: Sulfonylureas are hypoglycemic agents used for promotion of
      insulin secretion in type 2 diabetics (T2D). They bind to sulfonylurea receptor-1
      (SUR-1), which is a functional subunit of the ATP-sensitive potassium channel
      (K(ATP)). The other component of the potassium channel is Kir6.2, encoded by gene
      KCNJ11. Polymorphisms in these genes may lead to modulated response to
      sulfonylurea therapy. The aim of this study was to determine a relationship
      between SUR-1 [exon 16 (-3C/T), exon 31 (Arg1273Arg; AGG-->AGA) and exon 33
      (S1369A)] and KCNJ11 (E23K) polymorphisms and the following parameters of
      metabolic control in T2D: fasting plasma glucose (FPG), postprandial glucose
      (PPG) and HbA1c in Caucasian T2D of European origin. METHODS: A total of 228
      unrelated patients with T2D on sulfonylurea therapy were included in the study.
      Genotyping of all polymorphisms was performed by PCR-RFLP method. Biochemical
      parameters were determined using standard laboratory methods. RESULTS: There was
      no difference in FPG and PPG concentration in any of the genotype subgroups.
      However, diabetics with wild-type C/C genotype of the SUR-1 exon 16 polymorphism
      had significantly lower HbA1c concentration compared to the patients with variant
      T/T genotype [6.9 (6.2-7.7) mmol/L vs. 8.1 (6.7-8.8) mmol/L; p=0.009]. Also,
      patients with wild-type G/G genotype of the SUR-1 exon 31 polymorphism had
      significantly higher HbA1c concentration compared to the patients with variant
      A/A genotype [7.8 (6.9-8.8) mmol/L vs. 6.3 (5.7-6.8) mmol/L; p<0.001].
      CONCLUSIONS: SUR-1 exon 16 and exon 31 polymorphisms are significantly associated
      with HbA1c concentration.

PMID- 19766904
TI  - RAGE gene polymorphisms are associated with circulating levels of endogenous
      secretory RAGE but not with coronary artery disease in Chinese patients with type
      2 diabetes mellitus.
AB  - BACKGROUND AND AIMS: Engagement of the receptor for advanced glycation end
      products (RAGE) with advanced glycation end products and subsequent signaling
      play an important role in the development of diabetic complications. This
      pathophysiological effect was mitigated partially by endogenous secretory RAGE
      (esRAGE). The present study aimed to explore the possible association of RAGE
      polymorphism with serum esRAGE level and coronary artery disease (CAD) in Chinese
      patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 740
      consecutive patients with T2DM undergoing coronary angiography were enrolled. The
      severity of coronary atherosclerosis was defined as the number of diseased
      vessels; 69 bp insertion/deletion was determined by polymerase chain reactions,
      and -429 T/C, -374A/T and G82S variants were assessed by polymerase chain
      reaction-restriction fragment length polymorphism. RESULTS: Patients with
      genotypes carrying C allele of -429 T/C and G allele of G82S had significantly
      higher esRAGE levels. 82S allele was also associated with increased tumor
      necrosis factor-alpha and interleukin-6 levels in diabetic patients with CAD (all
      p <0.05), but none of the polymorphisms or haplotypes was related to the presence
      and severity of CAD. CONCLUSIONS: G82S and -429 T/C polymorphisms of RAGE were
      associated with the circulating levels of esRAGE but not with CAD in Chinese
      patients with T2DM.

PMID- 19766905
TI  - Potential link of microalbuminuria with metabolic syndrome in patients undergoing
      coronary angiography.
AB  - BACKGROUND AND AIMS: Microalbuminuria and metabolic syndrome (MetS) are both risk
      factors for cardiovascular disease.We sought to examine the relationship between
      microalbuminuria and MetS in patients undergoing coronary angiography. METHODS:
      From August 2007 to March 2008, we studied 531 patients (354 men, 66.7%)
      undergoing elective coronary angiography due to symptoms related to coronary
      artery disease. MetS was defined based on the adapted Adult Treatment Panel III
      (ATP-III A) proposed by the American Heart Association/National Heart, Lung, and
      Blood Institute, and microalbuminuria was defined as urinary albumin-to
      creatinine ratio (ACR) between 30 mg/g and 300 mg/g. RESULTS: MetS was detected
      in 39.7% of participants, 62.1% of women and 28.5% of men. Microalbuminuria was
      detected in 109 (20.5%) of participants, in 41 (12.8%) of non-MetS individuals,
      and in 68 (32.2%) of the MetS individuals. There was a significant positive
      association between the number of components of MetS and the corresponding
      prevalence of microalbuminuria (p<0.001). In patients with MetS compared to those
      without any component of MetS, multivariable-adjusted OR (95% CI) of
      microalbuminuria was 2.71 (1.71-4.29). Multiple logistic regression analyses
      revealed higher fasting blood glucose and lower HDL-cholesterol are independently
      associated with microalbuminuria. CONCLUSIONS: Our study demonstrated that
      microalbuminuria is strongly associated with MetS and that among the components
      of MetS high fasting blood glucose had the largest power to determine the risk of
      microalbuminuria in Iranian patients undergoing coronary angiography.

PMID- 19766906
TI  - Assessment of the relationship between Helicobacter pylori and lung cancer: a
      meta-analysis.
AB  - BACKGROUND AND AIMS: Helicobacter pylori infection has been thought to play a
      critical role in gastric carcinoma tumorigenesis and progression. Several studies
      have been devoted to the relationship between H. pylori infection and lung cancer
      risk and have generated inconclusive results. In this study we aimed to evaluate
      the potential association of H. pylori infection with lung cancer risk. METHODS:
      We conducted a search in Medline, OVID, EMBASE and CNKI, covering all published
      papers until October 2008. The relevant published papers were deliberately
      selected according to the established inclusion criteria for publications.
      Essential data were then extracted from the included studies and further analyzed
      by a systematic meta-analysis. RESULTS: A total of 98 papers were identified. Of
      these, four case-control studies met the inclusion criteria and thus were finally
      selected. Lung cancer risk for H. pylori infection was 3.24-fold (95% CI=1.11
      9.47) (Z=2.15, p<0.05) compared with the controls. CONCLUSIONS: The pooled data
      suggest infection of H. pylori as a potential risk factor for lung cancer.

PMID- 19766907
TI  - Pro12Ala polymorphism in PPARgamma2 associated with depression in Chinese
      nonagenarians/centenarians.
AB  - BACKGROUND AND AIMS: The Pro12Ala polymorphism of peroxisome proliferator
      activated receptor-gamma (PPARgamma) has been associated with decreased obesity,
      insulin resistance, type 2 diabetes and other age-associated diseases such as
      cognitive impairment, hypertension, cancer, osteoarthritis. Each one of these
      diseases had been linked to depression. Moreover, there is also an association
      between Pro12 Ala polymorphism in PPAR gamma2 and longevity. The aim of the study
      was to evaluate the association between Pro12 Ala polymorphism and depression in
      Chinese nonagenarians and centenarians. METHODS: The sample included 697
      unrelated Chinese nonagenarians/centenarians (aged between 90-108 years, mean
      age: 93.5+/-3.35 years; 67.2% women). The Pro12Ala variant was examined using
      polymerase chain reaction-restriction fragment length polymorphism. Depression
      was measured with brief 23-item Geriatrics Depression Scale Chinese-edition (GDS
      CD). RESULTS: In this sample, the genotype frequencies of the Pro12Ala
      polymorphism were 0% Ala12Ala, 9.2% Pro12Ala, 90.8% Pro12Pro and the prevalence
      of depression was 25.3%. Subjects who were 12Ala carriers had significantly lower
      prevalence of depression than those who were not 12Ala carriers (14.06 vs.
      26.38%, p=0.034). Subjects without depression also had a higher frequency of
      12Ala gene than those with depression (5.28 vs. 2.56%, p=0.031). Adjusting for
      certain clinical factors that may be associated with depression or with 12Ala
      carriers, multiple logistic regressions showed the 12Ala gene was associated with
      decreased incidence of depression. CONCLUSIONS: In summary, we found that among
      Chinese nonagenarians and centenarians, the Pro12Ala polymorphism in PPARgamma2
      was associated with depression and that the 12Ala gene may be a factor for
      decreased depression.

PMID- 19766908
TI  - Association of NAT2 gene polymorphisms with susceptibility to esophageal and
      gastric cancers in the Kashmir Valley.
AB  - BACKGROUND AND AIMS: The high incidence of gastrointestinal cancers in the
      Kashmir Valley has been attributed to the presence of many chemical carcinogens
      such as nitrosamines and heterocyclic amines in tobacco and salted tea. Due to
      functional polymorphisms of the N-acetyltransferase 2 (NAT2) gene, there may be
      interindividual differences in the metabolism of heterocyclic amines. We
      undertook this study to determine the influence of NAT2 gene polymorphisms
      (rs1799929, rs1799930, rs1799931) as well as their interactions with
      environmental carcinogens on the modulation of risk of esophageal and gastric
      cancers (EC and GC) in the Kashmir Valley. METHODS: A case/control study was
      performed involving 398 study subjects (182 controls, 123 EC and 93 GC). DNA
      samples were genotyped by PCR-RFLP method. RESULTS: None of the three NAT2
      polymorphic alleles was found to be independently associated with risk of EC/GC
      but haplotypes C(481)A(590)G(857) and T(481)A(590)G(857) significantly modulated
      the risk of EC and GC, respectively (OR=0.56; 95% CI=0.34-0.91; p=0.018 and
      OR=4.61; 95% CI=1.90-11.17; p=0.001). NAT2 slow acetylator genotypes (NAT2 *5,
      NAT2 *6, NAT2 *7) significantly increased the risk of esophageal squamous cell
      carcinoma (ESCC, OR=1.73; 95% CI=1.01-2.97; p=0.047). Smoking and salted tea
      consumption were independent risk factors, but they did not show any interaction
      with NAT2 slow acetylator genotypes. CONCLUSIONS: NAT2 slow acetylator genotype
      may increase susceptibility to ESCC, and NAT2 haplotypes (C(481)A(590)G(857) and
      T(481)A(590)G(857)) may predict susceptibility to EC and GC in the Kashmir
      Valley.

PMID- 19766909
TI  - Use of a cocktail regimen consisting of soluble galectin-1, rapamycin and histone
      deacetylase inhibitor may effectively prevent type 1 diabetes.
AB  - Type 1 diabetes (T1D) is an autoimmune disorder that results in destruction of
      insulin-releasing beta-cells of the pancreas. During the pathogenesis of T1D, at
      least two phases of beta-cell death occur: an initiation event wherein macrophage
      derived inflammatory cytokines induce beta-cell necrosis and release of beta-cell
      specific antigens, and a second, antigen-driven event in which T-cell-mediated
      immune response is directed against beta-cells. In contrast to macrophages and
      autoreactive T cells, regulatory T cells play a key role in inducing and
      maintaining immunological tolerance to self antigens. Therefore, modulation of
      the immune system may prevent the development of T1D. Herein, we proposed a
      cocktail regimen consisting of soluble galectin-1, rapamycin and histone
      deacetylase inhibitor (HDACi) for the treatment of T1D because (a) HDACi has been
      reported to protect against IL-1beta-mediated loss in beta-cell viability, (b)
      HDACi and rapamycin have the ability to promote the generation and function of
      regulatory T cells and thus suppress the cytotoxic T-cell function, and (c)
      administration of soluble galectin-1 can trigger apoptosis of the beta-cell
      reactive T cells. This cocktail regimen may not only block T-cell- and cytokine
      mediated autoimmunity but also restore self-tolerance to beta-cell antigens,
      therefore representing a novel alternative for treatment of T1D.

PMID- 19766910
TI  - The use of CTA in primary prevention patients is more controversial, because the
      Bayes theorem becomes important in considering diagnostic test interpretation in
      populations with a low prevalence of disease. Foreword.

PMID- 19766911
TI  - Image quality is undergoing constant refinement, and the number of
      uninterpretable coronary studies has gradually decreased from 20% to 40% using
      four-detector, to 15% to 25% with 16-detector, and is now as low as 3% to 10%
      with 64-detector systems. Preface.

PMID- 19766912
TI  - Cardiac CT: understanding and adopting a new diagnostic modality.
AB  - For many years, the holy grail in cardiac imaging was the noninvasive anatomic
      evaluation of the coronary arteries. Although functional tests allow for the
      detection of ischemia, they lack sufficient sensitivity and specificity to
      reliably exclude obstructive coronary artery disease in many symptomatic
      patients, and have practically no role in establishing the presence of non
      obstructive disease in asymptomatic subjects who may benefit from preventive
      interventions. The very short history of cardiac CT has demonstrated rapid
      technological advances and the potential to eliminate the need for invasive
      diagnostic testing in patients who have suspected coronary artery disease. This
      article reviews the history of this modality, the principles and challenges for
      its clinical implementation, and provides a preamble to this special issue of
      Cardiology Clinics.

PMID- 19766913
TI  - Diagnostic accuracy of CT coronary angiography.
AB  - There is a rich and rapidly growing literature on the diagnostic utility of
      coronary CT angiography (CTA) and its performance relative to other modalities
      such as stress testing and invasive coronary angiography. Earlier studies of 16
      slice coronary CTA showed wide variability in sensitivity (30%-95%) and some
      variability in specificity (86%-98%). With 40- and 64-slice coronary CTA, more of
      the chest is covered with each spin of the gantry, the breath hold is shorter,
      and there are fewer uninterpretable segments than with 16-slice coronary CTA. The
      very high negative predictive value is especially helpful in ruling out coronary
      artery disease in patients who have low to intermediate pretest likelihood of
      CAD.

PMID- 19766914
TI  - The prognostic value of cardiac computed tomographic angiography.
AB  - With advancements in temporal and spatial resolution, CT has excellent diagnostic
      characteristics for non-invasive evaluation of coronary artery disease in
      appropriate patients. Nevertheless, clinical usefulness of diagnostic testing
      requires not only high diagnostic accuracy but also risk stratification for
      patient management. Current guidelines for risk stratification of patients with
      coronary artery disease rely primarily upon functional testing; alternatively,
      anatomic risk stratification may also be performed with invasive coronary
      angiography. This article reviews current and emerging concepts in the prognostic
      value of cardiac CT angiography.

PMID- 19766915
TI  - Cardiac CT in the emergency department.
AB  - In the United States alone, nearly 6 million patients present annually to
      emergency departments with complaints of chest pain suggestive of acute coronary
      ischemia. Most of these patients have a non-negligible risk for acute coronary
      syndrome(s) (ACS) and undergo extended observation and workup for an ischemic
      cause. Of those admitted for extended observation, less than 30% of patients have
      true ACS. In patients with a low to intermediate probability, cardiac CT performs
      well in ruling out coronary artery disease, and American College of Cardiology
      and American Heart Association guidelines deem this application to be
      "appropriate." This article reviews the application of CT for the evaluation of
      acute chest pain the emergency department.

PMID- 19766916
TI  - Functional versus anatomic imaging in patients with suspected coronary artery
      disease.
AB  - Patients with suspected or known coronary artery disease often require evaluation
      by cardiac imaging tests. The purpose of these tests may vary according to each
      individual patient, from establishing or ruling out obstructive coronary artery
      disease as the cause of symptoms to determining the risk of future cardiac events
      and guiding the selection of medical therapy and revascularization. With the
      adoption of cardiac CT, most patients can have a complete evaluation
      noninvasively. The challenge is to determine when anatomical evaluation of
      coronary artery disease or functional evaluation of the burden of ischemia may be
      required. This article reviews the relative value of anatomical versus functional
      imaging and their complementary role in different clinical scenarios.

PMID- 19766917
TI  - Cardiac CT in asymptomatic patients at risk.
AB  - Atherosclerosis is a systemic process that can develop as early as the second or
      third decade of life. A significant percentage of patients who experience acute
      coronary syndromes often have non-obstructive coronary artery disease and thus
      cannot be diagnosed by their symptoms or conventional functional stress testing.
      It has been proposed that early detection of atherosclerosis would generate novel
      opportunities for primary prevention through changes in lifestyle or even through
      drug therapy, especially in patients at high cardiovascular risk. Calcium scoring
      is a simple, reproducible, and widely available test that has been extensively
      validated over the past two decades. In this article, the utility of calcium
      scoring and the potential application of CT coronary angiography in asymptomatic
      patients at risk are reviewed.

PMID- 19766918
TI  - Evaluation of coronary atherosclerotic plaques.
AB  - In many patients, unheralded myocardial infarction associated with a mortality of
      approximately 20% is the first manifestation of coronary artery disease.
      Approximately 40% of the population is considered to have a moderate midterm risk
      of 10% to 20%. Any of the stratification schemes suffers from a lack of accuracy
      to correctly determine the risk, and uncertainty exists regarding how to treat
      individuals who have been identified to be at intermediate risk. Other tools
      providing information about the necessity to reassure or to treat these patients
      are warranted. Currently, the assessment of the atherosclerotic plaque burden by
      CT may be able provide valid information for this cohort. This article discusses
      the potential value and limitations of cardiac CT for evaluating coronary
      atherosclerotic plaque.

PMID- 19766919
TI  - CT applications in electrophysiology.
AB  - In recent years, extraordinary advances have been made in the management of
      cardiac arrhythmias. Increasingly complex procedures are being performed, and the
      breadth of conditions for which invasive arrhythmia therapy is indicated
      continues to grow. In addition to atrial and ventricular ablation procedures for
      treating arrhythmias, implantable defibrillators and biventricular pacemakers for
      cardiac resynchronization therapy have made electrophysiology an important part
      of heart failure management.

PMID- 19766920
TI  - Evaluation of cardiac valves using multidetector CT.
AB  - Cardiac CT is an accurate and reasonable alternative modality for valvular
      imaging. It is used primarily for the evaluation of coronary artery disease;
      however, important information regarding valvular anatomy and function can be
      derived from CT. Calcification is a common CT finding in various valvular
      abnormalities and carries important diagnostic and prognostic value. In addition,
      valvular morphology, stenosis, and regurgitation also are detected on contrast
      enhanced scans, with good correlation with trans-thoracic echocardiography and
      other techniques.

PMID- 19766921
TI  - Left ventricular function, myocardial perfusion and viability.
AB  - Cardiac computed tomography is now poised to revolutionize the practice of
      cardiology. Multi-detector row CT (MDCT) has the potential to evaluate cardiac
      function, myocardial perfusion, and viability. These capabilities, combined with
      the robust ability of MDCT to noninvasively image the coronary arteries, makes
      MDCT a comprehensive tool for the evaluation of coronary artery disease and its
      anatomic and physiologic impact on the myocardium. Recent technologic advances in
      MDCT technology in regards to detector coverage, and spatial and temporal
      resolution promise to improve the capabilities of cardiac CT in the assessment of
      cardiac function, perfusion, and viability.

PMID- 19766922
TI  - Recent technologic advances in multi-detector row cardiac CT.
AB  - Recent technical advances in multi-detector row CT have resulted in lower
      radiation dose, improved temporal and spatial resolution, decreased scan time,
      and improved tissue differentiation. Lower radiation doses have resulted from the
      use of pre-patient z collimators, the availability of thin-slice axial data
      acquisition, the increased efficiency of ECG-based tube current modulation, and
      the implementation of iterative reconstruction algorithms. Faster gantry rotation
      and the simultaneous use of two x-ray sources have led to improvements in
      temporal resolution, and gains in spatial resolution have been achieved through
      application of the flying x-ray focal-spot technique in the z-direction. Shorter
      scan times have resulted from the design of detector arrays with increasing
      numbers of detector rows and through the simultaneous use of two x-ray sources to
      allow higher helical pitch. Some improvement in tissue differentiation has been
      achieved with dual energy CT. This article discusses these recent technical
      advances in detail.

PMID- 19766923
TI  - Radiation dose and safety in cardiac computed tomography.
AB  - As a result of the changes in use of imaging procedures that rely on ionizing
      radiation, the collective dose has increased by over 700%, and the annual per
      capita dose by almost 600% in recent years. It is possible that this growing use
      may have significant effects on public health. Although uncertainties exist
      related to the accuracy of estimated radiation exposure and biologic risk, there
      are measures that can be taken by the referring and the performing health care
      provider to reduce the potential risks while maintaining diagnostic accuracy.
      This article reviews the existing data regarding biologic hazards of radiation
      exposure associated with medical diagnostic testing, the methodologies used to
      estimate radiation exposure and dose, and the measures that can be taken to
      effectively reduce that exposure.

PMID- 19766924
TI  - Resilience.

PMID- 19766925
TI  - Developing distress protocols for research on sensitive topics.
AB  - Two protocols that were developed to address risks related to emotional distress
      in an ongoing, qualitative, community-based study of adolescent dating violence
      are presented. The first protocol is for use in telephone screening to identify
      individuals at high risk of adverse emotional reactions. The second protocol
      guides interviewer's responses to emotional distress expressed by participants
      during in-depth research interviews. The study is briefly described, and the
      process used to develop the protocols is discussed. The process of developing the
      protocols caused the authors to reconsider some previously held assumptions about
      human subject protections in research on sensitive topics.

PMID- 19766926
TI  - Encopresis: a guide for psychiatric nurses.
AB  - Encopresis is an elimination disorder that involves symptoms of fecal
      incontinence in children. It affects an estimated 1.5% to 7.5% of children ages 6
      to 12 and accounts for approximately 3% to 6% of psychiatric referrals. The
      etiology of encopresis is thought to be related to physiologic problems such as
      constipation; however, it is also a psychiatric diagnosis and anecdotally may
      have some association with psychiatric problems. Publications on this association
      and publications directed toward psychiatric nurses are limited. Encopresis is
      typically treated with nutritional and medical management along with behavioral
      modification. Psychiatric nurses working with patients who have encopresis in
      inpatient settings will have unique concerns and challenges. This article gives
      an overview of published literature from the past 10 years on the etiology and
      treatment of encopresis. Specific suggestions for inpatient psychiatric nurses
      based on published literature and the author's professional experience are
      provided.

PMID- 19766927
TI  - Understanding and integrating mindfulness into psychiatric mental health nursing
      practice.
AB  - The practice of mindfulness is increasingly being integrated into Western
      clinical practice within the context of psychotherapy and stress management.
      Although it is based in ancient Buddhist philosophy, there remains confusion
      about the definition, antecedents, processes, and outcomes of mindfulness
      practice. This article reviews the literature on mindfulness, with a focus upon a
      clearer definition and understanding of the processes and integration into
      psychiatric mental health nursing practice.

PMID- 19766928
TI  - Truths and myths that influence the sexual decision-making process among young
      multiethnic college women.
AB  - In the United States, half of all new human immunodeficiency virus (HIV) cases
      are among 13- to 24-year-old women. Heterosexual contact is the primary route of
      transmission (73%). Young African Americans account for 56% of reported HIV
      cases. In an earlier study, S. T. Roberts and B. L. Kennedy (2006) studied sexual
      decision making among 100 young multiethnic college women (YMCW). Participants
      reported high condom use intention (84%) but inconsistent condom use (64%).
      Participants perceived their risk of acquiring HIV and sexually transmitted
      diseases (STDs) as low; however, their actual risk was assessed as high. YMCW
      reported that alcohol and drugs impaired their judgment to practice safer sex.
      The YMCW concurrently reported that alcohol and drugs were a routine part of
      their sexual experiences. The current study examined a group of YMCW to elucidate
      the reasons that the knowledge of safer-sex practices was not put into practice.
      The authors sought insight into the lived experiences of YMCW's sexual behavioral
      choices. The qualitative study recruited 15 participants. Focus groups were
      conducted, and quantitative HIV and STD knowledge questionnaires were
      administered. The YMCW verbalized high knowledge of HIV, STDs, and safer-sex
      practices. The questionnaire scores evidenced significant knowledge deficit in
      these same categories. Themes emerged from the narrative date. Two beliefs or
      myths explained why women engaged in sex without a condom. The first belief was
      that YMCW were not in control of their sexual behavior when "being in the
      moment." The second belief was "not remembering what happened" secondary to
      alcohol use. The women reported that the myths were culturally accepted in their
      peer group; however, the YMCW knew that the myths were untrue. The YMCW expressed
      a strong desire for someone to teach them "real information" on sexuality as this
      information was missing in their health education courses.

PMID- 19766929
TI  - Nursing students' attitudes to mental health nursing: psychometric properties of
      a self-report scale.
AB  - Negative attitudes toward people experiencing mental illness and mental health
      nursing as a career option have been recognized as a major barrier to sustaining
      an adequate psychiatric nursing workforce. This article presents the findings
      from a prospective observational study that explored the relationship between
      undergraduate nursing students' (n = 688) attitudes relevant to the mental health
      field, preparedness, and career preferences after they had completed a mental
      health placement. A comparison was also made between the self-reported attitudes,
      beliefs, and preferences of two groups of students, one with and one without
      relevant clinical experience. Finally, the psychometric properties of the
      clinical evaluation component of the survey were explored because the structure
      and composition of this component have not been assessed or reported previously.
      The findings have direct implications for psychiatric-mental health education.
      They show a strong association between educational preparation, placement
      experiences, and students' attitudes toward psychiatric nursing and consumers of
      mental health services. Findings also indicated that students with clinical
      experience felt significantly more prepared for employment in the mental health
      field and significantly less anxiety surrounding mental illness than did students
      without clinical experience.

PMID- 19766930
TI  - Predictors of loneliness in U.S. adults over age sixty-five.
AB  - The purpose of this study was to examine sociodemographic and health-related
      risks for loneliness among older adults using Health and Retirement Study Data.
      Overall prevalence of loneliness was 19.3%. Marital status, self-report of
      health, number of chronic illnesses, gross motor impairment, fine motor
      impairment, and living alone were predictors of loneliness. Age, female gender,
      use of home care, and frequency of healthcare visits were not predictive.
      Loneliness is a prevalent problem for older adults in the United States with its
      own health-related risks. Future research of interventions targeting identified
      risks would enhance the evidence base for nursing and the problem of loneliness.

PMID- 19766931
TI  - Demystifying self-transcendence for mental health nursing practice and research.
AB  - Because human development is an integral aspect of life, pathways to mental
      health necessarily involve developmentally based issues or resources. This column
      provides an overview of self-transcendence as one developmentally based resource
      for mental health. The Self-Transcendence Scale is presented to encourage its use
      in mental health nursing practice and research.

PMID- 19766932
TI  - Urgent intervention needed.

PMID- 19766933
TI  - Linking adolescent sleep, brain maturation, and behavior.

PMID- 19766934
TI  - Uncovering the pathways linking depression and physical health.

PMID- 19766935
TI  - Bullying: we need to increase our efforts and broaden our focus.

PMID- 19766936
TI  - Reward-related brain function and sleep in pre/early pubertal and mid/late
      pubertal adolescents.
AB  - PURPOSE: The onset of adolescence is a time of dramatic changes, including
      changes in sleep, and a time of new health concerns related to increases in risk
      taking, sensation seeking, depression, substance use, and accidents. As part of a
      larger study examining puberty-specific changes in adolescents' reward-related
      brain function, the current article focuses on the relationship between
      functional neuroimaging measures of reward and measures of sleep. METHODS: A
      total of 58 healthy participants 11-13 years of age completed a functional
      magnetic resonance imaging scan using a guessing task with monetary rewards and 4
      days of at-home actigraphy and self-reported sleep ratings. Sleep variables
      included actigraph measures of mean weekend minutes asleep, sleep onset time, and
      sleep offset time, as well as self-reported sleep quality. RESULTS: During reward
      anticipation, less activation in the caudate (part of the ventral striatum) was
      associated with fewer minutes asleep, later sleep onset time, and lower sleep
      quality. During reward outcome, less caudate activation was associated with later
      sleep onset time, earlier sleep offset time, and lower sleep quality.
      CONCLUSIONS: It has been hypothesized that adolescents' low reactivity in reward
      related brain areas could lead to compensatory increases in reward-driven
      behavior. This study's findings suggest that sleep could contribute to such
      behavior. Because decreased sleep has been associated with risky behavior and
      negative mood, these findings raise concerns about a negative spiral whereby the
      effects of puberty and sleep deprivation may have synergistic effects on reward
      processing, contributing to adolescent behavioral and emotional health problems.

PMID- 19766937
TI  - Heterogeneity in youth depressive symptom trajectories: social stratification and
      implications for young adult physical health.
AB  - PURPOSE: The first objective of this study was to investigate young adult
      physical health implications of adolescent depressive symptom trajectories. The
      second objective was to investigate the social stratification of adolescent
      depressive symptom trajectories. METHODS: Data came from the National
      Longitudinal Study of Adolescent Health. The analysis included the identification
      of depressive symptom trajectory groups. These four groups were then compared in
      terms of socioeconomic characteristics and change in physical health problems,
      from adolescence to young adulthood. RESULTS: Youth in the chronically high,
      increasing, and decreasing depressive symptoms groups showed significantly higher
      increases in physical health problems and poorer socioeconomic characteristics
      than did the consistently low group. CONCLUSIONS: The associations of adolescent
      depressive symptom trajectory groups with changes in physical health provide
      evidence for the etiological processes through which depression influences
      physical health. Differing socioeconomic characteristics of depressive symptom
      trajectory groups suggest social stratification of trajectories.

PMID- 19766938
TI  - Depression, cortisol reactivity, and obesity in childhood and adolescence.
AB  - PURPOSE: Depression in childhood is associated with higher body mass index (BMI),
      a relative measure of overweight, and overweight is associated with cortisol
      reactivity, indexed by heightened secretion of cortisol in response to a
      stressor. The current study uses a mediation model to examine the associations
      between symptoms of depression, cortisol reactivity and BMI in a cross-sectional
      study. METHODS: Children (N = 111) 8 to 13 years old and a parent completed
      structured interviews. The Child Behavior Checklist was used to assess symptoms
      of depression, and cortisol reactivity to the Trier Social Stress Test for
      Children was measured. Physical examinations were used to determine BMI (kg/m(2))
      and pubertal stage. RESULTS: Depression was positively associated with BMI in
      both sexes. Age and pubertal stage were not significantly associated with BMI,
      nor was physical activity and BMI in a model including depression. In girls, but
      not in boys, the association between depression and BMI was mediated by cortisol
      reactivity. CONCLUSIONS: The current findings attest to the significance of
      psychologic states as potential components in models of childhood obesity, and
      provide conceptual and empirical support for the inclusion of cortisol reactivity
      in these models.

PMID- 19766939
TI  - Income inequality and school bullying: multilevel study of adolescents in 37
      countries.
AB  - PURPOSE: To examine the association between income inequality and school bullying
      in an international sample of preadolescents and to test for mediation of this
      association by the availability of social support from families, peers, and
      schools. METHODS: The study used economic data from the 2006 United Nations
      Development Program Human Development Report and survey data from the 2005/2006
      Health Behavior in School-aged Children (HBSC) study which included 66,910 11
      year-olds in 37 countries. Ecological correlations tested associations between
      income inequality and bullying among countries. Multilevel linear and ordinal
      regression analyses tested the effects of income inequality on perceived social
      support and bullying others at school. RESULTS: Income inequality was associated
      with rates of bullying among the 37 countries (r = .62). Multilevel analyses
      indicated that each standard deviation increase in income inequality corresponded
      with more frequent bullying by males (odds ratio = 1.17) and females (odds ratio
      = 1.24), less family support and school support but more peer support. Social
      support from families and schools was associated with less bullying after
      differences in wealth were taken into account; however, social support did not
      account for the association between income inequality and bullying. CONCLUSIONS:
      Countries with high income inequality have more school bullying among
      preadolescents than countries with low income inequality. Further study is needed
      to understand the mechanisms that account for this association. Findings suggest
      that adolescents in areas of wide income inequality-not only those in deprived
      schools and neighborhoods- should be a focus of anti-bullying campaigns.

PMID- 19766940
TI  - Time trends, trajectories, and demographic predictors of bullying: a prospective
      study in Korean adolescents.
AB  - PURPOSE: To illustrate time trends and trajectories of bullying and identify
      demographic predictors of bullying. METHODS: A prospective study of 1666 seventh-
      and eighth-grade students from two Korean middle schools was conducted between
      2000 and 2001. Using the Korean-Peer Nomination Inventory, bullying was
      categorized into four groups: victim, perpetrator, victim-perpetrator, and
      neither. RESULTS: Only the prevalence of male victims significantly decreased
      over the course of the study. Most students uninvolved in bullying at baseline
      remained so over the study period. In all, 52-58% of baseline victims and
      perpetrators and 74% of victim-perpetrators continued to be involved in bullying.
      Significantly more boys were involved with bullying than girls; individual
      stability of bullying behavior did not differ by gender. Shorter, heavier boys
      and those from lower SES, whose fathers had lower educational levels or whose
      mothers had higher educational levels, as well as shorter girls from Seoul or non
      intact families, were at an increased risk for bullying. CONCLUSIONS: Except for
      a modest decline in the number of male victims, participation in bullying
      (especially by victim-perpetrators) is stable over time. Along with disadvantaged
      background, distinct demographic profiles of bullying involvement by sex and
      bullying groups emerged, allowing early identification of bullying and targeting
      intervention and prevention.

PMID- 19766941
TI  - School bullying among adolescents in the United States: physical, verbal,
      relational, and cyber.
AB  - PURPOSE: Four forms of school bullying behaviors among US adolescents and their
      association with sociodemographic characteristics, parental support, and friends
      were examined. METHODS: Data were obtained from the Health Behavior in School
      Aged Children (HBSC) 2005 Survey, a nationally representative sample of grades 6
      10 (N = 7,182). The revised Olweus Bully/Victim Questionnaire was used to measure
      physical, verbal, and relational forms of bullying. Two items were added using
      the same format to measure cyber bullying. For each form, four categories were
      created: bully, victim, bully-victim, and not involved. Multinomial logistic
      regressions were applied, with sociodemographic variables, parental support, and
      number of friends as predictors. RESULTS: Prevalence rates of having bullied
      others or having been bullied at school for at least once in the last 2 months
      were 20.8% physically, 53.6% verbally, 51.4% socially, or 13.6% electronically.
      Boys were more involved in physical or verbal bullying, whereas girls were more
      involved in relational bullying. Boys were more likely to be cyber bullies,
      whereas girls were more likely to be cyber victims. African-American adolescents
      were involved in more bullying (physical, verbal, or cyber) but less
      victimization (verbal or relational). Higher parental support was associated with
      less involvement across all forms and classifications of bullying. Having more
      friends was associated with more bullying and less victimization for physical,
      verbal, and relational forms but was not associated with cyber bullying.
      CONCLUSIONS: Parental support may protect adolescents from all four forms of
      bullying. Friends associate differentially with traditional and cyber bullying.
      Results indicate that cyber bullying is a distinct nature from that of
      traditional bullying.

PMID- 19766942
TI  - Evaluation of an intervention program for anxious adolescent boys who are bullied
      at school.
AB  - PURPOSE: This study tested the efficacy of an intervention for anxious adolescent
      boys experiencing bullying at school. The cognitive-behavioral intervention
      focused on targeting individual factors that appear to increase an adolescent's
      vulnerability to bullying experiences such as anxiety, low self-esteem, and use
      of maladaptive coping strategies. METHODS: Adolescent boys reporting anxiety
      symptoms and the recent experience of being bullied at school (grades 7-10) were
      randomly assigned by group to intervention (n = 22) or wait-list (n = 24)
      conditions. Depressive and anxiety symptoms and bullying experiences were
      measured before and after the intervention, and at a 3-month follow-up for the
      intervention condition. RESULTS: The intervention was effective in significantly
      reducing adolescent's bullying experiences as well as their anxiety, depression,
      and the degree of distress associated with being bullied. Intervention gains were
      maintained at the 3-month follow-up. The intervention was not effective in
      enhancing adolescent's self-esteem or changing aggressive or avoidant responses
      to bullying situations. CONCLUSIONS: This study provides preliminary support for
      the value of individually focused interventions for boys in the effort to reduce
      the incidence of bullying within schools.

PMID- 19766943
TI  - Determination of relative timing of pubertal maturation through ordinal logistic
      modeling: evaluation of growth and timing parameters.
AB  - PURPOSE: (1) To propose a new method using statistical modeling to determine
      relative timing of pubertal maturation; (2) to validate the new method by
      evaluating its relationship with pubertal growth and timing parameters, including
      age at menarche, age onset of areolar maturation, age of peak height velocity,
      age at attainment of adult height, adult height, peak height velocity, body mass
      index, and percent body fat; and (3) to contrast the new method with relative
      timing of menarche on these pubertal parameters. BACKGROUND: The timing of
      puberty has a well-known impact on anthropometric and psychosocial outcomes.
      Multiple methods have been used to determine pubertal timing, but all with
      limitations. A uniformly applicable method is needed for different study designs
      and study populations. METHODS: Using the National Heart Lung and Blood Institute
      Growth and Health Study data, an ordinal logistic modeling was used to assess
      relative timing of pubertal maturation. RESULTS: The proposed method demonstrated
      good reliability and strong associations with all pubertal timing parameters,
      also body mass index and percent body fat. Timing was not significantly
      associated with adult height and peak height velocity. CONCLUSIONS: The proposed
      method is highly feasible, easy to implement, and valid. The study demonstrated
      important differences between the relationships of relative timing of secondary
      sexual characteristics and the timing of menarche on pubertal parameters. The
      study also demonstrates that individuals with early or late timing at one point
      of time are likely to maintain the same relative timing throughout puberty.

PMID- 19766944
TI  - Are there nutritional and other benefits associated with family meals among at
      risk youth?
AB  - PURPOSE: The literature suggests positive associations between family dinner
      frequency and dietary practices and psychosocial well-being, and inverse
      associations between family dinner frequency and overweight status among general
      adolescent populations. The present study aims to examine these associations
      among a population of adolescents at-risk of academic failure. METHODS: A
      racially diverse sample of adolescents (n = 145, 52% male, 61% nonwhite) from six
      alternative high schools (AHS) completed surveys and had their heights and
      weights measured by trained research staff. Mixed-model logistic regression
      analyses assessed associations between family dinner frequency and overweight
      status, healthy and unhealthy weight management, and food insecurity, whereas
      mixed linear models assessed associations with breakfast consumption, fruit and
      vegetable consumption, high-fat food intake, fast food intake, substance use, and
      depressive symptoms. Analyses adjusted for race/ethnicity, age, gender,
      socioeconomic status, and the random effect of school. RESULTS: Family dinner
      frequency was positively associated with breakfast consumption and fruit intake
      (p < .01 and p < .05, respectively), and inversely associated with depressive
      symptoms (p < .05). Adolescents who reported never eating family dinner were
      significantly more likely to be overweight (odds ratio [OR] = 2.8, confidence
      interval [CI] = 1.1-6.9) and food insecure (OR = 6.0, CI = 2.2-16.4) than
      adolescents who reported five to seven family meals per week. CONCLUSIONS: In
      this at-risk sample of youth, some, but not all of the benefits of family meals
      found in other studies were apparent. Intervention programs to increase the
      availability and affordability of healthful foods and promote family meals for
      families of AHS students may be beneficial.

PMID- 19766945
TI  - Association between problem gambling and conduct disorder in a national survey of
      adolescents and young adults in the United States.
AB  - PURPOSE: The purpose of this analysis is to examine the relationship between
      current problem gambling and current conduct disorder. METHODS: Data were
      analyzed for a U.S. national survey of respondents aged 14-21 years. RESULTS: A
      strong co-morbidity between current problem gambling and current conduct disorder
      was found. However, this co-morbidity was much stronger among younger
      respondents, declined in strength with increasing age, and was absent among the
      oldest respondents. Further analyses showed that early-onset problem gamblers had
      a higher risk for conduct disorder than late-onset problem gamblers. CONCLUSIONS:
      Gambling problems that emerge early are likely to be part of a general pattern of
      problem behavior, whereas gambling problems that emerge later may have an
      etiology unique to gambling.

PMID- 19766946
TI  - Estimating peer effects in adolescent smoking behavior: a longitudinal analysis.
AB  - PURPOSE: To empirically quantify the role of peer social networks in explaining
      smoking behavior among adolescents. We follow adolescents over time to examine
      whether the role of adolescent peers persists in affecting individual behaviors
      as adolescents transition into adulthood. METHODS: Using longitudinal data of a
      nationally representative sample of adolescents we use a multivariate structural
      model with school-level fixed effects to account for the problems of contextual
      effects, correlated effects, and peer selections to purge the potential biases
      from the estimates of peer influence. Our peer group measures are drawn not only
      from the nomination of close friends but also from classmates. Smoking prevalence
      among the peer groups were constructed using the peers' own reports of their
      cigarette consumption. RESULTS: Controlling for parent level characteristics and
      other demographic parameters, we find that a 10% increase in the proportion of
      classmates who smoke will increase the likelihood of smoking by more than 3%.
      Also, an increase in smoking rates among an individual's close friends by 10%
      will increase the likelihood of smoking by 5%. We find evidence to show that the
      influence of close friends from adolescence years continue to have an impact on
      smoking propensities even when a transition into adulthood is made. CONCLUSIONS:
      Our findings support the literature reporting that peer effects are important
      determinants of smoking even after controlling for potential biases in the data
      and that these effects persist into adulthood. Effective policy aimed at reducing
      smoking rates among adolescents would consider these long-lasting peer effects.

PMID- 19766947
TI  - Efficacy of abstinence promotion media messages: findings from an online
      randomized trial.
AB  - OBJECTIVE: We conducted an online randomized experiment to evaluate the efficacy
      of messages from the Parents Speak Up National Campaign (PSUNC) to promote parent
      child communication about sex. METHODS: We randomly assigned a national sample of
      1,969 mothers and fathers to treatment (PSUNC exposure) and control (no exposure)
      conditions. Mothers were further randomized into treatment and booster
      (additional messages) conditions to evaluate dose-response effects. Participants
      were surveyed at baseline, 4 weeks postexposure, and 6 months postexposure. We
      used multivariable logistic regression procedures in our analysis. RESULTS:
      Treatment fathers were more likely than control fathers to initiate conversations
      about sex at 4 weeks, and treatment fathers and mothers were more likely than
      controls at 6 months to recommend that their children wait to have sex. Treatment
      fathers and mothers were far more likely than controls to use the campaign Web
      site. There was a dose-response effect for mothers' Web site use. CONCLUSIONS:
      Using new media methods, this study shows that PSUNC messages are efficacious in
      promoting parent-child communication about sex and abstinence. Future research
      should evaluate mechanisms and effectiveness in natural settings.

PMID- 19766948
TI  - A randomized pilot study of multisystemic therapy targeting obesity in African
      American adolescents.
AB  - Adolescents with obesity (N = 48) and their caregivers were randomized to
      Multisystemic Therapy (MST) or a group weight-loss intervention. MST adolescents
      significantly reduced percents overweight and body fat, while control adolescents
      did not. Treatments such as MST that can intervene in the multiple systems that
      influence weight are worthy of further study.

PMID- 19766949
TI  - Real use or "real cool": adolescents speak out about displayed alcohol references
      on social networking websites.
AB  - Adolescents frequently display alcohol references on social networking Websites
      (SNSs). We conducted focus groups to determine adolescents' interpretations of
      these displayed alcohol references. Regardless of whether displayed alcohol
      references represent actual use, adolescents typically interpret these references
      as representing actual use and acknowledge their potential influence on peer
      behavior.

PMID- 19766950
TI  - A longitudinal comparison of body composition changes in adolescent girls
      receiving hormonal contraception.
AB  - The objective of this study was to examine body composition changes in adolescent
      girls initiating depot medroxyprogesterone acetate (DMPA), oral contraceptives,
      or no hormonal contraceptive method. At 6 months, DMPA resulted in significant
      increases in adiposity with concomitant decreases in lean body mass. Supplemental
      estrogen may lessen these DMPA effects.

PMID- 19766951
TI  - Cost-effectiveness of genotype-guided warfarin therapy for anticoagulation in
      elderly patients with atrial fibrillation.
AB  - BACKGROUND: In patients with atrial fibrillation (AF), anticoagulation with
      warfarin decreases the risk of embolic stroke by >50%. Identification of genetic
      polymorphisms in enzymes involved in the metabolism of warfarin can partially
      predict the maintenance dose and thus potentially decrease the incidence of
      bleeding episodes secondary to warfarin overdose. OBJECTIVES: The objectives of
      this study were to evaluate the potential clinical and economic outcomes of
      genotype-guided warfarin therapy in elderly patients newly diagnosed with AF and
      to identify a threshold in bleeding risk at which such therapy may be cost
      effective. METHODS: A decision tree was designed to represent the medical
      decision (pharmacogenetic testing or not) and the main clinical outcomes (embolic
      stroke, bleeding). Event rates of embolic stroke and bleeding complications were
      based on data from previously published clinical trials and an observational
      study, respectively; costs were from a third-party payer perspective; and
      utilities were from the patient perspective. It was assumed that use of pharma
      cogenetic testing would not lead the clinician to make any potentially harmful
      modifications to the regimen. RESULTS: This analysis found that any reduction in
      major bleeding as a result of pharmacogenetic testing would lead to improved
      utility. The higher costs of pharmacogenetic testing compared with no testing
      would be immediately offset by any reduction in major bleeding. CONCLUSIONS: In
      this decision analysis, genotype-guided warfarin therapy for anticoagulation in
      elderly patients with AF was potentially cost-effective, and its benefits were
      closely related to efficacy in preventing bleeding events. Clinical trials
      testing the efficacy of genotype-guided warfarin therapy are warranted.

PMID- 19766952
TI  - Treatment of hypertension in an elderly outpatient population in the Netherlands.
AB  - BACKGROUND: The treatment of older patients with hypertension has been
      controversial-in addition to uncertainty regarding appropriate blood pressure
      (BP) targets in the very old, there are concerns that excessive BP lowering could
      result in adverse events such as falls, stroke, and cognitive problems. The
      Hypertension in the Very Elderly Trial (HYVET), however, found that lowering BP
      in patients aged > or =80 years was associated with decreased morbidity and
      mortality. OBJECTIVE: This study compared the findings of HYVET with data from a
      population of elderly outpatients with hypertension in a clinical practice
      setting. METHODS: This was a retrospective study of prospectively collected data
      from patients aged > or =80 years with a history of hypertension who visited a
      geriatric diagnostic day clinic in the Netherlands in 2004. The data were
      analyzed to determine how many patients were being prescribed antihypertensive
      medication, how many would have been eligible for HYVET, how many achieved
      adequate BP control, and whether reaching BP goals was associated with the number
      and type of antihypertensive medications received or with eligibility for HYVET.
      RESULTS: During 2004, 518 patients aged > or =80 years visited the geriatric
      diagnostic day clinic, of whom 147 met the criteria for inclusion in this study.
      One hundred forty-one patients (95.9%) were receiving antihypertensive
      medication, although only 52 (35.4%) would have been eligible for HYVET.
      Dementia, which was an exclusion criterion in HYVET, was the major reason for
      ineligibility (70 [47.6%]). Greater proportions of patients in this study had
      comorbidities compared with the HYVET population (stroke: 22.4% vs 6.7%,
      respectively; myocardial infarction: 7.5% vs 3.1%; heart failure: 11.6% vs 2.9%;
      diabetes mellitus: 21.1% vs 6.8%). At the time of the clinic visit, 50.3% of
      patients had adequate BP control, as defined in HYVET (systolic BP <150 mm Hg and
      diastolic BP <80 mm Hg). Levels of BP control were similar in patients who would
      and would not have been ineligible for HYVET. Only the mean (SD) number of
      antihypertensive medications received was significantly associated with the
      achievement of BP control compared with failure to achieve adequate BP control
      (2.2 [1.0] vs 1.8 [1.1], respectively; P < 0.05). CONCLUSIONS: Based on the
      findings of this study, the benefits of treating elderly patients with
      hypertension in clinical practice may be lower than those reported by HYVET. The
      study results support the current recommendation that all patients with
      hypertension should be treated with >1 antihypertensive medication if adequate
      control is not achieved at low doses of a single medication.

PMID- 19766953
TI  - Determinants of antidepressant medication prescribing in elderly residents of
      aged care homes in Australia: a retrospective study.
AB  - BACKGROUND: Depression is underrecognized and poorly treated among older people
      living in aged care homes worldwide. Depression has been associated with higher
      rates of recurrence, disability, and death in older people. OBJECTIVES: The
      primary objective of this study was to assess the determinants of antidepressant
      medication prescribing among older people living in aged care homes in Australia.
      A further objective was to investigate the anti-depressant medications in common
      use, doses of antidepressants, and concurrent pharmacotherapy among people
      receiving antidepressants. METHODS: A random sample of 500 deidentified
      medication review reports was extracted from a database containing >165,000
      Residential Medication Management Review reports. Residents' demographic and
      clinical characteristics, medical diagnoses, and prescribed medications were
      systematically extracted from these reports. Logistic regression models were used
      to determine factors associated with the prescribing of any antidepressant,
      including tricyclic antidepressants (TCAs), selective serotonin reuptake
      inhibitors (SSRIs), and "other" antidepressants (eg, mianserin, mirtazapine,
      venlafaxine). RESULTS: The mean (SD) age of the residents was 84.0 (9.0) years.
      Seventy-five percent were female. The prevalence of antidepressant prescribing
      among these aged care home residents was 33.0%. SSRIs were more commonly
      prescribed than TCAs, monoamine oxidase inhibitors, and other antidepressants.
      Antidepressants were more likely to be prescribed in people treated for dementia
      with mood disorder (odds ratio [OR] = 9.70; 95% CI, 5.26-17.88), depression (OR =
      13.28; 95% CI, 6.44-27.36), and Parkinson's disease (OR = 3.56; 95% CI, 1.37
      9.23). SSRI prescribing was associated with dementia with mood disorder (OR =
      5.85; 95% CI, 3.19-10.72) and depression (OR = 6.44; 95% CI, 3.38-12.26). TCA
      prescribing was associated with depression (OR = 2.95; 95% CI, 1.18-7.35) and
      concurrent benzodiazepine use (OR = 2.43; 95% CI, 1.03-5.72). Other
      antidepressant prescribing was associated with dementia with mood disorder (OR =
      6.53; 95% CI, 3.15-13.50) and depression (OR = 5.00; 95% CI, 2.23-11.19).
      CONCLUSIONS: There was preferential prescribing of SSRI antidepressants among
      these older aged care home residents with depression. Cognitive impairment alone
      was not significantly associated with antidepressant prescribing; however, these
      aged care home residents with dementia and mood disorders had an increased
      likelihood of being treated with antidepressants. The prescribing of TCAs was
      significantly associated with concurrent benzodiazepine use.

PMID- 19766954
TI  - Chorea associated with gabapentin use in an elderly man.
AB  - BACKGROUND: Chorea is a hyperkinetic movement disorder characterized by
      irregular, flowing, nonstereotyped, random, involuntary movements. Huntington
      disease (HD) and drug-induced chorea account for >50% of adult-onset cases.
      Chorea associated with gabapentin, an anticonvulsant, has not been well
      documented. OBJECTIVE: The purpose of this article was to report a case of chorea
      that developed in an elderly man being treated with gabapentin for severe
      anxiety. CASE SUMMARY: A 75-year-old white man (height, 165.1 cm; weight, 65.8
      kg; body mass index, 19.6 kg/m2) with anxiety disorder not otherwise specified
      was admitted to a geriatric medicine psychiatric unit in Connecticut because of
      worsening symptoms of anxiety affecting his cognitive ability. On evaluation, the
      patient had choreiform movements involving the neck, trunk, upper and lower
      extremities, and tongue. The patient reported that symptoms began after taking
      gabapentin 300 mg PO TID (prescribed by his geriatrician) for the treatment of
      anxiety. The patient had been taking gabapentin for >1 month when the symptoms
      first appeared. There was no known family history of HD, and patient workup was
      unremarkable for other conditions (eg, vascular disease of the brain, progressive
      dementia, infectious and metabolic disorders) that might present with chorea. The
      chorea lasted for ~4 months and resolved within 2 days after gabapentin
      discontinuation. CONCLUSION: This article reports a case of chorea in an elderly
      patient who was receiving gabapentin for the treatment of anxiety. After
      gabapentin discontinuation, the chorea resolved completely, indicating a probable
      adverse drug reaction.

PMID- 19766956
TI  - Mandatory clinical trial registration.

PMID- 19766957
TI  - Comment on: Correlations between intra-abdominal pressure and obesity-related co
      morbidities.

PMID- 19766958
TI  - Evidence of executive dysfunction in extremely obese adolescents: a pilot study.
AB  - BACKGROUND: Obesity in children and adolescents is 1 of the most urgent and
      serious health threats confronting the United States. Extremely obese adolescents
      (body mass index >99th percentile for age and gender) are a unique subgroup of
      obese youth who are at considerable medical and psychosocial risk. Little is
      known about the cognitive function of extremely obese adolescents. The present
      study sought to examine the cognitive performance of a sample of extremely obese
      adolescents seeking primary treatment for weight loss. METHODS: Adolescents were
      recruited during regularly scheduled medical appointments at a children's center
      for weight management associated with a major children's hospital in the
      Southeast United States. A computerized battery of cognitive tests was
      administered to obese adolescents (body mass index >99th percentile; n = 25).
      RESULTS: Obese adolescents exhibited deficits in many cognitive domains,
      including impairment in attention and executive functions (e.g., mental
      flexibility, disinhibition) compared with the normative data. CONCLUSION:
      Although preliminary, these data have provided evidence for specific cognitive
      deficits in extremely obese adolescents. These findings highlight a need to
      determine whether early weight loss interventions, such as bariatric surgery, for
      obese adolescents could potentially prevent or reverse cognitive deficits and/or
      reduce the risk of future adverse neurocognitive outcome.

PMID- 19766959
TI  - Genome-wide association studies: hypothesis-"free" or "engaged"?
AB  - The advent of the first wave of genome-wide association studies (GWAS) provided a
      new conceptual framework in the search for variants underlying common disorders:
      a massive scan of the genome, free from underlying assumptions for biological or
      positional candidate loci, genes, and variants. Thus, GWAS have been labeled as a
      "hypothesis-free" or "agnostic" approach, overcoming the obstacles imposed by the
      incomplete understanding of disease pathophysiology. Despite undisputable
      successes of the genome-wide approach, the available output from GWAS explains
      only a fraction of disease heritability. Although strategies for tuning up the
      design and conduct of these studies have been proposed, it is probably under
      appreciated that GWAS are dependent on underlying assumptions, which account for
      important limitations of the so-called "hypothesis-free" studies. Dictated by the
      design of genotyping platforms or the analysis methodologies, the implicit
      hypotheses of GWAS and their related implications for future research are
      summarized in this commentary. Since the result of any biological experiment is
      primarily determined by the extent to which the hypotheses tested truly hold,
      unless the presumptions of GWAS are acknowledged and complementary genetic
      analysis methods are implemented, the full advantage of genomic scans of human
      variation will not be realized.

PMID- 19766960
TI  - Targeting the airway smooth muscle for asthma treatment.
AB  - Asthma is a complex respiratory disease whose incidence has increased worldwide
      in the last decade. Currently there is no cure for asthma. Although
      bronchodilator and anti-inflammatory medications are effective medicines in some
      asthmatic patients, it is clear that an unmet therapeutic need persists for a
      subpopulation of individuals with severe asthma. This chronic lung disease is
      characterized by airflow limitation, lung inflammation, and remodeling that
      includes increased airway smooth muscle (ASM) mass. In addition to its
      contractile properties, the ASM also contributes to the inflammatory process by
      producing active mediators, which modify the extracellular matrix composition and
      interact with inflammatory cells. These undesirable functions make interventions
      aimed at reducing ASM abundance an attractive strategy for novel asthma
      therapies. The following three mechanisms could limit the accumulation of smooth
      muscle: decreased cell proliferation, augmented cell apoptosis, and reduced cell
      migration into the smooth muscle layer. Inhibitors of the mevalonate pathway or
      statins hold promise for asthma treatment, because they exhibit anti
      inflammatory, antimigratory, and antiproliferative effects in preclinical and
      clinical studies, and they can target the smooth muscle. This review will discuss
      current knowledge of ASM biology and identify gaps in the field to stimulate
      future investigations of the cellular mechanisms that control ASM overabundance
      in asthma. Targeting ASM has the potential to be an innovative venue of treatment
      for patients with asthma.

PMID- 19766961
TI  - Anemia is associated with an elevated serum level of high-molecular-weight
      adiponectin in patients with type 2 diabetes independently of renal dysfunction.
AB  - Low serum adiponectin is associated with a high incidence of type 2 diabetes or
      coronary artery disease in the general population. Paradoxically, serum
      adiponectin is elevated in patients with chronic kidney disease (CKD), such as
      overt diabetic nephropathy. The current study aimed to investigate whether anemia
      was independently associated with the serum level of high-molecular-weight (HMW)
      adiponectin in patients with type 2 diabetes. We studied 207 type 2 diabetic
      patients (92 women and 115 men). Anemia was defined as a hemoglobin (Hb)
      <13.0g/dL in men and <12.0g/dL in women according to the guidelines of the World
      Health Organization (WHO). Overt nephropathy (CKD) was defined as clinical
      proteinuria and /or estimated glomerular filtration rate (eGFR) lower than
      60mL/min for more than 3 months. The diabetic patients were divided into 4 groups
      according to the presence or absence of anemia and/or CKD. Serum HMW adiponectin
      levels were measured by a sandwich enzyme-linked immunosorbent assay. In all 207
      patients with type 2 diabetes, serum total and HMW adiponectin levels were
      correlated positively with age, the duration of diabetes, high-density
      lipoprotein (HDL) cholesterol, urinary albumin, and serum erythropoietin, whereas
      negative correlations were found with body mass index, triglyceride, eGFR, Hb,
      hematocrit, and high sensitivity C-reactive protein. A stepwise regression
      analysis demonstrated that among several significant variables, Hb had the
      strongest independent influence on HMW adiponectin (beta =-0.487, P < 0.001).
      Diabetic patients of both sexes with anemia and CKD had the highest serum levels
      of HMW adiponectin among the 4 groups. In conclusion, anemia is associated with
      marked elevation of serum HMW adiponectin levels in diabetic patients who have
      CKD, and this elevation is independent of renal function.

PMID- 19766962
TI  - Upregulation of intermediate calcium-activated potassium channels counterbalance
      the impaired endothelium-dependent vasodilation in stroke-prone spontaneously
      hypertensive rats.
AB  - Endothelial dysfunction has been linked to a decrease in nitric oxide (NO)
      bioavailability and attenuated endothelium-derived hyperpolarizing factor (EDHF)
      mediated relaxation. The small (SK(Ca)) and intermediate (IK(Ca)) calcium
      activated potassium channels play a key role in endothelium-dependent relaxation.
      Because the repressor element 1-silencing transcription factor (REST) negatively
      regulates IK(Ca) expression, we hypothesized that augmented REST and decreased
      IK(Ca) expression contributes to impaired endothelium-dependent vasodilation
      associated with hypertension. Acetylcholine (ACh) responses were slightly
      decreased in small mesenteric arteries from male stroke-prone spontaneously
      hypertensive rats (SHRSPs) versus arteries from Wistar Kyoto (WKY) rats.
      Incubation with N-nitro-L-arginine methyl ester (L-NAME; 100mumol/L) and
      indomethacin (100mumol/L) greatly impaired ACh responses in vessels from SHRSP.
      Iberiotoxin (0.1mumol/L), which is a selective inhibitor of large-conductance
      K(Ca) (BK(Ca)) channels, did not modify EDHF-mediated vasodilation in SHRSP or
      WKY. UCL-1684 (0.1mumol/L), which is a selective inhibitor of SKCa channels,
      almost abolished EDHF-mediated vasodilation in WKY and decreased relaxation in
      SHRSP. 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM-34; 10mumol/L) and
      charybdotoxin (0.1mumol/L), which are both IKCa inhibitors, produced a small
      decrease of EDHF relaxation in WKY but completely abrogated EDHF vasodilation in
      SHRSP. EDHF-mediated relaxant responses were completely abolished in both groups
      by simultaneous treatment with UCL-1684 and TRAM-34 or charybdotoxin. Relaxation
      to SK(Ca)/IK(Ca) channels agonist NS-309 was decreased in SHRSP arteries. The
      expression of SK(Ca) was decreased, whereas IK(Ca) was increased in SHRSP
      mesenteric arteries. REST expression was reduced in arteries from SHRSP. Vessels
      incubated with TRAM-34 (10mumol/L) for 24h displayed reduced REST expression and
      demonstrated no differences in IK(Ca). In conclusion, IK(Ca) channel
      upregulation, via decreased REST, seems to compensate deficient activity of
      SK(Ca) channels in the vasculature of spontaneously hypertensive rats.

PMID- 19766963
TI  - Serum levels of hyaluronic acid and tissue metalloproteinase inhibitor-1 combined
      with age predict the presence of nonalcoholic steatohepatitis in a pilot cohort
      of subjects with nonalcoholic fatty liver disease.
AB  - Hyaluronic acid (HA) and tissue inhibitor of metalloproteinase 1 (TIMP-1) are
      reliable markers of liver fibrosis and are closely linked to the proinflammatory
      status. In this pilot cohort study, we attempted to identify a clinical score
      that would predict the severity of nonalcoholic fatty liver disease (NAFLD) based
      on clinical variables and serum markers of fibrosis and inflammation. The cohort
      included 46 patients with histologically confirmed NAFLD (76.1% male; mean age,
      43+/-13 years; mean body mass index [BMI], 27.8+/-3.5). Serum transforming growth
      factor beta (TGF-beta), HA, TIMP, and matrix metalloproteinase (MMP) levels were
      measured with commercial enzyme-linked immunoassay (ELISA) kits. Demographic
      features and clinical and laboratory findings were subjected to univariate and
      multivariate binary logistic regression analysis to construct the mathematical
      model. Receiver operating characteristic curve (ROC) analysis was used to
      identify a threshold value for diagnosis of NASH and to assess its sensitivity
      and specificity. Serum levels of HA and TIMP-1 were statistically different in
      patients with nonalcoholic steatohepatitis (NASH) (P<0.05). Logistic regression
      analysis of several clinical variables indicated patient age as the only
      independent predictor of NASH (odds ratio [OR], 1.129, 95% confidence interval
      [CI], 1.019-1.251, P=0.020). The mathematical model constructed on the basis of
      these results included age, TIMP-1, and HA levels. A value of 148.27 or more
      identified patients with NASH with 85.7% sensitivity, 87.1% specificity, and
      negative and positive predictive values of 96.4% and 60%, respectively. This
      model seems to represent a reliable noninvasive tool for excluding the presence
      of NASH. If validated in larger prospective cohort studies, it might be useful
      for determining when a liver biopsy is actually warranted in patients with NAFLD.

PMID- 19766964
TI  - Iron sufficient to cause hepatic fibrosis and ascites does not cause cardiac
      arrhythmias in the gerbil.
AB  - Chronic iron overload associated with hereditary hemochromatosis or repeated red
      cell transfusions is known to cause cardiac failure. Cardiac arrhythmias have
      been incidentally noted in patients with iron overload, but they are often
      dismissed as being related to comorbid conditions. Studies with anesthetized iron
      loaded gerbils using short recordings suggest a role for iron in the development
      of arrhythmias. Our goal was to characterize iron-induced arrhythmias in the
      chronically instrumented, untethered, telemetered gerbil. Electrocardiograms were
      recorded for 10 s every 30 min for approximately 6 months in iron-loaded (n=23)
      and control (n=8) gerbils. All gerbils in both groups showed evidence of frequent
      sinus arrhythmia. There was no difference in heart rate, electrocardiographic
      parameters, or number of arrhythmias per minute between groups. Gerbils rarely
      showed significant arrhythmias. Body weight and heart weight were not
      significantly different between groups, whereas liver weight increased with
      increasing iron dose in the treated group. Cardiac and hepatic iron
      concentrations were significantly increased in iron-loaded gerbils. Eight of 14
      gerbils loaded to 6.2 g/kg body weight developed ascites. We conclude that an
      iron load sufficient to cause clinical liver disease does not cause cardiac
      arrhythmias in the gerbil model of iron overload.

PMID- 19766965
TI  - Cerebrospinal fluid lactate dehydrogenase isoenzymes in children with bacterial
      and aseptic meningitis.
AB  - Differentiation of bacterial from aseptic meningitis may be difficult. Our aim
      was to determine the pattern of distribution of lactate dehydrogenase (LDH)
      isoenzymes in the cerebrospinal fluid (CSF) of patients with bacterial and
      aseptic meningitis. One hundred and fifty-seven patients with suspected
      meningitis were enrolled in the study. They were divided into 3 groups according
      to the culture- or bacterial antigen assay-proven diagnosis and CSF findings:
      bacterial meningitis (n = 31), aseptic meningitis (n = 65), and non-meningitis (n
      = 61). Total LDH level and percentages of LDH isoenzymes in the CSF were measured
      in each patient. Each group showed a distinct LDH isoenzyme distribution pattern,
      with a statistically significant difference among the groups in the percentages
      of the various isoenzymes. Compared with the non-meningitis group, total LDH
      activity in the CSF was high in the aseptic meningitis group (49.82+/-35.59 U/L,
      P < 0.001) and exaggerated in the bacterial meningitis group (944.53+/-112.3 U/L,
      P < 0.001). Low LDH-2 levels were unique to bacterial meningitis (P < 0.01),
      whereas high LDH-3 levels were characteristic of aseptic meningitis (P < 0.05).
      Both groups had low levels of LDH-1 and high levels of LDH-4 and LDH-5. In
      conclusion, the LDH isoenzyme pattern may be of clinical diagnostic value in
      meningitis, particularly when culture results are pending.

PMID- 19766966
TI  - Chapter 1. Focal adhesions: new angles on an old structure.
AB  - Focal adhesions have been intensely studied ever since their discovery in 1971.
      The last three decades have seen major advances in understanding the structure of
      focal adhesions and the functions they serve in cellular adhesion, migration, and
      other biological processes. In this chapter, we begin with a historical
      perspective of focal adhesions, provide an overview of focal adhesion biology,
      and highlight recent major advances in the field. Specifically, we review the
      different types of matrix adhesions and the role different Rho GTPases play in
      their formation. We discuss the relative contributions of integrin and syndecan
      adhesion receptors to the formation of focal adhesions. We also focus on new
      insights gained from studying focal adhesions on biomaterial surfaces and from
      the growing field of mechanotransduction. Throughout this chapter, we have
      highlighted areas of focal adhesion biology where major questions still remain to
      be answered.

PMID- 19766967
TI  - Chapter 2. Calcineurin signaling and the slow oxidative skeletal muscle fiber
      type.
AB  - Calcineurin, also known as protein phosphatase 2B (PP2B), is a calcium-calmodulin
      dependent phosphatase. It couples intracellular calcium to dephosphorylate
      selected substrates resulting in diverse biological consequences depending on
      cell type. In mammals, calcineurin's functions include neuronal growth,
      development of cardiac valves and hypertrophy, activation of lymphocytes, and the
      regulation of ion channels and enzymes. This chapter focuses on the key roles of
      calcineurin in skeletal muscle differentiation, regeneration, and fiber type
      conversion to an oxidative state, all of which are crucial to muscle development,
      metabolism, and functional adaptations. It seeks to integrate the current
      knowledge of calcineurin signaling in skeletal muscle and its interactions with
      other prominent regulatory pathways and their signaling intermediates to form a
      molecular overview that could provide directions for possible future
      exploitations in human metabolic health.

PMID- 19766968
TI  - Chapter 3. New insights into plant vacuolar structure and dynamics.
AB  - The plant vacuole is a multifunctional organelle and is essential for plant
      development and growth. The most distinctive feature of the plant vacuole is its
      size, which usually occupies over 80-90% of the cell volume in well-developed
      somatic cells, and is therefore highly involved in cell growth and plant body
      size. Recent progress in the visualization of the vacuole, together with
      developments in image analysis, has revealed the highly organized and complex
      morphology of the vacuole, as well as its dynamics. The plant vacuolar membrane
      (VM) forms not only a typically large vacuole but also other structures, such as
      tubular structures, transvacuolar strands, bulbs, and sheets. In higher plant
      cells, actin microfilaments are mainly located near the VM and are involved in
      vacuolar shape changes with the actin-myosin systems. Most recently, microtubule
      dependent regulation of vacuolar structures in moss plant cells was reported,
      suggesting a diversity of mechanisms regulating vacuolar morphogenesis.

PMID- 19766969
TI  - Chapter 4. Cytomechanics of hair basics of the mechanical stability.
AB  - Hair is a complex "cornified" multicellular tissue composed of cuticle and cortex
      cells mechanically acting as a whole. The cuticle cells overlap and cortex cells
      interdigitate, all cells being composed of different morphological elements and
      separated by the cell membrane complex (CMC). The CMC and the morphological
      elements of the cortex cells, the macrofibrils, composed of microfibrils or
      intermediate filaments (IFs), and the intermacrofibrillar and intermicrofibrillar
      cement or the amorphous matrix material determine the mechanical properties of
      hair. The IFs consist of alpha-keratin molecules being arranged in a
      sophisticated way of two parallel monomers and antiparallel and shifted dimers
      rationalized by the amino acid composition and sequence. The mechanical
      properties of hair result from mechanical interlocking effects, hydrophobic
      effects, hydrogen bridges, Coulombic interactions, and (covalent) isodipeptide
      and, in particular, disulfide bridges on a molecular level. The mechanical models
      applied to hair are based on a simple two-component system, the
      microfibril/matrix structure. An important regime of the stress-strain curve is
      the transition of the molecules of the microfibrils from the alpha-helical to the
      beta-sheet structure. Due to the longitudinal orientation of the IF molecules the
      longitudinal swelling of the fibers in water is negligible, the radial swelling,
      however, is substantial.

PMID- 19766971
TI  - Chapter 6. Application of new methods for detection of DNA damage and repair.
AB  - New methods for detecting DNA damage and repair are reviewed and their potential
      significance is discussed. These include methods based on analysis of DNA damage
      induced chromatin modifications, cytological detection of DNA repair synthesis,
      damage-induced immobilization of repair proteins and living cell imaging. Special
      attention is paid to current methods of detection of modifications of histones
      and other proteins associated with DNA double-strand breaks which represent most
      dangerous genome damage. New methods of analysis of DNA damage and repair may be
      useful in biodosimetry, early cancer diagnostics and in the analysis of
      efficiency of cancer radiation therapy and chemotherapy.

PMID- 19766972
TI  - Less may be more when choosing is difficult: choice complexity and too much
      choice.
AB  - Although consumers readily seek choice and abundance, the so-called too-much
      choice effect suggests that having many alternatives to choose from eventually
      leads to negative consequences, such as decreased post-choice satisfaction. The
      present research extends this research by highlighting the role of choice
      complexity. It is argued that too-much-choice effects are associated with choice
      complexity, which is influenced not only by the number of alternatives, but also
      by other features of the choice set, such as the number of attributes that
      alternatives are differentiated upon. These other influences of choice complexity
      may propel or hinder the emergence of too-much-choice effects. Two experiments
      tested this hypothesis by orthogonally manipulating the number of alternatives
      and the number of attributes. Results revealed a too-much-choice effect when
      alternatives were differentiated on many attributes, but not when alternatives
      were differentiated on few attributes. Implications for theory and practice are
      discussed.

PMID- 19766970
TI  - Chapter 5. Nuclear actin-related proteins in epigenetic control.
AB  - The nuclear actin-related proteins (ARPs) share overall structure and low-level
      sequence homology with conventional actin. They are indispensable subunits of
      macromolecular machines that control chromatin remodeling and modification
      leading to dynamic changes in DNA structure, transcription, and DNA repair.
      Cellular, genetic, and biochemical studies suggest that the nuclear ARPs are
      essential to the epigenetic control of the cell cycle and cell proliferation in
      all eukaryotes, while in plants and animals they also exert epigenetic controls
      over most stages of multicellular development including organ initiation, the
      switch to reproductive development, and senescence and programmed cell death. A
      theme emerging from plants and animals is that in addition to their role in
      controlling the general compaction of DNA and gene silencing, isoforms of nuclear
      ARP-containing chromatin complexes have evolved to exert dynamic epigenetic
      control over gene expression and different phases of multicellular development.
      Herein, we explore this theme by examining nuclear ARP phylogeny, activities of
      ARP-containing chromatin remodeling complexes that lead to epigenetic control,
      expanding developmental roles assigned to several animal and plant ARP-containing
      complexes, the evidence that thousands of ARP complex isoforms may have evolved
      in concert with multicellular development, and ARPs in human disease.

PMID- 19766973
TI  - Risk of mesh erosion after abdominal sacral colpoperineopexy with concomitant
      hysterectomy.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effect of concomitant
      hysterectomy at the time of abdominal sacral colpoperineopexy on the risk of mesh
      erosion with the use of type 1 polypropylene mesh. STUDY DESIGN: This was a
      retrospective case control study. All cases of vaginal mesh erosion (n = 31) were
      compared with matched control cases (n = 93) in a 3:1 ratio. Demographic data,
      concomitant procedures, and postoperative complications were compared between
      groups with the use of 2-sample Student t test and Pearson chi(2) test. RESULTS:
      The odds ratio of a vaginal mesh erosion was no different for those who underwent
      a hysterectomy at the time of abdominal sacral colpoperineopexy (odds ratio,
      0.95; 95% confidence interval, 0.41-2.18; P = .899) when potential confounders
      were similar between groups. CONCLUSION: Hysterectomy at the time of abdominal
      sacral colpoperineopexy is not a risk factor for vaginal mesh erosion with the
      use of type 1 polypropylene mesh.

PMID- 19766974
TI  - Chlamydia trachomatis, Mycoplasma genitalium, Neisseria gonorrhoeae, human
      papillomavirus, and polyomavirus are not detectable in human tissue with
      epithelial ovarian cancer, borderline tumor, or benign conditions.
AB  - OBJECTIVE: We sought to analyze the presence of the microorganisms Chlamydia
      trachomatis, Mycoplasma genitalium, Neisseria gonorrhoeae, human papillomavirus
      (HPV), and the polyomaviruses BK virus (BKV) and JC virus (JCV) in ovarian
      tissues of women with ovarian carcinomas, borderline tumors, and benign
      conditions. STUDY DESIGN: Ovarian tissue, snap-frozen and stored at -80 degrees
      C, from 186 women with benign conditions, borderline tumors, and epithelial
      ovarian cancer, as well as tissue from the contralateral ovary of 126 of these
      women, were analyzed regarding presence of C trachomatis and N gonorrhoeae
      (transcription mediated amplification), M genitalium (real-time polymerase chain
      reaction [PCR]), HPV (PCR), and BKV and JCV (PCR). RESULTS: All the tissue
      samples studied were found negative for the microorganisms analyzed. CONCLUSION:
      C trachomatis, M genitalium, N gonorrhoeae, HPV, and the polyomaviruses BKV and
      JCV are not detectable in ovarian tissues either from women with benign
      conditions and borderline tumors or from women with ovarian cancer.

PMID- 19766975
TI  - Psychosocial stress during pregnancy.
AB  - OBJECTIVE: We sought to identify factors associated with high antenatal
      psychosocial stress and describe the course of psychosocial stress during
      pregnancy. STUDY DESIGN: We performed a cross-sectional analysis of data from an
      ongoing registry. Study participants were 1522 women receiving prenatal care at a
      university obstetric clinic from January 2004 through March 2008. Multiple
      logistic regression identified factors associated with high stress as measured by
      the Prenatal Psychosocial Profile stress scale. RESULTS: The majority of
      participants reported antenatal psychosocial stress (78% low-moderate, 6% high).
      Depression (odds ratios [OR], 9.6; 95% confidence interval [CI], 5.5-17.0), panic
      disorder (OR, 6.8; 95% CI, 2.9-16.2), drug use (OR, 3.8; 95% CI, 1.2-12.5),
      domestic violence (OR, 3.3; 95% CI, 1.4-8.3), and having > or =2 medical
      comorbidities (OR, 3.1; 95% CI, 1.8-5.5) were significantly associated with high
      psychosocial stress. For women who screened twice during pregnancy, mean stress
      scores declined during pregnancy (14.8 +/- 3.9 vs 14.2 +/- 3.8; P < .001).
      CONCLUSION: Antenatal psychosocial stress is common, and high levels are
      associated with maternal factors known to contribute to poor pregnancy outcomes.

PMID- 19766976
TI  - It's not what you think: pain in the genital area was followed by ulceration.

PMID- 19766977
TI  - Osteopathic manipulative treatment of back pain and related symptoms during
      pregnancy: a randomized controlled trial.
AB  - OBJECTIVE: To study osteopathic manipulative treatment of back pain and related
      symptoms during the third trimester of pregnancy. STUDY DESIGN: A randomized,
      placebo-controlled trial was conducted to compare usual obstetric care and
      osteopathic manipulative treatment, usual obstetric care and sham ultrasound
      treatment, and usual obstetric care only. Outcomes included average pain levels
      and the Roland-Morris Disability Questionnaire to assess back-specific
      functioning. RESULTS: Intention-to-treat analyses included 144 subjects. The
      Roland-Morris Disability Questionnaire scores worsened during pregnancy; however,
      back-specific functioning deteriorated significantly less in the usual obstetric
      care and osteopathic manipulative treatment group (effect size, 0.72; 95%
      confidence interval, 0.31-1.14; P = .001 vs usual obstetric care only; and effect
      size, 0.35; 95% confidence interval, -0.06 to 0.76; P = .09 vs usual obstetric
      care and sham ultrasound treatment). During pregnancy, back pain decreased in the
      usual obstetric care and osteopathic manipulative treatment group, remained
      unchanged in the usual obstetric care and sham ultrasound treatment group, and
      increased in the usual obstetric care only group, although no between-group
      difference achieved statistical significance. CONCLUSION: Osteopathic
      manipulative treatment slows or halts the deterioration of back-specific
      functioning during the third trimester of pregnancy.

PMID- 19766978
TI  - Cardiovascular responses to maternal betamethasone administration in the
      intrauterine growth-restricted ovine fetus.
AB  - OBJECTIVE: The objective was to characterize the effect of glucocorticoid
      treatment on fetal organ blood flow and regional cerebral blood flow in normally
      grown fetuses and fetuses with intrauterine fetal growth restriction (IUGR).
      STUDY DESIGN: Studies were undertaken in both control and IUGR fetal sheep;
      growth restriction was induced by ligation of 1 umbilical artery. Fetuses
      received colored microspheres for organ blood flow calculations before and after
      2 maternal betamethasone injections (BM1 and BM2). RESULTS: Following BM1,
      cardiac output was significantly decreased in the control fetuses and blood flow
      to the heart and placenta was unchanged, whereas total cerebral blood flow was
      significantly decreased (P<.001), consistent with cerebral vasoconstriction. In
      the fetuses with IUGR, the cardiac output was significantly increased at +33
      hours relative to BM1, and blood flow was increased in all organs; notably, there
      was a 2-fold increase in cerebral blood flow (P=.03). CONCLUSION: The
      cardiovascular response of the fetus with IUGR to glucocorticoids is profoundly
      different from the control fetuses, which may induce both short- and long-term
      injury.

PMID- 19766979
TI  - Maternal activity restriction and the prevention of preterm birth.
AB  - Activity restriction is 1 of the most common interventions used in obstetrics.
      Although it is used for many reasons, 1 of the most common is to prevent preterm
      birth in those at risk. This review of the literature describes the potential
      advantages, disadvantages, and efficacy of activity restriction for the
      prevention of preterm birth.

PMID- 19766980
TI  - Validation of serum biomarkers for detection of early- and late-stage endometrial
      cancer.
AB  - OBJECTIVE: The objective of this study was to determine the efficacy of 3
      previously described ovarian cancer serum biomarkers (apolipoprotein-1 [ApoA-I],
      prealbumin [TTR], transferrin [TF]) in the detection of endometrioid and
      papillary serous adenocarcinoma of the endometrium. STUDY DESIGN: ApoA-I, TTR,
      and TF levels were measured in serum samples that were obtained from 433
      individuals that included 90 women with normal endometrium, 210 women with early
      stage endometrial cancer, and 133 women with late-stage endometrial cancer.
      Multivariate regression models were constructed to evaluate the usefulness of the
      biomarkers in the detection of endometrial cancer. RESULTS: ApoA-I, TTR, and TF
      distinguished normal samples from early-stage endometrial cancer with a
      sensitivity of 71% (specificity, 88%) and normal samples from late stage
      endometrial cancer with a sensitivity of 82% (specificity, 86%). CONCLUSION: The
      biomarker panel that consists of ApoA-I, TTR, and TF may prove to be a useful
      clinical tool for the detection of endometrial cancer.

PMID- 19766981
TI  - Change in urethral sphincter neuromuscular function during pregnancy persists
      after delivery.
AB  - OBJECTIVE: The purpose of this study was to assess the effect of pregnancy and
      first vaginal delivery on urethral striated sphincter neuromuscular function.
      STUDY DESIGN: Quantitative electromyographic (EMG) interference pattern analysis
      of the urethral sphincter of 23 nulligravidas and 31 third trimester
      primigravidas allowed comparison of mean motor unit parameters before term
      vaginal delivery and postpartum. RESULTS: Mean electromyographic interference
      pattern parameters in the primigravidas were significantly lower than
      nulligravidas even antepartum, with decreased turns, lower amplitude, and less
      activity. The only significant change at 6 months' postpartum was further decline
      in number of turns resulting in a further decrease in turns:amplitude. All other
      electromyographic abnormalities persisted at 6 months' postpartum and remained
      abnormal compared to the nulligravidas. CONCLUSION: Urethral sphincter
      neuromuscular function changed significantly during pregnancy and these changes
      persisted postpartum. Lack of recovery 6 months' postpartum suggests a
      physiologic impact of pregnancy itself on future risk of urinary incontinence.

PMID- 19766982
TI  - Tea consumption and risk of endometrial cancer: a metaanalysis.
AB  - OBJECTIVE: The objective of the study was to assess the association between tea
      consumption and endometrial cancer. STUDY DESIGN: Studies were identified by
      searching PubMed and EMBASE databases and screening the references of retrieved
      articles. The summary relative risk (RR) with 95% confidence interval (CI) was
      calculated. RESULTS: The combined RR for ever drinkers vs non/lowest drinkers was
      0.85 (95% CI, 0.77-0.94). Compared with non/lowest drinkers, the summary RR was
      0.88 (95% CI, 0.78-0.98) for low to moderate drinkers and 0.75 (95% CI, 0.64
      0.88) for high drinkers. An increase in tea intake of 2 cups/day was associated
      with a 25% decreased risk of endometrial cancer. In subgroup analyses, tea
      consumption was significantly associated with reduced endometrial cancer risk in
      Asian studies and studies using interviewing techniques. Furthermore, the
      protective effect of green tea on endometrial cancer seemed more evident than
      that of black tea. CONCLUSION: Findings from this metaanalysis suggest that tea
      consumption may reduce the risk of endometrial cancer. Because of the limited
      number of studies, further prospective studies are needed to explore the
      protective effect of tea on endometrial cancer.

PMID- 19766983
TI  - Procidentia-induced perinephric and subcutaneous abscesses.
AB  - Total uterine prolapse, or procidentia, rarely causes obstructive uropathy.
      Procidentia-induced perinephric abscess has not been reported to date. We present
      a case of perinephric and subcutaneous abscesses secondary to procidentia-induced
      hydronephrosis and forniceal rupture of Staphylococcus aureus-infected urine.

PMID- 19766984
TI  - Variability of the retropubic space anatomy in female cadavers.
AB  - OBJECTIVE: To characterize the anatomic relationships of clinically relevant
      structures in the retropubic space. STUDY DESIGN: Detailed dissections were
      performed in 15 female cadavers. RESULTS: The obturator vein was the closest of
      the obturator neurovascular structures to the ischial spine, median distance 3.4
      cm (range, 1.8-4.8 cm). The vesical venous plexus included 2-5 rows of veins that
      coursed within the paravaginal tissue parallel to the bladder and drained into
      the internal iliac veins. The internal iliac vein was formed cephalad to the
      level of the ischial spine; the closest distance between these structures was 3.8
      cm (1.6-6.2 cm). CONCLUSION: The complexity and proximity of the large internal
      iliac venous system to the bony landmarks used for passage of trocars is
      described in this study. A thorough understanding of the vascular anatomy in this
      space should help avoid serious operative complications.

PMID- 19766985
TI  - Plasma level of soluble c-Met is tightly associated with the clinical risk of
      preeclampsia.
AB  - OBJECTIVE: The objective of the study was to examine the relevance of the soluble
      form c-Met (sMet) with the clinical risk for severe preeclampsia. STUDY DESIGN:
      This prospective case-control study was performed by using plasma derived from 44
      preeclamptic and 51 uncomplicated pregnant women. Plasma concentration of sMet
      was measured with specific enzyme-linked immunosorbent assay, and the predictive
      values were determined based on the receiver-operating characteristic (ROC)
      curves analysis. RESULTS: Plasma s-Met level in normal pregnant women changed in
      a gestation-dependent manner, peaking at weeks 19-24. In women with severe
      preeclampsia, the circulating sMet level was significantly lower than that in the
      gestational stage-matched controls during gestational weeks 15-30. The ROC curve
      analysis revealed a significant correlation between plasma sMet level and the
      risk of developing severe preeclampsia. CONCLUSION: Plasma sMet could serve as a
      potential biomarker for predicting severe preeclampia at early second trimester
      of pregnancy.

PMID- 19766986
TI  - Exposure assessment of kneeling work activities among floor layers.
AB  - The objective of this study was to quantify the proportion of kneeling work
      activities among floor layers and to assess external knee joint forces in five
      different kneeling work positions. Thirty-three floor layers were videotaped
      discontinuously and four floor layers were videotaped continuously for a whole
      working day. External knee forces were measured in five different kneeling work
      positions in ten floor layers using Computer Dynography. The study showed that
      floor layers spent a high percentage of time in knee-straining work positions.
      Kneeling work tasks, particularly gluing and crawling caused high external knee
      forces ranging from 0.3 Newton (SD 0.2) times body weight when floor layers were
      kneeling back on the heels, to 3.5 Newton (SD 0.3) times body weight in the
      crawling work position. The study highlights the need for prevention by
      minimizing the amount of kneeling work positions among floor layers.

PMID- 19766987
TI  - The impact of dissociation and depression on the efficacy of prolonged exposure
      treatment for PTSD.
AB  - This study investigates the impact of dissociative phenomena and depression on
      the efficacy of prolonged exposure treatment in 71 patients with posttraumatic
      stress disorder (PTSD). Diagnoses, comorbidity, pretreatment depressive symptoms,
      PTSD symptom severity, and dissociative phenomena (trait dissociation, numbing,
      and depersonalization) were assessed at pretreatment using semi-structured
      interviews and questionnaires. In a pretreatment behavioral exposure test,
      patients were imaginally exposed to (part of) their trauma memory for 9 min,
      during which subjective fear was assessed. At posttreatment and 6 months follow
      up PTSD, depressive and dissociative symptoms were again assessed in the
      completers (n = 60). Pretreatment levels of dissociative and depressive symptoms
      were similar in dropouts and completers and none of the dissociative phenomena
      nor depression predicted improvement. Against expectations, dissociative
      phenomena and depression were associated with enhanced rather than impeded fear
      activation during the behavioral exposure test. However, these effects
      disappeared after controlling for initial PTSD severity. Hence, rather than
      supporting contraindication, the current results imply that patients presenting
      with even severe dissociative or depressive symptoms may profit similarly from
      exposure treatment as do patients with minimal dissociative or depressive
      symptoms.

PMID- 19766988
TI  - Microwave-assisted efficient synthesis of glucose-based 3-acetyl-5-alkyl-2,3
      dihydro-1,3,4-oxadiazole derivatives catalyzed by sodium acetate.
AB  - A novel approach to synthesize glucose-based 3-acetyl-5-alkyl-2,3-dihydro-1,3,4
      oxadiazoles with the assistance of microwave irradiation was developed. The
      effects of different catalysts on the heterocyclization process were
      investigated, and the reaction conditions were optimized, with NaOAc emerging as
      the catalyst of choice. Under the optimized conditions, a series of novel 3
      acetyl-5-alkyl-2,3-dihydro-1,3,4-oxadiazole derivatives 4 and 5 were successfully
      synthesized from hydrazones 2 and 3. The absolute configurations of hydrazones 2,
      3 and oxadiazoles 4, 5 were confirmed by NMR spectroscopic data. The ratio of the
      isomers 4 and 5 was approximately 1:1.

PMID- 19766989
TI  - Structural characterization of an O-linked tetrasaccharide from Pseudomonas
      syringae pv. tabaci flagellin.
AB  - The flagellin of Pseudomonas syringae pv. tabaci is a glycoprotein that contains
      O-linked oligosaccharides composed of rhamnosyl and 4,6-dideoxy-4-(3
      hydroxybutanamido)-2-O-methylglucosyl residues. These O-linked glycans are
      released by hydrazinolysis and then labeled at their reducing ends with 2
      aminopyridine (PA). A PA-labeled trisaccharide and a PA-labeled tetrasaccharide
      are isolated by normal-phase high-performance liquid chromatography. These
      oligosaccharides are structurally characterized using mass spectrometry and NMR
      spectroscopy. Our data show that P. syringae pv. tabaci flagellin is glycosylated
      with a tetrasaccharide, 4,6-dideoxy-4-(3-hydroxybutanamido)-2-O-methyl-Glcp-(1-
      >3)-alpha-L-Rhap-(1-->2)-alpha-L-Rhap-(1-->2)-alpha-L-Rha-(1-->, as well a
      trisaccharide, 4,6-dideoxy-4-(3-hydroxybutanamido)-2-O-methyl-Glcp-(1-->3)-alpha
      L-Rhap-(1-->2)-alpha-L-Rha-(1-->, which was identified in a previous study.

PMID- 19766990
TI  - Efficient synthesis of D-xylo and D-ribo-phytosphingosines from methyl 2-amino-2
      deoxy-beta-D-hexopyranosides.
AB  - A general and flexible synthetic approach to biologically important 5,6
      unsaturated C(18)-phytosphingosines was developed via olefin cross-metathesis
      employing truncated C(6)-phytosphingosines as the key intermediates. These were
      efficiently prepared in high yields by zinc-mediated reductive opening of methyl
      2-amino-2-deoxy-beta-hexopyranosides. [structure: see text]

PMID- 19766991
TI  - Several transition states from (4)C(1) to skew conformations of beta-D
      glucopyranose.
AB  - The interconversion pathways in the ring distortion of beta-D-glucopyranose were
      investigated using density functional calculations. We examined the energies of
      several conformers of beta-D-glucopyranose and tried to obtain the transition
      state conformation and determine the pathway between a (4)C(1) chair and some
      distorted ring conformers. The results showed that two E(3)/(2)H(3) conformations
      and one E(3)/(4)H(3) conformation were transition states in such ring puckering.
      The transition state with the lowest energy conformation is the E(3)/(2)H(3) ring
      conformation with the side-chain conformation of r-ggG(+). Intrinsic reaction
      coordinate calculations indicated that the E(3)/(2)H(3) conformation with the
      lowest conformational energy is a transition state of the ring interconversion
      path between the conformations of (4)C(1) and (2)S(O)/B(3,O). The energy barrier
      of this interconversion was 6.13 kcal/mol. As far as we know, this is the first
      example of finding pathways for an interconversion of glucopyranose ring
      puckering at the level of a quantum chemical calculation.

PMID- 19766992
TI  - [Multiple splenic abscesses].

PMID- 19766993
TI  - An examination of Nubian and Egyptian biological distances: support for
      biological diffusion or in situ development?
AB  - Many authors have speculated on Nubian biological evolution. Because of the
      contact Nubians had with other peoples, migration and/or invasion (biological
      diffusion) were originally thought to be the biological mechanism for skeletal
      changes in Nubians. Later, a new hypothesis was put forth, the in situ
      hypothesis. The new hypothesis postulated that Nubians evolved in situ, without
      much genetic influence from foreign populations. This study examined 12 Egyptian
      and Nubian groups in an effort to explore the relationship between the two
      populations and to test the in situ hypothesis. Data from nine cranial nonmetric
      traits were assessed for an estimate of biological distance, using Mahalanobis
      D(2) with a tetrachoric matrix. The distance scores were then input into
      principal coordinates analysis (PCO) to depict the relationships between the two
      populations. PCO detected 60% of the variation in the first two principal
      coordinates. A plot of the distance scores revealed only one cluster; the Nubian
      and Egyptian groups clustered together. The grouping of the Nubians and Egyptians
      indicates there may have been some sort of gene flow between these groups of
      Nubians and Egyptians. However, common adaptation to similar environments may
      also be responsible for this pattern. Although the predominant results in this
      study appear to support the biological diffusion hypothesis, the in situ
      hypothesis was not completely negated.

PMID- 19766994
TI  - Depression and protective factors of mental health in people with hepatitis C: a
      questionnaire survey.
AB  - BACKGROUND: Most studies investigating the effects of chronic hepatitis C (HCV)
      infection on the central nervous system have focused on cognitive impairment or
      on the health-related quality of life, but only few on depression. OBJECTIVES:
      This study investigated depression in HCV-infected people. Sense of coherence and
      social support were surveyed as protective factors of mental health. METHODS: In
      a cross-sectional study-design, 81 HCV-infected people with mild liver disease,
      who were not receiving antiviral therapy, were surveyed by validated measures.
      Anxiety (HADS), depression (BDI), psychopathological symptoms (SCL-90-R), social
      support (F-SozU) and resilience (SOC) were assessed. RESULTS: Higher levels of
      depression than normal controls (p=.001) and a wide range of psychological
      symptoms were associated with HCV infection. Women, single participants, and
      persons with a shorter interval after first diagnosis exhibited significantly
      higher scores of depression. Gender and sense of coherence predicted depression
      scores in HCV people (R(2)=.42, p<.001). CONCLUSIONS: The expression of
      depression in HCV-infected people is modulated not only by biological but also by
      psychological factors of mental health. Sense of coherence as a protective factor
      has a significant impact on the degree of depression. Furthermore, the high
      prevalence of depression and anxiety among persons not receiving antiviral
      therapy justifies psychosocial screening and support for HCV people independent
      of antiviral therapy.

PMID- 19766995
TI  - [Urinary diversion after cystectomy: the Bricker uretero-ileostomy].

PMID- 19766996
TI  - [Polytrauma: a therapeutic and logistical approach].
AB  - This work aims to define a strategy for the management of polytrauma based on
      findings from a review of the recent literature. After a definition of
      terminology, we address the modes of injury, pathophysiology, and the different
      phases in the management of polytrauma. We assess the results of current
      management of polytrauma in developed countries and stress the need for
      improvement in trauma systems and therapeutic interventions in order to achieve
      better results.

PMID- 19766997
TI  - [Very late development of hepatic metastases].

PMID- 19766998
TI  - High expression level of Toll-like receptor 2 on monocytes is an important risk
      factor for arteriosclerotic disease.
AB  - BACKGROUND: Toll-like receptors (TLRs) recognize pathogen-associated molecular
      patterns to initiate an innate immune response. We previously reported
      upregulation of TLR2 expression level on monocytes of stable angina pectoris
      patients with significant coronary artery disease (CAD) relative to control
      patients without significant CAD. In this study we aimed to determine whether
      high level of Toll-like receptor 2 (TLR2) is a risk factor for atherogenesis,
      independent of established risk factors including smoking, diabetes mellitus
      (DM), hypertension (HT), and hyperlipidemia (HL). METHODS: TLR2 expression level
      on circulating monocyte surfaces was measured by using our developed flow
      cytometry assay. Patients were classified into two groups: "Arteriosclerotic
      disease" group (n=108) and "Control" group (n=70). Patients of the first group
      had arteriosclerotic disease such as CAD, aortic aneurysm, or peripheral arterial
      disease (PAD). The "Control" group was sex- and age-matched to the
      "Arteriosclerotic disease" group. RESULTS: TLR2 expression was significantly
      higher in the "Arteriosclerotic disease" group than in the "Control" group
      (p<0.001). Multivariate ordinal logistic regression analysis was performed; other
      known risk factors, which were represented to two nominal score points, 0 or 1,
      for patients with and without it, respectively, and TLR2 level, which was treated
      as a metric variable. DM (p=0.002), HT (p=0.001), HL (p<0.001), and TLR2 level
      (p<0.001) were identified as significant contributors for arteriosclerotic
      disease. CONCLUSIONS: High TLR2 expression level on monocytes may be an
      independent risk factor for atherogenesis.

PMID- 19766999
TI  - Association between dyslipidemia and vascular events in patients treated with
      statins: report from the UK General Practice Research Database.
AB  - OBJECTIVE: A retrospective cohort study was conducted to evaluate the association
      between low high-density lipoprotein cholesterol (HDL-C) and/or elevated
      triglycerides (TG) and cardiovascular (CV) and/or cerebrovascular (CB) events
      among patients with elevated low-density lipoprotein cholesterol (LDL-C) despite
      statin treatment. METHODS: Patient demographics, clinical characteristics,
      laboratory data, and CV/CB events, were collected from the UK General Practice
      Research Database. Abnormal lipid levels were defined using US and European
      clinical guidelines. The association between the frequency of CV/CB events among
      patients with HDL-C/TG abnormalities versus patients with isolated low LDL-C was
      estimated using multivariate Cox proportional hazards regression. RESULTS: Of
      19,843 statin-treated patients, 6823 had elevated LDL-C despite therapy for a
      mean follow-up of 1.99+/-1.06 years. Among these patients, 3115 (45.7%) also had
      HDL-C/TG abnormalities. A total of 715 patients (10.5%) experienced CV/CB events.
      In statin-treated patients not at LDL-C goal, the relative risk of a vascular
      event was 24% higher in patients with HDL-C/TG abnormalities (HR=1.24, 95% CI:
      1.06-1.46, p=0.006) than in patients without HDL-C/TG abnormalities. Additional
      variables that were associated with a significantly increased risk of CV/CB
      events included age (p<0.0001), gender (p=0.027), and medication possession ratio
      (p<0.0001), while diabetes mellitus (p<0.0001), hypertension (p<0.0001), 10-year
      Framingham risk score>30% (p=0.005), statin dose (p<0.0001), and LDL-C level at
      baseline (p<0.0001) were associated with a significantly decreased risk of CV/CB
      events. CONCLUSION: Among statin-treated patients with elevated LDL-C from UK
      clinical practices, reduced HDL-C and/or elevated TGs were associated with a
      significantly increased relative risk of CV/CB events.

PMID- 19767000
TI  - Refining and expanding the role of small, dense low-density lipoproteins.

PMID- 19767001
TI  - Independent inverse relationship between serum lycopene concentration and
      arterial stiffness.
AB  - OBJECTIVE: Emerging evidence suggests a role of lycopene in the primary
      prevention of cardiovascular disease. This study aimed to investigate the
      association of serum lycopene concentration with brachial-ankle pulse wave
      velocity (baPWV), a marker of arterial stiffness and markers of oxidative stress
      and inflammation. METHODS: healthy women (n=264, 31-75 yrs) were classified into
      tertiles according to serum lycopene concentration. Multivariate linear
      regression analyses were used to assess the relationship between serum lycopene
      and baPWV. RESULTS: Subjects in middle tertile (T2) and upper tertile (T3) had
      lower baPWV (1263+/-23 and 1265+/-14 cm/s vs. 1338+/-21 cm/s; p=0.009) and lower
      oxidized LDL (oxLDL) (53+/-3 and 55+/-3 U/L vs. 66+/-3 U/L; p<0.001) than those
      in lower tertile (T1). Subjects in T3 showed higher LDL particle size (24.3+/
      0.08 nm vs. 24.0+/-0.07 nm, p=0.005) and lower C-reactive protein (hs-CRP)
      (0.80+/-0.25mg/dL vs. 1.27+/-0.24 mg/dL, p=0.015), compared with those in T1.
      Logistic regression analysis showed that baPWV decreased with the increment of
      lycopene concentration; log baPWV decreased by 0.21 cm/s (95% CI -0.168;-0.045,
      p=0.001) per unit change in lycopene. After adjustment for age, BMI, smoking,
      drinking, menopause and blood pressure, the estimated effect was attenuated by
      35%, but remained statistically significant [-0.13 cm/s (95% CI -0.112;-0.018,
      p=0.006)]. Further adjustment for beta-carotene, alpha-tocopherol, oxLDL, LDL
      particle size, and hs-CRP increased the strength of the association [beta=-0.221
      (95% CI -0.215;-0.012, p=0.029)]. CONCLUSION: This study supports the presence of
      an independent inverse relationship between circulating lycopene and baPWV.
      Additionally, reduced oxidative modification of LDL may be one of mediators on
      the mechanisms how lycopene reduces arterial stiffness.

PMID- 19767002
TI  - Ryanodine receptor 1 mediates Ca2+ transport and influences the biomechanical
      properties in RBCs.
AB  - Ryanodine receptors (RyRs) are a family of Ca2+ channel proteins that mediate the
      massive release of Ca2+ from the endoplasmic reticulum into the cytoplasma. In
      the present study, we manipulated the incorporation of RyR1 into RBC membrane and
      investigated its influences on the intracellular Ca2+ ([Ca2+](in)) level and the
      biomechanical properties in RBCs. The incorporation of RyR1 into RBC membranes
      was demonstrated by both immunofluorescent staining and the change of [Ca2+](in)
      of RBCs. In the presence of RyR1, [Ca2+](in) showed biphasic changes, i.e., it
      increased with the extracellular Ca2+ ([Ca2+](ex)) up to 5muM and then decreased
      with the further increase of [Ca2+](ex). However, [Ca2+](in) remained constant in
      the absence of the RyR1. The results of biomechanical measurements on RBCs,
      including deformability, osmotic fragility, and membrane microviscosity,
      reflected similar biphasic changes of [Ca2+](in) mediated by RyR1 with the
      increases of [Ca2+](ex). Therefore, it is believed that RyR1 can incorporate into
      RBC membrane in vitro, and mediate Ca2+ influx, and then regulate RBC
      biomechanical properties. This information suggests that RBCs may serve as a
      model to study the function of RyR1 as a Ca2+ release channel.

PMID- 19767003
TI  - Determining effective subject-specific strength levels for forward dives using
      computer simulations of recorded performances.
AB  - This study used optimisation procedures in conjunction with an 8-segment torque
      driven computer simulation model of the takeoff phase in springboard diving to
      determine appropriate subject-specific strength parameters for use in the
      simulation of forward dives. Kinematic data were obtained using high-speed video
      recordings of performances of a forward dive pike (101B) and a forward 2 1/2
      somersault pike dive (105B) by an elite diver. Nine parameters for each torque
      generator were taken from dynamometer measurements on an elite gymnast. The
      isometric torque parameter for each torque generator was then varied together
      with torque activation timings until the root mean squared (RMS) percentage
      difference between simulation and performance in terms of joint angles,
      orientation, linear momentum, angular momentum, and duration of springboard
      contact was minimised for each of the two dives. The two sets of isometric torque
      parameters were combined into a single set by choosing the larger value from the
      two sets for each parameter. Simulations using the combined set of isometric
      torque parameters matched the two performances closely with RMS percentage
      differences of 2.6% for 101B and 3.7% for 105B. Maximising the height reached by
      the mass centre during the flight phase for 101B using the combined set of
      isometric parameters and by varying torque generator activation timings during
      takeoff resulted in a credible height increase of 38 mm compared to the matching
      simulation. It is concluded that the procedure is able to determine appropriate
      effective strength levels suitable for use in the optimisation of simulated
      forward rotating dive performances.

PMID- 19767004
TI  - Preparation of novel magnetic cellulose microspheres via cellulose binding domain
      streptavidin linkage and use for mRNA isolation from eukaryotic cells and
      tissues.
AB  - We have developed micron-sized magnetic cellulose microspheres (MCMS),
      biospecifically coated with streptavidin (SA) using a novel cellulose binding
      domain and SA fusion protein, to harvest mRNA from eukaryotic cells and tissues.
      Biospecific connection between SA and MCMS exhibited significant advantages
      compared with traditional chemical coupling, including convenient and simple
      preparation, elimination of toxic compounds, and highly efficient extraction of a
      pure target molecule. To confirm compatibility, mRNA isolated from cell or tissue
      samples was used for amplification of housekeeping genes (GAPDH and beta-actin)
      and specific target genes (two fragments V(H) and V(L) from the variable
      fragments of IgG and the gene encoding GLP-1 receptor). Preliminary studies
      predict that this novel method has potential in future developments in target
      gene isolation and DNA manipulation.

PMID- 19767005
TI  - Hydrodynamic chromatography for the size classification of micron and sub-micron
      sized packing materials.
AB  - Hydrodynamic chromatography (HDC) was used as a size classification and
      purification method for porous bridged ethyl hybrid (BEH) packing materials
      (particles) in the micron to sub-micron range. Using packed column HDC, a batch
      of particles with size 0.76+/-0.26microm was fractionated to yield classified
      material of 1.05+/-0.16microm, reducing the relative standard deviation from 33%
      to 15%. Subsequent chromatographic evaluation of this packing material showed
      significant improvement in column performance and decrease in flow resistance
      over the unclassified material. Comparing a column packed with the classified
      versus non-classified material, the effective flow resistance of the two columns
      was decreased by 58% and the minimum HETP for the packing material was improved
      from 4 to 2.5microm.

PMID- 19767006
TI  - Simultaneous determination of hydrophilic amino acid enantiomers in mammalian
      tissues and physiological fluids applying a fully automated micro-two-dimensional
      high-performance liquid chromatographic concept.
AB  - A validated two-dimensional HPLC system combining a microbore-monolithic ODS
      column and a narrowbore-enantioselective column has been established for a
      sensitive and simultaneous analysis of hydrophilic amino acid enantiomers (His,
      Asn, Ser, Gln, Arg, Asp, allo-Thr, Glu and Thr) and the non-chiral amino acid,
      Gly, in biological samples. To accomplish this goal, the amino acids were first
      tagged with 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F) to the respective
      fluorescent NBD derivatives which were separated in the first dimension by a
      micro-reversed-phase column. The automatically collected fractions of the target
      peaks were then transferred to the second dimension consisting of a Pirkle type
      enantioselective column generating separation factors higher than 1.13 for all
      the enantiomeric target analytes. The system was validated using standard amino
      acids and a rat plasma sample, and analytically satisfactory calibration and
      precision results were obtained. The present 2D-HPLC system enables the fully
      automated determination of hydrophilic amino acid enantiomers in mammalian
      samples. The d-isomers of all the investigated 9 amino acids were found in rat
      urine but at various enantiomeric ratios.

PMID- 19767007
TI  - Effects of pressure drop, particle size and thermal conditions on retention and
      efficiency in supercritical fluid chromatography.
AB  - The effects of particle size and thermal insulation on retention and efficiency
      in packed-column supercritical fluid chromatography with large pressure drops are
      described for the separation of a series of model n-alkane solutes. The columns
      were 2.0mm i.d.x150mm long and were packed with 3, 5, or 10-mum porous
      octylsilica particles. Separations were performed with pure carbon dioxide at 50
      degrees C at average mobile phase densities of 0.47g/mL (107bar) and 0.70g/mL
      (151bar). The three principal causes of band broadening were the normal
      dispersion processes described by the van Deemter equation, changes in the
      retention factor due to the axial density gradient, and radial temperature
      gradients associated with expansion of the mobile phase. At the lower density the
      use of thermal insulation resulted in significant improvements in efficiency and
      decreased retention times at large pressure drops. The effects are attributed to
      the elimination of radial temperature gradients and the concurrent enhancement of
      the axial temperature gradient. Thermal insulation had no significant effect on
      chromatographic performance at the higher density. A simple expression to predict
      the onset of excess efficiency loss due to the radial temperature gradient is
      proposed.

PMID- 19767008
TI  - Characterization of an aluminium(III)-citrate species by means of ion
      chromatography with inductively coupled plasma-atomic emission spectrometry
      detection.
AB  - The aluminium(III)-citrate complex
      (NH(4))(4)[Al(2)(C(6)H(4)O(7))(C(6)H(5)O(7))(2)].4H(2)O was characterized using
      anion exchange chromatography on-line coupled with the element specific ICP-AES
      detector. Time-dependent monitoring of individual species in aqueous solution at
      different temperatures gave information about the species stability and the
      decomposition pathway. The aluminium-citrate complex
      (NH(4))(4)[Al(2)(C(6)H(4)O(7))(C(6)H(5)O(7))(2)].4H(2)O disintegrated via an
      unknown intermediary Al(III)-citrate species from which the thermodynamically
      stable complex [Al(3)(C(6)H(4)O(7))(3)(OH)(H(2)O)](4-) was formed. The activation
      energy for the decomposition reaction and the pre-exponential factor were
      determinated to be E(a)=81.95kJmol(-1) and A=3.62x10(13)s(-1).

PMID- 19767009
TI  - Simplified kinetic calibration of solid-phase microextraction for in vivo
      pharmacokinetics.
AB  - Solid-phase microextraction (SPME) has been demonstrated to be useful for in vivo
      sampling in pharmacokinetic studies. In this study, a single time-point kinetic
      calibration for in vivo dynamic monitoring was developed by simplification of the
      laborious multiple time-point kinetic calibration, based on the independent
      desorption kinetics of the preloaded standards from SPME fibers with the changing
      analyte concentrations. The theoretical foundation and practical application
      conditions, such as the replicate numbers, the optimal time-point for desorption,
      and the sampling time, were systematically investigated. Furthermore, the
      feasibility of using regular standards rather than deuterated ones for the
      kinetic calibration was justified by comparing to the data obtained using the
      deuterated standards. All the methods were verified by in vitro and in vivo
      experiments. The results from in vivo SPME were validated by the blood drawing
      and chemical assay. These simplified calibration methods improved the
      quantitative applications of SPME for dynamic monitoring and in vivo sampling,
      enhance the multiplexing capability and automatic potentials for high throughput
      analysis, and decrease expenses on reagents and instruments.

PMID- 19767010
TI  - Development of an enzymatic microreactor based on microencapsulated laccase with
      off-line capillary electrophoresis for measurement of oxidation reactions.
AB  - Microencapsulation is used here as a new technique to immobilize enzymes in a
      microreactor coupled off-line to capillary electrophoresis (CE), allowing the
      determination of enzymatic reaction products. The redox enzyme laccase was
      encapsulated using the method of interfacial cross-linking of poly(ethyleneimine)
      (PEI). The 50 microm diameter capsules were slurry packed from a suspension into
      a capillary-sized reactor made easily and quickly from a short length of 530
      microm diameter fused-silica tubing. The volume of the bed of laccase
      microcapsules in the microreactor was in the order of 1.1 microL through which 50
      microL of the substrate o-phenylenediamine (OPD) was flowed. The oxidation
      product 2,3-diaminophenazine (DAP) and the remaining OPD were quantified by CE in
      a pH 2.5 phosphate buffer. Peak migration time reproducibility was in the order
      of 0.4% RSD and peak area reproducibility was less than 1.7% RSD within the same
      day. Using the OPD peak area calibration curve, a conversion efficiency of 48%
      was achieved for a 2-min oxidation reaction in the microreactor.

PMID- 19767011
TI  - A Tucker model based approach for analysis of complex oil biodegradation data.
AB  - A novel method based on gas chromatography-mass spectrometry in selected ion
      monitoring mode (GC-MS/SIM) and Tucker models is developed to evaluate the
      effects of oil type, microbial treatments and incubation time on the
      biodegradation of petroleum hydrocarbons. The data set consists of sections of
      the m/z 180, 192 and 198 GC-MS/SIM chromatograms of oil extracts from a
      biodegradation experiment where four oil types were exposed to four microbial
      treatments over a period of one year. The chosen sections, which are specific to
      methylfluorenes, phenanthrenes and dibenzothiophenes, were combined in a 4-way
      array (incubation timexoil typextreatmentxcombined chromatographic retention
      times) that was analyzed using both principal component analysis and the Tucker
      model. Several conclusions could be reached: the light fuel oil was the least
      degradable of those tested, 2- and 3-methyl isomers were more easily degraded
      compared to the 4-methyl isomers, the mixture of surfactant producers and PAC
      degraders provided the most effective degradation and the largest part of the
      degradation occurred between 54 and 132 days.

PMID- 19767012
TI  - An experimental test of the effects of gender constancy on sex typing.
AB  - This study provides an experimental test of the hypothesis that level of gender
      constancy understanding affects children's sex typing. Preschool-age children
      (N=62, mean age=47 months) were randomly assigned to experimental lessons that
      taught that biological traits (including gender) are either fixed (pro-constancy
      condition) or mutable (anti-constancy condition). Posttests revealed that the
      lessons were effective; children in the pro-constancy condition showed higher
      gender constancy and appearance-reality distinction scores than did children in
      the anti-constancy condition. Sex typing did not, however, differ between
      treatment conditions at immediate and 3-month posttesting.

PMID- 19767013
TI  - Inverse relationship between numbers of 5-HT transporter binding sites and life
      history of aggression and intermittent explosive disorder.
AB  - The objective of this study was to determine if platelet 5-HT transporter (5-HTT)
      sites vary as a function of aggression, and/or impulsiveness, and differ as a
      function of Intermittent Explosive Disorder (IED). Accordingly, the number of
      platelet 5-HTT sites was assessed in 100 personality disordered (PD) individuals
      with varying degrees of aggressiveness. The number of platelet 5-HTT sites was
      assessed by examining the Bmax of H(3)-Paroxetine Binding to the blood platelet.
      Life history of aggression was assessed by Life History of Aggression.
      Impulsivity was assessed by the Barratt Impulsiveness Scale. Diagnoses of IED
      were made by both DSM-IV and Research Criteria. Examination of the data revealed
      that Bmax, but not Kd, values of Platelet H(3)-Paroxetine Binding correlated
      inversely with the LHA Aggression score (r=-.42 n=87, p<.001) but not with the
      BIS-11 Impulsivity score (r=.03, n=77, p=.777). PD subjects meeting Research
      Criteria for IED demonstrated a significant reduction in Bmax values for Platelet
      H(3)-Paroxetine Binding. These results were similar after accounting for the
      effect of lifetime history of depressive mood disorder on Bmax values for
      Platelet H(3)-Paroxetine Binding. These data indicate a significant inverse
      relationship between platelet 5-HTT and aggression, though not impulsivity, as a
      dimensional variable in personality disordered individuals. Results from the
      examination of IED as a categorical aggression variable suggest that Research,
      rather than DSM-IV, criteria better identify individuals with reduced numbers of
      platelet 5-HTT sites.

PMID- 19767014
TI  - Brain lipid concentrations in bipolar disorder.
AB  - Reduced concentrations of docosahexaenoic acid (DHA, 22:6n-3) and arachidonic
      acid (AA, 20:4n-6) have been reported in the postmortem bipolar disorder (BD)
      brain. Additionally, an increased prevalence of BD has been related to low
      dietary intake of fish, and dietary supplements containing fish products or DHA
      have been reported to ameliorate BD symptoms. These observations suggest that
      brain lipid metabolism, particularly involving DHA, is disturbed in BD. To test
      this suggestion, concentrations of different lipids were measured using internal
      standards in postmortem frontal cortex from eight BD patients and six matched
      controls. Compared with control cortex, the BD cortex showed no statistically
      significant difference in mean concentrations (per gram wet weight) of "stable"
      lipids (total lipid, total phospholipid, individual phospholipids, or
      cholesterol), of unesterified fatty acids, or of esterified DHA or AA within
      stable lipids. Fractional esterified AA and DHA concentrations also did not
      differ significantly between groups. Some fatty acid concentration differences
      were found in low-abundant cholesteryl ester. These results do not support the
      hypothesis of disturbed brain lipid concentrations, including concentrations of
      AA and DHA, in BD. Positron emission tomography might be used, however, to see if
      brain AA or DHA kinetics are disturbed in the disease.

PMID- 19767015
TI  - Altered gene expression of histone deacetylases in mood disorder patients.
AB  - Chromatin remodeling such as changes in histone acetylation has been suggested to
      play an important role in the pathophysiology and treatment of mood disorders. In
      the present study, we investigated whether the expression of histone deacetylase
      (HDAC) genes are altered in mood disorder patients. We used quantitative real
      time PCR to measure the mRNA levels of 11 HDACs (HDAC1-11) in peripheral white
      blood cells of major depressive disorder (MDD) and bipolar disorder (BPD)
      patients during depressive and remissive episodes and in the first-degree
      relatives of BPD patients. In addition, we investigated the effect of
      antidepressants and mood stabilizers on the mRNA levels of HDACs using mice. In
      MDD, the expression of HDAC2 and -5 mRNA was increased in a depressive state, but
      not in a remissive state, compared to controls. In BPD, the expression of HDAC4
      mRNA was increased only in a depressive state, and the expression of HDAC6 and -8
      was decreased in both depressive and remissive states compared to controls,
      whereas the first-degree relatives did not show any significant alteration in
      expression levels. Animal study showed that the expression of HDAC2 and -5 or
      HDAC4, -6 and -8 mRNAs in the mouse leukocytes were not affected by chronic
      treatment with antidepressants or mood stabilizers. Our data suggest that
      aberrant transcriptional regulation caused by the altered expression of HDACs is
      associated with the pathophysiology of mood disorders.

PMID- 19767016
TI  - Relationship between neuropsychological outcome and DBS surgical trajectory and
      electrode location.
AB  - BACKGROUND: The outcome literature of subthalamic nuclei (STN) deep brain
      stimulation (DBS) suggests that cognitive declines are commonly reported
      following surgery. We hypothesized that differences in electrode position and
      surgical trajectory may lead to a differential neuropsychological outcome.
      METHODS: We conducted a standardized evaluation of the location of the DBS
      electrode tip and the active electrodes, the surgical trajectory through which
      they were placed, and their relation to neuropsychological change scores (mental
      status, verbal memory, verbal fluency, and psychological measures) in 17
      bilateral STN DBS patients using 6 months post-surgical magnetic resonance
      imaging data. RESULTS: Declines in mental status scores were related to
      electrodes that were more posterior-laterally placed within the frontal quadrant
      in either hemisphere or those located superiorally in the left hemisphere.
      Electrodes that were closer to the approximated STN and more superiorally located
      in the left hemisphere were associated with verbal learning declines at 6 months
      following surgery. In the right hemisphere, the electrodes that were located more
      in the lateral direction were related to verbal short-term memory declines; while
      for verbal long-term memory declines were found for electrodes located more
      posterior-laterally in the left hemisphere. Declines in verbal fluency scores
      were more variable with associations found between change scores and electrodes
      in the lateral and superior directions in the left hemisphere and those
      electrodes closer to the approximated STN and more superiorally and posteriorally
      located in the right hemisphere. In contrast, semantic fluency declines were only
      related to right hemisphere electrodes located more superiorally. Declines in
      mood were related to those electrodes located further away from the approximated
      STN, particularly those located more inferiorally and laterally in the left
      hemisphere. Anxiety change scores were not associated with the location of the
      electrodes. CONCLUSIONS: The results provide preliminary evidence that 6 months
      following bilateral STN DBS cognitive and emotional changes may be related to the
      surgical trajectory and electrode placement.

PMID- 19767017
TI  - Homograft aortic root replacement in native or prosthetic active infective
      endocarditis: twenty-year single-center experience.
AB  - OBJECTIVE: We compared early and long-term results of cryopreserved homograft
      aortic root replacement in native valve endocarditis or prosthetic valve
      endocarditis associated with periannular abscess. METHODS: Between May 1986 and
      December 2007, 1163 patients with endocarditis were operated upon. Of these, 221
      patients (n = 185 men, median age 55 years) had homograft aortic root replacement
      due to 99 cases of native valve endocarditis (45%) and 122 of prosthetic valve
      endocarditis (55%). Perinannular abscess developed in 189 patients (86%), and
      aortoventricular dehiscence in 120 (63.5%) of them. Perioperative
      characteristics, probability of survival, freedom from recurrence, and
      reoperation were analyzed. Follow-up (mean 5.2 +/- 0.4 years, maximum 18.4 years)
      was completed in 96.8% with a total of 1127 patient-years. RESULTS: Overall
      native valve endocarditis survival at 30 days and 1, 5, and 10 years was 83.8% +/
      3.7%, 76.6% +/- 4.3%, 66.5% +/- 4.9%, and 47.3% +/- 5.6%, respectively,
      significantly better than for patients with prosthetic valve endocarditis, who
      had a greater tendency toward abscess formation (P = .029). Thirty-one patients
      (14.0%) required reoperation either for structural valve deterioration (n = 19,
      8.6%), with a greater tendency in patients aged <40 years, or for recurrent
      endocarditis of the homograft (n = 12, 5.4%). One-year reoperation mortality rate
      was 16.1% (n = 5). CONCLUSIONS: Homograft aortic root replacement in active
      infective endocarditis with periannular abscess formation shows satisfactory
      early and long-term results with significantly better survival in native valve
      endocarditis than prosthetic valve endocarditis. It is associated with a low
      recurrence rate, although the risk of structural valve deterioration increases
      over time, especially in young patients, and reoperation remains a challenge. In
      our institution, the homograft remains the preferred valve substitute in active
      infective endocarditis with periannular abscess formation.

PMID- 19767018
TI  - Ecological impacts of tributyltin on estuarine communities in the Hastings River,
      NSW Australia.
AB  - Oyster (Saccostrea commercialis) biomonitoring, assessment of oyster and
      gastropod (Bembicium auratum) abundance, and gastropod imposex were used to
      measure the significance of tributyltin (TBT) contamination in an intertidal
      mangrove forest. We studied the bioavailable levels of TBT in oysters
      approximately 1 km downstream and 2 km upstream from a TBT waste disposal site.
      We found observable declines in the abundance of oysters and gastropods
      correlated with the bioavailable TBT and these findings were confirmed by mapping
      oyster beds. Oyster cover near the disposal site ranged from 0% to 5% while
      downstream and upstream populations ranged in cover from 25-50% to 5-25%,
      respectively. Similarly, gastropod abundances at the disposal site were only 7%
      of the downstream population and 17% of the upstream population. Imposex was
      present in 90% of female B. auratum from populations near the disposal site but
      this effect declined more sharply than the population level effects.

PMID- 19767019
TI  - Riverine input of particulate material and inorganic nutrients to a coastal reef
      ecosystem at the Caribbean coast of Costa Rica.

PMID- 19767020
TI  - Seabirds as indicators of aquatic ecosystem conditions: a case for gathering
      multiple proxies of seabird health.
AB  - The use of seabirds as sentinels of the condition of aquatic ecosystems has been
      well-established. Large environmental perturbations to aquatic food webs (e.g.,
      chemical contamination, overfishing, particulate pollution) have all been
      detected or monitored by tracking seabirds at colonies. However, seabirds may
      elicit more subtle, sublethal responses that can also be used to track ecosystem
      health, or the health of seabird populations. In this article, we advocate for
      field researchers to plan a priori to collect a broader suite of samples when
      handling seabirds, and to reach out for collaboration with specialists (e.g.,
      parasitologists, wildlife veterinarians). Collectively, such efforts will greatly
      improve our ability to establish baseline physiological and chemical levels for
      seabirds, against which we can detect future changes in aquatic ecosystems.

PMID- 19767021
TI  - [Facial edema due to gemfibrozil].

PMID- 19767023
TI  - [Screening tools for malnutrition in hospitalized patients].

PMID- 19767024
TI  - [Metformin and vitamin B12 deficiency].

PMID- 19767025
TI  - [Prognosis of patients receiving continuous renal replacement therapy in an
      intensive care unit].

PMID- 19767026
TI  - [Medical consultation: problems and solutions].

PMID- 19767027
TI  - [Kaposi's sarcoma].

PMID- 19767028
TI  - [Technology, social requirement, and "wish-fulfilling medicine"].

PMID- 19767029
TI  - [Age-related macular degeneration: analysis of the results of ranibizumab
      therapy].

PMID- 19767030
TI  - [Liver metastases of pancreatic endocrine carcinoma].

PMID- 19767031
TI  - [Hypopigmented mycosis fungoides].

PMID- 19767032
TI  - [Clinical guidelines for prophylaxis of venous thromboembolism in the elderly].

PMID- 19767033
TI  - [Rare diseases, an emergent paradigm in the medicine of the XXI century].

PMID- 19767034
TI  - [Clinicopathological characteristics and survival outcome of esophageal cancer.
      Results from a series of 200 patients].
AB  - BACKGROUND AND OBJECTIVE: The esophageal cancer (EC) is a slightly frequent but
      serious disease. Our aim is to describe the characteristics of the patients with
      EC in our Hospital. PATIENTS AND METHOD: We included 200 patients consecutively
      diagnosed and/or treated for CE between between January, 2003 and December, 2007.
      The location of the tumor was analyzed, the histological type, the proofs
      realized for to establish the classification, the treatments, the survival and
      the morbi-mortality of the surgery. RESULTS: The endoscopic ultrasonography (EUS)
      modified the therapeutic strategy in 12% of the patients. The survival to the
      year, 3 years and 5 years was 48%, 25% and 21%, respectively. 74 (32%) patients
      were operated, 48 (65%) of them was treated with neoadjuvant chemoradiotherapy.
      The postsurgical mortality was 8% (6 patients) and the morbidity was 57% (114
      patients). In multivariate analysis, after adjustment for traditional risk
      factors, were the location in the average third ( [HR, hazard ratio]=2.3;
      confidence interval [IC] of 95%, 1.3-4.1) and not accomplishment of surgery after
      the chemotherapy and radiotherapy (HR=1.9; IC to 95%, 1.15-3). CONCLUSIONS: The
      diagnosis is realized very later. The EUS has contributed a better therapeutic
      strategy to our patients. The mortality continues being high.

PMID- 19767035
TI  - [Coexistence of antitopoisomerase I and anticentromere antibodies in systemic
      sclerosis].

PMID- 19767036
TI  - [Eight-and-a-half syndrome].

PMID- 19767037
TI  - [Syringomyelia shoulder neuroarthropathy].

PMID- 19767038
TI  - Berberine improves free-fatty-acid-induced insulin resistance in L6 myotubes
      through inhibiting peroxisome proliferator-activated receptor gamma and fatty
      acid transferase expressions.
AB  - The plant alkaloid berberine (BBR) has been reported to have antidiabetic effect
      in humans and animals. However, the mechanism of action is not well understood.
      The present study was conducted to determine the effect and mechanism of action
      of BBR on the free-fatty-acid (FFA)-induced insulin resistance in muscle cells.
      The FFA-induced insulin-resistant cell model was established in L6 myotubes by
      treating them with 250 mumol/L of palmitic acid. The inclusion of FFA in the
      medium increased peroxisome proliferator-activated receptor gamma (PPARgamma) and
      fatty acid transferase (FAT/CD36) expressions by 26% and 50% and decreased
      glucose consumption by 43% and insulin-mediated glucose uptake by 63%,
      respectively. Berberine treatment increased the glucose consumption and insulin
      stimulated glucose uptake in normal cells and improved glucose uptake in the FFA
      induced insulin-resistant cells. The improved glucose uptake by BBR was
      accompanied with a dose-dependent decrease in PPARgamma and FAT/CD36 protein
      expressions. In insulin-resistant myotubes, BBR (5 micromol/L) decreased
      PPARgamma and FAT/CD36 proteins by 31% and 24%, whereas PPARgamma antagonist
      GW9662 reduced both proteins by 56% and 46%, respectively. In contrast, PPARgamma
      agonist rosiglitazone increased the expression of PPARgamma and FAT/CD36 by 34%
      and 21%, respectively. Our results suggest that BBR improves the FFA-induced
      insulin resistance in myotubes through inhibiting fatty acid uptake at least in
      part by reducing PPARgamma and FAT/CD36 expressions.

PMID- 19767039
TI  - Comparative characterization of the Arabidopsis subfamily a1 beta-galactosidases.
AB  - The Arabidopsis genome contains 17 predicted beta-galactosidase genes, all of
      which belong to glycosyl hydrolase (GH) Family 35. These genes have been further
      grouped into seven subfamilies based on sequence similarity. The largest of
      these, subfamily a1, consists of six genes, Gal-1 (At3g13750), Gal-2 (At3g52840),
      Gal-3 (At4g36360), Gal-4 (At5g56870), Gal-5 (At1g45130), and Gal-12 (At4g26140),
      some of which were characterized in previous studies. We report here the
      purification and biochemical characterization of recombinant Gal-1, Gal-3, Gal-4
      and Gal-12 from Pichiapastoris, completing the analysis of all six recombinant
      proteins, as well as the isolation and characterization of the native Gal-2
      protein from Arabidopsis leaves. Comparison of the relative expression levels of
      the subfamily a1 beta-galactosidases at the mRNA and protein levels uncovered
      evidence of differential regulation, which may involve post-transcriptional and
      post-translational processes. In addition, this study provides further support
      for the proposed function of the subfamily a1 beta-galactosidases in cell wall
      modification based on analysis of the organ-specific expression and subcellular
      localization of Gal-1 and Gal-12. Our study suggests that, despite some
      differences in individual biochemical characteristics and expression patterns,
      each member of the family has the potential to contribute to the dynamics of the
      Arabidopsis plant cell wall.

PMID- 19767040
TI  - Lipoxygenases - Structure and reaction mechanism.
AB  - Lipid oxidation is a common metabolic reaction in all biological systems,
      appearing in developmentally regulated processes and as response to abiotic and
      biotic stresses. Products derived from lipid oxidation processes are collectively
      named oxylipins. Initial lipid oxidation may either occur by chemical reactions
      or is derived from the action of enzymes. In plants this reaction is mainly
      catalyzed by lipoxygenase (LOXs) enzymes and during recent years analysis of
      different plant LOXs revealed insights into their enzyme mechanism. This review
      aims at giving an overview of concepts explaining the catalytic mechanism of LOXs
      as well as the different regio- and stereo-specificities of these enzymes.

PMID- 19767041
TI  - 'Learn the signs. Act early': a campaign to help every child reach his or her
      full potential.
AB  - OBJECTIVE: To examine the application of a social marketing approach to increase
      the early identification and treatment of autism and other developmental
      disorders. STUDY DESIGN: The intervention used formative research, behaviour
      change theory and traditional social marketing techniques to develop a campaign
      targeting parents, healthcare professionals and early educators to increase
      awareness of autism and other developmental delays, and to prompt action if a
      developmental delay was suspected. METHOD: Using social marketing principles, the
      Centers for Disease Control and Prevention applied baseline research with the
      target audiences to understand the barriers and motivators to behaviour change,
      which included a lack of knowledge and resources (barriers), along with a
      willingness to learn and do more (motivators). Focus group testing of potential
      campaign concepts led to one particular approach and accompanying images, which
      together increased perceived severity of the problem and encouraged taking
      action. The audience research also helped to shape the marketing mix (product,
      price, place and promotion). RESULTS: Three-year follow-up research in this case
      study indicates a significant change in parent target behaviours, particularly
      among parents aware of the campaign, and substantially more healthcare
      professionals believe that they have the resources to educate parents about
      monitoring their child's cognitive, social and physical development. Qualitative
      results from early educators and childcare professional associations have been
      positive about products developed for daycare settings. CONCLUSION: The
      application of social marketing principles, behavior change theory and audience
      research was an effective approach to changing behaviours in this case.
      Understanding what the target audiences want and need, looking beyond parents to
      engage healthcare professionals and early educators, and engaging many strategic
      partners to extend the reach of the message helped campaign planners to develop a
      campaign that resonated with the target audiences and, importantly, moved them
      towards action.

PMID- 19767042
TI  - Localization of porcine reproductive and respiratory syndrome virus in mammary
      glands of experimentally infected sows.
AB  - We investigated the localization of porcine reproductive and respiratory syndrome
      virus (PRRSV) in the mammary glands of experimentally infected sows using reverse
      transcription PCR and immunohistochemistry. Six pregnant sows were inoculated
      intranasally with PRRSV three weeks prior to the predicted farrowing date. The
      six PRRSV-infected sows and two uninfected negative control sows remained
      clinically healthy and farrowed normally. Milk samples were collected from all
      sows on lactation days 1, 2, and 3. PRRSV was detected in milk as early as
      lactation day 1 in all of the PRRSV-infected sows, but not in the uninfected
      sows. PRRSV antigen was detected by immunohistochemistry in macrophage-like cells
      in the alveolar lumina of the mammary glands and in other tissues. Our results
      show that PRRSV is shed in the milk of infected sows, and that PRRSV antigen is
      present in the mammary glands of experimentally infected sows.

PMID- 19767043
TI  - Postoperative intra-abdominal infection increases angiogenesis and tumor
      recurrence after surgical excision of colon cancer in mice.
AB  - BACKGROUND: Recent reports have suggested that anastomotic leakage is associated
      with greater rates of tumor recurrence and cancer-specific mortality after
      surgery for colorectal cancer. The impact of postoperative intra-abdominal
      infection on long-term oncologic results, however, is still controversial, and no
      direct causal relationship has been found between both processes. Our aim was to
      investigate the influence of postoperative intraabdominal infection on
      angiogenesis and tumor growth in an animal model of colon cancer. METHODS: Balb/c
      mice were randomized immediately after injection of 5x10(6) B51LiM cells into the
      cecal wall into 2 groups: cecal resection without postoperative infection (group
      1), and cecal resection with postoperative intra-abdominal infection (group 2). A
      total of 18 days after cell injection, cecectomy was performed, and infection was
      induced in group 2 by intraperitoneal injection of 3x10(8) colony-forming units
      of Bacteroides fragilis. On postoperative day 12, the mice were killed. RESULTS:
      Comparing group 1 with group 2, tumor recurrence was more frequent in animals
      with intraabdominal infection (65% vs 100%, respectively; P=02). VEGF serum
      levels were greater at the time of sacrifice in the group with infection (11+/-10
      vs 30+/-23 pg/mL; P<.05). Tumor angiogenesis was also increased in the
      postoperative infection group. The mean (+/-standard deviation) microvessel
      density was 16+/-7 versus 28+/-11 vessels per high-power field (P<.05).
      CONCLUSION: We concluded that postoperative intra-abdominal infection increases
      angiogenesis and tumor recurrence after operative excision of a colon cancer in
      mice.

PMID- 19767044
TI  - A name, a name, what's in a name?

PMID- 19767045
TI  - Long-term follow-up of patients with incidentally discovered pancreatic cystic
      neoplasms evaluated by endoscopic ultrasound.
AB  - BACKGROUND: The management of incidental pancreatic cysts is not well established
      because of lack of information on their natural history. International Consensus
      Guidelines advocate observation of asymptomatic patients with small lesions,
      despite limited data to support this approach. METHODS: To characterize clinical
      outcomes in a cohort of asymptomatic patients with incidental pancreatic cysts
      who underwent endoscopic ultrasound (EUS) evaluation+/-fine needle aspiration
      (FNA). RESULTS: Overall, 317 patients underwent EUS for evaluation of pancreatic
      cysts from 1995 to 2005. A total of 97/317 (31%) had asymptomatic, incidentally
      discovered pancreatic cysts; of 97 asymptomatic patients, 93 were contacted. Of
      these patients, 71/93 (76%) had lesions<3 cm and benign EUS features. All were
      followed without operative therapy. The mean follow-up was 44 months (range, 6
      123). A total of 69/71 (97%) were alive and free of symptoms of pancreatic
      disease; 2 patients died of unrelated causes. Among these 71 patients with
      lesions<3 cm, FNA was performed in 33 patients and cytology was negative for
      malignant cells in all. Overall, 45/71 patients had either follow-up cross
      sectional imaging or EUS. All of them had stable lesions. Surveillance studies
      were performed with a mean follow-up of 28 months (range, 4-120). The 22 patients
      with lesions >3 cm and/or concerning EUS features underwent resection. Pathologic
      analysis revealed that 2/22 patients had adenocarcinoma and that 60% had
      premalignant lesions. CONCLUSION: Endoscopic ultrasound is helpful in evaluation
      of patients with small incidental pancreatic cystic lesions. Asymptomatic cysts
      with benign radiographic and/or endosonographic features may safely be followed
      clinically and with serial imaging.

PMID- 19767046
TI  - Gastric volvulus as a complication in the recipients after adult living donor
      liver transplantation.
AB  - BACKGROUND: We report 4 adult cases of mesenteroaxial gastric volvulus after
      living donor liver transplantation (LDLT). RESULTS: All 4 recipients were female
      with a median age of 31 years (range, 21-69). All had undergone right lobe LDLT.
      Gastric volvulus developed on postoperative days (POD) 4-30, and all were
      successfully treated with an endoscopic correction procedure. Two of 4 needed a
      repeated correction procedure and 1 needed a surgical revision for the recurrent
      volvulus. CONCLUSION: Although this type of the complication is unusual, earlier
      post-transplant endoscopic intervention is useful to reverse the pyloroantral
      obstruction. These cases let us recognize that gastric volvulus is one of the
      complications after right lobe LDLT.

PMID- 19767047
TI  - Contribution of biologically derived nanoparticles to disease.

PMID- 19767048
TI  - Clinical value of additional resection of a margin-positive proximal bile duct in
      hilar cholangiocarcinoma.
AB  - BACKGROUND: Based on frozen section examination, additional resection of the
      proximal bile duct was performed to achieve a negative margin at the time of
      resection of hilar cholangiocarcinoma. The aim of this study was to determine
      whether additional resection of a margin-positive proximal duct can improve
      survival. METHODS: The records of 303 resected patients with hilar
      cholangiocarcinoma were reviewed, focusing on the status of the proximal ductal
      margin. RESULTS: Frozen section examination of the proximal ductal margin was
      carried out in 138 of the 303 patients included in this study. The
      histopathologic diagnosis was negative in 110 patients, positive with carcinoma
      in situ in 11, and positive with invasive cancer in 17. In the 17 patients with
      invasive cancer, additional resection was performed in 12. The length of
      resection was <or=5 mm in all patients. With additional resection, a negative
      margin was achieved in 8 patients. The survival rate for patients in whom a
      negative margin was achieved after additional resection (n=8) was worse than that
      for patients with a negative margin or a positive with carcinoma in situ margin
      (n=275) and was similar to that for patients with a positive margin with invasive
      cancer (n=20). CONCLUSION: Additional resection of >5 mm in the proximal duct is
      difficult after maximal or near-maximal resection of the duct. Such limited
      resection of a margin-positive proximal duct does not improve survival, even when
      a negative margin can be achieved with additional resection.

PMID- 19767049
TI  - Response to "cancer care in the pediatric surgical patient: a paradigm to abolish
      volume-outcome disparities in surgery".

PMID- 19767050
TI  - Surgical research publication in a selection of research and surgical specialty
      journals.
AB  - BACKGROUND: A prior study revealed a paucity of surgical research in the 5 top
      rated general surgery journals for 1998. The hypothesis of the current study was
      that a large amount of surgical research was published in other journals.
      METHODS: In all, 15 research journals and 9 surgery specialty journals were
      reviewed for basic research, funded clinical studies, randomized clinical trials,
      and drug trials. The funding sources and the surgeon's role were recorded. The
      findings were compared with research published in the previously studied 5
      journals in 1998 and 2005. RESULTS: Of 6,016 papers in the research and surgery
      specialty journals, 19% were research, of which 76% were basic research. Funding
      from 1,101 sources was provided to 825 studies (70%). Seventy-four percent of
      funded studies were basic research. Government was the source for 46% of grants,
      private for 41%, and industry for 13%. A surgeon was the sole or senior author in
      72% of studies. A total of 1,172 research articles were published in the research
      and surgery specialty journals in 1998. In comparison, 369 research papers were
      published in the general surgery journals in 1998 and 306 papers were published
      in 2005. With respect to the type of research, there were 896 basic research
      papers in the research and specialty journals in 1998, 200 such papers in the
      general surgery journals in 1998, and 164 in 2005. There were 87 randomized
      trials in the research and the surgery specialty journals in 1998, 46 such papers
      in the general surgery journals in 1998, and 29 in 2005. CONCLUSION: A 3-fold
      greater volume of surgical research and more than a 4-fold greater volume of
      basic research was found in the research and the surgical specialty journals than
      in the general surgical journals in 1998, and this margin is increased when
      compared with the data for 2005. Consideration of only the general surgical
      journals greatly underestimates the surgical research being conducted.

PMID- 19767052
TI  - Diagnosis of gastrointestinal anastomotic dehiscence after hospital discharge:
      Impact on patient management and outcome.
AB  - BACKGROUND: Anastomotic leaks are inevitable complications of gastrointestinal
      surgery. Early hospital discharge protocols have increased concern regarding
      outpatient presentation with anastomotic leaks. METHODS: One hundred anastomotic
      leaks in 5,387 intestinal operations performed at a single institution from 2002
      to 2007 were identified from a prospectively maintained database. Statistical
      analysis was conducted by the unpaired t test, Chi-square test, and analysis of
      variance. RESULTS: Overall anastomotic leak with a rate of 2.6% for colonic and
      0.53% for small bowel anastomoses. Mean time to anastomotic leak diagnosis was 7
      days after operation. Twenty-six patients presented after discharge, with mean
      time to diagnosis 12 days versus 6 days for inpatients (P<.05). Patients
      presenting after hospital discharge were younger, had lesser American Society of
      Anesthesiologists (ASA) scores, and were more likely to have colon cancer and
      less likely to have Crohn's disease. Ninety-two patients required operative
      management, of whom 81 (90%) underwent diversion. No difference in management,
      intensive care unit (ICU) requirement, duration of stay, or mortality between
      inpatient versus outpatient diagnosis was demonstrated. Follow-up at mean of 36
      months demonstrated no difference in readmission, reoperation, or mortality rate
      between outpatient and inpatient diagnosis. Restoration of gastrointestinal
      continuity was achieved in 61-67% in the outpatient and 59% in the inpatient
      group (P=NS). CONCLUSION: Outpatient presentation delays diagnosis but does not
      alter management or clinical outcome, or decrease the probability of ostomy
      reversal. Prolonging hospital stay to capture patients who develop anastomotic
      leak seems to be unwarranted. For patients requiring operative management, we
      recommend diversion as the safest option with a subsequent 61% reversal rate.

PMID- 19767053
TI  - Resonant-ultrasound spectroscopy for studying annealing effect on elastic
      constant of thin film.
AB  - In this paper, we study the elastic property of thin films using resonant
      ultrasound spectroscopy (RUS). RUS determines the elastic constants of a solid
      from its resonance frequencies of free vibration. There were two problems to be
      solved for applying RUS to thin films: accurate measurement of the resonance
      frequencies and mode identification of each resonance frequency. We solve these
      problems using the tripod needle transducers and the laser-Doppler interferometry
      (LDI). In this paper, we describe the RUS/LDI measurement setup we developed, and
      show the relationship between the elastic constant and annealing temperature for
      Cu thin films. Then, we discuss the effects of recrystallization and recovery on
      the elastic constant referring the X-ray diffraction measurement.

PMID- 19767051
TI  - Decreased collagen and increased matrix metalloproteinase-13 in experimental
      abdominal aortic aneurysms in males compared with females.
AB  - BACKGROUND: This study examined differences in sex in collagen regulation during
      rodent experimental abdominal aortic aneurysm formation. METHODS: Infrarenal
      aortas of male and female rats were perfused with elastase or saline (control).
      Aortic diameters were measured at baseline (day 0) and on postoperative days 7
      and 14. Transforming growth factor-beta 1, collagen subtypes I and III, and
      matrix metalloproteinase-13 (MMP-13; collagenase-3) expression and/or protein
      levels from aortic tissue were determined by real-time reverse transcription
      polymerase chain reaction and Western blotting. Aortic tissue was stained for
      total collagen, neutrophils, and macrophages using immunohistochemistry on days 4
      and 7. RESULTS: At 7 and 14 days after perfusion, aortic diameter increased in
      elastase-perfused males compared with females (P < .001 for each). At 4 and 7
      days postperfusion, significantly more neutrophils and macrophages were present
      in elastase-perfused males compared with females. By 7 days postperfusion,
      protein levels of transforming growth factor-beta 1 were less in males compared
      with females (P = .04). Type I collagen levels also decreased on days 7 (P <
      .001) and 14 (P = .002), and type III collagen levels decreased on days 7 (P <
      .001) and 14 (P < .001) in males compared with females. With Masson's trichrome
      stain, less adventitial collagen was observed in the elastase-perfused males
      compared with females. MMP-13 expression (P < .001) and protein levels (P = .006)
      in elastase-perfused males were greater than females on day 14. CONCLUSION: This
      study documents a decrease in types I and III collagen with a concurrent increase
      in MMP-13 after elastase perfusion in males compared with females. These data
      suggest that alterations in extracellular matrix collagen turnover may be
      responsible for altered abdominal aortic aneurysm formation between sexes.

PMID- 19767054
TI  - Toxicological and ecotoxic impact of secondary and tertiary treated sewage
      effluents.
AB  - Secondary sewage effluents are discharged in significant quantities in aquatic
      environments delivering pollutants that were not removed during treatment; yet
      advanced treated effluents are not lacking of contaminants. In this study,
      biochemical biomarkers were measured in liver and kidney of rainbow trout
      (Oncorynchus mykiss) exposed to unchlorinated, chlorinated and tertiary treated
      secondary sewage effluents. In addition, organic matter, nitrogen and suspended
      solids were assayed, while a common bioassay, Daphnia magna 21d reproduction test
      was also applied in order to examine potential relation between the performed
      bioassay and the biomarkers. Processes using oxidative conditions, such as
      ozonation and chlorination, resulted in significantly increased breeding rate (up
      to 74%) of the organism. Biomarkers measurements incorporated the determination
      of total glutathione (GSH), glutathione S-transferases (GST), glutathione
      peroxidase (GPX), lipid peroxidation (LPO) and an innovative biomarker in such
      applications, haem peroxidase. In general, the response of biomarkers was
      dependent upon the treatment method and it was tissue specific. Secondary
      effluents inhibited liver GST and haem peroxidase, while GSH levels and LPO were
      significantly provoked in liver. Ozonation provoked hepatic peroxidation, in
      terms of haem peroxidase and LPO, and GST; while the protective (to Reactive
      Oxidant Species - ROS) GSH was depleted, suggesting extended ROS attack to the
      organism. Similar response of biomarkers (but to a lesser extend) was observed
      after exposure of trout to effluents submitted to both coagulation and ozonation,
      emphasizing the significance of removing the residual organic matter by other
      methods than oxidative ones. Ozonation also enhanced renal LPO and GPX; however
      the former employment of coagulation limited the peroxidation phenomena.
      Chlorination mainly affected the levels of total GSH in both tissues.

PMID- 19767055
TI  - Seasonal variation in membrane fouling in membrane bioreactors (MBRs) treating
      municipal wastewater.
AB  - We investigated seasonal variation in membrane fouling in membrane bioreactors
      (MBRs) treating municipal wastewater regarding the difference between physically
      reversible and irreversible fouling. Two separate MBRs with different solid
      retention times (SRTs) operated in parallel for about 200 days including high-
      and low-temperature periods to evaluate the effect of operating conditions on
      seasonal variation of membrane fouling. Seasonal variations of both types of
      membrane fouling (i.e., physically reversible and irreversible fouling) were
      observed for the MBR with short SRT (13 days). However, in the MBR with long SRT
      (50 days), there were no significant seasonal variations in both types of
      membrane fouling. In the MBR with short SRT, the trends in the seasonal variation
      in the development rates of physically reversible and irreversible fouling were
      different. Physically reversible fouling was more significant in the low
      temperature period, while physically irreversible fouling developed more rapidly
      in the high-temperature period. The development rates of physically reversible
      fouling can be related to the concentration of dissolved organic matter in the
      mixed liquor suspension of MBRs; whereas those of physically irreversible fouling
      could not be explained by the concentration of dissolved organic matter. The
      characteristics of dissolved organic matter differed depending on the temperature
      period, and the trends of dissolved organic matter variation in mixed liquor were
      similar with those of foulants that caused physically irreversible fouling. The
      results obtained in this study indicated that seasonal variation in physically
      reversible and irreversible fouling is related to changes in quantity and quality
      of organic matter, respectively.

PMID- 19767056
TI  - Effect-directed analysis of contaminated sediment from the wastewater canal in
      Pancevo industrial area, Serbia.
AB  - Wastewater canal (WWC) in Pancevo industrial area in Serbia, whose main
      environmental receptor is the River Danube, is a well known hot-spot of
      contamination. WWC sediments have been assessed by UNEP based on chemical target
      analysis. However, integrative biological data on exposure to hazardous compounds
      are only provided by the present study which aims at evaluating whether the
      monitored compounds sufficiently reflect potential hazards and to suggest
      additional compounds to include in monitoring and hazard assessment by applying
      effect-directed analysis (EDA) based on arylhydrocarbon receptor-mediated
      activity and cytotoxicity. Multistep NP-HPLC fractionation provided 18 fractions
      co-eluting with polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p
      dioxins (PCDDs), polycyclic aromatic hydrocarbons (PAHs) and more polar
      compounds. PAHs fractions exhibited great potencies to induce ethoxyresorufin-o
      deethylase (EROD) in H4IIE rat hepatoma cell line expressed as 2,3,7,8
      tetrachlorodibenzo-p-dioxin equivalents (TCDD-EQ) (0.1-34.6 x 10(3) pg g(-1)dry
      weight). Chemical analysis of the most active fractions revealed great
      concentrations of PAHs (up to 292 x 10(2)ngg(-1) sediment equivalents (SEQ)),
      methylated PAHs (up to 900 x 10(2) ng g(-1) SEQ), and other alkyl-substituted
      PAHs. Only minor portions of biologically derived TCDD-EQs could be attributed to
      monitored PAHs with known relative potencies (REPs). We hypothesize that a major
      part of the activity is due to non-monitored alkylated and heterocyclic PAHs.
      Results of the cell cytotoxicity/proliferation assay on H4IIE cell line suggest
      the presence of sediment pollutants with pronounced potency to disturb cell
      growth.

PMID- 19767057
TI  - Occurrence of diclofenac and its metabolites in surface water and effluent
      samples from Karachi, Pakistan.
AB  - Diclofenac and five of its transformation products were identified in Malir River
      and Lyari River water as well as in effluent samples from Karachi, Pakistan. To
      the best of our knowledge, this is the first report on the identification of 3'
      hydroxydiclofenac and 8-chlorocarbazole-1-yl-ethanoic acid in environmental
      samples. Their estimated concentrations ranged between 0.08-0.3 microg L(-1) and
      0.03-0.4 microg L(-1), respectively. In addition, 4'- and 5-hydroxydiclofenac as
      well as 1-(2,6-dichlorophenyl)-1,3-dihydro-2H-indole-2-one were detected in the
      samples at concentrations between 0.4-1.8, 0.01-0.3, and 0.02-0.2 microg L(-1),
      respectively. The hydroxy derivatives seem to reflect human excretions via
      household wastewater, while the chlorocarbazole derivative is related to abiotic
      photolytic transformation of diclofenac.

PMID- 19767058
TI  - A GIS-based human health risk assessment for urban green space planning--an
      example from Grugliasco (Italy).
AB  - The need to develop approaches for risk-based management of soil contamination,
      as well as the integration of the assessment of the human health risk (HHR) due
      to the soil contamination in the urban planning procedures has been the subject
      of recent attention of scientific literature and policy makers. The spatial
      analysis of environmental data offers multiple advantages for studying soil
      contamination and HHR assessment, facilitating the decision making process. The
      aim of this study was to explore the possibilities and benefits of spatial
      implementation of a quantitative HHR assessment methodology for a planning case
      in a typical urban environment where the soil is contaminated. The study area is
      located in the city of Grugliasco a part of the Turin (Italy) metropolitan area.
      The soils data were derived from a site specific soil survey and the land-use
      data from secondary sources. In the first step the soil contamination data were
      geo-statistically analysed and a spatial soil contamination data risk modelling
      procedure designed. In order to spatially assess the HHR computer routines were
      developed using GIS raster tools. The risk was evaluated for several different
      land uses for the planned naturalistic park area. The HHR assessment indicated
      that the contamination of soils with heavy metals in the area is not sufficient
      to induce considerable health problems due to typical human behaviour within the
      variety of urban land uses. An exception is the possibility of direct ingestion
      of contaminated soil which commonly occurs in playgrounds. The HHR evaluation in
      a planning case in the Grugliasco Municipality confirms the suitability of the
      selected planning option. The construction of the naturalistic park presents one
      solution for reducing the impacts of soil contamination on the health of
      citizens. The spatial HHR evaluation using GIS techniques is a diagnostic
      procedure for assessing the impacts of urban soil contamination, with which one
      can verify planning options, and provides an important step in the integration of
      human health protection within urban planning procedures.

PMID- 19767059
TI  - Trophodynamics of mercury and other trace elements in a pelagic food chain from
      the Baltic Sea.
AB  - Mercury (Hg) and 13 other trace elements (Al, Ti, V, Cr, Fe, Mn, Co, Ni, Cu, Zn,
      As, Cd, and Pb) were measured in phytoplankton, zooplankton, mysis and herring in
      order to examine the trophodynamics in a well-studied pelagic food chain in the
      Baltic Sea. The fractionation of nitrogen isotopes (delta(15)N) was used to
      evaluate food web structure and to estimate the extent of trophic
      biomagnification of the various trace elements. Trophic magnification factors
      (TMFs) for each trace element were determined from the slope of the regression
      between trace element concentrations and delta(15)N. Calculated TMFs showed
      fundamental differences in the trophodynamics of the trace elements in the
      pelagic food chain studied. Concentrations of Al, Fe, Ni, Zn, Pb and Cd showed
      statistically significant decreases (TMF<1) with increasing trophic levels and
      thus these trace elements tropically dilute or biodilute in this Baltic food
      chain. Cu, As, Cr, Mn, V, Ti and Co showed no significant relationships with
      trophic levels. Hg was unique among the trace elements studied in demonstrating a
      statistically significant increase (TMF>1) in concentration with trophic level
      i.e. Hg biomagnifies in this Baltic food chain. The estimated TMF for Hg in this
      food chain was comparable to TMFs observed elsewhere for diverse food chains and
      locations.

PMID- 19767060
TI  - Acidic polysaccharide of Panax ginseng as a defense against small intestinal
      damage by whole-body gamma irradiation of mice.
AB  - An acidic polysaccharide of Panax ginseng (APG), ginsan, has been reported to
      protect the hematopoietic system by increasing the number of bone marrow cells
      and spleen cells. Therefore, we evaluated the ability of APG to protect mice from
      radiation-induced damage of the small intestine. APG treatment caused the
      lengthening of villi and a numerical increase of crypt cells in the small
      intestine at 3.5 days after 7Gy irradiation compared to irradiated, non-treated
      controls. In addition, APG significantly inhibited irradiation-induced apoptosis
      by decreasing the amount of pro-apoptotic p53 and Bax as well as augmenting that
      of anti-apoptotic Bcl-2 at 24h after irradiation. These results indicate that APG
      might be a useful adjunct to therapeutic irradiation as a protective agent for
      the gastrointestinal tract of cancer patients.

PMID- 19767061
TI  - Heterogeneous levels of oxidative phosphorylation enzymes in rat adrenal glands.
AB  - Mitochondria are organelles that produce ATP and reactive oxygen species, which
      are thought to be responsible for a decline in physiological function with aging.
      In this study, we morphologically and biochemically examined mitochondria in the
      rat adrenal gland. Immunohistochemistry showed that the rank order for intensity
      of immunolabelling for complex IV was zona reticularis > zona fasciculata >>
      adrenal medulla, whereas for complex V alpha and beta subunits, it was zona
      fasciculata > zona reticularis and adrenal medulla. The immunolabelling for
      complex I was homogeneous in the adrenal gland. The difference in immunolabelling
      between complexes I and IV indicates that the ratio of levels of complex I to
      that of complex IV in the zona reticularis was smaller than that in the zona
      fasciculata and the adrenal medulla. Electron microscopy revealed that aging rats
      had zona reticularis cells with many lysosomes and irregular nuclei. The result
      suggests that the level of proteins involved in oxidative phosphorylation is
      coordinated within the complex, but differs between the complexes. This might be
      responsible for degeneration of zona reticularis cells with aging.

PMID- 19767062
TI  - Newly formed skeletal muscle fibers are prone to false positive immunostaining by
      rabbit antibodies.
AB  - Reports on muscle biology and regeneration often implicate
      immuno(cyto/histo)chemical protein characterization using rabbit polyclonal
      antibodies. In this study we demonstrate that newly formed myofibers are
      especially prone to false positive staining by rabbit antibodies and this
      unwanted staining is only recognized (1) by a negative muscle tissue control that
      does not harbor the protein to be examined (fx. from knockout mouse) or (2) by
      use of a nonsense rabbit antibody that has been prepared in the same way as the
      antibody of interest. However, many muscle immuno(cyto/histo)chemical studies
      only rely on controls that reveal non-specific binding by the secondary antibody
      and neglect that the primary rabbit antibody itself may cause false positive
      staining of the muscle. We suggest that reliable immuno-based protein detection
      in newly formed muscle fibers at least requires a nonsense rabbit antibody and
      optimally a negative muscle/cell control.

PMID- 19767063
TI  - Association between the N-terminally truncated (DeltaN) p63alpha (DeltaNp63alpha)
      isoform and debulking status, VEGF expression and progression-free survival in
      previously untreated, advanced stage epithelial ovarian cancer: A Gynecologic
      Oncology Group study.
AB  - OBJECTIVES: The Gynecologic Oncology Group (GOG) examined the association between
      the relative expression of the DeltaNp63alpha isoform and clinicopathologic
      variables, p53 status, angiogenic markers, progression-free survival (PFS) and
      overall survival (OS) in epithelial ovarian cancer (EOC). METHODS: Immunoblot
      analysis was used to determine the relative expression of DeltaNp63alpha to beta
      actin in lysates of frozen primary tumor from women with previously untreated,
      advanced stage EOC who participated in a GOG specimen banking protocol and a
      randomized phase III treatment protocol. RESULTS: DeltaNp63alpha was detected in
      49/56 (87.5%) cases with relative expression ranging from 0 to 4.55
      (median=0.325). A correlation was observed between the relative expression of
      DeltaNp63alpha and debulking status (Spearman's correlation coefficient=0.303;
      p=0.025) and the relative expression of vascular endothelial growth factor (VEGF)
      (Spearman's correlation coefficient=0.303; p=0.045), but not with p53 status
      (overexpression or mutation), immunoblot expression of MASPIN, or the relative
      expression of thrombospondin-1, basic fibroblast growth factor or VEGF receptor
      1. A 1.4-fold increase was observed in the risk of disease progression for each
      unit increase in the relative expression of DeltaNp63alpha using an unadjusted
      (hazard ratio [HR]=1.459; 95% confidence interval [CI]=1.096-1.942; p=0.010), a
      full (HR=1.483; 95% CI=1.060-2.076; p=0.021) and a reduced (HR=1.387; 95%
      CI=1.025-1.877; p=0.034) Cox regression model. The relative expression of
      DeltaNp63alpha was not associated with OS using an unadjusted, a full or a
      reduced Cox model. CONCLUSIONS: The relative expression DeltaNp63alpha appears to
      be associated with debulking status and the relative expression of VEGF and PFS,
      and to be an independent prognostic factor for disease progression in EOC.

PMID- 19767064
TI  - Improving sentinel lymph node detection rates in endometrial cancer: how many
      cases are needed?
AB  - OBJECTIVE: To describe sentinel lymph node (SLN) detection rates in endometrial
      cancer and estimate how many cases are needed to achieve >90% SLN detection.
      METHODS: We conducted a prospective study of patients undergoing primary surgery
      for endometrial cancer between September 2005 and March 2009. Lymph node mapping
      was performed using blue dye injection into the cervix in all cases. Additional
      injection methods included blue dye injection in the uterine fundus, and cervical
      injection of Tc99m. SLNs were identified and removed, followed by regional lymph
      node dissection. The results were analyzed according to two study periods: an
      "early" phase (September 2005-December 2007) and a "late" phase (January 2008
      March 2009). RESULTS: One hundred and fifteen patients with endometrial cancer
      were included. The cervix was the only site of injection in 82 cases (71%), while
      a combined cervical and fundal injection was performed in 33 cases (29%).
      Overall, SLN detection was achieved in 98 (85%) cases. In the initial 27 months
      of the study, a SLN was identified in 50 of 64 cases (78%), with 2 false negative
      cases. In the subsequent 15 months, successful mapping was achieved in 48 of 51
      cases (94%) with no false negative cases. When examining an individual provider's
      performance, after the first 30 cases, the rate of successful mapping
      significantly increased from 77% to 94% (P=0.033). CONCLUSION: Sentinel node
      mapping in uterine cancer requires a dedicated effort to achieve high detection
      rates. Surgeons should determine their individual detection rates and false
      negative rates. Our data demonstrate that high SLN detection rates can be
      achieved in women with uterine cancer and increasing surgical volume (30 cases)
      is associated with significantly increased detection rates.

PMID- 19767065
TI  - Hormone receptor expression in uterine sarcomas: prognostic and therapeutic
      roles.
AB  - OBJECTIVES.: The utility of hormone therapy in the management of uterine sarcomas
      is poorly defined. We hypothesize that estrogen receptor (ER) expression is
      common in uterine sarcomas, and carries prognostic significance. Further, we
      hypothesize that ER-positive uterine sarcomas respond to hormone therapy.
      METHODS.: We retrospectively reviewed charts of patients with uterine sarcomas.
      Stepwise Cox proportional hazards regression model was used to evaluate variables
      related to the risk of death: age, histology, stage, use of pelvic radiotherapy,
      and ER expression. In addition, we examined clinical outcomes in patients treated
      with aromatase inhibitors, megestrol acetate, depot medroxyprogesterone acetate,
      and tamoxifen. RESULTS.: Fifty-four patients underwent immunohistochemical
      staining, and 34 (63%) were ER-positive. Kaplan-Meier survival analysis and log
      rank test indicated that patients with ER-positive sarcomas demonstrated improved
      overall survival when compared with ER-negative patients (median OS 36 vs. 16
      months, p=0.004). Upon multivariate analysis, ER positivity retained significance
      as an independent predictor of survival (HR=0.32, CI 0.12-0.89, p=0.03). Four
      patients received hormonal treatment in the adjuvant setting and remained in
      remission (range of follow up: 18-68 months). Eighteen patients received hormone
      therapy in the setting of recurrent or progressive disease: fourteen (78%)
      demonstrated stable disease or complete or partial response (range of follow up:
      6-124 months). CONCLUSIONS.: ER expression is common and is associated with
      improved overall survival in uterine sarcomas. Conducting immunohistochemical
      staining to ascertain ER status may aid with prognostication in this disease.
      Hormone therapy should be considered in patients with primary and recurrent ER
      positive uterine sarcomas.

PMID- 19767066
TI  - Extreme drug resistance assay does not influence survival in women with
      epithelial ovarian cancer.

PMID- 19767067
TI  - Prognostic significance of positive peritoneal cytology in adenocarcinoma of the
      uterine cervix.
AB  - OBJECTIVE: A retrospective analysis was carried out to evaluate the prognostic
      significance of peritoneal cytology in cervical adenocarcinoma. METHODS: The
      records of 107 patients with FIGO stage IB to IIB cervical adenocarcinoma who
      underwent hysterectomy were reviewed. RESULTS: Sixteen patients (15%) had
      positive peritoneal cytology. The 5-year survival rate among patients with
      positive or negative cytology was 50% or 87%, respectively, showing a significant
      difference (log-rank, P<0.001). The recurrence-free survival (RFS) rate at 36
      months in the cytology-positive or -negative group was 53% or 87%, respectively,
      the difference being significant (log-rank, P=<0.001). Cox model analysis
      revealed positive cytology [hazards ratio (HR) 6.27, 95% confidence interval (CI)
      2.13-18.41], positive lymph node (HR 6.20, 95% CI 1.87-20.57), ovarian metastasis
      (HR 5.20, 95% CI 1.18-22.82), and histological grade (HR 5.97, 95% CI 2.00-17.78)
      to be independent adverse risk factors for survival among the factors analyzed
      (lymph node status, lymph-vascular space invasion, tumor size, depth in cervical
      wall, pathological parametrial involvement, infiltration to vagina, ovarian
      metastasis, and histological grade). Cox model analysis showed that positive
      cytology (HR 4.58, 95% CI 1.48-14.16), positive lymph node (HR 7.61, 95% CI 2.69
      21.54), and histological grade (HR6.13, 95% CI 2.14-17.77) were independent
      adverse risk factors for RFS. The incidence of peritoneal spread at the first
      recurrence among the cytology-positive group (62.5%) was significantly higher
      than that among the cytology-negative group (12.5%) (Fisher's exact test,
      P=0.021). CONCLUSION: The presence of positive peritoneal cytology appears to be
      an independent prognostic risk factor in patients with cervical adenocarcinoma.

PMID- 19767068
TI  - Cyclosporin A reduces CD4(+)CD25(+) regulatory T-cell numbers in patients with
      atopic dermatitis.

PMID- 19767069
TI  - Reduced central tolerance in Omenn syndrome leads to immature self-reactive
      oligoclonal T cells.
AB  - BACKGROUND: Omenn syndrome (OS) is characterized by a peculiar severe T-cell
      immune deficiency associated with autoimmunelike manifestations. Dysregulations
      of the central and peripheral immune tolerance, mediated by the protein
      autoimmune regulator (AIRE) and regulatory T cells, respectively, were proposed
      as possible mechanisms of this aberrant inflammatory process. OBJECTIVE: We
      studied mechanisms of central and peripheral tolerance in patients with OS and
      also examined the gene expression profile associated with OS features. METHODS: T
      cell receptor diversity, DNA rearrangement, and the expression of AIRE and
      forkhead box P3 mRNA as well as the expression of regulatory T cells in cells
      obtained from patients with OS were studied. Characterization of gene expression
      in these cells was carried out by using the TaqMan Low-Density Array. RESULTS:
      Transcript expression of peripheral blood AIRE but not forkhead box P3 was
      reduced in patients with OS. The expression of natural killer T and regulatory T
      cells was normal, although the latter showed an abnormal CD4-negative population.
      Patients with OS have oligoclonal T cells with limited DNA recombination
      activity, including the presence of early but not late T-cell maturation events,
      regardless of the genetic defect underlying the syndrome. The transcriptional
      profile associated with OS features reveals significant changes in 25.5% of the
      tested genes compared with normal control. CONCLUSION: Our findings suggest that
      T-cell oligoclonal expansion in OS emanates from an incomplete block before the
      maturation stage of negative selection, which may explain escape of autoreactive
      T cells from the thymus. Dysregulated genes in patients with OS are closely
      involved with self-tolerance and autoimmunity.

PMID- 19767070
TI  - The minimally important difference of the Asthma Control Test.
AB  - BACKGROUND: The Asthma Control Test (ACT) has been well validated, but a
      minimally important difference (MID) has not been established. OBJECTIVE: We
      sought to identify an MID for the ACT. METHODS: Data come from 4 independent
      samples of adult asthmatic patients. Distributional methods for determining the
      MID included 0.5 SD, 1 SEM, and 2 SEM. Anchor-based methods assessed the
      relationship of differences in ACT scores to (1) self-reported asthma severity,
      (2) asthma episode frequency in the past 4 weeks, (3) physician ratings of asthma
      control, (4) physician recommendation of a change in therapy, (5) FEV(1), (6) the
      risk over the next 12 months of excess short-acting beta-agonist use and
      exacerbations, and (7) patient-defined changes in asthma course over 3 months.
      RESULTS: Four thousand one hundred eighteen patients completed the ACT. The 0.5
      SD criterion for MID ranged from 2.03 to 2.45 points (mean, 2.2 points). The 1
      SEM criterion ranged from 1.77 to 2.05 points (mean, 1.88 points), and the 2 SEM
      criterion ranged from 3.55 to 4.10 points (mean, 3.75 points). Differences in
      mean ACT scores across patient groups differing on criterion measures ranged from
      1.06 to 5.28 points (mean, 3.1 points). Predictive analyses showed that a
      difference of 3 points on the ACT was associated with a subsequent 76% increased
      risk (95% CI, 73% to 79%) of excess short-acting beta-agonist use and a 33%
      increased risk (95% CI, 31% to 35%) of exacerbations. CONCLUSION: The data
      support an MID for the ACT of 3 points.

PMID- 19767071
TI  - A pilot study of equal doses of 10% IGIV given intravenously or subcutaneously.

PMID- 19767072
TI  - Expression of chemokines and chemokine receptors in lesional and nonlesional
      upper skin of patients with atopic dermatitis.
AB  - BACKGROUND: Trafficking of dendritic cell (DC) subtypes to and from the skin
      plays a pivotal role in atopic dermatitis (AD). OBJECTIVES: We sought to
      determine the CCR pattern of epidermal DC subtypes and CCL expression in relation
      to the state of AD. METHODS: Shave biopsy specimens were taken from patients with
      AD before and after 24 and 72 hours of atopy patch testing and from the skin of
      patients with chronic AD, skin of patients with psoriasis, and healthy skin. CCR
      expression of epidermal DCs was studied by using flow cytometry, and chemokine
      mRNA levels in the skin were quantified by means of real-time PCR. RESULTS: The
      total number of CD1a(+) epidermal DCs increased and the proportion of Langerin
      positive CD1a(+) DCs decreased whereas the percentage of Langerin-negative
      CD1a(+) DCs increased after allergen application. Expression of CCR5 and CCR6 of
      Langerin-negative CD1a(+) DCs was characteristic for acute AD. Expression of
      CCL1, CCL3, CCL4, and CCL11 mRNA was greater in patients with acute AD versus
      that seen in patients with chronic AD. Only a strong increase of CCLs, in
      particular CCL1, CCL17, and CCL18, went along with eczema development, and
      increased CCL1, CCL13, CCL17 and CCL18 expression was specific for patients with
      chronic AD compared with those with psoriasis. CONCLUSION: Modified recruitment
      and differentiation of DCs from their dermal and blood precursors occurs in the
      acute phase of AD. A boost in the amplitude of CCLs after allergen application
      goes along with eczema development.

PMID- 19767073
TI  - Elevated serum cytokines during human anaphylaxis: Identification of potential
      mediators of acute allergic reactions.
AB  - BACKGROUND: Anaphylaxis is generally unanticipated and requires emergency
      management. Therefore, the biological mediators in human beings have been
      difficult to define. OBJECTIVE: Our aim was to identify cytokines and chemokines
      whose concentrations increase during anaphylaxis in human beings and to determine
      how each correlates with severity. METHODS: We measured the concentrations of
      potential mediators, including cytokines, chemokines, mast cell tryptase (MCT),
      and histamine, over 3 time points in 76 patients presenting to emergency
      departments with anaphylaxis and correlated these with a global severity scale,
      hypotension, and hypoxia. RESULTS: IL-2, IL-6, IL-10, TNF receptor I, MCT, and
      histamine were significantly elevated in patients with severe reactions (n = 36)
      compared with moderate reactions (n = 40) and healthy controls. Histamine levels
      peaked at emergency department arrival, whereas other mediators peaked later. IL
      4, IL-5, IL-13, IFN-gamma, and TNF-alpha were marginally elevated in severe
      reactions compared with healthy controls but did not correlate with reaction
      severity. Severe reactions tended to be either hypotensive (n = 19) or hypoxemic
      (n = 12). Levels of IL-6, IL-10, TNF receptor I, MCT, and histamine correlated
      with hypotension. No mediator correlated with hypoxemia or other respiratory
      features. CONCLUSION: This study confirms that the concentrations of a number of
      cytokines are elevated in blood during anaphylaxis in human beings and that some
      correlate with the presence of hypotension. Others were only marginally elevated
      within a concentration range that available assays do not reliably detect. During
      respiratory reactions, mediators may be largely confined to the airways so that
      blood concentrations do not reflect activity.

PMID- 19767074
TI  - Exhaled nitric oxide levels in asthma: Personal best versus reference values.
AB  - BACKGROUND: Factors affecting the fraction of nitric oxide in exhaled air
      (FE(NO)) are multiple. Interpreting values when assessing airways disease may be
      problematic. Clinically optimum levels have not been defined. OBJECTIVES: We
      aimed to establish the relationship between predicted values for FE(NO) obtained
      from equations by Olin et al, Travers et al, and Dressel et al, and normalized
      levels after oral prednisone. We also compared postprednisone FE(NO) levels with
      those obtained during optimized treatment with inhaled fluticasone. METHODS: Data
      were obtained before and after a trial of oral prednisone (30mg/d for 14 days),
      and also from a previously published study in which patients had their dose of
      inhaled corticosteroid adjusted using either FE(NO) or symptoms/lung function to
      optimize treatment. RESULTS: Seventy-three patients completed the study. The
      geometric mean FE(NO) after prednisone (17.7 parts per billion [ppb]; 95% CI,
      15.5-20.2) was significantly lower than mean FE(NO) at the optimized fluticasone
      dose (20.2 ppb; 95% CI, 17.1-23.8; P=.04) and at loss of control (27.6 ppb; 95%
      CI, 22.8-33.4; P < .001). FE(NO) levels after prednisone did not differ
      significantly from the predicted values of Olin et al (16.8 ppb, 95% CI, 16.0
      17.5; P=.44), but were significantly lower than values of Travers et al
      (predicted, 21.5 ppb; 95% CI, 20.9-22.2; P=.005) and Dressel et al (predicted,
      27.8 ppb; 95% CI, 26.7-28.9; P < .001). CONCLUSIONS: Optimum FE(NO) levels are
      best established by using oral rather than inhaled steroid treatment, and these
      approximate to predicted values from the reference equation by Olin et al.
      However, at optimized doses of inhaled corticosteroid, although FE(NO) levels
      were higher than predicted, asthma was well controlled. Targeting FE(NO) on
      reference values is not justified.

PMID- 19767075
TI  - The LOCAL Study: Local reactions do not predict local reactions in allergen
      immunotherapy.
AB  - BACKGROUND: Although previous immunotherapy studies have demonstrated that a
      local reaction does not predict a systemic reaction, no study has investigated
      whether a local reaction predicts a local reaction. OBJECTIVE: To determine
      whether a local reaction predicts a local reaction at the next immunotherapy
      injection. METHODS: A retrospective analysis of an electronic immunotherapy
      database over a 12-month period was performed at a single site that did not dose
      adjust for local reactions. Total injections, small local reactions (less than or
      equal to the size of patient's palm), large local reactions (LLRs; larger than
      the patient's palm), systemic reactions, and whether a local reaction was
      followed by a local reaction were recorded. RESULTS: Between August 2005 and July
      2006, 360 patients received a total of 9678 injections. Of all patients, 78.3%
      had at least 1 local reaction, and 7.5% had an LLR. The total local reaction rate
      was 16.3% (1574/9678), the small local reaction rate was 15.9% (1536/9678), and
      the LLR rate was 0.4% (38/9678). Of all local reactions followed by another
      injection, 27.2% were followed by a local reaction. The sensitivity and positive
      predictive value for a local reaction predicting a local reaction at the next
      injection were 26.2% and 27.2%, respectively. In contrast, the specificity for
      the absence of a local reaction predicting the absence of a subsequent local
      reaction was 85.5%. For LLRs, only 6.0% were followed by another LLR; the
      sensitivity, positive predictive value, and specificity were 5.2%, 6.0%, and
      99.6%, respectively. CONCLUSION: In a clinic that does not dose-adjust for local
      reactions, local reactions do not predict local reactions at the next
      immunotherapy injection.

PMID- 19767076
TI  - Natural killer T cells in bronchial biopsies from human allergen challenge model
      of allergic asthma.

PMID- 19767077
TI  - The occupant as a source of house dust bacteria.
AB  - BACKGROUND: Markers for microbial groups are commonly measured in house dust
      samples to assess indoor exposure to microbes in studies on asthma and allergy.
      However, little is known about the sources of different microbes. A better
      understanding of the nature and origin of microbes present in the immediate
      environment of human beings is crucial if one wants to elucidate protective as
      well as adverse effects on human health. OBJECTIVE: To determine the extent to
      which the bacterial composition of mattress and floor dust reflects the presence
      of the human body in relation to other environmental sources. METHODS: House dust
      and skin surface swab samples of occupants in 4 homes were collected and analyzed
      for their bacterial content, using a culture-independent methodology. Bacterial
      sequences analyzed from the different house dusts and skin surface swabs
      represented random samples of bacteria present in a given sample. Highly similar
      sequences were grouped to assess biodiversity and to draw conclusions about the
      sources of bacteria. RESULTS: The bacterial flora in the house dust samples was
      found to be highly diverse and dominated by gram-positive bacteria. To a
      considerable extent, the presence of different bacterial groups was attributed to
      human sources. In the individuals' mattress dust samples, 69% to 88% of the
      bacterial sequences analyzed were associated with human origins. The respective
      percentages for the individual floor dusts ranged from 45% to 55%. CONCLUSION:
      Our study indicates that human-derived bacteria account for a large part of the
      mainly gram-positive bacterial content in house dust.

PMID- 19767078
TI  - Efficacy of human C1 esterase inhibitor concentrate compared with placebo in
      acute hereditary angioedema attacks.
AB  - BACKGROUND: Hereditary angioedema caused by C1 esterase inhibitor deficiency is a
      rare disorder. OBJECTIVE: To compare the efficacy of pasteurized C1 esterase
      inhibitor concentrate (Berinert, CSL Behring) at intravenous doses of 10 or 20
      U/kg body weight with placebo in the treatment of single, acute abdominal or
      facial attacks in patients with hereditary angioedema. METHODS: This was a
      randomized, double-blind, placebo-controlled study in 125 patients with type I or
      II hereditary angioedema. The primary outcome was time from start of treatment to
      onset of symptom relief. Secondary outcomes were time to complete resolution,
      proportion of patients with worsened intensity of angioedema symptoms between 2
      and 4hours after treatment, and number of vomiting episodes within 4 hours.
      RESULTS: Median time to onset of relief was significantly shorter with C1
      esterase inhibitor concentrate at a dose of 20 U/kg than with placebo (0.5 vs 1.5
      hours; P = .0025), whereas with 10 U/kg, the time to onset of relief was only
      slightly shorter than with placebo (1.2 vs 1.5 hours; P = .2731). Compared with
      placebo, the reduction in time to onset of relief was greatest for severe attacks
      (0.5 vs 13.5 hours). The secondary outcomes consistently supported the efficacy
      of the 20 U/kg dose. C1 esterase inhibitor concentrate was safe and well
      tolerated. No seroconversions were observed for HIV, hepatitis virus, or human
      B19 virus. CONCLUSION: C1 esterase inhibitor concentrate given intravenously at a
      dose of 20 U/kg is an effective and safe treatment for acute abdominal and facial
      attacks in patients with hereditary angioedema, with a rapid onset of relief.

PMID- 19767079
TI  - Associations of functional NLRP3 polymorphisms with susceptibility to food
      induced anaphylaxis and aspirin-induced asthma.
AB  - BACKGROUND: NLR family, pyrin domain containing 3 (NLRP3), controls the activity
      of inflammatory caspase-1 by forming inflammasomes, which leads to cleavage of
      the procytokines IL-1beta and IL-18. Recent studies have shown associations of
      human NLRP3 polymorphisms with susceptibility to various inflammatory diseases;
      however, the association with allergic diseases remains unclear. OBJECTIVE: We
      sought to examine whether NLRP3 polymorphisms are associated with susceptibility
      to food allergy, food-induced anaphylaxis, and aspirin-induced asthma (AIA).
      METHODS: We selected 15 tag single nucleotide polymorphisms (SNPs) of NLRP3 and
      conducted association analyses of NLRP3 using 574 and 1279 samples for food
      allergy and AIA, respectively. We further performed functional analyses of the
      susceptible SNPs. RESULTS: Two NLRP3 SNPs (rs4612666 and rs10754558) were
      significantly associated with susceptibility to food-induced anaphylaxis (P =
      .00086 and P = .00068, respectively). The NLRP3 haplotype of the 2 SNPs also
      showed a significant association (P = .000098). We could confirm the association
      with susceptibility to another hypersensitivity phenotype, AIA (rs4612666, P =
      .0096). Functional analysis revealed that the risk alleles of rs4612666 and
      rs10754558 increased the enhancer activity of NLRP3 expression and NLRP3 mRNA
      stability, respectively. CONCLUSION: Our results indicate that the NLRP3 SNPs
      might play an important role in the development of food-induced anaphylaxis and
      AIA in a gain-of-function manner. Further research on the NLRP3 inflammasome will
      contribute to the development of novel diagnostic and therapeutic methods for
      food-induced anaphylaxis and AIA.

PMID- 19767081
TI  - The acetaminophen and asthma hypothesis 10 years on: A case to answer.

PMID- 19767083
TI  - Thymic stromal lymphopoietin induction by polyinosinic:polycytidylic acid in
      human keratinocytes is preferentially mediated through protein kinase R and
      retinoid-inducible gene I and not Toll-like receptor 3.

PMID- 19767084
TI  - Modulation by aspirin of nuclear phospho-signal transducer and activator of
      transcription 6 expression: Possible role in therapeutic benefit associated with
      aspirin desensitization.
AB  - BACKGROUND: Aspirin-exacerbated respiratory disease is characterized by asthma,
      nasal polyps, and intolerance to aspirin with overexpression of leukotriene (LT)
      C(4) synthase and cysteinyl leukotriene receptors. Through an unknown mechanism,
      aspirin desensitization is an effective treatment. OBJECTIVE: We hypothesized
      that aspirin desensitization blocks IL-4-induced expression of these LT
      activities through inhibition of signal transducer and activator of transcription
      6 (STAT6)-mediated transcription. METHODS: Nuclear extracts were derived from THP
      1 and normal human monocytes resting and cocultured with aspirin before IL-4
      stimulation. Quantitative PCRs were conducted. Electrophoretic mobility shift
      assays were performed by using oligomers for STAT6 sites within the LT receptor
      and synthase promoters. Western blots of nuclear extracts were probed by using
      anti-phospho-STAT6 antibodies. RESULTS: Upregulation of LT receptor mRNA by IL-4
      was negated by aspirin and ketorolac but not by sodium salicylate. The STAT6 site
      in the LT receptor and synthase promoters was confirmed by using mobility shift
      assays by competing with unlabeled STAT6 consensus probes and supershifts with
      anti-STAT6 antibodies. Aspirin and ketorolac decreased the IL-4-inducible
      expression of nuclear STAT6 observed in mobility shift assays and Western
      hybridization. CONCLUSION: The LT receptor and synthase promoters have STAT6
      binding sites that are engaged by IL-4-induced nuclear extracts and inhibited by
      aspirin. Assuming that normal monocytes behave like monocytes from patients with
      aspirin-exacerbated respiratory disease, inhibition of IL-4-STAT6 might explain a
      mechanism in aspirin desensitization daily treatment, resulting in downregulation
      of production and responsiveness to cysteinyl leukotrienes. This biologic
      activity of aspirin likely reflects COX inhibition because it was shared with
      ketorolac but not sodium salicylate.

PMID- 19767085
TI  - Associations between prenatal pesticide exposure and cough, wheeze, and IgE in
      early childhood.

PMID- 19767086
TI  - Sperm-mediated gene transfer-treated spermatozoa maintain good quality parameters
      and in vitro fertilization ability in swine.
AB  - A simple and efficient method for producing multitransgenic animals is required
      for medical and veterinary applications. Sperm-mediated gene transfer (SMGT) is
      an effective method for introducing multiple genes into pigs (Sus, Sus scrofa).
      The major benefits of this technique are the high efficiency, low cost, and ease
      of use compared with that of other methods: Sperm-mediated gene transfer does not
      require embryo handling or expensive equipment. The aim of this study was to
      investigate the influence of SMGT treatment and exogenous DNA uptake on sperm
      quality. Even after a coincubation with a 20-fold larger amount (100 microg/mL)
      of DNA than usual (5 microg/mL), sperm quality parameters were not significantly
      affected, confirming the hypothesis that the SMGT protocol itself or the amount
      of bound DNA do not compromise the possibility of an extended employment of SMGT.
      More importantly, we found that semen used for in vitro fertilization 24h after
      DNA uptake gave good cleavage (60% vs. 58%, treated vs. control) and
      developmental rates definitely positive (41% vs. 48%, treated vs. control). These
      good results are connected to a competitive efficiency of transformation (62%)
      due to the numerous improvements in SMGT technique. We demonstrate that SMGT
      treated spermatozoa retain good quality and fertilization potential for at least
      24h, expanding the possibility to apply transgenesis in field conditions in
      swine, where the greatest hurdles are fertilization timing and plain procedure.

PMID- 19767087
TI  - Cholesterol concentration in seminal plasma as a predictive tool for quality
      semen evaluation.
AB  - The aim of this study was to investigate the relationship between lipid
      composition of bovine serum and seminal plasma, seasonality, and semen quality.
      The experiment was carried out in two groups of Simmental breeding bulls: Group I
      (ages 2 to 4 yr) and Group II (ages 5 to 10 yr). Blood samples were collected
      from jugular vein, and bovine semen was sampled with an artificial vagina once
      per season. Serum concentrations of total cholesterol, high-density lipoprotein
      cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C),
      triacylglycerols, nonesterified fatty acids (NEFAs), and lipoprotein
      electrophoretic patterns were determined. Seminal plasma concentrations of total
      cholesterol, HDL-C, and LDL-C were assayed. Serum concentration of
      triacylglycerols in young bulls was significantly higher in winter compared with
      that in autumn, whereas serum NEFA concentration was significantly higher in
      autumn compared with that in other seasons. Serum concentration of total
      cholesterol, LDL-C, and LDL lipoproteins in older bulls was significantly higher
      in winter than in spring. Seminal plasma concentration of total cholesterol in
      young bulls was significantly higher in spring compared with that in summer,
      whereas in older bulls it was significantly higher in winter compared with that
      in autumn samples. Sperm volume of both groups was significantly higher in summer
      compared with that in autumn and winter. Sperm motility in young bulls was lowest
      in summer and differed significantly from the values recorded in other seasons.
      The changes observed in seminal plasma cholesterol concentration were associated
      with extracellular lipid use and appeared to be applicable as a biochemical
      marker of sperm quality.

PMID- 19767088
TI  - Real-time xCELLigence impedance analysis of the cytotoxicity of dental composite
      components on human gingival fibroblasts.
AB  - OBJECTIVES: Aim of this study was by continuous monitoring to assay the
      proliferative capacity of human gingival fibroblasts (HGFs), to investigate
      cytotoxicity of the most common monomers/comonomers in dental resin composites:
      bisphenol-A-glycidylmethacrylate (BisGMA), hydroxyethylenemethacrylate (HEMA),
      triethyleneglycoldimethacrylate (TEGDMA), and urethanedimethacrylate (UDMA) in
      HGFs during 24h exposure using the xCELLigence system. METHODS: xCELLigence cell
      index (CI) impedance measurements were performed according to the instructions of
      the supplier. HGFs were resuspended in medium and subsequently adjusted to
      400,000, 200,000, 100,000, and 50,000 cells/mL. After seeding 100 microL of the
      cell suspensions into the wells of the E-plate 96, HGFs were monitored every 15
      min for a period of up to 18 h by the xCELLigence system. RESULTS: Half maximum
      effect concentrations (EC(50)) were determined based on the dose-response curves
      derived by xCELLigence measurements. Following real-time analysis, significantly
      increased EC(50) values of HGFs exposed for 24h to the following substances were
      obtained: HEMA(a), TEGDMA(b), UDMA(c). The EC(50) values (mean [mmol/L]+/-S.E.M.;
      n=5) were: HEMA 11.20+/-0.3, TEGDMA(a) 3.61+/-0.2, UDMA(a,b) 0.20+/-0.1, and
      BisGMA(a,b,c) 0.08+/-0.1. These results are similar to the EC(50) values
      previously observed with the XTT end-point assay. SIGNIFICANCE: Our data suggests
      that the xCELLigence live cell analysis system offers dynamic live cell
      monitoring and combines high data acquisition rates with ease of handling.
      Therefore, the xCELLigence system can be used as a rapid monitoring tool for
      cellular viability and be applied in toxicity testing of xenobiotics using in
      vitro cell cultures.

PMID- 19767089
TI  - High-dose cytarabine plus high-dose methotrexate versus high-dose methotrexate
      alone in patients with primary CNS lymphoma: a randomised phase 2 trial.
AB  - BACKGROUND: Chemotherapy with high-dose methotrexate is the conventional approach
      to treat primary CNS lymphomas, but superiority of polychemotherapy compared with
      high-dose methotrexate alone is unproven. We assessed the effect of adding high
      dose cytarabine to methotrexate in patients with newly diagnosed primary CNS
      lymphoma. METHODS: This open, randomised, phase 2 trial was undertaken in 24
      centres in six countries. 79 patients with non-Hodgkin lymphoma exclusively
      localised into the CNS, cranial nerves, or eyes, aged 18-75 years, and with
      Eastern Cooperative Oncology Group performance status of 3 or lower and
      measurable disease were centrally randomly assigned by computer to receive four
      courses of either methotrexate 3.5 g/m(2) on day 1 (n=40) or methotrexate 3.5
      g/m(2) on day 1 plus cytarabine 2 g/m(2) twice a day on days 2-3 (n=39). Both
      regimens were administered every 3 weeks and were followed by whole-brain
      irradiation. The primary endpoint was complete remission rate after chemotherapy.
      Analysis was by intention to treat. This study is registered with
      ClinicalTrials.gov, number NCT00210314. FINDINGS: All randomly assigned
      participants were analysed. After chemotherapy, seven patients given methotrexate
      and 18 given methotrexate plus cytarabine achieved a complete remission, with a
      complete remission rate of 18% (95% CI 6-30) and 46% (31-61), respectively,
      (p=0.006). Nine patients receiving methotrexate and nine receiving methotrexate
      plus cytarabine achieved a partial response, with an overall response rate of 40%
      (25-55) and 69% (55-83), respectively, (p=0.009). Grade 3-4 haematological
      toxicity was more common in the methotrexate plus cytarabine group than in the
      methotrexate group (36 [92%] vs six [15%]). Four patients died of toxic effects
      (three vs one). INTERPRETATION: In patients aged 75 years and younger with
      primary CNS lymphoma, the addition of high-dose cytarabine to high-dose
      methotrexate provides improved outcome with acceptable toxicity compared with
      high-dose methotrexate alone. FUNDING: Swiss Cancer League.

PMID- 19767091
TI  - Progress in primary CNS lymphoma.

PMID- 19767092
TI  - Dose-dense paclitaxel once a week in combination with carboplatin every 3 weeks
      for advanced ovarian cancer: a phase 3, open-label, randomised controlled trial.
AB  - BACKGROUND: Paclitaxel and carboplatin given every 3 weeks is standard treatment
      for advanced ovarian carcinoma. Attempts to improve patient survival by including
      other drugs have yielded disappointing results. We compared a conventional
      regimen of paclitaxel and carboplatin with a dose-dense weekly regimen in women
      with advanced ovarian cancer. METHODS: Patients with stage II to IV epithelial
      ovarian cancer, fallopian tube cancer, or primary peritoneal cancer were eligible
      for enrolment in this phase 3, open-label, randomised controlled trial at 85
      centres in Japan. Patients were randomly assigned by computer-generated
      randomisation sequence to receive six cycles of either paclitaxel (180 mg/m(2); 3
      h intravenous infusion) plus carboplatin (area under the curve [AUC] 6 mg/mL per
      min), given on day 1 of a 21-day cycle (conventional regimen; n=320), or dose
      dense paclitaxel (80 mg/m(2); 1-h intravenous infusion) given on days 1, 8, and
      15 plus carboplatin given on day 1 of a 21-day cycle (dose-dense regimen; n=317).
      The primary endpoint was progression-free survival. Analysis was by intention to
      treat (ITT). This trial is registered with ClinicalTrials.gov, number
      NCT00226915. FINDINGS: 631 of the 637 enrolled patients were eligible for
      treatment and were included in the ITT population (dose-dense regimen, n=312;
      conventional regimen, n=319). Median progression-free survival was longer in the
      dose-dense treatment group (28.0 months, 95% CI 22.3-35.4) than in the
      conventional treatment group (17.2 months, 15.7-21.1; hazard ratio [HR] 0.71; 95%
      CI 0.58-0.88; p=0.0015). Overall survival at 3 years was higher in the dose-dense
      regimen group (72.1%) than in the conventional treatment group (65.1%; HR 0.75,
      0.57-0.98; p=0.03). 165 patients assigned to the dose-dense regimen and 117
      assigned to the conventional regimen discontinued treatment early. Reasons for
      participant dropout were balanced between the groups, apart from withdrawal
      because of toxicity, which was higher in the dose-dense regimen group than in the
      conventional regimen group (n=113 vs n=69). The most common adverse event was
      neutropenia (dose-dense regimen, 286 [92%] of 312; conventional regimen, 276
      [88%] of 314). The frequency of grade 3 and 4 anaemia was higher in the dose
      dense treatment group (214 [69%]) than in the conventional treatment group (137
      [44%]; p<0.0001). The frequencies of other toxic effects were similar between
      groups. INTERPRETATION: Dose-dense weekly paclitaxel plus carboplatin improved
      survival compared with the conventional regimen and represents a new treatment
      option in women with advanced epithelial ovarian cancer. FUNDING: Bristol-Myers
      Squibb.

PMID- 19767090
TI  - Oestrogen plus progestin and lung cancer in postmenopausal women (Women's Health
      Initiative trial): a post-hoc analysis of a randomised controlled trial.
AB  - BACKGROUND: In the post-intervention period of the Women's Health Initiative
      (WHI) trial, women assigned to treatment with oestrogen plus progestin had a
      higher risk of cancer than did those assigned to placebo. Results also suggested
      that the combined hormone therapy might increase mortality from lung cancer. To
      assess whether such an association exists, we undertook a post-hoc analysis of
      lung cancers diagnosed in the trial over the entire follow-up period. METHODS:
      The WHI study was a randomised, double-blind, placebo-controlled trial undertaken
      in 40 centres in the USA. 16 608 postmenopausal women aged 50-79 years with an
      intact uterus were randomly assigned by a computerised, stratified, permuted
      block algorithm to receive a once-daily tablet of 0.625 mg conjugated equine
      oestrogen plus 2.5 mg medroxyprogesterone acetate (n=8506) or matching placebo
      (n=8102). We assessed incidence and mortality rates for all lung cancer, small
      cell lung cancer, and non-small-cell lung cancer by use of data from treatment
      and post-intervention follow-up periods. Analysis was by intention to treat. This
      study is registered with ClinicalTrials.gov, number NCT00000611. FINDINGS: After
      a mean of 5.6 years (SD 1.3) of treatment and 2.4 years (0.4) of additional
      follow-up, 109 women in the combined hormone therapy group had been diagnosed
      with lung cancer compared with 85 in the placebo group (incidence per year
      0.16%vs 0.13%; hazard ratio [HR] 1.23, 95% CI 0.92-1.63, p=0.16). 96 women
      assigned to combined therapy had non-small-cell lung cancer compared with 72
      assigned to placebo (0.14%vs 0.11%; HR 1.28, 0.94-1.73, p=0.12). More women died
      from lung cancer in the combined hormone therapy group than in the placebo group
      (73 vs 40 deaths; 0.11%vs 0.06%; HR 1.71, 1.16-2.52, p=0.01), mainly as a result
      of a higher number of deaths from non-small-cell lung cancer in the combined
      therapy group (62 vs 31 deaths; 0.09%vs 0.05%; HR 1.87, 1.22-2.88, p=0.004).
      Incidence and mortality rates of small-cell lung cancer were similar between
      groups. INTERPRETATION: Although treatment with oestrogen plus progestin in
      postmenopausal women did not increase incidence of lung cancer, it increased the
      number of deaths from lung cancer, in particular deaths from non-small-cell lung
      cancer. These findings should be incorporated into risk-benefit discussions with
      women considering combined hormone therapy, especially those with a high risk of
      lung cancer. FUNDING: National Heart, Lung and Blood Institute, National
      Institutes of Health.

PMID- 19767093
TI  - Maintenance pemetrexed plus best supportive care versus placebo plus best
      supportive care for non-small-cell lung cancer: a randomised, double-blind, phase
      3 study.
AB  - BACKGROUND: Several studies have shown the efficacy, tolerability, and ease of
      administration of pemetrexed-an antifolate antineoplastic agent-in patients with
      advanced non-small-cell lung cancer. We assessed pemetrexed as maintenance
      therapy in patients with this disease. METHODS: This randomised double-blind
      study was undertaken in 83 centres in 20 countries. 663 patients with stage IIIB
      or IV disease who had not progressed on four cycles of platinum-based
      chemotherapy were randomly assigned (2:1 ratio) to receive pemetrexed (500
      mg/m(2), day 1) plus best supportive care (n=441) or placebo plus best supportive
      care (n=222) in 21-day cycles until disease progression. Treatment was randomised
      with the Simon and Pocock minimisation method. Patients and investigators were
      masked to treatment. All patients received vitamin B(12), folic acid, and
      dexamethasone. The primary endpoint of progression-free survival and the
      secondary endpoint of overall survival were analysed by intention to treat. This
      study is registered with ClinicalTrials.gov, number NCT00102804. FINDINGS: All
      randomly assigned participants were analysed. Pemetrexed significantly improved
      progression-free survival (4.3 months [95% CI 4.1-4.7] vs 2.6 months [1.7-2.8];
      hazard ratio [HR] 0.50, 95% CI 0.42-0.61, p<0.0001) and overall survival (13.4
      months [11.9-15.9] vs 10.6 months [8.7-12.0]; HR 0.79, 0.65-0.95, p=0.012)
      compared with placebo. Treatment discontinuations due to drug-related toxic
      effects were higher in the pemetrexed group than in the placebo group (21 [5%] vs
      three [1%]). Drug-related grade three or higher toxic effects were higher with
      pemetrexed than with placebo (70 [16%] vs nine [4%]; p<0.0001), specifically
      fatigue (22 [5%] vs one [1%], p=0.001) and neutropenia (13 [3%] vs 0, p=0.006).
      No pemetrexed-related deaths occurred. Relatively fewer patients in the
      pemetrexed group than in the placebo group received systemic post-discontinuation
      therapy (227 [51%] vs 149 [67%]; p=0.0001). INTERPRETATION: Maintenance therapy
      with pemetrexed is well tolerated and offers improved progression-free and
      overall survival compared with placebo in patients with advanced non-small-cell
      lung cancer. FUNDING: Eli Lilly.

PMID- 19767094
TI  - Dose-dense chemotherapy in advanced ovarian cancer.

PMID- 19767095
TI  - Another nail in the coffin for hormone-replacement therapy?

PMID- 19767096
TI  - Maintenance therapy in non-small-cell lung cancer.

PMID- 19767097
TI  - The characteristics, biodistribution and bioavailability of a chitosan-based
      nanoparticulate system for the oral delivery of heparin.
AB  - Heparin is a potent anticoagulant; however, it is poorly absorbed in the
      gastrointestinal tract. In this study, we developed a nanoparticle (NP) system
      shelled with chitosan (CS) for oral delivery of heparin; the NPs were prepared by
      a simple ionic gelation method without chemically modifying heparin. The drug
      loading efficiency of NPs was nearly 100% because a significantly excess amount
      of CS was used for the CS/heparin complex preparation. The internal structure of
      the prepared NPs was examined by small angle X-ray scattering (SAXS). The
      obtained SAXS profiles suggest that the NPs are associated with a two-phase
      system and consist of the CS/heparin complex microdomains surrounded by the CS
      matrix. The stability of NPs in response to pH had a significant effect on their
      release of heparin. No significant anticoagulant activity was detected after oral
      administration of the free form heparin solution in a rat model, while
      administration of NPs orally was effective in the delivery of heparin into the
      blood stream; the absolute bioavailability was found to be 20.5%. The
      biodistribution of the drug carrier, (99m)Tc-labeled CS, in rats was studied by
      the single-photon emission computed tomography after oral administration of the
      radio-labeled NPs. No significant radioactivity was found in the internal organs,
      indicating a minimal absorption of CS into the systemic circulation. These
      results suggest that the NPs developed in the study can be employed as a
      potential carrier for oral delivery of heparin.

PMID- 19767098
TI  - The use of dentin matrix scaffold and dental follicle cells for dentin
      regeneration.
AB  - Scaffold and inductive microenvironment are the two most important factors for
      dentin regeneration. They have been addressed with hydroxyapatite, tricalcium
      phosphate, polyglycolic acid, calcined bovine bone, and collagen, among other
      things. However, as of yet, no scaffold and inductive microenvironment
      combination has been shown to contribute to the regeneration of complete and
      prefabricated-shaped dentin tissues that include dentin, predentin and
      odontoblasts. To test the supporting and inductive effects of treated dentin
      matrix (TDM) on complete and prefabricated-shaped dentin regeneration, dental
      follicle cells (DFCs) were seeded onto TDM and further incubated for 1 and 2
      weeks in vitro and for 2 and 4 weeks in vivo. The results show that in vitro, in
      addition to dentin sialoprotein (DSP) and dentin matrix protein 1 (DMP1)
      (regarded as identifying markers of odontoblasts), DFCs induced by TDM expressed
      osteocalcin, bone sialoprotein, type I collagen, osteopontin, osteonectin and
      alkaline phosphatase (all expressed by odontoblasts), and that complete and
      prefabricated-shaped dentin was successfully regenerated. Most importantly, it
      was found that in vivo TDM supports and induces regeneration of complete and
      prefabricated-shaped dentin, and regenerated dentin expresses DSP and DMP1, which
      are identifying dentin markers. Taken together, these results suggest that, for
      dentin regeneration, TDM is a suitable scaffold and inductive microenvironment
      and DFCs are a suitable cell type. The combination of TDM and DFCs may constitute
      a promising approach for future clinical dentin regeneration.

PMID- 19767099
TI  - Alternative splicing of hMLH1 in childhood acute lymphoblastic leukaemia and
      characterisation of the variably expressed Delta9/10 isoform as a dominant
      negative species.
AB  - Mismatch repair (MMR) deficiency is a common feature of acute lymphoblastic
      leukaemia (ALL) cell lines and in some cases is due to the mutations of hMLH1
      which affect mRNA splicing. Therefore, we have analysed alternative splicing of
      hMLH1 in a cohort of children with ALL. We show that alternative splicing of
      hMLH1 is highly variable in normal and leukaemic cells and can occur by exon
      skipping or by the use of an alternative splice site, both serving to down
      regulate the amount of full-length hMLH1 mRNA/protein produced. Aberrant splicing
      was found in one child with an aggressive leukaemia in which there was a
      predominant hMLH1Delta6 form and an associated loss of wild-type hMLH1 protein
      but this was not accompanied by microsatellite instability. Functional analysis
      of one of the most abundant spliced forms, hMLH1Delta9/10, was shown to have a
      significant dominant negative effect on the functionality of the MMR pathway but
      again was similarly expressed in ALL and normal cells.

PMID- 19767100
TI  - Transactivation of human osteopontin promoter by human T-cell leukemia virus type
      1-encoded Tax protein.
AB  - Osteopontin (OPN) is a cytokine that contributes substantially to the growth and
      metastasis in a wide spectrum of malignancies. We report here that OPN gene is
      transactivated by Tax protein of human T-cell leukemia virus type 1 (HTLV-1).
      Northern blot showed enhanced OPN gene expression in cells stably expressing Tax.
      Co-expression of Tax increased the reporter gene expression directed by OPN
      promoter. Tax-induced OPN activation was abrogated by treatment with LY294002
      (PI3K inhibitor) or co-transfection with AKT siRNA, suggesting PI3K/AKT pathway
      is involved in Tax-mediated transactivation. Reporter assay with deletion mutants
      showed that the 5'-partial sequence between -765 and -660 of the OPN promoter is
      the region responsive to Tax, and further, disrupting the AP-1 site within this
      region abolished the OPN induction by Tax, indicating that Tax activation of OPN
      promoter is likely mediated by AP-1 site. This study suggests that OPN is one of
      the downstream mediators of aberrantly activated PI3K/AKT signaling by Tax, which
      may partially contribute to HTLV-1-associated leukemogenesis.

PMID- 19767101
TI  - Child sexual abuse consequences in community samples of Latino and European
      American adolescents.
AB  - OBJECTIVE: Research investigating the impact of child sexual abuse (CSA) in
      community samples of adolescents has been limited. This study aims to identify
      sexual abuse among ethnically diverse high school adolescents of both genders and
      evaluate their psycho-emotional consequences. METHOD: Through the use of self
      report instruments, a sample of 223 Latino and European American 16-19-year-old
      high school students were identified as either victims of CSA or as nonabused.
      The emotional impact of sexual abuse was also investigated among these ethnically
      diverse adolescent males and females. RESULTS: Initial findings revealed that
      those adolescents who gave inconsistent responses to CSA assessments questions
      were much more similar in patterns of psychological distress to CSA victims
      compared to nonabused teenagers. Prevalence analyses revealed that females (45%)
      were nearly two times more likely to report CSA than males (24%). Latinos (44%)
      were significantly more likely to experience CSA compared to European Americans
      (27%), and Latinas (54%) had the highest prevalence overall. Other findings
      indicated substantial differences in type of perpetrator. While female victims of
      CSA identified male perpetrators in 91.9% of cases, male victims of CSA
      identified female perpetrators in 52.9% of cases. Consistent with past research,
      sexually abused adolescents reported significantly greater psychological distress
      than their nonabused peers, regardless of gender or ethnic group. Gender
      differences emerged with females reporting greater psychological symptoms, but
      these differences were substantially reduced when CSA was controlled. European
      Americans reported greater anxious arousal symptoms compared to Latinos.
      CONCLUSIONS: Our findings suggest that the prevalence of CSA among adolescents is
      higher than existing research has noted for both males and females and
      particularly higher for Latinos compared to European Americans. Perpetration by
      females upon males may also be higher than research has noted. Our findings also
      revealed many ethnic and gender similarities and fewer differences in the
      psychological impact and circumstances of sexual abuse in this diverse sample of
      adolescents. PRACTICE IMPLICATIONS: The high prevalence of CSA among adolescent
      males and particularly Latinas emphasize the need to intervene on a community
      level and with parents for both prevention and intervention regarding issues of
      sexual victimization. The numbers of female perpetrators, especially when boys
      are the targets of abuse, may be higher than previously imagined and thus must be
      assessed tactfully and thoroughly. This study found that adolescents who reported
      CSA inconsistently had similar symptoms as those with confirmed CSA and therefore
      warrant greater attention and more persistent intervention. When treating victims
      of CSA, the Trauma Symptom Inventory (TSI) is effective in identifying specific
      areas of emotional distress to treat in sexually abused ethnically diverse male
      and female adolescents. Culturally relevant prevention efforts are needed for
      ethnically diverse children of both genders.

PMID- 19767102
TI  - The association between osteocalcin gene polymorphism and dental fluorosis among
      children exposed to fluoride in People's Republic of China.
AB  - Excessive fluoride intake has been shown to affect dentin and cementum
      mineralization throughout life. Some studies indicated that a HindIII
      polymorphism, of osteocalcin (OC) gene, was associated with bone metabolism
      related diseases. Therefore, it is possible that the variation in OC genotypes
      will be associated with dental fluorosis (DF) status and/or serum caciotropic
      hormone level. A case-control study was conducted among children aged 8-12 years
      in Henan Province, PR China to investigate the association between dental
      fluorosis, serum calciotropic hormone level, and polymorphisms in the OC gene.
      HindIII polymorphism in OC gene was genotyped using the PCR-RFLP procedure. OC
      and calcitonin (CT) level in serum was detected using radioimmunoassay. No
      significant difference was observed for OC HindIII genotypes among the cases with
      dental fluorosis, the controls from endemic fluorosis area (EFA) and the controls
      from non-endemic fluorosis area (NEFA). A significant negative correlation was
      observed between serum calcium and OC level. No significant relationship was
      found between OC HindIII polymorphisms and the level of OC and CT. In conclusion,
      OC HindIII polymorphisms may not be a useful genetic marker for differential risk
      of dental fluorosis among children in PR China.

PMID- 19767103
TI  - Toxicity of acid mine pit lake water remediated with limestone and phosphorus.
AB  - Pit lakes are increasingly common worldwide and have potential to provide many
      benefits. However, lake water toxicity may require remediation before beneficial
      end uses can be realised. Three treatments to remediate AMD (pH approximately
      4.8) pit lake water containing elevated concentrations of Al and Zn from Collie,
      Western Australia were tested in mesocosms. Treatments were: (a) limestone
      neutralisation (L), (b) phosphorus amendment (P), and (c) combined limestone
      neutralisation and phosphorus amendment (L+P). Laboratory bioassays with
      Ceriodaphnia cf. dubia, Chlorella protothecoides and Tetrahymena thermophila
      assessed remediation. Limestone neutralisation increased pH and reduced heavy
      metal concentrations by 98% (Al) to 14% (Mg), removing toxicity to the three test
      species within 2 months. Phosphorus amendment removed toxicity after 6 months of
      treatment. However, phosphorus amendment to prior limestone neutralisation failed
      to reduce toxicity more than limestone neutralisation alone. Low concentrations
      of both phosphorus and nitrogen appear to limit phytoplankton population growth
      in all treatments.

PMID- 19767104
TI  - Ricin as a weapon of mass terror--separating fact from fiction.
AB  - In recent years there has been an increased concern regarding the potential use
      of chemical and biological weapons for mass urban terror. In particular, there
      are concerns that ricin could be employed as such an agent. This has been
      reinforced by recent high profile cases involving ricin, and its use during the
      cold war to assassinate a high profile communist dissident. Nevertheless, despite
      these events, does it deserve such a reputation? Ricin is clearly toxic, though
      its level of risk depends on the route of entry. By ingestion, the pathology of
      ricin is largely restricted to the gastrointestinal tract where it may cause
      mucosal injuries; with appropriate treatment, most patients will make a full
      recovery. As an agent of terror, it could be used to contaminate an urban water
      supply, with the intent of causing lethality in a large urban population.
      However, a substantial mass of pure ricin powder would be required. Such an
      exercise would be impossible to achieve covertly and would not guarantee success
      due to variables such as reticulation management, chlorination, mixing, bacterial
      degradation and ultra-violet light. By injection, ricin is lethal; however, while
      parenteral delivery is an ideal route for assassination, it is not realistic for
      an urban population. Dermal absorption of ricin has not been demonstrated. Ricin
      is also lethal by inhalation. Low doses can lead to progressive and diffuse
      pulmonary oedema with associated inflammation and necrosis of the alveolar
      pneumocytes. However, the risk of toxicity is dependent on the aerodynamic
      equivalent diameter (AED) of the ricin particles. The AED, which is an indicator
      of the aerodynamic behaviour of a particle, must be of sufficiently low micron
      size as to target the human alveoli and thereby cause major toxic effects. To
      target a large population would also necessitate a quantity of powder in excess
      of several metric tons. The technical and logistical skills required to formulate
      such a mass of powder to the required size is beyond the ability of terrorists
      who typically operate out of a kitchen in a small urban dwelling or in a small
      ill-equipped laboratory. Ricin as a toxin is deadly but as an agent of bioterror
      it is unsuitable and therefore does not deserve the press attention and
      subsequent public alarm that has been created.

PMID- 19767105
TI  - T cell extravasation: demonstration of synergy between activation of CXCR3 and
      the T cell receptor.
AB  - Endothelial cells present chemokines to T cells and can also stimulate the T cell
      antigen receptor by presentation of peptide-MHC antigen complexes. This study was
      designed to investigate the potential synergy between stimulation of the
      chemokine receptor CXCR3 and the human T cell receptor complex. Transendothelial
      T cell migration towards CXCL10 was modified by crosslinking CD3 immediately
      before addition to the endothelium. When resting endothelium was used, T cells
      which had been activated by crosslinking CD3 for only 1 min showed a significant
      reduction (p<0.0001) in migration when compared with untreated T cells. By
      contrast, endothelial cells which had been activated by stimulation with
      interferon-gamma and tumour necrosis factor-alpha supported a specific increase
      in the migration of activated T cells; this was most apparent after CD3 had been
      activated for 90 min (p<0.0001). The molecular basis for synergy between CXCR3
      and the T cell receptor complex was investigated by measurement of fluorescence
      resonance energy transfer. This showed that CXCL10 induced a close (<10 nm)
      spatial association between CXCR3 and the CD3epsilon subunit on the cell-surface.
      These data demonstrate that stimulation of both CXCR3 and the T cell receptor has
      the potential to enhance specifically both the proliferation and extravasation of
      specific T cells during episodes of local inflammation.

PMID- 19767106
TI  - L-ficolin (ficolin-2) insufficiency is associated with combined allergic and
      infectious respiratory disease in children.
AB  - We previously reported an association between relative L-ficolin deficiency and
      recurrent respiratory infections co-existing with allergic disorders in children.
      To confirm and extend this preliminary finding, we performed a prospective study
      on children of a similar age (mean 8.9 years) designed to establish whether the
      principal relationship was with infection or allergy. Serum L-ficolin values in
      healthy children were normally distributed with a mean value of 3838 ng/ml. L
      ficolin concentrations were generally lower in patients with asthma and/or
      allergic rhinitis with (mean 3413 ng/ml; p=0.02) or without (3512 ng/ml; p<0.07)
      respiratory infections, but not in patients with respiratory infections without
      allergic disease (3623 ng/ml; p=0.2). The lower average values in the group
      comprised of children with respiratory allergy and infections were largely due to
      a high proportion of very low values: 18.3% had values below 2150 ng/ml compared
      to only 5.5% of healthy controls (OR=3.9; p=0.01). This relationship was not
      apparent in the groups characterized by allergy without infection or infections
      without allergy. An association between mannan-binding lectin (MBL) insufficiency
      and recurrent respiratory infections was also confirmed. One of the patients was
      MASP-2 deficient, evidenced both by MASP2 genotyping and by lectin pathway
      activity measurement. In conclusion, L-ficolin may confer some protection from
      microorganisms that exacerbate allergic inflammation in the lung and its relative
      deficiency may contribute to enhanced susceptibility to respiratory infections.
      MBL insufficiency and MASP-2 deficiency are risk factors for recurrence of
      infections independently of allergic disease.

PMID- 19767107
TI  - Recombinant C3adesArg/acylation stimulating protein (ASP) is highly bioactive: a
      critical evaluation of C5L2 binding and 3T3-L1 adipocyte activation.
AB  - C5L2 is a recently identified receptor for C5a/C5adesArg, C3a and C3adesArg
      (ASP). C5a/C5adesArg bind with high affinity, with no identified activation. By
      contrast, some studies demonstrate C3a/ASP binding/activation to C5L2; others do
      not. Our aim is to critically evaluate ASP/C3adesArg-C5L2 binding and
      bioactivity. Cell-associated fluorescent-ASP (Fl-ASP) binding to C5L2 increased
      from transiently transfected<stably transfected<Fl-ASP-sorted C5L2-HEK for both
      human C5L2 and mouse C5L2. Transfected C5L2-CHO cells had similar results.
      Endogenous C5L2 expression increased from 3T3-L1 preadipocytes<3T3-L1
      adipocytes<primary mouse adipocytes. Non-transfected cells+/-Fl-ASP demonstrated
      background fluorescence only. In adherent C5L2-HEK (Fl-ASP sorted) and 3T3-L1
      cells, blocking with 10% fetal calf serum, protamine sulfate or ovalbumin
      prevented (125)I-ASP non-specific binding (NSB, no cells), while albumin
      increased NSB. Binding to non-transfected HEK was comparable to NSB. Optimal
      specific binding was obtained at 20 degrees C (vs. 4 degrees C) in PBS or serum
      free medium with K(d) 83.7+/-23.7 nM (C5L2-HEK), 66+/-15 nM (C5L2-CHO) and 76+/
      14.3 nM (3T3-L1 preadipocytes); (125)I-C5a binding had greater affinity. Fl-ASP
      C5L2 binding was comparable and concentration dependent (K(d) 31 nM (direct
      binding) and IC(50) 35 nM (competition binding) regardless of conditions).
      Recombinant ASP (rASP) produced in modified Escherichia coli Origami (DE3)
      (allowing folding and disulphide bridge formation), purified under non-denaturing
      conditions demonstrated 10x greater bioactivity vs. proteolytically derived
      plasma ASP for triglyceride synthesis and fatty acid uptake in 3T3-L1 adipocytes
      and preadipocytes while adipose tissue from C5L2 KO mice was non-responsive. rASP
      stimulation of adipocyte BODIPY-fatty acid uptake demonstrated EC(50) 115+/-93 nM
      and maximal stimulation of 413+/-33%, p<0.001. ASP binding has distinct
      characteristics that lead to C5L2 activation and increased bioactivity.

PMID- 19767108
TI  - Molecular cloning and functional characterization of avian interleukin-19.
AB  - The present study describes the cloning and functional characterization of avian
      interleukin (IL)-19, a cytokine that, in mammals, alters the balance of Th1 and
      Th2 cells in favor of the Th2 phenotype. The full-length avian IL-19 gene,
      located on chromosome 26, was amplified from LPS-stimulated chicken monocytes,
      and cloned into both prokaryotic (pET28a) and eukaryotic (pcDNA3.1) expression
      vectors. The confirmed avian IL-19 amino acid sequence has 66.5% homology with
      human and murine IL-19, with a predicted protein sequence of 176 amino acids.
      Analysis of avian IL-19 amino acid sequence showed six conserved, structurally
      relevant, cysteine residues as found in mammals, but only one N-glycosylation
      residue. The recombinant IL-19 (rChIL-19) expressed in the prokaryotic system was
      purified by Ni(+)-resin column followed by endotoxin removal. Using purified
      avian rChIL-19, expression of Th2 cytokines was measured in splenocytes using
      quantitative real-time PCR (qRT-PCR). In the presence of rChIL-19, expression
      levels of IL-4 and IL-13, as well as IL-10, were significantly increased after 6-
      and 12 h treatments. This was confirmed by treating splenocytes with supernatants
      from IL-19 transfected cells. Also, avian monocytes incubated with rChIL-19
      displayed increased expression of IL-1beta, IL-6, and IL-19. This study
      represents the first report for the cloning, expression, and functional
      characterization of avian IL-19. Taken together, avian IL-19 function seems to be
      conserved and similar to that of mammals and may play an important role in
      responses to intracellular poultry pathogens like bacteria and protozoa.

PMID- 19767109
TI  - Synthetic, structural and solution speciation studies on binary Al(III)
      (carboxy)phosphonate systems. Relevance to the neurotoxic potential of Al(III).
AB  - Efforts to delineate the interactions of neurotoxic Al(III) with low molecular
      mass substrates relevant to neurodegenerative processes, led to the investigation
      of the pH-specific synthetic chemistry of the binary Al(III)-[N-(phosphonomethyl)
      iminodiacetic acid] (Al-NTAP), Al(III)-[nitrilo-tris(methylene-phosphonic acid)]
      (Al-NTA3P), and Al(III)-[1-hydroxy ethylidene-1,1-diphosphonic acid] (Al-HEDP)
      systems, in correlation with solution speciation studies. Reaction of
      Al(NO(3))(3).9H(2)O with NTAP at pH 7.0 and 4.0 afforded the new species
      (CH(6)N(3))(4)[Al(2)(C(5)H(6)NPO(7))(2)(OH)(2)].8H(2)O (1) and
      (NH(4))(2)[Al(2)(C(5)H(6)NPO(7))(2)(H(2)O)(2)].4H(2)O (2), while reaction of
      Al(NO(3))(3).9H(2)O with NTA3P led to
      K(8)[Al(2)(C(3)H(6)NP(3)O(9))(2)(OH)(2)].20H(2)O (3). Complexes 1-3 were
      characterized by elemental analysis, FT-IR, (13)C, (31)P, (1)H NMR (for 1-2 solid
      state and solution NMR where feasible), and X-ray crystallography. The structures
      of 1-3 reveal the presence of uniquely defined dinuclear complexes of octahedral
      Al(III) bound to fully deprotonated phosphonate ligands, water and hydroxo
      moieties. The aqueous solution speciation studies on the aforementioned binary
      systems project a clear picture of the binary Al(III)-(carboxy)phosphonate
      interactions and species under variable pH-conditions and specific Al(III):ligand
      stoichiometry. The concurrent solid state and solution work (a) exemplifies
      essential structural and chemical attributes of soluble aqueous species,
      reflecting well-defined interactions of Al(III) with phosphosubstrates and (b)
      strengthens the potential linkage of neurotoxic Al(III) chemical reactivity
      toward O,N-containing (carboxy)phosphate-rich cellular targets.

PMID- 19767110
TI  - Up-regulation of integrin beta3 expression in porcine vascular endothelial cells
      cultured in vitro by classical swine fever virus.
AB  - Classical swine fever (CSF) caused by virulent strains of classical swine fever
      virus (CSFV) is a haemorrhagic disease of pigs, characterized by disseminated
      intravascular coagulation, thrombocytopenia and immunosuppression. The cell
      adhesion molecule, integrin beta3, plays a central role in maintaining and
      regulating vascular permeability. In view of the haemorrhagic pathology of the
      disease, the effect of CSFV infection on integrin beta3 expression was
      investigated using the swine umbilical vein endothelial cell (SUVEC) line, in
      conjunction with quantitative PCR and Western blotting techniques. Following
      infection, the expression levels of integrin beta3 were significantly up
      regulated along with corresponding transcription levels. The infected endothelial
      cells adhered onto immobilized extracellular matrix (ECM) with more extensive
      spreading than that of the control, and such interaction was strongly inhibited
      by an anti-integrin beta3 monoclonal antibody (mAb). This study revealed the up
      regulation of integrin beta3 in vascular endothelial cells by CSFV infection, and
      cell adhesion molecules of this kind possibly play an important role in the
      changes of haemostatic balance in haemorrhagic pathology of CSF.

PMID- 19767111
TI  - TNF-alpha and antibodies to periodontal bacteria discriminate between Alzheimer's
      disease patients and normal subjects.
AB  - The associations of inflammation/immune responses with clinical presentations of
      Alzheimer's disease (AD) remain unclear. We hypothesized that TNF-alpha and
      elevated antibodies to periodontal bacteria would be greater in AD compared to
      normal controls (NL) and their combination would aid clinical diagnosis of AD.
      Plasma TNF-alpha and antibodies against periodontal bacteria were elevated in AD
      patients compared with NL and independently associated with AD. The number of
      positive IgG to periodontal bacteria incremented the TNF-alpha classification of
      clinical AD and NL. This study shows that TNF-alpha and elevated numbers of
      antibodies against periodontal bacteria associate with AD and contribute to the
      AD diagnosis.

PMID- 19767112
TI  - Translational neuroimmunology: a joint meeting of the Israel Society of
      Neuroimmunology and the Italian Neuroimmunology Association. Conference review.

PMID- 19767113
TI  - Conscious sedation in pediatric speech endoscopy.
AB  - OBJECTIVE: Speech nasoendoscopy is one of the gold standards for evaluating
      velopharyngeal insufficiency. The vast majority of pediatric patients are able to
      tolerate this procedure within the clinic under local anesthetic. However, a
      select group of pediatric patients is unable to cooperate with the examination.
      Conscious sedation is commonly used in pediatrics to aid in patient tolerance and
      cooperating with selected procedures. Conscious sedation has never been reported
      in the literature for use in speech endoscopy. The purpose of this study is to
      describe a technique for performing sedated speech endoscopy and to review our
      experience with sedated speech endoscopy in a selected group of patients who were
      unable to cooperate with examination under local anesthesia alone. METHODS: A
      retrospective chart review was performed of pediatric patients between the ages
      of 2 and 15 who underwent conscious sedation for the speech nasoendoscopy. All
      examinations were performed at a tertiary care pediatric hospital. Sedation
      agent, tolerance of procedure, success of procedure, and complications associated
      with the procedure were recorded. RESULTS: Fifty-seven sedated speech endoscopies
      were evaluated. Adequate examinations were obtained in 93% of patients overall
      and 100% of the patients evaluated while sedated with nitrous oxide. Complication
      rates and post-endoscopy speech management are reported. CONCLUSIONS: Sedated
      speech endoscopy is a promising modality for evaluating velopharyngeal
      insufficiency in the pediatric population that may not otherwise be able to
      cooperate with examination in the clinic.

PMID- 19767114
TI  - A flock-tailored early warning system for low pathogenic avian influenza (LPAI)
      in commercial egg laying flocks.
AB  - The aim of this study was to develop and evaluate an early warning system (EWS)
      for commercial egg laying flocks to detect the subtle mortality and egg
      production changes that characterize low pathogenic avian influenza virus (LPAIV)
      infections. An EWS will create an alert when the recommended 'trigger point' is
      reached or exceeded. Previously used EWSs are based on fixed alert levels, while
      the proposed EWS customizes the alert level to each flock. While a fixed approach
      may be valid for highly pathogenic diseases, it results in a lower detection
      probability for low pathogenic diseases. The EWS was based on daily data
      collected from flocks affected by the 2000-2004 H6N2 LPAI epidemic in California.
      Three EWSs were evaluated: (1) EWS1, which is triggered when the observed
      mortality increase or production decrease exceeds more than "x" times the
      expected daily value (2.75-3.50 times the expected mortality), (2) EWS2, which is
      triggered when the observed mortality increase or production decrease exceeds
      more than "y" times during each of 2 consecutive days the expected daily values
      (1.75-2.15 times the expected mortality), and (3) a combination of the two. The
      EWSs were evaluated according to three parameters: detection delay (days) of a
      LPAI outbreak, false alerts (%) and outbreaks missed (%). Results showed that an
      egg production-based EWS added no benefit to a mortality-based system, mainly
      because H6N2 LPAI-related egg production decrease always occurred after increase
      in mortality. Combining the two EWSs resulted in a reduced detection delay and no
      missed outbreaks, but at the expense of a slight increase in the number of false
      alerts triggered. The system presented in this study also outperformed fixed EWSs
      in all three evaluated parameters. The proposed EWS, if used as part of a poultry
      cooperative program and combined with a rapid laboratory diagnosis, could be a
      useful tool in the detection and control of LPAI outbreaks and other poultry
      diseases. Built in a spreadsheet, the system could be inexpensively, easily and
      quickly incorporated into a commercial egg production farm decision support
      system. In addition, the proposed system could be quickly adjusted to changing
      epidemic situations, and easily customized to individual flocks.

PMID- 19767115
TI  - 18F-fluorocholine PET-guided target volume delineation techniques for partial
      prostate re-irradiation in local recurrent prostate cancer.
AB  - BACKGROUND AND PURPOSE: We evaluate the contribution of (18)F-choline PET/CT in
      the delineation of gross tumour volume (GTV) in local recurrent prostate cancer
      after initial irradiation using various PET image segmentation techniques.
      MATERIALS AND METHODS: Seventeen patients with local-only recurrent prostate
      cancer (median=5.7 years) after initial irradiation were included in the study.
      Rebiopsies were performed in 10 patients that confirmed the local recurrence.
      Following injection of 300 MBq of (18)F-fluorocholine, dynamic PET frames (3 min
      each) were reconstructed from the list-mode acquisition. Five PET image
      segmentation techniques were used to delineate the (18)F-choline-based GTVs.
      These included manual delineation of contours (GTV(man)) by two teams consisting
      of a radiation oncologist and a nuclear medicine physician each, a fixed
      threshold of 40% and 50% of the maximum signal intensity (GTV(40%) and GTV(50%)),
      signal-to-background ratio-based adaptive thresholding (GTV(SBR)), and a region
      growing (GTV(RG)) algorithm. Geographic mismatches between the GTVs were also
      assessed using overlap analysis. RESULTS: Inter-observer variability for manual
      delineation of GTVs was high but not statistically significant (p=0.459). In
      addition, the volumes and shapes of GTVs delineated using semi-automated
      techniques were significantly higher than those of GTVs defined manually.
      CONCLUSIONS: Semi-automated segmentation techniques for (18)F-choline PET-guided
      GTV delineation resulted in substantially higher GTVs compared to manual
      delineation and might replace the latter for determination of recurrent prostate
      cancer for partial prostate re-irradiation. The selection of the most appropriate
      segmentation algorithm still needs to be determined.

PMID- 19767116
TI  - An international review of patient safety measures in radiotherapy practice:
      Shafiq J, Barton M, Noble D, Lemer C, Donaldson LJ. Radiother Oncol. 2009
      Jul;92(1):15-21.

PMID- 19767117
TI  - Dose-volume histogram and dose-surface histogram analysis for skin reactions to
      carbon ion radiotherapy for bone and soft tissue sarcoma.
AB  - BACKGROUND AND PURPOSE: To evaluate the usefulness of the dose-volume histogram
      (DVH) and dose-surface histogram (DSH) as clinically relevant and available
      parameters that helped to identify bone and soft tissue sarcoma patients at risk
      of developing late skin reactions, including ulceration, when treated with carbon
      ion radiotherapy. MATERIALS AND METHODS: Thirty-five patients with bone and soft
      tissue sarcoma treated with carbon ion beams were studied. The clinical skin
      reactions were evaluated. Some pretreatment variables were compared with the
      grade of late skin reactions. RESULTS: Average DVH and DSH were established in
      accordance with the grading of the skin reactions. Prescribed dose, the
      difference in depths between the skin surface and the proximal extent of the
      tumor, and some DVH/DSH parameters were correlated with late skin reaction (> or
      = grade 3) according to univariate analysis. Furthermore, the area irradiated
      with over 60 GyE (S(60)>20 cm(2)) on DSH was the most important factor by
      multivariate analysis. CONCLUSIONS: The area irradiated with over 60 GyE
      (S(60)>20 cm(2)) on DSH was found to be a parameter for use as a predictor of
      late skin reactions.

PMID- 19767120
TI  - Assessment of hepatic insulin degradation, in normoglycemic hypertensive
      patients, by minimal modelling of standard intravenous glucose tolerance test
      data.
AB  - Role of hepatic insulin degradation in modulating insulin delivery to peripheral
      circulation, in insulin-resistant hypertensive patients, is not yet fully
      understood. This issue was investigated here by a novel application to
      hypertension of a previously proposed minimal modelling of insulin and C-peptide
      data, using population values for insulin and C-peptide kinetics parameters.
      Data, from frequently sampled intravenous glucose tolerance test (FSIGTT), were
      analysed in ten normoglycemic, hypertensive patients (H-group), compared with
      eight normoglycemic, normotensive subjects (N-group), matched for age, gender and
      body mass index. Minimal modelling of C-peptide and insulin data provided beta
      cell responsiveness to glucose perturbation (first, Phi(1), second, Phi(2), and
      basal, Phi(b), phase), insulin secretion rate, ISR(t) and total pre-hepatic
      insulin secretion, TIS, as well as insulin delivery rate, IDR(t), and total
      insulin delivery, TID, into plasma, over 5-h test. Instantaneous normalized
      hepatic insulin degradation rate was computed as HIDR(t)=1-[IDR(t)/ISR(t)]. In
      our H-group, insulin sensitivity, S(I), assessed by minimal model of glucose
      kinetics, showed a 56% reduction, which confirmed deterioration of insulin action
      in hypertension. This was associated with significant increase in Phi(1) (105%),
      TIS (55%) and TID (62%). No significant alterations were observed in other
      characteristic parameters of secretion and hepatic degradation of insulin, such
      that no significant difference was observed in HIDR(t) between our H and N
      groups. In conclusion, an increase of first phase and total insulin secretion
      occurring, in our H-group, in the presence of no alteration of hepatic insulin
      degradation, resulted in up-regulation of total insulin delivered to plasma (TID)
      for insulin-resistance compensation.

PMID- 19767119
TI  - Redundant roles for cJun-N-terminal kinase 1 and 2 in interleukin-1beta-mediated
      reduction and modification of murine hepatic nuclear retinoid X receptor alpha.
AB  - BACKGROUND/AIMS: Retinoid X receptor alpha (RXRalpha), the heterodimeric partner
      for multiple nuclear receptors (NRs), was shown to be an essential target for
      inflammation-induced cJun-N-terminal kinase (JNK) signaling in vitro. This study
      aimed to explore the role of hepatic JNK signaling and its effects on nuclear
      RXRalpha levels downstream of interleukin-1beta (IL-1beta) in vivo. METHODS:
      Effects of IL-1beta on hepatic NR-dependent gene expression, nuclear RXRalpha
      levels, and roles for individual JNK isoforms were studied in wild-type, Jnk1(-/
      ), and Jnk2(-/-) mice and in primary hepatocytes of each genotype. RESULTS: IL
      1beta administration showed a time-dependent reduction in expression of the
      hepatic NR-dependent genes Ntcp, Cyp7a1, Cyp8b1, Abcg5, Mrp2, and Mrp3. IL-1beta
      treatment for 1h activated JNK and resulted in both post-translational
      modification and reduction of nuclear RXRalpha. In wild-type primary hepatocytes,
      IL-1beta modified and reduced nuclear RXRalpha levels time dependently, which was
      prevented by chemical inhibition of JNK as well as by inhibition of proteasomal
      degradation. Individual absence of either JNK1 or JNK2 did not significantly
      influence the reduction or modification of hepatic nuclear RXRalpha by IL-1beta
      both in vivo and in primary hepatocytes. CONCLUSIONS: Functional redundancy
      exists for JNK1 and JNK2 in IL-1beta-mediated alterations of hepatic nuclear
      RXRalpha levels, stressing the importance of this pathway in mediating the
      hepatic response to inflammation.

PMID- 19767121
TI  - Herbivores, resources and risks: alternating regulation along primary
      environmental gradients in savannas.
AB  - Herbivores are regulated by predation under certain environmental conditions,
      whereas under others they are limited by forage abundance and nutritional
      quality. Whether top-down or bottom-up regulation prevails depends both on
      abiotic constraints on forage availability and body size, because size
      simultaneously affects the risk of predation of herbivores and their nutritional
      demands. Consequently, ecosystems composed of similar species can have different
      dynamics if they differ in resource supply. Here, we use large herbivore
      assemblages in African savanna ecosystems to develop a framework that connects
      environmental gradients and disturbance patterns with body size and trophic
      structure. This framework provides a model for understanding the functioning and
      diversity of ecosystems in general, and unifies how top-down and bottom-up
      mechanisms depend on common underlying environmental gradients.

PMID- 19767123
TI  - Laboratory analog and numerical study of groundwater flow and solute transport in
      a karst aquifer with conduit and matrix domains.
AB  - New mathematical and laboratory methods have been developed for simulating
      groundwater flow and solute transport in karst aquifers having conduits imbedded
      in a porous medium, such as limestone. The Stokes equations are used to model the
      flow in the conduits and the Darcy equation is used for the flow in the matrix.
      The Beavers-Joseph interface boundary conditions are adopted to describe the flow
      exchange at the interface boundary between the two domains. A laboratory analog
      is used to simulate the conduit and matrix domains of a karst aquifer. The
      conduit domain is located at the bottom of the transparent plexiglas laboratory
      analog and glass beads occupy the remaining space to represent the matrix domain.
      Water flows into and out of the two domains separately and each has its own
      supply and outflow reservoirs. Water and solute are exchanged through an
      interface between the two domains. Pressure transducers located within the matrix
      and conduit domains of the analog provide data that is processed and stored in
      digital format. Dye tracing experiments are recorded using time-lapse imaging.
      The data and images produced are analyzed by a spatial analysis program. The
      experiments provide not only hydraulic head distribution but also capture solute
      front images and mass exchange measurements between the conduit and matrix
      domains. In the experiment, we measure and record pressures, and quantify flow
      rates and solute transport. The results present a plausible argument that
      laboratory analogs can characterize groundwater water flow, solute transport, and
      mass exchange between the conduit and matrix domains in a karst aquifer. The
      analog validates the predictions of a numerical model and demonstrates the need
      of laboratory analogs to provide verification of proposed theories and the
      calibration of mathematical models.

PMID- 19767124
TI  - Characterizing sources of nitrate leaching from an irrigated dairy farm in Merced
      County, California.
AB  - Dairy farms comprise a complex landscape of groundwater pollution sources. The
      objective of our work is to develop a method to quantify nitrate leaching to
      shallow groundwater from different management units at dairy farms. Total nitrate
      loads are determined by the sequential calibration of a sub-regional scale and a
      farm-scale three-dimensional groundwater flow and transport model using
      observations at different spatial scales. These observations include local
      measurements of groundwater heads and nitrate concentrations in an extensive
      monitoring well network, providing data at a scale of a few meters and
      measurements of discharge rates and nitrate concentrations in a tile-drain
      network, providing data integrated across multiple farms. The various measurement
      scales are different from the spatial scales of the calibration parameters, which
      are the recharge and nitrogen leaching rates from individual management units.
      The calibration procedure offers a conceptual framework for using field
      measurements at different spatial scales to estimate recharge N concentrations at
      the management unit scale. It provides a map of spatially varying dairy farming
      impact on groundwater nitrogen. The method is applied to a dairy farm located in
      a relatively vulnerable hydrogeologic region in California. Potential sources
      within the dairy farm are divided into three categories, representing different
      manure management units: animal exercise yards and feeding areas (corrals),
      liquid manure holding ponds, and manure irrigated forage fields. Estimated
      average nitrogen leaching is 872 kg/ha/year, 807 kg/ha/year and 486 kg/ha/year
      for corrals, ponds and fields respectively. Results are applied to evaluate the
      accuracy of nitrogen mass balances often used by regulatory agencies to assess
      groundwater impacts. Calibrated leaching rates compare favorably to field and
      farm scale nitrogen mass balances. These data and interpretations provide a basis
      for developing improved management strategies.

PMID- 19767125
TI  - Overexpression of violaxanthin de-epoxidase gene alleviates photoinhibition of
      PSII and PSI in tomato during high light and chilling stress.
AB  - A tomato (Lycopersicon esculentum) violaxanthin de-epoxidase gene (LeVDE) was
      isolated. The deduced amino acid sequence of LeVDE showed high identities with
      violaxanthin de-epoxidase in other plant species. RNA gel blot analysis showed
      that the mRNA accumulation of LeVDE in the wild-type (WT) was regulated by
      diurnal rhythm and temperature. RNA and protein gel blot analyses confirmed that
      the sense LeVDE was transferred into the tomato genome and overexpressed under
      the control of 35S-CaMV. The ratio of (A+Z)/(V+A+Z) and the values of non
      photochemical quenching (NPQ) were higher in transgenic plants than those in WT
      under high light and chilling stress (4 degrees C). The net photosynthetic rate
      (Pn) decreased markedly in WT compared to transgenic lines under high light
      stress. The maximum quantum yield of primary photochemistry of PSII (Fv/Fm) in
      transgenic plants decreased more slowly during stresses and recovered faster than
      that in WT under optimal conditions. The oxidizable P700 in transgenic plants was
      higher than that in WT under chilling stress. These results suggest that
      overexpression of LeVDE increased the function of the xanthophyll cycle and
      alleviated photoinhibition of PSII and PSI in tomato during high light and
      chilling stress with low irradiance.

PMID- 19767126
TI  - An evaluation of the accuracy of emergency physician activation of the cardiac
      catheterization laboratory for patients with suspected ST-segment elevation
      myocardial infarction.
AB  - STUDY OBJECTIVE: Current recommendations indicate that emergency physicians
      should activate cardiac catheterization laboratory personnel by a single page for
      ST-segment elevation myocardial infarction (STEMI) patients. We assessed the
      accuracy of emergency physician cardiac catheterization laboratory activations,
      angiographic findings, outcomes, and treatment times among patients with and
      without STEMI. METHODS: We classified the appropriateness and outcomes of
      consecutive emergency physician STEMI pages between June 2006 and September 2008.
      Emergency physician activations of the cardiac catheterization laboratory were
      classified according to the findings of the initial ECG compared with cardiology
      interpretation for the presence of STEMI and presence of coronary disease.
      RESULTS: During a 27-month period, emergency physician activation of the cardiac
      catheterization laboratory occurred 249 times. There were 188 (76%) patients with
      a true STEMI, of whom 13 did not receive emergency angiography. Of the 37 (15%)
      patients who had ECG findings meeting STEMI criteria and who ultimately did not
      have myocardial necrosis and underwent emergency angiography, 12 had significant
      disease and 5 had revascularization performed. Eleven patients had ECGs
      concerning for but not meeting STEMI criteria; all had emergency angiography
      (n=11) or received a diagnosis of non-STEMI (n=6). Only 13 patients were
      considered as having received unnecessary cardiac catheterization laboratory
      activations (5.2%) in which emergency angiography was not performed and
      myocardial infarction was excluded. CONCLUSION: A significant number of emergency
      physician STEMI cardiac catheterization laboratory activations are for patients
      who did not meet standard STEMI criteria. However, most had ECG findings and
      symptoms that lead to emergency angiography, had significant disease, or were
      diagnosed with non-STEMI. Only a small percentage of patients received
      unnecessary cardiac catheterization laboratory activations. Our findings support
      current recommendations for emergency physician cardiac catheterization
      laboratory activation for potential STEMI patients.

PMID- 19767127
TI  - Enhancement of dentate gyrus neurogenesis, dendritic and synaptic plasticity and
      memory by a neurotrophic peptide.
AB  - Pharmacological enhancement of hippocampal neurogenesis is a therapeutic approach
      for improvement of cognition in learning and memory disorders such as Alzheimer's
      disease. Here we report the development of an 11-mer peptide that we designed
      based on a biologically active region of the ciliary neurotrophic factor. This
      peptide, Peptide 6, induced proliferation and increased survival and maturation
      of neural progenitor cells into neurons in the dentate gyrus of normal adult
      C57BL6 mice. Furthermore, Peptide 6 increased the MAP2 and synaptophysin
      immunoreactivity in the dentate gyrus. Thirty-day treatment of the mice with a
      slow release bolus of the peptide implanted subcutaneously improved reference
      memory of the mice in Morris water maze. Peptide 6 has a plasma half life of over
      6 h, is blood-brain barrier permeable, and acts by competitively inhibiting the
      leukemia inhibitory factor signaling. The fact that Peptide 6 is both neurogenic
      and neurotrophic and that this peptide is effective when given peripherally,
      demonstrates its potential for prevention and treatment of learning and memory
      disorders.

PMID- 19767128
TI  - Constitutive Ret signaling is protective for dopaminergic cell bodies but not for
      axonal terminals.
AB  - Ret is the canonical signaling receptor for glial cell line-derived neurotrophic
      factor (GDNF), which has been shown to have neuroprotective effects when
      administered prior to neurotoxic challenge. A missense Meth918Thr mutation causes
      the constitutive activation of Ret, resulting in multiple endocrine neoplasia
      type 2 B (MEN2B). To clarify the role of Ret signaling in neuroprotection, we
      studied the effects of the neurotoxins 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) and 6-hydroxydopamine (6-OHDA) on the dopaminergic
      system of mice carrying the MEN2B mutation. We found that MEN2B mice were
      significantly more resistant to nigral tyrosine hydroxylase (TH)-positive cell
      loss induced by unilateral striatal 6-OHDA than Wt mice. However, 6-OHDA caused
      profound dopamine (DA) depletion in the striatum of both MEN2B and Wt mice.
      Systemic MPTP caused similar DA depletion and a decrease in TH-immunostaining in
      the striatum of MEN2B and Wt mice. Neither neurotoxin induced a compensatory
      increase in striatal metabolite/DA ratios in the MEN2B mice, possibly
      contributing to an increased amphetamine-induced turning behavior observed in
      behavioral assessments of these mice. Thus, our data suggest that activated Ret
      protects DA cell bodies in the substantia nigra pars compacta, but does not
      protect DA axons in the striatum.

PMID- 19767129
TI  - [Actions to improve the methadone dispensing service in primary care].

PMID- 19767130
TI  - [Antifungal combination therapy in invasive fungal infections].
AB  - Invasive fungal infections (candidiasis, aspergillosis and cryptococcosis) are
      major complications in immunocompromised patients and account for high morbidity
      and mortality. Guidelines on first-line therapy of invasive fungal infections are
      based on randomised clinical trials or experts' guidelines and include
      essentially single antifungal therapies, except for cryptococcosis. However, the
      severe prognosis of these infections raises the interest of antifungal
      associations, in first line or second-line therapy, and many experimental data
      have been published on this issue. In humans, amphotericin B plus flucytosine
      combination therapy in cryptococcal meningitis has been largely validated,
      especially in HIV-infected patients. Also, a few studies demonstrated that the
      combination of fluconazole plus amphotericin B in candidiasis is not antagonistic
      and that caspofungin plus polyene or caspofungin plus azole combinations may be
      beneficial in invasive aspergillosis. Randomised studies are necessary to confirm
      these data. A study assessing anidulafungin plus voriconazole association in
      aspergillosis is oncoming.

PMID- 19767131
TI  - Literacy and numeracy for pre-registration nursing programmes: 1. An innovative
      way to widen access to nursing programmes for students without formal
      qualifications by enabling them to give evidence of their literacy and numeracy
      skills.
AB  - The Nursing and Midwifery Council (NMC, 2003) removed standard entry criteria for
      nursing programmes and asked Higher Education Institutions (HEIs) to consider the
      literacy and numeracy skills of prospective students. This triggered admissions
      staff within a Faculty of Health to consider ways of attracting people with the
      right skills but not the qualifications to prove it. It is important to encourage
      a wide range of people into nursing to meet the demands of strategic plans and
      policy, as well as to ensure the nursing profession reflects the diverse client
      groups it serves. Removing standard entry criteria and the widening participation
      agenda gave an ideal opportunity to try something new. A course entitled
      'Portfolio of Evidence for Entry to Level 1 Study' was developed within the
      Faculty of Health at Staffordshire University to enable potential nursing
      students without standard entry qualifications to demonstrate their skills in
      numeracy and literacy. This paper reports on the background to this course and
      its success for three student cohorts (over an 18 month period) who have
      completed their first year of pre-registration nursing. The methodology employed
      is descriptive, qualitative analysis, comparing portfolio and standard entry
      students' assignment results.

PMID- 19767132
TI  - "All-on-four" concept and immediate loading for simultaneous rehabilitation of
      the atrophic maxilla and mandible with conventional and zygomatic implants.
AB  - We report the simultaneous rehabilitation of an edentulous patient with a hybrid
      (zygomatic and conventional implants) all-on-four implant-supported prosthesis
      for the maxilla and a standard (conventional implants) all-on-four implant
      supported prosthesis for the mandible. The transfer impression was made with a
      multifunctional guide and the upper and lower prostheses were placed 24h
      postoperatively. Clinical and radiographic examinations showed no infection or
      bony resorption 2 years later. Simultaneous maxillary and mandibular
      rehabilitation with all-on-four immediate loading is a viable, fast and effective
      option for edentulous patients.

PMID- 19767133
TI  - Measurements of Cd, Cu, Pb and Zn in the lower reaches of major Eurasian arctic
      rivers using trace metal clean techniques.
AB  - Concentrations of dissolved and particulate Cd, Cu, Pb and Zn were determined in
      samples collected in summer 1998 from the lower reaches of six major Eurasian
      arctic rivers: the Onega, Severnaya Dvina, Mezen, Pechora, Ob and Yenisey. These
      data comprise some of the earliest measurements of trace metals in Eurasian
      arctic rivers above the estuaries using recognized clean techniques. Significant
      (alpha = 0.05) differences were observed among mean concentrations of particulate
      metals in the individual rivers (F < or = 0.006), with highest levels overall
      observed in the Severnaya Dvina and Yenisey. No significant differences were
      observed among mean concentrations of dissolved metals in the individual rivers
      (F = 0.10-0.84). Contributions from anthropogenic sources are suggested by
      comparison of trace metal ratios in the samples to crustal abundances. These
      results establish a baseline for assessing future responses of Eurasian arctic
      river systems to climate-related environmental changes and shifting patterns of
      pollutant discharge.

PMID- 19767134
TI  - Sun light degradation of 4-chloroaniline in waters and its effect on toxicity. A
      high performance liquid chromatography - Diode array - Tandem mass spectrometry
      study.
AB  - This paper studies the degradation reactions that 4-chloroaniline can naturally
      undergo in waters for the action of sun light. 10.00 mg L(-1) 4-chloroaniline
      aqueous solution, without any addition of organic solvent, are undergone to
      photoirradiation under conditions that simulate sun light. The degradation
      pathway, followed by HPLC-DAD-MS/MS methods, is complex since the pollutant gives
      rise to many photoproducts: the predominant species are characterized by m/z
      values of 217 (P5) and 218 (P6) and are compatible with dimeric structures of 4
      chloroaniline. Vibrio fischeri tests indicate that the photoproducts of 4
      chloroaniline are characterized by a toxicity level significantly greater than
      the precursor.

PMID- 19767135
TI  - The role of health insurance in explaining immigrant versus non-immigrant
      disparities in access to health care: comparing the United States to Canada.
AB  - Using a cross-national comparative approach, we examined the influence of health
      insurance on U.S. immigrant versus non-immigrant disparities in access to primary
      health care. With data from the 2002/2003 Joint Canada/United States Survey of
      Health, we gathered evidence using three approaches: 1) we compared health care
      access among insured and uninsured immigrants and non-immigrants within the U.S.;
      2) we contrasted these results with health care access disparities between
      immigrants and non-immigrants in Canada, a country with universal health care;
      and 3) we conducted a novel direct comparison of health care access among insured
      and uninsured U.S. immigrants with Canadian immigrants (all of whom are insured).
      Outcomes investigated were self-reported unmet medical needs and lack of a
      regular doctor. Logistic regression models controlled for age, sex, nonwhite
      status, marital status, education, employment, and self-rated health. In the
      U.S., odds of unmet medical needs of insured immigrants were similar to those of
      insured non-immigrants but far greater for uninsured immigrants. The effect of
      health insurance was even more striking for lack of regular doctor. Within
      Canada, disparities between immigrants and non-immigrants were similar in
      magnitude to disparities seen among insured Americans. For both outcomes, direct
      comparisons of U.S. and Canada revealed significant differences between uninsured
      American immigrants and Canadian immigrants, but not between insured Americans
      and Canadians, stratified by nativity. Findings suggest health care insurance is
      a critical cause of differences between immigrants and non-immigrants in access
      to primary care, lending robust support for the expansion of health insurance
      coverage in the U.S. This study also highlights the usefulness of cross-national
      comparisons for establishing alternative counterfactuals in studies of
      disparities in health and health care.

PMID- 19767136
TI  - Mortality effects of average education in current and earlier municipality of
      residence among internal migrants, net of their own education.
AB  - Many researchers have shown an association between a person's health or mortality
      and the socio-economic resources in the community, net of the person's own
      resources. The focus has typically been on the current community of residence or
      one where the person lived a few years earlier. Only a few authors have tried to
      establish whether there is an additional effect of earlier community exposures,
      and they have not made a distinction between migrants and non-migrants, which
      there are good reasons to do. The results from these earlier investigations have
      been rather mixed. In the present study, a discrete-time hazard model for
      mortality between ages of 60-89 over the period 1991-2002 was estimated from
      register data that included the entire Norwegian population. For each person, and
      for each of these years, municipalities of residence during the previous 20 years
      were known. There was also information on each person's educational level. For
      the relevant years and each of the 433 municipalities, measures of average
      education in the population were constructed by aggregating over the individual
      data. The analysis was focused on the subgroup who had moved across a
      municipality border only once during the previous 20 years, among whom there were
      29,843 deaths during 839,113 person-years of follow-up. The population sizes of
      the municipalities were included as control variables. Among those who had moved
      within the last 10 years, the current socio-economic context was not important
      for mortality. The earlier context had an effect, but this was restricted to men.
      Those who had lived longer in the current municipality of residence were
      influenced only by the average education in that municipality. The findings
      support the idea that neighbourhood socio-economic effects need some time to
      build up, and that they do not dissipate soon after the person has moved to a new
      environment.

PMID- 19767137
TI  - Socioeconomic inequalities in physical and mental functioning of British,
      Finnish, and Japanese civil servants: role of job demand, control, and work
      hours.
AB  - This study aims to evaluate whether the pattern of socioeconomic inequalities in
      physical and mental functioning as measured by the Short Form 36 (SF-36) differs
      among employees in Britain, Finland, and Japan and whether work characteristics
      contribute to some of the health inequalities. The participants were 7340 (5122
      men and 2218 women) British employees, 2297 (1638 men and 659 women) Japanese
      employees, and 8164 (1649 men and 6515 women) Finnish employees. All the
      participants were civil servants aged 40-60 years. Both male and female low grade
      employees had poor physical functioning in all cohorts. British and Japanese male
      low grade employees tended to have poor mental functioning but the associations
      were significant only for Japanese men. No consistent employment-grade
      differences in mental functioning were observed among British and Japanese women.
      Among Finnish men and women, high grade employees had poor mental functioning. In
      all cohorts, high grade employees had high control, high demands and long work
      hours. The grade differences in poor physical functioning and disadvantaged work
      characteristics among non-manual workers were somewhat smaller in the Finnish
      cohort than in the British and Japanese cohorts. Low control, high demands, and
      both short and long work hours were associated with poor functioning. When work
      characteristics were adjusted for, the socioeconomic differences in poor
      functioning were mildly attenuated in men, but the differences increased slightly
      in women. This study reconfirms the generally observed pattern of socioeconomic
      inequalities in health for physical functioning but not for mental functioning.
      The role of work characteristics in the relationship between socioeconomic status
      and health differed between men and women but was modest overall. We suggest that
      these differences in the pattern and magnitude of grade differences in work
      characteristics and health among the 3 cohorts may be attributable to the
      different welfare regimes among the 3 countries.

PMID- 19767138
TI  - Inexact rough-interval two-stage stochastic programming for conjunctive water
      allocation problems.
AB  - An inexact rough-interval two-stage stochastic programming (IRTSP) method is
      developed for conjunctive water allocation problems. Rough intervals (RIs), as a
      particular case of rough sets, are introduced into the modeling framework to
      tackle dual-layer information provided by decision makers. Through embeding upper
      and lower approximation intervals, rough intervals are capable of reflecting
      complex parameters with the most reliable and possible variation ranges being
      identified. An interactive solution method is also derived. A conjunctive water
      allocation system is then structured for characterizing the proposed model.
      Solutions indicate a detailed optimal allocation scheme with a rough-interval
      form; a total of [[1048.83, 2078.29]:[1482.26, 2020.60]] would be obtained under
      the pre-regulated inputs. Comparisons of the proposed model to a conventional and
      an interval two-stage stochastic programming model are also conducted. The
      results indicate that the optimal objective function values of TSP and ITSP
      always fall into the range of f(opt)(+/-(UAI)), while they are sometimes out of
      the range of f(opt)(+/-(LAI)); the optimal solutions of decision variables also
      present this feature. This implies the reliability of IRTSP in handling
      conjunctive water allocation problems.

PMID- 19767139
TI  - Analysis of elastographic and B-mode features at sonoelastography for breast
      tumor classification.
AB  - The purpose of this study was to evaluate the accuracy of neural network analysis
      of elastographic features at sonoelastography for the classification of biopsy
      proved benign and malignant breast tumors. Sonoelastography of 181 solid breast
      masses (113 benign and 68 malignant tumors) was performed for 181 patients (mean
      age, 47 years; range, 24-75 years). After the manual segmentation of the tumors,
      five elastographic features (strain difference, strain ratio, mean, median and
      mode) and six B-mode features (orientation, undulation, angularity, average
      gradient, gradient variance and intensity variance) were computed. A neural
      network was used to classify tumors by the use of these features. The Student's t
      test and receiver operating characteristic (ROC) curve analysis were used for
      statistical analysis. Area under ROC curve (Az) values of the three elastographic
      features- mean (0.87), median (0.86) and mode (0.83)-were significantly higher
      than the Az values for the six B-mode features (0.54-0.69) (p < 0.01). Accuracy,
      sensitivity, specificity and Az of the neural network for the classification of
      solid breast tumors were 86.2% (156/181), 83.8% (57/68), 87.6% (99/113) and 0.84
      for the elastographic features, respectively, and 82.3% (149/181), 70.6% (48/68),
      89.4% (101/113) and 0.78 for the B-mode features, respectively, and 90.6%
      (164/181), 95.6% (65/68), 87.6% (99/113) and 0.92 for the combination of the
      elastographic and B-mode features, respectively. We conclude that
      sonoelastographic images and neural network analysis of features has the
      potential to increase the accuracy of the use of ultrasound for the
      classification of benign and malignant breast tumors.

PMID- 19767140
TI  - Re: Christopher R. Chapple, Vik Khullar, Zahava Gabriel, et al. The effects of
      antimuscarinic treatments in overactive bladder: an update of a systematic review
      and meta-analysis. Eur urol 2008;54:543-62.

PMID- 19767141
TI  - Endoscopic management of hydrocephalus due to neurocysticercosis.
AB  - OBJECTIVE: Hydrocephalus due to neurocysticercosis usually shows poor prognosis
      and shunt failure is a common complication. Neuroendoscopy has been suggested as
      treatment, but the indications remain unclear. METHODS: A cohort of patients with
      clinical/radiological diagnosis of hydrocephalus due to NCC, treated between
      January 2002 and September 2006, were the subjects of the study. We excluded
      patients with tumors or those in whom diagnosis was not confirmed
      (histology/positive ELISA in CSF). Neuroendoscopy was offered as the first line
      of treatment. Shunt failure rate and Karnofsky index at 12 months were assessed.
      RESULTS: Eighty-six patients (47 male) with a median age of 38 (9-79) were
      included in the study. Of them, 36.1% had a shunt before endoscopy and 97.7% had
      a Karnofsky index <80. We did not find the parasite in 18.6%, extraction was
      achieved in 79%, and in 87.2% an endoscopic third ventriculostomy (ETV) was
      performed. The median follow-up time was 43 months (1-72). Shunt failure was seen
      in 6.6% of patients with ETV in comparison to 27.2% in those without ETV. A
      hazard ratio of 0.22 (95% CI, 0.05-0.93) for shunt failure after ETV was
      calculated. At 12 months, 20.9% had a Karnofsky index <80. CONCLUSION: Early
      extraction of parasite plus ETV might allow improving outcome and reducing shunt
      failure. Limitation of inflammatory stimulation by parasite antigens and
      improvement of CSF dynamics could be an explanation for these findings.

PMID- 19767142
TI  - Remediation of heavy metal contaminated soil washing residues with amino
      polycarboxylic acids.
AB  - Removal of Cu, Pb, and Zn by the action of the two biodegradable chelating agents
      [S,S]-ethylenediaminedisuccinic acid (EDDS) and methylglycinediacetic acid
      (MGDA), as well as citric acid, was tested. Three soil samples, which had
      previously been treated by conventional soil washing (water), were utilized in
      the leaching tests. Experiments were performed in batches (0.3 kg-scale) and with
      a WTC-mixer system (Water Treatment Construction, 10 kg-scale). EDDS and MGDA
      were most often equally efficient in removing Cu, Pb, and Zn after 10-60 min.
      Nonetheless, after 10d, there were occasionally significant differences in
      extraction efficiencies. Extraction with citric acid was generally less
      efficient, however equal for Zn (mainly) after 10d. Metal removal was similar in
      batch and WTC-mixer systems, which indicates that a dynamic mixer system could be
      used in full-scale. Use of biodegradable amino polycarboxylic acids for metal
      removal, as a second step after soil washing, would release most remaining metals
      (Cu, Pb and Zn) from the present soils, however only after long leaching time.
      Thus, a full-scale procedure, based on enhanced metal leaching by amino
      polycarboxylic acids from soil of the present kind, would require a pre-leaching
      step lasting several days in order to be efficient.

PMID- 19767143
TI  - Alkali-activated complex binders from class C fly ash and Ca-containing
      admixtures.
AB  - Processes that maximize utilization of industrial solid wastes are greatly
      needed. Sodium hydroxide and sodium silicate solution were used to create alkali
      activated complex binders (AACBs) from class C fly ash (CFA) and other Ca
      containing admixtures including Portland cement (PC), flue gas desulfurization
      gypsum (FGDG), and water treatment residual (WTR). Specimens made only from CFA
      (CFA100), or the same fly ash mixed with 40 wt% PC (CFA60-PC40), with 10 wt% FGDG
      (CFA90-FGDG10), or with 10 wt% WTR (CFA90-WTR10) had better mechanical
      performance compared to binders using other mix ratios. The maximum compressive
      strength of specimens reached 80.0 MPa. Geopolymeric gel, sodium polysilicate
      zeolite, and hydrated products coexist when AACB reactions occur. Ca from CFA,
      PC, and WTR precipitated as Ca(OH)(2), bonded in geopolymers to obtain charge
      balance, or reacted with dissolved silicate and aluminate species to form calcium
      silicate hydrate (C-S-H) gel. However, Ca from FGDG probably reacted with
      dissolved silicate and aluminate species to form ettringite. Utilization of CFA
      and Ca-containing admixtures in AACB is feasible. These binders may be widely
      utilized in various applications such as in building materials and for
      solidification/stabilization of other wastes, thus making the wastes more
      environmentally benign.

PMID- 19767144
TI  - A newly found cadmium accumulator--Malva sinensis Cavan.
AB  - Screening hyperaccumulators and accumulators is a key step in the
      phytoremediation of soils contaminated by heavy metals. A pot experiment was
      conducted involving a soil Cd concentration gradient (0, 50, 75, 100, 125, 150,
      175, and 200 mg kg(-1)) to determine if Malva sinensis Cavan. from two lead-zinc
      mines in Kangding and Yajiang in western Sichuan, China, is a Cd
      hyperaccumulator. The highest Cd concentrations in plant shoots from Kangding and
      Yajiang were 154.30 and 122.77 mg kg(-1), respectively, at a soil Cd
      concentration of 200 mg kg(-1). The largest amounts of accumulation in plant
      shoots from Kangding and Yajiang were 700.5 and 1403.2 microg pot(-1),
      respectively. The bioconcentration factors in shoots were 0.53-1.03 for Kangding
      and 0.69-1.25 for Yajiang. Moreover, all translocation factors of plants from the
      two sites were over 1.0. Therefore, M. sinensis can be classified as a Cd
      accumulator or non-standard Cd-hyperaccumulator.

PMID- 19767145
TI  - Peripheral NMDA receptors revisited - Hope floats.

PMID- 19767146
TI  - Somatosensory profiles in subgroups of patients with myogenic temporomandibular
      disorders and Fibromyalgia Syndrome.
AB  - Some patients with myofascial pain from temporomandibular disorders (TMD) report
      pain in extra-trigeminal body regions. Our aim was to distinguish TMD as regional
      musculoskeletal pain syndrome (n=23) from a widespread pain syndrome (FMS; n=18)
      based on patients' tender point scores, pain drawings and quantitative sensory
      testing (QST) profiles. Referenced to 18 age- and gender-matched healthy subjects
      significant group differences for cold, pressure and pinprick pain thresholds,
      suprathreshold pinprick sensitivity and mechanical detection thresholds were
      found. Pain sensitivity in TMD patients ranged between those of FMS patients and
      healthy controls. The group of TMD patients was inhomogeneous with respect to
      their tender point count with an insensitive group (n=12) resembling healthy
      controls and a sensitive TMD group (n=9) resembling FMS patients. Nevertheless
      sensitive TMD patients did not fulfil diagnostic criteria for FMS in regard to
      widespread pain as shown by their pain drawings. TMD subgroups did not differ
      with respect to psychological parameters. The sensitive subgroup was more
      sensitive compared to healthy controls and to insensitive TMD patients in regard
      to their QST profile over all test areas as well as to their tenderness over
      orofacial muscles and trigeminal foramina. However, sensitive TMD patients had a
      short pain duration arguing against a transition from TMD to FMS over time. Data
      rather suggest an overlap in pathophysiology with FMS, e.g. a disturbance of
      central pain processing, in this subgroup of TMD patients. Those patients could
      be identified on the basis of their tender point count as an easy practicable
      screening tool.

PMID- 19767147
TI  - Reliability and validity of observer ratings of pain using the visual analog
      scale (VAS) in infants undergoing immunization injections.
AB  - We tested the reliability and validity of observer-rated pain in infants
      undergoing immunization using the visual analog scale (VAS). Pain was assessed in
      real time and later, from videotapes, in 120 1-year-old infants participating in
      a double-blind randomized controlled trial of amethocaine vs. placebo.
      Altogether, 2 (1 physician, 1 non-physician) of 4 raters [2 physicians, 2 non
      physicians (nurse and graduate student)] independently assessed baseline and
      vaccine injection pain using a 100mm unmarked VAS line. Intra- and inter-rater
      reliability, assessed using the intra-class correlation coefficient (ICC), ranged
      from 0.69 to 0.91 and 0.55 to 0.97, respectively. Bland-Altman plots demonstrated
      no evidence of bias between real time and video assessments. When scores were
      dichotomized into 2 groups (no pain and pain) using a cut-off of >or=30mm, intra
      rater reliability ranged from 0.35 to 0.92. The percent of scores deviating by
      >20mm was 4.5-14.29%. Criterion validity was demonstrated by correlations between
      the VAS and Modified Behavioural Pain Scale, a validated observational measure;
      (rho: 0.81-0.94). Injection scores were lower in the amethocaine group, when
      comparing difference (baseline-injection) or dichotomized scores; significance
      (p<0.036) was achieved for non-physician scores, but not physician scores.
      Together, these results provide initial support for the VAS as an outcome measure
      for acute procedural pain in infants. However, different conclusions may be
      reached about the effectiveness of analgesic interventions depending on the
      rater. Sources of variability include use of multiple raters, rater focus
      (procedure vs. child) and experience level.

PMID- 19767148
TI  - Medical evaluation of children with chronic abdominal pain: impact of diagnosis,
      physician practice orientation, and maternal trait anxiety on mothers' responses
      to the evaluation.
AB  - This study examined the effects of diagnosis (functional versus organic),
      physician practice orientation (biomedical versus biopsychosocial), and maternal
      trait anxiety (high versus low) on mothers' responses to a child's medical
      evaluation for chronic abdominal pain. Mothers selected for high (n=80) and low
      (n=80) trait anxiety imagined that they were the mother of a child with chronic
      abdominal pain described in a vignette. They completed questionnaires assessing
      their negative affect and pain catastrophizing. Next, mothers were randomly
      assigned to view one of four video vignettes of a physician-actor reporting
      results of the child's medical evaluation. Vignettes varied by diagnosis
      (functional versus organic) and physician practice orientation (biomedical versus
      biopsychosocial). Following presentation of the vignettes, baseline
      questionnaires were re-administered and mothers rated their satisfaction with the
      physician. Results indicated that mothers in all conditions reported reduced
      distress pre- to post-vignette; however, the degree of the reduction differed as
      a function of diagnosis, presentation, and anxiety. Mothers reported more post
      vignette negative affect, pain catastrophizing, and dissatisfaction with the
      physician when the physician presented a functional rather than an organic
      diagnosis. These effects were significantly greater for mothers with high trait
      anxiety who received a functional diagnosis presented by a physician with a
      biomedical orientation than for mothers in any other condition. Anxious mothers
      of children evaluated for chronic abdominal pain may be less distressed and more
      satisfied when a functional diagnosis is delivered by a physician with a
      biopsychosocial rather than a biomedical orientation.

PMID- 19767150
TI  - Focal injection of vancomycin combined with surgical debridement-dermatoplasty in
      the treatment of pseudo-epitheliomatous granuloma.
AB  - BACKGROUND: Pseudo-epitheliomatous granuloma (PEG) can occur in some small skin
      wounds with secondary infections resulting from improper treatments. It is
      difficult to heal and can easily relapse. OBJECTIVES: This study explores the
      clinical and pathological characteristics of PEG and effective treatments.
      PATIENTS AND METHODS: Tissue specimens of PEG obtained from 11 patients (age
      range: 2-67 years) were sent for microbial examination and histological
      observation. The local lesions were treated by focal injection of vancomycin
      combined with surgical debridement-dermatoplasty. RESULTS: The diagnosis of PEG
      was based on histological examination, which revealed long epithelial peduncle
      encapsulated granulation tissue-like honeycomb in which more vessels,
      macrophages, lymphocytes and mast cells and less extracellular matrix were
      distributed. Bacteria such as Staphylococcus aureus, Bacillus pyocyaneus,
      ethylene-type Streptococcus, stool Streptococcus and F-citric acid Bacillus were
      found in the microbial culture of the specimens. They were tolerant to celbenin
      but sensitive to vancomycin. PEG could be cured by focal application of
      vancomycin combined with free skin or skin flap after thorough debridement. The
      relapse of PEG could be prevented by the therapy. CONCLUSION: Focal injection of
      vancomycin combined with surgical debridement-dermatoplasty is an effective
      therapy for PEG.

PMID- 19767149
TI  - A-kinase anchoring protein 150 controls protein kinase C-mediated phosphorylation
      and sensitization of TRPV1.
AB  - Post-translational modifications on various receptor proteins have significant
      effects on receptor activation. For the Transient Receptor Potential family V
      type 1 (TRPV1) receptor, phosphorylation of certain serine/threonine amino acid
      residues sensitizes the receptor to activation by capsaicin and heat. Although
      Protein Kinase C (PKC) phosphorylates TRPV1 on certain serine/threonine residues,
      it is not completely understood how PKC functionally associates with TRPV1.
      Recent studies have reported that the A-kinase Anchoring Protein 150 (AKAP150)
      mediates PKA phosphorylation of TRPV1 in several nociceptive models. Here, we
      demonstrate that AKAP150 also mediates PKC-directed phosphorylation and
      sensitization of TRPV1. In cultured rat trigeminal ganglia, immunocytochemical
      analyses demonstrate co-localization of AKAP150 and PKC isoforms alpha, delta,
      epsilon, and gamma in TRPV1-positive neurons. Additional biochemical evidence
      supports immunocytochemical results, indicating that AKAP150 preferentially
      associates with certain PKC isoforms in rat trigeminal ganglia neurons. Employing
      siRNA-mediated knock-down of AKAP150 expression, we demonstrate that PKC-mediated
      phosphorylation of TRPV1 and sensitization to a capsaicin response is dependent
      upon functional expression of the AKAP150 scaffolding protein. Furthermore, PKC
      induced sensitization to a thermal stimulus is abrogated in AKAP150 knock-out
      animals relative to wild-type. Collectively, the results from these studies
      indicate that the AKAP150 scaffolding protein functionally modulates PKC-mediated
      phosphorylation and sensitization of the TRPV1 receptor in rat sensory neurons,
      suggesting the scaffolding protein to be an integral regulator of peripheral
      inflammatory hyperalgesia.

PMID- 19767151
TI  - High-grade glioma mouse models and their applicability for preclinical testing.
AB  - High-grade gliomas (WHO grade III anaplastic astrocytoma and grade IV
      glioblastoma multiforme) are the most common primary tumors in the central
      nervous system in adults. Unfortunately, despite great efforts in finding better
      therapies, high-grade glioma remains among the most devastating and deadliest of
      all human cancers. During recent years, genetic and molecular alterations that
      underlie this disease have been identified and advanced our basic knowledge about
      gliomagenesis. Moreover, understanding the molecular biology has also led to the
      development of genetically engineered mouse models that resemble many of the
      features of human gliomas. Ideally, such "patient-like" models should be
      instrumental for preclinical testing of novel therapeutics, but thus far they
      have not yet been widely implemented for this purpose. This review will discuss
      the advantages and shortcomings of the established high-grade glioma mouse models
      with emphasis on their potential applicability for preclinical testing of novel
      drugs and treatment regimens.

PMID- 19767152
TI  - Intervention effects on tobacco use in Arab and non-Arab American adolescents.
AB  - A quasi-experimental design was used to test a modified Project Towards No
      Tobacco (TNT) use program on cigarette smoking in 380 Arab American and 236 non
      Arab American 9th graders in the Midwest. Tenth grade Non-Arab American students
      given the intervention as 9th graders were 23% less likely to experiment (Odds
      Ratio=1.31, 95% CI: 1.05, 1.64) or to have smoked cigarettes in the past 30 days
      (Odd Ratio=1.43 times, 95% CI: 1.03, 2.01) compared to Arab American youth. Arab
      American students reported greater experimentation with water pipe smoking than
      cigarettes (38% vs. 22%), and more current (16% vs. 6%) and regular (7% vs. 3%)
      use of water pipes than cigarettes, respectively. The intervention designed to
      focus on cigarette smoking had non-significant effects on water pipe smoking.
      These findings provide support for a school-based intervention revised to focus
      on prevention as well as cessation and to be culturally consistent. They also
      call for further research and intervention tailoring to address the problem of
      water pipe smoking in a growing Arab American adolescent population.

PMID- 19767153
TI  - The application of platelet-rich plasma may be a novel treatment for central
      nervous system diseases.
AB  - As a potential biological product, platelet-rich plasma (PRP) has been widely
      utilized in the areas of oral and maxillofacial reconstruction, bone and soft
      tissue restoration and wound healing. A recent study reported that the
      application of PRP on interrupted sciatic nerve could promote remyelinization of
      peripheral nerve. This renovated a notion that the application of PRP might
      extend to the nervous system. Most central nervous system (CNS) diseases have a
      series of common pathological changes in the later period of diseases which
      induce neurons and glia apoptosis and aggravate neurological dysfunction. It has
      been demonstrated that the potent restorative function of PRP is mainly based on
      neurotrophic capacity of preparation rich in growth factors (PRGFs) and
      scaffolding effect of platelet-rich gel (PRG), all of which could be certified to
      ameliorate the pathological process of CNS diseases. In view of this, we propose
      a hypothesis that the application of PRP and its derivatives might provide a
      novel therapeutic approach for CNS diseases, especially for traumatic brain or
      spinal cord injury, autoimmune diseases and neurodegenerative disorders such as
      Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis.

PMID- 19767154
TI  - Micropapillary urothelial carcinoma: clinico-pathologic review.
AB  - Micropapillary carcinoma is a rare distinct variant of high grade urothelial
      carcinoma, which has specific morphological characteristics and is almost always
      associated with muscularis propria and vascular invasion. No currently defined
      imaging techniques can reliably diagnose some types of deeply invasive urothelial
      carcinoma of urinary bladder, in particular its micropapillary variant.
      Therefore, the pathological findings are crucial in making the diagnosis.
      Micropapillary carcinoma (MPC) is a tumor with an aggressive clinical course, an
      advanced stage of disease at the time of presentation, and usually a poor
      outcome. Metastatic micropapillary carcinoma to bladder should always be included
      in the differential diagnosis. Correct histological diagnosis of this aggressive
      neoplasm would allow timely, albeit intense, radical treatment of the disease.
      The current most generally favored treatment option for all patients who present
      with MPC is immediate radical cystectomy.

PMID- 19767155
TI  - Risk management and post-marketing surveillance of CNS drugs.
AB  - Drugs affecting the central nervous system span a broad range of chemical
      entities, dosage forms, indications, and risks. Unintended consequences include
      potential abuse and overdose in non-patient drug abusers, deliberate tampering of
      drug dosage forms, and criminal behavior associated with diversion. Regulators
      must consider diverse factors to find the appropriate conditions of approval to
      minimize unintended consequences while enabling a level of access desired by
      health care providers and patients. This commentary appears as part of a special
      issue of Drug and Alcohol Dependence that focuses on risk management and post
      marketing surveillance and addresses key issues that pose real-world challenges
      to pharmaceutical sponsors and regulators in particular. For example, in the
      U.S., Controlled Substances Act drug scheduling can be considered a risk
      management strategy but its legal authorities and administrative processes are
      independent from those of risk management (including Risk Evaluation and
      Mitigation Strategies or REMS); better harmonization of these approaches is vital
      from drug development and regulatory perspectives. Risk management would ideally
      be implemented on a strong science foundation demonstrating that the tools
      employed to mitigate risks and ensure safe use are effective. In reality,
      research and evaluation of tools in this area is in its infancy and will
      necessarily be an evolutionary process; furthermore, there is little precedent
      for linking interventions and program evolution to unintended consequences such
      as regional outbreaks of abuse and diversion. How such issues are resolved has
      the potential to stimulate or stifle innovations in drug development and advance
      or imperil health care.

PMID- 19767156
TI  - Case histories in pharmaceutical risk management.
AB  - The development and implementation of programs in the U.S. to minimize risks and
      assess unintended consequences of new medications has been increasingly required
      by the Food and Drug Administration (FDA) since the mid 1990s. This paper
      provides four case histories of risk management and post-marketing surveillance
      programs utilized recently to address problems associated with possible abuse,
      dependence and diversion. The pharmaceutical sponsors of each of these drugs were
      invited to present their programs and followed a similar template for their
      summaries that are included in this article. The drugs and presenting companies
      were OxyContin, an analgesic marketed by Purdue Pharma L.P., Daytrana and
      Vyvanse, ADHD medications marketed by Shire Pharmaceuticals, Xyrem for narcolepsy
      marketed by Jazz Pharmaceuticals, and Subutex and Suboxone for opioid dependence
      marketed by Reckitt Benckiser Pharmaceuticals Inc. These case histories and
      subsequent discussions provide invaluable real-world examples and illustrate both
      the promise of risk management programs in providing a path to market and/or for
      keeping on the market drugs with serious potential risks. They also illustrate
      the limitations of such programs in actually controlling unintended consequences,
      as well as the challenge of finding the right balance of reducing risks without
      posing undue barriers to patient access. These experiences are highly relevant as
      the FDA increasingly requires pharmaceutical sponsors to develop and implement
      the more formalized and enforceable versions of the risk management term Risk
      Evaluation and Mitigation Strategies (REMS).

PMID- 19767157
TI  - Post-discharge supplementation of vitamins and minerals for preterm neonates.
AB  - Ninety percent of premature babies has nutritional deficiency at discharge. It is
      very important that not only carbohydrates, proteins, fats, but also mineral
      salts, and vitamins are in quantities and adequate quality according to the needs
      of the various scientific neonatal and nutrition programs so as to avoid any
      shortcomings or excess. The growth, neurodevelopmental outcome and quality of
      life depend on, among other factors, an adequate nutritional supply with
      essential nutrients including minerals. It is now recommended that all infants
      and children, including adolescents, have a minimum daily intake of 400 IU of
      vitamin D beginning soon after birth. The standard initial dose of vitamin K1 for
      full term infants (1.0 mg) may be too high for premature infants. The addition of
      folate and especially vitamin B-12 with formula feedings, provided an effective
      and nontoxic means of reducing anemia of prematurity. Several investigators have
      reported higher plasma concentrations of selenium and glutathione peroxidase in
      preterm infants fed with selenium-supplemented formula than in infants fed with
      unsupplemented formula.

PMID- 19767159
TI  - Prescribing policy with dementia drugs: the UK NICE experience.

PMID- 19767158
TI  - Group B streptococcal meningitis: cerebrospinal fluid parameters in the era of
      intrapartum antibiotic prophylaxis.
AB  - OBJECTIVE: Describe cerebrospinal fluid parameters in infants with culture-proven
      Group B streptococcal meningitis in the era of intrapartum antibiotic
      prophylaxis. STUDY DESIGN: Cohort study of the first lumbar puncture from 13,495
      infants cared for at 150 neonatal intensive care units. We compared cerebrospinal
      fluid parameters [white blood cell count, red blood cell count, glucose, and
      protein], demographics, and outcomes between infants with and without Group B
      streptococcal meningitis. RESULTS: We identified 46 infants with Group B
      streptococcal meningitis. The median cerebrospinal fluid white blood cell count
      was 271 cells/mm(3) for infants with Group B streptococcal meningitis and 6
      cells/mm(3) for infants without meningitis (p=0.0001). Of the infants with Group
      B streptococcal meningitis, 9/46 (20%) had negative blood cultures. Meningitis
      complicated 22/145 (15%) of episodes of early-onset Group B streptococcal sepsis
      and 13/23 (57%) of episodes of late-onset Group B streptococcal sepsis.
      CONCLUSIONS: Group B streptococcal meningitis occurs in the presence of negative
      blood cultures. In hospitalized infants who undergo a lumbar puncture, Group B
      streptococcal sepsis is frequently complicated by GBS meningitis.

PMID- 19767160
TI  - GC-MS and GC-IRD studies on dimethoxyamphetamines (DMA): regioisomers related to
      2,5-DMA.
AB  - The mass spectrum of the drug of abuse 2,5-dimethoxyamphetamine (2,5-DMA) is
      characterized by an imine fragment base peak at m/z 44 and additional fragments
      at m/z 151/152 for the dimethoxybenzyl cation and radical cation, respectively.
      Five positional ring isomers of dimethoxyamphetamines (DMA) have an isomeric
      relationship to 2,5-DMA. All six compounds have the same molecular weight and
      produce similar EI mass spectra. This lack of mass spectral specificity for the
      isomers in addition to the possibility of chromatographic coelution could result
      in misidentification. The lack of reference materials for the potential imposter
      molecules constitutes a significant analytical challenge. Perfluoroacylation of
      the amine group reduced the nitrogen basicity and provided individual
      fragmentation pathways for discrimination between these compounds based on some
      unique fragment ions and the relative abundance of common ions. GC-IRD studies
      provided additional structure-IR spectra relationships and yielded confirmation
      level identification for each of the six regioisomeric dimethoxyamphetamines. The
      amines and their perfluoroacylated derivatives were resolved by capillary gas
      chromatography and the amines showed excellent resolution on the more polar
      stationary phase, Rtx-200.

PMID- 19767161
TI  - Partial bowel obstruction in a 2-month-old child. A delayed diagnosis of anal
      abuse.
AB  - We present the case of an anal sexual abuse involving a 2-month-old boy, who was
      admitted to the Pediatric Surgery Unit of the University of Padua for low bowel
      obstruction. The infant had been already hospitalized for 3 days in a peripheral
      hospital and treated with daily rectal wash-outs for a fecaloma. Only after a
      careful interpretation of the plain abdominal radiograph, along with the
      performance of a rectoscopy and a laparotomy, a vegetable foreign body (about 3
      cm in diameter and 7 cm in length) was discovered in the sigma. The morphology
      and dimensions of the foreign body, as well as its location, left no doubt about
      the etiology of the partial bowel obstruction, proving that it was clearly
      related to an anal sexual abuse.

PMID- 19767162
TI  - Early infantile epileptic encephalopathy with unusual favourable outcome.
AB  - The authors report the case of an infant suffered from early infantile epileptic
      encephalopathy with suppression-burst, or Ohtahara syndrome, a severe form of
      epilepsy in early childhood. The patient was treated with vigabatrin causing a
      favourable response. This unusual outcome may be related with the normality of
      neuroimaging and metabolic studies, as happens with idiopathic West syndrome
      cases.

PMID- 19767163
TI  - [Endoscopic mucosal resection of a polypoid sessile adenoma over a lipoma].

PMID- 19767164
TI  - Assessment of the corticospinal tract alterations before and after resection of
      brainstem lesions using Diffusion Tensor Imaging (DTI) and tractography at 3T.
AB  - The purpose of the study was to investigate the role of Diffusion Tensor Imaging
      (DTI) and Diffusion Tensor Tractography (DTT) on the corticospinal tract
      alterations due to space occupying lesions in the brainstem before and after
      surgical resection. Pre- and post-surgical DTI data were acquired in 14 patients
      undergoing surgical resection of brainstem lesions. Patterns of corticospinal
      tract (CST) alteration on DTT were compared with the neurological exams of the
      patients pre- and post-operatively. DTT, especially in 3D movie format, seemed
      very helpful for evaluating the relationship of the lesions with the
      corticospinal tracts for surgical approach. None of the patients developed
      additional motor deficit related to surgery except one patient who presented with
      cerebellar ataxia after surgery. All of the patients with normal CST on DTT
      presented without motor deficit on neurological exam. The sensitivity,
      specificity, positive predictive and negative predictive values of DTT before
      surgery were 100%, 63.6%, 42.9% and 100%, and the corresponding values after
      surgery were 100%, 96%, 75% and 100% respectively. Although it has low
      specificity before surgery, DTT is a potentially useful technique in evaluating
      the effects of brainstem lesions and surgical resection on the relevant
      corticospinal tracts with high negative predictive value and higher specificity
      after surgery.

PMID- 19767165
TI  - Contrast-enhanced MRI of subchondral cysts in patients with or at risk for knee
      osteoarthritis: the MOST study.
AB  - OBJECTIVE: The aim of the study was (1) to evaluate contrast enhancement patterns
      of subchondral cysts on magnetic resonance imaging and (2) to discuss possible
      radiological explanations of cyst enhancement based on existing theories of
      subchondral cyst formation in osteoarthritis. MATERIALS AND METHODS: The
      Multicenter Osteoarthritis Study (MOST) is a NIH-funded longitudinal
      observational study for individuals who have or are at high risk for knee
      osteoarthritis. All subjects with available non-enhanced and contrast-enhanced
      MRI were included. The tibiofemoral and patellofemoral joints were divided in 14
      subregions. The presence and size of subchondral cysts and bone marrow edema-like
      lesions (BMLs) were scored semiquantitatively in each subregion on non-contrast
      enhanced MRI from 0 to 3. Enhancement of subchondral cysts was evaluated on
      contrast-enhanced MRI as grade 0 (absent), grade 1 (partial enhancement), or
      grade 2 (full enhancement). The adjacent articular cartilage was scored in each
      subregion on non-enhanced MRI as grade 0 (intact), grade 1 (partial thickness
      loss), or grade 2 (full thickness loss). RESULTS: Four hundred knees were
      included (1 knee per person, 5600 subregions). Subchondral cysts were detected in
      260 subregions (4.6%). After intravenous contrast administration, 245 cysts
      (94.2%) showed full enhancement, 12 (4.6%) showed partial enhancement and 3
      (1.2%) showed no enhancement. Enhancing BMLs were found in 237 (91.2%) subregions
      containing cysts, which were located adjacent or in the middle of BMLs. In 121
      subregions (46.5%) having cysts, no adjacent full thickness cartilage loss was
      detected. CONCLUSION: Most subchondral cysts demonstrated full or partial
      contrast enhancement, and were located adjacent or in the midst of enhancing
      BMLs. As pure cystic lesions are not expected to enhance on MRI, the term
      "subchondral cyst-like bone marrow lesion" might be appropriate to describe these
      lesions.

PMID- 19767166
TI  - Qualitative and quantitative analysis of steroidal saponins in crude extracts
      from Paris polyphylla var. yunnanensis and P. polyphylla var. chinensis by high
      performance liquid chromatography coupled with mass spectrometry.
AB  - High performance liquid chromatography coupled with electrospray ionization multi
      stage tandem mass spectrometry (HPLC-ESI-MS(n)) and triple quadrupole mass
      spectrometric detection (HPLC-ESI-MS/MS), respectively, had been employed for the
      simultaneous identification and quantification of steroidal saponins in the
      rhizomes of Parispolyphylla var. yunnanensis and P. polyphylla var. chinensis,
      which are the qualified plants of "Chonglou" in Chinese. The HPLC experiments
      were performed by means of a reversed-phase C-18 column and a binary mobile phase
      system consisting of 0.1% aqueous formic acid and acetonitrile under gradient
      elution conditions. The characteristic fragmentation patterns of diosgenin- and
      pennogenin-type steroidal saponins were investigated using ESI-MS(n) in negative
      ion mode. The MS(n) data of the [M-H](-) ions provided structural information on
      the sugar sequence of the oligosaccharide chains and the aglycones of steroidal
      saponins. As a result, ten and seven saponins were determined in P. polyphylla
      var. yunnanensis and P. polyphylla var. chinensis, respectively, including four
      unknown compounds. One unknown compound was tentatively identified as diosgenin-3
      O-alpha-L-rhamnopyranosyl(1-->4) [alpha-L-rhamnopyranosyl(1-->2)]-beta-D
      glucopyranoside and the aglycones of the other three new compounds were reported
      from Chonglou for the first time. The developed HPLC-ESI-MS/MS method was
      validated and found to be satisfactorily linear, selective and robust. The limits
      of detection (LODs) and quantitation (LOQs) ranged, respectively, from 0.5 to 10
      ng/mL and 2 to 34 ng/mL depending on six various compounds. The intra- and inter
      day precisions of the method were evaluated and were less than 5.0%. Recoveries
      ranged from 92% to 104% for all compounds. The established quality evaluation
      method was successfully used for simultaneous quantification of six predominant
      steroidal saponins in the rhizomes of these two Paris species.

PMID- 19767167
TI  - Facing uncertainty as a medical student--a qualitative study of their reflective
      learning diaries and writings on specific themes during the first clinical year.
AB  - OBJECTIVE: Tolerance of uncertainty related to the complex work is a major
      dimension of general practitioner's (GP) profession. Strategies for managing
      uncertainty have been studied among GPs but less is known about how medical
      students develop tolerance of uncertainty during their studies. The aim of this
      study was to investigate how the medical students experience uncertainty during
      their first clinical years and how their feelings develop with time as they
      progress from the 3rd year to the 4th year. METHODS: The material consisted of 22
      students' reflective learning diaries and writings on specific themes collected
      during the 3rd and 4th year of their medical studies. The analysis was performed
      using thematic content analysis. In this article we present the results related
      to the theme of uncertainty. RESULTS: Uncertainty is a major cause of mental
      strain for medical students, particularly fear of making mistakes. Main themes
      related to facing uncertainty and found in the diaries and writings were
      insecurity of professional skills, own credibility, facing with the inexactness
      of medicine, fear of making mistakes, coping with responsibility, and tolerating
      oneself as incomplete and accepting oneself as a good-enough doctor-to-be. Common
      steps of development towards tolerance of uncertainty were found in diaries over
      a one-year time period as the students progressed in their clinical studies.
      CONCLUSIONS: Reflective writing showed to be an effective means for the students
      of both expressing and dealing with uncertainty, both with the difficult and the
      pleasant feelings and the experiences the students had with their first patient
      contacts. It also gave some of them the means of self-reflection which they
      afterwards found worthwhile. PRACTICE IMPLICATIONS: Reflective writing is
      powerful tool which medical students could use to facilitate their maturation
      process what comes to uncertainty during their first clinical year.

PMID- 19767168
TI  - Multiple health behavior clusters among female college students.
AB  - OBJECTIVE: To examine prevalence of multiple unhealthful behaviors and detect
      clusters of unhealthful behaviors among college women. METHODS: Women ages 18-22
      enrolled full-time at an urban university located in the Northeastern United
      States were invited to complete an online survey, which assessed maintenance
      behaviors: fruits/vegetables, physical activity, cervical screening and at-risk
      behaviors: frequent drinking, smoking, and non-use of protective measures during
      sexual intercourse. Of 4774 invited, complete data is available for 1463
      participants (1463/4774=30.6%). RESULTS: Nearly 65% had two or more unhealthful
      behaviors. Three distinct clusters were defined: cluster one included women who
      were lower in health maintenance and higher in at-risk behaviors; cluster two
      included women who were lower in health maintenance and lower in at-risk
      behaviors; and cluster three included women who were higher in health maintenance
      and intermediate in at-risk behaviors. CONCLUSION: These clustering patterns
      suggest health programs directed at college students address multiple behaviors
      simultaneously. PRACTICE IMPLICATIONS: Programs targeting multiple behaviors
      should consider activities for those seen within and outside of the context of
      health services.

PMID- 19767169
TI  - [Antimicrobial prophylaxis for caesarean delivery: before or after cord clamping?
      A meta-analysis].
AB  - OBJECTIVE: The objective of this systematic review was to assess the effect of
      preoperative rather than after umbilical cord clamping antimicrobial prophylaxis
      for caesarean delivery on maternal and neonatal infectious postoperative
      morbidity. STUDY DESIGN: Meta-analysis. METHODS: Three electronic databases
      (Pubmed, Cochrane Central Register of Randomized Controlled Trials and Embase)
      were searched without language restriction and retrieved 201 potentially relevant
      trials. Five randomized controlled trials (n=1108) studying the timing of
      antimicrobial prophylaxis for caesarean section were included. The quality of
      included trials was assessed on the modified Oxford validity scale. RESULTS:
      Preoperative administration of antibiotics (n=456) rather than after cord
      clamping (n=563) provides a significant reduction in the incidence of
      endometritis (Odds Ratio (OR) 0.59 [95% Confidence Interval (CI) 0.35-0.98]) and
      of total maternal infectious morbidity (OR 0.51 [95% CI 0.32-0.82]). This benefit
      was not observed regarding the incidence of wound infection (Peto OR 0.58 [95% CI
      0.29-1.16]), neonatal infection (Peto OR 1.06 [95% CI 0.57-1.96]), neonatal
      sepsis workup (OR 1.02 [95% CI 0.67-1.54]), neonatal documented sepsis (Peto OR
      0.93 [95% CI 0.43-2.02]) or neonatal intensive care unit admission (OR 0.97 [95%
      CI 0.61-1.56]). No significant heterogeneity was observed between the included
      studies. CONCLUSION: This meta-analysis provides strong evidence that the
      preoperative rather than after cord clamping administration of antimicrobial
      prophylaxis for caesarean delivery provides a reduction in the incidence of
      endometritis and maternal total infectious morbidity without affecting the
      incidence of wound infection and neonatal infectious morbidity.

PMID- 19767170
TI  - [Three cases of IgM monoclonal gammopathy with haemostasis dysfunction].
AB  - We relate three cases of IgM gammopathy with haemostatic dysfunction in the
      perioperative period. The acquired von Willebrand syndrome due to IgM gammopathy
      is rare and sometimes serious. Its different treatments and their efficiency are
      discussed: desmopressin, intravenous gammaglobulin, chemotherapy and
      plasmapheresis.

PMID- 19767171
TI  - [New oral anticoagulant agents: do not walk out of the line].

PMID- 19767172
TI  - [Experiment of an anesthetic adverse events reporting].
AB  - OBJECTIVES: This article summarizes functioning and results of anaesthesia
      adverse effects reporting system over its first 18 months, from August 2006 to
      February 2008. STUDY DESIGN: Monocentric retrospective study. METHODS: Reporting
      system is available 24/24h, 7/7 to every employee with an individual password. A
      committee with anaesthesiologists, nurses and risk management engineer examines
      every notification by two months. We evaluated number of reports, type of
      reporter, type of dysfunction reported and solutions. Numerical data are compared
      with a Student t test or X(2) test. A p-value of less than 0.05g being considered
      as statistically significant. RESULTS: One hundred and eighty-five reports were
      registered for the first 18 months (1% of anesthesia activity) with a slowdown
      with time (p=0.02). Eighty-six percent of the statements were made by
      anesthesiologists, but some physicians had never reported. Malfunctions shared
      between different services (identity, operating room organisation) are rarely
      solved (67%) compared to specific anesthesia problems (93%) (p<0.001).
      CONCLUSION: The reporting system is simple and available but some professionals
      don't declare, generating reporting bias. This network underlines major general
      dysfunctions (identity) but ways to solve are limited to date.

PMID- 19767173
TI  - [Effects of the Internet on the dissemination of medical information: some
      thoughts on applied ethics].
AB  - Learned and professional societies as well as health authorities must attempt to
      provide free access to their databases for physicians, by a simple repertory of
      key words and, if necessary, by portals. Although information available for
      physicians may not be intended to be secret, it often requires some professional
      training to be interpreted appropriately. The principles of the Code of Medical
      Ethics, as transcribed in the Public Health Code, apply to all forms and media of
      information and communication. In public spaces, readers must be guaranteed that
      information written by physicians corresponds to the state of the art, that it is
      not advertising or self-promotion or commercial, that it was developed by a
      process ensuring quality, and that it distinguishes clearly between a popularized
      description of scientific data and what remains uncertain because research is on
      going. The public should be informed about the source of the information they
      see, the editorial quality of the site, and any potential financial dependence or
      conflicts of interest. According to the medical association, prudence is
      recommended for physicians who moderate chat-rooms and discussion lists. List
      moderation, like any other type of medical activity, must not be improvised; it
      requires prudence, thought, and training.

PMID- 19767174
TI  - A preliminary examination of the relationships between posttraumatic stress
      symptoms and crack/cocaine, heroin, and alcohol dependence.
AB  - High rates of co-occurrence between posttraumatic stress (PTS) and substance use
      disorders (SUDs) have led to the suggestion that substance use among individuals
      experiencing PTS symptoms might serve a self-medication function. However,
      research is still needed to provide a more comprehensive evaluation of the unique
      associations between PTS symptom clusters and substances (licit and illicit) with
      both anxiolytic/depressant and stimulant properties. Consequently, this study
      examined the relationship between severity of different PTS symptom clusters and
      heroin, crack/cocaine, and alcohol dependence among 48 treatment-seeking SUD
      patients with a history of traumatic exposure. No evidence was found for a
      relationship between PTS symptom clusters and crack/cocaine or alcohol
      dependence; however, results suggested a relationship between hyperarousal and
      avoidance (inversely related) symptoms and heroin dependence. Results are
      discussed in terms of their implications for understanding motivations underlying
      the substance of choice among individuals with PTS symptoms, as well as the
      development of treatments for co-occurring PTS and SUDs.

PMID- 19767175
TI  - Extensive nonbacterial thrombotic endocarditis isolated to the tricuspid valve in
      primary antiphospholipid syndrome.
AB  - Nonbacterial thrombotic endocarditis is a condition characterized by
      noninfectious valvular vegetations and is associated with numerous conditions,
      including the antiphospholipid syndrome. Although vegetations most frequently
      affect the left-sided valves, isolated involvement of the right-sided valves
      rarely occurs. Ideal management of the lesions, from both medical and surgical
      perspectives, is not well defined. The authors report the case of a patient who
      presented with clinically symptomatic isolated tricuspid valve and right atrial
      nonbacterial thrombotic endocarditis due to primary antiphospholipid syndrome,
      who was subsequently managed with diuretics and anticoagulation and has remained
      clinically stable.

PMID- 19767176
TI  - Pyrrolidine dithiocarbamate protects the piriform cortex in the pilocarpine
      status epilepticus model.
AB  - Pyrrolidine dithiocarbamate (PDTC) has a dual mechanism of action as an
      antioxidant and an inhibitor of the transcription factor kappa-beta. Both,
      production of reactive oxygen species as well as activation of NF-kappaB have
      been implicated in severe neuronal damage in different sub-regions of the
      hippocampus as well as in the surrounding cortices. The effect of PDTC on status
      epilepticus-associated cell loss in the hippocampus and piriform cortex was
      evaluated in the rat fractionated pilocarpine model. Treatment with 150 mg/kg
      PDTC before and following status epilepticus significantly increased the
      mortality rate to 100%. Administration of 50 mg/kg PDTC (low-dose) did not exert
      major effects on the development of a status epilepticus or the mortality rate.
      In vehicle-treated rats, status epilepticus caused pronounced neuronal damage in
      the piriform cortex comprising both pyramidal cells and interneurons. Low-dose
      PDTC treatment almost completely protected from lesions in the piriform cortex. A
      significant decrease in neuronal density of the hippocampal hilar formation was
      identified in vehicle- and PDTC-treated rats following status epilepticus. In
      conclusion, the NF-kappaB inhibitor and antioxidant PDTC protected the piriform
      cortex, whereas it did not affect hilar neuronal loss. These data might indicate
      that the generation of reactive oxygen species and activation of NF-kappaB plays
      a more central role in seizure-associated neuronal damage in the temporal cortex
      as compared to the hippocampal hilus. However, future investigations are
      necessary to exactly analyze the biochemical mechanisms by which PDTC exerted its
      beneficial effects in the piriform cortex.

PMID- 19767177
TI  - Family context and duration of untreated psychosis (DUP): results from the Sao
      Paulo Study.
AB  - BACKGROUND: Duration of untreated psychosis (DUP) depends on several factors,
      including socio-demographic, socioeconomic, clinical and contextual
      circumstances, such as availability of mental health services. Living
      arrangements may also play a role, especially in low- and middle-income
      countries, where most people who develop psychosis live with their relatives.
      METHODS: Population-based study of first-episode psychosis in Sao Paulo, Brazil.
      Participants were aged 18-64 years, lived in a defined geographic area of the
      city and had a first contact in life with mental health services due to a
      psychotic episode. Duration of untreated psychosis was defined as the period
      between onset of first psychotic symptom and first contact with health service
      due to psychosis. The median DUP was used to classify participants into short and
      long DUP. Psychopathology, social adjustment and psychiatric diagnoses were made
      with standardized assessments. Type of service sought and living arrangements
      were examined. RESULTS: Two hundred participants were included (52% women, 61%
      non-affective psychoses). The median DUP was 4.1 weeks (inter-quartile range: 1.9
      11.4), and was shorter for affective psychoses. Most participants had their first
      contact with psychiatric emergency services. Those who did not live with a
      relative (children older than 18 years, parents, partner) were more likely to
      present long DUP (OR: 2.63; 95%CI: 0.98-7.04); p=0.05). CONCLUSION: The DUP in
      Sao Paulo was shorter than expected. Living arrangements may play an important
      role in shortening the DUP in urban centres of low- and middle income countries
      that have a network of mental health services.

PMID- 19767178
TI  - Depth of the olfactory sulcus: a marker of early embryonic disruption in
      schizophrenia?
AB  - Embryonic insults during early gestation increase the risk of schizophrenia.
      Abnormal forebrain development during this period is often characterized by a
      shallow olfactory sulcus. The adjacent orbital sulcus does not develop until the
      third trimester and so is immune to early intrauterine insults. We measured
      olfactory and orbital sulcal depths in 36 patients and 28 control subjects.
      Patients had shallower olfactory sulci, but normal orbital sulci. Olfactory and
      orbital sulcal depths were correlated in controls, but not in patients. Olfactory
      sulcal depth may therefore be a biomarker denoting an early embryonic disruption
      in individuals at risk for schizophrenia.

PMID- 19767179
TI  - Anatomical brain connectivity and positive symptoms of schizophrenia: a diffusion
      tensor imaging study.
AB  - Structural brain changes in schizophrenia are well documented in the neuroimaging
      literature. The classical morphometric analyses of magnetic resonance imaging
      (MRI) data have recently been supplemented by diffusion tensor imaging (DTI),
      which mainly assesses changes in white matter (WM). DTI increasingly provides
      evidence for abnormal anatomical connectivity in schizophrenia, most often using
      fractional anisotropy (FA) as an indicator of the integrity of WM tracts. To
      better understand the clinical significance of such anatomical changes, we
      studied FA values in a whole-brain analysis comparing paranoid schizophrenic
      patients with a history of auditory hallucinations and matched healthy controls.
      The relationship of WM changes to psychopathology was assessed by correlating FA
      values with PANSS scores (positive symptoms and severity of auditory
      hallucinations) and with illness duration. Schizophrenic patients showed FA
      reductions indicating WM integrity disturbance in the prefrontal regions,
      external capsule, pyramidal tract, occipitofrontal fasciculus, superior and
      inferior longitudinal fasciculi, and corpus callosum. The arcuate fasciculus was
      the only tract which showed increased FA values in patients. Increased FA values
      in this region correlated with increased severity of auditory hallucinations and
      length of illness. Our results suggest that local changes in anatomical integrity
      of WM tracts in schizophrenia may be related to patients' clinical presentation.

PMID- 19767180
TI  - Osteoconductive conjugation of bone morphogenetic protein-2 onto
      titanium/titanium oxide surfaces coated with non-biofouling poly(poly(ethylene
      glycol) methacrylate).
AB  - This paper describes a method for introducing osteoconductivity onto titanium, a
      widely used material for implants, as well as maintaining its non-biofouling
      ("bioinert") property, in the aim of increasing bioactivity of titanium for its
      wider applications to biomedical areas. Titanium substrates were coated with a
      non-biofouling poly(poly(ethylene glycol) methacrylate) (pPEGMA) by surface
      initiated polymerization, and bone morphogenetic protein-2 (BMP-2) was chemically
      conjugated to the activated pPEGMA films. The non-biofouling property and
      increased bioactivity of titanium were confirmed by the maintenance of the
      cellular response of mesenchymal stem cells on the titanium substrates: the BMP-2
      conjugated pPEGMA films induced the adhesion and differentiation of mesenchymal
      stem cells, while non-conjugated pPEGMA films showed the excellent resistance
      against the adhesion of the cells.

PMID- 19767181
TI  - Gastric healing effect of melatonin against different gastroinvasive agents in
      cholestatic rats.
AB  - BACKGROUND AND OBJECTIVE: The frequency of gastrointestinal ulceration is higher
      in jaundiced patients than in healthy population. The aim of this study was to
      assess the effect of pretreatment with melatonin, a potent scavenger of reactive
      oxygen species, on stress-induced gastric ulcers of cholestatic rats. MATERIALS
      AND METHODS: Cholestasis was induced by surgical ligation of bile-duct and sham
      operated rats served as sham animals. The animals received saline or melatonin
      (1, 3 or 10mg/kg) before stress induction. Three different types of
      gastroinvasive agents including ethanol, indomethacin or water immersion were
      used as stress agents to induce gastric ulceration. RESULTS: Gastric mucosal
      damage induced by different gastroinvasive agents was significantly greater in
      bile-duct-ligated rats than in sham ones. Melatonin was protective against
      ethanol-, indomethacin- and water immersion-induced gastric damage in bile-duct
      ligated and sham rats, dose-dependently, but the protective effect of melatonin
      was greater in cholestatic rats than sham rats in all three different series of
      experiments. CONCLUSIONS: In conclusion, pretreatment of rats with melatonin
      protected gastric mucosa of cholestatic rats more effectively than the sham ones
      possibly by a mechanism involving the scavenging of free radicals.

PMID- 19767182
TI  - [Palivizumab immunoprophylaxis: use in clinical practice, safety and beneficial
      effects in France].
AB  - BACKGROUND: Infants treated have been followed for one year in order to assess
      conditions of use of palivizumab, safety, tolerability, and its impact on
      respiratory syncytial virus (RSV) hospitalisation rate. PATIENTS AND METHODS:
      Patients who received palivizumab during the epidemic season 2005-2006 were
      eligible. Follow-up was carried out 12 months after initiation of prophylaxis.
      RESULTS: Sixty-four neonatal level II and III centers, pulmonary and cardiology
      units enrolled 1420 children. Mean follow-up was 10.9+/-0.2 months, mean
      gestational age (GA) 30+/-4 weeks and mean age at the start of prophylaxis was 5
      months. Median number of injections was 5 and mean time interval between 2
      consecutive injections was 30+/-6 days. Treatment was prescribed in accordance
      with the marketing authorisation indications (MA) for 84% of patients. For
      preterm infants born before 35 SA and less than 6 months of age, 60% was born
      before 33 SA and without BDP. The global readmission rate (for more than 24h) for
      documented RSV infection during the period of protection by palivizumab was 2.7%
      (37 in 1371) for all treated children: respectively 2% [IC(95%)=1.3-3.2], 2.7%
      [IC(95%)=0.7-4.7] and 3.7% [IC(95%)=0.8-6.6] for preterm infants less than 6
      months of age, preterm from 6 to 24 months of age and for children with
      congenital cardiopathy. Palivizumab safety and tolerability were good.
      CONCLUSION: Evaluation of palivizumab prophylaxis in clinical practice confirms
      the clinical characteristics of treated infants, outlines their evolution and
      confirms safety of treatment. MA were generally well observed and a registry
      could be usefull to track the impact of the treatment out of MA.

PMID- 19767183
TI  - Morphogenesis of Kiitricha marina Nozawa, 1941 (Ciliophora, Spirotrichea), a
      possible model for the ancestor of hypotrichs s. l.
AB  - Recent studies suggested that the marine ciliate Kiitricha Nozawa, 1941
      represents a basal branch in the spirotrichs. The present study reflects the
      morphogenetical investigation of Kiitricha marina Nozawa, 1941. The results
      listed below show an extremely unusual developmental pattern compared with all
      other known forms in the class Spirotrichea or hypotrichs s. l. (i) The
      differentiation of the ciliary structures from the primordia occurs after cell
      division. This makes Kiitricha marina Nozawa, 1941 unique among hypotrichs s. l.
      (ii) Since the anlage of the undulating membranes in the opisthe derives from the
      division of the dedifferentiated parental structure and thus is not formed
      independently, Kiitricha marina Nozawa, 1941 is also unique among spirotrichs.
      (iii) Most somatic cirral structures appear in a post-anlage pattern, i.e. all
      cirri exhibit a primary arrangement in the sense that they are distributed as
      though they had just been segregated from the anlagen. (iv) Unlike most other
      known hypotrichs s. l., the undulating membrane-anlage does not contribute a
      frontal cirrus. (v) The dorsal kineties are formed in two ways: (a) from the
      posterior portion of the cirral anlagen which later generate the new dorsal
      kinety segments; and (b) by the irregular proliferation of dikinetids in the long
      dorsal kineties. (vi) All cirral anlagen are formed intrakinetally from the
      dedifferentiated parental cirri and develop in a primary mode. Taken
      collectively, these findings suggest that Kiitricha is a basal branching
      hypotrich and therefore a possible model for the ancestor of the hypotrichs s. l.

PMID- 19767184
TI  - Re-classification of Pheopolykrikos hartmannii as Polykrikos (Dinophyceae) based
      partly on the ultrastructure of complex extrusomes.
AB  - Athecate, pseudocolony-forming dinoflagellates have been classified within two
      genera of polykrikoids, Polykrikos and Pheopolykrikos, and different views about
      the boundaries and composition of these genera have been expressed in the
      literature. The photosynthetic polykrikoid Pheopolykrikos hartmannii, for
      instance, was originally described within Polykrikos and is now known to branch
      closely with several Polykrikos species in molecular phylogenetic analyses of
      ribosomal gene sequences. In this study, we report the first ultrastructural data
      for this species and demonstrate that Ph. hartmannii has all of the features that
      characterize the genus Polykrikos, including the synapomorphic "taeniocyst
      nematocyst complex". We also demonstrate that the ultrastructure of the
      chloroplasts in Ph. hartmannii conforms to the usual peridinin-containing
      chloroplasts of most photosynthetic dinoflagellates, which improves inferences
      about the origin(s) and evolution of photosynthesis within the genus. After
      taking into account all of the ultrastructural data on polykrikoids presented
      here and in the literature, this species is re-classified to its original status
      as Polykrikos hartmannii.

PMID- 19767185
TI  - Unikaryon phyllotretae sp. n. (Protista, Microspora), a new microsporidian
      pathogen of Phyllotreta undulata (Coleoptera; Chrysomelidae).
AB  - The microsporidium Unikaryon phyllotretae sp. n., a new pathogen of Phyllotreta
      undulata, is described based on light microscopic and ultrastructural
      characteristics. Microscopic examination of parasitized individuals revealed two
      types of spores. The majority of the spores were of the first type, which are
      oval and measured 2.74+/-0.17 x 1.93+/-0.17 microm when fresh. Fresh spores of
      the second type (very rare) are elongated and measured 4.39+/-0.18 x 1.61+/-0.20
      microm. All life stages have single nuclei. Sporogony ends with uninucleate
      single sporoblasts and spores. The spores were only observed in Malpighian
      tubules. The isofilar polar filament of the parasite has six to eight coils, and
      a well-developed polaroplast was of the lamellated type, with closely packed
      anterior lamellae and loosely packed posterior lamellae.

PMID- 19767186
TI  - Ocular prostaglandin production and morphology in mice lacking a single isoform
      of cyclooxygenase.
AB  - Prostaglandins have many important roles in ocular physiology and are used
      clinically for the treatment of glaucoma. The aim of this study was to analyse
      the contribution of each cyclooxygenase isoform to ocular prostaglandin
      production using isoform-specific knockout mice. Ex vivo PGE(2), 6-keto
      PGF(1alpha), and TXB(2) production was measured from whole eyes, corneal tissue,
      uveoscleral tissue, lens, retina and optic nerve using enzyme-linked
      immunosorbant assays. Ocular immunohistochemical and histological analysis was
      also conducted for each genotype. Levels of each of the prostaglandins measured
      were significantly decreased in the corneal tissue, uveoscleral tissue, lens,
      retina and optic nerve of COX-1(-/-) mice in comparison with wild-type mice. In
      contrast, COX-2(-/-) mice had similar levels of ocular prostaglandin production
      to wild-type mice. These results suggest that COX-1 is the principal isoform
      responsible for prostaglandin production in the mouse eye. The absence of COX-1
      or COX-2 did not appear to effect ocular development in these mice.

PMID- 19767188
TI  - Protein phosphatases take the mitotic stage.
AB  - Following the identification of cyclin-dependent kinases in the 1980s, kinases
      were hailed as the directors of mitosis. Although the action of kinases must
      necessarily be reversible, only recently has the involvement of specific
      phosphatases in mitosis become appreciated. Studies are now revealing how the
      timely execution of mitotic events depends on the delicate interplay between
      kinases and phosphatases. To date, the best-characterized mitotic phosphatases
      are Cdc25, that is required for entry into mitosis and Cdc14, that controls exit
      from mitosis in budding yeast. Recent work has now exposed the conserved serine
      threonine phosphatases PP1 and PP2A as key regulators of various mitotic
      processes.

PMID- 19767189
TI  - TOR signaling in invertebrates.
AB  - The Target of Rapamycin (TOR), a protein kinase, is the central node of a highly
      conserved signaling network that regulates cell growth in response to nutrients,
      hormones, and stresses. TOR is found in two functionally distinct complexes,
      TORC1 and TORC2. In this review we address the most recent advances in TOR
      signaling in invertebrate model organisms, including yeasts, plants, worms, and
      insects.

PMID- 19767190
TI  - Eukaryotic DNA replication control: lock and load, then fire.
AB  - The initiation of chromosomal DNA replication involves initiator proteins that
      recruit and load hexameric DNA helicases at replication origins. This helicase
      loading step is tightly regulated in bacteria and eukaryotes. In contrast to the
      situation in bacteria, the eukaryotic helicase is loaded in an inactive form.
      This extra 'lock and load' mechanism in eukaryotes allows regulation of a second
      step, helicase activation. The temporal separation of helicase loading and
      activation is crucial for the coordination of DNA replication with cell growth
      and extracellular signals, the prevention of re-replication and the control of
      origin activity in response to replication stress. Initiator proteins in bacteria
      and eukaryotes are structurally homologous; yet the replicative helicases they
      load are unrelated. Understanding how these helicases are loaded and how they act
      during unwinding may have important implications for understanding how DNA
      replication is regulated in different domains of life.

PMID- 19767191
TI  - Developing a monitoring method facilitating continual improvements in the sorting
      of waste at recycling centres.
AB  - Beneficial use of waste relies on efficient systems for collection and
      separation. In Sweden, a bring system involving recycling centres for collection
      of bulky, electr(on)ic and hazardous waste has been introduced. A significant
      share of this waste is incorrectly sorted, causing downstream environmental
      implications. At present, however, there is a lack of affordable and accurate
      monitoring methods for providing the recycling centres with the necessary facts
      for improving the sorting of waste. The aim of this study was therefore to
      evaluate the usability of a simplified and potentially more suitable waste
      monitoring method for recycling centres. This method is based on standardised
      observations where the occurrence of incorrect sorting is monitored by taking
      digital pictures of the waste which then are analysed according to certain
      guidelines. The results show that the developed monitoring method could offer a
      resource-efficient and useful tool for proactive quality work at recycling
      centres, involving continuous efforts in developing and evaluating measures for
      improved sorting of waste. More research is however needed in order to determine
      to what extent the obtained results from the monitoring method are reliable.

PMID- 19767192
TI  - A label-free amperometric immunosensor based on biocompatible conductive redox
      chitosan-ferrocene/gold nanoparticles matrix.
AB  - A novel experimental methodology based on the unique characteristics of chitosan
      branched ferrocene (CS-Fc) and gold nanoparticles (Au NPs) was developed to
      design a label-free amperometric immunosensor for the sensitive detection of
      hepatitis B surface antigen (HBsAg) as a model protein. The controllable
      electrodeposition of CS-Fc solution formed a three-dimensional robust film with
      good biocompatibility and large surface area for the assembly of Au NPs and
      further immobilization of hepatitis B surface antibody (HBsAb) on an electrode.
      The morphologies and electrochemistry of the formed nanocomposite biofilm were
      investigated by using scanning electron microscopy and electrochemical techniques
      including cyclic voltammetry and electrochemical impedance spectroscopy,
      respectively. The HBsAg concentration was measured through the decrease of
      amperometric responses in the corresponding specific binding of antigen and
      antibody. The decreased differential pulse voltametric values were proportional
      to the HBsAg concentration in the range of 0.05-305ngmL(-1) with a detection
      limit 0.016ng. This would provide an approach for the application of mediator in
      immunoassays.

PMID- 19767193
TI  - Fe-substituted titanate nanosheets intercalated with hemoglobin for direct
      electrochemistry.
AB  - Fe-substituted titania nanosheets (FTNS) are used as support matrixes for
      hemoglobin (Hb) immobilization and protein electrode fabrication to study the
      direct electron transfer between the redox centers of proteins and the electrode.
      X-ray diffraction (XRD) and high-resolution transmission electron microscope
      (HRTEM) reveal that the Hb-FTNS composite has an ordered layered structure with a
      monolayer arrangement in the interlayers. The native structure of the
      intercalated Hb is maintained, as indicated by the ultraviolet-visible (UV-vis)
      and Fourier-transform infrared (FTIR) spectroscopy. The Hb-FTNS modified
      electrode shows a fast direct electron transfer for the Hb Fe(III)/Fe(II) redox
      couple and exhibits good electrocatalytic properties for the reduction of
      H(2)O(2). The sensitivity of Hb-FTNS modified electrode for the reduction of
      H(2)O(2) is 156mAM(-1)cm(-2) in the linear range of 2-65 microM, which is 18
      times higher than that of Hb-titania nanosheets modified electrode (8.54mAM(
      1)cm(-2)), suggesting that the Fe doping maybe an efficient method to improve the
      electrochemical performance of TNS for biosensors, biofuel cells and
      bioelectronics applications.

PMID- 19767194
TI  - Direct electrochemistry of glucose oxidase and biosensing for glucose based on
      carbon nanotubes@SnO(2)-Au composite.
AB  - Multiwalled carbon nanotubes@SnO(2)-Au (MWCNTs@SnO(2)-Au) composite was
      synthesized by a chemical route. The structure and composition of the
      MWCNTs@SnO(2)-Au composite were confirmed by means of transmission electron
      microscopy, X-ray photoelectron and Raman spectroscopy. Due to the good
      electrocatalytic property of MWCNTs@SnO(2)-Au composite, a glucose biosensor was
      constructed by absorbing glucose oxidase (GOD) on the hybrid material. A direct
      electron transfer process is observed at the MWCNTs@SnO(2)-Au/GOD-modified glassy
      carbon electrode. The glucose biosensor has a linear range from 4.0 to 24.0mM,
      which is suitable for glucose determination by real samples. It should be
      worthwhile noting that, from 4.0 to 12.0mM, the cathodic peak currents of the
      biosensor decrease linearly with increasing the glucose concentrations in human
      blood. Meanwhile, the resulting biosensor can also prevent the effects of
      interfering species. Moreover, the biosensor exhibits satisfying reproducibility,
      good operational stability and storage stability. Therefore, the MWCNTs@SnO(2)
      Au/GOD biocomposite could be promisingly applied to determine blood sugar
      concentration in the practical clinical analysis.

PMID- 19767195
TI  - Single bead-based electrochemical biosensor.
AB  - A simple, robust, single bead-based electrochemical biosensor was fabricated and
      characterized. The sensor's working electrode consists of an electrochemically
      etched platinum wire, with a nominal diameter of 25 microm, hermetically heat
      fusion sealed in a pulled glass capillary (micropipette). The sealing process
      does not require any epoxy or glue. A commercially available, densely
      functionalized agarose bead was mounted on the tip of the etched platinum wire.
      The use of a pre-functionalized bead eliminates the tedious and complicated
      surface functionalization process that is often the bottleneck in the development
      of electrochemical biosensors. We report on the use of a biotin agarose bead
      based, micropipette, electrochemical (Bio-BMP) biosensor to monitor H(2)O(2)
      concentration and the use of a streptavidin bead-based, micropipette,
      electrochemical (SA-BMP) biosensor to detect DNA amplicons. The Bio-BMP
      biosensor's response increased linearly as the H(2)O(2) concentration increased
      in the range from 1 x 10(-6) to 1.2 x10(-4)M with a detection limit of 5 x 10(
      7)M. The SA-BMP was able to detect the amplicons of 1pg DNA template of B. Cereus
      bacteria, thus providing better detection sensitivity than conventional gel-based
      electropherograms.

PMID- 19767196
TI  - Exploring conformational modes of macromolecular assemblies by multiparticle cryo
      EM.
AB  - Single particle cryo-electron microscopy (cryo-EM) is a technique aimed at
      structure determination of large macromolecular complexes in their unconstrained,
      physiological conditions. The power of the method has been demonstrated in
      selected studies where for highly symmetric molecules the resolution attained
      permitted backbone tracing. However, most molecular complexes appear to exhibit
      intrinsic conformational variability necessary to perform their functions.
      Therefore, it is now increasingly recognized that sample heterogeneity
      constitutes a major methodological challenge for cryo-EM. To overcome it
      dedicated experimental and particularly computational multiparticle approaches
      have been developed. Their applications point to the future of cryo-EM as an
      experimental method uniquely suited to visualize the conformational modes of
      large macromolecular complexes and machines.

PMID- 19767197
TI  - Neuroblastoma in the newborn. A study of the Italian Neuroblastoma Registry.
AB  - AIM: Presenting features, treatment and outcome of 134 newborns with
      neuroblastoma diagnosed over a 27-year period are described. METHODS: Analyses
      were performed on the entire cohort and on patients distributed over three
      periods of diagnosis. RESULTS: Twenty-seven tumours (20.1%) were detected
      prenatally. Localised disease prevailed (65.7%) with an increase of stage 1
      patients over time from 18.8% to 46.5%. Disseminated disease accounted for 34.3%
      of tumours with only one stage 4 and 45 stage 4S. Five-year overall survival (OS)
      of the entire cohort was 88.3%. Five/88 patients with localised disease died,
      including three who died of complications (OS, 95.3%). The only stage 4 patient
      survived. Eleven/45 stage 4S patients died, including 7/18 symptomatic and 4/27
      asymptomatic (OS, 74.1%). CONCLUSION: The outcome of neuroblastoma in newborns is
      excellent. In localised tumours, surgery-related deaths outnumbered deaths due to
      disease. Symptomatic stage 4S patients were at greater risk of dying.

PMID- 19767198
TI  - Pegylated liposomal doxorubicin, an effective, well-tolerated treatment for
      refractory aggressive fibromatosis.
AB  - BACKGROUND: Aggressive fibromatosis (AF) or desmoid tumour is a monoclonal
      proliferation which is locally invasive but does not metastasize. If local
      treatment fails to control the disease, systemic treatment with anti-oestrogens,
      non-steroidal anti-inflammatory drugs (NSAIDs) or chemotherapy can be used.
      Recent reports indicate that pegylated liposomal doxorubicin (PLD) is effective.
      METHODS: Twelve patients with AF received PLD between February 2006 and May 2009.
      PLD was administered intravenously (iv) at 50mg/m(2) over 1h every 4 weeks.
      RESULTS: The female/male ratio was 11:1 and median age at presentation was 29
      years (range 3-53). Objective response (PR) was achieved in 4 (36%) of 11
      patients. In one case ongoing shrinkage of the tumour was observed for over 12
      months and partial remission was achieved at 14 months after the completion of
      treatment. Seven patients achieved stable disease. One patient is currently
      undergoing chemotherapy. Clinical benefit in terms of pain relief, improved
      mobility or cosmesis was observed in 11 patients. Nine patients (75%) had no
      evidence of progression at the end of this follow-up period and disease control
      has ranged from 7 to 39 months with a median of 14 months. The most severe
      toxicities observed were palmar-plantar erythema (4) and mucositis (3). In 6
      cases (55%) toxicity resulted in dose reduction. CONCLUSION: This is the largest
      series of patients with AF receiving PLD reported to date. PLD as a single agent
      therapy has acceptable toxicity and highly promising activity in unresectable AF
      and may provide long-term clinical benefit in some patients.

PMID- 19767199
TI  - Expert opinion in melanoma: the sentinel node; EORTC Melanoma Group
      recommendations on practical methodology of the measurement of the microanatomic
      location of metastases and metastatic tumour burden.
AB  - The sentinel node (SN) status has been recognised to be the most important
      prognostic factor in melanoma. Many studies have investigated additional factors
      to further predict survival/lymph node involvement. The EORTC Melanoma Group (MG)
      has formulated the following question: How should we report the microanatomic
      location and SN tumour burden? The EORTC MG recommends the following: the EORTC
      MG SN pathology protocol or a similarly extensive protocol, which has also been
      proven to be accurate, should be used. Only measure what you can see not what you
      presume. Cumulative measurements decrease the accuracy and reproducibility of
      measuring. The most reproducible measure is a single measurement of the maximum
      diameter of the largest lesion in any direction (1-D). If there is any
      infiltration into the parenchyma, this lesion can no longer be considered solely
      subcapsular. Reporting of the microanatomic location of metastases should be an
      assessment of the entire sentinel node, not only of the largest lesion.
      Multifocality reflects a scattered metastatic pattern, not to be confused with
      multiple cohesive foci, which fall under the regular location system. A
      subcapsular metastasis should have a smooth usually curved outline, not ragged or
      irregular. We recommend all pathologists to report the following items per
      positive SN for melanoma patients: the microanatomic location of the metastases
      according to Dewar et al. for the entire node, the SN Tumour Burden according to
      the Rotterdam Criteria for the maximum diameter of the largest metastasis
      expressed as an absolute number, and the SN Tumour Burden stratified per
      category; <0.1mm or 0.1-1.0mm or >1.0mm.

PMID- 19767200
TI  - Heterologous expression of phosphoenolpyruvate carboxylase enhances the phosphate
      solubilizing ability of fluorescent pseudomonads by altering the glucose
      catabolism to improve biomass yield.
AB  - The Synechococcus elongatus PCC 6301 phosphoenolpyruvate carboxylase (ppc) gene
      was constitutively overexpressed in fluorescent pseudomonads, to increase the
      supply of oxaloacetate, a crucial anabolic precursor and an intermediate in
      biosynthesis of organic acids implicated in phosphate (P) solubilization.
      Pseudomonas fluorescens ATCC 13525, transformed with pAB3 plasmid containing the
      ppc gene showed a 14-fold increase in PPC activity under P-sufficiency resulting
      in increased carbon flow through the direct oxidative pathway and reduced
      metabolic overflow. Under P-limitation, contribution of the direct oxidative
      pathway significantly increased in P. fluorescens ATCC 13525; however, ppc
      overexpression enhanced glucose catabolism through intracellular phosphorylative
      pathway. These results correlated with gluconic, pyruvic and acetic acid levels
      as well as the activities of key glucose catabolic enzymes. Irrespective of the P
      status, ppc overexpression improved biomass yield without altering growth rate,
      resulting in improved P- solubilizing abilities of P. fluorescens ATCC 13525 as
      well as of the wheat rhizosphere fluorescent pseudomonads isolates Fp585, P109
      and Fp315. Collectively, ppc overexpression reversed the P-status dependent
      glucose distribution between the direct oxidative and phosphorylative pathways of
      glucose catabolism in P. fluorescens ATCC 13525 and presents a feasible genetic
      engineering approach for developing efficient P-solubilizing bacteria.

PMID- 19767201
TI  - Process modeling and analysis of pulp mill-based integrated biorefinery with
      hemicellulose pre-extraction for ethanol production: a comparative study.
AB  - Pulp and paper mills represent a major platform to use more effectively an
      abundant, renewable bio-resource - wood. Modification of the modern day pulp
      mills into integrated forest biorefineries (IFBR) presents an excellent
      opportunity to produce, in addition to valuable cellulose fiber, co-products
      including fuel grade ethanol and additional energy, thus resulting in increased
      revenue streams and profitability and potentially lower the greenhouse gas
      emissions. A process model to simulate the integrate forest biorefinery
      manufacturing pulp and other co-products has been developed. This model has been
      used to compare three integrated biorefinery scenarios: the conventional Kraft
      pulping process, the pulp mill-based IFBR with hemicelluloses extraction prior to
      pulping for ethanol production, and the pulp mill-based IFBR with both pre
      extracted hemicelluloses and the short fiber for ethanol production. Based on a
      fixed feedstock throughput of 2000 dry Mg wood/day, results show that the pulp
      mill-based IFBR with both pre-extracted hemicelluloses and the short fiber
      cellulose converted to ethanol can produce 0.038 MM m(3) (10.04 MM gal) ethanol
      per year at a minimum ethanol selling price (MESP) of $491/m(3) ($1.86/gal). The
      economic feasibility of IFBR can be further improved by using further
      improvements in the pre-extraction process, other biomass such as corn stover for
      producing ethanol, and taking advantage of the economies of scale.

PMID- 19767202
TI  - Influence of compost amendment on microbial community and ecotoxicity of
      hydrocarbon-contaminated soils.
AB  - The influence of a high quality compost amendment on two soils contaminated with
      diesel oil and polycyclic aromatic hydrocarbons, PAHs, respectively, was
      evaluated, with respect to contaminant biodegradation, microbial community
      composition and soil toxicity and genotoxicity. For each of the two soils, two 20
      kg biopiles were set up, one without amendments and one compost-amended. GC/FID
      analyses revealed that compost was effective in enhancing biodegradation of
      diesel oil and of four-ring PAHs. It also influenced microbial community
      composition, as inferred by ARDRA analyses and partial sequencing of 16S rDNA of
      clones from libraries constructed from each soil sample. Microtox analyses on
      soil aqueous saline extracts and Solid Phase Tests showed some toxicity reduction
      due to compost addition, while the Comet assay, performed on coelomocytes of
      earthworms exposed to contaminated soils, did not show genotoxicity reduction. In
      general, the use of compost amendment to hydrocarbon-contaminated soils in a
      bioremediation process proved to be effective for depletion of contaminants and
      reduction of toxicity.

PMID- 19767203
TI  - Bio-refinery system of DME or CH4 production from black liquor gasification in
      pulp mills.
AB  - There is great interest in developing black liquor gasification technology over
      recent years for efficient recovery of bio-based residues in chemical pulp mills.
      Two potential technologies of producing dimethyl ether (DME) and methane (CH(4))
      as alternative fuels from black liquor gasification integrated with the pulp mill
      have been studied and compared in this paper. System performance is evaluated
      based on: (i) comparison with the reference pulp mill, (ii) fuel to product
      efficiency (FTPE) and (iii) biofuel production potential (BPP). The comparison
      with the reference mill shows that black liquor to biofuel route will add a
      highly significant new revenue stream to the pulp industry. The results indicate
      a large potential of DME and CH(4) production globally in terms of black liquor
      availability. BPP and FTPE of CH(4) production is higher than DME due to more
      optimized integration with the pulping process and elimination of evaporation
      unit in the pulp mill.

PMID- 19767204
TI  - Microwave assisted thermal treatment of defective coffee beans press cake for the
      production of adsorbents.
AB  - Defective coffee press cake, a residue from coffee oil biodiesel production, was
      evaluated as an adsorbent for removal of basic dyes (methylene blue--MB) from
      aqueous solutions. The adsorbent was prepared by microwave treatment, providing a
      significant reduction in processing time coupled to an increase in adsorption
      capacity in comparison to conventional carbonization in a muffle furnace. Batch
      adsorption tests were performed at 25 degrees C and the effects of particle size,
      contact time, adsorbent dosage and initial solution pH were investigated.
      Adsorption kinetics was better described by a second-order model. The
      experimental adsorption equilibrium data were fitted to Langmuir, Freundlich and
      Tempkin adsorption models, with Langmuir providing the best fit. The results
      presented in this study show that microwave activation presents great potential
      as an alternative method in the production of adsorbents.

PMID- 19767205
TI  - Isolation of a Bacillus strain producing ketone reductase with high substrate
      tolerance.
AB  - Target reaction-oriented screening from soil samples yielded a ketone reductase
      producing Bacillus sp., strain ECU0013, which exhibits excellent
      stereoselectivity, high substrate tolerance and is capable of regenerating the
      required cofactor with glucose as a co-substrate. Whole-cells catalyzed the
      asymmetric reduction of 2-chloro-1-phenylethanone (50mM) to (R)-2-chloro-1
      phenylethanol with a 93.3% conversion rate and 99% e.e. (enantiomeric excess). A
      variety of ketones were enantioselectively reduced by resting cells, giving
      corresponding chiral alcohols with good to excellent e.e. values. These results
      suggest the potential of this strain for the industrial production of chiral
      halogenated aromatic alcohols.

PMID- 19767206
TI  - Synthesis and in vitro autoradiographic evaluation of a novel high-affinity
      radioiodinated ligand for imaging brain cannabinoid subtype-1 receptors.
AB  - There is strong interest to study the involvement of brain cannabinoid subtype-1
      (CB1) receptors in neuropsychiatric disorders with single photon emission
      computed tomography (SPECT) and a suitable radioligand. Here we report the
      synthesis of a novel high-affinity radioiodinated CB1 receptor ligand ([125I]8,
      [125I]1-(2-iodophenyl)-4-cyano-5-(4-methoxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole
      3-carboxylate, [125I]SD7015). By autoradiography in vitro, [125I]8 showed
      selective binding to CB1 receptors on human brain postmortem cryosections and now
      merits labeling with iodine-123 for further evaluation as a SPECT radioligand in
      non-human primate.

PMID- 19767207
TI  - Synthesis and SAR of 2-phenyl-1-sulfonylaminocyclopropane carboxylates as ADAMTS
      5 (Aggrecanase-2) inhibitors.
AB  - A series of 1-sulfonylaminocyclopropanecarboxylates was synthesized as ADAMTS-5
      (Aggrecanase-2) inhibitors. After an intensive investigation of the central
      cyclopropane core including its absolute stereochemistry and substituents, we
      found compound 22 with an Agg-2 IC50=7.4 nM, the most potent ADAMTS-5 inhibitor
      reported so far.

PMID- 19767208
TI  - Discovery and optimization of novel 4-[(aminocarbonyl)amino]-N-[4-(2
      aminoethyl)phenyl]benzenesulfonamide ghrelin receptor antagonists.
AB  - This Letter describes optimization of ghrelin receptor antagonists and inverse
      agonists starting from a screening hit.

PMID- 19767209
TI  - Combined transarterial, transvenous, and direct puncture of the cavernous sinus
      to cure a traumatic carotid cavernous fistula.
AB  - Direct carotid cavernous fistulas (CCF) are generally well managed by simple
      endovascular treatment. We report an 8-year-old boy who required subsequent
      direct puncture of the cavernous sinus to completely obliterate the residual
      fistula after both transarterial and transvenous embolization had been performed.
      He presented with a mild right frontal headache, congestion of the right
      conjunctiva, blurred vision, and photophobia. Cerebral angiography demonstrated a
      right direct CCF. The patient underwent transarterial and transvenous
      embolization of the cavernous sinus (CS) with Gugliemi detached coils (GDCs), but
      a residual shunt persisted. Two days later, another session of embolization by
      direct puncture of the CS with GDCs was performed after failure to navigate
      through the superior ophthalmic vein which was partially occupied by previously
      deployed coils. Immediate control angiography showed complete obliteration of the
      fistula and the patient's symptoms rapidly resolved. This is the first report of
      a patient with a CCF who required three combined approaches - transarterial,
      transvenous, and direct puncture of the CS - to achieve complete closure of the
      complexed shunt.

PMID- 19767210
TI  - A mesenteric paraganglioma.
AB  - Mesenteric paraganglioma is a solitary primary paraganglioma that occurs in the
      mesentery. It is a rare and unusual tumor, especially in non-typical sites such
      as the inferior mesenteric artery. We incidentally diagnosed a pelvic mass in a
      22-year-old woman, who had not experienced vomiting, headache or hypertension.
      She was found to have an immobile solid mass on the left side of her pelvis,
      adjacent to the upper segment of the uterus. CT scans revealed a well-defined
      solid and cystic ovoid mass adjacent to the sigmoid colon and the uterus. Tumor
      markers were within the normal range. Surgery was performed to completely remove
      the mass. An intra-operative frozen section biopsy showed a benign cystic tumor.
      Histopathological examination indicated that it was a paraganglioma of the
      mesentery. Repeat CT examination did not reveal any local recurrence or distant
      metastasis during the 13-month follow-up period.

PMID- 19767211
TI  - Synthesis and structure-activity relationships of dehydroaltenusin derivatives as
      selective DNA polymerase alpha inhibitors.
AB  - Herein, we describe the synthesis and structure-activity relationships of
      dehydroaltenusin derivatives as inhibitors of a mammalian DNA polymerase alpha.
      We have newly synthesized nine dehydroaltenusin derivatives modified at the side
      chains or benzoquinone moiety. We also achieved the first synthesis of
      desmethylaltenusin and desmethyldehydroaltenusin, metabolites of Alternaria sp.
      or Talaromyces flavus, respectively. Among all synthesized derivatives,
      demethoxydehydroaltenusin was the most selective inhibitor of DNA polymerase
      alpha. The o-hydroxy-p-benzoquinone (2-hydroxycyclohexa-2,5-dienone) moiety is
      essential for the inhibition of DNA polymerases. Substitution at the 5-position
      of dehydroaltenusin is important for the inhibitory potency. Because
      dehydroaltenusin is conjugated with N-acetylcysteine methyl ester at the o
      hydroxy-p-benzoquinone moiety, one or more cysteine residues of DNA polymerase
      alpha may act as a target for this compound.

PMID- 19767212
TI  - Aprotinin in lung transplantation is associated with an increased incidence of
      primary graft dysfunction.
AB  - OBJECTIVE: Aprotinin has been widely used to reduce bleeding and transfusion
      requirements in cardiac surgery and in lung transplantation. A recent study found
      a significant reduction in severe (grade III) primary graft dysfunction (PGD) in
      lung transplantation where aprotinin had been used. However, recently, concerns
      regarding the safety of aprotinin have been raised, and the future use of
      aprotinin is uncertain. In our institution, aprotinin has been widely used in
      cardiac surgery and transplantation. We decided to review our lung transplant
      caseload to investigate the impact of aprotinin on PGD and mortality and to guide
      our future clinical use of this antifibrinolytic. METHODS: A retrospective review
      of prospectively collected data on 213 consecutive patients who underwent single-
      or double-lung transplantation was performed. Ninety-nine patients, who received
      aprotinin, were compared with 114 patients who did not. The main outcome
      variables analysed were development of primary graft dysfunction, renal
      impairment and mortality. RESULTS: Aprotinin was associated with a significantly
      increased risk of PGD in the first 48 h postoperatively (p=0.01). CONCLUSIONS: In
      conclusion, although the benefits of aprotinin on blood loss are well
      established, this study does not provide support for the use of aprotinin to
      reduce PGD in lung transplantation and indicates that aprotinin may in fact have
      a detrimental effect.

PMID- 19767213
TI  - Intraosseous lipoma of the rib.

PMID- 19767214
TI  - Surgery for mesothelioma: MARS landing and future missions.

PMID- 19767215
TI  - Hypersensitivity reactions to aprotinin re-exposure in paediatric surgery.
AB  - OBJECTIVE: Hypersensitivity to aprotinin is low (1-3%) but more likely with re
      exposure. The manufacturer issued a black box warning which lists aprotinin re
      exposure within 1 year of prior exposure as a contraindication. We investigated
      the temporal relationship between re-exposure interval and hypersensitivity in
      children. METHODS: With Human Research Review Board approval, charts of all
      patients exposed to aprotinin during cardiac surgery were reviewed. We extracted
      data for re-exposure interval and hypersensitivity to skin tests, intravenous
      test dosing or infusion of the loading dose. We defined systemic hypersensitivity
      as haemodynamic instability, respiratory symptoms or diffuse skin reaction
      temporally related to exposure. RESULTS: From March 1994 to June 2007, there were
      a total of 2333 aprotinin exposures in 1824 patients. A total of 509 re-exposures
      occurred in 381 patients: 280 in 244 patients with early (within 1 year) re
      exposure and 229 in 222 patients with late (after 1 year) re-exposure. Thirteen
      systemic hypersensitivity reactions occurred in the 509 re-exposures (2.6%): two
      during skin testing and 11 during the loading dose. Although the incidence of
      local hypersensitivity was increased with early re-exposure (6/280 or 2.1% vs
      0/229, p=0.019), the incidence of the systemic reaction was not different between
      early and late re-exposures (6/280 or 2.1% (CI 0.8-4.6%) vs 7/229 or 3.1% (CI 1.2
      6.2%), p=0.6). Six patients with a previous hypersensitivity reaction had an
      additional re-exposure to aprotinin; one of these patients had a systemic
      reaction during the third exposure. CONCLUSION: The incidence and type of
      hypersensitivity to aprotinin re-exposure in our cohort is consistent with
      previous reports. Repeat exposure within 1 year did not increase the risk of
      systemic hypersensitivity.

PMID- 19767216
TI  - Absolute and relative risk prediction in patients candidate to isolated aortic
      valve replacement: should we change our mind?
AB  - OBJECTIVE: The European System for Cardiac Operative Risk Evaluation (EuroSCORE)
      calculator performance in 30-day outcome prediction after isolated aortic valve
      replacement (AVR) was evaluated to assess its absolute reliability and usefulness
      as selection criteria to percutaneous aortic valve implantation (PAVI). METHODS:
      We carried out a retrospective statistical analysis on 379 patients (group 0)
      consecutively submitted to isolated AVR in the past 10 years of surgical
      activity. We discriminated two periods of 5 years each, so we considered two
      subgroups of patients: group 1 (200 patients operated during 1999-2003); group 2
      (179 patients operated during 2004-2008). We used receiver operating
      characteristics (ROC) curves for discriminatory power analysis. Model calibration
      was evaluated with the Hosmer-Lemeshow goodness-of-fit test and Pseudo R(2)
      analysis. RESULTS: The overall expected mortality rate at the logistic calculator
      was 9.37% compared with an observed 10-year mortality of 5.2% (p=0.006). Absolute
      risk prediction in group 1 fitted the observed outcome (p=0.24) while expected
      mortality in group 2 was significantly higher than observed (p=0.005). Applying
      threshold values used as PAVI selection criteria (logistic EuroSCORE >20 or >15),
      against 29% and 24.3% expected mortality rate, respectively, we registered a
      significant difference in the observed values (11.4%, p=0.022; 8.6%, p=0.005,
      respectively). The Hosmer-Lemeshow test demonstrated a lack of model fit in the
      overall group (p=0.019). ROC analysis revealed a sufficient discriminatory power
      for either total population (logistic area under curve (AUROC) 0.706; 95%
      confidence interval (CI): 0.604-0.809; p=0.002) and group 1 (logistic AUROC
      0.752; 95% CI: 0.643-0.860; p=0.002). Group 2 showed a lack of risk
      stratification (logistic AUROC 0.613; 95% CI: 0.401-0.824; p=0.348). CONCLUSIONS:
      EuroSCORE appears to be an invalid model in absolute and relative risk prediction
      for isolated AVR. On this basis, its use in selecting candidates to PAVI should
      be carefully weighted. Correct stratification and sufficient calibration of
      absolute risk estimate of high-risk patients are, therefore, mandatory in the aim
      of assigning those patients who show risk factors really responsible for the
      worst surgical outcome to new techniques. The goal should be reached by exploring
      the weight of each independent predictor of death in each single institution
      involved in PAVI procedures, evaluating local surgical results in terms of
      absolute risk and analysing those variables significantly affecting relative
      risk.

PMID- 19767217
TI  - Low cardiopulmonary bypass perfusion temperatures are associated with acute
      kidney injury following coronary artery bypass surgery.
AB  - OBJECTIVE: Acute kidney injury (AKI) is a common complication after coronary
      artery bypass surgery (CABG). The role of hypothermia in postoperative renal
      function remains controversial. We set out to examine the effect of varying
      cardiopulmonary bypass (CPB) temperatures on early postoperative renal function.
      METHODS: Patients undergoing first-time CABG between 2002 and 2006 and without
      evidence of preoperative renal insufficiency (estimated creatinine clearance
      >or=50 ml min(-1), calculated by the Cockcroft-Gault formula) were studied.
      Medical history and intra-operative variables, including lowest nasopharyngeal
      and arterial CPB perfusion temperatures, were collected prospectively. Primary
      endpoint was the development of early postoperative AKI (defined as creatinine
      clearance <50 ml min(-1)), which was assessed using multivariate and propensity
      score analyses. RESULTS: This study included 1072 patients. AKI occurred in 175
      (16%). Univariate analysis demonstrated that lower arterial CPB perfusion
      temperatures, and not nasopharyngeal ones, were significantly associated with
      renal dysfunction following CABG. Multivariate regression analysis identified
      reduced arterial perfusion temperature as an independent risk factor for AKI
      (odds ratio (OR) 0.92, 95% confidence interval (CI): 0.86-0.98, p=0.012), along
      with age (OR 1.07, 95% CI: 1.04-1.10, p<0.001) and depressed preoperative
      creatinine clearance (OR 0.89, 95% CI: 0.87-0.91, p<0.001). Propensity score
      adjustment confirmed that lower CPB perfusion temperatures (<27 degrees C) were
      associated with postoperative AKI (OR 1.66, 95% CI: 1.16-2.39, p=0.0056).
      CONCLUSIONS: Lower CPB perfusion temperatures are significantly associated with
      AKI following CABG. In addition to the known age-related decline in renal
      function, it appears that hypothermia may contribute to renal injury during
      cardiac surgery.

PMID- 19767218
TI  - Auditory evoked blink reflex and posterior auricular muscle response:
      observations in patients with HFS and PFS.
AB  - Our goal was to investigate the characteristics of the auditory brainstem
      reflexes in patients with hemifacial spasm (HFS) and postparalytic facial
      syndrome (PFS). The spasm activities and responses by supraorbital and auditory
      stimuli were recorded from the orbicularis oculi, the posterior auricular and the
      mentalis muscles in 27 HFS and 21 PFS patients. The results were compared with
      those of 20 controls. Blink reflex (BR) was obtained by supraorbital stimulation
      in normal controls and on both sides of HFS and PFS patients whereas sound evoked
      bilateral auditory blink reflex (ABR) in 96.3%, 90.5% and 100%, respectively.
      Both BR and ABR showed synkinetic spread on symptomatic sides in all patients.
      The posterior auricular muscle response (PAMR) was observed bilaterally in 59.3%,
      42.9% and 75.0% of groups, respectively. However, there was no synkinetic spread
      of PAMR. Since PAMR does not show synkinetic spread even in the presence of
      synkinetic spread of ABR and BR, we may suggest that a distal origin may be
      responsible of the synkinetic spread, or PAM is probably governed by a smaller
      nucleus in the brainstem. Thus it may be speculated that its excitability is
      insufficient to stimulate the ABR nucleus, whereas the reverse process is
      possible.

PMID- 19767219
TI  - MicroRNA-221 silencing predisposed human bladder cancer cells to undergo
      apoptosis induced by TRAIL.
AB  - OBJECTIVES: Bladder cancer is the most common type of urologic cancer in Chinese
      males. The 5-year survival rate of advanced bladder cancer is approximately 20%
      40%. There is an obvious urgent need for novel and effective therapies against
      bladder cancer. MicroRNAs (miRNAs) are a recently discovered class of noncoding
      RNAs; suppressing miRNA-221 might prove beneficial in several cancers. To explore
      novel and effective therapies against bladder cancer, we explored the effects of
      miRNA-221 silencing on the survival of bladder cancer cells. MATERIALS AND
      METHODS: Northern blot analysis was used to determine miRNA-221 expression levels
      in bladder cancer T24 cells, RT4 cells and human normal urothelial cells. miRNA
      221 was silenced with antisense oligonucleotides in T24 cells and pro-apoptotic
      effect of necrosis factor related apoptosis-inducing ligand (TRAIL) on miRNA-221
      silenced cells was assessed with flow cytometry. The p27(kip1) protein expression
      in miRNA-221-silenced cells exposed to TRAIL was detected by Western blotting.
      The role of miRNA-221 silencing on T24 cell cycle phase distribution was
      investigated through flow cytometric analysis. RESULTS: Human miRNA-221 was
      significantly up-regulated in bladder cancer T24 cells and RT4 cells compared to
      human normal urothelial cells. T24 cell was TRAIL-resistant cell line. MiRNA-221
      silencing predisposed T24 cells to undergo apoptosis induced by TRAIL and
      resulted in an up-modulation of cyclin-dependent kinase inhibitor p27Kip1. MiRNA
      221 suppression promoted the activation of caspase 3 induced by TRAIL in T24
      cells. CONCLUSIONS: MiRNA-221 silencing rendered human bladder cancer T24 cells
      to undergo apoptosis induced by TRAIL. Our findings suggest a potential role of
      suppressing miRNA-221 in human bladder cancer therapy.

PMID- 19767220
TI  - Fibulin-5 is down-regulated in urothelial carcinoma of bladder and inhibits
      growth and invasion of human bladder cancer cell line 5637.
AB  - PURPOSE: The expression of fibulin-5 was investigated in urothelial carcinomas of
      bladder and in normal bladder samples. The effects of fibulin-5 on cell
      proliferation, motility, and invasion were further explored in bladder cancer
      cell line 5637. MATERIALS AND METHODS: The expression of fibulin-5 in 20 bladder
      carcinoma samples and 7 normal bladder samples were detected by Western blot.
      Fibuin-5 cDNA was cloned into p-EGFP-N1 vector and transfected into bladder
      cancer cell line 5637. Growth curves were estimated by the 3-[4,5-dimethylthiazol
      2-yl]-2,5-diphenyl-tetrazolium bromide assay and cell number count. The migration
      and invasion of the transfected cells and the control cells were measured by
      Boyden chamber assay. RESULTS: Compared with 1.16 +/- 0.28 in the normal control,
      the mean +/- SD expression of fibulin-5 in low grade tumors and high grade tumors
      were 0.57 +/- 0.32 and 0.44 +/- 0.42 (P = 0.002 and P = 0.018, respectively),
      while the expression in Ta-T1 tumors and T2+ tumors were 0.55 +/- 0.31 and 0.49
      +/- 0.43 (P = 0.002 and P = 0.015, respectively). The differences between low
      grade and high grade tumors or Ta-T1 and T2+ tumors were not statistically
      significant (P = 0.362 and P = 0.589, respectively). The growth rate of the
      fibulin-5 transfected GFP-F5 cells was remarkably reduced than that of the
      untransfected cells or the empty vector transfected GFP-t cells. Besides,
      compared with control cells, the GFP-F5 cells showed significant inhibition of
      cell invasion with slight inhibition of cell migration. CONCLUSIONS: Fibulin-5 is
      down-regulated in urothelial carcinoma of bladder and acts as a tumor suppressor
      gene by inhibiting proliferation and invasion of bladder cancer cells.

PMID- 19767221
TI  - Significance of nuclear grade and tumor size in Korean patients with chromophobe
      renal cell carcinoma: a comparison with conventional renal cell carcinoma.
AB  - OBJECTIVES: To analyze the clinical behavior of chromophobe renal cell carcinoma
      (RCC) in Korean patients. MATERIALS AND METHODS: A total of 657 patients with
      conventional RCC and 71 with chromophobe RCC were included in the analysis. The
      median follow-up for all patients was 44 months (95% confidence interval, 10 to
      126). RESULTS: Patients with chromophobe RCC differed significantly from those
      with conventional RCC on the following parameters: a greater female ratio (P =
      0.019), less advanced TNM stage (P = 0.004), and higher Fuhrman nuclear grade (P
      < 0.001). There was no statistical difference with regard to age and tumor
      diameter. The 5- and 10-year disease-specific survival rates in patients with
      chromophobe RCC (92.9% and 92.9%) were higher than in patients with conventional
      RCC (84.9% and 79.8%). When patients were divided according to T stage, Fuhrman's
      grade, and tumor size for the subgroup analysis, disease-specific survival
      probabilities of chromophobe RCC were higher in only tumors with a high Fuhrman's
      grade (G3/G4) (P = 0.002) and larger than 4 cm (P = 0.025). The multivariate
      analysis showed that the histologic type was not an independent predictor of
      disease-specific survival. CONCLUSIONS: Although Korean patients with chromophobe
      RCC had a better survival probability than patients with conventional RCC, the
      histologic type was not an independent predictor of survival probability. In
      addition, our findings suggest that chromophobe RCC has a better survival
      probability than conventional RCC in patients with Fuhrman's grade 3 to 4 or with
      a tumor diameter > 4.0 cm.

PMID- 19767222
TI  - Conservative management of type 2 endoleaks is not associated with increased risk
      of aneurysm rupture.
AB  - OBJECTIVE: Endovascular repair (EVAR) of abdominal aortic aneurysms (AAAs) has
      led to a reduction in the perioperative mortality when compared with open repair.
      However, re-intervention for complications, such as endoleak, may be required in
      up to 20% of the cases. Controversy exists over the management of type 2
      endoleaks. This study examined the outcomes of patients with type 2 endoleaks
      treated conservatively to inform the ongoing management debate. METHODS: All
      patients with a confirmed type 2 endoleak after EVAR for an infrarenal AAA were
      included in the study. Data regarding device details, endoleak and time point,
      aneurysm sac growth, intervention and outcome were collected retrospectively from
      case notes and the vascular research database. RESULTS: Forty-one type 2
      endoleaks were seen in 369 EVARs performed for infrarenal AAA between March 1994
      and June 2006. Twenty-five were isolated type 2 endoleaks and 16 occurred in
      conjunction with other endoleaks. Of the 25 isolated type 2 endoleaks, 18 (72%)
      patients demonstrated no increase in sac size, six (24%) patients showed an
      enlargement of the sac and one patient was lost to follow-up. Only one patient
      underwent intervention for an isolated type 2 endoleak. After a mean follow-up
      period of 4 years, approximately half of the patients (48%) remain under
      observation (with an enlarging or stable sac), whilst the others (48%) have
      spontaneously sealed. Only five patients under surveillance (20%) have an
      enlarging sac. There were no ruptured aneurysms or aneurysm-related deaths and no
      patients required conversion to open repair. CONCLUSIONS: In this study, a policy
      of regular surveillance for type 2 endoleaks was not associated with any adverse
      events. We therefore advocate the conservative approach for type 2 endoleaks.

PMID- 19767223
TI  - Induced-fit docking studies of the active and inactive states of protein tyrosine
      kinases.
AB  - Inhibition of tyrosine kinases (such as the epidermal growth factor receptor,
      EGFR, and/or Abelson leukemia virus protein kinase, ABL) represents a major
      advancement in the treatment of solid tumors, supported by the clinical
      administration of gefitinib, erlotinib, imatinib, and dasatinib. The
      identification of the binding interactions in the EGFR/ligands and the
      ABL/ligands complexes can facilitate the structure-based design of new tyrosine
      kinase inhibitors. We carried out induced-fit docking studies of 18 structurally
      diverse kinase inhibitors against the EGFR, the active and inactive states of the
      ABL protein. Our docking data show that the induced-fit docking (IFD) protocol
      can successfully reproduce the native poses of ligands from different sources.
      The binding interactions and the docked poses are consistent with the available
      experimental data. Our results indicate that imatinib is a weak binder to the
      active state of ABL but a strong binder to EGFR. The increased sensitivity of
      erlotinib to EGFR might be attributed to Cys797 of EGFR. In addition to Cys797,
      other important residues for kinase inhibitor design include Thr790, Met793,
      Lys745 and Asp855 of EGFR; and Thr315, Met318, Asp381 and Glu286 of the ABL. The
      minimum number of H-bonds required for the ligand binding provides a reasonable
      explanation to the effectiveness of nilotinib against most imatinib resistant
      mutants.

PMID- 19767224
TI  - High prevalence of structural heart disease in children with cblC-type
      methylmalonic aciduria and homocystinuria.
AB  - OBJECTIVE: To characterize the frequency and nature of cardiovascular defects in
      patients with CblC-type methylmalonic aciduria and homocystinuria (cblC), an
      inborn error of cobalamin (vitamin B12) metabolism resulting in accumulation of
      methylmalonic acid and homocysteine. STUDY DESIGN: A retrospective observational
      study was conducted investigating 10 patients with cblC ranging in age from 2
      weeks to 24 years (mean 4.4 years +/- 7.5 years, median 0.6 years). All patients
      underwent a complete 2-D echocardiogram including quantitative assessment of left
      ventricular systolic function. RESULTS: Structural heart defects were detected in
      50% of patients with cblC. Heart defects included left ventricular (LV) non
      compaction (3), secundum atrial septal defect (2), muscular ventricular septal
      defect (1), dysplastic pulmonary valve without pulmonary stenosis (1) and mitral
      valve prolapse with mild mitral regurgitation (1). One patient had resolved cor
      pulmonale and right heart failure secondary to pulmonary embolism. All patients
      had quantitatively normal LV systolic function. CONCLUSIONS: Diverse and
      clinically significant structural heart defects appear to be highly prevalent in
      cblC, perhaps due to abnormal DNA and histone methylation during embryogenesis.
      The specific cardiac defects detected in our cohort were variable, and studies
      with a larger number of patients are needed to establish which forms are most
      common. Routine and periodic cardiovascular evaluation may be indicated in
      patients with cblC.

PMID- 19767225
TI  - [Fibrinolysis in acute myocardial infarction in the emergency department of a
      regional hospital].
AB  - Acute myocardial infarction (AMI) is caused by a lack of blood supply due to
      obstruction of a coronary artery causing ischaemia around the heart muscle. The
      patient with AMI usually begins with chest pain, which is sometimes irradiating
      and oppressive, but this is not always decisive, as we will see. It can be
      detected rapidly, or suspicion confirmed by performing an ECG, which in most
      cases will show changes in the ST segment. The diagnosis can be supplemented by
      an analytical study with specific values of creatine kinase and Troponins. Due to
      the long distances that there may be between a level I hospital and a level III
      one, where in many cases, to obtain fibrinolytic treatment. This treatment
      involves administering a fibrinolytic drug to dissolve the clot that clogs the
      coronary artery causing the heart attack. The door-needle time (defined as the
      time between when the patient enters the emergency department to having the first
      puncture for treatment) is very important as the longer the time of onset of AMI,
      fibrinolytic treatment may be contraindicated. The performing of nursing triage
      may be critical for this health problem. Nursing care will also be the key for
      patient care.

PMID- 19767226
TI  - [Coordination between primary and specialist care. Satisfaction with the
      consulting specialist project].
AB  - OBJECTIVE: To find out the level of satisfaction and opinions of doctors on the
      specialist consultant project (SCP) in Area 7. To report on these opinions on the
      difficulties and possible solutions in inter-relationships between of primary
      health care and specialised care. MATERIAL AND METHODS: Transversal descriptive
      study using a self-administered questionnaire. STUDY POPULATION: Doctors working
      in a primary health care district of Madrid (Area 7). VARIABLES: Demographic and
      professional variables, including their satisfaction after the implementation of
      the SCP, their general opinion of SCP, potential benefits and their opinions on
      the difficulties and possible solutions in interrelationships between primary
      health care and specialised care. RESULTS: A total of 170 (56%) doctors working
      in primary health care responded. As regards satisfaction with the SCP, the
      overall score in the evaluation was 8.9, (0 to 10). The majority of primary
      health care doctors (83%) found it easy to contact the specialist and 90% said
      that problems were solved satisfactorily. The telephone was the worst
      communication tool. Only 27% of primary health care doctors said they always
      register SCP activities, and 39% register them almost always. They thought that
      the most useful part of this project was the potential benefit on diagnosis. The
      SCP need score was 9, SCP usefulness 9.1 and priority 8.7. A large majority (74%)
      of primary health care doctors thought it would be of great interest to
      incorporate consultants from other specialisations. The main coordination
      problems found where the lack of communication, and overcrowding. The most valued
      solution to these problems is the computerised clinical history. CONCLUSIONS:
      Doctors are very satisfied with this project. They considered the project to be
      very useful, necessary and a priority, with high potential benefit in several
      areas of patient care. As quality improvement areas we stress the importance of
      continuing to promote SCP, of adequate telephone communications and to assess a
      new easy to fill-in register system.

PMID- 19767227
TI  - [Risk analysis in radiotherapy].
AB  - Radiation therapy was one of the first medical specialties to implement quality
      assurance (QA) programs in clinical practice. These QA programs have mainly
      focused on equipment performance, neglecting human factors. Risk management is a
      relatively new approach in medical disciplines. Methods of evaluation and risk
      management must be identified, applied and adapted to the specificities of this
      domain. Based on the experience of industry, risk management will allow us to
      substantially improve safety and develop our own models of management. Recent
      experiences use these approaches to implement risk management in radiation
      therapy departments.

PMID- 19767228
TI  - Low and stable prevalence of rheumatoid arthritis in northern France.
AB  - OBJECTIVES: Few data are available on the prevalence of rheumatoid arthritis (RA)
      in France. Results of the Epidemiologie des rhumatismes inflammatoires (EPIRHUM
      2) study suggest a lower prevalence in northern France (0.13%) than nationwide
      (0.31%) or in southern France (0.66%). Here, our objective was to confirm the
      lower prevalence of RA in northern France than in the rest of the country or in
      Europe. METHODS: We used the universal health insurance database to identify
      patients with RA in northern France (Nord-Pas de Calais region) in 2005. RESULTS:
      Seven thousand one hundred and twenty-eight patients of the 3,617,224 individuals
      receiving health insurance under the plan for salaried workers in the Nord-Pas de
      Calais region (89.3% of the population in the region) were listed as receiving
      free care for RA, yielding a prevalence of 197.1/100,000 population (female-to
      male ratio, 2.99:1; mean age, 60.8 years). DISCUSSION: The prevalence of RA in
      northern France (0.197% in 2005) is lower than in southern France and northern
      Europe; thus, the prevalence gradient in France is in the opposite direction to
      the decreasing north-to-south gradient previously described in Europe. Although
      environmental and genetic factors involved in the pathogenesis of RA may be
      involved, the main explanation to the low prevalence in northern France may be
      the young age of the population.

PMID- 19767229
TI  - Langerhans cell histiocytosis revealed by painful hip: a case report.
AB  - Langerhans cell histiocytosis is a rare disease in childhood. It has a very
      polymorphous clinical expression, ranging from a single bony disease to a
      multisystemic disease involving vital organs. Prognosis has been improved by use
      of chemotherapy. We report a 2-year-old girl with multifocal Langerhans cell
      histiocytosis of bone and skin, revealed by a pain of the left hip and a limp
      trailing from 2 months. The diagnosis has been established by histological exam.
      The patient received chemotherapy and steroids. Outcome was favourable over 6
      month follow-up. Trailing limp should evoke diagnosis of Langerhans cell
      histiocytosis. Skin biopsy should be preferred to a bone biopsy because of its
      safety.

PMID- 19767230
TI  - [Improvement of operative conditions during a laparoscopic prosthetic sacral
      colpopexy for pelvic organ prolapse repair].
AB  - Actually, the choice of surgical approach for pelvic organ prolapse repair
      depends more on surgeon experience rather than patients characteristics.
      Laparoscopic sacral colpopexy seems to offer complete repair, low morbidity and
      satisfactory anatomic and functional results. This technique requires specially
      trained and experienced surgeons and optimal operative conditions. To improve
      feasibility of laparoscopic sacral colpopexy, we propose a simplified operative
      strategy to optimise this complex procedure.

PMID- 19767231
TI  - Ultrasound assisted green synthesis of bis(indol-3-yl)methanes catalyzed by 1
      hexenesulphonic acid sodium salt.
AB  - 1-Hexenesulphonic acid sodium salt as catalyst for green synthesis of bis(indol-3
      yl)methanes was described. The reaction of indole with various aldehydes in water
      using ultrasound irradiation at ambient temperature for appropriate time using 1
      hexenesulphonic acid sodium salt furnish the desired product in good to excellent
      yield. Utilization of aqueous medium, simple reaction conditions, isolation, and
      purification makes this manipulation very interesting from an economic and
      environmental perspective.

PMID- 19767232
TI  - Large sizes of vertebral body replacement do not reduce the contact pressure on
      adjacent vertebral bodies per se.
AB  - Large implants for vertebral body replacement (VBR) have a large footprint, and
      are normally supported by stronger bone at the rim of the vertebral body. But
      they also necessitate a greater corpectomy defect in the vertebral body
      concerned. In order to study the effect of implant size on contact pressure on
      the adjacent vertebral bodies and thus the risk of implant subsidence, an
      osseoligamentous finite element model of the lumbar spine was employed. The VBR
      was inserted at the level of L4 and additionally stabilized by posterior spinal
      instrumentation. Flat and curved vertebral endplates, small and large corpectomy
      defects, different implant positions and axial preloads as well as normal and
      osteoporotic vertebral bodies were simulated. Contact pressures in the vertebral
      body are increased for a curved vertebral endplate in comparison with a flat one,
      they are increased when an additional implant preload was assumed, and they are
      usually decreased for an osteoporotic vertebra when compared to a non
      osteoporotic one. In some cases the average contact pressures were higher for the
      small-sized VBR, in others for the large-sized one. Our results reveal that from
      the mechanical point of view, a small-sized VBR is not generally disadvantageous.

PMID- 19767233
TI  - In vitro, in vivo and numerical assessment of the working principle of the
      truCCOMS continuous cardiac output catheter system.
AB  - The truCCOMS cardiac output monitor system provides a continuous and
      instantaneous measurement of cardiac output, derived from the amount of energy
      required for heating a filament to maintain a fixed 2 degrees C blood temperature
      difference between two thermistors located distally on a pulmonary artery
      catheter. Clinical studies, however, reported relatively poor accuracy of the
      cardiac output estimation, possibly due to linearly assumed power-cardiac output
      relationship used for calibration of the catheters. We experimentally studied the
      shape of the truCCOMS calibration relationship (i) in a hydraulic bench model of
      the right heart and (ii) in vivo intact animal model. The results showed a
      nonlinear relationship between the power input into the heating element and the
      cardiac output; which could satisfactorily be described with an exponential
      relationship. Comparison of the performance of the same catheters in vitro and in
      vivo showed that the in vitro determined calibration relationship should not be
      used for in vivo measurements. Finally, we also simulated the working principle
      of the catheter using a simplified numerical model of the blood flow and heat
      transfer around the catheter. The computed results also suggested a pronounced
      nonlinear relationship between power and cardiac output in pulsatile conditions.
      We conclude that the observed over- and underestimation of high- and low flows,
      respectively, by the current truCCOMS system is likely to arise from its linear
      calibration relationship. An appropriate calibration scheme accounting for the
      intrinsic nonlinear power-cardiac output relationship and the difference between
      in vitro and in vivo conditions should improve the clinical performance of the
      system.

PMID- 19767234
TI  - Spectroscopic studies on 2-[2-(4-methylquinolin-2-yl)hydrazono]-1,2
      diphenylethanone molecule and its metal complexes.
AB  - The electronic absorption spectra of a hydrazone: 2-[2-(4-methylquinolin-2
      yl)hydrazono]-1,2-diphenylethanone (BHQ) derived from 2-hydrazino-4
      methylquinoline and 1,2-diphenylethan-1,2-dione (benzil) have been studied in
      various solvents of different polarities. The dependence of the band shift
      Deltaupsilon on the solvent parameters viz.D, Z, E(T), DN, AN, alpha, beta and
      pi* was discussed. Also, the effect of pH on the free hydrazone and its Co(II),
      Ni(II) and Cu(II) complexes was studied spectrophotometrically in 75% (v/v)
      dioxane-water in order to determine the dissociation and stability constants. The
      stoichiometry of the formed complexes was determined by three different methods:
      Job's, mole ratio and slope ratio which indicate the formation of 1:2, M:L
      complexes for Co(II) and Cu(II) and 1:1, Ni(II):L. Beer's law is valid in the
      range 0.32-7.04 microg/mL depending on the type of the metal ion. The use of BHQ
      as an indicator via a spectrophotometric titration of Cu(II) and Ni(II) with EDTA
      was efficient.

PMID- 19767235
TI  - A quantitative analysis of the impact of a computerised information system on
      nurses' clinical practice using a realistic evaluation framework.
AB  - OBJECTIVE: To explore nurses' perceptions of the impact on clinical practice of
      the use of a computerised hospital information system. DESIGN: A realistic
      evaluation design based on Pawson and Tilley's work has been used across all the
      phases of the study. This is a theory-driven approach and focuses evaluation on
      the study of what works, for whom and in what circumstances. These relationships
      are constructed as context-mechanisms-outcomes (CMO) configurations.
      MEASUREMENTS: A questionnaire was distributed to all nurses working in in-patient
      units of a university hospital in Spain (n=227). Quantitative data were analysed
      using SPSS 13.0. Descriptive statistics were used for an overall overview of
      nurses' perception. Inferential analysis, including both bivariate and
      multivariate methods (path analysis), was used for cross-tabulation of variables
      searching for CMO relationships. RESULTS: Nurses (n=179) participated in the
      study (78.8% response rate). Overall satisfaction with the IT system was
      positive. Comparisons with context variables show how nursing units' context had
      greater influence on perceptions than users' characteristics. Path analysis
      illustrated that the influence of unit context variables are on outcomes and not
      on mechanisms. CONCLUSION: Results from the study looking at subtle variations in
      users and units provide insight into how important professional culture and
      working practices could be in IT (information technology) implementation. The
      socio-technical approach on IT systems evaluation suggested in the recent
      literature appears to be an adequate theoretical underpinning for IT evaluation
      research. Realistic evaluation has proven to be an adequate method for IT
      evaluation.

PMID- 19767236
TI  - Reduction of the postexcitatory cortical inhibition upon paired-click auditory
      stimulation in patients with Parkinson's disease.
AB  - OBJECTIVES: The aims of this study were: to investigate the postexcitatory
      inhibition of cortical evoked potentials on auditory paired-click stimulation in
      patients with Parkinson's disease (PD), to analyze the correlation of N1-P2
      amplitude ratios (A2/A1) with latency of the P300 auditory event-related
      potential and to determine the influence of Levodopa intake on postexcitatory
      inhibition and P300 latency. METHODS: The central (Cz) auditory evoked potentials
      were recorded in 61 patients with PD and 21 age-matched healthy subjects.
      RESULTS: Postexcitatory inhibition in auditory cortex in PD was significantly
      reduced for interstimulus intervals 500, 700 and 900ms compared to control group.
      The degree of this reduction correlated positively with the potential P300
      latency and negatively with the summary score of the Mini Mental State
      Examination (MMSE) which was used to study general cognitive status of the PD
      patients. Increase of the postexcitatory inhibition towards normal values and
      decrease of the P300 latency were observed (P<0.001) following the administration
      of Levodopa. CONCLUSIONS: The findings of this study testify that inhibitory
      processes in auditory cortex are deficient in PD patients. The positive effect of
      Levodopa administration indicates an important role of dopamine-dependent neural
      mechanisms in modulation of inhibitory processes in the auditory sensory system.
      SIGNIFICANCE: The results show that inability of the brain to provide normal
      inhibition in PD is accompanied by the decline of cognitive indices, including
      parameters of evoked potential P300 that is related to fundamental aspects of
      cognitive functions, such as attention and memory.

PMID- 19767237
TI  - Risk estimation for the next generation of prevention programmes for cervical
      cancer.

PMID- 19767238
TI  - Association of a dominantly inherited hyperphosphorylated paraprotein target with
      sporadic and familial multiple myeloma and monoclonal gammopathy of undetermined
      significance: a case-control study.
AB  - BACKGROUND: Chronic antigenic stimulation might have a role in the pathogenesis
      of monoclonal gammopathy of unknown significance (MGUS) and multiple myeloma. The
      aim of this study was to search for factors underlying the autoimmunogenicity of
      paratarg-7, a frequent antigenic target of paraproteins in MGUS and multiple
      myeloma. METHODS: Between January, 2005, and February, 2009, serum and peripheral
      blood cells were obtained from consecutive patients with MGUS or multiple myeloma
      and healthy blood donors, and paratarg-7 was analysed by DNA sequencing, SDS
      PAGE, isoelectric focusing, and western blotting. FINDINGS: Mutations or
      polymorphisms of paratarg-7 were not noted, but hyperphosphorylation was detected
      in 35 (13.9%) of 252 patients with MGUS or multiple myeloma, all of whom had an
      anti-paratarg-7-specific paraprotein. Analysis of eight families showed that
      hyperphosphorylated paratarg-7 is inherited in a dominant fashion, and that
      carriers of hyperphosphorylated paratarg-7 have an increased risk of developing
      MGUS and multiple myeloma (odds ratio [OR] 7.9, 95% CI 2.8-22.6; p=0.0001).
      INTERPRETATION: Familial MGUS and multiple myeloma were associated with a
      dominant inheritance of hyperphosphorylated paratarg-7, enabling family members
      at increased risk for MGUS or multiple myeloma to be identified. That only
      patients with MGUS or multiple myeloma who are carriers of hyperphosphorylated
      paratarg-7 had a paratarg-7-specific paraprotein suggests that the
      hyperphosphorylation of paratarg-7 induces auto-immunity and is involved in the
      pathogenesis of MGUS and multiple myeloma; for example, by chronic antigenic
      stimulation. FUNDING: Forderverein Krebsforschung Saar-Pfalz-Mosel e.V.
      (eingetragener Verein: officially registered charity) and HOMFOR (the research
      programme of the Saarland University Faculty of Medicine).

PMID- 19767239
TI  - Extended lymphadenectomy versus conventional surgery for rectal cancer: a meta
      analysis.
AB  - BACKGROUND: Lateral pelvic lymph-node metastases occur in 10-25% of patients with
      rectal cancer, and are associated with higher local recurrence and reduced
      survival rates. A meta-analysis was undertaken to assess the value of extended
      lateral pelvic lymphadenectomy in the operative management of rectal cancer.
      METHODS: We searched Medline, Embase, Ovid, Cochrane Library, and Google Scholar
      for studies published between 1965 and 2009 that compared extended
      lymphadenectomy (EL) with standard rectal resection. 20 studies, which included
      5502 patients from one randomised, three prospective non-randomised, and 14
      retrospective case-control studies published between 1984 and 2009, met our
      search criteria and were assessed. 2577 patients underwent EL and 2925 underwent
      non-EL for rectal cancer. Random and fixed-effects meta-analytical models were
      used where indicated, and between-study heterogeneity was assessed. End-points
      evaluated included peri-operative outcomes, 5-year survival and recurrence rates.
      FINDINGS: Operating time was significantly longer in the EL group by 76.7 min
      (95% CI 18.77-134.68; p=0.0096). Intra-operative blood loss was greater in the EL
      group by 536.5 mL (95% CI 353.7-719.2; p<0.0001). Peri-operative mortality (OR
      0.81, 95% CI 0.34-1.93; p=0.63) and morbidity (OR 1.45, 95% CI 0.89-2.35; p=0.13)
      were similar between the two groups. Data from individual studies showed that
      male sexual dysfunction and urinary dysfunction (three studies: OR 3.70, 95% CI
      1.66-8.23; p=0.0012) were more prevalent in the EL group. There were no
      significant differences in 5-year survival (hazard ratio [HR] 1.09, 95% CI 0.78
      1.50; p=0.62), 5-year disease-free survival (HR 1.23, 95% CI 0.75-2.03, p=0.41),
      and local (OR 0.83, 95% CI 0.61-1.13; p=0.23) or distant recurrence (OR 0.93, 95%
      CI 0.72-1.21; p=0.60). INTERPRETATION: Extended lymphadenectomy does not seem to
      confer a significant overall cancer-specific advantage, but does seem to be
      associated with increased urinary and sexual dysfunction.

PMID- 19767240
TI  - Risk of bleeding with vascular endothelial growth factor receptor tyrosine-kinase
      inhibitors sunitinib and sorafenib: a systematic review and meta-analysis of
      clinical trials.
AB  - BACKGROUND: Sunitinib and sorafenib are oral vascular endothelial growth factor
      receptor (VEGFR) tyrosine-kinase inhibitors used in various cancers. Bleeding has
      been described with these agents, although the overall risk remains unclear. We
      did a systematic review and meta-analysis to calculate the incidence and relative
      risk associated with use of sunitinib and sorafenib. METHODS: We searched PubMed
      (from January, 1966, to April, 2009) and meeting proceedings of the American
      Society of Clinical Oncology and the European Society of Medical Oncology (2004
      09) for relevant clinical trials. Eligible studies included phase 2 and 3 trials
      and expanded-access programmes. Statistical analyses were done to calculate
      summary incidences, relative risks, and 95% CI, using random-effects or fixed
      effects models based on the heterogeneity of included studies. FINDINGS: 23
      trials were selected for the meta-analysis, yielding a total of 6779 patients.
      The incidence of bleeding events (all grades) was 16.7% (95% CI 12.7-21.5), and
      that of high-grade events was 2.4% (1.6-3.9). The relative risk of all-grade
      bleeding events associated with sunitinib and sorafenib (for randomised
      controlled trials only) was 2.0 (1.14-3.49; p=0.015). Our analysis was also
      stratified by underlying malignant disease (renal-cell carcinoma vs non-renal
      cell carcinoma) and agent used, but no differences were recorded. INTERPRETATION:
      Treatment with the VEGFR tyrosine-kinase inhibitors sunitinib and sorafenib is
      associated with a significant increase in risk of bleeding. FUNDING: None.

PMID- 19767241
TI  - The role of Doppler and placental screening.
AB  - Placental-associated diseases account for most cases of adverse perinatal outcome
      in developing countries. Uterine Doppler evaluation predicts most instances of
      early-onset preeclampsia and intrauterine growth restriction, but there is no
      evidence in favour of any prophylactic strategy in cases of an abnormal screening
      result. Umbilical artery Doppler investigation allows identifying those small-for
      gestational-age foetuses at higher risk, and its use in these pregnancies
      improves a number of perinatal outcomes. Middle cerebral artery Doppler
      investigation reflects brain redistribution, and its use in combination with the
      umbilical artery in a cerebroplacental ratio seems to improve prediction of
      adverse outcome, mainly in near-term pregnancies, where most instances of adverse
      outcome occur in foetuses with normal umbilical artery. Ductus venosus Doppler
      waveform is a surrogate parameter of the foetal acid-base status. However, the
      benefits of its use in the management of early-onset growth restriction needs
      further evidence.

PMID- 19767242
TI  - Six months of postmarketing experience with adjunctive lacosamide in patients
      with pharmacoresistant focal epilepsy at a tertiary epilepsy center in Germany.
AB  - We report our 6 months of experience with adjunctive lacosamide in 25 patients
      with pharmacoresistant focal epilepsy. Baseline characteristics of our patients
      were similar to those of the populations in the three clinical trials that
      evaluated lacosamide for refractory focal epilepsy. One patient experienced
      sustained seizure freedom for 5 months; two more patients had nonsustained
      periods of seizure freedom of 1 and 4 months. A total of eight patients (32%)
      reported a greater than 50% reduction in seizure frequency. Thirteen patients
      (52%) reported side effects during the titration, mostly dizziness, fatigue,
      nausea, and gait instability. In five patients (20%), these disappeared during
      the maintenance phase and/or with dose reduction. Two patients lost more than 10%
      of their body weight. Otherwise, in terms of efficacy and adverse effects, our
      data mirror the profile of lacosamide described in the three clinical trials.
      Substantial weight loss may occur in individual patients.

PMID- 19767243
TI  - Longer duration of epilepsy and earlier age at epilepsy onset correlate with
      impaired cognitive development in infancy.
AB  - We assessed the impact of age at onset of epilepsy and duration and frequency of
      seizures on cognitive development in children less than 3 years old.
      Retrospective analysis was conducted on clinical data and neuropsychological
      testing of 33 infants with epilepsy. Developmental quotients were calculated and
      were correlated with age at epilepsy onset, duration of epilepsy, seizure
      frequency, brain pathology, and types of seizures (with/without spasms) as
      potential predictors. Infants with longer duration and earlier onset of epilepsy
      performed worse on developmental neuropsychological testing. Regression analyses
      showed that age at epilepsy onset and percentage of life with epilepsy were both
      strongly associated (regression model P<0.0001) with developmental quotient.
      There was no correlation with seizure frequency. Infants with spasms had worse
      developmental quotients than infants without spasms (P<0.001). These results
      suggest that duration of epilepsy and age at onset may be the best developmental
      predictors during the first years of life in patients with epilepsy. Early
      aggressive intervention should be considered.

PMID- 19767244
TI  - Refractory epilepsy in tuberous sclerosis: vagus nerve stimulation with or
      without subsequent resective surgery.
AB  - OBJECTIVE: The goal of the work described here was to assess the efficacy and
      safety of vagus nerve stimulation in a cohort of patients with tuberous sclerosis
      complex with refractory epilepsy. Furthermore, we examined the impact of vagus
      nerve stimulation failure on the ultimate outcome following subsequent
      intracranial epilepsy surgery. METHODS: A retrospective review was performed on
      19 patients with refractory epilepsy and TSC who underwent vagus nerve stimulator
      (VNS) implantation. There were 11 (58%) females and 8 (42%) males aged 2 to 44
      years when the VNS was implanted (mean: 14.7+/-12 years). Twelve patients
      underwent primary VNS implantation after having failed a mean of 7.1
      antiepileptic drugs. Two patients (17%) had generalized epilepsy, one had a
      single seizure focus, three (25%) had multifocal epilepsy, and six (50%) had
      multifocal and generalized epilepsy. Seven patients were referred for device
      removal and evaluation for intracranial procedures. One patient in the primary
      implantation group was lost to follow-up and excluded from outcome analysis.
      RESULTS: All implantations and removals were performed without permanent
      complications. The duration of treatment for primary VNS implants varied from 8.5
      months to 9.6 years (mean: 4.9 years). Mean seizure frequency significantly
      improved following VNS implantation (mean reduction: 72%, P<0.002). Two patients
      had Engel Class I (18%), one had Class II (9%), seven had Class III (64%), and
      one had Class IV (9%) outcome. Three patients with poor response to vagus nerve
      stimulation therapy at our center underwent resection of one or more seizure foci
      (Engel Class I, two patients; Engel Class III, one patient). Seven patients
      referred to our center for VNS removal and craniotomy underwent seizure focus
      resection (6) or corpus callosotomy (1) (Engel Class II: 2, Engel III: 2; Engel
      IV: 3). In total, 8 of 10 (80%) patients experienced improved seizure control
      following intracranial surgery (mean reduction: 65%, range: 0-100%, P<0.05).
      CONCLUSIONS: VNS is a safe and effective treatment option for medically
      refractory epilepsy in patients with tuberous sclerosis complex. Nine of 11
      patients (82%) experienced at least a 67% reduction in seizure burden. Lack of
      response to vagus nerve stimulation does not preclude subsequent improvement in
      seizure burden with intracranial epilepsy surgery.

PMID- 19767245
TI  - Laparoscopic conversion of adjustable gastric banding and vertical banded
      gastroplasty to duodenal switch.
AB  - BACKGROUND: The aim of this retrospective consecutive study was to evaluate the
      feasibility, safety, and efficacy of the conversion of laparoscopic adjustable
      gastric banding (LAGB) and open vertical banded gastroplasty (VBG) into duodenal
      switch (DS) by laparoscopy. METHODS: From November 2003 to February 2007,
      laparoscopic conversion into DS was performed in 1-step in 43 patients, 31 after
      LAGB and 12 after VBG. The reason for conversion was weight loss issues, such as
      insufficient excess weight loss (EWL) or weight regain. The mean interval from
      LAGB and VBG to conversion to the DS was 42.7 +/- 28.7 months and 172.2 +/- 86.9
      months, respectively. The mean %EWL at conversion was 8.3% +/- 19.3% after LAGB
      and 20.8% +/- 30% after VBG. RESULTS: The mean operative time was 205.8 +/- 44.8
      minutes for LAGB and 210.9 +/- 53.7 minutes for VBG. No conversions to open
      surgery occurred. One patient in the LAGB group died on the third postoperative
      day of sudden death syndrome, as shown by the postmortem examination. Major
      complications occurred in 6.4% of patients with LAGB (1 hemoperitoneum and 1
      ileoileostomy leak) and in 50% with VBG (1 sleeve gastrectomy leak with
      subsequent duodenoileostomy leak, 3 duodenoileostomy leaks, 1 pancreatitis, and 1
      respiratory insufficiency). The mean hospital stay was 5.5 +/- 5 days for the
      LAGB group and 34.5 +/- 50.3 days for the VBG group. After a mean follow-up of 28
      +/- 15.7 months for LAGB to DS and 43.5 +/- 6 months for VBG to DS, reoperations
      for late complications were required in 6 patients (20.6%) in the LAGB to DS
      group and in 5 patients (62.5%) in the VBG to DS group. Three patients (25%) died
      within 8 months after conversion of VBG. The 29 surviving patients (LAGB to DS)
      showed a mean %EWL and percentage of excess body mass index loss of (%EBMIL)
      78.4% +/- 24.9% and 77.8% +/- 23.7%, respectively. The 8 surviving patients (VBG
      to DS) had a mean %EWL and %EBMIL of 85.1% +/- 20% and 85.8% +/- 18.7%,
      respectively. CONCLUSION: According to these results, laparoscopic conversion of
      LAGB to DS seems feasible and effective, despite the 1 death. However, in our
      hands, laparoscopic conversion of VBG to DS had an unacceptable rate of
      complications and deaths.

PMID- 19767246
TI  - Relationship between exercise capacity and heart rate variability: supine and in
      response to an orthostatic stressor.
AB  - The study investigated whether supine-measured HRV indicators, and/or HRV
      indicators measured during orthostatic stress are related to conventional
      measures of exercise and performance ability such as VO(2max). Only two
      significant correlations (p<0.05) out of 30 tests were found between supine
      determined HRV indicators and conventional measures. In contrast, fifteen of the
      30 relationships calculated during orthostatic stress were significant.
      Relationships were at best low to moderate (0.2<|corr|<0.4). As expected, the
      relationships obtained during orthostatic stress were reversed from that obtained
      in the supine position. In summary, although HRV indicators are related to
      cardiovascular fitness, correlations between VO(2max) and these parameters are
      found only under very specific conditions. HRV parameters explain very little of
      the variance in VO(2max). In addition, estimating the exercise capacity from HRV
      indicators requires experience and extreme caution.

PMID- 19767247
TI  - Frequency of slow oscillations in arterial pressure and R-R intervals during
      muscle metaboreflex activation.
AB  - Altered frequency of slow (0.04-0.15Hz) arterial pressure and R-R interval
      oscillations has been observed in various diseases but the mechanisms for this
      frequency shift are unclear. The median (Med) frequencies of slow R-R interval
      and blood pressure (BP) oscillations were recorded in 11 healthy subjects with
      paced breathing (0.25Hz) during muscle metaboreflex and baroreflex mediated
      sympathetic stimuli: 1) handgrip exercise (HG) followed by post-exercise
      circulatory occlusion (PECO), 2) handgrip exercise during ischemia by circulatory
      occlusion (IHG) and 3) passive head-up tilt (TILT). Med(BP) shifted to the higher
      frequency during HG, PECO and IHG (from 0.070+/-0.009Hz to 0.088+/-0.013, 0.085+/
      0.015 and 0.099+/-0.013Hz, respectively, p<0.01 for all) but not during TILT
      (0.078+/-0.012Hz). Similarly, Med(R-R) shifted to the higher frequency during HG,
      PECO and IHG (from 0.072+/-0.009Hz to 0.085+/-0.014, 0.085+/-0.016 and 0.095+/
      0.015Hz, respectively, p<0.01 for all) but not during TILT (0.075+/-0.012Hz).
      Med(BP) and Med(R-R) were higher during IHG compared to HG and lower during TILT
      compared to both HG and IHG (p<0.01 for all). We conclude that the sympathetic
      stimulus induced by muscle metaboreflex is an important mechanism increasing the
      frequency of slow oscillations in arterial pressure and R-R intervals. The
      present results give new insight to understand the physiology underlying the
      frequency of slow arterial pressure and R-R interval oscillations.

PMID- 19767248
TI  - Nicotine stimulation of the medulla increases blood flow of the common carotid
      artery in cats.
AB  - Microinjection of nicotine or glutamate into the dorsal facial area (DFA) of the
      medulla increases blood flow of common carotid artery (CCA). Whether there is a
      causal relationship between these two events is not known. Various agonists and
      antagonists for the nicotinic and glutamatergic receptors were microinjected
      through a four-barrel tubing into the DFA of anesthetized cats. Microinjections
      of nicotine [a non-selective nicotinic acetylcholine receptor (nAChR) agonist],
      choline (a selective alpha7-nAChR agonist), glutamate or KCl induced a modest
      increase in CCA blood flow. The nicotine- and choline-induced increases were
      reduced by alpha-bungarotoxin (an alpha7-nAChR antagonist) as well as MK-801 (a
      non-competitive NMDA receptor antagonist) or glutamate diethylester (a
      competitive AMPA/kainate receptor antagonist). The glutamate or KCl-induced
      increases were blocked by MK-801 and glutamate diethylester, but not by alpha
      bungarotoxin. In conclusion, activation of nAChRs primarily via alpha7-nAChR
      caused a release of glutamate, which in turn activated NMDA and AMPA receptors,
      while cholinergic substance was not released into the DFA to activate the
      nicotinic receptor.

PMID- 19767249
TI  - In vivo direct monitoring of interstitial norepinephrine levels at the sinoatrial
      node.
AB  - We assessed in vivo interstitial norepinephrine (NE) levels at the sinoatrial
      node in rabbits, using microdialysis technique. A dialysis probe was implanted
      adjacent to the sinoatrial node of an anesthetized rabbit and dialysate was
      sampled during sympathetic nerve stimulation. Atrial dialysate NE concentration
      correlated well with heart rate. Desipramine significantly increased dialysate NE
      concentrations both before and during sympathetic nerve stimulation compared with
      the absence of desipramine. However, desipramine did not affect the relation
      between heart rate and dialysate NE concentration. These results suggest that
      atrial dialysate NE level reflects the relative change of NE concentration in the
      synaptic cleft. Microdialysis is a powerful tool to assess in vivo interstitial
      NE levels at the sinoatrial node.

PMID- 19767250
TI  - Impedance spectroscopy of human erythrocyte membrane: effect of frequency at the
      spectrin denaturation transition temperature.
AB  - Thermal analysis of suspension impedance was applied at various frequencies, f,
      to study the changes in erythrocyte membranes (EM) over the temperature interval
      47-53 degrees C where spectrin denatures. At f<crossover frequency (cof1) a
      decrease in EM resistance at 49.5 degrees C (A peak) has been observed. At
      f>cof1, when the capacitive conductance of EM becomes dominant, a second peak
      appeared at 50.5 degrees C (anti-A peak). The amplitudes of A and anti-A peaks
      reversibly depended on the phosphorylation of EM proteins. In contrast to the A
      peak, the anti-A peak was totally eliminated by modifications of EM with reagents
      that reduce EM deformability, O(s)O(4) (0.4-1mM) and putrescine (cytosolic
      concentration 1.5-2.0mM).

PMID- 19767251
TI  - Validation and application of a liquid chromatography-tandem mass spectrometric
      method for the simultaneous determination of testosterone and dihydrotestosterone
      in rat prostatic tissue using a 96-well format.
AB  - A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed
      to extract and quantify the androgen concentration in the rat prostate. This
      method introduced a novel 96-well plate format for the extraction and
      derivatization of testosterone (T) and dihydrotestosterone (DHT) from rat
      prostatic tissue that greatly simplified the sample preparation procedure. Due to
      the difficulty to obtain reproducible specimens with non-detectable level of
      androgen, a matrix-free standard solution was used for method validation. Both T
      and DHT calibration curves were linear over the calibration range (12.5-2500 pg)
      with correlation coefficient values greater than 0.9900. The intra-day and inter
      day accuracy, reported as %bias, and precision, reported as %CV, of T and DHT
      were within +/-10%. The lower limit of detection (LLOD) and lower limits of
      quantification (LLOQ) for both T and DHT were determined to be 5 and 12.5 pg. The
      validation results demonstrated the selectivity, sensitivity, accuracy,
      precision, linearity and ruggedness of the method, as well as the suitability of
      the method for simultaneous detection of T and DHT in rat prostatic tissues. The
      validated method was successfully applied to determine the physiological T and
      DHT level in rat prostatic tissues. Similarly to the serum concentration profile
      pattern, T and DHT intraprostatic levels peaked 2 h after lights-on and decreased
      after lights-off with DHT level approximately 4-fold greater than T.

PMID- 19767252
TI  - Gas chromatographic and mass spectrometric characterization of the organic acids
      extracted from some preparations containing lyophilized royal jelly.
AB  - Thirty-five aliphatic acids were identified by gas chromatography-mass
      spectrometry from the ether extract of commercial preparations containing
      lyophilized royal jelly. The article presents linear-programmed retention indices
      on capillary columns with non-polar and low-polar stationary phases and mass
      spectra for identified compounds which were not characterized earlier by these
      parameters. Nine compounds are reported for the first time as royal jelly
      constituents.

PMID- 19767253
TI  - Long-term clinical outcomes of self-expanding metal stents for treatment of
      malignant gastroesophageal junction obstructions and prognostic factors for stent
      patency: effects of anticancer treatments.
AB  - BACKGROUND: Self-expanding metal stent has emerged as an effective treatment
      option for malignant gastroesophageal junction obstruction. However, data on the
      clinicopathologic factors associated with stent patency are still lacking. AIM:
      To investigate the long-term clinical outcomes and prognostic factors, including
      treatment modalities, affecting stent patency in patients with malignant
      gastroesophageal junction obstruction given self-expanding metal stent
      insertions. METHODS: A total 89 patients who underwent self-expanding metal stent
      insertion for malignant gastroesophageal junction obstruction were enrolled. We
      analysed technical and clinical success rates, complications, and prognostic
      factors affecting stent patency. RESULTS: Self-expanding metal stent insertion
      was successful in all patients and clinical improvement was achieved in 93.3%.
      Stent malfunction occurred in 32.9% of patients. The median overall survival time
      and stent patency time were 143 (95% CI: 99-187) and 190 days (95% CI: 108-272),
      respectively. In multivariate analysis, radiation therapy after stent placement
      significantly prolonged stent patency (OR: 0.221; 95% CI: 0.055-0.884; p=0.033).
      A higher migration rate was observed in those patients given chemotherapy after
      covered self-expanding metal stent placement (no anticancer treatment: 10.0%,
      chemotherapy: 42.9%, chemoradiation therapy: 9.1%, p=0.042). CONCLUSIONS: Self
      expanding metal stent is a feasible and effective treatment for malignant
      gastroesophageal junction obstruction. Radiation therapy after stent placement
      significantly prolongs overall stent patency and chemotherapy increases the
      migration rate of covered stents.

PMID- 19767254
TI  - Systemic sclerosis as a model of chronic rejection in facial composite tissue
      transplantation.
AB  - INTRODUCTION: Chronic rejection remains a potential significant long-term problem
      of facial allograft transplantation. Scleroderma parallels chronic rejection in
      terms of its immunological pathophysiology and its histopathological processes.
      Through the analysis of facial changes in scleroderma we demonstrate how chronic
      facial allograft rejection may present and progress. METHODS: 129 consecutive
      patients with a clinical diagnosis of scleroderma were recruited into the study.
      Static facial disease assessment was carried out through the analysis of digital
      photographs. Facial motion dysfunction was assessed using a modified House
      Brackmann Grading Scale and an established maximal static response assay.
      Psychological evaluation comprised the Derriford Appearance Scale short-form
      (DAS), the Noticeability and Worry score and the Hospital Anxiety and Depression
      Scale (HADS). RESULTS: Static disease severity as measured using an observer
      rated disfigurement scale revealed all grades of disease in the scleroderma
      cohort - from mild through to severe. Significant positive correlations were seen
      between observer rated disfigurement and DAS24, Noticeability and Worry scores.
      No significant relationship could be seen between the indices of facial motion
      impairment and psychological scores. CONCLUSIONS: Progressive facial
      deterioration seen over time in scleroderma provides a comprehensive spectrum of
      static and dynamic facial changes which may be encountered in chronic facial
      graft rejection. This study provides valuable insight into the potentially
      significant long-term sequelae of allogenic reconstructive transplantation.

PMID- 19767255
TI  - The novel bone holding technique using thread-tapper device.
AB  - There are several surgical methods and instruments for open-reduction internal
      fixation of facial bone fractures. We describe a technique whereby a tapper,
      supplied as part of absorbable fixation instrument systems, is used to manipulate
      and hold the fractured bone segments. Our facility has used this technique for
      several years, and we are of the opinion that this novel method is very useful
      for fragmented small-bone fixation. The described technique simplifies the
      operating technique by minimising problems associated with the holding of reduced
      fragments before fixation.

PMID- 19767256
TI  - Long bones giant cells tumors: treatment by curretage and cavity filling
      cementation.
AB  - OBJECTIVE: Giant cell tumors (GCT) of bone are benign tumors with local
      aggressiveness that most of the time occur around the metaphyseal area of long
      bones, often in contact with the articular cartilage. Their treatment remains
      controversial because of their high recurrence rate. The authors report a
      retrospective series of 30 cases treated using curettage followed by cementation.
      They suggest demonstrating the mechanical and functional benefit of this
      technique, its benefit controlling the risk of recurrence, and of osteoarthritis
      potential. MATERIAL AND METHODS: Between 1992 and 2005, 30 patients with GCT were
      treated using curettage and cementation. Twenty-six of these tumors were present
      around the knee: 14 at the distal femur and 12 at the proximal tibia.
      Preoperative radiological evaluation with standard X-rays showed that the tumor
      measured a mean 71x45mm, for a mean volume of 78cm(3). Seventy-three percent of
      these GCT were in direct contact with the articular cartilage and 40% extended to
      the soft tissues as seen on the CAT scan and/or MRI. All patients were treated
      with curettage and cementation, 16 additional internal fixation procedures were
      performed. The mean follow-up of this series was 6 years and 4 months. All
      patients continue to be monitored, with none lost to follow-up. RESULTS: In all
      our cases, nine recurrences (30%) were observed during the first 2 years. Six
      patients were treated with a new curettage and cementation procedure and three
      underwent a total knee arthroplasty. None of these lesions had recurred at the
      last follow-up. The MSTS score, reflecting the function of the operated limb was
      a mean 93.33% (28 + or - 2/30). Standard radiological assessment showed a thin
      scalable border on four patients and was normal for the all-total arthroplasty
      cases. Two cases of minor osteoarthritis progression were noted (one less than
      50% and a simple densification of subchondral bone), requiring no specific
      treatment. Three complications were noted: one leg deep venous thrombosis, one
      hematoma, and one deep infection without impacting the initial treatment outcome
      over the long term. DISCUSSION: The curettage and cementation technique is usual
      practice in GCT treatment. Simple and reproducible, this technique has a lower
      rate of complication than other treatment options such as cryotherapy. It
      produces a lower rate of recurrence with the dual benefit of excellent mechanical
      and functional qualities. Diagnosis of recurrence can be made earlier because of
      the thin scalable border at the bone-cement interface. This technique does not
      generally cause osteoarthritis, which was found in only two cases with no
      evidence of the cement having a direct effect. The 30% recurrence rate observed
      in this series shows that the benefit provided by the cement as an adjuvant
      preservative remains modest. CONCLUSION: The cement mechanical and cytotoxic
      properties as well as its innocuity and its ease of handling make curettage and
      cementation one of the top-ranking GCT treatment options. An even lower rate of
      recurrence may be obtained through development of additional adjuvant treatments
      such as calcitonin and bisphosphonates. LEVEL OF EVIDENCE: Level IV; Therapeutic
      study.

PMID- 19767257
TI  - Planned creation of vascular access saves medical expenses for incident dialysis
      patients.
AB  - Hospitalization to initiate hemodialysis (HD) through temporary catheterization
      and subsequent creation of permanent vascular access (VA) is costly. Therefore,
      we studied the influence of the timing of VA creation on medical expenses, length
      of stay (LOS) and 1-year primary patency rate in incident HD patients. We
      analyzed the medical expenses associated with hospitalization and LOS at VA
      creation in 486 incident HD patients at two hospitals in southern Taiwan.
      Patients with early VA creation, more than 1 month before HD initiation, were
      defined as the Planned group (n = 70); less than 1 month as the Delayed group (n
      = 48); and those with VA creation after the initiation of HD as the Urgent group
      (n = 368). The Urgent group had the highest inpatient medical expenses and LOS
      compared with the other two groups. Multiple regression analyses of inpatient
      medical expenses and LOS showed that the timing of VA creation, the type of VA,
      marital and employment status and the number of comorbidities were significant
      factors responsible for the differences between groups. Furthermore, higher
      inpatient medical expenses and longer LOS in the Urgent group were noted in the
      arteriovenous fistula and arteriovenous graft subgroups. Kaplan-Meier Survival
      analysis showed that the 1-year primary patency rate was highest in the Delayed
      group and lowest in the Planned group, while Cox regression analysis demonstrated
      that the type of VA, but not the timing of VA creation, was a significant risk
      factor for VA patency. Arteriovenous graft had a higher risk for occlusion than
      arteriovenous fistula. In conclusion, planned VA creation before the initiation
      of HD is associated with lower inpatient medical expenses and shorter LOS, which
      should be promoted for pre-end-stage renal disease care, but the care for VA
      should be further emphasized before the progression to end-stage renal disease,
      and the patency of the VA should be cautiously monitored.

PMID- 19767258
TI  - Behavior problems and subtypes of attention-deficit hyperactivity disorder with
      comorbidities.
AB  - This study investigated the relationship between Child Behavior Checklist (CBCL)
      symptoms and attention-deficit hyperactivity disorder (ADHD) subtypes
      [inattentive (ADHD-I) and combined (ADHD-C)] with or without comorbidities.
      Overall, 116 ADHD children were interviewed using the Mini-International
      Neuropsychiatric Interview to assess ADHD subtypes and comorbidities, and were
      then divided into four groups according to their subtypes and comorbidities. The
      CBCL was completed by the parents of the ADHD children. The association between
      behavioral symptom severity and groups was examined by comparing the CBCL scales
      of the four groups. The scores for the Aggressive Behavior (p = 0.014) and
      Anxiety/Depression scales (p = 0.033) were higher in patients with ADHD-I with
      comorbidities than with ADHD-I without comorbidities. In addition, the score for
      the Aggressive Behavior scale was higher in patients with ADHD-C without
      comorbidities than in patients with ADHD-I without comorbidities (p = 0.011). The
      scores for the six CBCL scales were all higher in patients with ADHD-C with
      comorbidities than in patients with ADHD-I without comorbidities. Our findings
      suggest a synergistic effect of the co-occurrence of comorbidities and the ADHD-C
      subtype on behavioral symptom severity. Physicians could use the CBCL scales to
      distinguish patients with more severe symptoms from patients with less severe
      symptoms.

PMID- 19767259
TI  - Hepatocellular carcinoma associated with liver abscess.
AB  - Hepatitis B and hepatitis C are highly prevalent in Taiwan. Chronic hepatitis
      patients are at high risk of progression to liver cirrhosis and hepatocellular
      carcinoma (HCC). However, HCC in association with liver abscess is very rare.
      Accordingly, this study analyzed the characteristics of HCC patients with liver
      abscess to improve the differential diagnosis of this condition. From January
      2005 to July 2007, the medical records of nine HCC patients (4 females, 5 males;
      mean age, 65.8 years) treated for abscess formation at Kaohsiung Medical
      University Hospital were retrospectively reviewed. Their clinical
      characteristics, images, management approaches and outcomes were analyzed. Fever
      and highly elevated alkaline phosphatase levels were noted in all patients. All
      aspirate cultures revealed Klebsiella pneumoniae. All of the cases of HCC were
      confirmed by cytology or pathology. The imaging studies, which included abdominal
      ultrasonography and computed tomography, revealed liver tumors in all patients.
      In some cases, lead-enhanced hypervascular areas were noted. The patients were
      treated with antibiotic therapy, transhepatic arterial chemoembolization, or
      surgery. The findings of this study indicate that focal liver inflammatory
      changes may mimic solid neoplasms. Differential diagnosis of HCC with abscess is
      extremely difficult and may require aspiration cytology or pathology.

PMID- 19767260
TI  - Oxygen uptake for cycling in relation to body composition: a pilot study.
AB  - The purpose of this study was to investigate the relationship between oxygen
      uptake (VO2) for cycle ergometry and body composition in untrained healthy young
      men. Fifty-six men underwent body composition measurements and ramp work rate
      tests at 60 revolutions/minute on a cycle ergometer. Cell mass (CM), fat mass
      (FM), lean body mass (LMB) and total body mass (TBM) were assessed by
      multifrequency and segmental bioelectric impedance analysis. Resting, unloaded,
      and peak VO2 were determined by a gas analyzer, and their relationships with CM,
      FM, LBM, and TBM were analyzed. Values of VO2/TBM were positively related to the
      increasing CM/TBM ratios (p < 0.05-0.01). However, VO2/CM did not change with
      anthropometric characteristics (p > 0.05). Resting, unloaded and peak VO2 were
      more strongly related to CM (p < 0.005-0.001) than to FM, LBM or TBM. Our
      findings revealed that FM, LBM and TBM least affected the relationship between
      VO2 and CM. These data suggest that CM actually provides the preferred frame of
      reference for estimating the VO2 for cycle ergometry at 60 revolutions/minute in
      untrained healthy young men.

PMID- 19767261
TI  - Reconstruction of a massive femoral bone defect using a double-barreled free
      vascularized fibular bone graft after wide resection of femoral chondrosarcoma.
AB  - Salvaging the limb after malignant bone tumor ablation is a tough challenge for a
      reconstructive surgeon confronting such extensive bone defects. A 40-year-old
      male without any underlying disease was incidentally diagnosed with a
      chondrosarcoma over his left femoral bone. An orthopedic surgeon did a wide
      resection of the malignant bone tumor, leaving a massive bone defect about 11.3
      cm in length. A double-barreled free vascularized fibular bone was designed to
      reconstruct the femoral bone defect. The maximal fibular bone graft harvested was
      19 cm long; after the osteotomy, one barrel was 11 cm and the other was 8 cm. An
      iliac crest cancellous bone graft was harvested to fill the residual space. The
      pathology report showed a grade 1 well-differentiated conventional
      chondrosarcoma, and further adjuvant therapy was not suggested. At a 3-year
      follow-up, plain radiography showed a good bony union of the graft, and the
      patient could easily tolerate daily activity. A vascularized double-barreled
      fibular graft is an ideal option for reconstructing a massive defect in weight
      bearing bone: it provides not only sufficient mechanical strength but also good
      union for early rehabilitation. We describe the long-term results after
      reconstruction and provide a literature review of long-bone chondrosarcoma.

PMID- 19767262
TI  - A giant scrotal cavernous hemangioma extending to the penis and perineum: a case
      report.
AB  - Cavernous hemangioma is a congenital, benign vascular tumor that occurs in the
      deep dermis and subcutaneous tissue. Scrotal hemangiomas are rare entities and
      are usually diagnosed in childhood. Adult scrotal hemangiomas are also extremely
      rare. They are infrequently encountered in adults because they are usually
      removed in childhood. Urologists often face difficulties in deciding surgery to
      treat a genital cavernous hemangioma. Here, we report a case of scrotal cavernous
      hemangioma that involved the entire penis and scrotum, and extended to the
      perineum in a 44-year-old man, and we review the literature.

PMID- 19767263
TI  - Extensive subcutaneous emphysema after extraction of a mandibular third molar: a
      case report.
AB  - Surgical emphysema is an uncommon but potentially serious complication of third
      molar removal and other oral procedures. The purpose of this case report is to
      remind dentists of the risk of surgical emphysema. Surgical emphysema developed
      in a 32-year-old female after removal of a mandibular third molar using a high
      speed dental hand-piece. Because of the extent of the swelling, the patient was
      admitted for observation. Because of progressive swelling, a submandibular
      surgical incision and drainage was performed, which led to rapid resolution. The
      diagnosis and differential diagnosis of surgical emphysema are discussed to draw
      dentists' attention to the management and prevention of this complication.

PMID- 19767264
TI  - Use of a Holmium laser to treat a forgotten double-J stent with whole stent
      encrustations: a case report.
AB  - Short-term placement of double-J (D-J) ureteral stents after endourologic
      procedures and some open urological surgery is common. It is rare for a patient
      to forget about the indwelling D-J ureteral stent, and the major complications
      associated with that include infection, stone encrustation and multifractured
      stent. We report a case of a forgotten D-J ureteral stent, which had been placed
      24 months previously during ureterorenoscopic lithotripsy, in a 62-year-old man
      who presented with flank soreness and recurrent urinary tract infection.
      Radiography of the kidney, ureter and bladder, and computed tomography
      demonstrated stone encrustation over the whole D-J stent. Cystolithotripsy and
      ureterorenoscopic lithotripsy with a Holmium laser were performed to remove the D
      J. We believe that this is the first case of successful removal of an intact,
      encrusted stent in one procedure by endoscopic manipulation.

PMID- 19767266
TI  - Epidemiological trends in attempted suicide in adolescents and young adults
      between 1996 and 2004.
AB  - BACKGROUND: Notwithstanding the epidemiological studies indicating an increased
      risk of attempted suicide among adolescents and young adults, there is a scarcity
      of international studies that examine long-term epidemiological trends in rates
      and characteristics of this vulnerable group. AIMS: This article describes the
      results of a 9-year monitoring study of suicide attempts in adolescents and young
      adults referred to the Accident and Emergency Department of the Gent University
      Hospital (Belgium). METHODS: Between January 1996 and December 2004, trends,
      sociodemographic, and methodrelated characteristics of suicide attempts were
      assessed by a psychiatrist on data sheets. RESULTS: Attempted suicide rates
      declined from 1996 to 2001 and then rose until 2004, but did not exceed previous
      rates. During the 9 years of monitoring, there was a preponderance of female
      suicide attempters, except for 1997. Rates of attempts and of fatal suicide were
      negatively correlated. Significantly more males than females deliberately injured
      themselves. Younger attempters, especially females, significantly more often
      poisoned themselves with analgesics. In nearly one in five attempts, alcohol was
      used in combination with other methods, and alcohol intake was more commonly
      observed in older suicide attempters. Nearly half of the adolescents were
      identified as repeaters. CONCLUSIONS: The results of this study warrant further
      monitoring of trends and characteristics of young suicide attempters.

PMID- 19767267
TI  - The perspectives of young adults on recovery from repeated suicide-related
      behavior.
AB  - BACKGROUND: This qualitative study sought to develop an understanding of how
      young adults between the ages of 18-25 years, who have a history of two or more
      suicide attempts, transition away from high-risk suicide-related behaviors. AIMS:
      To understand the transition to safer behaviors and to provide clinical
      suggestions for those who provide care to this population. METHODS: Sixteen young
      adults under the age of 25 years, who had completed at least one cycle of
      intervention for people with repeated suicide attempts, participated in this
      qualitative, grounded theory study. RESULTS: The young adults described a pathway
      that included three major elements: (a) "living to die", (b) ambivalence and
      tipping/turning points, and (c) a process of recovery that included small steps
      or phases (pockets of recovery) toward life. The journey was not always
      experienced as steady movement forward, and the potential for relapse either in
      the young people's behavior or their wish to engage in their relationship with
      death could ebb and flow. CONCLUSIONS: Clinicians need to be aware that the
      struggle to live is a process involving a fluid pathway moving between three key
      elements.

PMID- 19767268
TI  - Suicide prevention with adolescents: considering potential benefits and untoward
      effects of public service announcements.
AB  - BACKGROUND/AIMS: Suicide is one of the most serious public health challenges; yet
      determining optimal methods for preventing suicide in adolescents continues to be
      an elusive goal. The aim of this study was to investigate possible benefits and
      untoward effects of suicide-prevention public service announcements (PSAs) for
      adolescents. METHODS: Adolescent participants (N = 426; 56% female) were randomly
      assigned to one of three conditions: (a) a billboard simulation, (b) a 30-s TV ad
      simulation, and (c) a no-information condition. RESULTS: The results of this
      study suggest some benefits for the information conveyed by the TV ad (e.g., more
      knowledgeable about depression). Few benefits were noted for adolescents who were
      exposed to billboard simulation, and the results raised substantial concerns
      about possible untoward effects, particularly in adolescents who were exhibiting
      depressive or suicidal symptoms. Billboard viewers were less likely to favor help
      seeking attitudes, perceived PSAs as being less useful, and endorsed more
      maladaptive coping. CONCLUSIONS: More research is urgently needed so that well
      intended efforts to prevent suicide can more optimally serve the desired goals.

PMID- 19767269
TI  - Severity of attempted suicide as measured by the Pierce Suicidal Intent Scale.
AB  - BACKGROUND: Suicidal intent is an essential feature of suicidal behavior.
      Previous research has been controversial and the need for further evidence has
      been pointed out. AIMS: The aim of the present study was to characterize the
      severity of attempted suicide by extracting components of suicidal intent and
      analyzing levels of suicidal intent by gender, age, and variables indicating the
      severity of attempted suicide. METHODS: Data on suicide attempters (N = 469) were
      collected in Estonia using WHO SUPRE-MISS methodology. To measure suicidal
      intent, a revised version of the Pierce Suicidal Intent Scale (PSIS) was used.
      RESULTS: The level of suicidal intent was not gender-dependent, but rose with
      age. Males and females were also similar in terms of discrete components.
      Classified in age groups, their unequivocally expressed "wish to die" was
      similar, but equivocal communication (components termed "arrangements" and
      "circumstances") increased with age. Middle-aged groups scored higher for the
      "alcohol/drugs" component. Psychiatric diagnosis, method of attempting suicide,
      and duration of hospitalization were linked to suicidal intent, but danger to
      life as assessed by interviewers was not. CONCLUSIONS: In suicide-risk
      assessment, results from a Suicidal Intent Scale contribute to clinical
      observation and add valuable information about a suicidal person's real
      intention.

PMID- 19767270
TI  - Can sports events affect suicidal behavior? A review of the literature and
      implications for prevention.
AB  - BACKGROUND: Engagement in sports and physical activity, either actively as an
      athlete or in a passive way as a spectator, impacts interpersonal behavior and
      physical and mental health. AIMS: The study reviews literature on the
      relationship between sports spectatorship and suicidal behavior to ascertain
      whether sports spectatorship has an impact on suicidal behavior, either
      increasing the risk or being a protective factor. METHODS: The literature was
      searched via PubMed/MEDLINE and PsycINFO. Nine studies published between 1986 and
      2006 were identified. RESULTS: The reviewed studies focused on the impact of
      sports events on the societal level, and analyzed data regarding national or
      local suicide rates. Their results indicate that sports events can have an impact
      on suicide mortality and morbidity, but this relationship seems to be mediated by
      age, gender, marital status, and alcohol consumption, as well as the process and
      outcome of the game (e.g., victory vs. defeat of the favored team). CONCLUSIONS:
      There is some evidence that sports events can reduce the rates of suicide on the
      societal level; however, there is a lack of studies exploring how sports
      spectatorship might influence levels of suicide risk in individuals and how
      mediating variables might operate on the individual level.

PMID- 19767271
TI  - Measuring hopelessness and life orientation in Pakistani adolescents.
AB  - BACKGROUND: To gain information on the attitudes and life orientations of
      Pakistani adolescents, the present study aimed at measuring hopelessness and
      hopefulness in Pakistani adolescents. METHODS: The Beck Hopelessness Scale (BHS;
      Beck, Weissman, Lester, & Trexler, 1974) and the Life Orientation Test (LOT;
      Scheier & Carver, 1985; Scheier, Carver, & Bridges, 1994) were translated into
      Urdu and validated for use in Pakistan. Back translation with a committee
      approach was used to translate the scales. The translated versions were
      administered to 723 adolescents and young adults in Pakistan. RESULTS: For the
      Urdu-BHS, all item-total correlation coefficients were significant and yielded a
      single component. The principal component analysis on the Urdu-LOT yielded two
      components representing positively worded Optimism items and negatively worded
      Pessimism items. The BHS, as well as the two subscales of the LOT, were found to
      be predictive of suicide ideation. Gender comparisons showed that the two genders
      differed significantly on Hopelessness and the Optimism component of the Urdu
      LOT. CONCLUSIONS: The Urdu version of the BHS and the LOT are established for use
      with young Pakistanis, after translations, and reliability and validity analyses.
      The need for further empirical research is emphasized for understanding the
      concepts and antecedents of hopelessness, optimism, and pessimism in adolescents,
      generally and in Pakistani adolescents, specifically.

PMID- 19767275
TI  - Abstracts of the Fourth Annual Congress of Update in Cardiology and
      Cardiovascular Surgery. November 28-December 2, 2008. Antalya, Turkey.

PMID- 19767272
TI  - The attitudes of emergency staff toward attempted suicide patients: a comparative
      study before and after establishment of a psychiatric consultation service.
AB  - BACKGROUND: The staff in the emergency room of general hospitals are under heavy
      work pressure and seem to reveal negative attitudes toward suicide attempters.
      From earlier studies there is indirect evidence that the attitudes of staff who
      have the opportunity to consult a psychiatrist are less negative. AIMS: The study
      compare the attitudes of emergency room staff in a general hospital toward
      patients who had attempted suicide before and after establishment of a
      psychiatric consultation service. METHODS: Attitudes were measured on the
      Understanding Suicidal Patients (USP) Scale. A total of 100 participants returned
      the questionnaire. RESULTS: General understanding and willingness to nurse
      patients who attempted suicide did not increase. CONCLUSION: The results suggest
      that providing a psychiatric consultation service did not significantly affect
      attitudes among general hospital emergency room staff toward attempted suicide
      patients during its first year of operation, but in general, the emergency room
      staff was content with the opportunity for psychiatric consultation.

PMID- 19767276
TI  - Abstracts of the Fifth Annual Congress of Update in Cardiology and Cardiovascular
      Surgery. September 25-28, 2009. Antalya, Turkey.

PMID- 19767277
TI  - Idiopathic recurrent pericarditis: searching for Ariadne's thread.

PMID- 19767278
TI  - Brugada syndrome: update 2009.

PMID- 19767279
TI  - The decline in PCI complication rate: 2003-2006 versus 1999-2002.
AB  - INTRODUCTION: Technical improvements permit the performance of percutaneous
      coronary interventions (PCI) reliably and safely. However, adverse events during
      such procedures have still not been eliminated. The purpose of this study was to
      assess the current rates of complications from PCI, as well as any changes from
      1999 to 2006. METHODS: Prospectively collected Lenox Hill Hospital data were
      abstracted from the New York State PCI Report forms and a review of the Quality
      Improvement office database. The reported complications from 23,399 consecutive
      PCIs performed during an eight-year period (January 1999 to December 2006) were
      recorded. The one-month composite endpoint (CEP: death, myocardial infarction,
      stent thrombosis, stroke, or emergent cardiac surgery within one month of the
      PCI) and the one-month composite endpoint excluding stent thrombosis (CEPnoST)
      were evaluated. RESULTS: Complications occurred in 3.36% of PCIs. The following
      complication rates were found: one month death rate 0.6%, death in the
      catheterization suite 0.047%, stent thrombosis (one month) 0.53%, presumed stent
      thrombosis (one month) 0.82%, myocardial infarction (MI: either Q or non-Q wave)
      0.74%, emergent cardiac surgery 0.15%, stroke 0.29%, cardiac perforation 0.29%,
      retroperitoneal bleeding 0.18%, acute renal failure 0.28%, need for hemodialysis
      0.17%, CEP 1.8% and CEPnoST 1.58%. When the complication rates from the most
      recent period (2003-2006) were compared with those from the earlier period (1999
      2002), a statistically significant difference was found in total complications,
      CEP, CEPnoST, stroke, MI, and vascular complications. CONCLUSIONS: Current rates
      of PCI complications remain low. The overall PCI complication rate was lower
      during the last four years of the study.

PMID- 19767280
TI  - Prevalence and five-year incidence (2001-2006) of cardiovascular disease risk
      factors in a Greek sample: the ATTICA study.
AB  - INTRODUCTION: The purpose of this study was to evaluate changes in the prevalence
      of cardiovascular disease (CVD) risk factors in a population-based sample of
      Greek adults. METHODS: From May 2001 to December 2002, 1514 men and 1528 women
      (age >18 y), living in the Attica region of Greece, were enrolled in the ATTICA
      cohort study. In 2006, the 5-year follow up was performed (941 of the 3042
      participants, 31%, were lost to follow up). The prevalence of hypertension,
      hypercholesterolemia, diabetes, obesity, smoking and physical inactivity, was
      assessed in both examinations through established procedures. Development of CVD
      (coronary heart disease, acute coronary syndromes, stroke, or other CVD) during
      the followup period was defined according to the WHO-ICD-10 criteria. RESULTS:
      During 2001-2006 there were 88 male and 102 female cases with hypertension per
      1000 individuals, 237 male and 177 female cases with hypercholesterolemia per
      1000 individuals, 58 male and 53 female cases with diabetes per 1000 individuals.
      In addition, 304 per 1000 males and 294 per 1000 females who were physically
      active at baseline examination became sedentary during the follow-up period. The
      prevalence of obesity reduced in males by 0.7% (p=0.66), but increased in females
      by 2.4% (p=0.10). Regarding smoking, its prevalence in 2001 was 47.2% in males
      and 39.6% in females; however, 27.5% of males and 24.5% of females stopped
      smoking, while 21.7% of males and 24.7% of females started smoking during the
      study period. The 5-year incidence of CVD was 11.0% in men and 6.1% in women
      (p<0.001); the case fatality rate was 1.6%. CONCLUSIONS: The burden of CVD risk
      factors is increasing at alarming rates in the investigated population. Our data
      underline the need for immediate action from public health care professionals in
      order to control the upcoming epidemic.

PMID- 19767281
TI  - The role of myocardial perfusion imaging in the evaluation of patients undergoing
      percutaneous transluminal coronary angioplasty.
AB  - INTRODUCTION: We studied the value of myocardial perfusion imaging (MPI) for the
      evaluation of improvement in myocardial perfusion in patients with successful
      percutaneous transluminal coronary angioplasty (PTCA). METHODS: Sixty patients
      (10 women, 50 men) aged 54.18 +/- 11.71 years were analyzed. MPI was performed
      before PTCA, 6-10 days (16 cases), 1-3 months (21 cases), and then 3-6 months (23
      cases) after the procedure. In all patients repeated coronary angiography was
      done at least once after PTCA. Statistical analysis of the numbers of segments
      with various degrees of perfusion (normal, ischemia, fixed segment), before and
      after PTCA, was performed for three groups (6-10 days, 1-3 months and 3-6 months
      after PTCA) separately, using paired T and also ANOVA tests. A p-value <0.05 was
      considered to be statistically significant. RESULTS: Improvement, defined as a
      decrease in the number of ischemic or fixed segments, was observed in 13 of 16
      patients at 6-10 days after PTCA, in 18 of 21 cases 1-3 months after PTCA, and in
      20 of 23 patients 3-6 months after PTCA. The sensitivity and specificity of MPI
      calculated before PTCA and at the 3 subsequent time points, using angiography as
      the gold standard, were 80/81, 100/35, 90/100, and 76/100 percent, respectively.
      CONCLUSION: Our results confirm the necessity for an assessment of perfusion both
      before and shortly after angioplasty, since it provides the best documentation of
      the changes in myocardial perfusion.

PMID- 19767282
TI  - The role of oxidative stress in atherosclerosis.

PMID- 19767283
TI  - Depression and heart failure.

PMID- 19767284
TI  - Pulmonary stenosis with extremely high pressure gradient in a young adult.

PMID- 19767285
TI  - Management of Behcet disease with multiple complications.
AB  - We present the case of an 18-year-old male patient with Behcet's disease who
      presented with dyspnoea, fever and haemoptysis. A diagnosis of right ventricular
      thrombosis associated with endomyocardial fibrosis, a pulmonary artery aneurysm,
      and cerebral vein thrombosis was made. Considering the absence of haemodynamic
      compromise and the risk of recurrence after surgical treatment for cardiac
      thrombus, we preferred medical management, which consisted of immunosuppression
      and anticoagulation. During a follow-up period of 9 months we observed complete
      dissolution of the thrombus and dramatic improvement of the patient's clinical
      status.

PMID- 19767286
TI  - Stent thrombosis four and a half years after implantation of a sirolimus-eluting
      stent.
AB  - We report on a case of very late stent thrombosis, 51 months after implantation
      of a sirolimus-eluting stent and 15 months after clopidogrel discontinuation.
      This case underlines the possible need for long-term antiplatelet medication in
      patients receiving sirolimus-eluting stents.

PMID- 19767287
TI  - Bradycardia and severe hypotension caused by wild honey poisoning.
AB  - Wild honey is taken as an alternative medicine for the treatment of
      gastrointestinal diseases as well as for coronary artery disease. However, wild
      honey made from the nectar of some species of rhododendron may be poisonous. The
      cause of the poisoning is the toxin grayanotoxin. Grayanotoxin is a naturally
      occurring sodium channel toxin that causes life-threatening bradycardia,
      hypotension, and altered mental status. Complete heart blocks may occur in some
      patients. We present an interesting case of bradycardia and hypotension due to
      wild honey ingestion. The symptoms, mechanism, and management of wild honey
      poisoning are discussed.

PMID- 19767288
TI  - PCI in severely degenerated saphenous vein graft using a novel mesh-covered stent
      together with a conventional embolic protection system.
AB  - Although the protection with filter-based devices during percutaneous coronary
      intervention (PCI) in a saphenous vein graft (SVG) reduces major adverse cardiac
      events, a large number of patients undergoing SVG PCI still experience these
      events. New methods must be used in order to reduce this incidence. Novel local
      plaque-trapping stents have been developed and show promise in pilot human
      testing. We present 2 cases of patients with degenerated SVGs and a large amount
      of plaque volume, who underwent coronary angioplasty in our department.
      Considering the high risk of distal embolization, we used a standard distal
      embolic protection system and a recently developed mesh-covered stent. This
      combination approach has not yet been studied very well.

PMID- 19767289
TI  - Reversible posterior leukoencephalopathy syndrome and takotsubo cardiomyopathy:
      the role of echocardiographic monitoring in the ICU.
AB  - We report a case of a female patient with acute renal failure due to
      polyarteritis nodosa. Her clinical course was initially complicated by an unusual
      form of hypertensive encephalopathy called reversible posterior
      leukoencephalopathy syndrome (RPLS). Soon afterwards she developed cardiogenic
      shock; she was intubated and admitted to our ICU. Echocardiography and pertinent
      laboratory data were suggestive of takotsubo cardiomyopathy (TTC), a rare form of
      stress-induced, reversible cardiac dysfunction. We hypothesized that TTC was
      pathophysiologically linked to RPLS, presumably through an overstimulation of the
      sympathetic nervous system. Both RPLS and TTC turned out to be totally reversible
      conditions, and intensive echocardiographic monitoring was of great importance in
      order to optimize the hemodynamic support in our patient.

PMID- 19767290
TI  - Cardiovascular magnetic resonance in Greece: the future is in our hands.

PMID- 19767291
TI  - Aspirin in primary prevention.

PMID- 19767292
TI  - The future of echocardiography.

PMID- 19767293
TI  - The ubiquitin-proteasome pathway and endothelial (dys)function.
AB  - The ubiquitin-proteasome system (UPS) has been recognized as a key regulatory
      pathway in cardiovascular diseases. Although the role of this system in the
      pathogenesis of endothelial dysfunction remains largely unknown, available data
      suggest that proteasome activity is modified by mediators and processes--e.g.
      nitric oxide and oxidative stress--involved in the regulation of endothelial
      function. In addition, there is some evidence that the UPS itself modulates the
      activity of endothelial nitric oxide synthase, the key enzyme of vascular
      homeostasis, interacts with other vasoactive mediators involved in regulation of
      endothelial function, influences oxidative stress response in the vasculature,
      and thereby contributes to regulation of endothelial (dys)function. This review
      discusses the potential implications of the UPS in endothelial dysfunction.

PMID- 19767294
TI  - Kruppel-like factor 15 regulates BMPER in endothelial cells.
AB  - AIMS: Bone morphogenetic proteins (BMPs) are involved in embryonic and adult
      blood vessel formation in health and disease. Previous studies have shown that
      BMP endothelial cell precursor-derived regulator (BMPER) plays an important role
      in endothelial cell function and blood vessel formation. BMPER is a key regulator
      of BMP4 activity and a prerequisite for BMP pathway activation by BMP4 in
      endothelial cells. Here, we characterize the BMPER promoter and elucidate
      mechanisms of BMPER regulation. METHODS AND RESULTS: To investigate
      transcriptional mechanisms of BMPER expression, the murine BMPER promoter was
      cloned and characterized. A series of 5' deletions of the BMPER promoter revealed
      that the proximal promoter contains activating cis-elements. By overexpression or
      siRNA-based knockdown, we demonstrate that BMPER expression is activated by
      Kruppel-like factor (KLF) 15. As determined by gelshift analyses, KLF15 binds
      directly to a predicted KLF-binding element at -284 bp within the BMPER promoter.
      Co-expression experiments show that Sp1 acts as an antagonist for KLF15-induced
      promoter activation. Endothelin-1 was identified as a potent inhibitor of KLF15
      and BMPER expression in endothelial cells, suggesting that KLF15 is a transducer
      of endothelin-1 activity on BMPER expression. The selective ET(B) endothelin
      receptor antagonist BQ788 abolished the downregulation of BMPER expression by
      endothelin-1. CONCLUSION: Mechanistically, we found that KLF15 is a strong and
      direct activator of the BMPER expression. BMPER is downregulated by endothelin-1
      in a dose-dependent fashion and in parallel to KLF15. As KLF15 deficiency is
      accompanied by a vascular phenotype and BMPER is necessary for proper blood
      vessel formation, we suggest a chain of events in which the effects of endothelin
      1 on BMPER are mediated by KLF15.

PMID- 19767295
TI  - Impaired cone function and cone degeneration resulting from CNGB3 deficiency:
      down-regulation of CNGA3 biosynthesis as a potential mechanism.
AB  - The cone cyclic nucleotide-gated (CNG) channel is essential for central and color
      vision and visual acuity. This channel is composed of two structurally related
      subunits, CNGA3 and CNGB3; CNGA3 is the ion-conducting subunit, whereas CNGB3 is
      a modulatory subunit. Mutations in both subunits are associated with
      achromatopsia and progressive cone dystrophy, with mutations in CNGB3 alone
      accounting for 50% of all known cases of achromatopsia. However, the molecular
      mechanisms underlying cone diseases that result from CNGB3 deficiency are
      unknown. This study investigated the role of CNGB3 in cones, using CNGB3(-/-)
      mice. Cone dysfunction was apparent at the earliest time point examined (post
      natal day 30) in CNGB3(-/-) mice. When compared with wild-type (WT) controls:
      photopic electroretingraphic (ERG) responses were decreased by approximately 75%,
      whereas scotopic ERG responses were unchanged; visual acuity was decreased by
      approximately 20%, whereas contrast sensitivity was unchanged; cone density was
      reduced by approximately 40%; photoreceptor apoptosis was detected; and outer
      segment disorganization was observed in some cones. Notably, CNGA3 protein and
      mRNA levels were significantly decreased in CNGB3(-/-) mice; in contrast, mRNA
      levels of S-opsin, Gnat2 and Pde6c were unchanged, relative to WT mice. Hence, we
      show that loss of CNGB3 reduces biosynthesis of CNGA3 and impairs cone CNG
      channel function. We suggest that down-regulation of CNGA3 contributes to the
      pathogenic mechanism by which CNGB3 mutations lead to human cone disease.

PMID- 19767296
TI  - Predictors of health status in nondepressed and nondemented individuals with
      Parkinson's disease.
AB  - Recent studies have shown that self-perceived health status (HS) in Parkinson's
      disease (PD) is associated with motor, cognitive, or mood symptoms, with the
      greatest association typically occurring with mood. The purpose of this study was
      to determine if these associations are present in nondepressed and nondemented
      individuals with PD by using sensitive neuropsychological measures and
      statistically derived factors from mood and motor scales. The best predictors of
      poor HS in PD participants (N = 32) without dementia or depression were mood
      symptoms, specific to self-reported cognitive impairment and anxiety. Bivariate
      correlations between HS and number of correct categories on the Wisconsin Card
      Sorting Test and the gait-balance factor from the Unified Parkinson's Disease
      Rating Scale Part III were also significant or approached significance. These
      findings suggest that specific mood and cognitive symptoms continue to be
      important factors in HS in those individuals who lack clinical levels of
      depression or dementia.

PMID- 19767297
TI  - Is the n-back task a valid neuropsychological measure for assessing working
      memory?
AB  - The n-back is a putative working memory task frequently used in neuroimaging
      research; however, literature addressing n-back use in clinical
      neuropsychological evaluation is sparse. We examined convergent validity of the n
      back with an established measure of working memory, digit span backward. The
      relationship between n-back performance and scores on measures of processing
      speed was also examined, as was the ability of the n-back to detect potential
      between-groups differences in control and Parkinson's disease (PD) groups.
      Results revealed no correlation between n-back performance and digit span
      backward. N-back accuracy significantly correlated with a measure of processing
      speed (Trail Making Test Part A) at the 2-back load. Relative to controls, PD
      patients performed less accurately on the n-back and showed a trend toward slower
      reaction times, but did not differ on any of the neuropsychological measures.
      Results suggest the n-back is not a pure measure of working memory, but may be
      able to detect subtle differences in cognitive functioning between PD patients
      and controls.

PMID- 19767298
TI  - Course of cognitive decline in hematopoietic stem cell transplantation: a within
      subjects design.
AB  - This study examined the course of clinically significant cognitive change in
      hematopoietic stem cell transplant (HSCT), using a Reliable Change Index (RCI).
      Neuropsychological evaluations were administered to 117 patients before HSCT.
      Thirty-three received subsequent evaluations 6 and 28 weeks later. Of 117
      patients, 39% were classified as impaired before HSCT. Of the 33 receiving
      subsequent evaluations, 47% showed reliable decline at 6-weeks; of these, 33%
      showed reliable decline again at 28-weeks. Mood and QOL did not account for
      declines. Verbal learning, psychomotor speed, and executive function showed
      greatest vulnerability to pre-HSCT impairment, and verbal learning showed
      greatest likelihood of further, subsequent decline. In conclusion, a subgroup of
      patients showed cognitive impairment before HSCT, indicating that factors other
      than HSCT contributed to cognitive deficits. Another subgroup showed further
      decline after HSCT. This study demonstrated the utility of the RCI in describing
      cognitive change in HSCT patients.

PMID- 19767299
TI  - Understanding hydrogen-bond patterns in proteins using network motifs.
AB  - Protein structures can be viewed as networks of contacts (edges) between amino
      acid residues (nodes). Here we dissect proteins into sub-graphs consisting of six
      nodes and their corresponding edges, with an edge being either a backbone
      hydrogen bond (H-bond) or a covalent interaction. Six thousand three hundred and
      twenty-two such sub-graphs were found in a large non-redundant dataset of high
      resolution structures, from which 35 occur much more frequently than in a random
      model. Many of these significant sub-graphs (also called network motifs)
      correspond to sub-structures of alpha helices and beta-sheets, as expected.
      However, others correspond to more exotic sub-structures such as 3(10) helix,
      Schellman motif and motifs that were not defined previously. This topological
      characterization of patterns is very useful for producing a detailed differences
      map to compare protein structures. Here we analyzed in details the differences
      between NMR, molecular dynamics (MD) simulations and X-ray structures for
      Lysozyme, SH3 and the lambda repressor. In these cases, the same structures
      solved by NMR and simulated by MD showed small but consistent differences in
      their motif composition from the crystal structures, despite a very small root
      mean square deviation (RMSD) between them. This may be due to differences in the
      pair-wise energy functions used and the dynamic nature of these proteins.
      AVAILABILITY: A web-based tool to calculate network motifs is available at
      http://bioinfo.weizmann.ac.il/protmot/.

PMID- 19767300
TI  - Client-side integration of life science literature resources.
AB  - MOTIVATION: The online resources in the life sciences are characterized by a
      great fragmentation and one of the pressing issues of bioinformatics is making
      the integration of these resources a smoother and more flexible process than it
      is currently. Here we present i-cite, a browser extension, which implements a
      client-side model of integration which improves the navigation within the rapidly
      increasing life science literature and links terms from it to corresponding non
      textual data. AVAILABILITY: http://i-cite.org.

PMID- 19767301
TI  - Can chronic neuropathic pain following thoracic surgery be predicted during the
      postoperative period?
AB  - Chronic pain following thoracic surgery is common and associated with neuropathic
      symptoms, however, the proportion of patients with neuropathic pain in the
      immediate postoperative period is unknown. We aimed to determine the proportion
      of patients who have neuropathic symptoms and signs immediately after, and at
      three months following thoracic surgery. The study was designed as a prospective
      observational cohort study. We identified patients with pain of predominantly
      neuropathic origin using the Leeds Assessment of Neuropathic Symptoms and Signs
      (LANSS) score in the immediate postoperative period and the self-report LANSS (S
      LANSS) version three months after surgery. One hundred patients undergoing video
      assisted thoracic surgery (VATS) or thoracotomy completed LANSS scores
      preoperatively and in the immediate postoperative period. Eighty-seven percent
      completed three months S-LANSS follow-up scores. Eight percent of patients had
      positive LANSS scores in the immediate postoperative period; 22% of patients had
      positive S-LANSS scores three months following surgery. There was a significant
      association between positive scores in the acute and chronic periods (relative
      risk (RR) 3.5, [95% confidence interval (CI) 1.7-7.2]). Identifying pain of
      predominantly neuropathic origin in the postoperative period with a simple pain
      score can help identify those at risk of developing chronic pain with these
      features following thoracic surgery.

PMID- 19767302
TI  - Endovascular treatment of thoracic aortic pathology in renal transplant
      recipients: early and intermediate-term results.
AB  - Endovascular correction of aorta thoracic pathology in renal transplant patients
      is a challenge. The aim of this study is to review early and intermediate-term
      results of endovascular repair of thoracic aorta pathology in patients with
      functioning previous renal transplant. The records of 81 patients submitted to a
      thoracic endograft between 2003 and 2008 were reviewed. Five patients with six
      previous renal transplants were submitted to six thoracic endografting. Two were
      women. The mean age was 55.4 years (range, 43-75 years). There were two patients
      with type B aortic dissection, one penetrating ulcer, one aneurysm of the aortic
      arch and one descending thoracic aorta aneurysm. Three patients underwent hybrid
      procedures: two total supra-aortic transpositions and one partial transposition
      of visceral trunks. Three patients presented postoperative complications. There
      were two cases of pneumonia, one acute limb ischemia and a stroke, with an early
      death. The mean follow-up was 16.2 months (range, 1-40 months). In this period
      all patients sustained renal function without any related complication. Despite
      the fact that it is a small series, in our clinical experience, endovascular
      thoracic aortic surgery can be performed as an alternative to open correction, in
      high-risk patients with a previous working renal transplant.

PMID- 19767303
TI  - Feasibility of ablation as an alternative to surgical metastasectomy in patients
      with unresectable sarcoma pulmonary metastases.
AB  - Percutaneous radiofrequency ablation (RFA) is an alternate treatment modality for
      pulmonary metastasis in non-surgical candidates. Four patients not suitable for
      surgery underwent percutaneous RFA for pulmonary metastases from leiomyosarcoma.
      Success of RFA was assessed with computed tomography (CT). The median length from
      the radiographic diagnosis of metastatic pulmonary disease (CT-scan) from the
      primary tumor diagnosis was 67.0 months with a range of 15.0-81.0 months. The
      median disease free interval following RFA was 19.0 months with a range of 4.0
      35.0 months. Three of four patients underwent the procedure uneventfully. RFA is
      a safe and minimally invasive intervention in non-surgical candidates with
      sarcoma pulmonary metastases.

PMID- 19767304
TI  - An observational study of CoSeal for the prevention of adhesions in pediatric
      cardiac surgery.
AB  - We sought to evaluate the utility and safety of CoSeal Surgical Sealant (Baxter)
      for the prevention of cardiac adhesions in children. Seven cardiac surgery
      centers in Europe recruited consecutive pediatric patients requiring primary
      sternotomy for staged repair of congenital heart defects. Exclusion criteria
      included immune system disorder, unplanned reoperation, or reoperation within
      three months of primary repair. CoSeal was sprayed onto the surface of the heart
      at the end of surgery. Evaluation of adhesions took place at first reoperation.
      Data on safety, duration of surgery, and ease of CoSeal use were also collected.
      Seventy-nine pediatric patients were recruited between February 2005 and
      September 2007. Of these, 76 underwent major surgery to repair a wide range of
      congenital heart defects. Thirty-six patients underwent reoperation >3 months
      after primary repair, and were included in the efficacy analysis. Mean adhesions
      score was 8.3 (standard deviation [S.D.] 2.4; range 7-16). Six adverse events (5
      serious) were possibly/definitely attributed to CoSeal. CoSeal's ease of use at
      primary operation was graded by surgeons as 12.1 mm (S.D. 9.8) on a visual analog
      scale of 0 ('very easy') to 100 mm ('very difficult'). Results of this
      prospective uncontrolled trial justify further investigation in a randomized,
      controlled trial.

PMID- 19767305
TI  - Functional characterization of B class MADS-box transcription factors in Gerbera
      hybrida.
AB  - According to the classical ABC model, B-function genes are involved in
      determining petal and stamen development. Most core eudicot species have B class
      genes belonging to three different lineages: the PI, euAP3, and TM6 lineages,
      although both Arabidopsis and Antirrhinum appear to have lost their TM6-like
      gene. Functional studies were performed for three gerbera (Gerbera hybrida) B
      class MADS-box genes--PI/GLO-like GGLO1, euAP3 class GDEF2, and TM6-like GDEF1-
      and data are shown for a second euAP3-like gene, GDEF3. In phylogenetic analysis,
      GDEF3 is a closely related paralogue of GDEF2, and apparently stems from a
      duplication common to all Asteraceae. Expression analysis and transgenic
      phenotypes confirm that GGLO1 and GDEF2 mediate the classical B-function since
      they determine petal and stamen identities. However, based on assays in yeast,
      three B class heterodimer combinations are possible in gerbera. In addition to
      the interaction of GGLO1 and GDEF2 proteins, GGLO1 also pairs with GDEF1 and
      GDEF3. This analysis of GDEF1 represents the first functional characterization of
      a TM6-like gene in a core eudicot species outside Solanaceae. Similarly to its
      relatives in petunia and tomato, the expression pattern and transgenic phenotypes
      indicate that GDEF1 is not involved in determination of petal identity, but has a
      redundant role in regulating stamen development.

PMID- 19767306
TI  - Phagotrophy in the origins of photosynthesis in eukaryotes and as a complementary
      mode of nutrition in phototrophs: relation to Darwin's insectivorous plants.
AB  - Darwin performed innovative observational and experimental work on the apparently
      paradoxical occurrence of carnivory in photosynthetic flowering plants. The
      nutritional use of particulate organic material which also supplies other
      elements is now known to be widespread in free-living algae as well as in
      organisms with endosymbiotic algae and with kleptoplastids. In addition to this
      direct nutritional role, phagotrophy, in the broad sense of internalization of
      photosynthetic organisms by a eukaryote, is essential for the occurrence of
      present-day endosymbiotic algae and kleptoplastid-containing protists, and was
      essential for the origin of plastids themselves. The endosymbiotic phenomena
      involving photosynthetic organisms clearly played a major role in combining
      genomes providing different metabolic functions, but, in our opinion, this does
      not demand a re-appraisal of evolution by natural selection. That the balance of
      physiological optimization for competition for resources and minimization of
      losses (e.g. through predation) is a fine one, and thus subject to a complex
      selective process, is illustrated by the diversity of mixotrophic strategies in
      extant phytoplankton.

PMID- 19767307
TI  - The expression of a chromoplast-specific lycopene beta cyclase gene is involved
      in the high production of saffron's apocarotenoid precursors.
AB  - Crocus sativus is a triploid sterile plant characterized by its long red stigmas,
      which produce and store significant quantities of carotenoid derivatives formed
      from the oxidative cleavage of beta-carotene and zeaxanthin. The present study
      reports on the genomic structures of two lycopene-beta-cyclase genes, CstLcyB1
      and CstLcyB2a, and on their transcription patterns in different C. sativus
      tissues. Phylogenetic analysis showed that both proteins are located in different
      groups: CstLcyB2a encodes chromoplast-specific lycopene cyclases, with an
      expression analysis showing strongly in flower stigmas where it activates and
      boosts beta-carotene accumulation. The CstLcyB1 transcript, however, was present
      in leaves, tepals, and stigmas at lower levels. In vivo assays in transgenic
      Arabidopsis demonstrated lycopene beta-cyclase activity of CstLcyB2a. CstLcyB2a
      is a CstLcyB1 paralogue derived through a gene duplication event, while promoter
      analysis showed that both genes have diverged in their regulatory sequences after
      duplication. Furthermore, it was found that the CstLcyB2a gene was absent from
      Crocus kotschyanus and, although present in C. goulimyi and C. cancellatus, the
      absence of transcripts suggests that transcriptional regulation of CstLcyB2a is
      responsible for the low apocarotenoid content in these species.

PMID- 19767308
TI  - Female reproductive success decreases with display size in monkshood, Aconitum
      kusnezoffii (Ranunculaceae).
AB  - BACKGROUND AND AIMS: Reduction in female fitness in large clones can occur as a
      result of increased geitonogamous self-fertilization and its influence through
      inbreeding depression. This possibility was investigated in the self-compatible,
      bee-pollinated perennial herb Aconitum kusnezoffii which varies in clone size.
      METHODS: Field investigations were conducted on pollinator behaviour, flowering
      phenology and variation in seed set. The effects of self-pollination following
      controlled self- and cross-pollination were also examined. Selfing rates of
      differently sized clones were assessed using allozyme markers. KEY RESULTS: High
      rates of geitonogamous pollination were associated with large display size.
      Female fitness at the ramet level decreased with clone size. Fruit and seed set
      under cross-pollination were significantly higher than those under self
      pollination. The pre-dispersal inbreeding depression was estimated as 0.502 based
      on the difference in seed set per flower between self- and cross-pollinated
      flowers. Selfing rates of differently sized clones did not differ. CONCLUSIONS:
      It is concluded that in A. kusnezoffii the negative effects of self-pollination
      causing reduced female fertility with clone size arise primarily from a strong
      early-acting inbreeding depression leading to the abortion of selfed embryos
      prior to seed maturation.

PMID- 19767309
TI  - Myco-heterotrophy: when fungi host plants.
AB  - BACKGROUND: Myco-heterotrophic plants are partly or entirely non-photosynthetic
      plants that obtain energy and nutrients from fungi. These plants form a symbiosis
      with arbuscular mycorrhizal, ectomycorrhizal or saprotrophic fungi to meet their
      nutrient demands. SCOPE: This Botanical Briefing summarizes current knowledge
      about myco-heterotrophy, discusses its controversial aspects and highlights
      future directions for research. CONCLUSIONS: Considerable recent progress has
      been made in terms of understanding the evolutionary history, germination and
      nutrition of myco-heterotrophic plants. Myco-heterotrophic plants: (1) are
      diverse and often ancient lineages that have coevolved with fungi, (2) often
      demonstrate unusually high specificity towards fungi during germination and
      maturity, and (3) can either cheat common mycorrhizal networks supported by
      neighbouring photosynthetic plants to satisfy all or part of their energetic and
      nutritional needs, or recruit free-living saprotrophic fungi into novel
      mycorrhizal symbioses. However, several fundamental aspects of myco-heterotrophy
      remain controversial or unknown, such as symbiotic costs and physiology.

PMID- 19767310
TI  - The neural basis of categorical face perception: graded representations of face
      gender in fusiform and orbitofrontal cortices.
AB  - Face gender, like many other things, is perceived categorically: Subjective
      perceptions are distorted toward the categories, male or female, and the
      objective gradiency inherent across faces is partially lost. The neural basis of
      such categorical face perception remains virtually unknown. Participants
      passively viewed faces whose sexually dimorphic content was morphed monotonically
      from male to female while neural activity was measured using functional magnetic
      resonance imaging. Subjective perceptions revealed strong nonlinearity despite
      monotonic linear changes in face gender, consistent with categorical perception.
      Neuroimaging results indicated that the lateral fusiform gyrus, bilaterally, and
      the fusiform face area linearly encoded graded parameters of objective face
      gender, but these regions correlated substantially less with subjective
      perceptions (which were nonlinear and affected by categorical perception
      effects). Such subjective perceptions, however, were represented in the
      orbitofrontal cortex, but this region correlated substantially less with
      objective parameters. The attention-independent graded representations of face
      gender in fusiform and orbitofrontal cortices reveal how objective face
      parameters are encoded and transformed into subjective categorically warped
      perceptions in the human brain.

PMID- 19767311
TI  - GABAergic differentiation induced by Mash1 is compromised by the bHLH proteins
      Neurogenin2, NeuroD1, and NeuroD2.
AB  - During forebrain development, Mash1 directs gamma-aminobutyric acid (GABA)ergic
      neuron differentiation ventrally in the ganglionic eminences. Repression of Mash1
      in the cortex is necessary to prevent the formation of GABAergic interneurons.
      Negative regulation of Mash1 has been attributed to members of the Neurogenin
      family; the genetic ablation of Neurogenin2 (Ngn2) leads to the derepression of
      Mash1 and the formation of ectopic GABAergic neurons in the cortex. We have
      developed an in vitro system to clarify the importance of NeuroD proteins in the
      Mash1 regulatory pathway. Using a neurosphere culture system, we show that the
      downstream effectors of the Ngn2 pathway NeuroD1 and NeuroD2 can abrogate
      GABAergic differentiation directed by Mash1. The ectopic expression of either of
      these genes in Mash1-expressing cells derived from the lateral ganglionic
      eminence, independently downregulate Mash1 expression without affecting
      expression of distal less homeodomain genes. This results in a complete loss of
      the GABAergic phenotype. Moreover, we demonstrate that ectopic expression of
      Mash1 in cortical progenitors is sufficient to phenocopy the loss of Ngn2 and
      strongly enhances ectopic GABAergic differentiation. Collectively, our results
      define the compensatory and cross-regulatory mechanisms that exist among basic
      helix-loop-helix transcription factors during neuronal fate specification.

PMID- 19767312
TI  - Comparison of four different display designs of a novel anaesthetic monitoring
      system, the 'integrated monitor of anaesthesia (IMA)'.
AB  - BACKGROUND: A novel monitoring system (integrated monitor of anaesthesia, IMA)
      which integrates three components of general anaesthesia on one single display
      was developed. The focus of this study was to evaluate the performance and user
      friendliness of four different display designs. METHODS: Four interface displays
      of the IMA were developed, including one numerical, one numerical and graphical
      (mixed numerical-graphical), one only graphical, and one an advanced two
      dimensional graphical display. Each of the four displays was evaluated in a
      random order by 10 staff anaesthetists and 10 residents/fellows using a set of
      five scenarios. Scenarios involved one or more abnormal variables that
      participants had to verbally phrase. For each interface test, reaction time,
      response accuracy, and NASA-Task Load Index were measured and compared. RESULTS:
      The numerical, graphical, and advanced-graphical interfaces yielded similar
      median reaction times, respectively, 7.99 s (5.15-10.79), 8.21 s (6.20-11.88),
      and 9.43 s (6.19-13.3). Reaction times were significantly shorter (P<0.006) with
      the mixed numerical-graphical interface: 6.26 s (4.52-8.32). The correct response
      rate was significantly lower in the graphical interface. The three others
      presented no statistical difference when compared among each other. The mixed
      numerical-graphical interface yielded a significantly lower NASA-TLX than the
      numerical and the advanced-graphical interfaces (19/100 vs 34/100, P<0.003).
      CONCLUSIONS: A mixed numerical-graphical display design appears to present the
      best results in terms of user reaction times, response accuracy, and performance
      index when detecting abnormal critical events.

PMID- 19767313
TI  - Deletion of mu-opioid receptor in mice does not affect the minimum alveolar
      concentration of volatile anaesthetics and nitrous oxide-induced analgesia.
AB  - BACKGROUND: The role of the endogenous opioid system in the anaesthetic effect of
      volatile anaesthetics and the analgesic action of nitrous oxide (N2O) is unclear.
      In the current study, we investigated whether the mu-opioid receptor (MOP) is
      involved in these activities using MOP knockout (MOP-KO) and wild-type (WT) mice.
      METHODS: Minimum alveolar concentrations (MACs) for sevoflurane, isoflurane, and
      halothane, and the sevoflurane MAC-sparing effect of N2O were determined in
      homozygous MOP-KO and WT mice. The analgesic effect of N2O and the suppressive
      effect of naloxone on N2O analgesia were assessed in a writhing test and a hot
      plate test. Immunohistochemical staining was used to visualize N2O-induced c-Fos
      expression in the lumbar spinal cord. RESULTS: There were no significant
      differences in the MAC values of the three volatile anaesthetics or in the
      sevoflurane MAC-sparing effect of N2O 70% between MOP-KO and WT mice. There was
      also no significant difference in the analgesic effect of N2O 70% or in the level
      of c-Fos expression induced by N2O 70% between the two genotypes. In the writhing
      test, naloxone significantly attenuated N2O analgesia in MOP-KO and WT mice.
      CONCLUSIONS: These results suggest that MOP is not required for the anaesthetic
      action of volatile anaesthetics and the analgesic effect of N2O. Opioid receptors
      other than MOP may mediate the analgesic action of N2O.

PMID- 19767314
TI  - Dose-dense temozolomide regimen for the treatment of brain metastases from
      melanoma, breast cancer, or lung cancer not amenable to surgery or radiosurgery:
      a multicenter phase II study.
AB  - BACKGROUND: Brain metastases reduce survival because therapeutic options are
      limited. This phase II study evaluated the efficacy of single-agent therapy with
      alternating weekly, dose-dense temozolomide in pretreated patients with brain
      metastases prospectively stratified by primary tumor type. METHODS: Eligible
      patients had bidimensionally measurable brain metastases from
      histologically/cytologically confirmed melanoma, breast cancer (BC), or non-small
      cell lung cancer (NSCLC). Prior chemotherapy, radiotherapy, and whole-brain
      radiotherapy (WBRT) were allowed. Patients received temozolomide 150 mg/m(2)/day
      (days 1-7 and 15-21 every 28- or 35-day cycle). RESULTS: In the intent-to-treat
      population (N = 157; 53 melanoma, 51 BC, and 53 NSCLC), one patient had complete
      response, nine (6%) had partial responses, and 31 (20%) had stable disease in the
      brain. Median progression-free survival was 56, 58, and 66 days for melanoma, BC,
      and NSCLC, respectively. Median overall survival was 100 days for melanoma, 172
      days for NSCLC, and not evaluable in the BC group. Thrombocytopenia was the most
      common adverse event causing dose modification or treatment discontinuation.
      Grade 4 toxic effects were rare. CONCLUSIONS: This alternating weekly, dose-dense
      temozolomide regimen was well tolerated and clinically active in heavily
      pretreated patients with brain metastases, particularly in patients with
      melanoma. Combining temozolomide with WBRT or other agents may improve clinical
      outcomes.

PMID- 19767315
TI  - Insulin-like growth factor receptor 1 (IGF1R) expression and survival in
      surgically resected non-small-cell lung cancer (NSCLC) patients.
AB  - BACKGROUND: The purpose of this study is to investigate the prognostic role of
      insulin-like growth factor receptor 1 (IGF1R) expression in surgically resected
      non-small-cell lung cancer (NSCLC). Patient characteristics and methods: This
      retrospective study was conducted in 369 stage I-II-IIIA, surgically resected,
      NSCLC patients. Patients exposed to anti-epidermal growth factor receptor (EGFR)
      agents were excluded. IGF1R expression was evaluated by immunohistochemistry in
      tissue microarray sections. RESULTS: A positive IGF1R expression (score > or =
      100) was observed in 282 cases (76.4%) and was significantly associated with
      squamous cell histology (P = 0.04) and with grade III differentiation (P = 0.02).
      No difference in survival was observed between the positive and negative group
      when score 100 was used as cut-off for discriminating a positive versus a
      negative IGF1R result (52 versus 48 months, P = 0.99) or when median value of
      IGF1R expression was used (45 versus 55 months, P = 0.36). No difference in
      survival was observed between IGF1R-positive and -negative patients in a subgroup
      of stage I-II adenocarcinoma (n = 137) with known EGFR mutation and copy number
      status. CONCLUSIONS: IGF1R expression does not represent a prognostic factor in
      resected NSCLC patients. Patients with squamous cell carcinoma overexpress IGF1R
      more frequently than patients with nonsquamous histology, justifying the
      different sensitivity to anti-IGF1R agents observed in clinical trials.

PMID- 19767316
TI  - Gender differences and cognitive aspects on functional outcome after hip fracture
      -a 2 years' follow-up of 2,134 patients.
AB  - BACKGROUND: hip fractures as well as cognitive dysfunction become increasingly
      prevalent in growing ageing populations. Hip fractures are approximately three
      times more common in elderly women. OBJECTIVE: we analysed outcome after hip
      fracture with respect to gender and cognitive function. DESIGN: population-based,
      prospective cohort study. SETTING: four university hospitals in Stockholm,
      Sweden. SUBJECTS: a total of 2,134 consecutive patients admitted with hip
      fracture during 2003. METHODS: gender differences in residence, walking ability
      and activity of daily living (ADL) were analysed at baseline, after 4 and 24
      months in patients with and without intact cognitive function. RESULTS: women
      were older, more often living alone and had poorer walking ability (P < 0.001).
      Cognitive dysfunction was equally common by gender. Women were more often treated
      with a prosthesis (P < 0.001) and sent to rehabilitation (P < 0.001). In the
      cognitive dysfunction group, men had more co-morbidity (P < 0.001) and total loss
      of walking ability (P = 0.03), but more often resided in own homes (P = 0.03).
      There was no gender difference in ADL. CONCLUSION: men had a higher risk for loss
      of walking ability and death only in patients with cognitive dysfunction.
      Cognitive function was the most important factor for returning to own home and
      regain pre-fracture function.

PMID- 19767317
TI  - The role of CDR H3 in antibody recognition of a synthetic analog of a
      lipopolysaccharide antigen.
AB  - In order to explore the structural basis for adaptability in near germline
      monoclonal antibodies (mAb), we have examined the specificity of the promiscuous
      mAb S67-27 to both naturally derived carbohydrate antigens and a variety of
      synthetic nonnatural antigens based on the bacterial lipopolysaccharide component
      3-deoxy-alpha-D-manno-oct-2-ulosonic acid (Kdo). One such analog, a 7-O-methyl (7
      O-Me) Kdo disaccharide, was found to bind to the antibody with at least 30-fold
      higher affinity than any other antigen tested. The structure of S67-27 in complex
      with this analog and three other naturally occurring Kdo antigens revealed that
      the enhanced affinity of the mAb for the synthetic analog was accomplished by the
      strategic positioning of CDR H3 away from a conserved Kdo binding pocket that
      allowed the formation of new antibody-antigen contacts. Furthermore, the
      comparison of this structure with the structures of related mAbs revealed how the
      position and structure of CDR H3 influence the specificity or promiscuity of near
      germline carbohydrate-recognizing antibodies by altering the architecture of the
      combining site.

PMID- 19767318
TI  - Efavirenz: a decade of clinical experience in the treatment of HIV.
AB  - Efavirenz, a non-nucleoside reverse transcriptase inhibitor, has been an
      important component of the treatment of HIV infection for 10 years and has
      contributed significantly to the evolution of highly active antiretroviral
      therapy (HAART). The efficacy of efavirenz has been established in numerous
      randomized trials and observational studies in HAART-naive patients, including
      those with advanced infection. In the ACTG A5142 study, efavirenz showed greater
      virological efficacy than the boosted protease inhibitor (PI), lopinavir.
      Efavirenz is more effective as a third agent than unboosted PIs or the nucleoside
      analogue abacavir. Some, but not all, studies have suggested that efavirenz
      (added to two nucleoside reverse transcriptase inhibitors) is more effective than
      nevirapine. Virological and immunological responses achieved with efavirenz-based
      HAART have been maintained for 7 years. Dosing convenience predicts adherence,
      and studies have demonstrated that patients can be switched from PI-based therapy
      to simplified, once-daily efavirenz-based regimens without losing virological
      control. The one-pill, once-daily formulation of efavirenz plus tenofovir and
      emtricitabine offers a particular advantage in this regard. Efavirenz also
      retains a role after failure of a first PI-based regimen. Efavirenz is generally
      well tolerated: rash and neuropsychiatric disturbances are the most notable
      adverse events. Neuropsychiatric disturbances generally develop early in
      treatment and they tend to resolve with continued administration, but they are
      persistent and troubling in a minority of patients. Efavirenz has less effect on
      plasma lipid profiles than some boosted PIs. Lipodystrophy can occur under
      treatment with efavirenz but it may be reduced if the concurrent use of thymidine
      analogues is avoided. Efavirenz resistance mutations (especially K103N) can be
      selected during long-term treatment, underscoring the importance of good
      adherence. Recent data have confirmed that efavirenz is a cost-effective option
      for first-line HAART. In light of these features, efavirenz retains a key role in
      HIV treatment strategies and is the first-line agent recommended in some
      guidelines.

PMID- 19767319
TI  - Screening for hepatitis C virus non-nucleotide resistance mutations in treatment
      naive women.
AB  - OBJECTIVES: Hepatitis C virus (HCV) non-nucleoside inhibitors (NNIs) target the
      viral RNA-dependent RNA polymerase encoded by the NS5B gene. Several NNIs share a
      similar allosteric binding site, and their antiviral efficacy is attenuated by a
      cysteine-to-tyrosine mutation at amino acid 316 (C316Y). In the current study, we
      assessed NS5B resistance mutations in treatment-naive individuals from a
      prospective natural history study of viral infections in women. METHODS: Partial
      NS5B sequences from HCV-positive women were amplified by RT-PCR. Additionally,
      subcloning was performed to evaluate intrapatient variability in selected
      samples. RESULTS: HCV NS5B genotypes were 45 genotype 1a (57.0%), 11 genotype 1b
      (13.9%), 5 genotype 2a (6.3%), 3 genotype 2b (3.8%), 9 genotype 3a (11.4%) and 6
      genotype 4a (7.6%). One HCV genotype 1a-infected patient was found to have the
      C316Y mutation (1.3%). Clonal analysis further revealed that all NS5B sequences
      from this individual--representing three serum samples collected 4 years apart-
      contained the C316Y mutation. In contrast, the S282T resistance mutation was not
      found in any samples. CONCLUSIONS: The C316Y polymerase resistance mutation was
      found in 1.3% of samples from HCV-infected women. The presence of this mutation
      over time suggests significant replicative fitness of this variant and has
      implications for development of new specifically targeted antiviral therapies
      against HCV (STAT-C) targeting this region.

PMID- 19767320
TI  - Denormalising smoking in the classroom: does it cause bullying?
AB  - BACKGROUND: The Smokefree Class Competition, the largest school-based smoking
      prevention programme in Europe, aims to create a class climate that denormalises
      smoking. An analysis was carried out to assess whether it increases bullying or
      perception of isolation. METHODS: A cluster randomised controlled trial was
      conducted, with two waves of assessment directly before the start and immediately
      after the end of the prevention programme. Some 3490 students were recruited from
      84 secondary schools in Germany, of whom 3123 students (90%) provided data from
      both waves. Classes from the intervention group (IG) participated in the
      Smokefree Class Competition, committing themselves to stay smokefree for a period
      of 6 months, and self-monitoring their smoking status on a weekly basis. Classes
      that refrained from smoking were eligible for a prize draw. To test the
      hypotheses that participation in the competition might foster bullying, we
      measured students' self report of (1) being victimised, (2) engaging in bullying
      and (3) being isolated. RESULTS: There was a strong association between daily
      smoking and higher odds of bullying others at baseline (adjusted proportional OR
      4.66; 95% CI 3.38 to 6.43). No significant pre-post differences across treatment
      assignment groups were found on any bullying measure using generalised linear
      latent and mixed models. For being isolated, the trends suggested that the
      programme, if anything, fostered lower levels of isolation at follow-up,
      especially for those who perceived high levels of isolation at baseline.
      CONCLUSION: Participation in the intervention had no effect on bullying or
      perceptions of isolation. TRIAL REG NO: ISRCTN27091233 in Current Control Trial
      Register.

PMID- 19767321
TI  - Louis-Rene Villerme (1782-1863), a pioneer in social epidemiology: re-analysis of
      his data on comparative mortality in Paris in the early 19th century.
AB  - BACKGROUND: During the early 19th century, contagionists' and anti-contagionists'
      explanations of disease causes opposed one another, and the Hippocratic miasma
      theory still predominated. According to that theory, geographic health
      disparities could be explained by topographical factors: differences in altitude,
      population density or proximity to a river. This article summarizes the life of
      Louis-Rene Villerme (1782-1863) and his major contributions to social
      epidemiology that proved the association between poverty and mortality. METHODS:
      In this study, data reported by Villerme to study the mortality-rate variations
      across the 12 districts (arrondissements) of Paris-that is, 1817-1826 Parisian
      death rates by district, population density and income indicators-are presented
      and reanalyzed. RESULTS: Results obtained with today's statistical techniques
      (correlation analysis) support Villerme's claims of a direct poverty-high death
      rate link: the three income indicators that he chose were significantly
      correlated with at-home mortality: taxation index (r=-0.83, p<0.002), average
      rent (r=-0.83, p<0.002), trade taxation index (r=-0.67, p<0.05), while population
      density variables were not associated with mortality. CONCLUSION: Villerme was
      not only a forerunner of social epidemiology, he was also a scientific pioneer by
      relying on data, not opinions, to challenge or support medical hypotheses.

PMID- 19767322
TI  - Randomised controlled trial of paper, online and SMS diaries for collecting
      sexual behaviour information from young people.
AB  - BACKGROUND: Diaries are used in sexual behaviour research to reduce recall bias.
      Diary collection via mobile phone text messaging (SMS) has not been trialled
      previously in sexual behaviour research. This randomised controlled trial
      compared SMS, paper and online diaries on response rate, timeliness, completeness
      of data and acceptability. The correlation between behaviour reported in all
      three types of diaries and data collected in a retrospective questionnaire was
      also determined. METHODS: Participants were recruited by telephone and randomised
      into one of three groups. They completed weekly sexual behaviour diaries for 3
      months by SMS, online or paper (by post). An online survey was conducted at the
      end of 3 months to compare retrospective reports to the diaries and assess
      opinions on the diary collection method. RESULTS: 72 participants were enrolled
      in the study, 24 in each group. Online diaries were more likely to be submitted
      late than SMS diaries (p<0.001). 3.9% of SMS diaries, 3.1% of paper diaries and
      0.5% of online diaries were incomplete (p=0.001). Online data collection was the
      preferred mode for 51%. 65 participants completed the end point retrospective
      questionnaire. The correlation between the diary and questionnaire on sexual risk
      classification was substantial (kappa=0.74) regardless of diary mode.
      CONCLUSIONS: SMS is a convenient and timely method of collecting brief
      behavioural data, but online data collection was preferable to most participants
      and more likely to be complete. Data collected in retrospective sexual behaviour
      questionnaires were found to agree substantially with data collected through
      weekly self-reported diaries.

PMID- 19767323
TI  - Comparision of two different ways of landfill gas utilization through greenhouse
      gas emission reductions analysis and financial analysis.
AB  - Greenhouse gas (GHG) emission reductions and utilization of landfill gas (LFG)
      were researched by comparing LFG displacing the use of natural gas (scenario 2)
      with electricity generation using LFG (scenario 3) at three different LFG
      collecting efficiencies; 35, 50 and 65%. The results show that the utilization of
      LFG in scenario 2 is 1.4 times that in scenario 3. GHG emission reductions
      generated by scenario 2 are slightly less than that of scenario 3. The GHG
      emission reductions and utilization of LFG are restricted by LFG collecting
      efficiencies. It will be helpful to improve the management level of landfill and
      the GHG emissions reduction by introducing the CDM. However, the utilization of
      LFG will be still short of financial attractiveness if the LFG collection
      efficiency is less than 50%.

PMID- 19767324
TI  - Recycling of metals: accounting of greenhouse gases and global warming
      contributions.
AB  - Greenhouse gas (GHG) emissions related to recycling of metals in post-consumer
      waste are assessed from a waste management perspective; here the material
      recovery facility (MRF), for the sorting of the recovered metal. The GHG
      accounting includes indirect upstream emissions, direct activities at the MRF as
      well as indirect downstream activities in terms of reprocessing of the metal
      scrap and savings in terms of avoided production of virgin metal. The global
      warming factor (GWF) shows that upstream activities and the MRF causes negligible
      GHG emissions (12.8 to 52.6 kg CO(2)-equivalents tonne(-1) recovered metal)
      compared to the reprocessing of the metal itself (360-1260 kg CO(2)-equivalents
      tonne(-1) of recovered aluminium and 400- 1020 kg CO(2)-equivalents tonne(- 1) of
      recovered steel).The reprocessing is however counterbalanced by large savings of
      avoided virgin production of steel and aluminium. The net downstream savings were
      found to be 5040-19 340 kg CO(2)-equivalents tonne(-1) of treated aluminium and
      560-2360 kg CO(2)-equivalents tonne(-1) of treated steel. Due to the huge
      differences in reported data it is hard to compare general data on the recovery
      of metal scrap as they are very dependent on the technology and data choices.
      Furthermore, the energy used in both the recovery process as well as the avoided
      primary production is crucial. The range of avoided impact shows that recovery of
      metals will always be beneficial over primary production, due to the high energy
      savings, and that the GHG emissions associated with the sorting of metals are
      negligible.

PMID- 19767325
TI  - Biomaterials from wool wastes: characterization of cortical cells/chitosan
      composite.
AB  - Anisotropic cortical cells were extracted from waste wool fibres by formic acid
      ultrasonic treatment and successively included in different proportions in a
      chitosan matrix to make film-forming composites, suitable for film casting and
      filament spinning. The morphological, chemical, thermal and mechanical properties
      of the composite film were investigated by scanning electron microscopy (SEM),
      light microscopy, X-ray diffraction (XRD), Fourier transform infrared (FT-IR)
      spectroscopy, differential scanning calorimetric (DSC) and tensile tests,
      respectively. The cortical cells/chitosan composite is capable of forming
      translucent composite films with acceptable mechanical and thermal properties.
      The chitosan composite film with addition of 30 wt.% cortical cells showed values
      of 29.6 +/- 2.9 MPa for ultimate strength, 5.6 +/- 0.3% for ultimate elongation
      and 35.3 +/- 1.4 MPa for Young's modulus, all higher than that of the pure
      chitosan film. DSC results revealed that the decomposition temperature of the
      composite film shifted to a higher temperature compared to the base materials, by
      increasing the mass fraction of cortical cells. XRD patterns showed that the
      crystallinity of biocomposite films increased with the addition of cortical
      cells. In addition, the FT-IR spectra of the composite film indicated that no
      chemical reaction occurs between cortical cells and chitosan; only a physical
      mixture of its constituents was present.

PMID- 19767326
TI  - Assessing the impacts of changes in treatment technology on energy and greenhouse
      gas balances for organic waste and wastewater treatment using historical data.
AB  - Historical data on organic waste and wastewater treatment during the period of
      1970-2020 were used to assess the impact of treatment on energy and greenhouse
      gas (GHG) balances. The assessment included the waste fractions: Sewage sludge,
      food waste, yard waste and other organic waste (paper, plastic, etc.). Data were
      collected from Aalborg, a municipality located in Northern Denmark. During the
      period from 1970-2005, Aalborg Municipality has changed its waste treatment
      strategy from landfilling of all wastes toward composting of yard waste and
      incineration with combined heat and power production from the remaining organic
      municipal waste. Wastewater treatment has changed from direct discharge of
      untreated wastewater to full organic matter and nutrient (N, P) removal combined
      with anaerobic digestion of the sludge for biogas production with power and heat
      generation. These changes in treatment technology have resulted in the waste and
      wastewater treatment systems in Aalborg progressing from being net consumers of
      energy and net emitters of GHG, to becoming net producers of energy and net
      savers of GHG emissions (due to substitution of fossil fuels elsewhere). If it is
      assumed that the organic waste quantity and composition is the same in 1970 and
      2005, the technology change over this time period has resulted in a progression
      from a net annual GHG emission of 200 kg CO( 2)-eq. capita(-1) in 1970 to a net
      saving of 170 kg CO(2)-eq. capita(-1) in 2005 for management of urban organic
      wastes.

PMID- 19767327
TI  - Development of protective coatings using fly ash premixed with metal powder on
      aluminium substrates.
AB  - Fly ash is a solid waste generated in huge quantities from coal-fired thermal
      power stations during the combustion of coal. Rich in metal oxides, it has
      tremendous potential as a coating material on structural and engineering
      components. This work aims at developing and characterizing a new class of such
      coatings made of fly ash by a novel technique - plasma spraying. Plasma spray
      technology has the advantage of being able to process various low-grade ore
      minerals to obtain value-added products and also to deposit ceramics, metals and
      a combination of these, generating near-homogeneous coatings with the desired
      microstructure on a range of substrates. In the present investigation, coatings
      are developed on aluminium substrates using fly ash premixed with aluminium
      powder in different weight proportions at various plasma torch input power levels
      ranging from 9- 18 kW DC. The coatings are characterized in terms of interface
      adhesion strength and deposition efficiency. Maximum adhesion strength of about
      35 MPa is recorded with coatings deposited at 12 kW power level. It was noticed
      that the quality and properties are significantly affected by the operating power
      level of the plasma sprayer. This work identifies fly ash as a potential coating
      material, suitable for possible tribological applications.

PMID- 19767328
TI  - Glycogen content is affected differently in acute pulmonary and extra-pulmonary
      lung injury.
AB  - Acute respiratory distress syndrome (ARDS) is the most severe form of acute lung
      injury (ALI). The aim of the present study was to investigate whether paraquat
      induced acute pulmonary and extra-pulmonary lung injury (ALI-P and ALI-EX,
      respectively), in rats, affects glycogen content in different tissues. This
      measurement could indicate performance limitations of tissues, a new biochemical
      aspect of ARDS. ALI-P and ALI-EX were induced by injection into the trachea (0.5
      mg/kg) and intraperitoneally (20 mg/kg) 24 hours prior to tissue collection. The
      control groups (CTRL) received the same volume of saline. Glycogen content (mg/g
      tissue) from different tissues was measured using the anthrone reagent. Glycogen
      content in the heart and kidney was higher in the ALI-EX group than the CTRL-EX
      group. Glycogen content in the gastrocnemius muscle was lower in the ALI-EX group
      than the CTRL-EX group. However, there were no significant differences in
      glycogen content in the diaphragm in the ALI-EX and ALI-P groups or in the
      gastrocnemius, heart and kidney in the ALI-P group when compared to the
      respective controls. ALI-EX caused a greater thickening of the alveolar walls,
      more areas of atelectasis and a greater abundance of inflammatory cells in
      comparison to ALI-P. These results demonstrate that glycogen content in ALI,
      induced by an herbicide that is highly toxic to humans and animals, is altered in
      different tissues depending on the location of the injury.

PMID- 19767329
TI  - The effects of subchronic lithium administration in male Wistar mice on some
      biochemical parameters.
AB  - Lithium salts are efficiently used for treatment of psychiatric disorders.
      However, prolonged treatment frequently involves adverse side effects. In this
      study, effects of lithium carbonate administration on some biochemical parameters
      were studied in male mice. Lithium carbonate (20, 40, or 80 mg/kg body weight
      corresponding to 3.77, 7.54, or 15.08 mg Li element/kg body weight, respectively)
      was injected daily for 14 or 28 days. The following parameters were recorded:
      drinking water consumption, body weight, lithium and testosterone serum
      concentrations, activities of catalase (CAT), superoxide-dismutase (SOD), and
      glutathione-peroxidase (GPX), and level of lipid peroxidation (expressed as
      TBARS) in liver was performed. Lithium treatment, especially at the highest dose
      for 28 days, was found to induce weight gain and polydipsia and a significant
      decrease of plasma testosterone level. Lipid peroxidation level and activities of
      SOD and GPX were increased in liver, which suggests a perturbation of the
      antioxidative status. Our results indicate that subchronic exposure to lithium,
      which induces weight gain and polydipsia under our experimental conditions, also
      damages the male reproductive system and triggers an oxidative stress in the
      liver.

PMID- 19767330
TI  - Persistent organic pollutants (POPs) in Africa: Egyptian scenario.
AB  - Persistent organic pollutants (POPs) are organic (carbon-based) compounds that
      include synthesized substances (pesticides and polychlorinated biphenyls [PCBs])
      and other by-product substances generated as a result of human and natural
      activity (dioxins and furans). Extensive scientific studies have shown that POPs
      are some of the most dangerous pollutants released into the environment by
      humans. Great efforts have been made since the early 1960s to enhance chemical
      management and safety issues. Various conventions have been adopted for this
      purpose: the Stockholm Convention (SC) is one of the well-known meetings in this
      context. The SC on POPs (May 2001) focuses on reducing and eliminating releases
      of 12 POPs coined the 'Dirty Dozen' by the United Nations Environment Program
      (UNEP). Persistence of such chemicals in soils, air, and water, together with
      natural processes such as evaporation to the atmosphere and washout by rain and
      flood, give rise to their ubiquitous distribution in the environment and eventual
      penetration into food chains and bio-accumulation in humans. Public concern about
      contamination by POPs increased recently because several of these compounds are
      identified as hormone disruptors, which can alter normal function of endocrine
      and reproductive systems in humans and wildlife. African countries are using
      pesticides, such as dichlorodiphenyltrichloroethane (DDT), lindane, toxaphene,
      endrin, dieldrin, heptachlor, since more than 50 years for combating agricultural
      pests and controlling disease vectors, especially malaria. The way in which
      pesticides are used in Africa caused serious environmental and health problems
      much more than elsewhere. These problems are represented by accumulation of
      organochlorine pesticide (OCP) residues in different environmental samples and
      hosting of at least 50,000 tons of obsolete pesticides, as well as tens of
      thousands of tons of contaminated soil. Within the framework of the Africa
      Stockpiles Program (ASP), huge quantities of pesticidal POPs have been completely
      or partially destroyed in a number of African countries (e.g. Egypt, Namibia,
      Niger, Senegal, Seychelles, South Africa, Sudan, Tanzania, Uganda, Zambia). At
      regional level (i.e. African Countries), a strategic plan for monitoring and
      getting rid of POPs in the continent should be set up and implemented through
      coordination between all governments. Among issues of top priorities are to find
      alternative non-combustion technologies for disposing obsolete pesticides, and to
      use alternative control measures for mosquitoes' management and other vector
      borne diseases.

PMID- 19767331
TI  - Risk factors for bleeding in pediatric post-cardiotomy patients requiring ECLS.
AB  - BACKGROUND/OBJECTIVE: There is limited literature documenting bleeding patterns
      in pediatric post-cardiotomy patients on extracorporeal life support (ECLS). This
      retrospective review details bleeding complications and identifies risk factors
      for bleeding in these patients. METHODS: Records from 145 patients were reviewed.
      Patients were divided into excessive (E) and non-excessive (NE) bleeding groups
      based on blood loss. RESULTS: Excessive bleeding occurred predominantly from 0
      6h. Longer CPB duration (NE=174+/-8 min; E=212+/-16; p=0.02) and lower platelet
      counts (NE=104.8+/-50K; E=84.3+/-41K; p=0.01) were associated with excessive
      bleeding during the first 6h (p=0.005). Use of intraoperative protamine with
      normal platelets was associated with decreased bleeding from 7-12 h post-ECLS
      (p=0.002). Most mediastinal exploration occurred > 49 h post-ECLS, with decreased
      bleeding post-exploration in E patients. CONCLUSIONS: The majority of pediatric
      post-cardiotomy ECLS bleeding occurs early after support initiation. Longer CPB
      time and thrombocytopenia increased bleeding 0-6h post-ECLS. Since early bleeding
      may be coagulopathic in origin, an approach to minimize bleeding includes
      protamine administration and aggressive blood product replacement with target
      platelet counts of 100-120K. Surgical exploration should follow if additional
      hemostasis is necessary.

PMID- 19767332
TI  - Analysis of the risk factors of postoperative respiratory dysfunction of type A
      aortic dissection and lung protection.
AB  - AIM: Retrospectively to analyze the risk factors of postoperative respiratory
      dysfunction (RD) in 196 patients with type A dissection operated on with cerebral
      perfusion and a lower body hypothermia circulatory arrest (HCA) and to
      investigate the method of the lung protection. METHODS: From January 2005 to
      April 2008, 196 patients with type A dissection underwent surgical repair with
      cerebral perfusion and HCA. There were 142 male patients and 54 female patients,
      with ages from 17 to 78 years. Antegrade selective cerebral perfusion (SCP)
      through the axillary artery was performed for 168 patients and retrograde
      cerebral perfusion (RCP) from the superior vena cava for 28 patients. All the
      factors underwent univariate and multivariate analysis. RESULTS: Mean
      cardiopulmonary bypass (CPB) duration was (186+/-56) minutes and mean cerebral
      perfusion time was (35+/-15) minutes; mean HCA time was (39+/-14) minutes.
      Postoperative RD was detected in 26 patients (13.3%). Multivariate analysis
      showed that the longer duration of circulatory arrest (CA), P=0.008, OR=1.048,
      and the higher temperature in the bladder during CA, P=0.002, OR=1.614, were
      independent risk factors of postoperative RD. There was a higher mortality
      (23.1%, P=0.025) in patients with postoperative RD when compared with the other
      patients. CONCLUSION: The longer duration of CA and the higher temperature in the
      bladder during CA were found to be the independent risk factors of postoperative
      RD after type A aortic dissection surgery. Attention should be paid to lung
      protection for these patients and the adjunct of continuing descending aortic
      perfusion and cerebral perfusion should be a safe and feasible procedure and it
      would be valuable to perform a prospective trial.

PMID- 19767333
TI  - Effect of Nd:YAG capsulotomy on the morphology of surviving Elschnig pearls.
AB  - AIM: To observe the short-term changes in morphology of Elschnig pearls induced
      by Nd:YAG capsulotomy. SETTING: Department of Ophthalmology, Medical University
      of Vienna, Austria METHOD: Twenty eyes of 19 pseudophakic patients with
      regeneratory posterior capsule opacification (PCO) that were scheduled for YAG
      capsulotomy were included in this prospective study. High-resolution digital
      retroillumination images were taken 2 weeks, 1 week and shortly before and
      immediately, 1 week and 2 weeks after Nd:YAG capsulotomy. The series of images
      were analysed using a dedicated image analysing software (PearlTracer). RESULTS:
      In total, 2431 Elschnig pearls were observed over the time-course of 4 weeks in
      this study. Of these, 535 pearls (30.6%) disappeared, and 503 pearls (27.6%)
      survived on the remaining capsule peripheral to the capsulotomy opening. The
      surviving pearls showed a significant decrease in size (20%) from immediately
      before to 10 min after capsulotomy. Within the first weeks after capsulotomy,
      there was a high number of newly appearing pearls, with 26% of all pearls being
      new between 1 and 2 weeks indicating high pearl turnover. CONCLUSION: Capsulotomy
      had an immediate impact on the morphology of PCO outside the capsulotomy opening,
      probably due to the direct mechanical impact of the laser shockwave.

PMID- 19767334
TI  - Research into Glaucoma and Ethnicity (ReGAE) 8: is there a relationship between
      social deprivation and acute primary angle closure?
AB  - OBJECTIVES: Social deprivation as measured by the Index of Multiple Deprivation
      (IMD) and Townsend scores has been shown to be associated with advanced
      presentation of primary open angle glaucoma. The aim of this study was to
      investigate the putative association of social deprivation as a risk factor for
      acute primary angle closure (APAC) in a UK urban population. METHODS: Case notes
      of 139 consecutive patients presenting with APAC at the Birmingham and Midland
      Eye Centre, Birmingham, UK, were examined. Deprivation was scored using the IMD
      2004 and Townsend scores. These score were compared with the West Midlands
      reference population. RESULTS: The level of deprivation in patients with APAC was
      graded according to the IMD quintiles, in which quintile 1 represents the highest
      level of deprivation and quintile 5 represents the lowest level of deprivation.
      Of the patients studied, 66.1% (n=90) were from quintiles 1 or 2 (most deprived)
      whereas 9% (n=12) came from quintile 5 (least deprived), compared with predicted
      frequencies of 40% and 20%, respectively. Deprivation levels measured by
      frequency within each IMD quintile were significantly higher in the APAC group
      compared with the reference population (chi(2), p<0.001). CONCLUSIONS: In this
      population patients presenting with APAC were more likely to come from areas with
      a high level of social deprivation.

PMID- 19767335
TI  - Face-down posturing after macular hole surgery: a meta-analysis.
AB  - AIMS To assess the effect that the duration of face-down posturing has on the
      outcome of macular hole surgery. METHODS A literature search was conducted to
      identify studies related to posturing duration following macular hole surgery.
      Where appropriate, studies were compared in a meta-analysis. The Mantel-Haenszel
      fixed-effect method was used to calculate the summary statistics. The main
      outcome measures were macular hole closure rate and visual acuity improvement.
      RESULTS 17 studies investigating the effect of face-down posturing time on the
      outcome of macular hole surgery were identified. 9 studies included a comparison
      group and were deemed suitable for inclusion in the meta-analysis. Studies were
      divided into two groups depending on the duration of face-down posturing
      investigated. The meta-analysis revealed an RR of anatomical failure of 1.34 (95%
      CI 0.66 to 2.72) with face-down posturing for 24 h or less compared with face
      down posturing for 5-10 days, but this was not statistically significant
      (p=0.42). The study design was too dissimilar to allow a meaningful comparison of
      visual acuity outcomes. CONCLUSIONS Currently there is insufficient evidence to
      allow firm conclusions as to whether face-down posturing following macular hole
      surgery influences hole closure rates. Meta-analyses are limited by the quality
      of included studies; a well-conducted randomised control trial is needed.

PMID- 19767336
TI  - Filtering Medline for a clinical discipline: diagnostic test assessment
      framework.
AB  - OBJECTIVE: To develop and test a Medline filter that allows clinicians to search
      for articles within a clinical discipline, rather than searching the entire
      Medline database. DESIGN: Diagnostic test assessment framework with development
      and validation phases. SETTING: Sample of 4657 articles published in 2006 from 40
      journals. Reviews Each article was manually reviewed, and 19.8% contained
      information relevant to the discipline of nephrology. The performance of 1 155
      087 unique renal filters was compared with the manual review. MAIN OUTCOME
      MEASURES: Sensitivity, specificity, precision, and accuracy of each filter.
      RESULTS: The best renal filters combined two to 14 terms or phrases and included
      the terms "kidney" with multiple endings (that is, truncation), "renal
      replacement therapy", "renal dialysis", "kidney function tests", "renal", "nephr"
      truncated, "glomerul" truncated, and "proteinuria". These filters achieved peak
      sensitivities of 97.8% and specificities of 98.5%. Performance of filters
      remained excellent in the validation phase. CONCLUSIONS: Medline can be filtered
      for the discipline of nephrology in a reliable manner. Storing these high
      performance renal filters in PubMed could help clinicians with their everyday
      searching. Filters can also be developed for other clinical disciplines by using
      similar methods.

PMID- 19767343
TI  - Flu's unexpected bonus.

PMID- 19767344
TI  - Heroin clinics reduce street drug use and crime, shows study.

PMID- 19767346
TI  - Chief medical officer warns that swine flu may be on the rise again.

PMID- 19767347
TI  - ZP domain proteins in the abalone egg coat include a paralog of VERL under
      positive selection that binds lysin and 18-kDa sperm proteins.
AB  - Identifying fertilization molecules is key to our understanding of reproductive
      biology, yet only a few examples of interacting sperm and egg proteins are known.
      One of the best characterized comes from the invertebrate archeogastropod abalone
      (Haliotis spp.), where sperm lysin mediates passage through the protective egg
      vitelline envelope (VE) by binding to the VE protein vitelline envelope receptor
      for lysin (VERL). Rapid adaptive divergence of abalone lysin and VERL are an
      example of positive selection on interacting fertilization proteins contributing
      to reproductive isolation. Previously, we characterized a subset of the abalone
      VE proteins that share a structural feature, the zona pellucida (ZP) domain,
      which is common to VERL and the egg envelopes of vertebrates. Here, we use
      additional expressed sequence tag sequencing and shotgun proteomics to
      characterize this family of proteins in the abalone egg VE. We expand 3-fold the
      number of known ZP domain proteins present within the VE (now 30 in total) and
      identify a paralog of VERL (vitelline envelope zona pellucida domain protein
      [VEZP] 14) that contains a putative lysin-binding motif. We find that, like VERL,
      the divergence of VEZP14 among abalone species is driven by positive selection on
      the lysin-binding motif alone and that these paralogous egg VE proteins bind a
      similar set of sperm proteins including a rapidly evolving 18-kDa paralog of
      lysin, which may mediate sperm-egg fusion. This work identifies an egg coat
      paralog of VERL under positive selection and the candidate sperm proteins with
      which it may interact during abalone fertilization.

PMID- 19767348
TI  - An ancient fission of mitochondrial Cox1.
AB  - Many genes inherited from the alpha-proteobacterial ancestor of mitochondria have
      undergone evolutionary transfer to the nuclear genome in eukaryotes. In some rare
      cases, genes have been functionally transferred in pieces, resulting in split
      proteins that presumably interact in trans within mitochondria, fulfilling the
      same role as the ancestral, intact protein. We describe a nucleus-encoded
      mitochondrial protein (here named Cox1-c) in the amoeboid protist Acanthamoeba
      castellanii that is homologous to the C-terminal portion of conventional
      mitochondrial Cox1, whereas the corresponding portion of the mitochondrion
      encoded A. castellanii Cox1 is absent. Bioinformatics searches retrieved nucleus
      encoded Cox1-c homologs in most major eukaryotic supergroups; in these cases,
      also, the mitochondrion-encoded Cox1 lacks the corresponding C-terminal motif.
      These data constitute the first report of functional relocation of a portion of
      cox1 to the nucleus. This transfer event was likely ancient, with the resulting
      nuclear cox1-c being differentially activated across the eukaryotic domain.

PMID- 19767349
TI  - Cognitive impairment in affective psychoses: a meta-analysis.
AB  - It has recently been suggested that cognitive impairment should be included in
      the diagnostic criteria of schizophrenia. One of the main arguments in support of
      this suggestion has been the hope that cognitive impairment can help distinguish
      schizophrenia from bipolar disorder (BD). However, recent evidence shows that
      cognitive deficits occur in BD and persist beyond euthymia. Further, mood
      disorders with psychotic features might be expected to manifest greater cognitive
      impairment, which further complicates the potential to differentiate these
      disorders. The goal of the current meta-analysis was to examine the magnitude and
      characteristics of cognitive impairments in affective psychoses (AP). A
      systematic search of the existing literature sourced 27 studies that met the
      inclusion criteria. These studies compared cognitive performances of 763 patients
      with AP (550 BD and 213 major depressive disorder) and 1823 healthy controls.
      Meta-regression and subgroup analyses were used to examine the effects of
      moderator variables. Meta-analyses of these studies showed that patients with AP
      were impaired in all 15 cognitive tasks with large effect sizes for most
      measures. There were no significant differences between the magnitude of
      impairments between the BD and major depressive disorder groups. The largest
      effect size was found for symbol coding, stroop task, verbal learning, and
      category fluency, reflecting impairments in elementary and complex aspects of
      attentional processing, as well as learning and memory. In general, the pattern
      of cognitive impairments in AP was similar to reported findings in euthymic
      patients with BD, but relatively more pronounced.

PMID- 19767351
TI  - Socioeconomic position and the tracking of physical activity and
      cardiorespiratory fitness from childhood to adulthood.
AB  - This study examined the influence of childhood socioeconomic position (SEP) and
      social mobility on activity and fitness tracking from childhood into adulthood.
      In a prospective cohort of 2,185 Australian adults (aged 26-36 years), first
      examined in 1985 (at ages 7-15 years), self-reported physical activity and
      cardiorespiratory fitness (subsample only) were measured. SEP measures included
      retrospectively reported parental education (baseline) and own education (follow
      up). There was little evidence of a relation between childhood SEP and activity
      tracking, but high childhood SEP (maternal education) was associated with a 59%
      increased likelihood of persistent fitness, and medium childhood SEP (paternal
      and parental education) was associated with a 33%-36% decreased likelihood of
      persistent fitness. Upward social mobility was associated with a greater
      likelihood of increasing activity (38%-49%) and fitness (90%), and persistently
      high SEP was associated with a greater likelihood of increasing activity (males:
      58%) and fitness (males and females combined: 89%). In conclusion, persistently
      high SEP and upward social mobility were associated with increases in activity
      and fitness from childhood to adulthood. Findings highlight socioeconomic
      differentials in activity and fitness patterns and suggest that improvements in
      education may represent a pathway through which physical activity levels can be
      increased and health benefits achieved.

PMID- 19767350
TI  - Invited commentary: Physical activity over the life course--whose behavior
      changes, when, and why?
AB  - Physical activity tends to decline from childhood into adulthood. Maintaining
      high levels of physical activity throughout life is therefore an important public
      health objective. Relatively little is known about changes in physical activity
      behavior over the life course, the domains of physical activity in which they
      occur, the characteristics of those whose physical activity declines, and the
      factors associated with such changes. In the future, incorporating more accurate
      measures of physical activity in large population studies would help to establish
      more accurate estimates of associations in this area. Determinants of behavior
      change, including the effects of socioeconomic position and social mobility on
      physical activity and fitness, are likely to change constantly throughout life,
      but it is largely unknown which determinants are most important at each life
      stage, let alone whether and at what times those determinants change. Better
      evidence on determinants of behavior change throughout the life course would
      contribute greatly to understanding when and how to intervene to help create and
      sustain lifelong healthy behavior patterns in those who have the most to gain
      from adopting them.

PMID- 19767353
TI  - Campylobacter volucris sp. nov., isolated from black-headed gulls (Larus
      ridibundus).
AB  - During a study of the prevalence of Campylobacter jejuni in black-headed gulls
      (Larus ridibundus) in Sweden, three isolates, strains LMG 24379, LMG 24380T and
      LMG 24381, were initially identified as Campylobacter lari. Further
      characterization by both AFLP and whole-cell protein SDS-PAGE analyses revealed
      that they formed a distinct group in the genus Campylobacter. This unique
      position was confirmed by phenotypic characterization, 16S rRNA and hsp60 gene
      sequence analysis and DNA-DNA hybridizations. The combined data confirm that
      these isolates represent a novel species within the genus Campylobacter, for
      which the name Campylobacter volucris sp. nov. is proposed. The type strain is
      LMG 24380T (=CCUG 57498T).

PMID- 19767354
TI  - Chryseobacterium solincola sp. nov., isolated from soil.
AB  - A Gram-staining-negative, yellow-pigmented, strictly aerobic bacterium,
      designated strain 1YB-R12T, was isolated from a soil sample in western Algeria.
      The novel isolate was heterotrophic, chemoorganotrophic, halotolerant and
      psychrotolerant. The temperature and pH optima for growth were 28-30 degrees C
      and pH 7.3-8. The bacterium tolerated up to 6% (w/v) NaCl. Cells were non-motile,
      non-gliding and non-spore-forming, and were characterized by a variable
      morphological cycle. Flexirubin-type pigments were not detected. 16S rRNA gene
      sequence analysis showed that strain 1YB-R12T occupied a distinct lineage within
      the genus Chryseobacterium and shared highest sequence similarity with
      Chryseobacterium haifense LMG 24029T (96.5%). The DNA G+C content of strain 1YB
      R12T was 40.9 mol%. The predominant cellular fatty acids were anteiso-C15:0
      (41.4%) and iso-C15:0 (14.4%). On the basis of phenotypic properties and
      phylogenetic distinctiveness, strain 1YB-R12T is considered to represent a novel
      species of the genus Chryseobacterium, for which the name Chryseobacterium
      solincola sp. nov. is proposed. The type strain is 1YB-R12T (=DSM 22468T=CCUG
      55604T).

PMID- 19767355
TI  - Bacteroides clarus sp. nov., Bacteroides fluxus sp. nov. and Bacteroides
      oleiciplenus sp. nov., isolated from human faeces.
AB  - Three Gram-stain-negative, obligately anaerobic, non-spore-forming, rod-shaped
      bacteria (strains YIT 12056T, YIT 12057T and YIT 12058T) were isolated from human
      faeces. These strains were characterized by phylogenetic analyses based on 16S
      rRNA gene sequence and phenotypic tests. 16S rRNA gene sequence analyses revealed
      that strains YIT 12056T, YIT 12057T and YIT 12058T were most closely related to
      the type strains of Bacteroides gallinarum, Bacteroides uniformis and Bacteroides
      intestinalis with approximate similarity values of 96.6, 95.0 and 96.7%,
      respectively. The DNA G+C contents of the novel strains were 45.3 (YIT 12056T),
      45.2 (YIT 12057T) and 43.6 mol% (YIT 12058T) and the major respiratory quinones
      of all three isolates were menaquinones MK-10 and MK-11. These properties were
      typical for members of the genus Bacteroides. The results of the other phenotypic
      analyses also supported the affiliation of these strains to the genus
      Bacteroides. The 16S rRNA gene sequence analysis, analysis of the major cellular
      fatty acids and other biochemical tests enabled the genotypic and phenotypic
      differentiation of the three new strains. Based on these data, three novel
      species, Bacteroides clarus sp. nov., Bacteroides fluxus sp. nov. and Bacteroides
      oleiciplenus sp. nov. are proposed. The type strains of B. clarus, B. fluxus and
      B. oleiciplenus are YIT 12056T (=JCM 16067T=DSM 22519T), YIT 12057T (=JCM
      16101T=DSM 22534T) and YIT 12058T (=JCM 16102T=DSM 22535T), respectively.

PMID- 19767356
TI  - Falsibacillus pallidus to replace the homonym Bacillus pallidus Zhou et al. 2008.
AB  - The prokaryotic species name Bacillus pallidus Zhou et al. 2008 is illegitimate
      because it is a later homonym of the name Bacillus pallidus Scholz et al. 1988
      (Bacteria, Firmicutes, Bacillales, Bacillaceae, Bacillus). Although Bacillus
      pallidus Scholz et al. 1988 was transferred to the genus Geobacillus as
      Geobacillus pallidus comb. nov. in 2004, the species name Bacillus pallidus
      Scholz et al. 1988 remains validly published and has priority at that position
      [Principle 8 of the Bacteriological Code (1990 Revision)]. In order to solve this
      problem, a new name was sought for this taxon, represented by the type strain CW
      7(T). In addition, the placement of this species in the genus Bacillus was
      reassessed. The data collected were re-examined as part of a taxonomic study
      using a polyphasic approach. It was concluded, primarily based on the
      chemotaxonomic data, that strain CW 7(T) did not belong to the genus Bacillus,
      but should be placed in a new genus, for which the name Falsibacillus gen. nov.
      is proposed. The genus currently comprises a single species, Falsibacillus
      pallidus comb. nov. represented by the type strain CW 7(T) (=KCTC 13200(T)=CCTCC
      AB 207188(T)=LMG 24451(T)).

PMID- 19767357
TI  - Reclassification of Flexibacter tractuosus (Lewin 1969) Leadbetter 1974 and
      'Microscilla sericea' Lewin 1969 in the genus Marivirga gen. nov. as Marivirga
      tractuosa comb. nov. and Marivirga sericea nom. rev., comb. nov.
AB  - The taxonomic position of the misclassified strains [Flexibacter] tractuosus KCTC
      2958T and '[Microscilla] sericea' LMG 13021 was studied using a polyphasic
      approach. The two strains shared 99.1% 16S rRNA gene sequence similarity and 28%
      DNA-DNA relatedness. On the basis of the phylogenetic evidence supported by
      genotypic and phenotypic data [Flexibacter] tractuosus KCTC 2958T and
      '[Microscilla] sericea' LMG 13021 are classified as two distinct species in a
      novel genus, Marivirga, in the family 'Flammeovirgaceae', as Marivirga tractuosa
      comb. nov. and Marivirga sericea nom. rev., comb. nov., with strains KCTC 2958T
      (=ATCC 23168T =CIP 106410T =DSM 4126T =NBRC 15989T =NCIMB 1408T =VKM B-1430T) and
      LMG 13021T (=ATCC 23182T =NBRC 15983T =NCIMB 1403T), respectively, as the type
      strains. The type species is Marivirga tractuosa.

PMID- 19767358
TI  - Saccharomonospora marina sp. nov., isolated from an ocean sediment of the East
      China Sea.
AB  - A novel, aerobic, Gram-positive actinomycete strain, designated XMU15T, was
      isolated from an ocean sediment collected from Zhaoan Bay in the East China Sea
      and was subjected to a polyphasic approach to determine its taxonomic position.
      The isolate grew optimally at 28 degrees C and at pH 7.0 in the presence of 3%
      (w/v) NaCl on ISP medium 2. Gelatin liquefaction, milk coagulation and nitrate
      reduction were positive. Cellulose and starch hydrolysis, hydrogen sulfide and
      melanin production, and catalase, urease and oxidase activities were negative.
      The predominant menaquinone of the isolate was MK-9 (H4), and meso-diaminopimelic
      acid was the diagnostic amino acid in the cell wall. The phospholipids of the
      isolate comprised diphosphatidylglycerol, phosphatidylglycerol,
      phosphatidylinositol, and a minor amount of phosphatidylethanolamine. The major
      fatty acids of the strain were iso-C16:0 (26.36%), C17:1omega6c (16.80%), C15:0
      (16.2%), C16:0 (8.90%), C17:1omega8c (7.69%) and iso-C16:1 H (5.95%). The DNA G+C
      content of the genomic DNA was 68.1 mol%. A phylogenetic tree based on 16S rRNA
      gene sequences showed that the isolate fell within the evolutionary radiation
      encompassed by the genus Saccharomonospora and showed the highest 16S rRNA gene
      sequence similarity (96.7%) to Saccharomonospora xinjiangensis DSM 44391T. Based
      on the results of 16S rRNA gene sequence analysis and phenotypic and genotypic
      characterization, strain XMU15T (=KCTC 19701T =CCTCC AA 209048T) represents a
      novel species of the genus Saccharomonospora, for which the name
      Saccharomonospora marina sp. nov. is proposed.

PMID- 19767359
TI  - Parapedobacter luteus sp. nov. and Parapedobacter composti sp. nov., isolated
      from cotton waste compost.
AB  - Two aerobic, Gram-reaction-negative, non-spore-forming bacterial strains, 4M29T
      and 4M40T, were isolated from cotton composts. The two strains grew in the
      presence of 0-5% (w/v) NaCl (optimum growth in the absence of NaCl), at pH 6.0
      8.0 (optimum, pH 7.0) and at 15-45 degrees C (optimum, 30 degrees C). The strains
      shared 97.1% 16S rRNA gene sequence similarity. Strains 4M29T and 4M40T showed
      the next highest levels of 16S rRNA gene sequence similarity to Parapedobacter
      koreensis Jip14T (95.6 and 94.4%, respectively) and Parapedobacter soli DCY14T
      (95.2 and 93.8%). The level of DNA-DNA relatedness between strains 4M29T and
      4M40T was 38%. The two strains contained iso-C15:0, summed feature 3 (comprising
      iso-C15:0 2-OH and/or C16:1omega7c) and iso-C17:0 3-OH as major fatty acids, MK-7
      as the major respiratory quinone, homospermidine as the only polyamine and
      phosphatidylethanolamine as the major polar lipid. The DNA G+C contents of
      strains 4M29T and 4M40T were 47.6 and 48.6 mol%, respectively. On the basis of
      phylogenetic and phenotypic data, strains 4M29T and 4M40T are considered to
      represent two novel species of the genus Parapedobacter, for which the names
      Parapedobacter luteus sp. nov. (type strain 4M29T =KACC 10955T =JCM 15977T) and
      Parapedobacter composti sp. nov. (type strain 4M40T =KACC 10972T =JCM 15978T) are
      proposed.

PMID- 19767360
TI  - Haliea mediterranea sp. nov., a marine gammaproteobacterium.
AB  - Strain 7SM29T, an aerobic marine gammaproteobacterium isolated from seawater from
      Castellon, Spain, was characterized by classical phenotyping, chemotaxonomy and
      16S rRNA gene sequence analysis. Strain 7SM29T was found to be closely related to
      strains in the genus Haliea and to Congregibacter litoralis KT71T, with which a
      genus-level cluster was formed within the NOR5/OM60 clade of the
      Gammaproteobacteria. Strain 7SM29T was a short, motile rod with a tuft of three
      polar flagella. The strain grew on marine agar and formed pale-yellow colonies.
      Strain 7SM29T required NaCl for growth, reduced nitrate to nitrite, degraded
      several polymers and showed a preference for organic acids and amino acids over
      carbohydrates as carbon and energy sources. Strain 7SM29T contained Q-8 as the
      sole respiratory quinone. The DNA G+C content was 62.1 mol%.
      Phosphatidylglycerol, diphosphatidylglycerol and phosphatidylethanolamine were
      the major polar lipids. The major cellular fatty acids were unsaturated C16-C18
      compounds. On the basis of extensive phenotypic and phylogenetic comparative
      analysis, it is concluded that the strain represents a novel species of the genus
      Haliea, for which the name Haliea mediterranea sp. nov. is proposed. The type
      strain is 7SM29T (=CECT 7447T =DSM 21924T).

PMID- 19767361
TI  - Arenicella xantha gen. nov., sp. nov., a gammaproteobacterium isolated from a
      marine sandy sediment.
AB  - A Gram-negative, aerobic, yellow-pigmented, rod-shaped, non-motile bacterium,
      strain KMM 3895T, was isolated from a marine sandy sample collected offshore from
      the Sea of Japan. Phylogenetic analysis based on the 16S rRNA gene sequence
      placed strain KMM 3895T in the class Gammaproteobacteria, forming a separate
      branch, sharing 89.5 % sequence similarity with Nitrincola lacisaponensis 4CAT
      and 88-87% similarity with the other members of the cluster, including members of
      Kangiella, Spongiibacter, Alcanivorax and Microbulbifer. The major isoprenoid
      quinone was Q-8. Polar lipids consisted of phosphatidylethanolamine,
      phosphatidylglycerol, diphosphatidylglycerol, aminophospholipid and an unknown
      phospholipid. Fatty acid analysis revealed C16:1omega7, iso-C16:0, iso-C18:0 and
      C18:1omega7 as dominant components. The DNA G+C content was determined to be 48.1
      mol%. Based on its unique phenotypic characteristics and phylogenetic distance,
      the marine coastal sediment isolate KMM 3895T should be classified as a
      representative of a novel genus and species, for which the name Arenicella xantha
      gen. nov., sp. nov. is proposed. The type strain of Arenicella xantha is KMM
      3895T (=NRIC 0759T =JCM 16153T).

PMID- 19767362
TI  - Brevundimonas halotolerans sp. nov., Brevundimonas poindexterae sp. nov. and
      Brevundimonas staleyi sp. nov., prosthecate bacteria from aquatic habitats.
AB  - Eight strains of Gram-negative, bacteroid-shaped, prosthecate bacteria, isolated
      from brackish water (MCS24T, MCS17 and MCS35), the marine environment (CM260,
      CM272 and CM282) and activated sludge (FWC40T and FWC43T), were characterized
      using a polyphasic approach. Analysis of 16S rRNA gene sequences determined that
      all strains were affiliated to the alphaproteobacterial genus Brevundimonas,
      forming three distinct phyletic lineages within the genus. The strains grew best
      with 5-30 g NaCl l(-1) at 20-30 degrees C. DNA G+C contents for strains MCS24T,
      FWC40T and FWC43T were between 65 and 67 mol%, in accordance with values reported
      previously for other species of the genus. Moreover, chemotaxonomic data and
      physiological and biochemical tests allowed the phenotypic differentiation of
      three novel species within the genus Brevundimonas, for which the names
      Brevundimonas halotolerans sp. nov. (type strain MCS24T =LMG 25346T =CCUG
      58273T), Brevundimonas poindexterae sp. nov. (type strain FWC40T =LMG 25261T
      =CCUG 57883T) and Brevundimonas staleyi sp. nov. (type strain FWC43T =LMG 25262T
      =CCUG 57884T) are proposed.

PMID- 19767363
TI  - Marinobacterium lutimaris sp. nov., isolated from a tidal flat.
AB  - A Gram-staining-negative, moderately halophilic bacterium, designated strain
      AN9T, was isolated from a tidal flat of the Taean coast in South Korea. Cells
      were catalase- and oxidase-positive short rods that were motile by means of a
      single polar flagellum. Growth of strain AN9T was observed at 15-40 degrees C
      (optimum, 25-30 degrees C) and at pH 6.0-8.0 (optimum, pH 6.5-7.5). Strain AN9T
      contained ubiquinone Q-8 as the predominant isoprenoid quinone and C10:0 3-OH
      (31.7%), C18:1omega7c (24.8%), C16:0 (14.7%) and summed feature 3 (comprising
      C16:1omega7c and/or iso-C15:0 2-OH, 10.72%) as the major fatty acids. The G+C
      content of the genomic DNA of strain AN9T was 58 mol%. Phylogenetic analysis
      based on 16S rRNA gene sequences showed that strain AN9T was related to members
      of the genus Marinobacterium and was related most closely to Marinobacterium
      litorale IMCC1877T (96.8% similarity). On the basis of chemotaxonomic and
      molecular data, strain AN9T is considered to represent a novel species of the
      genus Marinobacterium, for which the name Marinobacterium lutimaris sp. nov. is
      proposed. The type strain is AN9T (=KACC 13703T =DSM 22012T).

PMID- 19767365
TI  - Thermosporothrix hazakensis gen. nov., sp. nov., isolated from compost,
      description of Thermosporotrichaceae fam. nov. within the class Ktedonobacteria
      Cavaletti et al. 2007 and emended description of the class Ktedonobacteria.
AB  - We isolated from compost an aerobic, thermophilic, Gram-stain-positive, spore
      forming bacterium that formed branched vegetative and aerial mycelia. This
      strain, designated SK20-1T, grew at 31-58 degrees C, with optimum growth at 50
      degrees C, while no growth was observed below 28 or above 60 degrees C. The pH
      range for growth was 5.4-8.7, with optimum growth at pH 7.0, while no growth was
      observed below pH 5.0 or above pH 9.1. Strain SK20-1T was able to hydrolyse
      polysaccharides such as cellulose, xylan and chitin. The DNA G+C content was 54.0
      mol%. The major fatty acid was iso-C17:0 and the major menaquinone was MK-9(H2).
      The cell wall contained glutamic acid, serine, alanine and ornithine in a molar
      ratio of 1.00:1.07:2.64:0.83. The polar lipids consisted of phosphatidylinositol,
      phosphatidylinositol mannosides, phosphatidylglycerol, diphosphatidylglycerol and
      an unknown glycolipid. Cell-wall sugars were rhamnose and mannose. Detailed
      phylogenetic analysis based on 16S rRNA gene sequences indicated that strain SK20
      1T belongs to the class Ktedonobacteria, and that the strain is most closely
      related to Ktedonobacter racemifer SOSP1-21(T) (88.5 %). On the basis of its
      phenotypic features and phylogenetic position, we propose that SK20-1T represents
      a novel genus and species, Thermosporothrix hazakensis gen. nov., sp. nov.,
      within the new family Thermosporotrichaceae fam. nov. The type strain of
      Thermosporothrix hazakensis is strain SK20-1(T) (=JCM 16142T =ATCC BAA-1881T). In
      addition, we propose an emended description of the class Ktedonobacteria to
      classify the class in the phylum Chloroflexi.

PMID- 19767366
TI  - Natronorubrum sediminis sp. nov., an archaeon isolated from a saline lake.
AB  - Two novel haloalkaliphilic archaea, strains CG-6T and CG-4, were isolated from
      sediment of the hypersaline Lake Chagannor in Inner Mongolia, China. Cells of the
      two strains were pleomorphic, non-motile and strictly aerobic. They required at
      least 2.5 M NaCl for growth, with optimum growth at 3.4 M NaCl. They grew at pH
      8.0-11.0, with optimum growth at pH 9.0. Hypotonic treatment with less than 1.5 M
      NaCl caused cell lysis. The two strains had similar polar lipid compositions,
      possessing C20C20 and C20C25 derivatives of phosphatidylglycerol and
      phosphatidylglycerol phosphate methyl ester. No glycolipids were detected.
      Comparison of 16S rRNA gene sequences and morphological features placed them in
      the genus Natronorubrum. 16S rRNA gene sequence similarities to strains of
      recognized species of the genus Natronorubrum were 96.2-93.8%. Detailed
      phenotypic characterization and DNA-DNA hybridization studies revealed that the
      two strains belong to a novel species in the genus Natronorubrum, for which the
      name Natronorubrum sediminis sp. nov. is proposed; the type strain is CG-6T
      (=CECT 7487T =CGMCC 1.8981T =JCM 15982T).

PMID- 19767367
TI  - Verrucosispora sediminis sp. nov., a cyclodipeptide-producing actinomycete from
      deep-sea sediment.
AB  - An actinomycete, designated MS426T, the culture broth of which showed potent
      antimicrobial activity, was isolated from a deep-sea sediment sample of the South
      China Sea. An almost-complete sequence of the 16S rRNA gene of strain MS426T was
      determined and aligned with those of representatives of the family
      Micromonosporaceae available in public databases. Phylogenetic trees were
      inferred by using three algorithms. Strain MS426T formed a branch adjacent to
      Verrucosispora lutea YIM 013T in a distinct cluster occupied only by strains of
      the genus Verrucosispora. Strain MS426T was distinguishable from the type strains
      of the two described Verrucosispora species by using a combination of chemical
      and morphological markers and by DNA-DNA relatedness. On the basis of these
      genotypic and phenotypic differences, the novel antimicrobial strain with
      pharmaceutical potential represents a novel species, for which the name
      Verrucosispora sediminis sp. nov. is proposed. The type strain is MS426T (=CGMCC
      4.3550T =JCM 15670T).

PMID- 19767368
TI  - Haloplanus vescus sp. nov., an extremely halophilic archaeon from a marine solar
      saltern, and emended description of the genus Haloplanus.
AB  - An extremely halophilic archaeon, strain RO5-8T, was isolated from a disused
      marine solar saltern in China. The cells were pleomorphic and flat. In static
      liquid medium, cells floated to the surface. Strain RO5-8T stained Gram-negative
      and colonies were pink-pigmented. It was able to grow at 30-50 degrees C (optimum
      40 degrees C), at 2.6-4.3 M NaCl (optimum 3.1 M NaCl), at 0.03-0.5 M MgCl2
      (optimum 0.03 M MgCl2) and at pH 5.5-7.5 (optimum pH 6.0-6.5). Cells lysed in
      distilled water and the minimal NaCl concentration to prevent cell lysis was 12%
      (w/v). The major polar lipids of strain RO5-8T were phosphatidylglycerol,
      phosphatidylglycerol phosphate methyl ester, phosphatidylglycerol sulfate and one
      major glycolipid chromatographically identical to the sulfated mannosyl glucosyl
      diether S-DGD-1. On the basis of 16S rRNA gene sequence analysis, strain RO5-8T
      was closely related to three strains of Haloplanus natans with similarities of
      97.3-97.6%. The DNA G+C content of strain RO5-8T was 62.1 mol%. The DNA-DNA
      hybridization value between strain RO5-8T and Haloplanus natans JCM 14081T was
      51.6%. It was concluded that strain RO5-8T represents a novel species of the
      genus Haloplanus, for which the name Haloplanus vescus sp. nov. is proposed. The
      type strain is RO5-8T (=CGMCC 1.8712T =JCM 16055T).

PMID- 19767369
TI  - Poison control centers suffer state budget cuts.

PMID- 19767370
TI  - Drug approved to treat infantile spasms.

PMID- 19767372
TI  - Fiscally challenged drug-donation program helps needy Wyoming residents.

PMID- 19767373
TI  - Informatics in clinical instruction.

PMID- 19767374
TI  - Autoimmune hemolytic anemia associated with a formulation of traditional Chinese
      medicines.
AB  - PURPOSE: A case of autoimmune hemolytic anemia (AIHA) after treatment with a
      Chinese herbal preparation is reported. SUMMARY: A 29-year-old woman was admitted
      to the hospital with the primary complaints of jaundice, tea-colored urine, and
      fatigue lasting 10 days. Thirteen days prior, she went to a local private clinic
      seeking treatment for mild stomach pain and general malaise and was given weidean
      tablets. She took four tablets of weidean, a Chinese herbal preparation, orally
      three times daily for 2 days. After 2 days, she experienced fatigue, dizziness,
      and chest distress and subsequently discontinued treatment. Upon examination, she
      exhibited mild scleral and mucosal icterus. Her conjunctivas were pale, and her
      skin was slightly jaundiced. Preliminary laboratory tests found a low hemoglobin
      level and an elevated reticulocyte count. Biochemical tests showed an elevated
      total serum bilirubin concentration with indirect hyperbilirubinemia. Coombs'
      test results were positive for immunoglobulin G but negative for C3. All other
      test results were normal. The patient was diagnosed with AIHA secondary to
      weidean use, and she was treated promptly with oral prednisone, i.v. cimetidine,
      and oral sodium bicarbonate tablets. Seven days later, she showed clinical
      improvement. Her hemoglobin level rapidly increased to above 100 g/L, with a
      corresponding decrease in her reticulocyte count and serum bilirubin value over
      the next 8 days. She was discharged 15 days after admission and was asymptomatic
      at a three-week follow-up visit. CONCLUSION: Weidean, a formulation of Chinese
      medicinal herbs and other constituents, was associated with AIHA in a woman
      taking the remedy for gastritis.

PMID- 19767375
TI  - Possible montelukast-induced angioedema.
AB  - PURPOSE: A possible case of montelukast-induced angioedema is reported. SUMMARY:
      A 46-year-old woman with a history of severe allergies, including food allergies,
      and angioedema was evaluated at the emergency department (ED) for an acute
      episode of angioedema. Upon arrival at the ED, the patient had severe jaw
      tightness, facial numbness, uncontrollable cheek lifting, swollen eyes, and a
      swollen protruding tongue and was unable to catch her breath. Her dyspnea was
      apparent, and she was unable to talk and instead used hand and face gestures for
      affirmative and negative responses. The patient was treated with 0.3 mg
      epinephrine intramuscularly into the right thigh. After treatment, she had a
      temperature of 37 degrees C, a pulse of 90 beats/ min, a blood pressure value of
      100/59 mm Hg, a respiratory rate of 16 breaths/min, and 100% oxygen saturation on
      room air. After stabilization, she reported that her allergies had been
      adequately controlled with ebastine 10 mg daily, montelukast 10 mg daily, and
      vitamins (unspecified). The patient reported that since she started montelukast
      one month prior, she experienced three similar episodes, the first occurring five
      days after starting the drug. She mentioned being diagnosed and adequately
      treated these three times in the ED for angioedema. The patient denied any
      changes in eating habits or in her medications except for starting montelukast.
      She was observed at the ED for an hour and then discharged after stabilization on
      hydroxyzine hydrochloride 25 mg orally daily and fexofenadine hydrochloride 180
      mg orally daily. Montelukast was discontinued. CONCLUSION: A patient developed
      angioedema four times during one month of treatment with montelukast.

PMID- 19767376
TI  - Mortality, length of hospitalization, and costs associated with invasive fungal
      infections in high-risk patients.
AB  - PURPOSE: The mortality, length of hospitalization, and costs associated with
      invasive fungal infections (IFIs) in hospitalized patients were studied. METHODS:
      This retrospective database study used data from the 2004 Healthcare Cost and
      Utilization Project Nationwide In-patient Sample. Patients were selected for
      inclusion based on diagnostic codes corresponding to an IFI. A control group was
      matched to the IFI group based on high-risk conditions (i.e., cancer, infection
      with human immunodeficiency virus, chronic obstructive pulmonary disease,
      diabetes mellitus, and solid-organ, hematopoietic stem cell, or bone marrow
      transplant), age, sex, and hospital region and teaching status. Excess mortality,
      length of hospital stay, and costs were estimated as the differences between the
      IFI and control groups. RESULTS: A total of 11,881 patients were identified with
      a discharge diagnosis of an IFI who could be matched to a control. Frequent
      infections included candidiasis (40.2%), other mycoses (36.3%), and aspergillosis
      (16.4%). Patients with IFIs had a significantly higher mortality rate (15% versus
      5%), mean +/- S.E. length of stay (18.7 +/- 0.4 days versus 7.3 +/- 0.1 days),
      and mean +/- S.E. costs ($44,726 +/- $1,255 versus $15,445 +/- $404) (p < 0.001
      for all comparisons) than did patients without IFIs. The burden of IFIs varied by
      high-risk condition (highest for transplant recipients and patients with cancer)
      and type of infection (highest for candidiasis, zygomycosis, and aspergillosis).
      CONCLUSION: Examination of a large database showed that, compared with high-risk
      patients without IFIs, those with IFIs had higher mortality, a longer hospital
      stay, and higher costs associated with their hospitalization.

PMID- 19767377
TI  - Update on the status of 89 drug information centers in the United States.
AB  - PURPOSE: Previously identified U.S. drug information centers (DICs) were surveyed
      to determine whether they were still in existence and whether changes had
      occurred in the DICs since 2003. METHODS: Eighty-nine DICs identified in a 2003
      survey were surveyed in April 2008. For DICs still in existence, questions were
      designed to determine whether there were changes in the mission, time spent on
      activities, staffing, and drug information questions (number, complexity, and
      time required to answer) compared with five years earlier. Respondents' projected
      need for their DIC over the next five years was also surveyed. RESULTS: Seventy
      five (84%) of the 89 DICs were still active. The most notable changes in
      activities were increases in time spent on educating health-professions students
      (53%), supporting the institution's medication safety program (44%), and
      providing information-systems support (36%). The majority of respondents (73%)
      reported no change in the number of employed drug information personnel. The
      percentages of DICs reporting an increase, decrease, and no change in the number
      of drug information requests received were 29%, 42%, and 29%, respectively.
      Seventy percent reported an increase in the number of complex questions, while
      53% reported an increase in the time required to answer each question. Ninety
      seven percent of respondents projected no change or an increase in the need for
      their DIC over the next five years. CONCLUSION: Eighty-four percent of the
      previously identified DICs were still in existence. The most notable changes in
      these DICs were increases in the number of DICs focusing on educating health
      professions students, the complexity of drug information questions, and the
      amount of time required to answer each request.

PMID- 19767378
TI  - Long-term stability of extemporaneously prepared captopril oral liquids in glass
      bottles.
AB  - PURPOSE: The long-term stability of captopril in extemporaneously prepared oral
      liquids was studied. METHODS: Captopril solutions of 1 and 5 mg/mL were prepared
      in sterile water for irrigation with sorbitol, disodium edetate, and sodium
      benzoate. The samples were stored in 100-mL amber glass bottles with a headspace
      of air at 22 degrees C for 12 months. The captopril concentration was determined
      by high-performance liquid chromatography at 0, 3, 6, 9, and 12 months. The pH of
      the solutions was also measured, and the physical appearance was recorded. The
      stability of the 1-mg/mL captopril preparation during 1 month of simulated use
      when stored at 2-8 degrees C was tested at the start and the end of the 12-month
      study period. Chemical stability was defined as retention of at least 90% of the
      initial captopril concentration. The microbiological quality of the preparations
      was tested at 0, 6, and 12 months (1 mg/mL) and 0 and 12 months (5 mg/mL).
      RESULTS: Throughout the 12-month study period, the captopril concentration in the
      oral liquids exceeded 90% of the initial concentration. The lowest concentration
      (98.5%) was detected in the 5-mg/mL preparation after 3 months of storage. The 1
      mg/mL preparation was stable during 1 month of simulated use, both at the start
      and the end of the 12-month study period. No microbiological growth was observed
      in any of the samples tested. CONCLUSION: Extemporaneously prepared oral liquid
      formulations of captopril 1 and 5 mg/mL were chemically stable when stored in
      glass bottles at room temperature for 12 months when stabilized with 0.1 mg/ mL
      disodium edetate at a low pH.

PMID- 19767379
TI  - Significant publications on infectious diseases pharmacotherapy in 2008.
AB  - PURPOSE: Significant publications on infectious diseases (ID) pharmacotherapy in
      2008 were compiled and summarized. SUMMARY: On December 31, 2008, the Houston
      Infectious Diseases Network compiled a listing of published articles identified
      as having a significant impact on ID pharmacotherapy. The publication period was
      limited to January 1 through December 31, 2008. Articles were selected based on
      prior presentations at ID and pharmacy meetings or were listed as major articles
      in prominent ID journals. Priority was given to articles that were published in
      peer-reviewed journals and to treatment guidelines endorsed by major medical and
      pharmacy organizations. A bibliography of 56 articles (40 not related to human
      immunodeficiency virus [HIV] infection and 16 related to HIV infection) was
      distributed to members of the Society of Infectious Diseases Pharmacists (SIDP)
      via an Internet survey in early January 2009. Members were asked to select 10
      publications not related to HIV infection and 1 HIV-related publication that they
      believed made the greatest contribution to the antimicrobial-related medical
      literature in 2008. A total of 115 SIDP members participated in the survey.
      Summaries of the top articles selected, along with an interpretation of their
      effect on clinical practice, are included. CONCLUSION: The increasing number of
      articles in the peer-reviewed medical literature related to the diagnosis and
      treatment of ID has made it challenging to maintain a contemporary knowledge base
      of key publications. This summary of significant ID articles published in 2008
      can help to alleviate this burden.

PMID- 19767380
TI  - Pharmacists' role in facilitating evidence-based prescribing for unlabeled use of
      medications.

PMID- 19767381
TI  - Electronic cigarettes: safety concerns and regulatory issues.

PMID- 19767382
TI  - Using National Drug Codes and drug knowledge bases to organize prescription
      records from multiple sources.
AB  - PURPOSE: The utility of National Drug Codes (NDCs) and drug knowledge bases
      (DKBs) in the organization of prescription records from multiple sources was
      studied. METHODS: The master files of most pharmacy systems include NDCs and
      local codes to identify the products they dispense. We obtained a large sample of
      prescription records from seven different sources. These records carried a
      national product code or a local code that could be translated into a national
      product code via their formulary master. We obtained mapping tables from five
      DKBs. We measured the degree to which the DKB mapping tables covered the national
      product codes carried in or associated with the sample of prescription records.
      RESULTS: Considering the total prescription volume, DKBs covered 93.0-99.8% of
      the product codes from three outpatient sources and 77.4-97.0% of the product
      codes from four inpatient sources. Among the in-patient sources, invented codes
      explained 36-94% of the noncoverage. Outpatient pharmacy sources rarely invented
      codes, which comprised only 0.11-0.21% of their total prescription volume,
      compared with inpatient pharmacy sources for which invented codes comprised 1.7
      7.4% of their prescription volume. The distribution of prescribed products was
      highly skewed, with 1.4-4.4% of codes accounting for 50% of the message volume
      and 10.7-34.5% accounting for 90% of the message volume. CONCLUSION: DKBs cover
      the product codes used by outpatient sources sufficiently well to permit
      automatic mapping. Changes in policies and standards could increase coverage of
      product codes used by inpatient sources.

PMID- 19767383
TI  - Determining the feasibility of robotic courier medication delivery in a hospital
      setting.
AB  - PURPOSE: The feasibility of a robotic courier medication delivery system in a
      hospital setting was evaluated. SUMMARY: Robotic couriers are self-guiding, self
      propelling robots that navigate hallways and elevators to pull an attached or
      integrated cart to a desired destination. A robotic courier medication delivery
      system was pilot tested in two patient care units at a 471-bed tertiary care
      academic medical center. Average transit for the existing manual medication
      delivery system hourly hospitalwide deliveries was 32.6 minutes. Of this, 32.3%
      was spent at the patient care unit and 67.7% was spent pushing the cart or
      waiting at an elevator. The robotic courier medication delivery system traveled
      as fast as 1.65 ft/sec (52% speed of the manual system) in the absence of
      barriers but moved at an average rate of 0.84 ft/sec (26% speed of the manual
      system) during the study, primarily due to hallway obstacles. The robotic courier
      was utilized for 50% of the possible 1750 runs during the 125-day pilot due to
      technical or situational difficulties. Of the runs that were sent, a total of 79
      runs failed, yielding an overall 91% success rate. During the final month of the
      pilot, the success rate reached 95.6%. Customer satisfaction with the traditional
      manual delivery system was high. Customer satisfaction with deliveries declined
      after implementation of the robotic courier medication distribution system.
      CONCLUSION: A robotic courier medication delivery system was implemented but was
      not expanded beyond the two pilot units. Challenges of implementation included
      ongoing education on how to properly move the robotic courier and keeping the
      hallway clear of obstacles.

PMID- 19767384
TI  - Incremental value of continuous glucose monitoring when starting pump therapy in
      patients with poorly controlled type 1 diabetes: the RealTrend study.
AB  - OBJECTIVE: To compare the improvements in glycemic control associated with
      transitioning to insulin pump therapy in patients using continuous glucose
      monitoring versus standard blood glucose self-monitoring. RESEARCH DESIGN AND
      METHODS: The RealTrend study was a 6-month, randomized, parallel-group, two-arm,
      open-label study of 132 adults and children with uncontrolled type 1 diabetes
      (A1C >or=8%) being treated with multiple daily injections. One group was fitted
      with the Medtronic MiniMed Paradigm REAL-Time system (PRT group), an insulin pump
      with integrated continuous subcutaneous glucose monitoring (CGM) capability, with
      instructions to wear CGM sensors at least 70% of the time. Conventional insulin
      pump therapy was initiated in the other group (continuous subcutaneous insulin
      infusion [CSII] group). Outcome measures included A1C and glycemic variability.
      RESULTS: A total of 115 patients completed the study. Between baseline and trial
      end, A1C improved significantly in both groups (PRT group -0.81 +/- 1.09%, P <
      0.001; CSII group -0.57 +/- 0.94%, P < 0.001), with no significant difference
      between groups. When the 91 patients who were fully protocol-compliant (including
      CGM sensor wear >or=70% of the time) were considered, A1C improvement was
      significantly greater in the PRT group (P = 0.004) (PRT group -0.96 +/- 0.93%, P
      < 0.001; CSII group -0.55 +/- 0.93%, P < 0.001). Hyperglycemia parameters
      decreased in line with improvements in A1C with no impact on hypoglycemia.
      CONCLUSIONS: CGM-enabled insulin pump therapy improves glycemia more than
      conventional pump therapy during the first 6 months of pump use in patients who
      wear CGM sensors at least 70% of the time.

PMID- 19767385
TI  - The variegated mutants lacking chloroplastic FtsHs are defective in D1
      degradation and accumulate reactive oxygen species.
AB  - In the photosynthetic apparatus, a major target of photodamage is the D1 reaction
      center protein of photosystem II (PSII). Photosynthetic organisms have developed
      a PSII repair cycle in which photodamaged D1 is selectively degraded. A thylakoid
      membrane-bound metalloprotease, FtsH, was shown to play a critical role in this
      process. Here, the effect of FtsHs in D1 degradation was investigated in
      Arabidopsis (Arabidopsis thaliana) mutants lacking FtsH2 (yellow variegated2
      [var2]) or FtsH5 (var1). Because these mutants are characterized by variegated
      leaves that sometimes complicate biochemical studies, we employed another
      mutation, fu-gaeri1 (fug1), that suppresses leaf variegation in var1 and var2 to
      examine D1 degradation. Two-dimensional blue native PAGE showed that var2 has
      less PSII supercomplex and more PSII intermediate lacking CP43, termed RC47, than
      the wild type under normal growth light. Moreover, our histochemical and
      quantitative analyses revealed that chloroplasts in var2 accumulate significant
      levels of reactive oxygen species, such as superoxide radical and hydrogen
      peroxide. These results indicate that the lack of FtsH2 leads to impaired D1
      degradation at the step of RC47 formation in PSII repair and to photooxidative
      stress even under nonphotoinhibitory conditions. Our in vivo D1 degradation
      assays, carried out by nonvariegated var2 fug1 and var1 fug1 leaves, demonstrated
      that D1 degradation was impaired in different light conditions. Taken together,
      our results suggest the important role of chloroplastic FtsHs, which was not
      precisely examined in vivo. Attenuated D1 degradation in the nonvariegated
      mutants also suggests that leaf variegation seems to be independent of the PSII
      repair.

PMID- 19767386
TI  - Metabolite sorting of a germplasm collection reveals the hydroxylase3 locus as a
      new target for maize provitamin A biofortification.
AB  - Vitamin A deficiency, a global health burden, can be alleviated through
      provitamin A carotenoid biofortification of major crop staples such as maize (Zea
      mays) and other grasses in the Poaceae. If regulation of carotenoid biosynthesis
      was better understood, enhancement could be controlled by limiting beta-carotene
      hydroxylation to compounds with lower or no nonprovitamin A activity. Natural
      maize genetic diversity enabled identification of hydroxylation genes associated
      with reduced endosperm provitamin A content. A novel approach was used to capture
      the genetic and biochemical diversity of a large germplasm collection,
      representing 80% of maize genetic diversity, without having to sample the entire
      collection. Metabolite data sorting was applied to select a 10-line genetically
      diverse subset representing biochemical extremes for maize kernel carotenoids.
      Transcript profiling led to discovery of the Hydroxylase3 locus that coincidently
      mapped to a carotene quantitative trait locus, thereby prompting investigation of
      allelic variation in a broader collection. Three natural alleles in 51 maize
      lines explained 78% of variation and approximately 11-fold difference in beta
      carotene relative to beta-cryptoxanthin and 36% of the variation and 4-fold
      difference in absolute levels of beta-carotene. A simple PCR assay to track and
      identify Hydroxylase3 alleles will be valuable for predicting nutritional content
      in genetically diverse cultivars found worldwide.

PMID- 19767387
TI  - Pea has its tendrils in branching discoveries spanning a century from auxin to
      strigolactones.

PMID- 19767388
TI  - Influence of recent exercise and skin temperature on ultrasound Doppler
      measurements in patients with rheumatoid arthritis--an intervention study.
AB  - OBJECTIVE: Use of ultrasound Doppler (USD) in diagnosing and treatment monitoring
      of patients with RA has increased considerably. Hyperaemia is an integral part of
      the inflammatory response, and the amount of USD activity in an inflamed synovium
      may therefore be used to quantify the inflammatory activity. It is unclear,
      however, whether the hyperaemia alone reflects the disease activity or may be
      influenced by other factors. METHODS: Twenty-nine patients with RA underwent USD
      examination of the wrist before and immediately after three interventions. The
      interventions were carried out on three separate days. The interventions were (i)
      isometric exercise of the muscles of the hand and forearm, (ii) heating and (iii)
      cooling of the hand. The amount of Doppler in the wrist joint was quantified by
      measuring the percentage of colour in the synovium-the colour fraction (CF). The
      CF values estimated before and after each intervention were compared to see if
      any intervention affected the amount of Doppler in the synovium. RESULTS: The CF
      decreased significantly after cooling of the hand (P = 0.018 and <0.0001).
      Despite being highly significant, the numerical decrease in CF was only modest,
      0.78-1.33 percentage points. The other interventions did not affect the CF
      significantly, with P-values of 0.65 and 0.59 in the heating intervention and
      0.49 in the exercise intervention. CONCLUSIONS: Cooling of the hand should, if
      possible, be avoided before a USD examination of the wrist in patients with RA,
      because the amount of Doppler activity might be affected by low skin
      temperatures.

PMID- 19767389
TI  - Asparagine-linked oligosaccharides present on a non-consensus amino acid sequence
      in the CH1 domain of human antibodies.
AB  - We report that N-linked oligosaccharide structures can be present on an
      asparagine residue not adhering to the consensus site motif NX(S/T), where X is
      not proline, described in the literature. We have observed oligosaccharides on a
      non-consensus asparaginyl residue in the C(H)1 constant domain of IgG1 and IgG2
      antibodies. The initial findings were obtained from characterization of charge
      variant populations evident in a recombinant human antibody of the IgG2 subclass.
      HPLC-MS results indicated that cation-exchange chromatography acidic variant
      populations were enriched in antibody with a second glycosylation site, in
      addition to the well documented canonical glycosylation site located in the C(H)2
      domain. Subsequent tryptic and chymotryptic peptide map data indicated that the
      second glycosylation site was associated with the amino acid sequence
      TVSWN(162)SGAL in the C(H)1 domain of the antibody. This highly atypical
      modification is present at levels of 0.5-2.0% on most of the recombinant
      antibodies that have been tested and has also been observed in IgG1 antibodies
      derived from human donors. Site-directed mutagenesis of the C(H)1 domain sequence
      in a recombinant-human IgG1 antibody resulted in an increase in non-consensus
      glycosylation to 3.15%, a greater than 4-fold increase over the level observed in
      the wild type, by changing the -1 and +1 amino acids relative to the asparagine
      residue at position 162. We believe that further understanding of the phenomenon
      of non-consensus glycosylation can be used to gain fundamental insights into the
      fidelity of the cellular glycosylation machinery.

PMID- 19767390
TI  - Massive formation of intracellular membrane vesicles in Escherichia coli by a
      monotopic membrane-bound lipid glycosyltransferase.
AB  - The morphology and curvature of biological bilayers are determined by the packing
      shapes and interactions of their participant molecules. Bacteria, except
      photosynthetic groups, usually lack intracellular membrane organelles. Strong
      overexpression in Escherichia coli of a foreign monotopic glycosyltransferase
      (named monoglycosyldiacylglycerol synthase), synthesizing a nonbilayer-prone
      glucolipid, induced massive formation of membrane vesicles in the cytoplasm.
      Vesicle assemblies were visualized in cytoplasmic zones by fluorescence
      microscopy. These have a very low buoyant density, substantially different from
      inner membranes, with a lipid content of > or = 60% (w/w). Cryo-transmission
      electron microscopy revealed cells to be filled with membrane vesicles of various
      sizes and shapes, which when released were mostly spherical (diameter
      approximately 100 nm). The protein repertoire was similar in vesicle and inner
      membranes and dominated by the glycosyltransferase. Membrane polar lipid
      composition was similar too, including the foreign glucolipid. A related
      glycosyltransferase and an inactive monoglycosyldiacylglycerol synthase mutant
      also yielded membrane vesicles, but without glucolipid synthesis, strongly
      indicating that vesiculation is induced by the protein itself. The high capacity
      for membrane vesicle formation seems inherent in the glycosyltransferase
      structure, and it depends on the following: (i) lateral expansion of the inner
      monolayer by interface binding of many molecules; (ii) membrane expansion through
      stimulation of phospholipid synthesis, by electrostatic binding and sequestration
      of anionic lipids; (iii) bilayer bending by the packing shape of excess
      nonbilayer-prone phospholipid or glucolipid; and (iv) potentially also the shape
      or penetration profile of the glycosyltransferase binding surface. These features
      seem to apply to several other proteins able to achieve an analogous membrane
      expansion.

PMID- 19767391
TI  - Roles of Tom70 in import of presequence-containing mitochondrial proteins.
AB  - Mitochondrial protein traffic requires precise recognition of the mitochondrial
      targeting signals by the import receptors on the mitochondrial surface including
      a general import receptor Tom20 and a receptor for presequence-less proteins,
      Tom70. Here we took a proteome-wide approach of mitochondrial protein import in
      vitro to find a set of presequence-containing precursor proteins for recognition
      by Tom70. The presequences of the Tom70-dependent precursor proteins were
      recognized by Tom20, whereas their mature parts exhibited Tom70-dependent import
      when attached to the presequence of Tom70-independent precursor proteins. The
      mature parts of the Tom70-dependent precursor proteins have the propensity to
      aggregate, and the presence of the receptor domain of Tom70 prevents their
      aggregate formation. Therefore Tom70 plays the role of a docking site for not
      only cytosolic chaperones but also aggregate-prone substrates to maintain their
      solubility for efficient transfer to downstream components of the mitochondrial
      import machineries.

PMID- 19767392
TI  - Complex phosphatase regulation of Ca2+-activated Cl- currents in pulmonary
      arterial smooth muscle cells.
AB  - The present study was undertaken to determine whether the two ubiquitously
      expressed Ca(2+)-independent phosphatases PP1 and PP2A regulate Ca(2+)-activated
      Cl(-) currents (I(Cl(Ca))) elicited by 500 nM [Ca(2+)](i) in rabbit pulmonary
      artery (PA) myocytes dialyzed with or without 3 mM ATP. Reverse transcription-PCR
      experiments revealed the expression of PP1alpha, PP1beta/delta, PP1gamma,
      PP2Aalpha, PP2Abeta, PP2Balpha (calcineurin (CaN) Aalpha), and PP2Bbeta (CaN
      Abeta) but not PP2Bgamma (CaN Agamma) in rabbit PA. Western blot and
      immunofluorescence experiments confirmed the presence of all three PP1 isoforms
      and PP2A. Intracellular dialysis with a peptide inhibitor of calcineurin (CaN
      AIP); the non-selective PP1/PP2A inhibitors okadaic acid (0.5, 10, or 30 nM),
      calyculin A (10 nM), or cantharidin (100 nM); and the selective PP1 inhibitor
      NIPP-1 (100 pM) potently antagonized the recovery of I(Cl(Ca)) in cells dialyzed
      with no ATP, whereas the PP2A-selective antagonist fostriecin (30 or 150 nM) was
      ineffective. The combined application of okadaic acid (10 nM) and CaN
      autoinhibitory peptide (50 microM) did not potentiate the response of I(Cl(Ca))
      in 0 ATP produced by maximally inhibiting CaN or PP1/PP2A alone. Consistent with
      the non-additive effects of either classes of phosphatases, the PP1 inhibitor
      NIPP-1 (100 pM) antagonized the recovery of I(Cl(Ca)) induced by exogenous CaN
      Aalpha (0.5 microM). These results demonstrate that I(Cl(Ca)) in PA myocytes is
      regulated by CaN and PP1 and/or PP2A. Our data also suggest the existence of a
      functional link between these two classes of phosphatases.

PMID- 19767393
TI  - Molecular basis for zinc transporter 1 action as an endogenous inhibitor of L
      type calcium channels.
AB  - The L-type calcium channel (LTCC) has a variety of physiological roles that are
      critical for the proper function of many cell types and organs. Recently, a
      member of the zinc-regulating family of proteins, ZnT-1, was recognized as an
      endogenous inhibitor of the LTCC, but its mechanism of action has not been
      elucidated. In the present study, using two-electrode voltage clamp recordings in
      Xenopus oocytes, we demonstrate that ZnT-1-mediated inhibition of the LTCC
      critically depends on the presence of the LTCC regulatory beta-subunit. Moreover,
      the ZnT-1-induced inhibition of the LTCC current is also abolished by excess
      levels of the beta-subunit. An interaction between ZnT-1 and the beta-subunit, as
      demonstrated by co-immunoprecipitation and by fluorescence resonance energy
      transfer, is consistent with this result. Using surface biotinylation and total
      internal reflection fluorescence microscopy in HEK293 cells, we show a ZnT-1
      dependent decrease in the surface expression of the pore-forming alpha(1)-subunit
      of the LTCC. Similarly, a decrease in the surface expression of the alpha(1)
      subunit is observed following up-regulation of the expression of endogenous ZnT-1
      in rapidly paced cultured cardiomyocytes. We conclude that ZnT-1-mediated
      inhibition of the LTCC is mediated through a functional interaction of ZnT-1 with
      the LTCC beta-subunit and that it involves a decrease in the trafficking of the
      LTCC alpha(1)-subunit to the surface membrane.

PMID- 19767394
TI  - Mechanism for endogenously expressed ApoE modulation of adipocyte very low
      density lipoprotein metabolism: role in endocytic and lipase-mediated metabolic
      pathways.
AB  - Triglyceride-rich lipoproteins distribute energy in the form of fatty acids to
      peripheral tissues. We have previously shown that the absence of endogenous
      adipocyte apoE expression impairs adipocyte triglyceride acquisition from apoE
      containing triglyceride-rich lipoproteins in vitro and in vivo. Studies were
      performed to evaluate the mechanism(s) for this impairment. We excluded a role
      for secreted apoE in accounting for the difference in very low density
      lipoprotein (VLDL)-induced adipocyte triglyceride accumulation using cross
      incubation studies to show that secreted apoE did not enhance triglyceride
      synthesis in apoE knockout (EKO) adipocytes incubated with apoE-containing VLDL.
      Subsequent experiments established that both endocytic and lipase-mediated
      pathways for lipid acquisition from VLDL were impaired in EKO adipocytes. Binding
      and internalization of VLDL to EKO adipocytes were significantly lower due to
      decreased expression or redistribution of low density lipoprotein receptor family
      proteins. An important role for the VLDL receptor for contributing to differences
      in VLDL binding between wild-type and EKO adipocytes was identified. Lipoprotein
      lipase-dependent adipocyte lipogenesis was also significantly decreased in EKO
      adipocytes even though they secreted as much or more lipolytic activity. This
      decrease was related to impaired fatty acid internalization in EKO cells.
      Evaluation of potential mechanisms revealed reduced caveolin-1 and plasma
      membrane raft expression in EKO adipocytes. Increasing caveolin expression in EKO
      adipocytes increased fatty acid internalization. Our results establish a role for
      endogenous adipocyte apoE in VLDL-induced adipocyte lipogenesis by impacting both
      endocytic and lipoprotein lipase-mediated metabolic pathways. Reduced adipocyte
      apoE expression, for example that accompanying obesity, will suppress adipocyte
      acquisition of lipid from apoE-containing VLDL.

PMID- 19767396
TI  - Intimate partner violence: last year prevalence and association with socio
      economic factors among women in Madrid, Spain.
AB  - BACKGROUND: Intimate partner violence (IPV) is a public health problem with
      significant consequences on women's health. This study estimates the prevalence
      of intimate partner violence by type among Madrid's female population and
      assesses the association with socio-economic variables. METHODS: We conducted a
      cross-sectional study in 2004, 2136 women aged 18-70 years, living in the Madrid
      region with a partner or who had been in contact with an ex-partner in the
      previous year, were interviewed by telephone. The questionnaire used to measure
      past-year intimate partner violence, consisted of a Spanish translation of the
      psychological and sexual violence module of the French National Survey on
      Violence against Women, and the physical violence module of the Conflict Tactics
      Scale-1. To assess the association with socio-economic factors, logistic
      regression models were fitted. RESULTS: About 10.1% [confidence interval (CI) 8.9
      11.5] of the women had suffered some type of IPV in the previous year. 8.6% (CI
      7.4-9.8) experienced psychological violence, 2.4% (CI 1.8-3.1) physical violence
      and 1.1% (CI 0.68-1.6) sexual violence; the prevalence of psychological-only
      violence (non-physical/non-sexual) was 6.9% (CI 5.8-8.0). Factors associated with
      psychological-only violence were divorced or separated status and Group III
      (clerical workers; supervisors of manual workers) or V (unskilled manual workers)
      occupation. Unemployment and divorced or separated status were associated with
      physical violence. CONCLUSIONS: Spanish women in our study, experienced past year
      partner violence at a similar level as in other industrialized countries.
      Unemployment and low occupational status are associated with physical and
      psychological-only violence, respectively.

PMID- 19767395
TI  - Molecular determinants of MecA as a degradation tag for the ClpCP protease.
AB  - Regulated proteolysis by ATP-dependent proteases is universal in all living
      cells. In Bacillus subtilis, the degradation of the competence transcription
      factor ComK is mediated by a ternary complex involving the adaptor protein MecA
      and the ATP-dependent protease ClpCP. Here we demonstrate that a C-terminal, 98
      amino acid domain of MecA (residues 121-218) serves as a non-recycling,
      degradation tag and targets a variety of fusion proteins to the ClpCP protease
      for degradation. MecA-(121-218) facilitates productive oligomerization of ClpC,
      stimulates the ATPase activity of ClpC, and allows the activated ClpC complex to
      stably associate with ClpP. Importantly, the ClpCP protease undergoes dynamic
      cycles of assembly and disassembly, which are triggered by association with MecA
      and the degradation of MecA, respectively.

PMID- 19767397
TI  - Media running amok after school shooting in Winnenden, Germany!

PMID- 19767398
TI  - Increased sexually transmitted infection incidence in a low risk population:
      identifying the risk factors.
AB  - BACKGROUND: Between 1994 and 2006, the incidence of sexually transmitted
      infections (STIs) in Ireland has increased by over 300%. Recent literature would
      suggest that this figure is an underestimation of the true scale of infection.
      Our objective was to determine the risk factors associated with STI diagnosis in
      a population with a rapidly increasing STI incidence. METHODS: Using diagnostic,
      demographic and behavioural information from three STI clinics (January 1999 to
      December 2006), multivariable logistic regression models were used to identify
      risk factors associated with STI diagnosis. RESULTS: Age, smoking and
      inconsistent condom use are the dominant risk factors. Males aged 20-24 years and
      females aged <20 years being at greatest risk of STI acquisition. Having three or
      more partners was not associated with an elevated risk of STI diagnosis. At
      univariate level, homosexuals and bisexuals have a decreased risk of STI
      acquisition compared with heterosexuals. Rate of consistent condom use was low <
      or =13.3%. CONCLUSIONS: Age, condom use and number of sexual partners are
      important risk factors for STI diagnosis. Contrary to international STI
      literature, having multiple sexual partners does not increase STI incidence. Age
      specific behavioural interventions that target increased condom use may be
      effective in reducing STIs in Ireland. At policy level, a reduction in the
      taxation on condoms from 13.5 to 5% is needed to lower the prohibitive cost and
      increase their use.

PMID- 19767399
TI  - Adolescents' health-related dietary patterns by parental socio-economic position,
      the Nord-Trondelag Health Study (HUNT).
AB  - BACKGROUND: Nutrition is among the important determinants of diseases, and the
      social patterning of early eating habits may offer keys to prevention. We studied
      associations between selected indicators of adolescents' health-related dietary
      habits (daily intake of candy, soft drinks, fruit and vegetables) and parental
      socio-economic position (education, social class and income). METHODS: The
      material consisted of participants in the adolescent part (Young-HUNT) of the
      Nord-Trondelag Health Study during the period 1995-97, 8817 girls and boys aged
      13-19 years (89% of all students in junior high schools and high schools in a
      Norwegian county). Data on parental socio-economic position was available from
      the adult part of HUNT and Statistics Norway. Cross-sectional data analyses were
      performed using cross-tables and binary logistic regression. RESULTS: Of the
      indicators of socio-economic position used, the parent's educational level, in
      particular the mother's education, showed the highest impact on adolescents'
      health-related dietary habits. Girls with the least educated mothers had a
      prevalence odds ratio of 2.5 (1.8-3.3) for drinking soft drinks daily and 0.6
      (0.5-0.8) for eating vegetables daily as compared to girls with the most educated
      mothers. The corresponding numbers for boys were 1.9 (1.5-2.4) and 0.6 (0.5-0.8).
      Parental social class also showed gradients in adolescents' health-related
      dietary habits, but there was virtually no gradient by income. CONCLUSION: Higher
      levels of parental education, in particular the mother's education, are clearly
      associated with healthier dietary habits among adolescents. This social
      patterning should be recognized in public health interventions.

PMID- 19767400
TI  - Non-proteolytic HCN2 in the heart.

PMID- 19767402
TI  - LINGO-1, WNK1, and EGFR: a hypothesis.

PMID- 19767403
TI  - Non-quantal release of acetylcholine from parasympathetic nerve terminals in the
      right atrium of rats.
AB  - Acetylcholinesterase (AChE) inhibitors provoke typical cholinergic effects in the
      isolated right atrium of the rat due to the accumulation of acetylcholine (ACh).
      Our study was designed to show that in the absence of vagal impulse activity, ACh
      is released from the parasympathetic nerve fibres by means of non-quantal
      secretion. The conventional microelectrode technique was used to study changes in
      action potential (AP) configuration in the right atrium preparation of rats
      during application of AChE inhibitors. Staining with the lipophilic fluorescent
      dye FM1-43 was used to demonstrate the presence of endocytosis in cholinergic
      endings. The AChE inhibitors armin (10(7)-10(5)m) and neostigmine (10(7) to 5 x
      10(6)m) caused a reduction of AP duration and prolonged the cycle length. These
      effects were abolished by atropine and were therefore mediated by ACh accumulated
      in the myocardium during AChE inhibition. Putative block of impulse activity of
      the postganglionic neurons by tetrodotoxin (5 x 10(7)m) and blockade of
      ganglionic transmission by hexomethonium (2 x 10(4)m), as well as blockade of all
      forms of quantal release with Clostridium botulinum type A toxin (50 U ml(1)),
      did not alter the effects of armin. Experiments with FM1-43 dye confirmed the
      effective block of exocytosis by botulinum toxin. Selective inhibition of the
      choline uptake system using hemicholinium III (10(5)m), which blocks non-quantal
      release at the neuromuscular junction, suppressed the effects of AChE inhibitors.
      Thus, accumulation of ACh is likely to be caused by non-quantal release from
      cholinergic terminals. We propose that non-quantal release of ACh, shown
      previously at the neuromuscular junction, is present in cholinergic
      postganglionic fibres of the rat heart in addition to quantal release.

PMID- 19767404
TI  - Phlebolymphemeda: usually unrecognized, often poorly treated.
AB  - Phlebolymphedema is a condition of mixed venous and lymphatic insufficiency. It
      is usually not recognized and it is usually not treated. The lymphatic and venous
      systems are intimately interrelated. In the presence of venous hypertension,
      which is characteristic of most venous disorders, the increase in lymphatic flow
      becomes much greater than the lymph transport capacity. The diagnosis of
      phlebolymphedema is based on a detailed history and physical examination.
      Patients with phlebolymphedema have skin changes of venous insufficiency, which
      are easy to recognize. Treatment for chronic phlebolymphedema consists of
      treating the venous abnormality and watching regression of the lymphatic problem.

PMID- 19767405
TI  - Foam sclerotherapy: techniques and uses.
AB  - Sclerosant foam has been increasing in use in recent times. It has certain
      advantages over liquid sclerosants and is quite safe to use, despite the fact
      that there are adverse events that have been reported. The history of sclerosant
      foam goes back in time many years. Tessari developed the current method of
      creating sclerosant foam in 2001, and his technique has been modified. In our
      experience, the sclerosant foam has totally replaced other methods of treating
      venous insufficiency, and the results of treatment are superior to other methods.
      It is apparent that treatment of a variety of venous disorders can be
      accomplished using foam sclerotherapy. Our experience and that of others has
      shown that there are early advantages in the use of foam in the management of
      varicose veins compared with surgery and other methods.

PMID- 19767406
TI  - Anticoagulation strategies for venous thromboembolism.
AB  - Venous thromboembolism (VTE) continues to be a major source of morbidity and
      mortality in the United States with an estimated incidence of greater than 600
      000 clinically evident cases each year. It results in more than 200 000 deaths
      per year and is thought to be the number one cause of preventable in-hospital
      deaths. This review presents the history, pathophysiology, diagnostic
      considerations, and treatment options for VTE.

PMID- 19767407
TI  - Extracorporeal Membrane Oxygenation (ECMO). Introduction.

PMID- 19767408
TI  - Anticoagulation and coagulation management for ECMO.
AB  - Advances in extracorporeal membrane oxygenation (ECMO) management have helped to
      reduce complications compared with its inception but they remain high. The
      principal causes of mortality and morbidity are bleeding and thrombosis. The
      nonbiologic surface of an extracorporeal circuit provokes a massive inflammatory
      response leading to consumption and activation of procoagulant and anticoagulant
      components. The vast differences in neonatal and adult anticoagulation and
      transfusion requirements demands tremendous clinical knowledge to provide the
      best care. Increased use of thrombelastogram will complement other methods
      currently being used to improved care. Methods to recognize the level of thrombin
      formation at the bedside could help reduce neurologic complications. ECMO
      requires a multidisciplinary team approach to achieve the best outcomes.

PMID- 19767410
TI  - Biological evidence for the acute health effects of secondhand smoke exposure.
AB  - A vast number of studies on the unfavorable effects of secondhand smoke (SHS)
      exist within the international literature, the majority of which evaluate
      longitudinal epidemiological data. Although limited, the experimental studies
      that assess the acute and short-term effects of exposure to SHS are also
      increasing in number. They include cellular, animal, and human studies that
      indicate a number of pathophysiological mechanisms through which the deleterious
      effects of SHS may arise. This current review evaluates the existing biological
      evidence regarding the acute health effects of SHS exposure. Analyses on the
      inhaled toxicants and the carcinogenicity of SHS are included as well as in-depth
      discussions on the evidence for acute SHS-induced respiratory, cardiovascular,
      metabolic, endocrine and immune effects, and SHS-induced influences on oxygen
      delivery and exercise. The influence of the length of exposure and the duration
      of the observed effects is also described. Moreover, recent findings regarding
      the underlying pathophysiological mechanisms related to SHS are depicted so as to
      generate models that describe the SHS-induced effects on different systems within
      the human body. Based on the presented biological evidence, it is concluded that
      brief, acute, transient exposures to SHS may cause significant adverse effects on
      several systems of the human body and represent a significant and acute health
      hazard. Future research directions in this area include research on the
      concentrations of tobacco smoke constituents in the alveolar milieu following SHS
      exposure, individual susceptibility to SHS, as well as the effects of SHS on
      neurobehavioral activity, brain cell development, synaptic development, and
      function.

PMID- 19767409
TI  - Sustained hypoxia leads to the emergence of cells with enhanced growth,
      migratory, and promitogenic potentials within the distal pulmonary artery wall.
AB  - All forms of chronic pulmonary hypertension (PH) are characterized by structural
      remodeling of the pulmonary artery (PA) media, a process previously attributed
      solely to changes in the phenotype of resident smooth muscle cells (SMC).
      However, recent experimental evidence in both systemic and pulmonary circulations
      suggests that other cell types, including circulating and local progenitors,
      contribute significantly to this process. The goal of this study was to determine
      if hypoxia-induced remodeling of distal PA (dPA) media involves the emergence of
      cells with phenotypic and functional characteristics distinct from those of
      resident dPA SMC and fibroblasts. In vivo, in contrast to the phenotypically
      uniform SMC composition of dPA media in control calves, the remodeled dPA media
      of neonatal calves with severe hypoxia-induced PH comprised cells exhibiting a
      distinct phenotype, including the expression of hematopoetic (CD45),
      leukocytic/monocytic (CD11b, CD14), progenitor (cKit), and motility-associated
      (S100A4) cell markers. Consistent with these in vivo observations, primary cell
      cultures isolated from dPA media of hypertensive calves yielded not only
      differentiated SMC, but also smaller, morphologically rhomboidal (thus termed
      here "R") cells that transiently expressed CD11b, constitutively expressed the
      mesenchymal cell marker type I procollagen, expressed high mRNA levels of
      progenitor cell markers cKit, CD34, CD73, as well as for inflammatory mediators,
      IL-6 and MCP-1, and, with time in culture, gained expression of a myofibroblast
      marker, alpha-SM-actin. R cells exhibited highly augmented proliferative,
      migratory, invasive, and potent promitogenic capabilities, which were due, at
      least in part, to the production of PDGFs, SDF-1/CXCL12, and S100A4. These data
      suggest that the cellular mechanisms of dPA remodeling include the emergence of
      cells with phenotypic and functional characteristics markedly distinct from those
      of resident dPA cells.

PMID- 19767411
TI  - Deletion of caveolin-1 protects hyperoxia-induced apoptosis via survivin-mediated
      pathways.
AB  - Hyperoxia-induced lung injury is an established model that mimics human acute
      respiratory distress syndrome. Cell death is a prominent feature in lungs
      following prolonged hyperoxia. Caveolae are omega-shaped invaginations of the
      plasma membrane. Caveolin-1 (cav-1), a 22-kDa transmembrane scaffolding protein,
      is the principal structural component of caveolae. We have recently shown that
      deletion of cav-1 (cav-1-/-) protected against hyperoxia-induced cell death and
      lung injury both in vitro and in vivo; however, the mechanisms remain unclear.
      Survivin, a member of the inhibitor of apoptosis protein family, inhibits
      apoptosis in tumor cells. Although emerging evidence suggests that survivin is
      involved in wound healing, especially in vascular injuries, its role in hyperoxia
      induced lung injury has not been investigated. Our current data demonstrated that
      hyperoxia induced apoptosis via suppressing survivin expression. Deletion of cav
      1 abolished this suppression and subsequently protected against hyperoxia-induced
      apoptosis. Using "gain" and "loss" of function assays, we determined that
      survivin protected lung cells from hyperoxia-induced apoptosis via the inhibition
      of apoptosis executor caspase-3. Overexpression of survivin by deletion of cav-1
      was regulated by Egr-1. Egr-1 functioned as a negative regulator of survivin
      expression. Deletion of cav-1 upregulated survivin via decreased Egr-1 binding of
      the survivin promoter region. Together, this study illustrates the effect of
      hyperoxia on survivin expression and the role of survivin in hyperoxia-induced
      apoptosis. We also demonstrate that deletion of cav-1 protects hyperoxia-induced
      apoptosis via modulation of survivin expression.

PMID- 19767412
TI  - The unfolding stories of GPR30, a new membrane-bound estrogen receptor.
AB  - Steroid hormones such as estrogens are known to signal through ligand-regulated
      transcription factors of the nuclear receptor superfamily. In addition, they
      elicit rapid nongenomic responses from membrane-associated receptors. One of
      these receptors belongs to an entirely different family of proteins. The G
      protein-coupled and seven-transmembrane receptor, GPR30, is now widely recognized
      as an estrogen receptor (ER), hence its official new acronym GPER. It appears to
      mediate a wide range of responses to estrogen in a large variety of cell types.
      Its functions are clearly distinct from those of the classical nuclear ERs,
      although these pathways may overlap and interact in some cases. Here, we review
      the history of the discovery of this new ER, the evidence for the claim that it
      is an ER, its signal transduction, and its potential functions in physiology and
      disease.

PMID- 19767413
TI  - The epileptic human hippocampal cornu ammonis 2 region generates spontaneous
      interictal-like activity in vitro.
AB  - The dentate gyrus, the cornu ammonis 2 region and the subiculum of the human
      hippocampal formation are resistant to the cell loss associated with temporal
      lobe epilepsy. The subiculum, but not the dentate gyrus, generates interictal
      like activity in tissue slices from epileptic patients. In this study, we asked
      whether a similar population activity is generated in the cornu ammonis 2 region
      and examined the electrophysiological and neuroanatomical characteristics of
      human epileptic cornu ammonis 2 neurons that may be involved. Hippocampal slices
      were prepared from postoperative temporal lobe tissue derived from epileptic
      patients. Field potentials and multi-unit activity were recorded in vitro using
      multiple extracellular microelectrodes. Pyramidal cells were characterized in
      intra-cellular records and were filled with biocytin for subsequent anatomy.
      Fluorescent immunostaining was made on fixed tissue against the chloride-cation
      cotransporters sodium-potassium-chloride cotransporter-1 and potassium-chloride
      cotransporter-2. Light and electron microscopy were used to examine the
      parvalbumin-positive perisomatic inhibitory network. In 15 of 20 slices, the
      hippocampal cornu ammonis 2 region generated a spontaneous interictal-like
      activity, independently of population events in the subiculum. Most cornu ammonis
      2 pyramidal cells fired spontaneously. All cells fired single action potentials
      and burst firing was evoked in three cells. Spontaneous excitatory postsynaptic
      potentials were recorded in all cells, but hyperpolarizing inhibitory
      postsynaptic potentials were detected in only 27% of the cells. Two-thirds of
      cornu ammonis 2 neurons showed depolarizing responses during interictal-like
      events, while the others were inhibited, according to the current sink in the
      cell body layer. Two biocytin-filled cells both showed a pyramidal-like
      morphology with axons projecting to the cornu ammonis 2 and cornu ammonis 3
      regions. Expression of sodium-potassium-chloride cotransporter-1 and potassium
      chloride cotransporter-2 was reduced in some cells of the epileptic cornu ammonis
      2 region, but not to an extent corresponding to the proportion of cells in which
      hyperpolarizing postsynaptic potentials were absent. Numbers of parvalbumin
      positive inhibitory cells and axons were shown to be decreased in the epileptic
      tissue. Electron microscopy showed the preservation of somatic inhibitory input
      of cornu ammonis 2 cells, and confirmed the loss of parvalbumin from the
      interneurons rather than their death. An extra excitatory input (partly coming
      from sprouted mossy fibres) was demonstrated to innervate cornu ammonis 2 cell
      bodies. Our results show that the cornu ammonis 2 region of the sclerotic human
      hippocampus can generate an independent epileptiform activity. Inhibitory and
      excitatory signalling were functional but modified in epileptic cornu ammonis 2
      pyramidal cells. Overexcitation and the altered functional properties of
      perisomatic inhibitory network, rather than a modified chloride homeostasis, may
      account for the perturbed gamma-aminobutyric acid-ergic signalling and the
      generation of interictal-like activity in the human epileptic cornu ammonis 2
      region.

PMID- 19767414
TI  - When seeing outweighs feeling: a role for prefrontal cortex in passive control of
      negative affect in blindsight.
AB  - Affective neuroscience has been strongly influenced by the view that a 'feeling'
      is the perception of somatic changes and has consequently often neglected the
      neural mechanisms that underlie the integration of somatic and other information
      in affective experience. Here, we investigate affective processing by means of
      functional magnetic resonance imaging in nine cortically blind patients. In these
      patients, unilateral postgeniculate lesions prevent primary cortical visual
      processing in part of the visual field which, as a result, becomes subjectively
      blind. Residual subcortical processing of visual information, however, is assumed
      to occur in the entire visual field. As we have reported earlier, these patients
      show significant startle reflex potentiation when a threat-related visual
      stimulus is shown in their blind visual field. Critically, this was associated
      with an increase of brain activity in somatosensory-related areas, and an
      increase in experienced negative affect. Here, we investigated the patients'
      response when the visual stimulus was shown in the sighted visual field, that is,
      when it was visible and cortically processed. Despite the fact that startle
      reflex potentiation was similar in the blind and sighted visual field, patients
      reported significantly less negative affect during stimulation of the sighted
      visual field. In other words, when the visual stimulus was visible and received
      full cortical processing, the patients' phenomenal experience of affect did not
      closely reflect somatic changes. This decoupling of phenomenal affective
      experience and somatic changes was associated with an increase of activity in the
      left ventrolateral prefrontal cortex and a decrease of affect-related
      somatosensory activity. Moreover, patients who showed stronger left ventrolateral
      prefrontal cortex activity tended to show a stronger decrease of affect-related
      somatosensory activity. Our findings show that similar affective somatic changes
      can be associated with different phenomenal experiences of affect, depending on
      the depth of cortical processing. They are in line with a model in which the left
      ventrolateral prefrontal cortex is a relay station that integrates information
      about subcortically triggered somatic responses and information resulting from in
      depth cortical stimulus processing. Tentatively, we suggest that the observed
      decoupling of somatic responses and experienced affect, and the reduction of
      negative phenomenal experience, can be explained by a left ventrolateral
      prefrontal cortex-mediated inhibition of affect-related somatosensory activity.

PMID- 19767415
TI  - Prevalence of genetic muscle disease in Northern England: in-depth analysis of a
      muscle clinic population.
AB  - We have performed a detailed population study of patients with genetic muscle
      disease in the northern region of England. Our current clinic population
      comprises over 1100 patients in whom we have molecularly characterized 31
      separate muscle disease entities. Diagnostic clarity achieved through careful
      delineation of clinical features supported by histological, immunological and
      genetic analysis has allowed us to reach a definitive diagnosis in 75.7% of our
      patients. We have compared our case profile with that from Walton and Nattrass'
      seminal study from 1954, also of the northern region, together with data from
      other more recent studies from around the world. Point prevalence figures for
      each of the five major disease categories are comparable with those from other
      recent studies. Myotonic dystrophies are the most common, comprising 28.6% of our
      clinic population with a point prevalence of 10.6/100,000. Next most frequent are
      the dystrophinopathies and facioscapulohumeral muscular dystrophy making up 22.9%
      (8.46/100,000) and 10.7% (3.95/100,000) of the clinic population, respectively.
      Spinal muscular atrophy patients account for 5.1% or 1.87/100,000 patients. Limb
      girdle muscular dystrophy, which was described for the first time in the paper by
      Walton and Nattrass (1954) and comprised 17% of their clinic population,
      comprises 6.2% of our clinic population at a combined prevalence of 2.27/100,000.
      The clinic population included patients with 12 other muscle disorders. These
      disorders ranged from a point prevalence of 0.89/100 000 for the group of
      congenital muscular dystrophies to conditions with only two affected individuals
      in a population of three million. For the first time our study provides
      epidemiological information for X-linked Emery-Dreifuss muscular dystrophy and
      the collagen VI disorders. Each of the X-linked form of Emery-Dreifuss muscular
      dystrophy and Ullrich muscular dystrophy has a prevalence of 0.13/100,000, making
      both very rare. Bethlem myopathy was relatively more common with a prevalence of
      0.77/100,000. Overall our study provides comprehensive epidemiological
      information on individually rare inherited neuromuscular conditions in Northern
      England. Despite the deliberate exclusion of relatively common groups such as
      hereditary motor and sensory neuropathy (40/100,000) and mitochondrial disorders
      (9.2/100,000), the combined prevalence is 37.0/100,000, demonstrating that these
      disorders, taken as a group, encompass a significant proportion of patients with
      chronic disease. The study also illustrates the immense diagnostic progress since
      the first regional survey over 50 years ago by Walton and Nattrass.

PMID- 19767416
TI  - Relative contribution of sequence and structure features to the mRNA binding of
      Argonaute/EIF2C-miRNA complexes and the degradation of miRNA targets.
AB  - How miRNAs recognize their target sites is a puzzle that many experimental and
      computational studies aimed to solve. Several features, such as perfect pairing
      of the miRNA seed, additional pairing in the 3' region of the miRNA, relative
      position in the 3' UTR, and the A/U content of the environment of the putative
      site, have been found to be relevant. Here we have used a large number of
      previously published data sets to assess the power that various sequence and
      structure features have in distinguishing between putative sites that do and
      those that do not appear to be functional. We found that although different data
      sets give widely different answers when it comes to ranking the relative
      importance of these features, the sites inferred from most transcriptomics
      experiments, as well as from comparative genomics, appear similar at this level.
      This suggests that miRNA target sites have been selected in evolution on their
      ability to trigger mRNA degradation. To understand at what step in the miRNA
      induced response individual features play a role, we transfected human HEK293
      cells with miRNAs and analyzed the association of Argonaute/EIF2C-miRNA complexes
      with target mRNAs and the degradation of these messages. We found that structural
      features of the target site are only important for Argonaute/EIF2C binding, while
      sequence features such as the A/U content of the 3' UTR are important for mRNA
      degradation.

PMID- 19767417
TI  - The completion of the Mammalian Gene Collection (MGC).
AB  - Since its start, the Mammalian Gene Collection (MGC) has sought to provide at
      least one full-protein-coding sequence cDNA clone for every human and mouse gene
      with a RefSeq transcript, and at least 6200 rat genes. The MGC cloning effort
      initially relied on random expressed sequence tag screening of cDNA libraries.
      Here, we summarize our recent progress using directed RT-PCR cloning and DNA
      synthesis. The MGC now contains clones with the entire protein-coding sequence
      for 92% of human and 89% of mouse genes with curated RefSeq (NM-accession)
      transcripts, and for 97% of human and 96% of mouse genes with curated RefSeq
      transcripts that have one or more PubMed publications, in addition to clones for
      more than 6300 rat genes. These high-quality MGC clones and their sequences are
      accessible without restriction to researchers worldwide.

PMID- 19767418
TI  - Predictable dynamic program of timing of DNA replication in human cells.
AB  - The organization of mammalian DNA replication is poorly understood. We have
      produced high-resolution dynamic maps of the timing of replication in human
      erythroid, mesenchymal, and embryonic stem (ES) cells using TimEX, a method that
      relies on gaussian convolution of massive, highly redundant determinations of DNA
      copy-number variations during S phase to produce replication timing profiles. We
      first obtained timing maps of 3% of the genome using high-density oligonucleotide
      tiling arrays and then extended the TimEX method genome-wide using massively
      parallel sequencing. We show that in untransformed human cells, timing of
      replication is highly regulated and highly synchronous, and that many genomic
      segments are replicated in temporal transition regions devoid of initiation,
      where replication forks progress unidirectionally from origins that can be
      hundreds of kilobases away. Absence of initiation in one transition region is
      shown at the molecular level by single molecule analysis of replicated DNA
      (SMARD). Comparison of ES and erythroid cells replication patterns revealed that
      these cells replicate about 20% of their genome in different quarters of S phase.
      Importantly, we detected a strong inverse relationship between timing of
      replication and distance to the closest expressed gene. This relationship can be
      used to predict tissue-specific timing of replication profiles from expression
      data and genomic annotations. We also provide evidence that early origins of
      replication are preferentially located near highly expressed genes, that mid
      firing origins are located near moderately expressed genes, and that late-firing
      origins are located far from genes.

PMID- 19767419
TI  - In vivo detection of RNA-binding protein interactions with cognate RNA sequences
      by fluorescence resonance energy transfer.
AB  - Expression of the nascent RNA transcript is regulated by its interaction with a
      number of proteins. The misregulation of such interactions can often result in
      impaired cellular functions that can lead to cancer and a number of diseases.
      Thus, our understanding of RNA-protein interactions within the cellular context
      is essential for the development of novel diagnostic and therapeutic tools. While
      there are many in vitro methods that analyze RNA-protein interactions in vivo
      approaches are scarce. Here we established a method based on fluorescence
      resonance energy transfer (FRET), which we term RNA-binding mediated FRET (RB
      FRET), which determines RNA-protein interaction inside cells and tested it on
      hnRNP H protein binding to its cognate RNA. Using two different approaches, we
      provide evidence that RB-FRET is sensitive enough to detect specific RNA-protein
      interactions in the cell, providing a powerful tool to study spatial and temporal
      localization of specific RNA-protein complexes.

PMID- 19767420
TI  - Complex architecture and regulated expression of the Sox2ot locus during
      vertebrate development.
AB  - The Sox2 gene is a key regulator of pluripotency embedded within an intron of a
      long noncoding RNA (ncRNA), termed Sox2 overlapping transcript (Sox2ot), which is
      transcribed in the same orientation. However, this ncRNA remains uncharacterized.
      Here we show that Sox2ot has multiple transcription start sites associated with
      genomic features that indicate regulated expression, including highly conserved
      elements (HCEs) and chromatin marks characteristic of gene promoters. To identify
      biological processes in which Sox2ot may be involved, we analyzed its expression
      in several developmental systems, compared to expression of Sox2. We show that
      Sox2ot is a stable transcript expressed in mouse embryonic stem cells, which,
      like Sox2, is down-regulated upon induction of embryoid body (EB)
      differentiation. However, in contrast to Sox2, Sox2ot is up-regulated during EB
      mesoderm-lineage differentiation. In adult mouse, Sox2ot isoforms were detected
      in tissues where Sox2 is expressed, as well as in different tissues, supporting
      independent regulation of expression of the ncRNA. Sox2dot, an isoform of Sox2ot
      transcribed from a distal HCE located >500 kb upstream of Sox2, was detected
      exclusively in the mouse brain, with enrichment in regions of adult neurogenesis.
      In addition, Sox2ot isoforms are transcribed from HCEs upstream of Sox2 in other
      vertebrates, including in several regions of the human brain. We also show that
      Sox2ot is dynamically regulated during chicken and zebrafish embryogenesis,
      consistently associated with central nervous system structures. These
      observations provide insight into the structure and regulation of the Sox2ot
      gene, and suggest conserved roles for Sox2ot orthologs during vertebrate
      development.

PMID- 19767421
TI  - Real-time fluorescence detection of exoribonucleases.
AB  - The identification of RNases or RNase effectors is a continuous challenge,
      particularly given the current importance of RNAs in the control of genome
      expression. Here, we show that a fluorogenic RNA-DNA hybrid is a powerful tool
      for a real-time fluorescence detection and assay of exoribonucleases (RT-FeDEx).
      This RT-FeDEx assay provides a new strategy for the isolation, purification, and
      assay of known and unknown exoribonucleases.

PMID- 19767422
TI  - Role of the transcriptional regulator RamB (Rv0465c) in the control of the
      glyoxylate cycle in Mycobacterium tuberculosis.
AB  - Mycobacterium tuberculosis generally is assumed to depend on lipids as a major
      carbon and energy source when persisting within the host. The utilization of
      fatty acids requires a functional glyoxylate cycle with the key enzymes
      isocitrate lyase (Icl) and malate synthase. The open reading frame Rv0465c of M.
      tuberculosis H37Rv encodes a protein with significant sequence similarity to the
      transcriptional regulator RamB, which in Corynebacterium glutamicum controls the
      expression of several genes involved in acetate metabolism, i.e., those encoding
      enzymes of acetate activation and the glyoxylate cycle. We show here that the M.
      tuberculosis Rv0465c protein can functionally complement RamB in C. glutamicum
      and that it binds to the promoter regions of M. tuberculosis icl1 and Rv0465c.
      Construction and subsequent transcriptional and enzymatic analysis of a defined
      Rv0465c deletion mutant in M. tuberculosis revealed that the Rv0465c protein, now
      designated RamB, represses icl1 expression during growth with glucose and
      negatively autoregulates the expression of its own operon. Whole-genome
      microarray analysis of the M. tuberculosis ramB (ramB(MT)) mutant and the wild
      type furthermore showed that apart from icl1 and the ramB(MT) operon, the
      expression of all other M. tuberculosis genes involved in acetate metabolism
      remain unchanged in the mutant. Thus, RamB(MT) has a more specific regulatory
      function as RamB from C. glutamicum and is confined to expression control of icl1
      and the ramB(MT) operon.

PMID- 19767423
TI  - Structural and genetic basis for the serological differentiation of Pasteurella
      multocida Heddleston serotypes 2 and 5.
AB  - Pasteurella multocida is classified into 16 serotypes according to the Heddleston
      typing scheme. As part of a comprehensive study to define the structural and
      genetic basis of this scheme, we have determined the structure of the
      lipopolysaccharide (LPS) produced by P. multocida strains M1404 (B:2) and P1702
      (E:5), the type strains for serotypes 2 and 5, respectively. The only difference
      between the LPS structures made by these two strains was the absence of a
      phosphoethanolamine (PEtn) moiety at the 3 position of the second heptose (Hep
      II) in M1404. Analysis of the lpt-3 gene, required for the addition of this PEtn
      residue, revealed that the gene was intact in P1702 but contained a nonsense
      mutation in M1404. Expression of an intact copy of lpt-3 in M1404 resulted in the
      attachment of a PEtn residue to the 3 position of the Hep II residue, generating
      an LPS structure identical to that produced by P1702. We identified and
      characterized each of the glycosyltransferase genes required for assembly of the
      serotype 2 and 5 LPS outer core. Monoclonal antibodies raised against serotype 2
      LPS recognized the serotype 2/5-specific outer core LPS structure, but
      recognition of this structure was inhibited by the PEtn residue on Hep II. These
      data indicate that the serological classification of strains into Heddleston
      serotypes 2 and 5 is dependent on the presence or absence of PEtn on Hep II.

PMID- 19767424
TI  - Tryptophan inhibits Proteus vulgaris TnaC leader peptide elongation, activating
      tna operon expression.
AB  - Expression of the tna operon of Escherichia coli and of Proteus vulgaris is
      induced by L-tryptophan. In E. coli, tryptophan action is dependent on the
      presence of several critical residues (underlined) in the newly synthesized TnaC
      leader peptide, WFNIDXXL/IXXXXP. These residues are conserved in TnaC of P.
      vulgaris and of other bacterial species. TnaC of P. vulgaris has one additional
      feature, distinguishing it from TnaC of E. coli; it contains two C-terminal
      lysine residues following the conserved proline residue. In the present study, we
      investigated L-tryptophan induction of the P. vulgaris tna operon, transferred on
      a plasmid into E. coli. Induction was shown to be L-tryptophan dependent;
      however, the range of induction was less than that observed for the E. coli tna
      operon. We compared the genetic organization of both operons and predicted
      similar folding patterns for their respective leader mRNA segments. However,
      additional analyses revealed that L-tryptophan action in the P. vulgaris tna
      operon involves inhibition of TnaC elongation, following addition of proline,
      rather than inhibition of leader peptide termination. Our findings also establish
      that the conserved residues in TnaC of P. vulgaris are essential for L-tryptophan
      induction, and for inhibition of peptide elongation. TnaC synthesis is thus an
      excellent model system for studies of regulation of both peptide termination and
      peptide elongation, and for studies of ribosome recognition of the features of a
      nascent peptide.

PMID- 19767425
TI  - Zinc-independent folate biosynthesis: genetic, biochemical, and structural
      investigations reveal new metal dependence for GTP cyclohydrolase IB.
AB  - GTP cyclohydrolase I (GCYH-I) is an essential Zn(2+)-dependent enzyme that
      catalyzes the first step of the de novo folate biosynthetic pathway in bacteria
      and plants, the 7-deazapurine biosynthetic pathway in Bacteria and Archaea, and
      the biopterin pathway in mammals. We recently reported the discovery of a new
      prokaryotic-specific GCYH-I (GCYH-IB) that displays no sequence identity to the
      canonical enzyme and is present in approximately 25% of bacteria, the majority of
      which lack the canonical GCYH-I (renamed GCYH-IA). Genomic and genetic analyses
      indicate that in those organisms possessing both enzymes, e.g., Bacillus
      subtilis, GCYH-IA and -IB are functionally redundant, but differentially
      expressed. Whereas GCYH-IA is constitutively expressed, GCYH-IB is expressed only
      under Zn(2+)-limiting conditions. These observations are consistent with the
      hypothesis that GCYH-IB functions to allow folate biosynthesis during Zn(2+)
      starvation. Here, we present biochemical and structural data showing that
      bacterial GCYH-IB, like GCYH-IA, belongs to the tunneling-fold (T-fold)
      superfamily. However, the GCYH-IA and -IB enzymes exhibit significant differences
      in global structure and active-site architecture. While GCYH-IA is a unimodular,
      homodecameric, Zn(2+)-dependent enzyme, GCYH-IB is a bimodular, homotetrameric
      enzyme activated by a variety of divalent cations. The structure of GCYH-IB and
      the broad metal dependence exhibited by this enzyme further underscore the
      mechanistic plasticity that is emerging for the T-fold superfamily. Notably,
      while humans possess the canonical GCYH-IA enzyme, many clinically important
      human pathogens possess only the GCYH-IB enzyme, suggesting that this enzyme is a
      potential new molecular target for antibacterial development.

PMID- 19767426
TI  - A 5' leader sequence regulates expression of methanosarcinal CO
      dehydrogenase/acetyl coenzyme A synthase.
AB  - In vivo expression of CO dehydrogenase/acetyl coenzyme A synthase in
      Methanosarcina spp. is coordinately regulated in response to substrate by at
      least two mechanisms: differential transcription initiation and early elongation
      termination near the 3' end of a 371-bp leader sequence. This is the first report
      of regulation of transcription elongation in the Archaea.

PMID- 19767427
TI  - The dlt operon of Bacillus cereus is required for resistance to cationic
      antimicrobial peptides and for virulence in insects.
AB  - The dlt operon encodes proteins that alanylate teichoic acids, the major
      components of cell walls of gram-positive bacteria. This generates a net positive
      charge on bacterial cell walls, repulsing positively charged molecules and
      conferring resistance to animal and human cationic antimicrobial peptides (AMPs)
      in gram-positive pathogenic bacteria. AMPs damage the bacterial membrane and are
      the most effective components of the humoral immune response against bacteria. We
      investigated the role of the dlt operon in insect virulence by inactivating this
      operon in Bacillus cereus, which is both an opportunistic human pathogen and an
      insect pathogen. The Delta dlt(Bc) mutant displayed several morphological
      alterations but grew at a rate similar to that for the wild-type strain. This
      mutant was less resistant to protamine and several bacterial cationic AMPs, such
      as nisin, polymyxin B, and colistin, in vitro. It was also less resistant to
      molecules from the insect humoral immune system, lysozyme, and cationic AMP
      cecropin B from Spodoptera frugiperda. Delta dlt(Bc) was as pathogenic as the
      wild-type strain in oral infections of Galleria mellonella but much less virulent
      when injected into the hemocoels of G. mellonella and Spodoptera littoralis. We
      detected the dlt operon in three gram-negative genera: Erwinia (Erwinia
      carotovora), Bordetella (Bordetella pertussis, Bordetella parapertussis, and
      Bordetella bronchiseptica), and Photorhabdus (the entomopathogenic bacterium
      Photorhabdus luminescens TT01, the dlt operon of which did not restore cationic
      AMP resistance in Delta dlt(Bc)). We suggest that the dlt operon protects B.
      cereus against insect humoral immune mediators, including hemolymph cationic
      AMPs, and may be critical for the establishment of lethal septicemia in insects
      and in nosocomial infections in humans.

PMID- 19767428
TI  - Thioredoxin 1 participates in the activity of the Salmonella enterica serovar
      Typhimurium pathogenicity island 2 type III secretion system.
AB  - The facultative intracellular pathogen Salmonella enterica serovar Typhimurium
      relies on its Salmonella pathogenicity island 2 (SPI2) type III secretion system
      (T3SS) for intracellular replication and virulence. We report that the
      oxidoreductase thioredoxin 1 (TrxA) and SPI2 are coinduced for expression under
      in vitro conditions that mimic an intravacuolar environment, that TrxA is needed
      for proper SPI2 activity under these conditions, and that TrxA is indispensable
      for SPI2 activity in both phagocytic and epithelial cells. Infection experiments
      in mice demonstrated that SPI2 strongly contributed to virulence in a TrxA
      proficient background whereas SPI2 did not affect virulence in a trxA mutant.
      Complementation analyses using wild-type trxA or a genetically engineered trxA
      coding for noncatalytic TrxA showed that the catalytic activity of TrxA is
      essential for SPI2 activity in phagocytic cells whereas a noncatalytic variant of
      TrxA partially sustained SPI2 activity in epithelial cells and virulence in mice.
      These results show that TrxA is needed for the intracellular induction of SPI2
      and provide new insights into the functional integration between catalytic and
      noncatalytic activities of TrxA and a bacterial T3SS in different settings of
      intracellular infections.

PMID- 19767429
TI  - A protein important for antimicrobial peptide resistance, YdeI/OmdA, is in the
      periplasm and interacts with OmpD/NmpC.
AB  - Antimicrobial peptides (AMPs) kill or prevent the growth of microbes. AMPs are
      made by virtually all single and multicellular organisms and are encountered by
      bacteria in diverse environments, including within a host. Bacteria use sensor
      kinase systems to respond to AMPs or damage caused by AMPs. Salmonella enterica
      deploys at least three different sensor-kinase systems to modify gene expression
      in the presence of AMPs: PhoP-PhoQ, PmrA-PmrB, and RcsB-RcsC-RcsD. The ydeI gene
      is regulated by the RcsB-RcsC-RcsD pathway and encodes a 14-kDa predicted
      oligosaccharide/oligonucleotide binding-fold (OB-fold) protein important for
      polymyxin B resistance in broth and also for virulence in mice. We report here
      that ydeI is additionally regulated by the PhoP-PhoQ and PmrA-PmrB sensor-kinase
      systems, which confer resistance to cationic AMPs by modifying lipopolysaccharide
      (LPS). ydeI, however, is not important for known LPS modifications. Two
      independent biochemical methods found that YdeI copurifies with OmpD/NmpC, a
      member of the trimeric beta-barrel outer membrane general porin family. Genetic
      analysis indicates that ompD contributes to polymyxin B resistance, and both ydeI
      and ompD are important for resistance to cathelicidin antimicrobial peptide, a
      mouse AMP produced by multiple cell types and expressed in the gut. YdeI
      localizes to the periplasm, where it could interact with OmpD. A second predicted
      periplasmic OB-fold protein, YgiW, and OmpF, another general porin, also
      contribute to polymyxin B resistance. Collectively, the data suggest that
      periplasmic OB-fold proteins can interact with porins to increase bacterial
      resistance to AMPs.

PMID- 19767430
TI  - SigmaX is involved in controlling Bacillus subtilis biofilm architecture through
      the AbrB homologue Abh.
AB  - A characteristic feature of biofilm formation is the production of a protective
      extracellular polymeric matrix. In the gram-positive bacterium Bacillus subtilis,
      the biofilm matrix is synthesized by the products of the epsABCDEFGHIJKLMNO
      operon (hereafter called the eps operon) and yqxM-sipW-tasA loci. Transcription
      from these operons is repressed by two key regulators, AbrB and SinR. Relief of
      inhibition is necessary to allow biofilm formation to proceed. Here we present
      data indicating that Abh, a sequence and structural homologue of AbrB, regulates
      biofilm architecture by B. subtilis when colony morphology and pellicle formation
      are assessed. Data indicating that abh expression is dependent on the
      environmental signals that stimulate the activity of the extracytoplasmic
      function sigma-factor sigma(X) are shown. We demonstrate that expression of slrR,
      the proposed activator of yqxM transcription, is positively controlled by Abh.
      Furthermore, Abh is shown to activate transcription from the promoter of the eps
      operon through its control of SlrR. These findings add to the increasingly
      complex transcriptional network that controls biofilm formation by B. subtilis.

PMID- 19767431
TI  - Physiology and posttranscriptional regulation of methanol:coenzyme M
      methyltransferase isozymes in Methanosarcina acetivorans C2A.
AB  - Methanosarcina species possess three operons (mtaCB1, mtaCB2, and mtaCB3)
      encoding methanol-specific methyltransferase 1 (MT1) isozymes and two genes
      (mtaA1 and mtaA2) with the potential to encode a methanol-specific
      methyltransferase 2 (MT2). Previous genetic studies showed that these genes are
      differentially regulated and encode enzymes with distinct levels of
      methyltransferase activity. Here, the effects of promoter strength on growth and
      on the rate of methane production were examined by constructing strains in which
      the mtaCB promoters were exchanged. When expressed from the strong PmtaC1 or
      PmtaC2 promoter, each of the MtaC and MtaB proteins supported growth and methane
      production at wild-type levels. In contrast, all mtaCB operons exhibited poorer
      growth and lower rates of methane production when PmtaC3 controlled their
      expression. Thus, previously observed phenotypic differences can be attributed
      largely to differences in promoter activity. Strains carrying various
      combinations of mtaC, mtaB, and mtaA expressed from the strong, tetracycline
      regulated PmcrB(tetO1) promoter exhibited similar growth characteristics on
      methanol, showing that all combinations of MtaC, MtaB, and MtaA can form
      functional MT1/MT2 complexes. However, an in vitro assay of coupled MT1/MT2
      activity showed significant variation between the strains. Surprisingly, these
      variations in activity correlated with differences in protein abundance, despite
      the fact that all the encoding genes were expressed from the same promoter.
      Quantitative reverse transcriptase PCR and reporter gene fusion data suggest that
      the mtaCBA transcripts show different stabilities, which are strongly influenced
      by the growth substrate.

PMID- 19767432
TI  - Functional analysis of the Helicobacter pylori flagellar switch proteins.
AB  - Helicobacter pylori uses flagellum-mediated chemotaxis to promote infection.
      Bacterial flagella change rotational direction by changing the state of the
      flagellar motor via a subcomplex referred to as the switch. Intriguingly, the H.
      pylori genome encodes four switch complex proteins, FliM, FliN, FliY, and FliG,
      instead of the more typical three of Escherichia coli or Bacillus subtilis. Our
      goal was to examine whether and how all four switch proteins participate in
      flagellation. Previous work determined that FliG was required for flagellation,
      and we extend those findings to show that all four switch proteins are necessary
      for normal numbers of flagellated cells. Furthermore, while fliY and fliN are
      partially redundant with each other, both are needed for wild-type levels of
      flagellation. We also report the isolation of an H. pylori strain containing an
      R54C substitution in fliM, resulting in bacteria that swim constantly and do not
      change direction. Along with data demonstrating that CheY-phosphate interacts
      with FliM, these findings suggest that FliM functions in H. pylori much as it
      does in other organisms.

PMID- 19767433
TI  - Complete genome sequence of the ethanol producer Zymomonas mobilis NCIMB 11163.
AB  - Zymomonas mobilis is an ethanol-producing alphaproteobacterium currently
      considered a major candidate organism for bioethanol production. Here we report
      the finished and annotated genome sequence of Z. mobilis subsp. mobilis strain
      NCIMB 11163, a British ale-infecting isolate. This is the first Z. mobilis strain
      whose genome, chromosomal and plasmid, is presented in its entirety.

PMID- 19767434
TI  - A novel regulatory protein involved in motility of Vibrio cholerae.
AB  - The facultative pathogen Vibrio cholerae is the causative agent of the human
      intestinal disease cholera. Both motility and chemotaxis of V. cholerae have been
      shown to contribute to the virulence and spread of cholera. The flagellar gene
      operons are organized into a hierarchy composed of four classes (I to IV) based
      on their temporal expression patterns. Some regulatory elements involved in
      flagellar gene expression have been elucidated, but regulation is complex and
      flagellar biogenesis in V. cholerae is not completely understood. In this study,
      we determined that the virulence defect of a V. cholerae cheW1 deletion mutant
      was due to polar effects on the downstream open reading frame VC2058 (flrD).
      Expression of flrD in trans restored the virulence defect of the cheW1 deletion
      mutant, and deletion of flrD resulted in a V. cholerae strain attenuated for
      virulence, as determined by using the infant mouse intestinal colonization model.
      The flrD mutant strain exhibited decreased transcription of class III and IV
      flagellar genes and reduced motility. Transcription of the flrD promoter, which
      lies within the coding sequence of cheW1, is independent of the flagellar
      transcriptional activators FlrA and RpoN, which activate class II genes,
      indicating that flrD does not fit into any of the four flagellar gene classes.
      Genetic epistasis studies revealed that the two-component system FlrBC, which is
      required for class III and IV flagellar gene transcription, acts downstream of
      flrD. We hypothesize that the inner membrane protein FlrD interacts with the
      cytoplasmic FlrBC complex to activate class III and IV gene transcription.

PMID- 19767435
TI  - The beta-barrel outer membrane protein assembly complex of Neisseria
      meningitidis.
AB  - The evolutionarily conserved protein Omp85 is required for outer membrane protein
      (OMP) assembly in gram-negative bacteria and in mitochondria. Its Escherichia
      coli homolog, designated BamA, functions with four accessory lipoproteins, BamB,
      BamC, BamD, and BamE, together forming the beta-barrel assembly machinery (Bam).
      Here, we addressed the composition of this machinery and the function of its
      components in Neisseria meningitidis, a model organism for outer membrane
      biogenesis studies. Analysis of genome sequences revealed homologs of BamC, BamD
      (previously described as ComL), and BamE and a second BamE homolog, Mlp. No
      homolog of BamB was found. As in E. coli, ComL/BamD appeared essential for
      viability and for OMP assembly, and it could not be replaced by its E. coli
      homolog. BamE was not essential but was found to contribute to the efficiency of
      OMP assembly and to the maintenance of OM integrity. A bamC mutant showed only
      marginal OMP assembly defects, but the impossibility of creating a bamC bamE
      double mutant further indicated the function of BamC in OMP assembly. An mlp
      mutant was unaffected in OMP assembly. The results of copurification assays
      demonstrated the association of BamC, ComL, and BamE with Omp85. Semi-native gel
      electrophoresis identified the RmpM protein as an additional component of the
      Omp85 complex, which was confirmed in copurification assays. RmpM was not
      required for OMP folding but stabilized OMP complexes. Thus, the Bam complex in
      N. meningitidis consists of Omp85/BamA plus RmpM, BamC, ComL/BamD, and BamE, of
      which ComL/BamD and BamE appear to be the most important accessory components for
      OMP assembly.

PMID- 19767436
TI  - Complete genome sequence of Lactobacillus johnsonii FI9785, a competitive
      exclusion agent against pathogens in poultry.
AB  - Lactobacillus johnsonii is a member of the acidophilus group of lactobacilli.
      Because of their probiotic properties, including attachment to epithelial cells,
      immunomodulation, and competitive exclusion of pathogens, representatives of this
      group are being intensively studied. Here we report the complete annotated genome
      sequence of Lactobacillus johnsonii FI9785, a strain which prevents the
      colonization of specific-pathogen-free chicks by Clostridium perfringens.

PMID- 19767438
TI  - Complete genome sequence of Robiginitalea biformata HTCC2501.
AB  - Robiginitalea biformata HTCC2501, isolated from the Sargasso Sea by dilution-to
      extinction culturing, has been known as an aerobic chemoheterotroph with
      carotenoid pigments and dimorphic growth phases. Here, we announce the complete
      sequence of the R. biformata HTCC2501 genome, which contains genes for carotenoid
      biosynthesis and several macromolecule-degrading enzymes.

PMID- 19767437
TI  - Plasmid r1 conjugative DNA processing is regulated at the coupling protein
      interface.
AB  - Selective substrate uptake controls initiation of macromolecular secretion by
      type IV secretion systems in gram-negative bacteria. Type IV coupling proteins
      (T4CPs) are essential, but the molecular mechanisms governing substrate entry to
      the translocation pathway remain obscure. We report a biochemical approach to
      reconstitute a regulatory interface between the plasmid R1 T4CP and the
      nucleoprotein relaxosome dedicated to the initiation stage of plasmid DNA
      processing and substrate presentation. The predicted cytosolic domain of T4CP
      TraD was purified in a predominantly monomeric form, and potential regulatory
      effects of this protein on catalytic activities exhibited by the relaxosome
      during transfer initiation were analyzed in vitro. TraDDeltaN130 stimulated the
      TraI DNA transesterase activity apparently via interactions on both the protein
      and the DNA levels. TraM, a protein interaction partner of TraD, also increased
      DNA transesterase activity in vitro. The mechanism may involve altered DNA
      conformation as TraM induced underwinding of oriT plasmid DNA in vivo (DeltaL(k)
      = -4). Permanganate mapping of the positions of duplex melting due to relaxosome
      assembly with TraDDeltaN130 on supercoiled DNA in vitro confirmed localized
      unwinding at nic but ruled out formation of an open complex compatible with
      initiation of the TraI helicase activity. These data link relaxosome regulation
      to the T4CP and support the model that a committed step in the initiation of DNA
      export requires activation of TraI helicase loading or catalysis.

PMID- 19767439
TI  - Protein and DNA effectors control the TraI conjugative helicase of plasmid R1.
AB  - The mechanisms controlling progression of conjugative DNA processing from a
      preinitiation stage of specific plasmid strand cleavage at the transfer origin to
      a stage competent for unwinding the DNA strand destined for transfer remain
      obscure. Linear heteroduplex substrates containing double-stranded DNA binding
      sites for plasmid R1 relaxosome proteins and various regions of open duplex for
      TraI helicase loading were constructed to model putative intermediate structures
      in the initiation pathway. The activity of TraI was compared in steady-state
      multiple turnover experiments that measured the net production of unwound DNA as
      well as transesterase-catalyzed cleavage at nic. Helicase efficiency was enhanced
      by the relaxosome components TraM and integration host factor. The magnitude of
      stimulation depended on the proximity of the specific protein binding sites to
      the position of open DNA. The cytoplasmic domain of the R1 coupling protein,
      TraDDeltaN130, stimulated helicase efficiency on all substrates in a manner
      consistent with cooperative interaction and sequence-independent DNA binding.
      Variation in the position of duplex opening also revealed an unsuspected
      autoinhibition of the unwinding reaction catalyzed by full-length TraI. The
      activity reduction was sequence dependent and was not observed with a truncated
      helicase, TraIDeltaN308, lacking the site-specific DNA binding transesterase
      domain. Given that transesterase and helicase domains are physically tethered in
      the wild-type protein, this observation suggests that an intramolecular switch
      controls helicase activation. The data support a model where protein-protein and
      DNA ligand interactions at the coupling protein interface coordinate the
      transition initiating production and uptake of the nucleoprotein secretion
      substrate.

PMID- 19767440
TI  - Functional characterization of SsaE, a novel chaperone protein of the type III
      secretion system encoded by Salmonella pathogenicity island 2.
AB  - The type III secretion system (T3SS) encoded by Salmonella pathogenicity island 2
      (SPI-2) is involved in systemic infection and intracellular replication of
      Salmonella enterica serovar Typhimurium. In this study, we investigated the
      function of SsaE, a small cytoplasmic protein encoded within the SPI-2 locus,
      which shows structural similarity to the T3SS class V chaperones. An S. enterica
      serovar Typhimurium ssaE mutant failed to secrete SPI-2 translocator SseB and SPI
      2-dependent effector PipB proteins. Coimmunoprecipitation and mass spectrometry
      analyses using an SsaE-FLAG fusion protein indicated that SsaE interacts with
      SseB and a putative T3SS-associated ATPase, SsaN. A series of deleted and point
      mutated SsaE-FLAG fusion proteins revealed that the C-terminal coiled-coil domain
      of SsaE is critical for protein-protein interactions. Although SseA was reported
      to be a chaperone for SseB and to be required for its secretion and stability in
      the bacterial cytoplasm, an sseA deletion mutant was able to secrete the SseB in
      vitro when plasmid-derived SseB was overexpressed. In contrast, ssaE mutant
      strains could not transport SseB extracellularly under the same assay conditions.
      In addition, an ssaE(I55G) point-mutated strain that expresses the SsaE
      derivative lacking the ability to form a C-terminal coiled-coil structure showed
      attenuated virulence comparable to that of an SPI-2 T3SS null mutant, suggesting
      that the coiled-coil interaction of SsaE is absolutely essential for the
      functional SPI-2 T3SS and for Salmonella virulence. Based on these findings, we
      propose that SsaE recognizes translocator SseB and controls its secretion via SPI
      2 type III secretion machinery.

PMID- 19767441
TI  - The response regulator SprE (RssB) modulates polyadenylation and mRNA stability
      in Escherichia coli.
AB  - In Escherichia coli, the adaptor protein SprE (RssB) controls the stability of
      the alternate sigma factor RpoS (sigma(38) and sigma(S)). When nutrients are
      abundant, SprE binds RpoS and delivers it to ClpXP for degradation, but when
      carbon sources are depleted, this process is inhibited. It also has been noted
      that overproduction of SprE is toxic. Here we show that null mutations in pcnB,
      encoding poly(A) polymerase I (PAP I), and in hfq, encoding the RNA chaperone
      Hfq, suppress this toxicity. Since PAP I, in conjunction with Hfq, is responsible
      for targeting RNAs, including mRNAs, for degradation by adding poly(A) tails onto
      their 3' ends, these data indicate that SprE helps modulate the polyadenylation
      pathway in E. coli. Indeed, in exponentially growing cells, sprE deletion mutants
      exhibit significantly reduced levels of polyadenylation and increased stability
      of specific mRNAs, similar to what is observed in a PAP I-deficient strain. In
      stationary phase, we show that SprE changes the intracellular localization of PAP
      I. Taken together, we propose that SprE plays a multifunctional role in
      controlling the transcriptome, regulating what is made via its effects on RpoS,
      and modulating what is degraded via its effects on polyadenylation and turnover
      of specific mRNAs.

PMID- 19767442
TI  - Differential contribution of the mitochondrial respiratory chain complexes to
      reactive oxygen species production by redox cycling agents implicated in
      parkinsonism.
AB  - Exposure to environmental pesticides can cause significant brain damage and has
      been linked with an increased risk of developing neurodegenerative disorders,
      including Parkinson's disease. Bipyridyl herbicides, such as paraquat (PQ),
      diquat (DQ), and benzyl viologen (BV), are redox cycling agents known to exert
      cellular damage through the production of reactive oxygen species (ROS). We
      examined the involvement of the mitochondrial respiratory chain in ROS production
      by bipyridyl herbicides. In isolated rat brain mitochondria, H2O2 production
      occurred with the following order of potency: BV > DQ > PQ in accordance with
      their measured ability to redox cycle. H2O2 production was significantly
      attenuated in all cases by antimycin A, an inhibitor of complex III.
      Interestingly, at micromolar (< or = 300 microM) concentrations, PQ-induced H2O2
      production was unaffected by complex I inhibition via rotenone, whereas DQ
      induced H2O2 production was equally attenuated by inhibition of complex I or III.
      Moreover, complex I inhibition decreased BV-induced H2O2 production to a greater
      extent than with PQ or DQ. These data suggest that multiple sites within the
      respiratory chain contribute to H2O2 production by redox cycling bipyridyl
      herbicides. In primary midbrain cultures, H2O2 differed slightly with the
      following order of potency: DQ > BV > PQ. In this model, inhibition of complex
      III resulted in roughly equivalent inhibition of H2O2 production with all three
      compounds. These data identify a novel role for complex III dependence of
      mitochondrial ROS production by redox cycling herbicides, while emphasizing the
      importance of identifying mitochondrial mechanisms by which environmental agents
      generate oxidative stress contributing to parkinsonism.

PMID- 19767443
TI  - Dynamic nature of alterations in the endocrine system of fathead minnows exposed
      to the fungicide prochloraz.
AB  - The vertebrate hypothalamic-pituitary-gonadal (HPG) axis is controlled through
      various feedback mechanisms that maintain a dynamic homeostasis in the face of
      changing environmental conditions, including exposure to chemicals. We assessed
      the effects of prochloraz on HPG axis function in adult fathead minnows
      (Pimephales promelas) at multiple sampling times during 8-day exposure and 8-day
      depuration/recovery phases. Consistent with one mechanism of action of
      prochloraz, inhibition of cytochrome P450 (CYP) 19 aromatase activity, the
      fungicide depressed ex vivo ovarian production and plasma concentrations of
      17beta-estradiol (E2) in female fish. At a prochloraz water concentration of 30
      microg/l, inhibitory effects on E2 production were transitory and did not persist
      during the 8-day exposure phase. At 300 microg/l prochloraz, inhibition of E2
      production was evident throughout the 8-day exposure but steroid titers recovered
      within 1 day of cessation of exposure. Compensation or recovery of steroid
      production in prochloraz-exposed females was accompanied by upregulation of
      several ovarian genes associated with steroidogenesis, including cyp19a1a, cyp17
      (hydroxylase/lyase), cyp11a (cholesterol side-chain cleavage), and follicle
      stimulating hormone receptor. In male fathead minnows, the 8-day prochloraz
      exposure decreased testosterone (T) production, possibly through inhibition of
      CYP17. However, as for E2 in females, ex vivo testicular production and plasma
      concentrations of T recovered within 1 day of stopping exposure. Steroidogenic
      genes upregulated in testis included cyp17 and cyp11a. These studies demonstrate
      the adaptability of the HPG axis to chemical stress and highlight the need to
      consider the dynamic nature of the system when developing approaches to assess
      potential risks of endocrine-active chemicals.

PMID- 19767444
TI  - Establishment of an immunoglobulin m antibody-forming cell response model for
      characterizing immunotoxicity in primary human B cells.
AB  - Rodent models have been extensively utilized to identify putative human
      immunotoxicants; however, even when immunotoxicity is established, uncertainty
      remains whether the effects are predictive of human risk. Therefore, the
      objective of this study was to establish a polyclonal immunoglobulin M (IgM)
      antibody-forming cell (AFC) response model to directly characterize
      immunotoxicity in primary mouse or human B cells. CD40 ligand (CD40L) was
      selected to activate B cells because it effectively drives both primary human and
      mouse B cells in vitro to AFC in a physiologically relevant manner to mimic T
      cell-dependent antibody responses in vivo. In this model, the IgM AFC response is
      induced by cell surface-expressed CD40L and promoted by recombinant cytokines.
      Reported here are the conditions required to induce IgM AFC responses using mouse
      splenic B cells or human peripheral blood B cells, allowing for species
      comparisons. Moreover, less than one order of magnitude difference was observed
      in the CD40L-induced B-cell AFC responses based on data from multiple donors. In
      addition to antibody production, proliferation and phenotypic changes
      characteristic of B-cell activation as well as the plasma cell phenotype were
      also significantly induced. Finally, two well-characterized immunotoxicants,
      arsenic and benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide, using the CD40L-induced
      IgM AFC response were compared in both mouse and human B cells. Collectively, an
      IgM AFC response model is described that can be applied to assess the sensitivity
      of antibody responses to modulation by xenobiotics using mouse as well as human
      primary B cells.

PMID- 19767445
TI  - Immortalized human brain endothelial cell line HCMEC/D3 as a model of the blood
      brain barrier facilitates in vitro studies of central nervous system infection by
      Cryptococcus neoformans.
AB  - Cryptococcus neoformans cells must cross the blood-brain barrier prior to
      invading the central nervous system. Here we demonstrate that the immortalized
      human brain endothelial cell line HCMEC/D3 is a useful alternative to primary
      brain endothelial cells as a model of the blood-brain barrier for studies of
      central nervous system infection.

PMID- 19767446
TI  - Contrasting effects of allosteric and orthosteric agonists on m1 muscarinic
      acetylcholine receptor internalization and down-regulation.
AB  - A new class of subtype-selective muscarinic acetylcholine (mACh) receptor agonist
      that activates the receptor through interaction at a site distinct from the
      orthosteric acetylcholine binding site has been reported recently. Here, we have
      compared the effects of orthosteric (oxotremorine-M, arecoline, pilocarpine) and
      allosteric [4-n-butyl-1-[4-(2-methylphenyl)-4-oxo-1-butyl] piperidine (AC-42); 1
      [3-(4-butyl-1-piperidinyl)propyl]-3,4-dihydro-2(1H)-quinolinone (77-LH-28-1)]
      agonists on M(1) mACh receptor internalization and down-regulation, as well as
      functional coupling in a Chinese hamster ovary (CHO) cell line. In contrast to
      full and partial orthosteric agonists, which cause significant receptor
      internalization and down-regulation, prolonged exposure to AC-42 did not
      significantly alter either cell-surface or total cellular M(1) mACh receptor
      expression. 77-LH-28-1, an AC-42 homolog, did cause some receptor
      internalization, but not down-regulation. The presence of atropine completely
      prevented the orthosteric agonist-induced adaptive changes in receptor
      populations; however, in contrast, the copresence of atropine and AC-42
      significantly increased both cell-surface receptor and total M(1) mACh receptor
      expression. Maximal phosphoinositide hydrolysis responses to the partial agonist
      arecoline were similar in CHO-M(1) cells pretreated for 24 h with either AC-42 or
      vehicle; in contrast, these responses were markedly reduced when cells were
      pretreated with oxotremorine-M or pilocarpine. These data indicate that, whereas
      AC-42 binding to the M(1) mACh receptor can initiate signal transduction, the AC
      42-liganded receptor is resistant to the usual mechanisms regulating receptor
      internalization and down-regulation. In addition, our data suggest unusual
      interactions between allosteric agonists and orthosteric antagonists to regulate
      cell-surface and total cellular receptor expression.

PMID- 19767447
TI  - Administration of ampicillin elevates hepatic primary bile acid synthesis through
      suppression of ileal fibroblast growth factor 15 expression.
AB  - Administration of the antibacterial drug ampicillin (ABPC) significantly
      increased hepatic bile acid concentrations. In the present study, we investigated
      the mechanisms for the elevation of bile acid levels in ABPC-treated mice.
      Hepatic microsomal cholesterol 7alpha-hydroxylation and CYP7A1 mRNA level were
      increased 2.0-fold in ABPC-treated mice despite higher bile acid levels in the
      liver and small intestinal lumen. A significant change in hepatic small
      heterodimer partner (SHP) mRNA level was not observed in ABPC-treated mice,
      whereas a marked decrease in ileal fibroblast growth factor 15 (FGF15) mRNA level
      was observed (3% of vehicle-treated mice). These phenomena were also observed in
      mice cotreated with bacitracin/streptomycin/neomycin, which are barely absorbed
      from the intestine. Primary bile acid contents in the small intestinal lumen were
      increased in ABPC-treated mice, whereas secondary bile acid, deoxycholic acid
      (DCA), contents were reduced to below detection limits (<0.01 micromol). In ABPC
      treated mice, cotreatment with tauroDCA reversed reductions in ileal FGF15 mRNA
      level. Ileal SHP mRNA level was, however, not decreased in ABPC-treated mice.
      ABPC administration to farnesoid X receptor (Fxr)-null mice also decreased ileal
      FGF15 mRNA levels and secondary bile acid content in the small intestinal lumen.
      These results suggest that ABPC administration elevates hepatic primary bile acid
      synthesis, at least in part, through suppression of ileal FGF15 expression.

PMID- 19767448
TI  - Directed expression of Cre in alveolar epithelial type 1 cells.
AB  - Pulmonary alveolar epithelium is comprised of two morphologically and
      functionally distinct cell types, alveolar epithelial type (AT) I and AT2 cells.
      Genetically modified mice with cell-specific Cre/loxP-mediated knockouts of
      relevant genes in each respective cell type would be useful to help elucidate the
      relative contributions of AT1 versus AT2 cells to alveolar homeostasis. Cre has
      previously been efficiently expressed in AT2 cells in mouse lung with the
      surfactant protein (SP)-C promoter; however, no transgenic mouse expressing Cre
      in AT1 cells has so far been available. To develop an AT1 cell-specific
      transgenic Cre mouse, we generated a knockin of a Cre-IRES-DsRed cassette into
      exon 1 of the endogenous aquaporin 5 (Aqp5) gene, a gene expressed specifically
      in AT1 cells in the distal lung epithelium, resulting in the mouse line, Aqp5-Cre
      IRES-DsRed (ACID). Endogenous Aqp5 and transgenic Cre in ACID mice showed a very
      similar pattern of tissue distribution by RT-PCR. To analyze Cre activity, ACID
      was crossed to two Cre reporter strains, R26LacZ and mT/mG. Double-transgenic
      offspring demonstrated reporter gene expression in a very high fraction of AT1
      cells in the distal lung, whereas AT2 cells were negative. As expected, variable
      reporter expression was detected in several other tissues where endogenous Aqp5
      is expressed (e.g., submandibular salivary gland and stomach). ACID mice should
      be of major utility in analyzing the functional contribution of AT1 cells to
      alveolar epithelial properties in vivo with Cre/loxP-mediated gene deletion
      technology.

PMID- 19767449
TI  - Human airway contraction and formoterol-induced relaxation is determined by Ca2+
      oscillations and Ca2+ sensitivity.
AB  - The etiology of airway hyperresponsiveness associated with asthma requires an
      understanding of the regulatory mechanisms mediating human airway smooth muscle
      cell (SMC) contraction. The objective of this study was to determine how human
      airway SMC contraction (induced by histamine) and relaxation (induced by
      formoterol) are regulated by Ca(2+) oscillations and Ca(2+) sensitivity. The
      responses of human small airways and their associated SMCs were studied in human
      lung slices cut from agarose-inflated lungs. Airway contraction was measured with
      phase-contrast video microscopy. Ca(2+) signaling and Ca(2+) sensitivity of
      airway SMCs were measured with two-photon fluorescence microscopy and Ca(2+)
      permeabilized lung slices. The agonist histamine induced contraction of human
      small airways by stimulating both an increase in intracellular Ca(2+)
      concentration in the SMCs in the form of oscillatory Ca(2+) waves and an increase
      in Ca(2+) sensitivity. The frequency of the Ca(2+) oscillations increased with
      histamine concentration, and correlated with increased contraction. Formoterol
      induced airway relaxation at low concentrations by initially decreasing SMC
      Ca(2+) sensitivity. At higher concentrations, formoterol additionally slowed or
      inhibited the Ca(2+) oscillations of the SMCs to relax the airways. The action of
      formoterol was only slowly reversed. Human lung slices provide a powerful
      experimental assay for the investigation of small airway physiology and
      pharmacology. Histamine induces contraction by simultaneously increasing SMC
      Ca(2+) signaling and Ca(2+) sensitivity. Formoterol induces long-lasting
      relaxation by initially reducing the Ca(2+) sensitivity and, subsequently, the
      frequency of the Ca(2+) oscillations of the airway SMCs.

PMID- 19767450
TI  - Endothelial-mesenchymal transition in bleomycin-induced pulmonary fibrosis.
AB  - The pathological hallmark lesions in idiopathic pulmonary fibrosis are the
      fibroblastic foci, in which fibroblasts are thought to be involved in the tissue
      remodeling, matrix deposition, and cross-talk with alveolar epithelium. Recent
      evidence indicates that some fibroblasts in fibrosis may be derived from bone
      marrow progenitors as well as from epithelial cells through epithelial
      mesenchymal transition. To evaluate whether endothelial cells could represent an
      additional source for fibroblasts, bleomycin-induced lung fibrosis was
      established in Tie2-Cre/CAG-CAT-LacZ double-transgenic mice, in which LacZ was
      stably expressed in pan-endothelial cells. Combined X-gal staining and
      immunocytochemical staining for type I collagen and alpha-smooth muscle actin
      revealed the presence of X-gal-positive cells in lung fibroblast cultures from
      bleomycin-treated mice. To explore the underlying mechanisms, by which loss of
      endothelial-specific markers and gain of mesenchymal phenotypes could be involved
      in microvascular endothelial cells, the effects of activated Ras and TGF-beta on
      the microvascular endothelial cell line MS1 were analyzed. Combined treatment
      with activated Ras and TGF-beta caused a significant loss of endothelial-specific
      markers, while inducing de novo mesenchymal phenotypes. The altered expression of
      these markers in MS1 cells with activated Ras persisted after withdrawal of TGF
      beta in vitro and in vivo. These findings are the first to show that lung
      capillary endothelial cells could give rise to significant numbers of fibroblasts
      through an endothelial-mesenchymal transition in bleomycin-induced lung fibrosis
      model.

PMID- 19767451
TI  - Position 5.46 of the serotonin 5-HT2A receptor contributes to a species-dependent
      variation for the 5-HT2C agonist (R)-9-ethyl-1,3,4,10b-tetrahydro-7
      trifluoromethylpyrazino[2,1-a]isoindol-6(2H)-one: impact on selectivity and
      toxicological evaluation.
AB  - Successful development of 5-HT(2C) agonists requires selectivity versus the
      highly homologous 5-HT(2A) receptor, because agonism at this receptor can result
      in significant adverse events. (R)-9-Ethyl-1,3,4,10b-tetrahydro-7
      trifluoromethylpyrazino[2,1-a]isoindol-6(2H)-one (compound 1) is a potent 5
      HT(2C) agonist exhibiting selectivity over the human 5-HT(2A) receptor.
      Evaluation of the compound at the rat 5-HT(2A) receptor, however, revealed potent
      binding and agonist functional activity. The physiological consequence of this
      higher potency was the observation of a significant increase in blood pressure in
      conscious telemeterized rats that could be prevented by ketanserin. Docking of
      compound 1 in a homology model of the 5-HT(2A) receptor indicated a possible
      binding mode in which the ethyl group at the 9-position of the molecule was
      oriented toward position 5.46 of the 5-HT(2A) receptor. Within the human 5-HT(2A)
      receptor, position 5.46 is Ser242; however, in the rat 5-HT(2A) receptor, it is
      Ala242, suggesting that the potent functional activity in this species resulted
      from the absence of the steric bulk provided by the -OH moiety of the Ser in the
      human isoform. We confirmed this hypothesis using site-directed mutagenesis
      through the mutation of both the human receptor Ser242 to Ala and the rat
      receptor Ala242 to Ser, followed by radioligand binding and second messenger
      studies. In addition, we attempted to define the space allowed by the alanine by
      evaluating compounds with larger substitutions at the 9-position. The data
      indicate that position 5.46 contributed to the species difference in 5-HT(2A)
      receptor potency observed for a pyrazinoisoindolone compound, resulting in the
      observation of a significant cardiovascular safety signal.

PMID- 19767452
TI  - Monoacylglycerol lipase limits the duration of endocannabinoid-mediated
      depolarization-induced suppression of excitation in autaptic hippocampal neurons.
AB  - Depolarization-induced suppression of excitation (DSE) is a major form of
      cannabinoid-mediated short-term retrograde neuronal plasticity and is found in
      numerous brain regions. Autaptically cultured murine hippocampal neurons are an
      architecturally simple model for the study of cannabinoid signaling, including
      DSE. The transient nature of DSE--tens of seconds--is probably determined by the
      regulated hydrolysis of the endocannabinoid 2-arachidonoyl glycerol (2-AG). No
      less than five candidate enzymes have been considered to serve this role: fatty
      acid amide hydrolase (FAAH), cyclooxygenase-2 (COX-2), monoacylglycerol lipase
      (MGL), and alpha/beta-hydrolase domain (ABHD) 6 and 12. We previously found that
      FAAH and COX-2 do not have a role in determining the duration of autaptic DSE. In
      the current study, we found that two structurally distinct inhibitors of MGL [N
      arachidonoyl maleimide and 4-nitrophenyl 4-(dibenzo[d][1,3]dioxol-5
      yl(hydroxy)methyl)piperidine-1-carboxylate (JZL184)] prolong DSE in autaptic
      hippocampal neurons, whereas inhibition of ABHD6 by N-methyl-N-[[3-(4
      pyridinyl)phenyl]methyl]-4'-(aminocarbonyl)[1,1'-biphenyl]-4-yl ester, carbamic
      acid (WWL70) had no effect. In addition, we developed antibodies against MGL and
      ABHD6 and determined their expression in autaptic cultures. MGL is chiefly
      expressed at presynaptic terminals, optimally positioned to break down 2-AG that
      has engaged presynaptic CB(1) receptors. ABHD6 is expressed in two distinct
      locations on autaptic islands, including a prominent localization in some
      dendrites. In summary, we provide strong pharmacological and anatomical evidence
      that MGL regulates DSE in autaptic hippocampal neurons and, taken together with
      other studies, emphasizes that endocannabinoid signaling is terminated in
      temporally diverse ways.

PMID- 19767453
TI  - The rice alpha-amylase glycoprotein is targeted from the Golgi apparatus through
      the secretory pathway to the plastids.
AB  - The well-characterized secretory glycoprotein, rice (Oryza sativa) alpha-amylase
      isoform I-1 (AmyI-1), was localized within the plastids and proved to be involved
      in the degradation of starch granules in the organelles of rice cells. In
      addition, a large portion of transiently expressed AmyI-1 fused to green
      fluorescent protein (AmyI-1-GFP) colocalized with a simultaneously expressed
      fluorescent plastid marker in onion (Allium cepa) epidermal cells. The plastid
      targeting of AmyI-1 was inhibited by both dominant-negative and constitutively
      active mutants of Arabidopsis thaliana ARF1 and Arabidopsis SAR1, which arrest
      endoplasmic reticulum-to-Golgi traffic. In cells expressing fluorescent trans
      Golgi and plastid markers, these fluorescent markers frequently colocalized when
      coexpressed with AmyI-1. Three-dimensional time-lapse imaging and electron
      microscopy of high-pressure frozen/freeze-substituted cells demonstrated that
      contact of the Golgi-derived membrane vesicles with cargo and subsequent
      absorption into plastids occur within the cells. The transient expression of a
      series of C-terminal-truncated AmyI-1-GFP fusion proteins in the onion cell
      system showed that the region from Trp-301 to Gln-369 is necessary for plastid
      targeting of AmyI-1. Furthermore, the results obtained by site-directed mutations
      of Trp-302 and Gly-354, located on the surface and on opposite sides of the AmyI
      1 protein, suggest that multiple surface regions are necessary for plastid
      targeting. Thus, Golgi-to-plastid traffic appears to be involved in the transport
      of glycoproteins to plastids and plastid targeting seems to be accomplished in a
      sorting signal-dependent manner.

PMID- 19767454
TI  - The Arabidopsis RPW8 resistance protein is recruited to the extrahaustorial
      membrane of biotrophic powdery mildew fungi.

PMID- 19767455
TI  - Global identification of targets of the Arabidopsis MADS domain protein AGAMOUS
      Like15.
AB  - AGAMOUS-Like15 (AGL15) is a MADS domain transcriptional regulator that promotes
      somatic embryogenesis by binding DNA and regulating gene expression. Chromatin
      immunoprecipitation (ChIP) analysis previously identified DNA fragments with
      which AGL15 associates in vivo, and a low-throughput approach revealed a role for
      AGL15 in gibberellic acid catabolism that is relevant to embryogenesis. However,
      higher throughput methods are needed to identify targets of AGL15. Here, we
      mapped AGL15 in vivo binding sites using a ChIP-chip approach and the Affymetrix
      tiling arrays for Arabidopsis thaliana and found that approximately 2000 sites
      represented in three biological replicates of the experiment are annotated to
      nearby genes. These results were combined with high-throughput measurement of
      gene expression in response to AGL15 accumulation to discriminate responsive
      direct targets from those further downstream in the network. LEAFY COTYLEDON2,
      FUSCA3, and ABA INSENSITIVE3, which encode B3 domain transcription factors that
      are key regulators of embryogenesis, were identified and verified as direct
      target genes of AGL15. Genes identified as targets of the B3 genes are also
      targets of AGL15, and we found that INDOLEACETIC ACID-INDUCED PROTEIN30 is
      involved in promotion of somatic embryo development. The data presented here and
      elsewhere suggest that much cross-regulation occurs in gene regulatory networks
      underpinning embryogenesis.

PMID- 19767456
TI  - Genome-wide Medicago truncatula small RNA analysis revealed novel microRNAs and
      isoforms differentially regulated in roots and nodules.
AB  - Posttranscriptional regulation of a variety of mRNAs by small 21- to 24
      nucleotide RNAs, notably the microRNAs (miRNAs), is emerging as a novel
      developmental mechanism. In legumes like the model Medicago truncatula, roots are
      able to develop a de novo meristem through the symbiotic interaction with
      nitrogen-fixing rhizobia. We used deep sequencing of small RNAs from root apexes
      and nodules of M. truncatula to identify 100 novel candidate miRNAs encoded by
      265 hairpin precursors. New atypical precursor classes producing only specific 21
      and 24-nucleotide small RNAs were found. Statistical analysis on sequencing
      reads abundance revealed specific miRNA isoforms in a same family showing
      contrasting expression patterns between nodules and root apexes. The
      differentially expressed conserved and nonconserved miRNAs may target a large
      variety of mRNAs. In root nodules, which show diverse cell types ranging from a
      persistent meristem to a fully differentiated central region, we discovered
      miRNAs spatially enriched in nodule meristematic tissues, vascular bundles, and
      bacterial infection zones using in situ hybridization. Spatial regulation of
      miRNAs may determine specialization of regulatory RNA networks in plant
      differentiation processes, such as root nodule formation.

PMID- 19767457
TI  - A dual role for the S-locus receptor kinase in self-incompatibility and pistil
      development revealed by an Arabidopsis rdr6 mutation.
AB  - The coordinate evolution of self-incompatibility (SI) and stigma-anther
      separation, two mechanisms that promote cross-pollination in plants, has been a
      long-standing puzzle in evolution and development. Using a transgenic self
      incompatible Arabidopsis thaliana model, we performed screens for mutants
      exhibiting a modified SI response. A mutation in the RNA-dependent RNA polymerase
      RDR6, which functions in trans-acting short interfering RNA (ta-siRNA)
      production, was found that simultaneously enhances SI and causes stigma
      exsertion, without associated increases in SRK transcript levels. While rdr6
      mutants had been previously shown to exhibit stochastic stigma exsertion, our
      results demonstrate that the S-locus receptor kinase (SRK) gene further enhances
      pistil elongation and stigma exsertion in this mutant background, a process that
      requires SRK catalytic activity and correlates with SRK transcript levels. These
      results suggest that positive regulators or effectors of SI and pistil
      development are regulated by ta-siRNA(s). By establishing complex connections
      between SI and stigma exsertion through the sharing of a ta-siRNA-mediated
      regulatory pathway and the dual role of SRK in SI and pistil development, our
      study provides a molecular explanation for the coordinate evolution of these
      processes.

PMID- 19767458
TI  - Establishing molecular tools for genetic manipulation of the pleuromutilin
      producing fungus Clitopilus passeckerianus.
AB  - We describe efficient polyethylene glycol (PEG)-mediated and Agrobacterium
      mediated transformation systems for a pharmaceutically important basidiomycete
      fungus, Clitopilus passeckerianus, which produces pleuromutilin, a diterpene
      antibiotic. Three dominant selectable marker systems based on hygromycin,
      phleomycin, and carboxin selection were used to study the feasibility of PEG
      mediated transformation of C. passeckerianus. The PEG-mediated transformation of
      C. passeckerianus protoplasts was successful and generated hygromycin-resistant
      transformants more efficiently than either phleomycin or carboxin resistance.
      Agrobacterium-mediated transformation with plasmid pBGgHg containing hph gene
      under the control of the Agaricus bisporus gpdII promoter led to hygromycin
      resistant colonies and was successful when homogenized mycelium and fruiting body
      gill tissue were used as starting material. Southern blot analysis of
      transformants revealed the apparently random integration of the transforming DNA
      to be predominantly multiple copies for the PEG-mediated system and a single copy
      for the Agrobacterium-mediated system within the genome. C. passeckerianus actin
      and tubulin promoters were amplified from genomic DNA and proved successful in
      driving green fluorescent protein and DsRed expression in C. passeckerianus, but
      only when constructs contained a 5' intron, demonstrating that the presence of an
      intron is prerequisite for efficient transgene expression. The feasibility of RNA
      interference-mediated gene silencing was investigated using gfp as a target gene
      easily scored in C. passeckerianus. Upon transformation of gfp antisense
      constructs into a highly fluorescent strain, transformants were recovered that
      exhibited either reduced or undetectable fluorescence. This was confirmed by
      Northern blotting showing depletion of the target mRNA levels. This demonstrated
      that gene silencing is a suitable tool for modulating gene expression in C.
      passeckerianus. The molecular tools developed in this study should facilitate
      studies aimed at gene isolation or characterization in this pharmaceutically
      important species.

PMID- 19767459
TI  - Molecular identification and hidden diversity of novel Daphnia parasites from
      European lakes.
AB  - Parasites play important roles in local population dynamics and genetic
      structure. However, due to insufficient diagnostic tools, detailed host-parasite
      interactions may remain concealed by hidden parasite diversity in natural
      systems. Microscopic examination of 19 European lake Daphnia populations revealed
      the presence of three groups of parasites: fungi, microsporidia, and oomycetes.
      For most of these parasites no genetic markers have been described so far. Based
      on sequence similarities of the nuclear small-subunit and internal transcribed
      spacer (ITS) rRNA gene regions, one fungus, four microsporidian, and nine
      oomycete taxa were discovered in 147 infected Daphnia (and/or three other
      zooplankton crustaceans). Additionally, cloning of rRNA gene regions revealed
      parasite sequence variation within host individuals. This was most pronounced in
      the ITS region of one microsporidian taxon, where the within-host sequence
      variation ranged from 1.7% to 5.3% polymorphic sites for parasite isolates from
      14 different geographical locations. Interestingly, the parasite isolates from
      close locations grouped together based on sequence similarities, suggesting that
      there was parasite dispersal. Taken together, the data obtained in this study
      revealed hidden diversity of parasite communities in Daphnia lake populations.
      Moreover, a higher level of resolution for identifying parasite strains makes it
      possible to test new hypotheses with respect to parasite dispersal, transmission
      routes, and coinfection.

PMID- 19767460
TI  - Thermostable cyanuric acid hydrolase from Moorella thermoacetica ATCC 39073.
AB  - Cyanuric acid, a metabolic intermediate in the degradation of many s-triazine
      compounds, is further metabolized by cyanuric acid hydrolase. Cyanuric acid also
      accumulates in swimming pools due to the breakdown of the sanitizing agents di-
      and trichloroisocyanuric acid. Structurally stable cyanuric acid hydrolases are
      being considered for usage in pool water remediation. In this study, cyanuric
      acid hydrolase from the thermophile Moorella thermoacetica ATCC 39073 was cloned,
      expressed in Escherichia coli, and purified to homogeneity. The recombinant
      enzyme was found to have a broader temperature range and greater stability, at
      both elevated and low temperatures, than previously described cyanuric acid
      hydrolases. The enzyme had a narrow substrate specificity, acting only on
      cyanuric acid and N-methylisocyanuric acid. The M. thermoacetica enzyme did not
      require metals or other discernible cofactors for activity. Cyanuric acid
      hydrolase from M. thermoacetica is the most promising enzyme to use for cyanuric
      acid remediation applications.

PMID- 19767461
TI  - Development of a log-quadratic model to describe microbial inactivation,
      illustrated by thermal inactivation of Clostridium botulinum.
AB  - In the commercial food industry, demonstration of microbiological safety and
      thermal process equivalence often involves a mathematical framework that assumes
      log-linear inactivation kinetics and invokes concepts of decimal reduction time
      (D(T)), z values, and accumulated lethality. However, many microbes, particularly
      spores, exhibit inactivation kinetics that are not log linear. This has led to
      alternative modeling approaches, such as the biphasic and Weibull models, that
      relax strong log-linear assumptions. Using a statistical framework, we developed
      a novel log-quadratic model, which approximates the biphasic and Weibull models
      and provides additional physiological interpretability. As a statistical linear
      model, the log-quadratic model is relatively simple to fit and straightforwardly
      provides confidence intervals for its fitted values. It allows a D(T)-like value
      to be derived, even from data that exhibit obvious "tailing." We also showed how
      existing models of non-log-linear microbial inactivation, such as the Weibull
      model, can fit into a statistical linear model framework that dramatically
      simplifies their solution. We applied the log-quadratic model to thermal
      inactivation data for the spore-forming bacterium Clostridium botulinum and
      evaluated its merits compared with those of popular previously described
      approaches. The log-quadratic model was used as the basis of a secondary model
      that can capture the dependence of microbial inactivation kinetics on
      temperature. This model, in turn, was linked to models of spore inactivation of
      Sapru et al. and Rodriguez et al. that posit different physiological states for
      spores within a population. We believe that the log-quadratic model provides a
      useful framework in which to test vitalistic and mechanistic hypotheses of
      inactivation by thermal and other processes.

PMID- 19767462
TI  - Quadruplex real-time PCR assay for detection and identification of Vibrio
      cholerae O1 and O139 strains and determination of their toxigenic potential.
AB  - Vibrio cholerae is a natural inhabitant of the aquatic environment. However, its
      toxigenic strains can cause potentially life-threatening diarrhea. A quadruplex
      real-time PCR assay targeting four genes, the cholera toxin gene (ctxA), the
      hemolysin gene (hlyA), O1-specific rfb, and O139-specific rfb, was developed for
      detection and differentiation of O1, O139, and non-O1, non-O139 strains and for
      prediction of their toxigenic potential. The specificity of the assay was 100%
      when tested against 70 strains of V. cholerae and 31 strains of non-V. cholerae
      organisms. The analytical sensitivity for detection of toxigenic V. cholerae O1
      and O139 was 2 CFU per reaction with cells from pure culture. When the assay was
      tested with inoculated water from bullfrog feeding ponds, 10 CFU/ml could
      reliably be detected after culture for 3 h. The assay was more sensitive than the
      immunochromatographic assay and culture method when tested against 89 bullfrog
      samples and 68 water samples from bullfrog feeding ponds. The applicability of
      this assay was confirmed in a case study involving 15 bullfrog samples, from
      which two mixtures of nontoxigenic O1 and toxigenic non-O1/non-O139 strains were
      detected and differentiated. These data indicate that the quadruplex real-time
      PCR assay can both rapidly and accurately detect/identify V. cholerae and
      reliably predict the toxigenic potential of strains detected.

PMID- 19767463
TI  - The olive fly endosymbiont, "Candidatus Erwinia dacicola," switches from an
      intracellular existence to an extracellular existence during host insect
      development.
AB  - As polyphagous, holometabolous insects, tephritid fruit flies (Diptera:
      Tephritidae) provide a unique habitat for endosymbiotic bacteria, especially
      those microbes associated with the digestive system. Here we examine the
      endosymbiont of the olive fly [Bactrocera oleae (Rossi) (Diptera: Tephritidae)],
      a tephritid of great economic importance. "Candidatus Erwinia dacicola" was found
      in the digestive systems of all life stages of wild olive flies from the
      southwestern United States. PCR and microscopy demonstrated that "Ca. Erwinia
      dacicola" resided intracellularly in the gastric ceca of the larval midgut but
      extracellularly in the lumen of the foregut and ovipositor diverticulum of adult
      flies. "Ca. Erwinia dacicola" is one of the few nonpathogenic endosymbionts that
      transitions between intracellular and extracellular lifestyles during specific
      stages of the host's life cycle. Another unique feature of the olive fly
      endosymbiont is that unlike obligate endosymbionts of monophagous insects, "Ca.
      Erwinia dacicola" has a G+C nucleotide composition similar to those of closely
      related plant-pathogenic and free-living bacteria. These two characteristics of
      "Ca. Erwinia dacicola," the ability to transition between intracellular and
      extracellular lifestyles and a G+C nucleotide composition similar to those of
      free-living relatives, may facilitate survival in a changing environment during
      the development of a polyphagous, holometabolous host. We propose that insect
      bacterial symbioses should be classified based on the environment that the host
      provides to the endosymbiont (the endosymbiont environment).

PMID- 19767464
TI  - Bacteria, archaea, and crenarchaeota in the epilimnion and hypolimnion of a deep
      holo-oligomictic lake.
AB  - In a deep, subalpine holo-oligomictic lake, the relative abundance of Archaea and
      Crenarchaeota, but not that of Bacteria, increases significantly with depth and
      varies seasonally. Cell-specific prokaryotic productivity is homogeneous along
      the water column. The concept of active Archaea observed in the deep ocean can
      therefore be extended to a deep oxic lake.

PMID- 19767465
TI  - Improved squalene production via modulation of the methylerythritol 4-phosphate
      pathway and heterologous expression of genes from Streptomyces peucetius ATCC
      27952 in Escherichia coli.
AB  - Putative hopanoid genes from Streptomyces peucetius were introduced into
      Escherichia coli to improve the production of squalene, an industrially important
      compound. High expression of hopA and hopB (encoding squalene/phytoene synthases)
      together with hopD (encoding farnesyl diphosphate synthase) yielded 4.1 mg/liter
      of squalene. This level was elevated to 11.8 mg/liter when there was also
      increased expression of dxs and idi, E. coli genes encoding 1-deoxy-d-xylulose 5
      phosphate synthase and isopentenyl diphosphate isomerase.

PMID- 19767466
TI  - Novel GH10 xylanase, with a fibronectin type 3 domain, from Cellulosimicrobium
      sp. strain HY-13, a bacterium in the gut of Eisenia fetida.
AB  - The gene encoding a novel modular xylanase from Cellulosimicrobium sp. strain HY
      13 was identified and expressed in Escherichia coli, and its truncated gene
      product was characterized. The enzyme consisted of three distinct functional
      domains, an N-terminal catalytic GH10 domain, a fibronectin type 3 domain, and C
      terminal carbohydrate-binding module 2.

PMID- 19767467
TI  - ATP-dependent but proton gradient-independent polyphosphate-synthesizing activity
      in extraradical hyphae of an arbuscular mycorrhizal fungus.
AB  - Arbuscular mycorrhizal (AM) fungi benefit their host plants by supplying
      phosphate obtained from the soil. Polyphosphate is thought to act as the key
      intermediate in this process, but little is currently understood about how
      polyphosphate is synthesized or translocated within arbuscular mycorrhizas.
      Glomus sp. strain HR1 was grown with marigold in a mesh bag compartment system,
      and extraradical hyphae were harvested and fractionated by density gradient
      centrifugation. Using this approach, three distinct layers were obtained: layers
      1 and 2 were composed of amorphous and membranous materials, together with
      mitochondria, lipid bodies, and electron-opaque bodies, and layer 3 was composed
      mainly of partially broken hyphae and fragmented cell walls. The polyphosphate
      kinase/luciferase system, a highly sensitive polyphosphate detection method,
      enabled the detection of polyphosphate-synthesizing activity in layer 2 in the
      presence of ATP. This activity was inhibited by vanadate but not by bafilomycin
      A(1) or a protonophore, suggesting that ATP may not energize the reaction through
      H(+)-ATPase but may act as a direct substrate in the reaction. This report
      represents the first demonstration that AM fungi possess polyphosphate
      synthesizing activity that is localized in the organelle fraction and not in the
      cytosol or at the plasma membrane.

PMID- 19767469
TI  - Identification and classification of bcl genes and proteins of Bacillus cereus
      group organisms and their application in Bacillus anthracis detection and
      fingerprinting.
AB  - The Bacillus cereus group includes three closely related species, B. anthracis,
      B. cereus, and B. thuringiensis, which form a highly homogeneous subdivision of
      the genus Bacillus. One of these species, B. anthracis, has been identified as
      one of the most probable bacterial biowarfare agents. Here, we evaluate the
      sequence and length polymorphisms of the Bacillus collagen-like protein bcl genes
      as a basis for B. anthracis detection and fingerprinting. Five genes, designated
      bclA to bclE, are present in B. anthracis strains. Examination of bclABCDE
      sequences identified polymorphisms in bclB alleles of the B. cereus group
      organisms. These sequence polymorphisms allowed specific detection of B.
      anthracis strains by PCR using both genomic DNA and purified Bacillus spores in
      reactions. By exploiting the length variation of the bcl alleles it was
      demonstrated that the combined bclABCDE PCR products generate markedly different
      fingerprints for the B. anthracis Ames and Sterne strains. Moreover, we predict
      that bclABCDE length polymorphism creates unique signatures for B. anthracis
      strains, which facilitates identification of strains with specificity and
      confidence. Thus, we present a new diagnostic concept for B. anthracis detection
      and fingerprinting, which can be used alone or in combination with previously
      established typing platforms.

PMID- 19767470
TI  - Identification of Bacillus anthracis by using matrix-assisted laser desorption
      ionization-time of flight mass spectrometry and artificial neural networks.
AB  - This report demonstrates the applicability of a combination of matrix-assisted
      laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS) and
      chemometrics for rapid and reliable identification of vegetative cells of the
      causative agent of anthrax, Bacillus anthracis. Bacillus cultures were prepared
      under standardized conditions and inactivated according to a recently developed
      MS-compatible inactivation protocol for highly pathogenic microorganisms. MALDI
      TOF MS was then employed to collect spectra from the microbial samples and to
      build up a database of bacterial reference spectra. This database comprised mass
      peak profiles of 374 strains from Bacillus and related genera, among them 102
      strains of B. anthracis and 121 strains of B. cereus. The information contained
      in the database was investigated by means of visual inspection of gel view
      representations, univariate t tests for biomarker identification, unsupervised
      hierarchical clustering, and artificial neural networks (ANNs). Analysis of gel
      views and independent t tests suggested B. anthracis- and B. cereus group
      specific signals. For example, mass spectra of B. anthracis exhibited
      discriminating biomarkers at 4,606, 5,413, and 6,679 Da. A systematic search in
      proteomic databases allowed tentative assignment of some of the biomarkers to
      ribosomal protein or small acid-soluble proteins. Multivariate pattern analysis
      by unsupervised hierarchical cluster analysis further revealed a subproteome
      based taxonomy of the genus Bacillus. Superior classification accuracy was
      achieved when supervised ANNs were employed. For the identification of B.
      anthracis, independent validation of optimized ANN models yielded a diagnostic
      sensitivity of 100% and a specificity of 100%.

PMID- 19767471
TI  - Hydroxylation and further oxidation of delta9-tetrahydrocannabinol by alkane
      degrading bacteria.
AB  - The microbial biotransformation of Delta(9)-tetrahydrocannabinol was investigated
      using a collection of 206 alkane-degrading strains. Fifteen percent of these
      strains, mainly gram-positive strains from the genera Rhodococcus, Mycobacterium,
      Gordonia, and Dietzia, yielded more-polar derivatives. Eight derivatives were
      produced on a mg scale, isolated, and purified, and their chemical structures
      were elucidated with the use of liquid chromatography-mass spectrometry, (1)H
      nuclear magnetic resonance (1H-NMR), and two-dimensional NMR (1H-1H correlation
      spectroscopy and heteronuclear multiple bond coherence). All eight
      biotransformation products possessed modified alkyl chains, with hydroxy,
      carboxy, and ester functionalities. In a number of strains, beta-oxidation of the
      initially formed C5 carboxylic acid led to the formation of a carboxylic acid
      lacking two methylene groups.

PMID- 19767468
TI  - Microbial populations responsive to denitrification-inducing conditions in rice
      paddy soil, as revealed by comparative 16S rRNA gene analysis.
AB  - Rice paddy soil has been shown to have strong denitrifying activity. However, the
      microbial populations responsible for nitrate respiration and denitrification
      have not been well characterized. In this study, we performed a clone library
      analysis of >1,000 clones of the nearly full-length 16S rRNA gene to characterize
      bacterial community structure in rice paddy soil. We also identified potential
      key players in nitrate respiration and denitrification by comparing the community
      structures of soils with strong denitrifying activity to those of soils without
      denitrifying activity. Clone library analysis showed that bacteria belonging to
      the phylum Firmicutes, including a unique Symbiobacterium clade, dominated the
      clones obtained in this study. Using the template match method, several
      operational taxonomic units (OTUs), most belonging to the orders Burkholderiales
      and Rhodocyclales, were identified as OTUs that were specifically enriched in the
      sample with strong denitrifying activity. Almost one-half of these OTUs were
      classified in the genus Herbaspirillum and appeared >10-fold more frequently in
      the soils with strong denitrifying activity than in the soils without
      denitrifying activity. Therefore, OTUs related to Herbaspirillum are potential
      key players in nitrate respiration and denitrification under the conditions used.

PMID- 19767472
TI  - Low taxon richness of bacterioplankton in high-altitude lakes of the eastern
      tibetan plateau, with a predominance of Bacteroidetes and Synechococcus spp.
AB  - Plankton samples were collected from six remote freshwater and saline lakes
      located at altitudes of 3,204 to 4,718 m and 1,000 km apart within an area of ca.
      1 million km(2) on the eastern Tibetan Plateau to comparatively assess how
      environmental factors influence the diversity of bacterial communities in high
      altitude lakes. The composition of the bacterioplankton was investigated by
      analysis of large clone libraries of 16S rRNA genes. Comparison of
      bacterioplankton diversities estimated for the six Tibetan lakes with reference
      data previously published for lakes located at lower altitudes indicated
      relatively low taxon richness in the Tibetan lakes. The estimated average taxon
      richness in the four Tibetan freshwater lakes was only one-fifth of the average
      taxon richness estimated for seven low-altitude reference lakes. This cannot be
      explained by low coverage of communities in the Tibetan lakes by the established
      libraries or by differences in habitat size. Furthermore, a comparison of the
      taxonomic compositions of bacterioplankton across the six Tibetan lakes revealed
      low overlap between their community compositions. About 70.9% of the operational
      taxonomic units (99% similarity) were specific to single lakes, and a relatively
      high percentage (11%) of sequences were <95% similar to publicly deposited
      sequences of cultured or uncultured bacteria. This beta diversity was explained
      by differences in salinity between lakes rather than by distance effects. Another
      characteristic of the investigated lakes was the predominance of Cyanobacteria
      (Synechococcus) and Bacteroidetes. These features of bacterioplankton diversity
      may reflect specific adaptation of various lineages to the environmental
      conditions in these high-altitude lakes.

PMID- 19767473
TI  - Bacterial community composition of stream biofilms in spatially variable-flow
      environments.
AB  - Streams are highly heterogeneous ecosystems, in terms of both geomorphology and
      hydrodynamics. While flow is recognized to shape the physical architecture of
      benthic biofilms, we do not yet understand what drives community assembly and
      biodiversity of benthic biofilms in the heterogeneous flow landscapes of streams.
      Within a metacommunity ecology framework, we experimented with streambed
      landscapes constructed from bedforms in large-scale flumes to illuminate the role
      of spatial flow heterogeneity in biofilm community composition and biodiversity
      in streams. Our results show that the spatial variation of hydrodynamics
      explained a remarkable percentage (up to 47%) of the variation in community
      composition along bedforms. This suggests species sorting as a model of
      metacommunity dynamics in stream biofilms, though natural biofilm communities
      will clearly not conform to a single model offered by metacommunity ecology. The
      spatial variation induced by the hydrodynamics along the bedforms resulted in a
      gradient of bacterial beta diversity, measured by a range of diversity and
      similarity indices, that increased with bedform height and hence with spatial
      flow heterogeneity at the flume level. Our results underscore the necessity to
      maintain small-scale physical heterogeneity for community composition and
      biodiversity of biofilms in stream ecosystems.

PMID- 19767474
TI  - Pepper mild mottle virus as an indicator of fecal pollution.
AB  - Accurate indicators of fecal pollution are needed in order to minimize public
      health risks associated with wastewater contamination in recreational waters.
      However, the bacterial indicators currently used for monitoring water quality do
      not correlate with the presence of pathogens. Here we demonstrate that the plant
      pathogen Pepper mild mottle virus (PMMoV) is widespread and abundant in
      wastewater from the United States, suggesting the utility of this virus as an
      indicator of human fecal pollution. Quantitative PCR was used to determine the
      abundance of PMMoV in raw sewage, treated wastewater, seawater exposed to
      wastewater, and fecal samples and/or intestinal homogenates from a wide variety
      of animals. PMMoV was present in all wastewater samples at concentrations greater
      than 1 million copies per milliliter of raw sewage. Despite the ubiquity of PMMoV
      in human feces, this virus was not detected in the majority of animal fecal
      samples tested, with the exception of chicken and seagull samples. PMMoV was
      detected in four out of six seawater samples collected near point sources of
      secondary treated wastewater off southeastern Florida, where it co-occurred with
      several other pathogens and indicators of fecal pollution. Since PMMoV was not
      found in nonpolluted seawater samples and could be detected in surface seawater
      for approximately 1 week after its initial introduction, the presence of PMMoV in
      the marine environment reflects a recent contamination event. Together, these
      data demonstrate that PMMoV is a promising new indicator of fecal pollution in
      coastal environments.

PMID- 19767475
TI  - Molecular characterization of bacteriophages for microbial source tracking in
      Korea.
AB  - We investigated coliphages from various fecal sources, including humans and
      animals, for microbial source tracking in South Korea. Both somatic and F+
      specific coliphages were isolated from 43 fecal samples from farms, wild animal
      habitats, and human wastewater plants. Somatic coliphages were more prevalent and
      abundant than F+ coliphages in all of the tested fecal samples. We further
      characterized 311 F+ coliphage isolates using RNase sensitivity assays, PCR and
      reverse transcription-PCR, and nucleic acid sequencing. Phylogenetic analyses
      were performed based on the partial nucleic acid sequences of 311 F+ coliphages
      from various sources. F+ RNA coliphages were most prevalent among geese (95%) and
      were least prevalent in cows (5%). Among the genogroups of F+ RNA coliphages,
      most F+ coliphages isolated from animal fecal sources belonged to either group I
      or group IV, and most from human wastewater sources were in group II or III. Some
      of the group I coliphages were present in both human and animal source samples.
      F+ RNA coliphages isolated from various sources were divided into two main
      clusters. All F+ RNA coliphages isolated from human wastewater were grouped with
      Qbeta-like phages, while phages isolated from most animal sources were grouped
      with MS2-like phages. UniFrac significance statistical analyses revealed
      significant differences between human and animal bacteriophages. In the principal
      coordinate analysis (PCoA), F+ RNA coliphages isolated from human waste were
      distinctively separate from those isolated from other animal sources. However, F+
      DNA coliphages were not significantly different or separate in the PCoA. These
      results demonstrate that proper analysis of F+ RNA coliphages can effectively
      distinguish fecal sources.

PMID- 19767476
TI  - Listeria monocytogenes attachment to and detachment from stainless steel surfaces
      in a simulated dairy processing environment.
AB  - The presence of pathogens in dairy products is often associated with
      contamination via bacteria attached to food-processing equipment, especially from
      areas where cleaning/sanitation is difficult. In this study, the attachment of
      Listeria monocytogenes on stainless steel (SS), followed by detachment and growth
      in foods, was evaluated under conditions simulating a dairy processing
      environment. Initially, SS coupons were immersed in milk, vanilla custard, and
      yogurt inoculated with the pathogen (10(7) CFU/ml or CFU/g) and incubated at two
      temperatures (5 and 20 degrees C) for 7 days. By the end of incubation, cells
      were mechanically detached from coupons and used to inoculate freshly pasteurized
      milk which was subsequently stored at 5 degrees C for 20 days. The suspended
      cells in all three products in which SS coupons were immersed were also used to
      inoculate freshly pasteurized milk (5 degrees C for 20 days). When SS coupons
      were immersed in milk, shorter lag phases were obtained for detached than for
      planktonically grown cells, regardless of the preincubation temperature (5 or 20
      degrees C). The opposite was observed when custard incubated at 20 degrees C was
      used to prepare the two types of inocula. However, in this case, a significant
      increase in growth rate was also evident when the inoculum was derived from
      detached cells. In another parallel study, while L. monocytogenes was not
      detectable on SS coupons after 7 days of incubation (at 5 degrees C) in
      inoculated yogurt, marked detachment and growth were observed when these coupons
      were subsequently transferred and incubated at 5 degrees C in fresh milk or/and
      custard. Overall, the results obtained extend our knowledge on the risk related
      to contamination of dairy products with detached L. monocytogenes cells.

PMID- 19767477
TI  - Quantification of the relative effects of temperature, pH, and water activity on
      inactivation of Escherichia coli in fermented meat by meta-analysis.
AB  - Outbreaks of Escherichia coli infections linked to fermented meats have prompted
      much research into the kinetics of E. coli inactivation during fermented meat
      manufacture. A meta-analysis of data from 44 independent studies was undertaken
      that allowed the relative influences of pH, water activity (a(w)), and
      temperature on E. coli survival during fermented meat processing to be
      investigated. Data were reevaluated to determine rates of inactivation, providing
      484 rate data points with various pH (2.8 to 6.14), a(w) (0.75 to 0.986), and
      temperature (-20 to 66 degrees C) values, product formulations, and E. coli
      strains and serotypes. When the data were presented as an Arrhenius model,
      temperature (0 to 47 degrees C) accounted for 61% of the variance in the
      ln(inactivation rate) data. In contrast, the pH or a(w) measured accounted for
      less than 8% of variability in the data, and the effects of other pH- and a(w)
      based variables (i.e., total decrease and rates of reduction of those factors)
      were largely dependent on the temperature of the process. These findings indicate
      that although temperatures typically used in fermented meat manufacture are not
      lethal to E. coli per se, when other factors prevent E. coli growth (e.g., low pH
      and a(w)), the rate of inactivation of E. coli is dominated by temperature. In
      contrast, inactivation rates at temperatures above approximately 50 degrees C
      were characterized by smaller z values than those at 0 to 47 degrees C,
      suggesting that the mechanisms of inactivation are different in these temperature
      ranges. The Arrhenius model developed can be used to improve product safety by
      quantifying the effects of changes in temperature and/or time on E. coli
      inactivation during fermented meat manufacture.

PMID- 19767478
TI  - Complex phenotypic and genotypic responses of Listeria monocytogenes strains
      exposed to the class IIa bacteriocin sakacin P.
AB  - Sakacin P is a class IIa bacteriocin that is active against the food-borne
      pathogen Listeria monocytogenes, and use of this compound as a biopreservative in
      foods has been suggested. In the present study, we characterized 30 spontaneous
      sakacin P-resistant mutants of L. monocytogenes obtained after single exposure to
      sakacin P. The frequency of development of sakacin P resistance for all strains
      was in the range from 10(-8) to 10(-9). Using the 50% inhibitory concentration
      (IC(50)) of sakacin P, the strains could be grouped into strains with high levels
      of resistance (IC(50), > or =10(4) ng ml(-1)) and strains with low levels of
      resistance (IC(50), <10(4) ng ml(-1)). Resistant strains belonging to the same
      IC(50) group also had similar physiological and genetic characteristics.
      Generally, the resistant strains showed substantial variations in many
      parameters, such as differences in the stability of the acquired resistance to
      sakacin P, growth fitness, food-related stress tolerance, and biofilm-forming
      ability. Fourier transform infrared spectroscopy revealed differences between
      wild-type and resistant strains in polysaccharide, fatty acid, and, protein
      regions. A mannose-specific phosphotransferase (PTS) operon has been described
      for class IIa bacteriocin resistance, and the sakacin P-resistant strains
      displayed both up- and downregulation of the expression of the mptA gene encoding
      the PTS system. This is the first comprehensive study of the diversity of a large
      number of spontaneous resistant mutants obtained after one exposure to a class
      IIa bacteriocin, particularly to sakacin P. The great diversity among the
      resistant strains exposed to the same stress conditions suggests that there are
      different resistance mechanisms.

PMID- 19767479
TI  - Comparison of point-of-use technologies for emergency disinfection of sewage
      contaminated drinking water.
AB  - Four point-of-use disinfection technologies for treating sewage-contaminated well
      water were compared. Three systems, based on flocculant-disinfectant packets and
      N-halamine chlorine and bromine contact disinfectants, provided a range of 4.0 to
      >6.6 log(10) reductions (LR) of naturally occurring fecal indicator and
      heterotrophic bacteria and a range of 0.9 to >1.9 LR of coliphage.

PMID- 19767480
TI  - Osteopathic medicine and the silver tsunami: preparing tomorrow's first
      responders for the elder boom.
AB  - In response to the shifting demographics observed in the United States, a variety
      of organizations have begun issuing consensus statements and patient care
      guidelines to help health professionals meet the anticipated medical needs of the
      older population. The authors describe a collaborative effort within the
      osteopathic medical profession focused on translating geriatric core competencies
      into curricula guidelines for osteopathic medical education. Osteopathic
      physicians will likely be the "first responders" for elder care needs in the
      United States as a result of their disproportionately high rates of primary care
      practice.

PMID- 19767481
TI  - Curricular analysis of competency-based osteopathic medical education:
      application of a matrix for quality enhancement to a standardized patient
      encounter example.
AB  - CONTEXT: With the formal adoption of the seven core competencies, the American
      Osteopathic Association's Commission on Osteopathic College Accreditation
      instructed osteopathic medical educators to guide curricular development with
      these goals in mind. Tools to facilitate and monitor these purposes have been
      under development separately at each of the nation's colleges of osteopathic
      medicine. OBJECTIVE: To demonstrate the utility of a checklist-based curriculum
      assessment tool, the Matrix for Quality Enhancement, as developed at Kirksville
      (Mo) College of Osteopathic Medicine-A.T. Still University. METHODS: APPLICATION
      of the Matrix is illustrated using examples selected from our analysis of a set
      of 16 standardized patient encounters provided as part of a first-year basic
      science course in medical microbiology. Encounters were developed to improve
      student understanding of infectious disease entities while also providing a
      variety of clinical experiences. Feedback on professionalism and humanistic
      behaviors was also provided. A novel aspect of the Matrix is the inclusion of a
      component dealing with patient safety. APPLICATION: Adding standardized patient
      encounters to the medical microbiology teaching program at Kirksville College of
      Osteopathic Medicine was an effective means of integrating educational
      experiences with the seven core competencies, the requirements of Comprehensive
      Osteopathic Medical Licensing Examination-USA Level 2-PE (Performance
      Evaluation), and patient safety issues. CONCLUSION: The Matrix is a valuable tool
      for evaluating or developing curricular components that maintain osteopathic
      integrity while working toward standards for medical education specified by the
      commission.

PMID- 19767482
TI  - Impact of Medicare Part D on osteopathic physicians.
AB  - CONTEXT: Although there is a wealth of information for patients and physicians on
      the Medicare Prescription Drug, Improvement, and Modernization Act, little
      research exists related to its impact on osteopathic physicians (DOs). OBJECTIVE:
      To examine the impact of Medicare's prescription drug benefit-or Part D-on DOs
      and their practices. METHODS: Two electronic surveys regarding Medicare Part D
      were e-mailed to DOs randomly selected from the American Osteopathic Association
      database. The first survey was sent January 31, 2006 (within the first month of
      Part D implementation), and the second was sent June 1, 2006 (6 months after
      implementation). Both surveys focused primarily on the challenges experienced by
      DOs and their staff regarding Part D. Responses were subjected to univariate,
      bivariate, and Pearson product moment correlation analysis. RESULTS: Of the
      10,000 DOs contacted, 603 (6%) responded and met inclusion criteria for the first
      survey and 343 (3.4%) for the second survey. More than 60% of respondents to the
      first survey reported challenges such as increased workload, difficulties
      understanding Part D, difficulties with the physician appeals process, and lack
      of information and education. These challenges were also reported in the second
      survey but by approximately 30% fewer respondents. One challenge-changing
      medications as a result of formulary restrictions-was reported by 17% more
      respondents to the second survey (P<.01). Respondents in primary care, solo
      practice, and rural areas as well as those treating large Medicare populations
      and those who were their patients' primary source of information about Part D
      reported more challenges. CONCLUSION: Considering the numerous challenges
      respondents faced with Part D, it is important to remember the role of physicians
      in successfully implementing healthcare programs, particularly as the US
      healthcare reform debate progresses.

PMID- 19767483
TI  - Management of chronic posttraumatic headache: a multidisciplinary approach.
AB  - Although the definitions and possible treatments of posttraumatic headache have
      been discussed in the literature, treatment of this condition is not
      standardized. In addition, though various reviews and case studies have supported
      the use of spinal manipulation in the treatment of tension-type headaches and
      migraines, few describe the use of osteopathic manipulative treatment for
      patients with posttraumatic headache. In describing a 38-year-old woman with
      posttraumatic headache, we illustrate a multidisciplinary approach-including the
      use of osteopathic principles and practice-to treating patients with
      posttraumatic headache.

PMID- 19767484
TI  - The Australasian College of Phlebology and its role.

PMID- 19767485
TI  - Arterio-venous malformation: how much do we know?
AB  - Arterio-venous malformation (AVM) is a congenital vascular malformation that is
      neither a venous malformation nor a haemangioma. An AVM is a potentially life
      threatening and limb-threatening lesion, especially the 'fistulous' truncular
      form due to its unique embryological and haemodynamic characteristics. AVM
      treatment requires an early aggressive approach, one that is careful and based on
      a thorough assessment of the risks and benefits associated with the treatment
      plan. A successful treatment strategy requires an accurate assessment of the AVM
      taking into account the extent, severity and progression of the lesion. This is
      critical in order to minimize the morbidity associated with the currently
      available therapies. A multidisiciplinary approach that integrates endovascular
      and surgical therapy can substantially improve the treatment results seen in
      patients with AVMs. Preliminary treatment of a fistulous AVM with coil
      embolization is essential in order to minimize associated morbidity and to alter
      the lesion haemodynamics from a high-flow lesion to a low-flow lesion that is
      more amenable to subsequent, definitive management with ethanol or NBCA glue
      embolo/sclerotherapy.

PMID- 19767486
TI  - Popliteal vein compression syndrome: obesity, venous disease and the popliteal
      connection.
AB  - OBJECTIVES: Obesity and venous disease are commonly encountered together. The
      aetiological relationship, however, has not been clear. Popliteal venous
      compression (PVC) has been encountered both on ultrasound and venographically. In
      this study, patients with symptoms and/or signs of chronic venous hypertension
      with PVC were investigated and the relationship to obesity was defined. METHODS:
      A total of 89 patients were included in the study, of which 49 limbs were
      classified as having PVC defined as a greater than 90% reduction in the maximum
      internal diameter (ID) of the popliteal vein (POPV) with knee locking. Forty
      consecutive limbs with venous disease with no evidence of PVC were used as
      controls. The body mass index (BMI) of each group was calculated and the clinical
      symptoms and signs were documented. After the failure of conservative treatment,
      30 of the 49 underwent open popliteal decompression. RESULTS: Patients with PVC
      were found to have a BMI of 34.6 +/- 6.2 compared with 25.3 +/- 3.0 of the
      controls. The POPV ID in the PVC group before and after knee locking changed from
      11.7 +/- 5.0 to 1.0 +/- 2.1 mm, respectively. Postoperatively, the POPV ID before
      and after knee locking changed from 10.2 +/- 2.2 to 9.0 +/- 1.5 mm, respectively.
      At 16.2 +/- 12.1 months follow-up, all the major clinical parameters improved at
      a statistically significant level. CONCLUSIONS: There appears to be a
      relationship between obesity, chronic venous disease and PVC. POPV compression
      syndrome may clarify the previously unexplained venous presentations. Surgical
      decompression provides good results in patients unresponsive to conservative
      treatment.

PMID- 19767487
TI  - Treatment of incompetent perforating veins using the radiofrequency ablation
      stylet: a pilot study.
AB  - BACKGROUND: Although the role of incompetent perforating veins (IPV) in chronic
      venous insufficiency remains controversial, they are often treated by surgical or
      by minimal invasive techniques. OBJECTIVES: To describe the procedure of
      radiofrequency ablation (RFA) of IPV and to evaluate its short-term effectiveness
      and safety. METHODS: In a clinical pilot study, 14 IPV in 12 patients were
      treated with a radiofrequency stylet. After three months, ultrasound (US)
      examination was used to assess anatomical success rate and exclude deep venous
      thrombosis. Also, self-reported side-effects were investigated. RESULTS: Of the
      14 treated IPV, nine (64%) were obliterated on US examination and the others
      showed remaining reflux. Two patients reported localized paresthesia, but no deep
      venous thrombosis was recorded. CONCLUSION: RFA of IPV may be a promising
      procedure, but patient and incompetent perforator vein selection is important and
      further standardization of the procedure is required. Comparative clinical trials
      between RFA and other therapies are warranted.

PMID- 19767488
TI  - Pyoderma gangrenosum; a rare complication of sclerotherapy.
AB  - Pyoderma gangrenosum may develop at sites of minor trauma and in surgical wounds.
      In susceptible people, even minimal trauma or irritation to the skin can result
      in the production of pyoderma gangrenosum lesions. This paper reports an unusual
      case of pyoderma gangrenosum following ultrasound-guided sclerotherapy.

PMID- 19767489
TI  - Lymphoscintigraphy in paediatric patients.

PMID- 19767491
TI  - Health care fraud: physicians as white collar criminals?

PMID- 19767492
TI  - Suicide risk assessment forms: form over substance?

PMID- 19767493
TI  - Symptom patterns related to traumatic exposure among female inmates with and
      without a diagnosis of posttraumatic stress disorder.
AB  - Our study examines the trauma-related experiences of 203 female prison inmates,
      most of whom had experienced chronic trauma throughout their lives but among whom
      only 51 percent met diagnostic criteria for PTSD. We used the two groups to study
      differences in trauma exposure and pre-existent psychopathology as they related
      to the emergence of full diagnostic criteria for PTSD. We also used the entire
      sample to explore the factor structure and endorsement frequencies of each
      symptom category as it related to trauma exposure. Our analyses indicated that
      the PTSD group differed from the non-PTSD group in the number of life traumas
      each group had experienced and the pre-existence of borderline personality
      disorder. Five symptoms accurately differentiated the two groups, with an 86
      percent correct classification: recurrent thoughts, amnesia, loss of interest,
      difficulty concentrating, and a heightened startle response. An exploratory
      factor analysis further suggested two primary factors: intrusion and arousal. We
      apply our findings to the naturalistic versus interactional debate surrounding
      the disorder and reflect on the endorsement frequencies as they might inform our
      understanding of malingering as it occurs in legal and forensic settings.

PMID- 19767494
TI  - Commentary: inadequacy of the categorical approach of the DSM for diagnosing
      female inmates with borderline personality disorder and/or PTSD.
AB  - Warren and her colleagues' timely exploration of the difficulties and
      uncertainties in diagnosing PTSD and personality disorders in the female inmate
      population raises fundamental questions for clinical as well as forensic
      analysis. Questions of under-reporting, over-reporting, and comorbidity in this
      population point to serious inadequacies in the scheme of categorical, context
      independent diagnosis in the Diagnostic and Statistical Manual of Mental
      Disorders. The interplay of predisposition, life history, and current setting and
      circumstances can best be captured by a progressive refining of probability
      estimates. Such a diagnostic process calls for psychodynamically informed
      clinical and forensic interviewing. Additional recommendations are made for the
      purpose of achieving multidimensional, context-sensitive diagnosis and forensic
      evaluation.

PMID- 19767495
TI  - Commentary: trauma and female inmates: why is witnessing more traumatic?
AB  - The study of female inmates by Warren et al. is essential research concerning the
      characteristics of trauma and the symptoms of trauma associated with full PTSD.
      This commentary explores their surprising finding that a high number of female
      inmates who have experienced multiple and severe traumas report that witnessing
      is traumatic and that, in a high percentage, it is associated with full PTSD. The
      commentary proposes a connection between the ultimate finding of Warren et al.
      that the number of traumas predicts full PTSD and links witnessing to symptoms of
      intrusion and arousal via memory formation in individuals with a high incidence
      of lifetime trauma, because of their increased sensitivity.

PMID- 19767496
TI  - POWs versus torturers: forensic evaluation of military personnel.
AB  - In April 2002, 17 American prisoners of war (POWs) and 37 of their family members
      brought an action in federal district court in Washington, D.C., against the
      Republic of Iraq, Saddam Hussein, and the Iraqi Intelligence Service for torture
      the POWs alleged they endured in 1991, following their capture during Operation
      Desert Storm. This action was the first in which prisoners of war sued a
      sovereign state for torture. As part of their case, the plaintiffs claimed
      psychological damage, and presented forensic evaluations of the POWs and their
      families in support. This article will address the novel questions and problems
      in this case, including: the legal context of the action; the logistical
      difficulties in evaluating a large number of plaintiffs in diverse locations; the
      challenges of establishing psychological injury in military personnel; the
      relationship between the forensic findings and the literature on POWs; the
      potential bias and secondary trauma experienced by the examiners; and the outcome
      of the action and prospects for similar actions in the future.

PMID- 19767497
TI  - Commentary: forensic evaluation of military personnel.
AB  - Forensic psychiatric evaluations of military personnel in civil litigation are
      reportedly infrequent. One such case involved former prisoners of war after
      Operation Desert Storm. These evaluations presented many challenges to the
      evaluators with regard to resources and time limitations. Discussion of these
      issues is relevant to forensic evaluations generally.

PMID- 19767498
TI  - False confessions: causes, consequences, and implications.
AB  - In the past two decades, hundreds of convicted prisoners have been exonerated by
      DNA and non-DNA evidence, revealing that police-induced false confessions are a
      leading cause of wrongful conviction of the innocent. In this article, empirical
      research on the causes and correlates of false confessions is reviewed. After a
      description of the three sequential processes that are responsible for the
      elicitation of false confessions--misclassification, coercion, and contamination-
      the three psychologically distinct types of false confession (voluntary,
      compliant, and persuaded) are discussed along with the consequences of
      introducing false-confession evidence in the criminal justice system. The article
      concludes with a brief discussion of the implications of empirical research for
      reducing the number of false confessions and improving the accuracy of confession
      evidence that is introduced against a defendant at trial.

PMID- 19767499
TI  - Commentary: ethics-related implications and neurobiological correlates of false
      confessions in juveniles.
AB  - Forensic psychiatrists typically have no role in the process of obtaining
      confessions. They may believe, as do others, that a confession removes any doubt
      about guilt, but false confessions are not rare. Like the police, forensic
      psychiatrists can inadvertently elicit or solidify a false confession through the
      evaluation process by presuming guilt and forgetting that they are ethically
      obligated to strive for objectivity. Adolescents are at high risk of making false
      confessions because of their immaturity and vulnerability, extrinsic factors
      (such as interrogation techniques), and the dynamic interplay between them.
      Adolescent immaturity can have a direct bearing on a juvenile's appreciation of
      his Miranda rights and his vulnerability to making a confession (or a false
      confession) when exposed to coercive interrogation techniques designed for
      adults. Adolescents need special protection from such interrogation techniques.
      Forensic psychiatrists have an obligation to be alert to the potential for false
      confessions and to avoid compounding the problem by presuming guilt.

PMID- 19767500
TI  - Why does informed consent fail? A discourse analytic approach.
AB  - Informed consent often fails to meet the intended goals that a prospective
      subject should understand fully and choose autonomously to participate in
      research. The current study is an attempt to understand such failures by applying
      linguistic methods of discourse analysis to the transcripts of informed consent
      interviews. Elements of conversation and of the frame of discourse were analyzed
      to understand how the participants shaped their spoken interaction during the
      interview. We looked at the degree to which the subject appeared to be fully
      informed, at the problem of therapeutic misconception, and at the degree to which
      the subject was helped to explore concerns relevant to the choice at hand. We
      found that lapses or miscommunications could be understood specifically in terms
      of conversational elements and framing. This kind of detailed, language-based
      analysis is an alternative to approaches that are more abstract and inferential,
      such as those that are based upon the attitudes or the cognitive performance of
      speakers. We discuss possible educational and research implications of this
      approach.

PMID- 19767501
TI  - Contracting for safety with patients: clinical practice and forensic
      implications.
AB  - The contract for safety is a procedure used in the management of suicidal
      patients and has significant patient care, risk management, and medicolegal
      implications. We conducted a literature review to assess empirical support for
      this procedure and reviewed legal cases in which this practice was employed, to
      examine its effect on outcome. Studies obtained from a PubMed search were
      reviewed and consisted mainly of opinion-based surveys of clinicians and patients
      and retrospective reviews. Overall, empirically based evidence to support the use
      of the contract for safety in any population is very limited, particularly in
      adolescent populations. A legal review revealed that contracting for safety is
      never enough to protect against legal liability and may lead to adverse
      consequences for the clinician and the patient. Contracts should be considered
      for use only in patients who are deemed capable of giving informed consent and,
      even in these circumstances, should be used with caution. A contract should never
      replace a thorough assessment of a patient's suicide risk factors. Further
      empirical research is needed to determine whether contracting for safety merits
      consideration as a future component of the suicide risk assessment.

PMID- 19767502
TI  - Murder-suicide: a review of the recent literature.
AB  - There has been recent widespread media coverage of events that involve murder
      suicide. In this paper, the author does an extensive literature review of studies
      about murder-suicide. The purpose is to determine whether the incidence of murder
      suicide is increasing and what its risk factors are. The results of this review
      show that the incidence of murder-suicide remains at under 0.001%. Risk factors
      for murder-suicide are based on relationship between perpetrator and victims,
      history of domestic violence, sex or perpetrator and victim, age of perpetrator,
      presence of divorce/separation, use of weapon, and history of mental illness.
      This paper shows that the incidence of murder-suicide is low, stable, and similar
      to what has been reported in the past. There are, however, some distinct risk
      factors for murder-suicide including: substance abuse (not as common), mostly
      male perpetrators, depression (more common), and older male caregivers are at
      risk.

PMID- 19767503
TI  - Giving until it hurts?: Altruistic donation of solid organs.
AB  - The increased need for organs has led to greater acceptance of stranger or
      unrelated kidney donation. This broadening of the donor pool introduces
      challenges to the evaluation of such donors. Questions are raised regarding the
      obligation of an evaluator to explore the depth of the donor's intentions. The
      concept of altruism is explored as well as its impact on the consent process.

PMID- 19767504
TI  - Indiana v. Davis: revisiting due process rights of permanently incompetent
      defendants.
AB  - With its landmark Jackson v. Indiana (406 U.S. 715 (1972)) decision, the United
      States Supreme Court ruled that states may not indefinitely confine criminal
      defendants solely on the basis of incompetence to stand trial. While this
      decision led to widespread state statutory and procedural changes, the Jackson
      court left unresolved whether states could indefinitely maintain criminal charges
      against incompetent defendants. Nearly four decades after the Jackson decision,
      the Indiana Supreme Court finally revisited this question in Indiana v. Davis
      (898 N.E.2d. 281 (Ind. 2008)), unanimously ruling that holding criminal charges
      over the head of a permanently incompetent defendant, when her pretrial
      confinement extended beyond the maximum period of any sentence the trial court
      could impose, violated the basic notions of fundamental fairness embodied in the
      Due Process Clause of the Fourteenth Amendment. In this analysis of Indiana v.
      Davis, the facts of the case and the court's rationale for its decision are
      discussed. This unique ruling is considered in light of the questions resolved
      and still unanswered since Jackson v. Indiana.

PMID- 19767505
TI  - Drunk driving, implied consent, and self-incrimination.
AB  - The effects of drunk driving are a significant risk to public health and safety.
      Accordingly, the federal government and the states have enacted laws that permit
      law enforcement to identify offenders and to apply various levels of sanctions.
      There is no constitutional requirement that evidence of drunkenness be permitted
      in defense of criminal behavior. In practice, citizens who undertake to operate
      motor vehicles under the influence of alcohol are considered reckless per se and
      have no right to obstruct law enforcement in determining their condition. Indeed,
      refusal of roadside sobriety tests, including the Breathalyzer, may be considered
      a separate offense. The issuing of Miranda-type warnings by police officers has
      been ruled on recently in New Jersey. In a superior court appellate decision,
      State v. Spell, the court outlined the necessary procedures, concluding that,
      although motorists have no right to refuse testing, police officers have an
      obligation to issue sufficient warnings before the motorist decides how to
      proceed. In the Spell matter, the defendant incriminated himself by refusing the
      testing, even though he was acquitted on the drunk-driving charge. The authors
      discuss the role of expert testimony in these matters.

PMID- 19767506
TI  - Disability guideline, role conflicts, and treatment records.
AB  - The AAPL Practice Guidelines for the Forensic Evaluation of Psychiatric
      Disability reminds treating psychiatrists as well as forensic examiners of the
      potential for role conflicts and of numerous factors related to handling of
      treatment records. This commentary suggests ways of more completely avoiding role
      conflicts, including those related to payment, and elaborates on implementation
      of requirements of the HIPAA Privacy Rules applicable to independent examination
      by third parties.

PMID- 19767507
TI  - The Reader.

PMID- 19767508
TI  - Interim positron emission tomography scans in diffuse large B-cell lymphoma: an
      independent expert nuclear medicine evaluation of the Eastern Cooperative
      Oncology Group E3404 study.
AB  - Positive interim positron emission tomography (PET) scans are thought to be
      associated with inferior outcomes in diffuse large B-cell lymphoma. In the E3404
      diffuse large B-cell lymphoma study, PET scans at baseline and after 3 cycles of
      rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone were
      centrally reviewed by a single reader. To determine the reproducibility of
      interim PET interpretation, an expert panel of 3 external nuclear medicine
      physicians visually scored baseline and interim PET scans independently and were
      blinded to clinical information. The binary Eastern Cooperative Oncology Group
      (ECOG) study criteria were based on modifications of the Harmonization Criteria;
      the London criteria were also applied. Of 38 interim scans, agreement was
      complete in 68% and 71% by ECOG and London criteria, respectively. The range of
      PET(+) interim scans was 16% to 34% (P = not significant) by reviewer. Moderate
      consistency of reviews was observed: kappa statistic = 0.445 using ECOG criteria,
      and kappa statistic = 0.502 using London criteria. These data, showing only
      moderate reproducibility among nuclear medicine experts, indicate the need to
      standardize PET interpretation in research and practice. This trial was
      registered at www.clinicaltrials.gov as #NCT00274924 [corrected].

PMID- 19767509
TI  - Intracranial hemorrhage (ICH) in children with immune thrombocytopenia (ITP):
      study of 40 cases.
AB  - Intracranial hemorrhage (ICH) is a rare but devastating complication of childhood
      immune thrombocytopenia purpura (ITP). A survey of ICH from 1987 to 2000
      identified cases of ICH in childhood ITP in the United States. Forty patients
      with ICH and 80 matched ITP control subjects were accrued. The estimated
      incidence of ICH was 0.19% to 0.78%. Platelet counts were less than 20 x 10(9)/L
      in 90% and less than 10 x 10(9)/L in 75% of children with ICH. Eighteen (45%)
      children developed ICH within 7 days of diagnosis of ITP; for 10 of these, ICH
      was the presenting feature of ITP. Twelve (30%) children had chronic ITP. Head
      trauma and hematuria were the most prominent features associated with ICH,
      identified in 33% and 22.5% of the patients with ICH and 1 and none of the
      controls (both P < .001). Bleeding beyond petechiae and ecchymoses was also
      linked to ICH. Mortality was 25%; a further 25% had neurologic sequelae.
      Strategies by which high-risk children could be identified were considered, and
      the costs of preventive combination treatment were estimated. Children with
      severe thrombocytopenia plus head trauma and/or hematuria appeared to be at
      particularly high risk of ICH. Aggressive treatment of these children may be
      appropriate.

PMID- 19767510
TI  - The thymus-independent immunity conferred by a pneumococcal polysaccharide is
      mediated by long-lived plasma cells.
AB  - It was recently shown that bacterial thymus-independent (TI) antigens confer long
      lasting immunity and generate memory B lymphocytes. However, reactivation of TI
      memory B cells is repressed in immunocompetent mice, thus raising the issue of
      the mechanism whereby TI vaccines confer immune protection. Here, we propose an
      explanation to this apparent paradox by showing that a Streptococcus pneumoniae
      capsular polysaccharide (PS) generates long-lived bone marrow (BM) plasma cells
      which frequency can be increased by CpG oligodeoxynucleotides (ODNs). The
      adjuvant effect of CpG ODNs on the PS3 Ab response is directly targeted to B
      cells and does not involve B-1a cells. We also demonstrated that BM plasma cells
      generated in response to the thymus-dependent (TD) form of the PS vaccine have a
      higher secretion capacity than those produced after immunization with the CpG
      adjuvanted PS vaccine. Finally, we show that the PS-specific BM plasma cell
      compartment is sufficient to confer full protection of vaccinated mice against S
      pneumoniae infection. Altogether, our results show that TI antigens like their TD
      counterparts can generate both the lymphoid and the plasma cell component of B
      cell memory. They also provide a framework for the improvement and widespread
      usage of TI vaccines.

PMID- 19767511
TI  - Homeostasis of dendritic cells in lymphoid organs is controlled by regulation of
      their precursors via a feedback loop.
AB  - Dendritic cells (DCs) are key coordinators of the immune response, governing the
      choice between tolerance and immunity. Despite their importance, the mechanisms
      controlling the size of the DC compartment are largely unknown. Using a mouse
      model allowing continuous DC depletion, we show that maintenance of DC numbers in
      spleen is an active process mediated by Flt3-L-dependent regulation of precursor
      differentiation into DCs, rather than by changes in proliferation of the
      differentiated DCs. In particular, the frequency and differentiation potential of
      intrasplenic DC precursors increased in response to reduced DC numbers. Levels of
      Flt3-L, a cytokine required for DC differentiation, increased in the blood after
      DC depletion and returned to normal levels once the DC compartment filled up
      again. Our data suggest a feedback regulation of DC homeostasis whereby reduction
      of the DC pool size promotes differentiation of their precursors, via increased
      Flt3-L availability. This mechanism is different to those known for other immune
      cell types, such as the B- and T-cell compartments, whereby lymphopenia induces
      proliferation of already differentiated lymphocytes.

PMID- 19767512
TI  - Prediction of osteoporosis with dental radiographs and age.
AB  - OBJECTIVES: In this study age and the trabecular pattern present on dental
      radiographs were used to predict the presence of osteoporosis. The objective was
      to evaluate the contribution of the trabecular pattern to the prediction.
      METHODS: In this project, 671 women between 45 and 71 years of age were
      recruited. Medical history was obtained and dental radiographs were made. Bone
      mineral density (BMD) was measured at three sites to assess the presence of
      osteoporosis according to the World Health Organization criteria. The radiographs
      were subjected to image analysis methods yielding measurements of the trabecular
      pattern. Thereafter, discriminant analysis was used to predict the presence of
      osteoporosis by means of the trabecular pattern and age. Sensitivity and
      specificity of age and the trabecular pattern were compared. Also, it was checked
      whether the inclusion of the trabecular pattern improved the sensitivity and
      specificity that were obtained when only age was used as the predictor. RESULTS:
      The sensitivity and specificity of the trabecular pattern present on dental
      radiographs were almost equal to those of age. However, combining age with the
      trabecular pattern increased the sensitivity from 0.71 to 0.75 and the
      specificity from 0.72 to 0.78; the latter increase was statistically significant.
      CONCLUSIONS: The trabecular pattern predicts the presence of osteoporosis just as
      well as age does. When combining the trabecular pattern with age, the sensitivity
      and specificity increased. Only the latter increase was statistically
      significant.

PMID- 19767513
TI  - Evaluation of periapical changes following endodontic therapy: digital
      subtraction technique compared with computerized morphometric analysis.
AB  - OBJECTIVES: The aim of this study was to compare two methods for the evaluation
      of periapical lesion changes following endodontic therapy (digital subtraction
      technique and morphometric analysis) by outlining the radiolucent area. METHODS:
      13 human anterior teeth with pulp necrosis and chronic periapical lesions were
      used. Periapical radiographs were taken immediately after endodontic therapy (0)
      and then 2 months, 4 months and 6 months post treatment, using an intraoral
      radiographic film holder stabilized with impression material. The films were
      processed in a standard manner and the digitized images were submitted to digital
      subtraction using Adobe Photoshop 6.0. New bone formation or bone resorption
      areas were then measured. In the morphometric analysis, the periapical lesions
      were outlined using VixWin 2000 and the area (in square millimetres) was
      recorded. The obtained data were submitted to agreement analysis for comparison
      of the two techniques. RESULTS: There was no correlation between the areas of
      radiographic changes detected by digital subtraction and periapical lesion
      outline (r = 0.02-0.45). The new bone formation areas observed by digital
      subtraction presented higher values, with bone changes being especially evident
      in the 2 month follow-up radiographs, which suggests a higher sensitivity for
      this method. CONCLUSIONS: Both methods are suitable for the evaluation of
      periapical lesion changes, but the digital subtraction technique is more
      sensitive for detecting radiographic periapical changes.

PMID- 19767514
TI  - A comparative study of high-resolution cone beam computed tomography and charge
      coupled device sensors for detecting caries.
AB  - OBJECTIVES: Conventional radiographic imaging of teeth underestimates the
      presence of caries. The objective of this study was to compare the efficacy of
      high-resolution cone beam CT (CBCT) images and conventional charge-coupled device
      (CCD) images for detecting proximal and occlusal caries. METHODS: Non-restored,
      extracted human permanent premolar and molar teeth were mounted and then imaged
      with a 3DX Accuitomo and a CCD. We selected 92 occlusal and 100 proximal surfaces
      for raters to score. Of these, 36 and 25, respectively, had lesions extending
      into dentin. Using a five-step confidence scale, eight practising dentists
      evaluated the images for the presence of caries in dentin using both modalities.
      Actual presence and extent of caries was established with microCT imaging.
      RESULTS: For proximal surface lesions extending into dentin, the average
      sensitivity score using 3DX images (0.61) was almost twice that of CCD images
      (0.33) and the difference was significant. The specificity values for both
      systems were high and not significantly different from each other. For occlusal
      surfaces, raters detected significantly more lesions in the enamel or dentin when
      using the 3DX images than when using CCD images. However, the raters also had
      significantly lower average specificity scores for the 3DX images compared with
      the CCD images for lesions at both depths. CONCLUSIONS: Practising dentists were
      able to improve their detection of proximal-surface caries extending into the
      dentin, but not occlusal caries, using 3DX high-resolution cone beam CT images
      compared with CCD images.

PMID- 19767515
TI  - Comparison of visual inspection and different radiographic methods for dentin
      caries detection on occlusal surfaces.
AB  - OBJECTIVES: The aim of the present study was to assess the validity of the
      digital phosphor plate radiographic technique (Gendex Dental Systems) on occlusal
      surfaces in comparison with visual examination and conventional E- and F-speed
      films. METHODS: The study material consisted of 54 non-cavitated third molars
      with a range of appearances, including apparently sound surfaces. Each surface
      was visually examined (VI) according to the criteria established by Ekstrand et
      al. Three radiographic images (E-speed, F-speed, digital phosphor plate film)
      were taken of each molar. The standardized radiograph technique used an alignment
      fixture to reproduce the focus-to-object distance as well as the object-to-film
      distance. Afterwards each tooth was cut into sections in the buccolingual
      direction with a microtome saw, and caries extension was assessed using light
      microscopy (LM) and microradiography (MR). The statistical analysis included the
      calculation of sensitivity (SE), specificity (SP) and A(z) values. RESULTS: The
      following validity parameters were found for the tested diagnostic methods on the
      dentin caries level: VI/LM, 68.0 SE/93.1 SP/0.698 A(z); VI/MR, 68.2/87.5/0.751; E
      speed/LM, 76.0/78.6/0.637; E-speed/MR, 77.3/74.2/0.681; F-speed/LM,
      64.0/67.9/0.507; F-speed/MR, 68.2/67.7/0.594; Gendex/LM, 60.0/85.7/0.629; and
      Gendex/MR, 59.1/80.6/0.586. CONCLUSION: The methods used showed different levels
      of validity: E- and F-speed films were linked to higher sensitivity values,
      whereas a higher specificity was recorded for the tested imaging plate system. In
      accordance with the diagnostic performance, the digital system can be recommended
      for practical use and potentially help prevent overtreatment thanks to its high
      SP.

PMID- 19767516
TI  - Detectability of chemically induced periapical lesions by limited cone beam
      computed tomography, intra-oral digital and conventional film radiography.
AB  - OBJECTIVE: Our aim was to compare the Accu-I-Tomo (3DX), the Digora Optime image
      plate system and F-speed film in detecting chemically created apical lesions.
      METHODS: Lesions were created by applying perchloric acid apical to extracted
      teeth in jaw specimens for 1, 1.5 or 2 h. After being repositioned, teeth were
      radiographed with Accu-I-Tomo limited cone beam CT (LCBCT), Digora Optime storage
      phosphor plates (SPP) and F-speed films. Six observers scored the presence of
      lesions using a five-grade scale. The accuracy of each observer and modality was
      assessed through receiver operating characteristic (ROC) analysis and A(z) values
      were compared using two-way ANOVA. Pairwise comparisons of imaging systems were
      carried out using the Mann-Whitney U-test. Differences in A(z) values were
      compared using Friedman and Dunn's tests. Kappa (kappa) was used to measure
      interobserver agreement. RESULTS: The A(z) values were larger for LCBCT than for
      SPP and film for all acid durations. For 1 h of acid duration a significant
      difference was found between LCBCT and film (P = 0.02) and between LCBCT and SPP
      (P = 0.0043), For 1.5 h a significant difference (P = 0.006) was found between
      LCBCT and SPP only. For 2 h acid duration, there was no significant difference
      between LCBCT and film or SPP (P>0.05). Between SPP and film no significant
      difference was found for any acid duration (P>0.05). kappa ranged between fair
      and moderate for LCBCT and between slight and fair for SPP and film. CONCLUSION:
      LCBCT images provided better than or similar detectability as film and SPP images
      of chemically created periapical lesions.

PMID- 19767517
TI  - Diagnostic accuracy of microcomputed tomography for osseous abnormalities in the
      rat temporomandibular joint condyle.
AB  - OBJECTIVES: Our aim was to investigate the diagnostic accuracy of in vivo micro
      CT for osseous abnormalities of the rat temporomandibular joint (TMJ) condyle,
      using macroscopic observations as the "gold standard". METHODS: A 30 TMJ
      arthritis model was prepared by injecting inflammatory complete Freund's adjuvant
      (CFA) into one side of the TMJ cavities of rats. The TMJ condyles were then
      imaged using micro-CT. The samples were macroscopically evaluated for osseous
      abnormalities, including erosions, osteophytes, flattening and concavity. The
      micro-CT images were independently assessed for abnormalities using the same
      criteria. Images in three planes were produced using the micro-XYZ technique with
      the micro-CT equipment. RESULTS: According to the macroscopic observations, 26 of
      the 60 rat condyles showed osseous abnormalities. The micro-XYZ images detected
      abnormalities in 25 of the condyles. The condyle diagnostic accuracy of micro-CT
      was 0.98, the sensitivity was 0.96 and the specificity was 1.0. CONCLUSIONS: Good
      diagnostic results were obtained using micro-CT. It is therefore an effective
      technique for the evaluation of osseous abnormalities in the rat TMJ condyle.

PMID- 19767518
TI  - Effect of magnetic resonance imaging on microleakage of amalgam restorations: an
      in vitro study.
AB  - OBJECTIVES: The technique of MRI, using powerful magnets, plays an important role
      in the diagnosis of diseases of the head and neck without any ionizing radiation.
      Because of the potential hazard imposed by the presence of ferromagnetic metals,
      patients with implanted metallic objects are excluded from MRI. However, amalgam
      restorations seem to be safe. The purpose of this study was to evaluate
      microleakage of amalgam restorations following MRI. METHODS: 63 human freshly
      extracted premolars were divided into 3 groups based on 3 high-copper amalgams
      used to restore standard class V preparations on both buccal and lingual
      surfaces. Three different amalgam materials were used: Cinalux, GS-80 and
      Vivacap. The teeth were transferred into saline solution for 2 months at room
      temperature and then sectioned mesiodistally. MRI was randomly applied to one
      half of each section, and the other half was kept as a control. Following MRI,
      all specimens were immersed in a dye solution, sectioned and scored for any
      microleakage using a stereomicroscope. RESULTS: Differences in microleakage
      within each group following MRI were significant in the GS-80 and Vivacap groups
      but not in the Cinalux group. However, there was no significant difference
      between the three groups regarding the microleakage score. CONCLUSIONS: The
      results of this study suggest that MRI is not a completely safe technique in
      patients with amalgam restorations. It was shown that the main effect of fields
      led to the appearance of thermoelectromagnetic convection, which is responsible
      for the enhancement of the diffusion process, grain boundary migration and
      vacancy formation resulting in microleakage.

PMID- 19767519
TI  - The occurrence of keratocystic odontogenic tumours in nevoid basal cell carcinoma
      syndrome.
AB  - OBJECTIVES: This retrospective study reviews the occurrence of keratocystic
      odontogenic tumours (KOTs) in nevoid basal cell carcinoma syndrome (NBCCS)
      patients seen in the Oral and Maxillofacial Radiology Special Procedures Clinic
      in the Faculty of Dentistry at the University of Toronto. METHODS: This study
      examines the number and radiographic features of KOTs identified in 11 NBCCS
      patients who presented with 43 KOTs between January 1989 and 30 June 2007 on
      plain film radiographs and CT. RESULTS: Regression analysis revealed a
      statistically significant (P < 0.01) relationship between the age at first KOT
      occurrence and the total number of lifetime KOTs (r = -0.78). Of the KOTs
      identified, 25 developed in the mandible and 18 developed in the maxillae. The
      majority of these were associated with a change in either the size or shape of
      the follicular space, and both plain film radiography and CT were equally
      effective at demonstrating these changes. CT was, however, more effective at
      demonstrating endosteal scalloping of cortical bone than plain film radiography
      (P < 0.001) while the opposite was true for showing tooth displacement (P <
      0.01). For patients imaged with both plain radiography and CT (29 KOTs), 5 KOTs
      were detectable only by CT. CONCLUSIONS: Our results suggest that there should be
      early and frequent monitoring of NBCCS patients for the development of KOTs in
      youth and adolescence, and that CT imaging should play an important role in these
      investigations.

PMID- 19767520
TI  - Prevalence and risk factors of mucous retention cysts in a Brazilian population.
AB  - OBJECTIVES: The aim of this study was to estimate the prevalence and analyse the
      risk factors of mucous retention cysts (MRCs) of the maxillary sinus. METHODS:
      From November 2002 to May 2007, 6293 panoramic radiographs were taken and
      retrospectively reviewed to estimate the prevalence of MRCs and to analyse risk
      factors (month, relative air humidity and mean temperature). The months in which
      MRCs occurred were recorded and analysed. The Spearman rank correlation
      coefficient was used to correlate MRCs with relative air humidity, environmental
      temperature and month (significance level R(2)>0.85). RESULTS: Of the 6293
      radiographs analysed, 201 (3.19%) images were suggestive of MRCs. No significant
      correlation was found between MRCs and relative humidity (R(2) = 0.15) of the air
      or temperature (R(2) = 0.40). The months with the highest numbers of MRC cases
      were September, October and November. CONCLUSIONS: The prevalence of MRCs was
      low, and no statistical correlation was found between MRCs and relative humidity
      of the air, mean temperature or month.

PMID- 19767521
TI  - Patient comfort in periapical examination using digital receptors.
AB  - OBJECTIVES: The aim of this study was to compare digital and conventional
      radiography with regard to patient comfort during periapical radiographic
      examination. METHODS: 300 patients were submitted to a simulation of a
      radiographic periapical examination of a dentate region using conventional
      intraoral radiographic film (Kodak Insight) with and without the use of an RINN
      film holder, a Schick charge-coupled device (CCD) sensor, a Visualix CCD sensor
      and a Denoptix phosphor plate. The patients were asked to score how they felt in
      terms of comfort on a 100 mm visual analogue scale. The Wilcoxon test (alpha =
      0.05) was applied to compare the comfort score of different types of imaging
      receptor from each simulated radiographic region reported by the patients.
      RESULTS: The median of the "comfort data" according to the type of imaging
      receptor was 40 mm for conventional intraoral radiographic film with the use of
      the film holder, 85 mm for conventional intraoral radiographic film without the
      film holder, 80 mm for Schick and Visualix receptors, and 90 mm for the Denoptix
      receptor. CONCLUSIONS: Denoptix was the most comfortable imaging receptor,
      followed in decreasing order by Schick and Visualix, conventional intraoral
      radiographic film without using the film holder and conventional intraoral
      radiographic film with a film holder.

PMID- 19767522
TI  - Osseous choristoma of the submandibular region: case report.
AB  - This report presents a case of osseous choristoma in the submandibular region of
      a 33-year-old female. Her chief complaint was painless swelling in the
      submandibular region. Panoramic radiography showed a well-defined, round,
      radiopaque lesion near the inferior border of the right mandibular angle. Coronal
      and sagittal tomographic images indicated a high-density area in the right
      submandibular region with no bony connection. The lesion was diagnosed as an
      osseous choristoma based on histopathological examination of the surgical
      specimen. A 1-year follow-up period was uneventful.

PMID- 19767523
TI  - Author's reply to the Letter to the Editor entitled "Gold standard for the
      comparison of the diagnostic accuracy of panoramic images for approximal caries
      detection" published in Dentomaxillofacial Radiology (2009;38:245).

PMID- 19767525
TI  - Pyruvate-fortified cardioplegia evokes myocardial erythropoietin signaling in
      swine undergoing cardiopulmonary bypass.
AB  - Pyruvate-fortified cardioplegia protects myocardium and hastens postsurgical
      recovery of patients undergoing cardiopulmonary bypass (CPB). Pyruvate reportedly
      suppresses degradation of the alpha-subunit of hypoxia-inducible factor-1 (HIF
      1), an activator of the gene encoding the cardioprotective cytokine
      erythropoietin (EPO). This study tested the hypothesis that pyruvate-enriched
      cardioplegia evoked EPO expression and mobilized EPO signaling mechanisms in
      myocardium. Hearts of pigs maintained on CPB were arrested for 60 min with 4:1
      blood-crystalloid cardioplegia. The crystalloid component contained 188 mM
      glucose + or - 24 mM pyruvate. After 30-min cardiac reperfusion with cardioplegia
      free blood, the pigs were weaned from CPB. Left ventricular myocardium was
      sampled 4 h after CPB for immunoblot assessment of HIF-1alpha, EPO and its
      receptor, the signaling kinases Akt and ERK, and endothelial nitric oxide
      synthase (eNOS), an effector of EPO signaling. Pyruvate-fortified cardioplegia
      stabilized arterial pressure post-CPB, induced myocardial EPO mRNA expression,
      and increased HIF-1alpha, EPO, and EPO-R protein contents by 60, 58, and 123%,
      respectively, vs. control cardioplegia (P < 0.05). Pyruvate cardioplegia also
      increased ERK phosphorylation by 61 and 118%, respectively, vs. control
      cardioplegia-treated and non-CPB sham myocardium (P < 0.01), but did not alter
      Akt phosphorylation. Nitric oxide synthase (NOS) activity and eNOS content fell
      32% following control CPB vs. sham, but pyruvate cardioplegia prevented these
      declines, yielding 49 and 80% greater NOS activity and eNOS content vs.
      respective control values (P < 0.01). Pyruvate-fortified cardioplegia induced
      myocardial EPO expression and mobilized the EPO-ERK-eNOS mechanism. By
      stabilizing HIF-1alpha, pyruvate-fortified cardioplegia may evoke sustained
      activation of EPO's cardioprotective signaling cascade in myocardium.

PMID- 19767526
TI  - Pathways to embryonic heart failure.

PMID- 19767527
TI  - Antioxidants and aging: NMR-based evidence of improved skeletal muscle perfusion
      and energetics.
AB  - We sought to examine the potential role of oxidative stress on skeletal muscle
      function with advancing age. Nuclear magnetic resonance (NMR) was employed to
      simultaneously assess muscle perfusion (arterial spin labeling) and energetics
      ((31)P NMR spectroscopy) in the lower leg of young (26 + or - 5 yr, n = 6) and
      older (70 + or - 5 yr, n = 6) healthy volunteers following the consumption of
      either placebo (PL) or an oral antioxidant (AO) cocktail (vitamins C and E and
      alpha-lipoic acid), previously documented to decrease plasma free radical
      concentration. NMR measurements were made during and after 5 min of moderate
      intensity (approximately 5 W) plantar flexion exercise. AO administration
      significantly improved end-exercise perfusion (AO, 50 + or - 5, and PL, 43 + or -
      4 ml x 100 g(-1) x min(-1)) and postexercise perfusion area under the curve (AO,
      1,286 + or - 236, and PL, 866 + or - 144 ml/100 g) in older subjects, whereas AO
      administration did not alter hemodynamics in the young group. Concomitantly,
      muscle oxidative capacity (time constant of phosphocreatine recovery, tau) was
      improved following AO in the older (AO, 43 + or - 1, and PL, 51 + or - 7 s) but
      not the young (AO, 54 + or - 5, and PL, 48 + or - 7 s) group. These findings
      support the concept that oxidative stress may be partially responsible for the
      age-related decline in skeletal muscle perfusion during physical activity and
      reveal a muscle metabolic reserve capacity in the elderly that is accessible
      under conditions of improved perfusion.

PMID- 19767528
TI  - Endogenous regulation of cardiovascular function by apelin-APJ.
AB  - Studies have shown significant cardiovascular effects of exogenous apelin
      administration, including the potent activation of cardiac contraction. However,
      the role of the endogenous apelin-APJ pathway is less clear. To study the loss of
      endogenous apelin-APJ signaling, we generated mice lacking either the ligand
      (apelin) or the receptor (APJ). Apelin-deficient mice were viable, fertile, and
      showed normal development. In contrast, APJ-deficient mice were not born in the
      expected Mendelian ratio, and many showed cardiovascular developmental defects.
      Under basal conditions, both apelin and APJ null mice that survived to adulthood
      manifested modest decrements in contractile function. However, with exercise
      stress both mutant lines demonstrated consistent and striking decreases in
      exercise capacity. To explain these findings, we explored the role of autocrine
      signaling in vitro using field stimulation of isolated left ventricular
      cardiomyocytes lacking either apelin or APJ. Both groups manifested less
      sarcomeric shortening and impaired velocity of contraction and relaxation with no
      difference in calcium transient. Taken together, these results demonstrate that
      endogenous apelin-APJ signaling plays a modest role in maintaining basal cardiac
      function in adult mice with a more substantive role during conditions of stress.
      In addition, an autocrine pathway seems to exist in myocardial cells, the
      ablation of which reduces cellular contraction without change in calcium
      transient. Finally, differences in the developmental phenotype between apelin and
      APJ null mice suggest the possibility of undiscovered APJ ligands or ligand
      independent effects of APJ.

PMID- 19767529
TI  - A high-fat diet increases adiposity but maintains mitochondrial oxidative enzymes
      without affecting development of heart failure with pressure overload.
AB  - A high-fat diet can increase adiposity, leptin secretion, and plasma fatty acid
      concentration. In hypertension, this scenario may accelerate cardiac hypertrophy
      and development of heart failure but could be protective by activating peroxisome
      proliferator-activated receptors and expression of mitochondrial oxidative
      enzymes. We assessed the effects of a high-fat diet on the development of left
      ventricular hypertrophy, remodeling, contractile dysfunction, and the activity of
      mitochondrial oxidative enzymes. Mice (n = 10-12/group) underwent transverse
      aortic constriction (TAC) or sham surgery and were fed either a low-fat diet (10%
      of energy intake as fat) or a high-fat diet (45% fat) for 6 wk. The high-fat diet
      increased adipose tissue mass and plasma leptin and insulin. Left ventricular
      mass and chamber size were unaffected by diet in sham animals. TAC increased left
      ventricular mass (approximately 70%) and end-systolic and end-diastolic areas
      (approximately 100% and approximately 45%, respectively) to the same extent in
      both dietary groups. The high-fat diet increased plasma free fatty acid
      concentration and prevented the decline in the activity of the mitochondrial
      enzymes medium chain acyl-coenzyme A dehydrogenase (MCAD) and citrate synthase
      that was observed with TAC animals on a low-fat diet. In conclusion, a high-fat
      diet did not worsen cardiac hypertrophy or left ventricular chamber enlargement
      despite increases in fat mass and insulin and leptin concentrations. Furthermore,
      a high-fat diet preserved MCAD and citrate synthase activities during pressure
      overload, suggesting that it may help maintain mitochondrial oxidative capacity
      in failing myocardium.

PMID- 19767530
TI  - Increased susceptibility of aged hearts to ventricular fibrillation during
      oxidative stress.
AB  - Oxidative stress with hydrogen peroxide (H(2)O(2)) readily promotes early
      afterdepolarizations (EADs) and triggered activity (TA) in isolated rat and
      rabbit ventricular myocytes. Here we examined the effects of H(2)O(2) on
      arrhythmias in intact Langendorff rat and rabbit hearts using dual-membrane
      voltage and intracellular calcium optical mapping and glass microelectrode
      recordings. Young adult rat (3-5 mo, N = 25) and rabbit (3-5 mo, N = 6) hearts
      exhibited no arrhythmias when perfused with H(2)O(2) (0.1-2 mM) for up to 3 h.
      However, in 33 out of 35 (94%) aged (24-26 mo) rat hearts, 0.1 mM H(2)O(2) caused
      EAD-mediated TA, leading to ventricular tachycardia (VT) and fibrillation (VF).
      Aged rabbits (life span, 8-12 yr) were not available, but 4 of 10 middle-aged
      rabbits (3-5 yr) developed EADs, TA, VT, and VF. These arrhythmias were
      suppressed by the reducing agent N-acetylcysteine (2 mM) and CaMKII inhibitor KN
      93 (1 microM) but not by its inactive form (KN-92, 1 microM). There were no
      significant differences between action potential duration (APD) or APD
      restitution slope before or after H(2)O(2) in aged or young adult rat hearts. In
      histological sections, however, trichrome staining revealed that aged rat hearts
      exhibited extensive fibrosis, ranging from 10-90%; middle-aged rabbit hearts had
      less fibrosis (5-35%), whereas young adult rat and rabbit hearts had <4%
      fibrosis. In aged rat hearts, EADs and TA arose most frequently (70%) from the
      left ventricular base where fibrosis was intermediate ( approximately 30%).
      Computer simulations in two-dimensional tissue incorporating variable degrees of
      fibrosis showed that intermediate (but not mild or severe) fibrosis promoted EADs
      and TA. We conclude that in aged ventricles exposed to oxidative stress, fibrosis
      facilitates the ability of cellular EADs to emerge and generate TA, VT, and VF at
      the tissue level.

PMID- 19767531
TI  - eNOS uncoupling and endothelial dysfunction in aged vessels.
AB  - Endothelial nitric oxide synthase (eNOS) uncoupling is a mechanism that leads to
      endothelial dysfunction. Previously, we reported that shear stress-induced
      release of nitric oxide in vessels of aged rats was significantly reduced and was
      accompanied by increased production of superoxide (18, 27). In the present study,
      we investigated the influence of aging on eNOS uncoupling. Mesenteric arteries
      were isolated from young (3 mo) and aged (24 mo) C57 BL/6J mice. The expression
      of eNOS protein in young vs. aged mice was not significantly different. However,
      the aged mice had remarkable increases in the ratio of eNOS monomers to dimers
      and N(omega)-nitro-l-arginine methyl ester-inhibitable superoxide formation. The
      level of nitrotyrosine in the total protein and precipitated eNOS of aged vessels
      was increased compared with that in young vessels. HPLC analysis indicated a
      reduced level of tetrahydrobiopterin (BH4), an essential cofactor for eNOS, in
      the mesenteric arteries of aged mice. Quantitative PCR results implied that the
      diminished BH4 may result from the decreased expressions of GTP cyclohydrolase I
      and sepiapterin reductase, enzymes involved in BH4 biosynthesis. When isolated
      and cannulated second-order mesenteric arteries (approximately 150 microm) from
      aged mice were treated with sepiapterin, acetylcholine-induced, endothelium
      dependent vasodilation improved significantly, which was accompanied by
      stabilization of the eNOS dimer. These data suggest that eNOS uncoupling and
      increased nitrosylation of eNOS, decreased expressions of GTP cyclohydrolase I
      and sepiapterin reductase, and subsequent reduced BH4 bioavailability may be
      important contributors of endothelial dysfunction in aged vessels.

PMID- 19767532
TI  - Ranolazine, an antianginal agent, markedly reduces ventricular arrhythmias
      induced by ischemia and ischemia-reperfusion.
AB  - We tested the effect of the antianginal agent ranolazine on ventricular
      arrhythmias in an ischemic model using two protocols. In protocol 1, anesthetized
      rats received either vehicle or ranolazine (10 mg/kg, iv bolus) and were
      subjected to 5 min of left coronary artery (LCA) occlusion and 5 min of
      reperfusion with electrocardiogram and blood pressure monitoring. In protocol 2,
      rats received either vehicle or three doses of ranolazine (iv bolus followed by
      infusion) and 20 min of LCA occlusion. With protocol 1, ventricular tachycardia
      (VT) occurred in 9/12 (75%) vehicle-treated rats and 1/11 (9%) ranolazine-treated
      rats during reperfusion (P = 0.003). Sustained VT occurred in 5/12 (42%) vehicle
      treated but 0/11 in ranolazine-treated rats (P = 0.037). The median number of
      episodes of VT during reperfusion in vehicle and ranolazine groups was 5.5 and 0,
      respectively (P = 0.0006); median duration of VT was 22.2 and 0 s in vehicle and
      ranolazine rats, respectively (P = 0.0006). With protocol 2, mortality in the
      vehicle group was 42 vs. 17% (P = 0.371), 10% (P = 0.162) and 0% (P = 0.0373)
      with ranolazine at plasma concentrations of 2, 4, and 8 microM, respectively.
      Ranolazine significantly reduced the incidence of ventricular fibrillation [67%
      in controls vs. 42% (P = 0.414), 30% (P = 0.198) and 8% (P = 0.0094) in
      ranolazine at 2, 4, and 8 microM, respectively]. Median number (2.5 vs. 0; P =
      0.0431) of sustained VT episodes, incidence of sustained VT (83 vs. 33%, P =
      0.0361), and the duration of VT per animal (159 vs. 19 s; P = 0.0410) were also
      significantly reduced by ranolazine at 8 microM. Ranolazine markedly reduced
      ischemia-reperfusion induced ventricular arrhythmias. Ranolazine demonstrated
      promising anti-arrhythmic properties that warrant further investigation.

PMID- 19767533
TI  - siRNA-mediated knockdown of h-caldesmon in vascular smooth muscle.
AB  - Smooth muscle contraction involves phosphorylation of the regulatory myosin light
      chain. However, this thick-filament system of regulation cannot account for all
      aspects of a smooth muscle contraction. An alternate site of contractile
      regulation may be in the thin-filament-associated proteins, in particular
      caldesmon. Caldesmon has been proposed to be an inhibitory protein that acts
      either as a brake to stop any increase in resting or basal tone, or as a
      modulatory protein during contraction. The goal of this study was to use short
      interfering RNA technology to decrease the levels of the smooth muscle-specific
      isoform of caldesmon in intact vascular smooth muscle tissue to determine more
      carefully what role(s) caldesmon has in smooth muscle regulation. Intact strips
      of vascular tissue depleted of caldesmon produced significant levels of
      shortening velocity, indicative of cross-bridge cycling, in the unstimulated
      tissue and exhibited lower levels of contractile force to histamine. Our results
      also suggest that caldesmon does not play a role in the cooperative activation of
      unphosphorylated cross bridges by phosphorylated cross bridges. The velocity of
      shortening of the constitutively active tissue and the high basal values of
      myosin light chain phosphorylation suggest that h-caldesmon in vivo acts as a
      brake against contractions due to basally phosphorylated myosin. It is also
      possible that phosphorylation of h-caldesmon alone in the resting state may be a
      mechanism to produce increases in force without stimulation and increases in
      calcium. Disinhibition of h-caldesmon by phosphorylation would then allow force
      to be developed by activated myosin in the resting state.

PMID- 19767534
TI  - Quantitative analysis of phospholipids containing arachidonate and
      docosahexaenoate chains in microdissected regions of mouse brain.
AB  - Phospholipids containing polyunsaturated fatty acyl chains are prevalent among
      brain lipids, and regional differences in acyl chain distribution appear to have
      both functional and pathological significance. A method is described in which the
      combined application of GC and multiple reaction monitoring (MRM) MS yielded
      precise relative quantitation and approximate absolute quantitation of lipid
      species containing a particular fatty acyl chain in milligram-sized tissue
      samples. The method uses targeted MRM to identify specific molecular species of
      glycerophosphocholine lipids, glycerophospho-ethanolamine lipids,
      glycerophosphoinositol lipids, glycerophosphoserine lipids, glycero
      phosphoglycerol lipids, and phosphatidic acids that contain esterified
      arachidonate (AA) and docosahexaenoate (DHA) separated during normal phase
      LC/MS/MS analysis. Quantitative analysis of the AA and DHA in the LC fractions is
      carried out using negative ion chemical ionization GC/MS and stable isotope
      dilution strategies. The method has been applied to assess the
      glycerophospholipid molecular species containing AA and DHA in microdissected
      samples of murine cerebral cortex and hippocampus. Results demonstrate the
      potential of this approach to identify regional differences in phospholipid
      concentration and reveal differences in specific phospholipid species between
      cortex and hippocampus. These differences may be related to the differential
      susceptibility of different brain regions to neurodegenerative disorders.

PMID- 19767535
TI  - Apolipoprotein M expression increases the size of nascent pre beta HDL formed by
      ATP binding cassette transporter A1.
AB  - Apolipoprotein M (apoM) is a novel apolipoprotein that is reportedly necessary
      for pre beta HDL formation; however, its detailed function remains unknown. We
      investigated the biogenesis and properties of apoM and its effects on the initial
      steps of nascent pre beta HDL assembly by ABCA1 in HEK293 cells. Transiently
      transfected apoM was localized primarily in the endomembrane compartment. Pulse
      chase analyses demonstrated that apoM is inefficiently secreted, relative to
      human serum albumin, and that approximately 50% remains membrane-associated after
      extraction with sodium carbonate, pH 11.5. To investigate the role of apoM in
      nascent pre beta HDL formation, ABCA1-expressing or control cells, transfected
      with empty vector, apoM, or C-terminal epitope-tagged apoM (apoM-C-FLAG), were
      incubated with (125)I-apoA-I for 24 h. Conditioned media were harvested and
      fractionated by fast-protein liquid chromatography (FPLC) to monitor HDL particle
      size. Pre beta HDL particles were formed effectively in the absence of apoM
      expression; however, increased apoM expression stimulated the formation of larger
      sized nascent pre beta HDLs. Immunoprecipitation with anti-apoA-I antibody
      followed by apoM Western blot analysis revealed that little secreted apoM was
      physically associated with pre beta HDL. Our results suggest that apoM is an
      atypical secretory protein that is not necessary for ABCA1-dependent pre beta HDL
      formation but does stimulate the formation of larger-sized pre beta HDL. We
      propose that apoM may function catalytically at an intracellular site to transfer
      lipid onto pre beta HDL during or after their formation by ABCA1.

PMID- 19767536
TI  - Patellar height and tibial slope after opening-wedge proximal tibial osteotomy: a
      prospective study.
AB  - BACKGROUND: Further knee surgery after proximal tibial osteotomies has been
      reported to have a more difficult surgical exposure due to decreased patellar
      height after the osteotomy. Although a decrease in patellar height has been
      reported for closing-wedge proximal tibial osteotomies, it has not been widely
      verified among opening-wedge procedures. HYPOTHESIS: A significant decrease in
      patellar height would result after opening-wedge proximal tibial osteotomies and
      a postoperative change in tibial slope would also result, depending on the medial
      tibial plate position, which would affect patellar height. STUDY DESIGN: Case
      series; Level of evidence, 4. METHODS: Patients (n = 129) who underwent opening
      wedge proximal tibial osteotomies (n = 130) were prospectively followed. Patellar
      height was calculated for preoperative lateral knee radiographs, and
      postoperatively at 2 weeks and 3 and 6 months. The Insall-Salvati, Blackburne
      Peel, and Caton-Deschamps indices and a modified Miura and Kawamura index were
      used to calculate patellar height. Posterior tibial slope was also calculated for
      preoperative and 6-month postoperative knees. RESULTS: Coronal plane alignment
      changed significantly, from 24.6% to 55.2% of the tibial weightbearing axis. The
      overall decrease in patellar height for all patients was significant from
      preoperative assessment to the 2-week postoperative assessment and to both 3
      month and 6-month follow-up with all 4 methods. The Insall-Salvati index
      decreased from 1.03 preoperatively to 0.99 at 2 weeks postoperatively, 0.97 at 3
      months, and 0.95 at 6 months postoperatively. The Blackburne-Peel index decreased
      from 0.90 preoperatively to 0.75, 0.77, and 0.76, respectively, at each
      postoperative interval. The Caton-Deschamps index decreased from 0.98
      preoperatively to 0.87, 0.86, and 0.84 at each postoperative measurement. The
      Miura-Kawamura index changed from 0.76 preoperatively to 0.61, 0.63, and 0.60 for
      each postoperative assessment. The average tibial slope significantly increased
      from 9.0 degrees to 11.9 degrees overall for all patients. In comparing the plate
      position, the tibial slope significantly increased from 8.8 degrees
      preoperatively to 13.1 degrees at 6 months postoperatively for anteromedially
      positioned plates and from 9.3 degrees to 10.3 degrees for posteromedially
      positioned plates. CONCLUSION: Opening-wedge proximal tibial osteotomies decrease
      patellar height within the first 3 postoperative months. Shortening of the
      patellar tendon may affect future surgeries and needs to be evaluated in
      preoperative assessment. Moreover, a significant increase in tibial slope
      occurred, which may affect patellar height and future ligament reconstructions.

PMID- 19767537
TI  - Resistance artery adaptation to pregnancy counteracts the vasoconstricting
      influence of plasma from normal pregnant women.
AB  - Using a rat model, we investigated the effects of circulating factors in
      pregnancy on cerebrovascular and systemic vascular function by comparing myogenic
      reactivity, tone, and endothelial vasodilator production of the posterior
      cerebral artery (PCA) and mesenteric artery (MA) of nonpregnant (NP) animals
      perfused with nonpregnant and pregnant human plasma. Arteries from late pregnant
      (LP) animals were then perfused similarly to evaluate a potential adaptive effect
      of pregnancy on vessel function. A 3-hour exposure to pregnant plasma caused
      increased myogenic reactivity and tone in vessels from NP animals and produced a
      decreased endothelium-derived hyperpolarizing factor response in NP PCAs,
      findings that were not seen with MAs. The increased reactivity and tone noted in
      NP vessels was abolished when pregnant plasma was perfused through LP arteries,
      suggesting these vessels adapt during pregnancy to the vasoconstricting influence
      of pregnant plasma.

PMID- 19767538
TI  - Loss of proliferative capacity in a retroviral immortalized human uterine smooth
      muscle cell line derived from leiomyoma is restored by hTERT overexpression.
AB  - Overexpression of human telomerase reverse transcriptase (hTERT) has facilitated
      establishing in vitro model systems for biological research. The plasmid
      containing hTERT gene was stably transfected into ULTR cells, a retroviral
      transformed human uterine leiomyomatous smooth-muscle cell line. Cells that
      express hTERT, termed as ULTR-hT, shared the morphological characteristics of the
      parental proliferative ULTR cells. They expressed a set of smooth-muscle-specific
      genes and had increased proliferation rate and prolonged lifespan. Quantitative
      real-time polymerase chain reaction (PCR) analysis revealed a correlation of
      proliferation rates of ULTR-hT clonal cells with the level of hTERT expression.
      ULTRhT cells also preserved expression of estrogen, progesterone, and oxytocin
      receptor genes, confirming a myometrial phenotype. Expression of angiotensin II
      receptors and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase
      isoforms were also preserved. Our finding suggests that ULTR-hT cells can be a
      useful in vitro model for studying human myometrium differentiation both in
      pregnancy and pathological growth.

PMID- 19767539
TI  - Do alterations in placental 11beta-hydroxysteroid dehydrogenase (11betaHSD)
      activities explain differences in fetal hypothalamic-pituitary-adrenal (HPA)
      function following periconceptional undernutrition or twinning in sheep?
AB  - Periconceptional undernutrition (UN) in sheep accelerates fetal hypothalamic
      pituitary-adrenal (HPA) axis activation, resulting in preterm birth. In contrast,
      twin conception suppresses fetal HPA function and delays prepartum HPA
      activation. We hypothesized that these dissimilar effects on fetal HPA activity
      result from different influences of maternal glucocorticoid (GC) on maturation of
      the fetal HPA axis, mediated via different activities of placental 11beta
      hydroxysteroid dehydrogenase (11betaHSD) isozymes. We examined the effects of
      twinning and maternal periconceptional UN from 60 days before until 30 days after
      mating on the ontogeny of placental 11betaHSD-1 and -2 enzyme activities. At day
      85 of gestation, placental 11betaHSD-2 activity was lower in UN than in normally
      nourished (N) fetuses (P < .05) and was higher in twins than in singletons (P <
      .05). Furthermore, placental 11betaHSD-1 activity was not different between
      nutritional groups but was higher in twins than in singletons (P = .01). At day
      85, fetal plasma cortisol (P < .001) and cortisone (P < .001) concentrations were
      lower in UN than in N fetuses, but the cortisol to cortisone ratio was higher in
      UN than in N fetuses (P = .01). There was no effect of fetus number on plasma
      cortisol or cortisone concentrations or on the ratio of cortisol to cortisone at
      day 85. Therefore, periconceptional UN and twinning may result in the alterations
      of placental 11betaHSD isozyme activities at particular times during gestation.
      Changes in these activities during critical periods of fetal development could
      affect transplacental transfer or placental generation of GCs that reach the
      fetus, potentially influencing the timing of activation of the fetal HPA axis,
      fetal maturation, and hence the development and health later in life.

PMID- 19767540
TI  - Enhanced expression of P2X4 and P2X7 purinergic receptors in the myometrium of
      pregnant rats in preterm delivery models.
AB  - The expression levels of P2X purinergic receptors were determined in the
      myometrium of pregnant rats using the quantitative real-time reverse
      transcriptase polymerase chain reaction (RT-PCR). The messenger RNAs (mRNAs) of
      P2X4 and P2X7 were expressed most strongly. The expression levels of these
      receptors increased during the late stages of pregnancy; at the time of delivery,
      the mRNA levels of P2X4 and P2X7 had increased to 1.9 and 3.2 times the day 19
      values, respectively. We also explored the roles of P2X receptors in hormone
      induced and inflammation-induced preterm delivery models. In the former,
      mifepristone caused the P2X4 and P2X7 mRNA levels to increase to 2.1 and 4.1
      times the control values, respectively. In the latter, lipopolysaccharide (LPS)
      caused the mRNA levels of P2X4 and P2X7 to increase dramatically to 7.4 and 18.6
      times the control values, respectively. These findings suggest that increased
      P2X4 and P2X7 receptor expression in pregnant rats is related to uterine
      contraction leading to term and preterm delivery.

PMID- 19767541
TI  - The effect of oxytocin and an oxytocin antagonist on the human myometrial
      proteome.
AB  - OBJECTIVE: The immediate effects of oxytocin on myometrial signal transduction
      have been described. However, the longer term effects (up to an hour) on the
      myometrial proteome have not. We combined in vitro contractility with proteomic
      analysis to determine the protein changes associated with oxytocin-induced
      myometrial activity. STUDY DESIGN: Human myometrial biopsies were taken at
      elective caesarean section prior to administration of oxytocics. Strips were
      mounted in an organ bath and exposed to oxytocin (10(-8) mol/L), the oxytocin
      antagonist L372,662 (10(-7) mol/L), or vehicle (n = 5 for each) for 60 minutes.
      Contractility was determined and expressed as a percentage of pretreatment for
      each strip. At the end of the contractility experiment, proteins were extracted
      and separated by two-dimensional (2D) gel electrophoresis. Two-dimensional gels
      were analyzed by PDQuest and proteins of interest identified by mass
      spectrometry. RESULTS: Identified proteins that demonstrated differences as a
      result of treatment with oxytocin or the oxytocin receptor antagonist L372,662
      were Annexin-A3, Osteoglycin, HSP70-protein 2, 2 isoforms of Cytokeratin 19,
      Desmin, EHD2, Protein disulfide isomerase A3, BIGH3, transgelin, thioredoxin
      reductase, triose phosphate isomerase, pyruvate kinase, elongation factor 1gamma,
      and alpha-Actin-3. These proteins can be grouped into 5 classes of protein, those
      associated with cytoskeletal function, contractile/oxidative stress, protein
      synthesis, extracellular matrix proteins, and energy metabolism. CONCLUSION: This
      study demonstrates that oxytocin has longer term (1 hour) effects on the
      myometrial proteome.

PMID- 19767542
TI  - Doppler ultrasonography for the noninvasive measurement of uterine artery volume
      blood flow through gestation in the pregnant sheep.
AB  - Accurate noninvasive quantification of volume blood flow in the uterine arteries
      (UtAs) would have clinical and research benefits. We evaluated the correlation
      and agreement between uterine artery volume blood flow (UtABF) as calculated
      (cUtABF) from color/pulsed-wave Doppler acquisitions and that measured (mUtABF)
      by bilateral perivascular transit-time flow probes in 6 pregnant sheep at 2
      gestational ages. Out of 22 Doppler acquisitions, 19 were successful. The overall
      correlation between cUtABF and mUtABF was 0.55 (n = 19, P = .01). Calculated
      UtABF and mUtABF were significantly correlated in late gestation (n = 11, r =
      0.71, P = .01) but not at mid-gestation (n = 8, r = .02, P = .96). By Bland
      Altman analysis, the mean cUtABF/mUtABF was 1.15 with 95% limit of agreement (
      0.26 to 2.56), similar to results previously achieved using power/pulsed-wave
      Doppler. Despite the acceptable correlation, the limits of agreement between
      Doppler and transit-time flow probe measurements remain wide. This makes Doppler
      ultrasonography less than a desirable method to quantify UtABF in studies where
      accurate quantification is required.

PMID- 19767543
TI  - Menstrual cycle abnormalities among cosmetologists: the Reproductive Outcomes in
      Salon Employees (ROSE) study.
AB  - This study was conducted to examine whether cosmetologists of reproductive age
      are at increased risk of menstrual cycle abnormalities compared to women of the
      same age working in other occupations. Participants in the study (450
      cosmetologists and 511 noncosmetologists) were recruited through mass mailing of
      questionnaires. To be included in the study, respondents to the survey had to be
      between 21 and 55 years of age and not have had a hysterectomy/oophorectomy. The
      main outcome measures included irregular menstrual cycle length and pain during
      menstrual period. The results showed no statistically significant associations
      between being a cosmetologist and having menstrual cycle abnormalities. The
      observed estimates did not differ when including and excluding women who had ever
      used oral contraceptives. Thus, the findings of the study suggest that
      cosmetologists are not at increased risk of menstrual cycle abnormalities.
      Further studies using detailed salon exposure and work task data in relation to
      menstrual cycle outcomes should be conducted.

PMID- 19767544
TI  - Comparison of male and female foot shape.
AB  - BACKGROUND: Morphological and geometric differences between male and female feet
      can be the decisive factor of whether well-fitting, functional, and comfortable
      footwear is available for both men and women. METHODS: Optical scans, plaster
      wrap casts, and a set of manual measurements from the right feet of 51 female
      participants, aged 20 to 59 years (32 +/- 10.2 years), and 39 male participants,
      aged 22 to 71 years (47.1 +/- 12.1 years), were taken to determine which
      parameters were the most significant in characterizing pedal geometry and which
      had the largest difference between male and female feet. RESULTS: Analysis showed
      that the heel-to-ball length (ball length) of the male participants' feet (181.5
      mm) was significantly longer, on average, than that of the female participants'
      feet (165.0 mm). The width of the male paticipants' feet at the ball, instep, and
      heel regions, as well as the ball circumference, normalized by the ball length,
      were all significantly larger on average, than the female test participants'
      feet. However, toe region, instep, and medial and lateral malleoli heights were
      larger, on average, for the female participants than for the male. The results
      show that female feet differ in size and shape from male feet and are not
      algebraically scaled, smaller versions of male feet, as is often assumed.
      CONCLUSIONS: The study shows that the average male participants' feet are longer
      than that of the female participants' feet, while the female feet are relatively
      narrower but higher than those of the male participants.

PMID- 19767545
TI  - An assessment of strapping techniques commonly used for pronated foot
      deformities.
AB  - BACKGROUND: This study investigated the effects of two low-Dye and two high-Dye
      strapping techniques that are commonly used to treat pronatory sequelae. METHODS:
      Plantar pressure distribution in normal adults with a pronated foot type was
      assessed with a commercially available pressure platform system. Twenty study
      participants first walked across the platform barefoot and then with each of the
      four strapping conditions applied. The footprints were averaged and divided into
      seven areas for analysis. RESULTS: Paired t tests found significant differences
      between the barefoot and strapping conditions. Overall, there was a general
      lateralization of pressures indicating an antipronation effect from all strapping
      conditions. Low-Dye strap 2, used to limit the degree of calcaneal eversion,
      produced the most significant changes at the foot pressure areas analyzed.
      CONCLUSIONS: The data reported in this study suggest that the four strapping
      techniques offer different levels of control, and this should be considered
      during the decision-making process and clinical management of pronatory
      conditions. It was the contention of this study that low-Dye strap 2 was the most
      effective strapping technique to control foot mechanics associated with a
      pronated foot type.

PMID- 19767546
TI  - Classification of frontal plane rearfoot motion patterns during the stance phase
      of walking.
AB  - BACKGROUND: Classification of rearfoot motion patterns would assist in
      understanding normal rearfoot motion and would facilitate the identification of
      abnormal motion. We sought to identify common frontal plane rearfoot motion
      patterns in an asymptomatic population. METHODS: Frontal plane rearfoot motion
      was measured with an electromagnetic motion analysis system in 279 asymptomatic
      individuals during barefoot walking. The coefficient of multiple correlation and
      visual observation were used to identify similar patterns of rearfoot motion.
      RESULTS: Four distinct rearfoot motion patterns were identified: pattern 1
      consisted of 176 individuals (63.1%) and was labeled "typical" eversion, pattern
      2 consisted of 87 individuals (31.2%) and was labeled "prolonged eversion,"
      pattern 3 consisted of nine individuals (3.2%) and was labeled "delayed
      eversion," and pattern 4 consisted of seven individuals (2.5%) and was labeled
      "early eversion." CONCLUSIONS: Asymptomatic frontal plane rearfoot motion can be
      classified into four distinct patterns, but most individuals (94.3%) exhibit one
      of two motion patterns (typical or prolonged eversion).

PMID- 19767547
TI  - Quality of life in people with their first diabetic foot ulcer: a prospective
      cohort study.
AB  - BACKGROUND: People with diabetic foot ulcers report poor quality of life.
      However, prospective studies that chart quality of life from the onset of
      diabetic foot ulcers are lacking. We describe change in quality of life in a
      cohort of people with diabetes and their first foot ulcer during 18 months and
      its association with adverse outcomes. METHODS: In this prospective cohort study
      of adults with their first diabetic foot ulcer, the main outcome was change in
      Medical Outcomes Study 36-Item Short Form Health Survey scores between baseline
      and 18-month follow-up. We recorded baseline demographics, diabetes
      characteristics, depression, and diabetic foot outcomes and mortality at 18
      months. RESULTS: In 253 people with diabetes and their first ulcer, there were 40
      deaths (15.8%), 36 amputations (15.5%), 99 recurrences (43.2%), and 52 nonhealing
      ulcers (21.9%). The 36-Item Short Form Health Survey response rate of survivors
      at 18 months was 78% (n = 157). There was a 5- to 6-point deterioration in mental
      component summary scores in people who did not heal (adjusted mean difference, 
      6.54; 95% confidence interval, -12.64 to -0.44) or had recurrent ulcers (adjusted
      mean difference, -5.30; 95% confidence interval, -9.87 to -0.73) and a
      nonsignificant reduction in those amputated (adjusted mean difference, -5.00; 95%
      confidence interval, -11.15 to 1.14). CONCLUSIONS: Quality of life deteriorates
      in people with diabetes whose first foot ulcer recurs or does not heal within 18
      months.

PMID- 19767548
TI  - Effect of 7-degree rearfoot varus and valgus wedging on rearfoot kinematics and
      kinetics during the stance phase of walking.
AB  - BACKGROUND: The scientific evidence behind the mechanical function of foot
      orthoses is still controversial. Research studies that have investigated the
      kinematic effect of foot orthoses on the lower extremity have shown variable
      results, with orthoses causing either no significant change or a small
      significant change in foot kinematics. METHODS: The right limbs of 12 healthy
      asymptomatic individuals were studied in three walking conditions: barefoot, with
      a 7 degrees rearfoot varus wedge, and with a 7 degrees rearfoot valgus wedge.
      Kinematic and kinetic variables measured were the foot progression angle, the
      peak internal tibial rotation angle, and net ankle inversion moments during the
      stance phase in the three conditions. RESULTS: There were statistically
      significant differences in the foot progression angle between the barefoot and
      varus wedge conditions and between the varus and valgus wedge conditions. There
      were no significant changes in peak internal tibial rotation among the three
      conditions tested. However, rearfoot varus wedges significantly reduced net ankle
      inversion moments compared with barefoot and rearfoot valgus wedges. CONCLUSIONS:
      These results support the idea that foot orthoses work by methods other than by
      changing kinematic parameters. The present study supports the concept that foot
      orthoses work primarily by altering kinetics, with their effects on kinematics
      being secondary.

PMID- 19767549
TI  - Biomechanical consequences of total plantar fasciotomy: a review of the
      literature.
AB  - BACKGROUND: Plantar fascia release for chronic plantar fasciitis has provided
      excellent pain relief and rapid return to activities with few reported
      complications. Cadaveric studies have led to the identification of some potential
      postoperative problems, most commonly weakness of the medial longitudinal arch
      and pain in the lateral midfoot. METHODS: An electronic search was conducted of
      the MEDLINE, ScienceDirect, SportDiscus, EMBASE, CINAHL, Cochrane, and AMED
      databases. The keywords used to search these databases were plantar fasciotomy
      and medial longitudinal arch. Articles published between 1976 and 2008 were
      identified. RESULTS: Collectively, results of cadaveric studies suggested that
      plantar fasciotomy leads to loss of integrity of the medial longitudinal arch and
      that total plantar fasciotomy is more detrimental to foot structure than is
      partial fasciotomy. In vivo studies, although limited in number, concluded that
      although clinical outcomes were satisfactory, medial longitudinal arch height
      decreased and the center of pressure of the weightbearing foot was excessively
      medially deviated postoperatively. CONCLUSIONS: Plantar fasciotomy, in particular
      total plantar fasciotomy, may lead to loss of stability of the medial
      longitudinal arch and abnormalities in gait, in particular an excessively
      pronated foot. Further in vivo studies on the long-term biomechanical effects of
      plantar fasciotomy are required.

PMID- 19767550
TI  - Total extrusion of the talus in an adolescent: a case report.
AB  - Talar extrusion in a 13-year-old child was treated by means of open reduction and
      10 weeks of cast immobilization. At 1.5 years of follow-up, the patient had full
      range of motion in the ankle and no signs of avascular necrosis or arthritis.

PMID- 19767551
TI  - Distal tibial epiphyseal fracture (Tillaux) and capsular interposition.
AB  - Arthroscopic-assisted reduction is one recommended technique for pediatric distal
      tibial epiphyseal fractures. A 15-year-old male patient with a triplane distal
      tibial epiphyseal fracture (Tillaux type) was scheduled for arthroscopic
      reduction and pinning, which failed to provide adequate fracture reduction. Open
      surgery was subsequently performed, which revealed a capsular interposition in
      the fracture line attributable to an anterior capsular tear of the ankle. The
      possibility of capsular interposition should always be taken into consideration
      when problems such as those described in this case presentation are encountered
      in such patients. This is precisely why direct visualization either through
      arthroscopy or open arthrotomy is sometimes necessary.

PMID- 19767552
TI  - Unrecognized anterior compartment syndrome following ankle fracture surgery: a
      case report.
AB  - A 35-year-old male sustained a lateral malleolar fracture while playing football.
      The fracture was treated by open reduction and internal fixation with a
      tourniquet. The next day, the patient returned with pain and swelling of the
      ankle and was admitted again to the hospital with a suspected diagnosis of
      cellulitis. Ten hours later, the patient developed the symptoms of anterior
      compartment syndrome. Emergency open fasciotomy of the anterior compartment was
      performed. The retrospective analysis of the patient's history was suggestive of
      a predisposition to an exercise-induced compartment syndrome. We think that
      exertional increase of the compartmental pressure before the injury and the
      tourniquet used during surgery contributed together to the development of
      compartment syndrome. Physicians should be vigilant in identifying the features
      of compartment syndrome when managing patients injured during a sporting
      activity.

PMID- 19767553
TI  - A two-portal posterior endoscopic approach in the treatment of a complex talus
      fracture: a case report.
AB  - The two-portal hindfoot endoscopy is a relatively new technique that is becoming
      increasingly popular. It gives excellent access to the posterior ankle
      compartment, the subtalar joint, and extra-articular structures. We report a 24
      year-old man with a complex talus fracture involving the posterior part of the
      talar body and posterolateral process. He was treated endoscopically, with a two
      portal posterior approach to the hindfoot. This approach allowed a better
      visualization and treatment of accompanying pathologies. Combined excision of the
      posterolateral process and fixation of the fracture was performed with the two
      portal hindfoot endoscopy, which has not been previously described to our
      knowledge. The two-portal posterior endoscopic approach can be an attractive
      treatment alternative for the posterior part fractures of the talus, which can in
      turn, be a new indication for this technique.

PMID- 19767554
TI  - Subtalar arthroereisis for pediatric flexible pes planovalgus: fifteen years
      experience with the cone-shaped implant.
AB  - Flexible pes planovalgus is a common condition with flattening of the medial
      longitudinal arch accompanied by hindfoot valgus. Severe cases of pes planovalgus
      may need surgery, and a technique that has gained popularity over the past
      decades is subtalar arthroereisis. An endoorthotic implant of various shapes is
      inserted in the sinus tarsus, which limits the excessive eversion of the subtalar
      joint present in flexible pes planovalgus. None of these implants, however, allow
      for easy control of the extent of talocalcaneal and talonavicular correction. The
      primary aim of this study was to describe our technique with the custom-built
      cone-shaped implant. Our secondary aim was to evaluate patient satisfaction,
      clinical and radiologic results, and complications with a minimal follow-up of 5
      years. Between January 1992 and June 2002, 40 patients (80 feet) underwent
      subtalar arthroereisis for flexible pes planovalgus. After temporary sinus tarsi
      tenderness (12 feet), implant dislocation (two feet) was the most common
      complication. Questionnaires from 27 patients (54 feet) were analyzed and 44 feet
      were also clinically and radiographically evaluated. Thirteen patients were lost
      to follow-up. Mean (+/- SD) follow-up was 12.6 years (range, 5.9-16.1). Eighty
      one percent of the patients were satisfied with the result. Clinically, normal
      alignment was present in 14 feet, and mild deformities remained in 26 feet.
      Radiographically, the average foot angle measurements were normal. We conclude
      that subtalar arthroereisis is a simple, minimally invasive operative option with
      satisfactory subjective and clinical results after mid- to long-term follow-up.

PMID- 19767555
TI  - Diabetic foot infections: time to change the prognostic concept.
AB  - Patients with diabetic neuropathy are subject to ulcerations that may be
      complicated by infection and gangrene, with subsequent risk of amputation. It is
      the job of the foot specialist to identify and manage these problems early to
      avoid the unfortunate complication of amputation regardless of the presenting
      condition of the patient's limb. We shed light on the hypothesis that suggests
      that infection and gangrene in a diabetic patient aggravate the degree of
      ischemia (microvascular, macrovascular, or both) already present enough to
      endanger the viability of the surrounding tissues unless urgent drainage with
      decompression and debridement of the necrotic sloughs is performed, with
      consequent reduction of tissue pressure and improvement in circulation to the
      area. We present cases with severe infections leading to gangrene and ischemia,
      which were improved following surgical management with consequent improvement in
      tissue viability. In these cases, we demonstrate that immediate treatment of the
      wound despite the delayed presentation of the patients resulted in limb salvage
      with much less soft-tissue loss than expected before treatment.

PMID- 19767556
TI  - Could nebivolol be an alternative drug for the treatment of diabetic foot ulcers?

PMID- 19767557
TI  - Self-assessment of foot health: requirements, issues, practicalities, and
      challenges.
AB  - If self-referent instruments about people's health are to be useful in clinical
      and research settings, those instruments must be developed according to well
      established processes and principles of measurement. We outline the main
      processes that should occur in the development of self-referent measuring
      instruments in general, with a focus, for illustrative purposes, on those
      intended to assess foot health. Requirements and issues concerning different
      forms of reliability and validity receive the most attention. In particular,
      problems associated with indices of test-retest reliability, inter-item
      homogeneity, and construct validity are identified and discussed. Practicalities
      concerning administration and scoring are also considered. A list of questions is
      provided for prospective users to assess the characteristics and quality of self
      referent instruments.

PMID- 19767558
TI  - Extracorporeal shockwave therapy for interdigital neuroma: a randomized, placebo
      controlled, double-blind trial.

PMID- 19767559
TI  - Extracorporeal shockwave therapy for interdigital neuroma: a randomized, placebo
      controlled, double-blind trial.

PMID- 19767560
TI  - Extracorporeal shockwave therapy for interdigital neuroma: a randomized, placebo
      controlled, double-blind trial.

PMID- 19767562
TI  - Comment on "Proteasome regulation of ULBP1 transcription".

PMID- 19767563
TI  - Comment on "The bacterial fermentation product butyrate influences epithelial
      signaling via reactive oxygen species-mediated changes in cullin-1 neddylation".

PMID- 19767564
TI  - How suppressor cells led to anergy, costimulation, and beyond.

PMID- 19767565
TI  - Pillars article: antigen presentation by chemically modified splenocytes induces
      antigen-specific T cell unresponsiveness in vitro and in vivo. J. Exp. Med. 1987.
      165: 302-319.

PMID- 19767566
TI  - Protumor vs antitumor functions of IL-17.
AB  - Inflammation appears to be a necessity for both metastasis and elimination of
      tumor cells. IL-17, a proinflammatory cytokine produced by Th17 cells,
      contributes to both the processes by playing a dual role in the antitumor
      immunity. On one hand, IL-17 promotes an antitumor cytotoxic T cell response
      leading to tumor regression. On the other hand, by facilitating angiogenesis and
      egress of tumor cells from the primary focus, IL-17 promotes tumor growth. Thus,
      the therapeutic application that uses IL-17 needs to be refined by minimizing its
      protumor functions.

PMID- 19767567
TI  - Cutting edge: contribution of lung-resident T cell proliferation to the overall
      magnitude of the antigen-specific CD8 T cell response in the lungs following
      murine influenza virus infection.
AB  - Following influenza virus infection, CD8 T cells encounter mature, Ag-bearing
      dendritic cells within the draining lymph nodes and undergo activation,
      programmed proliferation, and differentiation to effector cells before migrating
      to the lungs to mediate viral clearance. However, it remains unclear whether CD8
      T cells continue their proliferation after arriving in the lungs. To address this
      question, we developed a novel, in vivo, dual-label system using intranasal CFSE
      and BrdU administration to identify virus-specific CD8 T cells that are actively
      undergoing cell division while in the lungs. With this technique we demonstrate
      that a high frequency of virus-specific CD8 T cells incorporate BrdU while in the
      lungs and that this lung-resident proliferation contributes significantly to the
      magnitude of the Ag-specific CD8 T cell response following influenza virus
      infection.

PMID- 19767568
TI  - Cutting edge: CD4-independent development of functional FoxP3+ regulatory T
      cells.
AB  - The CD4 coreceptor is mandatory for the differentiation and function of
      conventional MHC class II-restricted T cells, but little is known about its
      contribution in regulatory T cells (Tregs). We thus investigated the Treg
      compartment in mice lacking CD4. CD3+CD8-FoxP3+ cells were readily detected in
      the periphery of CD4(-/-) mice, where their percentages were even increased as
      compared with wild-type animals. These cells had a classical CD25+CD152+GITR+
      Treg phenotype, were enriched in memory-type Tregs, and displayed a diversified
      TCR repertoire. Functionally, CD4(-/-) Tregs were equally as suppressive as
      CD4(+/+) Tregs in vitro as well as in vivo. Hence, the CD4 coreceptor is
      dispensable for the generation and function of FoxP3+ Tregs. Furthermore, CD3+CD8
      FoxP3+ Tregs were also found to develop in the absence of both CD4 and MHC-II
      molecules, demonstrating that the generation of Tregs can occur independently of
      MHC-II recognition.

PMID- 19767569
TI  - Cutting edge: HLA-DM functions through a mechanism that does not require specific
      conserved hydrogen bonds in class II MHC-peptide complexes.
AB  - HLA-DM catalyzes peptide dissociation and exchange in class II MHC molecules
      through a mechanism that has been proposed to involve the disruption of specific
      components of the conserved hydrogen bond network in MHC-peptide complexes. HLA
      DR1 molecules with alanine substitutions at each of the six conserved H- bonding
      positions were expressed in cells, and susceptibility to DM catalytic activity
      was evaluated by measuring the release of CLIP. The mutants alphaN62A, alphaN69A,
      alphaR76A, and betaH81A DR1 were fully susceptible to DM-mediated CLIP release,
      and betaN82A resulted in spontaneous release of CLIP. Using recombinant soluble
      DR1 molecules, the amino acid betaN82 was observed to contribute
      disproportionately in stabilizing peptide complexes. Remarkably, the catalytic
      potency of DM with each beta-chain mutant was equal to or greater than that
      observed with wild-type DR1. Our results support the conclusion that no
      individual component of the conserved hydrogen bond network plays an essential
      role in the DM catalytic mechanism.

PMID- 19767570
TI  - Cutting edge: Dab2 is a FOXP3 target gene required for regulatory T cell
      function.
AB  - FOXP3-expressing regulatory T (Treg) cells are vital for maintaining peripheral T
      cell tolerance and homeostasis. The mechanisms by which FOXP3 target genes
      orchestrate context-dependent Treg cell function are largely unknown. In this
      study we show that in mouse peripheral lymphocytes the Drosophila Disabled-2
      (Dab2) homolog, a gene that is involved in enhancing TGFbeta responses, is
      exclusively expressed in FOXP3+ regulatory T cells. Dab2 is a direct target of
      FOXP3, and regulatory T cells lacking DAB2 are functionally impaired in vitro and
      in vivo. However, not all aspects of Treg cell function are perturbed, and DAB2
      appears to be dispensable for Treg cell function in maintaining naive T cell
      homeostasis.

PMID- 19767571
TI  - Unbiased quantitation of Escherichia coli membrane proteome using phase transfer
      surfactants.
AB  - We developed a sample preparation protocol for rapid and unbiased analysis of the
      membrane proteome using an alimentary canal-mimicking system in which proteases
      are activated in the presence of bile salts. In this rapid and unbiased protocol,
      immobilized trypsin is used in the presence of deoxycholate and lauroylsarcosine
      to increase digestion efficiency as well as to increase the solubility of the
      membrane proteins. Using 22.5 microg of Escherichia coli whole cell lysate, we
      quantitatively demonstrated that membrane proteins were extracted and digested at
      the same level as soluble proteins without any solubility-related bias. The
      recovery of membrane proteins was independent of the number of transmembrane
      domains per protein. In the analysis of the membrane-enriched fraction from 22.5
      microg of E. coli cell lysate, the abundance distribution of the membrane
      proteins was in agreement with that of the membrane protein-coding genes when
      this protocol, coupled with strong cation exchange prefractionation prior to nano
      LC-MS/MS analysis, was used. Because this protocol allows unbiased sample
      preparation, protein abundance estimation based on the number of observed
      peptides per protein was applied to both soluble and membrane proteins
      simultaneously, and the copy numbers per cell for 1,453 E. coli proteins,
      including 545 membrane proteins, were successfully obtained. Finally, this
      protocol was applied to quantitative analysis of guanosine tetra- and
      pentaphosphate-dependent signaling in E. coli wild-type and relA knock-out
      strains.

PMID- 19767573
TI  - Eruption of primary dentition--a grave health problem according to Spanish
      doctors of the XVI-XVIII centuries.

PMID- 19767574
TI  - Neural crest lineage segregation: a blueprint for periodontal regeneration.
AB  - During the recent decade, the periodontal attachment apparatus has become one of
      the premier areas of the body for the development of novel tissue-engineering
      strategies. In the present review, we describe a developmental biology approach
      to characterize current concepts in periodontal regeneration and to discuss
      strategies for future applications in periodontal therapies. To decipher the
      developmental make-up of the periodontal region, we have followed the path of the
      migratory neural crest, since it gives rise to periodontal progenitor tissues,
      which in turn are subjected to the influence of diverse craniofacial
      extracellular matrices and peptide growth factors. Based on this developmental
      perspective, we have conducted a systematic analysis of the factors, progenitor
      cells, and matrices used in current periodontal tissue-engineering approaches. We
      propose that the developmental history of a tissue is a highly instructive design
      template for the discovery of novel bioengineering tools and approaches.

PMID- 19767575
TI  - Mesenchymal stem cells derived from dental tissues vs. those from other sources:
      their biology and role in regenerative medicine.
AB  - To date, 5 different human dental stem/progenitor cells have been isolated and
      characterized: dental pulp stem cells (DPSCs), stem cells from exfoliated
      deciduous teeth (SHED), periodontal ligament stem cells (PDLSCs), stem cells from
      apical papilla (SCAP), and dental follicle progenitor cells (DFPCs). These
      postnatal populations have mesenchymal-stem-cell-like (MSC) qualities, including
      the capacity for self-renewal and multilineage differentiation potential. MSCs
      derived from bone marrow (BMMSCs) are capable of giving rise to various lineages
      of cells, such as osteogenic, chondrogenic, adipogenic, myogenic, and neurogenic
      cells. The dental-tissue-derived stem cells are isolated from specialized tissue
      with potent capacities to differentiate into odontogenic cells. However, they
      also have the ability to give rise to other cell lineages similar to, but
      different in potency from, that of BMMSCs. This article will review the isolation
      and characterization of the properties of different dental MSC-like populations
      in comparison with those of other MSCs, such as BMMSCs. Important issues in stem
      cell biology, such as stem cell niche, homing, and immunoregulation, will also be
      discussed.

PMID- 19767576
TI  - Mechanical properties of tannic-acid-treated dentin matrix.
AB  - Dentin collagen is a major component of the hybrid layer, and its stability may
      have a great impact on the properties of adhesive interfaces. We tested the
      hypothesis that the use of tannic acid (TA), a collagen cross-linking agent, may
      affect the mechanical properties and stability of the dentin matrix. The present
      study evaluated the effects of different concentrations of TA on the modulus of
      elasticity and enzymatic degradation of dentin matrix. Hence, the effect of TA
      pre-treatment on resin-dentin bond strength was assessed with the use of two
      bonding systems. Sound human molars were used and prepared according to each
      experimental design. The use of TA affected the properties of demineralized
      dentin by increasing its stiffness. TA treatment inhibited the effect of
      collagenase digestion on dentin matrix, particularly for 10%TA and 20%TA. The TA
      dentin matrix complex resulted in improved bond strength for both adhesive
      systems.

PMID- 19767577
TI  - Osteoblast mechanoresponses on Ti with different surface topographies.
AB  - During implant healing, mechanical force is transmitted to osteogenic cells via
      implant surfaces with various topographies. This study tested a hypothesis that
      osteoblasts respond to mechanical stimulation differently on titanium with
      different surface topographies. Rat bone-marrow-derived osteoblastic cells were
      cultured on titanium disks with machined or acid-etched surfaces. A loading
      session consisted of a 3-minute application of a 10- or 20-mum-amplitude
      vibration. Alkaline phosphatase activity and gene expression increased only when
      the cells were loaded in 3 sessions/day on machined surfaces, regardless of the
      vibration amplitude, whereas they were increased with 1 loading session/day on
      the acid-etched surface. The loading did not affect the osteoblast proliferation
      on either surface, but selectively enhanced the cell spreading on the machined
      surface. Analysis of the data suggests that osteoblastic differentiation is
      promoted by mechanical stimulation on titanium, and that the promotion is
      disproportionate, depending on the titanium surface topography. The frequency of
      mechanical stimulation, rather than its amplitude, seemed to have a key role.

PMID- 19767578
TI  - Surface conditioning influences zirconia ceramic bonding.
AB  - Air-abrasion seems to be mandatory for durable resin bonding to zirconia ceramic.
      Air-abrasion might compromise the ceramic strength by creating surface defects.
      Therefore, omitting air-abrasion or using reduced air-pressure seems desirable.
      We tested the null hypotheses that omitting air-abrasion or using reduced air
      pressure does not affect zirconia ceramic bonding independent of using primers.
      Three mechanical surface conditions (polished, air-abraded at 0.05 or at 0.25
      MPa) and 4 priming conditions were tested. After different surface conditioning,
      zirconia ceramic specimens were bonded, and tensile bond strengths were evaluated
      after water storage for 3 days or for 150 days with additional 37,500 thermal
      cyclings for artificial aging. Omitting air-abrasion resulted in debonding during
      artificial aging independent of using primers. The combination of air-abrasion
      and priming improved long-term resin bonding to zirconia ceramic significantly.
      With low-pressure air-abrasion, surface roughness was reduced without affecting
      long-term bond strength, provided that adequate adhesive primers were applied.

PMID- 19767579
TI  - Mmp-20 and Klk4 cleavage site preferences for amelogenin sequences.
AB  - Mmp-20 and Klk4 are the two key enamel proteases. Can both enzymes process
      amelogenin to generate the major cleavage products that accumulate during the
      secretory stage of amelogenesis? We isolated Mmp-20 and Klk4 from developing pig
      teeth and used them to digest the tyrosine-rich amelogenin polypeptide (TRAP),
      the leucine-rich amelogenin protein (LRAP), and 5 fluorescence peptides. We
      characterized the digestion products by LC-MSMS, SDS-PAGE, and C18 RP-HPLC
      monitored with fluorescence and UV detectors. Mmp-20 cleaves amelogenin sequences
      after Pro(162), Ser(148), His(62), Ala(63), and Trp(45). These cleavages generate
      all of the major cleavage products that accumulate in porcine secretory-stage
      enamel: the 23-kDa, 20-kDa, 13-kDa, 11-kDa, and 6-kDa (TRAP) amelogenins. Mmp-20
      cleaves LRAP after Pro(45) and Pro(40), producing the two LRAP products
      previously identified in tooth extracts. Among these key cleavage sites, Klk4 was
      able to cleave only after His(62). We propose that Mmp-20 alone processes
      amelogenin during the secretory stage.

PMID- 19767580
TI  - Eph/ephrinB mediate dental pulp stem cell mobilization and function.
AB  - Damage to the dentin matrix investigates the proliferation and mobilization of
      dental progenitor cells to the injury site, the mechanisms of which are not
      defined. EphB receptors and ephrin-B ligands expressed within the perivascular
      niche of dental pulp have been implicated following tooth injury. We propose that
      elevated levels of ephrin-B1 following injury may prevent the proliferation and
      migration of dental pulp stem cell (DPSC), while EphB/ephrin-B interaction
      facilitates odontoblastic differentiation. The migration, proliferation, and
      differentiation of DPSC in response to Eph/ephrin-B molecules was assessed in an
      established ex vivo tooth injury model and by in vitro assays for the assessment
      of colony formation and differentiation. Analysis of our data demonstrated that
      EphB forward signaling promoted DPSC proliferation, while inhibiting migration.
      Conversely, reverse signaling enhanced DPSC mineral production. These
      observations suggest that EphB/ephrin-B molecules are important for perivascular
      DPSC migration toward the dentin surfaces and differentiation into functional
      odontoblasts, following damage to the dentin matrix.

PMID- 19767581
TI  - Angiogenic signaling triggered by cariogenic bacteria in pulp cells.
AB  - The inflammation observed in the dental pulp of teeth with deep caries lesions is
      characterized by a significant increase in blood vessel density. It is known that
      lipoteichoic acid (LTA) from Gram-positive cariogenic bacteria induces expression
      of vascular endothelial growth factor (VEGF) in dental pulp cells. The hypothesis
      underlying this study was that LTA induces VEGF expression in dental pulp cells
      through TLR2 and PI3k/Akt signaling. Odontoblast-like cells (MDPC-23) and
      undifferentiated pulp cells (OD-21) were exposed to LTA from Streptococcus
      sanguis, and the role of TLR2, PI3K/Akt, and IKK signaling in LTA-induced VEGF
      expression was evaluated. These studies demonstrated that TLR2 signaling through
      the PI3K-Akt pathway is necessary for LTA-induced VEGF expression in pulp cells.
      In contrast, inhibition of IKK signaling did not prevent VEGF up-regulation in
      response to LTA. Understanding signaling pathways triggered by cariogenic
      bacteria may reveal novel therapeutic targets for the clinical management of
      pulpitis.

PMID- 19767582
TI  - Poisson analysis of streptococcal bond-strengthening on saliva-coated enamel.
AB  - The forces responsible for bond-strengthening in initial oral bacterial adhesion
      are unknown. Since Lifshitz-Van der Waals and electrostatic forces work
      instantaneously upon approach, it is hypothesized that bond-strengthening is
      governed by hydrogen bonding. Poisson analysis of adhesion forces observed during
      the retraction of bacterial probes from surfaces in atomic force microscopy can
      be used to analyze the nature of the adhesion forces. Streptococcal adhesion
      forces increased from about -0.7 to -10.3 nN when the contact time between cell
      surfaces and salivary films on enamel was increased from 0 to 120 sec. Initial
      and final adhesion forces were stronger for initial colonizers of tooth surfaces
      (S. mitis, S. sanguinis) than for later, more cariogenic, strains (S. sobrinus,
      S. mutans). Retraction curves after increased contact times showed minor peaks,
      representative of hydrogen bonds, and Poisson analyses indicated repulsive non
      specific forces of around +0.3 nN and slightly more attractive hydrogen-bonding
      forces (-1.0 nN) for initial than for late colonizers (-0.8 nN).

PMID- 19767583
TI  - Histatins enhance wound closure with oral and non-oral cells.
AB  - The role of human saliva in oral wound-healing has never been fully elucidated.
      We previously demonstrated that parotid-salivary histatins enhance in vitro wound
      closure. The question remains whether other salivary-gland secretions enhance
      wound closure, and also the effects of histatins on primary and non-oral cells.
      Since the presence of histatins is not limited to parotid saliva, we expected to
      observe wound-closure activity of other salivary-gland secretions. However, here
      we show that non-parotid saliva does not stimulate wound closure, most probably
      due to the presence of mucins, since the addition of MUC5B to parotid saliva
      abolished its effect. Furthermore, we found that histatins stimulated wound
      closure of (primary) cells of both oral and non-oral origin. This suggests that
      the cellular receptor of histatins is widely expressed and not confined to cells
      derived from the oral cavity. These findings encourage the future therapeutic
      application of histatins in the treatment of all kinds of wounds.

PMID- 19767584
TI  - Acceleration of purine degradation by periodontal diseases.
AB  - Periodontal diseases, such as gingivitis and periodontitis, are characterized by
      bacterial plaque accumulation around the gingival crevice and the subsequent
      inflammation and destruction of host tissues. To test the hypothesis that
      cellular metabolism is altered as a result of host-bacteria interaction, we
      performed an unbiased metabolomic profiling of gingival crevicular fluid (GCF)
      collected from healthy, gingivitis, and periodontitis sites in humans, by liquid
      and gas chromatography mass spectrometry. The purine degradation pathway, a major
      biochemical source for reactive oxygen species (ROS) production, was
      significantly accelerated at the disease sites. This suggests that periodontal
      disease-induced oxidative stress and inflammation are mediated through this
      pathway. The complex host-bacterial interaction was further highlighted by
      depletion of anti-oxidants, degradation of host cellular components, and
      accumulation of bacterial products in GCF. These findings provide new mechanistic
      insights and a panel of comprehensive biomarkers for periodontal disease
      progression.

PMID- 19767585
TI  - Stability of the JP2 clone of Aggregatibacter actinomycetemcomitans.
AB  - The JP2 clone of Aggregatibacter actinomycetemcomitans is strongly associated
      with aggressive periodontitis. To obtain information about colonization dynamics
      of the JP2 clone, we used PCR to examine its presence in 365 Moroccan juveniles
      from whom periodontal plaque samples were collected at baseline and after one and
      two years. Periodontal attachment loss was measured at baseline and at the two
      year follow-up. At baseline, 43 (12%) carriers of the JP2 clone were found.
      Nearly half (44 %) of these were persistently colonized with the clone. The
      relative risk for the development of aggressive periodontitis, adjusted for the
      concomitant presence of other genotypes of A. actinomycetemcomitans, was highest
      for individuals continuously infected by the JP2 clone (RR = 13.9; 95% CI, 9.0 to
      21.4), indicating a relationship between infectious dose and disease, which
      further substantiates the evidence for the JP2 clone as a causal factor in
      aggressive periodontitis.

PMID- 19767586
TI  - Novel RUNX2 mutations in Chinese individuals with cleidocranial dysplasia.
AB  - Cleidocranial dysplasia (CCD) is an inherited autosomal-dominant skeletal disease
      caused by heterozygous mutations in the osteoblast-specific transcription factor,
      RUNX2. We performed mutation analysis of RUNX2 on four unrelated Chinese
      individuals with CCD. Three novel distinct mutations were detected in the coding
      region of RUNX2: two missense and one frameshift. These mutations were
      exclusively clustered within the Runt domain. One missense mutation converts
      threonine to isoleucine at codon 200 (T200I). The other one substitutes leucine
      for arginine at codon 225 (R225L), which affects many family members. The frame
      shift mutation (214fs) in exon3 leads to the introduction of a translational stop
      codon at codon 221, resulting in a truncated RUNX2 protein. The reporter gene
      assays revealed that all the mutants exhibited significantly reduced
      transactivation activities on the osteocalcin promoter. Our results provide new
      genetic evidence that mutations involved in RUNX2 contribute to CCD.
      ABBREVIATIONS: AML3, gene encoding acute myeloid leukemia protein 3; bp, base
      pair; CBFA1, gene encoding core-binding factor 1; CBFbeta, gene encoding core
      binding factor beta; CCD, cleidocranial dysplasia; NLS, nuclear localization
      signal; OSE2, osteoblast-specific cis-acting element 2; PEBP2A, gene encoding
      polyoma enhancer binding protein 2A; PST, proline/serine/ threonine-rich domain;
      Q/A, glutamine-alanine repeat domain; Runt, Runt Homology Domain; RUNX2, the
      mammalian runt-related genes 2; RUNX2, Runt-related protein 2.

PMID- 19767587
TI  - Development and characterization of reference materials for MTHFR, SERPINA1, RET,
      BRCA1, and BRCA2 genetic testing.
AB  - Well-characterized reference materials (RMs) are integral in maintaining clinical
      laboratory quality assurance for genetic testing. These RMs can be used for
      quality control, monitoring of test performance, test validation, and proficiency
      testing of DNA-based genetic tests. To address the need for such materials, the
      Centers for Disease Control and Prevention established the Genetic Testing
      Reference Material Coordination Program (GeT-RM), which works with the genetics
      community to improve public availability of characterized RMs for genetic
      testing. To date, the GeT-RM program has coordinated the characterization of
      publicly available genomic DNA RMs for a number of disorders, including cystic
      fibrosis, Huntington disease, fragile X, and several genetic conditions with
      relatively high prevalence in the Ashkenazi Jewish population. Genotypic
      information about a number of other cell lines has been collected and is also
      available. The present study includes the development and commutability/genotype
      characterization of 10 DNA samples for clinically relevant mutations or sequence
      variants in the following genes: MTHFR; SERPINA1; RET; BRCA1; and BRCA2. DNA
      samples were analyzed by 19 clinical genetic laboratories using a variety of
      assays and technology platforms. Concordance was 100% for all samples, with no
      differences observed between laboratories using different methods. All DNA
      samples are available from Coriell Cell Repositories and characterization
      information can be found on the GeT-RM website.

PMID- 19767588
TI  - Multiple sequence variants in hereditary hemorrhagic telangiectasia cases:
      illustration of complexity in molecular diagnostic interpretation.
AB  - Hereditary hemorrhagic telangiectasia is an autosomal dominant disease caused by
      mutations in the ACVRL1 and ENG genes characterized by arterio-venous
      malformations and telangiectases. Over 700 mutations have been described in these
      two genes, and missense mutations are common. We describe 10 cases in which more
      than one potentially pathogenic mutation was identified. We report that 8 novel
      missense mutations, as well as previously reported pathogenic missense mutations,
      were seen in combination with a second mutation, which raises questions with
      regards to their respective pathogenicity. Our data and discussion indicate the
      challenges of classifying missense mutations as pathogenic or benign and the
      value of co-segregation studies, as well as suggest that there may be hereditary
      hemorrhagic telangiectasia gene mutations that have only mild phenotypic effects.
      We present evidence to suggest that four missense mutations (ENG p.G331S, ENG
      p.L8P, ENG p.P452L and ACVRL1 p.C344R) are pathogenic, two novel mutations
      (ACVRL1 p.A311T and ENG p.S576G) are neutral, and two previously reported disease
      causing mutations are benign or have suspected benign variants (ACVRL1 p.A482V
      and ENG p.V504M). We conclude that for the purpose of establishing a causative
      hereditary hemorrhagic telangiectasia mutation in a family proband, all exons and
      intron/exon borders of both genes should be sequenced and deletion/duplication
      analysis should be performed unless a mutation that is well-proven to be
      pathogenic is identified.

PMID- 19767589
TI  - Detection and characterization of NF1 microdeletions by custom high resolution
      array CGH.
AB  - In 5% to 10% of cases, neurofibromatosis type 1 is caused by microdeletions
      scattered across the entire NF1 gene and various neighboring genes. The phenotype
      appears to be more severe in patients with NF1 microdeletions than in patients
      with NF1 single point mutations. We have developed a new method for detecting and
      characterizing NF1 microdeletions based on a custom high-resolution
      oligonucleotide array comparative genomic hybridization by using the custom 8x15K
      Agilent array format. The array comprised a total of 14,207 oligonucleotide
      probes spanning the whole of chromosome 17, including 12,314 probes spanning an
      approximately 8 Mb interval surrounding the NF1 locus. We validated this approach
      by testing NF1 microdeleted DNA samples previously characterized by means of
      microsatellites and real-time PCR methods. Our array comparative genomic
      hybridization provided enough information for subsequent long-range PCR and
      nucleotide sequencing of the microdeletion endpoints. Unlike previously described
      methods, our array comparative genomic hybridization was able to unambiguously
      differentiate between the three types of microdeletions (type I, type II, and
      atypical) and to characterize atypical microdeletions. Further comparative
      studies of patients with well-characterized genotypes and phenotypes and
      different microdeletions sizes and breakpoints will help determine whether
      haploinsufficiency of deleted genes and/or genes rearrangements influence
      clinical outcomes.

PMID- 19767590
TI  - Effects of ozone exposure during microarray posthybridization washes and
      scanning.
AB  - The increasing prevalence of array-based comparative genomic hybridization in the
      clinical laboratory necessitates the implementation of quality control measures
      to attain accurate results with a high level of confidence. Environmental ozone
      is present in all industrialized cities and has been found to be detrimental to
      array data even at levels considered acceptable by US Environmental Protection
      Agency standards. In this study, we characterized the effect of ozone on
      microarray data on three different labeling platforms that use different
      fluorescent dyes (Cy3 and Cy5, Alexa Fluor 555 and Alexa Fluor 647, and Alexa
      Fluor 3 and Alexa Fluor 5) that are commonly used in array-based comparative
      genomic hybridization. We investigated the effects of ozone on microarray data by
      washing the array in variable ozone environments. In addition, we observed the
      effects of prolonged exposure to ozone on the microarray after washing in an
      ozone-free environment. Our results demonstrate the necessity of minimizing ozone
      exposure when washing and drying the microarray. We also found that washed
      microarrays produce the best results when immediately scanned; however, if a low
      ozone environment is maintained, there will be little compromise in the data
      collected.

PMID- 19767592
TI  - Is the inattentive subtype of ADHD different from the combined/hyperactive
      subtype?
AB  - OBJECTIVE: To compare the ADHD combined/hyperactive subtype (ADHD/CH) to the ADHD
      inattentive subtype (ADHD/I) on the level of comorbidity, treatment response, and
      possible etiological factors. METHOD: A total of 371 clinically referred children
      diagnosed with ADHD aged between 6 and 12 years are recruited for a double-blind,
      placebo-controlled trial of methylphenidate. Comorbidity, treatment response, and
      stress during pregnancy are assessed for each participant. Genotyping is done for
      the DAT, DRD4, and 5-HTT genes. Mothers report smoking or alcohol consumption
      during their pregnancy and their child's birth weight. RESULTS: The ADHD/CH
      children show both a higher frequency of conduct disorder and good response to
      treatment, are exposed to more moderate stress during their mothers' pregnancy,
      and show a higher frequency of L/L genotype for the 5-HTT-linked polymorphic
      region. CONCLUSION: The significant differences found between the ADHD/CH and the
      ADHD/I subtypes raise the possibility that the two may be separate disorders.

PMID- 19767593
TI  - Short-term effectiveness of medication and psychosocial intervention in a cohort
      of newly diagnosed patients with inattention, impulsivity, and hyperactivity
      problems.
AB  - OBJECTIVE: The article discusses the ADHD Observational Research in Europe
      (ADORE) study that examined the impact of early treatment choices on outcome
      within the first few months, in previously untreated children with impairing
      inattention, impulsivity, and hyperactivity. METHODS: Data are collected from a
      longitudinal, observational study conducted in 10 European countries that involve
      1,478 children (aged 6 to 18 years) with symptoms of hyperactivity, impulsivity,
      or inattentiveness. Linear model with a propensity score adjustment compares the
      decrease in ADHD-RS scores between baseline and last recorded visit across
      treatment groups (2 to 5 months). RESULTS: At baseline, 49.9% of participants are
      prescribed pharmacotherapy and 44.3% a psychosocial intervention. Analysis of the
      effect of treatment on the evolution of ADHD-RS scores shows a positive effect of
      medications and either an insignificant or negative effect of psychosocial
      intervention. CONCLUSIONS: Early use of medication effectively reduces ADHD
      symptoms in routine clinical practice in Europe. The effect of psychosocial
      intervention has to be interpreted cautiously because the number, length, and
      level of standard of the sessions are not taken into account in the analyses.

PMID- 19767591
TI  - Contribution of transcranial magnetic stimulation to the understanding of
      functional recovery mechanisms after stroke.
AB  - Motor impairments are a major cause of morbidity and disability after stroke.
      This article reviews evidence obtained using transcranial magnetic stimulation
      (TMS) that provides new insight into mechanisms of impaired motor control and
      disability. They briefly discuss the use of TMS in the diagnosis, prognosis, and
      therapy of poststroke motor disability. Particular emphasis is placed on TMS as a
      tool to explore mechanisms of neuroplasticity during spontaneous and treatment
      induced recovery of motor function to develop more rational and clinically useful
      interventions for stroke rehabilitation.

PMID- 19767594
TI  - Parent perceived impact of Spaniard boys' and girls' inattention, hyperactivity,
      and oppositional defiant behaviors on family life.
AB  - OBJECTIVE: This study examined the impact of inattention, hyperactivity, and
      oppositional defiant disorder (ODD) behaviors and gender on family life. METHOD:
      We created scales for the Family Experiences Inventory (FEI) in a nonclinical
      sample of Spaniard families with children ages 6 to 12 years (N = 369) and
      analyzed the perceived impact of these three behavior dimensions on family
      experiences. RESULTS: Multiple regression analyses indicated that ODD behaviors
      were uniquely correlated with Total FEI and its dimensions. Inattention was also
      uniquely related to higher negative Impact on School Relations and lower Positive
      Impact on Parents scales. Finally, gender-hyperactivity interactions indicated
      that boys with higher hyperactivity scores were more likely to score higher on
      the FEI Total, School Relations, and Siblings scales, and more likely to score
      lower on the Positive Impact on Parents scale than girls. CONCLUSIONS: These
      findings suggested that parents perceive greater child-related impact and place
      greater burden from having a male child with hyperactivity. Inattention,
      hyperactivity, and oppositional defiant behaviors are associated with global
      parent-child interactive stress but the pattern of associations will vary
      depending upon the behavior, child gender, and context of family life examined.

PMID- 19767595
TI  - Hyperactive-impulsive symptoms associated with self-reported sleep quality in
      nonmedicated adults with ADHD.
AB  - OBJECTIVE: Individuals with ADHD often report sleep problems. Though most studies
      on ADHD and sleep examined children or nonclinically diagnosed adults, the
      present study specifically examines nonmedicated adults with ADHD to determine
      whether inattentive and hyperactive-impulsive symptoms are associated with sleep
      problems. METHOD: A total of 22 nonmedicated adults diagnosed with ADHD are
      assessed with a DSM-IV-based interview and the Pittsburg Sleep Quality Index
      (PSQI). RESULTS: The number of hyperactive-impulsive symptoms indicate a positive
      correlation with sleep duration, habitual sleep efficiency, and global PSQI
      score. No significant associations are found between inattentive symptoms and
      sleep quality. CONCLUSION: The results show that sleep problems are associated
      with hyperactive and impulsive symptoms in nonmedicated adults with ADHD. These
      findings provide information on the nature of sleep problems without the
      confounding effects of medication associated with ADHD. Treatment of sleep
      problems, especially in those with hyperactive-impulsive symptoms, may help
      ameliorate ADHD symptomatology.

PMID- 19767596
TI  - Nonmedical prescription stimulant use among a sample of college students:
      relationship with psychological variables.
AB  - OBJECTIVE: To further investigate use and potential misuse of prescription
      stimulants (e.g., Ritalin, Adderall, Concerta) among a sample of college students
      and to explore the relationship between psychological variables and nonmedical
      stimulant use. METHOD: The sample consisted of 390 college students (71.6%
      female, 28.4% male). Participants were asked to complete five questionnaires
      concerning demographic information, prescription stimulant use, internal
      restlessness, sensation seeking, and psychological distress. RESULTS: The study
      findings revealed that, regarding nonprescribed stimulants, 7.5% reported use
      within the past 30 days; 60% reported knowing students who misused stimulants;
      and 50% agreed or strongly agreed that prescription stimulants were "easy to get
      on this campus." Findings further revealed a relationship between stimulant use
      and degree of psychological distress and internal restlessness. CONCLUSIONS:
      Continued research regarding psychological variables, specific group membership
      (e.g., fraternity, sorority, athletics), and stimulant acquisition is suggested.
      Effective prevention and education efforts are needed to help address the
      nonmedical use of prescription stimulants on college campuses.

PMID- 19767597
TI  - Resilience and well-being in college students with and without a diagnosis of
      ADHD.
AB  - OBJECTIVE: The study examines psychological well-being and self-concept in
      college students diagnosed with ADHD. METHOD: We surveyed 17 undergraduate
      college students with ADHD and 19 undergraduate controls concerning academic and
      emotional support received from family and friends. All students completed the
      Connor's Continuous Performance Test (CPT-II), Connor's Adult Rating Scale
      (CAARS), Tennessee Self-Concept Scale (TSCS:2) and Psychological Well-Being Scale
      (PWB). RESULTS: Between group differences were significant for the CAARS and CPT
      II, but not total self-concept (TSC) or global PWB. The strongest predictors for
      TSC were environmental mastery (PWB) for the ADHD group and positive relations
      with others (PWB) for the controls. Students with ADHD reported significantly
      higher paternal support than controls who reported significantly greater support
      from friends. CONCLUSION: College students with a diagnosis of ADHD may represent
      an especially resilient group. Future studies should investigate competencies of
      students with ADHD who have achieved success against the odds.

PMID- 19767598
TI  - Development of a novel output value for quantitative assessment in methylated DNA
      immunoprecipitation-CpG island microarray analysis.
AB  - In DNA methylation microarray analysis, quantitative assessment of intermediate
      methylation levels in samples with various global methylation levels is still
      difficult. Here, specifically for methylated DNA immunoprecipitation-CpG island
      (CGI) microarray analysis, we developed a new output value. The signal log ratio
      reflected the global methylation levels, but had only moderate linear correlation
      (r = 0.72) with the fraction of DNA molecules immunoprecipitated. By multiplying
      the signal log ratio using a coefficient obtained from the probability value that
      took account of signals in neighbouring probes, its linearity was markedly
      improved (r = 0.94). The new output value, Me value, reflected the global
      methylation level, had a strong correlation also with the fraction of methylated
      CpG sites obtained by bisulphite sequencing (r = 0.88), and had an accuracy of
      71.8 and 83.8% in detecting completely methylated and unmethylated CGIs. Analysis
      of gastric cancer cell lines using the Me value showed that methylation of CGIs
      in promoters and gene bodies was associated with low and high, respectively, gene
      expression. The degree of demethylation of promoter CGIs after 5-aza-2'
      deoxycytidine treatment had no association with that of induction of gene
      expression. The Me value was considered to be useful for analysis of intermediate
      methylation levels of CGIs.

PMID- 19767599
TI  - Nucleotide sequence analysis of the enterotoxigenic Escherichia coli Ent plasmid.
AB  - We report here the complete nucleotide sequence of pEntH10407 (65 147 bp), an
      enterotoxigenic Escherichia coli enterotoxin plasmid (Ent plasmid), which is self
      transmissible at low frequency. Within the plasmid, we identified 100 open
      reading frames (ORFs) which could encode polypeptides. These ORFs included
      regions encoding heat-labile (LT) and heat-stable (STIa) enterotoxins, regions
      encoding tools for plasmid replication and an incomplete tra (conjugation)
      region. The LT and STIa region was located 13.5 kb apart and was surrounded by
      three IS1s and an IS600 in opposite reading orientations, indicating that the
      enterotoxin genes may have been horizontally transferred into the plasmid. We
      identified a single RepFIIA replication region (2.0 kb) including RepA proteins
      similar to RepA1, RepA2, RepA3 and RepA4. The incomplete tra region was made up
      of 17 tra genes, which were nearly identical to the corresponding genes of R100,
      and showed evidence of multiple insertions of ISEc8 and ISEc8-like elements.
      These data suggest that pEntH10407 has the mosaic nature characteristic of
      bacterial virulence plasmids, which contains information about its evolution.
      Although the tra genes might originally have rendered pEntH10407 self
      transferable to the same degree as R100, multiple insertion events have occurred
      in the tra region of pEntH10407 to make it less mobile. Another self
      transmissible plasmid might help pEntH10407 to transfer efficiently into H10407
      strain. In this paper, we suggest another possibility: that the enterotoxigenic
      H10407 strain might be formed by auto-transfer of pEntH10407 at a low rate using
      the incomplete tra region.

PMID- 19767600
TI  - Rank of correlation coefficient as a comparable measure for biological
      significance of gene coexpression.
AB  - Information regarding gene coexpression is useful to predict gene function.
      Several databases have been constructed for gene coexpression in model organisms
      based on a large amount of publicly available gene expression data measured by
      GeneChip platforms. In these databases, Pearson's correlation coefficients (PCCs)
      of gene expression patterns are widely used as a measure of gene coexpression.
      Although the coexpression measure or GeneChip summarization method affects the
      performance of the gene coexpression database, previous studies for these
      calculation procedures were tested with only a small number of samples and a
      particular species. To evaluate the effectiveness of coexpression measures,
      assessments with large-scale microarray data are required. We first examined
      characteristics of PCC and found that the optimal PCC threshold to retrieve
      functionally related genes was affected by the method of gene expression database
      construction and the target gene function. In addition, we found that this
      problem could be overcome when we used correlation ranks instead of correlation
      values. This observation was evaluated by large-scale gene expression data for
      four species: Arabidopsis, human, mouse and rat.

PMID- 19767601
TI  - Public exposure to hazards associated with natural radioactivity in open-pit
      mining in Ghana.
AB  - The results of studies carried out on public exposure contribution from naturally
      occurring radioactive materials (NORMS) in two open-pit mines in the Western and
      Ashanti regions of Ghana are reported. The studies were carried out under
      International Atomic Energy Agency-supported Technical Co-operation Project
      GHA/9/005. Measurements were made on samples of water, soil, ore, mine tailings
      and air using gamma spectrometry. Solid-state nuclear track detectors were used
      for radon concentration measurements. Survey was also carried out to determine
      the ambient gamma dose rate in the vicinity of the mines and surrounding areas.
      The effective doses due to external gamma irradiation, ingestion of water and
      inhalation of radon and ore dusts were calculated for the two mines. The average
      annual effective dose was found to be 0.30 +/- 0.06 mSv. The result was found to
      be within the levels published by other countries. The study provides a useful
      information and data for establishing a comprehensive framework to investigate
      other mines and develop guidelines for monitoring and control of NORMS in the
      mining industry and the environment as a whole in Ghana.

PMID- 19767602
TI  - A study of background radioactivity level for Tekirdag, Turkey.
AB  - The level of background radiation for Tekirdag province of north-western Turkey
      was assessed in this study. Radon concentrations in indoor air were determined
      using CR-39 nuclear track detectors and the average (222)Rn activity was found to
      be 86 Bq m(-3) (equivalent to an annual effective dose of 2.2 mSv). Measurements
      of gamma doses in air were performed using plastic scintillators and the average
      absorbed gamma dose rates for indoor and outdoor were found to be 5.7 and 5
      microR h(-1), respectively, corresponding to an annual effective dose of 300
      microSv. The radionuclide activity concentrations in soil samples collected from
      the study area were measured through gamma-ray spectrometry and the average
      activities were determined as 29, 39 and 580 Bq kg(-1) for the natural
      radionuclides (238)U, (232)Th and (40)K, respectively, and 5.2 Bq kg(-1) for the
      fission product (137)Cs. The natural radioactivity sources resulted in an annual
      effective dose of 75 microSv. The radioactivity levels of drinking water samples
      were measured as 0.044 and 0.1 Bq l(-1) for gross alpha and gross beta activities
      using a low-background counting technique (equivalent to an annual effective dose
      of 9 microSv). The results of this study showed that the region's background
      radioactivity level is in agreement with most Turkish cities.

PMID- 19767603
TI  - Lung dosimetry for inhaled radon progeny in smokers.
AB  - Cigarette smoking may change the morphological and physiological parameters of
      the lung. Thus the primary objective of the present study was to investigate to
      what extent these smoke-induced changes can modify deposition, clearance and
      resulting doses of inhaled radon progeny relative to healthy non-smokers (NSs).
      Doses to sensitive bronchial target cells were computed for four categories of
      smokers: (1) Light, short-term (LST) smokers, (2) light, long-term (LLT) smokers,
      (3) heavy, short-term (HST) smokers and (4) heavy, long-term (HLT) smokers.
      Because of only small changes of morphological and physiological parameters,
      doses for the LST smokers hardly differed from those for NSs. For LLT and HST
      smokers, even a protective effect could be observed, caused by a thicker mucus
      layer and increased mucus velocities. Only in the case of HLT smokers were doses
      higher by about a factor of 2 than those for NSs, caused primarily by impaired
      mucociliary clearance, higher breathing frequency, reduced lung volume and airway
      obstructions. These higher doses suggest that the contribution of inhaled radon
      progeny to the risk of lung cancer in smokers may be higher than currently
      assumed on the basis of NS doses.

PMID- 19767604
TI  - Specific absorbed fractions for internal electron emitters derived for a set of
      anatomically realistic reference pregnant female models.
AB  - The specific absorbed fraction (Phi), defined by the Medical Internal Radiation
      Dose Committee, is generally applied to evaluate the average absorbed dose in a
      target organ as a result of radioactive materials deposited in a source organ.
      This paper reports a new set of Phi values for internal electron emitters ranging
      from 10 keV to 4 MeV from various internal organs of the mother to the fetus
      based on three newly developed pregnant female tomographic models, called RPI-P3,
      RPI-P6 and RPI-P9. The results show a linear log relationship between Phi values
      and electron energy. The linear log coefficients have been derived and reported.
      The relationship between Phi values and mean distances between source organs and
      the fetus were also determined to allow for individual dosimetry. Since the RPI-P
      models have finer details of human anatomy and more realistic organ volumes and
      geometries, which follow the latest ICRP reference values, the newly derived Phi
      values could be used as reference values in determination of the dose to the
      fetus from internal electron emitters.

PMID- 19767605
TI  - Stem growth habit affects leaf morphology and gas exchange traits in soybean.
AB  - BACKGROUNDS AND AIMS: The stem growth habit, determinate or indeterminate, of
      soybean, Glycine max, varieties affects various plant morphological and
      developmental traits. The objective of this study is to identify the effect of
      stem growth habit in soybean on the stomatal conductance of single leaves in
      relation to their leaf morphology in order to better understand the ecological
      and agronomic significance of this plant trait. METHODS: The stomatal conductance
      of leaves on the main stem was measured periodically under favourable field
      conditions to evaluate g(max), defined as the maximum stomatal conductance at
      full leaf expansion, for four varieties of soybean and their respective
      determinate or indeterminate near isogenic lines (NILs). Leaf morphological
      traits including stomatal density, guard cell length and vein density were also
      measured. KEY RESULTS: The value of g(max) ranged from 0.383 to 0.754 mol H(2)O
      m(-2) s(-1) across all the genotypes for both years. For the four pairs of
      varieties, the indeterminate lines exhibited significantly greater g(max),
      stomatal density, numbers of epidermal cells per unit area and total vein length
      per unit area than their respective determinate NILs in both years. The guard
      cell length, leaf mass per area and single leaf size all tended to be greater in
      the determinate types. The variation of g(max) across genotypes and years was
      well explained by the product of stomatal density and guard cell length (r =
      0.86, P < 0.01). CONCLUSIONS: The indeterminate stem growth habit resulted in a
      greater maximum stomatal conductance for soybean than the determinate habit, and
      this was attributed to the differences in leaf structure. This raises the further
      hypothesis that the difference in stem growth habit results in different water
      use characteristics of soybean plants in the field. Stomatal conductance under
      favourable conditions can be modified by leaf morphological traits.

PMID- 19767606
TI  - Relative potencies of bupivacaine, levobupivacaine, and ropivacaine for neonatal
      spinal anaesthesia.
AB  - BACKGROUND: Comparing the relative potency of new local anaesthetics such as
      levobupivacaine and ropivacaine with bupivacaine by the minimum local analgesic
      concentration model has not been described for neonatal spinal anaesthesia. This
      information is important to compare agents and to determine the most effective
      spinal dose. METHODS: We performed a two-stage study to determine the ED50, the
      ED95, and the relative analgesic potency of isobaric spinal bupivacaine,
      levobupivacaine, and ropivacaine in infants. In phase 1, 81 infants were
      randomized in a Dixon-Massey study to describe the minimum local analgesic dose.
      In phase 2, a further 70 patients were randomly allocated to receive spinal
      anaesthesia with doses in the upper dose-response range to define the ED95.
      RESULTS: The ED50 doses for bupivacaine, levobupivacaine, and ropivacaine were
      estimated by isotonic regression to be 0.30 mg kg(-1) [95% confidence interval
      (CI) 0.25-0.43], 0.55 mg kg(-1) (0.50-0.64), and 0.50 mg kg(-1) (0.43-0.64),
      respectively. The ED(95), respectively, of bupivacaine, levobupivacaine, and
      ropivacaine were 0.96 mg kg(-1) (95% CI 0.83-0.98), 1.18 mg kg(-1) (1.05-1.22),
      and 0.99 mg kg(-1) (0.73-1.50). The relative potency ratios at the ED(50) were
      bupivacaine:levobupivacaine 0.55 (95% CI 0.39-0.88), bupivacaine:ropivacaine 0.61
      (0.41-1.00), and levobupivacaine:ropivacaine 1.09 (0.84-1.45). CONCLUSIONS:
      Appropriate doses for infant spinal anaesthesia are 1 mg kg(-1) of isobaric 0.5%
      bupivacaine and ropivacaine and 1.2 mg kg(-1) of isobaric 0.5% levobupivacaine.

PMID- 19767607
TI  - EMAGE mouse embryo spatial gene expression database: 2010 update.
AB  - EMAGE (http://www.emouseatlas.org/emage) is a freely available online database of
      in situ gene expression patterns in the developing mouse embryo. Gene expression
      domains from raw images are extracted and integrated spatially into a set of
      standard 3D virtual mouse embryos at different stages of development, which
      allows data interrogation by spatial methods. An anatomy ontology is also used to
      describe sites of expression, which allows data to be queried using text-based
      methods. Here, we describe recent enhancements to EMAGE including: the release of
      a completely re-designed website, which offers integration of many different
      search functions in HTML web pages, improved user feedback and the ability to
      find similar expression patterns at the click of a button; back-end refactoring
      from an object oriented to relational architecture, allowing associated SQL
      access; and the provision of further access by standard formatted URLs and a Java
      API. We have also increased data coverage by sourcing from a greater selection of
      journals and developed automated methods for spatial data annotation that are
      being applied to spatially incorporate the genome-wide (approximately 19,000
      gene) 'EURExpress' dataset into EMAGE.

PMID- 19767608
TI  - The University of Minnesota Biocatalysis/Biodegradation Database: improving
      public access.
AB  - The University of Minnesota Biocatalysis/Biodegradation Database (UM-BBD,
      http://umbbd.msi.umn.edu/) began in 1995 and now contains information on almost
      1200 compounds, over 800 enzymes, almost 1300 reactions and almost 500
      microorganism entries. Besides these data, it includes a Biochemical Periodic
      Table (UM-BPT) and a rule-based Pathway Prediction System (UM-PPS)
      (http://umbbd.msi.umn.edu/predict/) that predicts plausible pathways for
      microbial degradation of organic compounds. Currently, the UM-PPS contains 260
      biotransformation rules derived from reactions found in the UM-BBD and scientific
      literature. Public access to UM-BBD data is increasing. UM-BBD compound data are
      now contributed to PubChem and ChemSpider, the public chemical databases. A new
      mirror website of the UM-BBD, UM-BPT and UM-PPS is being developed at ETH Zurich
      to improve speed and reliability of online access from anywhere in the world.

PMID- 19767609
TI  - Influence of local sequence context on damaged base conformation in human DNA
      polymerase iota: molecular dynamics studies of nucleotide incorporation opposite
      a benzo[a]pyrene-derived adenine lesion.
AB  - Human DNA polymerase iota is a lesion bypass polymerase of the Y family, capable
      of incorporating nucleotides opposite a variety of lesions in both near error
      free and error-prone bypass. With undamaged templating purines polymerase iota
      normally favors Hoogsteen base pairing. Polymerase iota can incorporate
      nucleotides opposite a benzo[a]pyrene-derived adenine lesion (dA*); while mainly
      error-free, the identity of misincorporated bases is influenced by local sequence
      context. We performed molecular modeling and molecular dynamics simulations to
      elucidate the structural basis for lesion bypass. Our results suggest that
      hydrogen bonds between the benzo[a]pyrenyl moiety and nearby bases limit the
      movement of the templating base to maintain the anti glycosidic bond conformation
      in the binary complex in a 5'-CAGA*TT-3' sequence. This facilitates correct
      incorporation of dT via a Watson-Crick pair. In a 5'-TTTA*GA-3' sequence the
      lesion does not form these hydrogen bonds, permitting dA* to rotate around the
      glycosidic bond to syn and incorporate dT via a Hoogsteen pair. With syn dA*,
      there is also an opportunity for increased misincorporation of dGTP. These
      results expand our understanding of the versatility and flexibility of polymerase
      iota and its lesion bypass functions in humans.

PMID- 19767610
TI  - Evolutionarily conserved proteins MnmE and GidA catalyze the formation of two
      methyluridine derivatives at tRNA wobble positions.
AB  - The wobble uridine of certain bacterial and mitochondrial tRNAs is modified, at
      position 5, through an unknown reaction pathway that utilizes the evolutionarily
      conserved MnmE and GidA proteins. The resulting modification (a methyluridine
      derivative) plays a critical role in decoding NNG/A codons and reading frame
      maintenance during mRNA translation. The lack of this tRNA modification produces
      a pleiotropic phenotype in bacteria and has been associated with mitochondrial
      encephalomyopathies in humans. In this work, we use in vitro and in vivo
      approaches to characterize the enzymatic pathway controlled by the Escherichia
      coli MnmE*GidA complex. Surprisingly, this complex catalyzes two different GTP-
      and FAD-dependent reactions, which produce 5-aminomethyluridine and 5
      carboxymethylamino-methyluridine using ammonium and glycine, respectively, as
      substrates. In both reactions, methylene-tetrahydrofolate is the most probable
      source to form the C5-methylene moiety, whereas NADH is dispensable in vitro
      unless FAD levels are limiting. Our results allow us to reformulate the bacterial
      MnmE*GidA dependent pathway and propose a novel mechanism for the modification
      reactions performed by the MnmE and GidA family proteins.

PMID- 19767611
TI  - Primary sequence and epigenetic determinants of in vivo occupancy of genomic DNA
      by GATA1.
AB  - DNA sequence motifs and epigenetic modifications contribute to specific binding
      by a transcription factor, but the extent to which each feature determines
      occupancy in vivo is poorly understood. We addressed this question in erythroid
      cells by identifying DNA segments occupied by GATA1 and measuring the level of
      trimethylation of histone H3 lysine 27 (H3K27me3) and monomethylation of H3
      lysine 4 (H3K4me1) along a 66 Mb region of mouse chromosome 7. While 91% of the
      GATA1-occupied segments contain the consensus binding-site motif WGATAR, only
      approximately 0.7% of DNA segments with such a motif are occupied. Using a
      discriminative motif enumeration method, we identified additional motifs
      predictive of occupancy given the presence of WGATAR. The specific motif variant
      AGATAA and occurrence of multiple WGATAR motifs are both strong discriminators.
      Combining motifs to pair a WGATAR motif with a binding site motif for GATA1, EKLF
      or SP1 improves discriminative power. Epigenetic modifications are also strong
      determinants, with the factor-bound segments highly enriched for H3K4me1 and
      depleted of H3K27me3. Combining primary sequence and epigenetic determinants
      captures 52% of the GATA1-occupied DNA segments and substantially increases the
      specificity, to one out of seven segments with the required motif combination and
      epigenetic signals being bound.

PMID- 19767612
TI  - Off-target and a portion of target-specific siRNA mediated mRNA degradation is
      Ago2 'Slicer' independent and can be mediated by Ago1.
AB  - It is known that siRNAs are capable of reducing expression of non-target genes
      due to the interaction of the siRNA guide strand with a partially complementary
      site on the 'off-target' mRNA. In the current study, we show that reduction of
      cellular Ago2 levels has no effect on off-target reduction of endogenous genes
      and that off-target degradation of mRNA can occur even in an Ago2 knockout cell
      line. Using antisense mediated reduction of Ago proteins and chemically modified
      cleavage- and binding-deficient siRNAs, we demonstrate that siRNA mediated off
      target reduction is Ago2 cleavage independent, but does require siRNA interaction
      with either Ago1 or Ago2 and the RISC-loading complex. We also show that
      depletion of P-body associated proteins results in a reduction of off-target
      siRNA-mediated degradation of mRNA. Finally, we present data suggesting that a
      significant portion of on-target siRNA activity is also Ago2 cleavage
      independent, however, this activity does not appear to be P-body associated.

PMID- 19767613
TI  - Impact of DNA-binding position variants on yeast gene expression.
AB  - Transcription factors (TFs) regulate gene expression by binding to specific
      binding sites (TFBSs) in gene promoters. TFBS motifs may contain one or more
      variable positions. Although the prevailing assumption is that nucleotide
      variants at such positions are functionally equivalent, there is increasing
      evidence that such variants play a role in regulation of gene expression. In this
      article, we propose a method for studying the relationship between the expression
      of target genes and nucleotide variants in TFBS motifs at a genome-wide scale in
      Saccharomyces cerevisiae, especially the combinatorial effects of variants at two
      positions. Our analysis shows that nucleotide variations in more than one-third
      of variable positions and in 20% of dependent position pairs are highly
      correlated to gene expression. We define such positions as 'functional'. However,
      some positions are only functional as dependent pairs, but not individually. In
      addition, a significant proportion of the functional positions have been well
      conserved across all yeast-related species studied. We also find that some
      positions require the presence of co-occurring TFs, while others maintain their
      functionality in the absence of a co-occurring TF. Our analysis supports the
      importance of nucleotide variants at variable positions of TFBSs in gene
      regulation.

PMID- 19767614
TI  - Demonstration of all-or-none loss of imprinting in mRNA expression in single
      cells.
AB  - Loss of imprinting (LOI) is the reactivation of the silenced allele of an
      imprinted gene, leading to perturbation of monoallelic expression. We tested the
      hypothesis that LOI of PLAGL1, a representative maternally imprinted gene, occurs
      through an all-or-none process leading to a mixture of fully imprinted and
      nonimprinted cells. Herein using a quantitative RT-PCR-based experimental
      approach, we measured LOI at the single cell level in human trophoblasts and
      demonstrated a broad distribution of LOI among cells exhibiting LOI, with the
      mean centered at approximately 100% LOI. There was a significant (P < 0.01)
      increase in expression after 2 days of 5-aza-2'-deoxycytidine (AZA) treatment and
      a significant (P < 0.01) increase in LOI after both 1 and 2 days of AZA
      treatment, while the distribution remained broad and centered at approximately
      100% LOI. We propose a transcriptional pulsing model to show that the broadness
      of the distribution reflects the stochastic nature of expression between the two
      alleles in each cell. The mean of the distribution of LOI in the cells is
      consistent with our hypothesis that LOI occurs by an all-or-none process. All-or
      none LOI could lead to a second distinct cell population that may have a
      selective advantage, leading to variation of LOI in normal tissues, such as the
      placenta, or in neoplastic cells.

PMID- 19767615
TI  - Tertiary network in mammalian mitochondrial tRNAAsp revealed by solution probing
      and phylogeny.
AB  - Primary and secondary structures of mammalian mitochondrial (mt) tRNAs are
      divergent from canonical tRNA structures due to highly skewed nucleotide content
      and large size variability of D- and T-loops. The nonconservation of nucleotides
      involved in the expected network of tertiary interactions calls into question the
      rules governing a functional L-shaped three-dimensional (3D) structure. Here, we
      report the solution structure of human mt-tRNA(Asp) in its native post
      transcriptionally modified form and as an in vitro transcript. Probing performed
      with nuclease S1, ribonuclease V1, dimethylsulfate, diethylpyrocarbonate and
      lead, revealed several secondary structures for the in vitro transcribed mt
      tRNA(Asp) including predominantly the cloverleaf. On the contrary, the native
      tRNA(Asp) folds into a single cloverleaf structure, highlighting the contribution
      of the four newly identified post-transcriptional modifications to correct
      folding. Reactivities of nucleotides and phosphodiester bonds in the native tRNA
      favor existence of a full set of six classical tertiary interactions between the
      D-domain and the variable region, forming the core of the 3D structure.
      Reactivities of D- and T-loop nucleotides support an absence of interactions
      between these domains. According to multiple sequence alignments and search for
      conservation of Leontis-Westhof interactions, the tertiary network core building
      rules apply to all tRNA(Asp) from mammalian mitochondria.

PMID- 19767616
TI  - 3D-footprint: a database for the structural analysis of protein-DNA complexes.
AB  - 3D-footprint is a living database, updated and curated on a weekly basis, which
      provides estimates of binding specificity for all protein-DNA complexes available
      at the Protein Data Bank. The web interface allows the user to: (i) browse DNA
      binding proteins by keyword; (ii) find proteins that recognize a similar DNA
      motif and (iii) BLAST similar DNA-binding proteins, highlighting interface
      residues in the resulting alignments. Each complex in the database is dissected
      to draw interface graphs and footprint logos, and two complementary algorithms
      are employed to characterize binding specificity. Moreover, oligonucleotide
      sequences extracted from literature abstracts are reported in order to show the
      range of variant sites bound by each protein and other related proteins.
      Benchmark experiments, including comparisons with expert-curated databases
      RegulonDB and TRANSFAC, support the quality of structure-based estimates of
      specificity. The relevant content of the database is available for download as
      flat files and it is also possible to use the 3D-footprint pipeline to analyze
      protein coordinates input by the user. 3D-footprint is available at
      http://floresta.eead.csic.es/3dfootprint with demo buttons and a comprehensive
      tutorial that illustrates the main uses of this resource.

PMID- 19767617
TI  - Evidence of the crucial role of the linker domain on the catalytic activity of
      human topoisomerase I by experimental and simulative characterization of the
      Lys681Ala mutant.
AB  - The functional and structural-dynamical properties of the Lys681Ala mutation in
      the human topoisomerase IB linker domain have been investigated by catalytic
      assays and molecular dynamics simulation. The mutant is characterized by a
      comparable cleavage and a strongly reduced religation rate when compared to the
      wild type protein. The mutant also displays perturbed linker dynamics, as shown
      by analysis of the principal components of the motion, and a reduced
      electrostatic interaction with DNA. Inspection of the inter atomic distances in
      proximity of the active site shows that in the mutant the distance between the
      amino group of Lys532 side chain and the 5' OH of the scissile phosphate is
      longer than the wild type enzyme, providing an atomic explanation for the reduced
      religation rate of the mutant. Taken together these results indicate the
      existence of a long range communication between the linker domain and the active
      site region and points out the crucial role of the linker in the modulation of
      the catalytic activity.

PMID- 19767618
TI  - Phylogenetic screening of a bacterial, metagenomic library using homing
      endonuclease restriction and marker insertion.
AB  - Metagenomics provides access to the uncultured majority of the microbial world.
      The approaches employed in this field have, however, had limited success in
      linking functional genes to the taxonomic or phylogenetic origin of the organism
      they belong to. Here we present an efficient strategy to recover environmental
      DNA fragments that contain phylogenetic marker genes from metagenomic libraries.
      Our method involves the cleavage of 23S ribsosmal RNA (rRNA) genes within pooled
      library clones by the homing endonuclease I-CeuI followed by the insertion and
      selection of an antibiotic resistance cassette. This approach was applied to
      screen a library of 6500 fosmid clones derived from the microbial community
      associated with the sponge Cymbastela concentrica. Several fosmid clones were
      recovered after the screen and detailed phylogenetic and taxonomic assignment
      based on the rRNA gene showed that they belong to previously unknown organisms.
      In addition, compositional features of these fosmid clones were used to classify
      and taxonomically assign a dataset of environmental shotgun sequences. Our
      approach represents a valuable tool for the analysis of rapidly increasing,
      environmental DNA sequencing information.

PMID- 19767619
TI  - A SRS2 homolog from Arabidopsis thaliana disrupts recombinogenic DNA
      intermediates and facilitates single strand annealing.
AB  - Genetic and biochemical analyses of SRS2 homologs in fungi indicate a function in
      the processing of homologous recombination (HR) intermediates. To date, no SRS2
      homologs have been described and analyzed in higher eukaryotes. Here, we report
      the first biochemical characterization of an SRS2 homolog from a multicellular
      eukaryote, the plant Arabidopsis thaliana. We studied the basic properties of
      AtSRS2 and were able to show that it is a functional 3'- to 5'-helicase.
      Furthermore, we characterized its biochemical function on recombinogenic
      intermediates and were able to show the unwinding of nicked Holliday junctions
      (HJs) and partial HJs (PX junctions). For the first time, we demonstrated strand
      annealing activity for an SRS2 homolog and characterized its strand pairing
      activity in detail. Our results indicate that AtSRS2 has properties that enable
      it to be involved in different steps during the processing of recombination
      intermediates. On the one hand, it could be involved in the unwinding of an
      elongating invading strand from a donor strand, while on the other hand, it could
      be involved in the annealing of the elongated strand at a later step.

PMID- 19767620
TI  - The Nrf2-Keap1-ARE toxicity pathway as a cellular sensor for skin sensitizers-
      functional relevance and a hypothesis on innate reactions to skin sensitizers.
AB  - With the tight deadlines set both by the public and by the regulatory authorities
      to replace animal tests for toxicological endpoints relevant to the development
      of cosmetic products, a large number of research projects have recently focused
      on cellular endpoints affected by skin sensitizing compounds. The general aim
      stated in these projects was to find "markers" for skin sensitizers, be it at the
      level of the transcriptome or at the protein level. Rather than talking of
      "cellular markers," the new paradigm "Toxicity testing in the 21st century"
      formulated by the National Academy of Sciences in the United States focuses on
      "Toxicity pathways." A specific marker for any given toxicological endpoint can
      only exist, if specific toxicity pathways, comprising specific sensors, are
      linked to this endpoint. In the context of skin sensitization, one has to ask
      whether there is an innate cellular signaling pathway activated by skin
      sensitizers. Here a significant body of evidence, mainly accumulated in the last
      20 months, is reviewed, indicating that indeed the Nrf2-Keap1-ARE regulatory
      pathway is such a toxicity pathway activated by cysteine-reactive skin
      sensitizers. Whereas first indications on the in vivo relevance are available,
      key questions remain open and can now specifically be addressed. A minority of
      sensitizers, more specifically reacting with lysine residues, appears not to
      activate the Nrf2-Keap1-ARE pathway and might trigger yet another unknown
      toxicity pathway.

PMID- 19767621
TI  - Metallothionein-III provides neuronal protection through activation of nuclear
      factor-kappaB via the TrkA/phosphatidylinositol-3 kinase/Akt signaling pathway.
AB  - Metallothionein (MT)-III is associated with resistance to neuronal injury.
      However, the underlying mechanism for its effects is unclear. The present study
      investigated the mechanisms of MT-III protection of neuronal cells from hypoxia
      or DNA damage-induced cell death. MT-III reduced the hydrogen peroxide- or DNA
      damage-induced effects on neuronal cells, including the cell death, the
      activation of caspase-3 and -9, and the release of mitochondrial cytochrome c to
      the cytoplasm in a dose-dependent manner. MT-III also increased the activation of
      Akt, the phosphorylation and degradation of IkappaB, the nuclear
      translocation/accumulation and the transcriptional activity of nuclear factor
      kappaB (NF-kappaB) in neuronal cells in a dose-dependent manner. The MT-III
      induced antiapoptotic effects and increase in NF-kappaB activity were blocked by
      specific inhibitors of TrkA, phosphatidylinositol-3 kinase (PI3K), Akt, or NF
      kappaB, indicating that MT-III provides neuronal protection by activating NF
      kappaB through the TrkA/PI3K/Akt signaling pathway.

PMID- 19767622
TI  - Alcohol binge drinking during pregnancy and cryptorchidism.
AB  - BACKGROUND: Recent studies have suggested gestational weeks 8-14 as a time window
      of particular importance to the intrauterine development of the male genitalia,
      and prenatal exposure to alcohol is under suspicion as a risk factor for
      cryptorchidism. We examined if prenatal exposure to alcohol, and especially binge
      drinking, during the suggested programming window is associated with an increased
      risk of cryptorchidism. METHODS: The authors used data on 41 268 live born
      singleton boys of mothers who were enrolled into the Danish National Birth Cohort
      in 1996-2002. During early childhood, 1598 cases of cryptorchidism were
      identified and 398 of these were orchiopexy verified. Maternal alcohol
      consumption including number and timing of binge drinking episodes was assessed
      in two computer-assisted telephone interviews around gestational weeks 17 and 32.
      Adjusted hazard ratios (HRs) of cryptorchidism were estimated by Cox regression.
      RESULTS: Average weekly alcohol consumption as well as frequency of binge
      drinking at any time during pregnancy was not associated with risk of
      cryptorchidism. Binge drinking in gestational weeks 7-15 was associated with a
      slightly increased risk of cryptorchidism with adjusted HRs between 1.03 and
      1.66. CONCLUSION: Prenatal exposure to alcohol-measured as average intake as well
      as frequency and timing of binge drinking-was not associated with cryptorchidism.
      Our findings, however, do not rule out that binge drinking during the suggested
      male programming window may increase the risk of cryptorchidism.

PMID- 19767623
TI  - Clinical efficacy and cost-effectiveness of outpatient parenteral antibiotic
      therapy (OPAT): a UK perspective.
AB  - OBJECTIVES: Outpatient parenteral antibiotic therapy (OPAT) is an effective
      treatment strategy for a wide variety of infections as long as clinical risk is
      minimized by conforming to practice guidelines. However, its cost-effectiveness
      has not been established in the setting of the UK National Health Service. We
      examined the clinical efficacy and cost-effectiveness of an OPAT service based in
      a large UK teaching hospital, predominantly using the outpatient 'infusion
      centre' and patient/carer administration models of service delivery. PATIENTS AND
      METHODS: Data on clinical activity and outcomes were collected prospectively on
      334 episodes of treatment administered by the Sheffield OPAT service between
      January 2006 and January 2008. Cost-effectiveness was calculated by comparing
      real costs of OPAT with estimated inpatient costs for these patient episodes
      incorporating two additional sensitivity analyses. RESULTS: Of the OPAT episodes,
      87% resulted in cure or improvement on completion of intravenous therapy. The
      readmission rate was 6.3%, and patient satisfaction was high. OPAT cost 41% of
      equivalent inpatient costs for an Infectious Diseases Unit, 47% of equivalent
      inpatient costs using national average costs and 61% of inpatient costs using
      minimum inpatient costs for each diagnosis. CONCLUSIONS: Using this service
      model, OPAT is safe and clinically effective, with low rates of
      complications/readmissions and high levels of patient satisfaction. OPAT is cost
      effective when compared with equivalent inpatient care in the UK healthcare
      setting.

PMID- 19767624
TI  - Sexually dimorphic effects of alcohol exposure during development on the
      processing of social cues.
AB  - AIMS: The study used an animal model of fetal alcohol spectrum disorders (FASD)
      to investigate the impact of alcohol exposure during a period equivalent to all
      three trimesters in humans on social recognition memory. It was hypothesized that
      the effects on specific aspects of social recognition memory would be sexually
      dimorphic. METHODS: This study exposed rats to ethanol during both the prenatal
      and early postnatal periods. Two control groups included a group exposed to the
      administration procedures but not ethanol and a non-treated group. At
      approximately 90 days, all rats were tested repeatedly in a test of social
      recognition memory with a juvenile animal of the same sex. Experimental rats of
      both sexes were allowed to investigate an unknown juvenile for either 2, 3 or 5
      min and then, after a delay of 30, 60, 120 and 180 min, were allowed to
      investigate the same juvenile for 5 min. RESULTS: Male rats investigated the
      juvenile for much longer than female rats. Ethanol-exposed male rats showed a
      deficit in recognition memory that was evident with longer delays when the
      initial investigation time was either 2- or 3-min long. In contrast, ethanol
      exposed female rats showed a deficit in recognition memory only when the initial
      investigation period was of 2 min. Measurement of oxytocin receptor binding in
      the amygdala region indicated that ethanol exposure lowered oxytocin receptor
      binding in females but not males. CONCLUSIONS: The results suggest that ethanol
      exposure during development caused a deficit in memory duration but not encoding
      in males and a deficit in encoding but not memory duration in females. The
      deficit in ethanol-exposed females may be related to changes in oxytocin
      receptors in the amygdala.

PMID- 19767626
TI  - Examination of electron stains as a substitute for uranyl acetate for the
      ultrathin sections of bacterial cells.
AB  - Electron staining reagents were examined to find a possible substitute for uranyl
      acetate (UA) in electron microscopy of bacterial ultrathin sections. Four kinds
      of stains, platinum blue (Pt-blue), oolong tea extract (OTE), potassium
      permanganate (KMnO(4)) and phosphotungstic acid (PTA), were examined in
      comparison with UA either with or without post-staining with lead citrate (Pb).
      Electron microscopy was performed on sections from Spurr-embedded cells of a Gram
      positive bacterium, Bacillus cereus NBRC 13597, and a Gram-negative bacterium,
      Escherichia coli NBRC 3301. Both Pt-blue and OTE showed staining similar to each
      other and to that of double staining with UA and Pb in B. cereus, while in E.
      coli the cytoplasmic membrane appeared less dense when compared with UA and Pb.
      KMnO(4) stained excessively to some extent, but showed images of the best
      contrast in the cytoplasmic membrane comparable with UA and Pb among the four
      reagents. PTA could stain the peptidoglycan layer but gave images of low quality
      for both bacteria. This study demonstrated that none of the reagents examined
      showed staining results of the same quality or better than the conventional
      method with UA and Pb. However, stains of Pt-blue, OTE and KMnO(4) could possibly
      be an alternative candidate for the UA according to the structure in question.

PMID- 19767625
TI  - Sex differences in ethanol intake and sensitivity to aversive effects during
      adolescence and adulthood.
AB  - AIMS: The present experiments examined sex differences in ethanol intake and in
      the influence of a social context on aversive properties of ethanol in adolescent
      and adult Sprague-Dawley rats. METHODS: Experiment 1 examined ethanol intake,
      with animals receiving daily 2-h access to ethanol and water for 8 days.
      Experiment 2 assessed the aversive effects of ethanol using a conditioned taste
      aversion (CTA) paradigm, with animals placed either alone or with a same-sex,
      same-age peer during the ethanol intoxication phase of conditioning. RESULTS:
      Ethanol intake varied with both age and sex, although the sex differences
      emerging at each age were opposite in nature. Adolescent males consumed more
      ethanol relative to their body weights than adolescent females and adults of both
      sexes, whereas adult females generally consumed more than adult males. The CTA
      test revealed no sex differences in aversive effects of ethanol in adults,
      whereas adolescent males were less sensitive to the aversive properties of
      ethanol than adolescent females when intoxication occurred in the presence of a
      peer. Ethanol-induced CTA was evident in adults at lower doses than in
      adolescents. CONCLUSIONS: These results suggest that age differences in ethanol
      intake in males and sex differences in intake during adolescence may be
      associated in part with the relative insensitivity of the male adolescents to
      ethanol's aversive properties, especially when intoxication occurred in a social
      context. However, the elevated ethanol intake observed in adult females relative
      to their male counterparts appears to be unrelated to the aversive properties of
      ethanol.

PMID- 19767627
TI  - Quantitativeness of phase measurement by transport of intensity equation.
AB  - Based on the transport of intensity equation (TIE), a phase map can be readily
      retrieved from only three images of a focal series. The retrieval procedure does
      not require an iterative calculation and it is performed very fast with the use
      of the fast Fourier transform. However, it must be noted that sensitivity depends
      on the spatial frequency components and difficulties are encountered when phase
      information is retrieved to be of the same quality for all frequency components.
      Since the retrieved phase is influenced by conditions in which the focal series
      was taken, it is important to select the appropriate conditions and parameters
      used in this process. Optimal conditions to preserve the quantitativeness of
      phase maps measured by the TIE method are discussed theoretically and they are
      demonstrated by measuring phase shifts in silver particles. It was found that the
      high quantitativeness can be obtained by selecting appropriately a defocus
      difference and a high pass filter constant according to the frequency components
      for the objects.

PMID- 19767628
TI  - Modified diet in renal disease method overestimates renal function in selected
      elderly patients.
AB  - BACKGROUND: the Modification of Diet in Renal Disease (MDRD) method of renal
      function estimation has not been extensively assessed in elderly patients. We
      needed to assess which renal function estimate was most suited for drug dose
      estimation in our population. METHOD: we compared MDRD with an optimised version
      of the Cockcroft-Gault (CG(opt)) method in a hospital population, using
      gentamicin clearance as a baseline. RESULTS: MDRD overestimated gentamicin
      clearance by 29% (P < 0.001, n = 68), while CG(opt) underestimated by 10% (P <
      0.01). Overestimation by MDRD increased with increasing age. This was 12%, 26%
      and 69% in age groups <65, 65-80 and >80 years respectively (P < 0.001). CG(opt)
      underestimated renal function by -5%, -16% and -4% respectively (P = NS). Bias
      and precision of renal function estimations for the three age groups were less
      for CG(opt) than for MDRD. Age significantly influenced MDRD overestimation in
      this population (P = 0.037). CONCLUSION: MDRD overestimated renal function as age
      increased. While CG(opt) underestimated renal function, this was of a smaller
      magnitude, consistent across age, and thus better suited for dose calculation,
      especially in the elderly. Larger-scale studies using gold standard markers of
      renal function estimation are urgently needed to determine the accuracy of MDRD
      in elderly hospitalised patients.

PMID- 19767629
TI  - Community-based intervention to optimise falls risk management: a randomised
      controlled trial.
AB  - BACKGROUND: falls are the leading causes of accidental death and fragility
      fractures in older adults. Interventions that assess and reduce falls risk are
      underutilised. OBJECTIVE: to evaluate the impact of a multifaceted community
      based programme aimed at optimising evidence-based management of patients at risk
      for fall-related fractures. DESIGN: this was a randomised trial performed from
      2003 to 2006. SETTING: community-based intervention in Ontario, Canada.
      PARTICIPANTS: eligible patients were community-dwelling, aged > or =55 years and
      identified to be at risk for fall-related fractures. A total of 201 patients were
      allocated to the intervention group or to usual care. INTERVENTION: components of
      the intervention included assessment of falls risk, functional status and home
      environment, and patient education. MEASUREMENTS: primary outcome was the
      implementation of appropriate falls risk assessment at 6 months. Secondary
      outcomes included falls and fractures at 6 and 12 months. RESULTS: the mean age
      of participants was 72 years, and 41% had fallen with injury in the previous
      year. Compared to usual care, the intervention increased the number of referrals
      made to physiotherapy [21% (21/101) vs 6.0% (6/100); relative risk (RR) 3.47, 95%
      confidence interval (CI) 1.46-8.22] and occupational therapy [15% (15/101) vs 0%;
      RR 30.7, 95% CI 1.86 to >500]. At 12 months, the number of falls in the
      intervention group was greater than in the usual care group [23% (23/101) vs 11%
      (11/100); RR 2.07, 95% CI 1.07-4.02]. CONCLUSIONS: compared to usual care, a
      multi-faceted intervention increased referrals to physiotherapy and occupational
      therapy but did not reduce risk of falls. Similar falls reduction interventions
      cannot be recommended based on the results of this study.

PMID- 19767630
TI  - Impairment of endogenous melatonin rhythm is related to the degree of chronic
      kidney disease (CREAM study).
AB  - BACKGROUND: The nocturnal endogenous melatonin rise, which is associated with the
      onset of sleep propensity, is absent in haemodialysis patients. Information on
      melatonin rhythms in chronic kidney disease (CKD) is limited. Clear relationships
      exist between melatonin, core body temperature and cortisol in healthy subjects.
      In CKD, no data are available on these relationships. The objective of the study
      was to characterize the rhythms of melatonin, cortisol and temperature in
      relation to renal function in patients with CKD. METHODS: From 28 patients (mean
      age 71 years) with various degrees of renal function, over a 24-h period, blood
      samples were collected every 2 h. An intestinal telemetric sensor was used to
      measure core temperature. The presence of diurnal rhythms was examined for
      melatonin, temperature and cortisol. Correlation analysis was performed between
      Cockcroft-Gault GFR (GFR), melatonin, cortisol and temperature parameters.
      RESULTS: The mean GFR was 57 +/- 30 ml/min. The subjects exhibited melatonin (n =
      24) and cortisol (n = 22) rhythms. GFR was significantly correlated to melatonin
      amplitude (r = 0.59, P = 0.003) and total melatonin production (r = 0.51, P =
      0.01), but not to temperature or cortisol rhythms. Interestingly, no associations
      were found between the rhythms of temperature, melatonin and cortisol.
      CONCLUSIONS: As melatonin amplitude and melatonin rhythm decreased with advancing
      renal dysfunction, follow-up research into circadian rhythms in patients with CKD
      is warranted.

PMID- 19767631
TI  - Nocturnal versus conventional haemodialysis: some current issues.

PMID- 19767632
TI  - Effect of icodextrin dialysis solution on body weight and fat accumulation over
      time in CAPD patients.
AB  - BACKGROUND: The purpose of this study was to analyse the changes of body
      composition and the effects of icodextrin dialysis solution over time on
      peritoneal dialysis (PD) in continuous ambulatory peritoneal dialysis (CAPD)
      patients. METHODS: Among 183 incident patients, 75 patients finished a complete
      36-month protocol. Clinical indices including daily glucose absorption and body
      composition, by bioelectrical impedance analysis (BIA), were measured in both
      groups (icodextrin group: 36 patients, non-icodextrin group: 39 patients) at the
      1st (baseline), 12th, 24th and 36th months. RESULTS: There were significant
      increases in body weight and fat mass during the 36 months after initiation of
      CAPD. It was found that 78% of 3 years of weight gain occurred during the first
      year and 88% of weight gain at the end of the first year was fat mass gain. The
      icodextrin group showed a significantly lower percent of fat mass during the
      first 36 months (P < 0.05) and also less changes in body weight, fat mass,
      percent (%) fat mass, visceral fat area and waist/hip ratio at 1, 2 and 3 years
      than the non-icodextrin group. There were no significant changes in total body
      water (TBW), extra cellular fluid (ECF), oedema index and lean body mass (LBM)
      through comparable daily and ultrafiltration volume (UFV) between the two groups
      during the initial 3 years. Factors associated with the higher percent of fat
      mass gain over time on peritoneal dialysis were age, diabetes, gender (female)
      and non-icodextrin group (all, P < 0.01, generalized estimating equation).
      CONCLUSION: The application of icodextrin solution may be a better option to
      alleviate excessive fat gain over time for patients on PD.

PMID- 19767633
TI  - Nail changes in kidney transplant recipients.
AB  - BACKGROUND: Nail changes are common complications of end-stage renal disease, and
      reports of nail changes in kidney transplant recipients (KTR) are rare. Few
      reports have documented a higher prevalence of onychomycosis in KTR compared with
      controls, while others found no significant differences. In this study, we
      investigated the prevalence and nature of nail changes in a large series of KTR.
      METHODS: Three hundred and two KTR (216 males and 86 females) were included in
      this study, and the mean transplant duration was 6.57 years (range 1.5 month-23
      years). They were screened for the presence of nail changes. Nail clippings were
      collected when indicated and cultures were performed for patients with suspected
      onychomycosis. The patients were compared with 302 age- and sex-matched healthy
      controls (220 males and 82 females). RESULTS: One hundred and twenty-one KTR
      (40.1%) had nail changes compared with 104 (34.4%) in controls. Onychomycosis,
      Muehrcke's nail and leuconychia were significantly more common in KTR [23 (7.6%),
      13.3 (4.3%), 11 (3.6%), respectively] compared with controls [7 (2.3%), 1(0.3%),
      2 (0.66%), P = 0.002, 0.001 and 0.02, respectively]. However, the most frequent
      nail change among KTR and controls was absent lunula, 90 (29.8%) and 80 (26.5%),
      respectively P = 0.36. Longitudinal ridging was also a frequent nail pathology
      among KTR and controls, 21 (6.9%) and 19 (6.3%), respectively, P = 0.74.
      CONCLUSION: KTR have higher prevalence rates of onychomycosis, Muehrcke's nail
      and leuconychia than the healthy population. On the other hand, absent lunula
      could be a normal variation among Egyptian people.

PMID- 19767634
TI  - Presentation and survival of patients with severe acute kidney injury and
      multiple myeloma: a 20-year experience from a single centre.
AB  - BACKGROUND: Myeloma is the second most common haematological malignancy and is a
      cause of severe acute kidney injury (serum creatinine >or=500 micromol/L) that
      has long been associated with a poor prognosis, although previous series have
      been small. METHODS: We have therefore documented the natural history of all 107
      patients referred to a large regional renal unit over a 20-year period and
      investigated factors associated with survival over a long period of time using
      Cox regression methods. RESULTS: Three factors were found to be significantly and
      independently associated with survival: use of chemotherapy [hazard ratio (HR)
      0.21, 95% CI: 0.08-0.46, P < 0.001], serum albumin (HR 0.49, 95% CI: 0.29-0.82, P
      = 0.02 for >or=35 g/L versus <35 g/L) and dialysis independence (HR 0.43, 95% CI:
      0.24-0.76, P = 0.005). However, survival was not found to be better for patients
      presenting in the second decade compared to the first (HR 0.88, 95% CI: 0.52
      1.50, P = 0.65). CONCLUSIONS: This analysis highlights the need for clinical
      trials of novel chemotherapy regimens in this complicated group of patients.
      Furthermore, whether strategies to restore or preserve dialysis-independent renal
      function provide additional benefit to effective chemotherapy also requires
      further investigation. The advent of efficacious low toxicity chemotherapy (such
      as thalidomide and bortezomib) and new dialysis techniques to remove free light
      chains may radically alter the outcome of this group of patients.

PMID- 19767635
TI  - NSF after Gadovist exposure: a case report and hypothesis of NSF development.
AB  - So far no cases of nephrogenic systemic fibrosis (NSF) have been published on
      macrocyclical gadolinium-based contrast media (Gd-CM), assumed as low NSF risk CM
      due to their complex stability. In our haemodialysis-dependent patient, the first
      symptoms indicating NSF appeared about 16 months after the exposure to Gadovist,
      a macrocyclical Gd-CM, and 1 month after x-ray angiography with iodinated CM
      (Ultravist). This indicates that in addition to excretory renal failure and Gd-CM
      exposure, the loss of biosynthetic renal function could be essential for NSF
      development. A hypothesis of possible pathways involved in the development of NSF
      is presented.

PMID- 19767636
TI  - Outbreak of tuberculosis caused by Mycobacterium bovis in golden Guernsey goats
      in Great Britain.
AB  - An outbreak of caprine tuberculosis caused by Mycobacterium bovis was disclosed
      in June 2008, affecting goats of the golden Guernsey breed kept on 10 separate
      smallholdings in south-west Wales and the west of England. Following the initial
      diagnosis at postmortem examination, 30 goats that reacted positively to the
      single intradermal comparative cervical tuberculin (SICCT) test, together with
      five in-contact animals, were euthanased and subjected to postmortem examination
      and mycobacterial culture. Spoligotyping and variable number tandem repeat
      analysis of isolates showed that they were all of the same genotype, endemic to
      south-west Wales. Retrospective movement tracings identified a goat herd in south
      west Wales, by then completely dispersed, as the probable common source of
      infection. There was a perfect correlation between the SICCT test and culture
      results in all slaughtered goats. Grossly visible tubercular lesions were
      observed at postmortem examination in all but one reactor.

PMID- 19767637
TI  - Use of tylvalosin-medicated feed to control porcine proliferative enteropathy.
AB  - The effect of an oral treatment with the tartrate salt of tylvalosin on the
      development of proliferative enteropathy in 60 experimentally challenged pigs was
      studied. Thirty of the pigs were fed a diet medicated with 50 ppm tylvalosin and
      30 were fed the unmedicated diet. The treated animals started to receive the
      medicated feed the day before they were inoculated, and continued to receive it
      for 14 days. The pigs' bodyweight, feed consumption and clinical signs were
      evaluated, and they were examined postmortem 20 days after inoculation, and
      samples of ileum were collected for immunohistochemistry (IHC) for Lawsonia
      intracellularis. Clinical signs of the disease were more evident in the untreated
      group than in the treated group. The average daily weight gain, average daily
      feed consumption and feed conversion efficiency were better in the treated group.
      The combined length of intestine with lesions was 2847 cm in the untreated group
      and 183 cm in the treated group. The tylvalosin treatment significantly reduced
      the level of L intracellularis infection; almost half of the treated pigs were
      IHC-negative compared with 3.3 per cent of the untreated pigs.

PMID- 19767638
TI  - Seasonal and age-related seroprevalence of Leptospira species in pigs in Korea.

PMID- 19767639
TI  - Use of a novel surgical approach to manage macerated fetus in a crossbred cow.

PMID- 19767640
TI  - Illthrift in suckling lambs attributed to lung pyogranuloma formation.

PMID- 19767641
TI  - Mycotic osteomyelitis caused by Schizophyllum commune in a dog.

PMID- 19767642
TI  - Black disease in a forest reindeer (Rangifer tarandus fennicus).

PMID- 19767643
TI  - Administration of micotil.

PMID- 19767644
TI  - Clostridial myocarditis in a scimitar-horned oryx.

PMID- 19767645
TI  - Retraction. Directional gene movement from human-pathogenic to commensal-like
      streptococci.

PMID- 19767646
TI  - Metal ion selectivity and substrate inhibition in the metal ion chelation
      catalyzed by human ferrochelatase.
AB  - Protoporphyrin IX ferrochelatase (EC 4.99.1.1) catalyzes the terminal step in the
      heme biosynthetic pathway, the insertion of ferrous iron into protoporphyrin IX.
      Ferrochelatase shows specificity, in vitro, for multiple metal ion substrates and
      exhibits substrate inhibition in the case of zinc, copper, cobalt, and nickel.
      Zinc is the most biologically significant of these; when iron is depleted, zinc
      porphyrins are formed physiologically. Examining the k(cat)/K(m)(app) ratios for
      zinc and iron reveals that, in vitro, zinc is the preferred substrate at all
      concentrations of porphyrin. This is not the observed biological specificity,
      where zinc porphyrins are abnormal; these data argue for the existence of a
      specific iron delivery mechanism in vivo. We demonstrate that zinc acts as an
      uncompetitive substrate inhibitor, suggesting that ferrochelatase acts via an
      ordered pathway. Steady-state characterization demonstrates that the apparent
      k(cat) depends on zinc and shows substrate inhibition. Although porphyrin
      substrate is not inhibitory, zinc inhibition is enhanced by increasing porphyrin
      concentration. This indicates that zinc inhibits by binding to an enzyme-product
      complex (EZnD(IX)) and is likely to be the second substrate in an ordered
      mechanism. Our analysis shows that substrate inhibition by zinc is not a
      mechanism that can promote specificity for iron over zinc, but is instead one
      that will reduce the production of all metalloporphyrins in the presence of high
      concentrations of zinc.

PMID- 19767647
TI  - Three redox states of Trypanosoma brucei alternative oxidase identified by
      infrared spectroscopy and electrochemistry.
AB  - Electrochemistry coupled with Fourier transform infrared (IR) spectroscopy was
      used to investigate the redox properties of recombinant alternative ubiquinol
      oxidase from Trypanosoma brucei, the organism responsible for African sleeping
      sickness. Stepwise reduction of the fully oxidized resting state of recombinant
      alternative ubiquinol oxidase revealed two distinct IR redox difference spectra.
      The first of these, signal 1, titrates in the reductive direction as an n = 2
      Nernstian component with an apparent midpoint potential of 80 mV at pH 7.0.
      However, reoxidation of signal 1 in the same potential range under anaerobic
      conditions did not occur and only began with potentials in excess of 500 mV.
      Reoxidation by introduction of oxygen was also unsuccessful. Signal 1 contained
      clear features that can be assigned to protonation of at least one carboxylate
      group, further perturbations of carboxylic and histidine residues, bound
      ubiquinone, and a negative band at 1554 cm(-1) that might arise from a radical in
      the fully oxidized protein. A second distinct IR redox difference spectrum,
      signal 2, appeared more slowly once signal 1 had been reduced. This component
      could be reoxidized with potentials above 100 mV. In addition, when both signals
      1 and 2 were reduced, introduction of oxygen caused rapid oxidation of both
      components. These data are interpreted in terms of the possible active site
      structure and mechanism of oxygen reduction to water.

PMID- 19767648
TI  - Ligand and substrate migration in human indoleamine 2,3-dioxygenase.
AB  - Human indoleamine 2,3-dioxygenase (hIDO), a monomeric heme enzyme, catalyzes the
      oxidative degradation of L-Trp and other indoleamine derivatives. Using Fourier
      transform infrared and optical absorption spectroscopy, we have investigated the
      interplay between ferrous hIDO, the ligand analog CO, and the physiological
      substrate L-Trp. These data provide the long sought evidence for two distinct L
      Trp binding sites. Upon photodissociation from the heme iron at T > 200 K, CO
      escapes into the solvent. Concomitantly, L-Trp exits the active site and,
      depending on the l-Trp concentration, migrates to a secondary binding site or
      into the solvent. Although L-Trp is spectroscopically silent at this site, it is
      still noticeable due to its pronounced effect on the CO association kinetics,
      which are significantly slower than those of L-Trp-free hIDO. L-Trp returns to
      its initial site only after CO has rebound to the heme iron.

PMID- 19767649
TI  - The prion protein: friend and foe.

PMID- 19767651
TI  - Prion protein: orchestrating neurotrophic activities.
AB  - PrP(C) is highly expressed in both the central and peripheral nervous systems
      from early stages of development and in adulthood. Its major conformational
      change and conversion into an abnormal form (PrP(Sc)) has been associated with
      the generation of prions, the infectious agent of transmissible spongiform
      encephalopathies (TSEs). The massive neurodegeneration presented by individuals
      suffering from these diseases has been associated with the gain of neurotoxic
      activity of PrP(Sc). On the other hand, major neurodegeneration is also observed
      in transgenic mice expressing PrP(C) molecules deleted of specific domains, which
      points to important functional domains within this molecule, and supports the
      hypothesis that loss-of PrP(C) function may contribute to the pathogenesis of
      TSEs. Furthermore, a large body of data demonstrates direct or indirect
      interaction of PrP(C) with extracellular matrix proteins, soluble factors,
      transmembrane proteins, G-protein coupled receptors and ions channels. The
      ability of PrP(C) to drive the assembly of multi-component complexes at the cell
      surface is likely the basis for its neurotrophic functions. These properties
      indicate that PrP(C) may be relevant for not only the spongiform
      encephalopathies, but also as an ancillary component of the pathogenesis of other
      neurodegenerative diseases, and therefore amenable to therapeutic targeting.

PMID- 19767650
TI  - Prion neurotoxicity: insights from prion protein mutants.
AB  - The chemical nature of prions and the mechanism by which they propagate are now
      reasonably well understood. In contrast, much less is known about the identity of
      the toxic prion protein (PrP) species that are responsible for neuronal death,
      and the cellular pathways that these forms activate. In addition, the normal,
      physiological function of cellular PrP (PrP(C)) has remained mysterious,
      hampering efforts to determine whether loss or alteration of this function
      contributes to the disease phenotype. Considerable evidence now suggests that
      aggregation, toxicity, and infectivity are distinct properties of PrP that do no
      necessarily coincide. In this review, we will discuss several mutant forms of PrP
      that produce spontaneous neurodegeneration in humans and/or transgenic mice
      without the formation of infectious PrP(Sc). These include an octapeptide
      insertional mutation, point mutations that favor synthesis of transmembrane forms
      of PrP, and deletions encompassing the central domain whose neurotoxicity is
      antagonized by the presence of wild-type PrP. By isolating the neurotoxic effects
      of PrP from the formation of infectious prions, these mutants have provided
      important insights into possible pathogenic mechanisms. These studies suggest
      that prion neurotoxicity may involve subversion of a cytoprotective activity of
      PrP(C) via altered signaling events at the plasma membrane.

PMID- 19767652
TI  - Autophagy, prion infection and their mutual interactions.
AB  - Prion diseases are infectious and fatal neurodegenerative disorders of man and
      animals which are characterized by spongiform degeneration in the central nervous
      system. Prion propagation involves the endocytic pathway and endosomal and
      lysosomal compartments are implicated in trafficking and re-cycling as well as
      final degradation of prions. Shifting the equilibrium between propagation and
      lysosomal clearance to the latter impairs cellular prion load. This and earlier
      findings of autophagic vacuoles in correlation to prion infections both in in
      vitro and in vivo studies prompted us and others to analyze the role of autophagy
      in prion infection. Autophagy is a fundamental cellular bulk degradation process
      for e.g. organelles or cytoplasmic proteins which has many implications for
      physiology and patho-physiology of cells and whole organisms. In various
      neurodegenerative disease models mainly protective functions of autophagy were
      recently described. In this review, we focus on recent findings which correlate
      autophagy and its manipulations with prion infection scenarios, and discuss
      perspectives and future directions. The findings summarized here add to the
      knowledge of the role of autophagy in neurodegeneration and provide interesting
      new insight into how non-cytosolic aggregated proteins might be subjected to
      autophagic clearance.

PMID- 19767653
TI  - Prion protein and metal interaction: physiological and pathological implications.
AB  - Metal induced free radicals are important mediators of neurotoxicity in several
      neurodegenerative conditions such as Alzheimer's disease, Parkinson's disease,
      and Huntington's disease. Similar evidence is now emerging for prion diseases, a
      group of neurodegenerative disorders of humans and animals. The main pathogenic
      agent in all prion disorders is PrP-scrapie (PrP(Sc)), a beta-sheet rich isoform
      of a normal cell surface glycoprotein known as the prion protein (PrP(C)).
      Deposits of PrP(Sc) in the brain parenchyma are believed to induce neurotoxicity
      through poorly understood mechanisms. Recent reports suggest that imbalance of
      brain metal homeostasis is a significant cause of PrP(Sc)-associated
      neurotoxicity, though the underlying mechanisms are difficult to explain based on
      existing information. Proposed hypotheses include a functional role for PrP(C) in
      metal metabolism, and loss of this function due to aggregation to the disease
      associated PrP(Sc) form as the cause of brain metal imbalance. Other views
      suggest gain of toxic function by PrP(Sc) due to sequestration of PrP(C)
      associated metals within the aggregates, resulting in the generation of redox
      active PrP(Sc) complexes. The physiological implications of some PrP(C)-metal
      interactions are known, while others are still unclear. The pathological
      implications of PrP(C)-metal interaction include metal-induced oxidative damage,
      and in some instances conversion of PrP(C) to a PrP(Sc)-like form. Despite its
      significance, only limited information is available on PrP-metal interaction and
      its implications on prion disease pathogenesis. In this review, we summarize the
      physiological significance and pathological implications of PrP-metal interaction
      on prion disease pathogenesis.

PMID- 19767654
TI  - Targeting of the prion protein to the cytosol: mechanisms and consequences.
AB  - Prion diseases are characterized by the conformational transition of the cellular
      prion protein (PrP(C)) into an aberrant protein conformer, designated scrapie
      prion protein (PrP(Sc)). A causal link between protein misfolding and
      neurodegeneration has been established for a variety of neurodegenerative
      disease, such as Alzheimer's disease, Parkinson's disease and polyglutamine
      diseases, but there is an ongoing debate about the nature of the neurotoxic
      species and how non-native conformers can damage neuronal populations. PrP is
      normally imported into the endoplasmic reticulum (ER) and targeted to the outer
      leaflet of the plasma membrane via a glycosylphosphatidylinositol (GPI) anchor.
      However, several conditions, such as ER stress or some pathogenic mutations in
      the PrP gene, can induce the mislocalization of PrP in the cytosol, where it has
      a neurotoxic potential as demonstrated in cell culture and transgenic mouse
      models. In this review we focus on intrinsic factors and cellular pathways
      implicated in the import of PrP into the ER and its mistargeting to the cytosol.
      The findings summarized here not only reveal a complex regulation of the
      biogenesis of PrP, but also provide interesting new insight into toxic activities
      of pathogenic protein conformers and quality control pathways of ER-targeted
      proteins.

PMID- 19767655
TI  - The role of GPI-anchored PrP C in mediating the neurotoxic effect of scrapie
      prions in neurons.
AB  - There are two central phenomena in prion disease: prion replication and prion
      neurotoxicity. Underlying them both is the conversion of a host-encoded
      ubiquitously expressed protein, prion protein (PrP(C)), into a partially-protease
      resistant isoform, PrP(Sc), which accumulates in the brain. PrP(Sc) is associated
      with both pathology and infectivity. In the absence of PrP(C), PrP(Sc) cannot be
      generated and PrP-null mice do not propagate infectivity or develop pathology on
      infection with scrapie. However, while PrP(C) expression is fundamental to both
      prion infectivity and neurodegeneration, the uncoupling of these processes is a
      growing concept in the field. This dissociation is evident in subclinical states
      of prion infection, where PrP(Sc) levels are high in the absence of disease, and
      in transgenic mice experiments, where, despite extra-neuronal PrP(Sc)
      accumulation, even in very high amounts, there is no neurotoxicity. Both these
      models have further implications. Thus depleting PrP(C) from neurons (but not
      glia) of prion-infected mice prevents clinical disease, and detaching it from the
      surface of cells by removing its anchor does the same. The uncoupling toxicity
      and infectivity has implications for the nature of the neurotoxic species; these
      mouse models suggest that the site for the generation of this species is intra
      neuronal. This review considers the role of neuronal surface-expressed PrP(C) in
      mediating toxicity in prion infection, and the dissociation of this from the
      deposition of PrP(Sc).

PMID- 19767656
TI  - Monoclonal antibodies in the treatment of non-Hodgkin's lymphoma: moving targets.

PMID- 19767658
TI  - Assisted reproductive technologies to establish pregnancies in couples with an
      HIV-1-infected man.
AB  - For HIV -1-infected men and women the introduction of highly active
      antiretroviral therapy (HART) in 1996 led to a spectacular increase in life
      expectancy and quality of life. In Western society where HART is readily
      available, HIV -1 is now considered to be a chronic disease and as a consequence
      quality of life is an important aspect for men and women with HIV-1. Many of them
      express the desire to father or mother a child. Assisted reproductive
      technologies, including intrauterine insemination (IUI), in vitro fertilisation
      (IVF) and intracytoplasmatic sperm injection (ICSI) in combination with semen
      washing have been used to decrease the risk of HIV -1 transmission in HIV-1
      infected discordant couples with an HIV-1-infected man. This article aims to
      summarise the current state of the art of assisted reproductive technologies for
      couples with an HIV -1-infected man and to discuss current trends and dilemmas in
      the treatment of these couples.

PMID- 19767657
TI  - Novel antibodies in the treatment of non-Hodgkin's lymphoma.
AB  - Monoclonal antibodies (mAbs) have revolutionised the treatment of malignancies,
      especially non-Hodgkin's lymphoma (NHL). Antibody-based therapies target tumour
      cells expressing a specific antigen while sparing the majority of normal cells
      leading to a decrease in treatment-associated toxicity. Rituximab, a monoclonal
      antibody directed against CD20 on B cells, was the first monoclonal antibody to
      be approved by the US Food and Drug Association (FDA) in 1997 for the treatment
      of patients with relapsed/refractory, follicular or low-grade NHL . However, it
      was soon realised that not all patients respond to rituximab therapy and close to
      60% of patients with follicular lymphoma who were previously sensitive to
      rituximab become 'resistant' to repeat rituximab therapy. This led to further
      attempts to improve the antitumour activity of anti-CD20 mAbs (i.e. 2nd/3rd
      generation anti-CD20s), and to identify additional potential targets on lymphoma
      cells other than CD20. A number of these antibodies directed against lymphoma
      cell targets other than CD20 are now undergoing development, many of which are
      currently in clinical trials. This manuscript focuses on an overview of these
      'non-anti-CD20' novel mAbs for NHL.

PMID- 19767659
TI  - Where the immune response meets the vessel wall.
AB  - Immune-mediated inflammatory diseases (IMIDs), including rheumatoid arthritis and
      spondyloarthritis, are associated with increased cardiovascular morbidity and
      mortality, independent of the established cardiovascular risk factors. The
      chronic inflammatory state, a hallmark of IMIDs, is considered to be a driving
      force for accelerated atherogenesis. Consequently, aggressive control of disease
      activity has been suggested to be instrumental for cardiovascular risk reduction.
      Specific guidelines for cardiovascular risk reduction in patients with IMIDs,
      particularly rheumatoid arthritis, are lacking, largely due to the absence of
      randomised clinical trial data. In this review, we focus on pathophysiology and
      observational evidence of cardiovascular risk in different prototypes of IMIDs.

PMID- 19767660
TI  - Intermitting umbilical pain, fever and weight loss in an otherwise healthy 65
      year-old male.

PMID- 19767661
TI  - An ulcer of the foot.

PMID- 19767662
TI  - Periorbital oedema.

PMID- 19767663
TI  - Purple urine bag syndrome.

PMID- 19767664
TI  - Blood pressure response to moderate physical activity is increased in obesity.
AB  - OBJECTIVE: To test the hypothesis that in young, normotensive obese subjects,
      physical activity at a fixed, moderate workload, causes a more pronounced
      hypertensive effect than in lean subjects. PATIENTS AND METHODS: 24 subjects (12
      with BMI >30 kg/m(2), 12 with BMI <25 kg/m(2)), underwent a moderate-intensity
      physical activity protocol (cycling at 100 W). Blood pressure and oxygen
      consumption were monitored continuously. RESULTS: In the obese subjects, physical
      activity caused a more pronounced increase in both systolic blood pressure
      (increase of 40.4 +/- 15.3 mmHg vs 21.2 +/- 10.2 mmHg in lean subjects; p=0.001)
      and diastolic blood pressure (17.5 +/- 17.9 mmHg vs 3.2 +/- 8.1 mmHg in lean
      subjects; p=0.02). In regression analyses, these differences were only partly
      explained by small differences in resting blood pressure. CONCLUSION: Healthy
      obese subjects show an enhanced prohypertensive response of both systolic and
      diastolic blood pressure to moderate-intensity physical activity.

PMID- 19767665
TI  - Complete remission of MDS RAEB following immunosuppressive treatment in a patient
      with Sweet's syndrome.
AB  - We report on a patient with myelodysplastic syndrome (MDS), classified as
      refractory anaemia with excess of blasts-2, and histiocytoid Sweet's syndrome.
      The skin lesions disappeared after initiation of corticosteroids and doxycycline.
      Remarkably, two months later a complete remission of the MDS occurred. Fourteen
      months later both the skin lesions and the MDS relapsed. Antileukaemic activity
      following reversion of the impaired cellular immunity due to an increased number
      of natural killer cells in his bone marrow may be responsible for this rare
      event. Inhibition of T-cell mediated myelosuppression by corticosteroids or a
      proapoptotic effect of doxycycline may have attributed as well.

PMID- 19767666
TI  - Splenectomy-induced long-term remission in a patient with multicentric
      Castleman's disease.
AB  - Castleman's disease (CD) is a rare lymphoproliferative disorder with a poorly
      understood pathogenesis. Multicentric CD can progress in different patterns, none
      of which can be cured with the current treatment options. We present a patient
      with multicentric CD in complete remission, eight years after a splenectomy
      without any other systemic treatment. We discuss the possible mechanism causing
      this long episode of complete remission in this patient.

PMID- 19767667
TI  - Improved survival for patients with large B-cell lymphoma after introduction of
      rituximab.
AB  - BACKGROUND: To determine whether the reported increase in survival of patients
      with diffuse large B-cell malignant lymphoma (DLBCL) after the introduction of
      rituximab is also seen in a non-academic hospital in the Netherlands. A
      retrospective study. METHODS: A dataset was made containing all newly diagnosed
      patients with DLBCL in a period of 2.5 years before until 2.5 years after
      introduction of rituximab in the standard treatment. Total follow-up time was 6.5
      years with a minimal follow-up of 18 months. RESULTS: The study population
      consisted of 65 patients; 32 in the prerituximab group (median follow-up time 60
      months) and 33 in the postrituximab group (median follow-up time 29 months).
      Progression-free survival increased significantly in the postrituximab group
      (hazard ratio 0.31; 95% CI 0.12 to 0.78; p=0.013; log rank p=0.008). The overall
      survival also showed a significant increase (p=0.048). The 18-month progression
      free survival increased from 59.4 to 81.8%; the overall survival at 18 months
      showed an increase from 65.5 to 81.8%. CONCLUSION: The introduction of rituximab
      in the treatment of DLB CL with CHOP chemotherapy has resulted in a significantly
      better prognosis for patients with DLBCL, treated in the Reinier de Graaf
      Gasthuis in Delft.

PMID- 19767668
TI  - The Dutch EPS Registry: increasing the knowledge of encapsulating peritoneal
      sclerosis.
AB  - Encapsulating peritoneal sclerosis (EPS) is a rare condition characterised by
      fibrotic thickening of the visceral peritoneum, leading to encapsulating of the
      intestines with partial or total intestinal obstruction. EPS is a serious
      complication of peritoneal dialysis (PD) with high morbidity and a mortality
      exceeding 50%. At present, there is uncertainty concerning the incidence and the
      risk factors involved in the development of EPS. To address these questions a
      nationwide registry has been initiated. The primary goals of the registry are to
      record the incidence of EPS and investigate the association of different
      variables, such as PD duration, medication, dialysis solutions and kidney
      transplantation with EPS. The registry will improve the knowledge of EPS and will
      serve to develop guidelines and necessary management strategies. From the
      registry different research activities can be initiated. A major challenge lies
      in the establishment of criteria that allow a timely diagnosis of EPS. At
      present, there are no diagnostic tools that can accurately detect EPS at an early
      stage. For this reason, besides patients with proven EPS, the clinical suspicion
      of EPS will be a sufficient criterion for inclusion in the registry. This
      nationwide EPS registry is currently enrolling patients.

PMID- 19767669
TI  - Responding to adverse events.

PMID- 19767670
TI  - The role of rituximab in a case of EBV-related lymphoproliferative disease
      presenting with haemophagocytosis.

PMID- 19767672
TI  - Comment on 'Estimating a modified Grubb's exponent in healthy human brains with
      near infrared spectroscopy and transcranial Doppler'.
AB  - The relationship between cerebral blood volume (CBV) and blood flow (CBF) has
      gained widespread interest because of its utility in using functional magnetic
      resonance imaging and optical imaging methods to estimate the cerebral metabolic
      rate of oxygen (CMRO(2)). A recent paper by Leung et al (2009 Physiol. Meas. 30 1
      12) nicely presents measurements relating CBV to cerebral blood flow velocity
      (CBFV) as measured by near infrared spectroscopy and transcranial Doppler,
      respectively. They suggest that this relationship cannot be inverted to estimate
      CBF (or CBFV) from CBV, and that doing so to estimate CMRO(2) is inappropriate.
      We argue that these data, and other related published data, do permit the
      estimation of CBF from CBV and thus enable CMRO(2) to be estimated when only
      measures of CBV and deoxygenated hemoglobin are available.

PMID- 19767673
TI  - Incommensurately modulated lanthanide coinage-metal diarsenides. I. CeAu(1
      delta)As2 [delta = 0.015 (2)]--a new distortion variant of the HfCuSi2 type with
      irregularly stacked cis-trans chains of arsenic atoms.
AB  - Rare-earth metal coinage-metal diarsenides LnTAs2 (Ln = Y, La, Ce-Lu; T = Cu, Ag,
      Au) are known to crystallize in structures closely related to the HfCuSi2 type,
      which comprises a stacking sequence of puckered TAs layers and planar square As
      nets, separated by the Ln atoms. CeAu(1-delta)As2, with delta = 0.015 (2), shows
      an incommensurate positional modulation of the arsenic atoms in the planar As
      nets. Based on X-ray diffraction data on a twinned crystal, a structure model in
      the monoclinic superspace group P12(1)/m1(alpha0gamma)00 (No. 11.1) with basic
      unit-cell parameters of a = 5.804 (1), b = 5.814 (1), c = 10.179 (1) A and beta =
      90.09 (8) degrees is presented. The components of the modulation wavevector q =
      alphaa* + 0b* + gammac* are alpha = 0.08 (1) and gamma = 0.39 (1). The structure
      comprises cis-trans chains and rectangles of As atoms and displays an intricate
      stacking sequence of the modulated arsenic nets. Rod groups and layer groups of
      the respective arrangements are identified and the arrangement of different
      motifs of the modulated As net is discussed.

PMID- 19767674
TI  - Incommensurately modulated lanthanide coinage-metal diarsenides. II. GdCuAs2,
      GdAu(1-delta)As2 and TbAu(1-delta)As2--new distortion variants of the HfCuSi2
      type with irregularly stacked zigzag chains of arsenic atoms.
AB  - GdCuAs2, GdAu(1-delta)As2 and TbAu(1-delta)As2 crystallize as incommensurately
      modulated variants of the HfCuSi2 type. Structure models have been developed in
      the monoclinic superspace group P12(1)/m1(alpha0gamma)00 (No. 11.1). The
      components of the modulation wavevectors q = alphaa* + 0b* + gammac* are alpha =
      0.04 (1) and gamma = 0.48 (1) for GdCuAs2, alpha = 0.03 (1) and gamma = 0.48 (1)
      for GdAu(1-delta)As2 and alpha = 0.02 (1) and gamma = 0.46 (1) for TbAu(1
      delta)As2. The predominant effect of the positional modulation is the distortion
      of a square net of arsenic atoms, which results in planar zigzag chains. Rod
      groups and layer groups of the respective structure motifs are identified and
      discussed.

PMID- 19767675
TI  - Modulation of atomic positions in CaCuxMn(7-x)O12 (x < or = 0.1).
AB  - The modulation of atomic positions in CaCu(x)Mn(7-x)O12 (x = 0 and 0.1) was
      studied using synchrotron radiation powder diffraction below 250 and 220 K,
      respectively. The copper-rich member CaCu(x)Mn(7-x)O12 (x = 0.23) does not show
      any modulation of the atomic positions at temperatures as low as 10 K. Using low
      temperature neutron powder diffraction the modulation of the magnetic moments of
      Mn ions in CaCu(x)Mn(7-x)O12 (x = 0, 0.1 and 0.23) has been investigated. Long
      range modulated magnetic ordering in CaCu(x)Mn(7-x)O12 (x = 0, 0.1 and 0.23) is
      observed below 90.4, 89.2 and 78.1 K. (0,0,q(p)) and (0,0,q(m)) are the
      propagation vectors describing the modulations of the atomic positions and the
      magnetic moments. For CaCu(x)Mn(7-x)O12 (x = 0 and 0.1) the magnetic modulation
      and atomic modulation lengths are related by a factor of 2 satisfying the
      relation (1-q(p)) = 2(1-q(m)).

PMID- 19767676
TI  - Modulated crystal structure of incommensurate low tridymite.
AB  - The incommensurately modulated crystal structure of low SiO2 tridymite was
      refined based on single-crystal X-ray diffraction data in the superspace group
      Cc(alpha0gamma)0. The data set consists of 885 main reflections, 1751 first
      order, 924 second-order and 119 third-order satellite reflections with I >
      3sigma(I). The modulation is mainly made up from cooperative twistings of the
      rigid SiO4 tetrahedra. Two orders of displacement waves are used to describe the
      modulation of the Si atoms and three orders for the O atoms. The maximal
      amplitudes are ca 0.6 A. O atoms bridging pairs of tetrahedra in cis and trans
      configurations show different positional modulation patterns. The anisotropic
      displacement parameters (ADPs) are also modulated. A correlation between ADP
      modulations and positional modulations was found.

PMID- 19767677
TI  - Structure of caesium disulfate at 120 and 273 K.
AB  - The crystal structures of Cs2S2O7 at 120 and 273 K have been determined from X
      ray single-crystal data. Caesium disulfate represents a new structure type with a
      uniquely high number of independent formula units at 120 K: In one part caesium
      ions form a tube surrounding the disulfate ions, [Cs8(S2O7)6+]n; in the other
      part a disulfate double-sheet sandwiches a zigzagging caesium ion chain,
      [Cs2(S2O7)6-]n. Caesium disulfate shows an isostructural order-disorder
      transition between 230 and 250 K, where two disulfate groups become partially
      disordered above 250 K. The Cs+-ion arrangement shows a remarkable similarity to
      the high-pressure Rb(IV) metal structure.

PMID- 19767678
TI  - Order-disorder of oxygen anions and vacancies in solid solutions of La2TiO5 and
      La4Ga2O9.
AB  - Successful Rietveld refinements of seven compounds with the formulae La2Ti((1
      x))Ga(x)O((5-x/2)), where x = 0.00, 0.20, 0.50, 0.70, 0.90, 0.95 and 1.00, were
      performed in order to describe the solid solubility between orthorhombic (Pnam)
      La2TiO5 and monoclinic (P2(1)/c) La4Ga2O9. The relationship between the end
      member structures, which are already known, is discussed; the space-group change
      is a consequence of ordering the oxygen vacancies that become more numerous as Ga
      is substituted for Ti. The structures of the solid solutions are also described.
      The lengths of cell edges obey Vegard's rule.

PMID- 19767679
TI  - Eu3Si(15-x)Al(1 + x)OxN(23-x) (x approximately 5/3) as a commensurate composite
      crystal.
AB  - A new Eu-SiAlON crystal, Eu3Si(15-x)Al(1 + x)O(x)N(23-x) (x approximately 5/3),
      was found and the structure was determined by an X-ray diffraction technique
      using a twinned sample. The structure consists of a host framework, which is
      constructed by the connection of MX4 tetrahedra (M: Si or Al; X: O or N), and Eu
      ions as the guest ions. The structure is considered to be a commensurate
      composite crystal. The basic vectors are a1 = a/3, b and c for the first
      substructure, and a2 = a/5, b and c for the second substructure. The first
      substructure consists of part of the host framework and the Eu ions, while the
      remainder of the host structure is taken as the second substructure. Possible
      phases belonging to the series are proposed using the composite crystal model in
      (3 + 1)-dimensional superspace. Chemical composition, possible space groups, cell
      parameters, and the basic model for those phases are presented.

PMID- 19767680
TI  - Ternary fluorides BaMF4 (M = Zn, Mg and Mn) at low temperatures.
AB  - Ternary fluorides BaMF4 (M = Zn, Mg, Mn) have been studied in the temperature
      range from 300 to 10 K using synchrotron and laboratory powder and single-crystal
      diffraction. The first two compounds are stable down to 10 K, while the third one
      undergoes a phase transition to an incommensurately modulated structure at
      approximately 250 K. The modulated phase is stable down to 10 K. The magnetic
      anomalies at 45 and 27 K observed previously in BaMnF4 are exclusively reflected
      in the behavior of the gamma component of the q vector, which assumes an
      irrational value of approximately 0.395 A(-1) at the temperature corresponding to
      the onset of the magnetic ordering and then stays constant down to 10 K. Mn-Mn
      distances do not indicate any structural response to the magnetic ordering. The
      formation of the modulated phase can be explained on the basis of simple
      geometrical criteria. The incorporation of the large Mn cation in the octahedral
      sheets implies an increase of the cavity in which the Ba ion is incorporated.
      This leads to the formation of the modulated structure to adapt the coordination
      sphere around Ba in such a way that the bond-valence sums can be kept close to
      the ideal value of two. With further lowering of the temperature, the charge
      balance around the Ba ion requires an increasingly anharmonic character of the
      modulation function of Ba, until finally at 10 K a crenel-like shape is assumed
      for the modulation of this atom.

PMID- 19767681
TI  - Modulated structure and phase transitions of Sr10Ga6O19.
AB  - The crystal structure of Sr10Ga6O19 was investigated by in situ single-crystal X
      ray diffraction in the temperature range 298-673 K. At ambient conditions the
      compound shows a (3 + 1)-dimensional modulated structure in the superspace group
      C2/c(0beta0)s0 [a = 34.9145 (13), b = 7.9369 (2), c = 15.9150 (7) A and beta =
      103.551 (3) degrees] with a modulation wavevector of q = 0.4288 (2)b*. Whereas
      the presented structural model uses first-order harmonic modulation functions
      only, some features of the modulations are discussed utilizing an electron
      density derived by the maximum entropy method. Furthermore, two phase transitions
      were identified: between 453 and 503 K the incommensurate superstructure is
      replaced by a doubling of the a and b lattice constants, and between 503 and 673
      K a phase with the basic cell is formed, identical to alpha-Sr10Ga6O19. Under
      some cooling conditions crystals showing a combined diffraction pattern of both
      superstructures can be obtained. The relation of these results to alpha
      Sr10Ga6O19 [Kahlenberg (2001). J. Solid State Chem. 160, 421-429] is discussed.

PMID- 19767682
TI  - Superspace description of the modulated structure of the metal-salt-hybrid Bi(7
      delta)Ni2Br(5-2delta) (delta = 1/9).
AB  - The compound Bi(7-delta)Ni2Br(5-2delta) = (Bi3Ni)2[Bi(1-delta)Br4]Br(1-2delta)
      (delta = 1/9) is a sub-bromide of the intermetallic phase Bi3Ni. Its crystal
      structure contains metallic rods, 1infinity[Bi3Ni], which are embedded in a salt
      like matrix of bromido-bismuthate(III) and bromide anions. The non-stoichiometry
      originates from the variation of the number n of trans edge-sharing octahedra in
      the [Bi(n)Br(4n + 2)]((n + 2)-) oligomers (3 < or = n < or = 5), as well as from
      vacancies on the sites of the isolated Br atoms. The simplified structure is
      described in the orthorhombic space group Cmcm with a = 4.0660 (4), b = 23.305
      (3), c = 17.130 (2) A. It shows a statistical distribution of vacancies and
      orientational disorder of the concatenated octahedra. By choosing the modulation
      vector q = a*/9 + b*/2, the additional weak reflections of the diffraction
      pattern can be indexed. In the [3 + 1]-dimensional superspace group
      Pmnm(alpha(1/2)0)000, an ordered structure model is achieved. The modulated
      crystal structure bears a strong resemblance to the somewhat higher oxidized sub
      bromide Bi(7-delta)Ni2Br5 (delta = 1/9).

PMID- 19767683
TI  - Weak interactions in chain polymers [M(mu-X)2L2]infinity (M = Zn, Cd; X = Cl, Br;
      L = substituted pyridine)--an electron density study.
AB  - The experimental electron-density distributions in crystals of five chain
      polymers [M(mu-X)2(py)2] (M = Zn, Cd; X = Cl, Br; py = 3,5-substituted pyridine)
      have been obtained from high-resolution X-ray diffraction data sets (sin
      theta/lambda > 1.1 A(-1)) at 100 K. Topological analyses following Bader's 'Atoms
      in Molecules' approach not only confirmed the existence of (3, -1) critical
      points for the chemically reasonable and presumably strong covalent and
      coordinative bonds, but also for four different secondary interactions which are
      expected to play a role in stabilizing the polymeric structures which are unusual
      for Zn as the metal center. These weaker contacts comprise intra- and inter
      strand C-H...X-M hydrogen bonds on the one hand and C-X...X-C interhalogen
      contacts on the other hand. According to the experimental electron-density
      studies, the non-classical hydrogen bonds are associated with higher electron
      density in the (3, -1) critical points than the halogen bonds and hence are the
      dominant interactions both with respect to intra- and inter-chain contacts.

PMID- 19767684
TI  - [Ru(py)4Cl(NO)](PF6)2.0.5H2O: a model system for structural determination and ab
      initio calculations of photo-induced linkage NO isomers.
AB  - Structure analysis of ground state (GS) and two light-induced (SI and SII)
      metastable linkage NO isomers of [Ru(py)4Cl(NO)](PF6)2.0.5H2O is presented.
      Illumination of the crystal by a laser with lambda = 473 nm at T = 80 K transfers
      around 92% of the NO ligands from Ru-N-O into the isomeric configuration Ru-O-N
      (SI). A subsequent irradiation with lambda = 980 nm generates about 48% of the
      side-on configuration Ru<(N)(O) (SII). Heating to temperatures above 200 K or
      irradiation with light in the red spectral range transfers both metastable
      isomers reversibly back to the GS. Photodifference maps clearly show the N-O
      configurations for both isomers and they could be used to find a proper starting
      model for subsequent refinements. Both metastable isomers have slightly but
      significantly different cell parameters with respect to GS. The main structural
      changes besides the Ru-O-N and RU<(N)(O) linkage are shortenings of the trans Ru
      Cl bonds and the equatorial Ru-N bonds. The experimental results are compared
      with solid-state calculations based on density functional theory (DFT), which
      reproduce the observed structures with high accuracy concerning bond lengths and
      angles. The problem of how the different occupancies of SI and GS could affect
      refinement results was solved by a simulation procedure using the DFT data as
      starting values.

PMID- 19767685
TI  - Topological properties of hydrogen bonds and covalent bonds from charge densities
      obtained by the maximum entropy method (MEM).
AB  - Charge densities have been determined by the Maximum Entropy Method (MEM) from
      the high-resolution, low-temperature (T approximately 20 K) X-ray diffraction
      data of six different crystals of amino acids and peptides. A comparison of
      dynamic deformation densities of the MEM with static and dynamic deformation
      densities of multipole models shows that the MEM may lead to a better description
      of the electron density in hydrogen bonds in cases where the multipole model has
      been restricted to isotropic displacement parameters and low-order multipoles
      (l(max) = 1) for the H atoms. Topological properties at bond critical points
      (BCPs) are found to depend systematically on the bond length, but with different
      functions for covalent C-C, C-N and C-O bonds, and for hydrogen bonds together
      with covalent C-H and N-H bonds. Similar dependencies are known for AIM
      properties derived from static multipole densities. The ratio of potential and
      kinetic energy densities |V(BCP)|/G(BCP) is successfully used for a
      classification of hydrogen bonds according to their distance d(H...O) between the
      H atom and the acceptor atom. The classification based on MEM densities coincides
      with the usual classification of hydrogen bonds as strong, intermediate and weak
      [Jeffrey (1997). An Introduction to Hydrogen Bonding. Oxford University Press].
      MEM and procrystal densities lead to similar values of the densities at the BCPs
      of hydrogen bonds, but differences are shown to prevail, such that it is found
      that only the true charge density, represented by MEM densities, the multipole
      model or some other method can lead to the correct characterization of chemical
      bonding. Our results do not confirm suggestions in the literature that the
      promolecule density might be sufficient for a characterization of hydrogen bonds.

PMID- 19767686
TI  - Structure and conformational analysis of a bidentate pro-ligand, C21H34N2S2, from
      powder synchrotron diffraction data and solid-state DFTB calculations.
AB  - The molecular and crystalline structure of ethyl 1',2',3',4',4a',5',6',7'
      octahydrodispiro[cyclohexane-1,2'-quinazoline-4',1''-cyclohexane]-8'
      carbodithioate (I) was solved and refined from powder synchrotron X-ray
      diffraction data. The initial model for the structural solution in direct space
      using the simulated annealing algorithm implemented in DASH [David et al. (2006).
      J. Appl. Cryst. 39, 910-915] was obtained performing a conformational study on
      the fused six-membered rings of the octahydroquinazoline system and the two
      spiran cyclohexane rings of (I). The best model was chosen using experimental
      evidence from 1H and 13C NMR [Contreras et al. (2001). J. Heterocycl. Chem. 38,
      1223-1225] in combination with semi-empirical AM1 calculations. In the refined
      structure the two spiran rings have the chair conformation, while both of the
      fused rings in the octahydroquinazoline system have half-chair conformations
      compared with in-vacuum density-functional theory (DFT) B3LYP/6-311G*, DFTB
      (density-functional tight-binding) theoretical calculations in the solid state
      and other related structures from X-ray diffraction data. Compound (I) presents
      weak intramolecular hydrogen bonds of the type N-H...S and C-H...S, which produce
      delocalization of the electron density in the generated rings described by graph
      symbols S(6) and S(5). Packing of the molecules is dominated by van der Waals
      interactions.

PMID- 19767687
TI  - The experimental and theoretical QTAIMC study of the atomic and molecular
      interactions in dinitrogen tetroxide.
AB  - The atomic and molecular interactions in a crystal of dinitrogen tetraoxide,
      alpha-N2O4, have been studied in terms of the quantum topological theory of
      molecular structure using high-resolution, low-temperature X-ray diffraction
      data. The experimental electron density and electrostatic potential have been
      reconstructed with the Hansen-Coppens multipole model. In addition, the three
      dimensional periodic electron density of crystalline alpha-N2O4 has been
      calculated at the B3LYP/cc-pVDZ level of theory with and without the geometry
      optimization. The application of the quantum theory of atoms in molecules and
      crystals (QTAIMC) recovered the two types of intermolecular bond paths between O
      atoms in crystalline alpha-N2O4, one measuring 3.094, the other 3.116 A. The
      three-dimensional distribution of the Laplacian of the electron density around
      the O atoms showed that the lumps in the negative Laplacian fit the holes on the
      O atoms in the adjacent molecules, both atoms being linked by the intermolecular
      bond paths. This shows that the Lewis-type molecular complementarity contributes
      significantly to intermolecular bonding in crystalline N2O4. Partial overlap of
      atomic-like basins created by zero-flux surfaces in both the electron density and
      the electrostatic potential show that attractive electrostatic interaction exists
      between O atoms even though they carry the same net formal charge. The exchange
      and correlation contributions to the potential energy density were also computed
      by means of the model functionals, which use the experimental electron density
      and its derivatives. It was found that the intermolecular interactions in alpha
      N2O4 are accompanied by the correlation energy-density ;bridges' lowering the
      local potential energy along the intermolecular O...O bond paths in the electron
      density, while the exchange energy density governs the shape of bounded
      molecules.

PMID- 19767688
TI  - Early bone healing around implant surfaces treated with variations in the
      resorbable blasting media method. A study in rabbits.
AB  - OBJECTIVE: this study aimed to histomorphologically and histomorphometrically
      evaluate the in vivo response to three variations in the resorbable blasting
      media (RBM) surface processing in a rabbit femur model. STUDY DESIGN: screw root
      form implants with 3.75 mm in diameter by 8 mm in length presenting four surfaces
      (n=8 each): alumina-blasted/acid-etched (AB/AE), bioresorbable ceramic blasted
      (TCP), TCP + acid etching, and AB/AE + TCP were characterized by scanning
      electron microscopy (SEM) and atomic force microscopy (AFM). The implants were
      placed at the distal femur of 8 New Zeland rabbits, remaining for 2 weeks in
      vivo. After sacrifice, the implants were nondecalcified processed to 30 micro m
      thickness slides for histomorphology and bone-to-implant contact (BIC)
      determination. Statistical analysis was performed by one-way ANOVA at 95% level
      of significance considering implant surface as the independent variable and BIC
      as the dependent variable. RESULTS: SEM and AFM showed that all surfaces
      presented rough textures and that calciu-hosohate particles were observed at the
      TCP group surface. Histologic evaluation showed intimate interaction between
      newly formed woven bone and all implant surfaces, demonstrating that all surfaces
      were biocompatible and osseoconductive. Significant differences in BIC were
      observed between the AB/AE and the AB/AE + TCP, and intermediate values observed
      for the TCP and TCP + Acid surfaces. CONCLUSION: irrespective of RBM processing
      variation, all surfaces were osseoconductive and biocaompatible. The differences
      in BIC between groups warrant further bone-implant interface biomechanical
      characterization.

PMID- 19767689
TI  - Effect of calcium hydroxide dressing on microleakage of composite restorations in
      endodontically treated teeth subsequent to bleaching.
AB  - OBJECTIVE: This study evaluates the effect of calcium hydroxide dressing on
      microleakage of composite restorations following non-vital bleaching. METHODS: A
      total of 45 sound extracted human maxillary central incisors underwent endodontic
      treatment. The teeth were randomly divided into three groups (n=15). In group 1,
      access cavities were restored with composite. In group 2, the teeth underwent a
      bleaching procedure for one week before being restored with composite. In group
      3, following a bleaching procedure, calcium hydroxide paste was placed in the
      pulp chamber for one week. The teeth were then restored with composite. The
      specimens were subjected to a dye leakage test. The data was analyzed using
      Kruskal-Wallis and Mann-Whitney U tests. RESULTS: There were significant
      differences between the groups (P<0.0005). No statistically significant
      differences were found between groups 2 and 3, while the differences between
      other groups were significant. CONCLUSIONS: The bleaching agent increased
      microleakage of composite restorations in non-vital bleaching, whereas
      microleakage was not found to be increased by calcium hydroxide.

PMID- 19767690
TI  - Hybrid layers of etch-and-rinse versus self-etching adhesive systems.
AB  - OBJECTIVE: To evaluate the effectiveness in the formation of resin tags, adhesive
      lateral branches and hybrid layers of five adhesive systems, when bonding to
      dentine. MATERIAL AND METHODS: Flat dentin surfaces from 25 molars were bonded
      with several adhesive systems according to the manufacturers' instructions.
      Composite build-ups were constructed incrementally with Tetric Ceram. The
      Specimens were sectioned parallel to the long axis. One section was treated with
      phosphoric acid and sodium hypochlorite in order to reveal the hybrid layer
      formation. The other section was stored in 30% hydrochloric acid to detect resin
      tags and adhesive lateral branch formation. RESULTS: The two etch-and-rinse self
      priming adhesives exhibited thicker hybrid layers than those found in self
      etching adhesive systems. The all-in-one adhesive showed droplet formation
      between the adhesive and the resin composite. The resin tags formed with the etch
      and-rinse adhesives were much longer than those found with the self-etching
      adhesives. Lateral branch formation was observed in etch-and-rinse adhesives and
      in one of the self-etch adhesives Clearfil SE Bond (SEB). CONCLUSION: The formed
      hybrid layer obtained with the two-step self-etching adhesives and the etch-and
      rinse systems were continuous and uniform in thickness. Droplets within the all
      in-one adhesive layer may occur as a result of water absorption from dentin
      through osmosis, and may interfere with proper resin polymerization. Resin tags
      obtained with SEB and the etch-and-rinse adhesive systems showed lateral
      branches, which is a sign of proper resin infiltration.

PMID- 19767691
TI  - Implant treatment in patients with osteoporosis.
AB  - Osteoporosis is very common, particularly in post-menopausal women and is
      characterized by a decrease in bone mass and strength. Osteoporosis also affects
      the jawbone and it is considered a potential contraindication to placement of
      dental implants. The present paper reviews the literature regarding the effect of
      osteoporosis on osseointegration of implants. Experimental models have shown that
      osteoporosis affects the process of osseointegration, which can be reversed by
      treatment. However, studies in subjects with osteoporosis have shown no
      differences in survival of the implants compared to healthy individuals.
      Therefore, osteoporosis cannot be considered a contraindication for implant
      placement. Oral bisphosphonates are the most commonly used pharmacological agents
      in the treatment of osteoporosis. Although there have been cases of osteonecrosis
      of the jaw in patients treated with bisphosphonates, they are very rare and it is
      more usually associated with intravenous bisphosphonates in patients with
      neoplasms or other serious diseases. Nevertheless, patients treated with
      bisphosphonates must be informed in writing about the possibility of this
      complication and must give informed consent. Ceasing to use bisphosphonates
      before implant placement does not seem to be necessary.

PMID- 19767692
TI  - Adaptation and validation for Spain of the Child-Oral Impact on Daily Performance
      (C-OIDP) for use with adolescents.
AB  - OBJECTIVES: To linguistically and culturally adapt the Child-OIDP, an Oral Health
      Related Quality of Life (OHRQoL) index, into Spanish for use among adolescents,
      and to validate it by evaluating the psychometric properties of the self
      administered version. STUDY DESIGN: Following a forward - backward translation
      procedure, the English version of the questionnaire was translated by independent
      translators and the reconciled version was then sent to three experts for
      assessment. A pilot study was conducted on a sub-sample of 30 adolescents aged
      between 11 - 12 years to assess their understanding of the questionnaire and its
      wording. The participants in the main study comprised 425 school children aged
      from 11 to 14 and pertaining to the oral health survey on school children in
      Navarre; these children were given a clinical examination and answered a
      structured questionnaire on oral health self-perception, satisfaction and
      perceived dental treatment needs. We evaluated the content validity, face
      validity, criterion validity, internal consistency and reliability. RESULTS: With
      regard to the face validity, the experts' opinion was that the version was
      adequate. The pilot study indicated minor changes to the wording to better adapt
      it for the target population. Regarding criterion and construct validity, the
      association of the C-OIDP with the self-perception variables gave statistically
      significant results (p<0.01) in all cases. For the internal consistency analysis,
      no negative correlations were present in the correlations matrix nor were any of
      the values too high to become redundant; the majority were statistically
      significant (p<0.05). Cronbach's alpha value was 0.68, with corrected item-total
      values of between 0.20 and 0.56 and with no alpha if-item-deleted values greater
      than 0.68. The test-retest analysis gave an intraclass correlation coefficient
      (ICC)=0.98. CONCLUSION: The Spanish version of the self-administered
      questionnaire for the C-OIDP for adolescents adequately demonstrated successful
      psychometric properties and, therefore, is a valid and reliable instrument for
      measuring the OHRQoL of adolescents.

PMID- 19767693
TI  - Detection of Helicobacter pylori using PCR in dental plaque of patients with and
      without gastritis.
AB  - OBJECTIVES: Helicobacter pylori (H.pylori) accounts for gastritis, peptic ulcer
      and is a probable cause of gastric cancer. Since its detection in the oral
      cavity, concerns have been raised about dental plaque as a reservoir for
      reinfection. The aim of this study was to detect the organism in the dental
      plaque and to determine the association, if any, between H. pylori gastritis and
      dental plaque contamination causing H.pylori. STUDY DESIGN: A polymerase chain
      reaction-based method was used for detection of H. pylori in clinical specimens.
      Supra and subgingival samples were collected from 67 patients with chronic
      periodontitis, 23 of whom were also suffering from gastritis. The data were
      analyzed with Chi square and Fisher exact test and the statistical significance
      was set to 0.05. RESULTS: H.pylori was scarce in patients with
      periodontitis(5.9%). There was a significant association between the presence of
      H.pylori in the dental plaque and gastritis (p=0.012). CONCLUSIONS: Although
      rarely seen, H.pylori infected dental plaque may be a source for reinfection. It
      is therefore suggested that professional plaque removal and oral hygiene
      procedures be performed, along with the antibiotic treatment of H.pylori.

PMID- 19767694
TI  - Complications in third molar removal: a retrospective study of 588 patients.
AB  - OBJECTIVES: Surgical removal of third molars is a regular surgical procedure,
      which like all operations, may have complications. The purpose of the study was
      to analyze the incidence of complications and their relationship with the
      surgical difficulty in a group of 588 patients treated by the same oral and
      maxillofacial surgeon. STUDY DESIGN: This retrospective cohort study consisted of
      1699 third molars (M3) removed between 2005 and 2008. The teeth were grouped into
      a 6-class scale of surgical difficulty rated according to the surgical procedure
      description in the patient's file: I: upper M3 requiring forceps only; II: upper
      M3 requiring osteotomy; III: upper M3 requiring osteotomy and tooth section; IV:
      lower M3 requiring forceps only; V: lower M3 requiring osteotomy; VI: lower M3
      requiring osteotomy and tooth section. The complications were grouped into each
      surgical difficulty class and their incidence and management were also described.
      RESULTS: 59 complications (3.47%), including pain, root tip fracture,
      paresthesia, alveolar osteitis, temporomandibular joint discomfort, and oroantral
      fistula were reported. Surgical difficulty class VI presented the higher
      incidence of complications (n=38). CONCLUSIONS: The risk of complications in
      third molar surgery will always exist and increases in proportion to the surgical
      difficulty. Mandibular M3 requiring osteotomy and tooth section have the highest
      risk of complications.

PMID- 19767695
TI  - Epidemiologic profile and quality of life of patients treated for oral cancer in
      Juiz de Fora, Minas Gerais, Brazil.
AB  - OBJECTIVES: To assess the quality of life of patients treated for oral cancer,
      analyzing their physical, social/family, functional and emotional well-being; to
      identify socioeconomic and clinical functional variables that may potentially
      influence their quality of life; to describe the patients' epidemiologic profile
      (sex and age) and tumor features (histopathology, anatomical location and stage);
      to identify the frequency of risk factors associated with the malignancy. STUDY
      DESIGN: Observational cross-sectional study-case series study undertaken in 2
      cancer treatment institutions in Juiz de Fora, Minas Gerais, Brazil, between 2000
      and 2007. RESULTS: Of the 88 registered oral cancer patients, 16 were selected
      for the study sample. The majority of the study sample (87%) included males, with
      a mean age of 57.06 years; 43.8% were retired; 50% had not completed elementary
      education. Most (56.3%) had a monthly income of less than the minimum wage. Most
      (83.7%) smoked before cancer diagnosis and 43.8% from this sample continued to
      smoke after treatment. In addition, those who drank alcohol before treatment
      continued drinking (31.3%). The tongue was the predominant anatomic site (37.5%).
      The patients' quality of life score was fair; the best result was for emotional
      well-being. CONCLUSIONS: Despite the limitations imposed by low survival, it was
      possible to evaluate the quality of life of these patients. Patients having a
      family income higher than the minimum monthly wage scored significantly better in
      final indexes FACT-G and FACT-HN than those with a lower income.

PMID- 19767696
TI  - Porous titanium for biomedical applications: an experimental study on rabbits.
AB  - OBJECTIVE: The aim of this study was to carry out an in vivo assessment of bone
      ingrowth in two different types of porous titanium -the first being completely
      porous, and the second with a porous surface and dense nucleus, manufactured by
      powder metallurgy- and to evaluate their mechanical properties. STUDY DESIGN: Ten
      scaffolds from each group were submitted to metallographic analysis and
      compression tests. Next, two scaffolds of each type were inserted into 14
      rabbits, which were sacrificed 8 weeks after surgery. The samples were submitted
      for histological examination. RESULTS: Metallographic analysis revealed
      interconnected pores, and the average interconnected pore diameter was about 360
      mm, with 36% total porosity. The totally porous titanium samples and the titanium
      samples with porous surface and dense nucleus showed an average compressive
      strength of 16.19 MPa and 69.27 MPa, respectively. After 8 weeks, the animals
      showed bone ingrowth, even into the most internal pores. CONCLUSIONS: The pore
      morphology was effective in permitting bone ingrowth in both groups. Titanium
      scaffolds with a porous surface and dense nucleus showed the best mechanical
      properties and most adequate interface.

PMID- 19767697
TI  - Simultaneous occurrence of compound odontoma and arrested root formation as
      developmental disturbances after maxillofacial trauma: a case report.
AB  - Traumatic injury to a primary tooth and/or a bone fracture has the potential to
      damage the underlying permanent tooth germ which may disturb its development. The
      extent of the malformation depends on the developmental stage of the permanent
      tooth and the intensity of the trauma. The presence of infection may be a
      predictive factor for these abnormalities. Open surgical procedures can also
      potentially cause impaction and developmental disturbances. Several developmental
      alterations such as discolouration, hypoplasia, crown dilaceration, root
      angulation or dilaceration, sequestration of permanent tooth buds and disturbance
      in eruption have been reported in permanent teeth after trauma. However, odontoma
      like malformations and partial or complete arrest of root formation are rare
      complications developed after trauma. This article presents a rare case with
      simultaneous occurrence of an odontoma-like malformation and complete and partial
      arrested root formations as the results of maxillofacial trauma. Almost all
      pediatric fractures must be managed with closed reduction as much as possible.
      However, if it is necessary to perform an open reduction, careful attention must
      be paid during placement of the osteosynthetic plates and screws; and tooth bud
      development must be followed periodically.

PMID- 19767698
TI  - Meta-analysis of the etiology of odontogenic maxillary sinusitis.
AB  - OBJECTIVE: To identify and evaluate the frequency of the different odontogenic
      conditions that may lead to maxillary sinusitis. STUDY DESIGN: An observational
      and retrospective meta-analysis was carried out on 770 cases of maxillary
      sinusitis obtained from a literature review of 15 articles. RESULTS: Maxillary
      sinusitis most commonly manifests itself as chronic maxillary sinusitis. It is
      more common in females and is most often diagnosed in the fifth decade of life.
      The teeth most predominantly affected are the molars, with the first molar tooth
      being the most frequently involved. The principal etiological factor is
      extraction.

PMID- 19767699
TI  - Polyurethane and PTFE membranes for guided bone regeneration: histopathological
      and ultrastructural evaluation.
AB  - OBJECTIVE: The purpose of this study was to research a membrane material for use
      in guided bone regeneration. STUDY DESIGN: In this study, 25 male Wistar rats
      were used to analyze the biocompatibility and degradation process of
      biomembranes. The morphological changes in subcutaneous implantations were
      assessed after 7, 14, 21, 28 and 70 days. The materials were made of polyurethane
      polymer (AUG) obtained from vegetal oil (Ricinus communis) and
      polytetrafluoroethylene membrane (PTFE). The surface characteristics of the
      physical barriers in scanning electronic microscopic (SEM) were also evaluated.
      RESULTS: In both groups, the initial histological analysis showed moderate
      inflammatory infiltrate, which was predominantly polymorphonuclear. There was
      also a presence of edema, which was gradually replaced by granulation tissue,
      culminating in a fibrous capsule. In the AUG group, some multinucleated giant
      cells were present in the contact interface, with the space previously occupied
      by the material. However, membrane degradation was not observed during the period
      studied. According to the present SEM findings, porosity was not detected in the
      AUG or PTFE membranes. CONCLUSION: The researched material is biocompatible and
      the degradation process is extremely slow or may not even occur at all.

PMID- 19767700
TI  - Granulocytic sarcoma of the oral cavity in a chronic myeloid leukemia patient: an
      unusual presentation.
AB  - Intraoral granulocytic sarcoma is an unusual manifestation of chronic or acute
      leukemia. The oral manifestations often involve enlargements of the gingival and
      mucosal tissue from direct leukemic cell infiltration. Only 38 cases have been
      reported in scientific literature to date. We present the case of a 47 year-old
      female who was diagnosed with chronic myeloid leukemia (CML) in December 2006.
      She was referred to a dentist for further evaluation, revealing generalized
      gingival overgrowth as well as periodontal, apical disease, and bleeding of the
      gums. An oral biopsy was performed and histological features revealed immature
      blast-like cells.

PMID- 19767701
TI  - Osteolipoma of the buccal mucosa.
AB  - Lipomas are benign mesenchymal neoplasms of soft tissue that can be found in any
      part of the human body. Conversely, their presence in the oral mucosa is rather
      uncommon, with approximately 4% of the cases occurring in the oral cavity. In
      such cases, they are likely to have originated from mature adipose tissue and to
      be among several described histological variants of lipomas, which are identified
      according to the predominant type of tissue. There is a rare lipoma, known as an
      osteolipoma or an ossifying lipoma; however, little has been written this type of
      lipoma characterized by a classical lipoma with areas of osseous metaplasia.
      Considering the few cases of oral osteolipomas previously described in the
      English-related literature and the consequent risk of misdiagnosis and
      overtreatment, this paper describes an extreme case of an osteolipoma affecting
      the buccal mucosa of an adult patient. This paper focuses particularly on the
      pathogenesis of this lesion and the discussion of a correct diagnosis.

PMID- 19767702
TI  - Accuracy, sensitivity and specificity of fine needle aspiration biopsy in
      salivary gland tumours: a retrospective study.
AB  - OBJECTIVE: The aim of this study was to evaluate the diagnostic accuracy,
      sensitivity and specificity of fine needle aspiration biopsies (FNAB) of salivary
      gland tumours performed at the Erasto Gaertner Hospital over the course of a four
      year period. STUDY DESIGN: A retrospective study was carried out between 2001
      2005 to review the cases of patients with salivary gland tumours who had
      undergone pre-operative FNAB and had been diagnosed during post-operative
      histopathology examination. RESULTS: A total of 106 cases of salivary gland
      tumours were considered for this study, but 27 cases (25.5%) of the samples were
      considered unsatisfactory for analysis. The sensitivity, specificity and accuracy
      were calculated considering only the 79 benign and malignant cases in which FNAB
      provided sufficient samples for analysis. Based on these data, the value of
      sensitivity was 68.2% (15/22), specificity was 87.7% (50/57), accuracy was 82.3%
      (65/79), positive predictive value was 68.2% (15/22) and negative predictive
      value was 87.7% (50/57). CONCLUSIONS: Despite the high rate of inadequate samples
      obtained in the FNAB in this study, the technique offers high specificity,
      accuracy and acceptable sensitivity.

PMID- 19767703
TI  - Solitary fibrous tumor surrounding the carotid sheath.
AB  - Solitary fibrous tumors (SFTs) are rare spindle cell neoplasms that are mostly
      found arising from the pleura. Although SFTs recently have been reported in other
      regions, they are rare in the head and neck and have often been misdiagnosed due
      to their rarity. SFTs are benign in most cases. Clinically, SFTs usually manifest
      as well-circumscribed, slow-growing, smooth and painless masses. Symptoms are
      often minimal, although they may include sore throat, difficulty in swallowing,
      change of voice or trismus. CT-Scan and MRI are the most sensitive imaging
      procedures used. The treatment of choice is complete surgical excision of the
      lesion. Because recurrences have been noted up to 30 years after surgery, long
      term follow up is mandatory. In this article, we present a case of a Solitary
      Fibrous Tumor arising in the parapharyngeal space in a 20-year-old man, involving
      the carotid sheath, treated by surgical excision with no recurrence after 1 year.
      The clinical presentation, surgical management and pathological findings are
      described.

PMID- 19767704
TI  - Evaluation of cell proliferation rate in non-dysplastic leukoplakias.
AB  - OBJECTIVE: Analyze whether the most frequent cases of non-dysplastic
      leukoplakias, hyperkeratosis (H), acanthosis (A), and hyperkeratosis with
      acanthosis (HA) have similar cell proliferation rates and to compare them with
      epithelial dysplastic (ED) leukoplakias and normal oral epithelium (NOE). STUDY
      DESIGN: The sample comprised 10 cases of normal oral epithelium, 10 cases of
      hyperkeratosis, 10 cases of acanthosis, 10 cases of hyperkeratosis with
      acanthosis and 10 cases of epithelial dysplasia. The mean number of AgNORs per
      nucleus (mAgNOR) and the mean percentage of cells with 1, 2, 3 and 4 or more
      AgNORs per nucleus (pAgNOR) were recorded. RESULTS: The results of mAgNOR showed
      differences between disorders in the evaluation of the basal layer, of the
      parabasal layer, and in the overall evaluation. mAgNOR and pAgNOR=2 increased
      progressively from normal oral epithelium to hyperkeratosis with acanthosis,
      hyperkeratosis, acanthosis and epithelial dysplasia (p<0.05). Cell proliferation
      rate was different between different subtypes of non-dysplastic leukoplakias and
      this group presented a higher proliferative behavior when compared to normal oral
      epithelium. CONCLUSION: It may be suggested that non-dysplastic leukoplakias had
      different characteristics regarding cell proliferation rates and sometimes showed
      a proliferative behavior similar to that found in epithelial dysplasia. More
      studies should be conduced to increase knowledge about the biological profile of
      non-dysplastic leukoplakias, especially as it pertains to acanthosis.

PMID- 19767705
TI  - Tooth-implant connection: a bibliographic review.
AB  - The aim of this study was to carry out a bibliographic review of all available
      literature addressing the issue of whether or not the connection of teeth to
      implants by means of a prosthesis is a viable treatment alternative. Twenty
      articles from a variety of sources were analyzed and classified in order to draw
      conclusions. Articles were classified by type and an analysis was made of the
      different variables considered in each study, obtaining percentages of implant
      survival ranging from 84.4% to 100%, prosthetic complications ranging from 80% to
      90%, and the incidence of dental intrusion ranging from 0 to 5.6%. Biomechanical
      studies: Some articles studied models in order to assess different connections
      subjected to force, in which varying results were obtained. Rigid connections
      appeared to produce the most stress to the natural tooth, periodontal ligament
      and peri-implant bone; non-rigid connections reduced the stress to the bone, but
      increased stress to the prosthesis. CLINICAL STUDIES: The results obtained were
      disparate. Studies in the medium or short-term show this as a viable treatment
      alternative, whereas some studies point to a greater risk of complications,
      although the use of rigid connection decreases the percentage of intrusion. Other
      bibliographic reviews have concluded that there is a need for more longitudinal
      studies on the viability of tooth-implant connection, also concluding that
      complications are greater when this is the chosen treatment. As a viable
      alternative with an acceptable success rate, this course of treatment is always
      associated with rigid connection rather than non-rigid connection. Although
      intrusion is avoided with rigid connection, this nevertheless remains inadvisable
      as the primary treatment choice.

PMID- 19767706
TI  - Maxillary sinus septa: a systematic review.
AB  - This review analyzes articles published on the presence of septa in maxillary
      sinuses. An automated search was conducted on PubMed using different key words.
      This search resulted in 11 papers in which the presence of antral septa was
      assessed. These septa are barriers of cortical bone that arise from the floor or
      from the walls of the sinus and may even divide the sinus into two or more
      cavities. They may originate during maxillary development and tooth growth, in
      which case they are known as primary septa; or they may be acquired structures
      resulting from the pneumatization of maxillary sinus after tooth loss, in which
      case they are called secondary septa. Several methods have been used in their
      study, direct observation on dried skulls or during sinus lift procedures; and
      radiographic observation using panoramic radiographs or computed tomographs.
      Between 13 and 35.3% of maxillary sinuses have septa. They can be located in any
      region of the maxillary sinus and their size can vary between 2.5 and 12.7 mm in
      mean length. Some authors have reported a higher prevalence of septa in atrophic
      edentulous areas than in non-atrophic ones. If a sinus lift is conducted in the
      presence of maxillary sinus septa, it may be necessary to modify the design of
      the lateral window in order to avoid fracturing the septa.

PMID- 19767707
TI  - Dental implants in patients treated with oral bisphosphonates: a bibliographic
      review.
AB  - Bisphosphonates inhibit bone resorption and are used to treat a range of
      pathologies, including Paget disease, osteoporosis, multiple myeloma and
      metastases associated with breast or prostate cancer. At present, there is no
      effective treatment for bisphosphonate induced osteonecrosis, so prevention is
      extremely important. Since quality of life deteriorates for those suffering
      osteonecrosis, maximum precautions should be taken with patients at risk, and
      especially whenever oral surgery, including dental implant placement, is
      contemplated. Dentists and oral or maxillofacial surgeons must keep up to date
      with the latest approaches to prevention, particularly when treating patients who
      are presently taking, or who will be taking bisphosphonates and are also
      candidates for dental implants.

PMID- 19767708
TI  - Relationship between preoperative anxiety and postoperative satisfaction in
      dental implant surgery with intravenous conscious sedation.
AB  - PURPOSE: To study if patient preoperative anxiety is related to age and gender
      and to compare preoperative anxiety with postoperative patient and surgeon
      satisfaction in dental implant surgery under intravenous conscious sedation.
      MATERIALS AND METHODS: Dental implants were placed in 102 patients under local
      anesthesia and intravenous conscious sedation. The procedures were performed with
      or without dental extractions, and with or without bone regeneration. Anxiety was
      evaluated using Corah's Dental Anxiety Scale and levels of surgeon and patient
      satisfaction were evaluated on an adapted scale. RESULTS: Low preoperative
      anxiety was observed in 27.8% of patients, moderate in 50%, and high in 22.2%.
      Mean value of anxiety was 9.8+/-3.7. The level of surgeon satisfaction was
      adequate in 87.8% of the surgeries; patients were awake and nervous in 4.4% of
      surgeries, and excessively sleepy, with little cooperation in 7.8% of surgeries.
      Regarding patient satisfaction, the procedure was comfortable for 23.3% of
      patients, neither comfortable nor uncomfortable for 28.9%, a slightly
      uncomfortable experience for 36.7%, and very uncomfortable for 10% of patients.
      Younger patients and women were observed to have more anxiety, the difference
      being statistically significant. Patients with higher preoperative anxiety
      expressed a lower level of satisfaction, with statistically significant
      differences. There was no significant relationship between preoperative patient
      anxiety and postoperative surgeon satisfaction. CONCLUSION: Anxiety was higher in
      younger patients and women. In this study, a higher preoperative patient anxiety
      was associated with lower patient satisfaction, but had no influence on
      postoperative surgeon satisfaction.

PMID- 19767709
TI  - The implant-supported milled bar overdenture: a literature review.
AB  - PURPOSE: This bibliographical review aims to determine the present situation of
      the implant-supported milled bar overdenture as a therapeutic option in
      implantology, as well as to set and compare the techniques and materials
      currently used for making them. MATERIALS AND METHODS: By searching the main
      electronic bibliographical data in indexed Medline articles, we obtained a total
      number of 20 articles that fulfilled the requirements of this bibliographical
      review. RESULTS: The implant-supported milled bar overdenture offers excellent
      long-term successful results, although complication rates are higher in emergency
      cases of patients initially planned for a fixed prosthesis. Krenmair and
      collaborators found cumulative survival rates of implants on milled bars after 5
      years, of 99% in mandible cases, and of 97.8% in maxilla cases. No detailed
      protocols specifying the necessary number of implants or their characteristics
      have been found, though they are never made with less than 4 implants in mandible
      or 4-6 in the maxilla. Milled bars are screwed, generally cast in a precious
      metal alloy, with a metal or acrylic suprastructure and include attachments that
      regulate the tightness. The suprastructure adjusts precisely and rigidly to the
      milled bar, and presents similar biomechanical movements to those of fixed
      prostheses. The overdenture is removable and its prophylaxis is simple.
      CONCLUSIONS: The implant supported milled bar overdenture is a very interesting
      option in the treatment of patients with moderate to severe reabsorbed maxilla
      problems. It offers both the advantages of removable prostheses as well as the
      stability and retention of a fixed prosthesis.

PMID- 19767710
TI  - Electromyographic study of activity of the masseter and anterior temporalis
      muscles in patients with temporomandibular joint (TMJ) dysfunction: comparison
      with the clinical dysfunction index.
AB  - OBJECTIVES: A comparison was made between the electromyographic patterns specific
      to patient with temporomandibular disorders and that of normal healthy patients.
      STUDY DESIGN: Electromyographic tests were carried out during rest and function
      of the masseter muscles and anterior temporalis muscles in a homogeneous group
      consisting of 95 patients for whom such pathology and its different degree of
      severity had been previously studied by means of a Helkimo Test. The
      electromyographic exploration results were compared to those of a control group
      consisting of 31 healthy subjects. RESULTS: There were significant differences
      among patients with a different degree of clinical dysfunction, as well as
      between these and the control group. These differences were more important during
      maximum effort clenching and mastication. During maximum effort clenching,
      differences in masseteric activity were observed between control group and group
      III, between groups I and II and between groups I and III. Meanwhile, differences
      in temporalis activity were significant among all groups except between groups I
      and II. The multiple comparison analysis demonstrated the existence of
      significant statistical differences between healthy subjects and patients with
      severe TMD. However, the linear combination of these electromyographic (EMG)
      variables led us to elaborate four linear functions that classify all subjects
      into four well defined groups. Once extreme cases were eliminated, our EMG
      classification revealed an 80% match with that of the Helkimo Test. We thus
      conclude that in many cases, classification using electromyographic criteria
      matches that established by the Helkimo Test.

PMID- 19767711
TI  - The evaluation of psychiatric drug therapy on oral lichen planus patients with
      psychiatric disorders.
AB  - OBJECTIVES: Current treatments of oral lichen planus are palliative, not
      curative. Because psychiatric disorders significantly influence the development
      and severity of oral lichen planus, the use of psychiatric drug therapy may be an
      adjunct in treatment. The purpose of this study was to determine the efficacy of
      drug therapy of psychiatric disorders in oral lichen planus. STUDY DESIGN: Our
      controlled clinical study consisted of forty-six patients with oral lichen planus
      and psychiatric disorders who were randomly divided into two groups. Both groups
      were given topical corticosteroids and the study group received additional
      psychiatric drug therapy. Patients were monitored for a period of 6 months.
      Response to treatment was evaluated in each group and was compared with the other
      group using Mann-Whitney tests. We evaluated the correlation between psychiatric
      disorders and the recovery of oral lesions using Spearman's correlation
      coefficient analysis. RESULTS: Decrease in the size of the lesions was
      significantly greater in the study group after six months, but this difference
      was not significant in relationship to the pain experienced and the kind of
      lesion. Spearman's correlation coefficient analysis demonstrated that, in the
      sixth month, there was a significant and direct relationship between recovery
      from the psychiatric disorders and response to treatment of OLP lesions,
      particularly as it pertained to the kind of lesion. CONCLUSION: The present study
      indicates that the combination of psychiatric drug therapy and routine treatment
      methods were effective in reducing the size of the lesions, but did not have any
      significant effect on the symptoms.

PMID- 19767712
TI  - Periodontal disease and oral hygiene benefits in HIV seropositive and AIDS
      patients.
AB  - OBJECTIVES: The frequency of gingival and periodontal disease in HIV-seropositive
      and AIDS patients was investigated in order to evaluate the oral hygiene benefits
      of using mechanical therapy. STUDY DESIGN: thirty-two consenting HIV-positive
      patients were examined. Their gingival and periodontal status were evaluated
      using the Gingival Index and the Simplified Oral Hygiene Index. The data were
      assessed at baseline, after three months and after six months. Subjects received
      mechanical therapy, which included calculus removal, scaling and root planning,
      tooth polishing and oral hygiene instructions. The maintenance of oral hygiene
      was performed weekly. HIV staging and CD4 counts were also investigated. RESULTS:
      At the baseline, gingival and periodontal disease was present in 71.9% of all
      subjects. Chronic gingivitis (43.8%) was the most frequent in all subjects. A
      clear improvement in gingival health was registered in 78.2% of subjects after
      six months of mechanical therapy. No association was registered between CD4 count
      and gingival/periodontal status or attachment loss with HIV staging. CONCLUSIONS:
      Chronic gingivitis was the most frequent disease in HIV infected and AIDS
      patients. Oral hygiene using mechanical therapy improves the gingival condition,
      suggesting that it is an important step in the maintenance of periodontal health.

PMID- 19767713
TI  - Determinants of dental care utilization by the adult population in Buenos Aires.
AB  - OBJECTIVE: To establish the frequency with which the general population is seen
      by a dentist and the variables associated with the lack of regular dental check
      ups. METHODS: A cross-sectional study with a descriptive and analytical phase
      conducted in an urban community in Argentina. A sample population was obtained by
      stratified method. Socioeconomic conditions (measure by UBN index), health,
      health coverage, level of education and location of the households with respect
      to the dental clinics were all taken into consideration in selecting the sample.
      We performed a uni-and multivariate analysis. The statistical software used was
      SPSS 9.0 for Windows and EpiInfo6 Version 6.0. RESULTS: We observed significant
      associations between the lack of dental care and poverty levels, presence of UBN,
      living in the suburbs or at a remote distance from dental clinics, and the lack
      of health insurance. However, in a multiple regression analysis, only the
      geographical and socioeconomic characteristics of the respondents and their
      households had statistical significance. CONCLUSION: The section of the community
      that is less likely to visit their dentist regularly are those with higher socio
      economic risk. Having health insurance or having a dental clinic close to home
      does not ensure more frequent check-ups. Given that, as demonstrated in this
      work, spontaneous demand for attention is extremely low, public policies should
      aim to include this vulnerable population in preventive and scheduled care.

PMID- 19767714
TI  - Maxillary sinus lift performed using ultrasound. Evaluation of 21 patients.
AB  - PURPOSE: The aim of the present study was to evaluate the sinus membrane
      perforations that occurred during a sinus lift procedure using the ultrasound
      technique, and to evaluate the bone gain obtained. MATERIALS AND METHODS: In 21
      patients, 26 sinus lifts were performed using ultrasound and filled with bone
      graft material. The bone height and the bone gain obtained were observed in
      postoperative orthopantomographs, correcting for previous distortion. RESULTS: Of
      the 26 maxillary sinus lifts, 4 Schneiderian membrane perforations were observed.
      The average bone height prior to the intervention was 3.5 mm (scale 0.6- 8.7 mm )
      and the average postsurgical bone height was 10.8 mm (scale 7.5- 15.6 mm). An
      average bone gain of 7.2 mm was observed (range 2.5- 11.7 mm). CONCLUSIONS: Based
      on the results of this study, during ultrasound sinus lift, few Schneiderian
      membrane perforations occurred and all were small .

PMID- 19767715
TI  - Autogenous calvarium bone grafting as a treatment for severe bone resorption in
      the upper maxilla: a case report.
AB  - Atrophic maxilla rehabilitation has been the subject of several studies for
      decades; despite this, there are still many different therapeutic choices for the
      best way to treat maxillary resorption in order to enable implant placement and
      integration. These possibilities include the optimal use of remaining bone
      structures, such as the pterygoid processes or zygomatic arch, which involves
      using zygomaticus and pterygoid implants in combination with standard implants
      placed in the residual bone; alternatively, regenerative techniques, alveolar
      bone expansion/distraction or bone grafting techniques may be used. Severe
      maxillary atrophy has a multifactorial aetiology; the most important factors
      being long evolution edentulism, hyperpneumatization of the maxillary sinus, post
      traumatic deficit, bone loss after surgery (tumours, cysts) and periodontal
      problems or infection. In this report, we present a clinical case of onlay block
      reconstruction in an atrophic maxilla with harvested cranial calvarium bone
      grafts for successful future implant-supported oral rehabilitation.

PMID- 19767716
TI  - Current status of the torus palatinus and torus mandibularis.
AB  - While there is a hereditary component to tori, this does not explain all cases.
      Tori tend to appear more frequently during middle age of life; the torus
      palatinus is more commonly observed in females, but this is not the case with the
      torus mandibularis. Certain ethnic groups are more prone to one torus or the
      other. The torus is mainly removed due to prostodontic reasons, as it may also be
      used as biomaterial, not only in periodontology, but also in implantology. The
      aim of this study was a review of the literature from the past twenty years.

PMID- 19767717
TI  - DNA extraction from 0.22 microM Sterivex filters and cesium chloride density
      gradient centrifugation.
AB  - This method is used to extract high molecular weight genomic DNA from planktonic
      biomass concentrated on 0.22 microM Sterivex filters that have been treated with
      storage/lysis buffer and archived at -80 degrees C, and to purify this DNA using
      a cesium chloride density gradient. The protocol begins with two one-hour
      incubation steps to liberate DNA from cells and remove RNA. Next, a series of
      Phenol:Chloroform and Chloroform extractions are performed followed by
      centrifugation to remove proteins and cell membrane components, collection of the
      aqueous DNA extract, and several buffer exchange steps to wash and concentrate
      the extract. Part Five describes the optional purification via cesium chloride
      density gradient. It is recommended to work with less than 15 samples at one time
      to avoid confusion and cut down protocol time. The total time required for this
      protocol depends on the number of samples to be extracted. For 10-15 samples and
      assuming the proper centrifugation equipment is available, this entire protocol
      should take 3 days. Make sure you have the hybridization ovens set to temperature
      at the outset of the process.

PMID- 19767718
TI  - A long way to go...
AB  - Federal policy on human embryonic stem cell research must become bolder to truly
      support progress in the field.

PMID- 19767719
TI  - Knighting immunology.

PMID- 19767720
TI  - Renaissance for mouse models of human hematopoiesis and immunobiology.
AB  - More than 20 years after the first successful engraftment of human leukocytes and
      hematopoietic organs in mice, scientists met for the 2nd International Workshop
      on Humanized Mice to discuss progress and to highlight expectations in this
      dynamic field.

PMID- 19767721
TI  - The immune system as an invisible, silent Grand Fugue. Interview by Luke O'Neill.
AB  - The Science Gallery, Trinity College Dublin, recently held an exhibition called
      "INFECTIOUS: STAY AWAY" that used art to illustrate infection and immunity. Luke
      O'Neill talks to one of the artists, Gordana Novakovic, about her involvement in
      this project.

PMID- 19767722
TI  - The importance of being earnestly selfish.

PMID- 19767723
TI  - New DNA-sensing pathway feeds RIG-I with RNA.

PMID- 19767724
TI  - A defining factor for natural killer cell development.

PMID- 19767725
TI  - Beyond peptidoglycan for Nod2.

PMID- 19767727
TI  - Immunomodulator agent-related lymphoproliferative disorders.
AB  - The recent development of inhibitors of key immune response proteins has
      revolutionized the therapy of autoimmune diseases; these immunomodulator agents
      include monoclonal antibodies and receptor antagonists. However, as with all
      therapies, these new agents are not without side effects and complications. In
      particular, anti-tumor necrosis factor alpha (TNFalpha) agents have been reported
      to be associated with an increased incidence of lymphoproliferative disorders,
      infections, and vasculitis. We evaluated the clinicopathological features of 18
      cases of immunomodulator agent-related lymphoproliferative disorders (IAR-LPD)
      from several institutions. These included 6 cases of B-cell lymphoma, 2 cases of
      T-cell lymphoma, 3 cases of classical Hodgkin lymphoma, and 7 atypical lymphoid
      proliferations that did not fulfill diagnostic criteria for lymphoma; two of the
      latter regressed after discontinuation of the immunomodulator agent therapy. All
      eight lymphoma patients with available information had also received prior
      chemotherapy (methotrexate or 6-mercaptopurine). EBV was strongly associated with
      the B-cell and classical Hodgkin lymphomas. This case series illustrates that a
      broad range of lymphoid proliferations can occur after immunomodulator agent
      therapy and that these immunomodulator agent-related lymphoproliferative
      disorders have considerable overlap with other well-defined lymphoproliferative
      diseases associated with iatrogenic immunosuppression. Further study is warranted
      to evaluate how these therapies interact with other immunosuppressive agents and
      the underlying abnormal immune system to enhance the development of lymphomas and
      atypical lymphoid proliferations.

PMID- 19767728
TI  - Comparative analysis of annexin-1 in neuroepithelial tumors shows altered
      expression with the grade of malignancy but is not associated with survival.
AB  - In various types of cancer, the expression of members of the annexin family of
      calcium- and phospholipid-binding anti-inflammatory proteins is dysregulated.
      Annexin-1 (ANXA1, lipocortin-1) is involved in proliferation, differentiation and
      apoptosis. It serves as a substrate for the epidermal growth factor receptor
      (EGFR), which is frequently amplified in primary gliomas. It is unclear how
      annexin-1 is expressed in various neuroepithelial tumors, and whether there is
      any association with tumor malignancy or survival. We studied annexin-1
      expression in 394 glial neoplasms of all grades of malignancy and 81 normal brain
      samples by immunohistochemistry using tissue microarrays. The results were
      validated using western blot and reverse transcription-PCR (RT-PCR). In the
      normal human brain, the expression of annexin-1 is limited to ependymal cells and
      subependymal astrocytes, but is also upregulated in reactive astrocytes.
      Ependymomas and astrocytomas showed significantly higher mean annexin-1
      expression levels in the cytoplasm compared with oligodendrogliomas (both:
      P<0.0001). In addition, nuclear staining of annexin-1 in oligodendroglial tumor
      cells was significantly reduced (P=0.0002), which may be used as a diagnostic
      tool for differentiating between astrocytomas and oligodendrogliomas. Although
      annexin-1 expression in ependymomas decreased with the grade of malignancy,
      diffuse astrocytomas showed a significant increase in cytoplasmic annexin-1
      positive tumor cells. However, survival analysis showed that the expression of
      annexin-1 is not associated with patient survival. Similar to the EGFR
      amplification profile, primary glioblastomas had a higher annexin-1 expression
      level compared with secondary glioblastomas. Thus, annexin-1 upregulation in
      astrocytomas may contribute to tumor progression and its expression profile is
      similar to its substrate, EGFR, suggesting a possible regulation thereof.

PMID- 19767729
TI  - Simultaneous detection of TOP2A and HER2 gene amplification by multiplex ligation
      dependent probe amplification in breast cancer.
AB  - HER-2/neu gene amplification, found in certain subtypes of (breast-) cancers, is
      an independent prognostic factor of poor outcome and determines eligibility for
      systemic treatment with trastuzumab. TopoII alpha (TOP2A) gene amplification
      seems to be predictive of response to a class of cytostatic agents called TopoII
      inhibitors, which include the anthracyclines. The observed increased efficacy of
      anthracyclines in HER2-positive tumors is thought to arise from the close
      proximity of both genes on chromosome 17, where the TopoII amplification status
      will determine the anthracycline sensitivity. This study aimed to validate a new
      polymerase chain reaction-based test, called multiplex ligation-dependent probe
      amplification (MLPA), as a simple and quick method to simultaneously assess HER
      2/neu and TopoII alpha gene amplification status in paraffin-embedded breast
      cancer samples. To this end, MLPA results were compared with TopoII alpha, HER2
      chromogenic in situ hybridization (CISH). We also assessed TopoII alpha protein
      expression by immunohistochemistry. Of 353 patients, 9% showed TopoII alpha
      amplification by MLPA and 13% of patients were HER2 amplified. TopoII alpha
      amplification was seen in 42% of HER2-amplified cases and showed no high level
      amplification without HER2 amplification. Eleven patients displayed TopoI alpha
      loss (3%). Concordance between MLPA and CISH was 91% for TopoII alpha and 96% for
      HER2. Correlation between amplification and overexpression of TopoII alpha was
      significant (P=0.035), but amplification did not always predict protein
      overexpression. Loss of the TopoII alpha gene was almost never associated with
      loss of its protein. In conclusion, MLPA is an easy and accurate method to
      simultaneously detect breast cancer HER-2/neu and TopoII alpha copy number status
      in paraffin-embedded tissue, and thus an attractive supplement or alternative to
      CISH.

PMID- 19767730
TI  - Role of the polycomb protein EED in the propagation of repressive histone marks.
AB  - Polycomb group proteins have an essential role in the epigenetic maintenance of
      repressive chromatin states. The gene-silencing activity of the Polycomb
      repressive complex 2 (PRC2) depends on its ability to trimethylate lysine 27 of
      histone H3 (H3K27) by the catalytic SET domain of the EZH2 subunit, and at least
      two other subunits of the complex: SUZ12 and EED. Here we show that the carboxy
      terminal domain of EED specifically binds to histone tails carrying trimethyl
      lysine residues associated with repressive chromatin marks, and that this leads
      to the allosteric activation of the methyltransferase activity of PRC2. Mutations
      in EED that prevent it from recognizing repressive trimethyl-lysine marks abolish
      the activation of PRC2 in vitro and, in Drosophila, reduce global methylation and
      disrupt development. These findings suggest a model for the propagation of the
      H3K27me3 mark that accounts for the maintenance of repressive chromatin domains
      and for the transmission of a histone modification from mother to daughter cells.

PMID- 19767731
TI  - A proteomics approach to discovering natural products and their biosynthetic
      pathways.
AB  - Many natural products with antibiotic, anticancer and antifungal properties are
      synthesized by nonribosomal peptide synthetases (NRPSs) and polyketide synthases
      (PKSs). Although genome sequencing has revealed the diversity of these enzymes,
      identifying new products and their biosynthetic pathways remains challenging. By
      taking advantage of the size of these enzymes (often >2,000 amino acids) and
      unique marker ions derived from their common phosphopantetheinyl cofactor, we
      adapted mass spectrometry-based proteomics to selectively detect NRPS and PKS
      gene clusters in microbial proteomes without requiring genome sequence
      information. We detected known NRPS systems in members of the genera Bacillus and
      Streptomyces, and screened 22 environmental isolates to uncover production of
      unknown natural products from the hybrid NRPS-PKS zwittermicin A biosynthetic
      gene cluster. We also discovered an NRPS cluster that generates a seven-residue
      lipopeptide. This 'protein-first' strategy complements bioassay- and sequence
      based approaches by finding expressed gene clusters that produce new natural
      products.

PMID- 19767732
TI  - Activation of the NLRP3 inflammasome in dendritic cells induces IL-1beta
      dependent adaptive immunity against tumors.
AB  - The therapeutic efficacy of anticancer chemotherapies may depend on dendritic
      cells (DCs), which present antigens from dying cancer cells to prime tumor
      specific interferon-gamma (IFN-gamma)-producing T lymphocytes. Here we show that
      dying tumor cells release ATP, which then acts on P2X(7) purinergic receptors
      from DCs and triggers the NOD-like receptor family, pyrin domain containing-3
      protein (NLRP3)-dependent caspase-1 activation complex ('inflammasome'), allowing
      for the secretion of interleukin-1beta (IL-1beta). The priming of IFN-gamma
      producing CD8+ T cells by dying tumor cells fails in the absence of a functional
      IL-1 receptor 1 and in Nlpr3-deficient (Nlrp3(-/-)) or caspase-1-deficient (Casp
      1(-/-)) mice unless exogenous IL-1beta is provided. Accordingly, anticancer
      chemotherapy turned out to be inefficient against tumors established in
      purinergic receptor P2rx7(-/-) or Nlrp3(-/-) or Casp1(-/-) hosts. Anthracycline
      treated individuals with breast cancer carrying a loss-of-function allele of
      P2RX7 developed metastatic disease more rapidly than individuals bearing the
      normal allele. These results indicate that the NLRP3 inflammasome links the
      innate and adaptive immune responses against dying tumor cells.

PMID- 19767733
TI  - Kcne2 deletion uncovers its crucial role in thyroid hormone biosynthesis.
AB  - Thyroid dysfunction is a global health concern, causing defects including
      neurodevelopmental disorders, dwarfism and cardiac arrhythmia. Here, we show that
      the potassium channel subunits KCNQ1 and KCNE2 form a thyroid-stimulating hormone
      stimulated, constitutively active, thyrocyte K+ channel required for normal
      thyroid hormone biosynthesis. Targeted disruption of Kcne2 in mice impaired
      thyroid iodide accumulation up to eightfold, impaired maternal milk ejection,
      halved milk tetraiodothyronine (T4) content and halved litter size. Kcne2
      deficient mice had hypothyroidism, dwarfism, alopecia, goiter and cardiac
      abnormalities including hypertrophy, fibrosis, and reduced fractional shortening.
      The alopecia, dwarfism and cardiac abnormalities were alleviated by
      triiodothyronine (T3) and T4 administration to pups, by supplementing dams with
      T(4) before and after they gave birth or by feeding the pups exclusively from
      Kcne2+/+ dams; conversely, these symptoms were elicited in Kcne2+/+ pups by
      feeding exclusively from Kcne2-/- dams. These data provide a new potential
      therapeutic target for thyroid disorders and raise the possibility of an
      endocrine component to previously identified KCNE2- and KCNQ1-linked human
      cardiac arrhythmias.

PMID- 19767734
TI  - The obesity susceptibility gene Cpe links FoxO1 signaling in hypothalamic pro
      opiomelanocortin neurons with regulation of food intake.
AB  - Reduced food intake brings about an adaptive decrease in energy expenditure that
      contributes to the recidivism of obesity after weight loss. Insulin and leptin
      inhibit food intake through actions in the central nervous system that are partly
      mediated by the transcription factor FoxO1. We show that FoxO1 ablation in pro
      opiomelanocortin (Pomc)-expressing neurons in mice (here called Pomc-Foxo1(-/-)
      mice) increases Carboxypeptidase E (Cpe) expression, resulting in selective
      increases of alpha-melanocyte-stimulating hormone (alpha-Msh) and carboxy-cleaved
      beta-endorphin, the products of Cpe-dependent processing of Pomc. This
      neuropeptide profile is associated with decreased food intake and normal energy
      expenditure in Pomc-Foxo1(-/-) mice. We show that Cpe expression is downregulated
      by diet-induced obesity and that FoxO1 deletion offsets the decrease, protecting
      against weight gain. Moreover, moderate Cpe overexpression in the arcuate nucleus
      phenocopies features of the FoxO1 mutation. The dissociation of food intake from
      energy expenditure in Pomc-Foxo1(-/-) mice represents a model for therapeutic
      intervention in obesity and raises the possibility of targeting Cpe to develop
      weight loss medications.

PMID- 19767735
TI  - The yeast Wsc1 cell surface sensor behaves like a nanospring in vivo.
AB  - Here we report on in vivo measurement of the mechanical behavior of a cell
      surface sensor using single-molecule atomic force microscopy. We focus on the
      yeast wall stress component sensor Wsc1, a plasma membrane protein that is
      thought to function as a rigid probe of the cell wall status. We first map the
      distribution of individual histidine-tagged sensors on living yeast cells by
      scanning the cell surface with atomic force microscopy tips carrying
      nitrilotriacetate groups. We then show that Wsc1 behaves like a linear nanospring
      that is capable of resisting high mechanical force and of responding to cell
      surface stress. Both a genomic pmt4 deletion and the insertion of a stretch of
      glycines in Wsc1 result in substantial alterations in protein spring properties,
      supporting the important role of glycosylation at the extracellular
      serine/threonine-rich region.

PMID- 19767736
TI  - Conformational inhibition of the hepatitis C virus internal ribosome entry site
      RNA.
AB  - The internal ribosome entry site (IRES), a highly conserved structured element of
      the hepatitis C virus (HCV) genomic RNA, is an attractive target for antiviral
      drugs. Here we show that benzimidazole inhibitors of the HCV replicon act by
      conformational induction of a widened interhelical angle in the IRES subdomain
      IIa, which facilitates the undocking of subdomain IIb from the ribosome and
      ultimately leads to inhibition of IRES-driven translation in HCV-infected cells.

PMID- 19767737
TI  - Imaging single atoms using secondary electrons with an aberration-corrected
      electron microscope.
AB  - Aberration correction has embarked on a new frontier in electron microscopy by
      overcoming the limitations of conventional round lenses, providing sub-angstrom
      sized probes. However, improvement of spatial resolution using aberration
      correction so far has been limited to the use of transmitted electrons both in
      scanning and stationary mode, with an improvement of 20-40% (refs 3-8). In
      contrast, advances in the spatial resolution of scanning electron microscopes
      (SEMs), which are by far the most widely used instrument for surface imaging at
      the micrometre-nanometre scale, have been stagnant, despite several recent
      efforts. Here, we report a new SEM, with aberration correction, able to image
      single atoms by detecting electrons emerging from its surface as a result of
      interaction with the small probe. The spatial resolution achieved represents a
      fourfold improvement over the best-reported resolution in any SEM (refs 10-12).
      Furthermore, we can simultaneously probe the sample through its entire thickness
      with transmitted electrons. This ability is significant because it permits the
      selective visualization of bulk atoms and surface ones, beyond a traditional two
      dimensional projection in transmission electron microscopy. It has the potential
      to revolutionize the field of microscopy and imaging, thereby opening the door to
      a wide range of applications, especially when combined with simultaneous
      nanoprobe spectroscopy.

PMID- 19767738
TI  - Linking catalyst composition to chirality distributions of as-grown single-walled
      carbon nanotubes by tuning Ni(x)Fe(1-x) nanoparticles.
AB  - Chirally pure single-walled carbon nanotubes (SWCNTs) are required for various
      applications ranging from nanoelectronics to nanomedicine. Although significant
      efforts have been directed towards separation of SWCNT mixtures, including
      density-gradient ultracentrifugation , chromatography and electrophoresis, the
      initial chirality distribution is determined during growth and must be controlled
      for non-destructive, scalable and economical production. Here, we show that the
      chirality distribution of as-grown SWCNTs can be altered by varying the
      composition of Ni(x)Fe(1-x) nanocatalysts. Precise tuning of the nanocatalyst
      composition at constant size is achieved by a new gas-phase synthesis route based
      on an atmospheric-pressure microplasma. The link between the composition
      dependent crystal structure of the nanocatalysts and the resulting nanotube
      chirality supports epitaxial models and is a step towards chiral-selective growth
      of SWCNTs.

PMID- 19767739
TI  - Morphology-dependent zeolite intergrowth structures leading to distinct internal
      and outer-surface molecular diffusion barriers.
AB  - Zeolites play a crucial part in acid-base heterogeneous catalysis. Fundamental
      insight into their internal architecture is of great importance for understanding
      their structure-function relationships. Here, we report on a new approach
      correlating confocal fluorescence microscopy with focused ion beam-electron
      backscatter diffraction, transmission electron microscopy lamelling and
      diffraction, atomic force microscopy and X-ray photoelectron spectroscopy to
      study a wide range of coffin-shaped MFI-type zeolite crystals differing in their
      morphology and chemical composition. This powerful combination demonstrates a
      unified view on the morphology-dependent MFI-type intergrowth structures and
      provides evidence for the presence and nature of internal and outer-surface
      barriers for molecular diffusion. It has been found that internal-surface
      barriers originate not only from a 90 degrees mismatch in structure and pore
      alignment but also from small angle differences of 0.5 degrees-2 degrees for
      particular crystal morphologies. Furthermore, outer-surface barriers seem to be
      composed of a silicalite outer crust with a thickness varying from 10 to 200 nm.

PMID- 19767740
TI  - The planar cell polarity effector Fuz is essential for targeted membrane
      trafficking, ciliogenesis and mouse embryonic development.
AB  - The planar cell polarity (PCP) signalling pathway is essential for embryonic
      development because it governs diverse cellular behaviours, and 'core PCP'
      proteins, such as Dishevelled and Frizzled, have been extensively characterized.
      By contrast, the 'PCP effector' proteins, such as Intu and Fuz, remain largely
      unstudied. These proteins are essential for PCP signalling, but they have never
      been investigated in mammals and their cell biological activities remain entirely
      unknown. We report here that Fuz mutant mice show neural tube defects, skeletal
      dysmorphologies and Hedgehog signalling defects stemming from disrupted
      ciliogenesis. Using bioinformatics and imaging of an in vivo mucociliary
      epithelium, we established a central role for Fuz in membrane trafficking,
      showing that Fuz is essential for trafficking of cargo to basal bodies and to the
      apical tips of cilia. Fuz is also essential for exocytosis in secretory cells.
      Finally, we identified a Rab-related small GTPase as a Fuz interaction partner
      that is also essential for ciliogenesis and secretion. These results are
      significant because they provide new insights into the mechanisms by which
      developmental regulatory systems such as PCP signalling interface with
      fundamental cellular systems such as the vesicle trafficking machinery.

PMID- 19767741
TI  - Intracellular fluid flow in rapidly moving cells.
AB  - Cytosolic fluid dynamics have been implicated in cell motility because of the
      hydrodynamic forces they induce and because of their influence on transport of
      components of the actin machinery to the leading edge. To investigate the
      existence and the direction of fluid flow in rapidly moving cells, we introduced
      inert quantum dots into the lamellipodia of fish epithelial keratocytes and
      analysed their distribution and motion. Our results indicate that fluid flow is
      directed from the cell body towards the leading edge in the cell frame of
      reference, at about 40% of cell speed. We propose that this forward-directed flow
      is driven by increased hydrostatic pressure generated at the rear of the cell by
      myosin contraction, and show that inhibition of myosin II activity by
      blebbistatin reverses the direction of fluid flow and leads to a decrease in
      keratocyte speed. We present a physical model for fluid pressure and flow in
      moving cells that quantitatively accounts for our experimental data.

PMID- 19767742
TI  - The bacterial virulence factor InlC perturbs apical cell junctions and promotes
      cell-to-cell spread of Listeria.
AB  - Several pathogenic bacteria, including Listeria monocytogenes, use an F-actin
      motility process to spread between mammalian cells. Actin 'comet tails' propel
      Listeria through the cytoplasm, resulting in bacteria-containing membrane
      protrusions that are internalized by neighbouring cells. The mechanism by which
      Listeria overcomes cortical tension to generate protrusions is unknown. Here, we
      identify bacterial and host proteins that directly regulate protrusions. We show
      that efficient spreading between polarized epithelial cells requires the secreted
      Listeria virulence protein InlC (internalin C). We next identify the mammalian
      adaptor protein Tuba as a ligand of InlC. InlC binds to a carboxy-terminal SH3
      domain in Tuba, which normally engages the human actin regulatory protein N-WASP.
      InlC promotes protrusion formation by inhibiting Tuba and N-WASP activity,
      probably by impairing binding of N-WASP to the Tuba SH3 domain. Tuba and N-WASP
      are known to control the structure of apical junctions in epithelial cells. We
      demonstrate that, by inhibiting Tuba and N-WASP, InlC makes taut apical junctions
      become slack. Experiments with myosin II inhibitors indicate that InlC-mediated
      perturbation of apical junctions accounts for the role of this bacterial protein
      in protrusion formation. Collectively, our results suggest that InlC promotes
      bacterial dissemination by relieving cortical tension, thereby enhancing the
      ability of motile bacteria to deform the plasma membrane into protrusions.

PMID- 19767743
TI  - Signalling mediated by the endoplasmic reticulum stress transducer OASIS is
      involved in bone formation.
AB  - Eukaryotic cells have signalling pathways from the endoplasmic reticulum (ER) to
      cytosol and nuclei, to avoid excess accumulation of unfolded proteins in the ER.
      We previously identified a new type of ER stress transducer, OASIS, a bZIP (basic
      leucine zipper) transcription factor, which is a member of the CREB/ATF family
      and has a transmembrane domain. OASIS is processed by regulated intramembrane
      proteolysis (RIP) in response to ER stress, and is highly expressed in
      osteoblasts. OASIS(-/-) mice exhibited severe osteopenia, involving a decrease in
      type I collagen in the bone matrix and a decline in the activity of osteoblasts,
      which showed abnormally expanded rough ER, containing of a large amount of bone
      matrix proteins. Here we identify the gene for type 1 collagen, Col1a1, as a
      target of OASIS, and demonstrate that OASIS activates the transcription of Col1a1
      through an unfolded protein response element (UPRE)-like sequence in the
      osteoblast-specific Col1a1 promoter region. Moreover, expression of OASIS in
      osteoblasts is induced by BMP2 (bone morphogenetic protein 2), the signalling of
      which is required for bone formation. Additionally, RIP of OASIS is accelerated
      by BMP2 signalling, which causes mild ER stress. Our studies show that OASIS is
      critical for bone formation through the transcription of Col1a1 and the secretion
      of bone matrix proteins, and they reveal a new mechanism by which ER stress
      induced signalling mediates bone formation.

PMID- 19767744
TI  - Regulation of endoplasmic reticulum stress response by a BBF2H7-mediated Sec23a
      pathway is essential for chondrogenesis.
AB  - Many tissues have a specific signal transduction system for endoplasmic reticulum
      (ER) dysfunction; however, the mechanisms underlying the ER stress response in
      cartilage remain unclear. BBF2H7 (BBF2 human homologue on chromosome 7), an ER
      resident basic leucine zipper transcription factor, is activated in response to
      ER stress and is highly expressed in chondrocytes. In this study, we generated
      Bbf2h7(-/-) mice to assess the in vivo function of BBF2H7. The mice showed severe
      chondrodysplasia and died by suffocation shortly after birth because of an
      immature chest cavity. The cartilage showed a lack of typical columnar structure
      in the proliferating zone and a decrease in the size of the hypertrophic zone,
      resulting in a significant reduction of extracellular matrix proteins.
      Interestingly, proliferating chondrocytes showed abnormally expanded ER,
      containing aggregated type II collagen (Col2) and cartilage oligomeric matrix
      protein (COMP). We identified Sec23a, which encodes a coat protein complex II
      component responsible for protein transport from the ER to the Golgi, as a target
      of BBF2H7, which directly bound to a CRE-like sequence in the promoter region of
      Sec23a to activate its transcription. When Sec23a was introduced to Bbf2h7(-/-)
      chondrocytes, the impaired transport and secretion of cartilage matrix proteins
      was totally restored, indicating that by activating protein secretion the BBF2H7
      Sec23a pathway has a crucial role in chondrogenesis. Our findings provide a new
      link by which ER stress is converted to signalling for the activation of ER-to
      Golgi trafficking.

PMID- 19767745
TI  - MyosinV controls PTEN function and neuronal cell size.
AB  - The tumour suppressor PTEN can inhibit cell proliferation and migration as well
      as control cell growth, in different cell types. PTEN functions predominately as
      a lipid phosphatase, converting PtdIns(3,4,5)P(3) to PtdIns(4,5)P(2), thereby
      antagonizing PI(3)K (phosphoinositide 3-kinase) and its established downstream
      effector pathways. However, much is unclear concerning the mechanisms that
      regulate PTEN movement to the cell membrane, which is necessary for its activity
      towards PtdIns(3,4,5)P(3) (Refs 3, 4, 5). Here we show a requirement for
      functional motor proteins in the control of PI3K signalling, involving a
      previously unknown association between PTEN and myosinV. FRET (Forster resonance
      energy transfer) measurements revealed that PTEN interacts directly with myosinV,
      which is dependent on PTEN phosphorylation mediated by CK2 and/or GSK3.
      Inactivation of myosinV-transport function in neurons increased cell size, which,
      in line with known attributes of PTEN-loss, required PI(3)K and mTor. Our data
      demonstrate a myosin-based transport mechanism that regulates PTEN function,
      providing new insights into the signalling networks regulating cell growth.

PMID- 19767746
TI  - Classical conditioning in the vegetative and minimally conscious state.
AB  - Pavlovian trace conditioning depends on the temporal gap between the conditioned
      and unconditioned stimuli. It requires, in mammals, functional medial temporal
      lobe structures and, in humans, explicit knowledge of the temporal contingency.
      It is therefore considered to be a plausible objective test to assess awareness
      without relying on explicit reports. We found that individuals with disorders of
      consciousness (DOCs), despite being unable to report awareness explicitly, were
      able to learn this procedure. Learning was specific and showed an anticipatory
      electromyographic response to the aversive conditioning stimulus, which was
      substantially stronger than to the control stimulus and was augmented as the
      aversive stimulus approached. The amount of learning correlated with the degree
      of cortical atrophy and was a good indicator of recovery. None of these effects
      were observed in control subjects under the effect of anesthesia (propofol). Our
      results suggest that individuals with DOCs might have partially preserved
      conscious processing, which cannot be mediated by explicit reports and is not
      detected by behavioral assessment.

PMID- 19767747
TI  - Transformation of nonfunctional spinal circuits into functional states after the
      loss of brain input.
AB  - After complete spinal cord transections that removed all supraspinal inputs in
      adult rats, combinations of serotonergic agonists and epidural electrical
      stimulation were able to acutely transform spinal networks from nonfunctional to
      highly functional and adaptive states as early as 1 week after injury. Using
      kinematics, physiological and anatomical analyses, we found that these
      interventions could recruit specific populations of spinal circuits, refine their
      control via sensory input and functionally remodel these locomotor pathways when
      combined with training. The emergence of these new functional states enabled full
      weight-bearing treadmill locomotion in paralyzed rats that was almost
      indistinguishable from voluntary stepping. We propose that, in the absence of
      supraspinal input, spinal locomotion can emerge from a combination of central
      pattern-generating capability and the ability of these spinal circuits to use
      sensory afferent input to control stepping. These findings provide a strategy by
      which individuals with spinal cord injuries could regain substantial levels of
      motor control.

PMID- 19767748
TI  - Distinct promoter dynamics of the basal transcription factor TBP across the yeast
      genome.
AB  - Transcription regulation in eukaryotes involves rapid recruitment and proper
      assembly of transcription factors at gene promoters. To determine the dynamics of
      the transcription machinery on DNA, we used a differential chromatin
      immunoprecipitation procedure coupled to whole-genome microarray detection in
      Saccharomyces cerevisiae. We find that TATA-binding protein (TBP) turnover is low
      at RNA polymerase I (Pol I) promoters. Whereas RNA polymerase III (Pol III)
      promoters represent an intermediate case, TBP turnover is high at RNA polymerase
      II (Pol II) promoters. Within these promoters, the highest turnover correlates
      with binding of the Spt-Ada-Gcn5 acetyltransferase complex (SAGA) coactivator,
      Mot1p dependence and presence of a canonical TATA box. In contrast, slow turnover
      Pol II promoters depend on TFIID and on the gene-specific factor, Rap1p. Together
      this shows that TBP turnover is regulated by protein factors rather than DNA
      sequence and argues that TBP turnover is an important determinant in regulating
      gene expression.

PMID- 19767749
TI  - Structural and kinetic determinants of protease substrates.
AB  - Two fundamental questions with regard to proteolytic networks and pathways
      concern the structural repertoire and kinetic threshold that distinguish
      legitimate signaling substrates. We used N-terminal proteomics to address these
      issues by identifying cleavage sites within the Escherichia coli proteome that
      are driven by the apoptotic signaling protease caspase-3 and the bacterial
      protease glutamyl endopeptidase (GluC). Defying the dogma that proteases cleave
      primarily in natively unstructured loops, we found that both caspase-3 and GluC
      cleave in alpha-helices nearly as frequently as in extended loops. Notably,
      biochemical and kinetic characterization revealed that E. coli caspase-3
      substrates are greatly inferior to natural substrates, suggesting protease and
      substrate coevolution. Engineering an E. coli substrate to match natural
      catalytic rates defined a kinetic threshold that depicts a signaling event. This
      unique combination of proteomics, biochemistry, kinetics and substrate
      engineering reveals new insights into the structure-function relationship of
      protease targets and their validation from large-scale approaches.

PMID- 19767750
TI  - Active site remodeling switches HIV specificity of antiretroviral TRIMCyp.
AB  - TRIMCyps are primate antiretroviral proteins that potently inhibit HIV
      replication. Here we describe how rhesus macaque TRIMCyp (RhTC) has evolved to
      target and restrict HIV-2. We show that the ancestral cyclophilin A (CypA) domain
      of RhTC targets HIV-2 capsid with weak affinity, which is strongly increased in
      RhTC by two mutations (D66N and R69H) at the expense of HIV-1 binding. These
      mutations disrupt a constraining intramolecular interaction in CypA, triggering
      the complete restructuring (>16 A) of an active site loop. This new configuration
      discriminates between divergent HIV-1 and HIV-2 loop conformations mediated by
      capsid residue 88. Viral sensitivity to RhTC restriction can be conferred or
      abolished by mutating position 88. Furthermore, position 88 determines the
      susceptibility of naturally occurring HIV-1 sequences to restriction. Our results
      reveal the complex molecular, structural and thermodynamic changes that underlie
      the ongoing evolutionary race between virus and host.

PMID- 19767751
TI  - Phosphoproteomics reveals new ERK MAP kinase targets and links ERK to nucleoporin
      mediated nuclear transport.
AB  - Many extracellular signal-regulated kinase (ERK) mitogen-activated protein (MAP)
      kinase substrates have been identified, but the diversity of ERK-mediated
      processes suggests the existence of additional targets. Using a phosphoproteomic
      approach combining the steroid receptor fusion system, IMAC, 2D-DIGE and
      phosphomotif-specific antibodies, we detected 38 proteins showing reproducible
      phosphorylation changes between ERK-activated and ERK-inhibited samples,
      including 24 new candidate ERK targets. ERK directly phosphorylated at least 13
      proteins in vitro. Of these, Nup50 was verified as a bona fide ERK substrate.
      Notably, ERK phosphorylation of the FG repeat region of Nup50 reduced its
      affinity for importin-beta family proteins, importin-beta and transportin. Other
      FG nucleoporins showed a similar functional change after ERK-mediated
      phosphorylation. Nuclear migration of importin-beta and transportin was impaired
      in ERK-activated, digitonin-permeabilized cells, as a result of ERK
      phosphorylation of Nup50. Thus, we propose that ERK phosphorylates various
      nucleoporins to regulate nucleocytoplasmic transport.

PMID- 19767754
TI  - Genome-wide association and replication studies identify four variants associated
      with prostate cancer susceptibility.
AB  - We report a prostate cancer genome-wide association follow-on study. We
      discovered four variants associated with susceptibility to prostate cancer in
      several European populations: rs10934853[A] (OR = 1.12, P = 2.9 x 10(-10)) on
      3q21.3; two moderately correlated (r2 = 0.07) variants, rs16902094[G] (OR = 1.21,
      P = 6.2 x 10(-15)) and rs445114[T] (OR = 1.14, P = 4.7 x 10(-10)), on 8q24.21;
      and rs8102476[C] (OR = 1.12, P = 1.6 x 10(-11)) on 19q13.2. We also refined a
      previous association signal on 11q13 with the SNP rs11228565[A] (OR = 1.23, P =
      6.7 x 10(-12)). In a multivariate analysis using 22 prostate cancer risk variants
      typed in the Icelandic population, we estimated that carriers in the top 1.3% of
      the risk distribution are at a 2.5 times greater risk of developing the disease
      than members of the general population.

PMID- 19767755
TI  - Identification of a new prostate cancer susceptibility locus on chromosome 8q24.
AB  - We report a genome-wide association study in 10,286 cases and 9,135 controls of
      European ancestry in the Cancer Genetic Markers of Susceptibility (CGEMS)
      initiative. We identify a new association with prostate cancer risk on chromosome
      8q24 (rs620861, P = 1.3 x 10(-10), heterozygote OR = 1.17, 95% CI 1.10-1.24;
      homozygote OR = 1.33, 95% CI 1.21-1.45). This defines a new locus associated with
      prostate cancer susceptibility on 8q24.

PMID- 19767756
TI  - Runx-CBFbeta complexes control expression of the transcription factor Foxp3 in
      regulatory T cells.
AB  - The transcription factor Foxp3 has an indispensable role in establishing stable
      transcriptional and functional programs of regulatory T cells (T(reg) cells).
      Loss of Foxp3 expression in mature T(reg) cells results in a failure of
      suppressor function, yet the molecular mechanisms that ensure steady, heritable
      Foxp3 expression in the T(reg) cell lineage remain unknown. Using T(reg) cell
      specific gene targeting, we found that complexes of the transcription factors
      Runx and CBFbeta were required for maintenance of Foxp3 mRNA and protein
      expression in T(reg) cells. Consequently, mice lacking CBFbetab exclusively in
      the T(reg) cell lineage had a moderate lymphoproliferative syndrome. Thus, Runx
      CBFbeta complexes maintain stable high expression of Foxp3 and serve as an
      essential determinant of T(reg) cell lineage stability.

PMID- 19767752
TI  - Multiple loci on 8q24 associated with prostate cancer susceptibility.
AB  - Previous studies have identified multiple loci on 8q24 associated with prostate
      cancer risk. We performed a comprehensive analysis of SNP associations across
      8q24 by genotyping tag SNPs in 5,504 prostate cancer cases and 5,834 controls. We
      confirmed associations at three previously reported loci and identified
      additional loci in two other linkage disequilibrium blocks (rs1006908: per-allele
      OR = 0.87, P = 7.9 x 10(-8); rs620861: OR = 0.90, P = 4.8 x 10(-8)). Eight SNPs
      in five linkage disequilibrium blocks were independently associated with prostate
      cancer susceptibility.

PMID- 19767757
TI  - CARD9 facilitates microbe-elicited production of reactive oxygen species by
      regulating the LyGDI-Rac1 complex.
AB  - In response to invading microorganisms, macrophages engage in phagocytosis and
      rapidly release reactive oxygen species (ROS), which serve an important
      microbicidal function. However, how phagocytosis induces ROS production remains
      largely unknown. CARD9, a caspase-recruitment domain (CARD)-containing protein,
      is important for resistance to fungal and bacterial infection. The mechanism of
      CARD9-mediated bacterial clearance is still mostly unknown. Here we show that
      CARD9 is required for killing intracellular bacteria in macrophages. CARD9
      associated with the GDP-dissociation inhibitor LyGDI in phagosomes after
      bacterial and fungal infection and binding of CARD9 suppressed LyGDI-mediated
      inhibition of the GTPase Rac1, thereby leading to ROS production and bacterial
      killing in macrophages. Thus, our studies identify a key pathway that leads to
      microbe-elicited ROS production.

PMID- 19767758
TI  - Tn-seq: high-throughput parallel sequencing for fitness and genetic interaction
      studies in microorganisms.
AB  - Biological pathways are structured in complex networks of interacting genes.
      Solving the architecture of such networks may provide valuable information, such
      as how microorganisms cause disease. Here we present a method (Tn-seq) for
      accurately determining quantitative genetic interactions on a genome-wide scale
      in microorganisms. Tn-seq is based on the assembly of a saturated Mariner
      transposon insertion library. After library selection, changes in frequency of
      each insertion mutant are determined by sequencing the flanking regions en masse.
      These changes are used to calculate each mutant's fitness. Using this approach,
      we determined fitness for each gene of Streptococcus pneumoniae, a causative
      agent of pneumonia and meningitis. A genome-wide screen for genetic interactions
      of five query genes identified both alleviating and aggravating interactions that
      could be divided into seven distinct categories. Owing to the wide activity of
      the Mariner transposon, Tn-seq has the potential to contribute to the exploration
      of complex pathways across many different species.

PMID- 19767759
TI  - An approach for extensibly profiling the molecular states of cellular
      subpopulations.
AB  - Microscopy often reveals the existence of phenotypically distinct cellular
      subpopulations. However, additional characterization of observed subpopulations
      can be limited by the number of biomolecular markers that can be simultaneously
      monitored. Here we present a computational approach for extensibly profiling
      cellular subpopulations by freeing one or more imaging channels to monitor
      additional probes. In our approach, we trained classifiers to re-identify
      subpopulations accurately based on an enhanced collection of phenotypic features
      extracted from only a subset of the original markers. Then we constructed
      subpopulation profiles step-wise from replicate experiments, in which cells were
      labeled with different but overlapping marker sets. We applied our approach to
      identify molecular differences among subpopulations and to identify functional
      groupings of markers, in populations of differentiating mouse preadipocytes,
      polarizing human neutrophil-like cells and dividing human cancer cells.

PMID- 19767761
TI  - Does needle calibre affect pain and complication rates in patients undergoing
      transperineal prostate biopsy? A prospective, randomized trial.
AB  - Transperineal prostate biopsy is a procedure that can be used to obtain
      histological samples from the prostate. To improve both the quality of the biopsy
      core samples and prostate cancer detection, we are currently performing a
      prospective, randomized trial comparing prostate biopsy samples obtained using an
      18 G-needle to those obtained using a 16 G needle. The aim of this preliminary
      study was to evaluate pain and complication rates in both groups in order to
      assess whether performing a prostate biopsy with a larger calibre needle is a
      feasible procedure. One hundred and eighty-seven patients undergoing
      transperineal prostate biopsy were prospectively evaluated and divided into two
      groups. The first group (94 patients, Group A) received a transperineal prostate
      biopsy using a 16 G-needle and the second group (93 patients, Group B) underwent
      transperineal prostate biopsy with an 18 G-needle. Anaesthesia was obtained with
      a single perineal injection at the prostatic apex in all subjects. A visual
      analogue scale (VAS) and facial expression scale (FES) were used to assess pain
      during multiple steps of the procedure in each group. A detailed questionnaire
      was used to obtain information about drug use because it could potentially
      influence the pain and complications that patients experienced. Two weeks after
      the procedure, early and late complications were evaluated. Statistical analysis
      was carried out using non-parametric tests. Prostate Specific Antigen (PSA) and
      drug use were similar at baseline between the two groups. Pain during prostate
      biopsy, which was measured with both the VAS and FES instruments, did not differ
      significantly between the 18- and 16 G-needle groups, and no significant
      differences were found in early or late complication rates between the groups.
      Transperineal prostate biopsy with a 16 G-needle is a feasible procedure in terms
      of pain and complication rates. Further studies with larger patient populations
      are required to assess whether or not this procedure can improve prostate cancer
      detection rates.

PMID- 19767760
TI  - Uptake of resveratrol and role of resveratrol-targeting protein, quinone
      reductase 2, in normally cultured human prostate cells.
AB  - Resveratrol is a dietary polyphenol espoused to have chemopreventive activity
      against a variety of human cancer types. We first reported that resveratrol
      significantly decreases the proliferation of both androgen-dependent and hormone
      refractory prostate cancer cells. However, the effects of resveratrol in normal
      prostate epithelial and stromal cells, particularly with regard to its uptake,
      subcellular distribution and intracellular targets, have not been investigated.
      To advance the knowledge on accessibility and cellular disposition of resveratrol
      in prostate cells, [(3)H] resveratrol, fractionation of cell extracts into
      subcellular compartments, Western blot analysis, resveratrol affinity column
      chromatography and flow cytometry were used to study the uptake and intracellular
      distribution of resveratrol in normally cultured prostate stromal (PrSCs) and
      epithelial cells (PrECs). Pretreatment of both PrSCs and PrECs for 2 days with
      resveratrol modulated its uptake and selectively increased its distribution to
      the membrane and organelle compartments. Resveratrol affinity column
      chromatography studies showed differential expression of a previously identified
      resveratrol-targeting protein, quinone reductase 2 (QR2), in PrSCs and PrECs.
      Flow cytometric analysis comparing resveratrol-treated and untreated PrSCs showed
      a large decrease in G(1)-phase and a concomitant increase in S and G(2)/M-phases
      of the cell cycle. These results suggest that resveratrol suppresses PrSC
      proliferation by affecting cell cycle phase distribution, which may involve the
      participation by QR2.

PMID- 19767762
TI  - An overview on ethical issues about sperm donation.
AB  - Beyond the scientific progress in assisted reproductive technologies (ART), it is
      necessary to discuss the ethical considerations behind these advances. Ethical
      issues concerning sperm donation have been considered and discussed by government
      and non-governmental agencies, the public, media and academic institutions in
      many countries. Recommendations and guidelines concerning sperm donation issues
      vary from country to country and between professional groups within countries.
      This paper attempts to present an overview of findings and reports from various
      agencies concerning the ethics of sperm donation. The following topics are
      considered: limiting the number of donor offspring; minimizing risk of infection
      and genetics from sperm donors; age requirements for sperm donors; and anonymity
      versus non-anonymity of sperm donors. The diversity of policies shows that each
      country has its unique set of guidelines tailored toward its own specific needs.
      Similarly, countries designing their own procedures and guidelines concerning
      reproductive medicine must tailor them toward their own needs and practical
      considerations. In Mainland China, the anonymous policy for sperm donation should
      still be carried out, and the number of donor offspring should be revaluated. ART
      procedures must be conducted in a way that is respectful of those involved.
      Ethical principles must respect the interests and welfare of persons who will be
      born as well as the health and psychosocial welfare of all participants,
      including sperm donors.

PMID- 19767763
TI  - Effects of obesity on lower urinary tract symptoms in Korean BPH patients.
AB  - We analyzed the effects of obesity on lower urinary tract symptoms (LUTSs) in
      Korean benign prostatic hyperplasia (BPH) patients. This is a multicenter, cross
      sectional, prospective study conducted in four centers in Korea. A total of 602
      men with LUTSs secondary to BPH were included. BPH/LUTSs cases were men aged >/=
      40 years with international prostate symptom scores (IPSS) > or = 8 points.
      Height, weight and waist circumference were measured. Among the 602 patients, 156
      patients had a waist circumference above 90 cm, representing central obesity, and
      215 patients had a body mass index above 25 kg m(-2). Waist circumference was
      positively correlated with prostate volume (P = 0.034). Men with waist
      circumference > 90 cm experienced a 1.36-fold increased risk of severe LUTSs (95%
      CI 0.82-2.41) compared with men with waist circumference < or = 90 cm. Prostate
      volume was positively correlated with urgency and nocturia in men with central
      obesity. In this population of Korean men diagnosed with BPH, central obesity
      rather than overall obesity seems to be the more important predictor of LUTSs
      correlated with BPH.

PMID- 19767764
TI  - Characterization of cardamonin metabolism by P450 in different species via HPLC
      ESI-ion trap and UPLC-ESI-quadrupole mass spectrometry.
AB  - AIM: To characterize the metabolism of cardamonin by the P450 enzymes in human
      and animal liver microsomes. METHODS: Cardamonin was incubated with both human
      and animal liver microsomal incubation systems containing P450 reaction factors.
      High performance liquid chromatography coupled with ion trap mass spectrometry
      was used to identify the metabolites. Serial cardamonin dilutions were used to
      perform a kinetic study in human liver microsomes. Selective inhibitors of 7 of
      the major P450 isozymes were used to inhibit cardamonin hydroxylation to identify
      the isozymes involved in cardamonin metabolism. The cardamonin hydroxylation
      metabolic capacities of human and various other animals were investigated using
      the liver microsomal incubation system. RESULTS: Two metabolites generated by the
      liver microsome system were detected and identified as hydroxylated cardamonin.
      The Km and Vmax values for cardamonin hydroxylation were calculated as 32
      micromol/L and 35 pmol x min(-1) x mg(-1), respectively. Furafylline and
      clomethiazole significantly inhibited cardamonin hydroxylation. Guinea pigs
      showed the highest similarity to humans with respect to the metabolism of
      cardamonin. CONCLUSION: CYP 1A2 and 2E1 were identified as the P450 isozymes
      involved in the metabolism of cardamonin in human liver microsomes. Furthermore,
      our research suggests that guinea pigs could be used in the advanced
      pharmacokinetic studies of cardamonin in vivo.

PMID- 19767765
TI  - Glutamate receptors in the dorsal hippocampus mediate the acquisition, but not
      the expression, of conditioned place aversion induced by acute morphine
      withdrawal in rats.
AB  - AIM: To evaluate the role of glutamate receptors in the dorsal hippocampus (DH)
      in the motivational component of morphine withdrawal. METHODS: NMDA receptor
      antagonist D-AP5 (5 microg/0.5 microL per side) or AMPA receptor antagonist NBQX
      (2 microg/0.5 microL per side) was microinjected into DH of rats. Conditioned
      place aversion (CPA) induced by naloxone-precipitated morphine withdrawal were
      assessed. RESULTS: Preconditioning microinjection of D-AP5 or NBQX into the DH
      impaired the acquisition of CPA in acute morphine-dependent rats. However, intra
      DH microinjection of D-AP5 or NBQX after conditioning but before the testing
      session had no effect on the expression of CPA. CONCLUSION: Our results suggest
      that NMDA and AMPA receptors in the dorsal hippocampus are involved in the
      acquisition, but not in the expression, of the negative motivational components
      of acute morphine withdrawal in rats.

PMID- 19767753
TI  - Identification of seven new prostate cancer susceptibility loci through a genome
      wide association study.
AB  - Prostate cancer (PrCa) is the most frequently diagnosed cancer in males in
      developed countries. To identify common PrCa susceptibility alleles, we
      previously conducted a genome-wide association study in which 541,129 SNPs were
      genotyped in 1,854 PrCa cases with clinically detected disease and in 1,894
      controls. We have now extended the study to evaluate promising associations in a
      second stage in which we genotyped 43,671 SNPs in 3,650 PrCa cases and 3,940
      controls and in a third stage involving an additional 16,229 cases and 14,821
      controls from 21 studies. In addition to replicating previous associations, we
      identified seven new prostate cancer susceptibility loci on chromosomes 2, 4, 8,
      11 and 22 (with P = 1.6 x 10(-8) to P = 2.7 x 10(-33)).

PMID- 19767766
TI  - Atorvastatin attenuates homocysteine-induced apoptosis in human umbilical vein
      endothelial cells via inhibiting NADPH oxidase-related oxidative stress-triggered
      p38MAPK signaling.
AB  - AIM: To examine the effect of atorvastatin on homocysteine (Hcy)-induced reactive
      oxygen species (ROS) production and apoptosis in human umbilical vein endothelial
      cells (HUVECs). METHODS: HUVECs were cultured with Hcy (0.1-5 mmol/L) in the
      presence or absence of atorvastatin (1-100 micromol//L) or various stress
      signaling inhibitors, including the nicotinamide adenine dinucleotide phosphate
      (NADPH) oxidase inhibitor diphenylene iodonium (DPI, 10 micromol/L), the p38
      mitogen-activated protein kinase (p38 MAPK) inhibitor SB203580 (10 micromol/L)
      and antioxidants N-acetyl cysteine (NAC, 1 mmol/L). Cell apoptosis was evaluated
      by Annexin V/propidium iodide staining and flow cytometry. ROS were detected by
      2',7'-dichlorodihydrofluorescein diacetate (H(2)DCFH-DA). NADPH oxidases were
      evaluated with lucigenin-enhanced chemiluminescence. Hcy-induced expression of
      p38MAPK protein was measured by Western blotting analysis. RESULTS: Atorvastatin
      inhibited endothelial cell apoptosis induced by 1 mmol/L Hcy in a dose-dependent
      manner and the maximal inhibitory effect was reached at 100 micromol/L.
      Atorvastatin (10 micromol/L) significantly suppressed Hcy (1 mmol/L for 30 min)
      induced ROS accumulation (3.17+/-0.33 vs 4.34+/-0.31, P<0.05). Atorvastatin (10
      micromol/L) also antagonized Hcy (1 mmol/L for 30 min) induced activation of
      NADPH oxidase (2.57+/-0.49 vs 3.33+/-0.6, P<0.05). Furthermore, atorvastatin
      inhibited Hcy-induced phosphorylation of p38 MAPK (1.7+/-0.1 vs 2.22+/-0.25,
      P<0.05), similar effects occurred with DPI, NAC and SB203580. CONCLUSION:
      Atorvastatin may inhibit Hcy-induced ROS accumulation and endothelium cell
      apoptosis through an NADPH oxidase and/or p38MAPK-dependent mechanisms, all of
      which may contribute to atorvastatin-induced beneficial effect on endothelial
      function.

PMID- 19767767
TI  - A comparative study of outcomes of idarubicin- and etoposide-intensified
      conditioning regimens for allogeneic peripheral blood stem cell transplantation
      in patients with high-risk acute leukemia.
AB  - AIM: To analyze the results of idarubicin (IDA)- versus etoposide (VP16)
      intensified myeloablative conditioning regimen in allogeneic hematopoietic stem
      cell transplantation (allo-SCT) for high-risk acute leukemia. METHODS: From
      January 2005 to June 2008, 48 consecutive patients (male: n=29; median age: 30
      years, range 14-51 years) with high-risk acute leukemia underwent allo-SCT
      following an IDA- or VP16-intensified conditioning regimen. The conditioning
      regimens were modified BUCY2 (busulfan+cyclophosphamide) consisting of IDA (15
      mg/m2 per day, days -12 to -10) or VP16 (25 mg/kg per day, days -3 to -2) and
      CY/TBI (cyclophosphamide/total body irradiation) intensified with IDA (15 mg/m2
      per day, days -6 to -5) or VP16 (25 mg/kg per day, days -3 to -2) for acute
      myeloid leukemia and acute lymphoblastic leukemia, respectively. RESULTS: Between
      the two groups, no significant differences in terms of baseline characteristics,
      incidence of acute or chronic graft-versus-host disease (GVHD) or transplant
      related mortality (TRM) (P=0.50) were observed. However, the IDA group
      demonstrated higher incidences of mucositis and Aspergillus pneumonia (P<0.01 and
      P=0.03, respectively). For the IDA and VP16 groups, relapse rates were 28% and
      50%, respectively (P=0.13). For the same groups, the 2-year probabilities of
      leukemia-free survival (LFS) and overall survival (OS) were 72% versus 51%
      (P=0.04) and 74% versus 53% (P=0.04), respectively. CONCLUSION: This
      retrospective analysis suggests that conditioning regimens intensified with IDA
      can achieve better outcomes than conditioning regimens with VP16 in patients
      preparing to undergo allo-SCT for high-risk acute leukemia.

PMID- 19767769
TI  - Pbx1 is a downstream target of Evi-1 in hematopoietic stem/progenitors and
      leukemic cells.
AB  - Ecotropic viral integration site-1 (Evi-1) is a nuclear transcription factor,
      which is essential for the proliferation/maintenance of hematopoietic stem cells
      (HSCs). Aberrant expression of Evi-1 has been frequently found in myeloid
      leukemia, and is associated with a poor patient survival. Recently, we reported
      candidate target genes of Evi-1 shared in HSCs and leukemic cells using gene
      expression profiling analysis. In this study, we identified Pbx1, a proto
      oncogene in hematopoietic malignancy, as a target gene of Evi-1. Overexpression
      of Evi-1 increased Pbx1 expression in hematopoietic stem/progenitor cells. An
      analysis of the Pbx1 promoter region revealed that Evi-1 upregulates Pbx1
      transcription. Furthermore, reduction of Pbx1 levels through RNAi-mediated
      knockdown significantly inhibited Evi-1-induced transformation. In contrast,
      knockdown of Pbx1 did not impair bone marrow transformation by E2A/HLF or
      AML1/ETO, suggesting that Pbx1 is specifically required for the maintenance of
      bone marrow transformation mediated by Evi-1. These results indicate that Pbx1 is
      a target gene of Evi-1 involved in Evi-1-mediated leukemogenesis.

PMID- 19767770
TI  - A novel pro-apoptotic function of RACK1: suppression of Src activity in the
      intrinsic and Akt pathways.
AB  - Earlier we showed that RACK1 regulates growth of human colon cells by suppressing
      Src activity at G(1) and mitotic checkpoints. Here, we show that RACK1 also
      induces apoptosis of the cells, partly by inhibiting Src. In the intrinsic
      pathway, RACK1 inhibits expression of anti-apoptotic Bcl-2 and Bcl-X(L), induces
      expression of pro-apoptotic Bim, targets Bim and Bax to the mitochondria, induces
      oligomerization of Bax (which requires Bim and inhibition of Src), depolarizes
      mitochondria membranes, releases cytochrome c, and activates caspases-9 and -3
      and death substrates. Bax and Bim are required for RACK1-mediated mitochondrial
      cell death. RACK1-induced oligomerization of Bax is required for staurosporine
      mediated cell death. RACK1 also induces apoptosis by blocking Src activation of
      the Akt cell survival pathway. This leads to activation of the transcription
      factor FOXO3, a potent inducer of apoptosis and G(1) arrest. Collectively, our
      results show that RACK1, partly by inhibiting Src, promotes mitochondrial cell
      death and blocks Akt-mediated cell survival. Thus, RACK1 inhibits growth and
      induces death of colon cells. Exploitation of these dual functions could lead to
      novel colon cancer therapies that mimic RACK1 function.

PMID- 19767768
TI  - YKL-40, a secreted glycoprotein, promotes tumor angiogenesis.
AB  - Tumor angiogenesis is of paramount importance in solid tumor development.
      Elevated serum levels of YKL-40, which is a secreted heparin-binding
      glycoprotein, have been associated with a worse prognosis from various advanced
      human cancers. Yet the role of YKL-40 activity in these cancers is still missing.
      In this study, we showed that ectopic expression of YKL-40 in MDA-MB-231 breast
      cancer cells and in HCT-116 colon cancer cells led to larger tumor formation with
      an extensive angiogenic phenotype than did control cancer cells in mice. Affinity
      purified recombinant YKL-40 protein promoted vascular endothelial cell
      angiogenesis in vitro, the effects of which are similar to the activities
      observed using MDA-MB-231 and HCT-116 cell-conditioned medium after transfection
      with YKL-40. Furthermore, YKL-40 was found to induce coordination of membrane
      bound receptor syndecan-1 and integrin alpha(v)beta(3) and to activate an
      intracellular signaling cascade, including focal adhesion kinase and mitogen
      activated protein kinase extracellular signal-related kinase1/2 in endothelial
      cells. Moreover, blockade of YKL-40 using small-interfering RNA gene knockdown
      suppressed tumor angiogenesis in vitro and in vivo. Immunohistochemical analysis
      of human breast cancer showed a correlation between YKL-40 expression and blood
      vessel density. These findings provide novel insights into angiogenic activities
      and molecular mechanisms of YKL-40 in cancer development.

PMID- 19767772
TI  - Regulation of miRNA expression by Src and contact normalization: effects on
      nonanchored cell growth and migration.
AB  - Transformation by the Src tyrosine kinase (Src) promotes nonanchored cell growth
      and migration. However, nontransformed cells can force Src-transformed cells to
      assume a normal morphology and phenotype by a process called 'contact
      normalization'. It has become clear that microRNA (miRNA) can affect
      tumorigenesis by targeting gene products that direct cell growth and migration.
      However, the roles of miRNA in Src transformation or contact normalization have
      not yet been reported. We examined the expression of 95 miRNAs and found 9 of
      them significantly affected by Src. In this study, we report that miR-218 and miR
      224 were most significantly induced by Src, but not affected by contact
      normalization. In contrast, miR-126 was most significantly suppressed by Src and
      was induced by contact normalization in transformed cells. Mir-126 targets Crk, a
      component of the focal adhesion network that participates in events required for
      tumor cell migration. Accordingly, we show that miR-126 expression correlates
      inversely with Crk levels, motility and the invasive potential of human mammary
      carcinoma cells. Moreover, we show that miR-224 expression promotes nonanchored
      growth of nontransformed cells. These data reveal novel insights into how Src
      regulates miRNA expression to promote hallmarks of tumor cell growth and
      invasion, and how nontransformed cells can affect miRNA expression in adjacent
      tumor cells to inhibit this process.

PMID- 19767771
TI  - Transcription activity is required for p53-dependent tumor suppression.
AB  - As a transcription factor, the critical tumor suppressor, p53, directly regulates
      the transcription of hundreds of genes, leading to cell-cycle arrest, apoptosis,
      cellular senescence and differentiation. Although it has been assumed that p53
      transcription activity is critical for tumor suppression, this assumption has
      been increasingly contested by recent findings of transcription-independent roles
      of p53 in apoptosis as well as findings that none of the mutant mice lacking
      important p53 transcription targets are cancer prone. On the basis of previous
      findings that p53 transcription activity is abolished in p53(QS) (Leu25Trp26 to
      Gln25Ser26) knock-in mouse cells after DNA damage, to determine the importance of
      transcription activity of p53 in tumor suppression, we generated knock-in mice
      that can conditionally express p53(QS) protein in a Cre-dependent manner. By
      breeding the knock-in mice with Lck-Cre transgenic mice that specifically express
      Cre in thymocytes, we show that p53-dependent suppression of thymic lymphomas is
      abolished in thymocytes expressing high levels of p53(QS) protein. In addition,
      p53(QS) protein is accumulated in some of the thymic tumors. Therefore, p53
      transcription activity induced by DNA damage is required for tumor suppression.
      Together with the findings that the disruption of various p53-dependent functions
      individually fails to promote cancer, our findings indicate that various
      transcription-dependent functions of p53 must collaborate to efficiently suppress
      tumorigenesis.

PMID- 19767773
TI  - Heat shock protein 27 mediates repression of androgen receptor function by
      protein kinase D1 in prostate cancer cells.
AB  - We have previously shown that protein kinase D1 (PKD1), charter member of PKD
      protein family, is downregulated in advanced prostate cancer (PC) and influences
      androgen receptor (AR) function in PC cells. Other independent studies showed
      that serine 82 residue in heat shock protein 27 (Hsp27) undergoes substrate
      phosphorylation by PKD1 and is associated with nuclear transport of AR resulting
      in increased AR transcriptional activity. In this study, we show that PKD1
      interacts and phosphorylates Hsp27 at Ser82 in PC cells, which is mediated by p38
      dependent mitogen-activated protein kinase pathway and is necessary for PKD1
      repression of AR transcriptional activity and androgen-dependent proliferation of
      PC cells. The study provides first in vivo evidence that Hsp27 is a mediator of
      repression of AR function by PKD1 in PC cells, thereby linking the data in the
      published literature.

PMID- 19767774
TI  - 'Loss of pigment epithelium-derived factor enables migration, invasion and
      metastatic spread of human melanoma'.
AB  - Pigment epithelium-derived factor (PEDF) is a multifunctional secreted
      glycoprotein that displays broad anti-tumor activity based on dual targeting of
      the tumor microenvironment (anti-angiogenic action) and the tumor cells (direct
      anti-tumor action). Here, we show that PEDF expression is high in melanocytes,
      but it is lost during malignant progression of human melanoma. Using a high
      throughput analysis of the data from microarray studies of molecular profiling of
      human melanoma, we found that PEDF expression is lost in highly invasive
      melanomas. In paired cell lines established from the same lesion but representing
      the high and low extremes of malignant potential, abundant PEDF expression was
      restricted to the poorly aggressive counterparts. We used RNA interference to
      directly address the functional consequences of PEDF silencing. PEDF knockdown in
      poorly aggressive melanoma cell lines augmented migration, invasion and
      vasculogenic mimicry, which translated into an increased in vivo metastatic
      potential. PEDF interference also significantly enhanced the migratory and
      invasive capability of normal melanocytes and moderately increased their
      proliferative potential. Our results show that loss of PEDF enables melanoma
      cells to acquire an invasive phenotype and, therefore, modulation of this
      multifunctional factor could be critical for the malignant progression of human
      melanoma.

PMID- 19767776
TI  - Loss-of-function genetic screens as a tool to improve the diagnosis and treatment
      of cancer.
AB  - A major impediment to the effective treatment of cancer is the molecular
      heterogeneity of the disease, which is also reflected in an equally diverse
      pattern of clinical responses to therapy. Currently, only few drugs are available
      that can be used safely and effectively to treat cancer. To improve this
      situation, the development of novel and highly specific targets for therapy is of
      utmost importance. Possibly even more importantly, we need better tools to
      predict which patients will respond to specific therapies. Such drug response
      biomarkers will be instrumental to individualize the therapy of patients having
      seemingly similar cancers. In this study, we discuss how RNA interference-based
      genetic screens can be used to address these two pressing needs in the care for
      cancer patients.

PMID- 19767775
TI  - Lysine 269 is essential for cyclin D1 ubiquitylation by the SCF(Fbx4/alphaB
      crystallin) ligase and subsequent proteasome-dependent degradation.
AB  - Protein ubiquitylation is a complex enzymatic process that results in the
      covalent attachment of ubiquitin, through Gly-76 of ubiquitin, to an
      varepsilonNH2 group of an internal lysine residue in a given substrate. Although
      E3 ligases frequently use lysines adjacent to the degron within the substrate,
      many substrates can be targeted to the proteasome through the polyubiquitylation
      of any lysine. We have assessed the role of lysine residues proximal to the
      cyclin D1 phosphodegron for ubiquitylation by the SCF(Fbx4/alphaB-crystallin)
      ubiquitin ligase and subsequent proteasome-dependent degradation of cyclin D1.
      The work described herein reveals a requisite role for Lys-269 (K269) for the
      rapid polyubiquitin-mediated degradation of cyclin D1. Mutation of Lys-269, which
      is proximal to the phosphodegron sequence surrounding Thr-286 in cyclin D1, not
      only stabilizes cyclin D1 but also triggers cyclin D1 accumulation within the
      nucleus, thereby promoting cell transformation. In addition, D1-K269R is
      resistant to genotoxic stress-induced degradation, similar to non
      phosphorylatable D1-T286A, supporting the critical role for the post
      translational regulation of cyclin D1 in response to DNA-damaging agents.
      Strikingly, although mutation of lysine 269 to arginine inhibits cyclin D1
      degradation, it does not inhibit cyclin D1 ubiquitylation in vivo, showing that
      ubiquitylation of a specific lysine can influence substrate targeting to the 26S
      proteasome.

PMID- 19767777
TI  - Monoclonal B cells detected in autologous PBSC grafts from patients with
      classical Hodgkin lymphoma: impact on relapse and survival following
      transplantation.
AB  - Autologous peripheral blood stem cell transplantation (PBSCT) for Hodgkin
      lymphoma (HL) is curative for many patients with relapsed or refractory disease.
      Relapsing disease, however, remains a major problem. Neoplastic transformation of
      B-lymphocytes probably underlies the development of classical HL. Whether clonal
      B cells are critical for disease evolution and response to therapy in HL remains
      uncertain. We investigated the impact of clonal B cells detected in peripheral
      blood stem cell (PBSC) collections on the outcome of patients with HL undergoing
      transplant. Qualitative semi-nested PCR was carried out on genomic DNA from
      mononuclear cells from PBSCs to determine the presence of clonal immunoglobulin
      heavy chain (IgH) complementary-determining region 3 (CDR3) gene rearrangements.
      Clinical factors were assessed for their association with relapse, overall
      survival (OS) and progression-free survival (PFS). Among 39 patients undergoing
      PBSCT, 12 grafts (31%) were PCR positive for clonal IgH rearrangements. OS was
      better in the PCR-negative group (logrank test, P=0.041). The OS at 5 years was
      81% in PCR-negative versus 39% in PCR-positive patients; hazard ratio was 3.23
      (95% confidence interval: 0.98-10.63). There was a trend towards better PFS
      (logrank test, P=0.12), estimated as 71% at 5 years in PCR-negative versus 41% in
      PCR-positive patients. Clonal B-lymphocytes in PBSC collections of patients with
      HL identify patients at risk of poor outcome. Larger series are needed to confirm
      our observations. Insight regarding the role of monoclonal B cells may lead to
      improved therapies.

PMID- 19767778
TI  - Improved outcome of refractory Langerhans cell histiocytosis in children with
      hematopoietic stem cell transplantation in Japan.
AB  - Langerhans cell histiocytosis (LCH) that is refractory to conventional
      chemotherapy has a poor outcome. Hematopoietic stem cell transplantation (SCT) is
      a promising approach for refractory LCH because of its immunomodulatory effect.
      In this study, the outcomes of children with refractory LCH undergoing SCT in
      Japan were analyzed. Between November 1995 and March 2007, 15 children younger
      than 15 years (9 males, 6 females) with refractory LCH underwent SCT. The
      patients' median age at diagnosis was 8 months (range, 28 days to 28 months), and
      all had failed conventional chemotherapy. The median age at SCT was 23 months
      (range, 13-178 months). Nine had risk organ involvement at diagnosis, including
      liver (n=6), spleen (n=5), lung (n=5), and/or hematopoietic system (n=4). For
      SCT, a myeloablative regimen was used for 10 patients, and a reduced-intensity
      conditioning regimen (RIC) was used for five. The donor source varied among the
      patients, but allogeneic cord blood was primarily used (n=10). Subsequently, 11
      of 15 patients have survived with no evidence of disease, with a 10-year overall
      survival (OS) rate (median+/-standard error) of 73.3+/-11.4%. The 10-year OS rate
      of nine patients with risk organ involvement at diagnosis was 55.6+/-16.6%,
      whereas six without risk organ involvement have all survived with no evidence of
      disease (P=0.07). These results indicate that SCT is promising as a salvage
      approach for children with refractory LCH.

PMID- 19767779
TI  - Successful treatment of transplantation-associated thrombotic microangiopathy
      with recombinant human soluble thrombomodulin.

PMID- 19767780
TI  - Excessive toxicity of once daily i.v. BU, melphalan and thiotepa followed by auto
      SCT on patients with non-Hodgkin's lymphoma.

PMID- 19767781
TI  - Outpatient myeloablative allo-SCT: a comprehensive approach yields decreased
      hospital utilization and low TRM.
AB  - Historically, myeloablative allogeneic hematopoietic SCT (HSCT) has required
      prolonged in-patient hospitalization due to the effects of mucosal toxicity and
      prolonged cytopenias. We explored the safety and feasibility of outpatient
      management of these patients. A total of 100 consecutive patients underwent a
      matched-related donor myeloablative allogeneic HSCT for a hematologic malignancy
      at a single institution. Patients were hospitalized briefly for stem-cell
      infusion and thereafter only for complications more safely managed in the in
      patient setting. The median hospital length of stay from the start of the
      preparative regimen to day +30 and day +100 post-transplant was 12 and 15 days,
      respectively. Planned hospital discharge occurred in 79 patients after stem cell
      infusion. Patients were readmitted to hospital at median of day +7 post
      transplant, with neutropenic fever being the primary cause for readmission. In
      total, 18 patients required no in-patient care in the first 100 days. Non-relapse
      mortality at day 100 and 6 months was 10 and 15%, respectively, for all patients,
      and 0 and 5%, respectively, for standard risk patients. In summary, outpatient
      myeloablative allogeneic HSCT with expectant in-patient management can be
      accomplished safely with low treatment-related morbidity and mortality. Clinical
      outcomes seem comparable to those reported for traditional in-patient management.

PMID- 19767782
TI  - Impact of pretransplant comorbidities on alemtuzumab-based reduced-intensity
      conditioning allogeneic hematopoietic SCT for patients with high-risk
      myelodysplastic syndrome and AML.
AB  - We report a retrospective analysis of 128 consecutive patients with high-risk
      myelodysplastic syndrome (MDS) and AML who received an alemtuzumab-based reduced
      intensity conditioning hematopoietic SCT (RIC HSCT). The median recipient age was
      53 years (range 21-72 years). A total of 49 (38%) recipients had a sibling donor
      and 79 (62%) had a volunteer-unrelated donor. The hematopoietic cell
      transplantation-specific comorbidity index (HCT-CI) was assigned to all patients
      with a score of 0 in 40 (31%), of 1-2 in 45 (35%) and >or=3 in 43 (34%) patients.
      The 3-year non-relapse mortality (NRM) was 31%, disease-free survival (DFS) was
      41% and overall survival (OS) was 46%. The 3-year NRM for patients with a HCT-CI
      score of 0, 1-2 or >or=3 was 16, 24 and 42%, respectively. The 3-year DFS and OS
      by HCT-CI was 58 and 69% (score 0), 39 and 39% (score 1-2) and 24 and 32% (score
      >or=3), respectively. On multivariate analysis, HCT-CI was an independent
      variable affecting 3-year NRM, DFS and OS (P-value=0.04, 0.01 and <0.01,
      respectively). Although the disease stage at the time of transplant was an
      additional independent predictive variable on transplant outcomes, recipient age
      (>or<50 years) did not have a significant predictive impact. In MDS or AML
      patients with advanced disease receiving alemtuzumab-based RIC HSCT, the HCT-CI
      provides an important means of stratifying patients with a high risk of inferior
      transplant outcomes.

PMID- 19767783
TI  - Mycophenolate mofetil for the management of steroid-refractory acute graft vs
      host disease.
AB  - Acute graft vs host disease (aGVHD) is a significant obstacle to successful
      allogeneic hematopoietic cell transplantation, as only 30-40% of those with aGVHD
      show complete response to front-line glucocorticoids. The role of mycophenolate
      mofetil (MMF) as salvage therapy in steroid-refractory aGVHD remains incompletely
      defined. Here, we examine outcomes of 27 patients with refractory aGVHD treated
      with MMF as second-line therapy. Seven (26%) patients achieved complete remission
      (CR) of steroid-refractory aGVHD with only the addition of MMF as salvage
      therapy. CR of aGVHD differed by overall grade at salvage (grade I, 1/3; grade
      II, 5/12; grade III 0/5; grade IV, 1/7) with odds ratio for CR in grade I/II vs
      III/IV of 7.3 (95% CI: 0.7-72.6, P=0.09). Overall survival (OS) at 3 years was
      40%. Overall aGVHD grade at salvage (hazard ratio (HR) grade I/II vs III/IV 0.18
      (95% CI: 0.06-0.57), P=0.003) and achievement of CR (HR 0.12 (95% CI: 0.04-0.39),
      P=0.0004) were significant predictors of OS. MMF was overall well tolerated, with
      only two patients requiring discontinuation for myelosuppression. MMF shows
      activity in the salvage of steroid-refractory, grades I-II aGVHD.

PMID- 19767784
TI  - High-dose chemotherapy and hematopoietic SCT in the management of natural killer
      cell malignancies.
AB  - Natural killer (NK)-cell lymphomas are aggressive. Patients with early (stage
      I/II) diseases respond favorably to radiotherapy and chemotherapy. Patients with
      relapses and advanced (stage III/IV) diseases have poor outcome. To improve
      treatment results, high-dose chemotherapy with hematopoietic SCT (HSCT) has been
      performed. A review of 57 published cases of autologous HSCT showed the status
      pre-HSCT as the only significant prognostic factor. HSCT at CR had the best
      survival. As patients achieving CR with chemotherapy and radiotherapy also have
      favorable outcome, a definite advantage of autologous HSCT cannot be established.
      Patients with advanced, relapsed or refractory diseases had dismal survivals
      after autologous HSCT. Allogeneic HSCT had been reported in about 30 patients,
      with a 2-year OS of 40%. To evaluate the efficacy of allogeneic HSCT, optimal
      conditioning regimens and a clear graft-versus-lymphoma effect should be defined.
      Furthermore, clinicopathological characteristics predicting benefits from
      allogeneic HSCT need to be determined. HSCT is a potential option in NK-cell
      lymphoma. However, autologous HSCT may not be necessary for good-risk patients in
      CR. Whether poor risk patients will have improved outcome with autologous HSCT
      remains to be defined. The role of allogeneic HSCT requires more rigorous future
      studies.

PMID- 19767785
TI  - Late acute renal failure due to bilateral kidney infiltration by ALL as single
      manifestation of relapse after allogeneic transplantation.

PMID- 19767786
TI  - Brachial plexopathy following high-dose melphalan and autologous peripheral blood
      stem cell transplantation.

PMID- 19767787
TI  - Transplantation-associated thrombotic microangiopathy: effect of concomitant GVHD
      on efficacy of therapeutic plasma exchange.
AB  - Factors predictive of response to plasma exchange (PE) in treatment of
      transplantation-associated thrombotic microangiopathy (TA-TMA) are generally
      poorly understood. To determine any clinical or laboratory factors predictive of
      response to PE in treatment of TA-TMA, we retrospectively reviewed all 11 cases
      of TA-TMA treated with PE at out institution between December 2001 and March
      2008. Response to PE was correlated with associated clinical conditions, grade of
      TA-TMA, TA-TMA index and lactate dehydrogenase (LDH) level at diagnosis. Overall
      response to PE was 27%, with three complete responses (CRs) and eight non
      responses (NRs) seen. Response to PE was significantly associated with the
      absence of acute GVHD at TA-TMA diagnosis, with three CR in four patients without
      active acute GVHD, and NR in seven patients with acute GVHD (P=0.024). There was
      no significant association seen between response to PE grade of TA-TMA (P=0.179),
      TA-TMA index (P=0.25) or LDH measurements (P=0.31). Our experience in use of
      therapeutic PE for management of TA-TMA suggests that PE may indeed be effective
      in the treatment of this disorder, depending on the clinical circumstance in
      which it develops. PE is potentially efficacious in the absence of active acute
      GVHD, and ineffective when acute GVHD is manifest.

PMID- 19767788
TI  - Taste disorders and oral evaluation in patients undergoing allogeneic
      hematopoietic SCT.
AB  - The aim of this study was to evaluate taste perception, salivary flow rate and
      oral pathologies in three different groups of patients undergoing hematopoietic
      SCT (HSCT) classified according to time post transplant. Group I (n=20) up to 150
      days after HSCT, group II (n=20) between 151 and 1095 days and group III (n=21)
      more than 1095 days. Taste acuity was measured by four basic tastes of four
      solutions, in three concentrations (M): NaCl, sucrose, citric acid and caffeine.
      Patients classified flavors as sweet, sour, salty, bitter and without flavor. The
      intensity was considered high, medium and low. Unstimulated saliva was collected
      and salivary flow rates (ml/min) were determined. Of 61 patients, 31 had chronic
      GVHD. For the sweet solution, the high and low concentrations represented a
      challenge for those patients. No patients were sensitive to the low concentration
      of caffeine solution (P=0.05). Saliva flow rate was diminished in 10 of 61 (16%)
      patients and hyposalivation was more intense in groups II/III (P=0.007). There
      was no correlation between taste dysfunction and oral chronic GVHD. The results
      indicated taste alterations only for the sweet and salty tastes even in patients
      up to 3 years after HSCT and may not correlate with oral chronic GVHD and with
      hyposalivation.

PMID- 19767789
TI  - Prevention of overweight and obesity in children under the age of 6 years.
AB  - Although obesity was rarely observed among children 30 years ago, it is now
      evident among Canadian children of all ages. Currently, 15.2% of 2- to 5-year-old
      children are overweight, whereas 6.3% are obese. Limited data suggest that poor
      dietary and physical activity patterns are increasing obesity risk among these
      young children. Body weight and lifestyle behaviours are known to track from
      childhood to adulthood, thereby increasing the risk for obesity and other chronic
      diseases later in life. Intrauterine life, infancy, and the preschool years may
      all include critical periods that program the long-term regulation of energy
      balance, and therefore obesity-prevention strategies should be initiated in utero
      and continue throughout childhood and adolescence. Although single-strategy
      obesity-prevention initiatives have had limited success, programs that target
      multiple behaviours may help reduce body weight and body fat among young
      children. Parental involvement is key to the success of obesity-prevention
      programs at a young age, as parents have primary control over their children's
      food and activity environments. Accordingly, parental obesity is the best
      predictor of childhood obesity. Parents should be encouraged to teach and role
      model healthy lifestyle behaviours for their young children. Health professionals
      can also be involved in obesity prevention, as they are ideally placed to
      identify young children at risk for obesity. By calculating and plotting the body
      mass index for all children, and initiating obesity-prevention strategies in
      utero, health professionals can help curb the rise in overweight and obesity
      among young children.

PMID- 19767790
TI  - Physical activity and abdominal obesity in youth.
AB  - Childhood obesity continues to escalate despite considerable efforts to reverse
      the current trends. Childhood obesity is a leading public health concern because
      overweight-obese youth suffer from comorbidities such as type 2 diabetes
      mellitus, nonalcoholic fatty liver disease, metabolic syndrome, and
      cardiovascular disease, conditions once considered limited to adults. This
      increasing prevalence of chronic health conditions in youth closely parallels the
      dramatic increase in obesity, in particular abdominal adiposity, in youth.
      Although mounting evidence in adults demonstrates the benefits of regular
      physical activity as a treatment strategy for abdominal obesity, the independent
      role of regular physical activity alone (e.g., without calorie restriction) on
      abdominal obesity, and in particular visceral fat, is largely unclear in youth.
      There is some evidence to suggest that, independent of sedentary activity levels
      (e.g., television watching or playing video games), engaging in higher-intensity
      physical activity is associated with a lower waist circumference and less
      visceral fat. Several randomized controlled studies have shown that aerobic types
      of exercise are protective against age-related increases in visceral adiposity in
      growing children and adolescents. However, evidence regarding the effect of
      resistance training alone as a strategy for the treatment of abdominal obesity is
      lacking and warrants further investigation.

PMID- 19767791
TI  - High-dose diazepam facilitates core cooling during cold saline infusion in
      healthy volunteers.
AB  - Studies have suggested that inducing mild hypothermia improves neurologic
      outcomes after traumatic brain injury, major stroke, cardiac arrest, or
      exertional heat illness. While infusion of cold normal saline is a simple and
      inexpensive method for reducing core temperature, human cold-defense mechanisms
      potentially make this route stressful or ineffective. We hypothesized that
      intravenous administration of diazepam during a rapid infusion of 30 mL.kg-1 of
      cold (4 degrees C) 0.9% saline to healthy subjects would be more comfortable and
      reduce core body temperature more than the administration of cold saline alone.
      Fifteen subjects received rapidly infused cold (4 degrees C) 0.9% saline.
      Subjects were randomly assigned to receive, intravenously, 20 mg diazepam (HIGH),
      10 mg diazepam (LOW), or placebo (CON). Main outcomes were core temperature, skin
      temperature, and oxygen consumption. Data for the main outcomes were analyzed
      with generalized estimating equations to identify differences in group, time, or
      a group x time interaction. Core temperature decreased in all groups (CON, 1.0 +/
      0.2 degrees C; LOW, 1.4 +/- 0.2 degrees C; HIGH, 1.5 +/- 0.2 degrees C), while
      skin temperature was unchanged. Mean (95% CI) oxygen consumption was 315.3
      (253.8, 376.9) mL.kg-1.min-1 in the CON group, 317.9 (275.5, 360.3) in the LOW
      group, and 226.1 (216.4, 235.9) in the HIGH group. Significant time and group x
      time interaction was observed for core temperature and oxygen consumption (p <
      0.001). Administration of high-dose diazepam resulted in decreased oxygen
      consumption during cold saline infusion, suggesting that 20 mg of intravenous
      diazepam may reduce the shivering threshold without compromising respiratory or
      cardiovascular function.

PMID- 19767792
TI  - Effects of Ramadan fasting on physical performance and metabolic, hormonal, and
      inflammatory parameters in middle-distance runners.
AB  - The Ramadan fasting (RF) period is associated with changes in sleep habits and
      increased sleepiness, which may affect physical performance in athletes, and may
      induce metabolic, hormonal, and inflammatory disturbances. In 8 middle-distance
      athletes (25.0 +/- 1.3 years), a maximal aerobic velocity (MAV) test was
      performed 5 days before RF (day -5), and on days 7 and 21 of RF. The same days,
      saliva samples were collected to determine cortisol and testosterone
      concentrations before and after the MAV test. Blood samples were collected before
      RF (P1), at the end of RF (P2), and 1 week post RF (P3). Plasma levels of
      interleukin (IL)-6, a mediator of sleepiness and energy availability, were
      determined. We also evaluated changes in metabolic and hormonal parameters, mood
      state, and nutritional and sleep profiles. During RF, mean body mass and body fat
      did not statistically change. Compared with day -5, MAV values decreased at days
      7 and 21 (p < 0.05, respectively), while testosterone/cortisol ratio values did
      not change significantly. Nocturnal sleep time and energy intake were lower at
      day 21 than before RF (day 0/P1) (p < 0.05). At the end of RF (day 31), the
      fatigue score on the Profile of Mood States questionnaire was increased (p <
      0.001). For P2 vs. P1, IL-6 was increased (1.19 +/- 0.25 vs. 0.51 +/- 0.13 pg.mL
      1; p < 0.05), melatonin levels were decreased (p < 0.05), and adrenalin and
      noradrenalin were increased (p < 0.01 and p < 0.001, respectively). At 7 days
      post RF, all parameters recovered to pre-RF values. In conclusion, RF is
      accompanied by significant metabolic, hormonal, and inflammatory changes. Sleep
      disturbances, energy deficiency, and fatigue during RF may decrease physical
      performance in Muslim athletes who maintain training. Reduction of work load and
      (or) daytime napping may represent adequate strategies to counteract RF effects
      for Muslim athletes.

PMID- 19767793
TI  - Daily physical activity and macronutrient distribution of low-calorie diets
      jointly affect body fat reduction in obese women.
AB  - Inadequate dietary patterns and sedentary lifestyles are believed to be important
      factors in predisposing people to obesity. This study analyzed the potential
      interaction between habitual physical activity and the carbohydrate (CHO)-fat
      distribution in 2 hypocaloric diets and the impact of such interplay on body
      composition changes. Forty healthy obese women, 20-50 years old, were randomly
      assigned to a high- or low-CHO energy-restricted diet, which was low or high in
      fat, respectively, during 10 weeks. Baseline and final measurements were
      performed to assess dietary habits, resting metabolic rate, and body composition
      changes. Physical activity was measured with a triaxial accelerometer and with a
      questionnaire. There were no significant differences in anthropometric and
      metabolic variables between both dietary groups at baseline. However, there was a
      positive correlation between total free-living physical activity and arm muscle
      preservation after 10 weeks (r = 0.371; p = 0.024). Interestingly, an interaction
      between macronutrient (CHO-fat distribution) intake and physical activity was
      found, since less-active subjects with a high-CHO-low-fat diet showed a greater
      fat loss than those more active with a lower-CHO-high-fat diet, whereas more
      active subjects with a high-CHO-low-fat diet showed a smaller fat loss than those
      receiving a low-CHO-high-fat diet. Physical activity and the macronutrient
      content of energy-restricted diets, when designed to promote body fat mass
      reduction, should be considered together to better predict the outcome.

PMID- 19767794
TI  - Exercise-induced lymphocyte apoptosis attributable to cycle ergometer exercise in
      endurance-trained individuals.
AB  - Exercise as a stimulus to induce lymphocyte apoptosis remains controversial.
      Differences may be due to participant fitness level or the methodology of
      assessing cell death. Another important issue is the mode of exercise used to
      induce physiological changes. Treadmill exercise typically induces significant
      apoptosis in human lymphocytes; however, the effect of cycle exercise is less
      clear. The 2 main purposes of this study were to assess if cycle ergometer
      exercise induces similar changes in apoptosis, and to further characterize the
      morphological method of assessing cell death. Endurance athletes (n = 10; peak
      oxygen consumption = 55.1 mL.kg-1.min-1) completed a 60-min ride on a cycle
      ergometer at approximately 80% peak oxygen consumption. Blood samples taken
      before (PRE) and after (POST) exercise were used to make blood films for
      apoptotic analysis via the morphological technique. A significant increase was
      observed in the apoptotic index following cycle exercise (PRE = 7.3 +/- 2%, POST
      = 12.9 +/- 2%; p < 0.01). On average, it took 42 +/- 9 min to read PRE sample
      slides, which was significantly longer than the 27 +/- 4 min needed for POST
      slides (p < 0.01). To our knowledge, this study is the first to report that
      exercise on the cycle ergometer produces changes in lymphocyte apoptosis. The
      values measured during this study were about 20% lower than those we have
      observed following treadmill running, which may be explained by differences in
      active muscle mass and the resultant physiological stress between the 2 exercise
      modes. It is likely that cycling may result in reduced immunosuppression,
      compared with running at the same intensity.

PMID- 19767795
TI  - Child-adult differences in muscle strength and activation pattern during
      isometric elbow flexion and extension.
AB  - Muscle strength and activation were compared in boys and men during maximal
      voluntary elbow flexion and extension contractions. Peak torque, peak rate of
      torque development (d/dmax), rate of muscle activation, and electromechanical
      delay (EMD) were measured in 15 boys (aged 9.7 +/- 1.6 years) and 16 men (aged
      22.1 +/- 2.8 years). During flexion, peak torque was significantly lower in boys
      than in men (19.5 +/- 5.8 vs. 68.5 +/- 11.0 Nm, respectively; p < 0.05), even
      when controlling for upper-arm cross-sectional area (CSA), and peak
      electromyography activity. Boys also exhibited a lower normalized d/dmax (7.2 +/-
      1.7 vs. 9.5 +/- 1.6 (Nm.s-1).(Nm-1), respectively; p < 0.05) and a significantly
      longer EMD (75.5 +/- 28.4 vs. 47.6 +/- 17.5 ms, respectively). The pattern was
      similar for extension, except that group differences in peak torque were no
      longer significant when normalized for CSA. These results suggest that children
      may be less able to recruit or fully utilize their higher-threshold motor units,
      resulting in lower dimensionally normalized maximal torque and rate of torque
      development.

PMID- 19767796
TI  - The effects of increased endurance training load on biomarkers of heat
      intolerance during intense exercise in the heat.
AB  - The effects of increased training (IT) load on plasma concentrations of
      lipopolysaccharides (LPS), proinflammatory cytokines, and anti-LPS antibodies
      during exercise in the heat were investigated in 18 male runners, who performed
      14 days of normal training (NT) or 14 days of 20% IT load in 2 equal groups.
      Before (trial 1) and after (trial 2) the training intervention, all subjects ran
      at 70% maximum oxygen uptake on a treadmill under hot (35 degrees C) and humid
      (~40%) conditions, until core temperature reached 39.5 degrees C or volitional
      exhaustion. Venous blood samples were drawn before, after, and 1.5 h after
      exercise. Plasma LPS concentration after exercise increased by 71% (trial 1, p <
      0.05) and 21% (trial 2) in the NT group and by 92% (trial 1, p < 0.01) and 199%
      (trial 2, p < 0.01) in the IT group. Postintervention plasma LPS concentration
      was 35% lower before exercise (p < 0.05) and 47% lower during recovery (p < 0.01)
      in the IT than in the NT group. Anti-LPS IgM concentration during recovery was
      35% lower in the IT than in the NT group (p < 0.05). Plasma interleukin (IL)-6
      and tumor necrosis factor (TNF)-alpha concentration after exercise (IL-6, 3-7
      times, p < 0.01, and TNF-alpha, 33%, p < 0.01) and during recovery (IL-6, 2-4
      times, p < 0.05, and TNF-alpha, 30%, p < 0.01) were higher than at rest within
      each group. These data suggest that a short-term tolerable increase in training
      load may protect against developing endotoxemia during exercise in the heat.

PMID- 19767797
TI  - Effects of the self-contained breathing apparatus on left-ventricular function at
      rest and during graded exercise.
AB  - The purpose of this study was to examine the effects of the self-contained
      breathing apparatus (SCBA) on left-ventricular (LV) function at rest and during
      mild- to moderate-intensity exercise, using 2-dimensional echocardiography.
      Twenty-three healthy male volunteers exercised on a stair-climber at work rates
      equivalent to 50%, 60%, 70%, and 80% of peak oxygen consumption. Esophageal
      pressure LV diastolic and systolic cavity areas, and myocardial areas were
      acquired during the final minute of each stage of exercise. As expected, the
      esophageal pressure response during SCBA breathing revealed significantly lower
      (more negative) inspiratory pressures and higher (more positive) expiratory
      pressures and, consequently, higher pressure swings, than free breathing (FB).
      End-diastolic cavity area (EDCA) and end-systolic cavity area (ESCA) were lower
      with the SCBA than with FB. LV contractility was higher (p < 0.05) with the SCBA,
      which can partially be explained by decreases in end-systolic wall stress.
      Therefore, the SCBA was found to decrease LV preload during moderate-intensity
      exercise, but did not negatively affect stroke area because of a similar
      reduction in ESCA.

PMID- 19767798
TI  - Does habitual dietary intake influence myofiber hypertrophy in response to
      resistance training? A cluster analysis.
AB  - Although resistance exercise training (RT) is a common intervention to stimulate
      muscle protein synthesis and increase skeletal muscle mass, the optimal daily
      protein and total energy intakes sufficient to support RT-mediated muscle growth
      are as yet unclear. Further, the efficacy of RT varies widely among adults of all
      ages and whether this is attributable to interindividual differences in nutrition
      is not known. To determine if self-selected daily intake of macronutrients and
      specific components of dietary protein and fat are predictive of the magnitude of
      RT-mediated muscle growth, detailed 4-day dietary records were analyzed on 60
      subjects previously clustered (K-means cluster analysis) as non-, modest, and
      extreme responders (non, n = 16; mod, n = 29; xtr, n = 15), based on the
      magnitudes of change in vastus lateralis myofiber cross-sectional area following
      a 16-week, 3-day-per-week, high-intensity RT. Despite the marked contrast between
      60% myofiber hypertrophy in xtr and zero growth in non, we found no differences
      among response clusters in daily intakes of energy (mean +/- SEM: non 102 +/- 8;
      mod 111 +/- 6; xtr 109 +/- 5 kJ.kg-1.day-1), protein (non 0.97 +/- 0.08; mod 1.07
      +/- 0.07; xtr 1.05 +/- 0.06 g.kg-1.day-1), carbohydrate (non 3.02 +/- 0.24; mod
      3.18 +/- 0.20; xtr 3.14 +/- 0.17 g.kg-1.day-1), and fat (non 0.95 +/- 0.09; mod
      1.05 +/- 0.08; xtr 1.03 +/- 0.08 g.kg-1.day-1), which generally met or exceeded
      dietary recommendations. There were no cluster differences in intakes of branched
      chain amino acids known to stimulate muscle protein synthesis. Using the novel K
      means clustering approach, we conclude from this preliminary study that protein
      and energy intakes were sufficient to facilitate modest and extreme muscle growth
      during RT and intrinsic or extrinsic factors other than nutrient ingestion
      apparently impaired the anabolic response in nonresponders.

PMID- 19767799
TI  - Greater daily leisure time physical activity is associated with lower chronic
      disease risk in adults with spinal cord injury.
AB  - The objective of this study was to examine the relationship between leisure time
      physical activity (LTPA) and common risk factors for cardiovascular disease (CVD)
      and type 2 diabetes in community-dwelling adults with chronic spinal cord injury
      (SCI). LTPA was measured using the Physical Activity Recall Assessment for People
      with SCI in 76 men and women with chronic (> or =1 year) paraplegia or
      tetraplegia, living in or near Hamilton, Ontario. Body mass index (BMI), waist
      circumference, body composition (fat mass (FM) and fat-free mass (FFM)), blood
      pressure, and biochemical data were collected. Thirty-seven percent (n = 28
      participants) were inactive, reporting no LTPA whatsoever, and were compared with
      an equal-sized group consisting of the most active study participants (> or =25
      min of LTPA per day). After adjusting for significant covariates, BMI (18.7%),
      %FM (19.4%), and C-reactive protein (143%) were all lower, and %FFM was higher
      (7.2%), in active participants (all p < or = 0.05). Ten percent of active
      participants vs. 33% of inactive participants were insulin resistant (p = 0.03).
      Waist circumference (17.6%) and systolic blood pressure (15.3%) were lower in
      active vs. inactive participants with paraplegia (both p < or = 0.05), but not
      tetraplegia. In conclusion, greater daily LTPA is associated with lower levels of
      selected CVD and type 2 diabetes risk factors in individuals living with SCI.
      Whether this relationship translates into a lower incidence of these chronic
      diseases has yet to be determined.

PMID- 19767800
TI  - Dietary patterns associated with glycemic index and glycemic load among Alberta
      adolescents.
AB  - The purpose of this study was to assess the dietary glycemic index (GI) and
      glycemic load (GL) of adolescents, based on a Web-based 24-h recall, and to
      investigate dietary predictors of GI and GL. In addition, the relationship
      between GI and GL and weight status was examined. A Web-based 24-h recall was
      completed by 4936 adolescents, aged 9-17 years; macronutrient and food group
      intakes were assessed using the ESHA Food Processor, the Canadian Nutrient File,
      and Canada's Food Guide. Dietary GI and GL were calculated based on published GI
      values for foods. Students provided self-reported height and mass. Multiple
      regression models assessed the ability of food group choices and food behaviours
      to predict GI and GL. Mean GI was 55 for girls and 56 for boys. Mean GL was 128
      for girls and 168 for boys. Food group choices explained 26% of the variation in
      GI (p < 0.01) and 84% of the variation in GL (p < 0.01). The number of meals per
      day explained 10% (p < 0.01), and eating meals outside of the home accounted for
      2.5% (p < 0.01) of the variation in GL; however, these results disappeared when
      adjusted for total energy intake. The GI was positively correlated with body mass
      index in girls (r = 0.05, p = 0.02), and GL was significantly higher among
      nonoverweight boys than overweight boys. This study identified eating patterns
      related to daily GI and GL, and suggests certain dietary patterns that could have
      beneficial effects on health. It also showed that GI and GL were weakly related
      to weight status.

PMID- 19767801
TI  - Preinfection aerobic treadmill training improves resistance against Trypanosoma
      cruzi infection in mice.
AB  - Exercise performed before infections has been linked to improvement of the immune
      response against infections. The purpose of this study was to evaluate the
      influence of preinfection moderate-intensity treadmill training on acute
      Trypanosoma cruzi infection in mice. Ninety-nine female BALB/c mice were divided
      into 4 groups, as follows: training + infection (T+I) (n = 41); no training +
      infection (NT+I) (n = 38); training + no infection (T+NI) (n = 10); and no
      training + no infection (NT+NI) (n = 10). The exercise program for trained groups
      was carried out on a motorized treadmill for 8 weeks. Infected groups were
      inoculated with the Y strain of T. cruzi. Infectivity, prepatent period, patent
      period, parasitemia peak, mortality, survival time, weight, food intake, tumor
      necrosis factor-alpha serum levels, and peritoneal macrophage hydrogen peroxide
      production were evaluated. We found that preinfection training induced
      statistically significant reductions in parasitemia peak (p < 0.03) and weight
      loss (p < 0.04). However, no statistically significant differences were found for
      the other parameters evaluated when trained and nontrained infected groups were
      compared. We conclude that preinfection aerobic training induces some improvement
      in the immune response to T. cruzi infection in female BALB/c mice.

PMID- 19767802
TI  - Estimating leisure-time physical activity energy expenditure in the Canadian
      population: a comparison of 2 methods.
AB  - The purpose of this study was to determine the impact of 2 different calculation
      methods for total leisure-time physical activity energy expenditure (LTPAEE) and
      LTPAEE from different intensity activities on the classification of level of
      physical activity in the population. Nationally representative cross-sectional
      data from the Canadian Community Health Survey Cycle 4.1 (2007) were used for
      this study (N = 64, 397). LTPAEE was calculated using a metabolic equivalent
      (MET) value of 4.0 for all activities in the "other activity" category for method
      1 (currently employed by Statistics Canada) and using activity-specific MET
      values for method 2. The weighted prevalence and 95% confidence intervals of
      active (> or =3 kcal.kg-1.day-1 (kkd)), moderately active (1.5-2.9 kkd), and
      inactive (<1.5 kkd) were determined for each method by demographic
      characteristics. The agreement between the 2 methods was assessed overall, and
      for light, moderate, and vigorous activities. There was no difference between
      methods in the proportion classified as active, moderately active, or inactive
      for any of the subgroups studied and there was no difference in the distribution
      or mean LTPAEE between methods. However, assessment of the agreement showed a
      large number of outliers and a tendency to underestimate LTPAEE from light and
      vigorous activities while overestimating LTPAEE from moderate activities at the
      individual level. The results of this study should be considered when performing
      inferential statistics on the relationship between physical activity and health
      outcomes.

PMID- 19767803
TI  - The effect of an inverted body position on lower limb muscle force and
      activation.
AB  - Complete inversion of the body in a seated position may occur in exceptional
      circumstances such as in overturned vehicles and during military maneuvers, with
      direct consequences on health and fatalities. However, the physiological
      responses to this condition have not been published previously. The purpose of
      this study was to compare neuromuscular responses to upright and inverted seated
      positions. Sixteen subjects performed maximal voluntary contraction (MVC) and
      submaximal voluntary contraction knee extensions (25%, 50%, and 75% of MVC) under
      upright and inverted seated positions. Force, quadriceps activation as measured
      by the interpolated twitch technique, electromyographic (EMG) activity of the
      vastus lateralis, and semitendenosis and evoked contractile properties of the
      quadriceps were measured. Results demonstrated that MVC force (p = 0.01, 6.1%)
      and vastus lateralis EMG (p = 0.009, 29.6%) decreased in the inverted compared
      with the upright position. Instantaneous strength in the inverted position was
      19.3% lower than in the upright position (p = 0.005). Heart rate and diastolic
      and systolic blood pressures were 12.4%, 9.2%, and 10.7% lower (p < 0.0001),
      respectively, in the inverted position. In conclusion, a seated inverted position
      impaired MVC force and EMG activity, which could not be attributed to evoked
      contractile properties. The changes in heart rate and blood pressure may suggest
      inversion-induced alterations to the sympathetic nervous stimulation.

PMID- 19767804
TI  - The effect of a carbohydrate-caffeine sports drink on simulated golf performance.
AB  - A round of golf lasts approximately 4 h, during which time homeostasis could be
      challenged through either hypoglycemia or hypohydration. This might result in
      impaired motor skill or cognitive performance. Given the high cognitive demand of
      putting and the potential fatiguing effects from prolonged walking, the
      combination of a caffeine and carbohydrate drink could be beneficial in
      offsetting hypoglycemia and hypohydration. This study used a laboratory-simulated
      round of golf to examine the effect of an isotonic carbohydrate and caffeine
      sports drink on putting performance during a round of golf. After institutional
      ethics approval, 20 male golfers (mean +/- standard deviation: age 23 +/- 4
      years, stature 176.4 +/- 5.6 cm, mass 72.8 +/- 17.4 kg, handicap 15 +/- 4, daily
      caffeine consumption 157.3 +/- 47.2 mg) consumed either an isotonic sports drink
      containing caffeine (6.4 g carbohydrate and 16 mg caffeine per 100 mL) or a no
      energy, flavour-matched placebo drink in a double-blind, randomized, counter
      balanced crossover design . Drinks were consumed preround (5 mL.kg-1 body mass
      (BM)) and at holes 6 and 12 (2.5 mL.kg-1 BM). Participants therefore consumed 1.6
      mg.kg-1 BM of caffeine and 0.64 g.kg-1 BM of carbohydrate throughout the trial.
      Five and 2 m putting performance were assessed at each hole. Self-rated mood
      assessments were carried out every third hole. Putting performance over 5 m and 2
      m and self-rated scores for alertness and relaxation showed a main effect for
      drink (p < 0.05). Ratings of mental fatigue and tiredness significantly increased
      during the round (p < 0.001). In experienced golfers, the consumption of an
      isotonic carbohydrate sports drink containing caffeine prior to and during a
      round of golf improved putting performance and increased feelings of alertness.

PMID- 19767805
TI  - Sex alters impact of repeated bouts of sprint exercise on neuromuscular activity
      in trained athletes.
AB  - This study characterized the effect of sex on neuromuscular activity during
      repeated bouts of sprint exercise. Thirty-three healthy male and female athletes
      performed twenty 5-s cycle sprints separated by 25 s of rest. Mechanical work and
      integrated electromyograhs (iEMG) of 4 muscles of the dominant lower limb were
      calculated in every sprint. The iEMG signals from individual muscles were summed
      to represent overall electrical activity of these muscles (sum-iEMG).
      Neuromuscular efficiency (NME) was calculated as the ratio of mechanical work and
      sum-iEMG for every sprint. Arterial oxygen saturation was estimated (SpO2) with
      pulse oximetry throughout the protocol. The sprint-induced work decrement (18.9%
      vs. 29.6%; p < 0.05) and sum-iEMG reduction (11.4% vs. 19.4%; p < 0.05) were less
      for the women than for the men. However, the sprints decreased NME (10.1%; p <
      0.05) and SpO2 (3.4%; p < 0.05) without showing sex dimorphism. Changes in SpO2
      and sum-iEMG were strongly correlated in both sexes (men, R2 = 0.87; women, R2 =
      0.91; all p < 0.05), although the slope of this relationship differed (6.3 +/-
      2.9 vs. 3.8 +/- 1.6, respectively; p < 0.05). It is suggested that the sex
      difference in fatigue during repeated bouts of sprint exercise is not likely to
      be explained by a difference in muscle contractility impairment in men and women,
      but may be due to a sex difference in muscle recruitment strategy. We speculate
      that women would be less sensitive to arterial O2 desaturation than men, which
      may trigger lower neuromuscular adjustments to exhaustive exercise.

PMID- 19767806
TI  - Effects of ovariectomy and resistance training on MMP-2 activity in skeletal
      muscle.
AB  - Matrix metallopeptidases (MMPs) are crucial to the maintenance of healthy tissue.
      The aim of this study was to investigate MMP-2 activity in gastrocnemius, soleus,
      tibialis anterior (TA), and extensor digitorium longus (EDL) muscle after
      resistance training in ovariectomized rats. Wistar adult female rats were grouped
      into 7 groups (n = 10 per group): sedentary (Sed-Intact); ovariectomized
      sedentary (Sed-Ovx); pseudo-ovariectomized sedentary (Sed-Pseudo); acute exercise
      (AcuteEx-Intact); ovariectomized acute exercise (AcuteEx-Ovx); strength trained
      (ChronicEx-Intact); and ovariectomized strength trained (ChronicEx-Ovx). A 12
      week resistance training period, during which the animals climbed a 1.1-m
      vertical ladder with weights secured to their tails, was used. The sessions were
      performed once every 3 days, with 4-9 climbs and 8-12 dynamic movements per
      climb. The MMP-2 activity was analyzed by zymography. There was higher MMP-2
      activity in soleus muscle in the ChronicEx-Intact and ChronicEx-Ovx groups, and
      lower MMP-2 activity in the AcuteEx-Ovx group, compared with the Sed-Intact group
      (p < or =0.05). The Sed-Ovx and ChronicEx-Ovx groups presented lower MMP-2
      activity than the Sed-Intact group in TA. There was higher MMP-2 activity in
      AcuteEx-Intact and the AcuteEx-Ovx compared with the Sed-Intact and Sed-Ovx in
      TA, respectively (p < or = 0.05). In TA and EDL, training increased MMP-2
      activity in the Sed-Intact group. No statistically significant alterations were
      observed for gastrocnemius muscle. Strength training increases MMP-2 activity in
      soleus, TA, and EDL muscle, which may be important for muscle remodeling.
      Ovariectomy downregulates MMP-2 in TA and EDL, which may compromise muscle
      function.

PMID- 19767807
TI  - Are Canadians meeting the guidelines for moderate and vigorous leisure-time
      physical activity?
AB  - The purpose of this study was to determine the proportion of Canadian adults
      (aged 18-55 years) who met the guidelines for moderate and vigorous physical
      activity set out in Canada's Physical Activity Guide to Healthy Active Living.
      Leisure-time physical activity energy expenditure from moderate- and vigorous
      intensity activities was calculated using data from the National Population
      Health Surveys (1994-1998) and the Canadian Community Health Surveys (2001-2007).
      The prevalence was estimated for no leisure-time physical activity, meeting only
      the moderate guideline, meeting both the moderate and vigorous guidelines, and
      meeting the guidelines through a combination of moderate and vigorous activities.
      Logistic regression was used to determine the odds of meeting the guidelines by
      various demographic characteristics. The prevalence of no activity did not change
      appreciably over time, ranging from 6.5% to 10%, depending on the survey year.
      Reporting of no activity was more prevalent among older adults, those in lower
      income groups, and those with a body mass index (BMI) > or =30 kg.m-2. Overall,
      65% of adults met the guidelines for physical activity in 2007, which has
      increased from 54% in 1994-1995. Men, younger adults, those with a higher income,
      and those with a lower BMI more often met the guidelines. Among all subgroups,
      meeting the guidelines was most often accomplished through participation in
      moderate-intensity activities. These findings should be considered when designing
      and implementing public health interventions that promote participation in daily
      physical activity.

PMID- 19767808
TI  - Antioxidant status, oxidative stress, and damage in elite kayakers after 1 year
      of training and competition in 2 seasons.
AB  - The large volume of training performed by elite athletes throughout the season
      can translate into a chronic oxidative insult. To study the effects that
      chronically high training loads have on athletes' redox status, superoxide
      dismutase (SOD), glutathione reductase, glutathione peroxidase (GPx), and
      creatine kinase activities; total antioxidant status (TAS); and uric acid,
      retinol, alpha-tocopherol, alpha-carotene, beta-carotene, lycopene, lutein +
      zeaxanthin, vitamin C, thiobarbituric acid reactive substances (TBARS),
      interleukin-6, and cortisol levels were determined in 9 kayakers (6 men) in a
      competitive period during the first season (June, T1), and in precompetitive
      (March, T2) and competitive (June, T3) periods during the following season. TAS
      decreased from the first to the second season (T1 vs. T2, p < 0.001; T1 vs. T3, p
      < 0.001). TBARS (p = 0.024) decreased from T1 to T2. The alpha-tocopherol
      increase (p = 0.001) from T1 to T2 lost statistical significance after adjustment
      for total lipids (p = 0.243). GPx (p = 0.003) increased, while SOD (p < 0.001)
      and uric acid (p = 0.032) decreased from T2 to T3. Cortisol levels decreased
      significantly throughout the study (T1 vs. T2, p = 0.042; T2 vs. T3, p = 0.018;
      T1 vs. T3, p = 0.002). No significant differences were observed for any of the
      other parameters studied. Antioxidant status changed more within the same season
      than from one season to another. Redox markers should be monitored throughout the
      season to detect athletes at an increased oxidative risk.

PMID- 19767809
TI  - Age- and sex-associated differences in isokinetic knee muscle endurance between
      young children and adults.
AB  - The purpose of this study was to examine the age- and sex-associated differences
      of repeated isokinetic knee extension and flexion. Fifty one participants, 30
      young children (16 boys and 14 girls; aged 11 and 12 years) and 21 adults (9
      males and 12 females; aged 18-35 years), agreed to participate in the study.
      Isokinetic concentric peak knee extension (PET) and flexion (PFT) torque were
      measured using a calibrated Biodex System 3. Participants performed 4 concentric
      extension-flexion cycles with maximum effort; after a 2 min rest, 50 continuous
      concentric cycles were performed at 1.56 rad.s-1. Total work of the extensors
      (WKEX) and flexors (WKFL) for the complete 50 repetitions was recorded. Average
      peak torque and average work for the first and last 3 repetitions were calculated
      to represent the percentage decline in torque and work. There were no significant
      differences between groups in the peak torque generated during the pretrial and
      endurance task, suggesting that participants gave a maximal effort at the start
      of the endurance task. There was a significant interaction effect in the total
      work done for both extensors and flexors, with adult males producing the greatest
      amount of work (6622 and 3444 J, respectively). When total work was divided by
      body mass, there were no significant sex effects, only main effects for group.
      The percentage decline for PET (40% vs. 60%), PFT (50% vs. 65%), WKET (43% vs.
      61%), and WKFL (60% vs. 69%) demonstrated significant main effects for group,
      with greater fatigue in adults. We found no significant sex effect for fatigue.
      This study concludes that females do not resist fatigue from repeated isokinetic
      muscle actions to a greater extent than males, and that the greater fatigue in
      adults than in children is probably a product of greater initial torque
      production and work performed.

PMID- 19767810
TI  - Modeling age-related neuromuscular changes in humans.
AB  - With aging, motoneurons and muscle tissue undergo significant changes, which
      influence function in terms of strength, mobility, and overall independence.
      Mathematical modeling provides a practical method of studying the relationships
      among recruitment, rate-coding, and force output in motor units, and may be used
      to predict functional neuromuscular changes related to aging. For this study, the
      Heckman-Binder model was used to examine changes in human quadriceps motor units.
      Relationships among current input, firing frequency, and force output were
      defined for both a younger and an older individual. Included in the model were
      age-related effects associated with reduced muscle contractile speed; reduced
      muscle-fibre number, size, and specific tension; reduced gain of the frequency
      current relationship; decreased size of motoneurons; and altered motor unit
      remodeling. Adjustment of this model to reflect age-related changes resulted in a
      leftward shift of the force-frequency function, lower firing frequency for any
      given current injected into the motoneuron, and a reduction in maximal force
      output. The model suggests that older individuals are capable of reaching force
      levels up to approximately 50% of those attained by younger individuals, with
      relatively similar or even slightly lower levels of current input. This could
      mean that the sense of effort and the contribution of factors other than degree
      of effort from afferent inputs to the pool, including conscious supraspinal
      centres, might be different in the older adult.

PMID- 19767811
TI  - Effects of eccentric treadmill exercise on inflammatory gene expression in human
      skeletal muscle.
AB  - The present study examined the skeletal muscle expression of several genes
      related to the inflammatory process before and after a bout of downhill running.
      Twenty-nine males between the ages of 18 and 35 years performed a 45-min downhill
      (-17.5%) treadmill protocol at 60% of maximal oxygen consumption. Venous bloods
      samples and muscle biopsy samples from the vastus lateralis were donated prior to
      and at 3-h and 24-h postexercise, along with ratings of perceived muscle
      soreness. Serum creatine kinase (CK) was determined, as was skeletal muscle gene
      expression of interleukin (IL)-6, IL-8, IL-12 (p35), tumor necrosis factor-alpha
      (TNF-alpha), IL-1beta, cyclooxygenase 2 (COX2), and nuclear factor kappa B (NFkB)
      (p105/p50). Gene expression was analyzed using RT-PCR and compared with a
      standard housekeeping gene (beta-actin). Data were analyzed for statistical
      differences using multivariate analysis of variance with univariate follow-up. In
      addition, Pearson correlations were conducted to determine if any significant
      relationship exists between any of these transcripts and both CK and muscle
      soreness. Significant (p < 0.05) up-regulations in IL-6, IL-8, and COX2 mRNA
      expression were observed compared with baseline, whereas no significant changes
      for IL-12, IL-1beta, TNF-alpha, or NFkB were noted. Significant increases in IL-6
      mRNA were observed at 3 h (p < 0.001) and 24 h (p = 0.043), whereas significant
      increases in IL-8 (p = 0.001) and COX2 (p = 0.046) mRNA were observed at 3-h
      postexercise. In addition, muscle soreness was significantly correlated with IL-8
      at 24 h (r = -0.370; p = 0.048), whereas CK was significantly related to NFkB at
      baseline (r = -0.460; p = 0.012). These data indicate that increases in the mRNA
      expression of IL-6, IL-8, and COX2 occur in the vastus lateralis as a result of
      damaging eccentric exercise in young, recreationally trained males. Further, it
      appears that IL-8 transcription may play some role in inhibiting postexercise
      muscle soreness, possibly through regulation of angiogenesis.

PMID- 19767812
TI  - Relationship of blood pressure, behavioral mood state, and physical activity
      following caffeine ingestion in younger and older women.
AB  - The purpose of this study was to examine the age-related differences in blood
      pressure, heart rate, and behavioral mood state after caffeine ingestion in
      younger and older women. Using a placebo-controlled, double-blind design, 10
      younger (Y; 18-22 years) and 10 older (O; 50-67 years) healthy women who were
      moderate consumers of caffeine (self-reported mean intake: Y, 139 +/- 152 mg.day
      1; O, 204 +/- 101 mg.day-1) were investigated. All volunteers were characterized
      for fasting plasma glucose, insulin, free-fatty acids and caffeine levels, body
      composition, cardiovascular fitness, physical activity, and energy intake. Before
      and after placebo and caffeine ingestion (5 mg.kg-1 fat-free mass; approximately
      208-270 mg) test days, the following variables were measured in all subjects:
      plasma caffeine levels, heart rate, blood pressure, and behavioral mood state.
      Results showed that, following caffeine ingestion: (i) both systolic and
      diastolic blood pressure (SBP and DBP, respectively) increased significantly (p <
      0.05) in the older women (SBP, 128.4 +/- 14.2 vs. 132.1 +/- 13.0 mm Hg (3%); DBP,
      80.2 +/- 6.9 vs. 83.4 +/- 7.5 mm Hg (4%), whereas only DBP increased in the
      younger women (67.1 +/- 4.7 vs. 69.9 +/- 5.4 mm Hg (4.2%); p < 0.05); (ii) heart
      rate decreased significantly (Y, 59.2 +/- 8.7 to 53.9 +/- 10.6 beats.min-1 (p <
      0.05); O, 61.9 +/- 9.2 to 59.2 +/- 8.4 beats.min-1 (p < 0.05)) in both groups;
      and (iii) self-reported feelings of tension and vigor increased and feelings of
      fatigue decreased (p < 0.05) in younger women, whereas depression decreased (p <
      or = 0.05) in older women. Self-reported level of physical activity was inversely
      related to change in DBP following caffeine ingestion in younger women. In
      conclusion, blood pressure response is augmented and subjective feelings of
      behavioral mood state are attenuated to a greater degree in older than in younger
      women following acute caffeine ingestion. Less physically active younger women
      are more vulnerable to the pressor response to caffeine than more active younger
      women. It should be noted that these findings are limited to moderate consumers
      of caffeine who abstained for 48 h prior to testing, and who ingested caffeine in
      pill form (approximately 240 mg).

PMID- 19767813
TI  - Physiological correlates of 2-mile run performance as determined using a novel on
      demand treadmill.
AB  - The purpose of this study was to assess the reproducibility of an on-demand
      motorised treadmill to measure 2-mile (3.2 km) race performance and to examine
      the physiological variables that best predict this free-running performance in
      active men. Twelve men (mean (SD): age, 28 (9) years; stature, 1.79 (0.05) m;
      body mass, 72 (9) kg) completed the study in which maximum oxygen uptake (VO2
      max), running economy, and running speedin the abstract section. They appear in
      the rest of the paper.), running economy, and running speed at VO2 max (vVO2
      max), lactate threshold (vLT), and 4 mmol.L-1 fixed blood lactate concentration
      (v4) were measured. Subsequently, the maximal lactate steady state (MLSS) was
      identified using a series of 30-min treadmill runs. Finally, each participant
      completed a 2-mile running performance trial on 2 separate occasions, using an on
      demand treadmill that adjusts belt speed according to the participant's position
      on the moving belt. The average 2-mile run speed was 15.7 (SD, 1.9) km.h-1, with
      small individual differences between repeat-performance trials (intraclass
      correlation coefficient = 0.99, 95% CI 0.953 to 0.996; standard error of
      measurement as coefficient of variation = 1.5%, 95% CI 1.0% to 2.5%). Bivariate
      regression analyses identified VO2 max, vVO2 max, VO2 (mL.kg-1.min-1) at MLSS,
      vLT, v4, and velocity at MLSS (vMLSS) as the strongest individual predictor
      variables (r2 = 0.69 to 0.87; standard error of the estimate = 1.08 to 0.72 km.h
      1) for 2-mile running performance. The vLT and vMLSS explained 85% and 87% of the
      variance in running performance, respectively, suggesting that there is
      considerable shared variance between these parameters. In conclusion, the on
      demand treadmill system provided a reliable measure of distance running
      performance. Both vLT and vMLSS were strong predictors of 2-mile running
      performance, with vMLSS explaining marginally more of the variance.

PMID- 19767815
TI  - Postexercise rehydration in man: the effects of carbohydrate content and
      osmolality of drinks ingested ad libitum.
AB  - The effectiveness of different carbohydrate solutions in restoring fluid balance
      in situations of voluntary fluid intake has not been examined previously. The
      effect of the carbohydrate content of drinks ingested after exercise was examined
      in 6 males and 3 females previously dehydrated by 1.99 +/- 0.07% of body mass via
      intermittent exercise in the heat. Beginning 30 min after the cessation of
      exercise, subjects drank ad libitum for a period of 120 min. Drinks contained 31
      mmol.L-1 Na+ as NaCl and either 0%, 2%, or 10% glucose with mean +/- SD
      osmolalities of 74 +/- 1, 188 +/- 3, and 654 +/- 4 mosm.kg-1, respectively. Blood
      and urine samples were collected before and after exercise, midway through
      rehydration, and throughout a 5 h recovery period. Total fluid intake was not
      different among trials (0%: 2258 +/- 519 mL; 2%: 2539 +/- 436 mL; 10%: 2173 +/-
      252 mL; p = 0.173). Urine output was also not different among trials (p = 0.160).
      No differences among trials were observed in net fluid balance or in the fraction
      of the ingested drink retained. In conclusion, in situations of voluntary fluid
      intake, hypertonic carbohydrate-electrolyte solutions are as effective as
      hypotonic carbohydrate-electrolyte solutions at restoring whole-body fluid
      balance.

PMID- 19767814
TI  - Systemic indices of skeletal muscle damage and recovery of muscle function after
      exercise: effect of combined carbohydrate-protein ingestion.
AB  - Previous studies indicate that exercise-induced muscle damage may be attenuated
      when protein is included in a carbohydrate recovery supplement. This study was
      designed to examine systemic indices of muscle damage, inflammation, and recovery
      of muscle function, following strenuous exercise, with ingestion of either
      carbohydrate alone or a carbohydrate-protein mixture. Seventeen highly trained
      volunteers participated in 2 trials in a randomized order, separated by
      approximately 9 weeks. Each trial involved 90 min of intermittent shuttle
      running, either with ingestion of a 9% sucrose solution during and for 4 h after
      (1.2 g.kg-1 body mass.h-1) or with the same solution plus 3% whey protein isolate
      (0.4 g.kg-1 body mass.h-1). Blood was sampled throughout and 24 h after each
      trial to determinate the systemic indices of muscle damage and inflammation. An
      isokinetic dynamometer was used to establish reliable baseline measurements of
      peak isometric torque for knee and hip flexors and extensors, which were then
      followed-up at 4-, 24-, 48-, and 168-h postexercise. The exercise protocol
      resulted in significantly elevated variables indicative of muscle damage and
      inflammation, while peak isometric torque was immediately reduced by 10%-20%
      relative to baseline, across all muscle groups tested. However, none of these
      responses varied in magnitude or time-course between the treatments, or between
      participants' first and second trials. The addition of whey protein isolate to a
      dietary carbohydrate supplement ingested during and for 4 h following strenuous
      exercise did not attenuate systemic indices of muscle damage or inflammation, nor
      did it restore muscle function more rapidly than when the carbohydrate fraction
      was ingested alone.

PMID- 19767816
TI  - Physical activity of children in family child care.
AB  - Physical activity was monitored for 65 boys and girls, during family child care,
      using accelerometry. Average accelerometer wear time was 7.0 h (SD = 0.83), and
      average counts per epoch were 104.6 (SD = 31.6). Mean minutes per hour of
      moderate-vigorous physical activity and sedentary behaviour were 1.76 min (SD =
      0.90) and 39.49 min (SD = 4.50), respectively. The very low levels of moderate
      vigorous physical activity suggest that the young children in this study may be
      insufficiently active during child care.

PMID- 19767819
TI  - Calreticulin and focal-contact-dependent adhesion.
AB  - Cell adhesion is regulated by a variety of Ca2+-regulated pathways that depend on
      Ca2+-binding proteins. One such protein is calreticulin, an ER-resident protein.
      Calreticulin signalling from within the ER can affect processes outside the ER,
      such as expression of several adhesion-related genes, most notably vinculin and
      fibronectin. In addition, changes in the expression level of calreticulin
      strongly affect tyrosine phosphorylation of cellular proteins, which is known to
      affect many adhesion-related functions. While calreticulin has been localized to
      cellular compartments other than the ER, it appears that only the ER-resident
      calreticulin affects focal-contact-dependent adhesion. In contrast, calreticulin
      residing outside the ER may be involved in contact disassembly and other adhesion
      phenomena. Here, we review the role of calreticulin in focal contact initiation,
      stabilization, and turnover. We propose that calreticulin may regulate cell
      substratum adhesion by participating in an "ER-to-nucleus" signalling and in
      parallel "ER-to-cell surface" signalling based on posttranslational events.

PMID- 19767820
TI  - Absence of the major light-harvesting antenna proteins alters the redox
      properties of photosystem II reaction centres in the chlorina F2 mutant of
      barley.
AB  - Although the chlorina F2 mutant of barley specifically exhibits reduced levels of
      the major light-harvesting polypeptides associated with photosystem II (PSII),
      thermoluminescence measurements of photosystem reaction centre photochemistry
      revealed that S2/S3QB- charge recombinations were shifted to lower temperatures,
      while the characteristic peak of S2QA- charge recombinations was shifted to
      higher temperatures compared with wild-type (WT) barley. Thus, we show that the
      absence of the major light-harvesting polypeptides affects the redox properties
      of PSII reaction centres. Radiolabeling studies in vivo and in vitro with
      [32P]orthophosphate or [gamma-32P]ATP, respectively, demonstrated that the D1
      PSII reaction centre polypeptide is phosphorylated in both the WT and the F2
      mutant. In contrast with the radiolabeling results, phosphorylation of D1 and
      other PSII proteins, although detected in WT barley, was ambiguous in the F2
      mutant when the phosphothreonine antibody method of detection was used. Thus,
      caution must be exercised in the use of commercially available phosphothreonine
      antibodies to estimate thylakoid polypeptide phosphorylation. Furthermore, in
      membrano, the D1 polypeptide of the F2 mutant was less susceptible to trypsin
      treatment than that of WT barley. The role of the light-harvesting complex in
      modulating the structure and function of the D1 polypeptide of PSII reaction
      centers is discussed.

PMID- 19767821
TI  - Coordinate Galpha13 and Wnt6-beta-catenin signaling in F9 embryonal carcinoma
      cells is required for primitive endoderm differentiation.
AB  - The mouse F9 embryonal carcinoma cell line is ideally suited to study the
      epithelial-to-mesenchymal transition accompanying the differentiation of
      primitive to parietal extraembryonic endoderm. In F9 cells, the application of
      exogenous agents including retinoic acid or activation of signal transduction
      cascades downstream of G-proteins triggers widespread changes in gene expression
      and leads to the formation of primitive endoderm. The epithelial-to-mesenchymal
      transition is completed and parietal endoderm develops as of result of increasing
      PKA activity in primitive endoderm cells. Expression of a constitutively active
      form of Galpha13(Q226L) is sufficient to induce F9 cells into parietal endoderm
      and a model is emerging that a signaling axis linking G-protein signaling to RhoA
      and the ERM protein moesin is required for differentiation. In this study, we
      found that expression of either p115RhoGEF or a constitutively active, GTPase
      deficient form of RhoA(L63) promoted primitive, but not parietal, endoderm
      formation. The overexpression of Galpha13(Q226L) or p115RhoGEF, but not Rho(L63),
      caused beta-catenin to translocate to the nucleus. Surprisingly, the stimulation
      of the Wnt-beta-catenin pathway was accompanied by nuclear beta-catenin and
      primitive endoderm formation, even when a dominant negative was used to block the
      signaling axis at the level of p115RhoGEF or when ROCK activity was inhibited
      using the pharmacological agent Y-27632. Together, results indicate that the
      coordinate signaling by two independent pathways, one involving canonical Wnt
      beta-catenin activation of target genes and the other with Galpha13 signaling to
      ERM proteins to modulate cytoarchitectural changes, is required during the
      retinoic acid induced differentiation of F9 cells to primitive endoderm.

PMID- 19767822
TI  - Involvement of a disintegrin and metalloproteinase 10 and 17 in shedding of tumor
      necrosis factor-alpha.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is initially synthesized as a membrane
      bound protein and converted into a soluble form by proteolytic cleavage. Although
      a disintegrin and metalloproteinase 17 (ADAM17) is considered to be the primary
      sheddase for TNF-alpha, it is not known whether ADAM17 is solely responsible for
      that process in any type of cells. To identify the TNF-alpha sheddase(s) in
      varieties of cells, we performed experiments using a unique screening system and
      observed that ADAM9, ADAM10, ADAM17, and ADAM19 were capable of cleaving TNF
      alpha. We then performed RNA interference experiments and confirmed that ADAM10
      and ADAM17 were in fact involved in TNF-alpha shedding in 293A cells. In mouse
      macrophages, ADAM17 was confirmed to be the primary sheddase, but the involvement
      of ADAM10 was also demonstrated. In NIH3T3 cells, ADAM10 could be more important
      in the shedding than ADAM17. In mouse vascular endothelial cell line UVfemale2,
      ADAM10 and ADAM17 were equally involved in TNF-alpha shedding, whereas ADAM17 was
      a major sheddase in human osteoarthritic chondrocytes. From these observations
      and others, we concluded that both ADAM10 and ADAM17 can be a TNF-alpha sheddase
      and that their significance could be determined by their expression levels and
      the abundance of tissue inhibitor of metalloproteinases.

PMID- 19767823
TI  - Contribution of bone marrow mesenchymal stem cells to porcine hepatocyte culture
      in vitro.
AB  - One of the greatest challenges in the attempt to create functional bioartificial
      liver designs is the maintenance of porcine hepatocyte differentiated functions
      in vitro. Co-cultivation of hepatocytes with nonparenchymal cells may be
      beneficial for optimizing cell functions via mimicry of physiological
      microenvironment. However, the underlying mechanisms remain to be elucidated. An
      equal number of freshly isolated porcine hepatocytes and purified bone marrow
      mesenchymal stem cells (MSCS) was randomly co-cultured and the morphological and
      functional changes of heterotypic interactions were characterized. Furthermore,
      contributions of soluble factors involved in the separated co-culture system were
      evaluated. The purity of the third-passage MSCS and primary hepatocytes was more
      than 90% and 99%, respectively. Hepatocyte viability was greater than 95%. A
      rapid attachment and self-organization of three-dimensional hepatocyte spheroids
      were encouraged, which was due to the supporting MSCS of high motility. The
      elevated induction of both albumin production and urea synthesis was achieved in
      co-culture (P < 0.05). Data from semipermeable membrane cultures suggested that
      interleukin-6 is one of the key stimulators in hepatic functional enhancement.
      These results demonstrate for the first time that soluble factors have beneficial
      effects on the preservation of hepatic morphology and functionality in the co
      culture of hepatocytes with MSCS in vitro, which could represent a promising tool
      for tissue engineering, cell biology, and bioartificial liver devices.

PMID- 19767824
TI  - Cadmium attenuates bradykinin-driven nitric oxide production by interplaying with
      the localization pattern of endothelial nitric oxide synthase.
AB  - Cadmium, a ubiquitous heavy metal, interferes with endothelial functions and
      angiogenesis. Bradykinin is a Ca-mobilizing soluble peptide that acts via nitric
      oxide to promote vasodilation and capillary permeability. The objective of the
      present study was to explore the Cd implications in bradykinin-dependent
      endothelial functions. An egg yolk angiogenesis model was employed to evaluate
      the effect of Cd on bradykinin-induced angiogenesis. The results demonstrate that
      100 nmol/L Cd attenuated bradykinin-dependent angiogenesis. The results of the in
      vitro wound healing and tube formation assays by using EAhy 926, a transformed
      endothelial cell line, suggest that Cd blocked bradykinin-mediated endothelial
      migration and tube formation by 38% and 67%, respectively, while nitric oxide
      supplementation could reverse the effect of Cd on bradykinin-induced endothelial
      migration by 94%. The detection of nitric oxide by using a DAF-2DA fluorescent
      probe, Griess assay, and ultrasensitive electrode suggests that Cd blocked
      bradykinin-induced nitric oxide production. Fluorescence imaging of eNOS-GFP
      transfected endothelial cells, immunofluorescence, and Western blot studies of Cd
      and bradykinin-treated cells show that Cd interfered with the localization
      pattern of eNOS, which possibly attenuates nitric oxide production in part.
      Additionally, Ca imaging of Cd- and bradykinin-treated cells suggests that Cd
      blocked bradykinin-dependent Ca influx into the cells, thus partially blocking Ca
      dependent nitric oxide production in endothelial cells. The results of this study
      conclude that Cd blunted the effect of bradykinin by interfering with the Ca
      associated NOS activity specifically by impeding subcellular trafficking of eNOS.

PMID- 19767825
TI  - Interaction of tRNA with antitumor polyamine analogues.
AB  - We studied the interaction between tRNA and three polyamine analogues (1,11
      diamino-4,8-diazaundecane.4HCl (333), 3,7,11,15-tetrazaheptadecane.4HCl (BE-333),
      and 3,7,11,15,19-pentazahenicosane.5HCl (BE-3333)) using FTIR, UV-visible, and CD
      spectroscopic methods. Spectroscopic evidence showed that polyamine analogues
      bound tRNA via guanine N7, adenine, uracil O2, and the backbone phosphate (PO2-)
      groups, while the most reactive sites for biogenic polyamines were guanine N7/O6,
      adenine N7, uracil O2, and sugar 2'-OH groups as well as the backbone phosphate
      group. The binding constants of polyamine analogue-tRNA recognition were lower
      than those of the biogenic polyamine-tRNA complexes, with K333 = 2.8 (+/-0.5) x
      10(4), K(BE-333) = 3.7 (+/-0.7) x 10(4), K(BE-3333) = 4.0 (+/-0.9) x 10(4),
      K(spm) = 8.7 (+/-0.9) x 10(5), K(spd) = 6.1 (+/-0.7) x 10(5), and K(put) = 1.0
      (+/-0.3) x 10(5) mol/L. tRNA remained in the A-family conformation; however, it
      aggregated at high polyamine analogue concentrations.

PMID- 19767826
TI  - Probing Alzheimer amyloid peptide aggregation using a cell-free fluorescent
      protein refolding method.
AB  - Fibrillation of the Alzheimer beta-amyloid peptide (Abeta) and (or) formation of
      toxic oligomers are key pathological events in Alzheimer's disease. Several
      strategies have been introduced to identify small molecule aggregation
      inhibitors, and based on these methods, a number of aggregation inhibitors have
      been identified. However, most of these methods use chemically synthesized
      Abeta42 peptides, which are difficult to maintain in a monomeric state at neutral
      pH where anti-aggregation screening is usually carried out. We have developed a
      cell-free Abeta42 aggregation assay based on fluorescence protein refolding. This
      assay utilizes nanomolar concentrations of protein. We genetically fused Abeta42
      to the N-terminus of vYFP, a variant of of GFP, and expressed and purified the
      folded fusion protein. The refolding efficiency of Abeta42-vYFP fusion was
      inversely correlated with the solubility of Abeta42. Using fluorescence to
      monitor refolding of Abeta42-vYFP, we confirmed that Zn2+ binds to Abeta42 and
      increases its aggregation. The IC50 value estimated for Zn binding is 3.03 +/-
      0.65 micromol/L. We also show that this technique is capable of monitoring the
      aggregation of chemically synthesized Abeta42.

PMID- 19767827
TI  - Exendin-4 exerts its effects through the NGF/p75NTR system in diabetic mouse
      pancreas.
AB  - Glucagon-like peptide-1 (GLP-1) ameliorates the symptoms of diabetes through
      stimulation of insulin secretion. We have investigated the possible components of
      cellular mechanism triggered by exendin-4, a potent GLP-1 receptor agonist, in
      streptozotocin (STZ) induced diabetic mice pancreas. BALB/c male mice were
      divided into four groups for this investigation. The first group was given
      citrate buffer only, the second group was administered exendin-4 alone, the third
      group received STZ, and the fourth group was given both STZ and exendin-4.
      Exendin-4 (3 microg/kg) was administered by daily subcutaneous injection for 30
      days after the animals were rendered diabetic by administration of STZ (200
      mg/kg). With exendin-4 treatment on diabetic mice, the following results were
      noted: (i) exendin-4 suppressed the increase in plasma glucose and inhibited
      somatostatin expression induced by STZ, (ii) reduction of insulin prevalence was
      inhibited, while expression of p75 neurotrophin receptor (p75NTR), pancreatic
      nerve growth factor (NGF), and NGF-positive islet cell prevalence increased,
      (iii) there were no alterations in the severity of proliferated cell nuclear
      antigen positive or apoptotic beta cells in pancreatic islets, and (iv)
      pancreatic catalase, glutathione peroxidase, and superoxide dismutase activities
      significantly increased. In conclusion, these data suggest that exendin-4 might
      exert its actions through the NGF/p75NTR system and decrease somatostatin
      expression.

PMID- 19767828
TI  - Novel role for the Saccharomyces cerevisiae oligopeptide transporter Opt2 in drug
      detoxification.
AB  - Saccharomyces cerevisiae Opt2 is a member of the oligopeptide transporter family
      that was initially identified to transport tetra- and pentapeptides. Mutants
      deleted for the OPT2 gene exhibit no growth defects under normal culture
      conditions. We identified OPT2 from a high-throughput screen that when deleted
      results in mutants that displayed sensitivity to the anticancer agent bleomycin.
      The opt2Delta mutant was also reisolated in two additional genome-wide screens
      designed to identify mutants that are sensitive to the immunosuppressant
      rapamycin and the divalent metal ion zinc. However, the role of Opt2 in
      protecting cells against these agents was not investigated. Herein, we show that
      opt2Delta mutants are also sensitive to a wide variety of toxic agents that are
      typically detoxified by the vacuoles. Mutants lacking two other related
      oligopeptide transporters, Opt1 and Ygl114w, showed no significant sensitivities
      to these drugs, indicating a specific role for Opt2 in drug detoxification. The
      sensitivities of the opt2Delta mutants were not related to an increased drug
      uptake but rather to the presence of several small vesicles instead of a
      functional large vacuole. We propose that Opt2 has a novel function involving the
      fusion of vesicles to form a mature vacuole.

PMID- 19767829
TI  - Cysteine engineering of actin self-assembly interfaces.
AB  - The Holmes model of filamentous actin (F-actin) and recent structural studies
      suggest specific atomic interactions between F-actin subunits. We tested these
      interactions through a cysteine-engineering approach with the goal of inhibiting
      filament formation by introducing chemical groups at sites important for
      polymerization. We substituted surface amino acids on the actin molecule with
      cysteine residues and tested the effect of producing these actin mutant proteins
      in a yeast expression system. The intrinsic folding and polymerization
      characteristics of the cysteine-engineered actin proteins were measured. The
      effect of chemical modification of the introduced cysteine residues on the
      polymerization of the actin mutant proteins was also examined. Modification of
      cysteine residues with large hydrophobic reagents resulted in polymerization
      inhibition. We examined the finding that the D288C actin protein does not
      polymerize under oxidizing conditions and forms protein aggregates when magnesium
      and EGTA are present. Chemical crosslinking experiments revealed the presence of
      a lower dimer when only D288C actin was present. When both D288C and A204C actin
      were present, crosslinking experiments support the proximity of Asp288 on the
      barbed end of one subunit to Ala204 on the pointed end of a neighboring subunit
      in the Holmes model of F-actin.

PMID- 19767830
TI  - Glycosaminoglycan chains from alpha5beta1 integrin are involved in fibronectin
      dependent cell migration.
AB  - Alpha5beta1 integrin from both wild-type CHO cells (CHO-K1) and deficient in
      proteoglycan biosynthesis (CHO-745) is post-translationally modified by
      glycosaminoglycan chains. We demonstrated this using [35S]sulfate metabolic
      labeling of the cells, enzymatic degradation, immunoprecipitation reaction with
      monoclonal antibody, fluorescence microscopy, and flow cytometry. The alpha5beta1
      integrin heterodimer is a hybrid proteoglycan containing both chondroitin and
      heparan sulfate chains. Xyloside inhibition of sulfate incorporation into
      alpha5beta1 integrin also supports that integrin is a proteoglycan. Also, cells
      grown with xyloside adhered on fibronectin with no alteration in alpha5beta1
      integrin expression. However, haptotactic motility on fibronectin declined in
      cells grown with xyloside or chlorate as compared with controls. Thus,
      alpha5beta1 integrin is a proteoglycan and the glycosaminoglycan chains of the
      integrin influence cell motility on fibronectin. Similar glycosylation of
      alpha5beta1 integrin was observed in other normal and malignant cells, suggesting
      that this modification is conserved and important in the function of this
      integrin. Therefore, these glycosaminoglycan chains of alpha5beta1 integrin are
      involved in cellular migration on fibronectin.

PMID- 19767831
TI  - Labeling and imaging of GLUT4 in live L6 cells with quantum dots.
AB  - GLUT4 is sequestered in intracellular storage compartments in a basal state and
      is rapidly translocated to the cell surface in response to insulin stimulation.
      Regulation of GLUT4 distribution is key for maintaining whole-body glucose
      homeostasis. To investigate the complicated intracellular movement of GLUT4
      vesicles and their interactions with organelles in detail, new probes suitable
      for long-term tracking of cellular events are required. In this study, we
      introduce for the first time quantum dots (QDs) as a superior probe into the
      research of the mechanisms of GLUT4 translocation. QDs are light-emitting
      semiconductor nanoparticles with unique optical and spectroscopic properties,
      such as broad absorption, narrow and tunable emission, resistance to
      photobleaching, strong luminescence, and long luminescent lifetimes. Owing to
      their remarkable photophysical properties and relatively small size, QDs are
      emerging as an alternative to conventional dyes for fluorescence-based
      applications. We have developed a procedure for labeling and imaging GLUT4 in
      live cells with streptavidin-conjugated quantum dot (QD-SA) and demonstrated that
      QDs contained in cytoplasm have no obvious negative influence on L6 cells. This
      study provides a sensitive, nontoxic, long-term imaging platform for observing
      the dynamics and regulated characteristics of GLUT4 transport.

PMID- 19767832
TI  - Comparative quantification of Campylobacter jejuni from environmental samples
      using traditional and molecular biological techniques.
AB  - Campylobacter jejuni is one of the most common causes of gastroenteritis in the
      world. Given the potential risks to human, animal, and environmental health, the
      development and optimization of methods to quantify this important pathogen in
      environmental samples is essential. Two of the most commonly used methods for
      quantifying C. jejuni are selective plate counting and quantitative real-time PCR
      (qPCR). Unfortunately, little comparative research has been performed to evaluate
      the accuracy of these methods for quantification of C. jejuni in aqueous and
      solid matricies. In this study, the limit of detection and the level of
      resolution obtained using these 2 methods was evaluated for C. jejuni and
      compared with that of the common indicator organism Escherichia coli. The use of
      selective plate count media for quantification of C. jejuni resulted in a 0.7-1.2
      log underestimation of cell concentrations, compared with qPCR in both water and
      column leachate samples, whereas E. coli concentrations were found to be similar
      with either technique. For C. jejuni, only the qPCR assay accurately measured 2
      fold changes in cell concentrations in water samples, whereas concentrations of
      E. coli were accurately measured regardless of method. Based on these data, qPCR
      assays were found to be more accurate than selective plate counts for
      quantification of C. jejuni from environmental samples.

PMID- 19767833
TI  - Bifidobacterial survival in surface water and implications for microbial source
      tracking.
AB  - Bifidobacteria are common in the intestines of humans and other animals. Sorbitol
      fermenting Bifidobacteria (SFB) are associated with human faecal pollution. The
      ratio of total Bifidobacteria (TB) to SFB has been proposed to be a means for
      determining the source (human or animal) of faecal pollution. In this study, SFB
      were detected in all sewage samples (n = 39) and in 42% of samples of animal
      origin (n = 24): pig (5/6 positive), poultry (4/8), horse (1/4), and cow (0/6).
      The TB:SFB ratio was significantly higher in animal samples than in sewage
      samples (p < 0.01), with the exception of stored poultry manure, which had ratios
      (1.4-11) similar to the sewage samples (1-17). The lowest ratio in the other
      animal samples was 40 (pig). The TB:SFB ratio in sewage remained stable over time
      in surface water, and it may be a useful screening tool to determine the source
      of faecal pollution in surface water. Bifidobacteria died off in a log linear
      manner at 4 and 22 degrees C, with rates of disappearance of 0.16 and 0.58
      log(days-1), respectively. Faecal coliforms (FC) disappeared more slowly (0.09
      and 0.43 log(days-1), respectively). The FC:SFB ratio proved to be an inadequate
      tool for determining the age of sewage pollution.

PMID- 19767834
TI  - Lactobacillus casei: influence on the innate immune response and haemostatic
      alterations in a liver-injury model.
AB  - Lactobacilllus casei CRL 431 has the ability to modulate the local and systemic
      immune responses, which are significantly involved in liver injury caused by
      hepatotoxins. This work was conducted to determine whether L. casei has a
      preventive effect on the hepatic damage undergone during an acute liver injury
      (ALI). METHODS: ALI was induced by an intraperitoneal injection of d
      galactosamine (D-Gal). Different groups of mice received 1x 109 L. casei
      cells/day/mouse for 2 days before D-Gal injection. Blood and liver samples were
      obtained 0, 6, 12, and 24 h after D-Gal administration. RESULTS: D-Gal induced
      increases in serum aminotransferases, reduced the number of blood leukocytes,
      enhanced neutrophil myeloperoxidase activity, increased dead cells, and altered
      prothrombin time and plasma fibrinogen levels. The preventive treatment with L.
      casei for 2 days modulated the innate immune response. This effect was shown by
      the earlier normalization of white blood cell counts, myeloperoxidase activity
      and aminotransferases levels. However, the haemostatic parameters were only
      partially recovered. The favourable effects obtained could be due to the capacity
      of L. casei to moderate the inflammatory response at the site of the injury with
      less damage to liver tissue.

PMID- 19767835
TI  - Induction of Pseudomonas aeruginosa fhp and fhpR by reactive oxygen species.
AB  - In Pseudomonas aeruginosa, flavohemoglobin (Fhp) and its cognate regulator FhpR
      (PA2665) form a protective regulatory circuit, which responds to reactive
      nitrogen species and is also capable of protecting cells against nitrosative
      stress. Recently, it has been shown that the expression of the fhp promoter is
      regulated not only by FhpR, but also by two new regulators, PA0779 and PA3697. It
      has also been suggested that the bacterial flavohemoglobins (flavoHbs) could play
      a crucial role in the protection of cells against reactive oxygen species (ROS).
      Therefore, the role and function of the Fhp/FhpR system during oxidative stress
      were studied by assessing the viability and membrane integrity of P. aeruginosa
      cells and by analyzing the promoter activities of fhp and fhpR upon exposure to
      paraquat, hydrogen peroxide, and tert-butyl hydroperoxide, under both aerobic and
      low-oxygen conditions. The results showed that under aerobic conditions, both fhp
      and fhpR promoters are induced by ROS generated by the stressors. Thus, the
      Fhp/FhpR system is implicated in the oxidative stress response. ROS-induced fhp
      promoter activity was dependent on FhpR, PA0779, and PA3697 regulators. Tert
      butyl hydroperoxide-induced fhpR promoter activity was found to be highly
      repressed by PA0779, and FhpR showed negative autoregulation of its own promoter.
      Under low-oxygen conditions, the activity of the fhp promoter was not inducible
      by ROS, but fhpR promoter activity was induced by paraquat, and hydrogen peroxide
      was repressed in both cases by the regulators PA0779 and PA3697.

PMID- 19767837
TI  - Clonal relationships determined by multilocus sequence typing among
      enteropathogenic Escherichia coli isolated in Brazil.
AB  - Enteropathogenic Escherichia coli (EPEC) infections are a leading cause of
      infantile diarrhea in developing nations. Multilocus sequence typing (MLST)
      characterizes bacterial strains based on the sequences of internal fragments in
      housekeeping genes. Little is known about strains of EPEC analyzed by MLST from
      Brazil. In this study, a diverse collection of 29 EPEC strains isolated from
      patients with diarrhea, admitted to the University Hospital of Ribeirao Preto,
      was characterized by MLST. Strain analysis demonstrated 22 different sequence
      types (STs), of which almost half (48%) were new, indicating a high genotype
      diversity. The 22 STs were divided by eBURST into 12 clonal complexes. It was not
      possible to correlate typical and atypical EPEC with other strains in the MLST
      database. This is the first study that analyzed EPEC strains from South America
      that are included in the E. coli MLST database. Nine (31%) out of 29 strains are
      part of the CC10 clonal complex, the major clonal complex in the database, which
      comprises 174 strains and 86 different STs, suggesting that these strains might
      be the most important intestinal pathogenic E. coli worldwide. Genetic
      relationships between typical and atypical EPEC, enterohemorrhagic E. coli, and
      enteroaggregative E. coli strains were not established by MLST.

PMID- 19767836
TI  - Identification of oligopeptides mimicking the receptor-binding domain of Hantaan
      virus envelope glycoprotein from a phage-displayed peptide library.
AB  - Attachment of enveloped viruses to cells is triggered by the receptor-binding
      domain (RBD) on envelope glycoproteins (GP) binding to receptors located on the
      cell surface. To date, recognized receptors and RBD of hantaan virus (HTNV) have
      not been exactly defined. In this study, one monoclonal antibody (MAb) 3G1
      possessing high neutralizing activity, which is directed against HTNV envelope
      glycoprotein G2, was used to determine the crucial motif of RBD. Peptide ligands
      binding to MAb 3G1 were selected from a 12 amino acid peptide library displayed
      on filamentous phages. After 3 rounds of selection, the binding capacity between
      phages and MAb 3G1 was examined byELISA. Afterwards the positive phage clones
      with high binding activity to MAb 3G1 were chosen and sequenced. The peptide
      sequences of positive phage clones were compared with that of HTNV 76-118 strain
      G2. A motif Y/F/WPW(X)HX1-2HY, aligned to the primary sequences of G2
      96YPWHTAKCHY105, was identified from the peptide inserts in the 9 positive
      clones. Positive phages and synthesized peptide containing the motif were bound
      significantly to virus-susceptible cell (Vero-E6) membranes by ELISA and
      immunofluorescence assay, respectively. Therefore, the sequence on G2 between
      amino acid 96 and 105 may be a key motif of HTNV RBD recognized by viral
      receptors on target cell membranes. Further characterization of the motif would
      provide useful information in understanding of the cellular entry of HTNV.

PMID- 19767838
TI  - A novel phylogenetic group within Thozetella (Chaetosphaeriaceae): a new taxon
      based on morphology and DNA sequence analyses.
AB  - A new species, Thozetella pinicola, was isolated from leaf litter of Pinus
      elliottii Engelm. in Hong Kong. This taxon is described and compared with
      existing species in the genus. It occurs on the substrate as creamy white
      sporodochia and has short black conidiophores. Morphological characters are
      typical of Thozetella and it most closely resembles Thozetella falcata,
      Thozetella gigantea and Thozetella nivea, but may be distinguished by its
      distinct microawns and different conidial size. To gain further taxonomic insight
      into the phylogenetic relationships of our new taxon and its allies, we sequenced
      and analysed 6 different regions of 3 genes (ribosomal DNA and protein coding
      genes: RNA polymerase II largest subunit (RBP2) and b-tubulin). Resulting
      phylogenies are compared with existing morphological information. Molecular data
      support the relationship between Thozetella species and the Chaetosphaeriaceae
      (Chaetosphaeriales, Sordariomycetes). In addition, we recovered a new
      phylogenetic lineage (or group) within the existing phylogenetic framework of
      Thozetella as previously proposed. In particular, there is a close association
      between T. pinicola and T. nivea, which is strongly supported. The affinities of
      these 2 newly sequenced taxa are discussed in light of morphological and
      molecular characters.

PMID- 19767840
TI  - Disruption of the 2-methylcitric acid cycle and evaluation of poly-3
      hydroxybutyrate-co-3-hydroxyvalerate biosynthesis suggest alternate catabolic
      pathways of propionate in Burkholderia sacchari.
AB  - The objective of the present work was to evaluate the relevance of the 2
      methylcitric acid cycle (2MCC) to the catabolism of propionate in Burkholderia
      sacchari. Two B. sacchari mutants unable to grow on propionate were obtained: one
      disrupted in acnM, and the other in acnM and prpC deleted. An operative 2MCC
      significantly reduces the bacterial ability to incorporate 3-hydroxyvalerate
      (3HV) into a biodegradable copolyester accumulated from carbohydrates plus
      propionate. The efficiency of the mutants in converting propionate to 3HV units
      (Y(3HV/prp)) increased from 0.09 g*g(-1) to 0.81-0.96 g*g(-1), indicating that
      acnM and prpC are both essential for growth on propionate. None of the mutations
      resulted in achievement of the maximum theoretical Y3HV/prp (1.35 g*g(-1)). When
      increasing concentrations of propionate were supplied, decreasing values of
      Y3HV/prp were observed. The results obtained corroborate the hypothesis of the
      presence of other propionate catabolic pathways in B. sacchari. The 2MCC would be
      the more operative pathway, but a second pathway, which remains to be elucidated,
      would assume more importance under propionate concentrations of 1 g*L(-1) or
      higher. The efficiency in converting propionate to 3HV units can be improved by
      decreasing the propionate concentrations, owing to the role of the 2MCC.

PMID- 19767841
TI  - Classical swine fever virus Erns glycoprotein antagonizes induction of interferon
      beta by double-stranded RNA.
AB  - Classical swine fever virus (CSFV) is capable of counteracting innate cellular
      antiviral responses by inhibiting type I interferon (IFN)-alpha/beta induction. A
      function associated with CSFV N(pro), with respect to the inhibition of IFN-beta
      production, has been clearly elucidated. In this study, we explored the role of
      CSFV E(rns) in IFN-beta induction by exogenous double-stranded (ds) RNA.
      Synthetic dsRNA (poly (IC)) was used as an exogenous stimulus to trigger IFN-beta
      induction. CSFV E(rns) inhibited IFN-beta promoter-driven luciferase activity
      induced by poly (IC) in different cell lines, and the inhibitory effect was dose
      dependent. Moreover, E(rns) reduced IFN-beta mRNA synthesis and blocked IFN
      alpha/beta production induced by poly (IC), suggesting that this inhibition
      occurs at the transcriptional level. Furthermore, E(rns) counteracted poly (IC)
      mediated IFN-beta induction independent of its ribonuclease activity. In
      conclusion, CSFV E(rns) antagonizes extracellular dsRNA-mediated IFN-beta
      expression. These findings contribute to our understanding of the pathogenesis of
      CSFV.

PMID- 19767843
TI  - Global responses of Escherichia coli to adverse conditions determined by
      microarrays and FT-IR spectroscopy.
AB  - The global gene expression and biomolecular composition in an Escherichia coli
      model strain exposed to 10 adverse conditions (sodium chloride, ethanol,
      glycerol, hydrochloric and acetic acid, sodium hydroxide, heat (46 degrees C),
      and cold (15 degrees C), as well as ethidium bromide and the disinfectant
      benzalkonium chloride) were determined using DNA microarrays and Fourier
      transform infrared (FT-IR) spectroscopy. In total, approximately 40% of all
      investigated genes (1682/4279 genes) significantly changed expression, compared
      with a nonstressed control. There were, however, only 3 genes (ygaW (unknown
      function), rmf (encoding a ribosomal modification factor), and ghrA (encoding a
      glyoxylate/hydroxypyruvate reductase)) that significantly changed expression
      under all conditions (not including benzalkonium chloride). The FT-IR analysis
      showed an increase in unsaturated fatty acids during ethanol and cold exposure,
      and a decrease during acid and heat exposure. Cold conditions induced changes in
      the carbohydrate composition of the cell, possibly related to the upregulation of
      outer membrane genes (glgAP and rcsA). Although some covariance was observed
      between the 2 data sets, principle component analysis and regression analyses
      revealed that the gene expression and the biomolecular responses are not well
      correlated in stressed populations of E. coli, underlining the importance of
      multiple strategies to begin to understand the effect on the whole cell.

PMID- 19767842
TI  - The IL-6-deficient mouse exhibits impaired lymphocytic responses to a vaccine
      combining live Leishmania major and CpG oligodeoxynucleotides.
AB  - We have previously reported that vaccination with CpG oligodeoxynucleotides
      delivered concomitantly with live Leishmania major (Lm/CpG) eliminates lesions
      associated with live vaccination in C57BL/6 mice. The absence of lesions is at
      least in part a result of the CpG DNA-mediated activation of dermal dendritic
      cells to produce cytokines such as interleukin (IL)-6. Wild-type C57BL/6 mice and
      IL-6-/- mice were immunized with the Lm/CpG vaccine and monitored for the
      development of lesions. IL-6-/- mice developed extensive, nonhealing lesions
      following live vaccination. The analysis of the inoculation site and draining
      lymph nodes of the IL-6-/- mice revealed a constitutive reduction in lymphocyte
      numbers, particularly CD4+ T cells. Live vaccination resulted in the specific
      expansion of CD4+Foxp3+ regulatory T cells in the knockout mice, and in a
      decrease of CD4+ IFN-gamma -producing cells. These results indicate that IL-6-/-
      mice may have collateral immune defects that could influence the development of
      the natural immune response to pathogens, vaccines, or other inflammatory
      stimuli.

PMID- 19767844
TI  - Production and biochemical characterization of a type B ferulic acid esterase
      from Streptomyces ambofaciens.
AB  - For the first time, the presence of a ferulic acid esterase (FAE) was
      demonstrated in Streptomyces ambofaciens. This extracellular enzyme was produced
      on a range of lignocellulosic substrates. The maximal level of activity was
      detected in the presence of either destarched wheat bran or oat spelt xylan as
      the sole carbon source. We found that 1% (m/v) of destarched wheat bran was the
      optimal concentration to induce its production. With this inducer, no ferulic
      acid dimers were released from the cell wall by the produced FAE. Interestingly,
      rape cattle cake (Brassica napus), which does not contain esterified ferulic
      acid, was also shown to induce the production of the FAE from S. ambofaciens. The
      FAE was partially purified from the culture supernatant. The purified enzyme was
      optimally active at pH 7 and 40 degrees C. The substrate specificity of the FAE
      from S. ambofaciens was investigated: the highest activity was determined with
      methyl p-coumarate, methyl ferulate, and methyl cinnamate. Furthermore, the FAE
      required a certain distance between the benzene ring and the ester bond to be
      active. According to these biochemical characteristics, the FAE from S.
      ambofaciens has been classified as a type B FAE.

PMID- 19767845
TI  - Molecular characterization of the pL40 protein in Leptospira interrogans.
AB  - Leptospirosis is a widespread zoonotic disease caused by pathogenic leptospires.
      The identification of outer membrane proteins (OMPs) conserved among pathogenic
      leptospires, which are exposed on the leptospiral surface and expressed during
      mammalian infection, has become a major focus of leptospirosis research. pL40, a
      40 kDa protein coded by the LA3744 gene in Leptospira interrogans, was found to
      be unique to Leptospira. Triton X-114 fractionation and flow cytometry analyses
      indicate that pL40 is a component of the leptospiral outer membrane. The
      conservation of pL40 among Leptospira strains prevalent in China was confirmed by
      both Western blotting and PCR screening. Furthermore, the pL40 antigen could be
      recognized by sera from guinea pigs and mice infected with low-passage L.
      interrogans. These findings indicate that pL40 may serve as a useful
      serodiagnostic antigen and vaccine candidate for L. interrogans.

PMID- 19767846
TI  - Characterization of tetracycline- and ampicillin-resistant Escherichia coli
      isolated from the feces of feedlot cattle over the feeding period.
AB  - The objective of this study was to investigate tetracycline and ampicillin
      resistance in Escherichia coli isolated from the feces of 50 crossbred steers
      housed in 5 feedlot pens. The steers were not administered antibiotics over a 246
      day feeding period. A total of 216 isolates were selected for further
      characterization. The E. coli isolates were selected on MacConkey agar or on
      MacConkey agar amended with ampicillin (50 microg/mL) or tetracycline (4
      microg/mL). Pulsed-field gel electrophoresis (PFGE) typing (XbaI digestion),
      screening against 11 antibiotics, and multiplex PCR for 14 tet and 3 beta
      lactamase genes were conducted. Prevalence of antimicrobial resistance in E. coli
      at each sampling day was related both temporally and by pen. Multiplex PCR
      revealed that tet(B) was most prevalent among tetracycline-resistant isolates,
      whereas beta-lactamase tem1-like was detected mainly in ampicillin-resistant
      isolates. Our results suggest that antimicrobial resistance in E. coli
      populations persists over the duration of the feeding period, even in the absence
      of in-feed antibiotics. Many of the isolates with the same antibiograms had
      indistinguishable PFGE patterns. Characterization of the factors that influence
      the nature of this nonselective resistance could provide important information
      for consideration in the regulation of in-feed antimicrobials for feedlot cattle.

PMID- 19767847
TI  - Influence of DNA conformation and role of comA and recA on natural transformation
      in Ralstonia solanacearum.
AB  - Naturally competent bacteria such as the plant pathogen Ralstonia solanacearum
      are characterized by their ability to take up free DNA from their surroundings.
      In this study, we investigated the efficiency of various DNA types including
      chromosomal linear DNA and circular or linearized integrative and (or)
      replicative plasmids to naturally transform R. solanacearum. To study the
      respective regulatory role of DNA transport and maintenance in the definite
      acquisition of new DNA by bacteria, the natural transformation frequencies were
      compared with those obtained when the bacterial strain was transformed by
      electroporation. An additional round of electrotransformation and natural
      transformation was carried out with the same set of donor DNAs and with R.
      solanacearum disrupted mutants that were potentially affected in competence (comA
      gene) and recombination (recA gene) functions. Our results confirmed the critical
      role of the comA gene for natural transformation and that of recA for
      recombination and, more surprisingly, for the maintenance of an autonomous
      plasmid in the host cell. Finally, our results showed that homologous
      recombination of chromosomal linear DNA fragments taken up by natural
      transformation was the most efficient way for R. solanacearum to acquire new DNA,
      in agreement with previous data showing competence development and natural
      transformation between R. solanacearum cells in plant tissues.

PMID- 19767848
TI  - Detection of a novel bacterium associated with spores of the arbuscular
      mycorrhizal fungus Gigaspora margarita.
AB  - With PCR-denaturing gradient gel electrophoresis analysis, two bacterial 16S rRNA
      gene V3 region sequences, 7A and 7B, were detected in association with the
      crushed spores of the arbuscular mycorrhizal fungus Gigaspora margarita W.N.
      Becker & I.R. Hall 1976 MAFF520054. DNA sequencing and phylogenetic analysis
      revealed that 7B was mostly related to the documented cytoplasm endosymbiotic
      bacterium Candidatus Glomeribacter gigasporarum of G. margarita, but 7A could not
      be confidently assigned to a known taxon. Further characterization of 7A was
      conducted by obtaining its almost complete 16S rRNA gene sequence via PCR
      amplification and sequencing. BLAST search indicates that the 16S rRNA gene
      sequence did not match any identified species sequences in the GenBank database.
      Further detection revealed that 7A was also associated with the clean G.
      margarita MAFF520054 spores that were obtained by the surface-sterilized method
      or dual culture with Ri T-DNA transformed carrot roots. Many ellipse-shaped or
      egg-shaped bacterium-like organisms were clustered in layer 3 of the fungal spore
      wall by transmission electron microscopy observation. Our results indicate that
      7A represents a novel bacterial population associated with G. margarita
      MAFF520054 spores, and its doubtless location (wall or cytoplasm) remains unclear
      based on the present data.

PMID- 19767849
TI  - DNA extraction procedure affects organic-aggregate-attached bacterial community
      profiles from a shallow eutrophic lake.
AB  - Organic aggregates (OA) in aquatic ecosystems harbour diverse microbial
      communities. The colonization and growth of OA-attached bacteria are important
      processes in the degradation and transformation of the particles. The development
      of efficient and comparative DNA extraction methods is one of the most critical
      steps in the study of the composition and diversity of OA-attached bacterial
      communities. To evaluate whether different DNA extraction procedures affect the
      measurement of bacterial community composition, we compared four in situ lysis
      procedures using OA from three locations in a shallow eutrophic lake (Lake Taihu,
      China). The extracted DNA was analyzed using denaturing gradient gel
      electrophoresis profiles. We found that the choice of DNA extraction protocol had
      a significant influence on the fingerprints of the OA-attached bacterial
      community. This was shown not only in the number of bands but also in their
      relative representation of certain DNA bands. Using the bead-beating DNA
      extraction method in the presence of hexadecyltrimethylammonium bromide, we found
      that crude microbial DNA could be extracted efficiently from different OA types.
      This protocol is reproducible and gives very pure DNA of relatively high
      molecular mass. More importantly, the protocol provided more representative and
      informative data on the diversity of OA-attached bacterial communities.

PMID- 19767850
TI  - Altitudinal distribution of microfungi associated with Betula ermanii leaf litter
      on Mt. Rishiri, northern Japan.
AB  - The altitudinal distribution of microfungi associated with Betula ermanii Cham.
      leaf litter was investigated on Mt. Rishiri (1719 m), northern Japan. Fallen
      leaves were collected at five sites of different altitudes (approximately 300,
      600, 900, 1200, and 1500 m above sea level) along a transect on the northern
      slope of Mt. Rishiri. A total of 35 species were isolated from Betula leaf litter
      of which 12 occurred frequently and were regarded as dominant microfungi. Species
      richness, diversity, and equitability of microfungal assemblages were lower at
      Site 1500 than at the other sites. Similarities in species composition were
      relatively high among Sites 300, 600, and 900, but similarities between these
      sites and sites at the higher altitudes (i.e., Sites 1200 and 1500) were
      relatively low. Similarity of species composition was relatively low between
      Sites 1200 and 1500. Cluster analysis showed that the 12 major microfungal
      species were classified into four groups according to their pattern of
      altitudinal distribution that peaked at Sites 600, 900, 1200, and 1500,
      respectively. These results suggest that the diversity and species composition of
      Betula microfungi are sensitive to environmental changes along the altitudinal
      transect on Mt. Rishiri, and this is especially so at the altitudes higher than
      approximately 1200 m. This implies that future environmental changes will have
      impacts on mountainous ecosystems through the changes in diversity and functional
      aspects of microfungal assemblages.

PMID- 19767851
TI  - Polyhydroxyalkanoates production by actinobacteria isolated from soil.
AB  - Polyhydroxyalkanoates (PHAs) are biodegradable and renewable polymers produced by
      a wide range of bacterial groups. New microbial bioprospection approaches have
      become an important way to find new PHA producers and new synthesized polymers.
      Over the past years, bacteria belonging to actinomycetes group have become known
      as PHA producers, such as Nocardia and Rhodococcus species, Kineosphaera limosa
      Liu et al. 2002, and, more recently, Streptomyces species. In this paper, we
      disclose that there are more actinobacteria PHA producers in addition to the
      genera cited. Some unusual genera, such as Streptoalloteichus, and some genera
      frequently present in soil, such as Streptacidiphilus, have been found. Thirty
      four isolates were able to accumulate poly(3-hydroxybutyrate) and a number of
      these have traces of poly(3-hydroxyvalerate) when cultivated on glucose or
      glucose and casein as carbon source. Furthermore, some strains showed traces of
      medium chain length PHA. Transmission electron microscopy demonstrated that the
      PHA accumulation occurs in hyphae and spores.

PMID- 19767852
TI  - Differential response of Pichia guilliermondii spoilage isolates to biological
      and physico-chemical factors prevailing in Patagonian wine fermentations.
AB  - Pichia guilliermondii can produce volatile phenols in the initial stages of wine
      fermentation; however, its response to different wine stress conditions has been
      poorly studied. In this work, we present an analysis of the response of 23 P.
      guilliermondii indigenous isolates to physical and chemical wine stress factors
      and to indigenous wine killer yeasts. Principal coordinates analysis (PCoA),
      based on data obtained from response patterns, was carried out to evaluate the
      relationships among the isolates. Major differences among the isolates were
      detected in media plates containing 8% ethanol and in those containing 280 g/L
      glucose. PCoA identified 3 clusters of isolates with different stress response
      patterns, indicating a relationship between the tolerance to these compounds and
      the origin of the isolates. Pichia guilliermondii isolates were sensitive to the
      toxins produced by the species Hanseniaspora uvarum, Metschnikowia pulcherrima,
      Wickerhamomyces anomala (ex Pichia anomala), and Pichia kluyveri, with a maximum
      level of sensitivity against W. anomala (91% on average). Those isolates obtained
      from fermenting must proved to be more resistant to killer yeasts than those
      obtained from grape surfaces. The combined evaluation of the response to physico
      chemical and biological factors presented in this work could be a useful standard
      protocol for the evaluation of the potential spoilage capacity of yeasts in
      winemaking.

PMID- 19767853
TI  - Amplified ribosomal DNA restriction analysis of free-living bacteria present in
      the headbox of a Canadian paper machine.
AB  - The headbox water is the main source of bacterial contamination of paper
      machines. Identification of these bacterial contaminants could be an asset in
      developing specific control methods. An amplified ribosomal DNA restriction
      analysis (ARDRA) was carried out to characterize the bacterial communities
      associated with the headbox water of a paper machine in a Canadian mill in
      February and July 2006. Eight bacterial genera were identified as the main
      colonizers present in the headbox water. The genus Meiothermus appeared to be the
      dominant bacterial group in the Canadian paper machine. Some variation was
      observed between the February and July clone libraries. Bacterial genera such as
      Chelatococcus and Hydrogenophilus were only detected in February or in July,
      respectively. Furthermore, the proportion of Tepidimonas clones in the libraries
      was higher in July than in February. The metabolic profile of the February and
      July communities, determined using Biolog EcoPlates, also suggested that temporal
      variation occurred within the bacterial populations that colonized the headbox of
      the paper machine.

PMID- 19767854
TI  - Sulfate-reducing bacteria in leachate-polluted aquifers along the shore of the
      East China Sea.
AB  - The diversity of sulfate-reducing bacteria (SRB) in the aquifer underlying the
      Laogang Landfill along the shore of the East China Sea was investigated. The DNA
      extracted from 15 groundwater samples was subjected to PCR amplification of the
      dissimilatory sulfite reductase (dsr) gene. Full-length dsrAB amplicons
      (approximately 1.9 kb) were then used to construct 4 clone libraries, while the
      dsrB amplicons (approximately 350 bp) were used for denaturing gradient gel
      electrophoresis (DGGE) analysis. The clones in the 4 libraries covered all
      cultured SRB lineages, as well as a deeply branching clade not affiliated with
      any cultured SRB. In addition, nearly 80% of the 388 clones in the 4 libraries
      were similar to sequences of the Deltaproteobacteria, Desulfobacteriaceae,
      Desulfovibrionales, Syntrophaceae, and Desulfobulbaceae. Furthermore, a wide
      variety of marine SRB was detected, which indicated that seawater has infiltrated
      the aquifer. Indeed, the DGGE profiles revealed obvious variations in SRB
      diversity among the 15 samples, which clustered in accordance with the sulfate
      concentration of the samples ([SO4(2-)]). Moreover, the sulfate concentrations
      and SRB diversity along the leachate plume did not show regular variation, which
      suggests the impact of both groundwater flow and seawater intrusion.

PMID- 19767855
TI  - Leaf-associated bacteria from transgenic white poplar producing resveratrol-like
      compounds: isolation, molecular characterization, and evaluation of oxidative
      stress tolerance.
AB  - The aim of this study was the isolation and characterization of the culturable
      bacteria inhabiting the leaves of transgenic white poplars (Populus alba L.
      'Villafranca') engineered with the StSy gene for the production of resveratrol
      like compounds. Resveratrol glucosides are available in small amounts from
      natural sources or by expensive chemical synthesis procedures. An alternative
      approach for the large-scale production of these relevant pharmaceuticals is the
      use of transgenic plants as bioreactors, although the occurrence of novel
      molecules in plants growing under field conditions might interfere, to some
      extent, with the associated microbial population. Both epiphytes and endophytes
      were isolated from the leaves of 2 StSy transgenic lines producing resveratrol
      glucosides and from an untransformed plant line grown in a greenhouse. Eleven
      isolates were recovered and classified as members of the genus Bacillus by 16S
      rDNA-based analysis. In addition, 2 isolates were classified as members of the
      Curtobacterium and Kocuria genera, respectively. Tolerance to hydrogen peroxide,
      UV-C, and paraquat was evaluated, as were the swimming and swarming motility of
      the leaf-associated bacteria. Interestingly, the isolates recovered from
      transgenic tissues showed the ability to withstand oxidative stress compared with
      isolates recovered from the untransformed poplar line. In vitro bioassays showed
      that trans-resveratrol inhibited both the swarming and swimming motilities in all
      the tested bacteria. The effects of trans-resveratrol on flagellin production,
      required for motility, were also investigated by immunoblot analysis.

PMID- 19767856
TI  - Involvement of RecG in H2O2-induced damage repair in Deinococcus radiodurans.
AB  - Deinococcus radiodurans (ex Raj et al. 1960) Brooks and Murray 1981 is well known
      for its efficient repair of various types of physically or chemically induced DNA
      damage caused by ionizing and ultraviolet radiation or H2O2. RecG codes for a
      helicase that is known to be involved in repairing oxidative damage in other
      bacterium. In this work, we constructed a DRrecG deletion mutant and investigated
      its possible role in H2O2-induced damage. The results showed that the deletion of
      DRrecG resulted in an obvious growth defect and great decrease of radioresistance
      of D. radiodurans to gamma radiation and H2O2. We also defined the
      transcriptional profiles of the recG mutant and wild-type strain with and without
      treatment with H2O2. These results suggested that DRrecG is important for DNA
      repair during oxidative damage.

PMID- 19767857
TI  - Enhanced enrichment and detection of thermotolerant Campylobacter species from
      water using the Portable Microbe Enrichment Unit and real-time PCR.
AB  - An enhanced enrichment using the Portable Microbe Enrichment Unit (PMEU) with the
      microaerobic bubbling of broths was applied for the detection of thermotolerant
      Campylobacter species from water. This PMEU enrichment was compared with the
      conventional static enrichment of the international standard ISO 17995:2005. In
      addition, Campylobacter detection after enrichment using a real-time PCR
      detection was compared with colony counts. The tests with stressed Campylobacter
      jejuni cells in drinking water indicated that the PMEU enrichment yielded a
      significantly higher number of Campylobacter cells in the Bolton broth compared
      with the conventional static incubation. Application of the real-time PCR
      technique shortened the Campylobacter detection time. This combination of method
      modifications can be used for Campylobacter detection from water and adds
      methodological repertoire for the rapid survey and management of waterborne
      outbreaks.

PMID- 19767858
TI  - In vitro maturation and migration of immature dendritic cells after chemokine
      receptor 7 transfection.
AB  - Dendritic cells are specialized antigen-presenting cells that regulate immunity
      and tolerance. Chemokine receptor 7 (CCR7), which is expressed by mature
      dendritic cells, mediates the migration of the cells to secondary lymphoid organs
      and thus regulates immune responses. It has been demonstrated that immature
      dendritic cells can induce immune tolerance, but they do not express CCR7 and
      cannot migrate to secondary lymphoid organs. We transfected immature dendritic
      cells with a recombinant adenovirus carrying the CCR7 gene to obtain immature
      dendritic cells with the ability to migrate. The maturity of the cells was
      monitored by scanning electron microscopy and flow cytometry. In addition, we
      assessed the ability of cells to migrate and the function of the cells using in
      vitro chemotactic and mixed leukocyte reaction assays. The results showed that
      immature dendritic cells became semi-mature, exhibiting a mild upregulation of co
      stimulatory molecular expression and a few dendritic processes.
      Immunofluorescence assay and Western blotting indicated that CCR7 protein
      expression increased significantly in immature dendritic cells following CCR7
      gene transfection. The in vitro chemotactic assay showed a significantly enhanced
      ability to migrate in response to CCL19 following CCR7 gene transfection.
      Moreover, transfected cells showed an enhanced ability to stimulate allogeneic T
      cell proliferation in vitro, but their ability was significantly weaker than that
      of mature dendritic cells. Interleukin-10 inhibited the differentiation and
      maturation of immature dendritic cells. It is concluded that, following CCR7 gene
      transfection, immature dendritic cells exhibit an enhanced ability to migrate and
      some of the characteristics of mature cells. Thus, these cells are of potential
      clinical significance in studies of immune tolerance induction during skin
      grafting after severe burns.

PMID- 19767859
TI  - Truncated hemoglobins in Frankia CcI3: effects of nitrogen source, oxygen
      concentration, and nitric oxide.
AB  - Frankia strain CcI3 produces 2 truncated hemoglobins, HbN and HbO. Using ion
      exchange chromatography, we characterized the expression of the relative amounts
      of HbN and HbO in -N (nitrogen-fixing) cultures and +N (nitrogen-supplemented)
      cultures. The -N cultures maintained an approximately constant ratio of HbO to
      HbN throughout the life of the culture, with HbO constituting 80%-85% of the
      total hemoglobin produced. In contrast, in +N cultures, HbN was observed to
      increase over time and HbO decreased. Total hemoglobin as a fraction of total
      protein was approximately constant throughout the growth phase in -N cultures,
      while it decreased somewhat in +N cultures. Subjecting -N cultures to a NO
      generator resulted in increased production of HbN, relative to the controls.
      Nitrite accumulated in +N cultures, but not in -N cultures. This suggests that
      the greater amount of HbN in +N cultures might be due to NO produced by the
      reduction of nitrite. The effects of O2 concentration were determined in +N
      cultures. Cultures grown in 1% O2 produced about 4 times more HbO than cultures
      grown in 20% O2. Overall, these results provide evidence for a role of HbN in NO
      oxidation and for a role of HbO in adaptation to low oxygen concentrations.

PMID- 19767860
TI  - Isolation of a spermatozoal immobilization factor from Staphylococcus aureus
      filtrates.
AB  - Staphylococcus aureus isolated from the cervix of an infertile woman was found to
      cause complete immobilization of human spermatozoa in vitro. Only the cell
      culture and cell-free supernatant showed immobilization activity, indicating that
      the sperm immobilization factor might be released extracellularly by the organism
      because no activity was observed with the washed cells. Heat treatment of the
      supernatant at 60 degrees C for 10 min waived its immobilizing activity,
      indicating that the active component may be a protein. The bioactive molecule
      from the supernatant was purified to homogeneity by ammonium sulfate
      precipitation, gel permeation chromatography, and ion exchange chromatography.
      Sperm immobilization factor (SIF) was found to be an approximately 20 kDa
      protein. SIF at a concentration of 10 microg/mL was required to cause 100%
      immobilization of human spermatozoa after 30 min of incubation at 37 degrees C,
      whereas a concentration of 150 microg/mL caused immediate immobilization, and a
      concentration of 200 microg/mL resulted in instant loss of viability of human
      spermatozoa, observed by eosin-nigrosin staining. Scanning electron microscopy
      showed that the treatment of human spermatozoa with SIF caused multiple defects
      in the head, midpiece, neck, and tail region of human spermatozoa.

PMID- 19767861
TI  - Influence of arbuscular mycorrhizae on the root system of maize plants under salt
      stress.
AB  - Salt stress has become a severe global problem, and salinity is one of the most
      important abiotic factors limiting plant growth and yield. It is known that
      arbuscular mycorrhizal (AM) fungi decrease plant yield losses under salinity.
      With the aim of determining whether AM inoculation would give an advantage to
      root development under salt stress, a greenhouse experiment was carried out with
      AM or without AM fungi. Maize plants were grown in a sand and soil mixture with 5
      NaCl levels (0, 0.5, 1.0, 1.5, and 2.0 g/kg dry substrate) for 55 days, following
      15 days of nonsaline pretreatment. At all salt levels, mycorrhizal plants had
      higher dry shoot and root mass, higher root activity, and lower root to shoot
      ratios than non-mycorrhizal plants. In salt-free soil, root length, root surface
      area, root volume, and number of root tips and forks were significantly larger in
      mycorrhizal plants than in non-mycorrhizal plants, whereas, under salt stress,
      average root diameter and root volume of mycorrhizal plants were larger than
      those of non-mycorrhizal plants. Regardless of the NaCl level, mycorrhizal plants
      had lower specific root length, lower percentage of root length in the 0-0.2 mm
      diameter class, and higher percentage of root length in both the 0.2-0.4 mm and
      0.4-0.6 mm diameter classes, which suggests that the root system shows a
      significant shift towards a thicker root system when maize plants were inoculated
      with Glomus mosseae (Nicolson & Gerdemann). The results presented here indicate
      that the improvements in root activity and the coarse root system of mycorrhizal
      maize may help in alleviating salt stress on the plant.

PMID- 19767862
TI  - Oxidative stress response of Mycosphaerella fijiensis, the causal agent of black
      leaf streak disease in banana plants, to hydrogen peroxide and paraquat.
AB  - Mycosphaerella fijiensis causes black leaf streak disease in banana and plantain.
      This fungus is usually attacked by reactive oxygen species secreted by the plant
      or during exposure to fungicide, however, little is known about the antioxidant
      response of the fungus. In this study, mycelia were observed to totally decompose
      30 mmol/L of hydrogen peroxide (H2O2) within 120 min, liberating oxygen bubbles,
      and also to survive in concentrations as high as 100 mmol/L H2O2. The oxidative
      stress responses to H2O2, paraquat, and hydroquinone were characterized in terms
      of the activities of catalase and superoxide dismutase (SOD). Two active catalase
      bands were seen in native PAGE induced by H2O2. Band I had monofunctional
      activity and band II had bifunctional catalase-peroxidase activity. Two isozymes
      of SOD, distinguishable by their cyanide sensitivity, were found; CuZnSOD was the
      main one. The combination of H2O2 and 3-aminotriazole reduced the accumulation of
      biomass up to 40% compared with exposure to H2O2 alone, suggesting that catalase
      is important for the rapid decomposition of H2O2 and has a direct bearing on cell
      viability. The results also suggest that the superoxide anion formed through the
      redox of paraquat and hydroquinone has a greater effect than H2O2 on the cellular
      viability of M. fijiensis.

PMID- 19767863
TI  - Prospective study applying spoligotyping directly to DNA from sputum samples of
      patients suspected of having tuberculosis.
AB  - A prospective study was designed to evaluate the clinical usefulness of
      spoligotyping applied directly to sputum samples. Patients suspected of having
      tuberculosis were recruited at the Hospital Sanatorio Partenon in Porto Alegre,
      Brazil. Of the 197 samples included in the analysis, 175 (88.8%) yielded a
      spoligotyping result that fully matched that obtained from culture. Low bacillary
      samples presented lower accuracy (50%). From 135 Mycobacterium tuberculosis
      spoligopatterns, we identified 44 different spoligotypes, of which 21 were shared
      patterns and 23 were unique. T1 was the most frequent subfamily. The genotyping
      strategy proposed here presents a short turnaround time and could be helpful in
      providing rapid information on strain identities in a clinical setting.

PMID- 19767864
TI  - The fate and efficacy of benomyl applied to field soils to suppress activity of
      arbuscular mycorrhizal fungi.
AB  - A systematic application of the fungicide benomyl was used to follow up the
      suppression of arbuscular mycorrhizal (AM) colonization and to determine its
      fungitoxic activity and persistence at different depths. Repeated applications of
      benomyl reduced AM colonization mainly in the upper 0-4 cm layer of the treated
      soils. Furthermore, AM colonization decreased with soil depth. The activity and
      persistence of this fungicide was reduced over small changes in depth in the
      first 10 cm of the soil profile beneath a semiarid herbland at Brookfield
      Conservation Park (South Australia). Repeated applications of the fungicide only
      slightly increased the levels of toxicity in the soils, probably because of
      biodegradation of the fungicide in soils with a recent history of exposure to the
      fungicide. The decline in fungicide activity at depth was correlated with a
      decline in the suppressive effect of the fungicide on the activity of AM fungi.

PMID- 19767865
TI  - Abundance of culturable versus viable Escherichia coli in freshwater.
AB  - Approved methods traditionally used for Escherichia coli enumeration in waters
      are culture-based. However, these methods can underestimate the E. coli abundance
      in aquatic systems because they do not take into account cells that remain viable
      but have lost the ability to grow in or on culture media. We investigated, in
      freshwater samples, the abundance of (i) culturable E. coli, enumerated by the
      most probable number microplate method and (ii) viable E. coli, estimated using a
      procedure called DVC-FISH, which couples fluorescent in situ hybridization (FISH)
      and a viability testing technique (direct viable count (DVC)). The ratio of
      culturable to viable E. coli was close to 1 in highly contaminated waters
      (samples with a high concentration of culturable E. coli), but decreased
      drastically for weakly contaminated samples. This indicates a large fraction of
      viable but nonculturable (VBNC) E. coli in the latter samples. Microcosm
      experiments showed that some environmental factors, such as nutrient scarcity and
      solar irradiation, could lead to the presence of a high proportion of VBNC E.
      coli.

PMID- 19767866
TI  - Comparison of media used to evaluate Rhizobium leguminosarum bivar viciae for
      phosphate-solubilizing ability.
AB  - Rhizobium leguminosarum is well known for its ability to fix nitrogen (N). In
      addition, its capacity to solubilize phosphate (Ph) has been receiving attention
      in recent years. Our ultimate objective was to select a R. leguminosarum bv.
      viciae isolate with superior Ph-solubilizing ability. The first step was to
      identify a culture medium that is sensitive and effective in identifying the
      ability of R. leguminosarum bv. viciae isolates to solubilize Ph. Thirty isolates
      were evaluated for Ph solubilization in broth and on solid formulations of three
      media: yeast mannitol extract (YEM), National Botanical Research Institute
      phosphate nutrient medium (MNBRI), and Pikovskaya phosphate medium (PVK). All
      media contained 5 g/L CaHPO4 as the only phosphorus (P) source. All 30 isolates
      increased the Ph concentration in liquid cultures, but the amount of Ph released
      into solution by individual isolates varied from one medium to another. In
      contrast, only a subset of the 30 isolates solubilized Ph on the solid cultures.
      Furthermore, some of the isolates that were able to solubilize Ph were only able
      to do so on a single medium. Regression analysis revealed no relationship between
      the Ph concentration in the liquid media and the zones of clearing on the solid
      media (p > 0.05). Although the pH of all of the liquid media dropped after 12
      days of growth of the isolates, a relationship between Ph concentration and pH
      existed only for the MNBRI medium (r2 = 0.485, p < 0.001). Increasing the amount
      of N in the MNBRI medium from 0.1 g/L of (NH4)2SO4 to 0.5 g/L of (NH4)2SO4 did
      not affect the amount of Ph in solution, but it profoundly reduced the survival
      of the R. leguminosarum by approximately 50-fold. Consequently, the surviving
      bacteria were either more efficient at solubilizing Ph in the high N media or
      organic acids released from the lysis of the dead cells solubilized the CaHPO4
      source.

PMID- 19767873
TI  - Role of the excessive amounts of circulating catecholamines and glucocorticoids
      in stress-induced heart disease.
AB  - Various stressful stimuli are known to activate the sympathetic nervous system to
      release catecholamines and the hypothalamic-pituitary-adrenal axis to release
      glucocorticoids in the circulation. Although initial actions of both
      catecholamines and glucocorticoids are beneficial for the function of the
      cardiovascular system, their delayed effects on the heart are deleterious.
      Glucocorticoids not only increase plasma levels of catecholamines by inhibiting
      their extraneuronal uptake, but they have also been shown to induce
      supersensitivity to catecholamines in the heart by upregulating different
      components of the betta-adrenoceptor signal transduction system. Low
      concentrations of catecholamines stimulate the heart by promoting Ca2+ movements,
      whereas excessive amounts of catecholamines produce cardiac dysfunction by
      inducing intracellular Ca2+ overload in cardiomyocytes. Several studies have
      shown, however, that under stressful conditions high concentrations of
      catecholamines become oxidized to form aminolutins and generate oxyradicals.
      These oxidation products of catecholamines have been demonstrated to produce
      coronary spasm, arrhythmias, and cardiac dysfunction by inducing Ca2+-handling
      abnormalities in both sarcolemmal and sarcoplasmic reticulum, defects in energy
      production by mitochondria, and myocardial cell damage. In this article we have
      focused the discussion to highlight the interrelationship between catecholamines
      and glucocorticoids and to emphasize the role of oxidation products of
      catecholamines in the development of stress-induced heart disease.

PMID- 19767874
TI  - Effects of enalapril and sodium depletion on the renin-angiotensin system in
      hydronephrotic mice.
AB  - The effects of enalapril and sodium depletion on renin synthesis and secretion
      were studied in mice with a left hydronephrotic kidney caused by unilateral
      ureteral ligation (UUL). In the control animals, there was no difference in
      plasma renin concentration between the right and left renal veins. In mice with
      left ureteral ligation, the renin concentration in the vein draining the
      hydronephrotic kidney was similar to or lower than that in the aorta under
      control conditions and after either stimulation with enalapril or depletion of
      sodium. Enalapril and sodium restriction increased plasma renin concentration,
      and this increase was due to secretion from the nonhydronephrotic kidney. The
      renin concentration per gram of kidney tissue and the mRNA for renin per gram of
      kidney tissue were similar in both the control and hydronephrotic kidney, and the
      values rose 3-4-fold in both kidneys after enalapril or sodium depletion.
      Immunostaining for renin confirmed these findings and indicated that renin per
      glomerulus was higher in the hydronephrotic kidney. Thus, removal or reduction of
      angiotensin II activity or depletion of sodium stimulated synthetic activity to a
      similar extent in the normal and hydronephrotic kidneys; however, secretion from
      the kidney without a macula densa (hydronephrotic) was not increased. Thus, the
      signals that control synthesis and secretion are different, and for these
      stimuli, secretion appears to require an intact macula densa.

PMID- 19767875
TI  - Impaired renal calcium absorption in mice lacking calcium channel beta 3
      subunits.
AB  - Transgenic mice lacking calcium channel beta3 subunits (CaVbeta3) were used to
      determine the involvement of a multimeric calcium channel in mediating stimulated
      renal calcium absorption. We measured the ability of calcium channel beta3
      subunit-null (CaVbeta3-/-) and wild-type (CaVbeta3+/+) mice to increase renal
      calcium absorption in response to the calcium-sparing diuretic chlorothiazide
      (CTZ). Control rates of fractional sodium excretion were comparable in CaVbeta3-/
      and CaVbeta3+/+ mice and CTZ increased sodium excretion similarly in both
      groups. CTZ enhanced calcium absorption only in wild-type CaVbeta3+/+ mice. This
      effect was specific for diuretics acting on distal tubules because both CaVbeta3
      /- and CaVbeta3+/+ mice responded comparably to furosemide. The absence of beta3
      subunits resulted in compensatory increases of TrpV5 calcium channels, the plasma
      membrane Ca-ATPase, NCX1 Na/Ca exchanger protein, and calbindin-D9k but not
      calbindin-D28k. We conclude that TrpV5 mediates basal renal calcium absorption
      and that a multimeric calcium channel that includes CaVbeta3 mediates stimulated
      calcium transport.

PMID- 19767876
TI  - Hydrogen sulfide attenuates the pathogenesis of pulmonary fibrosis induced by
      bleomycin in rats.
AB  - The present study investigated the role of the endogenous cystathionine gamma
      lyase (CSE) / hydrogen sulfide pathway in the pathogenesis of pulmonary fibrosis.
      Rats treated with intratracheal bleomycin were exposed either to the H2S donor
      NaHS or to saline. The results on day 7 showed that plasma H2S concentration and
      pulmonary CSE activity (H2S production rate) were significantly lower in rats
      treated with bleomycin and saline (fibrosis-alone) than in controls, whereas on
      day 28 plasma H2S concentration was higher and pulmonary CSE activity was the
      same as that of controls. The relative CSE mRNA level in the lungs of rats
      treated with bleomycin was significantly higher than control values on days 7 and
      28. After exposure to NaHS, the total lung hydroxyproline content and the
      malondialdehyde (MDA) content were both significantly lower, with no difference
      observed between NaHS high-dose and low-dose treatments. Further, MDA formation
      stimulated by the free radical-generating system (FRGS) in vitro was lower in
      lung tissue incubated with NaHS than it was in tissue incubated with FRGS alone.
      These results suggest that NaHS administration ameliorated the pulmonary fibrosis
      induced by bleomycin in rats and that this protective effect of H2S may be
      mediated by its antioxidative action.

PMID- 19767877
TI  - Sex and hormonal influences on the nicotine-induced attenuation of isoprenaline
      vasodilations in the perfused rat kidney.
AB  - We previously reported that nicotine impairs betta-adrenoceptor-mediated
      renovascular control in male rats. Here, we investigated the roles of sex and
      estrogen in nicotine-betta-adrenoceptor renal interaction. The effect of nicotine
      on renal vasodilations caused by isoprenaline was evaluated in phenylephrine
      preconstricted perfused kidneys of male and proestrus female rats in absence and
      presence of NG-nitro-<span class="smallcap">l</span>-arginine (<span
      class="smallcap">l</span>-NNA, a NOS inhibitor). The interaction was also studied
      in diestrus and ovariectomized (OVX) rats treated with or without estradiol,
      tamoxifen, or <span class="smallcap">l</span>-arginine. Bolus isoprenaline (0.03
      8.0 micromol) elicited dose-dependent renal vasodilations; female preparations
      were more sensitive (smaller ED50) to isoprenaline-induced vasodilation than were
      male preparations. Infusion of nicotine (500 micromol/L) reduced isoprenaline
      vasodilations in the 2 sexes and abolished male-female differences in
      isoprenaline responses. <span class="smallcap">l</span>-NNA reduced isoprenaline
      vasodilations in proestrus but not in male preparations. Also, in the presence of
      <span class="smallcap">l</span>-NNA, nicotine caused no attenuation of
      isoprenaline vasodilations in proestrus preparations. Renal responses to
      isoprenaline together with the attenuation of these responses by nicotine were
      reduced by OVX and restored to near-proestrus levels after supplementation with
      estradiol, the estrogen receptor modulator tamoxifen, or <span
      class="smallcap">l</span>-arginine. In diestrus rats, which exhibited reduced
      plasma estradiol, nicotine caused less attenuation of isoprenaline vasodilations.
      We conclude that impairment of estrogen-NOS signaling constitutes a possible
      cellular mechanism for the detrimental effect of nicotine on isoprenaline
      vasodilations in female rats. The mechanism of the nicotine-induced attenuation
      of isoprenaline vasodilation in male kidneys, which is NOS-independent, remains
      to be elucidated.

PMID- 19767878
TI  - Rosiglitazone inhibits high glucose-induced apoptosis in human umbilical vein
      endothelial cells through the PI3K/Akt/eNOS pathway.
AB  - Previous studies have shown that the phosphatidylinositol 3-kinase / Akt /
      endothelial nitric oxide synthase / NO (PI3K/Akt/eNOS/NO) pathway is involved in
      high glucose-induced endothelial cell apoptosis and rosiglitazone has a
      protective effect on endothelium. In the present study, we investigated the
      antiapoptotic effect of rosiglitazone on human umbilical vein endothelial cells
      (HUVECs) exposed to high glucose and explored its possible mechanism. Treatment
      of high glucose (33 mmol/L) for 48 h significantly induced the apoptosis of
      HUVECs, concomitantly with increased caspase-3 activity. High glucose treatment
      also decreased Akt and eNOS phosphorylation levels with subsequent NO production.
      All these alterations induced by high glucose were attenuated by rosiglitazone (1
      micromol/L). Interestingly, the antiapoptotic effect of rosiglitazone was
      inhibited by PI3K inhibitor (LY294002, wortmannin) or eNOS inhibitor NG-<span
      class="smallcap">l</span>-nitro-arginine methyl ester (<span
      class="smallcap">l</span>-NAME). The reverse effects of rosiglitazone on
      phosphorylation of Akt and eNOS with subsequent NO production were also inhibited
      by LY294002, wortmannin or <span class="smallcap">l</span>-NAME, respectively.
      These findings suggest that rosiglitazone inhibits high glucose-induced apoptosis
      in HUVECs through the PI3K/Akt/eNOS pathway.

PMID- 19767879
TI  - Sildenafil decreased cardiac cell apoptosis in diabetic mice: reduction of
      oxidative stress as a possible mechanism.
AB  - Oxidative stress plays a dominant role in the pathogenesis of cardiac cell
      apoptosis in diabetic patients. Sildenafil has been demonstrated to have
      antioxidant effects. In this study, the effects of sildenafil on diabetes-induced
      cardiac cell apoptosis and the antioxidant status of diabetic mouse hearts were
      investigated. Diabetic mice showed lower body weight gains and heart weights
      compared with control mice, and sildenafil treatment did not increase these
      parameters in diabetic mice. Although apoptotic rates, caspase-3 enzyme activity,
      and malondialdehyde levels were significantly higher in diabetic mouse hearts
      than in controls, they were reduced in diabetic mice after sildenafil treatment.
      At the end of the first week, we observed no significant differences in
      antioxidant enzyme activities (CAT, GSH-Px, and SOD) in diabetic and control
      groups, whereas at the end of the second week of sildenafil treatment,
      antioxidant enzyme activities were higher in the diabetic group. In conclusion,
      our study indicated that sildenafil was beneficial to hearts of diabetic mice by
      reducing cardiac cell apoptosis, partially because of its antioxidant effects in
      the heart.

PMID- 19767880
TI  - Baroreflex sensitivity is reduced in obese normotensive children and adolescents.
AB  - Obesity is associated with autonomic nervous system dysfunction. The aim of the
      study was to evaluate baroreflex sensitivity, an indicator of autonomic nervous
      function, in 20 obese children and adolescents in comparison with 20 age- and sex
      matched nonobese subjects. All subjects were examined in the supine position over
      a period of 50 min. Systolic blood pressure (SBP) and RR intervals were monitored
      continuously. Baroreflex sensitivity was assessed by cross-spectral analysis of
      SBP and RR interval oscillations (BRS index) and SBP and heart rate oscillations
      (BRSf index) within the low frequency range (0.04-0.15 Hz). Sensitivity was
      determined in 3 time intervals of 3 min each to evaluate changes during rest. The
      BRS index was significantly lower in obese children and adolescents than in the
      nonobese control group (p = 0.002). Significant changes in the BRS index over
      time (p = 0.004) were found only in nonobese subjects. In contrast, the BRSf
      index increased over time in both groups (p = 0.01), and no significant between
      group difference was detected. In conclusion, obese children and adolescents show
      decreased resting baroreflex sensitivity with less variation compared with
      nonobese subjects. The BRS and BRSf indices appear to be only partially
      correlated.

PMID- 19767881
TI  - Epileptic seizure-induced hypertension and its prevention by calcium channel
      blockers: a real-time study in conscious telemetered rats.
AB  - Epileptic seizures are accompanied by changes in autonomic function that in turn
      influence the cardiovascular system (hypertension and bradyarrhythmia). We have
      studied possible cardioprotective activity (during the ictal state in conscious
      animals) of valproic acid, nifedipine, and verapamil, alone and in combination,
      during pentylenetetrazole (PTZ)-induced seizures. Telemetry system was used for
      recording EEG, blood pressure, and heart rate in conscious, freely moving rats
      during seizures. We observed that PTZ-induced seizures were accompanied by
      hypertension and bradyarrhythmia. Pretreatment with valproic acid did not block
      seizure-induced hypertension and bradyarrhythmia. Nifedipine alone and in
      combination with valproic acid blocked seizure-induced hypertension and
      bradyarrhythmia significantly. We also observed that pretreatment with verapamil
      alone and in combination with valproic acid did not block seizure-induced
      hypertension and bradyarrhythmia significantly. Our results suggest that
      pretreatment with nifedipine alone or in combination with valproic acid provides
      protection against seizure-induced hypertension and bradyarrhythmia.

PMID- 19767882
TI  - Cerebral blood flow regulation by nitric oxide in neurological disorders.
AB  - There has been a rapid increase in the amount of information on the physiological
      and pathophysiological roles of nitric oxide (NO) in the brain. This molecule,
      which is formed by the constitutive isoforms of NO synthase, endothelial (eNOS)
      and neuronal (nNOS), plays an obligatory role in the regulation of cerebral blood
      flow and cell viability and in the protection of nerve cells or fibres against
      pathogenic factors associated with Alzheimer's disease, Huntington's disease,
      seizures, and migraine. Cerebral blood flow is impaired by decreased formation of
      NO from endothelial cells, autonomic nitrergic nerves, or brain neurons and also
      by increased production of reactive oxygen species (ROS). The NO-ROS interaction
      is an important topic in discussing blood flow and cell viability in the brain.
      Excessive production of NO by inducible NOS (iNOS) and nNOS in the brain
      participates in neurotoxicity. Recent studies on brain circulation have provided
      useful information about the involvement of impaired NO availability or
      uncontrolled NO production in cerebral pathogenesis, including Alzheimer's
      disease, seizures, vascular headaches, and inflammatory disorders. Insight into
      the role of NO in the brain will contribute to our better understanding of
      cerebral hemodynamic dysfunction and will aid in developing novel therapeutic
      measures in diseases of the central nervous system.

PMID- 19767883
TI  - Rho-kinase inhibitors Y-27632 and fasudil prevent agonist-induced vasospasm in
      human radial artery.
AB  - Radial artery (RA) vasospasm remains a potential cause of early graft failure
      after coronary artery bypass graft surgery, despite pretreatment with alpha
      adrenergic or calcium channel blockers. Our aim was to investigate the mechanism
      of the vasorelaxant effects of Rho-kinase inhibitors (Y-27632 and fasudil) on the
      human RA. Segments were obtained from 30 patients undergoing coronary artery
      bypass graft and were divided into 3-4 mm vascular rings. The rings were
      stimulated with 10(-5) mol/L phenylephrine (PE) by using the isolated tissue bath
      technique and were relaxed with 10(-6) mol/L acetylcholine. Relaxation responses
      were recorded for Y-27632 (10(-9)-10(-4) mol/L), fasudil (10(-9)-10(-4) mol/L),
      and sodium nitroprusside (SNP) (10(-9)-10(-5) mol/L). Y-27632 and fasudil
      relaxation responses were repeated in either N(G)-nitro-L-arginine (L-NNA), which
      is a specific endothelial nitric oxide synthase inhibitor, or 1H
      [1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), which is a guanylate cyclase
      inhibitor. SNP relaxation responses were repeated in 10(-8) mol/L Y-27632 and 10(
      8) mol/L fasudil. Y-27632 and fasudil caused concentration-dependent
      vasorelaxation in RA rings precontracted with PE, and maximal relaxation (100%)
      was recorded at the highest concentration used (10(-4) mol/L). The vasorelaxant
      effects of Y-27632 and fasudil were significantly reduced in the presence of L
      NNA and ODQ, and the pD2 values of Y-27632 and fasudil were not changed. The
      vasorelaxant effects of SNP were significantly increased in the presence of Y
      27632 and fasudil, and the pD(2) values of SNP were not changed. These findings
      indicate that Y-27632 and fasudil caused concentration-dependent vasorelaxation
      in the RA rings. Because this effect was decreased in a dose-dependent manner by
      L-NNA and ODQ, the relaxant effects of Y-27632 and fasudil could be due to
      stimulation by nitric oxide that is being released. Rho-kinase inhibitors may
      have an important role in preventing vasospasm in arterial grafts used for
      coronary artery surgery.

PMID- 19767884
TI  - Quantification of the relationship between glycemia and beta-cell mass adaptation
      in vivo.
AB  - Beta-cell mass dynamics play an important role in the adaptation to obesity, as
      well as in the pathogenesis of type 2 diabetes. Here we used a 24-hour modified
      hyperglycemic clamp protocol to investigate the effect of increasing glucose
      concentrations (15, 20, 25, or 35 mmol/L) on beta-cell mass and rates of beta
      cell replication, death, and neogenesis in 6-week-old Sprague Dawley rats (n =
      40). During the first 4 h of glucose infusion, plasma insulin levels rose to an
      approximate steady state in each group, but by the end of 24 h, there was no
      difference in insulin levels between any of the groups. There was also no
      difference in beta-cell mass between groups. Mean beta-cell replication rates
      displayed a linear relationship to mean plasma glucose levels in all
      hyperglycemic animals (r(2) = 0.98, p < 0.05). Relative to the uninfused basal
      control animals, replication rates were significantly reduced in the 15 mmol/L
      glucose group. The percentage of TUNEL-positive beta-cells was not different
      between groups. There was also no significant difference in markers of
      neogenesis. Thus, these data demonstrate that hyperglycemia for 24 h had no
      effect on beta-cell mass, death, or neogenesis in 6-week-old Sprague Dawley rats.
      We demonstrate a linear relationship, however, between hyperglycemia and beta
      cell replication rates in vivo.

PMID- 19767885
TI  - Wet and dry extraction of coconut oil: impact on lipid metabolic and antioxidant
      status in cholesterol coadministered rats.
AB  - Because coconut oil extracted by wet process (virgin coconut oil, VCO) is gaining
      popularity among consumers, this study was conducted to evaluate VCO compared
      with coconut oil extracted by dry process (copra oil, CO) for their influence on
      lipid parameters, lipid peroxidation, and antioxidant status in rats
      coadministered with cholesterol. VCO, CO, and cholesterol were fed in a semi
      synthetic diet to 24 male Sprague-Dawley rats for 45 days. After the experimental
      period, lipid and lipid peroxide levels and antioxidant enzyme activities were
      observed. Chemical composition and antioxidant properties of the polyphenolic
      fraction from VCO and CO were also analyzed. The results showed that lipid and
      lipid peroxide levels were lower in VCO-fed animals than in animals fed either CO
      or cholesterol alone. Antioxidant enzyme activities in VCO-fed animals were
      comparable with those in control animals. Although the fatty acid profiles of
      both oils were similar, a significantly higher level of unsaponifiable components
      was observed in VCO. Polyphenols from VCO also showed significant radical
      scavenging activity compared with those from CO. This study clearly indicates the
      potential benefits of VCO over CO in maintaining lipid metabolism and antioxidant
      status. These effects may be attributed in part to the presence of biologically
      active minor unsaponifiable components.

PMID- 19767886
TI  - Effects of cadmium on cardiac metallothionein induction and ischemia-reperfusion
      injury in rats.
AB  - Myocardial ischemia-reperfusion injury is associated with an imbalance between
      the formation and the scavenging of reactive oxygen species. In this context, the
      protective role of the antioxidant metallothionein, a thiol-rich protein that is
      induced in different organs in response to heavy metals and oxidative conditions,
      has mainly been investigated in metallothionein-knockout mice or metallothionein
      overexpressing mice. The aim of this study was to evaluate whether the
      administration of cadmium has a protective effect against cardiac ischemia
      reperfusion injury and whether this is associated with induction of in vivo
      cardiac metallothionein. Forty-eight hours after an injection of 0, 1, or 2 mg/kg
      cadmium, isolated perfused rat hearts were submitted to 30 min of total global
      ischemia and 30 min of reperfusion. The ischemia-reperfusion sequence was
      associated with a significant decrease in cardiac metallothionein levels.
      Pretreatment with cadmium at a dose of 2 mg/kg (i) prevented this decrease and
      (ii) improved the postischemic recuperation of the coronary flow, the ventricular
      developed pressure, and therefore, the global postischemic functional recovery.
      These results showed that pretreatment of rats with 2 mg/kg cadmium induced
      cardioprotection against ischemia-reperfusion injuries, perhaps through an in
      vivo metallothionein induction that may be related to a metal activation of
      antioxidant systems.

PMID- 19767887
TI  - Modulatory action of potassium channel openers on field potential and histamine
      release from rat peritoneal mast cells.
AB  - To determine whether changes in membrane potential affect the extent of mast cell
      degranulation, compound 48/80 was added to rat peritoneal mast cell suspensions
      in the absence or presence of potassium channel openers (KCOs). Changes were
      compared between the field potential (FP) and the amount of histamine released.
      The results demonstrated that (i) the onset and duration of FP, which reflects
      the hyperpolarizing nature of the response, increased as the concentration of
      compound 48/80 increased; (ii) both FP and the amount of histamine released
      increased as the concentration of compound 48/80 increased; (iii) although both
      KCOs (SDZ PCO400, a benzopyran derivative, and P1060, a cyanoguanidine
      derivative) potentiated compound 48/80-induced increases in FP and histamine
      release, without compound 48/80, they had no effect on either parameter; (iv)
      both glibenclamide and charybdotoxin significantly attenuated the compound 48/80
      induced increase in FP; and (v) glibenclamide was able to attenuate the KCO
      induced potentiation of FP. The results show that drugs presumably causing
      hyperpolarization can affect histamine release from rat peritoneal mast cells.
      The effect of KCOs on compound 48/80-induced response appears to be potentiation
      in nature rather than synergism. It is possible that KCO hyperpolarizes the cell
      membrane, enhances Ca2+ influx, and thus increases histamine release. As such,
      selective blockers of K+ channels may be useful for the treatment of
      immunological disorders.

PMID- 19767888
TI  - Cardioprotective roles of aged garlic extract, grape seed proanthocyanidin, and
      hazelnut on doxorubicin-induced cardiotoxicity.
AB  - Doxorubicin (DXR) is a chemotherapeutic agent used effectively in the treatment
      of several childhood malignancies. During treatment, cardiotoxicity caused by
      cell damage due to the free oxygen radicals that are generated is a major
      limiting factor. This study was undertaken to determine whether DXR-induced
      cardiotoxicity could be prevented by natural foods with antioxidant properties
      such as aged garlic extract (AGEX), grape seed proanthocyanidin (PA), and
      hazelnut. Wistar albino male rats were assigned randomly to 9 groups each
      consisting of 15 rats. AGEX, PA, and hazelnut groups received these antioxidants
      in addition to their standard rat diet. They were also treated with cumulative
      intraperitoneal (i.p.) injections according to 2 different regimens: either a
      high-dose of 15 mg/kg DXR (3.75 mg/kg per week for 4 weeks) or a low-dose of 7.5
      mg/kg DXR (1.875 mg/kg per week for 4 weeks). The control group received i.p.
      0.9% saline. AGEX, PA, or hazelnut supplements were given orally to the groups
      for a 6-week period starting 1 week before the DXR treatment and ending 1 week
      after the treatment. One week after the last DXR injection, heart tissue samples
      were analyzed to determine malondialdehyde (MDA), superoxide dismutase (SOD),
      catalase (CAT), and xanthine oxidase (XO) levels, and serum samples were taken
      for creatine kinase (CK). There were no significant changes in MDA levels among
      the control, DXR-treated groups, or supplemented groups that received additional
      natural antioxidant foods. SOD enzyme levels were decreased in rats treated with
      DXR. PA prevented the decrease at low doses of DXR. DXR treatment decreased CAT
      enzyme levels, but additional PA and hazelnut consumption increased these levels
      at low cumulative doses. XO enzyme levels were decreased in AGEX and hazelnut
      groups, but PA prevented the decrease. CK levels were elevated after DXR
      administration, indicating myocardial injury, but PA significantly reversed this.
      Although there were no differences histopathologically between AGEX, PA, and
      hazelnut groups, the protective effects of AGEX and PA were evident in electron
      microscopy. In conclusion, the positive effects of natural antioxidant foods on
      the prevention of DXR-induced cardiac injury could not be clearly shown on the
      basis of antioxidant enzymes. However, the electron microscopic changes clearly
      demonstrated the protective effects of AGEX and PA. The supplementation of these
      antioxidant foods over longer periods may show more definitive results. Human
      studies with different doses are needed to evaluate the effects of these foods on
      the human heart.

PMID- 19767889
TI  - Myocardial remodelling induced by repeated low doses of isoproterenol.
AB  - In the present work, the effect of isoproterenol on the electrical properties of
      the rat heart and on the cytoarchitecture of the surviving cardiomyocytes was
      studied. Myocardial remodelling was induced by the daily administration of 5
      mg/kg isoproterenol (Iso) for 7 days. Administration resulted in a significant
      increase (52%) in the ratio of left ventricular weight to body weight. ECG
      voltage criteria confirmed the presence of left ventricular hypertrophy. QT
      interval prolongation by 23% and 58% was found in Iso rats and in the
      corresponding isolated hearts, respectively. Spontaneously beating Iso hearts had
      a higher incidence of dysrhythmias. The surviving cardiomyocytes showed an
      irregular shape with cytoplasmic processes rich in ribosomes and rough
      endoplasmic reticulum. In these regions, myofibril disorganization and
      mitochondrial fission were observed. A greatly increased incidence of caveolae
      was seen in the plasma membrane and in the mouth of t-tubules. The membranes of t
      tubules showed vesiculation, especially near the dyads. Repeated administration
      of isoproterenol led to hypertrophy, characterized by the existence of myocytes
      with simultaneous signs of both mature and postnatally developing cardiomyocytes.
      Structural microheterogeneities at the level of individual cells may represent
      one of the factors leading to electrical imbalance in the myocardial tissue
      remodelled by isoproterenol.

PMID- 19767890
TI  - Relationship between bruchid resistance and seed mass in mungbean based on QTL
      analysis.
AB  - Bruchids (Coleoptera: Bruchidae) can cause serious damage to mungbean and several
      other leguminous crops and there is a strong association between small seed size
      and bruchid resistance. In investigating the feasibility of breeding large-seeded
      cultivars with high levels of bruchid resistance, we studied the relationship
      between these two traits by QTL analysis. A major locus conferring resistance to
      Callosobruchus chinensis was identified from a wild mungbean genotype, 'ACC41'
      (belonging to Vigna radiata var. sublobata), collected in Australia. The
      proportion of the C. chinensis resistance response that could be attributed to
      this single QTL varied among four different resistance assays. The highest value
      reached was 98.5%, suggesting that bruchid resistance in this genotype is likely
      conditioned by this single locus. The QTL was robust and its detection was not
      affected by the use of different sources of the insect, different lengths and
      conditions of seed storage, or different bruchid resistance assay methods. This
      bruchid resistance QTL was coincident with one of the loci conferring seed mass
      detected from the three seed sources produced in Australia. However, such a co
      location was not detected for the seed source produced in China. Covariance
      analysis revealed a complex relationship between seed mass and bruchid
      resistance. Nevertheless, the effect of the bruchid resistance QTL remained
      highly significant for all four assays after the effect of seed mass was
      accounted for. These results, together with the relationship between the bruchid
      resistance QTL identified in this study and a second one detected previously in a
      wild mungbean genotype from Madagascar, are discussed.

PMID- 19767891
TI  - Histone genes of the razor clam Solen marginatus unveil new aspects of linker
      histone evolution in protostomes.
AB  - The association of DNA with histones results in a nucleoprotein complex called
      chromatin that consists of repetitive nucleosomal subunits. Nucleosomes are
      joined together in the chromatin fiber by short stretches of linker DNA that
      interact with a wide diversity of linker H1 histones involved in chromatin
      compaction and dynamics. Although the long-term evolution of the H1 family has
      been the subject of different studies during the last 5 years, the lack of
      molecular data on replication-independent (RI) H1 variants from protostomes has
      been hampering attempts to complete the evolutionary picture of this histone
      family in eukaryotes, especially as it pertains to the functional specialization
      they impart to the chromatin structure in members of this bilaterian lineage. In
      an attempt to fill this gap, the present work characterizes the histone gene
      complement from the razor clam Solen marginatus. Molecular evolutionary analyses
      reveal that the H1 gene from this organism represents one of the few protostome
      RI H1 genes known to date, a notion which is further supported by its location
      within the monophyletic group encompassing the RI H1 variants in the overall
      phylogeny of eukaryotic H1 proteins. Although the detailed characterization of
      the nucleotide substitution patterns in RI H1 variants agrees with the model of
      birth-and-death evolution under strong purifying selection, maximum-likelihood
      approaches unveil the presence of adaptive selection during at least part of the
      evolutionary differentiation between protostomes and deuterostomes. The presence
      of increased levels of specialization in RI H1 proteins from deuterostomes as
      well as the significant differences observed in electrostatic properties between
      protostome and deuterostome RI H1s represent novel and important preliminary
      results for future studies of the functional differentiation of this histone H1
      lineage across bilaterians.

PMID- 19767892
TI  - Mapping of STS markers obtained from oat resistance gene analog sequences.
AB  - Two previously isolated resistance gene analogs (RGAs) of oat have been located
      as RFLPs in the reference map of Avena byzantina 'Kanota' x Avena sativa 'Ogle'
      in regions either homologous or homoeologous to loci for resistance to Puccinia
      coronata, the causal agent of crown rust. In this study, the RGAs were mapped in
      two recombinant inbred line (RIL) populations that segregate for crown rust
      resistance: the diploid Avena strigosa x Avena wiestii RIL population (Asw),
      which has been used for mapping the complex locus PcA, and the hexaploid MN841801
      1 x Noble-2 RIL population (MN), in which QTLs have been located. To obtain
      single-locus markers, RGAs were converted to sequence tagged site (STS) markers
      using a procedure involving extension of the original RGA sequence lengths by PCR
      genome walking, amplification and cloning of the parental fragments, and
      identification of single nucleotide polymorphisms. The procedure successfully
      obtained STSs from different members of the L7M2 family of sequences, the initial
      NBS of which have nucleotide similarities of >83%. However, for RGA III2.18, the
      parental lines were not polymorphic for the STSs assayed. A sequence
      characterized amplified region (SCAR) marker with features of an RGA had been
      previously identified for gene Pc94. This marker was also mapped in the above RIL
      populations. Markers based on RGA L7M2 co-localized with markers defining the QTL
      Prq1a in linkage group MN3, and were located 15.2 cM from PcA in linkage group
      AswAC. The SCAR marker for Pc94 was also located in the QTL Prq1a but at 39.5 cM
      from PcA in AswAC, indicating that the NBS-LRR sequence represented by this
      marker is not related to PcA. L7M2 was also excluded as a member of the PcA
      cluster, although it could be an appropriate marker for the Prq1a cluster if
      chromosome rearrangements are postulated.

PMID- 19767893
TI  - Comparative analysis of the Brassica oleracea genetic map and the Arabidopsis
      thaliana genome.
AB  - We further investigated genome macrosynteny for Brassica species and Arabidopsis
      thaliana. This work aimed at comparative map construction for B. oleracea and A.
      thaliana chromosomes based on 160 known A. thaliana probes: 147 expressed
      sequence tags (ESTs) and 13 full-length cDNA clones. Based on an in silico study
      of the A. thaliana genome, most of the selected ESTs (83%) represented unique or
      low-copy genes. We identified conserved segments by the visual inspection of
      comparative data with a priori assumptions, and established their significance
      with the LineUp algorithm. Evaluation of the number of B. oleracea gene copies
      per A. thaliana EST revealed a fixed upward trend. We established a segregation
      distortion pattern for all genetic loci, with particular consideration of the
      type of selection (gametic or zygotic), and discuss its possible impact on
      genetic map construction. Consistent with previous reports, we found evidence for
      numerous chromosome rearrangements and the genome fragment replication of B.
      oleracea that have taken place since the divergence of the two species. Also, we
      found that over 54% of the B. oleracea genome is covered by 24 segments conserved
      with the A. thaliana genome. The average conserved segment is composed of 5 loci
      covering 19.3 cM in the B. oleracea genetic map and 2.42 Mb in the A. thaliana
      physical map. We have also attempted to use a unified system of conserved blocks
      (previously described) to verify our results and perform a comprehensive
      comparison with other Brassica species.

PMID- 19767894
TI  - Genetic differentiation of wild and cultivated populations: diversity of Coffea
      canephora Pierre in Uganda.
AB  - Coffea canephora Pierre ex Frohener is a perennial plant originated from Africa.
      Two main groups, Guinean and Congolese, have already been identified within this
      species. They correspond to main refugia in western and central Africa. In this
      paper we present the analysis of a region that has not yet been studied, Uganda.
      Two wild, one feral (once cultivated but abandoned for many years), and two
      cultivated populations of C. canephora from Uganda were evaluated using 24
      microsatellite markers. Basic diversity, dissimilarity and genetic distances
      between individuals, genetic differentiation between populations, and structure
      within populations were analysed. Expected heterozygosity was high for wild
      compartments (0.48 to 0.54) and for cultivated and feral ones (0.57 to 0.59),
      with the number of private alleles ranging from 12 for cultivated genotypes to 37
      for a wild compartment. The Ugandan samples show significant population
      structuring. We compared the Ugandan populations with a representative sample of
      known genetic diversity groups within the species using 18 markers. Coffea
      canephora of Ugandan origin was found to be genetically different from previously
      identified diversity groups, implying that it forms another diversity group
      within the species. Given its large distribution and extremely recent
      domestication, C. canephora can be used to understand the effect of refugia
      colonization on genetic diversity.

PMID- 19767895
TI  - Characterization of Salt Overly Sensitive 1 (SOS1) gene homoeologs in quinoa
      (Chenopodium quinoa Willd.).
AB  - Salt tolerance is an agronomically important trait that affects plant species
      around the globe. The Salt Overly Sensitive 1 (SOS1) gene encodes a plasma
      membrane Na+/H+ antiporter that plays an important role in germination and growth
      of plants in saline environments. Quinoa (Chenopodium quinoa Willd.) is a
      halophytic, allotetraploid grain crop of the family Amaranthaceae with impressive
      nutritional content and an increasing worldwide market. Many quinoa varieties
      have considerable salt tolerance, and research suggests quinoa may utilize novel
      mechanisms to confer salt tolerance. Here we report the cloning and
      characterization of two homoeologous SOS1 loci (cqSOS1A and cqSOS1B) from C.
      quinoa, including full-length cDNA sequences, genomic sequences, relative
      expression levels, fluorescent in situ hybridization (FISH) analysis, and a
      phylogenetic analysis of SOS1 genes from 13 plant taxa. The cqSOS1A and cqSOS1B
      genes each span 23 exons spread over 3477 bp and 3486 bp of coding sequence,
      respectively. These sequences share a high level of similarity with SOS1 homologs
      of other species and contain two conserved domains, a Nhap cation-antiporter
      domain and a cyclic-nucleotide binding domain. Genomic sequence analysis of two
      BAC clones (98 357 bp and 132 770 bp) containing the homoeologous SOS1 genes
      suggests possible conservation of synteny across the C. quinoa sub-genomes. This
      report represents the first molecular characterization of salt-tolerance genes in
      a halophytic species in the Amaranthaceae as well as the first comparative
      analysis of coding and non-coding DNA sequences of the two homoeologous genomes
      of C. quinoa.

PMID- 19767896
TI  - Isolation and characterization of the rye Waxy gene.
AB  - Complete genomic and cDNA sequences of the Waxy gene encoding granule-bound
      starch synthase I (GBSSI) were isolated from the rye genome and characterized.
      The full-length rye Waxy genomic DNA and cDNA are 2767 bp and 1815 bp,
      respectively. The genomic sequence has 11 exons interrupted by 10 introns. The
      rye Waxy gene is GC-rich, with a higher GC frequency in the coding region,
      especially in the third position of the codons. Exon regions of the rye Waxy gene
      are more conserved than intron regions when compared with the homologous
      sequences of other cereals. The mature rye GBSSI proteins share more than 95%
      sequence identity with their homologs in wheat and barley. A phylogenetic tree
      based on sequence comparisons of available plant GBSSI proteins shows the
      evolutionary relationship among Waxy genes from rye and other plant genomes. The
      identification of the rye Waxy gene will enable the manipulation of starch
      metabolism in rye and triticale.

PMID- 19767897
TI  - EST-SSR markers derived from an elite barley cultivar (Hordeum vulgare L.
      'Morex'): polymorphism and genetic marker potential.
AB  - Microsatellites or simple sequence repeats have become the markers of choice for
      marker-assisted selection because of their low template DNA requirement, high
      reproducibility, and high level of polymorphism. This study investigated a new
      set of barley (Hordeum vulgare L.) EST-derived SSR markers designed to target
      gene sequences expressed during grain development, as they are more likely to be
      important in determining grain quality. The EST sequences (HVSMEh and HVSMEi)
      were derived from cDNA libraries of the elite six-rowed cultivar Morex, made from
      spikes harvested at 5 to 45 days after pollination. Approximately half of the 110
      SSR markers derived from the ESTs were polymorphic in a panel of 8 diverse barley
      genotypes, with PIC values between 0.19 and 0.79. Twenty of the new markers were
      mapped to chromosomal locations using 2 doubled haploid populations. To
      demonstrate marker potential, quantitative trait locus (QTL) analyses were
      carried out with phenotypic data on wort beta-glucan content and beta-glucanase
      activity, two traits with a long history of genetic studies. Most of the EST-SSR
      markers mapped to within 10 cM of the cellulose synthase (HvCesA) and cellulose
      synthase-like (HvCslF) genes, which provides highly informative functional
      markers for tracking these genes in breeding programs. It was also observed that
      on any given chromosome, the QTL for beta-glucan content and beta-glucanase
      activity were rarely coincident but tended to occur in adjacent intervals along
      chromosomal regions, which agreed with their independent genetic basis; the
      adjacent localization may be important for coordination of cell wall degradation
      during germination and malting.

PMID- 19767898
TI  - Identification of nutrient and physical seed trait QTL in the model legume Lotus
      japonicus.
AB  - Legume seeds have the potential to provide a significant portion of essential
      micronutrients to the human diet. To identify the genetic basis for seed nutrient
      density, quantitative trait locus (QTL) analysis was conducted with the
      Miyakojima MG-20 x Gifu B-129 recombinant inbred population from the model legume
      Lotus japonicus. This population was grown to seed under greenhouse conditions in
      2006 and 2007. Phenotypic data were collected for seed calcium (Ca), copper (Cu),
      iron (Fe), potassium (K), magnesium (Mg), manganese (Mn), phosphorus (P), sulfur
      (S), and zinc (Zn) concentrations and content. Data for physical seed traits
      (average seed mass and seed-pod allocation values) were also collected. Based on
      these phenotypic data, QTL analyses identified 103 QTL linked to 55 different
      molecular markers. Transgressive segregation, identified within this recombinant
      inbred population for both seed nutrient and physical traits, suggests new
      allelic combinations are available for agronomic trait improvement. QTL co
      localization was also seen, suggesting that common transport processes might
      contribute to seed nutrient loading. Identification of loci involved in seed
      mineral density can be an important first step in identifying the genetic factors
      and, consequently, the physiological processes involved in mineral distribution
      to developing seeds. Longer term research efforts will focus on facilitating
      agronomic breeding efforts through ortholog identification in related crop
      legumes.

PMID- 19767899
TI  - Relationships of Campanian olive cultivars: comparative analysis of molecular and
      phenotypic data.
AB  - Estimation of the genetic relatedness of traditional olive cultivars with genetic
      markers and phenotypic data enables progress in plant breeding, management of
      genetic resources, and protection of both breeders' rights and certified premium
      products. We used amplified fragment length polymorphisms (AFLPs), simple
      sequence repeats (SSRs), and quantitative and qualitative morphological traits,
      including characteristics recommended for variety registration, to study genetic
      diversity and relationships in the olive at different levels. The 14 varieties
      analyzed, which are used for the production of Protected Denomination of Origin
      extra-virgin olive oil, represent the most important cultivars in the Campania
      region of Italy and typify a regional diversity characteristic of traditional
      olive cultivation. The genetic distances obtained with the two DNA marker systems
      were significantly correlated, as were those obtained by quantitative and
      qualitative traits. A lower but significant correlation was also observed between
      distances based on molecular markers and quantitative traits, but qualitative
      traits, even if sampled in high numbers, failed to describe the pattern of
      molecular similarity. Our data imply that the type and the number of phenotypic
      traits scored can greatly influence the outcome of the analysis, and care should
      be taken when qualitative and quantitative data are combined. Furthermore, the
      data indicate that the two molecular marker systems are useful for investigating
      genetic relationships, but they may also be used to complement and assist the
      traditional registration of varieties. We propose that since the information
      provided by molecular and morphological marker systems in olive is different,
      they should serve different purposes.

PMID- 19767900
TI  - Localisation of quantitative trait loci for quality attributes in a doubled
      haploid population of wheat (Triticum aestivum L.).
AB  - Selection of wheat germplasm for a range of quality traits has been a challenging
      exercise because of the cost of testing, the variation within testing data, and a
      poor understanding of the underlying genetics. The objective of this study was to
      identify quantitative trait loci (QTLs) underlying quality traits in wheat. A
      doubled haploid population comprising 190 lines from Chara/WW2449 was grown in
      two different environments and evaluated for various quality traits. A molecular
      map comprising 362 markers based upon simple sequence repeat, sequence tagged
      microsatellite, glutenin, and DArT loci was constructed and subsequently
      exploited to identify QTLs using a whole-genome approach. Fifteen QTLs that were
      consistent in the two different environments were identified for thousand kernel
      mass, grain protein content, milling yield, flour protein content, flour colour,
      flour water absorption, dough development time, dough strength (extensograph
      height and resistance at 5 cm), and dough extensibility (extensograph length)
      using the whole genome average interval mapping approach. The amount of genetic
      variation explained by individual QTLs ranged from 3% to 49%. A number of QTLs
      associated with dough strength, dough extensibility, dough development time, and
      flour water absorption were located close to the glutenin Glu-B1 locus on
      chromosome 1B. Identification of the chromosomal location and effect of the QTLs
      influencing wheat quality may hasten the development of superior wheats for
      target markets via marker-assisted selection.

PMID- 19767901
TI  - Enrichment of a papaya high-density genetic map with AFLP markers.
AB  - A high-density genetic linkage map of papaya, previously developed using an F2
      mapping population derived from the intraspecific cross AU9 x SunUp, was enriched
      with AFLP markers. The comprehensive genetic map presented here spans 945.2 cM
      and covers 9 major and 5 minor linkage groups containing 712 SSR, 277 AFLP, and 1
      morphological markers. The average marker density for the 9 major linkage groups
      is 0.9 cM between adjacent markers, and the total number of gaps >5 cM was
      reduced from 48 to 27 in the current map. AFLPs generated by EcoRI/MseI primer
      combinations were distributed throughout the 14 linkage groups and resulted in
      several large locus order rearrangements within the 9 major linkage groups.
      Integration of AFLP markers provided tighter linkage association between loci,
      leading to a reduction in map distance on LGs 1, 2, and 4, which were inflated in
      the previous map, and correction of the marker order on LG8. Suppression of
      recombination in the male-specific Y region (MSY) of LG1 is further validated by
      the addition of 27 sex co-segregating AFLP markers. A large region of distorted
      segregation surrounding the MSY spans 54.4 cM and represents approximately 71% of
      the linkage group. This comprehensive high-density genetic map provides a
      framework for mapping quantitative trait loci and for fine mapping as well as for
      comparative genomic studies of crop plant development and evolution.

PMID- 19767902
TI  - EST mining for structure and expression of genes in the region of the wheat high
      molecular-weight glutenin loci.
AB  - An in-depth analysis was carried out with expressed sequence tags (ESTs) for
      genes in and near the HMW-GS loci. Considerations for using ESTs are discussed,
      including the occurrence of chimeric and aberrant HMW-GS ESTs. Complete gene
      sequences demonstrated the feasibility of constructing accurate full-length
      coding regions from EST assemblies and found, or supported, errors in several
      previously reported HMW-GS gene sequences. New complete HMW-GS gene sequences are
      reported for the cultivars Chinese Spring and Glenlea. The Ay subunit gene, which
      is considered null in cultivated wheats, was shown to transcribe in at least two
      germplasms. Analyses support the conclusion that of the five known genes within
      this genomic region, the two HMW-GS genes and the globulin gene are highly
      expressed. The other two genes, encoding a receptor kinase and a protein kinase,
      have one and no identifiable wheat EST, respectively, although ESTs are found for
      the orthologous genes in barley. The ESTs of all five genes within the HMW-GS
      region are either definitely associated with the endosperm or possibly originate
      from imbibed seed, suggesting the four distinct gene classes in this region are
      part of a seed or endosperm chromatin domain. EST resources were also used to
      determine relative abundance of ESTs for all classes of wheat prolamines and
      indicated differential levels of expression both among germplasms and among the
      three genomes of hexaploid wheats.

PMID- 19767903
TI  - Utility of intradermal blood smear in the detection of asymptomatic malaria
      parasitaemia in pregnancy.
AB  - OBJECTIVES: We evaluated the usefulness of intradermal smear microscopy (IDS) in
      the detection of asymptomatic malaria parasitaemia in pregnancy. Peripheral
      venous blood (PVB) served as control. The preference for the collection technique
      of dermal blood was also assessed. PATIENTS AND METHODS: One hundred and fifty
      (150) asymptomatic women were recruited. They had both intradermal smear and
      peripheral venous blood smear were made for all patients. Measures of test
      validity included sensitivity, specificity and accuracy rate. Test of statistical
      significance was with Yates correlation at 95% confidence limit. RESULTS: The
      prevalence of asymptomatic malaria parasitaemia was higher using intradermal
      smear (35.3% vs 33.3%) though this was not statistically significant. Intradermal
      smear had a sensitivity of 40% and specificity of 67%. The positive predictive
      value was 37.8% with accuracy rate of 58%. 41% of participants preferred the
      technique of collection of intradermal blood. CONCLUSION: Intradermal smear
      appears to have no usefulness in the detection of asymptomatic malaria
      parasitaemia in pregnancy. However, we recommend more studies on its value in
      pregnancy, especially amongst symptomatic pregnant women.

PMID- 19767904
TI  - Aetiology of bacteraemia among adult AIDS patients attending Lagos University
      Teaching Hospital (LUTH), Lagos, Nigeria.
AB  - BACKGROUND: Bacteraemia is a relatively common event in HIV-infected patients,
      especially in late infection. Studies in Africa have shown that more than 23% of
      AIDS patients have bacteraemia but there is paucity of data from Nigeria.
      METHODS: Blood samples from 67 consecutive patients with AIDS attending the Lagos
      University Teaching Hospital between April and August 2000 were cultured.
      Temperature, ESR, Full blood count, and where possible CD4 counts were obtained.
      Socio-demographic details were also recorded. Thirty apparently healthy people
      were randomly selected from a low-risk population to act as non-AIDS controls.
      The Oxoid Signal Blood Culture System was used to investigate bacteraemia.
      Antibiotic sensitivity tests were carried out on all isolates. RESULTS: Twenty
      two (33%) of the 67 AIDS patients were culture positive. Non-typhoidal Salmonella
      spp (45.5%), coagulase-negative staphylococci (22.7%) and Staphylococcus aureus
      (18.2%) were most commonly isolated. One isolate each of Klebsiella pneumoniae,
      Pseudomonas aeruginosa and Bacillus spp were identified. All bacteraemic patients
      had temperatures above 38 degrees C and white blood cell counts ranged between
      2,700-13,500/mm(3). There was a high rate of antibiotic resistance particularly
      to chloramphenicol, tetracyclines, cotrimoxazole and beta-lactam antibiotics.
      However, most isolates were still susceptible to gentamicin and the
      fluoroquinolones. There was no significant difference in the socio-demographics
      of the bacteraemic AIDS and non-bacteraemic AIDS patients. CONCLUSION: Salmonella
      spp. were the most common aetiological agent of bacteraemia among AIDS patients
      seen at the Lagos University Teaching Hospital (LUTH), Nigeria. A high
      temperature was a pointer to the presence of bactaeraemia while total white blood
      cell counts were not useful. It is recommended that blood culture should be done
      for AIDS patients with elevated temperature irrespective of the total white blood
      cell count.

PMID- 19767905
TI  - Knowledge and self-perception of breath odour amongst house officers at the
      University College Hospital, Ibadan, Nigeria.
AB  - OBJECTIVE: This study assessed the knowledge and perception of house officers on
      halitosis in the University College Hospital, Ibadan. PATIENTS AND METHODS:
      Questionnaires including items relating to knowledge of halitosis, awareness and
      timing of bad breath, oral hygiene habits and opinions on other issues related to
      bad breath were administered to the subjects. RESULTS: Only seventeen (15.5%) of
      the 110 respondents knew that halitosis refers to malodour originating from the
      oral and nasal cavities while five (5%) were of the opinion that halitosis is
      only a cosmetic problem. Furthermore, thirty nine (35.5%) preferred not being
      told by a friend or colleague if their breath smells badly. CONCLUSION: The
      knowledge and perception of the newly qualified doctors to halitosis in this
      study is unsatisfactory. Therefore, concerted efforts should be made to improve
      them. This could be achieved by more emphasis on this subject during their
      undergraduate training.

PMID- 19767906
TI  - Ultrasonic evaluation of orbito-ocular trauma in Benin-City, Nigeria.
AB  - AIMS AND OBJECTIVES: To find out the causes, time of presentation for ultrasound
      scan, pattern of eye injuries and orbital ultrasound findings in patients with
      orbito-ocular trauma. MATERIALS AND METHODS: Retrospective study of request
      cards, case notes and ultrasound reports of 67 patients who had trauma to the eye
      and were assessed with ultrasonography over a 3-year period (between 20th January
      2000 and 19th January 2003) was done. The collected data included age, sex,
      presenting complaint, past medical history, duration of the injury before
      presentation to ultrasonographic study and ultrasound findings. RESULT: Sixty
      seven patients were seen consisting of 54 males (83.58%) and 11 females (16.42%)
      with male to female ratio of 5:1. Age range was 4 to 91 years with mean age of
      30.8 years. 44 patients (65. 67%) had blunt trauma while 23 patients (34.32%) had
      penetrating trauma. The causes of the ocular trauma include road traffic
      accidents 32 (47.76%), assaults 16 (23.88%), gunshot injuries 10 (14. 93%),
      sports injuries 5 (7.46%), and falls from heights 4 (5.92%) patients. 42 patients
      (53.73%), especially those with severe injuries presented late for
      ultrasonography. Those who made early presentation were cases of assault because
      of police involvement. Forty-five patients (67.16%) had structurally identifiable
      pathology in one or both eyes. Retinal detachment 18 (26.87%), vitreous
      haemorrhage 17 (25.37%), traumatic cataract 13 (19.40), ruptured globe 6 (8.96%)
      and posterior dislocation of the lens 6 (8.96) were the commonest abnormal
      sonographic findings. In 22 patients (32.84%) both eyes were normal. CONCLUSION:
      Ultrasound scan is a useful imaging modality for examination of the globe in
      patients with ocular trauma. Road traffic accident is the commonest cause of
      traumatic ocular injury affecting the globe. Retinal detachment and vitreous
      haemorrhage are the most frequent injuries to the globe diagnosed by ultrasound
      scan. Measures to reduce road traffic accidents will have far reaching positive
      effect in preventing blindness resulting from orbito-ocular trauma in Nigeria.

PMID- 19767907
TI  - Awareness and practice of vasectomy among married male health workers at the
      University College Hospital, Ibadan, Nigeria.
AB  - OBJECTIVE: To determine the awareness and practice of vasectomy among male health
      workers at University College Hospital, Ibadan and the influence of socio
      demographic factors. METHOD: This is a descriptive cross-sectional study in which
      structured self-administered questionnaires were used to interview married male
      health workers at the University College Hospital, Ibadan between May and July
      2006. RESULTS: Two hundred and fifty responses were analysed. The mean age was
      36.7 (+/- 5.4) years. Two hundred and thirty nine (95.6%) respondents were
      married, 10 (4.0%) were separated while one (0.4%) was divorced. One hundred and
      fifty-one (60.4%) respondents were medical doctors while 34 (13.6%) were
      laboratory scientists. Fourteen (5.6%) respondents were pharmacists while 9
      (3.6%) and 23 (9.2%) of the respondents were records officers and nurses
      respectively. Nineteen (7.6%) respondents belonged to other professions. Two
      hundred and twenty five respondents (90%) knew about vasectomy while twenty five
      respondents (10%) were not aware of it. One hundred and forty-five (58.0%) of the
      respondents were unwilling to accept sterilisation as a contraceptive procedure
      while 48 (19.2%) were willing to accept it and the remaining respondents 57
      (22.8%) were uncertain. The cadre of medical profession and being previously
      aware of vasectomy were statistically significant with the willingness to accept
      vasectomy (chi(2) = 20.943, p= 0.021 and chi(2) = 10.666, p = 0.005
      respectively). However none of the respondents had ever had vasectomy done.
      CONCLUSION: Some health workers are not aware of vasectomy or have some
      misconceptions about it. Family planning and contraception should be inculcated
      into the curricula of schools producing health workers such as laboratory
      scientists, radiographers etc. This will go a long way in improving their
      knowledge and attitude to vasectomy.

PMID- 19767908
TI  - Knowledge and practice of food hygiene and safety among food handlers in fast
      food restaurants in Benin City, Edo State.
AB  - OBJECTIVE: To assess the knowledge and practice of food hygiene and safety among
      food handlers in fast food restaurants in Benin City, Edo State. METHODOLOGY: A
      descriptive cross-sectional study was carried out among 350 respondents who were
      selected by means of a systematic sampling method and interviewed using a semi
      structured researcher-administered questionnaire. An observational checklist was
      thereafter used to inspect their personal hygiene status. RESULTS: The mean age
      of the food handlers was 26.4 +/- 6.1 years. Two hundred and twenty eight (65.1%)
      were females while 34.9% were males. A majority (98%) of the respondents had
      formal education. There was good knowledge and practice of food hygiene and
      safety among the respondents. Knowledge was significantly influenced by previous
      training in food hygiene and safety (p = 0.002). Food handlers who had worked for
      longer years in the fast food restaurants had better practice of food hygiene and
      safety (p = 0.036). The level of education of respondents did not significantly
      influenced their practice of food hygiene and safety (p = 0.084). Although, 299
      (85.4%) food handlers were generally clean, skin lesions was seen in 4 (7.3%) of
      them. CONCLUSION: This study showed good knowledge and practice of food hygiene
      and safety by food handlers in the fast food restaurants in Benin City, but there
      is need for improvement through training and retraining of food handlers by the
      management of the restaurants and the local government authorities.

PMID- 19767909
TI  - Outcome of trans-anal posterior anorectal myectomy for the ultrashort segment
      Hirschsprung's disease--Benin City experience in five years.
AB  - OBJECTIVE: The conventional treatment of Hirschsprung's disease involves
      colostomy creation, excision of aganglionic segment, pull through using normally
      ganglionated proximal bowel segment and colostomy closure. The ultrashort segment
      variety is treated with posterior anorectal myectomy which requires no prior
      colostomy creation. This study sought to evaluate the benefits and outcomes of
      the procedure in a tertiary hospital in Nigeria. PATIENTS AND METHODS: All
      children diagnosed with ultrashort segment Hirschsprung's disease between January
      2003 and December 2007 at the University of Benin Teaching Hospital, Benin City,
      were prospectively studied. RESULTS: Of 64 children managed with Hirschsprung's
      disease in five years, 11 (17.2%) were diagnosed with ultrashort segment variety
      and had posterior anorectal myectomy without prior colostomy. They comprised 7
      males and 4 females with male/female ratio 1.8:1 and were aged between 1 month
      and 9 years (mean 1.5 +/- 0.8 years). The procedure was well tolerated and gave
      satisfactory results in all the patients as no wound infection or any life
      threatening morbidity and mortality was recorded. Postoperative pain which
      responded to paracetamol in the majority of children was statistically
      significant in older compared to younger patients (P<0.0001). Oral feeds were
      commenced and tolerated earlier, length of hospitalisation was shorter and no
      incontinence was recorded unlike the conventional treatment. Also, postoperative
      nursing care was easier and the single procedure resulted in availability of
      theatre space for other paediatric operations. All the children did well on 9
      months to 4 years follow-up. CONCLUSION: The procedure was found to be beneficial
      and effective for ultrashort segment Hirschsprung's disease, and should be
      employed in this subregion.

PMID- 19767910
TI  - Stimulant use among secondary school students in Osogbo, Nigeria.
AB  - OBJECTIVES: The objectives of this study were to determine the prevalence and
      pattern of stimulant use and its association with 'brain fag syndrome' among
      secondary school students in Osogbo, Osun State. The study also aimed to
      determine the association of socio-demographic variables (of the students and
      their parents) with stimulant use. MATERIALS AND METHODS: A questionnaire
      consisting of sociodemographic variables, the stimulant use section of the WHO
      Student Drug Use Questionnaire and the Brain Fag Syndrome Scale (BFSS) was
      administered on randomly selected students of the two Local Government Areas of
      Osogbo. The prevalence rates of stimulant use were calculated and the association
      of stimulant use with Brain Fag Syndrome (BFS) and socio-demographic variables
      was determined. RESULTS: The 30-day prevalence rate of stimulant use was 20.3%.
      Users engaged more in the use of common and cheap stimulants (coffee and kola
      nut). Majority of users started at age 13 years or below. There was a very high
      relationship between stimulant use and the symptoms of the BFS (p<0.001).
      Stimulant use was associated with lower age group, poor school attendance,
      polygamous background, low education of mother, high education of father and the
      description of mother as being too permissive. CONCLUSION: The findings suggest
      the need to increase the awareness of the dangers of stimulant use among
      students. Control programmes are urgently needed to prevent student wastage.

PMID- 19767911
TI  - Acquired male urethral diverticulum: case reports.
AB  - Urethral diverticulum is a localised out pouching or fusiform dilatation of the
      urethra. It is an uncommon clinical entity affecting both males and females.
      Although, the diagnosis could be straightforward in the males, it may present as
      a diagnostic puzzle in the female because it often presents with non-specific
      symptomatology and diagnosis may not be easily made with common investigation
      techniques. Two cases of urethral diverticulum are presented to highlight the
      aetiopathogenesis of urethral diverticulum.

PMID- 19767912
TI  - Pleomorphic adenoma of the lateral nasal wall--a case report.
AB  - AIM/BACKGROUND: We report a rare case of pleomorphic adenoma arising from the
      lateral nasal wall. PATIENT AND METHOD: A 23 year old woman presented with a 9
      month history of right sided nasal mass with progressive nasal obstruction. A CT
      Scan of the paranasal sinuses was carried out and the mass was excised
      intranasally. RESULTS: A CT-Scan of the nose and paranasal sinuses showed a soft
      tissue mass in the right nasal vestibule measuring 2.33 x 3.04 cm in its widest
      dimension. There was associated expansion of the cavity with displacement of the
      nasal septum and thinning of the medial wall of the right maxillary antrum
      adjacent to it. The microscopic finding showed a lobular duct-like structure
      within a loose chondromyxoid stroma, which are histological characteristics of
      pleomorphic adenoma. CONCLUSIONS: Her post-operative clinic visits were
      uneventful, and she is currently disease-free; nine months after surgery. The
      diagnosis, clinical behaviour and treatment of pleomorphic adenoma of the lateral
      nasal wall are discussed from a review of the literature.

PMID- 19767913
TI  - Optical encoder based on a nondiffractive beam III.
AB  - In two preceding works (Appl. Opt.47, 2201-2206, 2008; Appl. Opt.48, 414-424,
      2009) we introduced the design of an optical encoder based on a nondiffractive
      beam and studied the dependence of its performance on its parameters (e.g.,
      grating pitch, photodetector size). In those works we proposed different
      optimization criteria and concluded that the proposed design provides an output
      sinusoidal signal with high contrast and very low harmonic distortion, while
      having remarkable tolerance to variations in its parameters and to mechanical
      perturbations. In this work we (1) study how to improve the system performance by
      means of selecting appropriate photodetector geometry, (2) study the system
      performance for different nondiffractive beam geometries, and (3) quantify the
      output signal tolerance to vertical and lateral misalignment between the centers
      of the nondiffractive beam and the photodetector. As a consequence, we obtain new
      sets of optimal parameters that significantly improve the system performance and
      enhance its tolerance to mechanical perturbations and fabrication errors.

PMID- 19767914
TI  - Angle resolved Mueller polarimetry with a high numerical aperture and
      characterization of transparent biaxial samples.
AB  - We present a polarimetric instrument suitable for the simultaneous measurement of
      angle resolved normalized Mueller matrices for polar angles ranging from 0
      degrees to 60 degrees and all azimuths. The polarimetric modulation and analysis
      are performed by means of an optimized polarization state generator and analyzer
      based on nematic liquid crystals. A high numerical aperture (0.95) microscope
      objective is used in double pass to illuminate the sample, with its rear focal
      plane imaged on a low noise CCD. This polarimeter can be used either in
      reflection, with the sample set in the objective front focal plane, or in
      transmission, for thin transparent samples. This latter configuration, which
      involves an additional spherical mirror with its center of curvature at the
      objective front focus, is described in detail. This instrument was used to
      accurately determine the directions of the optic axes and the angular dependence
      of the retardation of a biaxial polyethylene terephthalate (PET) plastic
      substrate in spite of the strong depolarization essentially due to the source 10
      nm spectral width or the limitation in angular resolution due to the pixels
      distribution of the CCD combined with the sample large retardation.

PMID- 19767915
TI  - Color filter based on a two-dimensional submicrometer metal grating.
AB  - A color filter incorporating a two-dimensional (2D) submicrometer metal grating
      is proposed. The device is designed by utilizing rigorous coupled-wave analysis
      (RCWA) and consists of four parts: a polymethyl methacrylate (PMMA) substrate, a
      dielectric film of high refractive index, a submicrometer grating, and a
      dielectric overlay of low refractive index. Its performance is enhanced
      effectively by applying a dielectric film of high refractive index. With a
      dielectric film height of 30 nm, a grating depth of 70 nm, and an overlay height
      of zero, three different devices are designed with the following structural
      parameters: a period of 420 nm for the red, a period of 350 nm for the green, and
      a period of 260 nm for the blue. For the red filter, the center wavelength is 645
      nm and the peak transmission is 72%; for the green one, the center wavelength is
      546 nm and the peak transmission is 75%; and for the blue one, the center
      wavelength is 455 nm and the peak transmission is 71%. The calculated result
      shows that its peak transmission efficiency increased more than 14% compared to
      the previous color filters incorporating a grating.

PMID- 19767916
TI  - Plasmonics enhancement of a luminescent or Raman-active layer in a multilayered
      metallic nanoshell.
AB  - Expressions for the enhancement of the far-field scattering cross section of a
      luminescent or Raman-active compound contained within a multilayered nanosphere
      are derived, where the active compound resides between an outer metallic shell
      and a metallic core. The quasi-static approximation is assumed for silver and
      gold particles using a Lorentz-Drude model of the dielectric function. An attempt
      has also been made to account for the effect of electron scattering from the
      boundaries of the shell on the enhancement calculation.

PMID- 19767917
TI  - Small-hole waveguides in silicon photonic crystal slabs: efficient use of the
      complete photonic bandgap.
AB  - We investigate photonic crystal waveguides that are formed by holes of reduced
      diameter within a hexagonal lattice of cylindrical airholes in thin freestanding
      silicon slabs. The waveguides operate in both an even-symmetry bandgap and a
      partial gap of odd-symmetry modes that form a complete two-dimensional bandgap
      under the light line. The operating frequency is tuned by the small-hole diameter
      to fit within the range of both bandgaps and to match a free-space wavelength of
      1550 nm. Their narrow bandwidth and low group velocity of light propagation
      renders the waveguides useful as filters or sensing elements. Because of the
      strong dependence of the waveguide mode characteristics on structural changes,
      the highest-precision lithographic fabrication techniques must be applied.

PMID- 19767918
TI  - Optimization of output coupling ratio on the performance of a ring-cavity
      Brillouin-erbium fiber laser.
AB  - The operation of a single-wavelength Brillouin-erbium fiber laser (BEFL) system
      with a Brillouin pump preamplified technique for different output coupling ratios
      in a ring cavity is experimentally demonstrated. The characteristics of Brillouin
      Stokes power and tunability were investigated in this research. The efficiency of
      the BEFL operation was obtained at an optimum output coupling ratio of 95%. By
      fixing the Brillouin pump wavelength at 1550 nm while its power was set at 1.6 mW
      and the 1480 pump power was set to its maximum value of 135 mW, the Brillioun
      Stokes power was found to be 28.7 mW. The Stokes signal can be tuned within a
      range of 60 nm from 1520 to 1580 nm without appearances of the self-lasing cavity
      modes in the laser system.

PMID- 19767919
TI  - Enhanced sensitivity for the detection of trace gases using multiple line
      integrated absorption spectroscopy.
AB  - We describe a technique that enhances the sensitivity of a spectrometer for trace
      gas detection employing an external cavity continuously tunable CW quantum
      cascade laser and integrating the absorption spectra across multiple lines of the
      species. We demonstrate the power of this method by continuously recording the
      absorption spectra of NO2 across the R branch from 1628.8 to 1634.5 cm(-1). By
      integrating the resulting spectra, the detection sensitivity of NO2 is improved
      by a factor of 15 compared to the sensitivity achieved using single line laser
      absorption spectroscopy with the same apparatus. This procedure offers much
      shorter data acquisition times for the real-time monitoring of trace gas species
      compared to adding repeated scans of the spectra to improve the signal-to-noise
      ratio.

PMID- 19767921
TI  - Design considerations for short-wavelength operation of 790-nm-pumped Tm-doped
      fibers.
AB  - Tm-doped 790-nm-pumped silica fiber lasers are excellent candidates for producing
      emission at <1.95 microm, but achieving efficient operation at these wavelengths
      requires careful attention to fiber design because of the characteristic three
      level reabsorption effects. We present a discussion of methods for mitigation of
      these effects and two high-efficiency systems that are capable of producing up to
      70 W at <1.92 microm.

PMID- 19767920
TI  - Self-switching of solitons in an AlGaAs nanowire coupler.
AB  - We propose the design of an AlGaAs-nanowire-based coupler. We demonstrate that it
      can be used as a useful soliton switching device at the telecommunication
      wavelength of 1550 nm. Our analysis shows that nonlinear loss due to two-photon
      and three-photon absorption has almost no effect on the transmission
      characteristics of the coupler. The linear loss and the self-steepening effect
      can be made insignificant with a judicious choice of the initial pulse width and
      operating wavelength.

PMID- 19767922
TI  - High fidelity sky coverage analysis via time domain adaptive optics simulations.
AB  - We describe a high fidelity simulation method for estimating the sky coverage of
      multiconjugate adaptive optics systems; this method is based upon the split
      tomography control architecture, and employs an AO simulation postprocessing
      technique to evaluate system performance with hundreds of randomly generated
      natural guide star (NGS) asterisms. A novel technique to model the impact of
      quadratic wavefront aberrations upon the NGS point spread functions is described;
      this is used to model the variations in system performance with different
      asterisms, and is crucial for obtaining accurate results with the postprocessing
      technique. Several design and algorithm improvements help to reduce the residual
      wavefront error in the tip/tilt and plate scale modes that are controlled using
      the NGS asterism. These improvements include choosing the right wavefront sensor
      (WFS) pixel size, optimal pixel weights, and type II control of the plate scale
      modes.

PMID- 19767923
TI  - Microvalve thickness and topography measurements in microfluidic devices by white
      light confocal microscopy.
AB  - A microvalve is a key part in a multilayer microfluidic device to control the
      fluid flow, and its thickness directly determines its performance. In this paper,
      a three-dimensional measurement technology using a white-light confocal
      microscope is developed for measuring both the topography and thickness of
      microvalves. The impact of system parameters and sample parameters on measurement
      accuracy is discussed in detail, particularly for measurement with a dry
      objective. With this technique, the microvalve thicknesses before and after
      bonding were characterized with submicrometer measurement sensitivity and about 1
      microm measurement accuracy.

PMID- 19767924
TI  - Extinction efficiencies for metallic fibers in the infrared.
AB  - Mass density normalized extinction has been both measured and computed throughout
      the infrared for distribution of well-separated synthesized silver fibers. The
      computational basis is a code originally generated for use with Drudian thin
      fibers at millimeter wavelengths and modified for application at wavelengths that
      include molecular and structural (crystalline) resonances as well as thicker
      fibers. The computation involved convolution of fiber responses over
      distributions for both fiber lengths and diameters. Agreement between the
      measured and the computed results was found to be close.

PMID- 19767925
TI  - Tri-arm multipinhole interferometer for wavefront measurement and diffractive
      imaging.
AB  - We propose a tri-arm (or Y-shaped) multipinhole (MP) interferometer for wavefront
      measurement based on a specially designed tri-arm MP plate. We demonstrate that
      the complex amplitude of a wavefront sampled by the tri-arm MP plate inserted
      between the object and the detector plane can be extracted directly from the
      Fourier transform of a far-field diffraction intensity pattern without the need
      for any iterative algorithm. A form of coherent diffractive imaging based on a
      rotatable tri-arm MP plate is also demonstrated, which provides a feasible
      approach for lensless diffractive imaging in real time.

PMID- 19767926
TI  - High-efficiency diffractive beam splitters surface-structured on submicrometer
      scale using deep-UV interference lithography.
AB  - We report highly efficient diffractive beam splitters intended for high-power
      laser applications. Submicron relief structures that work as an antireflective
      layer are formed on the surfaces of a splitter to improve its transmitted
      efficiency. Surface structuring is performed using deep-UV interference
      lithography and reactive ion etching. As immersed in an index-matching liquid,
      the resist layer coated on diffractive surfaces is exposed to the interference
      fringes that are set intersecting the grooves on the surfaces. Rigorously
      designed structures with a period of 140 nm and a depth of 55 nm are lithographed
      onto fused-silica splitters. Splitting efficiencies at 266 nm are increased by 8%
      to compare favorably with a theoretical value, while Fresnel reflections are
      considerably reduced.

PMID- 19767927
TI  - Measurement of low-derivative surface lenses by two-laser holography with
      Bi12TiO20 crystals.
AB  - Refractive and profilometric analyses of lenses with large radii of curvature
      and/or large focal distance were performed through photorefractive holography
      using a Bi12TiO20 crystal as the recording medium and two red diode lasers as
      light sources. Both lasers were properly aligned and tuned in order to provide
      submillimetric synthetic wavelengths providing real-time interferograms in a two
      color holography experiment. The resulting contour interferogram describes the
      form of the wavefront after the beam traveled back and forth through the lens.
      The fringe quantitative evaluation was carried out through the four-stepping
      technique, and the resulting phase map and the branch-cut method were employed
      for phase unwrapping. Exact ray tracing calculation was performed in order to
      establish a relation between the output wavefront geometry and the lens
      parameters such as radii of curvature, thickness, and refractive index. By
      quantitatively comparing the theoretically calculated wavefront geometry with the
      experimental results, errors below 1% for both refractive index and focal length
      were obtained.

PMID- 19767928
TI  - Broadband IR polarizing beam splitter using a subwavelength-structured one
      dimensional photonic-crystal layer embedded in a high-index prism.
AB  - An iterative procedure for the design of a polarizing beam splitter (PBS) that
      uses a form-birefringent, subwavelength-structured, one-dimensional photonic
      crystal layer (SWS 1-D PCL) embedded in a high-index cubical prism is presented.
      The PBS is based on index matching and total transmission for the p polarization
      and total internal reflection for the s polarization at the prism-PCL interface
      at 45 degrees angle of incidence. A high extinction ratio in reflection (>50 dB)
      over the 4-12 microm IR spectral range is achieved using a SWS 1-D PCL of ZnTe
      embedded in a ZnS cube within an external field of view of +/-6.6 degrees and in
      the presence of grating filling factor errors of up to +/-10%. Comparable
      results, but with wider field of view, are also obtained with a Ge PCL embedded
      in a Si prism.

PMID- 19767929
TI  - Temperature feedback control for long-term carrier-envelope phase locking.
AB  - We report a double feedback loop for the improvement of the carrier-envelope
      phase stabilization of a chirped mirror based femtosecond laser oscillator. By
      combining the control of the Ti:sapphire crystal temperature and the modulation
      of the pump power, the carrier envelope offset frequency, fCEO, was locked for
      close to 20 h, which is much longer than the typical phase stabilization time
      with only pump power modulation.

PMID- 19767930
TI  - Gain dispersion for dissipative soliton generation in all-normal-dispersion fiber
      lasers.
AB  - Properties of dissipative solitons generated in all-normal-dispersion fiber
      lasers through the gain dispersion effect are numerically studied by using a
      pulse-tracing technique that considers interaction between gain saturation, gain
      dispersion, cavity dispersion, fiber Kerr nonlinearity, and cavity boundary
      conditions. The numerical results qualitatively match with experimental
      observations and show that the finite gain bandwidth, together with the pump
      power, determines the properties of the generated dissipative solitons, which
      further dictates the performance of the pulse compression.

PMID- 19767931
TI  - Multiple frequency resolution using stressed liquid crystal as a Fourier
      transform spectrometer.
AB  - Stressed liquid crystals are tested with two-wavelength sources and varying
      intensity inputs in order to further examine their functionality as phase
      modulating elements in Fourier transform spectroscopy.

PMID- 19767932
TI  - Influence of molecular scattering models on aerosol optical properties measured
      by high spectral resolution lidar.
AB  - The influence of molecular scattering models on aerosol optical properties
      measured by high spectral resolution lidar (HSRL) is experimentally investigated
      and theoretically evaluated. The measurements analyzed in this study were made
      during three field campaigns by the German Aerospace Center airborne HSRL. The
      influence of the respective theoretical model on spaceborne HSRL retrievals is
      also estimated. Generally, the influence on aerosol extinction coefficient can be
      neglected for both airborne and spaceborne HSRLs. However, the influence on
      aerosol backscatter coefficient depends on aerosol concentration and is larger
      than 3% (6%) at ground level for airborne (spaceborne) HSRLs, which is
      considerable for the spaceborne HSRL, especially when the aerosol concentration
      is low. A comparison of the HSRL measurements and coordinated ground-based
      sunphotometer measurements shows that the influence of the model is observable
      and comparable to the measurement error of the lidar system.

PMID- 19767933
TI  - Using quantum dots to tag subsurface damage in lapped and polished glass samples.
AB  - Grinding, lapping, and polishing are finishing processes used to achieve critical
      surface parameters in a variety of precision optical and electronic components.
      As these processes remove material from the surface through mechanical and
      chemical interactions, they may induce a damaged layer of cracks, voids, and
      stressed material below the surface. This subsurface damage (SSD) can degrade the
      performance of a final product by creating optical aberrations due to
      diffraction, premature failure in oscillating components, and a reduction in the
      laser induced damage threshold of high energy optics. As these defects lie
      beneath the surface, they are difficult to detect, and while many methods are
      available to detect SSD, they can have notable limitations regarding sample size
      and type, preparation time, or can be destructive in nature. The authors tested a
      nondestructive method for assessing SSD that consisted of tagging the abrasive
      slurries used in lapping and polishing with quantum dots (nano-sized fluorescent
      particles). Subsequent detection of fluorescence on the processed surface is
      hypothesized to indicate SSD. Quantum dots that were introduced to glass surfaces
      during the lapping process were retained through subsequent polishing and
      cleaning processes. The quantum dots were successfully imaged by both wide field
      and confocal fluorescence microscopy techniques. The detected fluorescence
      highlighted features that were not observable with optical or interferometric
      microscopy. Atomic force microscopy and additional confocal microscope analysis
      indicate that the dots are firmly embedded in the surface but do not appear to
      travel deep into fractures beneath the surface. Etching of the samples exhibiting
      fluorescence confirmed that SSD existed. SSD-free samples exposed to quantum dots
      did not retain the dots in their surfaces, even when polished in the presence of
      quantum dots.

PMID- 19767934
TI  - Optical waveguide grating couplers: 2nd-order and 4th-order finite-difference
      time-domain analysis.
AB  - Output optical waveguide grating couplers are rigorously analyzed using the 2
      order and the 4-order finite-difference time-domain (FDTD) method in conjunction
      with the total field/scattered field (TF-SF) approach and special averaging and
      regularization techniques for the mitigation of permittivity discontinuities.
      Volume-holographic and surface-relief grating couplers are analyzed for both TE
      and TM polarizations. The 2- and 4-order FDTD results are compared in terms of
      computational efficiency and accuracy. In addition, the FDTD results are compared
      to the approximate ones obtained by the rigorous coupled-wave analysis in
      conjunction with the leaky modes.

PMID- 19767935
TI  - Polarization properties of vertical-cavity surface-emitting lasers subject to
      feedback with variably rotated polarization angle.
AB  - Influences of variable-angle polarization-rotated optical feedback on
      polarization properties of vertical-cavity surface-emitting lasers (VCSELs) are
      investigated numerically. For the so-called case A (x polarization) feedback,
      only the x mode is selected to pass through the feedback loop. As the
      polarization angle is varied from 0 degrees to 90 degrees, the dominant
      polarization mode switching can be observed even for fixed feedback strength and
      bias current. For the so-called case B (xy polarization) feedback, the total
      outputs of the VCSEL pass through the feedback loop. The polarization property is
      much different from case A. The dominant polarization mode switching occurs not
      in the entire range of polarization angles, however, but in the so-called
      critical angle, from where the intensities of both polarization modes become
      comparable to each other and keep around constant values, and can be observed. In
      addition, the complementary properties of intensities between the two
      polarization modes for both cases are evaluated quantitatively in terms of the
      defined normalized intensity.

PMID- 19767936
TI  - Plane wave coupling into single-mode fiber in the presence of random angular
      jitter.
AB  - Efficient coupling of coherent plane waves into single-mode fibers is a key
      technology for free-space optical communication at 1550 nm. Here we deal with the
      influence of random angular jitter on a plane wave to single-mode fiber coupling.
      The expression of mean-coupling efficiency in the presence of random jitter is
      handled in the pupil plane. First, an analytical expression of the mean-coupling
      efficiency is derived for the zero bias error case. Then the bias error was taken
      into account. By minimizing the coupling efficiency penalty, the optimum value of
      design parameter beta of fiber-coupled optical systems in the presence of random
      jitter is obtained. The results obtained here will be useful in facilitating
      parametric estimation and optimization of fiber-coupled optical systems.

PMID- 19767937
TI  - Hardware accelerated optical alignment of lasers using beam-specific matched
      filters.
AB  - Accurate automated alignment of laser beams in the National Ignition Facility
      (NIF) is essential for achieving extreme temperature and pressure required for
      inertial confinement fusion. The alignment achieved by the integrated control
      systems relies on algorithms processing video images to determine the position of
      the laser beam images in real time. Alignment images that exhibit wide variations
      in beam quality require a matched-filter algorithm for position detection. One
      challenge in designing a matched-filter-based algorithm is to construct a filter
      template that is resilient to variations in imaging conditions while guaranteeing
      accurate position determination. A second challenge is to process images for
      thousands of templates in under a second, as may be required in future high
      energy laser systems. This paper describes the development of a new analytical
      template that captures key recurring features present in the beam image to
      accurately estimate the beam position under good image quality conditions.
      Depending on the features present in a particular beam, the analytical template
      allows us to create a highly tailored template containing only those selected
      features. The second objective is achieved by exploiting the parallelism inherent
      in the algorithm to accelerate processing using parallel hardware that provides
      significant performance improvement over conventional processors. In particular,
      a Xilinx Virtex II Pro field programmable gate array (FPGA) hardware
      implementation processing 32 templates provided a speed increase of about 253
      times over an optimized software implementation running on a 2.2 GHz AMD Opteron
      core.

PMID- 19767938
TI  - Characterizing large-area electro-optic crystals toward two-dimensional real-time
      terahertz imaging.
AB  - We have characterized the homogeneity of large-area (>10 mm x 10 mm) CdTe(110)
      and ZnTe(110) crystals using a raster electro-optic scanning method to assess
      their usability in two-dimensional electro-optic terahertz (THz) imaging with
      parallel read out. The spatial variation in the detected THz signal (at 0.2 and
      0.645 THz, respectively) is due to nonuniform residual birefringence and
      scattering. For CdTe, this depends critically on the growth method, and has an
      important contribution from slip planes in the crystals, as is evident in the
      scanned images. For the highest-quality CdTe(110) crystals investigated, the rms
      signal variations are less than 15%, comparable to those for ZnTe(110). For
      electro-optic scanning, we introduce a hybrid measurement system based on a fs
      Nd:glass laser and a continuous-wave electronic THz source.

PMID- 19767939
TI  - Choice of boundary conditions for rectangular dielectric waveguides using
      approximate eigenfunctions separable in x and y.
AB  - In examining approximate eigenfunction solutions of a rectangular dielectric
      waveguide that are separable in x and y, we have found that a particular choice
      of field components of E and H for satisfying the boundary conditions results in
      orthogonal eigenfunctions for the different modes, while other choices do not.

PMID- 19767940
TI  - Tunable holographic Fabry-Perot etalon fabricated from poor-quality glass
      substrates.
AB  - A novel holographic recording method has been demonstrated for fabricating highly
      reflectant mirror coatings on a glass substrate of poor surface quality. Electro
      optically tunable characteristic fringes of a high-finesse Fabry-Perot etalon
      have been observed from a cavity consisting of a thin nematic liquid-crystal
      layer and coated with holographic mirrors. Good agreement has been found between
      measured values and values predicted by coupledwave theory.

PMID- 19767941
TI  - Calculation of higher-order wave-mixing spectra.
AB  - Using diagrammatic perturbation theory, we calculate the higher-order
      susceptibility for the n-wave process, omega(0) = (n/2 - 1)(omega(1) - omega(2))
      + omega(1), in a phase-matched n-wave-mixing geometry. We include the 16 Zeeman
      and hyperfine levels of the sodium ground (3S((1/2))) and excited (3P((1/2)))
      states, finding resonances at subharmonics [+/-(1/2), +/-?, ..., +/-1(n/2 - 1)]
      of the ground-level transition frequencies. The computed spectrum for eight-wave
      mixing is in satisfactory agreement with experiment. In addition, a theoretical
      twelve-wave-mixing spectrum predicts a new higher-order selection rule.

PMID- 19767942
TI  - Mismatched directional couplers.
AB  - Various twin-core couplers composed of mismatched optical fibers are capable of
      complete power transfer over lengths only moderately longer than their matched
      analogs. Examples include tapered and piecewise-continuous mismatched couplers.
      These linear couplers also provide insight into the mechanism of nonlinear
      coupling because nonlinearity induces periodic mismatching between twin cores
      that are axially uniform.

PMID- 19767943
TI  - Mode-holding capability of dual-mode fibers.
AB  - Standard single-mode communication fibers have been characterized with respect to
      their mode-preservation capability in the dual-mode regime. For a 1300-nm single
      mode fiber working at 830 nm, the equivalent h parameter for its LP(01) and
      LP(11) modes is shown to be as good as that for the best polarization-maintaining
      fibers, i.e., better than -20 dB-km.

PMID- 19767944
TI  - Wavelength-division multiplexing and demultiplexing on locally sensitized single
      mode polymer microstructure waveguides.
AB  - A four-channel wavelength-division-(de)multiplexing [WD(D)M] device, operating
      over optical wavelengths of 543.0 to 632.8 nm, has been successfully fabricated
      on newly developed locally sensitized polymer (photo-lime gelatin) microstructure
      waveguides (PMSW's). The WD(D)M device exhibits a cross talk of less than -40 dB
      between adjacent channels and a diffraction efficiency of better than 50%. The
      angular and spectral bandwidths for the device are ~0.2-0.4 degrees and ~4-10 nm,
      respectively. Such sensitivities can significantly increase the WD(D)M channel
      density for optical interconnect architectures. Since the PMSW device can be
      constructed on a variety of substrates, including insulators, semiconductors,
      conductors, and ceramics, the demultiplexing technique that we report is suitable
      for use in a variety of optical-computing, signal-processing, and communication
      applications.

PMID- 19767945
TI  - Integrated-optic laser fabricated by field-assisted ion exchange in neodymium
      doped soda-lime-silicate glass.
AB  - A continuous-wave integrated-optic channel waveguide laser operating at 1.057
      microm has been fabricated in neodymium-doped soda-lime-silicate laser glass. The
      device was end-fire pumped with the 0.528-microm line of an argon-ion laser.
      Threshold for laser action occurs for an absorbed pump power of 31 mW. The slope
      efficiency for the integrated-optic laser is estimated to be 0.5%. Field-assisted
      ion exchange in a eutectic melt of CaNO(3) and KNO(3) was used to form the
      waveguide.

PMID- 19767946
TI  - Two-piece, piezoelectrically tuned, single-mode Nd:YAG ring laser.
AB  - A two-piece, single-mode, piezoelectrically tuned Nd:YAG ring laser has been
      demonstrated at 1338 nm. The laser was derived from a previously demonstrated
      monolithic unidirectional ring laser that has been cut in two to allow the cavity
      to be tuned by varying the gap between the two pieces. More than 1 mW of output
      power was produced when the laser was pumped by a 30-mW, 809-nm GaAlAs
      semiconductor laser. Continuous tuning over the 13.5-GHz longitudinal mode
      spacing with millisecond sweep times was demonstrated.

PMID- 19767947
TI  - Second-harmonic generation and optical stabilization of a diode laser in an
      external ring resonator.
AB  - The second harmonic of the 842-nm output of a GaAlAs diode laser is generated in
      a KNbO(3) crystal in a resonant, external ring cavity. The diode laser is
      optically stabilized to the ring cavity through feedback from the
      counterpropagating fundamental wave, which is weakly excited in the resonator. We
      have produced 6.7 mW of tunable, narrowband radiation at 421 nm and have used
      that light to perform saturation spectroscopy on narrow transitions in rubidium.

PMID- 19767948
TI  - Ti:sapphire laser pumped by a frequency-doubled diode-pumped Nd:YLF laser.
AB  - We report on the operation of a tunable all-solid-state (holosteric) laser system
      consisting of a tunable Ti:sapphire laser pumped by a frequency-doubled diode
      laser-pumped Nd:YLF laser. With a 1-W pump diode, the Nd:YLF laser has been
      frequency-modulation mode locked and Q switched at 1.047 microm. This produces a
      pulse envelope of 75-nsec duration with 45 microJ of energy in 21-psec pulses at
      a 360-MHz repetition rate. This output was frequency doubled in 90 degrees phase
      matched MgO:LiNbO(3) with a 47% energy conversion efficiency. The Ti:sapphire
      cavity was a three-mirror astigmatically compensated arrangement.The threshold
      absorbed pump energy was 3.9 microJ, with an output energy of 1.3 microJ at 10.8
      microJ absorbed pump power.The tuning range was 746-838 nm and was limited by the
      mirror reflectivities.

PMID- 19767949
TI  - Mode locking of a continuous-wave titanium-doped sapphire laser using a linear
      external cavity.
AB  - The mode locking of a Ti:Al(2)O(3) laser with a moving extracavity mirror is
      described. With no active mode-locking element and with no nonlinear element in
      the external cavity, pulses of less than 40 psec have been directly generated
      from a cw laser. A possible mechanism for this novel mode-locking technique is
      discussed.

PMID- 19767950
TI  - Spectral shaping in chirped-pulse amplification.
AB  - The role of spectral shaping in the production of subpicosecond, high-contrast
      pulses by using chirped-pulse amplification in Nd:glass lasers is described.
      Spectral shaping has been used to produce 3.2-TW pulses at 750 fsec with an
      energy contrast of better than 10(3):1. In the absence of shaping, compression of
      the 1053-nm pulses yielded only 1.5 psec and a contrast ratio of approximately
      10:1.

PMID- 19767951
TI  - Detection of 532-nm frequency-doubled Nd:YAG radiation in an active rubidium
      atomic resonance filter.
AB  - We report the detection of frequency-doubled Q-switched Nd:YAG laser radiation at
      532.24 nm by an active rubidium atomic resonance filter. The Rb 5p level was
      populated by using a diode laser operating at 795 nm. The 532-nm laser excited
      atoms to the 10s level; these decay through p levels to the ground state. Signals
      were observed at 420/422 nm and 359 nm, corresponding to fluorescence from states
      6p and 7p. Fluorescence noise was observed only on the 420/422-nm transition; the
      359-nm signal had no detectable noise.

PMID- 19767952
TI  - Frequency pulling of stimulated Raman scattering in microdroplets.
AB  - Spectral features observed in stimulated Raman scattering from 20-microm methanol
      droplets at 1-GW/cm(2) pumping levels appeared locked in wavelength at the center
      of their respective gain profiles. Typically, a feature's wavelength remained
      constant while the droplet size varied by as much as 0.3%. This is attributed to
      frequency-pulling effects caused by the presence of Raman gain. Wavelength shifts
      of up to +/-0.5 nm in the positions of morphologydependent resonances would
      explain the observations and are consistent with calculations.

PMID- 19767953
TI  - Pulsed squeezed-light measurement: a new technique.
AB  - A transient noise measurement scheme is described to observe pulsed squeezing
      generated by means of parametric downconversion of a Q-switched laser. In the
      usual implementation of balanced-homodyne detection, the vacuumstate noise level
      is determined by the average local oscillator power. However, if the local
      oscillator is derived from a pulsed laser, as is the case in our experiments, the
      associated peak power can easily saturate the detectors along with the subsequent
      electronics. To overcome this limitation we have implemented a hybrid frequency
      time-domain measurement scheme in which the vacuum-state noise level is
      determined by the peak, instead of the average, local oscillator power, thus
      avoiding the saturation problem.

PMID- 19767954
TI  - Group-delay measurement using the Fourier transform of an interferometric cross
      correlation generated by white light.
AB  - A new method and apparatus for measuring the group delay in optical components
      and laser cavities are described. Cross-correlational fringes are fully recorded
      with a Michelson interferometer, in one of whose arms the optics to be measured
      are inserted. The path difference of the interferometer is calibrated to
      subwavelength accuracy, and the group delay is calculated from the phase of the
      Fourier transform of the measured fringe. The group delay for the entire visible
      wavelength region is evaluated after a single measurement in approximately 10
      min, using white light.

PMID- 19767955
TI  - Tomographic imaging of micrometer-sized optical and soft-x-ray beams.
AB  - The knife-edge technique for measurements of micrometer-sized beams is extended
      to two-dimensional imaging by tomographic reconstruction of multiangular knife
      edge data. Two-dimensional intensity distributions at optical (633-nm) and soft-x
      ray (13.5-nm) wavelengths at the focal region of a Schwarzschild objective are
      presented. The resolution is limited by the 200-nm step size used in the data
      acquisition.

PMID- 19767956
TI  - Photosensitive optical fibers used as vibration sensors.
AB  - We experimentally demonstrate that high-reflectivity photosensitive gratings
      written in optical fibers can be used to detect vibrations that produce length
      changes of less than 50 nm. This sensitivity to external perturbations can also
      explain the high-frequency components often observed during the growth of these
      gratings.

PMID- 19767957
TI  - Generation of dark solitons under a cw background using waveguide electro-optic
      modulators.
AB  - We propose a novel method for generating dark solitons with a cw background by
      using broadband guided-wave electro-optic modulators. The generated pulse can be
      amplified by stimulated Raman scattering to permit the observation of soliton
      effects in the fiber.

PMID- 19767958
TI  - Theory of elliptical defocusing in anisotropic nonlinear-optical media.
AB  - We have determined the far-field beam profiles of an initially Gaussian laser
      beam that traverses a thin slab of nonlinear-optical material in which the
      spatial distribution of the refractive nonlinearity is anisotropic by an
      expansion in terms of elliptical Gaussian functions. In marked contrast to the
      annular structures observed with isotropic media, it is shown that the
      transmitted beam breaks into two beams in the far field. This nonlinear beam
      splitting behavior has been confirmed experimentally.

PMID- 19767959
TI  - Feedback-enhanced bistability in grating coupling into InSb waveguides.
AB  - We show that the bistability obtained through grating coupling into a waveguide
      with a diffusive nonlinearity is enhanced in the presence of a second
      counterpropagating guided-wave beam. An integrated device in which a nonlinear
      distributed-feedback grating is used to retroreflect the incoupled beam is
      demonstrated.

PMID- 19767960
TI  - Measuring photorefractive trap density without the electro-optic effect.
AB  - Two optical beams can couple in a photorefractive crystal without using the
      electro-optic effect. Beam coupling is due to a spatially modulated absorption
      caused by the rearrangement of trapped charges. We use these gratings to
      determine the effective photorefractive trap density for several barium titanate
      crystals.

PMID- 19767961
TI  - All-optical cascadable NOR gate with gain.
AB  - An ultrafast, all-optical, three-terminal NOR gate based on soliton dragging in
      fibers is demonstrated with a gain of 4.5 and a switching energy of 30 pJ.
      Cascadability is proved with a tandem of two NOR gates that are configured as
      inverters. Time shifts from soliton dragging between two orthogonally polarized
      pulses in a fiber can be used for logic operations in a clocked system. Larger
      than-predicted time shifts are observed because of self- and cross-Raman
      amplification effects.

PMID- 19767962
TI  - Far-field power-distribution measurement in axially symmetrical and
      nonsymmetrical fibers using a variable-width slit.
AB  - A method for the measurement of the far-field power radiation pattern in axially
      symmetrical and nonsymmetrical single-modeoptical fibers is proposed. The method,
      based on monitoring of the power passed through a variablewidth slit in the far
      field, gives the power distribution as an associated Gauss-Laguerre expansion.
      The experimental setup permits the study of the power distribution and mode-field
      diameter dependence on the wavelength. Results for different types of single-mode
      optical fiber, including polarization-maintaining types, are presented.

PMID- 19767963
TI  - Wavelength dependence of the scattering loss in fluoride optical fibers.
AB  - Scattering losses as low as 0.025 dB/km at 2.55 microm have been measured in
      short lengths of fluoride-glass optical fiber.These measurements were made on
      several 5-7-cm lengths of fiber. Measurements were also made at various
      wavelengths to determine the wavelength dependence of the optical loss.

PMID- 19767964
TI  - Nonlinear coupling in a planar waveguide.
AB  - The thermal nonlinear response of a waveguide produced by sputtering a Corning
      7059 glass film over a nonlinear substrate(Corning CS2-61) is studied with a pump
      probe technique in a quasi-cw regime. The coupling efficiency is found to
      beafunction of pump power and chopping frequency. The coupling zone is scanned
      with a probe beam to examine the spatial dependence of the coupling efficiency.

PMID- 19767965
TI  - Negative-branch unstable-resonator copper-vapor laser.
AB  - Copper-vapor lasers (CVL's) with positive-branch unstable resonators have been
      used extensively for reducing output-beam divergence. In contrast, the negative
      branch unstable resonator has not been applied to CVL's. Here we study the
      performance of a negative-branch unstable-resonator CVL with various
      magnifications. A divergence of approximately 3.25 times the diffraction limit
      was obtained.

PMID- 19767966
TI  - Limits imposed by spatial hole burning on the single-mode operation of standing
      wave laser cavities.
AB  - A simple formula is derived that gives the ratio of the maximum single
      longitudinal-mode inversion density to the threshold inversion density for a
      standing-wave laser in terms of the cavity geometry and well-known material
      parameters. This formula can be used as a guideline in the design of single
      frequency lasers.

PMID- 19767967
TI  - Performance of gain-switched Ti:A12O3 unstable-resonator lasers.
AB  - We describe an experimental investigation of Ti:A1(2)O(3) unstable-resonator
      lasers. A near-diffraction-limited output of 430 mJ in a 10-nsec pulse at 10 Hz
      has been obtained, which is to our knowledge the highest peak power from a
      Ti:A1(2)O(3) laser reported. We report results for both standing-wave and
      traveling-wave oscillators, demonstrating line narrowing by means of prism tuning
      and injection seeding.

PMID- 19767968
TI  - Observation of laser oscillation in nitric oxide at 218 nm.
AB  - We have recently proposed a scheme to produce coherent radiation at eight or more
      wavelengths between 158 and 242 nm by optically pumping a high-lying electronic
      level of nitric oxide. We report here the successful operation of this scheme to
      produce laser oscillation at 218 nm. The possibility of using this scheme to
      produce laser oscillation at other wavelengths is discussed.

PMID- 19767969
TI  - Passive Q switching of a diode-pumped Nd:YAG laser with a saturable absorber.
AB  - A diode-pumped Nd:YAG laser is passively Q switched by using F(2)(-) color
      centers in lithium fluoride as a saturable absorber. When cw pumped with a laser
      diode, the laser produces pulses of 20-30-nsec duration at 1064 nm, with an
      energy of as much as 20 microJ and a peak power of more than 1 kW. Data are
      presented on pulse width, energy, and repetition rate as a function of pump
      power. When the laser is operated at high pulse energy levels, a gradual
      bleaching of the saturable absorber is observed.

PMID- 19767970
TI  - Colliding visible picosecond pulses in optical fibers.
AB  - The observation of the nonlinear interaction of two visible picosecond pulses,
      separated by a small time interval, while propagating in an optical fiber is
      reported. It is found that as propagation proceeds, a region of pulse collision
      develops in which intensity oscillations form that are similar to those recently
      observed in optical wave breaking. The frequency of these oscillations increases
      for an increasing time separation between the input pulses and is found to be as
      large as 5 THz. For small time intervals between the input pulses no oscillations
      formed. This observed behavior is found to agree well with numerical integrations
      of the nonlinear Schrodinger equation.

PMID- 19767971
TI  - Femtosecond pulses at 800 nm by passive mode locking of Rhodamine 700.
AB  - We report the passive mode locking of a Rhodamine 700 dye laser in the near
      infrared. Using a short cavity in order to avoid multiple pulses and by adjusting
      the intracavity dispersion, we have produced 50-fsec pulses at 800 nm with HITCI
      as the saturable absorber.

PMID- 19767972
TI  - High-performance single-mode fiber polarization-independent isolators.
AB  - The design and performance of polarization-independent isolators that are
      substantially insensitive to variations of temperature and wavelength are
      presented. Three single-mode fiber isolators have been designed, constructed, and
      tested. The first isolator is a 1.3-microm two-stage isolator that has more than
      40 dB of isolation and less than 2.0 dB of insertion loss over the temperature
      range of 15-70 degrees C. The second isolator is a two-stage dual-wavelength
      isolator with an insertion loss of less than 4 dB and an isolation of better than
      35 dB at 1.3 and 1.52 microm over the temperature range of 15-75 degrees C. The
      third isolator is a three-stage isolator with an insertion loss of less than 2.5
      dB and an isolation of better than 63 dB over the wavelength range 1275-1355 nm.

PMID- 19767973
TI  - Temperature, intensity, and field dependence of the absorption coefficient of
      Bi(12)SiO(20).
AB  - Department of Applied Physics, Stanford University, Stanford, California 94305We
      report the observation of incident intensity and applied-field-induced increases
      in the absorption coefficient of Bi(12)SiO(20) at 514.5 nm. Absorption changes as
      large as 50% have been observed, but 10% is more typical. The main effect is
      thermal shifting of the absorption edge caused by ohmic heating from the
      photocurrent: Deltaalpha(T) = 0.0083 cm(-1) K(-1). In addition, there is a small
      absorption change proportional to the intensity alone that is approximately given
      by Deltaalpha(I) = 0.03 ln(I). We also report a linear decrease in the
      photoconductivity with temperature for T in the range 295-330 K.

PMID- 19767974
TI  - Optically coupled technique for photorefractive surgery of the cornea.
AB  - A novel optically coupled laser probe and method that achieve noninvasive in vivo
      refractive flattening of the cornea of experimental eyes is described. This new
      refractive surgery concept is based on the highly localized photodisruption
      and/or photoablation of tissue within the stromal layer of the cornea without
      other layers' being affected. This is accomplished by a microscope probe that is
      optically index matched to the corneal surface, thereby achieving high numerical
      apertures. The sharp focal volume ensures highly localized energy deposition.
      Preliminary results in rabbit, primate, and human eye-bank eyes indicate
      significant permanent refractive changes with an exceptionally small amount of
      tissue modification.

PMID- 19767975
TI  - Modified P-Q plot of light scattering for large size parameters.
AB  - A new plot for the forward-scattering amplitude in the complex domain is
      proposed. The plot graphs the imaginary part versus the real part with the edge
      effects properly subtracted. Interesting features of the new plot are discussed
      for light scattering by a dielectric sphere.

PMID- 19767976
TI  - Array of grating-fiber couplers.
AB  - Along a single-mode fiber a number M of grating-fiber couplers are fabricated at
      equal spacings L(0). The fiber is coiled so that the couplers lie side by side,
      forming a planar optical antenna array. With varying optical frequency the
      resulting radiation lobes sweep slowly along the meridional direction but fast
      along the orthogonal azimuthal direction. In a spectrometer-type setup with M = 3
      and L(0) = 300 mm a frequency resolution of 230 MHz is demonstrated.

PMID- 19767977
TI  - Soliton self-frequency shift versus Galilean-like symmetry.
AB  - We show that the soliton self-frequency shift (SSFS) law as well as an
      approximate analytical description of the pulse deformation can be obtained on
      the basis of a Galilean-like symmetry of the simplest SSFS model.

PMID- 19767978
TI  - Misalignment sensitivity of beam combining by stimulated Brillouin scattering.
AB  - Stimulated Brillouin scattering beam combining is shown to be extremely sensitive
      to optical misalignments. For the coupling of two overlapping beams, the angular
      misalignment bandwidth is of the order of 1 mrad, which corresponds to a
      separation of +/-0.64 beam spot diameter. This occurs for beam displacements
      normal to the plane defined by the beams' propagation paths.

PMID- 19767980
TI  - Existence of solitary waves in optical fibers owing to the mutual support between
      bright and dark pulses.
AB  - We introduce a new type of solitary wave in a lossless single-mode fiber in which
      a bright solitonlike pulse in the anomalous-dispersion range propagates together
      with a stationary dark pulse in the normal-dispersion range. Such a solitary wave
      can be generated by launching a bright pulse in the anomalous-dispersion range
      together with a long pulse of the same speed in the normal-dispersion range into
      a fiber. The results of numerical simulations show that the dark pulse is not a
      dark soliton. The generation and maintenance of such a solitary wave are
      attributed to the mutual chirping through cross-phase modulation between those
      two waves in the anomalous- and normal-dispersion ranges.

PMID- 19767979
TI  - Observation of spatial optical solitons in a nonlinear glass waveguide.
AB  - We report the observation of spatial optical solitons due to the Kerr
      nonlinearity in a planar glass waveguide and present measurements of the
      nonlinear response obtained by placing a pinhole at the output of the waveguide.
      For input intensities greater than that required for the fundamental soliton, we
      observe breakup of the output owing to the effect of two-photon absorption.

PMID- 19767981
TI  - Soliton switch using birefringent optical fibers.
AB  - The use of solitons is proposed for interferometric switching in birefringent
      optical fibers. Pulse propagation in the fiber is modeled by the coupled
      nonlinear Schrodinger equation, in which the ratio between the self-coupling and
      cross-coupling terms depends on the ellipticity of the fiber eigenmodes. It is
      shown that shadows occur unless the self-coupling and the cross-coupling are
      equal and that these shadows seriously affect the contrast ratio attainable by a
      switch. These two couplings become equal at an ellipticity angle theta
      approximately 35 degrees , and, within a tolerance of theta = +/-5 degrees , a
      contrast ratio of 10 or more can be achieved.

PMID- 19767982
TI  - High-power cadmium photoionization laser pumped by soft x rays from a laser
      produced multispot plasma.
AB  - Soft x rays from as many as nine plasma spots, produced by a 1-J, 8-nsec Nd:YAG
      laser system, have been used to excite Cd atoms by inner-shell photoionization
      and to generate high-power laser radiation in Cd(+) at 442 and 325 nm. With our
      multifoci setup a strong reduction of photoelectron impact and radiation losses
      during the excitation and laser process was possible, resulting in Cd(+) laser
      output energies (peak powers) as high as 1.1 mJ (85 kW) at 442 nm and 140 microJ
      (11 kW) at 325 nm, which are, to our knowledge, the highest achieved to date.

PMID- 19767984
TI  - Efficient, broadly tunable, laser-pumped Tm:YAG and Tm:YSGG cw lasers.
AB  - Broadly tunable cw laser emission is reported in Tm:YAG and Tm:YSGG at room
      temperature with Ti:sapphire laser pumping. The Tm(3+)(3)F(4) ? (3)H(6)
      transition is tuned continuously over the ranges 1.87-2.16 microm in YAG and 1.85
      2.14 microm in YSGG. Smooth tuning results from overlapping transitions between
      phonon-broadened crystal field Stark levels.

PMID- 19767983
TI  - Alignment-stabilized grating-tuned external-cavity semiconductor laser.
AB  - We have demonstrated an alignment-stabilized cavity configuration for a grating
      tuned external-cavity semiconductor laser using a cylinder lens to form a line
      focus on the surface of the grating. The grating in the stabilized cavity has a
      350-fold greater angular misalignment tolerance than in a conventional collimated
      beam cavity, while the same spectral resolution is maintained.

PMID- 19767985
TI  - Decay and interaction of femtosecond optical solitons induced by the Raman self
      scattering effect.
AB  - The influence of the significantly nonstationary Raman contribution to nonlinear
      susceptibility on the dynamics of femtosecond optical solitons interaction and
      decay is theoretically analyzed. The theoretical results are in good quantitative
      agreement with the recent experiments of Mitschke and Mollenauer [Opt. Lett. 11,
      659 (1986); 12, 355 1987)].

PMID- 19767986
TI  - Measurement of group delay with high temporal and spectral resolution.
AB  - We have developed a technique to measure the group-delay time of optical
      components with a temporal resolution of +/-0.1 fsec and a spectral resolution of
      0.1 nm over the spectral region 600-640 nm. The group delay is determined from a
      measurement of the optical path length through the component as a function of
      wavelength with a phase-locked interferometer.

PMID- 19767987
TI  - Intrafiber visible pulse compression by cross-phase modulation in a birefringent
      optical fiber.
AB  - Detailed subpicosecond observations of the time dependence of a propagating cross
      phase-modulated pulse are presented. It is observed that propagation of a weak
      visible pulse in one polarization mode of a birefringent optical fiber, so that
      it is cross-phase modulated by the edge of a strong pulse in the other mode, can
      result in significant compression of the weak pulse, for normal dispersion,
      without external compensation. The compression efficiency is found to be enhanced
      by utilizing the group-velocity mismatch between the two modes to synchronize the
      weak pulse with the broadening edge of the strong pulse. This is the first
      observation, to the author's knowledge, of intrafiber pulse compression for
      normal group-velocity dispersion, and a compressed pulse width of 0.3 psec for a
      2-psec input pulse is observed.

PMID- 19767988
TI  - Low-dispersion, high-gain femtosecond optical pulse amplifier.
AB  - We demonstrate a novel amplifier for femtosecond optical pulses. The output of a
      colliding-pulse mode-locked laser is amplified to 0.3 microJ per pulse at a
      repetition rate of 8 kHz by using 1 W of pump power from a copper-vapor laser.
      Our high-efficiency amplifier focuses the beam for four gain passes through a
      thin dye stream that uses a Z configuration with matched focusing. Because of low
      group-velocity dispersion, the output pulses are only slightly broadened, from 63
      to 73 fsec, and may be used directly to generate a white-light continuum without
      pulse compression after amplification.

PMID- 19767989
TI  - Observation of molecular vibrations in the time domain with incoherent laser
      pulses.
AB  - With the method of self-diffraction of incoherent light, molecular vibrations
      were observed in real time in various dye molecules pumped near the absorption
      edge. In Rhodamine 560, 35-fsec oscillations in the signal were measured, which
      corresponds to a vibrational frequency of 1000 cm(-1). Simultaneously, this
      technique can be used to deduce the ultrafast dephasing times in the molecular
      vibrational quasi-continuum. Dephasing times of 20 and 150 fsec were observed in
      Rhodamine 590 and Rhodamine 560, respectively.

PMID- 19767990
TI  - Self-starting additive-pulse mode-locked diode-pumped Nd:YAG laser.
AB  - A diode-pumped Nd:YAG laser is demonstrated by using self-starting additive-pulse
      mode locking with a nonlinear external cavity. Pulse durations of 1.7 psec are
      generated at an average output power of 25 mW without the need for active
      amplitude or phase modulation. Design and scaling issues for this technology are
      discussed.

PMID- 19767991
TI  - Observations of sodium atoms in a magnetic molasses trap loaded by a continuous
      uncooled source.
AB  - We describe observations of atoms trapped in magnetic molasses made by using a
      simplified apparatus that is loaded by a continuous uncooled source of atoms. We
      also measured the cross section for collisions in which trapped sodium atoms are
      ejected from the trap by thermal sodium atoms and estimate that the cross section
      is 30 times larger than for collisions with other background thermal atoms.

PMID- 19767992
TI  - Enhanced holographic image intensification in BaTiO(3) photoelectrets.
AB  - We report an enhanced holographic image amplification gain of over 24,000 at a
      wavelength of 514.5 nm by using a BaTiO(3) photoelectret. The energy-transfer
      efficiency and amplification factor are found to depend on critical polarization
      conditions of the photoelectret, the beam-mixing geometries, and the intensity
      ratios between the reference and the object beams. The results obtained
      corresponding values reported previously.

PMID- 19767993
TI  - Performance of surface-plasma-wave fiber-optic polarizers.
AB  - Variations in the TM-like polarization transmission characteristics and
      polarization extinction ratio of surface-plasma-wave fiber-optic polarizers owing
      to variations in the depth of polishing and the metal film thickness are
      presented. The two effects have been isolated in carefully designed experiments
      and studied separately.

PMID- 19767994
TI  - Spatial walk-off polarizer utilizing artificial anisotropic dielectrics.
AB  - We propose a new spatial walk-off polarizer that utilizes artificial anisotropic
      dielectrics. The polarizer is composed of two kinds of periodically laminated
      dielectric layer. We calculated the characteristics of the polarizer composed of
      periodically laminated a-Si/SiO(2) layers and found that the split angle between
      the ordinary wave and the extraordinary wave in the polarizer is more than three
      times larger than that in well-known birefringent crystals, e.g., rutile and
      calcite. The polarizer holds promise for the miniaturization of polarization beam
      splitters and polarization-independent isolators.

PMID- 19767996
TI  - Effect of layer thickness variations in a distributed-Bragg-reflector mirror on
      the phase of the reflected light.
AB  - We present an analytical derivation of the phase change of the reflection
      coefficient of a distributed-Bragg-reflector mirror when the thickness of a layer
      in the mirror changes. These phase changes are additive, as has been verified by
      an exact numerical calculation using transmission matrices. Such a phase change
      will affect the lasing wave-length of vertical-cavity surface-emitting lasers and
      the center wavelength of various integrated Bragg devices.

PMID- 19767995
TI  - Continuously tunable smectic A(*) liquid-crystal color filter.
AB  - A new continuously tunable color filter, which uses smectic A(*) liquid-crystal
      half-wave plates, is described and experimentally demonstrated. Multiple-stage
      Lyot filters with broad tunability and high finesse can be constructed with this
      design. The transmission characteristics of a single-stage filter, which is
      continuously tuned over 115 nm of the visible spectrum, are presented.
      Experimental results are compared with computer simulations, and they show
      excellent agreement. The advantages of the smectic A(*) liquid-crystal tunable
      filter over existing filter structures include low switching voltages (+/-30 V),
      rapid tunability (10 MHz), potentially high transmission, wide field of view, and
      large aperture.

PMID- 19767997
TI  - Soft-x-ray projection lithography: printing of 0.2-microm features using a 20:1
      reduction.
AB  - We demonstrate nearly diffraction-limited printing of 0.2-microm features, using
      soft x rays of approximately 36-nm wavelength. An open-stencil transmission mask
      with minimum features of 4 microm was imaged by a twentyfold-reduction
      Schwarzschild-type objective onto silicon wafers coated with various e-beam
      resists. Implications for soft-x-ray projection lithography are discussed.

PMID- 19767998
TI  - Realization of a new concept for visible frequency division: phase locking of
      harmonic and sum frequencies.
AB  - We explore and demonstrate the feasibility of an optical-frequency-to-radio
      frequency division method that is based on visible or near-infrared laser
      oscillators only. Comparing harmonic and sum frequencies, we generate the
      arithmetic average of two visible frequencies. Cascading n stages provides
      difference-frequency division by 2(n). For a demonstration we have phase locked
      the second harmonic and the sum frequency of two independent diode lasers.

PMID- 19767999
TI  - Directional couplers composed of non-Kerr-law material.
AB  - The effects on propagation in directional couplers made of non-Kerr-law material
      are examined. Many unstable modes can exist at one input power level, in contrast
      to only one for Kerr-law material. Special design features are possible by
      tailoring the dependence of the refractive index on intensity.

PMID- 19768000
TI  - Photoinduced absorption in photorefractive barium titanate.
AB  - Spectral and temporal characteristics of the photoinduced absorption in barium
      titanate were measured. Absorption peaks were observed at 450 and 820 nm with 60
      msec decay times and at 775 nm with a 6-sec decay time.

PMID- 19768001
TI  - Hollow sapphire fibers for the delivery of CO(2) laser energy.
AB  - Hollow sapphire tubing has been used to deliver nearly single-mode CO(2) laser
      energy. The hollow single-crystal A1(2)O(3) fiber has an n < 1 cladding at 10.6
      microm. Measured losses at 10.6 microm are as low as 0.49 dB/m, and the minimum
      bend radius of the 580, microm x 380 microm fiber is 14 cm. Bending losses are
      shown to vary as 1/R, and essentially only the HE(11) mode propagates in the bent
      guide.

PMID- 19768002
TI  - Hydrogenated amorphous germanium detectors deposited onto channel waveguides.
AB  - We have fabricated hydrogenated amorphous germanium photodetectors coupled to
      channel waveguides in glass and lithium niobate substrates. We measured a pulse
      response duration of 140 psec (FWHM), which is shorter than that of any
      previously reported photodetectors deposited onto dielectric waveguides. The
      optical gap, which determines the spectral response characteristics, is
      approximately 1.2 eV. We have measured a photoconductive gain of 18 in phosphorus
      doped detectors.

PMID- 19768003
TI  - Evaluation of (4)I(15/2) and (4)I(13/2) Stark-level energies in erbium-doped
      aluminosilicate glass fibers.
AB  - Spectroscopic measurements of fluorescence and absorption in an erbium-doped
      fiber permit the evaluation of the Stark-level energies of the (4)I(15/2) and
      (4)I(13/2) manifolds in Er:glass. The data permit the allocation of the
      individual laser transitions associated with the room-temperature gain spectrum
      of erbium-doped fiber amplifiers operating near lambda = 1.53 microm.

PMID- 19768004
TI  - Derivation and measurement of the reversible temporal lengthening of femtosecond
      optical pulses for the case of a four-prism sequence.
AB  - An expression is derived for the reversible lengthening of optical pulse
      durations from the order of 50 fsec to the order of 500 fsec by a four-prism
      sequence and focusing elements. This temporal lengthening is caused by spatial
      dispersion of the different frequency components transverse to the direction of
      propagation at the symmetry plane of the prism sequence. Experimental
      measurements of the pulse lengthening agree well with calculated values.

PMID- 19768005
TI  - Self-starting additive-pulse mode locking of a Nd:YAG laser.
AB  - We report additive-pulse mode locking of lamp-pumped Nd:YAG lasers at both 1.06
      and 1.32 microm. Under completely self-starting conditions, stable cw mode-locked
      trains of 6-psec pulses have been achieved at an average output power of 2.4 W.

PMID- 19768006
TI  - Iterative generation of holograms on spatial light modulators.
AB  - Iterative learning procedures on a hybrid electro-optic system can be employed to
      generate holograms on inexpensive liquid-crystal-television spatial light
      modulators. The algorithm takes into account random electronic noise in the
      system and compensates for spatial-light-modulator distortions. Experimental
      results are given for the reconstruction of intensity distribution, and computer
      complex amplitude reconstruction.

PMID- 19768007
TI  - Experimental investigation of radiation from the interaction of an electron beam
      and a conducting grating.
AB  - Recent experimental results on the radiation generated from an electron beam
      passing closely over a conducting grating are presented. The most striking
      results are that the output power is 4 orders of magnitude more intense than that
      predicted by the Smith-Purcell explanation and that the output power increases
      exponentially with the beam thickness until it saturates at a thickness of a 1000
      times the grating period. The recent theoretical model of Chang and McDaniel
      [Phys. Rev. Lett. 63, 1066 (1989); J. Opt. Soc. Am. B 7, 239 (1990)] is shown to
      compare favorably with these results.

PMID- 19768008
TI  - Nanosecond image processing using stimulated photon echoes.
AB  - Processing of two-dimensional images on a nanosecond time scale is demonstrated
      using the stimulated photon echoes in a rare-earth-doped crystal (0.1 at. %
      Pr(3+):LaF(3)). Two spatially encoded laser pulses (pictures) resonant with the
      (3)P(0)-(3)H(4) transition of Pr(3+) were stored by focusing the image pulses
      sequentially into the Pr(3+):LaF(3) crystal. The stored information is retrieved
      and processed by a third read pulse, generating the echo that is the spatial
      convolution or correlation of the input images. Application of this scheme to
      high-speed pattern recognition is discussed.

PMID- 19768009
TI  - High-speed surface display through hybrid processing.
AB  - We propose a high-speed surface reconstruction from three-dimensional data
      through optical-digital hybrid processing.Surface images are currently
      reconstructed through digital processing, which takes a long time mainly because
      of the rotation and interpolation of the volume data. In the proposed system,
      slice images of threedimensional volume data are optically rotated and
      interpolated. In principle, one surface image can be obtained in the video rate
      when we use the same number of sets of optical processors as slices to be
      processed. Furthermore, this system could lead to a hybrid three-dimensional
      simulator; most operations such as rotation, cutting, digging holes, and peeling
      skins are interactively achieved at the video speed. Fundamental experiments are
      described that confirm the effectiveness of this method.

PMID- 19768010
TI  - Multilevel phase holograms manufactured by electron-beam lithography.
AB  - Ten-level transmission phase holograms (kinoforms) manufactured in one resist
      layer by electron-beam lithography are reported for the first time to our
      knowledge. The measured hologram diffraction efficiencies were 70% for the two
      resist materials used. This corresponds to 82% of the maximum theoretical value
      for these holograms and is, to our knowledge, the highest reported to date.

PMID- 19768011
TI  - Frequency-offset, solid-state laser coherent Doppler velocity measurements of
      high-speed targets.
AB  - Diode-pumped, single-frequency Nd:YAG lasers were used to measure velocities of
      laser-accelerated targets over a range of 0.1 to greater than 2 km/sec. A 1-GHz
      optical heterodyne receiver was used with a tunable, frequencyoffset local
      oscillator to compensate for Doppler shifts of as much as 4 GHz.

PMID- 19768012
TI  - Electronic speckle-pattern interferometry using single-mode fibers and active
      fringe stabilization.
AB  - Optical fibers are used to provide object and reference illumination in the
      context of the electronic speckle-pattern interferometry technique. An all-fiber
      Michelson interferometer is used, with an electronic servo and a piezoelectric
      phase modulator, to obtain compensation for environmentally induced phase
      coupling into the fiber arms.

PMID- 19768013
TI  - Single-laser two-step fluorescence detection of atomic hydrogen in flames.
AB  - We describe a new single-laser, two-step fluorecence technique for detecting
      atomic hydrogen and demonstrate its application to flame measurements. This
      method provides the advantages of a previously demonstrated two-step method (two
      photon 243-nm n = 1 ? n = 2 excitation and subsequent single-photon 656-nm n = 2
      ? n = 3 excitation, by using two beams produced with two dye lasers) but with a
      much simpler experimental implementation (two-photon 243-nm n = 1 ? n = 2
      excitation and subsequent single-photon 486-nm n = 2 ? 4 excitation, by using the
      fundamental and frequency-doubled beams from a single 486-nm dye laser).

PMID- 19768014
TI  - Correlation microscope.
AB  - We have constructed a correlation microscope based on the Mirau interferometer
      configuration using a thin silicon nitride film beam splitter, and we have
      developed a method to extract the amplitude and phase information of the
      reflected signal from a sample located at the microscope object plane. An imaging
      theory for the interference microscope has been derived, which predicts
      accurately both the transverse response at a sharp edge and the range response to
      a perfect plane reflector.

PMID- 19768015
TI  - Experimental demonstration of a sensing mechanism for optical-fiber intermodal
      interference sensors.
AB  - A series of experiments in which a multimode optical fiber was forced to vibrate
      by a loudspeaker was performed to investigate the sensing mechanism of an
      integrated optical-fiber communication-sensing system. It was demonstrated that
      the sensing mechanism is predominantly pressure-induced phase modulation rather
      than modecoupling-induced power transfer in an optical fiber.

PMID- 19768016
TI  - Coherent optical fiber communications system using all-optical correlation
      processing.
AB  - We propose a point-to-point or single-ended communications technique based on
      single-mode optical fibers that uses all-optical pulse multiplexing at the
      transmitter and coherent optical correlation at the receiver. This technique
      shows potential for application to secure untappable communications, fiber local
      area networks, and optical ranging in the presence of a strong white-light
      background. The system can employ a low-coherence source, is insensitive to
      source phase noise and polarization-state rotation in the fiber link, and uses
      simple electronic threshold detection. Coherent correlation and anticorrelation
      are demonstrated experimentally, and practical requirements are examined.

PMID- 19768017
TI  - Generation and transmission of optical solitons in the gigahertz region using a
      directly modulated distributed-feedback laser diode.
AB  - We have succeeded for the first time, to our knowledge, in the generation and
      transmission of 6-24-GHz, 17-psec transform-limited solitons, using a directly
      modulated distributed-feedback laser diode with a narrow-band spectral filter and
      erbium-doped optical fiber amplifiers. The average optical power at 6 GHz from
      the erbium amplifier is greater than 10 mW, which corresponds to a peak power of
      98 mW. The peak power is already in the soliton power regime for dispersion
      shifted fibers. The solitons are transmitted over 22 km, and their original width
      can be completely preserved. The soliton-narrowing effect and high-order solitons
      that divide are also observed.

PMID- 19768018
TI  - Optimization of a thin-film multilayer design by use of the generalized simulated
      annealing method.

PMID- 19768019
TI  - Stimulated thermal Rayleigh scattering threshold induced by velocity turbulence.

PMID- 19768020
TI  - Quenching optical breakdown with an applied electric field.

PMID- 19768021
TI  - Limitation of a wedged etalon for high-resolution linewidth measurements.

PMID- 19768022
TI  - Normal-incidence reflection of slow atoms from an optical evanescent wave.

PMID- 19768024
TI  - Spatially resolved Raman study of self-organized [khgr ](2) gratings in optical
      fibers.

PMID- 19768023
TI  - Double peaks of fundamental diffraction efficiency versus biasing of electric
      fields through the degenerate four-wave mixing process in nematic liquid-crystal
      films.

PMID- 19768025
TI  - Coherent beam and image amplification by Brillouin two-beam coupling in CSS2.

PMID- 19768027
TI  - Short-pulse Q-switched 1.3- and 1-mum diode-pumped lasers.

PMID- 19768026
TI  - Coupled-mode theory for corrugated optical waveguides.

PMID- 19768028
TI  - High-resolution hyperfine spectroscopy in real space.

PMID- 19768029
TI  - Macroscopic quantum superpositions by means of single-atom dispersion.

PMID- 19768030
TI  - Ultranarrow extraresonant holes and antiholes in pump - probe and four-wave
      mixing spectroscopy of a two-level system interacting with two fields of
      arbitrary intensity.

PMID- 19768031
TI  - Single, trapped Sr+ atom: laser cooling and quantum jumps by means of the 4d2D5/2
      5s2S1/2 transition.
AB  - A single Sr+ atom was confined in a radio-frequency quadrupole trap and laser
      cooled with resonant laser light. Examination of the transition Doppler profile
      indicated an ion kinetic temperature of less than 500 mK. Quantum jumps into and
      out of the metastable 4d(2)D(5/2) level were observed by laser excitation on the
      electric-quadrupole-allowed transition from the ground state at 674 nm. The dark
      and bright periods in the strong fluorescence showed variations owing to the
      applied driving field on the electric-quadrupole transition. These results
      provide an improved determination of tau = 372 +/- 25 msec for the natural
      metastable-state lifetime.

PMID- 19768033
TI  - Simple technique for improving the resolution of the delayed self-heterodyne
      method.

PMID- 19768032
TI  - Real-time holographic associative memory using doped LiNbO3 in a phase
      conjugating resonator.

PMID- 19768034
TI  - Conditions for optimal performance of monostatic coherent laser radar.

PMID- 19768035
TI  - Experimental statistics of partially developed speckle fields.

PMID- 19768036
TI  - Fiber-optic frequency shifter with no mode change using cascaded acousto-optic
      interaction regions.

PMID- 19768037
TI  - Liquid-crystal imaging Fourier-spectrometer array.

PMID- 19768038
TI  - Temporal imaging with a time lens.

PMID- 19768039
TI  - Measurement of the polarization and phase of an optical signal by coherent
      detection.
AB  - We present a four-dimensional polarization and phase calculus that is similar to
      the Jones calculus but emphasizes the relation between polarization and phase. We
      use this calculus to prove that acombined polarization- and phase-diversity
      scheme requires at least four photodetectors. We also use this calculus to
      describe the operation principle of a novel balanced polarization and phase
      hybrid.this hybrid can be used, e.g., for the complete characterization of a
      polarization controller.

PMID- 19768040
TI  - Fluorescence imaging of CO(2)laser-heated droplets.
AB  - Distortion, ejection, shattering, and propulsion of water and ethanol droplets
      containing Rhodamine 6G dye have been photographed at different time delays after
      initiation of a CO(2) laser pulse, whichcauses explosive vaporization of the
      droplets. We have developed a fluorescence imaging technique to photograph the
      liquid-phase portion of the ejected material and the parent droplet after
      irradiation by the CO(2) laser pulse.

PMID- 19768041
TI  - Artificial dielectric polymeric waveguides: semiconductor-embedded films.
AB  - Thin (less than 2 nm) layers of semiconductor clusters (the guest material) are
      sandwiched between two polymeric films (the host material), and the light-induced
      electric and magnetic dipoles form a conditional artificial dielectric.

PMID- 19768042
TI  - Ultrafast solitary waves sustained through induced phase modulation by a
      copropagating pump.
AB  - Ultrafast pulses, with an energy lower than that required to self-sustain a
      soliton shape in the anomalous dispersion regime, may preserve their shape if an
      intense copropagating pump of a different color (i.e., in the normal dispersion
      regime) and a longer duration is present.

PMID- 19768043
TI  - High-performance integrated-optical chip for a broad range of fiber-optic gyro
      applications.
AB  - A high-performance integrated-optical device for a broad range of fiber-optic
      gyro applications is reported. The circuit contains four directional couplers and
      six phase modulators that form the fiber-loop coupler, the bias and serrodyne
      phase modulators, and an on-chip interferometric serrodyne phase detector. The
      chip was fabricated by the annealed-proton-exchange method in X-cut LiNbO(3),
      which yielded a highly polarizing guided circuit with a polarization extinction
      ratio of at least 60 dB. Other performance parameters include low half-wave
      voltages (3.5-5.5 V) at 1.3 microm and splitting and tapping directional coupler
      parameters well within the design needs required by application.

PMID- 19768044
TI  - Reflective high-finesse interferometers as effective intrapulse laser frequency
      stabilizers.
AB  - The effect of optical cavity length perturbations on the intrapulse frequency
      stability of laser cavities terminating in reflective multipass interferometers
      is investigated. We demonstrate both theoretically and experimentally, in a long
      pulse single-mode TEA CO(2) laser, that intrapulse frequency chirping can be
      strongly reduced by using relatively long high-finesse interferometers. These
      results can be applied to the design of single-mode lasers with negligible
      chirping.

PMID- 19768045
TI  - Design of 1.3-microm GaInAsP surface-emitting lasers for high-bandwidth
      operation.
AB  - Important design considerations for high-speed GaInAsP 1.3-microm surface
      emitting lasers are described. Modified rate equations for surface-emitting
      lasers and a small-signal analysis are used to calculate the frequency response
      versus the mirror reflectivity. For the structure analyzed, the results predict
      optimum reflectivities of 98% for highfrequency operation and maximum quantum
      efficiency. Strong gain-saturation effects are predicted owing to the high photon
      densities that occur in these devices. As the mirror thickness increases, the
      frequency response of the laser reduces greatly. The effect of heating is found
      to be important and is included in the analysis.

PMID- 19768046
TI  - Nd:MgO:LiNbO(3) waveguide laser and amplifier.
AB  - We report efficient operation of a channel waveguide laser and a channel
      waveguide amplifier in Nd:MgO:LiNbO(3). For the laser a cw output power of 2.9 mW
      was obtained for 23.6 mW of absorbed pump power. The absorbed pump power at
      threshold was 1.5 mW, and a slope efficiency of 13% was achieved. For the
      amplifier a small-signal gain of 7.5 dB was achieved for 22 mW of coupled pump
      power.

PMID- 19768047
TI  - Passive mode locking of a cw Nd:YLF laser with a nonlinear external coupled
      cavity.
AB  - Using an optical fiber as the nonlinear medium in an external cavity, we
      demonstrated passive mode locking of a cw Nd:YLF laser at a 1.053-microm
      wavelength. Nearly transform-limited pulses as short as 3.7 psec were obtained at
      a repetition rate of 76 MHz directly from the laser output without further
      compression. The average output power ranged from 1 to 7 W.

PMID- 19768048
TI  - Image-restoration algorithms for a fully connected architecture.
AB  - We describe the implementation of a technique for achieving image superresolution
      using a fully connected network of simple processors operating in an iterative
      mode. We show that an updating scheme can be specified that ensures convergence
      for the serial (asynchronous) updating case. With the appropriate hardware,
      parallel (synchronous) updating becomes of particular interest because of the
      potential for accelerated convergence; it is this approach that we envisage
      implementing in optical hardware. For this case also, we present a convergent
      scheme that can be related to a regularized form of the Gerchberg-Papoulis
      algorithm.

PMID- 19768049
TI  - Programmable optical threshold logic implementation with an optoelectronic
      circuit.
AB  - We demonstrate optical binary threshold logic by using an optoelectronic circuit.
      This threshold gate is in itself a logical complete set owing to the availability
      of both positive and negative weights and threshold. Furthermore, the weights and
      the threshold are optically addressed, thereby providing real-time operation.
      Experimental results demonstrate AND, OR, and MAJORITY functions and three other
      arbitrary logic functions for three input signals with a single gate.
      Applications in neural computing and two-dimensional parallel logic processing
      are discussed.

PMID- 19768050
TI  - High-efficiency, wide-bandwidth optical fanout elements in dichromated gelatin.
AB  - We have combined the flexibility of computer-generated binary holograms with the
      high optical quality of dichromated gelatin holography to fabricate a range of
      efficient, wide-bandwidth, and compact space-invariant fanout elements. Our
      approach is based on a certain novel coherent spatial filtering technique, termed
      the inverse central dark ground method, which permits the use of a binary
      amplitude hologram corresponding to the desired binaryphase profile in the object
      arm of the interferometric recording setup.

PMID- 19768051
TI  - Optical asymmetrical median filtering using gray-scale convolution kernels.
AB  - Morphological transformations such as erosion and dilation can be performed
      optically by convolving the binary input image with a binary kernel and then
      passing the result through an ideal thresholder-hardlimiter. Generalizations
      result from using gray-scale convolution kernels. It is shown that gray-scale
      kernels can be used to perform transformations similar to openings and closing
      with just one convolution instead of the ususal cascade of erosion and dilation
      normally required for these operations. Optical experimental results are
      presented.

PMID- 19768052
TI  - Reverse saturable absorption in metal cluster compounds.
AB  - We report a new family of organometallic compounds that exhibit optical limiting
      through reverse saturable absorption. The optical limiting properties of the
      metal cluster compounds HFeCo(3)(CO)(12), [NEt(4)](+)FeCo(3)(CO)(12),(-)
      HFeCo(3)(CO)(10)(PMe(3))(2) and HFeCo(3)(CO)(10)(P(C(6)H(5))(3))(2) were measured
      at 532 nm using 8-nsec pulses. Pulse narrowing from 8 to 4 nsec was observed. The
      data indicate that the optical-limiting properties are essentially independent of
      the type of counter ion substituted in the compound but dependent on the ligand
      type substitution.

PMID- 19768053
TI  - High-resolution Brillouin gain spectroscopy in fused silica.
AB  - We report what is to our knowledge the first high-resolution Brillouin gain
      spectrum in a solid. Resonances corresponding to longitudinal (compressional) and
      transverse (shear) acoustic waves in fused silica are observed with good
      resolution and a high signal-to-noise ratio. Absolute gain coefficients,
      linewidths, and Brillouin frequency shifts are measured. The agreement with
      previously measured values is good.

PMID- 19768054
TI  - Simultaneous measurements of velocity, temperature, and pressure using rapid cw
      wavelength-modulation laser-induced fluorescence of OH.
AB  - The beam from a rapid-tuning single-frequency laser was used to probe the R(1)(7)
      and R(1)(11) A(2)Sigma(+) ? X(2)II (0, 0) line pair of OH at a 45 degrees
      incident angle in a combustion-driven, supersonic free jet. Absorption line
      shapes were recorded in spatially resolved, single-point fluorescence. The
      Doppler shift, intensity ratio, and collisional broadening of the measured line
      pair were used to determine velocity, temperature, and pressure. The repetition
      rate of the measurement was 3 kHz.

PMID- 19768055
TI  - Two-dimensional imaging of OH in flames by degenerate four-wave mixing.
AB  - Degenerate four-wave mixing is used to produce two-dimensional images of OH
      distributions in atmosphericpressure flames. The phase-conjugated images from
      single laser pulses exhibit excellent signal-to-noise ratios and illustrate that
      degenerate four-wave mixing has outstanding potential as a multidimensional
      diagnostic for combustion environments.

PMID- 19768056
TI  - Polymer membrane properties and structures for membrane light modulator
      applications.
AB  - A judicious selection of polymer materials for the fabrication of a deformable
      membrane light modulator (e.g., the photoemitter membrane light modulator) will
      enhance its speed. A polymer with a low surface energy decreases the device
      response time by lowering the membrane tension that is caused by the surface
      interaction between the membrane and an adjacent dielectric surface. The material
      must also have high temperature stability. A composite structure of parylene on
      poly[bis(trifluoroethoxy)phosphazene] on SiO(x) is found to meet these
      requirements, with stability to 220 degrees C and a tension of 0.18 N/m, giving a
      potential frame rate of close to 10 kHz or a throughput of >10(10) pixels/sec.

PMID- 19768057
TI  - Transform-limited pulse generation in the gigahertz region from a gain-switched
      distributed-feedback laser diode using spectral windowing.
AB  - For the first time, to our knowledge, transform-limited and high-power picosecond
      pulses in the gigahertz region are successfully generated from a distributed
      feedback laser diode using spectral manipulation with a narrow-band Fabry-Perot
      resonator and erbium fiber amplifiers. The pulses, which before the optical
      filtering have a width of 27 psec and a spectral width of 1.24 nm, are
      transformed to transform-limited pulses with a width of 17 psec and a spectral
      width of 0.21 nm. The peak power of the pulse at a 6-GHz repetition rate is
      amplified to greater than 90 mW with an erbium fiber amplifier.

PMID- 19768058
TI  - Low-loss and low-drive-voltage electro-optical phase modulator at 10.6 microm.
AB  - We present the experimental performance of a 16-mm-long phase modulator in the
      10.6-microm wavelength range using the electro-optical effect in a InP/Ga(0.47)
      In(0.53) As-based rib waveguide. Making use of the Fabry-Perot behavior of this
      modulator due to reflections on the cleaved facets of the guide, we demonstrate a
      drive voltage lower than 100 V combined, for the first time to our knowledge in
      this range, with propagation losses of less than 1.6 dB/cm. Moreover, the
      bandwidth of this modulator is greater than 250 MHz.

PMID- 19768059
TI  - Bragg-effect grating couplers integrated in multicomponent polymeric waveguides.
AB  - A new reactive multicomponent polymeric system is presented for the real-time
      optical recording of volume phase holograms integrated in waveguiding thin films.
      Efficient Bragg-effect grating couplers are produced holographically. In a
      multimodeplanar waveguide, the input coupling efficiency reaches 62% for an
      incident 633-nm He-Ne laser beam. Almost 96% of the mode power is emitted by a
      second coupler into one single-output beam.

PMID- 19768060
TI  - Two-stage injection locking of high-power semiconductor arrays.
AB  - A new multistage diode-array injection-locking technique is demonstrated. This
      approach permits higher power extraction or higher overall gain to be achieved
      than possible with single-stage designs. Using two antireflectioncoated 40-stripe
      multiple-quantum-well diode arrays, we characterize the amplifier small-signal
      and saturated gain performance. More than 500 mWof power is achieved with single
      frequency and narrow linewidth in a nearly diffraction-limited far-field lobe.
      With small-signal inputs, an overall gain of 25 dB with 290-mW locked output is
      obtained.

PMID- 19768061
TI  - Optical bistability and multistability in an active interferometer.
AB  - Optoelectronic hybrid bistability and multistability in an active interferometer
      using a laser diode are demonstrated experimentally. The active laser-diode
      interferometer is composed of a Twyman-Green interferometer with an electronic
      feedback circuit. By feeding back the interferometer output together with an
      external light input through a detector to control thelaser-diode injection
      current, the optical bistable and multistable states of the output power from the
      laser diode are observed. Bistable operation does not require cutoff or
      saturation in the amplifier. The theoretical background of the phenomena is
      discussed.

PMID- 19768062
TI  - Active-passive mode-locked Nd:YAG laser with passive negative feedback.
AB  - Stationary ultrashort light pulses of 10-psec duration and with an energy of 10
      microJ per pulse were obtained from an active-passive mode-locked Nd:YAG laser by
      using a two-photon absorption limiter (GaAs) inserted into the resonator. The
      stability of energy in the steady-state part of the pulse train, containing
      approximately 90 pulses, is better than +/-1.5%. The dynamics of the pulse
      shortening mechanism are described, and it is shown that maximum pulse
      compression is reached after only approximately 10 round trips.

PMID- 19768063
TI  - Subpicosecond pulse generation from a Nd:glass laser using a nonlinear external
      cavity.
AB  - An actively mode-locked, continuous-wave Nd:glass laser pumped by a krypton laser
      at 0.8 microm has been coupled to a nonlinear external resonator. The 20-psec
      pulses produced by active mode locking are shortened to less than 1 psec with the
      nonlinear external cavity feedback. Subpicosecond pulse generation has been
      achieved at a pump power as low as 500 mW.

PMID- 19768064
TI  - Speckle reduction in synthetic-aperture-radar imagery.
AB  - Speckle appearing in synthetic-aperture-radar images degrades the information
      contained in these images. Speckle noise can be suppressed by adapted local
      processing techniques, permitting the definition of statistical parameters inside
      a small window centered on each pixel of the image. Two processing algorithms are
      examined; the first one uses the intensity as a variable, and the second one
      works on a homomorphic transformation of the image intensity. A statistical model
      for speckle noise that takes into account correlation in multilook imagery has
      been used to develop these processing algorithms. Several experimental results of
      processed Seasat-A syntheticaperture-radar images are discussed.

PMID- 19768065
TI  - Spatial amplification: an image-processing technique using the selective
      amplification of spatial frequencies.
AB  - A novel technique of processing optical images that we call spatial amplification
      is proposed and demonstrated. The basic idea is to amplify coherently a set of
      selected spatial frequency components of an image. Unlike in the usual spatial
      filtering techniques, in which the components are selectively blocked out at the
      Fourier plane of a coherent processor, spatial amplification does not discard any
      of the incident image information. The advantages of the proposed technique over
      spatial filtering include high energy efficiency and the possibility for
      cascading several stages. In the demonstrated experiments, the required
      amplification is provided by two-beam energy coupling in a photorefractive
      BaTiO(3) crystal with a nonuniform pump beam.

PMID- 19768066
TI  - Measurement of atmospheric aerosol extinction profiles with a Raman lidar.
AB  - A method is presented that permits the determination of atmospheric aerosol
      extinction profiles from measured Raman lidar signals. No critical input
      parameters are needed, which could cause large uncertainties of the solution, as
      is the case in the Klett method for the inversion of elastic lidar returns.

PMID- 19768067
TI  - Optical flip-flop based on parallel-connected AlGaAs/GaAs pnpn structures.
AB  - An optical flip-flop using parallel-connected pnpn (thyristor) structures is
      demonstrated for the first time to our knowledge. We utilize the differential
      optical switching technique for inverting the state of the flip-flop and the slow
      dissipation of carriers stored in the gate layers of pnpn structures for
      retaining the state. The flip-flop operation with 7.2 pJ of optical input energy
      was attained by using an AlGaAs/GaAs device. The expansibility to monolithic two
      dimensional arrays, the high on-off contrast, and the high optical gain of the
      flip-flop are useful in the design and fabrication of optical parallel processing
      systems.

PMID- 19768068
TI  - Nonlinear amplifying loop mirror.
AB  - A novel device arrangement for all-optical switching that permits efficient
      exploitation of waveguide nonlinearities is discussed. It is based on a long
      optical fiber loop mirror with an integral short asymmetrically located optical
      amplifier. The device performance is demonstrated by using a Nd(3+)-doped fiber
      amplifier. Switching is obtained for peak signal powers of less than 1 W and an
      amplifier pump power of 10 mW.

PMID- 19768069
TI  - Corner-cube retroreflectors for optical chip-to-chip interconnections.
AB  - Corner-cube retroreflectors with the dihedral angles slightly different from a
      right angle are proposed for optical chip-to-chip interconnections. The spot
      pattern of the corner cube may follow the shift of the source and is
      approximately invariant to the incident angle. This retroreflective property
      substantially reduces the requirement for alignment accuracy. The design of a
      corner cube for given source and image positions using a ray-tracing algorithm
      and iteration procedure is presented.

PMID- 19768070
TI  - Acoustic instability induced in compressible, transparent fluids by
      electrostrictive effects.
AB  - If the electromagnetic energy density of the incident high-energy laser beam is
      sufficiently high, an instability is induced in an irradiated, compressible fluid
      by electrostrictive effects. The physical basis of this instability is that a
      dielectric fluid flows toward a region of high-energy density, countering the
      usual tendency of a fluid to flow from a region of higher to lower pressure. An
      observable signature of this instability is calculated. This instability can
      occur in water droplets that are irradiated by a high-energy laser beam.

PMID- 19768071
TI  - Coherence properties of retroreflected radiation in a power-law random medium.
AB  - The presence of random refractive-index fluctuations in location and remote
      sensing experiments and double passage of the scattered radiation through the
      same random inhomogeneities as the incident radiation results in new statistical
      effects not observed along one-directional paths. To account for the correlation
      of the forward-backward propagating events, there is a need for a measure in
      which the random information along the propagation path is preserved. For
      generation of the even statistical moments, the relevant measure defined in the
      recently formulated stochastic geometrical theory of diffraction is the two-point
      random function. We present approximate analytical solutions for the high
      frequency propagators based on the multiscale expansion asymptotic procedure
      applied to the stochastic partial differential equation governing the propagation
      of the two-point random fluctuation. Analysis of the correlation properties of
      the retroreflected plane wave is presented for a random medium characterized by a
      Kolmogorovian refractive-index fluctuation spectrum.

PMID- 19768072
TI  - Integrated-optical array generator.
AB  - We demonstrate an optical system that splits one laser beam into an array of N x
      N equal-intensity beams. It consists of a grating and a diffractive lens, which
      are integrated on one side of a single planar quartz-glass substrate. The grating
      and the lens are fabricated with multiple discrete phase levels by using
      photolithography and thin-film deposition.

PMID- 19768073
TI  - Photoacoustic generation of anisotropic pressure waves through photodissociation
      of Cl(2).
AB  - Photodissociation of diatomic molecules by linearly polarized radiation in
      general produces an anisotropic distribution of recoiling atomic fragments. When
      a short burst of radiation dissociates a gas at low pressure, the collective
      linear momenta of the individual recoiling photofragments add at any point in
      space to act as a macroscopic pressure wave, the impulse corresponding to which
      can be detected by a sensitive microphone. We report here detection of
      anisotropic pressure waves from photodissociation of Cl(2) with 355-nm radiation.
      The experimental data show the pressure wave to be peaked in a direction
      perpendicular to the polarization direction of the incident radiation, indicating
      a predominantly perpendicular transition moment in Cl(2) at this wavelength.

PMID- 19768074
TI  - Amplitude-modulated interferometry.
AB  - Specific modulating procedures of the interfering amplitudes in a double-beam
      interferometer lead to highprecision measurements and insensitivity to changes in
      reflectivity. The performance of such an interferometer is superior to that of a
      phase-shifting interferometer because the modulated quantity is the amplitude
      rather than the phase, which is the measured quantity. This system is easier to
      implement and may be operated faster.

PMID- 19768075
TI  - High-reflectivity phase conjugation using Brillouin preamplification.
AB  - We describe experiments in which a weak laser pulse is phase conjugated by using
      a high-gain Brillouin amplifier in front of a stimulated Brillouin scattering
      phase-conjugate mirror. We observe phase conjugation with signal energies as low
      as 3 x 10(-13) J and with a maximum reflection coefficient of 2 x 10(8).

PMID- 19768076
TI  - Diffractive parametric imaging in uniaxial crystals.
AB  - We derive the diffractive transfer functions in uniaxial crystals for the
      parametric processes of upconversion and downconversion with an undepleted plane
      wave pump. This description is for Type I or Type II phase matching in either
      positive or negative uniaxial crystals. Our results agree closely with an
      experiment in KD*P in which the pump, signal, and idler wavelengths are 1.064,
      1.064, and 0.532 , microm and the polarizations are extraordinary, ordinary, and
      extraordinary, respectively. We show that the idler output intensity is a
      slightly elliptical ring displaced from the ordinary ray in the direction of the
      Poynting vector walk-off. The experimental and theoretical spatial frequencies
      describing the position of the idler intensity ellipse agree closely.

PMID- 19768077
TI  - Direct measurement of the transverse velocity of dark spatial solitons.
AB  - We describe the direct experimental measurement of the transverse propagation
      velocities of dark spatial solitons. Good agreement is obtained from a comparison
      of the velocities measured experimentally and the velocities predicted by the two
      dimensional theory of Zakharov and Shabat [Sov. Phys. JETP 37, 823 (1973)].

PMID- 19768078
TI  - Polarimetric coherence multiplexing using high-birefringence optical-fiber
      sensors and short coherence sources.
AB  - We describe a polarimetric coherence multiplexed system that uses a source with a
      short coherence length to reduce the effect of cross talk and of phase-induced
      intensity noise. The system is constructed with sections of highbirefringence
      optical fibers, which allow the differential path lengths to be matched within
      micrometer accuracy. A minimum detectable phase sensitivity of 3 microrad/
      radicalHz has been demonstrated.

PMID- 19768079
TI  - Characteristics of optical waveguides made by electric-field-assisted K(+)-ion
      exchange.
AB  - Planar optical waveguides were fabricated by using an electric-field-assisted
      potassium-ion exchange in soda-lime glass substrates. Mode index measurements for
      both the TE and TM modes were made for the purpose of establishing formulas for
      the effective diffusion constant, guide depth, and refractive-index change, given
      the electric field, the diffusion temperature, and the time. The index profile
      could be accurately modeled by a modified Fermi function, with significant
      improvement over the step-index model.

PMID- 19768081
TI  - Long-pulse excimer integrated master-oscillator-power-amplifier optical cavity.
AB  - The performance of an integrated master-oscillator-power-amplifier optical cavity
      to extract polarized, linenarrowed, tunable, and near-diffraction-limited
      radiation efficiently from a long-pulse wide-aperture electric discharge XeCl
      excimer laser is described. Pulse energies of 600 mJ with signal purity exceeding
      95% have been achieved from a single laser.

PMID- 19768080
TI  - Silicon antiresonant reflecting optical waveguides.
AB  - A new silicon waveguide called ARROW-C is proposed and analyzed at the 1.3-microm
      wavelength. The silicon structure uses two buried layers of SiO(2) or beta-SiC
      with a thickness of 14-23 nm to permit optical tunneling for leakymode
      propagation. A propagation loss of ~0.5 dB/cm is predicted for the TE(0) or the
      TM(0) mode in a 5-microm-thick Sicore layer. Novel silicon ARROW-A and ARROW-B
      guides are also discussed. The former uses a pair of buried GeSi layers; the
      latter employs buried SiO(2) and GeSi films.

PMID- 19768082
TI  - Vanadium-pumped titanium x-ray laser.
AB  - A new laboratory x-ray laser is described that is resonantly photopumped by two
      3d ? 2p emission lines in fluorinelike vanadium (Z = 23) and lases on several 3p
      ? 3s transitions in neonlike titanium (Z = 22). Calculations show that five of
      the laser lines have gains greater than 5 cm(-1) for reasonable values of the
      pump lines, with the shortest wavelength of the five being at 32.65 nm.

PMID- 19768083
TI  - Threshold current of extremely narrow semiconductor quantum-well lasers.
AB  - The threshold current of extremely narrow semiconductor quantum-well lasers is
      calculated, accounting for the reduced lateral optical filling factor and the
      gain saturation in the quantum well. It is shown that the reduced optical filling
      factor leads to a minimum in the threshold current at an optimum value of the
      quantum-well width. Analytic approximations of the optimal width and length of
      the laser cavity are derived. In addition, it is shown that two-dimensional
      separate-confinement quantum-well heterostructures can reduce the threshold
      current, particularly in the case of quantum-wire lasers.

PMID- 19768084
TI  - Passive laser mode locking with an antiresonant nonlinear mirror.
AB  - A nonlinear mirror that is based on an antiresonant ring incorporating a
      nonlinear element sensitive to the polarization state of the circulating light
      has been developed. No phase matching of the mirror to the laser cavity is
      necessary, so the mirror does not need active length stabilization. Spontaneous
      mode locking occurs when the mirror is incorporated into a cw Nd:YAG laser.
      Pulses of 11-psec duration are produced at 1064 nm; two output beams at 532 nm
      are also generated. An analysis indicates that the primary mechanism responsible
      for passive mode locking is self-phase modulation in the nonlinear element.

PMID- 19768085
TI  - Phase-only filters with maximally sharp correlation peaks.
AB  - A performance measure called the peak-to-correlation energy is used to
      characterize the sharpness of correlation outputs. This measure is then used to
      determine the phase-only filter with maximally sharp correlation peaks.

PMID- 19768086
TI  - Binary Fourier phase-only correlation.
AB  - A technique called binary Fourier phase-only correlation is proposed for an
      incoherent-optical-digital-electric hybrid system. This technique has the
      advantages of high discriminant ability, a small memory area, and a short
      processing time. This technique is applicable to digital computing systems.

PMID- 19768087
TI  - Cesium frequency standard for lasers at lambda = 1.06 microm.
AB  - High-resolution spectra of the X(1)Sigma(+)(g)-A(1)Sigma(+)(u) band of molecular
      cesium at lambda = 1.06 microm have been measured. An absolute wave-number
      reference table for lasers emitting at lambda = 1.06 microm has been established.
      The cesium resonances are calibrated with respect to the well-known molecular
      iodine absorption lines at lambda = 0.53 microm. An accuracy of 10(-7) has been
      achieved.

PMID- 19768088
TI  - Doppler-free two-photon-excited fluorescence spectroscopy of atomic hydrogen in
      flames.
AB  - We describe Doppler-free 205-nm two-photon excitation studies of atomic hydrogen
      performed using a single-mode pulsed dye-laser system in low-pressure flames.
      Excitation spectra confirm calculated line-strength ratios for transitions to the
      3S and 3D states. Collisional broadening rates are obtained in several flames and
      compared with quenching rates measured in the same flames, using time-resolved
      fluorescence measurements.

PMID- 19768089
TI  - Periodically refreshed multiply exposed photorefractive holograms.
AB  - We describe a method for increasing the diffraction efficiency of multiply
      exposed photorefractive holograms by periodic copying. The method is
      experimentally demonstrated with photorefractive and thermoplastic recording
      media.

PMID- 19768090
TI  - Optical aberration correction by real-time holography in liquid crystals.
AB  - We present results of experiments that use nematic-phase liquid crystal as a real
      time holographic recording medium. Plane-wave gratings were written with as
      little as 10 mJ/cm(2) of incident write-beam energy from a pulsed Nd:YAG laser,
      and diffraction efficiencies greater than 25% were measured at 633 nm. Grating
      decay times were observed to fall within two distinct time regimes: a rapid-decay
      time of 60 to 100 microsec and a slower-decay time of 6 to 30 msec. The rapid
      decay regime was used to demonstrate real-time correction of severely aberrated
      images by degenerate four-wave mixing.

PMID- 19768091
TI  - Experimental demonstration of a Raman scattering detector based on laser-enhanced
      ionization.
AB  - We report what is to our knowledge the first experimental demonstration of
      detection of Raman photons by means of laser-enhanced ionization of magnesium
      atoms in an air-acetylene flame. A frequency-doubled dye laser was directed into
      a cell containing carbon tetrachloride. The resulting Stokes Raman photons were
      transferred into the flame, where they excited the magnesium atomic vapor into
      the 3p(1)P(1) state. The excited atoms were then pumped by another laser into the
      5d(1)D(2) state, from which efficient collisional ionization occurred. We
      estimate a quantum efficiency of approximately 50% for the detector.

PMID- 19768092
TI  - Flame front imaging in an internal-combustion engine simulator by laser-induced
      fluorescence of acetaldehyde.
AB  - Acetaldehyde has been used as a fluorescent dopant for two-dimensional imaging of
      the flame front in an internalcombustion-engine simulator. The molecule was
      excited with a XeCl-laser-light sheet at 308 nm, and broadband fluorescence
      centered at 400 nm was detected. In this way, the flame front could be marked by
      mapping regions of unburned gas. Also, the intake process into the engine could
      be followed.

PMID- 19768093
TI  - Photoinduced second-harmonic generation in gamma-ray-irradiated optical fibers.
AB  - The effect of gamma-ray irradiation on photoinduced second-harmonic generation in
      optical fibers is investigated for the first time to our knowledge. A significant
      increase (by a factor of 20) in the conversion efficiency of gamma-ray-irradiated
      optical fibers is found. An explanation of the experimental results is suggested,
      which is based on the photovoltaic mechanism of the photoinduced second-harmonic
      generation.

PMID- 19768094
TI  - Axial birefringence due to intense electromagnetic fields: electric and magnetic
      rectification.
AB  - The Maxwell equation is solved for axial birefringence due to electric and
      magnetic rectification measured with a collinear unpolarized probe laser by
      switching an intense circularly polarized pump laser from right to left. Axial
      birefringence is caused by vector products of electric and magnetic conjugate
      components of the intense electromagnetic field. Axial birefringence can be
      measured with a modified Rayleigh refractometer and depends on new three-and four
      rank molecular property tensors.

PMID- 19768095
TI  - Regenerative pulse amplification in the 10-kHz range.
AB  - A continuously pumped Nd:YLF regenerative amplifier has been developed that can
      amplify 40-psec pulses at a repetition rate of greater than 10 kHz, with an
      average power in excess of 5 W. Pulse energies are as high as 2.0 mJ at 3 kHz and
      640 microJ at 10.5 kHz. The limitation on the amplifier repetition rate that is
      associated with piezoelectric ringing in LiNbO(3) electro-optics has been
      overcome by using short-pulsed electric fields (10 nsec) and proper acoustic
      damping. Regenerative pulse amplification, limited in repetition only by the pump
      rate of the gain medium, has been achieved. The high repetition rate in
      regenerative pulse amplification made possible by this development should prove
      important for signal-processing considerations in a wide variety of pulse
      amplification applications.

PMID- 19768096
TI  - Gain in erbium-doped fiber amplifiers: a simple analytical solution for the rate
      equations.
AB  - The solution of the rate equations that describe an erbium-doped fiber amplifier
      is investigated, and the possibility of obtaining an analytical solution for
      several field and erbium transverse distributions in the active fiber is
      determined. With the obtained equations it is possible to find directly the
      signal gain and the main parameters that influence it. The validity of this
      research is extended to the case of high signal power.

PMID- 19768097
TI  - High-repetition-rate terawatt excimer laser system with gated gain amplification.
AB  - A high-repetition-rate (10-Hz), terawatt excimer laser system was developed by
      using a discharged-pumped, wide-aperture (6 cm x 4 cm) amplifier. A new scheme of
      gated gain amplification was applied to the final stage for the increase of the
      output energy along with the suppression of the amplified spontaneous emission.
      An output energy of 410 mJ was obtained with a pulse width of 280 fsec and an
      amplified spontaneous emission of 10%, resulting in a peak power of 1.5 TW by two
      beams. The beam was focused by an off-axis parabolic mirror to a spot size of 2.3
      microm x 2.4 microm.

PMID- 19768098
TI  - Continuous-wave, pair-pumped laser.
AB  - We report room-temperature operation of what we believe is the first continuous
      wave laser that relies exclusively on cooperative upconversion by coupled ion
      pairs to achieve population inversion.

PMID- 19768099
TI  - Picosecond pulse generation from a continuous-wave diode laser through cross
      phase modulation in an optical fiber.
AB  - Picosecond pulses have been generated from a cw diode-laser source using cross
      phase modulation from a cw-pumped mode-locked Nd:YAG laser operating at 1.06
      microm. By tuning the diode laser in the region near 1.5 microm, the effect of
      group-velocity mismatch can be minimized, making efficient use of the fiber
      length and optimizing the cross-phase modulation spectral broadening.

PMID- 19768100
TI  - Filter design for optical pattern recognition: multicriteria optimization
      approach.
AB  - A method of constructing optimal multicriteria filters for optical pattern
      recognition is presented. In the particular case of synthetic discriminant
      function filters, this method is illustrated for double-optimization criteria,
      and filters that are not overspecialized are obtained, in contrast with
      traditional techniques. Furthermore, a rigorous comparison between different
      filters, with respect to the considered criteria, is provided with this approach.

PMID- 19768101
TI  - Imaging after double passage through a random screen.
AB  - The average intensity spectrum is derived for an object illuminated and viewed
      through the same random screen. This double passage is shown to give an average
      image that contains diffraction-limited information about the Fourier modulus of
      the object amplitude.

PMID- 19768102
TI  - Optical outer-product learning in a neural network using optically stimulable
      phosphor.
AB  - A novel application of optically stimulable phosphor (OSP) to a memory device for
      modifiable synaptic weights in a learnable optical neural network is
      experimentally demonstrated. OSP has many attractive features for mass storage of
      synaptic weight; it is analog, accessible in parallel, erasable and rewritable,
      high in resolution, and fast in response.

PMID- 19768103
TI  - Optical neural network with pocket-sized liquid-crystal televisions.
AB  - A compact optical neural network that uses high-resolution liquid-crystal
      televisions has been constructed. System design considerations and an
      experimental demonstration of the liquid-crystal television neural network are
      reported.

PMID- 19768104
TI  - Surface-plasmon-enhanced multiphoton photoelectric emission from thin silver
      films.
AB  - We report the enhancement of multiphoton photoelectric emission, from a thin
      silver film, by surface plasmons excited at the single-metal-vacuum interface.
      The surface plasmons are resonantly pumped by femtosecond laser pulses in the
      Kretchmann attenuated-total-internal-reflection configuration. A quantum yield
      approaching 2 x 10(-8) at a photon fluence of 10 MW/cm (2) from a two-photon
      process was observed, which is 5 x 10(3) higher than that of the bulk emission
      measured for the same film at the same power fluence.

PMID- 19768105
TI  - Submicrometer lithography using lensless high-efficiency holographic systems.
AB  - A hologram recording geometry that was total internal reflection of the reference
      and reconstruction beams from a photosensitive material surface is used to
      achieve 0.5-microm resolution at lambda = 457 nm in the readout of a
      reconstructed image on a photoresist. Such a geometry has demonstrated stable
      image quality for parallel displacement within the illuminated area and
      diffraction efficiency tolerance within a +/-2 degrees tilt about the axis of the
      reconstruction beam. The total-internal-reflection recording system provides
      double-fringe sets for each plane component inside the volume hologram;
      therefore, a diffraction efficiency as high as 80% was observed. The result is
      applicable to highvolume submicrometer lithography and can be expanded to a 20-cm
      (8-in.) semiconductor submicrometer pattern. The use of a large-aperture, well
      collimated laser beam provides us with much higher throughput than that of
      existing lithography machines.

PMID- 19768106
TI  - Droplet sizing in fuel injections by stimulated Raman scattering.
AB  - It is often difficult to distinguish between morphology-dependent resonance and
      Raman intensity features in nonlinear Raman spectra of organic fuel droplets. In
      theory the morphology-dependent resonances can be deconvoluted from single-shot
      spectra, but in practice this is difficult because of shot-to-shot parameter
      variation. Frequency-analysis methods have been applied to spectra obtained from
      fuel sprays, and correlation analysis is found to be quick and easily
      interpreted.

PMID- 19768107
TI  - Cytology by Infrared Micro-Spectroscopy: Automatic Distinction of Cell Types in
      Urinary Cytology.
AB  - We report microscopically collected infrared spectra of cells found in human
      urine in an effort to develop automatic methods for bladder cancer screening.
      Unsupervised multivariate analysis of the observed spectral patterns reveals
      distinct spectral classes, which correlated very well with visual cytology.
      Therefore, we believe that spectral analysis of individual cells can aid cytology
      in rendering reliable diagnoses based on objective measurements and discriminant
      algorithms.

PMID- 19768108
TI  - Correlated Optical Spectroscopy and Transmission Electron Microscopy of
      Individual Hollow Nanoparticles and their Dimers.
AB  - The optical spectra of individual Ag-Au alloy hollow particles were correlated
      with the particles' structures obtained by transmission electron microscopy
      (TEM). The TEM provided direct experimental access to the dimension of the
      cavity, thickness of the metal shell, and the interparticle distance of hollow
      particle dimers with high spatial resolution. The analysis of correlated spectral
      and structural information enabled the quantification of the influence of the
      core-shell structure on the resonance energy, plasmon lifetime, and plasmon
      coupling efficiency. Electron beam exposure during TEM inspection was observed to
      affect plasmon wavelength and lifetime, making optical inspection prior to
      structural characterization mandatory.

PMID- 19768109
TI  - Determinants of leukocyte margination in rectangular microchannels.
AB  - Microfabrication of polydimethylsiloxane (PDMS) devices has provided a new set of
      tools for studying fluid dynamics of blood at the scale of real microvessels.
      However, we are only starting to understand the power and limitations of this
      technology. To determine the applicability of PDMS microchannels for blood flow
      analysis, we studied white blood cell (WBC) margination in channels of various
      geometries and blood compositions. We found that WBCs prefer to marginate
      downstream of sudden expansions, and that red blood cell (RBC) aggregation
      facilitates the process. In contrast to tubes, WBC margination was restricted to
      the sidewalls in our low aspect ratio, pseudo-2D rectangular channels and
      consequently, margination efficiencies of more than 95% were achieved in a
      variety of channel geometries. In these pseudo-2D channels blood rheology and
      cell integrity were preserved over a range of flow rates, with the upper range
      limited by the shear in the vertical direction. We conclude that, with certain
      limitations, rectangular PDMS microfluidic channels are useful tools for
      quantitative studies of blood rheology.

PMID- 19768110
TI  - Linking chronic infection and autoimmune diseases: Mycobacterium avium subspecies
      paratuberculosis, SLC11A1 polymorphisms and type-1 diabetes mellitus.
AB  - BACKGROUND: The etiology of type 1 diabetes mellitus (T1DM) is still unknown;
      numerous studies are performed to unravel the environmental factors involved in
      triggering the disease. SLC11A1 is a membrane transporter that is expressed in
      late endosomes of antigen presenting cells involved in the immunopathogenic
      events leading to T1DM. Mycobacterium avium subsp. paratuberculosis (MAP) has
      been reported to be a possible trigger in the development of T1DM.
      METHODOLOGY/PRINCIPAL FINDINGS: Fifty nine T1DM patients and 79 healthy controls
      were genotyped for 9 polymorphisms of SLC11A1 gene, and screened for the presence
      of MAP by PCR. Differences in genotype frequency were evaluated for both T1DM
      patients and controls. We found a polymorphism in the SLC11A1 gene (274C/T)
      associated to type 1 diabetic patients and not to controls. The presence of MAP
      DNA was also significantly associated with T1DM patients and not with controls.
      CONCLUSIONS/SIGNIFICANCE: The 274C/T SCL11A1 polymorphism was found to be
      associated with T1DM as well as the presence of MAP DNA in blood. Since MAP
      persists within macrophages and it is also processed by dendritic cells, further
      studies are necessary to evaluate if mutant forms of SLC11A1 alter the processing
      or presentation of MAP antigens triggering thereby an autoimmune response in T1DM
      patients.

PMID- 19768111
TI  - Loss of RhoB expression enhances the myelodysplastic phenotype of mammalian
      diaphanous-related Formin mDia1 knockout mice.
AB  - Myelodysplastic syndrome (MDS) is characterized by ineffective hematopoiesis and
      hyperplastic bone marrow. Complete loss or interstitial deletions of the long arm
      of chromosome 5 occur frequently in MDS. One candidate tumor suppressor on 5q is
      the mammalian Diaphanous (mDia)-related formin mDia1, encoded by DIAPH1 (5q31.3).
      mDia-family formins act as effectors for Rho-family small GTP-binding proteins
      including RhoB, which has also been shown to possess tumor suppressor activity.
      Mice lacking the Drf1 gene that encodes mDia1 develop age-dependent
      myelodysplastic features. We crossed mDia1 and RhoB knockout mice to test whether
      the additional loss of RhoB expression would compound the myelodysplastic
      phenotype. Drf1(-/-)RhoB(-/-) mice are fertile and develop normally. Relative to
      age-matched Drf1(-/-)RhoB(+/-) mice, the age of myelodysplasia onset was earlier
      in Drf1(-/-)RhoB(-/-) animals--including abnormally shaped erythrocytes,
      splenomegaly, and extramedullary hematopoiesis. In addition, we observed a
      statistically significant increase in the number of activated
      monocytes/macrophages in both the spleen and bone marrow of Drf1(-/-)RhoB(-/-)
      mice relative to Drf1(-/-)RhoB(+/-) mice. These data suggest a role for RhoB
      regulated mDia1 in the regulation of hematopoietic progenitor cells.

PMID- 19768113
TI  - Disentangling vector-borne transmission networks: a universal DNA barcoding
      method to identify vertebrate hosts from arthropod bloodmeals.
AB  - Emerging infectious diseases represent a challenge for global economies and
      public health. About one fourth of the last pandemics have been originated by the
      spread of vector-borne pathogens. In this sense, the advent of modern molecular
      techniques has enhanced our capabilities to understand vector-host interactions
      and disease ecology. However, host identification protocols have poorly profited
      of international DNA barcoding initiatives and/or have focused exclusively on a
      limited array of vector species. Therefore, ascertaining the potential afforded
      by DNA barcoding tools in other vector-host systems of human and veterinary
      importance would represent a major advance in tracking pathogen life cycles and
      hosts. Here, we show the applicability of a novel and efficient molecular method
      for the identification of the vertebrate host's DNA contained in the midgut of
      blood-feeding arthropods. To this end, we designed a eukaryote-universal forward
      primer and a vertebrate-specific reverse primer to selectively amplify 758 base
      pairs (bp) of the vertebrate mitochondrial Cytochrome c Oxidase Subunit I (COI)
      gene. Our method was validated using both extensive sequence surveys from the
      public domain and Polymerase Chain Reaction (PCR) experiments carried out over
      specimens from different Classes of vertebrates (Mammalia, Aves, Reptilia and
      Amphibia) and invertebrate ectoparasites (Arachnida and Insecta). The analysis of
      mosquito, culicoid, phlebotomie, sucking bugs, and tick bloodmeals revealed up to
      40 vertebrate hosts, including 23 avian, 16 mammalian and one reptilian species.
      Importantly, the inspection and analysis of direct sequencing electropherograms
      also assisted the resolving of mixed bloodmeals. We therefore provide a universal
      and high-throughput diagnostic tool for the study of the ecology of
      haematophagous invertebrates in relation to their vertebrate hosts. Such
      information is crucial to support the efficient management of initiatives aimed
      at reducing epidemiologic risks of arthropod vector-borne pathogens, a priority
      for public health.

PMID- 19768112
TI  - BRCA1 interacts with Smad3 and regulates Smad3-mediated TGF-beta signaling during
      oxidative stress responses.
AB  - BACKGROUND: BRCA1 is a key regulatory protein participating in cell cycle
      checkpoint and DNA damage repair networks. BRCA1 plays important roles in
      protecting numerous cellular processes in response to cell damaging signals.
      Transforming growth factor-beta (TGF-beta) is a potent regulator of growth,
      apoptosis and invasiveness of tumor cells. TFG-beta activates Smad signaling via
      its two cell surface receptors, the TbetaRII and ALK5/TbetaRI, leading to Smad
      mediated transcriptional regulation. METHODOLOGY/PRINCIPAL FINDINGS: Here, we
      report an important role of BRCA1 in modulating TGF-beta signaling during
      oxidative stress responses. Wild-type (WT) BRCA1, but not mutated BRCA1 failed to
      activate TGF-beta mediated transactivation of the TGF-beta responsive reporter,
      p3TP-Lux. Further, WT-BRCA1, but not mutated BRCA1 increased the expression of
      Smad3 protein in a dose-dependent manner, while silencing of WT-BRCA1 by siRNA
      decreased Smad3 and Smad4 interaction induced by TGF-beta in MCF-7 breast cancer
      cells. BRCA1 interacted with Smad3 upon TGF-beta1 stimulation in MCF-7 cells and
      this interaction was mediated via the domain of 298-436aa of BRCA1 and Smad3
      domain of 207-426aa. In addition, H(2)O(2) increased the colocalization and the
      interaction of Smad3 with WT-BRCA1. Interestingly, TGF-beta1 induced Smad3 and
      Smad4 interaction was increased in the presence of H(2)O(2) in cells expressing
      WT-BRCA1, while the TGF-beta1 induced interaction between Smad3 and Smad4 was
      decreased upon H(2)O(2) treatment in a dose-dependent manner in HCC1937 breast
      cancer cells, deficient for endogenous BRCA1. This interaction between Smad3 and
      Smad4 was increased in reconstituted HCC1937 cells expressing WT-BRCA1
      (HCC1937/BRCA1). Further, loss of BRCA1 resulted in H(2)O(2) induced nuclear
      export of phosphor-Smad3 protein to the cytoplasm, resulting decreased of Smad3
      and Smad4 interaction induced by TGF-beta and in significant decrease in Smad3
      and Smad4 transcriptional activities. CONCLUSIONS/SIGNIFICANCE: These results
      strongly suggest that loss or reduction of BRCA1 alters TGF-beta growth
      inhibiting activity via Smad3 during oxidative stress responses.

PMID- 19768114
TI  - Causes of abnormal Ca2+ transients in Guinea pig pathophysiological ventricular
      muscle revealed by Ca2+ and action potential imaging at cellular level.
AB  - BACKGROUND: Abnormal Ca(2+) transients are often observed in heart muscles under
      a variety of pathophysiological conditions including ventricular tachycardia. To
      clarify whether these abnormal Ca(2+) transients can be attributed to abnormal
      action potential generation or abnormal Ca(2+) handling/excitation-contraction
      (EC) coupling, we developed a procedure to determine Ca(2+) and action potential
      signals at the cellular level in isolated heart tissues. METHODOLOGY/PRINCIPAL
      FINDINGS: After loading ventricular papillary muscle with rhod-2 and di-4-ANEPPS,
      mono-wavelength fluorescence images from rhod-2 and ratiometric images of two
      wavelengths of emission from di-4-ANEPPS were sequentially obtained. To mimic the
      ventricular tachycardia, the ventricular muscles were field-stimulated in non
      flowing Krebs solution which elicited abnormal Ca(2+) transients. For the failed
      and alternating Ca(2+) transient generation, there were two types of causes,
      i.e., failed or abnormal action potential generation and abnormal EC coupling. In
      cells showing delayed initiation of Ca(2+) transients with field stimulation,
      action potential onset was delayed and the rate of rise was slower than in
      healthy cells. Similar delayed onset was also observed in the presence of
      heptanol, an inhibitor of gap junction channels but having a non-specific channel
      blocking effect. A Na(+) channel blocker, on the other hand, reduced the rate of
      rise of the action potentials but did not result in desynchronization of the
      action potentials. The delayed onset of action potentials can be explained
      primarily by impaired gap junctions and partly by Na(+) channel inactivation.
      CONCLUSIONS/SIGNIFICANCE: Our results indicate that there are multiple patterns
      for the causes of abnormal Ca(2+) signals and that our methods are useful for
      investigating the physiology and pathophysiology of heart muscle.

PMID- 19768115
TI  - Restriction of HIV-1 replication in monocytes is abolished by Vpx of SIVsmmPBj.
AB  - BACKGROUND: Human primary monocytes are refractory to infection with the human
      immunodeficiency virus 1 (HIV-1) or transduction with HIV-1-derived vectors. In
      contrast, efficient single round transduction of monocytes is mediated by vectors
      derived from simian immunodeficiency virus of sooty mangabeys (SIVsmmPBj),
      depending on the presence of the viral accessory protein Vpx. METHODS AND
      FINDINGS: Here we analyzed whether Vpx of SIVsmmPBj is sufficient for
      transduction of primary monocytes by HIV-1-derived vectors. To enable
      incorporation of PBj Vpx into HIV-1 vector particles, a HA-Vpr/Vpx fusion protein
      was generated. Supplementation of HIV-1 vector particles with this fusion protein
      was not sufficient to facilitate transduction of human monocytes. However,
      monocyte transduction with HIV-1-derived vectors was significantly enhanced after
      delivery of Vpx proteins by virus-like particles (VLPs) derived from SIVsmmPBj.
      Moreover, pre-incubation with Vpx-containing VLPs restored replication capacity
      of infectious HIV-1 in human monocytes. In monocytes of non-human primates,
      single-round transduction with HIV-1 vectors was enabled. CONCLUSION: Vpx
      enhances transduction of primary human and even non-human monocytes with HIV-1
      derived vectors, only if delivered in the background of SIVsmmPBj-derived virus
      like particles. Thus, for accurate Vpx function the presence of SIVsmmPBj capsid
      proteins might be required. Vpx is essential to overcome a block of early
      infection steps in primary monocytes.

PMID- 19768116
TI  - Inactivation of aPKClambda reveals a context dependent allocation of cell
      lineages in preimplantation mouse embryos.
AB  - BACKGROUND: During mammalian preimplantation development, lineage divergence
      seems to be controlled by the interplay between asymmetric cell division (once
      cells are polarized) and positional information. In the mouse embryo, two
      distinct cell populations are first observed at the 16-cell stage and can be
      distinguished by both their position (outside or inside) and their phenotype
      (polarized or non-polarized). Many efforts have been made during the last decade
      to characterize the molecular mechanisms driving lineage divergence.
      METHODOLOGY/PRINCIPAL FINDINGS: In order to evaluate the importance of cell
      polarity in the determination of cell fate we have disturbed the activity of the
      apical complex aPKC/PAR6 using siRNA to down-regulate aPKClambda expression. Here
      we show that depletion of aPKClambda results in an absence of tight junctions and
      in severe polarity defects at the 16-cell stage. Importantly, we found that, in
      absence of aPKClambda, cell fate depends on the cellular context: depletion of
      aPKClambda in all cells results in a strong reduction of inner cells at the 16
      cell stage, while inhibition of aPKClambda in only half of the embryo biases the
      progeny of aPKClambda defective blastomeres towards the inner cell mass. Finally,
      our study points to a role of cell shape in controlling cell position and thus
      lineage allocation. CONCLUSION: Our data show that aPKClambda is dispensable for
      the establishment of polarity at the 8-cell stage but is essential for the
      stabilization of cell polarity at the 16-cell stage and for cell positioning.
      Moreover, this study reveals that in addition to positional information and
      asymmetric cell divisions, cell shape plays an important role for the control of
      lineage divergence during mouse preimplantation development. Cell shape is able
      to influence both the type of division (symmetric or asymmetric) and the position
      of the blastomeres within the embryo.

PMID- 19768118
TI  - Progressive wound necrosis associated with postoperative thrombocytosis in
      mastectomy and immediate breast reconstruction surgery: report of a case.
AB  - A 37-year-old who underwent splenectomy for motor vehicle accident-related
      injuries was diagnosed with stage IIA carcinoma of left breast 12 years later.
      She underwent bilateral mastectomy and bilateral immediate unipedicle TRAM flap
      reconstruction. Her preoperative platelet counts ranged from 332 to 424 K/cmm.
      Intraoperative fluorescein confirmed mastectomy flap viability. On postoperative
      day 1, platelet count was 374 K/cmm and all suture lines appeared benign. The
      patient was discharged 3 days later with healthy appearing tram flaps and slight
      epidermolysis in the abdominal region. Over the next 2 weeks, both the mastectomy
      flaps and the abdominal region underwent progressive necrosis as the platelet
      count increased to 1390 K/cmm. Aspirin therapy was instituted at this time. The
      TRAM flaps remained completely viable. Eighteen days later, the patient required
      wound debridement with secondary closure of the breast wounds. Platelet count
      peaked at 1689 K/cmm 2 days later (postoperative day 38). The wounds deteriorated
      again and were managed conservatively. Two months after mastectomy, the first
      area of spontaneous healing was documented (platelet count 758 K/cmm).
      Ultimately, wounds healed as platelet count reached its preoperative baseline. We
      hypothesize that an abnormal secondary thrombocytosis at subdermal plexus level
      caused problematic healing in this patient's mastectomy and abdominal flaps.

PMID- 19768117
TI  - Nitric oxide induces cell death by regulating anti-apoptotic BCL-2 family
      members.
AB  - Nitric oxide (NO) activates the intrinsic apoptotic pathway to induce cell death.
      However, the mechanism by which this pathway is activated in cells exposed to NO
      is not known. Here we report that BAX and BAK are activated by NO and that
      cytochrome c is released from the mitochondria. Cells deficient in Bax and Bak or
      Caspase-9 are completely protected from NO-induced cell death. The individual
      loss of the BH3-only proteins, Bim, Bid, Puma, Bad or Noxa, or Bid knockdown in
      Bim(-/-)/Puma(-/-) MEFs, does not prevent NO-induced cell death. Our data show
      that the anti-apoptotic protein MCL-1 undergoes ASK1-JNK1 mediated degradation
      upon exposure to NO, and that cells deficient in either Ask1 or Jnk1 are
      protected against NO-induced cell death. NO can inhibit the mitochondrial
      electron transport chain resulting in an increase in superoxide generation and
      peroxynitrite formation. However, scavengers of ROS or peroxynitrite do not
      prevent NO-induced cell death. Collectively, these data indicate that NO degrades
      MCL-1 through the ASK1-JNK1 axis to induce BAX/BAK-dependent cell death.

PMID- 19768120
TI  - Print awareness of adult illiterates: a comparison with young pre-readers and low
      educated adult readers.
AB  - In this study the print awareness of 25 unschooled adult illiterates in the
      Netherlands was compared with that of 24 pre-reading children and of 23 low
      educated literate adults with approximately four years of primary schooling. The
      illiterates were interviewed about their experiences with writing and all
      participants completed six assessments of print awareness in the language they
      preferred (first or second language). The outcomes revealed that the three groups
      did not differ in distinguishing conventional written signs from other visual
      signs, that both groups of non-readers differed significantly from low educated
      readers but not from each other in knowledge of logos, inscriptions and knowledge
      of the written register, while the adult illiterates performed significantly
      better than the children on grapheme knowledge. Adult illiterates in literate
      societies seem to be well informed about the uses and functions of written
      language and about what writing looks like, but like young children they are not
      good at reading environmental print out of context and in explaining what exactly
      is represented in writing. The variation in reactions within the group of
      illiterate adults could be related to existing models of emergent literacy.
      Implications for adult literacy education are discussed.

PMID- 19768119
TI  - Transcriptional profiling of Bacillus anthracis Sterne (34F2) during iron
      starvation.
AB  - Lack of available iron is one of many environmental challenges that a bacterium
      encounters during infection and adaptation to iron starvation is important for
      the pathogen to efficiently replicate within the host. Here we define the
      transcriptional response of B. anthracis Sterne (34F(2)) to iron depleted
      conditions. Genome-wide transcript analysis showed that B. anthracis undergoes
      considerable changes in gene expression during growth in iron-depleted media,
      including the regulation of known and candidate virulence factors. Two genes
      encoding putative internalin proteins were chosen for further study. Deletion of
      either gene (GBAA0552 or GBAA1340) resulted in attenuation in a murine model of
      infection. This attenuation was amplified in a double mutant strain. These data
      define the transcriptional changes induced during growth in low iron conditions
      and illustrate the potential of this dataset in the identification of putative
      virulence determinants for future study.

PMID- 19768121
TI  - Aggregation pheromone compounds of the black larder beetle Dermestes
      haemorrhoidalis Kuster (Coleoptera: Dermestidae).
AB  - Gas chromatography with simultaneous flame ionisation and electroantennographic
      detection (GC-EAD) and gas chromatography with mass spectrometry analysis (GC-MS)
      of abdominal extracts of adult male Dermestes haemorrhoidalis Kuster (Coleoptera:
      Dermestidae) revealed the presence of electrophysiologically and behaviourally
      active compounds to its conspecific males and females. Isopropyl dodecanoate (3),
      isopropyl (Z)-9-tetradecenoate (5), isopropyl tetradecanoate (6), isopropyl (Z)-9
      hexadecenoate (7) and isopropyl hexadecanoate (8) were detected in male abdominal
      extracts only. Analysis of collected male headspace volatiles revealed the
      presence of six EAD-active compounds (3), (5), (6) and isopropyl tridecanoate (4)
      plus two unidentified compounds (1) and (9). Synthetic compounds (3), (4), (5),
      (6) and (7) showed EAD activity with antennae of both sexes in contrast to
      synthetic (8) which showed EAD activity with female antennae only. Male and
      female antennae of D.haemorrhoidalis reacted with high receptor potentials to
      isopropyl (Z)-9-dodecenoate (2), although this compound itself was detected in
      neither male nor female abdominal extracts or headspace volatiles. Petri dish
      bioassays indicated that male abdominal extracts and compounds (2), (3), (5) and
      (6) aroused and attracted conspecific male and female beetles significantly (P <
      0.05) compared to female extracts. These results suggested the presence of a male
      produced aggregation pheromone in D. haemorrhoidalis. Field assays with any of
      the described compounds, however, did not result in attraction of this beetle in
      significant numbers.

PMID- 19768122
TI  - Latino Parents' and Adolescents' Perceptions of the Needs and Issues of
      Adolescents in Their Community.
AB  - Data from The Community Needs Assessment Survey were examined to understand the
      issues parents and adolescents felt were most important to address for the
      adolescents in their community. The sample of 1,784 Latino respondents consisted
      of 892 parent/adolescent dyads. Factor analyses found parents and adolescents
      identified and prioritized the same six factors: education and career planning,
      abuse and victimization, adolescent behavior problems, adolescent sexuality,
      socioeconomic stressors, and relationships. However, parent ratings for all
      factors were higher, indicating a higher level of concern. The article analyzes
      differences by age/generation (parents versus adolescents), by immigrant versus
      native status, and by type of dyad based on the latter (i.e., US born
      adolescent/US born parent, US born adolescent/immigrant parent, immigrant
      adolescent/immigrant parent). The authors discuss the complex interaction of
      these factors and the implications for practice and research.

PMID- 19768123
TI  - A Theoretical Solution to MAP-EM Partial Volume Segmentation of Medical Images.
AB  - Voxels near tissue borders in medical images contain useful clinical information,
      but are subject to severe partial volume (PV) effect, which is a major cause of
      imprecision in quantitative volumetric and texture analysis. When modeling each
      tissue type as a conditionally independent Gaussian distribution, the tissue
      mixture fractions in each voxel via the modeled unobservable random processes of
      the underlying tissue types can be estimated by maximum a posteriori expectation
      maximization (MAP-EM) algorithm in an iterative manner. This paper presents,
      based on the assumption that PV effect could be fully described by a tissue
      mixture model, a theoretical solution to the MAP-EM segmentation algorithm, as
      opposed to our previous approximation which simplified the posteriori cost
      function as a quadratic term. It was found out that the theoretically-derived
      solution existed in a set of high-order non-linear equations. Despite of the
      induced computational complexity when seeking for optimum numerical solutions to
      non-linear equations, potential gains in robustness, consistency and quantitative
      precision were noticed. Results from both synthetic digital phantoms and real
      patient bladder magnetic resonance images were presented, demonstrating the
      accuracy and efficiency of the presented theoretical MAP-EM solution.

PMID- 19768124
TI  - Solid State NMR Studies of Molecular Recognition at Protein-Mineral Interfaces.

PMID- 19768125
TI  - Tracing 'driver' versus 'modulator' information flow throughout large-scale, task
      related neural circuitry.
AB  - PRIMARY OBJECTIVE: To determine the relative uses of neural action potential
      ('spike') data versus local field potentials (LFPs) for modeling information flow
      through complex brain networks.  HYPOTHESIS: The common use of LFP data, which
      are continuous and therefore more mathematically suited for spectral information
      flow modeling techniques such as Granger causality analysis, can lead to spurious
      inferences about whether a given brain area 'drives' the spiking in a downstream
      area.  EXPERIMENT: We recorded spikes and LFPs from the forelimb motor cortex
      (M1) and the magnocellular red nucleus (mRN), which receives axon collaterals
      from M1 projection cells onto its distal dendrites, but not onto its perisomatic
      regions, as rats performed a skilled reaching task.  RESULTS AND IMPLICATIONS: As
      predicted, Granger causality analysis on the LFPs-which are mainly composed of
      vector-summed dendritic currents-produced results that if conventionally
      interpreted would suggest that the M1 cells drove spike firing in the mRN,
      whereas analyses of spiking in the two recorded regions revealed no significant
      correlations. These results suggest that mathematical models of information flow
      should treat the sampled dendritic activity as more likely to reflect intrinsic
      dendritic and input-related processing in neural networks, whereas spikes are
      more likely to provide information about the output of neural network processing.

PMID- 19768126
TI  - Biological assemblies provide novel templates for the synthesis of hierarchical
      structures and facilitate cell adhesion.
AB  - Mechanical mismatch and the lack of interactions between implants and the natural
      tissue environment are the major drawbacks in bone tissue engineering.
      Biomaterials mimicking the self-assembly process and the composition of the bone
      matrix should provide new route for fabricating biomaterials possessing novel
      osteoconductive and osteoinductive properties for bone repair. In the present
      study, we employ bio-inspired strategies to design de novo self-assembled
      chimeric protein hydrogels comprising leucine zipper motifs flanked by dentin
      matrix protein 1 domain, which was characterized as a mineralization nucleator.
      Results showed that this chimeric protein could function as a hydroxyapatite
      nucleator in pseudo-physiological buffer with the formation of highly oriented
      apatites similar to biogenic bone mineral. It could also function as an inductive
      substrate for osteoblast adhesion, promote cell surface integrin presentation and
      clustering, and modulate the formation of focal contacts. Such biomimetic "bottom
      up" construction with dual osteoconductive and osteoinductive properties should
      open new avenues for bone tissue engineering.Mechanical mismatch and the lack of
      interactions between implants and the natural tissue environment are the major
      drawbacks in bone tissue engineering. Biomaterials mimicking the self-assembly
      process and the composition of the bone matrix should provide new route for
      fabricating biomaterials possessing novel osteoconductive and osteoinductive
      properties for bone repair. In the present study, we employ bio-inspired
      strategies to design de novo self-assembled chimeric protein hydrogels comprising
      leucine zipper motifs flanked by dentin matrix protein 1 domain, which was
      characterized as a mineralization nucleator. Results showed that this chimeric
      protein could function as a hydroxyapatite nucleator in pseudo-physiological
      buffer with the formation of highly oriented apatites similar to biogenic bone
      mineral. It could also function as an inductive substrate for osteoblast
      adhesion, promote cell surface integrin presentation and clustering, and modulate
      the formation of focal contacts. Such biomimetic "bottom-up" construction with
      dual osteoconductive and osteoinductive properties should open new avenues for
      bone tissue engineering.

PMID- 19768127
TI  - Calculation of adsorption free energy for solute-surface interactions using
      biased replica-exchange molecular dynamics.
AB  - The adsorption behavior of a biomolecule, such as a peptide or protein, to a
      functionalized surface is of fundamental importance for a broad range of
      applications in biotechnology. The adsorption free energy for these types of
      interactions can be determined from a molecular dynamics simulation using the
      partitioning between adsorbed and nonadsorbed states, provided that sufficient
      sampling of both states is obtained. However, if interactions between the solute
      and the surface are strong, the solute will tend to be trapped near the surface
      during the simulation, thus preventing the adsorption free energy from being
      calculated by this method. This situation occurs even when using an advanced
      sampling algorithm such as replica-exchange molecular dynamics (REMD). In this
      paper, the authors demonstrate the fundamental basis of this problem using a
      model system consisting of one sodium ion (Na(+)) as the solute positioned over a
      surface functionalized with one negatively charged group (COO(-)) in explicit
      water. With this simple system, the authors show that sufficient sampling in the
      coordinate normal to the surface cannot be obtained by conventional REMD alone.
      The authors then present a method to overcome this problem through the use of an
      adaptive windowed-umbrella sampling technique to develop a biased-energy function
      that is combined with REMD. This approach provides an effective method for the
      calculation of adsorption free energy for solute-surface interactions.

PMID- 19768128
TI  - Microscope detection options for colorless protein crystals grown in lipidic
      cubic phases.
AB  - The use of lipidic cubic phases as crystal nucleation and growth matrices is
      becoming popular and has yielded crystals of soluble and membrane proteins. So
      far, all of the membrane proteins crystallized by this method have been colored.
      This feature has facilitated the detection of the often encountered microcrystals
      in initial screening rounds. Indeed, small colorless protein crystals have poor
      optical contrast as a result of the small differences in refractive index of the
      protein crystal and the surrounding lipidic cubic phase. While a perfect
      preparation of a lipidic cubic phase is transparent and optically isotropic, in a
      crystallization setup it frequently disguises crystals due to cracks, inclusions,
      surface distortions and phase boundaries. Here, several specialized microscopic
      techniques and illumination conditions are compared and it is found that
      sufficient contrast is generated by cross polarization microscopy and by Hoffman
      modulation contrast microscopy for the detection of colorless protein crystals.

PMID- 19768129
TI  - Muller cell activation, proliferation and migration following laser injury.
AB  - PURPOSE: Muller cells are well known for their critical role in normal retinal
      structure and function, but their reaction to retinal injury and subsequent role
      in retinal remodeling is less well characterized. In this study we used a mouse
      model of retinal laser photocoagulation to examine injury-induced Muller glial
      reaction, and determine how this reaction was related to injury-induced retinal
      regeneration and cellular repopulation. METHODS: Experiments were performed on 3
      4-week-old C57BL/6 mice. Retinal laser photocoagulation was used to induce small,
      circumscribed injuries; these were principally confined to the outer nuclear
      layer, and surrounded by apparently healthy retinal tissue. Western blotting and
      immunohistochemical analyses were used to determine the level and location of
      protein expression. Live cell imaging of green fluorescent protein (GFP)-infected
      Muller cells (AAV-GFAP-GFP) were used to identify the rate and location of
      retinal Muller cell nuclear migration. RESULTS: Upon injury, Muller cells
      directly at the burn site become reactive, as evidenced by increased expression
      of the intermediate filament proteins glial fibrillary acidic protein (GFAP) and
      nestin. These reactive cells re-enter the cell cycle as shown by expression of
      the markers Cyclin D1 and D3, and their nuclei begin to migrate toward the injury
      site at a rate of approximately 12 microm/hr. However, unlike other reports,
      evidence for Muller cell transdifferentiation was not identified in this model.
      CONCLUSIONS: Retinal laser photocoagulation is capable of stimulating a
      significant glial reaction, marked by activation of cell cycle progression and
      retinal reorganization, but is not capable of stimulating cellular
      transdifferentiation or neurogenesis.

PMID- 19768130
TI  - Inhibition of choroidal neovascularization by topical application of angiogenesis
      inhibitor vasostatin.
AB  - PURPOSE: Choroidal neovascularization (CNV) is the leading cause of blindness in
      patients with age-related macular degeneration (AMD). This study evaluated the
      inhibitory effect of vasostatin (VS), an endogenous angiogenesis inhibitor, on
      CNV. METHODS: Anti-angiogenic activity of VS was evaluated in vitro by migration
      and tube formation assays in human umbilical vein endothelial cells (HUVECs). CNV
      lesions were induced in Brown Norway rats by fundus argon laser photocoagulation.
      Beginning one day after CNV induction, rats were treated with eye drops
      containing 1 microg/ml VS in PBS buffer for three times daily for 20 days. The
      extent of CNV was examined by flat mount analysis on day 24 or by fundus
      fluorescein angiography (FAG) on days 21, 28, 35, and 42, respectively. CNV
      lesions and choroidal vascularity were evaluated by histological analysis. The
      spatial distribution of topically applied VS in rat eyes was evaluated by
      immunoblot analysis. RESULTS: VS inhibited migration and tube formation in
      HUVECs. Flat mount analysis revealed that, after laser-induced photocoagulation,
      topical VS application for 20 days significantly reduced CNV lesions. Moreover,
      serial FAG analysis indicated that a 20 day VS treatment significantly reduced
      CNV lesions on all subsequent days. Histological analysis revealed attenuated
      lesions, intact Bruch's membrane, and reduced choroidal vascularity in VS-treated
      eyes. Finally immunoblot analysis reveled VS expression in choroids. CONCLUSIONS:
      Topical VS application suppresses the progression of laser-induced CNV via
      angiogenesis inhibition and may constitute a therapeutic alternative for
      excessive neovascularization occurring with ocular diseases.

PMID- 19768131
TI  - Challenges Facing Contemporary Associative Approaches to Acquired Behavior.
AB  - Despite the considerable success of contemporary associative models of learning
      in stimulating new behavioral research and modest success in providing direction
      to both neuroscience and psychotherapy, these models are confronted with at least
      three challenges. The first challenge is to the assumption that animals encode
      only one or a few summary statistics to capture what has been experienced over
      many training trials. This assumption is contrary to overwhelming evidence that
      the brain retains episodic information. The second challenge is that the learning
      performance distinction has been largely ignored. Most models erroneously assume
      that behavior is a nearly perfect reflection of what has been encoded. The third
      challenge is to account for interactions between stimuli that have been presented
      separately (e.g., stimulus interference) as well as between stimuli that have
      been presented together (e.g., stimulus competition).

PMID- 19768132
TI  - Innateness, Learning, and Rationality.

PMID- 19768133
TI  - Aurantimonas manganoxydans, sp. nov. and Aurantimonas litoralis, sp. nov.: Mn(II)
      oxidizing representatives of a globally distributed clade of alpha-Proteobacteria
      from the order Rhizobiales.
AB  - Several closely related Mn(II)-oxidizing alpha-Proteobacteria were isolated from
      very different marine environments: strain SI85-9A1 from the oxic/anoxic
      interface of a stratified Canadian fjord, strain HTCC 2156 from the surface
      waters off the Oregon coast, and strain AE01 from the dorsal surface of a
      hydrothermal vent tubeworm. 16S rRNA analysis reveals that these isolates are
      part of a tight phylogenetic cluster with previously characterized members of the
      genus Aurantimonas. Other organisms within this clade have been isolated from
      disparate environments such as surface waters of the Arctic and Mediterranean
      seas, a deep-sea hydrothermal plume, and a Caribbean coral. Further analysis of
      all these strains revealed that many of them are capable of oxidizing dissolved
      Mn(II) and producing particulate Mn(III/IV) oxides. Strains SI85-9A1 and HTCC
      2156 were characterized further. Despite sharing nearly identical 16S rRNA gene
      sequences with the previously described Aurantimonas coralicida, whole genome DNA
      DNA hybridization indicated that their overall genomic similarity is low.
      Polyphasic phenotype characterization further supported distinguishing
      characteristics among these bacteria. Thus SI85-9A1 and HTCC 2156 are described
      as two new species within the family 'Aurantimionadaceae': Aurantimonas
      manganoxydans sp. nov. and Aurantimonas litoralis sp. nov. This clade of bacteria
      is widely distributed around the globe and may be important contributors to Mn
      cycling in many environments. Our results highlight the difficulty in utilizing
      16S rRNA-based approaches to investigate the microbial ecology of Mn(II)
      oxidation.

PMID- 19768135
TI  - Sad Kids, Sad Media? Applying Mood Management Theory to Depressed Adolescents'
      Use of Media.
AB  - Mood management studies typically have found that adults will select media that
      enhance positive moods and reduce negative moods. In this study, adolescents
      diagnosed with major depressive disorder and control adolescents without
      psychiatric disorders were called on customized cell phones up to 4 times a day
      and asked about their current mood state and media use for five extended weekends
      across an 8-week period. Mood effects on subsequent media use, mood during media
      consumption, and media effects on subsequent mood were examined. Results
      indicated that adolescents who consumed fun media tended to do so in a way that
      sustained, rather than enhanced their prior positive mood levels during and after
      consumption-if they turned to media. Adolescents in more negative moods did not
      often use media to improve their moods. When they did, boys were more likely than
      girls to use media that ultimately reduced negative mood levels. Findings are
      discussed in light of the literature on mood management, adolescence, and
      depression.

PMID- 19768134
TI  - Diversity of influenza viruses in swine and the emergence of a novel human
      pandemic influenza A (H1N1).
AB  - The novel H1N1 influenza virus that emerged in humans in Mexico in early 2009 and
      transmitted efficiently in the human population with global spread has been
      declared a pandemic strain. Here we review influenza infections in swine since
      1918 and the introduction of different avian and human influenza virus genes into
      swine influenza viruses of North America and Eurasia. These introductions often
      result in viruses of increased fitness for pigs that occasionally transmit to
      humans. The novel virus affecting humans is derived from a North American swine
      influenza virus that has acquired two gene segments [Neuraminidase (NA) and
      Matrix (M)] from the European swine lineages. This reassortant appears to have
      increased fitness in humans. The potential for increased virulence in humans and
      of further reassortment between the novel H1N1 influenza virus and oseltamivir
      resistant seasonal H1N1 or with highly pathogenic H5N1 influenza stresses the
      need for urgent pandemic planning.

PMID- 19768138
TI  - Violated Wishes About Division of Childcare Labor Predict Early Coparenting
      Process During Stressful and Nonstressful Family Evaluations.
AB  - Prior research has indicated that expectant parents overestimate the extent to
      which fathers will take part in the "work" of parenting, with mothers often
      becoming disenchanted when these expectations are violated following the baby's
      arrival. In this study, we examine the role of violated wishes concerning
      childcare involvement in accounting for variability in maternal and paternal
      marital satisfaction, and in early coparenting behavior as assessed during family
      interaction sessions. The results indicate possible negative effects of violated
      wishes on the enacted family process and confirm previous findings regarding the
      effects of marital satisfaction. In addition, we uncovered differences in the way
      that violated maternal wishes are related to coparenting during playful and
      mildly stressful family interactions.

PMID- 19768137
TI  - Receptor interactions by polybrominated diphenyl ethers versus polychlorinated
      biphenyls: a theoretical Structure-activity assessment.
AB  - The extensive body of literature regarding the interaction of polychlorinated
      biphenyls (PCBs) with transcription factors (receptors) has great value to
      understand similarities and distinctions and in formulating hypotheses regarding
      the activity of polybrominated diphenyl ethers (PBDEs) toward those same
      receptors. Our goal is to present the most comprehensive overview of PBDE effects
      on AhR, CAR, PXR, ER, AR, PR, DHT, TH, T3, T4 and IGF, as well as hypothetical
      biological activities of PPAR, RyR, GR and GABA. Aside the influence of the
      conformation of the ligand, we discuss its constitution influencing the binding
      affinity: size and polarizability, hydrophilicity, Gibbs free energy of
      solvation, inductive and mesomeric effects. We evaluate the techniques to
      determine the biologically relevant conformation of these halogenated
      hydrocarbons, including computation methods, X-ray and microwave spectroscopy. A
      novel fluoro-tagged ligand approach holds promise as tools for illuminating the
      steric and electronic effects in ligand-receptor interaction. Based on our
      assessment, we predict that PBDEs do not exhibit AhR activity themselves, but
      impurities are responsible for these effects.

PMID- 19768136
TI  - In Vivo Cellular Imaging for Translational Medical Research.
AB  - Personalized treatment using stem, modified or genetically engineered, cells is
      becoming a reality in the field of medicine, in which allogenic or autologous
      cells can be used for treatment and possibly for early diagnosis of diseases.
      Hematopoietic, stromal and organ specific stem cells are under evaluation for
      cell-based therapies for cardiac, neurological, autoimmune and other disorders.
      Cytotoxic or genetically altered T-cells are under clinical trial for the
      treatment of hematopoietic or other malignant diseases. Before using stem cells
      in clinical trials, translational research in experimental animal models are
      essential, with a critical emphasis on developing noninvasive methods for
      tracking the temporal and spatial homing of these cells to target tissues.
      Moreover, it is necessary to determine the transplanted cell's engraftment
      efficiency and functional capability. Various in vivo imaging modalities are in
      use to track the movement and incorporation of administered cells. Tagging cells
      with reporter genes, fluorescent dyes or different contrast agents transforms
      them into cellular probes or imaging agents. Recent reports have shown that
      magnetically labeled cells can be used as cellular magnetic resonance imaging
      (MRI) probes, demonstrating the cell trafficking to target tissues. In this
      review, we will discuss the methods to transform cells into probes for in vivo
      imaging, along with their advantages and disadvantages as well as the future
      clinical applicability of cellular imaging method and corresponding imaging
      modality.

PMID- 19768140
TI  - Phenotypic Switching in Fungi.
AB  - Over the past three decades new fungal diseases have emerged that now constitute
      a major threat, especially for patients with chronic diseases and/or underlying
      immune defi ciencies. Despite the epidemiologic data, the emergence of stable
      drug-resistant or hyper-virulent fungal strains in human disease has not been
      demonstrated as seen in emerging viral and bacterial infections. Fungi are
      eukaryotic microbes that capitalize on a sophisticated built-in ability to
      generate phenotypic variability. This successful strategy allows them to undergo
      rapid adaptation in response to environmental challenges, such as individual body
      locations that may exhibit drastic differences in temperature and pH. Rapid
      microevolution can also confer drug resistance and protect them from the host's
      immune response. This review explores phenotypic switching in pathogenic fungi,
      including Candida spp and Cryptococcus spp, and how phenotypic switching
      contributes to the pathogenesis of fungal diseases.

PMID- 19768139
TI  - Glutamatergic Synaptic Dysfunction and Obsessive-Compulsive Disorder.
AB  - Obsessive-compulsive disorder (OCD) is a debilitating neuropsychiatric condition
      estimated to afflict 1-3% of the world population. The estimated financial impact
      in the treatment and management of OCD is in the billions of dollars annually in
      the US alone. At present there is a marked lack of evidence on the specific
      causes of OCD. Current hypotheses largely focus on the serotonin (5-HT) system on
      the basis of the effectiveness of selective serotonin reuptake inhibitors (SSRIs)
      in alleviating symptoms of patients with OCD, yet a considerable fraction of
      patients are non-responsive or minimally responsive to these agents. Despite this
      fact, SSRIs have remained the primary pharmacological treatment avenue for OCD.
      In recent years, multiple lines of evidence have implicated glutamatergic
      synaptic dysfunction within the cortico-striatal-thalamo-cortical (CSTC) brain
      circuit in the etiology of OCD and related disorders, thereby prompting
      intensified effort in the development and evaluation of agents that modulate
      glutamatergic neurotransmission for the treatment of OCD. With this in mind, here
      we review the following topics with respect to synaptic dysfunction and the
      neural circuitry underlying OCD: (1) evidence supporting the critical involvement
      of the CSTC circuit, (2) genetic studies supporting the involvement of
      glutamatergic dysfunction, (3) insights from genetic animal models of OCD, and
      (4) preliminary findings with glutamatergic neurotransmission-modulating agents
      in the treatment of OCD. Given the putative mechanistic overlap between OCD and
      the broader OC-spectrum of disorders, unraveling the synaptic basis of OCD has
      potential to translate into more effective treatments for an array of poorly
      understood human disorders.

PMID- 19768142
TI  - Comparative performances of staging systems for early hepatocellular carcinoma.
AB  - BACKGROUND: Several staging systems for patients with hepatocellular carcinoma
      (HCC) have been proposed, but studies of their prognostic accuracy have yielded
      conflicting conclusions. Stratifying patients with early HCC is of particular
      interest because these patients may derive the greatest benefit from
      intervention, yet no studies have evaluated the comparative performances of
      staging systems in patients with early HCC. METHODS: A retrospective cohort study
      was performed using data on 379 patients who underwent liver resection or liver
      transplantation for HCC at six major hepatobiliary centres in the USA and Europe.
      The staging systems evaluated were: the Okuda staging system, the International
      Hepato-Pancreato-Biliary Association (IHPBA) staging system, the Cancer of the
      Liver Italian Programme (CLIP) score, the Barcelona Clinic Liver Cancer (BCLC)
      staging system, the Japanese Integrated Staging (JIS) score and the American
      Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) staging
      system, 6th edition. A recently proposed early HCC prognostic score was also
      evaluated. The discriminative abilities of the staging systems were evaluated
      using Cox proportional hazards models and the bootstrap-corrected concordance
      index (c). RESULTS: Overall survival of the cohort was 74% at 3 years and 52% at
      5 years, with a median survival of 62 months. Most systems demonstrated poor
      discriminatory ability (P > 0.05 on Cox proportional hazards analysis, c
      approximately 0.5). However, the AJCC/UICC system clearly stratified patients (P
      < 0.001, c = 0.59), albeit only into two groups. The early HCC prognostic score
      also clearly stratified patients (P < 0.001, c = 0.60) and identified three
      distinct prognostic groups. DISCUSSION: The early HCC prognostic score is
      superior to the AJCC/UICC staging system (6th edition) for predicting the
      survival of patients with early HCC after liver resection or liver
      transplantation. Other major HCC staging systems perform poorly in patients with
      early HCC.

PMID- 19768141
TI  - Anti-inflammatory effects of the Nigella sativa seed extract, thymoquinone, in
      pancreatic cancer cells.
AB  - BACKGROUND: Both hereditary and sporadic forms of chronic pancreatitis are
      associated with an increased risk of developing pancreatic ductal adenocarcinoma
      (PDA). Inflammation has been identified as a significant factor in the
      development of solid tumour malignancies. We have recently shown that
      thymoquinone (Tq), the major constituent of Nigella sativa oil extract, induced
      apoptosis and inhibited proliferation in PDA cells. Tq also increased p21 WAF1
      expression, inhibited histone deacetylase (HDAC) activity, and induced histone
      hyperacetylation. HDAC inhibitors have been shown to ameliorate inflammation
      associated cancer. In this study, we evaluated the anti-inflammatory potential of
      Tq in PDA cells in comparison with that of a specific HDAC inhibitor,
      trichostatin A (TSA). METHODS: PDA cells were treated with or without Tq (25-75
      microM), with or without pre-treatment of tumour necrosis factor (TNF)-alpha (25
      ng/ml). The effect of Tq on the expression of different proinflammatory cytokines
      and chemokines was analysed by real-time polymerase chain reaction (PCR).
      Luciferase-labelled promoter studies evaluated the effect of Tq on the
      transcription of monocyte chemoattractant protein-1 (MCP-1) and nuclear factor
      kappaB (NF-kappaB). The effect of Tq on the constitutive and TNF-alpha-induced
      activation and nuclear translocation of NF-kappaB was examined by ELISA and
      immunohistochemistry. RESULTS: Tq dose- and time-dependently significantly
      reduced PDA cell synthesis of MCP-1, TNF-alpha, interleukin (IL)-1beta and Cox-2.
      At 24 h, Tq almost completely abolished the expression of these cytokines,
      whereas TSA had a less dramatic effect. Tq, but not TSA, significantly and dose
      dependently reduced the intrinsic activity of the MCP-1 promoter. Tq also
      inhibited the constitutive and TNF-alpha-mediated activation of NF-kappaB in PDA
      cells and reduced the transport of NF-kappaB from the cytosol to the nucleus.
      CONCLUSIONS: Our data demonstrate previously undescribed anti-inflammatory
      activities of Tq in PDA cells, which are paralleled by inhibition of NF-kappaB.
      Tq as a novel inhibitor of proinflammatory pathways provides a promising strategy
      that combines anti-inflammatory and proapoptotic modes of action.

PMID- 19768143
TI  - National hospital volume in acute pancreatitis: analysis of the Nationwide
      Inpatient Sample 1998-2006.
AB  - BACKGROUND: The optimal management of acute pancreatitis remains controversial
      and current treatment protocols vary in degrees of medical and surgical
      management. Our group has previously shown in population-based studies that high
      volume (HV) hospitals have lower rates of in-hospital mortality after
      pancreatectomy. We sought to examine if a similar mortality benefit exists for
      patients admitted with acute pancreatitis. METHODS: Using the Nationwide
      Inpatient Sample (NIS), we examined discharge records for all adult admissions
      during 1998-2006 with a primary diagnosis of acute pancreatitis of any aetiology.
      Unique hospital identifiers were used to divide hospital volumes into equal
      thirds based on the number of admissions for acute pancreatitis per year (lowest
      tertile [low volume, LV] < or = 64 admissions/year; medium tertile [medium
      volume, MV] 65-117 admissions/year; highest tertile [high volume, HV] > or = 118
      admissions/year). Covariates included patient demographics, hospital
      characteristics and patient co-morbidities using the Elixhauser index. Adjusted
      mortality represented the primary outcome measure and adjusted length of stay
      (LOS) and total charges were considered secondary measures. RESULTS: There were
      416,489 primary admissions for acute pancreatitis during the study period. In
      hospital mortality for the cohort amounted to 1.6% (n = 6446). Hospital
      admissions for acute pancreatitis increased over the study period (P < 0.0001).
      High-volume hospitals tended to be large (82%), urban (99%) teaching (59%)
      centres (P < 0.0001), which cared for patients with more co-morbidities (35.9% of
      patients at HV hospitals vs. 29.1% at LV hospitals had at least three co
      morbidities; P < 0.0001). Low-volume centres appeared more likely to perform
      pancreatic procedures than HV hospitals (odds ratio [OR] 1.50, 95% confidence
      interval [CI] 1.32-1.70). Patients at HV hospitals had a lower likelihood of a
      prolonged adjusted LOS compared with those at LV (OR 0.75, 95% CI 0.71-0.79) or
      MV (OR 0.82, 95% CI 0.79-0.85) hospitals. After adjusting for patient and
      hospital factors, there was an in-hospital mortality benefit associated with
      being treated at an HV centre (OR 0.70, 95% CI 0.63-0.77). The decision to
      operate on a given patient did not alter the mortality benefit of the HV
      hospital. CONCLUSIONS: Rates of admissions for acute pancreatitis in the USA are
      increasing. High annual hospital volume of acute pancreatitis cases confers a
      shorter LOS, lower adjusted mortality and a lower likelihood of pancreatic
      procedure for patients admitted with acute pancreatitis. Although HV hospitals
      were less likely than MV or LV centres to perform pancreatic procedures, the role
      of surgery remains unclear. Further studies should examine other possible reasons
      for this mortality benefit, such as the availability of specialists, the quality
      of critical care facilities and the timing of operative intervention.

PMID- 19768144
TI  - Surgical dilemma: liver resection or liver transplantation for hepatocellular
      carcinoma and cirrhosis. Intention-to-treat analysis in patients within and
      outwith Milan criteria.
AB  - BACKGROUND: The optimal role of surgery in the management of hepatocellular
      carcinoma (HCC) is in continuous evolution. OBJECTIVE: The objective of this
      study was to analyse survival rates after liver resection (LR) and orthotopic
      liver transplantation (OLT) for HCC within and outwith Milan criteria in an
      intention-to-treat analysis. METHODS: During 1997-2007, 179 patients with
      cirrhosis and HCC either underwent LR (n= 60) or were listed for OLT (n= 119).
      Patients with incidental HCC after OLT, preoperative macrovascular invasion
      before LR, non-cirrhosis and Child-Pugh class C cirrhosis prior to OLT were
      eliminated, leaving 51 patients primarily treated with LR and 106 patients listed
      for primary OLT (84 of whom were transplanted) to be included in this analysis. A
      total of 66 patients fell outwith Milan criteria (26 LR, 40 OLT) and 91 continued
      to meet Milan criteria (25 LR, 66 OLT). RESULTS: The median length of follow-up
      was 26 months. The mean waiting time for OLT was 7 months. During that time, 21
      patients were removed from the waiting list as a result of tumour progression.
      Probabilities of dropout were 2% and 13% at 6 and 12 months, respectively, for
      patients within Milan criteria, and 34% and 57% at 6 and 12 months, respectively,
      for patients outwith Milan criteria (P < 0.01). Tumour size >3 cm was found to be
      the independent factor associated with dropout (hazard ratio [HR] 6.0).
      Postoperative survival was slightly higher after OLT, but this was not
      statistically significant (64% for OLT vs. 57% for LR). Overall survival from
      time of listing for OLT or LR did not differ between the two groups (P= 0.9); for
      patients within Milan criteria, 1- and 4-year survival rates after LR were 88%
      and 61%, respectively, compared with 92% and 62%, respectively, after OLT (P=
      0.54). For patients outwith Milan criteria, 1- and 4-year survival rates after LR
      were 69% and 54%, respectively, compared with 65% and 40%, respectively, after
      OLT (P= 0.42). Tumour size >3 cm was again found to be an independent factor for
      poor outcome (HR 2.4) in the intention-to-treat analysis. CONCLUSIONS: Survival
      rates for patients with HCC are similar in LR and OLT. Liver resection can
      potentially decrease the dropout rate and serve as a bridge for future salvage
      LT, particularly in patients with tumours >3 cm.

PMID- 19768145
TI  - ACS-NSQIP has the potential to create an HPB-NSQIP option.
AB  - BACKGROUND: The American College of Surgeons National Surgical Quality
      Improvement Program (ACS-NSQIP) was started in 2004. Presently, 58% of the 198
      hospitals participating in ACS-NSQIP are academic or teaching hospitals. In 2008,
      ACS-NSQIP initiated a number of changes and made risk-adjusted data available for
      use by participating hospitals. This analysis explores the ACS-NSQIP database for
      utility in developing hepato-pancreato-biliary (HPB) surgery-specific outcomes
      (HPB-NSQIP). METHODS: The ACS-NSQIP Participant Use File was queried for patient
      demographics and outcomes for 49 HPB operations from 1 January 2005 through 31
      December 2007. The procedures included six hepatic, 16 pancreatic and 23 complex
      biliary operations. Four laparoscopic or open cholecystectomy operations were
      also studied. Risk-adjusted probabilities for morbidity and mortality were
      compared with observed rates for each operation. RESULTS: During this 36-month
      period, data were accumulated on 9723 patients who underwent major HPB surgery,
      as well as on 44,189 who received cholecystectomies. The major HPB operations
      included 2847 hepatic (29%), 5074 pancreatic (52%) and 1802 complex biliary (19%)
      procedures. Patients undergoing hepatic resections were more likely to have
      metastatic disease (42%) and recent chemotherapy (7%), whereas those undergoing
      complex biliary procedures were more likely to have significant weight loss
      (20%), diabetes (13%) and ascites (5%). Morbidity was high for hepatic,
      pancreatic and complex biliary operations (20.1%, 32.4% and 21.2%, respectively),
      whereas mortality was low (2.3%, 2.7% and 2.7%, respectively). Compared with
      laparoscopic cholecystectomy, the open operation was associated with higher rates
      of morbidity (19.2% vs. 6.0%) and mortality (2.5% vs. 0.3%). The ratios between
      observed and expected morbidity and mortality rates were <1.0 for hepatic,
      pancreatic and biliary operations. CONCLUSIONS: These data suggest that HPB
      operations performed at ACS-NSQIP hospitals have acceptable outcomes. However,
      the creation of an HPB-NSQIP has the potential to improve quality, provide risk
      adjusted registries with HPB-specific data and facilitate multi-institutional
      clinical trials.

PMID- 19768146
TI  - Temporal trends in liver transplant centre volume in the USA.
AB  - BACKGROUND: Although prior studies have suggested an inverse association between
      liver transplant centre volume and postoperative patient mortality, more recent
      analyses have failed to confirm this association. To date, all studies of the
      relationship between centre volume and outcomes in liver transplantation have
      been cross-sectional in design. OBJECTIVE: The objective of our study was to
      examine temporal trends in the volume-outcomes relationship for liver
      transplantation. METHODS: We used information obtained from the Scientific
      Registry of Transplant Recipients (SRTR) programme-specific data reports to
      examine the outcomes of adult liver transplant recipients stratified by annual
      centre volume. This relationship between centre volume and patient outcomes was
      assessed over three consecutive time periods from 2000 through 2007. RESULTS: The
      overall 25% increase in adult liver transplant volume in the USA from 2000 to
      2007 appeared to be distributed fairly equally among existing transplant centres.
      In the earliest time period of our analysis, high-volume centres achieved
      superior risk-adjusted 1-year patient outcomes compared with low-volume centres.
      By the third and most recent time period of the analysis, this discrepancy
      between the outcomes of high- and low-volume centres was no longer statistically
      apparent. CONCLUSIONS: The relationship between centre volume and patient
      outcomes for liver transplantation in the USA has become less pronounced over
      time, suggesting that the use of procedure volume as a marker of liver transplant
      centre quality cannot be justified. The performance-based review process
      currently utilized in the USA may have contributed to this diminishing influence
      of centre volume on liver transplant recipient outcomes. This type of review
      process should be considered as a potential alternative to the volume-based
      referral initiatives that have been developed for other non-transplant, complex
      surgical procedures.

PMID- 19768147
TI  - A simplified prognostic system for resected pancreatic neuroendocrine neoplasms.
AB  - BACKGROUND: A number of prognostically relevant clinicopathological variables
      have been proposed for pancreatic neuroendocrine neoplasms. However, a
      standardized prognostication system has yet to be established for patients
      undergoing potentially curative tumour resection. METHODS: We examined a
      prospectively maintained, single-institution database to identify patients who
      underwent potentially curative resection of non-metastatic primary pancreatic
      neuroendocrine neoplasms. Patient, operative and pathological characteristics
      were analysed to identify variables associated with disease-specific and disease
      free survival. RESULTS: Between 1991 and 2007, 43 patients met inclusion
      criteria. After a median follow-up of 68 months, 5-year disease-specific survival
      was 94% and 5-year disease-free survival was 72%. Tumours sized > or = 5 cm and
      vascular invasion were associated with worse disease-specific survival. Tumours
      sized > or = 5 cm, nodal metastases, positive resection margins and perineural
      invasion were associated with worse disease-free survival. A scoring system
      consisting of tumour size > or = 5 cm, histological grade, nodal metastases and
      resection margin positivity (SGNM) permitted stratification of disease-specific
      (P= 0.006) and disease-free (P= 0.0004) survival. This proposed scoring system
      demonstrated excellent discrimination of individual disease-specific and disease
      free survival outcomes as reflected by concordance indices of 0.814 and 0.794,
      respectively. CONCLUSIONS: A simple scoring system utilizing tumour size,
      histological grade, nodal metastases and resection margin status can be used to
      stratify outcomes in patients undergoing resection of primary pancreatic
      neuroendocrine neoplasms.

PMID- 19768148
TI  - Aetiology and outcome of acute liver failure.
AB  - BACKGROUND: Acute liver failure (ALF) is a clinical syndrome characterized by the
      sudden onset of coagulopathy and encephalopathy. The outcome is unpredictable and
      is associated with high morbidity and mortality. We reviewed our experience to
      identify the aetiology and study the outcome of acute liver failure. METHODS: A
      total of 1237 patients who presented with acute liver failure between January
      1992 and May 2008 were included in this retrospective study. Liver
      transplantation was undertaken based on the King's College Hospital criteria.
      Data were obtained from the units prospectively collected database. The following
      parameters were analysed: patient demographics, aetiology, operative
      intervention, overall outcome, 30-day mortality and regrafts. RESULTS: There were
      558 men and 679 women with a mean age of 37 years (range: 8-78 years). The most
      common aetiology was drug-induced liver failure (68.1%), of which 90% was as a
      result of a paracetamol overdose. Other causes include seronegative hepatitis
      (15%), hepatitis B (2.6%), hepatitis A (1.1%), acute Budd-Chiari syndrome (1.5%),
      acute Wilson's disease (0.6%), subacute necrosis(3.2%) and miscellaneous (7.8%).
      Three hundred and twenty-seven patients (26.4%) were listed for liver
      transplantation, of which 263 patients successfully had the procedure (80.4%).
      The current overall survival after transplantation was 70% with a median follow
      up of 57 months. After transplantation for ALF, the 1-year, 5-year and 10-year
      survival were 76.7%, 66% and 47.6%, respectively. The 30-day mortality was 13.7%.
      Out of the 974 patients who were not transplanted, 693 patients are currently
      alive. Among the 281 patients who died without transplantation, 260 died within
      30 days of admission (26.7%). Regrafting was performed in 31 patients (11.8%),
      the most common indication being hepatic artery thrombosis (11 patients).
      CONCLUSION: Paracetamol overdose was the most common cause of acute liver
      failure. Liver transplantation, when performed for acute liver failure, has good
      long-term survival.

PMID- 19768149
TI  - Single nucleotide polymorphism in RECQL and survival in resectable pancreatic
      adenocarcinoma.
AB  - BACKGROUND: RECQL is a DNA helicase involved in DNA mismatch repair. The RECQL
      polymorphism, 3' untranslated region (UTR) A159C, was previously associated with
      overall survival of patients with resectable pancreatic adenocarcinoma treated
      with neoadjuvant chemoradiation. In the present study, we examined RECQL for
      somatic mutations and other polymorphisms and compared these findings with the
      outcome in patients who received adjuvant or neoadjuvant chemoradiation. We
      hypothesized that RECQL (i) would be mutated in cancer, (ii) would have
      polymorphisms linked to the 3'UTR A159C and that either or both events would
      affect function. We also hypothesized that (iii) these changes would be
      associated with survival in both cohorts of patients. MATERIAL AND METHODS: We
      sequenced RECQL's 15 exons and surrounding sequences in paired blood and tumour
      DNA of 39 patients. The 3'UTR A159C genotype was determined in blood DNA samples
      from 176 patients with resectable pancreatic adenocarcinoma treated with adjuvant
      (53) or neoadjuvant (123) chemoradiation. Survival was calculated using the
      Kaplan-Meier method, with log rank comparisons between groups. The relative
      impact of genotype on time to overall survival was performed using the Cox
      proportional hazards model. RESULTS: Somatic mutations were found in UTRs and
      intronic regions but not in exonic coding regions of the RECQL gene. Two single
      nucleotide polymorphisms (SNPs), located in introns 2 and 11, were found to be
      part of the same haplotype block as the RECQL A159C SNP and showed a similar
      association with overall survival. No short-term difference in survival between
      treatment strategies was found. We identified a subgroup of patients responsive
      to neoadjuvant therapy in which the 159 A allele conferred strikingly improved
      long-term survival. DISCUSSION: The RECQL 3'UTR A159C SNP is not linked with
      other functional SNPs within RECQL but may function as a site for regulatory
      molecules. The mechanism of action needs to be clarified further.

PMID- 19768150
TI  - Role of preoperative biliary drainage of liver remnant prior to extended liver
      resection for hilar cholangiocarcinoma.
AB  - BACKGROUND: In patients with hilar cholangiocarcinoma, ipsilateral en bloc
      hepatic resection improves survival but is associated with increased morbidity.
      Preoperative biliary drainage of the future liver remnant (FLR) and contralateral
      portal vein embolization (PVE) may improve perioperative outcome, but their
      routine use is controversial. This study analyses the impact of FLR volume and
      preoperative biliary drainage on postoperative hepatic insufficiency and
      mortality rates. METHODS: Patients who underwent hepatic resection and for whom
      adequate imaging data for FLR calculation were available were identified
      retrospectively. Patient demographic, operative and perioperative data were
      recorded and analysed. The volume of the FLR was calculated based on the total
      liver volume and the volume of the resection that was actually performed using
      semi-automated contouring of the liver on preoperative helical acquired scans. In
      patients subjected to preoperative biliary drainage, the preoperative imaging was
      reviewed to determine if the FLR had been decompressed. Hepatic insufficiency was
      defined as a postoperative rise in bilirubin of 5 mg/dl above the preoperative
      level that persisted for >5 days postoperatively. Operative mortality was defined
      as death related to the operation, whenever it occurred. RESULTS: Sixty patients
      were identified who underwent hepatic resection between 1997 and 2007 and for
      whom imaging data were available for analysis. During this period, preoperative
      biliary drainage of the FLR was used selectively and PVE was used in only one
      patient. The mean age of the patients was 64 +/- 11.6 years and 68% were male.
      The median length of stay was 14 days and the overall morbidity and mortality
      were 53% and 10%, respectively. Preoperative FLR volume was a predictor of
      hepatic insufficiency and death (P= 0.03). A total of 65% of patients had an FLR
      volume > or = 30% (39/60) of the total volume. No patient in this group had
      hepatic insufficiency, but there were two operative deaths (5%), both occurring
      in patients who underwent preoperative biliary drainage. By contrast, in the
      group with FLR < 30% (21/60, 35%), hepatic insufficiency was seen in five
      patients and operative mortality in four patients, and were strongly associated
      with lack of preoperative biliary drainage of the FLR (P = 0.009). Patients with
      an FLR > or = 30% were more likely to have radiographic evidence of ipsilateral
      lobar atrophy and hypertrophy of the FLR (46.2% vs. 9.5% in patients with FLR <
      30%; P = 0.004). CONCLUSIONS: In patients undergoing liver resection for hilar
      cholangiocarcinoma, FLR volume of < 30% of total liver volume is associated with
      increased risk for hepatic insufficiency and death. Preoperative biliary drainage
      of the FLR appears to improve outcome if the predicted volume is < 30%. However,
      in patients with FLR > or = 30%, preoperative biliary drainage does not appear to
      improve perioperative outcome and, as many of these patients have hypertrophy of
      the FLR, PVE is likely to offer little benefit.

PMID- 19768160
TI  - President's address: knowledge, compassion and restless spirit.

PMID- 19768161
TI  - Toward a comprehensive understanding of allergic lung disease.
AB  - Allergic asthma is a respiratory disease induced by exposure to environmental
      agents that elicit allergic inflammation and transient airway obstruction and
      which produce the characteristic symptoms of cough and dyspnea. Prior to the
      advent of experimental models, asthma was believed to be caused primarily by the
      degranulation of mast cells and eosinophils primed by antigen-specific
      immunoglobulin E (IgE). More recent studies in mice have shown that T cells
      primarily mediate antigen-dependent airway obstruction and allergic inflammation
      through secretion of the cytokines interleukin 4 (IL- 4) and IL-13. Our
      additional studies indicate that a major environmental link to asthma may be
      through exposure to environmental proteinases and especially airway infection by
      proteinase-producing organisms such as fungi. Pending verification in humans,
      these findings suggest entirely new therapeutic interventions in asthma that
      include the restricted use of anti-inflammatory therapy and universal application
      of anti-fungal agents.

PMID- 19768162
TI  - The role of circulating mesenchymal progenitor cells, fibrocytes, in promoting
      pulmonary fibrosis.
AB  - The resident fibroblast has been traditionally viewed as the primary cell
      involved in promoting pulmonary fibrosis. However, contemporary findings now
      support the concept of a circulating cell (fibrocyte) that also contributes to
      pulmonary fibrosis. Fibrocytes are bone marrow-derived mesenchymal progenitor
      cells that express a variety of cell surface markers related to leukocytes,
      hematopoietic progenitor cells and fibroblasts. Fibrocytes are unique in that
      they are capable of differentiating into fibroblasts and myofibroblasts, as well
      as adipocytes. In this review, we present data supporting the critical role these
      cells play in the pathogenesis of pulmonary fibrosis.

PMID- 19768163
TI  - Transforming growth factor beta and excess burden of renal disease.
AB  - End-stage renal disease (ESRD) is more frequent in African Americans (blacks)
      compared to whites. Because renal fibrosis is a correlate of progressive renal
      failure and a dominant feature of ESRD, and because transforming growth factor
      beta 1 (TGF-beta1) can induce fibrosis and renal insufficiency, we hypothesized
      that TGF-beta1 hyperexpression is more frequent in blacks compared to whites. We
      measured circulating levels of TGF-beta1 in black and white patients with ESRD,
      hypertension, and in normal patients. We demonstrated that circulating levels of
      TGF-beta1 are higher in black ESRD patients, hypertensive patients, and normal
      control patients compared to their white counterparts. Our preliminary genetic
      analyses suggest that TGF-beta1 DNA polymorphisms are different in blacks and
      whites. Our observations of hyperexpression of TGF-beta1 in blacks suggest a
      mechanism for the increased prevalence of renal failure and hypertensive target
      organ damage in this population.

PMID- 19768164
TI  - HIV and infectious disease care in jails and prisons: breaking down the walls
      with the help of academic medicine.
AB  - Health care within correctional facilities has traditionally been marginalized
      from excellence in academic medicine. The armamentarium of a medical school,
      which includes excellence in research, teaching and clinical care, can be
      successfully applied to the correctional setting both in the United States and
      internationally. At any one time, there are over 2 million people incarcerated in
      the US who are disproportionately poor and from communities of color. Rates of
      human immunodeficiency virus (HIV) and hepatitis C virus infection (HCV) in
      prisons are 5 and 17-28-times higher than in the general population,
      respectively. The correctional setting provides an excellent opportunity to
      screen for and treat sexually transmitted infections (STIs), HIV, HCV, chronic
      hepatitis B virus (HBV) infections and tuberculosis (TB) and to develop effective
      prevention programs.

PMID- 19768166
TI  - Introduction to the symposium on global climate and health.

PMID- 19768165
TI  - My journey to the ants.
AB  - In this paper, I review the strange, unplanned and unexpected journey I have had
      with Solenopsis invicta, the imported fire ant. Through serendipity, good fortune
      and repeated invenomation, I have come to count as collaborators a number of
      entomologists, toxicologists, allergists and immunologists who have guided me on
      this journey to the ants. We now understand the mechanisms for the cutaneous
      reactions experienced by 50% of the exposed population stung per year, as well as
      the immunologic and toxicologic properties of the ants unique venom. Allergen
      immunotherapy to fire ant extracts has been demonstrated to protect patients from
      repeat anaphylaxis. Methods have been developed to prevent and treat massive
      sting attacks on frail elders, including those in residential and medical
      facilities. The potential beneficial effects of venom components are under
      investigation. And yes, the journey and the stings continue.

PMID- 19768167
TI  - "My flying machine was out of order".
AB  - Why did the founders of this organization-which was established in 1884 as the
      American Climatological Association-want to study climatology and respiratory
      diseases? In particular, where did the idea of treating tuberculosis with pure
      air and sunlight come from? How effective was this treatment for a disease that
      in 1880 afflicted a third of the population of Colorado? Why did this Association
      not acknowledge technological advances such as weather forecasting or large
      20(th) century population movements? This paper seeks to answer those questions
      in order to inform the Association's possible study of the effects of global
      climate change on human health, an issue that is arguably comparable to what the
      founders faced. Recent governmental reports suggest that the medical and health
      care communities have not yet become engaged. If the ACCA does not, then who
      will?

PMID- 19768168
TI  - Climate change and human health.
AB  - Climate change science points to an increase in sea surface temperature,
      increases in the severity of extreme weather events, declining air quality, and
      destabilizing natural systems due to increases in greenhouse gas emissions. The
      direct and indirect health results of such a global imbalance include excessive
      heat-related illnesses, vector- and waterborne diseases, increased exposure to
      environmental toxins, exacerbation of cardiovascular and respiratory diseases due
      to declining air quality, and mental health stress among others. Vulnerability to
      these health effects will increase as elderly and urban populations increase and
      are less able to adapt to climate change. In addition, the level of vulnerability
      to certain health impacts will vary by location. As a result, strategies to
      address climate change must include health as a strategic component on a regional
      level. The co-benefits of improving health while addressing climate change will
      improve public health infrastructure today, while mitigating the negative
      consequences of a changing climate for future generations.

PMID- 19768170
TI  - Global climate change and health: developing a research agenda for the NIH.
AB  - Global climate change is receiving worldwide attention because of its anticipated
      impacts on the Earth's physical and biological systems. Through its effects on
      natural and human environments, climate change will likely impact economic
      viability and human health and well-being. The impact of climate change on human
      health is likely to be complex and significant, including effects on cancers,
      cardiovascular and respiratory disease, food-, water-, and vector-borne diseases,
      heat-related illness, mental and social well-being, nutrition, trauma, and
      vulnerable demographic sectors. Most assessments predict that these effects will
      disproportionately affect the poor, the elderly and the young, especially those
      living in Africa and Southeast Asia, where environmental conditions are poor,
      health infrastructure is weak and the burden of disease is great. Enormous
      efforts are underway to plan and finance climate change adaptation programs
      within national governments (including multiple U.S. agencies), United Nations
      organizations and private philanthropies. However, these endeavors are proceeding
      with a relatively poor understanding of the nature and magnitude of probable
      effects of climate change on health. The National Institutes of Health (NIH)
      already funds a portfolio of projects that are indirectly related to the concerns
      posed by global climate change. At the NIH, we have recently established an
      agency-wide planning group to assess the research questions in health and
      medicine that climate change presents, to link this agenda to parallel activities
      across other agencies of the U.S. Government (USG), and to advance a NIH research
      agenda in this area.

PMID- 19768169
TI  - Cholera and climate: a demonstrated relationship.
AB  - Vibrio cholerae, the causative agent of cholera, is naturally present in the
      environment and autochthonous to coastal and estuarine ecosystems. V. cholerae is
      associated with copepods for its survival and multiplication in the natural
      environment. Changes in the density of its reservoir may result in modification
      of the bacterial population size in the environment. In this context, climate
      and/or environmental changes will influence the emergence of cholera in human
      populations. Several human pathogens are naturally occurring in the aquatic
      environment and can pose a threat to public health, including V. cholerae. We
      present results of a project, the goal of which was to improve the understanding
      of environmental factors associated with occurrence and distribution of the
      causative agent of cholera in time and space. The system that was developed
      provides real-time as well as short-term to seasonal forecasts of the likelihood
      of occurrence of V. cholerae in the Chesapeake Bay. The system, and potential
      future improved versions of it, may be useful to public health officials
      concerned with environmental factors influencing human health.

PMID- 19768172
TI  - Introduction of Gordon Wilson Medal recipient Dr. Michael Welsh.

PMID- 19768173
TI  - Development of a porcine model of cystic fibrosis.
AB  - Cystic Fibrosis (CF) is a common autosomal recessive disease that affects
      multiple organs. The lack of an animal model with manifestations like those
      typically found in humans has slowed understanding of its pathogenesis.
      Therefore, because of the similarities between human and swine anatomy,
      biochemistry, physiology, size, and genetics, we chose to develop a porcine model
      of CF. We used homologous recombination in primary cultures of porcine
      fibroblasts to disrupt the CFTR gene and then used those cells as nuclear donors
      for somatic cell nuclear transfer. After crossing heterozygous pigs, we produced
      CFTR-/- pigs. The newborn CFTR null piglets manifested meconium ileus, pancreatic
      destruction, early focal biliary cirrhosis, and gall bladder abnormalities that
      were very similar to those observed in humans with CF. At birth, there were no
      abnormalities in the airway epithelium or submucosal glands and no evidence of
      inflammation, consistent with findings in the newborn human. We hope that this
      porcine model will help elucidate the pathogenesis of CF and thereby lead to the
      development of new mechanism-based therapies.

PMID- 19768174
TI  - Statins and ezetimibe modulate plasma proprotein convertase subtilisin kexin-9
      (PCSK9) levels.
AB  - PCSK9 is a natural inhibitor of the LDL receptor. Gain-of-function mutations may
      cause the familial hypercholesterolemia phenotype, whereas loss-of-function
      variants associate with reduced LDL-C levels and lower coronary risk. Statins up
      regulate PCSK9 in hepatocytes. We developed an assay to measure total PCSK9 in
      human plasma and evaluated the effect of statins and ezetimibe on PCSK9 in vivo
      and in vitro. In 254 normal subjects, the mean plasma PCSK9 was 89 +/- 32 ng/ml.
      PCSK9 levels correlated with plasma cholesterol, LDL-C, triglycerides, fasting
      glucose, age and body mass index. Sequencing PCSK9 from subjects at the extremes
      of plasma distribution revealed new variants. In 200 hypercholesterolemic
      patients, circulating PCSK9 was higher than in controls, increased with
      increasing statin dose, and further increased when ezetimibe was added. However,
      ezetimibe treatment of HepG2 (hepatocytes) and Caco-2 (enterocytes) cells caused
      a slight increase in PCSK9 and NPC1L1 mRNA, but no significant rise in PCSK9
      protein secretion, suggesting that these transformed cells are not ideal model
      cell lines.

PMID- 19768176
TI  - Theodore E. Woodward Award: Coming in out of the rain. Relieving congestion in
      heart failure.
AB  - Heart failure decompensation is dominated by congestive symptoms from elevated
      pulmonary and systemic venous pressures. In dilated heart failure, forward flow
      is optimal at near-normal filling pressures, with minimized mitral regurgitation.
      Tailored therapy to reduce filling pressures improves symptoms acutely. However,
      monitored reduction of filling pressures during hospitalization did not translate
      into improved outcome during the ESCAPE trial. Data recently analyzed from the
      COMPASS trial indicates that 1) ambulatory filling pressures are far higher than
      clinically suspected, 2) filling pressures begin to increase over 3 weeks before
      heart failure events, and 3) events occurring during weight-based management show
      mismatch between changes in weight and changes in filling pressures. Accumulated
      days of high filling pressures increases risk continuously above left-sided
      filling pressures of 15 mmHg. The challenge is to intensify not only acute
      management of heart failure but ambulatory surveillance to allow early
      intervention and reduce re-hospitalization.

PMID- 19768178
TI  - The Barker hypothesis: how pediatricans will diagnose and prevent common adult
      onset diseases.

PMID- 19768177
TI  - Having a change of heart: reversing the suicidal proclivities of cardiac
      myocytes.
AB  - The molecular and cellular basis for cardiac remodeling have been difficult to
      establish. Transcriptional analysis and genetic manipulation of the mouse heart
      have revealed expression of a molecular program for cardiac myocyte suicide under
      conditions of myocardial injury or hemodynamic stress. Interrupting the
      cardiomyocyte suicide program by selective ablation of inducible apoptosis genes
      has proven to be remarkably effective in preventing remodeling and heart failure
      following myocardial infarction. Since these apoptotic genes are similarly
      dysregulated in human heart disease, the stage is set for a new era of
      therapeutics targeting cardiac suicide genes and their products.

PMID- 19768179
TI  - Portraits of an illness.
AB  - Access to patients' inner lives can be expanded and enriched by incorporating the
      arts and humanities into the clinical encounter. A series of self-portraits
      created by an artist undergoing induction chemotherapy for leukemia afforded a
      unique opportunity to concentrate one's gaze upon the patient as a stimulus for
      reflection on suffering and isolation of patients. Poetry and theater were also
      invaluable in expanding the physician's awareness of the shared experience of
      illness. The process highlights the central role of the "New Humanities" in
      modern medicine, where science informs the arts and the arts inform science and
      medicine.

PMID- 19768180
TI  - New medical schools in the United States: forces of change past and present.
AB  - The new millennium has ushered in a growth phase in the number of American
      medical schools. Historically the United States has built schools during bursts
      of activity with relative quiescence in between these periods. We had a twenty
      two year period with no growth in medical school size or number. During that time
      there were significant changes in patient characteristics, student culture,
      financial reimbursement, quality, and manpower needs that have put stress on
      medical schools, hospitals, clinical practice and healthcare systems. In
      addition, there have been remarkable new opportunities in the way we teach,
      including changes in teaching methodology, educational technology, and a better
      understanding of how students actually learn. All of these advances have taken
      place during a period of enormous pressure to change residency programs,
      reorganize medical and clinical science, and question the very need for
      traditional departmental structures. It is likely that the new medical schools
      will emerge looking different from the older schools and they are likely to
      catalyze a period of curricular change.

PMID- 19768181
TI  - The medical educator in the 21st century: a personal perspective.
AB  - Academic faculty involved in medical education are set apart from educators in
      other fields by a different set of expectations and responsibilities. For a
      subgroup of such faculty, classified in this paper as clinician educators and
      educational leaders, their role as educators typically defines their primary
      academic contribution and mode of professional advancement. A variety of
      environmental factors, classified under the categories of changes in the
      healthcare system, changes in the educational environment, changes in the
      educational approach, and faculty pressures, present a series of challenges to
      these medical educators and to other teaching faculty at the beginning of the
      21st century. Ten such factors are identified in this article, followed by a
      series of suggested approaches for addressing these environmental challenges.

PMID- 19768183
TI  - Do the obese have lower body temperatures? A new look at a forgotten variable in
      energy balance.
AB  - Understanding the pathogenesis of obesity is now more important than ever, given
      the remarkable world-wide epidemic. This paper explores the potential role of
      core temperature in energy balance, and develops the hypothesis that basal
      temperature and changes in the temperature response in various situations
      contribute to the enhanced metabolic efficiency of the obese state. The argument
      is based on the important contribution that heat production makes in establishing
      the basal or resting metabolic rate, as well as on an analysis of the adaptive
      role played by changes in temperature in response to environmental challenge. If
      this hypothesis is validated, new therapeutic approaches may ensue.

PMID- 19768184
TI  - Introduction of the banquet speaker.

PMID- 19768182
TI  - Medical and genetic differences in the adverse impact of sleep loss on
      performance: ethical considerations for the medical profession.
AB  - The Institute of Medicine recently concluded that-on average-medical residents
      make more serious medical errors and have more motor vehicle crashes when they
      are deprived of sleep. In the interest of public safety, society has required
      limitations on work hours in many other safety sensitive occupations, including
      transportation and nuclear power generation. Those who argue in favor of
      traditional extended duration resident work hours often suggest that there are
      inter- individual differences in response to acute sleep loss or chronic sleep
      deprivation, implying that physicians may be more resistant than the average
      person to the detrimental effects of sleep deprivation on performance, although
      there is no evidence that physicians are particularly resistant to such effects.
      Indeed, recent investigations have identified genetic polymorphisms that may
      convey a relative resistance to the effects of prolonged wakefulness on a subset
      of the healthy population, although there is no evidence that physicians are over
      represented in this cohort. Conversely, there are also genetic polymorphisms,
      sleep disorders and other inter-individual differences that appear to convey an
      increased vulnerability to the performance-impairing effects of 24 hours of
      wakefulness. Given the magnitude of inter-individual differences in the effect of
      sleep loss on cognitive performance, and the sizeable proportion of the
      population affected by sleep disorders, hospitals face a number of ethical
      dilemmas. How should the work hours of physicians be limited to protect patient
      safety optimally? For example, some have argued that, in contrast to other
      professions, work schedules that repeatedly induce acute and chronic sleep loss
      are uniquely essential to the training of physicians. If evidence were to prove
      this premise to be correct, how should such training be ethically accomplished in
      the quartile of physicians and surgeons who are most vulnerable to the effects of
      sleep loss on performance without unacceptably compromising patient safety?
      Moreover, once it is possible to identify reliably those most vulnerable to the
      adverse effects of sleep loss on performance, will academic medical centers have
      an obligation to evaluate the proficiency of both residents and staff physicians
      under conditions of acute and chronic sleep deprivation? Should work-hour policy
      limits be modified to ensure that they are not hazardous for the patients of the
      most vulnerable quartile of physicians, or should the limits be personalized to
      enable the most resistant quartile to work longer hours? Given that the
      prevalence of sleep disorders has increased in our society overall, and increases
      markedly with age, how should fitness for extended duration work hours be
      monitored over a physician's career? In the spirit of the dictum to do no harm,
      advances in understanding the medical and genetic basis of inter-individual
      differences in the performance vulnerability to sleep loss should be incorporated
      into the development of work-hour policy limits for both physicians and surgeons.

PMID- 19768185
TI  - The search for life in the solar system.
AB  - In this presentation I give an overview of the long struggle to answer the age
      old question, does life exist anywhere else? The focus will be specifically on
      the search for life in the solar system, since this is the only region currently
      accessible to direct investigation. A hundred years ago many people believed that
      life, possibly even intelligent life, existed at the nearby planets Venus and
      Mars, and possibly elsewhere. The space age exploration of the planets has
      radically altered that view. We now know that Venus is a very hostile place, with
      no possibility for life, and that Mars is almost completely barren and very cold,
      with little prospect for life. The only remaining possibility appears to be in
      the interior of some of the moons of the outer planets where, due to an unlikely
      combination of factors, the conditions may be suitable for life.

PMID- 19768187
TI  - Introduction of the Jeremiah Metzger lecturer.

PMID- 19768188
TI  - The Jeremiah Metzger Lecture: gene therapy for inherited disorders: from
      Christmas disease to Leber's amaurosis.
AB  - This paper will focus on recent developments in the field of gene therapy for
      inherited disorders. From a historical perspective, this Metzger lecture is a
      follow-on to one presented by Dr. William Kelley in 1987, entitled "Current
      Status of Human Gene Therapy" (Transactions Am Clin. Climatol. Assoc. 99:152-169)
      (1). In 1987, gene transfer studies in human subjects were yet to be undertaken;
      the first clinical studies, infusion of genetically modified autologous T cells
      into two young girls with ADA-SCID, would not take place until 1990 (2). Today's
      lecture will summarize progress since that time in one area, that of in vivo gene
      transfer for genetic disease. I will describe progress in two areas, gene therapy
      for the bleeding disorder hemophilia B, and for a subset of retinal degenerative
      disorders termed Leber's congenital amaurosis, due to mutations in the gene
      encoding retinal pigment epithelium-specific 65 kilodalton protein (RPE65). This
      lecture will demonstrate the interconnected nature of progress in these two
      areas, as careful delineation of the obstacles in hemophilia led to the
      realization that success could be achieved in Leber's.

PMID- 19768189
TI  - Molecular pathogenesis of liver fibrosis.
AB  - Hepatic fibrosis is the final common pathway for most chronic liver diseases. The
      cell responsible for hepatic fibrosis appears to be the activated myofibroblast.
      The myofibroblast may be derived from quiescent hepatic stellate cells,
      epithelial to mesenhymal transition, or derived from bone marrow precursors.
      Studies in primary cultures of myofibroblasts and in mouse models of hepatic
      fibrosis have revealed several common pathophysiological mechanisms. Hepatic
      fibrosis is strongly associated with oxidative stress, increased transforming
      growth factor beta, hepatocyte death, and chronic inflammation. Finally, the
      reversal of fibrosis depends upon the elimination of the activated myofibroblast.

PMID- 19768190
TI  - Post-transplantation malignancy: a cell autonomous mechanism with implications
      for therapy.
AB  - Malignancy is a dreaded complication following organ transplantation.
      Immunosuppressive therapy-induced impairment of the host immune system is the
      prevailing hypothesis for the high incidence and aggressive progression of post
      transplant neoplasm. We summarize our observations supporting an autonomous
      cellular mechanism for cyclosporine and tacrolimus associated metastases.
      Cyclosporine conferred tumor invasiveness by a direct effect on the tumor cells
      and promoted metastases in T-, B-, and NK cell deficient SCID- beige mice, and
      anti-TGF-beta antibodies reduced metastases. Tacrolimus, another calcineurin
      inhibitor widely used in transplantation, induced TGF-beta secretion by tumor
      cells and promoted metastases in the SCID- beige mice. The immunosuppressive
      macrolide rapamycin reversed an invasive phenotype to a non-invasive one, reduced
      circulating levels of TGF-beta1 and prevented tumor growth and metastases in the
      immocompetant BALB/c mice and in the SCID-beige mice. Our studies, in addition to
      demonstrating a cell autonomous mechanism for tumor progression, advance TGF-beta
      blockade as an anti-tumor strategy.

PMID- 19768192
TI  - Ventricular scars and ventricular tachycardia.
AB  - Ventricular tachycardia (VT) is a life-threatening arrhythmia that is common to
      all forms of heart disease and an important cause of sudden death. Ventricular
      scars from infarction or replacement fibrosis provide a substrate for reentry
      that is a common cause. Understanding the pathophysiologic link between
      ventricular scars and ventricular tachycardia informs approaches to identify
      patients at risk, has led to development of methods to ablate the arrhythmia
      substrate that can be applied even in severe heart disease, and suggests future
      diagnostic and therapeutic strategies.

PMID- 19768191
TI  - How do kidney cells adapt to survive in hypertonic inner medulla?
AB  - The hypertonic inner medulla poses challenges to the cells that inhabit this area
      of the nephron. We employed discovery tools including proteomics and genomics to
      identify proteins that subserve the adaptive response. The gamma subunit of the
      Na/K-ATPase is critical to the survival of cells in hypertonic conditions, as
      silencing it increases osmosensitvity, and overexpression increases
      osmotolerance. The inner medullary collecting duct (IMCD) has high
      transepithelial resistance (TER). Proteins responsible for tight junction
      integrity are upregulated in hypertonic states. Multi PDZ protein 1 (MUPP1), a
      PDZ scaffolding protein, targets Claudin 4 to the tight junction. The silencing
      of either of these proteins decreases TER and renders the epithelium leaky. The
      accumulation of inert osmolytes is integral to the adaptive response. The genes
      involved are regulated by the transcription factor Tonicity Enhancer Binding
      Protein. An osmoregulated nuclear protein Nup88 is critical to the retention of
      this transcription factor in the nucleus and to the generation of the osmolytes.
      In summary, IMCD cells bring forth a coordinated response to hypertoncity that is
      necessary for cell survival and function of these cells in anisotonic conditions.

PMID- 19768193
TI  - The inherited autoinflammatory syndrome: a decade of discovery.
AB  - The hereditary autoinflammatory diseases arise from mutations of genes regulating
      the innate immune system. These rare disorders are well characterized, both
      clinically and in terms of their molecular pathogenesis. The recurrent attacks of
      febrile polyserositis of Familial Mediterranean Fever (FMF) are due to defective
      pyrin, a protein that down-regulates inflammation. The Hyperimmunoglobulinemia D
      Syndrome (HIDS), which mimics FMF, results from a genetically conferred
      deficiency of mevalonate kinase. TRAPS (TNF Receptor Associated Periodic
      Syndrome), formerly known as Familial Hibernian Fever, is caused by a defective
      membrane receptor for TNF. Three other hereditary disorders which overlap in
      their clinical expression - Familial Cold Autoinflammatory Syndrome, the Muckle
      Wells syndrome, and Neonatal Onset Multisystem Inflamatory Disease (NOMID) - are
      a consequence of gain-of-function mutations of the gene encoding cryopyrin, the
      scaffolding protein of the inflammasome. The PAPA syndrome (Pyogenic Arthritis,
      Pyoderma gangrenosum, Acne) results from mutations of a gene that increases the
      binding of its product (PSPSTPIP1) to pyrin, thereby blunting the inhibitory
      effect of pyrin on inflammasome activation.

PMID- 19768194
TI  - Ageing and the glomerular filtration rate: truths and consequences.
AB  - The process of glomerular filtration of plasma fluid has been known for over 160
      years and the measurement of the rate of its formation (glomerular filtration
      rate, GFR) has been possible for over 80 years. Studies conducted in the 1930's
      to the 1950's clearly established that GFR declines, perhaps inexorably, with
      normal ageing, usually beginning after 30-40 years of age. The rate of decline
      may accelerate after age 50-60 years. This decline appears to be a part of the
      normal physiologic process of cellular and organ senescence and is associated
      with structural changes in the kidneys. In the last decade a new paradigm has
      been introduced in which the true or measured GFR is estimated (eGFR) by formulas
      based on serum creatinine levels and in which these estimates are applied to the
      diagnoses of chronic kidney disease (CKD) in the general population. These
      criteria for diagnosis of CKD include an absolute threshold for eGFR, unadjusted
      for the effects of age on the normal values for eGFR. A consequence of these
      criteria has been to overstate the frequency of CKD in the general population and
      to generate many "false positive" diagnoses of CKD. This paper discusses the
      known effects of ageing on GFR and the consequences of using a classification
      system for defining CKD that does not take into account the normal decline of GFR
      with ageing.

PMID- 19768195
TI  - The Howard University Hospital experience with routineized HIV screening: a
      progress report.
AB  - BACKGROUND: Howard University Hospital (HUH) is the first hospital in the nation
      to have instituted a hospital-wide routine rapid HIV screening campaign as
      recommended by the CDC for healthcare settings. METHODS: HUH developed a protocol
      and implemented a hospital-wide routine HIV screening in October 2006. Rapid oral
      fluid-based HIV testing was conducted throughout the hospital using the OraSure
      OraQuick Advance Rapid HIV-1/2 Antibody Test. Patients with a preliminarily
      reactive test result were either referred for confirmatory testing or offered a
      Western Blot confirmatory test on-site and referred for follow-up care. This is a
      report on the progress of this program for the first eight months. RESULTS: Of
      the 9,817 patients offered HIV testing, 5,642 consented. The mean age of the
      screened population was 40.7 years. Ninety percent of the patients screened were
      black and 55% were female. A preliminarily reactive test result was identified in
      139 patients for a seroprevalence rate of 2.46%. Of these patients, 136, or 98%
      were black; 63% were male and 37% were female. HIV prevalence in the overall
      sample, among blacks, and among both black males and females peaked in the 40-54
      year old age group. Challenges were experienced initially in securing
      confirmatory tests. CONCLUSIONS: Hospital-wide routine HIV screening is both
      possible and productive. The routine HIV screening campaign instituted at Howard
      University Hospital has identified a significant number of previously
      unidentified HIV positive persons. Success in assuring confirmatory testing and
      transition to care improved as time progressed.

PMID- 19768197
TI  - Signal amplification in a lattice of coupled protein kinases.
AB  - The bacterium Escherichia coli detects chemical attractants and repellents by
      means of a cluster of transmembrane receptors and associated molecules.
      Experiments have shown that this cluster amplifies the signal about 35-fold and
      current models attribute this amplification to cooperative interactions between
      neighbouring receptors. However, when applied to the mixed population of
      receptors of wild-type E. coli, these models lead to indiscriminate methylation
      of all receptor types rather than the selective methylation observed
      experimentally. In this paper, we propose that cooperative interactions occur not
      between receptors but in the underlying lattice of CheA molecules. In our model,
      each CheA molecule is stimulated by its neighbours via their flexible P1 domains
      and modulated by the ligand binding and methylation states of associated
      receptors. We test this idea with detailed, molecular-based stochastic
      simulations and show that it gives an accurate reproduction of signalling in this
      system, including ligand-specific adaptation.

PMID- 19768201
TI  - Electrochemical techniques on sequence-specific PCR amplicon detection for point
      of-care applications.
AB  - Nucleic acid based analysis provides accurate differentiation among closely
      affiliated species and this species- and sequence-specific detection technique
      would be particularly useful for point-of-care (POC) testing for prevention and
      early detection of highly infectious and damaging diseases. Electrochemical (EC)
      detection and polymerase chain reaction (PCR) are two indispensable steps, in our
      view, in a nucleic acid based point-of-care testing device as the former, in
      comparison with the fluorescence counterpart, provides inherent advantages of
      detection sensitivity, device miniaturization and operation simplicity, and the
      latter offers an effective way to boost the amount of targets to a detectable
      quantity. In this mini-review, we will highlight some of the interesting
      investigations using the combined EC detection and PCR amplification approaches
      for end-point detection and real-time monitoring. The promise of current
      approaches and the direction for future investigations will be discussed. It
      would be our view that the synergistic effect of the combined EC-PCR steps in a
      portable device provides a promising detection technology platform that will be
      ready for point-of-care applications in the near future.

PMID- 19768202
TI  - Boron-doped diamond electrode: synthesis, characterization, functionalization and
      analytical applications.
AB  - In recent years, conductive diamond electrodes for electrochemical applications
      have been a major focus of research and development. The impetus behind such
      endeavors could be attributed to their wide potential window, low background
      current, chemical inertness, and mechanical durability. Several analytes can be
      oxidized by conducting diamond compared to other carbon-based materials before
      the breakdown of water in aqueous electrolytes. This is important for detecting
      and/or identifying species in solution since oxygen and hydrogen evolution do not
      interfere with the analysis. Thus, conductive diamond electrodes take
      electrochemical detection into new areas and extend their usefulness to analytes
      which are not feasible with conventional electrode materials. Different types of
      diamond electrodes, polycrystalline, microcrystalline, nanocrystalline and
      ultrananocrystalline, have been synthesized and characterized. Of particular
      interest is the synthesis of boron-doped diamond (BDD) films by chemical vapor
      deposition on various substrates. In the tetrahedral diamond lattice, each carbon
      atom is covalently bonded to its neighbors forming an extremely robust
      crystalline structure. Some carbon atoms in the lattice are substituted with
      boron to provide electrical conductivity. Modification strategies of doped
      diamond electrodes with metallic nanoparticles and/or electropolymerized films
      are of importance to impart novel characteristics or to improve the performance
      of diamond electrodes. Biofunctionalization of diamond films is also feasible to
      foster several useful bioanalytical applications. A plethora of opportunities for
      nanoscale analytical devices based on conducting diamond is anticipated in the
      very near future.

PMID- 19768203
TI  - Recent advances in nanostructured chemosensors and biosensors.
AB  - Over the past few decades the fabrication of nanoscale materials for use in
      chemical sensing, biomedical and biological analyses has proven a promising
      avenue. Nanomaterials show promise in such chemical and biological analysis
      mainly due to their highly tunable size- and shape-dependent chemical and
      physical properties. Furthermore, they exhibit unique surface chemistry, thermal
      stability, high surface area and large pore volume per unit mass that can be
      exploited for sensor fabrication. This review will discuss the chemical and
      physical properties of nanomaterials necessary for use as chemosensors and
      biosensors. It will also highlight some noteworthy recent avenues using nanoscale
      materials as scaffolds for chemosensing and biosensing. Nanomaterials that have
      proven to be useful for the fabrication of sensors, as reviewed herein, have
      compositions including metals, metal oxides, chalcogenides and polymers. Their
      structures range from nanoparticles, nanorods, and nanowires to nanoporous and
      core-shells. Examples of the different types of structures and compositions as
      well as sensors and biosensors fabricated from them will be described. Some
      nanomaterials are functionalized with various kinds of ligands and bioactive
      groups to produce sensitive and selective sensors for specific analytes. The
      combination of two or more types of nanostructures with core-shell type
      nanoassemblies and other composite structures, in addition to advantageous
      features enhancing sensitivity and response time of related sensors, are also
      discussed.

PMID- 19768204
TI  - Time-resolved lanthanide luminescence for lab-on-a-chip detection of biomarkers
      on cancerous tissues.
AB  - PDMS-based microfluidic devices combined with lanthanide-based immunocomplexes
      have been successfully tested for the multiplex detection of biomarkers on
      cancerous tissues, revealing an enhanced sensitivity compared to classical
      organic dyes.

PMID- 19768205
TI  - Cell separation by an aqueous two-phase system in a microfluidic device.
AB  - We generated an aqueous two-phase laminar flow in a microfluidic chip and used
      the system to isolate leukocyte and erythrocyte cells from whole blood cells. The
      microfluidic system reduced the effect of gravity in the aqueous two-phase system
      (ATPS). Poly(ethylene glycol) (PEG) and dextran (Dex) solutions were used as the
      two phases, and the independent flow rates of the solutions were both 2
      microL/min. When hydrophobic and hydrophilic polystyrene beads were introduced
      into the microfluidic device, the hydrophilic beads moved to the Dex layer and
      the hydrophobic beads to the interface between the two phases. In the case of
      living cells, Jurkat cells and erythrocytes moved more efficiently to the PEG and
      Dex layers, respectively, than they move in a conventional ATPS. When whole blood
      cells were inserted into the microfluidic chip, leukocytes could be separated
      from erythrocytes because erythrocytes moved to the Dex layer while leukocytes
      remained outside of this layer in the microfluidic system. The reported
      microfluidic chip for the whole blood cell separation can effectively be
      integrated into a Micro Total Analysis System designed for cell-based clinical,
      forensic, and environmental analyses.

PMID- 19768206
TI  - A versatile approach for assaying in vitro metallodrug metabolism using CE
      hyphenated with ICP-MS.
AB  - An informative analytical method, based on commercially available capillary
      electrophoresis (CE), inductively coupled plasma mass spectrometry (ICP-MS) and
      interface units, was developed for ascertaining possible metabolic
      transformations of metal-based drugs. Using a novel anticancer gallium compound,
      it was demonstrated that the drug remains intact in the simulated intestine
      juice. On the contrary, it undergoes a marked change in speciation (mostly, due
      to binding to transferrin) in human serum.

PMID- 19768207
TI  - RRLC-MS/MS-based metabonomics combined with in-depth analysis of metabolic
      correlation network: finding potential biomarkers for breast cancer.
AB  - A metabonomics strategy based on rapid resolution liquid chromatography/tandem
      mass spectrometry (RRLC-MS/MS), multivariate statistics and metabolic correlation
      networks has been implemented to find biologically significant metabolite
      biomarkers in breast cancer. RRLC-MS/MS analysis by electrospray ionization (ESI)
      in both positive and negative ion modes was employed to investigate human urine
      samples. The resulting data matrices were analyzed using multivariate analysis.
      Application of orthogonal projections to latent structures discriminate analysis
      (OPLS-DA) allowed us to extract several discriminated metabolites reflecting
      metabolic characteristics between healthy volunteers and breast cancer patients.
      Correlation network analysis between these metabolites has been further applied
      to select more reliable biomarkers. Finally, high resolution MS and MS/MS
      analyses were performed for the identification of the metabolites of interest. We
      identified 12 metabolites as potential biomarkers including amino acids, organic
      acids, and nucleosides. They revealed elevated tryptophan and nucleoside
      metabolism as well as protein degradation in breast cancer patients. These
      studies demonstrate the advantages of integrating metabolic correlation networks
      with metabonomics for finding significant potential biomarkers: this strategy not
      only helps identify potential biomarkers, it also further confirms these
      biomarkers and can even provide biochemical insights into changes in breast
      cancer.

PMID- 19768208
TI  - Nitric oxide monitoring in brain extracellular fluid: characterisation of Nafion
      modified Pt electrodes in vitro and in vivo.
AB  - A Nafion(5 pre-coats/2 dip-coats)-modified Pt sensor developed for real-time
      neurochemical monitoring has now been characterised in vitro for the sensitive
      and selective detection of nitric oxide (NO). A potentiodynamic profile at bare
      Pt established +0.9 V (vs. SCE) to be the most appropriate applied potential for
      NO oxidation. The latter was confirmed using oxyhaemoglobin and N(2), both of
      which reduced the NO signal to baseline levels. Results indicated enhanced NO
      sensitivity at the Nafion(5/2) sensor (1.67 +/- 0.08 nA microM(-1)) compared to
      bare Pt (1.08 +/- 0.20 nA microM(-1)) and negligible interference from a wide
      range of endogenous electroactive interferents such as ascorbic acid, dopamine
      and its metabolites, NO(2)(-) and H(2)O(2). The response time of 33.7 +/- 2.7 s
      was found to improve (19.0 +/- 3.4 s) when the number of Nafion layers was
      reduced to 2/1 and an insulating outer layer of poly(o-phenylenediamine) added.
      When tested under physiological conditions of 37 degrees C the response time of
      the Nafion(5/2) sensor improved to 14.00 +/- 2.52 s. In addition, the NO response
      was not affected by physiological concentrations of O(2) despite the high
      reactivity of the two species for each other. The limit of detection (LOD) was
      estimated to be 5 nM while stability tests in lipid (phosphatidylethanolamine;
      PEA) and protein (bovine serum albumin; BSA) solutions (10%) found an initial ca.
      38% drop in sensitivity in the first 24 h which remained constant thereafter.
      Preliminary in vivo experiments involving systemic administration of NO and L
      arginine produced increases in the signals recorded at the Nafion(5/2) sensor
      implanted in the striatum of freely-moving rats, thus supporting reliable in vivo
      recording of NO.

PMID- 19768209
TI  - Electrochemical properties of gas-generated silver nanoparticles in the presence
      of cyano- and chloride-containing compounds.
AB  - The electrochemistry of gas-generated naked Ag nanoparticles deposited on indium
      tin oxide covered glass plates is compared to bulk polycrystalline Ag. The nano
      specific electrochemistry has been identified and includes the preferential
      formation of beta-oxides. In 100 mM KOH supporting electrolyte, disruption of
      beta-oxide formation is exploited to test for the presence of diethyl
      cyanophosphonate. While in 8.0 M KOH, beta-oxide formation is enhanced leading to
      testing capabilities for 2-chloroethyl ethyl sulfide. These non-redox active
      compounds are effective simulants for the chemical warfare agents Tabun nerve
      agent and sulfur mustard, respectively.

PMID- 19768210
TI  - Simultaneous quantification of five bacterial and plant toxins from complex
      matrices using a multiplexed fluorescent magnetic suspension assay.
AB  - Proteotoxins such as ricin, abrin, botulinum neurotoxins type A and B (BoNT/A,
      BoNT/B) and staphylococcal enterotoxin B (SEB) are regarded as potential
      biological warfare agents which could be used for bioterrorism attacks on the
      food chain. In this study we used a novel immunisation strategy to generate high
      affinity monoclonal and polyclonal antibodies against native ricin, BoNT/A, and
      BoNT/B. The antibodies were used along with antibodies against SEB and abrin to
      establish a highly sensitive magnetic and fluorescent multiplex bead array with
      excellent sensitivities between 2 ng/L and 546 ng/L from a minimal sample volume
      of 50 microL. The assay was validated using 20 different related analytes and the
      assay precision was determined. Advancing the existing bead array technology, the
      novel magnetic and fluorescent microbeads proved amenable to enrichment
      procedures, by further increasing sensitivity to 0.3-85 ng/L, starting from a
      sample volume of 500 microL. Furthermore, the method was successfully applied for
      the simultaneous identification of the target toxins spiked into complex food
      matrices like milk, baby food and yoghurt. On the basis of our results, the assay
      appears to be a good tool for large-scale screening of samples from the food
      supply chain.

PMID- 19768211
TI  - Development of extractive electrospray ionization ion trap mass spectrometry for
      in vivo breath analysis.
AB  - In metabolomics studies and clinical diagnosis, interest is increasing in the
      rapid analysis of exhaled breath. In vivo breath analysis offers a unique,
      unobtrusive, non-invasive method of investigating human metabolism. To analyze
      breath in vivo, we constructed a novel platform of extractive electrospray
      ionization (EESI) ion trap mass spectrometry (ITMS) using a home-made EESI source
      coupled to a linear trap quadrupole mass spectrometer. A reference compound
      (authentic n-octyl amine) was used to evaluate effects of systematically varying
      selected characteristics of the EESI source on signal intensity. Under the
      optimized working conditions, metabolic changes of human bodies were in vivo
      followed by performing rapid breath analysis using the multi-stage EESI-ITMS
      tandem mass spectrometry platform. For nicotine, a limit of determination was
      found to be 0.05 fg mL(-1) (S/N = 3, RSD = 5.0 %, n = 10) for nicotine in aerosol
      standard samples; the dynamic response range was from 0.0155 pg mL(-1) to 155 pg
      mL(-1). The concentration of nicotine in the exhaled breath of a regular smoker
      was in vivo determined to be 5.8 pg mL(-1), without any sample pre-treatment. Our
      results show that EESI-ITMS is a powerful analytical platform to provide high
      sensitivity, high specificity and high throughput for semi-quantitative analysis
      of complex samples in life science, particularly for in vivo metabolomics
      studies.

PMID- 19768212
TI  - Surface plasmon resonance biosensor for direct detection of antibodies against
      human growth hormone.
AB  - A direct, label-free detection method of antibodies against the human growth
      hormone (anti-HGH) using a surface plasmon resonance (SPR) biosensor is reported.
      The sensing surface of the surface plasmon resonance biosensor chip (SPR-chip)
      was modified by covalent coupling of the human growth hormone (HGH) to the self
      assembled monolayer of 11-mercaptoundecanoic acid (MUA). HGH was immobilized via
      primary amine groups after activation of the MUA carboxyl groups with a mixture
      of N-hydroxysuccinimide (NHS), and N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide
      hydrochloride (EDC). The specific binding of monoclonal anti-HGH antibody on the
      HGH-modified surface was examined in the concentration range from 0.25 nM to 10
      microM. The experimentally observed detection minimum for anti-HGH was 2.47 nM. A
      single immunoassay cycle could be done within 30 min including the HGH and anti
      HGH association, HGH/anti-HGH complex dissociation and surface regeneration
      steps. The SPR biosensor response for repeatable detections of anti-HGH was
      highly reproducible and very stable. On the SPR-chip the formed HGH and anti-HGH
      complex (HGH/anti-HGH) could be gently dissociated and the sensing surface might
      be regenerated by 50 mM NaOH and 0.5% sodium dodecylsulfate (SDS) solution. Any
      changes in the original baseline level were detected during the 40 detection
      regeneration cycles. This means that damage of the immobilized HGH-based
      sensitive layer during regeneration was minimal. It was demonstrated that the
      developed SPR-chip could be stored for at least 21 days before use without
      considerable loss of sensitivity towards anti-HGH.

PMID- 19768214
TI  - On-capillary derivatization using a hybrid artificial neural network-genetic
      algorithm approach.
AB  - The first reported hybrid artificial neural network-genetic algorithm (ANN-GA)
      approach for the optimization of on-capillary dipeptide derivatization is
      presented. More specifically, genetic optimization proved valuable in the
      determination of effective network structure with three defined parameter inputs:
      (i) phthalic anhydride injection volume, (ii) time of injection, and (iii)
      voltage, for the maximum conversion of the dipeptide D-Ala-D-Ala by phthalic
      anhydride. Results obtained from the hybrid approach proved superior to an ANN
      model without GA optimization in terms of training data and predictive ability.
      The model developed will likely prove useful for the analysis of other organic
      based reaction systems.

PMID- 19768213
TI  - Interactions of sulfur-containing acridine ligands with DNA by ESI-MS.
AB  - The alkylating proficiency of sulfur-containing mustards may be increased by
      using an acridine moiety to guide the sulfur mustard to its cellular target. In
      this study, the interactions of a new series of sulfur-containing acridine
      ligands, some that also function as alkylating mustards, with DNA were evaluated
      by electrospray ionization mass spectrometry (ESI-MS). Relative binding
      affinities were estimated from the ESI-MS data based on the fraction of bound DNA
      for DNA/acridine mixtures. The extent of binding observed for the series of
      sulfur-containing acridines was similar, presumably because the intercalating
      acridine moiety was identical. Upon infrared multi-photon dissociation (IRMPD) of
      the resulting oligonucleotide/sulfur-containing acridine complexes, ejection of
      the ligand was the dominant pathway for most of the complexes. However, for AS4,
      an acridine sulfide mustard, and AN1, an acridine nitrogen mustard, strand
      separation with the ligand remaining on one of the single strands was observed.
      At higher irradiation times, a variety of sequence ions were observed, some
      retaining the AS4/AN1 ligand, which was indicative of covalent binding.

PMID- 19768215
TI  - Colorimetric cyanide detection using an azobenzene acid in aqueous solutions.
AB  - An azo-based dye (I) was designed for the detection of cyanide by utilizing a new
      indirect method. In the presence of Cu(II), compound I could give rise to visible
      red-to-yellow color change. The resultant yellow solution could change to red
      immediately upon the addition of trace cyanide, with the detection limit of 0.15
      ppm, but no changes were observed in the presence of other anions, including Cl(
      ), I(-), IO(3)(-), SO(4)(2-), NO(2)(-), Br(-), H(2)PO(4)(-), F(-), SCN(-),
      HSO(4)(-), ClO(4)(-) and CN(-), making compound I a selective and sensitive
      cyanide chemosensor.

PMID- 19768216
TI  - Potential-dependent surface denaturation of BSA in acid media.
AB  - In contrast to previous reports claiming bovine serum albumin (BSA) denaturation
      at mercury surfaces, recently it has been shown that BSA and other proteins do
      not denature as a result of adsorption to the mercury electrodes at alkaline and
      neutral pH values. In this pH range, constant current chronopotentiometry (CPS)
      with mercury or solid amalgam electrodes can be used to distinguish between
      native, denatured and damaged BSA. Here we show that at acid pH values (around pH
      4.5) native and denatured BSA yield almost the same CPS responses suggesting
      denaturation of native BSA at the electrode surface. Under these conditions BSA
      is, however, not denatured at the electrode at accumulation potentials (E(A)
      values) close to the potential of zero charge, but at E(A) values more negative
      than -0.8 V, after destabilization of the surface-attached BSA by
      electroreduction of some disulfide groups at about -0.48 V and by electric field
      effects at more negative potentials.

PMID- 19768217
TI  - Fluorescence detection of mercury ions in aqueous media with the complex of a
      cationic oligopyrene derivative and oligothymine.
AB  - A water-soluble complex of a cationic oligopyrene derivative,
      oligo(N(1),N(1),N(1),N(4),N(4),N(4)-hexamethyl-2-(4-(pyren-1-yl) butanoyloxy)
      butane-1,4-diaminium bromide), and oligothymine has been prepared. The
      fluorescence sensor based on this complex showed high sensitivity and selectivity
      toward mercury(II) ions in aqueous media. The transduction mechanism of this
      sensor is based on the fluorescence self-quenching of oligopyrene in water via
      the interchain pi-stacking arising from the specific thymine-Hg-thymine
      complexation. The detection limit of this sensor was measured to be as low as 5 x
      10(-9) mol L(-1). In addition, the fluorescent color change of the complex
      solution allows naked-eye detection of mercury(II) ions with an extremely low
      detection limit of 5 x 10(-6) mol L(-1).

PMID- 19768218
TI  - Identification of Pseudomonas aeruginosa using functional magnetic nanoparticle
      based affinity capture combined with MALDI MS analysis.
AB  - PA-IL is a galactophilic lectin that is found on the outer membrane of
      Pseudomonas aeruginosa. Pigeon ovalbumin (POA), a phosphoprotein, contains high
      levels of terminal Gal alpha(1-->4)Gal units. Thus, magnetic nanoparticles with
      immobilized POA can be used as affinity probes for P. aeruginosa, functioning via
      the recognition of galactophilic PA-IL. We fabricated POA-bound nanoparticles
      (NPs) by immobilizing POA onto the surface of core/shell magnetic iron
      oxide/alumina NPs via metal-phosphate chelation. We then used the generated NPs
      to probe target bacteria from complex samples. The trapped bacterial cells were
      characterized based on their mass peak profiles obtained from MALDI MS analyses.
      In addition, we confirmed the determination of P. aeruginosa using a proteomic
      strategy: combining the resultant MALDI MS/MS spectra of its tryptic digest with
      protein database searching. The feasibility of using this approach to rapidly
      characterize P. aeruginosa from clinical samples without the need to perform
      culturing steps was also demonstrated.

PMID- 19768219
TI  - Extraction of chemical information from complex analytical signals by a non
      negative independent component analysis.
AB  - Extraction of chemical information of the components from a complex analytical
      signal has been a great challenge in chemometrical studies for complex sample
      analysis. Independent component analysis (ICA) has been widely applied in complex
      signal separation, including the multicomponent overlapping signals in analytical
      chemistry. Difficulties, however, still exist in the application of ICA in
      chemical signal processing because chemical signals of different components are
      generally correlated and non-negative, instead of independence as hypothesized in
      ICA. In this study, a non-negative ICA method is proposed by means of a post
      rotation of the independent components (ICs) and applied to the extraction of the
      chemical information of the components from the signals of complex samples. Raman
      spectra of pharmaceutical tablets and gas chromatography-mass spectrometry (GC
      MS) data of cigarette smoke are qualitatively analyzed. The results show that the
      Raman spectrum of the active substance in the pharmaceutical tablets and the mass
      spectra of the components in the overlapping GC-MS signal can be effectively and
      accurately extracted by using the proposed method.

PMID- 19768220
TI  - Electrochemiluminescence detection based on ruthenium(II) tris(bipyridine)
      immobilised in sulfonic-functionalised titania nanoparticles by ion exchange
      strategy.
AB  - A novel Ruthenium(II) tris(bipyridine)-based solid-state electrochemiluminescence
      (ECL) sensor was developed in this paper. The sensor was fabricated by
      immobilising tris(2,2'-bipyridyl) ruthenium(II) (Ru(bpy)(3)(2+)) in sulfonic
      functionalised porous titania (TiO(2)-SO(3)H) nanoparticles via an ion exchange
      strategy, followed by employing environment friendly and stable biopolymer
      chitosan (CHIT) to entrap Ru(bpy)(3)(2+)/TiO(2)-SO(3)H onto the ITO electrode.
      The prepared ECL sensor exhibited excellent ECL behaviors and a wide linear range
      from 7.5 x 10(-9) to 2.5 x 10(-3) M (R = 0.98) with a detection limit of 1.67 x
      10(-10) M (S/N = 3) towards 2-(dibutylamino)-ethanol (DBAE) detection. In
      addition, it had good reproducibility, and the relative average deviation was
      0.95% of ECL intensity-time curve under continuous potential scanning for 34
      cycles. It also had good long-term stability for the DBAE detection. After being
      used in three weeks, the sensor was able to keep over 80% activity towards 2.5 x
      10(-4) M of DBAE. Fabrication of the ECL sensor by this method is simple and
      easy, and hence has potential applications in ECL analysis and detection.

PMID- 19768221
TI  - Fluorescence turn-on detection of iodide, iodate and total iodine using
      fluorescein-5-isothiocyanate-modified gold nanoparticles.
AB  - Selective turn-on fluorescence detection of I(-) was accomplished using
      fluorescein isothiocyanate-decorated gold nanoparticles (FITC-AuNPs). FITC
      molecules, which fluoresce strongly in an alkaline solution, were severely
      quenched when they were attached to the surface of AuNPs through their
      isothiocyanate group. Upon the addition of I(-), FITC molecules were detached
      because of I(-) adsorption on the surface of AuNPs. As a result, released FITC
      molecules were restored to their original fluorescence intensity. Because I(-)
      has a higher binding affinity to the surface of Au than do Br(-), Cl(-), or F(-),
      the FITC-AuNPs obviously have a higher selectivity toward I(-) than toward these
      other anions. Meanwhile, after IO(3)(-) was reduced to I(-) with ascorbic acid,
      the detection of IO(3)(-) was successfully achieved using the FITC-AuNPs. Under
      an optimum pH and AuNP concentration, the lowest detectable concentrations of I(
      ) and IO(3)(-) using this probe were 10.0 and 50.0 nM, respectively. The FITC
      AuNPs provide a number of advantages, including easy preparation, selectivity,
      sensitivity, and low cost. This unique probe was applied to an analysis of the
      total iodine in edible salt and seawater.

PMID- 19768222
TI  - Cisplatin-based DNA sensing with enhanced current response.
AB  - A novel electrochemical technique for DNA detection has been developed by a
      simple combination cisplatin and a glassy carbon electrode. The complexation of
      cisplatin with DNA caused suppression of the electroreduction of cisplatin owing
      to the steric hindrance and, subsequently, the electrolytic current for reducing
      proton that is catalyzed by the platinum deposited on the glassy carbon electrode
      by the electroreduction of cisplatin. Thus the DNA content was determined from
      the decrease in the catalytic activity of the electrode: an enhanced current
      response for measuring the current for reducing proton as compared with that for
      reducing cisplatin itself could provide the highly-sensitive measurement of
      cisplatin. The detection limit for herring DNA was as low as 0.1 ng/mL.

PMID- 19768223
TI  - Selective sensor utilizing a thin monolayer of b-oriented silicalite-1 crystals
      magneto-elastic ribbon assembly.
AB  - This report presents the development of new selective gas sensors utilizing a b
      oriented silicalite-1 layer-magneto-elastic ribbon assembly. The key principle
      for the operation of these sensors is monitoring the changes in the resonance
      frequency of the Metglas strip in relation to the concentration of a component in
      the gas phase. This technique provides a simple way for monitoring the effects of
      the amount of adsorbed gases in the silicalite-1 coating. The thickness of the
      zeolite layer is that of a single crystal. The silicalite-1 crystals are oriented
      in the b-direction, meaning that the straight channels are perpendicular to the
      sensor surface, which is confirmed by X-ray diffraction (XRD) analysis. The
      sensor was able to repeatedly sense carbon dioxide in air and could discriminate
      between linear and branched hydrocarbons. The sensor was able to detect n-butane,
      while it did not respond to the presence of iso-butane, indicating sensing
      selectivity.

PMID- 19768224
TI  - Quantification of C-reactive protein in human blood plasma using near-infrared
      Raman spectroscopy.
AB  - In this paper a new biological application of quantitative Raman spectroscopy is
      proposed. Native human plasma C-Reactive Protein (CRP) is used as a clinical
      biomarker of bacterial infection and tissue damage. The protein circulates in the
      blood and the concentration rises as inflammation occurs. For the first time the
      Raman spectrum of CRP in a buffered aqueous solution has been acquired using 785
      nm excitation. The concentration of CRP has been measured in blood plasma, using
      near-infrared (NIR) Raman spectroscopy. Spectra were acquired with an in situ
      Inspector Raman spectrometer using 785 nm excitation. Raman spectra were
      collected from blood plasma drawn from 40 individuals. Quantitative predictions
      of CRP were made by means of Partial Least Squares (PLS) analysis and a variable
      selection method Interval PLS (IPLS). The similarity of the features in the PLS
      regression vector to that of CRP's Raman spectrum illustrates that the prediction
      is sensitive to the molecular information carried by the Raman scattered light.
      The IPLS algorithm is applied to optimize the calibration model to near clinical
      accuracy. This demonstrates the feasibility of using Raman spectroscopy for
      quantitative measurements of CRP in blood plasma.

PMID- 19768225
TI  - Facile chemiluminescence assay for antioxidative properties of vegetable lipids:
      fundamentals and illustrative examples.
AB  - The general approach disclosed herein opens the new possibilities of exploiting
      the oxidation processes followed by chemiluminescence (CL) emission for the
      assessment of an antioxidant potential of natural lipid materials and enables
      determination of the amount and strength of lipid-borne antioxidants in one
      experiment. The reliability of the analytical procedure is completely unaffected
      by an inevitable entering of oxidizable lipid portions into the probe
      chemiluminescent mixture, which is exemplarily illustrated for the case of
      vegetable oils which served as sources of antioxidant-containing lipids. As a
      matter of fact, the difference in the effective radical-scavenging rate
      constants, determined for the antioxidative constituents of the sunflower and
      corn oils, perfectly matches the distinction of their qualitative tocopherol
      contents. In addition to the antiradical activity of lipid samples, the
      antioxidant potential of the latter may be modified by their influence on
      hydroperoxide stability, as it has been also demonstrated in the present work.

PMID- 19768226
TI  - Graphite nanosheet-based composites for mediator-free H2O2 biosensor.
AB  - Graphite nanosheet (GNS)-Nafion composites were prepared for the immobilization
      of hemoglobin (Hb) to construct a mediator-free H(2)O(2) biosensor. Scanning
      electron microscopy (SEM), UV-vis spectroscopy and Fourier transform infrared
      spectroscopy were used to characterize the Hb-GNS-Nafion composite film. Due to
      good biocompatibility of the composite film, immobilized Hb retained its native
      structure. The Hb-GNS-Nafion composite film-modified electrodes showed direct
      electrochemistry with a fast electron-transfer rate (6.63 s(-1)) and high
      electrocatalytic activity to the reduction of hydrogen peroxide (H(2)O(2)). The
      resulting biosensor exhibited a high sensitivity of 412.7 mA M(-1) cm(-2), a low
      detection limit of 2.0 x 10(-7) M, and a small apparent Michaelis-Menten constant
      of 37 microM. These results were comparable or superior to the biosensors based
      on the carbon nanofiber (CNF)- and carbon nanotube (CNT)-based biosensors. Due to
      the lower cost of GNSs, the GNS-based composite can combine with other redox
      proteins and widely apply in mediator-free biosensors, bioelectronics and biofuel
      cells.

PMID- 19768227
TI  - Calix[4]arene crown-4 ether modified glassy carbon electrode for electrochemical
      determination of norepinephrine.
AB  - A sensitive and selective electrochemical method for the determination of
      norepinephrine (NE) was developed by using a calix[4]arene crown-4 ether (CACE)
      film modified glassy carbon electrode (GCE). The fabrication of the CACE film and
      its electrocatalytic effect for electrochemical oxidation of NE were investigated
      by electrochemical impedance spectroscopy (EIS) and voltammetric methods. It was
      found that the electrochemical behavior of NE on the CACE film modified electrode
      depended on the film thickness of CACE. Based on the electrochemical data, the
      CACE film surface coverage (theta), the charge transfer number (z) and the amount
      of the surface-bound NE (Gamma) were calculated. The effects of the experimental
      variables such as the solution pH and the applied potential were investigated for
      optimum analytical performance. Excellent linear relationships were obtained in
      two concentration ranges of NE: one was from 0.55 to 9.7 microM and the other was
      9.7 to 230 microM. The detection limit (S/N = 3) of NE obtained by steady-state
      amperometry was 0.28 microM. The relative standard deviation (RSD) for 10
      successive measurements of 0.05 mM NE was 2.2%. This method could be applied for
      the direct determination of NE in injection samples. In addition, effects of
      possible interferences (e.g. ascorbic acid, AA) were investigated. The present
      work provides an effective method for amperometric determination of NE by using a
      CACE modified electrode.

PMID- 19768228
TI  - Smoothly shifting fluorescent windows: a tunable "off-on-off" micellar sensor for
      pH.
AB  - The position of the window in an "off-on-off" fluorescent pH sensor may be
      shifted at will along a pH axis by changing the overall charge of the micellar
      container. This is obtained by using non-ionic Triton X-100 as the surfactant,
      and by increasing the molar fraction of the anionic sodium dodecyl sulfate
      (chi(SDS)) as co-surfactant, with pyrene as the fluorophore and a lipophilic
      tertiary amine and a lipophilic pyridine as pH-switchable quenchers. As the
      negative micellar charge increases by increasing chi(SDS), the observed pKa of
      the protonated bases move to higher pH values, followed by the dumb-bell shaped
      "off-on-off" fluorescence intensity vs. pH profile.

PMID- 19768229
TI  - A photoluminescent nanocrystal-based signaling protocol highly sensitive to nerve
      agents and highly toxic organophosphate pesticides.
AB  - A photoluminescent II-VI group semiconductor nanocrystal (NC)-based signaling
      platform composed of thioglycolic acid capped CdS NCs and acetylcholinesterase
      acetylthiocholine enzyme catalytic reaction system was developed that was shown
      to be highly sensitive to nerve agents and toxic organophosphate pesticides with
      detection limits down to sub-nM levels. This new sensing protocol does not
      require troublesome conjugation of biomacromolecules onto the surface of NCs.

PMID- 19768230
TI  - Boronate affinity monolith for highly selective enrichment of glycopeptides and
      glycoproteins.
AB  - A novel boronate affinity monolith, poly(3-acrylamidophenylboronic acid-co
      ethylene dimethacrylate) (AAPBA-co-EDMA), was prepared in 530 microm capillaries
      by a one-step in situ polymerization procedure using a pre-polymerization mixture
      consisting of functional monomer 3-acrylamidophenylboronic acid, cross-linker
      ethylene dimethacrylate, porogenic solvent methanol with added poly(ethylene
      glycol) 20,000 (PEG 20,000) and initiator azobisisobutyronitrile (AIBN). The
      preparation of the monolith was optimized by investigating the ratio of
      functional monomer to cross-linker and the effect of poly(ethylene glycol)
      molecular weight. The resulting boronate monolith was used as a sorbent for
      polymer monolith microextraction (PMME). Using nucleosides as the testing
      analyte, the extraction performance of this boronate monolith towards glycol
      containing compounds was examined. Finally, the boronate monolith was applied for
      selective enrichment of glycopeptides and glycoproteins.

PMID- 19768233
TI  - Prevalence and risk factors associated with smoking among school children,
      Southern Brazil.
AB  - OBJECTIVE: To estimate the prevalence of smoking among students and associated
      factors. METHODS: Secondary data from the Vigescola Survey, conducted in the
      cities of Curitiba, Florianopolis and Porto Alegre (Southern Brazil) between 2002
      and 2004, were used. Sample comprised 3,690 school children, aged between 13 and
      15 years, and enrolled in the 7th and 8th grades of primary school and 1st grade
      of high school, in public and private schools. Weighted proportions and odds
      ratio (OR) were estimated and multiple logistic regression was used to analyze
      results. RESULTS: Smoking prevalence rates were 10.7% (95% CI: 10.2;11.3) in
      Florianopolis, 12.6% (95% CI: 12.4;12.9) in Curitiba and 17.7% (95% CI:
      17.4;18.0) in Porto Alegre. Risk factors associated with smoking among
      schoolchildren in Curitiba were: female sex (OR=1.49), smoking father (OR=1.59),
      smoking friends (OR=3.46), exposure to secondhand tobacco smoke outside the home
      (OR=3.26), and having some object with cigarette brand logos (OR=3.29). In
      Florianopolis, variables associated with smoking were: female schoolchildren
      (OR=1.26), having smoking friends (OR=9.31), exposure to secondhand tobacco smoke
      at home (OR=2.03) and outside the home (OR=1.45) and having seen advertisements
      on posters (OR=1.82). In Porto Alegre, variables associated with tobacco use
      among school children were: female sex (OR=1.57), aged between 14 years (OR=1.77)
      and 15 years (OR=2.89), smoking friends (OR=9.12), exposure to secondhand tobacco
      smoke at home (OR=1.87) and outside the home (OR=1.77) and having some object
      with cigarette brand logos (OR=2.83). CONCLUSIONS: Smoking prevalence among
      school children aged between 13 and 15 years is high. Factors significantly
      associated with it and common to the three capitals were as follows: having
      smoking friends and being exposed to environmental smoke outside the home.

PMID- 19768234
TI  - Disability relating to basic and instrumental activities of daily living among
      elderly subjects.
AB  - OBJECTIVE: To assess the prevalence of disability and associated factors in
      elderly, by focusing on basic and instrumental activities of daily living.
      METHODS: This was a cross-sectional study on 598 subjects aged 60 years or over
      who were selected through two-stage cluster sampling in Pelotas, Southern Brazil,
      between 2007 and 2008. Basic and instrumental activities were evaluated using the
      Katz Index and the Lawton Scale, respectively. Disability relating to each domain
      was defined as the need for partial or total assistance to perform at least one
      activity of daily living. Poisson regression with robust variance was used in the
      crude and adjusted analyses, taking the cluster sampling into account. RESULTS:
      The prevalence of disability relating to basic activities was 26.8% (95% CI:
      23.0; 30.8). The lowest proportion of independence was in relation to controlling
      the urination and/or evacuation functions. In relation to instrumental
      activities, the prevalence of disability was 28.8% (95% CI: 24.5; 33.1),
      particularly in relation to moving around using means of transportation. A high
      proportion of the elderly subjects (21.7%) presented more than one instrumental
      activity with disability. In relation to basic activities, the greatest
      proportion presented dependence for only one activity (16.6%). In the adjusted
      analysis, disability relating to basic activities was associated with non-white
      skin color (p=0.01) and increasing age (p<0.001). Disability relating to
      instrumental activities was only associated with increasing age (p<0.001).
      CONCLUSIONS: The association between disability relating to basic and
      instrumental activities and increasing age is an indicator of importance for
      enabling the health services to plan actions that aim to prevent or delay the
      occurrence of disability, thereby ensuring independence and better quality of
      life among the elderly.

PMID- 19768235
TI  - Leisure-time physical inactivity in adults and factors associated.
AB  - OBJECTIVE: To analyze the association between leisure-time physical inactivity
      and sociodemographic factors and risk or protection factors for chronic
      noncommunicable diseases among adults. METHODS: Cross-sectional study comprising
      adults aged 18 years and older (n = 1,996). Data was obtained from the
      Surveillance System for Risk Factors for Chronic Noncommunicable Diseases
      (CNCDs), a random-digit-dialed telephone survey carried out in the city of
      Florianopolis, southern Brazil, in 2005. There were studied sociodemographic, and
      behavioral protective and risk factors. Results of the multivariate analysis of
      the association between leisure-time physical inactivity and independent
      variables were expressed as prevalence ratios. RESULTS: The prevalence of leisure
      time physical inactivity was 54.6% (47.3% among men, 61.4% among women). After
      adjustment, among men, higher physical inactivity was positively associated with
      older age, lower schooling, and inversely associated with working status; and
      lower physical inactivity was associated with alcohol abuse, regardless of age,
      schooling, and work status. Among women, higher leisure-time physical inactivity
      was positively associated with schooling (less than 12 years of education) and
      working status. The analyses adjusted for schooling and work status showed higher
      physical inactivity among those women reporting consuming fruits and vegetables
      less than five times a day and whole milk. CONCLUSIONS: Factors associated with
      leisure-time physical inactivity were different among men and women. Among women,
      physical inactivity was associated to risk factors for chronic diseases,
      especially eating habits. Among men, physical inactivity was associated to
      sociodemographic factors.

PMID- 19768236
TI  - Knowledge, attitudes, and practices related to Pap test by women, Northeastern
      Brazil.
AB  - OBJECTIVE: To assess the knowledge, attitudes and practices of women related to
      the Pap test and the association between these behaviors and sociodemographic
      characteristics. METHODS: A household survey with quantitative approach was
      conducted. A total of 267 women aged 15 to 69 years, randomly selected in a
      stratified manner, living in the city of Sao Jose de Mipibu, Northeastern Brazil,
      were interviewed in 2007. A questionnaire consisting of pre-coded open questions
      was administered and answers were described and analyzed, as for adequacy of
      knowledge, attitudes, and practices of women regarding the Pap test. Tests of
      association were carried out between sociodemographic characteristics and
      behaviors studied at a 5% significance level. RESULTS: Although 46.1% of the
      women interviewed showed adequate knowledge about the Pap test, a significantly
      higher proportion of adequacy was seen regarding attitudes and practices, 63.3%
      and 64.4%, respectively. Higher schooling was associated with adequacy of
      knowledge, attitudes, and practices. The main barriers to the Pap test were
      negligence, non-requesting by their physicians, and shame. CONCLUSIONS: The
      physician is the main source of information about the Pap test. However, women
      who more often attend medical visits, despite their good practice, show low
      adequacy of knowledge and attitudes related to the Pap test, which indicates that
      they are not receiving appropriate information on the test's purpose, advantages
      and benefits to women's health.

PMID- 19768237
TI  - Performance of primary healthcare services in tuberculosis control.
AB  - OBJECTIVE: To assess the access to tuberculosis treatment in healthcare services
      with Programa Saude da Familia (PSF - Family Health Program) and at a reference
      outpatient clinic. METHODS: A descriptive inquiry was carried out in 2007 with
      106 patients who received tuberculosis treatment through the PSF or the reference
      outpatient clinic in Campina Grande, Northeastern Brazil, from July 2006 to
      August 2007. To assess the health services, the instrument Primary Care
      Assessment Tool was used, validated and adapted to assess tuberculosis care in
      Brazil. The main variables analyzed referred to the transportation and distance
      to the service and patients' supervision. RESULTS: Of the 106 patients, 83.9%
      performed self-administered treatment and 16.0% received supervised treatment.
      The indicators from the PSF units and from the reference outpatient clinic that
      were similar (p>0.05) were: 65.1% 'losing half work day to attend the medical
      visit'; 65.0% 'having to use motorized transport'; 50.0% 'always having to pay
      for motorized transport'; and 69.0% 'not receiving treatment at healthcare units
      near home'. The indicators 'using motorized transport', 'paying for transport to
      attend the medical visit' and 'receiving treatment near home' were statistically
      different (p<0.05) between the services. Standardized and non-standardized
      Cronbach's alpha coefficients were, respectively, 0.7275 and 0.7075, based on the
      eight items of the questionnaire. CONCLUSIONS: Although the city has 85 PSF
      teams, supervised treatment was carried out by few health workers. Although the
      tuberculosis treatment is offered by the public health service, it still
      represents a cost to the patients, due to the distance to the healthcare service
      and losing half work day in order to attend medical visits.

PMID- 19768238
TI  - Mechanisms of microregulation of private hospitals by health plan operators.
AB  - OBJECTIVE: To analyze the mechanisms employed by health plan operators for
      microregulation of clinical management and health care qualification within care
      providing hospitals. METHODS: A nation-wide cross-sectional study was carried
      out. The universe consisted of hospitals which provided care to health plan
      operators in 2006. A sample of 83 units was selected, stratified by Brazilian
      macroregion and type of hospital. Data were obtained by means of a questionnaire
      administered to hospital managers. RESULTS: Microregulation of hospitals by
      health plan operators was minimal or almost absent in terms of health care
      qualification. Operator activity focused predominantly on intense control of the
      amount of services used by patients. Hospitals providing services to health plan
      operators did not constitute health micro-systems parallel or supplementary to
      the Sistema Unico de Saude (SUS - Brazilian National Health System). The private
      care-providing hospitals were predominantly associated with SUS. However, these
      did not belong to a private care-provider network, even though their service
      usage was subject to strong regulation by health plan operators. Operator
      intervention in the form of system management was incipient or virtually absent.
      Roughly one-half of investigated hospitals reported adopting clinical directives,
      whereas only 25.4% reported managing pathology and 30.5% reported managing cases.
      CONCLUSIONS: Contractual relationships between hospitals and health plan
      operators are merely commercial contracts with little if any incorporation of
      aspects related to the quality of care, being generally limited to aspects such
      as establishment of prices, timeframes, and payment procedures.

PMID- 19768239
TI  - [Nutrition never goes out of fashion].

PMID- 19768240
TI  - [Interethnic marriage of Japanese-Brazilians associated with less healthy food
      habits and worse cardiometabolic profile].
AB  - OBJECTIVE: Interethnic marriage between nikkey Brazilians and non-nikkey
      Brazilians may favor the westernization of diet. Dietary consumption, clinical
      data and frequencies of metabolic diseases were compared in a Japanese-Brazilian
      population, with intraethnic or interethnic marriage. METHODS: T test, Mann
      Whitney, chi-square and Person coefficient were used. RESULTS: Among 1009
      Japanese-Brazilians there were 18.9% of interethnic marriage, being more frequent
      among nikkey men. These showed higher means of BMI, waist, blood pressure,
      glycemia and triglyceridemia than women. Overall frequencies of obesity,
      hypertrigliceridemia and metabolic syndrome were 47.7%, 68.1% and 45.2%, being
      higher in interethnic than intraethnic marriage. Comparing individuals with
      interethnic marriages, hypertriglyceridemia was more common among men while low
      HDL among women. Energy, fat, groups of alcohol, sweets and oils were higher in
      interethnic marriage. Individuals with intraethnic marriage consumed more
      carbohydrate, proteins, fibers, vitamins, minerals, vegetables, fruits/juice,
      cereals and missoshiru. Comparing individuals with interethnic marriages, nikkey
      men showed a more westernized dietary pattern than nikkey women. CONCLUSION:
      Interethnic marriage was associated with less healthy food habits and worse
      cardiometabolic profile.

PMID- 19768241
TI  - [Gene-nutrient interaction and its association with obesity and diabetes
      mellitus].
AB  - Nutritional genomics evaluates the effects of genetic variation in the
      interaction between diet and chronic diseases. The aim of this manuscript was to
      review the most important genetic polymorphisms associated with obesity, diabetes
      mellitus, and dietary factors. The main interactions among genetic polymorphisms
      and diet were: for obesity: interleukin-6 (IL-6) with daily intake; peroxisome
      proliferator-activated receptor gamma 2 (PPAR-gama2) and fat mass and obesity
      associated (FTO) with fat intake; beta-adrenergic receptor 2 (ADRB2) and
      melanocortin receptor 4 (MCR4) with carbohydrate intake; or reduction in body
      weight: uncoupling proteins (UCPs) with restriction of energy; for leptinemia:
      leptin receptor (LEPR) with restriction of energy; for diabetes mellitus: PPAR
      gama2 with fat intake; for hypertriglyceridemia: fatty acid-binding protein 2
      (FABP2) with fat intake. The data demonstrated suggest that nutritional genomics
      is important for the development of obesity and diabetes mellitus.

PMID- 19768243
TI  - [Dietary intake and dyslipidemia arising from combination antiretroviral therapy
      for HIV infection: a systematic review].
AB  - To review and synthesize the available scientific evidence on the relationship
      between dietary intake and dyslipidemias in HIV-infected patients in combination
      antiretroviral therapy (ART). A systematic review of literature was carried out.
      Original and published studies were investigated and two categories of dietary
      exposure were considered: energy and nutrient intake, and consumption of a test
      diet. A narrative review of included studies was conducted. The findings were
      summarized according to category of metabolic outcomes (effect on total
      cholesterol and LDL-c, effect on HDL-c and effect on triglycerides). Twenty
      original studies were included in this review, being 13 clinical trials and 7
      observational studies. Omega-3 fatty acid supplementation led to a significant
      decrease in triglycerides. There was very little evidence on the effectiveness of
      dietary interventions for the prevention and control of dyslipidemias in HIV
      infected patients receiving ART.

PMID- 19768242
TI  - [Dietary fibers: current trends and health benefits in the metabolic syndrome and
      type 2 diabetes].
AB  - Dietary fiber may contribute to both the prevention and treatment of type 2
      diabetes mellitus (T2DM). In epidemiological studies the intake of insoluble
      fiber, but not the intake of soluble fiber, has been inversely associated with
      the incidence of T2DM. In contrast, in postprandial studies, meals containing
      sufficiently quantities of beta-glucan, psyllium, or guar gum have decreased
      insulin and glucose responses in both healthy individuals and patients with T2DM.
      Diets enriched sufficiently in soluble fiber may also improve overall glycemic
      control in T2DM. Insoluble fiber has little effect on postprandial insulin and
      glucose responses. Fiber increases satiety. In some studies, insoluble fiber has
      been associated with less weight gain over time. Limited cross-sectional evidence
      suggests an inverse relationship between intake of cereal fiber and whole-grains
      and the prevalence of the metabolic syndrome. Although long-term data from trials
      focusing on specifically dietary fiber are lacking, meeting current
      recommendations for a minimum fiber intake of 25 g/d based on a diet rich in
      whole grains, fruits and legumes will probably decrease the risk of obesity, the
      metabolic syndrome and T2DM.

PMID- 19768244
TI  - Infant feeding practices, childhood growth and obesity in adult life.
AB  - Child health is widely affected by nutritional status, and there is growing
      interest surrounding the possibility that child nutritional status and infant
      feeding practices may be linked to obesity in adulthood, increasing risks of
      metabolic complications. Prospective studies enable appropriate investigation and
      evaluation of the determinants of childhood development. The present paper
      therefore aimed to provide a review of the main evidence to date from
      longitudinal studies concerning the associations of infant feeding practices,
      patterns of childhood growth and nutritional status exhibited in adult life.

PMID- 19768245
TI  - [Hyperhomocysteinemia and cardiometabolic risk].
AB  - Hyperhomocysteinemia, when considered as a causal factor of vascular diseases,
      has been subject of much discussion. Case-control, retrospective and prospective
      studies have identified a relationship between high plasma concentrations of
      homocysteine and vascular disease. The aim of the present review was to better
      understand the interrelation between plasma concentrations of homocysteine and
      vascular diseases, as well as the involvement of classical risk factors for the
      disease: genetic factors, such as mutations in the genes that codify the enzymes
      involved in the metabolism of homocysteine, and nutritional factors, such as
      complex B vitamin deficiency. The publications of the main databases in health
      were consulted for the period 1962 to 2009. The mechanism by which
      hyperhomocysteinemia acts as a risk factor for vascular diseases still has not
      been fully clarified, but involvement of endothelial dysfunction and lipid
      peroxidation is suggested. The treatment of hyperhomocysteinemia is based on food
      supplements and medication, with folic acid and vitamins B6 and B12.

PMID- 19768246
TI  - [Vitamins and minerals with antioxidant properties and cardiometabolic risk:
      controversies and perspectives].
AB  - Oxygen reactive species (ROS) are generated during cellular processes. In excess,
      they may cause damages to the cell. Oxidative stress is an imbalance in the redox
      state that favors oxidation. Endogenous enzymes and some vitamins and minerals
      participate in the plasma antioxidant defense. Vitamin E is found in the plasma
      and in the LDL particle, avoiding lipid peroxidation. Observational studies
      reported an inverse association between vitamin E consumption and cardiometabolic
      (CM) risk. However, clinical trials were not able to prove the efficacy of its
      supplementation on CM endpoints. Vitamin C participates in the vitamin E
      regeneration system, keeping the plasma's antioxidant potential. Data about
      beneficial effects of its supplementation in CM risk reduction are inconclusive.
      The antioxidant activity of carotenoids is partially responsible for its
      protective role against cardiovascular diseases and cancer. Supplementation of
      this nutrient did not provide consistent findings in terms of CM risk reduction.
      Recently, zinc and selenium's participation in the antioxidant defense has been
      studied, yet its supplementation in individuals with normal levels and adequate
      ingestion of these nutrients does not seem necessary. In summary, the role of
      these micronutrients for CM risk is still very controversial. Epidemiological
      studies suggest that diets rich in antioxidants, or simply in fruit and
      vegetables intake, can reduce CM risk. Further studies are needed before
      recommending antioxidant supplements for this purpose.

PMID- 19768247
TI  - [Glycemic index and glycemic load in the prevention and treatment of type 2
      diabetes mellitus].
AB  - The tight glycemic control can prevent and/or delay the development of chronic
      complications of diabetes mellitus (DM). Dietary carbohydrates are the main
      determinant of postprandial blood glucose and glycemic index (GI) and glycemic
      load are used to predict blood glucose response to foods. The aim of this paper
      was to critically review the role of low GI diets in type 2 diabetes mellitus
      (T2DM) prevention and metabolic control. The risk for development of T2DM with
      high GI diets ranged from 1.21 to 1.59.The reduction from 12-32 units in the GI
      of diets decreased 0.39-0.50% in HbA1c values. However, the effects of these
      diets on lipid profile and body weight in patients with T2DM remain
      controversial. In conclusion, the current evidence indicates that the inclusion
      of GI in the dietary planning for patients with T2DM contributes to the
      improvement of glycemic control.

PMID- 19768248
TI  - [Hormonal and inflammatory impact of different dietetic composition: emphasis on
      dietary patterns and specific dietary factors].
AB  - Healthy dietary pattern, characterized by the consumption of fruits, vegetables,
      white meats, skim dairy products, nuts and moderate intake of vegetable oils and
      alcohol, is an important factor for a lower risk of chronic disease such as
      obesity, metabolic syndrome and cardiovascular disease. This beneficial effect
      can be explained, at least partially, by its modulating role on biomarkers of
      insulin sensitivity and atherosclerosis as well as of inflammation and
      endothelial function. On the other hand, the intake of specific dietary factors,
      such as unsaturated fatty acids (oleic and alpha-linolenic) and micronutrients
      with antioxidant properties (vitamins A, E and C; selenium, zinc) has been
      discussed, due to its potential protector action due to chronic disease
      occurrence and its possible profits in hormonal, metabolic and inflammatory
      regulations that these dietetic factors can provide within a nutritional
      treatment to obesity and metabolic syndrome.

PMID- 19768249
TI  - [Control of adipogenesis by fatty acids].
AB  - Obesity is one of the major Public Health problems. Obese individuals are more
      susceptible to develop cardiovascular diseases and type 2 diabetes mellitus. The
      obesity results from the increase in size and number of the adipocytes. The
      balance between adipogenesis and adiposity determines the degree of obesity.
      Mature adipocytes secrete adipokines, such as TNFalpha, IL-6, leptine and
      adiponectin, and lipokine, the palmitoleic acid omega-7. The production of
      adipokines is increased in obesity, contributing to the onset of peripheral
      insulin resistance. The knowledge about the molecular events that regulate the
      differentiation of pre-adipocytes and mesenchymal stem cells into adipocytes
      (adipogenesis) is important for the comprehension of the genesis of obesity.
      Activation of transcription factor PPARgamma plays an essential role in the
      adipogenesis. Certain fatty acids are PPARgamma ligands and can control
      adipogenesis. Moreover, some fatty acids act as signaling molecules regulating
      their differentiation into adipocytes or death. Accordingly, the lipid
      composition of the diet and PPARgamma agonists can regulate the balance between
      adipogenesis and death of adipocytes and, therefore, the obesity.

PMID- 19768250
TI  - [Importance of the dietary fat on the prevention and control of metabolic
      disturbances and cardiovascular disease].
AB  - The World Health Organization (WHO) has recently reinforced the fact that
      inadequate diets, along with physical inactivity, are among the ten main
      determinant factors of mortality. Several randomized trials demonstrated that
      dietary interventions may lower or even prevent the occurrence of several non
      communicable diseases. In this context, the role of diet has been exhaustively
      evaluated in several clinical and epidemiological studies. Thus, it is well
      established in literature that the amount and type of dietary fat have a direct
      influence on cardiovascular risk factors, such as lipids and plasma lipoprotein
      concentration, as well as their association with inflammatory processes. Fatty
      acids also participate in complex intracellular signaling systems, a function
      which has been currently investigated. Dietary polyunsaturated fatty acids (PUFA)
      act not only by altering membrane lipid composition, cellular metabolism and
      signal transduction, but also modulating gene expression by regulating the
      activity and/or production of different nuclear transcription factors. The aim of
      this article is to review important topics regarding the lipids metabolism and
      correlate them with nutritional therapies that may contribute to the prevention
      and treatment of related diseases.

PMID- 19768251
TI  - [Sodium intake and metabolic syndrome: a systematic review].
AB  - Recent studies have shown that sodium intake restrictions may increase insulin
      resistance (IR) and induce changes on serum lipoproteins and on inflammation
      markers that are similar to those found in metabolic syndrome (MS). We performed
      a systematic review of literature regarding the effects of restricting sodium
      intake on MS or on IR. Nine articles were included in the review. Restriction of
      sodium consumption was associated with increase insulin resistance in two
      articles and with decrease in three others. In seven of nine articles, salt
      intake restriction determined blood pressure reduction, and in two articles
      adverse effects on markers of MS were found. Most studies showed beneficial
      effects of moderate sodium intake restriction, associated or not to others
      nutritional modifications or increased physical activity. Further studies are
      needed to evaluate the effects of moderate sodium consumption reductions on MS
      and IR.

PMID- 19768252
TI  - [Assessment of food consumption and nutrient intake in clinical practice].
AB  - The assessment of food consumption in clinical practice is often carried out to
      develop and implement nutritional advice. Factors as the patient health
      conditions, the evolution of his/her clinical condition as well as the reasons
      that motivated the search for advice will guide the selection of the best method
      of assessment of food consumption or nutrient intake to employ. The chosen method
      might drive the professional to offer a food plan that aims to promote health, to
      prevent illness, and to alter the nutritional state of the patient. Despite the
      easily available national literature on methods and techniques to estimate food
      consumption, it is not uncommon that professionals still have doubts about what
      methods are the most appropriated in daily practice. This study aimed to present
      a critical analysis, taking into account the clinical applicability, of the food
      assessment methods and its characteristics.

PMID- 19768253
TI  - [Vitamin D and endocrine diseases].
AB  - Vitamin D insufficiency/deficiency has been worldwide reported in all age groups
      in recent years. It has been considered a Public Health matter since decreased
      levels of vitamin D has been related to several chronic diseases, as type 2
      diabetes mellitus (T2DM), obesity and hypertension. Glucose intolerance and
      insulin secretion has been observed during vitamin D deficiency, both in animals
      and humans resulting in T2DM. The supposed mechanism underlying these findings is
      presence of vitamin D receptor in several tissues and cells, including pancreatic
      beta-cells, adipocyte and muscle cells. In obese individuals, the impaired
      vitamin D endocrine system, characterized by high levels of PTH and
      1,25(OH)(2)D(3) could induce a negative feedback for the hepatic synthesis of
      25(OH)D and also contribute to a higher intracellular calcium, which in turn
      secrete less insulin and deteriorate insulin sensitivity. In hypertension,
      vitamin D could act on renin-angiotensin system and also in vascular function.
      Administration of 1,25(OH)(2)D(3) could decreases renin gene expression and
      inhibit vascular smooth muscle cell proliferation. However, prospective and
      intervention human studies that clearly demonstrates the benefits of vitamin D
      status adequacy in the prevention and treatment of endocrine metabolic diseases
      are lacking. Further research still necessary to assure the maximum benefit of
      vitamin D in such situations.

PMID- 19768254
TI  - [Role of dietary lipids in diabetic nephropathy].
AB  - The aim of the present study was to review the possible role of dietary lipids in
      diabetic nephropathy (DN), taking into account associated abnormalities of serum
      lipids and interaction of dietary and genetic aspects. Dietary lipids may have an
      important role in the development and progression of DN. The fat diet composition
      has been associated with DN, particularly with microalbuminuria, serum lipids
      abnormalities, and endothelial function. However, the beneficial effect of fat
      intake modification for these patients is not fully established, especially
      regarding hard outcomes, such as DN incidence and progression, kidney failure,
      and death. Moreover, genetic factors may influence the response of serum lipids
      to fat intake. The identification of specific genetic polymorphisms associated
      with this interaction could allow adoption of individual nutritional strategies
      in DN.

PMID- 19768255
TI  - [Effects of dietary bioactive compounds on obesity induced inflammation].
AB  - It is largely accepted the important role of food and feeding habits on health
      maintenance and development of non transmissible chronic diseases (NTCD).
      Epidemiologic evidences show that increasing vegetable consumption positively
      impacts health. On the other hand, in vivo and in vitro studies in animals show
      that non-nutrient bioactive food substances partly explain the role of food on
      the maintenance of health and on the risk reduction of these diseases. The
      modulation of gene expression of proteins that are involved in the cellular
      signaling pathways of NTCD is an important mechanism of the bioactive food
      substances, indicating their importance in disease prevention. Bioavailability,
      metabolic routes and the action of the resultant metabolites of bioactive food
      compounds are important aspects that may affect NTCD. All these aspects have
      actively been investigated in the last years and resulted in a greater
      understanding of the beginning, progression and prevention of NTCD. This review
      aimed at discussing the involved mechanisms of the inflammatory response induced
      by obesity and the role of bioactive food compounds in modulating such response.

PMID- 19768257
TI  - [Effect of caloric restriction on longevity].
AB  - Calorie restriction (CR) is the most evaluated nutritional intervention to
      increase lifespan in a variety of animal species, including human beings. CR has
      also been shown to delay the onset or reduce the incidence of many age-related
      diseases. The mechanism that could explain the effect of calorie intake on aging
      is related to the reduction of body fat and insulin signaling as well as reactive
      oxygen species produced during breathing. These phenomena cause oxidative damage
      to DNA and RNA promoting the process of aging and increasing the risk of
      illnesses. However, the effect of CR on longevity in human beings is not fully
      established and further studies are necessary in order to identify the molecular
      and cellular mechanisms for the therapeutic effect of RC. Moreover, it is
      necessary to set up the differences between the beneficial effects of caloric
      restriction from those related to dietary healthy habits.

PMID- 19768256
TI  - [Critical analysis of the American Diabetes Association dietary recommendations
      for cardiovascular disease in diabetes mellitus].
AB  - Cardiovascular disease (CVD) is the main cause of mortality among patients with
      diabetes mellitus (DM), and dietary intervention is an essential measure to
      prevent and treat this complication. The aim of this manuscript was to review
      scientific evidence that underlies the dietetic recommendations of the American
      Diabetes Association (ADA) for prevention and treatment of CVD in patients with
      DM. The ADA guidelines are mostly based on studies performed on patients with CVD
      and without DM. The evidence-based dietary recommendations for patients with DM
      are to increase the intake of fish and soluble fibers. Although DM has been
      considered as an equivalent of established CVD, the adoption of the same dietary
      recommendations for patients without DM and with CVD for all patients with DM is
      still questionable -- especially considering the peculiarities of CVD in DM.
      Randomized clinical trials including patients with DM should provide further
      information regarding the benefits of these dietary interventions for CVD.

PMID- 19768258
TI  - [Systematic review of weight loss diets: role of dietary components].
AB  - Being overweight is the sixth most important risk factor for chronic non
      transmissible diseases. Many publications have been produced in recent years to
      evaluate the best weight loss alternative. The aim of this systematic review was
      to critically assess the role of dietary components (macronutrients and/or foods)
      in weight loss diets in adults recently described in the literature. Randomized
      clinical trials, with at least one year of follow-up, were selected in MedLine
      (in Portuguese, English and Spanish languages) from 2004 to 2009. Among the 23
      studies included with different types of diets, 13 presented a rate of withdrawal
      from the study > or = 25% in at least one of the diets. In conclusion, most diets
      where the weight loss was > 5% of initial weight were energy restricted.
      Furthermore, following low carbohydrate or Mediterranean diets can be an
      alternative to isolated energy restriction, but these data are yet to be
      confirmed.

PMID- 19768259
TI  - Milk intake and the risk of type 2 diabetes mellitus, hypertension and prostate
      cancer.
AB  - Milk intake is widely recommended for a healthy diet. Recent evidences suggest
      that milk/dairy products are associated with a lower risk of type 2 diabetes and
      hypertension. On the other hand, high calcium intake has been associated with a
      higher risk of prostate cancer. The calcium and vitamin D content in dairy foods
      could have beneficial effects on glucose metabolism and renin/angiotensin system
      as well regulates body weight. The association between high dairy/calcium
      consumption and prostate cancer risk are related to the presence of estrogens and
      insulin like growth factor (IGF-I) in milk. Based on the current evidence, it is
      possible that milk/dairy products, when consumed in adequate amounts and mainly
      with reduced fat content, has a beneficial effect on the prevention of
      hypertension and diabetes. Its potential role in the pathogenesis of prostate
      cancer is not well supported and requires additional study.

PMID- 19768260
TI  - Barcoding lepidoptera: current situation and perspectives on the usefulness of a
      contentious technique.
AB  - Faced by a growing need of identification and delimitation of new and established
      cryptic species that are being lost at an increasing rate, taxonomists can now
      more than ever take advantage of an enormous variety of new molecular and
      computational tools. At this moment they should be open to all new available
      technologies in the so called 'technology-driven revolution' in systematics. The
      use of the 'DNA barcode' has been discussed by those applying successfully this
      approach to identify and diagnose species and by those who believe that the flaws
      in the use of this molecular marker are as many as to negate the worth of its
      employment. For insects of the order Lepidoptera neither side seems totally
      correct or wrong, and although many groups of lepidopterans have been
      taxonomically resolved by using exclusively or additionally this marker for
      diagnoses, for others the 'barcode' helped little to resolve taxonomic issues.
      Here we briefly present some pros and cons of using DNA barcode as a tool in
      taxonomic studies, with special attention to studies with groups of Lepidoptera
      developed in the last few years.

PMID- 19768261
TI  - Life history parameters of Trialeurodes vaporariorum (Westwood) (Hemiptera:
      Aleyrodidae) at different environmental conditions on two bean cultivars.
AB  - Life-history parameters of the greenhouse whitefly Trialeurodes vaporariorum
      (Westwood), an important pest of bean crops in Colombia, were determined in
      environmental control chambers on two dry bean (Phaseolus vulgaris) cultivars
      (cv.). Trialeurodes vaporariorum longevity on cv. Chocho decreased as temperature
      increased from 22.6 d at 19 degrees C to 5.9 d at 26 degrees C. Fecundity was
      significantly lower at 19 degrees C (8.6 eggs/female), as compared to 22 degrees
      C (32.6 eggs/female) and 26 degrees C (33.3 eggs/female) on cv. Chocho. Fecundity
      on cv. ICA-Pijao was much higher (127.2 eggs/female) than on cv. Chocho (32.6
      eggs/female) at 19 degrees C. The intrinsic rate of population increase (r m) was
      highest at 22 degrees C (0.061), intermediate at 19 degrees C (0.044) and lowest
      at 26 degrees C (0.035) on cv. Chocho, and was 0.072 on cv. ICA-Pijao at 19
      degrees C. Life history parameters of T. vaporariorum are compared to those of
      one of its natural enemies, the parasitoid Amitus fuscipennis MacGown & Nebeker.
      Finally, data are presented on the distribution of the parasitoid related to the
      altitude for the Valle del Cauca, Colombia.

PMID- 19768262
TI  - [Occurrence and performance of Euschistus heros (F.) (Heteroptera: Pentatomidae)
      on alternative host plants in Rio Grande do Sul State, Brazil].
AB  - The Neotropical brown stink bug Euschistus heros (F.) can reach high densities in
      some soybean areas in Brazil. Besides soybean, it also feeds on other plants, but
      little is known on the alternative hosts of E. heros in Rio Grande do Sul state.
      In this study, wild non-cultivated hosts of E. heros at Norwest of Rio Grande do
      Sul state were determined, and the E. heros performance was compared when fed on
      soybean and on wild hosts. Bugs were sought in plants located inside and on the
      edge of soybean fields during 2004/2005 and 2005/2006 seasons. Adults were
      recorded feeding on seeds of Amaranthus retroflexus (Amaranthaceae), and on
      fruits of three Solanaceae, mainly Vassobia breviflora. Immature survivorship on
      soybean (86.7%) and on V. breviflora (81.8%) was the same, but nymphs fed on A.
      retroflexus did not reach adulthood. The host plant used during immature
      development greatly affected adult weight, with V. breviflora yielding the
      heaviest adults; however, adult survivorship and longevity when fed on different
      host plants were the same. Females fed on soybean laid larger egg masses than
      those fed on V. breviflora , but the overall fecundity was not affected.

PMID- 19768263
TI  - Chironomidae assemblage structure in relation to organic enrichment of an aquatic
      environment.
AB  - In this study we determined the taxonomic diversity of larval Chironomidae
      upstream and downstream to discharges of the sewage treatment plant (STP) from
      Agro-industrial District of Anapolis, State of Goias, Brazil. Additionally, we
      evaluated the use of the lognormal distribution as a measure of biotic integrity
      of this system. The Chironomidae communities were sampled in three sites,
      upstream and downstream of the discharge of the sewage treatment plant (STP). We
      fitted the truncate lognormal distribution based on a nonlinear regression of the
      datasets using least squares as loss function in an iterative quasi-Newton
      procedure. The total of 21,498 individuals were sampled, from 24 Chironomidae
      genera, Chironomus, Polypedilum, Rheotanytarsus e Thienemanniella, with 73.9%,
      14.4%, 7.1% and 4.5%, respectively, of all analyzed community; they are generally
      considered resistant to organic pollution. The assemblage of the site upstream
      was described for a truncate lognormal distribution. The extreme increase in
      abundance of some genera in the first site downstream produced a distribution not
      fitted to lognormal. The second site downstream however, permits a good fit to
      lognormal, probably due to the decrease in abundance of the dominant groups.
      These data substantiate the hypothesis that Chironomidae community is not
      suitably characterized by lognormal distribution at disturbed environments.
      Consequently, these aquatic communities were ecological disordered by organic
      pollution which caused the lost of sensible species and the dominance of those
      tolerants to this sort of impact. Additionally, the study highlighted the
      distribution lognormal approach as a valuable method to assess environmental
      impacts.

PMID- 19768264
TI  - Life cycle of Goeldichironomus holoprasinus goeldi (Diptera: Chironomidae) in
      laboratory.
AB  - The larvae of Chironomidae are very important due to their density and role in
      aquatic food webs. Goeldichironomus holoprasinus Goeldi is one of the most
      abundant species of Chironomidae in man-made and natural systems, being widely
      used in water quality assessments. Because of its tolerance to stressing
      environmental factors, many studies have investigated the effects of stressors on
      G. holoprasinus anatomy and bionomic attributes. The main aim of this work was to
      describe G. holoprasinus life cycle attributes in laboratory conditions. The
      cephalic capsule growth among instars was 1.64 in average (Dyar proportion),
      whereas the total size growth was continuous. The average room temperature
      registered was 26 degrees C (18-33 degrees C). In this conditions the D value
      (time from oviposition to first imago emergence) was 13 days, whereas the minimum
      G value (interval from the oviposition to the first progeny of the next
      generation) was 16 days. The emergence lasted four days, which determined that
      average G of 18 days. Thus, at registered temperatures G. holoprasinus has a
      short life cycle.

PMID- 19768265
TI  - An improved bait method for collecting Hymenoptera, especially social wasps
      (Vespidae: Polistinae).
AB  - In this work, an alternative method for the capture of neotropical social wasps
      is described, which may supplement or replace the procedures commonly used in
      wasp surveys. The method was tested in a seasonal semideciduous forest in the
      northwest of Sao Paulo State, collecting a larger number of species and a greater
      abundance of social wasps and of other Hymenoptera than other methods also used
      in the same area, namely Malaise traps, bottle traps and meat baits. The proposed
      method was adapted from Wille (1962) who used an attractive solution based on
      water and honey for bee attraction. In here, the attractive solution was based on
      water, salt and crystal sugar, and was effective in attracting bees and solitary
      wasps, but mainly social wasps, which is the group of interest for this report.

PMID- 19768266
TI  - [Microarthropods from the altiplanic andean steppe, with focus on oribatid
      species (Oribatida: Acarina)].
AB  - In soils under seven types of high altitude, native vegetation and one plantation
      in the northernmost Chilean Altiplanic region, 20 microarthropod orders or
      suborders were found, including 21 oribatid mite species. Seven of these species
      are first mentioned for Chile. No oribatid mites were found in soils far from
      vegetation. Data are given as average densities (n masculine ind./1000 ml),
      accounting for plant preference, geographical distribution and updated taxonomic
      status for each species. Ten oribatid species form a group of Andean altiplanic
      steppe fauna also found in Peru and Bolivia. Other three species have been also
      found in different austral ecosystems in Argentina, and a group of eight species
      seems to be cosmopolitan.

PMID- 19768267
TI  - Description of the third-instar of Anastrepha leptozona Hendel (Diptera:
      Tephritidae).
AB  - The morphology of the third-instar larva of Anastrepha leptozona Hendel is
      characterized using optical and scanning electron microscopy. The
      antennomaxillary complex, oral ridges, labium, stomal sensory organ,
      cephalopharyngeal skeleton, anterior and posterior spiracles and caudal segment
      are described and illustrated. Mature larvae of A. leptozona present a 'ventral
      sclerite' below the pharyngeal sclerite which is characterized for the first time
      in Anastrepha species.

PMID- 19768268
TI  - A new species of Acanthoscelides Schilsky (Coleoptera: Bruchidae) from Mexico
      with some biological notes.
AB  - A new species of Acanthoscelides collected in Chiapas, Mexico is described and
      figured. Rhynchosia precatoria is cited as a new host plant record for A. dani
      sp.n and A. flavescens Fahraeus. The braconid Heterospilus prosopidis Viereck was
      found as parasitoid of both species of bruchids.

PMID- 19768269
TI  - Chewing lice of the genus Myrsidea waterston (Phthiraptera: Menoponidae) from the
      emberizidae and thraupidae (Passeriformes) in Mato Grosso do Sul, Brazil.
AB  - This paper presents the first record of three chewing lice species of the genus
      Myrsidea collected from one emberizid and two thraupid hosts in Mato Grosso do
      Sul, Brazil. Morphological characters of M. seminuda are added for the last
      redescription of this species and a new key to males of 'bonariensis species
      group' is presented.

PMID- 19768270
TI  - A new species of Brueelia Keler (Phthiraptera: Philopteridae) parasitic on the
      Common Diuca-Finch, Diuca diuca diuca (Aves: Emberizidae) in Chile.
AB  - A new species of the genus Brueelia Keler is described as parasitic on the Common
      Diuca-Finch, Diuca diuca diuca, based on specimens from three localities in
      Chile: Punitaqui (Coquimbo Province), La Rinconada (Colchagua Province) and
      Chillan (Nuble Province). The species is fully described and illustrated, and
      brief comments on its morphological affinities with allied species are also made.

PMID- 19768271
TI  - Description of the Aguatala compsa young (Hemiptera: Cicadellidae: Cicadellinae)
      female.
AB  - The female of Aguatala compsa Young is for the first time described and
      illustrated based on specimens from Colombia. This consists also on a new
      distribution record for the monotypic genus Aguatala Young. The female genitalia
      of A. compsa are described in detail and compared with those of supposedly
      related genera belonging to the Erythrogonia generic group (sensu Young).

PMID- 19768272
TI  - [Effect of age, photoperiod and host availability on the parasitism behavior of
      Oomyzus sokolowskii Kurdjumov (Hymenoptera: Eulophidae)].
AB  - The high reproduction rate, potential to cause damage, wide geographic
      distribution and resistance to insecticides of Plutella xylostella (L.) makes
      difficult its efficient control. However, larvae and pupae of this pest are
      naturally parasitized by Oomyzus sokolowskii (Kurdjumov), providing opportunities
      to improve the natural parasitism. This study investigated the effects of the age
      of adult parasitoids, host availability and time of exposure on O. sokolowskii
      parasitism behavior. The number of larvae encounters by parasitoid females and
      the parasitism rate increased with parasitoid age up to 96h. The parasitization
      was higher when wasps received a constant number of hosts daily in comparison
      with a random number (13.3 versus 8.9 larvae parasitized). Female parasitization
      activity was maintained up to the age of 20 days in both treatments and exhibited
      similar longevity (constant host = 33.5 d; and random host = 34.7 d). The progeny
      produced per female and the number of parasitoids emerged per host significantly
      decreased as wasps aged. There was no significant effect of the light regime (12h
      darkness or 12h light exposure) on the parasitization, although parasitoid was
      more active after 3h of light exposure. Therefore, further studies on field
      application of O. sokolowskii should consider the release of 48 h- to 72 h-old
      parasitoids at dawn as a way to increase the success of host parasitization.

PMID- 19768273
TI  - [Potential of Metarhizium anisopliae and Beauveria bassiana isolates and neem oil
      to control the Aphid Lipaphis erysimi (Kalt.) (Hemiptera: Aphididae)].
AB  - This work aimed to determine the efficiency of the entomopathogenic fungi
      Metarhizium anisopliae and Beauveria bassiana to control the aphid Lipaphis
      erysimi (Kalt.) (Hemiptera: Aphididae) in kale Brassica oleracea var acephala
      D.C., as well as their compatibility with a neem oil formulation (Neemseto). Ten
      isolates of both fungi were tested and the most pathogenic ones were B. bassiana
      CG001 and M. anisopliae CG30 with 90% and 4.4 days, and 64% and 3.8 days of
      mortality and median lethal time, respectively. Bioassays with neem at
      concentrations of 0.5, 1.0 and 2.0% were done either by leaf discs dipping or
      spraying the aphids on the leaf discs. The neem spraying treatment at 2.0%
      provided 90% mortality. The use of B. bassiana isolate CG001 or M. anisopliae
      isolate CG30 with neem at 0.125, 0.25, and 0.5%, demonstrated that these isolates
      could have their spore viability or colony growth affected when exposed to neem
      concentrations higher than 0.25%. In absolute values, the isolates B. bassiana
      CG001 and M. anisopliae CG30 are the most virulent to L. erysimi, and could be
      utilized in the management of this pest.

PMID- 19768274
TI  - [Resistance of squash genotypes to Bemisia tabaci (Genn.) biotype B (Hemiptera:
      Aleyrodidae)].
AB  - Field assays were performed to evaluate the attractiveness and the non-preference
      of whitefly Bemisia tabaci (Genn.) biotype B for oviposition on squash genotypes
      (Cucurbita pepo) and to observe the susceptibility of genotypes (Novita, Sandy,
      Caserta Cac Melhorada, Novita Plus, Samira, Bianca, AF-2858 and Caserta TS) to
      silverleaf symptoms. The Sandy genotype was the least attractive to whitefly,
      while Novita Plus, AF-2858 and Samira were the most attractive. The Caserta Cac
      Melhorada genotype was the least preferred for oviposition. The Sandy and AF-2858
      genotypes were the most productive, with the highest mean of fruits produced. The
      lowest silverleaf symptoms index was observed for the Sandy and Caserta Cac
      Melhorada genotypes.

PMID- 19768276
TI  - Microbiota associated with tramp ants in a Brazilian University Hospital.
AB  - Our aim was to study the fauna of ants in the Hospital Universitario of the
      Universidade Federal do Triangulo Mineiro, municipality of Uberaba, Minas Gerais
      State, Brazil, as well as to identify the microorganisms the ants carry and their
      patterns of resistance to antibiotics. Sterile tubes (traps) containing honey
      were used to attract the ants. Traps were exposed for 3h, and those which
      attracted ants were considered the test group, while the ones that did not
      attract the insects constituted the control group. Only the ant species Tapinoma
      melanocephalum (Fabricius) was sampled. Sixty microorganisms were isolated from
      the sampled ants, including seven Gram-positive bacilli, 14 Gram-negative
      bacilli, 22 Gram-positive cocci and 17 filamentous fungi. Pseudomonas,
      Staphylococcus and Group D Streptococcus were the microorganisms with the highest
      resistance to the tested antibiotics. The ants should be considered an important
      vector of infections as they carry several pathogenic microorganisms, spreading
      them on the surface of sterile materials, equipment and uncontaminated food. It
      is impossible to define the exact role of ants in nosocomial infections at this
      moment; however, this issue must be better studied and special attention must be
      given by the commissions of Nosocomial Infection Control.

PMID- 19768275
TI  - Control of silverleaf whitefly, cotton aphid and kanzawa spider mite with oil and
      extracts from seeds of sugar apple.
AB  - Development of alternative methods for pest management is needed with the
      increased concern for adverse effects of pesticides for human health and the
      environment. The main goal of our study was to test the oil from seeds of sugar
      apple (Annona squamosa), an edible tropical fruit for pest control. The oil
      pressed out of seeds was as effective in controlling the silverleaf whitefly,
      Bemisia argentifolii Bellows & Perring (Homoptera: Aleyrodidae), infesting leaves
      of tomato plants in greenhouse conditions as the recommended insecticide, with
      the advantage of not being phytotoxic. When observed with a scanning electron
      microscope, the seed oil caused whitefly nymphs to shrink and detach from the
      leaf surface. Sugar apple seed oil was also very effective in controlling the
      cotton aphid, Aphis gossypii Glover (Homoptera: Aphididae), on melon leaves and
      the Kanzawa spider mite, Tetranychus kanzawai Kishida (Acari: Tetranychidae), on
      soybean leaves. The study revealed the possibility of developing the oil from
      sugar apple seeds, an agricultural waste, into a broad spectrum product friendly
      to the environment and human health for crop pest management.

PMID- 19768277
TI  - [Genetic variability in Aedes aegypti (L.) (Diptera: Culicidae) populations using
      RAPD markers].
AB  - Aedes aegypti (L.) is an important vector of diseases such as the yellow fever
      and dengue, present in tropical and subtropical regions. The objective of this
      study was to analyze the genetic variability of different A. aegypti populations
      using RAPD (Random Amplified Polymorphic DNA) markers as a basic study to support
      the use of biocontrol strategies. DNA of ten collected larvae from three
      different populations were analyzed using ten RAPD primers. The results indicated
      the existence of genetic variability inter and intrapopulation. This was
      confirmed by a dendrogram that grouped the populations in two main clusters with
      a genetic similarity of 24%. In one of these clusters, it was possible to
      distinguish two populations that showed 50% similarity. The molecular variance
      analysis indicated that the interpopulation genetic diversity (55,01%) was higher
      than the intrapopulation genetic diversity (44,99%). A high genetic polymorphism
      (Ht = 0.2656) and high levels of genetic differentiation between populations (Gst
      = 0.3689) were found. The adopted DNA extraction protocol proved to be efficient
      regardless the insect development stage used, avoiding the addition of reagents
      or additional stages of processing. Future experiments can be performed to
      confirm if the detected variability is related to the resistance characteristics
      of each population to a determined pesticide.

PMID- 19768278
TI  - [Insect pests dissemination by extruded starch packages].
AB  - We observed the viability of extruded starch products used as impact protector
      for fragile packing as a food source of the following stored grains pests:
      Cryptolestes ferrugineus (Stephens), Lasioderma serricorne (Fabr.), Oryzaephilus
      surinamensis (L.), Sitophilus oryzae (L.), Tribolium castaneum (Herbst)
      (Coleoptera) and Plodia interpunctella (Hubner) (Lepidoptera). Cryptolestes
      ferrugineus, L. serricorne and T. castaneum were found in these products, which
      are used by them as shelter and food. Under experimentation, we observed the
      development of O. surinamensis, S. oryzae and P. interpunctella feeding on this
      food source. Thus, it is recorded the viability of such material to be a
      potential dispersal vehicle to spread insect pests.

PMID- 19768279
TI  - First host record for Winthemia analis (Macquart) (Diptera: Tachinidae:
      Exoristinae) in Brazil: Brassolis sophorae laurentii Stichel (Lepidoptera:
      Nymphalidae: Brassolinae).
AB  - Hymenopteran and dipteran endoparasitoids are reported acting as pupae
      endoparasitoids of Brassolis sophorae (L.). Concerning the scientific and
      economic importance of these interspecific relationship, and aiming to increase
      the knowledge related to natural and conservative biological control, the present
      study records Winthemia analis (Macquart) as larval-pupal parasitoid of Brassolis
      sophorae laurentii Stichel in the State of Alagoas, Brazil. This report presents
      some data on the bioecology of this parasitoid, on its distributional range in
      Brazil and a host species for the first time.

PMID- 19768280
TI  - [Culicidae (Diptera) in the dam area bordering the states of Santa Catarina and
      Rio Grande do Sul, Brazil].
AB  - The Culicidae composition of the Barra Grande Lake situated between the
      municipalities of Esmeralda (Rio Grande do Sul State) and Anita Garibaldi (Santa
      Catarina State) was assessed by monthly samplings. Twenty-four species were
      identified from a total of 1,185 specimens (74.7% as adults and 25.3% as
      immatures), with Aedes fluviatilis Lutz as the most frequent species. Several
      species are new records, and some of them are of public health interest. It is
      suggested that local environmental changes may alter the relationship between
      humans and vector mosquitoes.

PMID- 19768281
TI  - [Two new populations of Lutzomyia pseudolongipalpis Arrivillaga & Feliciangeli
      (Diptera: Phlebotominae) vector of visceral leishmaniasis in Venezuela].
AB  - Two new populations of Lutzomyia pseudolongipalpis Arrivillaga & Feliciangeli,
      species belonging to the Lutzomyia longipalpis (Lutz & Neiva) complex, are
      reported in Venezuela on diagnostic isoenzymes.

PMID- 19768282
TI  - A new sterile technique effective on capturing tramp ants for microbiological
      investigations.
AB  - Tramp ants are an outstanding group of organisms that have a definitive and
      important role in carrying pathogens. The purpose of this study was to develop a
      microbiological sterile technique of collecting ants from contaminated areas. The
      traps were composed of Petri dishes containing culture media, and were tested to
      verify the applicability of the system. A positive correlation between the
      microorganism growth and the presence of ants inside or around traps was
      observed. The technique described demonstrated to be useful to collect ants from
      different environments, helping the surveillance of pathogenic microorganisms
      that are of public health concern.

PMID- 19768285
TI  - The troubled heparin issue in the Brazilian market and the search for solutions.

PMID- 19768287
TI  - The magic sextet of clinical research.
AB  - This article approaches some general guidelines for evaluating clinical research
      (design, execution and reporting), including the initial research 'idea' (or
      question to be answered), 'hypothesis and objective' which should be aligned with
      the 'primary variable' to be investigated and the 'conclusions' reached on the
      basis of the results of the study. One cannot forget that the study 'title'
      should reflect the 'idea' and relative 'objective' of the study and the
      'conclusion', emphasizing the 'Magic Sextet of Research'.

PMID- 19768288
TI  - Results of the establishment of an organizational model in a cardiovascular
      surgery service.
AB  - OBJECTIVE: Increasing complexity of patients referred to cardiac surgery demands
      more effective heart centers, in order to maintain the same quality. The aim of
      this study is to examine the short-term effect of adoption of an organizational
      model on surgical outcomes. METHODS: From January 2006 to June 2007, 367
      consecutive adult patients underwent cardiovascular surgery. Pre-, intra- and
      postoperative data were prospectively collected and transferred to an
      institutional database. Organizational model was established in August 2006, and
      based on integrated multiprofessional team work patient-centered, evidence-based
      medicine with standardized patient care and personal conflict management. The
      outcomes studied were hospital mortality and combined adverse events (death,
      stroke, acute myocardial infarction and acute renal failure), by using
      multivariate logistic regression analysis. RESULTS: After establishment of such
      model, there was reduction of hospital mortality (from 12% to 3.6%, relative
      risk= 0.3; P=0.003) and combined events (from 22% to 15%, relative risk=0.68;
      P=0.11). Operations performed previously to the model were independently
      associated with higher mortality (OR=2.5; P=0.04), adjusted to preoperative
      characteristics and Euroscore risk stratification system. Other predictors of
      mortality were age > 65 years (OR=6.36; 95%CI 2.57 - 17.21; P<0.0001) and
      cardiopulmonary bypass time > 145 minutes (OR=8.57; 95%CI 3.55 - 21.99;
      P<0.0001). CONCLUSION: Marked improvements in surgical outcomes depend on
      development of cardiac surgery centers based on organizational models similar to
      the model proposed in this study.

PMID- 19768289
TI  - Uncovered stent does not provoke reactions in renal arteries and renal parenchyma
      in swines.
AB  - OBJECTIVE: To assess the histological changes of the aorta, the renal arteries
      and the renal parenchyma in swine, induced by a metalic uncovered stent implanted
      in transrenal position in the abdominal aorta. METHODS: Ten pigs with a mean
      weight of 86.6 kg and mean age of 6 months underwent implantation of metal stent
      graft placed in the aorta at the level of the renal arteries after 100 days of
      implantation. The self-expanding stents were released by laparotomy. Anatomic and
      histological analyses of the abdominal aorta, the renal arteries and the renal
      parenchyma were performed. Histological slices were performed in the following
      sites: 1) transitional zone between the aorta with and without stent graft; 2)
      portion of the renal arteries ostia; 3) renal parenchyma. The slices were stained
      through the hematoxylin and eosin stain technique and analyzed according the
      protocol of histological analyses applied in the clinical practice of pathology
      labs. RESULTS: The macroscopic findings showed thickening of the aortic wall;
      patent renal arteries; and normal anatomic renal structures. Microscopic
      analyses, close to the stents, showed thickening of the vascular wall, renal
      arteries without changes, and preserved renal parenchyma. CONCLUSION: The
      uncovered stainless steel stent caused a significant inflammatory reaction with
      thickening of the aortic wall. However, the renal arteries remained patent and
      the renal parenchyma did not present embolic or ischemic changes.

PMID- 19768290
TI  - Surgical treatment of partial anomalous pulmonary venous connection to the
      superior vena cava.
AB  - OBJECTIVE: Surgical treatment of anomalous pulmonary venous connection to the
      superior vena cava, associated with sinus venous atrial septal defect, is well
      established and correlates with low mortality and morbidity. In order to reduce
      the incidence of stenosis or occlusion of the right superior vena cava,
      especially when associated with the presence of left superior vena cava, the
      right atrial appendage was used to enlarge the right superior vena cava, after
      the diversion of the anomalous pulmonary veins for the left atrium. METHODS:
      Between June 1986 and September 2008, 95 consecutive patients were operated with
      anomalous drainage in the superior right vena cava and high right atrium. Ages
      ranged from 6 months to 68 years and females predominated with 50 cases. RESULTS:
      There was no death in the immediate or late post operative care. The sinus
      cardiac rhythm was preserved in all cases and there was no complications in the
      late follow up. CONCLUSION: This paper demonstrates the applicability of the
      technique described, with favorable results on mortality, rhythm disturbances and
      complications in the right superior vena cava.

PMID- 19768291
TI  - CABG late angiographic grafting patency analysis in patients with recurrent
      symptoms.
AB  - OBJECTIVE: Left internal thoracic artery (LITA) grafting has become the gold
      standard in coronary artery bypass graft procedure (CABG). In order to optimize
      the use of LITA or other grats, sequential anastomosis has been used. There is no
      consensus on equivalence of results between isolated and sequential grafts. The
      aim of this study is to compare the patency of isolated versus sequential grafts.
      METHODS: From January 2000 to August 2007, a retrospective patency analysis of
      the grafts used in 88 symptomatic patients who underwent CABG procedure in our
      Service was performed through cinecoronariography. Statistical analysis was
      performed through Student's t test. Each distal anastomosis was considered an
      independent graft. RESULTS: The mean postoperative period was of 53 +/- 138
      months and mean age was 64 +/- 11 years. LITA isolated grafts presented patency
      rate significantly higher than the sequential grafts, respectively 92% (46/50)
      and 77% (30/39) P = 0.02. However, in injured coronary arteries of >or= 70%,
      isolated LITA patency rate was similar to sequential grafts, (95%; 37/39) and
      (93%; 26/28) respectively; P = 0.37. Mean radial artery patency rate was similar
      to isolated 71% (5/7) and sequential 90% (19/21) grafts; P = 0.10. Saphenous vein
      patency rates were similar for isolated 72% (31/43) and sequential 81% (73/90)
      grafts; P = 0.12. There was no difference between radial artery and saphenous
      vein patency rates. CONCLUSION: In symptomatic patients, isolated LITA patency is
      superior than sequential LITA. However, in coronary injuries of >or= 70%, the
      isolated and sequential patency rates are similar. Sequential grafts from radial
      artery and saphenous vein are similar to their respective isolated grafts.

PMID- 19768293
TI  - Evaluation of ischemic postconditioning effect on mesenteric ischemia treatment:
      experimental study in rats.
AB  - OBJECTIVE: To assess the preconditioning and postconditioning effect on
      intestinal mucosal lesions in rats undergone mesenteric ischemia and reperfusion
      procedure. METHODS: Thirty Wistar rats were studied and divided into three
      groups: Group A, 10 rats undergone mesenteric ischemia (30 minutes) and
      reperfusion (60 minutes); Group B, 10 rats undergone mesenteric ischemia and
      reperfusion preceded by ischemic preconditioning for three cycles of ischemia and
      reperfusion for two minutes each; Group C, 10 rats undergone mesenteric ischemia
      and reperfusion and, preceding the beginning of reperfusion, ischemic
      postconditioning was performed for three cycles of reperfusion and ischemia for
      two minutes each. Then, a segment of small intestine was resected for
      histological analysis. We assessed the results by Chiu et al. score and the
      statistical analysis was performed. RESULTS: According to Chiu et al. score, the
      means of lesion degree were: In the group A, 3.5; Group B, 1.2; Group C, 1. The
      difference between group A with the groups B and C was considered statistically
      significant (P < 0.05). CONCLUSION: Ischemic pre- and postconditioning were
      capable of minimizing - in a similar intensity - the tissue injury on the
      intestinal mucosa of rats undergone mesenteric ischemia and reperfusion process.

PMID- 19768292
TI  - Effects of therapeutic angiogenesis with plasmid VEGF165 on ventricular function
      in a canine model of chronic myocardial infarction.
AB  - OBJECTIVE: Therapeutic angiogenesis is currently under investigation in ischemic
      heart disease. We examined the effect on left ventricular function induced by
      therapeutic angiogenesis by intramyocardial injection of plasmid VEGF(165), in a
      canine model of chronic myocardial infarction. METHODS: Left thoracotomy was
      performed in 10 mongrel dogs, and myocardial infarction induced by ligation of
      the major diagonal coronary artery. At 7 postoperative (p.o.) day (pre
      treatment), left ventricular ejection fraction was assessed by echocardiogram,
      and a second procedure was done: saline or plasmid VEGF(165) at 200 mg/mL was
      injected over 10 points of the ischemic areas of control or treated groups,
      respectively. Fourteen days later (post-treatment, day 21) a control
      echocardiogram was performed, the animals were sacrificed and histological
      examination was performed. RESULTS: Ejection fraction was maintained in the
      treated group: 52.45 +/- 15.1% on day 7 and 48.53 +/-11.74% on day 21 (P=0.59),
      and tended to decrease in the control group, from 59.3 +/- 4% to 39.37 +/- 19.43%
      (P=0.04), although absolute values did not differ significantly between groups.
      Histological examination revealed a non significant increase in capillary vessels
      number in all areas in treated group. Paradoxically, arterioles were
      significantly less in number in all areas of treated dogs. CONCLUSION:
      Intramyocardial injection of plasmid VEGF(165), in this canine model of chronic
      myocardial infarction, resulted in preservation of left ventricular ejection
      fraction, contrary to the control group where left ventricular ejection fraction
      showed continuous decline during the experiment. Histological examination,
      however, was unable to explain completely these results.

PMID- 19768294
TI  - Should the diabetics have the internal thoracic artery skeletonized? Assessment
      of sternal perfusion by scintillography.
AB  - OBJECTIVE: To assess, by scintillography, the effect of using bilateral internal
      thoracic arteries (BITAs) - prepared by two different techniques - on the sternal
      perfusion. METHODS: 35 patients undergone coronary artery bypass grafting (CABG)
      were divided into two groups: Group A (18) had both ITA's dissected using
      skeletonization technique and group B (17) as pedicle preparation. There was no
      difference in the two groups relating gender, age and demographic
      characteristics. On the 7th postoperative day the patients underwent bone
      scintillography. The statistical analysis was performed using the Student's t
      test with 95% significance. RESULTS: Group A (skeletonized ITA) showed higher
      perfusion (11.5%) of the sternum as a mean, than Group B (pedicled ITA) patients;
      however this was not statistically significant (P = 0.127). On the other hand,
      comparing the diabetic population, seven in each group, there was a marked 47.4%
      higher perfusion of the sternum in Group A patients (skeletonized ITA) comparing
      to Group B (pedicled ITA) and this difference reached statistical significance (P
      = 0.004). CONCLUSION: 1- Sternal perfusion is not affected significantly apart
      from the dissection technique used for both internal thoracic arteries in the
      general population when assessed by bone scintillography. 2 - In the diabetic
      subgroup, a significant preservation of the sternal perfusion was observed in
      patients undergone skeletonized dissection of the internal thoracic arteries.
      Although these findings should be confirmed in a greater number of cases,
      diabetic patients should have the internal thoracic arteries dissected using
      skeletonization techinque.

PMID- 19768295
TI  - Comparison between deep breathing exercises and incentive spirometry after CABG
      surgery.
AB  - OBJECTIVE: To compare the effects of deep breathing exercises (DBE) and the flow
      oriented incentive spirometry (IS) in patients undergone coronary artery bypass
      grafting (CABG) through the following variables: forced vital capacity - FVC,
      forced expiratory volume in 1 second - FEV(1), maximal respiratory pressures and
      oxygen saturation. METHODS: Thirty six patients in CABG postoperative period
      underwent thirty minutes of non-invasive ventilation during the first 24 hours
      after extubation and were randomly shared into two groups as following: DBE
      (n=18) and IS (n=18). The spirometric variables were assessed on the preoperative
      period and seventh postoperative day (POD). The respiratory muscle strength and
      oxygen saturation were assessed on the preoperative period, first, second and
      seventh POD. RESULTS: The groups were considered homogeneous in relation to the
      demographic and surgical variables. It has been noted fall in the values of FVC
      and FEV(1) between the preoperative period and the seventh POD, but without
      significant differences between groups. The maximal respiratory pressures showed
      drop in the first POD but with and partial recovery until the seventh POD, also
      without significant differences between groups. The oxygen saturation was the
      only variable that was completely recovered on the seventh POD, also without
      significant differences between groups. CONCLUSION: There were not observed
      significant differences in maximal respiratory pressures, spirometric variables
      and oxygen saturation in patients undergone deep breathing exercises and flow
      oriented incentive spirometry after coronary artery bypass grafting.

PMID- 19768296
TI  - Fluoxetine effects on mitochondrial ultrastructure of right ventricle in rats
      exposed to cold stress.
AB  - OBJECTIVE: To assess fluoxetine effects on mitochondrial structure of the right
      ventricle in rats exposed to cold stress. METHODS: The experimental study
      procedures were performed in 250-300g male EPM-Wistar rats. Rats (n=40) were
      divided into four groups: 1) Control group (CON); 2) Fluoxetine (FLU); 3) Induced
      hypothermia (IH) and; 4) Induced hypothermia treated with fluoxetine (IHF).
      Animals of FLU group were treated by the administration of gavages containing
      0.75 mg/kg/day fluoxetine during 40 days. The induced hypothermia was obtained by
      maintaining the groups 3 and 4 in a freezer at -8 degrees C for 4 hours. The
      animals were sacrificed and fragments of the right ventricle (RV) were removed
      and processed prior to performing electron microscopic analysis. RESULTS: The
      ultrastructural changes in cardiomyocytes were quantified through the number of
      mitochondrial cristae pattern (cristolysis). The CON (3.85%), FLU (4.47%) and IHF
      (8.4%) groups showed a normal cellular structure aspect with preserved
      cardiomyocytes cytoarchitecture and continuous sarcoplasmic membrane integrity.
      On the other hand, the IH (34.4%) group showed mitochondrial edema and lysis in
      cristae. CONCLUSION: The ultrastructural analysis revealed that fluoxetine
      strongly prevents mitochondrial cristolysis in rat heart, suggesting a protector
      effect under cold stress condition.

PMID- 19768298
TI  - Analysis of the hydrodynamic profile in different roller pumps models used in
      cardiopulmonary bypass.
AB  - OBJECTIVE: Among the equipments used in cardiopulmonary bypass the roller pumps
      have great importance with various models available from several manufacturers.
      The calibration is an important factor in hemolysis rates and its potential is
      different in each. Researchers do not always approach details on the pump bed
      profiles assuming that the standardized calibration settings ensure equal and
      comparable values for all models of roller pumps. We have mainly two methods for
      calibration of pumps which also interferes on the hemolytic potential. In both of
      them, the characteristics of fluid impulsion defined by the pump bed design are
      not considered. The aim of this study is to compare the hydrodynamic profile of
      three models of roller pumps available in the Brazilian market. METHOD: The
      rollers occlusion was performed by measures of drop and dynamic calibration. Two
      different silicone diameter tubes were used (3/8 x 1/16 and 1/2 x 3/32 inches).
      RESULTS: The profiles showed differences in their variances, P<0.01 for drop rate
      measures and P<0.0001 for dynamic calibration. Different changes in pressure were
      found between the pumps analyzed (P<0.002). CONCLUSION: The measures of occlusion
      are dependent on the design of the pump bed and comparisons involving roller
      pumps should be performed with caution. Blood tests should be performed to verify
      the influence of changes in hemolysis pressure.

PMID- 19768297
TI  - Ventilatory profile of patients undergoing CABG surgery.
AB  - OBJECTIVE: To assess the ventilatory, radiological and clinical profile of
      patients undergoing elective CABG in a cardiology reference hospital in South
      Brazil. METHODS: This study included 108 patients undergoing elective CABG
      surgery, in the period between April 2006 and February 2007 at the Cardiology
      Institute of Rio Grande do Sul (IC-FUC). The surgical procedure involved median
      sternotomy, and the saphenous vein and/or internal mammary artery were used for
      grafting. Lung volume and capacity, as well as the possible existence of
      ventilatory changes, were assessed by spirometry, and the ventilatory muscle
      strength was assessed using a vaccum manometer. All evaluations were performed on
      the preoperative period and on the sixth postoperative day. RESULTS: Preoperative
      levels of FEV1 and FVC were significantly reduced on the 6th postoperative day
      (P<0.001) when compared to the preoperative levels. A significant decrease of
      ventilatory muscle strength, expressed as maximum inspiratory and expiratory
      pressures (MIP and MEP), was also observed from the pre- to the sixth
      postoperative day (P<0.001). Pulmonary events were more frequent on the 6th
      postoperative day (78%) than on the 1st postoperative day (40%). CONCLUSION:
      Patients undergone CABG surgery present important reduction in pulmonary volume
      and capacity, as well as on the ventilatory muscle strength during the
      postoperative period.

PMID- 19768299
TI  - Reduction aortoplasty with external wrapping associated with aortic valve
      replacement in high-risk patients.
AB  - OBJECTIVE: To assess the midterm follow-up of reduction aortoplasty with external
      wrapping associated with aortic valve replacement in high risk patients. METHODS:
      Six patients with ascending aortic aneurysm and aortic valve disease were
      included in this study. Four of them were male. The age ranged from 61 to 70
      years (mean 65.7 years). One patient presented severe mitral valve insufficiency.
      All patients underwent aortic valve replacement (83.3% with aortic insufficiency
      and 16.7% with aortic stenosis). The inclusion criteria were: surgical aortic
      valve disease, ascending aortic aneurysm > 5.5 cm, EuroSCORE > 6 and age above 60
      years. The ascending aortic diameter ranged from 57 to 68 mm (mean 63.7 mm). Data
      were analyzed by paired T test for comparison between the studied variables and P
      < 0.05 was considered significant. RESULTS: All patients underwent reduction
      aortoplasty with external wrapping associated with aortic valve replacement. The
      postoperative hospital mortality and morbidity was 0% and 16.7% (atrial
      fibrillation), respectively. The mean ascending aortic diameter was 37.0 +/-
      4.5mm after 6 months of follow-up (P < 0.0001, compared with the preoperative
      period). The actuarial survival curve after 28 months of follow-up was 100%.
      CONCLUSION: Reduction ascending aortoplasty with external wrapping associated
      with aortic valve replacement is a safe procedure with excellent midterm results
      in high risk patients with ascending aortic aneurysm and aortic valve disease.

PMID- 19768300
TI  - Analysis of coronary vascular resistance and blood flow of venous graft in
      coronary artery bypass grafting.
AB  - OBJECTIVE: The aim of this study was to assess the coronary vascular resistance
      (CVR) and to analyze the flow differences through grafts in coronary artery
      bypass graft surgery. METHODS: Between 17 June and 15 July 2005, we assessed the
      coronary vascular resistance profile in 10 patients undergoing coronary artery
      bypass graft surgery by grafting a section of saphenous vein and checking CVR
      direct (preoperative) and indirect arterial pressure and blood flow during blood
      cardioplegic infusion. RESULTS: Significant differences between segments of
      coronary grafts with flow changes ranging from 36.52 to 100 ml/min were verified.
      CONCLUSION: Despite various factors that contribute to success or unsuccess of
      coronary grafts, the CVR preoperative assessment can be a possible method to
      estimate blood flow through the coronary graft implant during surgical procedure.

PMID- 19768301
TI  - Basic notions of heart rate variability and its clinical applicability.
AB  - Autonomic nervous system (ANS) plays an important role in the regulation of the
      physiological processes of the human organism during normal and pathological
      conditions. Among the techniques used in its evaluation, the heart rate
      variability (HRV) has arising as a simple and non-invasive measure of the
      autonomic impulses, representing one of the most promising quantitative markers
      of the autonomic balance. The HRV describes the oscillations in the interval
      between consecutive heart beats (RR interval), as well as the oscillations
      between consecutive instantaneous heart rates. It is a measure that can be used
      to assess the ANS modulation under physiological conditions, such as wakefulness
      and sleep conditions, different body positions, physical training and also
      pathological conditions. Changes in the HRV patterns provide a sensible and
      advanced indicator of health involvements. Higher HRV is a signal of good
      adaptation and characterizes a health person with efficient autonomic mechanisms,
      while lower HRV is frequently an indicator of abnormal and insufficient
      adaptation of the autonomic nervous system, provoking poor patient's
      physiological function. Because of its importance as a marker that reflects the
      ANS activity on the sinus node and as a clinical instrument to assess and
      identify health involvements, this study reviews conceptual aspects of the HRV,
      measurement devices, filtering methods, indexes used in the HRV analyses,
      limitations in the use and clinical applications of the HRV.

PMID- 19768302
TI  - Bicuspid aortic valve: theoretical and clinical aspects of concomitant ascending
      aorta replacement.
AB  - Bicuspid aortic valve (BAV) is associated with annuloaortic ectasia, dissection
      and ascending aortic aneurysm. The high incidence of this congenital malformation
      and aortic disease suggests a close correlation between the two phenomena.
      Abnormalities in different phases of cell migration of the neural crest might be
      responsible for the occurrence of abnormalities in the aortic valve, media layer
      of the ascending aorta and vessels of the aortic arch. Previous studies have
      shown that patients with normal BAV or slight dysfunction may present with
      dilation of the aortic root. The hemodynamic changes caused by BAV without
      stenosis or insufficiency seem to be an insufficient explanation for these
      findings. Several mechanisms have been proposed to explain the molecular and
      hystological aspects of this disease. We found a reduced fibrillin-1 content in
      both ascending aorta and pulmonary trunk as a possible cause. Histologically, the
      ascending aorta can present cystic medial necrosis and elastic fragmentation,
      similar to Marfan's disease. Some authors concluded that many patients, mainly
      those with aortic regurgitation, should have the aortic valve and the ascending
      aorta replaced at the same procedure, even if a mild dilatation (45 mm) is
      present in patients with BAV if life expectancy is anticipated to be greater than
      10 years to prevent further aneurysms or ruptures.

PMID- 19768303
TI  - Adaptation of bioassay to detect endothelium-derived relaxing factors from the
      canine atrial endocardium.
AB  - OBJECTIVE: The aim of this study was to assess the release of endothelium-derived
      relaxing factors from the endocardium of canine atrial appendage. METHODS: To
      study the release of endothelium-derived relaxing factor (EDRF) from intact
      atrial endocardial endothelium, tube-shaped sutures of canine atrial appendages
      were performed and effluents from these tubes were bioassayed (isolated perfused
      organ chamber system) for detection of EDRF in canine coronary artery. RESULTS:
      Effluent from the right atrial appendage caused a relaxation of 58.4 +/- 10.1%
      and the left atrial appendage 74.9 +/- 8.5% from the initial prostagladin F2alpha
      contraction in coronary artery. No significant statistical difference was
      detected in effluent from the right and left atrial appendages. This relaxation
      was abolished by treating the heart tubes with Triton X-100 and reduced by
      treatment with LNMMA, a competitive inhibitor of nitric oxide and with
      indomethacin, an inhibitor of the cyclo-oxygenase pathway, also indicating the
      release of vasodilatory prostanoids from the endocardial endothelium. CONCLUSION:
      This study showed for the first time, in vitro luminal release of EDRF and
      prostacyclin from the canine heart atrium. The ability of the endocardial
      endothelium to produce these factors could play an important role in preventing
      thrombus formation in the cardiac chambers.

PMID- 19768304
TI  - Off-pump transapical balloon-expandable aortic valve endoprosthesis implantation.
AB  - OBJECTIVE: The aortic valve replacement is a routine procedure, and involves
      replacement of the native valve/prosthesis. In most of the patients who undergo
      such procedure the risk is acceptable, but in some cases, such risk can justify
      contraindication. The minimally invasive transcatheter aortic valve implantation
      without cardiopulmonary bypass (CPB) has been shown to be viable, with lower
      morbidity and mortality. The aim of this study was to develop a catheter-mounted
      aortic bioprosthesis for implantation without CPB. METHODS: After developing in
      animals, three patients with high EuroSCORE underwent implantation. Case 1:
      patients with bioprosthesis dysfunction; Case 2: severe aortic stenosis; Case 3:
      dysfunction of aortic bioprosthesis. After minithoracotomy and under
      echocardiographic and fluoroscopic control, a balloon catheter was placed on
      aortic position and inflated. After, a second balloon with valved endoprosthesis
      was positioned and released under high ventricular rate. Echocardiographic and
      angiographic controls were performed and the patients were referred to ICU.
      RESULTS: In the first case, implantation without CPB was possible with
      appropriate results. The patient evolved with improvement of ventricular
      function. After, this patient developed bronchopneumonia, tracheoesophageal
      fistula and died due to mediastinitis. Autopsy confirmed proper valve positioning
      and leaflets preservation. The second case showed the device migration after
      inflation of the balloon, with the need for urgent median sternotomy, CPB and
      conventional valve replacement. This patient evolved well and was discharged from
      the ICU on the 14th postoperative day without complications. This patient
      developed respiratory infection, septic shock and died on the 60th postoperative
      day. The patient from the third case underwent successful implantation.
      CONCLUSION: The off-pump transapical implantation of catheter-mounted
      bioprosthesis was shown to be a feasible procedure. Technical details and
      learning curve require further discussion.

PMID- 19768305
TI  - Right atrial lipoma resection and partial reconstruction using bovine
      pericardium.
AB  - The primary heart tumors have an incidence varying from 0.001% to 0.28% of all
      tumors, reported in necropsies series. Lipoma consists of a benign tumour
      corresponding to about 8% of all primary heart tumors. When present, the symptoms
      are related to the size and location of such tumor. We report a case of a 27-year
      old man with a lipoma in the right atrium who underwent surgical treatment with
      tumor resection and partial reconstruction of the right atrium using bovine
      pericardium.

PMID- 19768306
TI  - Surgical treatment of primary cardiac rhabdomyosarcoma.
AB  - The authors report a case of a 16-year-old man who presented progressive dyspnea.
      At that time the diagnosis of rheumatic fever with mitral valve involvement was
      performed. The bidimensional echocardiogram showed presence of mobile mass inside
      the left atrium. The tumor presented lobules, projecting into the left ventricle
      during the diastole and provoking turbulence. The patient underwent surgical
      resection with postoperative course needing re-operation for mitral valve
      replacement. Histopathology has proven that such tumor was a primary cardiac
      rhabdomyosarcoma and the early clinical diagnosis of rheumatic mitral valve
      disease was very difficult.

PMID- 19768307
TI  - Hemoptysis and hemothorax as presentation of thoracic aortic rupture.
AB  - Thoracic aortic dissection is a disease of great mortality in its initial phase,
      but in some cases it can assume chronic course. We report a case of a patient
      with Stanford type A1 aortic dissection, admitted with mental confusion, dyspnea
      and event of severe hemoptysis. Electrocardiogram showed unspecific change and
      chest X-ray revealed opacification of the left hemithorax. Transthoracic
      echocardiogram did not show aortic dissection, but showed image similar to
      hemithorax leading to the suspicion of aortic rupture. The patient developed
      cardiovascular collapse and evolved to death. This case describes two unusual
      presentations of aortic dissection: hemothorax and severe hemoptysis.

PMID- 19768308
TI  - Ebstein's disease: the level of right ventricular dysfunction and the surgical
      approach.

PMID- 19768309
TI  - Partial anomalous pulmonary venous connection with interventricular
      communication: the rare and possible difficulty on the anatomic definition of
      left atrial isomerism.

PMID- 19768310
TI  - Repair of the total anomalous pulmonary venous connection.

PMID- 19768311
TI  - A question of quality.
AB  - Brazilian scientific journals conquer space in one of the main databases in the
      world. Experts explained to FAPESP Agency that the increase is due to the quality
      of the national research, but it can not be confused with increase in production
      .

PMID- 19768313
TI  - [Introduction].

PMID- 19768314
TI  - [The Brazilian Society of Cardiovascular Surgery and the insertion of
      cardiovascular surgeons to endovascular specialists].

PMID- 19768315
TI  - [Guidelines for surgery of aortic diseases from the Brazilian Society of
      Cardiovascular Surgery: updated in 2009].

PMID- 19768316
TI  - [The cardiovascular surgeon as an interventionist].

PMID- 19768317
TI  - [Equipment and supplies for endovascular procedures of the aorta].

PMID- 19768318
TI  - [Endovascular treatment for aorta diseases: overview. ].

PMID- 19768319
TI  - [Endovascular treatment for thoracic aorta aneurysms: step by step. ].

PMID- 19768320
TI  - [Endovascular correction for abdominal aortic aneurysm. ].

PMID- 19768322
TI  - [Qualified scientific publication in Brazilian Nursing].

PMID- 19768323
TI  - [Activities and participation of children with cerebral palsy according to the
      International Classification of Functioning, Disability, and Health].
AB  - Cerebral palsy is among the most common motor disabilities in our midst that
      limits individuals from carrying out their normal daily routines. The adjacent
      alterations, characterization, and participation of the child in these activities
      is not appropriated explored in the literature. The objective of this survey was
      to describe the capacity and performance of the children with cerebral palsy
      treated at an institution in the city of Fortaleza as to their capacity to carry
      out tasks and participate in daily life activities as stated in the International
      Classification of Functioning, Disability, and Health. Thirty-two children were
      evaluated. The data collected was grouped by the software Statistical Package of
      Social of Science (SPSS). The ICF had proportioned an objective description from
      cerebral palsy disabilities. It was clear that the impact that the disease has on
      the life of the children.

PMID- 19768324
TI  - [The nursing course of Universidade Federal de Juiz de Fora: 1977-1979].
AB  - Historic-social research aiming at: characterize the nursing superior teaching in
      Juiz de Fora city and to discuss the reason and motivations which determined the
      creation of Nursing Course of the Universidade Federal de Juiz de Fora. Primary
      source: written documents and oral testimony. The results discussion was guided
      by Pierre Bourdieu. In the 1970's, Education Ministry Department of University
      Subjects undertook efforts to create nursing courses in federal universities. As
      the process of negotiation meant to incorporate Hermantina Beraldo Nursing
      College to Universidade Federal de Juiz de Fora failed, in 1978 a Department of
      Nursing was bind to UFJF Medical College and, in 1970, the Nursing Course of this
      same university started functioning.

PMID- 19768325
TI  - [Nursing students' conceptions about the user of drugs].
AB  - STUDY'S OBJECT: Conceptions of nursing students on the approach to the drugs
      user. OBJECTIVES: To describe the conceptions of nursing students about the user
      of drugs. METHOD: Descriptive-exploratory study carried out with 321 students
      from 15 private nursing schools in the state of Rio de Janeiro. The scale of
      attitudes and beliefs NEADA was used to obtain the data between June 2006 and
      August 2007. The results demonstrate that the difficulties in dealing with the
      client who is a drug user are real, but the personal limitations of professionals
      in work with this kind of client still permeate the assistance, influencing care.

PMID- 19768326
TI  - [Practice of family health teams: challenges for the promotion of health care].
AB  - This article shows the results of a study which analyzed healthcare actions
      carried out by Family Health Teams. It is a qualitative research carried out in
      Belo Horizonte and Contagem, state of Minas Gerais. The subjects were 28 members
      of the Family Health Team. Data were collected through interviews. The results
      show a tendency to work a concept of health promotion, associated to disease
      prevention activities. Permanent education is very elementary is at a very early
      stage in the health services. We conclude that the activities carried out with a
      focus on inter-sectoral work are limited, compromising the consolidation of the
      merely technical healthcare model, which is based on health promotion. It can be
      seen, based on analysis of the practice of the teams, that there is little
      incentive to the empowerment of the subjects.

PMID- 19768327
TI  - [The use of the Calgary Model for assessment of families of the aged in clinical
      practice].
AB  - This qualitative study has as objective to present the experience to assessment
      of the families of dependent aged under the systemic approach. The Calgary Model
      was used as theoretical framework and as methodological strategy the case study.
      The data had been collected with five families of dependent older person, from
      September of December of 2005, by means of the instrument elaborated previously.
      The application of this model allowed doing the familiar analysis raising the
      main aspects of its structure, development and functioning. We believe that the
      nurse must search endorsement in the scientific literature and adopts pertinent
      instruments to contribute for the development of its abilities to do the familiar
      approach.

PMID- 19768328
TI  - [Access to the emergency service by clients with hypertensive crisis in a
      hospital in Fortaleza, CE, Brazil].
AB  - A hypertensive crisis is a sudden and symptomatic elevation of blood pressure at
      risk of acute deterioration of target organs. Although the prevalence in the
      literature of the burden is 1%, the risk of complications and death associated
      with the problem of health in the emergency services have revealed the need for
      deeper issues related to access to the service of health. It is a quantitative
      and descriptive research, held in a public hospital Fortaleza city, between April
      and July of 2006, with 118 patients. The results show that people with
      hypertensive crisis has sought health services, especially the emergency, in
      order to get care. The study indicates access as a key element in meeting the
      needs of users who seek the services of health, and the waiting time, the
      resolution and the reception, important parameters on the quality of care.

PMID- 19768329
TI  - [Nursing interventions for the prevention of accidental extubation].
AB  - The objective was to analyze results of the incidence of accidental extubation
      associated with nursing care. METHOD: Retrospective observational study, the
      intervention ahead, measured before and after the deployment of a guide
      extubations accidental The population of 142 patients, 72 patients in the
      retrospective phase and 70 in phase ahead, totaling 3771 days of ventilation.
      Data collected from prontuarios. RESULTS: 52.78% used tracheal tube and 62% were
      between 71 and 90 years with an average of days of ventilation of 26.5 days,.
      There were six (3.27) extubations before and two (1.03) after the deployment of
      guia. CONCLUSION, there was a decrease in the incidence of accidental extubation
      in the period studied, but one can not attribute this difference to the guide
      because other studies are needed.

PMID- 19768330
TI  - [Labor care delivered by nurses in the East zone of the municipality of Sao
      Paulo, SP, Brazil].
AB  - The aim of this study was to analyze delivery care by nurses in six public
      hospitals of the East zone in the municipality of Sao Paulo. A descriptive
      exploratory study was carried out from October 2006 to June 2007, with nursing
      leaders and 38 nurses who answered the questionnaire, indicating frequency they
      performed delivery care related activities, as well as any possible obstacles or
      difficulties to exercise their functions. The results showed that nurses had no
      means to operationalize their work due to institutional and organization barriers
      that they had to deal with. It was concluded that to completely perform their
      work regarding delivery care, nurses must count with more favorable structures
      and to strengthen their professional identity, thus assuming greater
      qualification and power.

PMID- 19768331
TI  - [Interpreting the hospitalization experiences of patients with spine lesion].
AB  - Qualitative study with theoretical axis in symbolic interactionism interpretative
      of Norman Denzin that had as objective to comprehend the meanings of experiences
      lived by being victim of spine lesion in context hospital and to describe the
      narratives in range of experiences lived. The subjects of research were seven
      patient victims of spine lesion traumatic hospitalized in unity of neurology of
      Institute Dr. Jose Frota, sited in Fortaleza/Ce. Interpreted hard fronting to
      balance of oneself, given to sudden breaking of trajectory of their lives, the
      organic alterations acquired that pass to be motives of fears, uncertain, non
      comfort and menace to life that had along their families.

PMID- 19768332
TI  - [Breast self examination: meanings for patients in chemotherapeutic treatment].
AB  - To verify the practice and to identify the meaning of the breast self examination
      among women with cancer and were submitted to the chemotherapy were objectives of
      this work. It was a qualitative research, using the speech of the women who are
      breast cancer carriers in the Hospital das Clinicas of the Universidade Federal
      do Triangulo Mineiro, Uberaba, MG, Brazil through semi-structured interviews. The
      collected material was submitted to the analysis of the simplified content
      proposed by Thiollent. The interviewees owned knowledge on the existence and
      Importance of breast self examination, however, many did not practice it
      correctly or ignored the periodicity and technic indicated, there being, this
      way, need to develop effective interventions to promote the understanding of the
      feminine population concerning the importance in adopting practices aimed at the
      precocious diagnosis of the mammary cancer.

PMID- 19768333
TI  - [Social representations of women who breastfeed about breast feeding and the use
      of pacifiers].
AB  - The objective was to identify the different meanings that surround the
      breastfeeding and the use of pacifiers of a group of mothers of children under
      six months old. Adopted to the precepts of qualitative research methodology.
      Interviews were conducted semi-structured individual, transcribed in full and
      analyzed using the technique to analyse the content of Bardin. The comprehensive
      analysis of speeches revealed the presence of representations which can carry
      interference in the decision to breastfeed - both positive, as negatively. In
      that sense, it is important that health professionals, know the context in which
      these women are found, especially their doubts, fears, myths and beliefs in
      relation to breastfeeding, thus acting in favour of lactation.

PMID- 19768334
TI  - [Nomenclature of nursing interventions to the medical clinic of a teaching
      hospital].
AB  - Descriptive-exploratory study developed with the aim of building affirmative
      nursing interventions based on the Bank of Language Special Terms of Nursing, the
      Nomenclature of Nursing Diagnostics of the Medical Clinic and the ICNP, Seven
      Axis Model. The affirmative built were subjected to a validation process,
      considering as validated when reaching a > 0.80 concordance index, by nurses who
      work in the referred clinic, and who agreed to participate. It is waited that the
      use of this nomenclature, while technological instrument, allow the employment of
      the clinical reasoning, attendance individualization and, consequently,
      stimulates the nurses to question and to modify its professional performance in
      the assistance, the management, education and the research.

PMID- 19768335
TI  - [Prevention of breast cancer in elderly women: a review].
AB  - This is a national literature review that aimed to reflect on the prevention of
      breast cancer in the elderly woman. This curiosity arose from the observation of
      demographic transition and of course Brazilian feminisation of old age, which
      imposes specific demands assists and integrals for this population segment. It is
      emphasized the need to extend the knowledge about the problem, as well as
      overcoming the negligence in the prevention of this disease, especially in old
      age. Focused are two topics reflective: Aging Women, Health and Gender Gap and
      the completeness of assistance to the elderly woman: awareness to release. It is
      expected with this reflection subsidize quality improvement of the assistance,
      promote the inclusion of this issue in education and stimulate new research.

PMID- 19768336
TI  - [Nursing care for the aged with dementia and with behavioral symptoms].
AB  - In the course of dementia, behavioral disorders are highly prevalent and are
      frequently associated with the stress of caregivers. This study aims to identify
      in scientific literature the types of dementia associated with behavioral and
      psychological symptoms (BPSD); describe the non-pharmacological management of
      these alterations, and describe the nursing interventions in this context. The
      literature in the field of geriatrics and nursing was searched. It became evident
      that the nursing care provided to the demented elderly goes farther beyond the
      basic care and depends on the active participation of the family. The
      identification of strategies to minimize and manage the behavioral symptoms is an
      important contribution that nursing can give to geriatrics.

PMID- 19768337
TI  - [Analysis of national publications about distance education in nursing].
AB  - The objective is to examine the publications working in the Distance Education in
      nursing in the databases from 2005 to 2009. Study of literature review conducted
      in the databases of the Virtual Health Library (Lilacs, Scielo and Bdenf) in the
      period from 19/02/09 to 24/04/09 in 20 selected references were reviewed. It is
      tonic in the discussions: the development of training courses for nurses and
      midwives as well as courses in graduate programs via Distance Education. There is
      an evolution of Distance Education in nursing with possibilities of teaching in
      virtual environment for learning is everlasting and take into account some
      constraints relevant to interactivity as the availability of training courses and
      disciplines in undergraduate courses.

PMID- 19768338
TI  - [Methodology for the use of chat in nursing].
AB  - The purpose of this study was to describe the methodology of the use of chat for
      real-time communication in a group of nursing research. The role of coordinator
      understands the dimensions of planning, mediation and technology. Each dimension
      can determine the success or failure of communication. They should be seen in an
      integrated and modified some of them interfere with the quality of the final
      outcome of the activity. The software of communication was adopted by Skype allow
      free communication among many users in real time. To implement the chat were down
      five steps: opening, host / heating, the staff development, synthesis and
      closure. The methodology allowed optimization and flexibility of time,
      organization of activities and range of goals.

PMID- 19768339
TI  - [Moral distress and the ethical dimension in nursing work].
AB  - Nurses face moral problems, moral dilemmas and moral distress in their
      professional daily. The moral distress manifests itself when nurses demonstrate
      difficulties to face situations morally appropriate following their conscious.
      The study aims to focus about the nurses' moral distress and their relationship
      with moral problems and moral dilemmas presenting concepts, moral distress
      experiences and possible strategies to be adopted to face it. To focus on the
      moral distress provoked by facing the moral problems and dilemmas in nursery work
      seems to be primordial not just to reveal a phenomenon still a little known even
      experienced almost every day but, also to headline the need of problematization
      and valorization of the ethical dimension of work in health.

PMID- 19768340
TI  - [Rooming-in as a space for maternal and professional care].
AB  - This is a theoretical reflection about maternal care in the context of Rooming
      in. It is based on Winnicott's concepts of Primary Maternal Preoccupation,
      Maternal Care, and Good Enough Environment. Rooming-in is conceived as an
      adequate place for establishing a relationship between mother and child which is
      favorable to maternal care. While in Rooming-in, the mother lives a peculiar
      mental status, the primary maternal preoccupation, which goes stronger along
      pregnancy and is maximal during childbirth. Perceiving Brazilian maternity
      hospital as a place for care, we see nursing care as an important aid in the
      interaction between mother and baby, supporting women along this peculiar state
      of mind.

PMID- 19768341
TI  - [Planning human resources in nursing: challenge for the leadership].
AB  - This study proposes an essay of issues involving human resources planning in
      nursing in the hospital sector in our current reality, discussing possible topics
      for future research. This is a retrospective of the evolution of research on
      determining the number of staff in Brazil, and the incorporation of new
      instruments to evaluate the work load based on the degree of dependency of the
      patients and actions in care. The impact of the quantity and quality of human
      resources on the results of care is discussed, and the role of leaders in
      adapting the staff composition, in order to supply safe, risk-free care to the
      patients and their families, seeking a management model for health practices from
      the perspective of complex care.

PMID- 19768342
TI  - [Applications of Orem's Theory in addressing interventions during pregnancy and
      climateric].
AB  - The aim of this paper is to develop applications of Orem's Theory of Self Care in
      order to address nursing interventions during pregnancy and menopause, and to
      determine its usefulness as a theoretical framework for addressing self care
      during stages of development. It is concluded that the application by nurses and
      midwives of this theoretical framework, in assisting women during pregnancy and
      menopause, contributes to identifying the requirements of self care, the required
      interventions, necessity of self care and the methods of assistance that women
      require with special emphasis on training and development of self care
      procedures.

PMID- 19768343
TI  - [The Project on a Large Scale in its first times: time for a recall].
AB  - In this work we rebuilt the first attempts on the creation of the Program of
      Formation on a Large Scale of Elementary and High School people for basic health
      services. We examined the Program of Formation on a Large Scale from its
      beginning, being supported by documentary sources, such as Izabel dos Santos's
      interview, which filled in all the meanings of this experience. In the
      investigations, we went trough the purpose and the procedures of the proposal on
      a national scale. According to our point of view, this experience acquired a
      wider meaning of qualification: in which the focal point of the work, as a
      condition to workers' formation process, constituted as a methodological
      pedagogical purpose of qualification at the work environment in order to obtain a
      critical professional.

PMID- 19768344
TI  - [Caring for the self, for another, and for 'us' within a complexity perspective].
AB  - This study is an experience report of a reflective practice developed with
      nursing professionals in a public hospital in Santa Catarina, Brazil about the
      problem of relationships in caring for one's self, another, and for 'us', in
      different dimensions, within the perspective of the Complexity paradigm. Five
      workshops were organized and carried out, encompassing three meetings each, with
      previously chosen themes. From the systematic analysis of the participants'
      speech content, some units of meaning emerged. This practice brought
      comprehension concerning established iterations and associations in the I-other
      us relationship closer together, as human beings, in the I-other-us-environment
      relationship, and in the relationship each human being has with him/herself,
      based on the mobilization/undulations/private and reciprocal exchanges of living
      and living with others in a complex world/scenario.

PMID- 19768345
TI  - [Development and implementation of Animals-Assisted Therapy in a university
      hospital].
AB  - This report refers to the experience of the Board of Nursing of Hospital Sao
      Paulo, Universidade de Sao Paulo, in the development and implantation of Animal
      Assisted Therapy, as one of its projects humanization of hospital: 'Projeto
      Amicao'. Aiming to offer patients a positive experience that differs from the
      routine of the hospital environment, some units of the Hospiral Sao Paulo
      received the visit of an animal for sessions of Animal-Assisted Therapy. The
      results achieved among patients and its companions and health professionals were
      positive, in addition to arouse the attention and the interest of other health
      institutions and the media. It is thus evidenced the importance of reporting the
      experience of 'Projeto Amicao' in the hospital.

PMID- 19768346
TI  - [The visibility of nurse as a profession: recognizing conquests and gaps].
AB  - This experience report aimed at discussing and reflecting about undergraduate
      classes, literature and discussions conducted in seminaries with nursing
      students, the conquests and the gaps that are reflected in the visibility of the
      nursing profession. The 'Job market in Nursing and new modalities of rendering
      services'. The students see the Nurse as a professional focused on care. The
      categories that emerged from the data referring to the nursing students' view
      just before graduating are: advances and conquests, professional satisfaction and
      gaps in the profession. It is important to develop the political competence with
      a broadened view of the nursing profession as a social compromise of citizenship
      in the conquest of living more healthy.

PMID- 19768347
TI  - Simultaneous penile and signet ring cell bladder carcinoma in renal transplant
      recipient: a first case.
AB  - The incidence and prevalence of cancer increase with time after transplantation.
      Therefore, a risk-adapted screening process is very important in order to
      identify low-grade malignancies early in their development. This provides the
      opportunity to initiate appropriate immunosuppressive regimens depending on the
      tumor type and stage of development. The first case presented is one of a 65-year
      old patient with a double genitourinary carcinoma (penis and bladder). The
      patient received kidney transplantation 7 years prior to this event. After
      adequate surgical treatment (partial amputation of the penis for squamous cell
      carcinoma and complete transurethral resection of bladder adenocarcinoma), the
      patient was noted to be free of tumor recurrence and had functioning renal graft
      with a 2-year follow-up.

PMID- 19768348
TI  - Self-efficacy and the sense of coherence: narrative review and a conceptual
      synthesis.
AB  - In this study, the authors develop an exploratory synthesis of two major health
      concepts: Antonovsky's sense of coherence and Bandura's beliefs in one's own
      efficacy. Reinterpretation of each study in the light of the other can lead to
      greater conceptual development and expand existing knowledge. The mutual themes
      are presented with an explanation of their contribution to broader conceptual
      discussions. The existence of some similarities between the two concepts is
      suggested. Researchers can obtain valuable and additional arguments through cross
      fertilization of ideas across presented studies united by shared assumptions.
      Further research is recommended among various age groups and social backgrounds
      in order to verify the possible benefits of such theoretical development.
      Theoretical and practical implications of such a synthesis are presented.

PMID- 19768349
TI  - A special, strict, fat-reduced, and carbohydrate-modified diet leads to marked
      weight reduction even in overweight adolescents with Prader-Willi syndrome (PWS).
AB  - Hyperphagia is a frequent symptom in patients with Prader-Willi Syndrome (PWS)
      and results in marked obesity with the risk of metabolic and cardiovascular
      complications. Previously, we reported that our special diet for PWS patients is
      effective in the long run, if started early at about 2 years of age. Our
      objective in this study was to investigate if our special diet is also effective
      in PWS adolescents who are already overweight. We provided a strict, fat-reduced,
      and carbohydrate-modified diet, consisting of 10 kcal/cm height, to five
      adolescents (two female, three male) with PWS. Patients were prospectively
      followed at our center for 2-6 years. BMI, BMI-SDS, and Weight-for-Height Index
      were recorded over that period. The special diet was started at a mean age of 16
      years (range: 14.1-18.9 years) and initial BMI was 41.3 kg/m(2) (range: 32.4-55.5
      kg/m(2)), corresponding to BMI-SDS +3.6 (range: +2.8 to +4.5 SDS). Weight-for
      Height Index was 243% (range: 190-339%). After 2 years of the diet, BMI decreased
      to 33 kg/m(2) (range: 26.7-38 kg/m(2)), as well as BMI-SDS +2.7 (range: 1.7-3.4
      SDS) and Weight-for-Height Index to 191% (range: 157-232%); p < 0.01. The special
      diet was still effective in reducing weight after 4-6 years, with a mean BMI of
      30.5 kg/m(2) (range: 24.6-34.5 kg/m(2)) and a mean BMI-SDS of +2.1 (range: 0.7
      2.9). We conclude that in a period of 2-6 years, our strict, fat-reduced, and
      carbohydrate-modified diet, with 10 kcal/cm height, is effective even in
      adolescents with PWS who are already overweight.

PMID- 19768350
TI  - Castleman's disease: an intrapulmonary form with intrafissural development.
AB  - Castleman's disease (CD) is an uncommon, mainly benign, lymphoproliferative
      disorder of unknown etiology, mostly involving the mediastinum. Parenchymal lung
      involvement of the disease is exceedingly rare. We describe a case of CD in a 23
      year-old woman with a 4-year history of recurring dyspnea and nonproductive
      cough, whose chest X-ray showed an abnormal shadow of the right hilum. Chest
      computed tomography confirmed the presence of a tissue-density mass of the right
      lower lobe, demonstrating poor contrast enhancement, associated with multiple
      laterotracheal and mediastinal lymphadenopathies. The patient underwent curative
      surgery, revealing a right hilar compressive mass, with an intrafissural
      development between the superior and middle lobes. Pneumonectomy was performed
      due to profuse bleeding. This case of CD is particular because of its unusual
      intrapulmonary location and its intrafissural development. Poor contrast
      enhancement is atypical in CD.

PMID- 19768351
TI  - Coronary artery circumferential stress: departure from Laplace expectations with
      aging.
AB  - Normal, youthful arteries generally maintain constant radius/wall thickness
      ratios, with the relationship being described by the Laplace Law. Whether this
      relationship is maintained during aging is unclear. This study first examines the
      Laplace relationships in postmortem coronary arteries using a novel method to
      correct measurements for postmortem artifacts, uses data from the literature to
      provide preliminary validation, and then describes histology associated with low
      circumferential stress. Measurements of radius and wall thickness, taken at sites
      free from atheromas, were used with national population estimates of age-, gender
      , and race-specific blood pressure data to calculate average circumferential
      stress within demographic groups. The estimated circumferential stress at ages 55
      74 years was about half that at ages 18-24 years because of a disproportionate
      increase of wall thickness relative to artery radius at older ages, violating the
      expected relationships described by the Laplace Law. Arteries with low
      circumferential stress (estimated at sites distant from atherosclerosis) had more
      necrotic atheromas than arteries with high stress. At sites with low stress and
      intimal thickening, smooth muscle cells (SMCs) were spread apart, thereby
      diminishing their density within both the intima and media. Thus, older arteries
      displayed both low circumferential stress and abundant matrix of low cellularity
      microscopically. Such changes might alter SMC-matrix interactions.

PMID- 19768352
TI  - Cerebrospinal fluid biomarkers and prediction of conversion in patients with mild
      cognitive impairment: 4-year follow-up in a routine clinical setting.
AB  - Mild cognitive impairment (MCI) is a very common syndrome in elderly people, with
      a high risk of conversion to dementia. Several investigations have shown the
      usefulness of cerebrospinal fluid (CSF) biomarkers (Abeta42, total tau [T-tau],
      and phosphorylated tau [P-tau]) in predicting the progression to Alzheimer's
      disease (AD). We report a 4-year follow-up of MCI patients who underwent CSF
      evaluation for biomarker assessment, in order to further evaluate the usefulness
      of CSF analysis in predicting the conversion to dementia in a routine clinical
      setting. We identified 55 patients with MCI among the consecutive patients,
      referred from 2001 to 2003 to our Memory Clinic for cognitive disorders, who
      underwent a complete diagnostic assessment, including lumbar puncture (n = 273).
      At the end of the follow-up, 31 MCI patients (56%) did not progress to dementia
      (stable MCI), while 24 (44%) developed a dementia condition. At baseline, the
      mean levels of CSF Abeta42, T-tau, and P-tau were significantly altered in MCI
      patients who were converting to dementia with respect to those with stable MCI.
      All MCI patients with the three altered CSF biomarkers developed dementia within
      1 year. Among the stable MCI patients, none showed all three pathological values
      and only one subject had the pathological value of P-tau. Early diagnosis of
      dementia and, specifically, a correct prediction of MCI outcome represent a
      primary goal. To this respect, the role of CSF biomarkers seems to be crucial in
      a routine clinical setting.

PMID- 19768353
TI  - Enhancing the delivery of erythropoietin and its variants into the ischemic
      brain.
AB  - The hematopoietic growth factor erythropoietin (EPO) and its neuroprotective, but
      not hematopoietic, variants asialoEPO, carbamylated EPO (CEPO), and low sialic
      acid EPO (Neuro-EPO) are attractive candidates for stroke treatment. Due to their
      large molecular weight, these proteins enter the brain only to a minor extent
      when intravenously administered, which has raised the question for alternative
      delivery strategies, among which intranasal delivery may certainly be an
      attractive choice, as the review by Garcia Rodriguez and Sosa Teste in this
      journal points out. Before this strategy may be considered clinically applicable,
      however, more and, in particular, quantitative information is needed about (a)
      the temporospatial accumulation of EPO and its variants in the brain tissue both
      in animals and nonhuman primates, and (b) the accumulation of EPO and its
      variants in the human cerebrospinal fluid.

PMID- 19768354
TI  - The nasal route as a potential pathway for delivery of erythropoietin in the
      treatment of acute ischemic stroke in humans.
AB  - Intranasal delivery provides a practical, noninvasive method of bypassing the
      blood-brain barrier (BBB) in order to deliver therapeutic agents to the brain.
      This method allows drugs that do not cross the BBB to be delivered to the central
      nervous system in a few minutes. With this technology, it will be possible to
      eliminate systemic administration and its potential side effects. Using the
      intranasal delivery system, researchers have demonstrated neuroprotective effects
      in different animal models of stroke using erythropoietin (EPO) as a
      neuroprotector or other different types of EPO without erythropoiesis-stimulating
      activity. These new molecules retain their ability to protect neural tissue
      against injury and they include Asialoerythropoietin (asialoEPO) carbamylated EPO
      (CEPO), and rHu-EPO with low sialic acid content (Neuro-EPO). Contrary to the
      other EPO variants, Neuro-EPO is not chemically modified, making it biologically
      similar to endogenous EPO, with the advantage of less adverse reactions when this
      molecule is applied chronically. This constitutes a potential benefit of Neuro
      EPO over other variants of EPO for the chronic treatment of neurodegenerative
      illnesses. Nasal administration of EPO is a potential, novel, neurotherapeutic
      approach. However, it will be necessary to initiate clinical trials in stroke
      patients using intranasal delivery in order to obtain the clinical evidence of
      its neuroprotectant capacity in the treatment of patients with acute stroke and
      other neurodegenerative disorders. This new therapeutic approach could
      revolutionize the treatment of neurodegenerative disorders in the 21st century.

PMID- 19768355
TI  - Predictors of emotional problems and physical aggression among children of Hong
      Kong Chinese, Mainland Chinese and Filipino immigrants to Canada.
AB  - BACKGROUND AND STUDY AIMS: Data from the New Canadian Children and Youth Study
      (NCCYS), a national study of immigrant children and youth in Canada, are used to
      examine the mental health salience of putatively universal determinants, as well
      as of immigration-specific factors. Universal factors (UF) include age, gender,
      family and neighbourhood characteristics. Migration-specific (MS) factors include
      ethnic background, acculturative stress, prejudice, and the impact of region of
      resettlement within Canada. METHODS: In a sample of children from Hong Kong, the
      Philippines and Mainland China, the study examined the determinants of emotional
      problems (EP), and physical aggression (PA). A two-step regression analysis
      entered UF on step 1, and MS variables on step 2. RESULTS: Universal factors
      accounted for 12.1% of EP variance. Addition of MS variables increased explained
      variance to 15.6%. Significant UF predictors: parental depression, family
      dysfunction, and parent's education. Significant MS variables: country of origin,
      region of resettlement, resettlement stress, prejudice, and limited linguistic
      fluency. UF accounted for 6.3% of variance in PA scores. Adding migration
      specific variables increased variance explained to 9.1%. UF: age, gender,
      parent's depression, family dysfunction. MS: country of origin, region of
      resettlement, resettlement stress, and parent's perception of prejudice.
      CONCLUSIONS: Net of the effect of factors affecting the mental health of most, if
      not all children, migration-specific variables contribute to understanding
      immigrant children's mental health.

PMID- 19768356
TI  - Vertical fluxes and accumulation of trace metals in superficial sediments of the
      Rio de la Plata estuary, Argentina.
AB  - Superficial sediments and settling material collected in Buenos Aires coastal
      area were analyzed to evaluate the accumulation and sources of trace metals.
      Residual elements showed homogeneous sedimentary concentrations (Fe: 23,846 +/-
      4,367; Ni: 10 +/- 2.7; Mn: 706 +/- 314 MUg g(-1)) whereas anthropogenic metals
      presented exponentially decreasing offshore gradients (Zn: 98 +/- 69; Cr: 28 +/-
      21; Cu: 19 +/- 15; Pb: 18 +/- 13 MUg g(-1)). Anthropogenic impact was evaluated
      through metal-Fe relationships, Fe-normalized enrichment factors and sediment
      quality guidelines. The slopes of metal-Fe regressions from background sites were
      comparable to upper crust metal ratios, excepted Cr which is impoverished, and Mn
      which is diagenetically enriched. Metal-Fe relationships also hold for most 2.5
      km offshore sites but with higher slopes denoting human influence, and are
      completely lost in 1-2.5 km sediments and trap material which plot over the
      regressions and exceed sediment quality guidelines.

PMID- 19768357
TI  - 210Pb in forage consumed by dairy cows.
AB  - The aim of this research was to determine (210)Pb concentrations in forage from
      farms located in the municipalities of Pedra and Venturosa, in the Brazilian
      state of Pernambuco, where rolled blocks of mafic rock with a high percentage of
      U(3)O(8) were found. The concentrations of (210)Pb varied from 2 to 503 Bq kg(-1)
      in the forage dry matter samples evaluated. Due to the elevated levels of (210)Pb
      in the forage samples, it is concluded that this radionuclide is highly available
      to be ingested by dairy cows and this could represent a hazard to the human
      population due to possible milk contamination.

PMID- 19768358
TI  - Metal accumulation and antioxidant enzyme activity in C. gariepinus, catfish, and
      O. mossambicus, tilapia, collected from Lower Mguza and Wright Dams, Zimbabwe.
AB  - The aim of this study was to measure antioxidant enzyme activities as biological
      indicators of pollution in tissues of two species of fish. Five Clarius
      gariepinus and three Oreochromis mossambicus were collected from Umguza Dam
      (polluted dam) whilst seven C. gariepinus and eight O. mossambicus were collected
      from Wright Dam (relatively pristine dam). Diphosphotriphoshodiaphorase and
      catalase activities were consistently lower (42 +/- 2% and 78 +/- 20%,
      respectively) in liver whilst malondialdehyde levels were two times higher in
      muscles of both species of fish collected from Umguza Dam. However,
      seleniumdependent glutathione peroxidase (Se-GPX) activity was elevated four-fold
      in liver and gills of O. mossambicus collected from Umguza Dam. Metal levels were
      two to five times higher in muscles of both species of fish collected from Umguza
      Dam. Fish from Umguza Dam seem to have responded to pollution by increasing Se
      GPX specificactivity in an effort to detoxify peroxides produced as a result of
      metal induced oxidative stress.

PMID- 19768359
TI  - Effect of cadmium accumulation on anti-inflammatory activity in two Eucomis
      species.
AB  - Eucomis species (Hyacinthaceae) are widely used in South Africa as traditional
      medicine. The bulbs are used to alleviate a variety of symptoms including pain
      and inflammation. High levels of cyclooxygenase-1 and -2 (COX-1 and COX-2)
      inhibitory activity have been associated with certain Eucomis species. The aim of
      this study was to quantify cadmium(Cd) accumulation and examine its effect on COX
      1 and COX-2 anti-inflammatory activity in Eucomis autumnalis and Eucomis humilis.
      Cadmium application at 2 mg L(-1) over a 6 week period revealed a substantial
      difference in total Cd accumulation in E. autumnalis and E. humilis (40.2 and
      15.3 mg Cd kg-1, respectively). When supplied with Cd at 2 mg L(-1), E. humilis
      bulbous extracts showed lower inhibitory activity than the control for both COX-1
      and COX-2. E. autumnalis bulbous extracts had greater COX-1 activity compared to
      the control. While COX-2 activity was suppressed. Researchers should be aware of
      the effect of environmental contaminants when reporting on biological activity of
      crude plant extracts.

PMID- 19768360
TI  - High concentrations of polycyclic aromatic hydrocarbons found in water and
      sediments of car wash and Kisat areas of Winam Gulf, Lake Victoria-Kenya.
AB  - Mean concentrations of selected USEPA priority polycyclic aromatic hydrocarbons
      (PAHs) in surface sediments and water samples from Car Wash and Kisat areas of
      Winam Gulf, Lake Victoria in Kenya have been determined using GC-FID and GC-MS.
      Sampling was done during the rainy season in April 2006. The PAH concentrations
      in sediment and water ranged from 0.04 to 31.95 microg/g dry weight and 3.32 to
      55.8 microg/L, respectively, depending upon the sampling location. The total
      concentration levels of PAHs in both the sediment and water phase in this study
      were found to be much higher compared with those reported from other regions
      worldwide, revealing significant PAH pollution of Car Wash and Kisat areas of
      Kisumu city bay as a consequent of anthropogenic activities as described in the
      text. The GC-detected PAHs were confirmed by GC-MS.

PMID- 19768361
TI  - Estimated PBDE and PBB Congeners in soil from an electronics waste disposal site.
AB  - This study estimated PBDE and PBB congener emissions into the environment from
      three different e-waste disposal sites that consisted of rude broilers (RB), acid
      baths (AB) and end-up dumps (ED). Different PBDE and PBB congener profiles were
      analyzed, and some of their emission sources were discussed. For the examined
      sites, the levels of SigmaPBB and SigmaPBDE were highest at ED (SigmaPBB 1943.86
      ng/g, dw; SigmaPBDE 990.87 ng/g, dw), followed by RB (SigmaPBB 704.58 ng/g, dw;
      SigmaPBDE 799.27 ng/g, dw) and finally AB (SigmaPBB 108.78 ng/g, dw; SigmaPBDE
      171.18 ng/g, dw). PBE-209 (AB 48.67 ng/g, 28.43%; RB 160.23 ng/g, 20.05%; ED
      234.12 ng/g, 23.63%) and PBE-203 (AB 51.23 ng/g, 29.93%; RB 130.34 ng/g, 16.31%;
      ED 93.41 ng/g, 9.43%) exhibited the highest concentrations when compared to the
      other congeners. Furthermore, high levels of deca-BDE (BDE-209) were observed in
      AB (48.67 ng/g, 28.43%) and RB sites (160.23 ng/g, 20.05%), which was in
      accordance with the large amount of these materials in electronics products in
      China.

PMID- 19768362
TI  - Mercury, lead and copper in feathers and excreta of small passerine species in
      relation to foraging guilds and age of feathers.
AB  - In the present study excreta and feathers of five species of adult passerine
      birds from Montepulciano wetland (Siena, Italy) were assayed for trace elements
      between January and August 2006. Lead concentrations varied from 16.31 to 26.50
      mg/kg and were found strictly related to the age of feathers. Copper levels were
      found to be high mainly in insectivorous birds (9.68 mg/kg) and were probably
      influenced by local use of copper-based agricultural fungicides. Mercury
      accumulation in feathers varied between species from 0.08 to 0.73 mg/kg. The role
      offeeding habits on trace elements levels in feathers and excreta is discussed.

PMID- 19768363
TI  - Appraisal of the Imaizumi modification of the Beger procedure: the TWMU
      experience.
AB  - BACKGROUND/PURPOSE: We developed the Imaizumi modification of the Beger
      procedure, a duodenum-preserving pancreatic head resection. The Imaizumi
      modification allows for removal of more of the subtotal pancreatic head than in
      the conventional Beger procedure, including the intrapancreatic bile duct, for
      chronic pancreatitis with common bile duct stenosis. A retrospective study was
      performed to evaluate the efficacy of the Imaizumi modification compared to a
      pylorus-preserving pancreaticoduodenectomy (PPPD), based on the early and late
      postoperative results. METHODS: A group of 14 patients who underwent the Beger
      procedure with the Imaizumi modification to treat chronic pancreatitis from
      November 1997 to December 2005 was investigated retrospectively. This group was
      compared to a group of 21 patients who underwent PPPD from November 1997 to
      December 2003. The median follow-up period was 3.6 years (range 3.1-5.7 years)
      for the Imaizumi modification group and 4.0 years (range 3.0-8.3 years) for the
      PPPD group. RESULTS: A pancreatic fistula formed in 7% of the Imaizumi
      modification patients (PPPD 5%), pain relief was achieved in 92% (PPPD 94%),
      complete professional rehabilitation was achieved in 71% (PPPD 67%), insulin
      dependent diabetes mellitus was present in 43 versus 36% before the procedure
      (PPPD 62 versus 38% before the procedure), and body weight improved in 79% (PPPD
      48%). No significant differences were found between the two groups for the early
      postoperative complications and the late postoperative outcome 3 years after the
      procedure. However, the Imaizumi modification group exhibited an encouraging
      tendency to have a lower rate of new-onset exocrine and endocrine insufficiency
      than the PPPD group. CONCLUSIONS: Our Imaizumi modification of the Beger
      procedure, including intrapancreatic bile duct resection, represents a useful
      alternative for the treatment of chronic pancreatitis with an inflammatory mass
      and bile duct stenosis in the pancreatic head.

PMID- 19768365
TI  - Insertion of large amino acid repeats and point mutations contribute to a high
      degree of sequence diversity in the X4 protein of tomato ringspot virus (genus
      Nepovirus).

PMID- 19768364
TI  - Characterization of two genes involved in chromate resistance in a Cr(VI)-hyper
      resistant bacterium.
AB  - Mechanisms underlying chromate resistance in Cr(VI)-hyper-resistant Pseudomonas
      corrugata strain 28, isolated from a highly Cr(VI) polluted soil, were studied by
      analyzing its two Cr(VI)-sensitive mutants obtained by insertion mutagenesis. The
      mutants, namely Crg3 and Crg96, were characterized by the identification of
      disrupted genes, and by the high-throughput approach called Phenotype MicroArray
      (PM), which permitted the assay of 1,536 phenotypes simultaneously. Crg3 and
      Crg96 mutants were affected in a malic enzyme family gene and in a gene encoding
      for a RecG helicase, respectively. The application of PM provided a wealth of new
      information relating to the disrupted genes and permitted to establish that
      chromate resistance in P. corrugata strain 28 also depends on supply on NADPH
      required in repairing damage induced by chromate and on DNA integrity
      maintenance.

PMID- 19768367
TI  - Neuromyotonia in idiopathic hypoparathyroidism.
AB  - Alpha 62-year-old man was presented with bilateral cataract, proximal muscle
      weakness and difficulty in relaxing the hands after voluntary contraction.
      Idiopathic hypoparathyroidism was diagnosed. Electrophysiological study showed
      spontaneous motor unit action potentials, occurring and disappearing abruptly, as
      duplets, triplets and multiplets, with an intra-burst frequency of up to 100 Hz
      and some of them waning in amplitude, findings consistent with neuromyotonia.

PMID- 19768366
TI  - Effects of treadmill training on walking economy in Parkinson's disease: a pilot
      study.
AB  - Gait disturbances are frequent in Parkinson's disease (PD) and are associated
      with increased energy expenditure during walking. This study evaluated whether
      the effects of treadmill training are associated with an improvement of walking
      economy. Ten patients with idiopathic PD underwent treadmill training (30 min,
      three times a week for 4 weeks). Walking performance (Tauimed Up and Go, 6-min
      and 10-m walking tests) and metabolic function (oxygen uptake, heart and
      respiratory rate) were evaluated before training, at the end of treatment and
      after 30 days with two different graded exercises (treadmill and cycloergometer).
      Training significantly improved walking performance. Oxygen uptake, and heart and
      respiratory rates were significantly decreased only during graded exercise on the
      treadmill, but not on the cycloergometer. Treadmill training reduces energy
      expenditure during walking in PD, but the improvements of metabolic walking
      economy are associated with the specifically trained motor activity.

PMID- 19768368
TI  - Lack of effect of cannabis-based treatment on clinical and laboratory measures in
      multiple sclerosis.
AB  - The endocannabinoid system (ECS) is involved in the pathophysiology of multiple
      sclerosis (MS), and relief from pain and spasticity has been reported in MS
      patients self-medicating with marijuana. A cannabis-based medication containing
      Delta(9)-tetrahydrocannabinol and cannabidiol (Sativex) has been approved in some
      countries for the treatment of MS-associated pain. The effects of this
      pharmaceutical preparation on other clinically relevant aspects of MS
      pathophysiology, however, are still unclear. In 20 MS patients, we measured the
      effects of Sativex on clinically measured spasticity and on neurophysiological
      and laboratory parameters that correlate with spasticity severity or with the
      modulation of the ECS. Sativex failed to affect spasticity and stretch reflex
      excitability. This compound also failed to affect the synthesis and the
      degradation of the endocannabinoid anandamide, as well as the expression of both
      CB1 and CB2 cannabinoid receptors in various subpopulations of peripheral
      lymphocytes.

PMID- 19768369
TI  - Size frequency distribution of the beta-amyloid (abeta) deposits in dementia with
      Lewy bodies with associated Alzheimer's disease pathology.
AB  - The objective is to study beta-amyloid (Abeta) deposition in dementia with Lewy
      bodies (DLB) with Alzheimer's disease (AD) pathology (DLB/AD). The size frequency
      distributions of the Abeta deposits were studied and fitted by log-normal and
      power-law models. Patients were ten clinically and pathologically diagnosed
      DLB/AD cases. Size distributions had a single peak and were positively skewed and
      similar to those described in AD and Down's syndrome. Size distributions had
      smaller means in DLB/AD than in AD. Log-normal and power-law models were fitted
      to the size distributions of the classic and diffuse deposits, respectively. Size
      distributions of Abeta deposits were similar in DLB/AD and AD. Size distributions
      of the diffuse deposits were fitted by a power-law model suggesting that
      aggregation/disaggregation of Abeta was the predominant factor, whereas the
      classic deposits were fitted by a log-normal distribution suggesting that surface
      diffusion was important in the pathogenesis of the classic deposits.

PMID- 19768371
TI  - Syringomyelia associated with Chiari I malformation.
AB  - An 18-year-old man with progressive paraparesis, thermal hypoesthesia, sweating
      abnormalities, bladder dysfunction, severe orthostatic hypotension, bilateral
      Babinski sign, underwent a brain MRI scan that showed downward displacement of
      cerebellar tonsils through the foramen magnum, consistent with Chiari I
      malformation, compression of the brainstem-spinal cord junction, and C1-D11
      syringomyelia (6.5 mm diameter at C2 level) consistent with Chiari I syndrome.
      Suboccipital craniectomy and duraplasty were performed. A C2 partial laminectomy
      and ablation of posterior arch of the atlas was performed. MRI scans 4 days and 1
      month after surgery showed a dramatic syringomyelia reabsorption (2.5 and 1 mm,
      respectively) associated with complete clinical recovery.

PMID- 19768370
TI  - Neurosyphilis in the age of AIDS: clinical and laboratory features.
AB  - Neurosyphilis remains to be a challenging diagnostic possibility worldwide. The
      aim of our study was to identify and report the clinical and laboratory profile
      of neurosyphilis, comparing features of HIV-infected and HIV-negative patients. A
      retrospective investigation of all cases of neurosyphilis, defined as positive
      VDRL test on cerebrospinal fluid, diagnosed at Hospital das Clinicas, Ribeirao
      Preto School of Medicine between January 1988 and December 2005, was carried out.
      We identified 35 patients with a mean age of 42.1 years, 28.6% of them HIV
      infected and 74.3% of them were male. HIV-infected patients were younger (34.6
      years), presented with a higher frequency of the early forms of neurosyphilis,
      higher titers of serum VDRL and higher mean proteinorrachia at the suboccipital
      level. Neurosyphilis is still characterized by clinical polymorphism and there
      are significant differences in its epidemiological, clinical and laboratory
      profile when HIV-infected patients are compared with HIV-negative patients.

PMID- 19768372
TI  - Novel MAPT Val75Ala mutation and PSEN2 Arg62Hys in two siblings with
      frontotemporal dementia.
AB  - A clinical and molecular overlap between Alzheimer's disease (AD) and
      frontotemporal dementia (FTD) has been reported. Presenilins have been associated
      with FTD or with FTD-like phenotype, while mutations in the MAPT gene have been
      linked to a clinical phenotype of AD. We performed a clinical and genetic
      examination in two FTD siblings and their family tree has been reconstructed. We
      identified a novel Val75Ala MAPT mutation in one patient and in the other the
      Arg62His Presenilin2 mutation. The DNA variations identified, defined mutations
      by frequency, per se are not causative of the disease. These mutations, possibly
      in association with other unknown environmental and genetic factors, may
      contribute to neurodegeneration. In this family, the disease might result from a
      genetically interconnected spectrum of altered pathways that could link most
      neurodegenerative disorders. Moreover, the novel mutation identified merits
      further functional studies that would contribute to the unravelling of such a
      complex field.

PMID- 19768373
TI  - Self-help group and medication overuse headache: preliminary data.
AB  - The objective of the study is to investigate the benefits of joining a self-help
      group for patients with medication overuse headache (MOH). A self-help group is a
      voluntary gathering of a small number of persons who share a common problem.
      Little is known about support groups for people with chronic non-malignant pain
      such as MOH. Eight patients with refractory MOH attended a self-help group twice
      a month. During the meetings, patients were asked to focus on their headache
      experiences. Our data showed an increase in resourcefulness in coping with pain
      and a reduction in cephalalgiophobia. All patients reported general benefits in
      sharing their headache-related problems. No differences were found for headache
      frequency or analgesic overuse. To our knowledge, this is the first report on a
      self-help group for patients with MOH. Joining a self-help group can help
      patients develop positive attitudes to managing pain.

PMID- 19768374
TI  - Normative data for the Pyramids and Palm Trees Test in the elderly Italian
      population.
AB  - The Pyramids and Palm Tree Test (PPT) is a semantic memory test that measures the
      capacity to access detailed semantic information about words and pictures,
      necessary for the identification of the analogies, which link conceptually two
      perceptually, and functionally distinct entities. The present study aimed to
      provide normative data on a large sample of the elderly Italian population (N =
      464; range of age = 49-94; range of education = 3-25) on both the word and the
      picture versions of the PPT. Results from multiple regression analyses showed
      that both age and education were significant predictors of performance in both
      the word and the picture versions of the PPT. Therefore, norms were calculated
      taking into account these demographic variables. The availability of normative
      data based on a large sample will allow a more reliable use of the PPT for
      clinical assessment in Italian-speaking dementia population.

PMID- 19768375
TI  - Spinocerebellar ataxia type 11 in the Chinese Han population.
AB  - The spinocerebellar ataxias (SCAs) are a clinically and genetically heterogeneous
      group of neurodegenerative diseases. Researchers have recently found that SCA
      type 11 (SCA11) is associated with mutations in the TTBK2 gene. In our previous
      work, we performed mutation detection in SCA1, 2, 3, 6, 7, 8, 10, 12, 17 and
      dentatorubral-pallidoluysian atrophy gene in Chinese SCA patients, but the genes
      responsible for approximately 40% of our patients have not yet been identified.
      To investigate the frequency of SCA11 in Chinese SCA patients, we examined the
      TTBK2 gene in 68 unrelated probands diagnosed with dominantly inherited ataxia
      using the denaturing high-performance liquid chromatography method. All analyzed
      samples displayed the normal elution profile, which denoted that no disease
      related mutation was identified. We provided the evidence that SCA11 is a rare
      form of ataxia in China.

PMID- 19768376
TI  - Muscle carnitine deficiency: adult onset lipid storage myopathy with sensory
      neuropathy.
AB  - Muscle carnitine deficiency usually results in a lipid storage myopathy, but more
      rarely, neuropathy occurs in this condition. We report herein a 29-year-old man
      with muscle carnitine deficiency who developed not only a lipid storage myopathy,
      but also a severe sensory neuropathy. Oral therapy with levo-carnitine (3 g per
      day) for 3 months produced a remarkable improvement of the myopathy and sensory
      neuropathy. Six months later, he remained in good condition under strict dietary
      control. This report emphasizes that severe neuropathy may occur in some patients
      with muscle carnitine deficiency, and highlights the need for the neurologist's
      familiarity with those afflicted to achieve optimal clinical management.

PMID- 19768377
TI  - Irreversible striatal neuroimaging abnormalities secondary to prolonged,
      uncontrolled diabetes mellitus in the setting of progressive focal neurological
      symptoms.
AB  - Hemichorea-hemiballisum in patients with hyperglycemia and striatal
      hyperintensity on T1-weighted magnetic resonance imaging is now an accepted
      clinical entity. Usually, both the clinical syndrome and neuroimaging
      abnormalities are reversible. A transient, reversible metabolic impairment within
      the basal ganglion has been considered a possible cause of this disorder.
      However, the pathophysiology remains to be unclear. We report a 56-year-old man
      with a prolonged, uncontrolled hyperglycemia (HbA1C: 13.8%) and striatal
      hyperintensity on T1-weighted MR imaging presenting as reversible focal
      neurological deficit and irreversible neuroimaging abnormalities on the fourth
      month when blood sugar was under control (HbA1C 6.0 mg/dl). We hypothesize that
      neuroimaging abnormalities in our case may be a sequence of an "ischemic insult"
      caused by prolonged, uncontrolled hyperglycemia. Whether the signal abnormalities
      on neuroimaging studies or the clinical syndrome are reversible (patients with
      HCHB) or irreversible (such as in our case) are based on the degree of ischemic
      damage.

PMID- 19768378
TI  - Myeloneuropathy due to copper deficiency: clinical and MRI findings after copper
      supplementation.
AB  - Acquired copper deficiency constitutes an under-recognised cause of myelopathy.
      Aim of the study was to describe the clinical and imaging features at admission
      and after copper supplementation of a patient with acquired copper deficiency
      myeloneuropathy. A 73-year-old woman presented with anaemia and signs of
      posterior column dysfunction. Somatosensory evoked potentials showed impaired
      central pathway conduction. Serum copper and caeruloplasmin levels were low.
      Nerve conduction assessment revealed axonal polyneuropathy. Spinal magnetic
      resonance imaging (MRI) showed posterior column hyperintensity. Diffusion tensor
      imaging disclosed decreased fractional anisotropy (FA) corresponding to the
      hyperintensity. Copper supplementation normalised the haematological picture,
      whereas vibratory sensitivity was only slightly improved. Control MRI revealed a
      slight hyperintensity at C1-C2 level; FA values normalised. In conclusion, in
      acquired copper-deficiency-associated myelopathy, correction of blood and MRI
      alterations precedes that of neurological manifestations, which may remain
      suboptimal.

PMID- 19768379
TI  - An influenza A H1N1 virus revival - pandemic H1N1/09 virus.
AB  - In April 2009, a novel H1N1 influenza A virus, the so-called pandemic H1N1/09
      virus (former designations include swine influenza, novel influenza, swine-origin
      influenza A [H1N1] virus [S-OIV], Mexican flu, North American Flu) was identified
      in Mexico. The virus has since spread throughout the world and caused an
      influenza pandemic as defined by the criteria of the World Health Organization.
      This represents the first influenza A virus pandemic since the emergence of H3N2
      (''Hong Kong'' Flu) in 1968. Vaccine production has started, and vaccines are
      expected to become available during the course of 2009. Although the pandemic
      H1N1/09 virus originates from the triple-reassortant swine influenza (H1) virus
      circulating in North American pigs, it is not epidemic in pigs. Although the
      H1N1/09 virus pandemic is currently mild, concerns remain that it may become more
      aggressive during spreading. The distribution of proper information to the public
      on the status of the H1N1/09 virus pandemic will be important to achieve a broad
      awareness of the potential risks and the optimum code of behavior during the
      pandemic. Here, the features of pandemic H1N1/09 virus are discussed within the
      framework of knowledge gained from previous influenza A virus pandemics.

PMID- 19768380
TI  - Carbapenem-resistant Acinetobacter baumannii producing the OXA-23 enzyme:
      dissemination in Southern Brazil.

PMID- 19768382
TI  - Disparities in influenza vaccination coverage rates by target group in five
      European countries: trends over seven consecutive seasons.
AB  - BACKGROUND: The primary objective of this study was to measure influenza
      vaccination coverage rates in the general population, including children, and in
      high-risk groups of five European countries during the season 2007/2008. An
      additional aim was to analyze coverage trends over seven consecutive seasons and
      to gain an understanding of the primary drivers and barriers to immunization.
      METHODS: Community-based telephone and mail surveys have been conducted in the
      UK, Germany, Italy, France, and Spain, yearly, since 2001/2002. Approximately
      2,000 individuals per country and season were interviewed who were considered to
      be representative of the adult population aged 14 years and older. Data on the
      vaccination status of children were obtained by proxy interviews. The
      questionnaire used was essentially the same for all seven seasons. Five target
      groups were identified for the study: (1) persons aged > or = 65 years; (2)
      elderly suffering from a chronic illness; (3) patients suffering from a chronic
      illness; (4) persons working in the health care sector; (5) children. RESULTS: In
      the season 2007/2008, vaccination coverage rates in the general population
      remained stable in Germany. Compared to the coverage rates of the previous
      season, increases of 3.7%, 2.0%, and 1.8% were observed for the UK, Spain, and
      France, respectively, while a decrease of -1.5% was observed for Italy. Across
      all five countries, vaccination rates in the predefined target groups decreased
      to some extent (elderly) or increased slightly (chronically ill and health care
      workers). Vaccination rates among children varied strongly between countries and
      ranged from 6.1% in UK to 19.3% in Germany. The most powerful motivation for
      getting vaccinated in all countries was advice from a family doctor (58.6%) and
      the perception of influenza as a serious illness (51.9%). The major reasons why
      individuals did not become vaccinated were (1) the feeling of not being likely to
      catch influenza (39.5%) and (2) never having considered the option of being
      vaccinated (35.8%). CONCLUSIONS: The change in general influenza vaccination
      coverage in the 2007/2008 season compared to the previous season was small, but
      decreases were seen in some target groups. The underlying motivations for and
      against vaccination did not substantially change. An effort to activate those
      driving forces that would encourage vaccination as well as dealing with barriers
      that tend to prevent it may help enhance coverage rates in Europe in the future.

PMID- 19768381
TI  - Efficacy and safety of sequential intravenous/oral moxifloxacin vs
      intravenous/oral amoxicillin/clavulanate for complicated skin and skin structure
      infections.
AB  - BACKGROUND: Complicated skin and skin structure infections (cSSSIs) are an
      important healthcare concern worldwide, as they can be life-threatening and
      challenging to treat. cSSSIs are normally managed using a combination of surgical
      intervention and prompt antibiotic use. New therapeutic options, including novel
      antibiotics, are required to improve outcomes in terms of duration of illness and
      to reduce the consumption of healthcare resources. METHODS: This was a
      prospective, randomized, open-label, parallel-group, multinational clinical study
      comparing sequential intravenous/oral (iv/po) moxifloxacin, 400 mg once daily,
      and iv amoxicillin/clavulanate, 1,000 mg/ 200 mg three times daily followed by po
      amoxicillin/ clavulanate, 500 mg/125 mg three times daily, for 7-21 days in
      hospitalized patients. RESULTS: A total of 804 patients were enrolled (mean age
      51.8 years). The most common clinical diagnosis was complicated erysipelas (32.1%
      moxifloxacin; 30.0% amoxicillin/ clavulanate) and major abscess (31.1%
      moxifloxacin; 29.3% amoxicillin/clavulanate). Overall clinical success rates at
      the test-of-cure (TOC) visit (14-28 days post-treatment) for the per-protocol
      population (primary efficacy variable) were 80.6% (254/315) for patients in the
      moxifloxacin group and 84.5% (268/317) for those receiving
      amoxicillin/clavulanate (95% confidence interval [CI] -9.41, 2.18). Similar
      results were obtained for the intention-to-treat population (95% CI -7.56, 4.31).
      In both treatment groups, the highest clinical success rates were recorded for
      patients with complicated erysipelas, major abscess, surgical wound infection,
      and cellulitis. The lowest clinical cure rates were reported for diabetic foot
      infection and necrotizing fasciitis. In the microbiologically evaluable
      population, the bacteriological success rate (eradication and presumed
      eradication) was 76.0% (127/ 167) in the moxifloxacin group and 81.4% (140/172)
      in the amoxicillin/clavulanate group (95% CI -12.96, 4.41). Staphylococcus aureus
      (137 isolates) and Escherichia coli (50 isolates) were the most frequently
      isolated skin pathogens. Adverse event rates were comparable between treatment
      groups. CONCLUSIONS: Treatment with sequential iv/po moxifloxacin monotherapy
      once daily is clinically comparable to that with iv/po amoxicillin/clavulanate
      three times daily in the management of cSSSIs. Moxifloxacin's simple dose regimen
      offers an advantage over amoxicillin/clavulanate and represents a valuable
      addition to current antibiotic regimens used in the treatment of cSSSIs.

PMID- 19768383
TI  - Against the new H1N1 influenza (swine influenza): vaccinate or don't vaccinate
      (all)? That is currently the question!

PMID- 19768384
TI  - Landscape and well-being: a scoping study on the health-promoting impact of
      outdoor environments.
AB  - OBJECTIVES: The present literature review conceptualises landscape as a health
      resource that promotes physical, mental, and social well-being. Different health
      promoting landscape characteristics are discussed. METHODS: This article is based
      on a scoping study which represents a special kind of qualitative literature
      review. Over 120 studies have been reviewed in a five-step-procedure, resulting
      in a heuristic device. RESULTS: A set of meaningful pathways that link landscape
      and health have been identified. Landscapes have the potential to promote mental
      well-being through attention restoration, stress reduction, and the evocation of
      positive emotions; physical well-being through the promotion of physical activity
      in daily life as well as leisure time and through walkable environments; and
      social well-being through social integration, social engagement and
      participation, and through social support and security. CONCLUSION: This scoping
      study allows us to systematically describe the potential of landscape as a
      resource for physical, mental and social well-being. A heuristic framework is
      presented that can be applied in future studies, facilitating systematic and
      focused research approaches and informing practical public health interventions.

PMID- 19768385
TI  - Suppression of ongoing experimental autoimmune myasthenia gravis by transfer of
      RelB-silenced bone marrow dentritic cells is associated with a change from a T
      helper Th17/Th1 to a Th2 and FoxP3+ regulatory T-cell profile.
AB  - OBJECTIVE: To observe the therapeutic effect of RelB-silenced dendritic cells
      (DCs) in experimental autoimmune myasthenia gravis (EAMG), and further to
      investigate the mechanism of this immune system therapeutic. METHODS: (1) RelB
      silenced DCs and control DCs were prepared and the supernatants were collected
      for IL-12p70, IL-6, and IL-23 measurement by ELISA. (2) RelB-silenced DCs and
      control DCs were co-cultured with AChR-specific T cells, and the supernatant was
      collected to observe the IL-17, IFN-gamma, IL-4 production. (3) EAMG mice with
      clinical scores of 1 to 2 were collected and enrolled randomly into the RelB
      silenced DC group or the control DC group. RelB-silenced DCs or an equal amount
      of control DCs were injected intravenously on days 0, 7, and 14 after enrollment.
      Clinical scores were evaluated every other day. Twenty days after allotment,
      serum from individual mice was collected to detect serum concentrations of anti
      mouse AChR IgG, IgG1, IgG2b, and IgG2c. The splenocytes were isolated for
      analysis of lymphocyte proliferative responses, cytokine (IL-17, IFN-gamma, IL-4)
      production, and protein levels of RORgammat, T-bet, GATA-3, and FoxP3 (the
      special transcription factors of Th17, Th1, Th2, and Treg, respectively).
      RESULTS: (1) RelB-silenced DCs produced significantly reduced amounts of IL
      12p70, IL-6, and IL-23, as compared with control DCs. (2) RelB-silenced DCs
      spurred on the CD4(+) T cells from Th1/Th17 to the Th2 cell subset in the co
      culture system. (3) Treatment with RelB-silenced DCs effectively reduced
      myasthenic symptoms and levels of serum anti-acetylcholine receptor autoantibody
      in mice with ongoing EAMG. Th17-related markers (RORgammat, IL-17) and Th1
      related markers (T-bet, IFN-gamma) were downregulated, whereas Th2 markers (IL-4
      and GATA3) and Treg marker (FoxP3) were upregulated. CONCLUSIONS: RelB-silenced
      DCs were able to create a particular cytokine environment that was absent of
      inflammatory cytokines. RelB-silenced DCs provide a practical means to normalize
      the differentiation of the four T-cell subsets (Th17, Th1, Th2, and Treg) in
      vivo, and thus possess therapeutic potential in Th1/Th17-dominant autoimmune
      disorders such as myasthenia gravis.

PMID- 19768386
TI  - Intratumoral concentrations of imatinib after oral administration in patients
      with glioblastoma multiforme.
AB  - Imatinib, an orally administered tyrosine kinase inhibitor of PDGF receptor, c
      abl and c-kit, is currently in clinical trials to assess its efficacy in
      malignant gliomas. Although imatinib does not readily penetrate an intact blood
      brain barrier (BBB), the extent to which it distributes into regions of high
      grade gliomas where the BBB is compromised has not been determined. Patients with
      recurrent high-grade gliomas for whom repeat surgical tumor debulking was
      clinically indicated received imatinib mesylate 600 mg orally once a day for
      seven days prior to surgery. Tissue samples were collected from different regions
      of the tumor and the approximate location of these samples was determined using
      frameless stereotactic neuronavigation. Plasma samples were obtained immediately
      before and after the resection. The concentration of imatinib in the plasma and
      tumor samples was determined using high performance liquid chromatography with
      mass spectrometric detection. Eleven tumor samples were obtained from three
      patients with recurrent glioblastoma multiforme. The median concentration of
      imatinib in these 11 tumor specimens was 1.34 microg/g (range 0.21-4.31 microg/g)
      and the median tumor-to-plasma ratio was 0.71 (range 0.28-3.03). These findings
      suggest that imatinib can reach intratumoral concentrations similar to those or
      higher than in plasma in regions of glioblastoma where the BBB is disrupted as
      indicated by contrast enhancement on magnetic resonance imaging.

PMID- 19768387
TI  - An intraresidual i(HCA)CO(CA)NH experiment for the assignment of main-chain
      resonances in 15N, 13C labeled proteins.
AB  - An improved pulse sequence, intraresidual i(HCA)CO(CA)NH, is described for
      establishing solely (13)C'(i), (15)N(i), (1)HN(i) connectivities in uniformly
      15N/13C-labeled proteins. In comparison to the "out-and-back" style intra
      HN(CA)CO experiment, the new pulse sequence offers at least two-fold higher
      experimental resolution in the (13)C' dimension and on average 1.6 times higher
      sensitivity especially for residues in alpha-helices. Performance of the new
      experiment was tested on a small globular protein ubiquitin and an intrinsically
      unfolded 110-residue cancer/testis antigen CT16/PAGE5. Use of intraresidual
      i(HCA)CO(CA)NH experiment in combination with the established HNCO experiment was
      crucial for the assignment of highly disordered CT16.

PMID- 19768388
TI  - A process to produce penicillin G acylase by surface-adhesion fermentation using
      Mucor griseocyanus to obtain 6-aminopenicillanic acid by penicillin G hydrolysis.
AB  - The production of extracellular and mycelia-associated penicillin G acylase
      (maPGA) with Mucor griseocyanus H/55.1.1 by surface-adhesion fermentation using
      Opuntia imbricata, a cactus, as a natural immobilization support was studied.
      Enzyme activity to form 6-aminopencillanic acid (6-APA) from penicillin G was
      assayed spectrophotometrically. The penicillin G hydrolysis to 6-APA was
      evaluated at six different times using PGA samples recovered from the skim milk
      medium at five different incubation times. Additionally, the effect of varying
      the penicillin G substrate concentration level on the PGA enzyme activity was
      also studied. The maximum reaction rate, V (max), and the Michaelis constant, K
      (M), were determined using the Michaelis-Menten model. The maximum levels for
      maPGA and extracellular activity were found to be 2,126.50 international unit per
      liter (IU/l; equal to 997.83 IU/g of support) at 48 h and 755.33 IU/l at 60 h,
      respectively. Kinetics of biomass production for total biomass showed a maximum
      growth at 60 h of 3.36 and 2.55 g/l (equal to 0.012 g of biomass per gram of
      support) for the immobilized M. griseocyanus biomass. The maPGA was employed for
      the hydrolysis of penicillin G to obtain 6-APA in a batch reactor. The highest
      quantity of 6-APA obtained was 226.16 mg/l after 40-min reaction. The effect of
      substrate concentration on maPGA activity was evaluated at different
      concentrations of penicillin G (0-10 mM). K(M) and V(max) were determined to be
      3.0 x 10(-3) M and 4.4 x 10(-3) mM/min, respectively.

PMID- 19768389
TI  - Microwave exposure affecting reproductive system in male rats.
AB  - The object of present study is to investigate the effects of 50 GHz microwave
      frequency electromagnetic fields on reproductive system of male rats. Male rats
      of Wistar strain were used in the study. Animals 60 days old were divided into
      two groups--group I sham exposed and group II experimental (microwave exposed).
      During exposure, rats were confined in Plexiglas cages with drilled ventilation
      holes for 2 h a day for 45 days continuously at a specified specific absorption
      rate of 8.0 x 10(-4) W/kg. After the last exposure, the rats were sacrificed
      immediately and sperms were collected. Antioxidant enzyme (superoxide dismutase
      (SOD), glutathione peroxidase (GPx), and catalase), histone kinase, apoptosis,
      and cell cycle were analyzed in sperm cells. Result shows a significant decrease
      in the level of sperm GPx and SOD activity (p < or = 0.05), whereas catalase
      shows significant increase in exposed group of sperm samples as compared with
      control (p < 0.02). We observed a statistically significant decrease in mean
      activity of histone kinase as compared to the control (p < 0.016). The percentage
      of cells dividing in a spermatogenesis was estimated by analyzing DNA per cell by
      flow cytometry. The percentage of apoptosis in electromagnetic field exposed
      group shows increased ratio as compared to sham exposed (p < 0.004). There were
      no significant differences in the G(0)/G(1) phase; however, a significant
      decrease (p < 0.026) in S phase was obtained. Results also indicate a decrease in
      percentage of G(2)/M transition phase of cell cycle in exposed group as compared
      to sham exposed (p < 0.019). We conclude that these radiations may have a
      significant effect on reproductive system of male rats, which may be an
      indication of male infertility.

PMID- 19768390
TI  - [Obligatory vaccination reporting in Saxony-Anhalt. Possibilities and limitations
      of establishing a computerized vaccination registry].
AB  - Vaccination registries are databases intended to assess and manage complete
      vaccination data of as many individuals as possible in a population under survey.
      The task of these registries is to identify low vaccination rates on the
      individual and population level, to enable systems of reminding individuals, to
      focus vaccination campaigns and to maximize overall vaccination coverage. Saxony
      Anhalt is the only federal state of Germany to have a law that prescribes the
      reporting of vaccinations. Vaccinations of children up to the age of 7 are
      reported to the regional public health services. However, as the law provides no
      regulations as to how the data should be registered and processed, the
      development of a vaccination registry depends entirely on the initiative and
      cooperation of the "players in vaccination". The key players in vaccination in
      Saxony-Anhalt have recently created a Vaccination-Committee, which set out to
      develop the theoretical standards and a software prototype for the establishment
      of a computerized vaccination registry. Recent developments in the public health
      reporting system of Saxony-Anhalt (which strives to modernize its computerized
      assessment of child and adolescent health) are now opening the possibility to
      integrate the vaccination registry into the commercially available child health
      software.

PMID- 19768391
TI  - [Vaccination recommendations of the Standing Committee on Vaccination at the
      Robert Koch Institute. Legal basis and significance].
AB  - The promotion of immunisation in Germany is regulated under Federal and Land
      (state) law. The Protection against Infection Act (Infektionsschutzgesetz)
      provides the framework for immunisations as a means of public health protection
      from vaccine-preventable diseases. Book Five of the Social Code (SGB V) regulates
      the claim of statutory health insurance members to receive protective
      vaccinations. Both federal laws stipulate that the health administration and the
      self-administration organs proceed on the basis of the recommendations issued by
      the Standing Committee on Vaccination (STIKO) at the Robert Koch Institute. This
      ensures homogeneous, evidence-based and comprehensive preventive immunisation
      coverage and the provision of the corresponding benefits by the statutory health
      insurance. In the Laender (states), the tasks and possibilities of the public
      health services vary with respect to preventive immunisations. A future task will
      be to further intensify cooperation among the institutions of self-administration
      in the health care system and the authorities at the local, Land (state) and
      Federal levels. Concerted action can achieve an increase in immunisation
      participation by the population, especially in regions where levels are moderate.

PMID- 19768392
TI  - [Development and implementation of health targets for children and adolescents.
      What contribution can the Robert Koch Institute's National Health Interview and
      Examination Survey for Children and Adolescents (KiGGS) make?].
AB  - Health targets are increasingly becoming a health-policy control instrument, both
      nationally and internationally. In the project gesundheitsziele.de, targets have
      been formulated for children and adolescents in Germany - currently in the areas
      of nutrition, exercise, and stress management. Implementing and evaluating health
      targets requires regularly updated, informative data that allow a comprehensive
      and precise description of the relevant problems and developments. The Robert
      Koch Institute's National Health Interview and Examination Survey for Children
      and Adolescents - conducted during the period from 2003 to 2006 - provides a pool
      of data with information on virtually all facets of health development during
      childhood and adolescence which can be used to determine the starting point of
      the health-targeting process. This article describes the data provided by the
      survey of the areas nutrition, exercise, and stress management and the
      contribution these data could make towards further developing and implementing
      the health targets for children and adolescents.

PMID- 19768393
TI  - [Evaluating the health target "Increasing health competence,   strengthening
      patient sovereignty"].
AB  - Establishing citizen and patient orientation is a national objective of German
      health policy. The cooperation network gesundheitsziele.de has defined the target
      area "Increasing health competence, strengthening patient sovereignty", and its
      Working Group 8, which bears the same name, has identified four key areas for
      action: increasing transparency, developing competence, strengthening patients'
      rights, and improving complaint management. As in the case of all the other
      targets defined by gesundheitsziele.de, attention is drawn to the need to
      evaluate the effects and success of the targets and related measures. A group of
      experts was given the task of developing an evaluation strategy, defining success
      indicators, and examining the availability of data sources for evaluation. With
      regard to the health target "Increasing health competence, strengthening patient
      sovereignty", the evaluation is focusing on what effect the corresponding targets
      and measures are having on users and how they are perceived (summative
      evaluation), i.e., primarily on measuring outcomes at the population level. An
      examination of available studies and surveys shows that to date little is known
      about the expectations and assessments of health-service users. At the same time,
      the analysis makes it clear that priority should be given to using continuous
      data in order to arrive at a continuous and systematic evaluation of the
      "Increasing health competence, strengthening patient sovereignty" health target
      and the implementation of citizen and patient orientation in healthcare in
      general. It would also be useful to include all hitherto underrepresented
      indicator questions in these surveys and to also examine the implementation of
      the health target among vulnerable population groups, e.g., elderly people in
      nursing homes.

PMID- 19768394
TI  - [Therapy-resistant tibial pseudarthrosis. Treatment success with BMP-7 combined
      with autologous bone].
AB  - Delayed union or non-union of long bone shaft fractures still presents a surgical
      challenge. Especially if there is a predisposition for pseudarthrosis such as
      adiposity, diabetes mellitus, local disruption of blood supply or lack of
      hormones, the established procedures of autologous cancellous bone grafting or
      plate fixation with compression often lead to insufficient results. In the
      following article the successful use of bone morphogenetic protein BMP-7
      [recombinant human osteogenetic protein-1 (rhOP-1)], combined with autologous
      bone grafting for therapy of a therapy-resistant tibial non-union is described.
      In a patient with multiple risk factors the tibial fracture was completely cured
      after two attempts of osteosynthesis and autologous bone grafting had failed. The
      patient achieved self-mobility with full weight bearing and absence of pain 10
      months after adjuvant implantation of BMP-7.

PMID- 19768395
TI  - A role for succinate dehydrogenase genes in low chemoresponsiveness to hypoxia?
AB  - The detection of hypoxia by the carotid bodies elicits a ventilatory response of
      utmost importance for tolerance to high altitude. Germline mutations in three
      genes encoding subunit B, C and D of succinate dehydrogenase (SDHB, SDHC and
      SDHD) have been associated with paragangliomas of the carotid body. We
      hypothesized that SDH dysfunction within the carotid body could result in low
      chemoresponsiveness and intolerance to high altitude. The frequency of
      polymorphisms of SDHs, hypoxia-inducible factor type 1 (HIF1alpha) and
      angiotensin converting enzyme (ACE) genes was compared between 40 subjects with
      intolerance to high altitude and a low hypoxic ventilatory response at exercise
      (HVRe < or = 0.5 ml min(-1) kg(-1); HVR- group) and 41 subjects without
      intolerance to high altitude and a high HVRe (> or = 0.80 ml min(-1) kg(-1);
      HVR+). We found no significant association between low or high HVRe and (1) the
      allele frequencies for nine single nucleotide polymorphisms (SNPs) in the SDHD
      and SDHB genes, (2) the ACE insertion/deletion polymorphism and (3) four SNPs in
      the HIF1alpha gene. However, a marginal significant association was found between
      the synonymous polymorphism c.18A>C of the SDHB gene and chemoresponsiveness:
      8/40 (20%) in the HVR- group and 3/41 (7%) in the HVR+ group (p = 0.12). A
      principal component analysis showed that no subject carrying the 18C allele had
      both high ventilatory and cardiac response to hypoxia. In conclusion, no clear
      association was found between gene variants involved in oxygen sensing and
      chemoresponsiveness, although some mutations in the SDHB and SDHD genes deserve
      further investigations in a larger population.

PMID- 19768396
TI  - Effect of the Ca/P ratio on the dielectric properties of nanoscaled
      substoichiometric hydroxyapatite.
AB  - Nanoscaled hydroxyapatite (n-HAp) was prepared by a wet chemical precipitation
      method, pressed to pellets and sintered at various temperatures between 900 and
      1200 degrees C. With input stoichiometries of Ca/P ratios between 1.4 and 2.0,
      compositions in the substoichiometric range of Ca/P between 1.45(1) and 1.62(3)
      were determined after preparation. After sintering, final values of the Ca/P
      ratio between 1.45(8) and 1.66(4) were found. Capacitances and dielectric losses
      were determined in the frequency range between 20 Hz and 1 MHz and dielectric
      constants calculated from the capacitances. Dependencies of the dielectric
      properties on the composition, as well as on sintering temperature and
      frequencies were investigated. The dielectric constants generally tend to
      increase with increasing Ca-content. Different behaviour was observed for low
      frequencies (below 10(3) Hz) and for compositions far from the stoichiometric
      point of hydroxyapatite (Ca/P: 1.67). Comparable results were found for
      dielectric losses.

PMID- 19768397
TI  - Selected physicochemical properties of the experimental endodontic sealer.
AB  - This study explores water sorption, hygroscopic expansion, mechanical strength
      and ion release from the experimental amorphous calcium phosphate (ACP)
      composites formulated for application as endodontic sealers. Light-cure (LC) and
      dual-cure (DC; combined light and chemical cure) resins comprised urethane
      dimethacrylate (UDMA), 2-hydroxyethyl methacrylate (HEMA), methacryloyloxyethyl
      phthalate (MEP) and a high molecular mass oligomeric co-monomer,
      poly(ethyleneglycol)-extended UDMA (PEG-U) (designated UPHM resin). To fabricate
      composites, a mass fraction of 60% UPHM resin was blended with a mass fraction of
      40% as-made (am-) or ground (g-) ACP. Glass-filled composites were used as
      controls. Both DC and LC ACP UPHM composites exhibited relatively high levels of
      water sorption accompanied by a significant hygroscopic expansion. The latter may
      potentially be useful to offset high polymerization stresses that develop in
      these materials. Ion release profiles of the experimental materials confirmed
      their potential for regeneration of mineral-deficient tooth structures. Their
      moderate to low mechanical strength after 3 months of aqueous immersion did not
      diminish the enthusiasm for the proposed use as endodontic sealers. For that
      application, DC g-ACP composites appear to be the most adequate, but micro
      leakage and quantitative leachability studies are needed to fully establish their
      suitability.

PMID- 19768398
TI  - Pandemic influenza as a current threat.
AB  - Pandemics of influenza emerge from the aquatic bird reservoir, adapt to humans,
      modify their severity, and cause seasonal influenza. The catastrophic Spanish
      H1N1 virus may have obtained all of its eight gene segments from the avian
      reservoir, whereas the Asian H2N2 and the Hong Kong H3N2 pandemics emerged by
      reassortment between the circulating human virus and an avian H2 or H3 donor. Of
      the 16 hemagglutinin subtypes, the H2, H5, H6, H7, and H9 viruses are considered
      to have pandemic potential. While this chapter focuses on the evolution of the
      Asian highly pathogenic (HP) H5N1 influenza virus, other subtypes are also
      considered. The unique features of the HP H5N1 viruses that have devastated the
      domestic poultry of Eurasia are discussed. Although they transmit poorly to
      humans, they continue to kill more than 60% of infected persons. It is unknown
      whether HP H5N1 will acquire human pandemic status; if it does not, another
      subtype eventually will do so, for a future influenza pandemic is inevitable.

PMID- 19768399
TI  - Antigenic cross-reactivity among H5N1 viruses.
AB  - The unprecedented spread of highly pathogenic H5N1 viruses since 1996 has had
      public health and scientific entities scrambling to prepare for a possible
      pandemic. Central to many of these efforts has been the development of vaccines.
      As the viruses have continued to spread, however, they have continued to
      diversify genetically, complicating vaccine strain selection. The key to
      successful vaccine design is understanding the cross-reactivity between these
      genetically distinct H5N1 strains. Studies conducted to date show encouraging
      amounts of cross-reaction and cross-protection between various H5N1 strains,
      although our ability to predict one based upon the other is poor. Understanding
      the targets and mechanisms behind this cross-protection should be a key focus of
      pandemic preparedness.

PMID- 19768400
TI  - Seasonal influenza vaccines.
AB  - Influenza vaccines are the mainstay of efforts to reduce the substantial health
      burden from seasonal influenza. Inactivated influenza vaccines have been
      available since the 1940s and are administered via intramuscular injection.
      Inactivated vaccines can be given to anyone six months of age or older. Live
      attenuated, cold-adapted influenza vaccines (LAIV) were developed in the 1960s
      but were not licensed in the United States until 2003, and are administered via
      nasal spray. Both vaccines are trivalent preparations grown in eggs and do not
      contain adjuvants. LAIV is licensed for use in the United States for healthy
      nonpregnant persons 2-49 years of age.Influenza vaccination induces antibodies
      primarily against the major surface glycoproteins hemagglutinin (HA) and
      neuraminidase (NA); antibodies directed against the HA are most important for
      protection against illness. The immune response peaks at 2-4 weeks after one dose
      in primed individuals. In previously unvaccinated children <9 years of age, two
      doses of influenza vaccine are recommended, as some children in this age group
      have limited or no prior infections from circulating types and subtypes of
      seasonal influenza. These children require both an initial priming dose and a
      subsequent booster dose of vaccine to mount a protective antibody response.The
      most common adverse events associated with inactivated vaccines are sore arm and
      redness at the injection site; systemic symptoms such as fever or malaise are
      less commonly reported. Guillian-Barre Syndrome (GBS) was identified among
      approximately 1 per 100,000 recipients of the 1976 swine influenza vaccine. The
      risk of influenza vaccine-associated GBS from seasonal influenza vaccine is
      thought to be at most approximately 1-2 cases per 1 million vaccinees, based on a
      few studies that have found an association; other studies have found no
      association.The most common adverse events associated with LAIV are nasal
      congestion, headache, myalgias or fever. Studies of the safety of LAIV among
      young children suggest an increased risk of wheezing in some young children, and
      the vaccine is not recommended for children younger than 2 years old, ages 2-4
      old with a history of recurrent wheezing or reactive airways disease, or older
      persons who have any medical condition that confers an increased risk of
      influenza-related complications.The effectiveness of influenza vaccines is
      related predominantly to the age and immune competence of the vaccinee and the
      antigenic relatedness of vaccine strains to circulating strains. Vaccine
      effectiveness in preventing laboratory-confirmed influenza illness when the
      vaccine strains are well matched to circulating strains is 70-90% in randomized,
      placebo-controlled trials conducted among children and young healthy adults, but
      is lower among elderly or immunocompromised persons. In years with a suboptimal
      match, vaccine benefit is likely to be lower, although the vaccine can still
      provide substantial benefit, especially against more severe outcomes. Live,
      attenuated influenza vaccines have been most extensively studied among children,
      and have been shown to be more effective than inactivated vaccines in several
      randomized controlled trials among young children.Influenza vaccination is
      recommended in the United States for all children six months or older, all adults
      50 years or older, all persons with chronic medical conditions, and pregnant
      women, and contacts of these persons, including healthcare workers. The global
      disease burden of influenza is substantial, and the World Health Organization has
      indicated that member states should evaluate the cost-effectiveness of
      introducing influenza vaccination into national immunization programs. More
      research is needed to develop more effective seasonal influenza vaccines that
      provide long-lasting immunity and broad protection against strains that differ
      antigenically from vaccine viruses.

PMID- 19768401
TI  - Generation and characterization of candidate vaccine viruses for prepandemic
      influenza vaccines.
AB  - Vaccination will be a critical public health intervention to mitigate the next
      influenza pandemic. Its effectiveness will depend on preparedness at multiple
      levels, from the laboratory bench to the population. Here we describe a global
      approach to ensure that appropriate candidate vaccine viruses are produced,
      evaluated, and made available to vaccine manufacturers in a timely fashion. This
      is an integrated activity involving global virologic and epidemiologic
      surveillance, genetic and antigenic characterization of influenza viruses,
      pandemic risk assessments, selection of appropriate virus strains for vaccines,
      production of reassortant viruses by reverse genetics, and finally, analysis of
      their safety and growth characteristics prior to distribution. These procedures
      must comply with national and international regulations governing vaccine and
      environmental safety.

PMID- 19768402
TI  - Live attenuated vaccines for pandemic influenza.
AB  - In this chapter, we will review the development of and clinical experience with
      the currently licensed seasonal live attenuated influenza vaccines (LAIV) and
      preclinical studies of H5, H7, and H9 live attenuated pandemic influenza vaccine
      candidates. Vectored vaccine approaches will not be reviewed in this chapter.
      Experience with seasonal influenza vaccination has demonstrated the safety and
      efficacy of LAIV in both children and adults; moreover, cross-protection among
      antigenically distinct viruses within the same subtype may be induced by LAIV.
      While clinical studies and further characterization of the immunologic response
      to avian influenza viruses are still needed, the experience with seasonal LAIV
      underscores the potential of live attenuated vaccines to play an important role
      in the event of a pandemic.

PMID- 19768403
TI  - Influenza vaccines for avian species.
AB  - Beginning in Southeast Asia in 2003, a multinational epizootic outbreak of H5N1
      highly pathogenic avian influenza (HPAI) was identified in commercial poultry and
      wild bird species. This lineage, originally identified in Southern China in 1996
      and then Hong Kong in 1997, caused severe morbidity and mortality in many bird
      species, was responsible for considerable economic losses via trade restrictions,
      and crossed species barriers (including its recovery from human cases). To date,
      these H5N1 HPAI viruses have been isolated in European, Middle Eastern, and
      African countries, and are considered endemic in many areas where regulatory
      control and different production sectors face substantial hurdles in controlling
      the spread of this disease. While control of avian influenza (AI) virus
      infections in wild bird populations may not be feasible at this point, control
      and eradiation of AI from commercial, semicommercial, zoo, pet, and
      village/backyard birds will be critical to preventing events that could lead to
      the emergence of epizootic influenza virus. Efficacious vaccines can help reduce
      disease, viral shedding, and transmission to susceptible cohorts. However, only
      when vaccines are used in a comprehensive program including biosecurity,
      education, culling, diagnostics and surveillance can control and eradication be
      considered achievable goals. In humans, protection against influenza is provided
      by vaccines that are chosen based on molecular, epidemiologic, and antigenic
      data. In poultry and other birds, AI vaccines are produced against a specific
      hemagglutinin subtype of AI, and use is decided by government and state
      agricultural authorities based on risk and economic considerations, including the
      potential for trade restrictions. In the current H5N1 HPAI epizootic, vaccines
      have been used in a variety of avian species as a part of an overall control
      program to aid in disease management and control.

PMID- 19768404
TI  - Development and application of avian influenza vaccines in China.
AB  - Following the first detection of the highly pathogenic H5N1 avian influenza virus
      in sick geese in Guangdong Province in China in 1996, scientists began to develop
      vaccines in preparation for an avian influenza pandemic. An inactivated H5N2
      vaccine was produced from a low pathogenic virus, A/turkey/England/N-28/73, and
      was used for buffer zone vaccination during H5N1 outbreaks in 2004 in China. We
      also generated a low pathogenic H5N1 reassortant virus (Re-1) that derives its HA
      and NA genes from the GS/GD/96 virus and six internal genes from the high-growth
      A/Puerto Rico/8/34 (PR8) virus using plasmid-based reverse genetics. The
      inactivated vaccine derived from the Re-1 strain could induce more than ten
      months of protective immunity in chickens after one-dose inoculation; most
      importantly, this vaccine is immunogenic for geese and ducks. We recently
      developed a Newcastle virus-vectored live vaccine that exhibits great promise for
      use in the field to prevent highly pathogenic avian influenza and Newcastle
      disease in chickens. Over 30 billion doses of these vaccines have been used in
      China and other countries, including Vietnam, Mongolia, and Egypt, and have
      played an important role in H5N1 avian influenza control in these countries.

PMID- 19768405
TI  - Designing vaccines for pandemic influenza.
AB  - Recent outbreaks of highly pathogenic avian influenza A virus infections
      (including those of the H5N1 subtype) in poultry and in humans (through contact
      with infected birds) have raised concerns that a new influenza pandemic will soon
      occur. Effective vaccines against H5N1 virus are therefore urgently needed.
      Reverse genetics-based inactivated vaccines have been prepared according to WHO
      recommendations and licensed in several countries following their assessment in
      clinical trials. However, the effectiveness of these vaccines in a pandemic is
      not guaranteed. We must therefore continue to develop alternative pandemic
      vaccine strategies. Here, we review the current strategies for the development of
      H5N1 influenza vaccines, as well as some future directions for vaccine
      development.

PMID- 19768406
TI  - Attenuated influenza virus vaccines with modified NS1 proteins.
AB  - The development of reverse genetics techniques allowing the rescue of influenza
      virus from plasmid DNA has opened up the possibility of inserting mutations into
      the genome of this virus for the generation of novel live attenuated influenza
      virus vaccines. Modifications introduced into the viral NS1 gene via reverse
      genetics have resulted in attenuated influenza viruses with promising vaccine
      potential. One of the main functions of the NS1 protein of influenza virus is the
      inhibition of the innate host type I interferon-mediated antiviral response. Upon
      viral infection, influenza viruses with modified NS1 genes induce a robust local
      type I interferon response that limits their replication, resulting in disease
      attenuation in different animal models. Nevertheless, these viruses can be grown
      to high titers in cell- and egg-based substrates with deficiencies in the type I
      IFN system. Intranasal inoculation of mice, pigs, horses, and macaques with NS1
      modified influenza virus strains induced robust humoral and cellular immune
      responses, and generated immune protection against challenge with wild-type
      virus. This protective response was not limited to homologous strains of
      influenza viruses, as reduced replication of heterologous strains was also
      demonstrated in animals vaccinated with NS1-modified viruses, indicating the
      induction of a broad cross-neutralizing response by these vaccine candidates. The
      immunogenicity of NS1-modified viruses correlated with enhanced activation of
      antigen-presenting cells. While further studies on their safety and efficacy are
      still needed, the results obtained so far indicate that NS1-modified viruses
      could represent a new generation of improved influenza virus vaccines, and they
      suggest that modifying viral interferon antagonists in other virus families is a
      promising strategy for the generation of live attenuated virus vaccines.

PMID- 19768407
TI  - DNA vaccines against influenza viruses.
AB  - As an attractive alternative to conventional vaccines, DNA vaccines play a
      critical role in inducing protection against several infectious diseases. In this
      review, we discuss the advantages that DNA vaccines offer in comparison to
      conventional protein-based vaccines. We discuss strategies to improve the potency
      and efficacy of DNA vaccines. Specifically, we focus on the potential use of DNA
      based vaccines to elicit broad-spectrum humoral and cellular immunity against
      influenza virus. Finally, we discuss the advances made in the use of DNA vaccines
      to prevent avian H5N1 influenza.

PMID- 19768408
TI  - Recombinant proteins produced in insect cells.
AB  - Both purified expressed proteins and virus-like particles generated in insect
      cells by recombinant baculoviruses are being explored as potential vaccines for
      seasonal and pandemic influenza. Clinical trials have suggested that recombinant
      hemagglutinin vaccines are well tolerated in healthy and elderly adults, that
      they induce a functional antibody response, and that they provide protection
      against seasonal influenza in adults. In one trial, a pandemic formulation of H5
      vaccine (rH5) induced neutralizing antibody in adults at rates roughly similar to
      that seen with egg-derived subvirion H5N1 vaccine. Preliminary data suggest that
      vaccination with the rH5 can also prime for booster responses on revaccination
      with drifted strains of H5. Recombinant approaches may be extremely valuable in
      combating future pandemics and further studies of recombinant pandemic vaccines
      in humans are needed.

PMID- 19768409
TI  - Influenza neuraminidase as a vaccine antigen.
AB  - The neuraminidase protein of influenza viruses is a surface glycoprotein that
      shows enzymatic activity to remove sialic acid, the viral receptor, from both
      viral and host proteins. The removal of sialic acid from viral proteins plays a
      key role in the release of the virus from the cell by preventing the aggregation
      of the virus by the hemagglutinin protein binding to other viral proteins.
      Antibodies to the neuraminidase protein can be protective alone in animal
      challenge studies, but the neuraminidase antibodies appear to provide protection
      in a different manner than antibodies to the hemagglutinin protein. Neutralizing
      antibodies to the hemagglutinin protein can directly block virus entry, but
      protective antibodies to the neuraminidase protein are thought to primarily
      aggregate virus on the cell surface, effectively reducing the amount of virus
      released from infected cells. The neuraminidase protein can be divided into nine
      distinct antigenic subtypes, where there is little cross-protection of antibodies
      between subtypes. All nine subtypes of neuraminidase protein are commonly found
      in avian influenza viruses, but only selected subtypes are routinely found in
      mammalian influenza viruses; for example, only the N1 and N2 subtypes are
      commonly found in both humans and swine. Even within a subtype, the neuraminidase
      protein can have a high level of antigenic drift, and vaccination has to
      specifically be targeted to the circulating strain to give optimal protection.
      The levels of neuraminidase antibody also appear to be critical for protection,
      and there is concern that human influenza vaccines do not include enough
      neuraminidase protein to induce a strong protective antibody response. The
      neuraminidase protein has also become an important target for antiviral drugs
      that target sialic acid binding which blocks neuraminidase enzyme activity. Two
      different antiviral drugs are available and are widely used for the treatment of
      seasonal influenza in humans, but antiviral resistance appears to be a growing
      concern for this class of antivirals.

PMID- 19768410
TI  - Recombinant vectors as influenza vaccines.
AB  - The antiquated system used to manufacture the currently licensed inactivated
      influenza virus vaccines would not be adequate during an influenza virus
      pandemic. There is currently a search for vaccines that can be developed faster
      and provide superior, long-lasting immunity to influenza virus as well as other
      highly pathogenic viruses and bacteria. Recombinant vectors provide a safe and
      effective method to elicit a strong immune response to a foreign protein or
      epitope. This review explores the advantages and limitations of several different
      vectors that are currently being tested, and highlights some of the newer viruses
      being used as recombinant vectors.

PMID- 19768412
TI  - Pandemic influenza vaccines.
AB  - Since their compositions remain uncertain, universal pandemic vaccines are yet to
      be created. They would aim to protect globally against pandemic influenza viruses
      that have not yet evolved. Thus they differ from seasonal vaccines to influenza
      virus, which are updated annually in spring to incorporate the latest circulating
      viruses, and are then produced and delivered before the peak influenza season
      starts in late fall and winter. The efficacy of seasonal vaccines is linked to
      their ability to induce virus-neutralizing antibodies, which provide subtype
      specific protection against influenza A viruses. If pandemic vaccines were
      designed to resemble current vaccines in terms of composition and mode of action,
      they would have to be developed, tested, and mass-produced after the onset of a
      pandemic, once the causative virus had been identified. The logistic problems of
      generating a pandemic vaccine from scratch, conducting preclinical testing, and
      producing billions of doses within a few months for global distribution are
      enormous and may well be insurmountable. Alternatively, the scientific community
      could step up efforts to generate a universal vaccine against influenza A viruses
      that provides broadly cross-reactive protection through the induction of
      antibodies or T cells to conserved regions of the virus.

PMID- 19768411
TI  - Influenza virus-like particles as pandemic vaccines.
AB  - There is an urgent need to develop novel approaches for vaccination against
      emerging pathogenic avian influenza viruses as a priority for pandemic
      preparedness. Influenza virus-like particles (VLPs) have been suggested and
      developed as a new generation of non-egg-based cell culture-derived vaccine
      candidates against influenza infection. Influenza VLPs are formed by a self
      assembly process incorporating structural proteins into budding particles
      composed of the hemagglutinin (HA), neuraminidase (NA) and M1 proteins, and may
      include additional influenza proteins such as M2. Animals vaccinated with VLPs
      were protected from morbidity and mortality resulting from lethal influenza
      infections. The protective mechanism of influenza VLP vaccines was similar to
      that of the currently licensed influenza vaccines inducing neutralizing
      antibodies and hemagglutination inhibition activities. Current studies
      demonstrate that influenza VLP approaches can be a promising alternative approach
      to developing a vaccine for pandemic influenza viruses. The first human clinical
      trial of a recombinant pandemic-like H5N1 influenza VLP vaccine was initiated in
      July 2007 (Bright et al., unpublished).

PMID- 19768413
TI  - Adjuvants for pandemic influenza vaccines.
AB  - The use of adjuvants is being explored as a means of improving vaccine
      immunogenicity. This is particularly important for the development of vaccines
      against potential pandemic influenza virus strains. Adjuvants act by prolonging
      the exposure time of antigen to the immune system, enhancing the delivery of
      antigen to antigen-presenting cells, or providing immunostimulatory signals that
      potentiate the immune response. Aluminum salts are the only licensed adjuvant in
      the United States, but the combination of these salts with inactivated influenza
      A/H5N1 antigens has had little effect on seroresponses. Several oil-in-water
      adjuvants, including MF59 and AS03, have significantly enhanced immune responses
      in healthy adult vaccine recipients to inactivated influenza A/H5N1. Additional
      studies are needed in vulnerable populations (younger and elderly persons,
      pregnant women, and immunocompromised patients) to confirm the safety and
      enhanced immunogenicity of these promising formulations. A number of other
      adjuvants are under investigation to evaluate their ability to improve the
      immunogenicity of inactivated vaccines targeting influenza A/H5N1.

PMID- 19768414
TI  - Transcutaneous immunization with influenza vaccines.
AB  - Transcutaneous immunization (TCI) is a novel vaccination route involving the
      topical application of vaccine antigens on the skin. The skin is an attractive
      site for vaccination because it is rich in various antigen-capturing immune
      cells. The outer skin barrier can be overcome through the use of mild chemical
      and/or physical treatments, including ethanol-water hydration and stripping,
      which allows for large vaccine molecules or even particulate antigens to gain
      access to the skin's immune cells. The use of toxin adjuvants such as cholera or
      heat-labile toxins was demonstrated to enhance the immunogenicity of vaccine
      antigens, probably due to their stimulatory effects on immune cells. Oleic acid
      or retinoic acid, known as permeation enhancers or immune modulators, were found
      to increase immune responses to inactivated whole-influenza viral vaccines. The
      further development of more effective delivery systems and nontoxic adjuvants is
      needed to enhance the efficacy of this approach to vaccination.

PMID- 19768416
TI  - Animal models for evaluation of influenza vaccines.
AB  - Influenza viruses are emerging and re-emerging viruses that cause worldwide
      epidemics and pandemics. Despite substantial knowledge of the mechanisms of
      infection and immunity, only modest progress has been made in human influenza
      vaccine development. The rational basis for influenza vaccine development
      originates in animal models that have helped us to understand influenza species
      barriers, virus-host interactions, factors that affect transmission, disease
      pathogenesis, and disease intervention strategies. As influenza evolution can
      surmount species barriers and disease intervention strategies that include
      vaccines, our need for appropriate animal models and potentially new host species
      will evolve to meet these adaptive challenges. This chapter discusses animal
      models for evaluating vaccines and discusses the challenges and strengths of
      these models.

PMID- 19768415
TI  - Microneedle-based vaccines.
AB  - The threat of pandemic influenza and other public health needs motivate the
      development of better vaccine delivery systems. To address this need,
      microneedles have been developed as micron-scale needles fabricated using low
      cost manufacturing methods that administer vaccine into the skin using a simple
      device that may be suitable for self-administration. Delivery using solid or
      hollow microneedles can be accomplished by (1) piercing the skin and then
      applying a vaccine formulation or patch onto the permeabilized skin, (2) coating
      or encapsulating vaccine onto or within microneedles for rapid, or delayed,
      dissolution and release in the skin, and (3) injection into the skin using a
      modified syringe or pump. Extensive clinical experience with smallpox, TB, and
      other vaccines has shown that vaccine delivery into the skin using conventional
      intradermal injection is generally safe and effective and often elicits the same
      immune responses at lower doses compared to intramuscular injection. Animal
      experiments using microneedles have shown similar benefits. Microneedles have
      been used to deliver whole, inactivated virus; trivalent split antigen vaccines;
      and DNA plasmids encoding the influenza hemagglutinin to rodents, and strong
      antibody responses were elicited. In addition, ChimeriVax-JE against yellow fever
      was administered to nonhuman primates by microneedles and generated protective
      levels of neutralizing antibodies that were more than seven times greater than
      those obtained with subcutaneous delivery; DNA plasmids encoding hepatitis B
      surface antigen were administered to mice and antibody and T cell responses at
      least as strong as hypodermic injections were generated; recombinant protective
      antigen of Bacillus anthracis was administered to rabbits and provided complete
      protection from lethal aerosol anthrax spore challenge at a lower dose than
      intramuscular injection; and DNA plasmids encoding four vaccinia virus genes
      administered to mice in combination with electroporation generated neutralizing
      antibodies that apparently included both Th1 and Th2 responses. Dose sparing with
      microneedles was specifically studied in mice with the model vaccine ovalbumin.
      At low dose (1 microg), specific antibody titers from microneedles were one order
      of magnitude greater than subcutaneous injection and two orders of magnitude
      greater than intramuscular injection. At higher doses, antibody responses
      increased for all delivery methods. At the highest levels (20-80 microg), the
      route of administration had no significant effect on the immune response.
      Concerning safety, no infections or other serious adverse events have been
      observed in well over 1,000 microneedle insertions in human and animal subjects.
      Bleeding generally does not occur for short microneedles (<1 mm). Highly
      localized, mild, and transient erythema is often observed. Microneedle pain has
      been reported as nonexistent to mild, and always much less than a hypodermic
      needle control. Overall, these studies suggest that microneedles may provide a
      safe and effective method of delivering vaccines with the possible added
      attributes of requiring lower vaccine doses, permitting low-cost manufacturing,
      and enabling simple distribution and administration.

PMID- 19768417
TI  - Immunosenescence and influenza vaccine efficacy.
AB  - A number of protective immune functions decline with age along with physiological
      and anatomical changes, contributing to the increased susceptibility of older
      adults to infectious diseases and suboptimal protective immune responses to
      vaccination. Influenza vaccination is the most cost-effective strategy to prevent
      complications from influenza viral infections; however, the immunogenicity and
      effectiveness of currently licensed vaccines in the United States is about 30-50%
      in preventing complications arising from influenza and preventing death from all
      causes during winter months in older adults. Hence, it is crucial to understand
      the molecular mechanisms that lead to immune dysfunction as a function of age so
      that appropriate strategies can be developed to enhance the disease resistance
      and immunogenicity of preventive vaccines, including influenza vaccines, for the
      older adult population.

PMID- 19768418
TI  - Vaccines for pandemic influenza: summary of recent clinical trials.
AB  - The emergence of influenza A/H5N1 viruses in Asia has raised concerns about their
      potential to cause pandemic disease. Because vaccination is the primary strategy
      for the prevention of influenza, efforts are in progress to develop safe and
      immunogenic vaccines against these viruses and other potential pandemic influenza
      strains. Results of initial studies indicated that subunit influenza A/H5N1virus
      vaccines were poorly immunogenic, and that high dosages were needed to induce
      seroresponses in the majority of subjects. Addition of aluminum-containing
      adjuvants resulted in variable effects on the immunogenicity of H5 vaccines, but
      in general, clinically meaningful effects have not been observed. Intradermal
      immunization was not associated with significant enhancement in one study. More
      recent studies indicate that oil-in-water adjuvants significantly enhance immune
      responses when compared with nonadjuvanted preparations containing the same
      dosage of H5 or H9 hemagglutinin. In addition, these formulations elicit higher
      levels of cross-reactive antibodies vs. different H5N1 clades. Several whole
      virus vaccines have been demonstrated to stimulate high frequencies of responses
      at relatively low dosages; however, direct comparisons with subunit vaccines have
      not been made. Finally, candidate live attenuated vaccines are under evaluation
      in clinical trials. The results of these and future trials will help to identify
      formulations and immunization regimens for various populations, and will better
      prepare us to address the threat of both pandemic and interpandemic influenza.

PMID- 19768419
TI  - Considerations for licensure of influenza vaccines with pandemic and prepandemic
      indications.
AB  - With over 409 human cases of avian influenza and over 256 deaths worldwide
      resulting from infection with avian influenza (H5N1), an influenza pandemic is
      still a real threat, especially with H5N1 continuing to evolve into antigenically
      distinct clades. The Food and Drug Administration (FDA) along with other national
      regulatory authorities (NRAs) recognize the important role that safe and
      effective vaccines will play in protecting the public health from the threat of
      an influenza pandemic. The challenges to the FDA and other NRAs are significant
      as regulatory agencies pursue the development of new scientific and regulatory
      criteria to evaluate vaccines against pandemic influenza strains for licensure.
      To this end, the FDA is actively utilizing current regulatory processes such as
      accelerated approval and priority review as well as developing the regulatory
      pathways needed to speed the availability of vaccines against pandemic influenza.
      In May of 2007, the FDA issued two final guidance documents, one describing the
      clinical data recommended to support the licensure of annual influenza vaccines,
      and the other describing the clinical data recommended to support the licensure
      of pandemic influenza vaccines. These guidances contain specific approaches
      outlined by the FDA to assist manufacturers in developing new vaccines to
      increase the supply of safe and effective influenza vaccines for both annual and
      pandemic use. In this article we define the nomenclature "pandemic" and
      "prepandemic," describe the regulatory pathway for licensing new influenza
      vaccines for pandemic and prepandemic use, and outline considerations for
      evaluating pandemic/prepandemic vaccines that have been formulated using new
      approaches such as cell culture and non-aluminum salt adjuvants.

PMID- 19768420
TI  - Strategies for broad global access to pandemic influenza vaccines.
AB  - The global need for a pandemic influenza vaccine is large. High-income countries
      have stated their intent to provide universal access for pandemic influenza
      vaccine to their populations. Assuming that a two-dose schedule would be needed,
      providing universal coverage globally would represent approximately 6.5 billion
      two-dose courses or 13 billion doses. In the best case scenario, should an
      outbreak of pandemic influenza occur in the near term, using H5N1 as a proxy for
      the pandemic virus, the total available doses for the global population within
      six months of an out break would be only 1.2 billion courses or 2.4 billion
      doses. In addition, current stockpiles of pandemic influenza vaccine are limited.
      However, promising developments are occurring with respect to global capacity,
      technological innovation, and global conviction that offer potential solutions to
      the problem of pandemic influenza vaccine supply for the world's population.

PMID- 19768421
TI  - Prioritization of pandemic influenza vaccine: rationale and strategy for decision
      making.
AB  - Few catastrophes can compare with the global impact of a severe influenza
      pandemic. The 1918-1919 pandemic was associated with more than 500,000 deaths in
      the USA and an estimated 20-40 million deaths worldwide, though some place the
      global total much higher. In an era when infectious disease mortality had been
      steadily decreasing, the 1918-1919 pandemic caused a large spike in overall
      population mortality, temporarily reversing decades of progress. The US
      Department of Health and Human Services, extrapolating from the 1918-1919
      pandemic to the current US population size and demographics, has estimated that a
      comparable pandemic today would result in almost two million deaths. Vaccination
      is an important component of a pandemic response. Public health measures such as
      reduction of close contacts with others, improved hygiene, and respiratory
      protection with facemasks or respirators can reduce the risk of exposure and
      illness (Germann et al. 2006; Ferguson et al. 2006), but would not reduce
      susceptibility among the population. Prophylaxis with antiviral medications also
      may prevent illness but depends on the availability of large antiviral drug
      stockpiles and also does not provide long-term immunity. By contrast,
      immunization with a well-matched pandemic vaccine would provide active immunity
      and represent the most durable pandemic response. However, given current
      timelines for the development of a pandemic influenza vaccine and its production
      capacity, vaccine is likely not to be available in sufficient quantities to
      protect the entire population before pandemic outbreaks occur, and thus
      potentially limited stocks may need to be prioritized. This chapter reviews
      information on influenza vaccine production capacity, describes approaches used
      in the USA to set priorities for vaccination in the setting of limited supply,
      and presents a proposed strategy for prioritization.

PMID- 19768422
TI  - High resolution multimode light microscopy of cell migration: long-term imaging
      and analysis.
AB  - Cell migration is a multi-step process that involves sequential changes in the
      cytoskeleton, cell-substrate adhesion and components of the extracellular matrix.
      In multicellular organisms, directional cell migration is important for normal
      development, wound healing and immune responses and contributes to disease states
      such as tumor formation and metastasis. Many cells such as fibroblasts migrate as
      individuals while others, such as keratinocytes, move as groups or sheets of
      cells.In this chapter, we use human oral keratinocytes (OKF6/TERT-2) to
      illustrate the complex patterns of cell migration and its regulation. In culture,
      sheets of keratinocytes migrate and respond to human pathogens such as Candida
      albicans. The dynamic changes of the cytoskeleton, cell-cell and cell-substrate
      interactions that change during an infection for example require observation over
      long periods of time in order to identify the spatio-temporal coordinated
      regulation of the cytoskeleton and its associated components as well as the
      signaling pathways that control them.Microscopic techniques for long-term live
      cell observation and analysis of cell migration require high-resolution imaging
      systems that maintain perfect focus and optimal growth conditions (temperature,
      CO(2)) for cells. We describe two multimode digital imaging systems (VEC-DIC and
      BioStation IM), both with wide-field epifluorescence and transmitted light
      objectives for long-term time-lapse imaging and motion analysis.

PMID- 19768423
TI  - Imaging the cytoskeleton in live Xenopus laevis embryos.
AB  - Historically, much of our understanding of actin filaments, microtubules and
      intermediate filaments has come from the study of fixed cells and tissues. But
      the cytoskeleton is inherently dynamic, and so developing the means to image it
      in living cells has proved crucial. Advances in confocal microscopy and
      fluorescent protein technologies have allowed us to dynamically image the
      cytoskeleton at high resolution and so learn much more about its cellular
      functions. However, most of this work has been performed in cultured cells, and a
      critical next step is to understand how the cytoskeleton functions in the context
      of an intact organism. We, and others, have developed methods to image the
      cytoskeleton in living vertebrate embryos. Here, we describe an approach to image
      the cytoskeleton in embryos of the frog, Xenopus laevis, using mRNA to express
      fluorescently tagged cytoskeletal probes and confocal microscopy to visualize
      their dynamic behavior.

PMID- 19768424
TI  - Live-cell imaging of the cytoskeleton and mitochondrial-cytoskeletal interactions
      in budding yeast.
AB  - This chapter describes labeling methods and optical approaches for live-cell
      imaging of the cytoskeleton and of a specific organelle-cytoskeleton interaction
      in budding yeast.

PMID- 19768425
TI  - Jasplakinolide: an actin-specific reagent that promotes actin polymerization.
AB  - Jasplakinolide, a cyclo-depsipeptide is a commonly used actin filament
      polymerizing and stabilizing drug. The substance has originally been isolated
      from a marine sponge, and can now be synthesized and has become commercially
      available. This, together with the benefit that jasplakinolide is membrane
      permeable has made it a commonly used tool in cell biology, when actin filament
      stabilization or polymerization has to be achieved. This may either be the case
      in studies on morphogenesis, motility, organelle movement, or when apoptosis has
      to be induced. Its use as a potent anticancer drug is discussed. The direct
      action on actin filaments may have further consequences in golgi body and
      membrane raft protein organization. In this chapter, the visualization of
      jasplaklinolide effects by different fluorescent and transmission electron
      microscopic methods is described. As competitive binding capacities of
      jasplakinolide and phalloidin make the detection of actin filaments by
      fluorescently labeled phalloidin problematic, alternatives are given here.

PMID- 19768426
TI  - Analysis of centrosome function and microtubule dynamics by time-lapse microscopy
      in Xenopus egg extracts.
AB  - Centrosomes are essential organelles that organize the microtubule cytoskeleton
      during interphase and mitosis. Centrosomes are assembled from tens to hundreds of
      proteins, but how these proteins are organized into functional microtubule
      nucleating and organizing centers is not yet clear. An important step in
      understanding the role of individual proteins in centrosome function is to
      understand whether they are involved in forming, stabilizing, or anchoring
      microtubules. It is becoming increasingly clear that the analysis of fixed
      samples is inadequate for a true understanding of the dynamics that drive cell
      biological processes. In this chapter we focus on methods to analyze microtubule
      nucleation, organization, and dynamics using assays based on mitotic Xenopus egg
      extracts and in vitro reactions. These methods can easily be adapted to the study
      of interphase processes, or to the study of other cytoskeletal proteins and their
      dynamics.

PMID- 19768427
TI  - Quantitative fluorescence microscopy techniques.
AB  - Fluorescence microscopy is a non-invasive technique that allows high resolution
      imaging of cytoskeletal structures. Advances in the field of fluorescent
      labelling (e.g., fluorescent proteins, quantum dots, tetracystein domains) and
      optics (e.g., super-resolution techniques and quantitative methods) not only
      provide better images of the cytoskeleton, but also offer an opportunity to
      quantify the complex of molecular events that populate this highly organised, yet
      dynamic, structure.For instance, fluorescence lifetime imaging microscopy and
      Forster resonance energy transfer imaging allow mapping of protein-protein
      interactions; furthermore, techniques based on the measurement of photobleaching
      kinetics (e.g., fluorescence recovery after photobleaching, fluorescence loss in
      photobleaching, and fluorescence localisation after photobleaching) permit the
      characterisation of axonal transport and, more generally, diffusion of relevant
      biomolecules.Quantitative fluorescence microscopy techniques offer powerful tools
      for understanding the physiological and pathological roles of molecular
      machineries in the living cell.

PMID- 19768428
TI  - A FRET-based approach for studying conformational changes of a cytoskeleton
      related tumor suppressor molecule.
AB  - Changes in conformation are an important regulatory mechanism for a wide variety
      of proteins. Proteins whose activity must change in response to external stimuli
      often undergo dramatic changes in their tertiary structure in a temporally and
      spatially coordinated manner, resulting in a change in enzymatic activity or in
      the profile of binding partners. To understand how these proteins function, it is
      critically important to be able to monitor the timing and subcellular
      localization of these conformational changes, preferably in a quantitative manner
      and in the context of a living cell. Unfortunately, there is a dearth of
      experimental techniques that can detect changes in conformation directly. In this
      chapter, we describe an approach that takes advantage of fluorescence resonance
      energy transfer (FRET), a well-known physical phenomenon between a spectrally
      compatible pair of fluorescent molecules, which is exquisitely sensitive to the
      distance between them. Combined with the use of proteins of the green fluorescent
      protein (GFP) family, this approach can be used to detect changes in protein
      conformation in vitro and in vivo effectively.

PMID- 19768429
TI  - Sample preparation for fluorescence imaging of the cytoskeleton in fixed and
      living plant roots.
AB  - During the past decade the use of live cytoskeletal probes has increased
      dramatically due to the introduction of the green fluorescent protein. However,
      to make full use of these live cell reporters it is necessary to implement simple
      methods to maintain plant specimens in optimal growing conditions during imaging.
      To image the cytoskeleton in living Arabidopsis root cells, we rely on a system
      involving coverslips coated with nutrient supplemented agar where the seeds are
      directly germinated. This coverslip system can be conveniently transferred to the
      stage of a confocal microscope with minimal disturbance to the growth of the
      seedling. Parallel to our live cell imaging approaches, we routinely process
      fixed plant material via indirect immunofluorescence. For these methods we
      typically use nonembedded vibratome-sectioned and whole mount permeabilized root
      tissue. The clearly defined developmental regions of the root provide us with an
      elegant system to further understand the cytoskeletal basis of plant development.

PMID- 19768430
TI  - Imaging of the cytoskeleton and mitochondria in fixed budding yeast cells.
AB  - The budding yeast Saccharomyces cerevisiae has many advantages as a model system,
      but until recently, high-resolution microscopy was not often attempted in this
      organism. Its small size, rounded shape, and rigid cell wall were obstacles to
      exploring the cell biology of this model eukaryote. However, it is now feasible
      for laboratories to acquire and analyze high-resolution multidimensional images
      of yeast cell biology. As a result, imaging of yeast has emerged as an important
      tool in eukaryotic cell biology. This chapter describes labeling methods and
      optical approaches for visualizing the cytoskeleton and interactions of the actin
      cytoskeleton with mitochondria in fixed yeast cells using fluorescence
      microscopy.

PMID- 19768431
TI  - Imaging cytoskeleton components by electron microscopy.
AB  - The cytoskeleton is a complex of detergent-insoluble components of the cytoplasm
      playing critical roles in cell motility, shape generation, and mechanical
      properties of a cell. Fibrillar polymers-actin filaments, microtubules, and
      intermediate filaments- are major constituents of the cytoskeleton, which
      constantly change their organization during cellular activities. The actin
      cytoskeleton is especially polymorphic, as actin filaments can form multiple
      higher order assemblies performing different functions. Structural information
      about cytoskeleton organization is critical for understanding its functions and
      mechanisms underlying various forms of cellular activity. Because of the
      nanometer-scale thickness of cytoskeletal fibers, electron microscopy (EM) is a
      key tool to determine the structure of the cytoskeleton.This article describes
      application of rotary shadowing (or metal replica) EM for visualization of the
      cytoskeleton. The procedure is applicable to thin cultured cells growing on glass
      coverslips and consists of detergent extraction of cells to expose their
      cytoskeleton, chemical fixation to provide stability, ethanol dehydration and
      critical point drying to preserve three-dimensionality, rotary shadowing with
      platinum to create contrast, and carbon coating to stabilize replicas. This
      technique provides easily interpretable three-dimensional images, in which
      individual cytoskeletal fibers are clearly resolved, and individual proteins can
      be identified by immunogold labeling. More importantly, replica EM is easily
      compatible with live cell imaging, so that one can correlate the dynamics of a
      cell or its components, e.g., expressed fluorescent proteins, with high
      resolution structural organization of the cytoskeleton in the same cell.

PMID- 19768432
TI  - Purification and localization of intraflagellar transport particles and
      polypeptides.
AB  - The growth and maintenance of almost all cilia and flagella are dependent on the
      proper functioning of the process of intraflagellar transport (IFT). This
      includes the primary cilia of most cells in humans that are in interphase or the
      G(o) phase of the cell cycle. The model system for the study of IFT is the
      flagella of the bi-flagellate green alga Chlamydomonas. It is in this organism
      that IFT was first discovered, and genetic data from a Chlamydomonas mutant first
      linked the process of IFT to polycystic kidney disease in humans. The information
      given in this chapter addresses procedures to purify IFT particles from flagella
      and localize these particles, and their associated motor proteins, in flagella
      using light and electron microscopic approaches.

PMID- 19768433
TI  - High pressure freezing, electron microscopy, and immuno-electron microscopy of
      Tetrahymena thermophila basal bodies.
AB  - Preservation of Tetrahymena thermophila basal body ultrastructure for
      visualization by transmission electron microscopy is improved by a combination of
      high pressure freezing (HPF) and freeze substitution (FS). These methods also
      reliably retain the antigenicity of cellular proteins for immuno-electron
      microscopy, which enables the precise localization of green fluorescent protein
      (GFP)-tagged and native basal body proteins. The plastic-embedded samples
      generated by these methods take full advantage of higher resolution visualization
      techniques such as electron tomography. We describe protocols for cryofixation,
      FS, immunolabeling, and staining. Suggestions for trouble shooting and evaluation
      of specimen quality are discussed. In combination with identification and
      manipulation of a rapidly expanding list of basal body-associated gene products,
      these methods are being used to increase our understanding of basal body
      composition, assembly, and function.

PMID- 19768434
TI  - Strategies for imaging microtubules in plant cells.
AB  - Microtubules are required throughout plant development for a wide variety of
      processes, and different strategies have been evolved to visualize them. This
      chapter summarizes the most effective of these methods and points out potential
      problems and pitfalls. We outline the freeze-shattering method for immunolabeling
      microtubules in aerial organs such as leaves that require mechanical
      permeabilization, discuss current options for live cell imaging of MTs with
      fluorescently tagged proteins (FPs), and provide different fixation protocols for
      preserving MTs for transmission electron microscopy including chemical fixation,
      high pressure freezing/freeze substitution, and post-fixation staining procedures
      for transmission electron microscopy.

PMID- 19768435
TI  - A rapid tracking method for the quantitative analysis of organelle streaming
      velocity.
AB  - A key to understanding cytoskeletal mechanisms of eukaryotic cells is found in
      their internal motility. In many plant cell types, these motile events, termed
      "cytoplasmic streaming", are very impressive with rapid movement of organelles
      over long distances. Like many other features of cytoplasmic streaming, organelle
      velocity is determined by acto-myosin-related mechanisms. Therefore, the
      quantification of streaming velocity aids the characterization of important
      factors contributing to cytoskeleton function. Usually, the movement velocity
      varies greatly between particles and exhibits rapid changes. This complexity
      makes measurements very cumbersome and requires large cell numbers and a lot of
      imaging data for statistical evaluation. Focusing on a triplet of rapidly moving
      organelles in a single cell proved to be an efficient method for determining
      organelle displacement in a direct, standardized manner. This approach requires
      only a few cells and allows the evaluation of potential factors involved in
      cytoplasmic streaming with a relatively low temporal and technical effort. This
      chapter evaluates two examples that show the high sensitivity of the method in
      the detection of differences in organelle streaming velocities. These include the
      retardation of streaming upon myosin inhibition and a similar, but much less
      expected, response following the overexpression of actin-binding proteins.

PMID- 19768436
TI  - Melanosome motility in fish retinal pigment epithelial cells.
AB  - Several model systems have been developed to investigate intracellular organelle
      motility. A relatively novel system that is simple but useful for studying
      mechanisms of organelle motility is the fish retinal pigment epithelial (RPE)
      cell. Primary cultures of dissociated RPE cells are easily prepared and amenable
      to organelle motility studies. In vivo, melanin-containing pigment granules
      (melanosomes) within the RPE migrate long distances in response to light flux.
      When cultured in vitro, RPE cells attach to the substrate with the apical
      projections extending radially from the central cell body. Melanosomes can be
      chemically triggered to aggregate or disperse throughout the projections, and can
      be easily observed using phase contrast microscopy. Melanosome migration in RPE
      apical projections is dependent on actin filaments, and thus renders this model
      system useful for investigations of actin-dependent organelle motility.

PMID- 19768437
TI  - Analysis of properties of cilia using Tetrahymena thermophila.
AB  - Cilia and eukaryotic flagella are important structures required for the motility
      of cells, the movement of medium across the surfaces of cells, and the
      connections between the receptor and synthetic portions of sensory cells. The
      axoneme forms the cytoskeleton of the cilium comprising several hundreds of
      proteins that assemble into the 9 + 2 arrangement of outer doublet and central
      pair microtubules, the inner and outer rows of dynein arms, and many other
      structures. Tetrahymena thermophila is an excellent model organism for the study
      of cilia and ciliogenesis. The cell is covered by about 1,000 cilia which are
      essential for survival. Additionally, the Tetrahymena genome is available and
      targeted genetic manipulations are straightforward. In this chapter, we describe
      five protocols that examine properties of cilia: (a) measuring mRNA levels to see
      the effect of deciliation on gene expression; (b) swimming velocity and
      linearity; (c) ciliary length and density; (d) phagocytosis that occurs through
      the ciliated oral apparatus; and (e) depolarization-induced ciliary reversal.

PMID- 19768438
TI  - Application of cell traction force microscopy for cell biology research.
AB  - When a cell migrates, it generates traction forces on the underlying substrate.
      The cell traction force (CTF) is not only essential for cell migration, but it is
      also used by cells to control their shape and maintain cellular homeostasis. As
      such, quantification of CTFs aids in better understanding of many fundamental
      biological processes such as morphogenesis, angiogenesis, and wound healing of
      tissues and organs. A new technology called cell traction force microscopy (CTFM)
      has been developed to determine CTFs in a quantitative fashion. The advantage of
      this technology is that it directly measures the "cause" (i.e., CTFs) of cell
      movement instead of the "effect" (i.e., cell movement itself), which is measured
      by various conventional methods. This chapter provides detailed information of
      materials and methods that are needed in order to perform typical CTFM
      experiments. Several examples are also given to illustrate various applications
      of CTFM in cell biology research.

PMID- 19768439
TI  - 2D and 3D quantitative analysis of cell motility and cytoskeletal dynamics.
AB  - 2D- and 3D-Dynamic Image Analysis Systems (2D- and 3D-DIAS) for quantitative
      analysis of cell motility and chemotaxis are described. Particular attention is
      given to protocols that have proven useful in the quantitation of cell shape
      changes and pseudopod dynamics during basic cell motility (i.e. crawling in the
      absence of a chemotactic or other type of extracellular signal) and directed
      motion. In addition, methods provided, highlight the applicability of this
      approach to the accurate phenotypic characterizations of cytoskeletal mutations
      in Dictyostelium discoideum, cytoskeletal alterations in metastatic cells, and
      cytoskeletal defects in chemotactically defective polymorphonuclear neutrophils.

PMID- 19768440
TI  - Detergent-extracted models for the study of cilia or flagella.
AB  - Methods for using non-ionic detergents to produce demembranated and reactivated
      cilia and flagella are described in detail. Demembranated and reactivated cell
      models are useful as a research tool for studying motility function in flagella
      and cilia. When the plasma membrane is removed, the factors regulating motility
      can be studied under standardized experimental conditions that otherwise would be
      impossible. Practical insight is provided to understand the important factors in
      producing stable reactivated models. In addition, several useful variations of
      the method are presented for different types of mammalian and non-mammalian
      flagellar and ciliary systems.

PMID- 19768441
TI  - The analysis of intermediate filament dynamics using transfections and cell
      fusions.
AB  - The intermediate filament (IF) proteins have been recently found as dynamic
      structures that influence several aspects of cell homeostasis. Here, two
      alternative approaches to study the dynamics of IF proteins are described: the
      formation of cell hybrids by the fusion of different parental cells, and the
      transfection of keratin genes in cultured cells. In the first case, the selection
      of parental cell lines and the use of specific antibodies allow us to study how
      IF proteins recombine and copolymerize to form the heterokaryon cytoskeleton by
      immunofluorescence. In the second approach, some modifications of conventional
      transfection protocols allow the synchronized expression conditions, making it
      suitable for the analysis of the incorporation of a newly synthesized IF protein
      into the preexisting IF cytoskeleton of transfected cells.

PMID- 19768442
TI  - Functional analysis of actin-binding proteins in the central nervous system of
      Drosophila.
AB  - Using Drosophila actin-binding protein Dunc-115 as an example, this chapter
      describes an MARCM based method for analyzing cytoskeletal components for their
      functions in the nervous system. Following a concise description about the
      principle, a step-by-step protocol is provided for generating the needed stocks
      and for histological analysis. Additional details and explanations have been
      given in the accompanying notes. With the two together, it should provide a
      practical and comprehensive recipe for performing at the single cell level loss
      of-function and gain-of-function analyses of proteins associated with the
      cytoskeleton.

PMID- 19768443
TI  - Proteomic tools for the analysis of cytoskeleton proteins.
AB  - Proteomic tools have become an essential part of the tool kit of the molecular
      biologist, and provide techniques for detecting homologous sequences, recognizing
      functional domains, modeling, and analyzing the three-dimensional structure for
      any given protein sequence. Although a wealth of structural and functional
      information is available for a large number of members of the various classes of
      cytoskeletal proteins, many more members remain uncharacterized. These
      computational tools that are freely and easily accessible to the scientific
      community provide an excellent starting point to predict the structural and
      functional properties of such partially or fully uncharacterized protein
      sequences, and can lead to elegantly designed experiments to probe the
      hypothesized function. This chapter discusses various proteomic analysis tools
      with a focus on protein structure and function predictions.

PMID- 19768444
TI  - [Bilateral spontaneous carotid artery dissection in osteogenesis imperfecta (type
      I)].
AB  - We report on a 36-year-old patient with an acute cerebral infarction due to a
      spontaneous dissection of both internal carotid arteries in conjunction with type
      I osteogenesis imperfecta. Spontaneous dissections of cerebral arteries (DCA)
      represent a common cause of cerebral infarctions in younger patients. Our case
      shows that a hereditary connective tissue disorder should be considered in all
      patients with "spontaneous" DCA. The identification of an - initially unknown -
      hereditary connective tissue disorder may con-tribute to primary and secondary
      prophylaxis of cerebral ischemia.

PMID- 19768445
TI  - [Gottfried Benn and schizoidism].
AB  - Based on increasing criticism concerning operational diagnostics in psychiatry,
      the concept of schizoid personality disorder in ICD and DSM is discussed
      critically. In a case study regarding the poet and doctor Gottfried Benn, the
      limitation of manualized, context-independent diagnostic systems is shown. In
      contrast Ernst Kretschmer's concept of schizoidism seems suitable to describe a
      schizoid character in his ambiguity.

PMID- 19768447
TI  - [Attention deficit hyperactivity syndrome throughout the life span].
AB  - Attention deficit hyperactivity disorder (ADHD) is one of the most common
      neuropsychiatric disorders in children. ADHD is often chronic persisting into
      adulthood in about 60% of patients. The disorder is frequently associated with co
      occurring disruptive, anxiety, mood and personality disorders as well as
      substance abuse. The diagnosis of ADHD has to be based on careful assessment of
      symptoms and impairments in the different phases of life. Recent neuroimaging and
      genetic data support the neurobiological basis of the disorder. Multimodal
      treatment options including stimulants, antidepressants and behavioral therapy
      play a fundamental role in the management of ADHD across the life span.

PMID- 19768448
TI  - [Personality disorders in childhood and adolescence].
AB  - The diagnosis of a personality disorder is defined by the fact that personality
      traits are formed by early childhood, but German clinicians very rarely diagnose
      children and adolescents with personality disorders. Opponents of diagnosing
      personality disorders in childhood want to avoid labeling and refer to the
      developmental aspect of the personality. Supporters argue that children and
      adolescents already possess a describable personality and the developmental
      process continues into adulthood. By recognizing the pathological personality
      tendencies early enough allows an early therapy which can prevent an acute
      progression. The aim of the present study was to ascertain whether the Structured
      Clinical Interview for DSM-IV Personality Disorders (SCID-II) is applicable for
      use with adolescents. This empirical study indicated that one-third of the
      adolescents investigated were still diagnosed with a personality disorder 1 year
      after the primary assessment. However, the present categorizing diagnosis system
      proved to be insensible for childhood and adolescence. This supports the notion
      that dimensional systems are needed to diagnose personality traits in childhood
      in adolescence.

PMID- 19768449
TI  - [Postoperative pain therapy after radical prostatectomy    with and without
      epidural analgesia].
AB  - Epidural analgesia for postoperative pain treatment is favored, for example,
      within the scope of so-called fast-track surgery, especially abdominal surgery.
      To improve pain care for our urological patients, we examined the quality of
      postoperative pain therapy with and without epidural analgesia after radical
      prostatectomy. After the investigation was approved by the local ethics
      committee, patients were questioned in detail about the pain they experienced for
      7 days after radical prostatectomy. For all 7 postoperative observation days,
      significantly less pain was measured for patients receiving epidural analgesia
      compared with patients without epidural analgesia. This could be shown for the
      average and strongest pain intensity at rest as well as for pain during
      mobilization. Patients with epidural analgesia were discharged, on average, 1 day
      earlier. After radical prostatectomy, postoperative pain therapy with epidural
      analgesia seems to offer advantages with regard to the quality of analgesia and
      the average length of hospital stay.

PMID- 19768450
TI  - [Cementless humeral surface replacement arthroplasty in patients less than 55
      years of age].
AB  - BACKGROUND: Cementless humeral surface replacement arthroplasty is a viable
      treatment option for degenerative diseases of the shoulder joint. The aim of this
      prospective study was to analyse the results of this treatment option in patients
      younger than 55 years of age with different pathologies of the shoulder. PATIENTS
      AND METHODS: Twenty-three patients (26 implants) treated with cementless humeral
      surface replacement arthroplasty were included in this study. Mean follow-up was
      2.5 years (1-6 years). Ten patients had posttraumatic osteoarthritis, seven had
      primary osteoarthritis, and six had osteonecrosis. Patients were evaluated using
      the Constant score, shoulder motion, and subjective satisfaction. RESULTS: The
      mean Constant score increased significantly from 33 points preoperatively (8-69
      points) to 61 points postoperatively (25-83 points; p<0.0001), adjusted to age
      and gender from 38% (8-86%) to 70% (28-114%; p<0.0001). Significant improvement
      for the whole cohort was found regarding patients' pain, activity, mobility,
      shoulder flexion and abduction, and internal and external rotation (p<0.001). In
      one case, reoperation was necessary due to a superficial wound infection, and in
      another case, implant revision to a total shoulder replacement was performed
      because of glenoid erosion. CONCLUSION: Cementless humeral surface replacement
      arthroplasty is a viable bone-preserving treatment option for young and active
      patients. Later conversion to total shoulder replacement is possible. Good
      clinical results, a low complication rate, and high patient satisfaction were
      found in the short and mid term. Long-term investigations are necessary to
      confirm these observations.

PMID- 19768451
TI  - [From natural growth to artificial composition: the use of artificial materials
      in endoprosthetics from a cultural-historical perspective].
AB  - The use of artifical materials in joint replacement is not self-evident. A
      paradigm change can be observed. Beginning in the 18th century orthopedic surgery
      became possible because of a change of the idea of man. Natural growth was seen
      as ideal solution in orthopedic surgery until the 19th century. Yet in the
      aftermath the point of view changed to a more technical determined approach.
      Until the middle of the 20th century the terms "efficieny" and "ability" became
      more and more important. Joint replacement with artificial materials was
      generally accepted and led to an enormous accelaration in the development of new
      materials and surgical techniques.

PMID- 19768452
TI  - Critical care management of lung cancer patients to prolong life without
      prolonging dying.

PMID- 19768453
TI  - Six-month prognosis of patients with lung cancer admitted to the intensive care
      unit.
AB  - BACKGROUND: Intensive care unit (ICU) admission of patients with lung cancer
      remains debated because of the poor short-term prognosis. However, ICU admission
      of such patients should also be assessed on the possibility to administer
      specific anticancer treatment and the long-term outcome thereafter. OBJECTIVES:
      To identify predictive factors of hospital and 6-month mortality in critically
      ill lung-cancer patients. DESIGN AND SETTING: Retrospective study conducted in
      the ICU of a university hospital. PATIENTS: One hundred five consecutive lung
      cancer patients included between 1 January 1997 and 31 December 2006.
      INTERVENTIONS: None. RESULTS: Of the 105 patients (mean age 64.8 years), 87 (83%)
      had a non-small cell lung cancer (NSCLC). Extensive disease was diagnosed in 85
      patients (83%) (NSCLC stages IIIB and IV or disseminated small cell lung cancer).
      The main reasons for ICU admission were acute respiratory failure (59%) and/or
      hemoptysis (45%). Forty-three patients (41%) needed mechanical ventilation (MV).
      The ICU, hospital and 6-month mortality rates were 43, 54 and 73%, respectively.
      A performance status (PS) >or=2 [odds ratio OR = 3.6 (95% confidence interval CI
      (1.5-8.7)] and acute respiratory failure [OR = 3.5 (95% CI (1.5-8.4)] predicted
      hospital mortality. In a multivariate Cox model, the cancer progression [hazard
      ratio HR = 6.1 (95% CI 2.2-17)] and the need for MV [HR = 3.6 (95% CI 1.35-9.4)]
      were independently associated with 6-month mortality. Two-thirds of the ICU
      survivors were able to receive anticancer treatment. CONCLUSIONS: ICU admission
      should be considered in selected patients with lung cancer (PS <2, no cancer
      disease progression).

PMID- 19768454
TI  - Intra-articular morphine and bupivicaine for post-operative analgesia in anterior
      cruciate ligament reconstruction: a prospective randomised controlled trial.
AB  - Anterior cruciate ligament reconstruction (ACLR) has the potential for
      significant post-operative pain. Conventional systemic opiate treatment may cause
      nausea and drowsiness, which may delay recovery. The use of intra-articular local
      anaesthesia has been shown to be effective. We wished to examine the additional
      effect of intra-articular morphine. This is a prospective, randomised, double
      blind trial. Sixty patients were randomised to receive 20 ml 0.5% bupivicaine
      (group L, n = 30) or bupivicaine with 10 mg morphine (group M, n = 30) by intra
      articular injection at the end of the operation. Visual analogue scores (VAS)
      were recorded before ACLR (expected pain) and repeated at 6 and 24 h after
      surgery. Time to first analgesic request and total systemic opiate and other
      analgesic use in the first 24 h was recorded. Pre-operative VAS measurements did
      not predict pain or analgesic use post-operatively. There were no significant
      differences between groups L and M with regard post-operative VAS or time to
      first analgesic request. Group M required less opiate analgesic post-operatively
      (oral morphine equivalent 50 mg for group L and 27 mg for group M, P < 0.007).
      There were no complications associated with the intra-articular analgesic. The
      simple addition of morphine to the intra-articular injection of bupivicaine gives
      a significant reduction in opiate analgesic requirement after ACLR.

PMID- 19768456
TI  - Proteins, membranes and cells: the structure-function  nexus-ASB 2008.

PMID- 19768455
TI  - Inhibitory effects of cigarette smoke extract on neural crest migration occur
      through suppression of R-spondin1 expression via aryl hydrocarbon receptor.
AB  - Although it is known that smoking during pregnancy induces fetal malformations,
      few basic studies at the molecular level are currently available. Since it is
      known that neural crest cells (NCC) play an important role in tissue development
      and differentiation, we investigated the influence of cigarette smoke extract
      (CSE) on NCC migration. CSE treatment reduced the migration index of NCC in dose-
      and tar-content-dependent manners without induction of apoptosis or decrease in
      proliferation of NCC. alpha-Naphthoflavone, an antagonist of aryl hydrocarbon
      receptor (AhR), prevented the reduction in NCC migration that was otherwise
      induced by CSE treatment. Overexpression of AhR caused a significant decrease in
      NCC migration index, implying that CSE can attenuate NCC migration through AhR
      signaling. Transcriptome analysis revealed that overexpression of AhR led to
      decreased expression of R-spondin1 in NCC. Furthermore, overexpression of R
      spondin1 prevented the inhibitory effect of CSE on NCC. These results suggest
      that CSE causes suppressed expression of R-spondin1 by activating signals via the
      AhR, which leads to impaired neural crest cell migration.

PMID- 19768457
TI  - Pyranose dehydrogenases: biochemical features and perspectives of technological
      applications.
AB  - Pyranose dehydrogenase is a fungal flavin-dependent sugar oxidoreductase which is
      structurally and catalytically related to fungal pyranose oxidase and cellobiose
      dehydrogenase and probably fulfills similar biological functions in
      lignocellulose breakdown. It is a monomeric secretory glycoprotein and is limited
      to a rather small group of litter-decomposing basidiomycetes. Compared with
      pyranose oxidase, it displays broader substrate specificity and a variable
      regioselectivity and is unable to utilize oxygen as electron acceptor using
      substituted benzoquinones and (organo) metallic ions instead. Depending on the
      structure of the sugar in pyranose form (mono/di/oligosaccharide or glycoside)
      and the enzyme source, selective monooxidations at C-1, C-2, C-3, or dioxidations
      at C-2,3 or C-3,4 of the molecule to the corresponding aldonolactones (C-1), or
      (di)dehydrosugars (aldos(di)uloses) can be performed. These features make
      pyranose dehydrogenase a promising and versatile biocatalyst for production of
      highly reactive, sometimes unique, di- and tri-carbonyl sugar derivatives that
      may serve as interesting chiral intermediates for the synthesis of rare sugars,
      novel drugs, and fine chemicals.

PMID- 19768458
TI  - A B-cell lymphoma vaccine using a depot formulation of interleukin-2 induces
      potent antitumor immunity despite increased numbers of intratumoral regulatory T
      cells.
AB  - Therapeutic vaccination holds great potential as complementary treatment for non
      Hodgkin's lymphoma. Here, we report that a therapeutic whole cell vaccine
      formulated with IL-2 adsorbed onto aluminum hydroxide as cytokine-depot
      formulation elicits potent antitumor immunity and induces delayed tumor growth,
      control of tumor dissemination and longer survival in mice challenged with A20
      lymphoma. Therapeutic vaccination induced higher numbers of tumor's infiltrating
      lymphocytes (CD4(+) and CD8(+) T cells and NK cells), and the production of IFN
      gamma and IL-4 by intratumoral CD4(+) T cells. Further, strong tumor antigen
      specific cellular responses were detected at systemic level. Both the A20-derived
      antigenic material and the IL-2 depot formulation were required for induction of
      an effective immune response that impacted on cancer progression. All mice
      receiving any form of IL-2, either as part of the vaccine or alone as control,
      showed higher numbers of CD4(+)CD25(+/high)Foxp3(+) regulatory T cells (Treg) in
      the tumor, which might have a role in tumor progression in these animals.
      Nevertheless, for those animals that received the cytokine as part of the vaccine
      formulation, the overall effect was improved immune response and less
      disseminated disease, suggesting that therapeutic vaccination overcomes the
      potential detrimental effect of intratumoral Treg cells. Overall, the results
      presented here show that a simple vaccine formulation, that can be easily
      prepared under GMP conditions, is a promising strategy to be used in B-cell
      lymphoma and may have enough merit to be tested in clinical trials.

PMID- 19768459
TI  - Fatal pneumocystis jiroveci pneumonia in ABVD-treated Hodgkin lymphoma patients.

PMID- 19768460
TI  - Phase I study of combination therapy with weekly paclitaxel and cyclophosphamide
      for advanced or recurrent breast cancer.
AB  - PURPOSE: Although anthracycline is a key agent in breast cancer treatment, its
      use is associated with the risk of cardiotoxicity. Recently, the value of
      combination therapy with docetaxel and cyclophosphamide was reported. Because the
      characteristics of paclitaxel differ on weekly versus tri-weekly administration,
      such as in the induction of apoptosis and anti-angiogenic activity, establishment
      of a treatment regimen with a combination of paclitaxel and cyclophosphamide (PC)
      is warranted. We initiated a phase I study to determine the maximum tolerated
      dose (MTD) and recommended dose (RD) of combination therapy with PC for advanced
      or recurrent breast cancer. PATIENTS AND METHODS: Eligible patients had advanced
      or recurrent breast cancer. Paclitaxel was given intravenously on days 1, 8, and
      15 of every 3-week course, and cyclophosphamide on day 1, over a total of four
      courses. Paclitaxel was given at 80 mg/m(2) for level 1 and 100 mg/m(2) for level
      2, and cyclophosphamide at 600 mg/m(2) in both cases. Onset of dose-limiting
      toxicity was evaluated during the first course, and tolerability throughout the
      four courses. RESULTS: Four patients were enrolled in each of levels 1 and 2 from
      October 2006 to November 2007. The main toxicities were grade 3 neutropenia in
      four patients (50%) and sensory neuropathy in one (12.5%). An MTD was not
      attained, as neither a hematologic toxicity of grade 4 nor a non-hematologic
      toxicity of grade 3 or higher was observed during the first course at level 1 or
      2. Response rate amongst assessable patients (one in level 1, two in level 2) was
      66.7%. CONCLUSIONS: Safety was well tolerated throughout the four courses at
      level 2, and this dosage level was therefore regarded as the RD.

PMID- 19768461
TI  - Metabolism of sulphonated anthraquinones in rhubarb, maize and celery: the role
      of cytochromes P450 and peroxidases.
AB  - Sulphonated anthraquinones are precursors of many synthetic dyes and pigments,
      recalcitrant to biodegradation, and thus contaminating many industrial effluents
      and rivers. In the development of a phytotreatment to remove sulphonated aromatic
      compounds, rhubarb (Rheum rhaponticum), a plant producing natural anthraquinones,
      as well as maize (Zea mays) and celery (Apium graveolens), plants not producing
      anthraquinones, were tested for their ability to metabolise these xenobiotics.
      Plants were cultivated under hydroponic conditions, with or without sulphonated
      anthraquinones, and were harvested at different times. Either microsomal or
      cytosolic fractions were prepared. The monooxygenase activity of cytochromes P450
      towards several sulphonated anthraquinones was tested using a new method based on
      the fluorimetric detection of oxygen consumed during cytochromes P450-catalysed
      reactions. The activity of cytosolic peroxidases was measured by
      spectrophotometry, using guaiacol as a substrate. Results indicated that the
      activity of cytochromes P450 and peroxidases significantly increased in rhubarb
      plants cultivated in the presence of sulphonated anthraquinones. A higher
      activity of cytochromes P450 was also detected in maize and celery exposed to the
      pollutants. In these two plants, a peroxidase activity was also detected, but
      without a clear difference between the control plants and the plants exposed to
      the organic contaminants. This research demonstrated the existence in rhubarb,
      maize and celery of biochemical mechanisms involved in the metabolism and
      detoxification of sulphonated anthraquinones. Taken together, results confirmed
      that rhubarb might be the most appropriate plant for the phytotreatment of these
      organic pollutants.

PMID- 19768462
TI  - Characterization of bovine fetal Leydig cells by KIT expression.
AB  - The origin of fetal Leydig cells (FLC) and whether they share a common lineage
      with adult Leydig cells (ALC) is still under debate, and a marker to reliably
      track and isolate fetal Leydig precursor cells remains to be identified. We
      analyzed KIT positive (KIT+) cells in gonads from bovine fetuses with crown-rump
      length (CRL) 2.5-85 cm by immunohistochemistry, and found that KIT expression was
      gender-specific. In female gonads, expression was mainly associated with
      epithelial cell cords, which extended from the surface epithelium towards the KIT
      negative inner stroma. In male gonads of fetuses, after CRL 2.9 cm, KIT
      expression was strikingly strong in interstitial cells (IC). Only a few KIT+
      cells were detected in the epithelial cell cords and in the stromal layer under
      the surface epithelium after CRL 3.5 cm. In the male fetuses, KIT expression in
      IC was a continuous and characteristic feature until full term. At all
      developmental stages KIT+ areas alternated with anti-Mullerian hormone-positive
      areas. Platelet-derived growth factor receptor alpha production was initiated
      after the expression of KIT at CRL 4.5 cm. Detection of cytochrome P450 side
      chain cleavage enzyme and steroidogenic acute regulatory protein in KIT+ IC
      identified them as FLC. KIT+ cells, isolated from testes by magnetic-activated
      cell sorting, retained their steroidogenic capacity in vitro. Together, these
      findings show that KIT+ IC of fetal testis correspond to FLC, which can be
      successfully cultivated for advanced studies.

PMID- 19768463
TI  - Selection of buffer pH by the isoelectric point of the antigen for the efficient
      heat-induced epitope retrieval: re-appraisal for nuclear protein pathobiology.
AB  - Epitope retrieval (ER) using heating causes a dramatic improvement in the
      sensitivity of immunohistochemistry for formalin-fixed paraffin-embedded (FFPE)
      tissue sections. Here, the relationship between the pH of the retrieval buffer
      used for heat-induced epitope retrieval (HIER) and the isoelectric points (pI) of
      the antigen recognized by antibodies against nuclear proteins (mainly human
      pituitary transcription factors in this study) was investigated using FFPE tissue
      sections. A universal buffer, with a buffering capacity over a wide pH range from
      2.0 to 12.0, was used for HIER. We found that the intensity of staining for most
      nuclear proteins after HIER depended simply on the pH of the buffer. Importantly,
      for efficient HIER, antigens with acidic pI required basic pH buffer conditions,
      while antigens with alkaline pI required acidic conditions. This implies that the
      electrostatic charge of the antigens contributed significantly to the efficiency
      of HIER. We conclude that appropriate selection of the pH of the buffer based on
      the pI of the individual antigens is of great importance for efficient ER. It is
      concluded that the mechanism of HEIR may, therefore, depend to a large extent on
      the pI of the antigen under investigation.

PMID- 19768464
TI  - Bilateral deficit and EMG activity during explosive lower limb contractions
      against different overloads.
AB  - We investigated whether bilateral deficit (BLD): (1) is observed during explosive
      lower limb contractions; (2) can be attributed to a reduction of neural drive
      and/or (3) to a different muscle coordination, and/or (4) to changes of the
      muscle force-velocity (F-v) relationship. Ten volunteers performed maximal
      explosive efforts of approximately 450 ms on a sledge ergometer, with both lower
      limbs (BL), with the right and left limb separately (ML), against different
      overloads. Peak-force (F, N), peak-power (w, W), sledge peak-velocity (v, m/s)
      and electromyography (EMG) of vastus lateralis (VL), rectus femoris (RF), biceps
      femoris (BF) and gastrocnemius medialis (GM) were recorded. Average values over
      the six overloads of F and w, developed by right or left limb during BL, were
      significantly lower (883 +/- 200 and 918 +/- 141 N; 1089 +/- 407 and 1099 +/- 325
      W) than those developed during ML contractions (1285 +/- 177 and 1306 +/- 147 N;
      1536 +/- 408 and 1497 +/- 392 W). VL and RF iEMGs were lower in BL than in ML (74
      +/- 28 vs. 91 +/- 21% MVC and 39 +/- 21 vs. 56 +/- 28% MVC). The coordination
      among the four muscles, as determined from an analysis of the time course of
      iEMG, expressed as percentage of that attained at the end of the push, was poorer
      in BL, as compared to ML. BL F-v curves were different as compared to the ML
      ones, the force and power developed, at a given v, being significantly larger in
      ML. It is concluded that BLD occurs also during explosive pushes with the lower
      limbs, and that it is mainly due to different muscle coordination.

PMID- 19768467
TI  - Transmural expression of ion channels and transporters in human nondiseased and
      end-stage failing hearts.
AB  - The cardiac action potential is primarily shaped by the orchestrated function of
      several different types of ion channels and transporters. One of the regional
      differences believed to play a major role in the progression and stability of the
      action potential is the transmural gradient of electrical activity across the
      ventricular wall. An altered balance in the ionic currents across the free wall
      is assumed to be a substrate for arrhythmia. A large fraction of patients with
      heart failure experience ventricular arrhythmia. However, the underlying
      substrate of these functional changes is not well-established as expression
      analyses of human heart failure (HF) are sparse. We have investigated steady
      state RNA levels by quantitative polymerase chain reaction of ion channels,
      transporters, connexin 43, and miR-1 in 11 end-stage HF and seven nonfailing (NF)
      hearts. The quantifications were performed on endo-, mid-, and epicardium of left
      ventricle, enabling us to establish changes in the transmural expression
      gradient. Transcripts encoding Cav1.2, HCN2, Kir2.1, KCNE1, SUR1, and NCX1 were
      upregulated in HF compared to NF while a downregulation was observed for KChIP2,
      SERCA2, and miR-1. Additionally, the transmural gradient of KCNE1, KChIP2,
      Kir6.2, SUR1, Nav1.5, NCX1, and RyR2 found in NF was only preserved for KChiP2
      and Nav1.5 in HF. The transmural gradients of NCX1, Nav1.5, and KChIP2 and the
      downregulation of KChIP2 were confirmed by Western blotting. In conclusion, our
      results reveal altered expression of several cardiac ion channels and
      transporters which may in part explain the increased susceptibility to arrhythmia
      in end-state failing hearts.

PMID- 19768466
TI  - Epigenetic factors in aging and longevity.
AB  - Epigenetics refers to phenotypic changes caused by mechanisms that are unrelated
      to changes in the underlying DNA sequence, most notably chromatin remodeling
      driven by histone modifications, and DNA methylation. Such variation is
      transmitted by cell division, but generally not passed on through the germ line.
      An increasing body of evidence supports a role for epigenetic changes in the
      etiology of aging and its associated disease sequelae. Here, we review the role
      of epigenetics in aging and longevity with a focus on DNA methylation. Increased
      understanding of those aging-related processes that are driven by epigenetic
      mechanisms will allow for the development of novel epigenetic-based diagnostic,
      preventive, and therapeutic strategies for age-related diseases.

PMID- 19768468
TI  - Measuring health-related quality of life in Hungarian children attending a
      cardiology clinic with the Pediatric Quality of Life Inventory.
AB  - The aim of the study was to evaluate health-related quality of life (HRQoL) of
      Hungarian children attending a pediatric cardiology outpatient unit with the
      Pediatric Quality of Life Inventory (PedsQL) questionnaire. The PedsQL Generic
      Core Scales and Cardiac Module were administered to 254 families including 195
      children during a pediatric cardiology outpatient visit, and 525 families
      including 373 children from the general population were examined by the PedsQL
      Generic Core Scale by a postal survey. The relationships between PedsQL scores
      and patient characteristics were analyzed. Hungarian children attending a
      cardiology outpatient unit as an entire group and patients with severe heart
      diseases report significantly lower physical functioning than the general
      population, while more HRQoL dimensions are negatively affected according to the
      parents' opinion. Children with congenital heart disease of mild and great
      complexity also report impaired psychosocial functioning. HRQoL impairment is
      concentrated to the age of 5-7 years. Comparing our results with previous ones on
      U.S. pediatric cardiologic samples, we found significantly lower scores mainly
      for the physical functioning and heart symptoms subscales. This HRQoL study with
      an internationally well-validated instrument on children with heart disease in a
      Central European country highlights certain aspects of the health-care system and
      brings the possibility for the assessment of pediatric cardiology outcomes in a
      more comprehensive way.

PMID- 19768469
TI  - The interaction of temperature, water availability and fire cues regulates seed
      germination in a fire-prone landscape.
AB  - Ambient temperature and water availability regulate seasonal timing of
      germination. In fire-prone landscapes, the role of fire-related cues in affecting
      the range of temperatures and water potentials (psis) across which germination
      can occur is poorly known, especially in non-Mediterranean landscapes. We
      examined interactive effects of temperature (15 or 25 degrees C), psi (0 to -0.9
      MPa), and fire-related cues (heat and smoke) on germination for seeds of three
      shrub species from fire-prone southeastern Australia. Incubation temperature
      affected germination of untreated seeds of Kunzea ambigua and Kunzea capitata
      (Myrtaceae) (reduction at 25 degrees C), but germination was uniformly low in
      Epacris obtusifolia (Ericaceae). Decreasing psi reduced germination across both
      incubation temperatures. Fire cues increased germination at both incubation
      temperatures and across psis, although in Kunzea the increase was smaller and
      occurred over a narrower range of psis at 25 degrees C. Hydrotime analysis
      suggested that fire cues reduced the amount of water necessary for germination of
      Kunzea seeds. Post-fire germination of the three study species may occur during
      the warm season, although it is reduced and confined to wet periods for the two
      Kunzea species. Warm season germination of the study species is consistent with a
      trade-off between the increased risk of failure of a cohort of seedlings, and
      benefits of early establishment of a cohort that may survive in an environment
      with aseasonal rainfall.

PMID- 19768470
TI  - Sensitivity of Daphnia species to phosphorus-deficient diets.
AB  - The life history of freshwater cladocerans such as Daphnia spp. is strongly
      affected by their environment. Factors such as temperature, food quantity and
      even the presence or absence of predators influence growth, reproduction and
      morphology of individuals. Recently, it has also become clear that the quality of
      the food can affect various life history traits of Daphnia. More specifically,
      the effect of the elemental composition of algae, expressed as the C:P ratio, has
      been studied intensively. Daphnia species differ in their response to differences
      in the C:P ratio of their food. Until now, it has been unclear whether these
      species differences are driven by phylogenetic constraints or by adaptation to
      particular environmental conditions. Here we present laboratory experiments with
      12 Daphnia species from three different subgenera originating from a broad range
      of habitats. We compared somatic growth rates and sensitivity to variation in the
      nutrient stoichiometry of the food with habitat parameters, taking into account
      the phylogenetic history of the species. No associations between fitness and
      habitat parameters were detected. However, we found a trade-off between
      sensitivity to P-deficient diets and the maximum growth rate on a P-sufficient
      diet. In several cases, this trade-off helps to explain the association between
      species distribution and habitat parameters. We observed no correlation of the
      sensitivity to P limitation with the phylogenetic history of the genus Daphnia.
      Thus, we conclude that the differential responses among Daphnia species to
      variation in P content in food were driven mainly by adaptations to their local
      habitats, and are not constrained by deep evolutionary patterns.

PMID- 19768471
TI  - Production of D-arabitol by a newly isolated Kodamaea ohmeri.
AB  - A new yeast, isolated from natural osmophilic sources, produces D-arabitol as the
      main metabolic product from glucose. According to 18S rRNA analysis, the NH-9
      strain belongs to the genus Kodamaea. The optimal culture conditions for inducing
      production of D-arabitol were 37 degrees C, neutral pH, 220 rpm shaking, and 5%
      inoculum. The yeast produced 81.2 +/- 0.67 g L(-1) D-arabitol from 200 g L(-1) D
      glucose in 72 h with a yield of 0.406 g g(-1) glucose and volumetric productivity
      Q(P) of 1.128 g L(-1) h(-1). Semi-continuous repeated-batch fermentation was
      performed in shaker-flasks to enhance the process of D-arabitol production by
      Kodamaea ohmeri NH-9 from D-glucose. Under repeated-batch culture conditions, the
      highest volumetric productivity was 1.380 g L(-1) h(-1).

PMID- 19768472
TI  - Cisplatin interaction with phosphatidylserine bilayer studied by solid-state NMR
      spectroscopy.
AB  - Cisplatin [cis-diamminedichloridoplatinum(II)] is used in chemotherapy where
      platinum-DNA adducts initiate tumor cell death. It is possible that side effects
      such as neurotoxicity and cellular cisplatin resistance can be due to interaction
      of cisplatin with lipids and the phospholipid bilayer. In this study, (13)C,
      (31)P, and (15)N solid-state NMR spectra of 1-palmitoyl-2-oleoyl
      phosphatidylserine (POPS) bilayers, POPS bilayers with 10 mol% cisplatin, and
      POPS bilayers with 30 mol% cisplatin were acquired. In addition, (15)N{(31)P}
      rotational echo double resonance spectra of POPS bilayers with 30 mol% cisplatin
      were acquired. The data demonstrate that the serine head group of
      phosphatidylserine binds to the aquated form of cisplatin and that cisplatin
      release of ammine takes place. It appears that the cisplatin release of ammine is
      followed by another cisplatin-POPS complex formation, possibly with cisplatin
      binding to one of the oxygen atoms of the POPS phosphate moiety.

PMID- 19768473
TI  - A combined computational and experimental investigation of the [2Fe-2S] cluster
      in biotin synthase.
AB  - Biotin synthase was the first example of what is now regarded as a distinctive
      enzyme class within the radical S-adenosylmethionine superfamily, the members of
      which use Fe/S clusters as the sulphur source in radical sulphur insertion
      reactions. The crystal structure showed that this enzyme contains a [2Fe-2S]
      cluster with a highly unusual arginine ligand, besides three normal cysteine
      ligands. However, the crystal structure is at such a low resolution that neither
      the exact coordination mode nor the role of this exceptional ligand has been
      elucidated yet, although it has been shown that it is not essential for enzyme
      activity. We have used quantum refinement of the crystal structure and combined
      quantum mechanical and molecular mechanical calculations to explore possible
      coordination modes and their influences on cluster properties. The investigations
      show that the protonation state of the arginine ligand has little influence on
      cluster geometry, so even a positively charged guanidinium moiety would be in
      close proximity to the iron atom. Nevertheless, the crystallised enzyme most
      probably contains a deprotonated (neutral) arginine coordinating via the NH
      group. Furthermore, the Fe...Fe distance seems to be independent of the
      coordination mode and is in perfect agreement with distances in other
      structurally characterised [2Fe-2S] clusters. The exceptionally large Fe...Fe
      distance found in the crystal structure could not be reproduced.

PMID- 19768474
TI  - Quantum chemical investigation of intramolecular thione-thiol tautomerism of
      1,2,4-triazole-3-thione and its disubstituted derivatives.
AB  - The one step intramolecular thione-thiol tautomerism of 1,2,4-triazole-3-thione
      and its disubstituted derivatives has been studied through the use of electronic
      structure methods. Due to the absence of experimental data for the parent
      molecule of 1,2,4-triazole-3-thione the structure and energetics of
      aforementioned tautomers were derived using various basis sets and levels
      including HF, B3LYP, and MP2 methods. The gas phase results show that in all
      different levels of theory the most stable tautomer is the thione form. It has
      also been revealed that B3LYP/6-31G(d,p) level is quite well suited and reliable
      to investigate these kinds of tautomerism. To account the influence of
      substituents on the mentioned tautomerization, the tautomerism and conformational
      properties as well as vibrational analysis of 20 halophenyl and isopyridyl
      derivatives were investigated using B3LYP/6-31G(d,p) calculations. In all cases
      the calculations indicate that substituents have no considerable effects on
      relative stabilities and energy barriers for the thione-thiol proton transfer and
      the thione forms are the predominant species in the gas phase. In order to figure
      out the relative stabilities of the species involved in the tautomerism,
      geometrical and natural bond orbital (NBO) analyses have been employed. It has
      also been shown that the computed vibrational frequencies of tautomers with
      different scaling factors could be used to interpret the vibrational frequencies
      in IR spectrum of similar species.

PMID- 19768475
TI  - Ethanol and xylitol production from glucose and xylose at high temperature by
      Kluyveromyces sp. IIPE453.
AB  - A yeast strain Kluyveromyces sp. IIPE453 (MTCC 5314), isolated from soil samples
      collected from dumping sites of crushed sugarcane bagasse in Sugar Mill, showed
      growth and fermentation efficiency at high temperatures ranging from 45 degrees C
      to 50 degrees C. The yeast strain was able to use a wide range of substrates,
      such as glucose, xylose, mannose, galactose, arabinose, sucrose, and cellobiose,
      either for growth or fermentation to ethanol. The strain also showed xylitol
      production from xylose. In batch fermentation, the strain showed maximum ethanol
      concentration of 82 +/- 0.5 g l(-1) (10.4% v/v) on initial glucose concentration
      of 200 g l(-1), and ethanol concentration of 1.75 +/- 0.05 g l(-1) as well as
      xylitol concentration of 11.5 +/- 0.4 g l(-1) on initial xylose concentration of
      20 g l(-1) at 50 degrees C. The strain was capable of simultaneously using
      glucose and xylose in a mixture of glucose concentration of 75 g l(-1) and xylose
      concentration of 25 g l(-1), achieving maximum ethanol concentration of 38 +/-
      0.5 g l(-1) and xylitol concentration of 14.5 +/- 0.2 g l(-1) in batch
      fermentation. High stability of the strain was observed in a continuous
      fermentation by feeding the mixture of glucose concentration of 75 g l(-1) and
      xylose concentration of 25 g l(-1) by recycling the cells, achieving maximum
      ethanol concentration of 30.8 +/- 6.2 g l(-1) and xylitol concentration of 7.35
      +/- 3.3 g l(-1) with ethanol productivity of 3.1 +/- 0.6 g l(-1) h(-1) and
      xylitol productivity of 0.75 +/- 0.35 g l(-1) h(-1), respectively.

PMID- 19768476
TI  - Hereditary influences in oxygen-induced retinopathy in the rat.
AB  - Rodent models of oxygen-induced retinopathy (OIR) provide important insights into
      the pathogenesis of human retinopathy of prematurity. Herein, we present an
      overview of our work with rat OIR to date. We have identified marked and
      consistent variations in susceptibility to OIR amongst different inbred rat
      strains and provide strong evidence for a genetic determinant of susceptibility
      to OIR. Furthermore, we have characterised differences in retinal angiogenic
      factor gene expression amongst different inbred rat strains exposed to cyclic
      hyperoxia. A key determinant of susceptibility to OIR appears to be the extent to
      which pro-angiogenic factor genes, such as vascular endothelial growth factor and
      erythropoietin, are expressed during the period of hyperoxic exposure. Those
      strains in which expression is relatively well maintained are less susceptible to
      retinopathy than are those in which expression is reduced. In addition, we
      identify an association between ocular pigmentation and OIR susceptibility.

PMID- 19768477
TI  - Special considerations for obstructive sleep apnea in women.

PMID- 19768478
TI  - Changes in oil content of transgenic soybeans expressing the yeast SLC1 gene.
AB  - The wild type (Wt) and mutant form of yeast (sphingolipid compensation) genes,
      SLC1 and SLC1-1, have been shown to have lysophosphatidic acid acyltransferase
      (LPAT) activities (Nageic et al. in J Biol Chem 269:22156-22163, 1993).
      Expression of these LPAT genes was reported to increase oil content in transgenic
      Arabidopsis and Brassica napus. It is of interest to determine if the TAG content
      increase would also be seen in soybeans. Therefore, the wild type SLC1 was
      expressed in soybean somatic embryos under the control of seed specific phaseolin
      promoter. Some transgenic somatic embryos and in both T2 and T3 transgenic seeds
      showed higher oil contents. Compared to controls, the average increase in
      triglyceride values went up by 1.5% in transgenic somatic embryos. A maximum of
      3.2% increase in seed oil content was observed in a T3 line. Expression of the
      yeast Wt LPAT gene did not alter the fatty acid composition of the seed oil.

PMID- 19768479
TI  - WITHDRAWN: Missed Monteggia fracture in children: is annular ligament
      reconstruction always required?
AB  - Ahead of Print article withdrawn by publisher.

PMID- 19768480
TI  - Intravascular ultrasound radiofrequency analysis of the lesion segment profile in
      ACS patients.
AB  - BACKGROUND: Intravascular ultrasound radiofrequency analysis (IVUS-RF)
      characterizes plaque components as necrotic core (NC) and dense calcium (DC). The
      aim of this study was to perform an IVUS-RF derived analysis of the lesion
      segment profile in acute coronary syndrome (ACS) patients. Therefore, we compared
      the site of the minimum lumen area--cross sectional area (mla-CSA) with the worst
      lesion site--CSA (ws-CSA) defined by the maximum NC site. METHODS: We performed
      IVUS-RF derived plaque composition and plaque-type classification analysis in 48
      ACS patients with 48 culprit (CL) and 69 non-culprit lesions (NCL). RESULTS: The
      plaque dimension of the mla- and ws-CSA was significantly different regarding the
      lumen area (5.18 +/- 2.09 mm2 vs. 6.72 +/- 2.73 mm2, p = 0.0013) and the vessel
      area (14.80 +/- 5.86 mm2 vs. 17.15 +/- 4.94 mm2, p = 0.0142). The absolute plaque
      composition was also significantly different regarding the DC tissue (0.71 +/-
      0.57 mm2 vs. 0.98 +/- 0.54 mm2, p = 0.0102) and the NC tissue (1.41 +/- 1.28 mm2
      vs. 1.85 +/- 1.37 mm2, p = 0.0469). The plaque-type classification revealed
      significantly more thin cap fibroatheroma (TCFA) lesions at the ws-CSA compared
      to the mla-CSA (n = 53/89.8% vs. n = 26/44.1%, p < 0.0001). In the majority of
      the CL and NCL lesion segments the ws-CSA was located proximal to the mla-CSA
      compared to the distal location (n = 65/55.6% vs. n = 23/19.7%). CONCLUSIONS: In
      the majority of the lesion segments in ACS patients the ws-CSA is not identical
      with the mla-CSA. The ws-CSA compared to mla-CSA presented with significantly
      more NC and DC tissue resulting in a higher amount of TCFA lesions.

PMID- 19768481
TI  - Neuropsychological functioning in early-onset first-episode psychosis: comparison
      of diagnostic subgroups.
AB  - The aims of this study were to examine the nature and extent of cognitive
      impairment in first-episode early-onset psychosis (FE-EOP) soon after their
      stabilisation and to search for potential differences according to specific
      diagnostic sub-groups of patients. As part of a Spanish multicentre longitudinal
      study, 107 FE-EOP patients and 98 healthy controls were assessed on the following
      cognitive domains: attention, working memory, executive functioning, and verbal
      learning and memory. Three diagnostic categories were established in the patient
      sample: schizophrenia (n = 36), bipolar disorder (n = 19), and other psychosis (n
      = 52). Patients performed significantly worse than controls in all cognitive
      domains. The three diagnostic sub-groups did not differ in terms of
      impaired/preserved cognitive functions or degree of impairment. FE-EOP patients
      show significant cognitive impairment that, during this early phase, seems to be
      non-specific to differential diagnosis.

PMID- 19768482
TI  - Neuromyelitis and more: the unfolding spectrum of aquaporin  4-related
      neurological diseases.

PMID- 19768483
TI  - Complex phenotype in an Italian family with a novel mutation in SPG3A.
AB  - Mutations in the SPG3A gene represent a significant cause of autosomal dominant
      hereditary spastic paraplegia with early onset and pure phenotype. We describe an
      Italian family manifesting a complex phenotype, characterized by cerebellar
      involvement in the proband and amyotrophic lateral sclerosis-like syndrome in her
      father, in association with a new mutation in SPG3A. Our findings further widen
      the notion of clinical heterogeneity in SPG3A mutations.

PMID- 19768484
TI  - Lissencephaly, IgG subclass immunodeficiency, and a connective tissue disorder: a
      new syndrome?

PMID- 19768486
TI  - Larval responses of three midwestern anurans to chronic, low-dose exposures of
      four herbicides.
AB  - Low levels of agricultural herbicides often contaminate surface water and might
      persist throughout the growing season, potentially acting as stressors on aquatic
      organisms. Although low-dose, chronic exposures to agrochemicals are likely
      common for many nontarget organisms, studies addressing these effects using end
      use herbicide formulations are rare. We exposed three common species of tadpoles
      to conservative levels of atrazine, S-metolachlor, and glyphosate end-use
      herbicide formulations throughout the larval period to test for survival
      differences or life-history trait alterations. Exposure to the glyphosate product
      Roundup WeatherMax at 572 ppb glyphosate acid equivalents (a.e.) resulted in 80%
      mortality of western chorus frog tadpoles, likely as a result of a unique
      surfactant formulation. Exposure to WeatherMax or Roundup Original Max at 572 ppb
      a.e. also lengthened the larval period for American toads. Chronic atrazine and S
      metolachlor exposures induced no significant negative effects on survival, mass
      at metamorphosis, or larval period length at the levels tested. These results
      highlight the importance of explicitly tying chronic tests to the natural
      environment and considering contributions of surfactant/adjuvant components to
      end-use formulation toxicities, even between very similar products.

PMID- 19768487
TI  - Rare association of tracheal diverticulum with pulmonary artery sling and
      aberrant right subclavian artery.
AB  - Tracheal diverticulum is a rarely encountered entity characterized by single or
      multiple invaginations of the tracheal wall. Two types of tracheal diverticula
      exist: congenital and acquired. We report a case of a pulmonary artery sling with
      an aberrant right subclavian artery associated with tracheal diverticulum.

PMID- 19768488
TI  - Pacemaker upgrade causing new-onset heart failure in a patient with complete
      congenital atrioventricular block.
AB  - For infants with congenital complete atrioventricular block (CCAVB), the choice
      of pacing modalities is limited. Due to their size and surgical limitations,
      neonates typically start with an epicardial right ventricular pacing system, then
      upgrade to right-sided dual-chamber pacing once appropriate size is achieved.
      These modes are generally well tolerated. However, the reported case involved a
      patient with CCAVB who paradoxically experienced congestive heart failure after
      upgrading to a dual-chamber system, a theoretically superior pacing modality.
      With conversion to biventricular pacing, a relatively new modality for adults
      with very little pediatric experience to date, the patient's symptoms
      dramatically improved.

PMID- 19768490
TI  - Crohn's disease: multi-detector row CT-enteroclysis appearance of the appendix.
AB  - The objective of our retrospective study was to determine the MDCT-enteroclysis
      appearance of the appendix in patients with Crohn's disease and to correlate this
      appearance with the status of the disease. We reviewed the MDCT-enteroclysis
      examinations of 76 patients with Crohn's disease. Images were analyzed for
      visualization of the appendix, largest axial diameter of the appendix and degrees
      of enhancement. Findings were correlated with the status of the disease (active
      vs. nonactive) and compared with those observed in a control group. Among the
      various variables, hyperenhancement of the appendiceal wall was found in 18.9% of
      patients with active disease and in no patients with inactive disease nor in the
      control group (P = 0.0023). This sign had a specificity of 100% for
      differentiating between active and inactive Crohn's disease. We conclude that
      increased appendiceal wall enhancement is, at a statistically significant level,
      more frequently observed in patients with active Crohn's disease by comparison
      with patients with inactive disease and control subjects. This result suggests
      that this finding may be used as an additional MDCT-enteroclysis finding to
      determine the activity of the disease.

PMID- 19768489
TI  - Synergistic effects of elevated systolic blood pressure and hypercholesterolemia
      on carotid intima-media thickness in children and adolescents.
AB  - This study aimed to investigate the synergistic effects of elevated systolic
      blood pressure (SBP) and hypercholesterolemia on carotid intima-media thickness
      (cIMT). For this study, 60 children with hypercholesterolemia and 40 healthy
      control children were divided into four subgroups: hypercholesterolemic children
      with normal (<90th percentile) or elevated (>or= 90th percentile) SBP and control
      children with normal or elevated SBP. The highest mean and maximal cIMT values
      were found in the hypercholesterolemic children with elevated SBP and were
      significantly different from those of all the other groups. The synergistic
      effects of elevated SBP and hypercholesterolemia lead to a significant increase
      in cIMT as a subclinical sign of early atherosclerosis.

PMID- 19768491
TI  - Late-onset pulmonary edema and disseminated intravascular coagulation due to
      latex anaphylaxis.
AB  - BACKGROUND: Anaphylaxis after the administration of tissue expanders has been
      reported. Late onset hypotension, thrombocytopenia, disseminated intravascular
      coagulation (DIC) and pulmonary edema due to the tissue expanders have not been
      reported. METHODS: In this case report, late onset hypotension, thrombocytopenia,
      disseminated intravascular coagulation and pulmonary edema due to the
      administration of tissue expanders were described. RESULTS: The authors report a
      16-year-old girl with burn scar deformities scheduled for reconstruction of the
      scar contractures with insertion of tissue expanders in which the administration
      of latex tissue expanders was associated with late onset hypotension,
      thrombocytopenia, disseminated intravascular coagulation and pulmonary edema.
      Skin tests performed for latex demonstrated strong positive weal and flare
      reactions. CONCLUSION: Late onset anaphylactic reactions due to latex tissue
      expanders, an unusual unpredictable adverse reaction, must be kept in mind. Early
      recognition and proper emergent treatment are essential to reversing this
      complication.

PMID- 19768494
TI  - Abdominoplasty: same classification and a new treatment concept 20 years later.
AB  - Twenty years after my first paper on abdominoplasty, I find that the
      classification of abdominoplasty remains the same, but new operative techniques
      allow for accentuated improvement of the results through more liposuction, less
      undermining in tunnels, and reduction of skin traction. I use the same
      classification of diagnoses proposed in 1988, dividing the aesthetic alterations
      into five groups, and describe my experience during a 6-year period with 502
      patients. I used vibroliposuction and performed plicature of the muscular
      aponeurosis through tunnels (where there are no important muscular perforator
      vessels), without damaging the vascularization. I propose an appropriate ratio of
      1/1.5 between infra- and supraumbilical segments for uses in diagnosis and
      treatment, and the same ratio between the perimeter of the waist and the hips up
      to 1/1.618, known as the golden or divine proportion. According to this new
      treatment concept, vibroliposuction is used in GI. Vibroliposuction and
      suprapubic fusiform skin resection with an indigenous canoe shape are used in
      GII. Vibroliposuction, fusiform skin resection, and plicature of the external
      oblique muscle aponeurosis through two lateral tunnels are used in GIII.
      Vibroliposuction, fusiform skin resection, plicature of the rectus muscles
      aponeurosis through a medial tunnel, and detachment of the umbilicus aponeurotic
      implantation and reattachment in a maximum proportion of 1/1.6 between the infra-
      and supraumbilical skin segment with a bolster stitch are used in GIV. In GV, all
      the infraumbilical skin and a subcutaneous segment are removed after
      vibroliposuction, then a median tunnel from the umbilicus to the xiphoid process
      and a plicature of the rectus muscle aponeurosis from the pubis to the xiphoid
      process are made, and then the umbilicus is transposed. When necessary, a
      plicature of the oblique external muscle aponeurosis through two lateral tunnels
      is made resulting in three tunnels.

PMID- 19768493
TI  - Improvement in quality of life and self-esteem after breast reduction surgery.
AB  - BACKGROUND: Breast reduction surgery is sought by patients who have physical and
      psychological symptoms. This study assessed the quality of life and self-esteem
      before and after breast reduction surgery. METHODS: Thirty patients with a
      diagnosis of mammary hypertrophy who were consecutively selected to undergo
      breast reduction and aged between 18 and 54 years (mean = 32.65 years, SD = 9.87)
      participated in the study. Diagnosis was performed by breast measurements
      associated with symptoms related to excessive breast size. Patients completed the
      SF-36 Quality of Life Inventory and Rosenberg Self-Esteem Scale before the
      procedure and 30 and 120 days after surgery. The nonparametric sign test and
      Fisher's exact test were used to analyze the data. RESULTS: There was significant
      improvement (p < or = 0.05) in all domains of quality of life and in self-esteem
      when scores before and after surgery were compared. CONCLUSION: Both self-esteem
      and quality of life significantly improved after breast reduction surgery.

PMID- 19768492
TI  - Soft tissue diagnosis in maxillofacial surgery: a preliminary study on three
      dimensional face geometrical features-based analysis.
AB  - To obtain the best surgical results in orthognathic surgery, treatment planning
      and evaluation of results should be performed. In these operations it is
      necessary to provide the physician with powerful tools that can underline the
      behavior of soft tissue. For this reason, considering the improvements provided
      by the use of 3D scanners in medical diagnosis, we propose a methodology for
      analyzing facial morphology working with geometrical features. The methodology
      has been tested on patients with malocclusion in order to analyze the reliability
      and efficiency of the provided diagnostic results.

PMID- 19768495
TI  - Vertebral arteriovenous fistula presenting as cervical myelopathy: a rapid
      recovery with balloon embolization.
AB  - A 24-year-old male presented with progressive cervical myelopathy of 2 months'
      duration. Magnetic resonance imaging of the cervical spine and angiography
      revealed a large arteriovenous fistula arising from the left vertebral artery.
      The present case highlights the clinical features and dramatic recovery following
      endovascular balloon occlusion of a giant cervical arteriovenous fistula.

PMID- 19768496
TI  - A right common iliac artery pseudoaneurysm with an iliac-caval arteriovenous
      fistula: a rare complication of the Recovery vena cava filter.

PMID- 19768497
TI  - A retrospective comparative study of tunneled haemodialysis catheters inserted
      through occluded or collateral veins versus conventional methods.
AB  - Tunneled hemodialysis catheters become essential in dialysis access when there is
      no possibility of using a functioning arteriovenous fistula. Collateral or
      occluded veins visible on ultrasound are used for puncture and passage of
      catheters into the central venous system. Chronically occluded veins are crossed
      with guidewires to allow dilatation and subsequent passage of hemodialysis
      catheters. We performed a retrospective analysis of patient demographics,
      comorbidities, procedural complications, functional survival, performance, and
      history of previous vascular access. The study group was compared with two
      control groups in which dialysis catheters were inserted either by radiologists
      in the interventional suite or by clinicians on the wards. Nineteen patients from
      the study group were compared with same number of patients in both control
      groups. The mean age of the study group was higher compared with the control
      groups. There was no significant difference in mean functional survival,
      infection rates, dialysis pump speeds in the first 2 weeks, and procedural
      complications between the study group and the controls. The study group had a
      significantly higher number of previous vascular access interventions, longer
      dialysis careers, and more comorbidities. Tunneled dialysis catheter placement by
      way of collateral or occluded veins appears safe and effective. These techniques
      give the operator further options when faced with patients possessing challenging
      vascular access. Indeed, there may be a case for preferential use of these veins
      to keep patent central veins in reserve.

PMID- 19768498
TI  - Diagnosis of popliteal venous entrapment syndrome by magnetic resonance imaging
      using blood-pool contrast agents.
AB  - Popliteal vascular entrapment syndrome is caused by aberrations or hypertrophy of
      the gastrocnemius muscles, which compress the neurovascular structures of the
      popliteal fossa, leading to symptoms of vascular and degeneration as well as
      aneurysm formation. Imaging of popliteal vascular entrapment may be performed
      with ultrasound, magnetic resonance imaging (MRI), computed tomography
      angiography, and conventional angiography. The use of blood-pool contrast agents
      in MRI when popliteal vascular entrapment is suspected offers the possibility to
      perform vascular imaging with first-pass magnetic resonance angiographic, high
      resolution, steady-state imaging and allows functional tests all within one
      examination with a single dose of contrast agent. We present imaging findings in
      a case of symptomatic popliteal vein entrapment diagnosed by the use of blood
      pool contrast-enhanced MRI.

PMID- 19768499
TI  - Chordoma of the lumbar spine presenting as sciatica and treated with
      vertebroplasty.
AB  - The lumbar spine is a less common location for chordoma. Here we describe a 44
      year-old woman presenting with pain due to a L4 vertebral expansile lesion that
      caused significant canal stenosis and neural foraminal compromise. Vertebroplasty
      was performed and resulted in immediate pain relief. For patients with painful
      lumbar chordoma who are unwilling to undergo surgery, vertebroplasty can play a
      palliative role as in patients with other vertebral lesions. Treating pain and
      stabilizing vertebra by way of vertebroplasty in a case of chordoma has not yet
      been reported.

PMID- 19768500
TI  - Technique, complication, and long-term outcome for endovascular treatment of
      iliac artery occlusion.
AB  - The aim of this study was to report technical details, procedure-related
      complications, and results of endovascular treatment in chronic iliac artery
      occlusion. Between 2001 and 2008, endovascular treatments of 127 chronic iliac
      artery occlusions in 118 patients (8 women and 110 men; mean age, 59 years) were
      retrospectively reviewed. The study was based on Ad Hoc Committee on Reporting
      Standards (Society for Vascular Surgery/International Society for Cardiovascular
      Surgery Standards). All occlusions were treated with stent placement with or
      without preliminary balloon angioplasty. Kaplan-Meier estimators were used to
      determine patency rates. Univariate and multivariate analyses were performed to
      determine variables affecting successful recanalization, major complications,
      early stent thrombosis (<or=30 days), and primary and secondary patency rates.
      Initial technical success was achieved in 117 (92%) procedures. Successful
      recanalization was obtained by antegrade approach in 69 of 77 (90%) procedures
      and by retrograde approach in 52 of 105 (50%) procedures (p < 0.001).
      Complications were encountered in 28 (24%) patients [minor in 7 patients (6%) and
      major in 22 patients (19%)]. One death occurred in the operative period secondary
      to iliac artery rupture. Early stent thrombosis was seen in eight (7%) patients.
      Presence of critical limb ischemia (p = 0.03), subintimal recanalization (p =
      0.03), and major complication (p = 0.02) were the independent predictors of early
      stent thrombosis on multivariate analysis. Primary and secondary patency rates at
      5 years were 63 and 93%, respectively. Presence of critical limb ischemia, TASC
      type C iliac lesions, combined occlusions of both common and external iliac
      arteries, and major complications were associated with decreased patency rates on
      univariate analysis, whereas these factors were not independent predictors of
      stent patency on multivariate analysis. In conclusion, endovascular treatment of
      iliac artery occlusion has a high technical success rate with favorable long-term
      patency rate. Success of recanalization increases with use of the antegrade
      approach and with the presence of a stump of artery before the occlusion.

PMID- 19768501
TI  - Venous thromboembolism after removal of retrievable inferior vena cava filters.
AB  - The purpose of this study was to examine the incidence of new or recurrent venous
      thromboembolism (VTE) after retrieval of inferior vena cava (IVC) filters and
      risk factors associated with such recurrence. Between March 2001 and September
      2008, at our institution, implanted retrievable vena cava filters were retrieved
      in 76 patients. The incidence of new or recurrent VTE after retrieval was
      reviewed and numerous variables were analyzed to assess risk factors for
      redevelopment of VTE after filter retrieval. In 5 (6.6%) of the 76 patients,
      redevelopment or worsening of VTE was seen after retrieval of the filter. Three
      patients (4.0%) had recurrent deep venous thrombosis (DVT) in the lower
      extremities and 2 (2.6%) had development of pulmonary embolism, resulting in
      death. Although there was no significant difference in the incidence of new or
      recurrent VTE related to any risk factor investigated, a tendency for development
      of VTE after filter retrieval was higher in patients in whom DVT in the lower
      extremities had been so severe during filter implantation that interventional
      radiological therapies in addition to traditional anticoagulation therapies were
      required (40% in patients with recurrent VTE vs. 23% in those without VTE; p =
      0.5866 according to Fisher's exact probability test) and in patients in whom DVT
      remained at the time of filter retrieval (60% in patients with recurrent VTE vs.
      37% in those without VTE; p = 0.3637). In conclusion, new or recurrent VTE was
      rare after retrieval of IVC filters but was most likely to occur in patients who
      had severe DVT during filter implantation and/or in patients with a DVT that
      remained at the time of filter retrieval. We must point out that the fatality
      rate from PE after filter removal was high (2.6%).

PMID- 19768502
TI  - Mediators of lipid A modification, RNA degradation, and central intermediary
      metabolism facilitate the growth of Legionella pneumophila at low temperatures.
AB  - Legionella pneumophila is an aquatic bacterium that is also the agent of
      Legionnaires' disease pneumonia. Since L. pneumophila is transmitted directly
      from the environment to the lung, it is important to understand how legionellae
      survive at low temperatures. To identify genes that are needed for L. pneumophila
      growth at low temperature, we screened a population of mutagenized legionellae
      for strains that are specifically impaired for growth at 17 degrees C. From the
      7,400 mutants tested, 11 displayed defects ranging from ca. 10-fold to a complete
      inability to grow at the low temperature. PCR and sequence analysis were then
      utilized to identify the genes whose loss had compromised growth. The proteins
      thereby implicated in low-temperature growth included components of the type II
      secretion system (LspE, LspG, LspH), a lipid A biosynthetic enzyme (LpxP), a
      ribonuclease (RNAse R), an RNA helicase (CsdA/DeaD), TCA cycle enzymes (citrate
      synthase), enzymes linked to fatty acid (FadB) or amino acid (aspartate
      aminotransferase) catabolism, and two putative membrane proteins that were, based
      upon their sequences, unlike previously characterized proteins. Given the
      magnitude of their mutant's defect, the aspartate aminotransferase, RNA helicase,
      and one of the putative membrane proteins were the factors most critical for L.
      pneumophila low-temperature growth. Thus, L. pneumophila not only employs some of
      the same processes and factors as other bacteria do in order to survive at low
      temperatures (e.g., LpxP, CsdA), but it also appears to possess novel modes of
      cold adaptation.

PMID- 19768503
TI  - Sequence and phylogenetic analysis of SSU rRNA gene of five microsporidia.
AB  - The complete small subunit rRNA (SSU rRNA) gene sequences of five microsporidia
      including Nosema heliothidis, and four novel microsporidia isolated from Pieris
      rapae, Phyllobrotica armta, Hemerophila atrilineata, and Bombyx mori,
      respectively, were obtained by PCR amplification, cloning, and sequencing. Two
      phylogenetic trees based on SSU rRNA sequences had been constructed by using
      Neighbor-Joining of Phylip software and UPGMA of MEGA4.0 software. The taxonomic
      status of four novel microsporidia was determined by analysis of phylogenetic
      relationship, length, G+C content, identity, and divergence of the SSU rRNA
      sequences. The results showed that the microsporidia isolated from Pieris rapae,
      Phyllobrotica armta, and Hemerophila atrilineata have close phylogenetic
      relationship with the Nosema, while another microsporidium isolated from Bombyx
      mori is closely related to the Endoreticulatus. So, we temporarily classify three
      novel species of microsporidia to genus Nosema, as Nosema sp. PR, Nosema sp. PA,
      Nosema sp. HA. Another is temporarily classified into genus Endoreticulatus, as
      Endoreticulatus sp. Zhenjiang. The result indicated as well that it is feasible
      and valuable to elucidate phylogenetic relationships and taxonomic status of
      microsporidian species by analyzing information from SSU rRNA sequences of
      microsporidia.

PMID- 19768505
TI  - Current opinion on laparoscopic repair of inguinal hernia.

PMID- 19768504
TI  - Impact of neonatal antibiotic treatment on the biodiversity of the murine
      intestinal Lactobacillus community.
AB  - In this study, we investigated the impact of neonatal amoxicillin treatment on
      the development of the murine intestinal Lactobacillus community. Suckling BALB/c
      mice received a daily intragastric gavage of amoxicillin or saline from postnatal
      day 7 (PND 7) to PND 20. Just after the treatment (PND 21) and 5 weeks later (PND
      56), the colon digesta samples were analyzed by Lactobacillus-specific
      quantitative real-time PCR analysis and PCR-denaturing gradient gel
      electrophoresis (DGGE) technique. Real-time PCR results showed that the levels of
      lactobacilli in the treatment group were similar to those in the control at PND
      56. However, in DGGE analysis the number of DGGE bands and Shannon index were
      decreased significantly in comparison with control (P < 0.05). The dominant
      Lactobacillus strain in the murine colon changed from L. johnsonii to L. murinus.
      These results demonstrated that neonatal amoxicillin treatment led to a
      significant impact on the biodiversity of the murine intestinal Lactobacillus
      community within a long-time period.

PMID- 19768506
TI  - SAGES guidelines for the use of laparoscopic ultrasound.

PMID- 19768507
TI  - QTL mapping for frond length and width in Laminaria japonica aresch (Laminarales,
      Phaeophyta) using AFLP and SSR markers.
AB  - In Laminaria japonica Aresch breeding practice, two quantitative traits, frond
      length (FL) and frond width (FW), are the most important phenotypic selection
      index. In order to increase the breeding efficiency by integrating phenotypic
      selection and marker-assisted selection, the first set of QTL controlling the two
      traits were determined in F(2) family using amplified fragment length
      polymorphism (AFLP) and simple sequence repeat (SSR) markers. Two prominent L.
      japonicas inbred lines, one with "broad and thin blade" characteristics and
      another with "long and narrow blade" characteristics, were applied in the
      hybridization to yield the F(2) mapping population with 92 individuals. A total
      of 287 AFLP markers and 11 SSR markers were used to construct a L. japonica
      genetic map. The yielded map was consisted of 28 linkage groups (LG) named LG1 to
      LG28, spanning 1,811.1 cM with an average interval of 6.7 cM and covering the
      82.8% of the estimated genome 2,186.7 cM. While three genome-wide significant QTL
      were detected on LG1 (two QTL) and LG4 for "FL," explaining in total 42.36% of
      the phenotypic variance, two QTL were identified on LG3 and LG5 for the trait
      "FW," accounting for the total of 36.39% of the phenotypic variance. The gene
      action of these QTL was additive and partially dominant. The yielded linkage map
      and the detected QTL can provide a tool for further genetic analysis of two
      traits and be potential for maker-assisted selection in L. japonica breeding.

PMID- 19768508
TI  - Interactive modeling and evaluation of tumor growth.
AB  - This paper addresses the need to quantify tumor growth and detect changes as this
      information is relevant to manage the patient treatment and to aid
      biotechnological efforts to cure cancer (Silva et al. 2008). An interactive tumor
      segmentation technique is used to recover the shape and size of tumors without
      imposing shape constraints. This segmentation algorithm provides good
      convergence, is robust to the initialization conditions, and requires simple and
      intuitive user interactions. A parametric approach to model tumor growth
      analytically is proposed in this paper. The preliminary experimental results are
      encouraging. The segmentation method is shown to be robust and simple to use,
      even in situations where the tumor boundary definition is challenging. Also, the
      experiments indicate that the proposed model potentially can be used to
      extrapolate the available data and help predict the tumor size (assuming
      unconstrained growth). Additionally, the proposed method potentially can provide
      a quantitative reference to compare the tumor shrinkage rate in cancer
      treatments.

PMID- 19768509
TI  - Field attractants for Pachnoda interrupta selected by means of GC-EAD and single
      sensillum screening.
AB  - The sorghum chafer, Pachnoda interrupta Olivier (Coleoptera: Scarabaeidae:
      Cetoniinae), is a key pest on sorghum, Sorghum bicolor (L.) Moench (Poaceae), in
      Ethiopia. At present there is a lack of efficient control methods. Trapping shows
      promise for reduction of the pest population, but would benefit from the
      development of attractive lures. To find attractants that could be used for
      control of P. interrupta, either by mass trapping or by monitoring as part of
      integrated pest management, we screened headspace collections of sorghum and the
      highly attractive weed Abutilon figarianum Webb (Malvaceae) for antennal activity
      using gas chromatograph-coupled electroantennographic detection (GC-EAD).
      Compounds active in GC-EAD were identified by combined gas chromatography and
      mass spectrometry (GC-MS). Field trapping suggested that attraction is governed
      by a few influential compounds, rather than specific odor blends. Synthetic
      sorghum and abutilon odor blends were attractive, but neither blend outperformed
      the previously tested attractants eugenol and methyl salicylate, of which the
      latter also was part of the abutilon blend. The strong influence of single
      compounds led us to search for novel attractive compounds, and to investigate the
      role of individual olfactory receptor neurons (ORNs) in the perception of
      kairomones. We screened the response characteristics of ORNs to 82 putative
      kairomones in single sensillum recordings (SSR), and found a number of key ligand
      candidates for specific classes of ORNs. Out of these key ligand candidates, six
      previously untested compounds were selected for field trapping trials: anethole,
      benzaldehyde, racemic 2,3-butanediol, isoamyl alcohol, methyl benzoate and methyl
      octanoate. The compounds were selected on the basis that they activated different
      classes of ORNs, thus allowing us to test potential kairomones that activate
      large non-overlapping populations of the peripheral olfactory system, while
      avoiding redundant multiple activations of the same ORN type. Field trapping
      results revealed that racemic 2,3-butanediol is a powerful novel attractant for
      P. interrupta.

PMID- 19768510
TI  - Impact of localizing physicians to hospital units on nurse-physician
      communication and agreement on the plan of care.
AB  - BACKGROUND: A significant barrier to communication among patient care providers
      in hospitals is the geographic dispersion of team members. OBJECTIVE: To
      determine whether localizing physicians to specific patient care units improves
      nurse-physician communication and agreement on patients' plans of care. METHODS:
      We conducted structured interviews of a cross-sectional sample of nurses and
      physicians before and after an intervention to localize physicians to specific
      patient care units. Interviews characterized patterns of nurse-physician
      communication and assessed understanding of patients' plans of care. Two
      internists reviewed responses and rated nurse-physician agreement on six aspects
      of the plan of care as none, partial, or complete agreement. RESULTS: Three
      hundred eleven of 342 (91%) and 291 of 294 (99%) patients' nurses and 301 of 342
      (88%) and 285 of 294 (97%) physicians completed the interview during the pre- and
      post-localization periods. Two hundred nine of 285 (73%) patients were localized
      to physicians' designated patient care units in the post-localization period.
      After localization, a higher percentage of patients' nurses and physicians was
      able to correctly identify one another (93% vs. 71%; p < 0.001 and 58% vs. 36%; p
      < 0.001, respectively). Nurses and physicians reported more frequent
      communication after localization (68% vs. 50%; p < 0.001 and 74% vs. 61%; p <
      0.001, respectively). Nurse-physician agreement was significantly improved for
      two aspects of the plan of care: planned tests and anticipated length of stay.
      CONCLUSIONS: Although nurses and physicians were able to identify one another and
      communicated more frequently after localizing physicians to specific patient care
      units, there was little impact on nurse-physician agreement on the plan of care.

PMID- 19768511
TI  - The relationship between the local and systemic inflammatory responses and
      survival in patients undergoing curative surgery for colon and rectal cancers.
AB  - INTRODUCTION: Both local (Klintrup criteria) and systemic (Glasgow Prognostic
      Score, mGPS) inflammatory responses have been reported to be independent
      predictors of cancer-specific survival in colorectal cancer. However, high-grade
      local inflammatory response appears more common in rectal and high mGPS more
      common in colonic tumors. Whether relationships with survival are similar in
      colon and rectal tumors is unclear. The present study assesses the prognostic
      value of local and systemic inflammation in colon and rectal cancers and defines
      3-year survival according to inflammation-based criteria for stage II/III
      disease. METHODS: Two hundred forty colon and 140 rectal cancer patients
      underwent potentially curative surgery between 1997 and 2007. C-reactive protein
      and albumin (mGPS) were measured preoperatively. Routine pathology specimens were
      scored according to Klintrup criteria for peritumoral infiltrate. RESULTS:
      Patients with colon cancers were older (P < 0.05) and had higher T stage (P <
      0.001) and mGPS (P < or = 0.001) compared with rectal cancers. The proportions of
      patients with a high-grade tumor inflammatory cell infiltrate were similar in
      colon and rectal cancers. mGPS and Klintrup criteria were independent predictors
      of cancer survival. The mGPS hazard ratios were 1.56 and 1.76 for the mGPS, and
      the Klintrup hazard ratios were 2.12 and 5.74 for colon and rectum, respectively.
      For stages II and III colorectal cancer, 3-year survival was 91% and 73%,
      respectively. Three-year survival varied between 100% and 68% depending on
      Klintrup score/ mGPS in stage II disease and between 97% and 60% in stage III
      disease. CONCLUSION: Local and systemic inflammatory responses are important
      independent predictors of survival in colon and rectal cancers. These scores
      combined with tumor-node-metastases stage improve the prediction of survival in
      these patients.

PMID- 19768512
TI  - Personalized treatment-the promise of molecular genetics diagnostics.

PMID- 19768513
TI  - Validity of frozen sections for analysis of periprosthetic loosening membranes.
AB  - Clinical findings and blood parameters often are inconclusive in patients with
      periprosthetic joint infections. Among the accepted criteria for diagnosis,
      histologic analysis of debrided tissue can detect infection in most cases but
      does not allow intraoperative decision making. We evaluated the validity of
      intraoperative frozen sections for detection of prosthetic infections. The
      results from frozen and permanent sections of periprosthetic membranes of 64
      consecutive patients who underwent exchange procedures after hip arthroplasty
      were compared using the histopathologic consensus classification of Morawietz et
      al. Blood parameters (erythrocyte sedimentation rate, leukocyte count, C-reactive
      protein) and culture results of preoperatively aspirated joint fluid and
      intraoperative tissue samples were correlated with the histologic results. In 50
      patients (78.1%), agreement was found between the frozen and permanent sections.
      Two patients (3.1%) revealed a discrepancy between the two histologic methods. In
      12 patients (18.8%), a diagnosis was not possible based on the frozen sections
      because the tissue samples were not representative enough for definite
      classification. For the analyzable cases (n = 52), the sensitivity of frozen
      section histologic analysis was 86.6%, specificity 100%, and accuracy 96.2%. Our
      data support a recommendation for use of intraoperative frozen sections for
      diagnosis of septic versus aseptic loosening in revision hip surgery. LEVEL OF
      EVIDENCE: Level II, diagnostic study. See the Guidelines for Authors for a
      complete description of levels of evidence.

PMID- 19768515
TI  - THA with Delta ceramic on ceramic: results of a multicenter investigational
      device exemption trial.
AB  - Although the published studies on the outcomes of total hip arthroplasty (THA)
      performed with currently available ceramic components show high survivorship and
      low bearing wear at midterm followup, concern over ceramic fracture and squeaking
      persist. For these reasons, the use of ceramic is limited. Recently, a new
      alumina matrix composite material (Delta ceramic) with improved material
      properties was developed to address these concerns. We report the early outcomes
      and complications of a prospective, randomized, multicenter trial of 263 patients
      (264 hips) at eight centers, comparing a Delta ceramic-on-ceramic (COC)
      articulation with a Delta ceramic head-crosslinked polyethylene bearing
      combination (COP). There were 177 COC hips and 87 COP hips. Complications were
      reported for all patients, whereas clinical and radiographic results were
      provided for the 233 patients with minimum 2-year followup (average, 31.2 months;
      range, 21-49 months). The Harris hip scores and clinical, radiographic, and
      survivorship outcomes were similar in both groups. There were four (2%) revisions
      in the COC group and two (2%) in the COP group. We encountered three
      intraoperative ceramic liner-related events. In addition, one patient receiving
      the COC underwent revision for chipping of the ceramic liner, and a second had
      ceramic fragmentation on followup radiographs but has not undergone revision.
      These liner related complications remain a concern. No patient reported squeaking
      in either group; this leaves us hopeful the new material will lessen the
      frequency of squeaking. In the short term, the Delta COC articulation provided
      similar functional scores and survivorship and complication rates with the
      ceramic head mated with crosslinked polyethylene. LEVEL OF EVIDENCE: Level I,
      therapeutic study. See Guidelines for Authors for a complete description of
      levels of evidence.

PMID- 19768516
TI  - Reintervention after mobile-bearing Oxford unicompartmental knee arthroplasty.
AB  - BACKGROUND: Medial compartment osteoarthritis is a common disorder that often is
      treated by unicompartmental knee arthroplasty (UKA). Although the Oxford 3
      prosthesis is commonly used based on revision rate and cumulative survival, our
      experience suggests that although there may be adequate implant survival rates,
      we observed a worrisome and undisclosed reintervention rate of nonrevision
      procedures. PURPOSE: We describe the frequency and cause of repeat intervention
      subsequent to implanting this device. METHODS: Between 1998 and 2005, 398
      patients underwent UKA using the Oxford 3 prosthesis. The minimum followup was 12
      months (mean, 43 months; range, 12-102 months). RESULTS: Forty of the 398 (10%)
      patients had 55 (13.8%) repeat anesthetics (reintervention). There were 38
      nonrevision reinterventions. Revision was performed in 15 patients (3.8%), but
      two patients had a second revision (17 revisions or 4.3%). We revised the UKA to
      a second UKA in seven of the 15 cases but two subsequently were rerevised to a
      TKA; eight were revised directly to a TKA. CONCLUSIONS: Although our data confirm
      the reported revision rates for this prosthesis, we observed a substantial
      reintervention rate. Most of the reinterventions are minor and are diagnosed
      frequently and treated arthroscopically. If revision is required, a second UKA
      may be considered and performed successfully in patients with isolated loosening
      of one component. LEVEL OF EVIDENCE: Level II, prognostic study. See Guidelines
      for Authors for a complete description of levels of evidence.

PMID- 19768517
TI  - Leg length and offset measures with a pinless femoral reference array during THA.
AB  - The bony fixation of reference marker arrays used for computer-assisted
      navigation during total hip arthroplasty (THA) theoretically involves the risk of
      fracture, infection, and/or pin loosening. We asked whether intraoperative
      assessment of leg length (LL) and offset (OS) changes would be accurate using a
      novel pinless femoral reference system in conjunction with an imageless
      measurement algorithm based on specific realignment of the relationship between a
      dynamic femoral and pelvis reference array. LL/OS measurements were recorded
      during THA in 17 cadaver specimen hips. Preoperatively and postoperatively,
      specimens were scanned using CT. Linear radiographic LL/OS changes were
      determined by two investigators using visible fiducial landmarks and image
      processing software. We found a high correlation of repeated measurements within
      and between (both 0.95 or greater) the two examiners who did the CT assessments.
      Pinless LL/OS values showed mean differences less than 1 mm and correlations when
      compared with CT measurements.

PMID- 19768518
TI  - Incidental thyroid uptake on F-18 FDG PET/CT: correlation with ultrasonography
      and pathology.
AB  - PURPOSE: To evaluate the usefulness of maximum standard uptake value (max SUV)
      calculated from F-18 fluorodeoxyglucose positron emission tomography/computed
      tomography (FDG PET/CT) examination and findings from ultrasonographic (US)
      examination on incidentally detected thyroid FDG uptake on FDG PET/CT. MATERIALS
      AND METHODS: We collected and reviewed FDG PET/CT images performed at our
      institution from March 2005 to March 2008. This study included 190 subjects with
      increased FDG uptake of thyroid gland who later underwent thyroid US and
      histological examinations. Of these subjects, the uptake pattern on FDG PET/CT
      was classified as either diffuse or focal. The FDG uptake pattern, max SUV, and
      US findings were evaluated and correlated with the histological results. RESULTS:
      In the focal FDG uptake pattern cases (n = 148), the mean max SUV of malignant
      cases was higher than that of benign cases (5.93 +/- 5.35 vs. 3.47 +/- 2.89). Of
      the diffuse FDG uptake cases (n = 42), nodules were detected in 25 subjects
      (59.5%) by US examination. Thyroid nodules were well characterized on US studies,
      and combined findings of suspicious US features or high max SUV of focal FDG
      uptake lesion increased sensitivity, PPV, NPV, and accuracy. CONCLUSIONS: Focal
      uptake pattern and high max SUV may be helpful in differentiating benign and
      malignant nodules on FDG PET/CT. However, US examination provides further
      information, and for lesions with increased FDG uptake of thyroid, US examination
      should be recommended.

PMID- 19768520
TI  - Adenosine receptor agonists affect taurine release from mouse brain stem slices
      in ischemia.
AB  - The release of the inhibitory amino acid taurine is markedly enhanced under
      ischemic conditions in both adult and developing brain stem, together with a
      pronounced increase in the release of the neuromodulator adenosine. We now
      studied the effects of adenosine receptor agonists and antagonists on
      [(3)H]taurine release in the brain stem in normoxia and ischemia, using a
      superfusion system. Under standard conditions, the adenosine A(1) receptor
      agonist N(6)-cyclohexyladenosine (CHA) potentiated basal taurine release in adult
      mice, which response was blocked by the antagonist 8-cyclopentyl-1,3
      dipropylxanthine (DPCPX). CHA and the A(2a) receptor agonist 2-p-(2
      carboxyethyl)phenylamino-5'-N-ethylcarboxaminoadenosinehydrochloride (CGS 21680)
      had no effect on the release in developing mice. In ischemia, CHA depressed both
      basal and K(+)-stimulated taurine release in developing mice in a receptor
      mediated manner, blocked by DPCPX. The A(2a) receptor agonist CGS 21680 was also
      inhibitory. Taurine and adenosine may thus not cooperate in developing mice to
      prevent ischemic neuronal damage. On the other hand, CGS 21680 enhanced taurine
      release in the adult brain stem in ischemia, both basal and K(+)-stimulated
      release being affected. These effects were abolished by the antagonist 3,7
      dimethyl-1-propargylxanthine (DMPX), indicating a receptor-mediated process. In
      this case elevated levels of taurine could be beneficial, protecting against
      hyperexcitation and excitotoxicity.

PMID- 19768519
TI  - The ex vivo production of ammonia predicts L-asparaginase biological activity in
      children with acute lymphoblastic leukemia.
AB  - Patients with acute lymphoblastic leukemia (ALL), who develop antiasparaginase
      antibodies without clinical allergic reactions ("silent inactivation") during L: 
      asparaginase (L: -Asp) treatment, have poor outcomes. Ammonia is produced by
      hydrolysis of asparagine by L: -Asp. We postulated that plasma ammonia level
      might reflect the biological activity of L: -Asp. Five children with ALL treated
      according to the Tokyo Children's Cancer Study Group (TCCSG) protocol were
      enrolled. Plasma ammonia levels were analyzed immediately and 1 h after
      incubation at room temperature and "ex vivo ammonia production" was defined as
      increase in ammonia concentration. Ex vivo ammonia production well correlated
      with L: -Asp activity (r = 0.882, P < 0.01, n = 23). It always exceeded 170
      microg/dL (170-345 microg/dL) in induction therapy. We found 3 patients whose
      ammonia production was negligible during later phases of therapy.
      Antiasparaginase antibody was detected and L: -Asp activity decreased in these
      patients. Ex vivo ammonia production is a surrogate marker of L: -Asp biological
      activity.

PMID- 19768521
TI  - Detection of D-amino acids in purified proteins synthesized in Escherichia coli.
AB  - It has long been believed that amino acids comprising proteins of all living
      organisms are only of the L-configuration, except for Gly. However, peptidyl D
      amino acids were observed in hydrolysates of soluble high molecular weight
      fractions extracted from cells or tissues of various organisms. This strongly
      suggests that significant amounts of D-amino acids are naturally present in usual
      proteins. Thus we analyzed the D-amino acid contents of His-tag-purified beta
      galactosidase and human urocortin, which were synthesized by Escherichia coli
      grown in controlled synthetic media. After acidic hydrolysis for various times at
      110 degrees C, samples were derivatized with 4-fluoro-7-nitro-2, 1, 3
      benzoxadiazole (NBD-F) and separated on a reverse-phase column followed by a
      chiral column into D- and L-enantiomers. The contents of D-enantiomers of Ala,
      Leu, Phe, Val, Asp, and Glu were determined by plotting index D/(D + L) against
      the incubation time for hydrolysis and extrapolating the linear regression line
      to 0 h to eliminate the effect of racemization of amino acids during the
      incubation. Significant contents of D-amino acids were reproducibly detected, the
      D-amino acid profile being specific to an individual protein. This finding
      indicated the likelihood that D-amino acids are in fact present in the purified
      proteins. On the other hand, the D-amino acid contents of proteins were hardly
      influenced by the addition of D- or L-amino acids to the cultivation medium,
      whereas intracellular free D-amino acids sensitively varied according to the
      extracellular conditions. The origin of these D-amino acids detected in proteins
      was discussed.

PMID- 19768522
TI  - Rectal lumen obliteration from stapled hemorrhoidopexy: can it be prevented?
AB  - Stapled hemorrhoidopexy is an operation that is widely used and accepted as a
      standard procedure by many surgery clinics as the postoperative pain is minimal,
      period needed for return to work and social life is short and recurrence rate is
      acceptable. However, stapled hemorrhoidopexy may also result in some major
      complications. An important proportion of these complications (such as
      anastomosis dehiscence, rectovaginal fistula, anorectal stricture and rectal
      obstruction) occur due to the errors of purse string suture technique. In this
      report, we present a case of rectal obstruction following stapled hemorrhoidopexy
      in a 27-year-old female patient with fourth grade hemorrhoidal disease and want
      to draw the attention to the probable ways by which rectal obstruction can occur
      due to this surgical method. The complication that occurred was related to a
      purse string suture that also crossed an internal rectal prolapse. Paying
      attention to the technique of purse string placement during the procedure,
      placing purse string sutures 3-4 cm proximal to the dentate line with intervals
      of 1-1.5 cm, verifying the existence of a lumen before introducing the stapler
      and just including the rectal mucosa will minimize the risk of complications.

PMID- 19768523
TI  - Rectal sleeve advancement for the treatment of persistent rectovaginal fistulas.
AB  - BACKGROUND: Different surgical procedures are available for rectovaginal fistula
      repair. Most of these procedures fail in a substantial number of women,
      especially in those with a persistent fistula after prior attempts at repair. In
      addition, these procedures have a potential risk of dyspareunia and impairment of
      continence. The question is whether rectal sleeve advancement could be a valuable
      option for women with such a persistent rectovaginal fistula. The present study
      was aimed to examine the feasibility of this new procedure. PATIENTS AND METHODS:
      Eight consecutive women (median age 41 years; range 28-53) with a persistent, low
      rectovaginal fistula underwent rectal sleeve advancement, six patients by a
      posterior "Kraske" approach and two patients by an abdominal approach. The
      aetiologies were obstetric trauma (n = 4), prior anal surgery (n = 2) and
      cryptoglandular fistulous disease (n = 2). RESULTS: Five patients had an
      uneventful postoperative course. Three patients encountered recurrent symptoms
      shortly after the procedure. In these three patients an additional transanal
      approach was performed to close the anal opening of the fistulous tract. This
      additional approach was successful in one patient. The median duration of follow
      up was 12 months (range 3-17). The overall healing rate was 75%. None of the
      patients encountered de novo dyspareunia. One patient encountered involuntary
      loss of stool during the night postoperatively. CONCLUSION: Based on these early
      results, rectal sleeve advancement, either by a posterior "Kraske" approach, or
      by an abdominal approach, seems to be a valuable alternative for the treatment of
      persistent rectovaginal fistulas.

PMID- 19768524
TI  - Short-term results of DST EEA 33 stapler and neu@ anoscope for stapled
      haemorrhoidectomy: a prospective study of 1,118 patients from a single centre.
AB  - BACKGROUND: Stapled haemorrhoidectomy has been performed with different
      techniques and staplers. We review our initial experience with the new DST EEA 33
      stapler and neu@ anoscope. METHODS: A review of all patients who underwent
      stapled haemorrhoidectomy using the DST EEA 33 over a 14-month period was
      conducted. Short-term outcomes of bleeding, pain and retention of urine requiring
      admission or strictures requiring surgical intervention were studied. RESULTS:
      There were 1,118 patients operated from August 2007 to October 2008. The median
      age was 46-year-old (20-82 years) and 51% were females. The median operating time
      was 15 min (range 5-45 min), and median follow-up was 7 months (range 3-16
      months). There were 26 patients (2.3%) who were admitted for inability to pass
      urine and 20 required catheterisation. Fifty-two patients (4.6%) were admitted
      for post-operative bleeding. In 32 cases the bleeding stopped spontaneously,
      while 19 patients required adrenaline injection and packing for hemostasis. Only
      one patient required surgical hemostasis. Thirty-three patients (2.9%) were
      admitted for post-operative pain and stayed for a median of 1 day (range 1-4
      days). There were 14 patients (1.2%) who developed anorectal strictures requiring
      surgical intervention. All underwent anoplasty at a median of 3 months post
      operatively (range 2-5 months), with good result. There were no recurrent
      haemorrhoids during follow-up. CONCLUSION: Stapled haemorrhoidectomy using the
      DST EEA 33 stapler is safe. The neu@ anoscope provides good visibility and
      handling, and is a useful tool in this procedure.

PMID- 19768525
TI  - Knowledge, attitudes, and practices of physicians in Tomsk Oblast tuberculosis
      services regarding alcohol use among tuberculosis patients in Tomsk, Russia.
AB  - In recent years, the Russian Federation has seen a dramatic rise in morbidity and
      mortality from tuberculosis (TB), attributed in part to an increase in alcohol
      use disorders (AUDs), which are associated with worse TB treatment outcomes. This
      study describes the knowledge, attitudes and practices of physicians who treat TB
      patients in Tomsk, Russia. We conducted semistructured interviews with 16 TB
      physicians and 1 addiction specialist. Interviews were audiorecorded,
      transcribed, translated and systematically analyzed. We identified four key
      domains: definitions of alcohol use and abuse and physicians' knowledge,
      attitudes and practices regarding these problems. Physicians described patients
      as largely precontemplative and reluctant to seek treatment. Physicians
      recognized their limited knowledge in diagnosing and treating AUDs but expressed
      interest in acquiring these skills. Few options are currently available for
      treatment of AUDs in TB patients in Tomsk. These findings suggest that Tomsk
      physicians are aware of the need to engage AUDs in TB patients but identify a
      knowledge gap that restricts their ability to do so. Training TB physicians to
      use simple screening instruments and deliver evidence-based alcohol interventions
      improves TB outcomes among patients with co-occurring AUDs.

PMID- 19768527
TI  - Study of cosolvent-induced alpha-chymotrypsin fibrillogenesis: does protein
      surface hydrophobicity trigger early stages of aggregation reaction?
AB  - The misfolding of specific proteins is often associated with their assembly into
      fibrillar aggregates, commonly termed amyloid fibrils. Despite the many efforts
      expended to characterize amyloid formation in vitro, there is no deep knowledge
      about the environment (in which aggregation occurs) as well as mechanism of this
      type of protein aggregation. Alpha-chymotrypsin was recently driven toward
      amyloid aggregation by the addition of intermediate concentrations of
      trifluoroethanol. In the present study, approaches such as turbidimetric,
      thermodynamic, intrinsic fluorescence and quenching studies as well as chemical
      modification have been successfully used to elucidate the underlying role of
      hydrophobic interactions (involved in early stages of amyloid formation) in alpha
      chymotrypsin-based experimental system.

PMID- 19768528
TI  - The medical home for children with autism spectrum disorders: parent and
      pediatrician perspectives.
AB  - This qualitative study examines differences between perceptions of parents and
      pediatricians regarding the needs of children with autism spectrum disorders
      (ASDs) and their families within the medical home. Two separate focus groups of
      parents of children with ASDs and pediatricians were conducted. Parents and
      pediatricians identify unmet needs within medical homes of children with ASDs.
      Parents perceived that physicians did not act early upon their concerns about
      development, and that care is less comprehensive, coordinated and family-centered
      than desired. Pediatricians desire to improve services but cite lack of time,
      training and resources as barriers. Medical homes for children with ASDs would
      benefit from better pediatrician ASD education and medical systems that support
      extended visits, care coordination and interdisciplinary collaboration.

PMID- 19768526
TI  - Intrinsically disordered proteins and their environment: effects of strong
      denaturants, temperature, pH, counter ions, membranes, binding partners,
      osmolytes, and macromolecular crowding.
AB  - Intrinsically disordered proteins (IDPs) differ from "normal" ordered proteins at
      several levels, structural, functional and conformational. Amino acid biases
      characteristic for IDPs determine their structural variability and lack of rigid
      well-folded structure. This structural plasticity is necessary for the unique
      functional repertoire of IDPs, which is complementary to the catalytic activities
      of ordered proteins. Amino acid biases also drive atypical responses of IDPs to
      changes in their environment. The conformational behavior of IDPs is
      characterized by the low cooperativity (or the complete lack thereof) of the
      denaturant-induced unfolding, lack of the measurable excess heat absorption
      peak(s) characteristic for the melting of ordered proteins, "turned out" response
      to heat and changes in pH, the ability to gain structure in the presence of
      various counter ions, osmolytes, membranes and binding partners, and by the
      unique response to macromolecular crowding. This review describes some of the
      most characteristic features of the IDP conformational behavior and the unique
      response of IDPs to changes in their environment.

PMID- 19768529
TI  - Antioxidants and sperm DNA damage: a clinical perspective.
AB  - PURPOSE: Infertile men possess substantially more sperm DNA damage than do
      fertile men, damage that may impact negatively on reproductive outcomes. In this
      era of assisted reproductive technologies there is mounting concern regarding the
      safety of utilizing DNA-damaged spermatozoa in this setting. Therefore, it is
      important to identify strategies that may reduce sperm DNA damage. The purpose of
      this review is to discuss the rationale for antioxidant therapy in men with sperm
      DNA damage and to evaluate the data on the efficacy of dietary and in vitro
      antioxidant preparations on sperm DNA damage. METHODS: We reviewed the literature
      on antioxidants and sperm DNA damage. RESULTS: To date, the data suggest that
      dietary antioxidants may be beneficial in reducing sperm DNA damage,
      particularly, in men with high levels of DNA fragmentation. However, the
      mechanism of action of dietary antioxidants has not been established and most of
      the clinical studies are small. A beneficial effect of in vitro antioxidant
      supplements in protecting sperm DNA from exogenous oxidants has been
      demonstrated, however, the effect of these antioxidants in protecting sperm from
      endogenous ROS, gentle sperm processing and cryopreservation has not been
      established.

PMID- 19768530
TI  - Serum anti-Mullerian hormone predicts ovarian response and cycle outcome in IVF
      patients.
AB  - PURPOSE: This prospective study was designed to investigate whether anti
      Mullerian hormone (AMH) levels at basal and ovulation triggering day are
      associated with ovarian response and pregnancy outcome for in vitro fertilization
      (IVF). METHOD: 60 infertility women undergoing IVF were prospectively studied. On
      day 3 of the menstrual cycle (D3), measurements of AMH, inhibin B, FSH, LH, and
      E2 and ultrasound evaluation of antral follicle count (AFC) were performed. Serum
      AMH and inhibin B levels were remeasured on the day of hCG administration (DhCG).
      The outcome measures were the number of retrieved oocytes and clinical pregnancy.
      RESULTS: Number of retrieved oocytes was statistically significant and correlated
      with D3 AMH, AFC, DhCG AMH, DhCG inhibin B, FSH, and age (r=0.885, 0.874, 0.742,
      0.732, -0.521, -0.385, respectively). Statistically significant differences were
      found between pregnant and non-pregnant women regarding D3 AMH and AFC. Multiple
      regression analysis for prediction of pregnancy showed D3 AMH to be a good
      predictor of clinical pregnancy. CONCLUSION: AMH correlates better than age, FSH,
      and inhibin B with the number of retrieved oocytes. Serum basal AMH may offer a
      better prognostic value for clinical pregnancy than other currently available
      markers of IVF outcome in our preliminary study.

PMID- 19768532
TI  - A systematic review of parenting in relation to the development of comorbidities
      and functional impairments in children with attention-deficit/hyperactivity
      disorder (ADHD).
AB  - This review synthesizes recent research evidence regarding the parenting
      characteristics associated with families with children with Attention
      Deficit/Hyperactivity Disorder (ADHD). ADHD is a complex, heterogeneous disorder
      with a range of genetic and environmental factors that contribute to its
      behavioral expression and different developmental trajectories. The current
      review adopts a developmental psychopathology perspective to conceptualize the
      risk and protective factors that might shape the developmental pathways of the
      disorder across different domains. Following from Johnston and Mash's review
      (Johnston and Mash, Clin Child Fam Psychol Rev 4:183-207, 2001), the present
      review systematically examines empirical studies from 2000-2008 that investigate
      parenting variables in relation to the development of children with ADHD, with a
      particular focus on the development of externalizing and internalizing
      comorbidities, as well as functional impairments in academic and social contexts.
      The most recent research evidence uses correlational designs to show that ADHD is
      associated with problematic family functioning, including greater stress within
      the family, higher rates of parental psychopathology and conflicted parent-child
      relationships, which appears to be exacerbated in children with comorbid
      oppositional and conduct problems. However, there is an absence of literature
      that considers the role that parents play in contributing to children's
      development in areas such as academic achievement and peer competence, as well as
      the development of internalizing difficulties. Future research should examine
      family factors that are associated with resilience in children with ADHD, using
      longitudinal designs that reflect the dynamic changes associated with a
      developmental psychopathology framework.

PMID- 19768531
TI  - Vitamins E and D3 attenuate demyelination and potentiate remyelination processes
      of hippocampal formation of rats following local injection of ethidium bromide.
AB  - Cognitive deficits have been observed in patients with multiple sclerosis (MS)
      due to hippocampal insults. Antioxidant vitamins D and E are suggested for
      patients suffering from neurodegenerative diseases like MS, while their
      mechanisms of action are not well understood. Here, we have tried to study the
      effects of these vitamins on demyelination, cell death, and remyelination of rat
      hippocampus following local ethidium bromide (EB) injection. Animals received 100
      mg/kg vitamin E or 5 microg/kg of vitamin D3 for 2, 7, or 28 days. The extent of
      demyelination, myelin staining intensity, and expression of myelin basic protein
      and caspase-3 were investigated using histological and immunoblotting
      verification. Administration of EB alone caused demyelination, cell death, and
      afterward an endogenous repair. Vitamins E and D3 reduced the EB-induced damage
      and increased the endogenous remyelination of hippocampus. Although the anti
      apoptotic effect of these vitamins and protection against demyelination were
      predictable based on their antioxidant effect, our results indicated the positive
      effect of vitamins E and D3 on process of remyelination by endogenous progenitor
      cells and supported their possible therapeutic effects in the context of
      demyelinating diseases like MS.

PMID- 19768533
TI  - Concomitant docetaxel plus gemcitabine versus sequential  docetaxel followed by
      gemcitabine in anthracycline-pretreated  metastatic or locally recurrent
      inoperable breast cancer patients:  a prospective multicentre trial of the
      Central European  Cooperative Oncology Group (CECOG).
AB  - Docetaxel (D) plus gemcitabine (G) is an active combination in anthracycline pre
      treated breast cancer. Impact of sequential administration of these drugs is
      unclear. This trial aimed to compare concomitant DG with sequential D --> G.
      Patients were randomised to eight cycles of gemcitabine 1,000 mg/m2 on days 1 + 8
      plus docetaxel 75 mg/m2 on day 8, or 4 cycles of docetaxel 100 mg/m2 on day 1,
      followed by four cycles of gemcitabine 1,250 mg/m2 on days 1 + 8, in a 21-day
      schedule. Time to progression (TTP) was defined as primary endpoint; secondary
      endpoints were overall response rate (ORR), response duration (RD), overall
      survival (OS) and toxicity. Due to poor recruitment, the trial was terminated
      after 100 of a pre-planned 430 patients. Patient characteristics were well
      balanced. No significant difference was observed in terms of TTP, ORR, RD and OS.
      Grade 3/4 adverse events encompassed leucopoenia (29 vs.68%, P < 0.001),
      neutropoenia (49 vs. 83%, P < 0.001) and febrile neutropoenia (4 vs. 9%, n.s.),
      all favouring D --> G. No difference in efficacy was observed between concomitant
      and sequential treatment. D --> G produced significantly more episodes of
      haematological toxicity due to the administration of docetaxel at 100 mg/m2
      without GCSF support.

PMID- 19768534
TI  - A novel germline CHEK2 deletion truncating the kinase domain identified in a
      French family with high-risk of breast/ovarian cancer.

PMID- 19768535
TI  - Fetal microchimerism in breast from women with and without breast cancer.
AB  - A lasting legacy of a fetus to the mother is a small number of stably persistent
      allogeneic cells; the phenomenon known as fetal microchimerism. Prior studies
      demonstrated that fetal microchimerism in the peripheral blood is associated with
      protection from breast cancer. Whether the same association of fetal
      microchimerism extends to the tissue of interest, the breast, is unknown. Total
      genomic DNA was extracted from frozen normal breast tissue adjacent to invasive
      disease in women with breast cancer. Control DNA was extracted from reduction
      mammoplasty tissues from women with no prior history of any breast cancer. The
      presence of male DNA, presumably from a prior male fetus, was determined with a
      quantitative PCR assay for the Y chromosome gene, DYS14. Proportions of tissues
      harboring fetal microchimerism were compared. Thirty-eight cancer-free breast
      tissues from women with and without a history of breast cancer were evaluable for
      the presence and quantity of fetal microchimerism testing with the DYS14 assay.
      Breast tissue from women free of cancer harbored FMc more frequently than normal
      breast tissue adjacent to invasive disease in women with breast cancer (63 and
      26%, respectively). The odds ratio, corrected for total DNA quantity tested, for
      this protective association of fetal microchimerism against breast cancer was
      0.17 (95% confidence interval 0.04-0.76). Findings indicate that the protective
      association of fetal microchimerism against breast cancer observed previously in
      the peripheral blood is also reflected in breast tissue.

PMID- 19768538
TI  - Toxicity of fungicides to natural bacterial communities in wetland water and
      sediment measured using leucine incorporation and potential denitrification.
AB  - We assessed potential toxicity of fungicides to natural bacterial communities
      from a constructed wetland, located in southern Sweden, and compared the
      sensitivity of two endpoints indicating bacterial activity, leucine
      incorporation, and potential denitrification, in detecting toxicity. The effects
      of eight fungicides (benomyl, carbendazim, carboxin, captan, cycloheximide,
      fenpropimorph, propiconazole, and thiram), two bactericides (bronopol and
      chlortetracycline) as controls, and one reference compound (3,5-dichlorophenol),
      were tested in a water-sediment microcosm set-up. Leucine incorporation was
      measured in both the water and sediment column, while potential denitrification
      was measured for the entire microcosm. The bactericides and the reference
      compound gave sigmoid concentration-response curves for both endpoints in all but
      one case. The fungicides thiram, captan, and benomyl, and to a lesser extent
      fenpropimorph and propiconazole had quantifiable toxic effects on leucine
      incorporation, with EC(50) values ranging from 3 to 70 mg l(-1), while
      carbendazim, carboxin, and cycloheximide had little effect at the investigated
      concentrations. Only thiram and captan inhibited potential denitrification; the
      other fungicides showed no quantifiable effect. A greater toxic effect on leucine
      incorporation was recorded for bacterial communities associated with the water
      column, compared to the sediment column, for all tested compounds. Leucine
      incorporation was the more sensitive method for toxicity assessment of bacterial
      communities, and also allowed for a rapid and simple way of comparing exposure in
      the sediment and water column, making it an attractive standard method for
      community based toxicological assays in aquatic environments.

PMID- 19768537
TI  - Transcriptional regulation of the human ST6GAL2 gene in cerebral cortex and
      neuronal cells.
AB  - The second human beta-galactoside alpha-2,6-sialyltransferase (hST6Gal II)
      differs from hST6Gal I, the first member of ST6Gal family, in substrate
      specificity and tissue expression pattern. While ST6GAL1 gene is expressed in
      almost all human tissues, ST6GAL2 shows a restricted tissue-specific pattern of
      expression, mostly expressed in embryonic and adult brain. In order to understand
      the mechanisms involved in the transcriptional regulation of ST6GAL2, we first
      characterized the transcription start sites (TSS) in SH-SY5Y neuroblastoma cells.
      5' RACE experiments revealed multiple TSS located on three first alternative 5'
      exons, termed EX, EY and EZ, which are unusually close on the genomic sequence
      and are all located more than 42 kbp upstream of the first common coding exon.
      Using Taqman duplex Q-PCR, we showed that the ST6GAL2 transcripts initiated by EX
      or EY are mainly expressed in both brain-related cell lines and human cerebral
      cortex, testifying for the use of a similar transcriptional regulation in vivo.
      Furthermore, we also showed for the first time hST6Gal II protein expression in
      the different lobes of the human cortex. Luciferase reporter assays allowed us to
      define two sequences upstream EX and EY with a high and moderate promoter
      activity, respectively. Bioinformatics analysis and site-directed mutagenesis
      showed that NF-kappaB and NRSF are likely to act as transcriptional repressors,
      whereas neuronal-related development factors Sox5, Puralpha and Olf1, are likely
      to act as transcriptional activators of ST6GAL2. This suggests that ST6GAL2
      transcription could be potentially activated for specific neuronal functions.

PMID- 19768539
TI  - Edaravone protects against apoptotic neuronal cell death and improves cerebral
      function after traumatic brain injury in rats.
AB  - Edaravone is a novel free radical scavenger used clinically in patients with
      acute cerebral infarction; however, it has not been assessed in traumatic brain
      injury (TBI). We investigated the effects of edaravone on cerebral function and
      morphology following TBI. Rats received TBI with a pneumatic controlled injury
      device. Edaravone (3 mg/kg) or physiological saline was administered
      intravenously following TBI. Numbers of 8-OHdG-, 4-HNE-, and ssDNA-positive cells
      around the damaged area after TBI were significantly decreased in the edaravone
      group compared with the saline group (P < 0.01). There was a significant increase
      in neuronal cell number and improvement in cerebral dysfunction after TBI in the
      edaravone group compared with the saline group (P < 0.01). Edaravone
      administration following TBI inhibited free radical-induced neuronal degeneration
      and apoptotic cell death around the damaged area. In summary, edaravone treatment
      improved cerebral dysfunction following TBI, suggesting its potential as an
      effective clinical therapy.

PMID- 19768540
TI  - Ethyl pyruvate inhibits peroxynitrite-induced DNA damage and hydroxyl radical
      generation: implications for neuroprotection.
AB  - Ethyl pyruvate (EP) has recently been reported to afford protection against
      neurodegenerative disorders. However, the mechanism underlying EP-mediated
      neuroprotection remains to be elucidated. Because peroxynitrite has been
      extensively implicated in the pathogenesis of various forms of neurodegenerative
      disorders via its cytotoxic effects, this study was undertaken to investigate
      whether the neuroprotective effect of EP is associated with inhibition of
      peroxynitrite-induced DNA strand breaks, a critical event leading to
      peroxynitrite elicited cytotoxicity. Incubation of phiX-174 plasmid DNA with 3
      morpholinosydnonimine (SIN-1), a peroxynitrite generator, led to the formation of
      both single- and double-stranded DNA breaks in a concentration- and time-
      dependent manner. The presence of EP (0.5-10 mM) was found to significantly
      inhibit SIN-1-induced DNA strand breaks in a concentration-dependent fashion. The
      consumption of oxygen induced by 250 microM SIN-1 was found to be decreased in
      the presence of EP (0.5-10 mM), indicating that EP might affect the auto
      oxidation of SIN-1. It was observed that incubation of the plasmid DNA with
      authentic peroxynitrite caused significant DNA strand breaks, which could also be
      dramatically inhibited by EP (0.5-10 mM). EPR spectroscopy in combination with
      spin-trapping technique using 5,5-dimethylpyrroline-N- oxide (DMPO) as a spin
      trap demonstrated the formation of DMPO-hydroxyl radical adducts (DMPO-OH) from
      authentic peroxynitrite, and that EP at 0.5-10 mM inhibited the adduct signal in
      a concentration-dependent manner. Taken together, these results demonstrate for
      the first time that EP can inhibit peroxynitrite-mediated DNA damage and hydroxyl
      radical generation.

PMID- 19768542
TI  - Assessing and treating co-occurring disorders in adolescents: examining typical
      practice of community-based mental health and substance use treatment providers.
AB  - Co-occurring mental health and substance use disorders in adolescents are common.
      However, limited efforts have been directed at understanding how treatment
      providers in community settings deal with this frequent challenge. In this study,
      treatment providers from both substance use and mental health settings were
      interviewed to examine their common practices regarding the assessment and
      treatment of co-occurring depression and substance use disorders in adolescence.
      About 93% of treatment providers reported treating adolescents with these co
      occurring conditions. However, few providers reported using formal assessment
      practices (23-30%) or treatment protocols for co-occurrence (10%). Providers in
      mental health settings (particularly psychologists) were more likely than those
      in substance use settings to formally assess for depression [Chi2(1, N = 30) =
      3.62, P = .065] but less likely to do so for substance use [Chi2(1, N = 30) =
      9.46, P = .004]. Findings are considered with regard to implications for
      assessment and treatment outcomes in this high-risk population.

PMID- 19768541
TI  - Predictors of referral to Supported Employment among consumers with co-occurring
      mental and substance use disorders.
AB  - Clinical trials demonstrate that Supported Employment is effective in assisting
      persons with severe mental illness in obtaining competitive employment. However,
      little is known about the factors related to consumers' decisions to pursue
      employment, especially for consumers with co-occurring substance and mental
      disorders. This study examines the demographic, socioeconomic and illness
      characteristics of consumers referred for Supported Employment services.
      Consumers were drawn from Integrated Dual Diagnosis Treatment programs in four
      community mental health agencies. Study participants included 113 consumers
      referred for Supported Employment services and 78 randomly selected non-referred
      consumers as the comparison group. Results suggest that consumers who have past
      work experience are more likely to be referred to Supported Employment, while
      consumers who perceive themselves as disabled or who are diagnosed as substance
      dependent are less likely to be referred to Supported Employment. Implications
      for agency practice and future research are discussed.

PMID- 19768543
TI  - Duration of pharmacotherapy with long-acting injectable risperidone in the
      treatment of schizophrenia.
AB  - Although long-acting injectable risperidone (LAIR) has been hypothesized to
      improve medication adherence compared to oral medications, data from real-world
      practice have yet to be presented on time to treatment discontinuation. Records
      of all new prescriptions for antipsychotic medication during the first 2 months
      of FY 2006 for VA patients diagnosed with schizophrenia (N = 11,821) were
      examined and duration of treatment with LAIR and oral antipsychotics were
      calculated for the next 2 years. Multivariable logistic regression was used to
      identify patient characteristics independently associated with receipt of LAIR.
      Proportional hazards models were used to compare the likelihood of discontinuing
      each of the medications as compared to LAIR. Altogether, 2.4% of the 11,821 new
      starts were prescribed LAIR, 44.6% of whom continued therapy for 540-720 days (18
      24 months), less than the 77.1% of those on clozapine, 57.9% on oral conventional
      antipsychotics, 55.0% on olanzapine, and 49.5% on risperidone, but more than the
      27.7% on aripiprazole. After adjusting for potentially confounding factors,
      patients who were initiated on LAIR were more likely to discontinue their
      medication than those who were initiated on oral first- or second-generation
      antipsychotics (SGAs) with the exception ziprasidone and aripiprazole. Less than
      half of patients on LAIR continued treatment for 18 months, a smaller proportion
      than of those started on most oral first- or second-generation antipsychotics,
      suggesting that for many patients with schizophrenia improved adherence from this
      treatment may not be sustained.

PMID- 19768544
TI  - Species-specific pulmonary arterial asymmetry determines species differences in
      regional pulmonary perfusion.
AB  - The functional significance of differences in pulmonary vascular branching and
      diameter asymmetry between the human and quadruped lung has not previously been
      addressed. To evaluate the contribution of branching asymmetry to observable
      species differences in blood flow gradients, computed distributions of blood flow
      were compared in structure-based models of the human and ovine pulmonary
      arteries. The models were derived using a combination of computed tomography and
      a volume-filling algorithm. Pressure, flow, and deformed vessel diameter were
      calculated in both species models using equations representing conservation of
      mass and momentum, and a pressure-diameter relationship. The major difference
      between the human and ovine results was the presence of a large region of "zone
      4" flow and higher mean flows in the central region of the ovine lung compared to
      that in the human. Heterogeneity in tissue perfusion and the contribution of
      gravity were similar in both species models; however, the gravitationally
      directed gradients of perfusion in the human and ovine models were different and
      each consistent with human and quadruped measurements, respectively. The results
      suggest that measured species differences in pulmonary perfusion gradients are
      largely determined by differences in branching asymmetry.

PMID- 19768545
TI  - Surgical and morphological factors that affect internal mechanical loads in soft
      tissues of the transtibial residuum.
AB  - The residual limb of transtibial amputation (TTA) prosthetic users is threatened
      daily by pressure ulcers (PU) and deep tissue injury (DTI) caused mainly by
      sustained mechanical strains and stresses. Several risk factors dominate the
      extent of internal tissue loads in the residuum. In this study, we developed a
      set of three-dimensional finite element (FE) models that were variants of a
      patient-specific FE model, built from magnetic resonance imaging scans. The set
      of FE modes was utilized to assess the impact of the following risk factors on
      the strain/stress distribution in the muscle flap: (i) the tibial length, (ii)
      the tibial bevelment, (iii) a fibular osteophyte, (iv) the mechanical properties
      of the muscle, and (v) scarring in different locations and depths. A total of 12
      nonlinear FE model configurations, representing variations in these factors, were
      built and solved. We present herein calculations of compression, tension and
      shear strains and stresses, von Mises stresses, and strain energy density
      averaged in critical locations in the muscle flap as well as volumes of
      concentration of elevated stresses in these areas. Our results overall show
      higher stresses accumulating in the bone proximity rather than in outlying soft
      tissues. The longer bone configurations spread the loads toward the external
      surfaces of the muscle flap. When shortening the truncated bones from 11.2 to 9.2
      cm, the von Mises stresses at the distal edges of the bones were relieved
      considerably (by up to 80%), which indicates a predicted decreased risk for DTI.
      Decreasing the tibial bevelment mildly, from 52.3 degrees to 37.7 degrees caused
      propagation of internal stresses from the bone proximity toward the more
      superficial soft tissues of the residuum, thereby also theoretically reducing the
      risk for DTI. An osteophyte at the distal fibular end increased the strain and
      stress distributions directly under the fibula but had little effect (<1%) on
      stresses at other sites, e.g., under the tibia. Elevation of muscle stiffness
      (instantaneous shear modulus increase from 8.5 to 16.2 kPa), simulating variation
      between patients, and muscle flap contraction or spasm, showed the most
      substantial effect by an acute rise of the von Mises stresses at the bone
      proximity. The mean von Mises stresses at the bone proximity were approximately
      twofold higher in the contracted/spastic muscle when compared to the flaccid
      muscle. Locating a surgical scar in different sites and depths of the residuum
      had the least influence on the overall loading of the muscle flap (where stresses
      changed by <7%). Pending further validation by epidemiological PU and DTI risk
      factor studies, the conclusions of this study can be incorporated as guidelines
      for TTA surgeons, physical therapists, prosthetists, and the TTA patients
      themselves to minimize the onset of PU and DTI in this population. Additionally,
      the present analyses can be used to guide or focus epidemiological research of PU
      and DTI risk factors in the TTA population.

PMID- 19768546
TI  - The coffee diterpene kahweol induces apoptosis in human leukemia U937 cells
      through down-regulation of Akt phosphorylation and activation of JNK.
AB  - Kahweol, the coffee-specific diterpene, has been reported for its tumor cell
      growth inhibitory activity and anti-carcinogenic activity. The mechanism by which
      kahweol initiates apoptosis remains poorly understood. In the present study, we
      investigated the effect of kahweol on the apoptotic pathway in U937 human
      promonocytic cells. We show that kahweol induces apoptosis in association with
      the activation of caspase 3 and cytochrome c release from the mitochondria to the
      cytosol, as well as down-regulation of anti-apoptotic proteins (Bcl-2, Bcl-xL,
      Mcl-1 and XIAP). Kahweol altered the phosphorylation state of members of the
      MAPKs and Akt. Ectopic expression of Bcl-2 or constitutive active Akt (myr-Akt)
      in U937 cells attenuates kahweol-induced apoptosis. In addition, we have also
      shown that JNK and Akt signal pathway plays a crucial role in kahweol-induced
      apoptosis in U937 cells. Taken together, our results show the activity of kahweol
      to modulate multiple components in apoptotic response of human leukemia cells and
      raise the possibility a novel therapeutic strategy in hematological malignancies.

PMID- 19768550
TI  - Inferior petrosal sinus ACTH and prolactin responses to CRH in ACTH-dependent
      Cushing's syndrome: a single centre experience from the United Kingdom.
AB  - Inferior petrosal sinus sampling (IPSS) of ACTH with CRH stimulation helps
      distinguish pituitary ACTH-dependent Cushing's syndrome from the ectopic ACTH
      syndrome (EAS). The usefulness of the paradoxical response of other pituitary
      hormones including prolactin to CRH remains controversial. Data from 33 IPSS
      procedures carried out at the Walton Centre for Neurology and Neurosurgery in
      Liverpool were analyzed. Patients were selected for this procedure if they had
      been diagnosed with ACTH dependent Cushing's syndrome and the majority had no
      obvious pituitary adenoma on Magnetic Resonance Imaging. Satisfactory
      simultaneous bilateral catheterization was accomplished in 23/33 (success rate
      70%). The diagnostic sensitivity of a basal central/peripheral ACTH ratio >2.0
      and >3 post-CRH was 94%. In two patients with subsequently confirmed EAS the
      maximal central/peripheral ACTH ratio was <2.0 on basal samples and did not
      change following CRH. The maximal central/peripheral prolactin ratio was noted at
      5 min post-CRH, coinciding with the maximal central/peripheral ACTH ratio. The
      intersinus gradient (ISG) of ACTH was paralleled by a consistent ISG of prolactin
      and in 7 out of 9 patients (with successful bilateral IPSS and unilateral
      adenomas) the ISG of prolactin correctly lateralized the microadenoma whereas the
      ISG of ACTH correctly lateralized in 8 out of 9 patients. Neither of the patients
      with EAS achieved a central/peripheral prolactin ratio >2 in the basal state and
      >3 post-CRH. Bilateral catheterization of inferior petrosal sinuses can be
      successful in up to 70% of cases. Prolactin measurements do not have superior
      lateralizing capability compared with ACTH but may be useful in the differential
      diagnosis of pituitary-driven from EAS.

PMID- 19768549
TI  - Physiological responses of the circadian clock to acute light exposure at night.
AB  - Circadian rhythms in physiological, endocrine and metabolic functioning are
      controlled by a neural clock located in the suprachiasmatic nucleus (SCN). This
      structure is endogenously rhythmic and the phase of this rhythm can be reset by
      light information from the eye. A key feature of the SCN is that while it is a
      small structure containing on the order of about 20,000 cells, it is amazingly
      heterogeneous. It is likely that anatomical heterogeneity reflects an underlying
      functional heterogeneity. In this review, we examine the physiological responses
      of cells in the SCN to light stimuli that reset the phase of the circadian clock,
      highlighting where possible the spatial pattern of such responses. Increases in
      intracellular calcium are an important signal in response to light, and this
      increase triggers many biochemical cascades that mediate responses to light.
      Furthermore, only some cells in the SCN are actually endogenously rhythmic, and
      these cells likely do not receive strong direct input from the retina. Therefore,
      this review also considers how light information is conveyed from the
      retinorecipient cells to the endogenously rhythmic cells that track circadian
      phase. A number of neuropeptides, including vasoactive intestinal polypeptide,
      gastrin-releasing peptide and substance P, may be particularly important in
      relaying such signals, but other neurochemicals such as GABA and nitric oxide may
      participate as well. A thorough understanding of the intracellular and
      intercellular responses to light, as well as the spatial arrangements of such
      responses may help identify important pharmacological targets for therapeutic
      interventions to treat sleep and circadian disorders.

PMID- 19768551
TI  - Pediatric emergency consultations: prior mental health service use in suicide
      attempters.
AB  - This study investigated the relationship between presenting complaints and prior
      mental health encounters in youth seen for emergency psychiatric consultation.
      Records of youths aged 9-17 years old receiving a psychiatric consultation in a
      pediatric emergency department from 2002 to 2007 were examined (N=1,900). Youth
      were classified by presenting complaint: suicide attempt, suicidal ideation, and
      behavioral problems. Nearly half of the youth presented with behavior problems,
      and 39% presented with suicidal ideation and/or attempt. Those presenting with
      both suicide attempt and behavior problems were most likely to have made a prior
      suicide attempt. Those presenting with suicide attempt alone were least likely to
      report current mental health treatment, while youth presenting with behavior
      problems alone were the most likely to report current mental health treatment.
      Further research is needed to better understand the role that emergency
      departments play in the course of care and to maximize the opportunity to make
      lasting and effective community-based care connections.

PMID- 19768548
TI  - The impact of genetic research on our understanding of normal cognitive ageing:
      1995 to 2009.
AB  - Identifying the risk factors for individual differences in age-related cognitive
      ability and decline is amongst the greatest challenges facing the healthcare of
      older people. Cognitive impairment caused by "normal ageing" is a major
      contributor towards overall cognitive deficit in the elderly and a process that
      exhibits substantial inter- and intra-individual differences. Both cognitive
      ability and its decline with age are influenced by genetic variation that may act
      independently or via epistasis/gene-environment interaction. Over the past
      fourteen years genetic research has aimed to identify the polymorphisms
      responsible for high cognitive functioning and successful cognitive ageing.
      Unfortunately, during this period a bewildering array of contrasting reports have
      appeared in the literature that have implicated over 50 genes with effect sizes
      ranging from 0.1 to 21%. This review will provide a comprehensive account of the
      studies performed on cognitively healthy individuals, from the first study
      conducted in 1995 to present. Based on current knowledge the strong and weak
      methodologies will be identified and suggestions for future study design will be
      presented.

PMID- 19768552
TI  - Services and supports for individuals with co-occurring disorders and long-term
      homelessness.
AB  - Co-occurring mental health and substance use disorders are highly prevalent among
      individuals experiencing long-term homelessness. This paper describes strategies
      used by 11 projects funded by the Federal Collaborative Initiative to Help End
      Chronic Homelessness (CICH) to serve individuals with co-occurring disorders
      (COD) as they transition from homelessness to permanent-supported housing.
      Findings are based on the observations of clients, program team members, and
      administrators. This paper presents findings organized around three themes:
      characteristics and needs of CICH clients with COD, strategies employed to
      respond to those needs, and challenges associated with implementing an integrated
      approach to COD. Client characteristics include histories of untreated or
      intermittently treated mental health and substance use disorders, often further
      complicated by trauma and chronic illness. Project teams endorsed a variety of
      services and supports such as engagement, stabilization, motivational techniques,
      groups, and trauma-informed interventions as useful for their clients with COD.
      Challenges identified include difficult client behavior, the extended time
      required for change to occur within this population, inadequate staffing and
      community resources, and system barriers. The paper concludes with
      recommendations for further research into the effectiveness of various
      combinations of service strategies for this population in non-traditional
      settings during the earliest stage of recovery, along with a call for overcoming
      workforce and system-level barriers to providing integrated care.

PMID- 19768554
TI  - Human papillomavirus and oropharyngeal cancer: what you need to know in 2009.
AB  - OPINION STATEMENT: Oropharyngeal cancer has demonstrated a steady increase in
      incidence over the past 20 years in contrast to declining numbers of head and
      neck squamous cell carcinoma (HNSCC) overall. Recent evidence has found that high
      risk strains of human papillomavirus (HPV) are the likely cause of the changing
      epidemiology of oropharyngeal cancer. HPV-associated oropharyngeal cancer has a
      molecular, epidemiological, and clinical profile that is distinct from non-HPV
      HNSCC. Clinicians managing oropharyngeal HNSCC need to be aware of differences in
      the HPV HNSCC population which may impact treatment outcomes. Testing of HNSCC
      tumor tissue for HPV using validated and precise techniques should be performed
      when feasible.

PMID- 19768555
TI  - Effect of copper on the activation of the acid phosphatase from the green algae
      Pseudokirchneriella subcapitata.
AB  - The presence of copper in water environment may have detrimental effects on
      aquatic organisms, including algae, where different enzymatic systems can be
      affected. Algae acid phosphatase plays important roles in metabolic processes
      such as decomposition of organic phosphate, autophagic digestive process,
      recycling cellular materials and zygote formation during reproduction. This work
      describes an in vitro activation effect of copper on the acid phosphatase of the
      green algae Pseudokirchneriella subcapitata (formely Selenastrum capricornutum)
      under preincubation condition. Apparent Michaelis constant values of 1.21 and
      0.37 mM, and activation energy values of 26.8 and 13.6 kJ mol(-1) were determined
      in the absence and in the presence of 0.2 mM Cu(2+), respectively. The
      dissociation constant value for Cu(2+) binding to the enzyme was determined to be
      22.04 microM. The decrease of the apparent Michaelis constant (Km) and activation
      energy values in the presence of Cu(2+) correlates well with its activating
      effect on the acid phosphatase activity. This propriety could be used as a
      sensitive bioindicator for copper in environmental samples.

PMID- 19768556
TI  - Advanced glycation end products and antioxidant status in nondiabetic and
      streptozotocin induced diabetic rats: effects of copper treatment.
AB  - The effects of Cu(II) supplementation on glycemic parameters, advanced glycation
      end products (AGEs), antioxidant status (glutathione; GSH and total antioxidant
      capacity; TAOC) and lipid peroxidative damage (thiobarbituric acid-reactive
      substances, TBARS) were investigated in streptozotocin (STZ) induced diabetic
      rats. The study was carried out on Wistar albino rats grouped as control (n =
      10), CuCl(2) treated (n = 9), STZ (n = 10) and STZ,CuCl(2) treated (n = 9). STZ
      was administered intraperitoneally at a single dose of 65 mg/kg and CuCl(2), 4 mg
      copper/kg, subcutaneously, every 2 days for 60 days. At the end of this period,
      glucose(mg/dl), Cu(microg/dl), TBARS(micromol/l), TAOC(mmol/l) were measured in
      plasma, GSH(mg/gHb) in erythrocytes and glycated hemoglobin (GHb)(%) in blood.
      Plasma AGE-peptides(%) were measured by HPLC flow system with spectrofluorimetric
      and spectrophotometric detectors connected on-line. Data were analyzed by the non
      parametric Kruskal-Wallis and Mann-Whitney U test. In the STZ group glucose, GHb
      and AGE-peptide levels were all significantly higher than the control group (P <
      0.01, P < 0.05, and P < 0.01, respectively). CuCl(2) treated group had
      significantly lower glucose but significantly higher GHb, TAOC and TBARS levels
      than the control group (P < 0.05, P < 0.001, P < 0.05 and P < 0.001,
      respectively). STZ,CuCl(2) treated group had significantly higher GHb, TAOC and
      TBARS levels compared with the control group (P < 0.001, P < 0.05 and P < 0.05,
      respectively); but only TAOC level was significantly higher than the STZ group (P
      < 0.01). This experimental study provides evidence that copper intake increases
      total antioxidant capacity in both nondiabetic and diabetic states. However
      despite the potentiated antioxidant defence, lipid peroxidation and glycation
      enhancing effects of CuCl(2) are evident under nondiabetic conditions.

PMID- 19768558
TI  - Application of portable X-ray fluorescence (pXRF) for heavy metal analysis of
      soils in crop fields near abandoned mine sites.
AB  - To get representative soil samples, a sampling method was verified for crop
      fields in the vicinity of abandoned mine sites. Application of appropriate
      sampling or analytical methods is very important as it affects the costs, time,
      and accuracy of the refined investigation of soil contamination. Two-time
      sampling for each crop field was conducted to verify the reproducibility of a
      zigzag method for soil sampling. The soil analysis using a portable X-ray
      fluorescence (pXRF) device was conducted to measure concentrations of metal
      species in soils, and its results were compared to the extracted concentrations
      by the Korean Standard Test (KST) for soils. As a result, the determination
      coefficient (R (2)) of linear regression analysis for data obtained by ex situ
      precise measurement or in situ field screening using pXRF was closely related
      with the ratio of the extracted concentration by KST to interference-free
      detection limits (IFDL) of pXRF (designated as KST/IFDL). As the specific metal
      species had a higher ratio of KST/IFDL, its R (2) was even higher in the field
      screening tests. However, the slopes of linear regression analysis for most metal
      species extracted by aqua-regia were close to 1.0 so that extracted
      concentrations by aqua-regia were similar to the analytical values obtained by
      pXRF, whereas extraction using a weak acid (0.1 M HCl) had different slopes for
      soils contaminated with different ranges of concentrations of metal species.
      Especially Zn showed not only high ratios of KST/IFDL because of aqua regia
      extraction, but also high determination coefficients. Because of its simple,
      rapid, and accurate capacities for metal analysis, the pXRF analysis showed high
      applicability in ex situ precise measurements or in situ field screening of metal
      analysis. In terms of applicability for regulation, especially in situ pXRF field
      screening with the zigzag method could be effectively applied to achieve an
      economical survey by determining hot spots or non-contaminated areas if aqua
      regia was applied as the extracting agent in the KST for soils.

PMID- 19768559
TI  - Novel differential elimination method for determining kinetic coefficients under
      substrate self-inhibition.
AB  - A differential elimination method (DEM) is developed to determine the kinetic
      coefficients for substrate self-inhibition. Finite differentiation of the
      equation eliminates either K(I) or K(S), which enables the equation to be
      linearized so that q, K(S), and K(I) can be estimated without using nonlinear
      least square regression (NLSR). The DEM options that eliminate K(I) or K(S)
      computed the parameter values exactly when the data did not contain any errors.
      If one-point or random errors were not too large, both DEM options worked as well
      as NLSR when data were acquired with geometric intervals for substrate
      concentration. The DEM was more accurate for fitting the data for the smallest
      and largest values of S, but relatively weaker in estimating the observed maximum
      substrate utilization rate, q(max). The estimates for S(max), the concentration
      at which the maximum specific substrate utilization rate is observed, were
      relatively invariant among the methods, even when K(S) and K(I) differed. When
      the intervals were arithmetic (i.e., equal intervals of substrate concentration)
      and the data contained errors, the DEM and NLSR estimated the parameters poorly,
      indicating that collecting data with an arithmetic interval greatly increases the
      risk of poor parameter estimation. Parameter estimates by DEM fit very well
      experimental data from nitrification or photosynthesis, which were taken with
      geometric intervals of substrate concentration or light intensity, but fit poorly
      phenol-degradation data, which were obtained with arithmetic substrate intervals.
      Besides providing a reasonable substitute for NLSR, the DEM also can be used as a
      tool to diagnose the quality of experimental data by comparing its estimates
      between the DEM options, or, more rigorously, to those from NLSR.

PMID- 19768553
TI  - CNS inflammation and macrophage/microglial biology associated with HIV-1
      infection.
AB  - Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous
      system (CNS) can result in neurological dysfunction with devastating consequences
      in a significant proportion of individuals with acquired immune deficiency
      syndrome. HIV-1 does not infect neurons directly but induces damage indirectly
      through the accumulation of activated macrophage/microglia (M/M) cells, some of
      which are infected, that release neurotoxic mediators including both cellular
      activation products and viral proteins. One mechanism for the accumulation of
      activated M/M involves the development in infected individuals of an activated
      peripheral blood monocyte population that traffics through the blood-brain
      barrier, a process that also serves to carry virus into CNS and establish local
      infection. A second mechanism involves the release by infected and activated M/M
      in the CNS of chemotactic mediators that recruit additional monocytes from the
      periphery. These activated M/M, some of which are infected, release a number of
      cytokines and small molecule mediators as well as viral proteins that act on
      bystander cells and in turn activate them, thus amplifying the cascade. These
      viral proteins and cellular products have neurotoxic properties as well, both
      directly and through induction of astrocyte dysfunction, which ultimately lead to
      neuronal injury and death. In patients effectively treated with antiretroviral
      therapy, frank dementia is now uncommon and has been replaced by milder forms of
      neurocognitive impairment, with less frequent and more focal neuropathology. This
      review summarizes key findings that support the critical role and mechanisms of
      monocyte/macrophage activation and inflammation as a major component for HIV-1
      encephalitis or HIV-1 associated dementia.

PMID- 19768557
TI  - Genome-wide analysis of genes encoding FK506-binding proteins in rice.
AB  - The FK506-binding proteins (FKBPs) are a class of peptidyl-prolyl cis/trans
      isomerase enzymes, some of which can also operate as molecular chaperones. FKBPs
      comprise a large ubiquitous family, found in virtually every part of the cell and
      involved in diverse processes from protein folding to stress response. Higher
      plant genomes typically encode about 20 FKBPs, half of these found in the
      chloroplast thylakoid lumen. Several FKBPs in plants are regulators of hormone
      signalling pathways, with important roles in seed germination, plant growth and
      stress response. Some FKBP isoforms exists as homologous duplicates operating in
      finely tuned mechanisms to cope with abiotic stress. In order to understand the
      roles of the plant FKBPs, especially in view of the warming environment, we have
      identified and analysed the gene families encoding these proteins in rice using
      computational approaches. The work has led to identification of all FKBPs from
      the rice genome, including novel high molecular weight forms. The rice FKBP
      family appears to have evolved by duplications of FKBP genes, which may be a
      strategy for increased stress tolerance.

PMID- 19768560
TI  - Brood cell size of Apis mellifera modifies the reproductive behavior of Varroa
      destructor.
AB  - We undertook a field study to determine whether comb cell size affects the
      reproductive behavior of Varroa destructor under natural conditions. We examined
      the effect of brood cell width on the reproductive behavior of V. destructor in
      honey bee colonies, under natural conditions. Drone and worker brood combs were
      sampled from 11 colonies of Apis mellifera. A Pearson correlation test and a
      Tukey test were used to determine whether mite reproduction rate varied with
      brood cell width. Generalized additive model analysis showed that infestation
      rate increased positively and linearly with the width of worker and drone cells.
      The reproduction rate for viable mother mites was 0.96 viable female descendants
      per original invading female. No significant correlation was observed between
      brood cell width and number of offspring of V. destructor. Infertile mother mites
      were more frequent in narrower brood cells.

PMID- 19768561
TI  - The control of eriophyoid mites: state of the art and future challenges.
AB  - The superfamily of the Eriophyoidea is a large and diverse group of mites,
      including a number of species of economic importance, mainly on perennial plants
      in agriculture and forestry. This review focuses on the economic importance and
      pest status of this group of mites, with emphasis on some genera. The available
      acaricide portfolio is reviewed and the influence of EU legislation policy on the
      sustainable control of Eriophyoidea is investigated. Possible generic guidelines
      for sustainable control and resistance management with special reference to the
      European situation are discussed. Recent advances in biological and integrated
      control of eriophyid mite pests and the implementation of these techniques in
      crops are explored. Furthermore, the relevance of studies on behaviour,
      epidemiology and diagnostics in general terms and as a strategic necessity is
      pointed out.

PMID- 19768563
TI  - Green tea consumption and the risk of liver cancer in Japan: the Ohsaki Cohort
      study.
AB  - OBJECTIVES: To investigate the association between green tea consumption and
      liver cancer incidence. METHODS: We prospectively followed 41,761 Japanese adults
      aged 40-79 years, without a history of cancer at the baseline or any missing data
      for green tea consumption frequency. Cox proportional hazards models were used to
      calculate hazard ratios (HR) with 95% confidence intervals (CI), adjusted for
      age, alcohol drinking, smoking, the consumption of coffee, vegetables, dairy
      products, fruit, fish, and soybean. RESULTS: Over 9 years of follow-up, among
      325,947 accrued person-years, the total incidence of liver cancer was 247 cases.
      We found that green tea consumption was inversely associated with the incidence
      of liver cancer. In men, the multivariate-adjusted HRs (95% CIs) for liver cancer
      incidence with different green tea consumption categories were 1.00 (reference)
      for <1 cup/day, 0.83 (0.53-1.30) for 1-2 cups/day, 1.11 (0.73-1.68) for 3-4
      cups/day, and 0.63 (0.41-0.98) for >/=5 cups/day (p for trend = 0.11). The
      corresponding data among women were 1.00 (reference), 0.68 (0.35-1.31), 0.79
      (0.44-1.44), 0.50 (0.27-0.90) (p for trend = 0.04). CONCLUSIONS: Green tea
      consumption is associated with a reduced risk of liver cancer incidence.

PMID- 19768562
TI  - Promoter methylation and the detection of breast cancer.
AB  - Mammographic screening has been shown to reduce breast cancer mortality in women
      over the age of 50 years, and to a lesser extent in younger women. The
      sensitivity of mammography, however, is reduced in some groups of women. There
      remains a need for a minimally invasive, cost-effective procedure that could be
      used along side mammography to improve screening sensitivity. Silencing of tumor
      suppressor genes through promoter hypermethylation is known to be a frequent and
      early event in carcinogenesis. Further, changes in methylation patterns observed
      in tumors are also detectable in the circulation of women with breast cancer.
      This makes these alterations candidate markers for early tumor detection. In this
      paper, we review the current literature on promoter hypermethylation changes and
      breast cancer and discuss issues that remain to be addressed in order for the
      potential of these markers to augment the sensitivity of screening mammography.
      In general, studies in well-defined populations, including appropriate controls
      and larger numbers are needed. Further, focus on the optimization of methods of
      methylation detection in small amounts of DNA is needed.

PMID- 19768564
TI  - Molecular characterization of a putative heat shock protein cognate gene in
      Rhynchosciara americana.
AB  - An hsc70 homologue gene (Rahsc70) of the diptera Rhynchosciara americana was
      isolated and characterized. We were able to determine the mRNA sequence from an
      EST of salivary gland cDNA library, and a Rahsc70 cDNA cassette was used as a
      probe to isolate the genomic region from a genomic library. The mRNA expression
      of this gene parallels the 2B puff expansion, suggesting its involvement in
      protein processing, since this larval period corresponds to a high synthetic
      activity period. During heat shock stress conditions, hsc70 expression decreased.
      In situ hybridization of polytene chromosomes showed that the Rahsc70 gene is
      located near the C3 DNA puff. The cellular localization of Hsc70 protein showed
      this protein in the cytoplasm and in the nucleus.

PMID- 19768565
TI  - Association of macroalbuminuria with oxidized LDL and TGF-beta in type 2 diabetic
      patients: a case-control study.
AB  - The pathogenesis of diabetic nephropathy, mainly characterized by
      macroalbuminuria, is still poorly understood, but it is reported that
      transforming growth factor-beta (TGF-beta) plays a key role. In vitro evidence
      suggests that administration of oxidized LDL (ox-LDL) can lead to upregulation of
      TGF-beta by human glomerular mesangial cells. This study aimed to evaluate the
      association between macroalbuminuria, ox-LDL, and TGF-beta in diabetic patients.
      A total of 77 type 2 diabetic patients with macroalbuminuria (albumin excretion
      rate: AER > or = 300 mg/24 h) and 66 patients with normoalbuminuria (AER < or =
      30 mg/24 h) were recruited. Fasting blood samples were obtained and serum levels
      of ox-LDL and TGF-beta were determined. Ox-LDL and TGF-beta were significantly
      higher in patients with macroalbuminuria than in those with normoalbuminuria
      (98.93 + or - 3.99 vs. 72.45 + or - 2.48 U/l; P < 0.001 and 6.46 + or - 0.74 vs.
      2.49 + or - 0.39 ng/ml; P < 0.001, respectively). In patients with
      macroalbuminuria, there was a significant correlation between Ox-LDL and TGF-beta
      (r = 0.376; P < 0.01). AER was significantly correlated to ox-LDL (r = 0.302; P <
      0.05) and TGF-beta (r = 0.306; P < 0.05) in macroalbuminuric patients. This
      association remained significant after adjustment for potential confounders.
      Adjustment for TGF-beta (ox-LDL), attenuated the association of ox-LDL (TGF-beta)
      with AER. In conclusion, this study demonstrated the association of TGF-beta and
      ox-LDL with albuminuria in macroalbuminuric type 2 diabetic patients, and
      suggested that this relationship is highly mediated through the correlation
      between TGF-beta and ox-LDL.

PMID- 19768566
TI  - A girl of Klippel-Trenaunay Weber syndrome coexistence of recurrent bloody
      vaginal discharge.
AB  - Klippel-Trenaunay Weber syndrome (KTWS) is the coexistence of capillary vascular
      malformations, varicose veins, dilated arteries and arteriovenous fistulas, soft
      tissue and/or bone hypertrophy. We present a girl of KTWS associated with
      hypertrophied left kidney, enlargement in venous structures of the left kidney,
      recurrent bloody vaginal discharge and angiokeratomas. A 6-year-old girl was
      admitted to our department with complaints of recurrent bloody vaginal discharge
      and swelling in the left inguinal region. Physical examination revealed
      hypertrophy of the left lower extremity. Vaginoscopy and cystoscopy revealed
      normal findings. Abdominal ultrasound revealed an enlarged left kidney.
      Enlargement in the venous structures of the hypertrophied left kidney was
      detected by abdominal magnetic resonance imaging, and arteriovenous fistulas were
      revealed by conventional angiography. The patient was diagnosed KTWS. Ophthalmic
      examination was normal. Galactosidase A (GLA) level was found to be at the lower
      limit of the normal range, and mutation was not detected in the GLA gene. In
      conclusion, we have emphasized that the girls with recurrent vaginal discharge
      might be KTWS. Angiokeratoma may be considered as a dermatological finding of
      KTWS. KTWS may also have enlarged kidney and enlargement in venous structures of
      the kidney in hypertrophied side.

PMID- 19768567
TI  - Antioxidant levels of common fruits, vegetables, and juices versus protective
      activity against in vitro ischemia/reperfusion.
AB  - It is well known that antioxidants present in various fruits, vegetables, and
      juices have the potential to protect the urinary bladder from free radical
      damage. What is not well understood, however, is how well antioxidant activities
      detected by chemical methods such as the CUPRAC assay for total antioxidant
      activity (TAA) predict the level of physiological protection available. It is
      hypothesized that the level of antioxidant reactivity found by the CUPRAC assay
      will positively correlate with increased protection in a model of in vitro
      ischemia/reperfusion. To test this hypothesis, the CUPRAC assay was utilized to
      determine the antioxidant reactivity of a series of fruits, vegetables, and
      juices, and the results were compared to the protective ability of selected
      juices in an established in vitro rabbit bladder model of ischemia/reperfusion.
      The results of the CUPRAC test showed that cranberry juice had the highest level
      of antioxidant reactivity, blueberry juice had an intermediate activity, and
      orange juice had the lowest. It was determined, however, that contrary to the
      hypothesis, the orange juice was significantly more potent in protecting the
      bladder against ischemia/reperfusion damage than either blueberry or cranberry
      juice. Thus, it is concluded that chemical tests for TAA do not necessarily
      correlate with their physiological activity.

PMID- 19768568
TI  - Extracting nucleic acids from activated sludge which reflect community population
      diversity.
AB  - Critical to most studies in molecular microbial ecology is the application of
      DNA/RNA extraction methods which can reveal the true level of population
      biodiversity present in samples from the community under investigation. Activated
      sludge communities have been studied extensively using molecular methods, but
      rarely have the nucleic acid isolation methods applied been assessed for their
      ability to achieve this. This study compares eight published RNA and DNA
      extraction protocols and one commercially available DNA isolation kit for their
      capacity to provide high quality nucleic acids that reflect the community
      composition. Each method was assessed on the basis of nucleic acid yield, purity
      and integrity, and the ability to provide PCR amplifiable RNA and DNA from known
      marker populations that varied in their resistance to nucleic acid extraction.
      Only three consistently provided DNA from each of the marker populations known to
      be present in the samples from fluorescence in situ hybridisation analysis. The
      failure of the other methods emphasises the need to validate all DNA/RNA
      extraction protocols. It is recommended that several validated extraction methods
      be used and the extracts pooled to further minimise any risk of bias.

PMID- 19768570
TI  - Prevalence of classical phenylketonuria in mentally retarded individuals in Iran.
AB  - Using Guthrie Biological Inhibition Assay, 4963 mentally retarded individuals
      housed in 31 cities and towns across the country were screened for PKU. The
      average prevalence of classical PKU in the study population was 2.1%, which is
      higher than that reported for most mentally retarded populations in other
      countries prior to the implementation of a nationwide newborn screening programme
      for PKU. The prevalence of PKU in 1814 mentally retarded inmates housed in
      shelters in Tehran was 2.81%, and the prevalence of the disease in 3149 inmates
      sheltered in other cities and towns was 1.68%. It appears that most of the
      difference between the prevalence of PKU in these two populations is due to a
      unique PKU referral pattern in Iran. The high prevalence of PKU in the mentally
      retarded population in Iran could be indicative of a high incidence of the
      disease among Iranian neonates. This in turn appears to be positively influenced
      by both a high frequency of the PKU allele and a high rate of consanguinity in
      the country. Our finding suggests that instead of limited local screening
      programmes in the country, a nationwide screening programme for PKU, especially
      if coupled with screening for congenital hypothyroidism, would be highly cost
      effective and warranted.

PMID- 19768571
TI  - Accessory left atrial diverticulae: contractile properties depicted with 64-slice
      cine-cardiac CT.
AB  - To assess the contractility of accessory left atrial appendages (LAAs) using
      multiphasic cardiac CT. We retrospectively analyzed the presence, location, size
      and contractile properties of accessory LAAs using multiphasic cardiac 64-slice
      CT in 102 consecutive patients (63 males, 39 females, mean age 57). Multiplanar
      reformats were used to create image planes in axial oblique, sagittal oblique and
      coronal oblique planes. For all appendages with an orifice diameter >or= 10 mm,
      axial and sagittal diameters and appendage volumes were recorded in atrial
      diastole and systole. Regression analysis was performed to assess which imaging
      appearances best predicted accessory appendage contractility. Twenty-three (23%)
      patients demonstrated an accessory LAA, all identified along the anterior LA
      wall. Dimensions for axial oblique (AOD) and sagittal oblique (SOD) diameters and
      sagittal oblique length (SOL) were 6.3-19, 3.4-20 and 5-21 mm, respectively. All
      appendages (>or=10 mm) demonstrated significant contraction during atrial systole
      (greatest diameter reduction was AOD [3.8 mm, 27%]). Significant correlations
      were noted between AOD-contraction and AOD (R = 0.57, P < 0.05) and SOD
      contraction and AOD, SOD and SOL (R = 0.6, P < 0.05). Mean diverticulum volume in
      atrial diastole was 468.4 +/- 493 mm(3) and in systole was 171.2 +/- 122 mm(3),
      indicating a mean change in volume of 297.2 +/- 390 mm(3), P < 0.0001. Stepwise
      multiple regression analysis revealed SOL to be the strongest independent
      predictor of appendage contractility (R(2) = 0.86, P < 0.0001) followed by SOD
      (R(2) = 0.91, P < 0.0001). Accessory LAAs show significant contractile properties
      on cardiac CT. Those accessory LAAs with a large sagittal height or depth should
      be evaluated for contractile properties, and if present should be examined for
      ectopic activity during electrophysiological studies.

PMID- 19768572
TI  - Coronary calcium mass scores measured by identical 64-slice MDCT scanners are
      comparable: a cardiac phantom study.
AB  - To assess whether absolute mass scores are comparable or differ between identical
      64-slice MDCT scanners of the same manufacturer and to compare absolute mass
      scores to the physical mass and between scan modes using a calcified phantom. A
      non-moving anthropomorphic phantom with nine calcifications of three sizes and
      three densities was scanned 30 times on three 64-slice MDCT scanners of
      manufacturer A and on three 64-slice MDCT scanners of manufacturer B in both
      sequential and spiral scan mode. The mean mass scores and mass score
      variabilities of seven calcifications were determined for all scanners; two non
      detectable calcifications were omitted. It was analyzed whether identical
      scanners yielded similar or significantly different mass scores. Furthermore mass
      scores were compared to the physical mass and mass scores were compared between
      scan modes. The mass score calibration factor was determined for all scanners.
      Mass scores obtained on identical scanners were similar for almost all
      calcifications. Overall, mass score differences between the scanners were small
      ranging from 1.5 to 3.4% for the total mass scores, and most differences between
      scanners were observed for high density calcifications. Mass scores were
      significantly different from the physical mass for almost all calcifications and
      all scanners. In sequential mode the total physical mass (167.8 mg) was
      significantly overestimated (+2.3%) for 4 out of 6 scanners. In spiral mode a
      significant overestimation (+2.5%) was found for system B and a significant
      underestimation (-1.8%) for two scanners of system A. Mass scores were dependent
      on the scan mode, for manufacturer A scores were higher in sequential mode and
      for manufacturer B in spiral mode. For system A using spiral scan mode no
      differences were found between identical scanners, whereas a few differences were
      found using sequential mode. For system B the scan mode did not affect the number
      of different mass scores between identical scanners. Mass scores obtained in the
      same scan mode are comparable between identical 64-slice CT scanners and
      identical 64-slice CT scanners on different sites can be used in follow-up
      studies. Furthermore, for all systems significant differences were found between
      mass scores and the physical calcium mass; however, the differences were
      relatively small and consistent.

PMID- 19768573
TI  - (123)I-BMIPP and (99m)Tc-TF discordance on myocardial scintigraphy and it's
      correlation with functional recovery following acute myocardial infarction: role
      of conventional echocardiography.
AB  - (123)I-beta-methyl-iodophenyl pentadecanoic acid (BMIPP) and (99m)Tc-Tetrofosmin
      (TF) mismatch designated as stunned myocardium having both systolic and diastolic
      components. The degree of mismatch might reflect subsequent functional
      improvement, and this study was designed to unravel the impact of mismatched
      defect score (MMDS) on recovery of both systolic and diastolic function following
      acute myocardial infarction (AMI). Forty patients with recent AMI were recruited,
      and all of them underwent emergency percutaneous coronary intervention.
      Echocardiography and BMIPP and TF cardiac scintigraphy were performed on 7 +/- 3
      days of admission. Follow up echocardiography was performed after 3 months. MMDS
      were compared with the systolic [ejection fraction (EF) and wall motion score
      index (WMSI)] and diastolic [peak velocity of early diastolic filling of mitral
      inflow/peak early diastolic velocity of the mitral annulus(E/E') and left atrial
      volume index(LAVI)] parameters. BMIPP defect score was significantly higher than
      the TF defect score and there was a strong positive correlation between them (r =
      0.90, P < 0.00001). Thirty-two (80%) patients showed mismatched defect and rest
      8(20%) showed matched defect. Of 32 patients 24(75%), 22(69%), 19(59%), and
      20(62.5%) showed improved EF, WMSI, E/E' and LAVI respectively. Conversely out of
      8 only 2(25%), 1(12.5%), and 2(25%) patients showed improvement of EF, WMSI and
      LAVI, respectively. E/E' was not improved in patients with matched defect. MMDS
      were significantly correlated with the improvement of EF (r = -0.46, P = 0.002),
      WMSI (r = 0.41, P = 0.007), E/E' (r = 0.56, P < 0.0002), and LAVI (r = 0.44, P =
      0.004). Mismatched defect score could predict the approximate amount of viable
      dysfunctional myocardium, and the degree of mismatch showed a significant
      correlation with the improvement of both systolic and diastolic function.

PMID- 19768574
TI  - Seroepidemiological survey of paracoccidioidomycosis infection among urban and
      rural dogs from Uberaba, Minas Gerais, Brazil.
AB  - There is some evidence that dogs can be naturally infected by Paracoccidioides
      brasiliensis in endemic areas of paracoccidioidomycosis. In order to evaluate
      canine infection with this fungus, a survey with 149 urban and 126 rural dogs was
      carried out using ELISA and intradermal tests with the gp43 antigen of P.
      brasiliensis in Uberaba, Minas Gerais state of Brazil. Forty-one out of 149 urban
      dogs were euthanatized and had their lungs, liver and spleen removed. One slice
      from each viscera was processed for histopathological examination and the
      remaining was homogenized and then cultivated on mycobiotic agar at room
      temperature and Fava-Netto medium at 35 degrees C and observed for 12 weeks. Of
      urban dogs, 75 (50.3%) were small adult females, 56 (36%) were strays, while 93
      (64%) had been donated to the municipal zoonosis control center. Nine (6.2%) had
      a positive intradermal test without statistical differences regarding gender,
      race, nutritional status or origin. No colonies with microscopic or morphology
      appearances resembling P. brasiliensis were isolated, nor granulomatous process
      or fungal structures were observed from histopathological examination. Eighty
      (53.6%) of the urban dogs presented seroreactivity, without statistical
      differences regarding gender, race, nutritional state, origin, or positive
      intradermal test. Of 126 rural dogs, 102 (80.5%) presented antibodies against
      gp43 antigen, and this was statistically significant in relation to the
      reactivity detected in urban dogs (P = 0.0001). Thus, dogs are commonly infected
      with P. brasiliensis, but they probably present natural resistance to develop
      paracoccidioidomycosis.

PMID- 19768575
TI  - TIM-3 as a new therapeutic target in systemic lupus erythematosus.
AB  - T-cell immunoglobulin- and mucin-domain-containing molecule-3 (TIM-3) was the
      first surface molecule that specifically identifies Th1 cells in both mice and
      human. Recently, identification of Galectin-9 as a ligand for TIM-3 has
      established the TIM-3-Galectin-9 pathway as an important regulator of Th1
      immunity and tolerance induction. Many previous studies have demonstrated that
      TIM-3 influences chronic autoimmune diseases, such as multiple sclerosis and
      rheumatoid arthritis. In addition, association of TIM-3 polymorphisms with
      susceptibility to several autoimmune diseases has been identified. Recent work
      has explored the role of TIM-3 in systemic lupus erythematosus (SLE), and their
      results indicate that TIM-3 may represent a novel target for the treatment of
      SLE. In this review, we will discuss the TIM-3 pathway and the therapeutic
      potential of modulating the pathway in SLE.

PMID- 19768576
TI  - Expression and SNP association analysis of porcine FBXL4 gene.
AB  - As a kind of E3 ligase, the product of FBXL4 gene belongs to a member of FBLs
      which is the biggest eukaryotic subfamily of F-BOX proteins, it can recognize
      some substrate through particular protein-protein interaction domains. To
      investigate its functions, the polymorphism and association analysis was
      analyzed. The partial cDNA of porcine FBXL4 with 2384 bp long was first cloned;
      the deduced protein comprises a conserved F-BOX domain at position from the 277th
      to 332nd amino acid. The phylogenetic tree indicated porcine FBXL4 has the
      closest genetic relationship with bovine FBXL4 than other selected animal
      species. Ten tissue expression level of porcine FBXL4 mRNA fluctuated remarkably
      in a large range by quantitative RT-PCR analysis. For two identified SNPs, the
      genotyping analysis of Tail showed TT genotype owned dominance in introduced
      Landrace pig and miniature Guizhou and Wuzhishan breeds, but CC genotype was more
      than two other genotypes in miniature Laiwu breed. While in another genotyping
      analysis of BsaJI, CC genotype was obviously more than other genotypes in two
      kinds of Chinese miniature pig breeds and introduced Landrace pig breeds.
      Furthermore, the association analysis with immune traits and blood parameters
      revealed that SNP Tail was significantly associated with the lymphocyte
      percentage (P = 0.0166) and the antibody levels for pseudorabies virus
      vaccination (P = 0.0001) of neonate piglets at 0 day. Meanwhile, SNP BsaJI was
      significantly associated with lymphocyte percentage of individuals at 32 days (P
      = 0.0351), neutrophil percentage (P = 0.0005), the absolute lymphocyte count (P =
      0.0458), and the mixed cells (P = 0.0010) of neonate piglets at 0 day.

PMID- 19768577
TI  - Multi-variety bone bank in China.
AB  - This is a descriptive report of the establishment and operation of a Chinese bone
      bank, though not a typical one. While being engaged in collection, processing and
      storage of allogeneic tissues, the bone bank to which the author belongs
      concurrently develops and produces new, non-human derived, graft materials. Among
      others is reconstituted bone xenograft (RBX) which possesses strong
      osteoinductive capability without evoking immune rejection. Hence, its
      appellation "multi-variety bone bank," which was established by Dr. Hu Yunyu in
      1990, the first of its kind in China. There are several salient features
      discriminating this bone bank from others. At this hospital-based non-profit
      institution, allograft hemi-joints are freshly prepared and distributed deep
      frozen, instead of being freeze-dried on an industrialized basis for convenient
      transportation. The former has much more superior biological and mechanical
      properties as compared with the latter. However, allogeneic tissues are sometimes
      in short supply due to limited number of donors and the risk of some potential
      donors carrying viruses such as human immunodeficiency virus (HIV), hepatitis B
      virus (HBV), or hepatitis C virus (HCV). New graft materials, including
      reconstituted bone xenograft (RBX), were developed that serve as a supplement to
      allografts. RBX has been successfully used in clinical practice for the
      management of old fractures, nonunions and bone defects, most notably of
      contaminated, infected open fractures and osteomyelitis with the use of anti
      infective reconstituted bone xenograft (ARBX). Additionally the multi-variety
      bone bank serves as a training base for educating professional personnel and
      researchers (postgraduates) in theories and technologies of tissue banking. Up to
      now, eighteen special technical staff members and approximately sixty senior
      researchers have been trained at this institution.

PMID- 19768578
TI  - Mutation analysis of the APC gene in Taiwanese FAP families: low incidence of APC
      germline mutation in a distinct subgroup of FAP families.
AB  - Familial adenomatous polyposis (FAP) is an autosomal-dominant disease caused by
      germline mutations in the adenomatous polyposis coli (APC) gene. The affected
      individuals develop colorectal polyposis and show various extra-colonic
      manifestations. In this study, we aimed to investigate the genetic and clinical
      characteristics of FAP in Taiwanese families and analyze the genotype-phenotype
      correlations. Blood samples were obtained from 66 FAP patients registered in the
      hereditary colorectal cancer database. Then, germline mutations in the APC genes
      of these 66 polyposis patients from 47 unrelated FAP families were analyzed. The
      germline-mutation-negative cases were analyzed by performing multiplex ligation
      dependent probe amplification (MLPA) and single-strand conformation polymorphism
      (SSCP) analysis of the MUTYH gene. Among the analyzed families, 79% (37/47) of
      the families showed 28 APC mutations, including 19 frameshift mutations, 4
      nonsense mutations, 3 genomic deletion mutations, 1 missense mutation, and 1
      splice-site mutation. In addition, we identified 15 novel mutations in 32%
      (15/47) of the families. The cases in which APC mutations were not identified
      showed significantly lower incidence of profuse polyposis (P = 0.034) and
      gastroduodenal polyps (P = 0.027). Furthermore, FAP families in which some
      affected individuals had less than 100 polyps showed significant association with
      low incidence of APC germline mutations (P = 0.002). We have added the APC
      germline-mutation data for Taiwanese FAP patients and indicated the presence of
      an FAP subgroup comprising affected individuals with nonadenomatous polyps or
      less than 100 adenomatous polyps; this form of FAP is less frequently caused by
      germline mutations of the APC gene.

PMID- 19768580
TI  - Patenting and licensing of university research: promoting innovation or
      undermining academic values?
AB  - Since the 1980s in the US and the 1990s in Europe, patenting and licensing
      activities by universities have massively increased. This is strongly encouraged
      by governments throughout the Western world. Many regard academic patenting as
      essential to achieve 'knowledge transfer' from academia to industry. This trend
      has far-reaching consequences for access to the fruits of academic research and
      so the question arises whether the current policies are indeed promoting
      innovation or whether they are instead a symptom of a pro-intellectual property
      (IP) culture which is blind to adverse effects. Addressing this question requires
      both empirical analysis (how real is the link between academic patenting and
      licensing and 'development' of academic research by industry?) and normative
      assessment (which justifications are given for the current policies and to what
      extent do they threaten important academic values?). After illustrating the major
      rise of academic patenting and licensing in the US and Europe and commenting on
      the increasing trend of 'upstream' patenting and the focus on exclusive as
      opposed to non-exclusive licences, this paper will discuss five negative effects
      of these trends. Subsequently, the question as to why policymakers seem to ignore
      these adverse effects will be addressed. Finally, a number of proposals for
      improving university policies will be made.

PMID- 19768579
TI  - Effects of the anesthetic agent propofol on neural populations.
AB  - The neuronal mechanisms of general anesthesia are still poorly understood.
      Besides several characteristic features of anesthesia observed in experiments, a
      prominent effect is the bi-phasic change of power in the observed
      electroencephalogram (EEG), i.e. the initial increase and subsequent decrease of
      the EEG-power in several frequency bands while increasing the concentration of
      the anaesthetic agent. The present work aims to derive analytical conditions for
      this bi-phasic spectral behavior by the study of a neural population model. This
      model describes mathematically the effective membrane potential and involves
      excitatory and inhibitory synapses, excitatory and inhibitory cells, nonlocal
      spatial interactions and a finite axonal conduction speed. The work derives
      conditions for synaptic time constants based on experimental results and gives
      conditions on the resting state stability. Further the power spectrum of Local
      Field Potentials and EEG generated by the neural activity is derived analytically
      and allow for the detailed study of bi-spectral power changes. We find bi-phasic
      power changes both in monostable and bistable system regime, affirming the
      omnipresence of bi-spectral power changes in anesthesia. Further the work gives
      conditions for the strong increase of power in the delta-frequency band for large
      propofol concentrations as observed in experiments.

PMID- 19768581
TI  - (1)H, (13)C, and (15)N NMR assignments of StnII-R29Q, a defective lipid binding
      mutant of the sea anemone actinoporin Sticholysin II.
AB  - Several studies have been made to characterize the molecular properties and
      activity of Sticholysin II (StnII), a 175 amino acid protein secreted by the sea
      anemone Stichodactyla helianthus. In particular, the biochemical characterization
      of different mutants of this protein have been shown to be essential for the
      rational understanding of its activity. Here we report the nearly complete NMR
      (15)N, (13)C and (1)H chemical shift assignments, at pH 4.0 and 25 degrees C, of
      a less hemolytic and defective lipid binding mutant of StnII, the R29Q variant
      (BMRB no 16362).

PMID- 19768582
TI  - PEST sequences mediate heat shock factor 2 turnover by interacting with the Cul3
      subunit of the Cul3-RING ubiquitin ligase.
AB  - Cullin-RING ubiquitin ligases promote the polyubiquitination and degradation of
      many important cellular proteins, which previous studies indicated can be
      targeted for degradation via interaction with BTB domain-containing subunits of
      this E3 ligase complex. PEST domains are known to promote the degradation of
      proteins that contain them. However, the molecular mechanism by which PEST
      sequences promote degradation of these proteins is not understood. Here we show
      that the PEST sequences of a short-lived protein called HSF2 interact with
      Cullin3, a subunit of a Cullin-RING E3 ubiquitin ligase, and that this
      interaction mediates the Cul3-dependent ubiquitination and degradation of HSF2.
      These results indicate how, at the molecular level, PEST sequences can promote
      the proteolysis of proteins that contain them. They also expand understanding of
      the mechanisms by which substrates can be recruited to Cullin-RING E3 ubiquitin
      ligases to include interactions between PEST sequences and Cul3.

PMID- 19768583
TI  - Spontaneous pyopneumothorax in patients treated with mTOR inhibitors for
      subpleural pulmonary metastases.
AB  - Spontaneous pyopneumothorax is a very rare occurrence, even in cancer treated
      patients. Here we present two consecutive cases of spontaneous pyopneumothorax
      that occurred early after initiation of mTOR inhibitors for the treatment of
      renal cell carcinoma with subpleural pulmonary metastasis. In these two cases,
      necrosis and excavation of lung metastasis were observed, suggesting their
      involvement in the pathogenic mechanism of pyopneumothorax. This report extends
      the available experience of the pulmonary side effects of these novel targeted
      therapies.

PMID- 19768584
TI  - SNPs: impact on gene function and phenotype.
AB  - Single nucleotide polymorphism (SNP) is the simplest form of DNA variation among
      individuals. These simple changes can be of transition or transversion type and
      they occur throughout the genome at a frequency of about one in 1,000 bp. They
      may be responsible for the diversity among individuals, genome evolution, the
      most common familial traits such as curly hair, interindividual differences in
      drug response, and complex and common diseases such as diabetes, obesity,
      hypertension, and psychiatric disorders. SNPs may change the encoded amino acids
      (nonsynonymous) or can be silent (synonymous) or simply occur in the noncoding
      regions. They may influence promoter activity (gene expression), messenger RNA
      (mRNA) conformation (stability), and subcellular localization of mRNAs and/or
      proteins and hence may produce disease. Therefore, identification of numerous
      variations in genes and analysis of their effects may lead to a better
      understanding of their impact on gene function and health of an individual. This
      improved knowledge may provide a starting point for the development of new,
      useful SNP markers for medical testing and a safer individualized medication to
      treat the most common devastating disorders. This will revolutionize the medical
      field in the future. To illustrate the effect of SNPs on gene function and
      phenotype, this minireview focuses on evidences revealing the impact of SNPs on
      the development and progression of three human eye disorders (Norrie disease,
      familial exudative vitreoretinopathy, and retinopathy of prematurity) that have
      overlapping clinical manifestations.

PMID- 19768585
TI  - Silent (synonymous) SNPs: should we care about them?
AB  - One of the surprising findings of the Human Genome Project was that single
      nucleotide polymorphisms (SNPs), which, by definition, have a minor allele
      frequency greater than 1%, occur at higher rates than previously suspected. When
      occurring in the gene coding regions, SNPs can be synonymous (i.e., not causing a
      change in the amino acid) or nonsynonymous (when the amino acid is altered). It
      has long been assumed that synonymous SNPs are inconsequential, as the primary
      sequence of the protein is retained. A number of studies have questioned this
      assumption over the last decade, showing that synonymous mutations are also under
      evolutionary pressure and they can be implicated in disease. More importantly,
      several of the mechanisms by which synonymous mutations alter the structure,
      function, and expression level of proteins are now being elucidated. Studies have
      demonstrated that synonymous polymorphisms can affect messenger RNA splicing,
      stability, and structure as well as protein folding. These changes can have a
      significant effect on the function of proteins, change cellular response to
      therapeutic targets, and often explain the different responses of individual
      patients to a certain medication.

PMID- 19768586
TI  - SNP databases.
AB  - Researchers interested in obtaining detailed information on SNPs now work in a
      golden age of online database availability: never has so much data and such a
      wealth of information been freely accessible for such a substantial proportion of
      the 18 million single nucleotide polymorphism (SNP) loci currently characterized
      in the human genome. This chapter describes the major SNP databases available for
      human genetics studies. Tools and strategies are outlined that can help
      researchers properly formulate a database query to be able to access the most
      appropriate information needed for their research aims, including medical or
      population genetics analysis--an approach that is getting increased attention
      given the expanding scale of online SNP data.

PMID- 19768587
TI  - Mining SNPs from DNA sequence data; computational approaches to SNP discovery and
      analysis.
AB  - Single nucleotide polymorphisms (SNPs) are the most abundant form of genetic
      variation and are the basis for most molecular markers. Before these SNPs can be
      used for direct sequence-based SNP detection or in a derived SNP assay, they need
      to be identified. For those regions or species where no validated SNPs are
      available in the public databases, a good alternative is to mine them from DNA
      sequences. The alignment of multiple sequence fragments originating from
      different genotypes representing the same region on the genome will allow for the
      discovery of sequence variants. The corresponding nucleotide mismatches are
      likely to be SNPs or insertions/deletions. A large amount of sequence data to be
      mined is present in the public databases (both expressed sequence tags and
      genomic sequences) and is free to use without having to do large-scale sequencing
      oneself. However, with the appearance of the next-generation sequencing machines
      (Roche GS/454, Illumina GA/Solexa, SOLiD), high-throughput sequencing is becoming
      widely available. This will allow for the sequencing of polymorphic genotypes on
      specific target areas and consequent SNP identification. In this paper we discuss
      the bioinformatics tools required to analyze DNA sequence data for SNP mining. A
      general approach for the consecutive steps in the mining process is described and
      commonly used SNP discovery pipelines are presented.

PMID- 19768588
TI  - Next-generation sequencing methods: impact of sequencing accuracy on SNP
      discovery.
AB  - The advent of next-generation sequencing technologies has spurred remarkable
      progress in the field of genomics. Whereas traditional Sanger sequencing has
      yielded the first complete human genome sequence, next-generation methods have
      been able to resequence several human genomes. In this manner, next-generation
      approaches have powerful capabilities for understanding human variation. The
      throughput for these approaches is often measured in billions of base pairs per
      run, astounding numbers when compared with the millions of base pairs per day
      generated by automated capillary DNA sequencers. However, unlike traditional
      Sanger dideoxy sequencing, these methods have lower accuracy and shorter read
      lengths than the dideoxy gold standard. Are these limitations offset by the
      higher throughputs? An in-depth look at the single read and composite accuracy of
      these methods is presented. The stringent requirements for single nucleotide
      polymorphism (SNP) discovery utilizing these approaches is discussed along with a
      review of studies that have successfully employed next-generation sequencing
      methods for large-scale SNP discovery. Ultimately, the application of these ultra
      high-throughput sequencing methods for SNP discovery will open up new horizons
      for understanding human genomic variation.

PMID- 19768589
TI  - Scanning probe and nanopore DNA sequencing: core techniques and possibilities.
AB  - We provide an overview of the current state of research towards DNA sequencing
      using nanopore and scanning probe techniques. Additionally, we provide methods
      for the creation of two key experimental platforms for studies relating to
      nanopore and scanning probe DNA studies: a synthetic nanopore apparatus and an
      atomically flat conductive substrate with stretched DNA molecules.

PMID- 19768590
TI  - Pyrosequencing for SNP genotyping.
AB  - Pyrosequencing is a real-time DNA sequencing method. It is based on the
      transformation of pyrophosphates, released during DNA elongation by DNA
      polymerase, into measurable light. During DNA elongation, a single pyrophosphate
      molecule is released following incorporation of a single nucleotide. In the
      pyrosequencing reaction, released pyrophosphates are then rapidly converted by
      sulfurylase to adenosine triphosphate, which in turn is utilized by luciferase to
      produce light. Within standardized conditions, this reaction is accomplished in a
      few milliseconds and the light produced can be registered with a CCD camera.
      Therefore, it becomes possible to quantitatively measure the nucleotides
      incorporated. This approach has been automated in different platforms and can be
      used for a wide variety of applications, such as single-nucleotide polymorphism
      (SNP) genotyping, DNA sequencing, loss of heterozygosity analysis, and CpG
      methylation studies. Here we describe the entire process, focusing our attention
      on SNP genotyping, and giving examples of some other applications.

PMID- 19768591
TI  - Single nucleotide polymorphism screening with denaturing gradient gel
      electrophoresis.
AB  - Denaturing gradient gel electrophoresis (DGGE) is a powerful technique for
      identifying DNA sequence-based differences. The method relies on the fact that
      double-stranded DNA molecules have unique denaturation rates that are based upon
      the specific nucleotide composition of the DNA sequence(s). While DGGE is
      typically used to screen for polymorphisms that vary by multiple nucleotides, it
      is equally useful for screening single nucleotide polymorphisms (SNPs). For most
      applications, it is possible to use computer software in advance to determine if
      SNPs can be differentiated using DGGE. The software can also model the effect of
      attaching a GC-rich clamp to the PCR primer to improve detection of SNPs. Once
      feasibility has been confirmed, a perpendicular DGGE can be used to identify the
      optimal denaturing gradient for the sequences of interest. Parallel gels can then
      be used to screen large numbers of samples at one time, eliminating the need for
      cloning and sequencing or direct sequencing of PCR products. This chapter
      provides step-by-step instructions on the use of DGGE and illustrates its
      application for detection of SNPs, as well as multiple nucleotide polymorphisms,
      in the major histocompatibility complex.

PMID- 19768592
TI  - Temporal temperature gradient electrophoresis for detection of single nucleotide
      polymorphisms.
AB  - The presence of single nucleotide polymorphisms (SNPs) in nuclear DNA and
      mitochondrial DNA (mtDNA) can be detected using a range of electrophoretic
      techniques, of which temporal temperature gradient electrophoresis (TTGE) is
      often the most user-friendly and reproducible. The technique operates on the same
      principle as denaturing gradient gel electrophoresis, but does not require a
      chemical gradient in the gel. Instead, TTGE relies on a steady and gradual
      increase in temperature during electrophoresis to denature and separate DNA
      sequences that differ by as little as one base pair. TTGE can be easily
      accomplished using DNA of high quality and it is a rapid-throughput method for
      SNP screening once conditions have been optimized. Detection of SNPs is, for
      example, important for the diagnosis of mitochondrial disorders such as
      heteroplasmy, the presence of more than one type of mitochondria within a cell or
      tissue. Here we describe the basic steps for TTGE and illustrate its utility for
      the detection of heteroplasmy in mtDNA control region sequences.

PMID- 19768593
TI  - Zn(II)-cyclen polyacrylamide gel electrophoresis for SNP detection.
AB  - We introduce a method for the detection of single-nucleotide polymorphisms (SNPs)
      by polyacrylamide gel electrophoresis (PAGE) with an additive Zn2+-cyclen complex
      (cyclen is 1,4,7,10-tetraazacyclododecane), called "Zn2+-cyclen-PAGE." The method
      is based on the difference in mobility of mutant DNA (of the same length) in
      PAGE, which is due to Zn2+-cyclen binding to thymine bases accompanying a total
      charge decrease and a local conformation change of target DNA. In combination
      with a polymerase chain reaction based heteroduplexing technique, the method is
      more accurate than many other conventional PAGE-based methods, as shown by clear
      gel-shifting bands because of the separation of heteroduplex and homoduplex DNAs.
      We demonstrate SNP mapping and heterozygosity screening in a human cardiac sodium
      channel gene (i.e., SCN5A) that relates to inherited arrhythmia syndromes using
      Zn2+-cyclen-PAGE.

PMID- 19768594
TI  - Phosphate-affinity polyacrylamide gel electrophoresis for SNP genotyping.
AB  - We introduce a genotyping method which relies on the use of a 1:1 mixture of 5'
      phosphate-labeled and nonlabeled allele-specific primers for polymerase chain
      reaction (PCR). The method is based on the difference in mobility of the
      phosphorylated and nonphosphorylated PCR products (possessing the same number of
      base pairs) during phosphate-affinity polyacrylamide gel electrophoresis (PAGE).
      The phosphate-affinity site in the gel is represented by an immobilized phosphate
      binding tag molecule [i.e., a polyacrylamide-bound dizinc(II) complex], which
      selectively captures the 5'-phosphate-labeled allele-specific product compared
      with the corresponding nonlabeled one. The DNA migration bands obtained can be
      visualized by ethidium bromide staining. We demonstrate the genotyping of a
      single-nucleotide polymorphism reported in a human cardiac sodium channel gene,
      SCN5A, using the phosphate-affinity PAGE.

PMID- 19768595
TI  - Estimation of SNP allele frequencies by SSCP analysis of pooled DNA.
AB  - The single strand conformation polymorphism (SSCP) method is a sensitive
      technique used to detect subtle sequence differences in PCR-amplified DNA
      fragments as separated peaks in electrophoretic analysis. In this chapter, we
      focus on SSCP analysis for quantifying polymorphic alleles rather than scanning
      for mutations. Short fragments carrying single nucleotide polymorphisms are
      amplified from individual and pooled DNA samples, then the products are labeled
      with fluorescent dyes and analyzed by automated capillary electrophoresis under
      nondenaturing conditions. Dedicated software, QSNPlite, interprets trace data of
      the electrophoresis to identify alleles of individuals and quantify these alleles
      in the pool. The software can also incorporate sequencing data to assign alleles
      at the nucleotide level. The procedures described here are being used in
      association studies that compare allele frequencies between cases and controls to
      identify genes responsible for common diseases.

PMID- 19768596
TI  - Phenylethynylpyrene excimer forming hybridization probes for fluorescence SNP
      detection.
AB  - Excimer formation is a unique feature of some fluorescent dyes (e.g., pyrene)
      which can be used for probing the proximity of biomolecules. Pyrene excimer
      fluorescence has previously been used for homogeneous detection of single
      nucleotide polymorphism (SNP) on DNA. 1-Phenylethynylpyrene (1-1-PEPy), a
      photostable pyrene derivative with redshifted fluorescence, is able to form
      excimers (emission maximum about 500-510 nm) and is well suitable for nucleic
      acid labeling. We have shown the utility of 1-1-PEPy in the excimer-forming DNA
      probes for detection of 2144A/G and 2143A/G transitions, and 2143A/C substitution
      in the 23S ribosomal RNA gene of Helicobacter pylori strains resistant to
      clarithromycin. The phenylethynylpyrene pair can be generated either from 1-1
      PEPy pseudonucleoside 4-[4-(pyren-1-ylethynyl)phenyl]-1,3-butanediol or from 2'-O
      (1-PEPy) modified nucleosides--2'-O-[3-(pyren-1-ylethynyl)benzyl]uridine and 2'-O
      [4-(pyren-1-ylethynyl)benzyl]uridine.

PMID- 19768597
TI  - The chemical cleavage of mismatch for the detection of mutations in long DNA
      fragments.
AB  - Methods to rapidly scan large regions of DNA that are not dependent on highly
      specific melting temperatures or suitable only for large-scale discovery are
      important to reduce the amount of sequencing required for DNA samples that appear
      to contain a mutation. This protocol describes the chemical cleavage of mismatch
      method to assess if a region of DNA contains a mutation and accurately localize
      the position of the mutation in the same reaction. To detect mutations, PCR
      heteroduplexes are incubated with two mismatch-specific reagents. Hydroxylamine
      modifies mismatched cytosine residues and potassium permanganate modifies
      mismatched thymine residues. The samples are then incubated with piperidine,
      which cleaves the DNA backbone at the site of the modified mismatched base.
      Cleavage products are separated by electrophoresis, revealing the identity and
      location of the mutation. The chemical cleavage of mismatch method can
      efficiently detect point mutations as well as insertions and deletions.

PMID- 19768598
TI  - Mismatch oxidation assay: detection of DNA mutations using a standard UV/Vis
      microplate reader.
AB  - Simple, low-cost mutation detection assays that are suitable for low-throughput
      analysis are essential for diagnostic applications where the causative mutation
      may be different in every family. The mismatch oxidation assay is a simple
      optical absorbance assay to detect nucleotide substitutions, insertions, and
      deletions in heteroduplex DNA. The method relies on detecting the oxidative
      modification products of mismatched thymine and cytosine bases by potassium
      permanganate as it is reduced to manganese dioxide. This approach, unlike other
      methods commonly used to detect sequence variants, does not require costly
      labeled probes or primers, toxic chemicals, or a time-consuming electrophoretic
      separation step. The oxidation rate, and hence the presence of a sequence
      variant, is detected by measuring the formation of the potassium permanganate
      reduction product (hypomanganate diester), which absorbs at the 420-nm visible
      wavelength, using a standard UV/vis microplate reader.

PMID- 19768599
TI  - High-throughput methods for SNP genotyping.
AB  - Single nucleotide polymorphisms (SNPs) are ideal markers for identifying genes
      associated with complex diseases for two main reasons. Firstly, SNPs are densely
      located on the human genome at about one SNP per approximately 500-1,000 base
      pairs. Secondly, a large number of commercial platforms are available for
      semiautomated or fully automated SNP genotyping. These SNP genotyping platforms
      serve different purposes since they differ in SNP selection, reaction chemistry,
      signal detection, throughput, cost, and assay flexibility. This chapter aims to
      give an overview of some of these platforms by explaining the technologies behind
      each platform and identifying the best application scenarios for each platform
      through cross-comparison. The readers may delve into more technical details in
      the following chapters.

PMID- 19768600
TI  - High-throughput SNP genotyping: combining tag SNPs and molecular beacons.
AB  - In the last decade, molecular beacons have emerged to become a widely used tool
      in the multiplex typing of single nucleotide polymorphisms (SNPs). Improvements
      in detection technologies in instrumentation and chemistries to label these
      probes have made it possible to use up to six spectrally distinguishable probes
      per reaction well. With the remarkable advances made in the characterization of
      human genome diversity, it has been possible to describe empirical patterns of
      SNPs and haplotype variation in the genome of diverse human populations. These
      patterns have revealed that the human genome is structured in blocks of strong
      linkage disequilibrium (LD). Because SNPs tend to be in LD with each other,
      common haplotypes share common SNPs and thus the majority of the diversity in a
      region can be characterized by typing a very small number of SNPs; so-called tag
      SNPs. Herein lies the advantage of the multiplexing ability of molecular beacons,
      since it becomes possible to use as few as 30 probes to interrogate several
      haplotypes in a high-throughput approach. Thus, through the combined use of tag
      SNPs and molecular beacons it becomes possible to type individuals for clinically
      relevant haplotypes in a high-throughput manner at a cost that is orders of
      magnitude less than that for high throughput sequencing methods.

PMID- 19768601
TI  - SNP genotyping by the 5'-nuclease reaction: advances in high-throughput
      genotyping with nonmodel organisms.
AB  - Population genetics studies play an increasingly important role in the management
      and conservation of nonmodel organisms. Unlike studies with model organisms, a
      typical population genetics study of a nonmodel organism may be conducted by
      analyzing thousands or hundreds of thousands of individuals for several dozen
      single nucleotide polymorphisms (SNPs). The use of robust, robotically mediated
      TaqMan reactions provides substantial advantages in these types of studies. We
      describe the methods and laboratory setup for analyzing a sustained high
      throughput of SNP assays in routine university or natural resource agency
      laboratories with a handful of thermal cyclers. Agencies sustain rates of nearly
      150,000 assays per week using uniplex reactions with the Applied Biosystems
      7900HT Fast Real-Time PCR System (AB 7900HT). We further describe the medium
      density array run on the BioMark from Fluidigm, which increases this rate to over
      500,000 assays per week by multiplexing 96 samples for 96 SNPs.

PMID- 19768602
TI  - The TaqMan method for SNP genotyping.
AB  - Single nucleotide polymorphisms (SNPs) are common DNA sequence variations that
      occur at single bases within the genome. SNPs have been instrumental in
      elucidating the genetic basis of common, complex diseases using genome-wide
      association studies, candidate gene case-control association studies, and genome
      wide linkage analyses. A key to these studies is genotyping of SNPs. Various
      methods for SNP genotyping have been developed. For a particular genotyping
      project, the choice of method is dependent on the number of SNPs (n) and the
      number of DNA samples (m) to be genotyped. For a genome-wide or large-scale
      project with very high n and small m, the Affymetrix SNP GeneChip and Illumina
      GoldenGate BeadChips assays are the ideal methods. For a project involving a
      small number of SNPs (small n) and a large population (high m), the TaqMan assay
      is the preferred technology as it has high throughput and is highly accurate,
      precise, time-efficient, and cost-effective. Here, we describe the detailed
      procedures for TaqMan SNP genotyping assay, including preparation of high-quality
      DNA samples, the operating protocol, clarification of technical issues, and
      discussion of several cautionary notes.

PMID- 19768603
TI  - Qualitative and quantitative genotyping using single base primer extension
      coupled with matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MassARRAY).
AB  - Matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) mass
      spectrometry (MS) has developed over the past decade into a versatile tool for
      the analysis of nucleic acids and especially as a reliable genotyping platform.
      This chapter summarizes its use in the context of the most widely used MALDI-TOF
      MS genomics platform, the Sequenom MassARRAY system. MassARRAY genotyping is
      based upon region-specific PCR followed by allele-specific single base primer
      extension reactions which are then desalted, dispensed onto a silica array
      preloaded with matrix, and the genotyping products are resolved on the basis of
      mass using MALDI-TOF MS. The platform is versatile in that it can resolve
      multiplexed reactions (40+ separate loci per reaction), acquires and interprets
      data quickly, gives a quantitative output which reflects the amount of product
      generated for each allele within an assay for multiplexed reactions, and is
      highly sensitive. These characteristics coupled with integrated software for
      sequence annotation, assay design, data interpretation, and data storage have
      lead to its wide adoption and use for multiple nucleic acid analysis applications
      in both the realm of genomics research and molecular diagnostics.

PMID- 19768604
TI  - SNP detection using trityl mass tags.
AB  - A new method suitable for single nucleotide polymorphism (SNP) detection using
      differential oligonucleotide probe extension has been developed. Sulfur-linked
      laser-cleavable trityl labels are implemented in this protocol. The method is
      based on mass spectrometry and utilizes a single surface for affinity
      purification of extended probes and matrix-independent desorption-ionization of
      the cleavable labels. The usefulness of this method for SNP genotyping is
      demonstrated.

PMID- 19768605
TI  - Putting the Invader assay to work: laboratory application and data management.
AB  - Choosing a single nucleotide polymorphism genotyping method that suits specific
      research needs is not much less of a challenge than determining the genetic
      components underlying the disease and/or trait being investigated. This is
      especially true with a long list of tempting methodologies available, as
      summarized in this book. Here, from an end-user point of view, we discuss how a
      commercially available genotyping platform, the Invader assay, can be utilized to
      meet the needs and demands of human genomic research in a laboratory.

PMID- 19768606
TI  - SNP genotyping using multiplex single base primer extension assays.
AB  - Single nucleotide polymorphisms (SNPs) are the most common form of polymorphisms
      present in the human genome. The single base primer extension (SBE) method is an
      effective and sensitive tool that can type over 30 known loci scattered
      throughout an organism's genome in a single reaction. It allows the typing of
      tetra-allelic SNPs and has been adapted to a broad range of analytical
      necessities: single-cell analysis, molecular diagnosis of monogenic diseases,
      forensic mitochondrial DNA analysis on highly degraded human remains, and high
      throughput SNP screening for population studies. Every SBE-based assay will need
      customized optimization efforts that are generally proportional to the number of
      desired SNPs typed in a single reaction. This chapter offers a detailed outline
      on which to base the design and optimization of any multiplex SBE assay that can
      then be tailored to the analytical conditions that characterize each specific
      application.

PMID- 19768607
TI  - High-throughput SNP detection based on PCR amplification on magnetic
      nanoparticles using dual-color hybridization.
AB  - A microarray-based method for detecting single nucleotide polymorphisms (SNPs)
      using solid-phase polymerase chain reaction (PCR) on magnetic nanoparticles
      (MNPs) was developed. In this method one primer with a biotin label is captured
      by streptavidin-coated MNPs (SA-MNPs), and the PCR products are directly
      amplified on the surface of SA-MNPs in a 96-well plate. The samples are further
      probed by hybridization with a pair of dual-color probes to determine SNP. The
      genotype of each sample can be simultaneously identified by scanning the
      microarray printed with the denatured fluorescent probes. All the reactions can
      be performed in the same reaction volume without the necessity of purification of
      intermediates. This approach represents a novel, simple, and labor-saving method
      for SNP genotyping and can be applied in automation system(s) to achieve high
      throughput SNP detection.

PMID- 19768608
TI  - Restriction enzyme analysis of PCR products.
AB  - Progress in single nucleotide polymorphism (SNP) detection technologies has
      provided information for SNP-based studies, such as identification of candidate
      genes for the complex genetic diseases, pharmacogenetic analysis, drug
      development, population genetics, evolutionary studies, and forensic
      investigations. SNP detection is performed by many methods, including
      hybridization, allele-specific polymerase chain reaction (PCR), primer extension,
      oligonucleotide ligation, direct DNA sequencing, and endonuclease cleavage. Each
      of these methods has its specific advantages and disadvantages. Here we introduce
      the PCR-restriction fragment length polymorphism (RFLP) method, which has certain
      advantages over many other techniques used for analysis of SNPs. The PCR-RFLP
      method allows very rapid, simple, and inexpensive detection of point mutations
      within the sequences of PCR products. The mutation is discriminated by the
      specific restriction endonuclease and is identified by gel electrophoresis
      followed by staining with ethidium bromide. This convenient and simple method is
      useful in a small basic research study.

PMID- 19768609
TI  - Allele-specific PCR in SNP genotyping.
AB  - The increasing need for large-scale genotyping applications of single nucleotide
      polymorphisms (SNPs) in model and nonmodel organisms requires the development of
      low-cost technologies accessible to minimally equipped laboratories. The method
      presented here allows efficient discrimination of SNPs by allele-specific PCR in
      a single reaction with standard PCR conditions. A common reverse primer and two
      forward allele-specific primers with different tails amplify two allele-specific
      PCR products of different lengths, which are further separated by agarose gel
      electrophoresis. PCR specificity is improved by the introduction of a
      destabilizing mismatch within the 30 end of the allele-specific primers. This is
      a simple and inexpensive method for SNP detection that does not require PCR
      optimization.

PMID- 19768610
TI  - Modified multiple primer extension method.
AB  - A multiple primer extension (MPEX) was originally developed for the
      hybridization, extension, and amplification of a DNA template on a planar
      substrate by Kinoshita et al. in 2006. Herein we present a modified MPEX method
      refined by our group for single nucleotide polymorphism (SNP) detection. In this
      method, hybridization and extension reactions are performed on a plastic S-BIO
      PrimeSurface substrate, with a biocompatible polymer. Its surface chemistry
      offers extraordinarily stable thermal properties, as well as chemical properties
      advantageous for enzymatic reactions on the surface. To visualize allele-specific
      PCR products on the surface, biotin-dUTP was incorporated into newly synthesized
      complementary strands during the extension reaction. The products were ultimately
      detected by carrying out a colorimetric reaction with a substrate solution
      containing 5-bromo-4-chloro-3-indolyl phosphate/nitro blue tetrazolium. We have
      further successfully combined this method with multiplex PCR. We demonstrate the
      advantages of this combined method by analyzing representative SNPs on different
      linkage disequilibrium blocks of the micro opioid receptor gene (OPRM1), which is
      a marker gene for pain threshold.

PMID- 19768611
TI  - Detection of SNP by the isothermal smart amplification method.
AB  - The complexity of molecular diagnostic assays is a significant barrier to
      employment in point-of-care diagnostics, despite the growing need for such
      technologies. We have developed a sensitive, accurate, rapid, and simple DNA
      amplification scheme that shows potential for translational medicine from
      pharmacogenomics-based drug discovery through to point-of-care diagnostics.
      Called the "Smart Amplification process 2" (SmartAmp 2), the method is
      isothermal, and employs a unique primer design and background suppression
      technology that can amplify target sequences from crude cell lysates. The
      specificity of the SmartAmp 2 assay enables detection of single-nucleotide
      differences such as somatic mutations in tumors and single nucleotide
      polymorphism (SNP) variants. Because mismatch amplification can be completely
      suppressed in SmartAmp 2, a reliable diagnostic result can be achieved based
      exclusively on amplification alone. Furthermore, mutation detection and SNP
      genotypes can be obtained in as little as 30-40 min from sample preparation of
      raw blood or tissue specimens.

PMID- 19768612
TI  - Biomass supply logistics and infrastructure.
AB  - Feedstock supply system encompasses numerous unit operations necessary to move
      lignocellulosic feedstock from the place where it is produced (in the field or on
      the stump) to the start of the conversion process (reactor throat) of the
      biorefinery. These unit operations, which include collection, storage,
      preprocessing, handling, and transportation, represent one of the largest
      technical and logistics challenges to the emerging lignocellulosic biorefining
      industry. This chapter briefly reviews the methods of estimating the quantities
      of biomass, followed by harvesting and collection processes based on current
      practices on handling wet and dry forage materials. Storage and queuing are used
      to deal with seasonal harvest times, variable yields, and delivery schedules.
      Preprocessing can be as simple as grinding and formatting the biomass for
      increased bulk density or improved conversion efficiency, or it can be as complex
      as improving feedstock quality through fractionation, tissue separation, drying,
      blending, and densification. Handling and transportation consists of using a
      variety of transport equipment (truck, train, ship) for moving the biomass from
      one point to another. The chapter also provides typical cost figures for harvest
      and processing of biomass.

PMID- 19768613
TI  - Selecting, establishing, and managing switchgrass (Panicum virgatum) for
      biofuels.
AB  - Switchgrass is being widely considered as a feedstock for biofuel production.
      Much remains to be learned about ideal feedstock characteristics, but switchgrass
      offers many advantages already and can perhaps be manipulated to offer more. When
      planning to grow switchgrass, select a cultivar that is well adapted to the
      location - generally a lowland cultivar for the southern United States and an
      upland cultivar at higher latitudes. Plant non-dormant seed after soils are well
      warmed, preferably with no-till methods and always with good weed control. Except
      for weeds, few pests appear to be widespread; but disease and insect pests could
      become more important as acreages increase. Fertilization requirements are
      relatively low, with 50 kg N/ha/year being a good "generic" recommendation where
      a single harvest is taken after plants have senesced; more will be needed if
      biomass is harvested while still green. Switchgrass should be harvested no more
      than twice per year and may generally be expected to produce 12 to >or=20
      mg/ha/year across its usual range of distribution. A single harvest may provide
      for maximum sustainable yields - especially if the harvest is taken after tops
      die back at the end of the season. Several harvesting technologies are available,
      but the preferred technology may depend on logistics and economics associated
      with the local processing point, or biorefinery.

PMID- 19768614
TI  - Agronomic experiences with Miscanthus x giganteus in Illinois, USA.
AB  - Since 2002, researchers at the University of Illinois, Urbana-Champaign,
      Illinois, have been studying the perennial warm-season grass Miscanthus x
      giganteus (M. x g.) to determine its potential as a biomass feedstock. M. x g.
      originated in Japan and is a hybrid believed to have M. sinensis and M.
      sacchariflorus as its parents. Until recently, it was used as a landscape plant
      in the United States, but it is now the subject of research interest because of
      its potentially great biomass production. In central Illinois, M. x g. begins
      growth in April, typically reaches 2 m by the end of May, and is normally greater
      than 3 m by the end of September. The grass is sterile and propagated asexually
      using plantlets produced in tissue culture or by rhizome divisions. Following
      field planting, it generally takes at least three growing seasons to become fully
      established and reach optimal biomass production. In central Illinois, the
      senesced stems are harvested from early December through early March and can
      potentially be treated to produce ligno-cellulosic ethanol. In University of
      Illinois, research started in 2002. M. x g. produced an annual average of 22.0
      t/ha in northern Illinois, 34.7 t/ha in central Illinois, and 35.4 t/ha in
      southern Illinois per year in 2004, 2005, and 2006.

PMID- 19768615
TI  - Genetic transformation of switchgrass.
AB  - Switchgrass (Panicum virgatum L.) is a highly productive warm-season C4 species
      that is being developed into a dedicated biofuel crop. This chapter describes a
      protocol that allows the generation of transgenic switchgrass plants by
      Agrobacterium tumefaciens-mediated transformation. Embryogenic calluses induced
      from caryopses or inflorescences were used as explants for inoculation with A.
      tumefaciens strain EHA105. Hygromycin phosphotransferase gene (hph) was used as
      the selectable marker and hygromycin was used as the selection agent. Calluses
      resistant to hygromycin were obtained after 5-6 weeks of selection. Soil-grown
      switchgrass plants were regenerated about 6 months after callus induction and
      Agrobacterium-mediated transformation.

PMID- 19768616
TI  - Lignocellulosic biomass pretreatment using AFEX.
AB  - Although cellulose is the most abundant organic molecule, its susceptibility to
      hydrolysis is restricted due to the rigid lignin and hemicellulose protection
      surrounding the cellulose micro fibrils. Therefore, an effective pretreatment is
      necessary to liberate the cellulose from the lignin-hemicellulose seal and also
      reduce cellulosic crystallinity. Some of the available pretreatment techniques
      include acid hydrolysis, steam explosion, ammonia fiber expansion (AFEX),
      alkaline wet oxidation, and hot water pretreatment. Besides reducing
      lignocellulosic recalcitrance, an ideal pretreatment must also minimize formation
      of degradation products that inhibit subsequent hydrolysis and fermentation. AFEX
      is an important pretreatment technology that utilizes both physical (high
      temperature and pressure) and chemical (ammonia) processes to achieve effective
      pretreatment. Besides increasing the surface accessibility for hydrolysis, AFEX
      promotes cellulose decrystallization and partial hemicellulose depolymerization
      and reduces the lignin recalcitrance in the treated biomass. Theoretical glucose
      yield upon optimal enzymatic hydrolysis on AFEX-treated corn stover is
      approximately 98%. Furthermore, AFEX offers several unique advantages over other
      pretreatments, which include near complete recovery of the pretreatment chemical
      (ammonia), nutrient addition for microbial growth through the remaining ammonia
      on pretreated biomass, and not requiring a washing step during the process which
      facilitates high solid loading hydrolysis. This chapter provides a detailed
      practical procedure to perform AFEX, design the reactor, determine the mass
      balances, and conduct the process safely.

PMID- 19768617
TI  - Pretreatment of biomass by aqueous ammonia for bioethanol production.
AB  - The methods of pretreatment of lignocellulosic biomass using aqueous ammonia are
      described. The main effect of ammonia treatment of biomass is delignification
      without significantly affecting the carbohydrate contents. It is a very effective
      pretreatment method especially for substrates that have low lignin contents such
      as agricultural residues and herbaceous feedstock. The ammonia-based pretreatment
      is well suited for simultaneous saccharification and co-fermentation (SSCF)
      because the treated biomass retains cellulose as well as hemicellulose. It has
      been demonstrated that overall ethanol yield above 75% of the theoretical maximum
      on the basis of total carbohydrate is achievable from corn stover pretreated with
      aqueous ammonia by way of SSCF. There are two different types of pretreatment
      methods based on aqueous ammonia: (1) high severity, low contact time process
      (ammonia recycle percolation; ARP), (2) low severity, high treatment time process
      (soaking in aqueous ammonia; SAA). Both of these methods are described and
      discussed for their features and effectiveness.

PMID- 19768618
TI  - Liquid hot water pretreatment of cellulosic biomass.
AB  - Lignocellulosic biomass is an abundant and renewable resource for fuel ethanol
      production. However, the lignocellulose is recalcitrant to enzymatic hydrolysis
      because of its structural complexity. Controlled-pH liquid hot water (LHW)
      pretreatment of cellulosic feedstock improves its enzymatic digestibility by
      removing hemicellulose and making the cellulose more accessible to cellulase
      enzymes. The removed hemicellulose is solubilized in the liquid phase of the
      pretreated feedstock as oligosaccharides. Formation of monomeric sugars during
      the LHW pretreatment is minimal. The LHW pretreatment is carried out by cooking
      the feedstock in process water at temperatures between 160 and 190 degrees C and
      at a pH of 4-7. No additional chemicals are needed. This chapter presents the
      detailed procedure of the LHW pretreatment of lignocellulosic biomass.

PMID- 19768619
TI  - Dilute acid and autohydrolysis pretreatment.
AB  - Exposure of cellulosic biomass to temperatures of about 120-210 degrees C can
      remove most of the hemicellulose and produce cellulose-rich solids from which
      high glucose yields are possible with cellulase enzymes. Furthermore, the use of
      dilute sulfuric acid in this pretreatment operation can increase recovery of
      hemicellulose sugars substantially to about 85-95% of the maximum possible versus
      only about 65% if no acid is employed. The use of small-diameter tubes makes it
      possible to employ high solids concentrations similar to those preferred for
      commercial operations, with rapid heat-up, good temperature control, and accurate
      closure of material balances. Mixed reactors can be employed to pretreat larger
      amounts of biomass than possible in such small-diameter tubes, but solids
      concentrations are limited to about 15% or less to provide uniform temperatures.
      Pretreatment of large amounts of biomass at high solids concentrations is best
      carried out using direct steam injection and rapid pressure release, but closure
      of material balances in such "steam gun" devices is more difficult. Although flow
      of water alone or containing dilute acid is not practical commercially, such flow
      through configurations provide valuable insight into biomass deconstruction
      kinetics not possible in the batch tubes, mixed reactors, or steam gun systems.

PMID- 19768620
TI  - Lime pretreatment.
AB  - Lime pretreatment has proven to be a useful method for selectively reducing the
      lignin content of lignocellulosic biomass without significant loss in
      carbohydrates, thus realizing an important increase in biodigestibility. In lime
      pretreatment, the biomass is pretreated with calcium hydroxide and water under
      different conditions of temperature and pressure. It can be accomplished in one
      of three fashions: (1) short-term pretreatment that lasts up to 6 h, requires
      temperatures of 100-160 degrees C, and can be applied with or without oxygen
      (pressure approximately 200 psig); (2) long-term pretreatment taking up to 8
      weeks, requiring only 55-65 degrees C, and capable of running with or without air
      (atmospheric pressure); and (3) simple pretreatment requiring 1 h in boiling
      water, without air or oxygen. Nonoxidative conditions are effective at low lignin
      contents (below approximately 18% lignin), whereas oxidative conditions are
      required for high lignin contents (above approximately 18% lignin).

PMID- 19768621
TI  - Analytical characterization of fermentation inhibitors in biomass pretreatment
      samples using liquid chromatography, UV-visible spectroscopy, and tandem mass
      spectrometry.
AB  - A variety of chemicals are produced upon pretreatment of lignocellulosic biomass.
      Aliphatic acids, aromatic acids, aldehydes, and phenolic compounds are of
      particular interest due to their presumed inhibitory influence on downstream
      enzymatic or microbial steps in biomass-to-ethanol conversion. Herein, we
      describe a series of analytical protocols that collectively enable quantitative
      monitoring of 40 potential fermentation inhibitors in biomass pretreatment
      samples. Solid samples are accommodated by first employing pressurized fluid
      extraction to generate an aqueous "wash stream." Sample preparation for liquids
      involves an initial precipitation-filtration step, followed by liquid-liquid
      extraction and reconstitution of extracts in water. Samples are analyzed using
      high-performance liquid chromatography (HPLC) in combination with ultraviolet
      (UV) absorbance and tandem mass spectrometry (MS/MS) detection. A standard
      addition approach is utilized for quantitation to alleviate complications arising
      from co-extracted sample matrix.

PMID- 19768622
TI  - Biomass compositional analysis for energy applications.
AB  - In its broadest definition, biomass can be described as all material that was or
      is a part of a living organism. For renewable energy applications, however, the
      definition of biomass is usually limited to include only materials that are plant
      derived such as agricultural residues (e.g., wheat straw, corn stover) by
      products of industrial processes (e.g., sawdust, sugar cane bagasse, pulp
      residues, distillers grains), or dedicated energy crops (e.g., switchgrass,
      sorghum, Miscanthus, short-rotation woody crops). This chapter describes
      analytical methods developed to measure plant components with an emphasis on the
      measurement of components that are important for biomass conversion. The methods
      described here can be viewed as a portfolio of analytical methods, with
      consistent assumptions and compatible sample preparation steps, selected for
      simplicity, robust application, and the ability to obtain a summative mass
      closure on most samples that accurately identifies greater than 95% of the mass
      of a plant biomass sample. The portfolio of methods has been successfully applied
      to a wide variety of biomass feedstock as well as liquid and solid fractions of
      both thermochemical pretreatment and enzymatic saccharification (1).

PMID- 19768623
TI  - High-throughput screening of plant cell-wall composition using pyrolysis
      molecular beam mass spectroscopy.
AB  - We describe a high-throughput method for estimating cell-wall chemistry traits
      using analytical pyrolysis. The instrument used to perform the high-throughput
      cell-wall chemistry analysis consists of a commercially available pyrolysis unit
      and autosampler coupled to a custom-built molecular beam mass spectrometer. The
      system is capable of analyzing approximately 42 biomass samples per hour. Lignin
      content and syringyl to guaiacol (S/G) ratios can be estimated directly from the
      spectra and differences in cell wall chemistry in large groups of samples can
      easily be identified using multivariate statistical data analysis methods. The
      utility of the system is demonstrated on a set of 800 greenhouse-grown poplar
      trees grown under two contrasting nitrogen treatments. High-throughput analytical
      pyrolysis was able to determine that the lignin content varied between 13 and 28%
      and the S/G ratio ranged from 0.5 to 1.5. There was more cell-wall chemistry
      variation in the plants grown under high nitrogen conditions than trees grown
      under nitrogen-deficiency conditions. Analytical pyrolysis allows the user to
      rapidly screen large numbers of samples at low cost, using very little sample
      material while producing reliable and reproducible results.

PMID- 19768624
TI  - Preparation and analysis of biomass lignins.
AB  - Lignin, comprised primarily of three randomly polymerized phenylpropenyl
      monomers, is, arguably, the second most common organic molecule on earth. In
      current biorefinery applications, lignin is burned, usually in concentrated
      pulping or hydrolysis liquor, as a source of process steam and both internal and
      exported electricity. The aromatic content of lignin makes it a potentially
      attractive feedstock for high-value aromatic chemicals, polymers, and carbon
      products (graphite, activated carbon, and carbon fiber). Revenue from production
      of lignin-based chemicals could play a major role in biorefinery profitability if
      cost-effective methods for lignin separation and purification can be developed.
      This chapter presents descriptions of methods for assessing and purifying
      biorefinery lignins so that they can be evaluated for use as feedstock for
      production of chemical products. Areas covered are: (1) initial evaluations of as
      received lignin samples (visual, microscopic, separable organics); (2) analysis
      of common contaminants (bulk and filterable ash and particulate contaminants in
      liquid and dry lignin samples); (3) preparation of lignins for experimental use
      as chemical feedstock (prefiltration, filtration using bench-scale chemical
      apparatus and larger scale bag filters, one-step lignin precipitation, two-step
      carbohydrate and lignin precipitation, desalting of dry powdered or precipitated
      lignin, and lyophilization). These methods have been used successfully at the
      bench scale to produce the 1-50 kg amounts of wood and grass lignins typically
      required for bench-scale assessment as chemical feedstocks.

PMID- 19768625
TI  - Cellulase assays.
AB  - Cellulose is a heterogeneous polysaccharide, and its enzymatic hydrolysis
      requires endoglucanase, exoglucanase (cellobiohydrolase), and beta-glucosidase to
      work together. We summarize the most commonly used assays for individual enzymes
      and cellulase mixture.

PMID- 19768626
TI  - Assessing cellulase performance on pretreated lignocellulosic biomass using
      saccharification and fermentation-based protocols.
AB  - Cellulase enzyme is a key cost component in the production of fuels and chemicals
      from lignocellulosic biomass. Cellulolytic ability of the enzyme preparation is
      often measured by activity assays using model substrates such as filter paper.
      Using lignocellulosic biomass as the substrate to assess enzyme performance has
      the potential of being more process relevant. We describe two procedures that use
      washed pretreated cellulosic material to measure the efficacy of cellulase
      enzymes. First, a saccharification assay that measures glucose yield as a
      function of the amount of cellulase used in the process. And second, the
      simultaneous saccharification and fermentation (SSF) assay measures cellulase
      performance by the amount of ethanol produced from enzymatic hydrolysis of the
      cellulosic material. You can use both assays to screen cellulases under a variety
      of substrate types, loadings, and process conditions.

PMID- 19768627
TI  - Basic laboratory culture methods for anaerobic bacteria.
AB  - Oxygen is either limiting or absent in many ecosystems. Anaerobic bacteria are
      often key players in such environments and these organisms have important roles
      in geo-elemental cycling, agriculture, and medicine. The metabolic versatility of
      anaerobes is exploited in a variety of industrial processes including fermented
      food production, biochemical synthesis, and bioremediation. There has been recent
      considerable interest in developing and enhancing technologies that employ
      anaerobes as biocatalysts. The study of anaerobic bacteria requires specialized
      techniques, and specific methods are described for the culture and manipulation
      of these microbes.

PMID- 19768628
TI  - Simultaneous saccharification and fermentation and partial saccharification and
      co-fermentation of lignocellulosic biomass for ethanol production.
AB  - Ethanol production by fermentation of lignocellulosic biomass-derived sugars
      involves a fairly ancient art and an ever-evolving science. Production of ethanol
      from lignocellulosic biomass is not avant-garde, and wood ethanol plants have
      been in existence since at least 1915. Most current ethanol production relies on
      starch- and sugar-based crops as the substrate; however, limitations of these
      materials and competing value for human and animal feeds is renewing interest in
      lignocellulose conversion. Herein, we describe methods for both simultaneous
      saccharification and fermentation (SSF) and a similar but separate process for
      partial saccharification and cofermentation (PSCF) of lignocellulosic biomass for
      ethanol production using yeasts or pentose-fermenting engineered bacteria. These
      methods are applicable for small-scale preliminary evaluations of ethanol
      production from a variety of biomass sources.

PMID- 19768629
TI  - Biodiesel: small scale production and quality requirements.
AB  - Biodiesel is produced by reacting vegetable oils or animal fats with alcohol in
      the presence of an alkaline catalyst. The resulting methyl esters, which are the
      biodiesel fuel, are separated from the by-product glycerin, and then washed with
      water and dehydrated to produce fuel that must meet standardized specifications.
      Degraded oils containing high levels of free fatty acids can also be converted to
      biodiesel, but pretreatment with acid-catalyzed esterification is required. The
      resulting fuel is suitable for use as a neat fuel in diesel engines or blended
      with conventional diesel fuel.

PMID- 19768630
TI  - Fine mapping of Plasmodium falciparum ribosomal phosphoprotein PfP0 revealed
      sequences with highly specific binding activity to human red blood cells.
AB  - The Plasmodium falciparum P0 ribosomal phosphoprotein (PfP0) was identified for
      the first time by screening a cDNA expression library of P. falciparum parasites
      with sera from malaria-immune individuals. Due to its localization on the surface
      of different parasite life-cycle stages (merozoites and gametocytes) and its
      recognition by invasion-blocking antibodies, PfP0 has been considered a potential
      malaria-vaccine component. In this study, 16 20-mer-long synthetic peptides
      spanning the entire PfP0 sequence were evaluated by means of receptor-ligand
      assays with human red blood cells (RBCs) in order to determine the role played by
      these peptides in the invasion process. Four RBC high-activity binding peptides
      (HABPs), located mostly toward the N-terminal region, were identified: HABP 33898
      ((1)MAKLSKQQKKQMYIEKLSSL(20)), HABP 33900 ((41)ASVRKSLRGKATILMGKNTRY(60)), HABP
      33901 ((61)IRTALKKNLQAVPQIEKLLPY (80)), and HABP 33906
      ((161)LIKQGEKVTASSATLLRKFNY(180)). The binding pattern of HABPs 33898 and 33906
      to enzyme-treated RBCs suggests receptors of protein nature for these two HABPs,
      one of which could correspond to a common 58-kDa RBC membrane protein, as
      indicated by results of cross-linking assays. Both HABPs exhibited high content
      of alpha-helical features and prevented P. falciparum merozoite invasion to RBCs
      in vitro by up to 91%. The invasion-blocking ability reported here for these PfP0
      HABPs supports their inclusion in immunological studies with the aim of assessing
      their potential as candidates for a vaccine against P. falciparum malaria.

PMID- 19768632
TI  - New isolates of carnation Italian ringspot virus differ from the original one by
      having replication-associated proteins with a typical tombusvirus-like N-terminus
      and by inducing peroxisome- rather than mitochondrion-derived multivesicular
      bodies.
AB  - Five new isolates of carnation Italian ringspot virus (CIRV) from cherry trees,
      Gypsophila and surface water differ from the original carnation isolate (CIRV
      car) and also from Pelargonium necrotic spot virus (PelNSV) by having an ORF
      1/ORF1-RT with a typical tombusvirus-like 5'end and by inducing the formation of
      peroxisome- rather than mitochondrion-derived multivesicular bodies (MVBs). This
      supports with natural isolates earlier conclusions reached by others with
      artificially produced hybrid viruses that the 5'end of ORF 1 determines from
      which organelle the MBVs will be derived. CIRV-car might have resulted from a
      natural recombination event with genome elements of a PelNSV-like virus.

PMID- 19768631
TI  - Molecular characterisation and recent evolution of myxoma virus in Spain.
AB  - Myxoma virus and the European rabbit are one of the best-studied examples of
      coevolution of pathogen virulence and host resistance. Since the introduction of
      the virus in Spain in 1953, a decrease in its virulence has been observed;
      however, most strains are still considered highly virulent. To determine whether
      this attenuation is due to molecular differences, and to characterise the field
      strains in Spain and the genetic changes that have occurred since the
      introduction of the virus, we analysed 7,741 bp in 97 virus samples from 12
      localities. We found an extremely low genetic variability and an absence of a
      geographic structure. We defined 35 haplotypes, none of which were identical to
      the original Lausanne strain. Three genetic groups were determined and were found
      to occur at different frequencies in different locations. Overall, virus
      evolution deviated from neutrality and did not conform to a strict molecular
      clock, probably due to the existence of a strong selective pressure that acts
      differently across the viral genome.

PMID- 19768633
TI  - Fatigue and autonomic dysfunction in non-alcoholic fatty liver disease.
AB  - BACKGROUND: Fatigue is a significant symptom in nonalcoholic fatty liver disease
      (NAFLD) that impacts upon quality of life and is unrelated to liver disease
      severity. We examined the relationship between parameters of blood pressure
      regulation with perception of fatigue in NAFLD. METHODS: Thirty-four non-diabetic
      subjects with histologically proven, non-cirrhotic NAFLD (26 [77%] males and 8
      [23%] females) (mean +/- SD age 54 +/- 11) and 34 age, sex and BMI matched non
      diabetic controls underwent subjective and objective evaluation of cardiovascular
      autonomic function (24 h blood pressure and head up tilt testing). All subjects
      completed the fatigue impact scale. RESULTS: The NAFLD group had significantly
      higher autonomic symptom burden assessed using the orthostatic grading scale
      (OGS) compared to controls (4 +/- 4 vs. 1 +/- 2; p = 0.0003). Increasing
      orthostatic symptoms correlated with increasing fatigue (p = 0.006; r(2) = 0.3).
      Fatigue in NAFLD correlated inversely with 24 h measurement of systolic,
      diastolic and mean blood pressures (all p < 0.03; r(2) = 0.2). This relationship
      was predominantly related to lower blood pressure at night (p < 0.003; r(2) =
      0.3). On head up tilt testing 57% of the NAFLD group had neurally-mediated
      hypotension (vasovagal syncope and/or orthostatic hypotension) (p = 0.006
      compared to controls). The degree of blood pressure drop in response to standing
      correlated with fatigue severity (p = 0.008; r(2) = 0.3) and the autonomic
      symptom burden (OGS) (p = 0.03; r(2) = 0.2). CONCLUSION: Autonomic symptoms are
      prevalent in NAFLD and associate with objective measures of autonomic
      dysfunction. Fatigue in NAFLD is associated with lower blood pressure and
      autonomic dysfunction. Studies are needed to determine whether this is a
      potential therapeutic target for fatigue in NAFLD.

PMID- 19768634
TI  - Bortezomib sensitizes primary human esthesioneuroblastoma cells to TRAIL-induced
      apoptosis.
AB  - TNF-related apoptosis-inducing ligand (TRAIL), a promising novel anti-cancer
      cytokine of the TNF superfamily, and Bortezomib, the first-in-class clinically
      used proteasome inhibitor, alone or in combination have been shown to efficiently
      kill numerous tumor cell lines. However, data concerning primary human tumor
      cells are very rare. Using primary esthesioneuroblastoma cells we analyzed the
      anti-tumor potential and the mechanism employed by Bortezomib in combination with
      TRAIL for the treatment of this rare but aggressive tumor. Expression of
      components of the TRAIL pathway was analyzed in tumor specimens and isolated
      primary tumor cells at the protein level. Cells were treated with TRAIL,
      Bortezomib, and a combination thereof, and apoptosis induction was quantified.
      Clonogenicity assays were performed to elucidate the long-term effect of this
      treatment. Despite expressing all components of the TRAIL pathway, freshly
      isolated primary esthesioneuroblastoma cells were completely resistant to TRAIL
      induced apoptosis. They could, however, be very efficiently sensitized by
      subtoxic doses of Bortezomib. The influence of Bortezomib on the TRAIL pathway
      was analyzed and showed upregulation of TRAIL death receptor expression,
      enhancement of the TRAIL death-inducing signaling complex (DISC), and
      downregulation of anti-apoptotic proteins of the TRAIL pathway. Of clinical
      relevance, TRAIL-resistant primary tumor cells could be repeatedly sensitized by
      Bortezomib, providing the basis for repeated clinical application schedules. This
      is the first report on the highly synergistic induction of apoptosis in primary
      esthesioneuroblastoma cells by Bortezomib and TRAIL. This combination, therefore,
      represents a promising novel therapeutic option for esthesioneuroblastoma.

PMID- 19768635
TI  - Plumbagin inhibits TPA-induced MMP-2 and u-PA expressions by reducing binding
      activities of NF-kappaB and AP-1 via ERK signaling pathway in A549 human lung
      cancer cells.
AB  - This study first investigates the anti-metastatic effect of plumbagin (5-hydroxy
      2-methyl-1,4-naphthoquinone) on 12-O-tetradecanoylphorbol-13-acetate (TPA)
      induced MMPs and u-PA expressions in human lung cancer cells, A549. First, the
      result demonstrated plumbagin could inhibit TPA induced the abilities of the
      adhesion, invasion, and migration by cell-matrix adhesion assay and Boyden
      chamber assay. Data also showed plumbagin could inhibit the activation of
      extracellular signal-regulated kinase 1 and 2 (ERK1/2) involved in the down
      regulating enzyme activities, protein and messenger RNA levels of matrix
      metalloproteinase-2 (MMP-2), and urokinase-type plasminogen activator (u-PA)
      induced by TPA. Next, plumbagin also strongly inhibited TPA-induced
      phosphorylation and degradation of inhibitor of kappaBalpha (IkappaBalpha), and
      the nuclear levels of nuclear factor kappa B (NF-kappaB), c-Fos, and c-Jun. Also,
      a dose-dependent inhibition on the binding abilities of NF-kappaB and activator
      protein-1 (AP-1) by plumbagin treatment was further observed. Further, the
      treatment of specific inhibitor for ERK (U0126) to A549 cells could inhibit TPA
      induced MMP-2 and u-PA expressions along with an inhibition on cell invasion and
      migration. Presented data reveals that plumbagin is a novel, effective, anti
      metastatic agent that functions by down-regulating MMP-2 and u-PA gene
      expressions.

PMID- 19768636
TI  - First solid state alkaline-earth complexes of monensic acid A (MonH): crystal
      structure of [M(Mon)2(H (2)O)2] (M = Mg, Ca), spectral properties and
      cytotoxicity against aerobic Gram-positive bacteria.
AB  - Alkaline-earth metal complexes of the monoanionic form of the polyether ionophore
      monensin A were isolated for the first time in solid state and were structurally
      characterized using various spectroscopic methods (IR, NMR, FAB-MS). The
      stoichiometric reaction of monensic acid (MonH) with M(2+) (M = Mg, Ca) in the
      presence of an organic base leads to the formation of mononuclear complexes of
      composition [M(Mon)(2)(H(2)O)(2)]. The structures of magnesium (1) and calcium
      (2) monensin complexes in the solid state were established by single crystal X
      ray crystallography. The complexes crystallize as [Mg(Mon)(2)(H(2)O)(2)]x5MeCN
      (1) and [Ca(Mon)(2)(H(2)O)(2)]xH(2)Ox5MeCN (2) in the monoclinic P21 space group.
      The alkaline-earth metal ion is placed in a distorted octahedral environment,
      defined by two monensin anions acting as bidentate ligands in the equatorial
      plane of the complex as well as by two water molecules occupying the axial
      positions of the inner coordination sphere. The bactericidal activity of 1 and 2
      was evaluated against aerobic Gram-positive microorganisms applying the double
      layer agar hole diffusion method.

PMID- 19768638
TI  - Cost of atrial fibrillation in United States managed care organizations.
AB  - INTRODUCTION: Atrial fibrillation (AF) has been shown to be associated with high
      healthcare costs; however, limited data are available from large-scale studies
      quantifying the overall cost burden of AF in the USA. We therefore aimed to
      provide an up to date estimate of the overall per-patient costs of AF in managed
      care organizations across the USA. METHODS: This retrospective cohort study used
      claims data from the Integrated Healthcare Information Systems National Managed
      Care Benchmark Database from January 2005 to December 2006. Patients included in
      the analysis were aged > or =20 years and had at least two outpatient AF-related
      claims without hospitalization, or a hospitalization with a primary or secondary
      discharge diagnosis of AF in 2005. AF-related inpatient and outpatient costs over
      12 months from the initial outpatient claim or first hospitalization were
      examined. For secondary AF hospitalizations, incremental costs associated with AF
      were measured by comparing costs for patients with AF with a group of matched
      controls hospitalized without AF. RESULTS: In total, 35,255 patients diagnosed as
      having AF (5008 with a primary AF diagnosis, 10,776 with a secondary AF
      diagnosis, 19,471 with outpatient-managed AF), and 20,571 controls without AF,
      were included in the analysis. Over 12 months, for primary AF hospitalization
      patients, inpatient costs were $11,306.53 and outpatient costs were $2826.78
      (total $14,133.30) per patient. For hospitalized patients with secondary AF,
      incremental AF-related inpatient costs were $5181.19 and outpatient costs were
      $1376.33 (total $6557.52). For AF patients with outpatient management in 2005, 12
      month AF-related costs were $2177.30 ($175.47 for AF hospitalizations in 2006 and
      $2001.85 for outpatient costs). CONCLUSIONS: Overall costs of AF in the US
      managed care organizations are high. Costs are primarily due to inpatient
      expenses. Improved disease management strategies to reduce AF-related
      hospitalizations and decrease the overall cost burden of AF are needed.

PMID- 19768639
TI  - Phosphodiesterase type 5 inhibitors in pulmonary arterial hypertension.
AB  - Pulmonary arterial hypertension (PAH) is a rare disease characterized by vascular
      proliferation and remodeling, resulting in a progressive increase in pulmonary
      arterial resistance, right heart failure, and death. The pathogenesis of PAH is
      multifactorial, with endothelial cell dysfunction playing an integral role. This
      endothelial dysfunction is characterized by an overproduction of vasoconstrictors
      and proliferative factors, such as endothelin-1, and a reduction of vasodilators
      and antiproliferative factors, such prostacyclin and nitric oxide.
      Phosphodiesterase type 5 (PDE-5) is implicated in this process by inactivating
      cyclic guanosine monophosphate, the nitric oxide pathway second messenger. PDE-5
      is abundantly expressed in lung tissue, and appears to be upregulated in PAH.
      Three oral PDE-5 inhibitors are available (sildenafil, tadalafil, and vardenafil)
      and are the recommended first-line treatment for erectile dysfunction.
      Experimental studies have shown the beneficial effects of PDE-5 inhibitors on
      pulmonary vascular remodeling and vasodilatation, justifying their investigation
      in PAH. Randomized clinical trials in monotherapy or combination therapy have
      been conducted in PAH with sildenafil and tadalafil, which are therefore
      currently the approved PDE-5 inhibitors in PAH treatment. Sildenafil and
      tadalafil significantly improve clinical status, exercise capacity, and
      hemodynamics of PAH patients. Combination therapy of PDE-5 inhibitors with
      prostacyclin analogs and endothelin receptor antagonists may be helpful in the
      management of PAH although further studies are needed in this area. The third PDE
      5 inhibitor, vardenafil, is currently being investigated in PAH. Side effects are
      usually mild and transient and include headache, flushing, nasal congestion,
      digestive disorders, and myalgia. Mild and moderate renal or hepatic failure does
      not significantly affect the metabolism of PDE-5 inhibitors, whereas
      coadministration of bosentan decreases sildenafil and tadalafil plasma levels.
      Due to their clinical effectiveness, tolerance profile, and their oral
      administration, sildenafil and tadalafil are two of the recommended first-line
      therapies for PAH patients in World Health Organization functional classes II or
      III.

PMID- 19768637
TI  - Molecular imaging in clinical trials.
AB  - Imaging of biological processes using specific molecular probes allows
      exploration of the mechanism of action and efficacy for new therapies. This
      molecular imaging has made use of modalities including single photon emission
      computed tomography (SPECT), positron emission tomography (PET), magnetic
      resonance imaging (MRI), and optical techniques. Molecular imaging can be used to
      explore many of the hallmarks of cancer biology, including angiogenesis,
      proliferation, tissue invasion, evasion of apoptosis, and self-sufficiency in
      growth signals. Since many of these aspects of cancer biology are in turn the
      targets of novel therapies in development, molecular imaging techniques have
      great potential to inform trials of these new agents. The high cost of clinical
      drug development mandates the optimisation of early phase trial design to
      maximise the collection of evidence for efficacy and proof of mechanism,
      endpoints which have, in a number of examples, already been provided by molecular
      imaging. The variety provided by novel chemistry, and the availability of
      isotopes with varying physical properties, particularly suits PET imaging as a
      functional modality for application in clinical trials.

PMID- 19768640
TI  - An economic evaluation of budesonide/formoterol for maintenance and reliever
      treatment in asthma in general practice.
AB  - INTRODUCTION: In budesonide/formoterol (Symbicort(R) Turbuhaler(R), AstraZeneca,
      Lund, Sweden) maintenance and reliever therapy (SMART), patients with asthma take
      a daily maintenance dose of budesonide/formoterol, with the option of taking
      additional doses for symptom relief instead of a short-acting beta(2)-agonist
      (SABA). This study assesses the cost-effectiveness of SMART compared with usual
      care in patients with mild-to-moderate persistent asthma treated by general
      practitioners in the Netherlands from a societal perspective. METHODS: The study
      was linked to a randomized, active-controlled, open-label, multicenter, 12-month
      clinical trial, with a prospective collection of resource use. One hundred and
      two patients > or =18 years with mild-to-moderate persistent asthma and daily
      inhaled corticosteroids (ICS) prior to the trial were included. SMART was given
      as two inhalations of budesonide/formoterol (100/6 microg) once daily, plus
      additional doses as needed. The control group was treated according to
      guidelines, which prescribe medium daily doses of ICS plus an SABA if needed. A
      long-acting beta(2)-agonist (LABA) is added if necessary. Effectiveness was
      measured as the proportion of asthma-control days, Asthma Control Questionnaire
      (ACQ) scores, the net proportion of patients with relevant ACQ improvement, and
      the proportion of well-controlled patients. Costs included asthma medication,
      physician contacts, and absence from work. RESULTS: Mean total costs for SMART
      were <euro>134.81 lower (95% CI: -<euro>439.48; <euro>44.85). Production losses
      were <euro>94.10 (95% CI: -<euro>300.60; <euro>0.29) lower for SMART (<euro>10.77
      vs. <euro>104.87). No significant differences in health outcomes were seen, with
      3.81 fewer asthma-control days per patient-year for SMART (95% CI: -36.8; 30.8),
      a 0.049 better ACQ score (95% CI: -0.21; 0.29), a 5.8% larger net proportion of
      improved patients (95% CI: t15.6%; 27.3%), and a 2.1% (95% CI: -25.5; 20.8%)
      smaller increase in the proportion of well-controlled patients. CONCLUSIONS:
      Treating primary care patients with mild-to-moderate persistent asthma with SMART
      instead of ICS plus bronchodilators does not affect health outcomes and does not
      increase costs; therefore, is likely to be an alternative for guideline-directed
      treatment, from a health and economic perspective.

PMID- 19768641
TI  - Improving patient acceptance and adherence in diabetes management: a focus on
      insulin therapy.
AB  - Maintaining tight glycemic control is an important issue for patients with type 2
      diabetes. Empowering patients to be actively involved in the management of their
      diabetes can improve glycemic control through education, communication, and the
      use of patient-friendly insulin regimens. The primary care physician plays an
      important role in helping patients manage their disease by encouraging initiation
      of treatment with insulin analogs, which are more convenient, more predictable,
      and better tolerated than traditional human insulin therapies. Modern insulin
      delivery devices, such as insulin pens, may also help improve patient acceptance
      of insulin therapy.

PMID- 19768642
TI  - Photostability and phytotoxicity of selected sunscreen agents and their
      degradation mixtures in water.
AB  - The study on the photostability of six UV filters in aqueous solution was
      combined with investigations on the phytotoxicity of the produced degradation
      mixtures. During the exposure to artificial sunlight over 72 h, the degradation
      of three of the UV filters evaluated was observed with half-lives between 20 and
      59 h. The structural changes of iso-amylmethoxy-cinnamate (IAMC), ethylhexyl
      methoxy-cinnamate (EHMC), and 4-methylbenzyliden camphor (4-MBC) occurred during
      irradiation were consistent with isomerisation and polymerization (IAMC and EHMC)
      whereas 2-ethylhexyl-4-(dimethylamino)benzoate (OD-PABA) was degraded. The
      analysis of the UV filters and their degradation products was performed by stir
      bar sorptive extraction (SBSE) followed by thermodesorption-gas chromatography
      mass spectrometry (TD-GC-MS) or liquid desorption-liquid chromatography-mass
      spectrometry (LD-LC-MS). The phytotoxicological potential of the UV filters was
      examined in vitro by evaluating reproduction inhibition of the chlorophyte
      microalgae Scenedesmus vacuolatus. Excess toxicity was calculated by comparing
      experimental derived median efficiencies after log-logistic modeling to predict
      effects assuming narcotic mode of action. Benzophenone-3 (BP-3) showed 43-fold
      higher toxicity than theoretically predicted and a more specific mode of action
      was assumed. The other UV filters tested indicated toxicity in the range of
      modeled narcosis. For IAMC, EHMC, and OD-PABA the phytotoxicity of their
      photodegradation mixtures was followed over time. Phytotoxicity decreased
      directly with the reduction of the parent substance from the solution. Five of
      the tested UV filters do not represent a risk at least for algae. Octocrylen and
      4-MBC were found to be photostable but few toxic to algae. EHMC, IAMC, and OD
      PABA were fast degraded during UV radiation and the phytotoxicity of the
      corresponding degradation mixtures was low and decreased onward during exposure.
      Thus, for the UV filters studied, it could be confirmed that sunlight can account
      noticeably for decontamination and detoxification of contaminated water. However,
      due to its potential accumulation in combination with a specific mode of action,
      BP-3 may imply probable environmental risks at least to algae. This study
      emphasizes the need of a combined chemical and toxicological evaluation for a
      reliable risk assessment concerning degradation processes exemplified here for UV
      protecting agents.

PMID- 19768643
TI  - Detoxification of mercury species--an in vitro study with antidotes in human
      whole blood.
AB  - To investigate the effects of mercury species intoxication and to test the
      efficiency of different commonly applied antidotes, human whole blood and plasma
      surrogate samples were spiked with inorganic mercury (Hg2+) and methylmercury
      (MeHg+, CH3Hg+) prior to treatment with the antidotes 2,3-dimercaptopropan-1-ol
      (British Anti Lewisite), 2,3-dimercaptosuccinic acid (DMSA), and N-acetylcysteine
      (NAC). For mercury speciation analysis in these samples, liquid chromatography
      was coupled to either inductively coupled plasma mass spectrometry (ICP-MS) or
      electrospray ionisation time-of-flight mass spectrometry (ESI-TOF-MS). Adduct
      formation between mercury species and physiological thiols (cysteine and
      glutathione) was observed as well as the release of glutathione under treatment
      with the antidotes DMSA and NAC.

PMID- 19768644
TI  - Early experience with percutaneous cryoablation of extra-abdominal desmoid
      tumors.
AB  - OBJECTIVE: Surgical resection, radiation therapy and chemotherapy are all
      accepted as standard treatments for extra-abdominal desmoid (EAD) tumors, but
      their effectiveness has been limited by frequent local recurrence. The purpose of
      this article is to describe our early experiences with using percutaneous
      cryoablation for local control of extra-abdominal desmoid tumors in five patients
      whose tumors had failed to respond to standard therapy. MATERIAL AND METHODS: In
      a retrospective search of our institution's radiology database for patients who
      had undergone percutaneous cryoablation for treatment of EAD tumors between June
      2004 and July 2007, we identified five patients (three female and two male). No
      patients were excluded from this review. Three of these patients had been
      referred for cryoablation for local tumor control, and two had been referred for
      palliation of inoperable tumors. The age range of the patients at the time of
      cryoablation was 9-41 years. The treated EAD tumors were located in the neck,
      shoulders and trunk and ranged in size from 3.0 cm to 10.0 cm. Medical records
      were reviewed for short-term and long-term follow-up, and patients were contacted
      for additional follow-up. Patients were asked to rate their pain as absent, mild,
      moderate or severe, and to compare it with their levels before cryoablation,
      describing it as improved, unchanged or worsened. Radiology records were reviewed
      to follow the size of the EAD tumors before and after cryotherapy. RESULTS: For
      the three patients referred for local control of EAD tumors, complete tumor
      coverage with the ablation zones was achieved. Two of these patients, with masses
      3.0 cm and 4.9 cm in diameter, reported complete absence of pain at both short
      term and long-term follow-up at 13 months and 49 months. Their tumors had
      completely resolved on long-term imaging follow-up at 19 months and 43 months.
      The third patient, with a 6.1 cm mass, reported improved mild pain at 6 months,
      and imaging showed a moderate decrease of tumor size. For the two patients
      referred for palliative therapy, initial partial pain relief was felt 2 weeks
      after the procedure, At long-term (58 months) follow-up of one patient with a 9.1
      cm mass, the tumor was still present although reduced in size, and local pain had
      returned to its former moderate level. In the other patient who underwent only
      partial treatment of a 10.0 cm mass, at long-term follow-up (36 months) the mass
      had enlarged and pain had returned to the pretreatment, moderate level.
      CONCLUSION: Cryoablation appears to be an effective alternative treatment for the
      achievement of local control of small and moderately sized EAD tumors, but it is
      likely of limited use in patients with larger tumors that have untreatable
      regions due to involvement of vital structures. Continued research evaluating
      cryoablation for the treatment of EAD tumors is needed.

PMID- 19768645
TI  - LEOPARD syndrome with recurrent PTPN11 mutation Y279C and different cutaneous
      manifestations: two case reports and a review of the literature.
AB  - LEOPARD syndrome (LS) is a heterogeneous disease characterised mainly by
      cutaneous manifestations. LEOPARD is the acronym for its major features-multiple
      lentigines, electrocardiographic conduction defects, ocular hypertelorism,
      pulmonary stenosis, abnormalities of (male) genitalia, retardation of growth and
      sensorineural deafness. As clinical manifestations are variable, molecular
      testing is supportive in the diagnosis of LS. We describe two unrelated LS cases
      with a common PTPN11 mutation Y279C and with completely different clinical
      features including distinct changes in skin pigmentation. In patient 1, the first
      complaint was hyperactive behaviour. First lentigines were presented at birth,
      but intensive growth began at the age of 2-4 years. Multiple dark lentigines were
      located mainly on the face and the upper part of the trunk, but the oral mucosa
      was spared. Patient 2 was born from induced labour due to polyhydramnion, and in
      the second week of life, mitral valve insufficiency and hypertrophic
      cardiomyopathy were diagnosed. Rapid growth of lentigines began at the age of 3
      years. These are mostly located in the joint areas in the lower extremities; the
      face and upper trunk are spared from lentigines. In both cases, the rapid growth
      of lentigines made it possible to shift the diagnosis towards LS. Clinicians
      should give more consideration to rare genetic syndromes, especially in the case
      of symptoms from different clinical areas.

PMID- 19768646
TI  - Cauda equina lesions as a complication of spinal surgery.
AB  - Although the most common aetiology of cauda equina lesions is lumbar
      intervertebral disc herniation, iatrogenic lesions may also be the cause. The aim
      of this study was to identify and present patients in whom cauda equina lesions
      occurred after spinal surgery. From the author's series of patients with cauda
      equina lesions, those with the appearance of sacral symptoms after spinal surgery
      were identified. To demonstrate lesions more objectively, electrodiagnostic
      studies were performed in addition to history and clinical examination. Imaging
      studies were also reviewed. Of 69 patients from the series, 11 patients in whom a
      cauda equina lesion developed after spinal surgery were identified. The aetiology
      comprised surgery for herniated intervertebral disc in 5 (4 performed by a single
      surgeon), spinal stenosis surgery in 4, and postoperative lumbar epidural
      haematoma in 2 patients (each performed by a different surgeon). Proportion of
      spinal surgeries with this complication varied from 0 to 6.6 per thousand in
      different centres. Patients with iatrogenic cauda equina lesion were
      significantly older (p < 0.001), and reported more severe urinary, but similar
      bowel and sexual symptoms compared to other patients in the series. In conclusion
      the study identified spinal surgery as the cause of approximately 15% of cauda
      equina lesions. More than a third of lesions developed after procedures performed
      by a single surgeon. Most of the remaining lesions could probably be avoided by
      better surgical technique (e.g. the use of a high-speed drill instead of a
      Kerrison rongeur in patients with severe spinal stenosis), or prevented by closer
      postoperative monitoring (e.g. in patients with postoperative lumbar epidural
      haematoma).

PMID- 19768647
TI  - Do rufous hummingbirds (Selasphorus rufus) use visual beacons?
AB  - Animals are often assumed to use highly conspicuous features of a goal to head
      directly to that goal ('beaconing'). In the field it is generally assumed that
      flowers serve as beacons to guide pollinators. Artificial hummingbird feeders are
      coloured red to serve a similar function. However, anecdotal reports suggest that
      hummingbirds return to feeder locations in the absence of the feeder (and thus
      the beacon). Here we test these reports for the first time in the field, using
      the natural territories of hummingbirds and manipulating flowers on a scale that
      is ecologically relevant to the birds. We compared the predictions from two
      distinct hypotheses as to how hummingbirds might use the visual features of
      rewards: the distant beacon hypothesis and the local cue hypothesis. In two field
      experiments, we found no evidence that rufous hummingbirds used a distant visual
      beacon to guide them to a rewarded location. In no case did birds abandon their
      approach to the goal location from a distance; rather they demonstrated
      remarkable accuracy of navigation by approaching to within about 70 cm of a
      rewarded flower's original location. Proximity varied depending on the size of
      the training flower: birds flew closer to a previously rewarded location if it
      had been previously signalled with a small beacon. Additionally, when provided
      with a beacon at a new location, birds did not fly directly to the new beacon.
      Taken together, we believe these data demonstrate that these hummingbirds depend
      little on visual characteristics to beacon to rewarded locations, but rather that
      they encode surrounding landmarks in order to reach the goal and then use the
      visual features of the goal as confirmation that they have arrived at the correct
      location.

PMID- 19768648
TI  - Expression, purification, and characterization of the humoral immune response to
      recombinant MyfA protein of Yersinia enterocolitica.

PMID- 19768649
TI  - Fosfomycin in a single dose versus a 7-day course of amoxicillin-clavulanate for
      the treatment of asymptomatic bacteriuria during pregnancy.
AB  - The purpose of this paper was to compare the efficacy of a single dose of 3 g of
      fosfomycin to that of a 7-day regimen of amoxicillin-clavulanate in the treatment
      of asymptomatic bacteriuria during pregnancy. A randomised, prospective,
      interventional, analytical, longitudinal study was undertaken, in which the
      efficacy of two antibiotic regimens (one short and the other long) in the
      treatment of pregnant women with asymptomatic bacteriuria is compared. One
      hundred and nine patients were randomly assigned to two groups: 56 were treated
      with amoxicillin-clavulanate and 53 with fosfomycin. The two groups were similar
      in terms of co-morbidity, treatments received during pregnancy, obstetric,
      gynaecological and surgical history and laboratory data. The efficacy of the two
      regimens was similar and the eradication rate was over 80% in both groups (P =
      0.720) (relative risk [RR] 1.195, 95% confidence interval [CI]: 0.451-3.165). The
      number of reinfections was greater in the amoxicillin-clavulanate group (P =
      0.045). The secondary effects were lower in the fosfomycin group (P = 0.008).
      There were no significant differences in the number of persistences (P = 0.39),
      development of symptomatic urinary infections (P = 0.319) or recurrences (P =
      0.96). Treatment with a single dose of fosfomycin is as effective as the standard
      course of treatment with amoxicillin-clavulanate and may be preferable due to its
      simpler administration and the smaller number of reinfections.

PMID- 19768650
TI  - Molecular characterization and experimental host range of an isolate of Wissadula
      golden mosaic St. Thomas virus.
AB  - Partial genome segments of a begomovirus were previously amplified from Wissadula
      amplissima exhibiting yellow-mosaic and leaf-curl symptoms in the parish of St.
      Thomas, Jamaica and this isolate assigned to a tentative begomovirus species,
      Wissadula golden mosaic St. Thomas virus. To clone the complete genome of this
      isolate of Wissadula golden mosaic St. Thomas virus, abutting primers were
      designed to PCR amplify its full-length DNA-A and DNA-B components. Sequence
      analysis of the complete begomovirus genome obtained, confirmed that it belongs
      to a distinct begomovirus species and this isolate was named Wissadula golden
      mosaic St. Thomas virus-[Jamaica:Albion:2005] (WGMSTV-[JM:Alb:05]). The genome of
      WGMSTV-[JM:Alb:05] is organized similar to that of other bipartite Western
      Hemisphere begomoviruses. Phylogenetic analyses placed the genome components of
      WGMSTV-[JM:Alb:05] in the Abutilon mosaic virus clade and showed that the DNA-A
      component is most closely related to four begomovirus species from Cuba, Tobacco
      leaf curl Cuba virus, Tobacco leaf rugose virus, Tobacco mottle leaf curl virus,
      and Tomato yellow distortion leaf virus. The putative Rep-binding-site motif in
      the common region of WGMSTV-[JM:Alb:05] was observed to be identical to that of
      Chino del tomate virus-Tomato [Mexico:Sinaloa:1983], Sida yellow mosaic Yucatan
      virus-[Mexico:Yucatan:2005], and Tomato leaf curl Sinaloa virus-[Nicaragua:Santa
      Lucia], suggesting that WGMSTV-[JM:Alb:05] is capable of forming viable pseudo
      recombinants with these begomoviruses, but not with other members of the Abutilon
      mosaic virus clade. Biolistic inoculation of test plant species with partial
      dimers of the WGMSTV-[JM:Alb:05] DNA-A and DNA-B components showed that the virus
      was infectious to Nicotiana benthamiana and W. amplissima and the cultivated
      species Phaseolus vulgaris (kidney bean) and Lycopersicon esculentum (tomato).
      Infected W. amplissima plants developed symptoms similar to symptoms observed
      under field conditions, confirming that this virus is a causal agent of Wissadula
      yellow mosaic disease in W. amplissima.

PMID- 19768651
TI  - Health states of women after conservative surgery and radiation for breast
      cancer.
AB  - The aim of the study is to use the EQ-5D instrument to evaluate the long-term
      health states of women with early stage breast cancer treated by breast
      conserving surgery and radiation. A total of 1,050 women treated with
      conservative surgery and radiation with or without systemic therapy completed
      2,480 questionnaires during follow-up visits. The EQ-5D is a standardized and
      validated instrument for measuring quality of life outcomes. The descriptive
      system uses 5 dimensions of health with three possible levels of response that
      combine into 243 (3(5)) possible unique health states that are each assigned a
      values-based index score from 0 to 1. The visual analog scale (VAS) rates health
      on a simple vertical line from 0 to 100. Higher scores correspond to better
      health status. The mean index scores were 0.89 (95% CI: 0.87-0.91) at 5 years,
      0.9 (95% CI: 0.86-0.94) at 10 years, and 0.9 (95% CI: 0.83-1.0) at 15 years.
      There were no significant differences in health states between patients by age
      when compared with U.S. controls. There was a statistically significant positive
      correlation between the results of the VAS and descriptive system. Significant
      trends in health dimensions over 15 years were increased problems with self-care
      and decreased problems with anxiety/depression, pain/discomfort, and performing
      usual activities. This study of EQ-5D is unique and demonstrates very high
      quality of life in patients long-term after breast-conserving surgery and
      radiation. These health states are comparable to the adult female U.S.
      population. These data will provide valuable patient utility information for
      informing decision analyses investigating new treatments in women with breast
      cancer.

PMID- 19768652
TI  - Community treatment for problem gambling: sex differences in outcome and process.
AB  - This study compared sex differences in related treatment outcomes and processes
      in a community sample of outpatient problem gambling treatment-seekers.
      Participants attended approximately seven sessions of cognitive-behavioral
      treatment. Women were more likely to have a history of psychiatric comorbidity,
      prefer non-strategic/non-skill forms of gambling, and have a more rapid
      progression towards a gambling problem than did men. At the 6-month post
      treatment follow-up, men were found to have improved to a significantly greater
      degree on measures of gambling severity and rates of abstinence in comparison to
      women. Moreover, men rated treatment components to be more helpful, whereas women
      found specific gambling-related treatment interventions (e.g., identification of
      high-risk situations, gambling beliefs and attitudes) to be less helpful.
      Implications for identifying treatment needs of women seeking problem gambling
      treatment are discussed.

PMID- 19768653
TI  - Secondary disorders of glycosylation in inborn errors of fructose metabolism.
AB  - Adamowicz and colleagues raised the alert in 2007 about patients with atypical
      hereditary fructose intolerance (HFI) primarily misdiagnosed as CDG Ix. We
      describe a girl with neonatal hypertonia, facial trismus, absent swallowing and
      coughing reflexes, gastro-oesophageal reflux and sporadically elevated Krebs
      cycle metabolites and lactate. At 14 months microcephaly and hepatomegaly were
      noted, with hypertransaminasaemia but normal blood coagulation, glucose,
      phosphate, and absent urinary reducing substances. Neurological impairment
      persisted. Because of hepatic and neurological abnormalities with developmental
      delay, Tf IEF was performed and showed a severe type 1 pattern, resulting in a
      wrong diagnosis of CDG. Subsequently, an aversion to fruits suggested HFI,
      confirmed by the finding of ALDOB mutations (p.A150P/p.N335K). The girl improved
      with fructose-free diet, but liver cirrhosis led to hepatic transplantation. She
      is now 7 years old with good evolution; facial trismus and hypertonia reversed,
      but microcephaly persists. Transferrin MALDI-TOF MS characterization revealed
      underoccupation of glycosylation sites and glycan abnormalities, which reversed
      with dietary treatment. High maternal fructose concentrations might have caused
      neonatal abnormalities. Although in our patient's mother there is no fructose
      accumulation at present, it is possible that increased ingestion of fruits and
      vegetables during pregnancy, together with her heterozygosity, caused an
      accumulation of fructose that finally affected the fetus. We also describe
      slightly abnormal transferrin isoelectric focusing and MALDI-TOF MS patterns of
      intact transferrin and N-glycans in a fructose-1,6-bisphosphatase (FBP1)
      deficient patient. While HFI is a well-known cause of secondary CDG, we found no
      reports of abnormal transferrin isoelectric focusing patterns in FBP1 deficiency
      and we introduce this condition as a possible secondary cause for altered
      transferrin isoelectric focusing.

PMID- 19768654
TI  - Effects of integrins on laminin chemotaxis by hepatocellular carcinoma cells.
AB  - To quantitatively evaluate the effects of integrins alpha1beta1, alpha2beta1,
      alpha3beta1, alpha4beta1, alpha5beta1, and alpha6beta1 on the chemotaxis of
      hepatocelluar carcinoma (HCC) cell line SMMC-7721 to laminin (LN). A modified
      dual-micropipette system was used to dynamically and quantitatively monitor the
      formation of pseudopod protrusion of HCC cells toward LN in the presence or
      absence of specific antibodies against integrins alpha1, alpha2, alpha3, alpha4,
      alpha5, alpha6, and beta1. Additionally, the expression levels of different
      integrin subunits on the surface of the cells were determined via flow cytometry
      analysis. In response to equal concentrations of LN in both micropipettes, HCC
      cells form symmetrical pseudopod protrusions on both sides. Addition of
      antibodies against alpha3, alpha6, or beta1 into one micropipette leads to
      significant reduction of pseudopod formation on that side, while antibodies
      against alpha1, alpha2, alpha4, and alpha5 do not affect the symmetrical
      formation of pseudopods in either micropipette. The percentages of HCC cells
      positive for expression of integrins alpha1, alpha2, alpha3, alpha4, alpha5,
      alpha6, and beta1 were 95.07, 23.17, 95.55, 2.47, 34, 14.29, and 95.78%,
      respectively. Integrins alpha3beta1 and alpha6beta1 are important cell surface
      receptors that mediate the chemotaxis of HCC cells toward LN.

PMID- 19768655
TI  - The Maastricht social participation profile: development and clinimetric
      properties in older adults with a chronic physical illness.
AB  - PURPOSE: To develop and test the Maastricht Social Participation Profile (MSPP),
      an instrument measuring the actual social participation by older adults with a
      chronic physical illness, in accordance with their own definition of social
      participation. METHODS: The development process consisted of a number of steps,
      ending with a field test in two waves (n = 412 and n = 125) among a random sample
      of people older than 59 years with either COPD or diabetes mellitus.
      Reproducibility was evaluated with intraclass correlation coefficients (ICCs) and
      smallest real differences at group level (SRDs(group)). Convergent and
      discriminant validity were evaluated with Pearson correlation coefficients
      between the MSPP and the Frenchay Activities Index (FAI). RESULTS: The MSPP
      consists of four indices: consumptive participation, formal social participation,
      informal social participation-acquaintances and informal social participation
      family. Each index measured diversity and frequency of participation. ICCs ranged
      between 0.63 and 0.83. SRDs(group) ranged between 0.05 and 0.09. Convergent and
      discriminant validity were supported by the correlations between the
      MSPP(frequency) and the FAI. CONCLUSIONS: The MSPP has good validity and
      acceptable reproducibility. Its distinguishing features are its focus on actual
      social participation and the possibility to calculate both diversity and
      frequency scores.

PMID- 19768656
TI  - Extracorporeal membrane oxygenation in adults with severe respiratory failure: a
      multi-center database.
AB  - OBJECTIVE: To evaluate clinical and treatment factors for patients recorded in
      the Extracorporeal Life Support Organization (ELSO) registry and survival of
      adult extracorporeal membrane oxygenation (ECMO) respiratory failure patients.
      DESIGN AND PATIENTS: Retrospective case review of the ELSO registry from 1986
      2006. Data were analyzed separately for the entire time period and the most
      recent years (2002-2006). RESULTS: Of 1,473 patients, 50% survived to discharge.
      Median age was 34 years. Most patients (78%) were supported with venovenous ECMO.
      In a multi-variate logistic regression model, pre-ECMO factors including
      increasing age, decreased weight, days on mechanical ventilation before ECMO,
      arterial blood pH <or= 7.18, and Hispanic and Asian race compared to white race
      were associated with increased odds of death. For the most recent years (n =
      600), age and PaCO(2) >or= 70 compared to PaCO(2) <or= 44 were also associated
      with increased odds of death. The two diagnostic categories acute respiratory
      failure and asthma compared to ARDS were associated with decreased odds of
      mortality as was venovenous compared to venoarterial mode. CPR and complications
      while on ECMO including circuit rupture, central nervous system infarction or
      hemorrhage, gastrointestinal or pulmonary hemorrhage, and arterial blood pH < 7.2
      or >7.6 were associated with increased odds of death. CONCLUSIONS: Survival among
      this cohort of adults with severe respiratory failure supported with ECMO was
      50%. Advanced patient age, increased pre-ECMO ventilation duration, diagnosis
      category and complications while on ECMO were associated with mortality.
      Prospective studies are needed to evaluate the role of this complex support mode.

PMID- 19768657
TI  - Lack of specific gray matter alterations in restless legs syndrome in elderly
      subjects.
AB  - Magnetic resonance imaging studies using voxel-based morphometry (VBM) have been
      inconsistent in demonstrating volumetric differences in patients with restless
      legs syndrome (RLS). Since treatment, age and selection of patients may introduce
      a methodological bias, we conducted optimized VBM analyses in unmedicated elderly
      subjects reporting RLS. Two hundred-four voluntaries, 65.9 +/- 0.6 year-old, free
      of any significant medical condition and without previous neurological or
      psychiatric medication, participated at the study. After exclusion of subjects
      having sleep-related breathing disorders and previous silent infarct, 71
      subjects, 54 without RLS (RLS-) and 17 having RLS (RLS+) were analyzed. No
      structural change in gray matter density was found in RLS+ subjects compared to
      RLS- subjects. Subjects with RLS+ symptoms showed a small gray matter volume in
      the left occipital region without, however, statistical significance. VBM
      analysis did not show any significant change in subcortical and cortical gray
      matter in unmedicated elderly subjects with RLS symptoms. These results confirm
      the lack of specificity of thalamic and subcortical changes in restless legs
      syndrome.

PMID- 19768658
TI  - A phase II prospective study of sequential myeloablative chemotherapy with
      hematopoietic stem cell rescue for the treatment of selected high risk and
      recurrent central nervous system tumors.
AB  - High risk/recurrent CNS tumors have a poor prognosis. We studied tandem high dose
      chemotherapy (HDC) with hematopoietic progenitor stem cell rescues (HPCR) as
      potentially curative therapy. Twenty-four patients (mean age 6.8 years) were
      enrolled, 19 underwent HDC/HPCR. Diagnoses were medulloblastoma (n = 9), germ
      cell tumor (n = 4), high grade astrocytoma (n = 2), supratentorial PNET (n = 1),
      pineoblastoma (n = 2), or papillary meningioma (n = 1). Cytoreduction regimen #1
      consisted of carboplatin (500 mg/m(2)) x 3 days, etoposide (250 mg/m(2)) x 3
      days, and thiotepa (300 mg/m(2)) x 3 days. Patients without progression or
      excessive toxicity (n = 11), received regimen #2 with melphalan (60 mg/m(2)) x 3
      days and cyclophosphamide (1,500 mg/m(2)) x 4 days. Projected overall/event-free
      survival for the 19 patients was 51/37% and 34/28% at 1 and 5 years,
      respectively. Toxicity was significant with six treatment related deaths
      including four with veno-occlusive disease. This regimen of sequential HDC/HPCR
      in high risk/recurrent CNS tumor patients is not feasible due to toxicity.

PMID- 19768659
TI  - In vivo evaluation of intracellular drug-nanocarriers infused into intracranial
      tumours by convection-enhanced delivery: distribution and radiosensitisation
      efficacy.
AB  - The objective of the present study was to investigate the interest of convection
      enhanced delivery (CED) for the administration of a nanocarrier-based
      radiosensitizing chemotherapy in the rat brain. Pursuing on newly developed lipid
      nanocapsules (LNC) that can be internalised within brain tumour cells, we studied
      their intracerebral distribution when labelled with fluorescent Nile red (NR). As
      paclitaxel (Px) represents an interesting radiosensitiser, we also evaluated the
      potential radiosensitising effects of Px-loaded LNC administered through CED in
      the 9L intracranial rat glioblastoma model. The distribution study demonstrated
      that CED injection of NR-loaded LNC (NR-LNC) improved significantly the volume of
      distribution of NR when matched with simple injection (by about 150 fold). It
      also reveals that the LNC perfusion of a whole tumour forming area inside the CNS
      (6 days after implantation of 10(3) 9L cells) is achievable through CED
      injection, whilst preserving the ability of LNC to reach the intracellular space
      of encountered tumour cells. Having established an animal model of encephalic
      irradiation close to the clinic (18 Gray in three fractions of six Gray at days
      8, 11 and 14 after 9L cell implantation) we proved the feasibility of the
      combination of CED for the administration of drug-loaded LNC with external beam
      therapy. Although a single CED injection of Px-LNC at low Px dose (375 mug/kg of
      bodyweight) gave the best median survival (twice that of untreated controls), it
      underlines the need for optimisation. Hence, the possibility of grafting
      recognition moieties onto the LNC surface combined to their biocompatibility must
      be beneficial.

PMID- 19768660
TI  - Motivators for resolving or seeking help for gambling problems: a review of the
      empirical literature.
AB  - This literature review summarizes recent empirical research on the reasons
      disordered gamblers try, through treatment or otherwise, to resolve or reduce
      their gambling problems. Relevant databases and bibliographies were searched for
      English-language studies, published since 1998, that asked gamblers themselves
      about motivators for action. Found were ten studies addressing reasons for trying
      to resolve or reduce gambling problems, five addressing reasons for seeking help
      and four addressing reasons for requesting self-exclusion from casinos. Help
      seeking occurred largely in response to gambling-related harms (especially
      financial problems, relationship issues and negative emotions) that had already
      happened or that were imminent. Resolution was often motivated by the same kinds
      of harms but evaluation/decision-making and changes in lifestyle or environment
      played a more prominent role. Self-exclusion was motivated by harms,
      evaluation/decision-making and a wish to regain control. Awareness and
      educational materials could incorporate messages that might encourage heavy
      gamblers to make changes before harms became too great. Intervention development
      could also benefit from more research on the motivators leading to successful
      (vs. failed) resolution, as well as on the ways in which disordered gamblers are
      able to overcome specific barriers to seeking help or reaching resolution.

PMID- 19768661
TI  - Elevated zinc induces endothelial apoptosis via disruption of glutathione
      metabolism: role of the ADP translocator.
AB  - Zinc is the second-most abundant transition metal within cells and an essential
      micronutrient. Although adequate zinc is essential for cellular function,
      intracellular free zinc (Zn(2+)) is tightly controlled, as sustained increases in
      free Zn(2+) levels can directly contribute to apoptotic endothelial cell death.
      Moreover, exposure of endothelial cells to acute nitrosative and/or oxidative
      stress induces a rapid rise of Zn(2+) with mitochondrial dysfunction and the
      initiation of apoptosis. This apoptotic induction can be mimicked through
      addition of exogenous ZnCl(2) and mitigated by zinc-chelation strategies,
      indicating Zn(2+)-dependent mechanisms in this process. However, the molecular
      mechanisms of Zn(2+)-mediated mitochondrial dysfunction are unknown. Here we
      report that free Zn(2+) disrupts cellular redox status through inhibition of
      glutathione reductase, and induces apoptosis by redox-mediated inhibition of the
      mitochondrial adenine nucleotide transporter (ANT). Inhibition of ANT causes
      increased mitochondrial oxidation, loss of ADP uptake, mitochondrial
      translocation of bax, and apoptosis. Interestingly, pre-incubation with
      glutathione ethyl ester protects endothelial cells from these observed effects.
      We conclude that key mechanisms of Zn(2+)-mediated apoptotic induction include
      disruption of cellular glutathione homeostasis leading to ANT inhibition and
      decreases in mitochondrial ATP synthesis. These pathways could represent novel
      therapeutic targets during acute oxidative or nitrosative stress in cells and
      tissues.

PMID- 19768662
TI  - Osteoblasts modulate Ca2+ signaling in bone-metastatic prostate and breast cancer
      cells.
AB  - Metastatic prostate and breast cancers display a predilection for the skeleton.
      The high incidence of skeletal metastasis may be a reflection of favorable
      reciprocal interactions between the bone microenvironment and disseminated cancer
      cells. Here we show that bone-metastatic PC3-ML prostate cancer cells and MDA-231
      breast cancer cells-when co-cultured with human osteoblasts-down-regulate the
      increase in cytosolic free calcium (Ca(2+)) induced by agonist stimulation. This
      osteoblast promoted alteration of Ca(2+) signaling develops and reverts in a time
      dependent manner. Most importantly, the Ca(2+) responses of cancer cells lacking
      bone metastatic potential are not affected by osteoblasts. The limited increase
      in cytosolic Ca(2+) observed in bone-metastatic cells does not result from
      depleted intracellular Ca(2+) stores but rather a decreased entry of Ca(2+) from
      the extracellular space. Interestingly, the inhibition of histone deacetylase in
      cancer cells replicates the changes in Ca(2+) signaling induced by osteoblasts,
      suggesting the participation of epigenetic mechanisms. Finally, cancer cells
      harvested from skeletal metastases induced in mice showed Ca(2+) responses
      identical to cells co-cultured with osteoblasts. However, Ca(2+) signaling in
      cancer cells recovered from metastases to soft-tissues was not affected,
      emphasizing the role of the bone microenvironment in regulating the functional
      behavior of bone-metastatic cells. We propose that osteoblasts protect selected
      malignant phenotypes from cell death caused by an excessive increase in cytosolic
      Ca(2+), thereby facilitating their progression into macroscopic skeletal
      metastases.

PMID- 19768663
TI  - Chemical and mineralogical characterization on glazes of ceramics from Coimbra
      (Portugal) from the sixteenth to nineteenth centuries.
AB  - Chemical, mineralogical and textural characterizations were performed on glazed
      pieces prepared in laboratory as well as on faiences fragments collected from the
      existing remains in "Santa Clara-a-Velha" monastery (Coimbra, Portugal). The
      chemical investigation was carried out using micro X-ray fluorescence (micro
      EDXRF) and wavelength dispersive X-ray fluorescence (WDXRF); the mineralogical
      results using X-ray diffraction (XRD) and the textural profile was obtained by
      scanning electron microscopy coupled with an energy dispersive spectroscopy
      system (SEM-EDS). Attention has been drawn to the glaze mineralogical changes
      during the firing temperature process, where three different types of glazes were
      submitted to three different firing temperatures (800 degrees C, 900 degrees C
      and 1,000 degrees C). Under these conditions, it is possible to relate the
      mineralogical content of the fragments to their firing temperature. Furthermore,
      we focused our purposes on identifying the technological aspects of the ceramic
      production in Coimbra, such as the raw materials, manufacture techniques and
      firing temperature adopted for the glaze. The latter aspect is highly dependent
      on the ceramic materials. In the framework of a more general project, this survey
      has as premise the recognition of a pattern, which is thought to be exclusively
      typical from the region of Coimbra. The perspective developed in the present work
      is towards reliable archaeometric criteria, which can be used to characterise
      scientifically the ceramics from Coimbra.

PMID- 19768664
TI  - Backbone and side-chain (1)H, (13)C and (15)N resonance assignments of LEN, a
      human immunoglobulin kappaIV light-chain variable domain.
AB  - (1)H, (13)C and (15)N resonance assignments are presented for a recombinant 114
      amino acid human immunoglobulin (Ig) kappaIV light-chain variable domain (VL)
      LEN, which displays a high degree of sequence identity with another human Ig
      kappaIV VL, SMA. While SMA is highly amyloidogenic in vivo and in vitro and has
      been linked to the pathogenesis of light-chain amyloidosis, LEN is non
      amyloidogenic in vivo and can be converted to the amyloid state only in vitro
      under destabilizing conditions. Measurements of longitudinal and transverse amide
      (15)N relaxation rates confirm that, as expected, LEN is a dimer at physiological
      pH and typical concentrations used for NMR studies, and the analysis of secondary
      chemical shifts indicates that the protein has a high beta-sheet content. These
      findings are consistent with previously published biophysical data and the high
      resolution X-ray structure of LEN.

PMID- 19768665
TI  - [New data on occupational exposure to isocyanates].
AB  - During recent decades the industrial use of isocyanates has expanded enormously
      due to the huge product palette with a variety of different properties. As
      opposed to the fast technical development, there is a delay in the formulation of
      respective occupational health and safety regulations. Adverse health effects of
      isocyanates are mainly due to inhalative exposure. In addition, cutaneous contact
      causes toxic as well as allergic reactions. Oligomeric and polymeric isocyanates
      that are mostly used in the industry are only regulated in the Technical Rules
      for Hazardous Substances 430 (TRGS 430), but not by the mandatory occupational
      medical surveillance directive (Arbeitsmedizinische Vorsorgeverordnung). Although
      the TRGS 430 facilitates risk assessment (e. g., the aerosol penetration factor
      is related to the size of aerosols; only the acute irritative effect of
      oligomeric and polymeric isocyanates as shown in animal studies is taken into
      consideration in the case of defining a so-called evaluation factor), so far this
      new regulation has not yet been implemented in practice according to our own
      findings.

PMID- 19768666
TI  - [Dyspnea and dysphagia as the primary manifestation of a rare congenital vascular
      anomaly in an elderly lady: left pulmonary artery sling].

PMID- 19768667
TI  - [Relevance of pathological examinations and lung dust analyses in the context of
      asbestos-associated lung cancer-No. 4104 of the list of occupational diseases in
      Germany].
AB  - This report discusses the relevance of pathological-anatomical examinations and
      lung dust analyses in the context of asbestos-related lung cancer on the basis of
      three case reports. The cases one and two demonstrate a limited performance of
      conventional computed tomography scanning with a resolution of 3 mm for the
      detection of asbestos-related pleural diseases. In these cases, only the autopsy
      was able to confirm the diagnosis of pleural plaques and, therefore, the German
      criteria for occupational disease No. 4104 of the list of the occupational
      diseases were fulfilled. Case three clearly shows that routine pathological
      examinations, especially without the consideration of an occupational disease,
      could not always successfully obtain the diagnosis of a grade I asbestosis. Only
      intense histological examinations (iron-staining, 400 x magnification) in
      combination with lung dust analysis were able to provide such a diagnosis. As
      shown here, pathological-anatomic examinations including lung dust analysis are
      highly valuable for the estimation of asbestos-related lung diseases. A merely
      partial consideration of all possible evidence forms can be responsible for the
      rejection of a reasonable compensation claim for an occupational disease.
      Therefore pathological-anatomic examinations are indispensable today and in the
      future. A definite rejection of occupational disease No. 4104 without an analysis
      of lung parenchyma is not justified.

PMID- 19768668
TI  - Title page: patient with primary myelofibrosis--extramedullary hematopoiesis in
      the pelvicalyceal system and ureters.

PMID- 19768669
TI  - Substrate stiffness affects early differentiation events in embryonic stem cells.
AB  - Embryonic stem cells (ESC) are both a potential source of cells for tissue
      replacement therapies and an accessible tool to model early embryonic
      development. Chemical factors such as soluble growth factors and insoluble
      components of the extracellular matrix are known to affect the differentiation of
      murine ESCs. However, there is also evidence to suggest that undifferentiated
      cells can both sense the mechanical properties of their environment and
      differentiate accordingly. By growing ESCs on flexible polydimethylsiloxane
      substrates with varying stiffness, we tested the hypothesis that substrate
      stiffness can influence ESC differentiation. While cell attachment was unaffected
      by the stiffness of the growth substrate, cell spreading and cell growth were all
      increased as a function of substrate stiffness. Similarly, several genes
      expressed in the primitive streak during gastrulation and implicated in early
      mesendoderm differentiation, such as Brachyury, Mixl1 and Eomes, were upregulated
      in cell cultures on stiffer compared to softer substrates. Finally, we
      demonstrated that osteogenic differentiation of ESCs was enhanced on stiff
      substrates compared to soft substrates, illustrating that the mechanical
      environment can play a role in both early and terminal ESC differentiation. Our
      results suggest a fundamental role for mechanosensing in mammalian development
      and illustrate that the mechanical environment should be taken into consideration
      when engineering implantable scaffolds or when producing therapeutically relevant
      cell populations in vitro.

PMID- 19768670
TI  - Assessment of the potential genotoxic risk of medicinal Tamarindus indica fruit
      pulp extract using in vivo assays.
AB  - Tamarindus indica has been used in folk medicine as an antidiabetic, a digestive
      aid, and a carminative, among other uses. Currently, there is no information in
      the toxicology literature concerning the safety of T. indica extract. We
      evaluated the clastogenic and/or genotoxic potential of fruit pulp extract of
      this plant in vivo in peripheral blood and liver cells of Wistar rats, using the
      comet assay, and in bone marrow cells of Swiss mice, using the micronucleus test.
      The extract was administered by gavage at doses of 1000, 1500 and 2000 mg/kg body
      weight. Peripheral blood and liver cells from Wistar rats were collected 24 h
      after treatment, for the comet assay. The micronucleus test was carried out in
      bone marrow cells from Swiss mice collected 24 h after treatment. The extract
      made with T. indica was devoid of clastogenic and genotoxic activities in the
      cells of the rodents, when administered orally at these three acute doses.

PMID- 19768671
TI  - Glutathione S-transferase M1 and T1 polymorphism in men with idiopathic
      infertility.
AB  - Male infertility is a heterogeneous disorder, with various genetic and
      environmental factors that contribute to the impairment of spermatogenesis.
      Genetic causes are responsible for 60% of cases of idiopathic infertility.
      Polymorphisms of genes that encode detoxifying enzymes of phase II drug
      metabolism can modify their expression or function, affecting the
      biotransformation of toxic compounds to which the male reproductive system is
      exposed. GSTM1 and GSTT1 encode enzymes that are essential in the process of
      detoxification of endogenous and exogenous xenobiotics, facilitating their
      excretion. We examined GSTM1 and GSTT1 polymorphism in 233 men with idiopathic
      infertility seen at the Human Reproduction Service of the Federal University of
      Goias from 2004-2006. Genotype GSTM1/T1 (null) was found in 30/105 normal
      individuals and in 64/128 abnormal individuals, indicating a significant
      association with idiopathic male infertility. The sperm alteration associated
      with greater GSTM1/T1 (null) frequency was decreased sperm count
      (oligozoospermy), which was more frequent in patients with GSTM1 (78.9%) as well
      as in those who had GSTT1 (73.7%), although the difference was not significant.
      Individuals polymorphic for genes GSTM1 and GSTT1 are susceptible to reduction in
      sperm quality and infertility, possibly because oligozoo spermic individuals have
      been affected by GST polymorphism.

PMID- 19768672
TI  - Karyoevolution of the toadfish Thalassophryne nattereri (Batrachoidiformes:
      Batrachoididae).
AB  - The Batrachoididae includes some venomous brackish and marine fish found in the
      Atlantic, Indian and Pacific oceans. This family is composed of 69 species,
      distributed among 19 genera. Species of the genus Thalassophryne have been
      reported along the coast of Rio Grande do Norte (Brazil); T. nattereri has been
      responsible for a large number of human injuries. Little is known about the
      cytogenetic features of this family. We made a karyotypic characterization of T.
      nattereri collected from the estuary of the Apodi/Mossoro River, using
      conventional Giemsa staining, C-banding and silver nitrate-nucleolar organizer
      region technique. There was a modal diploid value of 2n = 46 chromosomes (8m +
      8sm + 24st + 6a; fundamental number = 86). Single ribosomal sites were detected
      in the terminal region on short arms of a subtelocentric pair (19th).
      Heterochromatin segments were preferentially located over centromeric regions in
      some chromosome pairs. Pericentric inversions and Robertsonian rearrangements
      seem to have played a major role in karyotype evolution within this genus of
      toadfish.

PMID- 19768673
TI  - RAPD-based study of genetic variation and relationships among wild fig genotypes
      in Turkey.
AB  - The fig tree (Ficus carica L.) is of significant socio-economic importance in
      Turkey, with 25% of the world's fig production. Genetic variation and
      relationships among 14 wild-grown figs sampled from Coruh Valley in Turkey were
      characterized by random amplified polymorphic DNA (RAPD). Ninety-eight DNA
      fragments were scored after amplification of DNA samples with 13 random primers;
      70% of the scored bands were polymorphic. Genetic distances between the fig
      genotypes ranged from 0.21 to 0.62. Genotypes 08-ART-02 and 08-ART-06 were found
      to be the most closely related, whereas 08-ART-09 and 08-ART-10 were the most
      distant. The 14 wild-grown genotypes were grouped into six main clusters and one
      outgroup. We conclude that RAPD analysis is efficient for genotyping wild-grown
      fig genotypes.

PMID- 19768674
TI  - Gene silencing during development of in vitro-produced female bovine embryos.
AB  - In early development, female embryos (XX) produce twice the transcripts of X
      linked genes compared with male embryos (XY). During the course of development,
      inactivation of the X chromosome equilibrates gene dosage, making the development
      of female embryos viable. Moreover, the biotechnologies used for producing
      embryos in vitro seem to work better with male embryos, making it easier for them
      to reach the blastocyst stage and allow for complete gestation. We investigated
      the expression of three X-linked genes that are involved in development, XIST,
      G6PD, and HPRT, and of the transcript interferon-tau, in male and female bovine
      blastocysts produced by nuclear transfer (NT) and by in vitro fertilization
      (IVF). Oocytes that had been matured in vitro were enucleated and reconstructed
      with somatic cells from adult animals at 18 h post-maturation. After fusion (two
      pulses of 2.25 kv/cm) and chemical activation (5.0 mM ionomycin for 5 min and 2.0
      mM 6-DMAP for 3 h), the oocyte-somatic cell units were cultivated in CR2 with a
      monolayer of granulosa cells at 38.8 degrees C, in a humidified 5% CO(2)
      atmosphere. IVF embryos were inseminated, after centrifugation in a Percoll
      gradient, with 2 x 10(6) sperm/mL TALP medium supplemented with BSA and PHE and
      cultivated under the same conditions as the cloned embryos. We used real-time PCR
      to analyze the gene expression of individual blastocysts compared to expression
      of the housekeeping gene, GAPDH. The gene XIST was expressed in female embryos
      and not in male embryos produced by IVF, though it was expressed at low levels in
      male embryos produced by NT. Unlike previous reports, we found lower levels of
      the transcript of G6PD in females than in males, suggesting double silencing or
      other mechanisms of control of this gene. Female embryos produced by IVF
      expressed the HPRT gene at a higher level than female embryos produced by NT,
      suggesting that gene silencing proceeds faster in NT-produced female embryos due
      to "inactivation memory" from the nucleus donor. In conclusion, male and female
      embryos express different levels of X-chromosome genes and failures of these
      genes that are essential for development could reduce the viability of females.
      Nuclear transfer can modify this relation, possibly due to epigenetic memory,
      leading to frequent failures in nuclear reprogramming.

PMID- 19768675
TI  - A comparison of uptake of metformin and phenformin mediated by hOCT1 in human
      hepatocytes.
AB  - Metformin, a biguanide that has been used to treat type 2 diabetes mellitus, is
      reportedly transported into human hepatocytes by human organic cation transporter
      1 (hOCT1). The objective of this study was to investigate differences in the
      hepatic uptake of metformin and phenformin, a biguanide derivative similar to
      metformin. Special focus was on the role of active transport into cells.
      Experiments were therefore performed using human cryopreserved hepatocytes and
      hOCT1 expressing oocytes. Both biguanides proved to be good substrates for hOCT1.
      However, phenformin exhibited a much higher affinity and transport activity, with
      a marked difference in uptake kinetics compared with metformin. Both biguanides
      were transported actively by hOCT1, with the active transport components much
      greater than passive transport components in both cases, suggesting that
      functional changes in hOCT1 might affect the transport of both compounds to the
      same degree. This study for the first time produced detailed comparative findings
      for uptake profiles of metformin and phenformin in human hepatocytes and hOCT1
      expressing oocytes. It is considered that hOCT1 may not be the only key factor
      that determines the frequency of metformin and phenformin toxicity, considering
      the major contribution of this transporter to the total hepatic uptake and
      comparable width of their therapeutic concentrations.

PMID- 19768676
TI  - The dimeric structure of Sulfolobus solfataricus thioredoxin A2 and the basis of
      its thermostability.

PMID- 19768677
TI  - Improving physical realism, stereochemistry, and side-chain accuracy in homology
      modeling: Four approaches that performed well in CASP8.
AB  - A correct alignment is an essential requirement in homology modeling. Yet in
      order to bridge the structural gap between template and target, which may not
      only involve loop rearrangements, but also shifts of secondary structure elements
      and repacking of core residues, high-resolution refinement methods with full
      atomic details are needed. Here, we describe four approaches that address this
      "last mile of the protein folding problem" and have performed well during CASP8,
      yielding physically realistic models: YASARA, which runs molecular dynamics
      simulations of models in explicit solvent, using a new partly knowledge-based all
      atom force field derived from Amber, whose parameters have been optimized to
      minimize the damage done to protein crystal structures. The LEE-SERVER, which
      makes extensive use of conformational space annealing to create alignments, to
      help Modeller build physically realistic models while satisfying input restraints
      from templates and CHARMM stereochemistry, and to remodel the side-chains.
      ROSETTA, whose high resolution refinement protocol combines a physically
      realistic all atom force field with Monte Carlo minimization to allow the large
      conformational space to be sampled quickly. And finally UNDERTAKER, which creates
      a pool of candidate models from various templates and then optimizes them with an
      adaptive genetic algorithm, using a primarily empirical cost function that does
      not include bond angle, bond length, or other physics-like terms.

PMID- 19768678
TI  - Protein-binding site prediction based on three-dimensional protein modeling.
AB  - Structural information of a protein can guide one to understand the function of
      the protein, and ligand binding is one of the major biochemical functions of
      proteins. We have applied a two-stage template-based ligand binding site
      prediction method to CASP8 targets and achieved high quality results with
      accuracy/coverage = 70/80 (LEE). First, templates are used for protein structure
      modeling and then for binding site prediction by structural clustering of ligand
      containing templates to the predicted protein model. Remarkably, the results are
      only a few percent worse than those one can obtain from native structures, which
      were available only after the prediction. Prediction was performed without
      knowing identity of ligands, and consequently, in many cases the ligand molecules
      used for prediction were different from the actual ligands, and yet we find that
      the prediction was quite successful. The current approach can be easily combined
      with experiments to investigate protein activities in a systematic way.

PMID- 19768679
TI  - Allostery and conformational free energy changes in human tryptophanyl-tRNA
      synthetase from essential dynamics and structure networks.
AB  - The interdependence of the concept of allostery and enzymatic catalysis, and they
      being guided by conformational mobility is gaining increased prominence. However,
      to gain a molecular level understanding of allostery and hence of enzymatic
      catalysis, it is of utter importance that the networks of amino acids
      participating in allostery be deciphered. Our lab has been exploring the methods
      of network analysis combined with molecular dynamics simulations to understand
      allostery at molecular level. Earlier we had outlined methods to obtain
      communication paths and then to map the rigid/flexible regions of proteins
      through network parameters like the shortest correlated paths, cliques, and
      communities. In this article, we advance the methodology to estimate the
      conformational populations in terms of cliques/communities formed by interactions
      including the side-chains and then to compute the ligand-induced population
      shift. Finally, we obtain the free-energy landscape of the protein in
      equilibrium, characterizing the free-energy minima accessed by the protein
      complexes. We have chosen human tryptophanyl-tRNA synthetase (hTrpRS), a protein
      responsible for charging tryptophan to its cognate tRNA during protein
      biosynthesis for this investigation. This is a multidomain protein exhibiting
      excellent allosteric communication. Our approach has provided valuable structural
      as well as functional insights into the protein. The methodology adopted here is
      highly generalized to illuminate the linkage between protein structure networks
      and conformational mobility involved in the allosteric mechanism in any protein
      with known structure.

PMID- 19768680
TI  - Comparative binding energy analysis for binding affinity and target selectivity
      prediction.
AB  - A major challenge in drug design is to obtain compounds that bind selectively to
      their target receptors and do not cause side-effects by binding to other similar
      receptors. Here, we investigate strategies for applying COMBINE (COMparative
      BINding Energy) analysis, in conjunction with PIPSA (Protein Interaction Property
      Similarity Analysis) and ligand docking methods, to address this problem. We
      evaluate these approaches by application to diverse sets of inhibitors of three
      structurally related serine proteases of medical relevance: thrombin, trypsin,
      and urokinase-type plasminogen activator (uPA). We generated target-specific
      scoring functions (COMBINE models) for the three targets using training sets of
      ligands with known inhibition constants and structures of their receptor-ligand
      complexes. These COMBINE models were compared with the PIPSA results and
      experimental data on receptor selectivity. These scoring functions highlight the
      ligand-receptor interactions that are particularly important for binding
      specificity for the different targets. To predict target selectivity in virtual
      screening, compounds were docked into the three protein binding sites using the
      program GOLD and the docking solutions were re-ranked with the target-specific
      scoring functions and computed electrostatic binding free energies. Limits in the
      accuracy of some of the docking solutions and difficulties in scoring them
      adversely affected the predictive ability of the target specific scoring
      functions. Nevertheless, the target-specific scoring functions enabled the
      selectivity of ligands to thrombin versus trypsin and uPA to be predicted.

PMID- 19768681
TI  - Regional covariation and its application for predicting protein contact patches.
AB  - Correlated mutation analysis (CMA) is an effective approach for predicting
      functional and structural residue interactions from multiple sequence alignments
      (MSAs) of proteins. As nearby residues may also play a role in a given functional
      interaction, we were interested in seeing whether covarying sites were clustered,
      and whether this could be used to enhance the predictive power of CMA. A large
      scale search for coevolving regions within protein domains revealed that if two
      sites in a MSA covary, then neighboring sites in the alignment also typically
      covary, resulting in clusters of covarying residues. The program
      PatchD(http://www.uhnres.utoronto.ca/labs/tillier/) was developed to measure the
      covariation between disconnected sequence clusters to reveal patch covariation.
      Patches that exhibit strong covariation identify multiple residues that are
      generally nearby in the protein structure, suggesting that the detection of
      covarying patches can be used in conjunction with traditional CMA approaches to
      reveal functional interaction partners.

PMID- 19768682
TI  - Structure of the EMMPRIN N-terminal domain 1: dimerization via beta-strand
      swapping.

PMID- 19768683
TI  - Solution structure and calcium binding of protein SSO6904 from the
      hyperthermophilic archaeon Sulfolobus solfataricus.

PMID- 19768684
TI  - Structural insights into Staphylococcus aureus enoyl-ACP reductase (FabI), in
      complex with NADP and triclosan.

PMID- 19768686
TI  - Propensity vectors of low-ASA residue pairs in the distinction of protein
      interactions.
AB  - We introduce low-ASA residue pairs as classification features for distinguishing
      the different types of protein interactions. A low-ASA residue pair is defined as
      two contact residues each from one chain that have a small solvent accessible
      surface area (ASA). This notion of residue pairs is novel as it first combines
      residue pairs with the O-ring theory, an influential proposition stating that the
      binding hot spots at the interface are often surrounded by a ring of
      energetically less important residues. As binding hot spots lie in the core of
      the stability for protein interactions, we believe that low-ASA residue pairs can
      sharpen the distinction of protein interactions. The main part of our feature
      vector is 210-dimensional, consisting of all possible low-ASA residue pairs; the
      value of every feature is determined by a propensity measure. Our classification
      method is called OringPV, which uses propensity vectors of protein interactions
      for support vector machine. OringPV is tested on three benchmark datasets for a
      variety of classification tasks such as the distinction between crystal packing
      and biological interactions, the distinction between two different types of
      biological interactions, etc. The evaluation frameworks include within-dataset,
      cross-dataset comparison, and leave-one-out cross-validation. The results show
      that low-ASA residue pairs and the propensity vector description of protein
      interactions are truly strong in the distinction. In particular, many cross
      dataset generalization capability tests have achieved excellent recalls and
      overall accuracies, much outperforming existing benchmark methods.

PMID- 19768685
TI  - Plasmodium falciparum acyl carrier protein crystal structures in disulfide-linked
      and reduced states and their prevalence during blood stage growth.
AB  - Acyl Carrier Protein (ACP) has a single reactive sulfhydryl necessary for
      function in covalently binding nascent fatty acids during biosynthesis. In
      Plasmodium falciparum, the causative agent of the most lethal form of malaria,
      fatty acid biosynthesis occurs in the apicoplast organelle during the liver stage
      of the parasite life cycle. During the blood stage, fatty acid biosynthesis is
      inactive and the redox state of the apicoplast has not been determined. We solved
      the crystal structure of ACP from P. falciparum in reduced and disulfide-linked
      forms, and observe the surprising result that the disulfide in the PfACP cross
      linked dimer is sequestered from bulk solvent in a tight molecular interface. We
      assessed solvent accessibility of the disulfide with small molecule reducing
      agents and found that the disulfide is protected from BME but less so for other
      common reducing agents. We examined cultured P. falciparum parasites to determine
      which form of PfACP is prevalent during the blood stages. We readily detected
      monomeric PfACP in parasite lysate, but do not observe the disulfide-linked form,
      even under conditions of oxidative stress. To demonstrate that PfACP contains a
      free sulfhydryl and is not acylated or in the apo state, we treated blood stage
      parasites with the disulfide forming reagent diamide. We found that the effects
      of diamide are reversed with reducing agent. Together, these results suggest that
      the apicoplast is a reducing compartment, as suggested by models of P. falciparum
      metabolism, and that PfACP is maintained in a reduced state during blood stage
      growth.

PMID- 19768687
TI  - I-TASSER: fully automated protein structure prediction in CASP8.
AB  - The I-TASSER algorithm for 3D protein structure prediction was tested in CASP8,
      with the procedure fully automated in both the Server and Human sections. The
      quality of the server models is close to that of human ones but the human
      predictions incorporate more diverse templates from other servers which improve
      the human predictions in some of the distant homology targets. For the first
      time, the sequence-based contact predictions from machine learning techniques are
      found helpful for both template-based modeling (TBM) and template-free modeling
      (FM). In TBM, although the accuracy of the sequence based contact predictions is
      on average lower than that from template-based ones, the novel contacts in the
      sequence-based predictions, which are complementary to the threading templates in
      the weakly or unaligned regions, are important to improve the global and local
      packing in these regions. Moreover, the newly developed atomic structural
      refinement algorithm was tested in CASP8 and found to improve the hydrogen
      bonding networks and the overall TM-score, which is mainly due to its ability of
      removing steric clashes so that the models can be generated from cluster
      centroids. Nevertheless, one of the major issues of the I-TASSER pipeline is the
      model selection where the best models could not be appropriately recognized when
      the correct templates are detected only by the minority of the threading
      algorithms. There are also problems related with domain-splitting and mirror
      image recognition which mainly influences the performance of I-TASSER modeling in
      the FM-based structure predictions.

PMID- 19768689
TI  - Structural features of the Nostoc punctiforme debranching enzyme reveal the basis
      of its mechanism and substrate specificity.
AB  - The debranching enzyme Nostoc punctiforme debranching enzyme (NPDE) from the
      cyanobacterium Nostoc punctiforme (PCC73102) hydrolyzes the alpha-1,6 glycosidic
      linkages of malto-oligosaccharides. Despite its high homology to
      cyclodextrin/pullulan (CD/PUL)-hydrolyzing enzymes from glycosyl hydrolase 13
      family (GH-13), NPDE exhibits a unique catalytic preference for longer malto
      oligosaccharides (>G8), performing hydrolysis without the transgylcosylation or
      CD-hydrolyzing activities of other GH-13 enzymes. To investigate the molecular
      basis for the property of NPDE, we determined the structure of NPDE at 2.37-A
      resolution. NPDE lacks the typical N-terminal domain of other CD/PUL-hydrolyzing
      enzymes and forms an elongated dimer in a head-to-head configuration. The unique
      orientation of residues 25-55 in NPDE yields an extended substrate binding groove
      from the catalytic center to the dimeric interface. The substrate binding groove
      with a lengthy cavity beyond the -1 subsite exhibits a suitable architecture for
      binding longer malto-oligosaccharides (>G8). These structural results may provide
      a molecular basis for the substrate specificity and catalytic function of this
      cyanobacterial enzyme, distinguishing it from the classical neopullulanases and
      CD/PUL-hydrolyzing enzymes.

PMID- 19768690
TI  - Modelling the association between patient characteristics and the change over
      time in a disease measure using observational cohort data.
AB  - In observational cohort studies we may wish to examine the associations between
      fixed patient characteristics and the longitudinal changes from baseline in a
      repeated outcome measure. Many biological and other outcome measures are known to
      be subject to measurement error and biological variation. In an initial analysis
      we may fit a regression model to all outcome measurements, accounting for all the
      identified sources of variability, and see how the characteristics are linked to
      the change for typical patients. However, the characteristics may also be linked
      to different distributions of the underlying outcome value at baseline, which
      itself may be correlated with the change over time. Therefore, if we wish to
      examine the change over time for patients of different characteristics but with
      the same underlying baseline value then the initial approach is confounded by the
      baseline values. Furthermore, if we attempt to remove this confounding by
      including the observed baseline measure as a covariate in a model for later
      measurements, then this may provide an approximate solution but is likely to
      introduce some bias. We propose a method based on first following the initial
      approach but then, applying a correction to the parameter estimates. This allows
      the predicted trajectories to be plotted and valid significance tests of
      association with characteristics. Our approach is compared with other methods and
      illustrated through a simulation study and an analysis of the association between
      HIV-1 subtype and immunological response after starting antiretroviral therapy.

PMID- 19768691
TI  - Nonparametric non-inferiority analyses in the three-arm design with active
      control and placebo.
AB  - The three-arm design with test treatment, reference treatment and placebo offers
      internal assay sensitivity for a proof of non-inferiority. In this design the
      relative effects known from nonparametric theory are robust tools allowing the
      assessment of non-inferiority in a range of situations. An asymptotic
      nonparametric theory is established in the three-arm design based on the
      asymptotic distribution of rank means under alternative. A rank test for non
      inferiority is derived. Fieller's formula is used to calculate a respective
      confidence interval. The approach is expanded to multicentre studies. The
      simulation studies are conducted demonstrating the accuracy of the methods and an
      example is discussed.

PMID- 19768692
TI  - The inherent flexibility of peptides and protein fragments quantitized by CD in
      conjunction with CCA+.
AB  - ECD spectroscopy is traditionally used for rapid, non-atomic level structure
      analysis of natural products such as peptides and proteins. Unlike globular
      proteins, peptides less frequently adopt a single 3D-fold in a time average
      manner. Moreover, they exhibit an ensemble of conformers composed of a multitude
      of substantially different structures. In principle, both ECD- and vibrational
      circular dichroism (VCD)-spectroscopy are sensitive enough to pick up structural
      information on these dynamic ensembles. However, the interpretation of the raw
      spectral data of these highly dynamic molecular systems can be cumbersome. The
      herein presented Convex Constraint Analysis Plus method, or CCA+ for short
      (http://www.chem.elte.hu/departments/protnmr/cca/), provides a unique opportunity
      for spectral ensemble analysis of peptides, glycopeptides, peptidomimetics, and
      other foldamers. The precision and accuracy of the approach is presented here
      through different peptide model systems. An interesting temperature and pH
      dependent folding and unfolding of a miniprotein (e.g. Tc5b variant) is also
      described. Analysis of CD spectra sets strongly affected by solvent and ion type
      is also introduced to account for severe environmental-induced structure
      influencing effect(s). The deconvolution makes always possible the quantitative
      data analysis even when the interpretation of the deconvolution resulted in pure
      CD curves is complex.

PMID- 19768693
TI  - Dynamic change of T315I BCR-ABL kinase domain mutation in Korean chronic myeloid
      leukaemia patients during treatment with Abl tyrosine kinase inhibitors.
AB  - We analysed the dynamic change of imatinib-resistant mutations in BCR-ABL kinase
      domain focusing on T315I mutation during dasatinib or nilotinib therapy. Fifty
      five imatinib-resistant chronic myeloid leukaemia patients (32 patients with
      imatinib-resistant mutations and 23 patients without mutation) in different
      disease phases were treated with dasatinib (median 17.3 months) or nilotinib
      (median 6.8 months). Among the 32 patients with baseline mutation, mutations
      including M244V, G250E, E255K, M351T, H396R, S417Y, E450K and E459K disappeared
      in 8 patients and new mutations were detected in 9 patients, all of which were
      T315I. Among the 23 patients without baseline mutation, 4 patients showed newly
      developed mutations including T315I, T315I + E459K, M244V and F359V. The T315I
      was the most frequently detected mutation in imatinib therapy (16%, 9 of 55) as
      well as in dasatinib or nilotinib therapy (24%, 11 of 44). Patients with imatinib
      resistant baseline mutations had a higher rate of mutation development during
      dasatinib or nilotinib treatment compared to patients without baseline mutations
      (28% vs. 17%).

PMID- 19768694
TI  - Clofarabine in the treatment of poor risk acute myeloid leukaemia.
AB  - Clofarabine is a second generation nucleoside analogue. It inhibits DNA repair
      and activates the mitochondrial apoptotic pathway leading to cell death. In vitro
      clofarabine has demonstrated synergy with daunorubicin and Ara-C and in phase II
      clinical trials has shown promising activity in poor risk Acute myeloid leukaemia
      (AML) patients. In our institution over a 24 month period 22 AML patients (11 M,
      11 F) with poor risk features, deemed unsuitable for standard therapy, were
      treated with clofarabine, alone (eight patients) or in combination (14 patients)
      for up to three cycles of treatment. The median age was 67.5 years (24-76) with
      16 patients > 60 years. At the time of treatment 18 patients had active AML. Four
      patients intolerant of standard induction received clofarabine as consolidation.
      The overall response rate (ORR) for the 18 patients with active AML was 61%, nine
      patients (50%) achieving a complete response (CR). Induction and consolidation
      were well tolerated with no unexpected toxicities. Predictably, all patients
      developed grade 4 neutropenia but the median duration was only 20 days (17-120).
      Induction mortality was acceptable at 17%. In conclusion, clofarabine (alone or
      in combination) is active in poor risk AML with an acceptable safety profile and
      should be considered a potential option in poor risk AML patients.

PMID- 19768695
TI  - Involvement of hypoxia-inducible factor-1 HiF(1alpha) in IgE-mediated primary
      human basophil responses.
AB  - Basophils play a pivotal role in regulating chronic allergic inflammation as well
      as angiogenesis. Here, we show for the first time that IgE-mediated activation of
      primary human basophils results in protein accumulation of the alpha-subunit of
      hypoxia-inducible factor 1alpha (HIF-1alpha), which is differentially regulated
      compared with signals controlling histamine release. HIF-1 facilitates cellular
      adaptation to hypoxic conditions such as inflammation and tumour growth by
      controlling glycolysis, angiogenesis and cell adhesion. ERK and p38 MAPK, but not
      reactive oxygen species (ROS), ASK1 or PI 3-kinase, were critical for IgE
      mediated accumulation of HIF-1alpha, although the latter crucially affected
      degranulation. Abrogating HIF-1alpha expression in basophils using siRNA
      demonstrated that this protein is essential for vascular endothelial growth
      factor (VEGF) mRNA expression and, consequently, release of VEGF protein. In
      addition, HIF-1alpha protein alters IgE-induced ATP depletion in basophils, thus
      also supporting the production of the pro-allergic cytokine IL-4.

PMID- 19768696
TI  - Novel CD8+ Treg suppress EAE by TGF-beta- and IFN-gamma-dependent mechanisms.
AB  - Although CD8+ Treg-mediated suppression has been described, CD8+ Treg remain
      poorly characterized. Here we identify a novel subset of CD8+ Treg that express
      latency-associated peptide (LAP) on their cell surface (CD8+LAP+ cells) and
      exhibit regulatory activity in vitro and in vivo. Only a small fraction of
      CD8+LAP+ cells express Foxp3 or CD25, although the expression levels of Foxp3 for
      these cells are higher than their LAP- counterparts. In addition to TGF-beta,
      CD8+LAP+ cells produce IFN-gamma, and these cells suppress EAE that is dependent
      on both TGF-beta and IFN-gamma. In an adoptive co-transfer model, CD8+LAP+ cells
      suppress myelin oligodendrocyte glycoprotein (MOG)-specific immune responses by
      inducing or expanding Foxp3+ cells and by inhibiting proliferation and IFN-gamma
      production in vivo. Furthermore, in vivo neutralization of IFN-gamma and studies
      with IFN-gamma-deficient mice demonstrate an important role for IFN-gamma
      production in the function of CD8+LAP+ cells. Our findings identify the
      underlying mechanisms that account for the immunoregulatory activity of CD8+ T
      cells and suggest that induction or amplification of CD8+LAP+ cells may be a
      therapeutic strategy to help control autoimmune processes.

PMID- 19768697
TI  - Thymocyte deletion can bias Treg formation toward low-abundance self-peptide.
AB  - Autoreactive CD4+ T cells can undergo deletion and/or become CD25+Foxp3+ Treg as
      they develop intrathymically, but how these alternative developmental fates are
      specified based on interactions with self-peptide(s) is not understood. We show
      here that thymocytes expressing an autoreactive TCR can be subjected to varying
      degrees of deletion that correlate with the amount of self-peptide. Strikingly,
      among thymocytes that evade deletion, similar proportions acquire Foxp3
      expression. These findings provide evidence that Foxp3+ Treg can develop among
      members of a cohort of autoreactive thymocytes that have evaded deletion by a
      self-peptide, and that deletion and Treg formation can act together to bias the
      Treg repertoire toward low-abundance self-peptide(s).

PMID- 19768698
TI  - Assessing the validity of deriving clinical dementia rating (CDR) global scores
      from independently-obtained functional rating scale (FRS) scores in vascular
      dementia with and without Alzheimer's disease.

PMID- 19768699
TI  - Prevalence and correlates of alcoholism in community-dwelling elderly living in
      Sao Paulo, Brazil.
AB  - OBJECTIVES: To assess the prevalence of alcoholism in elderly living in the city
      of Sao Paulo (Brazil) and investigate associated risk factors. METHODS: A total
      of 1,563 individuals aged 60 years or older, of both genders of three districts
      of different socioeconomic classes (high, medium and low) in the city of Sao
      Paulo (Brazil) were interviewed. The CAGE screening test for alcoholism was
      applied and a structured interview was used to assess associated sociodemographic
      and clinical factors. The tests Mini Mental State Examination, Fuld Object Memory
      Evaluation, The Informant Questionnaire on Cognitive Decline in the Elderly and
      Bayer-Activities of Daily Living Scale were used for cognitive and functional
      assessment. RESULTS: Prevalence of alcoholism was 9.1%. Multivariate regression
      analysis showed that alcoholism was associated with male gender, 'mulatto'
      ethnicity, smoking, and cognitive and functional impairment. In addition, the
      younger the individual and the lower the schooling level, the higher the risk for
      alcoholism. CONCLUSIONS: The results obtained in this study show that alcoholism
      is highly frequent in the community-dwelling elderly living in Sao Paulo, and
      that it is associated with socio-demographic and clinical risk factors similar to
      those reported in the literature. This suggests that alcoholism in the elderly of
      a developing country shares the same basic characteristics seen in developed
      countries. These findings suggest that it is essential for health services and
      professional to be prepared to meet this demand that will significantly grow in
      the next years, especially in developing countries, where the rates of population
      aging are higher than those of developed countries.

PMID- 19768700
TI  - Control of the in vivo biodistribution of hybrid nanoparticles with different
      poly(ethylene glycol) coatings.
AB  - Fluorescent nanoparticles containing a gadolinium oxide core are very attractive
      because they are able to combine both imaging (fluorescence imaging, magnetic
      resonance imaging) and therapy (X-ray therapy and neutron-capture therapy)
      techniques. The exploitation of these multifunctional particles for in vivo
      applications requires accurate control of their biodistribution. The
      postfunctionalization of these particles by four different poly(ethylene glycol)
      derivatives, which differ by chain length and end group, exerts a great influence
      on the zeta potential of the nanoparticles and on their biodistribution after
      intravenous injection to HEK-beta3-tumor-bearing mice. This study reveals that
      the behavior of PEGylated nanoparticles, which was monitored by in vivo
      fluorescence imaging, depends on both the chain length and the end group of the
      PEG chain.

PMID- 19768701
TI  - Efficient recovery of electrophoretic profiles of nucleoside metabolites from
      urine samples by multivariate curve resolution.
AB  - Chemometric techniques usually employed in purity assessment and resolution of
      multicomponent peaks have been applied to analytical data from complex biological
      samples obtained with CE-DAD. In the assessment of the purity of the
      electrophoretic peaks, the orthogonal projection approach, the orthogonal
      projection approach with Durbin-Watson criterion, and the simple-to-use
      interactive self-modeling mixture analysis method have been employed.
      Multivariate curve resolution with alternating least squares has been
      successfully implemented to resolve co-migrating peaks of metabolites in CE-DAD
      and to recover qualitative and quantitative information about co-migrating
      components of urine extract. The main challenge consisted of developing high
      quality multivariate curve resolution with alternating least squares models of
      multicomponent peaks acquired during the CE analysis of nucleoside patterns in 18
      urine samples. The recovered ultraviolet visible (UV-Vis) spectra have been
      employed to identify additional nucleosides, such as 1-methylinosine, 2
      methylguanosine, and 1-methylguanosine, whose presence in the metabolic profile
      produced by the applied CE-DAD method has not yet been recognized. Concentration
      profiles of these compounds can be used in metabonomic studies.

PMID- 19768702
TI  - Analyzing and monitoring of phage-bacteria interaction using CE.
AB  - The utilization of CE for monitoring bacteria-phage interaction was investigated
      in this study. Streptococcus thermophilus and Lactobacillus bulgaricus strains
      and their phages were used as model bacteria and phages for the purpose of
      validation in this study. CE with heterogeneous polymer polyethylene oxide was
      utilized for the separation of intact bacteria and investigation of phage
      bacteria interaction. An intact phage detection was carried out with CZE by
      adding SDS in the running buffer. Calibration graphs of bacteria and phages were
      obtained with R(2) values of 0.963 and 0.937, respectively. S. thermophilus
      strain was infected with its virulent phage B3-X18 for investigation of phage
      bacteria interaction. It was observed in capillary electropherogram that the
      culture was lysed depending on the multiplicity of infection value and it showed
      to be completely lysed when the multiplicity of infection value was 10. The
      interaction of S. thermophilus strain with L. bulgaricus phage was also
      investigated by using a CE and a microbiological method and it was observed that
      the L. bulgaricus phage attached itself to the cell wall of S. thermophilus
      strain without damaging the cell.

PMID- 19768703
TI  - Improvement of gel-separated protein identification by DMF-assisted digestion and
      peptide recovery after electroblotting.
AB  - In-gel digestion of gel-separated proteins is a major route to assist in
      proteomics-based biological discovery, which, however, is often embarrassed by
      its inherent limitations such as the low digestion efficiency and the low
      recovery of proteolytic peptides. For overcoming these limitations, many efforts
      have been directed at developing alternative methods to avoid the in-digestion.
      Here, we present a new method for efficient protein digestion and tryptic peptide
      recovery, which involved electroblotting gel-separated proteins onto a PVDF
      membrane, excising the PVDF bands containing protein of interest, and dissolving
      the bands with pure DMF (> or =99.8%). Before tryptic digestion, NH(4)HCO(3)
      buffer was added to moderately adjust the DMF concentration (to 40%) in order for
      trypsin to exert its activity. Experimental results using protein standards
      showed that, due to actions of DMF in dissolving PVDF membrane and the membrane
      bound substances, the proteins were virtually in-solution digested in DMF
      containing buffer. This protocol allowed more efficient digestion and peptide
      recovery, thereby increasing the sequence coverage and the confidence of protein
      identification. The comparative study using rat hippocampal membrane-enriched
      sample showed that the method was superior to the reported on-membrane tryptic
      digestion for further protein identification, including low abundant and/or
      highly hydrophobic membrane proteins.

PMID- 19768704
TI  - Dynamic light-scattering measurement of sieving polymer solutions for protein
      separation on SDS CE.
AB  - We evaluated the mesh size and homogeneity of polymer network by dynamic light
      scattering and discussed the relationship between the physical properties of
      polymer network and the protein separation behavior by capillary polymer
      electrophoresis. We compared three kinds of sieving polymers in solutions with a
      wide range of molecular weights and concentrations: polyacrylamide and
      polyethylene oxide as flexible polymers, and hydroxyethyl cellulose as a
      semiflexible polymer. We found that the mobility of protein was dominated
      primarily by the mesh size xi, irrespective of the type of sieving polymers, and
      the peak spacing between protein peaks increased drastically in the range of
      xi<10 nm, where the mobility also decreased. And the peak widths were dependent
      on the molecular species of sieving polymers and their homogeneity of polymer
      network. We proposed that a polymer network with a homogenous mesh size of less
      than 10 nm is the best sieving medium for separation of the proteins in the
      molecular weight range 14,300-97,200 Da from the view point of the resolution in
      protein separation.

PMID- 19768705
TI  - Proteomic characterization of plasma-derived clotting factor VIII-von Willebrand
      factor concentrates.
AB  - Proteomic methods were used to identify the levels of impurities in three
      commercial plasma-derived clotting factor VIII-von Willebrand factor (FVIII/VWF)
      concentrates. In all three concentrates, significant amounts of other plasma
      proteins were found. In Octanate and Haemoctin, two concentrates developed in the
      1990s, the major impurities identified were inter-alpha inhibitor proteins,
      fibrinogen and fibronectin. These two concentrates were also found to contain
      additional components such as clotting factor II (prothrombin) that are known
      activators of FVIII. In Wilate, a recently developed FVIII/VWF concentrate, the
      amount of these impurities was significantly reduced. Batch-to-batch variations
      and differences between three investigated products were detected using iTRAQ, an
      isotope labeling technique for comparative MS, demonstrating the potential value
      of this technique for quality control analysis. The importance of thorough
      proteomic investigations of therapeutic FVIII/VWF preparations from human plasma
      is also discussed.

PMID- 19768706
TI  - Quantified characterization of human cutaneous normal scar using multiphoton
      microscopy.
AB  - The morphological alterations of human cutaneous normal scar were quantitatively
      analyzed using multiphoton microscopy (MPM) based on two-photon excited
      fluorescence and second harmonic generation. High-contrast, high-resolution
      images of normal scar and uninjured skin were obtained for comparison. In
      addition, some quantitative parameters have been extracted to quantitatively
      discriminate between normal scar and uninjured skin. The MPM combined with
      quantitative method enable a better understanding of microstructual alterations
      of the epidermis, elastic fiber, and collagen in normal scar. It may lead the way
      to making know the mechanism of normal scar formation and identifying feasible
      therapeutic options.

PMID- 19768707
TI  - Modulation of ascorbic acid metabolism by cytochrome P450 induction revealed by
      metabonomics and transcriptional profiling.
AB  - In the present study, NMR-based urinary metabonomic profiles resulting from
      dosing with widely recognized microsomal enzyme inducers were evaluated in male
      rats. Wistar or Sprague-Dawley rats were dosed daily by oral gavage with
      phenobarbital (PB; 100 mg/kg), diallyl sulfide (DAS; 500 mg/kg), the
      investigational compound DMP-904 (150 mg/kg), or beta-naphthoflavone (BNF; 100
      mg/kg) for 4 days, and urine was collected daily for analysis. Compounds known to
      increase cytochrome P450 2B enzymes, including PB, DAS and DMP-904, increased the
      urinary excretion of gulonic and ascorbic acid in a time-dependent manner,
      reaching a maximum following 3-4 days of dosing. In contrast, BNF, an agent that
      induces primarily Cyp1A enzymes, did not increase gulonic or ascorbic acid
      excretion, despite inducing Cyp1A1 more than 200-fold. Given the metabonomic
      results, hepatic transcriptional changes in the regulation of ascorbic acid
      biosynthesis were determined by RT-PCR. All Cyp2B inducers increased hepatic mRNA
      levels of aldo-keto reductase 1A1, an enzyme that catalyzes the formation of
      gulonic acid from glucuronate with concurrent decreased expression of both
      regucalcin (Rgn), the enzyme responsible for conversion of gulonic acid to gulono
      1, 4-lactone and gulonolactone oxidase (Gulo), the rate-limiting enzyme in
      ascorbate biosynthesis. These effects would be expected to increase levels of
      gulonic acid. In addition, Cyp2B inducers also increased hepatic expression of
      enzymes regulating ascorbic acid reutilization including glutaredoxin reductase
      (Glrx2) and thioredoxin reductase (Txnrd1). In contrast, BNF did not effect
      hepatic expression of any enzyme regulating gulonic or ascorbic acid
      biosynthesis. Thus, some microsomal enzyme inducers alter transcriptional
      regulation of ascorbic acid biosynthesis, and these changes are detected by
      noninvasive metabonomic profiling. However, not all microsomal enzyme inducers
      appear to alter ascorbic acid metabolism. Finally, the work illustrates how
      metabonomic results can direct additional studies to determine the biochemical
      mechanisms underlying changes in urinary metabolite excretion.

PMID- 19768708
TI  - A self-assembled foldamer capsule: combining single and double helical segments
      in one aromatic amide sequence.
AB  - In this manuscript, we present supramolecular capsules based on a new design
      relying on both self-assembly and folding of oligomeric strands. We have designed
      an aromatic amide foldamer in which each monomer encodes three levels of
      information: a specific cavity size, recognition groups for guest binding, and a
      propensity to adopt a single or a double helical motif. Thus, a tetradecameric
      sequence based on four different monomers was encoded so that a wide double
      helical segment resulting from the hybridization of two strands creates a cavity
      in which guests, such as 1,10-decanediol, can be bound. Additionally two narrow
      single helical segments form end-caps and isolate the guest from the solvent. The
      design, synthesis, solid-state and solution-state characterization of duplex
      formation and guest binding are presented.

PMID- 19768709
TI  - Experimental and theoretical studies on some energetic functionalized
      trimethylamine derivatives.
AB  - The synthesis and structural properties (from X-ray diffraction or B3LYP/6-31G(d)
      calculations) of three energetic compounds derived from tris(chloromethyl)amine
      and of tris(chloromethyl)amine itself were investigated and compared to those of
      compounds with similar structures. The compounds have almost planar NC(3) units
      at their amine center, and the substituents bound to the CH(2) groups tend to be
      reactive towards further substitution. Multiple hyperconjugation was used to
      explain these observations.

PMID- 19768710
TI  - Unprecedented FeCl(3)6 H(2)O-promoted skeleton rearrangement of 1-aryl-2,3,4,5
      tetrahydro-1H-3-benzazepines: a new strategy for the synthesis of C1 quaternary
      tetrahydroisoquinolines.

PMID- 19768711
TI  - General access to aminobenzyl-o-carboranes as a new class of carborane
      derivatives: entry to enantiopure carborane-amine combinations.
AB  - The convenient synthesis of original aminobenzyl-o-carboranes, which represent a
      new class of nitrogenated carborane derivatives, is described. These novel
      compounds have been efficiently prepared starting from commercially available
      aromatic aldehydes and monosubstituted o-carboranes via carboranyl alcohols and
      chlorides as intermediates. The key step of this methodology is a selective
      nucleophilic amination under mild conditions that allows the formation of the
      expected amines while limiting the partial deboronation of the carborane cluster.
      This general strategy has been applied to the preparation of a wide variety of
      aminobenzyl-o-carboranes. The extension of this pathway to the synthesis of
      enantiopure carborane-amine combinations is also described.

PMID- 19768712
TI  - Minor enantiomer recycling: metal catalyst, organocatalyst and biocatalyst
      working in concert.
AB  - A minor enantiomer recycling one-pot procedure employing two reinforcing chiral
      catalysts has been developed. Continuous regeneration of the achiral starting
      material is effected via selective enzyme-catalyzed hydrolysis of the minor
      product enantiomer from Lewis acid-Lewis base catalyzed addition of acyl cyanides
      to prochiral aldehydes in a two-phase solvent system. The process provides O
      acylated cyanohydrins in close to perfect enantioselectivities, higher than those
      obtained in the direct process, and in high yields. A combination of a (S,S)
      salen Ti Lewis acid and Candida antarctica lipase B provides the products with R
      absolute configuration, whereas the opposite enantiomer is obtained from the
      (R,R)-salen Ti complex and Candida rugosa lipase.

PMID- 19768713
TI  - Discovery of new natural products by intact-cell mass spectrometry and LC-SPE
      NMR: malbranpyrroles, novel polyketides from thermophilic fungus Malbranchea
      sulfurea.
AB  - Six photosensitive polyketides, malbranpyrroles A-F, were discovered from the
      thermophilic fungus Malbranchea sulfurea by using intact-cell
      desorption/ionization on silicon mass (ICD-MS) and LC-SPE-NMR. These two
      strategies facilitate the searching and structural determination of unstable
      natural products. The ICD-MS indicated that only brown hyphae of M. sulfurea can
      produce malbranpyrroles. The biosynthetic pathway of malbranpyrroles was
      evidenced by 13C isotope precursors and amino acid feeding experiments. The
      cytotoxicity data revealed that the conformation of the conjugated system in
      malbranpyrroles does not affect cytotoxic potency against cancer cell lines. In
      addition, the chlorine atom was shown to be the pharmacophore for cytotoxicity.

PMID- 19768714
TI  - A simple protocol to stabilize gold nanoparticles using amphiphilic block
      copolymers: stability studies and viable cellular uptake.
AB  - Di- and triblock non-ionic copolymers based on poly(ethylene oxide) and
      poly(propylene oxide) were studied for the stabilization of nanoparticles in
      water at high ionic strength. The effect of the molecular architecture (di- vs.
      triblock) of these amphiphilic copolymers was investigated by using gold
      nanoparticles (AuNPs) as probes for colloidal stability. The results demonstrate
      that both di- and triblock copolymers can provide long term stability, and that
      in both cases AuNPs are individually embedded within globules of polymers.
      However, in the case of diblock copolymers, the colloidal stability was related
      to the formation of micelles, in contrast with the case of triblock copolymers,
      which were previously shown to provide good stability even at concentrations at
      which micelles do not form. Quartz crystal microbalance (QCM) experiments showed
      that the presence of the hydrophobic block in the structure of the polymer is
      important to ensure quantitative adsorption upon a gold surface and to limit
      desorption. We demonstrate that with an appropriate choice of polymer, the
      polymer/AuNP hybrids can also undergo filtration and freeze-drying without
      noticeable aggregation, which can be very convenient for further applications.
      Finally, preliminary studies of the cytotoxicity effect on fibroblast cells show
      that the polymer/AuNP hybrids were not cytotoxic. TEM micrographs on ultrathin
      sections of cells after incubation with the colloidal solutions show that the
      nanoparticles were internalized into the cells, conserving their initial size and
      shape.

PMID- 19768715
TI  - Studies on the tandem reaction of 4-Aryl-2,3-allenoates with organozinc reagents:
      a facile route to polysubstituted naphthols.

PMID- 19768716
TI  - Uniform mesoporous silica hexagon and its two-dimensional colloidal crystal.
AB  - Well-ordered mesoporous silica nanoparticles with uniform hexagonal disk shapes
      are synthesized under dilute alkaline conditions with a two-step process,
      separating the nucleation and growth process. The resulting monodisperse hexagons
      can be arranged in a 2-dimensional (2D) ordered periodical super-structure. The
      hexagonal symmetry is similar in both scales. A statistical mechanical cell model
      is applied to analyze consequences of the interesting packing structure,
      including osmotic bulk modulus, phase separation and defects.

PMID- 19768717
TI  - Preferred hydrogen adsorption sites in various MOFs--a comparative computational
      study.
AB  - Force-field based grand-canonical Monte Carlo simulations are employed to predict
      the hydrogen adsorption properties of seven structurally different MOFs. The
      performance of different parameter sets is assessed by comparison with
      experimental data, and the capabilities and limitations of the methodology are
      critically discussed, with a particular emphasis on systems with unsaturated
      metal sites. In addition to adsorption isotherms and isosteric heats of
      adsorption, the preferred adsorption sites are obtained from a detailed analysis
      of the calculated hydrogen density fields. Where possible, these positions are
      compared to the results of neutron diffraction experiments. This study highlights
      the capabilities of computational methods to identify the structural features
      which are most favourable for hydrogen adsorption, providing valuable
      implications for the synthesis of novel MOFs.

PMID- 19768718
TI  - Silica-coated metal nanoparticles.
AB  - The advanced high-quality synthesis of dense and porous silica-coated
      nanostructures is enjoying ever-increasing research interests for their important
      properties and diverse applications, especially for catalytic, controlled
      release, colorimetric diagnostics, photothermal therapy, surface enhanced Raman
      scattering (SERS) detection, and so forth. In this timely Focus Review, we
      summarize the up-to-date synthesis strategies, improved properties, and emerging
      applications of silica-coated metal nanoparticles. In particular, the large scale
      synthesis of silica-coated metal nanoparticles and the recent development of
      hollowed-out silica-coated metal nanoparticles by silica dissolution are
      emphasized for new and practical applications.

PMID- 19768719
TI  - Effect of film thickness on the columnar packing structures of discotic
      supramolecules in thin films.
AB  - The effects of film thickness on the columnar packing structure of discotic
      supramolecules in a thin supported film have been investigated by grazing
      incidence small-angle X-ray scattering technique using magnetically aligned
      cobalt octa(n-decylthio)porphyrazine (CoS10) films on octadecyltrichlorosilane
      (OTS)-functionalized substrates as model systems. Magnetically aligned CoS10
      films with a range of film thicknesses (49-845 nm) form uniaxially oriented 'edge
      on' columnar superstructures with their columnar directors perpendicular to the
      applied magnetic field. However, the orientational ordering of the columnar
      packing in the plane perpendicular to the applied magnetic field is strongly
      dependent on the film thickness. While being damped by the elasticity of the side
      chains of CoS10, the strong interfacial interaction at the film-substrate
      interface propagates up to 50-100 nm from the substrate, maintaining the
      orientation of columnar packing in the plane perpendicular to the applied
      magnetic field. When the distance from the film-substrate interface becomes
      larger than about 100 nm, symmetric tilting of columnar layer orientation, which
      saturates at 11.5 degrees , occurs due to longitudinal edge dislocations induced
      by accumulated elastic deformation.

PMID- 19768720
TI  - Homolytic versus heterolytic dissociation of alkalimetal halides: the effect of
      microsolvation.
AB  - Herein we report density functional calculations of homolytic and heterolytic
      dissociation energies of the diatomic alkalimetal halides MX (M=Li, Na, K, Rb,
      and Cs and X=F, Cl, Br, I, and At) and their corresponding microsolvated
      structures MX(H(2)O)(n) (n=1 to 4). Our results show that the homolytic
      dissociation energy of the MX(H(2)O)(n) species increases with the number of
      water molecules involved in the microsolvated salts. On the other hand, the
      heterolytic dissociation energy follows exactly the opposite trend. As a result,
      while for the isolated diatomic alkalimetal halides, homolytic dissociation is
      always favored over heterolytic dissociation, the latter is preferred for CsF and
      CsCl already for n=2, and for n=4 it is the preferential mode of dissociation for
      more than half of the species studied.

PMID- 19768721
TI  - Helical fibrous nanostructures self-assembled from metal-free phthalocyanine with
      peripheral chiral menthol units.
AB  - (D)- and (L)-enantiomers of a novel metal-free 2(3),9(10),16(17),23(24)
      tetrakis(2-isopropyl-5-methylcyclohexoxyl)phthalocyanine (1) with four chiral
      menthol units attached at the peripheral positions of a phthalocyanine ligand
      have been synthesized, and characterized. Neither the (D)-1 nor the (L)-1
      enantiomer display a circular dichroism (CD) signal in the Soret and Q absorption
      region of the phthalocyanine ligand, indicating the lack of effective chiral
      information transfer from the chiral menthol tails to the phthalocyanine
      chromophore at the molecular level. Their self-assembly properties were
      systematically studied by CD spectroscopy, transmission electron microscopy,
      scanning electron microscopy, and atom force microscopy technique. Although four
      constitutional stereoisomers of each enantiomer were synthesized, because the
      four chiral menthol substituents are randomly located at peripheral positions of
      the phthalocyanine ring, cooperation of intermolecular pi-pi interactions between
      the phthalocyanine rings with chiral discrimination of the chiral side chains of
      the (D)-1 and the (L)-1 enantiomer induces the formation of one-dimensional
      helices with left- and right-handed helical molecular arrangement, respectively,
      according to the CD spectroscopic results. This reveals the effective chiral
      information transfer from the chiral menthol tails to the phthalocyanine
      chromophore at the supermolecular level. The formed one-dimensional helices twist
      around each other to maximize the van der Waals interaction, leading to the
      formation of highly ordered fibrous nanostructures with both right- and left
      handed helicity according to the staggering angles between the neighboring
      phthalocyanine molecules, indicating the hierarchical formation of these fibrous
      nanostructures. Careful inspection of these nanofibers indicates the majority of
      nanofibers with right- and left-handed helicity formed from (D)-1 and (L)-1
      enantiomer, respectively, with the ratio of approximately 1.3-1.4:1 among all the
      fibrous nanostructures obtained. Electronic absorption spectroscopic and X-ray
      diffraction results reveal the H-aggregate nature of these nanofibers. The
      present results, showing part of our continuous effort towards preparation of
      self-assembled nanostructures with helical morphology through molecular design
      and synthesis, will be helpful on providing new insight into chiral information
      transfer and expression for synthetic conjugated systems at the supermolecular
      level.

PMID- 19768722
TI  - Combined pharmacophore modeling, docking, and 3D QSAR studies of ABCB1 and ABCC1
      transporter inhibitors.
AB  - Quinazolinones, indolo- and pyrrolopyrimidines with inhibitory effects toward
      ABCB1 (P-gp) and ABCC1 (MRP1) transporters were studied by pharmacophore
      modeling, docking, and 3D QSAR to describe the binding preferences of the
      proteins. The pharmacophore overlays between dual and/or highly selective
      inhibitors point to binding sites of different topology and physiochemical
      properties for MRP1 and P-gp. Docking of selective inhibitors into the P-gp
      binding cavity by the use of a structural model based on the recently resolved P
      gp structure confirms the P-gp pharmacophore features identified, and reveals the
      interactions of some functional groups and atoms in the structures with
      particular protein residues. The 3D QSAR analysis of the dual-effect inhibitors
      allows satisfactory prediction of the selectivity index of the compounds and
      outlines electrostatics as most important for selectivity. The results from the
      combined modeling approach complement each other and could improve our
      understanding of the protein-ligand interactions involved, and could aid in the
      development of highly selective and potent inhibitors of P-gp and MRP1.

PMID- 19768723
TI  - DOSY NMR applied to analysis of flavonoid glycosides from Bidens sulphurea.
AB  - 2D DOSY 1H NMR has proved to be a useful technique in the identification of the
      molecular skeleton of the four major compounds of ethyl acetate extract of aerial
      parts of Bidens sulphurea (Asteraceae). The combination of this technique with
      HPLC, mass spectrometry and other NMR techniques enabled the identification of
      four flavonoid glycosides: quercetin-3-O-beta-D-galactopyranoside, quercetin-3-O
      beta-D-glycopyranoside, quercetin-3-O-alpha-L-arabinofuranoside and quercetin-3-O
      beta-D-rhamnopyranoside.

PMID- 19768724
TI  - Neuropsychiatric symptoms in Parkinson's disease.
AB  - Neuropsychiatric symptoms are common in Parkinson's disease, even at the earliest
      stages, and have important consequences for quality of life and daily
      functioning, are associated with increased carer burden and increased risk for
      nursing home admission. In addition to cognitive impairment, a wide range of
      neuropsychiatric symptoms have been reported. In this article, the epidemiology,
      clinical course, diagnosis, and management of some of the most common
      neuropsychiatric symptoms in PD are discussed: depression, anxiety, apathy,
      fatigue, and psychotic symptoms. Although much is known regarding the prevalence
      and course of these symptoms, the empirical evidence for how to manage these
      symptoms is limited at best. There is thus an urgent need for systematic studies
      for the pharmacological and non-pharmacological management of these symptoms.

PMID- 19768726
TI  - Hybrid cars may interfere with implanted deep brain stimulators.

PMID- 19768725
TI  - Parkinson's disease tremor is diminished with relaxation guided imagery.
AB  - Patients with Parkinson's disease (PD) may have pronounced tremor that
      exacerbates during stress. To determine whether PD tremor improves with
      relaxation guided imagery (RGI) and relaxing music. Twenty patients with PD with
      moderate to severe tremor participated in sessions where relaxation techniques
      were implemented. Tremor was objectively monitored using an accelerometer. RGI
      dramatically decreased tremor in all 20 patients (baseline 270.38 +/- 85.82 vs.
      RGI 35.57 +/- 43.90 movements per minute P < 0.0001). In 15 patients, RGI
      completely abolished tremor for 1-13 min. Average tremor activity remained
      significantly below baseline both 15 min and 30 min after RGI was discontinued (P
      < 0.001). Patients reported improvement lasting 2-14 hours (mean 6.8 +/- 3.8).
      Relaxing music significantly reduced tremor but to a lesser degree than RGI
      (220.04 +/- 106.53 movements per minute P = 0.01). Self-relaxation had no
      significant effect on tremor. RGI can supplement conventional medical treatments
      for tremor in patients with PD on best medical treatment.

PMID- 19768727
TI  - Quality of life score is primarily affected by the mental rather than the
      physical component in patients with restless legs syndrome.

PMID- 19768728
TI  - An open-label conversion study of pramipexole to ropinirole prolonged release in
      Parkinson's disease.
AB  - Ropinirole prolonged release (PR) is a once daily oral dopamine agonist approved
      for the treatment of Parkinson's disease (PD). The goal of this 4 week, open
      label study was to determine the most effective conversion ratio with the fewest
      adverse effects (AEs) when switching from pramipexole to ropinirole PR. Sixty
      patients with PD taking pramipexole were converted overnight to ropinirole PR at
      ratios of 1:3, 1:4, or 1:5 such that 20 consecutive subjects were enrolled in
      each group. Ropinirole PR dose adjustments were allowed to maintain efficacy or
      to reduce AEs. An overnight switch from pramipexole to ropinirole PR was found to
      be well tolerated and AEs were typical for a dopamine agonist. The most common
      AEs were worsening of PD symptoms, dizziness, somnolence, and nausea, the
      majority of which resolved after dose adjustments. Thirteen subjects discontinued
      ropinirole PR before 4 weeks. These subjects were taking a significantly greater
      dose of pramipexole, the majority greater than 4 mg/day, and tended to have
      longer disease durations. A conversion ratio of 1 mg of pramipexole to 4 mg of
      ropinirole PR resulted in the fewest discontinuations of ropinirole PR, the
      fewest dose adjustments and the largest percentage of subjects that preferred
      ropinirole PR.

PMID- 19768729
TI  - A novel method for systematic analysis of rigidity in Parkinson's disease.
AB  - We propose a novel system that analyzes the components of rigidity in Parkinson's
      disease (PD) usually perceived by physicians, in a very simple and systematic way
      for routine clinical practice. Our system is composed of two compact force
      sensors, a gyroscope, and EMG surface electrodes. Muscle tone was assessed in 24
      healthy elderly subjects and 27 PD patients by passive extension and flexion of
      the elbow joint with ramp-and-hold trajectory. Torque and angle data in the
      dynamic phase were used to calculate "elastic coefficients" in extension and
      flexion, and the mean value of torque in each dynamic phase at each joint angle
      (defined as "Bias") was also calculated. The muscle activity index in the static
      phase (EMG Index) was obtained for both biceps brachii (BB) and triceps brachii
      (TB) muscles. "Elastic coefficients," sum of the "difference of Bias" and "EMG
      Index" for BB all correlated well with UPDRS score. Based on our results,
      Parkinsonian rigidity consists of both an "elastic" component and a "difference
      of Bias" component, and neurologists may assess greater rigidity when either one
      or both components are high in value. The EMG index was useful for
      differentiating PD patients with slight rigidity from healthy elderly adults.

PMID- 19768730
TI  - Brain atrophy and white matter hyperintensities in early Parkinson's disease(a).
AB  - The purpose of this research was to examine the extent of global brain atrophy
      and white matter hyperintensities (WMH) in early Parkinson's disease (PD)
      compared to normal controls (NC), to explore the relationship between the MRI
      variables and cognition in PD. In this multicenter study we included 155 PD
      patients (age 65.6 +/- 9.1 years, disease duration 26.7 +/- 19.9 months) and 101
      age-matched NC. On 3D-T1-WI, we calculated normalized brain volumes using SIENAX
      software. WMH volumes were assessed semiautomatically. In PD patients,
      correlation and regression analyses investigated the association between atrophy
      and WMH outcomes and global, attention-executive, visuospatial, and memory
      cognitive functions. Regression analysis was controlled for age, education,
      depression score, motor severity, cerebrovascular risk, and sex. No significant
      MRI variable volume group differences were found. The models did not retain any
      of the imaging variables as significant predictors of cognitive impairment. There
      was no evidence of brain atrophy or higher WMH volume in PD compared to NC, and
      MRI volumetric measurements were not significant predictors of cognitive
      functions in PD patients. We conclude that global structural brain changes are
      not a major feature in patients with incident PD.

PMID- 19768731
TI  - Localization- and mutation-dependent microRNA (miRNA) expression signatures in
      gastrointestinal stromal tumours (GISTs), with a cluster of co-expressed miRNAs
      located at 14q32.31.
AB  - The molecular biology and clinical behaviour of gastrointestinal stromal tumours
      (GISTs) are associated with their anatomical localization (stomach or intestine),
      and also with the mutation status of the receptor tyrosine kinases KIT and
      PDGFRA. Twelve GISTs were evaluated for differential miRNA expression signatures
      by use of microarrays representing 734 human miRNAs. Thirty-two miRNAs were found
      to be differentially expressed according to localization and mutation status.
      Differential expression was further analysed and confirmed for four miRNAs (miR
      132, miR-221, miR-222, and miR-504) by qRT-PCR in 49 additional GISTs.
      Differentially expressed miRNAs were functionally mapped to KIT/PDGFRA signalling
      and G1/S-phase transition of the cell cycle, revealing 22 predicted miRNA/mRNA
      interactions for ten gene targets from KIT/PDGFRA signalling, and 12 interactions
      for 12 gene targets of G1/S-phase transition. Moreover, the expression of 44
      miRNAs clustered in a genetically imprinted region at 14q32.31 was found to be
      strongly correlated in the microarray analysis. This was confirmed for two
      selected miRNAs (miR-134 and miR-370) from the 14q32.31 cluster by qRT-PCR in 49
      additional GISTs, and the expression of these two miRNAs was significantly lower
      in GISTs with 14q loss, and also in GISTs with tumour progress. miRNA profiling
      may prove to be a key determinant of the biology and clinical features of GISTs.

PMID- 19768732
TI  - Muller cell-derived VEGF is a significant contributor to retinal
      neovascularization.
AB  - Vascular endothelial growth factor (VEGF-A) is a major pathogenic factor and a
      therapeutic target for age-related macular degeneration, diabetic retinopathy,
      and retinopathy of prematurity. Despite intensive effort in the field, the
      cellular mechanisms of VEGF action remain virtually uninvestigated. This
      situation makes it difficult to design cellular target-based therapeutics for
      these diseases. In light of the recent finding that VEGF is a potential
      neurotrophic factor, revealing the cellular mechanisms of VEGF action becomes
      necessary to preserve its beneficial effect and inhibit its pathological function
      in long-term anti-VEGF therapeutics for ocular vascular diseases. We therefore
      generated conditional VEGF knockout mice with an inducible Cre/lox system and
      determined the significance of Muller cell-derived VEGF in retinal development
      and maintenance and ischaemia-induced neovascularizartion and vascular leakage.
      Retinal development in the conditional VEGF knockout mice was analysed by
      examining retinal and choroidal vasculatures and retinal morphology and function.
      Ischaemia-induced retinal neovascularization and vascular leakage in the
      conditional VEGF knockout mice were analysed with fluorescein angiography,
      quantification of proliferative neovascular cells, immunohistochemistry, and
      immunoblotting using an oxygen-induced retinopathy model. Our results
      demonstrated that disruption of Muller cell-derived VEGF resulted in no apparent
      defects in retinal and choroidal vasculatures and retinal morphology and
      function, significant inhibition of the ischaemia-induced retinal
      neovascularization and vascular leakage, and attenuation of the ischaemia-induced
      breakdown of the blood-retina barrier. These results suggest that the retinal
      Muller cell-derived VEGF is a major contributor to ischaemia-induced retinal
      vascular leakage and pre-retinal and intra-retinal neovascularization. The
      observation that a significant, but not complete, reduction of VEGF in the retina
      does not cause detectable retinal degeneration suggests that appropriate doses of
      anti-VEGF agents may be important to the safe treatment of retinal vascular
      diseases.

PMID- 19768733
TI  - Comparison of insulin autoantibody: polyethylene glycol and micro-IAA 1-day and 7
      day assays.
AB  - BACKGROUND: Older studies of diabetes development typically utilized a 7-day
      incubation polyethylene glycol competitive insulin autoantibody assay (CIAA). Our
      standard micro-IAA assay (mIAA) utilizes precipitation with proteins A/G and 1
      day incubation (1-day mIAA), but is less sensitive compared to the CIAA assay.
      METHODS: We performed CIAA and mIAA assays in various conditions. We analyzed
      serum samples from 446 type 1 diabetes patients, from another set of 247 type 1
      diabetes patients within 2 weeks of initiation of insulin treatment, from 150
      healthy control donors, from 22 healthy participants in the diabetes autoimmunity
      study in the young (DAISY), and also coded sera from 50 patients with newly
      diagnosed type 1 diabetes and 50 blood donor control samples. RESULTS: In the
      process of our study, we found that the key condition was the incubation time.
      Therefore, we extended the incubation time to 7 days (7-day mIAA assay). No CIAA
      negative control was positive with either 1-day or 7-day mIAA. In a new onset
      type 1 diabetes and at risk cohorts (DAISY study), the 7-day mIAA identified an
      additional 18% as being positive along with 16% of those who were initially 1-day
      mIAA negative and CIAA positive. Most subjects detectable only with the 7-day
      mIAA assay had intermediate levels of CIAA (80-300 nU/mL) (p = 0.01).
      CONCLUSIONS: The 7-day mIAA assay identifies a small but significant additional
      subset of individuals positive on the CIAA assay, while preserving specificity.

PMID- 19768734
TI  - Micromelosides A-D, four new coumarins from the stem bark of Micromelum falcatum.
AB  - Four new coumarins, micromelosides A-D, together with four known coumarins were
      isolated from the stem bark of Micromelum falcatum. The complete assignments of
      the 1H and 13C NMR chemical shifts for these new compounds were achieved by means
      of 1D and 2D NMR techniques, including 1H-1H COSY, HSQC, HMBC and NOE difference.

PMID- 19768735
TI  - Blood pressure levels in pre-diabetic stages are associated with worse cognitive
      functioning in patients with type 2 diabetes.
AB  - BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with mild decrements in
      cognitive functioning, but the relation of these decrements to metabolic and
      vascular risk factors is unclear. The present study compared the vascular risk
      factor profile over the preceding 16 years between T2DM patients with good
      cognitive functioning and those with poor cognitive functioning. METHODS: The
      Hoorn study is a population-based cohort study on glucose metabolism and vascular
      disease initiated in 1989, with follow-up examinations in 1996-1998, 2000-2001
      and 2005-2007. Cognitive functioning was assessed in 2005-2007. Patients who
      developed T2DM between 1989 and 2000-2001 (n = 64) were divided in tertiles
      (lowest tertile = 'poor cognition', highest tertile = 'good cognition') according
      to a sum score for performance across cognitive domains (SUM) and the domain
      score for information-processing speed (IPS). The time course of vascular risk
      factors from 1989 to 2005-2007 was compared between these tertiles with linear
      mixed models adjusted for age, sex and estimated IQ. RESULTS: Present levels
      (2005-2007) of vascular risk factors did not differ between patients with
      relatively poor or good cognition. However, patients with poor cognition had a 14
      18 mmHg higher systolic blood pressure in 1989 than patients with good cognition.
      There were no differences in lipid profile and body weight at any time during the
      study between the groups. For IPS the T2DM patients with poor cognition even had
      a lower baseline HbA(1c) level than patients with good cognition. CONCLUSIONS:
      Cognitive dysfunction in T2DM is related to the cumulative effects of long-term
      exposure to hypertension, even in pre-DM stages.

PMID- 19768736
TI  - Thiamine and benfotiamine prevent apoptosis induced by high glucose-conditioned
      extracellular matrix in human retinal pericytes.
AB  - BACKGROUND: Early and selective loss of pericytes and thickening of the basement
      membrane are hallmarks of diabetic retinopathy. We reported reduced adhesion, but
      no changes in apoptosis, of bovine retinal pericytes cultured on extracellular
      matrix (ECM) produced by endothelial cells in high glucose (HG). Since human and
      bovine pericytes may behave differently in conditions mimicking the diabetic
      milieu, we verified the behaviour of human retinal pericytes cultured on HG
      conditioned ECM. METHODS: Pericytes were cultured in physiological/HG on ECM
      produced by human umbilical vein endothelial cells in physiological/HG, alone or
      in the presence of thiamine and benfotiamine. Adhesion, proliferation, apoptosis,
      p53 and Bcl-2/Bax ratio (mRNA levels and protein concentrations) were measured in
      wild-type and immortalized human pericytes. RESULTS: Both types of pericytes
      adhered less to HG-conditioned ECM and plastic than to physiological glucose
      conditioned ECM. DNA synthesis was impaired in pericytes cultured in HG on the
      three different surfaces but there were no differences in proliferation. DNA
      fragmentation and Bcl-2/Bax ratio were greatly enhanced by HG-conditioned ECM in
      pericytes kept in both physiological and HG. Addition of thiamine and
      benfotiamine to HG during ECM production completely prevented these damaging
      effects. CONCLUSIONS: Apoptosis is strongly increased in pericytes cultured on
      ECM produced by endothelium in HG, probably due to impairment of the Bcl-2/Bax
      ratio. Thiamine and benfotiamine completely revert this effect. This behaviour is
      therefore completely different from that of bovine pericytes, underlining the
      importance of establishing species-specific cell models to study the mechanisms
      of diabetic retinopathy.

PMID- 19768737
TI  - Quantitative and qualitative methods using fluorescence microscopy for the study
      of modified low density lipoproteins uptake.
AB  - Atherosclerosis and heart disease are the main cause of death in United States.
      The development of atherosclerosis includes lipid deposition and foam cell
      formation in the artery wall. Scavenger Receptors A-I and II (SRA-I/II) have an
      important role of in foam cell formation and atherogenesis. Most of the SRA-I/II
      studies had been performed using Iodine-125-radiolabeled modified low-density
      lipoprotein. This report attempts to validate the use of fluorescence microscopy
      techniques as an alternative to obtain qualitative and quantitative information
      of the uptake of fluorescence-labeled acetylated low-density lipoprotein (AcLDL)
      in adherent CHO cells expressing SRA-I/II. After verifying the protein expression
      of SRA-I and II, uptake was quantified using a Laser Scan Cytometer, and images
      of cells containing fluorescent AcLDL were obtained. A significant increase in
      fluorescence was found in the cells transfected with SRA-I/II vs. those with
      empty vector. When SRA-I/II competitive ligands were used, the uptake of AcLDL
      was significantly decreased. In conclusion, the use of fluorescence microscopy
      techniques in obtaining qualitative and quantitative information of the uptake of
      fluorescence-labeled AcLDL by adherent cells, such as CHO cells, is an
      alternative to the traditional use of radiolabeled iodine.

PMID- 19768738
TI  - Myosin heavy chain composition of tiger (Panthera tigris) and cheetah (Acinonyx
      jubatus) hindlimb muscles.
AB  - Felids have a wide range of locomotor activity patterns and maximal running
      speeds, including the very fast cheetah (Acinonyx jubatas), the roaming tiger
      (Panthera tigris), and the relatively sedentary domestic cat (Felis catus). As
      previous studies have suggested a relationship between the amount and type of
      activity and the myosin heavy chain (MHC) isoform composition of a muscle, we
      assessed the MHC isoform composition of selected hindlimb muscles from these
      three felid species with differing activity regimens. Using gel electrophoresis,
      western blotting, histochemistry, and immunohistochemistry with MHC isoform
      specific antibodies, we compared the MHC composition in the tibialis anterior,
      medial gastrocnemius (MG), plantaris (Plt), and soleus muscles of the tiger,
      cheetah, and domestic cat. The soleus muscle was absent in the cheetah. At least
      one slow (type I) and three fast (types IIa, IIx, and IIb) MHC isoforms were
      present in the muscles of each felid. The tiger had a high combined percentage of
      the characteristically slower isoforms (MHCs I and IIa) in the MG (62%) and the
      Plt (86%), whereas these percentages were relatively low in the MG (44%) and Plt
      (55%) of the cheetah. In general, the MHC isoform characteristics of the hindlimb
      muscles matched the daily activity patterns of these felids: the tiger has daily
      demands for covering long distances, whereas the cheetah has requirements for
      speed and power.

PMID- 19768739
TI  - New evidence for tumour embolism as a mode of metastasis.
AB  - The demonstration that a significant proportion of patients with renal carcinomas
      of the clear cell type have tumour cell clumps or aggregates in venous outflow
      from the kidney has interest from two viewpoints. Firstly, the association of
      this occurrence with high VEGF-A production by the cancer seems to suggest a
      novel mode of 'budding' invasion where nests of tumour cells enter the dilated
      and mechanically fragile new vessels supplying the cancerous growth. Secondly,
      with the association of fragment occurrence and metastatic development, the
      entrance of clumps into the circulation indicates that epithelial-mesenchymal
      transition (EMT) is not an obligatory step for the disseminatory behaviour of all
      cancers.

PMID- 19768740
TI  - Cholinergic switch associated with morphological differentiation in
      neuroblastoma.
AB  - The morphology of malignant cells distinguishes between undifferentiated, poorly
      differentiated and differentiating neuroblastomas and constitutes a strong
      prognostic factor. Spontaneous or treatment-induced maturation characterizes a
      subset of neuroblastomas. It constitutes the basis of retinoic acid treatment to
      improve survival in aggressive neuroblastomas. However, the molecular events that
      drive differentiation are poorly understood. In the present study we have
      investigated the relationships between gene expression profiles and
      differentiation criteria in stroma-poor neuroblastomas. This study included three
      undifferentiated (UN), 20 poorly differentiated (PDN) and 11 differentiating (DN)
      neuroblastomas. These groups could be clearly separated using unsupervised
      clustering methods, which further enabled a major classification impact of genes
      involved in neural development, differentiation and function to be identified.
      UNs are characterized by high ASCL1, high PHOX2B, low GATA2, low TH and low DBH
      expressions. Most PDNs harbour a clear adrenergic phenotype, even in the presence
      of missense PHOX2B mutations. Finally, all DN tumours demonstrate cholinergic
      features. Depending upon their association with adrenergic characteristics, this
      enables dual 'cholinergic/adrenergic' and 'fully cholinergic' neuroblastomas to
      be defined. This suggests that the cholinergic switch, a final specification
      process that occurs physiologically in a minority of sympathetic neurons, is a
      critical step of differentiation in some neuroblastic tumours. This switch is
      associated with a down regulation of DBH that is apparently not strictly
      dependent upon PHOX2B. Conversely, GATA2 and TFAP2B may play critical roles in
      maintaining adrenergic features in poorly differentiated tumours.

PMID- 19768741
TI  - Atypical functional lateralization in children with fetal alcohol syndrome.
AB  - In order to explore effects of prenatal alcohol exposure on functional
      lateralization, item tasks measuring preferences of hand, foot, eye, and ear were
      administered to a sample of 23 children diagnosed with fetal alcohol syndrome
      (FAS) compared with typically developing (TD) children. In addition, a dichotic
      listening task was administered to a subsample of 11 children with FAS and a TD
      group of comparable age, sex and handedness. The children with FAS were
      characterized by increased nonright-handedness compared with TD children. No
      differences were evident for preferential use of foot, eye, or ear. Moreover,
      children with FAS displayed more right ear extinctions during dichotic listening
      relative to TD children, indicating a lack of right ear advantage. The results
      add to findings of decreased manual asymmetry and less left-lateralized speech
      perception in children with developmental disorders, and are further discussed in
      relation to the high incidence of callosal abnormalities in alcohol-exposed
      children.

PMID- 19768743
TI  - Neuroanatomy and volumes of brain structures of a live California sea lion
      (Zalophus californianus) from magnetic resonance images.
AB  - The California sea lion (Zalophus californianus) has been a focal point for
      sensory, communication, cognition, and neurological disease studies in marine
      mammals. However, as a scientific community, we lack a noninvasive approach to
      investigate the anatomy and size of brain structures in this species and other
      free-ranging, live marine mammals. In this article, we provide the first
      anatomically labeled, magnetic resonance imaging-based atlas derived from a live
      marine mammal, the California sea lion. The brain of the California seal lion
      contained more secondary gyri and sulci than the brains of terrestrial
      carnivores. The olfactory bulb was present but small. The hippocampus of the
      California sea lion was found mostly in the ventral position with very little
      extension dorsally, quite unlike the canids and the mustelids, in which the
      hippocampus is present in the ventral position but extends dorsally above the
      thalamus. In contrast to the canids and the mustelids, the pineal gland of the
      California sea lion was strikingly large. In addition, we report three
      dimensional reconstructions and volumes of cerebrospinal fluid, cerebral
      ventricles, total white matter (WM), total gray matter (GM), cerebral hemispheres
      (WM and GM), cerebellum and brainstem combined (WM and GM), and hippocampal
      structures all derived from magnetic resonance images. These measurements are the
      first to be determined for any pinniped species. In California sea lions, this
      approach can be used not only to relate cognitive and sensory capabilities to
      brain size but also to investigate the neurological effects of exposure to
      neurotoxins such as domoic acid.

PMID- 19768744
TI  - The mating system of the Sichuan snub-nosed monkey (Rhinopithecus roxellana).
AB  - This article reports the first genetic study of the mating system of the Sichuan
      snub-nosed monkey (Rhinopithecus roxellana), an endemic and endangered species in
      China. The investigation was carried out in a population (WRT) in the Qinling
      Mountains using data from both field observation and paternity analysis through
      microsatellite DNA profiling. During a mating season, a male on an average
      copulated with 5.7 females. Approximately 18% of the females were observed to
      copulate with more than one male over the study period. The majority of
      copulations (94.5%) were initiated by females. Twenty-eight of 430 observed
      matings were extra-unit copulations. Eight polymorphic microsatellite loci were
      used for paternity analysis. The number of alleles at each locus ranged from 3 to
      7 (mean=4.3). Observed heterozygosity ranged between 0.32 and 0.79. None of the
      loci showed significant deviation from Hardy-Weinberg equilibrium. Results from
      paternity exclusion showed that 12 of 21 (57.1%) immature individuals were sired
      by extra-unit males. Although the basic social unit of snub-nosed monkeys is
      consistent with a polygynous mating system, both field observation and genetic
      data suggests that their mating system is polygamous. Infanticide and inbreeding
      avoidance are the most likely explanations for the promiscuity of female snub
      nosed monkeys.

PMID- 19768745
TI  - Increased expression and cellular localization of lipocalin-type prostaglandin D
      synthase in Helicobacter pylori-induced gastritis.
AB  - Immunological responses in the host can result in different disease outcomes of
      Helicobacter pylori-induced gastritis. Prostaglandin E2 derived from
      cyclooxygenase (COX) and prostaglandin E synthase contribute to gastric
      protection. Recently, prostaglandin D2 was shown to be involved in host immunity
      by chemotactic activity through chemoattractant receptor-homologous molecule
      expressed on Th2 cells (CRTH2), but its role in H. pylori-induced gastritis has
      not been clarified. We determined the expression levels of mRNAs for
      haematopoietic PGD synthase (H-PGDS) and lipocalin-type PGDS (L-PGDS), MIP-1
      alpha, IFN-gamma, IL-4, and CDX2 in H. pylori-induced gastritis mucosa by
      quantitative RT-PCR. We found that L-PGDS was constitutively expressed in the
      epithelium of the glandular base. L-PGDS, but not H-PGDS, was induced on
      fibroblasts close to infiltrating cells in the H. pylori-infected gastric mucosa.
      These fibroblasts co-expressed COX-2. The level of L-PGDS mRNA expression
      decreased as gastritis became more severe. In most of the H. pylori-infected
      gastric mucosa, CCR5(+) cells had more actively infiltrated than had CRTH2(+)
      cells. However, the expression level of IFN-gamma was lower in the mucosa of the
      CRTH2(+) cells-dominantly infiltrating group than that of the less CRTH2
      infiltrating group. Exogenously added PGD2 decreased the H. pylori-induced
      expression of IFN-gamma in peripheral blood mononuclear cells in vitro. The data
      suggest that PGD2 derived from the gastric mucosa and fibroblasts plays
      protective roles against inflammatory changes in H. pylori-induced gastritis.

PMID- 19768747
TI  - NMR-based metabonomics analysis of mouse urine and fecal extracts following oral
      treatment with the broad-spectrum antibiotic enrofloxacin (Baytril).
AB  - The human gastrointestinal tract is home to hundreds of species of bacteria and
      the balance between beneficial and pathogenic bacteria plays a critical role in
      human health and disease. The human infant, however, is born with a sterile gut
      and the complex gastrointestinal host/bacterial ecosystem is only established
      after birth by rapid bacterial colonization. Composition of newborn gut flora
      depends on several factors including type of birth (Ceasarian or natural), manner
      of early feeding (breast milk or formula), and exposure to local, physical
      environment. Imbalance in normal, healthy gut flora contributes to several adult
      human diseases including inflammatory bowel (ulcerative colitis and Crohn's
      disease) and Clostridium difficile associated disease, and early childhood
      diseases such as necrotizing enterocolitis. As a first step towards
      characterization of the role of gut bacteria in human health and disease, we
      conducted an 850 MHz (1)H nuclear magnetic resonance spectroscopy study to
      monitor changes in metabolic profiles of urine and fecal extracts of 15 mice
      following gut sterilization by the broad-spectrum antibiotic enrofloxacin (also
      known as Baytril). Ten metabolites changed in urine following enrofloxacin
      treatment including decreased acetate due to loss of microbial catabolism of
      sugars and polysaccharides, decreased trimethylamine-N-oxide due to loss of
      microbial catabolism of choline, and increased creatine and creatinine due to
      loss of microbial enzyme degradation. Eight metabolites changed in fecal extracts
      of mice treated with enrofloxacin including depletion of amino acids produced by
      microbial proteases, reduction in metabolites generated by lactate-utilizing
      bacteria, and increased urea caused by loss of microbial ureases.

PMID- 19768748
TI  - Arsenic methylation capacity and its correlation with skin lesions induced by
      contaminated drinking water consumption in residents of chronic arsenicosis area.
AB  - Chronic exposure to excess level of arsenic through contaminated drinking water
      is associated with many injuries, among which skin lesions are the most
      prominent. In this study, we measured the concentrations of inorganic arsenic
      (iAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) in the blood
      of the residents of arsenicosis area, who demonstrated different skin lesion
      grade from mild, moderate to advanced. We evaluated the individual methylation
      capacity by two indices of the first and secondary methylation ratio (FMR and
      SMR). We found that SMR of moderate and advanced groups were markedly lower than
      that of mild group. Significant negative correlation was found between SMR of all
      the subjects and the grade of skin lesion, with Spearman's correlation
      coefficient of -0.429 (P = 0.016). Moreover, blood MMA proportion of moderate and
      advanced groups was found to be significantly higher than that of the mild group.
      These results suggest that low secondary arsenic methylation capacity and high
      MMA proportion are associated with the severity of arsenic-related skin lesions.
      Our findings evaluated by blood speciation is consistent with that evaluated by
      the generally accepted urinary arsenic speciation in the relationship between
      arsenic methylation capacity and arsenic-related lesions.

PMID- 19768749
TI  - The normal genital tract of the female California sea lion (Zalophus
      californianus): cyclic changes in histomorphology and hormone receptor
      distribution.
AB  - Changes in reproductive tract histomorphology, and estrogen (ERalpha) and
      progesterone receptor (PR) expression throughout the breeding cycle were
      evaluated in free-ranging stranded female California sea lions (Zalophus
      californianus). Hormone receptor expression in the ovaries, uterus, cervix, and
      vagina was evaluated using an immunohistochemical technique with monoclonal
      antibodies. During a large portion of the cycle, ovaries contained both a corpora
      lutea (CL) and follicles in varying stages of development. In the periods of
      pupping and estrus during June and July, and in the spring morphologic features
      of the endometrium suggested estrogen influence. There were areas of squamous
      differentiation in the pseudostratified columnar epithelium of the cervix and
      vagina in some animals during estrus and in the spring. Estrogen receptor
      immunohistochemical scores were highest during pupping and estrus and in the
      spring and lowest during embryonic diapause. Cyclic changes in uterine PR
      expression throughout the cycle were minimal. Both ERalpha and PR were expressed
      in epithelial and stromal cells throughout the cervix and vagina, however,
      receptor expression was typically higher in the stroma. Stromal cell hormone
      receptors may play an important role in epithelial responses to circulating sex
      hormones. The results of this investigation add to the general knowledge of
      California sea lion reproduction and establish baseline information on
      reproductive tract hormone receptors that will aid in determining the factors
      involved in urogenital cancer development in sea lions.

PMID- 19768750
TI  - Normal morphology and hormone receptor expression in the male California sea lion
      (Zalophus californianus) genital tract.
AB  - Histomorphology and estrogen alpha (ER alpha), and progesterone receptor (PR)
      expression were evaluated in free-ranging stranded male California sea lions
      (Zalophus californianus). Hormone receptor expression was evaluated using an
      immunohistochemical technique with monoclonal antibodies. Estrogen and PRs were
      identified in the efferent ductules, prostate gland, corpus cavernosa, corpus
      spongiosium, penile urethra, and in the epithelium and stroma of both the penis
      and prepuce. In some tissues, ER alpha expression was more intense in the stroma,
      emphasizing the importance of the stroma in hormone-mediated growth and
      differentiation of reproductive organs. To our knowledge, this is the first study
      to localize ER alpha and PR to the epithelium of the glans penis. The results of
      this investigation add to the general knowledge of male California sea lion
      reproduction and suggest that estrogens could have a role in the function of the
      male reproductive tract.

PMID- 19768751
TI  - Immunolocalization of G-protein alpha subunits in the olfactory system of the
      cartilaginous fish Scyliorhinus canicula.
AB  - In the olfactory and vomeronasal systems of vertebrates, the morphology of the
      receptor neurons, the receptor gene family they express, the G-protein coupled
      with the receptor (in particular the G-protein alpha subunit), and their
      projection to the olfactory bulb are correlated. Much information about this
      complicated system have been collected in different groups, but nothing is known
      about Chondrichthyes. In this work, the presence and distribution of
      immunoreactivity for different types of G-protein alpha subunit (Galpha(o),
      Galpha(q) and Galpha(s/olf)) were investigated in the olfactory mucosa and
      olfactory bulb of the shark Scyliorhinus canicula. Only Galpha(o)-like
      immunoreactivity was detected in the olfactory mucosa and bulb, both in tissues
      and homogenates. Its distribution was partially similar to that found in other
      vertebrates: it was localized in the microvillous receptor neurons, in numerous
      axon bundles of the fila olfactoria, in the stratum nervosum and in the most of
      glomeruli in the stratum glomerulosum. No immunoreactivity was instead observed
      in the crypt neurons, the second type of olfactory neurons present in
      cartilaginous fish. The projections of crypt neurons to olfactory bulb probably
      correspond to the few ventrally-located glomeruli which were negative to the
      antiserum against Galpha(o). These data suggest, in S. canicula, different
      olfactory neuron types send projections to the olfactory bulb with a segregated
      distribution, as observed in other vertebrates.

PMID- 19768752
TI  - Three-dimensional serial section computer reconstruction of the arrangement of
      the structural components of the parabronchus of the Ostrich, Struthio camelus
      lung.
AB  - The Ostrich, Struthio camelus is the largest extant bird. The arrangement of the
      airway and the vascular components of the parabronchus of its lung were
      investigated by 3D serial section reconstruction. Modestly developed atrial
      muscles, shallow atria, paucity of infundibulae with preponderant origination of
      the air capillaries (ACs) from the atria and lack of interparabronchial septa,
      structural features that epitomize lungs of most highly derived metabolically
      active volant birds were observed. Intertwined very closely, the ACs and the
      blood capillaries (BCs) are not straight, blind-ended tubules that run in
      contact, counter and parallel to each other as has been claimed and/or modeled.
      Crosscurrent (perpendicular = orthogonal) orientation between the centripetal
      (inward) flow of the venous blood (VB) from the periphery of the parabronchus and
      the flow of air in the parabronchial lumen occur. Also, a countercurrent-like
      arrangement between the ACs which convey air centrifugally (outwards = radially)
      and the BCs that transport venous blood centripetally (inwards) was identified.
      The VB is conveyed to the parabronchus by the interparabronchial arteries and
      delivered to the exchange tissue by the intraparabronchial arterioles: it is then
      arterialized at the infinitely many points where the ACs and the BCs contact.
      Functionally, the crosscurrent arrangement grants a multicapillary serial
      arterialization arrangement which extends the time that the respiratory media,
      air and blood, are exposed to each other. The contribution that the
      countercurrent-like arrangement makes to the gas exchange process remains
      obscure.

PMID- 19768753
TI  - The nature of exocytosis in the yolk trophoblastic layer of silver arowana
      (Osteoglossum bicirrhosum) juvenile, the representative of ancient teleost
      fishes.
AB  - We have chosen the silver arowana (Osteoglossum bicirrhosum), a representative of
      the most ancient teleost family Osteoglossidae, to address the question of yolk
      nutrients utilization. Silver arowana have particularly large eggs (1-1.5 cm of
      diameter) and a unique morphology of the yolk. We present evidence that the yolk
      cytoplasmic zone (ycz) in the "yolksac juveniles" is a very complex structure
      involved in sequential processes of yolk hydrolysis, lipoprotein particles
      synthesis, their transport, and exocytosis. Vacuoles filled with yolk granules in
      different stages of digestion move from the vitellolysis zone through the ycz to
      be emptied into the microvillar interspace in the process of exocytosis. The area
      of the ycz with the abundance of the mitochondria must play an important role in
      providing energy for both the transport of vacuoles and the release of their
      contents. Therefore, we postulate that the function of yolk syncytial layer (ysl)
      as the "early embryonic patterning center" transforms in fish larvae or yolksac
      juveniles into a predominantly specialized role as the yolk trophoblastic layer
      (ytl) involved in yolk nutrients utilization. In addition to discovering the
      mechanism of transformation of the ysl function into ytl function, we suggest
      that the machinery involved in nutrient mobilization and exocytosis in yolk of
      arowana yolksac juveniles can be very attractive system for studies of regulatory
      processes in almost all secretory pathways in animal cells.

PMID- 19768755
TI  - Consensus statement: the use of intravenous immunoglobulin in the treatment of
      neuromuscular conditions report of the AANEM ad hoc committee.
AB  - Intravenous immunoglobulin (IVIG) is a therapeutic biologic agent that has been
      prescribed for over two decades to treat various neuromuscular conditions. Most
      of the treatments are given off-label, as little evidence from large randomized
      trials exists to support its use. Recently, IGIV-C has received an indication for
      the treatment of chronic inflammatory demyelinating polyneuropathy (CIDP).
      Because of the lack of evidence, an ad hoc committee of the AANEM was convened to
      draft a consensus statement on the rational use of IVIG for neuromuscular
      disorders. Recommendations were categorized as Class I-IV based on the strength
      of the medical literature. Class I evidence exists to support the prescription of
      IVIG to treat patients with Guillain-Barre syndrome (GBS), CIDP, multifocal motor
      neuropathy, refractory exacerbations of myasthenia gravis, Lambert-Eaton
      syndrome, dermatomyositis, and stiff person syndrome. Treatment of Fisher
      syndrome, polymyositis, and certain presumed autoimmune neuromuscular disorders
      is supported only by Class IV studies, whereas there is no convincing data to
      substantiate the treatment of inclusion body myopathy (IBM), idiopathic
      neuropathies, brachial plexopathy, or diabetic amyotrophy using IVIG. Treatment
      with IVIG must be administered in the context of its known adverse effects. There
      is little evidence to advise the clinician on the proper dosing of IVIG and
      duration of therapy.

PMID- 19768754
TI  - Electrical impedance myography: Background, current state, and future directions.
AB  - Electrical impedance myography (EIM) is a non-invasive technique for the
      evaluation of neuromuscular disease that relies upon the application and
      measurement of high-frequency, low-intensity electrical current. EIM assesses
      disease-induced changes to the normal composition and architecture of muscle,
      including myocyte atrophy and loss, edema, reinnervation, and deposition of
      endomysial connective tissue and fat. With application of single-frequency
      electrical current, EIM can be used to help grade the severity of neuromuscular
      disease. Assessing electrical impedance across a spectrum of applied frequencies
      and with current flow at multiple orientations relative to major muscle fiber
      direction can provide a more complete picture of the condition of muscle. EIM
      holds the promise of serving as an indicator of disease status. It may be useful
      in clinical trials and in monitoring effectiveness of treatment in individual
      patients; ultimately, it may also find diagnostic application. Ongoing efforts
      have been focused on obtaining a deeper understanding of the basic mechanisms of
      impedance change, studying EIM in a variety of clinical contexts, and further
      refining the methods of EIM data acquisition and analysis.

PMID- 19768756
TI  - Relief from episodic weakness with pyridostigmine in paramyotonia congenita: a
      family study.
AB  - Pyridostigmine relieved episodic weakness in a family with paramyotonia congenita
      resulting from the R1448C mutation in the sodium channel gene. The transmission
      was autosomal dominant and the patients had paradoxical myotonia and exercise
      induced weakness. On electrophysiological studies there were myotonic potentials,
      and there was progressive reduction of compound muscle action potential (CMAP)
      amplitudes after short exercise associated with clinical weakness. Pyridostigmine
      in doses of 60 mg three times daily abolished the drop in the postexercise CMAP
      amplitude and reduced the amplitude decrement to slow rate repetitive
      stimulation, but there continued to be a drop in amplitude on exposure to cold.
      The decline of the CMAP amplitude on exposure to cold was controlled by treatment
      with phenytoin. The clinical and electrophysiological features are discussed in
      relation to therapy with pyridostigmine and phenytoin.

PMID- 19768757
TI  - Campylobacter jejuni abscess, encephalomyelitis, and acute
      polyradiculoneuropathy.
AB  - We report an unusual case of spinal epidural Campylobacter jejuni abscess
      associated with acute polyradiculoneuropathy and parainfectious
      encephalomyelitis. Decompressive surgery, antibiotics, intravenous immunoglobulin
      (IVIg) therapy, and intravenous methylprednisolone resulted in rapid clinical
      improvement. C. jejuni infection can cause both an acute polyradiculoneuropathy
      as well as an encephalomyelitis, and a combined occurrence is possible.

PMID- 19768759
TI  - Evolution of the phenotype in a family with an LMNA gene mutation presenting with
      isolated cardiac involvement.
AB  - The aim of this study is to report the evolution of a phenotype in members of a
      single family carrying the heterozygous exon 1 c.178 C/G, p.Arg 60 Gly LMNA gene
      mutation. All mutated family members underwent neurological and cardiological
      assessments for a period ranging from 10 to 20 years. At onset, 4 affected adult
      members presented a phenotype that required pacemaker implantation. Three
      subjects underwent cardiac transplantation leading to long-term survival in 2 of
      them. One of the 3 longest surviving relatives manifested late lipodystrophy, and
      the other 2 had lipodystrophy, insulin-resistant diabetes, and distal peripheral
      neuropathy. The findings demonstrate that the exon 1 c.178 C/G, p.Arg 60 Gly LMNA
      gene mutation is associated with a novel phenotype featuring cardiac involvement
      followed by late lipodystrophy, diabetes, and peripheral axonal neuropathy.

PMID- 19768760
TI  - Probabilistic muscle characterization using QEMG: application to neuropathic
      muscle.
AB  - Clinicians who use electromyographic (EMG) signals to help determine the presence
      or absence of abnormality in a muscle often, with varying degrees of success,
      evaluate sets of motor unit potentials (MUPs) qualitatively and/or quantitatively
      to characterize the muscle in a clinically meaningful way. The resulting muscle
      characterization can be improved using automated analysis. As such, the intent of
      this study was to evaluate the performance of automated, conventional
      Means/Outlier and Probabilistic methods in converting MUP statistics into a
      concise, and clinically relevant, muscle characterization. Probabilistic methods
      combine the set of MUP characterizations, derived using Pattern Discovery (PD),
      of all MUPs detected from a muscle into a characterization measure that indicates
      normality or abnormality. Using MUP data from healthy control subjects and
      patients with known neuropathic disorders, a Probabilistic method that used
      Bayes' rule to combine MUP characterizations into a Bayesian muscle
      characterization (BMC) achieved a categorization accuracy of 79.7% compared to
      76.4% using the Mean method (P > 0.1) for biceps muscles and 94.6% accuracy for
      the BMC method compared to 85.8% using the Mean method (P < 0.01) for first
      dorsal interosseous muscles. The BMC method can facilitate the determination of
      "possible," "probable," or "definite" levels for a given muscle categorization
      (e.g., neuropathic) whereas the conventional Means and Outlier methods support
      only a dichotomous "normal" or "abnormal" decision. This work demonstrates that
      the BMC method can provide information that may be more useful in supporting
      clinical decisions than that provided by the conventional Means or Outlier
      methods.

PMID- 19768761
TI  - Heteronymous Ia-afferent connections in the upper limb following stroke.
AB  - Synergistic arm movement patterns are common following stroke and may arise
      through enhanced spinally mediated reflex connections between muscles. Our goal
      was to investigate the excitability of heteronymous Ia-afferent pathways in
      people with chronic stroke. Responses to tendon taps of the flexor carpi radialis
      (FCR) muscle were recorded in FCR, biceps brachii (BB), and middle deltoid (MD)
      of 13 people with stroke and 13 controls. Heteronymous reflexes were elicited in
      BB and MD in some, but not all, stroke and control subjects. The prevalence and
      size of the heteronymous responses were not significantly different between
      groups. Homonymous reflex responses in FCR were significantly larger in the
      stroke group. We found that the excitability of heteronymous Ia-mediated pathways
      from FCR to BB and MD muscles is not enhanced following stroke, despite
      exaggerated homonymous reflexes, and they are therefore not likely to contribute
      to coactivation of forearm and more proximal upper limb muscles.

PMID- 19768762
TI  - Voluntary activation in the triceps brachii at short and long muscle lengths.
AB  - The aim was of this study was to determine whether voluntary activation
      calculated using the interpolated twitch technique (ITT) would be underestimated
      by muscle length-induced changes in the twitch amplitude evoked at rest after
      maximum voluntary contraction (MVC) in the elbow extensors. In 12 healthy men,
      calculated voluntary activations were compared at short (20 degrees of elbow
      flexion) and long muscle lengths (120 degrees ) using the actual post-MVC
      doublet, and the predicted post-MVC doublet estimated from linear or nonlinear
      extrapolations. Actual post-MVC doublet amplitudes were smaller at 20 degrees
      versus 120 degrees . At 20 degrees , the predicted post-MVC doublet obtained from
      nonlinear extrapolation was larger, and voluntary activation values improved by 5
      33% at the submaximal voluntary contraction intensities (< or =80% of MVC). When
      voluntary drive is compromised, this method of extrapolation is useful to account
      for mechanical limitations that blunt the actual post-MVC doublet, which
      otherwise leads to underestimation of voluntary activation.

PMID- 19768763
TI  - Tracheal transplant with a prefabricated microsurgical flap.
AB  - OBJECTIVE: To test the viability of a tracheal autotransplant, with an original
      technique using a prefabricated flap from a complete tracheal neovascularized
      segment (CTNVS) of the sternohyoid muscle anastomosed by a microsurgical
      technique. STUDY DESIGN: An experimental study using dogs as an animal model.
      METHODS: Ten mongrel dogs weighing 23 to 40 kg were divided into two groups:
      group I (control), five animals submitted to autotransplant of the CTNVS without
      a microsurgical vascular anastomosis; and group II, five dogs submitted to
      autotransplant of the CTNVS with a microsurgical vascular anastomosis. RESULTS:
      All group I dogs developed respiratory insufficiency and died because of necrosis
      and stenosis of the autotransplanted CTNVS, whereas all group II dogs completed a
      minimum period of 90 days of observation without any clinical changes. Macro- and
      microscopic analysis revealed intact tracheal structures. CONCLUSIONS: The
      present clinical and morphological findings demonstrate that the CTNVS
      autotransplant is viable, when a microsurgical vascular anastomosis is used.

PMID- 19768764
TI  - Normalization reduces the spatial dependency of the jaw-stretch reflex activity
      in the human masseter muscle.
AB  - The jaw-stretch reflex is the short-latency response in the jaw-closing muscles
      after a sudden stretch. The hypothesis whether normalization of the jaw-stretch
      reflex amplitude with respect to prestimulus electromyographic (EMG) activity
      will make the amplitude more independent of the location of the electrodes over
      the masseter muscle was tested. A 5 x 6 electrode grid was used to record the jaw
      stretch reflex from 25 sites over the right masseter muscle of 15 healthy men.
      The results showed that there was a significant site dependency of the
      prestimulus EMG activity and the reflex amplitude. High cross-correlation
      coefficients were found between the spatial distribution of mean prestimulus EMG
      activities and reflex amplitude. When the reflex amplitude was normalized with
      respect to the prestimulus EMG activity, no site dependency was found. In
      conclusion, normalization of the jaw-stretch reflex amplitude by the prestimulus
      EMG activity strongly reduces its spatial dependency.

PMID- 19768765
TI  - Ultrasonographic Tinel sign.
AB  - High-resolution ultrasound has become increasingly useful in the evaluation of
      peripheral nerves. As we have gained experience, clinically helpful
      ultrasonographic signs have been detected. One of these is the ultrasonographic
      Tinel sign, in which paresthesias are produced when the transducer compresses a
      nerve lesion. This sign has not been previously described. We present a case in
      which the ultrasonographic Tinel sign helped accurately guide a nerve biopsy in a
      woman with mononeuritis multiplex.

PMID- 19768766
TI  - Hand construction of quadrifilar wire electrodes for electromyography.
AB  - Array electrodes have become increasingly popular for making surface and
      indwelling electromyographic (EMG) recordings. We describe a method for in-house
      construction of indwelling quadrifilar fine-wire electrodes. Quadrifilar
      electrodes facilitate the mapping of vector myoelectric signatures of motoneuron
      firing activities of the motor nucleus, a procedure referred to as EMG
      decomposition. The finished electrode has four detectors, each 50 mum in
      diameter, arranged in a rhombus pattern. Motor unit recruitment and firing
      information are aids to better understanding control deficits and behaviors
      evidenced in the final common pathway of the central nervous system.

PMID- 19768767
TI  - Relationship of Q-sweat to quantitative sudomotor axon reflex test (QSART)
      volumes.
AB  - Q-Sweat, a commercial quantitative sweat measurement system, is modeled on
      quantitative sudomotor axon reflex testing (QSART). This study investigated the
      sweat response using Q-Sweat and Mayo-QSART recordings under identical conditions
      in healthy normal controls. Ninety-four participants were recruited for this
      study. All participants underwent randomized bilateral QSART recordings over the
      four standard recording regions. For both men and women, Wilcoxon signed rank
      tests of paired differences showed significantly lower volumes at each of the
      four sites for Q-Sweat vs. Mayo-QSART. Linear regression analysis was used to
      estimate the relationship between Q-Sweat and Mayo-QSART volume measurements
      separately for men and women. Although there was variability about the regression
      lines, these fitted models can be used to estimate the expected Mayo-QSART volume
      given an observed Q-Sweat volume, although it is preferable to use the Q-Sweat
      normative database directly. We hypothesize that the constant-current generator
      used in conjunction with Q-Sweat provides a less efficient iontophoresis of
      acetylcholine than the Mayo-constructed constant-current stimulator and results
      in lower volumes.

PMID- 19768768
TI  - Impairment of upper trapezius branch of the spinal accessory nerve during bypass
      grafting: a stretch injury?
AB  - Internal jugular vein catheterization has been implicated in spinal accessory
      nerve (SAN) injuries after coronary artery bypass grafting (CABG). Stretch injury
      due to prolonged positioning during CABG has also been proposed as another
      mechanism of injury. Herein we describe a male patient with left shoulder pain
      and abduction difficulty following CABG, who displayed electromyographic
      abnormalities confined to the left upper trapezius muscle. Internal jugular vein
      catheterization had not been performed during surgery. Although unusual, the
      possibility of upper trapezius muscular branch paralysis should be considered in
      patients with shoulder pain or weakness after CABG.

PMID- 19768769
TI  - Plakins in striated muscle.
AB  - Striated muscle cells contain numerous architectural proteins that contribute to
      the function of muscle as generators of mechanical force. Among these proteins
      are crosslinkers belonging to the plakin family, namely plectin, microtubule
      actin crosslinking factor (ACF7/MACF1), bullous pemphigoid antigen 1
      (Bpag1/dystonin), and desmoplakin. These plakin family members, in particular
      plectin and Bpag1/dystonin, exist as several isoforms. The domain organization of
      these plakin variants dictates their subcellular location and the proteins with
      which they interact. Several studies suggest that plakins exert unique functions
      within various compartments of the muscle cell including the sarcolemma, the
      sarcomere, both neuromuscular and myotendinous junctions in skeletal muscle, and
      the intercalated discs in cardiac muscle. Plakins may also regulate the cellular
      placement and function of specific organelles, notably the nucleus, mitochondria,
      Golgi apparatus, and sarcoplasmic reticulum. Here we review and summarize our
      current knowledge of the function of plakins in striated muscle cells.

PMID- 19768770
TI  - Involvement of PI3K/Akt/TOR pathway in stretch-induced hypertrophy of myotubes.
AB  - Skeletal muscle cells are hypertrophied by mechanical stresses, but the
      underlying molecular mechanisms are not fully understood. Two signaling pathways,
      phosphatidylinositol 3-kinase (PI3K)/Akt to target of rapamycin (TOR) and
      extracellular signal-regulated kinase kinase (MEK) to extracellular signal
      regulated kinase (ERK), have been proposed to be involved in muscle hypertrophy.
      In this study we examined the involvement of these pathways in primary cultures
      of chick skeletal myotubes subjected to passive cyclic stretching for 72 hours, a
      time that was sufficient to induce significant hypertrophy in our preparations.
      Hypertrophy was largely suppressed by wortmannin or rapamycin, inhibitors of PI3K
      or mTOR, respectively. Furthermore, phosphorylation of Akt was enhanced by
      stretching and suppressed by wortmannin. The MEK inhibitor, U0126, exerted a
      minimal influence on stretch-induced hypertrophy. We found that cyclic stretching
      of myotubes activates the PI3K/Akt/TOR pathway, resulting in muscle hypertrophy.
      The MEK/ERK pathway may contribute negatively to spontaneous hypertrophy.

PMID- 19768771
TI  - Determinants of cognitive impairment in elderly myasthenia gravis patients.
AB  - The relationship between myasthenia gravis (MG) and cognitive dysfunction has
      been a matter of debate because of the possible association between peripheral
      and central nervous system (CNS) cholinergic dysfunction. The aim of this study
      was to evaluate cognitive function in a series of elderly MG patients in
      comparison to matched controls. In all, 100 consecutive MG patients aged over 60
      years and 31 matched control subjects underwent an extensive neuropsychological
      test battery to explore multiple cognitive domains. There were no differences in
      cognitive performances between patients and controls. Severe MG was associated
      with impaired attention, constructional praxis, and frontal control. Logistic
      regression analysis showed that advanced age, diabetes, and thyroid dysfunction
      were independently associated with cognitive impairment. This study does not
      support the hypothesis of CNS cholinergic involvement in MG. The impairments of
      attention, memory, and control tasks in MG are related to general visual motor
      slowness and to the concomitant presence of other diseases.

PMID- 19768772
TI  - C-fiber function assessed by the laser doppler imager flare technique and
      acetylcholine iontophoresis.
AB  - Vasodilation induced by both acetylcholine iontophoresis (ACh Ionto) and the
      laser Doppler flare technique (LDIFT) can be used to measure small-fiber
      function. The aim of this study was to compare the neurogenic nature of these
      methods. ACh Ionto and the LDIFT were performed on 10 controls, with and without
      local anesthetic cream. The local anesthetic cream blocks the axon reflex; thus,
      by determining the ratio of hyperemic area to stimulus area before and after
      anesthesia, the neurogenic nature of the hyperemia can be determined. The ratio
      of hyperemic area to stimulus area was significantly reduced by local anesthesia
      in the LDIFT [ratio (mean +/- SD): 2.33 +/- 0.67 with local anesthesia; 6.84 +/-
      1.33 without local anesthesia; P < 0.0001], whereas this ratio was unaffected by
      local anesthesia in the ACh Ionto group (2.61 +/- 0.57 with local anesthesia;
      2.67 +/- 1.27 without local anesthesia). This study confirms that the LDIFT
      measures small-fiber function. In contrast, hyperemia elicited by ACh Ionto
      outside the capsule is not blocked by local anesthesia and is thus non
      neurogenic.

PMID- 19768773
TI  - Anti-ganglioside autoantibodies in type 1 diabetes.
AB  - Type 1 diabetes is an autoimmune disease that is accompanied by an immune
      response against pancreatic cells. As gangliosides are expressed in both
      peripheral nerves and pancreatic cells, we examined the possibility of
      correlation between type 1 diabetes, anti-ganglioside autoantibodies, and
      neuropathy. Fifty diabetic patients and 30 controls with other autoimmune
      diseases underwent neurological examination and search for antibodies to
      gangliosides, glutamic acid decarboxylase (GAD(65)), and tyrosine phosphatase
      (IA2). Sixteen (32%) diabetic patients had neuropathy. Twelve diabetic sera were
      found to have anti-ganglioside autoantibodies. Twenty sera were positive for anti
      GAD(65) and nine for anti-IA2 antibody. Sera from three control patients had anti
      ganglioside autoantibodies. No significant correlation was found between
      autoantibodies, neuropathy, and disease duration. Disease duration was shorter in
      patients with antibodies to GAD(65) and IA2 and longer in neuropathic patients.
      The higher prevalence of antibodies in diabetic patients compared to controls may
      reflect the common pattern of antigens shared by peripheral nerve and pancreatic
      islet cells.

PMID- 19768774
TI  - Structure and function of the molecular chaperone Hsp104 from yeast.
AB  - The molecular chaperone Hsp104 plays a central role in the clearance of
      aggregates after heat shock and the propagation of yeast prions. Hsp104's
      disaggregation activity and prion propagation have been linked to its ability to
      resolubilize or remodel protein aggregates. However, Hsp104 has also the capacity
      to catalyze protein aggregation of some substrates at specific conditions. Hence,
      it is a molecular chaperone with two opposing activities with respect to protein
      aggregation. In yeast models of Huntington's disease, Hsp104 is required for the
      aggregation and toxicity of polyglutamine (polyQ), but the expression of Hsp104
      in cellular and animal models of Huntington's and Parkinson's disease protects
      against polyQ and alpha-synuclein toxicity. Therefore, elucidating the molecular
      determinants and mechanisms underlying the ability of Hsp104 to switch between
      these two activities is of critical importance for understanding its function and
      could provide insight into novel strategies aimed at preventing or reversing the
      formation of toxic protein aggregation in systemic and neurodegenerative protein
      misfolding diseases. Here, we present an overview of the current molecular models
      and hypotheses that have been proposed to explain the role of Hsp104 in
      modulating protein aggregation and prion propagation. The experimental approaches
      and the evidences presented so far in relation to these models are examined. Our
      primary objective is to offer a critical review that will inspire the use of
      novel techniques and the design of new experiments to proceed towards a
      qualitative and quantitative understanding of the molecular mechanisms underlying
      the multifunctional properties of Hsp104 in vivo.

PMID- 19768775
TI  - Hsp70 molecular chaperones and Parkinson's disease.
AB  - Because over expression of Hsp70 molecular chaperones suppresses the toxicity of
      aberrantly folded proteins that occur in Alzheimer's disease (AD), Parkinson's
      disease (PD), amyotrophic lateral sclerosis, and various polyQ-diseases
      (Huntington's disease and ataxias), Hsp70 is garnering attention as a possible
      therapeutic agent for these various diseases. Here, I review progress in this
      fascinating field of molecular chaperones and neurodegeneration and describe our
      current understanding of the mechanisms by which Hsp70 protects cells from the PD
      related protein called alpha-synuclein (alpha-syn).

PMID- 19768776
TI  - A novel alginate hollow fiber bioreactor process for cellular therapy
      applications.
AB  - Gel-matrix culture environments provide tissue engineering scaffolds and cues
      that guide cell differentiation. For many cellular therapy applications such as
      for the production of islet-like clusters to treat Type 1 diabetes, the need for
      large-scale production can be anticipated. The throughput of the commonly used
      nozzle-based devices for cell encapsulation is limited by the rate of droplet
      formation to approximately 0.5 L/h. This work describes a novel process for
      larger-scale batch immobilization of mammalian cells in alginate-filled hollow
      fiber bioreactors (AHFBRs). A methodology was developed whereby (1) alginate
      obstruction of the intra-capillary space medium flow was negligible, (2) extra
      capillary alginate gelling was complete and (3) 83 +/- 4% of the cells seeded and
      immobilized were recovered from the bioreactor. Chinese hamster ovary (CHO) cells
      were used as a model aggregate-forming cell line that grew from mostly single
      cells to pancreatic islet-sized spheroids in 8 days of AHFBR culture. CHO cell
      growth and metabolic rates in the AHFBR were comparable to small-scale alginate
      slab controls. Then, the process was applied successfully to the culture of
      primary neonatal pancreatic porcine cells, without significant differences in
      cell viability compared with slab controls. As expected, alginate-immobilized
      culture in the AHFBR increased the insulin content of these cells compared with
      suspension culture. The AHFBR process could be refined by adding matrix
      components or adapted to other reversible gels and cell types, providing a
      practical means for gel-matrix assisted cultures for cellular therapy.

PMID- 19768777
TI  - Self-assembly of a modified amyloid peptide fragment: pH-responsiveness and
      nematic phase formation.
AB  - The self-assembly of peptide YYKLVFFC based on a fragment of the amyloid beta (A
      beta) peptide, A beta 16-20, KLVFF has been studied in aqueous solution. The
      peptide is designed with multiple functional residues to examine the interplay
      between aromatic interactions and charge on the self-assembly, as well as
      specific transformations such as the pH-induced phenol-phenolate transition of
      the tyrosine residue. Circular dichroism (CD) and Fourier-transform infrared
      (FTIR) spectroscopies are used to investigate the conditions for beta-sheet self
      assembly and the role of aromatic interactions in the CD spectrum as a function
      of pH and concentration. The formation of well-defined fibrils at pH 4.7 is
      confirmed by cryo-TEM (transmission electron microscope) and negative stain TEM.
      The morphology changes at higher pH, and aggregates of short twisted fibrils are
      observed at pH 11. Polarized optical microscopy shows birefringence at a low
      concentration (1 wt.-%) of YYKLVFFC in aqueous solution, and small-angle X-ray
      scattering was used to probe nematic phase formation in more detail. A pH-induced
      transition from nematic to isotropic phases is observed on increasing pH that
      appears to be correlated to a reduction in aggregate anisotropy upon increasing
      pH.

PMID- 19768778
TI  - Modulation of SHP-1 phosphatase activity by monovalent and bivalent SH2
      phosphopeptide ligands.
AB  - A sequence derived from the epithelial receptor tyrosine kinase Ros (pY2267)
      represents a high-affinity binding partner for protein tyrosine phosphatase SHP-1
      and was recently used as lead structure to analyze the recognition requirements
      for the enzyme's N-SH2 domain. Here, we focused on a set of peptides comprising C
      terminally extended linear and conformationally constrained side chain-bridged
      cyclic N-SH2 ligands based on the consensus sequence LxpYhxh(h/b)(h/b) (x = any
      amino acid, h = hydrophobic, and b = basic residue). Furthermore, the bivalent
      peptides described were designed to modulate the activity of SHP-1 through
      binding to both, the N-SH2 domain as well as an independent binding site on the
      surface of the catalytic domain (PTP domain). Consistent with previous
      experimental findings, surface plasmon resonance experiments revealed
      dissociation constants of most compounds in the low micromolar range. One
      peptide, EGLNpYc[KVD]MFPAPEEE--NH(2), displayed favorable binding affinity, but
      reduced ability to stimulate SHP-1. Docking experiments revealed that the binding
      of this ligand occurs in binding mode I, recently described to lead to an
      inhibited activation of SHP-1. In summary, results presented in this study
      suggest that inhibitory N-SH2 ligands of SHP-1 may be obtained by designing
      bivalent compounds that associate with the N-SH2 domain and simultaneously occupy
      a specific binding site on the PTP domain.

PMID- 19768779
TI  - Activation of lactoperoxidase by heme-linked protonation and heme-independent
      iodide binding.
AB  - Lactoperoxidase (LPO), a mammalian secretory heme peroxidase, catalyzes the
      oxidation of thiocyanate by hydrogen peroxide to produce hypothiocyanate, an
      antibacterial agent. Although LPO is known to be activated at acidic pH and in
      the presence of iodide, the structural basis of the activation is not well
      understood. We have examined the effects of pH and iodide concentration on the
      catalytic activity and the structure of LPO. Electrochemical and colorimetric
      assays have shown that the catalytic activity is maximized at pH 4.5. The heme
      Soret absorption band exhibits a small red-shift at pH 5.0 upon acidification,
      which is ascribable to a structural transition from a neutral to an acidic form.
      Resonance Raman spectra suggest that the heme porphyrin core is slightly
      contracted and the Fe-His bond is strengthened in the acidic form compared to the
      neutral form. The structural change of LPO upon activation at acidic pH is
      similar to that observed for myeloperoxidase, another mammalian heme peroxidase,
      upon activation at neutral pH. Binding of iodide enhances the catalytic activity
      of LPO without affecting either the optimum pH of activity or the heme structure,
      implying that the iodide binding occurs at a protein site away from the heme
      linked protonation site.

PMID- 19768780
TI  - Heating-induced conformational change of a novel beta-(1-->3)-D-glucan from
      Pleurotus geestanus.
AB  - Recently, we isolated and purified a neutral polysaccharide (PGN) from edible
      fungus Pleurotus geestanus. Its structure was characterized by a range of
      physical-chemical methods, including high performance anion exchange
      chromatography, uronic acid, and protein analyses, size exclusion chromatography
      with ultraviolet, refractive index and light scattering detectors, and nuclear
      magnetic resonance. Our results revealed that PGN is a novel beta-(1-->3)-D
      glucan with glucose attached to every other sugar residues at Position 6 in the
      backbone. It has a degree of branching of 1/2. Such structure is different from
      typical beta-(1-->3)-D-glucans schizophyllan and lentinan in which DB is 1/3 and
      2/5, respectively. Rheological study showed a very interesting melting behavior
      of PGN in water solution: heating PGN in water leads to two transitions, in the
      range of 8-12.5 degrees C and 25-60 degrees C, respectively. The melting behavior
      and conformational changes were characterized by rheometry, micro-differential
      scan calorimetry, atomic force microscopy, static and dynamic light scattering at
      different temperatures. The first heating-induced transition corresponds to the
      disintegration of polymer bundles into small helical clusters, resembling the
      heating-induced dissociation of SPG in water at 7 degrees C; the second one might
      correspond to the dissociation of helical strands to individual chains. The
      ability of PGN to undergo a conformation/viscosity transition in water upon
      heating is very valuable to immobilize cells or enzymes or therapeutic DNA/RNA,
      which makes PGN a potentially useful biomaterial.

PMID- 19768781
TI  - The effect of deuterium oxide on the stability of the collagen model peptides H
      (Pro-Pro-Gly)(10)-OH, H-(Gly-Pro-4(R)Hyp)(9)-OH, and Type I collagen.
AB  - The collagen triple helix has a larger accessible surface area per molecular mass
      than globular proteins, and therefore potentially more water interaction sites.
      The effect of deuterium oxide on the stability of collagen model peptides and
      Type I collagen molecules was analyzed by circular dichroism and differential
      scanning calorimetry. The transition temperatures (T(m)) of the protonated
      peptide (Pro-Pro-Gly)(10) were 25.4 and 28.7 degrees C in H(2)O and D(2)O,
      respectively. The increase of the T(m) of (Pro-Pro-Gly)(10) measured
      calorimetrically at 1.0 degrees C min(-1) in a low pH solution from the
      protonated to the deuterated solvent was 5.1 degrees C. The increases of the T(m)
      for (Gly-Pro-4(R)Hyp)(9) and pepsin-extracted Type I collagen were measured as
      4.2 and 2.2 degrees C, respectively. These results indicated that the increase in
      the T(m) in the presence of D(2)O is comparable to that of globular proteins, and
      much less than reported previously for collagen model peptides [Gough and
      Bhatnagar, J Biomol Struct Dyn 1999, 17, 481-491]. These experimental results
      suggest that the interaction of water molecules with collagen is similar to the
      interaction of water with globular proteins, when the ratio of collagen to water
      is very small and collagen is monomerically dispersed in the solvent.

PMID- 19768783
TI  - NMR studies of an immunomodulatory benzodiazepine binding to its molecular target
      on the mitochondrial F(1)F(0)-ATPase.
AB  - Bz-423 is an inhibitor of the mitochondrial F(1)F(0)-ATPase, with therapeutic
      properties in murine models of immune diseases. Here, we study the binding of a
      water-soluble Bz-423 analog (5-(3-(aminomethyl)phenyl)-7-chloro- 1-methyl-3
      (naphthalen-2-ylmethyl)-1H-benzo][e][1,4]diazepin-2(3H)-one); (1) to its target
      subunit on the enzyme, the oligomycin sensitivity conferring protein (OSCP), by
      NMR spectroscopy using chemical shift perturbation and cross-relaxation
      experiments. Titration experiments with constructs representing residues 1-120 or
      1-145 of the OSCP reveals that (a) 1 binds to a region of the protein, at the
      minimum, comprising residues M51, L56, K65, V66, K75, K77, and N92, and (b)
      binding of 1 induces conformational changes in the OSCP. Control experiments
      employing a variant of 1 in which a key binding element on the small molecule was
      deleted; it had no perturbational effect on the spectra of the OSCP, which
      indicates that the observed changes with 1 represent specific binding
      interactions. Collectively, these data suggest that 1 might inhibit the enzyme
      through an allosteric mechanism where binding results in conformational changes
      that perturb the OSCP-F(1) interface resulting in disrupted communication between
      the peripheral stalk and the F(1)-domain of the enzyme.

PMID- 19768782
TI  - Interplay between protein homeostasis networks in protein aggregation and
      proteotoxicity.
AB  - The misfolding and aggregation of disease proteins is characteristic of numerous
      neurodegenerative diseases. Particular neuronal populations are more vulnerable
      to proteotoxicity while others are more apt to tolerate the misfolding and
      aggregation of disease proteins. Thus, the cellular environment must play a
      significant role in determining whether disease proteins are converted into toxic
      or benign forms. The endomembrane network of eukaryotes divides the cell into
      different subcellular compartments that possess distinct sets of molecular
      chaperones and protein interaction networks. Chaperones act as agonists and
      antagonists of disease protein aggregation to prevent the accumulation of toxic
      intermediates in the aggregation pathway. Interacting partners can also modulate
      the conformation and localization of disease proteins and thereby influence
      proteotoxicity. Thus, interplay between these protein homeostasis network
      components can modulate the self-association of disease proteins and determine
      whether they elicit a toxic or benign outcome.

PMID- 19768785
TI  - BuildBeta--a system for automatically constructing beta sheets.
AB  - We describe a method that can thoroughly sample a protein conformational space
      given the protein primary sequence of amino acids and secondary structure
      predictions. Specifically, we target proteins with beta-sheets because they are
      particularly challenging for ab initio protein structure prediction because of
      the complexity of sampling long-range strand pairings. Using some basic packing
      principles, inverse kinematics (IK), and beta-pairing scores, this method creates
      all possible beta-sheet arrangements including those that have the correct
      packing of beta-strands. It uses the IK algorithms of ProteinShop to move alpha
      helices and beta-strands as rigid bodies by rotating the dihedral angles in the
      coil regions. Our results show that our approach produces structures that are
      within 4-6 A RMSD of the native one regardless of the protein size and beta-sheet
      topology although this number may increase if the protein has long loops or
      complex alpha-helical regions.

PMID- 19768784
TI  - PIE-efficient filters and coarse grained potentials for unbound protein-protein
      docking.
AB  - Identifying correct binding modes in a large set of models is an important step
      in protein-protein docking. We identified protein docking filter based on overlap
      area that significantly reduces the number of candidate structures that require
      detailed examination. We also developed potentials based on residue contacts and
      overlap areas using a comprehensive learning set of 640 two-chain protein
      complexes with mathematical programming. Our potential showed substantially
      better recognition capacity compared to other publicly accessible protein docking
      potentials in discriminating between native and nonnative binding modes on a
      large test set of 84 complexes independent of our training set. We were able to
      rank a near-native model on the top in 43 cases and within top 10 in 51 cases. We
      also report an atomic potential that ranks a near-native model on the top in 46
      cases and within top 10 in 58 cases. Our filter+potential is well suited for
      selecting a small set of models to be refined to atomic resolution.

PMID- 19768786
TI  - Asymmetrically simultaneous synthesis of L-homophenylalanine and N6-protected-2
      oxo-6-amino-hexanoic acid by engineered Escherichia coli aspartate
      aminotransferase.
AB  - L-Homophenylalanine (L-HPA) and N(6)-protected-2-oxo-6-amino-hexanoic acid (N(6)
      protected-OAHA) can be used as building blocks for the manufacture of angiotensin
      converting enzyme inhibitors. To synthesize L-HPA and N(6)-protected-OAHA
      simultaneously from 2-oxo-4-phenylbutanoic acid (OPBA) and N(6)-protected-L
      lysine, several variants of Escherichia coli aspartate aminotransferase (AAT)
      were developed by site-directed mutagenesis and their catalytic activities were
      investigated. Three kinds of N(6)-protected-L-lysine were tested as potential
      amino donors for the bioconversion process. AAT variants of R292E/L18H and
      R292E/L18T exhibited specific activities of 0.70+/-0.01 U/mg protein and 0.67+/
      0.02 U/mg protein to 2-amino-6-tert-butoxycarbonylamino-hexanoic acid (BOC
      lysine) and 2-amino-6-(2,2,2-trifluoro-acetylamino)-hexanoic acid, respectively.
      E. coli cells expressing R292E/L18H variant were able to convert OPBA and BOC
      lysine to L-HPA and 2-oxo-6-tert-butoxycarbonylamino-hexanoic acid (BOC-OAHA)
      with 96.2% yield in 8 h. This is the first report demonstrating a process for the
      simultaneous production of two useful building blocks, L-HPA and BOC-OAHA.

PMID- 19768787
TI  - Nerve regeneration following spinal cord injury using matrix metalloproteinase
      sensitive, hyaluronic acid-based biomimetic hydrogel scaffold containing brain
      derived neurotrophic factor.
AB  - Spinal cord injury leads to the permanent loss of motor and sensory function in
      the body. To enhance spinal cord regeneration, we used a hyaluronic acid-based
      hydrogel as a three-dimensional biomimetic scaffold for peptides and growth
      factors. Three components were used to provide guidance cues: a matrix
      metalloproteinase peptide crosslinker, an IKVAV (Ile- Lys-Val-Ala-Val) peptide
      derived from laminin, and brain-derived neurotrophic factor (BDNF). Human
      mesenchymal stem cells (hMSCs) were cultured in hydrogels in vitro for 10 days to
      induce neuronal differentiation of hMSCs. Based on gene-expression data, the
      matrix metalloproteinase-sensitive peptide, IKVAV peptide, and BDNF were critical
      in the differentiation of hMSCs. Remodeling activity was found to be a key factor
      in guiding neural differentiation of stem cells. To test this approach in vivo,
      we used the spinal cord injured rat model and five different hydrogel
      compositions. Samples were injected into the intrathecal space, and animals were
      monitored for 6 weeks. Compared to all other groups, animals injected with BDNF
      containing hydrogels showed the greatest improvement on locomotive tests (Basso
      Beattie-Bresnahan score) during the initial stage after injury. These results
      suggest that hyaluronic acid-based hydrogels containing IKVAV and BDNF create
      microenvironments that foster differentiation of stem cells along the neural cell
      lineage, and they could be used to facilitate nerve regeneration after spinal
      cord injury.

PMID- 19768788
TI  - In vitro evaluation of the bioactive factors preserved in porcine small
      intestinal submucosa through cellular biological approaches.
AB  - The objective of this study was to develop cellular biological approaches to
      evaluate the potential effect of bioactive factors in porcine small intestinal
      submucosa (SIS) on bladder regeneration and angiogenesis. For this purpose, we
      cultured human bladder smooth muscle cell (HBSMC) and human umbilical vein
      endothelial cell (HUVEC), and then used cellular biological techniques to
      characterize in vitro biological effect of SIS components on HBSMC and HUVEC. Our
      results indicated that the SIS components had stimulated the attachment,
      proliferation, and migration of HBSMC and HUVEC, as well as tube formation by
      HUVEC on Matrigel. These results implied that the SIS might have preserved a
      mixture of bioactive factors including cell adhesion factors, mitogenic factors,
      chemotactic cytokines, and angiogenic factors, and these bioactive factors would
      have the potential of promoting bladder regeneration and angiogenesis. In
      conclusion, these cellular biological approaches might be helpful and effective
      for evaluation of the bioactive factors preserved in porcine SIS before it is
      used for bladder augmentation in humans.

PMID- 19768789
TI  - PEGylation of interleukin-10 for the mitigation of enhanced pain states.
AB  - The anti-inflammatory cytokine interleukin-10 (IL-10) shows promise for the
      treatment of neuropathic pain, but for IL-10 to be clinically useful as a short
      term therapeutic its duration needs to be improved. In this study, IL-10 was
      covalently modified with polyethylene glycol (PEG) with the goal of stabilizing
      and increasing protein levels in the CSF to improve the efficacy of IL-10 for
      treating neuropathic pain. Two different PEGylation methods were explored in
      vitro to identify suitable PEGylated IL-10 products for subsequent in vivo
      testing. PEGylation of IL-10 by acylation yielded a highly PEGylated product with
      a 35-fold in vitro biological activity reduction. PEGylation of IL-10 by
      reductive amination yielded products with a minimal number of PEG molecules
      attached and in vitro biological activity reductions of approximately 3-fold. In
      vivo collections of cerebrospinal fluid after intrathecal administration
      demonstrated that 20 kDa PEG attachment to IL-10 increased the concentration of
      IL-10 in the cerebrospinal fluid over time. Relative to unmodified IL-10, the 20
      kDa PEG-IL-10 product exhibited an increased therapeutic duration and magnitude
      in an animal model of neuropathic pain. This suggests that PEGylation is a viable
      strategy for the short-term treatment or, in conjunction with other approaches,
      the long-term treatment of enhanced pain states.

PMID- 19768790
TI  - Influence of FGF2 and PEG hydrogel matrix properties on hMSC viability and
      spreading.
AB  - In this study, three-dimensional (3-D) poly(ethylene glycol) (PEG) hydrogel
      arrays were used to screen for the effects of fibroblast growth factor-2 (FGF2),
      combined with multiple hydrogel matrix parameters, on human mesenchymal stem cell
      (hMSC) viability and spreading. In particular, we examined the effects of FGF2
      while co-varying hydrogel matrix degradability, cell adhesion ligand type, and
      cell adhesion ligand density. FGF2 significantly improved viability of hMSCs in a
      dose-dependent manner in both nondegrading and degrading PEG hydrogels in the
      absence of extracellular matrix-derived cell adhesion ligands. The presence of a
      small molecule that inhibits autophosphorylation of the FGF2 receptor blocked the
      effects of FGF2 on hMSC viability in PEG hydrogels, both in the presence and
      absence of the Arg-Gly-Asp-Ser-Pro (RGDSP) ligand. FGF2 effects on hMSC viability
      were less pronounced when FGF2 was presented in combination with the RGDSP cell
      adhesion ligand or the IKVAV cell adhesion ligand in nondegrading PEG hydrogels.
      Importantly, spread hMSC morphologies were observed and quantified in a select
      subset of hydrogel networks, which were degradable and included both FGF2 and
      RGDSP. These results indicate that the hydrogel arrays described here can be used
      to efficiently study the influence of soluble and insoluble hydrogel matrix
      parameters on stem cell behavior, and to identify synthetic, 3-D environments
      that promote specific hMSC behaviors.

PMID- 19768791
TI  - Generation of reactive oxygen species from porous silicon microparticles in cell
      culture medium.
AB  - Nanostructured (porous) silicon is a promising biodegradable biomaterial, which
      is being intensively researched as a tissue engineering scaffold and drug
      delivery vehicle. Here, we tested the biocompatibility of non-treated and
      thermally-oxidized porous silicon particles using an indirect cell viability
      assay. Initial direct cell culture on porous silicon determined that human lens
      epithelial cells only poorly adhered to non-treated porous silicon. Using an
      indirect cell culture assay, we found that non-treated microparticles caused
      complete cell death, indicating that these particles generated a toxic product in
      cell culture medium. In contrast, thermally-oxidized microparticles did not
      reduce cell viability significantly. We found evidence for the generation of
      reactive oxygen species (ROS) by means of the fluorescent probe 2',7'
      dichlorofluorescin. Our results suggest that non-treated porous silicon
      microparticles produced ROS, which interacted with the components of the cell
      culture medium, leading to the formation of cytotoxic species. Oxidation of
      porous silicon microparticles not only mitigated, but also abolished the toxic
      effects.

PMID- 19768792
TI  - Imperfect hybrid layers created by an aggressive one-step self-etch adhesive in
      primary dentin are amendable to biomimetic remineralization in vitro.
AB  - Degradation of hybrid layers created in primary dentin occurs as early as 6
      months in vivo. Biomimetic remineralization utilizes "bottom-up" nanotechnology
      principles for interfibrillar and intrafibrillar remineralization of collagen
      matrices. This study examined whether imperfect hybrid layers created in primary
      dentin can be remineralized. Coronal dentin surfaces were prepared from extracted
      primary molars and bonded using Adper Prompt L-Pop and a composite. One
      millimeter-thick specimen slabs of the resin-dentin interface were immersed in a
      Portland cement-based remineralization medium that contained two biomimetic
      analogs to mimic the sequestration and templating functions of dentin
      noncollagenous proteins. Specimens were retrieved after 1-6 months. Confocal
      laser scanning microscopy was used for evaluating the permeability of hybrid
      layers to Rhodamine B. Transmission electron microscopy was used to examine the
      status of remineralization within hybrid layers. Remineralization at different
      locations of the hybrid layers corresponded with quenching of fluorescence within
      similar locations of those hybrid layers. Remineralization was predominantly
      intrafibrillar in nature as interfibrillar spaces were filled with adhesive
      resin. Biomimetic remineralization of imperfect hybrid layers in primary human
      dentin is a potential means for preserving bond integrity. The success of the
      current proof-of-concept, laterally diffusing remineralization protocol warrants
      development of a clinically applicable biomimetic remineralization delivery
      system.

PMID- 19768793
TI  - Artificial cartilage made from a novel double-network hydrogel: In vivo effects
      on the normal cartilage and ex vivo evaluation of the friction property.
AB  - This study evaluated the in vivo influence of a poly-(2-Acrylamido-2
      methylpropane sulfonic acid)/poly-(N,N'-dimetyl acrylamide) (PAMPS/PDMAAm) double
      network (DN) hydrogel on counterface cartilage in rabbit knee joints and its ex
      vivo friction properties on normal cartilage. In the first experiment, the DN gel
      was implanted in a surgically created defect in the femoral trochlea of rabbit
      knee joints and the left knee was used as the control. Evaluations using a
      confocal laser scanning microscopy demonstrated that the DN gel did not affect
      the surface microstructure (surface roughness, the number of small pits) of the
      counterface cartilage in vivo at 4 and 12 weeks. The histology also showed that
      the DN gel hadno pathological damage on the cartilage matrices and cells at 4
      weeks. However, two of the five DN gel-implanted knees showed mild irregularity
      on the counterface cartilage surface at 12 weeks. In the second experiment, the
      friction property between the normal and the artificial cartilage was determined
      using a joint simulator apparatus. The ex vivo mean friction coefficient of the
      DN gel to normal cartilage was 0.029, while that of the normal-to-normal
      cartilage articulation was 0.188. The coefficient of the DN gel-to-normal
      cartilage articulation was significantly lower than that of the normal-to-normal
      cartilage articulation (p < 0.0001). This study suggested that the PAMPS/PDMAAm
      DN gel has very low friction coefficient on normal cartilage and has no
      significant detrimental effects on counterface cartilage in vivo, and can be a
      promising material to develop the artificial cartilage.

PMID- 19768794
TI  - Effects of cell concentration and collagen concentration on contraction kinetics
      and mechanical properties in a bone marrow stromal cell-collagen construct.
AB  - A cell-collagen construct is commonly used to investigate the phenomenon of wound
      healing and to estimate the variables for tissue engineering. The purpose of this
      study was to assess the effects of cell concentration and collagen concentration
      on the contraction kinetics and mechanical properties of bone marrow stromal cell
      (BMSC) seeded collagen lattices. To investigate the effects of both variables on
      the contraction kinetics, the construct contraction was monitored up to 13 days.
      Incremental stress- relaxation tests were carried out after a 2-week incubation
      to obtain the stress-strain profiles, which were subsequently assessed in a
      quasilinear viscoelastic (QLV) model. During contraction, aligned BMSCs were
      observed first in the interior portion of the ring, followed by the middle
      portion and finally in the exterior portion. Constructs seeded with a higher
      initial cell concentration (higher than 1 x 10(5) cells/mL) or lower initial
      collagen concentration (lower than 2 mg/mL) exhibited faster contraction, higher
      ultimate stress, and superior elasticity and reduced relaxation behavior (p <
      0.05). The cell-collagen model was successfully used to yield information
      regarding the initial cell concentration and the initial collagen concentration
      on contraction kinetics and mechanical behavior, which may have possible
      application in tissue engineering.

PMID- 19768795
TI  - The topographical effect of electrospun nanofibrous scaffolds on the in vivo and
      in vitro foreign body reaction.
AB  - Topographical cues play an important role in influencing cellular behavior and
      are considered as significant parameters to be controlled in tissue engineering
      applications. This work investigated the biocompatibility with regard to scaffold
      architecture and topographical effect of nanofibrous scaffolds on the in vivo and
      in vitro foreign body reaction. Random and aligned polycaprolactone (PCL)
      nanofibers were fabricated by electrospinning technique, with diameters of 313 +/
      5 nm and 506 +/- 24 nm, respectively. Primary monocytes isolated from five human
      donors were cultured on PCL nanofibers, PCL film, and RGD-coated glass in vitro
      and cell density and morphology was evaluated at time points of day 0 (2 h), day
      3, day 7, and day 10. The in vivo study was carried out by implanting PCL
      nanofibers and film scaffolds subcutaneously in rats to test the biocompatibility
      and host response at time points of week 1, week 2, and week 4. The in vitro
      studies revealed that the initial monocyte adhesion on the aligned fiber scaffold
      was significantly less (p < 0.001) when compared to the random fiber scaffold.
      The in vivo study showed that the thicknesses of fibrous capsule on fibrous
      scaffolds were 7.55 +/- 0.54 microm for aligned fibers and 4.13 +/- 0.31 microm
      for random fibers, which were significantly thinner than that of film implants
      37.7 +/- 0.25 microm (p < 0.001). Additionally, cell infiltration was observed in
      aligned fibrous scaffolds both in vitro and in vivo, while on random fibers and
      films, distinct fibrous capsule boundaries were found on the surfaces. These
      results indicate that aligned electrospun nanofibers may serve as a promising
      scaffold for tissue engineering by minimizing host response, enhancing tissue
      scaffold integration, and eliciting a thinner fibrous capsule.

PMID- 19768796
TI  - Porous hollow membrane sheet for tissue engineering applications.
AB  - In spite of the present advances in the scaffolds fabrication and bioreactor
      systems, the ability to create functional thick tissue masses in vitro is still a
      great tissue engineering challenge. To overcome this problem, the fabrication of
      a capillary bed, for nutrient supply to and waste product removal from the tissue
      engineering construct as it grows, is essential. However, the technical
      construction of a capillary-like architecture is complex and challenging. This
      study reports, for the very first time, a simple method to design and fabricate a
      porous hollow membrane sheet (PHMsh) to provide both a capillary bed and a
      scaffold to support tissue growth. The PHMsh composed of a flexible porous sheet
      involving parallel porous channels and can be used as flat-, rolled-, or
      sandwiched-shape scaffold. The PHMsh was fabricated from poly(epsilon
      caprolactone) polymer solution using solvent casting methods (i.e., immersion
      precipitation and air casting). Optical microscopy and scanning electron
      microscopy were used for the morphological analyses. The PHMsh was surface
      treated using n-hepthylamine plasma polymer (HApp) and X-ray photoelectron
      spectroscopy confirmed successful surface coating. Human umbilical vein
      endothelial cells (HUVECs) and fibroblast cells were used to evaluate the
      capability of PHMsh toward cell adhesion. The HApp coating enhanced both HUVEC
      and fibroblast cells adhesion. The obtained preliminary results demonstrated the
      successful fabrication of the PHMsh, with potential application for tissue
      engineering scaffolds, particularly in large tissue mass generation under
      perfusion systems in vitro, which is our future research direction.

PMID- 19768797
TI  - Decrease in as-needed sedative use by limiting nighttime sleep disruptions from
      hospital staff.
AB  - BACKGROUND: Hospital routines frequently interrupt nighttime sleep. Sedatives
      promote sleep, but increase the risk of delirium and falls. Few interventional
      trials have studied sleep promotion in medical-surgical units and little is known
      about its impact on sedative use. OBJECTIVE: To determine causes of sleep
      disruption, and assess whether decreasing sleep disruptions lowers sedative use
      in medical-surgical patients. DESIGN AND SETTING: Interventional trial with
      historical controls on a medical-surgical unit of a community teaching hospital.
      Nurses, physicians, and patients were blinded to the measurement of as-needed
      sedative use. PATIENTS: Consecutive eligible adults (n = 161 preintervention
      patients, n = 106 intervention patients). INTERVENTION: We developed the
      "Somerville Protocol," which included the establishment of an 8-hour "Quiet Time"
      that began with automated lights-off and lullaby; staff-monitored noise; and
      avoidance of waking of patients for routine vital signs and medications.
      MEASUREMENTS: As-needed sedative use, responses to a patient questionnaire, and
      responses to a modified Verran Snyder-Halpern (VSH) sleep scale. RESULTS:
      Preintervention, "hospital staff " was the disturbance most likely to keep
      patients awake. The intervention decreased the proportion of patients reporting
      it from 42% to 26%, a 38% reduction (P = 0.009; 95% confidence interval [CI]:
      0.0452-0.2765). Preintervention, 32% of patients received as-needed sedatives,
      compared to 16% with the intervention, a 49% reduction (P = 0.0041; 95% CI: 0.056
      0.26), with a 62% decrease in patients over age 64 years (P = 0.005). VSH scores
      were unchanged. CONCLUSIONS: Small modifications in hospital routines, especially
      in the timing of vital signs and routine medication administration, can
      significantly reduce sedative use in unselected hospital patients.

PMID- 19768798
TI  - Notch signaling: key role in intrauterine infection/inflammation, embryonic
      development, and white matter damage?
AB  - The mechanisms or pathophysiologies that lead to cerebral white matter damage
      during development are complex and not fully understood. It is postulated that
      exposure of the preterm brain to inflammatory cytokines during intrauterine
      infection/inflammation contributes to brain white matter damage, and this damage
      may affect the function and differentiation of progenitor oligodendrocyte cells
      under physiological conditions. The Notch pathway, an important signaling pathway
      controlling various cells' differentiation, functions in the timing of
      oligodendrocyte differentiation, and Notch signaling may contribute to white
      matter damage and may mediate neurogenesis in a pathophysiological phase. Recent
      studies have led to recognition of the role of the Notch pathway in neurogenesis
      in cerebral ischemic damage and in myelination and axonal damage of
      neurodegenerative diseases. Moreover, Notch plays a critical role in steering an
      immune response toward inflammation by regulating expression of various cytokines
      and proinflammatory cytokines resulting in the activation of Notch signaling.
      Thus, the Notch signaling pathway likely plays a key role in intrauterine
      infection/inflammation, brain development, and white matter damage, and future
      research directed toward understanding its role will be important. Insofar as
      Notch signaling could have an important effect on neurogenesis, mobilization of
      progenitor cells is one strategy for compensating for the neuronal losses seen in
      white matter damage after intrauterine infection/inflammation.

PMID- 19768799
TI  - Ultra scale-down approaches for clarification of mammalian cell culture broths in
      disc-stack centrifuges.
AB  - Ultra-scale down (USD) methodology developed by University College London for
      cell broth clarification with industrial centrifuges was applied to two common
      cell lines (NS0 and GS-CHO) expressing various therapeutic monoclonal antibodies.
      A number of centrifuges at various scales were used with shear devices operating
      either by high speed rotation or flow-through narrow channels. The USD
      methodology was found effective in accounting for both gravitational and shear
      effects on clarification performance with three continuous centrifuges at pilot
      and manufacturing scales. Different shear responses were observed with the two
      different cell lines and even with the same cell line expressing different
      products. Separate particle size analysis of the treated broths seems consistent
      with the shear results. Filterability of the centrifuged solutions was also
      evaluated to assess the utility of the USD approach for this part of the
      clarification operation.

PMID- 19768800
TI  - Structural model of rho1 GABAC receptor based on evolutionary analysis: Testing
      of predicted protein-protein interactions involved in receptor assembly and
      function.
AB  - The homopentameric rho1 GABA(C) receptor is a ligand-gated ion channel with a
      binding pocket for gamma-aminobutyric acid (GABA) at the interfaces of N-terminal
      extracellular domains. We combined evolutionary analysis, structural modeling,
      and experimental testing to study determinants of GABA(C) receptor assembly and
      channel gating. We estimated the posterior probability of selection pressure at
      amino acid residue sites measured as omega-values and built a comparative
      structural model, which identified several polar residues under strong selection
      pressure at the subunit interfaces that may form intersubunit hydrogen bonds or
      salt bridges. At three selected sites (R111, T151, and E55), mutations disrupting
      intersubunit interactions had strong effects on receptor folding, assembly, and
      function. We next examined the role of a predicted intersubunit salt bridge for
      residue pair R158-D204. The mutant R158D, where the positively charged residue is
      replaced by a negatively charged aspartate, yielded a partially degraded receptor
      and lacked membrane surface expression. The membrane surface expression was
      rescued by the double mutant R158D-D204R, where positive and negative charges are
      switched, although the mutant receptor was inactive. The single mutants R158A,
      D204R, and D204A exhibited diminished activities and altered kinetic profiles
      with fast recovery kinetics, suggesting that R158-D204 salt bridge perhaps
      stabilizes the open state of the GABA(C) receptor. Our results emphasize the
      functional importance of highly conserved polar residues at the protein-protein
      interfaces in GABA(C) rho1 receptors and demonstrate how the integration of
      computational and experimental approaches can aid discovery of functionally
      important interactions.

PMID- 19768801
TI  - NMR solution structures of actin depolymerizing factor homology domains.
AB  - Actin is one of the most conserved proteins in nature. Its assembly and
      disassembly are regulated by many proteins, including the family of actin
      depolymerizing factor homology (ADF-H) domains. ADF-H domains can be divided into
      five classes: ADF/cofilin, glia maturation factor (GMF), coactosin, twinfilin,
      and Abp1/drebrin. The best-characterized class is ADF/cofilin. The other four
      classes have drawn much less attention and very few structures have been
      reported. This study presents the solution NMR structure of the ADF-H domain of
      human HIP-55-drebrin-like protein, the first published structure of a drebrin
      like domain (mammalian), and the first published structure of GMF beta (mouse).
      We also determined the structures of mouse GMF gamma, the mouse coactosin-like
      domain and the C-terminal ADF-H domain of mouse twinfilin 1. Although the overall
      fold of the five domains is similar, some significant differences provide
      valuable insights into filamentous actin (F-actin) and globular actin (G-actin)
      binding, including the identification of binding residues on the long central
      helix. This long helix is stabilized by three or four residues. Notably, the F
      actin binding sites of mouse GMF beta and GMF gamma contain two additional beta
      strands not seen in other ADF-H structures. The G-actin binding site of the ADF-H
      domain of human HIP-55-drebrin-like protein is absent and distorted in mouse GMF
      beta and GMF gamma.

PMID- 19768802
TI  - Application of modeling and simulation tools for the evaluation of biocatalytic
      processes: a future perspective.
AB  - Modeling and simulation techniques have for some time been an important feature
      of biocatalysis research, often applied as a complement to experimental studies.
      In this short review, we report on the state-of-the-art process and kinetic
      modeling for biocatalysis with the aim of identifying future research needs. We
      have particularly focused on four aspects of modeling: (i) the model purpose,
      (ii) the process model boundary, (iii) the model structure, and (iv) the model
      identification procedure. First, one finds that most of the existing models
      describe biocatalyst behavior in terms of enzyme selectivity, mechanism, and
      reaction kinetics. More recently, work has focused on extending these models to
      obtain process flowsheet descriptions. Second, biocatalysis models remain at a
      relatively low level of complexity compared with the trends observed in other
      engineering disciplines. Hence, there is certainly room for additional
      development, i.e., detailed mixing and hydrodynamics, more process units (e.g.,
      biorefinery). Third, biocatalysis models have been only partially subjected to
      formal statistical analysis. In particular, uncertainty analysis is needed to
      ascertain reliability of the predictions of the process model, which is necessary
      to make sound engineering decisions (e.g., the optimal process flowsheet, control
      strategy, etc). In summary, for modeling studies to be more mature and
      successful, one needs to introduce Good Modeling Practice and that asks for (i) a
      standardized and systematic guideline for model development, (ii) formal
      identifiability analysis, and (iii) uncertainty analysis. This will advance the
      utility of models in biocatalysis for more rigorous application within process
      design, optimization, and control strategy evaluation.

PMID- 19768803
TI  - Development of an animal-component free medium for vero cells culture.
AB  - This work describes the development of an animal-component free medium (IPT-AFM)
      that allows an optimal growth of Vero cells, an adherent cell line used for the
      production of viral vaccines. Statistical experimental design was applied to
      identify crucial nutrients that affect cell growth. Using Medium 199 or MEM as a
      basal medium, a serum-free medium (SFM) referred as IPT-SFM that only enclosed
      transferrin as a component of animal origin was developed at first. Then, the
      composition of IPT-SFM was further improved to obtain an animal-component free
      medium named IPT-AFM. IPT-AFM contains M199 as a basal medium, plant
      hydrolysates, epidermal growth factor, ethanolamine, ferric citrate, and vitamin
      C. Among various plant hydrolysates, specific combinations of soy (Hypep 1510)
      and wheat gluten (Hypeps 4601 and 4605) hydrolysates, were identified to promote
      cell growth; whereas individual Hypeps had a minor positive effect on cell
      growth. Nevertheless, the removal of serum did influence cell attachment. Coating
      tissue-culture flasks with teleostean, a product extracted from cold water fish
      skin, had not only enhanced cell attachment but also improved cell growth
      performance in static cultures. Different non-animal proteases were also assessed
      as an alternative to trypsin. TrypLE Select, a recombinant trypsin, gave the best
      cell growth performances. Kinetics of cell growth in IPT-AFM were investigated in
      T-flasks, cell growth was comparable with that obtained in MEM+10% fetal calf
      serum (FCS). A mean cell division number equal to 2.26 +/- 0.18 and a specific
      growth rate micro 0.019 +/- 0.003 h(-1) were achieved in IPT-AFM.

PMID- 19768804
TI  - Recombinant human DNase in children with airway malacia and lower respiratory
      tract infection.
AB  - BACKGROUND: Children with airway malacia often have protracted courses of airway
      infections, because dynamic airway collapse during coughing results in impaired
      mucociliary clearance. The aim of this study was to determine the effect of the
      mucolytic drug recombinant human deoxyribonuclease (rhDNase) on the recovery of
      respiratory symptoms in children with airway malacia and lower respiratory tract
      infection (LRTI). METHODS: In a randomized double-blind controlled clinical
      trial, 40 children with airway malacia and LRTI were randomly assigned to receive
      either 2.5 mg nebulized rhDNase or placebo twice daily for 2 weeks. The primary
      endpoint was the change in the cough diary score (CDS) (scale 0-5) from baseline
      to the second week of treatment. Secondary endpoints were VAS symptom scores for
      cough, dyspnea, and difficulty in expectorating sputum, need for an antibiotic
      course, and lung function data (FVC, FEV(1), FEF(75), R(int(e))). RESULTS: There
      was no significant difference in the mean change in CDSs from baseline between
      the rhDNase group and the placebo group (mean difference for daytime 0.19 (95% CI
      -0.53 to 0.90); for nighttime 0.38 (95% CI -0.30 to 1.05). Proportions of
      patients requiring antibiotics, and the mean changes in symptom scores and lung
      function from baseline did not significantly differ between both groups.
      CONCLUSION: Treatment with 2 weeks of nebulized rhDNase does not enhance recovery
      or reduce the need for antibiotics in children with airway malacia and LRTI.
      (Controlled-trials.com number, ISRCTN85366144).

PMID- 19768805
TI  - Respiratory health in overweight and obese Chinese children.
AB  - OBJECTIVES: Childhood obesity has been suggested to be associated with asthma and
      impairment of pulmonary functions, but the findings are conflicting. The aim of
      this study was to examine the relationship of body mass index (BMI) with asthma,
      asthma-like symptoms, and lung functions in Chinese schoolchildren. METHODS: Data
      from a survey of 2,179 children aged 10.04 +/- 0.85 years in Guangzhou, China
      were analyzed. Children's history of respiratory symptoms/diseases and other
      potential confounders were obtained by standardized questionnaires.
      Anthropometric and spirometry tests were performed in all subjects. Children were
      categorized as "normal weight," "overweight," and "obesity" using Chinese Obesity
      cut-off points based on age- and gender-specific BMI values. RESULTS: Being
      overweight was significantly associated with an increased risk of cough with cold
      (odds ratio, OR 1.60; 95% CI 1.01-2.55) in boys, and phlegm with cold (OR 2.46;
      95% CI 1.25-4.85) and cough without cold (OR 2.91; 95% CI 1.05-8.08) in girls.
      Being obese was positively associated with an increased risk of phlegm with cold
      (OR 1.69; 95% CI 1.04-2.87) in boys, and wheezing (OR 3.82; 95% CI 1.28-11.42)
      and wheezing with cold in girls (OR 8.75; 95% CI 2.11-36.34). The forced vital
      capacity (FVC) increased with BMI in all children, overweight boys and obese
      girls also had significantly higher forced expiratory volume in 1 sec (FEV(1))
      than those with normal weight. CONCLUSIONS: Our findings demonstrate that
      overweight and obesity are high risks for children's respiratory symptoms and
      diseases. Pulmonary function was not adversely affected by obesity in
      schoolchildren.

PMID- 19768806
TI  - Healthcare expenditures for privately insured people with cystic fibrosis.
AB  - With improved survival and new therapies for people with cystic fibrosis (CF),
      updated information on medical care expenditures for those individuals is needed.
      We estimated medical care expenditures, including both insurance reimbursements
      and patient out-of-pocket expenses, for privately insured people with CF and
      investigated how those expenditures varied with certain complications of CF. From
      a private insurance claims database of people covered by health plans associated
      with large corporate employers, we identified people with CF who were currently
      receiving medical care for the disorder and characterized their medical
      expenditures during the period 2004-2006. We selected a matching group of people
      who did not have CF based on age, sex, and geographic area, and calculated
      incremental expenditures associated with CF. We also examined the effect of age
      and certain complications of CF on these expenditures. The annual medical care
      expenditure for a person with actively managed CF averaged $48,098 in 2006
      dollars, which was 22 times higher than for a person without CF. This ratio is
      high relative to other chronic disorders. Outpatient prescription medications
      made up the largest component of total expenditures for people with CF (39%).
      Those who were recorded in claims data as having a liver or lung transplant,
      malnutrition, diabetes, or a chronic Pseudomonas aeruginosa pulmonary infection
      incurred much higher expenditures than people without these conditions. People
      with CF will incur high medical expenditures throughout their lifespan. These
      findings will assist in the development of economic evaluations of future CF
      screening and management initiatives.

PMID- 19768807
TI  - Pulmonary function changes in children after transcatheter closure of atrial
      septal defect.
AB  - This study was performed to assess changes in pulmonary function test (PFT) and
      pulmonary outcome after transcatheter closure of atrial septal defect (ASD) in
      pediatric patients. A total 55 pediatric patients undergoing transcatheter ASD
      closure received PFT at baseline (day before ASD closure), and at 3 days and 6
      months after procedure. Forced vital capacity (FVC), forced expired volume in 1
      sec (FEV(1)), FEV(1) to FVC ratio (FEV(1)/FVC), peak expiratory flow (PEF), and
      mean forced expiratory flow during the middle half of FVC (FEF(25-75)) were
      measured. Individually, subjects were classified by spirometry as normal,
      obstructive or restrictive, to evaluate the effect of transcatheter closure on
      pulmonary outcome. These 55 children had significantly reduced mean PEF and
      FEF(25-75) (84 +/- 24%, P = 0.040 and 76 +/- 22%, P = 0.010, respectively) at
      baseline, with FEF(25-75) reduced significantly at 3 days and 6 months (78 +/-
      24%, P = 0.010 and 81 +/- 24%, P = 0.040, respectively) after transcatheter
      closure. Six months after transcatheter closure of ASD, significant improvement
      was observed in mean FVC (94 +/- 19% vs. 98 +/- 15%, P = 0.034) and FEV(1) (90 +/
      20% vs. 96 +/- 19%, P = 0.008). Assessed individually, better pulmonary outcome
      was found in patients without pulmonary hypertension (PH) (chi(2) = 8.333, P =
      0.044). PFT disturbance was observed in significant flow limitation in the
      peripheral airway of ASD patients. Improved PFT was found after transcatheter
      closure and better pulmonary outcome was observed in patients without PH. ASD
      children need monitoring pulmonary function and should receive transcatheter
      closure before PH develops.

PMID- 19768808
TI  - Controllable protein cleavages through intein fragment complementation.
AB  - Intein-based protein cleavages, if carried out in a controllable way, can be
      useful tools of recombinant protein purification, ligation, and cyclization.
      However, existing methods using contiguous inteins were often complicated by
      spontaneous cleavages, which could severely reduce the yield of the desired
      protein product. Here we demonstrate a new method of controllable cleavages
      without any spontaneous cleavage, using an artificial S1 split-intein consisting
      of an 11-aa N-intein (I(N)) and a 144-aa C-intein (I(C)). In a C-cleavage design,
      the I(C) sequence was embedded in a recombinant precursor protein, and the small
      I(N) was used as a synthetic peptide to trigger a cleavage at the C-terminus of
      I(C). In an N-cleavage design, the short I(N) sequence was embedded in a
      recombinant precursor protein, and the separately produced I(C) protein was used
      to catalyze a cleavage at the N-terminus of I(N). These N- and C-cleavages showed
      >95% efficiency, and both successfully avoided any spontaneous cleavage during
      expression and purification of the precursor proteins. The N-cleavage design also
      revealed an unexpected and interesting structural flexibility of the I(C)
      protein. These findings significantly expand the effectiveness of intein-based
      protein cleavages, and they also reveal important insights of intein structural
      flexibility and fragment complementation.

PMID- 19768809
TI  - KING (Kinemage, Next Generation): a versatile interactive molecular and
      scientific visualization program.
AB  - Proper visualization of scientific data is important for understanding spatial
      relationships. Particularly in the field of structural biology, where researchers
      seek to gain an understanding of the structure and function of biological
      macromolecules, it is important to have access to visualization programs which
      are fast, flexible, and customizable. We present KiNG, a Java program for
      visualizing scientific data, with a focus on macromolecular visualization. KiNG
      uses the kinemage graphics format, which is tuned for macromolecular structures,
      but is also ideal for many other kinds of spatially embedded information. KiNG is
      written in cross-platform, open-source Java code, and can be extended by end
      users through simple or elaborate "plug-in" modules. Here, we present three such
      applications of KiNG to problems in structural biology (protein backbone
      rebuilding), bioinformatics of high-dimensional data (e.g., protein sidechain chi
      angles), and classroom education (molecular illustration). KiNG is a mature
      platform for rapidly creating and capitalizing on scientific visualizations. As a
      research tool, it is invaluable as a test bed for new methods of visualizing
      scientific data and information. It is also a powerful presentation tool, whether
      for structure browsing, teaching, direct 3D display on the web, or as a method
      for creating pictures and videos for publications. KiNG is freely available for
      download at http://kinemage.biochem.duke.edu.

PMID- 19768811
TI  - MDMA-evoked changes in the binding of dopamine D(2) receptor ligands in striatum
      of rats with unilateral serotonin depletion.
AB  - We earlier reported an anomalous 50% decrease in [(11)C]N-methylspiperone
      ([(11)C]NMSP) binding to dopamine D(2)-like receptors in living pig striatum
      after challenge with 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy"),
      suggesting either (1) a species peculiarity in the vulnerability of butyrophenone
      binding to competition from dopamine or (2) a novel consequence of synergistic
      actions of serotonin and dopamine at dopamine receptors. To distinguish these
      possibilities, we used microPET to test the vulnerability of [(11)C]NMSP binding
      in striatum of rats with unilateral telencephalic serotonin lesions, later
      verified by [(125)I]RTI-55 autoradiography. Baseline [(11)C]NMSP microPET
      recordings were followed by either saline or MDMA-HCl (4 mg/kg) injections
      (i.v.), and a second [(11)C]NMSP recording, culminating with injection of
      [(3)H]raclopride for autoradiography ex vivo. Neither MDMA-challenge nor
      serotonin lesion had any detectable effect on [(11)C]NMSP binding. In contrast,
      MDMA challenge increased receptor occupancy by [(3)H]raclopride ex vivo (relative
      to the B(max) in vitro) from 8% to 12%, and doubled the free ligand concentration
      in cerebral cortex, apparently by blocking hepatic CYP2D6. Assuming a single
      binding-site model, the increased [(3)H]raclopride binding indicated doubling of
      the apparent equilibrium dissociation constant in vivo (K(app) (d)), revealing a
      2-fold increase in competition from endogenous dopamine at [(3)H]raclopride
      binding sites. The results favor hypothesis (1) that the remarkable vulnerability
      of [(11)C]NMSP binding in pig striatum to MDMA challenge does not generalize to
      the rodent.

PMID- 19768812
TI  - [Gly(14)]-humanin rescues long-term potentiation from amyloid beta protein
      induced impairment in the rat hippocampal CA1 region in vivo.
AB  - The novel neuroprotective action of Humanin (HN), especially its derivative
      [Gly(14)]-humanin (HNG), against Alzheimer's disease (AD)-related insults has
      been reported. However, it is still short of electrophysiological evidence for
      the protection of HN on synaptic plasticity, and the molecular mechanisms that
      underlie the neuroprotective function of HN remain largely unknown. The present
      study examined the effects of intracerebroventricular (i.c.v.) injection of HNG
      on amyloid beta (Abeta), a main constituent of senile plaques in the AD brain,
      induced suppression of long-term potentiation (LTP) in the rat hippocampal CA1
      region in vivo and investigated the possible mechanism of HNG in LTP protection.
      We found that application of Abeta fragments 25-35 (Abeta25-35) and 31-35
      (Abeta31-35) significantly inhibited high frequency stimulation-induced LTP,
      while HNG effectively prevented the suppression of LTP induced by Abeta fragments
      in a dose-dependent manner. After pretreatment with Genistein, a tyrosine kinase
      inhibitor, the protective action of HNG on LTP was nearly completely abolished.
      Therefore, the present study demonstrated for the first time that HNG could
      protect against the neurotoxic Abeta-induced hippocampal LTP impairment and the
      tyrosine kinase pathway was involved in the neuroprotective action of HNG,
      suggesting that HNG might be one of the promising candidates for the treatment of
      AD in the future.

PMID- 19768810
TI  - The crystal structure of the AF2331 protein from Archaeoglobus fulgidus DSM 4304
      forms an unusual interdigitated dimer with a new type of alpha + beta fold.
AB  - The structure of AF2331, a 11-kDa orphan protein of unknown function from
      Archaeoglobus fulgidus, was solved by Se-Met MAD to 2.4 A resolution. The
      structure consists of an alpha + beta fold formed by an unusual homodimer, where
      the two core beta-sheets are interdigitated, containing strands alternating from
      both subunits. The decrease in solvent-accessible surface area upon dimerization
      is unusually large (3960 A(2)) for a protein of its size. The percentage of the
      total surface area buried in the interface (41.1%) is one of the largest observed
      in a nonredundant set of homodimers in the PDB and is above the mean for nearly
      all other types of homo-oligomers. AF2331 has no sequence homologs, and no
      structure similar to AF2331 could be found in the PDB using the CE, TM-align,
      DALI, or SSM packages. The protein has been identified in Pfam 23.0 as the
      archetype of a new superfamily and is topologically dissimilar to all other
      proteins with the "3-Layer (BBA) Sandwich" fold in CATH. Therefore, we propose
      that AF2331 forms a novel alpha + beta fold. AF2331 contains multiple negatively
      charged surface clusters and is located on the same operon as the basic protein
      AF2330. We hypothesize that AF2331 and AF2330 may form a charge-stabilized
      complex in vivo, though the role of the negatively charged surface clusters is
      not clear.

PMID- 19768813
TI  - A nonsynonymous polymorphism in cannabinoid CB2 receptor gene is associated with
      eating disorders in humans and food intake is modified in mice by its ligands.
AB  - Marijuana use activates cannabinoid receptors (CB-Rs) producing several
      behavioral effects related to addiction, mood, and appetite. We investigated the
      association between CNR2 gene, which encodes cannabinoid CB2 receptor (CB2-R) and
      eating disorders in 204 subjects with eating disorders and 1876 healthy
      volunteers in Japanese population. The effect of treatment with CB2-R ligands on
      mouse food consumption was also determined. The CB2-R ligands used suppressed
      food intake in a time- and strain-dependent manner when food was available ad
      libitum and during the 12-h fast except, AM 630-the CB2-R antagonist that
      stimulated food consumption in food-deprived mice. There is an association
      between the R63Q polymorphism of the CNR2 gene and eating disorders (P = 0.04;
      Odds ratio 1.24, 95% CI, (1.01-1.53). These results suggest that cannabinoid CB2
      R is involved in the endocannabinoid signaling mechanisms associated with the
      regulation of food intake and in eating disorders.

PMID- 19768814
TI  - Idiopathic REM sleep behavior disorder in the transition to degenerative disease.
AB  - Idiopathic REM sleep behavior disorder (RBD) predicts Parkinson's disease (PD)
      and dementia. However, the nature of the disease that emerges from RBD has not
      been fully characterized. Since 2004, we have been conducting a prospective study
      of idiopathic RBD patients, providing an opportunity to directly observe patients
      as they transitioned to a defined neurodegenerative syndrome. Patients with
      idiopathic RBD underwent an extensive annual evaluation of motor function,
      olfaction, color vision, autonomic function, cognition and psychiatric symptoms.
      Neurodegenerative disease was defined according to standard criteria. We compared
      these measures in patients who had developed PD to those with dementia, all
      within the first year of developing disease. Of 67 patients, 6 developed PD and
      eleven developed dementia. Except for cognitive functioning, all tests of
      olfaction, color vision, autonomic function, depression, and quantitative
      measures of motor speed were similar in patients with PD and dementia. Of
      dementia patients, seven met criteria for probable Lewy body dementia (LBD) and
      four for Alzheimer's disease (or, possible LBD). In all probable LBD cases, the
      diagnosis was made because of parkinsonism, with no patient experiencing
      hallucinations or fluctuations. Patients with "Alzheimer's disease" seemed to
      have LBD, as they demonstrated typical LBD cognitive profiles on
      neuropsychological testing and were indistinguishable from LBD patients in
      ancillary measures. Therefore, among RBD patients with new-onset LBD,
      hallucinations or fluctuations are absent, suggesting that RBD is a reliable
      early sign of LBD. The indistinguishability of dementia and PD in all ancillary
      measures suggests a single unitary "RBD-then-neurodegeneration" process, the
      clinical presentation of which depends upon selective neuronal vulnerability.

PMID- 19768815
TI  - Loss of nocturnal blood pressure fall in various extrapyramidal syndromes.
AB  - Cardiovascular autonomic dysfunction has frequently been reported in some
      patients with extrapyramidal syndromes, especially multiple system atrophy (MSA)
      but also Parkinson's disease (PD). However, there are only few reports on the
      prevalence of cardiovascular autonomic dysfunction progressive in supranuclear
      palsy (PSP). Moreover, the relation of detailed cardiovascular testing and easy
      to assess 24-hour ambulatory blood pressure (BP) is not known. Our study
      evaluates 24-hour ambulatory BP monitoring in patients with PD, PSP, MSA, and
      corresponding controls (Con) and relates the findings to the results of
      comprehensive cardiovascular autonomic testing. Twenty-three patients with PD, 25
      patients with PSP, 25 patients with MSA, and 26 corresponding controls were
      studied by 24-hour ambulatory BP monitoring (ABPM) in comparison to
      cardiovascular autonomic testing. Patients with PD, PSP, and MSA presented
      frequently with a pathological nocturnal BP regulation (no decrease or even an
      increase of nocturnal BP) in comparison to the control group (PD 48%, PSP 40%,
      MSA 68% vs. Con 8%). In MSA and PD patients, the frequent pathological BP
      increase during night was closely correlated to orthostatic hypotension. Since
      loss of nocturnal BP fall is frequent in patients with extrapyramidal syndromes,
      even if they are free of subjective autonomic dysfunction, we recommend 24-hour
      ABPM as an easy to perform screening test, especially if detailed autonomic
      testing is not available. Pathological loss of nocturnal BP fall may account for
      increased cardiovascular mortality in extrapyramidal syndromes.

PMID- 19768816
TI  - A two-photon tracer for glucose uptake.

PMID- 19768817
TI  - Poly(2-oxazoline)s: a polymer class with numerous potential applications.
AB  - The living cationic ring-opening polymerization of 2-oxazolines has been studied
      in great detail since its discovery in 1966. The versatility of this living
      polymerization method allows copolymerization of a variety of 2-oxazoline
      monomers to give a range of tunable polymer properties that enable, for example,
      hydrophilic, hydrophobic, fluorophilic, as well as hard and soft materials to be
      obtained. However, this class of polymers was almost forgotten in the 1980s and
      1990s because of their long reaction times and limited application possibilities.
      In the new millennium, a revival of poly(2-oxazoline)s has arisen because of
      their potential use as biomaterials and thermoresponsive materials, as well as
      the easy access to defined amphiphilic structures for (hierarchical) self
      assembly. Recent developments that illustrate the potential of poly(2-oxazoline)s
      are discussed in this Review. In addition, the promising combination of poly(2
      oxazoline)s and click chemistry is illustrated.

PMID- 19768818
TI  - Modulating electronic interactions between closely spaced complementary pi
      surfaces with different outcomes: regio- and diastereomerically pure
      subphthalocyanine-C60 tris adducts.

PMID- 19768819
TI  - Fast prediction of selectivity in heterogeneous catalysis from extended Bronsted
      Evans-Polanyi relations: a theoretical insight.

PMID- 19768820
TI  - Catalytic enantioselective stereoablative alkylation of 3-halooxindoles: facile
      access to oxindoles with C3 all-carbon quaternary stereocenters.

PMID- 19768821
TI  - Tantalum-doped titanium dioxide nanowire arrays for dye-sensitized solar cells
      with high open-circuit voltage.

PMID- 19768822
TI  - Gold catalysis: isolation of vinylgold complexes derived from alkynes.

PMID- 19768823
TI  - Fast ion-transfer processes at nanoscopic liquid/liquid interfaces.

PMID- 19768824
TI  - Entirely artificial signal transduction with a primary messenger.

PMID- 19768825
TI  - Resolving the atomic structure of vanadia monolayer catalysts: monomers, trimers,
      and oligomers on ceria.

PMID- 19768826
TI  - O-O bond activation in heterobimetallic peroxides: synthesis of the peroxide
      [LNi(mu,eta2:eta2-O2)K] and its conversion into a bis(mu-hydroxo) nickel zinc
      complex.

PMID- 19768827
TI  - A formal carbon-sulfur triple bond: H-C[triple bond]S-O-H.

PMID- 19768828
TI  - Mapping the landscape of potentially primordial informational oligomers: oligo
      dipeptides tagged with orotic acid derivatives as recognition elements.

PMID- 19768829
TI  - Nitro-substituted aryl lithium compounds in microreactor synthesis: switch
      between kinetic and thermodynamic control.

PMID- 19768830
TI  - Asymmetric synthesis of beta-alkynyl aldehydes by rhodium-catalyzed conjugate
      alkynylation.

PMID- 19768831
TI  - A cineradiographic study of lung ventilation in Alligator mississippiensis.
AB  - The skeletal and visceral kinematics of lung ventilation of the American
      alligator (Alligator mississippiensis) was examined using cineradiography,
      pneumotachometry, and intrapulmonary pressure recording. The respiratory pattern
      of A. mississippiensis is intermittent and diphasic. The inspiratory lung volume
      is retained during the non-ventilatory period through closure of the glottis. The
      aspiration pump of A. mississippiensis consists of multiple components: visceral
      movement, pubic rotation, gastralial movement, and costosternal movement, which
      vary independently in their contribution to lung ventilation. Vertebral flexion
      and extension is also observed, and may be a passive artifact of costal
      displacement. The amount of craniocaudal visceral movement during lung
      ventilation is variable, and can produce as much as 60% of the tidal volume.
      Pubic rotation is not directly coupled to visceral movement and contributes a
      relatively small percentage of the tidal volume, approximately 4% on average, as
      does vertebral flexion, which contributes less than 3%. Costosternal movement
      contributes the remaining majority of tidal volume, generally over 40%. The
      gastralia stiffen the abdominal wall and likely facilitate unified displacement
      of the abdominal wall. Tripartite ribs facilitate thoracic movement, allowing
      substantial excursion of the body wall. A relatively abrupt change in position of
      the vertebral parapophysis in the anterior thorax results in an increase in
      lateral rib movement in the posterior half of the thorax. The crocodylian
      aspiration pump appears to consist of a derived pelvic and diaphragmatic
      breathing pump combined with a basal costosternal and gastralial aspiration pump.

PMID- 19768833
TI  - Abstracts of the 82nd Annual Meeting of the Japanese Pharmacological Society,
      March 16-18, 2009, Yokohama, Japan.

PMID- 19768832
TI  - Nucleation capacity and presence of centrioles define a distinct category of
      centrosome abnormalities that induces multipolar mitoses in cancer cells.
AB  - Analysis of centrosome number and structure has become one means of assessing the
      potential for aberrant chromosome segregation and aneuploidy in tumor cells.
      Centrosome amplification directly causes multipolar catastrophic mitoses in mouse
      embryonic fibroblasts (MEFs) deficient for the tumor suppressor genes Brca1 or
      Trp53. We observed supernumerary centrosomes in cell lines established from
      aneuploid, but not from diploid, colorectal carcinomas; however, multipolar
      mitoses were never observed. This discrepancy prompted us to thoroughly
      characterize the centrosome abnormalities in these and other cancer cell lines
      with respect to both structure and function. The most striking result was that
      supernumerary centrosomes in aneuploid colorectal cancer cell lines were unable
      to nucleate microtubules, despite the presence of gamma-tubulin, pericentrin,
      PLK1, and AURKA. Analysis by scanning electron microscopy revealed that these
      supernumerary structures are devoid of centrioles, a result significantly
      different from observations in aneuploid pancreatic cancer cell lines and in
      Trp53 or Brca1 deficient MEFs. Thus, multipolar mitoses are dependent upon the
      ability of extra gamma-tubulin containing structures to nucleate microtubules,
      and this correlated with the presence of centrioles. The assessment of centrosome
      function with respect to chromosome segregation must therefore take into
      consideration the presence of centrioles and the capacity to nucleate
      microtubules. The patterns and mechanisms of chromosomal aberrations in
      hematologic malignancies and solid tumors are fundamentally different. The former
      is characterized by specific chromosome translocations, whose consequence is the
      activation of oncogenes. Most carcinomas, however, reveal variations in the
      nuclear DNA content. The observed genomic imbalances and gross variations in
      chromosome number can result from unequal chromosome segregation during mitotic
      cell division. It is therefore fundamental to elucidate mechanisms involved in
      distribution of the genome to daughter cells. Prior to cell division, the
      centrosome organizes microtubules and the mitotic spindle. Deciphering the
      consequences of alterations in centrosome number, structure, and function is an
      important step towards understanding how a diploid genome is maintained. Although
      extra centrosomes have now been observed in carcinomas and were correlated with
      aneuploidy, a careful functional investigation of these structures and their role
      in generating chromosome imbalances may lead to the identification of distinct
      mechanistic pathways of genomic instability. Understanding these pathways will
      also be important in determining whether they are potential molecular targets of
      therapeutic intervention.

PMID- 19768834
TI  - Older athletes put their ankles at risk.  It's tempting to dismiss ankle injuries
      as minor, but if tendons are damaged pain can become chronic.

PMID- 19768835
TI  - Hold the beef, live longer.  Eleven and 16 percent of deaths in men and women,
      respectively, could be prevented if red meat intake decreased.  Global impact
      also cited.

PMID- 19768836
TI  - A new kind of "silent" heart attack.  It's as deadly as a symptomatic heart
      attack--but this kind is not visible on an electrocardiogram.

PMID- 19768837
TI  - Combination therapy can help reduce pain and depression.  When these conditions
      coexist, antidepressants and pain self-management can improve symptoms.

PMID- 19768838
TI  - Is psoriasis a skin disease or a form of arthritis?

PMID- 19768840
TI  - What can you tell me about Mohs surgery for skin cancer?

PMID- 19768839
TI  - Is it true that gum disease could put me at risk for heart disease?

PMID- 19768841
TI  - The quality of medical advice in low-income countries.

PMID- 19768842
TI  - Are we finally winning the war on cancer?

PMID- 19768843
TI  - Providing prescription drug coverage to the elderly: America's experiment with
      Medicare Part D.

PMID- 19768844
TI  - Technology. Hospital pushes digital envelope, lets patients control records.

PMID- 19768845
TI  - Patient care. Hospitals turning to 24/7 cardiac teams to hasten care.

PMID- 19768846
TI  - [A conference in China on private health care in low income countries].

PMID- 19768847
TI  - Postgraduate medical entrance system needs reform.

PMID- 19768848
TI  - Mechanism of scavenging action of N-acetylcysteine for the OH radical: a quantum
      computational study.
AB  - N-Acetylcysteine, a precursor of glutathione, is an effective antioxidant present
      in biological systems. The mechanism of scavenging action of N-acetylcysteine for
      the OH radical was studied theoretically. For this purpose, reactions of the OH
      radical at the different sites of N-acetylcysteine were investigated. All the
      relevant extrema on the potential energy surfaces were located by optimizing the
      geometries of the reactant and product complexes as well as those of the
      transition states at the BHandHLYP/AUG-cc-pVDZ level of density functional theory
      in the gas phase. The solvent effect of aqueous media was treated by performing
      single point energy calculations at the BHandHLYP/AUG-cc-pVDZ and MP2/AUG-cc-pVDZ
      levels of theory employing the polarizable continuum model. Correction for basis
      set superposition error (BSSE) was made by the counterpoise method. Rate
      constants for all the reaction mechanisms were calculated including the tunneling
      contributions. Our calculations show that the hydrogen atom of the SH group of N
      acetylcysteine would be most efficiently abstracted by the OH group, which is in
      agreement with experimental observations.

PMID- 19768850
TI  - Mollies down under: cross-dressing and Australian masculinity in Peter Carey's
      True history of the Kelly Gang.

PMID- 19768851
TI  - A snapshot of U.S. physicians: key findings from the 2008 Health Tracking
      Physician Survey.
AB  - This Data Bulletin presents findings from the Center for Studying Health System
      Change (HSC) 2008 Health Tracking Physician Survey, a nationally representative
      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 physicians, and the response rate was 62 percent. Estimates from this
      survey should not be compared to estimates from HSC's previous Community Tracking
      Study (CTS) Physician Surveys because of changes in the survey administration
      mode from telephone to mail, question wording, skip patterns, sample structure
      and population represented. More detailed information on survey content and
      methodology can be found at www.hschange.org.

PMID- 19768852
TI  - Medieval Arab lesbians and lesbian-like women.

PMID- 19768853
TI  - Assessing the need for on-site eye care professionals in community health
      centers.
AB  - Poor vision health severely impacts school and work performance, quality of life,
      and life expectancy, and results in billions of dollars in medical expenditures
      each year. While eye and vision problems are often associated with age, low
      income and racial and ethnic minorities also have elevated risk of eye problems.
      Federally-funded community health centers, which are mandated to provide
      comprehensive primary care in underserved communities, are often the only option
      to improve vision health for low-income residents. With respect to certain
      chronic conditions, health centers are able to provide high quality care that
      meets or exceeds national benchmarks despite limited financial resources, a
      shortage of primary care providers, and greater health care demands. What is not
      well known, is the extent to which health centers are able to provide on-site
      professional vision care. Our analysis found that seven out of 10 health centers
      do not staff on-site eye care professionals to provide comprehensive eye exams.
      Rather, many health centers rely on referral arrangements with local optometrists
      and ophthalmologists for such services. Major barriers to providing on-site
      comprehensive eye care services include the inability to afford necessary
      space/equipment and the perceived lack of reimbursement or inadequate
      reimbursement from Medicaid, Medicare and private insurers. Health centers
      indicated also that they also need assistance in developing a business plan,
      designing space, and developing an inventory of eye care equipment. While the
      lack of health insurance coverage, differences in Medicaid coverage and benefits
      across states, and inadequate reimbursements are likely to limit capacity and
      access to vision care professionals, another challenge may be patient's general
      lack of understanding about the need for routine eye exams. Therefore, strategies
      to improve access to vision care must go beyond developing financial incentives
      and restoring eye care professionals for eligible placements in underserved
      communities, to include education about the importance of routine eye care exams.

PMID- 19768854
TI  - Women, the family, and the fate of the nation in American anti-Catholic
      narratives, 1830-1860.

PMID- 19768855
TI  - Code of practice to help farmers keep their pigs free of influenza.

PMID- 19768856
TI  - Faith, desire, and sexual identity: Constance Maynard's Atonement for passion.

PMID- 19768857
TI  - The queer histories of a crime: representations and narratives of Leopold and
      Loeb.

PMID- 19768858
TI  - Bubbling over: soda consumption and its link to obesity in California.
AB  - Background The prevalence of overweight and obesity has increased dramatically in
      both adults and children in the last three decades in the n California, 62% of
      adolescents ages 12-17 and 41% of children ages 2-11 drink at least one soda or
      other sweetened beverage every day. In addition, 24% of adults drink at least one
      soda or other sweetened beverage on an average day. Adults who drink soda
      occasionally (not every day) are 15% more likely to be overweight or obese, and
      adults who drink one or more sodas per day are 27% more likely to be overweight
      or obese than adults who do not drink soda, even when adjusting for poverty
      status and race/ethnicity. This policy brief, produced collaboratively by the
      California Center for Public Health Advocacy and the UCLA Center for Health
      Policy Research, examines soda consumption in California by cities and counties
      using data from the 2005 California Health Interview Survey (CHIS 2005). In
      addition, the brief investigates whether there is an association between soda
      consumption and the prevalence of overweight and obesity. There are major
      differences in soda consumption rates by geographic area in California,
      suggesting that social and environmental factors affect the consumption of soda.
      Also, the prevalence of overweight and obesity is higher among those who drink
      one or more sodas or other sweetened beverages every day than among those who do
      not consume these soft drinks. Establishing public policies that focus on
      reducing soda consumption could contribute to reversing California's increasing
      overweight and obesity problem.

PMID- 19768859
TI  - The efficiency of induction of mutations by hydroxylamine.
AB  - Treatment of poly C with methoxyamine leads to formation of 5,6-dihydro-6
      methoxyaminocytosine residues in the polymer. These direct incorporation of
      adenylate residues into the poly G synthesized when the modified poly C is used
      as a template for RNA polymerase. The process is analogous to that of
      hydroxylamine-induced errors in replication. Comparison of the uptake of
      [14C]methoxyamine by the poly C with the percentage of adenylate incorporated in
      the poly G shows that the induction of errors is a highly efficient process:
      every modified cytosine residue directs the incorporation of one adenylate
      residue. A probable explanation for this is that the incorporation is mediated by
      hydrogen-bonding between the adenine and a predominant imino tautomer of the
      cytosine adduct.

PMID- 19768861
TI  - Three complementation groups in bacteriophage R17.
AB  - Complementation between amber mutants of R17 reveals the existence of three phage
      cistrons, designated A, B and C. Cistron A specifies a protein necessary for the
      synthesis of infective phage particles; cistron B specifies phage coat protein;
      and cistron C codes for phage-specific RNA synthetase. One of the mutants of
      group B is a polar coat-protein mutant, unable to synthesize either phage coat
      protein or RNA synthetase. Two models for polarity based on the interaction
      between ribosomes and the phage message during protein synthesis are discussed.

PMID- 19768860
TI  - Intact ribonucleic acid from defective particles of bacteriophage R17.
AB  - The growth of one group of amber mutants of R17 (class A) in non-permissive hosts
      results in a burst of bacteriophage-like particles, which are defective in that
      they are non-infectious. Here studies of particles produced by the growth of wild
      type R17 and four class A mutants on AB301, a non-permissive Hfr Escherichia coli
      strain, and on RNase(-)10, an RNase I-deficient derivative of AB301, are
      described. Defective particles grown on AB301 contain degraded, non-infectious
      RNA and are on the average less dense than wild-type phage; particles grown on
      RNase(-)10 contain intact, infectious RNA and exhibit normal density in cesium
      chloride gradients, but are nonetheless non-infectious as phage. In addition, the
      RNA in purified defective particles grown on RNase(-)10 is partially susceptible
      to nuclease attack, whereas RNA in wild-type phage is not. The studies
      demonstrate that the presence of degraded RNA in defective particles of R17
      results from the action of RNase I during the purification of the particles. The
      possible function of the A protein of R17 is considered in the light of the
      results obtained.

PMID- 19768862
TI  - The coding properties of methyl-deficient leucyl-transfer RNA.
AB  - Escherichia coli 58-161, a methionine auxotroph with "relaxed control",
      synthesizes methyl-deficient transfer RNA (tRNA) when subjected to methionine
      deprivation. Whereas [14C]leucyl-tRNA from normally grown bacteria fractionates
      into two peaks (I and II) on methylated albumin-kieselguhr columns, methyl
      deficient [14C]leucyl-tRNA shows an additional component (peak III). A ribosome
      binding assay shows a marked difference in the coding response to poly UC and
      poly UG between normal and methyl-deficient [14C]leucyl-tRNA. Compared to normal
      E. coli 58-161 [14C]leucyl-tRNA, the leucine-tRNA isolated from methionine
      deprived cells, manifests a twofold increase in poly UG response and a fivefold
      increase in poly UC response. Chromatography on methylated albumin-kieselguhr
      columns localized the increase in poly UG reactive tRNA to peak II. The
      chromatographic component of leucyl-tRNA characteristic of methyl-deficiency
      (peak III) responded exclusively to poly UC. These results are discussed in terms
      of a possible requirement for methylated bases in tRNA for specific codon
      recognition.

PMID- 19768863
TI  - Quaternary structure of Limnodrilus haemoglobin.
AB  - Structure of the haemoglobin from Limnodrilus gotoi (molecular weight, 3.01 x
      10(6)) was studied electron microscopically and chemically. The molecule appears
      to be a regular hexagonal cylinder having the dimensions 220 A x 160 A, and to
      consist of 12 identical submultiples arranged six and six into two hexagonal
      discs laid one above the other. The protein contains 108 haems per molecule and
      12 seryl, 12 threonyl, 35 glutamyl and 45 valyl residues to give a total number
      of 104 residues per molecule as N-terminal amino acids. These results lead us to
      a conclusion that the minimum molecular weight either per haem or per N-terminal
      residue is approximately 28,000 and the whole molecule consists of about 108
      subunits or peptide chains, each containing single haem. Further it is presumed
      that submultiple is a nonamer, composed of nine subunits.

PMID- 19768864
TI  - Replication of the single-stranded DNA of the male-specific bacteriophage M13.
      Isolation of intracellular forms of phage-specific DNA.
AB  - The intracellular DNA has been isolated from Escherichia coli F+ cells infected
      with the small male-specific bacteriophage M13 and fractionated on a methylated
      albumin-kieselguhr column. Two infectious forms of phage-specific DNA were
      isolated and identified as a double-stranded replicative form and single-stranded
      DNA on the basis of their elution from the methylated albumin-kieselguhr column,
      infectivity to spheroplasts before and after heating, sedimentation at low ionic
      strength and buoyant density in CsCl. The replicative DNA was found to be
      resistant to thermal denaturation, suggesting that it may be a closed ring. It is
      estimated that there are at least 130 molecules of replicative DNA and 190
      molecules of single-stranded DNA per infected bacterium.

PMID- 19768865
TI  - Replication of the single-stranded DNA of the male-specific bacteriophage M13:
      circular forms of the replicative DNA.
AB  - Equilibrium centrifugation in caesium chloride, band sedimentation in alkaline
      solutions and electron microscopy have been used to study purified preparations
      of the M13 replicative DNA. The buoyant density of the M13 replicative DNA in a
      CsCl density gradient is 1.701, compared to a density of 1-710 for Escherichia
      coli DNA. When the replicative DNA is sedimented in alkaline solutions of CsCl (p
      = 1.35), two components are observed with uncorrected s-values of 48.6 +/- 0.2
      and 15.2 +/- 0.5. Treatment of the replicative DNA with pancreatic DNase reduces
      the relative amount of the fast component in alkaline CsCl and similarly
      increases the relative amount of the slow component. Electron microscopic
      observation of the replicative DNA also shows two different forms of DNA,
      extended circles and condensed forms of DNA. The relative amount of condensed
      forms of DNA in a preparation of replicative DNA is equal to the relative amount
      of the fast component in alkaline velocity sedimentation. The average contour
      length of the extended circles is 2.19 +/- 0.07 micro.

PMID- 19768866
TI  - Uber infektiose Substrukturen aus Bakteriophagen. VI. A simple method for
      separating the replicative form from single-stranded phiX174 DNA.
AB  - A selective adsorption method is presented which allows a rapid separation of
      phiX174 replicative form DNA from single-stranded phiX174 phage DNA, facilitating
      the handling of a large number of samples. The single-stranded phiX174 DNA is
      selectively adsorbed to silicic acid coated with methylated albumin. After
      removal of the adsorbent by sedimentation, at least 40% of the input replicative
      form DNA is recovered in the supernatant fraction; the ratio of replicative form
      to single-stranded phage DNA is increased 20- to 200-fold. The potential of the
      method for separating other nucleic acids is discussed.

PMID- 19768867
TI  - Uber infektiose Substrukturen aus Escherichia coli Bakteriophagen. VIII. On the
      tertiary structure and biological properties of phiX174 replicative form.
AB  - As already known, phiX174 replicative-form DNA is separated into two components
      when sedimented in a sucrose gradient. The faster component, I, is not denatured
      by heat treatment, whereas the slower component, II, is converted to single
      strands. Only the infectivity of component II increases after heat denaturation.
      A quantitative comparison of data obtained by band centrifugation and by electron
      microscopy shows that the tertiary structure of component I is a highly twisted
      circle and that of component II an extended circle. By treatment with DNase,
      component I (as observed in band centrifugation) and twisted rings (as observed
      by electron microscopy) are converted at the same rate to component II and to
      extended circles and linear molecules. The plating efficiency of replicative-form
      DNA, in contrast to denatured component II replicative form and to phiX174 single
      stranded DNA, is diminished by the addition of Escherichia coli DNA to the
      adsorption medium. The inhibition by E. coli DNA at concentrations above 0.5
      microg/ml. is of first order. The lower the relative plating efficiency of native
      replicative-form DNA, the greater is the increase of infectivity for the
      denatured component II. The importance of these findings with respect to normal
      test conditions is discussed. Some observations suggest that under ideal test
      conditions the relative plating efficiency of the replicative-form DNA may rise
      to that of phiX174 single-stranded DNA.

PMID- 19768868
TI  - The appearance of circular DNA after lysogenic induction in Escherichia coli
      CR34(lambda).
AB  - A circular (non-ended) form of DNA is synthesized both after ultraviolet light
      and after thymineless induction of the lysogen Escherichia coli CR34(lambda).
      This new DNA species is shown to have characteristics identical to the circular
      DNA formed from lambda phage DNA immediatelyafter infection. Thus, the formation
      of a circular lambda DNA isnot limited to that derived directly from an infecting
      phage DNA but is also formed during the normal replication of the lambda DNA
      after lysogenic induction. The circular lambda DNA formed after lysogenic
      induction contains no detectable amounts of the bacterial genome. Once formed in
      the cell, the circular DNA species is stable and not significantly degraded.

PMID- 19768869
TI  - Methylation and processing of ribosomal RNA in HeLa cells.
AB  - The methylation of RNA in HeLa cells has been studied. After incorporation of
      radioactive methyl-labeled methionine, the cells were fractionated into
      cytoplasmic, nuclear, and nucleolar fractions. Methylation of high molecular
      weight RNA is shown to be exclusively in the 45 s ribosomal RNA precursor and
      takes place in the nucleolus. The methylation of the 45 s RNA apparently occurs
      close to the growing point of newly synthesized RNA as evidenced by the existence
      of methylated, partially completed molecules after very short pulse labeling. The
      methyl-labeled RNA was chased with non-radioactive methionine and the progression
      of the ribosomal RNA precursors was followed through the cell fractions. The data
      support the previously published hypothesis that nucleolar 45 s RNA is the
      precursor to cytoplasmic 18 s RNA and 32 s nucleolar RNA. The 32 s RNA is
      converted to 28 s RNA, which is then found in the nucleoplasm and is the apparent
      precursor to cytoplasmic 28 s RNA.

PMID- 19768870
TI  - The effect of chloramphenicol in intact erythroid cells.
AB  - Incubation of intact reticulocytes with chloramphenicol at concentrations over
      10(-3) M caused inhibition of protein synthesis and conversion of polyribosomes
      to single ribosomes. At 3 x 10(-3) M-chloramphenicol these effects were
      completely reversible, but reversibility decreased as the chloramphenicol
      concentration was raised above this level. 3 x 10(-3) M-chloramphenicol also
      caused a 15% decrease in the ATP content of reticulocytes. Evidence was obtained
      that the intracellular concentration of chloramphenicol in reticulocytes was
      approximately equal to the concentration in the incubation medium. L(+)threo
      chloramphenicol inhibited protein synthesis in reticulocytes, and chloramphenicol
      inhibited the synthesis of both hemoglobin and RNA in bone marrow cells. These
      results indicate that the action of chloramphenicol in these cells is different
      from that in bacteria.

PMID- 19768871
TI  - RNA codons and protein synthesis. Xi. Template activity of modified RNA codons.
AB  - Substituting 5'-, 2'-, 3'-terminal or 2'-internal ribose hydroxyls of
      oligonucleotides markedly affected their template activity in directing the
      binding of AA-sRNA to ribosomes. The relative template activity of oligo U
      preparations was as follows: p-5'-UpUpU > UpUpU > CH3O-p-5'-UpUpU > UpUpU-3'-p >
      UpUpU-3'-p-OCH3 > UpUpU-2',3'-cyclic phosphate. Trimers with (2'-5')
      phosphodiester linkages, (2'-5')-UpUpU and also (2'-5')-ApApA, did not serve as
      templates for phenylalanine- or lysine-sRNA, respectively. The relative template
      efficiency of oligo A preparations was as follows: p-5'-ApApA > ApApA > ApApA-3'
      p > ApApA-2'-p. The hexamer, ApApApApApA was considerably more active as a
      template than the corresponding pentamer. These data indicate that two adjacent
      triplets are recognized by two AA-sRNA molecules bound to nearby ribosomal sites.
      A doublet with 5'-terminal phosphate, pUpC, served as a template for serine-sRNA,
      whereas a doublet without terminal phosphate, UpC, did not. Although the template
      efficiency of pUpC was lower than that of the triplet UpCpU the data show that
      serine-sRNA can recognize pUpC.

PMID- 19768872
TI  - Acrylamide gel electrophoresis of radioactive ribosomal protein.

PMID- 19768874
TI  - The mission statement of every institution, hospital, and medical group declares
      the professional commitment to provide care that is " the most up-to-date" and
      "state-of-the-art".

PMID- 19768873
TI  - Relationship between the positioning of pyrrolidine residues and the stability of
      collagen.

PMID- 19768875
TI  - Review of the NCCN Clinical Practice Guidelines.

PMID- 19768876
TI  - Breast cancer Clinical Practice Guidelines in Oncology.
AB  - The therapeutic options for patients with noninvasive or invasive breast cancer
      are complex and varied. In many situations, the patient and physician have the
      responsibility to explore and select jointly the most appropriate option from
      among the available alternatives. With rare exceptions, the evaluation,
      treatment, and follow-up recommendations in these guidelines were based largely
      on the results of past and present clinical trials. However, there is not a
      single clinical situation in which the treatment of breast cancer has been
      optimized with respect to either maximizing cure or minimizing toxicity and
      disfigurement. Therefore, patient/physician participation in prospective clinical
      trials allows patients to not only receive state-of-the-art cancer treatment but
      also to contribute to improving the treatment of future patients.

PMID- 19768877
TI  - Decision-making for patients with resectable breast cancer: individualized
      decisions for and by patients and their physicians.
AB  - Decisions regarding the use of adjuvant cytotoxic and hormonal therapies for
      women with breast cancer ideally should be made jointly by the patient and
      oncologist. For patients to be adequately involved in this decision-making
      process, they must be provided with appropriate education regarding the potential
      benefits and risks of adjuvant therapies. The recommended steps for doing this
      are: 1) understand baseline prognosis with locoregional therapy (surgery,
      radiation, or both) alone for the individual patient at hand; 2) determine the
      estimated benefit afforded by adjuvant therapy options for the individual
      patient; 3) estimate the risk of side effects of adjuvant therapy options; 4)
      convey the above information to the individual patient; 5) facilitate the
      individual patient's decision regarding adjuvant systemic therapy; and 6) support
      the patient's decision. Two computer-based tools (Numeracy and Adjuvant!) are
      available to facilitate this process.

PMID- 19768878
TI  - Point: sentinel lymph node biopsy is indicated for patients with DCIS.
AB  - Sentinel lymph node (SLN) biopsy, a new standard of care for staging invasive
      breast cancer, remains controversial for ductal carcinoma in situ (DCIS).
      Although DCIS has a natural history in which long-term distant disease-free
      survival (DDFS) is 98% to 99% and axillary node metastases are historically rare,
      three recent DCIS series have found SLN metastases in a surprising 6% to 13% of
      patients. The strongest argument for SLN biopsy in DCIS is the diagnostic
      uncertainty and inherent sampling error of conventional pathologic techniques.
      Definitive surgery (excision or mastectomy) reveals invasive cancer in 10% to 21%
      of patients with a preoperative core needle or surgical biopsy diagnosis of DCIS,
      all of whom become conventional candidates for SLN biopsy. In the absence of
      proven invasion, most positive SLN in DCIS are micrometastases detected by
      hematoxylin and eosin- and immunohistochemical-stained serial sections. An
      increasing body of evidence suggests that these are prognostically significant,
      not artifactual. We propose that DCIS patients with positive SLN have occult
      invasive cancers, and that the same may have been true for the 1% to 2% of DCIS
      patients who go on to develop distant metastasis, either after an invasive local
      recurrence or as a first event. We further suggest that the diagnosis of DCIS
      encompasses two patient populations: 1) a majority (perhaps 90%) with true in
      situ disease (or prognostically insignificant invasion), negative SLNs, and an
      expected DDFS of 100%; and 2) a minority (perhaps 10%) with occult invasion,
      positive SLNs, and an expected DDFS of perhaps 90%. Pending the development of
      predictive models for preoperative identification of this SLN-positive minority
      of DCIS patients, SLN biopsy is indicated in any DCIS patient who may have an
      underlying invasive cancer, especially those who require mastectomy. In DCIS, SLN
      biopsy may ultimately prove to be a more sensitive screening test for occult
      invasion than examination of the breast itself.

PMID- 19768879
TI  - Counterpoint: sentinel lymph node biopsy is not indicated for ductal carcinoma in
      situ.
AB  - The purpose of axillary surgery in breast cancer is to provide prognostic
      information to guide the choice of adjuvant systemic therapy. Axillary surgery
      for ductal carcinoma in situ (DCIS) was abandoned in the 1980s because of the
      extremely low risk of lymph node metastases and high survival rates. Most women
      with metastases probably harbored an unrecognized focus of invasion or had
      metastases subsequent to an invasive local recurrence. Increased use of the less
      morbid sentinel node biopsy (SNB) for axillary staging of invasive cancer and the
      recognition that many patients will harbor micrometastases in nodes only
      recognized by cytokeratin immunohistochemistry (IHC) led two groups to perform
      SNB with IHC in women with DCIS. One group included all subtypes of DCIS and
      found metastases in 13% (half of which were detected only on IHC). The other
      group studied only patients with "high-risk" DCIS. They found metastases in 12%
      (7 of 9 by IHC only). These groups recommend SNB for women with DCIS. However,
      the use of SNB in DCIS should be tempered by the uncertainty of the prognostic
      significance of IHC-detected metastases, the conflicting results of these 2
      studies, and the real potential to cause more harm than good from the morbidity
      of the procedure, the application of unnecessary axillary dissection, and the use
      of unwarranted adjuvant systemic chemotherapy. These results should be used to
      generate hypotheses for clinical trials addressing these problems. However, SNB
      for DCIS remains investigational and should not be generally applied.

PMID- 19768880
TI  - The aromatase inhibitors as adjuvant therapy for hormone receptor-positive breast
      cancer.
AB  - Adjuvant hormonal therapy has been shown to decrease the risk of breast cancer
      recurrence and overall mortality in patients with hormone receptor-positive
      breast cancer. Tamoxifen has been used in this setting for many years, both in
      premenopausal and postmenopausal patients. Tamoxifen is not devoid of toxicity,
      and attempts have been made to develop newer hormonal agents with better efficacy
      and less toxicity. The aromatase inhibitors have shown equivalent or superior
      efficacy to tamoxifen in the treatment of metastatic breast cancer, and efforts
      are underway to determine the role of these agents in early breast cancer. The
      ATAC trial recently showed that use of the third-generation aromatase inhibitor
      anastrozole in the adjuvant setting led to a modest improvement in relapse-free
      survival as compared with tamoxifen. Patients treated with anastrozole were also
      less likely to develop uterine cancer or experience a thromboembolic event.
      However, patients treated with anastrozole were more likely than those treated
      with tamoxifen to suffer a fracture or other musculosketal problem. An ASCO
      technology assessment panel reviewed the relevant data and issued a consensus
      statement regarding the use of aromatase inhibitors in the adjuvant setting. In
      general, the panel favored the continued use of tamoxifen as adjuvant hormonal
      therapy for most postmenopausal women. Within the next few years, further data
      from the ATAC trial and from other trials of aromatase inhibitors in the adjuvant
      setting should be available to guide treatment recommendations for this patient
      population.

PMID- 19768881
TI  - Taxanes in the adjuvant treatment of breast cancer.
AB  - Adjuvant chemotherapy clearly demonstrates a reduction in mortality in breast
      cancer. However, the added benefit from the addition of taxanes remains
      uncertain. Paclitaxel and its cousin docetaxel have proven activity in the
      treatment of metastatic breast cancer. Toxicity has been tolerable when taxanes
      are used as single agents or in combination with anthracyclines. Several clinical
      trials are currently underway evaluating the role of taxanes in the adjuvant
      setting. Preliminary results from large phase III studies are promising; however,
      mature data are required before conclusions can be drawn. This article reviews
      the trials currently underway, evaluating the efficacy, dosage, scheduling, and
      regimens of taxanes in the adjuvant treatment of breast cancer.

PMID- 19768882
TI  - The role of bisphosphonates in breast cancer.
AB  - Breast cancer frequently metastasizes to bone. Metastases result in skeletal
      morbidity including pathologic fractures, the need for radiation or surgery to
      bone, spinal cord compression and hypercalcemia. The pathophysiology of bone
      destruction is related to activation of osteoclasts by tumor-derived and bone
      marrow microenvironmental factors. One prominent osteoclast-activating factor
      associated with breast cancer is parathyroid hormone-related peptide (PTHrP).
      Bisphosphonates have been shown to impair osteoclast activity by decreasing
      recruitment from the monocyte macrophage cell line, inhibiting osteoclast
      function at the bone site and causing osteoclasts to undergo apoptosis. Clinical
      studies with bisphosphonates show an improvement in the control of hypercalcemia
      and a reduction in skeletal related morbidity with administration of pamidronate
      and zoledronic acid. Bisphosphonates have become the standard of care for
      osteolytic metastases associated with breast cancer. Recent data with zoledronic
      acid found that skeletal related morbidity may be reduced regardless of the
      radiographic picture of skeletal metastases. Thus, zoledronic acid may be
      valuable in osteolytic and osteoblastic disease as well as in disease with an
      osteolytic or osteoblastic radiographic appearance. In breast cancer with
      osteolytic disease, zoledronic acid may be more effective than pamidronate in
      reducing skeletal morbidity and prolonging the time to first skeletal event.

PMID- 19768883
TI  - Breast Cancer Screening and Diagnosis Clinical Practice Guidelines in Oncology.
AB  - The intent of these guidelines is to give health care providers a practical,
      consistent framework for screening and evaluating a spectrum of breast lesions.
      Clinical judgment should always be an important component of optimal management.
      If the physical breast examination, radiologic imaging, and pathologic findings
      are not concordant, the clinician should carefully reconsider the assessment of
      the patient's problem. Incorporating the patient into the health care team's
      decision-making empowers the patient to determine the level of breast cancer risk
      that is personally acceptable in the screening or follow-up recommendations.

PMID- 19768884
TI  - An overview of mammography: benefits and limitations.
AB  - Although broad consensus exists that mammography is beneficial, there has been
      persistent and evolving debate over the extent of the benefit, as well as
      concerns about cost-effectiveness. Ongoing evaluation of the world's randomized
      clinical trials as well as new evaluations of population service screening (ie,
      organized, community-based screening) clearly show that mammography is beneficial
      and that the benefit of modern mammography among women who attend screening
      exceeds what has conventionally been estimated from the trials. Limitations of
      mammography include human and financial costs associated with missed cancers and
      false-positive results. However, it is important to distinguish those limitations
      of mammography that are inherent limitations of the technology from those that
      can be reduced through greater attention to quality assurance.

PMID- 19768885
TI  - New technologies in breast imaging.
AB  - Large, randomized controlled trials have proven the efficacy of mammography in
      reducing breast cancer mortality. However, the known deficiencies of mammography
      have led to the development of new technologies. Magnetic resonance imaging
      (MRI), digital mammography, computer-assisted diagnosis, positron-emission
      tomography (PET), technetium 99m sestamibi, and expanding roles for breast
      ultrasound have been explored as tools in breast cancer detection and evaluation.
      This article discusses these modalities and their current uses.

PMID- 19768886
TI  - Breast Cancer Risk Reduction Clinical Practice Guidelines in Oncology.
AB  - Breast cancer risk factor analysis allows the identification of women at very
      high risk for the future development of breast cancer. Many of the known risk
      factors are either not modifiable or are not reasonably modifiable because of
      social implications or other potential health benefits (eg, those associated with
      hormone replacement therapy). Thus, effective strategies to decrease the risk of
      breast cancer are needed. The recent demonstration that the use of tamoxifen for
      5 years decreases the future risk of breast cancer by approximately 49% provides
      the opportunity for a risk-reduction intervention. Women taking tamoxifen must be
      monitored for the occurrence of well-defined toxicities, including hot flashes
      and, more rarely, endometrial carcinoma, thromboembolic disease, and cataract
      formation. Strategies are available for the management of tamoxifen toxicity. In
      special circumstances, such as in carriers of BRCA1 or BRCA2 mutations, the risk
      of future breast cancer is very high, and the performance of a bilateral
      prophylactic mastectomy may be considered. Women considering bilateral
      prophylactic mastectomy should undergo multidisciplinary consultation so that
      they may make a fully informed decision. The panel strongly encourages patients
      and health care providers to participate in clinical trials to test new
      strategies for decreasing the risk of breast cancer. Only through the accumulated
      experience gained from well-designed, prospective clinical trials will additional
      advances in the reduction of breast cancer risk be realized.

PMID- 19768887
TI  - Breast cancer risk assessment: a guide for clinicians using the NCCN Breast
      Cancer Risk Reduction Guidelines.
AB  - Breast cancer, a complex and heterogeneous disease, is the most common malignancy
      diagnosed in women in the United States, with over 180,000 new cases and
      approximately 44,000 deaths per year. Breast cancer risk is influenced by a large
      number of factors, including age, family history, reproductive and hormonal
      history, proliferative breast conditions, physical activity, diet, and
      environmental exposures. These factors all interact in a complex manner to
      contribute to the risk of developing breast cancer. Because the interactions
      between risk factors are poorly understood at the molecular level, it is
      difficult to accurately evaluate the breast cancer risk of a given person
      presenting with an individual constellation of factors. To better define the
      population at increased risk that may warrant specific intervention, several
      models exist to estimate a woman's risk for developing breast cancer and for
      harboring a germline mutation in a cancer susceptibility gene. This article
      summarizes these models and gives brief guidelines about which model may be
      preferable given a specific family history.

PMID- 19768888
TI  - Treatment needs of women arrested for domestic violence: a comparison with male
      offenders.
AB  - Rising numbers of women arrested for domestic violence present many theoretical
      and practical challenges. At the theoretical level, there is ongoing debate about
      whether women are equally aggressive as men. At the practical level, little
      research is available to guide how female cases are handled in the criminal
      justice system. In this study, data were obtained regarding demographic
      characteristics, mental health functioning, and childhood familial dysfunction
      for a large sample of male (n = 2,254) and female (n = 281) domestic violence
      offenders. The women were demographically similar to the men, and few differences
      were noted in their childhood experiences. Women were more likely than men to
      have previously attempted suicide, whereas more men had conduct problems in
      childhood and substance abuse in adulthood. Compared to the male offenders, women
      reported more symptoms of personality dysfunction and mood disorder. Treatment
      implications of these findings are discussed.

PMID- 19768889
TI  - Prevalence and characteristics of psychological abuse reported by court-involved
      battered women.
AB  - This study describes the prevalence and correlates of psychological abuse in a
      sample of 3,370 adult women assaulted by male intimate partners. Victims were
      asked about their history of physical and psychological abuse, characteristics of
      the current offense, perpetrator characteristics, and their own response to the
      abuse. Prior psychological abuse was reported by most (80%) of the women, and
      rarely did physical aggression occur in the absence of psychological abuse. Men
      with a history of extrafamilial criminality and substance abuse were more likely
      to engage in psychological abuse, while demographic characteristics of the
      offenders showed little relationship to the use of these emotionally abusive
      tactics. Additional analyses suggested that psychological abuse, independent of
      physical aggression, was related to victims' perceived threat and plans to leave
      the relationship. These findings indicate the need for evaluation of
      psychological abuse, independent of physical abuse, to understand its impact on
      victims.

PMID- 19768890
TI  - Screening for intimate partner violence when children are present: the victim's
      perspective.
AB  - Although intimate partner violence (IPV) is routinely encountered in health care,
      it often goes undetected. Medical organizations recommend routine screening of
      women alone without children of partner. Separating a mother from her children
      may not be feasible in busy practices. Therefore, screening may not occur. Little
      research has examined women's desires about IPV screening in front of their
      children. This study interviewed 32 mothers/survivors who were in either an
      IPVshelter or support group regarding their wishes about IPV screening and
      discussions in front of their children. Interviews were audio taped, transcribed,
      and analyzed using thematic analysis techniques. Major themes included
      mothers'comfort with the use of general IPV screening questions in front of
      children ages 3 to 12 years. In summary, most mothers/survivors were comfortable
      with physicians using general questions to screen for IPV but preferred in-depth
      discussions about the abuse and resource sharing in private.

PMID- 19768891
TI  - Predicting violent behavior through a static-stable variable lens.
AB  - This study examines the differential relationship of criminogenic domains to
      violent and nonviolent recidivism in a sample of predominantly violent offenders.
      In addition, the criminogenic domains are examined through a static-stable
      variable dichotomy. The results support previously published retrospective
      studies that found different domains associated with violent and nonviolent
      offending. In addition, the results showed that stable variables add to the
      prediction of both violent and nonviolent behavior after accounting for the most
      salient static variables. The results are discussed within the context of
      improving risk prediction.

PMID- 19768892
TI  - Cognitive distortions of religious professionals who sexually abuse children.
AB  - This study uses grounded theory to investigate the cognitive distortions in the
      self-report statements of 14 clergymen who had sexually abused children. These
      clergy were residents at an assessment and treatment center for child molesters.
      The content of the offenders'cognitive distortions was identified and categorized
      into thematic groups. These categories were found to relate to the various stages
      of the offending cycle. A tentative model was generated that illustrates the
      relationship between the categories and the hypothesized sequence of thought
      facilitating the initiation and maintenance of sexually abusive behavior In
      addition, a number of cognitive processes were identified as contributing to
      offenders' beliefs. The study also reveals that the clergymen used their
      religious role and relationship with God within their distorted beliefs. These
      beliefs were predominantly concentrated in the areas of giving themselves
      permission to offend, denial of likelihood of getting caught, reduction of guilt
      after offending, and maintaining a positive sense of self.

PMID- 19768894
TI  - Cyclical changes of homicide rates: a reanalysis of Brearley's 1932 data.
AB  - The objective of this analysis is to explore the possibility that Brearley's
      failure to detect a coherent pattern of seasonal variation in his well-known
      study of homicide in the United States was due to a lack of statistical
      refinement. The original data on homicides in the United States between 1923 and
      1928 (N = 51,798) were reanalyzed using spectral analysis. The results show a
      significant seasonal dependency with a peak in the homicide rate in August. The
      seasonal dependency explains between 23% and 30% of the total homicide variance.
      The importance of this finding is the degree of explained variance and the
      location of the peak, which is remarkably consistent with more contemporary
      studies using similar methods despite substantial sociodemographic changes,
      suggesting an endogenous etiology.

PMID- 19768893
TI  - Childhood and adult abuse among women in primary health care: effects on mental
      health.
AB  - The study looked at 557 women participating in an evaluation of a domestic
      violence screening intervention in a primary care setting. Depression and anxiety
      were investigated in relation to seven types of child and adult intimate partner
      abuse. At the bivariate level, both physical and sexual child abuse were
      associated with significantly increased risk for all five types of adult abuse as
      well as depression and anxiety. Multivariate analyses suggested that recent
      intimate partner violence and high-severity child abuse increased risk for
      depression, and both recent and past intimate partner violence as well as child
      abuse increased risk for anxiety. In addition, higher levels of cumulative abuse
      increased risk for depression and anxiety over the life span even after
      controlling for other risk factors.

PMID- 19768895
TI  - [Overview of functional somatic syndromes].

PMID- 19768896
TI  - [Concept of functional somatic syndromes].
AB  - "Functional somatic syndromes" is one of the new terminologies in the medicine.
      However most of the primary-care physicians have already noticed the existence of
      the patient appeal their physical symptoms which is medically unexplained for a
      long time. On the other hand, the psychiatrists looked same physical symptoms as
      a symbolic representation of the patients' psychological conflicts, somatoform
      disorders. This new terminology "functional somatic syndromes" intends to
      integrate those two dimensions and to understand the patient as a whole person.
      In this special issue, we show the multi-dimensional aspects of "functional
      somatic syndromes" and intend to serve the clue to understand the patients with
      symptoms to all primary-care physicians in Japan.

PMID- 19768897
TI  - [Psychosomatic disorder and functional somatic syndrome].
AB  - Functional somatic syndrome (FSS) has received a great deal of attention in
      recent years, and most have been treated as psychosomatic disorders. A
      psychosomatic disorder is a physical disorder that is closely related to
      psychosocial factors that affect the onset or clinical course of the disease. For
      most patients with FSS, the mind-body relationship is related to psychosocial
      stress. It is important to consider the psychosocial background of the patient as
      it relates to their pathology. Our psychosocial model that includes four
      psychosocial factors and our five-step treatment program for patients with
      functional somatic syndromes are presented.

PMID- 19768898
TI  - [Etiology of functional somatic syndromes].
AB  - Functional somatic syndromes are defined as several related syndromes that are
      characterized more by symptoms, suffering, and disability than by structural or
      functional abnormality. These syndromes include irritable bowel syndrome, tension
      type headache, chronic fatigue syndrome, and fibromyalgia. Such syndromes have
      similarities in terms of definition, diagnosis, etiology, and treatment. To
      elucidate the pathogenesis of functional somatic syndromes, it is important to
      focus on gender-related factors, comorbidities of depression and anxiety,
      physiological responses like autonomic nervous function and hypothalamic
      pituitary-adrenal axis, and patient-doctor relationship. Based on recent
      literatures, mood state and somatosensory amplification are suggested to play an
      important role in the psychopathological mechanism of functional somatic
      syndromes, and genetic and environmental factors need to be considered as well.

PMID- 19768899
TI  - [Pathology of functional somatic syndrome].
AB  - The core pathological concept of functional somatic syndrome (FSS) is the
      discrepancy between patients' subjective experience of somatic symptoms and
      objective explanation by medical evaluation. Based on the discrepancy, the
      somatic symptoms with medically unexplained origins maintains, prolonged
      chronically, and grow up to FSS owing to various factors; physiological pathways,
      mood disturbance such as anxiety or depression, doctor-patient relationship,
      psychosocial stresses, alexithymia and alexisomia, and lack of support systems.
      As the pathology becomes more and more complicated, the psychosocial stresses,
      mood disturbance, and physiological dysfunction become more significant. Thus,
      the pathology falls into a vicious circle. Patients with FSS have common problems
      or characteristics, and have several overlapped diagnoses. FSS should be treated
      from aspects of both the similarity and the difference.

PMID- 19768900
TI  - [Somatization and FSS].
AB  - In this paper, we discussed the relationship between somatization and functional
      somatic syndrome (FSS). The concept of somatization takes its origin from the
      work of Freud S who proposed the idea of conversion as a main defense mechanism.
      At the same period, the term somatization was introduced by Stekel W as a
      hypothetical process whereby a deep-seated conflict could cause a bodily
      disorder. After that, Alexander F developed the emotional equivalents, which had
      been also proposed by Freud S, into the concept of the vegetative neurosis and
      psychosomatic diseases. Recently, somatization tends to be defined as 'a tendency
      to experience and communicate somatic distress in response to psychosocial stress
      and to seek medical help for it' (Lipowski ZJ, 1988). So there seems to be a
      strong link among conversion, somatization, FSS, and somatization disorder.

PMID- 19768901
TI  - [Functional somatic syndromes from the view of cultural anthropology].
AB  - The functional somatic syndromes have acquired major socio-cultural and political
      dimensions. Socio-cultural factors clearly affect symptoms, suffering, and
      disability perception and reporting. And knowledge of explanatory models of
      bodily distress for patients from different cultural backgrounds is useful in the
      establishment of a stable doctor -patient relationship. FSS may be an operational
      category to bridge between medical explanatory model and patient's model.
      According to medical anthropology, sickness has two faces; illness and disease.
      "Disease" is the problem from the practitioner's perspective, and "illness" is
      the human experience of symptoms and suffering. In this paper, the
      anthropological research on chronic fatigue syndrome as "not real" illness
      experience was described.

PMID- 19768902
TI  - [Functional somatic syndrome: from the viewpoint of narrative-based medicine].
AB  - The concept of functional somatic syndrome (FSS) may be useful to categorize the
      patients with indefinite multiple complaints without organic disease, and to
      manage them well. From the perspective of narrative approach in medicine, a
      narrative is a chronological account of the patient's experience of suffering,
      which starts in his/her life-world and is socially constructed and re-constructed
      through the transaction with health-professionals as well as ray-people. Through
      narratives, the patient can make sense on his/her illness experience. Sharing a
      good illness narrative may transform both the sufferer and the experience of
      suffering and may be salutogeneic. In this paper, the concept of FSS is discussed
      from the perspective of narrative construction of illness, and is examined
      whether it is more useful than other traditional disease concepts.

PMID- 19768904
TI  - [Functional somatic syndrome from the viewpoint of comprehensive medicine].
AB  - Comprehensive medicine represents a medical treatment which is provided based on
      comprehensive understanding of patients, by grasping each patient as "a person
      who is living, now and here" in any case at any time. Its basic model was created
      by Day SB, Frankl VE and others as the biopsychosocial-existential model. In
      practicing this medicine, Ikemi Y and Nagata K introduced Oriental medicine into
      the modern medicine (Occidental medicine), and they proposed that establishment
      of psychosomatic medicine as the interface between the two should be essential.
      This concept has become the base of the integrative medicine, and its objective
      is to provide comprehensive medicine. Functional somatic syndrome (FSS) cannot be
      comprehended by the pathogenetic modern medicine. FSS can first be grasped in the
      concept of salutogenesis. In Oriental medicine, a functional pathological
      condition is regarded as an unorganized disease, and doctors who treat such
      patients are called "Jyo-i" (superior doctors). Therefore, there are many methods
      to assess the functional pathological conditions in the concept of Oriental
      medicine. On the other hand, doctors who are accustomed to establish diagnosis or
      treat organic diseases may misdiagnose FSS as a psychological disease
      (somatogenic pseudoneurosis) in not a few cases. FSS is affected by the lifestyle
      specific to individual patients. Therefore, it is essential to understand these
      patients comprehensively, namely biologically psychological, socially and
      existentially.

PMID- 19768903
TI  - [FSS and SAS].
AB  - Patients with obstructive sleep apnea syndrome (OSAS) have a morphological and
      functional abnormality of the upper respiratory tract, and the obesity of these
      patients is the main cause for OSAS. Obese patients with OSAS are closely
      associated with life-style related diseases and metabolic syndromes. The
      circulatory system is most strongly influenced by OSAS and hypertension,
      cerebrovascular disease and cardiovascular disease are the prime complications of
      OSAS. A psychosomatic approach is required for the treatment of OSAS in patients
      with obesity. The pathophysiology of upper airway resistance syndrome (UARS) is
      similar to OSAS in that there is abnormal airway resistance in the upper airway
      during sleep, but UARS does not meet the diagnostic criteria of OSAS. UARS should
      be classified as a separate syndrome or as part of the larger group of sleep
      disordered breathing (SDB). Patients with UARS have a clinical condition that
      differs from that of patients with OSAS and resembles the condition of patients
      with functional somatic syndrome (FSS). We sometimes find slightly lower levels
      of night arterial saturation in patient with unidentified somatic symptoms. This
      is also found in patients with UARS. It is necessary to examine the respiratory
      events of patients with FSS and unidentified somatic symptoms during sleep.

PMID- 19768905
TI  - [Family medicine and functional somatic syndromes].
AB  - Between psychosomatic medicine and psychiatry, FSS (functional somatic syndromes)
      patients are often visiting a family doctor. For FSS, the role of family
      physicians is large, but the family physicians are not required for the role of
      diagnosis and treatment of FSS. Rather, appropriate referral to a specialist to
      exclude organic disease is important and a role as the coordinator is large to
      the patient to refuse a psychiatric consultation. To serve as a role for such
      coordination, a family physician has to response the patient's emotional side and
      focus on the construction of the doctor-patient relationship and response. I also
      think of structuralism medicine approach to describe disease from the meta-level
      as a new procedure to the patient. This approach consists of 4 components,
      'entity', 'phenomenon', 'words', and 'I'. This may be a useful approach to family
      physicians who coordinate the overall for FSS patients' management.

PMID- 19768906
TI  - [Functional somatic syndrome in general practice].
AB  - General practitioners (GPs) see many patients with various symptoms such as
      dizziness, general fatigue, chronic headache, numbness, chronic upper abdominal
      pain and chronic diarrhea and these patients often have no abnormal findings in
      diagnostic tests. Even some specific conditions are categorized as "diseases"
      such as "fibromyalgia" and "non-ulcer dyspepsia", the patients actually suffer
      from various illnesses and have common questions. One is "Why am I suffering from
      such illness?" and the other is "How can I waive from the suffering?". GPs should
      usually face with these patients' questions. Even without categorization by
      "functional somatic syndrome", GPs provide continuity of care and sometimes
      provide prescriptions for such patients. The concept of postmodern is essential
      in management of functional somatic syndrome.

PMID- 19768907
TI  - [Features and clinical management of functional somatic syndromes in gynecology].
AB  - Premenstrual syndrome (and premenstrual dysphoric disorder: PMDD) and chronic
      pelvic pain (CPP) are considered functional somatic syndromes (FSS) in
      gynecological practical medicine. Some of them often cannot keep life in society.
      Painkillers are effective in quite few patient. Therefore psychotherapy is
      considered essential for the therapy. On certain occasions, complementary and
      alternative medicine achieve a lasting improvement of pain. At the present time,
      standard clinical management as well as pathology are not yet established. The
      practice of integral, whole person, narrative based, and gender specific medicine
      may be recommended.

PMID- 19768908
TI  - [Is "functional somatic syndrome" clinically useful?].
AB  - The functional somatic syndrome is applied to several syndromes characterized by
      medically unexplained physical symptoms, such as irritable bowel syndrome,
      fibromyalgia, chronic fatigue syndrome, etc. Both physical and psychiatric
      treatments are usually necessary for these syndromes and the term functional
      somatic syndrome was advocated to inform clinicians in America of this fact.
      However, We believe this term will not be useful in Japan, because most Japanese
      clinicians are already aware of this fact and treatment is different in each
      syndrome included in FSS.

PMID- 19768909
TI  - [Gastroenterology and FSS].
AB  - Functional gastrointestinal disorders (FGIDs) such as functional dyspepsia (FD)
      and irritable bowel syndrome (IBS) are included in functional somatic syndromes
      (FSS), which are designated as medically unexplained physical symptoms.
      Pathopysiology of these diseases are characterized by multi-functional disorders
      of the gastrointestinal (GI) tract including psychosomatic sensation, brain-gut
      interaction, autonomic nervous systems, motility disorders, local inflammation,
      and visceral perception. However, the standard therapy for these diseases is not
      established, since predominant factors among them associated with respective
      patients are difficult to be identified in a clinical field. In this section, we
      are going to present the accumulating evidences for the pathophysiology and
      therapeutic strategy of FD and IBS.

PMID- 19768910
TI  - [Pain and FSS in rheumatology clinic].
AB  - Physical condition with chronic widespread pain accompanied by characteristic
      tenderness has been categolized in part as "fibromyalgia" according to the
      American College of Rheumatology 1990 classification criteria. However, the
      criteria still evokes argument in regard to its validity, and in particular, to
      the count of tender points. The symptoms of musculoskeletal pain and tenderness
      are often found also in healthy population, and pain may be shown as a dominant
      complaint in depression or somatic pain disorder in psychiatric field. The long
      standing widespread pain, therefore, would be rather recognized as one of
      conditions in a spectrum of functional somatic syndrome (FSS), and this
      intractable disorder should be treated under the broad concept of FSS in a
      multidisciplinary fashion.

PMID- 19768911
TI  - [Functional somatic syndrome in dental practice].
AB  - Functional somatic syndromes (FSSs) are common in dental as well as medical
      practice. Many patients with unexplained symptoms in oro-maxillo-facial areas
      visit dentists, but they are not diagnosed and treated properly.
      Temporomandibular disorder, atypical facial pain, and glossodynia (burning mouth
      syndrome) are included in dental FSSs. These diseases overlap with each other and
      with FSSs in other organs, such as myofacial pain syndrome, tension-type
      headache, fibromyalgia, and chronic fatigue syndrome. They coexist with mental
      disorders, such as anxiety disorder, mood disorder, and somatoform disorder.
      Multidisciplinary and holistic approaches should be applied to dental FSSs;
      pharmacological therapy (antidepressants), physical therapy, and cognitive
      behavioral therapy. Clinicians have to support a patient in"enjoying his/her life
      with symptoms". Dental specialists in "oral medicine" with psychosomatic
      viewpoints are now required.

PMID- 19768912
TI  - [Functional somatic syndromes in the treatment of allergic diseases and their
      related disorders].
AB  - Functional somatic syndromes (FSS) are characterized by patterns of persistent
      bodily complaints for which adequate examination does not reveal sufficiently
      explanatory structural or other specified pathology. Here we reviewed the
      following diseases or pathologies: nervous cough, vocal cord dysfunction,
      multiple chemical sensitivity and sick building syndrome. All of these often
      accompany co-morbid psychiatric disorders, such as anxiety disorder and
      depression. Therefore, bio-psycho-social understanding and approach are required
      for diagnosis and treatment of patients with these diseases. Specific
      psychotherapy may be applicable when symptoms are aggravated by psychological
      factors.

PMID- 19768913
TI  - [Treatment of myalgia].
AB  - Fibromyalgia (FM) conceptualized by the American College of Rheumatology is
      characterized by long-lasting chronic widespread pain and stiffness of the fibro
      muscular system associated with various unidentified symptoms. Since most of the
      patients are female and the onset and clinical course of FM involves various
      kinds of bio-psychosocial stress factors, it is very important to consider the
      psychosomatic background of the patient. The symptom of FM is not readily
      improved with conventional analgesic drugs, antirheumatic agents or various kinds
      of physiotherapy, however current guidelines recommend tricyclic antidepressants,
      SSRIs and SNRIs as first-line therapies to treat the multiple symptom of the FM.
      It is considered that antidepressants may operate the functional impairment of
      descending (efferent) analgesic system, in which serotonin and noradrenaline take
      an important role. Among 199 certified physicians of the Japanese Society of
      Psychosomatic Medicine, the largest number of respondents selected SSRI, SNRI and
      other antidepressants as first-line drugs. Because the psychological and physical
      exhaustion due to an irregular life style, physical strain, and accumulated
      fatigue may be the key stress factors for the organization of symptoms,
      psychosomatic approach and guidance should be conducted to enable patients to
      reduce stress in daily life. For the problems of personality and psychological
      stress, counseling and advanced psychotherapy such as cognitive behavioral
      therapy (CBT) should be also conducted.

PMID- 19768914
TI  - [Psychosomatic therapies in primary headaches].
AB  - Many previous studies have reported that primary headaches such as tension-type
      headache and migraine are influenced by psychosocial factors including stressful
      life events and daily hassles. In addition, noncompliance and nonadherence with
      medical regimens represent a major challenge to the treatment of primary
      headaches including medication-overuse headache. Therefore, non-pharmacological
      therapies such as relaxation, cognitive-behavioral therapy, and biofeedback have
      become important and their efficacy has been reported. In the present review, I
      would like to introduce the importance of psychosocial factors in primary
      headaches and psychosomatic therapies by reviewing previous studies on the
      association between psychosocial factors and primary headaches and on the
      efficacy of non-pharmacological therapies and by showing a representative case.

PMID- 19768915
TI  - [Treatment of functional somatic syndrome with abdominal pain].
AB  - Functional somatic syndrome (FSS) with abdominal pain include functional
      gastrointestinal disorder, chronic pancreatitis, chronic pelvic pain syndrome,
      which generally contain autonomic dysfunction. Regarding the treatment of FSS, it
      is important to know about FSS for a therapist at first. Secondly, the therapist
      should find out physical dysfunction of patients positively, and confirm
      objectively the hypotheses about both peripheral and central pathophysiological
      mechanisms as much as possible. Heart rate variability is an easy method, and
      useful to assess autonomic function. After grasping the patient's explanatory
      model about the illness, the therapist showes the most acceptable treatment for
      the patient at last.

PMID- 19768916
TI  - [Biomedical and psychosocial treatment of fatigue in functional somatic
      syndrome].
AB  - Fatigue is one of the most common complaints of patients with functional somatic
      syndrome (FSS), which includes chronic fatigue syndrome (CFS). Although the
      etiology of fatigue related to FSS remains unclear, accumulating evidence has
      shown that cognitive behavioral therapy and graded exercise therapy are effective
      for treating fatigue in patients with CFS. This suggests that psychosocial
      intervention and physical rehabilitation, as well as biomedical treatment, play
      an important role in treating fatigue in FSS patients. Here we provide an
      overview of the biomedical and psychosocial treatments for fatigue in cases of
      FSS.

PMID- 19768917
TI  - [Treatment of low back pain (pain of locomotive organs)].
AB  - Several diseases, including the functional somatic syndromes (FSS), are
      characterized by pain involving locomotive structures. These disorders include
      low back pain, neck-shoulder-arm syndrome and fibromyalgia. FSS patients are
      convinced that their illness is not a psychosomatic disorder, being instead a
      bodily disease. Therefore, physicians such as orthopedic surgeons play an
      important role in supporting patients suffering from FSS with locomotive pain,
      because these patients expect their physicians to treat them for a physical,
      rather than a psychological disorder. The author investigated the patient-doctor
      relationship in the examination room of a hospital, and designated pain combined
      with a depressive state characterized by agitation and helplessness, a common
      complaint made by FSS and psychosomatic disorder patients, 'painful depression'.
      Pain and depression influence each other and trigger a vicious downward spiral
      termed the 'pain-depression deflation spiral'. Generally, orthopedic surgeons can
      achieve good relationships with FSS patients with locomotive structure pain,
      despite suspicion of psycho-social factors. It is concluded that physical
      examinations and treatments by orthopedic surgeons, conducting physical
      examinations only, can serve as a very good psychosomatic approach to painful
      depression/FSS patients.

PMID- 19768918
TI  - [Treatment of dizziness as a symptom of functional somatic syndromes].
AB  - The term functional somatic syndrome (FSS) refers to several related syndromes
      characterized chiefly by symptoms, suffering, and disability and the absence of
      disease-specific, demonstrable structural or functional abnormalities. Dizziness
      is a common symptom of FSS. Generally, clinical examination in these cases is
      inconclusive. The complaints of these patients usually persist until a
      satisfactory treatment is administered. For the treatment of cases with FSS,
      first, signs of underlying psychological distress should be identified during
      history taking. It is essential to address the psychosocial aspect in these cases
      from a medical point of view. Drug therapy with serotonin reuptake inhibitors is
      therefore prescribed. Next, psychotherapy should be introduced. The final
      strategy usually is to collaborate with a clinical psychologist or psychiatrist.

PMID- 19768919
TI  - [Psychosomatic medicine for non-cardiac chest pain].
AB  - Recently, it has become problematic that the number of noncardiac chest pain
      (NCCP) patients are increasing among those who come to the emergency room with
      chest pain as a chief complaint. They tend to come to hospitals often and over
      many years, even after cardiac-chest pain has been excluded from their diagnosis.
      Moreover, studies have shown that NCCP patients have a high prevalence of
      anxiety, depression and disability. However, most NCCP patients are usually
      treated by cardiologists or primary physicians. Ordinary biomedical approaches
      often fail to treat NCCP. NCCP is one of the most important functional somatic
      syndromes from the view of medical economics. The cause of NCCP includes
      gastroesophageal reflux disease, panic disorder and esophageal dysmotility. In
      this review article, we summarize the definition, epidemiology, pathology, and
      process of diagnosis of NCCP. Finally, we propose a pathological hypothesis from
      a psychosomatic view. We discuss the effects of anxiety, fear and hyperactive
      behavior induced by affective stressors on the dysmotility and the lowering of
      the pain threshold.

PMID- 19768920
TI  - [Therapy for atypical facial pain].
AB  - Atypical facial pain is a pain in the head, neck and the face, without organic
      causes. It is treated at departments of physical medicine, such as dental, oral
      and maxillofacial surgery, otolaryngology, cerebral surgery, or head and neck
      surgery. In primary care, it is considered to be a medically unexplained symptom
      (MUS), or a somatoform disorder, such as somatization caused by a functional
      somatic syndrome (FSS) by psychiatrists. Usually, patients consult departments of
      physical medicine complaining of physical pain. Therefore physicians in these
      departments should examine the patients from the holistic perspective, and
      identify organic diseases. As atypical facial pain becomes chronic, other
      complications, including psychiatric complaints other than physical pain, such as
      depression may develop. Moreover, physical, psychological, and social factors
      affect the symptoms by interacting with one another. Therefore, in examining
      atypical facial pain, doctors specializing in dental, oral and maxillofacial
      medicine are required to provide psychosomatic treatment that is based on
      integrated knowledge.

PMID- 19768921
TI  - [Progress in antiarrhythmic therapy].
AB  - The number of patients with cardiac arrhythmias is increasing in our society with
      the aged people along with hypertension, diabetes mellitus, metabolic syndrome
      and ischemic heart diseases. Patient characteristics and therapeutic tools are
      both diverse at present, and, therefore, clinical evidence is one of the
      important pieces for selecting therapy suitable for our individual patients. This
      article reviews recent clinical trials regarding to atrial fibrillation and
      ventricular tachycardia/fibrillation. We have many powerful knowledge and tools,
      but at the same time, know well some limitations peculiar to individual therapy
      for particular arrhythmias.

PMID- 19768922
TI  - [Alpha-glucosidase inhibitor for the prevention of type 2 diabetes mellitus: a
      randomised, double-blind trial in Japanese subjects with impaired glucose
      tolerance].
AB  - The detrimental effects of a sedentary lifestyle and poor dietary habits are
      having a significant negative impact on health statistics, with obesity and its
      attendant risks becoming a major problem in most developed nations, including
      Japan. Interventions which prevent or delay the development of type 2 diabetes
      have the potential to reduce the morbidity and mortality associated with the
      disease and, as a consequence, related healthcare costs. The study conducted to
      assess whether alpha-glucosidase inhibitor, voglibose could prevent type 2
      diabetes developing in high-risk Japanese subjects with impaired glucose
      tolerance (IGT). 1,780 eligible subjects received standard diet and exercise
      therapy, and 897 were randomised to receive voglibose and 883 placebo. The study
      was planned for treatment to be continued until participants developed type 2
      diabetes [primary endpoint; determined by bi-annual oral glucose tolerance tests
      (OG'Ts) as well as fasting blood glucose measured every 3 months] or
      normoglycaemia or for a minimum of 3 years, subject to the findings of an interim
      analysis. The interim analysis significantly favoured voglibose and end-of-study
      report involves individuals treated for an average of 48.1 weeks. Subjects
      treated with voglibose had a significantly lower risk for the progression to type
      2 diabetes than placebo (50/897 vs 106/881: hazard ratio 0.595). Also,
      significantly more subjects in the voglibose group achieved normoglycaemia
      compared with those in the placebo group (599/897 vs 454/881: hazard ratio
      1.539). Voglibose, in addition to standard care with diet and exercise, was
      effective in preventing the progression of IGT to type 2 diabetes and in
      increasing the proportion of individuals with normoglycaemia in high-risk
      Japanese subjects with IGT.

PMID- 19768923
TI  - [Clock genes].

PMID- 19768924
TI  - [Concept and definition of insomnia].
AB  - The definition of insomnia is surprisingly quite difficult. It is not possible to
      decide whether a person has insomnia just by the length of his sleep time. This
      is because there is a significant difference in how much sleep each person needs.
      Insomnia is a state in which the patient' s physical, psychological, and social
      activities are interfered with by a strong feeling of sleep deficiency upon
      waking in the morning. Insomnia is a symptom, not a name of a disease. In
      treatment of insomnia, it is not enough to just make the patient sleep by use of
      sleeping pills. It is essential to research what lies beneath the insomnia,
      identify the cause, and remove it.

PMID- 19768925
TI  - [Epidemiologic research on insomnia in the general Japanese populations].
AB  - This paper reviews epidemiologic research on insomnia of the general Japanese
      populations in the last 10 years. Nationwide studies, 3 for adults and 2 for
      adolescents, were conducted in communities to estimate prevalence of insomnia and
      examine associated factors with insomnia. For adults, prevalence of insomnia was
      estimated of 17.3 to 22.3% for men and 20.5 to 21.5% for women. The associated
      factors were identified: increasing age, gender, being unemployed, poor health
      status, being psychological stressed, less physical activities, and use of
      hypnotic medications and nightcap. For adolescents, they were 23.3% for boys and
      23.7% for girls. Gender, poor mental health, smoking, drinking, college-bound,
      and lifestyle (e.g., not eating breakfast, late bedtime, not involved in
      extramural activities) were suggested as the associated factors. These findings
      have contributed to enhance the social recognition about the importance of
      insomnia for the general population in Japan.

PMID- 19768926
TI  - [The guidelines for the evaluation and management of insomnias in Japanese
      primary care].
AB  - Insomnia is defined by a repeated difficulty with sleep initiation, duration,
      consolidation, or quality that occurs despite adequate sleep opportunity, a
      persistent sleep difficulty, and associated daytime impairment in the
      International Classification of Sleep Disorders, 2nd edition (ICSD-2). 11
      categories describe the most etiologies of insomnia in ICSD-2. Insomnia is
      primarily diagnosed by clinical evaluation through a careful, detailed medical,
      psychiatric, and thorough sleep history in primary care. Diagnosing the cause of
      insomnia is necessary before an appropriate treatment can be proposed. In the
      treatment of insomnia, the effectiveness of both pharmacotherapy using hypnotics
      and nonpharmacological therapy(sleep hygiene education, cognitive behavioral
      therapy) is demonstrated clearly in numerous studies.

PMID- 19768927
TI  - [Daily phase adjustment of human sleep-wake cycle].
AB  - In humans, studies using temporal isolation unit have indicated that (1) bright
      light is a dominant zeitgeber in human circadian systems and (2) period of
      endogenous circadian rhythms is longer than 24 h. The human circadian systems
      have at least two unique features. First is an internal desynchronization in
      which period of core body temperature rhythm and sleep-wake cycle free-run with
      different periods. Internal desynchronization indicates that the human circadian
      system consists of two different oscillators. One has a circadian period of about
      25 h and drives the rhythms in rectal temperature and melatonin, and the other
      has a period longer than 30 h and drives the sleep-wake cycle. Second feature is
      non-photic entrainment of sleep-wake cycle to a strict social schedule (so called
      partial entrainment). In this review, we summarize and update the two oscillator
      model based on recent evidence obtained by sleep-wake schedule and physical
      exercise experiments under temporal isolation facility.

PMID- 19768928
TI  - [Pathophysiology of insomnia].
AB  - Insomniacs generally report not only sleep-related symptoms such as difficulty in
      initiating, maintaining, obtaining sufficient restorative sleep, but also
      experience various daytime impairment reflective of sleep deficits. Although
      pathophysiology of insomnia remains to be explored, physiological hyperarousal
      evidenced by cognitive, endocrine, and neurophysiologic variables has been
      revealed to be involved in onset and development of insomnia. Patients with
      insomnia also suffer from cognitive impairment. Characteristically, they report
      their sleep and psychoperformance to be worse than are objectively measured. This
      "perceived" deficit is exactly what aggravates the QOL of insomniac patients and
      let them fall in a vicious cycle. Insomnia is often induced by stress events, and
      is assumed to develop by 3Ps, predisposing, precipitating and perpetuating
      factors. Concept and diagnostic criterion of insomnia are still fluctuating.
      There is a need for clarification of pathophysiology of insomnia for development
      of efficient treatment skills and critical prevention of chronic insomnia.

PMID- 19768929
TI  - [Molecular mechanisms of insomnia].
AB  - Prostaglandin (PG) D2 and adenosine are potent endogenous somnogens and their
      sleep-inducing mechanisms are well characterized. We examined the contribution of
      these somnogens to physiological sleep by the combination of pharmacological
      tools and gene-knockout (KO) mice. Complete insomnia was observed in wild-type
      mice after an intraperitoneal injection of SeCl4, an inhibitor of PGD synthase
      (PGDS), or caffeine, an antagonist of adenosine A2A receptors. The SeCl4-induced
      insomnia was not observed in PGDS- or DP1 receptor-KO mice and the caffeine
      induced insomnia, in A(2A) receptor-KO mice. A DP1 antagonist, ONO-4127Na,
      reduced sleep of rats by 30% during infusion into the subarachnoid space of the
      basal forebrain. These results indicate that the PGD2/ adenosine system plays a
      critical role in the regulation of physiological sleep.

PMID- 19768930
TI  - [Primary insomnia].
AB  - Primary insomnia is relatively common. According to The International
      Classification of Sleep Disorders, primary insomnia is a syndrome mainly composed
      of psychophysiological insomnia, paradoxical insomnia and idiopathic insomnia.
      Primary insomnia is difficulty initiating sleep (sleep onset insomnia),
      difficulty maintaining sleep (mid-sleep awakening, early morning awakening) or
      chronic non restorative sleep, which persist longer than three weeks despite
      having adequate opportunity for sleep and result in impaired daytime functioning.
      Primary insomnia is not explained by currently known psychiatric disorders,
      medical conditions, substance use disorders. Primary insomnia is a non-organic,
      unknown etiology, middle-aged female predominant sleep disturbance. Recent
      findings suggest the hyperarousal hypothesis of primary insomnia. In the near
      future, non restorative sleep might be excluded from the definition of primary
      insomnia.

PMID- 19768931
TI  - [Circadian rhythm sleep disorders].
AB  - Circadian system is master clock of daily sleep-wake cycle. It is able to create
      periodic activity with a period of almost 24 hours autonomously, and is able to
      entrain itself to day-night cycle of environment using with daily change of
      sunlight as time clue. Circadian rhythm sleep disorders (CRSDs) are defined as
      sleep disorders caused by misalignment between internal circadian clock and
      social schedule. Insomnia, hypersomnia, headache or intestinal symptoms are
      common complaints of CRSD patients, and these symptoms may deteriorate patients'
      social function. Jet lag disorder and shift work disorder are originated by acute
      shift of social schedule that exceed ability of circadian entrainment. However,
      pathophysiology of other CRSDs are not fully cleared. Treatments of CRSDs aim to
      facilitate circadian entrainment to desirable schedule with time clues at proper
      timing of circadian system. Bright light therapy (BLT) and melatonin
      administration are effective. Hypnotic administration is not effective in most
      cases.

PMID- 19768932
TI  - [Insomnia associated with psychiatric disorders].
AB  - Most psychiatric disorders, such as schizophrenia, mood disorders, or neurotic
      disorders are associated with sleep disorders of various kinds, among which
      insomnia is most prevalent and important in psychiatric practice. Almost all
      patients suffering from major depression complain of insomnia. Pharmacological
      treatment of insomnia associated with major depression shortens the duration to
      achieve remission of depression. Insomnia has been recently reported to be a risk
      factor for depression. In patients with schizophrenia, insomnia is often an early
      indicator of the aggravation of psychotic symptoms. Electroencephalographic sleep
      studies have also revealed sleep abnormalities characteristic to mood disorders,
      schizophrenia and anxiety disorders. A shortened REM sleep latency has been
      regarded as a biological marker of depression. Reduced amount of deep non-REM
      sleep has been reported to be correlated with negative symptoms of schizophrenia.
      Recently, REM sleep abnormalities were found in teenagers having post-traumatic
      stress disorder after a boat accident. Although these facts indicate that
      insomnia plays an important role in the development of psychiatric disorders,
      there are few hypotheses explaining the cause and effect of insomnia in these
      disorders. Here, we reviewed recent articles on insomnia associated with
      psychiatric disorders together with their clinical managements.

PMID- 19768933
TI  - [Heart failure].
AB  - It seems that the causes of the insomnia are dyspnea and an orthopnea in the
      heart failure patient. But, only such a fit is not the cause of the insomnia
      because it complains about the insomnia even if heart failure is slight. An
      obstructive sleep apnea (OSA) is the risk of the heart failure. A heart failure
      patient often complicates a central sleep apnea (CSA) and a Cheyne-Stokes
      respiration (CSR), and has much sleep fragmentation and difficulty maintaining
      sleep. And sleep disorders are sometimes started by the medications such as the
      cardiovascular system agent thing; beta blocker and the statins. Sleep disorders
      represent a major challenge in terms of differential diagnosis in heart failure
      patients. This is particularly relevant to insomnia and sleep disordered
      breathing (SDB) such as OSA, CSA and CSR. Thus, expending the knowledge on both
      insomnia and SDB may contribute to improve medical quality among physician.

PMID- 19768934
TI  - [Chronic obstructive pulmonary disease (COPD)].
AB  - Insomnia is common in many patients with chronic obstructive pulmonary disease
      (COPD). The causes of insomnia are sleep induced pathophysiological effect of
      COPD itself, COPD comorbidities and the presence of coexisted obstructive sleep
      apnea. Sleep has profound adverse effects on respiration and gas exchange in
      patients with COPD. There are several mechanisms underlying oxygen desaturation
      during sleep. They include decreased functional residual capacity, decreased
      ventilatory responses to hypoxia and hypercapnia, impaired respiratory mechanical
      effectiveness, respiratory muscle fatigue, decreased respiratory drive, and
      increased upper airway resistance. COPD comorbidities include DM, cardiovascular
      diseases, osteoporosis, depression, and GERD. The coexistence of COPD and sleep
      apnea-hypopnea syndrome has been denominated "overlap syndrome".

PMID- 19768935
TI  - [Insomnia in diabetes].
AB  - Previous studies have shown that several physiological and psychological
      conditions, such as hyperglycemia, diabetic neuropathy, sleep apnea syndrome and
      depression, may cause sleep disturbances, insomnia in diabetic patients. On the
      other hand, epidemiological evidences are indicating that chronic partial sleep
      loss may increase the risk of diabetes. Laboratory studies have shown that sleep
      restriction is associated with an increase in sympathetic nervous activity and a
      decrease in insulin sensitivity without adequate compensation in beta-cell
      function, resulting in an impact on glucose homeostasis and an elevated risk of
      diabetes. Sleep curtailment is also associated with a dysregulation of the
      neuroendocrine control of appetite, with a reduction of the satiety factor,
      leptin, and an increase in hunger-promoting hormone, ghrelin. The adverse impact
      of sleep deprivation on energy homeostasis is likely to be driven by increased
      activity of neuronal populations expressing in orexin system that promotes
      waking, feeding and energy-expenditure.

PMID- 19768936
TI  - [Hypertension].
AB  - People are sleeping less in modern societies. It is said that short duration of
      sleep could play a role in the etiology of not only diabetes mellitus (DM) but
      also hypertension. Sleep disorders inducing sleep fragmentation and sleep
      deprivation, such as insomnia, obstructive sleep apnea syndrome (OSAS), and
      periodic limb movement disorder (PLMD), have been suggested to be independent
      risk factors for hypertension. OSAS is associated with a range of cardiovascular
      complications, in particular hypertension. All of hypertensive patients should be
      routinely screened for possible sleep disorders.

PMID- 19768937
TI  - [Chronic renal failure (hemo-dialysis patients)].
AB  - The feature of a dialysis patient's sleep disorder is that deviation with a
      feeling of subjective sleep and an objective sleep disturbance is large, and
      subjective symptoms are scarce considering serious sleep disorders. The feature
      of a dialysis patient' s sleep disturbance is characterized by increase in time
      to awake on bed and the fragmentation of sleep, which lead to reduction in
      sleeping hours. The prevalence of SAS (sleep apnea syndrome) in the dialysis
      patient is several times higher compared with the commoner. The prevalence of RLS
      (restless legs syndrome) in Japanese dialysis patient was almost even with
      Westerners patient. Otherwise it tends to underestimate sleep disturbance, our
      questionary survey revealed high prevalence of subjective sleep complaints in
      dialysis patients. The realities of dialyzed patient' s sleep disturbance might
      be more serious than we think.

PMID- 19768938
TI  - [Insomnia in children].
AB  - This article reviewed the insomnia in children, according to the second edition
      of the international classification of sleep disorders. In addition, Yonaki
      (sleep-related night time crying) and the consensus statement on pharmacologic
      management of insomnia in children and adolescents were introduced. Furthermore,
      a novel clinical entity-asynchronization-, parts of whose symptoms were
      presumable due to the behaviorally induced insufficient sleep syndrome due to
      inadequate sleep hygiene, was also introduced.

PMID- 19768939
TI  - [Insomnia in old age].
AB  - Alterations of sleep structure with aging are attributed to change of circadian
      sleep-wake system and decrease of daytime activity with aging. Prevalence of
      insomnia and use of sleeping pills increases with age. Physical and psychiatric
      conditions play important roles in poor sleep in old age, and restless legs
      syndrome and sleep disordered breathing increase with aging as well. Early and
      appropriate intervention to insomnia will contribute to improvement of health and
      quality of life in the elderly.

PMID- 19768940
TI  - [Self-report assessment: questionnaires and sleep logs/diaries].
AB  - Insomnia is defined by a repeated difficulty with sleep initiation, duration,
      consolidation, or quality that occurs despite adequate time and opportunity for
      sleep and results in some form of daytime impairment in ICSD-2. An adequate
      evaluation of persistent insomnia requires detailed historical information as
      well as medical, psychological, and psychiatric assessment. Sleep logs,
      questionnaires, and other self-reports devices are useful to gather preliminary
      information about the nature of insomnia and its potential contributing factors.
      The Pittsburgh Sleep Quality Index has been applied in a variety of settings to
      measure sleep quality. Sleep logs/diaries are widely employed in clinical
      research and practice. These measures can be used to guide and enhance the sleep
      and medical histories taken by the clinician.

PMID- 19768941
TI  - [Polysomnography (PSG)].
AB  - By definition, insomnia entails a subjective component relating to the perception
      of poor sleep, which may and may not be supported by objective evaluation of
      sleep. Although polysomnography (PSG) is the objective method that provides a
      comprehensive measurement of sleep and is essential in diagnosing many sleep
      disorders, it is not usually necessary in the assessment of an insomnia
      complaint. Recent practice parameters for the evaluation of insomnia published by
      American Academy of Sleep Medicine states that PSG is not indicated for routine
      evaluation of chronic insomnia. PSG should be considered in the situations where
      the patient presents with pathologic levels of sleepiness, reported symptoms of
      other sleep pathologies (e.g., sleep-disordered breathing, periodic limb
      movements, parasomnias).

PMID- 19768942
TI  - [Multiple sleep latency test (MSLT) and maintenance of wakefulness test (MWT)].
AB  - To define and evaluate sleepiness thoroughly has not yet completely established
      because of its multidimensional aspects of character. Multiple sleep latency test
      (MSLT) and maintenance of wakefulness test (MWT) have been the important tools to
      assess sleepiness in the research and clinical settings, although they have
      several limitations and pitfalls. The coverage by the National Health Insurance
      of MSLT, since April 1, 2008, in Japan, so far not MWT, would extend the
      diagnosis and care of sleep disorders concerning excessive daytime sleepiness
      including narcolepsy and idiopathic hypersomnia. The relevant and appropriate use
      of these modalities should be always considered in line with clinical history,
      medical information and judgment.

PMID- 19768943
TI  - [Actigraphy in sleep medicine and sleep research].
AB  - Actigraphy is a method that utilizes a miniaturized computerized wristwatch-like
      device to monitor and collect data generated by body movements over extended
      periods of time. It allows estimation of sleep and wakefulness based on motor
      activity. It provides a noninvasive, objective, and longitudinal method for the
      diagnostic and post-treatment evaluation of patients with sleep disorders in the
      ambulatory setting. It has been used for researchers to study sleep disturbances
      in a variety of populations, most frequently for the evaluation of insomnia,
      paradoxical insomnia, and circadian rhythm sleep disorders. In addition, it is
      particularly useful in populations where polysomnography would be difficult to
      record, such as in patients with dementia and delirium. Actigraphy should be
      extensively carried out in sleep medicine as well as sleep research.

PMID- 19768944
TI  - [Review of the usage of benzodiazepines].
AB  - Benzodiazepines are often prescribed because of their excellent efficacies,
      safety, and low risks of addiction and tolerance. In this paper, we outline their
      characteristics, usages and side effects. Benzodiazepines are classified into 4
      types, according to their half lives: ultra-short acting, short acting, medium
      acting, and long acting. When clinicians choose benzodiazepines, their half
      lives, types of insomnia, and patient's ages and daily livings must be
      considered. Clinicians should also take cautions for their adverse effects, i.e.,
      carry-over, withdrawal, and muscle relaxant.

PMID- 19768945
TI  - [Barbiturates as hypnotics].
AB  - Barbiturates had been playing an important role in treating insomnia for more
      than 100 years. To date, benzodiazepines and related compounds seem to be
      superseding the role of barbiturates because of their relative safeness. In this
      article, a brief summary on barbiturates as hypnotics is described including the
      history of development, mechanism of action, and disadvantageous pharmacological
      properties that limit application as sleep-inducing medication. Unrecognized
      problems concerning barbiturate prescription in Japan are also discussed.

PMID- 19768946
TI  - [Novel insomnia drugs, including drugs currently under development].
AB  - Insomnia has mainly been treated with the hypnotic benzodiazepine (BZ). Recent
      studies have revealed the role and mechanisms of BZ receptors and have led to the
      development of non-BZ hypnotics. The chemical structures of non-BZ hypnotics
      differ from that of BZ; these hypnotics selectively bind to the omega 1 receptor
      of the gamma-aminobutyric acid (GABA)-BZ receptor complex. Because the omega 2 BZ
      receptors have adverse effects such as muscle relaxant actions, non-BZ hypnotics
      have lesser adverse effects than BZ. Antipsychotics, antidepressants, and
      antihistamines are also used for the treatment of insomnia in patients with other
      medical problems such as schizophrenia and depression. Currently, novel hypnotics
      are being developed with the manipulation of neurotransmitters and non-GABAergic
      receptors such as the melatonin and serotonin receptors.

PMID- 19768948
TI  - [Nonpharmacologic treatment for insomnia].
AB  - Nonpharmacologic treatment for insomnia occupies an important position on the
      treatment of insomnia. It is necessary to educate the patient on sleep hygiene to
      adjust the unappropriate sleep pattern. Within methods of relaxation, autonomy
      training and biofeedback method are methods using muscle relaxation to achieve
      psychological balance. Morita therapy is a method to accept insomnia as it is,
      and give guidance on the patient's life activity in a constructive way. It is
      important to listen carefully to the patient's life background and choose
      treatment based on that information. For this, an appropriate construction of a
      doctor-patient relationship is essential.

PMID- 19768947
TI  - [A novel therapeutic drug: ramelteon].
AB  - Current treatment of insomnia with hypnotics, GABA(A) receptor modulators,
      induces various side effects, including cognitive impairment, motor disturbance,
      dependence, tolerance, hang-over, and rebound insomnia. Ramelteon (Rozerem) is an
      orally active, highly selective melatonin MT1/MT2 receptor agonist. Unlike the
      sedative hypnotics that target GABA(A) receptor complexes, ramelteon is a
      chronohypnotic that acts on the melatonin MT1 and MT2 receptors, which are
      primarily located in the suprachiasmatic nucleus. Ramelteon has demonstrated
      sleep-promoting effects in clinical trials, and coupled with its favorable safety
      profile and lack of abuse potential or dependence, this chronohypnotic provides
      an important treatment option for insomnia.

PMID- 19768949
TI  - [Cognitive behavior therapy].
AB  - Insomnia is one of the most frequently encountered disorders in general clinical
      practices. At present, the most commonly used therapy for insomnia is
      pharmacotherapy. There are some problems in pharmacotherapy such as side effects.
      Therefore nonpharmacological therapy for insomnia is needed. The cognitive
      behavior therapy for insomnia (CBT-I) is a nonpharmacological therapy attracting
      attention most. CBT-I not only alleviates insomnia symptoms in patients but also
      enables them to reduce/discontinue the use of hypnotics. I reviewed a study about
      the effectiveness of CBT-I and commented the future directions of CBT-I.

PMID- 19768950
TI  - [Bright light therapy].
AB  - Bright light is a treatment of choice for seasonal affective disorder. Other
      indications for bright light therapy have also been tested. These include
      circadian rhythm sleep disorders, early-morning awakening or sleep-maintenance
      insomnia in elders and behavioral disturbance or insomnia in organic dementia. In
      these sleep disorders, the pattern of sleep-wake is misaligned with the patient's
      circadian system or the external environment, resulting in insomnia.
      Appropriately-timed exposure to bright light can shift the sleep-wake cycle to
      earlier or later times, in order to correct for misalignment between the
      circadian system and the desired sleep-wake schedule. Evidence of the efficacy of
      bright light was so limited. Further research is needed to determine guidelines
      for the appropriate timing and safe use of bright light therapy.

PMID- 19768951
TI  - [Restless legs syndrome].
AB  - Restless legs syndrome has been recognized to be a common disorder as one of the
      sleep disturbances. The main symptom is an unpleasant and uncomfortable sensation
      frequently localized in the leg between the knee and the ankle. Patients find the
      nature of the discomfort difficult to describe and use words like creeping,
      pulling, stretching, restless sensations, aching and even pain. The authors
      report signs, symptoms, epidemiology, pathogenesis, treatment of the syndrome in
      this paper.

PMID- 19768952
TI  - [Insufficient sleep syndrome and QOL].
AB  - Sleepiness, the mood state, and quality of life (QOL) were compared in patients
      with insufficient sleep syndrome (ISS), between before and after treatment.
      Concerning the profile of mood states(POMS), the score of the V scale for "vigor"
      was significantly low, and the score of the C scale for "confusion" was
      significantly high. The primary treatment was life guidance. After treatment, the
      sleep time was significantly prolonged due primarily to going to bed earlier, and
      while the score on the Epworth sleepiness scale(ESS) decreased significantly. The
      scores of the V and C scales of the POMS were significantly improved after
      treatment but were still lower than in the control group. On the QOL26,
      significant improvements were observed in all items after treatment.

PMID- 19768953
TI  - [Potential therapeutic targets for diabetic nephropathy].
AB  - Diabetic nephropathy has emerged as the leading cause of end-stage renal disease.
      Intensive control of blood glucose and pressure has been the mainstay for the
      treatment of diabetic nephropathy and provided favorable evidence in slowing
      disease progression. However, current therapeutic regimens have not demonstrated
      satisfactory prevention of the nephropathy thus novel therapeutic agents are
      urgently needed. In diabetic conditions, multiple mechanisms have been implicated
      in glucose-mediated microvascular damage leading to nephropathy; activation of
      protein kinase C, accumulation of inflammatory mediators and advanced glycation
      end products, generation of reactive oxygen species, and other biochemical
      abnormalities. In turn, inhibiting these pathological mechanisms may represent a
      potential therapy for diabetic nephropathy. This review discusses current
      concepts innovel targeted therapy for diabetic kidney complications.

PMID- 19768954
TI  - LTACs to pay for CMS' error. Agency to revise relative weights rule for '09, '10.

PMID- 19768955
TI  - AMGA's profits down. Form 990 shows revenue, expenses up.

PMID- 19768956
TI  - Minnesota showdown. Steeper job cuts expected if Pawlenty doesn't relent.

PMID- 19768957
TI  - On the same wavelength. Group makes progress in data-transmission standards for
      home health devices.

PMID- 19768958
TI  - [Muscle satellite cells and regulation of recovery potential of the muscles].
AB  - Major aspects of the biology of muscle satellite cells are reviewed: the
      identification, origin in early development, mechanisms of self-renewal mediated
      by asymmetric divisions, content in different muscle types and in different
      ontogenetic stages, role of control genes of the Pax family (in particular, Pax7)
      and their products in proliferation control, and involvement of growth factors
      (HGF, FGF, IDF, and TGF-beta) in the activation of these cells after muscle
      damage. The characteristics of the early stages of myogenic differentiation of
      activated satellite cells along the pathway similar to muscle formation in
      embryonic development are discussed.

PMID- 19768959
TI  - [Analysis of spermatogenesis in senescence-accelerated mice].
AB  - A comparative analysis of age-related dynamics of spermatogenesis has been
      performed in mutant mouse lines predisposed or resistant to accelerated
      senescence (SAMP1 and SAMR1 respectively). The results show that quantitative and
      morphohistological trends in the development of sperm cells and Sertoli cells in
      both lines are similar in both lines. Their comparison with data obtained in our
      previous studies (Zakhidov et al., 2001; Gordeeva et al., 2001) shows that sharp
      quantitative and qualitative changes in the structure of the spermatogenic system
      have occurred in senescence-accelerated mice of new generations, which confirms
      the fact of dynamic instability of the germinal lineage. The role of stem
      spermatogonial cells in restoration of spermatogenesis in animals reaching the
      critical age is discussed.

PMID- 19768960
TI  - [The effect of the parameters of biolistic transformation of spring barley
      (Hordeum vulgare L.) on the level of transient expression of GFP reporter gene].
AB  - The effect of the parameters of biolistic transformation (rupture disk pressure
      of helium, vacuum pressure, stopping screen to target tissue distance, material
      (gold or tungsten) and size of particles, and duration of explant culturing
      before bombardment) on the level of transient expression of GFP reporter gene was
      studied in barley embryos. The highest transient expression was observed after
      explant preincubation for 12-14 days and bombardment with 1 microm gold particles
      at the helium pressure of 61.24-74.85 atm, vacuum pressure of 0.064 atm, and
      distance to target of 9 cm.

PMID- 19768961
TI  - [Evaluation of soil microbial communities in two types of Siberian forest
      ecosystems].
AB  - Microbial respiration and biomass were evaluated in soils of the Ermak Tree
      Nursery and Pogorel'skii Forest under different coniferous species. The degree of
      disturbance of each biocenosis was determined from the metabolic coefficient
      (qCO2). The microbial investigation demonstrated a lower resistance to ecological
      factors of the tree nursery biocenosis as compared to those of the Pogorel'skii
      Forest.

PMID- 19768962
TI  - [The role of hormonal balance in plant adaptation to flooding].
AB  - The effect of flooding on the growth parameters and hormonal dynamics (auxins,
      abscisic acid, cytokinins, gibberellins, and ethylene) has been studied in a
      vegetation experiment on the leaves of wheat (Triticum aestivum L.) and oat
      (Avena sativa L.). Growth inhibition during flooding in both species was due to
      the accumulation of abscisic acid and ethylene, while the repair processes were
      due to the increased level of auxins, cytokinins, and gibberellins. The
      difference in the hormonal response in wheat and oat to flooding, in particular,
      the degree and timing of accumulation of abscisic and indoleacetic acids and
      different dynamics of the level of cytokinins and gibberellins, induced their
      different physiological response, which determined the level of their resistance.
      The growth control of cereals during flooding as well as the hormonal dynamics
      are proposed to rely on the strategy of plant ontogenetic adaptation.

PMID- 19768963
TI  - [Seasonal patterns of life cycle of ground beetle Carabus nitens (Coleoptera,
      Carabidae) in southern tundra].
AB  - Seasonal dynamics of activity and demographic structure of Carabus nitens in the
      forest-tundra and southern tundra of the Kanin Peninsula was studied. In the
      northernmost range, the species has a one-year life cycle with reproduction in
      the early season and summer larvae. C. nitens demonstrated elongated period of
      development from egg to imago compared to the temperate zone in the polar region.
      At the same time, over-wintered beetles rapidly matured and the reproduction
      period was reduced to three decades. This synchronizes larval development and the
      young generation emergence. The northern populations have increased life span of
      imago, which leads to repeated postwinter reproduction during several seasons. As
      a result, the abundance of the northern C. nitens populations remains high.

PMID- 19768964
TI  - [Comparative analysis of the effect of endogenous antibiotic defensin NP-1 and
      aminoglycoside antibiotic gentamicin on synaptic transmission in receptors of the
      frog vestibular apparatus].
AB  - The effect of human and rabbit neutrophilic defensins NP-1 and amonoglycoside
      antibiotic gentamicin on the synaptic transmission in the afferent synapse of
      isolated vestibular apparatus of the frog has been comparatively studied. Both
      defensins proved active in the concentration range of 0.0001 to 1 nM and
      efficiently decreased the impulse frequency in the afferent nerve fibers in a
      concentration-dependent manner. No significant differences in the efficiency of
      rabbit and human defensin NP-1 have been revealed in these experiments.
      Gentamicin also had an inhibitory effect on the afferent discharge in the
      concentration range of 10-500 microM (0.5-25 mg/kg). The inhibitory effect of
      gentamicin on the impulse activity of the vestibular nerve was observed at
      therapeutic doses. The excitatory effect of the putative neurotransmitter L
      glutamate was considerably inhibited by defensin NP-1. These findings suggest
      that the mechanism of defensin action involves a modification of the synaptic
      transmission the hair receptor and is mediated by L-glutamate.

PMID- 19768965
TI  - [The relationship between the structure of dermorphines and their
      thermoregulatory activity].
AB  - The effect of structural modifications in the molecule of dermorphin on the
      functional state of thermoregulation of rats under cold, neutral, and hot
      environment has been studied. Thermoregulatory and vasomotor activities of 43
      peptides (fragments and analogs) were tested in comparison with dermorphin. The
      role of amino acid residues in the second, third, fourth, and sixth positions was
      studied. Different fragments of dermorphin molecule proved to underlie different
      types of thermoregulatory activity (the hypothermic effect was observed in the N
      terminal tripeptide, while the N-terminal hexapeptide had the vasodilator
      activity), and targeted modification of dermorphin molecule makes it possible to
      separate the hypothermic, vasodilatory, and vasoconstrictive activities. It was
      proposed that dermorphin is the ligand not only for micro-opioid receptors.

PMID- 19768966
TI  - [The mechanism of carbon isotope fractionation in photosynthesis and carbon
      dioxide component of the greenhouse effect].
AB  - The relationship between the global climate warming, which is largely induced by
      increased CO2 atmospheric concentration, and the changes in carbon isotope
      fractionation in plants was explained in terms of the previously proposed
      oscillatory mechanism of photosynthesis, according to which CO2 assimilation and
      photorespiration are two reciprocally coupled oscillating mechanisms controlled
      by ribulose bisphosphate carboxylase/oxygenase switches. This explanation is
      confirmed by the changes in carbon isotope fractionation in the annual rings of
      trees and demonstrates that the light carbon isotope 12C enrichment before 1990s
      resulted from increased photosynthetic assimilation of CO2. The subsequent sharp
      13C enrichment of the tree ring carbon until the present time suggests that the
      compensatory role of photosynthesis in boreal forests has been lost for the
      global climate.

PMID- 19768967
TI  - [Symbiotic microflora in fishes of different ecological groups].
AB  - Published data on the taxonomic composition of the intestinal bacterial flora in
      fishes living under different conditions (marine and freshwater fishes) and
      differing in the type of feeding are reviewed. The results confirm the conclusion
      that the composition of intestinal microflora differs depending on fish ecology.
      A limited number of bacterial taxa found in the intestines of some fish species
      may be evidence not only for a low diversity of these bacteria but also for
      insufficient knowledge about them. Considerable differences in the composition of
      intestinal microflora in marine and freshwater fishes are described.

PMID- 19768968
TI  - [Species composition and structure of testate amoebae community in a sphagnum bog
      at the initial stage of its formation].
AB  - A total of 42 species and forms have been revealed in the testate amoebae
      community of a transitional bog at the initial stage of transformation into a
      typical sphagnum bog. A distinctive features of its species composition is
      dominance of widespread species Assulina muscorum. Arcella arenaria, Phryganella
      hemisphaerica, and Euglypha laevis in the absence of common sphagnobionts of the
      genera Nehela, Hyalosphenia, and Heleopera. Vertical heterogeneity of the
      community structure is weakly manifested, since dominant species are abundant in
      all horizons. The highest species richness is characteristic of the marginal
      community formed at the boundary between a sphagnum quagmire and a reed grass
      dominated fen.

PMID- 19768969
TI  - [Spatial structure of soil macrofauna in the northern Caspian clay semidesert].
AB  - Long-term soil-zoological studies have been performed in the Northern Caspian
      clay semidesert, at the Dzhanybek station of the Institute of Forest Science,
      Russian Academy of Sciences. Their results are summed up, and specific features
      of the spatial distribution of invertebrates (macrofauna) in soils constituting a
      three-component solonetz complex are discussed.

PMID- 19768970
TI  - [Annual variation in hematological indices in a fluctuating population of bank
      vole (Clethrionomys glareolus)].
AB  - The quantitative and structural hematological indices were studied in bank vole
      in different reproductive states (overwintered individuals, mature
      underyearlings, and immature underyearlings) in different years corresponding to
      different phases of the population cycle. The annual changes in certain
      hematological indices have been revealed for each reproductive state irrespective
      of the population cycle phase.

PMID- 19768971
TI  - [Assessment of serum IgG activity correlation against cyclic citrullinated
      peptide antibodies, topoisomerase I and centromere proteins in Mexican patients
      with progressive systemic sclerosis].
AB  - OBJECTIVE: To evaluate sera titers for antibodies anti-cyclic citrullinated
      peptide and their correlation against sera levels of anti-topoisomerase I and
      anti-centromere antibodies in Mexican patients with systemic sclerosis. PATIENTS
      AND METHODS: Consecutive outpatients with systemic sclerosis who attending to
      rheumatology clinic at a second level hospital facility. The antibodies anti
      cyclic citrullinated peptide, anti-topoisomerase I and anti-centromere were
      determined by enzymatic immunoassay (ELISA). STATISTICAL ANALYSIS: Spearman for
      correlation between numerical variables with nonparametric distribution. Fisher
      exact test or chi2 to compare proportions and Student t test for dimensional
      variables. RESULTS: Thirty female patients were included; aged 53 +/- 13, the
      disease duration at the time of the study was 10 +/- 9. Twenty-three patients
      (77%) exhibited diffuse disease. Anti-centromere, anti-topoisomerase I, and anti
      cyclic citrullinated peptide were detected in nine, nine and three patients
      respectively. The correlation analysis showed the independence of autoantibodies
      anti-centromere and anti-topoisomerase I with respect to the levels of anti
      cyclic citrullinated peptide. CONCLUSIONS: This study confirms the low frequency
      of anti-cyclic citrullinated peptide antibodies in patients with systemic
      sclerosis. A lack of correlation between autoantibodies considered as "mutually
      excluded" anti-topoisomerase I and anti-centromere, indicating that the analysis
      of the relevance for anti-cyclic citrullinated peptide in systemic sclerosis must
      include other clinical and serological variables.

PMID- 19768972
TI  - [Anesthesiologist's aptitude for peri-operative detection and treatment of latex
      allergy].
AB  - BACKGROUND: Latex allergy is the second cause of perioperative anaphylaxis.
      Anesthesiologists play a key role in opportune identification of risk factors, as
      well as clinical diagnosis and therapeutic management. OBJECTIVE: To evaluate the
      anesthesiologists aptitude to identify and treat latex allergy. PARTICIPANTS AND
      METHODS: Sixty-six anesthesiologists from five general hospitals located at
      Guadalajara, Jalisco, Mexico, were evaluated. Aptitude was determined by applying
      a validated structured instrument. Aptitude levels were measured by using an
      ordinal scale. Comparisons were performed using Mann Whitney U test. RESULTS:
      Anesthesiologist's global aptitude ranged from -2 to 27 with a median of 8 (from
      a maximum value in the scale of 40); frequencies by each category of the scale
      were: Random 48 (72.7%), Very bad 11 (16.7%), Bad 4 (6.1%) and Medium only 3
      (4.5%). Both Good and Very good categories registered no anesthesiologist. The
      relationship of this indicator with other variables did not reach statistical
      significance (KW 6.478; p = 0.16617). CONCLUSIONS: A suboptimal aptitude was
      identified among anesthesiologists regarding identification of latex allergy. A
      need to establish new strategies for educative intervention in order to improve
      this issue was identified.

PMID- 19768973
TI  - [Difficult-to-control asthma. A bibliographical review].
AB  - Difficult-to-control asthma is a disease that causes serious exacerbations, near
      fatal attacks, frequent hospitalizations, and needs chronic use of high doses of
      inhaled corticosteroids or daily oral corticosteroid therapy. On the basis of
      epidemiological studies, the risk factors for serious asthma are: female gender,
      high BMI, sensitivity to aspirin, gastro esophageal reflux, sinusitis, pneumonia
      history, and beginning of asthma symptoms in adult late age. It has been found
      that in severe asthma the inflammatory profile commonly changes with major
      participation of neutrophils, and evidence of destruction and remodelling. The
      first step in the care of these patients is an evaluation to determine that
      asthma is the right diagnosis. A systematic and rigorous evaluation helps to
      asses adequately the differential diagnoses, the comorbilities and the unusual
      triggers. The aim of the treatment is to achieve the best results with minimum
      adverse effects. New immunomodulatory therapies are needed for these patients
      management.

PMID- 19768974
TI  - [Urticaria pigmentosa: a current approach].
AB  - The term urticaria pigmentosa (UP) denotes a heterogeneous group of disorders
      characterized by abnormal growth and accumulation of mast cells (MC) in the skin.
      Symptoms result from MC chemical mediator's release, pathologic infiltration of
      neoplastic MC in tissues or both. Multiple molecular, genetic and chromosomal
      defects seem contribute to an autonomous growth, but somatic c-kit D816V mutation
      is more frequently found, especially in systemic disease. The aim of this paper
      is to provide a current overview for a better understanding of the symptoms
      associated with this disease, to describe its classification, recent advances in
      its pathophysiology and its treatment.

PMID- 19768975
TI  - [Scleroderma related to specific immunotherapy. A report of a case].
AB  - It has been described two main phenotypes of helper T cells. On activation, the
      immune system develops the most effective Th response. Whereas Th1 cells promote
      cell-mediate immunity against intracellular pathogens and an over expression
      could favor autoimmune diseases; Th2 cells develop humoral immunity against
      extracellular pathogens promoting allergic response. Normally, the two profiles
      coexist in the same individual with different grades of expression. Recently, it
      has been described a new subset: Th17, which is related to tissue injury in
      autoimmune diseases. Then, allergic and autoimmune diseases result from an
      unbalanced response of the immune system. Allergen-specific immunotherapy is the
      only curative treatment of a specific allergy, which leads to a life-long
      tolerance against allergens. There are no controlled studies about the
      effectiveness or risks associated with allergen-specific immunotherapy in
      patients with autoimmune disorders. On the other hand, scleroderma is an
      autoimmune chronic systemic disorder of unknown etiology characterized by excess
      collagen deposition in the skin and viscera, along with vascular injury. We
      report a girl with allergic asthma and with a second degree family history of
      systemic sclerosis who developed localized scleroderma during allergen specific
      immunotherapy. Because allergy vaccination alter the balance between effector and
      regulatory T-cell populations, which regulate immune tolerance, a positive family
      history of autoimmunity in first or second degree, could be a contraindication
      for allergen-specific immunotherapy.

PMID- 19768976
TI  - A new sesquiterpenoid coumarin from Ferula assafoetida.
AB  - The gum resin of Ferula assafoetida Linn. afforded one new sesquiterpene,
      asimafoetida 1 and three known sesquiterpenoid coumarins. The structure has been
      established from extensive 2D NMR spectral studies as 7'-[7-(1R,3S)-5-Hydroxy-6,6
      dimethyl-2-methylene-cyclohexyl]-9-methyl-9-pentenyl]oxy]-2H-1-benzopyran-2-one.
      The other three known compounds are ferulic acid, farnesiferol A and farnesiferol
      C.

PMID- 19768977
TI  - Antiproliferative activities of five Chinese medicinal herbs and active compounds
      in Elephantopus scaber.
AB  - Extracts and fractions prepared from five medicinal herbs used to treat cancer in
      Chinese folk medicine were tested for their antiproliferative activities on five
      cancer cell lines using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium
      bromide (MTT) assay. The MTT results revealed that the ethanolic extracts
      possessed stronger antiproliferative activities than the corresponding aqueous
      ones. The bioactive fractions of the ethanolic extracts were mostly found in n
      hexane and/or ethyl acetate fractions, which by TLC analysis were shown to
      contain terpenes and/or phenolic compounds. The ethyl acetate fraction from the
      ethanolic extract of Elephantopus scaber showed the highest effect with IC50
      values of less than 25 microg/mL on three susceptible cell lines, namely, PC-3
      (human prostate carcinoma cell), CNE (human nasopharyngeal carcinoma epithelial
      cell) and HL-60 (human acute promyelocytic leukemia cell). Further isolation and
      analysis of this fraction led to the identification of three sesquiterpene
      lactones, two flavonoids and five triterpenes. MTT results showed that the
      sesquiterpene lactones were the most effective group with IC50 values ranging
      from 0.9 to 7.5 microM while the flavonoids possessed moderate to strong effect
      with IC50 values ranging from 17.3 to 42.6 microM. However, the triterpenes
      displayed weak effect with IC50 values larger than 50 microM. Among the active
      compounds, deoxyelephantopin, a sesquiterpene lactone, exhibited the strongest
      effect on the PC-3, CNE and HL-60 cells, with IC50 values of 4.6, 2.6 and 0.9
      microM, respectively. Flow cytometric analysis showed that treatment with
      deoxyelephantopin caused subG-1 population augmentation in PC-3, CNE and HL-60
      cells, suggesting apoptosis was induced in these cells.

PMID- 19768978
TI  - Naturally occurring labdane diterpene and benzofuran from Globba pendula.
AB  - Phytochemical investigation on Globba pendula resulted in the isolation of a new
      naturally occurring 16-oxo-(8)17-12-labdadien-15,11-olide 1 and benzofuran-2
      carboxaldehyde 2. Other known compounds including isoandrographolide, indirubin,
      vanillin, vanillic acid, 2(3H)-benzoxazolone, as well as beta-sitosteryl-beta-D
      glucopyranoside, beta-sitosterol, and 7alpha-hydroxysitosterol were also
      isolated. The structures were established based on spectroscopic data and
      comparison with the literature. Furthermore, the compound isoandrographolide has
      demonstrated strong cytotoxic properties towards a panel of cancer cell lines
      (MCF-7, PC-3, and H-460) with the IC50 values of 7.9, 8.7, and 9.0 microM,
      respectively.

PMID- 19768979
TI  - VCD determination of the absolute configuration of stypotriol.
AB  - The absolute configuration of the pentacyclic ichthyotoxin stypotriol, a
      constituent of Stypopodium zonale, was deduced to be 3S,5R,8R,9R,10S,13S,14S-(-)
      1 by vibrational circular dichroism spectroscopy of the derived triacetate 2 in
      comparison to DFT B3LYP/DGDZVP calculations. Compound 2, C33H46O7 having 300
      electrons, is the largest natural product successfully studied by VCD to date.

PMID- 19768980
TI  - Bioactive steroidal sulfates from the ambulakrums of the Pacific starfish
      Lysastrosoma anthosticta.
AB  - Lysaketotriol (1) and lysaketodiol (2), along with two previously known
      polyhydroxylated steroidal sulfates (3, 4), were isolated from the ethanolic
      extract of ambulakrums separated from the arms of the starfish Lysastrosoma
      anthosticta (Sea of Japan). The chemical structures have been elucidated using 1D
      and 2D NMR spectroscopy (1H, 13C, DEPT, COSY-45, HSQC and HMBC) and mass
      spectrometry. Compound 1 produced moderate stimulation of lysosomal activity in
      mouse splenocytes and compounds 1-2 showed immunomodulatory activity.

PMID- 19768981
TI  - Role of modifier in microwave assisted extraction of oleanolic acid from Gymnema
      sylvestre: application of green extraction technology for botanicals.
AB  - This work highlights the development of a green extraction technology for
      botanicals with the use of microwave energy. Taking into consideration the
      extensive time involved in conventional extraction methods, coupled with usage of
      large volumes of organic solvent and energy resources, an ecofriendly green
      method that can overcome the above problems has been developed. The work compares
      the effect of sample pretreatment with untreated sample for improved yield of
      oleanolic acid from Gymnema sylvestre leaves. The pretreated sample with water
      produced 0.71% w/w oleanolic acid in one extraction cycle with 500 W microwave
      power, 25 mL methanol and only an 8 min extraction time. On the other hand, a
      conventional heat reflux extraction for 6 hours could produce only 0.62% w/w
      oleanolic acid. The detailed mechanism of extraction has been studied through
      scanning electron micrographs. The environmental impact of the proposed green
      method has also been evaluated.

PMID- 19768982
TI  - Phytochemical characterization of an adaptogenic preparation from Rhodiola
      heterodonta.
AB  - The phytochemical constituents of a biologically active, standardized, 80%
      ethanol extract of Rhodiola heterodonta were characterized. The extract was
      fractionated over a Sephadex LH-20 column to afford two main fractions
      representing two classes of secondary metabolites: phenylethanoids and
      proanthocyanidins. This fractionation facilitated the identification and
      quantification of individual compounds in the fractions and sub-fractions using
      HPLC, and LC-MS. The major compounds in the phenylethanoid fraction were
      heterodontoside, tyrosol methyl ether, salidroside, viridoside, mongrhoside,
      tyrosol, and the cyanogenic glucoside rhodiocyanoside A. These seven compounds
      comprised 17.4% of the EtOH extract. Proanthocyanidins ranged from oligomers to
      polymers based on epigallocatechin and gallate units. The main identified
      oligomeric compounds in the proanthocyanidin fraction were epigallocatechin
      gallate, epigallocatechin-epigallocatechin-3-O-gallate and 3-O-galloyl
      epigallocatechin-epigallocatechin-3-O-gallate, which constituted 1.75% of the
      ethanol extract. Tyrosol methyl ether, mongrhoside, and the two proanthocyanidin
      dimers were reported for the first time from this species in this study.
      Intraperitoneal injection of the 80% ethanol extract increased survival time of
      mice under hypoxia by 192%, as an indication of adaptogenic activity.

PMID- 19768983
TI  - Chemical composition and antimicrobial activity of wild garlic Allium ursinum of
      Bulgarian origin.
AB  - The chemical composition of fresh flowers from Allium ursinum (ramsons, bear's
      garlic, wild garlic) growing in Bulgaria has been studied. Thymidine (1),
      adenosine (2), astragalin (kaempferol-3-O-beta-D-glucopyranoside (3), kaempferol
      3-O-beta-D-glucopyranosyl-7-O-beta-D-glucopyranoside (4), kaempferol-3-O-beta-D
      neohesperoside (5), and kaempferol-3-O-beta-D-neohesperoside-7-O-beta-D
      glucopyranoside (6) were isolated from the n-butanol extract and identified by
      different spectroscopic and spectrometric methods. Thymine (7), uridine (8),
      uracil (9) and 5-chloro-uridine (10) were detected in the same extract by GC-MS.
      This is the first report of the occurrence of 1, 2, 4, 7 - 10 in the flowers of
      A. ursinum. GC-MS of the volatile components of fresh flowers and leaves from the
      same plant revealed a high content of sulfur compounds, some of which are
      reported for the first time for A. ursinum. The antimicrobial activities of
      extracts from fresh flowers and leaves of A. ursinum have been tested; some
      extracts exhibited moderate antifungal properties.

PMID- 19768984
TI  - Evaluation of the antioxidant and antimicrobial properties of in vitro cultured
      Drosera intermedia extracts.
AB  - Evaluation of the antioxidant activity of the methanol, water and n-hexane
      extracts of Drosera intermedia, determined by the Folin-Ciocalteau (F-C), trolox
      equivalent antioxidant capacity (TEAC) and oxygen radical antioxidant capacity
      (ORAC) assays showed that the methanol extract had the highest antioxidant
      activity (F-C: 378.6 +/- 31.5 micromol(GAE)/mg(extract); TEAC: 332.2 +/- 29.1
      micromol(TE)/mg(extract); ORAC: 64.7 +/- 7.8 micromol(TE)/mg(extract).
      Antimicrobial activity was tested against seven bacterial and eight yeast strains
      using the agar diffusion assay, followed by the determination of minimum
      inhibitory concentrations (MIC). All tested D. intermedia extracts demonstrated
      strong antimicrobial properties with a broad spectrum of activity. However, the n
      hexane extract exhibited much greater activity than water and methanol extracts.
      The most susceptible microorganisms to the n-hexane extract were Staphylococcus
      epidermidis ATCC 12228 and Candida albicans YP0175, for which a MIC value of 13.0
      microg/mL was scored.

PMID- 19768985
TI  - Determination of phytoestrogen composition in soybean cultivars in Serbia.
AB  - The growing clinical interest and use of soybean-based food products and extracts
      to increase dietary phytoestrogen intake have led to medical interest in the
      precise determination of the phytoestrogen composition of soybean products. We
      have analyzed the composition of these compounds in 20 domestic and introduced
      varieties of genetically non-modified soybean genotypes grown under the same
      agroecological conditions. The isoflavone content of soybeans cultivated in this
      region of Serbia has not been previously reported. The assays were performed,
      after extraction with methanol-water (8:2, v/v), by C18 reversed phase high
      performance liquid chromatography coupled with photodiode array detection. The
      total phytoestrogen concentration was found to be between 2.24 and 3.79 mg g(-1)
      dry bean weight. The total concentration of daidzein and its derivatives ranged
      from 0.96 to 1.82 mg g(-1), total glyciteines from 0.34-0.53 mg g(-1), and all
      genistein derivatives from 0.86-1.67 mg g(-1) dry bean weight. Given the high
      biological potency of phytoestrogens and their metabolic conversion products, our
      data suggest that phytoestrogen content screening could be a useful tool in the
      selection of soybean genotypes with improved health promoting characteristics.

PMID- 19768986
TI  - Antilonomic effects of Brazilian brown seaweed extracts.
AB  - The aim of this work was to investigate the hemolysis and blood clotting activity
      of Lomonia obliqua venom and the ability of some Brazilian marine algal extracts
      (Canistrocarpus cervicornis, Stypopodium zonale and Dictyota pfaffi) to
      antagonize such biological activities. L. obliqua caterpillars are dangerous to
      human beings and envenomation symptoms are characterized by hemorrhagic,
      hemolytic and blood clotting disorders, and acute renal failure, which sometimes
      lead to the death of the victims. Through in vitro experiments we have shown that
      L. obliqua venom is able to clot human plasma and hemolize human erythrocytes and
      that the coagulation activity of the venom is inhibited by the extracts of C.
      cervicornis, S. zonale and D. pfaffi. In contrast, C. cervicornis and S. zonale
      extracts did not inhibit the hemolytic activity of L. oblqua, as did the extract
      of D. pfaffi. These finding indicate that marine algae may be used as antivenoms
      or may contribute to the development of compounds with antilonomic effects.

PMID- 19768987
TI  - Rapid identification of two species of Peucedanum by high-performance liquid
      chromatography-diode array detection-electrospray ionization tandem mass
      spectrometry.
AB  - The fragmentation behaviors of the angular- and linear-type coumarins from
      Peucedanum praeruptorum Dunn and P. decursivum (Miq.) Maxim were simultaneously
      investigated by HPLC-DAD/ESI-MS(n). For more structural identification, the
      fragment ions were analyzed and some possible fragmentation pathways were
      proposed. Different positions and numbers of the substituent also led to
      different fragment behaviors. Two types of coumarins from P. praeruptorum and P.
      decursivum were structurally elucidated by these techniques. In addition, UV
      spectra were applied to support the MS analysis. This is the first time that the
      two types of coumarins from herbal extracts have been differentiated by HPLC
      DAD/ESI-MS(n). The method further illustrated the importance of the ESI-MS(n)
      technique in the identification of different types of coumarins and was applied
      for the rapid differentiation of the two herbs.

PMID- 19768988
TI  - Aaptamine alkaloids from the Vietnamese sponge Aaptos sp.
AB  - A series of aaptamines, including one new alkaloid (1), were isolated from the
      marine sponge Aaptos sp. collected in Vietnamese waters. The structure of 1 was
      elucidated using NMR and HRESIMS, as well as by chemical transformation of 1 to
      the previously known aaptamine and established as 3-N-morpholinyl-9
      demethyl(oxy)aaptamine. The isolated compounds showed a potential cancer
      preventive activity.

PMID- 19768989
TI  - Pancreatic lipase inhibitory alkaloids of Murraya koenigii leaves.
AB  - In the continuing search for newer pancreatic lipase inhibitors from plants, a
      total of 63 extracts from 21 different plants were screened to study their
      pancreatic lipase (PL) inhibitory activity in vitro. All three extracts (DCM,
      EtOAc and MeOH) of Murraya koenigii (L.) Spreng leaves (Rutaceae) exhibited
      antilipase activity greater than 80%. Further, bioactivity guided fractionation
      of the EtOAc extract led to the isolation of four alkaloids, namely mahanimbin,
      koenimbin, koenigicine and clausazoline-K, with IC50 values of 17.9 microM, 168.6
      microM, 428.6 microM and <500 microM, respectively. This study reports for the
      first time the PL inhibitory potential of carbazole alkaloids from plants.

PMID- 19768990
TI  - Recovery and purification of nicotine from waste tobacco by aqueous two-phase
      system/reverse extraction.
AB  - A two-step process has been developed for the purification of nicotine from waste
      tobacco using an aqueous two-phase system and solvent reverse extraction. The
      partitioning behavior of nicotine was investigated in an isopropyl
      alcohol/(NH4)2SO4 aqueous two-phase system. The effects of the addition of salt,
      pH and temperature on the partitioning behavior of nicotine were studied. The
      recovery rate of nicotine was 96.1% with a purity of above 99% when optimal
      conditions were used [(NH4)2SO4 25%, pH 9, temperature 35 degrees C, isopropyl
      alcohol 5 mL].

PMID- 19768991
TI  - Structure elucidation of acylsucrose derivatives from Atractylodes lanceae
      rhizome and Atractylodes rhizome.
AB  - The mass chromatographic fingerprints of the water extracts of Atractylodes
      rhizome and Atractylodes lancea rhizome were analyzed by LC-MS. Three new
      acylsucrose derivatives [2,6,3',6'-tetra(3-methylbutanoyl)sucrose (1), 2,4,3',6'
      tetra(3-methylbutanoyl)sucrose (2), and a mixture of 3',4',6'-tris(3
      methylbutanoyl)-1'-(2-methylbutanoyl)sucrose and 1',3',4',6'-tetra(3
      methylbutanoyl)sucrose (6)), along with three known acylsucroses (2,6,3',4'
      tetra(3-methylbutanoyl)sucrose (3), 2,4,3',4'-tetra(3-methylbutanoyl)sucrose (4)
      and a mixture of 2,3',6'-tris(3-methylbutanoyl)-1'-(2-methylbutanoyl)sucrose and
      2,1',3',6'-tetra(3-methylbutanoyl)sucrose (5)] were isolated as the marker
      compounds of Atractylodes rhizome and Atractylodes lancea rhizome. The structures
      of the compounds were elucidated by MS/MS analyses and NMR experiments.

PMID- 19768992
TI  - The composition of the essential oil from Cyperus distans rhizome.
AB  - The essential oil from the rhizomes of Cyperus distans L.f. obtained by
      hydrodistillation was analyzed by capillary GC and GC/MS techniques. Eight
      constituents were identified, representing 99.6% of the total oil. The major
      components of the oil were cyperene (47.6%), alpha-pinene (18.8%), 1,8-cineole
      (14.5%) and caryophyllene oxide (7.3%).

PMID- 19768993
TI  - Essential oil composition and enantiomeric distribution of fenchone and camphor
      of Lavandula cariensis and L. stoechas subsp. stoechas grown in Greece.
AB  - The essential oils from leaves and inflorescences of L. cariensis Boiss. and L.
      stoechas L. subsp. stoechas collected in Greece were analyzed by GC and GC/MS. In
      the inflorescences and leaves essential oils of L. cariensis the most abundant
      metabolite was camphor (51.8, 48.8% respectively), whereas in the essential oils
      of L. stoechas subsp. stoechas, the main constituents were fenchone (39.9, 21.0%
      respectively) and camphor (24.2, 26.3% respectively). Both enantiomers of camphor
      were present, whereas only (+) fenchone was detected.

PMID- 19768994
TI  - Chemical composition, olfactory evaluation and antioxidant effects of essential
      oil from Mentha x piperita.
AB  - The chemical composition of the essential oil from peppermint (Mentha x piperita
      L.) was analyzed by GC/FID and GC-MS. The main constituents were menthol (40.7%)
      and menthone (23.4%). Further components were (+/-)-menthyl acetate, 1,8-cineole,
      limonene, beta-pinene and beta-caryophyllene. Peppermint oil possessed
      antiradical activity with respect to DPPH (diphenyl picryl hydrazyl) and hydroxyl
      (OH*) radicals, exercising stronger antioxidant impact on the OH* radical. The
      concentrations required for 50% inhibition of the respective radical (IC50) were
      860 microg/mL for DPPH and 0.26 microg/mL for OH*. Peppermint essential oil
      demonstrated antioxidant activity in a model linoleic acid emulsion system in
      terms of inhibiting conjugated dienes formation by 52.4% and linoleic acid
      secondary oxidized products generation by 76.9% (at 0.1% concentration).

PMID- 19768995
TI  - Analysis of essential oils of Artemisia absinthium L. from Lithuania by CC,
      GC(RI), GC-MS and 13C NMR.
AB  - Different techniques have been utilized to determine the composition of Artemisia
      absinthum (wormwood) essential oil. The oil was fractionated on a silica gel
      column and each fraction analyzed by GC(RI), GC-MS and 13C NMR. This allowed the
      identification, for the first time in A. absinthium, of two diterpenes, 9-geranyl
      p-cymene and 9-geranyl-alpha-terpinene, and two homoditerpenes, 9-(15,16-dihydro
      15-methylene)-geranyl-p-cymene and 9-(15,16-dihydro-15-methylene)-geranyl-alpha
      terpinene. Chemical variability of A. absinthium essential oils from plants
      collected in the surroundings of Vilnius city over several years (1999-2007) was
      also shown. Chemical composition was determined by GC and GC-MS. Thujones
      (cis+trans, 10.2-36.3%) and trans-sabinyl acetate (9.8-39.2%) were the two
      predominant constituents of almost all the investigated oils (13 out of 15
      samples). The third major compound was myrcene (5.1-9.2%, in four samples), beta
      pinene (5.4-10.4%, in 5), linalool (4.7% in one), trans-sabinol (6.4%, in one)
      and 1,8-cineole (5.2-7.1%, in two). In one oil, the prevailing components were
      thujones (cis+trans, 11.2%), trans-sabinene hydrate (11.0%) and trans-sabinyl
      acetate (8.8%), while another sample was characterized by a large quantity of
      trans-sabinyl acetate (55.2%) and the absence of thujones.

PMID- 19768996
TI  - Chemical composition and antibacterial activity of the essential oil of Cordia
      verbenacea from the Venezuelan Andes.
AB  - The essential oil of Cordia verbenacea D.C. (Boraginaceae) that grows in Merida
      Venezuela was obtained by hydrodistillation from the aerial parts of the plant,
      yielding 0.21%. The oil was analyzed by GC-FID and GC-MS. Thirty one components
      which made up 94.3% of the oil were identified. The most abundant constituents
      found were: tricyclene (23.9%), bicyclogermacrene (11.7%), germacrene D (9.9%)
      and beta-caryophyllene (8.2%). Antibacterial activity determination was carried
      out according to the disc diffusion assay. Activity against Gram-positive
      bacteria Staphylococcus aureus ATCC 6538 and Enterococcus faecalis ATCC 29212, at
      a minimal inhibitory concentration (MIC) of 170 microg/mL and 200 microg/mL, was
      found.

PMID- 19768998
TI  - Chemical composition and antimicrobial activity of the essential oils of leaves,
      roots and bark of Glossocalyx staudtii.
AB  - The chemical composition of the essential oils obtained by hydrodistillation from
      air dried leaves, bark and roots of Glossocalyx staudtii Engl. grown in Gabon was
      analyzed by GC and GC-MS. The essential oil content was 0.84% (w/w), 0.28% (w/w),
      and 0.74% (w/w), respectively. The leaf oil was characterized by a high content
      of monoterpene hydrocarbons (64.8%), with beta-pinene (30.6%) and alpha-pinene
      (22.6%) as the major constituents. The oil obtained from the bark contained 30.5%
      of oxygenated monoterpenes with cryptone as the main constituent (11.5%) and
      28.9% of aliphatic compounds, with 9.3% of 2-tridecanone; in the roots oil, the
      main component was 2-tridecanone (55.2%). The antimicrobial activity of the oils
      was studied by means of the agar disc diffusion and broth microdilution methods.
      The Gram positive bacteria were the most sensitive to the essential oils. A
      significant anticandidal effect of the bark essential oil was observed.

PMID- 19768997
TI  - Composition and antimicrobial activity of the leaf essential oil of Litsea
      kostermansii from Taiwan.
AB  - The hydrodistillated leaf essential oil of Litsea kostermansii was analyzed to
      determine its composition and yield. Seventy-three compounds were identified, the
      main components being beta-eudesmol (22.5%), gamma-eudesmol (18.6%), delta
      selinene (8.5%), alpha-eudesmol (6.0%), and gamma-muurolene (4.7%). Oxygenated
      sesquiterpenes (66.2%) and sesquiterpene hydrocarbons (32.8%) were the
      predominant groups of compounds. The leaf oil exhibited excellent antimicrobial
      activities.

PMID- 19768999
TI  - Composition, antioxidant and antimicrobial activities of the essential oil of
      Marrubium deserti.
AB  - The essential oil from aerial part of Marrubium deserti De Noe (Lamiaceae),
      obtained by hydrodistillation was analyzed by gas chromatography (GC) and gas
      chromatography-mass spectrometry (GC-MS), and evaluated for in vitro
      antimicrobial activity. The antioxidant activity was determined using three in
      vitro assays: scavenging effect on DPPH, the ABTS test and the phosphomolybdenum
      method. Thirty-seven compounds were identified in the oil, with germacrene D as
      the major component (45.7%). This oil was characterized by an important
      hydrocarbon fraction (78.1%) and by the predominance of sesquiterpenes (67.4%).
      M. deserti essential oil had no activity on the tested microorganisms
      (Staphylococcus aureus ATCC 25923, Echerichia coli ATCC 25922, Pseudomonas
      aeruginosa ATCC 27853, Candida albicans and Aspergillus flavus). However the oil
      presented an antioxidant activity.

PMID- 19769000
TI  - Anti-Helicobacter pylori activity and essential oil composition of Thymus
      caramanicus from Iran.
AB  - The essential oil of the dried aerial parts of Thymus caramanicus at full
      flowering stage was prepared by hydrodistillation with a yield of 2.5% oil. The
      oil analysis by a combination of capillary GC and GC-MS revealed 26 components of
      which carvacrol (68.9%) was the main component, followed by p-cymene (6.0%),
      thymol (5.3%), gamma-terpinene (4.6%) and borneol (4.0%) representing 98.9% of
      the total oil. The in vitro antibacterial activity of the essential oil was
      determined against ten clinical isolates of Helicobacter pylori using disc
      diffusion, as well as measurement of minimum inhibitory concentrations. The
      results showed high inhibitory activity against all test bacteria by the disc
      diffusion method (zones of inhibition of 50.0 - 65.0 mm). Minimum inhibitory
      concentration values were within the range 14.5 - 58.0 microg/mL for the clinical
      isolates.

PMID- 19769001
TI  - Differential acetyl cholinesterase inhibition by volatile oils from two specimens
      of Marlierea racemosa (Myrtaceae) collected from different areas of the Atlantic
      Rain Forest.
AB  - The volatile oil composition and anti-acetyl cholinesterase activity were
      analyzed in two specimens of Marlierea racemosa growing in different areas of the
      Atlantic Rain Forest (Cananeia and Caraguatatuba, SP, Brazil). Component
      identifications were performed by GC/MS and their acetyl cholinesterase
      inhibitory activity was measured through colorimetric analysis. The major
      constituent in both specimens was spathulenol (25.1% in Cananeia and 31.9% in
      Caraguatatuba). However, the first one also presented monoterpenes (41.2%), while
      in the Carguatatuba plants, this class was not detected. The oils from the plants
      collected in Cananeia were able to inhibit the acetyl cholinesterase activity by
      up to 75%, but for oils from the other locality the maximal inhibition achieved
      was 35%. These results suggested that the monoterpenes are more effective in the
      inhibition of acetyl cholinesterase activity than sesquiterpenes as these
      compounds are present in higher amounts in the M. racemosa plants collected in
      Cananeia.

PMID- 19769002
TI  - Factors affecting chemical variability of essential oils: a review of recent
      developments.
AB  - This review, covering mainly papers of the last decade, focuses on recent
      findings on the different factors affecting the chemical composition of essential
      oils, such as exogenous and endogenous factors. The endogenous factors are
      related to anatomical and physiological characteristics of the plants and to the
      biosynthetic pathways of the volatiles, which might change in either the
      different tissues of the plants or in different seasons, but also could be
      influenced by DNA adaptation. The exogenous factors, over a long period, might
      affect some of the genes responsible for volatiles formation. Those factors lead
      to ecotypes or chemotypes in the same plant species. In the last few years
      chemotaxonomy has been widely used to classify plants with essential oils
      characterized by intra-specific chemical polymorphism. It could be evidenced that
      chemotypes are frequently genotypes and recently the application of the Random
      Amplified Polymorphic DNA (RAPD) markers, coupled with powerful statistical
      methods, appeared to be useful in discriminating the different genotypes. The
      data presented led to the suggestion that further chemotaxonomic studies should
      be the result of the analysis of morphological traits combined both with chemical
      and molecular markers.

PMID- 19769003
TI  - Microbial transformation of sesquiterpenoids.
AB  - Biotransformations are useful methods for producing medicinal and agricultural
      chemicals from both active and inactive natural products with the introduction of
      chemical functions into remote sites of the molecules. Research on microbial
      biotransformations of commonly available sesquiterpenoids into more valuable
      derivatives has always been of interest because of their economical potential to
      the perfume, food, chemical and pharmaceutical industries. Fungal transformations
      of sesquiterpenoids have been less frequently studied compared with many other
      natural products. In recent years, however, much attention has been given to the
      exploitation of new products with enhanced biological activity using
      microorganisms. This review, covering the period from 1990 to 2006, summarizes
      our knowledge of the biotransformations of sesquiterpenoids by various fungi.
      Such transformations could lead to the discovery of new reaction pathways that
      might be useful in the design of new value-added products.

PMID- 19769004
TI  - Race/ethnic and sex differences in large and small artery elasticity--results of
      the multi-ethnic study of atherosclerosis (MESA).
AB  - OBJECTIVE: Reduction in arterial elasticity marks progression toward
      cardiovascular morbidity and mortality. Variability in arterial elasticity may
      help account for race/ethnic and gender differences in cardiovascular risk.
      DESIGN: Cross-sectional study. SETTING: Whites, African Americans, Hispanics and
      Chinese aged 45-84 years free of clinically recognized cardiovascular disease
      were recruited in six US communities. PARTICIPANTS: We examined 3,316 women and
      3,020 men according to race/ethnicity and sex. MAIN OUTCOME MEASURES: Large (LAE)
      and small artery (SAE) elasticity, derived from radial artery diastolic pulse
      wave contour registration in all subjects in a supine position using tonometry.
      LAE and SAE were adjusted for ethnicity, age, clinical site, height, heart rate,
      blood pressure, antihypertensive medication and body mass index, diabetes,
      smoking, and circulating lipids. RESULTS: Much of the sex difference in arterial
      elasticity was explained by height. After adjustment, LAE did not differ by race/
      ethnicity, but mean SAE in African Americans was 4.2 mL/mm Hg x 100 and 4.4 mL/
      mm Hg x 100 in Hispanics compared to means of 4.6 mL/mm Hg x 100 in Whites, and
      4.8 mL/mm Hg x 100 in Chinese. CONCLUSIONS: Reduced SAE may indicate earlier
      vascular disease in African Americans and Hispanics than other groups.

PMID- 19769006
TI  - A preliminary investigation of cognitive appraisal and cardiovascular reactivity
      and recovery in Arab Americans.
AB  - BACKGROUND: Arab Americans exhibit higher rates of hypertension and other
      cardiovascular risk factors relative to national averages. While research
      suggests some minorities may exhibit increased cardiovascular reactivity (CVR)
      to, and slowed recovery from, stress compared to Whites, which may represent a
      risk factor for hypertension and cardiovascular disease, this has not been
      studied in Arab Americans. This study examined differences between Arab Americans
      and Whites in cognitive appraisal, and blood pressure and heart rate (HR)
      reactivity and recovery to laboratory stressors. METHODS: The undergraduate
      sample included 27 Arab Americans (16 female) and 27 gender matched Whites.
      Eligible participants completed two stressful laboratory tasks (mental arithmetic
      [MA] and stress-recall [SR]). Cognitive appraisals were assessed for each task,
      and physiological data were collected during baseline, each laboratory task, and
      recovery. Ethnicity differences in baseline cardiovascular values and cognitive
      appraisals were examined with t-tests, while differences in CVR and recovery were
      tested with ANCOVA, controlling for initial values. RESULTS: Arab Americans
      showed lower baseline systolic blood pressure and mean arterial pressure than
      Whites. Arab Americans also reported greater threat and stress associated with
      MA, and greater threat for SR. No CVR differences were observed during MA;
      however during and after SR, Arab Americans evidenced lesser systolic and
      diastolic blood pressure reactivity and lesser HR recovery compared to Whites.
      CONCLUSIONS: Overall, Arab Americans showed lesser reactivity than Whites, but
      also exhibited slower HR recovery. These results may be attributable to
      physiological habituation to chronic stress associated with minority status.

PMID- 19769007
TI  - On human tissue kallikrein activity in urine of Brazilian White and Black primary
      hypertensive patients.
AB  - OBJECTIVE: To evaluate the possible relationship between the human tissue
      kallikrein amidase activity with sex and ethnicity in Brazilian primary
      hypertensive patients. DESIGN: Population-based study. PARTICIPANTS: One hundred
      men and women, Black and White primary hypertensive patients aged 20 years and
      older were selected. Eighty nine healthy individuals, paired according to age,
      sex, and ethnics were used as controls. METHODS: Early-morning midstream urine
      was used. Human tissue kallikrein amidase activity was estimated with D-Val-Leu
      Arg 4-nitroanilide substrate. Creatinine was determined by a method based on
      Jaffe's reaction. hK1 amidase activity is expressed in microM/(min x mg
      creatinine) to correct for differences in urine flow rate. Data are expressed as
      medians. RESULTS: Human tissue kallikrein amidase activity was significantly
      lower in the urine of hypertensive patients (0.210 microM/(min x mg creatinine)
      than in the urine of control subjects (0.260 microM/(min x mg creatinine) (P =
      .010). This result supports data from the literature. Contrasting to what was
      already reported, namely that human tissue kallikrein excretion is higher in
      females than in males, and especially higher in Caucasians than in African
      Americans, our results show that, in the urine of Brazilian hypertensive patients
      and control subjects, no significant effect of sex and ethnicity on human tissue
      kallikrein amidase activity was observed. CONCLUSIONS: The lack of ethnicity
      effect supports what was already asserted, namely, that, in Brazil, at an
      individual level, color, as determined by physical evaluation, is a poor
      predictor of genomic African ancestry, estimated by molecular markers.

PMID- 19769005
TI  - The association between racial and gender discrimination and body mass index
      among residents living in lower-income housing.
AB  - BACKGROUND: Research on the association between self-reported racial or gender
      discrimination and body mass index (BMI) has been limited and inconclusive to
      date, particularly among lower-income populations. OBJECTIVES: The aim of the
      current study was to examine the association between self-reported racial and
      gender discrimination and BMI among a sample of adult residents living in 12
      urban lower-income housing sites in Boston, Masschusetts (USA). METHODS: Baseline
      survey data were collected among 1,307 (weighted N = 1907) study participants.
      For analyses, linear regression models with a cluster design were conducted using
      SUDAAN and SAS statistical software. RESULTS: Our sample was predominately Black
      (weighted n = 956) and Hispanic (weighted n = 857), and female (weighted n =
      1420), with a mean age of 49.3 (SE: .40) and mean BMI of 30.2 kg m(-2) (SE: .19).
      Nearly 47% of participants reported ever experiencing racial discrimination, and
      24.8% reported ever experiencing gender discrimination. In bivariate and
      multivariable linear regression models, no main effect association was found
      between either racial or gender discrimination and BMI. CONCLUSIONS: While our
      findings suggest that self-reported discrimination is not a key determinant of
      BMI among lower-income housing residents, these results should be considered in
      light of study limitations. Future researchers may want to investigate this
      association among other relevant samples, and other social contextual and
      cultural factors should be explored to understand how they contribute to
      disparities.

PMID- 19769008
TI  - Psychiatric symptom presentation in ethnically diverse cardiology patients.
AB  - OBJECTIVES: The purpose of our study was to examine rates of depression and
      distress among different ethnic groups receiving care in an outpatient cardiology
      clinic. DESIGN: Cross sectional study. SETTING: Participants were recruited from
      an urban cardiology clinic. PARTICIPANTS: Data are presented for 1003 patients
      screened between June 2005 and November 2007. The ethnic groups represented were
      Hispanics (504 patients or 50% of the sample), Southeast Asians (229 patients or
      23%), Caucasians (114 patients or 11%), East Asians (89 patients or 9%), Africans
      (53 patients or 5%), and 14 patients (2%) of unknown or other ethic backgrounds.
      MAIN OUTCOME MEASURES: All patients registered for an outpatient visit received
      questionnaires, in English or Spanish, screening for depression (Patient Health
      Questionnaire [PHQ-9]) and distress (the impact of Events Scale [IES]). RESULTS:
      Overall, significantly more patients screened positive for distress than
      depression (33% vs 27%, X2 = 130.11, P = .00). The ANOVA comparing PHQ scores by
      ethnic group was significant, F(4, 867) = 4.46, P = .01 with Hispanics and
      Southeast Asians scoring significantly higher than East Asians. An ANOVA
      comparing IES scores by ethnic group was also significant, F (4, 760) = 3.63, P =
      .01.with Southeast Asians scoring significantly higher than Caucasians.
      CONCLUSIONS: Elevated levels of psychiatric symptoms are common across ethnic
      groups in medical settings, particularly in patients of Hispanic and Southeast
      Asian origin. Devising culturally sensitive procedures is imperative to
      successful screening and evaluation.

PMID- 19769009
TI  - Trend analysis of diagnosed diabetes prevalence among American Indian/Alaska
      native young adults--United States, 1994-2007.
AB  - OBJECTIVE: In this study, we build on the previous findings of increased diabetes
      prevalence among American Indian/Alaska Native (AI/AN) young adults, by studying
      the rate at which annual prevalence estimates of diagnosed diabetes increased
      from 1994 to 2007. DESIGN AND SETTING: For this study, BRFSS data for 1994-2007
      from the 50 states, District of Columbia, Puerto Rico, Guam, and the Virgin
      Islands were analyzed. PARTICIPANTS: Only non-institutionalized adults aged 18
      years and older were eligible to participate in the Behavioral Risk Factor
      Surveillance System survey. MAIN OUTCOME MEASURES: To examine the existence and
      strength of a trend, we analyzed plots and Spearman's rank correlation
      coefficients of annual prevalence estimates for each group of young adults.
      Mantel-Haenszel tests were employed to study the relationship of diagnosed
      diabetes prevalence and race (AI/ AN, non-Hispanic White), while controlling for
      the time periods 1994-2000 and 2001-2007. To quantify increases in the disparity
      of diagnosed diabetes prevalence and race (AI/ AN, non-Hispanic White), odds risk
      ratio estimates were employed to approximate corresponding prevalence ratio
      estimates for the time periods 1994-2000 and 2001-2007. RESULTS: Employing
      Spearman's test for trend resulted in observing, during 1994-2007, statistically
      significant increasing trends in the annual prevalence estimates of diagnosed
      diabetes among AI/AN and non-Hispanic White young adults. AI/AN young adults, on
      average, were 1.7 (95% CI; [1.12, 2.63]) times more likely than non-Hispanic
      White young adults to be diagnosed with diabetes during 1994-2000 and 2.5 (95%
      CI; [1.93, 3.32]) times more likely during 2001-2007. CONCLUSION: The findings in
      this study suggests that the disparity in the estimated prevalence of diagnosed
      diabetes between AI/AN and NHW young adults widened steadily from 2001 to 2007.

PMID- 19769010
TI  - Sociodemographic and healthcare characteristics of Colonia residents: the role of
      life stage in predicting health risks and diabetes status in a disadvantaged
      Hispanic population.
AB  - An assessment of the risk or diagnosis of diabetes in a random sample of 386
      adult border residents found 46% obese, 12% at risk for diabetes, and 18%
      diagnosed with diabetes. While obesity was associated with greater diabetes risk,
      > 50% of obese adults reported not being told of their diabetes risk. Independent
      of other characteristics, boomers were at increased risk (OR 3.88) for diabetes.
      Comorbidities increased the risk for actual diabetes diagnosis (OR 4.79).
      Skipping medications increased risk of developing diabetes (OR 2.98).
      Disadvantaged obese boomers are at particular risk, warranting culturally
      appropriate interventions before onset of chronic illnesses.

PMID- 19769011
TI  - Disparities in the prevalence of diabetes: is it race/ethnicity or socioeconomic
      status? Results from the Boston Area Community Health (BACH) survey.
AB  - OBJECTIVES: Many researchers and clinicians continue to believe that non
      modifiable race/ ethnicity is a major contributor to diabetes, prompting a well
      intentioned search for genetic and bio-physiological explanations. We seek to
      reinforce earlier findings showing that socioeconomic status is more strongly
      associated with diabetes prevalence than race/ ethnicity and suggests a very
      different and potentially modifiable etiologic pathway. METHODS: A community
      based epidemiologic survey of 5503 Boston residents aged 30-79 years (1767 Black,
      1877 Hispanic, 1859 White; 2301 men and 3202 women). RESULTS: After adjusting for
      age and sex, Blacks and Hispanics have statistically significantly increased odds
      of having diabetes: Black (OR, 2.0; 95% CI, 1.4-2.9) and Hispanic (2.4; CI 1.6
      3.4) compared to Whites. If socioeconomic status, a combination of education and
      income, is added to the model, these odds are reduced for both Blacks (OR 1.6;
      CI, 1.1-2.2) and Hispanics (OR 1.6; CI, 1.1-2.3). In a multivariate logistic
      regression adjusting for age, sex, socioeconomic status, obesity, hypertension,
      gestational diabetes, physical activity, trouble paying for basics, health
      insurance status, and family history of diabetes, these odds are reduced further:
      Black (OR 1.0; CI, 0.7-1.5) and Hispanic (OR 1.3; CI, 0.9-2.1) and are no longer
      statistically significant. CONCLUSIONS: Consistent with other reports, we find
      socioeconomic status has a much stronger association with diabetes prevalence
      than race/ethnicity. Continuing to focus on race/ethnicity as a primary
      determinant of diabetes prevalence overemphasizes the importance of biomedical
      factors and diverts effort from socio-medical interventions such as improving
      social circumstances, access to effective care, and upstream redistributive
      social policies.

PMID- 19769012
TI  - The prevalence of self-reported chronic conditions among Arab, Chaldean, and
      African Americans in southeast Michigan.
AB  - OBJECTIVES: While there is a plethora of research on the prevalence of individual
      chronic conditions, studies that examine the clustering of these conditions are
      lacking, especially among immigrant, minority groups. DESIGN: Cross-sectional,
      convenience sample. SETTING: A self-administered survey was distributed at
      churches, mosques, and small businesses. PARTICIPANTS: Arabs (n = 1383),
      Chaldeans (n = 868), Blacks (n = 809) and Whites (n = 220) in southeast Michigan.
      MAIN OUTCOME MEASURES: We estimated the prevalence of hypertension, high
      cholesterol, heart disease, diabetes, asthma, and depression. Using a logistic
      regression model, we estimated odds ratios and 95% confidence intervals for the
      association between ethnicity and reporting one or more chronic conditions before
      and after adjusting for demographic, socioeconomic status, health care, chronic
      conditions, and health behavior variables. RESULTS: The overall age and sex
      adjusted prevalence of having one or more chronic conditions was 44%. Estimates
      were lower for Chaldeans (32%) compared to Arabs (44%), Whites and Blacks (50%
      for each group). In the fully adjusted model, Chaldeans were less likely (OR =
      0.62; 95% CI = 0.43-0.89) to report having one more chronic conditions compared
      to Whites. CONCLUSIONS: Future studies should employ probability samples, and
      should collect more detailed sociodemographic and acculturation data, which
      influence the relationship between race/ethnicity and the prevalence of chronic
      conditions.

PMID- 19769013
TI  - The impact of race and ethnicity on disease severity in systemic lupus
      erythematosus.
AB  - OBJECTIVES: Systemic lupus erythematosus (SLE) can result in comorbidities and
      high disease severity. The aim of this study was to evaluate the effects of age,
      sex, race, ethnicity, cost of hospitalization, length of stay, and payor source
      on SLE disease severity scores. DESIGN: Epidemiological study. SETTING: Hospital
      discharge data were obtained from the DFW Hospital Council (DFWHC), for 65,535
      patients hospitalized in the North Texas Dallas-Fort Worth (DFW) Metropolitan
      Statistical Area (MSA) from 1999-2005 with at least one autoimmune disease.
      PATIENTS: Of the 65,535 autoimmune patients, 14,829 patients had SLE as a
      diagnosis. The sample was assessed for disease severity according to the SLE
      comorbidity Index. MAIN OUTCOME: Disease severity, SLE comorbidities. RESULTS:
      SLE patients were younger and more than five times more likely to have multiple
      autoimmune diseases. More than one third of Hispanic patients were on Medicaid or
      self-pay and more likely to have higher disease severity. Race (Caucasian), sex
      (female), and payor source (PPO/POS) predicted lower disease severity scores. SLE
      was predictive of eight of the fourteen SLE-CI diseases, with greatest effects
      observed for nephritis (OR = 3.30, P < .0001), chronic renal failure (OR = 3.36,
      P < .0001), pericarditis (OR = 3.2, P < .0001), and pleuritis (OR = 2.06, P <
      .0001). Non-Caucasian patients were more likely to have chronic renal failure,
      nephritis, congestive heart failure, pericarditis and pleuritis. CONCLUSIONS: The
      comorbidities that exist in SLE vary according to ethnicity. It is paramount for
      physicians to be cognizant of these disparities and make appropriate referrals.

PMID- 19769014
TI  - Associations of chronic obstructive pulmonary disease with all-cause mortality in
      Blacks and Whites: the atherosclerosis risk in communities (ARIC) study.
AB  - OBJECTIVE: To determine the burden of chronic obstructive pulmonary disease
      (COPD) on all-cause mortality in Blacks and Whites from four US communities.
      METHODS: We determined prospectively the risk of death through December 2004 in
      relation to baseline (1987-1989) COPD status in 10,333 Black and White
      participants of the Atherosclerosis Risk in Communities (ARIC) study. RESULTS:
      Over a mean follow-up of 15 years (maximum 18 years), 462 deaths occurred in
      Blacks and 1221 deaths occurred in Whites. Hazard ratios for all-cause mortality
      among Blacks and Whites were similar (hazard ratio [HR] = 1.74 in Blacks and HR =
      1.59 in Whites), indicating a 59%-74% greater risk of mortality for those with
      COPD. However, for both those with and without COPD, crude death rates were
      approximately double in Blacks compared to Whites. CONCLUSIONS: Our findings
      suggest that given COPD, Blacks and Whites have the same proportionate increase
      in mortality and that the difference in death rates between Blacks and Whites
      cannot be explained by COPD status. The public health burden of COPD is enormous,
      and strategies to reduce COPD and smoking could have a large impact on total
      mortality rates of both Blacks and Whites.

PMID- 19769015
TI  - Colorectal cancer test use among Californians of Mexican origin: influence of
      language barriers.
AB  - OBJECTIVES: Striking decreases in colorectal cancer (CRC) incidence have been
      seen recently in non-Latino Whites but not in Latinos. The purpose of our study
      was to examine the influence of limited English proficiency (LEP) on differences
      in CRC test use rates between Mexican American and non-Latino White adults in
      California and reported reasons for not getting a CRC exam. DESIGN: Cross
      sectional analysis of the 2005 California Health Interview Survey (CHIS).
      SETTING: Representative sample of non-institutionalized adults living in
      California. PARTICIPANTS: Mexican American (n = 1,529) and non-Latino White men
      and women aged 50 and older (n = 16,775) who had not been diagnosed with CRC.
      ANALYSIS: Logistic regression analyzed the effect of ethnicity and limited
      English proficiency (LEP) on CRC test use after adjusting for sociodemographics,
      healthcare access, health status, and other health behaviors. MAIN OUTCOME
      MEASURES: Respondents' likelihood of not receiving the CRC exam was examined as a
      function of ethnicity and LEP status; differences in reasons for not receivingCRC
      testing between ethnic groups were also examined. RESULTS: More than 40% of
      Californian Mexican American adults aged 50 and older have never had either fecal
      occult blood test or lower endoscopy CRC tests. Mexican Americans were more
      likely to have difficulty understanding their doctor due to language barriers (P
      < .01). Mexican Americans more often reported provider barriers in getting an
      endoscopy (ie, test was not recommended by their medical provider) than non
      Latino Whites (P = .01). After adjustment for covariates, Mexican Americans were
      1.32 times and those with LEP were 1.68 times more likely to have never had
      either CRC test. CONCLUSIONS: Limited English proficiency significantly decreased
      the likelihood of getting tested for CRC (P < .01). Eliminating language barriers
      should result in improvements in CRC test use among limited English proficiency
      Mexican Americans.

PMID- 19769016
TI  - Sociodemographic correlates of stage of adoption for colorectal cancer screening
      in African Americans.
AB  - OBJECTIVES: African Americans have the highest incidence and mortality rates from
      colorectal cancer in the United States. Endoscopic screening, while effective in
      reducing both, is greatly underutilized. This research sought to understand
      sociodemographic factors related to stage of readiness for endoscopic screening.
      DESIGN: One hundred fifty nine African American women (76.1%) and men (mean age =
      57.0 years) who were non-adherent to endoscopic screening guidelines were
      recruited and asked to complete semi-structured interviews. SETTING: Participants
      were all being seen for a non-acute primary care medical visit at one of two
      urban hospitals. The theoretical framework that informed this study was the Trans
      theoretical Model (TTM) and the emphasis on Stage of Change or intention for
      undergoing endoscopic screening. MAIN OUTCOME AND MEASURES: Based on their stage
      of readiness to undergo screening, 67 (42%) were categorized as precontemplative
      (Has no plans to have a colonoscopy) while 92 were categoriezed as being in a
      contemplative or preparation stage. Using chi-square and Student t-tests,
      differences were examined between the two groups. RESULTS: No sociodemographic
      variables distinguished the two groups. However, people in the
      contemplative/preparation group were more likely to: have a regularly seen
      healthcare professional (63.7% vs 36.3%; P = .005), have had a previous
      recommendation for screening (65.7% vs 34.3%; P = .003); had heard of a
      colonoscopy (63.6% vs 36.4%; P = .000) and have been told by a healthcare
      professional that they needed a colonoscopy (73.1% vs 26.9%; P = .000).
      CONCLUSIONS: This study helps us to better understand the relevance of
      sociodemographic characteristics that may be associated with completing
      endoscopic colorectal cancer screening. In addition, we confirm that physician
      recommendation and individual awareness of the procedure are significant factors
      in readiness to get screened.

PMID- 19769017
TI  - The association between perceived provider discrimination, healthcare utilization
      and health status in racial and ethnic minorities.
AB  - BACKGROUND AND OBJECTIVES: A commonly cited explanation of how racial
      discrimination impacts health is the biopsychosocial model. However, the
      biopsychosocial model does not allow for the effects of perceived provider
      discrimination on health behavior and utilization. In fact, researchers have
      directed relatively little attention toward the direct and indirect effects of
      perceived provider discrimination on both healthcare utilization and health
      status. We, therefore, compared the extent to which perceived provider
      discrimination explains racial/ethnic differences in healthcare utilization and
      subsequently health status. METHODS: The data came from the 2001 Survey on
      Disparities in Quality of Health Care. The final analytic sample was 5,642 adults
      living in the US. Structural equation modeling evaluated the relationship between
      perceived provider discrimination, healthcare utilization, and health status.
      RESULTS: African Americans, Hispanics and Asians reported significantly more
      perceived provider discrimination and poorer health compared to non-Hispanic
      whites. Poor health is significantly mediated by two paths: (1) by perceived
      provider discrimination and (2) by perceived provider discrimination through
      unmet need for healthcare utilization. CONCLUSIONS: Perceived provider
      discrimination contributes to health disparities in African Americans, Hispanics
      and Asians. Perceived provider discrimination has a direct effect on self
      reported health status. Additionally, because minorities perceive more provider
      discrimination, they are more likely to delay health seeking. In turn, this delay
      is associated with poor health. This enriches our understanding of how
      racial/ethnic health disparities are created and sustained and provides a
      concrete mechanism on how to reduce health disparities.

PMID- 19769018
TI  - Multidimensional health locus of control in American Indians: the strong heart
      study.
AB  - OBJECTIVE: Observe and record the demographic and anthropomorphic correlates of
      health beliefs in American Indians using the multidimensional health locus of
      control (MHLC) scale. DESIGN: Self-administration or interview rating of Form B
      of the MHLC scale. SETTING: Arizona, Oklahoma, and Dakota branches of The Strong
      Heart Study PARTICIPANTS: 3665 participants (1468 men and 2197 women) aged 15 to
      93 years (average 39.9) of Phase IV of The Strong Heart Study. MAIN OUTCOME
      MEASURES: MHLC subscale scores, demographics, anthropometrics RESULTS: 
      DEMOGRAPHICS: Women had higher Chance health locus of control (HLC) than men, but
      otherwise similar MHLC scores. Age positively correlated with lower Internal HLC
      and higher Powerful Others HLC. Education was associated with lower Chance HLC.
      MHLC scores differed by center (AZ, OK, and SD). Anthropometrics: Men with high
      body fat or high waist-to-hip ratio had higher Powerful Others HLC. Waist-to-hip
      ratio in women positively correlated to Powerful Others HLC and Chance HLC. BMI
      was not a strong indicator of differences in MHLC. CONCLUSIONS: To our knowledge,
      this is the first study to examine health locus of control in American Indians.
      The health beliefs of American Indians in this study were similar to previous
      demographic studies in other populations. The associations between certain health
      beliefs and obesity deserve further exploration to gauge prospective risk.
      Clinicians should continue to identify psychological issues and counsel American
      Indian patients in culturally sensitive ways for improved preventive care
      delivery and increased efficacy of health education.

PMID- 19769019
TI  - Patient-physician race concordance and its relationship to perceived health
      outcomes.
AB  - OBJECTIVES: Race concordance occurs when the race of a patient matches the race
      of his/ her physician and discordance occurs when races do not match. Previous
      research has suggested an association between race concordance and measures of
      patient satisfaction and health outcome. In this study, we examined the
      relationship between race concordance and perceived quality of care, self
      reported general health, and the SF-12 measures of physical and mental health in
      a community-based sample of 2001 adults. DESIGN: Telephone interviews were
      conducted with randomly selected households sampled from commercial lists of
      phone numbers. ANALYSIS: The association of concordance with the outcomes was
      analyzed separately for African American (n = 1,125) and White (n = 876)
      respondents using bivariate analysis and multiple linear regression. RESULTS:
      After controlling for age, sex, income, education, insurance status, and type of
      insurance, we found that race concordance was only associated with general health
      for White respondents (P < .006). Whites with insurance were more likely to be
      concordant than Whites without insurance and African Americans without insurance
      were more likely to be concordant than African Americans with insurance.
      CONCLUSIONS: Settings that employ a larger number of African American physicians
      in Nashville, Tennessee are places that people without insurance are more likely
      to seek health care. For health satisfaction and perceived health status,
      socioeconomic status and access to quality health care are likely more important
      than whether one's physician is of a similar or dissimilar race.

PMID- 19769020
TI  - Use of focus groups in multi-site, multi-ethnic research projects for women's
      health: a Study of Women Across the Nation (swan) example.
AB  - OBJECTIVE: To outline the lessons learned about the use of focus groups for the
      multisite, multi-ethnic longitudinal Study of Women Across the Nation (SWAN).
      Focus groups were designed to identify potential cultural differences in the
      incidence of symptoms and the meaning of transmenopause among women of diverse
      cultures, and to identify effective recruitment and retention strategies. DESIGN:
      Inductive and deductive focus groups for a multi-ethnic study. SETTING: Seven
      community research sites across the United States conducted focus groups with six
      ethnic populations: African American, Chinese American, Japanese American,
      Mexican American, non-Hispanic white, and Puerto Rican. PATIENTS OR PARTICIPANTS:
      Community women from each ethnic group of color. INTERVENTIONS: A set of
      four/five focus groups in each ethnic group as the formative stage of the
      deductive, quantitative SWAN survey. MAIN OUTCOME MEASURES: Identification of
      methodological advantages and challenges to the successful implementation of
      formative focus groups in a multi-ethnic, multi-site population-based
      epidemiologic study. RESULTS: We provide recommendations from our lessons learned
      to improve the use of focus groups in future studies with multi-ethnic
      populations. CONCLUSIONS: Mixed methods using inductive and deductive approaches
      require the scientific integrity of both research paradigms. Adequate resources
      and time must be budgeted as essential parts of the overall strategy from the
      outset of study. Inductive cross-cultural researchers should be key team members,
      beginning with inception through each subsequent design phase to increase the
      scientific validity, generalizability, and comparability of the results across
      diverse ethnic groups, to assure the relevance, validity and applicability of the
      findings to the multicultural population of focus.

PMID- 19769021
TI  - Geriatric admissions in a developing country: experience from a tertiary centre
      in Nigeria.
AB  - BACKGROUND: The aging populations in developing countries have brought a
      demographic and an epidemiological transition, affecting the impact of chronic
      diseases on the health status of the population. OBJECTIVE: To review the pattern
      of geriatric admissions in the medical wards of the University of Port Harcourt
      Teaching Hospital (UPTH). METHOD: Medical records of all geriatric patients aged
      > or = 60 years admitted in the medical wards between June 2002 and May 2006 were
      retrieved and reviewed retrospectively. RESULTS: 2736 admissions to the adult
      medical wards over the period were reported. Among these, 1122 (41%) were
      geriatric patients aged > or = 60 years. The most common geriatric illnesses were
      cardiovascular diseases, 622 (43.7%), infections, 268 (18.8%) and endocrine
      diseases, 220 (15.4%). Malignancies, renal diseases and hematological diseases
      were few, being responsible for 53 (3.7%) 48 (3.4%) and 35 (2.5%) of medical
      admissions respectively. Only 1.5% of the patients spent more than 30 days in the
      hospital. More than half (56.4%) of the patients spent 1-2 weeks, while 33.3% of
      patients spent less than a week in hospital. Of the total geriatric patients
      seen, 70.6% recovered and were discharged home, 26.7% died and 2.5% left against
      medical advice. CONCLUSION: Elderly patients constitute a high proportion of in
      patient medical admissions. Chronic diseases were responsible for the majority of
      morbidity and mortality in the elderly patients.

PMID- 19769022
TI  - For the patient. Elasticity of small arteries in African Americans is lower than
      that found in Caucasians.

PMID- 19769023
TI  - How stressful events affect Arab Americans heart health.

PMID- 19769024
TI  - For the patient. Systemic lupus erythematosus more severe in non-Caucasians and
      Hispanics.

PMID- 19769025
TI  - Review of American fossil Phlebotominae (Diptera: Psychodidae) with a description
      of two new species.
AB  - The objective of this study was to carry out a taxonomic review of fossil
      American phlebotomine sand flies and describe two new species found in amber in
      the Dominican Republic. The gonostyle of one of these, Micropygomyia
      dorafeliciangeliae nov. sp., (= Lutzomyia dorafeliciangeliae, species group
      oswaldoi), has five spines, similar to that of Micropygomyia paterna (Quate,
      1963) (= Lutzomyia paterna, species group oswaldoi), but they may be
      distinguished by the alpha/gamma ratio, which is < 1.0 in the new species and > 1
      in the latter. Pintomyia dominicana nov. sp. (= Lutzomyia dominicana, species
      group verrucarum) has four spines on the gonostyle and presents a long bristle on
      the apex of the paramere, which distinguishes it from the other fossil species.
      With the description of these two new species, a total of 14 species of the
      American fossil phlebotomine sand flies has been described, 10 of which belong to
      the genus Pintomyia. An identification key for male fossil species is presented.

PMID- 19769026
TI  - Scanning electron microscopy of the egg of Ochlerotatus albifasciatus (Diptera:
      Culicidae).
AB  - Ochlerotatus albifasciatus (Macquart) (Diptera: Culicidae) is a mosquito species
      of medical and veterinary importance, usually associated with temporary
      groundwater habitats. Eggs obtained from females collected in Cordoba city, in
      the center of Argentina, were studied using scanning electron microscopy. The
      eggs are elliptical in outline, measuring approximately 615.7 +/- 37.24 microm in
      length (1) and 180.7 +/- 22.87 microm in width (w), with an egg index (l/w ratio)
      of 2.9-3.7. The outer chorionic sculpture has racquet-shaped and wristwatch
      shaped cells consisting of a small central tubercle surrounded by larger
      tubercles and followed by a row of smaller tubercles on one or both sides,
      respectively, although variations between regions of the egg were observed. The
      micropylar apparatus has a collar with evident molding and edges of determined
      length, albeit irregular, with defined margins for the transition area and a
      thickness of approximately 10.7 microm. The margins of the micropylar disc are
      raised and the disc measures approximately 21.1 microm in diameter. The micropyle
      is distinct.

PMID- 19769027
TI  - Two new species of Sarcophaga s. lat. from Thailand with a key to species
      (Diptera: Sarcophagidae).
AB  - During a distribution survey of flies of medical importance around northern
      Thailand, we discovered two new species of flesh fly Sarcophaga (s. lat.)
      (Diptera: Sarcophagidae) that also are new to science. The species are Sarcophaga
      nanensis sp. nov. and Sarcophaga kiyokoae sp. nov. Adults of the former species
      was recovered from Pua River of Nan province (19 degrees 12'29" N, 100 degrees
      56' 36" E) 442 m in northern Thailand, whereas the latter species was collected
      around Kuang River (19 degrees 0'3" N, 99 degrees 17'16" E) 551 m of the lowland
      forests of Chiang Mai province, northern Thailand. Although these two sarcophagid
      flies showed similarity in their male terminalia in having large aedeagi and
      rounded juxta, illustrations of the sternite 5, cercus, surstylus, and
      anterolateral margin of the aedeagus allow differentiation between them. A key is
      provided to the adult males of the flesh flies of medical importance in Thailand.

PMID- 19769029
TI  - Temporal distribution of Aedes aegypti in different districts of Rio de Janeiro,
      Brazil, measured by two types of traps.
AB  - Dengue dynamics in Rio de Janeiro, Brazil, as in many dengue-endemic regions of
      the world, is seasonal, with peaks during the wet-hot months. This temporal
      pattern is generally attributed to the dynamics of its mosquito vector Aedes
      aegypti (L.). The objectives of this study were to characterize the temporal
      pattern of Ae. aegypti population dynamics in three neighborhoods of Rio de
      Janeiro and its association with local meteorological variables; and to compare
      positivity and density indices obtained with ovitraps and MosquiTraps. The three
      neighborhoods are distinct in vegetation coverage, sanitation, water supply, and
      urbanization. Mosquito sampling was carried out weekly, from September 2006 to
      March 2008, a period during which large dengue epidemics occurred in the city.
      Our results show peaks of oviposition in early summer 2007 and late summer 2008,
      detected by both traps. The ovitrap provided a more sensitive index than
      MosquiTrap. The MosquiTrap detection threshold showed high variation among areas,
      corresponding to a mean egg density of approximately 25-52 eggs per ovitrap. Both
      temperature and rainfall were significantly related to Ae. aegypti indices at a
      short (1 wk) time lag. Our results suggest that mean weekly temperature above 22
      24 degrees C is strongly associated with high Ae. aegypti abundance and
      consequently with an increased risk of dengue transmission. Understanding the
      effects of meteorological variables on Ae. aegypti population dynamics will help
      to target control measures at the times when vector populations are greatest,
      contributing to the development of climate-based control and surveillance
      measures for dengue fever in a hyperendemic area.

PMID- 19769028
TI  - Temporal variations of wing size and shape of Triatoma infestans (Hemiptera:
      Reduviidae) populations from northwestern Argentina using geometric morphometry.
AB  - Wing geometric morphometry of Triatoma infestans (Klug) (Hemiptera: Reduviidae)
      populations in northwestern Argentina showed that individual collection sites
      represent the discrete unit where metric differentiation took place. Here we
      studied temporal variations in wing size and shape of T. infestans populations
      from defined capture sites on three occasions between 2000 and 2003. Bugs
      collected from domiciles and/or storerooms had significantly larger right-wing
      centroid size than bugs collected at goat and/or pig corrals by the end of summer
      2000 for both sexes. Conversely, male bugs collected from domiciles and/or
      storerooms had significantly smaller centroid size than bugs collected from pig
      corrals in spring 2002. The inversion in wing centroid size between seasons was
      consistent between sexes. Wing shape analysis from the south-central extreme of
      the study village showed divergence between collection dates for both sexes. Wing
      shape divergence was highly significant between male bugs collected by the end of
      summer 2000 and those collected in spring 2002 and by the end of summer 2003. For
      females, wing shape divergence was marginally significant between the end of
      summer 2000 and spring 2002, and significant between spring 2002 and the end of
      summer 2003. Unlike season-related variations in wing centroid size, shape
      differentiation was related to the time period elapsed between sample collections
      and suggested genetic influences acting on shape. Simultaneous consideration of
      wing size and shape provided complementary information on the direction and
      timing of bug dispersal. Morphological studies may allow determining the degree
      of relatedness of different bug populations and to associate morphological
      heterogeneity with temporal patterns of reinfestation.

PMID- 19769030
TI  - Effect of population structure and size on aggregation behavior of Cimex
      lectularius (Hemiptera: Cimicidae).
AB  - The bed bug, Cimex lectularius L. (Hemiptera: Cimicidae), occurs in aggregations
      until the conditions are no longer beneficial, leading to dispersal. Active and
      passive bed bug dispersal causes migrations from main aggregations either within
      a room, from room to room within a building, or from building to building.
      Because bed bug movement is an important factor in the spread of infestations, we
      wanted to determine how population structure and size affect bed bug
      aggregations. Engorged bed bugs were placed in glass petri dish arenas at varying
      densities, sex ratios, and population compositions. Nymphs had a high tendency to
      aggregate, varying between 94 and 98%, and therefore were not the likely
      dispersal stage of the bed bug. At densities of 10 and 40 adults at a 1:1 sex
      ratio, there were significantly more lone females than lone males. When the
      population composition was varied, the percentage of lone females was
      significantly higher than that of males and nymphs at population compositions of
      40 and 80% adults. When the sex ratio of adults was varied, there were
      significantly more lone females than males in arenas with 20, 50, and 80% males.
      Females, being found away from aggregations significantly more often than any
      other life stage, are potentially the dispersal stage of the bed bug. Active
      female dispersal away from main aggregations can potentially lead to treatment
      failures and should be taken into account when using control methods.

PMID- 19769031
TI  - Temporal dynamics of flight muscle development in Triatoma infestans (Hemiptera:
      Reduviidae).
AB  - Triatoma infestans Klug is dimorphic for flight muscles. This dimorphism may
      affect flight dispersal, reinfestation patterns, and transmission risk. To
      understand the contributions of genes and environment to morph determination, it
      is first necessary to characterize the temporal dynamics of flight muscle
      development. Field-collected T. infestans adults were dissected 20 or 100 d after
      collection, and those collected as nymphs were dissected at approximately 4, 15,
      or 44 d after the imaginal molt. The occurrence of flight muscles was
      additionally assessed by minimally invasive, repeated observations through the
      scutum of live bugs. Overall, 33.5% of 179 males and 7.8% of 179 females had no
      flight muscles. Neither dissections nor repeated observations evidenced changes
      in morph type during adult life, suggesting that the occurrence of flight muscles
      is mostly irreversible within the time span of observations and is determined
      before or during final ecdysis. Flight muscles were detectable at 4 d after
      emergence and achieved complete development within 4-15 d after emergence. The
      repeated observation of thoracic contents through the scutum showed very high
      sensitivity and specificity and apparently had minor effects on mortality. In
      another bug population located 360 km away, 16.4% of 177 males and 6.7% of 149
      females had no flight muscles. Current results show that the sex-biased flight
      muscle dimorphism is a regionally widespread character in T. infestans. This
      character should be considered in field population studies that seek to measure
      reinfestation risk and dispersal in T. infestans and other Triatominae.

PMID- 19769032
TI  - Precipitation and temperature as predictors of the local abundance of Ixodes
      scapularis (Acari: Ixodidae) nymphs.
AB  - Populations of Ixodes scapularis Say nymphs were surveyed at a Lyme disease-
      endemic area for 8 consecutive yr (1998-2005) to characterize annual changes in
      abundance. Precipitation and temperature were also monitored over the period 1998
      2004 to determine their potential value as predictors of tick abundance. Although
      both parameters showed annual variation, no statistical differences in the annual
      abundance of I. scapularis nymphs were observed over the 8-yr period. Our results
      suggest that precipitation and temperature were not predictive of the abundance
      of I. scapularis nymphs.

PMID- 19769033
TI  - Influence of prescribed burns on the abundance of Amblyomma americanum (Acari:
      Ixodidae) in the Missouri Ozarks.
AB  - The increasingly widespread use of prescribed burns to manage oak (Quercus spp.)
      hickory (Carya spp.) forests in the Missouri Ozarks, USA, has considerable
      potential to alter the abundance of Amblyomma americanum (L.) (Acari: Ixodidae),
      the lone star tick, an important vector of several emerging pathogens. In
      particular, responses of important tick hosts, primarily white-tailed deer
      (Odocoileus virginianus), to fire management and the resultant changes in the
      distribution and abundance of A. americanum are largely unknown. Using several
      large burn units (61-242 ha) within the Ozark ecosystem, I measured the effect of
      the time elapsed since sites were burned on the density of white-tailed deer and
      the larval life stage of A. americanum. Larval tick densities were highest in
      areas that were 2 yr postburn and were > 6 times higher than tick densities in
      control units. Deer densities were highest in sites that were burned in the same
      year as this study and decreased significantly with time since burn. These
      results suggest that intensive use of postburn sites by white-tailed deer may
      increase the abundance of A. americanum to levels greater than occurs in sites
      that remain unburned. Thus, fire management, although beneficial in many aspects
      of ecosystem management, may bear the unintended cost of locally increasing
      abundance of A. americanum.

PMID- 19769034
TI  - Experimental assessment of the impacts of northern long-eared bats on ovipositing
      Culex (Diptera: Culicidae) mosquitoes.
AB  - The importance of predation as a mortality factor in adult mosquitoes has
      received only limited attention in the scientific literature. Despite the lack of
      consensus among researchers as to whether bats are important predators of
      mosquitoes, there have been no attempts to directly document the effect of bats
      on mosquito populations or behavior. We conducted an enclosure experiment to test
      the hypothesis that bats reduce the local abundance of ovipositing female
      mosquitoes by examining whether the northern long-eared bat (Myotis
      septentrionalis Trouessart) had an effect on Culex spp. (Diptera: Culicidae)
      oviposition, using naturally occurring mosquitoes, either through direct
      predation or trait mediated effects on mosquito behavior. We found a significant,
      32% reduction in egg-laying activity associated with bat predation. Artificial
      oviposition habitats directly outside bat enclosures experienced no reduction in
      oviposition; we attributed the observed reduction in egg-laying activity to
      direct predation on ovipositing females by bats and not changes in mosquito
      behavior. In addition, we noted a decrease in the number of larval mosquitoes in
      enclosures exposed to bat predation. These results suggest the impact of aerial
      predators on pathogen transmission may be large, and warrants further scientific
      investigation.

PMID- 19769035
TI  - Bionomics of Anopheles minimus and An. fluviatilis (Diptera: Culicidae) in east
      central India, endemic for falciparum malaria: human landing rates, host feeding,
      and parity.
AB  - The host feeding of Anopheles minimus Theobald and An. fluviatilis James was
      studied in the villages of east-central India by conducting human landing
      collections between 1800 and 0600 hours at monthly intervals from May 2006 to
      July 2007. Four species of anopheline mosquitoes, An. minimus, An. fluviatilis,
      An. maculatus Theobald, and An. subpictus Grassi, were collected, the former two
      known vector species of malaria being the most abundant (97.1%). The An. minimus
      complex has been identified as sibling species A and An. fluviatilis complex as
      species S (90.9%) and T (9.1%). Both the species were prevalent throughout the
      year and obtained from landing collections indoors and outdoors. The average
      human landing density (HLD) of An. minimus and An. fluviatilis was 1.76 and 1.78
      indoors and 1.71 and 1.56 per human per night outdoors, respectively. The HLD was
      relatively higher during the rainy season, although not significant in the case
      of An. fluviatilis. The human landing activity of An. minimus and An. fluviatilis
      occurred between 2000 and 0400 hours and peaked during 2300-0200 hours both
      indoors and outdoors.

PMID- 19769036
TI  - Lutzomyia spp. (Diptera: Psychodidae) response to olfactory attractant- and light
      emitting diode-modified Mosquito Magnet X (MM-X) traps.
AB  - Mosquito Magnet-X traps were modified for use with blue, green, red, and blue
      green-red light-emitting diodes and olfactory attractants to determine the
      response of Lutzomyia shannoni (Dyar) and Lutzomyia vexator (Coquillett)
      (Diptera: Psychodidae) field populations to these attractants. Red and blue-green
      red-baited traps captured the highest numbers of Lu. shannoni and Lu. vexator,
      respectively, although, there were no significant differences between the colors.
      Baiting the traps with CO, attracted significantly higher numbers of Lu. shannoni
      but showed no effect on Lu. vexator capture. In comparison with CO, alone, Lu.
      shannoni preferred 1-octen-3-ol and 1-hexen-3-ol (0.05 g per trap) in combination
      with CO.

PMID- 19769037
TI  - Attraction of Triatoma dimidiata and Rhodnius prolixus (Hemiptera: Reduviidae) to
      combinations of host cues tested at two distances.
AB  - The "kissing bugs," Triatoma dimidiata (Latreille) and Rhodnius prolixus (Stal)
      (Reduviidae: Triatominae) are major vectors of Chagas disease in Central and
      South America. To further uncover the attraction to certain host cues by these
      vectors at long and short distances from their host, the behavioral responses of
      two life stages (fifth-instar nymphs and adult males) of these two species to
      different known or suspected attractants, alone or in combination, were
      investigated. Tests were done using short- and long-range environments, namely, a
      four-port olfactometer and a long-range artificial chamber designed to mimic the
      insect's natural habitats. In single-attractant trials, heat alone and CO2 alone
      were found to be more attractive than selected chemicals. In multiple-attractant
      trials, both species and life stages were attracted at short distances, and a
      statistically significant synergistic increase in attraction was observed in long
      distance multimodal tests. Lures containing CO2 were the most effective
      attractants at both long and short distances. R. prolixus adult males were
      significantly less attracted to several lure combinations than the nymphs of
      either species, perhaps because adults were more motivated to seek mates than
      feed. Our findings suggest that although the triatomine bugs may be capable of
      detecting odorants and heat sources at short distances, their ability to locate a
      host over a long distance is best aided by the presence of a CO2 plume.

PMID- 19769038
TI  - Genetic structure of Aedes aegypti in Australia and Vietnam revealed by
      microsatellite and exon primed intron crossing markers suggests feasibility of
      local control options.
AB  - The distribution of Aedes aegypti (L.) in Australia is currently restricted to
      northern Queensland, but it has been more extensive in the past. In this study,
      we evaluate the genetic structure of Ae. aegypti populations in Australia and
      Vietnam and consider genetic differentiation between mosquitoes from these areas
      and those from a population in Thailand. Six microsatellites and two exon primed
      intron crossing markers were used to assess isolation by distance across all
      populations and also within the Australian sample. Investigations of founder
      effects, amount of molecular variation between and within regions and comparison
      of F(ST) values among Australian and Vietnamese populations were made to assess
      the scale of movement ofAe. aegypti. Genetic control methods are under
      development for mosquito vector populations including the dengue vector Ae.
      aegypti. The success of these control methods will depend on the population
      structure of the target species including population size and rates of movement
      among populations. Releases of modified mosquitoes could target local populations
      that show a high degree of isolation from surrounding populations, potentially
      allowing new variants to become established in one region with eventual dispersal
      to other regions.

PMID- 19769039
TI  - First record of a new member of Anopheles Hyrcanus Group from Iran: molecular
      identification, diagnosis, phylogeny, status of kdr resistance and Plasmodium
      infection.
AB  - The current study aimed to provide further evidence on the status of species
      composition, insecticide resistance, and vectorial capacity within the members of
      Anopheles (Anopheles) Hyrcanus Group in Ardebil, Giulan, and Khuzestan provinces
      of Iran. Sequencing the internal transcribed spacer 2 (ITS2) of ribosomal DNA
      gene led to identification of two members of Hyrcanus complex: Anopheles hyrcanus
      Pallas and a new species/form, hereafter called Anopheles hyrcanus sp(IR) as a
      world record. Furthermore, we identified and compared partial sequences of exons
      I and II and the whole intron I region of insecticide resistance-related voltage
      gated sodium channel (vgsc) gene in populations of Hyrcanus Group and other main
      old world Anopheles species. The ITS2 and vgsc sequences in members of Hyrcanus
      Group and other Anopheles species were used for construction of phylogenetic
      tree, which demonstrated the evolutionary relatedness among Western and Eastern
      Palearctic taxa within the Hyrcanus Group. A nested polymerase chain reaction
      assay for detection of Plasmodium species revealed the infection of Plasmodium
      falciparum within An. hyrcanus collected from Fooman district in Guilan province.
      The data from this study led to the introduction of a new member/form within the
      Hyrcanus Group, identification and definition of the status of knockdown
      resistance related to pyrethroids and DDT in their vgsc gene, detection of
      Plasmodium infection, and further evidence on genetic relatedness within these
      taxa. The overall results may suggest reconsidering the role ofAn. hyrcanus in
      malaria transmission, which would be useful for implementation and evaluation of
      malaria control programs in Western Palearctic region.

PMID- 19769040
TI  - Phlebotomus perfiliewi transcaucasicus, a vector of Leishmania infantum in
      northwestern Iran.
AB  - Visceral leishmaniasis is caused by Leishmania infantum, which is transmitted to
      humans by bites of phlebotomine sand flies and is one of the most important
      public health problems in Iran. To identify the vector(s), an investigation was
      carried out in Germi district, an important focus of the disease in Ardebil
      province in northwestern Iran, during July-September 2004 and 2005. Using sticky
      papers, CDC light traps and aspirators, 3,560 sand flies were collected and
      identified to species. Host bloodmeal preference and Leishmania infections in
      female specimens were evaluated using enzyme-linked immunosorbent assay (ELISA)
      for the former and microscopic examination followed by polymerase chain reaction
      (PCR) assay using species-specific kinetoplast minicircle primers for the latter.
      Nine sand fly species are present in the district, including Phlebotomus
      kandelakii Shchurenkova, Phlebotomus perfiliewi transcaucasicus Perfil'ev,
      Phlebotomus major Annandale, Phlebotomus balcanicus Theodor, Phlebotomus
      halepensis Theodor, Phlebotomus brevis Theodor & Meshghali, Phlebotomus papatasi
      Scopoli, Sergentomyia dentata Sinton, and Sergentomyia sintoni Pringle, with P.
      p. transcaucasicus being the most prevalent representative of the genus
      Phlebotomus at 45%. The anthropophilic index for P. p. transcaucasicus was 36.3%,
      indicating a strong preference for humans. Of 905 female P. p. transcuacasicus
      dissected, 10 (1.1%) were found naturally infected with promastigotes. Species
      specific amplification of promastigotes eluted from Giemsa-stained slides
      revealed specific PCR products of L. infantum DNA. Based on its high
      anthropophily and natural infections with L. infantum, and the fact that it was
      the only species found infected with L. infantum, we conclude that P. p.
      transcaucasicus is the principal vector of L. infantum in northwestern Iran.

PMID- 19769041
TI  - Characterization of internal transcribed spacer (ITS1)-ITS2 region of ribosomal
      RNA gene from 25 species of Culicoides biting midges (Diptera: Ceratopogonidae)
      in Japan.
AB  - We determined nucleotide sequences of the nuclear rDNA internal transcribed
      spacer (ITS)1-5.8S-ITS2a-2S-ITS2 region in 103 individuals of 25 Culicoides
      species (Diptera: Ceratopogonidae) from 11 locations in Japan. Ribosomal RNA
      genes, 5.8S and 2S rDNA, were highly conserved among the species with few
      variations. The ITS2a region showed length variation among species. Both ITS1 and
      ITS2 showed highly varied sequences among species. The noticeable indel regions
      among ITS1 sequences are present in some Culicoides species, separating species
      into two types having long or short ITS1 region. However, Culicoides cylindratus
      Kitaoka possesses both types of ITS1 in each individual; these results seem to
      indicate that the ITS1-long type was the prototype and the short type was
      produced through deletion in many Culicoides species. One species, belonging to
      subgenus Avaritia, possessed an Avaritia-specific sequence in ITS1 and
      phylogenetically formed a monophyletic group. Geographical genotypes in a species
      were not clear. Species-specific sequence features were observed, enabling
      molecular identification of Culicoides species.

PMID- 19769042
TI  - A database of expressed genes from Cochliomyia hominivorax (Diptera:
      Calliphoridae).
AB  - We used an expressed sequence tag and 454 pyrosequencing approach to initiate a
      study of the genome of the screwworm, Cochliomyia hominivorax (Coquerel)
      (Diptera: Calliphoridae). Two normalized cDNA libraries were constructed from RNA
      isolated from embryos and second instar larvae from the Panama 95 strain.
      Approximately 5,400 clones from each library were sequenced from both the 5' and
      3' directions using the Sanger method. In addition, double-stranded cDNA was
      prepared from random-primed polyA RNA purified from embryos, second-instar
      larvae, adult males, and adult females. These four cDNA samples were used for 454
      pyrosequencing that produced approximately 300,000 independent sequences.
      Sequences were assembled into a database of assembled contigs and singletons and
      used to search public protein databases and annotate the sequences. The full
      database consists of 6,076 contigs and 58,221 singletons assembled from both the
      traditional expressed sequence tag (EST) and 454 sequences. Annotation of the
      data led to the identification of several gene coding regions with possible roles
      in sex determination in the screwworm. This database will facilitate the design
      of microarray and other experiments to study screwworm gene expression on a
      larger scale than previously possible.

PMID- 19769043
TI  - Dispersal and survival of male and female Aedes albopictus (Diptera: Culicidae)
      on Reunion Island.
AB  - Mouse-baited traps were used to assess the longevity and dispersal of male and
      female Aedes albopictus by mark-release-recapture at two sites on La Reunion
      Island. Recapture rate was high, and mosquitoes of both sexes appeared up to 23 d
      after release. A daily survival probability of approximately 0.95 for males and
      females, far higher than expected, was estimated from these results. There was
      evidence that both sexes prefer to follow corridors of vegetation rather than
      crossing open spaces. Populations of wild mosquitoes had parous and insemination
      rates indicative of a young population. These results are relevant to future
      attempts to control this species by sterile insect technology.

PMID- 19769044
TI  - Effect of fruit and leaves of Meliaceae plants (Azadirachta indica and Melia
      azedarach) on the development of Lutzomyia longipalpis larvae (Diptera:
      Psychodidae: Phlebotominae) under experimental conditions.
AB  - This no-choice, laboratory study focuses on the feeding of dried, ground,
      homogeneous powdered, unprocessed fruit and leaves of Azadirachta indica and
      Melia azedarach to Lutzomyia longipalpis larvae to determine the effects on their
      mortality and metamorphosis. A. indica and M. azedarach fruit and leaves
      significantly increased larval mortality in comparison to larvae fed the
      untreated, standard diet. A. indica fruit and leaves blocked the molting of the
      larvae to the fourth instar, resulting in them remaining as third instars until
      the end of the experiment. M. azedarach fruit also blocked the molting of larvae,
      which remained permanently in the fourth instar. Feeding M. azedarach leaves
      resulted in greater molt inhibition. All insects in this group stopped their
      development as second-instar larvae. No antifeedant effect was detected for any
      experimental treatment. The results indicate that nontoxic, unprocessed materials
      obtained from A. indica and M. azedarach are potent development inhibitors of L.
      longipalpis larvae.

PMID- 19769045
TI  - Evaluation of rhodamine B as an orally delivered biomarker for rodents and a feed
      through transtadial biomarker for phlebotomine sand flies (Diptera: Psychodidae).
AB  - The purpose of this study was to evaluate the use of rhodamine B as an orally
      delivered biomarker for rodents and a feed-through transtadial biomarker for
      phlebotomine sand flies (Diptera: Psychodidae). Rhodamine B-treated hamsters were
      visibly marked for up to 8 wk, and their feces were fluorescent when examined
      under a fluorescence microscope. The development and survival of sand fly larvae
      fed feces of rhodamine B-treated hamsters were not significantly different from
      control sand flies. Adult male and female sand flies, that had been fed as larvae
      the feces of rhodamine B-treated hamsters, were fluorescent when examined using
      fluorescent microscopy and could be distinguished from control sand flies. Adult
      female sand flies that took bloodmeals from rhodamine B-treated hamsters were
      fluorescent when examined immediately after feeding. Rhodamine B incorporated
      rodent baits could be used to detect adult male and female sand flies that fed on
      the feces of baited rodents as larvae, or adult female sand flies that have taken
      a bloodmeal from bait-fed rodents. This would allow the delineation of specific
      foci with rodent-sand fly associations that would be susceptible to control by
      using feed-through or systemic insecticides.

PMID- 19769046
TI  - Effect of prescribed fire for tick control in California chaparral.
AB  - Prescribed fire was investigated as a method for controlling ixodid and argasid
      ticks in chaparral habitats in northern California. Two experimental and two
      adjacent control plots within a wildlife preserve were monitored for 1 yr
      postburn. Ticks were collected by flagging vegetation, by CO2-baited pitfall
      trap, and by live-trapping rodents. Twice as many rodents were caught at control
      sites compared with burn sites and no dusky-footed woodrats, Neotoma fuscipes
      Baird, were found in the treatment sites postburn. This species is known to be a
      reservoir of the agents of Lyme disease, Borrelia burgdorferi sensu stricto
      Johnson, Schmid, Hyde, Steigerwalt & Brenner, and human granulocytic
      anaplasmosis, Anaplasma phagocytophilum Dumler, Barbet, Bekker, Dasch, Palmer,
      Ray, Rikihisa, Rurangirwa. Six ixodid tick species were removed from rodents
      (Ixodes pacificus Cooley & Kohls, Ixodes jellisoni Cooley & Kohls, Ixodes
      spinipalpis Hadwen & Nuttall, Ixodes woodi Bishopp, Dermacentor occidentalis
      Marx, and Dermacentor parumapertus Neumann), two of which transmit bacterial
      zoonotic agents to people in the far-western United States. There was no decrease
      in number of ticks per animal trapped at either burn site compared with controls;
      in fact, the mean number of immature I. pacificus per rodent was significantly
      higher at one burn site than its control site. Soil refugia may protect ticks
      from fire-induced mortality; the argasid tick Ornithodoros coriaceus Koch, which
      lives in soil, was unaffected by the prescribed fire as were I. pacificus and D.
      occidentalis buried in packets 2.5 cm below ground. We conclude that although
      prescribed fires in chaparral habitats may diminish local rodent abundance, it
      does not decrease tick loads on rodents. Furthermore, burning chaparral does not
      result in a decreased abundance of adult ixodid ticks on vegetation and
      apparently does not affect argasid or ixodid ticks that are sheltered within soil
      refugia.

PMID- 19769047
TI  - Siphonaptera associated with wild mammals from the Central Atlantic Forest
      Biodiversity Corridor in southeastern Brazil.
AB  - We collected 379 samples of eight flea species from 235 specimens of wild mammals
      captured in three areas of the Central Atlantic Forest Corridor in the state of
      Espirito Santo, southeastern Brazil, between August 2006 and February 2008. Among
      the 22 mammal species, we found eight species of marsupials (order
      Didelphimorphia), 13 species of rodents (order Rodentia), and one species of wild
      cat (order Carnivora). The total prevalence of infestation was 28.1%, with
      similar percentages in rodents (26.4%) and marsupials (29.5%). The infestation in
      the southern area was 3 times higher than that observed in the northern area. The
      infestation by single flea species was > 6 times higher than the total number of
      double and triple infestations. The mean abundance of fleas was 1.61. The flea
      female/male ratio was 1.38, ranging from 0.95 in Adoratopsylla (Tritopsylla)
      intermedia intermedia (Wagner) to 1.81 in Hechtiella nitidus (Johnson) in the
      most flea species infested. We report three new records of flea species in the
      state of Espirito Santo, and eight new host records.

PMID- 19769048
TI  - Aedes triseriatus females transovarially infected with La Crosse virus mate more
      efficiently than uninfected mosquitoes.
AB  - The mating efficiencies (the percentage of females inseminated by males) of field
      collected and laboratory-colonized Aedes triseriatus (Say) (Diptera: Culicidae)
      female mosquitoes transovarially infected or uninfected with La Crosse virus
      (LACV) were compared. The females were placed in cages with age-matched males,
      and the insemination rates (number of inseminated females of the total number of
      females examined) were determined daily by detection of sperm in the
      spermathecae. LACV-infected mosquitoes typically mated earlier than uninfected
      mosquitoes, i.e., insemination occurred earlier after the mixing of males and
      females. LACV load was not correlated with increased insemination.

PMID- 19769049
TI  - Natural infection of Lutzomyia neivai and Lutzomyia sallesi (Diptera:
      Psychodidae) by Leishmania infantum chagasi in Brazil.
AB  - Natural infections with Leishmania were found in females of the phlebotomine sand
      flies Lutzomyia neivai (Pinto) (= Nyssomyia neivai) and Lutzomyia sallesi (Galvao
      & Coutinho) (= Evandromyia sallesi) (Diptera: Psychodidae) from Lassance, in the
      Brazilian state of Minas Gerais. Promastigotes were found in the pyloric region
      of the former species and in the abdominal midgut of the latter species. Insects
      found to be infected by microscopic examination were macerated in saline solution
      and inoculated into hamsters. Subsequent analysis by polymerase chain reaction
      restriction fragment length polymorphism revealed both isolates to belong to the
      species Leishmania infantum chagasi Cunha & Chagas.

PMID- 19769050
TI  - Comprehensive study on the occurrence and distribution of pathogenic
      microorganisms carried by synanthropic flies caught at different rural locations
      in Germany.
AB  - In the current study, samples of 50 synanthropic flies were collected from each
      of five rural locations used for domestic animal husbandry (specifically a cattle
      barn, a dog pound, a horse stable, and a pigpen). Flies were examined using a
      variety of microbiological methods to determine the pathogenic agents that they
      carried. The most frequently sampled species were Musca domestica (L.) (51%)
      followed by Stomoxys calcitrans (L.) (24%). All fly species were found to carry
      an array of different pathogenic bacterial and fungal species. Among these were
      human pathogens such as Campylobacter jejuni and Escherichia coli-strains (EHEC,
      EPEC, and ETEC) and the fungi Candida albicans and Candida tropicalis. The germs
      could be detected in the intestines as well as on the exoskeletons of the flies.
      The current study confirms and supplements the general knowledge about pathogens
      that may be transmitted to domestic animals and humans by synanthropic flies.

PMID- 19769051
TI  - Determination of mosquito (Diptera: Culicidae) bloodmeal sources in Western
      Australia: implications for arbovirus transmission.
AB  - A double-antibody enzyme-linked immunosorbent assay was used to determine the
      bloodmeal sources of adult mosquitoes (Diptera: Culicidae) collected in
      encephalitis vector surveillance mosquito traps in Western Australia between May
      1993 and August 2004. In total, 2,606 blood-fed mosquitoes, representing 29
      mosquito species, were tested, and 81.7% reacted with one or more of the primary
      antibodies. Aedes camptorhynchus (Thomson) and Culex annulirostris Skuse were the
      most common species tested, making up 47.2% (1,234) and 35.6% (930),
      respectively. These species obtained bloodmeals from a variety of vertebrate
      hosts but particularly marsupials and cows. In contrast, Culex pullus Theobald
      (72.7%; 24/33), Culiseta atra (Lee) (70.0%; 7/10), Culex globocoxitus
      Dobrotworsky (54.5%; 12/22), and Culex quinquefasciatus Say (39.3%; 22/56) often
      obtained bloodmeals from birds. Although Ae. camptorhynchus and Cx. annulirostris
      are well established vectors of arboviruses, other mosquitoes also may have a
      role in enzootic and/ or epizootic transmission.

PMID- 19769052
TI  - Patterns of Aedes aegypti (Diptera: Culicidae) infestation and container
      productivity measured using pupal and Stegomyia indices in northern Argentina.
AB  - A citywide control program of Aedes aegypti (L.) (Diptera: Culicidae) mainly
      based on the use of larvicides reduced infestations but failed to achieve the
      desired target levels in Clorinda, northeastern Argentina, over 5 yr of
      interventions. To understand the underlying causes of persistent infestations and
      to develop new control tactics adapted to the local context, we conducted two
      pupal surveys in a large neighborhood with approximately 2,500 houses and
      recorded several variables for every container inspected in fall and spring 2007.
      In total, 4,076 lots and 4,267 containers were inspected over both surveys, and
      8,391 Ae. aegypti pupae were collected. Large tanks used for potable water
      storage were the most abundant and the most productive type of container,
      accounting for 65-84% of all the pupae collected. Therefore, large tanks were key
      containers and candidates for improved targeted interventions. Multivariate
      analysis showed that containers located in the yard, at low sun exposure,
      unlidded, filled with rain water, and holding polluted water were all more likely
      to be infested by larvae or pupae. When only infested containers were considered,
      productivity of pupae was most closely associated with large tanks and rain
      water. A stochastic simulation model was developed to calculate the expected
      correlations between pupal and Stegomyia indices according to the characteristics
      of the distribution of larvae and pupae per container and the spatial scale at
      which the indices were computed. The correlation between pupal and Stegomyia
      indices is expected to increase as infestation levels decline.

PMID- 19769053
TI  - Habitat preferences of phlebotomine sand flies (Diptera: Psychodidae) in
      southwestern Morocco.
AB  - Data from a 4-yr study of phlebotomine sand flies in 44 stations in southwestern
      Morocco are presented. Correspondence analysis is used to describe the habitat
      preferences of nine sand fly species on a meso-scale (station) and a micro-scale
      (biotope). This work, based on highly diversified data from various stations,
      comprising several biotopes sampled during different seasons, provides new
      information on the ecology of sand flies in southwestern Morocco. It highlights
      many natural and artificial factors that affect the abundance and distribution of
      sand fly populations. The impact of climate, urbanization, proximity of humans
      and domestic animals, organic matter in the soil, shelter, and vegetation type is
      discussed.

PMID- 19769054
TI  - First finding of melanic sylvatic Triatoma infestans (Hemiptera: Reduviidae)
      colonies in the Argentine Chaco.
AB  - Triatoma infestans (Klug), the most important vector of Chagas disease in
      southern South America, is a highly domiciliated species with well-known sylvatic
      foci only in the Bolivian Andean valleys and in the Bolivian Chaco, where melanic
      insects designated as "dark morphs" were found. After the tentative
      identification of two melanic bugs collected from parrot nests in a forest
      reserve in the Argentine Chaco as T. infestans, we conducted an intensive search
      there using mouse-baited sticky traps in summer 2006 and 2007. Four live T.
      infestans bugs were collected in trees without parrot nests in 288 trap-nights,
      whereas no bug was collected from inside trees with active parrot nests in 51
      trap-nights. To increase bug captures, hollow tree trunks that recently had had
      Amazona aestiva (Berlepsch) and Aratinga acuticaudata (Vieillot) parrot nests
      were treated with insecticide fumigant canisters exhibiting strong knockdown
      power. Four (22%) of 18 trees were positive for T. infestans with a dark
      phenotype. A fragment of the mitochondrial gene COI of 8 of the 14 triatomine
      bugs collected was successfully sequenced and confirmed as T. infestans. Most of
      the bugs were captured from Aspidosperma quebracho-blanco (Schlechter) hollow
      tree trunks harboring parrot nests. All of the T. infestans collected from the
      nearest house located at 10 km from the sylvatic foci displayed normal chromatic
      characters. The repeated finding of T. infestans in sylvatic habitats, albeit at
      very low density, shows that this species is capable of maintaining viable
      sylvatic foci in the absence of human hosts and immigration from domestic
      populations. These are the first confirmed findings of sylvatic T. infestans
      colonies in Argentina and of dark morphs in the Argentine Chaco.

PMID- 19769056
TI  - Hymenopteran parasitoids of forensic importance: host associations, seasonality,
      and prevalence of parasitoids of carrion flies in Western Australia.
AB  - A 2-yr survey of hymenopteran parasitoids associated with carrion-breeding flies
      was conducted to establish the parasitoid species of potential forensic
      significance in Western Australia. Host associations, seasonality, and rates of
      parasitism in the field were examined to assess the value of the identified
      parasitoids as forensic indicators of time since death. Four species of
      parasitoid emerged from dipteran specimens collected from carcasses:
      Tachinaephagus zealandicus Ashmead (Encryptidae), Nasonia vitripennis Walker
      (Pteromalidae), Spilomicrus sp. (Diapriidae), and Aphaereta sp. (Braconidae).
      Overall parasitism of carrion-breeding flies was 11.8%. T. zealandicus and N.
      vitripennis were the predominant species, accounting for 86.3 and 11.5% of
      parasitism observed, respectively. In contrast, Aphaereta sp. and Spilomicrus sp.
      were intermittently collected from carcasses throughout the study and the
      parasitism rates of both species were low (< or = 3.0%). Our findings provide
      forensically important biological and behavioral data of parasitoid-host
      interactions within carcass environments. The cosmopolitan parasitoids T.
      zealandicus and N. vitripennis have the greatest potential as indicators of time
      since death in forensic investigations based on their broad host ranges, rates of
      parasitism, and seasonal prevalence. In combination, these two species are
      present throughout the year and they parasitized nearly all of the dipteran
      species that colonize carcasses. Because both are cosmopolitan species, the data
      presented here are applicable to regions experiencing a similar Mediterranean
      climate. This work reports the first incidence of T. zealandicus and N.
      vitripennis parasitizing the dipteran species Calliphora albifrontalis Malloch
      (Calliphoridae), Calliphora dubia Macquart (Calliphoridae), and Hydrotaea
      rostrata Robineau-Desvoidy (Muscidae).

PMID- 19769057
TI  - Changes in Aedes albopictus (Diptera: Culicidae) populations in New Jersey and
      implications for arbovirus transmission.
AB  - The Asian tiger mosquito Aedes albopictus (Skuse) was first detected in New
      Jersey in 1995 during mosquito surveillance operations in Monmouth County. We
      tracked statewide changes in populations of the Asian tiger mosquito and its
      association with West Nile virus from 2003 to 2007. Ae. albopictus population
      abundance has increased in New Jersey since 2003, primarily along the urban
      corridor between New York City and Philadelphia, and they are now expanding their
      range further into suburban and rural areas of the state. Ae. albopictus has
      invaded all counties of New Jersey except for two northwest rural counties
      (Sussex and Warren). West Nile virus was detected in Ae. albopictus throughout
      several foci in New Jersey during the study, underscoring the public health
      significance of this mosquito.

PMID- 19769055
TI  - Stone Lakes virus (family Togaviridae, genus Alphavirus), a variant of Fort
      Morgan virus isolated from swallow bugs (Hemiptera: Cimicidae) west of the
      Continental Divide.
AB  - Multiple isolates of an alphaviruses within the western equine encephalomyelitis
      serocomplex that were related closely to Ft. Morgan and its variant Buggy Creek
      virus were made from swallow bugs, Oeciacus vicarius Horvath (Hemiptera:
      Cimicidae), collected from cliff swallow (Petrochelidon pyrrhonota) nests at the
      Stone Lakes National Wildlife Refuge, Sacramento County, CA, during the summers
      of 2005 and 2006. This virus (hereafter Stone Lakes virus, family Togaviridae,
      genus Alphavirus, STLV) was the first record of this viral group west of the
      Continental Divide. STLV replicated well in Vero and other vertebrate cell
      cultures but failed to replicate in C6/36 cells or infect Culex tarsalis
      Coquillett mosquitoes. STLV failed to produce elevated viremias in adult chickens
      or house sparrows and was weakly immunogenic. In addition, STLV was not isolated
      from cliff swallow nestlings nor was antibody detected in adults collected at
      mist nets. We suggest that STL and related swallow bug viruses may be primarily
      infections of cimicids that are maintained and amplified either by vertical or
      nonviremic transmission and that cliff swallows may primarily be important as a
      bloodmeal source for the bugs rather than as an amplification host for the
      viruses.

PMID- 19769058
TI  - Ticks (Acari: Ixodidae) infesting birds in an Atlantic rain forest region of
      Brazil.
AB  - Brazil has the third richest bird diversity of the world; however, there are few
      data concerning ticks (Acari: Ixodidae) parazitizing birds. The aim of the study
      was to report tick infestations on wild birds from an Atlantic rain forest region
      of Brazil. During 2 yr, ticks were collected from birds and from the environment
      in 12 forest sites. A total of 1,725 birds were captured representing 80 species
      from 24 families. In total, 223 (13%) birds were found infested by immature
      stages of Amblyomma ticks: 1,800 larvae and 539 nymphs. The prevalence of ticks
      was higher among birds from the families Thamnophilidae, Conopophagidae, and
      Momotidae. The most common tick parasitizing birds was Amblyomma nodosum Koch.
      Other tick species, Amblyomma coelebs Neumann, Amblyomma cajennense (F.),
      Amblyomma ovale Koch, Amblyomma longirostre (Koch), Amblyomma calcaratum Neumann,
      and Amblyomma naponense (Packard), were found sporadically. Among free-living
      ticks collected in the environment, A. cajennense was the most common, followed
      by A. coelebs, A. naponense, Amblyomma brasilense Aragao, and Hemaphysalis
      juxtakochi Cooley.

PMID- 19769060
TI  - Bloodmeal mass and oviparity mediate host avidity and DEET repellency in Aedes
      albopictus (Diptera: Culicidae).
AB  - This study was made to determine the effects of bloodmeal mass and oviparity in
      Aedes albopictus (Skuse) (Diptera: Culicidae) on continued host-seeking activity
      in female mosquitoes and efficacy of the repellent N,N-diethyl-3-methylbenzamide
      (DEET). There was a curvilinear relationship between bloodmeal mass in partially
      fed Ae. albopictus and host avidity with a threshold between 0.8 and 1.0 mg of
      ingested blood for reduced host seeking by female mosquitoes. Egg development and
      fecundity were related to bloodmeal mass, which also evoked significantly
      different mean host seeking rates in nulliparous and parous Ae. albopictus. The
      repellency of DEET to partially blood fed female mosquitoes depended on oviparity
      status and host avidity with repellent failure soonest in partially blood fed
      nullipars.

PMID- 19769059
TI  - Bloodmeal identification and detection of avian malaria parasite from mosquitoes
      (Diptera: Culicidae) inhabiting coastal areas of Tokyo Bay, Japan.
AB  - Bloodmeal identification and the detection of avian malaria parasite from
      mosquitoes (Diptera: Culicidae) were carried out by polymerase chain reaction
      based methods for field samples collected in coastal areas of Tokyo Bay, Japan,
      from April to October 2007. The following seven mosquito species were collected:
      Aedes albopictus (Skuse), Culex pipiens pallens Coquillett, Culex pipiens form
      molestus Forskal, Culex tritaeniorhynchus Giles, Culex inatomii Kamimura & Wada,
      Culex bitaeniorhynchus Giles, and Lutzia vorax Edwards. Forty blood-fed
      mosquitoes were collected and 95% of bloodmeals of Cx. pipiens pallens were avian
      derived, whereas only mammalian bloodmeals were identified for Ae. albopictus.
      Plasmodium DNA was amplified from 65% (15/23) of blood-fed Cx. pipiens pallens
      and unfed females of Cx. pipiens pallens and Cx. pipiens form molestus with a
      minimum infection rate of 29.9 and 13.5, respectively. One unfed female of Lt.
      vorax was also positive for Plasmodium parasites. Five genetically distinct
      lineages of Plasmodium were identified, with 0.21 to 5.86% sequence divergence.
      Rinshi-8, the most prevalent lineage at our study site, was identical to the
      published sequence of Plasmodium relictum-P5.

PMID- 19769061
TI  - Sensitivity of host-seeking nymphal lone star ticks (Acari: Ixodidae) to
      immersion in heated water.
AB  - Host-seeking nymphal Amblyomma americanum (L.) (Acari: Ixodidae) were placed into
      heated water, and their survival or their torpidity was recorded as a function of
      exposure time. Exposures were determined that either kill the nymphs or affect
      their mobility. All nymphs died when exposed for a minute or more to a
      temperature > 51 degrees C. Nearly all nymphs remained motionless for a period of
      time when exposed for 3 min to a temperature > 44 degrees C.

PMID- 19769062
TI  - [Is the patient's diagnosis correct? "Doctor, my pacemaker has exploded"!].

PMID- 19769063
TI  - [New biomarker discovered. Will the diagnosis of neuroborreliosis soon be easier
      (interview by Maria Weiss)?].

PMID- 19769064
TI  - [Dietary recommendations for type 2 diabetic patients. Satiety despite weight
      loss].

PMID- 19769065
TI  - [A comprehensive therapeutic strategy for the asthmatic patient. Medication
      according to need is not enough].

PMID- 19769066
TI  - [Modern pain therapy with dual advantage. Strong analgesia and superior
      tolerance].

PMID- 19769067
TI  - [Tolerated opioid therapy with oxycodone/naloxone. Better quality of life for
      osteoporosis patients].

PMID- 19769068
TI  - [Stigmatization, metabolic trouble, drug resistance: current challenges in HIV
      therapy].

PMID- 19769069
TI  - [How to talk about HIV infection].

PMID- 19769070
TI  - [Epidemiology of the HIV infection].

PMID- 19769071
TI  - [Scientific round table--highlights of the 16th CROI 2009. Focus on current
      therapy studies].

PMID- 19769072
TI  - [Medication change due to side effects or possible long-term complications. Side
      effect management with vision].

PMID- 19769073
TI  - [HAART influences the lipids].

PMID- 19769074
TI  - [Treatment of facial lipatrophy].

PMID- 19769075
TI  - [HIV infection in women].

PMID- 19769076
TI  - [Therapy of HIV-HBV-coinfection].

PMID- 19769077
TI  - [One year with Atripla. Changeover to complete HIV therapy in a single tablet has
      proven successful].

PMID- 19769078
TI  - [Causes of death in HIV patients].

PMID- 19769079
TI  - [Highly active antiretroviral therapy].

PMID- 19769080
TI  - [Telbivudine in the management of HIV/HBV coinfection. Treating hepatitis B
      without HIV trouble].

PMID- 19769081
TI  - [New antiretroviral drug classes in HIV therapy].

PMID- 19769082
TI  - [Integrase inhibition].

PMID- 19769083
TI  - [Resistance screening].

PMID- 19769084
TI  - [Current data on antiretroviral therapy. CROI 2009: tenofovir DR convinces by
      high effectiveness and tolerance].

PMID- 19769085
TI  - [How HIV treatment can be simplified. "Once daily" as starter therapy is
      effective].

PMID- 19769086
TI  - [Preliminary first steps are encouraging. Gene therapy against HIV? (interview by
      Waldtraud Paukstadt)].

PMID- 19769087
TI  - Assessing fuel treatment effectiveness using satellite imagery and spatial
      statistics.
AB  - Understanding the influences of forest management practices on wildfire severity
      is critical in fire-prone ecosystems of the western United States. Newly
      available geospatial data sets characterizing vegetation, fuels, topography, and
      burn severity offer new opportunities for studying fuel treatment effectiveness
      at regional to national scales. In this study, we used ordinary least-squares
      (OLS) regression and sequential autoregression (SAR) to analyze fuel treatment
      effects on burn severity for three recent wildfires: the Camp 32 fire in western
      Montana, the School fire in southeastern Washington, and the Warm fire in
      northern Arizona. Burn severity was measured using differenced normalized burn
      ratio (dNBR) maps developed by the Monitoring Trends in Burn Severity project.
      Geospatial data sets from the LANDFIRE project were used to control for prefire
      variability in canopy cover, fuels, and topography. Across all three fires,
      treatments that incorporated prescribed burning were more effective than thinning
      alone. Treatment effect sizes were lower, and standard errors were higher in the
      SAR models than in the OLS models. Spatial error terms in the SAR models
      indirectly controlled for confounding variables not captured in the LANDFIRE
      data, including spatiotemporal variability in fire weather and landscape-level
      effects of reduced fire severity outside the treated areas. This research
      demonstrates the feasibility of carrying out assessments of fuel treatment
      effectiveness using geospatial data sets and highlights the potential for using
      spatial autoregression to control for unmeasured confounding factors.

PMID- 19769088
TI  - Fire suppression and fuels treatment effects on mixed-conifer carbon stocks and
      emissions.
AB  - Depending on management, forests can be an important sink or source of carbon
      that if released as CO2 could contribute to global warming. Many forests in the
      western United States are being treated to reduce fuels, yet the effects of these
      treatments on forest carbon are not well understood. We compared the immediate
      effects of fuels treatments on carbon stocks and releases in replicated plots
      before and after treatment, and against a reconstruction of active-fire stand
      conditions for the same forest in 1865. Total live-tree carbon was substantially
      lower in modern fire-suppressed conditions (and all of the treatments) than the
      same forest under an active-fire regime. Although fire suppression has increased
      stem density, current forests have fewer very large trees, reducing total live
      tree carbon stocks and shifting a higher proportion of those stocks into small
      diameter, fire-sensitive trees. Prescribed burning released 14.8 Mg C/ha, with
      pre-burn thinning increasing the average release by 70% and contributing 21.9
      37.5 Mg C/ha in milling waste. Fire suppression may have incurred a double carbon
      penalty by reducing stocks and contributing to emissions with fuels-treatment
      activities or inevitable wildfire combustion. All treatments reduced fuels and
      increased fire resistance, but most of the gains were achieved with understory
      thinning, with only modest increases in the much heavier overstory thinning. We
      suggest modifying current treatments to focus on reducing surface fuels, actively
      thinning the majority of small trees, and removing only fire-sensitive species in
      the merchantable, intermediate size class. These changes would retain most of the
      current carbon-pool levels, reduce prescribed burn and potential future wildfire
      emissions, and favor stand development of large, fire-resistant trees that can
      better stabilize carbon stocks.

PMID- 19769089
TI  - Dynamics of aboveground carbon stocks in a selectively logged tropical forest.
AB  - The expansion of selective logging in tropical forests may be an important source
      of global carbon emissions. However, the effects of logging practices on the
      carbon cycle have never been quantified over long periods of time. We followed
      the fate of more than 60 000 tropical trees over 23 years to assess changes in
      aboveground carbon stocks in 48 1.56-ha plots in French Guiana that represent a
      gradient of timber harvest intensities, with and without intensive timber stand
      improvement (TSI) treatments to stimulate timber tree growth. Conventional
      selective logging led to emissions equivalent to more than a third of aboveground
      carbon stocks in plots without TSI (85 Mg C/ha), while plots with TSI lost more
      than one-half of aboveground carbon stocks (142 Mg C/ha). Within 20 years of
      logging, plots without TSI sequestered aboveground carbon equivalent to more than
      80% of aboveground carbon lost to logging (-70.7 Mg C/ha), and our simulations
      predicted an equilibrium aboveground carbon balance within 45 years of logging.
      In contrast, plots with intensive TSI are predicted to require more than 100
      years to sequester aboveground carbon lost to emissions. These results indicate
      that in some tropical forests aboveground carbon storage can be recovered within
      half a century after conventional logging at moderate harvest intensities.

PMID- 19769090
TI  - Soil carbon storage responses to expanding pinyon-juniper populations in southern
      Utah.
AB  - Over the past several decades, the expansion and thickening of woodlands in the
      western United States has caused a range of ecological changes. Woody expansion
      often leads to increases in soil organic matter (SOM) pools with implications for
      both biogeochemical cycling and ecological responses to management strategies
      aimed at restoration of rangeland ecosystems. Here we directly measure C and N
      stocks and use simple non-steady-state models to quantify the dynamics of soil C
      accumulation under and around trees of varied ages in southern Utah woodlands. In
      the two pinyon-juniper forests of Grand Staircase Escalante National Monument
      studied here, we found approximately 3 kg C/m2 and approximately 0.12 kg N/m2
      larger C and N stocks in soils under pinyon canopies compared to interspace
      sites. These apparent increases in soil C and N stocks under woody plant species
      were dominated by elevated SOM in the surface 10 cm of soil, particularly within
      non-mineral-associated organic fractions. The most significant accumulation of C
      was in the >850 microm fraction, which had an estimated C residence time of <20
      yr. Rates of carbon accumulation following pinyon-juniper expansion appear to be
      dominated by changes in this fast-cycling surface soil fraction. In contrast, we
      found that after separating >850 microm organic matter from the remaining light
      fraction (LF), C had residence times of approximately 400 yr and mineral
      associated (MA) soil C had residence times of approximately 600 yr. As a result,
      we calculate that input rates to the LF and MA pools to be 10 +/- 1 and 0.68 +/-
      0.15 g m(-2) yr(-1) (mean +/- SE), respectively. These findings suggest that one
      consequence of management activities aimed at the reduction of pinyon-juniper
      biomass may be a relatively rapid loss of soil C and N pools associated with the
      >850 microm fraction. The temporal dynamics of the <850 microm pools suggest that
      carbon and nitrogen continue to accumulate in these fractions, albeit at very
      slow rates, and suggest that multidecadal storage of C following tree recruitment
      is limited to relatively small, subsurface fractions of the total soil C pool.

PMID- 19769091
TI  - Near-surface remote sensing of spatial and temporal variation in canopy
      phenology.
AB  - There is a need to document how plant phenology is responding to global change
      factors, particularly warming trends. "Near-surface" remote sensing, using
      radiometric instruments or imaging sensors, has great potential to improve
      phenological monitoring because automated observations can be made at high
      temporal frequency. Here we build on previous work and show how inexpensive,
      networked digital cameras ("webcams") can be used to document spatial and
      temporal variation in the spring and autumn phenology of forest canopies. We use
      two years of imagery from a deciduous, northern hardwood site, and one year of
      imagery from a coniferous, boreal transition site. A quantitative signal is
      obtained by splitting images into separate red, green, and blue color channels
      and calculating the relative brightness of each channel for "regions of interest"
      within each image. We put the observed phenological signal in context by relating
      it to seasonal patterns of gross primary productivity, inferred from eddy
      covariance measurements of surface-atmosphere CO2 exchange. We show that spring
      increases, and autumn decreases, in canopy greenness can be detected in both
      deciduous and coniferous stands. In deciduous stands, an autumn red peak is also
      observed. The timing and rate of spring development and autumn senescence varies
      across the canopy, with greater variability in autumn than spring. Interannual
      variation in phenology can be detected both visually and quantitatively; delayed
      spring onset in 2007 compared to 2006 is related to a prolonged cold spell from
      day 85 to day 110. This work lays the foundation for regional- to continental
      scale camera-based monitoring of phenology at network observatory sites, e.g.,
      National Ecological Observatory Network (NEON) or AmeriFlux.

PMID- 19769092
TI  - Hawaiian native forest conserves water relative to timber plantation: species and
      stand traits influence water use.
AB  - Tropical forests are becoming increasingly alien-dominated through the
      establishment of timber plantations and secondary forests. Despite widespread
      recognition that afforestation results in increased evapotranspiration and lower
      catchment yields, little is known of the impacts of timber plantations on water
      balance relative to native forest. Native forest trees have been claimed to use
      water conservatively and enhance groundwater recharge relative to faster-growing
      alien species, and this argument should motivate native forest preservation and
      restoration. However, data have been available primarily for leaf-level gas
      exchange rather than for whole-plant and stand levels. We measured sap flow of
      dominant tree and tree fern species over eight weeks in native Metrosideros
      polymorpha forest and adjacent alien timber plantations on the island of Hawai'i
      and estimated total stand transpiration. Metrosideros polymorpha had the lowest
      values of sap flux density and whole-tree water use (200 kg m(-2) sapwood d(-1),
      or 8 kg/d for trees of 35 cm mean diameter at breast height, D), substantially
      less than timber species Eucalyptus saligna or Fraxinus uhdei (33 and 34 kg/d for
      trees of 73 and 30 cm mean D, respectively). At the stand level, E. saligna and
      F. uhdei trees had three- and ninefold higher water use, respectively, than
      native M. polymorpha trees. Understory Cibotium tree ferns were most abundant in
      M. polymorpha-dominated forest where they accounted for 70% of water use.
      Overall, F. uhdei plantation had the highest water use at 1.8 mm/d, more than
      twice that of either E. saligna plantation or M. polymorpha forest. Forest water
      use was influenced by species composition, stem density, tree size, sapwood
      allocation, and understory contributions. Transpiration varied strongly among
      forest types even within the same wet tropical climate, and in this case, native
      forest had strikingly conservative water use. Comparisons of vegetation cover in
      water use should provide additional resolution to ecosystem valuation and land
      management decisions.

PMID- 19769093
TI  - Sources of nutrients to windward agricultural systems in pre-contact Hawai'i.
AB  - Prior to European contact in 1778, Hawaiians developed intensive irrigated
      pondfield agricultural systems in windward Kohala, Hawai'i. We evaluated three
      potential sources of nutrients to windward systems that could have sustained
      intensive agriculture: (1) in situ weathering of primary and secondary minerals
      in upland soils; (2) rejuvenation of the supply of rock-derived nutrients on
      eroded slopes and in alluvium; and (3) transport of rock-derived nutrients to
      crops via irrigation water. Our results show that most windward soils are
      infertile and suggest that weathering of minerals within upland soils was
      insufficient to sustain intensive agriculture without substantial cultural
      inputs. Erosion enhances weathering and so increases nutrient supply, with soils
      of the largest alluvial valleys (>200 m deep) retaining 37% of calcium from
      parent material (compared to 2% in upland sites). However, soils of smaller
      valleys that also supported pre-contact agricultural systems are substantially
      less enriched. Isotopic 87Sr/86Sr analyses of stream water demonstrate that at
      low to moderate stream flow over 90% of dissolved strontium derives from
      weathering of basalt rather than deposition of atmospheric sources; most other
      dissolved cations also derive from basalt weathering. We calculate that
      irrigation water could have supplied approximately 200 kg ha(-1) yr(-1) of
      calcium to pondfield systems, nearly 100 times more than was supplied by
      weathering in soils on stable geomorphic surfaces. In effect, irrigation waters
      brought nutrients from rocks to the windward crops.

PMID- 19769094
TI  - Sugar maple growth in relation to nutrition and stress in the northeastern United
      States.
AB  - Sugar maple, Acer saccharum, decline disease is incited by multiple disturbance
      factors when imbalanced calcium (Ca), magnesium (Mg), and manganese (Mn) act as
      predisposing stressors. Our objective in this study was to determine whether
      factors affecting sugar maple health also affect growth as estimated by basal
      area increment (BAI). We used 76 northern hardwood stands in northern
      Pennsylvania, New York, Vermont, and New Hampshire, USA, and found that sugar
      maple growth was positively related to foliar concentrations of Ca and Mg and
      stand level estimates of sugar maple crown health during a high stress period
      from 1987 to 1996. Foliar nutrient threshold values for Ca, Mg, and Mn were used
      to analyze long-term BAI trends from 1937 to 1996. Significant (P < or = 0.05)
      nutrient threshold-by-time interactions indicate changing growth in relation to
      nutrition during this period. Healthy sugar maples sampled in the 1990s had
      decreased growth in the 1970s, 10-20 years in advance of the 1980s and 1990s
      decline episode in Pennsylvania. Even apparently healthy stands that had no
      defoliation, but had below-threshold amounts of Ca or Mg and above-threshold Mn
      (from foliage samples taken in the mid 1990s), had decreasing growth by the
      1970s. Co-occurring black cherry, Prunus serotina, in a subset of the
      Pennsylvania and New York stands, showed opposite growth responses with greater
      growth in stands with below-threshold Ca and Mg compared with above-threshold
      stands. Sugar maple growing on sites with the highest concentrations of foliar Ca
      and Mg show a general increase in growth from 1937 to 1996 while other stands
      with lower Ca and Mg concentrations show a stable or decreasing growth trend. We
      conclude that acid deposition induced changes in soil nutrient status that
      crossed a threshold necessary to sustain sugar maple growth during the 1970s on
      some sites. While nutrition of these elements has not been considered in forest
      management decisions, our research shows species specific responses to Ca and Mg
      that may reduce health and growth of sugar maple or change species composition,
      if not addressed.

PMID- 19769095
TI  - Fifty-five years of soil development in restored freshwater depressional
      wetlands.
AB  - Wetland restoration is increasingly used as a strategy both to address historical
      wetland losses and to mitigate new wetland impacts. Research has examined the
      success of restored wetlands for avifaunal habitat, plant biodiversity, and plant
      cover; however, less is known about soil development in these systems. Soil
      processes are particularly important as soil organic matter (SOM), cation
      exchange capacity (CEC), and other properties are directly linked to wetland
      functions such as water quality improvement. This research compared soil
      development processes and properties of 30 palustrine depressional wetlands of
      four different age classes (approximately 5, 14, 35, and 55 years since
      restoration) located in central New York (USA). Five natural wetlands were used
      as references. This chronosequence included wetlands 27 years older than
      previously conducted studies, making it the longest reported database available.
      Replicated soil cores from each site were analyzed for SOM, bulk density (D(b)),
      CEC, and concentrations of nutrients and other chemical constituents.
      Decomposition rate and aboveground plant and litter biomass were measured as key
      contributors to soil development. The results indicate that some soil properties
      critical for water quality functions take decades or centuries to reach natural
      reference levels. Of particular importance, in the top five centimeters of soil,
      SOM, D(b), and CEC achieved <50% of reference levels 55 years after restoration.
      Soil development processes in these depressional wetlands appear to be driven by
      autochthonous inputs and by internal processes such as litter decomposition and
      are not accelerated in the initial phase of development by allochthonous inputs
      as has been documented in coastal salt marshes and riverine floodplains. While
      monitoring generally focuses on the initial establishment phase of restored
      ecosystems, our findings indicate that the later autogenic phase strongly
      influences development trajectories for important wetland soil properties.
      Therefore, the role of different successional phases in determining long-term
      trajectories of ecosystem development should be considered in restoration design,
      research, and monitoring. This research highlights areas for improving the field
      of restoration through understanding of successional processes, increased efforts
      to jump-start soil development, longer-term monitoring programs, and greater
      focus on soil components of restored wetlands.

PMID- 19769096
TI  - Golf courses and wetland fauna.
AB  - Golf courses are often considered to be chemical-intensive ecosystems with
      negative impacts on fauna. Here we provide evidence that golf courses can
      contribute to the support and conservation of wetland fauna, i.e., amphibians and
      macroinvertebrates. Comparisons of amphibian occurrence, diversity of
      macroinvetebrates, and occurrence of species of conservation concern were made
      between permanent freshwater ponds surveyed on golf courses around Sweden's
      capital city, Stockholm, and off-course ponds in nature-protected areas and
      residential parklands. A total of 71 macroinvertebrate species were recorded in
      the field study, with no significant difference between golf course ponds and off
      course ponds at the species, genus, or family levels. A within-group similarities
      test showed that golf course ponds have a more homogenous species composition
      than ponds in nature-protected areas and ponds in residential parkland. Within
      the macroinvertebrate group, a total of 11 species of odonates were identified,
      with no difference detected between the categories of ponds, nor any spatial
      autocorrelation. Significant differences were found between pond categories in
      the occurrence of five species of amphibians, although anuran occurrence did not
      differ between ponds. The great crested newt (Triturus cristatus) was
      significantly associated with golf course ponds, but the smooth newt (Triturus
      vulgaris) was not. We found no evidence of any correlation between pond size and
      occurrence of amphibians. Among the taxa of conservation concern included in the
      sample, all amphibians are nationally protected in Sweden, with the
      internationally threatened T. cristatus more frequently found in golf course
      ponds. Among macroinveterbrates of conservation status, the large white-faced
      darter dragonfly (Leucorrhinia pectoralis) was only detected in golf course
      ponds, and Tricholeiochiton fagesi (Trichoptera) was only found in one off-course
      pond. GIS results revealed that golf courses provide over a quarter of all
      available permanent, freshwater ponds in central greater Stockholm. We assert
      that golf courses have the potential to contribute to wetland fauna support,
      particularly in urban settings where they may significantly contribute to wetland
      creation. We propose a greater involvement of ecologists in the design of golf
      courses to further bolster this potential.

PMID- 19769097
TI  - Improved water quality can ameliorate effects of climate change on corals.
AB  - The threats of wide-scale coral bleaching and reef demise associated with
      anthropogenic climate change are widely known. Moreover, rates of genetic
      adaptation and/or changes in the coral-zooxanthella partnerships are considered
      unlikely to be sufficiently fast for corals to acquire increased physiological
      resistance to increasing sea temperatures and declining pH. However, it has been
      suggested that coral reef resilience to climate change may be improved by good
      local management of coral reefs, including management of water quality. Here,
      using major data sets from the Great Barrier Reef (GBR), Australia, we
      investigate geographic patterns of coral bleaching in 1998 and 2002 and outline a
      synergism between heat stress and nutrient flux as a major causative mechanism
      for those patterns. The study provides the first concrete evidence for the oft
      expressed belief that improved coral reef management will increase the regional
      scale survival prospects of coral reefs to global climate change.

PMID- 19769098
TI  - Stable oxygen isotope reconstruction of ambient temperature during the collapse
      of a cod (Gadus morhua) fishery.
AB  - Changing environmental conditions set against a backdrop of high exploitation can
      result in severe consequences for commercially harvested stocks. The collapse of
      the Eastern Scotian Shelf cod (Gadus morhua L.) off eastern Canada was primarily
      due to overexploitation but may have been exacerbated by a widespread temperature
      decline. Recent studies have called for accurate determination of ambient
      temperature (the actual temperature exposure history of the fish) before
      discarding environmental conditions as a factor in the collapse. We used the
      stable oxygen isotope composition of otoliths (delta18O(oto)) to reconstruct the
      ambient temperature history of Eastern Scotian Shelf cod from 1970 to 2000 in
      order to determine whether the stock experienced the temperature decline or
      shifted their distribution to avoid it. To correct delta18O(oto) for seawater
      isotope content (deltaO(w)), we generated a new meta-equation for the
      relationship between delta18O(w) (per mil) and salinity (S, in psu) on the
      Eastern Scotian Shelf: delta18O(w) = 0.539 x S - 18.790. The ambient temperature
      series revealed that the large-scale geographic distribution of mature cod
      remained constant through the cooling period, although their ambient temperature
      was cooler than expected in warmer periods and warmer than expected in cooler
      periods, indicating small-scale thermoregulatory movement. Although the mean
      hydrographic temperature was 4 degrees C, mature cod usually inhabited the
      coldest available waters (mean ambient temperature = 3 degrees C), while the
      juveniles usually inhabited warmer waters (mean ambient temperature = 5.5 degrees
      C). Length-at-age was significantly related to ambient temperature, especially in
      the early years of growth, and therefore declining ambient temperatures were at
      least partially responsible for declines in asymptotic length (up to age 8 yr).
      The most active thermoregulatory movement occurred during a moderate warming
      period; therefore extreme warming events (such as those predicted under climate
      change) may force large-scale northward latitudinal shifts in this historically
      sedentary stock. Retroactive stable isotope chronologies can be an important tool
      in sustainable management strategies under the shifting climate conditions
      predicted for years to come.

PMID- 19769099
TI  - Selective significance of genome size in a plant community with heavy metal
      pollution.
AB  - In eukaryotes, nuclear genome sizes vary by more than five orders of magnitude.
      This variation is not related to organismal complexity, and its origin and
      biological significance are still disputed. One of the open questions is whether
      genome size has an adaptive role. We tested the hypothesis that genome size has
      selective significance, using five grassland communities occurring on a gradient
      of metal pollution of the soil as a model. We detected a negative correlation
      between the concentration of contaminating metals in the soil and the number of
      vascular plant species. Analysis of genome sizes of 70 herbaceous dicot perennial
      species occurring on the investigated plots revealed a negative correlation
      between the concentration of contaminating metals in the soil and the proportion
      of species with large genomes in plant communities. Consistent with the
      hypothesis, these results show that species with large genomes are at selective
      disadvantage in extreme environmental conditions.

PMID- 19769100
TI  - Influence of remediation in a mine-impacted river: metal trends over large
      spatial and temporal scales.
AB  - The effectiveness of mine-waste remediation at the Clark Fork River Superfund
      site in western Montana, USA, was examined by monitoring metal concentrations in
      resident biota (caddisfly, Hydropsyche spp.) and bed sediment over a 19-year
      period. Remediation activities began in 1990 and are ongoing. In the upper 45 km,
      reduced Cu and Cd concentrations at some sites were coincident with remediation
      events. However, for a period of three years, the decline in Cu and Cd directly
      below the treatment ponds was offset by high arsenic concentrations, suggesting
      that remediation for cations (e.g., Cu and Cd) mobilized anions such as arsenic.
      The impact of remediation in the middle and lower reaches was confounded by a
      significant positive relationship between metal bioaccumulation and stream
      discharge. High flows did not dilute metals but redistributed contaminants
      throughout the river. The majority of clean-up efforts were focused on reducing
      metal-rich sediments in the most contaminated upstream reach, implicitly assuming
      that improvements upstream will positively impact the downstream stations. We
      tested this assumption by correlating temporal metal trends in sediment between
      and among stations. The strength of that association (r value) was our indicator
      of spatial connectivity. Connectivity for both Cu and Cd was strong at small
      spatial scales. Large-scale connectivity was strongest with Cu since similar
      temporal reductions were observed at most monitoring stations. The most upstream
      station, closest to remediation, had the lowest connectivity, but the next three
      downstream sites were strongly correlated to trends downstream. Targeted
      remediation in this reach would be an effective approach to positively
      influencing the downstream stations.

PMID- 19769101
TI  - Interaction of historical and nonhistorical disturbances maintains native plant
      communities.
AB  - Historical disturbance regimes are often considered a critical element in
      maintaining native plant communities. However, the response of plant communities
      to disturbance may be fundamentally altered as a consequence of invasive plants,
      climate change, or prior disturbances. The appropriateness of historical
      disturbance patterns under modern conditions and the interactions among
      disturbances are issues that ecologists must address to protect and restore
      native plant communities. We evaluated the response of Artemisia tridentata ssp.
      wyomingensis (Beetle & A. Young) S.L. Welsh plant communities to their historical
      disturbance regime compared to other disturbance regimes. The historical
      disturbance regime of these plant communities was periodic fires with minimal
      grazing by large herbivores. We also investigated the influence of prior
      disturbance (grazing) on the response of these communities to subsequent
      disturbance (burning). Treatments were: (1) ungrazed (livestock grazing excluded
      since 1936) and unburned, (2) grazed and unburned, (3) ungrazed and burned
      (burned in 1993), and (4) grazed and burned. The ungrazed-burned treatment
      emulated the historical disturbance regime. Vegetation cover, density, and
      biomass production were measured the 12th, 13th, and 14th year post-burning.
      Prior to burning the presence of Bromus tectorum L., an exotic annual grass, was
      minimal (<0.5% cover), and vegetation characteristics were similar between grazed
      and ungrazed treatments. However, litter accumulation was almost twofold greater
      in ungrazed than in grazed treatments. Long-term grazing exclusion followed by
      burning resulted in a substantial B. tectorum invasion, but burning the grazed
      areas did not produce an invasion. The ungrazed-burned treatment also had less
      perennial vegetation than other treatments. The accumulation of litter (fuel) in
      ungrazed treatments may have resulted in greater fire-induced mortality of
      perennial vegetation in ungrazed compared to grazed treatments. Our results
      demonstrate that prior disturbances exert a strong influence on the response of
      plant communities to subsequent disturbances and suggest that low-severity
      disturbances may be needed in some plant communities to increase their resilience
      to more severe disturbances. Modern deviations from historical conditions can
      alter ecosystem response to disturbances, thus restoring the historical
      disturbance regime may not be an appropriate strategy for all ecosystems.

PMID- 19769102
TI  - Invasive Andropogon gayanus (gamba grass) is an ecosystem transformer of nitrogen
      relations in Australian savanna.
AB  - Invasion by the African grass Andropogon gayanus is drastically altering the
      understory structure of oligotrophic savannas in tropical Australia. We compared
      nitrogen (N) relations and phenology of A. gayanus and native grasses to examine
      the impact of invasion on N cycling and to determine possible reasons for
      invasiveness of A. gayanus. Andropogon gayanus produced up to 10 and four times
      more shoot phytomass and root biomass, with up to seven and 2.5 times greater
      shoot and root N pools than native grass understory. These pronounced differences
      in phytomass and N pools between A. gayanus and native grasses were associated
      with an altered N cycle. Most growth occurs in the wet season when, compared with
      native grasses, dominance of A. gayanus was associated with significantly lower
      total soil N pools, lower nitrification rates, up to three times lower soil
      nitrate availability, and up to three times higher soil ammonium availability.
      Uptake kinetics for different N sources were studied with excised roots of three
      grass species ex situ. Excised roots of A. gayanus had an over six times higher
      uptake rate of ammonium than roots of native grasses, while native grass Eriachne
      triseta had a three times higher uptake rate of nitrate than A. gayanus. We
      hypothesize that A. gayanus stimulates ammonification but inhibits nitrification,
      as was shown to occur in its native range in Africa, and that this modification
      of the soil N cycle is linked to the species' preference for ammonium as an N
      source. This mechanism could result in altered soil N relations and could enhance
      the competitive superiority and persistence of A. gayanus in Australian savannas.

PMID- 19769103
TI  - Habitat conversion, extinction thresholds, and pollination services in
      agroecosystems.
AB  - Parallel declines of wild pollinators and pollinator-dependent plants have raised
      alarms over the loss of pollination services in agroecosystems. A spatially
      explicit approach is needed to develop specific recommendations regarding the
      design of agricultural landscapes to sustain wild pollinator communities and the
      services they provide. I modeled pollination services in agroecosystems using a
      pair of models: a stochastic individual-based simulation model of wild
      pollinators, pollinator-dependent plants, and crop pollination; and a set of
      coupled difference equations designed to capture the nonspatial component of the
      simulation model. Five spatially explicit models of habitat conversion to crops
      were simulated, and results for pollination services were compared. Mean-field
      behavior of the simulation model was in good agreement with analysis of the
      difference equations. A major feature of the models was the presence of a cusp
      leading to loss of stability and extinction of pollinators and pollinator
      dependent plants beyond a critical amount of habitat loss. The addition of pollen
      obtained from crop visitation caused a breakdown of the cusp preventing
      extinction of pollinators, but not of wild pollinator-dependent plants. Spatially
      restricted foraging and dispersal also altered model outcomes relative to mean
      field predictions, in some cases causing extinction under parameter settings that
      would otherwise lead to persistence. Different patterns of habitat conversion to
      crops resulted in different levels of pollination services. Most interesting was
      the finding that optimal pollination services occurred when the size of remnant
      habitat patches was equal to half the mean foraging and dispersal distance of
      pollinators and the spacing between remnant patches was equal to the mean
      foraging and dispersal distance. Conservation of wild pollinators and pollinator
      dependent plants in agroecosystems requires careful attention to thresholds in
      habitat conversion and spatial pattern and scale of remnant habitats.
      Maximization of pollination services was generally incompatible with conservation
      of wild pollinator-dependent plants. My prediction is that pollination services
      will be maximized by providing islands of nesting habitat where interisland
      distance matches mean foraging distances of wild pollinators.

PMID- 19769104
TI  - Climate alters response of an endemic island plant to removal of invasive
      herbivores.
AB  - Islands experience higher rates of species extinction than mainland ecosystems,
      with biological invasions among the leading causes; they also serve as important
      model systems for testing ideas in basic and applied ecology. Invasive removal
      programs on islands are conservation efforts that can also be viewed as powerful
      manipulative experiments, but few data are available to evaluate their effects.
      We collected demographic and herbivore damage data for Castilleja mollis Pennell,
      an endangered plant endemic to Santa Rosa Island, California, over a 12-year
      period before, during, and after the implementation of control for introduced
      cattle, deer, and elk. We used these long-term data to explore mechanisms
      underlying herbivore effects, assess the results of herbivore reduction at the
      scales of both individual plants and populations, and determine how temporal
      variability in herbivory and plant demography influenced responses to herbivore
      removals. For individual plants, herbivore effects mediated by disturbance were
      greater than those of grazing. Deer and elk scraping of the ground substantially
      increased plant mortality and dormancy and reduced flowering and growth. Stem
      damage from browsing did not affect survivorship but significantly reduced plant
      growth and flower production. Herbivore control successfully lowered damage
      rates, which declined steeply between 1997 and 2000 and have remained relatively
      low. Castilleja mollis abundances rose sharply after 1997, suggesting a positive
      effect of herbivore control, but then began to decline steadily again after 2003.
      The recent decline appears to be driven by higher mean growing season
      temperatures; interestingly, not only reductions in scraping damage but a period
      of cooler conditions were significant in explaining increases in C. mollis
      populations between 1997 and 2002. Our results demonstrate strong effects of
      introduced herbivores on both plant demography and population dynamics and show
      that climate-driven variation may counteract and mask positive responses to
      herbivore removal. Regional mean temperatures already have risen significantly
      over the last 50 years, suggesting that climate change could increasingly swamp
      the effects of management targeted at other environmental problems. Similar
      interactions between climate and invasive species will play an even greater role
      in future management, with long-term data sets like this critical to quantifying
      such effects.

PMID- 19769105
TI  - When can efforts to control nuisance and invasive species backfire?
AB  - Population control through harvest has the potential to reduce the abundance of
      nuisance and invasive species. However, demographic structure and density
      dependent processes can confound removal efforts and lead to undesirable
      consequences, such as overcompensation (an increase in abundance in response to
      harvest) and instability (population cycling or chaos). Recent empirical studies
      have demonstrated the potential for increased mortality (such as that caused by
      harvest) to lead to overcompensation and instability in plant, insect, and fish
      populations. We developed a general population model with juvenile and adult
      stages to help determine the conditions under which control harvest efforts can
      produce unintended outcomes. Analytical and simulation analyses of the model
      demonstrated that the potential for overcompensation as a result of harvest was
      significant for species with high fecundity, even when annual stage-specific
      survivorship values were fairly low. Population instability as a result of
      harvest occurred less frequently and was only possible with harvest strategies
      that targeted adults when both fecundity and adult survivorship were high. We
      considered these results in conjunction with current literature on nuisance and
      invasive species to propose general guidelines for assessing the risks associated
      with control harvest based on life history characteristics of target populations.
      Our results suggest that species with high per capita fecundity (over discrete
      breeding periods), short juvenile stages, and fairly constant survivorship rates
      are most likely to respond undesirably to harvest. It is difficult to determine
      the extent to which overcompensation and instability could occur during real
      world removal efforts, and more empirical removal studies should be undertaken to
      evaluate population-level responses to control harvests. Nevertheless, our
      results identify key issues that have been seldom acknowledged and are
      potentially generic across taxa.

PMID- 19769106
TI  - Modeling marine protected areas for threatened eiders in a climatically changing
      Bering Sea.
AB  - Delineating protected areas for sensitive species is a growing challenge as
      changing climate alters the geographic pattern of habitats as well as human
      responses to those shifts. When human impacts are expected within projected
      ranges of threatened species, there is often demand to demarcate the minimum
      habitat required to ensure the species' persistence. Because diminished or wide
      ranging populations may not occupy all viable (and needed) habitat at once, one
      must identify thresholds of resources that will support the species even in
      unoccupied areas. Long-term data on the shifting mosaic of critical resources may
      indicate ranges of future variability. We addressed these issues for the
      Spectacled Eider (Somateria fischeri), a federally threatened species that
      winters in pack ice of the Bering Sea. Changing climate has decreased ice cover
      and severely reduced the eiders' benthic prey and has increased prospects for
      expansion of bottom trawling that may further affect prey communities. To assess
      long-term changes in habitats that will support eiders, we linked data on benthic
      prey, sea ice, and weather from 1970 to 2001 with a spatially explicit simulation
      model of eider energy balance that integrated field, laboratory, and remote
      sensing studies. Areas estimated to have prey densities adequate for eiders in
      1970-1974 did not include most areas that were viable 20 years later (1993-1994).
      Unless the entire area with adequate prey in 1993-1994 had been protected, the
      much reduced viable area in 1999-2001 might well have been excluded. During long
      non-foraging periods (as at night), eiders can save much energy by resting on ice
      vs. floating on water; thus, loss of ice cover in the future might substantially
      decrease the area in which prey densities are adequate to offset the eiders'
      energy needs. For wide-ranging benthivores such as eiders, our results emphasize
      that fixed protected areas based on current conditions can be too small or
      inflexible to subsume long-term shifts in habitat conditions. Better knowledge of
      patterns of natural disturbance experienced by prey communities, and appropriate
      allocation of human disturbance over seasons or years, may yield alternative
      strategies to large-scale closures that may be politically and economically
      problematic.

PMID- 19769107
TI  - Predicting declines in avian species richness under nonrandom patterns of habitat
      loss in a neotropical landscape.
AB  - One of the key concerns in conservation is to document and predict the effects of
      habitat loss on species richness. To do this, the species-area relationship (SAR)
      is frequently used. That relationship assumes random patterns of habitat loss and
      species distributions. In nature, however, species distribution patterns are
      usually nonrandom, influenced by biotic and abiotic factors. Likewise,
      socioeconomic and environmental factors influence habitat loss and are not
      randomly distributed across landscapes. We used a recently developed SAR model
      that accounts for nonrandomness to predict rates of bird species loss in
      fragmented forests of the Panama Canal region, an area that was historically
      covered in forest but now has 53% forest cover. Predicted species loss was higher
      than that predicted by the standard SAR. Furthermore, a species loss threshold
      was evident when remaining forest cover declined by 25%. This level of forest
      cover corresponds to 40% of the historical forest cover, and our model predicts
      rapid species loss past that threshold. This study illustrates the importance of
      considering patterns of species distributions and realistic habitat loss
      scenarios to develop better estimates of losses in species richness. Forecasts of
      tropical biodiversity loss generated from simple species-area relationships may
      underestimate actual losses because nonrandom patterns of species distributions
      and habitat loss are probably not unique to the Panama Canal region.

PMID- 19769108
TI  - Influence of human development and predators on nest survival of tundra birds,
      Arctic Coastal Plain, Alaska.
AB  - Nest predation may influence population dynamics of birds on the Arctic Coastal
      Plain (ACP) of Alaska, USA. Anthropogenic development on the ACP is increasing,
      which may attract nest predators by providing artificial sources of food,
      perches, den sites, and nest sites. Enhanced populations or concentrations of
      human-subsidized predators may reduce nest survival for tundra-nesting birds. In
      this study, we tested the hypothesis that nest survival decreases in proximity to
      human infrastructure. We monitored 1257 nests of 13 shorebird species and 619
      nests of four passerine species at seven sites on the ACP from 2002 to 2005.
      Study sites were chosen to represent a range of distances to infrastructure from
      100 m to 80 km. We used Cox proportional hazards regression models to evaluate
      the effects of background (i.e., natural) factors and infrastructure on nest
      survival. We documented high spatial and temporal variability in nest survival,
      and site and year were both included in the best background model. We did not
      detect an effect of human infrastructure on nest survival for shorebirds as a
      group. In contrast, we found evidence that risk of predation for passerine nests
      increased within 5 km of infrastructure. This finding provides quantitative
      evidence of a relationship between infrastructure and nest survival for breeding
      passerines on the ACP. A posteriori finer-scale analyses (within oil field sites
      and individual species) suggested that Red and Red-necked Phalaropes combined
      (Phalaropus fulicarius, P. lobatus) had lower productivity closer to
      infrastructure and in areas with higher abundance of subsidized predators.
      However, we did not detect such a relationship between infrastructure and nest
      survival for Semipalmated and Pectoral Sandpipers (Calidris pusilla, C.
      melanotos), the two most abundant shorebirds. High variability in environmental
      conditions, nest survival, and predator numbers between sites and years may have
      contributed to these inconsistent results. We recommend targeted management
      actions to minimize anthropogenic effects and suggest new research needed on this
      issue as expanding development is planned for the ACP of Alaska. In particular,
      we recommend research on demography of key predators and their importance with
      respect to nest survival, and experimental studies that better address challenges
      posed by high natural variability.

PMID- 19769109
TI  - Regional differences in the spatial and temporal heterogeneity of oceanographic
      habitat used by Steller sea lions.
AB  - Over the past three decades, the decline and altered spatial distribution of the
      western stock of Steller sea lions (Eumetopias jubatus) in Alaska have been
      attributed to changes in the distribution or abundance of their prey due to the
      cumulative effects of fisheries and environmental perturbations. During this
      period, dietary prey occurrence and diet diversity were related to population
      decline within metapopulation regions of the western stock of Steller sea lions,
      suggesting that environmental conditions may be variable among regions. The
      objective of this study, therefore, was to examine regional differences in the
      spatial and temporal heterogeneity of oceanographic habitat used by Steller sea
      lions within the context of recent measures of diet diversity and population
      trajectories. Habitat use was assessed by deploying satellite-depth recorders and
      satellite relay data loggers on juvenile Steller sea lions (n = 45) over a five
      year period (2000-2004) within four regions of the western stock, including the
      western, central, and eastern Aleutian Islands, and central Gulf of Alaska. Areas
      used by sea lions during summer months (June, July, and August) were demarcated
      using satellite telemetry data and characterized by environmental variables (sea
      surface temperature [SST] and chlorophyll a [chl a]), which possibly serve as
      proxies for environmental processes or prey. Spatial patterns of SST diversity
      and Steller sea lion population trends among regions were fairly consistent with
      trends reported for diet studies, possibly indicating a link between
      environmental diversity, prey diversity, and distribution or abundance of Steller
      sea lions. Overall, maximum spatial heterogeneity coupled with minimal temporal
      variability of SST appeared to be beneficial for Steller sea lions. In contrast,
      these patterns were not consistent for chl a, and there appeared to be an
      ecological threshold. Understanding how Steller sea lions respond to measures of
      environmental heterogeneity will ultimately be useful for implementing ecosystem
      management approaches and developing additional conservation strategies.

PMID- 19769110
TI  - Using telemetry to mitigate the bycatch of long-lived marine vertebrates.
AB  - The unintended bycatch of long-lived marine species in fishing gear is an
      important global conservation issue. One suite of management approaches used to
      address this problem restricts or modifies fishing practices in areas where the
      probability of bycatch is believed to be high. Information on the distribution
      and behavior of the bycaught species is a desirable component of any such scheme,
      but such observations are often lacking. We describe a spatially explicit
      approach that combines data on the distribution of fishing effort and
      observations of the distribution of bycatch species derived from satellite
      telemetry. In a case study, we used a spatially explicit predator-prey model to
      investigate real-time interactions between three species of sea turtles (Caretta
      caretta, Chelonia mydas, and Lepidochelys kempii) and the fall large-mesh gill
      net fishery that targets southern flounder (Paralichthys lethostigma) in Pamlico
      Sound, North Carolina between 2002 and 2004. The model calculates a spatial
      overlap index, thereby allowing us to identify which fishing areas have the
      greatest risk of encountering bycatch. In this study, our telemetry deployments
      (n = 50) were designed specifically to address existing fisheries conservation
      measures in Pamlico Sound intended to reduce sea turtle bycatch. We were able to
      predict the spatial distribution of bycatch and evaluate management measures.
      This approach offers a powerful tool to managers faced with the need to reduce
      bycatch.

PMID- 19769111
TI  - Effects of predator functional diversity on grassland ecosystem function.
AB  - Predator species individually are known to have important effects on plant
      communities and ecosystem functions such as production, decomposition, and
      elemental cycling, the nature of which is determined by a key functional trait,
      predator hunting mode. However, it remains entirely uncertain how predators with
      different hunting modes combine to influence ecosystem function. I report on an
      experiment conducted in a New England grassland ecosystem that quantified the net
      effects of a sit-and-wait and an actively hunting spider species on the plant
      composition and functioning of a New England grassland ecosystem. I manipulated
      predator functional diversity by varying the dominance ratio of the two predator
      species among five treatments using a replacement series design. Experimentation
      revealed that predator functional diversity effects propagated down the live
      plant-based chain to affect the levels of plant diversity, and plant litter
      quality, elemental cycling, and production. Moreover, many of these effects could
      be approximately by the weighted average of the individual predator species
      effects, suggesting that this kind of predator diversity effect on ecosystems is
      not highly nonlinear.

PMID- 19769112
TI  - Climate warming strengthens indirect interactions in an old-field food web.
AB  - Climate change is expected to alter trophic interactions within food chains, but
      predicting the fate of particular species is difficult because the predictions
      hinge on knowing exactly how climate influences direct and indirect interactions.
      We used two complementary approaches to examine how climate change may alter
      trophic interactions within an old-field food web composed of herbaceous plants,
      grasshopper herbivores, and spider predators. We synthesized data spanning 15
      years of experimentation during which interannual mean growing season temperature
      varied by 2 degrees C and precipitation by 2.5 cm. We also manipulated
      temperature within mesocosms to test the affect of temperature on primary
      production and strength of direct and indirect trophic interactions. Both
      approaches produced similar results: plant production was not directly affected
      by temperature or precipitation, but the strength of top-down indirect effects on
      grasses and forbs increased by 30-40% per 1 degrees C. Hence, the net effect of
      climate change was to strengthen top-down control of this terrestrial system.

PMID- 19769113
TI  - Lack of belowground mutualisms hinders Pinaceae invasions.
AB  - Why particular invasions succeed and others fail is not well understood. The role
      of soil biota has been proposed as important. However, the role of mutualists has
      received much less attention than that of pathogens. Here we report that lack of
      adequate ectomycorrhizal fungi hinders invasion by exotic Pinaceae on Isla
      Victoria, Argentina, by reducing both the probability of establishment and growth
      of invading individuals. More than one hundred exotic tree species were
      introduced to this island ca. 80 years ago, but invasive trees are found in high
      densities only in areas adjacent to plantations. With a series of greenhouse and
      field experiments we found lower mycorrhizal colonization levels and few fungal
      species far from original plantings, and key fungal mutualists are confined to
      areas near plantations, probably owing to dispersal limitations. Low inoculum
      levels far from the plantations are retarding the invasion. Our experiments
      indicate that positive interactions belowground can play a key but
      underappreciated role in invasion dynamics.

PMID- 19769114
TI  - Plant interactions are unimportant in a subarctic-alpine plant community.
AB  - We investigated whether plant interaction intensity in a subarctic-alpine meadow
      is important for determining community structure and species abundance. Using two
      common species as phytometers, we measured interaction intensity using a neighbor
      removal approach. Eight biotic and abiotic variables known to influence species
      abundance and community structure were measured, with regression trees used to
      examine how plant interactions and the biotic and abiotic variables were related
      to species evenness, richness, and phytometer spatial cover. A range of
      interactions was present, with both strong competition and facilitation present
      over small-scale abiotic and biotic gradients. Despite the variation in
      interaction intensity, it was generally unrelated to either community structure
      or phytometer cover. In other words, plant interactions were intense in many
      cases but were not important to community structure. This may be due to the
      prevalence of clonal species in this system and the influence of previous year's
      interactions on plant survival and patterns of community structure. These results
      also suggest how conflicting theories of the role of competition in unproductive
      environments may be resolved. Our findings suggest that plant interactions may be
      intense in reducing individual growth, while simultaneously not important in the
      context of community structure. Plant interactions need to be viewed and tested
      relative to other factors and stresses to accurately evaluate their importance in
      plant communities, with continued differentiation between the intensity of plant
      interactions and their relative importance in communities.

PMID- 19769115
TI  - Beyond competition: the stress-gradient hypothesis tested in plant-herbivore
      interactions.
AB  - The stress-gradient hypothesis predicts that interactions among plants are
      context dependent, shifting from facilitation to competition as environmental
      stress decreases. Although restricted to facilitation/competition, the
      mechanistic model behind the hypothesis is easily modified to include other
      negative interactions that are as important as competition in structuring natural
      communities, e.g., herbivory. To evaluate this hypothesis we experimentally
      tested if the balance between the facilitative and trophic effect of an
      intertidal, burrowing, herbivorous crab in marsh plants is context dependent and
      shifts from positive to negative as stress decreases. By sampling salt marshes
      differing in sediment size characteristics, we show that sites with larger
      sediment particle size had less stressful oxygen levels than sites with fine
      sediment particles, and that the level of stress was reduced by the presence of
      crab burrows. We then conducted a factorial experiment manipulating sediment size
      and crab presence. Results show that, by decreasing soil anoxic stress, crabs
      increase plant growth in stressful zones, but their ecological importance as
      herbivores increases in more benign zones. Our findings suggest that the balance
      between positive and negative interactions along stress gradients is more
      important than previously perceived and also applies to facilitation and
      herbivory between animals and plants.

PMID- 19769116
TI  - Long-term persistence of a neotropical ant-plant population in the absence of
      obligate plant-ants.
AB  - Interactions between ants and ant-plants are considered classic examples of
      obligate mutualisms. Previous studies have indicated that for many ant-plants the
      loss of ant colonies results in severe defoliation or mortality. Although
      individual plants can persist for some period of time without their mutualistic
      partners, to date populations of ant-free plants have only been recorded at high
      altitudes or on remote islands where herbivores are also scarce. We studied the
      interaction between ants, herbivores, and the ant-plant Tococa guianensis in the
      Cerrado region of central Brazil. Using a survey conducted across a large
      geographic region, we show that there is interpopulation variation in ant
      occupancy across sites and habitats. At most sites surveyed, plants were
      inhabited by Allomerus octoarticulatus, an obligate plant-ant. Plants with
      obligate ants had significantly lower standing levels of herbivore damage than
      plants with opportunistic ants and plants with no ant occupants. Furthermore,
      experimental removal of A. octoarticulatus resulted in increased levels of damage
      in both young and mature leaves. Despite the protection provided by obligate
      ants, populations of T. guianensis were found to persist without these ants in
      some areas. Plants without A. octoarticulatus had significantly greater leaf
      toughness and trichome density than those with A. octoarticulatus. Furthermore,
      trichome density in plants with A. octoarticulatus increased after ants were
      removed, probably as a response induced by increased levels of herbivore damage.
      To our knowledge, this is the first record of the occurrence of native
      myrmecophyte populations without their mutualistic ants in mainland low-elevation
      sites. Several factors may help to explain the long-term persistence of T.
      guianensis populations without plant-ants in some areas of the Brazilian Cerrado,
      including its potential for induced morphological defenses against insect
      herbivores and selection for increased levels of constitutive defenses. In
      addition, T. guianensis may be under lower herbivore pressure in the sites we
      studied than in other parts of its range because existing populations were small,
      isolated, and some were very close to the edge of this species' distribution.

PMID- 19769117
TI  - Quantitative synthesis of context dependency in ant-plant protection mutualisms.
AB  - Context dependency, variation in the outcome of species interactions with biotic
      and abiotic conditions, is increasingly considered ubiquitous among mutualisms.
      Despite several qualitative reviews of many individual empirical studies, there
      has been little quantitative synthesis examining the generality of context
      dependency, or conditions that may promote it. We conducted a meta-analysis of
      ant-plant protection mutualisms to examine the generality of context-dependent
      effects of ants on herbivory and plant performance (growth, reproduction). Our
      results show that ant effects on plants are not generally context dependent, but
      instead are routinely positive and rarely neutral, as overall effect sizes of
      ants in reducing herbivory and increasing plant performance were positive and
      significantly greater than 0. The magnitude of these positive effects did vary,
      however. Variation in plant performance was not explained by the type of biotic
      or abiotic factor examined, including plant rewards (extrafloral nectar, food
      bodies, domatia), ant species richness, plant growth form, or latitude. With the
      exception of plant growth form, these factors did contribute to the effects of
      ants in reducing herbivory. Reductions in herbivory were greater for plants with
      than without domatia, and greatest for plants with both domatia and food bodies.
      Effect sizes of ants in reducing herbivory decreased, but remained positive, with
      latitude and ant species richness. Effect sizes in reducing herbivory were
      greater in tropical vs. temperate systems. Although ant-plant interactions have
      been pivotal in the study of context dependency of mutualisms, our results, along
      with other recent meta-analyses, indicate that context dependency may not be a
      general feature of mutualistic interactions. Rather, ant-plant protection
      mutualisms appear to be routinely positive for plants, and only occasionally
      neutral.

PMID- 19769118
TI  - Cardenolides, induced responses, and interactions between above- and belowground
      herbivores of milkweed (Asclepias spp.).
AB  - Theory has long predicted allocation patterns for plant defense against
      herbivory, but only recently have both above- and belowground plant defenses been
      considered simultaneously. Milkweeds in the genus Asclepias are a classic
      chemically defended clade of plants with toxic cardenolides (cardiac glycosides)
      and pressurized latex employed as anti-herbivore weapons. Here we combine a
      comparative approach to investigate broadscale patterns in allocation to root vs.
      shoot defenses across species with a species-specific experimental approach to
      identify the consequences of defense allocational shifts on a specialist
      herbivore. Our results show phylogenetic conservatism for inducibility of shoot
      cardenolides by an aboveground herbivore, with only four closely related tropical
      species showing significant induction; the eight temperate species examined were
      not inducible. Allocation to root and shoot cardenolides was positively
      correlated across species, and this relationship was maintained after accounting
      for phylogenetic nonindependence. In contrast to long-standing theoretical
      predictions, we found no evidence for a trade-off between constitutive and
      induced cardenolides; indeed the two were positively correlated across species in
      both roots and shoots. Finally, specialist root and shoot herbivores of common
      milkweed (A. syriaca) had opposing effects on latex production, and these effects
      had consequences for caterpillar growth consistent with latex providing
      resistance. Although cardenolides were not affected by our treatments, A. syriaca
      allocated 40% more cardenolides to shoots over roots. We conclude that
      constitutive and inducible defenses are not trading off across plant species, and
      shoots of Asclepias are more inducible than roots. Phylogenetic conservatism
      cannot explain the observed patterns of cardenolide levels across species, but
      inducibility per se was conserved in a tropical clade. Finally, given that above-
      and belowground herbivores can systemically alter the defensive phenotype of
      plants, we concur with recent calls for a whole-plant perspective in testing
      models of plant defense allocation.

PMID- 19769119
TI  - Interpopulation divergence in competitive interactions of the mosquito Aedes
      albopictus.
AB  - Geographic variation in species interactions can have major effects on
      distributions. Effects of such variation can be particularly evident for invasive
      species, in which variation in competitive ability can influence invasive success
      and impacts. We tested the hypothesis that coexistence or exclusion of the
      resident mosquito Aedes aegypti results from variation among local populations of
      the invasive Aedes albopictus in competitive interactions with A. aegypti. We
      also examined the role of variation in fecundity-size relationships in these
      competitive interactions. We compared competitive abilities of nine North
      American populations of A. albopictus, three populations from each of three site
      types: extinction of A. aegypti following A. albopictus invasion, coexistence
      following A. albopictus invasion, and A. albopictus allopatric to A. aegypti.
      Competition among larvae from each A. albopictus population and a single A.
      aegypti population was tested in laboratory microcosms in a response surface
      design. We found interpopulation differences in competitive ability of A.
      albopictus, but no strong patterns among site types. Extinction sites had steeper
      average fecundity-size relationships than coexistence sites and allopatric sites,
      but this did not translate into superior population performance. Certain
      individual A. albopictus populations had exceptionally large competitive effects
      on A. aegypti or poor competitive responses to competition from A. aegypti, but
      competitive effect and response were not correlated. These results suggest that
      interpopulation variation in the competitive ability of A. albopictus may only
      partly explain the geographic pattern of coexistence with or extinction of A.
      aegypti. Environmental differences among regions may affect the competitive
      ability of A. albopictus and influence its invasion success and impact.

PMID- 19769120
TI  - Random, top-down, or bottom-up coexistence of parasites: malaria population
      dynamics in multi-parasitic settings.
AB  - Epidemiological models concerned with the control of malaria using interventions
      such as bed nets and vaccines increasingly incorporate realistic aspects of
      malaria biology. The increasing complexity of these models limits their ability
      to abstract ecological processes and to address questions on the regulation of
      population dynamics using time-series data, particularly in regards to
      interactions between different pathogens and the regulatory role of innate
      (bottom-up) and acquired (top-down) immunity. We use a theoretical framework to
      test hypotheses on the importance of population-level immunity and parasite
      abundance in regulating the population dynamics of malaria. We use qualitative
      loop analyses to examine the sign of the interaction between Plasmodium
      falciparum and P. vivax at the population level, and we discuss implications of
      this sign for the within-host regulation of parasites. Our analyses of monthly
      malaria time-series data from the island of Espirito Santo, Vanuatu (1983-1997),
      show that the dynamics of P. falciparum are not sensitive to P. vivax, whereas
      infections by the latter increase in response to those of the former. These
      results support a differential use of resources inside the hosts, a resource
      consumer interaction between hosts and their immune system, and within-host
      regulation of parasites. Finally, our results emphasize the need to better
      understand factors regulating malaria dynamics before developing control
      strategies and call for the use of control strategies directed at the
      interruption of transmission, such as vector control and the use of bed nets.

PMID- 19769121
TI  - Press perturbations and indirect effects in real food webs.
AB  - The prediction of the effects of disturbances in natural systems is limited by
      the general lack of knowledge on the strength of species interactions, i.e., the
      effect of one species on the population growth rate of another, and by the
      uncertainty of the effects that may be manifested via indirect pathways within
      the food web. Here we explored the consequences of changes in species populations
      for the remaining species within nine exceptionally well-characterized empirical
      food webs, for which, unlike the vast majority of other published webs, feeding
      links have been fully quantified. Using the inverse of the Jacobian matrix, we
      found that perturbations to species with few connections have larger net effects
      (considering both direct and indirect pathways between two species) on the rest
      of the food web than do disturbances to species that are highly connected. For
      40% of predator-prey links, predators had positive net effects on prey
      populations, due to the predominance of indirect interactions. Our results
      highlight the fundamental, but often counterintuitive, role of indirect effects
      for the maintenance of food web complexity and biodiversity.

PMID- 19769122
TI  - Intraguild predation in a structured habitat: distinguishing multiple-predator
      effects from competitor effects.
AB  - The ability to forecast community dynamics requires, among other things, an
      understanding of indirect effects and nonlinearities in webs of interacting
      species, together with knowledge of how habitat structure mediates interactions.
      We explored these aspects for a coral reef system in Moorea, French Polynesia,
      involving intraguild predation where the shared damselfish prey (juvenile
      yellowtail dascyllus Dascyllusflavicaudus) and two species of intraguild (IG)
      prey (the ambush predators arc-eye hawkfish Paracirrhites arcatus and red-spotted
      coral crab Trapezia rufopunctata) shelter together in branching Pocilloporid
      corals for protection from mobile IG predators. Field experiments revealed that
      both IG prey had strong adverse effects on survivorship of juvenile damselfish,
      but that the dominant underlying process was competition for enemy-free space and
      not direct consumption. In this case, the combined effect of hawkfish and crabs
      did not result in either risk enhancement or risk reduction for the damselfish.
      Similarly, the combined influence of IG predators and IG prey on the shared prey
      also was indistinguishable from that expected from their independent effects.
      Habitat structure weakened the IG-prey-IG-predator interaction; IG prey were much
      stronger space competitors with damselfish than resource competitors with IG
      predators. As a consequence, there was not a trophic cascade where damselfish
      benefited by the adverse effect of IG predators on hawkfish or coral crabs. These
      results highlight the manner by which habitat structure can mediate species
      interactions and emphasize the need to understand the underlying mechanisms.

PMID- 19769123
TI  - Trait-based assembly and phylogenetic structure in northeast Pacific rockfish
      assemblages.
AB  - If natural communities are assembled according to deterministic rules, coexisting
      species will represent a nonrandom subset of the potential species pool. We
      tested for signatures of assembly rules in the distribution of species' traits in
      Pacific rockfish (Sebastes spp.) assemblages. We used morphology, dietary niche
      (estimated with stable nitrogen isotopes), and distribution data to identify
      traits that relate to local-scale resource use (the alpha-niche) and to
      environmental gradients (the beta-niche). We showed that gill raker morphology
      was related to trophic position (an alpha-niche axis), while relative eye size
      was associated with depth habitat (a beta-niche axis). We therefore hypothesized
      that, within assemblages of coexisting rockfish species, the gill raker trait
      would be overdispersed (evenly spaced) due to limiting similarity, while relative
      eye size would be clustered due to environmental filtering. We examined the
      evolutionary relatedness of coexisting species to ask whether phylogenetic
      community structure and trait distributions gave similar indications about the
      roles of assembly processes. We tested the trait distributions and phylogenetic
      structure of 30 published rockfish assemblages against a null model of random
      community assembly. As predicted, the gill raker trait tended to be more evenly
      spaced than expected by chance, as did overall body size, while relative eye size
      was more clustered than expected. Phylogenetic community structure appeared to
      reflect historical dispersal and speciation and did not provide consistent
      support for assembly rules. Our results indicate that rockfish community assembly
      is nonrandom with regard to species' traits and show how distinguishing traits
      related to the alpha- and beta-niches and incorporating functional morphology can
      provide for powerful tests of assembly rules.

PMID- 19769124
TI  - Wolf presence and increased willow consumption by Yellowstone elk: implications
      for trophic cascades.
AB  - Recent increases in the height and growth ring width of willow (Salix spp.) and
      other woody plants in the Greater Yellowstone Ecosystem (GYE) have been
      attributed to a behaviorally mediated trophic cascade from wolves (Canis lupus)
      to elk (Cervus elaphus) to willows. This hypothesis predicts that individual elk
      consume less willow in response to the presence of wolves, but this prediction
      has not been directly tested with data from elk. We collected 727 fecal samples
      from elk in the Gallatin Canyon portion of the GYE over three winters and used
      microhistological methods to quantify the proportion of willow in each sample. We
      then tested the effect of wolf presence on willow consumption by elk, controlling
      for the effects of snow conditions, sex, and habitat type. During the period of
      study, 8-17 wolves occupied the study area, and wolves were locally present on
      49% of 260 sampling days, stratified at two-week intervals across three
      drainages. Over the three years combined, willow consumption was related to snow
      conditions, wolf presence, and a wolf X sex interaction. As expected, willow
      consumption increased with deeper and less penetrable snow, and this effect was
      strong. Contrary to expectation, willow consumption increased in the presence of
      wolves. As with other aspects of antipredator behavior, wolves had different
      effects on willow consumption by males and females. Finally, we aggregated the
      data to estimate winter-long mean willow consumption within each drainage; at
      this broader scale, willow consumption again increased as predation risk
      increased. In summary, willow consumption was more strongly affected by snow
      conditions than by the presence of wolves. Interactions between elk and willow
      were affected by wolves, but not as predicted by the hypothesis that wolf
      presence favors willow release through a reduction in the selection of willow by
      individual elk. If a trophic cascade is operating, our results suggest that a
      decline in the size of the elk population (to roughly one-half its size
      immediately prior to wolf recovery) may be more important than changes in the
      willow consumption of individual elk. Finally, reduced grazing of herbaceous
      vegetation may be equally important for vegetation dynamics.

PMID- 19769126
TI  - Group-size-mediated habitat selection and group fusion-fission dynamics of bison
      under predation risk.
AB  - For gregarious animals the cost-benefit trade-offs that drive habitat selection
      may vary dynamically with group size, which plays an important role in foraging
      and predator avoidance strategies. We examined how habitat selection by bison
      (Bison bison) varied as a function of group size and interpreted these patterns
      by testing whether habitat selection was more strongly driven by the competing
      demands of forage intake vs. predator avoidance behavior. We developed an
      analytical framework that integrated group size into resource selection functions
      (RSFs). These group-size-dependent RSFs were based on a matched case-control
      design and were estimated using conditional logistic regression (mixed and
      population-averaged models). Fitting RSF models to bison revealed that bison
      groups responded to multiple aspects of landscape heterogeneity and that
      selection varied seasonally and as a function of group size. For example, roads
      were selected in summer, but not in winter. Bison groups avoided areas of high
      snow water equivalent in winter. They selected areas composed of a large
      proportion of meadow area within a 700-m radius, and within those areas, bison
      selected meadows. Importantly, the strength of selection for meadows varied as a
      function of group size, with stronger selection being observed in larger groups.
      Hence the bison-habitat relationship depended in part on the dynamics of group
      formation and division. Group formation was most likely in meadows. In contrast,
      risk of group fission increased when bison moved into the forest and was higher
      during the time of day when movements are generally longer and more variable
      among individuals. We also found that stronger selection for meadows by large
      rather than small bison groups was caused by longer residence time in individual
      meadows by larger groups and that departure from meadows appears unlikely to
      result from a depression in food intake rate. These group-size-dependent patterns
      were consistent with the hypothesis that avoidance of predation risk is the
      strongest driver of habitat selection.

PMID- 19769125
TI  - Methods for assessing movement path recursion with application to African buffalo
      in South Africa.
AB  - Recent developments of automated methods for monitoring animal movement, e.g.,
      global positioning systems (GPS) technology, yield high-resolution spatiotemporal
      data. To gain insights into the processes creating movement patterns, we present
      two new techniques for extracting information from these data on repeated visits
      to a particular site or patch ("recursions"). Identification of such patches and
      quantification of recursion pathways, when combined with patch-related ecological
      data, should contribute to our understanding of the habitat requirements of large
      herbivores, of factors governing their space-use patterns, and their interactions
      with the ecosystem. We begin by presenting output from a simple spatial model
      that simulates movements of large-herbivore groups based on minimal parameters:
      resource availability and rates of resource recovery after a local depletion. We
      then present the details of our new techniques of analyses (recursion analysis
      and circle analysis) and apply them to data generated by our model, as well as
      two sets of empirical data on movements of African buffalo (Syncerus caffer): the
      first collected in Klaserie Private Nature Reserve and the second in Kruger
      National Park, South Africa. Our recursion analyses of model outputs provide us
      with a basis for inferring aspects of the processes governing the production of
      buffalo recursion patterns, particularly the potential influence of resource
      recovery rate. Although the focus of our simulations was a comparison of movement
      patterns produced by different resource recovery rates, we conclude our paper
      with a comprehensive discussion of how recursion analyses can be used when
      appropriate ecological data are available to elucidate various factors
      influencing movement. Inter alia, these include the various limiting and
      preferred resources, parasites, and topographical and landscape factors.

PMID- 19769127
TI  - Consequences of recruitment decisions and heterogeneity on age-specific breeding
      success in a long-lived seabird.
AB  - An individual's age at first reproduction and investment in successive
      reproductive attempts are involved in mechanisms that can impede somatic repair,
      resulting in a decline in reproductive abilities with age (reproductive
      senescence). We used long-term data from the Black-legged Kittiwake, a long-lived
      seabird, to address the relationship between recruitment age, age-specific
      breeding success (BS), and reproductive senescence, while accounting for breeding
      experience and temporal variation in BS. We first detected late-life improvement
      in BS across all recruitment groups, which we recognized as "within-generation
      selection" or the selective disappearance of "frail" phenotypes. When such
      heterogeneity was accurately accounted for, we showed that all individuals
      suffered reproductive senescence. We first highlighted how different combinations
      of pre- and post-recruitment experience across recruitment groups resulted in
      maximal BS at intermediate ages. BS increased in early recruits as they gained
      post-recruitment experience, whereas late recruits gained pre-recruitment
      experience that led to high BS at recruitment. Only individuals recruiting at
      intermediate ages balanced their pre- and post-recruitment experience. Consistent
      with the "cumulative reproductive cost hypothesis," we also observed a faster
      decline in BS in early recruits at advanced ages, whereas individuals delaying
      recruitment experienced the slowest decline in BS with age. Early recruits,
      however, reached the highest levels of BS at intermediate ages, sensus stricto
      (10-13 years old), whereas individuals delaying recruitment experienced the
      lowest at similar ages. These divergent trajectories may reflect a "delayed trade
      off" balancing a maximization of midlife BS against reproductive senescence at
      advanced ages. Additionally, annual variation in BS had a greater effect on
      individuals early in life, suggesting that experienced individuals were able to
      buffer out the effects of temporal variation on BS, which can ultimately improve
      fitness in stochastic environments. Our findings stress that (1) both observed
      and unobserved heterogeneity are important in detecting within-individual
      senescence, and (2) short-term trade-offs may be rare in long-lived species;
      thus, cumulated reproductive costs should be invoked as an alternative mechanism
      underlying reproductive senescence.

PMID- 19769128
TI  - A reanalysis of competing hypotheses for the spread of the California sea otter.
AB  - From 1938 to 1972, the range of California sea otters (Enhydra lutris nereis)
      expanded with the northern and southern fronts spreading at rates of
      approximately 1.4 km/yr and 3.1 km/yr, respectively. J. A. Lubina and S. A. Levin
      proposed the following three factors to explain the large disparity in spread
      rates: (1) regional differences in dispersal; (2) regional differences in
      population growth; and (3) advection due to the known presence of a southerly
      flowing offshore current. While Lubina and Levin used a reaction-diffusion
      framework to argue for large differences in dispersal, our approach uses a stage
      structured integrodifference matrix model to show that relatively minor
      differences in survival provide a more parsimonious explanation for the disparity
      in spread rates; especially if the survival rates between the northern and
      southern groups differ in more than one life stage. The argument is made that
      many of the present estimates for otter survival rates span intervals wide enough
      to explain the different spread rates--even more so in the likely case that
      advection plays at least a minor role in otter movement.

PMID- 19769129
TI  - Repeatability in lactation performance and the consequences for maternal
      reproductive success in gray seals.
AB  - In mammals, the most significant maternal effect on offspring growth during
      lactation is the ability of females to efficiently transfer milk energy to their
      neonates. However, despite the importance of the transfer of milk energy to both
      maternal and offspring fitness, nothing is known about the extent to which
      variation among females may be attributed to differences in individual quality or
      environmental variation in natural populations. We measured repeatability over
      multiple lactation periods in components of lactation performance in free
      ranging, multiparous gray seal (Halichoerus grypus) females to examine to what
      extent variation among females in pup weaning mass may be attributed to inherent
      differences in their physiological capacity to deliver milk energy. Levels of
      repeatability were high for milk composition (r = 0.38-0.50), daily milk output
      (r = 0.46), and the duration of lactation (r = 0.57), demonstrating that there
      are consistent differences among females in these characters across lactations
      and that the overall capacity of gray seal females to deliver milk energy to
      their pups is characteristic of individuals. The repeatability in pup weaning
      mass (r = 0.48) was consistent with the values for the components of total milk
      energy output and suggests that, over a large proportion of their reproductive
      life, individual gray seal females will consistently wean pups with greater or
      lesser probabilities of survival. Our results suggest that inherent differences
      among females in their physiological capacity to deliver milk energy may be an
      important component of variation in individual quality and, thus, lifetime
      reproductive success in mammals. High levels of repeatability also suggest that
      components of milk energy transfer may have a significant heritable genetic
      basis.

PMID- 19769130
TI  - Compensatory responses to food restriction in juvenile green turtles (Chelonia
      mydas).
AB  - The purpose of this study was to assess the compensatory responses to food
      restriction and subsequent increased food availability in juvenile green turtles
      (Chelonia mydas). Turtles were fed an ad libitum ration for 12 weeks (AL), a
      restricted ration for 12 weeks (R), or a restricted ration for 5 weeks and an ad
      libitum ration for 7 weeks (R-AL). Analysis of covariance was used to test the
      relationships between (1) growth and body size, (2) intake and body size, and (3)
      growth and intake for each of the three treatment groups. Body composition of
      turtles in each group was also evaluated at the beginning of the study and after
      weeks 5 and 12. After the switch to ad libitum feeding, R-AL turtles consumed
      comparable amounts of food and grew faster than AL turtles on a size-adjusted
      basis, but mean body sizes did not converge, although the overlap in their size
      ranges increased with time. The R-AL turtles also converted food to growth more
      efficiently and allocated proportionally more nutrients to protein accretion,
      thereby restoring body composition (except mineral content) to AL levels by the
      end of the study. Thus, accelerated size-specific growth without hyperphagia
      restored body condition but not size. These results indicate that (1) intake in
      juvenile green turtles is maximal when food is readily available and cannot be
      increased to compensate for a previous period of food limitation, (2) growth
      rates of ad libitum-fed turtles are only mildly plastic in response to past
      nutritional history, and (3) priority rules for nutrient allocation favor the
      attainment of an optimal condition rather than an optimal size. Nutritional
      setbacks experienced during the vulnerable juvenile stage could therefore have
      long-lasting consequences for wild turtles in terms of size-specific mortality
      risk, but these risks may be mitigated by the potential benefits of maintaining
      sufficient body stores.

PMID- 19769131
TI  - Salt marsh ecosystem biogeochemical responses to nutrient enrichment: a paired
      15N tracer study.
AB  - We compared processing and fate of dissolved NO3- in two New England salt marsh
      ecosystems, one receiving natural flood tide concentrations of approximately 1-4
      micromol NO3-/ L and the other receiving experimentally fertilized flood tides
      containing approximately 70-100 micromol NO3-/ L. We conducted simultaneous 15NO3
      (isotope) tracer additions from 23 to 28 July 2005 in the reference (8.4 ha) and
      fertilized (12.4 ha) systems to compare N dynamics and fate. Two full tidal
      cycles were intensively studied during the paired tracer additions. Resulting
      mass balances showed that essentially 100% (0.48-0.61 mol NO3-N.ha(-1).h(-1)) of
      incoming NO3- was assimilated, dissimilated, sorbed, or sedimented (processed)
      within a few hours in the reference system when NO3- concentrations were 1.3-1.8
      micromol/L. In contrast, only 50-60% of incoming NO3- was processed in the
      fertilized system when NO3- concentrations were 84-96 micromol/L; the remainder
      was exported in ebb tidewater. Gross NO3- processing was approximately 40 times
      higher in the fertilized system at 19.34-24.67 mol NO3-N.ha(-1).h(-1).
      Dissimilatory nitrate reduction to ammonium was evident in both systems during
      the first 48 h of the tracer additions but <1% of incoming 15NO3- was exported as
      15NH4+. Nitrification rates calculated by 15NO3- dilution were 6.05 and 4.46
      mol.ha(-1).h(-1) in the fertilized system but could not be accurately calculated
      in the reference system due to rapid (<4 h) NO3- turnover. Over the five-day
      paired tracer addition, sediments sequestered a small fraction of incoming NO3-,
      although the efficiency of sequestration was 3.8% in the reference system and
      0.7% in the fertilized system. Gross sediment N sequestration rates were similar
      at 13.5 and 12.6 mol.ha(-1).d(-1), respectively. Macrophyte NO3- uptake
      efficiency, based on tracer incorporation in aboveground tissues, was
      considerably higher in the reference system (16.8%) than the fertilized system
      (2.6%), although bulk uptake of NO3- by plants was lower in the reference system
      (1.75 mol NO3-.ha(-1).d(-1)) than the fertilized system (approximately 10 mol NO3
      .ha(-1).d(-1)). Nitrogen processing efficiency decreased with NO3- load in all
      pools, suggesting that the nutrient processing capacity of the marsh ecosystem
      was exceeded in the fertilized marsh.

PMID- 19769132
TI  - Biotic and abiotic controls on diurnal fluctuations in labile soil phosphorus of
      a wet tropical forest.
AB  - The productivity of many tropical wet forests is generally limited by
      bioavailable phosphorus (P). Microbial activity is a key regulator of P
      availability in that it determines both the supply of P through organic matter
      decomposition and the depletion of bioavailable P through microbial uptake. Both
      microbial uptake and mineralization occur rapidly, and their net effect on P
      availability varies with soil moisture, temperature, and soil organic matter
      quantity and quality. Exploring the mechanisms driving P availability at fine
      temporal scales can provide insight into the coupling of carbon, water, and
      nutrient cycles, and ultimately, the response of tropical forests to climate
      change. Despite the recognized importance of P cycling to the dynamics of wet
      tropical forests and their potential sensitivity to short-term fluctuations in
      bioavailable P, the diurnal pattern of P remains poorly understood. This study
      quantifies diurnal fluctuations in labile soil P and evaluates the importance of
      biotic and abiotic factors in driving these patterns. To this end, measurements
      of labile P were made every other hour in a Costa Rican wet tropical forest
      oxisol. Spatial and temporal variation in Bray-extractable P were investigated in
      relation to ecosystem carbon flux, soil CO2 efflux, soil moisture, soil
      temperature, solar radiation, and sap-flow velocity. Spatially averaged bi-hourly
      (every two hours) labile P ranged from 0.88 to 2.48 microg/g across days. The
      amplitude in labile P throughout the day was 0.61-0.82 microg/g (41-54% of mean P
      concentrations) and was characterized by a bimodal pattern with a decrease at
      midday. Labile P increased with soil CO2 efflux and soil temperature and declined
      with increasing sap flow and solar radiation. Together, soil CO2 efflux, soil
      temperature, and sap flow explained 86% of variation in labile P.

PMID- 19769133
TI  - Nutrient enrichment alters storage and fluxes of detritus in a headwater stream
      ecosystem.
AB  - Responses of detrital pathways to nutrients may differ fundamentally from
      pathways involving living plants: basal carbon resources can potentially decrease
      rather than increase with nutrient enrichment. Despite the potential for
      nutrients to accelerate heterotrophic processes and fluxes of detritus, few
      studies have examined detritus-nutrient dynamics at whole-ecosystem scales. We
      quantified organic matter (OM) budgets over three consecutive years in two
      detritus-based Appalachian (U.S.A.) streams. After the first year, we began
      enriching one stream with low-level nitrogen and phosphorus inputs. Subsequent
      effects of nutrients on outputs of different OM compartments were determined
      using randomized intervention analysis. Nutrient addition did not affect
      dissolved or coarse particulate OM export but had dramatic effects on fine
      particulate OM (FPOM) export at all discharges relative to the reference stream.
      After two years of enrichment, FPOM export was 340% higher in the treatment
      stream but had decreased by 36% in the reference stream relative to pretreatment
      export. Ecosystem respiration, the dominant carbon output in these systems, also
      increased in the treatment stream relative to the reference, but these changes
      were smaller in magnitude than those in FPOM export. Nutrient enrichment
      accelerated rates of OM processing, transformation, and export, potentially
      altering food-web dynamics and ecosystem stability in the long term. The results
      of our large-scale manipulation of a detrital ecosystem parallel those from
      analogous studies of soils, in which net loss of organic carbon has often been
      shown to result from experimental nutrient addition at the plot scale. Streams
      are useful model systems in which to test the effects of nutrients on ecosystem
      scale detrital dynamics because they allow both the tracking of OM conversion
      along longitudinal continua and the integrated measurement of fluxes of
      transformed material through downstream sites.

PMID- 19769134
TI  - Community-level consequences of mycorrhizae depend on phosphorus availability.
AB  - In grasslands, arbuscular mycorrhizal fungi (AMF) mediate plant diversity;
      whether AMF increase or decrease diversity depends on the relative mycotrophy in
      dominant vs. subordinate plants. In this study we investigated whether soil
      nutrient levels also influence the ability of AMF to mediate plant species
      coexistence. First, we developed a conceptual model that predicts the influence
      of AMF on diversity along a soil nutrient gradient for plant communities
      dominated by mycotrophic and non-mycotrophic species. To test these predictions,
      we manipulated phosphorus to create a soil nutrient gradient for mesocosm
      communities composed of native prairie grasses and then compared community
      properties for mesocosms with and without AMF. We found that, where P was
      limiting, AMF increased plant diversity and productivity, and also altered
      community structure; however, at high P, AMF had little influence on aboveground
      communities. Compositional differences among treatments were due largely to a
      trade-off in the relative abundance of C3 vs. C4 spes. Our study emphasizes how
      environmental constraints on mutualisms may govern community- and ecosystem-level
      properties.

PMID- 19769135
TI  - Patch size effects on plant species decline in an experimentally fragmented
      landscape.
AB  - Understanding local and global extinction is a fundamental objective of both
      basic and applied ecology. Island biogeography theory (IBT) and succession theory
      provide frameworks for understanding extinction in changing landscapes. We
      explore the relative contribution of fragment size vs. succession on species'
      declines by examining distributions of abundances for 18 plant species declining
      over time in an experimentally fragmented landscape in northeast Kansas, U.S.A.
      If patch size effects dominate, early-successional species should persist longer
      on large patches, but if successional processes dominate, the reverse should
      hold, because in our system woody plant colonization is accelerated on large
      patches. To compare the patterns in abundance among patch sizes, we characterize
      joint shifts in local abundance and occupancy with a new metric: rank occupancy
      abundance profiles (ROAPs). As succession progressed, statistically significant
      patch size effects emerged for 11 of 18 species. More early-successional species
      persisted longer on large patches, despite the fact that woody encroachment
      (succession) progressed faster in these patches. Clonal perennial species
      persisted longer on large patches compared to small patches. All species that
      persisted longer on small patches were annuals that recruit from the seed bank
      each year. The degree to which species declined in occupancy vs. abundance varied
      dramatically among species: some species declined first in occupancy, others
      remained widespread or even expanded their distribution, even as they declined in
      local abundance. Consequently, species exhibited various types of rarity as
      succession progressed. Understanding the effect of fragmentation on extinction
      trajectories requires a species-by-species approach encompassing both occupancy
      and local abundance. We propose that ROAPs provide a useful tool for comparing
      the distribution of local abundances among landscape types, years, and species.

PMID- 19769136
TI  - Extra-regional residence time as a correlate of plant invasiveness: European
      archaeophytes in North America.
AB  - Human activities have degraded biogeographical barriers to dispersal resulting in
      the spread and naturalization of increasing numbers of nonnative invasive
      species. One correlate of invasiveness within a region is residence time or time
      since introduction. Plant species that were introduced into Europe prior to AD
      1500 (European archaeophytes) that were subsequently introduced into North
      America provide a unique opportunity to examine the effect of extra-regional
      residence time (i.e., residence time that occurred in a nonnative region before a
      species was introduced into a new region). Here, we examine how nonnative species
      with extensive extra-regional residence times have affected beta diversity among
      states in the contiguous United States of America based on an analysis of
      occupancy and distance decay of similarity. State floras contained an average of
      3106 +/- 922 species (mean +/- SD) with 2318 +/- 757 species classified as
      native, 180 +/- 43 species as European archaeophyte, and 608 -236 species as
      other exotic with no European archaeophyte association. For European
      archaeophytes, 42% were identified as noxious weeds in the United States with 8%
      identified as agricultural and 14% as natural-area weeds (20%, 2%, and 13% for
      other exotics, respectively). In strong contrast to natives and other exotics,
      European archaeophytes were more widespread and presented weaker distance-decay
      patterns. Thus, European archaeophytes were more likely to become noxious weeds,
      particularly within agricultural areas, and were associated with significant
      losses in beta diversity. We suggest that this outcome is a consequence of extra
      regional residence time, which allowed for the selection of species or the
      evolution of traits that favored the colonization of arable habitats associated
      with early agricultural activities in Europe, habitats that are widespread,
      resource rich, and uniformly distributed in the United States. Our findings
      suggest that a long-term trajectory can be established, with residence time in
      one region building biological and geographical potential, often in direct
      association with anthropogenic activities, for invasions in new regions. When
      predicting or managing for potential invaders within a region, identifying extra
      regional residence time and its consequences is critical when assessing a
      species' long-term invasive potential.

PMID- 19769137
TI  - Two-phase functional redundancy in plant communities along a grazing gradient in
      Mongolian rangelands.
AB  - The concept of functional redundancy is at the core of theory relating changes in
      ecosystem functioning to species loss. However, few empirical studies have
      investigated the strength and form of the relationship between species and
      functional diversity (i.e., the presence of functional redundancy in ecological
      communities) in this context. In particular, we know little about how local
      extinctions in real communities might impact functional diversity. Here, we
      examined the relationship between species and functional diversity in plant
      communities along a grazing gradient across Mongolian rangeland ecosystems. We
      applied a recently described measure of functional diversity that incorporates
      species' dissimilarities defined from plant functional traits and tested several
      hypothesized forms of the relationship between species and functional diversity
      using linear and nonlinear modeling techniques. We found a significant sigmoid
      logistic relationship between species richness and functional diversity in
      relatively benign environmental conditions. This indicates high functional
      redundancy at low levels of species richness followed by a rapid increase at
      intermediate levels, until functional diversity reaches an asymptote at high
      levels (i.e., two-phase functional redundancy). In contrast, we generally
      observed a positive linear relationship between these parameters in relatively
      harsh environmental conditions, indicating low functional redundancy. Observed
      functional redundancy probably resulted from two factors, intrinsic redundancy in
      species' functional traits and extrinsic redundancy caused by nonrandom
      compositional change that is nonrandom with respect to functional traits. Lack of
      either intrinsic or extrinsic redundancy may result in low functional redundancy.
      Two-phase functional redundancy suggests that functional traits are abruptly lost
      from a community below a certain level of species richness, and a community then
      shifts into a contrasting state that has a few limited functional groups
      characterized by disturbance-resistant traits, as a consequence of disturbances
      such as livestock grazing. This study represents a major step forward in
      predicting the consequences of livestock grazing on the functioning of Mongolian
      rangeland ecosystems.

PMID- 19769138
TI  - Impact of three global change drivers on a Mediterranean shrub.
AB  - Global change is not restricted to climate change, and plant species generally
      face multiple human-driven disturbances constraining their viability. Most
      importantly, interactions among these drivers frequently generate nonadditive
      effects that cannot be predicted based on single-factor studies. Our goal was to
      assess the joint effects of three global change drivers that are especially
      relevant in Mediterranean ecosystems, namely, fragmentation, reduced habitat
      quality, and climate change on Centaurea hyssopifolia, a gypsum specialist plant.
      We carried out a two-year study (2005-2006) in natural populations of this plant
      in large (>11 ha) and small (< 1.5 ha) fragments. Within each fragment, we
      identified areas of contrasting habitat quality as revealed by plant cover and
      nutrient content, and within each combination of habitat quality and fragment
      size we performed a rainfall manipulation experiment simulating the most likely
      future climate scenario for the region. Survival, growth, phenology, and
      reproductive success of selected plants were monitored. The three drivers
      profoundly affected responses of Centaurea hyssopifolia in both study years,
      phenology being mainly affected by changes in habitat quality and reductions in
      rainfall and reproductive traits being mainly affected by fragmentation. Plants
      in sites of poor habitat quality and plants in the dry treatment advanced most of
      their phenophases (flowering and dispersing earlier) and showed reduced growth
      rate and increased fraction of senescent leaves. Plants growing in small
      fragments had lower survival, lower number of viable seeds, and a reduced seed
      set compared to those from large fragments. We found significant synergistic
      interactions among drivers. For example, the interaction between fragmentation
      and habitat quality led to lower survival and lower relative growth in plants
      from small and poor-quality habitat sites. Our results highlight the importance
      of studies addressing simultaneously all relevant drivers of global change
      potentially affecting plant performance under natural conditions. In addition,
      the complex responses of phenology and reproductive traits of C. hyssopifolia
      emphasize the need for studies integrating traits from vegetative to reproductive
      and from the organ to the whole-plant level.

PMID- 19769139
TI  - Comparison of multidimensional fuzzy set ordination with CCA and DB-RDA.
AB  - Multidimensional fuzzy set ordination (MFSO) is an ordination algorithm based on
      the principles of fuzzy set theory that employs a dissimilarity matrix and
      environmental or experimental variables directly in the calculation of ordination
      coordinates. The objective is similar to constrained ordinations such as
      canonical correspondence analysis (CCA) and distance-based redundancy analysis
      (DB-RDA), although MFSO employs a different conceptual and algorithmic basis.
      Results from MFSO, CCA, and DB-RDA are compared on four data sets to determine
      the relative ability of the methods to identify and quantify environmental
      variable effect sizes on community variability. Models were fit by best all
      subsets solutions and tested for significance by permutation tests. Methods were
      compared on the basis of variables selected and dimensionality of results and
      were evaluated on the basis of the correlation of the pair-wise distances of the
      derived ordination solutions to a Bray-Curtis dissimilarity matrix of the taxon
      data, and by cross-comparisons of the inertia explained by the fitted or derived
      values substituted into DB-RDA and CCA analyses. MFSO and DB-RDA achieved the
      highest correlation with the Bray-Curtis dissimilarity matrix on one data set
      each, and they tied for highest correlation on the two other data sets
      (differences <1%). CCA tied for best on one data set, tied for second on another,
      and achieved the lowest correlation on two data sets. When substituting MFSO- and
      DB-RDA-derived values into CCA, MFSO results achieved higher inertia explained on
      two of the four data sets; MFSO and DB-RDA achieved equivalent results on the
      other two. Substituting MFSO- or CCA-derived or fitted values into DB-RDA, MFSO
      results achieved higher inertia explained on all four data sets. While goodness
      of-fit statistics were often similar across methods, the methods sometimes chose
      solutions of different dimensionality or employed different variables. In
      general, all algorithms performed well, finding relatively low-dimensional
      solutions that achieved high correlation with the Bray-Curtis dissimilarity
      matrix and explained significant amounts of inertia in the eigenanalyses.
      Considering both the correlation and substitution tests, MFSO achieved the best
      results of the three methods. DB-RDA results were nearly as good as MFSO,
      however, and clearly superior to CCA.

PMID- 19769140
TI  - A hump-shaped relationship between isolation and abundance of Notonecta irrorata
      colonists in aquatic mesocosms.
AB  - We examined the relationship between the isolation of experimental aquatic
      mesocosms and the abundance of an aquatic insect colonist, Notonecta irrorata,
      over two years. We used a curve-fitting approach to assess whether linear or
      quadratic models better describe the relationship between isolation and
      abundance. For two measures of mesocosm isolation, distance to nearest source and
      distance to the largest source population, there was a significant quadratic
      relationship between isolation and abundance. Abundance of colonizing N. irrorata
      was not found to be significantly related to a third measure of isolation,
      mesocosm connectivity. These results indicate that the relationship between
      habitat isolation and colonist abundance may not be a monotonic decline across
      all spatial scales, a finding that contradicts the usual assumption incorporated
      in measures of habitat connectivity. Our results suggest that under some
      circumstances individuals that have undertaken dispersal may bypass patches they
      encounter early in this process and preferentially settle in patches encountered
      later. This behavioral preference in conjunction with decreased numbers of
      potential colonists at sites far from the source environment could lead to the
      "hump-shaped" colonist abundance by habitat isolation relationship we observed in
      this study. We suggest that simple assumptions about the relationship between
      habitat isolation and the probability a site is colonized need to be reexamined
      and alternative possible forms of this relationship tested.

PMID- 19769141
TI  - Interaction of position, litter type, and water pulses on decomposition of
      grasses from the semiarid Patagonian steppe.
AB  - Litter lignin and nutrient content, annual rainfall, and biotic activity are not
      good predictors of litter decomposition in arid and semiarid ecosystems,
      suggesting that other factors may be important in controlling carbon turnover. We
      explored the relative importance of litter position (above- vs. belowground),
      litter type (leaf vs. root), and pulsed water events (large vs. small) on mass
      loss with grass species of the semiarid Patagonian steppe. In a factorial
      experiment of mesocosms, we incubated leaf and root litter simultaneously above-
      and belowground and manipulated water availability with large and small pulses.
      Significant interactions between position and litter type and position and pulse
      sizes demonstrated interactive controls on organic mass loss. Aboveground
      decomposition showed no response to pulse size or litter type, as roots and
      leaves decomposed equally rapidly under all circumstances. In contrast,
      belowground decomposition was significantly altered by litter type and water
      pulses, with roots decomposing significantly slower and small water pulses
      reducing belowground decomposition. The results of this mesocosm experiment
      support the idea that controls other than water availability may dominate
      aboveground mass loss, while a combination of recalcitrant litter and water
      penetration in the soil profile are critical factors determining belowground
      decomposition, which is ultimately mediated by biotic degradation.

PMID- 19769142
TI  - [Introduce grades in medical education].

PMID- 19769143
TI  - [Postmenopausal hormone therapy--an update. Benefit versus risk--important to
      identify women with increased breast cancer risk].

PMID- 19769144
TI  - [Cryoballoon technique in atrial fibrillation--quick, simple and effective
      therapy].

PMID- 19769145
TI  - [Weight reduction via Internet--a small effort reaching many].

PMID- 19769146
TI  - [Quantitative lower respiratory tract cultures and how to interpret them.
      Infection must be discriminated from colonization].

PMID- 19769147
TI  - [Pulmonary arterial hypertension. New therapeutic principles improve treatment of
      a rare condition].

PMID- 19769148
TI  - [To have or to experience--that is the question. The difference between believing
      one is ill and being ill].

PMID- 19769149
TI  - [Misleading dissertation on mobile phone radiation].

PMID- 19769150
TI  - [Quality measurement is necessary--but can not determine health care quality].

PMID- 19769151
TI  - [Life style changes and drugs complete each other].

PMID- 19769152
TI  - [Time to change continuing medical education!].

PMID- 19769153
TI  - [Ethics, priorities and value basis].

PMID- 19769154
TI  - [The difficulty of correct quoting--good evidence of Murphy's law].

PMID- 19769155
TI  - [Production of human papillomavirus type 16 virus-like particles and its
      immunogenicity].
AB  - HPV16 L1 gene was amplified from HPV16 positive vaginal secretion sample by PCR,
      and inserted into pTO-T7 to obtain the recombinant expression vector pTO-T7-HPV16
      L1. Then, the pTO-T7-HPV16-L1 was transformed into E. coil strain ER2566 and the
      recombinant protein HPV16 L1 was expressed in soluble form. After purification by
      ammonium sulfate precipitation, ion-exchange chromatography, and hydrophobic
      interaction chromatography, the recombinant protein HPV16 L1 had a purity of more
      than 98%. By removing DTT, purified HPV16 L1 proteins self-assembled in vitro
      into VLPs with the diameter of 50 nm. The vaccination experiments on experimental
      animals showed the VLPs could elicit high titer of neutralizing antibodies
      against HPV 16. HPV16 VLPs with high immunogenicity and high purity can be
      produced easily and effectively from an E. coli expression system in the study,
      and thus can be used in structure investigation and HPV16 vaccine development.

PMID- 19769156
TI  - [Outbreak of acute hemorrhagic conjunctivitis in Beijing City in 2007 caused by
      coxsackievirus A24 variant: molecular identification and phylogenetic analysis].
AB  - In 2007, an outbreak of acute hemorrhagic conjunctivitis (AHC) occurred in
      Beijing. In order to identify the etiology of this outbreak, 57 eye conjunctival
      swabs were collected from 57 outpatient patients, and detected for adenovirus,
      human enterovirus 70 (HEV70) and Coxsackievirus A24 variant (CVA24v) genes by
      using RT-PCR or PCR methods. The results showed that 38 were positive for CVA24v,
      the positive rate was 66.7%, but none was positive for HEV70 and adenovirus,
      showing that this outbreak was caused by CVA24v. 9 viral isolates were obtained
      from 57 clinical specimens by using viral isolation method, and all were
      identified as CVA24v by molecular typing method. All 9 CVA24v isolates were
      performed by VP1 sequencing, the results showed that except for strain
      0744/BJ/CHN/2007, the variability at nucleotide acid level and amino acid level
      among other 8 CVA24v were relatively low, and the homologies were more than 99.6%
      and 100.0%, respectively; the homologies of nucleotide acid and amino acid
      between strain 0744/BJ/CHN/2007 and other 8 CVA24v were 96.8%-97.2% and 99.7%,
      respectively. Phylogenetic analysis of 9 CVA24v revealed that they represented
      the Clade 4 and Clade 5 in Group I, showed that this outbreak was caused by at
      least 2 viral transmission chains. Comparing to 3C region of CVA24v frequently
      used before, VP1 region was considered as the most rigorous target for molecular
      epidemiology study of CVA24v. To enhance the research of sero-epidemiology and
      molecular epidemiology of CVA24v and to know the genetic characterizations and
      molecular evolution of CVA24v are most important to prevent and control the
      outbreaks of AHC in China.

PMID- 19769157
TI  - [The impact of the HIV-1 envelope (Env) mutation on its assembly of functional
      pseudovirus].
AB  - To find out whether the mutations of HIV-1 Env have influence on the assembly of
      pseudovirus and their abilities to infect cells, site-directed mutation
      (A457D)was performed using cycling mutagenesis and selection of mutants with
      DpnI. Transformation and plasmid purification technologies were used to obtain
      mutated env clone. Then both the prototype and the mutant were co-transfected
      with pSG3(delta(env)) to 293FT cells, respectively. Single-cycle infection assay
      was employed to analyze the effect of the prototype and the mutant on the ability
      of functional pseudovirus assembly. The transient expression of both the
      prototype S12-42-1 and mutant S12-42M were confirmed by Western blot essay. The
      S/CO value was less than 1 for S12-42-1 and 6.65 for S12-42M, demonstrating the
      functional pseudovirus was generated only for S12-42M. So mutation on HIV-1 Env
      has influence on the assembly of pseudovirus and their abilities to infect cells.

PMID- 19769159
TI  - [The preparation of monoclonal antibodies against AAV2 and study on their
      characterizations].
AB  - 7 strains of stable cell lines secreting monoclonal antibodies against AAV2
      capsids were obtained by immunizing BALB/C mice with highly purified recombinant
      adeno-associated virus. Among them, the monoclonal antibodies B10 and G4 had
      neutralizing activity, and their subtypes were IgG1 and IgG2a, respectively. The
      binding characterizations of the two neutralizing antibodies were studied. Both
      B10 and G4 showed serotype specific binding activities to rAAV2 virus particles
      other than AAV1, AAV5, and AAV8, and the binding could not be blocked by heparin.
      After incubating with the two antibodies separately, rAAV2 viruses could still
      bind to sensitive cell line BHK-21, suggesting that the binding sites of the two
      antibodies to rAAV2 located at different positions on viral particle surface from
      the primary receptor binding sites of AAV2. Western blotting assay showed that
      B10 could bind to VP1, VP2 and VP3 of rAAV2. However, G4 bound none of them. The
      results suggested that B10 recognized a linear epitope of AAV2 capsid, whereas G4
      probably recognized a conformational epitope on the surface of AAV2 virus
      particle. The two antibodies with different characteristics provided valuable
      tools for AAV2 virus particles detection and infection processes.

PMID- 19769158
TI  - [Two HCV vaccines based on adeno-associated virus vectors elicited durable and
      effective immune responses in mice].
AB  - Recombinant adeno-associated viruses (rAAV) vectors have been shown to mediate
      long-term transgene expression in mice and nonhuman primates. We have adapted
      viral vector system based on two rAAV vectors, namely rAAV1 and rAAV2. We have
      generated rAAV vectors expressing the envelope glycoprotein (E1 and E2) derived
      from Chinese HCV patient (genotype 1b) and used these to immunize BALB/c mice. We
      detected the total antibody titer by IFA and neutralizing antibody (nAb) using in
      vitro HCV neutralizing assays based on HCV pseudotyped particles. Furthermore,
      IFN-gamma ELISpot assay was used to assess the T cellular response against HCV at
      12 weeks after rAAV1-E1E2 immunization. We also analyzed HCV envelope
      glycoprotein expression in muscle of rAAV1-E1E2 immunized mice. Our data showed:
      (i) rAAV1 directed long-term expression of HCV genes in mice; (ii) immunized
      intramuscularly with a single dose of rAAV elicited durable and effective immune
      responses in mice; and (iii) Moreover, rAAV1-E1E2 induced higher total antibody
      and nAb titers than rAAV2-E1E2 did. These data suggest that rAAV1 vectors could
      stimulate robust, durable, and effective immune responses against HCV.

PMID- 19769160
TI  - [The cloning, expression and structural analysis of putative unknown protein Orf
      9b in SARS-CoV].
AB  - Orf 9b was amplified by PCR from SARS-CoV genome and cloned into the Nco I and
      Bam HI sites of the pET32c expression vector, and then recombinant plasmid pET32c
      Orf 9b was constructed. The recombinant fusion protein Orf 9b was expressed by
      IPTG induction and purifed. After being cleaved by rEK, Orf 9b protein with MW 11
      kD was separated and collected. It was demonstrated by ELISA that the purified
      Orf 9b protein could react with sera of SARS rehabilitaion patients but not with
      sera from healthy donors. CD and Infrared spectroscopy were used to predict the
      secondary structure of the purified Orf 9b protein. The distribution percentages
      for the the secondary structures of alpha-helix, beta-sheet, and random coil in
      the Orf 9b protein estimated by CD were 12.5%, 40%, and 47.5%, respectively,
      while the same parameters estimated by Infrared spectroscopy were 13.7%, 47.5%,
      and 37.9%, respectively. The results obtained by the two methods were
      substantially identical and showed that the structure of the Orf 9b protein
      consisted mostly of beta-sheet, and comprised only few alpha-helix. The
      acquisition of purified protein and the structural information presented herein
      may provide foundation for further functional study.

PMID- 19769161
TI  - [Construction of mammalian cell lines continuously expressing JEV structural
      proteins].
AB  - Based on the infectious clone of JEV vaccine strain SA14-14-2, prM-E genes and C
      prM-E genes were cloned into pCDNA3.1 vector. The recombinant plasmid pCJE-ME was
      transfected into BHK-21 cells, the expressed proteins were toxic to the cell
      growth and accelerated the cell death. But when transfected with the plasmid pCJE
      CME, the cell lines continuously expressing structural proteins could be selected
      with G418. And the expression products of pCJE-CME vector could be detected by
      ELISA, Western Blot and IFA assay. It showed that the JEV capsid protein could
      enhance the stability of the cell lines expressing the structural proteins. The
      established cell lines can make the acquirement of the virus-like particles much
      easier.

PMID- 19769162
TI  - [Using real-time PCR to evaluate the effect of viral inactivation by Methylene
      Blue with visible light].
AB  - To investigate the feasibility of using Real-Time PCR to evaluate the
      effectiveness of Sindbis virus inactivation by Methylene Blue with visible light.
      Sindbis virus was treated by Methylene Blue with different intensity of visible
      light and the transcribed cDNA was quantified by Real-Time PCR. Residual
      infectivity of treated virus was tested by cell infection method as parallel
      control at the same time. The residual infectivity of virus decreased from 6.50
      lgTCID50/mL to under the limit of detection as light intensity increased.
      Meanwhile, the quantity of virus cDNA decreased significantly (P < 0.05), which
      correlated to the decline of virus infectivity (R2 > 0.98). Methylene Blue with
      visible light could cause lesion to nucleic acid of Sindbis virus, the extent of
      which was light intensity-dependent and correlated to the decrease of virus
      infectivity. The results demonstrated that Real-Time PCR can be a useful tool for
      evaluating effect of virus inactivation after Methylene Blue treatment with
      light.

PMID- 19769163
TI  - [Rapid detection of norwalk GII with reverse transcription loop-mediated
      isothermal amplification].
AB  - To develop a reverse transcription-loop-mediated isothermal amplification (RT
      LAMP) assay for rapid and sensitive detection of Norwalk GII. 4 primers which
      recognized 6 distinct regions on the RNA-dependent RNA polymerase gene of Norwalk
      GII were designed and used for LAMP assay. Norwalk GII RNA was amplified under
      isothermal conditions (65 degrees C) for 120 min, and LAMP results were then
      judged with naked eye, SYBR Green I staining, electrophoretic analysis and
      restriction digestion. To evaluate the specificity of the RT-LAMP, 48 fecal
      specimens of Norwalk GII and 12 fecal specimens of group A rotaviruses were
      tested. To compare the sensitivity of the RT-LAMP with that of conventional RT
      PCR, Norwalk GII RNA was serially diluted and amplified by RT-LAMP and RT-PCR,
      respectively. With 46 fecal specimens of Norwalk GII, observation with naked
      eyes, SYBR Green I staining and electrophoretic analysis were able to detect the
      PCR products in the RT-LAMP assay. The specificity of RT-LAMP products was also
      confirmed by digestion of the RT-LAMP products with restriction enzymes. No RNA
      amplification was observed in 2 fecal specimens of Norwalk GII and 12 fecal
      specimens of group A rotaviruses. The specificity of the RT-LAMP assay with
      regard to RT-PCR were 100% for Norwalk GII. The detection limits of RT-LAMP was
      15.6 pg/tube for Norwalk GII and similar to that of a RT-PCR assay. Compared to
      RT-PCR, the RT-LAMP assay has been proven to be a rapid, sensitive, specific and
      accurate method for detection of the Norwalk GII in fecal specimens, and that RT
      LAMP assay is potentially useful for the rapid detection of Norwalk GII from
      fecal specimens in outbreaks of infectious diarrhea.

PMID- 19769164
TI  - [An undamaged bulge in epsilon is essential for initiating priming of DHBV
      reverse transcriptase].
AB  - Previously, we have established an epsilon library and selected out a series of
      RNA aptamers with higher affinity to P protein based on the in vitro Systematic
      Evolution of Ligands by Exponential Enrichment (SELEX) in duck hepatitis B virus
      (DHBV) system. In order to study the structural elements within the epsilon that
      is essential for initiating priming of HBV reverse transcriptase (P protein), all
      selected aptamers were subjected to in vitro priming assay and RNA secondary
      structure probing. We found that all those aptamers supporting priming had an
      undamaged bulge, while those lacking of the bulge no more support priming. Our
      results suggest an undamaged bulge within Depsilon is indispensable for
      initiating priming of P protein.

PMID- 19769165
TI  - [The changes of peripheral blood leucocytes subpopulation after challenge with
      CSFV virulent strain Shimen].
AB  - To investigate the effects of classical swine fever virus (CSFV) virulent strain
      Shimen (SM) infection on piglets peripheral blood leucocytes, the 60-days
      weanling piglets were infected with the shinen strain and the peripheral blood
      samples of the piglets were collected to analyze the kinetics of the CSEV nucleic
      acid, the peripheral blood leucocytes subpopulation and SLA molecule expression
      on the peripheral blood leukocytes. The results showed that the piglets rectal
      temperature increased 48 hours after intramuscular injection of CSFV SM strain,
      the CSFV nucleic acid was detected in the peripheral blood at 2DPI, the content
      of CSFV nucleic acid increased and up-regulated to a peak at 6DPI as 10 (4.84 +/-
      0.98 times as 2DPI. The amount of WBC, LYM and PLT significantly decreased, where
      in the amount of WBC decreased to 65.87% at 1DPI and 50% at 2DPI respectively;
      the amount of LYM decreased to 70.68%, 47.88% and 23.29% at 1DPI, 2DPI, and 3DPI,
      respectively; the amount of PLT decreased day by day and to 34.59% at 6DPI; the
      amount of NK, gammadeltaT, Tc, Th, CD3+ CD4+ CD8+ and CD3- CD4- CD8- cells
      decreased after infection; 78.49% of NK cells decreased at 1DPI and then there
      was no significant change from 2DPI to 6DPI. The amount of gammadeltaT, Tc, CD4-
      CD8- CD3-,CD4+ CD8+ CD3+ cells decreased to 41.74%, 43.83%, 15.87%, and 32.96% at
      3DPI, respectively, However, the amount of T helper cells decreased continually
      to 42.95% at 6DPI; the amount of SLA I positive lymphocytes decreased
      significantly and the amount of SLA I positive CD3 cells decreased to 23.07% and
      15.38% at 1DPI and 2DPI respectively; the SLA I positive granulocytes increased
      continually from 92.20% at 1DPI to 98.30% at 3DPI; the amount of CD3 SLA II +
      cells in lymphocytes decreased from 1.38% at 1DPI to 0.22% at 2DPI, while the SLA
      II + granulocytes increased continually to a peak at 3DPI and 53.76% of
      granulocytes expressed the SLA II molecule, but the percentage of the
      granulocytes expressing SLA II molecules decreased to 12.54% and 4.06% at 4DPI
      and 5DPI respectively. The study indicated that the CSFV SM strain infection
      could escape the immune surveillance and cause immunosuppression through
      inhibiting the host's innate antiviral immunity and the SLA molecule expression
      to affect the antigen presentation.

PMID- 19769166
TI  - [Construction and in vitro evaluation of an infectious clone of the equine
      infectious anemia virus vaccine strain EIAV(FDDV) with four reverse-mutated
      vaccine-specific sites in the S2 gene].
AB  - To elucidate the function of the S2 gene in equine infectious anemia virus (EIAV)
      and its role in the attenuation of the Chinese attenuated EIAV vaccine strains,
      the S2 in the EIAV vaccine strain EIAV (FDDV) was reverse-mutated and the in
      vitro replication character of the resultant virus was evaluated. Based on the
      sequence variation of the S2 gene between the EIAV virulent strains and vaccine
      strains, all the four vaccine-specific sites in the S2 of an EIAV(FDDV)
      infectious clone, pFDDV3-8, were reverse-mutated to the sequences of the virulent
      strain EIAV(DV115). The reverse-mutated molecular clone pFDDVS2r1-3-4-5 was used
      to transfect fetal donkey dermal (FDD) cells for rescuing the derived virus
      vpFDDVS2r1-3-4-5. The production and replication of vpFDDVS2r1-3-4-5 in FDD cells
      were proved by RT-PCR, immune fluorescence assay and reverse transcriptase
      activity assay. Typical virons of EIAV were clearly observed under the electron
      microscopy. The parallel analysis of the dynamic replication of the reverse
      mutated viral clone vpFDDVS2r1-3-4-5 and its parental virus vpFDDV3-8 showed that
      the virus with four reverse mutations in the S2 replicated only slightly slower
      than its parental vaccine strain in FDD cells. This result implicates that the
      mutations in the S2 of the EIAV vaccine strains did not significantly alter the
      viral replication in vitro. Further studies on the in vivo replication of the
      reverse-mutated viral clone are required for understanding the relationship
      between the S2 and the attenuated pathogenesis of EIAV attenuated vaccines.

PMID- 19769167
TI  - [Studies on the apoptosis of RK13 cells induced by rabbit hemorrhagic disease
      virus].
AB  - The apoptosis of RK13 cells induced by RHDV was investigated with DAPI staining,
      DNA ladder, Caspase 3 activity and flow cytometry, etc. The results showed that
      nuclear staining of infected cells with DAPI showed gradually morphological
      changes of the nuclei. As shown in the paper, a canonic oligonucleosome-sized DNA
      ladder was observed in cells harvested at 24h, 48h and 72h post-infection,
      confirming that DNA fragmentation was induced by RHDV infection. The results of
      flow cytometry showed that about 63% of cells were in apoptosis at 48h post
      infection. Besides, we also demonstrated that the activation of Caspase 3
      occurred during the infection process. In conclusion, our results showed that
      apoptosis in RHD might be determinant in the development of the pathogenesis of
      RHD.

PMID- 19769168
TI  - [Protective mucosal immunity and HIV-1 mucosal vaccine strategy].

PMID- 19769170
TI  - The one-stop health stock.

PMID- 19769169
TI  - [Bimolecular fluorescence complementation and its application in plant virology].

PMID- 19769171
TI  - Portfolios grow fatter ... ... but not enough to make up for 2008 losses.

PMID- 19769172
TI  - They know it when they see it. Feds say Iowa doc pay violated Stark rules, but
      don't explain rationale.

PMID- 19769173
TI  - Above and beyond. Regional GPOs work to offer value, services that their national
      counterparts often don't provide.

PMID- 19769174
TI  - A moment of silence. Hopefully Kennedy's death will help expel vitriol from
      healthcare debate.

PMID- 19769175
TI  - No mere cookbook. Evidence-based medicine safe harbor would cut unneeded tests,
      boost quality.

PMID- 19769176
TI  - [Management of herpes zoster infection].
AB  - Approximately 10 to 30% of the population will suffer from herpes zoster (HZ)
      during their lifetime. Prompt treatment of acute HZ with acyclovir, valacyclovir
      or famciclovir is recommend, if patients are over 50 years old or have severe or
      moderate pain or severe or moderate rash or they are immonocompromised or suffer
      from herpes zoster ophtalmicus. Zoster lesions contain high concentrations of
      Varicella zoster virus that can spread, and cause chicken pox. There is no
      universal recommendations for varicella vaccination. It has been shown that
      zoster vaccine markedly reduced morbidity from herpes zoster and postherpetic
      neuralgia among older adults.

PMID- 19769177
TI  - [Acute polyradiculitis--from prickling to intensive care].
AB  - Characteristic symptoms of acute polyradiculitis are parestesia beginning from
      the feet and a symmetrically ascending myasthenia. The symptomatology, which may
      vary from mild asthenia to complete tetraplegia, may be accompanied by asphyxia
      and symptoms of the autonomic nervous system and cranial nerves. Polyradiculitis
      is often preceded by an infection. An elevated protein level of the cerebrospinal
      fluid without cellular reaction is the typical finding, but a specific laboratory
      test is not available. The clinical course is monophasic and relapses are
      uncommon. The natural prognosis for recovery is fairly good, but one fifth are
      left with functional impairment and the disease may even be fatal.

PMID- 19769178
TI  - [Cardiorenal syndrome].
AB  - Cardiorenal syndrome refers to the interaction between the heart and the kidneys,
      in which the disease state of one organ alters and impairs functioning of the
      other. A more precise definition has not been presented before, but a new
      classification has now been published. Examples of clinical manifestations of the
      syndrome include profuse and serious cardiac events in dialysis patients, often
      simultaneously occurring renal insufficiency in a cardiac patient as well as
      rapid impairment of renal function and diuretic resistance in connection with
      acute cardiac insufficiency.

PMID- 19769179
TI  - [Clozapine in the treatment of under-age schizophrenia].
AB  - In as many as one third of those afflicted with schizophrenia, the symptoms have
      emerged before adulthood. Early-onset schizophrenia is often a long-term illness
      with an unfavorable prognosis. Clozapine is more effective than other
      antipsychotic drugs in adults, but its use is limited by potential adverse
      effects, of which agranulocytosis is the most serious one. According to the
      treatment practice for adults, clozapine emerges inevitably as a drug option for
      difficult-to-manage schizophrenia in an under-aged person. The few studies
      conducted on the subject speak for the use of clozapine also in the under-aged.

PMID- 19769180
TI  - [Acanthamoebal keratitis].
AB  - Acanthamoebae are protists causing opportunistic infections to immunocompromised
      patients, and refractory keratitis also to others. Factors predisposing to
      Acanthamoebae keratitis include conditions that impair corneal defence
      mechanisms, such as traumas or use of contact lenses combined with exposure to
      contaminated water, for example. Delays in diagnosis and therapy will worsen the
      prognosis of acanthamoebal keratitis. In recent years, noninvasive in vivo
      confocal microscopy that enables an early diagnosis and is quicker than before,
      has become more common alongside conventional diagnostic methods, i.e. culture
      and smears made from corneal specimens.

PMID- 19769181
TI  - [Planning of a questionnaire survey].
AB  - A questionnaire will prove most useful, when it has been tested, is reliable,
      felicitous, reproducible, technically sound, clear and when needed, identifiable.
      Sending, reception and storage of the form must also be planned beforehand in
      order to guarantee a good start for analyzing the results. Significant factors
      related to the answering to questionnaire surveys include written feedback
      received by the participants after the study, fees, brevity, readability,
      personality of the forms and statements in the covering letter of benefits gained
      by the study management and the society subsequent to answering.

PMID- 19769182
TI  - [Drug therapy for glaucoma].
AB  - Drug therapy for glaucoma is based on lowering of intraocular pressure regardless
      of the pressure level, at which the disease has been diagnosed. Earlier it was
      empirically clear that in disease cases involving a high pressure, drug therapy
      will slow down the advancement of the disease. During the last ten years
      scientific evidence has accumulated indicating that a disease with normal
      pressure is also worth treating. Drug therapy can also postpone the onset of
      glaucoma at a time when intraocular pressure is high, yet without structural or
      functional damage.

PMID- 19769183
TI  - Remote access. A heartland doctor takes a do-it-yourself approach to office IT.

PMID- 19769184
TI  - Free up your fees. Health plan payment schedules aren't set in stone, negotiate
      for what you're worth.

PMID- 19769185
TI  - Code green. Communicating with your coders is a great way to boost income.

PMID- 19769186
TI  - Cross coverage needs guidelines, understanding.

PMID- 19769187
TI  - Revamping your practice's retirement plan.

PMID- 19769188
TI  - A great idea turning bad. EHR mandates would feel better if they came with tort
      reform.

PMID- 19769189
TI  - Proteomic analyses of recombinant human follicle-stimulating hormone and urinary
      derived gonadotropin preparations.
AB  - OBJECTIVE: To understand the properties of each available gonadotropin
      preparation, especially in terms of the differences between urinary-derived and
      recombinant preparations. STUDY DESIGN: Human menopausal gonadotropin (hMG),
      highly purified urinary-derived follicle-stimulating hormone (uFSH-HP) and
      recombinant FSH (rFSH) were subjected to 2-dimensional gel electrophoresis (2
      DE), and protein spots were visualized by silver-staining procedures. Major spots
      were analyzed by mass spectrometry. Fluorescent-labeled preparations were also
      subjected to 2-DE to evaluate the quantities of FSH isohormones contained in each
      preparation. RESULTS: 2-DE and mass spectrometry analyses of hMG identified many
      extracellular proteins as major impurities and several plasma membrane proteins
      including prion proteins. Both uFSH-HP and rFSH demonstrated slight impurities
      and showed several alpha and beta subunit isohormones. rFSH contained higher
      amounts of the basic isohormones of the alpha subunit than uFSH-HP, whereas the
      predominance of the basic isohormones was less significant in the beta subunit.
      CONCLUSION: Proteomic analyses demonstrated the detailed protein profiles of each
      preparation. Differences in the quantities of alpha subunit isohormones may
      contribute to the variations in FSH activity observed between recombinant and
      urinary-derived FSH preparations.

PMID- 19769190
TI  - Unfulfilled postpartum sterilization requests.
AB  - OBJECTIVE: To determine individual and delivery characteristics of women least
      likely to obtain a requested postpartum tubal ligation (PPTL) and, secondarily,
      to compare the postpartum contraceptive choices of women with an unfulfilled
      sterilization request to women not requesting a PPTL. STUDY DESIGN: Record review
      ofwomen delivering a liveborn singleton between December 2007 and May 2008 at the
      University of Texas San Antonio. Primary outcomes were risk factors for not
      receiving a requested PPTL. Secondary outcome was to compare the postpartum
      contraceptive choices of women not receiving a PPTL to controls, women not
      requesting a PPTL. RESULTS: During the observation period, 429 of 1,460 women
      requested a PPTL; 296 (69%) received the procedure, and 133 (31%) did not. The
      majority of patients (332/429, 77.4%) were Hispanic. Pretest power analysis
      concluded that 107 women were required in each group. Cesarean delivery was
      associated with the highest likelihood of receiving a PPTL. Women receiving a
      PPTL were more likely (p < or = 0.05) to be a documented U.S. resident, married,
      of lower parity, have private or any medical insurance and to have received any
      prenatal care. Postpartum contraception among women with unfulfilled
      sterilization requests was similar to that among controls. CONCLUSION: Although
      financial and policy barriers exist, the majority of patients requesting a PPTL
      received the procedure.

PMID- 19769191
TI  - Over-the-counter ovulation prediction devices: do accompanying instructions
      adhere to low-literacy guidelines?
AB  - OBJECTIVE: To evaluate readability and layout features of English-language
      instructions accompanying brandname urinary- and salivary-based over-the-counter
      (OTC) ovulation prediction devices (OPDs). STUDY DESIGN: We identified and
      purchased 6 urinary-based and 4 salivary-based OTC OPDs. McLaughlin's Simplified
      Measure of Gobbledygoop was used to calculate reading grade level, and prominent
      text point size was measured throughout the instructions. Total number and
      dimensions of illustrations were tallied. We also assessed layout features
      derived from the User-Friendliness Tool (UFT), including layout features, graphic
      characteristics, presence of a clear message and presentation of manageable
      information. RESULTS: Overall reading level of OTC OPD instructions ranged from
      8th to 12th grade (mean +/- SD = 10.2 +/- 1.3). Mean page length was 29.0 +/-
      12.8 cm, while average page width was 30.7 +/- 14.7 cm. Average text point size
      was 8.2 +/- 1.5 (range, 6-10). Illustrations were used throughout instructional
      materials (range, 5-10). None of the instructions scored high in all criteria on
      the UFT. CONCLUSION: Most OTC OPD instructions are written above the recommended
      sixth grade level and lower, printed in a font size smaller than suggested and
      illustrated inadequately to foster successful patient education.

PMID- 19769192
TI  - Correlation of increased fetal asymmetry with shoulder dystocia in the
      nondiabetic woman with suspected macrosomia.
AB  - OBJECTIVE: To determine if the sonographic difference of > or = 2.6 cm between
      the fetal abdominal diameter (AD) and biparietal diameter (BPD), a proxy for
      fetal asymmetry, has an association with shoulder dystocia in nondiabetic women
      with suspected macrosomia. STUDY DESIGN: A retrospective cohort study was
      performed in 3 Southern California tertiary care hospitals. We identified
      patients in whom sonographic evaluation after 36 weeks' gestation demonstrated an
      estimated fetal weight > 4,000 g. Additional prenatal and delivery information
      was obtained from hospital records. RESULTS: We identified 159 subjects who met
      ultrasound criteria and underwent a vaginal delivery. The mean AD-BPD difference
      in the shoulder dystocia group was significantly greater than in the group
      without shoulder dystocia (2.76 +/- 0.59 vs. 2.37 +/- 0.56, p = 0.001). The
      adjusted OR of shoulder dystocia in the group with an AD-BPD difference > or =
      2.6 was 3.67 (95% CI, 1.44-9.36). CONCLUSION: Significant discordance between the
      fetal head and abdomen appears to be associated with an increased rate of
      shoulder dystocia in a nondiabetic population with suspected macrosomia.

PMID- 19769193
TI  - Association between serum estradiol level and intraocular pressure in
      postmenopausal women.
AB  - OBJECTIVE: To evaluate the association between serum estradiol (E2) level and
      intraocular pressure (IOP) in Korean postmenopausal women STUDY DESIGN: From
      January 2000 to December 2006, serum concentration of E2 and IOP were measured in
      8,674 postmenopausal women. Serum concentration of E2 was measured by
      radioimmunoassay. The IOP was measured using Goldmann's applanation tonometer.
      All data were analyzed with correlation analysis, Student's t test and analysis
      of variance. RESULTS: The mean age of the study subjects was 59.57 +/- 8.54
      years. The mean E2 concentration was 22.17 +/- 6.08 pg/mL and the mean IOP was
      12.23 +/- 2.20 mm Hg for the average of both eyes. In correlation analysis, no
      significant association was found between IOP and age or IOP and serum E2
      concentration. When we divided a total of 8,674 women into 4 groups according to
      the E2 concentration (< or = 10, 10-20, 20-30 and >30 pg/mL, respectively), the
      IOPs of the 4 groups did not differ significantly. CONCLUSION: This study
      suggests that the IOP in Korean postmenopausal women might not be directly
      associated with serum E2 concentration.

PMID- 19769194
TI  - Predictors of advanced pelvic organ prolapse in Asian women.
AB  - OBJECTIVE: To investigate risk factors for advanced pelvic organ prolapse (POP)
      in Asian women. STUDY DESIGN: This was a case-control study of Asian women
      referred for POP or incontinence over a 10-year period at San Francisco General
      Hospital. Details of a structured pelvic examination and demographic information
      were abstracted from medical records. Cases were women with advanced (beyond the
      hymenal remnant) POP, while patients with a lesser degree of prolapse served as
      controls. Categorical variables were analyzed using chi2 or Fisher's exact test
      (where appropriate), while continuous variables were analyzed with Student's t
      test. Logistic regression was used for multivariate analysis. RESULTS: One
      hundred thirty Asian women were identified. Sixty-six women had advanced prolapse
      of some portion of their vagina. Increasing parity was associated with advanced
      prolapse of the anterior compartment of the vagina (adjusted OR 1.56, 95% CI 1.22
      2.00). Previous hysterectomy appears to be protective of advanced prolapse of the
      anterior vagina (adjusted OR 0.09, 95% CI 0.01-0.81). CONCLUSION: Similar to the
      Caucasian population, Asian women with higher parity are at increased risk for
      prolapse of the anterior compartment of the vagina. However, previous
      hysterectomy appears to be protective of future prolapse in Asian women.

PMID- 19769195
TI  - Symptoms of anal incontinence and impact on sexual function.
AB  - OBJECTIVE: To evaluate whether symptoms of anal incontinence (AI) have an impact
      on sexual function in a cohort of women with pelvic floor disorders and/or
      incontinence. STUDY DESIGN: We analyzed a cohort of women presenting to an
      academic urogynecology practice. The control group consisted of those who
      answered "no" to questions 9-11 on the Pelvic Floor Distress Inventory. The AI
      group consisted of those selecting "yes" to at least 1 of these questions.
      Student t test was used to compare differences between groups for the Pelvic
      Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12). RESULTS: The
      control group had a significantly lower mean score on the PISQ-12 than the AI
      group. There was no difference in PISQ-12 scores when controlling for stage of
      prolapse. CONCLUSION: Symptoms of AI were not associated with worse
      sexualfunction as measured by the PISQ-12.

PMID- 19769196
TI  - Management of relapsing cervical intraepithelial neoplasia.
AB  - OBJECTIVE: To evaluate relapsing cervical intraepithelial neoplasia (CIN) and
      establish the criteria of recurrence to assess management by laser CO2. STUDY
      DESIGN: Patients with histologically proved CIN after a primary conservative
      approach were the study population. Disease relapse was considered as residual or
      recurrent if diagnosed within or after the first year of follow-up. RESULTS:
      There were 333 patients assessed in our study. Residual disease was found in 80
      patients (24%) and recurrent disease in 253 patients (76%). Histologic findings
      were compatible with CIN 2-3 in 127 and with CIN 1 in 206 patients. Laser CO2
      conization was offered to 240 patients, laser ablation to 10 patients and
      combination treatment to 31 patients, whereas 52 patients were assigned to follow
      up. Involved resection margins were present in 37 patients, but only when the
      endocervical margin was involved was there a significant association with
      recurrence rate. CONCLUSION: Relapsing CIN creates difficulties in management; we
      recommend that patients should be treated in tertiary centers with high
      expertise. Laser CO2 seems to be a safe and efficacious method for treating
      relapsing CIN.

PMID- 19769197
TI  - Secondary cytoreduction in epithelial ovarian cancer recurrence: a perspective
      from a regional cancer center in India.
AB  - OBJECTIVE: To assess the impact of secondary cytoreduction on survival in our
      patients with recurrent epithelial ovarian cancer. STUDY DESIGN: Between January
      2001 and December 2006 all patients who underwent surgical resection of
      documented epithelial ovarian cancer recurrence were identified from the hospital
      tumor registry database. Criteria for inclusion were disease-free interval >6
      months after completion of primary treatment with clinical and/or radiographic
      findings suggestive of recurrence. Patients with borderline histology and those
      operated for malignant bowel obstruction were excluded. All patients were
      followed until August 2008 or death. Survival analysis was done using the Kaplan
      Meir method. RESULTS: Forty-eight patients, aged 28-68 years (mean, 50) satisfied
      the inclusion criteria. The majority had advanced disease at initial diagnosis.
      The most common histology was serous. Optimal cytoreduction was attained in 29
      patients (60.4%). Estimated 5-year overall survival was 32.25% CONCLUSION: The
      present data show that a macroscopically complete salvage surgical cytoreduction
      is possible for most patients with recurrent epithelial ovarian cancer and
      confers a definite survival benefit to the patient.

PMID- 19769198
TI  - Mifepristone followed by high-dose oxytocin drip for second-trimester abortion: a
      randomized, double-blind, placebo-controlled, pilot study.
AB  - OBJECTIVE: To study the effect of mifepristone for priming and induction of
      second-trimester abortion in conjunction with a high-concentration oxytocin drip.
      STUDY DESIGN: Prospective, randomized, placebo-controlled, pilot study. Thirty
      patients with 14-25 weeks' gestational age abortion received either 600 mg of
      mifepristone or placebo in 3 identical capsules followed, 48 hours later, by a
      high-concentration oxytocin drip (HCOD). RESULTS: The mifepristone group showed
      significantly higher success rates as compared to the placebo group (92.3% vs.
      52.9%, p<0.05). The time interval to abortion (from beginning of HCOD) was also
      significantly shorter in the mifepristone group as compared to the placebo group
      (11.3 +/- 6.0 hours vs. 17.6 +/- 6.5 hours, p <0.05). Probability of success as
      calculated by the Kaplan-Meier method was found to be highly significant (log
      rank test p = 0.001). CONCLUSION: Our results suggest that mifepristone is very
      effective for priming and induction of second-trimester abortion and shortens
      significantly the time interval to evacuation following HCOD.

PMID- 19769199
TI  - A rare malignant Brenner tumor of the ovary in a 77-year-old woman: a case
      report.
AB  - BACKGROUND: A malignant Brenner tumor is a rare form of invasive epithelial
      ovarian cancer and is extremely uncommon in women > 65 years of age. We present a
      case of an invasive Brenner tumor of the ovary in a woman greater than age 70.
      CASE: A 77-year-old woman presented with a rare, invasive Brenner tumor of the
      ovary. She was referred for evaluation of a complex pelvic mass and elevated
      serum CA-125. Treatment included complete surgical resection and staging
      procedure. Pathology revealed a malignant Brenner tumor. Immunohistochemical
      staining with cytokeratin 7 was positive, with cytokeratin 20 was negative, and
      was positive for uroplakin III and thrombomodulin. CONCLUSION: The histologic
      appearance of malignant Brenner tumor is similar to that of transitional cell
      cancer of the ovary and transitional epithelium of the urinary bladder.
      Immunohistochemical staining of malignant Brenner tumor often demonstrates
      positivity for uroplakin III, thrombomodulin and cytokeratin 7 and negativity to
      cytokeratin 20. The mainstay of treatment is surgical resection, but the exact
      regimen and benefit of adjuvant therapy remain unknown.

PMID- 19769200
TI  - Successful treatment of orgasmic dysfunction using specialized physical therapy:
      a case report.
AB  - BACKGROUND: Sexual dysfunction in women is a challenging and difficult problem to
      treat. There can be multiple etiologies for these problems, and they can present
      differently in patients. Practitioners and patients can become frustrated when
      treatment becomes elusive. CASE: A patient complained of unilateral pelvic pain
      only with orgasm. Treatment involved specialized physical therapy. CONCLUSION:
      Pelvic pain related to intercourse is a common complaint in gynecologic practice.
      Specialized physical therapy may play a role in resolving sexual dysfunction in
      certain patients.

PMID- 19769201
TI  - A unique hypnotherapeutic approach to interstitial cystitis: a case report.
AB  - BACKGROUND: Interstitial cystitis (IC) is a disease of the urinary bladder in
      which the lining may become inflamed and ulcerated, resulting in pain, urinary
      frequency and urgency. While traditional hypnotherapy has been shown effective in
      treating IC, some clients do not want the use of suggestion, daily self-hypnosis
      or extended treatment. CASE: A woman presented with a 9-year medical history of
      IC without resolution despite multiple medical treatments. Six sessions with Dr.
      Sidman's advanced approach to hypnotherapy resulted in her being free of pain and
      related symptoms for at least 5 years since this intervention. CONCLUSION:
      Resolution of IC symptoms was obtained in a client who had been refractory to
      conventional medical treatment.

PMID- 19769202
TI  - Spontaneous second-trimester uterine rupture in the absence of known risk
      factors: a case report.
AB  - BACKGROUND: Uterine rupture is a rare, catastrophic event in obstetrics. When it
      occurs, it is usually associated with prior uterine surgery, trauma, abnormal
      placentation, or induction of labor. Spontaneous rupture during the second
      trimester is exceptionally rare. CASE: A woman with 3 prior vaginal deliveries
      and no history of uterine surgery, trauma or other risk factors for uterine
      rupture presented at 17 weeks' gestation with vaginal bleeding and an acute
      abdomen. A 5-cm, complete-thickness rupture of the uterine fundus was noted at
      surgery, and the defect was repaired. No abnormalities were noted on the
      pathologic specimen. CONCLUSION: Spontaneous rupture should be considered in
      patients even without risk factors, regardless of gestational age.

PMID- 19769203
TI  - Diagnosis and treatment of vulvodynia.

PMID- 19769205
TI  - Why healing relationships matter in primary care practice.
AB  - Defining a language of relationships in clinical practices challenges health care
      to determine the role of such relationships in achieving patient safety.

PMID- 19769204
TI  - Translating health care-associated urinary tract infection prevention research
      into practice via the bladder bundle.
AB  - BACKGROUND: Catheter-associated urinary tract infection (CAUTI), a frequent
      health care-associated infection (HAI), is a costly and common condition
      resulting in patient discomfort, activity restriction, and hospital discharge
      delays. The Centers for Medicare & Medicaid Services (CMS) no longer reimburses
      hospitals for the extra cost of caring for patients who develop CAUTI. The
      Michigan Health and Hospital Association (MHA) Keystone Center for Patient Safety
      & Quality has initiated a statewide initiative, MHA Keystone HAI, to help
      ameliorate the burden of disease associated with indwelling catheterization. In
      addition, a long-term research project is being conducted to evaluate the current
      initiative and to identify practical strategies to ensure the effective use of
      proven infection prevention and patient safety practices. OVERVIEW OF THE BLADDER
      BUNDLE INITIATIVE IN MICHIGAN: The bladder bundle as conceived by MHA Keystone
      HAI focuses on preventing CAUTI by optimizing the use of urinary catheters with a
      specific emphasis on continual assessment and catheter removal as soon as
      possible, especially for patients without a clear indication. COLLABORATION
      BETWEEN RESEARChERS AND STATE WIDE PATIENT SAFETY ORGANIZATIONS: A synergistic
      collaboration between patient safety researchers and a statewide patient safety
      organization is aimed at identifying effective strategies to move evidence from
      peer-reviewed literature to the bedside. Practical strategies that facilitate
      implementation of the bundle will be developed and tested using mixed
      quantitative and qualitative methods. DISCUSSION: Simply disseminating scientific
      evidence is often ineffective in changing clinical practice. Therefore, learning
      how to implement these findings is critically important to promoting high-quality
      care and a safe health care environment.

PMID- 19769206
TI  - How improving practice relationships among clinicians and nonclinicians can
      improve quality in primary care.
AB  - BACKGROUND: Understanding the role of relationships health care organizations
      (HCOs) offers opportunities for shaping health care delivery. When quality is
      treated as a property arising from the relationships within HCOs, then different
      contributors of quality can be investigated and more effective strategies for
      improvement can be developed. METHODS: Data were drawn from four large National
      Institutes of Health (NIH)-funded studies, and an iterative analytic strategy and
      a grounded theory approach were used to understand the characteristics of
      relationships within primary care practices. This multimethod approach amassed
      rich and comparable data sets in all four studies, which were all aimed at
      primary care practice improvement. The broad range of data included direct
      observation of practices during work activities and of patient-clinician
      interactions, in-depth interviews with physicians and other key staff members,
      surveys, structured checklists of office environments, and chart reviews.
      Analyses focused on characteristics of relationships in practices that exhibited
      a range of success in achieving practice improvement. Complex adaptive systems
      theory informed these analyses. FINDINGS: Trust, mindfulness, heedfulness,
      respectful interaction, diversity, social/task relatedness, and rich/lean
      communication were identified as important in practice improvement. A model of
      practice relationships was developed to describe how these characteristics work
      together and interact with reflection, sensemaking, and learning to influence
      practice-level quality outcomes. DISCUSSION: Although this model of practice
      relationships was developed from data collected in primary care practices, which
      differ from other HCOs in some important ways, the ideas that quality is emergent
      and that relationships influence quality of care are universally important for
      all HCOs and all medical specialties.

PMID- 19769207
TI  - Dropping the baton during the handoff from emergency department to primary care:
      pediatric asthma continuity errors.
AB  - BACKGROUND: The handoff of patient care from emergent to primary care physicians
      (PCPs) has been associated with critical safety problems, especially for children
      with chronic diseases. Continuity-of-information (COI) errors occur when relevant
      information is not transmitted effectively. Follow-up errors occur when a
      recommended visit or telephone contact does not take place when prescribed. A
      study was undertaken to assess the COI and follow-up between a tertiary care
      pediatric emergency department (ED) and PCPs for pediatric patients seeking acute
      asthma treatment. METHODS: Paper charts were reviewed for evidence of continuity
      of information and continuity of follow-up within the directed five-day period
      after an asthma exacerbation as recommended in national guidelines. RESULTS:
      Three-hundred fifty pediatric ED visits for asthma by patients attending these
      community health centers were identified. In 132 (37.7%) of the records, there
      was no evidence of the patient's ED visit in the record (faxed ED discharge note
      or handwritten note by provider). In 219 (62.6%), the faxed ED note and/or
      provider note was present. Illegibility did not contribute to COI errors. There
      was no recorded contact between patients and PCPs in 218 (62.3%) of the charts,
      and 11 (3.1%) indicated appointments were scheduled but missed. Follow-up was
      documented in the remaining 121 (34.6%) charts--109 (31.1%) in clinic and 12
      (3.4%) by phone follow-up. DISCUSSION: More often than not, PCPs appeared to not
      know that their patients sought medical care in the ED for asthma exacerbations.
      The majority of patients did not follow up with their providers. More
      electronically automated and reliable ways of sharing information may diminish
      COI and follow-up errors and thereby improve patient safety.

PMID- 19769209
TI  - The five biggest lies in the health care debate.

PMID- 19769210
TI  - Studies illustrate centrality of family to nursing's perspective.

PMID- 19769208
TI  - Rapid response systems in adult academic medical centers.
AB  - A survey suggests that the academic medical centers with successful rapid
      response system programs defined each call as a chance to save a life, as well as
      an educational opportunity to increase the knowledge of nurses, interns, and
      residents throughout the institution.

PMID- 19769211
TI  - Caregiving burden, acculturation, familism, and Mexican American elders' use of
      home care services.
AB  - Caregiving burden has been shown to predict use of home care services among Anglo
      Americans. In a previous study, only one of two dimensions of caregiving burden
      predicted such use among Mexican American caregivers. Because acculturation and
      familism may affect burden, we conducted analyses to test three hypotheses:
      increased acculturation decreases familism; decreased familism increases burden;
      and increased burden increases use of home care services. Among 140 Mexican
      American family caregivers, acculturation was positively correlated with
      familism; familism was not significantly correlated with burden; objective burden
      was positively correlated with use of home care services, and objective and
      subjective burden significantly interacted in their effect on the use of home
      care services. Targeted interventions may be needed to increase use of home care
      services and preserve the well-being of Mexican American elders and caregivers.

PMID- 19769212
TI  - A model of consequences of dementia caregivers' stress process: influence on
      behavioral symptoms of dementia and caregivers' behavior-related reactions.
AB  - The purpose of this article is to extend the Schultz and Martire Caregiver Stress
      Health Model by explaining consequences of the stress process beyond those
      related to health in dementia caregivers, including consequences for caregivers
      and the dyadic unit, and to highlight the dynamic that exists between caregivers'
      stress, behavioral symptoms of dementia, and behavior-related reactions of
      caregivers. The relevant literature is reviewed, establishing the pervasive
      effects of caregivers' stress within a care dyad. Primary informal caregivers
      play a predominant role in managing environmental stimuli and providing for
      needs, in particular adjusting their own approaches and demeanor to enhance the
      care environment. Thus, behavioral symptoms of dementia and the behavior-related
      reactions of caregivers are conceptualized as a dyadic consequence of the
      caregivers' stress process. This model presents an extended view of the
      consequences of caregivers' stress and provides a more holistic, dyadic approach
      to the issues these vulnerable dyads face. Behavioral symptoms of dementia and
      behavior-related reactions are seen as amenable to caregiver- or dyad-directed
      interventions that target stress reduction. This conceptualization may provide
      support for research, clinical, or policy initiatives that include caregiver
      directed or dyadic interventions for these important behavior-related outcomes.

PMID- 19769213
TI  - Using an existing data set to answer new research questions: a methodological
      review.
AB  - The vast majority of the research methods literature assumes that the researcher
      designs the study subsequent to determining research questions. This assumption
      is not met for the many researchers involved in secondary data analysis.
      Researchers doing secondary data analysis need not only understand research
      concepts related to designing a new study, but additionally must be aware of
      challenges specific to conducting research using an existing data set. Techniques
      are discussed to determine if secondary data analysis is appropriate. Suggestions
      are offered on how to best identify, obtain, and evaluate a data set; refine
      research questions; manage data; calculate power; and report results. Examples
      from nursing research are provided. If an existing data set is suitable for
      answering a new research question, then a secondary analysis is preferable since
      it can be completed in less time, for less money, and with far lower risks to
      subjects. The researcher must carefully consider if the existing data set's
      available power and data quality are adequate to answer the proposed research
      questions.

PMID- 19769214
TI  - Symbolic interactionism and nurse-mother communication in the neonatal intensive
      care unit.
AB  - The admission of an infant to the neonatal intensive care unit (NICU) has the
      potential to cause significant stress for the mothers of these infants.
      Researchers have found that nurse-mother communication has the potential to
      either aid or hinder the mother's adaptation to the NICU environment. These
      communication patterns are relatively complex in nature and therefore warrant
      further investigation. Symbolic interactionism (SI) is a theoretical framework
      that offers the potential to direct such an investigation. The purpose of this
      article is to examine nurse-mother communication patterns in the NICU through the
      theoretical lens of SI.

PMID- 19769215
TI  - A synthesis of the literature on Asian nurses' work experiences in the United
      States.
AB  - Nursing shortages in the United States have underscored the need for foreign
      nurse recruitment. The major population of foreign nurse recruits has long been
      Asian. When employing foreign nurses, fair employment practices and quality of
      care must be ensured; however, few empirical studies were found on this topic.
      Thus, the purpose of this article is to synthesize the extant literature about
      Asian nurses' work experiences in and adaptation to the U.S. health care system.
      The author searched four major bibliographic databases, as well as the ProQuest
      Dissertation and Thesis Database and analyzed eight empirical studies based on
      four predetermined inclusion criteria. The major themes identified in the
      selected scholarly works were: (a) overcoming language barriers, (b) dealing with
      discrimination, (c) adopting U.S. nursing practices, (d) adjusting to U.S. social
      customs, (e) becoming accustomed to U.S. culture, and (f) reconciling work
      ethics. Additional research studies, using both quantitative and qualitative
      approaches, are necessary to gain in-depth knowledge related to this phenomenon.

PMID- 19769216
TI  - A shot at cancer.

PMID- 19769217
TI  - Edible cotton.

PMID- 19769218
TI  - Pink brain, blue brain. Claims of sex differences fall apart.

PMID- 19769219
TI  - See baby discriminate. Kids as young as 6 months judge others based on skin
      color. What's a parent to do?

PMID- 19769220
TI  - Mont. hears suicide case. Treasure State could be third to allow doc assistance.

PMID- 19769221
TI  - Drive this bus into a ditch. What the country really needs right now is a large
      dose of straight talk.

PMID- 19769222
TI  - Making accommodations. Award-winning designs take approaches that benefit
      patients, family and staff.

PMID- 19769223
TI  - Citation/unbuilt. Cleveland Clinic Abu Dhabi, United Arab Emirates.

PMID- 19769224
TI  - Citation/built. Miller Family Pavilion and Glickman Tower, Cleveland.

PMID- 19769225
TI  - Citation/built. SSM St. Clare Health Center, St. Louis County, Mo.

PMID- 19769226
TI  - System overload. Rising demand at clinics straining resources.

PMID- 19769227
TI  - Prevalence of attention deficit disorder among preschool age children.
AB  - Attention deficit hyperactivity disorder (ADHD) is one of the most common
      childhood onset psychiatric disorders. Although the onset of ADHD is prior to the
      age of seven years, there is a paucity of data on the prevalence of the disorder
      in preschool age children. This study was performed to determine the prevalence
      rate of ADHD in preschool age children in kindergartens of south west, Mumbai.
      One thousand two hundred fifty (599 males and 651 females) children aged between
      4-6 years, were selected from 40 kindergartens in 6 localities in south west
      Mumbai. The Conner's index questionnaire was completed for each child by teachers
      and parents. Parents of children whose scores were positive for ADHD (>15) were
      interviewed by a psychiatrist and the ADHD was diagnosed based on DSM-IV criteria
      Schedule for affective disorders. One hundred fifty two (12.2%) children were
      diagnosed to have ADHD. The prevalence of ADHD in preschool age school in south
      west of Mumbai is consistent with previous studies in other countries. This study
      recommends the need for diagnosis and treatment of ADHD in preschool age
      children.

PMID- 19769228
TI  - Management of urethral strictures and their outcome.
AB  - Urethral stricture is a challenging surgical problem since the ancient time. Its
      outcome is very poor because of the high recurrence rate 40.0-50.0% whatever
      procedure is conducted to treat the condition. Between January 2004 to December
      2007, 61 cases with urethral stricture were treated in our hospital. Management
      of stricture was decided according to the grading of urethral stricture. Of 61
      cases, 42 (68.8%) had grade I-II, 10 (16.4%) had grade III and 9 (14.8%) had
      grade IV strictures. They were treated with optical internal urethrotomy (OIU),
      modified railroading and end to end anastomotic urethroplasty respective to
      gradings. During the average 2 years follow up period, outcome of strictures were
      analyzed. Recurrence of stricture was noted 31.0% in grade I-II after OIU and
      11.0% in grade IV after urethroplasty. However, in cases with grade III stricture
      recurrence rate was observed in 60.0% after modified railroading. During the
      follow up period, 50.0% of the grade III strictures were converted to
      urethroplasty. It is suggested that, OIU is still a gold standard procedure to
      manage the lower grade (I-II) strictures with low morbidity, minimally invasive
      and success rate is 69.0%. End to end anastomotic urethroplasty for grade IV
      stricture has very good result (89.0%) but needs skilful mobilization of distal
      urethra to prevent chordee. However, grade III stricture needs open urethroplasty
      or modified railroading by using flexible cystoscopy which may reduce recurrence
      rate.

PMID- 19769229
TI  - Method for detecting circulating Toxocara canis antigen and its application in
      human serum samples.
AB  - Diagnosis of larval migrans (LM) is usually done by immunodiagnostic methods.
      These methods, however, simply show the presence or absence of antibody but not
      the active infection of the patients. Therefore, we aimed to establish a
      diagnostic method for detecting circulating Toxocara canis antigen using a
      sandwich, ELISA. Monoclonal antibodies (MAb) were produced against the excretory
      secretory (ES) antigen of second-stage T canis larvae. Among the MAbs obtained,
      we selected one MAb (TCMAb12; molecular weight, 30-80 kDa, IgG) for use in the
      sandwich ELISA. The cross-reactivity of the sandwich-ELISA against thirteen
      different kinds of parasite antigens were examined. The results revealed that the
      antibody reacted with T canis ES antigen, T. canis female antigen, and T. canis
      second-stage larvae antigen, but did not react with any other antigens. From
      results obtained using an ES antigen concentration standard curve, we confirmed
      that the detection limit of the sandwich-ELISA was 5 ng/ml, which provides
      sufficient sensitivity for the diagnosis of toxocariasis (LM). We applied the
      method to suspected toxocariasis patients and examined the circulating antigen in
      their sera. We used nine serum samples collected from patients with suspected
      toxocariasis based on both their clinical symptoms and high antibody titers.
      Overall, five sera showed antigen-positive reactions, while the remaining four
      were negative. These results indicated that about 44.0% of the antibody-positive
      patients were antigen-negative, not ongoing active infection. The results
      obtained using this technique would provide us for understanding toxocariasis.

PMID- 19769230
TI  - Echocardiography based cardiac evaluation in the patients suffering from chronic
      obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) is the most common medical problem
      in Nepal. Echocardiography based cardiac evaluation in COPD is rare in Nepal. The
      purpose of this study is to evaluate the echocardiography based cardiac function
      in consecutively admitted COPD patients (507) in medical wards of Nepal Medical
      College Teaching Hospital during 13th April 2007 to 12th April 2008. Male female
      ratio was 0.9:1. Age (mean +/- SD) was 66.1 +/- 10.9 yr. Brahman and Chhetri
      ethnic group comprised of more than half of total COPD patients followed by
      similar number of patients in Newar (22.1%) and Mongolian ethnic groups (21.5%).
      More than half of the COPD patients were in age group 60-75 years, followed by
      less number of patients (approximately 20.0%) in both 45-59 years and 75-89 years
      age groups. Of the total patients (507), 141 patients underwent echocardiographic
      evaluation. Among them significant number of patients had poor LVEF (29, 20.6%)
      with statistically significant difference in LVEF (36.0 +/- 10.5 vs. 64.3 +/-
      8.5%, p value < 0.01). More than half of the total patients showed features of
      chronic cor pulmonale (56.3%), followed by valvular heart disease (49.3%),
      diastolic dysfunction (38.7%) and left ventricular hypertrophy (14.1%). Mild
      pulmonary artery hypertension (PAH) was detected in approximately half of
      patients (49.1%), followed by moderate PAH in 17.6% patients. Transthoracic
      echocardiography was found to be very useful to identify various concomitant
      cardiac abnormalities demanding special treatment consideration in managing
      clinically COPD like patients.

PMID- 19769231
TI  - Change in refractive status of the patients undergoing phacoemulsification
      surgery.
AB  - This study was carried out with the objective of finding refractive status of
      patients undergoing phacoemulsification surgery for cataract extraction. Success
      of cataract surgery can be quantified with the improvement in visual acuity with
      least amount of refractive error. Prospective study of 44 patients was done pre
      operatively and with subsequent follow up in the first, third and eighth week
      post operatively. Pre and post operative evaluation was carried out in terms of
      visual acuity, refractive error and corneal curvature. Among patients undergoing
      surgery, 91.0% achieved visual acuity of 6/9 or better at eighth week follow up
      73.3% of patients had astigmatism of 1.25 dioptric cylinder or less. Keratometry
      readings showed insignificant variability in the preoperative and postoperative
      period (p > 0.05). This confirms that phacoemulsification surgery does not change
      the corneal curvature significantly and thereby induces less amount of
      astigmatism.

PMID- 19769232
TI  - Comparative evaluation of microscopy and polymerase chain reaction (PCR) for the
      diagnosis in suspected malaria patients of Nepal.
AB  - Microscopy has been the most common technique for the diagnosis of malaria in
      Nepal. This study was undertaken at CDM, TU, Kathmandu, and Department of
      Clinical Tropical Medicine, Mahidol University, Bangkok to compare the efficiency
      of microscopy and PCR for malaria diagnosis in Nepalese context. During July
      August 2007, blood samples were collected in glass slides and on filter papers
      from suspected malaria cases of Kanchanpur, Jhapa and Morang Districts. Sample
      transportation and storage was done using standard protocol. Microscopy was done
      at the heath posts in the district in Nepal while Nested PCR using previously
      standardized primers was carried out at Mahidol University. Among 824 malaria
      suspected cases, 19.2% (157) were laboratory confirmed as malaria cases (P. vivax
      10.9%, P. falciparium 7.7% and 0.4% were of mixed infection) by microscopy. The
      parasite count range was detected as 320-25020 parasites/microl. Among total 132
      samples (114 microscopic positive, 18 negative) were processed for nested PCR.
      Among microscopic positive samples with increase of the parasitaemia/microl of
      the blood, the rate of detection by PCR (75.4%) was increased though the PCR
      failed to detect 2 cases having the parasitaemia 5000-15000/microl of blood
      however 4 microscopic negative cases were detected as P. vivax infection. Among
      the microscopy positive samples for P. falciparum, 3 were found P. vivax and 2
      were found as mixed infection of Pv and Pf and 6 P. vivax were found positive for
      P. falciparum by PCR. Two microscopy positive samples for mixed infection were
      found be positive for one Pv and one Pf by PCR. PCR could be good tool in
      confirming the clinically strongly suspected but microscopically negative malaria
      cases and advanced molecular epidemiological studies, although its use in routine
      diagnosis may not be feasible.

PMID- 19769233
TI  - Delirium at Nepal Medical College Teaching Hospital: reason for referral and
      subtypes.
AB  - The important neuropsychiatric disorder delirium is the most single important
      disorder in onsultation liaison psychiatry. There is a dearth of study in
      delirium. The purpose of this study was to find out the demographic profile,
      reason for referral, and subtypes of delirium. Thirty two consecutive cases of
      delirium diagnosed by psychiatrist in consultation liaison psychiatry were
      enrolled in the study. This is a descriptive study and diagnoses were made based
      upon 'The International Classification of Disease (ICD-10)'. The majority of
      cases were from age 70 and above, male sex being more common and most commononest
      reason for referral being disturbed behavior. The hyperactive subtype of delirium
      was the frequent finding. Medicine and ICU followed by surgery and post operative
      ward were the most referring departments.

PMID- 19769234
TI  - Metabolic syndrome among inmates of a 'home for aged' using IDF 2005 criteria.
AB  - To identify the metabolic syndrome (MetS) among inmates of a 'home for aged'
      using IDF 2005 criteria. 100 subjects from inmates of a 'home for aged' studied
      for the identification of metabolic syndrome using International Diabetes
      Federation (IDF) 2005 criteria. Presence of waist circumference (WC) (Men > or
      =90 cm, Women > or =80 cm) plus any two of the following four factors;
      triglycerides (TG) >150 mg/dl (1.7 mmol/l), (II) HDL-Cholesterol (HDL-C) <40
      mg/dl (1.0 mmol/l) for men, <50 mg/dl (1.3 mmol/l) for women, fasting plasma
      glucose (FPG) > or =100 mg/dl (6.1 mmol/l) and blood pressure (BP) > or = 130/85
      mm of Hg. Indicated the MetS. MetS was present in 57.0%. WC was common component,
      TG was increased in 71.9%, low HDL-C present in 86.0%, raised FPG present in
      66.7% and hypertension in 45.6%. MetS was more common in older women than in men
      (63.6% vs. 48.8%) and decreased HDL-C is core components of the MetS in this
      population. High calorie diet and sedentary life style may be contributing
      factors of MetS in this population. MetS is common in elderly subjects. It is age
      related, and is more common in elderly women.

PMID- 19769235
TI  - Prevalence and determinants of diabetes among the elderly population in the
      Kathmandu Valley of Nepal.
AB  - Elderly populations are susceptible to many non-communicable diseases, including
      diabetes. Lack of awareness regarding disease status and risk factors increase
      complications and mortality. We conducted a cross-sectional community-based study
      of 1633 randomly selected participants aged 60 years and above in urban and rural
      areas in the Kathmandu Valley of Nepal. Study goals were: (i) to determine the
      prevalence of diabetes in elderly subjects as diagnosed prior to and during the
      study, and (ii) to identify and compare the determinants of diabetes as diagnosed
      prior to and during the study. A structured questionnaire was used to collect
      information regarding prevalence and potential determinants of diabetes diagnosed
      during and before the survey. Anthropometric measurements, blood pressure
      measurements and fasting blood sugar tests were also measured. Risk factor
      analysis was done using multinomial logistic regression; subjects with no
      diabetes constituted the reference group. We detected an overall diabetes
      prevalence of 25.9%, 17.3% diagnosed during the survey and 8.6% previously
      diagnosed. Age, disturbed sleep, and family history of hypertension were
      marginally significantly (p < 0.10) associated with diabetes diagnosed in the
      survey. In contrast, education, exercise, health perception, family history of
      hypertension, having a caretaker at night, receiving help from friends when
      seeking health care and mean waist circumference were significantly (p pounds
      0.05) or marginally associated with diabetes detected before the survey. The high
      prevalence of diabetes in the elderly population studied, and the low level of
      prior diagnosis, identify an important public health problem. There is a need for
      improved screening of diabetes and improved health care and education in the
      elderly. There is also need for better understanding of risk factors associated
      with previously undiagnosed diabetes.

PMID- 19769236
TI  - Dialysis access pattern in incident haemodialysis patients at B & B Hospital,
      Kathmandu, Nepal.
AB  - The clinical practice guideline for vascular access in haemodialysis recommends
      the use of arteriovenous fistula (AVF) over a central venous catheter. AVF needs
      to be created sufficiently in advance of anticipated haemodialysis. However, many
      incident haemodialysis patients are still being dialyzed with central venous
      catheter at the time of first haemodialysis. This paper aims at presenting the
      pattern of dialysis vascular access in incident haemodialysis patients at our
      institution from July 2002 to July 2008 in a cohort of patients who were referred
      to us for creation of native AVF. A total of 100 patients (56 male and 44 female)
      with the mean age of 54 years were studied. Only 110.0% of patients were found to
      have AVF created in advance and the rest (89.0%) were dialyzed via central venous
      catheter. Of the 11 patients with AVF; 5 fistulas were created 3 months prior to
      the dialysis, 3 fistulas between 1 and 3 months prior and 3 less than a month of
      anticipated dialysis. Interestingly, 35.0% of total patients were seen by
      nephrologists only a month prior to the dialysis. Hence, an early referral of the
      chronic renal failure patients to the nephrologists and vascular access surgeons
      may overcome this problem.

PMID- 19769237
TI  - Detection of tubal abnormalities by HSG in Nepalese subfertile women.
AB  - Fallopian tube defects are responsible for subfertility in 12.0-33.0% of
      subfertile couple. Hysterosalpingography (HSG) is a safe and less invasive method
      of detecting both the tubal and uterine defects. The objective of this study was
      to find out the incidence of tubal blockage including its site and side diagnosed
      by HSG in subfertile Nepalese women and to find out the incidence of uterine and
      other abnormalities detected by this test. This was a prospective study of 1000
      cases of subfertility, conducted in Om Hospital, Kathmandu. A short history and
      HSG report of these cases were obtained from the Radiology department of the
      hospital. Size and shape of the uterine cavity, evidence of cervical
      incompetence, tubal visualization, spillage of dye, tubal block with its side and
      site, evidence of peritoneal adhesion and intravasation of dye in vessels were
      noted. Quick spillage of the dye in the peritoneal cavity or spillage only after
      pushing the dye with pressure was also noted. Results were entered in simple
      tabulations and analyzed. Among 1000 cases, 65.8% had primary and 34.2% had
      secondary subfertility. 29.0% of the total 1000 cases had abnormal HSG findings.
      19.0% of total 1000 cases had tubal blockage. Incidence of tubal blockage in both
      primary (19.1%) and secondary subfertilty (18.7%) was almost same, in contrary to
      previous belief. Mullerian defect was present in 3.2% of primary subfertility and
      2.0% of secondary subfertility cases. Cervical incompetence was not detected in
      any case. Evidence of uterine infection was present in 0.7% of primary
      subfertility and 0.2% of secondary subfertility cases. Abnormal size of uterine
      cavity was present in 1.2% of primary subfertility and 0.5% of secondary
      subfertility. Features of phimosis of fimbrial opening, localized spill and
      intravasation of dye were present respectively in 5.6%, 1.5%, 1.2% in primary
      subfertility and 4.9%, 1.7% and 1.7% in secondary subfertility.In conclusion; the
      incidence of tubal blockage detectable by HSG in this study was 19.0%.

PMID- 19769238
TI  - Outcome of probing under topical anesthesia in children below 18 months of age
      with congenital nasolacrimal duct obstruction.
AB  - Congenital Nasolacrimal Duct Obstruction (CNLDO) is one of the commonest causes
      of Childhood epiphora. This study was carried outat Sagarmatha Chaudhary Eye
      Hospital (SCEH), Lahan to determine the success rate of probing and syringing in
      children below 18 months of age with CNLDO. A hospital based prospective
      interventional study of 106 children with age 4 to 18 months (Mean 7.67, SD 4.37)
      who underwent probing and syringing under topical anesthesia in minor procedure
      room of OPD. The children were divided into 3 age groups, Group A (age d" 6
      months), Group B (age = 7-12 months) and Group C (age = 13-18 months). Success of
      probing was defined as complete relief of signs and symptoms on follow up at 3-6
      weeks. Out of 106 children with CNLDO below 18 months of age, 97 (91.5%) children
      had better outcome with first attempt of probing. First attempt of probing
      resulted in resolution in 92.3% (108 out of 117) eyes; 95.6%, 92.7%, 87.1% in the
      age group less than 6 months, 7-12 and 13-18 months respectively. 9 eyes
      underwent a repeat procedure of which 6 eyes were cured. Probing and syringing
      below 6 months of life has shown to be very effective with almost 100% success.
      The overall success of probing and syringing among children less than 18 months
      was 97.4%.

PMID- 19769239
TI  - Failure of subarachnoid block in caesarean section.
AB  - Subarachnoid block is the most convenient and safe anaesthesia during caesarean
      section. But there are incidences where subarachnoid block does not work and
      other methods of anaesthesia have to be employed. This study was done in 2039
      female patients who underwent caesarean Section at Paropakar Maternity and
      Women's Hospital, Thapathali, Kathmandu Nepal from 1st October 2005 to end of
      September 2006 to find the rate of failure of subarachnoid block in Caesarean
      Section and look for the causes of failure. Patients of age 17 years to 43 years
      (mean age 25.40 years) and ASA I and II were included in the study. Spinal needle
      (Sprotte) of 26 Gauze with Quincke's bevel was used. Solution injected was 2.20
      ml of 0.5% hyperbaric Bupivacaine. Of the total 2039 patients who received
      subarachnoid block with the above mentioned methods, 6.0% (n=123) needed further
      anesthetic agents. Conversion to general anesthesia was needed in 87 (4.3%)
      patients. Rest 1.8% (n=36) could be operated with further administration of
      intravenous agents (Ketamine, Diazepam and/or Pentazocine) only.

PMID- 19769240
TI  - A study of wasp bites in a tertiary hospital of western Nepal.
AB  - Hymenopterid stings and subsequent allergic reactions including fatal anaphylaxis
      are common indications for emergency department visits worldwide. Besides that,
      sting can cause death as a result of multi-system involvement ranging from
      intravascular hemolysis, rhabdomyolysis, acute renal failure, hepatic dysfunction
      and occasionally thrombocytopenia and coagulopathy. Eleven cases (all male, age
      35.5 +/- 15.2 years) of wasp bites admitted in the Manipal Teaching Hospital
      (MTH), Pokhara during 01st February, 2006 to 30th October, 2007 were enrolled in
      this study. Mean wasp bites number was 48.7 +/- 7.1 (11-100) and mean time to
      reach the hospital from the bite time was 69.1 +/- 149.7 hours (1.5 h-12 days).
      Nine patients developed acute renal failure (ARF) and secondary hypertension.
      Eight patients underwent hemodialysis. Two patients stuck by more than 75 stings
      developed refractory pulmonary edema and died in the course of treatment. Victims
      with lesser numbers of wasp envenomation, who received quick initiation of
      alkaline diuresis and intensive dialytic support had shorter hospital stay and
      less severe complications.

PMID- 19769241
TI  - Comparative study of post term and term pregnancy in Nepal Medical College
      Teaching Hospital (NMCTH).
AB  - Post term pregnancy (PTP) is one of the commonest obstetric conditions. Pregnancy
      is called term when it lies between 37 completed weeks to 42 completed weeks (259
      to 294 days) from the last menstrual period. If the pregnancy exceeds this period
      (above 42 completed weeks) it is classified as post term pregnancy. The over all
      incidence of PTP is 10.0% of all pregnancies. The incidence of PTP varies
      depending on whether the calculation is based on the history and clinical
      examination alone, or whether early pregnancy ultrasound examination is used to
      estimate gestational age. Because of increased risk of maternal and perinatal
      morbidity and mortality, it is taken as high risk pregnancy. The published data
      on risk of unexplained intrauterine death associated with PTP vary. It is mostly
      due to decrease in amniotic fluid volume; meconium passed in utero, placental
      changes like calcification, abruption placentae and big baby. In present study
      the prevalence of PTP is 4.6% which is much less than those in different studies.
      Maternal and neonatal outcomes of pregnancy and related complications were
      compared with normal term pregnancy. This comparative study revealed increased
      risk to mother and fetus as pregnancy advances beyond term.

PMID- 19769242
TI  - In-center hemodialysis for end stage kidney disease at Nepal Medical College and
      Teaching Hospital.
AB  - End stage kidney disease (ESKD) is defined by glomerular filtration rate (GFR)
      less than 5 ml/min. These patients need renal replacement therapy (RRT).
      Hemodialysis is an established form of RRT. Studies on incenter hemodialysis are
      very few. Here we would like to present our experience on in-center hemodialysis
      in Nepal Medical College and Teaching Hospital. Study period was one year (1st
      Baisakh 2065 to 31st Chaitra 2065). Total 33 patients (23 male, 10 female) were
      enrolled in the study. Average age was 42.33 +/- 15 years. Hypertension (55.0%),
      diabetes mellitus (24.0%), chronic glomerulonephritis (15.0%), rapidly
      progressive glomerulonephritis (3.0%) and others (3.0%) were the causes of ESKD
      requiring dialysis. Hypotension, hypertension, muscle cramps, chest pain were the
      common complications observed during dialysis. Average haemoglobin level was 9.44
      +/- 1.88 g%. Majority of patients were physically inactive. Blood transfusion was
      the main modality for correction of anaemia. Approximate cost for one session of
      hemodialysis was Rs. 2000 (U.S. $.25) and average monthly income of study
      population was Rs.16312.5 (U.S. $.204) U.S. $1 = NRs.80, (4th May 2009).

PMID- 19769243
TI  - Diagnosis and management of cervical ectopic pregnancy--report of three cases.
AB  - Cervical pregnancy is a rare variety of ectopic gestation. The etiology is
      obscure. Diagnosis may be difficult unless the clinician/the radiologist are
      conscious of the entity.

PMID- 19769244
TI  - Live birth following treatment of post molar choriocarcinoma.
AB  - A G3P(1+1) who underwent dilatation and curettage (D and C) for persistent
      vaginal bleeding after a month of molar evacuation, underwent successful
      treatment of choriocarcinoma with methotrexate and was able to have normal baby
      weighing 2800 gms with good Apgar score and normal placenta. This shows that a
      normal menstruation and uncomplicated term delivery can be expected after
      complete chemotherapy for gestational trophoblastic neoplasia (GTN).

PMID- 19769245
TI  - Variation in relation of cords of brachial plexus and their branches with
      axillary and brachial arteries--a case report.
AB  - Anatomical variations in the formation, course and distribution of brachial
      plexus are well documented. The present report describes some rare variations
      with regard to relation of cords of brachial plexus, median and ulnar nerves with
      the third part of axillary artery and brachial artery in the left upper limb of
      an adult male cadaver. All three cords of brachial plexus were noted to be
      lateral to all three parts of axillary artery. Median nerve was lateral to
      brachial artery and ulnar nerve was between the brachial artery and median nerve.
      Further distribution of median and ulnar nerves was normal. The arterial pattern
      in left arm (axillary and brachial arteries) was also normal. The findings were
      noted after thorough and meticulous dissection of both the upper limbs (axilla,
      arm, cubital fossa, forearm and palm) of the same cadaver in the Department of
      Anatomy, College of Medical Sciences, Bharatpur, Nepal. The right upper limb
      revealed no abnormality. It is important to be aware of such variations while
      planning a surgery in the region of axilla and arm as these nerves are more
      liable to be injured during surgical procedures. Possible embryological
      explanations and clinical significance have been discussed.

PMID- 19769246
TI  - Eccrine poroma in neck of a child--a rare presentation.
AB  - An eccrine poroma is a common benign tumour arising from the eccrine sweat gland
      duct epithelium in the dermo-epidermal region. Its occurrence in the neck region
      in pediatric age group is a rare entity. Here we report a case of an eccrine
      poroma in the retro-auricular area just below and behind the lobule of the left
      pinna in a nine years old child.

PMID- 19769247
TI  - [Reference value of periapical film in diagnosis of intractable odontopathy].
AB  - Periapical film is one of important method for odontiasis diagnose. The
      periapical film can reflect some changes in root tip or periapical tissue found
      under human observation hardly. Those changes take great effect in diagnose of
      intractable odontopathy. The various kinds of appearance in periapical film, such
      as anatomy mutation of root canal, vertical fracture, tooth trauma, root
      absorption, expanding file broken down in root canal should be made a special
      effort and the mutation of normal anatomy tissue should be done too. Computerized
      tomography or panorama film could be used when questionable problem show up on
      the periapical film of intractable case.

PMID- 19769248
TI  - [Heterotopic complex membrane induces bone formation].
AB  - OBJECTIVE: The composite membrane was made by recombinant human bone
      morphogenetic protein-2 (rhBMP-2), collagen (Co), polylactic-co-glycolic acid
      (PLGA). To observe the ectopic bone formation and evaluate the capability of
      rhBMP-2/Co/PLGA complex membrane. METHODS: 48 male Kunming adult mice were
      divided into two groups randomly: Co/PLGA complex membrane group and rhBMP
      2/Co/PLGA complex membrane group. After etherized, an incision was made on the
      outer muscle and two groups of complex membranes were implanted into the right
      side hind limb muscle pouch. 8 mice from each group were sacrificed at 7, 14, 28
      d. The hind limbs were removed, examined by soft X-ray, HE staining and light
      microscope examination. RESULTS: Wounds healed well, no infections and rejections
      were observed. In the Co/PLGA group, partial implanted membrane degradated and
      absorbed at 7 d. The membrane collagen fiber appeared loose at 14 d. The membrane
      lost its intact to disrupted at 28 d. No ectopic bone formation was found. In the
      rhBMP-2/Co/PLGA group, ectopic bone formation was found by eye, soft X-ray and
      histological examinations. The rhBMP-2/Co/PLGA complex membrane degraded slower
      than Co/PLGA complex membrane. CONCLUSION: Co/PLGA can provide a carrier for
      rhBMP-2 to have stronger effect of biological activity.

PMID- 19769249
TI  - [Expression and correlation of mast cell, Clusterin/apoJ and transforming growth
      factor-beta in the different stages of human dermal hemangioma].
AB  - OBJECTIVE: To investigate the expression and correlation of mast cell,
      Clusterin/apoJ and transforming growth factor-beta (TGF-beta) in the different
      stages of human dermal hemangioma. METHODS: Immunohistochemical stain technique
      (SABC) and toluidine blue (TB) stain technique were respectively used to detect
      the expression level of Clusterin/apoJ and TGF-beta and the number of mast cells
      in the different stages of human dermal hemangioma. RESULTS: There was remarkable
      statistical difference between the advanced stage of proliferative hemangioma and
      the other stages of proliferative hemangioma in the number of mast cell(P<0.01).
      There was also remarkable statistical difference between the early stage of
      involutional hemangioma and the other stages of involutional hemangioma in the
      number of mast cell (P<0.01). The expression of Clusterin/apoJ and TGF-beta in
      the advanced stage of proliferative hemangioma was significantly higher than the
      other stages in proliferative hemangioma (P<0.01). The expression of
      Clusterin/apoJ and TGF-beta in the early stage of involutional hemangioma was
      significantly higher than the other stages in involutional hemangioma (P<0.01).
      There was a significantly positive correlation between Clusterin/apoJ and TGF
      beta in the different stages of human dermal hemangioma (P<0.01). The expression
      level of Clusterin/apoJ and TGF-beta was positively correlated with the number of
      mast cell in the different stages of human dermal hemangioma (P<0.01).
      CONCLUSION: Mast cell may play a promotive role of apoptosis during the
      spontaneous regulate the expression of Clusterin/apoJ and promote the spontaneous
      involution of human dermal hemangioma.

PMID- 19769250
TI  - [The effect of Nifedipine and mechanical strain on matrix metalloproteinase
      expression in human periodontal ligament fibroblast].
AB  - OBJECTIVE: To investigate the effect of Nifedipine on matrix metalloproteinase
      (MMP)-10 and MMP-13 expression in human periodontal ligament fibroblast (HPDLF)
      induced by mechanical strain in vitro. METHODS: HPDLF was divided into four
      groups at random by mechanical strain of elongation 0%, 8%, 12% and 16%. Each
      group was divided into four subgroups again by the concentration of Nifedipine 0,
      10, 30, 50 microm. The cells were imposed to state mechanical strain 12 h after
      incubated with Nifedipine 1 h. And then immunohistochemical staining was used to
      investigate the expressions of MMP-10 and MMP-13 in intracytoplasm. RESULTS: In
      0% group, there was no significant difference of MMP-10 and MMP-13 expression in
      all subgroups (P>0.05). The expressions of MMP-10 and MMP-13 were high in group
      8%, 12% and 16% without Nifedipine, and increasing significantly with elongation
      (P<0.001). The expressions of MMP-10 and MMP-13 decreased with dose increasing
      (P<0.001) in HPDLF after imposed to Nifidepine. CONCLUSION: The expressions of
      MMP-10 and MMP-13 induced by mechanical strain were inhibited by Nifedipine,
      which suggested calcium ions channels participate in expressions of MMP-10 and
      MMP-13 induced by loading.

PMID- 19769251
TI  - [Expression of beta-catenin and adenomatous polyposis coli protein and
      correlation between them in the development of mouse tooth germ].
AB  - OBJECTIVE: To examine the distributions of beta-catenin and adenomatous polyposis
      coli (APC) protein in the tooth germ, and obtain the messages of function of the
      two factors and the relationship between them. METHODS: Mice were selected and
      cohabited with the ratio of female mice to male ones being 2:1, and Embryo day
      0.5 was confirmed based on the finding of vaginal plug. The distributions of beta
      catenin and APC protein in the Embryos on day 13.5, 14.5, 15.5, 16.5, 17.5 were
      examined in the paraffin-embedded sections by immunohistochemistry methods.
      RESULTS: During E13.5 d to E17.5 d, positive expression of beta-catenin was found
      in the oral epithelium and the dental lamina, and became more and more strong.
      The staining were whole cell. During the bud stage, strong positive expression of
      APC protein was found in the oral epithelium and the dental lamina, but the
      expression displayed a down-regulation tendency. The staining was the
      cytomembrane and cytoplasm. There was negative correlation between beta-catenin
      and APC protein (P<0.01). CONCLUSION: The result of beta-catenin suggests its
      contribution in the early development of enamel organ and the proliferation of
      cell. Coincidance of the two factors staining site was found, according to the
      statistics.

PMID- 19769252
TI  - [Effect of Celecoxib on cycloxygenase-2 expression and inducing apoptosis in
      Tca8113 cell lines].
AB  - OBJECTIVE: To observe whether Celecoxib could inhibit the growth, regulate the
      expression of COX-2 and induce apoptosis of Tca8113 cells. METHODS: Tca8113 cells
      were incubated with different concentrations of Celecoxib for 24, 48 and 72 h,
      and MTT was used to calculate growth inhibition rate. The expression of COX-2
      protein and mRNA in Tca8113 cells was detected with SP immunohistochemistry
      staining and fluorescent quantitative real-time RT-PCR. Morphology of apoptosis
      cells was observed by fluorescence microscopy, and Annexin V-FITC/PI double
      labeling method was employed to detect early stage cell apoptosis. RESULTS: COX-2
      protein was strongly expressed in Tca8113 cells and was suppressed by Celecoxib.
      The growth and proliferation of Tca8113 cells treated with Celecoxib were
      inhibited in a dose-dependent manner. Celecoxib treatment resulted in significant
      increase in apoptosis and early apoptotic rate. Fluorescent quantitative real
      time RT-PCR results showed no significant effet on regulating expression of COX-2
      mRNA. CONCLUSION: Celecoxib shows a significant effect on inhibiting expression
      of COX-2 in Tca8113 cells, this is probably related to growth inhibition and
      inducing apoptosis of Tca8113 cells.

PMID- 19769253
TI  - [Effects of tumor necrosis factor-alpha on the growth of rat osteoblasts].
AB  - OBJECTIVE: To investigate the effects of tumor necrosis factor alpha (TNF-alpha)
      on the growth of rat osteoblasts. To find out the mechanisms that TNF-alpha
      regulates the growth of osteoblasts. METHODS: To assay osteoblasts proliferation
      by MTT. To assay alkaline phosphatase (ALP) activity of osteoblasts by PP
      nitrophenyl phosphate (PNPP). RESULTS: The osteblasts proliferation and the ALP
      activity decreased in treatment groups, and the significantly lower levels were
      observed in above 50 ng/mL groups (P<0.05). CONCLUSION: TNF-alpha restrained
      osteoblasts proliferation and differentiation, and the effects were more
      significant in above 50 ng/mL groups.

PMID- 19769254
TI  - [Response of bone marrow mesenchymal stem cells to mechanical stretch and gene
      expression of transforming growth factor-beta and insulin-like growth factor-II
      under mechanical strain].
AB  - OBJECTIVE: To study the response of rat bone marrow mesenchymal stem cells (MSCs)
      to a single period of mechanical strain and expression patterns of transforming
      growth factor-beta (TGF-beta) and insulin-like growth factor-II (IGF-II) after
      mechanical stretch. METHODS: Bone marrow MSCs were isolated from SD rats and
      cultured in vitro. A four-point bending apparatus were used to perform a single
      period of mechanical strain (2000 microepsilon, 40 min) on MSCs. Cellular
      proliferation and alkaline phosphatase (ALP) activity of MSCs were examined and
      gene expression patterns of TGF-beta and IGF-II were detected by SYBR green
      quantitative real-time RT-PCR. RESULTS: Cell proliferation, ALP activity and
      expression of TGF-beta and IGF-II were all significantly up-regulated in
      stretched MSCs when compared with their controls. The mRNA levels of TGF-beta and
      IGF-II got top increase immediately after mechanical loading and increased about
      51.44 and 8.92 folds, respectively, when compared with control cells. Expression
      of TGF-beta and IGF-II decreased with time and returned to control level at 12 h
      after mechanical stimulus, despite of a small increase at 6 h. CONCLUSION: The
      mechanical stretch can promote MSCs proliferation, up-regulate its ALP activity
      and induce a time-dependent expression increase of TGF-beta and IGF-II which in
      turn result in osteogenic differentiation of MSCs. Mechanical stimulus is a key
      stimulator for osteogenic differentiation of MSCs and vital for bone formation in
      distraction osteogenesis.

PMID- 19769255
TI  - [Influence of luxS of Streptococcus mutans on biofilm of dental plaque].
AB  - OBJECTIVE: To construct luxS mutant aften luxS gene of Streptococcus mutans (S.
      mutans) was knocked out, and examine their ability of biofilm formation. METHODS:
      A recombinant plasmid containing the flanking fragment of luxS of S. mutans was
      transformed into S. mutans UA159, and selected by brain heart infusion (BHI) agar
      medium with kanamicin. The luxS mutant further confirmed via polymerase chain
      reaction (PCR) and the autoinducer-2 (AI-2) bioluminescence assay of Vibrio
      harveyi (V. harveyi), and ability of luxS mutant and S. mutans UA159 biofilm
      formation was examined in different phases, in BHI medium with 1% sucrose and 1%
      glycose by scanning electron microscopy (SEM). RESULTS: LuxS-deficient S. mutans
      strains were successfully constructed. Compared with S. mutans UA159, the luxS
      mutant maintained in BHI medium containing 1% sucrose displayed an apparent
      defect in biofilm formation, while they showed no significant deviation in BHI
      medium containing 1% glycose. CONCLUSION: luxS gene in S.mutans can play a role
      in dental plaque biofilm formation, and the luxS gene is possible to regulate
      sucrose-dependent biofilm formation.

PMID- 19769256
TI  - [Investigation on 2317 working authorizations of fixed partial dentures].
AB  - OBJECTIVE: The aim of the survey was to obtain the basic information of the
      working authorizations of fixed partial dentures so as to enhance the quality of
      professional cooperation between dentists and dental technicians in the future.
      METHODS: 2317 pieces of working authorizations of fixed partial dentures were
      divided into three groups according to the level of consignors. The filling of
      working authorization was recorded. The items in the questionnaire included the
      patients' information (name, gender, age and telephone number), design (design of
      occlusion, bridge, bottom crown, connector, and shade selection), sign and
      product date. RESULTS: The statistical test showed there was significant
      difference in patients' age, telephone number and product date among these three
      groups. Dentists paid more attention to shade selection of anterior teeth than
      posterior teeth. CONCLUSION: In this survey, the filling of working authorization
      of fixed partial dentures is generally ignored by dentists. The filling of
      working authorization should be strengthened.

PMID- 19769257
TI  - [Epidemiological survey of dentine hypersensitivity of young people in Chengdu
      City].
AB  - OBJECTIVE: To investigate the prevalence and risk factors of dentine
      hypersensitivity of young people in Chengdu city. METHODS: The dentine
      hypersensitivity of 741 cases aged 18-35 living in Chengdu city were surveyed
      with questionnaire and oral examination by random collection during June to July
      in 2008. The relative risk factors to dentine hypersensitivity were analyzed.
      RESULTS: 128 cases (17.27%) were diagnosed as dentine hypersensitivity. The
      prevalence of dentine hypersensitivity was higher among female than male
      (P<0.01). Cold was the most common stimulus for dentine hypersensitivity
      (62.80%). The most common affected tooth was the right maxillary first premolar
      (15.51%). Acid regurgitation, carbonated beverage, hard toothbrush type and heavy
      toothbrushing force were risk factors to dentine hypersensitivity. CONCLUSION:
      The prevalence of dentine hypersensitivity of Chengdu city's young people is
      widespread. Acid and incorrect toothbrushing methods can cause dentine
      hypersensitivity. The correct protective measure to dentine hypersensitivity
      should be publicized.

PMID- 19769258
TI  - [Influence of different surface roughness of opaque porcelain on reflectance and
      L* value of porcelain fused to metal].
AB  - OBJECTIVE: The purpose of this study was to investigate how different surface
      roughness of opaque porcelain influence reflectance and CIE L* value of porcelain
      fused to metal (PFM) restorations. METHODS: 48 casted Ni-Cr alloy metal specimens
      (12.0 mm x 1.0 mm) were fabricated with ShoFu Vintage Halo porcelain and divided
      into six groups, eight pieces for each group. The specimens in the first group
      without polishing were used as control. Other groups were polished against 200-,
      400-, 600-, 800-, and 1000-grit sandpaper after sintered, respectively. Surface
      roughness and color parameters of the specimens were measured with a Surface
      Roughometer EX2154-13 and a spectrocolorimeter, respectively. Ra (arithmetical
      mean deviation of the profile) was the main standard value to describe the
      surface roughness of many kinds of meatal or porcelain materials, and here we
      used it to express surface roughness of opaque porcelain. The data were
      statistically analyzed by one-way analysis of variance (alpha = 0.05) in SPSS
      13.0. RESULTS: The reflectance value increased from 72.386 +/- 3.953 to 78.671 +/
      3.408, and CIE L* value from 90.189 +/- 1.200 to 93.496 +/- 1.070 with the
      increasing of surface roughness (Ra) of opaque porcelain from (0.226 +/- 0.069)
      microm to (0.706 +/- 0.082) microm. The same magnitude were also observed after
      body porcelain and enamel porcelain were sintered on with reflectance increased
      from 76.301 +/- 3.097 to 81.529 +/- 4.028, and CIE L* value from 80.694 +/- 1.564
      to 84.604 +/- 2.964. CONCLUSION: The surface roughness of opaque porcelain had
      effects on the reflectance and value of PFM restorations. Within the limitation
      of this study, the recommended Ra range of opaque porcelain was 0.23-0.50 microm.

PMID- 19769259
TI  - [Color property evaluation of 7 kinds of resin-based composite products].
AB  - OBJECTIVE: To investigate the color stability and opacity of seven resin-based
      composite products after ultraviolet irradiation. METHODS: Seven kinds of light
      cured resin-based composite products (Aelite Flo, Filtek Z350 Flowable, Clearfil
      AP-X, Dyract AP, Z100, Durafill VS, Filtek Z350 Universal) were tested in the
      study (five for each group). Changes in color and opacity of test samples were
      determined before and after 8, 16 and 24 h ultraviolet irradiation using the CIE
      1976 L*a*b* system and CIE 1931 XYZ system by a colorimeter. RESULTS: The color
      of resin disks suffering ultraviolet irradiation was different in different
      irradiating time. Color difference values ranged from 1.85-3.21 for 8 h
      ultraviolet irradiation to 2.88-4.55 for 24 h ultraviolet irradiation. Opacity
      values ranged from 0.75-0.82 before ultraviolet irradiation to 0.80-0.98 after 24
      h ultraviolet irradiation. Among all the groups, Z100 and Filtek Z350 Flowable
      showed the biggest color change, while Filtek Z350 Universal showed the highest
      opacity. CONCLUSION: It can be concluded that for some products, ultraviolet
      irradiation leads to color instability and opacity variation.

PMID- 19769260
TI  - [An experimental study on repairing horn-shaped root canal orifice by different
      materials].
AB  - OBJECTIVE: To study the fracture resistance and the failure pattern of horn
      shaped root canal orifice restored by different materials. METHODS: Fifteen human
      maxillary central incisors were selected. After schedule root canal therapy, the
      residual dental roots with horn-shape root canal orifice were prepared. The
      specimens were assigned to three groups randomly. A group was rehabilitated by
      casting metal post-core crown. B group was rehabilitated by prefabricated fiber
      post and composite core crown. C group was rehabilitated by shapeable fiber
      reinforced composite resin post and core crown. Loads were applied on the samples
      at 130 degree to the long axis of the root and measured with universal testing
      machine. The failing patterns were recorded. RESULTS: There were no difference in
      fracture resistance among three groups (P>0.05). But the failing patterns were
      different. A group manifested root fracture and separation between cement and
      root dentin. B group mainly manifested separation between cement and post. C
      group manifested separation between cement and root dentin. CONCLUSION: For
      restoration of residual dental root with horn-shaped orifice, fiber composite
      post-core crown has advantages in residual root protection and once more
      restoration.

PMID- 19769261
TI  - [Positional changes of temporomandibular joint disk and condyle with insertion of
      anterior repositioning splint].
AB  - OBJECTIVE: To measure the positional changes of temporomandibular joint (TMJ)
      disk and condyle with insertion of anterior repositioning splint (ARS) using
      magnetic resonance imaging (MRI) for further understanding of the splint therapy
      mechanisms. METHODS: Twenty-two patients with temporomandibular joint clicks were
      included. 31 TMJs were diagnosed as anterior disk displacement with reduction
      (disk-displaced group), and the other 13 TMJs were normal (normal group). All
      joints were scanned oblique-sagittally by MRI before splint treatment in three
      positions including closed-mouth position of centric occlusion (the position
      before insertion of ARS), incisors' edge to edge position, and mandibular least
      forward protrusion position (the position after insertion of ARS). RESULTS: 1)
      Disk-condyle angle: In closed-mouth position, the average angle was 54.23 degrees
      in the disk-displaced group, while it was 9.80 degrees in the normal group; in
      incisors' edge to edge position and mandibular least forward protrusion position,
      the angle was reduced to normal in most of the disk-displaced cases. 2) Disk
      position: From closed-mouth position to incisors' edge to edge position or
      mandibular least forward protrusion position, the forward displaced disk moved
      backward significantly, while the disk with normal position did not change
      significantly in the three positions. 3) Condyle position: From closed-mouth
      position to incisors' edge to edge position or mandibular least forward
      protrusion position, the condyle moved forward and downward significantly both in
      the disk-displaced group and in the normal group. CONCLUSION: With insertion of
      the splint, the condyle moved anteriorly and inferiorly and the disk moved
      posteriorly, most of the anterior displaced disks could be reduced to normal
      positions in the joint fossa. The result indicated that the splint protruded
      condyle forward and prevented the backward reduced disk from displacing forward
      again during mouth closing.

PMID- 19769262
TI  - [Histomorphological effects of Nd:YAG laser for debonding ceramic brackets on
      rabbit pulp].
AB  - OBJECTIVE: Ceramic brackets debonding by Nd:YAG laser is based on the thermal
      effect of laser, which may cause injury of the pulp tissue. In this study, the
      histological changes of pulp tissue that subjected to Nd: YAG laser irradiation
      with different power and time were observed. METHODS: 20 New Zealand rabbits were
      included in this study. Ceramic brackets were bonded to the 4 incisors as
      routine. The ceramic brackets of left upper teeth that debonded mechanically were
      used as control group, while the brackets of right upper, left lower and right
      lower incisors were debonded by laser with 3 W 3 s (group A), 2 W 5 s (group B)
      and 5 W 2 s (group C) energies, respectively. The teeth were pulled out at 5
      minutes, 1 day, 3 days, 1 week and 1 month after the debonding operations. Slides
      prepared from the pulp tissues of the debonded teeth were used to evaluate the
      injury of laser. RESULTS: In comparison with the control group, pulp tissue of
      teeth that exposed to laser with different energy for 5 minutes showed mild
      capillary dilation. One day later, group A, B and C showed moderate capillary
      dilation, and group C also showed moderate infiltration. At 3 days, inflammation
      was disappeared in group B, whereas capillary dilation was found in group A.
      Hemorrhage and inflammation cells infiltration were found in group C. At 1 week,
      alleviation of capillary dilation was found in group A but not in group C. One
      month later, inflammation disappeared in group A, while pulp tissue in group C
      showed mild edema and capillary dilation. CONCLUSION: Nd:YAG laser of high energy
      may cause injury of the pulp tissue during debonding. Laser energy of 3 W 3 s
      could effectively debond ceramic brackets without irreversible pulp injury.

PMID- 19769263
TI  - [Metameric effect between natural teeth and resin teeth of A2 shade].
AB  - OBJECTIVE: The aim of this study was to determine the metameric color differences
      between natural teeth and three brands of commercially available resin teeth.
      METHODS: The spectral reflectance and color coordinates of natural teeth and
      three brands of commercially available resin teeth of A2 shade were measured with
      a spectrophotometer (PR-650) according to the CIE L*, a*, b* and CIE XYZ color
      scale relative to illuminant D65, A, cool white fluorescent (CWF) and ultraviolet
      (UV), and the metameric indices were calculated to determine the metameric color
      differences between natural teeth and resin teeth. RESULTS: CIE L*, a*, b* values
      were influenced by the type of illuminants in both natural teeth and resin teeth.
      The pattern of spectral reflectance curves for natural teeth and resin teeth of
      A2 shade were different, while there were more than three crossing points among
      each curves, which meant the color of natural teeth and resin teeth of A2 shade
      might be the same under certain illuminant. The metameric indices between natural
      teeth and resin teeth of A2 shade were 3.48, 2.52 and 3.36 under illuminant A;
      1.21, 1.90, and 2.79 under illuminant CWF; 1.59, 2.07, and 4.07 under illuminant
      UV. The metameric indices between resin teeth of different brand were 1.08, 0.10,
      and 1.01 under illuminant A; 1.46, 2.23, and 0.94 under illuminant CWF; and 2.55,
      2.69, and 4.64 under UV. CONCLUSION: Changes in optical properties of resin teeth
      of A2 shade relative to the different illuminants were different from those of
      natural teeth, the metameric effect between natural teeth and resin teeth of A2
      shade were significant. Therefore, shade matching between natural teeth and resin
      teeth should be performed under more than one illuminant.

PMID- 19769264
TI  - [An in vitro study of retentive force and deformation of resin clasp].
AB  - OBJECTIVE: To study the retentive force and deformation of acetal resin clasp.
      METHODS: 40 premolars and 40 molars were cast respectively. Undercut of 0.25 mm
      or 0.50 mm depth were measured for each with undercut gage. According to the type
      of abutment and the depth of undercut, the specimens were divided into 4 groups:
      Premolars with 0.25 mm undercut, premolars with 0.50 mm undercut, molars with
      0.25 mm undercut and molars with 0.50 mm undercut, 20 specimens each group. 10
      three-arm clasps with resin and Co-Cr alloy were fabricated in each group,
      respectively. The clasps were set into the corresponding abutments and soaked in
      distilled water. The retentive force of the clasps when 0, 720, 1440, 2160, 2880,
      3600, 4320 consecutive times of setting in and removing out from the abutments
      were measured. The distance between the tips of retentive arm and resistant arm
      after 0 and 4320 cycles were recorded. RESULTS: 1) The mean retentive force of
      resin clasps (1.69 N) was significantly lower than that of Co-Cr clasps (5.87 N)
      (P<0.01). With the same factors, the retentive force of resin clasps were
      significantly less than that of Co-Cr clasps (P<0.01). The retentive force of
      molar clasps were significantly lower than that of premolar models (P<0.01). The
      retentive force of 0.25 mm undercut clasps were significantly lower than that of
      0.50 mm undercut clasps (P<0.01). With increasing time of the cycles, the
      retentive force of Co-Cr clasps significantly reduced (P<0.01), but the retentive
      force of resin clasps didn't change significantly (P>0.05). 2) After 4320 times,
      the distance between the tips of retentive arm and resistant arm of Co-Cr clasps
      increased significantly (P<0.05), but the distance between the tips of resin
      clasps didn't change significantly (P>0.05). CONCLUSION: The retentive force and
      deformation of the resin clasp are significantly lower than those of Co-Cr clasp.

PMID- 19769265
TI  - [A study on lateral incision after palatoplasty with the levator veli palatini
      retropositioning according to Sommerlad].
AB  - OBJECTIVE: The aim of this study was to explore the relationships between the
      lateral incisions (LI) and cleft extent after palatoplasty with the levator veli
      palatini retropositioning according to Sommerlad, and acquire optimal indication
      without lateral releasing incisions in the surgical treatment of cleft palate.
      METHODS: A total of 176 patients (81 isolated cleft palate, ICP; 74 unilateral
      completely cleft palate, UCCP; 21 bilateral completely cleft palate, BCCP)
      underwent Sommerlad palatoplasty. All dental casts evaluated had been obtained
      after general anaesthesia. Measuring points on the cast were determined as
      follows: Cleft palate width (CPW), interhamular width (IHW), and cleft palate
      index (CPI) defined as the ratio of CPW to IHW. The following analysis was
      carried out: The relationship between CPW and CPI, or between CPW and IHW were
      determined in both ICP, UCCP and BCCP subjects of both sexes together.
      Correlation analysis of the cleft palate width (CPW and CPI) and lateral
      incisions was carried out in ICP, UCCP and BCCP subjects. RESULTS: Among 81
      patients with ICP, 45 patients (55.6%) had no lateral incisions and bilateral
      incisions with length ranged from 5 mm to 30 mm (averaged 12.7 mm +/- 10.0 mm)
      were made in 36 patients (44.4%) after palatoplasty. Among 74 patients with UCCP,
      no lateral incision was made in 5 patients (6.8%), unilateral incisions were made
      in 28 patients (37.8%), and bilateral incisions were made in 41 patients (55.4%).
      Moreover, 21 patients (100%) with BCCP had bilateral incisions after
      palatoplasty. There was a strong correlation between cleft indexes or cleft
      palate width and lateral incisions in isolated cleft palate subjects (r = 0.776,
      P<0.01). Patients with CPI less than 0.31 or CPW less than 12.7 mm were more
      likely to have no lateral incisions following palatoplasty according to
      Sommerlad. CONCLUSION: It is suggested that CPW less than 12.7 mm need no lateral
      incisions for isolated cleft palate repair. Sommerlad palatoplasty with levator
      veli palatini retropositioning leaves few denuded palatal bone is considered to
      be advantageous for maxillary growth.

PMID- 19769266
TI  - [Application of comfort care for dental out-patients].
AB  - OBJECTIVE: To explore and apply the nursing methods of comfort care for dental
      out-patients. METHODS: Control group included 103 dental out-patients who were
      first treated in General Dentistry Department of West China Hospital of
      Stomatology from June to August 2008. Experimental group included 105 dental out
      patients who were first treated in the same hospital from September to November
      2008. Conventional nursing methods were used for control group, and comfort care
      nursing methods were used for experimental group. The patients' degree of
      satisfaction with nursing and oral health knowledge rate after first treatment
      and nursing were investigated. RESULTS: The patients' degree of satisfaction with
      nursing of the control and experimental groups were 72.816% and 98.095%, and the
      patients' oral health knowledge rate of the two groups were 57.282% and 93.333%.
      Both of the investigating results had obvious difference. CONCLUSION: Comfort
      care for dental out-patients can improve patients' degree of satisfaction with
      nursing and increase patients' oral health knowledge rate. Simultaneously,
      comfort care can improve the specialized quality of dental nurses and would
      advantage to build a harmonious relationship between nurses and patients.

PMID- 19769267
TI  - [Survivin small interfering RNA suppresses the growth of adenoid cystic carcinoma
      cell xenografts in vivo].
AB  - OBJECTIVE: To study the effect of stable transfection of small hairpin RNA
      (shRNA) targeting Survivin gene on the growth of adenoid cystic carcinoma (ACC)
      xenografts in nude mice. METHODS: Adenoid cystic carcinoma cell-2 line (ACC-2)
      was transfected with Survivin targeting shRNA eukaryotic expression vector, and
      stable monoclonal cells were selected. Transfected and nontransfected cells were
      respectively inoculated into subcutaneous tissue of nude mice as experimental and
      controls. Survivin mRNA expression of transfected and nontransfected cells were
      detected by reverse transcription-polymerse chain reaction (RT-PCR). Survivin
      protein expression of tumors was investigated by immunohistochemistry. The growth
      of xenograft tumors was observed by measurement of tumor volume. RESULTS:
      Compared to controls, the expression of tumor volume decreased in transfected
      group by pGenesil-shRNA-Survivin. The expression of Survivin mRNA and protein was
      obviously reduced. CONCLUSION: Survivin siRNA markedly suppressed the growth of
      adenoid cystic carcinoma cell xenografts in nude mice through lastingly
      inhibition effect on Survivin.

PMID- 19769268
TI  - [Distribution and genotypic subgroup of oral Saccharomyces albicans isolated from
      cancer patients receiving chemotherapy].
AB  - OBJECTIVE: The objective of this study is to study the distribution and molecular
      characteristics of the oral Saccharomyces albicans (S. albicans) in the cancer
      patients receiving chemotherapy. METHODS: 390 cancer patients receiving
      chemotherapy were sampled by oral mucosal swab. The Candida species were
      identified by CHROMagar Candida differential medium. All the S. albicans were
      genotypic grouped by PCR using primers reported to span a transposable intron
      region in the 25S rDNA gene. RESULTS: The frequency of oral Candida carriage of
      the cancer patients receiving chemotherapy was 53.85% (210/390). Most of them
      were Saccharomyces albicans, the frequency was 48.21% (188/390). The frequency of
      oral Candida glabrata carriage was 5.64% (22/390). Genotypic subgroup A, B, C of
      Saccharomyces albicans were determined, and genotypic group B was the predominant
      group 59.57% (112/188). CONCLUSION: Saccharomyces albicans, especially genotypic
      subgroup B, rather than subgroup A, is the prevalence subpopulation in the oral
      Candida obtained from cancer patients receiving chemotherapy.

PMID- 19769269
TI  - [Effect of Enterococcus faecalis on apoptosis rate and the release of matrix
      metalloproteinase-8 of polymorphonuclear leukocytes].
AB  - OBJECTIVE: To evaluate the release of matrix metalloproteinase-8 (MMP-8) and
      apoptosis rate of polymorphonuclear leukocytes (PMNs) after PMNs was triggered by
      Enterococcus faecalis (E. faecalis) in vitro. METHODS: The activated E. faecalis
      suspension was prepared and added to PMNs suspension as experiment group. As a
      positive control, phorbol myristate acetate (PMA) was used. As negative control,
      PMNs suspension was incubated with PBS. The release of MMP-8 was measured at 0,
      20, 60, 120 min by ELISA method. E. faecalis lysate acted on PMNs as experiment
      group, PMNs suspension was incubated with PBS as negative control, samples in two
      groups were incubated at 37 degrees C for 2, 5, 10, 15 h. The apoptosis rate of
      PMNs was tested by Flow Cytometry. RESULTS: At 0 min, there was no significant
      difference of MMP-8 release in the experiment group and positive control
      (P>0.01); whereas at 60, 120 min, E. faecalis induced a significant lower MMP-8
      release compared with the positive control (P<0.01). The apoptosis rate of PMNs
      in both groups increased along with time, and apoptotic rate in experiment group
      was higher than that in the control group at 2, 5, 10, 15 h (P<0.01). CONCLUSION:
      After E. faecalis act on PMNs, no significant release of MMP-8 from PMNs was
      observed. E. faecalis don't induce PMNs apoptosis delay.

PMID- 19769270
TI  - [Initial study on the discrimination of oral common Actinomycetes with
      metabonomics method].
AB  - OBJECTIVE: The method of metabonomics based on 1H-nuclear magnetic resonance (1H
      NMR) was preliminarily applied to discriminate the oral common Actinomycetes,
      Actinomyces naeslundii ATCC12104 and Actinomyces israelii ATCC12102. METHODS:
      Solutions of Actinomyces naeslundii and Actinomyces israelii with same density
      were made and cultured respectively at BHI liquid culture medium. The
      concentration of bacteria was determined periodically, and then the growth curves
      were drawn. The culture solutions in stationary phase of the two bacteria were
      used to test with the 1H-NMR spectroscopy respectively. The data of 1H-NMR
      spectroscopy results were analyzed by principal components analysis (PCA).
      RESULTS: The PCA showed the obvious clustering phenomena and the points of two
      groups data stayed differentially together by two clusters. Therefore, the NMR
      based metabolomics profiles can discriminate the two different kinds of bacteria.
      CONCLUSION: The analysis technology of metabonomics is expected to be applied to
      rapid identification of actinomycetes.

PMID- 19769271
TI  - [Biocompatibility of new bone tissue engineering scaffolds in vivo].
AB  - OBJECTIVE: To investigate the biocompatibility of new bone tissue engineering
      scaffolds, A:D, L-polylactic acid (PDLLA)/polylactic acid-polyethylene glycol
      polylactic acid-polylactic acid (PLA-PEG-PLA)/Tricalcium phosphate and B:
      PDLLA/PLA-PEG-PLA in vivo, compared with PDLLA in repair of a rabbit mandibular
      body defect. METHODS: 24 New Zealand adult rabbits were divided into 4 groups
      randomly. 15 mm x 6 mm defects were made surgically in the bilateral mandibular
      bodies and each hemi-mandible was assigned as an experimental unit. The defects
      were randomly repaired with scaffold materials in each group. Specimens obtained
      were evaluated with general observation, X-ray, histomorphology and computerized
      graphical analysis at 2, 4 , 8, 12 weeks after surgery. RESULTS: Compared with
      PDLLA, the new scaffold materials B showed biocompatibility. At the same time the
      quantity of new bone produced was much more than that in control group (P<0.05).
      The new scaffold materials A showed the clear chronic granulomatous inflammation.
      CONCLUSION: New scaffold material B had sound biocompatibility. It was much
      better than PDLLA. So it may be an ideal bone tissue engineering scaffold
      material. A is not adapted to be used as scaffold material.

PMID- 19769272
TI  - [A relevant experimental study of alveolar and systemic bone mineral density
      changes in diabetes rats].
AB  - OBJECTIVE: To compare alveolar bone mineral density (BMD) changes of the male and
      female diabetes rats, and male diabetic rats BMD in systemic change. METHODS: 40
      Wistar rats were divided into diabetic group (15 female rats and 15 male rats)
      and control group (5 female rats and 5 male rats). Models of diabetes rats were
      made by peritoneal injection of streptozotocin (STZ). Blood glucose, serum
      insulin, indicators of bone metabolism as well as BMD of mandibular alveolar
      bone, femur and lumbar spine were examined. RESULTS: The BMD of mandibular
      alveolar bone in male rats was higher than the female rats in the two groups
      (P<0.05). The BMD of mandibular alveolar bone of male and female diabetic rats in
      the diabetic group was lower than that in the control group (P<0.05). The BMD of
      male rats in the control group was femur, mandibular alveolar bone, lumbar spine
      from high to low. The BMD of male rats in the diabetic group was mandibular
      alveolar bone, femur, lumbar spine from high to low. CONCLUSION: Osteoporosis
      happen to mandibular alveolar bone of female and male diabetes rats, especially
      in female rats. The BMD of mandibular alveolar bone, femur and lumbar spine in
      the male diabetic rats were lower than that in the control group. Mandibular
      alveolar bone density changes of diabetic rats was in line with the lumbar spine
      and femur's, or mandibular alveolar bone density changes of diabetic rats lags
      behind the lumbar spine and femur's.

PMID- 19769273
TI  - [Construction of nano-granule titanium film and study of its surface topography].
AB  - OBJECTIVE: To construct four different micro- and nano-phase titanium film models
      and investigate the characteristics of their surface micro-topography. METHODS:
      Four different titanium films were prepared on commercial titanium discs, by
      direct current magnetron sputtering, at ambient, 100, 250, 380 degrees C
      substrate temperature, respectively. Their surface topography and crystal sizes
      were investigated using atomic force microscope (AFM) and X-ray diffraction
      (XRD). The size of granule and surface roughness in different group was
      calculated and compared. RESULTS: All samples were covered by a thin film
      consisting of dense round or ovaloid granules. The granules and crystals was
      growing as the substrate temperature increasing. The Ti substrate had greater
      effect on the surface topography of film compared with Si substrate. This kind of
      complex topography caused the surface roughness of Ti substrate group decreased
      as the granules growing. CONCLUSION: In our study, four different micro- and nano
      phase titanium film models were constructed for our coming investigation of their
      topographical influence on biological reaction of proteins and cells. Basic data
      on surface features was obtained for next in vitro and in vivo experiment.

PMID- 19769274
TI  - [Cleidocranial dysplasia: a case report].
AB  - A case of cleidocranial dysplasia (CCD) was reported and relevant literatures
      were reviewed. The diagnosis and treatment of this case were discussed.

PMID- 19769275
TI  - [Immediate implant-support and overdenture retained by conical crowns: three
      cases report].
AB  - Completed denture or immediate completed dentures were manufactured before
      operation to three patients with edentulous mandible and maxillary or severe
      chronic periodontitis. The remnant teeth of patients were extracted. Four Ankylos
      implants were implanted in mandible, and six implants were implanted in
      maxillary. SynCone conical bases were placed into implants, prefabricated conical
      crowns were inserted into conical bases, and temporary dentures were completed.
      After 3-12 months, temporary dentures were replaced by overdenture with casting
      frame. Except that one implant had been lost and was replaced by a new implant
      after 1 month of treatment, the rest implants had no obvious frontal resorption
      in 12-24 months of follow-up.

PMID- 19769276
TI  - [Odontogenic ghost cell carcinoma: a case report].
AB  - Odontogenic ghost cell carcinoma is a rare malignant tumor, which has an
      odontogenic cystic tumor-derived calcification features and characteristics of
      the malignant cytology and invasive growth of the tumor. In the article, a case
      of odontogenic ghost cell carcinoma on maxillary bone was reported.

PMID- 19769277
TI  - [Facial multiple malignant proliferating tricholemmoma: a case report].
AB  - Malignant proliferating tricholemmoma is a very rare dermatic annexal tumor
      originated from outer root sheath cells. In this article, a case of facial
      multiple malignant proliferating tricholemmoma was reported, and its clinical
      pathologic features, differential diagnosis, treatment methods and histogenesis
      were discussed by reviewing relevant literatures.

PMID- 19769278
TI  - [ISKRA guidelines on sore throat: diagnostic and therapeutic approach--Croatian
      national guidelines].
AB  - Sore throat is most commonly caused by viruses, but when caused by bacteria, the
      most important is group A streptococcus (GAS). The aim of these guidelines is to
      determine optimal treatment for streptococcal sore throat and reasonable
      indications for tonsillectomy, as well as recommend how to differentiate
      streptococcal infection for which antibiotics are justified, from numerous other
      sore throats where antibiotics wont have a significant effect on disease course,
      but might contribute to bacterial resistance to antibiotics. The development of
      the guidelines was initiated by the Interdisciplinary Section for Antibiotic
      Resistance Control (ISKRA) of the Croatian Ministry of Health and Social Welfare
      in accordance with the principles of AGREE (Appraisal of Guidelines for Research
      and Evaluation) methodology which means that the guidelines are the result of
      consensus between all interested professional societies and institutions. For
      streptococcal sore throat diagnostics, the Working Group recommends evaluation of
      clinical presentation according to Centor criteria and for patients with Centor
      score 0-1, antibiotic therapy is not recommended nor bacteriological testing,
      while for patients with Centor score 2-4 bacteriological testing is recommended
      (rapid test or culture) as well as antibiotic therapy in case of positive result.
      The drug of choice for the treatment of streptococcal tonsillopharyngitis is oral
      penicillin taken for ten days (penicillin V) or in case of poor patient
      compliance benzathine penicillin G can be administered parenterally in a single
      dose. Other antibiotics (macrolides, clindamycin, cephalosporins, co-amoxiclav)
      are administered only in case of hypersensitivity to penicillin or in recurrent
      infections. Tonsillectomy is a widely accepted surgical procedure that decreases
      the number of sore throats in children and should be performed only if
      indications for this procedure are established. Absolute indications include five
      or more streptococcal infections per year, tonsillitis complications, permanent
      respiratory tract obstruction, obstructive sleep apnea syndrome and suspected
      tonsillar malignancy. Relative indications include chronic tonsillitis and
      occlusion disturbances.

PMID- 19769279
TI  - [Malaria in Croatia in the period between 1987 to 2006].
AB  - A retrospective study about the incidence of malaria in Croatia in the period
      from 1987 to 2006 based on the official data of the Croatian National Institute
      of Public Health. In this period there were 201 cases of malaria registered in
      Croatia. The majority (79.6%) were imported from Africa, a significantly lower
      number from Asia (17%), and several cases from South America or from unknown
      locations. One case ended in death. The causative agents determined are
      Plasmodium falciparum (64.7%), Plasmodium vivax (19.9%), Plasmodium malariae
      (2.0%), Plasmodium ovale (0.5%), and mixed infections (6.0%). The causative agent
      was not discovered in 6.9% of the cases. Chemoprophylaxis was given to patients
      in regular intervals and correctly in 23.3% of the cases, in irregular intervals
      in 8.0% of the cases, incorrectly in 9.5% of the cases, in 9.5% the manner of
      application is unknown, and the remaining 48.7% did not use chemoprophylaxis.
      Approximately 70% of the patients are seamen, and the remaning are workers
      temporarily working in tropical countries and tourists. In conclusion, authors
      argue in favour of prevention measures in persons who stay in malarious areas, by
      providing them with information about the disease, applying permanent prophylaxis
      and rigorous control, as well as monitoring all persons arriving from risky
      areas. On account of the danger of the possible reintroduction of malaria and
      spreading imported causative agents, we should focus our attention primarily on
      the early detection and appropriate therapy of infected cases from abroad.

PMID- 19769280
TI  - [Nonepidermoid carcinomas of the larynx--15 years experience in the single
      institution].
AB  - Nonsquamous carcinomas of the larynx are very rare and present a diverse group of
      diseases. Timely recognition of these tumors is extremely important for their
      different origin, appearance, and approach in the treatment and prognosis.
      Polypoid and submucosal lesions of the larynx are characteristic findings in
      these tumors, and probably the reason for late diagnosis even in the presence of
      symptoms. According to cell origin, nonsquamous carcinomas are classified into
      secretory, connective tissue, lymphoreticular, melanoma, or metastatic carcinoma.
      In this study, 771 laryngeal carcinomas treated during a 15-year (1990-2005)
      period at the Department of Otorhinolaryngology and Head and Neck Surgery,
      University Hospital Center Zagreb, were reviewed to yield 11 cases of nonsquamous
      carcinoma, including one case of neuroendocrine carcinoma, leiomyosarcoma,
      fibrosarcoma, rhabdomyosarcoma, adenoid cystic carcinoma, and plasmacytoma, 2
      cases of chondrosarcoma, and 3 cases of high-grade mucoepidermoid carcinoma. Our
      experience and treatment results for these tumors are presented.

PMID- 19769282
TI  - [Marden-Walker syndrome--a case report].
AB  - Up to now 36 cases of Marden Walker syndrome (MIM # 248700) have been reported.
      The underlying pathological mechanism has not yet been clearly established, but
      it is assumed that it is a developmental disorder of the central nervous system
      which is inherited in an autosomal recessive manner. Three main diagnostic
      criteria are blepharophimosis, congenital joint contractures and mask-like face,
      but numerous other anomalies have been described in these patients. We present a
      girl with clinical characteristics of Marden Walker syndrome, which has not yet
      been reported in our literature. Together with three major and many other
      clinical signs which confirm the diagnosis, our girl also has a vesicoureteral
      reflux and umbilical hernia, which have not yet been described in these patients.

PMID- 19769281
TI  - [Pulmonary Langerhans' cell histiocytosis--case report].
AB  - Authors report a case of a 29-year old patient with pulmonary Langerhans' cell
      histiocytosis who presented with chest pain as a consequence of rib osteolytic
      process. We carried out a diagnostic work-up which included laboratory and
      radiographic analysis, lung function tests, bronchoscopy, cytologic and
      pathologic analysis. After reaching the diagnosis, corticosteroid therapy was
      introduced with long-term follow-up. In this report, we included a brief review
      of pulmonary Langerhans' cell histiocytosis.

PMID- 19769283
TI  - [Electrogastrography in diagnosis of gastric motility disorder in children].
AB  - Gastrointestinal (GI) motility disorders are common in children. Modern
      technology has enabled better understanding, monitoring and treatment of these
      disorders. While gastric anatomic structures are developed prenatally,
      myoelectric activity and motility develop after the birth. Electrogastrography
      (EGG) measures gastric myoelectric activity by electrodes that are positioned on
      the skin. The frequency of gastric waves varies between 0.5-9.0 c/min, usually
      between 2.0-4.0 c/min with amplitudes between 50 and 500 microV. Frequency above
      4.0 c/min is called tachygastria, bellow 2.0 c/min bradygastria, and if the
      dominant frequency cannot be measured it is defined as gastric arrhythmia. EGG is
      useful for monitoring of normal gastric function, determining motoric gastric
      diseases in different states and for the evaluation of treatment of a disease.
      The method is non-invasive, cheap and safe and is easily performed. These
      characteristics make the method useful in pediatrics. The future of the method
      depends mainly on the technical improvement of measurement and data analysis
      which is crucial for better result interpretation.

PMID- 19769284
TI  - [Color Doppler ultrasound of the liver circulation].
AB  - Color Doppler Ultrasound (CDUS) is a valuable method for evaluation of
      morphological and hemodynamic changes of liver circulation occurring in various
      pathological conditions. In some of these conditions CDUS has a decisive
      diagnostic role, thus making further, potentially harmful invasive diagnostic
      procedures unnecessary. Except for the analysis of vascular liver diseases, as
      well as repercussions of circulatory impairment to the liver, utilization of CDUS
      provides valuable information for characterization of diffuse parenchymal and
      focal liver lesions. CDUS has advantages as compared to the other imaging
      modalities as it is widely available and noninvasive. The possible disadvantage
      is not related to the method itself, but is due to lack of expertise, i.e.
      training of the operator. In this article we review the present position of CDUS
      in evaluation of impairment of liver circulation: disorders of the venous outflow
      from the liver (Budd-Chiari syndrome, right-sided heart diseases, veno-occlusive
      disease), disorders of/in liver parenchyma (vascular anomalies-fistulae, solid
      tumors, circulatory changes that occur in diffuse liver diseases) and obstruction
      of the blood inflow to the liver (stenosis and thrombosis of hepatic artery and
      portal vein).

PMID- 19769285
TI  - [Diabetic nephropathy and prevention of diabetic nephropathy caused chronic renal
      insufficiency].
AB  - There is an ongoing trend of a rapid increment in the frequency of diabetes
      mellitus, expecially the non-insulin dependent form. By the end of the 2nd
      millenium 150 million cases were recorded worldwide, while the estimations
      predicted doubling the number by the year 2030. Numerous chronic complications
      accompany the disease, among them micro-, as well as macrovascular prevail,
      affecting small and large blood vessels. This paper provides a literature review
      on the topic of diabetic nephropathy, the main microvascular complication of
      diabetic disease. Microalbuminuria is the earliest sign of the diabetic renal
      involvement, with more than 30 mg and less than 300 mg of albumins in 24 h urine
      sample. The reduction of renal function begins with albuminuria leaving
      microalbuminuria level and entering the pathologic proteinuria range. Renal
      failure advances through the 5 stages, the final fifth occurring fortunately only
      in a minor proportion of the patients. The final stage ensues in 232 of 100 000
      diabetic patients, according to the US data. However, in many developed countries
      there are 30-40% of new patients entering chronic dialysis treatment for diabetic
      nephropathy. Pathogenesis of diabetic nephropathy is based on hyperglycemia and
      distinct hemodynamic changes, glomerular hyperfiltration and high intraglomerular
      pressure. The important role have oxidative stress, advanced glycation end
      products, some cytokines, growth factors and sorbitol pathway. Nevertheless,
      genetic influence is considered by far the most important risk factor for
      diabetic nephropathy. Heritage determines the susceptibility in one and the
      protection in another diabetic patient. At the moment of pathologic proteinuria
      occurrence, glomerular filtration rate begins to decline for 1.2 ml/min/monthly
      in some patients, making the annual reduction of 7-14 ml/min/1.73 m2 of body
      surface area. Improving glycemia, blood pressure control, renal anemia correction
      with rHu-Epo, dyslipidemia control, reduction in protein intake, i.e. management
      of the nongenetic factors, could slower the renal function loss in some of the
      patients. Hence, these measures could reduce the proportion of the patients
      reaching end-stage renal disease, having in mind that morphological and
      functional changes are reversible only within certain limits. Therefore, the
      success of kidney protection is better if commenced earlier.

PMID- 19769286
TI  - [Medical error--Slovenian standpoints and experience].
AB  - Different terms are used for adverse events which occur during the treatment with
      permanent consequences for a patient, in order to avoid calling a procedure not
      in concord with the algorithm a medical error. From the viewpoint of a patient
      suffering lasting consequences or even dying because of malpractice, it is
      totally irrelevant what these procedures are called. Until death occurs, lasting
      consequences may be alleviated through indemnity insurance related to civil
      liability of physicians for malpractice. Prompt admission that medical error has
      occurred, candid discussion with the patient and his family and indemnity payment
      are essential for maintenance of trust in the relation patient-physician. Special
      attention should be paid to informed consent. Only when the details of a
      particular treatment or surgical procedure have been explained to a patient,
      timely and in adequate extent, can the patient freely and independently decide
      upon its acceptance. Physician is the one who should prove that the procedure has
      been properly performed.

PMID- 19769287
TI  - [Medical error--professional liability for malpractice in Bosnia and
      Herzegovina].
AB  - Medical care is frequently compared to aviation, as many of the factors which
      lead to errors in both fields are similar. In this article we review the
      literature on such events and discuss the ethical, legal and practical aspects of
      civil liability in the case of medical error. Ethics, professional policy and the
      law, as well as the relevant empirical literature, suggest that timely and candid
      disclosure should be standard practice. In harmonization to ethical codex, the
      physician is obliged to inform the patient about the origin of medical error.
      Civil liability is one of the most important parts of law that regulates health
      care service. Medical chambers could be having a very important role in
      alternative methods of medical error disciplinary screening proceedings.
      Guidelines for disclosure of medical error to patients, and their families if
      necessary, are proposed.

PMID- 19769288
TI  - [Dr Erwin Treu--the first permanent ophthalmologist in Split].
AB  - Dr. Erwin Treu (Kotor, 1875-Skopje, 1937) was the first permanent ophthalmologist
      in Split, Croatia. He finished his ophthalmological specialization at the Eye
      Clinic in Prague in 1900 at W.P. Czermak. He originates from Tirol. Dr. Treu led
      and organized ophthalmological service in Split and worked from 1902 to 1921 in
      the Split Hospital, and had a private practice until 1923. From 1904 to 1910 he
      temporarily worked outside Split, in Sibenik, Zadar, Dubrovnik, Kotor and
      Cetinje. During the First World War he was a military doctor in Split and Trogir.
      He performed ophthalmological operations, cataracts, glaucomas (iridectomy),
      strabismus (tenotomies), ocular adnexa, injuries, trachoma etc. In 1923 he left
      for Skopje where he at first worked as a medical major in Military Hospital, and
      after that as a primarius in Civil Hospital at the Department of Ophthalmology
      till the end of his life.

PMID- 19769289
TI  - [Thrombophilia--inherited and acquired susceptibility to thrombosis].

PMID- 19769290
TI  - [Molecular evolution of ciliates (Ciliophora) and some related groups of
      protozoans].
AB  - The review summarizes current evidence, including the findings related to
      molecular phylogeny of ciliates (type Ciliophora) and some related groups of
      protozoans. Based on comparison of the sequences of genes encoding various
      ribosomal RNAs (rRNAs), the phylogenetic relationships in seven out of eight
      known classes of ciliates are discussed. The events related to early branching of
      the eukaryotic tree are briefly presented. The evolutionary history of
      amitochondrial protists ids considered with regard to reductionistic evolution
      and archeozoic hypothesis. The phylogenetic relationships among ciliates and
      sister groups of apicomplexans and dinoflagellates are considered.

PMID- 19769291
TI  - [Comparison of Chironomus usenicus and Chironomus curabilis with species of the
      group plumosus (Diptera) inferred from the mitochondrial DNA gene COI and by the
      polytene chromosomes banding pattern].
AB  - The sequence of a 595-bp fragment of the mitochondrial COI gene was determined
      for the species Chironomus usenicus and Chironomus curabilis of the genus
      Chironomus. Phylogenetic reconstructions based on the analysis of the COI gene
      sequence coincide on the whole with cytogenetic data, permitting Ch. usenicus and
      Ch. curabilis to be regarded as members of the group plumosus. Chironomus
      usenicus and Ch. plumosus have identical COI gene sequences. Two hypotheses
      explaining this identity are considered: inheritance of mtDNA from one of the
      parental species during hybridogenesis and horizontal transfer of mitochondrial
      genes.

PMID- 19769292
TI  - [Evolution of gene orders in genomes of cyanobacteria].
AB  - Genomes of 23 strains of cyanobacteria were comparatively analyzed using
      quantitative methods of estimation of gene order similarity. It has been found
      that reconstructions of phylogenesis of cyanobacteria based on the comparison of
      the orders of genes in chromosomes and nucleotide sequences appear to be similar.
      This confirms the applicability of quantitative measures of similarity of gene
      orders for phylogenetic reconstructions. In the evolution of marine unicellular
      plankton cyanobacteria, genome rearrangements are fixed with a low rate (about 3%
      of gene order changes per 1% of 16S rRNA changes), whereas in other groups of
      cyanobacteria the gene order can change several times more rapidly. The gene
      orders in genomes of cyanobacteria and chloroplasts preserve a considerable
      degree of similarity. The closest relatives of chloroplasts among the analyzed
      cyanobacteria are likely to be strains from hot springs belonging to the genus
      Synechococcus. Comparative analysis of gene orders and nucleotide sequences
      strongly suggests that Synechococcus strains from diferent environments (sea,
      fresh waters, hot springs) are not related and belong to evolutionally distant
      lines.

PMID- 19769293
TI  - [Operator-constitutive mutation in the recA gene enhances radiation resistance of
      Escherichia coli].
AB  - Plasmid pUC19-recAoc carrying a mutant allele of the recA gene, which plays the
      key role in the control of the SOS repair system and homologous recombinational
      repair, causes a 1.5-fold increase in radiation resistance of Escherichia coli
      DeltarecA cells, as compared to the wild-type recA+ cells. The protective effect
      of this plasmid is drastically reduced in mutant lexA3 recADelta21 deficient in
      the LexA protein and in induction of the SOS regulon. Plasmid pUC19-recAoc
      effectively suppresses UV sensitivity of the DeltarecA mutant. Mutation recAo20
      allows constitutive high-level synthesis of the RecA protein. This mutation
      impairs the SOS box in the operator site of the recA gene and enhances heterology
      of the dimer LexA binding site. These data confirm that high level of the RecA
      protein synthesis per se is not sufficient for the expression of gamma-inducible
      functions and that the derepression of lexA-dependent genes, other than recA
      gene, is necessary for the complete induction of the SOS repair system.

PMID- 19769294
TI  - [Production of marker-free plants expressing the gene of the hepatitis B virus
      surface antigen].
AB  - The pBM plasmid, carrying the gene of hepatitis B virus surface antigen (HBsAg)
      and free of any selection markers of antibiotic or herbicide resistance, was
      constructed for genetic transformation of plants. A method for screening
      transformed plant seedlings on nonselective media was developed. Enzyme
      immunoassay was used for selecting transgenic plants with HBsAg gene among the
      produced regenerants; this method provides for a high sensitivity detection of
      HBsAg in plant extracts. Tobacco and tomato transgenic lines synthesizing this
      antigen at a level of 0.01-0.05% of the total soluble protein were obtained. The
      achieved level of HBsAg synthesis is sufficient for preclinical trials of the
      produced plants as a new generation safe edible vaccine. The developed method for
      selecting transformants can be used for producing safe plants free of selection
      markers.

PMID- 19769295
TI  - [Use of the gene of antimicrobial peptide cecropin P1 for producing marker-free
      transgenic plants].
AB  - The marker-free transgenic tobacco plants carrying a synthetic gene encoding the
      antimicrobial peptide cecropin P1 (cecP1) under the control of the cauliflower
      mosaic virus 35S RNA promoter were produced. The binary vector pBM, free of any
      selective genes of resistance to antibiotics or herbicides intended for selecting
      transgenic plants, was used for transformation. The transformants were screened
      on a nonselective medium by detecting cecropin P1 in plant cells according to the
      antibacterial activity of plant extracts and enzyme immunoassay. According to the
      two used methods, 2% of the analyzed regenerants were transformants. The
      resulting marker-free plants displayed a considerably increased resistance to
      microbial phytopathogens-the bacterium Erwinia carotovora and fungus Sclerotinia
      sclerotiorum. Thus, the gene cecP1 can be concurrently used as a target gene and
      a screening marker. The utility of cecP1 as a selective gene for direct selection
      of transformed plants is discussed.

PMID- 19769296
TI  - [Genomic instability in sunflower interspecific hybrids].
AB  - The expression of genomic instability was studied at the phenotypical
      (morphological characters, electrophoretic spectra of seed storage proteins) and
      molecular (DNA amplification products) levels in interspecific hybrids (ISHs)
      from crosses of inbred lines of cultivated sunflower Helianthus annuus with
      perennial species of the genus Helianthus and in introgressive lines (ILs)
      produced on their basis. Unstable state of the locus determining the trait of
      lower branching was proved by the method of hybridological analysis. It was shown
      with the use of RAPD markers that the IL genome is characterized by instability
      even after long-term inbreeding (in generations F8-F12). In progenies of
      different combinations of interspecific crosses, identical polymorphous variants
      were revealed for a seed storage protein, helianthinin, and for DNA fragments
      homologous to structural genes of functionally important proteins, suggesting the
      nonrandom character of ISH genome variation. This variation may be determined by
      genome reorganizations under the action of a genome shock induced by
      interspecific hybridization. The factors inducing reorganizations in the genome
      include the activity of mobile genetic elements (MGEs). Using primers specific to
      different MGE families, nucleotide sequences with a high level of homology to the
      sequences of fragments of the mobile elements MuDR, Far1, CACTA, Stowaway, and
      Tourist were identified in the sunflower genome. The possibility of using MGE
      fragments for sunflower genotyping was demonstrated.

PMID- 19769297
TI  - Phenotypic plasticity and between population differentiation in Iris pumila
      transplants between native open and anthropogenic shade habitats.
AB  - Response to environmental heterogeneity caused by human activity was analyzed on
      Iris pumila reciprocal transplants between native steppe and anthropogenic
      (planted pine forest) habitats that were monitored during several growing seasons
      in a protected area of Deliblato Sand. Morphometric traits exhibited significant
      plastic responses to the environmental variability between native and
      anthropogenic habitats that differed in light quantity and quality, as well as in
      some other ecological indices. Significant differentiation between populations
      occupying those habitats was also detected. Plastic responses and population
      differences were substantially related to the variation in general size and had
      the same direction, plastic responses being larger in magnitude. Estimates of
      reproductive and vegetative performance of reciprocal transplants detected home
      site advantage in the native open but not in the secondary shade habitat created
      under anthropogenic influence.

PMID- 19769298
TI  - [Unusual isozyme patterns of glucose-6-phosphate isomerase in polydorids
      (Polychaeta: Spionidae) and the possible mechanisms of their formation].
AB  - The isozyme patterns of glucose-6-phosphate isomerase (GPI) have been analyzed in
      ten species of polychaetes of the genera Polydora and Dipolydora (Polychaeta:
      Spionidae). The GPI patterns of these species have been found to have some
      specific characteristics that cannot be explained in terms of the generally
      accepted views on the nature of isozymes. The patterns are represented by two
      hybridizing isozymes with different expression specificities that exhibit
      coordinated allozymic variation in most individuals of each species studied.
      Involvement of alternative splicing in the expression of the GPI gene is
      considered to be the most probable mechanism of the formation of the unusual GPI
      isozyme patterns in polydorids.

PMID- 19769299
TI  - [The effect of inbreeding on accumulation of complex diseases in genetic
      isolates].
AB  - We have studied the effect of genetic processes in ethnically and demographically
      diverse isolates on the epidemiology of complex diseases. Our long-term studies
      of five indigenous Dagestan ethnic groups have revealed ten genetic isolates with
      aggregation of schizophrenia-related diseases. According to Neel's classification
      (1992), these isolates belong to primary and secondary depending on the duration
      of demographic process. We have found that the average demographic ages of the
      examined primary and secondary isolates were about 4000 and 700 years,
      respectively. The inbreeding level F was studied using two methods: analysis of
      marriage structure in three generations, which is traditional in population
      genetic studies, and analysis of the same structure in extensive pedigrees (up to
      11-13 generations). We have shown that with the second method, the F value
      increases two- to three-fold in various isolates. The accumulated inbreeding in
      the primary isolates proved to be twofold higher than that in the secondary ones.
      Primary isolates have revealed relatively higher genetic and clinical homogeneity
      in combination with higher aggregation of population-specific complex disease
      pathology compared to secondary isolates. A decrease in observed recombinations
      and the number of genomic loci linked with the disease in primary isolates have
      been also demonstrated. Thus, our studies showed that complex diseases can be
      less expensive and mapping of genes for time-consuming if conducted in primary
      rather than in secondary isolates, in particular when dealing with genetically
      heterogeneous outbred human populations.

PMID- 19769300
TI  - Analysis of Y-chromosomal short tandem repeat (STR) polymorphism in an Iranian
      Sadat population.
AB  - The molecular genotyping of individuals and reconstruction of kinship through
      short and highly polymorphic DNA markers, so called short tandem repeats (STR),
      has become one of the important and efficient methods in anthropology studies and
      forensic science. Although many populations have been analyzed, no study has yet
      been carried out on Sadat populations who are putative descendents of Prophet
      Mohammad (peace be upon him). Polymorphisms of 6 Y-STR loci (DYS19, DYS385a/b,
      DYS389II, DYS390, DYS392, and DYS393) have been studied in an unrelated
      population of Sadat males. The aim of this study was to find possible
      similarities within Sadat males, resided in Iran. Among Sadat, DYS385b was proved
      to be the most polymorphic (GD = 0.8588), and DYS392 showed the lowest
      polymorphism (GD = 0.3527). In 50 samples, 45 different haplotypes were found, of
      which 39 haplotypes were unique. In the study, three samples had multi-allelic
      patterns. Haplotype diversity, in regard to these 7 markers was 0.9942.

PMID- 19769301
TI  - [Role of dopamine transporter gene (DAT1) polymorphisms in personality traits
      variation].
AB  - According to psychobiological model of personality proposed by Cloninger,
      personality traits characterizing enhanced tendency to novel stimuli, impulsivity
      and sociability are influenced by dopaminergic system functioning. The present
      study considered both the main effect of two polymorphic loci (VNTR and 2319G>A)
      in dopamine transporter gene (DAT1) and the role of distinct DAT1 gene haplotypes
      in personality traits variation in 592 healthy individuals belonging to different
      ethnicities (men and women). The results of the study revealed the involvement of
      VNTR and 2319G>A polymorphisms in Novelty Seeking variation and the main effect
      of 2319G>A polymorphism on Reward Dependence (TCI) observed in Russian females.
      Moreover, DAT1 gene haplotype effect on Novelty Seeking in Russian females and on
      Persistence (TCI) in Tatar females was demonstrated. Reported in the current
      study results pointed to the involvement of dopaminergic system (DAT1 gene in
      particular) in variation of personality traits characterizing the tendency to
      novel stimuli, purposefulness, and sociability specifically in women.

PMID- 19769302
TI  - [Frequencies of the DRB1, DQA1, DQB1 and TNFA alleles in immigrant population of
      West Siberia].
AB  - Based on population analysis of the DRB1, DQA1, DQB1 and TNFA allele frequency
      distribution patterns, regional features of immunogenetic structure of the
      population of West Siberia were investigated. Statistically significant linkage
      disequilibrium within the HLA class II region, as well as between the TNFA and
      DRB1, DQA1, and DQB1 was demonstrated. Population frequency distribution patterns
      of two- and multilocus haplotypes were examined.

PMID- 19769303
TI  - Patrilocality and recent migrations have little impact on shaping patterns of
      genetic structure of the Armenian population.
AB  - In general, genetic distances between human populations (also within one ethnic
      group) are larger for the Y chromosome markers than for the mtDNA. It is usually
      explained by higher rate of female versus male migration due to the cultural
      practice of patrilocality, when women move to their husbands' residence after
      marriage. Recently found a reversed picture for the genetic variation in some
      ethno-territorial groups confirm the strict role of cultural traditions in
      shaping patterns of populations' genetic structure. To test the role of
      patrilocality for the genetic structure of the Armenian population, we compared
      the Y chromosome and the mtDNA haplotype variations among and between
      geographical groups identified according to paternal (maternal) grandparental
      place of birth, from one side, and the populations currently living in the same
      geographical areas, from the other side. The results demonstrate that the
      Armenian population is regionally more structured for the Y chromosome than for
      the mtDNA. Additionally, in spite of expressed directivity of migration processes
      (caused by the phenomenon of patrilocality as well), the patterns of genetic
      variations for the populations of the same geographic areas remain without any
      significant changes during the last three generations.

PMID- 19769304
TI  - [Comparative characteristics of the gene pool of Teleuts inferred from Y
      chromosomal marker data].
AB  - The gene pool structure of Teleuts was examined and Y-chromosomal haplogroups
      composition and frequencies were determined. In the gene pool of Teleuts, five
      haplogroups, C3xM77, N3a, R1b*, R1b3, and R1a1, were identified. Evaluation of
      the genetic differentiation of the samples examined using analysis of molecular
      variance (AMOVA) with two marker systems (frequencies of haplogroups and Y
      chromosomal microsatellite haplotypes) showed that Bachat Teleuts were equally
      distant from Southern and Northern Altaians. In Siberian populations, the
      frequencies and molecular phylogeny of the YSTR haplotypes within Y-chromosomal
      haplogroup R1a1 were examined. It was demonstrated that Teleuts and Southern
      Altaians had very close and overlapping profiles of R1a1 haplotypes. Population
      cluster analysis of the R1a1 YSTR haplotypes showed that Teleuts and Southern
      Altaians were closer to one another than to all remaining Siberian ethnic groups.
      Phylogenetic analysis of N3a haplotypes suggested specificity of Teleut
      haplotypes and their closeness to those of Tomsk Tatars. Teleuts were
      characterized by extremely high frequency of haplogroup R1b*, distinguished for
      highly specific profile of YSTR haplotypes and high haplotype diversity. The
      results of the comparative analysis suggested that the gene pool of Bachat
      Teleuts was formed on the basis of at least two heterogeneous genetic components,
      probably associated with ancient Turkic and Samoyedic ethnic components.

PMID- 19769305
TI  - [Thermodynamic characterization of di-, tri-, and tetranucleotide loci in
      parthenogenetic lizards Darevskia unisexualis].
AB  - Allelic polymorphism of three microsatellite loci from the genome of
      parthenogenetic lizard Darevskia unisexualis was characterized using analysis of
      free energy (Gibbs energy) of the DNA/DNA duplex formation within the stepwise
      mutational model. It was demonstrated that the number of microsatellite cluster
      monomericic units would change to decrease the mean free energy of the locus. In
      addition, based on the analysis of nucleotide composition, the GC content of each
      locus was evaluated, and belonging of the loci examined to certain isochore
      families was suggested.

PMID- 19769306
TI  - Chromosomal distribution of 18S-25S rDNA in four Lupinus species visualized by
      fluorescence in situ hybridization.
AB  - The number and position of 18S-25S rDNA sites in 4 selected Lupinus species are
      reported for the first time. L. atlanticus, L. subcarnosus and L. paniculatus had
      two rDNA loci, while L. albus exhibited only one loci. Among these 4 species, all
      of them exhibited one large pair of strong signals that extends from the short
      arm to a NOR on a chromosome satellite. L. atlanticus, L. subcarnosus, L.
      paniculatus had one more locus of 18-25S rDNA, but a pair of weak hybridization
      signals were observed in L. paniculatus when 18S-25S rDNA was used as probe. The
      results are discussed in terms of the evolutionary relationships among these
      species.

PMID- 19769307
TI  - [Approaches to the choice of control group for a pathomorphological study of the
      heart].
AB  - It is generally accepted that an optimal control group for pathomorphological
      studies of the heart should be constituted by individuals who died from a
      craniocerebral injury without near-death experience. Polarization microscopy is a
      principal tool for the assessment of pathomorphological characteristics of
      myocardium. The presence of ethanol in the blood of a dead individual is
      associated with enhanced permeability of vascular walls, venous plethora, sludge
      phenomenon, microcirculatory thrombosis, perivascular and intermuscular oedema
      but does not on the whole interfere with the objective evaluation of microscopic
      images of the cardiac muscle.

PMID- 19769308
TI  - [Modern morphological criteria for sudden cardiac death].
AB  - This paper presents results of clinico-morphological analysis of the cases of
      sudden non-violent death from acute heart failure. Histological and
      immunomorphological characteristics of monocytes are discussed as criteria for
      acute myocardial ischemia. Mosaic pattern of myocardial involvement is considered
      to constitute a morphological basis of electrical instability of the heart and,
      accordingly, a cause of sudden cardiac death.

PMID- 19769309
TI  - [Evaluation of health harm severity in psychogenic psychiatric disorders in
      victims of sexual offence].
AB  - The notion of 'psychic trauma" is defined. Medical criteria and characteristic
      clinical manifestations are discussed that may be used for expert estimation of
      the degree of health hazard in the form of psychogenic psychic disorder. It is
      shown that they are applicable to the evaluation of the consequences of a psychic
      trauma as exemplified by the results of forensic psychiatric expert examination
      of sexual offence victims carried out at V.P. Serbsky Research Centre of Social
      and Forensic Psychiatry by clinical and psychopathological methods.

PMID- 19769310
TI  - [Dermatoglyphics in the prognostication of constitutional and physical traits in
      humans].
AB  - The present study was designed to elucidate the relationship between palmar and
      digital dermatoglyphic patterns and descriptive signs of human appearance based
      on the results of comprehensive anthropometric examination of 2620 men and 380
      women. A battery of different methods were used to statistically treat the
      results of dactyloscopic records. They demonstrated correlation between skin
      patterns and external body features that can be used to construct diagnostic
      models for the purpose of personality identification.

PMID- 19769311
TI  - [Peculiarities of wrist bone growth as a criterion for determining the biological
      age of children living under different environmental conditions].
AB  - The paper had the objective to study growth dynamics of short tubular wrist bones
      in children aged from 5 to 16 years and residing in the cities of Shelekhov and
      Irkutsk. The growth rate in the girls from Irkutsk was shown to be fairly uniform
      and proportional; in the boys, it substantially increased at the age of 10-11 and
      15 years. In the boys living in Shelekhov, the bone growth became activated at
      the age of 9 and 15 years. In the girls, it was periodically uniform until the
      age of 9; thereafter, periodicity in the growth of middle and distal phalanxes
      was no longer apparent.

PMID- 19769312
TI  - [Single-stage detection of A and B antigens in the hair by absorption-elution and
      mixed agglutination techniques].
AB  - The proposed method is intended for single-stage detection of A and B antigens in
      ultrafine hair fragments by means of absorption-elution and mixed agglutination
      techniques with the use of a mixture of anti-A and anti-B sera.

PMID- 19769313
TI  - [Detection of blood atropine by gas chromatography with a mass-selective
      detector].
AB  - A method for the detection of atropine in cadaveric blood has been developed
      using a gas chromatograph equipped with a mass-selective detector. The
      concentration range of the method is 20-1000 ng/ml, the limit of sensitivity 10
      ng/ml. Maximum intra-assay error does not exceed 12% and 6% for concentrations of
      20 and 300 ng/ml respectively. The method was validated using material for
      forensic chemical examination.

PMID- 19769314
TI  - [Prognostication of toxicity of a group of chemical compounds comprising anti
      tuberculosis medicines by the quantitative structure-activity correlation
      method].
AB  - Balaban (J), Wiener (W), and Rouvray (R) topological indices as well as detour
      (Ip) and electropy (Ie) indices reflecting the structure of chemical substances
      were used to establish correlation between median lethal dose (LD50) of an anti
      tuberculosis medicine and its molecular structure. Monocyclic compounds showed
      linear correlation between LD50 values and Balaban index (R = 0.93). Correlation
      between a maximum daily dose and electropy index was typical of the products
      having a more complicated structure. Results of this study open up prospects for
      the development of new anti-tuberculosis medicinal preparations characterized by
      reduced toxicity.

PMID- 19769315
TI  - [Detection of nimesulide in biological materials].
AB  - A method for the detection, isolation, and quantitative assay of nimesulide in
      biological materials is described. Therapeutic and toxic levels of this product
      in blood are specified.

PMID- 19769316
TI  - [Sodium intoxication with fatal outcome caused by peritoneal lavage with
      hypertonic solution of NaCl].
AB  - We report a case of fatal sodium poisoning due to the unintentional use of 20%
      hypertonic saline serum during peritoneal lavage after intestinal resection. The
      patient presented with unconsciousness, metabolic acidosis, and plasma sodium
      concentration of 193 mE/l. After 3 hours, he developed paroxysmal
      supraventricular tachycardia, hyperthermia, generalized tonic-clonic convulsions,
      disseminated intravascular coagulation, and adult respiratory distress syndrome.
      The patient died 15 hours after the operation. Pathological examination revealed
      cerebral and lung oedema, pericentral hepatic necrosis, and fibrin thrombi in the
      lungs, stomach, and kidneys. We review, in addition, other reported cases of
      sodium poisoning.

PMID- 19769317
TI  - [On the necessity of standardisation of eugenol-containing preparations].

PMID- 19769318
TI  - [Approaches to optimization of the work of forensic medical specialists (as
      exemplified by the experience gained in the Republic of Tatarstan)].
AB  - Analysis of day-to-day activity of the forensic medical service and results of a
      questionnaire study involving forensic medical examiners, health care providers,
      and law enforcement officers carried out in the Republic of Tatarstan were used
      to develop recommendations for the improvement of the efficiency of work of these
      employee groups. It is concluded that its optimization will require further
      enhancement of material, technical, and methodological support of this service,
      its better organization, financial incentive for the personnel, and mobilization
      of social factors.

PMID- 19769319
TI  - [Forensic-medical aspects of the examination of dermatoglyphic patterns as
      markers of predisposition to drug addiction and related suicides].
AB  - The objective of this study was to compare foot skin patterns from cadavers of 98
      men who died from a drug overdose and 50 male suicide victims (as confirmed
      postmortem inquiries) with those in control samples (from 166 cadavers of men who
      died from other causes). Dermatoglyphic patterns of the sole and toes in the two
      former groups were found to have a number of specific and unidirectional features
      that allowed them to be distinguished from controls. Both drug addicts and self
      murderers showed reduced occurrence of fibular loops and higher frequency of
      whorl patterns on the third toe of the right foot. The frequency of main sole
      line A termini in the two study groups was reduced in field 1' on either foot and
      in field 7 on the right one. The same proved true of line E in field 1" on the
      left foot. An increased ridge count was documented on the first toe of the right
      foot and on the second toe of the left foot.

PMID- 19769320
TI  - [Vladislav Osipovich Merzheevskii].
AB  - This paper describes many-sided activity of V.A. Merzheevsky, one of the founders
      of forensic gynecology in this country. It not only demonstrates an important
      contribution of V.A. Merzheevsky to forensic gynecology but also characterizes
      him as an expert in skopchestvo and an outstanding spa therapist. The paper is
      dedicated to the 130th anniversary of publication of V.A. Merzheevsky's main work
      entitled "Forensic gynecology. The manual for medical and legal professionals"
      (1878).

PMID- 19769321
TI  - Health insurance coverage trends, 1959-2007: estimates from the National Health
      Interview Survey.
AB  - OBJECTIVES: This report presents long-term trends in the number and percentage of
      persons under age 65 years with different types of health insurance coverage and
      with no coverage. It documents changes in how the National Health Interview
      Survey (NHIS) has collected information about coverage over almost 50 years. It
      also compares recent trends in coverage estimates based on the NHIS and the U.S.
      Census Bureau's Current Population Survey (CPS). METHODS: Estimates were derived
      from 32 years of the NHIS, from 1959 to 2007. The types of estimates available
      differ over these years, reflecting changes in the availability of different
      types of coverage and changes in the NHIS questions. Joinpoint regression was
      used to estimate average annual percent change over time and to identify
      statistically significant changes in trends. RESULTS: The percentage of persons
      under age 65 years with private coverage rose between 1959 and 1968, to 79%,
      remained stable until 1980, and then declined to 67% by 2007. During the 1980s,
      the percentage of persons with no coverage increased, while the percentage with
      private coverage declined and the percentage with Medicaid remained stable. Since
      1990, the percentage of nonelderly persons without coverage has remained stable,
      but the number has increased by more than 6 million persons, to 43.3 million in
      2007. During this period, the percentage with private coverage has continued to
      decline, while the percentage with Medicaid has increased. Recent trends in
      coverage based on the NHIS and CPS are similar.

PMID- 19769322
TI  - Benchmarking children's hospitals improves asthma home management.
AB  - Results improve when data are shared openly with hospital quality committee.
      Hospitals share information on what works--and what doesn't. The initiative works
      best when a single individual is given accountability.

PMID- 19769323
TI  - Patient satisfaction upon discharge improved.
AB  - Goal is to improve communications between hospitalists, PCPs. Software includes
      med reconciliation, tests completed at time of discharge. "Personal touch"
      produces better results than communication alone.

PMID- 19769325
TI  - For easy-to-read handouts, take layout into account.

PMID- 19769324
TI  - Multidisciplinary meetings lower LOS, excess days.
AB  - Forty-five days after daily multidisciplinary patient care conferences, LOS
      dropped more than a day. Directors of every department make sure their staff
      attend the meetings, and directors also attend the meetings. The team focuses on
      what is keeping the patient in the hospital and potential barriers to discharge.

PMID- 19769326
TI  - Noncompliance may mean patients misunderstand.

PMID- 19769327
TI  - Joint Commission deadline on MDRO goal is Jan. 1.

PMID- 19769328
TI  - Laboratory studies of molecular growth in the Titan ionosphere.
AB  - Experimental simulations of the initial steps of the ion-molecule reactions
      occurring in the ionosphere of Titan were performed at the synchrotron source
      Elettra in Italy. The measurements consisted of irradiating gas mixtures with a
      monochromatic photon beam, from the methane ionization threshold at 12.6 eV, up
      to and beyond the molecular nitrogen dissociative ionization threshold at 24.3
      eV. Three gas mixtures of increasing complexity were used: N(2)/CH(4)
      (0.96/0.04), N(2)/CH(4)/C(2)H(2) (0.96/0.04/0.001), and
      N(2)/CH(4)/C(2)H(2)/C(2)H(4) (0.96/0.04/0.001/0.001). The resulting ions were
      detected with a high-resolution (1 T) FT-ICR mass spectrometer as a function of
      time and VUV photon energy. In order to interpret the experimental results, a
      Titan ionospheric model was adapted to the laboratory conditions. This model had
      previously allowed the identification of the ions detected in the Titan upper
      atmosphere by the ion neutral mass spectrometer (INMS) onboard the Cassini
      spacecraft. Comparison between observed and modeled ion densities validates the
      kinetic model (reactions, rate constants, product branching ratios) for the
      primary steps of molecular growth. It also reveals differences that we attribute
      to an intense surface chemistry. This result implies that heterogeneous chemistry
      on aerosols might efficiently produce HCN and NH(3) in the Titan upper
      atmosphere.

PMID- 19769329
TI  - Molecular mechanism for lateral lipid diffusion between the outer membrane
      external leaflet and a beta-barrel hydrocarbon ruler.
AB  - Membrane-intrinsic enzymes are embedded in lipids, yet how such enzymes
      interrogate lipid substrates remains a largely unexplored fundamental question.
      The outer membrane phospholipid:lipid A palmitoyltransferase PagP combats host
      immune defenses during infection and selects a palmitate chain using its beta
      barrel interior hydrocarbon ruler. Both a molecular embrasure and crenel in
      Escherichia coli PagP display weakened transmembrane beta-strand hydrogen bonding
      to provide potential lateral routes for diffusion of the palmitoyl group between
      the hydrocarbon ruler and outer membrane external leaflet. Prolines in strands A
      and B lie beneath the dynamic L1 surface loop flanking the embrasure, whereas the
      crenel is flanked by prolines in strands F and G. Reversibly barricading the
      embrasure prevents lipid A palmitoylation without affecting the slower
      phospholipase reaction. Lys42Ala PagP is also a dedicated phospholipase,
      implicating this disordered L1 loop residue in lipid A recognition. The embrasure
      barricade additionally prevents palmitoylation of nonspecific fatty alcohols, but
      not miscible alcohols. Irreversibly barricading the crenel inhibits both lipid A
      palmitoylation and phospholipase reactions without compromising PagP structure.
      These findings indicate lateral palmitoyl group diffusion within the PagP
      hydrocarbon ruler is likely gated during phospholipid entry via the crenel and
      during lipid A egress via the embrasure.

PMID- 19769331
TI  - Mimics of the self-assembling chlorosomal bacteriochlorophylls: regio- and
      stereoselective synthesis and stereoanalysis of acyl(1-hydroxyalkyl)porphyrins.
AB  - Diacylation of copper 10,20-bis(3,5-di-tert-butylphenylporphyrin) using Friedel
      Crafts conditions at short reaction times, high concentrations of catalyst, and 0
      4 degrees C affords only the 3,17-diacyl-substituted porphyrins, out of the 12
      possible regioisomers. At longer reaction times and higher temperatures, the 3,13
      diacyl compounds are also formed, and the two isomers can be conveniently
      separated by normal chromatographic techniques. Monoreduction of these diketones
      affords in good yields the corresponding acyl(1-hydroxyalkyl)porphyrins, which
      after zinc metalation are mimics of the natural chlorosomal bacteriochlorophyll
      (BChl) d. Racemate resolution by HPLC on a variety of chiral columns was achieved
      and further optimized, thus permitting easy access to enantiopure porphyrins.
      Enantioselective reductions proved to be less effective in this respect, giving
      moderate yields and only 79% ee in the best case. The absolute configuration of
      the 3(1)-stereocenter was assigned by independent chemical and spectroscopic
      methods. Self-assembly of a variety of these zinc BChl d mimics proves that a
      collinear arrangement of the hydroxyalkyl substituent with the zinc atom and the
      carbonyl substituent is not a stringent requirement, since both the 3,13 and the
      3,17 regioisomers self-assemble readily as the racemates. Interestingly, the
      separated enantiomers self-assemble less readily, as judged by absorption,
      fluorescence, and transmission electron microscopy studies. Circular dichroism
      spectra of the self-assemblies show intense Cotton effects, which are mirror
      images for the two 3(1)-enantiomers, proving that the supramolecular chirality is
      dependent on the configuration at the 3(1)-stereocenter. Upon disruption of these
      self-assemblies with methanol, which competes with zinc ligation, only very weak
      monomeric Cotton effects are present. The favored heterochiral self-assembly
      process may also be encountered for the natural BChls. This touches upon the long
      standing problem of why both 3(1)-epimers are encountered in BChls in ratios that
      vary with the illumination and culturing conditions.

PMID- 19769332
TI  - Inhibitors of human immunodeficiency virus type 1 (HIV-1) attachment. 5. An
      evolution from indole to azaindoles leading to the discovery of 1-(4
      benzoylpiperazin-1-yl)-2-(4,7-dimethoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)ethane-1,2
      dione (BMS-488043), a drug candidate that demonstrates antiviral activity in HIV
      1-infected subjects.
AB  - Azaindole derivatives derived from the screening lead 1-(4-benzoylpiperazin-1-yl)
      2-(1H-indol-3-yl)ethane-1,2-dione (1) were prepared and characterized to assess
      their potential as inhibitors of HIV-1 attachment. Systematic replacement of each
      of the unfused carbon atoms in the phenyl ring of the indole moiety by a nitrogen
      atom provided four different azaindole derivatives that displayed a clear SAR for
      antiviral activity and all of which displayed marked improvements in
      pharmaceutical properties. Optimization of these azaindole leads resulted in the
      identification of two compounds that were advanced to clinical studies: (R)-1-(4
      benzoyl-2-methylpiperazin-1-yl)-2-(4-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)ethane
      1,2-dione (BMS-377806, 3) and 1-(4-benzoylpiperazin-1-yl)-2-(4,7-dimethoxy-1H
      pyrrolo[2,3-c]pyridin-3-yl)ethane-1,2-dione (BMS-488043, 4). In a preliminary
      clinical study, 4 administered as monotherapy for 8 days, reduced viremia in HIV
      1-infected subjects, providing proof of concept for this mechanistic class.

PMID- 19769333
TI  - Crystalline indole at high pressure: chemical stability, electronic, and
      vibrational properties.
AB  - Vibrational and electronic spectra of crystalline indole were measured up to 25.5
      GPa at room temperature in a diamond anvil cell. In particular, Fourier transform
      infrared (FTIR) spectra in the mid-infrared region and two-photon excitation
      profiles and fluorescence spectra in the region of the HOMO-LUMO transitions were
      obtained. The analysis of the FTIR spectra revealed a large red-shift of the N-H
      stretching mode with increasing pressure, indicating the strengthening of the H
      bond between the NH group and the pi electron density of nearest neighbor
      molecules. The frequencies of four vibronic bands belonging to the (1)L(a) and
      (1)L(b) systems were obtained as a function of pressure. Comparison with
      literature data shows that the crystal acts as a highly polar environment with
      regard to the position of the (1)L(b) origin and of the fluorescence maximum,
      which are largely red-shifted with respect to the gas phase or to solutions in
      apolar solvents. A large, and increasing with pressure, frequency difference
      between the (1)L(b) origin and the blue edge of the fluorescence spectrum
      suggests that the emitting state is (1)L(a), that is known to be more stabilized
      than (1)L(b) by dipolar relaxation. Crystalline indole was found to be very
      stable with respect to pressure-induced reactivity. Only traces of a reaction
      product, containing saturated C-H bonds, are detected after a full compression
      decompression cycle. In addition, differently from many unsaturated compounds at
      high pressure, irradiation with light matching a two-photon absorption for a HOMO
      LUMO transition has no enhancing effect on reactivity. The chemical stability of
      indole at high pressure is ascribed to the crystal structure, where nearest
      neighbor molecules, formig H-bonds, are not in a favorable position to react,
      while reaction between equivalent molecules, for which a superposition of the pi
      electron clouds would be possible, is hindered by H-bonded molecules.
      Consistently, no excimer emission was observed except at the cell opening at the
      end of the compression-decompression run. Extremely limited chemical reactivity
      and excimer formation likely occur at crystal defects, evidencing the strict
      connection between the two phenomena.

PMID- 19769330
TI  - Hydrocarbon hydroxylation by cytochrome P450 enzymes.

PMID- 19769334
TI  - Three-component synthesis of alpha-branched amines under Barbier-like conditions.
AB  - An array of alpha-branched amines has been prepared by using an expedient three
      component Mannich-type reaction among organic halides, aldehyde derivatives, and
      amines. The experimental procedure, which is characterized by its simplicity,
      employs zinc dust for the in situ generation of organozinc reagents. We show that
      this Barbier-like protocol constitutes a useful entry to diarylmethylamines, 1,2
      diarylethylamines, alpha- or beta-amino esters, benzylamines, and beta
      arylethylamines.

PMID- 19769335
TI  - Synthesis of the monomeric counterpart of marinomycin A.
AB  - An efficient and highly convergent synthesis of the monomeric counterpart of the
      antitumor-antibiotic marine natural product marinomycin A was achieved by using
      optically active titanium complexes to control the configuration of the
      stereogenic centers, a highly stereo- and regioselective cross-metathesis to
      generate the (E)-configured C20-C21 double bond, and a Horner-Wadsworth-Emmons
      olefination followed by a Pd-catalyzed Stille cross-coupling to construct the
      tetraene moiety.

PMID- 19769336
TI  - Crystal structures and characterizations of mixed valence 12 L-perovskites
      Ba(4)EuM(3)O(12) (M = Ru and Ir).
AB  - The crystal structures and characterizations of Ba(4)EuM(3)O(12) (M = Ru and Ir)
      are reported. They crystallize in a monoclinic 12-l-perovskite-type structure
      with space group C2/m. The M(3)O(12) trimers and EuO(6) octahedra are alternately
      linked by corner-sharing and form the perovskite-type structure with 12 layers.
      The (151)Eu Mossbauer and X-ray photoelectron spectra reveal that the Eu and M
      ions are in the trivalent and mixed valence (+4.33) oxidation states,
      respectively. Their electrical conductivities show semiconducting behavior with
      an activation energy of approximately 0.2 eV above room temperature and
      demonstrate two-dimensional Mott variable range hopping behavior at low
      temperatures. The magnetic susceptibility and specific heat measurements indicate
      that an antiferromagnetic ordering occurs at 4 K, which is due to the magnetic
      interaction between Ru(3)O(12) trimers. On the other hand, the Ir(3)O(12) trimer
      is found to be nonmagnetic.

PMID- 19769337
TI  - Investigation of potential distribution and the influence of ion complexation on
      diffusion potentials at aqueous-aqueous boundaries within a dual-stream
      microfluidic structure.
AB  - The occurrence of reactions at boundaries between adjacent miscible but unmixed
      aqueous streams coflowing in a microfluidic channel structure has been studied by
      simulation of the diffusion potentials that develop between the two coflowing
      aqueous electrolyte streams and by measurement of the effects of aqueous ion
      complexation on diffusion potentials. The microfluidic structure consisted of a Y
      shaped microchannel with off-chip electrodes immersed in electrolyte reservoirs
      connected by capillaries to the Y-microchannel. The time-dependent, one
      dimensional Nernst-Planck equation employing the electroneutrality condition was
      solved numerically to calculate the diffusion potentials established at the
      boundary between the two coflowing aqueous streams. Under the experimental
      conditions (channel length and width, flow rate) employed, it was shown that the
      use of the Henderson equation was appropriate. It was also shown that the cross
      channel diffusion potential remained constant from the entrance of the channel to
      the exit. The influence of cation complexation by a neutral ionophore was
      investigated by experimentally measured diffusion potentials. It was found that
      potassium complexation by the cyclic polyether 18-crown-6 altered the
      experimental diffusion potential, whereas the interaction of sodium or lithium
      cations with the ionophore did not perturb the diffusion potential. The results
      are consistent with the literature data for aqueous-phase complexation of these
      cations by this ionophore. The results of these investigations demonstrate that
      relatively simple diffusion potential measurements between coflowing streams in
      microchannels may be used as a basis for study of ion complexation reactions
      occurring at boundaries between miscible fluids.

PMID- 19769338
TI  - Directional light emission from propagating surface plasmons of silver nanowires.
AB  - Thin metallic nanowires are highly promising candidates for plasmonic waveguides
      in photonic and electronic devices. We have observed that light from the end of a
      silver nanowire, following excitation of plasmons at the other end of the wire,
      is emitted in a cone of angles peaking at nominally 45-60 degrees from the
      nanowire axis, with virtually no light emitted along the direction of the
      nanowire. This surprising characteristic can be explained in a simple picture
      invoking Fabry-Perot resonances of the forward- and back-propagating plasmons on
      the nanowire. This strongly angular-dependent emission is a critical property
      that must be considered when designing coupled nanowire-based photonic devices
      and systems.

PMID- 19769339
TI  - Synthesis of multifunctional composite microgels via in situ Ni growth on pNIPAM
      coated Au nanoparticles.
AB  - Novel colloidal composites have been designed to incorporate multiple
      functionalities that allow optical detection, magnetic manipulation, molecular
      trapping, and thermal response. Such particles are made of gold nanoparticle
      cores covered by a thin layer of metallic nickel and a poly(N
      isopropylacrylamide) (pNIPAM) shell. While the gold cores provide efficient
      optical response through localized surface plasmon resonances, nickel allows
      external magnetic manipulation and the pNIPAM shell can be swollen or collapsed
      as a function of temperature, thus allowing capture and release of various types
      of molecules.

PMID- 19769340
TI  - Electrochemical atomic force microscopy using a tip-attached redox mediator for
      topographic and functional imaging of nanosystems.
AB  - We describe the development of a new type of high-resolution atomic force
      electrochemical microscopy (AFM-SECM), labeled Tarm (for tip-attached redox
      mediator)/AFM-SECM, where the redox mediator, a ferrocene (Fc), is tethered to
      the AFM-SECM probe via nanometer long, flexible polyethylene glycol (PEG) chains.
      It is demonstrated that the tip-attached ferrocene-labeled PEG chains effectively
      shuttle electrons between the tip and substrate, thus acting as molecular sensors
      probing the local electrochemical reactivity of a planar substrate. Moreover the
      Fc-PEGylated AFM-SECM probes can be used for tapping mode imaging, allowing
      simultaneous recording of electrochemical feedback current and of topography,
      with a vertical and a lateral resolution in the nanometer range. By imaging the
      naturally nanostructured surface of HOPG, we demonstrate that Tarm/AFM-SECM
      microscopy can be used to probe the reactivity of nanometer-sized active sites on
      surfaces. This new type of SECM microscopy, being, by design, free of the
      diffusional constraints of classical SECM, is expected to, in principle, enable
      functional imaging of redox nanosystems such as individual redox enzyme
      molecules.

PMID- 19769341
TI  - Sesquiterpenoids and benzofuranoids from the marine-derived fungus Aspergillus
      ustus 094102.
AB  - Eight drimane sesquiterpenes (1-8), six isochromane derivatives (9-14), and three
      known compounds, daldinin B (15), 9alpha-hydroxy-6beta-[(2E,4E,6E)-octa-2,4,6
      trienoyloxy]-5alpha-drim-7-en-11,12-olide (16), and pergillin (17), were isolated
      from the EtOAc extract of the marine-derived fungus Aspergillus ustus 094102. The
      structures of the new compounds were elucidated on the basis of spectroscopic
      analysis. The cytotoxic effects on A549 and HL-60 cell lines were evaluated by
      SRB and MTT methods. Ustusorane E (13) showed significant cytotoxicity against HL
      60 cells with an IC50 value of 0.13 microM. Ustusolates C (6) and E (8) exhibited
      moderate cytotoxicity against A549 and HL-60 cells with IC50 values of 10.5 and
      9.0 microM, respectively, and ustusolate A (4) showed weak cytotoxicity against
      HL-60 and A549 cells with IC50 values of 20.6 and 30.0 microM, respectively.

PMID- 19769342
TI  - Structural organization of iron oxide nanoparticles synthesized inside hybrid
      polymer gels derived from alginate studied with small-angle X-ray scattering.
AB  - The structural organization of iron oxide nanoparticles (NPs) obtained through in
      situ coprecipitation of iron salts in semi-interpenetrating polymer networks
      (semi-IPNs) constituted of alginate (Alg) and poly(N-isopropylacrylamide)
      (PNiPAAm) has been investigated by means of small-angle X-ray scattering and
      transmission electron microscopy. The oxidation reaction was repeated up to two
      times to increase the amount of iron oxide NPs formed. The results were compared
      to the synthesis of iron oxide nanoparticles in an alginate solution. It has been
      demonstrated that the polymeric gel acts as a spatial framework for iron oxide
      nanoparticles that controls their particle size distribution and that the
      application of repeating oxidation cycles does not increase the polydispersity of
      the iron oxide nanoparticles.

PMID- 19769343
TI  - Water-soluble graphene covalently functionalized by biocompatible poly-L-lysine.
AB  - Graphene sheets functionalized covalently with biocompatible poly-l-lysine (PLL)
      were first synthesized in an alkaline solution. PLL-functionalized graphene is
      water-soluble and biocompatible, which makes it a novel material promising for
      biological applications. Graphene sheets played an important role as connectors
      to assemble these active amino groups of poly-l-lysine, which provided a very
      biocompatible environment for further functionalization, such as attaching
      bioactive molecules. As an example, an amplified biosensor toward H(2)O(2) based
      on linking peroxidase onto PLL-functionalized graphene was investigated.

PMID- 19769344
TI  - Monoalkyl poly(2-methyl-2-oxazoline) micelles. a small-angle neutron scattering
      study.
AB  - This paper presents a SANS study of hydrophobically end-modified poly(2-methyl-2
      oxazoline) (POXZ-C(n)) micelles in aqueous solutions. Strong long-range repulsive
      interactions between the micelles are evidenced by correlation peaks present at
      concentrations as low as 0.5 wt %. Due to the dissymmetry in size between the
      hydrophobic and hydrophilic parts of the chains, the micelles have been analyzed
      using a model of star-like micelles. Large extension of the POXZ arms into the
      micelles can explain the original SANS behavior. The dissociation of the micellar
      structures by adding a complexing agent of the alkyl groups, hydroxypropy-beta
      cyclodextrin (HPbeta-CD), has been followed by SANS. The micelles are
      progressively disrupted by the addition of increasing amounts of HPbeta-CD, and
      the SANS behavior of free chains is recovered in the presence of an excess of the
      complexing agent.

PMID- 19769345
TI  - Correlations between survival probabilities and ionization energies of slow ions
      colliding with room-temperature and heated surfaces of carbon, tungsten, and
      beryllium.
AB  - Survival probabilities, S(a) (%), of hydrocarbon ions C1, C2, and C3 and several
      nonhydrocarbon ions (Ar(+), N(2)(+), CO(2)(+)) on room-temperature (hydrocarbon
      covered) and heated (600 degrees C) surfaces of carbon (HOPG), tungsten, and
      beryllium were experimentally determined using the ion-surface scattering method
      for several incident energies from a few electronvolts up to about 50 eV and for
      the incident angle of 30 degrees (with respect to the surface). A simple
      correlation between S(a) and the ionization energy (IE) of the incident ions was
      found in the semilogarithmic plot of S(a) versus IE. The plots of the data at 31
      eV were linear for all studied surfaces and could be fitted by an empirical
      equation log S(a) = a - b(IE). The values of the parameters a and b were
      determined for all investigated room-temperature and heated surfaces and can be
      used to estimate unknown survival probabilities of ions on these surfaces from
      their ionization energies.

PMID- 19769346
TI  - Conformational changes specific for pseudophosphorylation at serine 262
      selectively impair binding of tau to microtubules.
AB  - Aggregation of the microtubule-associated protein tau into neurofibrillary
      tangles is the pathological hallmark of a variety of dementias. For reasons not
      yet known, tau becomes excessively phosphorylated in Alzheimer's brains and as a
      result no longer binds properly to microtubules. Here we studied the impact of
      phosphorylation on the conformational and binding properties of the repeat region
      of tau (K18) that is necessary for microtubule assembly and forms the core of
      paired helical filaments. To mimic phosphorylation, we introduced four mutations
      of serine to glutamate residues at positions 262, 293, 324, and 356. NMR
      spectroscopy demonstrates that pseudophosphorylation at these sites modifies the
      structural properties in repeats 1 and 2, in particular for Gln265-Lys267. Gln265
      Lys267 are in close proximity to Ser262, the phosphorylation site that most
      strongly attenuates binding to microtubules. In contrast, the
      pseudophosphorylation mimic of tau efficiently interacts with the polyanion
      heparin. Thus, phosphorylation of the repeat region of natively unfolded tau
      induces specific conformational changes that have a strong impact on its
      biological function and involvement in disease.

PMID- 19769347
TI  - Tabu search based strategies for conformational search.
AB  - This paper presents an application of the new nonlinear global optimization
      routine gradient only tabu search (GOTS) to conformational search problems. It is
      based on the tabu search strategy which tries to determine the global minimum of
      a function by the steepest descent-modest ascent strategy. The refinement of
      ranking procedure of the original GOTS method and the exploitation of simulated
      annealing elements are described, and the modifications of the GOTS algorithm
      necessary to adopt it to conformation searches are explained. The utility of the
      GOTS for conformational search problems is tested using various examples.

PMID- 19769348
TI  - Solvation dynamics and adsorption on Ag hydrosols of oxazole: a Raman and
      computational study.
AB  - The interactions between oxazole and water or silver nanoparticles in aqueous
      dispersions have been studied with a computational approach based on ab initio
      molecular dynamics simulations, with the Car-Parrinello method, and density
      functional calculations in combination with Raman and surface enhanced Raman
      scattering (SERS) experiments. The solvation dynamics of oxazole in water allowed
      for the characterization of the hydrogen bond between water and solute, which has
      been shown to occur essentially through the nitrogen atom of the heterocyclic
      molecule. To mimic the solvation process or the adsorption on silver and
      interpreting the corresponding Raman and SERS spectra in aqueous solution or in
      Ag hydrosols, density functional calculations have been carried out on model
      systems made up by oxazole bound to water molecules or to positively charged
      silver clusters. Also, the chemisorption on Ag nanoparticles is found to occur by
      means of the nitrogen atom of oxazole interacting with the metal substrate.

PMID- 19769349
TI  - Forces between blank surfaces as measured by the colloidal probe technique and by
      optical tweezers--a comparison.
AB  - The well-established atomic force microscopy (AFM)-based colloidal probe
      technique (CPT) and optical tweezers (OT) are combined to measure the interaction
      forces between blank SiO(2) surfaces in aqueous ionic solutions (CaCl(2)) of
      varying concentration at pH 7. Spherical colloids (SiO(2), diameter approximately
      4.63 +/- 0.05 microm) taken out of the same batch are used by both methods. In
      the case of CPT, a single colloid is glued to a cantilever, and the interaction
      forces with a plain SiO(2) surface are determined in dependence on the
      concentration of the surrounding medium. For the OT studies, two colloids (one
      fixed to a micropipet by capillary action, the other held with the optical trap)
      are approached to each other in nanometer steps, and the resulting forces are
      measured for the same media as in the CPT experiment. Both techniques fit well to
      each other and enable one to cover interaction energies ranging from 10(-5) to 1
      mN/m. The experimental data are well described by the Derjaguin-Landau-Verwey
      Overbeek (DLVO) theory revealing that the effective surface charge density
      changes slightly with concentration.

PMID- 19769350
TI  - Crystallization of malonic and succinic acids on SAMs: toward the general
      mechanism of oriented nucleation on organic monolayers.
AB  - Self-assembled monolayers (SAMs) were shown to induce very specific oriented
      growth of simple organic and inorganic crystals. Here we present a detailed study
      of the mechanism by which SAMs control the oriented nucleation by examining a
      more complex case of crystallization of bifunctional organic molecules. Malonic
      and succinic acids were grown on the SAMs of HS(CH(2))(10)CO(2)H and
      HS(CH(2))(11)CO(2)H supported on gold films. Each SAM induced a very controlled,
      specific orientation of the crystals. The preferred nucleating planes always
      exhibited an alignment of one of the carboxylic acid groups in the molecules of
      the growing crystal with the carboxylic acid groups on the surface of the SAMs.
      These results suggest that the translation of the structural information through
      the interface occurs by stereochemical registry such that the functional groups
      in the SAM play the role of an oriented surrogate layer for the nucleating
      crystal. These findings are very important to the understanding of the underlying
      principles by which various organic surfaces-and most probably also biological
      templates-control the crystallization process.

PMID- 19769351
TI  - Novel synthetic route to peptide-capped gold nanoparticles.
AB  - A novel synthetic route to peptide-capped gold nanoparticles was demonstrated
      herein. Tetrachloroaurate ions were reduced with 2-[4-(2-hydroxyethyl)-1
      piperazinyl]ethanesulfonic acid (HEPES) under extremely mild conditions (pH 7.2,
      ambient temperature) in the presence of cysteine-terminal desired peptides, so
      that peptide-capped spherical nanoparticles were successfully synthesized. Model
      basic peptides containing the Arg-Pro-Thr-Arg sequence, which is an essential
      motif that specifically binds to film surfaces composed of isotactic poly(methyl
      methacrylate), were employed. Particle sizes were approximately 10 nm, and size
      distributions were narrow. Positive zeta potentials of nanoparticles suggested
      the presence of the Arg-Pro-Thr-Arg sequence on the outermost surface.
      Thermogravimetric analysis revealed that peptides were closely packed on the
      gold's surface. Parameters affecting reaction rates such as peptide structures
      and concentrations were investigated. Native peptide functions were conserved on
      nanoparticles by introducing a certain spacer between cysteine and the Arg-Pro
      Thr-Arg sequence, suggesting that designing suitable peptide structures is
      essential to conserve peptide functions.

PMID- 19769352
TI  - Intraparticle transport and release of dextran in silica spheres with cylindrical
      mesopores.
AB  - The transport of oligomeric molecules in silica spheres with cylindrical
      mesopores has been quantified and related to the structural features of the
      spherical particles and the interactions at the solid-liquid interface. An
      emulsion-solvent evaporation method was used to produce silica spheres having
      cylindrical mesopores with an average pore diameter of 6.5 nm. The transport of
      dextran molecules (fluorescently tagged) with molecular weights of 3000 and
      10,000 g/mol was quantified using confocal laser scanning microscopy (CLSM). The
      intraparticle concentration profiles in the dextran-containing spheres were flat
      at all times, suggesting that the release is not isotropic and not limited by
      diffusion. The release of dextran into the solution is characterized by an
      initial burst, followed by long-term sustained release. The release follows a
      logarithmic time dependency, which was rationalized by coupling concentration
      dependent effective diffusion constants with adsorption/desorption.

PMID- 19769353
TI  - Tuning molecular orbitals in molecular electronics and spintronics.
AB  - With the advance of nanotechnology, a variety of molecules, from single atoms to
      large-scale structures such as graphene or carbon nanotubes, have been
      investigated for possible use as molecular devices. Molecular orbitals (MOs) are
      a key ingredient in determining the transport properties of molecules, because
      they contain all the quantum mechanical information of molecular electronic
      structures and offer spatial conduction channels for electron transport.
      Therefore, the delicate modulation of the MOs enables us to tune the performance
      of electron transport through the molecule. Electric and magnetic fields are
      powerful and readily accessible means for that purpose. In this Account, we
      describe the effects of external fields on molecular electronic and spintronic
      devices. Quantum transport through a molecule that connects source and drain
      electrodes depends strongly on the alignment of molecular energy levels with
      respect to the chemical potentials at both electrodes. This dependence results
      from the energy levels being exploited in resonant tunneling processes when the
      molecule is weakly coupled to the electrodes in the molecular junction. Molecular
      energy levels can be shifted by the Stark effect of an external electric field.
      For a molecule with no permanent dipole moment, the polarizability is the primary
      factor determining the energy shift of each MO, according to the second-order
      Stark effect; more polarizable MOs undergo a larger energy shift. Interestingly,
      even a small shift may lead to a completely nontrivial result. For example, we
      show a magnetic on-off switching phenomenon of a molecule controlled by an
      electric field. If a molecule has a nonmagnetic ground state but a highly
      polarizable magnetic excited state with an energy slightly above the ground
      state, the magnetic excited state can have lower energy than the ground state
      under a sufficiently strong electric field. A magnetic field is normally used to
      control spin orientation in a ferromagnetic system. Here we show that the
      magnetic field can also be used to control MOs. A graphene nanoribbon with zig
      zag-shaped edges (ZGNR) has a ferromagnetic spin ordering along the edges, and
      the spin states have unique orbital symmetries. Both spin polarizations and
      orbital symmetries can simultaneously be controlled by means of an external
      magnetic field. The ZGNR spin-valve devices incorporating this effect are
      predicted to show an extreme enhancement (compared with conventional devices) of
      magnetoresistance due to the double spin-filtering process. In such a system,
      spins are filtered not only by spin matching-mismatching between both electrodes
      as in normal spin-valve devices, but also by the orbital symmetry matching
      mismatching. Thus, a new type of magnetoresistance, and with extremely large
      values, so-called super-magnetoresistance (distinct from the conventional
      tunneling or giant magnetoresistance), is available with this method. MOs are at
      the heart of understanding and tuning transport properties in molecular systems.
      Therefore, investigating the effects of external fields on MOs is important not
      only for understanding fundamental quantum phenomena in molecular devices but
      also for practical applications in the development of interactive devices.

PMID- 19769354
TI  - Alkylamino hydrazide derivatives of hyaluronic acid: synthesis, characterization
      in semidilute aqueous solutions, and assembly into thin multilayer films.
AB  - A series of biodegradable alkylamino hydrazide hyaluronic acid (HA) derivatives
      were prepared and used to design new biocompatible films able to release
      hydrophobic drugs in a controlled manner. The first step of this work thus
      consisted in optimizing the synthetic conditions of hydrazide HA derivatives
      bearing pendant hexyl, octyl, decyl, and citronellyl chains with a degree of
      substitution of 0.05 or 0.10. The behavior in aqueous solution of these water
      soluble modified HA samples was then examined in the semidilute regime. The
      decylamino hydrazide derivatives of HA exhibited remarkable associating
      properties, giving rise to transparent gels. These gels were found to be more
      resistant to degradation by hyaluronidase compared to solutions of nonmodified HA
      at the same concentration. The other derivatives of which the lengths of grafted
      alkyl chains range from 6 to 8 carbon atoms lead to more or less viscous
      solutions. Different viscometric features for these derivatives could be observed
      as a function of the molecular weight of HA. As derivatives prepared from a HA
      sample of 600,000 g/mol (HA-600) exhibited a much higher tendency to self
      aggregate than their counterparts prepared from a HA sample of 200,000 g/mol (HA
      200), the latter derivatives were selected for the build up of multilayer films.
      The topography and z-section of (PLL/HA derivatives) films assembled layer-by
      layer were observed by atomic force microscopy (AFM) in liquid and confocal laser
      scanning microscopy (CLSM) using PLL(FITC) as ending layer. Moreover, the ability
      of the films made of the different HA derivatives to incorporate the hydrophobic
      dye nile red (NR) was investigated. Films containing decylamino hydrazide HA
      derivatives were the most efficient for incorporating and retaining nile red,
      which confirms the formation of stable hydrophobic nanodomains in the films.

PMID- 19769355
TI  - Insertions of silylenes into vinyl epoxides: diastereoselective synthesis of
      functionalized, optically active trans-dioxasilacyclooctenes.
AB  - This communication describes a direct route to functionalized nonracemic trans
      dioxasilacyclooctenes that involves stereoselective silylene insertions into
      vinyl epoxides to provide vinyl silaoxetane intermediates. These strained allylic
      silanes then undergo uncatalyzed allylation of aldehydes to afford trans
      dioxasilacyclooctenes. Diastereoselective additions to these alkenes allow
      efficient transfer of planar chirality to chirality at stereogenic carbon atoms.

PMID- 19769356
TI  - Noncovalent metal-metal interactions: the crucial role of london dispersion in a
      bimetallic indenyl system.
AB  - The nature of the "heterodox" metal-metal bond in bimetallic indenyl systems is
      revealed by a new high-level electronic structure analysis procedure based on
      perturbation theory within a localized molecular orbital basis. Surprisingly
      strong metal-metal interactions are found, and their origin in London dispersion
      effects has been uncovered. The importance of intramolecular van der Waals
      interactions, even for quite small organometallic systems, is highlighted.

PMID- 19769357
TI  - Structure-guided development of selective TbcatB inhibitors.
AB  - The trypanosomal cathepsin TbcatB is essential for parasite survival and is an
      attractive therapeutic target. Herein we report the structure-guided development
      of TbcatB inhibitors with specificity relative to rhodesain and human cathepsins
      B and L. Inhibitors were tested for enzymatic activity, trypanocidal activity,
      and general cytotoxicity. These data chemically validate TbcatB as a drug target
      and demonstrate that it is possible to potently and selectively inhibit TbcatB
      relative to trypanosomal and human homologues.

PMID- 19769359
TI  - Predictions of binding for dopamine D2 receptor antagonists by the SIE method.
AB  - The control of tetralindiol derivative antagonists released through the
      inhibition of dopamine D2 receptors has been identified as a potential target for
      the treatment of schizophrenia. We employed molecular dynamics simulation
      techniques to identify the predicted D2 receptor structure. Homology models of
      the protein were developed on the basis of crystal structures of four receptor
      crystals. Compound docking revealed the possible binding mode. In addition, the
      docking analyses results indicate that five residues (Asp72, Val73, Cys76,
      Leu183, and Phe187) were responsible for the selectivity of the tetralindiol
      derivatives. Our molecular dynamics simulations were applied in combination with
      the solvated interaction energies (SIE) technique to predict the compounds'
      docking modes in the binding pocket of the D2 receptor. The simulations revealed
      satisfactory correlations between the calculated and experimental binding
      affinities of all seven tetralindiol derivative antagonists, as indicated by the
      obtained R2 value of 0.815.

PMID- 19769360
TI  - Multilevel organization in hybrid thin films for optoelectronic applications.
AB  - In this work we report two simple approaches to prepare hybrid thin films
      displaying a high concentration of zeolite crystals that could be used as active
      layers in optoelectronic devices. In the first approach, in order to organize
      nanodimensional zeolite crystals of 40 nm diameter in an electroactive
      environment, we chemically modify their external surface and play on the
      hydrophilic/hydrophobic forces. We obtain inorganic nanocrystals that self
      organize in honeycomb electroluminescent polymer structures obtained by breath
      figure formation. The different functionalizations of the zeolite surface result
      in different organizations inside the cavities of the polymeric structure. The
      second approach involving soft-litography techniques allows one to arrange single
      dye-loaded zeolite L crystals of 800 nm of length by mechanical loading into the
      nanocavities of a conjugated polymer. Both techniques result in the formation of
      thin hybrid films displaying three levels of organization: organization of the
      dye molecules inside the zeolite nanochannels, organization of the zeolite
      crystals inside the polymer cavities, and micro- or nanostructuration of the
      polymer.

PMID- 19769361
TI  - Dendrimer porphyrins and phthalocyanines.

PMID- 19769362
TI  - Vinyl acetate synthesis on homogeneous and heterogeneous Pd-based catalysts: a
      theoretical analysis on the reaction mechanisms.
AB  - Vinyl acetate can be synthetized by both homogeneous and heterogeneous processes
      involving Pd atoms as reaction centers. We have determined the reaction
      mechanisms by means of density functional theory applied to molecular models for
      the homogeneous catalyst and to slabs that model the most active heterogeneous
      ensemble to unravel the similarities and differences in the reaction networks
      under these different conditions. We find that although the reaction network is
      similar, the rate determining step is different. Thus, direct extrapolations from
      organometallic chemistry to gas-phase heterogeneous catalysis should be handled
      with care.

PMID- 19769363
TI  - Enhancing the photochemical stability of N,C-chelate boryl compounds: C-C bond
      formation versus C=C bond cis,trans-isomerization.
AB  - N,C-chelate boron compounds such as B(ppy)Mes(2) (ppy = 2-phenylpyridyl, Mes =
      mesityl) have been recently shown to undergo a facile and reversible C-C/C-B bond
      rearrangement upon irradiation with UV-light, quenching the emission of the
      sample and limiting their use in optoelectronic devices. To address this problem,
      four molecules have been synthesized in which the pi-conjugation is extended
      using either vinyl or acetylene linkers. These compounds, (ph-C[triple bond]C
      ppy)BMes(2) (B1A), (ph-CH=CH-ppy)BMes(2) (B1), [p-bis(ppy
      CH=CH)benzene](BMes(2))(2) (B2), and [1,3,5-tris(ppy-CH=CH)benzene](BMes(2))(3)
      (B3) have been fully characterized by NMR and single-crystal X-ray diffraction
      analyses. All four compounds are light yellow and emit blue or blue-green light
      upon UV irradiation. The acetylene compound B1A has been found to exhibit
      photochemical instability the same as that of the parent chromophore
      B(ppy)Mes(2). In contrast, all of the olefin-substituted compounds are
      photochemically stable, instead undergoing cis-trans isomerization exclusively
      upon exposure to UV light. Experimental and TD-DFT computational results
      establish that the presence of the olefinic bond in B1-B3 provides an alternate
      energy dissipation pathway for the B(ppy)Mes(2) chromophore, stabilizing the
      molecule toward photochromic switching via cis-trans isomerization. Furthermore,
      the incorporation of a cis-trans isomerization pathway may prove to be a useful
      strategy for the stabilization of photochemically unstable chromophores in other
      pi-systems as well.

PMID- 19769364
TI  - Supramolecular polymerization.

PMID- 19769365
TI  - Bisdesmosidic saponins from Securidaca longepedunculata roots: evaluation of
      deterrency and toxicity to Coleopteran storage pests.
AB  - Powdered dry root bark of Securidaca longepedunculata was mixed with maize and
      cowpea and effectively reduced the numbers of Sitophilus zeamais and
      Callosobruchus maculatus emerging from these commodities, respectively, more than
      9 months after treatment. This effect was reciprocated in grain treated with a
      methanol extract of the root bark, indicating that compounds were present that
      were oviposition deterrents or directly toxic to the adults or larvae. Two new
      bisdesmosidic saponins, 3-O-beta-D-glucopyranosyl-28-O-(alpha-L-arabinopyranosyl
      (1 --> 3)-beta-D-xylopyranosyl-(1 --> 4)[beta-D-apiofuranosyl-(1 --> 3)]-alpha-L
      rhamnopyranosyl-(1 --> 2)-[4-O-(4-methoxycinnamoyl-beta-D-fucopyranosyl)])
      medicagenic acid (securidacaside A) and 3-O-beta-D-glucopyranosyl-28-O-(alpha-L
      arabinopyranosyl-(1 --> 3)-beta-D-xylopyranosyl-(1 --> 4)[beta-D-apiofuranosyl-(1
      --> 3)]-alpha-L-rhamnopyranosyl-(1 --> 2)-[4-O-(3,4,5-trimethoxy-(E)-cinnamoyl
      beta-D-fucopyranosyl)])-medicagenic acid (securidacaside B), were isolated from
      the methanol extract of the roots of S. longepedunculata and characterized by
      spectroscopic methods. Securidacaside A, which occurred as (E)- and (Z)
      regioisomers, showed deterrency and toxicity toward C. maculatus and S. zeamais
      and could contribute to the biological activity of the methanol extract. The
      potential to optimize the use of this plant for stored product protection using
      water extracts, which would be appropriate technology for target farmers, is
      discussed.

PMID- 19769367
TI  - Stability of lipid constituents in radiation processed fenugreek seeds and
      turmeric: role of phenolic antioxidants.
AB  - Impact of radiation processing on the lipid profile of fenugreek and turmeric was
      investigated. Oleic and linoleic acid were the dominant fatty acids with an
      appreciable amount of linolenic acid in both cases. Gamma-irradiation did not
      bring about any significant changes in the fatty acid profile of these spices
      despite a high content of unsaturation. The ability of aqueous methanolic extract
      of both spices with high phenolic content to prevent lipid peroxidation suggests
      a possible role of phenolic constituents in preventing lipid radiolysis. Among
      the phenolics identified, kaempferol-3-O-alpha-L-rhamnoside, kaempferol 3,7-O
      alpha-L-dirhamnoside, quercetin 3,7-O-alpha-L-dirhamnoside, and 3-O-alpha-L
      rhamnosyl quercetin are reported here to occur in fenugreek for the first time.
      The role of phenolic antioxidants in preventing lipid oxidation in the above
      spices is discussed.

PMID- 19769366
TI  - Biophysical characterization of Chlamydia trachomatis CT584 supports its
      potential role as a type III secretion needle tip protein.
AB  - Chlamydia are obligate intracellular bacterial pathogens that cause a variety of
      diseases. Like many Gram-negative bacteria, they employ type III secretion
      systems (T3SS) for invasion, establishing and maintaining their unique
      intracellular niche, and possibly cellular exit. Computational structure
      prediction indicated that ORF CT584 is homologous to other T3SS needle tip
      proteins. Tip proteins have been shown to be localized to the extracellular end
      of the T3SS needle and play a key role in controlling secretion of effector
      proteins. We have previously demonstrated that T3SS needle tip proteins from
      different bacteria share many biophysical characteristics. To support the
      hypothesis that CT584 is a T3SS needle tip protein, biophysical properties of
      CT584 were explored as a function of pH and temperature, using spectroscopic
      techniques. Far-UV circular dichroism, Fourier transform infrared spectroscopy,
      UV absorbance spectroscopy, ANS extrinsic fluorescence, turbidity, right angle
      static light scattering, and analytical ultracentrifugation were all employed to
      monitor the secondary, tertiary, quaternary, and aggregation behavior of this
      protein. An empirical phase diagram approach is also employed to facilitate such
      comparisons. These analyses demonstrate that CT584 shares many biophysical
      characteristics with other T3SS needle tip proteins. These data support the
      hypothesis that CT584 is a member of the same functional family, although future
      biologic analyses are required.

PMID- 19769368
TI  - Characterization of an antifungal and cryoprotective class I chitinase from table
      grape berries (Vitis vinifera cv. Cardinal).
AB  - Gene expression of a class I chitinase (Vcchit1b) in the skin of table grapes was
      analyzed as a molecular marker for changes induced at low temperature and also to
      study the effect of high CO(2) levels modulating transcript levels at 0 degrees
      C. An active recombinant VcCHIT1b was overexpressed in Escherichia coli, and as
      the protein was produced as insoluble inclusion bodies, it was solubilized and
      refolded. The purified recombinant chitinase showed an optimum pH of 6.0 and a
      temperature of 50 degrees C, retaining activity at 0 and -10 degrees C. Purified
      chitinase exerted in vitro antifungal activity against Botrytis cinerea.
      Furthermore, recombinant chitinase was able to cryoprotect lactate dehydrogenase
      against freeze/thaw inactivation. However, the recombinant VcCHIT1b did not show
      any antifreeze activity when the thermal hysteresis activity was measured using
      differential scanning calorimetry.

PMID- 19769369
TI  - Effect of glyphosate-boron application on seed composition and nitrogen
      metabolism in glyphosate-resistant soybean.
AB  - The objective of this study was to evaluate the effects of foliar application of
      glyphosate (Gly) alone, boron (B) alone, and Gly-B combined on seed composition
      and nitrogen metabolism in glyphosate-resistant soybean (Glycine max (L.) Merr.).
      No Gly and no B application plants were used as control (C). Results showed that
      Gly, Gly-B, or B applications increased protein, oleic acid, and total amino acid
      concentrations in seed. However, oil and linolenic acid concentrations decreased
      under those treatments compared with the nontreated control. Gly-B combined or B
      treatments increased B concentration in leaves and seed, nitrate reductase
      activity (NRA), and nitrogenase activity and resulted in a significant positive
      correlation between B concentration in leaves and NRA (r = 0.54; P < 0.0001) and
      B concentration in leaves and nitrogenase activity (r = 0.35; P = 0.005). The
      results suggest that Gly-B tank mixing may not antagonize B uptake and
      translocation to leaves and seeds, and the inhibitory effect of Gly on nutrient
      uptake and translocation may depend on the ion species and form of the nutrient
      mixed with Gly. These results demonstrate that Gly-B application alters seed
      composition, nitrogen metabolism, and B status in leaves and seed.

PMID- 19769370
TI  - Dissolution mechanism of crystalline cellulose in H3PO4 as assessed by high-field
      NMR spectroscopy and fast field cycling NMR relaxometry.
AB  - Many processes have been proposed to produce glucose as a substrate for bacterial
      fermentation to obtain bioethanol. Among others, cellulose degradation appears as
      the most convenient way to achieve reliable amounts of glucose units. In fact,
      cellulose is the most widespread biopolymer, and it is considered also as a
      renewable resource. Due to extended intra- and interchain hydrogen bonds that
      provide a very efficient packing structure, however, cellulose is also a very
      stable polymer, the degradation of which is not easily achievable. In the past
      decade, researchers enhanced cellulose reactivity by increasing its solubility in
      many solvents, among which concentrated phosphoric acid (H(3)PO(4)) played the
      major role because of its low volatility and nontoxicity. In the present study,
      the solubilization mechanism of crystalline cellulose in H(3)PO(4) has been
      elucidated by using high- and low-field NMR spectroscopy. In particular, high
      field NMR spectra showed formation of direct bonding between phosphoric acid and
      dissolved cellulose. On the other hand, molecular dynamics studies by low-field
      NMR with a fast field cycling (FFC) setup revealed two different H(3)PO(4)
      relaxing components. The first component, described by the fastest longitudinal
      relaxation rate (R(1)), was assigned to the H(3)PO(4) molecules bound to the
      biopolymer. Conversely, the second component, characterized by the slowest R(1),
      was attributed to the bulk solvent. The understanding of cellulose dissolution in
      H(3)PO(4) represents a very important issue because comprehension of chemical
      mechanisms is fundamental for process ameliorations to produce bioenergy from
      biomasses.

PMID- 19769371
TI  - Interactions of sodium halides with sugars in water: a study of viscosity and
      (1)H spin-lattice relaxation time.
AB  - Viscosity B-coefficients for sodium halides (NaX, X- = Cl-, Br-, and I-) in
      aqueous monosaccharides (d-glucose, d-galactose, d-xylose, and d-arabinose) were
      determined from density and viscosity (eta) measurements at 298.15 K. The
      contributions of solvent property (B1) and the electrolyte-solvent interaction
      (B2) to the B-coefficient were also obtained together with molar activation
      energies (Delta(mu)E0(not equal)) of the electrolytes for viscous flow of the
      aqueous saccharide-electrolyte solution. In addition, 1H spin-lattice relaxation
      times (T1) were measured for two glycosides in D2O with and without sodium
      halides. The results show the interactions between X- and the saccharides are in
      the following order: Cl- > Br- > I-. A linear relationship is observed between
      the relaxation rate (1/T1) and electrolyte concentration.

PMID- 19769372
TI  - Molecular depth profiling of sucrose films: a comparative study of C60(n+) ions
      and traditional Cs(+) and O2(+) ions.
AB  - Depth profiling of sucrose thin films was investigated with time-of-flight
      secondary ion mass spectrometry (TOF-SIMS) using 10 keV C(60)(+), 20 keV
      C(60)(2+), and 30 keV C(60)(3+), and 250, 500, and 1000 eV Cs(+) and O(2)(+) as
      sputtering ions. With C(60)(n+) ions, the molecular ion signal initially
      decreases and reaches a steady state that is about 38-51% of its original
      intensity, depending on the energy of the C(60)(n+) ions. In contrast, with Cs(+)
      and O(2)(+) sputtering, molecular ion signals decrease quickly to the noise
      level, even using very low-energy (250 eV) ions. In addition, the measured width
      of the sucrose/Si interface is much narrower using C(60)(+) ions than that using
      Cs(+) or O(2)(+) ions. To understand the mechanisms of sputtering-induced damage
      by these ions, X-ray photoelectron spectroscopy (XPS) and atomic force microscopy
      (AFM) were used to characterize the bottoms of these sputter craters. XPS data
      show very little chemical change in the C(60)(+) sputter crater, while
      considerable amorphous carbon was found in the O(2)(+) and Cs(+) sputter craters,
      indicating extensive decomposition of the sucrose molecules. AFM images show a
      very flat bottom in the C(60)(+) sputter crater, while the bottoms of the Cs(+)
      and O(2)(+) sputter craters are significantly rougher. We used the sputtering
      model developed by Wucher and co-workers to quantitatively analyze our C(60)(1
      3+) data. The results show that low energy C(60)(+) ions generate a relatively
      thin damage layer with a high molecular ion signal, suggesting that low energy
      C(60)(+) may be the optimal choice for molecular depth profiling of sucrose
      films.

PMID- 19769373
TI  - Sample handling and chemical kinetics in an acoustically levitated drop
      microreactor.
AB  - Accurate measurement of enzyme kinetics is an essential part of understanding the
      mechanisms of biochemical reactions. The typical means of studying such systems
      use stirred cuvettes, stopped-flow apparatus, microfluidic systems, or other
      small sample containers. These methods may prove to be problematic if reactants
      or products adsorb to or react with the container's surface. As an alternative
      approach, we have developed an acoustically-levitated drop reactor eventually
      intended to study enzyme-catalyzed reaction kinetics related to free radical and
      oxidative stress chemistry. Microliter-scale droplet generation, reactant
      introduction, maintenance, and fluid removal are all important aspects in
      conducting reactions in a levitated drop. A three capillary bundle system has
      been developed to address these needs. We report kinetic measurements for both
      luminol chemiluminescence and the reaction of pyruvate with nicotinamide adenine
      dinucleotide, catalyzed by lactate dehydrogenase, to demonstrate the feasibility
      of using a levitated drop in conjunction with the developed capillary sample
      handling system as a microreactor.

PMID- 19769375
TI  - Preparation of micro gold devices on poly(dimethylsiloxane) chips with region
      selective electroless plating.
AB  - A novel protocol for fabrication of micro gold devices on poly(dimethylsiloxane)
      (PDMS) substrates was developed on the basis of region-selective electroless
      plating. The layout of a micro gold device was first photochemically patterned
      onto the PDMS surface through a UV induced poly(acrylic acid) (PAA) grafting
      process. The carboxylic moieties on the grafted PAA served as the scaffold for a
      series of wet chemical reactions that led to the immobilization of gold
      nanoparticles in the UV-exposed region, where electroless plating then occurred
      under the catalysis of the nanoparticles. Gold devices fabricated with such a
      protocol could tolerate the Scotch tape test and survive in a repeated bending
      straightening test. They also showed good stability in acidic and alkaline
      solutions, possessed almost the same electrochemical properties as a standard
      gold disk electrode, and allowed thiol-compounds to form a perfect self-assembled
      monolayer on their surfaces. The fabricated micro gold electrode was demonstrated
      to be suitable as the integrated amperometric detection element in a full PDMS
      micro electrophoresis chip.

PMID- 19769374
TI  - Determination of the absolute thickness of ultrathin Al2O3 overlayers on Si (100)
      substrate.
AB  - The thickness of nanometer Al(2)O(3) films was studied by X-ray photoelectron
      spectroscopy (XPS) and transmission electron microscopy (TEM). The thickness was
      determined from mutual calibration of the XPS and TEM measurements. The thickness
      offset of Al(2)O(3) films was proved to be close to zero by in situ XPS analysis.
      The thicknesses of a series of Al(2)O(3)/Si (100) films with different Al(2)O(3)
      thicknesses could be determined by mutual calibration from the thicknesses
      measured by TEM and XPS. The electron attenuation length of the Al 2p electron
      was determined as 2.4334 nm in the Al(2)O(3) matrix.

PMID- 19769377
TI  - Structure and properties of alkali cobalt double oxides A(0.6)CoO(2) (A = Li, Na,
      and K).
AB  - Lamellar A(x)CoO(2) cobalt double oxides with A = Li, Na, and K (x approximately
      0.6) have been synthesized and their chemical (alkali content, oxidation state,
      and structure) and physical (resistivity, thermopower, magnetization, and
      specific heat) properties have been studied. All the three materials exhibit
      strong electron correlation emphasized by their behavior ranging from Fermi
      liquid to spin-polarized system. Our results show that both the dimensionality of
      the interactions and the nature of the alkali play a determining role on the
      properties.

PMID- 19769376
TI  - Digital microfluidic sampler for a portable capillary electropherograph.
AB  - A new sample introduction/analysis approach was developed by combining a digital
      microfluidic (DMF) device with a portable capillary electrophoresis (CE) analyzer
      based on short separation capillary and contactless conductivity detection. The
      DMF sample injection was performed by transporting sample and buffer droplets in
      succession under the CE capillary inlet end allowing the capillary to be immersed
      into the sample/buffer droplet, and CE separation was performed by applying a
      high voltage between the (grounded) buffer droplet and CE outlet reservoir.
      Electrowetting on dielectric (EWOD) phenomenon was used for droplets actuation.
      With the use of the DMF sampler, CE separation of a mixture of vitamins was
      achieved. A droplet evaporation process with simultaneous concentration of sample
      in the droplet was monitored. It was found that the concentration process closely
      followed the theoretically predicted function.

PMID- 19769378
TI  - Electronic structures of [Ru(II)(cyclam)(Et(2)dtc)](+), [Ru(cyclam)(tdt)](+), and
      [Ru(cyclam)(tdt)](2+): an X-ray absorption spectroscopic and computational study
      (tdt = toluene-3,4-dithiolate; Et(2)dtc = N,N-diethyldithiocarbamate(1-)).
AB  - The reaction of [Ru(III)(cyclam)Cl(2)]Cl with 2 equiv of sodium N,N
      diethyldithiocarbamate in methanol afforded [Ru(II)(cyclam)(Et(2)dtc)](BPh(4))
      (1(BPh(4))). The same reaction with only 1 equiv of toluene-3,4-dithiol and a
      base yielded [Ru(cyclam)(tdt)](PF(6)) (2(PF(6))) which was oxidized by 1 equiv of
      ferrocenium hexafluorophosphate generating [Ru(cyclam)(tdt)](PF(6))(2)
      (2(ox)(PF(6))(2)). The crystal structures of 1 and 2 have been determined by X
      ray crystallography at 100 K. The electronic structures of diamagnetic 1(BPh(4)),
      paramagnetic 2(PF(6)) (S = (1)/(2)), and diamagnetic 2(ox)(PF(6))(2) have been
      studied by magnetochemistry, spectroelectrochemistry, electron paramagnetic
      resonance spectroscopy, and (1)H NMR spectroscopy. X-ray absorption spectroscopy
      on Ru K- and L-edges as well as S K-edges has been employed. Finally, the
      molecular and electronic structures of all three species have been calculated by
      using density functional theory (B3LYP). It is shown that 2(ox) comprises an
      electronic structure which is best described by three resonance structures
      {[Ru(II)(cyclam)(tdt(0))](2+) <--> [Ru(III)(cyclam)(tdt(*))](2+) <-->
      [Ru(IV)(cyclam)(tdt(2-))](2+)} with a closed-shell singlet ground state. This is
      in stark contrast to the isoelectronic iron species, namely,
      [Fe(III)(cyclam)(tdt(*))](2+) which is a singlet diradical with a low-spin ferric
      ion coupled intramolecularly antiferromagnetically to a ligand pi radical
      monoanion (tdt(*))(-).

PMID- 19769379
TI  - Unlabeled hairpin DNA probe for electrochemical detection of single-nucleotide
      mismatches based on MutS-DNA interactions.
AB  - The paper described a label-free assay for the detection of single-nucleotide
      mismatches in which an unlabeled hairpin DNA probe and a MutS protein conjugate
      (His6-MutS-linker peptide-streptavidin binding peptide (HMLS)) are exploited for
      the detection of mismatches by electrochemical impedance spectroscopy (EIS). We
      demonstrate this method for eight single-nucleotide mismatches. Upon
      hybridization of the target strand with the hairpin DNA probe, the stem-loop
      structure is opened forming a duplex DNA. In duplexes containing a single
      nucleotide mismatch, the mismatch is present at the solvent exposed side,
      enabling more effective HMLS recognition and binding. The binding event is
      evaluated by EIS and analyzed with the help of Randles' equivalent circuits. The
      differences in the charge transfer resistance DeltaR(CT) before and after protein
      binding to the duplex DNA allows the unequivocal detection of all eight single
      nucleotide mismatches. DeltaR(CT) allows the discrimination of a C-A mismatch
      with the concentration of the target strand as low as 100 pM.

PMID- 19769380
TI  - Aryl-containing chelates and amine debenzylation to afford 1,3-di-2-pyridyl-2
      azaallyl (smif): structures of {kappa-C,N,N(py)(2)-(2-pyridylmethyl)(2)N(CH(2)(4
      (t)Bu-phenyl-2-yl))}FeBr and (smif)CrN(TMS)(2).
AB  - Aryl-bromide ligand precursors have been prepared with the potential to afford
      tetradentate chelates (2-pyridylmethyl)(3-x)N(CH(2)-2-Aryl)(x) (x = 1, 2)
      containing metal-aryl linkages that promise to impart stronger fields about first
      row transition metals. Oxidative addition to Ni(COD)(2) afforded two diamagnetic
      Ni(II) complexes, {kappa-C,N,N(py)-(2-pyridylmethyl)N(CH(2)(4-(t)Bu-phenyl-2
      yl))(CH(2)(4-(t)Bu-phenyl-2-Br))}NiBr (1-Ni) and {(kappa-C,N,N(py)(2)-(2
      pyridylmethyl)(2)N(CH(2)(4-(t)Bu-phenyl-2-yl))}NiBr (2-Ni) in 96% and 67% yield,
      respectively. Extending these synthetic efforts to iron provided {kappa
      C,N,N(py)(2)-(2-pyridylmethyl)(2)N(CH(2)(4-(t)Bu-phenyl-2-yl))}FeBr (2-Fe, X-ray)
      in 91% yield via reduction of an adduct, {kappa-N,N(py)(2)-(2
      pyridylmethyl)(2)N(CH(2)(4-(t)Bu-phenyl-2-Br))}FeBr(2) (3-Fe). 5-Coordinate 2-Fe
      possessed a pseudo-tbp structure, and SQUID magnetometry showed it to be S = 2
      with significant zero field splitting (ZFS). 2-Fe was initially prepared via
      oxidative addition to Fe{N(TMS)(2)}(2)(THF) upon disproportionation to "Fe(0)"
      and 2 Fe{N(TMS)(2)}(3), but when this approach was attempted with
      Cr{N(TMS)(2)}(2)(THF)(2), the azaallyl complex {kappa-N,N(py)(2)-1,3-dipyridyl-2
      azaallyl}CrN(TMS)(2) ((smif)CrN(TMS)(2), 4-Cr, X-ray), formed instead (>50%) via
      amine debenzylation. An alternative route consisting of addition of 1,3-di-2
      pyridyl-2-azapropene to Cr{N(TMS)(2)}(2)(THF)(2) afforded 4-Cr in 74% yield.
      Pseudo-square planar 4-Cr was also S = 2 (SQUID) with marked ZFS. The
      dipyridylazaallyl ligand "smif" imparts a remarkable optical density to 4-Cr via
      intraligand bands at 675 nm (epsilon approximately 15,000 M(-1)cm(-1)) and 396 nm
      (epsilon approximately 27,000 M(-1)cm(-1)). The effective fields of the chelate
      complexes are discussed, and a comparison of smif to isoelectronic NHC ligands is
      given.

PMID- 19769381
TI  - Controlled manipulation of bacteriophages using single-virus force spectroscopy.
AB  - A method is described for the site-directed manipulation of single filamentous
      bacteriophages, by using phage display technology and atomic force microscopy. f1
      filamentous bacteriophages were genetically engineered to display His-tags on
      their pIX tail. Following adsorption on nitrilotriacetate-terminated surfaces,
      force spectroscopy with tips bearing monoclonal anti-pIII antibodies was used to
      pull on individual phages via their pIII head. Analysis of the force-extension
      profiles revealed that upon pulling, the phages are progressively straightened
      into an extended orientation until rupture of the anti-pIII/pIII complex. The
      single-virus manipulation technique presented here provides new opportunities for
      understanding the forces driving cell-virus and material-virus interactions, and
      for characterizing the binding properties of polypeptide sequences or proteins
      selected by the phage display technology.

PMID- 19769382
TI  - Synthesis, structures, spectroscopic and electrochemical properties of dinitrosyl
      iron complexes with bipyridine, terpyridine, and 1,10-phenathroline.
AB  - Three new dinitrosyl iron complexes LFe(NO)(2) (L = 2,2'-bipyridine (bipy) (1),
      2,2',2''-terpyridine (terpy) (2) and 1,10-phenathroline (phen) (3)) were
      synthesized by the reaction of Fe(NO)(2)(CO)(2) with corresponding ligands in
      tetrahydrofuran. Complexes 1-3 were studied using IR, UV-vis, MS, NMR, and
      electrochemical techniques. Complexes 1 and 2 were also characterized using
      single crystal X-ray diffraction analysis. IR spectra of complexes 1-3 display
      two strong characteristic NO stretching frequencies (nu(NO)) in the region
      reflecting donor properties of the ligands. Cyclic voltammetry studies show two
      quasi-reversible one-electron reductions for all complexes. Electrochemical
      investigations using different concentrations show that an irreversible one
      electron reduction at -1.85 V for complex 2 and -1.80 V for complex 3 are from
      solvated species. Single-crystal X-ray structural analysis reveals that complex 1
      crystallizes in the triclinic P1 space group and the asymmetric unit consists of
      one Fe(NO)(2)(bipy) molecule with the two NO groups located on two sides of
      Fe(bipy) plane. Complex 2 crystallizes in monoclinic P21/n space group, and the
      asymmetric unit contains one Fe(NO)(2)(terpy) molecule, in which the NO groups
      are located on two sides of the plane consisted of Fe and two coordinated pyridyl
      rings, but almost parallel to the uncoordinated pyridyl ring. The crystal
      packings of both complexes 1 and 2 show intermolecular H-bonding and strong pi-pi
      stacking interactions.

PMID- 19769384
TI  - Rare sandwich-type polyoxomolybdates constructed from Di-/tetra-nuclear
      transition-metal clusters and trivacant keggin germanomolybdate fragments.
AB  - Two types of rare sandwich-type germanomolybdates [Na(12)(H(2)O)(36)][Cu(2)(beta
      Y-GeMo(9)O(33))(2)].3H(2)O (1), [N(CH(3))(4)](4) [Na(6)(H(2)O)(24)][Cr(2)(beta-Y
      GeMo(9)O(33))(2)].7H(2)O (2), and [Na(11)(H(2)O)(25)]H[M(4)(H(2)O)(2)(alpha-B
      GeMo(9)O(34))(2)].6H(2)O (M = Ni(II) for 3, M = Mn(II) for 4 and M = Co(II) for
      5) have been synthesized and characterized by elemental analyses, ICP spectra, IR
      spectroscopy, UV spectroscopy, thermogravimetry (TG) analyses (for 1-3), X-ray
      photoelectron spectroscopy (XPS) (for 1 and 3), X-ray powder diffraction (XRPD)
      (for 1 and 3) and single-crystal X-ray diffraction. To our knowledge, 1-5
      represent the first sandwich-type germanomolybdates containing both {beta-Y
      GeMo(9)O(33)}/{alpha-B-GeMo(9)O(34)} fragments and transition-metal clusters.
      Interestingly, 1 and 2 display the rare dinuclear transition-metal substituted
      sandwich-type structures with unusual trivacant {beta-Y-GeMo(9)O(33)}
      germanomolybdate units whereas 3-5 exhibit the first tetranuclear transition
      metal substituted sandwich-type structures with familiar trivacant {alpha-B
      GeMo(9)O(34)} germanomolybdate units. Surface photovoltage spectroscopy (SPS) and
      electric field induced surface photovoltage spectroscopy (EFISPS) measurements
      reveal that 1 and 3 bear the behavior of the n-type semiconductor. Magnetic
      measurements indicate 1 and 3 demonstrate antiferromagnetic exchange interactions
      and ferromagnetic exchange interactions, respectively.

PMID- 19769383
TI  - An approach to the site-selective diversification of apoptolidin A with peptide
      based catalysts.
AB  - We report the application of peptide-based catalysts to the site-selective
      modification of apoptolidin A (1), an agent that displays remarkable selectivity
      for inducing apoptosis in E1A-transformed cell lines. Key to the approach was the
      development of an assay suitable for the screening of dozens of catalysts in
      parallel reactions that could be conducted using only microgram quantities of the
      starting material. Employing this assay, catalysts (e.g., 11 and ent-11) were
      identified that afforded unique product distributions, distinct from the product
      mixtures produced when a simple catalyst (N,N-dimethyl-4-aminopyridine (10)) was
      employed. Preparative reactions were then carried out with the preferred
      catalysts so that unique, homogeneous apoptolidin analogues could be isolated and
      characterized. From these studies, three new apoptolidin analogues were obtained
      (12-14), each differing from the other in either the location of acyl group
      substituents or the number of acetate groups appended to the natural product
      scaffold. Biological evaluation of the new apoptolidin analogues was then
      conducted using growth inhibition assays based on the H292 human lung carcinoma
      cell line. The new analogues exhibited activities comparable to apoptolidin A.

PMID- 19769385
TI  - Reduction of an hexamethylphosphoramide degradation product: a diazabutadiene.
AB  - Alkali metal over-reduction of an electron acceptor in the presence of a hydrogen
      atom donor, in hexamethylphosphoramide (HMPA), results in a radical that is not
      simply the anion radical of the acceptor. This new species exhibits an enigmatic
      EPR pattern. Using 15N and 2H labeling studies, the "HMPA degradation product"
      was found to be the anion radical of N,N'-dimethyl-1,4-diazabutadiene. DFT
      calculations support this assignment and a mechanism for its formation.

PMID- 19769386
TI  - Approach to tetrodotoxin via the oxidative amidation of a phenol.
AB  - An approach to tetrodotoxin that relies on the oxidative amidation of methyl 4
      hydroxyphenylacetate as a key step is described. The stereoselective introduction
      of a beta-hydroxynitrile functionality on one of the double bonds of the emerging
      dienone is achieved through an intramolecular nitrile oxide cycloaddition
      fragmentation sequence.

PMID- 19769387
TI  - A versatile preparation of Gelander-type p-terphenyls from a readily available
      diacetylenic precursor.
AB  - A series of doubly bridged p-terphenyls (4) have been synthesized utilizing a
      facile three-step synthesis starting from the readily available diacetylenic
      precursor (1) in excellent overall yields, and their structures were confirmed by
      1H/13C NMR spectroscopy as well as by X-ray crystallography. The racemization
      barrier between the meso and chiral atropisomers of one of the derivatives of 4
      was found to be approximately 12 kcal/mol by variable-temperature NMR
      spectroscopy. The versatility of the protocol developed herein was further
      demonstrated by the preparation of a quadruply bridged penta-p-phenylene
      derivative.

PMID- 19769388
TI  - An unprecedented oxidative Wagner-Meerwein transposition.
AB  - An oxidative Wagner-Meerwein transposition involving different functionalities
      mediated by a hypervalent iodine reagent has been accomplished. The strategy fits
      within the concept of "aromatic ring umpolung" and allows rapid access to highly
      functionalized cores.

PMID- 19769389
TI  - Effect of H/D isotopomerization in the assay of resveratrol by tandem mass
      spectrometry and isotope dilution method.
AB  - Resveratrol is a phytoalexin found in several plant tissues and present in wines,
      which is supplied as a nutritional supplement. Different studies have revealed
      its beneficial effects as anticancer, antiviral, neuroprotective, antiaging, and
      anti-inflammatory natural active principle. The assaying of resveratrol by mass
      spectrometry and isotope dilution method, using a stable [(2)H(4)] analogue, has
      required a full elucidation of its gas-phase H/D isotopomerization. Either
      selected ion monitoring (SIM) or multiple reaction monitoring (MRM) methods have
      been used for the evaluation of the amount of resveratrol present in wine and
      plasma samples in the negative ionization mode. In all instances the acquired
      accuracy, limit of quantitation (LOQ), and limit of detection (LOD) are fit for
      the intended purpose of the assay.

PMID- 19769390
TI  - Ammonia borane hydrogen release in ionic liquids.
AB  - The rate and extent of H(2)-release from ammonia borane (AB), a promising, high
      capacity hydrogen storage material, was found to be enhanced in ionic-liquid
      solutions. For example, AB reactions in 1-butyl-3-methylimidazolium chloride
      (bmimCl) (50:50-wt %) exhibited no induction period and released 1.0 H(2)-equiv
      in 67 min and 2.2 H(2)-equiv in 330 min at 85 degrees C, whereas comparable solid
      state AB reactions at 85 degrees C had a 180 min induction period and required
      360 min to release approximately 0.8 H(2)-equiv, with the release of only another
      approximately 0.1 H(2)-equiv at longer times. Significant rate enhancements for
      the ionic-liquid mixtures were obtained with only moderate increases in
      temperature, with, for example, a 50:50-wt % AB/bmimCl mixture releasing 1.0 H(2)
      equiv in 5 min and 2.2 H(2)-equiv in only 20 min at 110 degrees C. Increasing the
      AB/bmimCl ratio to 80:20 still gave enhanced H(2)-release rates compared to the
      solid-state, and produced a system that achieved 11.4 materials-weight percent
      H(2)-release. Solid-state and solution (11)B NMR studies of AB H(2)-release
      reactions in progress support a mechanistic pathway involving: (1) ionic-liquid
      promoted conversion of AB into its more reactive ionic diammoniate of diborane
      (DADB) form, (2) further intermolecular dehydrocoupling reactions between
      hydridic B-H hydrogens and protonic N-H hydrogens on DADB and/or AB to form
      neutral polyaminoborane polymers, and (3) polyaminoborane dehydrogenation to
      unsaturated cross-linked polyborazylene materials.

PMID- 19769391
TI  - Antibody-drug conjugates: linking cytotoxic payloads to monoclonal antibodies.
AB  - Antibody-drug conjugates (ADCs) combine the specificity of monoclonal antibodies
      (mAbs) with the potency of cytotoxic molecules, thereby taking advantage of the
      best characteristics of both components. Along with the development of the mAbs
      and cytotoxins, the design of chemical linkers to covalently bind these building
      blocks is making rapid progress but remains challenging. Recent advances have
      resulted in linkers having increased stability in the bloodstream while allowing
      efficient payload release within the tumor cell.

PMID- 19769392
TI  - PEGylated nanoceria as radical scavenger with tunable redox chemistry.
AB  - We report the direct synthesis of cerium oxide nanoparticles (CNPs) in
      polyethylene glycol (PEG) based solutions with efficient radical scavenging
      properties. Synthesis of CNPs in PEG demonstrated a concentration dependent (of
      PEG) redox activity characterized by UV-visible spectroscopy. PEGylated CNPs
      acted as efficient radical scavengers, and superoxide dismutase (SOD) activity of
      CNPs synthesized in various concentration of PEG did not reduce compared to bare
      nanoceria. In addition to superoxide, PEGylated nanoceria demonstrated quenching
      of peroxide radicals as well. It was observed that the reaction with hydrogen
      peroxide leads to the formation of a charge transfer complex governed by the
      concentration of PEG. The stability of the charge transfer complex provides the
      tunable oxidation state of CNPs. The stability of this complex influences the
      regenerative capacity of the active 3+ oxidation state of CNPs. The cell
      viability as well as SOD activity of PEGylated CNPs is compared to those of bare
      CNPs, and the differences are outlined.

PMID- 19769393
TI  - HPLC assay of tomato carotenoids: validation of a rapid microextraction
      technique.
AB  - Carotenoids are studied for their role as pigments and as precursors of aromas,
      vitamin A, abscisic acid, and antioxidant compounds in different plant tissues. A
      novel, rapid, and inexpensive analytical protocol is proposed to enable the
      simultaneous analysis of four major tomato carotenoids: lutein, lycopene, beta
      carotene, and phytoene. Microextraction is performed in the presence of sodium
      chloride, n-hexane, dichloromethane, and ethyl acetate on fresh tomato powder
      that has been finely ground in liquid nitrogen. The carotenoids are extracted by
      agitation and centrifugation and then analyzed by HPLC using a diode array
      detector. The principal advantage of this extraction resides in the absence of an
      evaporation step, often necessary to assay tomato carotenoids other than
      lycopene. Whatever the carotenoid, tests for accuracy, reproducibility, and
      linearity were satisfactory and indicative of the method's reliability. The
      stability of extracts over time (several days at -20 degrees C) as the
      satisfactory sensitivity of the assay whatever the fruit ripeness had a part in
      the robustness of the method. Reliable, rapid, simple, and inexpensive, this
      extraction technique is appropriate for the routine analysis of carotenoids in
      small samples.

PMID- 19769394
TI  - Structure of [Pb(Gly-H)]+ and the monosolvated water and methanol solvated
      species by infrared multiple-photon dissociation spectroscopy, energy-resolved
      collision-induced dissociation, and electronic structure calculations.
AB  - Infrared multiple-photon dissociation (IRMPD) spectroscopy, collision-induced
      dissociation mass spectrometry, and theoretical calculations are combined to
      provide new insights into the structure and dissociation of lead(II) complexed
      with the conjugate acid of the amino acid glycine ([Pb(Gly-H)](+)) in the
      presence and absence of solvent. Unexpectedly, these experiments show the main
      site of lead(II) coordination to be the deprotonated amino group of glycine, with
      additional coordination to the carbonyl group. In such a structure lead(II) can
      act as an effective conduit for proton/hydrogen shifts, making H(2)O loss
      competitive with that of CO in the [Pb(Gly-H)](+) complex and leading to solvent
      deprotonation and formation of [PbOR(Gly)](+) (R = H, CH(3)) ions when solvent is
      present in the complex. The structural assignments based on IRMPD spectroscopy
      are complemented with isotopic labeling experiments (H(2)(18)O) and experiments
      done on the ethyl ester of glycine.

PMID- 19769395
TI  - A fluorogenic, nucleic acid directed "click" reaction.
AB  - A fluorogenic, nucleic acid directed, Cu(+)-catalyzed chemical reaction was
      developed that allows sequence-specific detection of nucleic acids at
      concentrations as low as 20 nM through monitoring of the increase of the
      fluorescence intensity. A single nucleotide mismatch in the template strand leads
      to the complete inhibition of this reaction. We observed that a Cu(+) ion
      stabilized with a water-soluble ligand is a significantly more efficient catalyst
      than free Cu(+).

PMID- 19769396
TI  - Sensitive valence structures of [(pap)(2)Ru(Q)](n) (n = +2, +1, 0, -1, -2) with
      two different redox noninnocent ligands, Q = 3,5-Di-tert-butyl-N-aryl-1,2
      benzoquinonemonoimine and pap = 2-phenylazopyridine.
AB  - The complexes [(pap)(2)Ru(Q)]ClO(4), [1]ClO(4)-[4]ClO(4), with two different
      redox noninnocent ligands, Q = 3,5-di-tert-butyl-N-aryl-1,2-benzoquinonemonoimine
      (-aryl = m-(Cl)(2)C(6)H(3) (1(+)), C(6)H(5) (2(+)), m-(OCH(3))(2)C(6)H(3) (3(+)),
      and m-((t)Bu)(2)C(6)H(3) (4(+))) and pap = 2-phenylazopyridine, have been
      synthesized and characterized using various analytical techniques. The single
      crystal X-ray structure of the representative [2]ClO(4).C(7)H(8) exhibits
      multiple intermolecular C-H...O hydrogen bondings and C-H...pi interactions. The
      C1-O1 = 1.287(4) (density functional theory, DFT, 1.311) and C6-N1 = 1.320(4)
      (DFT, 1.353) A and intraring bond distances associated with the sensitive quinine
      (Q) moiety along with the azo(pap) bond distances, N3-N4 = 1.278(4) (DFT, 1.297)
      and N6-N7 = 1.271(4) (DFT, 1.289) A, in 2(+) justify the [(pap)(2)Ru(II)(Q(*
      ))](+) valence configuration at the native state of 1(+)-4(+). Consequently,
      Mulliken spin densities on Q, pap, and Ru in 2(+) are calculated to be 0.8636,
      0.1040, and 0.0187, respectively, and 1(+)-4(+) exhibit free radical sharp EPR
      spectra and one weak and broad transition around 1000 nm in CH(3)CN due to
      interligand transition involving a singly occupied molecular orbital (SOMO) of
      Q(*-) and the vacant pi* orbital of pap. Compounds 1(+)-4(+) undergo a quasi
      reversible oxidation and three successive reductions. The valence structure of
      the electron paramagnetic resonance (EPR)-inactive oxidized state in 1(2+)-4(2+)
      has been established as [(pap)(2)Ru(II)(Q degrees )](2+) instead of the alternate
      formalism of antiferromagnetically coupled [(pap)(2)Ru(III)(Q(*-))](2+) on the
      basis of the DFT calculations on the optimized 2(+), which predict that the
      singly occupied molecular orbital is primarily composed of Q with 77%
      contribution. Accordingly, the optimized structure of 2(2+) predicts shorter C1
      O1 (1.264) and C6-N1 (1.317 A) distances and longer Ru1-O1 (2.080) and Ru1-N1
      (2.088 A) distances. Compounds 1(2+)-4(2+) exhibit the lowest energy transitions
      around 600 nm, corresponding to Ru(dpi)/Q(pi) --> pap(pi*). The presence of two
      sets of strongly pi-acceptor ligands, pap and Q, in 1(2+)-4(2+) stabilizes the
      Ru(II) state to a large extent such that the further oxidation of {Ru(II)-Q
      degrees } --> {Ru(III)-Q degrees } has not been detected within +2.0 V versus a
      saturated calomel electrode. The EPR-inactive reduced states 1-4 have been
      formulated as [(pap)(2)Ru(II)(Q(2-))] over the antiferromagnetically coupled
      alternate configuration, [(pap)(pap(*-))Ru(II)(Q(*-))]. The optimized structure
      of 2 predicts sensitive C1-O1 and C6-N1 bond distances of 1.337 and 1.390 A,
      respectively, close to the doubly reduced Q(2-) state, whereas the N horizontal
      lineN distances of pap, N3-N4 = 1.299 and N6-N7 = 1.306 A, remain close to the
      neutral state. In corroboration with the doubly reduced Q(2-) state, 1-4 exhibit
      a moderately strong interligand pi(Q(2-)) --> pi*(pap) transition in the near-IR
      region near 1300 nm. The subsequent two reductions are naturally centered around
      the azo functions of the pap ligands.

PMID- 19769397
TI  - Solutions for the developing world.

PMID- 19769399
TI  - A conversation with Prof. Mildred Dresselhaus: a career in carbon nanomaterials.
      Interview by Paul S Weiss.

PMID- 19769400
TI  - The nanomaterial characterization bottleneck.
AB  - The future of nanotechnology rests upon approaches to making new, useful
      nanomaterials and testing them in complex systems. Currently, the advance from
      discovery to application is constrained in nanomaterials relative to a mature
      market, as seen in molecular and bulk matter. To reap the benefits of
      nanotechnology, improvements in characterization are needed to increase
      throughput as creativity outpaces our ability to confirm results. The
      considerations of research, commerce, and regulation are part of a larger
      feedback loop that illustrates a mutual need for rapid, easy, and standardized
      characterization of a large property matrix. Now, we have an opportunity and a
      need to strike a new balance that drives higher quality research, simplifies
      commercial exploitation, and allows reasoned regulatory approaches.

PMID- 19769401
TI  - An inside-out approach to storing electrostatic energy.
AB  - The ability to achieve high-energy densities is the central challenge in energy
      storage and recovery. A promising strategy for increasing energy storage is to
      use high-performance dielectric materials, such as highly polarizable
      nanoparticles or polymers, or nanocomposites of the two. In this issue, Kim et
      al. use a molecular coating and clever chemistry to combine oxide nanoparticles
      with a polymer matrix, thereby producing an improved nanocomposite dielectric.
      Some advantages and challenges of using nanocomposites as improved dielectric
      materials are presented in this Perspective.

PMID- 19769403
TI  - Etching of graphene devices with a helium ion beam.
AB  - We report on the etching of graphene devices with a helium ion beam, including in
      situ electrical measurement during lithography. The etching process can be used
      to nanostructure and electrically isolate different regions in a graphene device,
      as demonstrated by etching a channel in a suspended graphene device with etched
      gaps down to about 10 nm. Graphene devices on silicon dioxide (SiO(2)) substrates
      etch with lower He ion doses and are found to have a residual conductivity after
      etching, which we attribute to contamination by hydrocarbons.

PMID- 19769402
TI  - Exposure to titanium dioxide nanomaterials provokes inflammation of an in vitro
      human immune construct.
AB  - Nanoparticle technology is undergoing significant expansion largely because of
      the potential of nanoparticles as biomaterials, drug delivery vehicles, cancer
      therapeutics, and immunopotentiators. Incorporation of nanoparticle technologies
      for in vivo applications increases the urgency to characterize nanomaterial
      immunogenicity. This study explores titanium dioxide, one of the most widely
      manufactured nanomaterials, synthesized into its three most common
      nanoarchitectures: anatase (7-10 nm), rutile (15-20 nm), and nanotube (10-15 nm
      diameters, 70-150 nm length). The fully human autologous MIMIC immunological
      construct has been utilized as a predictive, nonanimal alternative to diagnose
      nanoparticle immunogenicity. Cumulatively, treatment with titanium dioxide
      nanoparticles in the MIMIC system led to elevated levels of proinflammatory
      cytokines and increased maturation and expression of costimulatory molecules on
      dendritic cells. Additionally, these treatments effectively primed activation and
      proliferation of naive CD4(+) T cells in comparison to dendritic cells treated
      with micrometer-sized (>1 microm) titanium dioxide, characteristic of an in vivo
      inflammatory response.

PMID- 19769404
TI  - Chemically linked AuNP-alkane network for enhanced photoemission and field
      emission.
AB  - Size and ligand effects are the basis for the novel properties and applications
      of metallic nanoparticles (NPs) in nanoelectronics, optoelectronics, and
      biotechnology. This work reports the first observation of enhanced photoelectron
      emission from metallic Au NPs ligated by alkanethiols. The enhancement is based
      on a conceptually new mechanism: the AuNP provides electrons while the alkane
      ligand emits electrons due to its low or negative electron affinity. Moreover,
      the AuNP-ligand chemical bonding is found to significantly facilitate the
      transmission of photoexcited electrons from the AuNP to the ligand emitter.
      Consequently the smooth NP film, which is a typical low-aspect-ratio two
      dimensional structure, exhibits strong and stable field emission behavior under
      photoillumination conditions. The photoenhanced field emission is related to the
      interband and surface plasmon transitions in AuNPs, and a photoenhancement factor
      of up to approximately 300 is observed for the AuNP-based field emission. This is
      highly remarkable because field emission is often based on one-dimensional, high
      aspect-ratio nanostructures (e.g., nanotubes and nanowires) with geometrical
      field enhancement effect. The chemical linkage of electron-supplying AuNP and
      electron-emitting alkane ligand represents a fundamentally new mechanism for
      efficient photoexcitation and emission. Being low-temperature/solution
      processable, and inkjet printable, AuNPs may be a flexible material system for
      optoelectronic applications such as photodetection and photoenhanced field
      emission.

PMID- 19769405
TI  - Observing self-assembled lipid nanoparticles building order and complexity
      through low-energy transformation processes.
AB  - Future nanoscale soft matter design will be driven by the biological paradigms of
      hierarchical self-assembly and long-lived nonequilibrium states. To reproducibly
      control the low-energy self-assembly of nanomaterials for the future, we must
      first learn the lessons of biology. Many cellular organelles exhibit highly
      ordered cubic membrane structures. Determining the mechanistic origins of such
      lipid organelle complexity has been elusive. We report the first observation of
      the complete sequence of major transformations in the conversion from a 1D
      lamellar membrane to 3D inverse bicontinuous cubic nanostructure.
      Characterization was enabled by adding a steric stabilizer to dispersions of
      lipid nanoparticles which increased the lifetime of very short-lived
      nonequilibrium intermediate structures. By using synchrotron small-angle X-ray
      scattering and cryo-transmission electron microscopy we observed and
      characterized initial lipid bilayer contacts and stalk formation, followed by
      membrane pore development, pore evolution into 2D hexagonally packed lattices,
      and finally creation of 3D bicontinuous cubic structures.

PMID- 19769406
TI  - Understanding self-poisoning phenomenon in crystal growth of short-chain
      polymers.
AB  - Flexible polymers crystallize with chain folding, which shows a unique phenomenon
      called self-poisoning. As a result, minima in crystal growth rates of strictly
      monodisperse short-chain polymers are observed near the temperatures of
      transitions from extended-chain to once-folded-chain growth, from once-folded to
      twice-folded growth, etc. We employed dynamic Monte Carlo simulation of lattice
      polymers to visualize such transitions in molecular details. We observed a rate
      crossover between chain extension and lateral growth of polymer lamellar crystals
      at the wedge-shaped growth front, resulting in a rate minimum around the melting
      point of the metastable once-folded lamellar crystal. The rate minimum can be
      interpreted as due to the dependence of crystal growth rates on the excess
      crystal thickness beyond the minimum stable thickness. Furthermore, during
      crystal thickening, numerous molten chains are shown to be sucked into the
      lamellar crystals through the basal planes, demonstrating an important source of
      crystallinity from secondary crystallization lagging behind the crystal growth
      front.

PMID- 19769407
TI  - Insights into the molecular determinants of proton inhibition in an acid
      inactivated degenerins and mammalian epithelial Na(+) channel.
AB  - Mammalian ASIC channels of the DEG/ENaC superfamily are gated by extracellular
      protons and function to mediate touch and pain sensitivity, learning and memory,
      and fear conditioning. The recently solved crystal structure of chicken ASIC1a
      and preliminary functional studies suggested that a highly negatively charged
      pocket in the extracellular domain of the channel might be the primary proton
      binding domain. However, more recent extensive mutagenesis analysis paints a more
      complex mechanism of channel gating, involving binding of protons at sites
      immediately after the first transmembrane domain (TM1) and displacement of
      inhibitory Ca(2+) ions from the acidic pocket in the extracellular domain and
      from another Ca(2+) binding site at the mouth of the pore. We recently identified
      and functionally characterized Caenorhabditis elegans ACD-1, the first acid
      inactivated DEG/ENaC channel. ACD-1 is expressed in C. elegans amphid glia and
      functions with neuronal DEG/ENaC channel DEG-1 to mediate acid avoidance and
      chemotaxis to the amino acid lysine. The post-TM1 residues that were proposed to
      bind protons in ASIC1a are not conserved in ACD-1, but some of the amino acids
      constituting the acidic pocket are. However, ACD-1 proton sensitivity is
      completely independent from extracellular Ca(2+), and protons appear to bind the
      channel in a less cooperative manner. We thus wondered if residues in the acidic
      pocket might contribute to ACD-1 acid sensitivity. We show here that while ACD-1
      sensitivity to extracellular protons is influenced by mutations in the acidic
      pocket, other sites are likely to participate. We also report that one histidine
      at the base of the thumb and residues in the channel pore influence proton
      inhibition in a voltage-independent manner, suggesting that they affect the
      coupling of proton binding with the gating rather than proton binding itself. We
      conclude that ACD-1 inhibition by protons is likely mediated by binding of proton
      ions to multiple sites throughout the extracellular domain of the channel. Our
      data also support a model in which residues in the acidic pocket contribute to
      determining the channel state perhaps by changing the strength of the interaction
      between adjacent thumb and finger domains.

PMID- 19769408
TI  - Allosteric control of regulated scaffolding in membrane-associated guanylate
      kinases.
AB  - Membrane-associated guanylate kinases (MAGUKs) organize protein complexes at
      specific cellular sites by regulating interactions with their COOH-terminal
      guanylate kinase-like domains (GKs). Negative regulation of MAGUK GKs by an
      adjacent Src homology 3 domain (SH3) is critical for function, yet the mechanism
      is poorly understood. To gain insight into this process, we investigated SH3
      regulation of the Discs large (Dlg) GK. Mutational analysis revealed that the
      binding site of the SH3-inhibited GK ligand GukHolder (GukH) is opposite the SH3
      interacting surface, indicating that the SH3 does not directly occlude GukH
      binding. We screened for constitutively active SH3GK variants using yeast two
      hybrid and a cell polarity/mitotic spindle orientation assay. Residues in both
      the SH3 and GK are required to maintain SH3GK inhibition, including those distant
      from both the SH3-GK and GK-GukH interaction sites. Activating mutations do not
      alter the ability of the SH3 and GK to interact in trans. On the basis of these
      observations, we propose that the SH3 modulates GK allostery to control its
      function.

PMID- 19769410
TI  - Amino acid Asp181 of 5'-flap endonuclease 1 is a useful target for
      chemotherapeutic development.
AB  - DNA alkylation-induced damage is one of the most efficacious anticancer
      therapeutic strategies. Enhanced DNA alkylation and weakened DNA repair capacity
      in cancer cells are responsible for the effectiveness of DNA-alkylating
      therapies. 5'-Flap endonuclease 1 (Fen1) is an important enzyme involved in base
      excision repair (BER), specifically in long-patch BER (LP-BER). Using the site
      directed mutagenesis approach, we have identified an important role for amino
      acid Asp181 of Fen1 in its endonuclease activity. Asp181 is thought to be
      involved in Mg(2+) binding in the active site. Using structure-based molecular
      docking of Fen1 targeted to its metal binding pocket M2 (Mg(2+) site), we have
      identified a potent low-molecular weight inhibitor (LMI, NSC-281680) that
      efficiently blocks LP-BER. In this study, we have demonstrated that the
      interaction of this LMI with Fen1 blocked its endonuclease activity, thereby
      blocking LP-BER and enhancing the cytotoxic effect of DNA-alkylating agent
      Temozolomide (TMZ) in mismatch repair (MMR)-deficient and MMR-proficient colon
      cancer cells. The results further suggest that blockade of LP-BER by NSC-281680
      may bypass other drug resistance mechanisms such as mismatch repair (MMR)
      defects. Therefore, our findings provide groundwork for the development of highly
      specific and safer structure-based small molecular inhibitors targeting the BER
      pathway, which can be used along with existing chemotherapeutic agents, like TMZ,
      as combination therapy for the treatment of colorectal cancer.

PMID- 19769411
TI  - Differential secreted proteome approach in murine model for candidate biomarker
      discovery in colon cancer.
AB  - The complexity and heterogeneity of the plasma proteome have presented
      significant challenges in the identification of protein changes associated with
      tumor development. We used cell culture as a model system and identified
      differentially expressed, secreted proteins which may constitute serological
      biomarkers. A stable isotope labeling by amino acids in cell culture (SILAC)
      approach was used to label the entire secreted proteomes of the CT26 murine colon
      cancer cell line and normal young adult mouse colon (YAMC) cell line, thereby
      creating a stable isotope labeled proteome (SILAP) standard. This SILAP standard
      was added to unlabeled murine CT26 colon cancer cell or normal murine YAMC colon
      epithelial cell secreted proteome samples. A multidimensional approach combining
      isoelectric focusing (IEF), strong cation exchange (SCX) followed by reversed
      phase liquid chromatography was used for extensive protein and peptide
      separation. A total of 614 and 929 proteins were identified from the YAMC and
      CT26 cell lines, with 418 proteins common to both cell lines. Twenty highly
      abundant differentially expressed proteins from these groups were selected for
      liquid chromatography-multiple reaction monitoring/mass spectrometry (LC-MRM/MS)
      analysis in sera. Differential secretion into the serum was observed for several
      proteins when Apc(min) mice were compared with control mice. These findings were
      then confirmed by Western blot analysis.

PMID- 19769412
TI  - The evolution of sport psychiatry, circa 2009.
AB  - Over the past three decades, the world of both amateur and professional sports
      has expanded greatly and become more complex. In part related to these changes -
      and relatively unknown to sports medicine practitioners - the field of sport
      psychiatry has steadily evolved and grown. This paper focuses on what these
      changes have been. A sport psychiatrist is a physician-psychiatrist who diagnoses
      and treats problems, symptoms and/or disorders associated with an athlete, with
      their family/significant others, with their team, or with their sport, including
      spectators/fans. The primary aims of the specialty are to (i) optimize health,
      (ii) improve athletic performance, and (iii) manage psychiatric symptoms or
      disorders. The training includes medical training to provide knowledge and skills
      unique to physicians; psychiatric training to provide knowledge and skills
      inherent in that field, and training and/or experience in sport psychiatry to
      provide knowledge and skills about psychiatric aspects of sports. The sport
      psychiatrist first makes an individual, family-systems and phenomenological
      diagnosis of the clinical situation. Based on this evaluation, he sets goals for
      not only the athlete, but also for significant others involved. He delivers
      treatment based on the psychiatric disorder or problem using a combination of
      medication, psychotherapy or self-help group interventions plus strategies
      targeted to specific sport performance issues. Evolution of the International
      Society of Sport Psychiatry as well as the field, including incorporation into
      school and professional team sports, is described along with a 'typical day' for
      a sport psychiatrist. Case examples, a training curriculum and core literature
      are included.

PMID- 19769413
TI  - Aerobic conditioning for team sport athletes.
AB  - Team sport athletes require a high level of aerobic fitness in order to generate
      and maintain power output during repeated high-intensity efforts and to recover.
      Research to date suggests that these components can be increased by regularly
      performing aerobic conditioning. Traditional aerobic conditioning, with minimal
      changes of direction and no skill component, has been demonstrated to effectively
      increase aerobic function within a 4- to 10-week period in team sport players.
      More importantly, traditional aerobic conditioning methods have been shown to
      increase team sport performance substantially. Many team sports require the
      upkeep of both aerobic fitness and sport-specific skills during a lengthy
      competitive season. Classic team sport trainings have been shown to evoke
      marginal increases/decreases in aerobic fitness. In recent years, aerobic
      conditioning methods have been designed to allow adequate intensities to be
      achieved to induce improvements in aerobic fitness whilst incorporating movement
      specific and skill-specific tasks, e.g. small-sided games and dribbling circuits.
      Such 'sport-specific' conditioning methods have been demonstrated to promote
      increases in aerobic fitness, though careful consideration of player skill
      levels, current fitness, player numbers, field dimensions, game rules and
      availability of player encouragement is required. Whilst different conditioning
      methods appear equivalent in their ability to improve fitness, whether sport
      specific conditioning is superior to other methods at improving actual game
      performance statistics requires further research.

PMID- 19769415
TI  - Shoulder muscle activity and function in common shoulder rehabilitation
      exercises.
AB  - The rotator cuff performs multiple functions during shoulder exercises, including
      glenohumeral abduction, external rotation (ER) and internal rotation (IR). The
      rotator cuff also stabilizes the glenohumeral joint and controls humeral head
      translations. The infraspinatus and subscapularis have significant roles in
      scapular plane abduction (scaption), generating forces that are two to three
      times greater than supraspinatus force. However, the supraspinatus still remains
      a more effective shoulder abductor because of its more effective moment arm. Both
      the deltoids and rotator cuff provide significant abduction torque, with an
      estimated contribution up to 35-65% by the middle deltoid, 30% by the
      subscapularis, 25% by the supraspinatus, 10% by the infraspinatus and 2% by the
      anterior deltoid. During abduction, middle deltoid force has been estimated to be
      434 N, followed by 323 N from the anterior deltoid, 283 N from the subscapularis,
      205 N from the infraspinatus, and 117 N from the supraspinatus. These forces are
      generated not only to abduct the shoulder but also to stabilize the joint and
      neutralize the antagonistic effects of undesirable actions. Relatively high force
      from the rotator cuff not only helps abduct the shoulder but also neutralizes the
      superior directed force generated by the deltoids at lower abduction angles. Even
      though anterior deltoid force is relatively high, its ability to abduct the
      shoulder is low due to a very small moment arm, especially at low abduction
      angles. The deltoids are more effective abductors at higher abduction angles
      while the rotator cuff muscles are more effective abductors at lower abduction
      angles. During maximum humeral elevation the scapula normally upwardly rotates 45
      55 degrees, posterior tilts 20-40 degrees and externally rotates 15-35 degrees.
      The scapular muscles are important during humeral elevation because they cause
      these motions, especially the serratus anterior, which contributes to scapular
      upward rotation, posterior tilt and ER. The serratus anterior also helps
      stabilize the medial border and inferior angle of the scapular, preventing
      scapular IR (winging) and anterior tilt. If normal scapular movements are
      disrupted by abnormal scapular muscle firing patterns, weakness, fatigue, or
      injury, the shoulder complex functions less efficiency and injury risk increases.
      Scapula position and humeral rotation can affect injury risk during humeral
      elevation. Compared with scapular protraction, scapular retraction has been shown
      to both increase subacromial space width and enhance supraspinatus force
      production during humeral elevation. Moreover, scapular IR and scapular anterior
      tilt, both of which decrease subacromial space width and increase impingement
      risk, are greater when performing scaption with IR ('empty can') compared with
      scaption with ER ('full can'). There are several exercises in the literature that
      exhibit high to very high activity from the rotator cuff, deltoids and scapular
      muscles, such as prone horizontal abduction at 100 degrees abduction with ER,
      flexion and abduction with ER, 'full can' and 'empty can', D1 and D2 diagonal
      pattern flexion and extension, ER and IR at 0 degrees and 90 degrees abduction,
      standing extension from 90-0 degrees , a variety of weight-bearing upper
      extremity exercises, such as the push-up, standing scapular dynamic hug, forward
      scapular punch, and rowing type exercises. Supraspinatus activity is similar
      between 'empty can' and 'full can' exercises, although the 'full can' results in
      less risk of subacromial impingement. Infraspinatus and subscapularis activity
      have generally been reported to be higher in the 'full can' compared with the
      'empty can', while posterior deltoid activity has been reported to be higher in
      the 'empty can' than the 'full can'.

PMID- 19769414
TI  - The exercise-induced stress response of skeletal muscle, with specific emphasis
      on humans.
AB  - Skeletal muscle adapts to the stress of contractile activity via changes in gene
      expression to yield an increased content of a family of highly conserved
      cytoprotective proteins known as heat shock proteins (HSPs). These proteins
      function to maintain homeostasis, facilitate repair from injury and provide
      protection against future insults. The study of the exercise-induced production
      of HSPs in skeletal muscle is important for the exercise scientist as it may
      provide a valuable insight into the molecular mechanisms by which regular
      exercise can provide increased protection against related and non-related
      stressors. As molecular chaperones, HSPs are also fundamental in facilitating the
      cellular remodelling processes inherent to the training response. Whilst the
      exercise-induced stress response of rodent skeletal muscle is relatively well
      characterized, data from humans are more infrequent and less insightful. Data
      indicate that acute endurance- and resistance-type exercise protocols increase
      the muscle content of ubiquitin, alphaB-crystallin, HSP27, HSP60, HSC70 and
      HSP70. Although increased HSP transcription occurs during exercise, immediately
      post-exercise or several hours following exercise, time-course studies using
      western blotting techniques have typically demonstrated a significant increase in
      protein content is only detectable within 1-2 days following the exercise stress.
      However, comparison amongst studies is complicated by variations in exercise
      protocol (mode, intensity, duration, damaging, non-damaging), muscle group
      examined, predominant HSP measured and, perhaps most importantly, differences in
      subject characteristics both within and between studies (training status, recent
      activity levels, nutritional status, age, sex, etc.). Following 'non-damaging'
      endurance-type activities (exercise that induces no overt structural and
      functional damage to the muscle), the stress response is thought to be mediated
      by redox signalling (transient and reversible oxidation of muscle proteins) as
      opposed to increases in contracting muscle temperature per se. Following
      'damaging' forms of exercise (exercise that induces overt structural and
      functional damage to the muscle), the stress response is likely initiated by
      mechanical damage to protein structure and further augmented by the secondary
      damage associated with inflammatory processes occurring several days following
      the initial insult. Exercise training induces an increase in baseline HSP levels,
      which is dependent on a sustained and currently unknown dose of training and also
      on the individual's initial training status. Furthermore, trained subjects
      display an attenuated or abolished stress response to customary exercise
      challenges, likely due to adaptations of baseline HSP levels and the antioxidant
      system. Whilst further fundamental work is needed to accurately characterize the
      exercise-induced stress response in specific populations following varying
      exercise protocols, exercise scientists should also focus their efforts on
      elucidating the precise biological significance of the exercise-induced induction
      of HSPs. In addition to their potential cytoprotective properties, the role of
      HSPs in modulating cell signalling pathways related to both exercise adaptation
      and health and disease also needs further investigation. As a non-pharmacological
      intervention, exercise and the associated up-regulation of HSPs and the possible
      correction of maladapted pathways may therefore prove effective in providing
      protection against protein misfolding diseases and in preserving muscle function
      during aging.

PMID- 19769419
TI  - Can continuing education ever be harmful?

PMID- 19769416
TI  - Endurance athletes' stroke volume response to progressive exercise: a critical
      review.
AB  - Untrained subjects typically demonstrate a plateau in stroke volume beyond the
      early stages of an acute bout of progressive exercise. Some studies have
      indicated that the stroke volume pattern in highly trained endurance athletes may
      differ, continuing to rise progressively to the point of maximal exercise. This
      suggests that the mechanism for generating cardiac output in these athletes may
      be influenced by cardiac functional factors, particularly augmented diastolic
      filling. This review of studies assessing stroke volume changes with exercise in
      athletes reveals a wide disparity of reported patterns, ranging from those
      indicating a decline, to stable values (a true plateau), to a progressive
      increase to exhaustion of over 40%. Differences in testing methodology might help
      to explain these variable results, but which pattern truly reflects that expected
      in highly trained endurance athletes remains uncertain. Ancillary data suggest
      that if a non-plateau of stroke volume is typical of athletes, augmented
      diastolic filling might be the responsible mechanism. However, it is not clear
      whether this might reflect superior upstream (atrial pressure/volume) or
      downstream (ventricular diastolic function, compliance) factors.

PMID- 19769420
TI  - Psychosedation with dexmedetomidine hydrochloride during minor oral surgery.
AB  - We performed intravenous sedation with dexmedetomidine hydrochloride during minor
      oral surgery and compared this agent with propofol. Patients were randomly
      divided into 2 groups: dexmedetomidine hydrochloride (D) and propofol (P) groups.
      In Group D, systolic blood pressure (SBP) increased immediately after the start
      of initial loading, although no significant differences were noted. Both SBP and
      diastolic blood pressure (DBP) gradually decreased during maintenance
      administration and were significantly lower than pretreatment values. The heart
      rate decreased immediately after the start of administration and was
      significantly lower during both initial loading and maintenance administration;
      the heart rate was also significantly lower than that in Group P. In Group D,
      arterial blood oxygen saturation (SpO2) significantly decreased after the
      sedation level reached an optimum level until the end of administration. The
      bispectral index (BIS) value gradually decreased during initial loading. At the
      optimal sedation level, it decreased to 80 to 85. During maintenance
      administration, marked changes were observed in this parameter. No marked
      differences in amnestic effects and comfort were noted between the 2 groups. If
      the sedation level can be evaluated accurately via another objective method,
      intravenous sedation with dexmedetomidine hydrochloride may be useful in dental
      treatment.

PMID- 19769422
TI  - Perioperative management of the glucose-6-phosphate dehydrogenase deficient
      patient: a review of literature.
AB  - Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymatic
      disorder of red blood cells in humans. It is estimated that about 400 million
      people are affected by this deficiency. The G6PD enzyme catalyzes the first step
      in the pentose phosphate pathway, leading to antioxidants that protect cells
      against oxidative damage. A G6PD-deficient patient, therefore, lacks the ability
      to protect red blood cells against oxidative stresses from certain drugs,
      metabolic conditions, infections, and ingestion of fava beans. The following is a
      literature review, including disease background, pathophysiology, and clinical
      implications, to help guide the clinician in management of the G6PD-deficient
      patient. A literature search was conducted in the following databases: PubMed,
      The Cochrane Library, Web of Science, OMIM, and Google; this was supplemented by
      a search for selected authors. Keywords used were glucose-6-phosphate
      dehydrogenase (G6PD) deficiency, anesthesia, analgesia, anxiolysis, management,
      favism, hemolytic anemia, benzodiazepines, codeine, codeine derivatives,
      ketamine, barbiturates, propofol, opioids, fentanyl, and inhalation anesthetics.
      Based on titles and abstracts, 23 papers and 1 website were identified. The
      highest prevalence of G6PD is reported in Africa, southern Europe, the Middle
      East, Southeast Asia, and the central and southern Pacific islands; however, G6PD
      deficiency has now migrated to become a worldwide disease. Numerous drugs,
      infections, and metabolic conditions have been shown to cause acute hemolysis of
      red blood cells in the G6PD-deficient patient, with the rare need for blood
      transfusion. Benzodiazepines, codeine/codeine derivatives, propofol, fentanyl,
      and ketamine were not found to cause hemolytic crises in the G6PD-deficient
      patient. The most effective management strategy is to prevent hemolysis by
      avoiding oxidative stressors. Thus, management for pain and anxiety should
      include medications that are safe and have not been shown to cause hemolytic
      crises, such as benzodiazepines, codeine/codeine derviatives, propofol, fentanyl,
      and ketamine. The authors of this article make 5 particular recommendations: (1)
      Anyone suspected of G6PD deficiency should be screened; (2) exposure to oxidative
      stressors in these individuals should be avoided; (3) these patients should be
      informed of risks along with signs and symptoms of an acute hemolytic crisis; (4)
      the clinician should be able to identify both laboratory and clinical signs of
      hemolysis; and finally, (5) if an acute hemolytic crisis is identified, the
      patient should be admitted for close observation and care.

PMID- 19769421
TI  - Comparative efficacy of 2 topical anesthetics for the placement of orthodontic
      temporary anchorage devices.
AB  - This study compared the effectiveness of topical benzocaine 20% versus a
      combination of lidocaine, tetracaine, and phenylephrine in providing sufficient
      analgesia for the placement of orthodontic temporary anchorage devices (TADs).
      The 2 topical anesthetics were tested against each other bilaterally using a
      randomized, double-blind, crossover design. The agents were left in place for the
      amount of time prescribed by the manufacturer. The TAD was then placed, and each
      subject rated the degree of pain on a Heft-Parker visual analogue scale. A pulse
      oximeter was used to record the preoperative and postoperative pulse rates.
      Statistically significant differences in perceived pain (P < .05) and success
      rate (P < .01) between drugs were seen, but no significant difference in pulse
      rate change between the topical anesthetics was observed (P > .05). It was
      concluded that when the efficacy of topical benzocaine and of a combination
      product was compared as the sole anesthetic to facilitate acceptable pain control
      for placement of orthodontic temporary anchorage devices, the combination product
      was considerably more efficacious.

PMID- 19769423
TI  - Preoperative medical evaluation: part 1: general principles and cardiovascular
      considerations.
AB  - A thorough assessment of a patient's medical status is standard practice when
      dental care is provided. Although this is true for procedures performed under
      local anesthesia alone, the information gathered may be viewed somewhat
      differently if the dentist is planning to use sedation or general anesthesia as
      an adjunct to dental treatment. This article is the first of a 2-part sequence
      and will address general principles and cardiovascular considerations. A second
      article will address pulmonary, metabolic, and miscellaneous disorders.

PMID- 19769424
TI  - Executive functioning, irritability, and alcohol-related aggression.
AB  - The purpose of this investigation was to examine (a) whether irritability
      mediates the relation between executive functioning (EF) and alcohol-related
      aggression and (b) whether the alcohol-aggression relation is better explained by
      the interactive effects of EF and irritability above and beyond the effects of
      either variable alone. EF was measured using seven well-established
      neuropsychological tests. Irritability was assessed with the Caprara Irritability
      Scale. Participants were 313 male and female social drinkers between 21 and 35
      years of age. Following the consumption of an alcohol or a placebo beverage,
      participants were tested on a laboratory aggression task in which electric shocks
      were given to and received from a fictitious opponent under the guise of a
      competitive reaction-time task. Aggression was operationalized as the shock
      intensities administered to the fictitious opponent. Results indicated that
      irritability successfully mediated the relation between EF and intoxicated
      aggression for men only. Despite the fact that irritability and EF both
      independently moderated the alcohol-aggression relation in previous studies, no
      significant interaction for their combined effect was detected here. The findings
      are discussed, in part, within a cognitive neoassociationistic framework for
      aggressive behavior.

PMID- 19769425
TI  - Selection and socialization of risky drinking during the college transition: The
      importance of microenvironments associated with specific living units.
AB  - Risky drinking among college students differs as a function of living types, with
      living at Greek houses as a major risk factor. Both self-selection based on prior
      drinking and socialization through living environments have been shown to account
      for this association. However, it is not clear whether selection and
      socialization processes occur as a function of specific living units within
      living types. Multilevel models using a prospective sample of incoming college
      students (N = 2,392) demonstrated that (1) precollege drinking based selection
      into specific living units occurred within both fraternity houses and residence
      halls (beyond selection into the Greek system in general) and (2) socialization
      of extremely risky drinking among certain fraternity houses was greater than
      other houses (beyond greater socialization of living at fraternity houses than
      residence halls in general). Living unit-level precollege correlates (i.e.,
      college attendance motives and cigarette use) and college correlates (i.e., peer
      drinking norms and alcohol availability) accounted for most of the selection and
      socialization effects. These findings highlight the importance of micro
      environments associated with specific living units in risky drinking during the
      college transition.

PMID- 19769426
TI  - Alcohol abuse and dependence symptoms: a multidimensional model of common and
      specific etiology.
AB  - This study tested a theoretical model hypothesizing differential pathways from 5
      predictors to alcohol abuse and dependence symptoms. The participants were
      college students (N = 2,270) surveyed on 2 occasions in a 6-month prospective
      design. Social norms, perceived utility of alcohol use, and family history of
      alcohol problems were indirectly associated with Time 2 abuse and dependence
      symptoms through influencing level of alcohol consumption. Poor behavioral
      control had a direct effect on alcohol abuse but not on dependence symptoms at
      Time 2, whereas affective lability exhibited a direct prospective effect on
      alcohol dependence but not on abuse symptoms. A multigroup analysis showed that
      high levels of poor control increased the strength of paths from both consumption
      level and affective lability to abuse symptoms. Implications for prevention of
      alcohol problems among college students are discussed.

PMID- 19769427
TI  - Reasons for abstaining or limiting drinking: a developmental perspective.
AB  - The cross-sectional and longitudinal relations between reasons for abstaining or
      limiting drinking (RALD) and abstention were examined in a 16-year longitudinal
      study (N = 489) of college students with and without a family history of alcohol
      problems. Results indicated that RALD based upon upbringing or religiosity were
      associated with increased rates of abstention, whereas RALD based upon perceived
      or experienced negative consequences of drinking were associated with lower rates
      of abstention and increased alcohol consumption among drinkers. In addition,
      changes in RALD over time coincided with alcohol consumption transitions.
      Abstainers who began drinking after turning 21 reported a decrease in the
      importance of RALD associated with loss of control and upbringing or religiosity
      compared to abstainers who continued to abstain after turning 21. Conversely,
      drinkers who began abstaining after leaving college reported an increase in the
      importance of RALD associated with loss of control and upbringing or religiosity
      compared to drinkers who continued to drink after leaving college. Examining the
      reciprocal influences of RALD on drinking outcomes extends previous research and
      may inform prevention and intervention programs among college drinkers.

PMID- 19769428
TI  - Drinking to cope as a statistical mediator in the relationship between suicidal
      ideation and alcohol outcomes among underage college drinkers.
AB  - Etiological models of alcohol use that highlight the role of negative affect and
      depression have not been applied to the association of suicidality and alcohol
      use. The authors examined whether a motivational model of alcohol use could be
      applied to understand the relationship between suicidal ideation and alcohol
      outcomes in a sample of underage college drinkers who had a history of passive
      suicidal ideation (n = 91). In this cross-sectional study, regression analyses
      were conducted to examine whether drinking to cope with negative affect
      statistically mediated or was an intervening variable in the association between
      suicidal ideation and alcohol outcomes. Results revealed that drinking to cope
      was a significant intervening variable in the relationships between suicidal
      ideation and alcohol consumption, heavy episodic drinking, and alcohol problems,
      even while controlling for depression. These results suggest that the
      relationship between suicidal ideation and alcohol outcomes may be due to
      individuals using alcohol to regulate or escape the distress associated with
      suicidal ideation. Consideration of alcohol-related models can improve the
      conceptualization of research on suicidality and alcohol use.

PMID- 19769430
TI  - A new decisional balance measure of motivation to change among at-risk college
      drinkers.
AB  - In this study, an open-ended decisional balance worksheet was used to elicit self
      generated pros and cons of current drinking and reducing drinking, which were
      then quantified to create a decisional balance proportion (DBP) reflecting
      movement toward change (i.e., counts of pros of reducing drinking and cons of
      current drinking to all decisional balance fields). This study's goal was to
      examine the convergent, discriminant, and predictive validity of the DBP as a
      measure of motivation to change. Participants were college students (N = 143) who
      reported having engaged in weekly heavy, episodic drinking and who had
      participated in a larger randomized clinical trial of brief motivational
      interventions (K. B. Carey, M. P. Carey, S. A. Maisto, & J. M. Henson, 2006).
      Findings indicated partial support for convergent and discriminant validity of
      the DBP. Compared with Likert scale measures of decisional balance and readiness
      to change, DBP scores reflecting greater movement toward change best predicted
      reductions in heavy drinking quantity and frequency and experience of alcohol
      related consequences, although some of these effects decayed by the 12-month
      follow-up. Findings suggest that the DBP is a valid measure of motivation to
      change among at-risk college drinkers.

PMID- 19769429
TI  - ALDH2, ADH1B and alcohol expectancies: integrating genetic and learning
      perspectives.
AB  - The present study evaluated associations of ALDH2 and ADH1B genotypes with
      alcohol expectancies and drinking behavior in a sample of Asian American young
      adults. In addition to assessing global alcohol expectancies, the authors
      developed a measure of physiological expectancies to evaluate an expectancy
      phenotype specific to the mechanism by which ALDH2 and ADH1B variations
      presumably influence drinking behavior. Compared with individuals with the
      ALDH2*1/*1 genotype, those with the ALDH2*2 allele reported greater negative
      alcohol expectancies, greater expectancies for physiological effects of alcohol
      and lower rates of alcohol use. ADH1B was not associated with alcohol
      expectancies or drinking behavior. Hierarchical models showed that demographic
      factors, ALDH2 genotype, and expectancy variables explained unique variance in
      drinking outcomes. Mediation tests showed significant indirect effects of ALDH2
      on drinking frequency and peak lifetime consumption through expectancies. These
      results provide support for influences of genetic factors and alcohol sensitivity
      on alcohol-related learning and suggest the importance of developing
      biopsychosocial models of drinking behavior in Asian Americans.

PMID- 19769431
TI  - Does drinking lead to sex? Daily alcohol-sex behaviors and expectancies among
      college students.
AB  - A within-person multilevel approach was used to model the links between alcohol
      use and sexual behavior among first-year college students, using up to 14 days of
      data for each person with occasions (Level 1, N = 2879 days) nested within people
      (Level 2, N = 218 people; 51.4% male). Between-persons (Level 2) effects were
      gender, relationship status, person means of alcohol use, and alcohol-sex
      expectancies for sexual affect and sexual drive. Within-person (Level 1) effects
      were weekend days, number of drinks consumed, and the interaction between drinks
      consumed and alcohol-sex expectancies. Independent of average alcohol use,
      consuming more drinks on a given day was associated with a greater likelihood of
      oral sex and with experiencing more positive consequences of sex that day.
      Significant Alcohol Use x Alcohol-Sex Expectancies interactions were found for
      oral sex and total sex behaviors, indicating that individuals with more positive
      expectancies were more likely to have sex after drinking. The negative
      association between drinks and condom use was at a trend level of significance.
      Results support the potential for promoting sexual health by focusing on cross
      behavior expectancies among late adolescents.

PMID- 19769433
TI  - Evidence for a putative biomarker for substance dependence.
AB  - Electrodermal response modulation (ERM) reflects the reduction in skin
      conductance response to an aversive stimulus that is temporally predictable
      relative to when it is unpredictable. Poor ERM is associated with substance
      dependence (SD). It was hypothesized that ERM is a putative biomarker for SD
      rather than for externalizing disorders generally. Participants included 83
      controls (no SD, antisocial personality disorder [PD] or borderline PD), 52
      participants with SD only (SD and no PD), 12 with PD only (antisocial and/or
      borderline PD and no SD), and 35 comorbid (having SD and PD). Diagnoses at
      definite and probable certainty levels were used and were determined by
      semistructured clinical interviews. ERM was calculated from skin conductance
      responses to predictable and unpredictable 2-s 110-dB white noise blasts. As
      expected, the SD-only and comorbid groups had significantly lower ERM scores than
      the control group, which did not differ significantly from the PD-only group.
      Results provide preliminary evidence that ERM is a putative biomarker for SD.
      Future research should examine cognitive correlates of ERM in an effort to
      understand why it relates to SD.

PMID- 19769432
TI  - Longitudinal association between frequency of substance use and quality of life
      among adolescents receiving a brief outpatient intervention.
AB  - Recognition of the broad consequences of adolescent substance abuse has led to
      increased emphasis on balancing traditional measures of treatment effectiveness,
      such as frequency of substance use, with measures of patient functioning and
      quality of life (QOL). This study evaluated the longitudinal association between
      frequency of use and QOL among adolescent substance abusers receiving a brief
      outpatient intervention. Participants were 106 adolescents, aged 13 to 21 years,
      who met criteria for substance abuse or dependence and completed 4 assessments
      over a 12 month period. Results of a parallel-process latent growth curve model
      indicated a moderate longitudinal association, such that reduced frequency of use
      was associated with QOL improvement. Elaboration of the temporal ordering of this
      association via a cross-lagged panel model revealed that frequency of substance
      use predicted subsequent QOL, but that QOL did not predict subsequent frequency
      of use. Implications pertaining to the assessment of comprehensive outcomes and
      the setting of treatment expectations are discussed.

PMID- 19769434
TI  - Caffeine expectancy: instrument development in the Rasch measurement framework.
AB  - Although caffeine is the most widely consumed psychoactive drug in the world, the
      mechanisms associated with consumption are not well understood. Nonetheless,
      outcome expectancies for caffeine use are thought to underlie caffeine's
      reinforcing properties. To date, however, there is no available, sufficient
      measure by which to assess caffeine expectancy. Therefore, the current study
      sought to develop such a measure employing Rasch measurement models. Unlike
      traditional measurement development techniques, Rasch analyses afford dynamic and
      interactive control of the analysis process and generate helpful information to
      guide instrument construction. A 5-stage developmental process is described,
      ultimately yielding a 37-item Caffeine Expectancy Questionnaire (CEQ) comprised
      of 4 factors representing "withdrawal symptoms," "positive effects," "acute
      negative effects," and "mood effects." Initial evaluation of the CEQ yielded
      sufficient evidence for various aspects of validity. Although additional research
      with more heterogeneous samples is required to further assess the measure's
      reliability and validity, the CEQ demonstrates potential with regard to its
      utility in experimental laboratory research and clinical application.

PMID- 19769435
TI  - The Gambling Craving Scale: Psychometric validation and behavioral outcomes.
AB  - Although craving is an important feature of problem gambling, there is a paucity
      of research investigating craving to gamble. A major stumbling block for craving
      research in gambling has been the lack of a methodologically sound,
      multidimensional measure of gambling-related craving. This article reports the
      development of the Gambling Craving Scale (GACS). In Study 1 (N = 220), a factor
      analysis revealed the emergence of a 9-item scale with 3 factors: Anticipation,
      Desire, and Relief. An important finding was that the GACS predicted problem
      gambling severity, depression, and positive and negative affect. In Study 2 (N =
      145), the factor structure of the GACS was confirmed using a community sample of
      gamblers. In Study 3 (N = 46), GACS scores significantly predicted persistence at
      play on a virtual slot machine in the face of continued loss. Specifically, the
      more participants craved to gamble, the longer they engaged in play. The
      implications of craving for the development and maintenance of problem gambling
      severity are discussed.

PMID- 19769436
TI  - Gambling problem symptom patterns and stability across individual and timeframe.
AB  - Few studies investigate gambling problems at the symptom level; even fewer
      investigate how symptom patterns change throughout the course of a gambling
      disorder. The current study utilized the National Epidemiological Survey on
      Alcohol and Related Conditions (NESARC; Grant et al., 2004) to investigate how
      the specific symptoms of disordered gambling relate to its severity and course.
      Results demonstrated that symptom patterns and stability changed as the number of
      symptoms endorsed increased. Symptom patterns varied considerably from prior to
      past year (PPY) to past year (PY) timeframes. Certain symptoms were more stable
      than others and held predictive value as markers of emerging pathological
      gambling (PG). In particular, gambling to escape problems was one of the most
      stable symptoms and also predictive of progression to PG; reliance on others to
      support gambling was predictive of progression to PG among participants at-risk
      for PG. The differential diagnostic value of various reported symptoms, as well
      as their lack of stability, has implications for both researchers and clinicians.

PMID- 19769437
TI  - Alcohol primes, expectancies, and the working self-concept.
AB  - Previous research has shown that alcohol consumption can lead to momentary
      changes in the self-concept (e.g., Steele & Josephs, 1990). In two studies (n =
      150), we examined whether the implicit activation of alcohol expectancies (i.e.,
      sociability-related expectancies) would also lead to changes in self-perception.
      To test this idea, participants first completed a measure of sociability-related
      alcohol expectancies. In a subsequent laboratory session, participants were
      exposed to either alcohol-related primes (i.e., pictures or words associated with
      alcohol) or neutral primes. After the priming task, participants completed an
      ostensibly unrelated self-concept survey that contained words related to
      sociability (e.g., "outgoing") and nonsociability related words (e.g., "clever").
      For both studies, results revealed that sociability-related alcohol expectancies
      were positively associated with sociability-related self-concept ratings for
      participants exposed to alcohol primes, but not for participants exposed to the
      neutral primes. Implications for the role implicit self-concept activation may
      have on drinking behaviors are discussed.

PMID- 19769438
TI  - Gender-specific normative perceptions of alcohol-related protective behavioral
      strategies.
AB  - The present research aimed (a) to determine whether students underestimate gender
      specific descriptive normative perceptions for protective behavioral strategies;
      (b) to evaluate the relationships among perceived gender-specific descriptive and
      injunctive drinking norms and perceived gender-specific descriptive norms for
      protective behavioral strategies; and (c) to examine whether normative
      perceptions for protective behavioral strategies relate to use of these
      strategies when controlling for relevant drinking behavior factors (i.e., alcohol
      consumption, negative consequences, and attitude toward drinking behavior) and
      social norms factors (i.e., perceived descriptive and injunctive norms). Students
      (N = 666; 56.6% men) completed measures assessing drinking behavior and attitudes
      toward drinking, perceived descriptive and injunctive norms, perceived protective
      behavioral strategies, and protective behavioral strategies. Findings
      demonstrated that students consistently underestimated the use of strategies for
      the typical male student, whereas results were less consistent for the typical
      female student. In addition, results indicated that same-sex normative
      perceptions for protective behavioral strategies were associated with personal
      use of these strategies, even when controlling for relevant drinking behavior and
      social norms factors. Results stress the importance of evaluating factors that
      are associated with use of protective behavioral strategies. Implications for
      social norms preventative interventions are discussed.

PMID- 19769439
TI  - Depression moderates smoking behavior in response to a sad mood induction.
AB  - Stress and anxiety have been shown to increase smoking motivation. There is
      limited experimental data on depressed or sad mood and smoking. This study
      investigated the effects of two induced moods on smoking behavior. Depression
      scores were examined as a potential moderator and mood changes were tested as a
      potential mediator. Smokers (N = 121) were randomly assigned to receive either a
      sad induction or a neutral induction via standardized film clips. Among
      participants with higher depression scores, smoking duration and the number of
      cigarette puffs were greater in response to the sad condition. There was also a
      marginal interactive effect on the change in expired air carbon monoxide among
      this subsample; however, no differences in smoking latency or craving were
      observed. Changes in positive mood partially mediated the effect of condition on
      smoking behavior among participants with high depression scores. There was no
      modifying effect of gender or mediating effect of negative mood changes. The
      results provide preliminary support that decreases in positive mood may have a
      greater influence on smoking behavior among depression-prone smokers than less
      psychiatrically vulnerable smokers.

PMID- 19769440
TI  - Interferons and multiple sclerosis: is it plausible that beta-IFN treatment could
      influence the risk of cancer among MS patients?

PMID- 19769441
TI  - Pharmacogenomics in migraine: catching biomarkers for a predictable disease
      control [corrected].

PMID- 19769442
TI  - Myth of evidence-based medicine for bipolar disorder.

PMID- 19769444
TI  - Role of intraspinal steroid application in patients with multiple sclerosis.
AB  - Clinical trials on patients with progressive multiple sclerosis (MS) have shown
      no clear evidence of an effective symptomatic treatment with improving
      disability. Immunomodulatory compounds efficaciously reduce the relapse rate.
      Numerous earlier papers exist on the pros and cons and/or on the efficacy of
      intrathecal administration of differing dosages of various conventional released
      steroids. Furthermore, this treatment approach was nearly abondoned owing to a
      debate on side effects and a missing proven superiority over intravenous systemic
      high dosage steroid administration. However, recent open-label studies in
      progressive MS patients with predominant spinal symptomatology investigated the
      repeated intraspinal application of the sustained-release compound triamcinolone
      acetonide (TCA). A distinct improvement of walking distance and MS scores in the
      short term and stabilization of this beneficial effect after repeat TCA
      application every 6-12 weeks was found. Moreover, patients with a relapse with
      acute onset of painful sensations showed a marked pain improvement after repeated
      TCA application following prior unsuccessful treatment with intravenous steroids.
      The available data from open studies ask for the performance of a randomized
      clinical trial, comparing intravenous with intrathecal steroid administration, to
      confirm the higher efficacy of the more invasive therapy with repeated lumbar
      puncture.

PMID- 19769445
TI  - Angiotensin AT1-receptor blockers and cerebrovascular protection: do they
      actually have a cutting edge over angiotensin-converting enzyme inhibitors?
AB  - First, an update of the vascular systemic and tissue renin-angiotensin
      aldosterone system is provided to explain how it is regulated at the systemic and
      tissue levels, and how many angiotensin peptides and receptors can be modulated
      by the various antihypertensive drugs. Second, experimental data is presented to
      support the hypothesis that antihypertensive drugs that increase angiotensin II
      formation, such as diuretics, AT1-receptor blockers and dihydropyridines, may
      have greater brain anti-ischemic effects than antihypertensive drugs that
      decrease angiotensin II formation, such as beta-blockers and angiotensin
      converting enzyme inhibitors, because they increase activation of angiotensin AT2
      and AT4 receptors. Indeed, these trigger brain anti-ischemic mechanisms by
      favouring cerebral blood flow (angiogenesis and recruitment of pre-existing
      collateral circulation, specifically in the ischemic brain where AT2 receptors
      are overexpressed) or by directly increasing neuronal resistance to anoxia.
      Third, we review most of the large primary and secondary stroke prevention trials
      as well as the ACCESS acute stroke trial in which antihypertensive drugs were
      evaluated. With the exception of the secondary stroke prevention trial PRoFESS,
      most trials support the hypothesis that angiotensin II-increasing drugs confer
      specific blood pressure-independent brain ischemia protection when compared with
      angiotensin II-decreasing drugs or placebo. A careful analysis of the PRoFESS
      trial, however, reveals study design limitations, the main one being that
      diastolic BP (<80 mmHg) in the first month post-stroke may have been too low in
      at least one third of the population with baseline systolic blood pressure less
      than 130 mmHg, because a high dose of telmisartan was given after a very short
      post-stroke delay (median 15 days) without discontinuation of the baseline
      antihypertensive treatment.

PMID- 19769446
TI  - Guillain-Barre syndrome: update on immunobiology and treatment.
AB  - Growing experimental and clinical data have shed light on the pathophysiology of
      Guillain-Barre syndrome (GBS) and have further promoted the development of novel
      therapeutic strategies for the disorder. Elevated titer of antiganglioside
      antibodies is a characteristic of GBS. This may determine the clinical features
      of each case by binding to the sites where a target ganglioside antigen is
      localized. In experimental models of GBS and its variants, complementary
      inhibitory agents may exert neuroprotective efficacy by inhibiting
      antiganglioside antibody-mediated activation of the classical pathway. Complement
      mediated disruption of the voltage-gated sodium channel cluster has been shown to
      be a principal cause of conduction failure in the model of acute motor axonal
      variants of GBS, protected by a complement inhibitor. Anti-GQ1b antibody-mediated
      injury at motor nerve terminals is also protected by complement inhibitors. In
      the future many kinds of drug candidates that inhibit activation of the
      complement system at various stages will be used in models of autoimmune
      neuropathy, in future applied to clinical trials for GBS and its variants.
      Complement-independent blockade of voltage-gated calcium channels or the
      apoptotic mechanism of neurons should also be considered. The pathogenic effect
      of antiganglioside antibody depends upon the local glycolipid environment in the
      nerve membrane as well as the antibody specificity.

PMID- 19769447
TI  - Acute disseminated encephalomyelitis: postinfectious, postimmunization and
      variant forms.
AB  - Acute disseminated encephalomyelitis is not an uncommon disorder and affects both
      children and adults, being more frequent in the younger group. It is said to
      constitute one third of all encephalidities and usually follows in the wake of a
      banal viral infection, but may occur after immunizations and as a complication of
      diseases affecting the cerebral endothelial cells. There is no specific
      diagnostic test but a good clinical history, attention to clinical findings along
      with MRI scan often help to make the diagnosis. Treatment with high dose steroids
      clearly helps as do immunosuppressives and plasma exchange. Whilst the prognosis
      is generally good, some series have shown 20% mortality, often with high
      morbidity.

PMID- 19769448
TI  - Plasmapheresis for neurological disorders.
AB  - Apheresis is a general term that describes removal of abnormal blood constituents
      by extracorporeal blood purification methods. To date, therapeutic plasma
      exchange (PE) is the most common apheresis procedure. Here, plasma is separated
      from corpuscular blood constituents and replaced with a substitution fluid. In
      contrast to immunoadsorption, PE is a nonspecific treatment modality with
      elimination of the entire plasma. The therapeutic effect is based on the removal
      of circulating, pathogenic immune factors including autoantibodies. Currently, PE
      is used for treatment of several immune-mediated neurological disorders. While
      first experiences relate to acute life-threatening conditions, such as treatment
      of Guillain-Barre syndrome or myasthenic crisis, therapeutic success was also
      shown in chronic diseases where immunosuppressive therapy is often required for
      long-term management. PE has been applied successfully in chronic inflammatory
      demyelinating polyneuropathy, paraproteinemic polyneuropathy, stiff person
      syndrome, and may also be tried in several diseases of paraneoplastic origin. In
      recent years, PE was also established as an escalation therapy for steroid
      unresponsive relapses of multiple sclerosis, and thus has gained more widespread
      attention. Adding to its increasing application in clinical practice, the
      procedure is usually well tolerated. Possible adverse reactions mainly relate to
      vascular access, the use of replacement fluids and the need for anticoagulation.

PMID- 19769449
TI  - Multiple sclerosis lesions: insights from imaging techniques.
AB  - The hallmark of multiple sclerosis (MS) pathology is the presence of inflammatory
      demyelinated lesions distributed throughout the CNS. Along with more diffuse
      tissue abnormalities, it is considered one of the major determinants of
      neurological deficit in MS. Conventional MRI has contributed to improve our
      understanding of MS pathology and has provided objective and reliable measures to
      monitor the effect of treatments. Advanced MRI techniques have offered the
      opportunity to quantify pathological changes in lesions, as well as in normal
      appearing brain tissue and to characterize their dynamics. This review will
      discuss the characteristics and development of MS lesions and the contribution of
      conventional and quantitative MRI techniques to understanding pathological
      changes associated with them.

PMID- 19769450
TI  - Post-traumatic headache.
AB  - Post-traumatic headache (PTH) is a very controversial disorder, particularly when
      it comes to chronic PTH following mild closed head injury and headache attributed
      to whiplash injury. Nevertheless, mild traumatic brain injury is very common in
      Western societies, affecting approximately 1.8 million individuals in the USA.
      Between 30 and 90% of patients develop PTH. Generally, this headache resolves
      within the first 3 weeks after the accident without any specific therapy or long
      term complications but in a minority of patients chronic PTH develops and can be
      associated with serious neurological and neuropsychological deficits. Sufficient
      psychological or neurobiological markers for PTH do not exist, thus treatment can
      be very challenging and should always be multidisciplinary, even in the early
      stages of disease, to make every reasonable effort in preventing the development
      of chronic pain.

PMID- 19769451
TI  - Misdiagnosis of hemicrania continua.
AB  - Hemicrania continua (HC) is a primary headache disorder that is characterized by
      a continuous unilateral headache of moderate severity, exacerbations of severe
      pain, and complete responsiveness to indomethacin. Misdiagnosis of HC is probably
      common in general neurology settings and other clinical specialties. This paper
      is an attempt to bridge the gap between the correct and misdiagnosis of this
      disorder. HC was once thought to be a rare headache disorder, but is, in fact, an
      under-recognized headache syndrome. HC can be of continuous or remitting form.
      Variants such as HC with aura have been described and secondary cases may occur.
      Indomethacin is the best treatment, although HC could respond to other NSAIDs,
      such as the selective COX-2 inhibitors.

PMID- 19769452
TI  - Adverse effects of medications commonly used in the treatment of migraine.
AB  - The classes of medications for migraine treatment are numerous and include
      ergots, triptans, NSAIDs, antidepressants, anti-epilepsy drugs, antihypertensives
      and natural supplements. Physicians need to be aware not only of medication
      efficacy but also of tolerability and safety. Side effects of these drugs can
      sometimes be beneficial, as migraineurs frequently have comorbid conditions. For
      example, those with insomnia can benefit from use of a tricyclic antidepressant
      that is effective in preventing migraine. However, these same coexistent
      conditions can be worsened by migraine medication or be contraindicated and
      multiple medications prescribed for several conditions can result in drug-drug
      interactions. This article reviews adverse events associated with migraine and
      medications, and their implications in clinical treatment.

PMID- 19769453
TI  - Homocysteine, folate and vitamin B12 in neuropsychiatric diseases: review and
      treatment recommendations.
AB  - In Europe, neuropsychiatric diseases currently make up approximately a third of
      the total burden of disease. In 2004, 27% of the overall population was affected
      by at least one of the most frequent neuropsychiatric diseases such as
      Alzheimer's dementia, Parkinson's disease, stroke or depression. The annual costs
      of care exceed those of cancer, cardiovascular conditions and diabetes. In order
      to delay the onset or course of neurodegenerative diseases, the available
      potential should be utilized. As well as improving quality of life of patients
      and relatives, this may reduce the great financial burden caused by
      neurodegenerative disorders. However, the availability of established drugs or
      therapeutic agents is very limited. This paper reviews the state of current
      knowledge as to how homocysteine metabolism is relevant for neurodegenerative and
      other neuropsychiatric diseases, with particular emphasis on the evidence for
      prophylactic and therapeutic strategies. In the European countries, many people
      do not take the recommended daily minimum amount of folate and vitamin B12.
      Deficiency of these vitamins and secondary changes in the concentrations of
      associated metabolites, such as methylmalonic acid and homocysteine, may
      contribute to the onset and progression of neuropsychiatric diseases. This paper
      reviews the evidence regarding whether substitution of folate and vitamin B12 is
      beneficial, for example, in cerebrovascular disease, dementia and depression.

PMID- 19769454
TI  - Prevention of dementia by antihypertensive drugs: how AT1-receptor-blockers and
      dihydropyridines better prevent dementia in hypertensive patients than thiazides
      and ACE-inhibitors.
AB  - Our review of cohort studies and clinical trials evaluating antihypertensive
      drugs in the prevention of cognition decline and all dementia in patients with
      hypertension indicates that two antihypertensive drug classes have greater
      protective effects, independent of blood pressure decrease: dihydropyridine
      calcium-channel blockers as shown in the Syst-Eur trial and angiotensin-AT1
      receptor blockers as found in the MOSES and ONTARGET trials. By contrast,
      diuretics and angiotensin-converting enzyme-inhibitors (ACEIs) prevent dementia
      only in patients with a stroke history, provided they are combined, and prevent
      stroke recurrence. A Japanese cohort study and a small trial in patients already
      suffering from Alzheimer's disease (AD) suggest, however, that the BBB
      penetrating ACEI may slow down cognitive decline. Only cohort studies support the
      hypothesis that diuretics, (especially potassium-sparing diuretics), may decrease
      the risk of AD. beta-blockers worsen cognition decline, or are neutral, according
      to whether or not they cross the BBB. Centrally-acting sympatholytic agent have a
      negative impact on cognition as BBB-penetrating beta-blockers, probably by
      blunting the adrenergic pathways. The AD protective effect of DHP appears related
      to the blockade of neuronal calcium channels. The ambiguous effect of ACEI on
      cognitive decline and dementia prevention may be explained by the fact that brain
      ACE is not specific for angiotensin-I. Brain ACE also catabolizes cognition
      enhancing brain peptides, amyloid peptides and converts toxic Abeta(42) into less
      toxic Abeta(40). Therefore, ACEIs may have short-term cognition-enhancing
      properties and may increase in the long term Abeta(42) brain burden and cognitive
      decline. The clinical relevance of this scenario, mainly observed in animals,
      cannot be excluded in man, since the ACE gene has been associated with AD via the
      human whole genome analysis. To support the hypothesized deleterious effect of
      ACEI on human AD, confirmation that the ACE gene polymorphism DD is associated
      with protection against AD is necessary, since this polymorphism increases ACE
      activity. Independently of their preventive impact on beta-amyloid degenerative
      neuropathological process by overexpressing insulin degrading enzyme which
      catabolyses amyloid, the angiotensin AT1-receptor-blockers may have greater
      cognition protective effects than ACEI (observed in the ONTARGET trial), as they
      share with ACEI cognition-enhancing effects directly linked with a common AT1
      blunting effect. In addition, they increase angiotensin II and IV formation and
      therefore stimulate non-opposed AT2 and AT4 receptors, whose activation in
      cognitive processes is well established.

PMID- 19769456
TI  - Cloning, expression, and characterization of a dithiol glutaredoxin from
      Trypanosoma cruzi.
AB  - Glutaredoxins play an important role in cellular functionality. A putative
      dithiol glutaredoxin is encoded in the genome of Trypanosoma cruzi. We cloned the
      gene and obtained the recombinant protein, which behaved as a typical
      thioltransferase. Activity was variable and dependent on the nature of reducer or
      oxidant agent used, or both. Epimastigote extracts exhibited similar activity,
      suggesting the occurrence of the protein in the parasite. Results support a redox
      scenario in T. cruzi, with glutaredoxin being involved mainly in reduction of
      glutathione disulfide as well as in deglutathionylation of target proteins.

PMID- 19769457
TI  - Physiological and pathophysiological roles of hydrogen sulfide in the
      gastrointestinal tract.
AB  - Like nitric oxide and carbon monoxide, hydrogen sulfide has historically been
      recognized as an industrial pollutant, but in recent years, it has been shown to
      be an important mediator of many physiological processes. Hydrogen sulfide
      contributes to the maintenance of gastrointestinal mucosal defense and repair. It
      also exerts many antiinflammatory effects, including inhibition of leukocyte
      adherence to the vascular endothelium and leukocyte migration to sites of
      inflammation. Conversely, inhibition of endogenous hydrogen sulfide synthesis
      leads to a loss of mucosal integrity and to an increase in mucosal inflammation.
      Hydrogen sulfide therefore appears to have overlapping actions with nitric oxide
      and prostaglandins in terms of modulating mucosal defense and resolution of
      inflammation. Recent evidence suggests that these properties of hydrogen sulfide
      can be exploited in the design of novel therapies for ulcerative and inflammatory
      diseases of the gastrointestinal tract.

PMID- 19769458
TI  - Hydrogen sulfide attenuates hyperhomocysteinemia-induced cardiomyocytic
      endoplasmic reticulum stress in rats.
AB  - The mechanisms responsible for the cardioprotective effect of hydrogen sulfide
      (H(2)S) are unclear. The present study was designed to examine whether H(2)S
      could regulate hyperhomocysteinemia (HHcy)-induced cardiomyocytic endoplasmic
      reticulum (ER) stress. A rat model of HHcy was produced, and H9c2 cells (rat
      embryonic heart-derived cell line) were cultured. The plasma homocysteine was
      measured by using HPLC. Plasma H(2)S concentration and myocardial H(2)S
      production were measured with a sulfide-sensitive electrode. Confocal
      immunofluorescent analysis for cardiomyocytic C/EBP homologous protein (CHOP) was
      performed. Glucose-regulated protein 78 (GRP78), CHOP, and caspase 12 expressions
      by myocardial tissues and cleaved caspase 12 and p-eIF2alpha expressions by H9c2
      cells were detected with Western blotting. The results showed that methionine
      overload induced HHcy, resulting in a marked cardiomyocytic ER stress, whereas
      endogenous production of H(2)S was reduced in rats with HHcy. H(2)S
      supplementation, however, decreased expressions of ER stress-associated proteins,
      including GRP78, CHOP, and caspase 12, by myocardial tissues in vivo. The
      inhibition of endogenous H(2)S production further enhanced cardiomyocytic ER
      stress, but H(2)S supplementation effectively antagonized the H9c2 cell CHOP,
      cleaved caspase 12 and p-eIF2alpha expressions induced by Hcy, thapsigargin, or
      tunicamycin in vitro. The results suggest that H(2)S can attenuate cardiomyocytic
      ER stress in HHcy-induced cardiomyocytic injury.

PMID- 19769459
TI  - The effect of hydrogen sulfide donors on lipopolysaccharide-induced formation of
      inflammatory mediators in macrophages.
AB  - The role of hydrogen sulfide (H(2)S) in inflammation is controversial, with both
      pro- and antiinflammatory effects documented. Many studies have used simple
      sulfide salts as the source of H(2)S, which give a rapid bolus of H(2)S in
      aqueous solutions and thus do not accurately reflect the enzymatic generation of
      H(2)S. We therefore compared the effects of sodium hydrosulfide and a novel slow
      releasing H(2)S donor (GYY4137) on the release of pro- and antiinflammatory
      mediators in lipopolysaccharide (LPS)-treated murine RAW264.7 macrophages. For
      the first time, we show that GYY4137 significantly and concentration-dependently
      inhibits LPS-induced release of proinflammatory mediators such as IL-1beta, IL-6,
      TNF-alpha, nitric oxide (*NO), and PGE(2) but increased the synthesis of the
      antiinflammatory chemokine IL-10 through NF-kappaB/ATF-2/HSP-27-dependent
      pathways. In contrast, NaHS elicited a biphasic effect on proinflammatory
      mediators and, at high concentrations, increased the synthesis of IL-1beta, IL-6,
      NO, PGE(2) and TNF-alpha. This study clearly shows that the effects of H(2)S on
      the inflammatory process are complex and dependent not only on H(2)S
      concentration but also on the rate of H(2)S generation. This study may also
      explain some of the apparent discrepancies in the literature regarding the pro-
      versus antiinflammatory role of H(2)S.

PMID- 19769460
TI  - Regulation of selenoproteins and methionine sulfoxide reductases A and B1 by age,
      calorie restriction, and dietary selenium in mice.
AB  - Methionine residues are susceptible to oxidation, but this damage may be reversed
      by methionine sulfoxide reductases MsrA and MsrB. Mammals contain one MsrA and
      three MsrBs, including a selenoprotein MsrB1. Here, we show that MsrB1 is the
      major methionine sulfoxide reductase in liver of mice and it is among the
      proteins that are most easily regulated by dietary selenium. MsrB1, but not MsrA
      activities, were reduced with age, and the selenium regulation of MsrB1 was
      preserved in the aging liver, suggesting that MsrB1 could account for the
      impaired methionine sulfoxide reduction in aging animals. We also examined
      regulation of Msr and selenoprotein expression by a combination of dietary
      selenium and calorie restriction and found that, under calorie restriction
      conditions, selenium regulation was preserved. In addition, mice overexpressing a
      mutant form of selenocysteine tRNA reduced MsrB1 activity to the level observed
      in selenium deficiency, whereas MsrA activity was elevated in these animals.
      Finally, we show that selenium regulation in inbred mouse strains is preserved in
      an outbred aging model. Taken together, these findings better define dietary
      regulation of methionine sulfoxide reduction and selenoprotein expression in mice
      with regard to age, calorie restriction, dietary Se, and a combination of these
      factors.

PMID- 19769461
TI  - Selenoproteins and protection against oxidative stress: selenoprotein N as a
      novel player at the crossroads of redox signaling and calcium homeostasis.
AB  - Healthy cells continually produce low levels of reactive oxygen species (ROS),
      which are buffered by multiple antioxidant systems. Imbalance between ROS
      production and elimination results in oxidative stress, which has been implicated
      in aging and in numerous human diseases, including cancer and diabetes.
      Selenoproteins are a family of proteins that contain the amino acid
      selenocysteine, encoded by an in-frame UGA. Those selenoproteins whose function
      is identified are catalytically active in redox processes, representing one of
      the main enzymatic antioxidant systems and important mediators of the beneficial
      role of selenium in human health. Nevertheless, the function of most
      selenoproteins remains unknown; this included Selenoprotein N (SelN), the only
      selenoprotein directly associated with a human genetic disease. Mutations of the
      SelN gene cause SEPN1-related myopathy, a particular early-onset muscle disorder.
      Recent studies have identified SelN as a key protein in cell protection against
      oxidative stress and redox-related calcium homeostasis. Furthermore, an effective
      ex vivo treatment of SelN deficiency has been identified, paving the way to a
      clinical therapy. In this review we discuss the physiological and
      pathophysiological role of SelN and the interest of SEPN1-related myopathy as a
      model paradigm to understand and target therapeutically other selenoproteins
      involved in human health and disease.

PMID- 19769462
TI  - Molecular mechanism for H(2)S-induced activation of K(ATP) channels.
AB  - Hydrogen sulfide (H(2)S) is an endogenous opener of K(ATP) channels in many
      different types of cells. However, the molecular mechanism for an interaction
      between H(2)S and K(ATP) channel proteins remains unclear. The whole-cell patch
      clamp technique and mutagenesis approach were used to examine the effects of
      H(2)S on different K(ATP) channel subunits, rvKir6.1 and rvSUR1, heterologously
      expressed in HEK-293 cells. H(2)S stimulated coexpressed rvKir6.1/rvSUR1 K(ATP)
      channels, but had no effect on K(ATP) currents generated by rvKir6.1 expression
      alone. Intracellularly applied sulfhydryl alkylating agent (N-ethylmaleimide,
      NEM), oxidizing agent (chloramine T, CLT), and a disulfide bond-oxidizing enzyme
      (protein disulfide isomerase) did not alter H(2)S effects on this recombinant
      channels. CLT, but not NEM, inhibited basal rvKir6.1/rvSUR1 currents, and both
      abolished the stimulatory effects of H(2)S on K(ATP) currents, when applied
      extracellularly. After selective cysteine residues (C6S and C26S but not C1051S
      and C1057S) in the extracellular loop of rvSUR1 subunits were point-mutated,
      H(2)S lost its stimulatory effects on rvKir6.1/rvSUR1 currents. Our results
      demonstrate that H(2)S interacts with Cys6 and Cys26 residues of the
      extracellular N terminal of rvSUR1 subunit of K(ATP) channel complex. Direct
      chemical modification of rvSUR1 subunit protein constitutes a molecular mechanism
      for the activation of K(ATP) channels by H(2)S.

PMID- 19769463
TI  - Delineating the role of glutathione peroxidase 4 in protecting cells against
      lipid hydroperoxide damage and in Alzheimer's disease.
AB  - Numerous studies characterizing the function of glutathione peroxidase 4 (GPx4)
      have demonstrated that this selenoenzyme is protective against oxidative stress.
      Herein, we characterized the function of this protein by targeting GPx4
      downregulation using RNA interference. Partial knockdown of GPx4 levels resulted
      in growth retardation and morphological changes. Surprisingly, GPx4 knockdown
      cells showed virtually unchanged levels of intracellular ROS, yet highly
      increased levels of oxidized lipid by-products. GPx1, another glutathione
      peroxidase and a major cellular peroxide scavenging enzyme, did not rescue GPx4
      deficient cells and did not reduce lipid peroxide levels. The data established an
      essential role of GPx4 in protecting cells against lipid hydroperoxide damage,
      yet a limited role as a general antioxidant enzyme. As oxidized lipid
      hydroperoxides are a characteristic of neurodegenerative diseases, we analyzed
      brain tissues of mice suffering from a model of Alzheimer's disease and found
      that oxidized lipid by-products were enriched, and expression of both GPx4 and
      guanine-rich sequence-binding factor, which is known to control GPx4 synthesis,
      was downregulated. Brain tissue from an Alzheimer's diseased human also
      manifested enhanced levels of one of the oxidized lipid by-products, 4
      hydroxynonenal. These data suggest a role of GPx4 in neurodegenerative diseases
      through its function in removal of lipid hydroperoxides.

PMID- 19769465
TI  - Selenium and the selenoprotein thioredoxin reductase in the prevention, treatment
      and diagnostics of cancer.
AB  - Selenium is an essential element that is specifically incorporated as
      selenocystein into selenoproteins. It is a potent modulator of eukaryotic cell
      growth with strictly concentration-dependant effects. Lower concentrations are
      necessary for cell survival and growth, whereas higher concentrations inhibit
      growth and induce cell death. It is well established that selenium has cancer
      preventive effects, and several studies also have shown that it has strong
      anticancer effects with a selective cytotoxicity on malignant drug-resistant
      cells while only exerting marginal effects on normal and benign cells. This
      cancer-specific cytotoxicity is likely explained by high affinity selenium uptake
      dependent on proteins connected to multidrug resistance. One of the most studied
      selenoproteins in cancer is thioredoxin reductase (TrxR) that has important
      functions in neoplastic growth and is an important component of the resistant
      phenotype. Several reports have shown that TrxR is induced in tumor cells and pre
      neoplastic cells, and several commonly used drugs interact with the protein. In
      this review, we summarize the current knowledge of selenium as a potent
      preventive and tumor selective anticancer drug, and we also discuss the potential
      of using the expression and modulation of the selenoprotein TrxR in the
      diagnostics and treatment of cancer.

PMID- 19769464
TI  - The syndrome of inherited partial SBP2 deficiency in humans.
AB  - Selenium (Se) is an essential trace element required for the biosynthesis of
      selenoproteins. Selenocysteine insertion sequence (SECIS) binding protein 2
      (SBP2) represents a key trans-acting factor for the co-translational insertion of
      selenocysteine into selenoproteins. In 2005, we reported the first mutations in
      the SBP2 gene in two families in which the probands presented with transient
      growth retardation associated with abnormal thyroid function tests. Intracellular
      metabolism of thyroid hormone (TH) and availability of the active hormone,
      triiodothyronine, is regulated by three selenoprotein iodothyronine deiodinases
      (Ds). While acquired changes in D activities are common, inherited defects in
      humans were not known. Affected children were either homozygous or compound
      heterozygous for SBP2 mutations. Other selenoproteins, glutathione peroxidase,
      and selenoprotein P were also reduced in affected subjects. Since our initial
      report, another family manifesting a similar phenotype was found to harbor a
      novel SBP2 mutation. In vivo studies of these subjects have explored the effects
      of Se and TH supplementation. In vitro experiments have provided new insights
      into the effect of SBP2 mutations. In this review we discuss the clinical
      presentation of SBP2 mutations, their effect on protein function, consequence for
      selenoproteins, and the clinical course of subjects with SBP2 defects.

PMID- 19769466
TI  - Endogenous production of H2S in the gastrointestinal tract: still in search of a
      physiologic function.
AB  - Hydrogen sulfide (H(2)S) has long been associated with the gastrointestinal
      tract, especially the bacteria-derived H(2)S present in flatus. Along with
      evidence from other organ systems, the finding that gastrointestinal tissues are
      capable of endogenous production of H(2)S has led to the hypothesis that H(2)S is
      an endogenous gaseous signaling molecule. In this review, the criteria of
      gasotransmitters are reexamined, and evidence from the literature regarding H(2)S
      as a gaseous signaling molecule is discussed. H(2)S is produced enzymatically by
      gastrointestinal tissues, but evidence is lacking on whether H(2)S production is
      regulated. H(2)S causes well-defined physiologic effects in gastrointestinal
      tissues, but evidence for a receptor for H(2)S is lacking. H(2)S is inactivated
      through enzymatic oxidation, but evidence is lacking on whether manipulating
      H(2)S oxidation alters endogenous cell signaling. Remaining questions regarding
      the role of H(2)S as a gaseous signaling molecule in the gastrointestinal tract
      suggest that H(2)S currently remains a molecule in search of a physiologic
      function.

PMID- 19769467
TI  - Polyvascular atherosclerotic disease: recognizing the risks and managing the
      syndrome.
AB  - BACKGROUND: Patients with an initial ischemic event secondary to atherosclerosis
      have an increased risk of suffering a recurrent event not only in the same
      vascular territory, but in other territories as well. Patients with polyvascular
      disease, or atherosclerotic disease in more than one vascular territory, have
      worse clinical outcomes than those with disease in a single vascular territory.
      This suggests that atherosclerosis should be treated as a systemic disease with
      appropriately aggressive secondary preventive measures in order to prevent
      recurrent events throughout the arterial tree. OBJECTIVE: To discuss relevant
      findings for the management of patients with polyvascular disease and provide
      guidance to clinicians who may not be aware of how best to manage these patients.
      METHODS: Relevant English-language articles published from 1950 through February
      2009 were identified by searching the Cochrane, MEDLINE, and Ovid databases using
      the terms 'atherosclerosis,' 'atherothrombosis,' 'cerebrovascular disease,'
      'coronary artery disease,' 'cross-risk,' 'management guidelines,' 'peripheral
      arterial disease,' 'polyvascular,' and 'secondary prevention' either singly or in
      combination. FINDINGS AND CONCLUSIONS: According to limited data from patient
      registries, anywhere from 15% to 30% of patients with atherosclerosis present
      with disease in multiple vascular territories and experience significantly
      greater rates of adverse cardiovascular events. Despite these findings, a search
      of the literature reveals a lack of studies comprised of patients with
      polyvascular disease only and very few reports on the results of patients with
      polyvascular disease enrolled in existing secondary prevention studies. Although
      any conclusions are limited by this small number of studies, clinicians typically
      treat only the initially affected territory without consideration of the other
      affected territories and may lack awareness of the overall atherothrombotic
      syndrome. In the future, clinical trials focused specifically on patients with
      polyvascular disease should be conducted in order to increase our knowledge on
      how to manage these patients. Evidence-based clinical practice guidelines are
      also necessary to improve the management of patients with polyvascular disease.

PMID- 19769469
TI  - Qualitative research approach in Traditional Chinese Medicine.

PMID- 19769468
TI  - The health reform moment: peril and possibility in the Obama era.

PMID- 19769470
TI  - Herbal self-medication at primary health care facilities in Trinidad.

PMID- 19769471
TI  - Cerebral blood flow effects of yoga training: preliminary evaluation of 4 cases.
AB  - OBJECTIVES: Experienced practitioners of yoga have been shown to alter brain
      function, but this case series measured cerebral blood flow before and after a 12
      week training program in Iyengar yoga (IY) for naive subjects. METHODS: On the
      first day, each of the 4 subjects listened to the teacher speaking on the history
      and background of the yoga program while they were injected with 250 MBq of
      (99m)Tc-bicisate and received a single photon emission computed tomography scan
      (pre-program baseline). Subjects then had their first IY training and were
      injected and scanned with 925 MBq bicisate while they did their first meditation
      (pre-program meditation). Subjects then underwent a 12-week training program in
      IY and then underwent the same imaging protocol with a postprogram baseline and
      postprogram meditation scan. Baseline and meditation scans, before and after
      training, were compared using paired t tests. RESULTS: There were significant
      decreases (p < 0.05) between the pre- and postprogram baseline scans in the right
      amygdala, dorsal medial cortex, and sensorimotor area. There was a significant
      difference (p < 0.05) in the pre- and postprogram percentage change (i.e.,
      activation) in the right dorsal medial frontal lobe, prefrontal cortex, and right
      sensorimotor cortex. CONCLUSIONS: These initial findings suggest the brain
      experiences a "training effect" after 12 weeks of IY training.

PMID- 19769472
TI  - Pilot study of the effect of ultraviolet light on pain and mood in fibromyalgia
      syndrome.
AB  - BACKGROUND: There is a lack of effective systemic or adequate symptomatic
      treatment for pain associated with fibromyalgia syndrome (FMS). Anecdotes suggest
      ultraviolet (UV) light may be of some benefit. PURPOSE: The purpose of the
      present study was to determine if UV is effective in ameliorating chronic pain in
      persons with FMS. METHODS: Nineteen subjects with FMS were enrolled in a
      controlled trial of UV and non-UV (control) tanning beds for 2 weeks, followed by
      randomization to receive UV or non-UV (control) exposure for 6 additional weeks.
      A follow-up interview was conducted 4 weeks after the last treatment. Pain was
      assessed with an 11-point numerical pain rating (Likert scale), a visual analogue
      pain scale (VAS), and the McGill Pain Questionnaire. Mood variables were also
      assessed. RESULTS: During the initial 2 weeks when subjects received both UV and
      non-UV (control) exposures, the 11-point Likert scale pain score decreased 0.44
      points after exposure to UV from pre-exposure levels (S.E. = .095). Additionally,
      UV exposure resulted in greater positive affect, well-being, relaxation, and
      reduced pain levels when compared to non-UV (control) exposure (Odds Ratio [OR] =
      2.80, p = 0.0059). Following the randomized treatment period, there was slight
      improvement in pain as measured by the McGill Pain Questionnaire in the UV group
      compared to the non-UV (control) group (12.2 versus 14.1; p = 0.049); the other
      pain scales yielded nonsignificant results. Assessment 4 weeks after the last
      treatment showed no significant differences in scores in the adjusted means for
      outcomes. CONCLUSIONS: Results from this pilot study suggest that tanning beds
      may have some potential in reducing pain in persons with FMS.

PMID- 19769473
TI  - Resolution of cavitational osteonecrosis through NeuroModulation Technique, a
      novel form of intention-based therapy: a clinical case study.
AB  - OBJECTIVES: This study evaluated the possibility of using NeuroModulation
      Technique (NMT), a form of intention-based medicine, to induce osteogenesis and
      healing of cavitational osteonecrosis, a common progressive form of ischemic
      disease of the alveolar arch. DESIGN: Eleven (11) adult patients were enrolled
      based on the presence of lesions in the jawbone. Ten (10) subjects underwent NMT
      therapy for up to 10 months, while 1 subject received no treatment. OUTCOME
      MEASURES: A sensitive analysis of bone density in the alveolar processes of
      maxilla and mandible was performed before and after therapy using the U.S. Food
      and Drug Administration-approved Cavitat system of through-transmission
      ultrasonography and computer imaging. RESULTS: All subjects presented between one
      and six cavitational lesions at the first scan, most of which (92%) were
      associated with sites of previous tooth extraction. NMT-treated patients
      demonstrated significant improvement in bone density in 27 of the 34 lesions
      analyzed (79%). The median number of lesions per patient was 4 pretreatment and 0
      post-treatment (p < 0.01). One NMT-treated patient, 1 surgically treated patient,
      and the control subject were also imaged at later time points, showing a durable
      healing of the lesions through NMT comparable to that of surgery, as opposed to
      disease persistence in the untreated control. CONCLUSIONS: NMT therapy provides a
      safe and potentially effective treatment for jawbone osteonecrosis. Preclinical
      placebo-controlled trials are encouraged to investigate in depth the potential of
      NMT for treating inflammatory and degenerative pathologies.

PMID- 19769474
TI  - Do cancer patients with a poor prognosis use complementary and alternative
      medicine more often than others?
AB  - INTRODUCTION: One reason for patients with cancer to use complementary and
      alternative medicine (CAM) is that their cancer cannot be cured by conventional
      therapy. The aim of the present study is to explore whether use of CAM is
      associated with survival prognosis in long-term survivors of cancer. MATERIALS
      AND METHODS: Cancer patients who were alive 5 years or more after diagnosis were
      chosen to participate in the study, one group with less than 20% and another
      group with 40%-60% expected five-year survival at the time of diagnosis. A total
      of 735 patients received a four-page postal questionnaire about CAM use; 397
      questionnaires were returned (response rate = 54%). RESULTS: The results are
      reported at five levels of CAM use. The poor prognosis group reported CAM use
      more often than the better prognosis group; however, only significantly higher at
      CAM level 2 (use of a CAM provider) (p = 0.021) and in use of self-support/CAM
      techniques (p < 0.001). Use of over-the-counter (OTC) dietary supplements and use
      of diet as treatment were not significantly different between the groups.
      DISCUSSION: This study supports the suggestion that use of a CAM therapist and
      use of self-support/CAM techniques might be associated with less hope of cure
      given by the physician.

PMID- 19769475
TI  - Mindful exercise, quality of life, and survival: a mindfulness-based exercise
      program for women with breast cancer.
AB  - BACKGROUND: The purpose of this article is to describe the rationale and protocol
      for a pilot study in women with breast cancer that integrates the two
      complementary therapies of mindfulness and exercise. DESIGN: A sample of 30 women
      diagnosed with breast cancer within the previous 12 months who have completed
      initial treatment for their disease will be recruited from oncology physicians'
      offices. The pilot will be a pre-post design, and the study will occur within a
      hospital counseling center for 2 h one day/week for 8 weeks. Participants will
      complete pre-and post-questionnaires on anxiety, depression, quality of life, and
      the post-traumatic stress disorder (PTSD) checklist. Patients will receive
      audiotapes and pedometers and will keep detailed logs of their weekly homework
      assignments. OUTCOME: Appropriate statistical analyses will be carried out to
      arrive at data-driven results. If results show significant benefit for the
      participants, the program will be revised as needed for improvement. DIRECTIONS:
      Future directions will be based on findings of the proposed pilot, which will
      dictate how to proceed after completion of the pilot study. A future goal, if
      preliminary findings and a replication study are encouraging, will be the
      development of a Mindfulness-based Exercise Program Manual for dissemination and
      use by researchers and clinicians to help empower patients with cancer.

PMID- 19769476
TI  - Application of Delphi technique in identification of appropriate screening
      questions for chronic low back pain from traditional Chinese medicine experts'
      opinions.
AB  - OBJECTIVE: The goal of the present study was to obtain a standard list of
      traditional Chinese medicine (TCM) symptoms and signs for screening chronic low
      back pain (cLBP) from a group of experts and to assess agreement and consistency
      among their opinions on the items of a questionnaire. DESIGN, SETTINGS, AND
      SUBJECTS: The study design involved three rounds of modified Delphi technique,
      and it was carried out by 13 experts in orthopedics, massage, and acupuncture
      working in four hospitals affiliated with Yunnan University of Traditional
      Chinese Medicine, China. OUTCOME MEASURES: The outcome was measured on the 5
      score Likert-scale self-administered checklists. RESULTS: A review of eight
      textbooks identified 12 pain characteristics, 11 associated factors, and 25
      physical and tongue diagnostic expressions as important factors in the TCM
      diagnosis of cLBP. These 48 diagnostic characteristics were rated by 13 experts
      as "not important" to "very important" on a scale of 1-5. After three rounds of
      rating, 13 characteristics were eliminated from the list, with the final numbers
      for each group being 8, 11, and 16, respectively. Seven items based on Western
      medicine were also added by the experts. The intra-class correlation (ICC)
      coefficient for agreement among the experts was 0.2 at the end. Intra-rater,
      between rounds, consecutive pair-wise median kappa values were 0.53 and 0.66.
      Analysis of variance using items appearing in all three rounds revealed
      significant effects of expert and group of symptoms and signs (p < 0.001) and
      nonsignificant differences among scores of the same expert in the three rounds (p
      = 0.97). Mean score of physical and tongue expressions was significantly (p <
      0.001) lower than that of all other groups of symptoms and signs. CONCLUSIONS:
      Modern TCM experts have de-emphasized the items on physical and tongue
      expressions and have adopted instead those from Western medicine. Intra-expert
      agreement across items was low, and each expert tended to stick to her/his
      original opinions.

PMID- 19769477
TI  - Effects of music and essential oil inhalation on cardiac autonomic balance in
      healthy individuals.
AB  - OBJECTIVE: The purpose of the present study was to investigate the effect of
      listening to soft music or inhaling Citrus bergamia aroma on autonomic nervous
      system activity in young healthy individuals. STUDY DESIGN, LOCATION, AND
      SUBJECTS: This single-institution study was an open-label randomized controlled
      trial carried out on 114 healthy undergraduate students at a university located
      in south Taiwan. INTERVENTION: Participants were randomly allocated to one of
      four study groups including (1) a music group, (2) an aroma group, (3) a combined
      music and aroma group, and (4) a control group. Participants in the music group
      were asked to listen to preselected soft music for 15 minutes, and those in the
      aroma group were asked to inhale Citrus bergamia essential oil vapor generated
      from an ultrasonic atomizer for 15 minutes. OUTCOME MEASURE: The outcome measure
      involved heart rate variability (HRV) indices measured before and after the
      intervention. The low frequency (LF) and high frequency (HF) components of the
      HRV were used to quantify modulation of the sympathetic and parasympathetic
      branches of the autonomic nervous system. RESULTS: The percentage changes of
      normalized LF (p = 0.003), normalized HF (p = 0.001), and the ratio of LF to HF
      (p < 0.001) were significantly different among the four groups. Tukey's post hoc
      analysis revealed that the percentage change of normalized LF and HF were
      significantly different between the control group and the music group. For the
      percentage change of the ratio of LF to HF, the negative change in the music
      group, the aroma group, and the combined group was significantly different from
      that of the increase in the control group. In addition, no significant
      differences were found in the percentage changes in systolic blood pressure,
      diastolic blood pressure, and mean heart rate in the four groups. CONCLUSIONS:
      Listening to soft music and inhaling Citrus bergamia essential oil was found to
      be an effective method of relaxation, as indicated by a shift of the autonomic
      balance toward parasympathetic activity in young healthy individuals.

PMID- 19769478
TI  - Evaluation of medicinal plants as part of Tibetan medicine prospective
      observational study in Sikkim and Nepal.
AB  - OBJECTIVE: Medicinal plants are the primary ingredients of Tibetan medicinal
      formulae. The aim of the present study was to evaluate the spectrum of medical
      complaints treated by a Tibetan doctor in Sikkim and Nepal, and to determine
      which plants the doctor used most frequently to treat these complaints. DESIGN:
      Two prospective observational studies were carried out at two locations (Sikkim
      and Nepal). Patients who visited the participating Tibetan doctor were included
      consecutively. Medical symptoms, Tibetan syndrome diagnoses, and treatments were
      documented. The most frequently used plants were identified retrospectively.
      RESULTS: A total of 238 patients were included (Sikkim: n = 135, 62.2% women,
      mean age 33.9 3.4 years; Nepal: n = 103, 54.4% men, mean age 42.9 2.4 years). The
      most frequent medical complaint was pain (Sikkim: 46% of patients; Nepal: 51% of
      patients). The most frequent Tibetan syndrome diagnosis was Bad-kan in Sikkim
      (20.7% of patients; a cold disorder affecting the lower body) and a combination
      of Bad-kan and mKhris-pa in Nepal (28.2%; a mixed cold/hot disorder affecting the
      lower and middle body). A total of 71 different Tibetan medicines were
      prescribed, including 138 different plants. Of these 138 plants, 81 typically
      grow at high and medium altitudes, and 57 grow in tropical and subtropical areas.
      Nevertheless, most (93%) of the prescribed formulae contained high-altitude
      plants. CONCLUSIONS: For the first time, information on medical complaints and
      treatments has been evaluated systematically for patients receiving treatment
      from a Tibetan doctor. These data provide a good foundation for further research
      on Tibetan medicine. Further studies should go a step farther and include follow
      up data and information about the effectiveness and safety of Tibetan medicines.

PMID- 19769479
TI  - Self-reported quality of life in complementary and alternative medicine treatment
      of chronic rhinosinusitis among African Americans: a preliminary, open-label
      pilot study.
AB  - OBJECTIVE: The southern U.S. region has among the highest incidence of chronic
      rhinosinusitis (CRS). Historically, African Americans in this region have been a
      difficult to reach population for clinical research participation. This study's
      aim was to observe any association between herbal tea consumption and CRS
      symptoms among African Americans. We recount the volunteers self-reporting of
      measurements associated with self-treatment of CRS symptoms. DESIGN: The study
      design was a preliminary, open-label, pilot study. SETTINGS: Volunteers were
      drawn from Morehouse School of Medicine's outpatient clinics, community
      multipurpose senior centers, and churches in Fulton and DeKalb Counties, GA.
      SUBJECTS: One hundred (100) African American volunteers were prescreened, of whom
      55 with a clinical diagnosis of CRS met entrance criteria. INTERVENTION:
      Volunteers self-administered Breathe Easy herbal tea for a duration of 6 weeks.
      OUTCOME MEASURES: The Chronic Sinusitis Survey (CSS) scale was administered to
      assess sinus health at baseline and term and overall quality of life was assessed
      using the Short Form-36 (SF-36) index. RESULTS: Of the 55 volunteers who met
      entrance criteria, 41 completed the study; groups were q.i.d. (n = 27), t.i.d. (n
      = 4), b.i.d. (n = 5), and noncompliant (n = 5). For the q.i.d. group (n = 27),
      there was a significant increase in the CSS symptom score (difference in means
      22.0 points; p = 0.020) and CSS total score (11.1 points; p = 0.020). Overall
      health status (SF-36) reported at baseline was 35% very good; 34% good; and 17%
      fair. After 6-weeks, the q.i.d. group showed a significant change to 44% good and
      45% very good (p = 0.001). CONCLUSIONS: This preliminary pilot study suggests
      that q.i.d. self-administration of Breathe Easy was associated with improved
      volunteers' sinus health status (e.g., ability to fall sleep). Our results
      suggest that this herbal tea may contribute as a complementary therapy for
      management of CRS among African Americans. To further assess efficacy and
      applicability to other populations, randomized controlled trials in larger
      populations are warranted.

PMID- 19769480
TI  - A pilot observational study to assess the safety and efficacy of Menoprogen for
      the management of menopausal symptoms in Chinese women.
AB  - OBJECTIVE: Over the past 5 years, the interest in alternative therapies for
      menopause has increased dramatically due to the findings of the Women's Health
      Initiative (U.S. National Institutes of Health). Menoprogen, a traditional
      Chinese medicine formulation is an herbal remedy that has been used in China for
      the management of menopause-related symptoms. An observational pilot study was
      performed to assess the effects of Menoprogen in the management of menopausal
      symptoms in perimenopausal and postmenopausal women. DESIGN, SUBJECTS, AND
      SETTING: A multicenter prospective study was conducted at four clinical centers
      in China. Female subjects were eligible if they had menopausal diagnosis for at
      least 3 months and wished to use an alternative to hormone replacement therapy
      (HRT). INTERVENTION: Subjects received two capsules of Menoprogen (a combination
      product containing 0.2 g extracts of five herbs per capsule) orally, twice daily.
      MAIN OUTCOME MEASURES: The primary outcome measured was an improvement of
      Kupperman Menopausal Index (KMI) from baseline. Secondary outcomes measured
      included hormone levels and the status of the endometrial and vaginal cytology
      after completion of treatment. RESULTS: After treatment with Menoprogen, a
      significant reduction in the KMI was observed (mean of paired difference = 
      14.875; p < 0.01) as compared with baseline. Endogenous estrogen levels were
      significantly increased with Menoprogen (mean of paired difference = -3.145; p <
      0.01). Progesterone levels increased with Menoprogen (mean of paired difference =
      -10.003; p < 0.01). Both follicle stimulating hormone (FSH) and luteinizing
      hormone (LH) levels showed significant before-and-after treatment difference
      (mean of paired difference = 6.125 mIU/mL for FSH and 4.938 mIU/mL for LH; p <
      0.01). No significant endometrial hyperplasia was observed post-treatment with
      Menoprogen. Most of the postmenopausal women exhibited a vaginal cell
      proliferation degree of 2-3, suggesting a possible estrogenic effect.
      CONCLUSIONS: The present pilot study found that Menoprogen reduced symptoms
      associated with perimenopausal and postmenopausal complaints. Therefore, the
      rationale for a randomized, placebo-controlled clinical trial is supported.

PMID- 19769481
TI  - Severity of Yin deficiency syndrome and autonomic nervous system function in
      cancer patients.
AB  - OBJECTIVE: To evaluate the distribution of symptoms related to Yin deficiency
      syndrome (YDS), and to analyze the relationship between the severity of YDS and
      the function of the autonomic nervous system (ANS) in cancer patients. SETTING:
      Outpatient clinic in a teaching hospital in central Taiwan. SUBJECTS: Eighty (80)
      patients had been diagnosed with cancer by pathologic and clinical findings.
      METHOD: The severity of YDS in each subject was evaluated by a questionnaire
      consisting of 12 items concerning symptoms and signs related to YDS, scored from
      1 to 4 points. OUTCOME MEASURES: The total score for all 12 items represented the
      severity of YDS. ANS function in each subject was evaluated by measuring heart
      rate variability (HRV), including time-frequency analysis. We coded the collected
      questionnaire material and performed statistical analysis (description analysis,
      ANOVA, and Pearson's correlation coefficients) using SPSS v.12.0 software.
      RESULTS: The highest total YDS score was 36 points and the lowest was 10 points.
      The 3 most common YDS signs were dry mouth (58.8%), sleeplessness with annoyance
      (56.3%), and flush over face in the afternoon (22.5%). The total YDS scores had a
      significantly positive correlation with heart rate (HR), but had significantly
      negative correlation with the standard deviation of the 5-minute mean R-R
      intervals (SDANN), total HRV power, power in the very low frequency band, and in
      the low frequency band. CONCLUSIONS: The above results suggest that the severity
      of YDS in cancer patients was associated with increased HR and decreased ANS
      activity. There is a possibility that the disturbance of ANS function may
      contribute to the occurrence of YDS in cancer patients.

PMID- 19769482
TI  - Chinese medicinal herbs in relieving perimenopausal depression: a randomized,
      controlled trial.
AB  - OBJECTIVE: To explore the effects of GengNianLe (GNL, also called perimenopausal
      depression relieving formula), a defined formula of Chinese medicinal herbs in
      relieving perimenopausal depression in Chinese women. METHODS: Between September
      2004 and April 2008, 47 Chinese women were randomized into a GNL group (n = 21)
      and a control group which received tibolone (n = 26) using a randomization chart.
      Depression was rated with the 24-item Hamilton Depression Scale (HAMD). The serum
      levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), and
      estradiol (E(2)) were detected before and after the treatment. RESULTS: After 12
      weeks of treatment, HAMD scores in both groups decreased significantly (p < 0.05)
      with no significant difference between the groups (p > 0.05). The levels of FSH
      decreased significantly and the level of E(2) increased significantly in both
      groups, and they changed more in the control group. No side-effect of treatment
      was reported in either group during treatment. CONCLUSIONS: The Chinese medicinal
      formula GNL showed promise in relieving perimenopausal depression and merits
      further study.

PMID- 19769483
TI  - Divergent effects of alpha-tocopherol and vitamin C on the generation of
      dysfunctional HDL associated with diabetes and the Hp 2-2 genotype.
AB  - The haptoglobin (Hp) 2-2 genotype is associated with increased risk of
      cardiovascular disease (CVD) in diabetes (DM). We recently proposed this
      increased risk arises from the tethering of redox active hemoglobin (Hb) to high
      density lipoprotein (HDL), thereby resulting in oxidative modification of HDL.
      Clinical trials have demonstrated that vitamin E (alpha-tocopherol) decreases
      while vitamin C increases CVD in Hp 2-2 DM individuals. We sought to test the
      hypothesis that the interaction of alpha-tocopherol or vitamin C on CVD in Hp 2-2
      DM was due to their divergent effects on HDL oxidation and function. Vitamin C
      significantly increased while alpha-tocopherol completely blocked oxidation
      mediated by glycosylated Hb-Hp 2-2. Vitamin C had no benefit while alpha
      tocopherol completely restored HDL function in Hp 2-2 DM mice. Co-administration
      of vitamin C mitigated the protective effects of alpha-tocopherol on HDL. There
      exists a pharmacogenomic interaction between vitamin C and alpha-tocopherol and
      the Hp 2-2 genotype on HDL function and structure. Choosing the correct
      antioxidant in the correct subset of patients may be critical in order to
      demonstrate benefit from antioxidant therapy.

PMID- 19769484
TI  - Novel insights into hydrogen sulfide--mediated cytoprotection.
AB  - Hydrogen sulfide (H(2)S) is a colorless, water soluble, flammable gas that has
      the characteristic smell of rotten eggs. Like other members of the
      gasotransmitter family (nitric oxide and carbon monoxide), H(2)S has
      traditionally been considered to be a highly toxic gas and environmental hazard.
      However, much like for nitric oxide and carbon monoxide, the initial negative
      perception of H(2)S has evolved with the discovery that H(2)S is produced
      enzymatically in mammals under normal conditions. As a result of this discovery,
      there has been a great deal of work to elucidate the physiological role of H(2)S.
      H(2)S is now recognized to be cytoprotective in various models of cellular
      injury. Specifically, it has been demonstrated that the acute administration of
      H(2)S, either prior to ischemia or at reperfusion, significantly ameliorates in
      vitro or in vivo myocardial and hepatic ischemia-reperfusion injury. These
      studies have also demonstrated a cardioprotective role for endogenous H(2)S. This
      review article summarizes the current body of evidence demonstrating the
      cytoprotective effects of H(2)S with an emphasis on the cardioprotective effects.
      This review also provides a detailed description of the current signaling
      mechanisms shown to be responsible for these cardioprotective actions.

PMID- 19769485
TI  - The neuroprotective functions of selenoprotein M and its role in cytosolic
      calcium regulation.
AB  - Selenoproteins contain the trace element selenium incorporated as selenocysteine,
      the 21st amino acid. Some members of the selenoprotein family, such as the
      glutathione peroxidases, have well-characterized antioxidant activity,
      functioning in enzymatic breakdown of hydroperoxides to protect cells against
      oxidative stress. However, the functions of many of the 25 human selenoproteins,
      including the brain-enriched selenoprotein M, are unknown. We investigated
      selenoprotein M function by manipulating expression in murine hippocampal HT22
      cells, cerebellar astrocyte C8-D1A cells, and primary neuronal cultures.
      Overexpression of the protein resulted in a reduction in reactive oxygen species
      and apoptotic cell death in response to oxidative challenge with hydrogen
      peroxide. In contrast, knock-down of selenoprotein M using shRNA in primary
      neuronal cultures caused apoptotic cell death comparable to levels resulting from
      addition of hydrogen peroxide. Calcium measurements with the indicator cameleon
      demonstrated that overexpression of selenoprotein M decreased calcium influx in
      response to hydrogen peroxide. Additionally, knock-down of selenoprotein M
      expression in cortical cultures caused higher baseline levels of cytosolic
      calcium than in control cells. These results suggest that selenoprotein M may
      have an important role in protecting against oxidative damage in the brain and
      may potentially function in calcium regulation.

PMID- 19769486
TI  - The effect of mesenchymal stromal cells on the osseoinduction of impaction
      grafts.
AB  - Revision total hip replacement has a failure rate of up to 25%. Part of the
      reason for this high failure is the lack of bone stock. In this study, we
      investigated whether mesenchymal stromal cells (MSCs) or osteoprogenitors (OPs)
      contribute to bone formation in impacted allograft or an allograft and
      hydroxyapatite (HA) combination. Eight samples were inserted in the paraspinal
      muscles of six sheep, which were allograft or an HA/allograft mix, seeded with
      autologous MSCs, autologous OPs, or no cells (control), and impacted with a
      clinically relevant force at 3 kN preimplantation. Other groups were HA blocks
      seeded with or without MSCs. Samples were retrieved at 12 weeks. MSCs
      incorporated into allograft, HA/allograft, and HA blocks displayed higher mean
      values of new bone formation compared with the controls, but there was no
      statistical difference between allograft groups. However, in HA/allograft groups,
      significantly more new bone was found with MSCs than without cells (p = 0.046) or
      with OPs (p = 0.028). In the HA blocks, more new bone was found in the MSC group
      than in the HA block without cells (p = 0.028). In conclusion, MSCs used with
      combinations of allograft and HA enhance new bone formation in an ovine ectopic
      site after being subjected to realistic forces that are used during impaction
      grafting.

PMID- 19769487
TI  - Surgical management of cervical degenerative disease: the evidence related to
      indications, impact, and outcome.
AB  - In this special edition of Journal of Neurosurgery: Spine, a series of systematic
      reviews sponsored by the Section on Disorders of the Spine and Peripheral Nerves
      of the American Association of Neurological Surgeons/Congress of Neurological
      Surgeons is presented. This collection of comprehensive reviews summarizes the
      medical evidence related to the surgical management of cervical degenerative disc
      disease. Several of the key conclusions are discussed in this introduction to the
      issue: There is Class II evidence to suggest that the clinical condition remains
      stable when observed over a 3-year period in patients with mild-to-moderate
      cervical spondylotic myelopathy (CSM) and age younger than 75 years. There is
      consistent Class III evidence that the duration of symptoms, and possibly
      advancing age, negatively affect outcome in patients with CSM. There is Class II
      evidence that somatosensory evoked potentials have prognostic value in patients
      with CSM. There is Class I evidence to show that electromyographic abnormalities
      (as well as the presence of radiculopathy) are predictive of the development of
      myelopathy in minimally symptomatic patients with cervical stenosis and spinal
      cord compression. The presence of a low signal on T1-weighted images, high signal
      on T2-weighted images, and the presence of cord atrophy on preoperative MR images
      are indicators of a poor outcome in CSM. There is Class III evidence to show that
      anterior or posterior surgical approaches that effectively decompress the
      cervical canal promote short-term improvements in outcome. However, there appears
      to be a risk of late kyphosis in patients who undergo laminectomy or anterior
      cervical discectomy alone compared with patients in whom decompression is
      combined with fusion. The use of BMP-2 is discouraged for anterior cervical spine
      surgery based on evidence suggesting that the risks outweigh any potential
      benefits. Finally, in patients with symptomatic cervical radiculopathy,
      arthroplasty achieves outcomes that are equivalent to anterior cervical
      decompression and fusion, although evidence for superiority is lacking. Further
      prospective longitudinal data are required to better define the role and timing
      of surgical intervention in CSM and to determine the appropriate use of cervical
      arthroplasty in the management of symptomatic cervical degenerative disc disease.

PMID- 19769488
TI  - Introduction and methodology: guidelines for the surgical management of cervical
      degenerative disease.
AB  - In March 2006, the Joint Section on Disorders of the Spine and Peripheral Nerves
      of the American Association of Neurological Surgeons and Congress of Neurological
      Surgeons compiled an expert group to perform an evidence-based review of the
      clinical literature on management of cervical degenerative spine disease. This
      process culminated in the formation of the Guidelines for the Surgical Management
      of Cervical Degenerative Disease. The purpose of the Guidelines was to address
      questions regarding the therapy, diagnosis, and prognosis of cervical
      degenerative disease using an evidence-based approach. Development of an evidence
      based review and recommendations is a multitiered process. Typical guideline
      development consists of 5 processes: 1) collection and selection of the evidence;
      2) assessment of the quality and strength of the evidence; 3) analysis of the
      evidentiary data; 4) formulation of recommendations; and 5) guideline validation.
      This manuscript details the methodology in compiling the Guidelines for the
      Surgical Management of Cervical Degenerative Disease.

PMID- 19769489
TI  - The natural history of cervical spondylotic myelopathy.
AB  - OBJECT: The objective of this systematic review was to use evidence-based
      medicine to delineate the natural history of cervical spondylotic myelopathy
      (CSM) and identify factors associated with clinical deterioration. METHODS: The
      National Library of Medicine and Cochrane Database were queried using MeSH
      headings and keywords relevant to the natural history of CSM. Abstracts were
      reviewed and studies meeting the inclusion criteria were selected. The guidelines
      group assembled an evidentiary table summarizing the quality of evidence (Classes
      I-III). Disagreements regarding the level of evidence were resolved through an
      expert consensus conference. The group formulated recommendations that contained
      the degree of strength based on the Scottish Intercollegiate Guidelines network.
      Validation was done through peer review by the Joint Guidelines Committee of the
      American Association of Neurological Surgeons and the Congress of Neurological
      Surgeons. RESULTS: The natural history of CSM is mixed: it may manifest as a
      slow, stepwise decline or there may be a long period of quiescence (Class III).
      Long periods of severe stenosis are associated with demyelination and may result
      in necrosis of both gray and white matter. With severe and/or long lasting CSM
      symptoms, the likelihood of improvement with nonoperative measures is low.
      Objectively measurable deterioration is rarely seen acutely in patients younger
      than 75 years of age with mild CSM (modified Japanese Orthopaedic Association
      scale score > 12; Class I). In patients with cervical stenosis without
      myelopathy, the presence of abnormal electromyography findings or the presence of
      clinical radiculopathy is associated with the development of symptomatic CSM in
      this patient population (Class I). CONCLUSIONS: The natural history of CSM is
      variable, which may affect treatment decisions.

PMID- 19769490
TI  - Clinical prognostic indicators of surgical outcome in cervical spondylotic
      myelopathy.
AB  - OBJECT: The objective of this systematic review was to use evidence-based
      medicine to assess whether clinical factors predict surgical outcomes in patients
      undergoing cervical surgery. METHODS: The National Library of Medicine and
      Cochrane Database were queried using MeSH headings and keywords relevant to
      clinical preoperative factors. Abstracts were reviewed, and studies that met the
      inclusion criteria were selected. The guidelines group assembled an evidentiary
      table summarizing the quality of evidence (Classes I-III). Disagreements
      regarding the level of evidence were resolved through an expert consensus
      conference. The group formulated recommendations that contained the degree of
      strength based on the Scottish Intercollegiate Guidelines network. Validation was
      done through peer review by the Joint Guidelines Committee of the American
      Association of Neurological Surgeons/Congress of Neurological Surgeons. RESULTS:
      Preoperative sensory-evoked potentials may aid in providing prognostic
      information in selected patients in whom clinical factors do not provide clear
      guidance (Class II). Age, duration of symptoms, and preoperative neurological
      function may commonly affect outcome (Class III). CONCLUSIONS: Age, duration of
      symptoms, and preoperative neurological function should be discussed with
      patients when surgical intervention for cervical spondylotic myelopathy is
      considered. Preoperative sensory-evoked potentials may be considered for patients
      in whom clinical factors do not provide clear guidance if such information would
      potentially change therapeutic decisions.

PMID- 19769491
TI  - Preoperative patient selection with magnetic resonance imaging, computed
      tomography, and electroencephalography: does the test predict outcome after
      cervical surgery?
AB  - OBJECT: The objective of this systematic review was to use evidence-based
      medicine to assess whether preoperative imaging or electromyography (EMG)
      predicts surgical outcomes in patients undergoing cervical surgery. METHODS: The
      National Library of Medicine and Cochrane Database were queried using MeSH
      headings and keywords relevant to the preoperative imaging and EMG. Abstracts
      were reviewed after which studies meeting inclusion criteria were selected. The
      guidelines group assembled an evidentiary table summarizing the quality of
      evidence (Classes I-III). Disagreements regarding the level of evidence were
      resolved through an expert consensus conference. The group formulated
      recommendations that contained the degree of strength based on the Scottish
      Intercollegiate Guidelines network. Validation was done through peer review by
      the Joint Guidelines Committee of the American Association of Neurological
      Surgeons/Congress of Neurological Surgeons. RESULTS: Preoperative MR imaging and
      CT myelography are successful in confirming clinical radiculopathy (Class II).
      Multilevel T2 hyperintensity, T1 focal hypointensity combined with T2 focal
      hyperintensity, and spinal cord atrophy each convey a poor prognosis (Class III).
      There is conflicting data concerning whether focal T2 hyperintensity or cervical
      stenosis are associated with a worse outcome. Electromyography has mixed utility
      in predicting outcome (Class III). CONCLUSIONS: Magnetic resonance imaging or CT
      myelography are important for preoperative assessment. Magnetic resonance imaging
      may be helpful in assessing prognosis, whereas EMG has mixed utility in assessing
      outcome.

PMID- 19769492
TI  - Cervical surgical techniques for the treatment of cervical spondylotic
      myelopathy.
AB  - OBJECT: The objective of this systematic review was to use evidence-based
      medicine to compare the efficacy of different surgical techniques for the
      treatment of cervical spondylotic myelopathy (CSM). METHODS: The National Library
      of Medicine and Cochrane Database were queried using MeSH headings and keywords
      relevant to anterior and posterior cervical spine surgery and CSM. The guidelines
      group assembled an evidentiary table summarizing the quality of evidence (Classes
      I-III). The group formulated recommendations that contained the degree of
      strength based on the Scottish Intercollegiate Guidelines network. Validation was
      done through peer review by the Joint Guidelines Committee of the American
      Association of Neurological Surgeons/Congress of Neurological Surgeons. RESULTS:
      A variety of techniques have improved functional outcome after surgical treatment
      for CSM, including anterior cervical discectomy with fusion (ACDF), anterior
      cervical corpectomy with fusion (ACCF), laminoplasty, laminectomy, and
      laminectomy with fusion (Class III). Anterior cervical discectomy with fusion and
      ACCF appear to yield similar results in multilevel spine decompression for
      lesions at the disc level. The use of anterior plating allows for equivalent
      fusion rates between these techniques (Class III). If anterior fixation is not
      used, ACCF may provide a higher fusion rate than multilevel ACDF but also a
      higher graft failure rate than multilevel ACDF (Class III). Anterior cervical
      discectomy with fusion, ACCF, laminectomy, laminoplasty, and laminectomy with
      arthrodesis all provide near-term functional improvement for CSM. However,
      laminectomy is associated with late deterioration compared with the other types
      of anterior and posterior surgeries (Class III). CONCLUSIONS: Multiple approaches
      exist with similar near-term improvements; however, laminectomy appears to have a
      late deterioration rate that may need to be considered when appropriate.

PMID- 19769493
TI  - Cervical laminectomy for the treatment of cervical degenerative myelopathy.
AB  - OBJECT: The objective of this systematic review was to use evidence-based
      medicine to examine the efficacy of cervical laminectomy for the treatment of
      cervical spondylotic myelopathy (CSM). METHODS: The National Library of Medicine
      and Cochrane Database were queried using MeSH headings and keywords relevant to
      cervical laminectomy and CSM. Abstracts were reviewed after which studies meeting
      inclusion criteria were selected. The guidelines group assembled an evidentiary
      table summarizing the quality of evidence (Classes I-III). Disagreements
      regarding the level of evidence were resolved through an expert consensus
      conference. The group formulated recommendations that contained the degree of
      strength based on the Scottish Intercollegiate Guidelines network. Validation was
      done through peer review by the Joint Guidelines Committee of the American
      Association of Neurological Surgeons/Congress of Neurological Surgeons. RESULTS:
      Laminectomy has improved functional outcome for symptomatic cervical myelopathy
      (Class III). The limitations of the technique are an increased risk of
      postoperative kyphosis compared to anterior techniques or laminoplasty or
      laminectomy with fusion (Class III). However, the development of kyphosis may not
      necessarily to diminish the clinical outcome (Class III). CONCLUSIONS:
      Laminectomy is an acceptable therapy for near-term functional improvement of CSM
      (Class III). It is associated with development of kyphosis, however.

PMID- 19769494
TI  - Laminectomy and fusion for the treatment of cervical degenerative myelopathy.
AB  - OBJECT: The objective of this systematic review was to use evidence-based
      medicine to examine the efficacy of cervical laminectomy and fusion for the
      treatment of cervical spondylotic myelopathy (CSM). METHODS: The National Library
      of Medicine and Cochrane Database were queried using MeSH headings and keywords
      relevant to cervical laminectomy, fusion, and CSM. Abstracts were reviewed, after
      which studies that met the inclusion criteria were selected. The guidelines group
      assembled an evidentiary table summarizing the quality of evidence (Class I-III).
      Disagreements regarding the level of evidence were resolved through an expert
      consensus conference. The group formulated recommendations which contained the
      degree of strength based on the Scottish Intercollegiate Guidelines network.
      Validation was done through peer-review by the Joint Guidelines Committee of the
      American Association of Neurological Surgeons/Congress of Neurological Surgeons.
      RESULTS: Cervical laminectomy with fusion (arthrodesis) improves functional
      outcome in patients with CSM and ossification of the posterior longitudinal
      ligament (OPLL). Functional improvement is similar to laminectomy or laminoplasty
      for patients with CSM and OPLL. In contrast to laminectomy, cervical laminectomy
      with fusion it is not associated with late deformity (Class III). CONCLUSIONS:
      Laminectomy with fusion (arthrodesis) is an effective strategy to improve
      functional outcome in CSM and OPLL.

PMID- 19769495
TI  - Cervical laminoplasty for the treatment of cervical degenerative myelopathy.
AB  - OBJECT: The objective of this systematic review was to use evidence-based
      medicine to examine the efficacy of cervical laminoplasty in the treatment of
      cervical spondylotic myelopathy (CSM). METHODS: The National Library of Medicine
      and Cochrane Database were queried using MeSH headings and keywords relevant to
      cervical laminoplasty and CSM. Abstracts were reviewed and studies meeting the
      inclusion criteria were selected. The guidelines group assembled an evidentiary
      table summarizing the quality of evidence (Classes I-III). Disagreements
      regarding the level of evidence were resolved through an expert consensus
      conference. The group formulated recommendations that contained the degree of
      strength based on the Scottish Intercollegiate Guidelines network. Validation was
      done through peer review by the Joint Guidelines Committee of the American
      Association of Neurological Surgeons and Congress of Neurological Surgeons.
      RESULTS: Cervical laminoplasty has improved functional outcome in the setting of
      CSM or ossification of the posterior longitudinal ligament. Using the Japanese
      Orthopaedic Association scale score, approximately 55-60% average recovery rate
      has been observed (Class III). The functional improvement observed after
      laminoplasty may be limited by duration of symptoms, severity of stenosis,
      severity of myelopathy, and poorly controlled diabetes as negative risk factors
      (Class II). There is conflicting evidence regarding age, with 1 study citing it
      as a negative risk factor, and another not demonstrating this result.
      CONCLUSIONS: Cervical laminoplasty is recommended for the treatment of CSM or
      ossification of the posterior longitudinal ligament (Class III).

PMID- 19769496
TI  - Anterior cervical surgery for the treatment of cervical degenerative myelopathy.
AB  - OBJECT: The objective of this systematic review was to use evidence-based
      medicine to examine the efficacy of anterior cervical surgery for the treatment
      of cervical spondylotic myelopathy (CSM). METHODS: The National Library of
      Medicine and Cochrane Database were queried using MeSH headings and key words
      relevant to anterior cervical surgery and CSM. Abstracts were reviewed, and
      studies meeting inclusion criteria were selected. The guidelines group assembled
      an evidentiary table summarizing the quality of evidence (Classes I-III).
      Disagreements regarding the level of evidence were resolved through an expert
      consensus conference. The group formulated recommendations that contained the
      degree of strength based on the Scottish Intercollegiate Guidelines network.
      Validation was done through peer review by the Joint Guidelines Committee of the
      American Association of Neurological Surgeons/Congress of Neurological Surgeons.
      RESULTS: Mild CSM (modified Japanese Orthopaedic Association [mJOA] scale scores
      > 12) responds in the short term (3 years) to either surgical decompression or
      nonoperative therapy (prolonged immobilization in a stiff cervical collar, "low
      risk" activity modification or bed rest, and antiinflammatory medications) (Class
      II). More severe CSM responds to surgical decompression with benefits being
      maintained a minimum of 5 years and as long as 15 years postoperatively (Class
      III). CONCLUSIONS: Treatment of mild CSM may involve surgical decompression or
      nonoperative therapy for the first 3 years after diagnosis. More severe CSM (mJOA
      scale score <or= 12) should be considered for surgery depending upon the
      individual case. The shortcomings of this systematic review are that the group
      was not able to determine whether an mJOA scale score of 12 was indicative of a
      more severe CSM disease course, and whether patients who received nonsurgical
      treatment for 3 years had a significant probability for clinical deterioration
      after that time point.

PMID- 19769497
TI  - Indications for anterior cervical decompression for the treatment of cervical
      degenerative radiculopathy.
AB  - OBJECT: The objective of this systematic review was to use evidence-based
      medicine to identify the indications and utility of anterior cervical nerve root
      decompression. METHODS: The National Library of Medicine and Cochrane Database
      were queried using MeSH headings and key words relevant to surgical management of
      cervical radiculopathy. Abstracts were reviewed after which studies meeting
      inclusion criteria were selected. The guidelines group assembled an evidentiary
      table summarizing the quality of evidence (Classes I-III). Disagreements
      regarding the level of evidence were resolved through an expert consensus
      conference. The group formulated recommendations that contained the degree of
      strength based on the Scottish Intercollegiate Guidelines network. Validation was
      done through peer review by the Joint Guidelines Committee of the American
      Association of Neurological Surgeons/Congress of Neurological Surgeons. RESULTS:
      Anterior nerve root decompression via anterior cervical discectomy (ACD) with or
      without fusion for radiculopathy is associated with rapid relief (3-4 months) of
      arm/neck pain, weakness, and/or sensory loss compared with physical therapy (PT)
      or cervical collar immobilization. Anterior cervical discectomy and ACD with
      fusion (ACDF) are associated with longer term (12 months) improvement in certain
      motor functions compared to PT. Other rapid gains observed after anterior
      decompression (diminished pain, improved sensation, and improved strength in
      certain muscle groups) are also maintained over the course of 12 months. However,
      comparable clinical improvements with PT or cervical immobilization therapy are
      also present in these clinical modalities (Class I). Conflicting evidence exists
      as to the efficacy of anterior cervical foraminotomy with reported success rates
      of 52-99% but recurrent symptoms as high as 30% (Class III). CONCLUSIONS:
      Anterior cervical discectomy, ACDF, and anterior cervical foraminotomy may
      improve cervical radicular symptoms. With regard to ACD and ACDF compared to PT
      or cervical immobilization, more rapid relief (within 3-4 months) may be seen
      with ACD or ACDF with maintenance of gains over the course of 12 months (Class
      I). Anterior cervical foraminotomy is associated with improvement in clinical
      function but the quality of data are weaker (Class III), and there is a wide
      range of efficacy (52-99%).

PMID- 19769498
TI  - Techniques for anterior cervical decompression for radiculopathy.
AB  - OBJECT: The objective of this systematic review was to use evidence-based
      medicine to identify the best techniques for anterior cervical nerve root
      decompression. METHODS: The National Library of Medicine and Cochrane Database
      were queried using MeSH headings and keywords relevant to techniques for the
      surgical management of cervical radiculopathy. The guidelines group assembled an
      evidentiary table summarizing the quality of evidence (Classes I-III). The group
      formulated recommendations that contained the degree of strength based on the
      Scottish Intercollegiate Guidelines network. Validation was done through peer
      review by the Joint Guidelines Committee of the American Association of
      Neurological Surgeons/Congress of Neurological Surgeons. RESULTS: Both anterior
      cervical discectomy (ACD) and anterior cervical discectomy with fusion (ACDF) are
      equivalent treatment strategies for 1-level disease with regard to functional
      outcome (Class II). Anterior cervical discectomy with fusion may achieve a more
      rapid reduction of neck and arm pain compared to ACD with a reduced risk of
      kyphosis, although functional outcomes may be similar. Anterior cervical
      discectomy with fusion is not a lasting means of increasing foraminal or disc
      height compared to ACD. Anterior cervical plating (ACDF with instrumentation)
      improves arm pain (but not other clinical parameters) better than ACDF in the
      treatment of 2-level disease (Class II). With respect to 1-level disease, plating
      may reduce the risk of pseudarthrosis and graft problems (Class III) but does not
      necessarily improve clinical outcome alone (Class II). Cervical arthroplasty is
      recommended as an alternative to ACDF in selected patients for control of neck
      and arm pain (Class II). CONCLUSIONS: Anterior cervical discectomy, ACDF, and
      arthroplasty are effective techniques for addressing surgical cervical
      radiculopathy.

PMID- 19769499
TI  - Cervical laminoforaminotomy for the treatment of cervical degenerative
      radiculopathy.
AB  - OBJECT: The objective of this systematic review was to use evidence-based
      medicine to examine the efficacy of posterior laminoforaminotomy in the treatment
      of cervical radiculopathy. METHODS: The National Library of Medicine and Cochrane
      Database were queried using MeSH headings and key words relevant to posterior
      laminoforaminotomy and cervical radiculopathy. Abstracts were reviewed, and
      studies meeting inclusion criteria were selected. The guidelines group assembled
      an evidentiary table summarizing the quality of evidence (Classes I-III).
      Disagreements regarding the level of evidence were resolved through an expert
      consensus conference. The group formulated recommendations which contained the
      degree of strength based on the Scottish Intercollegiate Guidelines network.
      Validation was done through peer review by the Joint Guidelines Committee of the
      American Association of Neurological Surgeons/Congress of Neurological Surgeons.
      RESULTS: Posterior laminoforaminotomy improves clinical outcome in the treatment
      of cervical radiculopathy resulting from soft lateral cervical disc displacement
      or cervical spondylosis with resulting narrowing of the lateral recess. All
      studies were Class III. The most frequent design flaw involved the lack of
      utilization of validated outcomes measures. In addition, few historical studies
      included a detailed preoperative analysis of the patients. As such, the vast
      majority of studies that included both pre- and postoperative assessments with
      legitimate outcomes measures have been performed since 1990. CONCLUSIONS:
      Posterior laminoforaminotomy is an effective treatment for cervical
      radiculopathy.

PMID- 19769500
TI  - Techniques for cervical interbody grafting.
AB  - OBJECT: The objective of this systematic review was to use evidence-based
      medicine to determine the efficacy of interbody graft techniques. METHODS: The
      National Library of Medicine and Cochrane Database were queried using MeSH
      headings and keywords relevant to cervical interbody grafting. Abstracts were
      reviewed and studies that met the inclusion criteria were selected. The
      guidelines group assembled an evidentiary table summarizing the quality of
      evidence (Classes I-III). Disagreements regarding the level of evidence were
      resolved through an expert consensus conference. The group formulated
      recommendations that contained the degree of strength based on the Scottish
      Intercollegiate Guidelines network. Validation was done through peer review by
      the Joint Guidelines Committee of the American Association of Neurological
      Surgeons/Congress of Neurological Surgeons. RESULTS: Autograft bone harvested
      from the iliac crest, allograft bone from either cadaveric iliac crest or fibula,
      or titanium cages and rectangular fusion devices, with or without the use of
      autologous graft or substitute, have been successful in creating arthrodesis
      after 1- or 2-level anterior cervical discectomy with fusion (Class II).
      Alternatives to autograft, allograft, or titanium cages include
      polyetheretherketone cages and carbon fiber cages (Class III).
      Polyetheretherketone cages have been used successfully with or without
      hydroxyapatite for anterior cervical discectomy with fusion. Importantly,
      recombinant human bone morphogenic protein-2 carries a complication rate of up to
      23-27% (especially local edema) compared with 3% for a standard approach.
      CONCLUSIONS: Current evidence does not support the routine use of interbody
      grafting for cervical arthrodesis. Multiple strategies for interbody grafting
      have been successful with Class II evidence supporting the use of autograft,
      allograft, and titanium cages.

PMID- 19769501
TI  - Radiographic assessment of cervical subaxial fusion.
AB  - OBJECT: The objective of this systematic review was to use evidence-based
      medicine to identify the best methodology for radiographic assessment of cervical
      subaxial fusion. METHODS: The National Library of Medicine and Cochrane Database
      were queried using MeSH headings and keywords relevant to cervical fusion.
      Abstracts were reviewed and studies meeting inclusion criteria were selected. The
      guidelines group assembled an evidentiary table summarizing the quality of
      evidence (Classes I-III). Disagreements regarding the level of evidence were
      resolved through an expert consensus conference. The group formulated
      recommendations that contained the degree of strength based on the Scottish
      Intercollegiate Guidelines network. Validation was done through peer review by
      the Joint Guidelines Committee of the American Association of Neurological
      Surgeons/Congress of Neurological Surgeons. RESULTS: Pseudarthrosis is best
      assessed through the absence of motion detected between the spinous processes on
      dynamic radiographs (Class II). The measurement of interspinous distance on
      dynamic radiographs of >or= 2 mm is a more reliable indicator for pseudarthrosis
      than angular motion of 2 degrees based on Cobb angle measurements (Class II).
      Similarly, it is also understood that the pseudarthrosis rate will increase as
      the threshold for allowable motion on dynamic radiographs decreases. The
      combination of interspinous distance measurements and identification of bone
      trabeculation is unreliable when performed by the treating surgeon (Class II).
      Identification of bone trabeculation on static radiographs should be considered a
      less reliable indicator of cervical arthrodesis than dynamic films (Class III).
      CONCLUSIONS: Consideration should be given to dynamic radiographs and
      interspinous distance when assessing for pseudarthrosis.

PMID- 19769502
TI  - Management of anterior cervical pseudarthrosis.
AB  - OBJECT: The objective of this systematic review was to use evidence-based
      medicine to identify the best methodology for diagnosis and treatment of anterior
      pseudarthrosis. METHODS: The National Library of Medicine and Cochrane Database
      were queried using MeSH headings and key words relevant to pseudarthrosis and
      cervical spine surgery. Abstracts were reviewed, after which studies meeting
      inclusion criteria were selected. The guidelines group assembled an evidentiary
      table summarizing the quality of evidence (Classes I-III). Disagreements
      regarding the level of evidence were resolved through an expert consensus
      conference. The group formulated recommendations that contained the degree of
      strength based on the Scottish Intercollegiate Guidelines network. Validation was
      done through peer review by the Joint Guidelines Committee of the American
      Association of Neurological Surgeons/Congress of Neurological Surgeons. RESULTS:
      Evaluation for pseudarthrosis is warranted, as there may be an association
      between clinical outcome and pseudarthrosis. The strength of this association
      cannot be accurately determined because of the variable incidence of symptomatic
      and asymptomatic pseudarthroses (Class III). Revision of a symptomatic
      pseudarthrosis may be considered because arthrodesis is associated with improved
      clinical outcome (Class III). Both posterior and anterior approaches have proven
      successful for surgical correction of an anterior pseudarthrosis. Posterior
      approaches may be associated with higher fusion rates following repair of an
      anterior pseudarthrosis (Class III). CONCLUSIONS: If suspected, pseudarthrosis
      should be investigated because there may be an association between arthrodesis
      and outcome. However, the strength of this association cannot be accurately
      determined. Anterior and posterior approaches have been successful.

PMID- 19769503
TI  - Functional outcomes assessment for cervical degenerative disease.
AB  - OBJECT: The objective of this systematic review was to use evidence-based
      medicine to identify valid, reliable, and responsive measures of functional
      outcome after treatment for cervical degenerative disease. METHODS: The National
      Library of Medicine and Cochrane Database were queried using MeSH headings and
      key words relevant to functional outcomes. Abstracts were reviewed after which
      studies meeting inclusion criteria were selected. The guidelines group assembled
      an evidentiary table summarizing the quality of evidence (Classes I-III).
      Disagreements regarding the level of evidence were resolved through an expert
      consensus conference. The group formulated recommendations that contained the
      degree of strength based on the Scottish Intercollegiate Guidelines network.
      Validation was done through peer review by the Joint Guidelines Committee of the
      American Association of Neurological Surgeons/Congress of Neurological Surgeons.
      RESULTS: Myelopathy Disability Index, Japanese Orthopaedic Association scale, 36
      Item Short Form Health Survey, and gait analysis were found to be valid and
      reliable measures (Class II) for assessing cervical spondylotic myelopathy. The
      Patient-Specific Functional Scale, the North American Spine Society scale, and
      the Neck Disability Index were found to be reliable, valid, and responsive (Class
      II) for assessing radiculopathy for nonoperative therapy. The Cervical Spine
      Outcomes Questionnaire was a reliable and valid method (Class II) to assess
      operative therapy for cervical radiculopathy. CONCLUSIONS: Several functional
      outcome measures are available to assess cervical spondylotic myelopathy and
      cervical radiculopathy.

PMID- 19769504
TI  - Electrophysiological monitoring during surgery for cervical degenerative
      myelopathy and radiculopathy.
AB  - OBJECT: The objective of this systematic review was to use evidence-based
      medicine to examine the diagnostic and therapeutic utility of intraoperative
      electrophysiological (EP) monitoring in the surgical treatment of cervical
      degenerative disease. METHODS: The National Library of Medicine and Cochrane
      Database were queried using MeSH headings and key words relevant to cervical
      spine surgery and EP monitoring. The guidelines group assembled an evidentiary
      table summarizing the quality of evidence (Classes I-III). The group formulated
      recommendations that contained the degree of strength based on the Scottish
      Intercollegiate Guidelines network. Validation was done through peer review by
      the Joint Guidelines Committee of the American Association of Neurological
      Surgeons/Congress of Neurological Surgeons. RESULTS: The reliance on changes in
      EP monitoring as an indication to alter a surgical plan or administer steroids
      has not been observed to reduce the incidence of neurological injury during
      routine surgery for cervical spondylotic myelopathy or cervical radiculopathy
      (Class III). However, there is an absence of study data examining the benefit of
      altering a surgical plan due to EP changes. CONCLUSIONS: Although the use of EP
      monitoring may serve as a sensitive means to diagnose potential neurological
      injury during anterior spinal surgery for cervical spondylotic myelopathy, the
      practitioner must understand that intraoperative EP worsening is not specific-it
      may not represent clinical worsening and its recognition does not necessarily
      prevent neurological injury, nor does it result in improved outcome (Class II).
      Intraoperative improvement in EP parameters/indices does not appear to forecast
      outcome with reliability (conflicting Class I data).

PMID- 19769505
TI  - Anatomy of the sacral nerve roots: clinical implications for neural repair.

PMID- 19769506
TI  - Measurements and mapping of 282,420 nerve fibers in the S1-5 nerve roots.
AB  - OBJECT: The study aims to analyze nerve fiber types in the sacral nerve roots as
      a prerequisite for stimulation. METHODS: One-micrometer cross-sections of human
      ventral and dorsal S1-5 roots were stained with osmium and toluidine blue. The
      total fiber diameter and myelin sheath were measured in 282,420 nerve fibers.
      RESULTS: The analysis revealed the following 3 main nerve fiber types: Aalpha
      fibers (diameter 6-14 microm), Agamma fibers (diameter 2-4 microm), and B fibers
      (diameter < 2 microm). The B fibers were absent in S-1, present in some S-2
      fascicles, and abundant from S-3 to S-5. The Aalpha fibers dominated the S-1
      roots and most fascicles of S-2 roots. In the S3-5 roots, only a few Aalpha
      fibers were present. The relative occurrence of Agamma fibers increased from S-1
      to S-5. In dorsal roots, Agamma fibers represented approximately 70% of all nerve
      fibers in every root and fascicle. CONCLUSIONS: The B fibers represented efferent
      parasympathetic fibers. These fibers were concentrated in certain areas of the
      nerve roots, not randomly distributed. The Aalpha fibers innervate lower
      extremity muscles and sphincters. The inverse correlation of Aalpha and Agamma
      fibers in the ventral roots from S-1 to S-5 is surprising. In dorsal roots,
      Agamma fibers may conduct pain, touch, and temperature signals. Highly selective
      fiber stimulation specific for type, location, and direction may improve sacral
      nerve stimulation for a spastic bladder in paraplegic individuals.

PMID- 19769507
TI  - Mean subaxial space available for the cord index as a novel method of measuring
      cervical spine geometry to predict the chronic stinger syndrome in American
      football players.
AB  - OBJECT: The chronic stinger syndrome is a distinct entity from acute stingers and
      has been shown to have its own pathophysiology that, unlike acute stingers, may
      reflect long-standing geometrical changes of the subaxial spinal canal and
      chronic irritation/degeneration of the exiting nerve root complex. There is no
      method available, however, to accurately predict these symptoms in athletes. The
      mean subaxial cervical space available for the cord (MSCSAC) is a novel
      alternative to the Torg ratio for predicting neurological symptoms caused by
      cervical spondylosis in elite athletes. It is the goal of this study to determine
      critical values for this measurement index and to retrospectively correlate those
      values to neurological symptoms. METHODS: Magnetic resonance images obtained in
      103 male athletes participating in the 2005 and 2006 National Football League
      Scouting Combine and a control group of 42 age-matched male nonathletes were
      retrospectively reviewed. The Torg ratio and SAC values were calculated in
      triplicate at each cervical level from C3-6 by using lateral radiographs and
      midsagittal T2-weighted MR images of the cervical spine, respectively. These
      values were then averaged for each individual to produce mean subaxial cervical
      Torg ratio (MSCTR) and MSCSAC values. Receiver operating characteristic curves
      were constructed for each measurement technique and were compared based on their
      respective area under the curves (AUCs). RESULTS: The MSCSAC difference between
      athletes with and without chronic stingers was statistically significant (p <
      0.01). The difference between athletes with and without chronic stingers compared
      with controls was also statistically significant (p < 0.001 and p < 0.001,
      respectively). The AUC for the MSCSAC was 0.813, which was significantly greater
      than the AUC for both the MSCTR (p = 0.0475) and the individual Torg ratio (p =
      0.0277). The MSCTR had the second largest AUC (0.676) and the conventional method
      of measuring individual Torg ratio values produced the lowest AUC (0.661). It was
      found that using the MSCSAC with a critical value of 5.0 mm produced a
      sensitivity of 80% and a negative likelihood ratio of 0.23 for predicting chronic
      stingers. Lowering the cutoff value to 4.3 mm for the MSCSAC resulted in a
      possible confirmatory test with a specificity of 96% and a positive likelihood
      ratio of 13.25. CONCLUSIONS: A critical value of 5.0 mm for the MSCSAC provides
      the clinician with a screening test for chronic stingers and anything < 4.3 mm
      adds additional confidence as a confirmatory test. These results are
      approximately 20% more accurate than the classic Torg ratio based on our AUC
      analysis. It was found that measuring the spinal geometry throughout the length
      of the subaxial cervical spine produced a more reliable method by which to
      predict neurological symptoms than the traditional approach of measuring
      individual levels. This shows that the underlying pathogenesis of the chronic
      stinger syndrome is best characterized as a process that involves the entire
      subaxial region uniformly.

PMID- 19769508
TI  - Thoracic vertebrectomy and spinal reconstruction via anterior, posterior, or
      combined approaches: clinical outcomes in 91 consecutive patients with metastatic
      spinal tumors.
AB  - OBJECT: Adequate decompression of the thoracic spinal cord often requires a
      complete vertebrectomy. Such procedures can be performed from an
      anterior/transthoracic, posterior, or combined approach. In this study, the
      authors sought to compare the clinical outcomes of patients with spinal
      metastatic tumors undergoing anterior, posterior, and combined thoracic
      vertebrectomies to determine the efficacy and operative morbidity of such
      approaches. METHODS: A retrospective review was conducted of all patients
      undergoing thoracic vertebrectomies at a single institution over the past 7
      years. Characteristics of patients and operative procedures were documented.
      Neurological status, perioperative variables, and complications were assessed and
      associations with each approach were analyzed. RESULTS: Ninety-one patients (mean
      age 55.5 +/- 13.7 years) underwent vertebrectomies via an anterior (22 patients,
      24.2%), posterior (45 patients, 49.4%), or combined anterior-posterior approach
      (24 patients, 26.4%) for metastatic spinal tumors. The patients did not differ
      significantly preoperatively in terms of neurological assessments on the Nurick
      and American Spinal Injury Association Impairment scales, ambulatory ability, or
      other comorbidities. Anterior approaches were associated with less blood loss
      than posterior approaches (1172 +/- 1984 vs 2486 +/- 1645 ml, respectively; p =
      0.03) or combined approaches (1172 +/- 1984 vs 2826 +/- 2703 ml, respectively; p
      = 0.05) but were associated with a similar length of stay compared with the other
      treatment cohorts (11.5 +/- 9.3 [anterior] vs 11.3 +/- 8.6 [posterior] vs 14.3 +/
      6.7 [combined] days; p = 0.35). The posterior approach was associated with a
      higher incidence of wound infection compared with the anterior approach cohort
      (26.7 vs 4.5%, respectively; p = 0.03), and patients in the posterior approach
      group experienced the highest rates of deep vein thrombosis (15.6% [posterior] vs
      0% [other 2 groups]; p = 0.02). However, the posterior approach demonstrated the
      lowest incidence of pneumothorax (4.4%; p < 0.0001) compared with the other 2
      cohorts. Duration of chest tube use was greater in the combined patient group
      compared with the anterior approach cohort (8.8 +/- 6.2 vs 4.7 +/- 2.3 days,
      respectively; p = 0.01), and the combined group also experienced the highest
      rates of radiographic pleural effusion (83.3%; p = 0.01). Postoperatively, all
      groups improved neurologically, although functional outcome in patients
      undergoing the combined approach improved the most compared with the other 2
      groups on both the Nurick (p = 0.04) and American Spinal Injury Association
      Impairment scales (p = 0.03). CONCLUSIONS: Decisions regarding the approach to
      thoracic vertebrectomy may be complex. This study found that although anterior
      approaches to the thoracic vertebrae have been historically associated with
      significant pulmonary complications, in our experience these rates are
      nevertheless quite comparable to that encountered via a posterior or combined
      approach. In fact, the posterior approach was found to be associated with a
      higher risk for some perioperative complications such as wound infection and deep
      vein thromboses. Finally, the combined anteriorposterior approach may provide
      greater ambulatory and neurological improvements in properly selected patients.

PMID- 19769509
TI  - Staged sacrectomy--an adaptive approach.
AB  - Object Sacral tumors are commonly diagnosed late and therefore present at an
      advanced stage. The late presentation makes curative surgery technically
      demanding. Sacrectomy is fraught with a high local recurrence rate and potential
      complications: deep infection; substantial blood loss; large-bone and soft-tissue
      defects; bladder, bowel, and sexual dysfunction; spinopelvic nonunion; and gait
      disturbance. The aim of this study was to analyze the complications and morbidity
      of sacrectomy and the modifications meant to reduce the morbidity. Methods This
      is a retrospective study of the patients who underwent sacrectomy between
      February 1997 and September 2008 in the Department of Surgical Oncology,
      Government Royapettah Hospital, Kilpauk Medical College, in Chennai, Tamilnadu,
      India. Sacrectomy was performed using 1 of the following approaches: posterior
      approach, abdominolateral approach, or abdominosacral approach, either as
      sequential or staged operations. The morbidity rate after the sequential and
      staged abdominosacral approaches was analyzed. Functional assessment was made
      based on the Enneking functional scoring system. The results were analyzed and
      survival analysis was done using the Kaplan-Meier method (with SPSS software).
      Results Nineteen patients underwent sacrectomy, of which 12 operations were
      partial, 3 were subtotal, and 4 were total sacrectomy. Histological diagnosis
      included giant cell tumor, chordoma, chondroblastoma, adenocarcinoma of rectum,
      and retroperitoneal sarcoma. The giant cell tumor was the most common tumor in
      this series, followed by chordoma. The patients' mean age at diagnosis was 32
      years. There were 10 male and 9 female patients. Fortyseven percent of patients
      had bowel and bladder disturbances postoperatively, and 57.89% of patients had
      wound complications. The median follow-up duration was 24 months (range 2-140
      months). The 5-year overall survival rate was 70.4%, and the 5-year disease-free
      survival rate was 65% (based on the Kaplan-Meier method). The local recurrence
      rate (5 cases) was 26.32%. The median duration for first recurrence was 12 months
      (range 3-17 months). Distant metastasis occurred in 1 patient (5.26%), and 4
      patients died, 1 of them due to pulmonary thromboembolism, in the postoperative
      period. Based on the Enneking system of functional evaluation, 5 patients
      (26.32%) had excellent outcome, 6 (31.57%) had good outcome, 5 (26.32%) had fair
      outcome, and 3 (15.78%) had poor outcome. Spinopelvic reconstruction was not
      performed in any of the patients, and all were ambulatory postoperatively. The
      staged abdominosacral approach has markedly reduced patient morbidity in terms of
      reduction of operating time, blood loss, anesthesia complications, and wound
      complications. Conclusions Sacrectomy, a dreaded operation that often results in
      morbidity, is now feasible with modifications and improvement in surgical
      technique. The staged abdominosacral approach reduces the immediate postoperative
      morbidity. Use of a gluteal advancement flap reduces the incidence of wound
      complications. With modern surgical facilities and postoperative care, sacrectomy
      is feasible via the staged abdominosacral approach.

PMID- 19769510
TI  - Comparison of thoracolumbosacral orthosis and no orthosis for the treatment of
      thoracolumbar burst fractures: interim analysis of a multicenter randomized
      clinical equivalence trial.
AB  - OBJECT: The authors compared the outcome of patients with thoracolumbar burst
      fractures treated with and without a thoracolumbosacral orthosis (TLSO). METHODS:
      As of June 2002, all consecutive patients satisfying the following inclusion
      criteria were considered eligible for this study: 1) the presence of an AO
      Classification Type A3 burst fractures between T-11 and L-3, 2) skeletal maturity
      and age < 60 years, 3) admission within 72 hours of injury, 4) initial kyphotic
      deformity < 35 degrees, and 5) no neurological deficit. The study was designed as
      a multicenter prospective randomized clinical equivalence trial. The primary
      outcome measure was the score based on the Roland-Morris Disability Questionnaire
      assessed at 3 months postinjury. Secondary outcomes are assessed until 2 years of
      follow-up have been reached, and these domains included pain, functional outcome
      and generic health-related quality of life, sagittal alignment, length of
      hospital stay, and complications. Patients in whom no orthotic was used were
      encouraged to ambulate immediately following randomization, maintaining "neutral
      spinal alignment" for 8 weeks. The patients in the TLSO group began being weaned
      from the brace at 8 weeks over a 2-week period. RESULTS: Sixty-nine patients were
      followed to the primary outcome time point, and 47 were followed for up to 1
      year. No significant difference was found between treatment groups for any
      outcome measure at any stage in the follow-up period. There were 4 failures
      requiring surgical intervention, 3 in the TLSO group and 1 in the non-TLSO group.
      CONCLUSIONS: This interim analysis found equivalence between treatment with a
      TLSO and no orthosis for thoracolumbar AO Type A3 burst fractures. The influence
      of a brace on early pain control and function and on long-term 1- and 2-year
      outcomes remains to be determined. However, the authors contend that a
      thoracolumbar burst fracture, in exclusion of an associated posterior ligamentous
      complex injury, is inherently a very stable injury and may not require a brace.

PMID- 19769511
TI  - Neurological outcome after surgical management of adult tethered cord syndrome.
AB  - OBJECT: Although postsurgical neurological outcomes in patients with tethered
      cord syndrome (TCS) are well known, the rate and development of neurological
      improvement after first-time tethered cord release is incompletely understood.
      The authors reviewed their institutional experience with the surgical management
      of adult TCS to assess the time course of symptomatic improvement, and to
      identify the patient subgroups most likely to experience improvement of motor
      symptoms. METHODS: The authors retrospectively reviewed 29 consecutive cases of
      first-time adult tethered cord release. Clinical symptoms of pain and motor and
      urinary dysfunction were evaluated at 1 and 3 months after surgery, and then
      every 6 months thereafter. Rates of improvement in pain and motor or urinary
      dysfunction over time were identified, and presenting factors associated with
      improvement of motor symptoms were assessed using a multivariate survival
      analysis (Cox model). RESULTS: The mean patient age was 38 +/- 13 years. The
      causes of TCS included lipomyelomeningocele in 3 patients (10%), tight filum in 3
      (10%), lumbosacral lipoma in 4 (14%), intradural tumor in 3 (10%), previous
      lumbosacral surgery in 2 (7%), and previous repair of myelomeningocele in 14
      (48%). The mean +/- SD duration of symptoms before presentation was 5 +/- 7
      months. Clinical presentation included diffuse pain/parasthesias in both lower
      extremities in 13 patients (45%), or perineal distribution in 18 (62%), lower
      extremity weakness in 17 (59%), gait difficulties in 17 (59%), and bladder
      dysfunction in 14 (48%). Laminectomy was performed in a mean of 2.5 +/- 0.7
      levels per patient, and 9 patients (30%) received duraplasty. At 18 months
      postoperatively, 47% of patients had improved urinary symptoms, 69% had improved
      lower extremity weakness and gait, and 79% had decreased painful dysesthesias.
      Median time to symptomatic improvement was least for pain (1 month), then motor
      (2.3 months), and then urinary symptoms (4.3 months; p = 0.04). In patients
      demonstrating improvement, 96% improved within 6 months of surgery. Only 4%
      improved beyond 1-year postoperatively. In a multivariate analysis, the authors
      found that patients who presented with asymmetrical lower extremity weakness (p =
      0.0021, hazard ratio 5.7) or lower extremity hyperreflexia (p = 0.037, hazard
      ratio = 4.1) were most likely to experience improvement in motor symptoms.
      CONCLUSIONS: In the authors' experience, pain and motor and urinary dysfunction
      improve postoperatively in the majority of patients. The rate of symptomatic
      improvement was greatest for pain resolution, followed by motor, and then urinary
      improvement. Patients who experienced improvement in any symptom had done so by 6
      months after tethered cord release. Patients with asymmetrical motor symptoms or
      lower extremity hyperreflexia at presentation were most likely to experience
      improvements in motor symptoms. These findings may help guide patient education
      and surgical decision-making.

PMID- 19769512
TI  - Image classification of idiopathic spinal cord herniation based on symptom
      severity and surgical outcome: a multicenter study.
AB  - OBJECT: The purpose of this study was to provide the first evidence for image
      classification of idiopathic spinal cord herniation (ISCH) in a multicenter
      study. METHODS: Twelve patients who underwent surgery for ISCH were identified,
      and preoperative symptoms, severity of paralysis and myelopathy, disease
      duration, plain radiographs, MR imaging and CT myelography findings, surgical
      procedure, intraoperative findings, data from spinal cord monitoring, and
      postoperative recovery were investigated in these patients. Findings on sagittal
      MR imaging and CT myelography were classified into 3 types: a kink type (Type K),
      a discontinuous type (Type D), and a protrusion type (Type P). Using axial
      images, the location of the hiatus was classified as either central (Type C) or
      lateral (Type L), and the laterality of the herniated spinal cord was classified
      based on correspondence (same; Type S) or noncorrespondence (opposite; Type O)
      with the hiatus location. A bone defect at the ISCH site and the laterality of
      the defect were also noted. RESULTS: Patients with Type P herniation had a good
      postoperative recovery, and those with a Type C location had significant severe
      preoperative lower-extremity paralysis and a significantly poor postoperative
      recovery. Patients with a bone defect had a significantly severe preoperative
      myelopathy, but showed no difference in postoperative recovery. CONCLUSIONS: The
      authors' results showed that a Type C classification and a bone defect have
      strong relationships with severity of symptoms and surgical outcome and are
      important imaging and clinical features for ISCH. These findings may allow
      surgeons to determine the severity of preoperative symptoms and the probable
      surgical outcome from imaging.

PMID- 19769513
TI  - Management of delayed esophageal perforations after anterior cervical spinal
      surgery.
AB  - OBJECT: Delayed esophageal perforation is an uncommon but well-known complication
      after anterior cervical spine surgery. To the authors' knowledge there is no
      consensus to the optimal management of these patients in the literature. METHODS:
      The authors performed a retrospective review of 5 cases involving patients who
      were referred to their institution for the management of delayed esophageal
      perforations after undergoing anterior cervical spine surgery for a variety of
      reasons. RESULTS: The primary presenting symptom in all 5 patients was dysphagia.
      All patients initially underwent primary closure of the perforation with a
      sternocleidomastoid muscle flap. One patient required multiple surgeries to
      correct the perforation and ultimately required a free flap. CONCLUSIONS: The
      authors recommend a multidisciplinary approach that involves otolaryngological
      surgeons as well as spine surgeons. They recommend removal of all anterior
      hardware and believe that it is essential to the treatment of esophageal
      perforations. If the patient does not have evidence of fusion at the time of
      presentation, then posterior cervical instrumentation is a viable alternative.

PMID- 19769514
TI  - Positional vertebral artery compression and vertebrobasilar insufficiency due to
      a herniated cervical disc.
AB  - The authors report a case of vertebrobasilar insufficiency caused by vertebral
      artery (VA) compression due to a herniated cervical disc, which was surgically
      treated with the aid of intraoperative angiography. This 78-year-old man visited
      the hospital because of syncope following head rotation. Admission CT scans
      revealed a calcified mass adjacent to the right lateral process of the C-4 spine.
      Cervical angiography demonstrated an obstruction of the right VA at this region
      on rotation of the head to the right. The operation revealed a cervical disc
      protruding toward the right VA. The disc was surgically removed, and then the
      decompression of the right VA was confirmed on intraoperative angiography
      studies. A histopathological examination showed fibrohyaline cartilage,
      indicating an ossified intervertebral disc. The postoperative course was
      uneventful, and he has not experienced any syncope since treatment. A cervical
      disc herniation could be a cause of vertebrobasilar insufficiency by exerting
      positional compression of the VA. Intraoperative angiography could be quite
      useful to confirm this condition during decompression surgery for a cervical VA.

PMID- 19769515
TI  - Anterior and posterior decompressive surgery for progressive amyotrophy
      associated with cervical spondylosis: a retrospective study of 51 patients.
AB  - OBJECT: The aims of this study were to review the clinicoradiological findings in
      patients who underwent decompressive surgery for proximal and distal types of
      muscle atrophy caused by cervical spondylosis and to discuss the outcome and
      techniques of surgical intervention. METHODS: Fifty-one patients (43 men and 8
      women) with proximal (37, with arm drop) and distal muscle atrophy (14, with
      wrist drop) underwent cervical decompression (39 anterior decompressions and 12
      open-door C3-7 laminoplasties with microsurgical foraminotomy) for muscle
      weakness in the upper extremities. The clinical course, type of spinal cord
      compression, abnormal signal intensity on high-resolution MR imaging, and
      postdecompression improvement in muscle power were reviewed at a mean follow-up
      of 2.6 years (range 0.8-9.4 years). RESULTS: The most commonly affected vertebrae
      were C4-5 and C5-6, and C5-6 and C6-7 in patients with proximal or distal muscle
      atrophy, respectively; the respective numbers of affected vertebrae were 1.5 and
      2.2. Transaxial MR imaging showed medial compression of the spinal cord in 20
      patients (in 12 with proximal and 8 with distal muscle atrophy), paramedial
      compression in 22 (17 and 5 patients, respectively), and foraminal compression in
      9 (8 and 1 patient, respectively). Increased signal intensity on MR imaging was
      observed in 85.0, 22.7, and 11.1% of cases of medial, paramedial, and foraminal
      compression, respectively. Increased signal intensity at the affected muscle
      segment level was observed in 52.9, 40.0, and 0% of cases, respectively. Sixty
      two percent of patients with proximal muscle atrophy gained 1 or more grades of
      muscle power on manual muscle testing (MMT), whereas 64.3% with distal muscle
      atrophy failed to gain even 1 grade of improvement. The recovery of muscle power
      correlated with disease duration and the percent voltage of Erb point or wrist
      stimulated muscle evoked potentials but not with preoperative MMT, longitudinal
      range of spinal cord compression, signal change on T2-weighted MR imaging, or
      surgical procedure. CONCLUSIONS: Surgical outcome in patients with distal muscle
      atrophy was inferior to that in patients with proximal atrophy. The distal type
      was characterized by a long preoperative period, a greater number of cervical
      spine misalignments, a narrow spinal canal, and increased signal intensity on T2
      weighted MR imaging. It is essential to perform a careful neurological
      evaluation, including sensory examination of the lower limbs, as well as
      neuroradiological and neurophysiological assessments to avoid confusion with
      motor neuron disease and to detect the coexistence of amyotrophic lateral
      sclerosis, especially when surgical treatment of cervical spondylosis is planned.
      The results of careful physical examination, MR imaging studies, and
      electromyography studies should be comprehensively evaluated to ascertain the
      pathophysiology of the muscle atrophy. It is very important to distinguish the
      pathophysiology caused by nerve root impingements from anterior horn dysfunction
      when making decisions about treatment strategy. Surgical treatment--with or
      without foraminotomy--for amyotrophy in cervical spondylosis requires urgent
      action with regard to human neuroanatomy and neural innervation of the paralyzed
      muscles.

PMID- 19769516
TI  - Biomechanics of C-7 transfacet screw fixation.
AB  - OBJECT: The small diameter of the pedicle can make C-7 pedicle screw insertion
      dangerous. Although transfacet screws have been studied biomechanically when used
      in pinning joints, they have not been well studied when used as part of a C7-T1
      screw/rod construct. The authors therefore compared C7-T1 fixation using a C-7
      transfacet screw/T-1 pedicle screw construct with a construct composed of pedicle
      screws at both levels. METHODS: Each rigid posterior screw/rod construct was
      placed in 7 human cadaveric C6-T2 specimens (14 total). Specimens were tested in
      normal condition, after 2-column instability, and once fixated. Nondestructive,
      nonconstraining pure moments (maximum 1.5 Nm) were applied to induce flexion,
      extension, lateral bending, and axial rotation while recording 3D motion
      optoelectronically. The entire construct was then loaded to failure by dorsal
      linear force. RESULTS: There was no significant difference in angular range of
      motion between the 2 instrumented groups during any loading mode (p > 0.11,
      nonpaired t-tests). Both constructs reduced motion to < 2 degrees in any
      direction and allowed significantly less motion than in the normal condition. The
      C-7 facet screw/T-1 pedicle screw construct allowed a small but significantly
      greater lax zone than the pedicle screw/rod construct during lateral bending, and
      it failed under significantly less load than the pedicle screw/rod construct (p <
      0.001). CONCLUSIONS: When C-7 transfacet screws are connected to T-1 pedicle
      screws, they provide equivalent stability of constructs formed by pedicle screws
      at both levels. Although less resistant to failure, the transfacet screw
      construct should be a viable alternative in patients with healthy bone.

PMID- 19769517
TI  - Iatrogenic intradural spinal arachnoid cyst as a complication of lumbar spine
      surgery.
AB  - Iatrogenic spinal arachnoid cysts are rare, but have been described as a
      complication of spinal injection and lumbar puncture procedures. The authors
      describe 2 cases of iatrogenic spinal arachnoid cyst formation that occurred
      after incidental durotomy during lumbar spine surgery. In both cases,
      postoperative MR imaging revealed compression of the cauda equina by an
      intradural arachnoid cyst. Intradural exploration and fenestration of the
      arachnoid cyst was accomplished in each case. This entity should be considered in
      the differential diagnosis of a patient experiencing symptoms of neurological
      compression after a lumbar surgery complicated by incidental durotomy.

PMID- 19769518
TI  - Functional and clinical evaluation for the surgical treatment of degenerative
      stenosis of the lumbar spinal canal.
AB  - OBJECT: This study was designed to evaluate the efficacy of decompressive surgery
      for degenerative lumbar spinal stenosis (LSS) on a functional and clinical basis.
      METHODS: A prospective analysis and follow-up of 125 consecutive patients with
      degenerative LSS between 2000 and 2006 were performed. All patients underwent
      surgery for lumbar stenosis. Functional evaluations of the patients were
      performed using a treadmill, the visual analog scale, and the Oswestry Disability
      Questionnaire (ODQ). These parameters were recorded before surgery and the 3rd
      month and 1st and 2nd years after treatment. The first symptom time (FST),
      maximal walking duration (MWD), and thecal sac cross-sectional area (CSA) before
      and after surgery were also recorded. Statistical relations between variables
      were calculated. RESULTS: As patient ages increased, the CSA of the thecal sac
      decreased. Decompressive surgery reached the target according to the difference
      between the preoperative and postoperative thecal sac CSA. A correlation between
      the CSA of the thecal sac and FST, and between the CSA of the thecal sac and MWD
      could not be established. There was a significant correlation between the FST and
      MWD, and a negative correlation could be established between the MWD and the ODQ
      score. Surgery led to significant decreases in the ODQ score. Maximal improvement
      was observed in the 3rd month after decompressive surgery. CONCLUSIONS: The
      treatment for LSS should be decided using functional criteria; radiological
      criteria may not correlate with the severity of the disease. Improvements
      following lumbar decompression surgery continued within 1 year of treatment
      according to the ODQ and did not change significantly thereafter.

PMID- 19769519
TI  - Traumatic burst fracture in a patient with a lumbar artificial disc.
AB  - Lumbar disc arthroplasty is now a common treatment for lumbar degenerative disc
      disease. Whereas the immediate and delayed complications in patients with
      artificial lumbar discs are well reported, the durability of artificial disc
      hardware after severe spine trauma is unknown. The authors describe the
      management of a rare case of a traumatic lumbar burst fracture in a patient who
      had undergone disc arthroplasty. This 31-year-old male contractor had undergone
      placement of an L4-5 Charite artificial disc (DePuy Spine) and L5-S1 anterior
      lumbar fusion 10 months before he fell from a roof and sustained a traumatic L-3
      burst fracture with significant canal compromise and cauda equina injury. Despite
      the considerable compressive load on his spine, the artificial disc (L4-5)
      remained intact without any radiological signs of hardware failure, and the
      vertebrae above (L-4) and below (L-5) the artificial disc had no signs of injury.
      For the L-3 burst fracture the patient underwent an open decompressive
      laminectomy at L2-3 and posterior fusion with instrumentation from L-2 to L-4. At
      24 months postinjury, he had returned to full work activities as a contractor
      with minimal back pain and mild right lower-extremity sensory changes and
      weakness left over from the trauma. The total disc arthroplasty at L4-5 is
      functional and has preserved motion, and there is a solid fusion at L2-4 and L5
      S1. This case demonstrates that a lumbar artificial disc can tolerate a
      significant load from trauma and remain functional without hardware failure even
      after a traumatic burst fracture at the adjacent lumbar vertebral body and shows
      the successful treatment of this fracture, with posterior fusion preserving the
      motion of an artificial disc.

PMID- 19769520
TI  - Epidural steroid injection resulting in epidural hematoma in a patient despite
      strict adherence to anticoagulation guidelines.
AB  - Epidural steroid injections are relatively safe procedures, although the risk of
      hemorrhagic complications in patients undergoing long-term anticoagulation
      therapy is higher. The American Society for Regional Anesthesia and Pain Medicine
      has specific guidelines for treatment of these patients when they undergo
      neuraxial anesthetic procedures. In this paper, the authors present a case in
      which the current American Society for Regional Anesthesia and Pain Medicine
      guidelines were strictly followed with respect to withholding and reintroducing
      warfarin and enoxaparin after an epidural steroid injection, but the patient
      nevertheless developed a spinal epidural hematoma requiring emergency surgical
      evacuation. The authors compare the case with the 8 other published cases of
      postinjection epidural hematomas in patients with coagulopathy, and the specific
      risk factors that may have contributed to the hemorrhagic complication in this
      patient is analyzed.

PMID- 19769521
TI  - Complications in the management of Charcot spinal arthropathy.
AB  - Charcot spinal arthropathy is a relatively rare, destructive process
      characterized by a cycle of progressive deformity, destruction, and worsening
      instability as a result of repetitive trauma and inflammation. It may result from
      nontraumatic as well as traumatic causes. Historically, patients with severe
      symptomatic instability have been successfully treated with combined anterior and
      posterior fusion techniques. The long-term outcomes and potential complications,
      however, have not been well reported. The authors report on 2 such cases of
      Charcot spinal arthropathy treated surgically, one with a traumatic and one with
      a nontraumatic etiology. They include the unique pitfalls encountered while
      treating these patients, as well as their surgical treatments, complications, and
      long-term results.

PMID- 19769522
TI  - Electromyography in the detection of mechanically induced spinal motor tract
      injury: observations in diverse porcine models.
AB  - OBJECT: Porcine spinal cords were mechanically injured at the thoracic level
      while recording muscle-derived electrically stimulated transcranial motor evoked
      potentials (TcMEPs) and electromyography (EMG) readings from the same electrode
      derivations. The authors postulated that midthoracic spinal cord injury caused by
      diverse methods can trigger hindlimb EMG activity. Early detection of hindlimb
      EMG activity may permit avoidance of motor conduction block (TcMEP loss).
      METHODS: Twelve pigs underwent midthoracic spinal cord exposure. Spinal cord
      sectioning was performed to define dorsal column versus lateral spinal cord
      contribution to muscle-derived electrically stimulated spinal cord motor evoked
      potentials (SC MEPs) and TcMEPs (in 2 pigs). A bipolar needle stimulator was
      placed within intramedullary sites to 1) acquire electrically stimulated motor
      evoked potentials in the hindlimbs, and 2) induce mechanically stimulated
      hindlimb EMG activity at sites responsive to electrical stimulation (in 2 pigs).
      Transcranial MEPs and EMG recordings were observed during spinal cord distraction
      (in 3 pigs), slow and rapid extradural spinal cord compression with a metal
      caliper (in 3 pigs), and rapid extradural spinal cord compression with a spring
      loaded clip (in 2 pigs). RESULTS: Lateral cord (but not dorsal column) sectioning
      abolished both SC MEPs and TcMEPs. Intramedullary electrical and mechanical
      stimulation within the lateral (but not dorsal) cord elicited ipsilateral
      hindlimb MEPs and EMG activity ("EMG injury discharge"), respectively.
      Distraction inconsistently produced EMG injury discharges concomitant with TcMEP
      loss. Rapid extradural spinal cord compression with a metal caliper or spring
      loaded clip consistently induced EMG injury discharges (in 4 of 4 pigs); slow
      compression did not elicit EMG activity. Brief extradural spring-loaded clip
      compressions (1-2 seconds) elicited EMG injury discharges without TcMEP loss; 14
      second clip compression effected EMG injury discharges and TcMEP loss, which
      recovered after clip removal. CONCLUSIONS: Electromyographic activity (referred
      to as "EMG injury discharges" in the present study) can be elicited both by
      intramedullary manipulation and rapidly applied transaxial spinal cord
      compression. Preliminary observations suggest that these EMG injury discharges
      precede and may anticipate TcMEP loss. Presumably, rapid deformation of spinal
      motor tracts (which appear to lie within the lateral porcine spinal cord)
      generates descending volleys which can bring to firing threshold lumbar motor
      neurons (and recording of EMG injury discharges). Intraoperative neuromonitoring
      of high-risk spinal surgeries at the spinal cord level may benefit from the
      addition of EMG recording to tests of spinal cord motor conduction such as TcMEP.
      Further clinical trials are required to examine EMG efficacy in this context.

PMID- 19769523
TI  - Minimally invasive surgery and radiation exposure.

PMID- 19769525
TI  - Goat bone tissue engineering: comparing an intramuscular with a posterolateral
      lumbar spine location.
AB  - The aim of this study was to investigate the effect of implant location on bone
      formation in goats using autologous bone marrow-derived stromal cells in porous
      calcium phosphate scaffolds. Intramuscular locations were compared to
      posterolateral spine fusion locations in eight goats. As scaffolds, we used
      biphasic calcium phosphate porous blocks of 5 x 5 x 5 mm. Cell-seeded implants
      were compared to empty controls. Bone marrow-derived stromal cells were seeded at
      8 million cells per cm(3) scaffold and cultured for 1 week. The follow-up time
      was 12 weeks. Fluorochromes were administered intravenously at 4, 6, and 8 weeks.
      Ectopic implants showed 21 +/- 3.6% bone formation for the cell seeded and 2.0 +/
      3.0% for the controls (p < 0.001). Paraspinal implants, however, showed 0.10 +/-
      0.13% in the cell seeded compared to 0.023 +/- 0.027% in the control group (p =
      0.09). A benefit of the cells was only found in the area closest to the
      paraspinal muscles (p < 0.01). Bone formation in the control samples was of later
      onset compared to the cell-seeded implants. In conclusion, cell-based bone tissue
      engineering in an ectopic environment was clearly effective. Similar constructs
      implanted in a posterolateral spine fusion location hardly showed any effect.

PMID- 19769526
TI  - Bioprinted nanoparticles for tissue engineering applications.
AB  - Tissue engineering may require precise patterning and monitoring of cells and
      bioactive factors within the scaffold. We investigated a new hybrid
      nanobioprinting technique that facilitates manipulation and tracking of cells and
      bioactive factors within a three-dimensional tissue construct. This technique
      combines the initial patterning capabilities of syringe-based cell deposition
      with the active patterning capabilities of superparamagnetic nanoparticles.
      Superparamagnetic iron oxide nanoparticles, either in the alginate biopolymer or
      loaded inside endothelial cells, were bioprinted using a solid freeform
      fabrication direct cell writing system. Bioprinting did not impact cell viability
      when nanoparticles were in the alginate. However, both control and printed
      samples with 0.1 or 1.0 mg/mL nanoparticles in the alginate showed a 16% or 35%
      viability loss at 36 h after printing, respectively. Nanoparticle loading in
      cells decreased cell viability to 11% and bioprinting decreased viability to an
      additional 29% at 36 h. No changes were observed in any samples after 36 h,
      suggesting that cell viability stabilized following the initial nanoparticle
      toxicity effect. Nanoparticles in the alginate and those loaded in cells were
      moved using an external magnet, depending on biopolymer viscosity, and imaged by
      microcomputed tomography. The hybrid nanobioprinting method can noninvasively
      manipulate and track bioactive factors and cells within tissue engineering
      structures.

PMID- 19769528
TI  - Thermosensitive chitosan-gelatin-glycerol phosphate hydrogels as a cell carrier
      for nucleus pulposus regeneration: an in vitro study.
AB  - Injectable hydrogel is one of the great interests for tissue engineering and cell
      encapsulation. In the study, the gelatin molecules were added to the
      thermosensitive chitosan/beta-glycerol phosphate (C/GP) disodium salt hydrogels
      to form chitosan/gelatin/beta-glycerol phosphate (C/G/GP) disodium salt hydrogels
      which were applied as a cell carrier for nucleus pulposus (NP) regeneration. The
      gelation temperature, gelation time, and gel strength of the C/G/GP hydrogels
      were analyzed by the rheometer. NP cells were then harvested from the
      intervertebral discs of the adult New Zealand white rabbits and cultured in
      monolayer or in C/G/GP hydrogel, respectively. The cell viability, material
      mediated cytotoxicity, cell proliferation, production of sulfated
      glycosaminoglycans, anabolic/catabolic gene expressions, and extracellular matrix
      related gene expressions of the NP cells were demonstrated. The results show that
      the sol/gel transition temperature of the C/G/GP hydrogel was in the range of
      31.1-33.8 degrees C at neutral pH value, the gelation time was shortened, and the
      gel strength also improved at body temperature when compared with the C/GP
      hydrogel. Among those, C/GP with 1% gelatin addition showed the most promising
      gelation time and gel strength and were utilized in the later experiments. From
      the results of cell activity, cytotoxicity, and cell proliferation assays, NP
      cells cultured in C/G/GP hydrogel had normal cell viability and cell
      proliferation that indicated the hydrogel was noncytotoxicity. The amounts of
      sulfated glycosaminoglycans of NP cells cultured in C/G/GP hydrogels were
      significantly higher than monolayer cultured. Considering the extracellular
      matrix-related gene expression, type II collagen and aggrecan of NP cells
      cultured in the hydrogels greatly increased than those in monolayer culture. On
      the contrary, the unfavorable gene expression, such as that of type I collagen,
      was decreased significantly. The results reveal that gelatin added into C/GP
      hydrogel significantly shortened the gelation time and improved the gel strength
      without influencing the biocompatibility. NP cells cultured in the C/G/GP
      hydrogel also displayed better gene expressions when compared with the monolayer
      culture. This study indicates that using chitosan/gelatin hydrogel for NP cell
      culture is feasible and may apply in minimal invasive intervertebral disc surgery
      in the future.

PMID- 19769529
TI  - Engineering a titanium and polycaprolactone construct for a biocompatible
      interface between the body and artificial limb.
AB  - Intraosseous transcutaneous amputation prostheses may be able to overcome the
      problems that stem from the nonuniform distribution of pressure seen in the
      conventional stump-socket prosthetic replacement devices. Transcutaneous devices
      have had limited success in amputees. By optimizing the attachment of the skin to
      the prosthetic, intraosseous transcutaneous amputation prostheses may become
      clinically viable options. This report details studies evaluating the development
      of a modified titanium construct with a specially machined surface to increase
      the adherence of tissue as well as scaffold. A computer-aided biology tool was
      used to fabricate polycaprolactone (PCL) scaffolds with a specific three
      dimensional architecture. To extrude the PCL, it was dissolved in acetic acid to
      produce a 70% PCL liquid. A scaffold with a porosity of >50% was fabricated to
      have a tensile strength similar to skin. The presence of a specially machined
      surface greatly increased the adhesion of the PCL scaffold to the titanium
      constructs. When the 70% PCL was properly neutralized by heating at 55 degrees C
      and washing in 90% ethanol (EtOH), there was only a decrease (10%) in the
      viability of cells seeded onto the PCL constructs when compared with the cells in
      culture. The antibacterial properties of titanium dioxide anatase, silver
      nanoparticles, and chlorhexidine diacetate mixed in either type I collagen or
      hyaluronic acid (HA) were assessed. The addition of 1% (w/w) chlorhexidine
      diacetate in HA resulted in a 71% decrease in bacteria seen in nontreated HA.
      These results show promise in developing a novel engineered titanium and PCL
      construct that promotes effective adhesion between the titanium-skin interface.

PMID- 19769530
TI  - Transforming growth factor beta1 induces osteogenic differentiation of murine
      bone marrow stromal cells.
AB  - Bone marrow stromal cells (BMSCs) have been shown to contribute to regeneration
      of numerous mesodermal tissue types including adipose, bone, and cartilage.
      Recent studies have shown that BMSCs migrate into damaged bone and help
      facilitate effects such as fracture healing. Although bone morphogenic proteins
      have been shown to stimulate bone repair, their levels remain low postfracture.
      Peripheral blood levels of transforming growth factor beta1 (TGF-beta1), on the
      other hand, rise dramatically within 2 weeks postfracture. Therefore, we
      investigated the role of TGF-beta1 on BMSC osteogenic differentiation in vitro.
      Murine BMSCs were freshly isolated from femurs, fluorescence-activated cell
      sorted for Sca-1, cultured in Iscove's modified Dulbecco's medium, and exposed to
      TGF-beta1. After 14 days, real-time reverse transcriptase-polymerase chain
      reaction and immunohistochemical staining were performed to examine the
      expression of self-renewal and terminal differentiation markers. Results showed
      that the treatment with TGF-beta1 reduced mRNA levels of self-renewal markers
      (Oct4, Stella, Nanos3, and Abcg2) by twofold and increased osteoblast
      differentiation markers (Runx2, Opn, and Col1) up to sevenfold compared with
      controls. We also observed decreased mRNA levels of adipogenic markers (Pparg2
      and Adn) and an increase in alkaline phosphatase activity. Transcriptional
      coactivator with PDZ-binding motif (TAZ) mRNA and protein levels were elevated up
      to threefold following TGF-beta1 stimulation. In conclusion, our findings
      revealed an unexpected osteogenic differentiation pathway in murine BMSCs under
      the control of TGF-beta that is mediated by TAZ, which is known to increase RUNX2
      dependent gene transcription while repressing PPARgamma2-dependent transcription.
      This is the first report demonstrating the upregulation of TAZ activity in BMSCs
      by a physiological growth factor present during acute bone injury.

PMID- 19769532
TI  - Preparation and passive target of 5-fluorouracil solid lipid nanoparticles.
AB  - This work studied the intravenous injection formulation of solid lipid
      nanoparticles (SLNs) loaded with 5-fluorouracil (5-FU). The goal was to design
      longer drug residence in vivo and passive targeting nanoparticles which could
      improve therapeutic efficacy and reduce side-effects. Based on the optimized
      results of uniform design experiment, 5-FU-SLNs were prepared by multiple
      emulsion-ultrasonication (w/o/w). The SLNs were found to be relatively uniform in
      size (182.1 +/- 25.8 nm) with a negative zeta potential (-27.89 +/- 5.1 mV). The
      average drug entrapment efficiency and loading were 74% and 10%, respectively.
      Compared with the 5-FU solution (t(1/2beta), 0.593h; MRT, 0.358h) after
      intravenous injection to rats, the pharmacokinetic parameters of 5-FU-SLNs
      exhibited a longer retention time. (t(1/2beta), 4.0628h; MRT, 3.5321h). The area
      under curve of plasma concentration-time (AUC) of 5-FU-SLNs was 1.48 times
      greater than that of free drugs. The overall targeting efficiency (TE(C)) of the
      5-FU-SLNs was enhanced from 13.25-20.45% in the lung and from 11.48-23.16% in
      kidney while the spleen distribution of 5-FU was significantly reduced as
      compared with that of the 5-FU solution. These results indicated that 5-FU-SLNs
      were promising passive targeting therapeutic agents for curing primary lung
      carcinoma.

PMID- 19769536
TI  - Azithromycin plus artesunate versus artemether-lumefantrine for treatment of
      uncomplicated malaria in Tanzanian children: a randomized, controlled trial.
AB  - BACKGROUND: Acute febrile illness is the most common cause of outpatient
      attendance and mortality for children in Africa. Malaria and bacterial disease
      are difficult to differentiate with limited diagnostic facilities. Combinations
      of antibiotics and antimalarials are potentially attractive for treatment of the
      syndrome. Azithromycin plus artesunate (AT+AS) is an effective antimalarial
      combination for adults in Asia. METHODS: We performed an individually randomized,
      open-label trial of AZ+AS versus artemether-lumefantrine (AL) involving children
      (age, 6-59 months) with uncomplicated malaria in Muheza, Tanzania. The primary
      outcome was parasitological failure by day 28. Parasitological failure by day 42
      and failure corrected for reinfection were major secondary outcomes. RESULTS: Of
      2497 children screened, 261 were eligible; 129 were randomized to the AZ+AS arm,
      and 132 were randomized to the AL arm; 92% and 91%, respectively, underwent
      follow-up to 28 days. Planned interim analysis was performed after 200 patients
      reached day 28 follow-up and led the Data and Safety Monitoring Board to halt
      further recruitment. All children had a complete initial response to treatment,
      but 69 (58%) of 119 children in the AZ+AS arm and 24 (20%) of 120 in the AL arm
      had asexual parasites at or by day 28 (adjusted odds ratio for failure with AZ+AS
      treatment, 6.1; 95% confidence interval, 3.3-11.4; P < .001). When analysis was
      restricted to children with recrudescence, the parasitological failure rate was
      32% in the AZ+AS arm and 9% in the AL arm. This difference was maintained at day
      42. CONCLUSIONS: This trial does not support the use of AZ+AS as treatment for
      malaria or acute febrile illness in children in areas of Africa with high levels
      of existing antimalarial drug resistance. CLINICAL TRIALS REGISTRATION:
      ClinicalTrials.gov NCT00694694.

PMID- 19769537
TI  - Why does size matter? A test of the benefits of female mate choice in a teleost
      fish based on morphological and physiological indicators of male quality.
AB  - In female mate choice, a female chooses a reproductive partner based on direct or
      indirect benefits to the female. While sexual selection theory regarding female
      mate choice is well developed, there are few mechanistic studies of the process
      by which females evaluate reproductive partners. Using paternal-care-providing
      smallmouth bass (Micropterus dolomieu) as a model, the purpose of this study was
      to determine the relationship between female mate choice and the morphological
      and physiological status of chosen males. This was accomplished by locating nests
      within 1 d of spawning and categorizing brood size (indicator of female mate
      choice). This was followed by capture of parental males, which were blood sampled
      (for nutritional analyses), digitally photographed (for morphometric analyses),
      and released. Principal components analysis (PCA) of morphometric measurements
      described 72.7% of the variance associated with body morphology and generated
      three principal components (PCs) indicative of fusiform body shape, increased
      posterior size, and body stoutness. PCA of nutritional indicators described 75.4%
      of the variance associated with physiological metrics and generated two PCs
      indicative of plasma mineral content (Ca(++) and Mg(+)) and energetic condition
      (total protein, triglyceride, and cholesterol). Male total length and body
      stoutness were the only significant predictors of female mate choice.
      Interestingly, no nutritional indicators were predictive of female mate choice,
      and there were no direct relationships between morphological variables and
      nutritional physiology indicators. Further research is needed to elucidate the
      mechanistic relationships between morphology and nutritional physiology
      (especially in relation to the parental-care period) of individual fish to
      determine the basis of female mate preference.

PMID- 19769538
TI  - Development of reduced vancomycin susceptibility in methicillin-susceptible
      Staphylococcus aureus.
AB  - BACKGROUND: Most cases of reduced vancomycin susceptibility in Staphylococcus
      aureus reported in the literature have been in methicillin-resistant strains. We
      report the development of reduced vancomycin susceptibility in a series of
      clonally related, methicillin-susceptible S. aureus (MSSA) clinical isolates.
      This isogenic series permitted us to determine whether the evolution of reduced
      vancomycin susceptibility in MSSA is similar to that seen in MRSA. METHODS:
      Differences in vancomycin population analysis profiles; chemical autolysis;
      vancomycin, oxacillin, and daptomycin minimum inhibitory concentrations; and
      bactericidal activities were examined. RESULTS: Progressive vancomycin resistance
      correlated with increasing daptomycin nonsusceptibility. Chemical autolysis and
      the bactericidal activity of vancomycin, oxacillin, and daptomycin were reduced
      in the final, vancomycin-intermediate S. aureus isolate, compared with the
      vancomycin-susceptible MSSA progenitor. CONCLUSIONS: Clinicians should recognize
      that reduced vancomycin susceptibility can occur in S. aureus irrespective of
      background methicillin susceptibility and that development of intermediate
      vancomycin susceptibility in MSSA may result in increased tolerance to several
      classes of anti-staphylococcal antibiotics.

PMID- 19769539
TI  - Infections in patients with multiple myeloma in the era of high-dose therapy and
      novel agents.
AB  - The introduction of stem cell transplantation and the novel anti-myeloma agents,
      bortezomib, thalidomide, and lenalidomide, have improved the outcome of patients
      with multiple myeloma. These advances have transformed myeloma into a chronic
      condition, with multiple relapses and salvage therapies, all of which result in
      cumulative immunosuppression and higher risk of infection. In addition to the
      immunodeficiency related to myeloma and its complications, the type of anti
      myeloma therapy used also plays a role in the development of infection. Therapy
      with bortezomib increases the risk for reactivation of herpes simplex and herpes
      zoster viruses, whereas the application of stem cell transplantation has
      broadened the spectrum of infection to include those caused by Clostridium
      difficile, cytomegalovirus, and opportunistic moulds. Key to the management of
      infection is the understanding of the specific risk factors and periods during
      which patients are at risk; this allows the anticipation of the likely
      pathogen(s) and the application of risk-adjusted prophylactic and treatment
      strategies.

PMID- 19769540
TI  - Transkingdom RNA interference (tkRNAi) as a new delivery tool for therapeutic
      RNA.
AB  - RNA interference (RNAi) represents a powerful mechanism for the knockdown of any
      target gene of interest. It is based on the action of small double-stranded RNA
      molecules (siRNAs) which are complementary to the target sequence. Crucial for
      the induction of RNAi, particularly for any therapeutic in vivo applications, is
      the delivery of siRNAs or small hairpin RNA (shRNA)-encoding DNA constructs.
      Extending the portfolio of viral or non-viral strategies, bacteria have been
      shown to be able to deliver shRNA-encoding DNA into tumor cells. In a process
      termed 'transkingdom RNA interference' (tkRNAi), the genetically modified
      bacteria themselves produce shRNAs which, upon bacterial infection, become
      available for the target cells for further processing and induction of RNAi. In
      'bacteria-mediated RNAi' (bm-RNAi), the bacteria only deliver the shRNA-encoding
      DNA construct with subsequent transcription of the shRNA in the target cells.
      This review briefly discusses general aspects of the RNAi mechanism and various
      delivery systems, and then describes tkRNAi and bm-RNAi in the context of
      therapeutic applications.

PMID- 19769542
TI  - The Journal Impact Factor: don't expect its demise any time soon.
AB  - Much emphasis continues to be placed on the Journal Impact Factor (IF), a measure
      of journal article citation rates, and typically used as a surrogate marker of
      quality of both the article and journal. The IF is both revered and reviled, and
      is neither a perfect nor comprehensive measure, having several limitations and
      being subject to easy manipulation. The IF holds 'power' for journals because it
      can influence their future success. Furthermore, the perceived utility of the IF
      has grown way beyond that of its original and still popular use as a surrogate
      marker of publication 'quality'. The IF is increasingly being used (i) to
      objectively evaluate the scientific and academic value of scientists across a
      wide variety of disciplines, (ii) to short-list research projects for future
      financial support, (iii) to short-list or select applicants for academic
      promotion, and (iv) by researchers to measure the success of research institutes,
      research funding, or even entire countries. Accordingly, despite our love-hate
      relationship with the IF, don't expect its demise any time soon.

PMID- 19769541
TI  - Anthrax prevention and treatment: utility of therapy combining antibiotic plus
      vaccine.
AB  - The intentional release of anthrax spores in 2001 confirmed this pathogen's
      ability to cause widespread panic, morbidity and mortality. While individuals
      exposed to anthrax can be successfully treated with antibiotics, pre-exposure
      vaccination can reduce susceptibility to infection-induced illness. Concern over
      the safety and immunogenicity of the licensed US vaccine (Anthrax Vaccine
      Adsorbed (AVA)) has fueled research into alternatives. Second-generation anthrax
      vaccines based on purified recombinant protective antigen (rPA) have entered
      clinical trials. These rPA vaccines induce neutralizing antibodies that prevent
      illness, but the magnitude and duration of the resultant protective response is
      modest. Efforts are underway to bolster the immunogenicity of rPA by combining it
      with adjuvants and other immunostimulatory agents. Third generation vaccines are
      under development that utilize a wide variety of immunization platforms,
      antigens, adjuvants, delivery methods and routes of delivery to optimize the
      induction of a protective immunity. For the foreseeable future, vaccination will
      rely on first and second generation vaccines co-administered with immune
      adjuvants. Optimal post-exposure treatment of immunologically naive individuals
      should include a combination of vaccine plus antibiotic therapy.

PMID- 19769543
TI  - Prevalence of thyroid autoimmunity and subclinical hypothyroidism in persons with
      chronic kidney disease not requiring chronic dialysis.
AB  - BACKGROUND: The prevalence of thyroid autoimmunity and subclinical primary
      hypothyroidism in persons with chronic kidney disease (CKD) not requiring chronic
      dialysis is not well defined. METHODS: We studied 1000 consecutive adult
      outpatients who were referred by their general practitioner for blood testing
      over the last 2 years. We excluded those with abnormal serum free thyroxine (FT4)
      levels (n=85). No participants required chronic renal replacement therapy.
      Thyroid autoimmunity was defined as increased concentrations of serum anti
      thyroid antibodies. Subclinical primary hypothyroidism was defined as a serum
      thyrotropin (TSH) concentration >4 mIU/L. CKD was defined as an estimated
      glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2). RESULTS: Overall, 53
      (5.8%) subjects had eGFR <60 mL/min/1.73 m(2). Of these, 98 (10.7%) had
      subclinical hypothyroidism, and 213 (23.3%) subjects had increased anti-thyroid
      antibodies. Approximately 26% and 34% of those with eGFR <60 mL/min/1.73 m(2) had
      laboratory evidence of subclinical hypothyroidism or thyroid autoimmunity,
      respectively. In subgroup analysis stratified by TSH and thyroid autoimmunity,
      decreasing eGFR values appeared to be more strongly related with the increase in
      TSH rather than antithyroid antibodies. CONCLUSIONS: Thyroid autoimmunity and
      subclinical primary hypothyroidism are highly prevalent in persons with CKD not
      requiring chronic dialysis.

PMID- 19769544
TI  - Stimulation of sigma-1 receptor signaling by dehydroepiandrosterone ameliorates
      pressure overload-induced hypertrophy and dysfunctions in ovariectomized rats.
AB  - OBJECTIVE: Decreased dehydroepiandrosterone (DHEA) levels are associated with
      endothelial dysfunction and increased cardiovascular mortality in postmenopausal
      women. We investigated the role of DHEA, also known as sigma-1 receptor (Sig-1R)
      agonist, in myocardial hypertrophy, cardiac functional recovery and defined
      mechanisms of cardioprotective action. METHODS: Wistar rats subjected to
      bilateral ovariectomy (OVX) were further treated with abdominal aortic stenosis.
      DHEA (15 and 30 mg/kg) was administered orally once a day for 14 days starting
      from 2 weeks after aortic banding. RESULTS: Time course study indicated that left
      ventricle (LV) weight:body weight (BW) ratio increased time-dependently from 1 to
      4 weeks after pressure-overload (PO) with significant inversed regulation of Sig
      1R expression. Treatment with the Sig-1R agonist, DHEA, significantly attenuated
      PO-induced myocardial hypertrophy with increased expression of Sig-1R in the LV.
      DHEA also attenuated hypertrophy-induced impaired LV end diastolic pressure, LV
      developed pressure and LV contractility (+/- dp/dt(max)). DHEA treatment
      significantly restored PO-induced impaired eNOS and Akt activity in the LV.
      CONCLUSION: We report, for the first time to our knowledge, the potential role of
      Sig-1R expression in the heart to attenuate PO-induced hypertrophy in
      ovariectomized rats. DHEA treatment protects against PO-induced cardiac injury
      via upregulation of Sig-1R and stimulation of Sig-1R-mediated Akt-eNOS signaling.

PMID- 19769546
TI  - Targeting the EGF receptor ectodomain in the context of cancer.
AB  - With the discovery of the involvement of the ErbB family of transmembrane growth
      factor receptors in tumour malignancy, major efforts have been undertaken to
      develop agents able to specifically target these receptors. With varying success,
      these agents have been applied to either detect the presence of ErbB receptors on
      cancer cells or to neutralize receptor function in order to put a hold on the
      unbridled tumour growth. The two most exploited classes of ErbB-targeting agents
      are monoclonal antibodies binding the extracellular portion of the receptor and
      small molecules able to interfere with the intracellular tyrosine kinase
      activity. Here we focus on the various kinds of agents that have recently been
      developed to target the extracellular region of the EGFR, the best characterised
      member of the ErbB family. Because clinical successes are relatively poor,
      alternative but less developed approaches for receptor targeting are being
      evaluated. Much effort has been put into the development of smaller antibody
      fragments. In this context, EGFR-binding nanobodies and affibodies may prove to
      be a more efficient novel approach in targeting EGFR-positive tumours for
      therapeutic and diagnostic use.

PMID- 19769547
TI  - Arachidonic acid and calcium signals in human breast tumor-derived endothelial
      cells: a proteomic study.
AB  - Intracellular calcium signals activated by growth factors in endothelial cells
      during angiogenesis regulate cytosolic and nuclear events involved in survival,
      proliferation and motility. Among the intracellular messengers released upon
      proangiogenic stimulation, arachidonic acid (AA) and its metabolites play a key
      role, and their effects are strictly related to calcium homeostasis. In human
      breast tumor-derived endothelial cells (B-TECs) AA stimulates proliferation and
      tubulogenesis in a calcium-dependent way. Here, to characterize the proteins
      whose expression is regulated by AA-induced calcium entry, we used a proteomic
      approach (two-dimensional gel electrophoresis and matrix-assisted laser
      desorption ionization mass spectrometry, 2-DE and MALDI-MS) and we compared the
      proteomes of B-TECs stimulated with AA in presence or in absence of calcium entry
      (with addition to the culture medium of the calcium chelator EGTA, which
      completely prevents calcium fluxes throughout the plasma membrane). We found that
      six proteins increased their levels of expression, all higher when AA-induced
      calcium entry was abolished. These proteins have been identified by mass
      spectrometry and database search, and their potential roles in AA-stimulated
      pathway and in angiogenesis are discussed.

PMID- 19769548
TI  - Cost-effectiveness of quetiapine with lithium or divalproex for maintenance
      treatment of bipolar I disorder.
AB  - BACKGROUND: Bipolar I disorder is a recurrent illness that affects 1% of the US
      population and constitutes a large economic burden. Few studies have investigated
      the cost-effectiveness of maintenance treatment options. The objective of this
      analysis was to assess the cost-effectiveness of quetiapine (QTP) in combination
      with lithium (Li) or divalproex (DVP) compared with that of Li or DVP alone for
      maintenance treatment of bipolar disorder. METHODS: The cost-effectiveness of
      maintenance treatment with QTP in combination with Li or DVP was compared with
      placebo (PBO) in combination with Li or DVP from a US direct costs perspective
      using a Markov model. The model simulated a cohort of 1,000 stabilized patients
      with bipolar I disorder and estimated the quarterly risk in three health states:
      euthymia, mania, and depression. Efficacy data were derived from two randomized,
      double-blind, placebo-controlled trials comparing QTP + Li/DVP with PBO + Li/DVP
      for up to 2 years. Resource data were obtained from published literature. Direct
      costs included drug costs, hospitalizations, and physician visits. Outcomes and
      costs were discounted at 3% and the price reference year was 2007. Endpoints
      included the number of acute mood episodes, hospitalizations due to an acute mood
      event, and costs per quality-adjusted life-years. A probabilistic sensitivity
      analysis (PSA) was conducted to evaluate uncertainty. RESULTS: In the base-case
      analysis, QTP + Li/DVP dominated PBO + Li/DVP. The PSA showed these results to be
      robust. In addition, treatment with QTP + Li/DVP was associated with reductions
      in acute manic episodes (46%), acute depressive episodes (41%), and related
      hospitalizations (44%) compared with PBO + Li/DVP. CONCLUSIONS: These analyses,
      based on two randomized clinical trials, suggest that QTP + Li/DVP is a cost
      effective maintenance treatment option for patients with bipolar I disorder
      compared with Li or DVP alone.

PMID- 19769549
TI  - Maximising the effectiveness and cost-effectiveness of cardiovascular disease
      prevention in the general population.

PMID- 19769545
TI  - Targeting the A2B adenosine receptor during gastrointestinal ischemia and
      inflammation.
AB  - Extracellular adenosine functions as an endogenous distress signal via activation
      of four distinct adenosine receptors (A1, A2A, A2B and A3). Conditions of limited
      oxygen availability or acute inflammation lead to elevated levels of
      extracellular adenosine and enhanced signaling events. This relates to a
      combination of four mechanisms: i) increased production of adenosine via
      extracellular phosphohydrolysis of precursor molecules (particularly ATP and
      ADP); ii) increased expression and signaling via hypoxia-induced adenosine
      receptors, particularly the A2B adenosine receptor; iii) attenuated uptake from
      the extracellular towards the intracellular compartment; and iv) attenuated
      intracellular metabolism. Due to their large surface area, mucosal organs are
      particularly prone to hypoxia and ischemia associated inflammation. Therefore, it
      is not surprising that adenosine production and signaling plays a central role in
      attenuating tissue inflammation and injury during intestinal ischemia or
      inflammation. In fact, recent studies combining pharmacological and genetic
      approaches demonstrated that adenosine signaling via the A2B adenosine receptor
      dampens mucosal inflammation and tissue injury during intestinal ischemia or
      experimental colitis. This review outlines basic principles of extracellular
      adenosine production, signaling, uptake and metabolism. In addition, we discuss
      the role of this pathway in dampening hypoxia-elicited inflammation, specifically
      in the setting of intestinal ischemia and inflammation.

PMID- 19769550
TI  - Improving the management of chronic non-malignant pain and reducing problems
      associated with prescription opioids.
AB  - New guidelines and a multidisciplinary approach have the potential to help
      patients in need while minimising inappropriate use of opioids.

PMID- 19769551
TI  - Cardiovascular disease risk management for Aboriginal and Torres Strait Islander
      peoples in primary health care settings: findings from the Kanyini Audit.
AB  - OBJECTIVE: To describe cardiovascular disease (CVD) risk management in Indigenous
      primary health care. DESIGN, SETTING AND PARTICIPANTS: Review of 1165 randomly
      selected case records of Indigenous Australian adults, aged >/= 18 years,
      regularly attending eight health services in diverse settings in New South Wales,
      Queensland and Central Australia, October 2007 - May 2008. MAIN OUTCOME MEASURE:
      Adherence to CVD risk screening and management guidelines, especially with
      respect to overall or absolute CVD risk. RESULTS: More than half the people in
      the sample (53%) were not adequately screened for CVD risk according to national
      recommendations. Underscreening was significantly associated with younger age,
      less frequent attendance, and lower uptake of the Medicare Health Assessment. Of
      the sample, 9% had established CVD, and 29% of those aged >/= 30 years were
      classified as high risk according to the 2004 National Heart Foundation of
      Australia (NHFA) adjusted Framingham equation. Of those with CVD, 40% (95% CI,
      30%-50%) were not prescribed a combination of blood pressure (BP) medicines,
      statins and antiplatelet agents, and 56% (95% CI, 49%-62%) of high-risk
      individuals without CVD were not prescribed BP medicines and statins. For high
      risk individuals not prescribed BP medicines or statins, 74% (95% CI, 64%-84%)
      and 30% (95% CI, 23%-39%) respectively, did not meet 2004 NHFA criteria for
      prescribing of these medications, and of those already prescribed BP medicines or
      statins, 41% (95% CI, 36%-47%) and 59% (95% CI, 52%-66%) did not meet respective
      guideline targets. CONCLUSIONS: These management gaps are similar to those found
      in non-Indigenous health care settings, suggesting deficiencies across the health
      system. Prescribing guidelines which exclude many high-risk individuals
      contribute to suboptimal management. Guideline reform and improved health service
      capacity could substantially improve Indigenous vascular health.

PMID- 19769552
TI  - Adenocarcinoma of the oesophagus: incidence and survival rates in New South
      Wales, 1972-2005.
AB  - OBJECTIVE: To investigate trends in the incidence of adenocarcinoma (AC) of the
      oesophagus in New South Wales, factors associated with a diagnosis of AC, and
      factors associated with survival of patients with AC. DESIGN AND SETTING: We
      examined all cases of invasive oesophageal cancer recorded in the NSW Central
      Cancer Registry from 1972 to 2005. The Accessibility/Remoteness Index of
      Australia was used to assess geographical remoteness and the Index of Relative
      Socio-Economic Disadvantage to assess socioeconomic status. MAIN OUTCOME
      MEASURES: Incidence of AC; factors associated with diagnosis of AC and survival
      of patients with AC. RESULTS: The overall incidence of oesophageal AC in NSW
      increased in both males and females (annual percentage change, 4.2% [95% CL,
      2.7%, 5.8%] in males [1988-2005] and 4.3% [95% CL, 1.8%, 7.0%] in females [1983
      2005]). A diagnosis of AC was significantly associated with being male (adjusted
      odds ratio [AOR], 4.37 [95% CL, 3.84, 4.98]; P < 0.001); a younger age at
      diagnosis (P trend < 0.001); having distant rather than localised disease spread
      (AOR, 2.12 [95% CL, 1.82, 2.48]; P < 0.001); higher socioeconomic status (P trend
      < 0.001); and living in an inner regional area (AOR, 1.26 [95% CL, 1.11, 1.43]; P
      < 0.001) or outer regional area (AOR, 1.19 [95% CL, 1.00, 1.41]; P = 0.05)
      compared with a major city. Early diagnosis of AC was associated with substantial
      improvement in survival outcomes: patients with metastatic disease at diagnosis
      had a three times greater risk of dying than those with localised AC at
      diagnosis. CONCLUSION: The incidence of AC is increasing in NSW. Possible
      contributing factors include increasing obesity, which is associated with
      increased incidence of gastro-oesophageal reflux disease. Survival may be
      improved by diagnosis at an earlier stage and changes in modifiable risk factors
      (eg, smoking, diet, exercise).

PMID- 19769553
TI  - Multidrug-resistant tuberculosis in Victoria: a 10-year review.
AB  - OBJECTIVE: To describe demographic and clinical characteristics of patients
      residing in Victoria who were diagnosed with multidrug-resistant tuberculosis
      (MDR-TB) during the period 1 January 1998 to 31 December 2007. DESIGN, SETTING
      AND PATIENTS: Retrospective review of Victorian Department of Health data on
      laboratory-confirmed cases of MDR-TB for the period 1998-2007. MAIN OUTCOME
      MEASURES: Age, sex, country of birth, time between arrival in Australia and
      notification of TB, residency status, site of disease, and treatment period and
      outcome. RESULTS: From 1998 to 2007, 31 patients who resided in Victoria were
      diagnosed with MDR-TB. The median age of patients was 27 years, most patients
      were born overseas, and more than half were full-time students. The median time
      between arrival in Australia and notification of TB was 2 years, and 24 patients
      were notified to the Department within 5 years of arrival. Twenty patients had
      pulmonary disease; in 12 of these patients, sputum was smear-positive for acid
      fast bacilli. The median treatment period for patients who completed treatment
      was 22 months. CONCLUSIONS: The number of patients diagnosed with MDR-TB per year
      increased during the period 1998-2007. If sustained, this increase will have
      important implications for public health policy and planning.

PMID- 19769554
TI  - Cost is a major barrier to the use of inhaled corticosteroids for obstructive
      lung disease.
AB  - OBJECTIVE: To examine the effect of the level of patient copayment on the rate of
      purchase of inhaled corticosteroids (ICS) by patients with obstructive lung
      disease. DESIGN AND SETTING: Cross-sectional study of records of all
      prescriptions for ICS dispensed to general and concessional beneficiaries aged 15
      years or over in the period January 2003 to December 2006. Data were obtained
      from the Pharmaceutical Benefits Scheme, which subsidises medication costs for
      all Australians. MAIN OUTCOME MEASURES: The number of prescriptions for ICS
      dispensed to government concession card holders compared with the number
      dispensed to general beneficiaries, expressed as a rate ratio. RESULTS: ICS
      prescriptions were dispensed to over 1.6 million people during the study period.
      Concession card holders were dispensed ICS prescriptions at a higher rate than
      general beneficiaries, both overall (43.7 v 9.1 ICS prescriptions per 100 person
      years) and in all population subgroups. After adjusting for age, sex, remoteness
      category and socioeconomic status, people holding a concession card were
      dispensed over 2.5 times the number of ICS prescriptions (alone or in combination
      with a long-acting beta(2)-agonist) compared with general beneficiaries. Similar
      patterns were seen after adjusting for differences between the two groups in the
      prevalence of obstructive lung disease. CONCLUSIONS: As the patient copayment for
      general beneficiaries is over six times higher than for concession card holders,
      our findings imply that cost is a barrier to the purchase of ICS prescriptions
      for obstructive lung disease, independent of socioeconomic status.

PMID- 19769555
TI  - Gaps in cardiovascular disease risk management in Australian general practice.
AB  - OBJECTIVE: To evaluate the management of cardiovascular disease (CVD) risk in
      Australian general practice. DESIGN, SETTING AND PARTICIPANTS: National cross
      sectional survey of 99 Australian general practitioners participating in the
      Bettering the Evaluation and Care of Health (BEACH) program. Data on 2618
      consecutive adult patients presenting to the participating GPs over a 5-week
      period from September to October 2006 were analysed. MAIN OUTCOME MEASURES:
      Proportions of patients screened, treated and reaching targets according to (1)
      current Australian CVD risk guidelines and (2) overall or absolute CVD risk.
      RESULTS: Blood pressure (BP) had not been recorded for 13% of the sample. Of 1400
      patients not prescribed antihypertensive medication, treatment was indicated for
      8%. Of 821 patients already prescribed antihypertensive medication, 59% were
      achieving target BPs. Data on low-density lipoprotein (LDL) cholesterol levels
      were not available for 53% of the 2175 patients who should have had lipid
      screening according to the guidelines. Of 624 patients not prescribed a statin,
      treatment was indicated for 41%. Of 368 already prescribed a statin, 62% were
      achieving target LDL cholesterol levels. Sufficient data for calculation of
      absolute risk had been recorded for 74% of the 1736 patients for whom such
      calculation was recommended by the guidelines. The remaining 26% either had at
      least one required variable unmeasured (20%) or missing from the data collection
      (6%). For those at high absolute CVD risk (without established disease) and those
      with established CVD, 23% and 53%, respectively, had been prescribed both
      antihypertensive medication and a statin. CONCLUSIONS: Gaps between guideline
      recommendations and practice in recording and managing BP were relatively low
      compared with gaps for lipids. When stratified by absolute risk, patients at high
      risk of a cardiovascular event were found to be substantially undertreated.

PMID- 19769556
TI  - A pilot study of trimodality breast imaging surveillance in young women at high
      risk of breast cancer in Western Australia.
AB  - OBJECTIVE: To determine whether a surveillance program including clinical breast
      examination (CBE) and three screening modalities (magnetic resonance imaging
      [MRI], high-resolution ultrasound [U/S] and mammographic x-ray [MMX]) was
      feasible, and whether it could improve detection of pathological lesions in young
      women at high risk of developing breast cancer. DESIGN, SETTING AND PARTICIPANTS:
      Western Australian women aged 50 years or under at high risk of developing breast
      cancer were recruited to our study. For a 2-year period, they were offered breast
      MRI and U/S scans in addition to their annual MMX and CBE. Our study was
      conducted between June 2002 and October 2005. MAIN OUTCOME MEASURES: Number and
      type of cancerous or precancerous lesions; recall rates after screening;
      comparative sensitivity of screening modalities. RESULTS: Of 102 women
      approached, 72 agreed to participate. Fifteen lesions were detected, of which
      three were significant: a metastatic papillary cancer in an axillary lymph node,
      a borderline lesion (multiple papillomatosis with atypia), and a papilloma. All
      15 lesions were visible on MRI, and four were detected by MRI only. Only one
      lesion was visible on all three imaging modalities. Nothing significant was
      detected by CBE. The recall rate after MRI scans fell from 9/72 (12.5%) in the
      first year to 5/67 (7.5%) in the second year. CONCLUSION: Our study gave valuable
      experience in a team approach to screening MRI, and showed that MRI can detect
      more lesions than MMX or U/S in women at high risk of developing breast cancer.
      Screening U/S may not add value to MMX and MRI screening, and we suggest a single
      oblique-view MMX may be used in some cases.

PMID- 19769557
TI  - Acute coronary syndromes: consensus recommendations for translating knowledge
      into action.
AB  - A systematic, integrated national approach is needed to implement 2006 Australian
      guidelines for management of acute coronary syndromes (ACS). Clinical outcomes
      can be improved by closing the current gaps between evidence and practice. In
      2007, the National Heart Foundation of Australia, the Cardiac Society of
      Australia and New Zealand, and the Australasian College for Emergency Medicine
      held a national forum to identify current gaps in ACS management and priority
      strategies to improve outcomes. Consensus recommendations were based on evidence
      and expert opinion. Prompt reperfusion for patients with ST-segment-elevation
      myocardial infarction should be ensured by establishing protocols for single-call
      activation of primary percutaneous coronary intervention, or, where unavailable,
      enabling health care workers to initiate thrombolysis. Accuracy of risk
      stratification of non-ST-segment-elevation ACS (NSTEACS) should be improved using
      clinical pathways that integrate ambulance, medical and nursing care. Rates of
      early invasive management for patients with high-risk NSTEACS should be increased
      using efficient systems for transfer to revascularisation facilities. All
      patients with an ACS should be referred to rehabilitation and secondary
      prevention programs, including alternative models of care where appropriate.
      Equal access to recommended care for all Australians with an ACS - including
      those in rural, remote and Aboriginal and Torres Strait Islander communities -
      should be achieved by improving workforce capacity in under-resourced regions and
      ensuring access to third-generation fibrinolytic agents, defibrillation, timely
      essential pathology tests and invasive revascularisation facilities. National
      standards for data collection and clinical outcomes should be established, and
      performance should be monitored.

PMID- 19769558
TI  - Position statement of the Australian Diabetes Society: individualisation of
      glycated haemoglobin targets for adults with diabetes mellitus.
AB  - Tight glycaemic control reduces the risk of development and progression of organ
      complications in people with type 1 or type 2 diabetes. In this position
      statement, the Australian Diabetes Society recommends a general target glycated
      haemoglobin (HbA(1c)) level of </= 7.0% for most patients. This position
      statement also provides guidelines for the individualisation of glycaemic targets
      to a tighter or lesser degree, with a recommended target HbA(1c) level of </=
      6.0% in some people, or up to </= 8.0% in others. Individualisation of the
      HbA(1c) target is based on patient-specific factors, such as the type of diabetes
      and its duration, pregnancy, diabetes medication being taken, presence of
      cardiovascular disease, risk of and problems from hypoglycaemia, and
      comorbidities. Management of diabetes also includes: adequate control of other
      cardiovascular risk factors, including weight, blood pressure and lipid serum
      levels; antiplatelet therapy; and smoking cessation.

PMID- 19769559
TI  - Our public health system: an accident waiting to happen?
AB  - Our public health system, addicted to increasing centralisation and regulation,
      is pushing our everyday work environment beyond the point of sustainability - it
      has become too complex. Like an ecosystem grown too complex to resist sudden
      environmental change, public health organisations have become "brittle", unable
      to respond to changing conditions. Another bureaucratic restructuring, such as
      recommended by the Garling report, can only be self-defeating. It is time for us
      to design systems small enough, and therefore resilient enough, to meet
      tomorrow's challenges.

PMID- 19769560
TI  - A case of discordant HbA(1c): a method-dependent error.
AB  - Although glycated haemoglobin (HbA(1c)) has become the key biochemical marker of
      long-term glycaemic control, analytical method-dependent differences in results
      can occur when haemoglobin variants are present or HbA(1c) is reduced by
      decreased red cell survival. When the measured HbA(1c) level is discordant with
      the patient's blood glucose measurements and clinical status, fructosamine is an
      alternative biochemical marker that can provide a more accurate estimate of the
      glycaemic control and enable clinicians to appropriately manage patients.

PMID- 19769561
TI  - Early use of high-dose insulin euglycaemic therapy for verapamil toxicity.
AB  - A 49-year-old man presented with verapamil toxicity complicated by hypotension
      and a junctional rhythm, in the context of deliberate self-poisoning with
      multiple drugs. The patient's hypotension normalised following the early use of
      high-dose insulin euglycaemic therapy (HIET), without the need for additional
      vasopressors; it recurred when HIET was prematurely stopped, and again stabilised
      when HIET was recommenced. Consideration should be given to the early use of HIET
      in treating severe calcium channel blocker toxicity, rather than as a last resort
      after other therapies have failed.

PMID- 19769562
TI  - Inappropriate prescribing for osteoporosis.

PMID- 19769563
TI  - Should aspirin be used for the primary prevention of cardiovascular disease in
      people with diabetes?

PMID- 19769564
TI  - Perinatal transmission of hepatitis B virus: an Australian experience.

PMID- 19769565
TI  - Quality of drug interaction alerts in prescribing and dispensing software.

PMID- 19769566
TI  - Pathology processes and emergency department length of stay: the impact of
      change.

PMID- 19769567
TI  - EIN2, the central regulator of ethylene signalling, is localized at the ER
      membrane where it interacts with the ethylene receptor ETR1.
AB  - Genetic studies have identified the membrane protein EIN2 (ethylene insensitive
      2) as a central component of ethylene signalling in Arabidopsis. In addition,
      EIN2 might take part in multiple hormone signalling pathways and in response to
      pathogens as demonstrated by recent genetic and biochemical studies. Here we
      show, by an integrated approach using in vivo and in vitro fluorescence
      techniques, that EIN2 is localized at the ER (endoplasmic reticulum) membrane
      where it shows specific interaction with the ethylene receptor protein ETR1.

PMID- 19769568
TI  - Leishmania donovani Ran-GTPase interacts at the nuclear rim with linker histone
      H1.
AB  - Ran-GTPase regulates multiple cellular processes such as nucleocytoplasmic
      transport, mitotic spindle assembly, nuclear envelope assembly, cell-cycle
      progression and the mitotic checkpoint. The leishmanial Ran protein, in contrast
      with its mammalian counterpart which is predominately nucleoplasmic, is localized
      at the nuclear rim. The aim of the present study was to characterize the LdRan
      (Leishmania donovani Ran) orthologue with an emphasis on the Ran-histone
      association. LdRan was found to be developmentally regulated, expressed 3-fold
      less in the amastigote stage. LdRan overexpression caused a growth defect linked
      to a delayed S-phase progression in promastigotes as for its mammalian
      counterpart. We report for the first time that Ran interacts with a linker
      histone, histone H1, in vitro and that the two proteins co-localize at the
      parasite nuclear rim. Interaction of Ran with core histones H3 and H4, creating
      in metazoans a chromosomal Ran-GTP gradient important for mitotic spindle
      assembly, is speculative in Leishmania spp., not only because this parasite
      undergoes a closed mitosis, but also because the main localization of LdRan is
      different from that of core histone H3. Interaction of Ran with the leishmanial
      linker histone H1 (LeishH1) suggests that this association maybe involved in
      modulation of pathways other than those documented for the metazoan Ran-core
      histone association.

PMID- 19769569
TI  - The lingual dorsal surface of the blue-tongue skink (Tiliqua scincoides).
AB  - The blue-tongue lizard (Tiliqua scincoides) is a variety of large skink common
      throughout Australia. There are seven species of Tiliqua and all of them have
      long bodies, short limbs and short and robust tails. T. scincoides occurs in a
      wide range of habitats; its diet is omnivorous. When threatened, it opens the
      mouth and protrudes its characteristic large fleshy cobalt blue tongue. It is
      currently found as a popular species and also as a pet animal in the European
      countries. No data are available in literature about the morphology of the tongue
      of T. scincoides; therefore, the aim of the present study was to investigate by
      means of scanning electron microscopy and light microscopy, the anatomy of the
      dorsal lingual surface. Our results demonstrate the presence of a tongue tip with
      a smooth surface without papillae. The foretongue was characterized by a
      stratified epithelium with foliate-like papillae and deep inter-papillar spaces
      in the middle part and cylindrical papillae with a flat surface in the lateral
      parts. All the posterior area of the tongue was characterized by more compacted
      papillae and the inter-papillar spaces were very narrow. Light microscopy showed
      the presence of melanin throughout the tongue. No taste buds were recognized on
      the lingual dorsal surface. Therefore, the papillae probably have a mechanical
      function showing an important role in the swallowing phase. The morphology of the
      tongue surface can be correlated to the diet and, different roles, as in other
      examined species, can be hypothesized for different areas.

PMID- 19769570
TI  - Active participation instead of passive behaviour opens up new vistas in
      education of veterinary anatomy and histology.
AB  - Teaching morphology, a fundamental part of medicine curricula is traditionally
      based on lectures and practical trainings. We introduced peer-assisted learning
      (PAL) and student expert teams to the courses to give the students the
      possibility to improve their free speech and self-confidence. We involved
      students in active preparation of online materials such as labelled e-slides and
      e-pics. We offered online digital microscopy (Zoomify) and dissection (CyberPrep)
      allowing repeating the learned material and studying veterinary morphology
      outside the dissection theatre. Over 60% of first and third semester students
      profited from being a peer or being taught by a peer and 50% said the expert
      teams were an excellent method to learn the topographic anatomy. Almost all
      students applied Zoomify and CyberPrep and 75% of them found the digital
      microscopy and dissection to be a helpful or very helpful learning tool. In face
      of reduced contact hours, these forms of education compensated in part the lost
      teaching time. We observed improvement of rhetoric and presentation skills and
      self-confidence. The approaches should therefore find their constant place in the
      veterinary medicine curricula.

PMID- 19769571
TI  - Is tryptophan 'more' essential than other essential aminoacids in development? A
      morphologic study.
AB  - An ontogenetic study was designed on developing rats in uterus of mothers
      tryptophan deprived at day 1 (exp. 1) and day 14.5 (exp. 2) of conception to
      verify the supposed determining role of the serotoninergic system (SS) in sexual
      differentiation in mammals. Tryptophan-free feeding was pursued uninterruptedly
      in the litter after birth, during lactation and post-natal development.
      Tryptophan-free pregnant rats were obtained by exclusion of tryptophan sources
      from chow. In both exp. 1 and exp. 2, the litter showed at birth a significant
      physical under evolution that worsened, during post-natal development, to a much
      more marked dwarfism in exp. 1 pups. Growth hormone concentrations in both sexes
      of dwarf rats were lower than that in the control rats. At 30 days post-natal
      age, whereas exp. 1 female rats showed a right-timed onset of puberty, no
      descensus of testes could be observed in male rats of same experiment. Dwarf male
      rats showed an evident hypotrophy of the whole reproductive apparatus. In
      histological examination of testes, neither spermatogenesis nor Leydig cells have
      been observed. Moreover, dwarf female rats showed a pronounced hypotrophy of
      reproductive organs, but a normal puberal status pattern was evident. In exp. 2,
      litters showed a less pronounced dwarfism, but a normal right-timed onset of
      puberty in both male and female rats. Data indicate that role of tryptophan in
      physical and sexual maturation in both male and female rats is essential.

PMID- 19769572
TI  - Effect of maternal lead exposure on craniofacial ossification in rat fetuses and
      the role of antioxidant therapy.
AB  - Lead exposure during intrauterine life was found to result in reduced birth
      weight, impaired skeletal development and post-natal neurotoxic effects. In this
      study, the effect of pre-natal exposure to different doses of lead on the
      development of craniofacial skeleton in rat fetuses was investigated. Vitamin E
      was tested as a concomitant treatment, aiming to improve the fetotoxic effects of
      lead. Positively pregnant female rats were randomly divided into four groups;
      groups I and II (L250 and L500), exposed to lead acetate in doses of 250 and 500
      mg/l respectively, group III (L500 + E), exposed to lead acetate (500 mg/l) wit
      concomitant vitamin E and group IV (Control) which was given sodium acetate only.
      All the treatments started from the first day of gestation till the 20th day,
      where all rats were sacrificed and the fetuses were recovered. Fetuses were
      processed to alizarin red staining for ossified components. Twenty-seven bones of
      the craniofacial skeleton were studied in each fetus where the ossification was
      scored as being complete, delayed or absent. In all studied fetuses from all
      groups, changes were found only in eight bones while the remaining craniofacial
      bones were normally ossified. In affected bones there was a significant decrease
      in the number of completely ossified bones; associated with a significant
      increase of both partially ossified and absent bones in L(250) and L(500) treated
      groups when compared to the control group. These differences were more
      significant in the L(500) treated group. Giving vitamin E improved the percentage
      of completely ossified craniofacial bones and decreased the percentage of both
      partially ossified and absent bones. The most affected bone was presphenoid, then
      to a lesser extent supraoccipital, squamosal, parietal, interparietal and frontal
      bone respectively. In conclusion, lead exposure to rats during pregnancy led to
      varying degrees of fetal growth retardation as well as delayed ossification of
      some craniofacial bones which were dose dependent and the concomitant
      supplementation with vitamin E greatly improved the deleterious effect of lead.

PMID- 19769573
TI  - New frontier in digestive medicine. Abstracts of Asia Pacific Digestive Week.
      September 27-30, 2009. Taipei, Taiwan.

PMID- 19769574
TI  - Mutation in the catalytic subunit of DNA polymerase alpha influences
      transcriptional gene silencing and homologous recombination in Arabidopsis.
AB  - REPRESSOR OF SILENCING 1 (ROS1) encodes a DNA demethylase that actively removes
      DNA methylation. Mutation in ROS1 leads to transcriptional gene silencing of a T
      DNA locus that contains two genes, RD29A-LUC and 35S-NPTII, originally expressed
      in the C24 wild type. These units have different silencing regulation mechanisms:
      the former mechanism is dependent on small interfering RNA (siRNA)-directed DNA
      methylation, but the latter is not. We studied the latter gene silencing
      mechanism by screening the suppressors of the ros1 mutant using the silenced 35S
      NPTII as a selection marker gene. The polalpha/incurvata2 (icu2) gene was
      isolated as one ros1 suppressor because its mutation leads to the reactivation of
      the silenced 35S-NPTII gene. POLalpha/ICU2 encodes a catalytic subunit of DNA
      polymerase alpha. Mutation of POLalpha/ICU2 did not affect DNA methylation, but
      reduced histone H3 Lys9 dimethylation (H3K9me2) modification in the 35S promoter.
      The polalpha mutation also influences the development of the shoot apical
      meristem, and delays the G2/M phase with high expression of a G2/M marker gene
      CycB1;1:GUS. Furthermore, the frequency of homologous recombination is greater in
      the polalpha/icu2 mutant than in the C24 wild type. Our results suggest that DNA
      polymerase alpha is involved in mediating epigenetic states and in DNA homologous
      recombination in Arabidopsis.

PMID- 19769575
TI  - Closely related receptor complexes differ in their ABA selectivity and
      sensitivity.
AB  - The recent discovery of a variety of receptors has led to new models for hormone
      perception in plants. In the case of the hormone abscisic acid (ABA), which
      regulates plant responses to abiotic stress, perception seems to occur both at
      the plasma membrane and in the cytosol. The cytosolic receptors for ABA have
      recently been identified as complexes between protein phosphatases 2C (PP2C) and
      regulatory components (RCAR/PYR/PYL) that bind ABA. Binding of ABA to the
      receptor complexes inactivates the PP2Cs, thereby activating the large variety of
      physiological processes regulated by ABA. The Arabidopsis genome encodes 13
      homologues of RCAR1 and approximately 80 PP2Cs, of which six in clade A have been
      identified as negative regulators of ABA responses. In this study we characterize
      a novel member of the RCAR family, RCAR3. RCAR3 was identified in a screen for
      interactors of the PP2Cs ABI1 and ABI2, which are key regulators of ABA
      responses. RCAR3 was shown to repress ABI1 and ABI2 in vitro, and to stimulate
      ABA signalling in protoplast cells. RCAR3 conferred greater ABA sensitivity to
      the PP2C regulation than RCAR1, whereas stereo-selectivity for (S)-ABA was less
      stringent with RCAR3 as compared with RCAR1. In addition, regulation of the
      protein phosphatase activity by RCAR1 and RCAR3 was more sensitive to ABA for
      ABI1 than for ABI2. Based on the differences we have observed in transcriptional
      regulation and biochemical properties, we propose a model whereby differential
      expression of the co-receptors and combinatorial assembly of the receptor
      complexes act in concert to modulate and fine-tune ABA responses.

PMID- 19769576
TI  - Two different CC-NBS-LRR genes are required for Lr10-mediated leaf rust
      resistance in tetraploid and hexaploid wheat.
AB  - Comparative study of disease resistance genes in crop plants and their relatives
      provides insight on resistance gene function, evolution and diversity. Here, we
      studied the allelic diversity of the Lr10 leaf rust resistance gene, a CC-NBS-LRR
      coding gene originally isolated from hexaploid wheat, in 20 diploid and
      tetraploid wheat lines. Besides a gene in the tetraploid wheat variety 'Altar'
      that is identical to the hexaploid wheat Lr10, two additional, functional
      resistance alleles showing sequence diversity were identified by virus-induced
      gene silencing in tetraploid wheat lines. In contrast to most described NBS-LRR
      proteins, the N-terminal CC domain of LR10 was found to be under strong
      diversifying selection. A second NBS-LRR gene at the Lr10 locus, RGA2, was shown
      through silencing to be essential for Lr10 function. Interestingly, RGA2 showed
      much less sequence diversity than Lr10. These data demonstrate allelic diversity
      of functional genes at the Lr10 locus in tetraploid wheat, and these new genes
      can now be analyzed for agronomic relevance. Lr10-based resistance is highly
      unusual both in its dependence on two, only distantly, related CC-NBS-LRR
      proteins, as well as in the pattern of diversifying selection in the N-terminal
      domain. This indicates a new and complex molecular mechanism of pathogen
      detection and signal transduction.

PMID- 19769577
TI  - Pp IX silica nanoparticles demonstrate differential interactions with in vitro
      tumor cell lines and in vivo mouse models of human cancers.
AB  - Protoporphyrin IX (Pp IX) silica nanoparticles, developed for effective use in
      photodynamic therapy (PDT), were explored in in vitro and in vivo models with the
      ambition to improve knowledge on the role of biological factors in the
      photodamage. Pp IX silica nanoparticles are found efficient at temperature with
      extreme metabolic downregulation, which suggest a high proportion of passive
      internalization. For the first time, clearance of silica nanoparticles on tumor
      cells is established. Cell viability assessment in six tumor cell lines is
      reported. In all tumor types, Pp IX silica nanoparticles are more efficient than
      free Pp IX. A strong fluorescence signal of reactive oxygen species generation
      colocalized with Pp IX silica nanoparticles, correlates with 100% of cell death.
      In vivo studies performed in HCT 116, A549 and glioblastoma multiforme tumors
      bearing mice show tumor uptake of Pp IX silica nanoparticles with better tumor
      accumulation than the control alone, highlighting a high selectivity for tumor
      tissues. As observed in in vitro tests, tumor cell type is likely a major
      determinant but tumor microenvironment could more influence this differential
      time accumulation dynamic. The present results strongly suggest that Pp IX silica
      nanoparticles may be involved in new alternative local applications of PDT.

PMID- 19769578
TI  - Variations in photosystem I properties in the primordial cyanobacterium
      Gloeobacter violaceus PCC 7421.
AB  - We compared the optical properties of the trimeric photosystem (PS) I complexes
      of the primordial cyanobacterium Gloeobacter violaceus PCC 7421 with those of
      Synechocystis sp. PCC 6803. Gloeobacter violaceus PS I showed (1) a shorter
      difference maximum of P700 by approximately 2 nm, (2) a smaller antenna size by
      approximately 10 chlorophyll (Chl) a molecules and (3) an absence of Red Chls.
      The energy transfer kinetics in the antennae at physiological temperatures were
      very similar between the two species due to the thermal equilibrium within the
      antenna; however, they differed at 77 K where energy transfer to Red Chls was
      clearly observed in Synechocystis sp. PCC 6803. Taken together with the lower
      P700 redox potential in G. violaceus by approximately 60 mV, we discuss
      differences in the optical properties of the PS I complexes with respect to the
      amino acid sequences of core proteins and further to evolution of cyanobacteria.

PMID- 19769579
TI  - Epidermal platelet-activating factor receptor activation and ultraviolet B
      radiation result in synergistic tumor necrosis factor-alpha production.
AB  - Ultraviolet B radiation (UVB) is a potent stimulator of epidermal cytokine
      production which has been implicated in photoaggravated dermatoses. In addition
      to cytokines such as tumor necrosis factor-alpha (TNF-alpha), UVB generates
      bioactive lipids including platelet-activating factor (PAF). Our previous studies
      have demonstrated that UVB-mediated production of keratinocyte TNF-alpha is in
      part due to PAF. The current studies use a human PAF-receptor (PAF-R) negative
      epithelial cell line transduced with PAF-Rs and PAF-R-deficient mice to
      demonstrate that activation of the epidermal PAF-R along with UVB irradiation
      results in a synergistic production of TNF-alpha. It should be noted that PAF-R
      effects are mimicked by the protein kinase C (PKC) agonist phorbol myristic
      acetate, and are inhibited by pharmacological antagonists of the PKC gamma
      isoenzyme. These studies suggest that concomitant PAF-R activation and UVB
      irradiation results in a synergistic production of the cytokine TNF-alpha which
      is mediated in part via PKC. These studies provide a novel potential mechanism
      for photosensitivity responses.

PMID- 19769580
TI  - Are the fluorescent properties of the cyan fluorescent protein sensitive to
      conditions of oxidative stress?
AB  - The modifications induced by reactive oxygen species (ROS) on fluorescent
      proteins (FPs) may have important implications for live cell fluorescence
      imaging. Using quantitative gamma-radiolysis, we have studied the ROS-induced
      biochemical and photophysical perturbations on recombinant cyan fluorescent
      protein (CFP). After oxidation by the OH radical, the protein displays a modified
      RP-HPLC elution profile, while the CFP fluorescence undergoes pronounced
      decreases in intensity and lifetime, without changes in its excitation and
      emission spectra. Meanwhile, the Forster resonant energy transfer (FRET) between
      the single W(57) and the chromophore remains unperturbed. These results rule out
      a direct oxidation of the CFP chromophore and of W(57) as well as major changes
      in the protein 3D structure, but show that new fluorescent forms associated to a
      higher level of dynamic quenching have been generated. Thus, strict in situ
      controls are required when CFP is to be used for FRET studies in situations of
      oxidative activity, or under strong illumination.

PMID- 19769581
TI  - Photosensitized oxidation of tetrabromobisphenol a by humic acid in aqueous
      solution.
AB  - The brominated flame retardant 3,3',5,5'-tetrabromobisphenol A (TBBPA) may
      accumulate in the environment, including surface waters, and degrade there to
      potentially toxic products. We have previously shown that singlet oxygen (1O2),
      produced by irradiation of rose bengal with visible light, oxidizes Triton X-100
      solubilized TBBPA to yield the 2,6-dibromo-p-benzosemiquinone anion radical while
      consuming oxygen (Environ. Sci. Technol.42, 166, 2008). Here, we report that a
      similar 1O2-induced oxidation can be initiated in aqueous solutions by the
      irradiation of TBBPA dissolved in a humic acid (HA) solution. HA is a known weak
      1O2 photosensitizer and we indeed detected the infrared 1O2 phosphorescence from
      HA preparations in D2O. When an aqueous preparation of HA was irradiated (lambda
      > 400 nm) in the presence of TBBPA, oxygen was consumed, and the 2,6-dibromo-p
      benzosemiquinone anion radical was generated and detected using electron
      paramagnetic resonance. Radical formation and oxygen consumption were inhibited
      by sodium azide, a singlet oxygen quencher. Our results suggest that solar
      radiation, in the presence of HA, may play an important role in the
      photodegradation of TBBPA in the aquatic environment.

PMID- 19769582
TI  - Remote monitoring of cardiovascular implantable electronic devices: new questions
      raised.

PMID- 19769583
TI  - Initial experience of pacing with a lumenless lead system in patients with
      congenital heart disease.
AB  - BACKGROUND: Long-term pacing is frequently necessary in patients with congenital
      heart disease (CHD). Preservation of ventricular function and avoidance of venous
      occlusion is important in these patients. Site-selective pacing with a smaller
      diameter lead is achievable with the model 3830 lead (SelectSecure, Medtronic
      Inc., Minneapolis, MN, USA), which was specifically designed to target these
      complications. We describe our initial experience with the Model 3830 lead in
      patients with CHD. METHODS: Retrospective analysis of all patients undergoing
      site-selective implantation of a Model 3830 lead(s) from two congenital heart
      centers (Bristol, UK, and Dublin, Ireland) from October 2004 until February 2008.
      RESULTS: We implanted 139 SelectSecure leads (atrial n=70; ventricular n=69) in
      90 patients (57 male) with CHD. Median age at implantation: 13.4 years (1.1-59.2
      years), median weight: 43 kg. Sixty-nine patients (76%) were children (<18
      years). Indications for lead implantation included atrioventricular block (n=55),
      sinus node disease (n=18), implantable cardiac defibrillator (n=12),
      antitachycardia pacing (n=4), and cardiac resynchronization (n=1). Twenty-two
      patients underwent pre-existing lead extraction during the same procedure. All
      the attempted procedures resulted in successful pacing. One patient had a
      significantly raised threshold at implantation. There was no procedural
      mortality. There were two procedural complications. Three patients required lead
      repositioning for increasing thresholds early postprocedure (<6 weeks). Four
      leads (2.9%) had displaced on median follow-up of 21.8 months (0.5-42 months).
      CONCLUSIONS: The Model 3830 lead is safe and effective in patients with CHD. This
      is a technically challenging patient group yet procedural complication and lead
      displacement rates are acceptable.

PMID- 19769584
TI  - Prediction of anxiety symptoms in preschool-aged children: examination of
      maternal and paternal perspectives.
AB  - BACKGROUND: Little is known about risk factors for anxiety in young children. The
      current study investigated the value of a set of theoretically derived risk
      factors to predict symptoms of anxiety in a sample of preschool-aged children.
      METHODS: Mothers (n = 632) and fathers (n = 249) completed questionnaires twice,
      12 months apart. Measures were selected to assess several risk factors derived
      from current theory, including parental negative affectivity, child inhibition,
      parent overprotection, and impact of life events. RESULTS: Even at this young age
      anxiety across 12 months was moderately to highly stable (r's = .75 and .74 based
      on maternal and paternal report respectively). Over and above this stability,
      according to maternal report, anxiety at 12 months was significantly predicted by
      prior maternal overprotection, impact of negative life events, child's
      inhibition, and maternal negative affectivity. According to paternal report,
      anxiety at 12 months was significantly predicted by prior paternal overprotection
      and impact of negative life events. The models did not differ significantly for
      girls and boys. CONCLUSIONS: The results support theories of the development of
      anxiety, especially the role of parental and external environmental factors, and
      point to possible targets for prevention of heightened anxiety in young children.

PMID- 19769585
TI  - Genetic and attachment influences on adolescents' regulation of autonomy and
      aggressiveness.
AB  - BACKGROUND: Adolescence is a time when intense emotions are elicited within the
      parent-adolescent relationship, often when autonomy subjectively is endangered.
      As emotion dysregulation is one of the risk processes for the development of
      psychopathology, adolescence may be perceived as a highly sensitive period for
      maladjustment. Inter-individual differences in emotionality and emotion
      regulation have been shown to be influenced or moderated by molecular genetic
      differences in the serotonin transporter gene (5-HTT) and by attachment patterns.
      We investigated whether both the 5-HTT and attachment are associated with
      emotionality and emotion regulation in an observed adolescent-mother interaction
      and the personality traits aggressiveness and anxiety in adolescence. METHODS:
      Ninety-one adolescents at age 12 were observed in interaction with their mothers
      during a standardized emotion-eliciting social task to assess emotionality and
      emotion regulation in relation to autonomy. Adolescents' aggressiveness and
      anxiety were assessed by mother report. Concurrent attachment quality was
      determined by an attachment interview. DNA samples were collected in order to
      assess the 5-HTTLPR, a repeat polymorphism in the promoter region of the
      serotonin transporter gene. RESULTS: While the short allele of the serotonin
      transporter gene was associated with a higher overall rate of autonomy behaviors,
      attachment security was related to more agreeable and less hostile autonomy. A
      significant interaction revealed a moderating effect of attachment security.
      Carriers of the short version of the 5-HTTLPR showed more agreeable autonomy when
      they had a secure attachment behavior strategy but showed more hostile autonomy
      when they were insecurely attached. Carriers of the short version of the 5-HTTLPR
      and insecurely attached adolescents were rated as more aggressive. CONCLUSIONS:
      The study suggests a gene-attachment interaction in adolescents where the
      adolescent's attachment status moderates a genetically based higher negative
      reactivity in response to threats to autonomy in social interactions.

PMID- 19769586
TI  - The influence of sex on the course and psychiatric correlates of ADHD from
      childhood to adolescence: a longitudinal study.
AB  - BACKGROUND: Little is known about the influence of sex on the course of attention
      deficit/hyperactivity disorder (ADHD) and its comorbid psychiatric conditions.
      The purpose of this study was to examine the effect of sex on the course and
      psychiatric correlates of ADHD from childhood into adolescence. METHODS: Two
      identically designed, longitudinal, case-control family studies of male and
      female probands with and without ADHD and their siblings were combined. All
      subjects were blindly assessed with structured diagnostic interviews. Among
      subjects with a lifetime history of ADHD (n = 471, mean age 11.5 +/- 4.3 years at
      baseline), we used linear growth curve models to estimate the effect of time on
      the change in ADHD symptoms, and whether this effect differed by sex. We also we
      examined the effect of sex on the association between ADHD and the longitudinal
      progression of comorbid psychopathology using structural equation models.
      RESULTS: We found no evidence that sex moderated the effect of age on ADHD
      symptoms; in both genders, age exhibited a similar effect on the decline of ADHD
      symptoms. However, the female sample demonstrated greater stability in comorbid
      psychopathology from childhood into adolescence. Furthermore, we found that the
      stability of comorbid psychopathology in females remained significant after
      accounting for the correlation between adolescent psychopathology and adolescent
      ADHD. In males, childhood and adolescent comorbid psychopathology were no longer
      correlated when adolescent ADHD was taken into account. CONCLUSIONS: Our findings
      indicate that while the course of ADHD across childhood and adolescence did not
      differ between males and females, patterns of psychiatric comorbidity were
      conditional on sex. Future studies should explicitly test how sex modifies the
      associations between ADHD and risk factors and ADHD and associated functional
      outcomes.

PMID- 19769587
TI  - Pseudomonas fluorescens CHA0 can kill subterranean termite Odontotermes obesus by
      inhibiting cytochrome c oxidase of the termite respiratory chain.
AB  - Pseudomonas fluorescens CHA0 has been shown to suppress the growth of a wide
      range of microbial plant pathogens as well as invertebrate pests such as root
      nematodes. Hydrogen cyanide, a secondary metabolite produced by the bacterium,
      has been credited as being one of the determinants of its biocontrol ability. The
      use of biocontrol agents against social insect pests such as termite Odontotermes
      obesus has limitations because of behavioural adaptations that include (1)
      removal of the pathogen when grooming by the termites and (2) isolation of
      infested members of the colony. In this study, we show that cyanide of bacterial
      origin may inhibit cytochrome c oxidase (CCO) of the termite respiratory chain
      and demonstrate that HCN-producing bacteria such as P. fluorescens can actually
      kill a macroscopic insect pest by cyanide poisoning. This ability of pseudomonad
      metabolites such as cyanide, which can bring about pest death by blocking
      respiration through inhibition of CCO rather than infection or predation, can
      potentially overcome the behavioural adaptations of social insect pests such as
      termites and represents an attractive option for insect pest management.

PMID- 19769588
TI  - Depolarization amplitude and Ca2+ -inflow control the time course of quantal
      releases at murine motor nerve terminals.
AB  - In order to test whether the time courses of quantal releases after a
      depolarization pulse are affected by the depolarization amplitude, time courses
      were measured for small depolarization pulses that elicited close to threshold
      releases and for large depolarizations that elicited releases approaching
      saturation level. Diaphragms of young mice were excised and superfused with
      Bretag's solution at 18 degrees C. Synaptic currents were elicited and recorded
      through a perfused macropatch pipette. Releases elicited by threshold
      depolarizations rose earlier than releases elicited by saturation
      depolarizations. The short delays in the rising phases of release after large
      depolarizations may be due to the shift of Ca(2+) currents flowing during the
      pulse to tail currents. After its peak, release decayed with a time constant tau.
      For saturation depolarizations tau was about 0.3 ms, and for threshold
      depolarizations tau increased up to 0.8 ms. In order to differentiate between the
      effects of variations in Ca(2+) inflow and in depolarization, the amplitudes of
      large depolarization pulses were held constant while the amount of release was
      depressed by halving the Ca(2+) concentration at the terminal. The time course of
      the lowered releases was slightly delayed while tau remained at 0.3 ms as typical
      for saturation depolarizations. Double pulse facilitation unexpectedly revealed a
      short phase of depression of release after the pulse. This depression may
      contribute to the rapid decay (tau) of release after large depolarizations. The
      dependence of tau on depolarization amplitude indicates that the final phase of
      the time course of release is largely controlled by the amplitude of the
      preceding depolarization.

PMID- 19769589
TI  - Oxytocin injected into the ventral subiculum or the posteromedial cortical
      nucleus of the amygdala induces penile erection and increases extracellular
      dopamine levels in the nucleus accumbens of male rats.
AB  - Oxytocin (20-100 ng) was found to be able to induce penile erection when injected
      unilaterally into the ventral subiculum or the posteromedial cortical nucleus of
      the amygdala of male rats. The pro-erectile effect started mostly 30 min after
      treatment and was abolished by the prior injection of d(CH(2))(5)Tyr(Me)(2)
      Orn(8)-vasotocin (1-2 microg), an oxytocin receptor antagonist, into the ventral
      subiculum or posteromedial cortical nucleus. Oxytocin-induced penile erection
      occurred 15 min after the increase in the concentration of extracellular dopamine
      and its metabolite 3,4-dihydroxyphenylacetic acid in the dialysate obtained from
      the nucleus accumbens, which was also abolished by d(CH(2))(5)Tyr(Me)(2)-Orn(8)
      vasotocin. The pro-erectile effect of oxytocin was also reduced by cis
      flupentixol (2 and 5 microg), a dopamine receptor antagonist, injected into the
      nucleus accumbens, and by (+)MK-801 (5 microg), a noncompetitive N-methyl-d
      aspartate receptor antagonist, injected into the ventral tegmental area, but not
      into the nucleus accumbens. Together with studies showing that glutamatergic
      efferents from the ventral subiculum/posteromedial cortical nucleus of the
      amygdala to other areas of the limbic system modulate the activity of mesolimbic
      dopaminergic neurons, these findings suggest that oxytocin injected into these
      areas increases glutamatergic neurotransmission in the ventral tegmental area.
      This, in turn, activates mesolimbic dopaminergic neurons, leading to penile
      erection. These results provide evidence that the ventral subiculum and the
      posteromedial cortical nucleus of the amygdala participate in a neural circuit
      that controls not only the consummatory aspects of sexual behaviour (e.g. penile
      erection and copulatory performance), but also its motivational/reward aspects,
      confirming a key role of oxytocin and dopamine in these processes.

PMID- 19769590
TI  - Cocaine-induced stereotypy is linked to an imbalance between the medial
      prefrontal and sensorimotor circuits of the basal ganglia.
AB  - The dysfunction of basal ganglia circuits related to stereotyped motor activity
      was analysed using the well-established model of cocaine-induced stereotypy in
      the rat. We examined and compared the neurochemical and electrophysiological
      effects occurring in medial prefrontal and sensorimotor basal ganglia circuits of
      the dorsal striatum after cocaine injection in sensitized and non-sensitized
      rats. Acute injections of cocaine (25 mg/kg), not inducing stereotyped behaviour,
      affected both medial prefrontal and sensorimotor circuits in a similar way: (i) a
      mild and delayed increase and decrease of N-methyl-D-aspartate-evoked dopamine
      and acetylcholine release, respectively and (ii) a marked decrease of cortically
      evoked inhibition of substantia nigra pars reticulata neurons revealing an
      imbalance of information transmission between the direct and indirect trans
      striatal pathways. In contrast, following sensitization to cocaine, a challenge
      injection of the same dose of cocaine, generating strong stereotyped behaviour,
      provoked neurochemical and electrophysiological effects only in the medial
      prefrontal but not in the sensorimotor circuits: (i) a strong increase of
      dopamine and decrease of acetylcholine release in the medial prefrontal territory
      of the dorsal striatum and (ii) a reduction of all inhibitory and excitatory
      components of the responses evoked in substantia nigra pars reticulata by medial
      prefrontal stimulation. Therefore, these data disclose distinct reactivity of the
      medial prefrontal and sensorimotor circuits of the basal ganglia to repeated
      cocaine administration leading to stereotyped behaviour induced by subsequent
      cocaine challenge. Thus, we suggest that stereotyped behaviour is correlated to
      an imbalance between the medial prefrontal and sensorimotor circuits of the basal
      ganglia resulting in a loss of control of motor behaviour.

PMID- 19769591
TI  - Involvement of the lateral orbitofrontal cortex in drug context-induced
      reinstatement of cocaine-seeking behavior in rats.
AB  - Orbitofrontal cortex (OFC) damage produces impaired decision-making, impulsivity
      and perseveration and potentially contributes to compulsive drug seeking in
      cocaine users. To further explore this phenomenon, we assessed the role of the
      lateral OFC (lOFC) in drug context-induced cocaine-seeking behavior in the
      reinstatement model of drug relapse. Rats were trained to lever press for
      intravenous cocaine infusions in a distinct environmental context (cocaine-paired
      context) followed by extinction training in a different context (extinction
      paired context). Reinstatement of cocaine seeking (non-reinforced lever presses)
      was assessed in the cocaine context in the absence of response-contingent
      stimuli. In Experiment 1, we evaluated whether acute inhibition of lOFC output
      alters context-induced cocaine-seeking behavior by infusing the GABA(B + A)
      agonists (baclofen + muscimol) or vehicle into the lOFC immediately before
      exposure to the cocaine-paired context. In Experiments 2 and 3, we assessed how
      prolonged loss of lOFC output affects drug context-induced cocaine seeking by
      administering bilateral N-methyl-d-aspartic acid or sham lesions of the lOFC
      either before or after self-administration and extinction training. Remarkably,
      IOFC functional inactivation attenuated, post-training lesions failed to alter
      and pre-training lesions potentiated drug context-induced cocaine seeking without
      altering responding in the extinction context. These results suggest that neural
      activity in the lOFC promotes context-induced cocaine-seeking behavior. However,
      prolonged loss of lOFC output enhances the motivational salience of cocaine
      paired contextual stimuli probably by eliciting compensatory neuroadaptations,
      with the effects of post-training lOFC lesions reflecting an intermediate state
      of compensatory neuroplasticity. Overall, these findings support the idea that
      OFC dysfunction may promote cue reactivity and enhance relapse propensity in
      cocaine users.

PMID- 19769592
TI  - Distortion of auditory space in hemianopia.
AB  - Sound localization was investigated in patients with homonymous hemianopia, a
      visual field defect characterized by a loss of vision in one hemifield that is
      caused by unilateral brain lesions involving the visual cortex or its afferents.
      The primary aim was to clarify whether or not the known distortion of visual
      space in hemianopia results in processes of long-term cross-modal spatial
      adaptation, thus eventually inducing related alterations in auditory space
      perception. For this purpose, patients were tested by using tasks of either head
      pointing or manual pointing to acoustic targets in the azimuthal plane, under
      anechoic conditions in total darkness. The results obtained with both tasks
      consistently indicated slight, but significant, systematic errors compared with
      normal controls. In particular, the errors found can be interpreted by both
      rotation and compression of auditory space toward the anopic side. These findings
      can be explained by a visual miscalibration of the auditory space, as has been
      analogously demonstrated in studies on normal-sighted subjects after exposure to
      consistent auditory-visual disparity, for example by wearing prism lenses. The
      precision in sound localization of hemianopic patients was generally reduced
      across both hemispaces. Taken together, one may conclude that processes of cross
      modal spatial adaptation, but not those of compensatory plasticity, occurred in
      patients with hemianopia.

PMID- 19769593
TI  - Remote facilitation of supraspinal motor excitability depends on the level of
      effort.
AB  - Stretch reflexes and motor-evoked potentials (MEPs) of a muscle are facilitated
      when performing intensive contraction of muscles located in a different segment
      (remote effect). We investigated to what extent the remote effect on MEPs in the
      flexor carpi radialis (FCR) in humans is modulated during sustained maximal and
      submaximal voluntary contractions of the ipsilateral quadriceps (remote muscle).
      We found that even when the force of maximal voluntary contraction (MVC) of the
      remote muscle declined during sustained MVC, the magnitude of the remote effect
      on MEPs remained constant. Maximal electrical stimulation of the remote muscle
      and transcranial magnetic stimulation of the corresponding motor cortex revealed
      that the level of voluntary activation gradually decreased during the sustained
      MVC. The motor response in the FCR following magnetic stimulation at the level of
      the foramen magnum, which preferentially elicits muscle response as a direct
      response of the corticospinal tract, was not modified by the remote effect during
      the sustained MVC. This finding suggested that the excitability of the spinal
      motoneuron pool remained constant. In contrast to the sustained MVC, during
      sustained submaximal contraction of the remote muscle, the magnitude of the
      remote effect on MEPs gradually increased as muscle fatigue developed. These
      findings suggest that the remote effect on MEPs was dependent on the level of
      effort driving the remote muscle, but not on the actual level of force output of
      the remote muscle, and that the origin of the remote effect was supraspinal,
      putatively upstream of the primary motor cortex.

PMID- 19769595
TI  - Leukemia - methods and protocols.

PMID- 19769594
TI  - Olfactory-learning abilities are correlated with the rate by which intrinsic
      neuronal excitability is modulated in the piriform cortex.
AB  - Long-lasting modulation of intrinsic neuronal excitability in cortical neurons
      underlies distinct stages of skill learning. However, whether individual
      differences in learning capabilities are dependent on the rate by which such
      learning-induced modifications occur has yet to be explored. Here we show that
      training rats in a simple olfactory-discrimination task results in the same
      enhanced excitability in piriform cortex neurons as previously shown after
      training in a much more complex olfactory-discrimination task. Based on their
      learning capabilities in the simple task, rats could be divided to two groups:
      fast performers and slow performers. The rate at which rats accomplished the
      skill to perform the simple task was correlated with the time course at which
      piriform cortex neurons increased their repetitive spike firing. Twelve hours
      after learning, neurons from fast performers had reduced spike frequency
      adaptation as compared with neurons from slow performers and controls. Three days
      after learning, spike frequency adaptation was reduced in neurons from SP, while
      neurons from fast performers increased their spike firing adaptation to the level
      of controls. Accordingly, the post-burst AHP was reduced in neurons from fast
      performers 12 h after learning and in neurons from slow performers 3 days after
      learning. Moreover, the differences in learning capabilities between fast
      performers and slow performers were maintained when examined in a different,
      complex olfactory-discrimination task. We suggest that the rate at which neuronal
      excitability is modified during learning may affect the behavioral flexibility of
      the animal.

PMID- 19769596
TI  - Report of two double-blind randomized placebo-controlled pilot studies of a
      carbohydrate-rich nutrient mixture for treatment of seasonal affective disorder
      (SAD).
AB  - We investigated a carbohydrate-rich nutrient-drink mix for treatment of seasonal
      affective disorder (SAD). This mixture may contribute to brain serotonin
      synthesis, potentially exerting an antidepressant effect and controlling
      carbohydrate cravings. Two successive double-blind placebo-controlled studies
      were performed. In Study 1, 18 subjects (50% women; mean age 43 +/- 15 years)
      with SCID-diagnosed SAD were randomized to 12 days of twice daily carbohydrate
      beverage (CHO) containing mixed starches, or a placebo beverage (PRO) containing
      the CHO mix plus casein protein to dampen serotonin synthesis. Following a 2-day
      washout, subjects were crossed over to the other treatment for 12 days. In Study
      2, 32 subjects (63% women; mean age 46 +/- 14 years) with SCID-diagnosed SAD were
      randomized to 21 days of CHO or PRO. Efficacy in both studies was determined by
      the first 17 items of the Hamilton Depression Rating Scale (HAM-D-28), an
      appetite questionnaire, and regular weighing. In Study 1, response rates were 50%
      for both groups. Remission rates favored CHO (50% vs. 38%), as did the decrease
      in the HAM-D-17 score, but differences were nonsignificant. In Study 2, response
      rates were 71% for CHO and 76% for PRO, and remission rates were 71% for each
      group. Both treatment groups experienced significant improvement in HAM-D-17
      scores within 1 week of treatment, which continued through the entire study
      period. Weight change did not differ significantly between treatment groups in
      either study. The drink mix was well tolerated and treatment adherence was high.
      Both the active and placebo intervention were effective in alleviating symptoms
      of SAD. Replication studies in larger samples appear warranted.

PMID- 19769597
TI  - Neurological and cardiovascular adverse events associated with antimanic
      treatment in children and adolescents.
AB  - To identify the factors associated with incident neurological and cardiovascular
      adverse events in children and adolescents treated with antimanic agents, a
      retrospective, longitudinal study was conducted. Medicaid medical and pharmacy
      claims between January 1996 and December 2005 were used to identify 3657 children
      and adolescents prescribed antimanic medications, and a random sample of 4500
      children not treated with psychotropic medications. All adverse events examined
      (sedation/drowsiness, headaches, involuntary movements/extrapyramidal symptoms
      (EPS), cardiovascular events, hypertension, and orthostatic hypotension) were
      more prevalent in the antimanic-treated cohort. The odds of developing incident
      sedation/drowsiness and headaches were significantly higher for those prescribed
      carbamazepine, and co-prescribed selective serotonin reuptake inhibitors or
      antipsychotics. The odds of incident involuntary movements/EPS were significantly
      higher for those co-prescribed antimanic and antipsychotic agents, and those with
      comorbid central nervous system (CNS), organic brain disorders/mental
      retardation, or epilepsy. Incident cardiovascular events, hypertension, and
      orthostatic hypotension odds were significantly higher for those co-prescribed
      antimanic agents and antipsychotics, or those with comorbid epilepsy or metabolic
      conditions. Co-prescription of antimanic and antipsychotic agents is more likely
      associated with neurological and cardiovascular adverse reactions, especially in
      young patients with preexisting CNS/neurological disorders.

PMID- 19769598
TI  - Neuroendocrine-related adverse events associated with antidepressant treatment in
      children and adolescents.
AB  - There is only limited community-based practice safety information available
      regarding antidepressant use in pediatric patients. This study identifies the
      factors associated with incident neuroendocrine-related metabolic, digestive, and
      sexual/reproductive adverse events in children and adolescents treated with
      antidepressants. A retrospective cohort design evaluating Medicaid medical and
      pharmacy claims between January, 1996 and December, 2005 was employed for 11970
      children and adolescents prescribed an antidepressant medication, and a random
      sample of 4500 children not treated with psychotropic medications. Incident
      obesity/weight gain, Type 2 diabetes mellitus, and dyslipidemia were more likely
      for those prescribed selective serotonin reuptake inhibitors (SSRIs) (OR = 1.49;
      1.37; 1.44), whereas Type 2 diabetes mellitus and dyslipidemia were more likely
      for those prescribed weight-inducing antidepressants (ORs = 1.26; 1.24), and
      those with pre-existing endocrinopathies (ORs = 3.96; 1.90), controlling for the
      effects of co-prescribed mood stabilizers or antipsychotics. Incident
      nausea/vomiting was less likely for those taking SSRIs (OR = 0.78). Females and
      children under 12 years of age were more likely to develop these adverse effects.
      Practitioners need to carefully consider the neuroendocrine- related adverse
      effects of SSRI antidepressant agents in particular, especially in individuals
      with comorbid endocrine conditions, and those co-prescribed other classes of
      psychotropic medications.

PMID- 19769599
TI  - RESEARCH: Validation of the Massachusetts General Hospital Antidepressant
      Treatment History Questionnaire (ATRQ).
AB  - The low rate of response to antidepressants in treatment resistant depression
      (TRD) justifies studies of next-step therapies following a treatment failure. In
      TRD clinical trials, it is important to verify the accurate diagnosis of
      treatment resistance for all enrolled subjects using a reliable and valid
      instrument. Self-rated scales can reduce the impact of investigator bias and
      reduce the time burden for clinical researchers. The Massachusetts General
      Hospital (MGH) Antidepressant Treatment Response Questionnaire (ATRQ) is a self
      rated scale used to determine treatment resistance in major depressive disorder
      (MDD). The ADAPT-A study is a multi-center double-blind, placebo-controlled study
      of low-dose aripiprazole adjunctive to ADT among outpatients with TRD. At the
      screening assessment, potential subjects completed the MGH ATRQ. The ADAPT-A
      medical monitors subsequently performed remote patient interviews and obtained
      detailed medication histories. The data obtained from the MGH ATRQ and by the
      medical monitors were compared for congruency. Of the 186 patients enrolled by
      the local sites, no subjects deemed treatment resistant by the MGH ATRQ were
      found to be nonresistant by the medical monitors. In 76.3% (n = 142) of the
      subjects, the number of failed adequate antidepressant trials reported by the MGH
      ATRQ was concordant with the data collected by medical monitors. In 16.1% (n =
      30) of all cases, the medical monitors found a greater number of failed trials;
      in 7.5% (n = 14) of cases, the medical monitors found fewer failed medication
      trials. The discrepancy was by more than one medication trial in only 4.0% (n =
      7) of cases. We found the MGH ATRQ to be relatively concordant in its assessment
      of treatment resistance in depression compared with independent clinical
      researchers. Although the MGH ATRQ tended to underreport the number of
      unsuccessful treatment trials relative to the clinical interviews, its accuracy
      in cases it detected was confirmed by raters.

PMID- 19769600
TI  - Extracellular adherence protein (Eap) from Staphylococcus aureus does not
      function as a superantigen.
AB  - Extracellular adherence protein (Eap) from Staphylococcus aureus has been
      reported to have strong anti-inflammatory properties, which make Eap a potential
      anti-inflammatory agent. However, Eap has also been demonstrated to trigger T
      cell activation and to share structural homology with superantigens. In this
      study, we focused on whether Eap fulfilled the definition criteria for a
      superantigen. We demonstrate that T-cell activation by Eap is dependent on both
      major histocompatibility complex class II and intercellular adhesion molecule
      type 1, that cellular processing is required for Eap to elicit T-cell
      proliferation, and that the kinetics of proliferation resemble the profile of a
      conventional antigen and not that of a superantigen.

PMID- 19769601
TI  - Molecular epidemiology of extended-spectrum beta-lactamase-producing Klebsiella
      pneumoniae strains in a university hospital in Tunis, Tunisia, 1999-2005.
AB  - During a period of 6 years and 5 months (January 1999 to May 2005), 103 extended
      spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae isolates, each
      from an individual patient or site, were collected at Mongi Slim University
      Hospital Centre, Tunis, Tunisia. The objectives of our work were the
      characterization of the bla genes encoding ESBLs, the investigation of clonal
      diversity of strains, and identification of the transmission modes of the
      resistance genes. We carried out detection by PCR and sequencing of the bla(SHV),
      bla(CTX-M) and bla(TEM) genes, transferability studies, plasmid replicon typing,
      and analysis by multilocus sequence typing (MLST) on selected isolates. Forty
      seven isolates were found to be producers of CTX-M-type ESBLs, of which 43 were
      CTX-M-15, two CTX-M-14 and two CTX-M-27. Fifty-eight isolates were producers of
      SHV-12, and three were producers of SHV-2a. More than one ESBL was detected in
      seven isolates, as five produced both CTX-M-15 and SHV-12, and two produced both
      CTX-M-27 and SHV-12. By a PCR-based replicon typing method, the plasmids carrying
      the bla(SHV-2a) or bla(CTX-M-15) genes were assigned to IncFII or, more rarely,
      to IncL/M types. Of 12 plasmids carrying the bla(SHV-12) gene, only one could be
      typed: it was positive for the HI2 replicon. The MLST results showed large
      genetic background diversity in the SHV-12-producing isolates and dissemination
      of specific clones of the CTX-M-15-producing isolates within the same ward and
      among wards, and suggested endemicity with horizontal dissemination of the
      bla(CTX-M-15) and the bla(SHV-12) genes.

PMID- 19769602
TI  - Frontiers in research series: Stroke. Introduction.

PMID- 19769603
TI  - Secretory control: evidence for agonist regulation of post-fusion vesicle
      behaviour.
AB  - 1. Here, we review recent work on vesicular secretion, with a focus on the
      control of post-fusion events as a means of regulating secretory output. 2. In
      the classical model of secretion, each fused vesicle releases the entirety of its
      content in an all-or-none manner. In this way, the secretory output of a cell is
      controlled by regulating the numbers of fused vesicles. The realisation that post
      fusion events can control secretory output leads to a distinct model of partial
      release of vesicle content. 3. Recent work shows that post-fusion events are
      under cellular control. Further, new data from our laboratory demonstrates
      agonist-dependent regulation of fusion pore behaviour. 4. We conclude that post
      fusion events are not epiphenomena, but are likely an important mechanism of
      secretory control.

PMID- 19769604
TI  - Control of blood pressure in the absence of sympathetic nerves: is it all about
      increased variability?

PMID- 19769605
TI  - Resuscitation with Na+/H+ exchanger inhibitor in traumatic haemorrhagic shock:
      cardiopulmonary performance, oxygen transport and tissue inflammation.
AB  - 1. The aim of the present study was to examine the effects of inhibition of the
      Na(+)/H(+) exchanger (NHE-1) on cardiopulmonary performance, oxygen carrying
      capacity and tissue inflammation in a pig model of traumatic haemorrhage
      resuscitation. 2. In 12 instrumented anaesthetized pigs, traumatic haemorrhage
      was modelled by producing tibia fractures, followed by haemorrhage of 25 mL/kg
      for 20 min, and then a 4 mm hepatic arterial tear with surgical repair after 20
      min. Animals then underwent low-volume fluid resuscitation with either Hextend
      (vehicle; n = 6; Hospira, Lake Forest, IL, USA) or 3 mg/kg BIIB513 (an NHE-1
      inhibitor) + Hextend (n = 6). The experiment was terminated 6 h after the
      beginning of resuscitation. 3. Compared with vehicle-treated controls, the
      addition of NHE-1 inhibition with BIIB513 significantly improved the left
      ventricle stroke work index and attenuated increases in pulmonary arterial
      pressure and pulmonary vascular resistance. Furthermore, BIIB513 treatment
      significantly increased the oxygenated haemoglobin ratio, blood oxygen content
      and mixed venous blood oxygen saturation and improved blood oxygen delivery. In
      addition, BIIB513 treatment reduced lung tissue levels of interleukin-6 by 80%,
      tumour necrosis factor-alpha by 37% and myeloperoxidase activity by 38%. Nuclear
      factor-kappaB DNA binding activity in the lung was also slightly and
      significantly attenuated following BIIB513 treatment. 4. In conclusion, the
      present study shows that NHE-1 inhibition facilitates the response to fluid
      resuscitation after traumatic haemorrhage by improving cardiac function,
      pulmonary vascular function and oxygen carrying capacity, which results in
      reduced tissue inflammatory injury.

PMID- 19769606
TI  - Effect of antihypertensive drug therapy on short-term heart rate variability in
      newly diagnosed essential hypertension.
AB  - 1. Abnormalities of cardiac autonomic regulation are a potential mechanism for
      morbidity despite blood pressure (BP) lowering in hypertension. Analysis of short
      term (5 min) heart rate variability (HRV) provides a non-invasive probe of
      autonomic regulation of sino-atrial (SA) node automaticity. 2. We hypothesized
      that antihypertensive drug therapy would be associated with an increase in 5 min
      overall HRV, along with a decrease in blood pressure (BP), at 8 weeks follow up
      in subjects with newly diagnosed, never-treated essential hypertension. 3. One
      hundred and fifty patients (84 men and 66 women; mean (+/-SD) age 48 +/- 10
      years) with newly diagnosed essential hypertension were divided to five groups of
      30 patients each to receive one of the following antihypertensive drugs (or drug
      combinations): 5 mg/day amlodipine; 50 mg/day atenolol; 5 mg/day enalapril; 25
      mg/day hydrochlorothiazide; or a combination of 5 mg/day amlodipine and 50 mg/day
      atenolol. 4. The only significant change in HRV indices was an increase in total
      variability of RR intervals and an increase in high-frequency (HF) RR interval
      spectral power in the amlodipine + atenolol-treated group (P < 0.05). 5. The
      results indicate that there is a dissociation between changes in short-term HRV
      and mean RR interval and BP lowering in patients with newly diagnosed
      hypertension. 6. We interpret the increase in HF RR interval spectral power in
      the amlodipine + atenolol-treated group as being due to an increase in vagal
      modulation of RR intervals and/or diminution in sympathetic restraint of
      respiratory sinus arrhythmia.

PMID- 19769607
TI  - Proteinase-activated receptor-2 (PAR2) and mouse osteoblasts: regulation of cell
      function and lack of specificity of PAR2-activating peptides.
AB  - 1. Using synthetic proteinase-activated receptor-2 (PAR(2))-activating peptides
      (PAR(2)APs) corresponding to the tethered ligand domain of the extracellular N
      terminus of PAR(2) to mimic the actions of activating proteinases and using
      primary cultures of calvarial osteoblasts derived from both wild-type (WT) and
      PAR(2)-null (KO) mice, we investigated the potential role of PAR(2) in regulating
      osteoblast function. 2. Primary calvarial osteoblasts from WT and KO mice were
      evaluated for their growth kinetics and mineralization in the absence of PAR(2)
      agonists and for their responses in a variety of functional assays to the
      PAR(2)APs Ser-Leu-Ile-Gly-Arg-Leu-amide (SLIGRL-NH(2)) and 2-furoyl-Leu-Ile-Gly
      Arg-Leu-Orn-amide (2-fLIGRLO-NH(2)), as well as to trypsin. 3. In contrast with
      WT cells, PAR(2)-KO osteoblasts did not exhibit increased collagen Type I mRNA
      expression in response to SLIGRL-NH(2). When grown in serum-containing medium, KO
      cells increased in number more rapidly than WT cells, an effect that could be
      attributed to decreased apoptosis rather than increased proliferation.
      Surprisingly, in both WT and KO osteoblasts, the two PAR(2)APs induced
      mobilization of intracellular calcium stores. Similarly, the PAR(2)APs inhibited
      serum deprivation-induced apoptosis and parathyroid hormone-, 1,25
      dihydroxyvitamin D(3)- or interleukin-11-induced mineralization in WT and KO
      cells. 4. We conclude that PAR(2) plays a role in osteoblast survival and
      collagen Type I mRNA induction and that osteoblasts can respond to the PAR(2)APs
      via both PAR(2)-dependent and -independent mechanisms.

PMID- 19769608
TI  - Central and baroreflex control of heart period during the wake-sleep cycle in
      consomic rats with different genetic susceptibility to hypertension.
AB  - 1. In spontaneously hypertensive rats (SHR), the contributions of the baroreflex
      and central autonomic commands to the control of heart period (HP) vary among
      wake-sleep states and are impaired during quiet wakefulness and rapid eye
      movement sleep (REMS), respectively. 2. Dahl salt-sensitive (SS) rats are
      genetically susceptible to salt-sensitive hypertension, the development of which
      depends on diet. Substitution of chromosome 13 of SS rats with that of Brown
      Norway rats confers salt-resistance to consomic SS-13BN rats. 3. In the present
      study, we tested whether differences in the central and baroreflex contributions
      to HP control occur among wake-sleep states in SS and SS-13BN rats and reflect
      genetic susceptibility to hypertension. Rats (n = 5 per group) were fed a
      prohypertensive diet late during development to minimize hypertension in SS rats
      and were instrumented with an arterial catheter and electrodes for discriminating
      wake-sleep states. 4. The cross-correlation function between HP and blood
      pressure indicated that, in SS and SS-13BN rats, the contributions of the
      baroreflex and central commands to the control of HP differed significantly among
      wake-sleep states, with central commands outweighing the baroreflex in REMS.
      However, these contributions did not differ significantly between SS and SS-13BN
      rats in any wake-sleep state. 5. The data suggest that differences in the central
      and baroreflex contributions to HP control among wake-sleep states, which have
      been demonstrated in SHR, can be generalized to other rat models used in
      hypertension research. Impairments in the baroreflex and central autonomic
      control of HP during quiet wakefulness and REMS, respectively, cannot be
      generalized as an index of genetic susceptibility to hypertension.

PMID- 19769609
TI  - (Pro)renin receptor contributes to diabetic nephropathy by enhancing renal
      inflammation.
AB  - 1. (Pro)renin receptor (PRR) binding to renin or prorenin mediates angiotensin
      (Ang) II-dependent and -independent effects. Expression of the PRR is increased
      in kidneys of diabetic rats, but its role in diabetic nephropathy is unknown. In
      the present study, we investigated the contribution of the PRR to the development
      of diabetic nephropathy through enhancement of renal production of tumour
      necrosis factor (TNF)-alpha and interleukin (IL)-1beta. 2. Normoglycaemic control
      and streptozotocin-diabetic Sprague-Dawley rats were used in the study. The urine
      albumin : creatinine ratio (UACR), renal interstitial fluid (RIF) levels of
      AngII, TNF-alpha and IL-1beta and renal expression of TNF-alpha and IL-1beta were
      evaluated in control, untreated diabetic and diabetic rats treated with either a
      PRR blocker (PRRB; 0.2 mg/kg per day NH3-RILLKKMPSV-COOH), the AT(1) receptor
      antagonist valsartan (2 mg/kg per day) or combined therapy, administered directly
      into the renal cortical interstitium for 14 days via osmotic minipumps. 3.
      Compared with values in normoglycaemic control rats, UACR and RIF AngII, TNF
      alpha and IL-1beta were significantly higher in untreated diabetic rats.
      Treatment of diabetic rats with the PRRB or valsartan alone and in combination
      significantly reduced UACR and RIF TNF-alpha and IL-1beta levels. Renal
      expression of TNF-alpha and IL-1beta was higher in untreated diabetic rats than
      in control rats, but was reduced significantly following treatment with PRRB or
      valsartan alone and in combination. Renal PRR expression was increased in
      untreated and PRRB-treated diabetic rats and reduced in rats receiving valsartan
      alone or combination therapy. The PRRB had no effect on RIF AngII levels, whereas
      valsartan alone and in combination with the PRRB significantly increased AngII
      levels. 4. In conclusion, the PRR is involved in the development and progression
      of kidney disease in diabetes by enhancing renal production of the inflammatory
      cytokines TNF-alpha and IL-1beta, independent of renal AngII effects.

PMID- 19769610
TI  - Lowering of blood pressure during chronic suppression of central sympathetic
      outflow: insight from computer simulations.
AB  - 1. Chronic electrical stimulation of the carotid sinuses has provided unique
      insight into the mechanisms that cause sustained reductions in blood pressure
      during chronic suppression of central sympathetic outflow. 2. Because renal
      denervation does not abolish the sustained fall in arterial pressure in response
      to baroreflex activation, this observation has seemingly challenged the concept
      that the kidneys play a critical role in the long-term control of arterial
      pressure during chronic changes in sympathetic activity. The aim of the present
      study was to use computer simulations to provide a more comprehensive
      understanding of physiological mechanisms that mediate sustained reductions in
      arterial pressure during prolonged baroreflex-mediated suppression of central
      sympathetic outflow. 3. Physiological responses to baroreflex activation under
      different conditions were simulated by an established mathematical model of human
      physiology (QHP2008; see Supporting Information (Appendix S1) provided in the
      online version of this article and/or
      http://groups.google.com/group/modelingworkshop). The model closely reproduced
      empirical data, providing important validation of its accuracy. 4. The
      simulations indicated that baroreflex-mediated suppression of renal sympathetic
      nerve activity does chronically increase renal excretory function but that, in
      addition, hormonal and haemodynamic mechanisms also contribute to this
      natriuretic response. The contribution of these redundant natriuretic mechanisms
      to the chronic lowering of blood pressure is of increased importance when
      suppression of renal adrenergic activity is prevented, such as after renal
      denervation. Activation of these redundant natriuretic mechanisms occurs at the
      expense of excessive fluid retention. 5. More broadly, the present study
      illustrates the value of numerical simulations in elucidating physiological
      mechanisms that are not obvious intuitively and, in some cases, not readily
      testable in experimental studies.

PMID- 19769611
TI  - Stroke in China.
AB  - 1. Following rapid economic development in China, the epidemiological
      characteristics, management and prevention strategies for stroke are changing. In
      the present article, we review recent epidemiological data, as well as studies
      into the management and prevention of stroke in China. 2. The main findings of
      the studies reviewed suggest that stroke mortality in China has been reduced
      significantly. The percentage of haemorrhagic strokes in China is significantly
      higher than that reported in Western countries. The incidence and subtype of
      stroke varied widely in different regions in China. Some of the modifiable risk
      factors for stroke are on the increase in China, including hypertension. 3.
      Management of stroke is slowly being developed and standardized, as evidenced by
      the establishment of stroke units and improvements in emergency care. Studies on
      primary and secondary stroke prevention remain insufficient. Well-designed
      epidemiological surveys and clinical trials for stroke prevention and management
      are urgently needed in China.

PMID- 19769612
TI  - Hydrogen sulphide protects H9c2 cells against chemical hypoxia-induced injury.
AB  - 1. The aim of the present study was to investigate the effect of hydrogen
      sulphide (H(2)S) on cobalt chloride (CoCl(2))-induced injury in H9c2 embryonic
      rat cardiac cells. 2. After 36 h incubation in the presence of 600 micromol/L
      CoCl(2), reduced cell viability of H9c2 cells was observed, as well as the
      induction of apoptosis. In addition, CoCl(2) (600 micromol/L) enhanced the
      production of reactive oxygen species (ROS) and the expression of cleaved caspase
      3, induced a loss of mitochondrial membrane potential (MMP) and decreased reduced
      glutathione (GSH) production. These results suggest that CoCl(2) induces similar
      responses to hypoxia/ischaemia. 3. Pretreatment of cells with 400 micromol/L NaHS
      (a H(2)S donor) for 30 min prior to exposure to CoCl(2) (600 micromol/L)
      significantly protected H9c2 cells against CoCl(2)-induced injury. Specifically,
      increased cell viability and decreased apoptosis were observed. In addition, NaHS
      pretreatment blocked the CoCl(2)-induced increases in ROS production and cleaved
      caspase 3 expression, as well as the decreases in GSH production and loss of MMP.
      4. Pretreatment of cells with 2000 micromol/L N-acetylcysteine (NAC), a ROS
      scavenger, for 1 h prior to CoCl(2) exposure significantly protected H9c2 cells
      against CoCl(2)-induced injury, specifically enhancing cell viability, decreasing
      ROS production and preventing loss of MMP. 5. The findings of the present study
      suggest that H(2)S protects H9c2 cells against CoCl(2)-induced injury by
      suppressing oxidative stress and caspase 3 activation.

PMID- 19769613
TI  - Incidence of thyrotoxicosis in childhood: a national population based study in
      the UK and Ireland.
AB  - OBJECTIVE: To measure the UK and Ireland incidence of childhood (<15 years)
      thyrotoxicosis and to describe the presenting features. CONTEXT: Incidence data
      on thyrotoxicosis in childhood are not available for the UK and Ireland. Recent
      studies have reported an apparent increase in cases in Europe. DESIGN: A national
      prospective surveillance study for 12 months from September 2004, co-ordinated by
      The British Paediatric Surveillance Unit (BPSU). PATIENTS AND MEASUREMENTS: All
      paediatricians across the UK and Ireland were requested monthly to report new
      cases. Details of presenting features were then obtained by questionnaire.
      RESULTS: One hundred ten cases of acquired childhood thyrotoxicosis were
      identified in the UK and Ireland. The incidence of acquired thyrotoxicosis was
      0.9 per 100,000 <15 years olds in the UK and Ireland, (95% CI: 0.8-1.1).
      Autoimmune thyrotoxicosis accounted for 96% of cases. There was an increasing
      incidence with age in each sex. Females have a significantly higher incidence
      than males in the 10- to 14-year age group. A variety of presenting symptoms were
      reported: weight loss (64%), fatigue/tiredness (54%), change in behaviour' (50%)
      and heat intolerance (47%). 4.5 % cases were asymptomatic. The commonest signs
      were goitre (78%) and tremor (58%). There were no cases of thyroid storm.
      CONCLUSIONS: This national population survey defines the incidence of
      thyrotoxicosis in children in the UK and Ireland during 2004-2005, which was
      lower than expected in comparison with other European studies. The survey
      illustrates contemporary presenting characteristics of the disease.

PMID- 19769614
TI  - The effect of growth hormone (GH) replacement on muscle strength in patients with
      GH-deficiency: a meta-analysis.
AB  - CONTEXT/OBJECTIVES: GH replacement increases muscle mass and reduces body fat in
      growth hormone deficiency (GHD) adults. A recent meta-analysis has demonstrated
      that this improvement in body composition is associated with improved exercise
      performance. The current meta-analysis was carried out to determine whether high
      quality evidence exists to support a beneficial effect of GH replacement on
      strength. DESIGN/METHODS: An extensive Medline search/literature review
      identified eight studies with utilizable, robust data, involving 231 patients in
      nine cohorts. Previously unpublished data were sought from authors and obtained
      in two cases. All studies included were randomized, double-blind, placebo
      controlled, of parallel or cross-over design and of an average 6.7 months
      duration. Information was retrieved in uniform format, with data pertaining to
      patient numbers, study-design, GH-dose, mean age, IGF-I levels and muscle
      strength measurements (isometric or isokinetic quadriceps strength) recorded.
      Data were analysed using a fixed-effects model, utilizing continuous data
      measured on different scales. A summary effect measure (d(s)) was derived for
      individual strength variables, whereas an overall summary effect was derived from
      the sum of all studies incorporating different variables; 95% CIs were calculated
      from the weighted variances of individual study effects. RESULTS: Analysis
      revealed no significant improvement, neither when all studies were combined (d(s)
      = +0.01 +/- 0.26) nor when measured individually (isometric quadriceps strength,
      d(s) = +0.02 +/- 0.32 and isokinetic quadriceps strength, d(s) = 0.00 +/- 0.45).
      CONCLUSIONS: Evidence from short-term controlled studies fails to support a
      benefit on muscle strength of GH replacement in GHD patients, which is likely to
      occur over a longer time-course, as seen in open-label studies.

PMID- 19769615
TI  - Health status in women with Turner syndrome: a questionnaire study on health
      status, education, work participation and aspects of sexual functioning.
AB  - CONTEXT: Turner syndrome (TS) is a complex medical condition with specific
      cognitive and psychosocial characteristics and frequent medical morbidity. Few
      studies have investigated the influence this has on health status, education and
      ability to work. OBJECTIVE: To explore health status, level of education, work
      participation, medical conditions, physical activity, satisfaction with life and
      aspects of sexual functioning in adult TS women and compare with a matched
      control group. DESIGN: A questionnaire was sent to 168 adult women with TS >18
      years registered in a database of Frambu Resource Centre for Rare Disorders and
      The TS Association in Norway. We assessed health status with Short Form 36,
      education with Norwegian Standard Classification of Education, and employment
      with The General Nordic Questionnaire. Life satisfaction was measured with LiSat
      9, and questions on psychological strain during life phases were included.
      RESULTS: Eighty women with TS (34.0 +/- 11.7 years) and 214 controls (32.9 +/-
      10.6) responded. The TS group reported significantly more health problems and
      impaired health status in the two subscales "physical functioning" and "general
      health" (P < 0.001). Level of education and work participation was similar among
      TS and controls. TS moved away from their parents' home later than controls (20.4
      +/- 4.0 vs. 18.7 +/- 2.1, P = 0.001). Age at sexual debut differed significantly
      (21.2 +/- 4.3 vs. 17.3 +/- 2.4 years, P < 0.001). CONCLUSION: TS attains the same
      level of education and level of employment as controls, they report more frequent
      occurrence of medical conditions, but scored lower on only two subscales in the
      SF-36. Despite considerable medical morbidity, TS seem to cope well with life.

PMID- 19769616
TI  - Adrenal vein sampling for Primary Aldosteronism: time for a reality check.

PMID- 19769617
TI  - Association of sex hormones and C-reactive protein levels in men.
AB  - OBJECTIVES: The age-associated decline in sex hormone levels in men is paralleled
      by an increase in cardiovascular disease and associated risk factors including
      low grade chronic inflammation. The objective of this analysis was to investigate
      the association between sex hormone levels and C-reactive protein (CRP) in a
      population-based sample of men. DESIGN: Population-based, cross-sectional
      observational survey. PARTICIPANTS: A multistage stratified design was used to
      recruit a random sample of 2301 racially and ethnically diverse men age 30-79
      years. Blood samples were obtained on 1899 men. Analyses were conducted on 1559
      men with complete data on CRP and sex hormone levels. MEASUREMENTS: High
      sensitivity CRP levels. The association between CRP and sex hormone levels was
      assessed using multiple linear regression models. RESULTS: An inverse association
      was observed, in both bivariate and multivariate analyses, between CRP and total
      testosterone, free testosterone and SHBG levels. These associations remained
      statistically significant after adjusting for age, body mass index, comorbid
      conditions and lifestyle factors. A positive trend between oestradiol (total and
      free) and CRP levels was not statistically significant. CONCLUSIONS: A robust,
      inverse dose-response correlation between testosterone and SHBG levels with CRP
      levels provides further evidence of a potential role of androgens in inflammatory
      processes.

PMID- 19769618
TI  - Hypothalamic-pituitary-adrenal (HPA) axis functioning in relation to body fat
      distribution.
AB  - OBJECTIVE: To relate hypothalamic-pituitary-adrenal (HPA) axis functioning and
      HPA feedback functioning to body fat distribution in normal weight to obese
      subjects. PATIENTS: 91 men and 103 women [age 18-45 years, BMI 19-35 kg/m(2),
      waist-to-hip ratio (WHR) 0.6-1.1]. MEASUREMENTS: Anthropometry, body composition
      using hydrodensitometry and deuterium dilution method, cortisol variability by
      measuring 5-h cortisol concentrations, HPA axis feedback functioning using a
      dexamethasone suppression test, and HPA axis functioning under a challenged
      condition consisting of a standardized high-intensity test with ingestion of 4 mg
      dexamethasone. RESULTS: In men, an inverse relationship was observed between 5-h
      cortisol exposure (nmol/ml) and fat mass index (FMI) (kg/m(2)) (r = -0.55, P <
      0.001). In women, relationships were observed between 5-h cortisol exposure
      (nmol/ml.min) and WHR (r = -0.49, P < 0.001), maximal workload (r = 0.32, P <
      0.001) as well as oral contraceptive use (r = 0.38, P < 0.001). Similarly, in
      men, an inverse relationship was observed between negative feedback expressed as
      baseline concentrations minus post dexamethasone cortisol concentrations
      (nmol/ml) and FMI (r = -0.53, P < 0.001). In women, relationships were observed
      between negative feedback expressed as baseline concentrations minus post
      dexamethasone cortisol concentrations (nmol/ml) and WHR (r = -0.43, P < 0.001),
      maximal workload (r = 0.30, P < 0.001) as well as oral contraceptive use (r =
      0.43, P < 0.001) in women. Moreover, an inverse relationship was observed between
      HPA axis functioning in a challenged condition expressed as percentage increase
      of cortisol concentrations after standardized high-intensity test with ingestion
      of 4 mg dexamethasone (%) and waist circumference (r = -0.21, P < 0.10) in men
      and WHR (r = -0.21, P < 0.05) in women. In men, strong positive relationships
      were observed between FMI and waist circumference (r = 0.85, P < 0.001), as well
      as waist-to-hip ratio (r = 0.70, P < 0.001). CONCLUSION: Disturbance of HPA axis
      functioning under basal and challenged conditions is related to visceral fat
      accumulation.

PMID- 19769619
TI  - Levothyroxine in subclinical hypothyroidism: a lifelong therapy?

PMID- 19769620
TI  - Association between androgens, intima-media thickness and the metabolic syndrome
      in obese adolescent girls.
AB  - BACKGROUND: While an association between androgens and the metabolic syndrome
      (MS) is well established in obese women, studies concerning this relationship are
      scarce in obese adolescent girls. Therefore, we analysed the relationships
      between androgens, MS and intima-media thickness (IMT) in this age-group.
      METHODS: In 160 obese girls (aged 12-18 years, mean BMI: 32.6 +/- 5.0 kg/m((2))),
      androgens [testosterone, dehydroepiandrosterone sulphate (DHEA-S),
      androstenedione], SHBG and the components of MS (waist circumference, blood
      pressure (BP), lipids, uric acid, insulin, glucose, 2 h glucose in oral glucose
      tolerance test (oGTT)) were studied. Furthermore, IMT was determined in a
      subgroup of 71 randomly chosen girls. RESULTS: Testosterone correlated
      significantly to systolic BP (r = 0.20), diastolic BP (r = 0.24), 2 h glucose in
      oGTT (r = 0.30), triglycerides (r = 0.19), uric acid (r = 0.17), waist
      circumference (r = 0.25) and IMT (r = 0.54). These relationships (except for
      waist circumference and uric acid) were independent of BMI and insulin resistance
      index homeostasis model assessment. In contrast to testosterone, DHEA-S,
      androstenedione and SHBG showed no or weaker correlations to any parameter of MS.
      The 48 girls with MS demonstrated significantly higher testosterone (1.8 +/- 0.7
      nmol/l; P = 0.025) and DHEA-S (4.7 +/- 2.3 micromol/l; P = 0.008) concentrations
      as compared with the 112 girls without MS (mean testosterone 1.5 +/- 0.7 nmol/l,
      mean DHEA-S 3.6 +/- 2.3 micromol/l). CONCLUSIONS: Testosterone was significantly
      related to MS and its components in obese adolescent girls independently of BMI
      and insulin resistance. As IMT was significantly associated with testosterone,
      this supports the clinical relevance of this finding.

PMID- 19769621
TI  - Adipokines in type 1 diabetes after successful pancreas transplantation: normal
      visfatin and retinol-binding-protein-4, but increased total adiponectin fasting
      concentrations.
AB  - OBJECTIVE: In type 1 diabetes mellitus (T1DM), the release of many hormones, not
      only from beta-cells, but also from adipocytes (adipokines) may be altered. After
      successful pancreas-kidney-transplantation (PKTx), T1DM patients can revert to a
      nondiabetic metabolism, but it is unclear whether alterations of adipokines are
      still present after PKTx. DESIGN, PATIENTS AND MEASUREMENTS: Concentrations of
      adipokines [visfatin, retinol-binding protein-4 (RBP-4), adiponectin, high
      molecular weight (HMW) adiponectin] were measured at fasting in 10 PKTx and in 19
      T1DM. Nondiabetic healthy controls (CON, n = 9) and six nondiabetic patients
      after kidney transplantation (KTx) were examined as control groups. In PKTx, KTx
      and CON, indices of insulin sensitivity (OGIS) and beta cell function (adaptation
      index, AI) were calculated from 75 g oral glucose tolerance test (OGTT) data.
      RESULTS: Fasting serum visfatin (T1DM: 56 +/- 4 microg/l, PKTx: 42 +/- 6
      microg/l, KTx: 39 +/- 3 microg/l, CON: 40 +/- 3 microg/l) and RBP-4 (T1DM: 490 +/
      26 microg/l, PKTx: 346 +/- 39 microg/l, KTx: 401 +/- 13 microg/l, CON: 359 +/-
      36 microg/l) was increased by 40% and 36%, respectively (each P < 0.03) in T1DM
      only. Levels were positively correlated with HbA1c in all subjects (visfatin: r =
      0.43, P < 0.004; RBP-4: r = 0.46, P < 0.03). Fasting plasma adiponectin was 80%
      higher in T1DM and in PKTx (T1DM: 18 +/- 2 mg/l, PKTx: 18 +/- 3 mg/l, KTx: 12 +/-
      3 mg/l, CON: 10 +/- 1 mg/l; P < 0.04) and was positively correlated with diabetes
      duration (r = 0.37, P < 0.02). HMW/total adiponectin ratio was increased in T1DM
      (P < 0.02). PKTx displayed a normoglycaemic metabolism as insulin sensitive as
      CON, but AI was lower than in CON and KT (P < 0.01). CONCLUSIONS: T1DM after
      successful PKTx show normal fasting visfatin and RBP-4 levels and HMW
      adiponectin/adiponectin-ratio, which are elevated in T1DM, whereas total
      adiponectin levels are similarly increased in T1DM and PKTx patients.

PMID- 19769622
TI  - Growth in foetal life and infancy is associated with abdominal adiposity at the
      age of 2 years: the generation R study.
AB  - OBJECTIVE: Early weight gain is associated with an increased risk of obesity. It
      is not known whether rapid weight gain in foetal life and infancy is also
      associated with increased abdominal adiposity. We examined the associations of
      foetal and postnatal growth characteristics with abdominal fat mass at the age of
      2 years. DESIGN: This study was performed in 481 children participating in a
      prospective cohort study from early foetal life onward. MEASUREMENTS: Foetal and
      postnatal growth characteristics in second and third trimester, at birth and at
      the age of 2 years were related to abdominal fat mass (subcutaneous distance and
      area, preperitoneal distance and area) measured by ultrasound at the age of 2
      years. RESULTS: Foetal and birth weight were not associated with abdominal
      subcutaneous fat mass. Estimated foetal weight in second trimester of pregnancy
      was inversely associated with preperitoneal fat area [-3.73% (95% confidence
      interval -7.23, -0.10)] per standard deviation score increase in weight. Weight
      gain from birth to the age of 2 years was positively associated with
      preperitoneal fat mass measures. These associations remained significant after
      adjustment for age, sex, breastfeeding and body mass index. Positive associations
      were found between catch-up growth in weight and abdominal fat mass measures.
      CONCLUSIONS: Our results suggest that rapid growth rates during foetal life and
      infancy are associated with increased abdominal subcutaneous and preperitoneal
      fat mass in healthy children. Further studies need to explore whether these
      associations persist in later life and are related to metabolic syndrome
      outcomes.

PMID- 19769623
TI  - Ascites from patients with alcoholic liver cirrhosis contains higher IGF-I
      bioactivity than serum.
AB  - OBJECTIVE: Patients with liver cirrhosis have diminished hepatic IGF-I
      generation, resulting in low circulating levels, whereas data on IGF-I in ascites
      are sparse. Therefore, we compared the IGF-system in serum and ascites from
      cirrhotic patients. DESIGN AND PATIENTS: The study comprised 43 patients (12
      females) with ascites and liver function of 58 +/- 10% of normal. Serum and
      ascites were collected concomitantly in the fasting state. In 11 patients, second
      serum and ascitic samples were collected within the first week. Eleven matched
      controls were also included. All samples were assayed for IGF-related parameters
      by immunoassays and by cell-based IGF-I bioassay. RESULTS: As compared with
      controls, serum total IGF-I, total IGF-II, pro-IGF-II and bioactive IGF-I were
      reduced in liver patients, whereas IGF-binding protein 1 (IGFBP-1), IGFBP-2 and
      the soluble IGF-II receptor were elevated (P < 0.005 for all). In ascites, all
      IGF-related peptides but pro-IGF-II were further reduced as compared with serum
      (P < 0.001). By contrast, bioactive IGF-I was fourfold elevated in ascites as
      compared with serum (2.20 +/- 0.33 vs. 0.55 +/- 0.08 microg/l, P < 0.001). In
      ascites, the IGF-I bioactivity signal was completely blocked by addition of IGFBP
      3. Repetitive measurements (n = 11) in ascites showed that all peptides but IGFBP
      1 remained unchanged within 1 week. CONCLUSIONS: It is a novel observation that
      the in vitro bioactivity of IGF-I can be higher in fluids from an extravascular
      compartment than in serum, in contrast to immunoreactive levels. This supports
      different roles for endocrine and paracrine/autocrine IGF-I, but the
      pathophysiological significance of our observation remains to be clarified.

PMID- 19769624
TI  - Effects of octreotide exposure during pregnancy in acromegaly.
AB  - BACKGROUND: Only six women who were treated with somatostatin analogues (SSAs)
      throughout their pregnancies have been described so far. The influence of SSAs on
      the course of pregnancy and newborn outcomes remains largely unknown. Many
      aspects of SSAs pharmacokinetics in mother and foetus have not yet been defined.
      METHODS AND FINDINGS: We report a case study on the effects of octreotide on
      uterine artery blood flow, octreotide concentrations in biological fluids of
      mother and newborn, and somatostatin (SST) receptor expression and binding at the
      level of the maternal-foetal barrier tissues in an acromegalic woman treated with
      short-acting octreotide throughout her pregnancy. An acute decrease in uterine
      artery blood flow was observed after octreotide injections, without affecting the
      pregnancy course, delivery, or foetal development. Octreotide concentrations were
      high in maternal serum and colostrum and lower in umbilical cord serum, amniotic
      fluid, and newborn serum. All SST receptor subtypes can be expressed in placental
      tissue but their binding profile was weak both in the placenta and umbilical
      cord. The child was healthy and developed normally up to age 6 from an
      anthropometric, metabolic, and endocrine point of view. We reviewed all published
      reports on pregnancy SSA exposure and outcomes were compared to a time-matched
      group of acromegalic women not exposed to SSA. No significant effect on the
      mother or foetus was observed. CONCLUSIONS: Short-acting octreotide appears not
      to affect the function of the maternal-foetal barrier or foetal development,
      except for the occurrence of acute, reversible, and clinically irrelevant
      haemodynamic changes. These data support the feasibility and safety of treatment
      with short-acting octreotide in acromegalic women during pregnancy and excludes
      major matters of concern about the effects of this medication on pregnancy itself
      and its outcome.

PMID- 19769625
TI  - New imaging approaches to phaeochromocytomas and paragangliomas.

PMID- 19769628
TI  - Comment on: anatomical branches of the superior rectal artery in the distal
      rectum.

PMID- 19769629
TI  - A letter in response to rectal cancer: involved CRM - a root cause analysis.

PMID- 19769630
TI  - Arsenic trioxide and cisplatin synergism increase cytotoxicity in human ovarian
      cancer cells: therapeutic potential for ovarian cancer.
AB  - Drug resistance is a major concern in the successful treatment of ovarian cancer.
      In the present study we report a combinational drug regime using arsenic trioxide
      (ATO) and cisplatin (CDDP) to increase therapeutic potentiality in ovarian cancer
      cells. ATO-mediated growth inhibition and apoptosis in human suspension ovarian
      cancer COC1 cells were evaluated by MTT assay and annexin V assay using flow
      cytometry, respectively. cDNA arrays were performed to screen ATO-mediated gene
      expression. Treatment of COC1 cells with ATO alone resulted in growth inhibition
      and apoptosis with a dose-and time-dependent fashion; further cDNA arrays showed
      that 34 genes (23 up-regulated genes and 11 down-regulated genes) may strongly
      associate with the antiproliferative and pro-apoptotic effects induced by ATO.
      Furthermore, Chou-Talalay analysis was used to evaluate the combinational effect
      of ATO and CDDP as well as dose-reduction index (DRI) in a panel of ovarian
      cancer cells including CDDP-sensitive and -resistant cell lines. The combination
      index (CI) analysis indicated that the interaction effect of ATO/CDDP exhibited a
      wide range of synergism in all the adherent ovarian cancer cells (A2780, IGROV-1,
      SKOV-3, and R182) as well as 0.93 to 0.69 for IC(50) to IC(90) in suspension COC1
      cells where CI < 1, =1, and >1, define synergism, additive effect, and
      antagonism, respectively. More intriguingly, the combination of ATO and CDDP
      yielded favorable DRIs ranging from 1.23-fold to 13.51-fold dose reduction. These
      results suggest that ATO and its combination with CDDP present therapeutic
      potential for ovarian cancer, and deserve further preclinical and clinical
      studies.

PMID- 19769631
TI  - 5-Methoxypsoralen plus ultraviolet (UV) A is superior to medium-dose UVA1 in the
      treatment of severe atopic dermatitis: a randomized crossover trial.
AB  - BACKGROUND: Ultraviolet (UV) A1 and psoralen plus UVA (PUVA) are effective
      treatment options for severe atopic dermatitis (AD); however, their relative
      efficacy has not yet been determined in a head-to-head study. OBJECTIVES: To
      compare UVA1 and oral 5-methoxypsoralen (5-MOP) plus UVA with respect to
      efficacy, tolerability and duration of response in patients with severe
      generalized AD. METHODS: Forty patients were included in this randomized observer
      blinded crossover trial. The patients received either 15 exposures to medium-dose
      UVA1 as the first treatment and, in cases of relapse, another 15 exposures to 5
      MOP plus UVA as the second treatment, or vice versa. All patients were followed
      until 12 months after discontinuation of the last treatment. The SCORAD score was
      determined by a blinded investigator at baseline, after 10 and 15 treatments each
      and during the follow-up period. In addition, all adverse events were recorded
      during the whole study period. RESULTS: Twenty-three patients completed the
      crossover treatment. Both phototherapies resulted in clinical improvement;
      however, PUVA reduced the baseline SCORAD score to a significantly greater extent
      than UVA1 (mean +/- SD 54.3 +/- 25.7% vs. 37.7 +/- 22.8%; P = 0.041). The median
      length of remission was 4 weeks (interquartile range 4-12) after UVA1 and 12
      weeks (interquartile range 4-26) after PUVA therapy (P = 0.012). CONCLUSIONS:
      PUVA provides a better short- and long-term response than medium-dose UVA1 in
      patients with severe AD.

PMID- 19769632
TI  - Angiogenic and prothrombotic markers in extensive slow-flow vascular
      malformations: implications for antiangiogenic/antithrombotic strategies.
AB  - BACKGROUND: Venous and combined malformations are slow-flow haemodynamically
      inactive lesions that are present at birth and worsen slowly with advancing age,
      showing no tendency towards involution. The pathogenesis of vascular anomalies
      has not been fully elucidated, but their formation and progression are closely
      related to angiogenesis. Localized intravascular coagulation associated with
      venous or combined malformations is characterized by low fibrinogen, high D
      dimers, and normal platelet count. OBJECTIVES: To assess the relationship of
      angiogenic factors with prothrombotic and endothelial damage/dysfunction markers
      in patients with extensive slow-flow vascular malformations. METHODS: A 2-year
      study (2005-2007) included 31 consecutive patients with extensive slow-flow
      vascular malformations from one centre. RESULTS: Serum levels of the endothelial
      receptor tyrosine kinase TIE-2, matrix metalloproteinase (MMP)-9 and angiopoietin
      (Ang)-2 and plasma levels of D-dimer, plasminogen activator inhibitor type 1 (PAI
      1), tissue-type plasminogen activator and von Willebrand factor (vWf) were
      significantly increased in patients compared with healthy controls, whereas serum
      levels of vascular endothelial growth factor (VEGF)-C, VEGF-D, MMP-2, Ang-1,
      platelet-derived growth factor (PDGF)-AB and PDGF-BB were significantly decreased
      in patients compared with controls. A strong positive correlation was present
      between Ang-1 and PDGF-AB levels (r = 0.63, P < 0.001), between PDGF-AB and PDGF
      BB levels (r = 0.67, P < 0.001), and between fibrinogen and PAI-1 levels (r =
      0.41, P = 0.031). A strong negative correlation was present between Ang-1 and vWf
      levels (r = -0.48, P = 0.006), between D-dimer and fibrinogen levels (r = -0.71,
      P < 0.001), and between PDGF-AB and vWf levels (r = -0.42, P = 0.017).
      CONCLUSIONS: These findings suggest that angiogenic, coagulation and endothelial
      damage/dysfunction markers are possibly linked in pathogenesis of extensive slow
      flow vascular malformations, and might have therapeutic implications.

PMID- 19769633
TI  - Systematic review: caspase-cleaved fragments of cytokeratin 18 - the promises and
      challenges of a biomarker for chronic liver disease.
AB  - BACKGROUND: Biomarkers hold great promise for detecting chronic liver disease
      without the use of liver biopsy. AIM: To review the usefulness of cytokeratin
      (CK) 18 fragments, a marker of hepatocyte apoptosis, to predict the presence of
      chronic liver injury. METHODS: Available literature identified from PubMed was
      reviewed. RESULTS: Levels of CK18 fragments have been shown to be elevated in
      hepatocellular carcinoma, viral hepatitis, alcoholic hepatitis, nonalcoholic
      fatty liver disease and cholestatic liver disease. In the setting of nonalcoholic
      fatty liver disease, CK18 fragments may distinguish nonalcoholic steatohepatitis
      from simple fatty liver. CONCLUSIONS: Undoubtedly, the most promising application
      of CK18 fragments is currently in nonalcoholic fatty liver disease, and
      especially for distinguishing patients with nonalcoholic steatohepatitis vs.
      those with simple steatosis. Further investigations and technical improvements
      are required to cross the boundary from research to the clinical application of
      CK18 fragments as a marker of chronic liver disease.

PMID- 19769634
TI  - Clinical trial: the efficacy and safety of routine bowel cleansing agents for
      elective colonoscopy in persons with spinal cord injury - a randomized
      prospective single-blind study.
AB  - BACKGROUND: As difficulty with evacuation is a common occurrence in individuals
      with spinal cord injury, preparation prior to colonoscopy may be suboptimal and,
      perhaps, more hazardous. AIM: To assess the safety and efficacy of bowel
      cleansing regimens in persons with spinal cord injury. METHODS: Randomized,
      prospective, single blind study comparing polyethylene glycol (PEG), oral sodium
      phosphosoda (OSPS) and combination of both for colonic preparation prior to
      colonoscopy in subjects with spinal cord injury. RESULTS: Thirty six subjects
      with eGFR > or =60 mL/min/1.73 m(2) were randomized to PEG or OSPS or PEG+OSPS.
      Regardless of bowel preparation employed, >73% of subjects had unacceptable
      colonic cleansing. No subject in the OSPS preparation group demonstrated a
      decrease in eGFR or an increase in serum creatinine concentration from the
      baseline. OSPS and PEG+OSPS preparations caused a transient change in serum
      potassium, phosphate and calcium concentrations, but no change in electrolytes
      was noted in the PEG group. CONCLUSIONS: Neither OSPS alone, PEG alone nor their
      combination was sufficient to prepare adequately the bowel for colonoscopy in
      most patients with spinal cord injury. However, administration of OSPS and/or PEG
      appears to be safe in the spinal cord injury population, provided adequate
      hydration is provided.

PMID- 19769635
TI  - Orexins (hypocretins) actions on the GHRH/somatostatin-GH axis.
AB  - The secretion of growth hormone (GH) is regulated through a complex
      neuroendocrine control system that includes two major hypothalamic regulators,
      namely GH-releasing hormone (GHRH) and somatostatin (SST) that stimulate and
      inhibit, respectively, GH release. Classical experiments involving damage and
      electrical stimulation suggested that the lateral hypothalamic area (LHA)
      modulated the somatotropic axis, but the responsible molecular mechanisms were
      unclear. Evidence obtained during the last decade has demonstrated that
      orexins/hypocretins, a family of peptides expressed in the LHA controlling
      feeding and sleep, play an important regulatory role on GH, by inhibiting its
      secretion modulating GHRH and SST neurones. Considering that GH release is
      closely linked to the sleep-wake cycle and feeding state, understanding
      orexin/hypocretin physiology could open new therapeutic possibilities in the
      treatment of sleep, energy homeostasis and GH-related pathologies, such as GH
      deficiency.

PMID- 19769636
TI  - The decrease in electrically evoked force production is delayed by a previous
      bout of stretch-shortening cycle exercise.
AB  - AIM: Unaccustomed physical exercise with a large eccentric component is
      accompanied by muscle damage and impaired contractile function, especially at low
      stimulation frequencies. A repeated bout of eccentric exercise results in less
      damage and improved recovery of contractile function. Here we test the hypotheses
      that (1) a prior stretch-shortening cycle (SSC) exercise protects against
      impaired muscle function during a subsequent bout of SSC exercise and (2) the
      protection during exercise is transient and becomes less effective as the
      exercise progresses. METHODS: Healthy untrained men (n = 7) performed SSC
      exercise consisting of 100 maximal drop jumps at 30 s intervals. The same
      exercise was repeated 4 weeks later. Peak quadriceps muscle force evoked by
      electrical stimulation at 15 (P15) and 50 (P50) Hz was measured before exercise,
      after 10, 25, 50 and 100 jumps as well as 1 and 24 h after exercise. RESULTS: P15
      and P50 were higher during the initial phase of the repeated bout compared with
      the first exercise bout, but there was no difference between the bouts at the end
      of the exercise periods. P15 and P50 were again larger 24 h after the repeated
      bout. The P15/P50 ratio during exercise was not different between the two bouts,
      but it was higher after the repeated bout. CONCLUSION: A prior bout of SSC
      exercise temporarily protects against impaired contractile function during a
      repeated exercise bout. The protection can again be seen after exercise, but the
      underlying mechanism then seems to be different.

PMID- 19769637
TI  - Potassium-transporting proteins in skeletal muscle: cellular location and fibre
      type differences.
AB  - Abstract Potassium (K(+)) displacement in skeletal muscle may be an important
      factor in the development of muscle fatigue during intense exercise. It has been
      shown in vitro that an increase in the extracellular K(+) concentration
      ([K(+)](e)) to values higher than approx. 10 mm significantly reduce force
      development in unfatigued skeletal muscle. Several in vivo studies have shown
      that [K(+)](e) increases progressively with increasing work intensity, reaching
      values higher than 10 mm. This increase in [K(+)](e) is expected to be even
      higher in the transverse (T)-tubules than the concentration reached in the
      interstitium. Besides the voltage-sensitive K(+) (K(v)) channels that generate
      the action potential (AP) it is suggested that the big-conductance Ca(2+)
      dependent K(+) (K(Ca)1.1) channel contributes significantly to the K(+) release
      into the T-tubules. Also the ATP-dependent K(+) (K(ATP)) channel participates,
      but is suggested primarily to participate in K(+) release to the interstitium.
      Because there is restricted diffusion of K(+) to the interstitium, K(+) released
      to the T-tubules during AP propagation will be removed primarily by reuptake
      mediated by transport proteins located in the T-tubule membrane. The most
      important protein that mediates K(+) reuptake in the T-tubules is the Na(+),K(+)
      ATPase alpha(2) dimers, but a significant contribution of the strong inward
      rectifier K(+) (Kir2.1) channel is also suggested. The Na(+), K(+), 2Cl(-) 1
      (NKCC1) cotransporter also participates in K(+) reuptake but probably mainly from
      the interstitium. The relative content of the different K(+)-transporting
      proteins differs in oxidative and glycolytic muscles, and might explain the
      different [K(+)](e) tolerance observed.

PMID- 19769638
TI  - Dose-response studies for pituitary and testicular function in male dogs treated
      with the GnRH superagonist, deslorelin.
AB  - We tested the effect of dose of GnRH superagonist on pituitary and testicular
      function in a study with four groups of four male dogs. The Controls received
      blank implants and the other three groups received implants containing 3, 6 or 12
      mg deslorelin (D-Trp6-Pro9-des-Gly10-GnRH ethylamide). In all deslorelin-treated
      groups, there was initially an acute increase in plasma concentrations of LH and
      testosterone, followed by declines such that both hormones became undetectable
      after approximately 12 days. There was a dose-response in some of these early
      aspects of the hormone profiles. With respect to long-term effects of treatment,
      the 12-mg dose had significantly greater effects than the smaller doses for the
      duration of minimum testicular volume [366 +/- 77, mean +/- SEM (3 mg), 472 +/-
      74 (6 mg), and 634 +/- 59 (12 mg) days], absence of ejaculate [416 +/- 88 (3 mg),
      476 +/- 83 (6 mg), and 644 +/- 67 (12 mg) days], undetectable plasma
      concentrations of LH and testosterone [367 +/- 64 (3 mg), 419 +/- 72 (6 mg), and
      607 +/- 69 (12 mg) days], the delay until complete recovery of LH and
      testosterone secretion [394 +/- 65 (3 mg), 484 +/- 72 (6 mg) and 668 +/- 47 (12
      mg) days], and the delay until testes had regrown to normal volume [408 +/- 77 (3
      mg), 514 +/- 74 (6 mg), 676 +/- 59 (12 mg) days]. The time taken to restore full
      ejaculates was also longest for the 12-mg dose: 716 +/- 67 (12 mg) days vs 440 +/
      66 (3 mg) and 538 +/- 83 (6 mg) days after implantation. There was no
      correlation between delay to recovery of normal ejaculate quality and body mass.
      We conclude that the dose-response relationship with deslorelin implants is not
      expressed with respect to the degree of suppression of reproduction, but on the
      maximum duration of suppression and thus to delay until recovery.

PMID- 19769639
TI  - Cervical ripening and parturition in cows are driven by a cascade of pro
      inflammatory cytokines.
AB  - The final stages of cervical ripening and parturition resemble an inflammatory
      process. Although the role of cytokines in both spontaneous and experimentally
      induced parturitions has been described in several small laboratory animals and
      humans, the involvement of pro-inflammatory and regulatory cytokines in
      physiologic parturition in cows has not been determined. In this study, the
      cytokine expression profiles were assessed in bovine cervical tissue at several
      stages of pregnancy and at parturition. Serial biopsy samples of the cervix were
      obtained from 10 cows on day 185 and day 275 of pregnancy (which was on average
      5.4 days before parturition) and at parturition. Messenger RNA expression levels
      of interleukin (IL)-1beta, IL-6, IL-8, IL-10 and tumour necrosis factor
      (TNF)alpha were determined using real-time polymerase chain reaction and the
      number of neutrophils and eosinophils was estimated by Luna and Sirius Red
      staining. At parturition, IL-8 expression had increased 430-fold (p < 0.001) when
      compared with that of the day 185 of pregnancy, large numbers of neutrophils had
      invaded the cervix while eosinophils remained scarce, IL-1beta had increased
      eightfold (p < 0.05) and IL-6 had not changed significantly. Additionally, IL-10
      was increased by 10-fold (p < 0.001) and TNFalpha decreased by 57% (p < 0.05)
      when compared with that of the day 185 of pregnancy. The large increase in
      expression of IL-8, enabling the influx of neutrophils, is indicative of its
      important role in the final stage of cervical ripening and at parturition. As
      previous studies have shown that neutrophils excrete matrix metalloproteinases
      (MMP), this might contribute to softening of the cervix. In contrast, the only
      slightly increased levels of IL-1, steady concentrations of IL-6 and decreased
      TNFalpha, the potential consequences of increased IL-10 expression, indicate that
      final cervical of cows in ripening at term parturition is an inflammatory process
      influenced by regulatory cytokines.

PMID- 19769640
TI  - From boutique to basic: a call for standardised medical education in global
      health.

PMID- 19769641
TI  - Reframing medical education research: let's make the publishable meaningful and
      the meaningful publishable.

PMID- 19769642
TI  - The long case and its modifications: a literature review.
AB  - CONTEXT: This review provides a summary of the published literature on the
      suitability of the long case and its modifications for high-stakes assessment.
      METHODS: Databases related to medicine were searched for articles published from
      2000 to 2008, using the keywords 'long case', 'clinical examinations' and
      'clinical assessment'. Reference lists of review articles were hand-searched.
      Articles related to the objective structured clinical examination were
      eliminated. Research-based articles with hard data were given more emphasis in
      this review than those based on opinion. RESULTS: Eighteen articles were
      identified. The main disadvantage of the long case is its inability to sample the
      curriculum widely, resulting in low reliability. The main advantage of the long
      case is its ability to assess the candidate's overall (holistic) approach to the
      patient. Modifications to the long case attempt to: structure the format and the
      marking scheme; increase the number of examiners; observe the candidate's
      behaviour, and increase the number of cases. CONCLUSIONS: The long case is a
      traditional clinical examination format for the assessment of clinical competence
      and assessment at this level is important. The starting point for the majority of
      recent research on the long case has been an acceptance of its low reliability
      and modifications to the format have been proposed. Further evidence of the
      efficacy of these modifications is required, however, before they can be
      recommended for summative assessment. If further research is to be undertaken on
      the long case, it should focus on finding practicable ways of sampling the
      curriculum widely to increase reliability while maintaining the holistic approach
      towards the patient, which represents the attraction of the long case.

PMID- 19769643
TI  - How medical students demonstrate their professionalism when reflecting on
      experience.
AB  - OBJECTIVES: This paper aims to examine the discourses used by students in a
      formal assessment of their ability to demonstrate professional values when
      reflecting on their experiences. METHODS: We carried out a discourse analysis of
      50 randomly selected essays from a summative assessment undertaken by all five
      year groups of students in one UK medical school. RESULTS: Students were able to
      identify a wealth of relevant examples and to articulate key principles of
      professional practice. They were also able to critique behaviours and draw
      appropriate conclusions for their own intended professional development. Detailed
      textual analysis provided linguistic clues to the depth of apparent reflection:
      recurrent use of rhetorical language with minimal use of first-person
      reflections, lack of analysis of underlying factors, and simplistic views of
      solutions may all indicate students whose ability to learn by reflection on
      experience needs further development. There were also areas in which cohorts as a
      whole appeared to have a limited grasp of the important professional issues being
      addressed. CONCLUSIONS: Assessing written reflections is a useful way of making
      students link their experiences with professional development. The detailed
      analysis of language usage may help to refine marking criteria, and to detect
      students and course components where reflective learning competencies are not
      being achieved.

PMID- 19769644
TI  - Teaching ethics to paediatrics residents: the centrality of the therapeutic
      alliance.
AB  - CONTEXT: Previous research on ethical issues encountered by medical professionals
      in training and practice have presented the thematic content of the cases they
      encounter rather than the activities in which clinicians engage and in which they
      most often encounter ethical issues. We conducted a direct observation study of
      paediatrics residents and their preceptors seeing patients in an out-patient
      general paediatrics clinic. Our objectives were to describe the everyday ethics
      related issues paediatrics residents encounter as they interact with patients.
      Our ultimate goal is to use this knowledge to enhance current efforts to teach
      ethics to paediatrics residents. METHODS: The study team directly observed
      paediatrics residents discussing patients with their faculty preceptors (19 half
      day sessions, 76 hours) in an out-patient general paediatrics clinic located in
      an urban academic medical centre. Each interaction between resident and preceptor
      about a single patient was considered a case for further analysis. RESULTS: A
      total of 247 cases were recorded. Forty-one of the cases were coded as having
      ethics-related content. A constant comparative method of qualitative data
      analysis revealed that residents were most likely to encounter ethical issues
      when engaged in the following activities: (i) maintaining a therapeutic alliance
      with the caregiver (e.g. the parent); (ii) prioritising patient or family needs;
      (iii) adjusting to the power embodied by the role of doctors, and (iv)
      distinguishing suboptimal care from abuse or neglect. In addition, our findings
      indicate that it is through their efforts to maintain the therapeutic alliance
      with the caregivers of their patients that residents engage in and integrate
      three processes: developing their medical knowledge; adhering to professional
      norms, and balancing the power inherent in the doctor's role with their
      responsibility to serve the patient's interests. CONCLUSIONS: Medical faculty
      tasked with teaching ethics to paediatrics residents can utilise the results of
      this project to better target and enhance their ethics education efforts directed
      at residents in the out-patient setting. Future research could further examine
      and test these findings in other clinical settings (e.g. adult general medicine).

PMID- 19769645
TI  - Peer estimation of lack of professionalism correlates with low Conscientiousness
      Index scores.
AB  - CONTEXT: Measures of professionalism in undergraduate medical students are
      generally subjective in nature, and based on limited observations of behaviours
      in observed settings. We have previously described an objective scalar measure of
      conscientiousness over many occasions, and shown that it correlates with
      independent faculty estimates of students' professionalism. In this study we test
      the hypothesis that these measures of conscientiousness relate to independent
      peer estimates of professionalism, and explore the relationships between
      conscientiousness, and gender and educational background. METHODS: Medical
      students in Years 1 and 2 of an undergraduate programme were invited to estimate
      the professionalism of fellow students using a peer nomination approach. The
      correlation with the Conscientiousness Index (CI) for each student receiving
      nominations was explored statistically. Male and female students, from three
      educational backgrounds, were also compared on the basis of their CI scores.
      Developmental properties were considered by comparing Year 2 students' CI scores
      with their corresponding Year 1 performance. RESULTS: There was a statistically
      significant negative correlation between CI scores and nominations for lack of
      professionalism. No differences were observed between male and female students.
      There were occasional differences between students of different educational
      backgrounds, but the sample sizes of some groups were small and we would not wish
      to over-interpret these data. CONCLUSIONS: These results support the use of the
      CI as a scalar, objective potential measure of professionalism, although the
      observations require repetition elsewhere and over an extended period of time in
      order to determine the predictive value of this approach.

PMID- 19769646
TI  - Professionalism Mini-Evaluation Exercise for medical residents in Japan: a pilot
      study.
AB  - CONTEXT: Assessing medical professionalism among medical residents is of great
      importance. The Professionalism Mini-Evaluation Exercise (P-MEX) is a tool for
      assessing professionalism that was developed, tested for reliability and
      validated in Canada. Prior to the present study, no Japanese version of the P-MEX
      had been tested. METHODS: We modified the P-MEX for use in Japan and tested it on
      medical residents in a Japanese teaching hospital. For each resident, eight
      evaluators completed the P-MEX forms. A total of 184 P-MEX forms were completed
      on 23 senior residents. The construct validity of the P-MEX was analysed by
      confirmatory factor analysis through structural equation modelling. The
      reliability of the P-MEX was tested using generalisability theory and a decision
      study. After performing the assessment and providing feedback to the residents,
      we conducted a survey on the residents' perceptions of the assessment. RESULTS:
      Results indicate content and construct validity. A confirmatory factor analysis
      revealed that factor loadings ranged from 0.58 to 0.96, indicating good construct
      validity except for one item (P12: Maintained appropriate boundaries with
      patients and colleagues). Structural equation modelling showed that adding new
      items developed in Japan to the P-MEX provided adequate factor validity. A
      decision study showed confidence intervals sufficiently narrow with as few as 10
      evaluations, slightly more than the eight forms verified in Canada. Most
      residents stated that the items were reasonable and appropriate, the results of
      the assessment were consistent with their own self-evaluation and the assessment
      enhanced their motivation. CONCLUSIONS: Our study demonstrated good evidence of
      adequate reliability and validity of the P-MEX for the assessment of
      professionalism among Japanese residents. Moreover, the addition of new items
      developed in Japan provided adequate factor validity.

PMID- 19769647
TI  - Curriculum reform: a narrated journey.
AB  - OBJECTIVES: Curriculum reform poses significant challenges for medical schools
      across the globe. Understanding the medical educator's personal and lived
      experience of curriculum change is paramount. This paper illustrates the use of
      narrative inquiry as a means of exploring the author's own evolving professional
      identity as a medical educator engaged in planning and leading curriculum reform
      and in understanding the meanings she and other medical educators attribute to
      their roles as agents of change in a medical school. CONTEXT: In 2002 it was
      decided to radically reform a school of medicine's (SoM) traditional 6-year
      medical degree course (converting it to a 5-year, integrated, case-based
      programme). This followed a decade of adverse external reports by the national
      accreditation agency. The 2001 accreditation report was the most significant
      catalyst for change, and drew attention to the School's need for a 'collective
      will' to introduce a series of specific curriculum reforms. To support this
      reform, a new curriculum working group (NCWG) supported by a dedicated medical
      education unit (MEU) was established. In late 2002 the author joined the School
      as the director of that unit. METHODS: This paper draws on a 3-year study which
      captured the stories of the curriculum planning project between 2002 and 2005, as
      well as stories of curriculum reform from past deans of the same medical school
      dating back to 1965. Narrative inquiry is used as a means of probing the author's
      own lived experience as coordinator of the new curriculum project and the
      experiences of key members of the NCWG, including the dean, and of former deans
      from the same medical school over its 40-year history. CONCLUSIONS: Through a
      living, telling and retelling of the story of curriculum change, narrative
      inquiry has a role to play in both elucidating the individual lived experience of
      curriculum change and shaping the evolving professional identity of the medical
      educator as an agent of change.

PMID- 19769648
TI  - The effect of differential rater function over time (DRIFT) on objective
      structured clinical examination ratings.
AB  - CONTEXT: Despite the impartiality implied in its title, the objective structured
      clinical examination (OSCE) is vulnerable to systematic biases, particularly
      those affecting raters' performance. In this study our aim was to examine OSCE
      ratings for evidence of differential rater function over time (DRIFT), and to
      explore potential causes of DRIFT. METHODS: We studied ratings for 14 internal
      medicine resident doctors over the course of a single formative OSCE, comprising
      10 12-minute stations, each with a single rater. We evaluated the association
      between time-slot and rating for a station. We also explored a possible
      interaction between time-slot and station difficulty, which would support the
      hypothesis that rater fatigue causes DRIFT, and considered 'warm-up' as an
      alternative explanation for DRIFT by repeating our analysis after excluding the
      first two OSCE stations. RESULTS: Time-slot was positively associated with rating
      on a station (regression coefficient 0.88, 95% confidence interval [CI] 0.38
      1.38; P = 0.001). There was an interaction between time-slot and station
      difficulty: for the more difficult stations the regression coefficient for time
      slot was 1.24 (95% CI 0.55-1.93; P = 0.001) compared with 0.52 (95% CI - 0.08 to
      1.13; P = 0.09) for the less difficult stations. Removing the first two stations
      from our analyses did not correct DRIFT. CONCLUSIONS: Systematic biases, such as
      DRIFT, may compromise internal validity in an OSCE. Further work is needed to
      confirm this finding and to explore whether DRIFT also affects ratings on
      summative OSCEs. If confirmed, the factors contributing to DRIFT, and ways to
      reduce these, should then be explored.

PMID- 19769649
TI  - Multiple mini-interviews versus traditional interviews: stakeholder acceptability
      comparison.
AB  - CONTEXT: The McGill University Faculty of Medicine undertook a pilot, simulation
      based multiple mini-interview (MMI) for medical school applicant selection, which
      ran simultaneously with traditional unstructured interviews (all applicants
      underwent both processes). This paper examines major stakeholder (applicants and
      evaluators) opinions towards the MMI compared with traditional interviews,
      including perceptions about the feasibility and utility of the MMI. METHODS: A
      total of 100 candidates applying to McGill University Medical School were
      enrolled in the pilot comparison of the MMI with the traditional, unstructured
      interview. Applicants' opinions were obtained by questionnaire shortly after the
      process (for all applicants) and approximately 6 months after the interviews (for
      non-accepted applicants). Evaluators' perceptions were also surveyed.
      Questionnaires contained both quantitative items and space for qualitative
      impressions. Descriptive statistics, repeated measures analysis of variance
      (manova) and analysis of the topics raised in written comments were conducted.
      RESULTS: Univariate analyses of response scores revealed statistically
      significant differences, with the MMI rated more highly than the traditional
      interview on fairness, imposition of stress and effectiveness as a measurement
      tool. Compared with the traditional interview, applicants also felt the MMI: (i)
      allowed them to be competitive; (ii) was enjoyable, and (iii) was often a
      favourite part of their interview experience. It should be noted that applicants
      were aware that their MMI score would be included in their overall interview
      rating. Written comments were positive with regard to, for example, fairness, the
      provision of opportunities to show one's strengths, and appreciation of the
      fidelity of the simulations. Evaluators' responses were in agreement with
      applicants' responses, albeit that overall they expressed more caution about the
      MMI. CONCLUSIONS: Results suggest the MMI is a promising selection tool from the
      point of view of both applicants and evaluators. Both groups expressed concerns,
      but overall the response was favourable for the MMI in comparison with
      traditional interviews, and the MMI has been adopted by McGill University's
      medical school.

PMID- 19769650
TI  - Predicting medical students' intentions to take up rural practice after
      graduation.
AB  - OBJECTIVES: Using a novel longitudinal tracking project, this study develops and
      evaluates the performance of a predictive model and index of rural medical
      practice intention based on the characteristics of incoming medical students.
      METHODS: Medical school entry survey data were obtained from the Medical Schools
      Outcome Database (MSOD) project implemented in all Australian and New Zealand
      medical schools and coordinated through Medical Deans Australia and New Zealand,
      the representative body for the Deans of 18 Australian and two New Zealand
      medical schools and faculties. The medical school commencement survey collects
      data on students' education and family background, including rural upbringing,
      personal circumstances and scholarships, and on their practice intentions in
      terms of location and specialty. The MSOD will also allow tracking of medical
      graduates after graduation. Logistic regression modelling was used to develop a
      predictive model of rural practice intention. Split-sample validation was used to
      gain some insight into the stability of performance of the model. RESULTS:
      Response rates to the MSOD survey exceeded 90% on average. The model findings
      confirm and extend previous research examining the association of medical student
      characteristics with intention to take up rural medical practice. The
      statistically significant independent factors in the model included students'
      rural backgrounds, financial arrangements and intentions regarding specialist
      versus generalist practice upon graduation. Model performance was good, with an
      area under the receiver-operator characteristics curve of 0.86, and reproducible,
      with an area in a validation sample of 0.83. CONCLUSIONS: The model and related
      index provide important insights into individual factors associated with rural
      practice intention among students commencing medical studies. The model can also
      provide a means for optimising the use of scarce medical programme resources,
      thereby helping to improve the supply of rural medical practitioners. This study
      illustrates the power and potential of a robust, consistent, systematic
      longitudinal tracking project.

PMID- 19769651
TI  - Problem-based training for medical students reduces common prescription errors: a
      randomised controlled trial.
AB  - CONTEXT: Avoidable drug-related problems (DRPs) cause substantial morbidity,
      mortality and costs. As most prescription errors are committed by recently
      graduated doctors, undergraduate training should specifically address DRPs.
      OBJECTIVES: This study set out to investigate whether a DRP teaching module can
      reduce prescription errors made by advanced medical students in varying clinical
      contexts. METHODS: A total of 74 Year 5 medical students (mean age 25 +/- 3
      years; 24 men, 50 women) participated in a randomised controlled crossover study.
      Students filled in patients' prescription charts before and after a special DRP
      training module and a control intervention. The 1-week training module comprised
      a seminar on common prescription errors, a prescribing exercise with a
      standardised paper case patient, drafting of inoperative prescription charts for
      real patients and discussions with a lecturer. During the observation points,
      prescription charts for standardised patient cases in different clinical contexts
      had to be completed. These prescription charts were subsequently analysed by two
      independent raters using a checklist for common prescription errors. RESULTS:
      Prior to training, students committed a mean of 69 +/- 12% of the potential
      prescription errors. This decreased to 29 +/- 15% after DRP training (P < 0.001).
      CONCLUSIONS: Prescription errors can be significantly reduced in a relatively
      brief training time by implementing a specific DRP teaching module.

PMID- 19769652
TI  - Better doctor efficiency is the real key to better productivity.

PMID- 19769653
TI  - An apple and a knife to teach basic echocardiography.

PMID- 19769654
TI  - Comments on within-station between-sites variation.

PMID- 19769655
TI  - Upcoming evidences on prostate-specific antigen-based screening for men at risk
      of prostate cancer.

PMID- 19769656
TI  - Docetaxel-based chemotherapy with zoledronic acid and prednisone in hormone
      refractory prostate cancer: factors predicting response and survival.
AB  - OBJECTIVES: To evaluate the efficacy of docetaxel/prednisone and zoledronic acid
      in hormone refractory prostate cancer (HRPC) patients and to analyze prognostic
      factors predicting overall survival. METHODS: Forty-four HRPC patients were given
      docetaxel (75 mg/m(2)), prednisone and zoledronic acid (4 mg) every three weeks.
      Overall and progression-free survival curves were calculated. Using the log-rank
      test, variables predicting overall survival (age, Gleason score, baseline
      prostate-specific antigen [PSA], percentage PSA decline, nadir PSA, number of
      chemotherapy cycles) were calculated. RESULTS: Median age was 66 years and mean
      PSA 171.25 ng/mL. The average number of given cycles was 6.3. A good PSA response
      (>50% decline) was observed in 26/44 cases (59.1%). A total of 17/44 (38.6%)
      patients expired with a median overall survival of 62.4 weeks. Patients with a
      Gleason score less than 7, who received more than four cycles and with a more
      than-50% decline in PSA had significantly better survival. Variables like age,
      baseline PSA and nadir PSA did not significantly affect survival. CONCLUSION: The
      combination of docetaxel/zoledronic/prednisone is safe and effective in the
      management of HRPC. Patients with a Gleason score <7, PSA decline >50% and those
      who receive more than four cycles have significantly better survival.

PMID- 19769657
TI  - Editorial Comment to docetaxel-based combination chemotherapy with zoledronic
      acid and prednisone in hormone refractory prostate cancer: Factors predicting
      response and survival.

PMID- 19769658
TI  - A case of oncocytic papillary renal cell carcinoma.
AB  - Papillary renal cell carcinomas (RCC) are the second most frequently identified
      pathological subtypes of RCC. Occasionally, papillary RCC demonstrate
      pathological characteristics of renal oncocytomas (RO), benign renal tumors. We
      report the case of an 81-year-old woman with an oncocytic papillary RCC, which
      was difficult to differentiate from a hybrid of RO and papillary RCC, who
      underwent left radical nephrectomy. Morphological examination showed oncocytic
      tumor region and partially scattered regions with papillary structure.
      Immunohistochemical examinations demonstrated strongly positive staining of alpha
      methylacyl-CoA racemase in the papillary region and negative staining of
      progesterone receptor and CD117 in both regions. Fluorescence in situ
      hybridization confirmed the increased number of copies of chromosome 7 in the
      papillary region. Comprehensively, this case could be diagnosed as oncocytic
      papillary RCC. No evidence of disease recurrence was found at 12 months' follow
      up.

PMID- 19769659
TI  - Leiomyosarcoma of the renal vein.

PMID- 19769660
TI  - Ewing's sarcoma/primitive neuroectodermal tumor of the prostate.

PMID- 19769661
TI  - Metastasis to the penis from cecum carcinoma.

PMID- 19769662
TI  - Successful treatment by transperineal percutaneous sclerosis with minocycline
      hydrochloride for imperforate Cowper's syringocele in a young man.

PMID- 19769664
TI  - Consolidating knowledge.

PMID- 19769665
TI  - A retrospective study of the MRI findings in 18 dogs with stifle injuries.
AB  - OBJECTIVES: To make an objective assessment of the usefulness of magnetic
      resonance imaging in the diagnosis of meniscal damage and cranial cruciate
      ligament disease in the canine stifle by comparing magnetic resonance imaging
      findings with surgical findings. METHODS: Magnetic resonance images of 18 stifles
      from 18 dogs which had undergone magnetic resonance imaging for the investigation
      of stifle disease were reviewed. For every stifle, the menisci and cranial
      cruciate ligaments were assessed according to predetermined criteria. The
      magnetic resonance imaging findings were compared with the reported surgical
      findings and the sensitivity, specificity, positive and negative predictive
      values (PPV and NPV) were calculated using the surgical findings as the gold
      standard. Kappa analysis was used as an objective measure of agreement between
      surgical and magnetic resonance imaging findings. For 11 stifles, meniscal
      evaluation by three different observers was used to measure interobserver
      agreement using Kappa analysis. RESULTS: Magnetic resonance imaging was
      demonstrated to be an accurate technique in the detection of meniscal injury
      (k=0.86), with excellent interobserver agreement (k=0.89 to 1.0). Disruption of
      cranial cruciate ligament continuity and an increase in ligament intensity were
      found to be useful criteria in the diagnosis of cranial cruciate ligament
      rupture. CLINICAL SIGNIFICANCE: Magnetic resonance imaging offers a non-invasive
      alternative to exploratory surgery in the evaluation of cranial cruciate ligament
      and meniscal disease.

PMID- 19769666
TI  - The efficacy of chlorhexidine gluconate in canine skin preparation - practice
      survey and clinical trials.
AB  - OBJECTIVES: To determine the use in practice and efficacy of different
      concentrations of chlorhexidine gluconate for canine pre-operative skin
      preparation. METHODS: Questionnaires were used to establish which antiseptics and
      techniques were used for patients undergoing elective neutering. In a clinical
      study, five different concentrations of chlorhexidine gluconate - 0 per cent (tap
      water, as a control) 1, 2, 3 and 4 per cent - were tested on 50 dogs undergoing
      elective ovariohysterectomies and orchidectomies. RESULTS: A variety of
      preparation practices occurred but only 21 per cent of the veterinary nurses
      surveyed were aware of the concentration and contact time they used whilst
      preparing animals. The clinical study revealed there was a significant difference
      (P<0.001) between the different concentrations used. All concentrations of
      chlorhexidine were significantly more effective than the control tap water. There
      was a tendency towards increasing efficacy as concentration increased from 1 to 4
      per cent but this was not statistically significant. CLINICAL SIGNIFICANCE: The
      lack of significant differences in efficacy between the different concentrations
      of chlorhexidine gluconate means that current practices may be adequate, although
      if the chlorhexidine gluconate concentrations and contact times used are unknown,
      they may be lower than those tested here and, possibly, ineffective, especially
      if contact times are short.

PMID- 19769667
TI  - Aetiology and outcome in 90 cats presenting with dyspnoea in a referral
      population.
AB  - OBJECTIVES: Dyspnoea is an unspecific severe presenting sign, which can be life
      threatening and requires prompt treatment. Dyspnoeic cats often have significant
      underlying disease. Underlying aetiologies in cats that presented with dyspnoea
      were reviewed, and associations with patient signalment and outcome were
      investigated. METHODS: The case records of 90 dyspnoeic cats were retrospectively
      reviewed and separated into different groups depending on aetiology (cardiac,
      respiratory, neoplastic and trauma). Duration of clinical signs, presentation,
      hospitalisation length and survival were analysed. RESULTS: Cardiac (38 per
      cent), respiratory (32 per cent) and neoplastic (20 per cent) diseases were
      common causes of feline dyspnoea. Cats with respiratory causes had longer
      duration of clinical signs (P<0.001) before presentation. Cats with neoplasia
      were significantly older (P<0.001). No significant difference in respiratory
      rates was present between the groups (P = 0.154). High heart rates (P<0.001) and
      abnormalities on cardiac auscultation were more likely in the cardiac group.
      CLINICAL SIGNIFICANCE: Frequent causes of dyspnoea in cats were cardiac disease
      followed by respiratory causes and neoplastic conditions. Heart rate on
      presentation and presence of heart murmurs or gallops are useful to identify
      cardiac causes. Improved proportion surviving was found in the respiratory group
      (P = 0.027), whereas cats with neoplasia had the worst outcome.

PMID- 19769669
TI  - Survey of pet owners' expectations of surgical practice within first opinion
      veterinary clinics in Great Britain.
AB  - OBJECTIVES: The expectations of small animal pet owners in Great Britain were
      evaluated on a number of issues regarding aseptic practice and clinical
      management and compared with final year veterinary students' assessment of actual
      veterinary practice. MATERIALS AND METHODS: A survey was completed by 328 small
      animal pet owners and 56 veterinary practices in Great Britain. Questions from
      the pet owner survey related to expectations and opinions on a number of surgical
      issues and questions from the veterinary surgeon survey examined veterinary
      practice in relation to the same issues. Comparisons were made to determine
      whether there were any differences between pet owner expectations and veterinary
      student assessment of actual practice of small animal first opinion clinics.
      RESULTS: In the majority of issues examined there was a significant mismatch
      between client expectation and provisions made. Of particular importance was the
      discrepancy regarding the use of surgical gloves and administration of analgesia.
      CLINICAL SIGNIFICANCE: These results suggest that attempts should be made to
      understand and improve the disparity that exists between small animal pet owners
      and veterinary surgeons in Great Britain.

PMID- 19769668
TI  - Subcutaneous pre-anaesthetic medication with acepromazine-buprenorphine is
      effective as and less painful than the intramuscular route.
AB  - OBJECTIVES: To compare reaction to injection, sedation and propofol induction
      dose in dogs receiving acepromazine-buprenorphine pre-anaesthetic medication by
      the intramuscular or subcutaneous routes. METHODS: Fifty-two client owned dogs of
      American Society of Anesthesiologists grade I or II anaesthetised for diagnostic
      imaging. Dogs were randomly assigned to receive acepromazine 0.03 mg/kg and
      buprenorphine 0.02 mg/kg either intramuscular or subcutaneous. Reaction to
      injection was scored. Sedation was compared before and one hour after pre
      anaesthetic medication. Propofol was administered in 1 mg/kg incremental
      injections until tracheal intubation was achieved. Total propofol dose was
      recorded. RESULTS: Reaction to injection was significantly greater (P=0.009) in
      the intramuscular group compared to the subcutaneous group. Sedation scores were
      not significantly different (P=0.523) between the intramuscular and the
      subcutaneous group. There was no statistically significant difference in propofol
      dose for induction (P=0.7). CLINICAL SIGNIFICANCE: Acepromazine-buprenorphine pre
      anaesthetic medication provides a similar degree of sedation whether administered
      by the intramuscular or subcutaneous route. The intramuscular route is more
      painful compared to the subcutaneous route.

PMID- 19769670
TI  - Haemangiosarcoma in the uterine remnant of a spayed female dog.
AB  - A 11-year-old, female, spayed greyhound was presented with a haemorrhagic
      discharge from the vulva. Clinical examination, vaginoscopy and a computed
      tomography scan showed an irregular egg-sized mass in the region of the cervix
      and uterine stump. An endoscopic grab biopsy (incisional) suggested a malignant
      mesenchymal tumour. Following this, surgical excision of the cranial vagina,
      cervix and the uterine remnant was performed. The final diagnosis of
      haemangiosarcoma was based on histological examination of the larger excisional
      biopsy specimen and was confirmed by positive immunolabelling of the neoplastic
      endothelial cells for the von Willebrand factor.

PMID- 19769671
TI  - Canine intrapericardial cyst - complicated surgical correction of an unusual
      cause of right heart failure.
AB  - Intrapericardial cysts are non-neoplastic structures that can become clinically
      significant by compressing cardiac chambers. Surgical excision is recommended to
      resolve clinical signs and this has been reported to be easily achieved by blunt
      manipulation. The present report describes a case of an intrapericardial cyst in
      a dog. The singularity of this case lays on the fact that the patient was
      presented unusually late, at the age of four years, and most importantly that its
      surgical correction was significantly complicated by the strong adherence of the
      cyst to both the pericardium and epicardium. This was possibly the result of
      chronic trauma and continued haemorrhage with subsequent healing and fibrosis. It
      is therefore important to consider intrapericardial cysts as a possible
      differential diagnosis in young to middle age patients presented with signs of
      right-sided heart failure. Surgical excision must be planned carefully as this
      may not be as straightforward as previously suggested.

PMID- 19769672
TI  - Survival of a cat with pneumonia due to cowpox virus and feline herpesvirus
      infection.
AB  - Cowpox virus infection in cats is rare and usually leads to cutaneous lesions
      alone. Pulmonary infection and pneumonia have been documented occasionally but
      all such cases described to date have been fatal. Although usually affecting the
      upper respiratory tract, feline herpesvirus can also induce pneumonia. The
      present report describes the case of a cat that recovered from a pneumonia in
      which both poxvirus and feline herpesvirus were demonstrated.

PMID- 19769674
TI  - Ostemyelitis by Pseudomonas aeruginosa in a dog from Rio de Janeiro, Brazil.

PMID- 19769675
TI  - A survey of small animal disease in veterinary practice in the UK.

PMID- 19769676
TI  - Study on canine chronic hepatitis.

PMID- 19769678
TI  - Balancing patient confidentiality and the needs of carers.

PMID- 19769677
TI  - Antigenic and phenotypic variations in fungi.
AB  - Mechanisms to vary the phenotypic characteristics of fungi are diverse and can be
      important for their life cycle. This review summarizes phenotypic variability in
      fungi and divides this phenomenon into three topics: (i) morphological
      transitions, which are environmentally induced and involve the entire fungal
      population, (ii) reversible phenotypic switching between different colony
      morphologies, which is restricted to a small fraction of the population, and
      (iii) antigenic variation of surface antigens, which can be immuno-dominant
      epitopes happens in individual fungal cells.

PMID- 19769679
TI  - Role of cardiac magnetic resonance imaging in ischaemic heart disease.
AB  - Cardiac magnetic resonance imaging is a new imaging method that has much to offer
      clinicians caring for patients with ischaemic heart disease. This article
      describes briefly the basic principles and practical aspects of cardiac magnetic
      resonance imaging, and summarizes the pathophysiology of ischaemic heart disease.
      Then it discusses in detail the use of cardiac magnetic resonance imaging for
      detection of coronary artery disease, and for assessment of acute and stable
      coronary syndromes.

PMID- 19769680
TI  - Preventing healthcare-associated infection: risks, healthcare systems and
      behaviour.
AB  - More than 177 000 potentially preventable healthcare-associated infections (HAIs)
      occur per annum in Australia with sizable attributable mortality. Organizational
      systems to protect against HAI in hospitals in Australia are relatively poorly
      developed. Awareness and practice of infection control by medical and other
      healthcare staff are often poor. These lapses in practice create significant risk
      for patients and staff from HAI. Excessive patient exposure to antimicrobials is
      another key factor in the emergence of antibiotic-resistant bacteria and
      Clostridium difficile infection. Physicians must ensure that their interactions
      with patients are safe from the infection prevention standpoint. The critical
      preventative practice is hand hygiene in accord with the World Health
      Organization 5 moments model. Improving the use of antimicrobials, asepsis and
      immunization also has great importance. Hospitals should measure and feed back
      HAI rates to clinical teams. Physicians as leaders, role models and educators
      play an important part in promoting adherence to safe practices by other staff
      and students. They are also potentially effective system engineers who can embed
      safer practices in all elements of patient care and promote essential structural
      and organizational change. Patients and the public in general are becoming
      increasingly aware of the risk of infection when entering a hospital and expect
      their carers to adhere to safe practice. Poor infection control practice will be
      regarded in a negative light by patients and their families, regardless of any
      other manifest skills of the practitioner.

PMID- 19769681
TI  - Selection of medical patients for prophylaxis of venous thromboembolism based on
      analysis of the benefit-hazard ratio.
AB  - BACKGROUND: Medical patients may benefit from anticoagulant prophylaxis of venous
      thromboembolism (VTE), but assessment of thrombotic risk is complex. I describe a
      method for estimating the minimum thrombotic risk required to ensure that a
      reasonable benefit-hazard ratio is maintained. METHODS: An equation was derived
      relating baseline VTE risk and a minimum acceptable benefit-hazard ratio (R),
      defined as 'pulmonary embolus (PE) alone', 'PE or symptomatic proximal deep
      venous thrombosis (DVT)', or 'PE or any symptomatic DVT' prevented per major
      bleeding. The equation was used to estimate the relative risk (RR) of
      thromboembolism required for net benefit (main outcome measure). The PREVENT
      study was the primary data source, backed by data from two meta-analyses.
      RESULTS: For R ranging from 3 to 10, the RR required for net beneficial
      prophylaxis was 6.5-21.6 (PE alone); 3.0-9.9 (PE or symptomatic proximal DVT);
      and 2.3-7.6 (PE or any symptomatic DVT), respectively. These RR are possible only
      in the presence of risk factors of high weighting. Sensitivity analysis showed
      that the findings were robust to changes in baseline assumptions related to
      thrombosis and bleeding rates. CONCLUSION: A method for risk assessment for
      medical thromboprophylaxis has been developed. The results suggest that only a
      minority of medical patients with high RR should receive prophylaxis.

PMID- 19769682
TI  - Malignant fibrous histiocytoma complicating nephrogenic systemic fibrosis post
      liver transplantation.
AB  - A 46-year-old man with cirrhosis secondary to hepatitis C virus infection and
      alcohol underwent orthotopic liver transplantation, which required urgent re
      grafting because of biliary sepsis from necrosis of the left liver lobe. Recovery
      was complicated by renal failure and nephrogenic systemic fibrosis (probably
      related to intravenous gadolinium exposure). He subsequently developed a
      malignant fibrous histiocytoma. We present this case highlighting the occurrence
      of two rare conditions in the same patient following liver transplantation. We
      believe this is the first case of its kind to be reported.

PMID- 19769683
TI  - A case of uterine tumour resembling ovarian sex cord tumour responding to second
      line, single agent anastrazole.
AB  - Uterine tumour resembling ovarian sex cord tumour (UTROSCT) are a histological
      variant of endometrial stromal sarcomas (ESS). There is no established medical
      management of metastatic UTROSCT or ESS, although there is evidence supporting
      the use of hormonal therapy. Given the success of aromatase inhibitors in breast
      cancer, their potential role in ESS and UTROSCT is of current interest. We report
      the first case of response to second-line, single agent anastrazole in a patient
      with metastatic UTROSCT.

PMID- 19769684
TI  - Fluoroquinolone-induced immune thrombocytopenia: a report and review.
AB  - Fluoroquinolones are an emerging but underrecognized cause of drug-induced
      thrombocytopenia. Due to their broad spectrum they are often used in empirical
      treatment of febrile neutropenic, thrombocytopenic patients following
      myelosuppressive chemotherapy. They are associated with a range of
      immunohaematopathology. A 76-year-old male developed severe thrombocytopenia
      following treatment with ciprofloxacin on two occasions for community-acquired
      pneumonia. The temporal association, response to dechallenge, dramatic response
      to rechallenge and exclusion of other causes combined with detection of platelet
      reactive antibodies of the immunoglobulin G class against glycoprotein IIb/IIIa
      following ciprofloxacin rechallenge makes causality probable. We present a brief
      review of immunohaematopathology associated with fluoroquinolones and draw
      attention to the structural similarity between quinolones and quinine to explore
      potential mechanisms for the phenomenon. Fluoroquinolones can induce drug
      dependent, platelet-reactive antibodies causing complement-mediated destruction
      of platelets. The underlying mechanism to explain this is unclear; however, we
      hypothesize that the chemical similarities shared with quinine may be
      contributory. When using these agents clinicians should be aware of the
      possibility of drug-induced thrombocytopenia or thrombotic thrombocytopenic
      purpura.

PMID- 19769685
TI  - Medicinal use of leeches in the texts of ancient Greek, Roman and early Byzantine
      writers.
AB  - Blood-letting was a common therapeutic method in antiquity; many means were used
      to draw blood, including the application of leeches. In this paper, ancient
      Greek, Roman and Byzantine authors up to the 7th century AD were studied, a
      research that provided us with references that may be divided into two groups:
      those related to the medicinal use of leeches, and those related to cases in
      which leeches were swallowed and had to be removed. In the first group, detailed
      descriptions of the method of usage and of the diseases requiring leeching were
      found. In the second group, brief reference is made to the problems caused by
      swallowing leeches, and to the methods used to expel them from the human
      organism. The earliest references to the medicinal use of leeches may be found in
      the writings of Theocritus (3rd century BC), Nicander (2nd century BC) and Horace
      (1st century BC, while the phenomenon of swallowing a leech is first mentioned in
      one of the Epidaurian 'iamata' dating to the 4th century BC.

PMID- 19769686
TI  - Complications of thoracentesis.

PMID- 19769687
TI  - Pulmonary toxicity associated with infliximab therapy for ulcerative colitis.

PMID- 19769688
TI  - Tako-tsubo cardiomyopathy after observing anaphylaxis.

PMID- 19769689
TI  - Does alcohol play a role in QT prolongation?

PMID- 19769690
TI  - Concordant genetic breaks, identified by combining clustering and tessellation
      methods, in two co-distributed alpine plant species.
AB  - Natural genetic breaks may indicate limitations to gene flow or the presence of
      contact zones of previously isolated populations. Molecular evidence suggests
      that genetic breaks have aggregated in distinct geographical areas. We propose a
      new application of well-established statistical methods for analysing multilocus
      genetic data to identify intraspecific genetic breaks. The methodological
      approach combines Bayesian clustering with a spatially explicit maximum
      difference algorithm to visualize and quantify breaks between clusters. We used
      amplified fragment length polymorphism data of two co-distributed, silicicolous
      alpine plant species, Geum montanum and Geum reptans, exhaustively sampled on a
      consistent, regular grid over their entire range of the European Alps and the
      Carpathians. We found a distinct and highly similar allocation of genetic breaks
      in both species. The pattern of breaks did not conform to scenarios of glacial
      refugial survival, alternatively in peripheral refugia or on nunataks, as
      expected because of the species' ecologies (late-successional low alpine vs.
      early-successional high alpine). Our findings rather substantiated the postulate
      of a general pattern of genetic breaks in alpine plants and corresponded well
      with biogeographical regions formerly described. Our approach could serve as a
      tool not only for landscape genetics and comparative phylogeography, but also for
      floristics or faunistics to compare biogeographic with phylogeographic breaks.

PMID- 19769691
TI  - Genetic variation and local adaptation at a cheatgrass (Bromus tectorum) invasion
      edge in western Nevada.
AB  - Cheatgrass (Bromus tectorum) is an invasive weed in western North America found
      primarily growing at elevations less than 2200 m. We asked whether cheatgrass is
      capable of becoming adapted to a marginal habitat, by investigating a population
      at a high elevation invasion edge. We used a combination of methods, including
      reciprocal field transplants, controlled environment studies and molecular
      analysis. High levels of SSR gene diversity (0.50 vs. 0.43) and comparable
      variation in phenotypic traits were observed at both the invasion edge and a low
      elevation, high-density population. Three heterozygotes were observed in the edge
      population, which is unusual in this predominantly self-pollinating plant. Plants
      from high elevations germinated more slowly in a growth chamber and had slower
      seedling growth rates. Survivorship was low at the edge (13%), compared with the
      low elevation site (55%), but surviving plants were of similar size and had
      equivalent reproductive output. Seed size positively affected survival and plant
      performance in the field and this trait was inherited. Emergence timing affected
      survival at the low elevation site and germination timing was also inherited.
      Local adaptation was seen in the low, rather than in the high elevation site,
      because of differential survival. While there was no evidence for local
      adaptation to the high elevation site observed in the field, family level and
      genotype-level differences in traits that affected field performance, high
      genetic diversity at the invasion edge, and evidence of outcrossing in this
      highly selfing species indicates that the potential for adaptation to a marginal
      habitat exists within this population.

PMID- 19769692
TI  - Female philopatry in coastal basins and male dispersion across the North Atlantic
      in a highly mobile marine species, the sperm whale (Physeter macrocephalus).
AB  - The mechanisms that determine population structure in highly mobile marine
      species are poorly understood, but useful towards understanding the evolution of
      diversity, and essential for effective conservation and management. In this
      study, we compare putative sperm whale populations located in the Gulf of Mexico,
      western North Atlantic, Mediterranean Sea and North Sea using mtDNA control
      region sequence data and 16 polymorphic microsatellite loci. The Gulf of Mexico,
      western North Atlantic and North Sea populations each possessed similar low
      levels of haplotype and nucleotide diversity at the mtDNA locus, while the
      Mediterranean Sea population showed no detectable mtDNA diversity. Mitochondrial
      DNA results showed significant differentiation between all populations, while
      microsatellites showed significant differentiation only for comparisons with the
      Mediterranean Sea, and at a much lower level than seen for mtDNA. Samples from
      either side of the North Atlantic in coastal waters showed no differentiation for
      mtDNA, while North Atlantic samples from just outside the Gulf of Mexico (the
      western North Atlantic sample) were highly differentiated from samples within the
      Gulf at this locus. Our analyses indicate a previously unknown fidelity of
      females to coastal basins either side of the North Atlantic, and suggest the
      movement of males among these populations for breeding.

PMID- 19769693
TI  - Comparison of contemporary mating patterns in continuous and fragmented
      Eucalyptus globulus native forests.
AB  - While habitat fragmentation is a central issue in forest conservation studies in
      the face of broad-scale anthropogenic changes to the environment, its effects on
      contemporary mating patterns remain controversial. This is partly because of the
      inherent variation in mating patterns which may exist within species and the fact
      that few studies have replication at the landscape level. To study the effect of
      forest fragmentation on contemporary mating patterns, including effective pollen
      dispersal, we compared four native populations of the Australian forest tree,
      Eucalyptus globulus. We used six microsatellite markers to genotype 1289 open
      pollinated offspring from paired fragmented and continuous populations on the
      island of Tasmania and in Victoria on mainland Australia. The mating patterns in
      the two continuous populations were similar, despite large differences in
      population density. In contrast, the two fragmented populations were variable and
      idiosyncratic in their mating patterns, particularly in their pollen dispersal
      kernels. The continuous populations showed relatively high outcrossing rates (86
      89%) and low correlated paternity (0.03-0.06) compared with the fragmented
      populations (65-79% and 0.12-0.20 respectively). A greater proportion of trees
      contributed to reproduction in the fragmented (de/d>or= 0.5) compared with the
      continuous populations (de/d = 0.03-0.04). Despite significant inbreeding in the
      offspring of the fragmented populations, there was little evidence of loss of
      genetic diversity. It is argued that enhanced medium- and long-distance dispersal
      in fragmented landscapes may act to partly buffer the remnant populations from
      the negative effects of inbreeding and drift.

PMID- 19769694
TI  - Geographic limits of a clonal population of wheat yellow rust in the
      Mediterranean region.
AB  - Most plant pathogens present complex life cycles, in which the clonal
      reproduction may impede the delimitation of population entities. By studying the
      genetic structure of the wheat yellow rust caused by Puccinia striiformis f.sp.
      tritici (PST), we highlighted difficulties impeding population delimitation in
      highly clonal species. Despite the high dispersal potential of PST, southern
      France isolates were shown to be divergent from a northwestern European
      population. A 2-year survey was performed in the Mediterranean region to assess
      the geographic distribution of southern isolates: 453 isolates collected in 11
      countries were genotyped using 15 simple sequence repeat markers. A subsample was
      analysed for virulence against 23 resistance genes. The dominant strain in the
      western Mediterranean region was further studied with amplified fragment length
      polymorphism markers to test for a geographic substructure. Both 'individual'-
      and 'population'-centred analyses of polymorphism markers revealed two south
      specific groups: a predominant group, with a broad variability and a wide
      distribution in both western and eastern Mediterranean countries, and a minor
      group in the western Mediterranean. The east-west gradient of genetic diversity
      suggested gene flow from the Middle East with subsequent founder effects and
      genetic divergence, and demonstrated the local survival of a western
      Mediterranean population. The high frequency of the resistance gene Yr8 observed
      in cultivars from Tunisia and Algeria may contribute to maintain the north/south
      structure observed in France. In addition to migration and local adaptation, the
      dynamics of clonal lineage diversification and replacement should be considered
      to define population entities in strongly clonal species.

PMID- 19769695
TI  - Blood pressure guidelines--unlocking the evidence remains challenging.

PMID- 19769696
TI  - Type 2 diabetes and HbA1c goal: time for individualised therapy.

PMID- 19769697
TI  - The anion gap revisited.

PMID- 19769698
TI  - Intensive glucose therapy and clinical implications of recent data: a consensus
      statement from the Global Task Force on Glycaemic Control.
AB  - BACKGROUND: There is compelling evidence showing that achieving good glycaemic
      control reduces the risk of microvascular complications in people with type 1 and
      type 2 diabetes. Likewise, there is clear evidence to show that achieving good
      glycaemic control reduces the risk of macrovascular complications in type 1
      diabetes. The UKPDS 10-year follow up suggests that good glycaemic control also
      reduces the risk of macrovascular complications in type 2 diabetes. Despite this,
      recent results from ACCORD, ADVANCE and VADT present conflicting results and data
      from the ACCORD trial appear to suggest that very low HbA(1c) targets (<6.0%)
      may, in fact, be dangerous in certain patient populations. AIM: To review recent
      results from ACCORD, ADVANCE and VADT and provide clear guidance on the clinical
      significance of the new data and their implications for the practising physician
      treating patients with type 2 diabetes. METHODS: A Pubmed search was used to
      identify major randomised clinical trials examining the association between
      glycaemic control and diabetes-associated complications. The data was reviewed
      and discussed by the GTF through a consensus meeting. The recommendations for
      clinical practice in this statement are the conclusions of these analyses and
      discussions. RESULTS: Evidence from ACCORD, ADVANCE, VADT and UKPDS suggests that
      certain patient populations, such as those with moderate diabetes duration and/or
      no pre-existing CVD, may benefit from intensive blood glucose control. These
      trials highlight the benefit of a multifactorial treatment approach to diabetes.
      However, ACCORD results indicate that aggressive HbA(1c) targets (<6.0%) may not
      be beneficial in patients with existing CVD and a longer duration of diabetes.
      CONCLUSIONS: Glycaemic control remains a very important component of treatment
      for type 2 diabetes and contrasting results from the ACCORD, ADVANCE and VADT
      should not discourage physicians from controlling blood glucose levels.

PMID- 19769699
TI  - Understanding heterogeneity in meta-analysis: the role of meta-regression.
AB  - BACKGROUND: Meta-regression has grown in popularity in recent years, paralleling
      the increasing numbers of systematic reviews and meta-analysis published in the
      biomedical literature. However, many clinicians and decision-makers may be
      unfamiliar with the underlying principles and assumptions made within meta
      regression leading to incorrect interpretation of their results. AIMS: This paper
      reviews the appropriate use and interpretation of meta-regression in the medical
      literature, including cautions and caveats to its use. MATERIALS & METHODS: A
      literature search of MEDLINE (OVID) from 1966-February 2009 was conducted to
      identify literature relevant to the topic of heterogeneity and/or meta-regression
      in systematic reviews and meta-analysis. RESULTS: Meta-analysis, a statistical
      method of pooling data from studies included in a systematic review, is often
      compromised by heterogeneity of its results. This could include clinical,
      methodological or statistical heterogeneity. Meta-regression, said to be a
      merging of meta-analytic and linear regression principles, is a more
      sophisticated tool for exploring heterogeneity. It aims to discern whether a
      linear relationship exists between an outcome measure and on or more covariates.
      The associations found in a meta-regression should be considered hypothesis
      generating and not regarded as proof of causality. CONCLUSIONS: The current
      review will enable clinicians and healthcare decision-makers to appropriately
      interpret the results of meta-regression when used within the constructs of a
      systematic review, and be able to extend it to their clinical practice.

PMID- 19769700
TI  - Subjective well-being as a determinant of individuals' responses to symptoms: a
      biopsychosocial perspective.
AB  - BACKGROUND: Although many models have been developed to explain health behaviour,
      differences in individual response to symptoms remain largely unexplained;
      moreover, they tend to underestimate affective (i.e., emotional) processes and
      they neglect the construct of well-being, despite its predominant role in the
      definition of health. AIM: The development of a novel conceptual framework to
      explain and predict variability in individuals' responses to symptoms, through a
      bio-psychosocial perspective, considering also the potential role of subjective
      well-being. MATERIALS & METHODS: The most widely used health behaviour models
      were being reviewed, as well as their limitations. Based on the evidence in the
      literature, major domains that influence response to symptoms are identified and
      analysed. RESULTS: A new conceptual framework that is not limited to explanation
      of common health behaviours such as treatment seeking or problem identification,
      but draws attention to a broad spectrum of individual reactions and experiences
      following the physical experience of a symptom or medical condition. The role of
      subjective well-being and its determinants are considered as a central concept in
      the proposed framework. DISCUSSION: The present conceptual framework provides a
      comprehensive bio-psychosocial perspective on behavioural outcomes related to
      individual response to symptoms. CONCLUSION: The proposed framework opens a new
      window to patient centred care. Research to evaluate the proposed framework may
      improve the quality of clinical care and overall patient satisfaction.

PMID- 19769701
TI  - Lack of laboratory assessment of severe hyponatraemia is associated with
      detrimental clinical outcomes in hospitalised patients.
AB  - OBJECTIVE: Increased mortality with severe hyponatraemia is well known. What is
      less clear is the mortality risk according to the pattern of the developing
      hyponatraemia and whether this may be affected by the intervention of the
      clinician. METHODS: From our laboratory database, we retrospectively collected
      data of a 12-month period of adult patients with severe hyponatraemia (< or = 120
      mmol/l). One hundred and thirteen patients were identified. Normonatraemic
      controls (n = 113) were identified by plasma sodium of 135 mmol/l over the same
      period, and whose nadir during hospitalisation was > or = 130 mmol/l. Results are
      mean +/- SD unless stated otherwise. Duration of hospitalisation and clinical
      outcomes was confirmed from hospital records. RESULTS: The mean nadir plasma
      sodium of the hyponatraemic group was 116.0 +/- 4.4 mmol/l and 134.0 +/- 2.8
      mmol/l in controls. Although the hyponatraemic patients were younger than
      controls (65.8 +/- 18.4 vs. 72.3 +/- 14.9 years; p = 0.004), they had higher
      mortality (24 vs. 7, p = 0.002) and longer hospitalisation than controls: median
      (IQR), 12 (7-22) vs. 7 (3-16.5) days (p < 0.001). A total of 55 patients
      developed severe hyponatraemia following admission. This subgroup comprised a
      higher proportion of surgical patients (23.6% vs. 1.7%, p < 0.001) than those
      with severe hyponatraemia on admission. Furthermore, both mortality (n = 17 vs. n
      = 7; p = 0.02) and duration of hospitalisation, median 19 days (IQR 10-35) vs.
      9.5 (5-15) days (p < 0.001), were greater. Failure to measure plasma and urinary
      osmolalities was associated with increased mortality. CONCLUSIONS: Severe
      hyponatraemia is associated with prolonged admission and increased mortality
      compared with normonatraemic patients. Progressive hyponatraemia following
      admission incurs a higher risk of death. This may represent illness-severity,
      inappropriate management or inadequate investigation.

PMID- 19769702
TI  - Unperceived treatment gaps in acute coronary syndromes.
AB  - BACKGROUND: Despite a strong evidence-base for several therapies recommended in
      the management of acute coronary syndromes (ACS), many patients do not receive
      these therapies. The barriers preventing translation of evidence into practice
      are incompletely understood. The aim of this study was to survey clinicians
      regarding barriers to implementing recommendations of recently published national
      clinical guidelines and to determine the extent to which these impact clinical
      practice. METHODS: A survey of clinicians at hospitals included in Australian
      Collaborative Acute Coronary Syndromes Prospective Audit (ACACIA, n = 3402,
      PML0051) was conducted, measuring self-stated knowledge, beliefs and guideline
      concordant behaviours in relation to their care of ACS patients. Correlations
      between individual respondents' self-estimated rates and clinician's
      institutional rates of guideline-concordant behaviours were performed. RESULTS:
      Most respondents (n = 50/86, 58%) were aware of current guidelines and their
      scope, achieving 7/10 (Interquartile Range (IQR) = 2) median score on knowledge
      questions. Belief in benefits and agreement with guideline-recommended therapy
      was high. However, none of these factors correlated with increased use of
      guideline therapies. Apart from clopidogrel (r(s) = 0.28, p < 0.01) and early
      interventional therapy for high-risk non-ST elevation myocardial infarction (r(s)
      = 0.31, p < 0.01), there were no significant correlations between individual
      clinicians' self-estimated rates of guideline-concordant practice and rates
      recorded in ACACIA data for their respective institution. CONCLUSION: Beliefs
      about practice do not match actual practice. False beliefs regarding levels of
      evidence-based practice may contribute to inadequate implementation of evidence
      based guidelines. Strategies such as continuous real-time audit and feedback of
      information for the delivery of care may help clinicians understand their levels
      of practice better and improve care.

PMID- 19769703
TI  - Left atrial remodelling in hypertrophic cardiomyopathy: relation with exercise
      capacity and biochemical markers of tissue strain and remodelling.
AB  - BACKGROUND: Left atrial remodelling, assessed as left atrial volume (LAV), has
      been proposed as a good marker of left ventricular diastolic dysfunction. The aim
      of this study was to analyse the influence of LAV on exercise performance in
      hypertrophic cardiomyopathy (HCM), and in a subset of subjects, assess the
      relation of LAV and exercise performance to four biomarkers of disease
      pathophysiology: matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of
      matrix metalloproteinase-1 (TIMP-1) (as indices of tissue remodelling), N
      terminal portion of pro B-type natriuretic peptide (NT-pro-BNP) (associated with
      ventricular dysfunction) and C-reactive protein (CRP, an index of inflammation).
      METHODS: We studied 75 consecutive HCM patients (aged 46 +/- 14 years, 56 men)
      where LAV was calculated assuming the ellipsoid model with two orthogonal planes.
      LAV was indexed to body surface area. Exercise capacity was evaluated by
      treadmill exercise test (symptom limited) and assessed with metabolic equivalent
      units (MET). Basal NT-pro-BNP and CRP levels were measured in 70 patients,
      whereas MMP-2 and TIMP-1 in 43 patients. RESULTS: Enlarged LAV was observed in
      those patients with previous atrial fibrillation (p = 0.016). Mean LAV was
      greater in patients with impaired functional New York Heart Association (NYHA)
      class (p < 0.001). LAV correlated with age (Spearman, r: 0.28), higher maximal
      left ventricular wall thickness (r: 0.32) and raised E/A ratio (r: 0.37) (all p <
      0.01). LAV was significantly correlated with NT-pro-BNP values (r: 0.34; p =
      0.04), MMP-2 (r: 0.32; p = 0.034), CRP (r: 0.33; p = 0.005) and correlated
      inversely with MET units (r: -0.39; p < 0.01). In multivariate analysis, MET
      units were only associated with NT-pro-BNP (p = 0.002) and LAV (p = 0.010).
      CONCLUSIONS: Enlarged LAV is associated with impaired functional NYHA class and
      inversely with treadmill exercise capacity. Enlarged LAV is also associated with
      NT-pro-BNP, MMP-2 and CRP, perhaps as markers of disease severity and tissue
      remodelling. Age, LAV and NT-pro-BNP are independent predictors of exercise
      performance.

PMID- 19769704
TI  - Impact of short-term aerobic interval training on maximal exercise in sedentary
      aged subjects.
AB  - BACKGROUND: Ageing is known to be associated with a decrease in peak oxygen
      consumption (VO2peak) and maximal tolerated power (MTP). Regular physical
      exercise is the most appropriate to improve aerobic capacity, but its effect
      still remained discussed in old people. DESIGN: The aim of this study was to
      determine whether a short interval training session would be associated with
      improvements in exercise efficiency in aged subjects in both genders. METHODS: In
      all, 19 women and 16 men (65.4 +/- 4.9 years) performed a cycle incremental
      exercise test before and after a 9-week period of aerobic interval training
      (twice a week, 30 min session where 6 x 4-min at the first ventilatory threshold
      alternated with 1-min at the second ventilatory threshold) with cycle ergometer.
      Minute ventilation (MV), O(2) uptake (VO(2)) and CO(2) output (VCO(2)) were
      measured breath-by-breath and by an open-circuit metabolic cart. RESULTS: Before
      training, maximal values of MV (MMV), VO2peak, heart rate, systolic blood
      pressure, MTP, blood lactate at MTP recovery and the power at the first (pVT(1))
      and second ventilatory thresholds (pVT(2)) were higher in men compared with
      women. Nine weeks of interval training induced a significant increase in MMV,
      VO2peak, MTP, pVT(1) and pVT(2) and decrease in systolic blood pressure in the
      same way in men than in women, without any significant effect on their maximal
      heart rate values. CONCLUSIONS: These findings suggest that the age-related
      declines in aerobic index are attenuated by a short exercise interval training
      sessions in women and men.

PMID- 19769705
TI  - A comparison of budesonide/formoterol maintenance and reliever therapy vs.
      conventional best practice in asthma management.
AB  - OBJECTIVE: To study the effectiveness and safety of budesonide/formoterol
      (Symbicort) Maintenance And Reliever Therapy (Symbicort SMART, AstraZeneca,
      Sodertalje, Sweden), a simplified management approach with one inhaler compared
      with conventional best practice (CBP) with multiple inhalers in patients with
      persistent asthma. DESIGN: Open-label randomised controlled parallel group trial,
      6-month treatment. PARTICIPANTS: A total of 908 patients > or = 12 years of age,
      with persistent asthma receiving treatment with inhaled corticosteroids (ICS),
      either alone or in conjunction with long-acting beta(2)-agonist. MAIN OUTCOME
      MEASURES: Time to first severe asthma exacerbation and number of severe asthma
      exacerbations. RESULTS: No difference between groups was seen in time to first
      severe exacerbation (p = 0.75). Exacerbation rates were low in both groups. A
      total of 12 patients in the Symbicort SMART group experienced a total of 14
      severe asthma exacerbations, and 19 patients in the CBP group experienced a total
      of 25 severe asthma exacerbations (annual rate 0.07 vs. 0.13 p = 0.09). The mean
      daily dose of ICS expressed in BDP equivalent was significantly lower in the
      Symbicort SMART group (including as-needed use) vs. in the CBP group (749 microg
      vs. 1059 microg; p < 0.0001). Mean scores in Asthma Control Questionnaire, 5
      question version improved significantly in the SMART group compared with the CBP
      group (p = 0.0026). Symbicort SMART and CBP were equally well tolerated. The mean
      drug cost/patient/month was significantly lower for the patients in the Symbicort
      SMART group compared with patients receiving CBP (51.3 euros vs. 66.5 euros; p <
      0.0001). CONCLUSIONS: In Belgian patients, a simplified regimen using
      budesonide/formoterol maintenance and reliever therapy was at least as effective
      at improving clinical control compared with CBP with a significantly lower ICS
      dose and significantly lower drug costs.

PMID- 19769706
TI  - Diagnosis and management of hyponatraemia in hospitalised patients.
AB  - Hyponatraemia is a commonly encountered electrolyte abnormality in hospitalised
      patients and is associated with significant morbidity and mortality. The fact
      that most cases of hyponatraemia are the result of water imbalance rather than
      sodium imbalance underscores the role of antidiuretic hormone (ADH) in the
      pathophysiology. Hyponatraemia can be classified according to the measured plasma
      osmolality as isotonic, hypertonic or hypotonic. Hyponatraemia with a normal
      plasma osmolality usually indicates pseudohyponatraemia, while hyponatraemia
      because of a high plasma osmolality is typically caused by hyperglycaemia. After
      excluding isotonic and hypertonic causes, hypotonic hyponatraemia is further
      classified according to the volume status of the patient as hypovolaemic,
      hypervolaemic or euvolaemic. Hypovolaemic hyponatraemia is accompanied by
      extracellular fluid (ECF) volume deficit, while hypervolaemic hyponatraemia
      manifests with ECF volume expansion. The syndrome of inappropriate ADH (SIADH)
      should be suspected in any patient with euvolaemic hyponatraemia with a urine
      osmolality above 100 mOsm/kg and urine sodium concentration above 40 mEq/l. In
      the management of any hyponatraemia regardless of the patient's volume status, it
      is advised to restrict free water and hypotonic fluid intake. Hypertonic saline
      and vasopressin antagonists can be used to correct symptomatic hyponatraemia. The
      rate of correction is dependent upon the duration, degree of hyponatraemia and
      the presence or absence of symptoms. Symptomatic acute hyponatraemia (< 48 h) is
      a medical emergency requiring rapid correction to prevent the worsening of brain
      oedema. In asymptomatic patients with chronic hyponatraemia (> 48 h or unknown
      duration), fluid restriction and close monitoring alone are sufficient, while a
      slow correction by 0.5 mEq/l/h may be attempted in symptomatic patients.
      Excessive rapid correction should be avoided in both acute and chronic
      hyponatraemia, because it can lead to irreversible neurological complications
      including central osmotic demyelination.

PMID- 19769707
TI  - The relationship of mean platelet volume with the risk and prognosis of
      cardiovascular diseases.
AB  - BACKGROUND: Mean platelet volume (MPV) is arousing increasing interest as a new
      independent cardiovascular risk factor. AIM: To provide a comprehensive review on
      the biological significance, the main determinants and the prognostic
      implications of MPV. METHODS: A literature search was performed using key terms,
      such as 'MPV' or 'mean platelet volume', together with 'stroke', 'myocardial
      infarction' and 'diabetes and 'obesity'. RESULTS: Large platelets are likely more
      reactive: elevated MPV values are associated with a shortened bleeding time and
      increased thromboxane B2 plasma levels. Thus, MPV could be considered an
      indicator of platelet function. Platelet size is mainly determined in the bone
      marrow during megakaryocytopoiesis, and subsequently does not substantially
      change. MPV is only partially regulated by thrombopoietin: in fact, growth
      factors and cytokines may also elicit the production of larger and more reactive
      platelets in the bone marrow, in the presence of conditions capable of increasing
      their concentrations, such as obesity, endothelial dysfunction and possibly
      myocardial and cerebral ischaemia. This phenomenon could play an important role
      in vascular diseases. In fact MPV is predictive of stroke, acute myocardial
      infarction (AMI) and restenosis of coronary angioplasty, is increased in the
      presence of obesity, diabetes mellitus, metabolic syndrome, AMI and stroke and
      has been shown to have a prognostic significance in patients with stroke and AMI.
      CONCLUSION: In assessing whole blood count, MPV should not be undervalued, as its
      increase should suggest a careful assessment of cardiovascular risk.

PMID- 19769708
TI  - Clinical utility of anion gap in deciphering acid-base disorders.
AB  - The anion gap (AG) measurement is a very useful tool in the evaluation of
      patients with acid-base disorders. Once metabolic acidosis is identified, AG will
      provide the important first step in the differential diagnosis of disorders that
      either increase the AG and those that leave the AG unchanged. Delta gap is the
      comparison between change (delta) in the AG and the change (delta) in bicarbonate
      (HCO(3)(-)). Delta ratio, defined as delta AG:delta HCO(3)(-) is usually 1:1 in
      patients with an uncomplicated high AG acidosis. A value below 1:1 suggests a
      combined high and normal AG acidosis. A value above 2:1 suggests a combined
      metabolic alkalosis and a high AG acidosis. Urine AG (unmeasured anions
      unmeasured cations) is an indirect estimate of the urine NH(4)(+) excretion. It
      is typically negative in patients with normal AG metabolic acidosis secondary to
      diarrhoea. Utilisation of AG calculations helps clinicians in identifying and
      treating acid-base disorders.

PMID- 19769709
TI  - Otosclerosis 1: the aetiopathogenesis of otosclerosis.
AB  - Otosclerosis is a bone dystrophy localised to the inner ear and the stapes
      footplate. Otosclerosis is a frequent cause of deafness in adults. The patient
      with otosclerosis typically presents with a history of slowly progressive
      conductive or mixed hearing loss that is usually bilateral and often asymmetric,
      usually between the ages of 15 and 45 years. The disease is characterised by
      alternating phases of bone resorption and formation. The majority of studies on
      families with otosclerosis suggest an autosomal dominant mode of inheritance with
      incomplete penetrance.

PMID- 19769710
TI  - The role of tramadol ER in the treatment of chronic pain.
AB  - Despite its high prevalence, chronic pain is suboptimally treated in
      approximately one half of affected patients. Failure to recognise and manage
      comorbid physical and psychosocial impairments may contribute to the perpetuation
      of chronic pain. Knowledge of the potential advantages and disadvantages of
      available analgesic medications will permit informed selection of the appropriate
      medication for the individual chronic pain patient. Ultimate therapeutic goals
      will also influence analgesic medication selection. For the patient with chronic
      pain requiring analgesic treatment for an extended period of time, long-acting
      analgesics are recommended. Theoretically, these agents will provide sustained
      analgesia by minimising the end-of-dose pain that is often seen with short-acting
      medications, with improved patient convenience and a potential for reduced risk
      of adverse events. The extended-release formulation of tramadol (tramadol ER) has
      proven efficacy in chronic pain conditions such as osteoarthritis and low back
      pain, as well as a favourable tolerability profile. In addition, tramadol ER has
      been shown in clinical trials to improve pain-related sleep disturbances and
      physical function in patients with chronic pain from osteoarthritis and low back
      pain.

PMID- 19769711
TI  - Colas and extreme consumers.

PMID- 19769716
TI  - Role of the elastin receptor complex (S-Gal/Cath-A/Neu-1) in skin repair and
      regeneration.
AB  - Impaired elastic fiber assembly constitutes one major problem in skin wound
      healing. Recent data indicate that a ternary complex involving a splicing form of
      beta-galactosidase associated with cathepsin-A and neuraminidase-1 directs the
      transport of tropoelastin to the fibroblast plasma membrane and participates in
      the deposition of the elastin precursor onto a microfibrillar scaffold. In
      addition, this elastin receptor complex is ubiquitously expressed and also acts
      as a true receptor for elastin-derived peptides produced during the initial stage
      of wound repair following elastase-mediated proteolysis action. Among the
      peptides generated, those having a x.G.x.x.P.G. motif upregulate (i) keratinocyte
      migration, (ii) endothelial cell angiogenic phenotype, (iii) fibroblast
      proliferation, and (iv) induction of the expression of matrix metalloproteinases,
      type I collagen, and tropoelastin. All of these properties could accelerate the
      different stages of wound repair. Elastin-derived peptides from a chemical or a
      proteolytic digest of insoluble elastin alone or linked to the collagen scaffold
      significantly improve skin wound healing and dermal regeneration in vivo in
      several animal models. Such a beneficial influence has been recently extended to
      the treatment of burn patients. In this respect, recent investigations have
      focused on the design of elastin-derived peptides or elastin-building blocks, as
      obtained from peptide chemistry or by genetic engineering, to elaborate
      biocompatible elastin peptides, which are considered as ideal biomaterials for
      "catalyzing" skin repair and regeneration following injury.

PMID- 19769717
TI  - Accelerated closure of skin wounds in mice deficient in the homeobox gene Msx2.
AB  - Differences in cellular competence offer an explanation for the differences in
      the healing capacity of tissues of various ages and conditions. The homeobox
      family of genes plays key roles in governing cellular competence. Of these, we
      hypothesize that Msx2 is a strong candidate regulator of competence in skin wound
      healing because it is expressed in the skin during fetal development in the stage
      of scarless healing, affects postnatal digit regeneration, and is reexpressed
      transiently during postnatal skin wound repair. To address whether Msx2 affects
      cellular competence in injury repair, 3 mm full-thickness excisional wounds were
      created on the back of C.Cg-Msx2(tm1Rilm)/Mmcd (Msx2 null) mice and the healing
      pattern was compared with that of the wild type mice. The results show that Msx2
      null mice exhibited faster wound closure with accelerated reepithelialization
      plus earlier appearance of keratin markers for differentiation and an increased
      level of smooth muscle actin and tenascin in the granulation tissue. In vitro,
      keratinocytes of Msx2 null mice exhibit increased cell migration and the
      fibroblasts show stronger collagen gel contraction. Thus, our results suggest
      that Msx2 regulates the cellular competence of keratinocytes and fibroblasts in
      skin injury repair.

PMID- 19769718
TI  - Differences in collagen architecture between keloid, hypertrophic scar,
      normotrophic scar, and normal skin: An objective histopathological analysis.
AB  - Normotrophic, hypertrophic, and keloidal scars are different types of scar
      formation, which all need a different approach in treatment. Therefore, it is
      important to differentiate between these types of scar, not only clinically but
      also histopathologically. Differences were explored for collagen orientation and
      bundle thickness in 25 normal skin, 57 normotrophic scar, 56 hypertrophic scar,
      and 56 keloid biopsies, which were selected on clinical diagnosis. Image analysis
      was performed by fast fourier transformation. The calculated collagen orientation
      index ranged from 0 (random orientation) to 1 (parallel orientation). The bundle
      distance was calculated by the average distance between the centers of the
      collagen bundles. The results showed that compared with all three types of scars,
      the collagen orientation index was significantly lower in normal skin, which
      indicates that scars are organized in a more parallel manner. No differences were
      found between the different scars. Secondly, compared with normal skin,
      normotrophic scar, and hypertrophic scar, the bundle distance was significantly
      larger in keloidal scar, which suggests that thicker collagen bundles are present
      in keloidal scar. This first extensive histological study showed objective
      differences between normal skin, normotrophic, hypertrophic, and keloidal scar.

PMID- 19769719
TI  - Preliminary development of a diabetic foot ulcer database from a wound electronic
      medical record: a tool to decrease limb amputations.
AB  - Our objective was to create a practical standardized database of clinically
      relevant variables in the care of patients with diabetes and foot ulcers.
      Numerical clinical variables such as age, baseline laboratory values, and wound
      area were extracted from the wound electronic medical record (WEMR). A coding
      system was developed to translate narrative data, culture, and pathology reports
      into discrete, quantifiable variables. Using data extracted from the WEMR, a
      diabetic foot ulcer-specific database incorporated the following tables: (1)
      demographics, medical history, and baseline laboratory values; (2) vascular
      testing data; (3) radiology data; (4) wound characteristics; and (5) wound
      debridement data including pathology, culture results, and amputation data. The
      database contains variables that can be easily exported for analysis. Amputation
      was studied in 146 patients who had at least two visits (e.g., two entries in the
      database). Analysis revealed that 19 (13%) patients underwent 32 amputations
      (nine major and 23 minor) in 23 limbs. There was a decreased risk of amputation,
      0.87 (0.78, 1.00), using a proportional hazards model, associated with an
      increased number of visits and entries in the WEMR. Further analysis revealed no
      significant difference in age, gender, HbA1c%, cholesterol, white blood cell
      count, or prealbumin at baseline, whereas hemoglobin and albumin were
      significantly lower in the amputee group (p<0.05) than the nonamputee group.
      Fifty-nine percent of amputees had histological osteomyelitis based on operating
      room biopsy vs. 45% of nonamputees. In conclusion, tracking patients with a WEMR
      is a tool that could potentially increase patient safety and quality of care,
      allowing clinicians to more easily identify a nonhealing wound and intervene.
      This report describes a method of capturing data relevant to clinical care of a
      patient with a diabetic foot ulcer, and may enable clinicians to adapt such a
      system to their own patient population.

PMID- 19769720
TI  - Guideline concordant venous ulcer care predicts healing in a tertiary care
      Veterans Affairs Medical Center.
AB  - This study describes the impact of 80% adherence to guideline concordant care for
      compression therapy, moist wound-healing environment, and debridement on venous
      ulcer outcomes. The retrospective cohort design included patients from a tertiary
      care Veterans Affairs Medical Center from October 2003 to September 2007. During
      this 5-year interval, 155 patients with 400 venous ulcers met study inclusion. A
      majority of ulcers (n=362) healed, with an average time to healing of 18.1 weeks
      (range 2-209 weeks, median 10.4 weeks). From the multivariate Poisson regression,
      the likelihood of ulcer healing increased when compression therapy was provided
      during at least 80% of visits (relative risk [RR], 1.93; 95% confidence interval
      [CI], 1.27-2.92) or when a moist wound-healing environment was provided during at
      least 80% of visits (RR, 1.63; 95% CI, 1.09-2.42). Debridement alone was not
      significantly associated with ulcer healing (RR, 1.0; 95% CI, 0.61-1.64).
      Patients who received all three treatments during at least 80% of their visits
      were more likely to heal than those who received < 80% treatment (RR, 2.52; 95%
      CI, 1.53-4.16). Guideline concordant venous ulcer care was significantly
      associated with venous ulcer healing, when provided at 80% or more of patient
      visits.

PMID- 19769721
TI  - A multicenter clinical trial of recombinant human GM-CSF hydrogel for the
      treatment of deep second-degree burns.
AB  - Wound healing is a complex and dynamic biological process. The efficacy and
      safety of a recombinant human granulocyte-macrophage colony-stimulating factor
      (rhGM-CSF) hydrogel to promote deep-second-degree burn wound healing is evaluated
      in this study. In this multicenter, randomized, double-blind, and placebo
      controlled clinical trial, 90 patients with deep second-degree burns were
      randomly assigned into two groups. Complete healing time and percentage of wound
      healing at different time points were observed and side effects were recorded. A
      statistically significant difference was noted at each time point (p<0.01). No
      side effects were observed. These results suggest that rhGM-CSF hydrogel can
      significantly accelerate deep second-degree burn wound healing and is considered
      to be safe.

PMID- 19769722
TI  - Homeostasis of the epidermal barrier layer: a theory of how occlusion reduces
      hypertrophic scarring.
AB  - The mechanism of hypertrophic scar reduction using silicone gel sheeting remains
      elusive. We hypothesize that the decrease in scar formation is due to occlusion
      and homeostasis of the barrier layer. Using an established model of hypertrophic
      scarring, rabbits were divided into four groups and scars were tape-stripped or
      occluded with Kelocote, Cavilon, or Indermil, with each rabbit serving as its own
      internal control. All wounds were harvested on day 28 and examined histologically
      to measure the scar elevation index (SEI), epithelial thickness, and cellularity.
      Immunohistochemistry fluorescence was used to quantify inflammation in the
      dermis. Transepidermal water loss (TEWL) was measured for each occlusive agent
      and tape stripping. Ultrastructural analysis was performed by electron
      microscopy. Kelocote, Cavilon, and Indermil all significantly decreased SEI when
      compared with controls. Each of the occlusive treatments was shown to decrease
      TEWL while tape stripping increased TEWL. Tape stripping significantly increased
      the SEI, epithelial thickness, and cellularity. Immunostaining for macrophages
      showed increased density of inflammatory cells in the tape-stripped scars. Under
      electron microscopy, the tape-stripped wounds displayed extensive inflammation
      and keratinocyte damage. Both unwounded skin and occlusion-treated scars did not
      display these characteristics. In conclusion, hypertrophic scarring was reduced
      regardless of occlusive method used. Furthermore, repeated disruption of the
      permeability barrier by tape stripping led to an increase in scarring.
      Ultrastructural analysis suggests that occluded wounds may be in an advanced
      state of wound repair. Occlusion may mediate its effects through establishing
      homeostasis of the epidermal barrier layer.

PMID- 19769723
TI  - Differential expression of matrix metalloproteinases and tissue inhibitors of
      metalloproteinases in anterior cruciate ligament and medial collateral ligament
      fibroblasts after a mechanical injury: involvement of the p65 subunit of NF
      kappaB.
AB  - The anterior cruciate ligament (ACL) is known to have a poor healing ability,
      especially in comparison with the medial collateral ligament, which can heal
      relatively well. In this study, we detected significant increases in the mRNA
      levels of multiple matrix metalloproteinases (MMPs) (MMP-1, -2, -7, -9, -11, -14,
      -17, -21, -23A, -24, -25, -27, and -28) and tissue inhibitors of
      metalloproteinases (TIMPs) (TIMP-1, -2, -3, and -4) in ACL fibroblasts after an
      in vitro injury with an equi-biaxial stretch chamber. However, only some MMPs
      (MMP-7, -9, -14, -21, and -24) showed increases in injured medial collateral
      ligament fibroblasts, and to a much lesser degree than that observed in the
      injured ACL fibroblasts. Zymography revealed a 6.3-fold increase of MMP-2
      activity in injured ACL but not medial collateral ligament fibroblasts, which
      agrees with the global MMP activities assay. Bay-11 and curcumin can
      significantly decrease MMP-2 activities to 13% and 29% in injured ACL
      fibroblasts, respectively, which implies the involvement of p65 subunits of
      nuclear factor kappaB and AP-1 pathways. Furthermore, Bay-11 can decrease the
      global MMP activity released from injured ACL fibroblasts in a dose-dependent
      manner. In summary, the differential expression and activities of MMPs might help
      to explain the poor healing ability of ACL, and the p65 subunit of nuclear factor
      kappaB might be a potential target to facilitate the ACL repair.

PMID- 19769724
TI  - Wound healing in oral mucosa results in reduced scar formation as compared with
      skin: evidence from the red Duroc pig model and humans.
AB  - Scar formation is a common, unwanted result of wound healing in skin, but the
      mechanisms that regulate it are still largely unknown. Interestingly, wound
      healing in the oral mucosa proceeds faster than in skin and clinical observations
      have suggested that mucosal wounds rarely scar. To test this concept, we created
      identical experimental wounds in the oral mucosa and skin in red Duroc pigs and
      compared wound healing and scar development over time. We also compared the pig
      oral mucosal wound healing to similar experimental wounds created in human
      subjects. The findings showed significantly reduced scar formation at both
      clinical and histological level in the pig oral mucosa as compared with skin 49
      days after wounding. Additionally, the skin scars contained a significantly
      increased number of type I procollagen immunopositive cells and an increased
      fibronectin content, while the oral mucosal wounds demonstrated a prolonged
      accumulation of tenascin-C. Furthermore, the pig oral mucosal wounds showed
      similar molecular composition and clinical and histological scar scores to human
      oral mucosal wounds. Thus, the reduced scar formation in the pig oral mucosa
      provides a model to study the biological processes that regulate scarless wound
      healing to find novel approaches to prevent scar formation in skin.

PMID- 19769725
TI  - HaCaT keratinocytes in co-culture with Staphylococcus aureus can be protected
      from bacterial damage by polihexanide.
AB  - Wound healing is compromised by critical colonization and infection with
      bacteria. Hence, antimicrobial agents are used clinically to decrease the
      bacterial load and promote wound healing. Polihexanide (PHMB) has been found to
      be effective against a broad spectrum of micro-organisms and is increasingly
      utilized in rinsing solutions or in combination with wound dressings because of
      its good biocompatibility. In the present study, a co-culture of human
      keratinocytes and Staphylococcus aureus was established to serve as an in vitro
      model for infected wounds. Incubation of keratinocytes with increasing
      concentrations of S. aureus led to a dose-dependent decline of cell viability and
      proliferation. Lactate dehydrogenase release and interleukin-8 liberation were
      found to be elevated under these conditions. Polihexanide dose-dependently was
      able to protect keratinocytes from bacterial damage and re-establish normal human
      cell proliferation in vitro. Furthermore, a dressing consisting of biocellulose
      derived from Acetobacter xylinum with the addition of polihexanide was adept to
      safeguard keratinocytes against S. aureus. In conclusion, the co-culture system
      presented embodies a valuable tool as a model system for infected cells in a non
      healing wound. Furthermore, the results obtained support the favorable function
      of polihexanide in the treatment of infected chronic wounds.

PMID- 19769726
TI  - 3-Deoxyglucosone-collagen alters human dermal fibroblast migration and adhesion:
      implications for impaired wound healing in patients with diabetes.
AB  - The interaction of fibroblasts with the extracellular matrix is critical for
      wound healing. Advanced glycation end products (AGEs) occur through nonenzymatic
      glycation of long-lived proteins such as collagens. One precursor to these
      modifications, 3-deoxyglucosone (3DG), is elevated in patients with diabetes and
      contributes to the accumulation of AGEs on collagen with increasing chronological
      age. Because wound repair is dependent on fibroblast migration, proliferation,
      and expression of extracellular matrix proteins, we examined the role of 3DG
      treated collagen and the subsequent response of fibroblasts to this modification.
      We found that fibroblasts adhere more strongly to 3DG-treated collagen and do not
      migrate efficiently into the wound site. We further show that 3DG-treated
      collagen induces perinuclear localization of focal adhesion kinase and paxillin,
      indicative of decreased association of these proteins with the cytoskeleton.
      Additionally, these cells expressed higher levels of the misfolded indicator
      protein growth arrest and DNA damage inducible gene 153. These data suggest that
      fibroblast/matrix interactions are altered as AGEs accumulate and affect focal
      adhesion formation. Furthermore, 3DG may be a factor mediating chronic wounds
      observed in patients with diabetes and in the elderly by altering the signaling
      within the fibroblast and inducing the misfolding of proteins.

PMID- 19769728
TI  - Androstenediol reverses steroid-inhibited wound healing.
AB  - It is well recognized that stress of any nature will cause a delay in the wound
      healing response. This delayed healing response appears closely associated with
      immune regulators. In this study, CD-1 mice were injected with a long acting form
      of methyl prednisolone to cause a steroid-induced immune suppression. After 24
      hours, two 6-mm full thickness wounds were placed on the animals' backs and one
      group of animals received the immune-regulating hormone, androstenediol. Wound
      contraction was quantified by planimetry for the subsequent 14 days. Animals that
      were stressed with methyl prednisolone but receiving androstenediol contracted
      their open wounds at faster rates compared with methyl prednisolone-stressed
      animals treated with the vehicle alone. These findings suggest that restoration
      of immune regulation by androstenediol can reverse the delayed open wound
      contraction secondary to steroid stress.

PMID- 19769727
TI  - Differential expression of cyclooxygenases in hypertrophic scar and keloid
      tissues.
AB  - Hypertrophic scar (HS) and keloid (KL) are two forms of an abnormal cutaneous
      scarring process, mainly characterized by excessive extracellular matrix
      deposition and fibroblast proliferation. Despite the increased understanding of
      the molecular and cellular events leading to HS and KL, the pathogenesis of these
      lesions remains poorly understood. A pivotal role in the formation of abnormal
      scars has been ascribed to transforming growth factor-beta, whose activity
      appears to be mediated through a link with pathways acting via cyclooxygenases
      (COX-1 and COX-2). To date, there is no report on the in vivo expression of COX-1
      and COX-2 in human HS and KL tissues. Therefore, using immunohistochemistry and
      Western blot analysis, we investigated 36 cases of KL, 32 cases of HS, and 25
      cases of normal skin in order to define the localization and distribution of COX
      1 and COX-2 in the tissues of these scar lesions and the overlying epidermis. The
      results mainly show the following: (a) a significant overexpression of COX-1 in
      HS tissues and the overlying epidermis as compared with normal skin and KL
      tissues and (b) a significant overexpression of COX-2 in KL tissue and the
      overlying epidermis in contrast to normal skin and HS tissues. Our data support
      the hypothesis that both COXs are involved in the pathogenesis of scar lesions in
      different ways and, particularly, COX-1 in the formation of HS and COX-2 in the
      formation of KL. In addition, the overexpression of COX-1 and COX-2 in the
      epidermis overlying HS and KL tissues, respectively, underlines the importance of
      epithelial-mesenchymal interactions in the pathogenesis of scar lesions.

PMID- 19769730
TI  - Some scientific and organizational challenges in cancer immunology.
AB  - This volume provides a small sampling of the rapidly growing science of cancer
      immunology. Growth in the field includes advances on the requirements for
      immunization or vaccination and the ways in which immunity can be suppressed or
      blocked, including active tumor-based mechanisms. I would like to introduce the
      papers in this volume and then deal with a subject that pervaded many discussions
      among symposium participants. The subject is the need for a much better supported
      and organized effort to design optimal studies of immunology in cancer patients
      so that cancer vaccines can become a major means to prevent and treat this
      disease.

PMID- 19769731
TI  - The human cancer antigen mesothelin is more efficiently presented to the mouse
      immune system when targeted to the DEC-205/CD205 receptor on dendritic cells.
AB  - To develop a tumor vaccine directly targeting tumor antigen to dendritic cells in
      situ, we engineered human mesothelin (MSLN) into an antibody specific for mouse
      DEC-205, a receptor for antigen presentation. We then characterized both T cell
      and humoral responses to human MSLN and compared immunizing efficacy of DEC-205
      targeted MSLN to nontargeted protein after a single-dose immunization. Targeting
      human MSLN to DEC-205 receptor induced stronger CD4(+) T-cell responses compared
      to high doses of mesothelin protein. Approximately 0.5% CD4(+) T cells were
      primed to produce IFN-gamma, tumor necrosis factor-alpha, and IL-2 via
      intracellular cytokine staining, and the T cells also could proliferate rapidly.
      The immune response exhibited breadth because the primed CD4(+) T cells responded
      to at least three epitopes in the H-2(b) background. Targeting MSLN protein to
      DEC-205 receptor also resulted in cross-presentation to CD8(+) T cells. Antibody
      responses against human MSLN were also detected in serum from primed mice by
      ELISA assays. In summary, targeting of MSLN to DEC-205 improves the induction of
      CD4(+) and CD8(+) T-cell immunity accompanied by an antibody response. DEC-205
      targeting could be valuable for enhancing immunity to MSLN in cancers where this
      nonmutated protein is expressed.

PMID- 19769732
TI  - Brain tumor immunotherapy with type-1 polarizing strategies.
AB  - Although the safety of vaccine approaches for central nervous system (CNS)
      malignancies has been established in early phase clinical trials, the success of
      a vaccine strategy will depend critically on the ability of effector T cells to
      home in to CNS tumors and durably exert antitumor effects. Based on our recent
      studies, efficient CNS tumor homing is a characteristic of cytotoxic T
      lymphocytes (CTLs) with a type 1 phenotype (Tc1), and this appears to be related
      to the Tc1 response to the type 1 CXC chemokine ligand (CXCL) 10 [also known as
      interferon (IFN)-inducible protein (IP)-10] and expression of an integrin
      receptor very late antigen (VLA)-4 on Tc1. In addition, we have previously shown
      that direct intratumoral delivery of dendritic cells (DCs) ex vivo engineered to
      secrete IFN-alpha further enhances Tc1 homing via upregulation of CXCL10/IP-10 in
      the tumor microenvironment. As a means to induce IFN-alpha and CXCL10/IP-10 in
      the CNS tumor microenvironment in a clinically feasible manner, we used
      administration of polyinosinic-polycytidylic acid stabilized by lysine and
      carboxymethylcellulose (poly-ICLC), a ligand for toll-like receptor 3 and
      melanoma differentiation-associated gene 5 (MDA5) in combination with
      vaccinations targeting CTL epitopes derived from glioma-associated antigens
      (GAAs). The combination of subcutaneous vaccination and i.m. poly-ICLC
      administration remarkably promoted systemic induction of antigen GAA-specific
      Tc1s expressing VLA-4 in the CNS tumors and improved the survival of tumor
      bearing mice in the absence of detectable autoimmunity. Based on these data, we
      have implemented a phase I/II vaccination study using type 1 polarizing DCs
      loaded with GAA peptides in combination with poly-ICLC in patients with recurrent
      malignant glioma.

PMID- 19769734
TI  - Dendritic cell-based vaccines for pancreatic cancer and melanoma.
AB  - Based on leads from our recent animal studies, we are embarking on a series of
      new clinical trials to evaluate potential improvements in dendritic cell (DC)
      based vaccines for melanoma and pancreatic cancer. The first new strategy
      involves the use of a powerful chemokine (denoted secondary lymphoid tissue
      chemokine; SLC/CCL-21), which can both create functioning lymph node-like
      structures at sites of vaccination with tumor-loaded DCs and dramatically enhance
      vaccine efficacy in animal tumor models. Using this strategy, we are embarking on
      a clinical trial in melanoma patients with the intent to create functioning,
      ectopic, lymph node-like structures to enhance host antitumor immunity. The
      second strategy, in the setting of pancreatic cancer, involves a gene therapy and
      immunotherapy combination of a locally administered tumor necrosis factor-alpha
      gene vector followed by radiation (to induce tumor apoptosis/necrosis) and
      intratumorally administered monocyte-derived DCs (to uptake and present antigens
      from dying tumor cells to elicit potent, systemic, antitumor immunity).

PMID- 19769733
TI  - Harnessing human dendritic cell subsets to design novel vaccines.
AB  - Dendritic cells (DCs) orchestrate a repertoire of immune responses that endow
      resistance to infection and tolerance to self. DC plasticity and subsets are
      prominent determinants of the quality of elicited immune responses. Different DC
      subsets display different receptors and surface molecules and express different
      sets of cytokines/chemokines, all of which lead to distinct immunological
      outcomes. Recent findings on human DC subsets and their functional specialization
      have provided insights for the design of novel human vaccines.

PMID- 19769735
TI  - Combining conventional therapies with intratumoral injection of autologous
      dendritic cells and activated T cells to treat patients with advanced cancers.
AB  - Dendritic cells (DCs) are potent antigen-presenting cells that have been used in
      cancer immunotherapy. To take advantage of the ability of DCs to acquire
      antigenic materials from their environment and generate primary as well as recall
      immune responses, 37 patients with advanced cancers were enrolled in a series of
      protocols based on direct intratumoral injection of immature DCs. To augment
      antigen uptake and antitumor immune response, DC injection was combined with
      radiotherapy or chemotherapy and/or injection of activated T cells. Treatments
      were well tolerated with no adverse reactions. Clinical responses were based on
      Response Evaluation Criteria in Solid Tumors, with the majority of patients
      showing stable disease. One of two patients who also received local radiation
      achieved a sustained complete response at injected and metastatic sites. The
      clinical responses observed in cancer patients with advanced disease suggest
      potential effectiveness of combination strategies and establish the basis for the
      current treatment protocol that is underway.

PMID- 19769736
TI  - Witch hunt against tumor cells enhanced by dendritic cells.
AB  - Conventional cancer treatments mediate their effects via the direct elimination
      of tumor cells. Nonetheless, recent evidence indicates that radiotherapy and some
      chemotherapeutic agents can also induce specific immune responses that contribute
      to therapeutic outcomes. Two major tumor-intrinsic changes that determine the
      immune response against tumors have been identified: the translocation of
      calreticulin to the plasma membrane and the release of high-mobility group box 1
      protein. Together, these changes improve engulfment and processing of apoptotic
      bodies by dendritic cells, which are involved in the cross-priming of antitumor T
      lymphocytes in vivo. We review these two molecular mechanisms that dictate the
      radio/chemotherapy-elicited antitumor immune response and discuss how this
      knowledge can be clinically exploited to predict and also ameliorate the success
      of chemo/radiotherapy.

PMID- 19769737
TI  - Harnessing CD1d-restricted T cells toward antitumor immunity in humans.
AB  - Natural killer T (NKT) cells are a distinct subset of T cells that recognize
      lipid antigens in the context of CD1d molecules. There is a considerable body of
      evidence implicating a role for NKT cells in regulating antitumor immunity in
      mice. alpha-Galactosylceramide (alpha-GalCer) is a potent agonist ligand for type
      I NKT cells. We and others have shown that injection of alpha-GalCer-loaded
      dendritic cells leads to clear expansion of NKT cells in vivo in cancer patients.
      Preclinical studies suggest the capacity of thalidomide analogues to enhance
      ligand-dependent NKT activation and provide the rationale for combination
      approaches that are now being designed. Recently, we demonstrated the presence of
      CD1d-restricted T cells specific for an inflammation-associated lipid,
      lysophosphatidylcholine, in patients with advanced myeloma. These studies suggest
      that type II NKT cells may play a role in sensing and regulating inflammation.
      Harnessing CD1d-restricted T cells in cancer may depend on regulating the balance
      between type I and II NKT cells and holds promise as a broad strategy for immune
      therapy of several cancers.

PMID- 19769738
TI  - Immunity against cyclin B1 tumor antigen delays development of spontaneous cyclin
      B1-positive tumors in p53 (-/-) mice.
AB  - We previously identified cyclin B1-specific T cells and antibodies in cancer
      patients with cyclin B1-positive (+) tumors and also in some healthy individuals.
      We also demonstrated that these responses may be important in cancer
      immunosurveillance by showing that vaccination against cyclin B1 prevents growth
      of transplantable cyclin B1(+) tumors in mice. Constitutive overexpression of
      cyclin B1 was determined to correlate with the lack of p53 function. This allowed
      us to use p53(-/-) mice as a model that better approximates human disease. These
      p53(-/-) mice spontaneously develop cyclin B1(+) tumors. At 5-6 weeks of age,
      when the mice were still healthy with no evidence of tumor, they received the
      cyclin B1 vaccine and were then observed for tumor growth. We demonstrate that
      cyclin B1 vaccination delays spontaneous cyclin B1(+) tumor growth and increases
      median survival of tumor-bearing p53(-/-) mice.

PMID- 19769739
TI  - Targets of protective tumor immunity.
AB  - The identification of antigens associated with tumor destruction is a major goal
      of cancer immunology. Several genetic and biochemical techniques have revealed a
      broad range of gene products that elicit immune recognition in cancer patients,
      but the biologic importance of these responses in most cases is poorly
      understood. While some targets are linked to tumor regressions in the context of
      adoptive cellular therapies or cancer vaccinations, the possible roles of
      immunity to most antigens in disease pathogenesis and clinical outcomes remain to
      be elucidated. One strategy for characterizing antigens that elicit clinically
      significant immune recognition involves the study of patients who achieve durable
      clinical benefits from immune treatments. Through this approach, we uncovered the
      immunogenicity of major histocompatibility chain-related protein A (MICA), which
      is a ligand for NKG2D, and ERp5, a protein disulfide isomerase involved in MICA
      shedding. Our findings suggest that components of the NKG2D pathway may be
      attractive targets for therapeutic monoclonal antibodies.

PMID- 19769740
TI  - Identification of immunologic biomarkers associated with clinical response after
      immune-based therapy for cancer.
AB  - The identification of immunologic biomarkers associated with clinical response
      after immune intervention for cancer is an area of intensive investigation. The
      field would benefit from a more systemic and directed approach for biomarker
      identification and evaluation. Lessons can be learned from other fields, such as
      cancer diagnostics, as to how to develop response-associated biomarkers. Studies
      in both human in vitro models as well as murine models of cancer can
      significantly inform and streamline the choice of candidates. Adoptive T-cell
      therapy is an interesting model for exploring potential immunologic surrogates
      that may predict clinical response. Most likely the clinical effectiveness of
      immune-based treatments will be predicted by panels of markers rather than single
      assays of a specific immune effector cell.

PMID- 19769742
TI  - Clinical use of anti-CD25 antibody daclizumab to enhance immune responses to
      tumor antigen vaccination by targeting regulatory T cells.
AB  - CD4(+) regulatory T cells frustrate productive tumor immune surveillance and
      represent an obstacle for cancer immunotherapy. In mice, anti-CD25 antibody is an
      effective method of depleting CD25(+) FOXP3(+) T regulatory cells (Tregs) in vivo
      and enhancing cancer immunity. Here, we propose the use of the anti-CD25
      monoclonal antibody daclizumab for the depletion of Tregs in cancer patients. In
      early results from an ongoing clinical trial, a single intravenous infusion of
      daclizumab in patients with metastatic breast cancer is associated with a marked
      and prolonged elimination of CD25(+) FOXP3(+) Tregs in peripheral blood. When a
      cancer antigen peptide vaccine is administered during the daclizumab-induced Treg
      nadir, effective generation of cytotoxic T lymphocytes has been observed,
      including those specific for neo-antigens, such as cytomegalovirus peptide used
      as an immunological control. If confirmed in additional patients, these
      observations suggest that daclizumab may be an effective and available
      therapeutic agent for Treg modulation in patients with cancer.

PMID- 19769743
TI  - Strategies to enhance the therapeutic activity of cancer vaccines: using melanoma
      as a model.
AB  - Although there has been initial success with some types of immunotherapy, such as
      adoptive cellular therapy and monoclonal antibody therapy for cancer, the
      experience with therapeutic cancer vaccines has been much less encouraging.
      Almost all randomized phase III trials testing therapeutic cancer vaccines have
      failed to meet their end points. There are several potential explanations for
      this, ranging from factors related to the clinical trial design and the vaccine
      itself. Perhaps the most important are host-related factors. Specifically,
      progression and metastases of many cancers are associated with induction of
      multiple cancer-specific immune-inhibitory pathways. These inhibitory pathways
      include induction of T-cell anergy through dendritic cell dysfunction, release of
      immunosuppressive cytokines, T-cell exhaustion through inhibitory T-cell
      signaling and T regulatory cell-mediated tumor-specific immune suppression. All
      of these pathways have been shown to be operational in patients with melanoma. To
      enhance the activity of therapeutic cancer vaccines, these immunosupressive
      pathways need to be addressed and reversed. A number of new immunomodulatory
      reagents that are able to interfere with some of these pathways are now being
      assessed in the clinic. Sanofi Pasteur designed a clinical trial in patients with
      advanced or metastatic melanoma that is intended to both induce tumor-specific T
      cell responses and modulate or reverse some of the immune suppression pathways
      that the melanoma has induced. To accomplish this, the recently optimized ALVAC
      melanoma multi-antigen vaccine is administered with high doses of IFN-alpha.
      Clinical trial parameters have also been optimized to enhance the likelihood of
      inducing and documenting antitumor activity. Success with other therapeutic
      cancer vaccine approaches will likely require similar approaches in which
      promising immunogenic vaccines are integrated with biologically and clinically
      active immunomodulatory reagents.

PMID- 19769741
TI  - Harnessing dendritic cells to generate cancer vaccines.
AB  - Passive immunotherapy of cancer (i.e., transfer of T cells or antibodies) can
      lead to some objective clinical responses, thus demonstrating that the immune
      system can reject tumors. However, passive immunotherapy is not expected to yield
      memory T cells that might control tumor outgrowth. Active immunotherapy with
      dendritic cell (DC) vaccines has the potential to induce tumor-specific effector
      and memory T cells. Clinical trials testing first-generation DC vaccines pulsed
      with tumor antigens provided a proof-of-principle that therapeutic immunity can
      be elicited. Newer generation DC vaccines are built on the increased knowledge of
      the DC system, including the existence of distinct DC subsets and their
      plasticity all leading to the generation of distinct types of immunity. Rather
      than the quantity of IFN-gamma-secreting CD8(+) T cells, we should aim at
      generating high-quality, high-avidity, polyfunctional effector CD8(+) T cells
      able to reject tumors and long-lived memory CD8(+) T cells able to prevent
      relapse.

PMID- 19769744
TI  - Hematopoietic stem and progenitor cells and the inflammatory response.
AB  - Cells of the vertebrate immune system are continuously regenerated by division of
      hematopoietic stem cells (HSCs) into differentiated effector cells. Classically,
      HSCs were thought to reside primarily in the bone marrow niche where they
      produced mature progeny that migrated from the marrow to repopulate the
      peripheral immune system. However, emerging evidence has established that
      hematopoietic stem and progenitor cells (HSPCs) are themselves mobile and able to
      repopulate ectopic niches and contribute more directly to inflammatory responses
      in the periphery. How the HSPCs remain immune to destruction in a toxic
      inflammatory milieu is unknown.

PMID- 19769745
TI  - Tumour necrosis factor-alpha attenuates insulin action on phosphoenolpyruvate
      carboxykinase gene expression and gluconeogenesis by altering the cellular
      localization of Foxa2 in HepG2 cells.
AB  - Circulating tumour necrosis factor-alpha (TNFalpha) levels, which are elevated in
      obesity-associated insulin resistance and diabetes, inhibit insulin signalling at
      several points in the signalling cascade. The liver is critical in maintaining
      circulating glucose levels and, in a preliminary investigation using the human
      hepatoma (HepG2) cell line in this study, we demonstrated the role of TNFalpha in
      the regulation of this phenomenon and determined the underlying molecular
      mechanisms. As the transcription factor Foxa2 has been implicated, in part, in
      the regulation of gluconeogenic genes, we studied the effects of TNFalpha and/or
      insulin on its cellular status in hepatocytes, followed by an assessment of its
      occupancy on the phosphoenolpyruvate carboxykinase (PEPCK) promoter.
      Preincubation of cells with TNFalpha, followed by insulin, significantly
      prevented insulin-mediated nuclear exclusion of Foxa2 and substantially increased
      its nuclear concentration. Foxa2 was subsequently found to occupy its binding
      element on the PEPCK promoter. TNFalpha alone, however, did not alter the status
      of cellular Foxa2 or its occupancy on the PEPCK promoter. TNFalpha preincubation
      also significantly attenuated insulin-induced inhibition of the expression of
      gluconeogenic enzymes and hepatic glucose production. Insulin inhibition of PEPCK
      expression and the preventive effect of TNFalpha could be partially but
      significantly restored in the presence of Foxa2 siRNA. Several other well-known
      mediators of insulin action in the liver in general and of gluconeogenic genes in
      particular include Foxo1, PGC-1 and SREBP-1c. Our results indicate that another
      transcription factor, Foxa2, is at least partly responsible for the attenuating
      effect of TNFalpha on insulin action on PEPCK expression and glucose production
      in HepG2 cells.

PMID- 19769746
TI  - X-ray crystal structures of Phanerochaete chrysosporium Laminarinase 16A in
      complex with products from lichenin and laminarin hydrolysis.
AB  - The 1,3(4)-beta-D-glucanases of glycoside hydrolase family 16 provide useful
      examples of versatile yet specific protein-carbohydrate interactions. In the
      present study, we report the X-ray structures of the 1,3(4)-beta-D-glucanase
      Phanerochaete chrysosporium Laminarinase 16A in complex with beta-glucan products
      from laminarin (1.6 A) and lichenin (1.1 A) hydrolysis. The G6G3G3G glucan, in
      complex with the enzyme, showed a beta-1,6 branch in the acceptor site. The G4G3G
      ligand-protein complex showed that there was no room for a beta-1,6 branch in the
      -1 or -2 subsites; furthermore, the distorted residue in the -1 subsite and the
      glucose in the -2 subsite required a beta-1,3 bond between them. These are the
      first X-ray crystal structures of any 1,3(4)-beta-D-glucanase in complex with
      glucan products. They provide details of both substrate and product binding in
      support of earlier enzymatic evidence.

PMID- 19769747
TI  - Identification of structural determinants for inhibition strength and specificity
      of wheat xylanase inhibitors TAXI-IA and TAXI-IIA.
AB  - Triticum aestivum xylanase inhibitor (TAXI)-type inhibitors are active against
      microbial xylanases from glycoside hydrolase family 11, but the inhibition
      strength and the specificity towards different xylanases differ between TAXI
      isoforms. Mutational and biochemical analyses of TAXI-I, TAXI-IIA and Bacillus
      subtilis xylanase A showed that inhibition strength and specificity depend on the
      identity of only a few key residues of inhibitor and xylanase [Fierens K et al.
      (2005) FEBS J 272, 5872-5882; Raedschelders G et al. (2005) Biochem Biophys Res
      Commun335, 512-522; Sorensen JF & Sibbesen O (2006) Protein Eng Des Sel 19, 205
      210; Bourgois TM et al. (2007) J Biotechnol 130, 95-105]. Crystallographic
      analysis of the structures of TAXI-IA and TAXI-IIA in complex with glycoside
      hydrolase family 11 B. subtilis xylanase A now provides a substantial explanation
      for these observations and a detailed insight into the structural determinants
      for inhibition strength and specificity. Structures of the xylanaseinhibitor
      complexes show that inhibition is established by loop interactions with active
      site residues and substrate-mimicking contacts in the binding subsites. The
      interaction of residues Leu292 of TAXI-IA and Pro294 of TAXI-IIA with the -2
      glycon subsite of the xylanase is shown to be critical for both inhibition
      strength and specificity. Also, detailed analysis of the interaction interfaces
      of the complexes illustrates that the inhibition strength of TAXI is related to
      the presence of an aspartate or asparagine residue adjacent to the acid/base
      catalyst of the xylanase, and therefore to the pH optimum of the xylanase. The
      lower the pH optimum of the xylanase, the stronger will be the interaction
      between enzyme and inhibitor, and the stronger the resulting inhibition.

PMID- 19769748
TI  - Editor's Choice. 19th World Congress of Gynecology and Obstetrics in Cape Town,
      South Africa.

PMID- 19769749
TI  - Induced termination of pregnancy and low birthweight and preterm birth: a
      systematic review and meta-analyses.
AB  - BACKGROUND: History of induced termination of pregnancy (I-TOP) is suggested as a
      precursor for infant being born low birthweight (LBW), preterm (PT) or small for
      gestational age (SGA). Infection, mechanical trauma to the cervix leading to
      cervical incompetence and scarred tissue following curettage are suspected
      mechanisms. OBJECTIVE: To systematically review the risk of an infant being born
      LBW/PT/SGA among women with history of I-TOP. SEARCH STRATEGY: Medline, Embase,
      CINAHL and bibliographies of identified articles were searched for English
      language studies. SELECTION CRITERIA: Studies reporting birth outcomes to mothers
      with or without history of induced abortion were included. DATA COLLECTION: and
      analyses Two reviewers independently collected data and assessed the quality of
      the studies for biases in sample selection, exposure assessment, confounder
      adjustment, analytical, outcome assessments and attrition. Meta-analyses were
      performed using random effect model and odds ratio (OR), weighted mean difference
      and 95% confidence interval (CI) were calculated. MAIN RESULTS: Thirty-seven
      studies of low-moderate risk of bias were included. A history of one I-TOP was
      associated with increased unadjusted odds of LBW (OR 1.35, 95% CI 1.20-1.52) and
      PT (OR 1.36, 95% CI 1.24-1.50), but not SGA (OR 0.87, 95% CI 0.69-1.09). A
      history of more than one I-TOP was associated with LBW (OR 1.72, 95% CI 1.45
      2.04) and PT (OR 1.93, 95% CI 1.28-2.71). Meta-analyses of adjusted risk
      estimates confirmed these findings. CONCLUSIONS: A previous I-TOP is associated
      with a significantly increased risk of LBW and PT but not SGA. The risk increased
      as the number of I-TOP increased.

PMID- 19769750
TI  - Maternal human parvovirus B19 infection and the risk of fetal death and low
      birthweight: a case-control study within 35 940 pregnant women.
AB  - OBJECTIVES: To assess the association between maternal parvovirus B19 infection
      and fetal death, birthweight and length of gestation. DESIGN: Case-control study.
      SETTING: Population based. POPULATION: Cases were all 281 women with fetal death
      within a cohort of 35 940 pregnant woxmen in Norway. The control group consisted
      of a random sample of 957 women with a live born child. METHOD: Information on
      pregnancy outcome was obtained from the Medical Birth Registry of Norway. First
      trimester serum samples were tested for antibodies against parvovirus B19 (IgM
      and IgG). In seronegative women, further serum was analysed to detect
      seroconversion during pregnancy. MAIN OUTCOME MEASURES: Fetal death, length of
      gestation and birthweight. RESULTS: Two of 281 (0.7%) of the women who
      experienced fetal death and nine of 957 (0.9%) of the controls had presence of
      IgM antibodies, crude odds ratio 0.8; 95% CI (0.2-3.5). In initially,
      seronegative women, 3.1% (2/65) with fetal death and 2.6% (8/307) with a live
      birth seroconverted, crude odds ratio 1.2; 95% CI (0.2-5.7). Presence of maternal
      parvovirus-specific IgG or IgM antibodies in the first trimester, or
      seroconversion during pregnancy were not associated with lower birthweight or
      reduced length of gestation in live born children, but was associated with low
      birthweight in stillborn offspring. CONCLUSION: Maternal parvovirus B19 infection
      was not associated with fetal death in our study. Very few cases of fetal death
      may be attributed to maternal parvovirus B19 infection.

PMID- 19769751
TI  - Prospective randomised trial comparing gonadotrophin-releasing hormone analogues
      with triple tourniquets at open myomectomy.

PMID- 19769753
TI  - Evaluation of postpartum blood loss after misoprostol-induced labour.

PMID- 19769754
TI  - Evaluation of postpartum blood loss after misoprostol-induced labour.

PMID- 19769757
TI  - Evaluation of postpartum blood loss after misoprostol-induced labour.

PMID- 19769758
TI  - Management of placenta accreta.

PMID- 19769760
TI  - Optimal management strategies for placenta accreta.

PMID- 19769762
TI  - The best way to determine the best way to undertake a hysterectomy.

PMID- 19769763
TI  - Free and informed choice in medical treatment: making it safe to choose for
      Jehovah's witnesses.

PMID- 19769764
TI  - Agreement on cardiotocogram interpretation and clinical decision using the STAN
      guidelines.

PMID- 19769766
TI  - Tuberculosis in pregnancy in the UK.

PMID- 19769768
TI  - Medical students' experience of vaginal examinations of anaesthetized women.

PMID- 19769776
TI  - A new transcutaneous energy transmission system with hybrid energy coils for
      driving an implantable biventricular assist device.
AB  - We have developed a new transcutaneous energy transmission (TET) system for a
      totally implantable biventricular assist device (BVAD) system in the New Energy
      and Industrial Development Organization (NEDO) artificial heart project. The TET
      system mainly consists of an energy transmitter, a hybrid energy coil unit, an
      energy receiver, an internal battery system, and an optical telemetry system. The
      hybrid energy coil unit consists of an air-core energy transmission coil and an
      energy-receiving coil having a ferrite core. Internal units of the TET system are
      encapsulated in a titanium alloy casing, which has a size of 111 mm in width, 73
      mm in length, and 25 mm in height. In in vitro experiments, the TET system can
      transmit a maximum electric energy of 60 Watts, and it has a maximum transmission
      efficiency of 87.3%. A maximum surface temperature of 46.1 degrees C was measured
      at the ferrite core of the energy-receiving coil during an energy transmission of
      20 Watts in air. The long-term performance test shows that the TET system has
      been able to operate stably for over 4 years with a decrease of energy
      transmission efficiency from 85% to 80%. In conclusion, the TET system with the
      hybrid energy coil can overcome the drawback of previously reported TET systems,
      and it promises to be the highest performance TET system in the world.

PMID- 19769777
TI  - Progressive stroke in pontine infarction.
AB  - OBJECTIVE: The pathogenesis of isolated pontine infarctions is still unclear,
      being attributed both to small or large vessel disease. The extension of
      infarcted tissue to the pons surface has been indicated as a possible marker of
      basilar branch atheromatous disease and some neuroimaging evidence confirms this
      finding. METHODS: On the basis of Kim's et al., study, we performed a revision of
      the literature addressing this topic. RESULTS: Several authors confirm an
      association between basilar artery branch disease and isolated pontine
      infarction; moreover, the enlargement of pontine lesion seems to be associated
      with neurological worsening. We therefore performed a brief analysis of possible
      mechanisms of progression. CONCLUSIONS: Prospective studies could be useful to
      evaluate predictors of neurological worsening in pontine stroke. Improvement of
      neuroimaging techniques is needed for a deeper comprehension of the
      etiopathogenesis of isolated pontine infarction.

PMID- 19769778
TI  - Effect of high-dose methylprednisolone treatment on Th17 cells in patients with
      multiple sclerosis in relapse.
AB  - OBJECTIVES: Growing evidences have suggested that Th17 cells are involved in the
      pathogenic mechanisms of multiple sclerosis (MS). Treatment with high-dose
      intravenous methylprednisolone (IVMP) has beneficial effects on functional
      recovery in patients with MS during relapse. The present study was designed to
      analyze the influences of IVMP on Th17 cells in patients with MS after a 5-day
      high-dose IVMP treatment. MATERIALS AND METHODS: Th17 cell count and the
      production of IL-17 in peripheral blood mononuclear cells (PBMCs) were measured
      using flow cytometry and ELISA respectively. Quantitative real-time PCR was
      performed to analyze the mRNA expression of Th17 cell-related factors (IL-17,
      RORc and IL-23R) in PBMCs. RESULTS: A significant reduction in IL-17 production
      and Th17 cells count in PBMCs was found in patients with MS after IVMP treatment.
      Moreover, the expression of IL-17, IL-23R and RORc mRNA decreased significantly
      after IVMP treatment. CONCLUSIONS: Treatment with methylprednisolone has a
      suppressive effect on Th17 cells and may be related to its clinical efficiency.

PMID- 19769779
TI  - Editorial: From measured behavior to etiology.

PMID- 19769781
TI  - Musings on genome medicine: the Obama effect redux.
AB  - From the point of view of genome medicine, Barack Obama has made two vital policy
      decisions: he has chosen a new director of the National Institutes of Health, and
      his proposed change in United States healthcare policy will have profound effects
      on genome medicine and, indeed, all of academic medicine.

PMID- 19769782
TI  - Bench-to-bedside review: Diaphragm muscle function in disuse and acute high-dose
      corticosteroid treatment.
AB  - Critically ill patients may require mechanical ventilatory support and short-term
      high-dose corticosteroid to treat some specific underlying disease processes.
      Diaphragm muscle inactivity induced by controlled mechanical ventilation produces
      dramatic alterations in diaphragm muscle structure and significant losses in
      function. Although the exact mechanisms responsible for losses in diaphragm
      muscle function are still unknown, recent studies have highlighted the importance
      of proteolysis and oxidative stress. In experimental animals, short-term
      strategies that maintain partial diaphragm muscle neuromechanical activation
      mitigate diaphragmatic force loss. In animal models, studies on the influence of
      combined controlled mechanical ventilation and short-term high-dose
      methylprednisolone have given inconsistent results in regard to the effects on
      diaphragm muscle function. In the critically ill patient, further research is
      needed to establish the prevalence and mechanisms of ventilator-induced diaphragm
      muscle dysfunction, and the possible interaction between mechanical ventilation
      and the administration of high-dose corticosteroid. Until then, in caring for
      these patients, it is imperative to allow partial activation of the diaphragm,
      and to administer the lowest dose of corticosteroid for the shortest duration
      possible.

PMID- 19769783
TI  - Retention, retention, retention: targeting the young in CPR skills training!
AB  - The usefulness of basic cardiopulmonary resuscitation (CPR) training in school
      systems has been questioned, considering that young students may not have the
      physical or cognitive skills required to perform complex tasks correctly. In the
      study conducted by Fleishhackl and coworkers, students as young as 9 years were
      able to successfully and effectively learn basic CPR skills, including automated
      external defibrillator deployment, correct recovery position, and emergency
      calling. As in adults, physical strength may limit the depth of chest
      compressions and ventilation volumes given by younger individuals with low body
      mass index; however, skill retention is good. Training all persons across an
      entire community in CPR may have a logarithmic improvement in survival rates for
      out-of-hospital cardiac arrest because bystanders, usually family members, are
      more likely to know CPR and can perform it immediately, when it is
      physiologically most effective. Training captured audiences of trainees, such as
      the entire work-force of the community or the local school system, are excellent
      mechanisms to help achieve that goal. In addition to better retention with new
      half hour training kits, a multiplier effect can be achieved through school
      children. In addition, early training not only sets the stage for subsequent
      training and better retention, but it also reinforces the concept of a social
      obligation to help others.

PMID- 19769784
TI  - Recent advances in systemic therapy for breast cancer: new technologies for a new
      era.

PMID- 19769785
TI  - The adrenocorticotropic hormone-induced cortisol response in acute pancreatitis.
AB  - The evidence that severe acute pancreatitis can result in critical illness
      related corticosteroid insufficiency following impaired adrenal secretion is
      accumulating. The study by Peng and coworkers in Critical Care certainly
      contributes to that idea, even though the question whether relative adrenal
      insufficiency should prompt for treatment by substitution doses of
      corticosteroids remains unresolved. The study is discussed in terms of the risk
      factors, circumstances and significance of impaired corticosteroid secretion by
      adrenals in severe acute pancreatitis.

PMID- 19769786
TI  - Q&A: What have we found out about the influenza A (H1N1) 2009 pandemic virus?

PMID- 19769787
TI  - The 'stem cell' concept: is it holding us back?
AB  - Developmental biology, regenerative medicine and cancer biology are increasingly
      occupied with the molecular characterization of stem cells. Yet recent work adds
      to a growing body of literature suggesting that 'stemness' cannot be reduced to
      the molecular features of cell types, and is instead an emergent property of cell
      lineages under feedback control.

PMID- 19769788
TI  - A hypothesis-generating search for new genetic breast cancer syndromes--a
      national study in 803 Swedish families.
AB  - Among Swedish families with an inherited predisposition for breast cancer, less
      than one third segregate mutations in genes known to be associated with an
      increased risk of breast cancer in combination with other types of tumours. In a
      search for new putative familial breast cancer syndromes we studied Swedish
      families undergoing genetic counselling during 1992-2000.Four thousand families
      from counselling clinics in Sweden were eligible for study. Families with breast
      cancer only were excluded, as were families with mutations in genes already known
      to be associated with malignant diseases. We identified 803 families with two or
      more cases of breast cancer and at least one other type of cancer. The observed
      proportion of different types of non-breast cancer was compared with the
      percentage distribution of non-breast cancer tumours in Sweden in 1958 and
      1999.We found tumours in the colon, ovary, endometrium, pancreas and liver, as
      well as leukaemia in a significantly larger proportion of the study population
      than in the general population in both years. These tumours were also seen among
      families where several members had one additional tumour, suggesting that
      malignancies at these sites, in combination with breast tumours, could constitute
      genetic syndromes. Endometrial carcinoma has not previously been described in the
      context of breast cancer syndromes and the excess of malignancies at this site
      could not be explained by secondary tumours. Thus, we suggest that endometrial
      carcinoma and breast cancer constitute a new breast cancer syndrome. Further
      investigation is warranted to categorize phenotypes of both breast and
      endometrial tumours in this subgroup.

PMID- 19769791
TI  - Inferring Drosophila gap gene regulatory network: a parameter sensitivity and
      perturbation analysis.
AB  - BACKGROUND: Inverse modelling of gene regulatory networks (GRNs) capable of
      simulating continuous spatio-temporal biological processes requires accurate data
      and a good description of the system. If quantitative relations between genes
      cannot be extracted from direct measurements, an efficient method to estimate the
      unknown parameters is mandatory. A model that has been proposed to simulate
      spatio-temporal gene expression patterns is the connectionist model. This method
      describes the quantitative dynamics of a regulatory network in space. The model
      parameters are estimated by means of model-fitting algorithms. The gene
      interactions are identified without making any prior assumptions concerning the
      network connectivity. As a result, the inverse modelling might lead to multiple
      circuits showing the same quantitative behaviour and it is not possible to
      identify one optimal circuit. Consequently, it is important to address the
      quality of the circuits in terms of model robustness. RESULTS: Here we
      investigate the sensitivity and robustness of circuits obtained from reverse
      engineering a model capable of simulating measured gene expression patterns. As a
      case study we use the early gap gene segmentation mechanism in Drosophila
      melanogaster. We consider the limitations of the connectionist model used to
      describe GRN Inferred from spatio-temporal gene expression. We address the
      problem of circuit discrimination, where the selection criterion within the
      optimization technique is based of the least square minimization on the error
      between data and simulated results. CONCLUSION: Parameter sensitivity analysis
      allows one to discriminate between circuits having significant parameter and
      qualitative differences but exhibiting the same quantitative pattern.
      Furthermore, we show that using a stochastic model derived from a deterministic
      solution, one can introduce fluctuations within the model to analyze the
      circuits' robustness. Ultimately, we show that there is a close relation between
      circuit sensitivity and robustness to fluctuation, and that circuit robustness is
      rather modular than global. The current study shows that reverse engineering of
      GRNs should not only focus on estimating parameters by minimizing the difference
      between observation and simulation but also on other model properties. Our study
      suggests that multi-objective optimization based on robustness and sensitivity
      analysis has to be considered.

PMID- 19769792
TI  - Evidence for a rapid rate of molecular evolution at the hypervariable and
      immunogenic Mycobacterium tuberculosis PPE38 gene region.
AB  - BACKGROUND: PPE38 (Rv2352c) is a member of the large PPE gene family of
      Mycobacterium tuberculosis and related mycobacteria. The function of PPE proteins
      is unknown but evidence suggests that many are cell-surface associated and
      recognised by the host immune system. Previous studies targeting other PPE gene
      members suggest that some display high levels of polymorphism and it is thought
      that this might represent a means of providing antigenic variation. We have
      analysed the genetic variability of the PPE38 genomic region on a cohort of M.
      tuberculosis clinical isolates representing all of the major phylogenetic
      lineages, along with the ancestral M. tuberculosis complex (MTBC) member M.
      canettii, and supplemented this with analysis of publicly available whole genome
      sequences representing additional M. tuberculosis clinical isolates, other MTBC
      members and non tuberculous mycobacteria (NTM). Where possible we have extended
      this analysis to include the adjacent plcABC and PPE39/40 genomic regions.
      RESULTS: We show that the ancestral MTBC PPE38 region comprises 2 homologous PPE
      genes (PPE38 and PPE71), separated by 2 esat-6 (esx)-like genes and that this
      structure derives from an esx/esx/PPE duplication in the common ancestor of M.
      tuberculosis and M. marinum. We also demonstrate that this region of the genome
      is hypervariable due to frequent IS6110 integration, IS6110-associated
      recombination, and homologous recombination and gene conversion events between
      PPE38 and PPE71. These mutations result in combinations of gene deletion, gene
      truncation and gene disruption in the majority of clinical isolates. These
      mutations were generally found to be IS6110 strain lineage-specific, although
      examples of additional within-lineage and even within-cluster mutations were
      observed. Furthermore, we provide evidence that the published M. tuberculosis
      H37Rv whole genome sequence is inaccurate regarding this region. CONCLUSION: Our
      results show that this antigen-encoding region of the M. tuberculosis genome is
      hypervariable. The observation that numerous different mutations have become
      fixed within specific lineages demonstrates that this genomic region is
      undergoing rapid molecular evolution and that further lineage-specific
      evolutionary expansion and diversification has occurred subsequent to the lineage
      defining mutational events. We predict that functional loss of these genes could
      aid immune evasion. Finally, we also show that the PPE38 region of the published
      M. tuberculosis H37Rv whole genome sequence is not representative of the ATCC
      H37Rv reference strain.

PMID- 19769794
TI  - Live cell imaging with protein domains capable of recognizing
      phosphatidylinositol 4,5-bisphosphate; a comparative study.
AB  - BACKGROUND: Phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] is a critically
      important regulatory phospholipid found in the plasma membrane of all eukaryotic
      cells. In addition to being a precursor of important second messengers,
      PtdIns(4,5)P2 also regulates ion channels and transporters and serves the
      endocytic machinery by recruiting clathrin adaptor proteins. Visualization of the
      localization and dynamic changes in PtdIns(4,5)P2 levels in living cells is
      critical to understanding the biology of PtdIns(4,5)P2. This has been mostly
      achieved with the use of the pleckstrin homology (PH) domain of PLCdelta1 fused
      to GFP. Here we report on a comparative analysis of several recently-described
      yeast PH domains as well as the mammalian Tubby domain to evaluate their
      usefulness as PtdIns(4,5)P2 imaging tools. RESULTS: All of the yeast PH domains
      that have been previously shown to bind PtdIns(4,5)P2 showed plasma membrane
      localization but only a subset responded to manipulations of plasma membrane
      PtdIns(4,5)P2. None of these domains showed any advantage over the PLCdelta1PH
      GFP reporter and were compromised either in their expression levels, nuclear
      localization or by causing peculiar membrane structures. In contrast, the Tubby
      domain showed high membrane localization consistent with PtdIns(4,5)P2 binding
      and displayed no affinity for the soluble headgroup, Ins(1,4,5)P3. Detailed
      comparison of the Tubby and PLCdelta1PH domains showed that the Tubby domain has
      a higher affinity for membrane PtdIns(4,5)P2 and therefore displays a lower
      sensitivity to report on changes of this lipid during phospholipase C activation.
      CONCLUSION: These results showed that both the PLCdelta1PH-GFP and the GFP-Tubby
      domain are useful reporters of PtdIns(4,5)P2 changes in the plasma membrane, with
      distinct advantages and disadvantages. While the PLCdelta1PH-GFP is a more
      sensitive reporter, its Ins(1,4,5)P3 binding may compromise its accuracy to
      measure PtdIns(4,5)P2 changes. The Tubby domain is more accurate to report on
      PtdIns(4,5)P2 but its higher affinity and lower sensitivity may limit its utility
      when phospholipase C activation is only moderate. These studies also demonstrated
      that similar changes in PtdIns(4,5)P2 levels in the plasma membrane can
      differentially regulate multiple effectors if they display different affinities
      to PtdIns(4,5)P2.

PMID- 19769793
TI  - Variation in the UCP2 and UCP3 genes associates with abdominal obesity and serum
      lipids: the Finnish Diabetes Prevention Study.
AB  - BACKGROUND: We explored the associations of three variants in the uncoupling
      protein 2 (UCP2) gene, one variant in the UCP2-UCP3 intergenic region and five
      variants in the uncoupling protein 3 (UCP3) gene with obesity and diabetes
      related traits in subjects with impaired glucose tolerance participating in
      Finnish Diabetes Prevention Study. Altogether 507 overweight individuals (body
      mass index: 31.2 +/- 4.5 kg/m2, age: 55 +/- 7 years) for whom DNA was available
      were randomized to either an intensified diet and physical activity group or to a
      conventional care control group. METHODS: We analysed the data from the baseline
      and annual follow-up visits from years 1, 2 and 3. Measurements of anthropometry,
      plasma glucose and serum insulin in oral glucose tolerance test, serum total
      cholesterol, HDL-cholesterol and triglycerides were included. The median follow
      up time for type 2 diabetes incidence was 7 years. Genetic variants were screened
      by restriction fragment length polymorphism or Illumina method. RESULTS: UCP3
      gene variant rs3781907 was associated with increased serum total and LDL
      cholesterol levels, at baseline and during the follow-up period. The same variant
      was associated with a higher risk of type 2 diabetes. Variants rs1726745,
      rs11235972 and rs1800849 in the UCP3 gene associated with serum total and LDL
      cholesterol at baseline. Haploblock including variants rs659366, rs653529,
      rs15763, and rs1726745 was associated with measures of abdominal obesity at
      baseline and in the longitudinal analysis. The haplotype comprising alleles
      rs659366-G, rs653529-A, rs15763-G and rs1726745-A was associated with higher
      waist-to-hip ratio, and haplotype comprising alleles rs3781907-G, rs11235972-A,
      and rs1800849-T was associated with increased serum total and LDL-cholesterol
      concentrations. CONCLUSION: Genetic variation in the UCP2-UCP3 gene cluster may
      act as a modifier increasing serum lipid levels and indices of abdominal obesity,
      and may thereby also contribute to the metabolic aberrations observed in obesity
      and type 2 diabetes.

PMID- 19769796
TI  - Does a neuropsychological index of hemispheric lateralization predict onset of
      upper respiratory tract infectious symptoms?
AB  - OBJECTIVES: Past studies demonstrate relationships between hemispheric
      lateralization (HL) and immunity. However, the relevance of HL-immune
      relationships to health and illness has rarely been investigated. This study
      tested whether a neuropsychological index of right-hemispheric lateralization
      (right-HL) predicts development of upper respiratory tract infectious (URTI)
      symptoms. DESIGN: We used a prospective, matched, case-control design. METHODS:
      Initially, 80 URTI symptom free adults underwent neuropsychological assessment
      including right-HL (picture vs. word recognition), and were then followed-up
      during 10 weeks for development of URTI symptoms and objective signs of URTI.
      Participants reporting URTI symptoms (Ill; N=21) were matched on age, gender, and
      IQ with 21 participants remaining well. RESULTS: At baseline, the right-HL index
      was significantly higher in participants who later became ill (9.9%) compared to
      well participants (3.9%, p<.05). Health behaviour also predicted URTI symptoms.
      In a logistic regression, right-HL significantly predicted self-reported URTI,
      independent of health behaviour and neuroticism. CONCLUSIONS: Greater right-HL
      predicted URTI symptom development during follow-up, independent of important
      confounders. These findings expand previous HL-immune relationships to a common
      immune-related illness.

PMID- 19769797
TI  - Are organ donation communication decisions reasoned or reactive? A test of the
      utility of an augmented theory of planned behaviour with the
      prototype/willingness model.
AB  - OBJECTIVES: To explore whether people's organ donation consent decisions occur
      via a reasoned and/or social reaction pathway. DESIGN: We examined prospectively
      students' and community members' decisions to register consent on a donor
      register and discuss organ donation wishes with family. METHOD: Participants
      completed items assessing theory of planned behaviour (TPB; attitude, subjective
      norm, perceived behavioural control (PBC)), prototype/willingness model (PWM;
      donor prototype favourability/similarity, past behaviour), and proposed
      additional influences (moral norm, self-identity, recipient prototypes) for
      registering (N=339) and discussing (N=315) intentions/willingness. Participants
      self-reported their registering (N=177) and discussing (N=166) behaviour 1 month
      later. The utility of the (1) TPB, (2) PWM, (3) augmented TPB with PWM, and (4)
      augmented TPB with PWM and extensions was tested using structural equation
      modelling for registering and discussing intentions/willingness, and logistic
      regression for behaviour. RESULTS: While the TPB proved a more parsimonious
      model, fit indices suggested that the other proposed models offered viable
      options, explaining greater variance in communication intentions/willingness. The
      TPB, augmented TPB with PWM, and extended augmented TPB with PWM best explained
      registering and discussing decisions. The proposed and revised PWM also proved an
      adequate fit for discussing decisions. Respondents with stronger intentions (and
      PBC for registering) had a higher likelihood of registering and discussing.
      CONCLUSIONS: People's decisions to communicate donation wishes may be better
      explained via a reasoned pathway (especially for registering); however,
      discussing involves more reactive elements. The role of moral norm, self
      identity, and prototypes as influences predicting communication decisions were
      highlighted also.

PMID- 19769795
TI  - Revisiting the Plasmodium falciparum RIFIN family: from comparative genomics to
      3D-model prediction.
AB  - BACKGROUND: Subtelomeric RIFIN genes constitute the most abundant multigene
      family in Plasmodium falciparum. RIFIN products are targets for the human immune
      response and contribute to the antigenic variability of the parasite. They are
      transmembrane proteins grouped into two sub-families (RIF_A and RIF_B). Although
      recent data show that RIF_A and RIF_B have different sub-cellular localisations
      and possibly different functions, the same structural organisation has been
      proposed for members of the two sub-families. Despite recent advances, our
      knowledge of the regulation of RIFIN gene expression is still poor and the
      biological role of the protein products remain obscure. RESULTS: Comparative
      studies on RIFINs in three clones of P. falciparum (3D7, HB3 and Dd2) by
      Multidimensional scaling (MDS) showed that gene sequences evolve differently in
      the 5'upstream, coding, and 3'downstream regions, and suggested a possible role
      of highly conserved 3' downstream sequences. Despite the expected polymorphism,
      we found that the overall structure of RIFIN repertoires is conserved among
      clones suggesting a balance between genetic drift and homogenisation mechanisms
      which guarantees emergence of novel variants but preserves the functionality of
      genes. Protein sequences from a bona fide set of 3D7 RIFINs were submitted to
      predictors of secondary structure elements. In contrast with the previously
      proposed structural organisation, no signal peptide and only one transmembrane
      helix were predicted for the majority of RIF_As. Finally, we developed a strategy
      to obtain a reliable 3D-model for RIF_As. We generated 265 possible structures
      from 53 non-redundant sequences, from which clustering and quality assessments
      selected two models as the most representative for putative RIFIN protein
      structures. CONCLUSION: First, comparative analyses of RIFIN repertoires in
      different clones of P. falciparum provide insights on evolutionary mechanisms
      shaping the multigene family. Secondly, we found that members of the two sub
      families RIF_As and RIF_Bs have different structural organization in accordance
      with recent experimental results. Finally, representative models for RIF_As have
      an "Armadillo-like" fold which is known to promote protein-protein interactions
      in diverse contexts.

PMID- 19769798
TI  - Loratadine and montelukast administered in combination produce decongestion in an
      experimental feline model of nasal congestion.
AB  - BACKGROUND: Histamine and leukotrienes act to exert numerous local and systemic
      effects that contribute to the pathophysiology of allergic rhinitis. The aim of
      these experiments was to evaluate the nasal decongestant effects of loratadine
      and montelukast alone and in combination in a feline model of nasal congestion.
      We also studied the decongestant actions of the alpha-agonist adrenergic agonist
      D-pseudoephedrine with and without desloratadine. METHODS: Acoustic rhinometry
      was used to determine nasal cavity dimensions after intranasal compound 48/80.
      Cats were given D-pseudoephedrine (0.3 mg/kg) alone or in combination with
      desloratadine (5 mg/kg) 1 hour before nasal provocation with compound 48/80 (1%,
      75 microliters) to either the left or right nasal passageway. Using a similar
      design, the nasal decongestant effects of montelukast (1 mg/kg) and loratadine
      (10 mg/kg) were studied alone and in combination. RESULTS: The addition of
      desloratadine to D-pseudoephedrine did not improve decongestant efficacy compared
      with each drug given individually. In contrast, when montelukast (1 mg/kg) was
      given in combination with loratadine (10 mg/kg), the decongestant activity was
      greater than when these drugs were administered separately. Sixty minutes after
      compound 48/80 provocation the nasal cavity volume ratio (volume ratio of the
      compound 48/80 treated/untreated nasal passageway) for the control, montelukast
      alone, loratadine alone, and the montelukast plus loratadine-treated groups were
      0.20 +/- 0.03, 0.24 +/- 0.01, 0.28 +/- 0.03, and 0.50 +/- 0.03. CONCLUSION:
      Concomitant montelukast plus loratadine produces a greater degree of nasal
      decongestion compared with montelukast or loratadine alone in an experimental
      model of nasal congestion.

PMID- 19769799
TI  - Acupuncture for nasal congestion: a prospective, randomized, double-blind,
      placebo-controlled clinical pilot study.
AB  - BACKGROUND: Nasal congestion is one of the most common complaints dealt with in
      otorhinolaryngology. Side effects of decongestants are frequently seen in
      patients with chronic nasal congestion. This leads to an increasing demand of
      alternative treatments such as acupuncture. Future studies on acupuncture should
      aim at objectifying effects by both physical measuring and double blinding.
      Therefore, we were interested in whether these effects can potentially be
      measured as increase in nasal airflow (NAF) in ventus ("wind") disease of
      traditional Chinese medicine (TCM). METHODS: Twenty-four patients with a history
      of nasal congestion due to hypertrophic inferior turbinates or chronic sinusitis
      without polyposis were additionally diagnosed according to the Heidelberg model
      of TCM. They were asked to score the severity of their nasal congestion on a
      visual analog scale (VAS). The acupuncturist was blinded according to the
      Heidelberg blinding assay. NAF was measured by using active anterior
      rhinomanometry (ARM). Specific verum acupoints according to the Chinese medical
      diagnosis were tested against nonspecific control acupoints. VAS and NAF were
      scored and measured before and 15 and 30 minutes after acupuncture. RESULTS:
      Control acupuncture showed a significant improvement in VAS and a deterioration
      of NAF. Verum acupuncture showed highly significant improvements in VAS and NAF.
      In addition, verum acupuncture improved NAF and VAS significantly over time.
      CONCLUSION: Our control and verum acupoints fulfill the condition of a control
      and verum treatment, respectively. Measuring NAF by RRM and scoring VAS are
      possible and reflect acupuncture effects in vivo.

PMID- 19769800
TI  - Cigarette smoke extract stimulates interleukin-8 production in human airway
      epithelium and is attenuated by superoxide dismutase in vitro.
AB  - BACKGROUND: Cigarette smoke exposure (CSE) results in extensive inflammation in
      the upper and lower airways. Reactive oxygen species, such as superoxide, have
      been shown to be potent mediators of this inflammation. METHODS: Mucosal biopsy
      specimens were collected from patients undergoing sinonasal surgery and were used
      as a source of primary epithelial cells. Human sinonasal epithelial (HSNE) cells
      and were isolated from sinus tissue, maintained in culture, and ultimately
      treated with varying concentrations of CSE with or without free superoxide
      dismutase (SOD). Supernatants and cell lysates were examined for the
      proinflammatory cytokine interleukin (IL)-8. Similar experiments were performed
      using normal human bronchial epithelial (NHBE) cell lines. RESULTS: CSE induces
      both secretion and intracellular production of the proinflammatory cytokine IL-8
      by HSNE cells in a dose-dependent manner. Furthermore, this up-regulation can be
      suppressed by SOD. CSE induces secretion of IL-8 in NHBEs that is also suppressed
      by SOD. CONCLUSION: Inflammation in the airway after CSE can be blocked by SOD in
      this in vitro model. The ability to attenuate CSE-induced inflammation with SOD
      could provide a therapeutic/preventative approach for individuals with cigarette
      smoke exposure.

PMID- 19769801
TI  - Chinook wind barosinusitis: an anatomic evaluation.
AB  - BACKGROUND: Chinook, or fohn, is a weather phenomenon characterized by a rapid
      influx of warm, high-pressured winds into a specific location. Pressure changes
      associated with chinook winds induce facial pain similar to acute sinusitis. The
      purpose of this study was to determine the relationship between sinonasal anatomy
      and chinook headaches. METHODS: Retrospective computed tomography (CT) sinonasal
      anatomy analysis of 38 patients with chinook headaches and 27 controls (no
      chinook headaches). The chinook headache status was blinded from the CT reviewer.
      Forty-one sinonasal anatomy variants, Lund-Mackay status, and sinus size (cm(3))
      were recorded. RESULTS: There were three statistically significant sinonasal
      anatomy differences between patients with and without chinook headaches. The
      presence of a concha bullosa and sphenoethmoidal cell (Onodi cell) appeared to
      predispose to chinook headaches (p = 0.004). Chinook headache patients had larger
      maxillary sinus size (right, p = 0.015, and left, p = 0.002). The Lund-Mackay
      score was higher in the control patients (p = 0.003) indicating that chronic
      sinusitis does not play a role in chinook headaches. CONCLUSION: Chinook winds
      are a common source of facial pain and pressure. This is the first study to show
      that sinonasal anatomic variations may be a predisposing factor. Anatomic
      variants may induce facial pain by blocking the natural sinus ostia, thus
      preventing adequate pressure equilibrium.

PMID- 19769802
TI  - Cigarette smoke extract enhances rhinovirus-induced toll-like receptor 3
      expression and interleukin-8 secretion in A549 cells.
AB  - BACKGROUND: Using A549 alveolar epithelial type II-like cells, we investigated
      the effects of cigarette smoke on the expression of rhinovirus (RV)-induced Toll
      like receptor (TLR) 3, interleukin (IL)-6, and IL-8 secretion and viral
      replication. METHODS: Cigarette smoke extract (CSE) was prepared by smoking two
      commercial cigarettes with filters (0.9-mg of nicotine and 8.5-mg of tar per
      cigarette). Cells were infected with RV serotype 16 (RV-16) and cultured for 2
      days (RV group), pretreated with 1, 2.5, or 5% CSE for 1 day before RV infection,
      and culture with CSE for 2 days after infection (RV plus CSE group), or were
      cultured in medium for 3 days (control group), treated with 1, 2.5, or 5% CSE for
      3 days (CSE group). Changes in TLR3, IL-6, and IL-8 mRNA expression were assayed
      by real-time polymerase chain reaction and TLR3 protein expression were assessed
      by flow cytometry; IL-6 and IL-8 secretions were measured by ELISA; and RV
      replication was assessed by viral culture. RESULTS: CSE increased RV-induced TLR3
      expression and RV-induced IL-8 secretion at lower concentrations in A549 cells.
      On the contrary, CSE dose dependently inhibited RV-induced IL-6 secretions and
      had no effect on RV replications. CONCLUSION: Our results suggest that cigarette
      smoke may potentiate viral common cold symptoms by enhancing IL-8 secretion at
      lower concentrations, but not by increasing viral replication.

PMID- 19769803
TI  - Urgent carotid endarterectomy for patients with unstable symptoms: systematic
      review and meta-analysis of outcomes.
AB  - Current evidence suggests that carotid endarterectomy (CEA) performed within 2
      weeks of symptoms produces better long-term results than if it is delayed. Urgent
      endarterectomy following unstable presentations such as crescendo transient
      ischemic attack (cTIA) or progressive stroke has been associated with variable
      results. The evidence for this treatment strategy required reviewing. A
      systematic review of articles related to urgent CEA between 1980 and 2008 was
      performed. For cTIA, there was an odds ratio of 5.6 (95% confidence interval 3.3
      9.7, p < or = .0001) for combined stroke or death compared with surgery for
      "standard" indications. For unstable stroke, the odds ratio was 5.5 (95%
      confidence interval 3.1-9.3, p < or = .0001). Patients with unstable neurologic
      presentations are at higher risk of complications if operated on urgently.
      Clearer definitions would help more precise patient selection to avoid
      inadvertently operating on patients with an unacceptably high risk of poor
      outcome.

PMID- 19769804
TI  - Review of current theories for abdominal aortic aneurysm pathogenesis.
AB  - Atherosclerotic plaques are a feature of abdominal aortic aneurysms (AAAs).
      Atherosclerosis and AAA appear to share similar risk factors. These observations
      have led to the conclusion that AAAs are a consequence of advanced
      atherosclerosis.This review explores current theories regarding the pathogenesis
      of AAA and their implications for treatment.A systematic literature search was
      conducted using the search terms abdominal aortic aneurysm, atherosclerosis,
      pathogenesis, and systemic disease. Articles were categorized according to the
      association of AAAs with atherosclerosis, arteriomegaly, peripheral aneurysm,
      systemic expression, genetics, autoimmunity, oxidative stress, and systemic
      disease. Twenty-nine articles reporting changes in the systemic vasculature
      associated with AAA and 12 articles examining the shared risk factor hypothesis
      were identified.There is insufficient evidence to confirm that AAAs are the
      result of advanced atherosclerosis. The bulk of evidence points to AAA disease
      being a systemic disease of the vasculature, with a predetermined genetic
      susceptibility leading to a phenotype governed by environmental factors.

PMID- 19769805
TI  - Ankle peak systolic velocity: new parameter to predict nonhealing in diabetic
      foot lesions.
AB  - The objective of this study was to determine whether ankle peak systolic velocity
      (APSV) can predict nonhealing in diabetic foot lesions. Diabetic patients
      referred for duplex scanning of the lower extremity arteries were included if
      they had foot lesions such as ulcers, gangrene, or tissue necrosis and had no
      palpable pedal pulses. End points were healed or healing foot lesions,
      revascularization, major amputation, or death. One hundred consecutive limbs were
      included. Forty-three limbs with diabetic foot lesions reached the end point of
      adequate healing or complete healing, whereas 57 limbs had nonhealing lesions.
      The APSV was significantly higher in limbs with healed or healing lesions
      compared with limbs with nonhealed lesions: 53.0 cm/s (41.8-81.6) versus 19.2
      cm/s (12.4-26.5), p < .0001. At a cutoff point of 35 cm/s, the APSV showed a
      sensitivity of 92.9% (95% confidence interval [CI] 82-97), a specificity of 90.6%
      (95% CI 76-96), a positive predictive value of 92.9%, and a negative predictive
      value of 90.6% in predicting nonhealing of diabetic foot lesions. There was a
      significant difference between the APSV before and after revascularization: 20.4
      cm/s (12.4-26.3) versus 48.8 cm/s (36.1-80.8), p < .0001. APSV could predict
      nonhealing of diabetic foot lesions with a high degree of accuracy in this group
      of patients.

PMID- 19769807
TI  - Cutdowns for totally implantable access ports to central veins.
AB  - For insertion of totally implantable access ports, with the catheter end in the
      superior vena cava, the percutaneous (Seldinger) technique is commonly used. Of
      cutdowns, the cephalic vein cutdown is the most popular one (success rate about
      80%), followed by the external jugular vein cutdown. Our preliminary experience
      suggests that internal jugular vein and basilic vein cutdowns have the anatomic
      features to prove both of them superior to the cephalic vein cutdown.

PMID- 19769806
TI  - Aortofemoral bypass to bridge end-stage renal disease patients with severe iliac
      calcification to kidney transplantation.
AB  - Patients undergoing hemodialysis have a lower survival rate than those who
      receive a kidney transplant. Mortality among hemodialysis patients is
      approximately 14.5% compared with 1.5% for transplant recipients. One of the
      exclusion criteria for renal transplant is severe iliac artery calcification. We
      performed an aortofemoral bypass in these patients to make them eligible for
      renal transplantation. Eleven patients were selected to receive an aortofemoral
      bypass. All had severe calcification of iliac arteries. Eight patients required a
      bypass from the thoracic aorta and two from the infrarenal level.
      Revascularization was successful in 10 patients. Patency was 100%. Surgery could
      not be performed in one owing to severe calcification of the femoral artery. One
      patient died owing to gastrointestinal bleeding. Two patients developed
      complications; one needed a splenectomy, and the other developed meningitis and
      paralytic ileus. To date, four patients have received transplants, and the
      viability of the transplanted kidney is good in all cases. Renal transplantation
      is the only method known to improve survival and quality of life for hemodialysis
      patients. We consider that if patients with severe iliac calcification are well
      informed of the morbidity and mortality risk of an aortic bypass, this
      intervention can be justified in this setting.

PMID- 19769808
TI  - Percutaneous access with closure devices and iliac extension limbs allows safe
      repair of common iliac artery aneurysm repair as an outpatient procedure.
AB  - The true benefits of endovascular therapy will be realized when treatment for
      common vascular conditions can be performed effectively and safely, with minimal
      morbidity and in a cost-effective manner. We describe three cases of common iliac
      artery aneurysm repair performed as an outpatient procedure without problems.
      This was done in a cost-effective manner and with a high degree of patient
      satisfaction.

PMID- 19769809
TI  - Recanalization of chronic carotid occlusion: case report and review of the
      literature.
AB  - Recanalization of an occluded extracranial internal carotid artery is a rare
      event. The mechanism remains unclear. We report a case of recanalized internal
      carotid artery in its extracranial portion. The patient underwent successful
      carotid endarterectomy.

PMID- 19769810
TI  - Inferior vena cava aneurysm.
AB  - Aneurysms of the inferior vena cava (IVC) are exceedingly rare; less than 50
      cases have been reported in the world literature. Owing to the paucity of data
      regarding the natural history of IVC aneurysms, there is no consensus on their
      treatment. This case report describes the evaluation of an IVC aneurysm in a 56
      year-old male, briefly discusses the embryologic development of the IVC, and
      revisits the question of whether surgical intervention is indicated in these
      patients.

PMID- 19769811
TI  - Hybrid approach for treatment of behind the knee popliteal artery aneurysms.
AB  - We describe herein a combined approach to the treatment of popliteal artery
      aneurysms (PAA) that averts extensive dissections and potential blood loss
      particularly in cases of behind-the-knee aneurysms. Over the last 4 years, 13
      patients (12 males) with mean age of 75 +/- 8 years were treated for PAAs at our
      institution with a combined surgical and endovascular approach. The mean size of
      popliteal aneurysms was 2.9 cm +/- 1.7 cm. One of the 13 cases (8%) was performed
      for acute ischemia and an additional 5 (38%) for claudication. All operations
      were performed under general anesthesia in supine position. Vein conduits (eight
      ipsilateral great saphenous veins, two contralateral great saphenous veins and
      one arm vein) were utilized for 11 bypasses. Of these, eight were from
      superficial femoral artery (SFA) to below the knee popliteal artery, two
      popliteal to popliteal and one SFA to posterior tibial artery. In addition, two
      expanded polytetrafluoroethylene femoral popliteal bypasses were performed. The
      distal anastomosis was performed after the popliteal artery was ligated distal to
      the aneurysm. Next, coil embolization of the aneurysmal sac was performed under
      fluoroscopic or ultrasound guidance. Coils were embolized through a 5F sheath.
      Lastly, the popliteal artery was ligated distal to the proximal anastomosis.
      Completion studies were obtained with duplex in six cases and arteriography in
      the remaining five cases. Mean follow-up was 11.6 months +/- 9.6. One bypass
      occluded in 2 months after surgery. One patient demonstrated continued growth of
      his aneurysm despite coil embolization twice and underwent an open ligation of
      the branches perfusing the aneurysm from within the sac through a posterior
      approach. This approach may be particularly useful for PAAs located behind the
      knee where optimal surgical exposure is often difficult and the collateral
      circulation is abundant. The proposed technique is simple, effective and averts
      extensive dissections required to minimize blood loss.

PMID- 19769812
TI  - Klippel-Trenaunay syndrome: treatment of lower extremity pain with a spinal cord
      stimulator.
AB  - A young adult man with Klippel-Trenaunay syndrome presented to our pain
      management service with complaints of severe lower extremity neuropathic pain
      (pain scale 8 of 10 on the left and 4 of 10 on the right). The pain in his left
      leg was so severe that he wanted to undergo a left lower extremity amputation.
      The patient declined chronic use of narcotic medications for pain relief,
      believing that this would interfere with his educational and lifestyle pursuits.
      After a complete evaluation for possible sources of pain, we performed a trial
      placement of a spinal cord stimulator at the T9 level, which relieved his pain.
      We then placed a stimulator at the T10 level. At 1 year postimplantation, he was
      pain free (pain scale 1 of 10 bilaterally) and was able to function normally
      without narcotic support. We believe this to be the first use of a spinal cord
      stimulator for lower extremity pain resulting from Klippel-Trenaunay syndrome. We
      also discuss the clinical evaluation and treatment of a Klippel-Trenaunay
      syndrome patient with chronic pain.

PMID- 19769813
TI  - Isolated superficial temporal artery dissection masquerading as giant cell
      arteritis.
AB  - A 79-year-old male presented with symptoms suggesting giant cell arteritis (GCA)
      and elevation of acute-phase reactants. Bilateral superficial temporal artery
      (STA) biopsies were negative for GCA. However, the right-sided biopsy showed a
      STA dissection. Spontaneous isolated STA dissection has never been reported
      previously. The pertinent available literature is also discussed.

PMID- 19769815
TI  - Silent sinus syndrome: case series and literature review.

PMID- 19769814
TI  - Use of the Angiojet catheter to remove plaque outside a neuroprotection filter
      during carotid artery stenting.
AB  - Carotid protection devices (CPD) during carotid artery stenting reduce the risk
      of cerebral embolization. The presence of debris outside the filter presents a
      problem as the material may be plaque or thrombus. We report a case that required
      the use of the Angiojet catheter to remove debris outside the CPD.

PMID- 19769816
TI  - Chondromyxoid fibroma of the skull base: case report and review of the
      literature.

PMID- 19769817
TI  - Castleman disease in the parapharyngeal space: unusual presentation and
      differential diagnostic imaging features of the disease.

PMID- 19769818
TI  - Emerging role of Escherichia coli as a deep neck space abscess pathogen in
      immunocompetent children: case report of twins.

PMID- 19769819
TI  - Floor of the mouth epidermoid cyst enlarging after pregnancy.

PMID- 19769820
TI  - Tubercular cervical adenitis: clinicopathologic analysis of 180 cases.
AB  - OBJECTIVE: To analyze the clinical presentations, laboratory investigation
      results, and histopathologic evaluation of tubercular cervical adenitis (TCA) in
      our population. DESIGN: Prospective study. SETTING: Tertiary health care centre.
      PATIENTS AND METHODS: We studied 180 patients with TCA who were managed in the
      Department of Otolaryngology between December 2004 and June 2007. RESULTS: There
      were 76 male patients (42%) and 104 females (58%), with ages ranging from 5 to 58
      years. All patients presented with single or multiple neck swellings.
      Constitutional symptoms such as fever were present in 52 patients (29%), whereas
      cough, weight loss, and reduced appetite were seen in 40 patients (22%). Forty
      seven patients (26%) had bilateral lymph node involvement. Only 23 patients (13%)
      had chest radiographs suggestive of pulmonary tuberculosis. Fine-needle aspirates
      from 168 patients (93%) showed granulomas with caseating necrosis. However, acid
      fast bacilli were seen in only 45 (25%) aspirate smears. Twelve patents (7%)
      required a lymph node biopsy to confirm the diagnosis. CONCLUSION: TCA usually
      presents with multiple lymph node involvement without the constitutional signs
      and symptoms of tuberculosis. The diagnosis is based on a high index of clinical
      suspicion coupled with laboratory and pathologic investigations.

PMID- 19769821
TI  - Does Helicobacter pylori have a role in the development of chronic otitis media
      with effusion? A preliminary study.
AB  - OBJECTIVE: To investigate the possible relationship between chronic otitis media
      with effusion (COME) and Helicobacter pylori (HP). PATIENTS AND METHODS: Twenty
      five patients (7 girls and 18 boys; age range 2-10 years, mean age 7.8 years)
      with COME with or without adenotonsillary disease were included in this study.
      Myringotomy was performed on all patients. Nine patients also underwent
      adenoidectomy, and 10 patients underwent adenotonsillectomy. The adenoidectomy
      specimens and middle ear effusions were examined for HP colonization by the
      Campylobacter-like organism (CLO) test. Adenoidectomy specimens were also
      evaluated for HP using immunohistochemical (IHC) evaluation. Before surgery, anti
      HP immunoglobulin G (IgG) and A (IgA) antibody titres were detected by enzyme
      linked immunosorbent assay in the venous blood samples of the patients. RESULTS:
      The CLO test results were not positive in any of the adenoidectomy specimens and
      middle ear effusions. IHC examination also revealed that none of the adenoid
      tissue specimens had a positive HP result. The anti-HP IgG antibody was detected
      to be positive in eight patients (32%), and IgA antibody was detected in three
      patients (12%). In three patients (12%), both IgA and IgG antibodies were
      positive. CONCLUSION: We were unable to detect the presence of HP in the middle
      ear effusions and adenoid specimens of children with COME. Owing to the small
      size of the group in our study, we propose that further studies be carried out
      with larger study and control groups in an effort to explain the presence of HP
      in middle ear effusions.

PMID- 19769822
TI  - Improvement in otitis media with effusion in patients undergoing tracheostomy
      after prolonged endotracheal intubation.
AB  - OBJECTIVES: Otitis media with effusion (OME) has a higher incidence in adult
      intensive care unit (ICU) patients. This observational study sought to examine
      the effect of tracheostomy on OME in critically ill patients and explore the
      predisposing factors. MATERIALS AND METHODS: Twenty-seven ICU patients who had
      undergone prolonged intubation (more than 14 days) received traditional
      tracheostomies. Otoscopic examination, tympanometry, and spectral gradient
      acoustic reflectometry were performed both at the time of the tracheostomy and 7
      days later. We collected data on the patients' demographics (age and gender),
      underlying diseases, duration of intubation prior to the tracheostomy, history of
      gastroesophageal reflux disease, length of antibiotic use, level of
      consciousness, and presence of nasogastric tubes. RESULTS: At the time of the
      tracheostomy, 25 (46%) ears from 14 (52%) patients were classified as cases of
      OME, 17 (31%) ears and 7 (26%) patients as normal cases, and 12 (11%) ears from 6
      (11%) patients as cases of negative pressure in the tympanic cavity. Seven days
      after the tracheostomy, OME was resolved in 17 (68%) ears and persisted in 6
      (24%) ears, whereas negative pressure developed in 2 (8%) ears. Our data showed
      that the incidence of OME reduced from 46% to 22% after tracheostomy was
      performed on the patients. CONCLUSION: The incidence of OME in adult ICU patients
      who were intubated for more than 14 days was found to reduce after tracheostomy.
      Notably, the rate of improvement in the conscious patients was significantly
      higher than that in the unconscious patients.

PMID- 19769823
TI  - Assessment of submucosal radiofrequency tonsil reduction by magnetic resonance
      imaging.
AB  - OBJECTIVES: The primary objective was to assess the efficacy of submucosal
      radiofrequency tonsil reduction (SRFTR) in adults by magnetic resonance imaging
      (MRI). The secondary objective was to evaluate the morbidity of SRFTR. METHODS: A
      prospective, longitudinal clinical study with a follow-up time of 12 months was
      conducted of 10 consecutive patients with the median age of 24.5 years (range 19
      55 years) with obstructive palatine tonsil hypertrophy. SRFTR was delivered in an
      outpatient setting in a tertiary care centre, academic teaching hospital. MAIN
      OUTCOME MEASURES: The change in tonsillar volume after SRFTR was evaluated with
      MRI by two radiologists independently and blinded to the treatment results. The
      morbidity was assessed with a visual analogue scale (VAS), a questionnaire for
      the pain medication needed, and inflammatory laboratory parameters. VAS and use
      of pain medication results were compared with those of two earlier cohort groups
      undergoing conventional tonsillectomy with two different techniques at our
      department. RESULTS: The tonsil volume reduced significantly with a median
      reduction in the total tonsil volume of 12.6% (range 3.7-41.5%, pretreatment vs
      posttreatment volume, p < .01). VAS of the morbidity symptoms and the amount of
      pain medication needed were significantly lower in the SRFTR group than in the
      two historical tonsillectomy groups. The laboratory parameters showed a
      significant change. CONCLUSION: SRFTR in adults with obstructive palatine tonsil
      hypertrophy is a minimally invasive procedure causing a tonsil volume reduction
      demonstrated by MRI. The procedure seems to be associated with acceptable
      morbidity.

PMID- 19769824
TI  - Radiation-induced xerostomia: is octreotide the solution?
AB  - OBJECTIVE: In this study, we looked for evidence that octreotide, a drug used
      specifically in acromegaly and other digestive pathologies, can have a
      radioprotective effect on salivary glands. This effect has already been proven on
      the pituitary gland, which is why we postulated that octreotide could act the
      same way on rat parotid glands. METHOD: A prospective randomized controlled study
      on animals was conducted. With a noninvasive technique, we collected saliva from
      the parotid glands of 18 anesthetized rats at time 0 (preirradiation) and 1 month
      (postirradiation). Each sampling technique lasted 40 minutes, with pilocarpine
      injection at time 0 and 20 minutes. Saliva was collected bilaterally. Eighteen
      rats, nine in the saline group and nine in the octreotide group, were randomized.
      The substance was injected 30 minutes before irradiation. Thirty gray were given
      with the gamma knife on the left parotid gland of each rat following a
      computerized targeting method. Each gland was examined after the last saliva
      collection to determine the percentage of five criteria: fibrosis, ducts, fat,
      vessels, and acini. RESULTS: Data are available for 17 rats (nine in the
      octreotide group and eight in the saline group). Statistical analysis was done
      with a t-test (independent and paired). We noted that the postirradiation
      secretion in the left (radiated) gland was diminished compared with the right
      (nonradiated) gland in the saline group (p = .014). Fibrosis was increased in the
      irradiated (left) gland in both groups (p = .024 in the octreotide group and p =
      .033 in the saline group). The percentage of duct cells was more important in the
      left (radiated) gland of the octreotide group (p = .046). A trend appeared for a
      decrease in acinic cells only in the control group (p = .063). CONCLUSION:
      Octreotide acted as a radioprotective agent on rat parotid glands 1 month after
      irradiation with 30 Gy given with the gamma knife.

PMID- 19769825
TI  - Ablative free thyroxine to thyroglobulin ratio as a predictor of differentiated
      thyroid cancer recurrence.
AB  - BACKGROUND: Serum thyroglobulin (Tg), a widely used thyroid cancer marker, is
      limited at the time of ablation, unable to differentiate between diseased and
      normal residual tissue. OBJECTIVE: We evaluated the use of the ablation free
      thyroxine to thyroglobulin ratio (fT4:Tg) as a tumour-specific ratio for
      predicting persistence or recurrence in differentiated thyroid cancer. DESIGN:
      Retrospective chart review. SETTING: McGill University Health Centre. METHODS: Of
      234 patients, 84 were analyzed after exclusion of those with anti-Tg antibodies,
      ablation Tg < or = 2, and follow-up < 3 months. Ablation thyroxine and Tg levels
      were recorded and patients were followed to detect recurrence. The relationship
      between the ablation fT4:thyroglobulin ratio and recurrence was evaluated. MAIN
      OUTCOME MEASURES: Hazards ratio (HR) for predictive fT4:Tg ratio cutoff value and
      disease-free survival based on the fT4:Tg ratio. RESULTS: Thirty-eight percent of
      patients developed recurrence: 8 pathologically proven and 24 suspected. Eighty
      one percent of patients with recurrence had an fT4:Tg < 27%, in contrast to 23%
      of those without recurrence (HR 6.2; p < .001). Of all patients with fT4:Tg <
      27%, 68% developed evidence of recurrence compared with 13% with fT4:Tg > or =
      27% (p < .001). Recurrences in the fT4:Tg < 27% group occurred twice as early.
      CONCLUSION: Ablation fT4:Tg < 27% is predictive of recurrence and should be used
      to identify high-risk patients.

PMID- 19769826
TI  - Cost analysis of intraoperative frozen section examinations in thyroid surgery in
      a Canadian tertiary center.
AB  - OBJECTIVE: To perform a cost analysis of the routine intraoperative frozen
      section (FS) examinations in the management of patients undergoing thyroid
      surgery for unilateral thyroid nodules with benign or indeterminate cytology on
      preoperative fine-needle aspiration biopsies (FNABs). METHOD: A retrospective
      chart review of 190 consecutive patients with unilateral thyroid nodules
      undergoing thyroid surgery was undertaken between March 2006 and March 2008. The
      results of FNAB, FS, and final histology were obtained from the pathology report.
      A cost analysis was performed to compare the cost of routine FS examinations to
      determine malignancy with the cost of performing a second surgical procedure.
      RESULTS: Of the 169 patients evaluated, there were 53 cases of malignant nodules.
      Malignancy was diagnosed by FS in 16 of these 53 cases, resulting in a total
      thyroidectomy and thereby avoiding the need for a completion thyroidectomy. The
      sensitivity and specificity of FS examination were 30.2% and 100.0%,
      respectively. The routine use of intraoperative FS examination in cases of benign
      or indeterminate nodules afforded a total cost savings of $3719.27, or a cost
      savings of $22.01 per patient. CONCLUSION: FS examination was useful in guiding
      our intraoperative management for patients with unilateral thyroid nodules with
      benign or indeterminate preoperative FNAB. The routine use of FS was cost
      effective in our Canadian health care system, even without considering the
      intangible costs, such as patients' anxiety, emotional stress, and the loss of
      productivity owing to a second surgical procedure.

PMID- 19769827
TI  - Routine thyroidectomy in total laryngectomy: is it really indicated?
AB  - OBJECTIVE: To evaluate the incidence and nature of thyroid gland invasion (TGI)
      in laryngeal carcinoma at the head and neck centres at McGill University. METHOD:
      A retrospective case series was undertaken of 74 total laryngectomies performed
      at both McGill head and neck centres from 2001 to 2006. Thirteen specimens were
      excluded because thyroidectomies were not performed or laryngectomies were
      performed for nonprimary laryngeal carcinoma. Tumour stage, subsite, anatomic
      characteristics, and thyroid gland involvement were analyzed based on pathologic
      specimens. Pre- and postoperative radiation therapy treatment and thyroid
      function were also noted. RESULTS: Twenty supraglottic, 21 glottic, 15
      transglottic, and 5 subglottic tumours were analyzed. Subglottic extension > 10
      mm was noted in 22 specimens (36%). Cartilaginous invasion was noted in 37 of our
      specimens (61%), and lymph node metastasis was noted in 12 specimens (20%). One
      subglottic tumour demonstrated bilateral invasion of the thyroid gland and lymph
      node metastasis. Forty patients (54%) received preoperative radiation therapy and
      34 patients (46%) received postoperative radiation therapy, with pre- and
      postoperative rates of hypothyroidism of 38.9% and 91%, respectively. CONCLUSION:
      TGI is rare for laryngeal cancer. Tumours with subglottic involvement or very
      advanced tumours may show a greater tendency for TGI over other tumours.

PMID- 19769828
TI  - Perichondritis with or without external otitis and intradermal injection: a new
      therapeutic approach.
AB  - Auricular perichondritis and fiogosis of the external auditory canal are not
      uncommon pathology of the ear. These inflammatory processes are often accompanied
      by reactive locoregional lymphadenopathy. An inadequate or insufficient systemic
      therapy may lead to the persistence of otalgia and of signs of flogosis. The
      administration of local intradermaltherapy allows a strengthening of the
      pharmacological effect and a reduction in the quantity of drug used. It provides
      a rapid improvement in the locoregional signs of infection.Intradermal injection
      is performed on two pretragral points, two retroauricular points and one in the
      posterior surface of the pinna. The drugs injected are corticosteroids and
      antibiotics.The administration of intradermal therapy in the cases presented gave
      excellent results: control of pain, rapid improvement in the signs of infection,
      complete recovery from the flogosis, no side-effects.The intradermal lijection of
      small quantities of drugs allows a rapid and complete recovery from external
      otitis while the systemic approach leads often to the persistence of the
      flogosis.

PMID- 19769829
TI  - Prevalence of obstructive sleep disturbance in children with failure to thrive.
AB  - OBJECTIVES: Failure to thrive (FTT) is a serious condition of childhood, with
      failure to grow as expected for age and gender. Numerous potential etiologies
      have been suggested, including occult obstructive sleep disturbance (OSD). We
      determined the prevalence of OSD in an FTT population, examined correlation to
      tonsil size, and assessed correlation with a parental questionnaire regarding
      symptoms. PATIENTS AND METHODS: A cross-sectional prevalence study was conducted.
      Thirty-six FTT children in Boston Medical Center's FTT Clinic aged 12 to 60
      months were evaluated by formal polysomnography, parental questionnaire, and
      physical examination. The prevalence and nature of sleep disorders in this
      population are compared with published age-appropriate norms. RESULTS: The
      prevalence of OSD in an FTT population in these 36 children is 5.5%. This is
      compared with the prevalence in the general pediatric population, which is
      between 0.7 and 4.3%. CONCLUSIONS: The prevalence of OSD in FTT tends toward
      higher than published values for the general pediatric population but does not
      reach statistical significance. Tonsillectomy and adenoidectomy have been
      suggested in the literature to be of benefit to improve the growth of children
      with FTT. Sleep disturbance has been suggested as the underlying pathology.
      However, using current guidelines, we could not identify an increased prevalence
      of sleep disturbance in children with FTT. Nonetheless, a continued high level of
      clinical suspicion is necessary in appropriate diagnosis and treatment of OSD,
      found in some children with FTT. That growth in children with FTT often improves
      following management of sleep disturbance (eg, tonsillectomy) is not explained by
      a significantly higher incidence of OSD in this population.

PMID- 19769830
TI  - Comparison of ibuprofen and acetaminophen with codeine following cosmetic facial
      surgery.
AB  - OBJECTIVES: To compare the efficacy and side effects of ibuprofen and
      acetaminophen with codeine when given postoperatively following cosmetic facial
      surgery and to assess whether bruising is worse or the incidence of hematoma is
      greater when ibuprofen is taken postoperatively. DESIGN: Prospective, double
      blind, randomized trial. SETTING: Accredited outpatient surgery centre. METHODS:
      Study subjects received scheduled doses of either oral ibuprofen 400 mg or
      acetaminophen/codeine 600/60 mg four times a day through postoperative day 3.
      They recorded their pain level on a 10 cm visual analogue scale, as well as any
      untoward side effects, at scheduled times throughout the first 3 postoperative
      days. Severity of bruising was assessed on postoperative day 4. Any postoperative
      hematomas were managed and recorded. RESULTS: There was no significant difference
      in pain relief or average bruising scores between the two groups. Subjects
      receiving ibuprofen had significantly fewer adverse side effects and were less
      likely to change medications than those receiving acetaminophen with codeine.
      None of the patients in either group developed a postoperative hematoma.
      CONCLUSIONS: Ibuprofen 400 mg is as effective as acetaminophen/codeine 600/60 mg
      for pain relief following cosmetic facial surgery. Ibuprofen is better tolerated,
      with fewer side effects, than acetaminophen with codeine. Ibuprofen given
      postoperatively does not result in increased bruising or increased incidence of
      hematoma.

PMID- 19769831
TI  - Assessing flap perfusion: optical spectroscopy versus venous doppler
      ultrasonography.
AB  - OBJECTIVE: To use optical spectroscopy as a noninvasive method to monitor the
      viability of free flaps and to compare the near-infrared probe with the
      implantable venous Doppler ultrasound probe. DESIGN: Prospective, randomized
      series using an animal model. METHOD: Optical spectroscopy was used to measure
      variables that correlate with tissue perfusion and oxygenation. An epigastric
      artery island flap was raised in 20 rats. Vascular insults were simulated by
      clamping the vessels to the flap. Measurements were taken using near-infrared
      spectroscopy (NIRS) at the time of clamping and at 15, 30, 45, and 60 minutes of
      occlusion. The clamps were removed, and final NIRS measurements were taken. In
      the second experiment, a flap was raised in six rats, each of which underwent a
      series of short-lived occlusions. The occlusions were monitored with both NIRS
      and the implantable venous Doppler probe. RESULTS: In the first experiment,
      disruptions in flap perfusion resulted in significant changes in tissue
      hemoglobin oxygen saturation and total hemoglobin concentration as detected using
      NIRS. NIRS predicted vascular compromise with a sensitivity of 89.7% and a
      specificity of 97.9%. In the second experiment, NIRS predicted vascular
      compromise with a sensitivity of 63.3% and a specificity of 94.8%. The clinical
      assessment, based on recordings, yielded sensitivities and specificities of 70%
      and 94.8% (surgeon 1) and 71.7% and 94.8% (surgeon 2). CONCLUSION: Optical
      spectroscopy represents a reliable method of noninvasively monitoring free flaps.
      Further investigations as to the clinical utility of spectroscopy as an
      adjunctive monitoring device are currently being performed.

PMID- 19769832
TI  - The burden of psoriasis in Canada: insights from the pSoriasis Knowledge IN
      Canada (SKIN) survey.
AB  - BACKGROUND: Although some data addressing the burden of illness associated with
      psoriasis and psoriatic arthritis (PsA) have been reported for American and
      European patient populations, similar data have been lacking for Canadians with
      these diseases. OBJECTIVE: We sought to characterize the natural history of
      disease in a sample of Canadians with a history of moderate to severe psoriasis,
      with or without diagnosed PsA or other recognized comorbid conditions, and to
      identify factors that influenced their perception of psoriasis as a problem in
      their daily lives. METHODS: A nationwide telephone survey, pSoriasis Knowledge IN
      Canada (SKIN), was conducted between April 30 and June 2, 2007, on 500 people who
      indicated that they had been diagnosed with psoriasis and that their skin lesions
      had at some time affected an area at least as large as three palms of their hand
      (3% of body surface area [BSA]). RESULTS: The mean age at diagnosis for psoriasis
      among SKIN survey respondents was 28 years, with 31% (155 of 500) indicating that
      they developed the disease prior to age 18 years. At the time of the survey, 54%
      (269 of 500) of respondents were experiencing lesions affecting a BSA equivalent
      to at least three palms (3%). In response to questions on the burden of illness,
      35% (176 of 500) of respondents indicated that they considered psoriasis to be a
      substantial problem in their daily life. Both affected BSA at the time of the
      survey and self-reported extent of skin involvement at the height of the
      condition (BSAmax) correlated with the perception of psoriasis as a substantial
      problem. Other subpopulations in which psoriasis was commonly identified as a
      substantial problem included women and individuals with diagnosed PsA. Whereas
      18% (88 of 500) of respondents were diagnosed with PsA, the number who reported
      joint pain or stiffness was substantially higher (51%; 256 of 500), suggesting
      that some respondents may have had incipient or undiagnosed PsA. CONCLUSIONS:
      This survey reveals that psoriasis, PsA, and their associated comorbidities
      impose a severe burden on the daily lives of Canadians with a history of moderate
      to severe psoriasis.

PMID- 19769833
TI  - Ethyl chloride spray for sensory relief for botulinum toxin injections of the
      hands and feet.
AB  - BACKGROUND: Botulinum toxin injections are effective in the treatment of palmar
      and plantar hyperhidrosis, but discomfort has limited its use. OBJECTIVE: To
      study the use of ethyl chloride medium-stream spray in reducing injection
      discomfort. METHODS: We used ethyl chloride medium-stream spray, in conjunction
      with precooling by frozen ice packs, in our No Sweat Clinic for our most recent
      51 consecutive cases of botulinum toxin injection. RESULTS: Ethyl chloride spray
      greatly facilitated the injection procedure, and all patients completed the
      injections without hesitation or delay. CONCLUSION: Ethyl chloride medium-stream
      spray, in conjunction with precooling by frozen ice packs, is highly effective in
      reducing painful injection sensations. Its use is safe, economical, and easy to
      learn and does not require special equipment.

PMID- 19769834
TI  - Skin and soft tissue abscess: 1 year's experience.
AB  - BACKGROUND: The incidence of skin and soft tissue abscesses (SSTAs) has increased
      owing to the emergence of community-acquired methicillin-resistant Staphylococcus
      aureus (CA-MRSA). Some of these patients are treated as outpatients (OPs) and
      some as inpatients (IPs). OBJECTIVE: To review the microbiology and clinical
      features of SSTAs and the clinical parameters that may have influenced clinicians
      to treat patients as IPs. METHODS: The study was conducted in a 673-bed teaching
      hospital between January and December 2005. A retrospective chart review of
      patients identified from a microbiology culture log was conducted. Data were
      collected for demographics, underlying disease, SSTA number and site, recurrence
      rates, and clinical presentation. RESULTS: One hundred thirty-eight patients were
      identified; 76 (55%) were female, with a mean age of 42 years (range 18-80
      years); 76 (55.5%) had no underlying disease, 27 (19.6%) had diabetes, 20 (14.5%)
      had human immunodeficiency virus (HIV) infection, and 13 (9.4%) were intravenous
      drug users. Common SSTA sites involved were the perineal area (43; 31.2%), upper
      extremities (35; 25.4%), lower extremities (19; 13.8%), head and neck (14;
      10.1%), chest (13; 9.4%), and abdomen (8; 5.8%). CONCLUSIONS: CA-MRSA was the
      most commonly isolated organism overall and in patients treated as OPs. The
      decision to treat SSTA patients as IPs seems to be influenced by SSTA number and
      site and the presence of fever at presentation. SSTA number and site (variables
      that led to the decision to treat patients as IPs) were confirmed by
      demonstrating statistical significance in the analysis between the IP and OP
      groups, but the other determinant of admission, the presence of fever at
      presentation, was based on chart review statements and not confirmed by
      statistical analysis between the IP and OP groups.

PMID- 19769835
TI  - Ultraviolet light-induced leukoderma of the scalp associated with androgenetic
      alopecia: senescent actinic depigmentation of the scalp.
AB  - BACKGROUND: Human scalp skin is normally protected from sunlight and ultraviolet
      radiation by the presence of hair. When hair loss occurs, for example, in
      androgenetic alopecia, this protective factor declines. OBJECTIVE: We report a
      series of 10 type IV and V skin patients with a male predominance (60-85 years).
      All patients suffered from androgenetic alopecia starting from the age of around
      40 to 45 years. They all noticed asymptomatic, well-defined, depigmented macules,
      which were seen only in areas that have been afflicted by androgenetic alopecia.
      The depigmented macules remain within the confines of the hair margin. There has
      been no depigmented lesion elsewhere on the body. The patients did not report any
      association with any drug that they may have started taking. There is no history
      of vitiligo in these patients or their families. Biopsy samples taken from three
      of the patients showed solar elastosis. CONCLUSIONS: The entity of ultraviolet
      induced scalp leukoderma and androgenetic alopecia has not been acknowledged in
      dermatology textbooks but needs consideration for its importance in differential
      diagnoses. The term senescent actinic depigmentation of the scalp is suggested.

PMID- 19769836
TI  - Gnatophyma and otophyma.
AB  - BACKGROUND: Phymas are slowly progressive, disfiguring disorders of the face and
      ears that represent the end stage of rosacea. The most common phyma is
      rhinophyma, yet similar swellings may occur on the chin (gnatophyma), forehead
      (metophyma), one or both ears (otophyma), and eyelids (blepharophyma). OBJECTIVE:
      Unlike rhinophyma, otophyma is rarely seen. We report two rare phymas: a case of
      gnatophyma and a case of otophyma. METHODS: A 56-year-old African American man
      presented with a history of bumps on his chin that had begun about 7 years
      earlier. Physical examination was remarkable for lobulated plaques on the chin,
      coalescing into hypertrophic nodules and dilated pores. A 73-year-old African
      American male presented with bilateral cauliflower-like earlobe growths for the
      past 17 years. RESULTS: A skin biopsy was performed for each patient
      demonstrating cystic follicular dilatation with keratin plugging, dermal
      scarring, psoriasiform epidermal hyperplasia, and chronic inflammation of some of
      the follicles. CONCLUSION: This case report describes a relatively rare
      gnatophyma and otophyma. Surgical management is well accepted as the best mode of
      therapy to treat rhinophyma and is becoming a first-line treatment for all
      phymas.

PMID- 19769837
TI  - Cutaneous protothecosis following a tape-stripping injury.
AB  - BACKGROUND: Prototheca species are ubiquitous achlorophyllic algae that can, in
      rare instances, manifest as cutaneous infection in humans at sites of traumatic
      inoculation into the skin. OBJECTIVES: We report a 77-year-old man who developed
      cutaneous protothecosis at the site of an iatrogenic tape-stripping type injury.
      The diagnosis was confirmed by histologic examination and tissue culture. The
      patient responded completely to a 17-week course of oral fluconazole. CONCLUSION:
      Cutaneous protothecosis can present clinically as nonspecific indolent
      inflammatory plaques that require skin biopsy for definitive diagnosis.

PMID- 19769838
TI  - A wolf in sheep's disguise: rhabdomyosarcoma misdiagnosed as infantile
      hemangioma.
AB  - BACKGROUND: Rhabdomyosarcomas are a heterogeneous group of malignant tumors
      representing the most common soft tissue sarcoma of childhood. A delay in
      diagnosis is not uncommon. OBJECTIVE: To report a boy with paranasal
      rhabdomyosarcoma who was misdiagnosed and treated for infantile hemangioma.
      METHODS AND RESULTS: A 2-year-old Saudi boy who presented with a progressively
      increasing nasal mass for 18 months was misdiagnosed and treated for infantile
      hemangioma at an outside hospital. Histopathologic examination revealed paranasal
      rhabdomyosarcoma. CONCLUSION: We review some clinical clues that can alert the
      physician to malignant childhood tumors. We also review management options for
      childhood rhabdomyosarcoma.

PMID- 19769839
TI  - Utility of an interferon-gamma release assay for latent tuberculosis diagnosis in
      a case of bullous pemphigoid.
AB  - BACKGROUND: With increasing use of immunosuppressive therapy, including tumor
      necrosis factor alpha inhibitors, there is concern about infectious
      complications, including reactivation of latent Mycobacterium tuberculosis
      infection. Routine testing prior to administration of systemic immunosuppression
      includes the tuberculin skin test, which lacks sensitivity and specificity and
      may be difficult to interpret in the presence of extensive cutaneous disease.
      Treatment of individuals with latent tuberculosis infection is recommended when
      immunosuppressive medications are to be employed. OBSERVATIONS: We report a case
      in which a diagnosis of latent tuberculosis infection in a patient with extensive
      bullous pemphigoid was clarified by the use of an interferon-gamma release assay
      after equivocal tuberculin skin test results. CONCLUSION: Interferon-gamma
      release assays are useful adjuncts to the tuberculin skin test in the diagnosis
      of latent tuberculosis infection in the setting of extensive cutaneous disease.

PMID- 19769840
TI  - Allergy to extensively hydrolysed formulas.

PMID- 19769841
TI  - Hymenoptera venom allergy: characteristics, tolerance and efficacy of
      immunotherapy in the pediatric population.

PMID- 19769842
TI  - Hymenoptera venom allergy: characteristics, tolerance and efficacy of
      immunotherapy in the paediatric population.
AB  - Hymenoptera venom allergy is a growing problem in Spain. This problem has a
      special relevance in areas where population is frequently exposed to hymenoptera
      stings, being paediatric patients a high risk population. Immunotherapy with
      hymenoptera venom is an effective and safe treatment for these patients. However,
      there is a lack of data on the role of this treatment on paediatric population.
      For this reason, from the data base of the Allergy Unit from Hospital Xeral
      (Lugo, Spain) which includes 560 patients, have been analyzed the 21 paediatric
      patients, all of them treated with venom immunotherapy. Eighteen patients
      completed the treatment. The maintenance dose administered was 100 microg. Two
      systemic reactions (both with an Apis extract) were registered. Cutaneous test
      and specific IgE shown a statistical significant reduction at the end of
      treatment (p =.0004 and p <.0001 respectively). Seven patients (33 %) suffered a
      spontaneous re-stung during maintenance phase or after immunotherapy was
      completed. In 4 patients there was no allergic reaction and the other 3 children
      suffered a mild local reaction. In conclusion, venom immunotherapy is a safe and
      effective treatment in paediatric patients with hymenoptera venom allergy, being
      necessary to increase the experience on this specific segment of the allergic
      population.

PMID- 19769843
TI  - Socio-environmental conditions and geographical variability of asthma prevalence
      in Northeast Brazil.
AB  - BACKGROUND: This study aims to evaluate the association between environmental and
      socio-economic conditions with asthma prevalence in the eight ISAAC centres in
      North-East Brazil. METHODS: Estimates on occurrence, severity and medical
      diagnoses of asthma in the previous 12 months were compared using environmental
      and socioeconomic indicators. Associations were assessed using simple linear
      regression and Pearson correlation coefficient. RESULTS: There was no difference
      in asthma prevalence between centres. Active asthma prevalence increased with
      increasing water privation, and this would explain 62 % of the observed
      prevalence. Median temperature increase was inversely related to active asthma
      (r=0.81; p<0.05). There was a positive association between latitude and active
      asthma prevalence (r=0.82; p<0.005), a negative association between severe asthma
      and yearly medium temperature (r=-0.89; p<0.05), and a positive association with
      latitude (r=0.78; p<0.05). CONCLUSION: Relation between the tropical weather and
      high prevalence of asthma was not confirmed. There were associations with water
      privation and latitude.

PMID- 19769844
TI  - Triggers in adult asthma: are patients aware of triggers and doing right?
AB  - BACKGROUND: As triggers have a potential to induce asthma exacerbations,
      awareness of the patients to individual triggers as well as protective measures
      might be helpful to prevent asthma attacks. Though allergens and allergen
      avoidance have been studied extensively, there are only few studies on non
      allergic triggers and their avoidance for adult patients with asthma. In this
      study, we wanted to investigate asthma triggers and compliance to the preventive
      measures in an adult population. METHODS: One hundred and thirty one adult asthma
      patients were enrolled into the study. A face to face interview was done by using
      a questionnaire including individual asthma triggers, prevention measures against
      major modifiable triggers and knowledge sources of the cases. RESULTS: Regardless
      of asthma severity, 59.5 % of the subjects reported to be triggered by more than
      10 factors. The most common triggers were air pollutants (89.3 %) and weather
      changes (81.7 %). Severe group was more frequently affected by medications,
      emotional stress, weather changes and indoor pollutants than other severity
      groups (p=0.017, 0.014, 0.049 and 0.018, respectively) whereas stress was
      reported more frequently by females than males. Prevention measures were
      insufficient regarding some major triggers. CONCLUSION: Adult patients are
      vulnerable to several triggers regardless from underlying severity of the
      illness. Insufficient compliance to the major preventive measures indicates that
      new strategies are needed to prevent asthma attacks caused by modifiable
      triggers.

PMID- 19769845
TI  - Calculating the prevalence of atopy in children.
AB  - BACKGROUND: Atopy is an important risk factor for asthma, rhinitis, atopic eczema
      and urticaria. For this reason, several studies have been done to determine the
      prevalence of atopy in the paediatric population. The important differences among
      these studies do not allow the extrapolating of results. In this study, we
      calculate the prevalence of atopy and atopy-related diseases in a paediatric
      population using a different methodology. METHODS: Retrospective study among
      children referred for drug allergy in which the latter was discarded. We
      evaluated the prevalence of atopy (measured by allergen sensitisation), asthma,
      rhinitis, urticaria, atopic eczema and their characteristics. RESULTS: Three
      hundred and forty-two patients were studied for adverse drug reaction. This was
      discarded in 325/342 patients. 20 % of the children in the sample were atopic.
      Atopy prevalence increased with age. Some atopy related disease was observed in
      83/325 (25.5 %) children. Among these children allergen sensitisation increased
      from 42.3 % in the 0-3 years age group to 93.3 % in the 7-14 age group (p <
      0.0001). Prevalence of asthma was 11.5 %, 10.2 % and 7 % in the 0-3, 4-6 and 7-14
      age groups, respectively. Prevalence of rhinoconjunctivitis increased through age
      groups with a prevalence of 20 % among the 7 to 14-year old children. CONCLUSION:
      The use of this type of methodology seems to be correct to estimate the
      prevalence of atopy. Prevalence of allergen sensitisation is very high among 7 to
      14-year old children with asthma and/or rhinoconjunctivitis.

PMID- 19769846
TI  - Risk factors and prevalence of asthma in schoolchildren in Castellon (Spain): a
      cross-sectional study.
AB  - BACKGROUND: Research on potential risk factors of asthma can enhance our
      understanding of geographic differences and inform decisions on preventive
      strategies. METHODS: In 2002, a cross-sectional population-based study was
      carried out in the area of Castellon (Spain), following the International Study
      of Asthma and Allergies in Childhood (ISAAC) Phase III methodology. Asthma
      symptoms and related risk factor questionnaires were completed by parents of 6-7
      year-old schoolchildren. Logistic regression was used in the analysis. RESULTS:
      Participation rate was 88 % (4492 of 4872 schoolchildren). Prevalence of wheeze
      in the past year, asthma ever, and physician-diagnosed asthma were 8 %, 7 % and 6
      %, respectively. Risk factors independently associated with all three asthma case
      definitions were history of bronchitis or pneumonia, allergic rhinitis, family
      members with atopic disease, and residing in an industrialised area. Risk factors
      for asthma ever and physician-diagnosed asthma were male sex, atopic eczema and
      presence of a dog at home; exclusive breast-feeding and the presence of another
      animal (not a dog or cat) were protective factors. Maternal age was inversely
      related to physician-diagnosed asthma. Residence in an area of heavy truck
      traffic and the father smoking at home were associated with asthma ever. Risk
      factors for wheeze in the past year were low social class, history of sinusitis
      and the father smoking at home. CONCLUSIONS: Environmental factors are related to
      the presence of asthma. Preventive measures should be directed to improving air
      pollution, promoting breast-feeding and reducing smoking in the home.

PMID- 19769847
TI  - Immunotherapy in the treatment of food allergy. Does it have a future?

PMID- 19769849
TI  - Skin prick tests and allergy diagnosis.
AB  - Skin testing remains an essential diagnostic tool in modern allergy practice. A
      significant variability has been reported regarding technical procedures,
      interpretation of results and documentation. This review has the aim of
      consolidating methodological recommendations through a critical analysis on past
      and recent data. This will allow a better understanding on skin prick test (SPT)
      history; technique; (contra-) indications; interpretation of results; diagnostic
      pitfalls; adverse reactions; and variability factors.

PMID- 19769848
TI  - How to apply for research grants in allergology.
AB  - This is a guide for grant application for researchers seeking research grants in
      the field of allergy and related diseases for the first time. It outlines how to
      organize proposals and the potential issues to be considered in order to fulfil
      the criteria of the funding bodies and thus improve chances of obtaining the
      desired funding when applying for a research grant. We will use this paper as an
      example of a grant proposal to be presented to the FIS "Fondo de Investigacion
      Sanitaria" (Health Research Fund) of Spain. The general framework can be used for
      a research proposal to any funding agency. The main research designs are
      reviewed. Other topics such as hypothesis, objectives, methodology, ethics and
      legal issues, and budget are presented.

PMID- 19769850
TI  - Imported subclinical house dust mite sensitisation in migrants from geohelminth
      endemic developing countries.

PMID- 19769851
TI  - Ambroxol-induced systemic contact dermatitis confirmed by positive patch test.

PMID- 19769852
TI  - Severe allergy to poultry meat without sensitisation to egg proteins with
      concomitant Leguminosae allergy. Case report.

PMID- 19769853
TI  - Allergic rhinitis and childhood sleep disordered breathing.

PMID- 19769855
TI  - [Deleterious effects of stable nitric oxide derivatives, a uveitis inflammatory
      marker, on cultured bovine ocular layers].
AB  - INTRODUCTION: Uveitis is an intraocular inflammation affecting various eye
      segments. This disease is characterized by a high level of nitric oxide
      production. It is estimated via the quantification of its end products: nitrites
      and nitrates. In a previous study, we showed the cytotoxic effect of these
      molecules on bovine retina in vitro. In this study, we investigated the effect of
      these two molecules on cultured ocular explants in vitro. METHODS: After clinical
      examination, healthy bovine eyes were obtained immediately after enucleation and
      were transported to the laboratory at +4 degrees C. After dissection, ocular
      explants from anterior and posterior segments were cultured in DMEM supplemented
      with 10% of FBS, 2mM glutamine, 100UI penicillin, and 100UI/ml streptomycin.
      Cultures were treated with either nitrites or nitrates at different
      concentrations (300-500 microM). After culture incubation (24-48h), ocular
      explants were fixed in buffered formalin and the histological study was
      performed. RESULTS: All structures showed structural alterations in relation with
      culture duration and molecule concentrations. The different structures showed
      different degrees of sensitivity depending on the type and concentration of the
      metabolite used. Sclerotic analysis showed very little response to the two
      molecules, whereas the cornea and ciliary process epithelia showed the highest
      sensitivity. CONCLUSION: Our results showed a cytotoxic effect of nitrites and
      nitrates on ocular structures in vitro. This effect was correlated with molecule
      concentration and duration of exposure. The structural alterations observed
      suggest that nitric oxide, via its products, is implicated in the ocular lesions
      observed during uveitis.

PMID- 19769856
TI  - [Corneal allograft rejection after Descemet stripping automated endothelial
      keratoplasty (DSAEK): report of three cases].
AB  - INTRODUCTION: Descemet stripping automated endothelial keratoplasty (DSAEK) is an
      exciting alternative to standard full-thickness penetrating keratoplasty (PK) for
      the treatment of patients suffering from endothelial failure of the cornea.
      Corneal transplant rejection is the leading cause of endothelial failure after
      PK. While DSAEK may reduce the risk of corneal allograft rejection, endothelial
      rejection can still occur. CASE REPORTS: We report three cases of endothelial
      rejection after DSAEK. Subacute endothelial rejection occurred in all three cases
      after the topical steroid treatment regimen had been stopped. CONCLUSION: A lower
      rejection rate in comparison with PK cannot be assumed and comparative studies
      are necessary. Extended topical steroid may be used. Subacute endothelial graft
      rejection implies that the patient needs to be fully informed of the functional
      signs and the need to seek medical advice immediately.

PMID- 19769857
TI  - [Study of optic nerve head-fovea angle with retinophotography in congenital
      fourth nerve palsy].
AB  - PURPOSE: Measurement of ocular torsion is an important element for analysis of
      certain oculomotor pathologies such as fourth nerve palsy. With nonmydriatic
      retinography, objective measurements of ocular torsion are now accessible in
      daily practice: the normal values in healthy subjects are known. We compared a
      population of subjects with fourth nerve palsy to a reference population.
      PATIENTS AND METHODS: Prospective study of 38 cases of congenital fourth nerve
      palsy, who had never undergone surgery. Each of these subjects had nonmydriatic
      retinography done according to a standardized protocol. The ocular torsion was
      measured using graphic software with consideration of reproducible anatomical
      marks. A statistical study determined the thresholds of significance. RESULTS: In
      this pathological population, the angle between the optic nerve head and fovea is
      organized in a Gaussian distribution but the values are different from those
      found with the same method in a population of healthy subjects (6.3 degrees +/
      3.4) (t test, p<0.0001). Extorsion exists in paralytic eyes (mean, 10.7 degrees
      +/-3.8), as in the other eye (mean, 8.8 degrees +/-5.7). In addition, the study
      of the anatomical marks of the fundus (optic nerve head and the lower pole of the
      papilla) was shown to be reliable. DISCUSSION: This study confirms ocular
      torsion's variation in fourth nerve palsy. Extortion was found in both eyes. We
      demonstrated no relation between the severity of the extortion and the
      lateralization of the fixating eye. We confirmed the results of previous studies.
      CONCLUSION: This study confirms the relevance of the objective measures of the
      ocular torsion in a pathological situation. Simple anatomical marks of eye fundus
      provide a useful analysis of these clinical presentations.

PMID- 19769858
TI  - [25-Gauge transconjunctival vitrectomy in a case of bilateral epiretinal membrane
      associated with a Terson syndrome].
AB  - The formation of epiretinal membranes associated with proliferative
      vitreoretinopathy is known to be a complication of Terson syndrome. We report the
      first case of a 25-Gauge transconjunctival sutureless vitrectomy performed in one
      eye as treatment for an epiretinal membrane secondary to a case of Terson
      syndrome (most probably due to a history of subdural hematoma in childhood).
      Following a review of the current literature on the subject we report the
      physiopathologic mechanisms of Terson syndrome and the explanation for the
      proliferative vitreoretinopathy formation.

PMID- 19769859
TI  - [Ocular lesions after bee sting of the cornea. A case report].
AB  - Bee stings of the cornea are rarely reported but can potentially cause serious
      ophthalmologic injuries. Locally, damage occurs through toxic and immunologic
      reactions and from the stinger retained in the cornea. Early recognition of the
      possible complications and appropriate treatment may help to prevent permanent
      loss of vision. Removal of a retained bee stinger remains controversial. We
      present a case of corneal bee sting with retained stinger apparatus and
      associated anterior uveitis and discuss the pathologic mechanisms of injury and
      evaluation of these uncommon presentations.

PMID- 19769860
TI  - [Endogenous Klebsiella pneumoniae endophthalmitis secondary to a renal abscess: a
      case report].
AB  - We report the case of an 86-year-old man with unilateral panuveitis concurrent
      with an infectious retinal focus. The diagnosis of endogenous endophthalmitis
      with subretinal abscess was suggested. The biology workup and CT scan showed a
      renal abscess. This was caused by Klebsiella pneumoniae, which was confirmed by
      analysis of abscess aspiration and vitrectomy samples. This paper underscores the
      importance of etiological assessment in infectious panuveitis and the
      consequences on visual outcome.

PMID- 19769861
TI  - [Macular edema revealing scleral necrosis following scleral buckling surgery].
AB  - INTRODUCTION: Macular edema is a very rare complication of scleral necrosis after
      scleral buckling surgery. OBSERVATION: We report the case of a 45-year-old women
      with an ocular history of severe myopia in both eyes and retinal detachment in
      the left eye. She underwent segmental scleral buckling in 2003. Two years and
      nine months later, the patient had acute, painless visual loss in her left eye.
      Funduscopic examination revealed cystoid macular edema with no intraocular
      inflammation. A fluorescein angiography and OCT revealing cystoid macular edema
      consistent with the macular edema was noted clinically. The surgical exploration
      revealed scleral necrosis beneath the scleral buckle. After removal of the
      scleral buckle, a scleral patch was performed. Several months after surgery, the
      vision had improved; funduscopic examination and OCT revealed no residual macular
      thickening. DISCUSSION: Macular edema is a rare complication of scleral necrosis
      following scleral buckling surgery, with only one case described in the
      literature. Our patient's complication occurred 2 years after surgery. The
      macular edema is likely the result of the scleritis. This inflammatory process
      can extend from the sclera and result in several ocular complications, including
      uveitis. Regression of macular edema occurs frequently after removal of the
      scleral buckle.

PMID- 19769862
TI  - [Aspect of necrosis preceding macular hole from laser accident].
AB  - We report the clinical case of a 26-year-old victim of a macular injury by high
      energy laser. The patient was examined in the emergency unit the first day with a
      retinophotography. He was followed up at 1 week, 3 weeks, and 3 months with an
      ophthalmologic exam, a retinophotography, and an OCT. The lesions progressed from
      edema with macular hemorrhage to macular necrosis and then to a macular hole. The
      macular injury by high energy laser was responsible for a necrotic modification
      of the macula preceding the formation of the macular hole.

PMID- 19769863
TI  - [Recommendations for carrying out intravitreal injections].

PMID- 19769864
TI  - [An update on the use of tissue adhesives in ophthalmology].
AB  - Tissue adhesives have a long history of use in almost all surgical disciplines,
      both as an alternative and a complement to sutures. Nevertheless,
      ophthalmologists have restricted knowledge of their potential applications;
      consequently, tissue adhesives have been underutilized so far. This review
      discusses the most relevant clinical and experimental advances in the use of
      tissue adhesives in ophthalmology and details the characteristics and properties
      of the glues. Among the currently available adhesives, synthetic glues are mainly
      represented by cyanoacrylates and biologic glues by fibrin-based adhesives.
      Cyanoacrylate-based glues are especially useful for treating perforated or
      preperforated corneal ulcers and performing temporary tarsorrhaphy. Fibrin-based
      glues have the largest field of application, as they can be used in corneal
      perforations and are being widely used in pterygium surgery and conjunctival
      surgery. We also reviewed other anecdotic applications of these adhesives. Novel
      biomaterials such as biodendrimers, polyethylene glycols, modified chondroitin
      sulfates, and acrylic copolymers show promising results in the experimental
      field, and one product has been on the market for a short period of time.

PMID- 19769865
TI  - [Peters' syndrome: biomicroscopic, echographic and Scheimpflug examination].

PMID- 19769866
TI  - [Subretinal hemorrhage after intravitreal injection of anti-VEGF for age-related
      macular degeneration: a retrospective study].
AB  - INTRODUCTION: Prescription of anti-VEGF treatments have increased substantially
      over the past few years in treatment of wet age-related macular degeneration. We
      report the occurrence of macular hemorrhages after one year of use of anti-VEGF
      intravitreal injections, mainly for subfoveal choroidal neovascularization.
      MATERIAL AND METHODS: Four hundred forty five injections were given over one year
      (from 15 March 2007 to 15 March 2008), for age-related macular degeneration,
      retinal vascular occlusion, diabetic retinopathy, neovascular glaucoma, and
      idiopathic macular choroidal neovascularization; distributed as follows: 11.5%
      Bevacizumab, 18.6% Pegaptanib, 19.3% Triamcinolone, and 50.6% Ranibizumab.
      RESULTS: Six macular hemorrhages were observed, resulting in to a sharp decrease
      in visual acuity (20/400), with loss of five lines. All occurred after one
      injection of nonselective anti-VEGF (Ranibizumab) on already treated eyes (four
      previous injections on average, +/- photodynamic therapy). All were secondary to
      occult choroidal neovascularization or a large pigment epithelial detachment.
      Three patients presented a pigment epithelial tear. DISCUSSION: Anti-VEGF
      intravitreal injections can lead to pigment epithelial tears in case of large
      pigment epithelial detachment, especially with a small feeder vessel or with
      large occult choroidal neovascularization. The authors discuss the possible
      implications of anti-VEGF when macular hematoma occurs: retraction of choroidal
      neovascularization and alteration of physiological retinal vascularization.
      CONCLUSION: Macular hematoma affects visual prognosis in age-related macular
      degeneration. It may follow intravitreal anti-VEGF injection with large occult
      neovascularization, especially in previously treated eyes. Injection in large
      pigment epithelial detachment may cause a risk of epithelial tear. Other studies
      are necessary to evaluate the role of the nonselective anti-VEGF in the incidence
      of macular hematoma.

PMID- 19769867
TI  - [Macular edema without fluorescein leakeage].
AB  - PURPOSE: To study the OCT (optical coherence tomography) features of cases of
      unexplained macular edema, which were not combined with fluorescein leakage on
      angiography. PATIENTS AND METHOD: We report a retrospective series of three
      patients who presented with visual acuity impairment due to unilateral macular
      thickening visible on OCT examination. All eyes studied underwent OCT and
      angiography and electrophysiological examinations. None of the patients had a
      medical record and none of the eyes studied was highly myopic. RESULTS: OCT
      profiles shared characteristics of myopic foveoschisis or X-linked retinoschisis.
      No fluorescein leakage was detected on angiography. The electrooculogram was
      impaired in one eye while other electrophysiological investigations were normal
      in all eyes. DISCUSSION: Most frequently, macular edemas are associated with a
      fluorescein leakage on angiography. Macular edemas without angiographic leakage
      may correspond to unilateral idiopathic retinoschisis or macular edemas, with an
      atypical mechanism of intraretinal fluid accumulation.

PMID- 19769868
TI  - [Artificial iris intraocular lenses in aniridia or iris deficiencies].
AB  - PURPOSE: To study artificial iris intraocular lens (IOL) or ring specially
      designed for correction of aniridia or iris deficiencies associated with cataract
      or aphakia. PATIENTS AND METHOD: Nine patients with partial or total aniridia
      underwent the surgical procedure. A black (Morcher 67F) or brown (Ophtec 311)
      diaphragm intraocular lens was used for the seven patients with aphakia. Morcher
      50C rings were used for the patients with cataract. RESULTS: The esthetic results
      were satisfactory. Photophobia was reduced in all cases. Postoperative
      complications included one case of transient hypertony and one case of retinal
      detachment. CONCLUSION: We recommend the use of artificial iris IOL or rings in
      aniridia associated with cataract or aphakia.

PMID- 19769869
TI  - [Contribution of GDx-VCC in ocular hypertensive patients: a complement to blue-on
      yellow perimetry and FDT matrix?].
AB  - INTRODUCTION: Evaluate the importance of GDx-VCC results compared with FDT Matrix
      and blue-on-yellow perimetry in a population of ocular hypertensive patients.
      METHODS: Prospective study including 135 eyes of 135 patients. All had normal
      standard achromatic perimetry and intraocular pressure greater than 21 mmHg
      without medication. They underwent short wavelength automated perimetry (SWAP) 24
      2 FASTPAC, FDT Matrix 24-2 Threshold strategy, and retinal nerve fiber layer
      (RNFL) analysis with GDx-VCC. RESULTS: Fifty two patients had neither structural
      (GDx-VCC) nor functional (SWAP and Matrix) optic nerve injury. Eighty-three
      patients had preperimetric glaucoma (at least one of the tests showed pathologic
      results). We found isolated functional defects (38% cases), isolated structural
      lesions (31% cases), or mixed injury (31% cases). When GDx-VCC revealed
      structural damage, Matrix was abnormal in 30%, as was SWAP in 8% of cases. Both
      functional and structural evaluation revealed identical defects for 12% of
      patients. RNFL loss could be either diffused or compatible with typical
      glaucomatous topography. Most temporal damage was detected by FDT Matrix, whereas
      SWAP performed better for nasal defects. The results of GDx analyses correlated
      better with Matrix than with SWAP. CONCLUSION: When associated with automated
      perimetry, GDx-VCC is a valuable tool to evaluate optic nerve damage and detect
      preperimetric glaucoma. Clinical evaluation of the optic nerve head remains
      essential. We found a good correlation between visual field defects and
      structural injuries.

PMID- 19769870
TI  - [Congenital glaucoma: future of vision and pressure. Results of an 11-year
      study].
AB  - AIM: To study the future of vision and IOP in congenital glaucoma. MATERIAL AND
      METHODS: We studied 33 eyes from 20 separate patients divided into two groups:
      group one consisted of 19 eyes with isolated trabeculodysgenesis and group two 14
      eyes associated with Sturge-Weber-Krabbe syndrome, angiomatosis, or Peters
      syndrome. All patients underwent filtering surgery between 1995 and 2006. We
      studied a number of different forms of surgery; visual acuity after amblyopia
      treatment (> or =5/10, good; 4/10-2/10, average; < or =1/10, poor), objective
      refraction, and intraocular pressure (<16 mmHg, good; > or =16 mmHg, poor).
      RESULTS: We found that 54.8% of the patients had visual acuity 5/10 or greater
      and 44.2% between 4 and the ability to perceive light. Objective refraction was
      emmetropic in 19.4% (group 1, 60%; group 2, 40%), myopic in 53.8% (group 1,
      28.5%; group 2, 71%), and hyperopic in 26.9% of cases (100%, group 1). All
      patients underwent surgery (45.5% deep sclerectomy and 54.5% trabeculectomy);
      39.4% of the patients underwent more than one type of surgery (the number of
      operations is a prognosis factor for visual acuity). IOP was less than 19 mmHg in
      87.9% of eyes. DISCUSSION: Visual acuity, refractive errors, and IOP depend on
      the type of congenital glaucoma. Isolated trabeculodysgenesis seems to give a
      better prognosis. CONCLUSION: If early diagnosis and treatment occur, visual
      acuity that is 5/10 or less can be expected for more than 50% of patients;
      therefore their visual future seems to be better.

PMID- 19769871
TI  - [Traumatic peri-ocular injuries: closing wounds using 2-octyl-cyanoacrylate
      medical glue].
AB  - INTRODUCTION: Periocular injuries are a common reason for emergency ophthalmology
      consultations. Their treatment raises specific problems related to skin
      sensitivity and mobility as well as the ocular safety of the procedure, notably
      in children. The properties and method of use of synthetic adhesive Dermabond
      adhesive make it a useful tool for the treatment of these injuries. However, no
      study to date has evaluated this tool in terms of its efficacy, safety, and
      esthetic results. PATIENTS AND METHOD: This prospective study included all
      patients presenting with linear, superficial, or deep wounds to the eyelid and/or
      eyebrows, consulting an emergency department over a 3-month period. It comprised
      the clinical and photographic follow-up of each patient. Of these patients, those
      receiving treatment with synthetic adhesive were selected on the basis of
      specific criteria. RESULTS: The study population comprised seven patients (four
      of them children) presenting with six wounds to the eyelid, and two to the
      eyebrow. This adhesive was applied to four patients. Their mean follow-up was 22
      days. No events threatening their safety were reported while using this adhesive,
      particularly in the children. Its immediate efficacy and comfort for the patient
      were deemed highly satisfactory. The esthetic outcome after 1 month could not be
      assessed. CONCLUSION: Use of Dermabond synthetic adhesive is an effective,
      practical, and safe technique for the treatment of wounds to the eyelid and
      eyebrows. It was particularly appreciated in children.

PMID- 19769872
TI  - [Severe disseminated toxoplasmosis with atypical chorioretinitis. A case of
      primary infection].
AB  - The clinical diagnosis of ocular toxoplasmosis is based on clinical features and
      biological tests: polymerase chain reaction (PCR) and the determination of
      intraocular specific antibody secretion (Goldmann-Witmer coefficient) on aqueous
      humor. Older patients may have a higher prevalence of ocular involvement and more
      severe ocular disease during the acute phase of recently acquired systemic
      infection because of altered cell-mediated immunity. Moreover, the genotype of
      the infecting parasite (particularly involving neotropical Type I Toxoplasma
      gondii strain), appears to be an important determinant of disease severity.

PMID- 19769873
TI  - [Subconjunctival dirofilariasis: a case report].
AB  - INTRODUCTION: Dirofilariasis is a disease rarely seen in humans, occurring
      commonly in noncarnivorous mammals. The microfilariae are transmitted by a
      mosquito vector. Ocular dirofilariasis is rarely described in the ophthalmic
      literature. CASE REPORT: An 81-year-old woman living in the north of France had a
      history of sudden pain and swelling of the left orbit. On slit lamp examination,
      a white worm was seen under the superior bulbar conjunctiva. Excision of the
      subconjunctival worm was adequate treatment and was important for parasite
      identification. DISCUSSION: Dirofilariasis is broad-based and is more common in
      Italy. Cases in France are found in the south. Ocular symptoms are frequently
      subconjunctival, but many cases of orbital involvement are found. Treatment is
      only surgical; systemic medication is not necessary. CONCLUSION: Ocular
      dirofilariasis is exceptional. Case reports in ophthalmic literature are rare.
      This parasite infection is probably underdiagnosed.

PMID- 19769874
TI  - [Neonatal pathologies of the lacrimal system].
AB  - Neonatal obstruction of the distal part of the lachrymal system can lead to
      dilatation of the lachrymal sac if associated with a canaliculus problem.
      Clinical presentation is a blue tumor of the internal canthus. This external
      expansion of the lachrymal sac communicates with a nasal expansion under the
      inferior nasal turbinate. Even if this typical presentation is spectacular,
      spontaneous resolution occurs in 80% of cases. There are two main types of
      progression: an abscess of the lachrymal sac can occur (20%) or bilateral nasal
      respiratory obstruction in cases of bilateral obstacle because newborns are
      obligatory nose breathers (<0.1%).

PMID- 19769875
TI  - [Orbital tumor emergencies in childhood].
AB  - Emergencies in childhood orbital tumorals are rare. The absolute emergency
      involves malignant primary orbital tumors, such as rhabdomyosarcoma or secondary
      malignant tumors (metastatic neuroblastoma, leukemia), involving a vital
      prognosis requiring prompt diagnosis. Delayed emergencies are usually vascular
      lesions. Among these lesions, immature orbital hemangioma, with a good prognosis,
      must be distinguished from orbital adnexal lymphangiomas, which are less frequent
      but can lead to dramatic cosmetic and functional disorders. In rare cases, they
      can be responsible for sudden, painful proptosis, due to orbital hemorrhage, with
      a risk of optic nerve compression, requiring emergency surgical treatment.
      Neurogenous lesions, either isolated, such as in gliomas, or associated with a
      systemic disease, such as Recklinghausen neurofibromatosis, threaten the
      functional prognosis. Diagnosis of pediatric orbital tumors is based on a good
      clinical examination, precise imaging investigations, and evaluation of the
      locoregional extension of the tumor. Biopsy is required in emergency situations,
      when rhabdomyosarcoma is suspected, in order to start the chemotherapy. However,
      the biopsy can be superfluous, and even useless or dangerous, when clinical and
      imaging investigations are sufficient to provide a diagnosis of capillary
      hemangioma, lymphangioma, or metastatic tumor from an abdominal malignancy.
      Treatment is closely related to the etiopathogenesis of the tumor. The outcomes
      are vital, functional and cosmetic. They may require orbital surgery (biopsy,
      tumoral resection, orbital decompression in case of a compressive hemorrhage),
      systemic corticotherapy (as in immature adnexal hemangioma), radiation, and
      chemotherapy (rhabdomyosarcoma, secondary malignant tumor). These diseases
      require a pediatric ophthalmological medical center specializing in orbital
      surgery, with close collaboration of multiple specialists such as onco
      pediatricians and neurosurgeons.

PMID- 19769876
TI  - [Orbital infections in children: clinical signs, imaging, and treatment].
AB  - Orbital infections are rare in children. The more posterior the abscess has
      spread, the more serious it is, with potential intracranial complications. The
      main etiology is sinusitis, whose location depends on age. The diagnosis is based
      on clinical examination and CT or MRI. Intravenous antibiotics alone or
      associated with surgical drainage (for children older than 9 years or those with
      complications) are performed. Orbital infections in children require good
      collaboration between ophthalmologists, otolaryngologist, and pediatricians.

PMID- 19769877
TI  - [Palpebral and lacrimal system injuries in children].
AB  - The authors report the different palpebral and lacrimal wounds found in children
      and their treatment. Early microscopic surgery is important for good prognosis.
      The eyelids must be thoroughly examined searching for a marginal injury, superior
      palpebral levator muscle resection, and lacrimal system injury after ocular
      injuries have been investigated. The treatment is microscopic surgery of the
      eyelid and the canaliculus with most often a monocanalicular intubation. The
      authors present two clinical studies conducted in the Reims Hospital that show
      the frequency of this traumatology and the main characteristics. In children,
      most injuries come from dog bites with canalicular laceration in the left lower
      eyelid. In palpebral injuries without canalicular section, the injury was most
      often located on the right lower eyelid. Preliminary treatment of childhood
      palpebral and lacrimal injuries is necessary with microscopic surgery. It is
      important to repair the canaliculus with or without canalicular intubation and
      the eyelid margin.

PMID- 19769878
TI  - [Visual acuity loss in young patient and cutaneous lesions: pseudoxanthoma
      elasticum].

PMID- 19769879
TI  - [Abstracts of the 26th Congress of the SFE (French Society of Endocrinology),
      October 2009, Nice, France].

PMID- 19769880
TI  - Antiplatelet agents used for early intervention in acute coronary syndrome:
      myocardial salvage versus bleeding complications.

PMID- 19769881
TI  - Long-term results of aortic valve-sparing operations in patients with Marfan
      syndrome.
AB  - OBJECTIVE: The appropriateness of aortic valve-sparing operations in patients
      with Marfan syndrome has been questioned. This study examines the long-term
      results of these operations in patients with Marfan syndrome. METHODS: From 1988
      to 2006, 103 consecutive patients with Marfan syndrome (mean age, 37 +/- 12
      years) and aortic root aneurysm had aortic valve-sparing operations. Emergency
      surgery was performed in 11 patients: 8 for acute type A aortic dissection and 3
      for unexplained persistent chest pain. Fourteen patients also had mitral valve
      surgery. The technique of aortic valve reimplantation was used in 77 patients,
      and aortic root remodeling was used in 26 patients. Patients were followed
      prospectively and underwent annual echocardiographic studies. The mean follow-up
      was 7.3 +/- 4.2 years and 100% complete. RESULTS: There was 1 operative death and
      5 late deaths. Four of the 6 deaths were due to complications of aortic
      dissections. The patients' survival at 15 years was 87.2% compared with 95.6% for
      the general population of Ontario matched for age and sex. Seven patients had
      important aortic insufficiency: 4 mild to moderate, 2 moderate, and 1 moderate to
      severe. Freedom from greater than mild aortic insufficiency at 15 years was
      79.2%. Three patients, all after aortic root remodeling, had aortic valve
      replacement, 2 for aortic insufficiency and 1 for endocarditis. At the most
      recent follow-up, 97 patients were alive: 86 were in functional class I, and 11
      were in functional class II. CONCLUSIONS: Aortic valve-sparing operations
      provided excellent clinical outcomes in this series of patients with Marfan
      syndrome. Postoperatively, complications of aortic dissections were the leading
      cause of death.

PMID- 19769883
TI  - Minimally invasive operation for congenital heart disease: a sex-differentiated
      approach.
AB  - OBJECTIVES: Since 1996, we have routinely used a minimally invasive sex
      differentiated surgical approach for surgical repair of various simple congenital
      heart diseases, mostly including a right anterior minithoracotomy in female
      subjects and a midline ministernotomy in male subjects. METHODS: Between August
      1996 and December 2004, all patients who underwent a sex-differentiated surgical
      approach were included. Hospital results were compared with those of a group
      undergoing full sternotomy (control subjects). Patients' clinical conditions and
      satisfaction at follow-up were evaluated. RESULTS: Three hundred eight patients
      underwent the sex-differentiated surgical approach: (1) minithoracotomy in 147
      (47.7%) and (2) ministernotomy in 161 (52.3%). Thirty patients had a full
      sternotomy for atrial septal defect closure. The most common diagnosis was an
      atrial septal defect (231 [75%] patients). None of the patients required an
      extension of the surgical access. There were neither major complications nor
      hospital deaths. All patients were discharged home without residual defects.
      Median follow-up time was 71.5 months (range, 48.2-85.7 months). There were no
      late deaths. No scoliosis, asymmetric breast development, or lactation problems
      were reported in the minithoracotomy group. Twenty-five (17%) of 147 patients
      with minithoracotomies complained of a trivial, persistent (<6 months), sensitive
      skin deficit in the mammary area, most often localized at the inferomedial
      quadrant. The vast majority of patients (296 [96%] 308 patients) were in New York
      Heart Association class I, and 282 (91.5%) of 308 patients were satisfied with
      the cosmetic result of the operation. CONCLUSIONS: The sex-differentiated
      surgical approach for simple congenital heart disease is a safe procedure,
      providing both excellent functional and cosmetic results. Anterolateral
      minithoracotomy is a valid and highly appreciated procedure in female patients.

PMID- 19769884
TI  - Layered implantation of myoblast sheets attenuates adverse cardiac remodeling of
      the infarcted heart.
AB  - OBJECTIVE: We previously showed that autologous myoblast sheets constructed with
      tissue-engineering techniques improved the function of the impaired heart. In
      this study, we evaluated the effects of layered myoblast sheets to clarify
      whether increasing the number of sheets provides improvement of cardiac function.
      METHODS: Myoblast sheets were constructed in dishes that release confluent cells
      from the dish surface via temperature reduction. Sixty infarcted Lewis rats
      underwent implantation of myoblast sheets on the infarcted area. There were 4
      groups (n = 15 in each group): S1: one layer, S3: three layers, S5: five layers,
      and a sham group. We examined cardiac function by echocardiography and
      catheterization, mRNA expression by real time reverse-transcriptase polymerase
      chain reaction, and histology. RESULTS: The ejection fraction and end-systolic
      pressure-volume relationship in the S5 and S3 groups were significantly improved.
      End-diastolic area was significantly reduced in the S5 group. The mRNAs for
      hepatocyte growth factor, vascular endothelial growth factor, and stromal cell
      derived factor-1 were all up-regulated in dose-dependent fashion. On histologic
      examination, fibrosis was most decreased in S5, and vascular density was
      increased. Cellular hypertrophy was attenuated in both the S5 and S3 groups.
      Elastic fibers were massively up-regulated in the infarction and implanted sheets
      in the S5 and S3 groups, with expression of the elastin gene. CONCLUSIONS:
      Implantation of three- and five-layered myoblast sheets yields favorable results,
      with better improvement of cardiac function, induction of angiogenesis, more
      elastic fibers, and less fibrosis. Thus, layered myoblast sheets, in optimal
      numbers, may attenuate adverse cardiac remodeling of the infarcted heart.

PMID- 19769885
TI  - Acute hepatitis C virus and the cardiac surgeon: an explanation needed.

PMID- 19769887
TI  - Latest information for the thoracic surgeon from the Annual Meeting of the
      American Society of Clinical Oncology.

PMID- 19769888
TI  - Joint policy statement--guidelines for care of children in the emergency
      department.
AB  - Children who require emergency care have unique needs, especially when
      emergencies are serious or life threatening. The majority of ill and injured
      children are brought to community hospital emergency departments (EDs) by virtue
      of their geography within communities. Similarly, emergency medical services
      (EMS) agencies provide the bulk of out-of-hospital emergency care to children. It
      is imperative, therefore, that all hospital EDs have the appropriate resources
      (medications, equipment, policies, and education) and staff to provide effective
      emergency care for children. This statement outlines resources necessary to
      ensure that hospital EDs stand ready to care for children of all ages, from
      neonates to adolescents. These guidelines are consistent with the recommendations
      of the Institute of Medicine's report on the future of emergency care in the
      United States health system. Although resources within emergency and trauma care
      systems vary locally, regionally, and nationally, it is essential that hospital
      ED staff and administrators and EMS systems' administrators and medical directors
      seek to meet or exceed these guidelines in efforts to optimize the emergency care
      of children they serve. This statement has been endorsed by the American
      Pediatric Association, the American Academy of Family Physicians, American
      Academy of Physician Assistants, American College of Osteopathic Emergency
      Physicians, American College of Surgeons, American Heart Association, American
      Medical Association, Brain Injury Association of America, Child Health
      Corporation of America, Children's National Medical Center, Family Voices,
      National Association of Children's Hospitals and Related Institutions, National
      Association of EMS Physicians, National Association of Emergency Medical
      Technicians, National Association of State EMS Officials, National Committee for
      Quality Assurance, National PTA, Safe Kids USA, Society of Trauma Nurses, The
      Joint Commission, American Pediatric Surgical Association, and Society for
      Academic Emergency Medicine.

PMID- 19769889
TI  - Commentary: moving forward by looking behind you.

PMID- 19769892
TI  - Annals of emergency medicine journal club: frequent fliers, internal and external
      validity, and problems with making continuous variables binary answers to the may
      2009 journal club questions.

PMID- 19769893
TI  - Traumatic eye swelling. Subconjunctival and orbital emphysema with orbital floor
      fracture.

PMID- 19769894
TI  - Performance failure of a colorimetric end-tidal CO2 detector.

PMID- 19769895
TI  - The "1+1" protocol: risks, benefits, and alternatives.

PMID- 19769897
TI  - Laboratory testing and confirmation of suspected measles infection crucial in
      countries that have eliminated measles.

PMID- 19769899
TI  - Emergency physician overhead.

PMID- 19769900
TI  - Considerations for emergency physicians in pre-retirement years.

PMID- 19769901
TI  - Introduction.

PMID- 19769902
TI  - Clinical, anatomic, and imaging correlation in spine-related pain: the essential
      elements.
AB  - Successful treatment of a patient's spine-related pain depends on accurate
      targeting of its location and cause. At a basic level, a focused history and
      physical examination is essential. Understanding of spine anatomy, in particular,
      spine innervation, is fundamental. Correlation with preprocedure imaging is
      important to confirm the suspected location(s) of the pain generator and is
      helpful in planning the approach for image-guided treatment. Understanding the
      variations in spine anatomy, subtle imaging features, or correlates of root
      irritation and factors that can affect the patient's presentation at the time of
      treatment are also critical to accurate targeting and effective treatment. This
      section reviews the fundamental elements that play a role in accurate diagnosis
      of the cause of a patient's spine-related pain. Routine application of these
      basic principles should aid in the approach to the spine-related pain patient and
      improve both accurate targeting of a patient's pain generator and the outcomes of
      image-guided treatment.

PMID- 19769903
TI  - Epidural steroid injections and selective nerve root blocks.
AB  - Epidural steroid injections and lumbar nerve root block/steroid injection are
      commonly performed interventional treatments for spine-related pain. These
      procedures are the foundation of any image-guided spine pain management practice.
      While more generic and not target-specific, epidural steroid injections are
      highly effective in a large proportion of patients, including patients with axial
      pain (neck or low back pain), radiculopathy, or spinal stenosis with neurogenic
      claudication. When isolated lumbar nerve root irritation is more clearly
      suspected, transforaminal nerve root blocks can provide useful diagnostic
      information as well as deliver more specifically targeted steroid treatment.
      Sustained pain relief can be achieved in a substantial number of patients with
      both types of procedure. Here we review the clinical indications and technical
      approach to these fundamental image-guided procedures. Fluoroscopy can be the
      routine approach to all injections. Computed tomography or computed tomographic
      fluoroscopy can be used as the primary approach in lumbar epidural or nerve root
      injections or be used as an alternative technique in unique cases. While the
      basic technical approach to epidural steroid administration in the cervical,
      thoracic, and lumbar regions is similar, each region has unique issues that must
      be addressed.

PMID- 19769904
TI  - Treatment of facet and sacroiliac joint arthropathy: steroid injections and
      radiofrequency ablation.
AB  - Facet and sacroiliac joint arthropathy are common, specific causes of low back
      pain. With a combination of a focused physical examination and image guidance,
      pain originating from these joints can be accurately targeted and these joints
      respond well to the direct application of long-acting deposition preparation
      steroids. When routine steroid treatment of the facet joint is not effective and
      more advanced treatment is required, denervation of the facet joint through the
      use of radiofrequency ablation (RFA) is a preferred method. Image guidance is a
      critical tool in targeting facet joint innervation, performing a central role in
      the techniques used in both preprocedure testing and the RFA treatment. This
      article reviews the basic image-guided fluoroscopic and computed tomographic
      guided approaches to steroid treatment of the facet and sacroiliac joints and
      further discusses of the painful facet through RFA.

PMID- 19769905
TI  - Interventional assessment of the lumbar disk: provocation lumbar diskography and
      functional anesthetic diskography.
AB  - The diagnosis of diskogenic low back pain (LBP) can be elusive. Physical
      examination of the lumbar disk is limited and imaging offers few objective clues.
      While invasive, lumbar diskography is a method available to examine or "provoke"
      the disk directly and determine if LBP is coming from a disk and which disk(s) is
      responsible for the pain. Once identified, features of the abnormal disk can be
      evaluated, including the disk's response to intradiskal local anesthetic and disk
      architecture as observed on diskography imaging and postdiskogram computed
      tomography. Response to anesthetic can be correlated with imaging features
      potentially impacting treatment but can also stand alone as an independent
      objective marker of diskogenic LBP. Here we review the indications for lumbar
      diskography and the basic lumbar diskogram procedure. We also review the
      alternative more advanced technique for studying the anesthetic and mechanical
      features of the disk, functional anesthetic diskography.

PMID- 19769906
TI  - Vertebroplasty and vertebral augmentation techniques.
AB  - Vertebroplasty, the percutaneous administration of acrylic bone cement into a
      vertebral body, was developed in France in 1984, initially as a treatment for a
      painful vertebral hemangioma. Subsequent adaptations of the technique,
      development of materials and devices, and expansion of indications have led to
      many vertebral augmentation variants that have proven highly successful in
      treating pain related to osteoporotic compression fractures and vertebral body
      pathology, such as metastasis and myeloma. Vertebroplasty involves the image
      guided percutaneous placement of a bone access needle into the affected vertebral
      body, followed by injection of the bone cement under intermittent imaging to
      assure appropriate placement of the cement. Supplemental techniques, such as the
      use of a balloon to create a cavity in the vertebral body, and attempt
      restoration of height have also been developed. The indications for the
      procedure, potential risks, and basics of the technique are reviewed here. With
      careful attention to technique, vertebral augmentation is a very safe and highly
      effective treatment for back pain related to vertebral body compression and bony
      pathology.

PMID- 19769907
TI  - Sacroplasty.
AB  - Sacral vertebroplasty, or sacroplasty, entails the percutaneous insertion of 1 or
      more bone needles into the sacral ala and, less commonly, the sacral vertebra
      with fluoroscopic and/or computed tomographic guidance. Acrylic bone cement is
      then injected under imaging guidance to treat the lesion and stabilize the
      sacrum. Sacroplasty is indicated for the treatment of painful sacral
      insufficiency fractures and painful sacral masses, both of which destabilize the
      sacrum. In properly selected patients, sacroplasty is an extremely efficacious
      procedure with a low-risk profile when performed with meticulous imaging guidance
      and a thorough appreciation of the complex sacral anatomy. Complete pain relief
      is observed in the overwhelming majority of patients that are treated for sacral
      insufficiency fractures. While the success rate is lower in patients with painful
      sacral neoplastic lesions, many of these patients experience a reduction in
      analgesic use and a return to ambulation.

PMID- 19769908
TI  - Spinal cord stimulation: a basic approach.
AB  - Chronic back pain and other refractory pain syndromes are a documented burden on
      our society. They also are a huge cost in quality of life and dollars spent on
      health care. Neuromodulation and specifically dorsal column stimulation of the
      spinal cord has been shown to decrease pain with minimal risk to the patient. We
      describe in this article the basic techniques and methods of both the stimulation
      trial and the permanent implantation of the leads and generator. With advanced
      imaging and the minimally invasive approach we further explain how to minimize
      any risk associated with this percutaneous procedure.

PMID- 19769909
TI  - Percutaneous image-guided augmentation for spinal metastatic tumors.
AB  - The purpose of this article is to review the current state of the art for
      treating symptomatic spinal fractures associated with malignant lesions by image
      guided interventional techniques. Epidemiology, clinical presentation, and
      biomechanical ramifications of these lesions are summarized. A suggested
      treatment algorithm is also presented. The second part of the article deals with
      how to approach these lesions, explaining the issues that pertain to patient
      evaluation, preoperative, operative, and postoperative treatment regimes. Tips
      for certain difficult situations and potential complications are also discussed.

PMID- 19769910
TI  - Maintaining health, wellness, and fitness: a new niche for physiatry?

PMID- 19769911
TI  - Action on obesity and fitness: the physiatrist's role.

PMID- 19769913
TI  - Early intra-articular hip disease presenting with posterior pelvic and groin
      pain.
AB  - OBJECTIVE: To determine whether posterior pelvic pain is associated with intra
      articular hip abnormalities (labral tears and early degenerative changes) in
      patients with minimal-to-no radiographic abnormalities. DESIGN: A retrospective
      observational study of prospectively collected data collected from patients with
      an arthroscopy-confirmed diagnosis of acetabular labral tear or femoral and/or
      acetabular chondrosis, without severe deformity. SETTING: An academic orthopedic
      clinic at a tertiary hospital. PATIENTS: All patients, having failed to respond
      to conservative treatment, required surgical intervention for definitive
      structural diagnosis and treatment because of pain and dysfunction. Within this
      group, patients with posterior pelvic pain were included. One hundred thirty
      consecutive patients, 93 women and 37 men with mean age 31.16 years (range, 10
      65.5 years), entered the study, and observational findings were reported.
      INTERVENTIONS: University instructional review board approval was obtained before
      conducting the study. Patients completed medical information questionnaires, pain
      diagrams, severity of pain, and validated hip questionnaires that focused on
      symptoms and function. Postoperatively, patients who had posterior pelvic pain
      before surgery completed a phone interview regarding their clinical progress.
      MAIN OUTCOMES MEASUREMENT: A numeric pain scale, description of location of
      continued pain, Modified Harris Hip Score, and satisfaction with the procedure
      were recorded. RESULTS: Twenty-six (20%) of the 130 patients complained of
      posterior pelvic pain as a component of their clinical presentation. Of these
      patients, the mean duration of symptoms was 29.5 months. A total of 92% related
      that their pain was moderate or marked. The preoperative mean modified Harris Hip
      Score was 61.6 (range, 27-85) and showed postoperative improvement with a mean of
      84.5 (range, 45-100; P < .001). The Modified Harris Hip Score was completed a
      mean 15.9 months postoperatively. Pain diagrams and questionnaires revealed that
      of the 26 patients with posterior pelvic pain, 92.3% (24/26) also had associated
      groin pain (P < .001), 57.7% (15/26) had lateral thigh pain, and 7.7% (2/26) had
      anterior thigh pain (P < .001). A total of 12 of 26 patients with an initial
      presentation including posterior pelvic pain agreed to a phone interview. The
      mean time after surgery in this group of patients was 56.9 months (range, 39-65
      months). Five of 12 patients reported no pain and no activity limitations. The
      Visual Analog Scale representing their self-reported average daily pain was 1.4
      (range, 0-3). The mean Modified Harris Hip Score was 10.4 (range, 8-13). All 7
      patients with continued pain described the pain in more than one location. Ten of
      12 patients were very satisfied with hip arthroscopy, 1 of 12 was somewhat
      satisfied, and 1 of 12 was dissatisfied. This latter patient went on to have
      total hip arthroplasty and was very satisfied with that procedure. All 12
      patients would recommend the procedure to a friend. CONCLUSIONS: Twenty percent
      of patients at the authors' institution who required surgical intervention to
      treat their pain after not responding to conservative management had posterior
      pelvic pain in addition to groin or lateral and anterior hip pain. Of those
      respondents, 33% had complete resolution of symptoms at 4.75 years after surgery,
      and all had reduction in pain as compared with completion of conservative care.
      Patients with early intra-articular hip pathology, such as acetabular labral
      tears with no or mild hip deformity, and patients with arthrosis and mild hip
      deformity may experience groin and posterior pelvic pain as part of their
      clinical presentation.

PMID- 19769912
TI  - The comparative effectiveness of a multimodal program versus exercise alone for
      the secondary prevention of chronic low back pain and disability.
AB  - OBJECTIVE: The objective of this study was to examine whether a multimodal,
      secondary prevention program (MP) is superior to a general physical exercise
      program (EP) in influencing the process leading to chronic low back pain (LBP) in
      nurses with a history of back pain. DESIGN: The study was conducted as a
      randomized controlled parallel-group trial. SETTING: The interventions were
      performed in a single center at the Department of Physical and Rehabilitation
      Medicine at the University of Munich in Germany. PARTICIPANTS: A total of 235
      nurses from 14 nearby hospitals and nursing homes who experienced at least one
      episode of back pain during the previous 2 years were invited into the study. Of
      these, 183 nurses were enrolled and 169 (83 in the MP and 86 in the EP) qualified
      for the intent-to-treat analysis. INTERVENTIONS: The EP consisted of 11 group
      sessions, each lasting 1 hour. After introductory sessions, subsequent sessions
      included general physical strengthening and stretching exercises as well as
      instructions for a home-training program. The MP consisted of 17 group sessions
      of 1.75 hours and one individual session of 45 minutes. In addition to the full
      EP, the MP included 5 psychological units, 7 segmental stabilization exercises
      units, and 8 ergonomic and workplace-specific units. MAIN OUTCOME MEASUREMENTS:
      The primary study end-point variable was pain interference, and the secondary
      study end-point variables were pain intensity and functioning as measured with
      the West Haven-Yale Multidimensional Pain Inventory and the Short Form-36,
      respectively. These study end-point variables were defined a priori. RESULTS:
      There was no statistically significant difference between the 2 groups. Small-to
      moderate effects were observed in both intervention programs across all study end
      point variables. For pain interference, the effect size at 12 months after
      intervention was 0.58 in the MP and 0.47 in the EP. CONCLUSIONS: A multimodal
      program is not superior to a general exercise program in influencing the process
      leading to chronic LBP in a population of nurses with a history of pain. The most
      likely explanation is a common psychological mechanism leading to improved pain
      interference that is irrespective of the program used. Considering the lower
      resources of the general exercise program, the expense for a multimodal program
      is not justified for the secondary prevention of LBP and disability.

PMID- 19769914
TI  - Running shoe selection criteria among adolescent cross-country runners.
AB  - OBJECTIVE: To determine which factors are most important to adolescent cross
      country runners in selecting and replacing running shoes. DESIGN: A cross
      sectional, descriptive survey. SETTING: Surveys were completed at 4 high schools
      in a southeastern Minnesota community. PARTICIPANTS: Eligible subjects included
      adolescents (grades 7-12) participating in cross-country running at any of the 4
      high schools in Rochester, Minnesota. A total of 223 surveys were distributed and
      collected from of an estimated 243 eligible participants. ASSESSMENT OF RISK
      FACTORS: Independent variables included gender, running experience, grade, and
      previous injury history. MAIN OUTCOME MEASURES: A descriptive analysis of factors
      important in running shoe selection was performed. The assessment also included
      evaluation of the runners' knowledge of arch type and awareness of mileage
      accumulated before replacing running shoes. RESULTS: A total of 73.1% of survey
      participants identified arch type compatibility with shoe design as the most
      important factor in choosing a running shoe. However, only 57.0% reported knowing
      their arch type. A total of 74.0% reported not knowing how many miles they
      accumulated in a single pair of running shoes before replacement. CONCLUSIONS: A
      majority of adolescent runners in this study identified arch type and shoe design
      as the most important factors in choosing a running shoe.

PMID- 19769915
TI  - Incongruous changes in heart period and heart rate variability with vagotonic
      atropine: implications for rehabilitation medicine.
AB  - OBJECTIVE: To describe the relationship between vagally mediated bradycardia and
      heart rate variability indices in young and older healthy individuals. DESIGN:
      Cross-sectional, physiologic study. SETTING: Outpatient cardiovascular research
      laboratory. PARTICIPANTS: A total of 34 young (mean age 24 years) and 27 older
      (mean age 63 years) healthy adults. METHODS: Eight bolus injections of atropine
      sulfate were given intravenously to participants while in a supine position
      (cumulative doses from 0.4 to 7.2 microg/kg). Each dose was followed by a 3
      minute data collection period in which subjects controlled their breathing
      frequency at a rate of 15 breaths per minute. MAIN OUTCOME MEASUREMENTS:
      Chronotropic responses were assessed from average RR interval and blood pressure
      was assessed by automated brachial cuff. Heart rate variability (HRV) indices
      were calculated to represent both time domain measures (RR interval standard
      deviation and root mean squared of successive differences) and frequency domain
      measures (respiratory sinus arrhythmia and total power). RESULTS: RR interval
      responses exhibited the expected curvilinear pattern to atropine administration
      with all subjects exhibiting a bradycardia with at least one dose and RR interval
      returning to baseline or decreasing in most subjects as atropine dosing
      progressed. RR interval was closely related to vagotonic atropine dose with an
      r(2) greater than 0.70 in 89% of subjects. Heart rate variability indices were
      not consistently correlated with the bradycardic effect of vagotonic atropine and
      ranged from highly positive to highly negative with almost one-fifth of
      correlations less than 0.5. CONCLUSIONS: The relationship between HRV and vagal
      tone is likely complex and has a large interindividual variation.

PMID- 19769916
TI  - Spastic hypertonia and movement disorders: pathophysiology, clinical
      presentation, and quantification.
AB  - A delayed consequence of a lesion affecting the upper motor neuron pathways is
      the appearance of some forms of motor overactivity, including spasticity. Many of
      these are caused by hyperexcitability of spinal reflexes, such as stretch
      reflexes (spasticity, tendon hyperreflexia) or flexor withdrawal reflexes (flexor
      spasms), and are elicited at rest by sensory stimulation. Spastic co-contraction
      is probably attributable to failure of reciprocal inhibition; it occurs only
      during active voluntary movement and constrains such movement. The basic
      underlying mechanism of these changes is not clear, although a change in the
      balance between the inhibitory and excitatory supraspinal upper motor neuron
      pathways toward net excitation most likely contributes. Increased intrinsic
      excitability of the alpha motor neurons is another possible factor. Spastic
      dystonia is most often seen as the presence of tonic muscle contraction in the
      absence of voluntary movement or spinal reflex activation, and the underlying
      mechanisms are obscure. Prolonged shortening of tissues, either because of
      weakness or muscle contraction, leads to stiffness of the soft tissues, which
      contributes to hypertonia and is thus self-perpetuating, and ultimately to
      contracture with fixed shortening. Some of these forms of motor overactivity
      produce involuntary movements (hyperkinetic), eg, flexor spasms, whereas others
      impair movement (hypokinetic), either voluntary movement, eg, spastic co
      contraction, or passive movement, eg, spasticity. Quantification has mostly
      focused on hypertonia, that is, increased resistance at rest to passive movement.
      In the upper motor neuron syndrome, hypertonia could be caused by a combination
      of spasticity, spastic dystonia, and soft tissue stiffness (rheologic changes).
      Some measures, such as the Ashworth or Modified Ashworth Scales, quantify
      hypertonia but are very poor at distinguishing between spasticity and soft tissue
      stiffness. Another, the Tardieu Scale, is better at making this distinction, but
      quantification of the spasticity portion of hypertonia remains difficult, at
      least in a clinical setting.

PMID- 19769917
TI  - Surgical management of spasticity in persons with cerebral palsy.
AB  - Cerebral palsy is a disorder that primarily affects the neurologic system but
      secondarily affects the musculoskeletal system through the effects of spasticity,
      dystonia, and other movement disorders. The treatment of cerebral palsy requires
      a multidisciplinary approach with treatment aimed at modulating the movement
      disorder through oral medication, injectable drugs (phenol, botulinum toxin), and
      physical and occupational therapy. Treatment of the neurologic effects of the
      central movement disorders include selective dorsal rhizotomy, intrathecal
      baclofen pump placement, and potentially deep brain stimulation. Although any
      effect on tone is temporary, orthopedic surgery has an important role in the
      treatment of the musculoskeletal deformities and contractures present in the
      child with cerebral palsy. Orthopedic surgery improves function by lengthening
      the musculotendinous structures, transferring tendons, performing osteotomies to
      reduce dislocated joints, and normalizing rotation and fusion of selected joints
      to improve stability. Neurosurgical techniques are not as widely used, but may
      reduce spasticity in select individuals. The combined approach of managing tone
      and normalizing the biomechanics of the spine and upper and lower extremities
      through orthopedic surgery and neurosurgery and subsequent rehabilitation is the
      cornerstone of treatment of the child and adult with cerebral palsy.

PMID- 19769918
TI  - Role of oral medications in spasticity management.
AB  - Oral medications are frequently used to manage spasticity. Some clinicians may
      believe that oral medications are a more conservative or "first-line" strategy to
      treat this condition. However, their use may lead to significant adverse events.
      Additionally, efficacy has not been well-established, in particular the ability
      of these medications to enhance functional outcome. The decision regarding the
      use of oral medications is further complicated by the fact that a number of
      different agents have been used for many different diagnoses. The relative dearth
      of well-controlled studies makes the choice of medications for a given clinical
      condition even more difficult. This article reviews the mechanisms of action of
      some of the medications that are more commonly used to treat spasticity and
      identifies some studies that may suggest efficacy, or lack thereof, for certain
      diagnoses. Because questions remain regarding the benefit of oral medications,
      potential side effects also are emphasized to help the reader consider both
      potential risks and benefits. The article is intended as a broad overview, rather
      than comprehensive review of the literature.

PMID- 19769919
TI  - Chemodenervation and nerve blocks in the diagnosis and management of spasticity
      and muscle overactivity.
AB  - This article will discuss many of the key concepts regarding chemodenervation and
      neurolysis in the management of spasticity. Topics that will be discussed include
      techniques for localization, strengths and limitations of various agents
      (botulinum toxin, phenol, and alcohol), the value of combination therapies, and
      the role of nerve blocks (diagnostic and therapeutic). With advancing technology
      have come newer methods to improve accuracy of localization for the performance
      of chemodenervation and neurolysis such as electromyographic guidance, electrical
      stimulation, and ultrasound guidance. During the last 2 decades, the addition of
      botulinum toxin chemodenervation as an adjunct to traditional neurolysis,
      medication, and therapy modalities has expanded the field of treatment of
      intramuscular hyperactivity in upper motor neuron syndrome. The technique of
      diagnostic blocks as predictors of response and the therapeutic value of nerve
      blocks will be discussed.

PMID- 19769920
TI  - Intrathecal baclofen therapy: an update.
AB  - Intrathecal administration of baclofen is a well-established technique for
      modulating hypertonia secondary to upper motor neuron pathology. Despite the
      nearly 2 decades of widespread clinical use, this intervention presents many
      challenges to even experienced clinicians. The purpose of this clinical review is
      to describe some of the intricacies and subtleties of this treatment strategy.
      This narrative provides an overview of 3 topics: (1) an alternative methodology
      for intrathecal baclofen trials; (2) an algorithmic approach to troubleshooting
      intrathecal delivery systems; and (3) the utility of neurophysiologic assessments
      within various phases of intrathecal baclofen therapy.

PMID- 19769921
TI  - Aquatic therapy: scientific foundations and clinical rehabilitation applications.
AB  - The aquatic environment has broad rehabilitative potential, extending from the
      treatment of acute injuries through health maintenance in the face of chronic
      diseases, yet it remains an underused modality. There is an extensive research
      base supporting aquatic therapy, both within the basic science literature and
      clinical literature. This article describes the many physiologic changes that
      occur during immersion as applied to a range of common rehabilitative issues and
      problems. Because of its wide margin of therapeutic safety and clinical
      adaptability, aquatic therapy is a very useful tool in the rehabilitative
      toolbox. Through a better understanding of the applied physiology, the
      practitioner may structure appropriate therapeutic programs for a diverse patient
      population.

PMID- 19769922
TI  - Putting P values in perspective.

PMID- 19769923
TI  - Single-specialty versus multispecialty group employment.

PMID- 19769924
TI  - A case of suspected mononeuritis multiplex in a teenager from polysubstance
      abuse.

PMID- 19769925
TI  - Radicular pain in a patient with aqueductal cerebral stenosis.

PMID- 19769926
TI  - Copper deficiency anemia and neutropenia in a jejunostomy-fed patient.

PMID- 19769927
TI  - Thoracic osteomyelitis: an easily missed diagnosis.

PMID- 19769928
TI  - Evidence-based conviction.

PMID- 19769929
TI  - The genus Laetiporus (Basidiomycota, Polyporales) in East Asia.
AB  - Relationships among East Asian, North American and European Laetiporus sulphureus
      s. lat., a cosmopolitan brown rot species complex, were assessed with
      phylogenetic analyses and incompatibility tests. Three East Asian taxa,
      Laetiporus cremeiporus sp. nov., Laetiporus montanus and Laetiporus versisporus,
      are described and illustrated as well as compared with related taxa from
      Southeast Asia, North America and Europe. Phylogenetic analyses showed that L.
      cremeiporus and L. versisporus are clearly distinct species among Laetiporus
      taxa. The three conifer inhabiting species, Laetiporus conifericola, Laetiporus
      huroniensis and L. montanus, are closely related to each other. The European
      population of L. montanus exhibits two sequence variants of the EF1alpha: one is
      the same as observed in L. sulphureus in Europe and the other is that observed in
      East Asian population of L. montanus. A key to the known species of Laetiporus in
      the northern hemisphere is provided.

PMID- 19769930
TI  - Subchondral bone marrow lesions are highly associated with, and predict
      subchondral bone attrition longitudinally: the MOST study.
AB  - OBJECTIVE: Subchondral bone attrition (SBA) is defined as flattening or
      depression of the osseous articular surface. The causes of attrition are unknown,
      but remodeling processes due to chronic overload that are reflected as bone
      marrow edema-like lesions (BMLs) on magnetic resonance imaging (MRI) might
      predispose the subchondral bone to subsequent attrition. The aim of this study
      was to evaluate the cross-sectional and longitudinal association of BMLs with SBA
      in the same subregion of the knee. DESIGN: The Multicenter Osteoarthritis (MOST)
      study is a longitudinal observational study of individuals who have or are at
      high risk for knee osteoarthritis. Subjects with available baseline and 30-months
      follow-up MRI were included. Patients with a recent history of trauma or findings
      suggestive of post-traumatic bone marrow changes were excluded. Subchondral BMLs
      and SBA were scored semiquantitatively from 0 to 3 in 10 tibiofemoral subregions.
      We evaluated the association of prevalent BMLs at baseline with the presence of
      prevalent and incident SBA on a per-subregion basis using logistic regression. We
      also cross-sectionally evaluated the association of BML grade severity and
      presence of baseline SBA. RESULTS: One thousand and twenty-five knees were
      included. 8.9% of the analyzed knee subregions showed SBA present at baseline and
      9.2% of subregions exhibited prevalent subchondral BMLs. The adjusted odds ratio
      (OR) for prevalent SBA for subregions with prevalent BMLs was 18.8 [95%
      confidence intervals (CI) 15.9-22.4]. A larger BML size was directly associated
      with an increased risk of prevalent SBA. 195 (2.2%) subregions exhibited incident
      SBA at follow-up. The adjusted OR for incident SBA was 5.3 [95% CI 3.6-7.7] when
      compared to subregions without BMLs as the reference. CONCLUSIONS: Prevalent and
      incident SBA is strongly associated with subchondral BMLs in the same subregion.
      One explanation for the presence and development of SBA is subchondral remodeling
      due to increased stress, which is reflected as BMLs on MRI.

PMID- 19769931
TI  - Two novel ternary albendazole-cyclodextrin-polymer systems: dissolution,
      bioavailability and efficacy against Taenia crassiceps cysts.
AB  - The effect of two water-soluble polymers: pectin and polyvinylpyrrolidone in
      combination with beta-cyclodextrin, on the dissolution, bioavailability and
      cysticidal efficacy of albendazole was evaluated using a commercial suspension as
      reference product. The dissolution of the albendazole-beta-cyclodextrin-pectin
      formulation was slow and incomplete (44.7%). No statistical differences in C(max)
      and AUC were found between this formulation and the reference. Also its
      cysticidal efficacy (33%) was similar to the reference (38%). The albendazole
      beta-cyclodextrin-polyvinylpyrrolidone formulation exhibited the highest
      dissolution rate (78.5%) and its bioavailability was also significantly increased
      (2.3-fold). In addition, the cysticidal activity of this formulation (83%) was
      greater than a commercial suspension. Our results suggest that the ternary system
      of albendazole-beta-cyclodextrin-polyvinylpyrrolidone could be a potential
      alternative for the treatment of systemic helmintic diseases and it is worth to
      continue its preclinical evaluation.

PMID- 19769932
TI  - PCR for diagnosis and assessment of cure in kala-azar patients in Bangladesh.
AB  - The study evaluated the usefulness of Leishmania-nested polymerase chain reaction
      (Ln-PCR) for diagnosis of kala-azar and assessed its role as a test of cure among
      kala-azar patients in Bangladesh. Peripheral blood buffy coat Ln-PCR was done in
      ninety-seven (97) clinically suspected patients of kala-azar, in forty (40)
      healthy controls from both endemic and non-endemic areas, and in forty-six (46)
      patients after completion of treatment with sodium stibogluconate (SSG). The Ln
      PCR results were compared with Leishmania donovani parasite load graded by 1+ to
      6+ in all smear-positive L. donovani cases. Out of 97 clinically suspected kala
      azar patients, 94 were parasitologically confirmed. Ln-PCR was found positive in
      91 of 94 parasitologically positive patients of kala-azar at diagnosis,
      indicating its diagnostic sensitivity as 97%. None of the controls was found
      positive for Ln-PCR, indicating its diagnostic specificity to be 100%. About 9%
      of kala-azar patients having been graded 1+ parasitic load had negative Ln-PCR
      results. After completion of treatment, Ln-PCR was positive in 4 patients (8.4%)
      out of 46 cases, indicating its role in demonstrating the absence of parasites 30
      days after completion of treatment in 91.6% of the treated patients. This limited
      study suggests that Ln-PCR is a highly sensitive and specific test for the
      diagnosis of visceral leishmaniasis and can be used as a test of cure. Thus,
      efforts should be made to establish this useful method at least in the tertiary
      care hospitals and, if possible, at the district-level hospitals, especially in
      the endemic areas of Bangladesh.

PMID- 19769933
TI  - In vitro biological evaluation of biguanides and dihydrotriazines against Brugia
      malayi and folate reversal studies.
AB  - Dihydrofolate reductase (DHFR) is a well-known target for antibacterial and
      anticancer therapy. DHFR inhibitors are useful for protozoan parasites, but are
      yet to be explored against metazoan species; hence the present work was designed
      to evaluate the efficacy of DHFR inhibitors against filariasis, one of the major
      neglected tropical diseases. Molecules from our in-house library of synthetic
      antifolate agents (biguanide and dihydrotriazine derivatives) were evaluated
      along with the antimalarial drug pyrimethamine and the antibacterial drug
      trimethoprim in an in vitro model against Brugia malayi microfilariae (Mf). Three
      biguanides and two dihydrotriazines were more potent than trimethoprim and
      pyrimethamine against B. malayi Mf. Trimethoprim, pyrimethamine and four of the
      five compounds active against Mf were also active against adult worms. To probe
      the mechanism of action of the compounds, reversal of activity of active
      compounds by folic acid and folinic acid was studied. In conclusion, DHFR
      inhibitors could be used as leads for new antifilarial drugs.

PMID- 19769934
TI  - Identification of a novel 19 kDa Echinococcus granulosus antigen.
AB  - By screening an Echinococcus granulosus cDNA library with IgG4 from patients with
      active cystic echinococcosis (CE), we identified a cDNA encoding a protein of
      19.0 kDa (Eg19). Eg19, in 12% SDS-PAGE in reducing and non-reducing conditions,
      showed several bands between 19 and 100 kDa. Immunoblotting (IB) analysis
      detected total IgG, IgG1 and IgG4 specific to the 38/40 kDa band of Eg19 in the
      10% of patients' sera. The percentage of total IgG, IgG1 and IgG4-positive sera
      were significantly higher in sera from patients with active disease and cyst in
      multiple sites than from patients with inactive disease and cyst in the liver
      (P<10(-4)). ELISA analysis disclosed that during the follow-up anti-Eg19 antibody
      concentration decreased over the course of treatment in sera from patients with
      cured disease. Even if Eg19 appear to have no benefit in the diagnosis of the
      disease, our data, confirming the presence of antigens inducing both IgG1 and
      IgG4 during active development of CE, suggest that Eg19 might be a marker of
      disease status.

PMID- 19769935
TI  - High-performance liquid chromatography and on-line mass spectrometry detection
      for the analysis of chondroitin sulfates/hyaluronan disaccharides derivatized
      with 2-aminoacridone.
AB  - In this study, we developed an on-line reverse-phase high-performance liquid
      chromatography-electrospray ionization-mass spectrometry (RP-HPLC-ESI-MS)
      separation and structural characterization of hyaluronan (HA)/chondroitin sulfate
      (CS)/dermatan sulfate (DS) disaccharides released by enzymatic treatment and
      derivatized with 2-aminoacridone (AMAC), providing a high-resolution system also
      applicable by using a further fluorimetric detector (Fp) before ESI-MS spectral
      acquisition. Isomeric nonsulfated HA and CS/DS disaccharides, isomeric
      monosulfated and isomeric disulfated CS/DS disaccharides, and the trisulfated
      species were distinctly separated and unambiguously identified by their retention
      times and mass spectra in negative ionization mode. In general, no multiply
      charged ions were detected even for highly charged disaccharides, but the
      presence of desulfonated products for highly sulfated species due to the relative
      instability of sulfo groups was observed. RP-HPLC-ESI-MS of each AMAC
      disaccharide was found to be linear from 3 to 500 ng with very high coefficient
      of correlation values due to the high efficiency of separation and the sharp
      outline of the peaks. Various CS/DS samples were characterized for disaccharide
      composition, and minor oligomer species identified as GalNAcSO(4) at the
      nonreducing end of chains was observed as a common component of these
      macromolecules. Furthermore, purified endogenous normal human plasma CS
      disaccharides were also evaluated by means of RP-HPLC-(Fp)-ESI-MS.

PMID- 19769936
TI  - Ultraperformance liquid chromatography with electrospray ionization ion trap mass
      spectrometry for chondroitin disaccharide analysis.
AB  - Chondroitin sulfate (CS) has an important role in cell division, in the central
      nervous system, and in joint-related pathologies such as osteoarthritis. Due to
      the complex chemical structure and biological importance of CS, simple,
      sensitive, high resolution, and robust analytical methods are needed for the
      analysis of CS disaccharides and oligosaccharides. An ion-pairing, reversed
      phase, ultraperformance liquid chromatography (IPRP-UPLC) separation, coupled to
      electrospray ionization mass spectrometry with an ion trap mass analyzer, was
      applied for the analyses of CS-derived disaccharides. UPLC separation technology
      uses small particle diameter, short column length, and elevated column
      temperature to obtain high resolution and sensitivity. Hexylamine (15 mM) was
      selected as the optimal ion-pairing reagent.

PMID- 19769937
TI  - Role of naturally occurring osmolytes in protein folding and stability.
AB  - Osmolytes are typically accumulated in the intracellular environment at
      relatively high concentrations when cells/tissues are subjected to stress
      conditions. Osmolytes are common in a variety of organisms, including
      microorganisms, plants, and animals. They enhance thermodynamic stability of
      proteins by providing natively folded conformations without perturbing other
      cellular processes. By burying the backbone into the core of folded proteins,
      osmolytes can provide significant stability to proteins. Two properties of
      osmolytes are particularly important: (i) their ability to impart increased
      thermodynamic stability to folded proteins; and (ii) their compatibility in the
      intracellular environment at high concentrations. Under physiological conditions,
      the cellular compositions of osmolytes may vary significantly. This may lead to
      different protein folding pathways utilized in cells depending upon the
      intracellular environment. Proper understanding of the role of osmolytes in cell
      regulation should allow predicting the action of osmolytes on macromolecular
      interactions in stressed and crowded environments typical of cellular conditions.

PMID- 19769938
TI  - Usual and unusual biochemical properties of ADF/cofilin-like protein Adf73p in
      ciliate Tetrahymena thermophila.
AB  - Actin-depolymerizing factor (ADF)/cofilin is a well-conserved actin-modulating
      protein, which induces reorganization of the actin cytoskeleton by severing and
      depolymerizing F-actin. ADF/cofilin also binds to G-actin and inhibits nucleotide
      exchange, and hence, is supposed to regulate the nucleotide-bound state of the
      cellular G-actin pool cooperating with profilin, another well-conserved G-actin
      binding protein that promotes nucleotide exchange. In this report, we
      investigated the biochemical properties of the ADF/cofilin-like protein Adf73p
      from ciliate Tetrahymena thermophila. Adf73p also binds to both G- and F-actin
      and severs and depolymerizes F-actin. Unlike canonical ADF/cofilin, however,
      Adf73p accelerates nucleotide exchange on actin and allows repolymerization of
      disassembled actin. These results suggest that the actin cytoskeleton of T.
      thermophila is regulated by Adf73p in a different way from those of mammals,
      plants, and yeasts.

PMID- 19769939
TI  - Evolutionary complexities of swine flu H1N1 gene sequences of 2009.
AB  - A recently emerged novel influenza A (H1N1) virus continues to spread globally.
      The pandemic caused by this new H1N1 swine influenza virus presents an
      opportunity to analyze the evolutionary significance of the origin of the new
      strain of swine flu. Our study clearly suggests that strong purifying selection
      is responsible for the evolution of the novel influenza A (H1N1) virus among
      human. We observed that the 2009 viral sequences are evolutionarily widely
      different from the past few years' sequences. Rather, the 2009 sequences are
      evolutionarily more similar to the most ancient sequence reported in the NCBI
      Influenza Virus Resource Database collected in 1918. Analysis of evolutionary
      rates also supports the view that all the genes in the pandemic strain of 2009
      except NA and M genes are derived from triple reassorted swine viruses. Our study
      demonstrates the importance of using complete-genome approach as more sequences
      will become available to investigate the evolutionary origin of the 1918
      influenza A (H1N1) swine flu strain and the possibility of future reassortment
      events.

PMID- 19769940
TI  - MicroRNA isolation and stability in stored RNA samples.
AB  - MicroRNAs (miRNAs) are small RNA molecules, which act as post-transcriptional
      regulators of a gene expression, with important functions within the cell
      physiology. Whilst many authors have focused on the study of miRNA expression in
      physiological and pathological processes, various technical variables related to
      miRNA isolation have simultaneously emerged and the stability of the stored miRNA
      samples has been questioned. A robust method for RNA isolation is essential for
      reproducible results and miRNAs instability in the stored samples would make for
      an alarming situation for most expression studies. Here these issues are
      discussed and we investigate the stability of miRNAs isolated from clinical
      samples of B lymphocytes (chronic lymphocytic leukemia) by the most commonly
      utilized method based on a Trizol/TRI-Reagent solution (RNAs stored at -80
      degrees C). To assess the stability of miRNAs, a Real Time-PCR analysis was
      performed for a panel of 29 miRNAs from a freshly isolated RNA sample and after
      14 days storage at -80 degrees C. Furthermore, a Real Time-PCR analysis was
      repeatedly performed for a stored RNA sample over a period of approximately 10
      months. We observed high stability of isolated miRNAs and respective cDNAs. The
      reproducibility and efficiency of the Trizol/TRI-Reagent isolation method was
      also tested and compared to the mirVana Isolation kit (Ambion) and RNeasy kit
      (Qiagen). In conclusion, Trizol/TRI-Reagent based isolation is a robust
      reproducible method, and obtained miRNA samples do not show any tendency to
      degradation when properly stored and handled.

PMID- 19769941
TI  - Activin inhibits telomerase activity in cancer.
AB  - Activin is a pleiotropic cytokine with broad tissue distributions. Recent studies
      demonstrate that activin-A inhibits cancer cell proliferation with unknown
      mechanisms. In this report, we demonstrate that recombinant activin-A induces
      telomerase inhibition in cancer cells. In breast and cervical cancer cells,
      activin-A resulted in telomerase activity in a concentration-dependent manner.
      Significant inhibition was observed at 10 ng/ml of activin-A, with a near
      complete inhibition at 80 ng/ml. Consistently, activin-A induced repression of
      the telomerase reverse transcriptase (hTERT) gene, with the hTERT gene to be
      suppressed by 60-80% within 24h. In addition, activin-A induced a concomitant
      increase in Smad3 signaling and decrease of the hTERT gene promoter activity in a
      concentration-dependent fashion. These data suggest that activin-A triggered
      telomerase inhibition by down-regulating hTERT gene expression is involved in
      activin-A-induced inhibition of cancer cell proliferation.

PMID- 19769942
TI  - Escape mechanisms from antibody therapy to lymphoma cells: downregulation of CD20
      mRNA by recruitment of the HDAC complex and not by DNA methylation.
AB  - Although rituximab is a critical monoclonal antibody therapy for CD20-positive B
      cell lymphomas, rituximab resistance showing a CD20-negative phenotypic change
      has been a considerable clinical problem. Here we demonstrate that CD20 mRNA and
      protein expression is repressed by recruitment of a histone deacetylase protein
      complex to the MS4A1 (CD20) gene promoter in CD20-negative transformed cells
      after treatment with rituximab. CD20 mRNA and protein expression were stimulated
      by decitabine (5-Aza-dC) in CD20-negative transformed cells, and was enhanced by
      trichostation A (TSA). Immunoblotting indicated that DNMT1 expression was first
      downregulated 1 day after treatment with 5-Aza-dC, but IRF4 and Pu.1, the
      transcriptional regulators of MS4A1, were still expressed with or without 5-Aza
      dC. Interestingly, CpG methylation of the MS4A1 promoter was not observed in CD20
      negative transformed cells without 5-Aza-dC. A chromatin immunoprecipitation
      (ChIP) assay indicated that the Sin3A-HDAC1 co-repressor complex was recruited to
      the promoter and dissociated from the promoter with 5-Aza-dC and TSA, resulting
      in histone acetylation. Under these conditions, IRF4 and Pu.1 were continually
      recruited to the promoter with or without 5-Aza-dC and TSA. These results suggest
      that recruitment of the Sin3A-HDAC1 complex is related to downregulation of CD20
      expression in CD20-negative B-cells after treatment with rituximab.

PMID- 19769943
TI  - Codon usage and gene expression pattern of Stenotrophomonas maltophilia R551-3
      for pathogenic mode of living.
AB  - Stenotrophomonas maltophilia strain R551-3 is a multiple-antibiotic-resistant
      opportunistic human pathogen involved in nosocomial infections. It has a widely
      distributed GC-rich (>66%) genome. Analysis of differential expression of the
      genes of this genome reveals that majority of genes belonging to highly expressed
      category are mostly present on lagging strand without showing any strand specific
      codon usage bias. Relatively small number of lowly expressed genes is equally
      distributed on both leading and lagging strands with a difference in codon usage
      pattern between them. Among several multi drug resistance genes of S. maltophilia
      involving lowly expressed category some are predicted as horizontally
      transferred. It can be inferred that horizontally transferred genes may have been
      imported into this genome for their pathogenic mode of living. Our study may help
      to modify the expression level of the target genes of this human pathogen in
      order to control its infection.

PMID- 19769944
TI  - Prostaglandin EP3 receptor superactivates adenylyl cyclase via the Gq/PLC/Ca2+
      pathway in a lipid raft-dependent manner.
AB  - We previously demonstrated that prostaglandin EP3 receptor augments EP2-elicited
      cAMP formation in COS-7 cells in a G(i/o)-insensitive manner. The purpose of our
      current study was to identify the signaling pathways involved in EP3-induced
      augmentation of receptor-stimulated cAMP formation. The enhancing effect of EP3
      receptor was irrespective of the C-terminal structure of the EP3 isoform. This
      EP3 action was abolished by treatment with inhibitors for phospholipase C and
      intracellular Ca(2+)-related signaling molecules such as U73122, staurosporine, 2
      APB and SK&F 96365. Indeed, an EP3 agonist stimulated IP(3) formation and
      intracellular Ca(2+) mobilization, which was blocked by U73122, but not by
      pertussis toxin. The enhancing effect by EP3 on cAMP formation was mimicked by
      both a Ca(2+) ionophore and the activation of a typical G(q)-coupled receptor.
      Moreover, EP3 was exclusively localized to the raft fraction in COS-7 cells and
      EP3-elicited augmentation of cAMP formation was abolished by cholesterol
      depletion and introduction of a dominant negative caveolin-1 mutant. These
      results suggest that EP3 elicits adenylyl cyclase superactivation via
      G(q)/phospholipase C activation and intracellular Ca(2+) mobilization in a lipid
      raft microdomain-dependent manner.

PMID- 19769945
TI  - Withaferin A targets heat shock protein 90 in pancreatic cancer cells.
AB  - The purpose of this study is to investigate the efficacy and the mechanism of
      Hsp90 inhibition of Withaferin A (WA), a steroidal lactone occurring in Withania
      somnifera, in pancreatic cancer in vitro and in vivo. Withaferin A exhibited
      potent antiproliferative activity against pancreatic cancer cells in vitro (with
      IC(50)s of 1.24, 2.93 and 2.78 microM) in pancreatic cancer cell lines Panc-1,
      MiaPaCa2 and BxPc3, respectively. Annexin V staining showed that WA induced
      significant apoptosis in Panc-1 cells in a dose-dependent manner. Western
      blotting demonstrated that WA inhibited Hsp90 chaperone activity to induce
      degradation of Hsp90 client proteins (Akt, Cdk4 and glucocorticoid receptor),
      which was reversed by the proteasomal inhibitor, MG132. WA-biotin pull down assay
      of Hsp90 using Panc-1 cancer cell lysates and purified Hsp90 showed that WA
      biotin binds to C-terminus of Hsp90 which was competitively blocked by unlabeled
      WA. Co-immunoprecipitation exhibited that WA (10 microM) disrupted Hsp90-Cdc37
      complexes from 1 to 24h post-treatment, while it neither blocked ATP binding to
      Hsp90, nor changed Hsp90-P23 association. WA (3, 6mg/kg) inhibited tumor growth
      in pancreatic Panc-1 xenografts by 30% and 58%, respectively. These data
      demonstrate that Withaferin A binds Hsp90, inhibits Hsp90 chaperone activity
      through an ATP-independent mechanism, results in Hsp90 client protein
      degradation, and exhibits in vivo anticancer activity against pancreatic cancer.

PMID- 19769947
TI  - Src-mediated regulation of inflammatory responses by actin polymerization.
AB  - Although the role of the actin cytoskeleton has become increasingly elucidated,
      the role of actin polymerization in inflammatory processes remains poorly
      understood. Here, we examine the role of the actin cytoskeleton during LPS
      mediated inflammatory events in RAW264.7 cells and peritoneal macrophages. We
      observed that actin cytoskeleton disruption by cytochalasin B and siRNA to
      cytoplasmic actin strongly down-regulated LPS-mediated inflammatory responses
      such as NO production, PGE(2) release, and TNF-alpha secretion. Actin
      cytoskeleton disruption by cytochalasin B down-regulated a series of signaling
      cascades including PI3K, Akt, and IKK, but not MAPKs, necessary for NF-kappaB
      activation without down-regulating total forms of the proteins as assessed by
      measuring their phosphorylation levels. In particular, cytochalasin B
      significantly inhibited LPS-induced both phosphorylation and kinase activity of
      Src without altering total level, implying that Src may be a potential
      pharmacological target of actin cytoskeleton rearrangement. Moreover, the direct
      association of Src with actin was actin polymerization-dependent according to
      immunoprecipitation analysis performed with a GFP-actin wild type and HA-tagged
      Src. Therefore, our data suggest that actin cytoskeleton rearrangement may be a
      key event during the regulation of inflammatory responses that modulates the
      activity of Src and its downstream signaling molecules.

PMID- 19769946
TI  - 2-(3,4-Dihydro-2H-pyrrolium-1-yl)-3oxoindan-1-olate (DHPO), a novel, synthetic
      small molecule that alleviates insulin resistance and lipid abnormalities.
AB  - Type-2 diabetes is growing at epidemic proportions world-wide. This report
      describes the effect of a novel, synthetic, small molecule 2-(3,4-dihydro-2H
      pyrrolium-1-yl)-3oxoindan-1-olate (DHPO), on metabolic abnormalities in genetic
      and dietary mouse models of type-2 diabetes. DHPO (20mg/kg/d i.p. for 21 days)
      attenuated fasting blood glucose, improved glucose disposal and corrected
      dyslipidemia in genetic (leptin deficient, ob/ob) and dietary (high-fat-fed)
      mouse models of insulin resistance. In addition, DHPO augmented 2-deoxy-d-glucose
      (2DG) uptake in gastrocnemius muscles of wild-type mice and in cultured myotubes.
      The increase in 2DG-uptake was associated with an increase in the phosphorylation
      of AMPK (thr-172) and its downstream effector acetyl-CoA carboxylase without any
      changes in the phosphorylation of Akt of insulin receptor. The AMPK inhibitor,
      compound C attenuated DHPO-induced glucose-uptake whereas the PI3-kinase
      inhibitor Wortmannin was less effective. In addition, DHPO failed to augment
      glucose-uptake in the gastrocnemius muscle from AMPK-alpha2-transgenic (kinase
      dead) mice. Taken together, these results suggest that DHPO is a novel small
      molecule that alleviates impaired glucose tolerance and lipid abnormalities
      associated with type-2 diabetes.

PMID- 19769949
TI  - Neuroendocrine responses in neonatal mother-deprived rabbits.
AB  - To study both short- and long-term adaptation mechanisms activated by rabbits
      which were separated from their mothers (DLS) for 48 h between postnatal days 9
      and 11, we examined plasma corticosterone concentrations before, during, and
      after DLS as well as the expression of glucocorticoid receptor (GR) in the
      hippocampus and the adrenal axis responses to a mild stress stimuli or exogenous
      ACTH injection. At postnatal day 10, plasma corticosterone concentration of DLS
      rabbits was similar to that of controls, but rose two-fold at day 11 (17.7 + or -
      1.3 vs. 9.3 + or - 1.2 microg/dl, P<0.01) and then decreased at day 12, when
      suckling was allowed again, to match those of controls with no difference
      thereafter. At postnatal day 14, both control and DLS rabbits had similar basal
      corticosterone concentrations (2.2 + or - 0.4 vs. 2.3 + or - 1.1 microg/dl,
      respectively) as well as at day 120 (8.8 + or - 3.2 vs. 9.7 + or - 2.8 microg/dl,
      respectively). After the standardized stress stimulus, plasma corticosterone
      concentrations were lower in DLS rabbits than controls at postnatal days 14
      (P<0.01) and 120 (P<0.05). At day 120, corticosterone levels rose similarly seven
      fold (P<0.01) within 30 min after ACTH administration and remained sustained
      thereafter in both control and DLS rabbits. Positive immunoreactivity for GR was
      detected in the hippocampus and in the dorsal medial hypothalamic region at
      postnatal day 14. The present data suggest that 48 h DLS from postnatal days 9 to
      11 results in a modified hypothalamic-pituitary-adrenal axis reactivity later in
      life.

PMID- 19769948
TI  - Prolactin induces Egr-1 gene expression in cultured hypothalamic cells and in the
      rat hypothalamus.
AB  - Prolactin (PRL), the major lactogenic hormone, acts also as neuromodulator and
      regulator of neuronal and glial plasticity in the brain. There is an increase in
      synthesis and release of PRL within the hypothalamus during peripartum and in
      response to stress. To identify mechanisms by which PRL induces neuroplasticity,
      we studied the ability of PRL to induce the transcription factor Egr-1 in the
      hypothalamic cell line, 4B, in vitro, and in specific neuronal cell types of the
      hypothalamus in vivo. PRL induced Egr-1 mRNA expression in 4B cells, an effect
      which was prevented by the MEK inhibitor, U0126. In vivo, intracerebroventricular
      PRL (1 microg) increased Egr-1 mRNA levels in the hypothalamic paraventricular
      (PVN) and supraoptic nuclei (SON) of female rats. The increase in mRNA paralleled
      elevated Egr-1 protein expression in the PVN and SON. Double staining
      immunohistochemistry revealed Egr-1 localization in oxytocin neurons of the PVN
      and SON, but not in vasopressin neurons in these regions. In the dorsomedial PVN,
      a population of non-oxytocin or vasopressin cells localized in a region
      corresponding to corticotropin-releasing hormone neurons also showed marked Egr-1
      immunoreactivity. The data suggest that PRL modulates plasticity in oxytocinergic
      neurons, through MAP kinase-dependent induction of Egr-1.

PMID- 19769950
TI  - MDMA (ecstasy) modulates locomotor and prefrontal cortex sensory evoked activity.
AB  - Ingestion of 3, 4-methylenedioxymethamphetamine (MDMA) leads to heightened
      response to sensory stimulation; thus, MDMA is referred to as "ecstasy" because
      it produces pleasurable enhancement of such sensation. There have been no
      electrophysiological studies that report the consequences of MDMA on sensory
      input. The present study was initiated to study the effects of acute and chronic
      MDMA on locomotor activity and sensory evoked field potential from freely
      behaving rats previously implanted with permanent electrodes in the prefrontal
      cortex (PFC). The main findings of this study are that: (1) acute MDMA augments
      locomotor behavior and attenuates the incoming sensory input, (2) chronic
      treatment of MDMA elicits behavioral sensitization, (3) chronic administration of
      MDMA results in attenuation of the baseline activity of the sensory evoked field
      potential, and (4) administration of rechallenge MDMA result in enhancement of
      the PFC sensory evoked field potential.

PMID- 19769951
TI  - Putative antinociceptive action of nitric oxide in the caudal part of the spinal
      trigeminal nucleus during chronic carrageenan-induced arthritis in the rat
      temporomandibular joint.
AB  - In order to investigate a putative role for nitric oxide (NO) in the central
      nociceptive processing following carrageenan-induced arthritis in the rat
      temporomandibular joint (TMJ), we analyzed the immunoreactivity, gene expression
      and activity of nitric oxide synthases (NOS) in the caudal part of the spinal
      trigeminal nucleus (Sp5C) during the acute (24 h), chronic (15 days) and chronic
      active (14 days-24 h) arthritis. In addition, evaluation of head-withdrawal
      threshold was carried out in all phases of arthritis under chronic inhibition of
      nNOS with the selective inhibitor 7-nitroindazole (7-NI). Neurons with nNOS-like
      immunoreactivity (nNOS-LI) were concentrated mainly in the lamina II of the Sp5C,
      showing no significant statistical difference during arthritis. Only a discrete
      percentage of nNOS-LI neurons expressed Fos immunoreactivity. The mRNA expression
      for both nNOS and endothelial nitric oxide synthases (eNOS) presented no
      noticeable differences among the groups. No expression of inducible nitric oxide
      synthase (iNOS) was detected in the Sp5C by either immunohistochemistry or
      reverse-transcription polymerase chain reaction (RT-PCR). Ca(2+)-dependent NOS
      activity in the ipsilateral Sp5C was significantly higher (108.3+/-49.2%; P<0.01)
      in animals during the chronic arthritis. Interestingly, this increased activity
      was completely abolished 24 h later, in the chronic-active arthritis. Finally,
      head-withdrawal threshold decreased significantly in the chronic arthritis in
      animals under 7-NI chronic inhibition. In conclusion, nNOS immunoreactivity and
      mRNA expression are stable in the Sp5C during TMJ arthritis evolution, but its
      activity significantly increases in the chronic-phases supporting an
      antinociceptive role of the nNOS as evidenced by pain threshold experiment.

PMID- 19769952
TI  - The ability of stress to alter sleep in mice is sensitive to reproductive
      hormones.
AB  - Though stress causes complex sleep disruptions that are different in females and
      males, little is known about how sex influences the ability of stress to alter
      sleep. To date there have been no comprehensive examinations of whether effects
      of stress on sleep are sensitive to determinants of sex, such as reproductive
      hormones. Since restraint stress produces a sexually dimorphic increase in rapid
      eye movement sleep (REMS) amount in mice that is greater in males than females,
      in the current study we sought to determine whether estrogens and androgens
      influence the ability of restraint stress to alter sleep states. We removed the
      gonads from adult female and male C57BL/6J mice and implanted the mice with
      recording electrodes to monitor sleep-wake states. Gonadectomized females and
      males exhibited similar amounts of REMS in response to restraint stress. Mice
      were then implanted with continuous release hormone pellets. Females received
      17beta-estradiol and males received testosterone. Hormone replacement (HR) in
      females decreased the REMS response to restraint stress while HR in males
      increased the REMS response to restraint stress. The combined effects of HR in
      females and males restored the sex difference in the ability of restraint stress
      to alter REMS. These results demonstrate that sex differences in the effects of
      stress on REMS are dependent on reproductive hormones and support the view that
      endogenous or exogenous changes in the reproductive hormone environment influence
      sleep responses to stress.

PMID- 19769953
TI  - Performance of a new interference-resistant glucose meter.
AB  - OBJECTIVES: Glucose meters are widely used in self and hospital monitoring of
      blood glucose. We examined the analytical performance of a StatStrip glucose
      monitoring system. DESIGN AND METHODS: Linearity, % recovery and within-run
      imprecision were studied using glucose-spiked whole blood. A total of 120
      heparinized samples were used in method comparison using a plasma hexokinase on
      the Dimension RxL MAX analyzer as the comparison method. Common interferences
      were tested on the StatStrip, Accu-Chek Advantage and the MediSense Optium
      glucose meters at low, middle and high glucose levels. RESULTS: The StatStrip
      assay showed excellent linearity and recovery. The coefficient of variations for
      imprecision were <5%. This meter correlated well with the comparison method
      (y=0.994X+0.03; r=0.995, S(y/x)=0.05 mmol/L, bias=-0.01 mmol/L). Of the three
      meters tested, only the StatStrip showed interference <10% for all spiked levels
      of acetaminophen, ascorbic acid, maltose and hematocrit at three levels of
      glucose tested. CONCLUSIONS: The StatStrip meter showed good performance and is
      suitable for point-of-care hospital glucose testing.

PMID- 19769954
TI  - Effect of albumin concentration and serum matrix on ischemia-modified albumin.
AB  - OBJECTIVES: There is concern that ischemia-modified albumin (IMA) levels measured
      by albumin cobalt binding (ACB) assay reflect mainly albumin concentrations
      rather than myocardial ischemia. DESIGN AND METHODS: Serum matrix and proteins
      were separated from a serum pool by a membrane filter. Two series of pools with
      albumin concentrations of 10, 20, 30, 40, 50, and 60 g/L were prepared either
      with human albumin or serum protein fraction. IMA values of these pools were
      measured in quintiplicate. RESULTS: There was a strong negative correlation
      between IMA and albumin levels in both pools. IMA change corresponding to each 10
      g/L difference in albumin concentration was 37% and 48% in these pools.
      CONCLUSIONS: ACB assay reflects albumin concentrations rather than IMA. Primary
      predictor of IMA in serum matrix is albumin concentration.

PMID- 19769955
TI  - Genotyping and mapping assay of single-nucleotide polymorphisms in CYP3A5 using
      DNA-binding zinc(II) complexes.
AB  - OBJECTIVE: It is clinically important to detect the single-nucleotide
      polymorphism (SNP) of CYP3A53 (6986A>G) associated with enzymatic activity for
      drug metabolism. The aim of this study was to establish an accurate strategy for
      SNP screening. DESIGN AND METHODS: Polyacrylamide gel electrophoresis (PAGE)
      using zinc(II) complexes were applied for SNP detection. Genomic analyses of 19
      healthy subjects were conducted by using both Zn(2+)-Phos-tag-PAGE and Zn(2+)
      cyclen-PAGE methodologies. RESULTS: Zn(2+)-Phos-tag PAGE permitted identification
      of the following allele genotypes: the A/A homozygote (CYP3A51/1) in 3
      individuals, the G/G homozygote (CYP3A53/3) in 14 individuals, and the A/G
      heterozygote (CYP3A51/3) in 2 individuals. Zn(2+)-cyclen PAGE demonstrated not
      only reproducibility of the genotyping but also existence of a novel heterozygous
      SNP (6929G>A) in the subject with CYP3A51/1. CONCLUSION: We demonstrated reliable
      SNP genotyping and mapping in CYP3A5 using the combination method of Zn(2+)-Phos
      tag PAGE and Zn(2+)-cyclen PAGE.

PMID- 19769956
TI  - Twenty-four-hour profiles of urinary excretion of calcium, magnesium, phosphorus,
      urea, and creatinine in healthy prepubertal boys.
AB  - OBJECTIVES: Available data on 24-h urinary solute excretion in healthy children
      are sparse. We thus documented the daily and overnight variations of urinary
      electrolytes (calcium, magnesium, and phosphorus), urea, and creatinine in
      prepubertal (Tanner stage I) boys. DESIGN AND METHODS: Nine voluntary healthy
      prepubertal boys aged 10.8+/-0.11 years participated in this study.
      Concentrations of variables were quantified in daytime samples (collected between
      07:00 h+/-30 min and 21:00 h+/-30 min) and nighttime samples (collected between
      21:00 h+/-30 min and 07:00 h+/-30 min) in spring, during a period of 24-h every 3
      h. RESULTS: Significant differences were found between daytime and nighttime
      excretion of calcium (p<0.05), magnesium (p<0.001), phosphorus (p<0.01), and urea
      (p<0.05), with high concentrations during the night. The 24-h solute/creatinine
      ratio was 0.072+/-0.008 mg/mg for calcium, 0.069+/-0.008 mg/mg for magnesium,
      0.698+/-0.070 mg/mg for phosphorus, and 0.017+/-0.001 g/mg for urea.
      Statistically significant correlation analyses showed that urea and creatinine
      were positively associated with body mass index (BMI) (R=0.790, p=0.0113 for
      urea; R=0.889, p=<0.0013 for creatinine) and weight (R=0.717, p=0.0297 for urea;
      R=0.978, p=<0.001 for creatinine). The other urinary variables were independent
      of BMI and body mass. CONCLUSION: These data are of interest for the diagnosis of
      certain renal disease in prepubertal children.

PMID- 19769957
TI  - The role of integrin alpha8beta1 in fetal lung morphogenesis and injury.
AB  - Prenatal inflammation prevents normal lung morphogenesis and leads to
      bronchopulmonary dysplasia (BPD), a common complication of preterm birth. We
      previously demonstrated in a bacterial endotoxin mouse model of BPD that
      disrupting fibronectin localization in the fetal lung mesenchyme causes arrested
      saccular airway branching. In this study we show that expression of the
      fibronectin receptor, integrin alpha8beta1 is decreased in the lung mesenchyme in
      the same inflammation model suggesting it is required for normal lung
      development. We verified a role for integrin alpha8beta1 in lung development
      using integrin alpha8-null mice, which develop fusion of the medial and caudal
      lobes as well as abnormalities in airway division. We further show in vivo and in
      vitro that alpha8-null fetal lung mesenchymal cells fail to form stable adhesions
      and have increased migration. Thus we propose that integrin alpha8beta1 plays a
      critical role in lung morphogenesis by regulating mesenchymal cell adhesion and
      migration. Furthermore, our data suggest that disruption of the interactions
      between extracellular matrix and integrin alpha8beta1 may contribute to the
      pathogenesis of BPD.

PMID- 19769959
TI  - Expression and requirement of T-box transcription factors Tbx2 and Tbx3 during
      secondary palate development in the mouse.
AB  - Formation of the mammalian secondary palate is a highly regulated and complex
      process. Impairment of the underlying cellular and molecular programs often
      results in cleft palate, a common birth defect in mammals. Here we report that
      Tbx2 and Tbx3, two closely related genes encoding T-box transcription factors,
      are expressed in the mesenchyme of the mouse palatal structures during
      development. Mice homozygous mutant for Tbx2 and mice double heterozygous for
      Tbx2 and Tbx3 exhibit a cleft palate phenotype arguing for an important
      contribution of Tbx2 and Tbx3 to palatogenesis. In Tbx2-deficient embryos, the
      bilateral primordial palatal shelves form but are smaller and retarded in the
      outgrowth process. They do not make contact but retain the potential to fuse.
      Development of other craniofacial structures appears normal, suggesting that
      impaired palate formation in Tbx2-mutant mice is caused by a primary defect in
      the palatal shelf mesenchyme. This is further supported by increased cell
      proliferation and apoptosis accompanied by increased expression of Bmp4 and
      CyclinD1 in Tbx2-deficient palatal shelves. Hence, Tbx2 and Tbx3 function
      overlappingly to control growth of the palatal shelf mesenchyme.

PMID- 19769958
TI  - Absence of heartbeat in the Xenopus tropicalis mutation muzak is caused by a
      nonsense mutation in cardiac myosin myh6.
AB  - Mechanisms coupling heart function and cardiac morphogenesis can be accessed in
      lower vertebrate embryos that can survive to swimming tadpole stages on diffused
      oxygen. Forward genetic screens in Xenopus tropicalis have identified more than
      80 mutations affecting diverse developmental processes, including cardiac
      morphogenesis and function. In the first positional cloning of a mutation in X.
      tropicalis, we show that non-contractile hearts in muzak (muz) embryos are caused
      by a premature stop codon in the cardiac myosin heavy chain gene myh6. The
      mutation deletes the coiled-coil domain responsible for polymerization into thick
      filaments, severely disrupting the cardiomyocyte cytoskeleton. Despite the lack
      of contractile activity and absence of a major structural protein, early stages
      of cardiac morphogenesis including looping and chamber formation are grossly
      normal. Muz hearts subsequently develop dilated chambers with compressed
      endocardium and fail to form identifiable cardiac valves and trabeculae.

PMID- 19769960
TI  - Eugenol protects nicotine-induced superoxide mediated oxidative damage in murine
      peritoneal macrophages in vitro.
AB  - The present work is aimed at evaluating the protective effect of eugenol against
      in vitro nicotine-induced toxicity in murine peritoneal macrophages, compared
      with N-acetylcysteine. Eugenol was isolated from Ocimum gratissimum and
      characterized by HPLC, FTIR, (1)H NMR. To establish most effective protective
      support, we used five different concentrations of eugenol (1, 5, 10, 15, and
      20microg/ml) and N-acetylcysteine (0.25, 0.5, 1.0, 2.0, and 5.0microg/ml) against
      10mM nicotine in mice peritoneal macrophages. A dose-dependent protective effect
      was observed with all doses of eugenol and N-acetylcysteine, as evidenced by
      decreased level of superoxide anion generation and malondialdehyde, and also
      increased level of reduced glutathione, and superoxide dismutase activity.
      Moreover, maximum protection was observed at the concentration of 15.0microg/ml
      eugenol (0.09nM) and 1.0microg/ml N-acetylcysteine (0.006nM). Further, eugenol
      (15.0microg/ml) and N-acetylcysteine (1.0microg/ml) were tested against nicotine
      (10mM) toxicity by analyzing the radical generation, lipid, protein, DNA damage,
      and endogenous antioxidant status. There was a significant increase in the level
      of radical generation, NADPH oxidase and myeloperoxidase activity, lipid,
      protein, DNA damage and oxidized glutathione level in nicotine-treated group,
      which were significantly reduced by eugenol and N-acetylcysteine supplementation.
      Antioxidant status was significantly depleted in the nicotine-treated group,
      which was effectively restored by eugenol and N-acetylcysteine supplementation.
      The protection by eugenol against nicotine toxicity was merely equal effective to
      that of N-acetylcysteine. These findings suggest the potential use and benefit of
      eugenol isolated from O. gratissimum as a modulator of nicotine-induced cellular
      damage and it may be used as an immunomodulatory drug against nicotine toxicity.

PMID- 19769961
TI  - Toll-like receptor and chemokine receptor expression in HIV-infected T lymphocyte
      subsets.
AB  - In the present investigation, flow cytometric techniques were utilized to
      evaluate 100 cases of HIV and 20 normal controls for CXCR4, CCR5, and TLR4
      expression in CD4-positive T cells, CD8-positive T cells, regulatory T cells, and
      Th17 cells, and fluorescence intensity values were determined. TLR4 was expressed
      by CD4+ T cells and CD8+ T cells in 97 cases, by regulatory T cells in 88 of 95
      cases, and by Th17 cells in 93 of 95 cases, while it remained negative in all 20
      normal controls. These data indicate that TLR4 upregulation is not limited to
      gram-negative bacterial infection nor is expression limited to myeloid cells.
      Upregulation of TLR4 in HIV patients may either be directly or indirectly related
      to the presence of the virus. CXCR4 was positively expressed by CD4+ T cells in
      96 HIV cases, CD8+ T cells in 95, regulatory T cells in 89 of 95 cases evaluated,
      and Th17 cells in all 92 cases evaluated, while expression remained negative in
      the majority of normal controls. CCR5 was positively expressed by CD4+ and CD8+ T
      cells in all 100 HIV cases and by regulatory T cells in 89 of 95 cases evaluated,
      while expression was negative in most CD4+ and regulatory T cells of normal
      controls. Statistically significant differences were detected when TLR4
      expression by CD4+ and CD8+ T cells was compared to stage of disease. TLR4
      expression decreased as infection progressed from acute phase to AIDS. In
      addition, expression of TLR4 by all T cell subsets was slightly decreased in
      patients receiving HAART therapy. Results also reveal a positive correlation
      between CXCR4, CCR5, and TLR4 expression indicating that TLR4 expression and
      chemokine expression pathways are linked.

PMID- 19769962
TI  - ADAM12 localizes with c-Src to actin-rich structures at the cell periphery and
      regulates Src kinase activity.
AB  - ADAM12 is an active metalloprotease playing an important role in tumour
      progression. Human ADAM12 exists in two splice variants: a long transmembrane
      form, ADAM12-L, and a secreted form, ADAM12-S. The subcellular localization of
      ADAM12-L is tightly regulated and involves intracellular interaction partners and
      signalling proteins. We demonstrate here a c-Src-dependent redistribution of
      ADAM12-L from perinuclear areas to actin-rich Src-positive structures at the cell
      periphery, and identified two separate c-Src binding sites in the cytoplasmic
      tail of ADAM12-L that interact with the SH3 domain of c-Src with different
      binding affinities. The association between ADAM12-L and c-Src is transient, but
      greatly stabilized when the c-Src kinase activity is disrupted. In agreement with
      this observation, kinase-active forms of c-Src induce ADAM12-L tyrosine
      phosphorylation. Interestingly, ADAM12-L was also found to enhance Src kinase
      activity in response to external signals, such as integrin engagement. Thus, we
      suggest that activated c-Src binds, phosphorylates, and redistributes ADAM12-L to
      specific sites at the cell periphery, which may in turn promote signalling
      mechanisms regulating cellular processes with importance in cancer.

PMID- 19769963
TI  - Dissecting coronary angiogenesis: 3D co-culture of cardiomyocytes with
      endothelial or mesenchymal cells.
AB  - In embryogenesis, coronary blood vessels are formed by vasculogenesis from
      epicardium-derived progenitors. Subsequently, growing or regenerating myocardium
      increases its vasculature by angiogenesis, forming new vessels from the pre
      existing ones. Recently, cell therapies for myocardium ischemia that used
      different protocols have given promising results, using either extra-cardiac
      blood vessel cell progenitors or stimulating the cardiac angiogenesis. We have
      questioned whether cardiomyocytes could sustain both vasculogenesis and
      angiogenesis. We used a 3D culture model of tissue-like spheroids in co-cultures
      of cardiomyocytes supplemented either with endothelial cells or with bone marrow
      derived mesenchymal stroma cells. Murine foetal cardiomyocytes introduced into
      non-adherent U-wells formed 3D contractile structures. They were coupled by gap
      junctions. Cardiomyocytes segregated inside the 3D structure into clumps
      separated by connective tissue septa, rich in fibronectin. Three vascular
      endothelial growth factor isoforms were produced (VEGF 120, 164 and 188). When co
      cultured with human umbilical cord endothelial cells, vascular structures were
      produced in fibronectin-rich external layer and in radial septa, followed by
      angiogenic sprouting into the cardiomyocyte microtissue. Presence of vascular
      structures led to the maintenance of long-term survival and contractile capacity
      of cardiac microtissues. Conversely, bone marrow mesenchymal cells formed
      isolated cell aggregates, which progressively expressed the endothelial markers
      von Willebrand's antigen and CD31. They proceeded to typical vasculogenesis
      forming new blood vessels organised in radial pattern. Our results indicate that
      the in vitro 3D model of cardiomyocyte spheroids provides the two basic elements
      for formation of new blood vessels: fibronectin and VEGF. Within the myocardial
      environment, endothelial and mesenchymal cells can proceed to formation of new
      blood vessels either through angiogenesis or vasculogenesis, respectively.

PMID- 19769964
TI  - LRRK2 enhances oxidative stress-induced neurotoxicity via its kinase activity.
AB  - LRRK2 is an autosomal dominant gene whose mutations cause familial Parkinson's
      disease (PD). The LRRK2 protein contains a functional kinase and a GTPase domain.
      PD phenotypes caused by LRRK2 mutations are similar to those of idiopathic PD,
      implying that LRRK2 is an important participant in PD pathogenesis. Of LRRK2's PD
      specific mutations, the G2019S is the most frequently observed one. Its over
      expression is known to increase kinase activity and neurotoxicity compared to
      wild type (WT) LRRK2. Here, using a simple colorimetric cell viability assay, we
      analyzed LRRK2's neurotoxicity in dopaminergic SN4741 cells following treatment
      with hydrogen peroxide. When WT, G2019S, or empty vector was expressed in SN4741
      cells, cell death was modestly and significantly increased in the order of
      G2019S>WT>vector. When these transfected cells were treated with hydrogen
      peroxide to mimic oxidative stress, cellular neurotoxicity was enhanced in the
      same order (i.e. G2019S>WT>vector). Moreover, incubation of SN4741 cells with
      conditioned medium from cells expressing G2019S and subjected to hydrogen
      peroxide treatment exhibited 10-15% more cell death than conditioned medium from
      cells transfected with vector or WT, suggesting that G2019S-expressing cells
      secrete a factor(s) affecting viability of neighboring cells. The kinase domain
      was mapped to be responsible for oxidative stress-induced neurotoxicity. In
      addition, over-expression of WT and G2019S LRRK2 lead to a weak, but significant,
      increase in intracellular reactive oxygen species (ROS) in the order of G2019S>WT
      as measured by DCFH-DA assay in both the presence and absence of H(2)O(2)
      treatment. Furthermore, in G2019S-expressing cells, co-expression of the anti
      oxidant protein DJ-1 or ERK inhibitor treatment restored survival rate to a level
      similar to that of cells transfected with control vector under H(2)O(2)
      treatment. Taken together, our data suggest that the LRRK2 kinase domain
      increases the generation of ROS and causes enhanced neurotoxicity under H(2)O(2)
      treatment, which can be at least partially rescued by DJ-1 or the ERK inhibitor.

PMID- 19769965
TI  - CREG inhibits migration of human vascular smooth muscle cells by mediating IGF-II
      endocytosis.
AB  - We previously determined that the cellular repressor of E1A-stimulated genes,
      (CREG) plays a role in the maintenance of the mature phenotype of vascular smooth
      muscle cells (SMCs). This study aimed to identify the role of CREG in modulating
      the migration of SMCs. Recombinant virus-mediated CREG expression inhibited the
      cellular migration of cultured SMCs associated with down-regulated activity of
      matrix metalloproteinase-9 (MMP-9). In contrast, CREG knockdown via the
      retroviral transfer of short hairpin RNAs promoted cellular migration. Enzyme
      linked immunosorbent assay and endocytosis analysis revealed that CREG knockdown
      attenuated the internalization and increased secretion of insulin-like growth
      factor (IGF)-II. Western blot analysis demonstrated that both phosphoinositide 3
      kinase (PI3K) and phosphatase Akt were enhanced in CREG knockdown SMCs.
      Furthermore, the effect of CREG knockdown on SMC migration was abrogated in a
      dose-dependent manner by the addition of either IGF-II neutralizing antibody or
      the PI3K inhibitor, LY294002. These results indicate that the CREG knockdown
      mediated increase in IGF-II secretion promoted cellular migration in SMCs via the
      PI3K/Akt signal pathway. Additionally, blockage of IGF-II binding to the mannose
      6-phosphate/IGF-II receptor (M6P/IGF2R) by IGF2R antibody or recombinant IGF2R
      fragment attenuated the endocytosis of IGF-II in cells overexpressing CREG. This
      indicates that M6P/IGF2R is involved in the regulation of CREG-mediated IGF-II
      endocytosis. In summary, these data demonstrate for the first time that CREG
      plays a critical role in the inhibition of SMC migration, as well as maintaining
      SMCs in a mature phenotype. These results may provide a new therapeutic target
      for vascular disease associated with neointimal hyperplasia.

PMID- 19769967
TI  - Current applications and future perspectives of artificial nerve conduits.
AB  - Artificial nerve guide conduits have the advantage over autografts in terms of
      their availability and ease of fabrication. However, clinical outcomes associated
      with the use of artificial nerve conduits are often inferior to that of
      autografts, particularly over long lesion gaps. There have been significant
      advances in the designs of artificial nerve conduits over the years. In terms of
      materials selection and design, a wide variety of new synthetic polymers and
      biopolymers have been evaluated. The inclusion of nerve conduit lumen fillers has
      also been demonstrated as essential to enable nerve regeneration across large
      defect gaps. These lumen filler designs have involved the integration of physical
      cues for contact guidance and biochemical signals to control cellular function
      and differentiation. Novel conduit architectural designs using porous and fibrous
      substrates have also been developed. This review highlights the recent advances
      in synthetic nerve guide designs for peripheral nerve regeneration, and the in
      vivo applicability and future prospects of these nerve guide conduits.

PMID- 19769968
TI  - Echinococcus multilocularis: two-dimensional Western blotting method for the
      identification and expression analysis of immunogenic proteins in infected dogs.
AB  - Domesticated dogs are an important potential source of Echinococcus
      multilocularis infection in humans; therefore, new molecular approaches for the
      prevention of the parasite infection in dogs need to be developed. Here, we
      identified and characterized an immunogenic protein of the parasite by using a
      proteome-based approach. The total protein extracted from protoscoleces was
      subjected to two-dimensional Western blotting with sera from dogs experimentally
      infected with E. multilocularis. Two protein spots showed major reactivity to the
      sera from infected dogs. The N-terminal amino acid sequences of these spots were
      identical to the deduced amino acid sequence of the product of the putative hsp20
      gene. RT-PCR and Western blot analyses revealed that the putative hsp20 gene and
      its products were expressed in almost all stages of the parasite life cycle.
      Furthermore, recombinant hsp20 showed specific reactivity to the sera from
      infected dogs, suggesting that this molecule may facilitate the development of a
      practical vaccine.

PMID- 19769966
TI  - The cell senescence inducing gene product MORF4 is regulated by degradation via
      the ubiquitin/proteasome pathway.
AB  - After undergoing several rounds of divisions normal human fibroblasts enter a
      terminally non-dividing state referred to as cellular or replicative senescence.
      We cloned MORF4 (mortality factor on human chromosome 4), as a cellular
      senescence inducing gene that caused immortal cells assigned to complementation
      group B for indefinite division to stop dividing. To facilitate analyses of this
      gene, which is toxic to cells at low levels, we obtained stable clones of HeLa
      cells expressing a tetracycline-induced MORF4 construct that could be induced by
      doxycycline in a dose-dependent manner. MORF4 induction resulted in reduced
      colony formation after 14 days of culture, as previously observed. We determined
      that MORF4 protein was unstable and that addition of the proteasome inhibitor
      MG132 resulted in the accumulation of the protein. Following removal of MG132 the
      protein was rapidly degraded. Subcellular fractionation following MG132 treatment
      demonstrated that the protein accumulates primarily in the cytoplasm with some
      amounts present in the nucleus. It is therefore possible that MORF4 protein,
      which escapes degradation in the cytoplasm, is transported to the nucleus where
      it is functional. The results suggest that levels of MORF4 in cells must be
      tightly controlled and one mechanism involves stability of the protein.

PMID- 19769969
TI  - Identification and differentiation of Fasciola hepatica and Fasciola gigantica
      using a simple PCR-restriction enzyme method.
AB  - Accurate morphological differentiation between the liver fluke species Fasciola
      hepatica and Fasciola gigantica is difficult. We evaluated PCR-restriction enzyme
      profiles of internal transcribed spacer 1 (ITS1) that could aid in their
      identification. Fifty F. hepatica and 30 F. gigantica specimens were collected
      from different hosts in three provinces of Iran. For DNA extraction, we crushed
      fragments of the worms between two glass slides as a new method to break down the
      cells. DNA from the crushed materials was then extracted with a conventional
      phenol-chloroform method and with the newly developed technique, commercial FTA
      cards. A primer pair was selected to amplify a 463-bp region of the ITS1
      sequence. After sequencing 14 samples and in silico analysis, cutting sites of
      all known enzymes were predicted and TasI was selected as the enzyme that yielded
      the most informative profile. Crushing produced enough DNA for PCR amplification
      with both the phenol-chloroform and commercial FTA card method. The DNA extracted
      from all samples was successfully amplified and yielded a single sharp band of
      the expected size. Digestion of PCR products with TasI allowed us to distinguish
      the two species. In all samples, molecular identification was consistent with
      morphological identification. Our PCR-restriction enzyme profile is a simple,
      rapid and reliable method for differentiating F. hepatica and F. gigantica, and
      can be used for diagnostic and epidemiological purposes.

PMID- 19769970
TI  - Leishmania major lipophosphoglycan: discrepancy in Toll-like receptor signaling.
AB  - Lipophosphoglycan (LPG) is structurally characterized by a series of
      phosphoglycan repeat units. Cellular LPG, isolated from promastigotes, has a very
      similar structure to culture supernatant LPG, but differs in the average number
      of phosphorylated oligosaccharide repeat units and in glycan composition.
      Comparison of these LPGs with capillary electrophoresis and immunoblotting
      indicate that these molecules are highly conserved structurally and composed of
      galactosylated Gal-Man repeats but their size and molecular weight are very
      different which is due to glycan portion. There are 30 and 20 repeat units in
      sLPG and mLPG, respectively. Both LPGs induced nitric oxide in macrophages cell
      line while sLPG had the higher stimulatory effect. In the presence of anti-TLR2
      nitric oxide stimulated by LPG was reduced to control levels. In addition, in the
      presence of anti-TLR4, nitric oxide stimulated by LPGs was not affected. We
      propose that lipophosphoglycan induces nitric oxide production via TLR2 signaling
      pathway.

PMID- 19769971
TI  - Metabolic systems biology.
AB  - The first full genome sequences were established in the mid-1990s. Shortly
      thereafter, genome-scale metabolic network reconstructions appeared. Since that
      time, we have witnessed an exponential growth in their number and uses. Here I
      discuss, from a personal point of view, four topics: (1) the placement of
      metabolic systems biology in the context of broader scientific developments, (2)
      its foundational concepts, (3) some of its current uses, and (4) some of the
      expected future developments in the field.

PMID- 19769973
TI  - Hepatitis C virus core protein subverts the antiviral activities of human Kupffer
      cells.
AB  - BACKGROUND & AIMS: Kupffer cells (KC) are important innate immune cells of the
      liver, functioning as scavenging sinusoidal phagocytes and transducers of pattern
      recognition signals, including those of toll-like receptors (TLRs). The hepatitis
      C virus core protein (HCVc) engages TLR2 on peripheral blood monocytes and
      induces production of multiple inflammatory cytokines. We examined the effects of
      HCVc on human primary KC functions. METHODS: KC were isolated from living donor
      allografts and stimulated with HCVc and/or ligands for TLRs. KC were examined for
      production of cytokines, expression of programmed death-ligand 1 (PD-L1),
      secretion of type 1 interferons (IFNs), and expression of the apoptosis-inducing
      protein tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL).
      RESULTS: HCVc acts as a ligand for TLR2 on human KC, inducing them to secrete
      interleukin (IL)-1beta, TNF-alpha, and IL-10 and up-regulate cell surface PD-L1.
      HCVc blocked TLR3-mediated secretion of IFN-alpha, IFN-beta, and cell surface
      expression of the cytotoxic molecule TRAIL. Inhibition of phosphoinositide 3
      kinase with LY294002 blocked the up-regulation of PD-L1 by TLR ligands and the
      TLR3-specific induction of TRAIL and type 1 IFNs. CONCLUSIONS: KC are
      intravascular macrophages that are continuously exposed to, and tolerant of,
      bacterial TLR ligands, which are delivered via the portal circulation. By
      mimicking a bacterial TLR2 ligand and effectively blocking the TLR3-mediated,
      double-stranded RNA-induced antiviral response, HCVc might appear to exploit this
      unique aspect of immunity in the liver.

PMID- 19769978
TI  - Sensitization enhances acquisition of cocaine self-administration in female rats:
      estradiol further enhances cocaine intake after acquisition.
AB  - Cocaine self-administration in rodents has been used widely as a preclinical
      model of cocaine use in humans. In laboratory animals, estradiol enhances
      behavioral sensitization to cocaine and the acquisition of cocaine self
      administration in female rats. The rewarding effect of cocaine has been shown to
      be enhanced following behavioral sensitization in male rats. This experiment
      examined whether behavioral sensitization to cocaine would promote cocaine-taking
      behavior in female rats, and whether estradiol could further modulate cocaine
      taking behavior in cocaine-sensitized rats. Ovariectomized female rats were
      pretreated with either cocaine or saline for 4 days per week for 3 weeks. Self
      administration sessions started 2 weeks after the last dose of drug. Female
      Sprague-Dawley rats received either estradiol or oil 30 min prior to the start of
      each session and self-administration was carried out 5 days per week for 4 weeks.
      The dose of cocaine self-administered each week was as follows (in
      mg/kg/infusion): week 1, 0.1; week 2, 0.1; week 3, 0.15; and week 4, 0.4. The
      rats that received cocaine pretreatment took fewer days to acquire cocaine self
      administration and took more cocaine than rats that received saline pretreatment.
      Estradiol enhanced cocaine intake during the last six self-administration
      sessions after acquisition but did not affect acquisition of self-administration
      at the lowest doses of cocaine used. In conclusion, cocaine sensitization
      promotes the acquisition of cocaine self-administration in female rats.
      Furthermore, prior cocaine experience is more powerful than estradiol at
      enhancing acquisition, while estradiol enhances intake of cocaine after
      acquisition of self-administration.

PMID- 19769979
TI  - Sexual incentive motivation in male rats requires both androgens and estrogens.
AB  - In Experiment 1 castrated male rats were implanted with a Silastic capsule
      containing either E or cholesterol (CHOL) 35 days after castration. They were
      then tested for sexual incentive motivation and copulatory behaviors every 5th
      day for 3 weeks. None of the treatments affected sexual incentive motivation.
      After the last test, all subjects were implanted with DHT-containing Silastic
      capsules, and tests continued for another 3 weeks. While E+DHT enhanced sexual
      incentive motivation and copulatory behavior, DHT alone failed to do so. In
      Experiment 2 the aromatase inhibitor fadrozole (F) was combined with testosterone
      (T). T restored all behaviors to the level seen in intact rats, and F
      significantly reduced these effects. In fact, T+F was not different from DHT. T
      and DHT restored the weight of the prostate and seminal vesicles to levels close
      to those of intact rats. In Experiment 3 a lower dose of E was employed. Also
      this dose of E failed to affect sexual incentive motivation while E+DHT restored
      it to the level of intact animals. Castration enhanced the serum concentrations
      of LH and FSH. E alone caused a marked reduction, and E+DHT brought both
      gonadotropins back to the level of intact animals. It was concluded that the
      doses of E and DHT employed in these experiments were within or close to the
      physiological range, and that such doses of E completely fail to enhance sexual
      incentive motivation in castrated animals. DHT has small or no effects. It
      appears that sexual incentive motivation and copulation require simultaneous
      stimulation of androgen and estrogen receptors.

PMID- 19769980
TI  - Deadly venom of Asobara japonica parasitoid needs ovarian antidote to regulate
      host physiology.
AB  - Asobara japonica (Braconidae) is an endophagous parasitoid developing in
      Drosophila larvae. The present study shows that A. japonica was never
      encapsulated in Drosophila melanogaster, and that it caused an overall inhibition
      of the host encapsulation reaction since injected foreign bodies were never
      encapsulated in parasitized hosts. Both the number of circulating hemocytes and
      the phenoloxidase activity decreased in parasitized larvae, and the hematopoietic
      organ appeared highly disrupted. We also found that A. japonica venom secretions
      had atypical effects on hosts compared to other braconid wasps. A. japonica venom
      secretions induced permanent paralysis followed by death of D. melanogaster
      larvae, whether injected by the female wasp during an interrupted oviposition, or
      manually injected into unparasitized larvae. More remarkably, these effects could
      be reversed by injection of ovarian extracts from female wasps. This is the first
      report that the venom of an endophagous braconid parasitoid can have a deadly
      effect on hosts, and moreover, that ovarian extracts can act as an antidote to
      reverse the effects of the wasp's venom. These results also demonstrate that A.
      japonica secretions from both venom gland and ovary are required to regulate
      synergistically the host physiology for the success of the parasitoid.

PMID- 19769977
TI  - Illicit anabolic-androgenic steroid use.
AB  - The anabolic-androgenic steroids (AAS) are a family of hormones that includes
      testosterone and its derivatives. These substances have been used by elite
      athletes since the 1950s, but they did not become widespread drugs of abuse in
      the general population until the 1980s. Thus, knowledge of the medical and
      behavioral effects of illicit AAS use is still evolving. Surveys suggest that
      many millions of boys and men, primarily in Western countries, have abused AAS to
      enhance athletic performance or personal appearance. AAS use among girls and
      women is much less common. Taken in supraphysiologic doses, AAS show various long
      term adverse medical effects, especially cardiovascular toxicity. Behavioral
      effects of AAS include hypomanic or manic symptoms, sometimes accompanied by
      aggression or violence, which usually occur while taking AAS, and depressive
      symptoms occurring during AAS withdrawal. However, these symptoms are
      idiosyncratic and afflict only a minority of illicit users; the mechanism of
      these idiosyncratic responses remains unclear. AAS users may also ingest a range
      of other illicit drugs, including both "body image" drugs to enhance physical
      appearance or performance, and classical drugs of abuse. In particular, AAS users
      appear particularly prone to opioid use. There may well be a biological basis for
      this association, since both human and animal data suggest that AAS and opioids
      may share similar brain mechanisms. Finally, AAS may cause a dependence syndrome
      in a substantial minority of users. AAS dependence may pose a growing public
      health problem in future years but remains little studied.

PMID- 19769981
TI  - Impact of a juvenile hormone analogue on the anatomy and the frontal gland
      secretion of Prorhinotermes simplex (Isoptera: Rhinotermitidae).
AB  - In termites, juvenile hormone plays a key role in soldier differentiation. To
      better understand the evolutionary origin of the soldiers, we studied the
      external and inner morphology of pseudergate-soldier intercastes and neotenic
      soldier intercastes formed artificially by the application of juvenile hormone
      analogue in Prorhinotermes simplex. A majority of these intercastes had a soldier
      phenotype, whereas the inner anatomy had an intermediary form between two castes
      or a form specific to intercastes. Our experiments showed that traits of
      neotenics and soldiers can be shared by the same individuals, although such
      individuals do not exist naturally in P. simplex, and they have not been reported
      in other species but in some Termopsidae. Our results reinforce the hypothesis
      that soldiers may have emerged from soldier neotenics during the evolution of
      termites.

PMID- 19769983
TI  - Angiotensin II type 1 receptor-associated protein prevents vascular smooth muscle
      cell senescence via inactivation of calcineurin/nuclear factor of activated T
      cells pathway.
AB  - Emerging new research suggests that the functions of the angiotensin (Ang) II
      type 1 (AT(1)) receptor are regulated in a complex manner. AT(1) receptor
      associated protein (ATRAP) has been reported to reduce AT(1) receptor signaling
      with enhancement of AT(1) receptor internalization and to regulate the
      calcineurin/nuclear factor of activated T cells (NFAT) pathway. We examined the
      possibility that ATRAP could attenuate AT(1) receptor-mediated vascular
      senescence via inactivation with the calcineurin/NFAT pathway. Ang II stimulation
      significantly increased senescence-associated beta-galactosidase (SA-beta-gal)
      stained cells, oxidative stress, and expression of p53 and p21 in wild-type (WT)
      vascular smooth muscle cells (VSMC). Moreover, in WT VSMC, Ang II stimulation
      enhanced NFAT transcriptional activity, which was prevented by CAML-siRNA
      treatment. NFAT-siRNA treatment attenuated Ang-II-increased SA-beta-gal activity
      and p53 and p21 expression. Treatment with a calcineurin activity inhibitor,
      cyclosporin A, reduced Ang-II-induced NFAT transcriptional activity and senescent
      VSMC. In contrast, VSMC prepared from ATRAP transgenic (ATRAP-Tg) mice exhibited
      attenuation of Ang-II-induced SA-beta-gal activity, oxidative stress, NFAT
      transcriptional activity, and expression of p53 and p21. Moreover, ATRAP-Tg VSMC
      showed a more reduction of Ang-II-induced NFAT transcriptional activity by CAML
      siRNA treatment than WT VSMC. Furthermore, we demonstrated that in ATRAP-Tg VSMC,
      NFAT activity and senescent cells induced by ultraviolet irradiation were
      decreased compared with those in WT VSMC. Treatment with an AT(1) receptor
      blocker, valsartan, blocked these senescent cells but did not change NFAT
      activity in both cells. These results suggest that ATRAP negatively regulates
      VSMC senescence by reducing AT(1) receptor signaling, and that ATRAP-mediated
      inactivation of the calcineurin/NFAT pathway could be at least partly involved in
      prevention of VSMC senescence, irrespective of AT(1) receptor blockade in some
      conditions.

PMID- 19769984
TI  - The on-off switch in regulated myosins: different triggers but related
      mechanisms.
AB  - In regulated myosin, motor and enzymatic activities are toggled between the on
      state and off-state by a switch located on its lever arm domain, here called the
      regulatory domain (RD). This region consists of a long alpha-helical "heavy
      chain" stabilized by a "regulatory" light chain (RLC) and an "essential" light
      chain (ELC). The on-state is activated by phosphorylation of the RLC of
      vertebrate smooth muscle RD or by direct binding of Ca(2+) to the ELC of
      molluscan RD. Crystal structures are available only for the molluscan RD. To
      understand in more detail the pathway between the on-state and the off-state, we
      have now also determined the crystal structure of a molluscan (scallop) RD in the
      absence of Ca(2+). Our results indicate that loss of Ca(2+) abolishes most of the
      interactions between the light chains and may increase the flexibility of the RD
      heavy chain. We propose that disruption of critical links with the C-lobe of the
      RLC is the key event initiating the off-state in both smooth muscle myosins and
      molluscan myosins.

PMID- 19769985
TI  - Crystal structure of HypA, a nickel-binding metallochaperone for [NiFe]
      hydrogenase maturation.
AB  - HypA is one of the auxiliary proteins involved in the maturation of [NiFe]
      hydrogenases. By an unknown mechanism, HypA functions as a metallochaperone in
      the insertion of the Ni atom into hydrogenases. We have determined the crystal
      structures of HypA from Thermococcus kodakaraensis KOD1 in both monomeric and
      dimeric states. The structure of the HypA monomer consists of Ni- and Zn-binding
      domains. The relative arrangement of the two metal-binding domains has been shown
      to be associated with local conformations of the conserved Ni-binding motif,
      suggesting a communication between the Ni- and Zn-binding sites. The HypA dimer
      has been shown to be stabilized by unexpected domain swapping through archaea
      specific linker helices. In addition, the hexameric structure of HypA is formed
      in the crystal packing. Several hydrogen bonds and hydrophobic interactions
      stabilize the hexamer interface. These findings suggest the functional diversity
      of HypA proteins.

PMID- 19769987
TI  - CARM1 but not its enzymatic activity is required for transcriptional coactivation
      of NF-kappaB-dependent gene expression.
AB  - Coactivator-associated arginine methyltransferase 1 (CARM1) belongs to the
      protein arginine methyltransferase family. It was reported to methylate histone
      as well as non-histone proteins and thus to be involved in transcriptional
      activation and mRNA degradation/stability. Here we report the genetic
      complementation of carm1-/- cells with wild-type CARM1 or an enzymatic inactive
      mutant of CARM1 to investigate the requirement of CARM1 and its enzymatic
      activity for nuclear factor kappaB (NF-kappaB)-dependent gene expression. Using
      custom microarray and quantitative reverse transcription PCR, we could define a
      subset of NF-kappaB target genes that required CARM1 for their proper expression.
      Although several tumor necrosis factor-alpha- and phorbol-12-myristate-13
      acetate/ionomycin-induced NF-kappaB target genes are CARM1 dependent, CARM1
      enzymatic activity was dispensable for gene expression. Interestingly, CARM1 was
      not required for the stimulus-dependent recruitment of RelA/p65 to chromatin,
      suggesting that CARM1 is rather contributing in protein complex stabilization.
      Together, our results confirm the importance of CARM1 as transcriptional cofactor
      without the involvement of its catalytic activity.

PMID- 19769982
TI  - Alterations in mitochondrial function as a harbinger of cardiomyopathy: lessons
      from the dystrophic heart.
AB  - While compelling evidence supports the central role of mitochondrial dysfunction
      in the pathogenesis of heart failure, there is comparatively less information
      available on mitochondrial alterations that occur prior to failure. Building on
      our recent work with the dystrophin-deficient mdx mouse heart, this review
      focuses on how early changes in mitochondrial functional phenotype occur prior to
      overt cardiomyopathy and may be a determinant for the development of adverse
      cardiac remodelling leading to failure. These include alterations in energy
      substrate utilization and signalling of cell death through increased permeability
      of mitochondrial membranes, which may result from abnormal calcium handling, and
      production of reactive oxygen species. Furthermore, we will discuss evidence
      supporting the notion that these alterations in the dystrophin-deficient heart
      may represent an early "subclinical" signature of a defective nitric oxide/cGMP
      signalling pathway, as well as the potential benefit of mitochondria-targeted
      therapies. While the mdx mouse is an animal model of Duchenne muscular dystrophy
      (DMD), changes in the structural integrity of dystrophin, the mutated
      cytoskeletal protein responsible for DMD, have also recently been implicated as a
      common mechanism for contractile dysfunction in heart failure. In fact,
      altogether our findings support a critical role for dystrophin in maintaining
      optimal coupling between metabolism and contraction in the heart.

PMID- 19769986
TI  - Lattice structure of cytoplasmic microtubules in a cultured Mammalian cell.
AB  - Tubulin can polymerize in two distinct arrangements: "B-lattices," in which the
      alpha-tubulins of one protofilament lie next to alpha-tubulins in the neighboring
      protofilaments, or the "A" configuration, where alpha-tubulins lie beside beta
      tubulins. Microtubules (MTs) in flagellar axonemes and those assembled from pure
      tubulin in vitro display only B-lattices, but recent work shows that A-lattices
      are found when tubulin co-polymerizes in vitro with an allele of end-binding
      protein 1 that lacks C-terminal sequences. This observation suggests that
      cytoplasmic MTs, which form in the presence of this "tip-associating protein,"
      may have A-lattices. To test this hypothesis, we have decorated interphase MTs in
      3T3 cells with monomeric motor domains from the kinesin-like protein Eg5. These
      MTs show only B-lattices, as confirmed by visual inspection of electron cryo
      tomograms and power spectra of single projection views, imaged at higher electron
      dose. This result is significant because 13 protofilament MTs with B-lattices
      must include a "seam," one lateral domain where adjacent dimers are in the A
      configuration. It follows that cytoplasmic MTs are not cylindrically symmetric;
      they have two distinct faces, which may influence the binding patterns of
      functionally significant MT-interacting proteins.

PMID- 19769988
TI  - Alternative to homo-oligomerisation: the creation of local symmetry in proteins
      by internal amplification.
AB  - The biologically active state of many proteins requires their prior homo
      oligomerisation. Such complexes are typically symmetrical, a feature that has
      been proposed to increase their stability and facilitate the evolution of
      allosteric regulation. We wished to examine the possibility that similar
      structures and properties could arise from genetic amplifications leading to
      internal symmetrical repeats. For this, we identified internal structural repeats
      in a nonredundant Protein Data Bank subset. While testing if repeats in proteins
      tend to be symmetrical, we found that about half of the large internal repeats
      are symmetrical, most frequently around a rotation axis of 180 degrees . These
      repeats were most likely created by genetic amplification processes because they
      show significant sequence similarity. Symmetrical repeats tend to have a fixed
      number of copies corresponding to their rotational symmetry order, that is, two
      for 180 degrees rotation axis, whereas asymmetrical repeats are in longer
      proteins and show copy number variability. When possible, we confirmed that
      proteins with symmetrical repeats folding as an n-mer have homologues lacking the
      repeat with a higher oligomerisation number corresponding to the rotation
      symmetry order of the repeat. Phylogenetic analyses of these protein families
      suggest that typically, but not always, symmetrical repeats arise in one single
      event from proteins that are homo-oligomers. These results suggest that
      oligomerisation and amplification of internal sequences can interplay in
      evolutionary terms because they result in functional analogues when the latter
      exhibit rotational symmetry.

PMID- 19769989
TI  - Translation of mRNAs from vesicular stomatitis virus and vaccinia virus is
      differentially blocked in cells with depletion of eIF4GI and/or eIF4GII.
AB  - Cytolytic viruses abrogate host protein synthesis to maximize the translation of
      their own mRNAs. In this study, we analyzed the eukaryotic initiation factor
      (eIF) 4G requirement for translation of vesicular stomatitis virus (VSV) and
      vaccinia virus (VV) mRNAs in HeLa cells using two different strategies: eIF4G
      depletion by small interfering RNAs or cleavage of eIF4G by expression of
      poliovirus 2A protease. Depletion of eIF4GI or eIF4GII moderately inhibits
      cellular protein synthesis, whereas silencing of both factors has only a slightly
      higher effect. Under these conditions, the extent of VSV protein synthesis is
      similar to that of nondepleted control cells, whereas VV expression is
      substantially reduced. Similar results were obtained when eIF4E was depleted. On
      the other hand, eIF4G cleavage by poliovirus 2A protease strongly inhibits
      translation of VV protein expression, whereas translation directed by VSV mRNAs
      is not abrogated, even though VSV mRNAs are capped. Therefore, the requirement
      for eIF4F activity is different for VV and VSV, suggesting that the molecular
      mechanism by which their mRNAs initiate their translation is also different.
      Consistent with these findings, eIF4GI does not colocalize with ribosomes in VSV
      infected cells, while eIF2alpha locates at perinuclear sites coincident with
      ribosomes.

PMID- 19769990
TI  - Transmission dynamics and underreporting of Kala-azar in the Indian state of
      Bihar.
AB  - "Kala-azar" (or Indian Visceral Leishmaniasis) is a vector-borne infectious
      disease affecting communities in tropical and subtropical areas of the world.
      Bihar, a state in India, has one of the highest prevalence and mortality reported
      levels of Kala-azar. Yet, the magnitude of the problem is difficult to assess
      because most cases are handled by private health providers who are not required
      to and do not report them to the Ministry of Health. The impact of underreporting
      using district-level reported incidence data from the state of Bihar is the main
      goal of this manuscript. We derive expressions for, and compute estimates of Kala
      azar's reproduction numbers, an indirect measure of disease prevalence, and
      levels of underreporting for the 21 most affected districts of Bihar. The average
      reproduction number (number of secondary cases generated per infective) estimates
      for Bihar range from 1.3 (2003) to 2.1 (2005) with some districts' estimates with
      mean values lower than one. Model estimates (using available data and a model
      derived expression) show that the proportion of underreported cases declined from
      an average of 88% in 2003 to 73% in 2005. However, eight districts in 2003 and
      five districts in 2005 had more than 90% levels of underreporting. Model
      estimates are used to generate underreporting adjusted incidence rates. The
      analysis finds that reported data misidentify four of the eight (2003) and three
      of the nine (2005) districts classified as high-risk. In fact, seven (2003) and
      five (2005) of the most affected Kala-azar districts had been classified as low
      risk when only reported incidence data were used.

PMID- 19769991
TI  - CSS, NIS and dynamic stability for two-species behavioral models with continuous
      trait spaces.
AB  - Static continuously stable strategy (CSS) and neighborhood invader strategy (NIS)
      conditions are developed for two-species models of frequency-dependent behavioral
      evolution when individuals have traits in continuous strategy spaces. These are
      intuitive stability conditions that predict the eventual outcome of evolution
      from a dynamic perspective. It is shown how the CSS is related to convergence
      stability for the canonical equation of adaptive dynamics and the NIS to
      convergence to a monomorphism for the replicator equation of evolutionary game
      theory. The CSS and NIS are also shown to be special cases of neighborhood p(*)-
      superiority for p(*) equal to one half and zero, respectively. The theory is
      illustrated when each species has a one-dimensional trait space.

PMID- 19769992
TI  - Universal features of surname distribution in a subsample of a growing
      population.
AB  - We examine the problem of family size statistics (the number of individuals
      carrying the same surname, or the same DNA sequence) in a given size subsample of
      an exponentially growing population. We approach the problem from two directions.
      In the first, we construct the family size distribution for the subsample from
      the stable distribution for the full population. This latter distribution is
      calculated for an arbitrary growth process in the limit of slow growth, and is
      seen to depend only on the average and variance of the number of children per
      individual, as well as the mutation rate. The distribution for the subsample is
      shifted left with respect to the original distribution, tending to eliminate the
      part of the original distribution reflecting the small families, and thus
      increasing the mean family size. From the subsample distribution, various bulk
      quantities such as the average family size and the percentage of singleton
      families are calculated. In the second approach, we study the past time
      development of these bulk quantities, deriving the statistics of the genealogical
      tree of the subsample. This approach reproduces that of the first when the
      current statistics of the subsample is considered. Surname statistics for the US
      in 1790 and 2000 and for Norway in 2008 are analyzed in the light of the theory
      and show satisfactory agreement, when the time-dependence of the growth rate is
      taken into account for the two contemporary data sets.

PMID- 19769994
TI  - An evoked auditory response fMRI study of the effects of rTMS on putative AVH
      pathways in healthy volunteers.
AB  - BACKGROUND: Auditory verbal hallucinations (AVH) are the most prevalent symptom
      in schizophrenia. They are associated with increased activation within the
      temporoparietal cortices and are refractory to pharmacological and psychological
      treatment in approximately 25% of patients. Low frequency repetitive transcranial
      magnetic stimulation (rTMS) over the temporoparietal cortex has been demonstrated
      to be effective in reducing AVH in some patients, although results have varied.
      The cortical mechanism by which rTMS exerts its effects remain unknown, although
      data from the motor system is suggestive of a local cortical inhibitory effect.
      We explored neuroimaging differences in healthy volunteers between application of
      a clinically utilized rTMS protocol and a sham rTMS equivalent when undertaking a
      prosodic auditory task. METHOD: Single-blind placebo controlled fMRI study of 24
      healthy volunteers undertaking an auditory temporoparietal activation task, who
      received either right temporoparietal rTMS or sham RTMS. RESULTS: The main effect
      of group was bilateral inferior parietal deactivation following real rTMS. An
      interaction of group and task type showed deactivation during real rTMS in the
      right superior temporal gyrus (STG), left thalamus, left postcentral gyrus and
      cerebellum. However, the left parietal lobe showed an increase in activation
      following right sided real rTMS, but this increase was specific to a non
      linguistic, tone-sequence task. CONCLUSION: rTMS does cause local inhibitory
      effects, not only in the underlying region of application, but also in
      functionally connected cortical regions. However, there is also a related, task
      dependent, increase in activation within selected cortical areas in the
      contralateral hemisphere; these are likely to reflect compensatory mechanisms,
      and such cortical activation may in some cases contribute to, or retard, some of
      the therapeutic effects seen with rTMS.

PMID- 19769995
TI  - Toxic effects of low doses of Bisphenol-A on human placental cells.
AB  - Humans are exposed daily to a great number of xenobiotics and their metabolites
      present as pollutants. Bisphenol-A (BPA) is extensively used in a broad range of
      products including baby bottles, food-storage containers, medical equipment, and
      consumer electronics. Thus, BPA is the most common monomer for polycarbonates
      intended for food contact. Levels of this industrial product are found in
      maternal blood, amniotic fluid, follicular fluid, placental tissue, umbilical
      cord blood, and maternal urine. In this study, we investigated toxic effects of
      BPA concentrations close to levels found in serum of pregnant women on human
      cytotrophoblasts (CTB). These cells were isolated from fresh placentas and
      exposed to BPA for 24 h. Our results showed that very low doses of BPA induce
      apoptosis (2 to 3 times) as assessed using M30 antibody immunofluorescent
      detection, and necrosis (1.3 to 1.7 times) as assessed through the cytosolic
      Adenylate Kinase (AK) activity after cell membrane damage. We also showed that
      BPA increased significantly the tumor-necrosis factor alpha (TNF-alpha) gene
      expression and protein excretion as measured by real-time RT-PCR and ELISA
      luminescent test, respectively. Moreover, we observed that induction of AK
      activation and TNF-alpha gene expression require lower levels of BPA than
      apoptosis or TNF-alpha protein excretion. Our findings suggest that exposure of
      placental cells to low doses of BPA may cause detrimental effects, leading in
      vivo to adverse pregnancy outcomes such as preeclampsia, intrauterine growth
      restriction, prematurity and pregnancy loss.

PMID- 19769996
TI  - Sustained active transportation is associated with a favorable body mass index
      trajectory across the early school years: findings from the Quebec Longitudinal
      Study of Child Development birth cohort.
AB  - OBJECTIVE: To determine the extent to which active transportation (AT) to and
      from school is associated with changes in body mass index (BMI) from kindergarten
      (6-year-olds) through grade 2 (8-year-olds). METHODS: The sample included 1170
      children (50.4% of baseline participants) who were part of the Quebec
      Longitudinal Study of Child Development (QLSCD), a birth cohort established in
      1998 in Quebec, Canada. Data were collected by trained interviewers using
      structured interviews and measuring height and weight in the home with the person
      most knowledgeable about the child's health. Relative weight was operationalized
      as age- and sex-adjusted BMI Z-scores. RESULTS: Growth curve analyses showed that
      using AT to and from school both when in kindergarten and in grade 1 was
      predictive of a lower BMI Z-score (coeff=-0.18, SE=0.09, p=0.05) in grade 1.
      Using AT to and from school in kindergarten, grade 1, and grade 2 was predictive
      of a lower BMI Z-score (coeff=-0.30, SE=0.098, p=0.003) in grade 2. No other
      covariates were predictive of relative weight across time, although having an
      overweight or obese mother was associated with a BMI Z-score of 0.39 (SE=0.07,
      p<0.001) across all time points. CONCLUSION: Sustained AT is associated with more
      healthful trajectories of BMI across the early school years.

PMID- 19769997
TI  - From good ideas to actions: a model-driven community collaborative to prevent
      childhood obesity.
AB  - OBJECTIVE: Activate Omaha Kids, a community collaborative, was designed,
      implemented, and evaluated with the aim of preventing childhood obesity in the
      Omaha community. Activate Omaha Kids brought together key stakeholders and
      community leaders to create a community coalition. The coalition's aim was to
      oversee a long-term sustainable approach to preventing obesity. Following a
      planning phase, a business plan was developed that prioritized best practices to
      be implemented in Omaha. METHODS: The business plan was developed using the
      Ecological Model, Health Policy Model, and Robert Wood Johnson Foundation Active
      Living by Design 5P model. The three models helped the community identify target
      populations and activities that then created a single model for sustainable
      change. RESULTS: Twenty-four initiatives were identified, over one million
      dollars in funding was secured, and evaluation strategies were identified.
      CONCLUSION: By using the models from the initial steps through evaluation, a
      clear facilitation of the process was possible, and the result was a
      comprehensive, feasible plan. The use of the models to design a strategic plan
      was pivotal in building a sustainable coalition to achieve measurable
      improvements in the health of children and prove replicable over time.

PMID- 19769998
TI  - Environmental correlates of physical activity in driving and non-driving rural
      Japanese women.
AB  - OBJECTIVE: This study examined the relationship between physical activity and the
      environment among rural Japanese women, and whether that relationship varied with
      driving status. METHODS: 434 women aged 40-64 years in Unnan City, rural Japan,
      were surveyed in 2006 about physical activity and their neighborhood
      environments. The proximity and frequency of public transport were measured using
      geographic information systems software. RESULTS: Perceived good access to public
      transport and recreational facilities, presence of bike lanes, and good
      aesthetics were among factors positively associated with being physically active.
      The interaction between the convenience of bus service and driving status was
      statistically significant (P=0.023). Non-drivers residing in areas where bus
      service was moderately convenient were more likely to be active than those who
      were without it. CONCLUSION: These findings suggested that driving status is a
      potential modifier of the relationship between physical activity and the
      convenience of bus service and that convenient bus service is important for
      promoting physical activity especially in non-drivers.

PMID- 19769993
TI  - Chronic inflammation and asthma.
AB  - Allergic asthma is a complex and chronic inflammatory disorder which is
      associated with airway hyper-responsiveness and tissue remodelling of the airway
      structure. Although originally thought to be a Th2-driven inflammatory response
      to inhaled innocuous allergen, the immune response in asthma is now considered
      highly heterogeneous. There are now various in vivo systems which have been
      designed to examine the pathways leading to the development of this chronic
      immune response and reflect, in part this heterogeneity. Furthermore, the
      emergence of endogenous immunoregulatory pathways and active pro-resolving
      mediators hold great potential for future therapeutic intervention. In this
      review, the key cellular and molecular mediators relating to chronic allergic
      airway disease are discussed, as well as emerging players in the regulation of
      chronic allergic inflammation.

PMID- 19769999
TI  - Insight into the denaturation transition of DNA.
AB  - DNA undergoes a helix-to-coil transition (also called denaturation transition)
      upon heating. This transition can also be facilitated by using solvent mixtures
      (for example water-alcohol). An increase in the hydrophobic tail of the second
      solvent molecule first decreases then increases the melting temperature
      appreciably. Measurement on 4% DNA in a series of water-alcohol mixtures shows
      that the helix-to-coil melting transition is driven by the solvent ability to
      cross the hydrophobic sugar-rich region. DNA is behaving like a cylindrical
      micelle.

PMID- 19770000
TI  - Sample purification improves the analysis of nonviral in vivo gene transfection.
AB  - Nonviral gene delivery has gained a lot of interest as a promising approach for
      gene therapy. Despite intensive studies and much progress the outcome of nonviral
      vectors has remained significantly weaker than that of viral vectors. A weak
      transfection efficiency of nonviral gene transfection is still limiting their in
      vivo use. We have tested the possibility to improve the measurement of
      transfection efficiency by increasing the sensitivity of analysis with sample
      purification. The BPVlacZ and CMVlacZ plasmids were transfected by i.v. infusion
      of the PEI/DNA complexes in the rats. An adenovirus lacZ vector was used as a
      reference. The transfection efficiency was analysed from the lungs and brain.
      Tissue samples were minced and homogenized for preparation of crude homogenates
      and for further purification of crude homogenates with a DEAE anion exchange
      chromatography. The beta-galactosidase activity was measured using a luminometric
      assay. The obtained activity of beta-galactosidase was higher in the purified
      than nonpurified samples and the analysis of transfection efficiency as beta
      galactosidase activity was improved more than 1000-fold by the purification of
      samples from perfused target tissues. An increased sensitivity of analysis by
      sample preparation may be a useful and inexpensive strategy to detect and
      estimate a low transfection efficiency or transgene expression often associated
      with a nonviral in vivo gene delivery.

PMID- 19770001
TI  - Use of the Rey-Osterrieth Complex Figure Test for neurotoxicity evaluation of
      mixtures in children.
AB  - The aim of this study was to assess the value of the children's version of the
      Rey-Osterrieth Complex Figure Test as a screening test in a population exposed to
      different mixtures of neurotoxicants. Copy and Immediate Recall scores were
      evaluated through the test. Children were recruited from three sites; an area
      with natural contamination by fluoride and arsenic (F-As), a mining-metallurgical
      area with lead and arsenic contamination (Pb-As) and a malaria zone with the
      evidence of fish contaminated with dichlorodiphenyltrichloroethane (DDT) and
      polychlorinated biphenyls (PCBs). Children aged 6-11 years old, living in one of
      the three polluted sites since birth were recruited (n=166). The exposure was
      evaluated as follows: fluoride and arsenic in urine, lead in blood and DDT,
      dichlorodiphenyldichloroethylene (DDE) and PCBs in serum. To evaluate the test
      performance, z-scores for Copy and Immediate Recall were calculated. The
      proportion of children by residence area with performance lower than expected by
      age (below -1 SD) for Copy and Immediate Recall was in the F-As area (88.7% and
      59%) and in the DDT-PCBs area (73% and 43.8%), respectively. In the Pb-As area,
      the proportion was 62% for both tests. After adjustment, Copy correlated
      inversely with fluoride in urine (r=-0.29; p<0.001) and Immediate Recall
      correlated inversely with fluoride in urine (r=-0.27; p<0.05), lead in blood (r=
      0.72; p<0.01), arsenic in urine (r=-0.63; p<0.05) and DDE (r=-0.25; p<0.05). This
      study provided evidence that children included in this research are living in
      high risk areas and were exposed to neurotoxicants. Poor performance in the test
      could be explained in some way by F, Pb, As or DDE exposure, however social
      factors or the low quality of school education prevalent in the areas could be
      playing an important role.

PMID- 19770002
TI  - Preclinical and clinical pharmacology of the GABAA receptor alpha5 subtype
      selective inverse agonist alpha5IA.
AB  - alpha5IA is a triazolophthalazine that selectively attenuates the effects of GABA
      at GABA(A) receptors containing an alpha5 subunit. It enhances long-term
      potentiation in an in vitro model of mouse hippocampal synaptic plasticity, gives
      good in vivo receptor occupancy and improves cognitive performance in normal rats
      as measured using the delayed-matching-to-place version of the Morris water maze
      yet, importantly, it is without anxiogenic or proconvulsant liabilities. The
      hydroxymethyl isoxazole metabolite, which occurs both in vitro and in vivo, has a
      very low aqueous solubility (0.6microg/mL) that resulted in renal toxicity
      (crystal formation) at very high doses in preclinical safety and toxicity
      studies. Although this precluded it from being dosed to humans over prolonged
      periods of time, alpha5IA is, nevertheless, well tolerated in young and elderly
      subjects up to a dose of 6mg in multiple-dose studies and gives a plasma EC(50)
      for alpha5IA occupancy measured using [(11)C]flumazenil PET of 10ng/mL. The
      compound was evaluated in experimental studies and although in elderly subjects
      alpha5IA does not improve performance in a paired-associate learning task (a 4-mg
      dose actually impairs performance), it is able to reverse the ethanol-induced
      impairment in performance in healthy young normal volunteers. These data
      demonstrate that in man an alpha5-selective inverse agonist may be effective at
      increasing performance under certain conditions. Whether or not such a compound
      has efficacy in conditions associated with cognitive deficits, such as attention
      deficit hyperactivity disorder, Alzheimer's disease or schizophrenia remains to
      be determined.

PMID- 19770003
TI  - Understanding the blood-brain barrier using gene and protein expression profiling
      technologies.
AB  - The blood-brain barrier (BBB) contributes to the brain homeostasis by regulating
      the passage of endogenous and exogenous compounds. This function is in part due
      to well-known proteins such as tight junction proteins, plasma membrane
      transporters and metabolic barrier proteins. Over the last decade, genomics and
      proteomics have emerged as supplementary tools for BBB research. The development
      of genomic and proteomic technologies has provided several means to extend the
      BBB knowledge and to investigate additional routes for the bypass of this
      barrier. These profiling technologies have been used on BBB models to decipher
      the physiological characteristics and, under stress conditions, to understand the
      molecular mechanisms of brain diseases. In this review, we will report and
      discuss the genomic and proteomic studies recently carried out to enhance the
      understanding of BBB features.

PMID- 19770004
TI  - Rational design of a classical swine fever C-strain vaccine virus that enables
      the differentiation between infected and vaccinated animals.
AB  - The C-strain of the classical swine fever virus (CSFV) is considered the gold
      standard vaccine for the control of CSF. This vaccine, however, does not enable
      the serological differentiation between infected and vaccinated animals (DIVA).
      Consequently, its use can impose severe trade restrictions. The immunodominant
      and evolutionarily conserved A-domain of the E2 structural glycoprotein is an
      important target in CSFV-specific ELISAs. With the ultimate aim to render the C
      strain suitable as a DIVA vaccine, mutations were introduced that were expected
      to dampen the immunogenicity of the A-domain. In the first of two approaches, the
      feasibility of shielding the A-domain by N-linked glycans was evaluated, whereas
      in the second approach C-strain mutants were created with targeted deletions in
      the A-domain. Analysis of the antibody responses elicited in rabbits suggested
      that shielding of the A-domain by an N-linked glycan had a minor effect on the
      immune response against the A-domain, whereas a targeted deletion of only a
      single amino acid severely dampened this response. C-strain mutants with larger
      deletions were highly debilitated and incapable of sustained growth in vitro. By
      providing the viruses with the opportunity to increase their fitness by mutation,
      a mutant was rescued that found a way to compensate for the imposed fitness cost.
      Most of the identified mutations occurred in several independently evolved
      viruses, demonstrating parallel evolution. By virtue of this compensatory
      evolution, a well replicating and genetically stable C-strain mutant was produced
      that can be serologically differentiated from wildtype CSFV. The findings provide
      the molecular basis for the development of a novel, genetically stable, live
      attenuated CSF DIVA vaccine.

PMID- 19770005
TI  - Resistin is stored in neutrophil granules being released upon challenge with
      inflammatory stimuli.
AB  - We have recently shown that resistin is a key mediator of arthritis accumulating
      in the inflamed joints and exerting its pro-inflammatory properties independently
      of TNFalpha. Here we evaluate neutrophils as a cellular source of resistin. Human
      neutrophils were subjected to subcellular fractionation where the presence of
      resistin was assessed using western blot, ELISA, and mass spectrometry. Presence
      of resistin on the neutrophil surface was visualized by flow cytometry. More than
      95% of the neutrophils in circulation and in synovial fluid express resistin on
      their surface. Stimulation of mature neutrophils with fMLF induced release of
      resistin into supernatants and increased expression of resistin on the surface.
      Resistin is mobilized simultaneously with lactoferrin, a protein found in
      specific granules, and with granule-stored CR3/CD11b. Subcellular fractionation
      of human neutrophils demonstrated the presence of resistin in azurophilic and in
      specific granules. Here we show that neutrophils have two pools of resistin, the
      major one exists in specific granules, and the second on their cell membrane.
      Release of resistin from the neutrophil granules probably serves the main source
      of resistin at the site of inflammation.

PMID- 19770006
TI  - Effects of explicit and implicit perseverative cognition on cardiac recovery
      after cognitive stress.
AB  - Slow cardiovascular (CV) recovery after stress is a predictor of adverse CV
      outcomes. Perseverative cognition (PC) about stress has been hypothesized to co
      determine slow recovery. In the present study, it was investigated whether two
      types of trait PC, i.e. trait worry and trait rumination, predicted delayed
      cardiac recovery after a cognitive stressor. Furthermore, it was examined whether
      explicit state PC (i.e. negative intrusive thoughts) or implicit state PC (i.e.
      automatic vigilance) additionally predicted delayed cardiac recovery. Fifty-nine
      participants performed a stressful task, which consisted of an unsolvable synonym
      task. After a 6-minute recovery period, participants reported on their level of
      negative intrusive thoughts (i.e. explicit state PC), and performed a lexical
      decision task (LDT) to measure automatic vigilance for task-related information
      (i.e. implicit state PC). Cardiac activity was continuously measured using heart
      rate (HR) and heart rate variability (HRV). Trait worry and rumination were
      measured by the Penn State Worry Questionnaire (PSWQ) and the Ruminative Response
      Scale (RRS), respectively. The results showed that high trait worriers had a
      slower HR recovery from the cognitive stressor compared to low trait worriers.
      They also showed delayed HRV recovery, but only when the tendency to dwell upon
      one's negative mood (the 'brooding' subscale of the RRS) was low. Slow HR
      recovery was associated with high levels of negative intrusive thoughts and with
      automatic vigilance, but in the unexpected direction for the latter. These
      results provide evidence that delayed cardiac recovery is associated with trait
      as well as state PC, and suggest that brooding attenuates the HRV suppressing
      effect of high trait worry.

PMID- 19770007
TI  - Restoring 3'-5' exonuclease activity of thermophilic Geobacillus DNA polymerase I
      using site-directed mutagenesis in active site.
AB  - Three-dimensional structure and alignment analyses of 3'-5' exonuclease domain of
      DNA polymerase I from thermophilic Geobacillus sp. MKK show that the key
      catalytic amino acids in 3'-5' exonuclease domain are changed and the enzyme
      looses the activity. In order to render the activity, a catalytic module is
      constructed in the active site using site-directed mutagenesis. Seven mutant
      clones of the enzyme are generated containing: M1 (V319D, E325L), M2 (A376D), M3
      (D425F), M4 (InsY446, K450D), M12 (V319D, E325L, A376D), M123 (V319D, E325L,
      A376D, D425F), and M1234 (V319D, E325L, A376D, D425F, InsY446, K450D). In
      addition, a chimera MkkEc polymerase is constructed by exchanging 3'-5'
      exonuclease domain of the MKK polymerase (residues 301-466) with the same domain
      of homologous Escherichia coli polymerase (residues 327-519). For the first time,
      all essential amino acids for the 3'-5' exonuclease activity are introduced in
      one mutant. As a result, among all mutants, only M1234 and MkkEc mutants show
      significant 3'-5' exonuclease activity. Moreover, M1234 mutant was kept most of
      its polymerase activity while the activity of MkkEc mutants is decreased
      dramatically compared to the wild type enzyme.

PMID- 19770008
TI  - Heterologous expression of the methyl carbamate-degrading hydrolase MCD.
AB  - The methyl carbamate-degrading hydrolase (MCD) of Achromobacter WM111 has
      considerable potential as a pesticide bioremediation agent. However this
      potential has been unrealisable until now because of an inability to express MCD
      in heterologous hosts such as Escherichia coli. Herein, we describe the first
      successful attempt to express appreciable quantities of MCD in active form in E.
      coli, and the subsequent characterisation of the heterologously expressed
      material. We find that the properties of this material closely match the
      previously reported properties of MCD produced from Achromobacter WM111. This
      includes the presence of two distinct forms of the enzyme that we show are most
      likely due to the presence of two functional translational start sites. The
      purified enzyme catalyses the hydrolysis of a carbamate (carbaryl), a carboxyl
      ester (alpha-naphthyl acetate) and a phophotriester (dimethyl umbelliferyl
      phosphate) and it is relatively resistant to thermal and solvent-mediated
      denaturation. The robust nature and catalytic promiscuity of MCD suggest that it
      could be exploited for various biotechnological applications.

PMID- 19770009
TI  - Transcriptome and proteome analysis of Chinese hamster ovary cells under low
      temperature and butyrate treatment.
AB  - Recombinant Chinese hamster ovary (CHO) cells selected for high productivity are
      capable of secreting immunoglobulin G (IgG) molecules at a level that rivals
      plasma cells in vivo. Following butyrate treatment at 33 degrees C, further
      increases in productivity are observed. To better understand the mechanisms by
      which this increased productivity is incurred, the transcriptional response of an
      antibody-producing cell line undergoing these treatments was investigated using
      oligo-DNA microarrays. Using distance calculations, more than 900 genes were
      identified as kinetically differentially expressed between the butyrate-treated
      33 degrees C culture and the untreated culture. Furthermore, transcript levels of
      the heavy and light chain IgG genes increased following treatment. Using stable
      isotope labeling (SILAC), the secretion rate of IgG was investigated by tracking
      the decay of the isotope label upon switching to unlabeled medium. Both treated
      and untreated cultures exhibited very similar IgG secretion kinetics. In
      contrast, the intracellular IgG content was found to be elevated following
      treatment. This result suggests that increased productivity under treatment is
      attributable to elevated cellular secretory capacity, rather than shorter holding
      times in the secretory pathway. This hypothesis is further supported by the
      results of gene set enrichment analysis (GSEA), which revealed that elements of
      the secretory pathway, including Golgi apparatus, cytoskeleton protein binding
      and small GTPase-mediated signal transduction are enriched and thus may play a
      role in the increased recombinant protein production observed under butyrate
      treatment at 33 degrees C.

PMID- 19770010
TI  - Preparation and characterization of folate-poly(ethylene glycol)-grafted
      trimethylchitosan for intracellular transport of protein through folate receptor
      mediated endocytosis.
AB  - To develop a receptor-mediated intracellular delivery system that can transport
      therapeutic proteins to specific tumor cells, folate-poly(ethylene glycol)
      grafted-trimethylchitosan (folate-PEG-g-TMC) was synthesized. Nano-scaled
      spherical polyelectrolyte complexes between the folate-PEG-g-TMC and fluorescein
      isothiocyanate conjugated bovine serum albumin (FITC-BSA) were prepared under
      suitable weight ratio of copolymer to FITC-BSA by ionic interaction between the
      positively charged copolymers and the negatively charged FITC-BSA. Intracellular
      uptake of FITC-BSA was specifically enhanced in SKOV3 cells (folate receptor over
      expressing cell line) through folate receptor-mediated endocytosis compared with
      A549 cells (folate receptor deficient cell line). Folate-PEG-g-TMC shows promise
      for intracellular transport of negatively charged therapeutic proteins into
      folate receptor over-expressing tumor cells.

PMID- 19770011
TI  - Hydrogel-based protein and oligonucleotide microchips on metal-coated surfaces:
      enhancement of fluorescence and optimization of immunoassay.
AB  - Manufacturing of hydrogel-based microchips on metal-coated substrates
      significantly enhances fluorescent signals upon binding of labeled target
      molecules. This observation holds true for both oligonucleotide and protein
      microchips. When Cy5 is used as fluorophore, this enhancement is 8-10-fold in
      hemispherical gel elements and 4-5-fold in flattened gel pads, as compared with
      similar microchips manufactured on uncoated glass slides. The effect also depends
      on the hydrophobicity of metal-coated substrate and on the presence of a layer of
      liquid over the gel pads. The extent of enhancement is insensitive to the nature
      of formed complexes and immobilized probes and remains linear within a wide range
      of fluorescence intensities. Manufacturing of gel-based protein microarrays on
      metal-coated substrates improves their sensitivity using the same incubation time
      for immunoassay. Sandwich immunoassay using these microchips allows shortening
      the incubation time without loss of sensitivity. Unlike microchips with probes
      immobilized directly on a surface, for which the plasmon mechanism is considered
      responsible for metal-enhanced fluorescence, the enhancement effect observed
      using hydrogel-based microchips on metal-coated substrates might be explained
      within the framework of geometric optics.

PMID- 19770012
TI  - Engineering of a parainfluenza virus type 5 fusion protein (PIV-5 F): development
      of an autonomous and hyperfusogenic protein by a combinational mutagenesis
      approach.
AB  - The entry of enveloped viruses into host cells is accomplished by fusion of the
      viral envelope with the target cell membrane. For the paramyxovirus parainfluenza
      virus type 5 (PIV-5), this fusion involves an attachment protein (HN) and a class
      I viral fusion protein (F). We investigated the effect of 20 different
      combinations of 12 amino-acid substitutions within functional domains of the PIV
      5 F glycoprotein, by performing cell surface expression measurements,
      quantitative fusion and syncytia assays. We found that combinations of mutations
      conferring an autonomous phenotype with mutations leading to an increased fusion
      activity were compatible and generated functional PIV-5 F proteins. The addition
      of mutations in the heptad-repeat domains led to both autonomous and
      hyperfusogenic phenotypes, despite the low cell surface expression of the
      corresponding mutants. Such engineering approach may prove useful not only for
      deciphering the fundamental mechanism behind viral-mediated membrane fusion but
      also in the development of potential therapeutic applications.

PMID- 19770013
TI  - A novel human protein is able to interact with hepatitis B virus core deletion
      mutant but not with the wild-type protein.
AB  - Hepatitis B virus mutants with in-frame deletions in the central part of the core
      gene are associated with a severe course of infection in long-term
      immunosuppressed renal transplant recipients. In this study, yeast two-hybrid
      system was employed to investigate interaction capabilities of two core mutants
      with deleted 77-93 and 86-93 amino acids. The same mutant and wild-type (WT)
      protein pairs which form core-like particles inside bacterial cells were able to
      interact also in two-hybrid system. To find host proteins possibly involved in
      enhanced pathogenesis of the mutant variants, a human hepatocyte cDNA library was
      screened for proteins interacting with the mutant but not with the WT core
      protein. A human protein of unknown function FLJ20850 interacted specifically
      with the mutant proteins. An attempt to determine interacting regions revealed
      that FLJ20850 was unable to interact without significant parts of its C- or N
      end, and introduced deletion in the central region conferred interaction
      capability to the WT core protein.

PMID- 19770014
TI  - Design of novel histone-derived antimicrobial peptides.
AB  - Previous studies have identified several naturally occurring antimicrobial
      peptides derived from histone proteins. This research aimed to design novel
      histone-derived antimicrobial peptides (HDAPs). To this end, three novel peptides
      (DesHDAP1, DesHDAP2, and DesHDAP3) were designed based on a histone-DNA crystal
      structure and structural properties of buforin II, the best characterized
      naturally occurring HDAP. Molecular dynamics simulations and circular dichroism
      spectroscopy were used to further support the predicted structure and potential
      nucleic acid interactions of these three designed peptides. The antibacterial
      activity of the three peptides was then verified experimentally against a series
      of bacterial strains using a radial diffusion assay. One of these peptides is the
      first known fragment of histone H3 with antibacterial properties. Optical density
      measurements of bacterial cells exposed to the designed peptides implied that at
      least two of the novel peptides can induce cell death without causing significant
      membrane permeabilization, as observed for buforin II. The antibacterial potency
      of these designed HDAPs does not appear to correlate with their overall alpha
      helical content, unlike previous observations for analogs of buforin II. However,
      the most potent designed peptide, DesHDAP1, shares a markedly similar circular
      dichroism spectrum with buforin II. These results demonstrate the potential of
      using histone structures as a framework for designing novel antimicrobial
      peptides. As well, these studies represent an important starting point for a
      broader characterization of properties shared by HDAPs.

PMID- 19770015
TI  - Differential elicitation of an aspartic protease inhibitor: regulation of
      endogenous protease and initial events in germination in seeds of Vigna radiata.
AB  - Plant aspartic proteases are of recent origin with their physiological
      significance in crucial processes emerging. Reports on the significance of
      aspartic protease inhibitors and their endogenous proteases in seeds of plants
      are scanty. This paper reports the purification of an aspartic protease inhibitor
      from the seeds of Vigna radiata, its control of the endogenous aspartic protease
      and their subsequent role in the early germination events. The role of the
      aspartic protease inhibitor and the enzyme in initial stages of germination of V.
      radiata has been tracked by differential timed expression and germination assays.
      The expression pattern revealed maximum expression of the inhibitor in the
      dormant seeds while the enzyme was predominant in the germinating seeds. Their
      expression patterns and interactions indicate their significance in initiation of
      germination. The expression of other classes of proteases was monitored during
      germination and a model predicting the events occurring during proteolysis of the
      storage protein in germination is hypothesized. The inhibitor was a linear,
      hydrophobic, pH stable and thermostable peptide with molecular weight of 1660 Da.
      The purified inhibitor showed a pI of 4.36 with the sequence as AEIYN KDGNK
      LDLYG. The inhibitor was found to be stable in a broad range of pH from 2 to 10
      with an optimum of 3.0. The half-life of VrAPI at 100 degrees C was 30 min
      whereas the maximum activity was observed at 37 degrees C. The initial kinetic
      analysis of the inhibitor against the endogenous protease showed an IC(50) value
      of 11 nM while the value of the inhibition rate constant K(i) was 34 x 10(-9)M.

PMID- 19770016
TI  - DHA enhances the noradrenaline release by SH-SY5Y cells.
AB  - Polyunsaturated fatty acids (PUFAs), particularly docosahexaenoic acid (DHA) and
      arachidonic acid (AA), are the main components of the phospholipids, in cerebral
      membranes. A dietary-induced cerebral DHA deficit results in altered behaviour
      and neurotransmission in rodents. To determine whether PUFA were acting on the
      neurotransmitter release machinery, we measured the release of [(3)H]
      noradrenaline (NA) from SH-SY5Y neuroblastoma cells with modified PUFA membrane
      contents and from cells incubated with medium containing high DHA or AA. The
      membranes of cells incubated with 70 microM DHA for 3 days had 7.6-times more DHA
      in their ethanolamine glycerophospholipids, while the membranes of cells
      incubated with AA had 40% less. Incorporation of DHA enhanced basal [(3)H]-NA
      release (25%, p<0.05), but not KCl-evoked [(3)H]-NA release. Brief incubation
      with DHA during vesicle mobilization also strongly increased [3H]-NA release. AA
      had no effect. The genes encoding for the calcium sensor synaptotagmin 1, and for
      the two SNARE complex proteins syntaxin 1A and synaptobrevin 1 were not affected
      by PUFA incorporation, as indicated by assays for specific mRNAs and proteins.
      Thus both a high membrane DHA content and free DHA in the medium enhance the
      release of [(3)H]-NA from SH-SY5Y cells. This suggests that brain membrane DHA
      influences exocytosis, which then regulates neurotransmission.

PMID- 19770017
TI  - A framework for using structural, reactivity, metabolic and physicochemical
      similarity to evaluate the suitability of analogs for SAR-based toxicological
      assessments.
AB  - A systematic expert-driven process is presented for evaluating analogs for read
      across in SAR (structure activity relationship) toxicological assessments. The
      approach involves categorizing potential analogs based upon their degree of
      structural, reactivity, metabolic and physicochemical similarity to the chemical
      with missing toxicological data (target chemical). It extends beyond structural
      similarity, and includes differentiation based upon chemical reactivity and
      addresses the potential that an analog and target could show toxicologically
      significant metabolic convergence or divergence. In addition, it identifies
      differences in physicochemical properties, which could affect bioavailability and
      consequently biological responses observed in vitro or in vivo. The approach
      provides a stepwise decision tree for categorizing the suitability of analogs,
      which qualitatively characterizes the strength of the evidence supporting the
      hypothesis of similarity and level of uncertainty associated with their use for
      read across. The result is a comprehensive framework to apply chemical,
      biochemical and toxicological principles in a systematic manner to identify and
      evaluate factors that can introduce uncertainty into SAR assessments, while
      maximizing the appropriate use of all available data.

PMID- 19770018
TI  - Targeting excessive free radicals with peels and juices of citrus fruits:
      grapefruit, lemon, lime and orange.
AB  - A comparative study between the antioxidant properties of peel (flavedo and
      albedo) and juice of some commercially grown citrus fruit (Rutaceae), grapefruit
      (Citrus paradisi), lemon (Citrus limon), lime (Citrusxaurantiifolia) and sweet
      orange (Citrus sinensis) was performed. Different in vitro assays were applied to
      the volatile and polar fractions of peels and to crude and polar fraction of
      juices: 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging capacity,
      reducing power and inhibition of lipid peroxidation using beta-carotene-linoleate
      model system in liposomes and thiobarbituric acid reactive substances (TBARS)
      assay in brain homogenates. Reducing sugars and phenolics were the main
      antioxidant compounds found in all the extracts. Peels polar fractions revealed
      the highest contents in phenolics, flavonoids, ascorbic acid, carotenoids and
      reducing sugars, which certainly contribute to the highest antioxidant potential
      found in these fractions. Peels volatile fractions were clearly separated using
      discriminant analysis, which is in agreement with their lowest antioxidant
      potential.

PMID- 19770019
TI  - Limettin and furocoumarins in beverages containing citrus juices or extracts.
AB  - Phototoxic and photo-genotoxic furocoumarins occur, e.g., in citrus species,
      parsnip, parsley, celery, and figs. They exhibit phototoxic and photo-genotoxic
      properties in combination with UV radiation, while less is known about the
      phototoxicity of the coumarin derivative limettin mainly found in limes and
      lemons. Risk assessment of dietary furocoumarins is based on a threshold approach
      and on estimates of 1.2-1.45 mg for the average daily exposure for adults via the
      diet in several countries. In these estimates, the major contribution to overall
      daily exposure has been attributed to citrus-flavored non-alcoholic beverages, in
      spite of a lack of analytical data for those products. Therefore, we analyzed a
      number of furocoumarins in a variety of citrus-containing beverages and included
      limettin in the pattern of analyzed constituents. Our findings provide strong
      evidence that grapefruit juice and not citrus-flavored non-alcoholic beverages is
      the major source of furocoumarin exposure in a Western diet. Based on these
      findings it can be assumed that the average dietary exposure to furocoumarins is
      about 3-fold lower than previously estimated, i.e. in the range of 548 and 2237
      microg/day for the average and high consumer, respectively. The coumarin
      derivative limettin was mainly found in lime products.

PMID- 19770020
TI  - Genotoxicity assessment of chromium(III) propionate complex in the rat model
      using the comet assay.
AB  - The aim of the study was to assess genotoxicity of a chromium(III) propionate
      complex in rat's peripheral blood lymphocytes by the comet assay. The study was
      carried out on 18 12-weeks old female Wistar rats that were divided into three
      equal groups (six animals each): control (0), control-Cr(VI) and Cr(III)-tested
      rat fed ad libitum a basal diet and the diet supplemented either with 10 mg
      Cr(VI)/kg diet (given as K(2)Cr(2)O(7), equivalent of 1mg/kg body mass/day) or
      1000 mg Cr(III)/kg diet (given as [Cr(3)O(O(2)CCH(2)CH(3))6(H(2)O)(3)]NO(3)),
      equivalent of 100mg Cr/kg body mass/day) for 4 weeks. High doses of supplementary
      Cr(III) were found to not affect body mass gain, feeding efficiency ratio and
      internal organ masses. Treatment of rats with the Cr(III) propionate complex, in
      contrast to Cr(VI), did not affect significantly the comet assay results in
      lymphocytes, which suggests that the compound does not exert genotoxic effects in
      rats.

PMID- 19770021
TI  - Evaluation of the protective role of melatonin on the behavioral effects of
      aluminum in a mouse model of Alzheimer's disease.
AB  - In this study, five months old female transgenic (Tg2576) and wild-type mice were
      exposed for 6 months to aluminum (1mg Al/g diet), melatonin (10mg/kg/day), Al
      plus melatonin, or vehicle only (control group). General motor activity was
      evaluated using an open-field, whereas spatial learning and memory were assessed
      in a water maze. Aluminum levels in hippocampus, cortex and cerebellum were
      determined. Aluminum-treated Tg2576 mice showed higher Al levels in hippocampus
      than non-Al treated animals. No Al effects on general motor activity were found,
      while the open-field test showed an increased number of rearings in Tg2576 mice.
      A lower habituation pattern was observed in melatonin-treated animals.
      Differences in learning were noted in the water maze acquisition test, in which
      Al-treated Tg2576 mice showed more difficulties in learning the task than Al
      exposed wild mice. No significant effects of melatonin in the acquisition task
      were observed. The present results indicate that Tg2576 mice are sensitive to
      high dietary Al levels. A significant protector role of melatonin on Al-induced
      behavioral effects was not observed.

PMID- 19770022
TI  - Synaptic plasticity in the subiculum.
AB  - The subiculum is the principal target of CA1 pyramidal cells. It functions as a
      mediator of hippocampal-cortical interaction and has been proposed to play an
      important role in the encoding and retrieval of long-term memory. The cellular
      mechanisms of memory formation are thought to include long-term potentiation
      (LTP) and depression (LTD) of synaptic strength. This review summarizes the
      contemporary knowledge of LTP and LTD at CA1-subiculum synapses. The observation
      that the underlying mechanisms of LTP and LTD at CA1-subiculum synapses correlate
      with the discharge properties of subicular pyramidal cell reveals a novel and
      intriguing mechanism of cell-specific consolidation of hippocampal output.

PMID- 19770023
TI  - Sex Hormone-Binding Globulin (SHBG), estradiol and breast cancer.
AB  - The human serum Sex Hormone-Binding Globulin (SHBG) plays an important role in
      breast cancer pathophysiology and risk definition, since it regulates the
      bioavailable fraction of circulating estradiol. We here summarize data reported
      over the years concerning the involvement of SHBG and SHBG polymorphisms in the
      definition of breast cancer risk. We also report what is known about the direct
      action of SHBG in breast cancer cells, illustrating its interaction with these
      cells and the subsequent initiation of a specific intracellular pathway leading
      to cross-talk with the estradiol-activated pathway and, finally, to the
      inhibition of several effects of estradiol in breast cancer cells. In conclusion,
      as a result of its unique property of regulating the estrogen free fraction and
      cross-talking with the estradiol pathways, by inhibiting estradiol-induced breast
      cancer cell growth and proliferation, SHBG is associated with a reduced risk of
      developing the neoplasm after estrogen exposure.

PMID- 19770024
TI  - Motor imagery influences the execution of repetitive finger opposition movements.
AB  - Motor imagery (MI) is the ability to imagine performing a movement without
      executing it. In literature, there have been numerous reports on the influence of
      MI on motor practice and the beneficial effects of "mental practice" on the
      physical performance has been suggested to rely to the close temporal association
      between motor rehearsal and actual performance. In the present study, we aimed to
      evaluate whether the addition of a period of motor imagery between two motor
      practice trials could modify movement execution in a repetitive finger opposition
      motor task performed at maximal speed and whether the effect of motor imagery on
      motor practice is dependant on the complexity of movement. We observed that the
      addition of motor imagery to the sole motor practice was able to influence the
      performance of repetitive finger opposition movements inducing an increase of the
      velocity of movement greater than that observed with the motor practice alone.
      Further the addition of motor imagery was able to induce a modification in the
      motor strategy in terms of duration of the main phases of movements. This was
      more evident when subjects executed a finger sequential task with respect to a
      simple finger tapping task. We assume that mental rehearsal facilitates the brain
      network involved in sensorimotor control, particularly acting on those neural
      structures involved in the motor program.

PMID- 19770025
TI  - Genomic organization and embryonic expression of miR-430 in medaka (Oryzias
      latipes): insights into the post-transcriptional gene regulation in early
      development.
AB  - MicroRNAs (miRNAs, miRs) are short noncoding RNA molecules that negatively
      control the target mRNAs by binding to the 3' untranslated region (UTR). Previous
      studies have demonstrated that miR-430 is encoded by a clustered multigene family
      and is abundantly expressed in early development. In zebrafish, miR-430 is needed
      to suppress primordial germ cell (PGC)-specific genes, such as nanos1, in somatic
      cells. However, the molecular characteristics of the miR-430 family in other
      teleost species have not been reported, and it is unclear whether such a function
      of miR-430 in PGC specification is a conserved feature of animals or not. In
      medaka (Oryzias latipes), a distantly related teleost, it has been suggested that
      PGC might be established in a different mode of specification from that of
      zebrafish. We characterized 16 miR-430 precursors in the medaka genomic sequence.
      These miR-430 genes form clusters on chromosome 4, which might share its
      evolutionary origin with that of the very large miR-430 clusters in zebrafish
      chromosome 4. However, none of the medaka miR-430 genes are identical to the
      zebrafish miR-430 paralogs. Medaka miR-430 expression starts during epiboly and
      decreases after axis formation. Functional analysis using reporter gene
      constructs showed that miR-430 repressed protein expression by binding to the
      3'UTR of zebrafish TDRD7. Consistently, the 3'UTR of medaka TDRD7 contains at
      least two significant candidates for the putative miR-430 binding site. The
      ubiquitous and early expression of medaka miR-430 and its ability to downregulate
      GFP:TDRD7 reporter mRNA imply that miR-430 has a conserved role in early
      embryogenesis. Smaller copy numbers of miR-430 genes and relatively brief
      expression in medaka might represent the characteristics of this miRNA family in
      the common ancestor of teleosts. Changes in the relationships between miR-430 and
      the target mRNA might be related to differences in the localization patterns of
      PGC-related genes in medaka and zebrafish.

PMID- 19770026
TI  - Assessment of the dermal and ocular irritation potential of multi-walled carbon
      nanotubes by using in vitro and in vivo methods.
AB  - In view of increase in the manufacture of various nanomaterials runs the risk of
      increased human exposure, in vitro screening will serve as a preliminary method
      to assess possible risk in animal studies. We attempted to know whether the
      validated in vitro alternative models established for chemicals, drugs,
      pesticides are suitable for nanomaterials, since these materials differ largely
      and may interfere with commonly used test systems. In vitro and in vivo studies
      on ocular and dermal irritation were carried out with two different sizes of
      multi-walled carbon nanotubes (MWCNT). The results of acute eye irritation
      toxicity studies with two different sizes of MWCNT in rabbits demonstrated
      reversible conjunctival redness and discharge and exhibited minimal concern while
      acute dermal irritation studies indicated that MWCNT of two sizes were non
      irritant to the skin of rabbits. Both the sizes of MWCNT revealed non-irritant
      result in HE-CAM test. In vitro skin (EPISKIN) irritation studies revealed that
      two sizes of MWCNT are non-irritant to skin. In conclusion this work purports,
      the future of alternative research lies in the validation of the methodology for
      nanomaterials.

PMID- 19770027
TI  - "Intelligent" nanoassembly for gene delivery: in vitro transfection and the
      possible mechanism.
AB  - A new "intelligent" nanoassembly (INA), consisting of a condensed core of pDNA
      with protamine sulfate (PS) and a dioleoylphosphatidyl ethanolamine (DOPE)-based
      lipid envelope containing poly(ethylene glycol)-disulfide-DOPE (PSD), was
      designed and investigated. The in vitro release experiment was carried out in
      solution containing 10mM of Glutathione, which reflected the redox potential of
      the intracellular environment. The experimental result indicated that PSD
      possessed a good ability of self-dePEGylation and could result in efficient
      release of content in the reductive environment. INAs showed higher transfection
      efficiency and much lower cytotoxicity compared with Lipofectamine 2000 on HEK
      293 cells. Cellular uptake and subcellular localization, as well as the
      quantitation of nuclear transfer demonstrated that the superior transfection
      efficiency of INAs could result from both enhanced cellular uptake mediated by
      DOPE and efficient nuclear delivery mediated by PS. The biodistribution of INAs
      in nude mice bearing tumor implied that this PSD-based nanoassembly loading
      PS/DNA could be a promising gene delivery system for tumor therapy.

PMID- 19770028
TI  - Transfection efficiencies of PAMAM dendrimers correlate inversely with their
      hydrophobicity.
AB  - Dendriplexes were characterized by ethidium bromide intercalation assay and their
      transfection efficiency was studied using HEK 293 cells and human mesenchymal
      stem cells. PAMAM G4 showed a higher transfection efficiency than PAMAM G3-G6, G4
      OH, G4-25% or G4-50% dendrimers. Substitution of OH groups for the NH(2) surface
      groups rendered the dendrimer unable to form dendriplexes and to transfect cells.
      Partial (25%) substitution of CH(3) groups for the NH(2) groups markedly impaired
      transfection; 50% substitution decreased the ability of PAMAM G4 to transfect
      threefold. It was concluded that increased hydrophobicity decreased the ability
      of dendrimers to transfect. PAMAM G4-50% is highly hydrophobic and forms micelles
      in solution, which can transfect pGFP. The results of ethidium bromide
      intercalation assays, ANS fluorescence studies and transfection efficiencies of
      PAMAM dendrimers were correlated. Subsequently, we constructed a neurotrophin
      encoding plasmid and studied its delivery to mesenchymal stem cells using PAMAM
      G4 dendrimer and Lipofectamine 2000. Lipofectamine 2000 was a more effective
      carrier (18.5%) than PAMAM G4 dendrimer (1.2%).

PMID- 19770029
TI  - Pharmacokinetics, tissue distribution and safety of cinnarizine delivered in
      lipid emulsion.
AB  - The aim of this study was to assess the potential of cinnarizine loaded in lipid
      emulsion to modify the pharmacokinetics, tissue distribution and safety of
      cinnarizine. The cinnarizine-loaded emulsion (CLE) which can remain stable over
      18-month storage at 4+/-2 degrees C was prepared by high-pressure homogenization.
      Nicomp 380 particle sizing system and HPLC were used to evaluate CLE in vitro,
      while UPLC/MS/MS for pharmacokinetic and tissue distribution study. The
      pharmacokinetics and tissue distributions of CLE were assessed by comparing with
      the solution form after intravenous administration to rats at a dose of 2mg/kg.
      The CLE showed significant higher AUC and lower clearance and distribution volume
      than those of solution form. This helped cinnarizine to reach higher level in
      vessel, and circulate in the blood stream for a longer time resulting in better
      therapeutic effect. The tissue distribution exhibited significant lower uptake of
      CLE emulsion in lung and brain, indicating the advantage of CLE over the solution
      form in reducing drug precipitation in vivo and toxicity in CNS. Drug safety
      assessment studies including hemolysis test, intravenous stimulation and
      injection anaphylaxis revealed that the CLE was safe for intravenous injection.

PMID- 19770030
TI  - Chrysanthemum morifolium Ramat (CM) extract protects human neuroblastoma SH-SY5Y
      cells against MPP+-induced cytotoxicity.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Chrysanthemum morifolium Ramat (Asteraceae) has
      (CM) long been used in Korean and Chinese traditional herbal medicines with
      numerous therapeutic applications. AIM OF THE STUDY: To evaluate the
      neuroprotective activities of Chrysanthemum morifolium (CM) extract against 1
      methyl-4-phenylpridinium ions (MPP(+)), Parkinsonian toxin through oxidative
      stress and impaired energy metabolism, in human SH-SY5Y neuroblastoma cells and
      the underlying mechanisms. MATERIALS AND METHODS: The effects of CM against
      MPP(+)-induced cytotoxicity and neuronal cell viability, oxidative damage, the
      expression of Bcl-2 and Bax, caspase-3 and poly(ADP-ribose) polymerase (PARP)
      proteolysis were evaluated by using SH-SY5Y neuroblastoma cells. RESULTS: CM
      effectively inhibited the cytotoxicity and improved cell viability. CM also
      attenuated the elevation of reactive oxygen species (ROS) level, increase in
      Bax/Bcl-2 ratio, cleavage of caspase-3 and PARP proteolysis. CONCLUSION: These
      results demonstrate that CM possesses potent neuroprotective activity and
      therefore, might be a potential candidate in neurodegenerative diseases such as
      Parkinson's disease.

PMID- 19770031
TI  - Suppression of lipopolysaccharide-induced inflammatory responses in RAW 264.7
      murine macrophages by aqueous extract of Clinopodium vulgare L. (Lamiaceae).
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The wild basil Clinopodium vulgare L. is commonly
      used in Bulgarian folk medicine for treatment of irritated skin, mastitis- and
      prostatitis-related swelling, as well as for some disorders accompanied with
      significant degree of inflammation (e.g. gastric ulcers, diabetes, and cancer).
      AIM OF STUDY: To determine the effect of aqueous extract of Clinopodium vulgare
      L. on LPS-induced inflammatory responses of murine RAW 264.7 macrophages.
      MATERIALS AND METHODS: Cell cytotoxicity was evaluated by MTT assay. Protein
      expression levels were monitored by Western blot analysis. Production of NO and
      PGE(2) was measured by the Griess colorimetric method and enzyme immunoassay,
      respectively. Activation of MMP-9 was visualized by gelatin zymography. Cytokine
      levels were determined by BioPlex assay. Intracellular ROS and free radical
      scavenging potential were measured by DCFH-DA and DPPH method, respectively.
      Xanthine oxidase activity was evaluated spectrophotometrically. RESULTS: The
      extract suppresses NF-kappaB activation by preventing I kappa-B phosphorylation
      and inhibits the phosphorylation of p38 and SAPK/JNK MAPKs. It down-regulates
      iNOS expression which manifests as a drastic decrease of NO production, inhibits
      MMP-9 activation, but does not affect COX-2 protein levels and reduces only
      slightly the released PGE(2). Secretion of IL-1 beta and Il-10 is greatly
      reduced, whereas suppression of TNF-alpha and GM-CSF production is less dramatic.
      The extract has strong free radical scavenging properties and exerts inhibitory
      effect on xanthine oxidase activity, which lowers the levels of intracellular
      ROS. CONCLUSION: The study provides evidence for the anti-inflammatory potential
      of Clinopodium vulgare L. aqueous extract.

PMID- 19770032
TI  - Black tea theaflavins extend the lifespan of fruit flies.
AB  - Black tea extract (BTE) is a mixture of epicatechins and theaflavins. The present
      study investigated the effect of BTE on the lifespan of Drosophila melanogaster.
      Results showed the mean lifespan was significantly extended from 51 to 56days
      upon BTE treatment. Gene expression of superoxide dismutase (SOD1 and SOD2),
      catalase (CAT), and methuselah (MTH) was characterized by an increase in young
      and then a decrease in aged fruit flies. Higher gene expression of SOD1 and CAT
      was observed in the BTE-treated group than the control flies. However, BTE
      exerted a minimal effect on the expression of SOD2 and MTH genes. Dietary fat
      could induce oxidative stress and shorten the maximum lifespan to 15days, while
      addition of 10mg/ml BTE into diet extended it to 28days. Paraquat and H(2)O(2)
      challenge tests demonstrated that BTE prolonged the survival time only for Oregon
      R wild type flies but not for SOD(n108) or Cat(n1) mutants. This suggests that
      the lifespan-prolonging activity of BTE is mediated at least in part through SOD
      and CAT.

PMID- 19770033
TI  - Elucidating ANTs in worms using genomic and bioinformatic tools--biotechnological
      prospects?
AB  - Adenine nucleotide translocators (ANTs) belong to the mitochondrial carrier
      family (MCF) of proteins. ATP production and consumption are tightly linked to
      ANTs, the kinetics of which have been proposed to play a key regulatory role in
      mitochondrial oxidative phosphorylation. ANTs are also recognized as a central
      component of the mitochondrial permeability transition pore associated with
      apoptosis. Although ANTs have been investigated in a range of vertebrates,
      including human, mouse and cattle, and invertebrates, such as Drosophila
      melanogaster (vinegar fly), Saccharomyces cerevisiae (yeast) and Caenorhabditis
      elegans (free-living nematode), there has been a void of information on these
      molecules for parasitic nematodes of socio-economic importance. Exploring ANTs in
      nematodes has the potential lead to a better understanding of their fundamental
      roles in key biological pathways and might provide an avenue for the
      identification of targets for the rational design of nematocidal drugs. In the
      present article, we describe the discovery of an ANT from Haemonchus contortus
      (one of the most economically important parasitic nematodes of sheep and goats),
      conduct a comparative analysis of key ANTs and their genes (particularly ant-1.1)
      in nematodes and other organisms, predict the functional roles utilizing a
      combined genomic-bioinformatic approach and propose ANTs and associated molecules
      as possible drug targets, with the potential for biotechnological outcomes.

PMID- 19770034
TI  - Inflammation and brain injury: acute cerebral ischaemia, peripheral and central
      inflammation.
AB  - Inflammation is a classical host defence response to infection and injury that
      has many beneficial effects. However, inappropriate (in time, place and
      magnitude) inflammation is increasingly implicated in diverse disease states, now
      including cancer, diabetes, obesity, atherosclerosis, heart disease and, most
      relevant here, CNS disease. A growing literature shows strong correlations
      between inflammatory status and the risk of cerebral ischaemia (CI, most commonly
      stroke), as well as with outcome from an ischaemic event. Intervention studies to
      demonstrate a causal link between inflammation and CI (or its consequences) are
      limited but are beginning to emerge, while experimental studies of CI have
      provided direct evidence that key inflammatory mediators (cytokines, chemokines
      and inflammatory cells) contribute directly to ischaemic brain injury. However,
      it remains to be determined what the relative importance of systemic (largely
      peripheral) versus CNS inflammation is in CI. Animal models in which CI is driven
      by a CNS intervention may not accurately reflect the clinical condition; stroke
      being typically induced by atherosclerosis or cardiac dysfunction, and hence
      current experimental paradigms may underestimate the contribution of peripheral
      inflammation. Experimental studies have already identified a number of potential
      anti-inflammatory therapeutic interventions that may limit ischaemic brain
      damage, some of which have been tested in early clinical trials with potentially
      promising results. However, a greater understanding of the contribution of
      inflammation to CI is still required, and this review highlights some of the key
      mechanism that may offer future therapeutic targets.

PMID- 19770035
TI  - Functional autoradiography and gene expression analysis applied to the
      characterization of the alpha2-adrenergic system in the chicken brain.
AB  - Here we report a functional autoradiographic study of [(35)S]GTPgammaS binding
      induced by alpha(2)-adrenoceptor activation in chicken brain tissue sections
      using both 10(-4)M UK 14304 (bromoxidine or brimonidine) and 10(-6)M epinephrine
      as alpha(2)-adrenoceptor agonists. Assays were performed using two different
      incubation buffers: glycylglycine or Tris-HCl. Changes in the [(35)S]GTPgammaS
      basal binding values were detected, and different [(35)S]GTPgammaS specific
      binding values were also obtained depending on the buffer used for each drug. The
      best results were obtained with epinephrine in Tris-HCl, with slightly higher
      stimulation values than the observed with UK 14304 in glycylglycine buffer. The
      effect of the addition of adenosine deaminase to the incubation buffer was also
      tested. This effect decreasing basal binding in chicken was very small when
      compared to mammals, according with differences found in adenosine 1 receptor
      expression levels. Structures presenting alpha(2)-adrenoceptor-mediated G(i/o)
      protein stimulation fitted with areas previously described as enriched in
      alpha(2)-adrenoceptors in chicken brain, and their homologous areas in mammals.
      These data confirm the specificity of the results and reinforce the implication
      of the alpha(2)-adrenoceptors in the function of these brain nuclei. On the other
      hand, the expression level of the different alpha(2)-adrenoceptor subtypes was
      tested with real-time PCR. Contrasting with the alpha(2)-adrenoceptor subtype
      distribution previously described with radioligand competition assays, where
      alpha(2A) was the predominant alpha(2)-adrenoceptor subtype (>/=75%); in the
      present work, the ratio of alpha(2A):alpha(2B/C) gene expression was lower than
      expected both in telencephalon, tectum opticum, and cerebellum.

PMID- 19770036
TI  - Making and working with hydrogen sulfide: The chemistry and generation of
      hydrogen sulfide in vitro and its measurement in vivo: a review.
AB  - Hydrogen sulfide is rapidly emerging as an important vasoactive mediator formed
      in health and disease. Its biological action is centered on its reactivity with
      heme-proteins and its ability to activate K(ATP) channels. Hydrogen sulfide is a
      signalling molecule of the inflammatory and nervous systems, and in particular
      the cardiovascular system where it regulates vascular tone, cardiac work, and
      exerts cardioprotection. This has led to an explosion of papers in which the role
      of hydrogen sulfide generated in vitro has been used to stimulate biological
      responses, and where a variety of methods have been used to measure the
      concentration of this compound in biological fluids. Understanding the chemistry
      and the inherent problems in the analytical techniques used to measure hydrogen
      sulfide concentrations is critical to our expanding knowledge on the biology of
      hydrogen sulfide. In this brief review we will cover the chemistry of hydrogen
      sulfide, including sources of hydrogen sulfide, its speciation at physiological
      pH, the susceptibility of sulfide to aerobic oxidation, and the methods used to
      measure hydrogen sulfide concentrations in solution, including biological fluids.
      We also give a brief overview of knockout animals and inhibition of the enzymes
      involved in the formation of hydrogen sulfide in vivo.

PMID- 19770037
TI  - Proteolysis in prokaryotes--from molecular machines to a systems perspective.

PMID- 19770038
TI  - Temperature-dependent proteolysis as a control element in Escherichia coli
      metabolism.
AB  - Escherichia coli can grow at a broad temperature range, from less than 20 degrees
      C up to 45 degrees C. An increase in temperature results in a major physiological
      change, as enzymes work faster but, on the other hand, proteins tend to unfold.
      Therefore, a shift-up in temperature results in the induction of several
      regulatory response mechanisms aimed at restoring balanced growth at the new
      temperature. One important mechanism involves temperature-dependent proteolysis,
      which constitutes a fast response to temperature shift-ups. Here we discuss the
      effect of proteolysis on protein synthesis, and the heat shock response.

PMID- 19770039
TI  - Identification of a polymorphic collagen-like protein in the crustacean bacteria
      Pasteuria ramosa.
AB  - Pasteuria ramosa is a spore-forming bacterium that infects Daphnia species.
      Previous results demonstrated a high specificity of host clone/parasite genotype
      interactions. Surface proteins of bacteria often play an important role in
      attachment to host cells prior to infection. We analyzed surface proteins of P.
      ramosa spores by two-dimensional gel electrophoresis. For the first time, we
      prove that two isolates selected for their differences in infectivity reveal few
      but clear-cut differences in protein patterns. Using internal sequencing and
      LC/MS/MS, we identified a collagen-like protein named Pcl1a (Pasteuria collagen
      like protein 1a). This protein, reconstructed with the help of Pasteuria genome
      sequences, contains three domains: a 75-amino-acid amino-terminal domain with a
      potential transmembrane helix domain, a central collagen-like region (CLR)
      containing Gly-Xaa-Yaa (GXY) repeats, and a 7-amino-acid carboxy-terminal domain.
      The CLR region is polymorphic among the two isolates with amino-acid
      substitutions and a variable number of GXY triplets. Collagen-like proteins are
      rare in prokaryotes, although they have been described in several pathogenic
      bacteria, including Bacillus cereus, Bacillus anthracis and Bacillus
      thuringiensis, closely related to Pasteuria species, in which they could be
      involved in the adherence of bacteria to host cells.

PMID- 19770040
TI  - Analysis of SDF-1/CXCR4 signaling in primordial germ cell migration and survival
      or differentiation in Xenopus laevis.
AB  - Directional migration of primordial germ cells (PGCs) toward future gonads is a
      common feature in many animals. In zebrafish, mouse and chicken, SDF-1/CXCR4
      chemokine signaling has been shown to have an important role in PGC migration. In
      Xenopus, SDF-1 is expressed in several regions in embryos including dorsal
      mesoderm, the target region that PGCs migrate to. CXCR4 is known to be expressed
      in PGCs. This relationship is consistent with that of more well-known animals.
      Here, we present experiments that examine whether chemokine signaling is involved
      in PGC migration of Xenopus. We investigate: (1) Whether injection of antisense
      morpholino oligos (MOs) for CXCR4 mRNA into vegetal blastomere containing the
      germ plasm or the precursor of PGCs disturbs the migration of PGCs? (2) Whether
      injection of exogenous CXCR4 mRNA together with MOs can restore the knockdown
      phenotype? (3) Whether the migratory behavior of PGCs is disturbed by the
      specific expression of mutant CXCR4 mRNA or SDF-1 mRNA in PGCs? We find that the
      knockdown of CXCR4 or the expression of mutant CXCR4 in PGCs leads to a decrease
      in the PGC number of the genital ridges, and that the ectopic expression of SDF-1
      in PGCs leads to a decrease in the PGC number of the genital ridges and an
      increase in the ectopic PGC number. These results suggest that SDF-1/CXCR4
      chemokine signaling is involved in the migration and survival or in the
      differentiation of PGCs in Xenopus.

PMID- 19770041
TI  - Identification of heavy metal regulated genes from the root associated ascomycete
      Cadophora finlandica using a genomic microarray.
AB  - The ascomycete Cadophora finlandica, which can form mycorrhizas with
      ectomycorrhizal and ericoid hosts, is commonly found in heavy metal polluted
      soils. To understand the selective advantage of this organism at contaminated
      sites heavy metal regulated genes from C. finlandica were investigated. For gene
      identification a strategy based on a genomic microarray was chosen, which allows
      a rapid, genome-wide screening in genetically poorly characterized organisms. In
      a preliminary screen eleven plasmids covering eight distinct genomic regions and
      encoding a total of ten Cd-regulated genes were identified. Northern analyses
      with RNA from C. finlandica grown in the presence of either Cd, Pb or Zn revealed
      different transcription patterns in response to the heavy metals present in the
      growth medium. The Cd-regulated genes are predicted to encode several
      extracellular proteins with unknown functions, transporters, a centaurin-type
      regulator of intracellular membrane trafficking, a GNAT-family acetyltransferase
      and a B-type cyclin.

PMID- 19770042
TI  - Reduced VGLUT2 expression increases motor neuron viability in Sod1(G93A) mice.
AB  - Glutamate-induced excitotoxicity has been suggested to influence pathogenesis in
      amyotrophic lateral sclerosis (ALS). Vesicular glutamate transporters (VGLUTs)
      are responsible for transport of glutamate into synaptic vesicles. Nerve
      terminals that envelop motor neurons in the spinal cord contain VGLUT2 and are
      likely responsible for most glutamate release on motor neurons. The role of
      VGLUT2 in ALS and its potential role to influence motor neuron survival have not
      previously been studied. Here, in a mouse model of ALS, we show that genetic
      reduction of VGLUT2 protein levels rescues motor neurons in the lumbar spinal
      cord and in the brainstem as well as neuromuscular junctions in tibialis
      anterior. Although the number of remaining motor neurons increased, neither
      disease onset nor life span was affected. We also show that the motor neuron
      subpopulation-specific markers calcitonin/calcitonin-related polypeptide alpha
      (Calca) and estrogen related receptor beta (ERRbeta) respond in a similar way to
      reduced VGLUT2 as the whole motor neuron population suggesting that the rescued
      motor neurons are not of a particular motor unit type. Taken together, this
      suggests that reduced levels of VGLUT2 decrease motor neuron degeneration but do
      not prevent loss of motor neuron function in the SOD1(G93A) mouse model for ALS.

PMID- 19770044
TI  - Experience, cortical remapping, and recovery in brain disease.
AB  - Recovery of motor function in brain and spinal cord disorders is an area of
      active research that seeks to maximize improvement after an episode of neuronal
      death or dysfunction. Recovery likely results from changes in structure and
      function of undamaged neurons, and this plasticity is a target for rehabilitative
      strategies. Sensory and motor function are mapped onto brain regions
      somatotopically, and these maps have been demonstrated to change in response to
      experience, particularly in development, but also in adults after injury. The map
      concept, while appealing, is limited, as the fine structure of the motor
      representation is not well-ordered somatotopically. But after stroke, the spared
      areas of the main cortical map for movement appear to participate in representing
      affected body parts, expanding representation in an experience-dependent manner.
      This occurs in both animal models and human clinical trials, although one must be
      cautious in comparing the results of invasive electrophysiological techniques
      with non-invasive ones such as transcranial magnetic stimulation. Developmental
      brain disorders, such as cerebral palsy, and embryonic abnormalities, such as
      dysmelia, demonstrate the potential of the human brain to remap the motor system.
      Future therapies may be able to use that potential to maximize recovery.

PMID- 19770046
TI  - Investigating association of brain volumes with intracranial capacity in
      schizophrenia.
AB  - Intracranial volume (ICV) is usually treated as a global or nuisance covariate in
      almost all volumetric studies of schizophrenia. However, validation for this
      analytic method has seldom been accomplished. In this study, we aimed to
      determine the effects of ICV on gray matter (GM) and white matter (WM) volumes.
      Sixty-three patients with schizophrenia and sixty normal controls were recruited;
      and high resolution T1 weighted images were obtained by 3T-MRI. After
      segmentation and normalization of the images into GM, WM, and cerebrospinal fluid
      (CSF), multiple regression analyses of global GM and WM volumes were performed
      using explanatory variables such as diagnosis, ICV, and diagnosis-ICV
      interaction. In addition, associations between regional GM and WM volumes with
      ICV were also investigated using voxel-based morphometry (VBM). No significant
      interaction between diagnosis and ICV was found for global GM volume, whereas
      interactions were detected in restricted GM areas using VBM. On the other hand,
      an interaction between ICV and diagnosis was found in WM not only for regional
      volumes, but also for global WM volume. The regression slope of global WM volumes
      against ICV was steeper in patients with schizophrenia than in healthy controls.
      These results imply that ICV should be carefully evaluated in the analyses of
      volumetric studies of schizophrenia, especially when analyzing WM volumes.

PMID- 19770045
TI  - Why do children make mirror errors in reading? Neural correlates of mirror
      invariance in the visual word form area.
AB  - Young children often make mirror errors when learning to read and write, for
      instance writing their first name from right to left in English. This competence
      vanishes in most adult readers, who typically cannot read mirror words but retain
      a strong competence for mirror recognition of images. We used fast behavioral and
      fMRI repetition priming to probe the brain mechanisms underlying mirror
      generalization and its absence for words in adult readers. In two groups of
      French and Japanese readers, we show that the left fusiform visual word form
      area, a major site of learning during reading acquisition, simultaneously shows a
      maximal effect of mirror priming for pictures and an absence of mirror priming
      for words. Thus, learning to read recruits an area which possesses a property of
      mirror invariance, seemingly present in all primates, which is deleterious for
      letter recognition and may explain children's transient mirror errors.

PMID- 19770043
TI  - Translating the frontiers of brain repair to treatments: starting not to break
      the rules.
AB  - The field of neural repair in stroke has identified cellular systems of
      reorganization and possible molecular mechanisms. Conceptual barriers now limit
      the generation of clinically useful agents. First, it is not clear what the
      causal mechanisms of neural repair are in stroke. Second, adequate delivery
      systems for neural repair drugs need to be determined for candidate molecules.
      Third, ad hoc applications of existing pharmacological agents that enhance
      attention, mood or arousal to stroke have failed. New approaches that
      specifically harness the molecular systems of learning and memory provide a new
      avenue for stroke repair drugs. Fourth, combinatorial treatments for neural
      repair need to be considered for clinical therapies. Finally, neural repair
      therapies have as a goal altering brain connections, cognitive maps and active
      neural networks. These actions may trigger a unique set of "neural repair side
      effects" that need to be considered in planning clinical trials.

PMID- 19770047
TI  - Having a word with yourself: neural correlates of self-criticism and self
      reassurance.
AB  - Self-criticism is strongly correlated with a range of psychopathologies, such as
      depression, eating disorders and anxiety. In contrast, self-reassurance is
      inversely associated with such psychopathologies. Despite the importance of self
      judgements and evaluations, little is known about the neurophysiology of these
      internal processes. The current study therefore used a novel fMRI task to
      investigate the neuronal correlates of self-criticism and self-reassurance.
      Participants were presented statements describing two types of scenario, with the
      instruction to either imagine being self-critical or self-reassuring in that
      situation. One scenario type focused on a personal setback, mistake or failure,
      which would elicit negative emotions, whilst the second was of a matched neutral
      event. Self-criticism was associated with activity in lateral prefrontal cortex
      (PFC) regions and dorsal anterior cingulate (dAC), therefore linking self
      critical thinking to error processing and resolution, and also behavioural
      inhibition. Self-reassurance was associated with left temporal pole and insula
      activation, suggesting that efforts to be self-reassuring engage similar regions
      to expressing compassion and empathy towards others. Additionally, we found a
      dorsal/ventral PFC divide between an individual's tendency to be self-critical or
      self-reassuring. Using multiple regression analyses, dorsolateral PFC activity
      was positively correlated with high levels of self-criticism (assessed via self
      report measure), suggesting greater error processing and behavioural inhibition
      in such individuals. Ventrolateral PFC activity was positively correlated with
      high self-reassurance. Our findings may have implications for the neural basis of
      a range of mood disorders that are characterised by a preoccupation with personal
      mistakes and failures, and a self-critical response to such events.

PMID- 19770048
TI  - General indices to characterize the electrical response of the cerebral cortex to
      TMS.
AB  - Transcranial magnetic stimulation (TMS) combined with simultaneous high-density
      electroencephalography (hd-EEG) represents a straightforward way to gauge
      cortical excitability and connectivity in humans. However, the analysis,
      classification and interpretation of TMS-evoked potentials are hampered by scarce
      a priori knowledge about the physiological effect of TMS and by lack of an
      established data analysis framework. Here, we implemented a standardized, data
      driven procedure to characterize the electrical response of the cerebral cortex
      to TMS by means of three synthetic indices: significant current density (SCD),
      phase-locking (PL) and significant current scattering (SCS). SCD sums up the
      amplitude of all significant currents induced by TMS, PL reflects the ability of
      TMS to reset the phase of ongoing cortical oscillations, while SCS measures the
      average distance of significantly activated sources from the site of stimulation.
      These indices are aimed at capturing different aspects of brain responsiveness,
      ranging from global cortical excitability towards global cortical connectivity.
      We analyzed the EEG responses to TMS of Brodmann's area 19 at increasing
      intensities in five healthy subjects. The spatial distribution and time course of
      SCD, PL and SCS revealed a reproducible profile of excitability and connectivity,
      characterized by a local activation threshold around a TMS-induced electric field
      of 50 V/m and by a selective propagation of TMS-evoked activation from occipital
      to ipsilateral frontal areas that reached a maximum at 70-100 ms. These general
      indices may be used to characterize the effects of TMS on any cortical area and
      to quantitatively evaluate cortical excitability and connectivity in
      physiological and pathological conditions.

PMID- 19770049
TI  - Dynamic causal modeling and Granger causality Comments on: the identification of
      interacting networks in the brain using fMRI: model selection, causality and
      deconvolution.

PMID- 19770050
TI  - Differential role of anterior prefrontal and premotor cortex in the processing of
      relational information.
AB  - Processing of relational information is a prerequisite underlying a number of
      higher cognitive faculties. Different brain regions within the frontal cortex
      have been implicated in supporting this function. The present study aimed at
      differentiating the roles of two frontal areas - anterior prefrontal cortex
      (aPFC) and premotor cortex (PMC) - in relational information processing using
      functional magnetic resonance imaging (fMRI). We tested the assumptions that PMC
      and aPFC differ as to their respective roles (1) in concrete (action-related)
      versus abstract relational information processing and (2) in concatenation versus
      integration of relational information. A reasoning paradigm adapted from Raven's
      Progressive Matrices was employed, manipulating the number and type of rules
      governing the matrices and creating an "abstract" and an "action" condition.
      Results suggest that PMC and aPFC are functionally differentiated by the type,
      not by the domain of relational processing, with PMC engaged in the sequential
      concatenation of relations, and aPFC in their integration. These results support
      hierarchical models of frontal function, while challenging the postulate of
      domain-specific processing within the frontal lobes.

PMID- 19770051
TI  - 3D mapping of somatotopic reorganization with small animal functional MRI.
AB  - There are few in vivo noninvasive methods to study neuroplasticity in animal
      brains. Functional MRI (fMRI) has been developed for animal brain mapping, but
      few fMRI studies have analyzed functional alteration due to plasticity in animal
      models. One major limitation is that fMRI maps are characterized by statistical
      parametric mapping making the apparent boundary dependent on the statistical
      threshold used. Here, we developed a method to characterize the location of
      center-of-mass in fMRI maps that is shown not to be sensitive to statistical
      threshold. Utilizing centers-of-mass as anchor points to fit the spatial
      distribution of the BOLD response enabled quantitative group analysis of altered
      boundaries of functional somatosensory maps. This approach was used to study
      cortical reorganization in the rat primary somatosensory cortex (S1) after
      sensory deprivation to the barrel cortex by follicle ablation (F.A.). FMRI
      demonstrated an enlarged nose S1 representation in the 3D somatotopic functional
      maps. This result clearly demonstrates that fMRI enables the spatial mapping of
      functional changes that can characterize multiple regions of S1 cortex and still
      be sensitive to changes due to plasticity.

PMID- 19770052
TI  - Three stages of facial expression processing: ERP study with rapid serial visual
      presentation.
AB  - Electrophysiological correlates of the processing facial expressions were
      investigated in subjects performing the rapid serial visual presentation (RSVP)
      task. The peak latencies of the event-related potential (ERP) components P1,
      vertex positive potential (VPP), and N170 were 165, 240, and 240 ms,
      respectively. The early anterior N100 and posterior P1 amplitudes elicited by
      fearful faces were larger than those elicited by happy or neutral faces, a
      finding which is consistent with the presence of a 'negativity bias.' The
      amplitude of the anterior VPP was larger when subjects were processing fearful
      and happy faces than when they were processing neutral faces; it was similar in
      response to fearful and happy faces. The late N300 and P300 not only
      distinguished emotional faces from neutral faces but also differentiated between
      fearful and happy expressions in lag2. The amplitudes of the N100, VPP, N170,
      N300, and P300 components and the latency of the P1 component were modulated by
      attentional resources. Deficient attentional resources resulted in decreased
      amplitude and increased latency of ERP components. In light of these results, we
      present a hypothetical model involving three stages of facial expression
      processing.

PMID- 19770053
TI  - Finding meaning in novel geometric shapes influences electrophysiological
      correlates of repetition and dissociates perceptual and conceptual priming.
AB  - Repeatedly viewing an object can engender fluency-related implicit memory for
      perceptual and conceptual attributes, as indexed in tests of perceptual and
      conceptual priming, respectively. Stimuli with minimal pre-experimental meaning
      allow direct comparisons between these two types of priming and explorations of
      whether corresponding neural mechanisms differ. We therefore examined
      electrophysiological correlates of perceptual and conceptual priming for
      minimalist geometric shapes (squiggles). Response time measures of conceptual
      priming were evident for squiggles rated by individual subjects as most
      meaningful, but not for those rated least meaningful. Conceptual-priming
      magnitude was proportional across individuals to the amplitude of FN400 brain
      potentials, but only for meaningful squiggles. Perceptual priming was evident for
      squiggles irrespective of meaningfulness, and perceptual-priming magnitude was
      proportional to the amplitude of frontal P170 potentials. These findings
      therefore show that a single exposure to a novel stimulus can lead to neural
      processing accompanying conceptual priming that is distinct from that
      accompanying perceptual priming (FN400 potentials vs. P170 potentials,
      respectively). Overall, this evidence is also relevant to the current debate over
      the neural correlates of familiarity-based recognition, and runs counter to the
      prominent supposition that familiarity can be generically indexed by FN400
      potentials.

PMID- 19770054
TI  - Structural and functional brain correlates of subclinical psychotic symptoms in
      11-13 year old schoolchildren.
AB  - Studying children experiencing psychotic symptoms provides a unique opportunity
      to examine the vulnerability to psychosis within the context of development.
      Using neuroimaging techniques this study investigated cognitive control
      functions, brain volumetrics and white matter integrity in an at-risk cohort of
      children. Between-subjects assessment of brain function and structure among 11
      school-going, non-treatment seeking children aged 11-13 who were at symptomatic
      risk for psychosis (AR) and 14 healthy control children aged 11-12 without
      subclinical psychotic symptoms (CON). MRI assessments included functional
      measures of response inhibition and error-related processes, whole brain voxel
      based morphometry (VBM) of gray matter (GM) and diffusion tensor imaging (DTI)
      utilizing fractional anisotropy to probe white matter (WM) integrity. fMRI
      results showed reduced activity in the AR group within right frontal and
      bilateral temporal cortex for response inhibition and reduced activity within the
      anterior cingulate, insula and middle frontal gyrus for error-related processing
      (p<.05, corrected). VBM analysis revealed GM increases in the AR group within
      middle and superior temporal gyri, angular gyrus, orbitofrontal gyrus and GM
      decrease within the inferior temporal gyrus (p<.05, corrected). DTI analysis
      identified WM decreases in the AR group along the inferior fronto-occipital
      fasciculus, cingulum and inferior longitudinal fasciculus (p<.05, corrected).
      This multimodal investigation revealed aberrant prefrontal-temporal dysfunction
      in addition to cingulate and insular dysfunctions which provide potential early
      neurocognitive risk markers related to the susceptibility for developing
      psychosis and subsequently the neurodevelopmental trajectory leading to
      schizophrenia.

PMID- 19770055
TI  - Differential effects of global and cerebellar normalization on detection and
      differentiation of dementia in FDG-PET studies.
AB  - FDG-PET ([18F]fluorodeoxyglucose positron emission tomography) is frequently used
      to improve the differential diagnosis of dementia. However, a fundamental
      methodological issue of the reference area for the intensity normalization
      procedure is still unsolved. Here, we systematically compared the two most
      commonly used normalization methods to the cerebral and to the cerebellar
      metabolic rate for glucose with regard to detection and differentiation of
      dementia syndromes. FDG-PET imaging was performed on 19 subjects with early
      Alzheimer's disease, 13 subjects with early frontotemporal lobar degeneration and
      10 subjects complaining of memory impairment, which had not been confirmed by
      comprehensive clinical testing. Images were normalized to either the cerebral or
      the cerebellar metabolic rate for glucose. Differences in relative regional
      glucose metabolism were assessed by voxelwise comparison. Analysis using the two
      normalization procedures revealed remarkable differential effects. Whereas
      cerebellar normalization was superior in identifying dementia patients in
      comparison to control subjects, cerebral normalization showed better results for
      differential diagnosis between types of dementia. These effects were shown for
      both, Alzheimer's disease and frontotemporal lobar degeneration. Relative
      hypermetabolism in comparison to the control group was only detected in both
      kinds of dementia using global normalization. The results indicate that
      normalization has a decisive impact on diagnostic accuracy in dementia. While
      cerebellar normalization seems to be more sensitive for early diagnosis, cerebral
      global normalization might be superior for differential diagnostic purposes in
      dementia syndromes.

PMID- 19770056
TI  - Neural reward processing is modulated by approach- and avoidance-related
      personality traits.
AB  - The neural processing of reward can be differentiated into two sub-components
      with different functions, "wanting" (i.e., the expectation of a reward which
      includes appetitive and motivational components) and "liking" (i.e., the hedonic
      impact experienced during the receipt of a reward), involving distinct neural
      systems. We hypothesize that variability in neural reward processing previously
      observed in healthy subjects could reflect inter-individual differences in
      personality. Therefore, the aim of this study was to investigate how the neural
      processing during expectation and reception of a reward depends on interpersonal
      differences in reward sensitivity, more specifically the tendency to approach vs.
      avoid reward-related situations. We employed event-related functional magnetic
      resonance imaging during a monetary incentive delay task. Subjects with a high
      approach motivation showed more activation of the Ventral Striatum (VS) during
      the receipt of a reward, and more medial orbitofrontal activity during both the
      receipt and omission of a reward. Subjects with a high behavioral inhibition
      showed less activation in the VS during the receipt of a reward. These findings
      indicate that the tendency to approach or avoid reward-related situations
      exhibits a distinct relation with neural reward processing. Specifically,
      subjects with high behavioral approach appear to be sensitive mainly to positive
      outcomes and to a lesser extent to the omissions of rewards, whereas subjects
      with low behavioral approach as well as those with a high inhibition tendency
      display a blunted response to rewards.

PMID- 19770058
TI  - Motivational orientation modulates the neural response to reward.
AB  - Motivational orientation defines the source of motivation for an individual to
      perform a particular action and can either originate from internal desires (e.g.,
      interest) or external compensation (e.g., money). To this end, motivational
      orientation should influence the way positive or negative feedback is processed
      during learning situations and this might in turn have an impact on the learning
      process. In the present study, we thus investigated whether motivational
      orientation, i.e., extrinsic and intrinsic motivation modulates the neural
      response to reward and punishment as well as learning from reward and punishment
      in 33 healthy individuals. To assess neural responses to reward, punishment and
      learning of reward contingencies we employed a probabilistic reversal learning
      task during functional magnetic resonance imaging. Extrinsic and intrinsic
      motivation were assessed with a self-report questionnaire. Rewarding trials
      fostered activation in the medial orbitofrontal cortex and anterior cingulate
      gyrus (ACC) as well as the amygdala and nucleus accumbens, whereas for punishment
      an increased neural response was observed in the medial and inferior prefrontal
      cortex, the superior parietal cortex and the insula. High extrinsic motivation
      was positively correlated to increased neural responses to reward in the ACC,
      amygdala and putamen, whereas a negative relationship between intrinsic
      motivation and brain activation in these brain regions was observed. These
      findings show that motivational orientation indeed modulates the responsiveness
      to reward delivery in major components of the human reward system and therefore
      extends previous results showing a significant influence of individual
      differences in reward-related personality traits on the neural processing of
      reward.

PMID- 19770057
TI  - Gait disturbance associated with white matter changes: a gait analysis and blood
      flow study.
AB  - To clarify the mechanisms underlying gait disturbance secondary to age-related
      white matter changes (ARWMC), cerebral perfusion was investigated during
      treadmill walking. Twenty subjects with extensive hyperintensities in the
      periventricular and deep white matter on T(2)-weighted magnetic resonance images
      (MRI) were recruited. The ARWMC subjects were classified into gait-disturbed (GD)
      and non-GD groups according to clinical criteria. All the subjects underwent gait
      analyses and cerebral perfusion measurements during both gait and rest by using
      single photon emission computed tomography. The GD group showed greater double
      support time/phase and stride width, and slower walking velocity, than the non-GD
      group. In an analysis of pooled data from all the subjects, gait-induced
      increases in cerebral perfusion were observed in the supplementary motor areas
      (SMA), lateral premotor cortex (PMC), primary motor and somatosensory areas,
      visual areas, basal ganglia and cerebellum. A between-group comparison of gait
      induced perfusion changes showed relative underactivation of the SMA, thalamus
      and basal ganglia, together with relative overactivation of the PMC, in the GD
      group compared with the non-GD group. In a separate correlation analysis
      including all the subjects, as the double support phase was longer (that was,
      gait disturbance was more severe), the gait-induced perfusion changes were
      proportionally reduced in the SMA, visual cortex, and thalamus. The present study
      suggests that abnormalities in the basal ganglia-thalamo-cortical loops partly
      explain gait disturbance observed in a subset of subjects with ARWMC.

PMID- 19770059
TI  - Brain networks involved in haptic and visual identification of facial expressions
      of emotion: an fMRI study.
AB  - Previous neurophysiological and neuroimaging studies have shown that a cortical
      network involving the inferior frontal gyrus (IFG), inferior parietal lobe (IPL)
      and cortical areas in and around the posterior superior temporal sulcus (pSTS)
      region is employed in action understanding by vision and audition. However, the
      brain regions that are involved in action understanding by touch are unknown.
      Lederman et al. (2007) recently demonstrated that humans can haptically recognize
      facial expressions of emotion (FEE) surprisingly well. Here, we report a
      functional magnetic resonance imaging (fMRI) study in which we test the
      hypothesis that the IFG, IPL and pSTS regions are involved in haptic, as well as
      visual, FEE identification. Twenty subjects haptically or visually identified
      facemasks with three different FEEs (disgust, neutral and happiness) and casts of
      shoes (shoes) of three different types. The left posterior middle temporal gyrus,
      IPL, IFG and bilateral precentral gyrus were activated by FEE identification
      relative to that of shoes, regardless of sensory modality. By contrast, an
      inferomedial part of the left superior parietal lobule was activated by haptic,
      but not visual, FEE identification. Other brain regions, including the lingual
      gyrus and superior frontal gyrus, were activated by visual identification of
      FEEs, relative to haptic identification of FEEs. These results suggest that
      haptic and visual FEE identification rely on distinct but overlapping neural
      substrates including the IFG, IPL and pSTS region.

PMID- 19770060
TI  - Congenital disorders of ribosome biogenesis and bone marrow failure.
AB  - Diamond Blackfan anemia (DBA) is a congenital bone marrow (BM) failure syndrome
      that typically results in macrocytic anemia within the first year of life. DBA is
      also associated with birth defects, increased incidence of cancer, and other
      cytopenias. Shwachman-Diamond syndrome (SDS) is a multisystem disease
      characterized by exocrine pancreatic dysfunction, impaired hematopoiesis, and
      leukemia predisposition. Other clinical features include skeletal, immunologic,
      hepatic, and cardiac disorders. Treatment for these BM failure syndromes,
      including stem cell transplantation (SCT), will be discussed in this review.

PMID- 19770061
TI  - Signaling pathways maintaining stem cells at the plant shoot apex.
AB  - The above ground organs of plants are generated by the shoot apical meristem.
      Cellular characteristics and molecular markers indicate that the shoot meristem
      is patterned into domains with different functions, with stem cells residing in
      the outer three cell layers of the central zone of the meristem. The boundaries
      of the domains are determined by positional signals. Here we will discuss our
      current understanding of the signaling network involved in determining stem cell
      fate and in setting the boundaries of the stem cell niche at the plant shoot
      apex.

PMID- 19770062
TI  - Control of division and differentiation of plant stem cells and their
      derivatives.
AB  - The core mechanism of the plant cell cycle is conserved with all other eukaryotes
      but several aspects are unique to plant cells. Key characteristics of plant
      development include indeterminate growth and repetitive organogenesis derived
      from stem cell pools and they may explain the existence of the high number of
      cell cycle regulators in plants. In this review, we give an overview of the plant
      cell cycle and its regulatory components. Furthermore, we discuss the cell cycle
      aspects of plant stem cell maintenance and how the cell cycle relates to cellular
      differentiation during development. We exemplify this transition by focusing on
      organ initiation in the shoot.

PMID- 19770063
TI  - Stem cell function during plant vascular development.
AB  - While many regulatory mechanisms controlling the development and function of root
      and shoot apical meristems have been revealed, our knowledge of similar processes
      in lateral meristems, including the vascular cambium, is still limited. Our
      understanding of even the anatomy and development of lateral meristems
      (procambium or vascular cambium) is still relatively incomplete, let alone their
      genetic regulation. Research into this particular tissue type has been mostly
      hindered by a lack of suitable molecular markers, as well as the fact that thus
      far very few mutants affecting plant secondary development have been described.
      The development of suitable molecular markers is a high priority in order to help
      define the anatomy, especially the location and identity of cambial stem cells
      and the developmental phases and molecular regulatory mechanisms of the cambial
      zone. To date, most of the advances have been obtained by studying the role of
      the major plant hormones in vascular development. Thus far auxin, cytokinin,
      gibberellin and ethylene have been implicated in regulating the maintenance and
      activity of cambial stem cells; the most logical question in research would be
      how these hormones interact during the various phases of cambial development.

PMID- 19770065
TI  - Aspergillus oryzae atfA controls conidial germination and stress tolerance.
AB  - We compared atfA and atfB, the genes encoding the respective ATF/CREB-type
      transcription factors in Aspergillus oryzae. The germination ratio of DeltaatfA
      conidia was low without any stress, unlike that of DeltaatfB conidia. The
      DeltaatfA conidia were more sensitive to oxidative stress than the DeltaatfB
      conidia, which are also sensitive to oxidative stress. We compared the gene
      expressions of these strains by using a DNA microarray, GeneChip. Almost all the
      genes regulated by atfB were also regulated by atfA, but atfA also regulated many
      genes that were not regulated by atfB, including some genes putatively involved
      in oxidative stress resistance. The level of glutamate, the major amino acid in
      A. oryzae conidia, was significantly low only in the DeltaatfA conidia, and the
      glycerol accumulation during germination was not observed only in the DeltaatfA
      strain. We therefore concluded that atfA is involved in germination via carbon
      and nitrogen source metabolism.

PMID- 19770064
TI  - Fungal echinocandin resistance.
AB  - The echinocandins are the newest class of antifungal agents in the clinical
      armory. These secondary metabolites are non-competitive inhibitors of the
      synthesis of beta-(1,3)-glucan, a major structural component of the fungal cell
      wall. Recent work has shown that spontaneous mutations can arise in two hot spot
      regions of Fks1 the target protein of echinocandins that reduce the enzyme's
      sensitivity to the drug. However, other strains have been isolated in which the
      sequence of FKS1 is unaltered yet the fungus has decreased sensitivity to
      echinocandins. In addition it has been shown that echinocandin-treatment can
      induce cell wall salvage mechanisms that result in the compensatory upregulation
      of chitin synthesis in the cell wall. This salvage mechanism strengthens cell
      walls damaged by exposure to echinocandins. Therefore, fungal resistance to
      echinocandins can arise due to the selection of either stable mutational or
      reversible physiological alterations that decrease susceptibility to these
      antifungal agents.

PMID- 19770067
TI  - Structural characterization of hemoglobins from Monilifera and Frenulata
      tubeworms (Siboglinids): first discovery of giant hexagonal-bilayer hemoglobin in
      the former "Pogonophora" group.
AB  - Siboglinids are symbiotic polychete annelids having hemoglobins as essential
      oxygen- and sulfide-carriers for their endosymbiotic bacteria. We analyzed the
      structure of the hemoglobins from two species of siboglinids: the monilifera
      Sclerolinum contortum and the frenulata Oligobrachia webbi (i.e.
      haakonmosbiensis) from Norwegian cold seeps. Measured by Multi-Angle Laser Light
      Scattering (MALLS), Sclerolinum shows a 3190+/-50 kDa hexagonal bilayer
      hemoglobin (HBL-Hb) and a 461+/-46 kDa ring-Hb, just as vestimentifera, whereas
      Oligobrachia has a 409+/-3.7 kDa ring-Hb only. Electrospray Ionization-Mass
      Spectrometry (ESI-MS) showed Sclerolinum HBL-Hb composed of seven monomeric
      globins (15-16 kDa), three disulfide-bonded globin heterodimers and three
      linkers. The heterodimers always contain globin-b (15814.4+/-1.5 Da). Sclerolinum
      ring-Hb is composed of globins and dimers with identical masses as its HBL-Hb,
      but lacks linkers. Oligobrachia ring-Hb has three globin monomers (14-15 kDa)
      only, with no disulfide-bonded dimers. Comparison of Sclerolinum hemoglobins
      between Storegga and Haakon Mosby Mud Volcano, using the normalized height of
      deconvoluted ESI-MS peaks, shows differences in globin monomers abundances that
      could reflect genetic differences or differential gene expression between
      distinct seep populations. The discovery of HBL-Hb in Sclerolinum is a new
      element supporting the hypothesis of monilifera being phylogenetically more
      closely related to vestimentifera, than to frenulata.

PMID- 19770068
TI  - Role of HIV-1 Nef protein for virus replication in vitro.
AB  - The Nef protein of primate lentiviruses (simian and human immunodeficiency
      viruses; SIV/HIVs) appears to be multi-functional and plays a pivotal role in
      viral persistence and pathogenesis in vivo. Of its numerous functions reported to
      date, the ability to enhance virion infectivity in indicator cell lines and to
      augment viral replication in peripheral blood mononuclear cells (PBMCs) and
      lymphocytes (PBLs) is very well conserved among various SIV/HIVs. This review
      summarizes and organizes current knowledge of HIV-1 Nef with respect to this
      particularly virological activity for understanding the basis of its in vivo
      function.

PMID- 19770069
TI  - Silencing of tachyzoite enolase 2 alters nuclear targeting of bradyzoite enolase
      1 in Toxoplasma gondii.
AB  - In Toxoplasma gondii, an intracellular parasite of the phylum Apicomplexa, two
      isoforms of enolase (ENO1 and ENO2) are expressed in stage-specific manner. ENO2
      is expressed only in rapidly growing tachyzoites, while ENO1 is in slowly growing
      bradyzoites. Interestingly, the localization of ENO1 and ENO2 in the nuclear
      compartment has suggested possible roles of the proteins in gene regulation
      and/or cell cycle. To understand the physiological role of ENO2 in T. gondii, the
      expression of ENO2 was silenced using a homologous gene silencing procedure. The
      introduction or expression of ENO2 dsRNA successfully silenced the expression of
      ENO2 at the levels of transcripts and proteins. While there was no change in the
      growth rate of both tachyzoites and bradyzoites, a subtle phenotypic change was
      observed in the localization of the ENO1 gene product in the bradyzoite stage.

PMID- 19770066
TI  - The helix bundle: a reversible lipid binding motif.
AB  - Apolipoproteins are the protein components of lipoproteins that have the innate
      ability to inter convert between a lipid-free and a lipid-bound form in a facile
      manner, a remarkable property conferred by the helix bundle motif. Composed of a
      series of four or five amphipathic alpha-helices that fold to form a helix
      bundle, this motif allows the en face orientation of the hydrophobic faces of the
      alpha-helices in the protein interior in the lipid-free state. A conformational
      switch then permits helix-helix interactions to be substituted by helix-lipid
      interactions upon lipid binding interaction. This review compares the
      apolipoprotein high-resolution structures and the factors that trigger this
      switch in insect apolipophorin III and the mammalian apolipoproteins,
      apolipoprotein E and apolipoprotein A-I, pointing out the commonalities and key
      differences in the mode of lipid interaction. Further insights into the lipid
      bound conformation of apolipoproteins are required to fully understand their
      functional role under physiological conditions.

PMID- 19770070
TI  - Isolation and characterization of the thrombin-like enzyme from Cryptelytrops
      purpureomaculatus venom.
AB  - A thrombin-like enzyme, purpurase, was purified from the Cryptelytrops
      purpureomaculatus (mangrove pit viper) venom using high performance ion-exchange
      and gel filtration chromatography. The purified sample (termed purpurase) yielded
      a homogeneous band in SDS-polyacrylamide gel electrophoresis with a molecular
      weight of 35,000. The N-terminal sequence of purpurase was determined to be
      VVGGDECNINDHRSLVRIF and is homologous to many other venom thrombin-like enzymes.
      Purpurase exhibits both arginine ester hydrolase and amidase activities. Kinetic
      studies using tripeptide chromogenic anilide substrates showed that purpurase is
      not fastidious towards its substrate. The clotting times of fibrinogen by
      purpurase were concentration dependent, with optimum clotting activity at 3mg
      fibronogen/mL. The clotting activity by purpurase was in the following decreasing
      order: cat fibrinogen>human fibrinogen>dog fibrinogen>goat fibrinogen>>rabbit
      fibrinogen. Reversed-phase HPLC analysis of the products of action of purpurase
      on bovine fibrinogen showed that only fibrinopeptide A was released. Indirect
      ELISA studies showed that anti-purpurase cross-reacted strongly with venoms of
      most crotalid venoms, indicating the snake venom thrombin-like enzymes generally
      possess similar epitopes. In the more specific double-sandwich ELISA, however,
      anti-purpurase cross-reacted only with venoms of certain species of the
      Trimeresurus complex, and the results support the recent proposed taxonomy
      changes concerning the Trimeresurus complex.

PMID- 19770071
TI  - Expiratory flow-limitation and heliox breathing in resting and exercising COPD
      patients.
AB  - In 26 stable patients with chronic obstructive pulmonary disease, tidal
      expiratory flow-limitation (TEFL), inspiratory capacity, breathing pattern and
      dyspnea sensation were assessed during air and heliox (20% O(2) in He) breathing
      at rest and during exercise up to 2/3 maximal work rate. Breathing air, the 13
      patients with TEFL at rest remained flow-limited also during exercise, while 7 of
      the non-flow-limited patients became flow-limited; tidal volume increased more in
      non-flow-limited patients, whereas inspiratory capacity decreased in flow-limited
      and increased in the non-flow-limited patients. Heliox did not abolish flow
      limitation, had no effect on breathing pattern, reduced exercise dynamic
      hyperinflation in 25% of the flow-limited patients, depending on the degree of
      the dynamic hyperinflation on air, and lessened dyspnea sensation in all
      patients. Hence, the presence of TEFL has no systematic effects on the
      respiratory response to heliox, and the heliox-induced decrease of exercise
      dyspnea is not mainly due to changes in dynamic hyperinflation or TEFL.

PMID- 19770072
TI  - Early symptom-relief after valvulotomy in mitral stenosis indicates role of
      lobeline-sensitive intrapulmonary receptors.
AB  - Respiratory sensations of eight patients with mitral stenosis in response to i.v.
      lobeline and 6-min walk before percutaneous mitral valvulotomy (PMV) were 'being
      short of breath', pressure in chest, tracheo-bronchial irritation, a desire to
      cough, persistent dry cough, chest pain and were qualitatively similar amongst
      75% (P=0.005) of the patients. A week after PMV lobeline evoked similar
      sensations but the threshold dose decreased from 32.4+/-3.8 to 24.1+/-3.2
      microg/kg (P=0.001) and pulmonary artery wedge pressure (PAwP), signifying
      reduction in pulmonary congestion, from 23.1+/-1.4 to 14.3+/-3.4 mm Hg (P<0.001).
      Distance walked in 6 min increased from 217+/-58 to 319+/-51.6m; and mitral valve
      area from 0.63+/-0.01 to 1.43+/-0.26 cm(2) (P<0.001). A fall in lobeline
      sensation threshold dose indicated reduction in pulmonary congestion and stimulus
      to juxtapulmonary/J (or pulmonary C fibre) receptors which suggests that they had
      contributed to the respiratory and viscerosomatic symptoms seen before PMV.

PMID- 19770074
TI  - Disentangling hypoxia and hypobaria.

PMID- 19770075
TI  - Catalytic role of a conserved cysteine residue in the desulfonation reaction by
      the alkanesulfonate monooxygenase enzyme.
AB  - Detailed kinetic studies were performed in order to determine the role of the
      single cysteine residue in the desulfonation reaction catalyzed by SsuD. Mutation
      of the conserved cysteine at position 54 in SsuD to either serine or alanine had
      little effect on FMNH(2) binding. The k(cat)/K(m) value for the C54S SsuD variant
      increased 3-fold, whereas the k(cat)/K(m) value for C54A SsuD decreased 6-fold
      relative to wild-type SsuD. An initial fast phase was observed in kinetic traces
      obtained for the oxidation of flavin at 370 nm when FMNH(2) was mixed against
      C54S SsuD (k(obs), 111 s(-1)) in oxygenated buffer that was 10-fold faster than
      wild-type SsuD (k(obs), 12.9 s(-1)). However, there was no initial fast phase
      observed in similar kinetic traces obtained for C54A SsuD. This initial fast
      phase was previously assigned to the formation of the C4a-(hydro)peroxyflavin in
      studies with wild-type SsuD. There was no evidence for the formation of the C4a
      (hydro)peroxyflavin with either SsuD variant when octanesulfonate was included in
      rapid reaction kinetic studies, even at low octanesulfonate concentrations. The
      absence of any C4a-(hydro)peroxyflavin accumulation correlates with the increased
      catalytic activity of C54S SsuD. These results suggest that the conservative
      serine substitution is able to effectively take the place of cysteine in
      catalysis. Conversely, decreased accumulation of the C4a-(hydro)peroxyflavin
      intermediate with the C54A SsuD variant may be due to decreased activity. The
      data described suggest that Cys54 in SsuD may be either directly or indirectly
      involved in stabilizing the C4a-(hydro)peroxyflavin intermediate formed during
      catalysis through hydrogen bonding interactions.

PMID- 19770073
TI  - Optimal interaction of respiratory and thermal regulation at rest and during
      exercise: role of a serotonin-gated spinoparabrachial thermoafferent pathway.
AB  - Recent evidence indicates that the lateral parabrachial nucleus (LPBN) in
      dorsolateral pons is pivotal in mediating the feedback control of inspiratory
      drive by central chemoreceptor input and feedforward control of body temperature
      by cutaneous thermoreceptor input. The latter is subject to descending
      serotonergic inhibition which gates the transmission of ascending thermoafferent
      information from spinal dorsal horn to the LPBN. Here, a model is proposed which
      suggests that the LPBN may be important in balancing respiratory and thermal
      homeostasis, two conflicting goals that are heightened by environmental heat/cold
      stress or exercise where the effects of respiratory thermolysis become prominent.
      This optimization model of respiratory-thermoregulatory interaction is supported
      by a host of recent studies which demonstrate that animals with serotonin (5-HT)
      dysfunction at the spinal dorsal horn--due to 5-HT antagonism, genetic 5-HT
      defects or spinal cord injury--all display similar respiratory abnormalities that
      are consistent with hyperactivity of the spinoparabrachial thermoafferent (and
      pain) pathway.

PMID- 19770076
TI  - Substrate competitive GSK-3 inhibitors - strategy and implications.
AB  - Glycogen synthase kinase-3 (GSK-3) is a highly conserved protein serine/threonine
      kinase ubiquitously distributed in eukaryotes as a constitutively active enzyme.
      Abnormally high GSK-3 activity has been implicated in several pathological
      disorders, including diabetes and neuron degenerative and affective disorders.
      This led to the hypothesis that inhibition of GSK-3 may have therapeutic benefit.
      Most GSK-3 inhibitors developed so far compete with ATP and often show limited
      specificity. Our goal is to develop inhibitors that compete with GSK-3
      substrates, as this type of inhibitor is more specific and may be useful for
      clinical applications. We have employed computational, biochemical, and molecular
      analyses to gain in-depth understanding of GSK-3's substrate recognition. Here we
      argue that GSK-3 is a promising drug discovery target and describe the strategy
      and practice for developing specific substrate-competitive inhibitors of GSK-3.

PMID- 19770077
TI  - Density-property relationships in collagen-glycosaminoglycan scaffolds.
AB  - Collagen-glycosaminoglycan scaffolds for the regeneration of skin have previously
      been fabricated by freeze-drying a slurry containing a co-precipitate of collagen
      and glycosaminoglycan. The mechanical properties of the scaffold are low (e.g.
      the dry compressive Young's modulus is roughly 30kPa and the dry compressive
      strength is roughly 5kPa). There is interest in using these scaffolds for tendon
      and ligament regeneration where there is a need for improved mechanical
      properties. Previous attempts to increase the mechanical properties of the
      scaffold by increasing the solid volume fraction of the scaffolds were limited by
      the increasing viscosity of the slurry, making it more difficult to mix and
      giving inhomogeneous scaffolds. Our recent work on mineralized collagen
      glycosaminoglycan scaffolds used a vacuum filtration technique to increase the
      volume fraction of solids in the slurry, thereby increasing the density and
      mechanical properties of the scaffolds. In this work, we used this technique to
      fabricate collagen-glycosaminoglycan scaffolds with dry densities between 0.0076
      and 0.0311gcm(-3) and pore sizes between 250 and 350microm, values appropriate
      for soft tissue growth. The compressive Young's modulus and strength in the dry
      state increased from 32 to 127kPa and from 5 to 19kPa, respectively, with
      increasing density. The tensile Young's modulus in the dry state increased from
      295 to 3.1MPa with increasing density. Finally, we showed that the attachment of
      cells onto the scaffold was directly proportional to the specific surface area of
      the scaffold, which defines the total internal surface area per volume of
      scaffold.

PMID- 19770078
TI  - Novel borate glass/chitosan composite as a delivery vehicle for teicoplanin in
      the treatment of chronic osteomyelitis.
AB  - Composite materials composed of borate bioactive glass and chitosan (designated
      BGC) were investigated in vitro and in vivo as a new delivery system for
      teicoplanin in the treatment of chronic osteomyelitis induced by methicillin
      resistant Staphylococcus aureus (MRSA). In vitro, the release of teicoplanin from
      BGC pellets into phosphate-buffered saline (PBS), as well as its antibacterial
      activity, were determined. The compressive strength of the pellets was measured
      after specific immersion times, and the structure of the pellets was
      characterized using scanning electron microscopy and X-ray diffraction. In vivo,
      the tibial cavity of New Zealand White rabbits was injected with MRSA strain to
      induce chronic osteomyelitis, treated by debridement after 4weeks, implanted with
      teicoplanin-loaded BGC pellets (designated TBGC) or BGC pellets, or injected
      intravenously with teicoplanin. After 12weeks' implantation, the efficacy of the
      TBGC pellets for treating osteomyelitis was evaluated using hematological,
      radiological, microbiological and histological techniques. When immersed in PBS,
      the TBGC pellets provided a sustained release of teicoplanin, while the surface
      of the pellets was converted to hydroxyapatite (HA). In vivo, the best
      therapeutic effect was observed in animals implanted with TBGC pellets, resulting
      in significantly lower radiological and histological scores, a lower positive
      rate of MRSA culture, and an excellent bone defect repair, without local or
      systemic side effects. The results indicate that TBGC pellets are effective in
      treating chronic osteomyelitis by providing a sustained release of teicoplanin,
      in addition to participating in bone regeneration.

PMID- 19770079
TI  - A familial 593-kb microdeletion of 16p11.2 associated with mental retardation and
      hemivertebrae.
AB  - Through several large-scale screening studies for autism spectrum disorders
      (ASD), a common 593-kb interstitial deletion of 16p11.2 has been identified as
      one of the most common genomic disorders associated with ASD. In this study, a
      familial occurrence of the 16p11.2 deletion was identified in association with
      hemivertebrae. The proband was a 3-year-old boy who showed developmental delay,
      displayed hyperactive but not autistic behavior, and had hemivertebrae, rib
      anomalies, and inguinal hernia. Familial investigation revealed that his mother
      shared the same deletion. Under the hypothesis of the existence of an unmasked
      mutation in the deletion region, we analyzed the sequence of the T-box 6 gene
      (TBX6) included in the deletion region, but did not detect any mutation. This
      suggests that haploinsufficiency of TBX6 can lead to vertebral malformation in
      low penetrance.

PMID- 19770081
TI  - Likeness-based detection of sleep slow oscillations in normal and altered sleep
      conditions: application on low-density EEG recordings.
AB  - Sleep slow oscillation (SSO) is a common EEG pattern of spontaneous activity
      during nonrapid eye movement sleep. A new method for detecting SSOs is presented
      and compared to previous canonical methods. The main result of this research is
      that for the first time an extensive SSO analysis is applied to clinical EEG
      montages, based on low-density EEG recordings. The proposed method gives positive
      indications about its effectiveness also for altered sleep, extending the SSO
      analysis to extreme cases, and thus, opening a new front for investigating
      pathophysiological correlates of sleep disorders.

PMID- 19770080
TI  - Biotin is not a natural histone modification.
AB  - In addition to its role as the cofactor of biotin-dependent carboxylases, biotin
      has been demonstrated to have a role in cellular processes including
      transcription and gene silencing. Histones have been proposed to be modified by
      biotin in a site-specific manner, providing a pathway by which biotin acts as a
      regulatory molecule for gene expression. However, there is uncertainty whether
      biotin attachment to histones in vitro can be extrapolated to biotin as a native
      histone modification. We critically examined a number of methods used to detect
      biotin attachment on histones, including [(3)H]-biotin uptake, Western blot
      analysis of histones, and mass spectrometry of affinity purified histone
      fragments with the objective of determining if the in vivo occurrence of histone
      biotinylation could be conclusively established. We found for each of these
      methods that, while biotin could be readily detected on native carboxylases or
      histones biotinylated in vitro, biotin attachment on native histones could not be
      detected in cell cultures from various sources. We conclude that biotin is absent
      in native histones to a sensitivity of at least one part per 100,000, suggesting
      that the regulatory impact of biotin on gene expression must be through alternate
      mechanisms.

PMID- 19770082
TI  - A step toward identification of surgical actions in mastoidectomy.
AB  - Mastoidectomy is a core surgical procedure in otologic surgery. It is believed
      that the procedure is performed by different surgeons with some variability.
      However, it is also believed that all surgeons use a finite number of fundamental
      surgical actions to complete the procedure. To determine how a surgeon performs a
      mastoidectomy, we sought to identify the fundamental surgical actions [called
      action primitives (APs)] and determine the transition boundaries among those APs.
      Our motivation for this paper is both to delineate the APs necessary to complete
      a mastoidectomy and to optimize and potentially automate the surgical process. In
      this paper, we present a new approach to developing methods for parsing raw data
      (position and orientation of the surgical tool and end-effector force) into a
      sequence of surgical tasks. The overall objective is to de-construct the surgical
      procedure into a series of APs. This paper presents results from our initial
      investigation on detecting transition boundaries and identifying APs involved in
      mastoidectomy.

PMID- 19770083
TI  - Stiffness and damping in postural control increase with age.
AB  - Upright balance is believed to be maintained through active and passive
      mechanisms, both of which have been shown to be impacted by aging. A compensatory
      balance response often observed in older adults is increased co-contraction,
      which is generally assumed to enhance stability by increasing joint stiffness. We
      investigated the effect of aging on standing balance by fitting body sway data to
      a previously developed postural control model that includes active and passive
      stiffness and damping parameters. Ten young (24 +/- 3 years) and seven older (75
      +/- 5 years) adults were exposed during eyes-closed stance to perturbations
      consisting of lateral pseudorandom floor tilts. A least-square fit of the
      measured body sway data to the postural control model found significantly larger
      active stiffness and damping model parameters in the older adults. These
      differences remained significant even after normalizing to account for different
      body sizes between the young and older adult groups. An age effect was also found
      for the normalized passive stiffness, but not for the normalized passive damping
      parameter. This concurrent increase in active stiffness and damping was shown to
      be more stabilizing than an increase in stiffness alone, as assessed by
      oscillations in the postural control model impulse response.

PMID- 19770084
TI  - Transcranial ultrasonic therapy based on time reversal of acoustically induced
      cavitation bubble signature.
AB  - Brain treatment through the skull with high-intensity focused ultrasound can be
      achieved with multichannel arrays and adaptive focusing techniques such as time
      reversal. This method requires a reference signal to be either emitted by a real
      source embedded in brain tissues or computed from a virtual source, using the
      acoustic properties of the skull derived from computed tomography images. This
      noninvasive computational method focuses with precision, but suffers from
      modeling and repositioning errors that reduce the accessible acoustic pressure at
      the focus in comparison with fully experimental time reversal using an implanted
      hydrophone. In this paper, this simulation-based targeting has been used
      experimentally as a first step for focusing through an ex vivo human skull at a
      single location. It has enabled the creation of a cavitation bubble at focus that
      spontaneously emitted an ultrasonic wave received by the array. This active
      source signal has allowed 97 +/- 1.1% of the reference pressure (hydrophone
      based) to be restored at the geometrical focus. To target points around the focus
      with an optimal pressure level, conventional electronic steering from the initial
      focus has been combined with bubble generation. Thanks to step-by-step bubble
      generation, the electronic steering capabilities of the array through the skull
      were improved.

PMID- 19770085
TI  - Automated analysis of intratidal dynamics of alveolar geometry from microscopic
      endoscopy.
AB  - Alveolar parenchyma, the gas exchange area of the respiratory system, is prone to
      mechanical damage during mechanical ventilation. Development of lung protective
      ventilation strategies therefore requires a better understanding of alveolar
      dynamics during mechanical ventilation. In this paper, we propose a novel method
      for automated analysis of the intratidal geometry of subpleural alveoli based on
      the evaluation of video frames recorded from alveolar microscopy in an
      experimental setting. Our method includes the recording with a microscopic
      endoscope, feature extraction from image data, the analysis of a single frame,
      the tracking and analysis of single alveoli in a video sequence, and the
      evaluation of the obtained sequence of alveolar geometry data. Our method enables
      automated analysis of 2-D alveolar geometry with sufficient temporal resolution
      to follow intratidal dynamics. The developed method and the reproducibility of
      the results were successfully validated with manually segmented video frames.

PMID- 19770086
TI  - Parameter-optimized model of cardiovascular-rotary blood pump interactions.
AB  - A lumped parameter model of human cardiovascular-implantable rotary blood pump
      (iRBP) interaction has been developed based on experimental data recorded in two
      healthy pigs with the iRBP in situ. The model includes descriptions of the left
      and right heart, direct ventricular interaction through the septum and
      pericardium, the systemic and pulmonary circulations, as well as the iRBP. A
      subset of parameters was optimized in a least squares sense to faithfully
      reproduce the experimental measurements (pressures, flows and pump variables).
      Our fitted model compares favorably with our experimental measurements at a range
      of pump operating points. Furthermore, we have also suggested the importance of
      various model features, such as the curvilinearity of the end systolic pressure
      volume relationship, the Starling resistance, the suction resistance, the effect
      of respiration, as well as the influence of the pump inflow and outflow cannulae.
      Alterations of model parameters were done to investigate the circulatory response
      to rotary blood pump assistance under heart failure conditions. The present model
      provides a valuable tool for experiment designs, as well as a platform to aid in
      the development and evaluation of robust physiological pump control algorithms.

PMID- 19770087
TI  - Properties of the stimulus router system, a novel neural prosthesis.
AB  - Various types of neural prostheses (NPs) have been developed to restore motor
      function after neural injury. Surface NPs are noninvasive and inexpensive, but
      are often poorly selective, activating nontargeted muscles and cutaneous sensory
      nerves that can cause discomfort or pain. Implantable NPs are highly selective,
      but invasive and costly. The stimulus router system (SRS) is a novel NP
      consisting of fully implanted leads that "capture" and route some of the current
      flowing between a pair of surface electrodes to the vicinity of a target nerve.
      An SRS lead consists of a "pick-up" terminal that is implanted subcutaneously
      under one of the surface electrodes and a "delivery" terminal that is secured on
      or near the target nerve. We have published a preliminary report on the basic
      properties of the SRS [L. S. Gan , "A new means of transcutaneous coupling for
      neural prostheses," IEEE Trans. Biomed. Eng., vol. 54, no. 3, pp. 509-517, Mar.
      2007]. Here, we further characterize the SRS and identify aspects that maximize
      its performance as a motor NP. The surface current needed to activate nerves with
      an SRS, was found to depend on the proximity of the delivery terminal(s) to the
      nerve, electrode configurations, contact areas of the surface electrodes and
      implanted terminals, and the distance between the surface anode and the delivery
      terminal.

PMID- 19770088
TI  - The myocardial electrical blockade induced by photosensitization reaction.
AB  - The authors studied the application of photosensitization-reaction-induced
      cytotoxicity to establish electrical blockade of myocardial tissue. This
      photosensitization-reaction-induced cytotoxicity, i.e., photodynamic therapy
      (PDT) was performed with chlorine photosensitizer, talaporfin sodium, and a red
      (670 nm) diode laser. The cytotoxicity on rat cardiac myocytes and the electrical
      blockade by PDT using rat myocardial tissue were confirmed. The mechanism of PDT
      induced electrical blockade was investigated. The photosensitization-reaction
      induced cytotoxicity in normal rat cardiac myocytes was obtained in cell
      lethality measurement. The ex vivo experiment with rat-isolated myocardial tissue
      demonstrated the immediate electrical blockade by PDT. Moreover, the possibility
      of permanent electrical blockade by PDT using rat atrioventricular blockade model
      was confirmed. To study the mechanism of the acute electrical blockade obtained
      in the ex vivo study, intracellular Ca2+ concentration changes in rat cardiac
      myocytes were measured by the intensity of the fluorescent Ca2+ indicator Fluo-4
      AM. A rapid increase in fluorescence intensity during the photosensitization
      reaction and a change in cell morphology after the photosensitization reaction
      were observed. These results indicate that cell membrane damage, Ca2+ influx, and
      eventually cell death are caused by the photosensitization reaction. The necrosis
      like cell death induced by the photosensitization reaction can explain a
      permanent electrical blockade of the myocardial tissue in vivo by PDT.

PMID- 19770089
TI  - Reusable ultrasonic tissue mimicking hydrogels containing nonionic surface-active
      agents for visualizing thermal lesions.
AB  - The present study aims to identify a new recipe for reusable tissue mimicking
      phantoms that allows the optical visualization of thermal lesions produced in
      various applications of therapeutic ultrasound where thermal mechanisms are
      important. The phantom was made of polyacrylamide hydrogel containing a nonionic
      surface-active agent (NiSAA) as a temperature-sensitive indicator. Threshold
      temperature above which a thermal lesion is regarded to be formed in the phantom
      is controlled by selecting an NiSAA. In the present study, three NiSAAs of
      polyoxyethylene alkyl ether series with nominal clouding points of 66 ( degrees
      )C, 70 ( degrees )C, and 80 ( degrees ) C were chosen. Test phantoms were
      prepared with polyacrylamide hydrogel, corn syrup and NiSAAs [5% (w/v)]. Key
      acoustic properties of the three NiSAA hydrogels were found to be similar to
      those of human liver. The phantoms were optically transparent at room temperature
      (25 ( degrees ) C) and became opaque after exceeding the clouding points. The
      transparency was recovered on cooling, although the system demonstrated
      hysteresis. The phantoms were tested both in their ability to provide
      visualization of thermal lesions produced by high-intensity focused ultrasound
      and also to examine any characteristic differences in the shape of the lesions
      formed at different threshold temperatures. The present study suggests that the
      NiSAA polyacrylamide hydrogel will be of a practical use in quality assurance in
      various applications of therapeutic ultrasound where thermal mechanisms are
      important.

PMID- 19770090
TI  - Learning Gaussian mixture models with entropy-based criteria.
AB  - In this paper, we address the problem of estimating the parameters of Gaussian
      mixture models. Although the expectation-maximization (EM) algorithm yields the
      maximum-likelihood (ML) solution, its sensitivity to the selection of the
      starting parameters is well-known and it may converge to the boundary of the
      parameter space. Furthermore, the resulting mixture depends on the number of
      selected components, but the optimal number of kernels may be unknown beforehand.
      We introduce the use of the entropy of the probability density function (pdf)
      associated to each kernel to measure the quality of a given mixture model with a
      fixed number of kernels. We propose two methods to approximate the entropy of
      each kernel and a modification of the classical EM algorithm in order to find the
      optimum number of components of the mixture. Moreover, we use two stopping
      criteria: a novel global mixture entropy-based criterion called Gaussianity
      deficiency (GD) and a minimum description length (MDL) principle-based one. Our
      algorithm, called entropy-based EM (EBEM), starts with a unique kernel and
      performs only splitting by selecting the worst kernel attending to GD. We have
      successfully tested it in probability density estimation, pattern classification,
      and color image segmentation. Experimental results improve the ones of other
      state-of-the-art model order selection methods.

PMID- 19770091
TI  - R-POPTVR: a novel reinforcement-based POPTVR fuzzy neural network for pattern
      classification.
AB  - In general, a fuzzy neural network (FNN) is characterized by its learning
      algorithm and its linguistic knowledge representation. However, it does not
      necessarily interact with its environment when the training data is assumed to be
      an accurate description of the environment under consideration. In interactive
      problems, it would be more appropriate for an agent to learn from its own
      experience through interactions with the environment, i.e., reinforcement
      learning. In this paper, three clustering algorithms are developed based on the
      reinforcement learning paradigm. This allows a more accurate description of the
      clusters as the clustering process is influenced by the reinforcement signal.
      They are the REINFORCE clustering technique I (RCT-I), the REINFORCE clustering
      technique II (RCT-II), and the episodic REINFORCE clustering technique (ERCT).
      The integrations of the RCT-I, the RCT-II, and the ERCT within the pseudo-outer
      product truth value restriction (POPTVR), which is a fuzzy neural network
      integrated with the truth restriction value (TVR) inference scheme in its five
      layered feedforward neural network, form the RPOPTVR-I, the RPOPTVR-II, and the
      ERPOPTVR, respectively. The Iris, Phoneme, and Spiral data sets are used for
      benchmarking. For both Iris and Phoneme data, the RPOPTVR is able to yield better
      classification results which are higher than the original POPTVR and the modified
      POPTVR over the three test trials. For the Spiral data set, the RPOPTVR-II is
      able to outperform the others by at least a margin of 5.8% over multiple test
      trials. The three reinforcement-based clustering techniques applied to the POPTVR
      network are able to exhibit the trial-and-error search characteristic that yields
      higher qualitative performance.

PMID- 19770092
TI  - Variational Bayesian mixture model on a subspace of exponential family
      distributions.
AB  - Exponential principal component analysis (e-PCA) has been proposed to reduce the
      dimension of the parameters of probability distributions using Kullback
      information as a distance between two distributions. It also provides a framework
      for dealing with various data types such as binary and integer for which the
      Gaussian assumption on the data distribution is inappropriate. In this paper, we
      introduce a latent variable model for the e-PCA. Assuming the discrete
      distribution on the latent variable leads to mixture models with constraint on
      their parameters. This provides a framework for clustering on the lower
      dimensional subspace of exponential family distributions. We derive a learning
      algorithm for those mixture models based on the variational Bayes (VB) method.
      Although intractable integration is required to implement the algorithm for a
      subspace, an approximation technique using Laplace's method allows us to carry
      out clustering on an arbitrary subspace. Combined with the estimation of the
      subspace, the resulting algorithm performs simultaneous dimensionality reduction
      and clustering. Numerical experiments on synthetic and real data demonstrate its
      effectiveness for extracting the structures of data as a visualization technique
      and its high generalization ability as a density estimation model.

PMID- 19770093
TI  - Pattern classification with class probability output network.
AB  - The output of a classifier is usually determined by the value of a discriminant
      function and a decision is made based on this output which does not necessarily
      represent the posterior probability for the soft decision of classification. In
      this context, it is desirable that the output of a classifier be calibrated in
      such a way to give the meaning of the posterior probability of class membership.
      This paper presents a new method of postprocessing for the probabilistic scaling
      of classifier's output. For this purpose, the output of a classifier is analyzed
      and the distribution of the output is described by the beta distribution
      parameters. For more accurate approximation of class output distribution, the
      beta distribution parameters as well as the kernel parameters describing the
      discriminant function are adjusted in such a way to improve the uniformity of
      beta cumulative distribution function (CDF) values for the given class output
      samples. As a result, the classifier with the proposed scaling method referred to
      as the class probability output network (CPON) can provide accurate posterior
      probabilities for the soft decision of classification. To show the effectiveness
      of the proposed method, the simulation for pattern classification using the
      support vector machine (SVM) classifiers is performed for the University of
      California at Irvine (UCI) data sets. The simulation results using the SVM
      classifiers with the proposed CPON demonstrated a statistically meaningful
      performance improvement over the SVM and SVM-related classifiers, and also other
      probabilistic scaling methods.

PMID- 19770094
TI  - Bilateral renal and jejunal metastasis of choriocarcinoma presenting as
      spontaneous renal hemorrhage.
AB  - Spontaneous renal hemorrhage (SRH) is a difficult diagnostic problem with various
      causes. We report a case of SRH and episodic gross hematuria in a patient with
      metastatic choriocarcinoma involving both kidneys for which successful
      angioembolization was carried out for control of hemorrhage. There was no
      evidence of primary uterine tumor and pulmonary or liver involvement. The patient
      developed gastrointestinal bleeding due to jejunal metastasis while on
      chemotherapy and surgical resection of the involved segment was carried. However,
      the patient acquired nosocomial pneumonia and succumbed to sepsis in the
      postoperative period.

PMID- 19770095
TI  - [Influenza A(H1N1) epidemic in Argentina. Experience in a National General
      Hospital (Hospital Nacional Alejandro Posadas)].
AB  - The preparation and medical care during the influenza A(H1N1) outbreak (June
      2009) in a high complexity level, public, general hospital with laboratory
      diagnosis, general and intensive care (ICU) hospitalization is described. A plan
      was designed to increase the hospital's surge capacity, reallocate resources and
      guarantee bio-safety. The number of consultations was 7.1 +/- 3.8 times higher
      than during June 2006-2008. Detection of A(H1N1) cases were confirmed by PCR-RT
      in 186/486 (38.3%) in-patients and 56/176 (31.8%) out-patients. Median age among
      in-patients was 20 years; 75% <45 and 32.3% <15. Global mortality: 6.8%; 9.1%
      among confirmed cases. Adults were directed to a reception area of out-patient
      care, hospitalization (isolation) and mechanical ventilation. general ward: 110
      patients with oxygen saturation <96% and/or risk factors (65.5% had asthma,
      chronic obstructive pulmonary disease, obesity, pregnancy or other) were admitted
      (5 times more than in 1999-2006). Chest X-ray showed lung infiltrates and/or lung
      consolidation in 97.3%. Severe hypoxemia: 43.5%. There were no significant
      clinical or X-ray differences between 21/49 confirmed and non confirmed A(H1N1)
      cases. TREATMENT: oseltamivir, ampicillin-sulbactam, and clarithromycin. ICU: 28
      severe pneumonia patients were admitted (21 with associated conditions); 24 with
      acute respiratory distress syndrome received mechanical ventilation, 21 of them
      had shock; 8/9 acute renal failure cases required hemodialysis. Mortality: 14/28;
      7/14 with confirmed A(H1N1) infection. Seventy A(H1N1) infected children were
      hospitalized (27 required ICU, 6 of them died). The children's median age was 11
      months; 61.8% presented comorbidities (prematurity, asthma, broncho-pulmonary
      dysplasia and congenital heart disease). Oseltamivir and antibiotics were
      administered. Children's mortality: 8.6%

PMID- 19770096
TI  - [Vectorial and congenital transmission of Trypanosoma cruzi in Las Lomitas,
      Formosa].
AB  - Chagas disease, caused by Trypanosoma cruzi, is a major cause of morbidity and
      mortality in Latin America. The objective of this study was to describe the rate
      of infestation in four aboriginal communities in Las Lomitas (Great Chaco
      Region), Formosa, Argentina; the rate of infection in children residing in these
      communities, in blood donors and in pregnant women who received care at the
      Hospital Las Lomitas, as well as the rate of congenital infection in children
      born to women infected during the study period. The rate of infestation of 172
      households evaluated in 2006 reached 32%. Prevalence of infection among 445
      people was 17.5% and in children under 5 years old it was 8.6%. The rate of
      infection reached 18.6% in blood donors and 29.1% in pregnant women. The rate of
      infection among 47 children born to infected women, and living in residences
      under vectorial surveillance was 17.0%. These infections were considered as
      congenital. This study showed indexes compatible with active vectorial
      transmission at the beginning. After vectorial control with insecticides the
      infestation rate has been reduced to 3.3%. The local health system has introduced
      high impact procedures of primary and secondary prevention in order to prevent
      new cases and to treat infected people.

PMID- 19770097
TI  - Adult height in Turner Syndrome girls after long-term growth hormone treatment.
AB  - We studied the adult height (AH) outcome, and factors likely to influence it, in
      Turner Syndrome (TS) girls treated with growth hormone (GH). A total of 25 TS
      girls treated with GH were compared with 10 TS girls not treated with GH. The
      percentage of girls who achieved normal third percentile was determined.
      Projected AH (PAH) was calculated according to height standard deviation score
      (HSDS) at the beginning of the treatment. Gain in height was determined as: AH -
      pretreatment PAH. The percentage of girls who achieved target range (midparental
      height +/- 2 SD) was determined. Multiple linear regression models were fitted on
      baseline variables- chronological age (CA), midparental height (MPH) and HSDS;
      and treatment variables- duration of oestrogen-free GH therapy and duration of GH
      therapy+oestrogens. As for baseline data: Median CA was 13.0 years (5.6-15.8).
      Mean HSDS was 0.25 +/- 1.1 SDS. PAH was 139.2 +/- 5.6 cm. MPH was 160.0 +/- 5.0
      cm. As for follow up data: Median CA at onset oestrogens was 15.1 years (13.2
      16.6). Median duration of GH therapy was 3.8 years (2.1-10.3). Median oestrogen
      free GH period was 2.0 years (0.7-7.8), and median GH+oestrogens period, 1.8
      years (1.0-3.2). Adult height: Mean AH was 150.4 +/- 7.0 cm in treated patients
      and 140.8 +/- 7.2 cm in the group not treated with GH (p=0.001). Fourteen (56%)
      girls achieved normal third percentile compared with an initially predicted 1
      (4%). Gain in height was 11.2 +/- 3.7 cm. Thirteen (59%) girls reached an AH
      within target range. HSDS at the beginning of the treatment was the variable most
      strongly related to AH and duration of oestrogen-free GH period was the variable
      most strongly related to gain in height.

PMID- 19770098
TI  - [P-glycoprotein functional activity in peripheral blood lymphocytes in ulcerative
      colitis].
AB  - P-glycoprotein (P-gp), encoded by MDR-1, is a transmembrane efflux pump that has
      been involved in relevant clinical drug transport. It is expressed in
      lymphocytes, luminal epithelium of colon and other tissues with barrier function.
      MDR1 was proposed as a candidate gene for ulcerative colitis. The aim of the
      present work was to investigate the role of P-gp in therapeutic response of
      ulcerative colitis by studying its functionality in lymphocytes isolated from
      peripheral blood. Samples were taken from 27 patients with active colitis
      classified clinically in refractory (n = 16) and responders (n = 11) to
      treatment. Rhodamine 123 (a fluorescent P-glycoprotein substrate) efflux was
      studied by flow cytometry as absence and presence of an inhibitor (verapamil, 100
      uM). Data were expressed evaluating the behaviour of two markers defined based on
      % of cells with maximum (M1)/minimum (M2) intracellular fluorescence, reflecting
      inactivity/activity of the pump. Results were compared with a group of healthy
      individuals (n = 68). Significant differences were observed in absence and
      presence of Verapamil inhibition, when comparing refractory vs. responders (p <
      0.05) as well as refractory vs. healthy controls (p < 0.01). No differences were
      observed when comparing responders vs. controls (p > 0.05) (Kruskal-Wallis test
      and Dunn post-test). Rhodamine efflux assay was also performed in 12 patients who
      required therapeutic change; a significant diminish of rhodamine transport (p <
      0.01) was observed without inhibitor when patients achieved clinical response.
      Finally, our results suggest a possible relevant role of P-gp in ulcerative
      colitis treatment response and a possible usefulness of P-gp functional assay in
      the early detection of individual therapeutic response.

PMID- 19770099
TI  - [Neutrophils without CD16b receptors].
AB  - Occurrence of the rare CD16b deficiency ("null" phenotype) in neutrophils from
      two female patients (41 and 15 years old) is reported. The first case was
      referred with a diagnosis of anemia related to paroxistic nocturnal
      hemoglobinuria and the second case, with presumptive diagnosis of immune
      neutropenia. In both cases, absence of CD16b expression was determined by flow
      cytometry without deficiencies of other neutrophil alloantigens or defects of
      membrane anchorage through glycosil phosphatydil inositol (GPI) linkage. Clinical
      manifestations in both patients could not be attributed exclusively to the
      absence of CD16b, as other receptors for the IgG Fc fragment (CD32 and CD64)
      could compensate this deficiency that occurs in <1% of the caucasic population.
      Nevertheless, it is important to take this rare deficiency into account in order
      to prevent isoantibody formation after eventual blood transfusions, or transient
      neonatal immune neutropenia in children born to women with the "null" phenotype.

PMID- 19770100
TI  - [Exenatide trials for the treatment of type 2 diabetes].
AB  - Type 2 diabetes mellitus is a common, chronic and progressive metabolic disorder,
      which accounts for 90% of diabetes cases worldwide. Approximately 60% of
      individuals with the disease do not achieve target glycosylated hemoglobin
      levels, despite the availability of many antidiabetic agents. The two most
      important needs in the present management of diabetes are the ability of
      antidiabetic agents to exhibit prolonged efficacy in reducing hyperglycemia and
      to preserve beta-cell function. The incretin effect appears to be reduced in
      patients with type 2 diabetes. Exenatide is the first in a novel class of
      antidiabetic drugs that improves glycemic control in patients with type 2
      diabetes through several physiological glucoregulatory mechanisms which improve
      the incretin effect. Overall, mean glycosylated hemoglobin (HbA1c) reductions
      achieved in the exenatide phase III clinical trials were in the order of 1%. Long
      term data from the uncontrolled open-label extension studies indicate that
      adjunctive exenatide therapy leads to sustained improvements in HbA1c and
      progressive weight loss for at least 3 years. The drug is generally well
      tolerated. The most common adverse events were gastrointestinal in nature and
      mild to moderate in severity. The objective of this review is to discuss the
      available published evidence on exenatide therapeutic efficacy and tolerability,
      and the role of this new drug in the treatment of type 2 diabetes.

PMID- 19770101
TI  - [Carotidynia ].

PMID- 19770103
TI  - [Tolerance and autoimmunity. Novel therapeutic approaches].
AB  - The main function of the immune system is to protect the individual against
      potentially dangerous pathogens. It comprises innate and adaptive cellular and
      soluble components, both with the capacity to discriminate between harmful and
      harmless. These processes are regulated by homeostatic mechanisms that constitute
      the so-called immunological tolerance, which aims to limit the prolonged action
      of immune mediators and to silence the generation of potentially autoaggressive
      components. Failure to silence self-reactive T and B cells results in the
      generation of autoimmune disease. Recent advances in our knowledge of these
      pathological entities have opened a new chapter in the pharmacology of the immune
      system. Its promising potential currently offers new therapeutic agents to
      control and attenuate pathological tissue damage. Nevertheless, further research
      regarding these biologic agents is required, since they are not free from
      inconveniences. It is without question that upcoming findings in this field will
      instill hope into the quest for the "magic bullet".

PMID- 19770102
TI  - [Klippel-Feil syndrome].

PMID- 19770104
TI  - [Cerebral proteolysis of amiloid-b peptide: relevance of insulin-degrading enzyme
      in Alzheimer's disease].
AB  - The global increase in life expectancy turns Alzheimer's disease (AD) into a
      growing problem. One of the distinctive features of AD is the excessive
      accumulation of amyloid-b (Ab) peptide in the brain. In recent years, a concept
      that has gained strength is that degradation of Ab by proteases in situ is an
      important mechanism that prevents cerebral peptide accumulation. Biochemical and
      genetic data have shown that insulin-degrading enzyme (IDE) participates in Ab
      and insulin homeostasis. IDE expression and activity are significantly decreased
      in AD brains compared to age-matched controls. Also, IDE is deposited with Ab in
      senile plaques and blood vessels, indicating a gross conformational change as a
      consequence of diverse post-translational mechanisms. These alterations in IDE
      distribution and activity may result in insufficient degradation of Ab and
      insulin, promoting the formation of Ab oligomers and hormone resistance. Both
      processes might play a fundamental part in neurodegeneration. The study of the
      clearance mechanisms of cerebral Ab will not only aid in the understanding AD
      pathogenesis but will also allow a better interpretation of ongoing clinical
      trials and the development of new therapeutic strategies.

PMID- 19770105
TI  - [Arrival and dissemination of a pandemic influenza virus. Role of the national
      reference laboratory.].

PMID- 19770106
TI  - [Initial characteristics of the novel A(H1N1) pandemic in Argentina].

PMID- 19770107
TI  - [Lazzaro Spallanzani and artificial insemination].

PMID- 19770108
TI  - [Human food. A biological and medical perspective].

PMID- 19770109
TI  - [In the care of specialists].

PMID- 19770110
TI  - [The inland flu].

PMID- 19770111
TI  - [Alfred russel wallace and civilization].

PMID- 19770112
TI  - Municipal governments' role in averting access problems associated with market
      reform.
AB  - BACKGROUND: The 2006 health insurance legislation obligates each resident to
      purchase a basic health policy. If a person fails to purchase a basic health
      plan, (s)he is by implication uninsured. An assumption underpinning the new
      legislation is that consumers must take responsibility for themselves and can
      make informed choices. In the view of municipal governments, social security
      recipients in their community often are not competent enough to do so and for
      that reason need support. The study investigates how municipal governments
      provided them with administrative support to prevent them becoming uninsured.
      METHODS: Empirical data for this research were collected by desk research.
      RESULTS: Municipal governments actively support social security recipients.
      Individual responsibility and consumer choice are good for the great majority of
      the population, but may entail problems for social security recipients. To avoid
      that they are uninsured or become a defaulter, municipal governments conclude a
      group contract with health insurers. There are clear indications that this
      strategy has been effective to reduce the number of uninsured people. CONCLUSION:
      Health insurance legislation based on the principle of individual responsibility
      requires a policy to support social security recipients in society. Such a policy
      may imply restrictions to individual responsibility.

PMID- 19770114
TI  - Three-dimensional echocardiographic assessments of exercise-induced changes in
      left ventricular shape and dyssynchrony in patients with dynamic functional
      mitral regurgitation.
AB  - AIMS: Left ventricular (LV) shape and LV dyssynchrony are two cofactors
      associated with functional mitral regurgitation (MR) in patients with heart
      failure. Both can be accurately examined by real-time three-dimensional
      echocardiography (3DE). We examined the relationship between dynamic MR and
      exercise-induced changes in LV shape and synchronicity using 3DE. METHODS AND
      RESULTS: Fifty patients with systolic LV dysfunction underwent 2D and 3D
      quantitative assessment of LV function, shape, and synchronicity at rest and
      during symptom-limited exercise test. According to the magnitude of change in MR,
      patients were divided into EMR group (15 patients, 30%), if the degree of MR
      increased during test, and NEMR group. During exercise, the changes in LV volumes
      and ejection fraction were similar in both groups, whereas changes in mitral
      valvular deformation parameters, in LV sphericity index, and in the extent of LV
      dyssynchrony were more pronounced in the EMR group. At rest, only the 3D
      sphericity index could distinguish the two groups. By stepwise multiple
      regression model, dynamic changes in the systolic dyssynchrony index, sphericity
      index, and coaptation distance were associated with dynamic MR (r(2) = 0.45, P =
      0.012). CONCLUSION: Dynamic MR during exercise is related to the 3D changes in LV
      shape and in LV synchronicity.

PMID- 19770115
TI  - The theory and practice of markets in health care.

PMID- 19770116
TI  - Evidence-based design of health care facilities.

PMID- 19770117
TI  - What medical specialists like and dislike about health technology assessment
      reports.
AB  - OBJECTIVE: To examine how medical specialists view health technology assessment
      (HTA) and its role in policy-making. METHODS: Semi-structured interviews with 28
      medical specialists practising in Quebec and Ontario (Canada) to examine their
      views on an HTA report relevant to their specialty (prostate-specific antigen
      screening, electroconvulsive therapy and prenatal screening for Down's syndrome).
      RESULTS: Medical specialists represent a particularly demanding audience for HTA
      producers because they are knowledgeable about current studies in their field and
      often contribute to the evidence base that HTA seeks to synthesize. In all three
      cases, specialists not only challenged specific points in the content of the HTA
      reports but also offered different and sometimes conflicting appraisals of the
      clinical relevance and policy implications. More than just the timeliness and
      usefulness of HTA findings are at issue. The views of specialists are grounded in
      a clinical understanding of what counts as evidence and how decisions should be
      made, a view that contrasts with the societal perspective of HTA. CONCLUSIONS:
      HTA producers cannot afford to overlook medical specialists who play a key role
      in the adoption of health technologies. Establishing a transparent dialogue
      between producers and users of HTA reports could enrich policy recommendations.

PMID- 19770118
TI  - Bringing genetics into primary care: findings from a national evaluation of
      pilots in England.
AB  - OBJECTIVES: Developments in genetic knowledge and clinical applications are seen
      as rendering traditional modes of organizing genetics provision increasingly
      inappropriate. In common with a number of developed world countries the UK has
      sought to increase the role of primary care in delivering such services. However,
      efforts to reconfigure service delivery face multiple challenges associated with
      divergent policy objectives, organizational boundaries and professional cultures.
      This paper presents findings from an evaluation of an English initiative to
      integrate genetics into 'mainstream' clinical provision in the National Health
      Service. METHODS: Qualitative research in 11 case-study sites focusing on
      attempts by pilots funded by the initiative to embed knowledge and provision
      within primary care illustrating barriers faced and the ways in which these were
      surmounted. RESULTS: Lack of intrinsic interest in clinical genetics among
      primary care staff was compounded by national targets that focused their
      attention elsewhere and by service structures that rendered genetics a peripheral
      concern demanding minimal engagement. Established divisions between the
      commissioning of mainstream and specialist services, along with the pressures of
      shorter-term targets, impeded ongoing funding. CONCLUSIONS: More wide-ranging
      policy and organizational support is required if the aim of entrenching genetics
      knowledge and practice across the Health Service is to be realized.

PMID- 19770119
TI  - Evidence-based practice in British complementary and alternative medicine: double
      standards?
AB  - OBJECTIVES: The principles of evidence-based practice (EBP) are fundamental to
      medical ethics and seem essential for any form of health care. In 2000, a House
      of Lords Select Committee recommended that the ethos of EBP should extend to
      complementary and alternative medicine. The aim of this investigation was to
      determine whether EBP is incorporated in the codes of ethics of British
      complementary and alternative medicine organizations. METHODS: We obtained the
      codes of the following bodies: Association of Naturopathic Practitioners,
      Association of Traditional Chinese Medicine (UK), Ayurvedic Practitioners
      Association, British Acupuncture Council, Complementary and Natural Healthcare
      Council, European Herbal Practitioners Association, General Chiropractic Council,
      General Osteopathic Council, General Regulatory Council for Complementary
      Therapies, National Institute of Medical Herbalists, Register of Chinese Herbal
      Medicine, Society of Homeopaths, UK Healers, Unified Register of Herbal
      Practitioners. We then extracted the statements referring to EBP and compared
      this with what the respective codes of British doctors and nurses proscribed.
      RESULTS: Only the General Chiropractic Council, the General Osteopathic Council
      and the General Regulatory Council for Complementary Therapies oblige their
      members to adopt EBP. CONCLUSIONS: This discloses double standards in UK health
      care which may compromise patient safety.

PMID- 19770120
TI  - Commentary: motes, beams and evidence-based practice.

PMID- 19770122
TI  - Evaluation of the impact of program budgeting and marginal analysis in Vancouver
      Island Health Authority.
AB  - OBJECTIVE: The objective of this research was to provide further insights into
      the ability of Program Budgeting and Marginal Analysis (PBMA) to help health care
      decision-makers in deciding where to allocate scarce resources so as to best meet
      their organizational objectives. METHODS: We report on a case study of PBMA
      implementation. The main source of information was two sets of semi-structured
      evaluation interviews conducted with senior decision-makers after each of the
      first two years of PBMA implementation in Vancouver Island Health Authority
      (VIHA), Canada. These interviews were analysed thematically, with initial coding
      based upon themes that had been identified in the previous stage of the research.
      RESULTS: Many of the initial problems with PBMA implementation resolved
      themselves over time as participants became more familiar with the process.
      However, some problems needed to be addressed explicitly through changes in
      procedures. Establishing procedures for handling 'must-dos' (i.e. spending
      priorities, that are externally mandated) did not replace the need to define
      explicitly the extent of the organization's discretionary spending authority.
      CONCLUSION: Faced with claims that typically outstrip available resources, health
      care decision-makers need a process to guide allocation decisions. PBMA has
      demonstrated at VIHA an ability to handle some of the key issues associated with
      this challenge. Our analysis has produced lessons that should facilitate future
      implementation but has also shown that resource allocation criteria selection and
      the extent of executive discretion are likely to be ongoing challenges.

PMID- 19770121
TI  - A Bayesian method for the synthesis of evidence from qualitative and quantitative
      reports: the example of antiretroviral medication adherence.
AB  - OBJECTIVES: Bayesian meta-analysis is a frequently cited but very little-used
      method for synthesizing qualitative and quantitative research findings. The only
      example published to date used qualitative data to generate an informative prior
      probability and quantitative data to generate the likelihood. We developed a
      method to incorporate both qualitative and quantitative evidence in the
      likelihood in a Bayesian synthesis of evidence about the relationship between
      regimen complexity and medication adherence. METHODS: Data were from 11
      qualitative and six quantitative studies. We updated two different non
      informative prior distributions with qualitative and quantitative findings to
      find the posterior distribution for the probabilities that a more complex regimen
      was associated with lower adherence and that a less complex regimen was
      associated with greater adherence. RESULTS: The posterior mode for the
      qualitative findings regarding more complex regimen and lesser adherence (using
      the uniform prior with Jeffreys' prior yielding highly similar estimates) was
      0.588 (95% credible set limits 0.519, 0.663) and for the quantitative findings
      was 0.224 (0.203, 0.245); due to non-overlapping credible sets, we did not
      combine them. The posterior mode for the qualitative findings regarding less
      complex regimen and greater adherence was 0.288 (0.214, 0.441) and for the
      quantitative findings was 0.272 (0.118, 0.437); the combined estimate was 0.299
      (0.267, 0.334). CONCLUSIONS: The utility of Bayesian methods for synthesizing
      qualitative and quantitative research findings at the participant level may
      depend on the nature of the relationship being synthesized and on how well the
      findings are represented in the individual reports.

PMID- 19770123
TI  - Equity in the distribution of community pharmacies in England: impact of
      regulatory reform.
AB  - OBJECTIVES: To examine whether relaxation of control of entry regulations for
      community pharmacy contracts in England, introduced in 2005, affected the
      distribution of community pharmacies relative to population need indicators.
      METHODS: Community pharmacy locations and population need indicators were used to
      calculate three summary measures of distributional equity across Primary Care
      Trust (PCT) areas (n = 152): the Gini coefficient, Atkinson Index and community
      pharmacies per PCT population. The indicators were adjusted for need using data
      from NHS GP contract Quality and Outcomes Framework disease registers,
      deprivation, all-cause mortality and elderly population rates. RESULTS: Numbers
      of community pharmacies increased by 397 (4%) between 2005 and 2007 with three
      supermarket chains accounting for 152 (38%) of new pharmacies. Over one-quarter
      of PCTs experienced increases of 5% or more in community pharmacies per capita
      between 2005 and 2007. Gini and Atkinson indicators showed small increases in
      distributional equity across all population needs indicators. CONCLUSION:
      Deregulation was associated with more community pharmacies per capita and a small
      increase in geographic equity of community pharmacy distribution at PCT level.
      Future research should continue to monitor how pharmacy distribution changes over
      time and assess the extent to which the new regulatory framework has allowed
      clustering of pharmacies which could result in increased inequity below PCT
      level.

PMID- 19770124
TI  - Assessment and accountability.

PMID- 19770125
TI  - Images in health care: potential and problems.
AB  - Although communication issues within health care have received greater research
      and policy attention in recent years, one growing aspect of such communication
      has been largely overlooked. In this paper we suggest that visual forms of
      communication, at both the individual and population level, are increasingly used
      and relied upon. This seems appropriate given a general shift towards a more
      visual and visually literate society, and the potential of images to convey
      complex information and influence both beliefs and emotion. However, we also
      argue that the widespread use of such a potentially powerful tool necessitates a
      solid evidence base that is currently lacking. Such a lack leaves image-based
      interventions at best potentially ineffective and at worst harmful. We examine
      the reasons for the paucity of research in this area and suggest that in fact a
      multitude of supportive research and theory exists but that at present it is
      spread across a range of academic fields with little interdisciplinary dialogue.
      Given the current desire to see increased inter- and multidisciplinary dialogue
      and the acceptance of the need for theoretical and empirical underpinnings for
      complex interventions, it would seem that there may now be both the will and the
      way forward to forge new collaborations, integrate such theories and develop a
      more sophisticated evidence base to support the growing use of images in health
      care settings.

PMID- 19770126
TI  - In vitro post-meiotic germ cell development from human embryonic stem cells.
AB  - BACKGROUND: Investigating the mechanisms of human primordial germ cell (PGC) and
      gamete development are important for understanding the causes of infertility and
      effects of environmental chemicals on reproductive development. However, there
      are practical and ethical difficulties associated with obtaining human tissue in
      early development. The aim of this study was to investigate whether human
      embryonic stem cell-hESC-generated germ cells could provide an in vitro model of
      gamete development. METHOD: Human ESCs were differentiated as embryoid bodies
      (EBs) in vitro. Gene and protein marker expression profiles of EBs in different
      periods of culture were analysed by quantitative polymerase chain reaction (Q
      PCR) and immunolocalization to monitor germ cell development. Secretion of
      hormones involved in germ cell maturation was measured, to detect the existence
      of a germ cell niche within EBs. RESULTS: Q-PCR revealed gene expression profiles
      consistent with PGC formation and germ cell development. A small population of
      post-meiotic spermatid cells were identified using sperm-specific antibodies
      (Protamine 1 and 1.97). Although gene expression profiles characteristic of
      oocyte development and follicle-like structures were detected, a committed oocyte
      with extra-cellular zona pellucida was not recognized with zona pellucida
      specific monoclonal antibody. CONCLUSIONS: hESCs can form PGCs and post-meiotic
      spermatids in vitro, however, there remains doubt about oocyte development.
      Levels of steroid hormones produced by EBs were significant when compared with
      known values for a similar quantity of human testis, suggesting that hESC may
      intrinsically create a favourable hormonal niche for spermatogenesis.

PMID- 19770127
TI  - Trends and determinants of reproductive health service use among young women in
      the USA.
AB  - BACKGROUND: This study explores the current patterns of reproductive health
      service use among young women in the USA and the changing influence of socio
      demographic factors on the types of services used over time. METHODS: The study
      population, drawn from the two last cycles of the National Survey of Family
      Growth, consists of women aged 15-24 (n = 2543 in 1995, n = 2157 in 2002). We
      examined trends in use of 'contraceptive services' and 'other reproductive health
      services for preventive care' and tested for changes in the patterns of use of
      these services over time. Logistic regression models were used to further clarify
      the factors associated with the use of the two types of services in 2002.
      RESULTS: Results show no difference in the overall use of reproductive health
      services in the past year but did reveal changes in the type of service sought.
      Use of services for contraception increased by 10 percentage points (39.3% in
      1995 to 49.7% in 2002, P < 0.001), although the use of other services remained
      stable (53.2% in 1995, 50.2% in 2002, P = 0.14). The patterns of use varied over
      time, exhibiting growing social disparities. In 2002, the use of contraceptive
      services depended on women's age, number of partners, personal and mother's level
      of education, and menstrual problems. The use of other reproductive health
      services for preventive care varied across women's socio-economic background.
      CONCLUSION: This study demonstrates increasing social differentials in the use of
      reproductive health services for preventive care among young women in the USA
      between 1995 and 2002, a finding which calls for careful monitoring in the
      context of limited resources.

PMID- 19770128
TI  - Structural basis of the affinity for oligomannosides and analogs displayed by
      BC2L-A, a Burkholderia cenocepacia soluble lectin.
AB  - The opportunistic pathogen Burkholderia cenocepacia contains three soluble
      carbohydrate-binding proteins, related to the fucose-binding lectin PA-IIL from
      Pseudomonas aeruginosa. All contain a PA-IIL-like domain and two of them have an
      additional N-terminal domain that displays no sequence similarities with known
      proteins. Printed arrays screening performed on the shortest one, B. cenocepacia
      lectin A (BC2L-A), demonstrated the strict specificity for oligomannose-type N
      glycan structures (Lameignere E, Malinovska L, Slavikova M, Duchaud E, Mitchell
      EP, Varrot A, Sedo O, Imberty A, Wimmerova M. 2008. Structural basis for mannose
      recognition by a lectin from opportunistic bacteria Burkholderia cenocepacia.
      Biochem J. 411:307-318.). The disaccharides alphaMan1-2Man, alphaMan1-3Man, and
      alphaMan1-6Man and the trisaccharide alphaMan1-3(alphaMan1-6)Man were tested by
      titration microcalorimetry in order to evaluate their affinity for BC2L-A in
      solution and to characterize the thermodynamics of the binding. Oligomannose
      analogs presenting two mannoside residues separated by either flexible or rigid
      spacer were also tested. Only the rigid one yields to high affinity binding with
      a fast kinetics of clustering, while the flexible analog and the trimannoside
      display moderate affinities and no clustering effect on short time scale. The
      crystal structures of BC2L-A have been obtained in complex with alphaMan1-3Man
      disaccharide and alphaMan1(alphaMan1-6)-3Man trisaccharide. The lengthy time
      required for the co-crystallization with the trisaccharide allowed for the
      formation of cluster since in the BC2L-A-trimannose complex solved at 1.1 A
      resolution, the sugar creates a bridge between two adjacent dimers, yielding to
      molecular strings. AFM experiments were performed in order to visualize the
      filaments formed in solution by this type of interaction.

PMID- 19770129
TI  - A phase II study of cisplatin and irinotecan as induction chemotherapy followed
      by accelerated hyperfractionated thoracic radiotherapy with daily low-dose
      carboplatin in unresectable stage III non-small cell lung cancer: JCOG 9510.
AB  - OBJECTIVE: It is important to find optimal regimens of cisplatin (CDDP)-based
      third-generation chemotherapy and radiotherapy for patients with unresectable
      Stage III non-small cell lung cancer (NSCLC). METHODS: This Phase II study was
      designed to determine the toxicity and efficacy of two courses of chemotherapy
      (CDDP 80 mg/m(2) on day 1 and irinotecan 60 mg/m(2) on days 1 and 8) followed by
      accelerated hyperfractionated thoracic radiotherapy (60 Gy/40 fractions in 4
      weeks) combined with daily carboplatin (CBDCA) administration. CBDCA was
      administered at a target area under the plasma level-time curve of 0.4 x (24 h
      creatinine clearance + 25), according to Calvert's formula. RESULTS: Twenty-six
      patients were enrolled in the study. The patients' median age was 63 years (range
      40-74 years) and included 22 males and 4 females. Seven patients were Stage IIIA
      and 19 were Stage IIIB. Twenty had a performance status (PS) of 1 versus six with
      a PS of 0. There was one treatment-related death due to sepsis and pneumonia
      associated with Grade 4 neutropenia and diarrhea during chemotherapy. Grade 3 or
      4 neutropenia and diarrhea were observed in 14 and 5 patients, respectively.
      Toxicity of the radiotherapy was mild. There were 0 complete response and 13
      partial responses, giving a response rate of 50.0%. Median survival time and 2
      year survival were 16.4 months and 21.5%, respectively. This study was designed
      with Simon's two-stage design, and the response rate did not meet the criteria to
      proceed to the second stage and the study was terminated early. CONCLUSIONS: This
      regimen might be inactive for patients with unresectable Stage III NSCLC.

PMID- 19770130
TI  - Relationship between tumor-infiltrating T lymphocytes and clinical response after
      reduced-intensity allogeneic hematopoietic stem cell transplantation for advanced
      renal cell carcinoma: a single center prospective study.
AB  - OBJECTIVE: Renal cell carcinoma (RCC) is refractory to conventional therapy,
      including chemotherapy and radiation. However, because RCC is sensitive to
      cytokine therapy, an immunotherapeutic approach such as hematopoietic stem cell
      transplantation (HSCT) might lead to a cure. We performed an institutional
      clinical study of HSCT for refractory RCC patients. METHODS: RCC patients aged 50
      years or over, refractory to therapy, were eligible for the study. HSCT was
      performed after reduced-intensity conditioning. Primary endpoint was defined as
      the survival at day 100 after HSCT with complete donor chimerism, and secondary
      endpoint was the effectiveness of HSCT. RESULTS: Seven patients, provided with
      written informed consent, were enrolled in the study. Six of the seven patients
      achieved complete donor chimera at day 30 after HSCT, but one patient received
      second HSCT because of graft rejection. Four patients achieved a partial response
      (PR) and stable disease was observed in another patient, but these responses were
      temporary. The disease of the other two patients became progressive. Autopsy
      findings revealed an accumulation of CD8(+) lymphocytes and degenerative changes
      in the local RCC lesion in three of six patients who responded clinically. An
      autopsy of a patient who had obtained a PR revealed lymphocyte involvement with a
      cytotoxic T cell (CTL) phenotype in the metastasis of RCC. CONCLUSIONS: Our
      results demonstrate the efficacy of HSCT for RCC and suggest that the graft
      versus-tumor effect elicited by CTLs is induced in vivo. HSCT should be further
      explored as a potential curative treatment for RCC.

PMID- 19770131
TI  - A case of long-term survival after surgical resection of solitary pulmonary
      metastasis from gastric cancer.
AB  - We describe a 60-year-old male patient who survived for a long period after
      pulmonary metastasectomy for gastric cancer. The patient initially underwent
      distal gastrectomy for gastric cancer. Seventeen months after the gastrectomy,
      surgical resection of solitary pulmonary metastasis was performed and following
      resection, the patient has survived without relapse for more than 5 years.
      Carefully selected patients have a good chance of benefiting from pulmonary
      metastasectomy for gastric cancer.

PMID- 19770132
TI  - Phase II trial of gemcitabine combined with 5-fluorouracil and cisplatin (GFP)
      chemotherapy in patients with advanced biliary tree cancers.
AB  - OBJECTIVE: Advanced biliary tree cancers are often diagnosed at an advanced or
      metastatic stage and have poor prognoses. We reported the promising anti-tumor
      activity of gemcitabine/5-fluorouracil (5-FU)/cisplatin (CDDP) therapy, called
      'GFP chemotherapy' in a pilot study. METHODS: Twenty-one patients with advanced
      or metastatic biliary tree cancers with no prior chemotherapy were enrolled in
      this Phase II trial. Patients were treated on 4-week cycle GFP chemotherapy
      consisting of gemcitabine at 1000 mg/m(2) on days 1, 8 and 15, and 5-FU at 150
      mg/m(2) and CDDP at 3 mg/m(2) on days 1-5, 8-12 and 15-19. After two cycles, a 4
      week outpatient treatment of gemcitabine (1000 mg/m(2)) on days 1 and 15 combined
      with 5-FU (500 mg/m(2)) and CDDP (7 mg/m(2)) on days 1 and 15 was commenced.
      Treatment was repeated until tumor progression or remission allowing curative
      operation, or unacceptable toxicity occurred. RESULTS: Of these 21 patients, no
      complete responses were observed, but 7 patients (33.3%) demonstrated partial
      responses (PRs) with an additional 12 patients (57.2%) having stable diseases, as
      assessed by RECIST. Three patients with PRs were treated by curative operation
      after GFP chemotherapy, and all of them survived with no recurrence for over 3
      years. The median overall survival time was 18.8 months, and median time to
      progression was 13.4 months. Grade 3 side effects such as leukopenia,
      thrombocytopenia and anemia were found in six patients (28.6%), but no patients
      dropped out because of toxicity. CONCLUSIONS: This GFP chemotherapy has promising
      anti-tumor activity and is well tolerated in patients with advanced biliary tree
      cancers.

PMID- 19770133
TI  - Concurrent benign schwannoma of oesophagus and posterior mediastinum.
AB  - A 52-year-old female with recent onset dysphagia and haematemesis was found to
      have an intramural tumour of the oesophagus. A separate tumour in the posterior
      mediastinum was also detected. Both the tumours were immunohistochemically and
      histomorphologically compatible with benign schwannoma. Oesophageal schwannoma is
      extremely rare and its association with a concurrent schwannoma in posterior
      mediastinum is not reported earlier in the literature.

PMID- 19770134
TI  - Early outcomes of video-assisted thoracoscopic resection of thymus in 181
      patients with myasthenia gravis: who are the candidates for the next morning
      discharge?
AB  - The aims of this study are to present the results of videothoracoscopic
      thymectomy in patients with myasthenia gravis (MG) and to predict the factors
      affecting the next morning discharge (NMD). This is a retrospective analysis of
      the prospectively recorded data of 181 consecutive myasthenic patients who
      underwent videothoracoscopic thymectomy from June 2002 to September 2009. Sixty
      one patients (33.7%) were discharged on the next morning. Univariate and
      multivariate analyses were evaluated to determine the predictors for NMD. Mean
      calculated variables were: age (29.8 years), duration of symptoms (22.5 months),
      duration of surgery (51.3 min), postoperative stay (2.1) days, and visual
      analogue scale (2.1). No mortality occurred. Four patients were required to stay
      in intensive care unit (ICU) with a mean of 18.6 h. With logistic regression
      analysis, duration of operation (DoO) was calculated to be the only predictive
      factor for NMD (P=0.006). Video-assisted thoracoscopic thymectomy (VAT
      thymectomy) is a safe surgery procedure with a smooth postoperative period for
      MG. Although a detailed analysis was performed, only DoO was found to be a
      predictive factor for NMD in MG patients.

PMID- 19770135
TI  - A technique of an upper V-type ministernotomy in the second intercostal space.
AB  - Since cardiac surgeons found themselves able to offer a less invasive access to
      heart and great vessels, one of the first techniques to satisfy the tendency of
      minimizing the surgical trauma during general cardiac surgical procedure was a
      ministernotomy. In the current paper, we present the technique of V-type
      ministernotomy in the 2nd intercostal space, which has been employed in our
      department from June 2007 in 85 consecutive patients (mean age: 58+/-18 years);
      those operations consisted of the aortic valve replacement (AVR), surgery of the
      ascending aorta and epiaortic arterial segment.

PMID- 19770136
TI  - In patients with first-episode primary spontaneous pneumothorax is video-assisted
      thoracoscopic surgery superior to tube thoracostomy alone in terms of time to
      resolution of pneumothorax and incidence of recurrence?
AB  - A best evidence topic in cardiac surgery was written according to a structured
      protocol. The question addressed whether video-assisted thoracoscopic surgery
      (VATS) was justifiable for first-episode primary spontaneous pneumothorax (PSP).
      Altogether 183 papers were found using the reported search, of which nine
      represented the best evidence to answer the clinical question. The authors,
      journal, date and country of publication, patient group studied, study type,
      relevant outcomes and results of these papers are tabulated. We conclude that
      VATS has superior outcomes in terms of recurrence rates of pneumothorax (from 0
      to 13% according to several studies for VATS vs. 22.8 to 42% for tube
      thoracostomy alone), duration of chest tube drainage (CTD) (4.56 vs.7.6 days) and
      mean hospital stay (from 2.4 to 7.8 days vs. 6 to 12 days for CTD) with first
      episode PSP compared with conservative treatment. Additionally, even if VATS is
      associated with an average increased cost of $408, this is mitigated by the
      reduced length of stay and decreased pneumothorax recurrence, both resulting in a
      reduction of cost of 42% compared to conservative approach. These findings were
      not replicated in an article considering primary VATS (PV) vs. secondary VATS
      (SV) as the best treatment modality for PSP in children. Although the total
      treatment length of stay was significantly shorter for PV vs. SV (7.1+/-0.96 vs.
      10.5+/-1.2, P=0.04), morbidity from recurrent pneumothorax after VATS occurred
      more frequently after PV than SV (4/14 vs. 0/20, P<0.05). In this article the
      observed recurrence rate was 54%. Performing PV on all patients with PSP would
      increase cost by $4010 per patient and require a recurrence rate of 72% or more
      to financially justify this approach, therefore, the increased morbidity and cost
      do not justify a strategy of PV blebectomy/pleurodesis in children with
      spontaneous pneumothorax (SP). Instead, secondary treatment is recommended.
      Lastly, two articles also examined the rate of recurrence of VATS compared to
      open thoracotomy (OT). The range was from 0 to 7.7% for OT vs. 10.3 to 13% for
      VATS, a non-statistical difference.

PMID- 19770137
TI  - Up to twenty-five-year survival after aortic valve replacement with size 19 mm
      valves.
AB  - Long-term survival was investigated in 202 patients who underwent isolated aortic
      valve replacement (AVR) with 19 mm valves. There were 171 women with a mean age
      of 69+/-9 years and 31 men with a mean age of 64+/-13 years. Patients had a mean
      body surface area of 1.61+/-0.13 m(2). Patient-prosthesis mismatch was moderate
      in 196 and severe in six patients. The mean follow-up for all patients was 78
      months. There were 79 late deaths. The actuarial survival rates for all patients
      were 95+/-1% at 1 year, 75+/-2% at 5 years, 56+/-2% at 10 years, 41+/-2% at 15
      years, 34+/-3% at 20 years and 34+/-2% at 25 years. Patients over 70 years old
      had a lower survival rate (P=0.0001). There were significant differences between
      ejection fraction (EF) >55% and EF <55% (P=0.0305). AVR with 19 mm valves
      appeared to provide satisfactory mid-term survival. Age and low EF were risk
      factors for shorter survival.

PMID- 19770138
TI  - Splenic tear causing a hemoperitoneum after cardiac surgery.
AB  - Hemoperitoneum after cardiac surgery is a very rare but life-threatening
      complication. We have only found a few cases described in the literature, in
      which the intra-abdominal hemorrhages were caused by liver bleeding, due to
      direct hepatic trauma or spontaneous hepatic rupture. We describe the first case
      of hemoperitoneum caused by a spontaneous rupture of the spleen.

PMID- 19770139
TI  - Overview of organic memory devices.
AB  - The demand for more efficient and faster memory structures is greater today than
      ever before. The efficiency of memory structures is measured in terms of storage
      capacity and the speed of functioning. However, the production cost of such
      configurations is the natural constraint on how much can be achieved. Organic
      memory devices (OMDs) provide an ideal solution, in being inexpensive, and at the
      same time promising high performance. However, all OMDs reported so far suffer
      from multiple drawbacks that render their industrial implementation premature.
      This article introduces the different types of OMDs, discusses the progress in
      this field over the last 9 years and invokes conundrums that scholars of this
      field are currently faced with, such as questions about the charging mechanism
      and stability of devices, contradictions in the published work and some future
      directions.

PMID- 19770140
TI  - Multi-layer stackable polymer memory devices.
AB  - Multi-layer stackable polymer memory architecture is an interesting new direction
      for polymer memory. The memory density can be increased by increasing the number
      of stacked layers without reducing the minimum feature size. To achieve multi
      level stacking, the polymer used must be able to be cross-linked so that it will
      not be dissolved upon deposition of additional layers. This requirement also
      makes the polymer robust enough to withstand conventional lithographic processes.
      In this paper, the various approaches to achieve cross-linkable polymer memory
      are discussed. Device fabrication and performance are also reported.

PMID- 19770141
TI  - From silicon to organic nanoparticle memory devices.
AB  - After introducing the operational principle of nanoparticle memory devices, their
      current status in silicon technology is briefly presented in this work. The
      discussion then focuses on hybrid technologies, where silicon and organic
      materials have been combined together in a nanoparticle memory device, and
      finally concludes with the recent development of organic nanoparticle memories.
      The review is focused on the nanoparticle memory concept as an extension of the
      current flash memory device. Organic nanoparticle memories are at a very early
      stage of research and have not yet found applications. When this happens, it is
      expected that they will not directly compete with mature silicon technology but
      will find their own areas of application.

PMID- 19770142
TI  - Enhancement of electrical bistability through semiconducting nanoparticles for
      organic memory applications.
AB  - We report that an enhancement in electrical bistability in devices based on
      organic molecules can be achieved by the introduction of semiconducting
      nanoparticles. Here, devices based on alternate layers of a dye in the xanthene
      class and CdSe nanoparticles have been compared with devices based on the
      individual components. Results from dye/CdSe devices have yielded an appreciable
      enhancement in electrical bistability compared with those based on the dye or the
      nanoparticles. The enhancement is due to augmented carrier transport through the
      nanoparticles to the dye that consequently undergoes a change in its
      conformation, having a higher conductivity. We have evidenced read-only and
      random-access memory applications in the dye/nanoparticle hybrid system.

PMID- 19770143
TI  - Electrodeposition of copper tetracyanoquinodimethane for bipolar resistive
      switching non-volatile memories.
AB  - Electrodeposition experiments of the charge-transfer complex copper
      tetracyanoquinodimethane (CuTCNQ) (where TCNQ denotes 7,7',8,8'
      tetracyanoquinodimethane) on noble metal electrodes (M=Pt and Au) were optimized
      in order to produce suitable layers for bipolar resistive switching cross-bar
      M/CuTCNQ/Al memory cells. Corresponding memories exhibited up to more than 10 000
      consecutive write/erase cycles, with very stable on and off reading currents and
      an on/off current ratio of 10. CuTCNQ electrodeposition techniques were
      furthermore optimized for growing the material in 250 nm diameter contact holes
      of complementary metal oxide semiconductor dies with tungsten bottom contacts.

PMID- 19770144
TI  - Tristable electrical conductivity switching in a polyfluorene-diphenylpyridine
      copolymer with pendant carbazole groups.
AB  - Tristable electrical conductivity switching and non-volatile memory effects are
      demonstrated in a conjugated copolymer of poly(2,6-diphenyl-4-((9-ethyl)-9H
      carbazole)-pyridinyl-alt-2,7-(9,9-didodecyl)-9H-fluorenyl) (PPCzPF). The indium
      tin oxide (ITO)/PPCzPF/Al device can be switched from the low-conductivity (off)
      state to the first high-conductivity (on-1) state at 1.8 V, with an on/off
      current ratio of approximately 100. The device can be further switched from the
      on-1 state to the next higher conductivity (on-2) state at 2.4 V, with an on-2/on
      1 current ratio of approximately 20. All the three conductivity states are
      accessible, stable and non-erasable. The tri-level conductance switching can be
      explained in terms of field-induced conformational ordering of the polymer chains
      and enhanced charge-transfer interaction at the PPCzPF/ITO interface.

PMID- 19770145
TI  - Gold nanoparticle charge trapping and relation to organic polymer memory devices.
AB  - Nanoparticle-based polymer memory devices (PMDs) are a promising technology that
      could replace conventional silicon-based electronic memory, offering fast
      operating speeds, simple device structures and low costs. Here we report on the
      current state of nanoparticle PMDs and review some of the problems that are still
      present in the field. We also present new data regarding the charging of gold
      nanoparticles in metal-insulator-semiconductor capacitors, showing that charging
      is possible under the application of an electric field with a trapped charge
      density due to the nanoparticles of 3.3 x 10(12) cm(-2).

PMID- 19770146
TI  - Electrical bistability in a composite of polymer and barium titanate
      nanoparticles.
AB  - Growth in the use of organic materials in the fabrication of electronic devices
      is on the rise. Recently, some attempts have been undertaken to manufacture
      polymer memory devices. Such devices are fabricated by depositing a blend (an
      admixture of organic polymer, small organic molecules and nanoparticles) between
      two metal electrodes. These devices show two electrical conductivity states
      ('high' and 'low') when a voltage is applied, thus rendering the structures
      suitable for data retention. In this paper, we describe an attempt to fabricate
      memory devices using ferroelectric nanoparticles embedded in an organic polymer.
      This paper also discusses issues related to the observed memory effect.

PMID- 19770147
TI  - Population growth in retrospect and prospect.

PMID- 19770149
TI  - Population priorities: the challenge of continued rapid population growth.
AB  - Rapid population growth continues in the least developed countries. The
      revisionist case that rapid population could be overcome by technology, that
      population density was advantageous, that capital shallowing is not a vital
      concern and that empirical investigations had not proved a correlation between
      high population growth and low per capita income was both empirically and
      theoretically flawed. In the modern world, population density does not play the
      role it did in nineteenth-century Europe and rates of growth in some of today's
      least developed nations are four times than those in nineteenth-century Europe,
      and without major accumulation of capital per capita, no major economy has or is
      likely to make the low- to middle-income transition. Though not sufficient,
      capital accumulation for growth is absolutely essential to economic growth. While
      there are good reasons for objecting to the enforced nature of the Chinese one
      child policy, we should not underestimate the positive impact which that policy
      has almost certainly had and will have over the next several decades on Chinese
      economic performance. And a valid reticence about telling developing countries
      that they must contain fertility should not lead us to underestimate the severely
      adverse impact of high fertility rates on the economic performance and prospects
      of many countries in Africa and the Middle East.

PMID- 19770150
TI  - Human population growth and the demographic transition.
AB  - The world and most regions and countries are experiencing unprecedentedly rapid
      demographic change. The most obvious example of this change is the huge expansion
      of human numbers: four billion have been added since 1950. Projections for the
      next half century expect a highly divergent world, with stagnation or potential
      decline in parts of the developed world and continued rapid growth in the least
      developed regions. Other demographic processes are also undergoing extraordinary
      change: women's fertility has dropped rapidly and life expectancy has risen to
      new highs. Past trends in fertility and mortality have led to very young
      populations in high fertility countries in the developing world and to
      increasingly older populations in the developed world. Contemporary societies are
      now at very different stages of their demographic transitions. This paper
      summarizes key trends in population size, fertility and mortality, and age
      structures during these transitions. The focus is on the century from 1950 to
      2050, which covers the period of most rapid global demographic transformation.

PMID- 19770151
TI  - Stall in fertility decline in Eastern African countries: regional analysis of
      patterns, determinants and implications.
AB  - We use data from the Demographic and Health Surveys to examine the patterns of
      stall in fertility decline in four Eastern African countries. Contrary to
      patterns of fertility transition in Africa that cut across various socio-economic
      and geographical groups within countries, we find strong selectivity of fertility
      stall across different groups and regions in all four countries. In both Kenya
      and Tanzania where fertility decline has stalled at the national level, it
      continued to decline among the most educated women and in some regions. While
      fertility has remained at pre-transition level in Uganda over the past 20 years,
      there are signs of decline with specific groups of women (especially the most
      educated, urban and those in the Eastern region) taking the lead. For Zimbabwe,
      although fertility has continued to decline at the national level, stall is
      observed among women with less than secondary education and those in some of the
      regions. We link these intra-country variations to differential changes in socio
      economic variables, family planning programme environment and reproductive
      behaviour models. The results suggest that declines in contraceptive use,
      increases in unmet need for family planning, increasing preferences for larger
      families, and increases in adolescent fertility were consistently associated with
      stalls in subgroup fertility across all four countries. These results are
      consistent with models that emphasize the role of declines in national and
      international commitments to family planning programmes in the premature stall in
      sub-Saharan fertility transition.

PMID- 19770152
TI  - Population ageing: what should we worry about?
AB  - Approximately half the world's population now has replacement-level fertility or
      below. The UK experience in accommodating to a changing dependency ratio provides
      some generalizable insights. A mechanistic approach assuming a fixed retirement
      age and a need to raise fertility or increase immigration in order to maintain
      pensions at a fixed proportion of the gross domestic product (GDP) is overstated
      and wrong. It needs to be replaced by a welfare optimizing model, which takes
      into account the increasing years of healthy life, a slow rise in the pensionable
      age, capital inheritance and wider welfare considerations of population density
      that are not reflected in GDP measures. A combined replacement ratio (CRR) is
      suggested for developed countries combining the impact of the fertility rate and
      immigration rate. A CRR above 2 implies continued population growth. The current
      UK CRR of 2.48 is higher than needed for pension reasons, and it is suggested
      that it exceeds the welfare maximizing level.

PMID- 19770153
TI  - Population, poverty and economic development.
AB  - Economists, demographers and other social scientists have long debated the
      relationship between demographic change and economic outcomes. In recent years,
      general agreement has emerged to the effect that improving economic conditions
      for individuals generally lead to lower birth rates. But, there is much less
      agreement about the proposition that lower birth rates contribute to economic
      development and help individuals and families to escape from poverty. The paper
      examines recent evidence on this aspect of the debate, concludes that the burden
      of evidence now increasingly supports a positive conclusion, examines recent
      trends in demographic change and economic development and argues that the
      countries representing the last development frontier, those of Sub-Saharan
      Africa, would be well advised to incorporate policies and programmes to reduce
      high fertility in their economic development strategies.

PMID- 19770154
TI  - Sola schola et sanitate: human capital as the root cause and priority for
      international development?
AB  - This paper summarizes new scientific evidence supporting the hypothesis that
      among the many factors contributing to international development, the combination
      of education and health stands out as a root cause on which other dimensions of
      development depend. Much of this recent analysis is based on new reconstructions
      and projections of populations by age, sex and four levels of educational
      attainment for more than 120 countries using the demographic method of multi
      state population dynamics. It also refers to a series of systems analytical
      population-development-environment case studies that comprehensively assess the
      role of population and education factors relative to other factors in the
      struggle for sustainable development. The paper also claims that most concerns
      about the consequences of population trends are in fact concerns about human
      capital, and that only by adding the 'quality' dimension of education to the
      traditionally narrow focus on size and age structure can some of the long
      standing population controversies be resolved.

PMID- 19770155
TI  - Population policies, programmes and the environment.
AB  - Human consumption is depleting the Earth's natural resources and impairing the
      capacity of life-supporting ecosystems. Humans have changed ecosystems more
      rapidly and extensively over the past 50 years than during any other period,
      primarily to meet increasing demands for food, fresh water, timber, fibre and
      fuel. Such consumption, together with world population increasing from 2.6
      billion in 1950 to 6.8 billion in 2009, are major contributors to environmental
      damage. Strengthening family-planning services is crucial to slowing population
      growth, now 78 million annually, and limiting population size to 9.2 billion by
      2050. Otherwise, birth rates could remain unchanged, and world population would
      grow to 11 billion. Of particular concern are the 80 million annual pregnancies
      (38% of all pregnancies) that are unintended. More than 200 million women in
      developing countries prefer to delay their pregnancy, or stop bearing children
      altogether, but rely on traditional, less-effective methods of contraception or
      use no method because they lack access or face other barriers to using
      contraception. Family-planning programmes have a successful track record of
      reducing unintended pregnancies, thereby slowing population growth. An estimated
      $15 billion per year is needed for family-planning programmes in developing
      countries and donors should provide at least $5 billion of the total, however,
      current donor assistance is less than a quarter of this funding target.

PMID- 19770156
TI  - Traversing the mountaintop: world fossil fuel production to 2050.
AB  - During the past century, fossil fuels--petroleum liquids, natural gas and coal-
      were the dominant source of world energy production. From 1950 to 2005, fossil
      fuels provided 85-93% of all energy production. All fossil fuels grew
      substantially during this period, their combined growth exceeding the increase in
      world population. This growth, however, was irregular, providing for rapidly
      growing per capita production from 1950 to 1980, stable per capita production
      from 1980 to 2000 and rising per capita production again after 2000. During the
      past half century, growth in fossil fuel production was essentially limited by
      energy demand. During the next half century, fossil fuel production will be
      limited primarily by the amount and characteristics of remaining fossil fuel
      resources. Three possible scenarios--low, medium and high--are developed for the
      production of each of the fossil fuels to 2050. These scenarios differ primarily
      by the amount of ultimate resources estimated for each fossil fuel. Total fossil
      fuel production will continue to grow, but only slowly for the next 15-30 years.
      The subsequent peak plateau will last for 10-15 years. These production peaks are
      robust; none of the fossil fuels, even with highly optimistic resource estimates,
      is projected to keep growing beyond 2050. World fossil fuel production per capita
      will thus begin an irreversible decline between 2020 and 2030.

PMID- 19770157
TI  - Considering population and war: a critical and neglected aspect of conflict
      studies.
AB  - This study analyses the relationship between war and population. The impact of
      the growth and decline of population on important types of warfare--great power,
      small power, civil war as well as terrorism--is illustrated, with the objective
      in each case to be descriptive of risk. I find that population change has a
      significant impact on each, with the greatest causal impact on small power
      conflicts, civil war and upon terrorism. I conclude with some reasons for guarded
      optimism about the incorporation of population as a component of analysis in the
      discipline of international studies, and for the potential to devise new
      solutions to prevent conflict.

PMID- 19770158
TI  - Making family planning accessible in resource-poor settings.
AB  - It is imperative to make family planning more accessible in low resource
      settings. The poorest couples have the highest fertility, the lowest
      contraceptive use and the highest unmet need for contraception. It is also in the
      low resource settings where maternal and child mortality is the highest. Family
      planning can contribute to improvements in maternal and child health, especially
      in low resource settings where overall access to health services is limited. Four
      critical steps should be taken to increase access to family planning in resource
      poor settings: (i) increase knowledge about the safety of family planning
      methods; (ii) ensure contraception is genuinely affordable to the poorest
      families; (iii) ensure supply of contraceptives by making family planning a
      permanent line item in healthcare system's budgets and (iv) take immediate action
      to remove barriers hindering access to family planning methods. In Africa, there
      are more women with an unmet need for family planning than women currently using
      modern methods. Making family planning accessible in low resource settings will
      help decrease the existing inequities in achieving desired fertility at
      individual and country level. In addition, it could help slow population growth
      within a human rights framework. The United Nations Population Division
      projections for the year 2050 vary between a high of 10.6 and a low of 7.4
      billion. Given that most of the growth is expected to come from today's resource
      poor settings, easy access to family planning could make a difference of billions
      in the world in 2050.

PMID- 19770159
TI  - The theoretical and political framing of the population factor in development.
AB  - The silence about population growth in recent decades has hindered the ability of
      those concerned with ecological change, resource scarcity, health and educational
      systems, national security, and other global challenges to look with maximum
      objectivity at the problems they confront. Two central questions about population
      -(1) is population growth a problem? and (2) what causes fertility decline?--are
      often intertwined; if people think the second question implies possible coercion,
      or fear of upsetting cultures, they can be reluctant to talk about the first. The
      classic and economic theories explaining the demographic transition assume that
      couples want many children and they make decisions to have a smaller family when
      some socio-economic change occurs. However, there are numerous anomalies to this
      explanation. This paper suggests that the societal changes are neither necessary
      nor sufficient for family size to fall. Many barriers of non-evidence-based
      restrictive medical rules, cost, misinformation and social traditions exist
      between women and the fertility regulation methods and correct information they
      need to manage their family size. When these barriers are reduced, birth rates
      tend to decline. Many of the barriers reflect a patriarchal desire to control
      women, which can be largely explained by evolutionary biology. The theoretical
      explanations of fertility should (i) attach more weight to the many barriers to
      voluntary fertility regulation, (ii) recognize that a latent desire to control
      fertility may be far more prevalent among women than previously understood, and
      (iii) appreciate that women implicitly and rationally make benefit-cost analyses
      based on the information they have, wanting modern family planning only after
      they understand it is a safe option. Once it is understood that fertility can be
      lowered by purely voluntary means, comfort with talking about the population
      factor in development will rise.

PMID- 19770160
TI  - Where next?
AB  - This paper provides a personal perspective on the rich discussions at the Bixby
      Forum. The size, rate of growth and age structure of the human population
      interact with many other key factors, from environmental change to governance.
      While the details of future interactions are sometimes difficult to predict,
      taken together they pose sombre threats to a socially and economically
      sustainable future for the rich and to any realistic possibility of lifting the
      world's bottom two billion people out of poverty. Adaptive changes will be needed
      to cope with an ageing population in countries with low fertility or below, but
      these are achievable. More worrying, continued rapid population growth in many of
      the least developed countries could lead to hunger, a failure of education to
      keep pace with growing numbers, and conflict. The assumption that the demographic
      transition from high to low birth rates occurs as a result of exogenous social
      and economic forces is being replaced by a clearer understanding of the many
      barriers that separate women from the knowledge and technologies they need to
      manage their childbearing within a human rights framework. The forum ended with a
      clear consensus that much more emphasis needs to be given to meeting the need for
      family planning and to investing in education.

PMID- 19770161
TI  - Retinal imaging using commercial broadband optical coherence tomography.
AB  - AIMS: To examine the practical improvement in image quality afforded by a
      broadband light source in a clinical setting and to define image quality metrics
      for future use in evaluating spectral domain optical coherence tomography (SD
      OCT) images. METHODS: A commercially available SD-OCT system, configured with a
      standard source as well as an external broadband light source, was used to
      acquire 4 mm horizontal line scans of the right eye of 10 normal subjects. Scans
      were averaged to reduce speckling and multiple retinal layers were analysed in
      the resulting images. RESULTS: For all layers there was a significant improvement
      in the mean local contrast (average improvement by a factor of 1.66) when using
      the broadband light source. Intersession variability was shown not to be a major
      contributing factor to the observed improvement in image quality obtained with
      the broadband light source. We report the first observation of sublamination
      within the inner plexiform layer visible with SD-OCT. CONCLUSION: The practical
      improvement with the broadband light source was significant, although it remains
      to be seen what the utility will be for diagnostic pathology. The approach
      presented here serves as a model for a more quantitative analysis of SD-OCT
      images, allowing for more meaningful comparisons between subjects, clinics and SD
      OCT systems.

PMID- 19770162
TI  - Stop using the Ashworth Scale for the assessment of spasticity.
AB  - AIM: Many studies have been performed on the methodological qualities of the
      (modified) Ashworth Scale but overall these studies seem inconclusive. The aim of
      this study was to investigate the construct validity and inter-rater reliability
      of the Ashworth Scale (AS) for the assessment of spasticity in the upper and
      lower extremities. METHOD: A cross-sectional study on spasticity in the elbow
      flexors (part 1) and knee extensors (part 2) was carried out. In both parts AS
      was assessed while muscle activity and resistance were recorded simultaneously in
      patients with upper motor neuron syndrome. Each patient was measured by three
      raters. RESULTS: 30 patients participated, 19 in each part of the study. For
      elbow flexor muscles, AS was not significantly associated with electromyographic
      parameters, except for rater 2 (rho = 0.66, p<0.01). A significant moderate
      association was found with resistance (0.54< or = rho < or =0.61, p<0.05). For
      knee extensors, AS scores were moderately associated with muscle activity (0.56<
      or = rho < or =0.66, p<0.05) and also with resistance (0.55< or = rho < or =0.87,
      p<0.05). The intraclass correlation coefficient for absolute agreement was 0.58
      for elbow flexors and 0.63 for knee extensors. In linear mixed model analysis,
      the factor rater appeared to be highly associated with AS. CONCLUSION: The
      validity and reliability of the AS is insufficient to be used as a measure of
      spasticity.

PMID- 19770163
TI  - Use of drugs with anticholinergic effect and impact on cognition in Parkinson's
      disease: a cohort study.
AB  - BACKGROUND: Cognitive decline is common in Parkinson's disease (PD). Although
      some of the aetiological factors are known, it is not yet known whether drugs
      with anticholinergic activity (AA) contribute to this cognitive decline. Such
      knowledge would provide opportunities to prevent acceleration of cognitive
      decline in PD. OBJECTIVE: To study whether the use of agents with anticholinergic
      properties is an independent risk factor for cognitive decline in patients with
      PD. METHODS: A community-based cohort of patients with PD (n=235) were included
      and assessed at baseline. They were reassessed 4 and 8 years later. Cognition was
      assessed using the Mini-Mental State Examination (MMSE). A detailed assessment of
      the AA of all drugs prescribed was made, and AA was classified according to a
      standardised scale. Relationships between cognitive decline and AA load and
      duration of treatment were assessed using bivariate and multivariate statistical
      analyses. RESULTS: More than 40% used drugs with AA at baseline. During the 8
      year follow-up, the cognitive decline was higher in those who had been taking AA
      drugs (median decline on MMSE 6.5 points) compared with those who had not taken
      such drugs (median decline 1 point; p=0.025). In linear regression analyses
      adjusting for age, baseline cognition and depression, significant associations
      with decline on MMSE were found for total AA load (standardised beta=0.229,
      p=0.04) as well as the duration of using AA drugs (standardised beta 0.231,
      p=0.032). CONCLUSION: Our findings suggest that there is an association between
      anticholinergic drug use and cognitive decline in PD. This may provide an
      important opportunity for clinicians to avoid increasing progression of cognitive
      decline by avoiding drugs with AA. Increased awareness by clinicians is required
      about the classes of drugs that have anticholinergic properties.

PMID- 19770164
TI  - The role of carbohydrates in seed germination and seedling establishment of
      Himatanthus sucuuba, an Amazonian tree with populations adapted to flooded and
      non-flooded conditions.
AB  - BACKGROUND AND AIMS: In the Amazonian floodplains plants withstand annual periods
      of flooding which can last 7 months. Under these conditions seedlings remain
      submerged in the dark for long periods since light penetration in the water is
      limited. Himatanthus sucuuba is a tree species found in the 'varzea' (VZ)
      floodplains and adjacent non-flooded 'terra-firme' (TF) forests. Biochemical
      traits which enhance flood tolerance and colonization success of H. sucuuba in
      periodically flooded environments were investigated. METHODS: Storage
      carbohydrates of seeds of VZ and TF populations were extracted and analysed by
      HPAEC/PAD. Starch was analysed by enzyme (glucoamylase) degradation followed by
      quantification of glucose oxidase. Carbohydrate composition of roots of VZ and TF
      seedlings was studied after experimental exposure to a 15-d period of submersion
      in light versus darkness. KEY RESULTS: The endosperm contains a large proportion
      of the seed reserves, raffinose being the main non-structural carbohydrate.
      Around 93 % of the cell wall storage polysaccharides (percentage dry weight
      basis) in the endosperm of VZ seeds was composed of mannose, while soluble sugars
      accounted for 2.5%. In contrast, 74 % of the endosperm in TF seeds was composed
      of galactomannans, while 22 % of the endosperm was soluble sugars. This suggested
      a larger carbohydrate allocation to germination in TF populations whereas VZ
      populations allocate comparatively more to carbohydrates mobilized during
      seedling development. The concentration of root non-structural carbohydrates in
      non-flooded seedlings strongly decreased after a 15-d period of darkness, whereas
      flooded seedlings were less affected. These effects were more pronounced in TF
      seedlings, which showed significantly lower root non-structural carbohydrate
      concentrations. CONCLUSIONS: There seem to be metabolic adjustments in VZ but not
      TF seedlings that lead to adaptation to the combined stresses of darkness and
      flooding. This seems to be important for the survival of the species in these
      contrasting environments, leading these populations to different directions
      during evolution.

PMID- 19770165
TI  - Pollination biology of fruit-bearing hedgerow plants and the role of flower
      visiting insects in fruit-set.
AB  - BACKGROUND AND AIMS: In the UK, the flowers of fruit-bearing hedgerow plants
      provide a succession of pollen and nectar for flower-visiting insects for much of
      the year. The fruits of hedgerow plants are a source of winter food for
      frugivorous birds on farmland. It is unclear whether recent declines in
      pollinator populations are likely to threaten fruit-set and hence food supply for
      birds. The present study investigates the pollination biology of five common
      hedgerow plants: blackthorn (Prunus spinosa), hawthorn (Crataegus monogyna), dog
      rose (Rosa canina), bramble (Rubus fruticosus) and ivy (Hedera helix). METHODS:
      The requirement for insect pollination was investigated initially by excluding
      insects from flowers by using mesh bags and comparing immature and mature fruit
      set with those of open-pollinated flowers. Those plants that showed a requirement
      for insect pollination were then tested to compare fruit-set under two additional
      pollination service scenarios: (1) reduced pollination, with insects excluded
      from flowers bagged for part of the flowering period, and (2) supplemental
      pollination, with flowers hand cross-pollinated to test for pollen limitation.
      KEY RESULTS: The proportions of flowers setting fruit in blackthorn, hawthorn and
      ivy were significantly reduced when insects were excluded from flowers by using
      mesh bags, whereas fruit-set in bramble and dog rose were unaffected. Restricting
      the exposure of flowers to pollinators had no significant effect on fruit-set.
      However, blackthorn and hawthorn were found to be pollen-limited, suggesting that
      the pollination service was inadequate in the study area. CONCLUSIONS: Ensuring
      strong populations of insect pollinators may be essential to guarantee a winter
      fruit supply for birds in UK hedgerows.

PMID- 19770166
TI  - Effect of m-3M3FBS on Ca(2+) movement in Madin-Darby canine renal tubular cells.
AB  - The effect of 2,4,6-trimethyl-N-(meta-3-trifluoromethyl-phenyl)
      benzenesulfonamide (m-3M3FBS), a presumed phospholipase C (PLC) activator, on
      cytosolic free Ca(2+) concentrations ([Ca( 2+)](i)) in Madin-Darby canine kidney
      (MDCK) cells is unclear. This study explored whether m-3M3FBS changed basal
      [Ca(2+)](i) levels in suspended MDCK cells using fura-2 as a Ca(2+)-sensitive
      fluorescent dye. M-3M3FBS at concentrations between 0.1 and 20 microM increased
      [Ca(2+)](i) in a concentration-dependent manner. The Ca(2+) signal was decreased
      by removing extracellular Ca(2+). M-3M3FBS-induced Ca(2+) influx was inhibited by
      the store-operated Ca(2+) channel blockers nifedipine, econazole, and SK&F96365,
      and by the phospholipase A2 inhibitor aristolochic acid. In Ca(2+)-free medium,
      20-microM m-3M3FBS pretreatment abolished the [Ca(2+)](i) rise induced by the
      endoplasmic reticulum Ca(2+) pump inhibitors thapsigargin (TG) and cyclopiazonic
      acid (CPA). Conversely, pretreatment with TG or CPA partly reduced m-3M3FBS
      induced [Ca(2+)](i) rise. The inhibition of PLC with U73122 did not alter m
      3M3FBS-induced [Ca(2+)](i) rise. Collectively, in MDCK cells, m-3M3FBS induced
      [Ca(2+)](i) rises by causing PLC-independent Ca(2+) release from the endoplasmic
      reticulum and Ca(2+) influx via store-operated Ca(2+) channels and other
      unidentified Ca(2+) channels.

PMID- 19770167
TI  - In-depth qualitative and quantitative profiling of tyrosine phosphorylation using
      a combination of phosphopeptide immunoaffinity purification and stable isotope
      dimethyl labeling.
AB  - Several mass spectrometry-based assays have emerged for the quantitative
      profiling of cellular tyrosine phosphorylation. Ideally, these methods should
      reveal the exact sites of tyrosine phosphorylation, be quantitative, and not be
      cost-prohibitive. The latter is often an issue as typically several milligrams of
      (stable isotope-labeled) starting protein material are required to enable the
      detection of low abundance phosphotyrosine peptides. Here, we adopted and refined
      a peptidecentric immunoaffinity purification approach for the quantitative
      analysis of tyrosine phosphorylation by combining it with a cost-effective stable
      isotope dimethyl labeling method. We were able to identify by mass spectrometry,
      using just two LC-MS/MS runs, more than 1100 unique non-redundant phosphopeptides
      in HeLa cells from about 4 mg of starting material without requiring any further
      affinity enrichment as close to 80% of the identified peptides were tyrosine
      phosphorylated peptides. Stable isotope dimethyl labeling could be incorporated
      prior to the immunoaffinity purification, even for the large quantities (mg) of
      peptide material used, enabling the quantification of differences in tyrosine
      phosphorylation upon pervanadate treatment or epidermal growth factor
      stimulation. Analysis of the epidermal growth factor-stimulated HeLa cells, a
      frequently used model system for tyrosine phosphorylation, resulted in the
      quantification of 73 regulated unique phosphotyrosine peptides. The quantitative
      data were found to be exceptionally consistent with the literature, evidencing
      that such a targeted quantitative phosphoproteomics approach can provide
      reproducible results. In general, the combination of immunoaffinity purification
      of tyrosine phosphorylated peptides with large scale stable isotope dimethyl
      labeling provides a cost-effective approach that can alleviate variation in
      sample preparation and analysis as samples can be combined early on. Using this
      approach, a rather complete qualitative and quantitative picture of tyrosine
      phosphorylation signaling events can be generated.

PMID- 19770168
TI  - Simplified cell culture method for the diagnosis of atypical primary ciliary
      dyskinesia.
AB  - BACKGROUND: The diagnosis of primary ciliary dyskinesia (PCD) can be challenging,
      and it may be particularly difficult to distinguish primary ciliary disease from
      the secondary changes after infections. OBJECTIVES: The purpose of the study was
      to evaluate if nasal epithelial cells, obtained with nasal brushing instead of a
      biopsy, could be used in a culture system for the diagnosis of PCD in difficult
      cases. METHODS AND MAIN RESULTS: Ciliary motion analysis (CMA) and transmission
      electron microscopy (TEM) were performed on 59 subjects with persistent or
      recurrent pneumonia. These investigations allowed the diagnosis of PCD in 13
      (22%) patients while the defect of the cilia was considered secondary to
      infections in 37 (63%) subjects. In the remaining nine (15%) patients the
      diagnostic evaluation with CMA and TEM remained inconclusive. Ciliogenesis in
      culture allowed the diagnosis of PCD in four of these patients, it was indicative
      of a secondary defect in two subjects, and it was not helpful in the remaining
      three patients. CONCLUSIONS: Culture of cells obtained with brushing of the nasal
      turbinate is not a perfect test, nevertheless it may offer diagnostic help in
      doubtful cases of PCD.

PMID- 19770170
TI  - Do substantia nigra dopaminergic neurons differentiate between reward and
      punishment?
AB  - The activity of dopaminergic neurons are thought to be increased by stimuli that
      predict reward and decreased by stimuli that predict aversive outcomes. Recent
      work by Matsumoto and Hikosaka challenges this model by asserting that stimuli
      associated with either rewarding or aversive outcomes increase the activity of
      dopaminergic neurons in the substantia nigra pars compacta.

PMID- 19770169
TI  - Body mass index is associated with the development of acute respiratory distress
      syndrome.
AB  - BACKGROUND: The relationship between body mass index (BMI) and development of
      acute respiratory distress syndrome (ARDS) is unknown. METHODS: A cohort study of
      critically ill patients at risk for ARDS was carried out. BMI was calculated from
      admission height and weight. Patients were screened daily for AECC (American
      European Consensus Committee)-defined ARDS and 60-day ARDS mortality. RESULTS: Of
      1795 patients, 83 (5%) patients were underweight (BMI <18.5 kg/m(2)), 627 (35%)
      normal (BMI 18.5-24.9), 605 (34%) overweight (BMI 25-29.9), 364 (20%) obese (BMI
      30-39.9) and 116 (6%) severely obese (BMI > or =40). Increasing weight was
      associated with younger age (p<0.001), diabetes (p<0.0001), higher blood glucose
      (p<0.0001), lower prevalence of direct pulmonary injury (p<0.0001) and later
      development of ARDS (p = 0.01). BMI was associated with ARDS on multivariate
      analysis (OR(adj) 1.24 per SD increase; 95% CI 1.11 to 1.39). Similarly, obesity
      was associated with ARDS compared with normal weight (OR(adj) 1.66; 95% CI 1.21
      to 2.28 for obese; OR(adj) 1.78; 95% CI 1.12 to 2.92 for severely obese).
      Exploratory analysis in a subgroup of intubated patients without ARDS on
      admission (n = 1045) found that obese patients received higher peak (p<0.0001)
      and positive end-expiratory pressures (p<0.0001) than non-obese patients. Among
      patients with ARDS, increasing BMI was associated with increased length of stay
      (p = 0.007) but not with mortality (OR(adj) 0.89 per SD increase; 95% CI 0.71 to
      1.12). CONCLUSION: BMI was associated with increased risk of ARDS in a weight
      dependent manner and with increased length of stay, but not with mortality.
      Additional studies are needed to determine whether differences in initial
      ventilator settings may contribute to ARDS development in the obese.

PMID- 19770171
TI  - Connected kids at Head Start: taking office-based violence prevention to the
      community.
AB  - OBJECTIVE: The goal was to assess the acceptability and appropriateness of using
      a violence prevention curriculum, Connected Kids: Safe, Strong, Secure, at Head
      Start centers. METHODS: Eight 90-minute focus groups (4 parent groups and 4
      family advocate groups) were conducted at 2 Head Start centers. Each discussion
      was audiotaped, transcribed, and analyzed for major themes. RESULTS: A total of
      63 adults (38 family advocates [92% female] and 25 parents [100% female])
      participated in the 8 groups. Family advocates and parents agreed that Head Start
      was an important source of parenting advice and of referrals to community
      resources. Connected Kids topics were well received, although potential parental
      resistance to gun safety and discipline materials was identified. The positive
      nature of the advice was important to both types of groups. Brochures were
      generally well liked, but all groups thought that they should be linked directly
      to community resource information and offered as part of tailored education.
      Various venues for curriculum use were suggested, and formats involving multiple
      media were requested. Although Head Start serves preschool-aged children, parents
      and family advocates valued access to the full range of Connected Kids materials
      (for ages 0 -18 years). Family advocates emphasized that supplementary materials
      on background information and delivery methods would be essential for effective
      implementation of Connected Kids at Head Start. CONCLUSIONS: Head Start family
      advocates and parents found the Connected Kids curriculum desirable. Although
      modifications might improve its usefulness, the curriculum seems acceptable and
      appropriate for the Head Start environment.

PMID- 19770173
TI  - When should children be tested for genetic diseases?

PMID- 19770172
TI  - Joint policy statement--guidelines for care of children in the emergency
      department.
AB  - Children who require emergency care have unique needs, especially when
      emergencies are serious or life-threatening. The majority of ill and injured
      children are brought to community hospital emergency departments (EDs) by virtue
      of their geography within communities. Similarly, emergency medical services
      (EMS) agencies provide the bulk of out-of-hospital emergency care to children. It
      is imperative, therefore, that all hospital EDs have the appropriate resources
      (medications, equipment, policies, and education) and staff to provide effective
      emergency care for children. This statement outlines resources necessary to
      ensure that hospital EDs stand ready to care for children of all ages, from
      neonates to adolescents. These guidelines are consistent with the recommendations
      of the Institute of Medicine's report on the future of emergency care in the
      United States health system. Although resources within emergency and trauma care
      systems vary locally, regionally, and nationally, it is essential that hospital
      ED staff and administrators and EMS systems' administrators and medical directors
      seek to meet or exceed these guidelines in efforts to optimize the emergency care
      of children they serve. This statement has been endorsed by the Academic
      Pediatric Association, American Academy of Family Physicians, American Academy of
      Physician Assistants, American College of Osteopathic Emergency Physicians,
      American College of Surgeons, American Heart Association, American Medical
      Association, American Pediatric Surgical Association, Brain Injury Association of
      America, Child Health Corporation of America, Children's National Medical Center,
      Family Voices, National Association of Children's Hospitals and Related
      Institutions, National Association of EMS Physicians, National Association of
      Emergency Medical Technicians, National Association of State EMS Officials,
      National Committee for Quality Assurance, National PTA, Safe Kids USA, Society of
      Trauma Nurses, Society for Academic Emergency Medicine, and The Joint Commission.

PMID- 19770174
TI  - How do we support follow-up with the primary care provider after an emergency
      department visit for asthma?

PMID- 19770175
TI  - Occupational therapy home programs for cerebral palsy: double-blind, randomized,
      controlled trial.
AB  - OBJECTIVE: The goal was to assess the effectiveness of an occupational therapy
      home program (OTHP), compared with no OTHP, with respect to function and parent
      satisfaction with child function, participation, goal attainment, and quality of
      upper limb skill in school-aged children with cerebral palsy. METHODS: Thirty-six
      children with cerebral palsy (mean age: 7.7 years; male: 69%; Gross Motor
      Function Classification System: level I, 47%; level II, 14%; level III, 16%;
      level IV, 7%; level V, 16%; spasticity, 85%; dyskinesia, 14%; ataxia, 3%) were
      randomly and equally assigned to OTHPs for 8 or 4 weeks or to no OTHP. The
      primary end point was Canadian Occupational Performance Measure scores 8 weeks
      after baseline. Secondary measures were recorded at 4 and 8 weeks. RESULTS: Eight
      weeks of OTHP produced statistically significant differences in function and
      parent satisfaction with function, compared with no OTHP. Parents in the 4-week
      OTHP group did not discontinue use at 4 weeks, as instructed, and continued for 8
      weeks; results demonstrated statistically significant differences, compared with
      no OTHP. There was no difference in primary or secondary end point measures
      between intervention groups. CONCLUSION: Pediatricians can advise families that
      OTHPs developed with a collaborative, evidence-based approach and implemented by
      parents at home were clinically effective if implemented 17.5 times per month for
      an average of 16.5 minutes per session.

PMID- 19770176
TI  - Can erythropoietin improve developmental outcomes for preterm infants?

PMID- 19770177
TI  - PPAR control: it's SIRTainly as easy as PGC.
AB  - This review describes recent advances in our knowledge of the regulatory
      interactions influencing the expression of peroxisome proliferator-activated
      receptor (PPAR)-regulated genes. We address recent advances highlighting the role
      of PPARgamma (PPARG) coactivator-1 (PGC-1) and lipin-1 in co-ordinating the
      expression of genes controlling nutrient handling. We evaluate the possibility
      that SIRT1 lies at the heart of a regulatory loop involving PPARalpha, PGC-1alpha
      (PPARA, PPARGC1A as given in the HUGO Database), and lipin-1 (LPIN1 as listed in
      the HUGO Database) that ultimately controls the metabolic response to varying
      nutrient and physiological signals via a common mechanism mediated by post
      translation modifications (deacetylation) of both PPARalpha and PGC-1s. Finally,
      we comment on the potential of pharmaceutical manipulation of these targets as
      well as the possible problems associated with this strategy.

PMID- 19770179
TI  - Improving the pharmacokinetics/pharmacodynamics of prolactin, GH, and their
      antagonists by fusion to a synthetic albumin-binding peptide.
AB  - To prolong the circulation half-life of human prolactin (hPRL), human GH (hGH),
      and their competitive antagonists, hPRL-G129R and hGH-G120R, we examined the
      effects of fusing a serum albumin-binding peptide (SA20) to their amino- or
      carboxyl-terminus. Fusion of the SA20 peptide to the amino-terminus of the
      ligands was less detrimental upon their ability to induce or inhibit signal
      transduction and cell proliferation in vitro than fusion to the carboxyl
      terminus. Pharmacokinetic (PK) studies in mice revealed that the half-life of
      SA20-hPRL and SA20-hGH was prolonged and their clearance was reduced in
      comparison with hPRL and hGH. Pharmacodynamic (PD) studies in 8-week-old female
      mice revealed that lobuloalveolar development in mammary glands was greater in
      all three groups (daily, every 2 days, or every third day over a 12-day period)
      of mice treated with SA20-hPRL (4 mg/kg) compared with hPRL (3.59 mg/kg).
      Similarly, daily administration (i.p.) of SA20-hGH (8 mg/kg) or hGH (7.15 mg/kg)
      to 23-day-old female mice over a 40-day period revealed the superiority of SA20
      hGH over hGH as measured by weight gain, body length, and lobuloalveolar
      development in the mammary glands. These findings indicate that SA20 modification
      of hPRL, hGH, and their respective antagonists improves their PK/PD properties.

PMID- 19770178
TI  - Current views on type 2 diabetes.
AB  - Type 2 diabetes mellitus (T2DM) affects a large population worldwide. T2DM is a
      complex heterogeneous group of metabolic disorders including hyperglycemia and
      impaired insulin action and/or insulin secretion. T2DM causes dysfunctions in
      multiple organs or tissues. Current theories of T2DM include a defect in insulin
      mediated glucose uptake in muscle, a dysfunction of the pancreatic beta-cells, a
      disruption of secretory function of adipocytes, and an impaired insulin action in
      liver. The etiology of human T2DM is multifactorial, with genetic background and
      physical inactivity as two critical components. The pathogenesis of T2DM is not
      fully understood. Animal models of T2DM have been proved to be useful to study
      the pathogenesis of, and to find a new therapy for, the disease. Although
      different animal models share similar characteristics, each mimics a specific
      aspect of genetic, endocrine, metabolic, and morphologic changes that occur in
      human T2DM. The purpose of this review is to provide the recent progress and
      current theories in T2DM and to summarize animal models for studying the
      pathogenesis of the disease.

PMID- 19770180
TI  - Screening for intracranial aneurysms in ADPKD.

PMID- 19770186
TI  - Hormone and glucose signalling in POMC and AgRP neurons.
AB  - In the wake of the obesity pandemic, increased research efforts are under way to
      define how peripheral hormones and metabolites regulate energy homeostasis. The
      melanocortin system, comprising anorexigenic proopiomelanocortin (POMC)
      expressing neurons and orexigenic agouti-related protein (AgRP)/neuropeptide Y
      (NPY) coexpressing neurons in the arcuate nucleus of the hypothalamus are crucial
      for normal energy homeostasis both in rodents and humans. They are regulated by
      peripheral hormones such as leptin and insulin, as well as nutrients such as
      glucose, amino acids and fatty acids. Although much progress has been made,
      recent reports continue to underline how restricted our understanding of POMC and
      AgRP/NPY neuron regulation by these signals is. Importantly, ATP-dependent
      potassium (K(ATP)) channels are regulated both by ATP (from glucose metabolism)
      and by leptin and insulin, and directly control electrical excitability of both
      POMC and AgRP neurons. Thus, this review attempts to offer an integrative
      overview about how peripheral signals, particularly leptin, insulin and glucose,
      converge on a molecular level in POMC and AgRP neurons of the arcuate nucleus of
      the hypothalamus to control energy homeostasis.

PMID- 19770187
TI  - Frequency-dependent disynaptic inhibition in the pyramidal network: a ubiquitous
      pathway in the developing rat neocortex.
AB  - The general structure of the mammalian neocortex is remarkably similar across
      different cortical areas. Despite certain cytoarchitectural specializations and
      deviations from the general blueprint, the principal organization of the
      neocortex is relatively uniform. It is not known, however, to what extent
      stereotypic synaptic pathways resemble each other between cortical areas, and how
      far they might reflect possible functional uniformity or specialization. Here, we
      show that frequency-dependent disynaptic inhibition (FDDI) is a generic circuit
      motif that is present in all neocortical areas we investigated (primary
      somatosensory, auditory and motor cortex, secondary visual cortex and medial
      prefrontal cortex of the developing rat). We did find, however, area-specific
      differences in occurrence and kinetics of FDDI and the short-term dynamics of
      monosynaptic connections between pyramidal cells (PCs). Connectivity between PCs,
      both monosynaptic and via FDDI, is higher in primary cortices. The long-term
      effectiveness of FDDI is likely to be limited by an activity-dependent
      attenuation of the PC-interneuron synaptic transmission. Our results suggest that
      the basic construction of neocortical synaptic pathways follows principles that
      are independent of modality or hierarchical order within the neocortex.

PMID- 19770188
TI  - Orthostatic stress, haemorrhage and a bankrupt cardiovascular system.

PMID- 19770189
TI  - Caffeine in the neonatal period induces long-lasting changes in sleep and
      breathing in adult rats.
AB  - Caffeine is commonly used clinically to treat apnoeas and unstable breathing
      associated with premature birth. Caffeine antagonizes adenosine receptors and
      acts as an efficient respiratory stimulant in neonates. Owing to its persistent
      effects on adenosine receptor expression in the brain, neonatal caffeine
      administration also has significant effects on maturation of the respiratory
      control system. However, since adenosine receptors are critically involved in
      sleep regulation, and sleep also modulates breathing, we tested the hypothesis
      that neonatal caffeine treatment disrupts regulation of sleep and breathing in
      the adult rat. Neonatal caffeine treatment (15 mg kg(-1) day(-1)) was
      administered from postnatal days 3-12. At adulthood (8-10 weeks old), sleep and
      breathing were measured with a telemetry system and whole-body plethysmography
      respectively. In adult rats treated with caffeine during the neonatal period,
      sleep time was reduced, sleep onset latency was increased, and non-rapid eye
      movement (non-REM) sleep was fragmented compared to controls. Ventilation at rest
      was higher in caffeine-treated adult rats compared to controls across sleep/wake
      states. Hypercapnic ventilatory responses were significantly reduced in caffeine
      treated rats compared to control rats across sleep/wake states. Additional
      experiments in adult anaesthetized rats showed that at similar levels of arterial
      blood gases, phrenic nerve activity was enhanced in caffeine-treated rats. This
      study demonstrates that administration of caffeine in the neonatal period alters
      respiratory control system activity in awake and sleeping rats, as well as in the
      anaesthetized rats, and also has persistent disrupting effects on sleep that are
      apparent in adult rats.

PMID- 19770190
TI  - Activation of native TRPC1/C5/C6 channels by endothelin-1 is mediated by both
      PIP3 and PIP2 in rabbit coronary artery myocytes.
AB  - We investigate activation mechanisms of native TRPC1/C5/C6 channels (termed TRPC1
      channels) by stimulation of endothelin-1 (ET-1) receptor subtypes in freshly
      dispersed rabbit coronary artery myocytes using single channel recording and
      immunoprecipitation techniques. ET-1 evoked non-selective cation channel currents
      with a unitary conductance of 2.6 pS which were not inhibited by either ET(A) or
      ET(B) receptor antagonists, respectively BQ-123 and BQ788, when administered
      separately. However, in the presence of both antagonists, ET-1-evoked channel
      activity was abolished indicating that both ET(A) and ET(B) receptor stimulation
      activate this conductance. Stimulation of both ET(A) and ET(B) receptors evoked
      channel activity which was inhibited by the protein kinase C (PKC) inhibitor
      chelerythrine and by anti-TRPC1 antibodies indicating that activation of both
      receptor subtypes causes TRPC1 channel activation by a PKC-dependent mechanism.
      ET(A) receptor-mediated TRPC1 channel activity was selectively inhibited by
      phosphoinositol-3-kinase (PI-3-kinase) inhibitors wortmannin (50 nM) and PI-828
      and by antibodies raised against phosphoinositol-3,4,5-trisphosphate (PIP(3)),
      the product of PI-3-kinase-mediated phosphorylation of phosphatidylinositol 4,5
      bisphosphate (PIP(2)). Moreover, exogenous application of diC8-PIP(3) stimulated
      PKC-dependent TRPC1 channel activity. These results indicate that stimulation of
      ET(A) receptors evokes PKC-dependent TRPC1 channel activity through activation of
      PI-3-kinase and generation of PIP(3). In contrast, ET(B) receptor-mediated TRPC1
      channel activity was inhibited by the PI-phospholipase C (PI-PLC) inhibitor
      U73122. 1-Oleoyl-2-acetyl-sn-glycerol (OAG), an analogue of diacylglycerol (DAG),
      which is a product of PI-PLC, also activated PKC-dependent TRPC1 channel
      activity. OAG-induced TRPC1 channel activity was inhibited by anti
      phosphoinositol-4,5-bisphosphate (PIP(2)) antibodies and high concentrations of
      wortmannin (20 microM) which depleted tissue PIP(2) levels. In addition exogenous
      application of diC8-PIP(2) activated PKC-dependent TRPC1 channel activity. These
      data indicate that stimulation of ET(B) receptors evokes PKC-dependent TRPC1
      activity through PI-PLC-mediated generation of DAG and requires a permissive role
      of PIP(2). In conclusion, we provide the first evidence that stimulation of ET(A)
      and ET(B) receptors activate native PKC-dependent TRPC1 channels through two
      distinct phospholipids pathways involving a novel action of PIP(3), in addition
      to PIP(2), in rabbit coronary artery myocytes.

PMID- 19770191
TI  - Hypoxia reduces the hypothalamic thermogenic threshold and thermosensitivity.
AB  - Hypoxia is well known to reduce the body temperature (T(b)) of mammals, although
      the neural origins of this response remain uncertain. Short-term hypoxic exposure
      causes a reduction in the lower critical temperature of the thermal neutral zone
      and a reduction in whole body thermal conductance of rodents, providing indirect
      support that hypoxia lowers T(b) in a regulated manner. In this study, we
      examined directly the potential for changes in central thermosensitivity to evoke
      the hypoxic metabolic response by heating and cooling the preoptic area of the
      hypothalamus (the area which integrates thermoreceptor input and regulates
      thermoeffector outputs) using chronic, indwelling thermodes in ground squirrels
      during normoxia and hypoxia (7, 10 and 12% O(2)). We found that the threshold
      hypothalamic temperature for the metabolic response to cooling (T(th)) of
      approximately 38 degrees C in normoxia was proportionately reduced in hypoxia
      (down to 28-31 degrees C at 7% O(2)) and that the metabolic thermosensitivity
      (alpha; the change in metabolic rate for any given change in hypothalamic
      temperature below the lower critical temperature) was comparatively reduced by 5
      to 9 times. This provides strong support for the hypothesis that the fall in
      temperature that occurs during hypoxia is the result of a reduction in the
      activation of thermogenic mechanisms. The decrease in the central
      thermosensitivity in hypoxia, however, appears to be a critical factor in the
      alteration of mammalian T(b). We suggest, therefore, that an altered central
      thermosensitivity may provide a proximate explanation of how low oxygen and
      similar stressors reduce normal fluctuations in T(b) (i.e. circadian), in
      addition to the depression in regulated T(b).

PMID- 19770192
TI  - What single-channel analysis tells us of the activation mechanism of ligand-gated
      channels: the case of the glycine receptor.
AB  - Glycine receptors are, in several ways, the member of the nicotinic superfamily
      that is best-suited for single-channel recording. That means that they are ideal
      for testing ideas about how activation proceeds in a ligand-gated ion channel
      from the binding of the agonist to the opening of the channel. This review
      describes the quantitative characterization by single-channel analysis of a novel
      activation mechanism for the glycine receptor. The favourable properties of the
      glycine receptor allowed the first detection of a conformation change that
      follows the binding of the agonist but precedes the opening of the channel. We
      used the term 'flipping' to describe this pre-opening conformational change. The
      'flipped' state has a binding affinity higher than the resting state, but lower
      than the open state. This increased affinity presumably reflects a structural
      change near the agonist binding site, possibly the 'capping' of the C-loop. The
      significance of the 'flip' activation mechanism goes beyond understanding the
      behaviour and the structure-function relation of glycine channels, as this
      mechanism can be applied also to other members of the superfamily, such as the
      muscle nicotinic receptor. The 'flip' mechanism has thrown light on the question
      of why partial agonists are not efficacious at keeping the channel open, a
      question that is fundamental to rational drug design. In both muscle nicotinic
      and glycine receptors, partial agonists are as good as full agonists at opening
      the channel once flipping has occurred, but are not as effective as full agonists
      in eliciting this early conformational change.

PMID- 19770194
TI  - Involvement of Na+/Ca2+ exchanger in migration and contraction of rat cultured
      tendon fibroblasts.
AB  - In response to injury and inflammation of tendons, tendon fibroblasts are
      activated, migrate to the wound, and eventually induce contraction of the
      extracellular matrices to repair the tissue. Under such conditions, Ca(2+)
      signalling is involved in motility and contractility of tendon fibroblasts. Using
      cultured tendon fibroblasts isolated from rat Achilles tendons, we investigated
      functional expression of Na(+)/Ca(2+) exchangers (NCX). The fluorometric study
      showed that the intracellular Ca(2+) concentration ([Ca(2+)](i)) was increased by
      reducing extracellular Na(+) concentration ([Na(+)](o)) in tendon fibroblasts.
      Selective NCX inhibitors, KB-R7943 and SEA0400, both attenuated [Na(+)](o)
      dependent [Ca(2+)](i) elevation and the resting [Ca(2+)](i) in tendon
      fibroblasts. RT-PCR, Western blots and sequence analyses revealed that NCX1.3 and
      NCX1.7 were expressed in cultured tendon fibroblasts. NCX2 mRNA was undetected.
      NCX3 expression was negligibly low. Immunofluorescence microscopy indicated that
      NCX1 protein localized in the plasma membrane especially at the microspikes of
      tendon fibroblasts. In the wound-healing scratch assay, the cells migrated toward
      the space created by a scratch and almost completely filled the space within 48
      h. This phenomenon was significantly suppressed by KB-R7943 and SEA0400.
      Furthermore, the NCX inhibitors abrogated the tendon fibroblast-mediated collagen
      matrix contractions. Two types of siRNAs for NCX1 also suppressed the migration
      and contraction of tendon fibroblasts. We conclude that NCX is expressed and
      mediates Ca(2+) influx in cultured tendon fibroblasts. Since the pharmacological
      inhibitors and siRNA for NCX1 suppressed motility and contractility of tendon
      fibroblasts, NCX may play an important role in the function of tendon fibroblasts
      in the wound healing.

PMID- 19770196
TI  - The RE-LY study: Randomized Evaluation of Long-term anticoagulant therapY:
      dabigatran vs. warfarin.

PMID- 19770195
TI  - Modulation of interhemispheric inhibition by volitional motor activity: an
      ipsilateral silent period study.
AB  - Brief interruption of voluntary EMG in a hand muscle by focal transcranial
      magnetic stimulation (TMS) of the ipsilateral primary motor cortex (M1), the so
      called ipsilateral silent period (ISP), is a measure of interhemispheric motor
      inhibition. However, little is known about how volitional motor activity would
      modulate the ISP. Here we tested in 30 healthy adults to what extent and under
      what conditions voluntary activation of the stimulated right M1 by moving the
      left hand strengthens interhemispheric inhibition as indexed by an enhancement of
      the ISP area in the maximally contracting right first dorsal interosseous (FDI).
      Left index finger abduction, already at low levels of contraction, significantly
      enhanced the ISP compared to left hand at rest. Even imagination of left index
      finger movement enhanced the ISP compared to rest or mental calculation. This
      enhancement occurred in the absence of motor-evoked potential amplitude
      modulation in the left FDI, thus excluding a non-specific contribution from an
      increase in right M1 corticospinal excitability. Contraction of the left extensor
      indicis, but not contraction of more proximal left upper limb or left or right
      lower limb muscles also enhanced the ISP. A reaction time experiment showed that
      the ISP enhancement developed at a late stage of movement preparation just before
      or at movement onset. Interhemispheric inhibition of the motor-evoked potential
      as tested by a bifocal paired-pulse TMS protocol and thought to be mediated via a
      neuronal circuit different to the ISP was not enhanced when tested under
      identical motor task conditions. Finally, ISP enhancement by contraction of the
      left FDI correlated inversely with EMG mirror activity in the right FDI during
      phasic abductions of the left index finger. Our findings strongly suggest that
      voluntary M1 activation by real or imagined movement of the contralateral hand
      increases interhemispheric motor inhibition of the opposite M1. This phenomenon
      shows substantial topographical, temporal and neuronal circuit specificity, and
      has functional significance as it probably plays a pivotal role in suppressing
      mirror activity.

PMID- 19770197
TI  - Effects of early childhood lead exposure on academic performance and behaviour of
      school age children.
AB  - AIM: To determine whether early lead exposure at levels below 10 microg/dl has an
      impact on educational and behavioural outcomes at school. METHODS: Venous samples
      were taken from a subgroup of the Avon Longitudinal Study of Parents and Children
      (ALSPAC) attending a research clinic at 30 months of age (n = 582), and lead
      levels were measured by atomic absorption spectrometry. Developmental,
      behavioural and standardised educational outcomes (Standard Assessment Tests,
      SATs) were collected on these children at age 7-8 years. In the analysis, blood
      lead concentration was investigated both as a continuous covariate and as a
      categorical variable. RESULTS: 488 cases (84%) had complete data on confounders
      and outcomes. After adjustment for confounders and using a log dose-response
      model for lead concentration, blood lead levels showed significant associations
      with reading, writing and spelling grades on SATs, and antisocial behaviour. A
      doubling in lead concentration was associated with a 0.3 point (95% CI -0.5 to 
      0.1) decline in SATs grades. Treating lead levels categorically, with the
      reference group 0-2 microg/dl, no effects on outcomes were apparent at 2-5
      microg/dl, but levels of 5-10 microg/dl were associated with a reduction in
      scores for reading (OR 0.51, p = 0.006) and writing (OR 0.49, p = 0.003). Lead
      levels >10 microg/dl were also associated with increased scores for antisocial
      behaviour (OR 2.9, p = 0.040) and hyperactivity (OR 2.82, p = 0.034).
      CONCLUSIONS: Exposure to lead early in childhood has effects on subsequent
      educational attainment, even at blood levels below 10 microg/dl. These data
      suggest that the threshold for clinical concern should be reduced to 5 microg/dl.

PMID- 19770200
TI  - CT images of Hirschsprung's associated enterocolitis: a rare finding.

PMID- 19770204
TI  - Pervasive transcription of the eukaryotic genome: functional indices and
      conceptual implications.
AB  - Genome-wide analyses of the eukaryotic transcriptome have revealed that the
      majority of the genome is transcribed, producing large numbers of non-protein
      coding RNAs (ncRNAs). This surprising observation challenges many assumptions
      about the genetic programming of higher organisms and how information is stored
      and organized within the genome. Moreover, the rapid advances in genomics have
      given little opportunity for biologists to integrate these emerging findings into
      their intellectual and experimental frameworks. This problem has been compounded
      by the perception that genome-wide studies often generate more questions than
      answers, which in turn has led to confusion and controversy. In this article, we
      address common questions associated with the phenomenon of pervasive
      transcription and consider the indices that can be used to evaluate the function
      (or lack thereof) of the resulting ncRNAs. We suggest that many lines of
      evidence, including expression profiles, conservation signatures, chromatin
      modification patterns and examination of increasing numbers of individual cases,
      argue in favour of the widespread functionality of non-coding transcription. We
      also discuss how informatic and experimental approaches used to analyse protein
      coding genes may not be applicable to ncRNAs and how the general perception that
      protein-coding genes form the main informational output of the genome has
      resulted in much of the misunderstanding surrounding pervasive transcription and
      its potential significance. Finally, we present the conceptual implications of
      the majority of the eukaryotic genome being functional and describe how
      appreciating this perspective will provide considerable opportunity to further
      understand the molecular basis of development and complex diseases.

PMID- 19770205
TI  - Why castration-resistant prostate cancer patients with neuroendocrine
      differentiation should be addressed to a cisplatin-based regimen.

PMID- 19770206
TI  - Immature rat seminiferous tubules reconstructed in vitro express markers of
      Sertoli cell maturation after xenografting into nude mouse hosts.
AB  - Sertoli cells undergo a maturation process during post-natal testicular
      development that leads to the adult-type Sertoli cell, which is required for
      spermatogenesis. Understanding Sertoli cell maturation is therefore necessary to
      gain insight into the underlying causes of impaired spermatogenesis and male
      infertility. The present study characterized the cellular and molecular
      differentiation of Sertoli cells in a xenograft model of mammalian testicular
      development. Immature rat Sertoli cells were cultured in a three-dimensional
      culture system to allow the formation of cord-like structures. The in vitro
      Sertoli cell cultures were then grafted into nude mice. Sertoli cell
      proliferation, morphological differentiation and mRNA expression of Sertoli cell
      maturation markers were evaluated in xenografts. Sertoli cell proliferation
      significantly decreased between 1 and 4 weeks (6.7 +/- 0.9 versus 1.2+/- 0.1%, P
      < 0.001), and was maintained at low levels thereafter. Sertoli cell cord-like
      structures significantly decreased between 1 and 4 weeks (59.6 versus 21%, P <
      0.05), whereas Sertoli cell tubules were more frequently observed after 4 weeks
      (13.3 versus 73.1%, P < 0.05). Furthermore, expression of androgen binding
      protein, transferrin and follicle stimulating hormone receptor, markers for
      mature Sertoli cells, was detected after 1 week of grafting and increased
      significantly thereafter. We conclude from these results that rat Sertoli cells
      continue maturation after xenografting to the physiological environment of a
      host. This model of in vitro tubule formation will be helpful in future
      investigations addressing testicular maturation in the mammalian testis.

PMID- 19770207
TI  - Evaluation of the implementation of radiation protection measures for aircrew in
      EU member states.
AB  - An evaluation of the implementation of radiation protection measures for aircrew
      in EU Member States has recently been performed in a study sponsored by the
      European Commission. A comprehensive database has been gathered using
      questionnaires for civil aviation authorities, aircraft operators and radiation
      protection authorities in each country. The study has revealed the following
      results: all countries within the scope of this study where aircrew might receive
      annual doses >1 mSv have implemented appropriate legislation. The treatment of
      limits or constraints (action levels) for annual doses of 1, 6, 20 mSv could be
      an area where clear guidance by the European Commission might be needed. The way
      in which doses are determined might also be treated in a more harmonized way in
      the EU, including the transfer of dose data of freelancers or crew members
      working for other airlines. The establishment of the European Aviation Safety
      Agency leads to a gradual shift in responsibilities from the national civil
      aviation authorities towards this centralised European agency. Currently,
      however, tracking of doses for aircrew still lies with national bodies.

PMID- 19770208
TI  - Radiation protection constraints for use of proton and ion accelerators in
      medicine.
AB  - This paper gives some guidelines for radiation protection at proton therapy
      facilities. The energy and angular distribution of secondary radiation from thick
      iron and tissue targets bombarded by 250-MeV protons were calculated with Monte
      Carlo simulations in order to emphasise the influence of the various components
      of the radiation field on the shielding design. The main constraints for
      radiation protection (e.g. workload, use and occupancy factors, etc.), shielding
      design (including access mazes) and the estimate of material activation are also
      discussed with some practical examples.

PMID- 19770209
TI  - Programmes for the evaluation of the environmental impact.
AB  - The article provides an overview of the different components of programmes for
      the evaluation of the environmental impact of accelerator facilities. The
      starting point is the knowledge of radiation and radionuclides that may be
      encountered in the environment of accelerators. The second step is an efficient
      environmental monitoring programme suitable for the given source term. The
      results of the monitoring programme provide an input for models calculating the
      maximum effective dose received by members of the public, so expressing the
      dosimetric impact of the facility.

PMID- 19770210
TI  - Radon concentrations in three underground lignite mines in Turkey.
AB  - Monitoring of radon in underground mines is important in order to assess the
      radiological hazards to occupational workers. Radon concentration levels in three
      underground lignite mines (Tuncbilek, Omerler and Eynez) of Turkey were obtained
      in this study. For this reason, atmospheric radon level measurements were carried
      out in mines using CR-39 track detectors. Chemical etching of the detector tracks
      and subsequent counting were performed at Cekmece Nuclear Research and Training
      Center. The obtained results were evaluated according to the International
      Commission of Radiation Protection and the Turkish Atomic Energy Authority whose
      radon action levels for workplaces are 500-1500 and 1000 Bq(-3), respectively.
      The radon gas concentrations in the lignite mines were determined to be between
      50 +/- 7 and 587 +/- 16 Bq m(-3). The results obtained in these experiments are
      far under the action levels. The computed radon doses for the mine workers of
      Tuncbilek, Omerler and Eynez lignite mines are 1.23, 2.44 and 1.47 mSv y(-1),
      respectively.

PMID- 19770212
TI  - Patient dose assessment due to fluoroscopic exposure for some selected
      fluoroscopic procedures in Ghana.
AB  - Organ and effective doses to 90 patients undergoing some selected fluoroscopic
      examinations at the Korle-Bu Teaching Hospital were estimated using the Monte
      Carlo-based program (PCXMC version 1.5). Radiation dose was estimated from free
      in-air measurements. The mean effective doses were found to be 0.29 +/- 0.07,
      0.84 +/- 0.13, 3.15 +/- 0.44, 6.24 +/- 0.70 and 0.38 +/- 0.05 mSv for
      urethrogram, barium swallow, barium meal, barium enema and myelogram
      examinations, respectively. The dose area product was estimated to be 3.55 +/-
      0.95, 16.44 +/- 2.60, 50.81 +/- 7.04, 99.69 +/- 10.85 and 9.32 +/- 0.99 Gy cm(2)
      for urethrogram, barium swallow, barium meal, barium enema and myelogram
      examinations, respectively. Optimisation of procedures is required for barium
      enema and barium meal examinations.

PMID- 19770213
TI  - Activity and radiation protection studies for the W-Ta target of CSNS.
AB  - The Chinese government initiated a conceptual design for the project of China
      Spallation Neutron Source (CSNS), which consists of an H-linear accelerator, a
      rapid cycling synchrotron accelerating the beam to 1.6 GeV, a target station
      converting proton beam into lower energy (<1 eV) neutron beam optimised to
      instruments for neutron scattering applications. The facility operates at 25-Hz
      repetition rate with an initial beam power of 100 kW. In the target station, the
      target-moderator-reflector (TMR) components are exposed to the intensive fluxes
      of high-energy hadrons and become highly radioactive as a result of long-time
      irradiation. In this paper, the activity of the TMR components are calculated
      using the Monte Carlo code system LAHET&MCNP4C&CINDER'90. Comparisons of some
      results with that simulated by FLUKA code are also performed. Detailed analyses
      of the radionuclides and their characters in the tantalum clad tungsten target (W
      Ta target) are important for the radiation protection of the CSNS target station.
      The shielding design of the service cell for the decay gamma ray induced from the
      W-Ta target and its vessel shows that the ambient dose rate decreases
      exponentially with increasing heavy concrete thickness. And 80 cm thickness of
      heavy concrete for each side of the service cell can satisfy the safety
      requirement.

PMID- 19770214
TI  - Occupational health needs of commercial fishermen in South West England.
AB  - BACKGROUND: Work in commercial fishing is physically demanding and hazardous, but
      unlike merchant seamen, fishermen are not required to hold a certificate of
      medical fitness. AIMS: To investigate the case for regulatory medical standards
      for commercial fishermen and to identify priorities for the prevention and
      management of occupational injuries at sea. METHODS: We surveyed a convenience
      sample of fishermen at three major fishing ports in South West England using a
      standardized interview-administered questionnaire. RESULTS: Interviews were
      completed by 210 (68%) of 307 fishermen approached. Over their careers, 56
      subjects (27%) had been returned to shore as an emergency for medical reasons, a
      rate of 14.6 (95% confidence interval 11.5-18.2) per 1000 man-years. Most
      emergency evacuations were for acute injuries, and only five were for illness. A
      few participants suffered from chronic disease that would call into question
      their fitness to go to sea. Fifty-five fishermen had suffered injuries in the
      past 12 months, including 12 that had caused loss of more than 3 days from work.
      Subjects had self-stitched 4 of 15 reported hand lacerations, while others had
      been bound with 'gaffer' tape. CONCLUSIONS: Prevention of hand lacerations should
      be a high priority, with first-aid training and equipment for fishing crews to
      improve their care when prevention fails. No firm conclusions can be drawn about
      the value of regular medical screening for commercial fishermen, but such
      screening should be considered a lower priority than accident prevention.

PMID- 19770215
TI  - Plant terpenes affect intensity and temporal parameters of pheromone detection in
      a moth.
AB  - In moths, the components of the female pheromone blend are detected in the male
      antennae by pheromone olfactory receptor neurons (Ph-ORNs) expressing narrowly
      tuned olfactory receptors. Responses to sex pheromones have generally been
      thought to be independent from the odorant background. However, interactions
      between pheromone components and plant volatiles have been reported at behavioral
      and detection levels. To document the mechanisms of such interactions, we
      analyzed Ph-ORN responses of Spodoptera littoralis to the main pheromone
      component, Z9E11-14:Ac, in the presence of 4 monoterpenes. To mimic natural
      contexts in which plant odors and pheromone emanate from different sources, the 2
      stimuli were presented with different temporal patterns and from independent
      sources. Linalool reversibly reduced the firing response to Z9E11-14:Ac and
      produced an off effect. Geraniol and geranyl and linalyl acetates reduced the
      responses to Z9E11-14:Ac with a longer time course. Pulses of linalool over
      prolonged pheromone stimulation resulted in a discontinuous firing activity.
      Pulses of pheromone were better separated over a background of linalool, compared
      with odorless air. The data confirm that plant compounds may modulate the
      intensity and the temporal coding by Ph-ORNs of pheromone information. This
      modulation might positively affect mate location at high pheromone density
      especially nearby a pheromone source.

PMID- 19770216
TI  - Local and remote epileptogenicity in focal cortical dysplasias and
      neurodevelopmental tumours.
AB  - During the pre-surgical evaluation of drug-resistant epilepsy, the assessment of
      the extent of the epileptogenic zone and its organization is a crucial objective.
      Indeed, the epileptogenic zone may be organized as a simple focal lesional site
      or as a more complex network (often referred to as the 'epileptogenic network')
      extending beyond the lesion. This distinction is particularly relevant in
      developmental lesions such as focal cortical dysplasias or dysembryoplastic
      neuroepithelial tumours and may determine both the surgical strategy and the
      prognosis. In this study, we have quantified the epileptogenic characteristic of
      brain structures explored by depth electrodes in 36 patients investigated by
      stereoelectroencephalography and suffering from focal drug-resistant epilepsy
      associated with focal cortical dysplasias or dysembryoplastic neuroepithelial
      tumours. This quantification was performed using the 'Epileptogenicity Index'
      method that accounts for both the propensity of a brain area to generate rapid
      discharges and the time for this area to get involved in the seizure.
      Epileptogenicity Index values range from 0 (no epileptogenicity) to 1 (maximal
      epileptogenicity). We determined Epileptogenicity Index from signals recorded in
      distinct brain structures including the lesional site. We studied the type of
      epileptogenic zone organization (focal versus network) and looked for a
      correlation with clinical data and post-surgical outcome. Mean Epileptogenicity
      Index in lesional regions was 0.87 (+/-0.25), and 0.29 (+/-0.30) in 'non
      lesional' structures. The number of highly epileptogenic structures (defined by
      Epileptogenicity Index value >or=0.4) was 3.14 (+/-1.87) in the whole population.
      We found that 31% of patients had only one epileptogenic structure (N(EI>or=0.4)
      = 1), therefore disclosing a strictly focal epileptogenic zone organization while
      25 patients had more than one epileptogenic region, disclosing a network (61%) or
      bilateral (8%) epileptogenic zone organization. We observed a trend for a
      difference in seizure outcome according to the type of epileptogenic zone
      organization. Indeed, 57% of patients with network organization and 87% with
      focal organization were seizure-free while none of those with bilateral
      organization became seizure-free. The determination of Epileptogenicity Index
      computed from electrophysiological signals recorded according to the
      stereoelectroencephalography technique is a novel tool. Results suggest that it
      can help in the delineation of the epileptogenic zone associated with brain
      lesions and that it could be used in the definition of the subsequent surgical
      resection.

PMID- 19770217
TI  - 'Audit' papers.

PMID- 19770218
TI  - Lonely patients in general practice: a call for revealing GPs' emotions? A
      qualitative study.
AB  - BACKGROUND: Loneliness is a universal phenomenon that influences one's health and
      health perception. GPs are confronted with lonely people quite often. Yet, what
      GPs think of this phenomenon and how they deal with emotions lonely patients
      evoke is not known. OBJECTIVE: We aimed to explore GPs' experiences with lonely
      patients. We wanted to gain insight in GPs' feelings regarding consultations with
      lonely patients and potential resulting behaviour from these feelings. METHODS:
      We performed a qualitative study based on semi-structured interviews. We
      interviewed 20 Dutch GPs. Transcripts were analysed according to a grounded
      theory-like method in order to bring to surface key concepts and relations
      between them. RESULTS: GPs considered loneliness as something subjective, a
      feeling. They found it relevant to know whether their patients were lonely.
      However, they had difficulty defining their task and experienced a lack of
      therapeutic options. Beside feelings of pity and interest, lonely patients could
      evoke feelings of frustration and powerlessness. These feelings were more
      pronounced when patients were chronically lonely and could cause GPs to spend
      less time on these patients or refer them more often. GPs did not constructively
      use their own emotions during consultation. CONCLUSIONS: When confronted with
      lonely patients, a helpful distinction could be made between transitory and
      chronic loneliness. Chronically lonely patients are more likely to evoke negative
      feelings and behaviour in their GPs. GPs should try to recognize these emotions
      and make sure they do not harmfully influence consultation.

PMID- 19770219
TI  - Young women and their reproductive health needs in a family practice setting:
      factors influencing care seeking in Vitoria, Brazil.
AB  - BACKGROUND: Young women often have diverse options for addressing their
      reproductive health and other health needs in urban settings. In Brazil, they may
      access care through the government-run Family Health Program (FHP). Understanding
      factors associated with service utilization can enhance access to and delivery of
      appropriate services. OBJECTIVES: To describe demographic, behavioural and
      clinical characteristics of young women accessing services through FHP in
      Vitoria, Brazil. METHODS: From March to December 2006, women aged 18-29 years
      were recruited into a population-based, household survey. Responses were analysed
      to assess previous 6 months utilization of FHP services in this population and
      characteristics associated with accessing care through this public family
      practice model. RESULTS: Of 1200 eligible women identified, 1029 enrolled
      (85.7%). Median age was 23 (interquartile range 20-26) years, 42.7% were married
      or cohabitating with a male partner. A majority (72%) accessed FHP services in
      the preceding 6 months, principally for routine and gynaecological visits.
      Factors independently associated with seeking FHP included: ever tested for human
      immunodeficiency virus, using anal sex as contraceptive method and reporting a
      current vaginal discharge. Prior commercial sex work, previous diagnosis with an
      sexually transmitted infection or using oral sex as a contraceptive method were
      associated with less use of FHP services. CONCLUSIONS: A public option for
      delivery of FHP has attracted wide utilization across a cross-section of young
      women in Vitoria, Brazil. Greater sensitization to specific practices and needs
      of this population, especially around reproductive health, could further enhance
      the services provided by family practitioners.

PMID- 19770220
TI  - Developmental effects of aggressive behavior in male adolescents assessed with
      structural and functional brain imaging.
AB  - Aggressive behavior is common during adolescence. Although aggression-related
      functional changes in the ventromedial prefrontal cortex (vmPFC) and frontopolar
      cortex (FPC) have been reported in adults, the neural correlates of aggressive
      behavior in adolescents, particularly in the context of structural
      neurodevelopment, are obscure. We used functional and structural magnetic
      resonance imaging (MRI) to measure the blood oxygenation level-depended signal
      and cortical thickness. In a block-designed experiment, 14-17-year old
      adolescents imagined aggressive and non-aggressive interactions with a peer. We
      show reduced vmPFC activation associated with imagined aggressive behavior as
      well as enhanced aggression-related activation and cortical thinning in the FPC
      with increasing age. Changes in FPC activation were also associated with
      judgments of the severity of aggressive acts. Reduced vmPFC activation was
      associated with greater aggression indicating its normal function is to exert
      inhibitory control over aggressive impulses. Concurrent FPC activation likely
      reflects foresight of harmful consequences that result from aggressive acts. The
      correlation of age-dependent activation changes and cortical thinning
      demonstrates ongoing maturation of the FPC during adolescence towards a
      refinement of social and cognitive information processing that can potentially
      facilitate mature social behavior in aggressive contexts.

PMID- 19770223
TI  - Novel internal regions of fluorescent proteins undergo divergent evolutionary
      patterns.
AB  - Over the past decade, fluorescent proteins (FPs) have become ubiquitous tools in
      biological research. Yet, little is known about the natural function or evolution
      of this superfamily of proteins that originate from marine organisms. Using
      molecular phylogenetic analyses of 102 naturally occurring cyan fluorescent
      proteins, green fluorescent proteins, red fluorescent proteins, as well as the
      nonfluorescent (purple-blue) protein sequences (including new FPs from Lizard
      Island, Australia) derived from organisms with known geographic origin, we show
      that FPs consist of two distinct and novel regions that have evolved under
      opposite and sharply divergent evolutionary pressures. A central region is highly
      conserved, and although it contains the residues that form the chromophore, its
      evolution does not track with fluorescent color and evolves independently from
      the rest of the protein. By contrast, the regions enclosing this central region
      are under strong positive selection pressure to vary its sequence and yet
      segregate well with fluorescence color emission. We did not find a significant
      correlation between geographic location of the organism from which the FP was
      isolated and molecular evolution of the protein. These results define for the
      first time two distinct regions based on evolution for this highly compact
      protein. The findings have implications for more sophisticated bioengineering of
      this molecule as well as studies directed toward understanding the natural
      function of FPs.

PMID- 19770224
TI  - Effects of reproductive stage, GH, and 11-ketotestosterone on expression of
      growth differentiation factor-9 in the ovary of the eel, Anguilla australis.
AB  - In order to study the regulation of the growth differentiation factor-9 (gdf9)
      gene in a primitive teleost with semelparous life history, we cloned a cDNA
      encoding shortfinned eel Gdf9, expressed a partial peptide in Escherichia coli,
      and raised an antiserum to evaluate changes in Gdf9 expression during its
      pituitary homogenate-induced reproductive cycle. The effects of in vivo and in
      vitro exposure to the androgen 11-ketotestosterone (11-KT), known to affect
      previtellogenic (PV) oocyte growth, were also determined. Furthermore, we
      investigated whether Gdf9 expression was metabolically gated by treating PV fish
      with recombinant GH in vivo. Immunoreactive proteins of ca. 52 and 55 kDa were
      identified by western blot analysis. Gdf9 message and protein were most abundant
      in PV oocytes, and peaked slightly earlier for mRNA than for protein. Captivity
      resulted in reduced gdf9 mRNA levels, which were restored following pituitary
      homogenate treatment. As oocytes progressed through induced oogenesis, Gdf9
      expression decreased. Neither 11-KT nor GH treatment affected gdf9 mRNA levels in
      PV fish, although GH could partially restore handling- or captivity-induced
      decreases in gdf9 mRNA levels. Semelparous eels thus show an expression pattern
      of Gdf9 during oogenesis that is similar to that seen in other vertebrates, that
      appears responsive to handling or captivity stress, and whose control remains to
      be elucidated.

PMID- 19770226
TI  - Health inequalities in European welfare states.

PMID- 19770227
TI  - Human ecology and public health.

PMID- 19770225
TI  - Differential activation of mitochondrial apoptotic pathways by vasculotropic
      amyloid-beta variants in cells composing the cerebral vessel walls.
AB  - Cerebral amyloid angiopathy (CAA) is an age-associated condition and a common
      finding in Alzheimer's disease in which amyloid-beta (Abeta) vascular deposits
      are featured in >80% of the cases. Familial Abeta variants bearing substitutions
      at positions 21-23 are primarily associated with CAA, although they manifest with
      strikingly different clinical phenotypes: cerebral hemorrhage or dementia. The
      recently reported Piedmont L34V Abeta mutant, located outside the hot spot 21-23,
      shows a similar hemorrhagic phenotype, albeit less aggressive than the widely
      studied Dutch E22Q variant. We monitored the apoptotic events occurring after
      stimulation of human brain microvascular endothelial and smooth muscle cells with
      nonfibrillar structures of both variants and wild-type Abeta40. Induction of
      analogous caspase-mediated mitochondrial pathways was elicited by all peptides,
      although within different time frames and intensity. Activated pathways were
      susceptible to pharmacological modulation either through direct inhibition of
      mitochondrial cytochrome c release or by the action of pan- and pathway-specific
      caspase inhibitors, giving a clear indication of the independent or synergistic
      engagement of both extrinsic and intrinsic mechanisms. Structural analyses of the
      Abeta peptides showed that apoptosis preceded fibril formation, correlating with
      the presence of oligomers and/or protofibrils. The data support the notion that
      rare genetic mutations constitute unique paradigms to understand the molecular
      pathogenesis of CAA.

PMID- 19770222
TI  - Zebu cattle are an exclusive legacy of the South Asia neolithic.
AB  - Animal domestication was a major step forward in human prehistory, contributing
      to the emergence of more complex societies. At the time of the Neolithic
      transition, zebu cattle (Bos indicus) were probably the most abundant and
      important domestic livestock species in Southern Asia. Although archaeological
      evidence points toward the domestication of zebu cattle within the Indian
      subcontinent, the exact geographic origins and phylogenetic history of zebu
      cattle remains uncertain. Here, we report evidence from 844 zebu mitochondrial
      DNA (mtDNA) sequences surveyed from 19 Asiatic countries comprising 8 regional
      groups, which identify 2 distinct mitochondrial haplogroups, termed I1 and I2.
      The marked increase in nucleotide diversity (P < 0.001) for both the I1 and I2
      haplogroups within the northern part of the Indian subcontinent is consistent
      with an origin for all domestic zebu in this area. For haplogroup I1, genetic
      diversity was highest within the Indus Valley among the three hypothesized
      domestication centers (Indus Valley, Ganges, and South India). These data support
      the Indus Valley as the most likely center of origin for the I1 haplogroup and a
      primary center of zebu domestication. However, for the I2 haplogroup, a complex
      pattern of diversity is detected, preventing the unambiguous pinpointing of the
      exact place of origin for this zebu maternal lineage. Our findings are discussed
      with respect to the archaeological record for zebu domestication within the
      Indian subcontinent.

PMID- 19770228
TI  - Privatization processes in health care in Europe--a move in the right direction,
      a 'trendy' option, or a step back?

PMID- 19770229
TI  - The role of the private sector in health financing and service delivery.

PMID- 19770230
TI  - Imitation in fragile X syndrome. Implications for autism.
AB  - To address the specific impairment of imitation in autism, the imitation
      abilities of 22 children with fragile X syndrome (FXS) with and without autism
      were compared. Based on previous research, we predicted that children with FXS
      and autism would have significantly more difficulty with non-meaningful imitation
      tasks. After controlling for full-scale IQ and age, the groups did not differ in
      their overall imitation accuracy scores, but analysis of error patterns revealed
      that children with FXS and autism made more groping errors and additional
      movements than the comparison group. These error patterns are consistent with the
      hypothesis that an action production system deficit plays an important role in
      the overall imitation deficit in autism, at least in children with FXS.

PMID- 19770231
TI  - Attentional blink in young people with high-functioning autism and Asperger's
      disorder.
AB  - The aim of the study was to examine the temporal characteristics of information
      processing in individuals with high-functioning autism and Asperger's disorder
      using a rapid serial visual presentation paradigm. The results clearly showed
      that such people demonstrate an attentional blink of similar magnitude to
      comparison groups. This supports the proposition that the social processing
      difficulties experienced by these individuals are not underpinned by a basic
      temporal-cognitive processing deficit, which is consistent with Minshew's complex
      information processing theory. This is the second study to show that automatic
      inhibitory processes are intact in both autism and Asperger's disorder, which
      appears to distinguish these disorders from some other frontostriatal disorders.
      The finding that individuals with autism were generally poorer than the
      comparison group at detecting black Xs, while being as good in responding to
      white letters, was accounted for in the context of a potential dual-task
      processing difficulty or visual search superiority.

PMID- 19770232
TI  - The Global Tobacco Surveillance System (GTSS) for continuous tobacco control
      surveillance and monitoring. Foreword.

PMID- 19770233
TI  - Evolution of the Global Tobacco Surveillance System (GTSS) 1998-2008.
AB  - Tobacco use is one of the leading preventable causes of morbidity and mortality
      worldwide. Given that country-specific international data on tobacco use were
      limited or nonexistent, in 1998, the World Health Organization (WHO), the Centers
      for Disease Control and Prevention (CDC), and the Canadian Public Health
      Association (CPHA) initiated the Global Tobacco Surveillance System (GTSS) to
      assist countries in establishing tobacco control surveillance and monitoring
      programs. GTSS includes collection of data through three school-based surveys:
      the Global Youth Tobacco Survey (GYTS) for youth; the Global School Personnel
      Survey (GSPS), and the Global Health Professions Student Survey (GHPSS) for
      adults; and one household survey: the Global Adult Tobacco Survey (GATS) for
      adults. The GTSS provides a globally implemented and consistent framework for
      conducting surveillance including standard sampling procedures, core
      questionnaire items, training in field procedures and analysis of data consistent
      across all GTSS countries. The GTSS also enhances the role of the nongovernmental
      sector by supporting participation of civil society agencies in surveillance,
      monitoring, and policy and program development. The synergy between countries
      passing tobacco control laws, regulations or decrees, ratifying and complying
      with the WHO Framework Convention on Tobacco Control, and conducting GTSS surveys
      offers a unique opportunity to develop, implement, and evaluate comprehensive
      tobacco control policy that can be helpful to each country document the
      development, growth, and collaboration in sustaining the GTSS. The report
      highlights countries' involvement in tobacco control measures and the
      establishment of comprehensive tobacco control programs worldwide. This report
      can assist countries in prioritizing and developing tobacco control programs,
      including surveillance, evaluation, and policy development.

PMID- 19770234
TI  - Change in tobacco use among 13-15 year olds between 1999 and 2008: findings from
      the Global Youth Tobacco Survey.
AB  - Tobacco use is the leading preventable cause of death and disease in the world;
      yet little is known about the levels or patterns of youth tobacco use on a global
      basis. The purpose of this paper is to focus on change in youth tobacco use using
      data from 100 sites that have conducted repeat Global Youth Tobacco Surveys
      (GYTS). The GYTS is a school-based survey that collects data from students aged
      13-15 years using a standardized methodology for constructing the sample frame,
      selecting schools and classes, and processing data. GYTS is conducted in school
      classes using self-administered anonymous data collection. The GYTS sample
      produces representative, independent, cross-sectional estimates for each sampling
      frame. Of the 100 sites surveyed, 61 reported no change over time in prevalence
      of cigarette smoking, likewise in 50 of the 97 sites with data on use of other
      tobacco products there was no change. However, 34 sites reported an increase in
      other tobacco use. This appears to be attributed to waterpipe, an emerging trend
      in tobacco use. Evidence was found supporting the idea that tobacco use among
      adolescent girls is likely increasing. The global tobacco control effort
      continues to face many challenges in reversing the tobacco epidemic. Few
      countries have implemented comprehensive tobacco control legislation laid out by
      the World Health Organization. The few countries that have adopted some of these
      proven policies can serve as examples in achieving positive results in curbing
      the tobacco epidemic.

PMID- 19770238
TI  - Humanizing the hospital: design lessons from a Finnish sanatorium.

PMID- 19770237
TI  - Seasonality of mortality: the September phenomenon in Mediterranean countries.
AB  - BACKGROUND: Seasonal increases in the mortality rate have been associated with
      excessively cold or hot weather. We evaluated monthly patterns of mortality in
      selected countries. METHODS: We analyzed all-cause mortality statistics from 5
      European Mediterranean countries (Cyprus, France, Greece, Italy, Spain), Sweden,
      North America (United States and Canada), Australia, New Zealand and Japan. We
      extracted and tabulated data on monthly all-cause mortality in the general
      population from the earliest to the latest year that records were available.
      RESULTS: We identified relevant data for a period of 2-57 years in each country.
      In the Mediterranean countries, the lowest average daily mortality was observed
      in September (all countries, 125/168 [74%] years). The fewest deaths were in
      August in Sweden (14/20 [70%] years) and North America (32/50 [64%] years). The
      fewest deaths in Japan occurred in July (2/2 [100%] years). In the southern
      hemisphere, the lowest mortality in Australia occurred in March (7/10 [70%]
      years) and in February for New Zealand (cumulative over 24 years).
      INTERPRETATION: Mortality in the general population declines in the late summer
      to early fall months in the countries evaluated. Environmental parameters may
      partly account for these associations, and further research is needed on the
      contribution of additional factors such as summer vacations.

PMID- 19770240
TI  - Clinical Images: Yellow nail syndrome.

PMID- 19770242
TI  - Physician mobility remains a "moving target".

PMID- 19770241
TI  - Diagnosis of asthma in adults.

PMID- 19770243
TI  - New student medical journal launched.

PMID- 19770244
TI  - Flu vaccination campaign poses monitoring difficulties.

PMID- 19770245
TI  - Survey reveals health impact of downturn.

PMID- 19770246
TI  - Out, damn Spot.

PMID- 19770247
TI  - Flu pandemic prompts other vaccination delays.

PMID- 19770248
TI  - Prevalence of ghostwriting spurs calls for transparency.

PMID- 19770249
TI  - Euthanasia debate reignited.

PMID- 19770250
TI  - Opioid prescribing challenges doctors.

PMID- 19770251
TI  - Ontario takes aim at painkiller abuse.

PMID- 19770252
TI  - Regulatory colleges to set painkiller guidelines.

PMID- 19770253
TI  - Public reports of infection rates urged.

PMID- 19770254
TI  - Dispensing antivirals in underserved communities.

PMID- 19770255
TI  - Swine flu breaks out on Vancouver Island.

PMID- 19770256
TI  - Improved flu screening needed at airports.

PMID- 19770257
TI  - Internet addiction: New-age diagnosis or symptom of age-old problem?

PMID- 19770258
TI  - Virtual detox: Inpatient therapy for Internet addicts.

PMID- 19770259
TI  - Dispatch from the medical front: Short-lived joy.

PMID- 19770260
TI  - CMA transformation initiative scrutinized.

PMID- 19770261
TI  - Dalhousie University medical school faces probation.

PMID- 19770262
TI  - Reproducing the manual annotation of multiple sequence alignments using a SVM
      classifier.
AB  - MOTIVATION: Aligning protein sequences with the best possible accuracy requires
      sophisticated algorithms. Since the optimal alignment is not guaranteed to be the
      correct one, it is expected that even the best alignment will contain sites that
      do not respect the assumption of positional homology. Because formulating rules
      to identify these sites is difficult, it is common practice to manually remove
      them. Although considered necessary in some cases, manual editing is time
      consuming and not reproducible. We present here an automated editing method based
      on the classification of 'valid' and 'invalid' sites. RESULTS: A support vector
      machine (SVM) classifier is trained to reproduce the decisions made during manual
      editing with an accuracy of 95.0%. This implies that manual editing can be made
      reproducible and applied to large-scale analyses. We further demonstrate that it
      is possible to retrain/extend the training of the classifier by providing
      examples of multiple sequence alignment (MSA) annotation. Near optimal training
      can be achieved with only 1000 annotated sites, or roughly three samples of
      protein sequence alignments. AVAILABILITY: This method is implemented in the
      software MANUEL, licensed under the GPL. A web-based application for single and
      batch job is available at http://fester.cs.dal.ca/manuel. SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online.

PMID- 19770264
TI  - Bioactive Markers Based Pharmacokinetic Evaluation of Extracts of a Traditional
      Medicinal Plant, Piper sarmentosum.
AB  - In vitro assays are economical and easy to perform but to establish relevance of
      their results to real clinical outcome in animals or human, pharmacokinetics is
      prerequisite. Despite various in vitro pharmacological activities of extracts of
      Piper sarmentosum, there is no report of pharmacokinetics. Therefore, the present
      study aimed to evaluate ethanol extract of fruit of the plant in dose of 500 mg
      kg(-1) orally for pharmacokinetics. Sprague-Dawley rats were randomly divided
      into groups 1, 2, and 3 (each n = 6) to study absorption, distribution and
      excretion, respectively. High performance liquid chromatography (HPLC) with
      ultraviolet detection was applied to quantify pellitorine, sarmentine and
      sarmentosine in plasma, tissues, feces and urine to calculate pharmacokinetic
      parameters. Pellitorine exhibited maximum plasma concentration (C(max)) 34.77 ng
      mL(-1) +/- 1.040, time to achieve C(max) (T(max)) 8 h, mean resident time (MRT)
      26.00 +/- 0.149 h and half life (t(1/2)) 18.64 +/- 1.65 h. Sarmentine showed
      C(max) 191.50 +/- 12.69 ng mL(-1), T(max) 6 h, MRT 11.12 +/- 0.44 h and t(1/2)
      10.30 +/- 1.98 h. Sarmentosine exhibited zero oral bioavailability because it was
      neither detected in plasma nor in tissues, and in urine. Pellitorine was found to
      be distributed in intestinal wall, liver, lungs, kidney, and heart, whereas
      sarmentine was found only in intestinal wall and heart. The cumulative excretion
      of pellitorine, sarmentine and sarmentosine in feces in 72 h was 0.0773, 0.976,
      and 0.438 MUg, respectively. This study shows that pellitorine and sarmentine
      have good oral bioavailability while sarmentosine is not absorbed from the
      gastrointestinal tract.

PMID- 19770263
TI  - How and when should interactome-derived clusters be used to predict functional
      modules and protein function?
AB  - MOTIVATION: Clustering of protein-protein interaction networks is one of the most
      common approaches for predicting functional modules, protein complexes and
      protein functions. But, how well does clustering perform at these tasks? RESULTS:
      We develop a general framework to assess how well computationally derived
      clusters in physical interactomes overlap functional modules derived via the Gene
      Ontology (GO). Using this framework, we evaluate six diverse network clustering
      algorithms using Saccharomyces cerevisiae and show that (i) the performances of
      these algorithms can differ substantially when run on the same network and (ii)
      their relative performances change depending upon the topological characteristics
      of the network under consideration. For the specific task of function prediction
      in S.cerevisiae, we demonstrate that, surprisingly, a simple non-clustering guilt
      by-association approach outperforms widely used clustering-based approaches that
      annotate a protein with the overrepresented biological process and cellular
      component terms in its cluster; this is true over the range of clustering
      algorithms considered. Further analysis parameterizes performance based on the
      number of annotated proteins, and suggests when clustering approaches should be
      used for interactome functional analyses. Overall our results suggest a re
      examination of when and how clustering approaches should be applied to physical
      interactomes, and establishes guidelines by which novel clustering approaches for
      biological networks should be justified and evaluated with respect to functional
      analysis. SUPPLEMENTARY INFORMATION: Supplementary data are available at
      Bioinformatics online.

PMID- 19770265
TI  - Anti-Arthritic Activity of Bartogenic Acid Isolated from Fruits of Barringtonia
      racemosa Roxb. (Lecythidaceae).
AB  - The fruits of Barringtonia racemosa are prescribed in the ayurvedic literature
      for the treatment of pain, inflammation and rheumatic conditions. In present
      investigation, activity guided isolation of bartogenic acid (BA) and its
      evaluation in the Complete Freund's Adjuvant (CFA)-induced arthritis in rats is
      reported. Among the various extracts and fractions investigated preliminarily for
      carrageenan-induced acute inflammation in rats, the ethyl acetate fraction
      displayed potent anti-inflammatory activity. Large-scale isolation and
      characterization using chromatography and spectral study confirmed that the
      constituent responsible for the observed pharmacological effects was BA.
      Subsequently the BA was evaluated for effectiveness against CFA-induced arthritis
      in rats. The results indicate that at doses of 2, 5, and 10 mg kg(-1) day(-1),
      p.o., BA protects rats against the primary and secondary arthritic lesions, body
      weight changes and haematological perturbations induced by CFA. The serum markers
      of inflammation and arthritis, such as C-reactive protein and rheumatoid factor,
      were also reduced in the BA-treated arthritic rats. The overall severity of
      arthritis as determined by radiological analysis and pain scores indicated that
      BA exerts a potent protective effect against adjuvant-induced arthritis in rats.
      In conclusion, the present study validates the ethnomedicinal use of fruits of B.
      racemosa in the treatment of pain and inflammatory conditions. It further
      establishes the potent anti-arthritic effects of BA. However, additional clinical
      investigations are needed to prove the efficacy of BA in the treatment of various
      immuno-inflammatory disorders.

PMID- 19770266
TI  - Antimicrobial and antioxidant activities of plants from northeast of Mexico.
AB  - Traditional medicine has a key role in health care worldwide. Obtaining
      scientific information about the efficacy and safety of the plants from our
      region is one of the goals of our research group. In this report, 17 plants were
      selected and collected in different localities from northeast Mexico. The dried
      plants were separated into leaves, flowers, fruit, stems, roots and bark. Each
      part was extracted with methanol, and 39 crude extracts were prepared. The
      extracts were tested for their antimicrobial activity using three Gram-negative
      bacterial strains (Pseudomonas aeruginosa, Klebsiella pneumoniae and
      Acinetobacter baumannii), three Gram-positive bacterial strains (Enterococcus
      faecalis and two Staphylococcus aureus strains), and seven clinically isolated
      yeasts (Candida albicans, C. krusei, C. tropicalis, C. parapsilosis and C.
      glabrata); their antioxidant activity was tested using a DPPH free radical assay.
      No activity against Gram-negative bacteria was observed with any extract up to
      the maximum concentration tested, 1000 MUg ml(-1). We report here for the first
      time activity of Ceanothus coeruleus against S. aureus (flowers, minimal
      inhibitory concentration (MIC) 125 MUg ml(-1)), C. glabrata (MICs 31.25 MUg ml(
      1)) and C. parapsilosis (MICs between 31.25 and 125 MUg ml(-1)); Chrysanctinia
      mexicana against C. glabrata (MICs 31.25 MUg ml(-1)); Colubrina greggii against
      E. faecalis (MICs 250 MUg ml(-1)) and Cordia boissieri against C. glabrata (MIC
      125 MUg ml(-1)). Furthermore, this is the first report about antioxidant activity
      of extracts from Ceanothus coeruleus, Chrysanctinia mexicana, Colubrina greggii
      and Cyperus alternifolius. Some correlation could exist between antioxidant
      activity and antiyeast activity against yeasts in the species Ceanothus
      coeruleus, Schinus molle, Colubrina greggii and Cordia boissieri.

PMID- 19770269
TI  - TSLP and IL-7 use two different mechanisms to regulate human CD4+ T cell
      homeostasis.
AB  - Whether thymic stromal lymphopoietin (TSLP) directly induces potent human CD4(+)
      T cell proliferation and Th2 differentiation is unknown. We report that resting
      and activated CD4(+) T cells expressed high levels of IL-7 receptor a chain but
      very low levels of TSLP receptor (TSLPR) when compared with levels expressed in
      myeloid dendritic cells (mDCs). This was confirmed by immunohistology and flow
      cytometry analyses showing that only a subset of mDCs, with more activated
      phenotypes, expressed TSLPR in human tonsils in vivo. IL-7 induced strong STAT1, 
      3, and -5 activation and promoted the proliferation of naive CD4(+) T cells in
      the presence of anti-CD3 and anti-CD28 monoclonal antibodies, whereas TSLP
      induced weak STAT5 activation, associated with marginally improved cell survival
      and proliferation, but failed to induce cell expansion and Th2 differentiation.
      The effect of TSLP on enhancing strong human T cell proliferation was observed
      only when sorted naive CD4(+) T cells were cultured with mDCs at levels as low as
      0.5%. TSLP could only induce naive CD4(+) T cells to differentiate into Th2 cells
      in the presence of allogeneic mDCs. These results demonstrate that IL-7 and TSLP
      use different mechanisms to regulate human CD4(+) T cell homeostasis.

PMID- 19770268
TI  - A murine DC-SIGN homologue contributes to early host defense against
      Mycobacterium tuberculosis.
AB  - The C-type lectin dendritic cell-specific intercellular adhesion molecule-3
      grabbing nonintegrin (DC-SIGN) mediates the innate immune recognition of
      microbial carbohydrates. We investigated the function of this molecule in the
      host response to pathogens in vivo, by generating mouse lines lacking the DC-SIGN
      homologues SIGNR1, SIGNR3, and SIGNR5. Resistance to Mycobacterium tuberculosis
      was impaired only in SIGNR3-deficient animals. SIGNR3 was expressed in lung
      phagocytes during infection, and interacted with M. tuberculosis bacilli and
      mycobacterial surface glycoconjugates to induce secretion of critical host
      defense inflammatory cytokines, including tumor necrosis factor (TNF). SIGNR3
      signaling was dependent on an intracellular tyrosine-based motif and the tyrosine
      kinase Syk. Thus, the mouse DC-SIGN homologue SIGNR3 makes a unique contribution
      to protection of the host against a pulmonary bacterial pathogen.

PMID- 19770270
TI  - Nonaminoglycoside compounds induce readthrough of nonsense mutations.
AB  - Large numbers of genetic disorders are caused by nonsense mutations for which
      compound-induced readthrough of premature termination codons (PTCs) might be
      exploited as a potential treatment strategy. We have successfully developed a
      sensitive and quantitative high-throughput screening (HTS) assay, protein
      transcription/translation (PTT)-enzyme-linked immunosorbent assay (ELISA), for
      identifying novel PTC-readthrough compounds using ataxia-telangiectasia (A-T) as
      a genetic disease model. This HTS PTT-ELISA assay is based on a coupled PTT that
      uses plasmid templates containing prototypic A-T mutated (ATM) mutations for HTS.
      The assay is luciferase independent. We screened approximately 34,000 compounds
      and identified 12 low-molecular-mass nonaminoglycosides with potential PTC
      readthrough activity. From these, two leading compounds consistently induced
      functional ATM protein in ATM-deficient cells containing disease-causing nonsense
      mutations, as demonstrated by direct measurement of ATM protein, restored ATM
      kinase activity, and colony survival assays for cellular radiosensitivity. The
      two compounds also demonstrated readthrough activity in mdx mouse myotube cells
      carrying a nonsense mutation and induced significant amounts of dystrophin
      protein.

PMID- 19770271
TI  - Pathogenicity of a disease-associated human IL-4 receptor allele in experimental
      asthma.
AB  - Polymorphisms in the interleukin-4 receptor alpha chain (IL-4R alpha) have been
      linked to asthma incidence and severity, but a causal relationship has remained
      uncertain. In particular, a glutamine to arginine substitution at position 576
      (Q576R) of IL-4R alpha has been associated with severe asthma, especially in
      African Americans. We show that mice carrying the Q576R polymorphism exhibited
      intense allergen-induced airway inflammation and remodeling. The Q576R
      polymorphism did not affect proximal signal transducer and activator of
      transcription (STAT) 6 activation, but synergized with STAT6 in a gene target-
      and tissue-specific manner to mediate heightened expression of a subset of IL-4-
      and IL-13-responsive genes involved in allergic inflammation. Our findings
      indicate that the Q576R polymorphism directly promotes asthma in carrier
      populations by selectively augmenting IL-4R alpha-dependent signaling.

PMID- 19770272
TI  - Regulation of pathogenesis and immunity in helminth infections.
AB  - Helminths are multicellular eukaryotic parasites that infect over one quarter of
      the world's population. Through coevolution with the human immune system, these
      organisms have learned to exploit immunoregulatory pathways, resulting in
      asymptomatic tolerance of infections in many individuals. When infections and the
      resulting immune responses become dysregulated, however, acute and chronic
      pathologies often develop. A recent international meeting focused on how these
      parasites modulate host immunity and how control of parasitic and
      immunopathological disease might be achieved.

PMID- 19770273
TI  - Phenylbutyrate induces antimicrobial peptide expression.
AB  - Antimicrobial peptides (AMPs) are important components of our first line of
      defense. Induction of AMPs such as LL-37 of the cathelicidin family might provide
      a novel approach in treating bacterial infections. In this study we identified 4
      phenylbutyrate (PBA) as a novel inducer of AMP expression and investigated
      affected regulatory pathways. We treated various cell lines with PBA and assessed
      mRNA expression by real-time reverse transcriptase PCR (RT-PCR). Cathelicidin AMP
      (CAMP) gene expression was found to be upregulated in all four cell lines tested.
      Additionally, we found that the beta-defensin 1 gene was upregulated in the lung
      epithelial cell line VA10 while being downregulated in the monocytic cell line
      U937. Further we found that PBA induced CAMP gene expression synergistically with
      1,25-dihydroxyvitamin D(3) at both protein and mRNA levels. The general mechanism
      of induction of CAMP gene expression by PBA was found to be dependent on protein
      synthesis. Results from quantitative chromatin immunoprecipitation experiments
      challenge the common view that histone deacetylase inhibitors directly increase
      CAMP gene expression. Furthermore, we have demonstrated that inhibition of the
      mitogen-activated protein kinases MEK1/2 and c-Jun N-terminal kinase attenuate
      PBA-induced CAMP gene expression. Similarly, alpha-methylhydrocinnamate (ST7), an
      analogue of PBA, increases CAMP gene expression. Our findings contribute to
      understanding of the regulation of AMP expression and suggest that PBA and/or ST7
      is a promising drug candidate for treatment of microbial infections by
      strengthening the epithelial antimicrobial barriers.

PMID- 19770274
TI  - Inhibition of herpesvirus replication by 5-substituted 4'-thiopyrimidine
      nucleosides.
AB  - A series of 4'-thionucleosides were synthesized and evaluated for activities
      against orthopoxviruses and herpesviruses. We reported previously that one
      analog, 5-iodo-4'-thio-2'-deoxyuridine (4'-thioIDU), exhibits good activity both
      in vitro and in vivo against two orthopoxviruses. This compound also has good
      activity in cell culture against many of the herpesviruses. It inhibited the
      replication of herpes simplex virus type 1 (HSV-1), HSV-2, and varicella-zoster
      virus with 50% effective concentrations (EC(50)s) of 0.1, 0.5, and 2 microM,
      respectively. It also inhibited the replication of human cytomegalovirus (HCMV)
      with an EC(50) of 5.9 microM but did not selectively inhibit Epstein-Barr virus,
      human herpesvirus 6, or human herpesvirus 8. While acyclovir-resistant strains of
      HSV-1 and HSV-2 were comparatively resistant to 4'-thioIDU, it retained modest
      activity (EC(50)s of 4 to 12 microM) against these strains. Some ganciclovir
      resistant strains of HCMV also exhibited reduced susceptibilities to the
      compound, which appeared to be related to the specific mutations in the DNA
      polymerase, consistent with the observed incorporation of the compound into viral
      DNA. The activity of 4'-thioIDU was also evaluated using mice infected
      intranasally with the MS strain of HSV-2. Although there was no decrease in final
      mortality rates, the mean length of survival after inoculation increased
      significantly (P < 0.05) for all animals receiving 4'-thioIDU. The findings from
      the studies presented here suggest that 4'-thioIDU is a good inhibitor of some
      herpesviruses, as well as orthopoxviruses, and this class of compounds warrants
      further study as a therapy for infections with these viruses.

PMID- 19770275
TI  - Characterization of a new metallo-beta-lactamase gene, bla(NDM-1), and a novel
      erythromycin esterase gene carried on a unique genetic structure in Klebsiella
      pneumoniae sequence type 14 from India.
AB  - A Swedish patient of Indian origin traveled to New Delhi, India, and acquired a
      urinary tract infection caused by a carbapenem-resistant Klebsiella pneumoniae
      strain that typed to the sequence type 14 complex. The isolate, Klebsiella
      pneumoniae 05-506, was shown to possess a metallo-beta-lactamase (MBL) but was
      negative for previously known MBL genes. Gene libraries and amplification of
      class 1 integrons revealed three resistance-conferring regions; the first
      contained bla(CMY-4) flanked by ISEcP1 and blc. The second region of 4.8 kb
      contained a complex class 1 integron with the gene cassettes arr-2, a new
      erythromycin esterase gene; ereC; aadA1; and cmlA7. An intact ISCR1 element was
      shown to be downstream from the qac/sul genes. The third region consisted of a
      new MBL gene, designated bla(NDM-1), flanked on one side by K. pneumoniae DNA and
      a truncated IS26 element on its other side. The last two regions lie adjacent to
      one another, and all three regions are found on a 180-kb region that is easily
      transferable to recipient strains and that confers resistance to all antibiotics
      except fluoroquinolones and colistin. NDM-1 shares very little identity with
      other MBLs, with the most similar MBLs being VIM-1/VIM-2, with which it has only
      32.4% identity. As well as possessing unique residues near the active site, NDM-1
      also has an additional insert between positions 162 and 166 not present in other
      MBLs. NDM-1 has a molecular mass of 28 kDa, is monomeric, and can hydrolyze all
      beta-lactams except aztreonam. Compared to VIM-2, NDM-1 displays tighter binding
      to most cephalosporins, in particular, cefuroxime, cefotaxime, and cephalothin
      (cefalotin), and also to the penicillins. NDM-1 does not bind to the carbapenems
      as tightly as IMP-1 or VIM-2 and turns over the carbapenems at a rate similar to
      that of VIM-2. In addition to K. pneumoniae 05-506, bla(NDM-1) was found on a 140
      kb plasmid in an Escherichia coli strain isolated from the patient's feces,
      inferring the possibility of in vivo conjugation. The broad resistance carried on
      these plasmids is a further worrying development for India, which already has
      high levels of antibiotic resistance.

PMID- 19770276
TI  - The final step of hygromycin A biosynthesis, oxidation of C-5''-dihydrohygromycin
      A, is linked to a putative proton gradient-dependent efflux.
AB  - Hygromycin A (HA) is an aminocyclitol antibiotic produced and excreted by
      Streptomyces hygroscopicus. Deletion of hyg26 from the hygromycin A biosynthetic
      gene cluster has previously been shown to result in a mutant that produces 5''
      dihydrohygromycin A (DHHA). We report herein on the purification and
      characterization of Hyg26 expressed in Escherichia coli. The enzyme catalyzes an
      NAD(H)-dependent reversible interconversion of HA and DHHA, supporting the role
      of the reduced HA as the penultimate biosynthetic pathway intermediate and not a
      shunt product. The equilibrium for the Hyg26-catalyzed reaction heavily favors
      the DHHA intermediate. The high-titer production of the HA product by S.
      hygroscopicus must be dependent upon a subsequent energetically favorable enzyme
      catalyzed process, such as the selective and efficient export of HA. hyg19
      encodes a putative proton gradient-dependent transporter, and a mutant lacking
      this gene was observed to produce less HA and to produce the DHHA intermediate.
      The DHHA produced by either the Deltahyg19 or the Deltahyg26 mutant had slightly
      reduced activity against E. coli and reduced protein synthesis-inhibitory
      activity in vitro. The data indicate that Hyg26 and Hyg19 have evolved to produce
      and export the final potent HA product in a coordinated fashion.

PMID- 19770277
TI  - Activity of the novel peptide arminin against multiresistant human pathogens
      shows the considerable potential of phylogenetically ancient organisms as drug
      sources.
AB  - The emergence of multidrug-resistant bacteria highlights the need for new
      antibacterial agents. Arminin 1a is a novel antimicrobial peptide discovered
      during investigations of the epithelial defense of the ancient metazoan Hydra.
      Following proteolytic processing, the 31-amino-acid-long positively charged C
      terminal part of arminin 1a exhibits potent and broad-spectrum activity against
      bacteria, including multiresistant human pathogenic strains, such as methicillin
      resistant Staphylococcus aureus (MRSA) strains (minimal bactericidal
      concentration, 0.4 microM to 0.8 microM). Ultrastructural observations indicate
      that bacteria are killed by disruption of the bacterial cell wall. Remarkably,
      the antibacterial activity of arminin 1a is not affected under the physiological
      salt conditions of human blood. In addition, arminin 1a is a selective
      antibacterial agent that does not affect human erythrocyte membranes. Arminin 1a
      shows no sequence homology to any known antimicrobial peptide. Because of its
      high level of activity against multiresistant bacterial strains pathogenic for
      humans, the peptide arminin 1a is a promising template for a new class of
      antibiotics. Our data suggest that ancient metazoan organisms such as Hydra hold
      promise for the detection of novel antimicrobial molecules and the treatment of
      infections caused by multiresistant bacteria.

PMID- 19770278
TI  - Detection of the novel extended-spectrum beta-lactamase OXA-161 from a plasmid
      located integron in Pseudomonas aeruginosa clinical isolates from Spain.
AB  - Two clonally related Pseudomonas aeruginosa isolates, recovered from two patients
      admitted to a pediatric intensive care unit, were found to harbor a new OXA-2
      variant (Asn148Asp), designated OXA-161. The plasmid location of bla(OXA-161) was
      demonstrated through electroporation to PAO1, and its codification in a class I
      integron (together with aacA4) was demonstrated through PCR and sequencing.
      bla(OXA-2) and bla(OXA-161) were cloned in parallel to demonstrate the extended
      spectrum beta-lactamase properties of OXA-161, conferring resistance to
      ceftazidime and reduced susceptibility to cefepime and aztreonam.

PMID- 19770279
TI  - OXA-143, a novel carbapenem-hydrolyzing class D beta-lactamase in Acinetobacter
      baumannii.
AB  - A carbapenem-resistant Acinetobacter baumannii strain was isolated in Brazil in
      2004 in which no known carbapenemase gene was detected by PCR. Cloning
      experiments, followed by expression in Escherichia coli, gave an E. coli
      recombinant strain expressing a novel carbapenem-hydrolyzing class D beta
      lactamase (CHDL). OXA-143 showed 88% amino acid sequence identity with OXA-40,
      63% identity with OXA-23, and 52% identity with OXA-58. It hydrolyzed
      penicillins, oxacillin, meropenem, and imipenem but not expanded-spectrum
      cephalosporins. The bla(OXA-143) gene was located on a ca. 30-kb plasmid. After
      transformation into reference strain A. baumannii ATCC 19606, it conferred
      resistance to carbapenems. Analysis of the genetic environment of bla(OXA-143)
      revealed that it was associated with neither insertion sequences nor integron
      structures. However, it was bracketed by similar replicase-encoding genes at both
      ends, suggesting acquisition through a homologous recombination process. This
      study identified a novel class D beta-lactamase involved in carbapenem resistance
      in A. baumannii. This enzyme is the first member of a novel subgroup of CHDLs
      whose prevalence remains to be determined.

PMID- 19770280
TI  - Role of AbeS, a novel efflux pump of the SMR family of transporters, in
      resistance to antimicrobial agents in Acinetobacter baumannii.
AB  - In this study, a chromosomally encoded putative drug efflux pump of the SMR
      family, named AbeS, from a multidrug-resistant strain of Acinetobacter baumannii
      was characterized to elucidate its role in antimicrobial resistance. Expression
      of the cloned abeS gene in hypersensitive Escherichia coli host KAM32 resulted in
      decreased susceptibility to various classes of antimicrobial agents, detergents,
      and dyes. Deletion of the abeS gene in A. baumannii confirmed its role in
      conferring resistance to these compounds.

PMID- 19770281
TI  - Randomized controlled study investigating viral suppression and serological
      response following pre-S1/pre-S2/S vaccine therapy combined with lamivudine
      treatment in HBeAg-positive patients with chronic hepatitis B.
AB  - The aim of the current study was to evaluate viral suppression following combined
      treatment with an S/pre-S1/pre-S2 vaccine and lamivudine in patients with chronic
      hepatitis B. We established a randomized, controlled clinical trial to compare
      the responses of three different treatment groups: those receiving vaccine
      monotherapy, lamivudine monotherapy, or combination treatment. Viral response was
      evaluated via hepatitis B virus (HBV) DNA suppression using different levels of
      classification. Seroconversion was evaluated via HBeAg loss, HBeAg
      seroconversion, HBsAg loss, and anti-HBs response. We found that the group
      receiving combination treatment demonstrated a significant increase in viral
      suppression over that for the lamivudine or vaccine monotherapy group, although
      the HBeAg seroconversion rate was not different. This enhanced suppression effect
      in the combination group was reversed after the discontinuation of vaccine
      treatment, suggesting that booster doses are required for a sustained viral
      response. Anti-HBs was detected in 55/120 vaccine recipients, but only 3 patients
      demonstrated HBsAg loss, indicating that the vaccine-induced anti-HBs was unable
      to completely neutralize HBsAg in the serum. At the study end point, anti-HBs
      responders showed significantly higher HBeAg seroconversion rates, greater
      suppression of HBV DNA levels, and a lower median reduction in HBV DNA levels
      than those of anti-HBs nonresponders. Our results suggest that combined treatment
      with the vaccine and lamivudine was significantly more effective than lamivudine
      monotherapy in the short term and was especially successful in producing viral
      suppression and an enhanced anti-HBs antibody response.

PMID- 19770282
TI  - In vitro activities of piperaquine, lumefantrine, and dihydroartemisinin in
      Kenyan Plasmodium falciparum isolates and polymorphisms in pfcrt and pfmdr1.
AB  - We have analyzed the in vitro chemosensitivity profiles of 115 Kenyan isolates
      for chloroquine (CQ), piperaquine, lumefantrine (LM), and dihydroartemisinin in
      association with polymorphisms in pfcrt at codon 76 and pfmdr1 at codon 86, as
      well as with variations of the copy number of pfmdr1. The median drug
      concentrations that inhibit 50% of parasite growth (IC(50)s) were 41 nM
      (interquartile range [IQR], 18 to 73 nM), 50 nM (IQR, 29 to 96 nM), 32 nM (IQR,
      17 to 46 nM), and 2 nM (IQR, 1 to 3 nM) for CQ, LM, piperaquine, and
      dihydroartemisinin, respectively. The activity of CQ correlated inversely with
      that of LM (r(2) = -0.26; P = 0.02). Interestingly, parasites for which LM
      IC(50)s were higher were wild type for pfcrt-76 and pfmdr1-86. All isolates had
      one pfmdr1 copy. Thus, the decrease in LM activity is associated with the
      selection of wild-type pfcrt-76 and pfmdr1-86 parasites, a feature that accounts
      for the inverse relationship between CQ and LM. Therefore, the use of LM
      artemether is likely to lead to the selection of more CQ-susceptible parasites.

PMID- 19770283
TI  - The antituberculosis drug pyrazinamide affects the course of cutaneous
      leishmaniasis in vivo and increases activation of macrophages and dendritic
      cells.
AB  - Antileishmanial therapy is suboptimal due to toxicity, high cost, and development
      of resistance to available drugs. Pyrazinamide (PZA) is a constituent of short
      course tuberculosis chemotherapy. We investigated the effect of PZA on Leishmania
      major promastigote and amastigote survival. Promastigotes were more sensitive to
      the drug than amastigotes, with concentrations at which 50% of parasites were
      inhibited (MIC(50)) of 16.1 and 8.2 microM, respectively (48 h posttreatment).
      Moreover, 90% of amastigotes were eliminated at 120 h posttreatment, indicating
      that longer treatments will result in parasite elimination. Most strikingly, PZA
      treatment of infected C57BL/6 mice resulted in protection against disease and in
      a 100-fold reduction in the parasite burden. PZA treatment of J774 cells and bone
      marrow-derived dendritic cells and macrophages increased interleukin 12, tumor
      necrosis factor alpha, and activation marker expression, as well as nitric oxide
      production, suggesting that PZA enhances effective immune responses against the
      parasite. PZA treatment also activates dendritic cells deficient in Toll-like
      receptor 2 and 4 expression to initiate a proinflammatory response, confirming
      that the immunostimulatory effect of PZA is directly caused by the drug and is
      independent of Toll-like receptor stimulation. These results not only are
      strongly indicative of the promise of PZA as an alternative antileishmanial
      chemotherapy but also suggest that PZA causes collateral immunostimulation, a
      phenomenon that has never been reported for this drug.

PMID- 19770285
TI  - Rapid automatized naming and immediate memory functions in Chinese Mandarin
      speaking elementary readers.
AB  - The purpose of this study was to evaluate rapid automatized naming skills (RAN)
      and immediate memory processes in 243 Chinese Mandarin-speaking elementary
      readers (ranging from Grade 1 to Grade 5). For RAN subtests, the mean naming time
      decreased monotonically with grade level in good and average readers, and a
      similar trajectory was found in poor readers, even though they were generally
      slower in rapid naming. Regardless of grouping methods (counting all participants
      or counting good readers only), RAN Character emerged as a significant predictor
      of various Chinese reading measures. Different from classical findings in English
      readers indicating that RAN Number was a better correlate of reading than RAN
      Object, RAN Object outperformed RAN Number and became a significant predictor of
      Chinese reading speed and spelling, suggesting that the differences in predictive
      power of RAN tasks may be language specific. Comparison of memory profiles for
      good, average, and poor readers revealed that the patterns varied depending on
      mode of stimulus presentation or response. Poor readers performed poorly on
      subtests involving a visual component and did relatively better on subtests
      involving verbal cues only, whereas a reversed pattern was shown in the group of
      good readers. The findings were interpreted to suggest that good and poor Chinese
      readers may be essentially different in applying visual strategies and verbal
      mediation during visual-verbal intra- and intermodal processing, and visual
      skills appear to be particularly important in reading of Chinese.

PMID- 19770284
TI  - Bronchopulmonary disposition of intravenous voriconazole and anidulafungin given
      in combination to healthy adults.
AB  - Voriconazole and anidulafungin in combination are being investigated for use for
      the treatment of pulmonary aspergillosis. We determined the pulmonary disposition
      of these agents. Twenty healthy participants received intravenous voriconazole
      (at 6 mg/kg of body weight every 12 h [q12h] on day 1 and then at 4 mg/kg q12h)
      and anidulafungin (200 mg on day 1 and then 100 mg every 24 h) for 3 days. Five
      participants each were randomized for collection of bronchoalveolar lavage
      samples at times of 4, 8, 12, and 24 h. Drug penetration was determined by the
      ratio of the total drug area under the concentration-time curve during the dosing
      interval (AUC(0-tau)) for epithelial lining fluid (ELF) and alveolar macrophages
      (AM) to the total drug AUC(0-tau) in plasma. The mean (standard deviation) half
      life and AUC(0-tau) were 6.9 (2.1) h and 39.5 (19.8) microg h/ml, respectively,
      for voriconazole and 20.8 (3.1) h and 101 (21.8) microg h/ml, respectively, for
      anidulafungin. The AUC(0-tau) values for ELF and AM were 282 and 178 microg h/ml,
      respectively, for voriconazole, and 21.9 and 1,430 microg h/ml, respectively, for
      anidulafungin. This resulted in penetration ratios into ELF and AM of 7.1 and
      4.5, respectively, for voriconazole and 0.22 and 14.2, respectively, for
      anidulafungin. The mean total concentrations of both drugs in ELF and AM at 4, 8,
      12, and 24 h remained above the MIC(90)/90% minimum effective concentration for
      most Aspergillus species. In healthy adult volunteers, voriconazole achieved high
      levels of exposure in both ELF and AM, while anidulafungin predominantly
      concentrated in AM.

PMID- 19770286
TI  - In vivo efficacy of 1- and 2-gram human simulated prolonged infusions of
      doripenem against Pseudomonas aeruginosa.
AB  - Doripenem is a new carbapenem antimicrobial with activity against a range of gram
      negative organisms, including Pseudomonas aeruginosa. Previous animal studies
      have shown efficacy of a 500-mg dose of doripenem given as a 4-h infusion against
      P. aeruginosa with MICs of < or = 4 microg/ml. The purpose of this study is to
      evaluate the efficacy of 1- and 2-g-dose prolonged infusions of doripenem against
      a wide range of P. aeruginosa isolates in the neutropenic murine thigh model.
      Eighteen clinical P. aeruginosa isolates (MIC range, 2 to 32 microg/ml) were
      used; 15 of these were multidrug resistant. After infection, groups of mice were
      administered doripenem doses designed to simulate the free time above the MIC
      (fT>MIC) observed in humans given 1 or 2 g of doripenem every 8 h as a 4-h
      infusion. Efficacy correlated well with published fT>MIC bactericidal targets of
      40%. After 24 h, 1- and 2-g doses achieved approximately > or = 2 log decreases
      in CFU against isolates with MICs of < or = 8 and 16 microg/ml, respectively
      (fT>MIC range, 52.5 to 95%). Results with organisms with higher MICs, where
      fT>MIC was 0%, were variable, including both increases and decreases in CFU.
      Compared with 1-g doses, statistically greater efficacy was noted for 2-g doses
      against three of the eight isolates with MICs of > or =16 microg/ml. While MIC
      distributions of P. aeruginosa at present necessitate increased exposures for
      only the most-resistant isolates, the ability of increased doses to achieve
      pharmacodynamic targets and the efficacy observed when these targets were
      attained could prove useful when these resistant isolates are encountered.

PMID- 19770287
TI  - ACHN-490, a neoglycoside with potent in vitro activity against multidrug
      resistant Klebsiella pneumoniae isolates.
AB  - The in vitro activity of ACHN-490, a novel aminoglycoside ("neoglycoside"), was
      evaluated against 102 multidrug-resistant (MDR) Klebsiella pneumoniae strains,
      including a subset of 25 strains producing the KPC carbapenemase. MIC50 values
      for gentamicin, tobramycin, and amikacin were 8 microg/ml, 32 microg/ml, and 2
      microg/ml, respectively; MIC90 values for the same antimicrobials were > or = 64
      microg/ml, > or = 64 microg/ml, and 32 microg/ml, respectively. ACHN-490 showed
      an MIC50 of 0.5 microg/ml and an MIC90 of 1 microg/ml, which are significantly
      lower than those of comparator aminoglycosides. ACHN-490 represents a promising
      aminoglycoside for the treatment of MDR K. pneumoniae isolates, including those
      producing KPC beta-lactamase.

PMID- 19770288
TI  - Postantibiotic effect of ceftaroline against gram-positive organisms.
AB  - The postantibiotic effects (PAEs), postantibiotic sub-MIC effects (PA-SMEs), and
      sub-MIC effects (SMEs) of ceftaroline, a novel injectable cephalosporin, were
      determined for 15 gram-positive organisms. The pneumococcal, staphylococcal, and
      enterococcal PAEs were 0.8 to 1.8 h, 0.7 to 2.2 h, and 0.2 to 1.1 h,
      respectively. The corresponding PA-SMEs (0.4 times the MIC) were 2.5 to 6.7 h,
      2.9 to >0.0 h, and 7.9 to >10.3 h, respectively. The PA-SMEs were longer than the
      PAEs, suggesting that sub-MIC levels extend the PAE of ceftaroline against gram
      positive cocci.

PMID- 19770289
TI  - Is vancomycin ototoxicity a significant risk?

PMID- 19770290
TI  - Relationship between antibiotic consumption and Clostridium difficile-associated
      diarrhea: an epidemiological note.

PMID- 19770292
TI  - An adipose tissue-independent insulin-sensitizing action of telmisartan: a study
      in lipodystrophic mice.
AB  - Adipose tissue plays an important role in energy balance and metabolism and is
      the major target for insulin-sensitizing peroxisome proliferator-activated
      receptor (PPAR) gamma agonists. The angiotensin II type 1 receptor blocker
      telmisartan, a partial agonist of PPAR-gamma, has been demonstrated to improve
      insulin sensitivity. However, there is uncertainty about the sites of its action.
      Here, we demonstrate that treatment with telmisartan (3 mg/kg p.o.) for 7 weeks
      decreased plasma glucose levels in oral glucose and insulin tolerance tests and
      the index of the homeostasis model assessment of insulin resistance in A-ZIP/F-1
      transgenic mice, an animal model of lipodystrophy. These effects were accompanied
      by decreases in circulating triglyceride and fatty acid levels. However, this
      treatment did not affect body weight and plasma adiponectin, leptin, and
      corticosterone levels. In A-ZIP/F-1 mouse liver the transcripts encoding PPAR
      gamma and its downstream lipogenic genes were highly up-regulated, consistent
      with increased hepatic triglyceride content and lipid droplet accumulation.
      Telmisartan reversed these effects and also down-regulated mRNAs encoding
      gluconeogenic genes. Thus, the present findings are consistent with a novel mode
      of insulin-sensitizing action of telmisartan, involving an adipose tissue
      independent pathway. Telmisartan-elicited down-regulation of hepatic expression
      of PPAR-gamma-regulated lipogenic genes is associated with amelioration of fatty
      liver.

PMID- 19770293
TI  - Periosteal reaction.

PMID- 19770294
TI  - Radiology in Italy: what is happening?

PMID- 19770291
TI  - Kisspeptin signaling in the brain.
AB  - Kisspeptin (a product of the Kiss1 gene) and its receptor (GPR54 or Kiss1r) have
      emerged as key players in the regulation of reproduction. Mutations in humans or
      genetically targeted deletions in mice of either Kiss1 or Kiss1r cause profound
      hypogonadotropic hypogonadism. Neurons that express Kiss1/kisspeptin are found in
      discrete nuclei in the hypothalamus, as well as other brain regions in many
      vertebrates, and their distribution, regulation, and function varies widely
      across species. Kisspeptin neurons directly innervate and stimulate GnRH neurons,
      which are the final common pathway through which the brain regulates
      reproduction. Kisspeptin neurons are sexually differentiated with respect to cell
      number and transcriptional activity in certain brain nuclei, and some kisspeptin
      neurons express other cotransmitters, including dynorphin and neurokinin B (whose
      physiological significance is unknown). Kisspeptin neurons express the estrogen
      receptor and the androgen receptor, and these cells are direct targets for the
      action of gonadal steroids in both male and female animals. Kisspeptin signaling
      in the brain has been implicated in mediating the negative feedback action of sex
      steroids on gonadotropin secretion, generating the preovulatory GnRH/LH surge,
      triggering and guiding the tempo of sexual maturation at puberty, controlling
      seasonal reproduction, and restraining reproductive activity during lactation.
      Kisspeptin signaling may also serve diverse functions outside of the classical
      realm of reproductive neuroendocrinology, including the regulation of metastasis
      in certain cancers, vascular dynamics, placental physiology, and perhaps even
      higher-order brain function.

PMID- 19770295
TI  - Palliative treatment of malignant esophagopulmonary fistulas with covered
      expandable metallic stents.
AB  - OBJECTIVE: The objective of our study was to evaluate the safety and clinical
      effectiveness of covered expandable metallic stents for palliative treatment of
      malignant esophagopulmonary fistulas. MATERIALS AND METHODS: Between November
      1990 and January 2008, 14 patients with fistulas between the esophagus and
      pulmonary parenchyma were treated with covered expandable metallic esophageal
      stents. The fistulas were caused by esophageal (n = 9) or bronchogenic (n = 5)
      carcinomas. At the time of stent placement, all patients had aspiration pneumonia
      and 11 had lung abscesses (79%). Technical and clinical success, fistula
      reopening, complications, and survival rates were evaluated. RESULTS: Stent
      placement was technically successful in all cases, and there were no immediate
      procedural complications. Complete fistula sealing resulting in resolution of
      aspiration symptoms (i.e., clinical success) occurred in 12 patients (86%).
      During follow-up (mean survival, 100.9 +/- 79.9 days; median survival, 65.5 days;
      range, 16-275 days), the fistula reopened in two of 12 clinical success patients.
      One patient (7%) experienced complications resulting from dyspnea due to tracheal
      compression by the esophageal stent. Although 13 patients died of aspiration
      pneumonia and the remaining patient died of cancer bleeding, none of the
      mortalities was related to the stent placement procedure. CONCLUSION: The use of
      covered expandable metallic stents appears to be safe and feasible for the
      palliative treatment of malignant esophagopulmonary fistulas.

PMID- 19770296
TI  - CT-guided biopsy of perivascular tumor encasement using simultaneous IV contrast
      enhancement.
AB  - OBJECTIVE: The purpose of our study was to describe and review the accuracy of a
      novel technique for difficult biopsy of arterial tumor encasement using
      simultaneous IV contrast enhancement and helical CT guidance for coaxial core
      needle biopsies. CONCLUSION: Diagnostic biopsy specimens can be obtained safely
      using simultaneous IV contrast-enhanced CT guidance during difficult biopsies of
      unresectable tumors encasing the celiac, superior mesenteric, or left renal
      arteries.

PMID- 19770297
TI  - Left inferior phrenic artery feeding hepatocellular carcinoma: angiographic
      anatomy using C-arm CT.
AB  - OBJECTIVE: The left inferior phrenic artery (LIPA) is one of the common
      extrahepatic collateral arteries that supply hepatocellular carcinomas (HCCs).
      The purpose of this study is to describe the anatomy of the LIPA that supplies
      HCCs using C-arm CT in 23 patients. CONCLUSION: The anteromedial limb of the
      ascending branch was present in 14 patients and accessory gastric branches were
      noted in 11 patients. The use of angiography and C-arm CT of the LIPA showed 26
      tumor feeders in 23 patients. The feeders were seen in the anteromedial limb (n =
      12), lateral limb (n = 9), anterior limb (n = 3), and descending branch (n = 2).
      The anteromedial limb of the ascending branch is a common tumor feeder of the
      LIPA and can supply HCCs located in the right liver dome. Gastric staining is
      also frequently depicted on LIPA angiography and should not be confused with
      tumor staining.

PMID- 19770298
TI  - Dynamic contrast-enhanced MRI of the breast: quantitative method for kinetic
      curve type assessment.
AB  - OBJECTIVE: The type of contrast enhancement kinetic curve (i.e., persistently
      enhancing, plateau, or washout) seen on dynamic contrast-enhanced MRI (DCE-MRI)
      of the breast is predictive of malignancy. Qualitative estimates of the type of
      curve are most commonly used for interpretation of DCE-MRI. The purpose of this
      study was to compare qualitative and quantitative methods for determining the
      type of contrast enhancement kinetic curve on DCE-MRI. MATERIALS AND METHODS:
      Ninety-six patients underwent breast DCE-MRI. The type of DCE-MRI kinetic curve
      was assessed qualitatively by three radiologists on two occasions. For
      quantitative assessment, the slope of the washout curve was calculated. Kappa
      statistics were used to determine inter- and intraobserver agreement for the
      qualitative method. Matched sample tables, the McNemar test, and receiver
      operating characteristic (ROC) curve statistics were used to compare quantitative
      versus qualitative methods for establishing or excluding malignancy. RESULTS:
      Seventy-eight lesions (77.2%) were malignant and 23 (22.8%) were benign. For the
      qualitative assessment, the intra- and interobserver agreement was good (kappa =
      0.76-0.88), with an area under the ROC curve (AUC) of 0.73-0.77. For the
      quantitative method, the highest AUC was 0.87, reflecting significantly higher
      diagnostic accuracies compared with qualitative assessment (p < 0.01 for the
      difference between the two methods). CONCLUSION: Quantitative assessment of the
      type of contrast enhancement kinetic curve on breast DCE-MRI resulted in
      significantly higher diagnostic performance for establishing or excluding
      malignancy compared with assessment based on the standard qualitative method.

PMID- 19770299
TI  - Diffusion-weighted MRI of advanced hepatocellular carcinoma during sorafenib
      treatment: initial results.
AB  - OBJECTIVE: The objective of our study was to evaluate signal changes of advanced
      hepatocellular carcinoma in diffusion-weighted MRI in the early-response
      monitoring of oral therapy with the multikinase inhibitor sorafenib. CONCLUSION:
      Hepatocellular carcinoma lesions exhibit characteristic but unusual apparent
      diffusion coefficient (ADC) changes during sorafenib therapy, consisting of early
      decrease in ADC after therapy onset followed by a reincrease. The ADC changes
      seem to reflect the underlying pathophysiologic mechanisms in tumor necrosis
      (most probably hemorrhagic) induced by this novel targeted agent early after
      therapy onset and may indicate tumor reactivation in the later follow-up period.

PMID- 19770300
TI  - MRI features of pancreatic colloid carcinoma.
AB  - OBJECTIVE: The purpose of our study was to retrospectively investigate the MRI
      findings (diameter, location, contour and margin, signal intensity
      characteristics, and enhancement patterns) in a series of eight patients with
      pathologically proven colloid carcinoma of the pancreas. CONCLUSION: Colloid
      carcinomas of the pancreas appear as masses with lobulating contours, indiscrete
      margins, and hyperintensity on T2-weighted images (n = 8). In addition, all
      patients who underwent dynamic studies (n = 4) showed peripheral and internal
      sponge-like or mesh-like progressive delayed contrast enhancement.

PMID- 19770301
TI  - CT-guided tube pericardiostomy: a safe and effective technique in the management
      of postsurgical pericardial effusion.
AB  - OBJECTIVE: The purpose of this study was to analyze the efficacy and examine the
      competitive cost of CT-guided tube pericardiostomy in the management of
      symptomatic postsurgical pericardial effusion. MATERIALS AND METHODS: Over a 4
      year period, 36 patients with symptomatic pericardial effusion were treated with
      CT-guided percutaneous placement of an indwelling pericardial catheter, for a
      total of 39 CT-guided tube pericardiostomy procedures. Thirty-three patients
      (92%) had undergone major cardiothoracic surgery, and three patients (8%) had
      undergone minimally invasive procedures. The medical records were retrospectively
      reviewed for clinical presentation, surgical history, imaging studies performed,
      procedural details, fluid characterization, and outcome. Charge comparison was
      performed with the American Medical Association Current Procedural Terminology
      codes and information acquired from the billing department at our facility.
      RESULTS: All 39 CT-guided tube pericardiostomy procedures were performed
      successfully without clinically significant complications. After 33 of the 39
      procedures (85%), symptoms did not recur after the catheter was removed. Three of
      36 patients (8%) had a recurrence of pericardial effusion. Comparison of
      procedure charges showed an 89% saving over intraoperative pericardial window
      procedures and no significant difference compared with ultrasound-guided tube
      pericardiostomy. Eight patients (21% of procedures) needed pleural drainage
      procedures, all of which were performed in the CT suite immediately after the
      tube pericardiostomy procedure. CONCLUSION: CT-guided tube pericardiostomy is a
      safe and effective alternative to surgical drainage in the care of patients with
      clinically significant pericardial effusion after cardiothoracic surgery and has
      the additional benefit of substantial cost savings.

PMID- 19770302
TI  - Relation between signal intensity on T2-weighted MR images and presence of
      microvascular obstruction in patients with acute myocardial infarction.
AB  - OBJECTIVE: In experimental animal models and human autopsy studies, hemorrhagic
      infarction caused by microvascular injury has been detected after coronary
      reperfusion. The purpose of this study was to determine whether detection of
      myocardial edema with T2-weighted MRI is influenced by the presence of
      microvascular obstruction. SUBJECTS AND METHODS: Thirty-seven patients underwent
      black-blood fat-suppressed T2-weighted, rest perfusion, and late gadolinium
      enhanced MRI 5.4 +/- 3.1 days after the onset of acute myocardial infarction. On
      T2-weighted MR images, the signal intensity in relation to that of remote
      myocardium was determined in the late gadolinium-enhanced and periinfarction
      areas. Segment-based analysis was performed to determine whether the presence of
      microvascular obstruction influences the detection of myocardial edema. RESULTS:
      The averaged signal intensity in the late gadolinium-enhanced area without
      microvascular obstruction was significantly higher than the signal intensity in
      remote normal myocardium (relative signal intensity, 1.83 +/- 0.50; p < 0.001).
      In contrast, the signal intensity in the microvascular obstruction area on T2
      weighted images was not significantly different from the signal intensity in
      remote myocardium (relative signal intensity, 1.14 +/- 0.26). The percentages of
      late gadolinium-enhanced segments with high signal intensity on T2-weighted MR
      images were 95% (73/77) without microvascular obstruction and 30% (22/73) with
      microvascular obstruction. CONCLUSION: With T2-weighted MRI, infarction
      associated edema can be reliably detected in infarct lesions without
      microvascular obstruction. Microvascular obstruction, however, does not
      necessarily exhibit high signal intensity on T2-weighted MRI. Careful attention
      is required in interpretation of cardiac MR images of patients who have
      experienced acute myocardial infarction and undergone percutaneous coronary
      intervention. The findings on T2-weighted MR images can be substantial
      underestimates of the extent of acute myocardial infarction.

PMID- 19770303
TI  - T2*-weighted and arterial spin labeling MRI of calf muscles in healthy volunteers
      and patients with chronic exertional compartment syndrome: preliminary
      experience.
AB  - OBJECTIVE: The purpose of our study was to assess temporal changes with exercise
      in T2* and arterial spin labeling signals in patients with chronic exertional
      compartment syndrome of the anterior compartment of the lower leg and in control
      subjects using T2* mapping and arterial spin labeling MRI. SUBJECTS AND METHODS:
      This prospective study was approved by the institutional research ethics board.
      Ten control subjects (five women and five men; mean age, 29.0 years) and nine
      patients with chronic exertional compartment syndrome (three women and six men;
      mean age, 33.7 years) gave informed written consent and underwent MRI of the calf
      muscles using an axial T2*-weighted multiecho gradient-recalled echo and a flow
      sensitive alternating inversion recovery sequence with echo-planar imaging
      readouts before (baseline) and 3, 6, 9, 12, and 15 minutes after exercise. T2*
      and arterial spin labeling signal changes (DeltaT2* and DeltaASL, respectively)
      over time were calculated relative to the baseline examination. DeltaT2* and
      DeltaASL between patients and control subjects were compared using the Student's
      t test. RESULTS: In both patients and control subjects, DeltaT2* and DeltaASL
      showed a peak at 3 minutes after exercise, followed by a decrease over time. The
      maximum DeltaT2* was 26% and 29% for patients and control subjects, respectively.
      The maximum DeltaASL was 183% and 224% for patients and control subjects,
      respectively. After 15 minutes, arterial spin labeling signal returned to
      baseline; however, T2* remained elevated (8% in patients; 10% in control
      subjects). No statistically significant differences between patients and control
      subjects in postexercise DeltaT2* and DeltaASL were found (p = 0.21-0.98).
      CONCLUSION: After calf muscle exercise, no statistically significant differences
      in T2* relaxation times or arterial spin labeling signal, indicative of
      differences in muscle oxygenation and perfusion status, were found between
      patients with chronic exertional compartment syndrome and control subjects.

PMID- 19770304
TI  - Anterior ankle impingement and talar bony outgrowths: osteophyte or enthesophyte?
      Paleopathologic and cadaveric study with imaging correlation.
AB  - OBJECTIVE: Bony "spurs" are a major component of anterior ankle impingement
      syndrome. The two major accepted hypotheses on the origin of these bony spurs are
      osteophyte formation due to repetitive microtrauma and enthesophyte development
      because of recurrent capsular or ligamentous traction. The purpose of this study
      was to provide a detailed evaluation of the bony outgrowths that arise on the
      anterior aspect of the talus and correlate them with the sites of capsular
      attachment. MATERIALS AND METHODS: Twenty-eight well-preserved talus bones from
      the San Diego Museum of Man were assessed regarding the presence of outgrowths on
      the anterior aspect of the talus. The distance of the outgrowths from the talar
      head was measured. The results were correlated with measurements of capsular
      attachment on the anterior aspect of the talus derived from MR arthrographic
      images in 13 cadaveric ankles. RESULTS: The average distance of capsular
      attachment from the talar head in the medial aspect of the bone was 10.63 mm and
      in the lateral part was 12.04 mm. The mean distance of bony spurs from the talar
      head in the medial and lateral parts of the talus was 17.2 and 12.5 mm,
      respectively. Medially, the talar spurs developed more proximally on the neck
      compared to the capsular attachment (p < 0.01). Laterally, this difference was
      not significant (p = 0.26). CONCLUSION: On the medial part of the anterior talus,
      bone development appears to occur in an intraarticular location (i.e.,
      osteophytes). Laterally, the outgrowths develop extraarticularly and appear to
      result from capsular and ligamentous traction (i.e., enthesophytes).

PMID- 19770305
TI  - Accuracy of cross-table lateral knee radiography for evaluation of joint
      effusions.
AB  - OBJECTIVE: The purpose of our study was to investigate the efficacy of cross
      table lateral knee radiography in the diagnosis of knee effusions compared with
      an MRI reference standard, to evaluate reader experience in effusion assessment,
      and to establish a new threshold for suprapatellar pouch measurement for the
      diagnosis of effusion. MATERIALS AND METHODS: First- and third-year radiology
      residents and an attending musculoskeletal radiologist retrospectively assessed
      108 cross-table lateral knee radiographs for qualitative grading of joint fluid
      and quantitative measurement of the suprapatellar pouch. Qualitative and
      quantitative evaluation of ipsilateral knee MRI examinations performed within 1
      week of radiography was performed by two attending musculoskeletal radiologists
      as a reference standard. RESULTS: Qualitative visual grading of cross-table
      lateral radiographs had a sensitivity of 90-92%, specificity of 39-54%, and
      accuracy of 69-76% for joint effusion. Extrapolating from previous work showing 4
      mL of fluid distends the suprapatellar pouch to 4 mm on midline sagittal MRI, the
      corresponding measurement on cross-table lateral radiographs was predicted to be
      7 mm. Using this new criterion of effusion, sensitivity, specificity, and
      accuracy compared with an MR midline sagittal reference standard were 76%, 83%,
      and 81%, respectively. Historical data for overhead lateral radiographs had a
      sensitivity of 78%, specificity of 80%, and accuracy of 79%. CONCLUSION:
      Qualitative visual assessment of cross-table lateral knee radiographs is highly
      sensitive for the detection of joint effusion. By performing quantitative
      evaluation with a new 7-mm criterion for suprapatellar pouch measurement,
      sensitivity, specificity, and accuracy are equivalent to that of overhead lateral
      radiography.

PMID- 19770306
TI  - Lymphocytic thyroiditis on fine-needle aspiration biopsy of focal thyroid
      nodules: approach to management.
AB  - OBJECTIVE: The purpose of this study was to determine the optimal management
      strategy for thyroid nodules diagnosed as lymphocytic thyroiditis on sonography
      guided fine-needle aspiration biopsy (FNAB) of focal thyroid nodules. MATERIALS
      AND METHODS: One hundred eleven patients were included in this study: among 45
      patients with follow-up sonography-guided FNAB, 21 underwent follow-up sonography
      more than 12 months after the initial sonography and 24 were followed up with
      sonography and sonography-guided FNAB within 12 months. Among 45 patients with
      follow-up sonography-guided FNAB, seven underwent thyroid surgery. Follow-up
      sonography results and cytopathologic results were used as reference standards.
      RESULTS: There were no malignancies among 71 probably benign lesions on initial
      sonography. In contrast, of the 40 lesions that were suspicious malignant on
      sonography, eight proved to be papillary thyroid carcinoma on follow-up
      sonography-guided FNAB and histopathology. CONCLUSION: Lymphocytic thyroiditis
      can show variable features on sonography. When a nodule shows probably benign
      features on sonography, follow-up with sonography is sufficient. However, if a
      nodule shows suspicious malignant features on sonography and shows no change or
      increase in size on follow-up examination, follow-up sonography-guided FNAB
      should be performed.

PMID- 19770307
TI  - Free gadolinium is a likely trigger of nephrogenic systemic fibrosis.

PMID- 19770308
TI  - Achilles Wiitis: making the case for proprioceptive training in tendinopathy.

PMID- 19770309
TI  - Accurate nomenclature of the veins of the lower extremities.

PMID- 19770310
TI  - Pharmacokinetics of (99m)Tc-MAG3.

PMID- 19770311
TI  - Interventional radiology: an ever-changing landscape.

PMID- 19770312
TI  - Deep venous thrombosis: the opportunity at hand.
AB  - OBJECTIVE: The use of imaging-guided treatments for deep venous thrombosis (DVT)
      is accelerating. Increased appreciation of the impact of postthrombotic syndrome
      on DVT patients' quality of life and advances in thrombolytic methods have
      together sparked an unprecedented degree of interdisciplinary collaboration in
      developing contemporary DVT treatment guidelines and a pivotal clinical trial to
      establish the risk-benefit ratio of interventional DVT therapy. CONCLUSION:
      Radiologists should improve their DVT education, support ongoing clinical trials,
      and collaborate with DVT-focused nonradiologists in their institutions.

PMID- 19770313
TI  - CT and MRI in diseases of the aorta.
AB  - OBJECTIVE: This review focuses on the role of CT and MRI in the diagnosis, follow
      up, and surgical planning of aortic aneurysms and acute aortic syndromes,
      including aortic dissection, intramural hematoma, and penetrating aortic ulcer.
      It also provides a systematic approach to the definition, causes, natural
      history, and imaging principles of these diseases. CONCLUSION: An understanding
      of the pathophysiology, natural history, and imaging features is the key to
      successful diagnosis and appropriate management of patients with these aortic
      diseases.

PMID- 19770314
TI  - Liver metastases of neuroendocrine tumors: treatment with hepatic transarterial
      chemotherapy using two therapeutic protocols.
AB  - OBJECTIVE: The objective of our study was to retrospectively determine the
      effectiveness of hepatic transarterial chemotherapy using two therapeutic
      protocols-mitomycin C alone and combined mitomycin C and gemcitabine-on local
      tumor control and survival rate in patients with liver metastases from
      neuroendocrine tumors. MATERIALS AND METHODS: This article describes a
      retrospective study of 48 patients (age range, 37-77 years; mean age, 61.1 years;
      SD, 10.3) with liver metastases from neuroendocrine tumors who underwent
      repetitive selective hepatic artery chemotherapy using mitomycin C alone (group
      1, n = 18 patients who underwent 182 therapeutic sessions; mean, 10.11 sessions
      per patient) and combined mitomycin C and gemcitabine chemotherapy agents (group
      2, n = 30 patients who underwent 312 therapeutic sessions; mean, 10.4 sessions
      per patient) with 4-week intervals between treatment sessions. RESULTS: Both
      treatment protocols were well tolerated by all patients. Only minor side effects
      occurred in both groups, and no major complications developed. Local tumor
      control evaluation according to the Response Evaluation Criteria in Solid Tumors
      (RECIST) revealed the following for group 1: partial response, 11.1%; stable
      disease, 50%; and progressive disease, 38.9%. RECIST criteria for group 2
      indicated partial response in 23.33%, stable disease in 53.34%, and progressive
      disease in 23.33%. The survival rate from the initial diagnosis to the fifth year
      for group 1 was 11.11% and for group 2, 46.67%. The median survival time from the
      initial diagnosis of group 1 was 38.67 months, whereas in group 2 it was 57.1
      months. CONCLUSION: Transarterial hepatic chemotherapy using mitomycin C and
      gemcitabine can be an effective therapeutic protocol for controlling local
      metastases and improving survival time in patients with hepatic metastases from
      neuroendocrine tumors.

PMID- 19770315
TI  - Hepatocellular carcinoma with cirrhosis: are patients with neoplastic main portal
      vein invasion eligible for percutaneous radiofrequency ablation of both the
      nodule and the portal venous tumor thrombus?
AB  - OBJECTIVE: The purpose of this study was to examine the results of percutaneous
      radiofrequency ablation of both medium-sized hepatocellular carcinoma (HCC) and
      the accompanying main portal venous tumor thrombus in patients with cirrhosis.
      SUBJECTS AND METHODS: From January 2005 to January 2008, among 1,837
      consecutively registered patients with HCC seen at our institution, 412 had HCC
      and portal venous invasion; 27 of the 412 had a single HCC nodule accompanied by
      main portal venous tumor thrombus. Thirteen patients (10 men, three women; mean
      age, 70 years; range, 66-74 years) with 13 HCC nodules 3.7-5 cm in diameter
      extending into the main portal trunk underwent percutaneous radiofrequency
      ablation. Fourteen matched patients (10 men, four women; mean age, 69 years;
      range, 67-73 years) with 14 HCC nodules 3.6-4.8 cm in diameter extending into the
      main portal trunk refused radiofrequency ablation and composed the control group.
      Diagnosis of main portal venous tumor thrombus was made with fine-needle biopsy
      in all cases. Radiofrequency ablation was performed first on the main portal
      venous tumor thrombus and then on the HCC nodule. Efficacy of radiofrequency was
      defined as complete necrosis of HCC and complete recanalization of the main
      portal trunk and its branches. HCC necrosis was evaluated with enhanced CT.
      Recanalization of portal vessels was analyzed with color Doppler and contrast
      enhanced ultrasound. Radiofrequency ablation was performed under ultrasound
      guidance with a perfused needle electrode. RESULTS: Complete necrosis of the HCC
      associated with complete recanalization of the main portal vein and its branches
      was achieved in 10 patients (efficacy, 77%). In the other three patients,
      necrosis of the HCC ranged from 70% to 90%, and recanalization of the main portal
      trunk was not complete. No major complications occurred. In three cases, mild to
      moderate ascites and increased aspartate aminotransferase and alanine
      aminotransferase levels were found. The follow-up periods ranged from 3 to 36
      months among the treated patients and 2 to 10 months among the untreated
      patients. The cumulative survival rate was 77% 6, 12, and 36 months after
      procedure in the treated group and 43% and 0% 6 and 12 months after diagnosis in
      the untreated group (p < 0.0001). All 10 successfully treated patients were alive
      and the portal system was patent at the end of the follow-up period. All three
      untreated patients died of progressive disease within 5 months of diagnosis.
      CONCLUSION: Radiofrequency ablation can destroy both single intraparenchymal
      medium-sized HCCs and the accompanying main portal venous tumor thrombus with
      high efficacy and safety and a low rate of complications.

PMID- 19770316
TI  - Prospective and retrospective ECG gating for thoracic CT angiography: a
      comparative study.
AB  - OBJECTIVE: The objective of our study was to compare radiation dose, contrast
      load, thoracic aortic attenuation value, and image quality parameters of MDCT
      thoracic aortography performed with prospective and retrospective cardiac gating.
      MATERIALS AND METHODS: Studies were performed on 80 patients (prospective ECG
      gating, n = 40; retrospective ECG gating, n = 40) either being evaluated for
      thoracic aortic aneurysm (n = 23) or aortic dissection (n = 36) or undergoing
      postsurgical or postintervention follow-up (n = 21). Image acquisition parameters
      and radiation dose (CT dose index volume [CTDI(vol)] and dose-length product
      [DLP]) were obtained from image archival data. Contrast load and aortic
      attenuation values were obtained from a data registry. The comparative degrees of
      motion artifact and banding artifact were assessed on parasagittal maximum
      intensity-projection (MIP) images and reformatted images in the plane of the
      aortic valve. RESULTS: CTDI(vol) and DLP in the prospective ECG-gating group was
      28.8 +/- 2.12 mGy (mean +/- SD) and 833.7 +/- 115.77 mGy/cm, respectively, which
      are significantly lower (p < 0.001) than those values in the retrospective ECG
      gating group (74.7 +/- 13.42 mGy and 2,547.3 +/- 553.27 mGy/cm). The average
      contrast load in the prospective gating group was 109.1 +/- 14.74 mL and in the
      retrospective gating group, 101.3 +/- 10.45 mL (p < 0.05). The average aortic
      attenuation values (in Hounsfield units) for the prospective and retrospective
      ECG-gated groups were 447.6 and 350.2 HU, respectively, for the mid ascending
      aorta, 413.6 and 325.7 HU for the mid aortic arch, 418.2 and 327.6 HU for the mid
      descending aorta, and 355.0 and 306.2 HU for the supraceliac aorta. Subjective
      scores of motion artifact and banding artifact were equivalent between the two
      groups. CONCLUSION: Compared with retrospective ECG-gated thoracic CT
      angiography, prospective ECG-gated thoracic CT angiography was associated with a
      lower radiation dose, slightly increased contrast load, increased aortic
      attenuation values, and equivalent image quality.

PMID- 19770317
TI  - Percutaneous radiofrequency ablation of hepatocellular carcinoma in 14 patients
      undergoing regular hemodialysis for end-stage renal disease.
AB  - OBJECTIVE: Management of hepatocellular carcinoma is a major problem in the care
      of patients undergoing regular hemodialysis treatments, mainly because of a high
      prevalence of hepatitis C virus infection. The purpose of this study was
      retrospective assessment of the safety and efficacy of percutaneous
      radiofrequency ablation of hepatocellular carcinoma in the care of patients with
      end-stage renal disease undergoing regular hemodialysis treatments. MATERIALS AND
      METHODS: Between October 2004 and June 2008, 14 carefully selected hemodialysis
      patients with hepatocellular carcinoma (five naive, nine recurrent) underwent a
      total of 19 radiofrequency ablation treatments. An internally cooled or
      expandable electrode was used. After tumor ablation, the insertion site at the
      liver surface was subjected to additional ablation to reduce the bleeding risk.
      RESULTS: The Child-Pugh score was 6 or better in all patients but one. The number
      of tumors was one or two, and the tumor diameter was 35 mm or less in all
      treatments. No complication such as intraperitoneal hemorrhage was found in any
      treatment. Local tumor progression was found after one treatment and was
      successfully managed with subsequent radiofrequency ablation. During the mean
      observation period of 343 days, there was only one death, of heart failure, among
      the five patients with naive tumors. CONCLUSION: The safety and effectiveness of
      radiofrequency ablation were not compromised in this series of selected patients
      with hepatocellular carcinoma who were undergoing hemodialysis. Radiofrequency
      ablation is a promising option for small hepatocellular carcinomas in patients
      undergoing regular hemodialysis treatments.

PMID- 19770318
TI  - Modifying peripheral IV catheters with side holes and side slits results in
      favorable changes in fluid dynamic properties during the injection of iodinated
      contrast material.
AB  - OBJECTIVE: The purpose of this study was to compare a standard peripheral end
      hole angiocatheter with those modified with side holes or side slits using
      experimental optical techniques to qualitatively compare the contrast material
      exit jets and using numeric techniques to provide flow visualization and
      quantitative comparisons. MATERIALS AND METHODS: A Schlieren imaging system was
      used to visualize the angiocatheter exit jet fluid dynamics at two different flow
      rates. Catheters were modified by drilling through-and-through side holes or by
      cutting slits into the catheters. A commercial computational fluid dynamics
      package was used to calculate numeric results for various vessel diameters and
      catheter orientations. RESULTS: Experimental images showed that modifying
      standard peripheral IV angiocatheters with side holes or side slits qualitatively
      changed the overall flow field and caused the exiting jet to become less well
      defined. Numeric calculations showed that the addition of side holes or slits
      resulted in a 9-30% reduction of the velocity of contrast material exiting the
      end hole of the angiocatheter. With the catheter tip directed obliquely to the
      wall, the maximum wall shear stress was always highest for the unmodified
      catheter and was always lowest for the four-side-slit catheter. CONCLUSION:
      Modified angiocatheters may have the potential to reduce extravasation events in
      patients by reducing vessel wall shear stress.

PMID- 19770319
TI  - Digital subtraction angiography-guided percutaneous transcatheter foam
      sclerotherapy of varicocele: a novel tracking technique.
AB  - OBJECTIVE: The purpose of this article is to describe a new tracking technique
      for using sclerosing foam with radiologic guidance. Thirty-nine men with
      varicocele underwent transcatheter foam sclerotherapy. Sclerosing foam was
      produced by the Tessari technique using 5% sodium morrhuate solution, and foam
      sclerotherapy was performed by the new tracking technique, the filling-defects
      technique, under digital subtraction angiography (DSA) guidance using a step-by
      step process consisting of spermatic phlebography, injection of sclerosing foam
      as a negative radiographic contrast material, and rinse of the catheter.
      CONCLUSION: The DSA-guided filling-defects technique is a feasible method for
      tracking the sclerosing foam and should be used in the treatment of other venous
      disorders when using sclerosing foam with radiologic guidance.

PMID- 19770320
TI  - Is breast MRI helpful in the evaluation of inconclusive mammographic findings?
AB  - OBJECTIVE: The purpose of this study was to evaluate the usefulness of MRI of the
      breast in cases in which mammographic or sonographic findings are inconclusive.
      MATERIALS AND METHODS: We retrospectively reviewed images from 115 MRI
      examinations of the breast performed from 1999 to 2005 for the indication of
      problem-solving for inconclusive findings on a mammogram. Forty-eight of the 115
      women (41.8%) were at high risk. We discerned whether sonography or MRI was used
      as an adjunctive tool and correlated the findings with those in the pathology
      database. RESULTS: The equivocal findings most frequently leading to MRI were
      asymmetry and architectural distortion. No suspicious MRI correlate was found in
      100 of 115 cases (87%). These cases were found stable at follow-up mammography or
      MRI after a mean of 34 months. Fifteen enhancing masses (13%) that corresponded
      to the mammographic abnormality were seen on MR images. All masses identified at
      MRI were accurately localized for biopsy, and six malignant lesions were
      identified. Four of six malignant tumors were seen in one mammographic view only;
      two were seen on second-look ultrasound images. MRI had a sensitivity of 100% and
      compared with mammography had significantly higher specificity (91.7% vs 80.7%, p
      = 0.029), positive predictive value (40% vs 8.7%, p = 0.032), and overall
      accuracy (92.2% vs 78.3%, p = 0.0052). Eighteen incidental lesions (15.7%) were
      detected at MRI, and all were subsequently found benign. CONCLUSION: We found
      breast MRI to be a useful adjunctive tool when findings at conventional imaging
      were equivocal. Strict patient selection criteria should be used because of the
      high frequency of incidental lesions seen on MR images.

PMID- 19770321
TI  - BI-RADS lesion characteristics predict likelihood of malignancy in breast MRI for
      masses but not for nonmasslike enhancement.
AB  - OBJECTIVE: The purpose of our study was to evaluate the predictive features of BI
      RADS lesion characteristics and the risk of malignancy for mammographically and
      clinically occult lesions detected initially on breast MRI. MATERIALS AND
      METHODS: We reviewed 1,523 consecutive breast MRI examinations performed from
      January 1, 2003, to June 30, 2005, to identify all lesions initially detected on
      MRI and assessed as BI-RADS 4 or 5 for which the patient underwent subsequent
      imaging-guided needle or excisional biopsy. BI-RADS lesion features were recorded
      for each case, and the risk of malignancy was assessed using generalized
      estimating equations. Separate multivariate models were constructed for lesions
      classified as masses. RESULTS: Included in the analysis were 258 suspicious
      lesions in 196 women. Among all lesions, those of 1 cm or greater were
      significantly more often malignant (50/147, 34%) than lesions of less than 1 cm
      (22/111, 20%; odds ratio, 2.09; 95% CI, 1.13-3.83). For masses, size, BI-RADS
      margin, and enhancement pattern predicted malignancy. In multivariate analysis of
      combinations of features, masses of 1 cm or greater with heterogeneous
      enhancement and irregular margins had a 68% probability of malignancy. Masses of
      1 cm or greater with smooth margins and homogeneous enhancement had the lowest
      predicted probability of malignancy of 3%. BI-RADS descriptors and size were not
      significant predictors of malignancy for nonmasslike enhancement (NMLE).
      CONCLUSION: Combinations of BI-RADS lesion descriptors can predict the
      probability of malignancy for breast MRI masses but not for NMLE. If our model is
      validated, masses with a low probability of malignancy may be eligible for short
      interval follow-up rather than biopsy. Further research focused on predictive
      features of NMLE is needed.

PMID- 19770322
TI  - Radioguided localization of nonpalpable breast cancer lesions: randomized
      comparison with wire localization in patients undergoing conservative surgery and
      sentinel node biopsy.
AB  - OBJECTIVE: The aim of this investigation was to determine whether radioguided
      occult lesion localization and routine wire localization differ in respect to the
      effectiveness of complete excision of nonpalpable breast cancer lesions. SUBJECTS
      AND METHODS: This prospective randomized study included patients with breast
      cancer scheduled for conservative tumor excision and sentinel node biopsy.
      Patients were randomized to either radioguided localization or wire localization.
      Comparative radiologic, surgical, and pathologic data were collected and analyzed
      to establish the duration, ease of use, and accuracy of the two techniques for
      occult lesion localization. The effectiveness of sentinel node biopsy also was
      assessed. One radiologist and two surgeons participated in the study. RESULTS:
      Among 134 patients, 68 were treated with wire localization and 66 with
      radioguided localization. The mean duration of radiologic localization was
      significantly shorter for radioguided localization (p < 0.001). No statistical
      differences were found for the other parameters studied. Radiography of the
      surgical specimen showed 100% lesion excision with both techniques. Complete
      tumor excision with tumor-free margins was achieved in 89.4% of patients who
      underwent radioguided localization group and 82.4% of patients who underwent wire
      localization. Pathologic examination showed the excised tissue volume was
      slightly larger (p = 0.371) and lesion concentricity slightly less (p = 0.730)
      with radioguided localization. The sentinel node detection rate was 91% with
      radioguided localization and 84% with wire localization. CONCLUSION: The
      radioguided technique is as effective as the standard wire technique for
      localization and excision of nonpalpable breast cancer lesions and is somewhat
      faster and simpler to perform than wire localization.

PMID- 19770323
TI  - Comparison of digital mammography and screen-film mammography in breast cancer
      screening: a review in the Irish breast screening program.
AB  - OBJECTIVE: Clinical trials to date into the use of full-field digital mammography
      (FFDM) for breast cancer screening have shown variable results. The aim of this
      study was to review the use of FFDM in a population-based breast cancer screening
      program and to compare the results with screen-film mammography. MATERIALS AND
      METHODS: The study included 188,823 screening examinations of women between 50
      and 64 years old; 35,204 (18.6%) mammograms were obtained using FFDM. All films
      were double read using a 5-point rating scale to indicate the probability of
      cancer. Patients with positive scores were recalled for further workup. The
      recall rate, cancer detection rate, and positive predictive value (PPV) of FFDM
      were compared with screen-film mammography. RESULTS: The cancer detection rate
      was significantly higher for FFDM than screen-film mammography (6.3 vs 5.2 per
      1,000, respectively; p = 0.01). The cancer detection rate for FFDM was higher
      than screen-film mammography for initial screening and subsequent screening, for
      invasive cancer and ductal carcinoma in situ, and across all age groups. The
      cancer detection rate for cancers presenting as microcalcifications was
      significantly higher for FFDM than for screen-film mammography (1.9 vs 1.3 per
      1,000, p = 0.01). The recall rate was significantly higher for FFDM than screen
      film mammography (4.0% vs 3.1%, p < 0.001). There was no significant difference
      in the PPVs of recall to assessment for FFDM and screen-film mammography (15.7%
      and 16.7%, p = 0.383). CONCLUSION: FFDM resulted in significantly higher cancer
      detection and recall rates than screen-film mammography in women 50-64 years old.
      The PPVs of FFDM and screen-film mammography were comparable. The results of this
      study suggest that FFDM can be safely implemented in breast cancer screening
      programs.

PMID- 19770324
TI  - Early first trimester fetal dose estimation method in a multivendor study of 16-
      and 64-MDCT scanners and low-dose imaging protocols.
AB  - OBJECTIVE: The purpose of this study was to corroborate the relation between the
      estimated absorbed fetal dose derived from directly measured uterine doses early
      in the first trimester and the volume CT dose index (CTDI(vol)) for 16- and 64
      MDCT of the maternal chest, abdomen, and pelvis. MATERIALS AND METHODS: Estimated
      absorbed fetal dose was measured with a metal oxide semiconductor field effect
      transistor (MOSFET) dosimeter placed in the expected uterine location in an
      anthropomorphic phantom of a woman and scanned with 16- and 64-MDCT units of one
      vendor and a 64-MDCT unit of another vendor. A trauma chest, abdomen, and pelvis
      protocol and an abdomen and pelvis protocol were used. Absorbed uterine dose was
      measured directly from the MOSFET detector. The CTDI(vol) for each protocol was
      recorded from the scanner console. Correlation between mean uterine dose and
      CTDI(vol) was tested with a goodness of fit model. RESULTS: The absorbed uterine
      dose ranged from 9.25 to 37.7 mGy. Absorbed fetal dose in the early first
      trimester correlated with CTDI(vol) in a linear regression equation. For the 16
      MDCT scanner, at 130 kVp, the fetal dose was 2.091 x CTDI(vol) - 9.489. For the
      64-MDCT scanner from the same vendor, at 120 kVp, the fetal dose was 1.113 x
      CTDI(vol) + 1.773. For the 64-MDCT scanner from the other vendor, at 120 kVp, the
      fetal dose was 1.378 x CTDI(vol) - 1.014. The goodness of fit results (R(2)) for
      the equations were 0.97, 0.98, and 0.99. CONCLUSION: Estimated absorbed fetal
      dose during the first trimester of pregnancy is linearly associated with
      CTDI(vol) regardless of beam energy, detector configuration, and scanner
      manufacturer.

PMID- 19770325
TI  - Targeted ultrasound of the breast in women with abnormal MRI findings for whom
      biopsy has been recommended.
AB  - OBJECTIVE: This study was performed to identify characteristics of suspicious
      lesions seen on breast MRI that are most likely to have an ultrasound correlate
      and to determine how often the presumed ultrasound correlate actually corresponds
      to the MRI finding. MATERIALS AND METHODS: From September 2005 through December
      2007, targeted ultrasound was performed for 519 suspicious MRI-detected lesions
      in 361 women. Retrospective review was performed to determine lesion type (mass
      vs nonmass), lesion descriptors, lesion size, BI-RADS category, indication for MR
      examination, patient age, and biopsy outcome. The results of 80 follow-up MRI
      examinations among 154 cases with concordant benign results on ultrasound-guided
      biopsy were noted. RESULTS: A presumed ultrasound correlate was found in 290
      (56%) of the 519 lesions with masses more likely than nonmass lesions to be seen
      with ultrasound (62% of masses and 31% of nonmass lesions). Increasing lesion
      size, assessment of BI-RADS category 5 versus BI-RADS category 4, rim enhancement
      in masses, and clumped enhancement in nonmass lesions were also significantly
      more likely to have an ultrasound correlate. On follow-up imaging in 80 benign,
      concordant ultrasound-guided biopsies, the sonographic lesion did not correspond
      to the MRI finding in 10. Nine of these 10 lesions underwent subsequent MRI
      guided biopsy and five cancers were diagnosed. CONCLUSION: The MR characteristics
      of lesions most likely to be seen with an ultrasound correlate were mass versus
      nonmass, increasing size, and increased level of suspicion of the lesion. Clip
      placement and follow-up imaging after ultrasound-guided biopsy that yields benign
      concordant results should be performed to detect cases in which the presumed
      ultrasound correlate is inaccurate to detect unsuspected false-negative biopsies.

PMID- 19770326
TI  - Assessment of breast lesions with diffusion-weighted MRI: comparing the use of
      different b values.
AB  - OBJECTIVE: Our purpose was to study the utility of diffusion-weighted MRI in
      differentiating benign from malignant breast lesions by assessing the best b
      values. SUBJECTS AND METHODS: Forty-five women (mean age, 46.1 years) with 52
      focal mass breast lesions underwent diffusion-weighted imaging with different b
      values. The apparent diffusion coefficient (ADC) value of each lesion was
      calculated from the ADC maps done using five b values (0, 250, 500, 750, and
      1,000 s/mm(2)) and using b values of 0 s/mm(2) with each other b value separately
      (0 and 250 s/mm(2), 0 and 500 s/mm(2), 0 and 750 s/mm(2), 0 and 1,000 s/mm(2)).
      The mean ADC values were correlated with imaging findings and histopathologic
      diagnoses. The cutoff ADC value, sensitivity, and specificity of diffusion
      weighted imaging to differentiate benign and malignant lesions were calculated in
      all b value combinations. A p value of < 0.05 was considered statistically
      significant. RESULTS: The mean ADC value was significantly lower for malignant
      lesions compared to benign lesions (p < 0.0001) in all b value combinations. No
      statistical difference was seen between the ADC obtained from different b value
      combinations (p = 0.2581) in the differentiation between benign and malignant
      lesions. The ADC calculated from b 0 and 750 s/mm(2) was slightly better than the
      other b value combinations, showing a sensitivity of 92.3% and a specificity of
      96.2%. CONCLUSION: Diffusion-weighted imaging is a potential resource as a
      coadjutant of MRI in the differentiation between benign and malignant lesions.
      Such imaging can be performed without a significant increase in examination time,
      especially because it can be done with lower b values.

PMID- 19770327
TI  - B-mode ultrasound with algorithm based on statistical analysis of signals:
      evaluation of liver fibrosis in patients with chronic hepatitis C.
AB  - OBJECTIVE: The purpose of this study was to evaluate the degree of liver fibrosis
      in patients with chronic hepatitis C by use of a method in which the homogeneity
      of the tissue texture of the liver on B-mode ultrasound images is analyzed on the
      basis of results of a statistical chi-square test of the echo amplitudes. The
      method includes an algorithm for removing small structures, such as cross
      sections of the thin vessels, in the background texture to minimize differences
      in analysis results between users. SUBJECTS AND METHODS: Analysis was performed
      on images of 148 patients with histologically proven chronic hepatitis C without
      cirrhosis. The peak value of the C(m)(2) (modified chi-square distribution)
      histogram was calculated from B-mode ultrasound images, and the resulting value
      was compared with the histologic fibrosis grade. RESULTS: The peak C(m)(2)
      histogram value for grade F3 fibrosis was higher than that for grades F0 and F1
      (p < 0.0001) and F2 (p = 0.0003). The value for grade F2 was higher than that for
      grades F0 and F1 (p = 0.0027). The values gradually increased with an increase in
      liver fibrosis grade, although no difference was found between grades F0 and F1.
      CONCLUSION: The grades of liver fibrosis in patients with chronic hepatitis C are
      well discriminated with the B-mode ultrasound-based analysis algorithm without
      discrimination between grades F0 and F1. Findings on conventional ultrasound
      images may reflect progression of liver fibrosis even in the absence of
      cirrhosis.

PMID- 19770328
TI  - Assessment of tumor necrosis of hepatocellular carcinoma after chemoembolization:
      diffusion-weighted and contrast-enhanced MRI with histopathologic correlation of
      the explanted liver.
AB  - OBJECTIVE: The purpose of this study was to compare, with histopathologic
      examination of the liver explant as the reference standard, diffusion-weighted
      MRI with contrast-enhanced subtraction MRI in the assessment of necrosis of
      hepatocellular carcinoma (HCC) after trans arterial chemoembolization (TACE).
      MATERIALS AND METHODS: The cases of 21 patients with HCC who underwent MRI after
      TACE were evaluated. Two independent observers calculated the apparent diffusion
      coefficient (ADC) of HCC and measured percentage tumor necrosis on subtraction
      images. The ADCs of necrotic and viable tumor tissues were compared. ADC and
      percentage necrosis on subtraction images were correlated with percentage
      necrosis found at pathologic examination. Receiver operating characteristics
      analysis was performed on the diagnosis of complete tumor necrosis. RESULTS:
      Twenty-eight HCCs (mean diameter, 2.3 cm) were evaluated. There were significant
      differences between the ADC of viable tissue and that of necrotic tumor tissue
      (1.33 +/- 0.41 vs 2.04 +/- 0.38 x 10(-3) mm(2)/s, p < 0.0001). There was
      significant moderate correlation between ADC and the pathologic finding of
      percentage necrosis (r = 0.64, p < 0.001) and significant strong correlation
      between subtraction image and pathologic percentage necrosis (r = 0.89-0.91,
      depending on the phase; p < 0.001). In the diagnosis of complete tumor necrosis,
      ADC had an area under the curve, sensitivity, and specificity of 0.85, 75%, and
      87.5% compared with 0.82-0.89, 100%, and 58.3-79.1% for subtraction imaging (p >
      0.5 between ADC and subtraction imaging). CONCLUSION: Compared with diffusion
      weighted imaging, contrast-enhanced MRI with subtraction technique had more
      significant correlation with the histopathologic findings in the evaluation of
      necrosis of HCC after TACE. There was no difference, however, between the two
      methods in diagnosis of complete tumor necrosis.

PMID- 19770329
TI  - Qualitative and quantitative evaluation of hepatocellular carcinoma and cirrhotic
      liver enhancement using Gd-EOB-DTPA.
AB  - OBJECTIVE: The objective of our study was to prospectively evaluate
      quantitatively and qualitatively the enhancement patterns of cirrhotic liver
      tissue and hepatocellular carcinoma (HCC) after administration of the hepatocyte
      specific contrast agent gadolinium ethoxybenzyl diethylenetriamine pentaacetic
      acid (Gd-EOB-DTPA) on dynamic MRI and to determine the time point of maximum
      liver-to-lesion contrast. SUBJECTS AND METHODS: Twenty-five patients with HCC in
      liver cirrhosis underwent 1.5-T MRI. T2-weighted turbo spin-echo and T1-weighted
      3D gradient-echo sequences before and between 15 seconds and 20 minutes after the
      injection of 10 mL of Gd-EOB-DTPA were performed. Signal-to-noise ratios (SNRs)
      of liver parenchyma and liver-to-lesion contrast-to-noise ratios (CNRs) were
      calculated and plotted over time. Enhancement patterns of HCC were characterized
      qualitatively by two radiologists. RESULTS: The SNR of liver parenchyma increased
      significantly at 15 seconds and 60 seconds after contrast injection and remained
      stable thereafter. HCC showed positive CNR during the arterial phase and
      increasingly negative CNR during the further time course (p < 0.05). The maximum
      absolute CNR was found at 20 minutes after contrast injection. There was no
      correlation between the degree of enhancement at any time point and tumor grade.
      On qualitative evaluation, 16 HCCs showed arterial enhancement with early
      washout, and five showed arterial enhancement with late washout. In the remaining
      four HCCs, enhancement persisted until 20 minutes. Lesion conspicuity at 20
      minutes after contrast injection was at least equal to or higher than it was on
      the remaining sequences in 19 of the 25 patients. CONCLUSION: After Gd-EOB-DTPA
      injection, most HCCs showed typical arterial enhancement with early washout.
      Liver-to-lesion contrast was best at 20 minutes.

PMID- 19770330
TI  - Differential CT features of intraductal biliary metastasis and double primary
      intraductal polypoid cholangiocarcinoma in patients with a history of
      extrabiliary malignancy.
AB  - OBJECTIVE: The purpose of this study was to discern clinical and imaging features
      for differentiating intraductal metastasis from double primary intraductal
      cholangiocarcinoma in patients with a history of extrabiliary malignant disease.
      MATERIALS AND METHODS: Over a 10-year period, the cases of 14 patients with
      histopathologically proven intraductal metastasis (n = 8) or double primary
      intraductal cholangiocarcinoma (n = 6) who had a history of extrabiliary
      malignancy were identified. Two radiologists retrospectively reviewed CT (n = 14)
      and MR (n = 6) images for the size and appearance of the intraductal lesion,
      presence of a parenchymal mass, multiplicity, attenuation on arterial and portal
      phase images, and presence of calcification. Clinical findings such as the
      location of extrabiliary malignancy and presence of Clonorchis sinensis
      infestation also were recorded. Univariate tests were used to differentiate the
      two disease entities. RESULTS: Histopathologic confirmation was obtained by
      surgical resection (n = 12) or ultrasound-guided biopsy (n = 2). All intraductal
      metastatic lesions were of colorectal cancer, and all intraductal
      cholangiocarcinomas were associated with extracolonic malignant disease,
      including three cases of gastric cancer (p < 0.0001). All cholangiocarcinomas
      manifested themselves as purely intraductal masses, but five of the eight
      intraductal metastatic lesions were contiguous with parenchymal masses (p =
      0.031). The appearance of the intraductal lesion was predominantly expansile in
      cases of metastasis (seven of eight cases) but not in cases of cholangiocarcinoma
      (one of six cases) (p = 0.026). Other findings were not statistically significant
      in differentiating the two disease entities. CONCLUSION: When an intraductal
      lesion is found in a patient with extrabiliary malignancy, the presence of a
      contiguous parenchymal mass, an expansile nature of the intraductal lesion, and a
      history of colorectal cancer may suggest the presence of intraductal metastasis
      rather than double primary intraductal cholangiocarcinoma.

PMID- 19770331
TI  - Pitfalls in abdominal diffusion-weighted imaging: how predictive is restricted
      water diffusion for malignancy.
AB  - OBJECTIVE: As diffusion-weighted imaging is increasingly implemented into routine
      protocols of abdominal MRI, abnormal findings in expected and unexpected
      locations become more common. The aim of our retrospective study was to
      investigate the specificity of restricted diffusion in differentiation of benign
      from malignant abdominal disease. MATERIALS AND METHODS: Two hundred thirty
      consecutively registered patients underwent abdominal MRI including diffusion
      weighted imaging (single-shot spin-echo echo-planar sequence) with b values of 0,
      150, 500, and 1,000 s/mm(2). Lesions were detected by two blinded readers using
      only the images with a b value of 1,000 s/mm(2), and representative apparent
      diffusion coefficients were measured. Lymph nodes were not documented. RESULTS:
      Fifty-two of the 230 patients had a total of 55 lesions with restricted diffusion
      (23.9%). The mean apparent diffusion coefficient was 809 mm(2)/s. Forty-three
      lesions (78.2%) were malignant. The 12 benign lesions were liver hemangioma,
      liver adenoma, autoimmune pancreatitis, pancreatic teratoma, two abscesses, three
      cases of inflammatory bowel wall thickening due to Crohn's disease, Bartholin
      cyst, hemorrhagic ovarian cyst, and renal Rosai-Dorfman disease. CONCLUSION:
      Restricted diffusion is generally considered to be associated with malignant
      tumors because of the high cellularity of these tumors. However, in
      interpretation of diffusion-weighted images, it should be kept in mind that a
      number of benign lesions, as many as 22% in our cohort, can exhibit restricted
      diffusion on images with high b values, thus mimicking malignant lesions.

PMID- 19770332
TI  - Spontaneous abdominal hemorrhage: causes, CT findings, and clinical implications.
AB  - OBJECTIVE: The purpose of this article is to present the most common causes of
      spontaneous abdominal hemorrhage and to review the CT findings that are important
      in establishing the correct diagnosis and in guiding appropriate therapy.
      CONCLUSION: Knowledge of the common CT manifestations of various causes of
      spontaneous abdominal hemorrhage allows their accurate diagnosis and has a direct
      impact on clinical decision making.

PMID- 19770333
TI  - Tumor response in patients with advanced non-small cell lung cancer: perfusion CT
      evaluation of chemotherapy and radiation therapy.
AB  - OBJECTIVE: The objectives of this study were to prospectively evaluate changes in
      tumor perfusion after chemoradiation therapy and to investigate the feasibility
      of perfusion CT for prediction of early tumor response and prognosis of non-small
      cell lung cancer. SUBJECTS AND METHODS: Perfusion CT was performed on an MDCT
      scanner with 50 mL of iodinated contrast material injected at 4 mL/s. The quality
      of each functional map was rated from 0 to 3 for 123 patients with confirmed lung
      cancer. A subset of images was independently reviewed by two radiologists to
      measure interobserver and intraobserver variability. Perfusion parameters and
      tumor response were assessed for 35 patients with non-small cell lung cancer who
      underwent chemoradiation therapy. Progression-free survival and overall survival
      were analyzed for 22 patients who underwent repeated perfusion CT after therapy.
      RESULTS: Image quality was graded 2 (moderate) or 3 (good) in 68.2% of cases.
      High interobserver and intraobserver correlations of perfusion parameters were
      found on qualified images. The patients who responded to chemoradiation therapy
      had significantly greater blood flow (p = 0.023) than patients who did not
      respond. The median progression-free survival period of the patients with an
      increased permeability-surface area product was 4.7 months, significantly lower
      than the median progression-free survival period of 19.0 months among patients
      with a decreased permeability-surface area product (p < 0.001). The median
      overall survival period was 10.6 months for the group with an increased
      permeability-surface area product, significantly lower than the 19.3 months for
      the group with a decreased permeability-surface area product (p = 0.004).
      CONCLUSION: Non-small cell lung cancer with higher perfusion is more sensitive to
      chemoradiation therapy than that with lower perfusion. After chemoradiation
      therapy, findings at perfusion CT are a significant predictor of early tumor
      response and overall survival among patients with non-small cell lung cancer.

PMID- 19770334
TI  - Myocardial ischemia in acute coronary syndrome: assessment using 64-MDCT.
AB  - OBJECTIVE: We investigated the performance of 64-MDCT myocardial imaging in
      assessing myocardial ischemia in acute coronary syndrome (ACS). MATERIALS AND
      METHODS: Cardiac CT was performed in 35 patients with ACS: 24 patients with acute
      myocardial infarction (AMI) and 11 patients with unstable angina pectoris (UAP).
      We reconstructed 2D myocardial images at diastolic and systolic phases using the
      same raw data as those used for coronary CT angiography. The CT number in the
      myocardium was used as an estimate of ischemia. The myocardium was shown using a
      color scale that depicts faint low-density areas more clearly than gray scale. We
      evaluated the variations in myocardial enhancement during the cardiac cycle in
      the territory of the culprit lesion. In addition, we classified patients on the
      basis of the transmurality of myocardial enhancement and examined whether this
      feature correlates with myocardial damage. RESULTS: Myocardial imaging at systole
      showed myocardial hypoenhancement in territories of the culprit lesion in 91% of
      patients with ACS, 96% of patients with AMI, and 75% of patients with UAP. The
      hypoenhancement areas at systole tended to be more extensive than those at
      diastole. The transmural extent of hypoenhancement at systole correlated with
      myocardial damage, which was shown by myocardial biomarkers. CONCLUSION: CT
      myocardial imaging can be used to assess myocardial ischemia in the appropriate
      region of ACS with high sensitivity.

PMID- 19770335
TI  - Anomalies of visceroatrial situs.
AB  - OBJECTIVE: Visceroatrial situs refers to the position and configuration of the
      cardiac atria, the tracheobronchial tree, and the thoracoabdominal viscera.
      Accurate determination of situs is essential because anomalies of situs are
      associated with an increased incidence of complex congenital heart disease.
      CONCLUSION: We propose a methodical diagnostic approach to determining the
      visceroatrial situs and cardiac configuration that predicts the probability and
      types of associated congenital heart disease.

PMID- 19770336
TI  - CT findings in hydrocarbon pneumonitis after diesel fuel siphonage.
AB  - OBJECTIVE: The purpose of this study was to assess CT findings in a series of
      patients with hydrocarbon pneumonitis after diesel fuel siphonage. CONCLUSION:
      The characteristic CT findings of hydrocarbon pneumonitis after diesel fuel
      siphonage are the presence of air-space consolidations with predominant right
      middle lobe involvement and areas of low attenuation within consolidation.
      Occasionally, bronchoalveolar lavage is needed to confirm the diagnosis of
      hydrocarbon pneumonitis by the presence of lipid-laden macrophages on the basis
      of a history of diesel fuel aspiration.

PMID- 19770337
TI  - Frequency and severity of adverse effects of iodinated and gadolinium contrast
      materials: retrospective review of 456,930 doses.
AB  - OBJECTIVE: The purpose of this study was to determine the frequency and
      characteristics of adverse effects of low-osmolar iodinated and gadolinium
      contrast agents in a single-center experience with a large number of cases.
      MATERIALS AND METHODS: A retrospective review of all intravascular doses of low
      osmolar iodinated and gadolinium contrast materials administered from 2002
      through 2006 was conducted. Adverse effects were identified through the use of
      radiologist and nurse event recording. Adverse effects were examined for type and
      severity of reaction, treatment required, and outcome. RESULTS: A total of
      456,930 contrast doses (298,491 low-osmolar iodinated, 158,439 gadolinium) were
      administered over the study period. A total of 522 cases of adverse effects
      (0.11% of total) were identified (458 low-osmolar iodinated, 64 gadolinium). The
      most common adverse effects were hives (274, 52.5%) and nausea (92, 17.6%). Of
      all adverse effects, 79 of low-osmolar iodinated and 15 of gadolinium contrast
      material necessitated treatment. Most treatments were performed in the radiology
      department alone. Only 16 cases of adverse effects necessitated transfer for
      further observation or treatment. Epinephrine was used to manage an adverse
      effect in nine instances. Thirty-two of the adverse effects of low-osmolar
      iodinated contrast material (6.9%) occurred in patients with a history of allergy
      who received premedication. Only two of these premedication reactions
      necessitated transfer to the emergency department. The one death in the study
      period occurred after administration of low-osmolar iodinated contrast material.
      The patient had no symptoms during the contrast administration or imaging but
      died suddenly within 30 minutes of receiving the dose. CONCLUSION: Both iodinated
      and gadolinium contrast agents are associated with a very low rate of adverse
      effects. Most adverse effects are mild and can be managed in the radiology
      department. Transfer for additional treatment or observation is rarely needed.

PMID- 19770338
TI  - Adrenal imaging with MDCT: Nonneoplastic disease.
AB  - OBJECTIVE: The adrenal gland can enlarge or alter morphology in the presence of a
      range of nonneoplastic entities, including hyperplasia, hemorrhage, infection, or
      cystic mass. This article presents a description and representative CT images for
      each of these disorders. CONCLUSION: Proper characterization is essential to
      ensure that life-threatening sequelae from Addisonian crisis are averted in
      infection and hemorrhage, or to identify "leave-alone" lesions such as pseudocyst
      and chronic calcification.

PMID- 19770339
TI  - Trends in work hours and vacation time among radiologists in the United States.
AB  - OBJECTIVE: The purpose of this study was to describe recent trends in weekly work
      hours and annual vacation days among full-time radiologists in the United States
      with separate data for academic radiologists, radiologists in multispecialty
      groups, and radiologists in private practice. MATERIALS AND METHODS: We tabulated
      non-individually identified responses from the American College of Radiology
      1995, 2003, and 2007 surveys of radiologists. These stratified random sample
      surveys had, respectively, 2,025, 1,924, and 487 responses and response rates of
      75%, 63%, and 20%. Responses were weighted to make them representative of all
      U.S. radiologists. Respondents were assured of confidentiality. RESULTS: Mean
      weekly hours worked increased from 1995 to 2003 and from 2003 to 2007. The total
      increase was approximately 5 hours, or 10%. Mean vacation days also increased in
      both subperiods, from 27 in 1995 to 39 in 2007, yielding an approximately 5%
      decrease in days worked per year. The overall result was a mean increase of
      approximately 5% in annual work hours. In 2007, the 25th percentile of weekly
      hours was 45, and the 75th percentile was 55. The 25th percentile of annual
      vacation days was 25, and the 75th percentile was 50. Full-time radiologists
      responding about their own weekly hours reported, at the mean, working 10% more
      hours than they believed was the average for other full-time radiologists in the
      practice. CONCLUSION: Weekly hours and annual vacation days both have increased.
      The percentiles give radiologists a basis for comparison with other radiologists.
      Radiologists apparently often overestimate their work hours relative to the hours
      of others in their practices. Misperceptions of this kind might give rise to
      friction in radiology practices.

PMID- 19770340
TI  - Radiation dose for body CT protocols: variability of scanners at one institution.
AB  - OBJECTIVE: The objective of our study was to determine, using an anthropomorphic
      phantom, whether patients are subject to variable radiation doses based on
      scanner assignment for common body CT studies. MATERIALS AND METHODS: Twenty
      metal oxide semiconductor field effect transistor dosimeters were placed in a
      medium-sized anthropomorphic phantom of a man. Pulmonary embolism and chest,
      abdomen, and pelvis protocols were used to scan the phantom three times with GE
      Healthcare scanners in four configurations and one 64-MDCT Siemens Healthcare
      scanner. Organ doses were averaged, and effective doses were calculated with
      weighting factors. RESULTS: The mean effective doses for the pulmonary embolism
      protocol ranged from 9.9 to 18.5 mSv and for the chest, abdomen, and pelvis
      protocol from 6.7 to 18.5 mSv. For the pulmonary embolism protocol, the mean
      effective dose from the Siemens Healthcare 64-MDCT scanner was significantly
      lower than that from the 16- and 64-MDCT GE Healthcare scanners (p < 0.001). The
      mean effective dose from the GE 4-MDCT scanner was significantly lower than that
      for the GE 16-MDCT scanner (p < 0.001) but not the GE 64-MDCT scanner (p = 0.02).
      For the chest, abdomen, and pelvis protocol, all mean effective doses from the GE
      scanners were significantly different from one another (p < 0.001), the lowest
      mean effective dose being found with use of a single-detector CT scanner and the
      highest with a 4-MDCT scanner. For the chest, abdomen, and pelvis protocols, the
      difference between the mean effective doses from the GE Healthcare and Siemens
      Healthcare 64-MDCT scanners was not statistically significant (p = 0.89).
      CONCLUSION: According to phantom data, patients are subject to different
      radiation exposures for similar body CT protocols depending on scanner
      assignment. In general, doses are lowest with use of 64-MDCT scanners.

PMID- 19770341
TI  - MRI-guided injection procedures of the temporomandibular joints in children and
      adults: technique, accuracy, and safety.
AB  - OBJECTIVE: The purpose of our study was to test the hypothesis that real-time MRI
      guided, selective injection procedures of the temporomandibular joints are
      feasible, accurate, and safe when performed on a clinical open-bore 1.5-T MR
      system. MATERIALS AND METHODS: A retrospective analysis of 67 injection
      procedures of the temporomandibular joints (55% [37/67] were therapeutic
      injections, 27% [18/67] were diagnostic injections, and 18% [12/67] were
      arthrocentesis procedures), performed in 31 patients (58% [18/31] female, 42%
      [13/31] male; mean age, 14 years; age range, 3-34 years), was made. Seven of 38
      (18%) subjects had two temporally separate procedures. Determinations of skin
      entry points, puncture, and injection were performed under real-time MRI. Data
      were assessed for rate of successful injections, quantitative and qualitative
      image quality, time requirements, and occurrence of complications. RESULTS: Drug
      delivery was successful in all procedures. The quality of real-time FLASH 2D MR
      images was sufficient in all cases. Real-time MRI proved to be helpful to achieve
      high rates of intraarticular injections. Contrast-to-noise ratios were
      sufficiently high for good delineation of relevant structures. Average length of
      time was 25 minutes (range, 16-53 minutes). No major complications occurred.
      CONCLUSION: We accept the hypothesis that real-time MRI-guided selective
      injection procedures of the temporomandibular joints are feasible, accurate, and
      safe when performed on a clinical open-bore 1.5-T MR system.

PMID- 19770342
TI  - Value of 3D CT in defining skeletal complications of orthopedic hardware in the
      postoperative patient.
AB  - OBJECTIVE: Conventional CT of the postoperative patient with metal hardware is
      frequently limited by beam-hardening artifacts. With the evolution of 3D CT, CT
      is an increasingly effective means of examining the postsurgical patient for the
      integrity of their hardware and the course of their healing. CONCLUSION:
      Potential postsurgical complications such as nonunion, osteolysis, infection, and
      heterotopic ossification are all well assessed by 3D CT.

PMID- 19770343
TI  - Comparison of test performance characteristics of MRI, MR angiography, and CT
      angiography in the diagnosis of carotid and vertebral artery dissection: a review
      of the medical literature.
AB  - OBJECTIVE: Initial assessment of patients with suspected dissection of the
      carotid or vertebral arteries typically is made by MRI, alone or in combination
      with MR angiography (MRA) or CT angiography (CTA). We reviewed the medical
      literature to determine, based on test performance characteristics such as
      sensitivity, specificity, positive predictive value, and negative predictive
      value, whether evidence could be found to support routine use of one imaging
      technique over the other for assessment of suspected dissection. CONCLUSION: Test
      characteristics for MR techniques such as MRI and MRA were relatively similar to
      those for CTA in diagnosis of carotid and vertebral artery dissection.

PMID- 19770344
TI  - Fine-needle aspiration biopsy of thyroid nodules: experience in a cohort of 944
      patients.
AB  - OBJECTIVE: The objective of our study was to determine the likelihood of
      malignancy in thyroid nodules and the risk of a nondiagnostic fine-needle
      aspiration biopsy (FNAB) on the basis of the demographic characteristics of the
      patients and sonographic features of the nodules. MATERIALS AND METHODS: Between
      January 2002 and November 2007, 2,338 ultrasound-guided thyroid, thyroid bed, and
      cervical lymph node FNABs were performed at a tertiary referral center. Entry
      criteria for our retrospective study were adult patients who underwent thyroid
      nodule FNAB and had previously undergone diagnostic sonography. From previous
      reports for 944 thyroid nodules (739 nodules in women and 205 nodules in men),
      four sonographic features were recorded: longest dimension, morphology, presence
      of microcalcifications, and presence of lymphadenopathy. The final diagnosis of
      each nodule was classified as benign, malignant, or nondiagnostic on the basis of
      surgical pathology when available and cytology otherwise and was analyzed for
      correlation with individual sonographic features and combinations of features.
      RESULTS: The prevalence of malignancy and of nondiagnostic FNAB in this study was
      11.0% and 11.8%, respectively. Statistically significant (p < 0.05) findings in
      malignant nodules were younger patient age (< or = 45 years; odds ratio [OR],
      1.54) and solid nodule morphology (OR, 2.38). The significant predictors of a
      nondiagnostic-quality FNAB were older patient age (> 75 years; OR, 1.95) and a
      nodule > or = 10 mm (OR, 1.45). Adding information about the other evaluated
      ultrasound features did not lead to a significant result. CONCLUSION: Malignant
      thyroid nodules tend to be solid (86.5%). Patients older than 75 years showed a
      clearly increased risk of nondiagnostic FNAB, but to predict a higher risk of
      malignancy or of nondiagnostic FNAB using ultrasound remains difficult.

PMID- 19770345
TI  - Imaging findings of head and neck inflammatory pseudotumor.
AB  - OBJECTIVE: The purpose of this article is to describe imaging features of head
      and neck inflammatory pseudotumor in the brain, orbit, sinonasal cavity, temporal
      bone or skull base, and other rare locations. CONCLUSION: Although the radiologic
      differentiation from malignancy is not clearly possible, we suggest that
      familiarity with the manifestations of inflammatory pseudotumor can help avoid
      unnecessary radical surgery before histopathologic proof of malignancy.

PMID- 19770346
TI  - Mammographic screening in younger women at high risk.

PMID- 19770347
TI  - Rejection elicits emotional reactions but neither causes immediate distress nor
      lowers self-esteem: a meta-analytic review of 192 studies on social exclusion.
AB  - Competing predictions about the effect of social exclusion were tested by meta
      analyzing findings from studies of interpersonal rejection, ostracism, and
      similar procedures. Rejection appears to cause a significant shift toward a more
      negative emotional state. Typically, however, the result was an emotionally
      neutral state marked by low levels of both positive and negative affect.
      Acceptance caused a slight increase in positive mood and a moderate increase in
      self-esteem. Self-esteem among rejected persons was no different from neutral
      controls. These findings are discussed in terms of belongingness motivation,
      sociometer theory, affective numbing, and self-esteem defenses.

PMID- 19770348
TI  - Subcutaneous and intraperitoneal lipogranulomas following subcutaneous injection
      of olive oil in Sprague-Dawley rats.
AB  - Olive oil is commonly employed as a solubilizing agent for lipophilic materials
      in preclinical studies in rodents. Here we report that following subcutaneous
      (SC) injection of olive oil to Sprague-Dawley (SD) rats, local SC lipogranulomas
      formed, which were associated with an unusual location of the same changes in the
      peritoneum. Macroscopically, multifocal white spots were found over the liver and
      mesentery. Histologically, lipid granulomas were seen in the SC injection site,
      as well as on the capsular or serosal surface of the abdominal organs. No
      abnormal clinical signs were noted except for swelling at the injection site. The
      olive oil may have reached the peritoneal cavity from the SC tissue passively via
      the lymphatic vessels or actively after engulfment by antigen-presenting cells
      via the lymphatic or blood vessels. These findings are of particular importance
      for drug safety assessments, as the occurrence of lipogranulomas in locations
      distant from the site of administration may lead to misinterpretation of
      histological results. We suggest that these aberrations may be induced by the
      administration of olive oil as a vehicle.

PMID- 19770349
TI  - The pivotal role of electron microscopic evaluation in investigation of the
      cardiotoxicity of bis(2-chloroethoxy)methane in rats and mice.
AB  - Electron microscopy and light microscopy have been used to evaluate the
      cardiotoxicity of bis(2-chloroethoxy)methane (CEM) in F344/N rats and B6C3F1
      mice. Rats received vehicle control or CEM at 50 mg/kg/day, and mice, vehicle
      control or CEM at doses up to 100 mg/kg/day, by oral gavage for up to sixteen
      days. Cardiotoxicity in rats at 50 mg/kg consisted of myocardial degeneration,
      including myocardial inflammation, myofiber vacuolation, and/or myofiber
      necrosis. There was no light microscopic evidence for cardiotoxicity in mice even
      at doses twice that of rats, but cardiotoxic damage was seen after electron
      microscopic evaluations including mitochondrial disintegration and vacuolation.
      Mice with mitochondrial damage may be more susceptible to subsequent cardiotoxic
      events and have a reduced capacity to respond when energy demands increase. Oral
      treatment of rats with CEM caused cardiotoxic lesions similar to those reported
      after dermal administration (Dunnick, Johnson, et al. 2004). The F344/N rat is
      more sensitive than the B6C3F1 mouse to the cardiotoxic effects of CEM.

PMID- 19770352
TI  - The July 2005 London bombings: environmental monitoring, health risk assessment
      and lessons identified for major incident response.

PMID- 19770350
TI  - Activation of retinoic acid receptors by dihydroretinoids.
AB  - Vitamin A-derived metabolites act as ligands for nuclear receptors controlling
      the expression of a number of genes. Stereospecific saturation of the C(13)-C(14)
      double bond of all-trans-retinol by the enzyme, retinol saturase (RetSat), leads
      to the production of (R)-all-trans-13,14-dihydroretinol. In liver and adipose
      tissue, expression of RetSat is controlled by peroxisome proliferator-activated
      receptors (PPAR) alpha and gamma, respectively. Expression of RetSat in adipose
      tissue is also required for PPARgamma activation and adipocyte differentiation,
      but the involved mechanism is poorly understood. In this study, we examined the
      potential of (R)-all-trans-13,14-dihydroretinol and its metabolites to control
      gene transcription via nuclear receptors. Using a cell-based transactivation
      assay to screen 25 human nuclear receptors for activation, we found that
      dihydroretinoids have a narrow transcriptional profile limited primarily to
      activation of retinoic acid receptors (RARs). Although (R)-all-trans-13,14
      dihydroretinoic acid exhibited comparable potency to retinoic acid in promoting
      the interaction of RARs with a coactivator peptide in vitro, its potency in
      activating RAR-controlled genes in cell-based assays was much lower than that of
      retinoic acid. As an explanation for the weak RAR agonist activity of
      dihydroretinoids in cell-based assays, we propose that both delivery of ligand to
      the nucleus and RAR activation favor retinoic acid over dihydroretinoids.
      Discrimination between the cognate ligand, retinoic acid, and close analogs such
      as dihydroretinoids, occurs at multiple levels and may represent a mechanism to
      modulate retinoid-dependent physiological processes.

PMID- 19770351
TI  - Phosphatidylinositol (4,5)-bisphosphate regulation of N-methyl-D-aspartate
      receptor channels in cortical neurons.
AB  - The membrane phospholipid phosphatidylinositol (4,5)-bisphosphate (PIP(2)) has
      been implicated in the regulation of several ion channels and transporters. In
      this study, we examined the impact of PIP(2) on N-methyl-D-aspartate receptors
      (NMDARs) in cortical neurons. Blocking PIP(2) synthesis by inhibiting
      phosphoinositide-4 kinase, or stimulating PIP(2) hydrolysis via activation of
      phospholipase C (PLC), or blocking PIP(2) function with an antibody caused a
      significant reduction of NMDAR-mediated currents. On the other hand, inhibition
      of PLC or application of PIP(2) caused an enhancement of NMDAR currents. These
      electrophysiological effects were accompanied by changes in NMDAR surface
      clusters induced by agents that manipulate PIP(2) levels. The PIP(2) regulation
      of NMDAR currents was abolished by the dynamin inhibitory peptide, which blocks
      receptor internalization. Agents perturbing actin stability prevented PIP(2)
      regulation of NMDAR currents, suggesting the actin-dependence of this effect of
      PIP(2). Cofilin, a major actin depolymerizing factor, which has a common binding
      sequence for actin and PIP(2), was required for PIP(2) regulation of NMDAR
      currents. It is noteworthy that the PIP(2) regulation of NMDAR channels was
      impaired in a transgenic mouse model of Alzheimer's disease, probably because of
      the amyloid-beta disruption of PIP(2) metabolism. Taken together, our data
      suggest that continuous synthesis of PIP(2) at the membrane might be important
      for the maintenance of NMDARs at the cell surface. When PIP(2) is lost, cofilin
      is released from the PIP(2) complex and is rendered free to depolymerize actin.
      With the actin cytoskeleton no longer intact, NMDARs are internalized via a
      dynamin/clathrin-dependent mechanism, leading to reduced NMDAR currents.

PMID- 19770353
TI  - Paternal occupation and retinoblastoma: a case-control study based on data for
      Great Britain 1962-1999.
AB  - OBJECTIVES: To examine the association between paternal occupational exposures
      and retinoblastoma using birth registration data for cases from the National
      Registry of Childhood Tumours (NRCT) and controls from the general population of
      Great Britain. METHODS: A case-control study of paternal occupational data for
      1318 cases of retinoblastoma, born and diagnosed in Great Britain between 1962
      and 1999, and 1318 controls matched on sex, date of birth and birth registration
      sub-district. Paternal occupations at birth were grouped according to inferred
      exposure using an occupational exposure classification scheme. A conditional
      (matched) case-control analysis was used to estimate odds ratios (OR) and 95%
      confidence intervals (95% CI) for each paternal occupational exposure group.
      RESULTS: For non-heritable retinoblastoma, a statistically significant increased
      risk was found with father's definite occupational exposure to oil mists in metal
      working (OR = 1.85 (95% CI 1.05 to 3.36)). Together with a (non-significant) risk
      (OR = 1.64 (0.73 to 3.83)) amongst the heritable cases, this occupational
      exposure was also associated with a significant increased risk when all
      retinoblastoma cases were considered together (OR = 1.77 (1.12 to 2.85)). No
      statistically significant associations were observed for other exposure groups.
      CONCLUSIONS: Our finding for exposure to oil mists in metal working (a subset of
      metal workers) is not directly comparable to those for metal working previously
      reported in the literature. Overall, our findings do not support the hypothesis
      that paternal occupational exposure is an important aetiological factor for
      retinoblastoma, however, the study has low power and other methodological
      limitations.

PMID- 19770354
TI  - Effect of living close to a main road on asthma, allergy, lung function and
      chronic obstructive pulmonary disease.
AB  - BACKGROUND: A number of epidemiological studies suggest that the risk of asthma
      is increased among those living in close proximity to major roads. However, the
      evidence is inconsistent, and effects on asthma and related respiratory and
      allergic conditions using objective measures such as lung function and allergic
      sensitisation have not been widely investigated. METHODS: In 1995, 1996 and 2001
      data on respiratory and allergic disease, along with demographic and lifestyle
      factors, were collected in 59 285 children (aged 2-16 years) and adults as part
      of the Health Survey for England, a nationally representative annual survey.
      Using Geographical Information System software, we mapped the location of each
      participant's home and computed distance to the nearest major road. We estimated
      the effect of distance on self-reported wheezing in the past year, asthma, eczema
      and hay fever in 50 994 participants, and on 1-second forced expiratory volume
      (FEV(1)), immunoglobulin E and spirometry-defined chronic obstructive pulmonary
      disease (COPD) in subgroups of those aged 7+, 11+ and 16+ years, respectively.
      RESULTS: Living within 150 m from a major road was not significantly associated
      with an increased risk of any of the outcome variables in any age group (adjusted
      odds ratios ranged from 0.85 to 1.05). Furthermore there was little evidence that
      risk increased with increasing proximity across the 0-150 m range where contrasts
      in traffic-related pollutant concentrations are greatest. CONCLUSION: Our
      analysis of a large and nationally representative population sample did not
      provide evidence of an adverse effect of living in close proximity to main roads
      on the risk of asthma, COPD or allergic disease in England.

PMID- 19770355
TI  - Occupational physical activities, working hours and outcome of pregnancy:
      findings from the Southampton Women's Survey.
AB  - OBJECTIVES: To investigate risks of physical activity at work by pregnancy
      trimester, including the effects on head and abdominal circumference. METHOD: At
      34 weeks of gestation we interviewed 1327 mothers from the prospective
      Southampton Women's Survey (SWS); we asked about their activities (working hours,
      standing/walking, kneeling/squatting, trunk bending, lifting and night shifts) in
      jobs held at each of 11, 19 and 34 weeks of gestation, and subsequently
      ascertained four birth outcomes (preterm delivery, small for gestational age
      (SGA) and reduced head or abdominal circumference) blinded to employment history.
      RESULTS: Risk of preterm delivery was elevated nearly threefold in women whose
      work at 34 weeks entailed trunk bending for >1 h/day. Small head circumference
      was more common in babies born to women who worked for >40 h/week. However, no
      statistically significant associations were found with SGA or small abdominal
      circumference, and preterm delivery showed little association with long working
      hours, lifting, standing or shift work. CONCLUSIONS: There is a need for more
      research on trunk bending late in pregnancy, and on the relationship of work to
      reduced head circumference. Our findings on several other occupational exposures
      common among pregnant workers are reassuring.

PMID- 19770357
TI  - Comments on determinants of implementation of primary preventive interventions on
      patient handling in healthcare.

PMID- 19770359
TI  - Necdin restricts proliferation of hematopoietic stem cells during hematopoietic
      regeneration.
AB  - Hematopoietic stem cell (HSC) proliferation is tightly regulated by a poorly
      understood complex of positive and negative cell-cycle regulatory mechanisms.
      Necdin (Ndn) is an evolutionally conserved multifunctional protein that has been
      implicated in cell-cycle regulation of neuronal cells. Here, we provide evidence
      that necdin plays an important role in restricting excessive HSC proliferation
      during hematopoietic regeneration. We identify Ndn as being preferentially
      expressed in the HSC population on the basis of gene expression profiling and
      demonstrate that mice deficient in Ndn show accelerated recovery of the
      hematopoietic system after myelosuppressive injury, whereas no overt abnormality
      is seen in steady-state hematopoiesis. In parallel, after myelosuppression, Ndn
      deficient mice exhibit an enhanced number of proliferating HSCs. Based on these
      findings, we propose that necdin functions in a negative feedback loop that
      prevents excessive proliferation of HSCs during hematopoietic regeneration. These
      data suggest that the inhibition of necdin after clinical myelosuppressive
      treatment (eg, chemotherapy, HSC transplantation) may provide therapeutic
      benefits by accelerating hematologic recovery.

PMID- 19770358
TI  - High TCL1 levels are a marker of B-cell receptor pathway responsiveness and
      adverse outcome in chronic lymphocytic leukemia.
AB  - Although activation of the B-cell receptor (BCR) signaling pathway is implicated
      in the pathogenesis of chronic lymphocytic leukemia (CLL), its clinical impact
      and the molecular correlates of such response are not clearly defined. T-cell
      leukemia 1 (TCL1), the AKT modulator and proto-oncogene, is differentially
      expressed in CLL and linked to its pathogenesis based on CD5(+) B-cell expansions
      arising in TCL1-transgenic mice. We studied here the association of TCL1 levels
      and its intracellular dynamics with the in vitro responses to BCR stimulation in
      70 CLL cases. The growth kinetics after BCR engagement correlated strongly with
      the degree and timing of induced AKT phospho-activation. This signaling intensity
      was best predicted by TCL1 levels and the kinetics of TCL1-AKT corecruitment to
      BCR membrane activation complexes, which further included the kinases LYN, SYK,
      ZAP70, and PKC. High TCL1 levels were also strongly associated with aggressive
      disease features, such as advanced clinical stage, higher white blood cell
      counts, and shorter lymphocyte doubling time. Higher TCL1 levels independently
      predicted an inferior clinical outcome (ie, shorter progression-free survival, P
      < .001), regardless of therapy regimen, especially for ZAP70(+) tumors. We
      propose TCL1 as a marker of the BCR-responsive CLL subset identifying poor
      prognostic cases where targeting BCR-associated kinases may be therapeutically
      useful.

PMID- 19770360
TI  - Generation of EBV-specific cytotoxic T cells that are resistant to calcineurin
      inhibitors for the treatment of posttransplantation lymphoproliferative disease.
AB  - Epstein-Barr virus (EBV)-driven posttransplantation lymphoproliferative disease
      (PTLD) is a serious complication of immunosuppression after either stem cell
      transplantation (SCT) or solid organ transplantation (SOT). Adoptive transfer of
      EBV-specific cytotoxic T lymphocytes (EBV-CTLs) is an effective prophylaxis and
      treatment for PTLD after SCT, but not for PTLD after SOT when pharmacologic
      immunosuppression cannot be discontinued. We report the generation of calcineurin
      (CN) mutants that render EBV-CTL resistant to the immunosuppressants tacrolimus
      (FK506) and cyclosporin A (CsA): mutant CNa12 confers resistance to CsA but not
      FK506, and mutant CNa22 confers resistance to FK506 but not CsA, whereas mutant
      CNb30 renders CTLs resistant to both calcineurin inhibitors. Untransduced EBV
      CTLs do not proliferate in the presence of FK506/CsA. However, EBV-CTLs
      transduced with a retroviral vector coding for these mutants retain the ability
      to both proliferate and secrete normal levels of interferon-gamma in the presence
      therapeutic levels of FK506 (CNa12), CsA (CNa22), or both (CNb30). The
      cytotoxicity and phenotype of EBV-CTL lines were unaffected by expression of
      these mutant CNs. This approach should allow effective immunotherapy with EBV
      CTLs in the SOT setting without risking the graft by reduction in
      immunosuppression, and represents a generic approach to improving immunotherapy
      in the face of immunosuppression.

PMID- 19770361
TI  - Recombinant canine B-domain-deleted FVIII exhibits high specific activity and is
      safe in the canine hemophilia A model.
AB  - Production of recombinant B-domain-deleted canine factor VIII (cFVIII-BDD)
      unexpectedly revealed superior protein yields with 3-fold increased specific
      activity relative to human FVIII-BDD (hFVIII-BDD). We also determined that
      activated cFVIII-BDD is more stable than activated hFVIII-BDD. Furthermore,
      cFVIII-BDD is efficient at inducing hemostasis in human plasma containing FVIII
      inhibitors. Infusion of cFVIII-BDD in hemophilia A dogs resulted in correction of
      the disease phenotype with a pharmacokinetic profile similar to clinical
      experience with hFVIII-BDD. Notably, immune tolerance challenges with cFVIII-BDD
      in young and adult hemophilia A dogs did not induce the formation of neutralizing
      or nonneutralizing antibodies to cFVIII. These data establish the framework to
      quantitatively investigate the efficacy and safety in preclinical studies of
      novel therapies for hemophilia A.

PMID- 19770363
TI  - What does the medical profession mean by "standard of care?".

PMID- 19770362
TI  - Anti-CD3 antibodies modulate anti-factor VIII immune responses in hemophilia A
      mice after factor VIII plasmid-mediated gene therapy.
AB  - One major obstacle in gene therapy is the generation of immune responses directed
      against transgene product. Five consecutive anti-CD3 treatments concomitant with
      factor VIII (FVIII) plasmid injection prevented the formation of inhibitory
      antibodies against FVIII and achieved persistent, therapeutic levels of FVIII
      gene expression in treated hemophilia A mice. Repeated plasmid gene transfer is
      applicable in tolerized mice without eliciting immune responses. Anti-CD3
      treatment significantly depleted both CD4+ and CD8+ T cells, whereas increased
      transforming growth factor-beta levels in plasma and the frequency of both
      CD4+CD25+FoxP3+ and CD4+CD25-Foxp3+ regulatory T cells in the initial few weeks
      after treatment. Although prior depletion of CD4+CD25+ cells did not abrogate
      tolerance induction, adoptive transfer of CD4+ cells from tolerized mice at 6
      weeks after treatment protected recipient mice from anti-FVIII immune responses.
      Anti-CD3-treated mice mounted immune responses against both T-dependent and T
      independent neo-antigens, indicating that anti-CD3 did not hamper the immune
      systems in the long term. Concomitant FVIII plasmid + anti-CD3 treatment induced
      long-term tolerance specific to FVIII via a mechanism involving the increase in
      transforming growth factor-beta levels and the generation of adaptive FVIII
      specific CD4+Foxp3+ regulatory T cells at the periphery. Furthermore, anti-CD3
      can reduce the titers of preexisting anti-FVIII inhibitory antibodies in
      hemophilia A mice.

PMID- 19770364
TI  - Exploring the impact of the hormonal milieu on cognitive functioning.

PMID- 19770366
TI  - Thalidomide maintenance in multiple myeloma: certainties and controversies.

PMID- 19770367
TI  - Granuloma annulare heralding angioimmunoblastic T-cell lymphoma in a patient with
      a history of epstein-barr virus-associated B-cell lymphoma.

PMID- 19770369
TI  - Is preoperative chemoradiotherapy still the treatment of choice for rectal
      cancer?

PMID- 19770368
TI  - Underuse of breast cancer adjuvant treatment: patient knowledge, beliefs, and
      medical mistrust.
AB  - PURPOSE: Little is known about why women with breast cancer who have surgery do
      not receive proven effective postsurgical adjuvant treatments. METHODS: We
      surveyed 258 women who recently underwent surgical treatment at six New York City
      hospitals for early-stage breast cancer about their care, knowledge, and beliefs
      about breast cancer and its treatment. As per national guidelines, all women
      should have received adjuvant treatment. Adjuvant treatment data were obtained
      from inpatient and outpatient charts. Factor analysis was used to create scales
      scored to 100 of treatment beliefs and knowledge, medical mistrust, and physician
      communication about treatment. Bivariate and multivariate analyses assessed
      differences between treated and untreated women. RESULTS: Compared with treated
      women, untreated women were less likely to know that adjuvant therapies increase
      survival (on a 100-point scale; 66 v 75; P < .0001), had greater mistrust (64 v
      53; P = .001), and had less self-efficacy (92 v 97; P < .05); physician
      communication about treatment did not affect patient knowledge of treatment
      benefits (r = 0.8; P = .21). Multivariate analysis found that untreated women
      were more likely to be 70 years or older (adjusted relative risk [aRR], 1.11; 95%
      CI, 1.00 to 1.13), to have comorbidities (aRR, 1.10; 95% CI, 1.04 to 1.12), and
      to express mistrust in the medical delivery system (aRR, 1.003; 95% CI, 1.00 to
      1.007), even though they were more likely to believe adjuvant treatments were
      beneficial (aRR, 0.99; 95% CI, 0.98 to 0.99; model c, 0.84; P < or = .0001).
      CONCLUSION: Patient knowledge and beliefs about treatment and medical mistrust
      are mutable factors associated with underuse of effective adjuvant therapies.
      Physicians may improve cancer care by ensuring that discussions about adjuvant
      therapy include a clear presentation of the benefits, not just the risks of
      treatment, and by addressing patient trust in and concerns about the medical
      system.

PMID- 19770370
TI  - Synchronous advanced pure seminoma and diffuse large B-cell lymphoma: a case of
      multiple oncologic dilemmas.

PMID- 19770371
TI  - Primary testicular diffuse large B-cell lymphoma: a population-based study on the
      incidence, natural history, and survival comparison with primary nodal
      counterpart before and after the introduction of rituximab.
AB  - PURPOSE: We performed a population-based study of primary testicular diffuse
      large B-cell lymphoma (DLBCL) in the United States to determine its incidence and
      survival trends, prognostic factors, and clinical outcome compared with males
      with nodal DLBCL. PATIENTS AND METHODS: The Surveillance, Epidemiology, and End
      Results database was reviewed to identify patients diagnosed between 1980 and
      2005. To study the potential impact of the introduction of rituximab on survival,
      we used the year 2000 as cutoff point. RESULTS: We identified 769 patients with
      testicular DLBCL. The median age at diagnosis was 68.0 years. The incidence of
      DLBCL increased over time, with the highest rate among whites (twice that of
      blacks). The median overall survival (OS) for the whole group was 4.6 years,
      whereas the disease-specific survival (DSS) rates at 3, 5, and 15 years were
      71.5%, 62.4%, and 43.0%, respectively. Independent predictors of worse DSS were
      older age, diagnosis before 1986, advanced stage, left testicular involvement,
      and not having surgery and radiation. The use of radiation did not change
      significantly over time. When testicular and nodal DLBCL patients were analyzed
      together, testicular primary was an independent predictor of better OS and DSS.
      Unlike nodal DLBCL, DSS did not improve in the patients with testicular DLBCL
      diagnosed after the year 2000. CONCLUSION: The incidence of testicular DLBCL is
      increasing. Compared with nodal DLBCL, testicular DLBCL patients have a better
      overall prognosis but are at higher risk of late disease-related deaths. The
      introduction of rituximab in clinical practice does not seem to improve their
      early outcome.

PMID- 19770372
TI  - Low initial human papilloma viral load implicates worse prognosis in patients
      with uterine cervical cancer treated with radiotherapy.
AB  - PURPOSE: To evaluate whether human papillomavirus (HPV) viral load measured in
      cervical smear and HPV type 18 are associated with radiotherapy outcomes in
      uterine cervical cancer. PATIENTS AND METHODS HPV DNA: was semiquantitatively
      measured in the cervical smears of 169 radiotherapy patients. HPV viral load was
      classified as low or high according to median HPV DNA titer and examined for its
      prognostic value. The multivariable Cox proportional hazards model was used to
      adjust for covariates. A relapse-predicting model was constructed to classify
      three risk groups for disease-free survival (DFS), which were used for internal
      validation. RESULTS: Patients with lower HPV viral load showed worse DFS in
      univariate analysis. HPV type 18, younger patient age, stage group, nodal status,
      histologic grade, and histologic type were other prognostic factors for poor DFS.
      Among these factors, all except stage group were associated with HPV viral load.
      Multivariate analysis showed the strong influence of HPV viral load for poor DFS.
      The prognostic model developed using our outcome data performed well in
      predicting the risk of relapse. CONCLUSION: Our data suggest that HPV viral load
      is a strong independent prognostic factor for DFS. HPV type 18 showed a
      significant relationship with poor radiotherapy outcome in univariate analysis,
      but not in multivariate analysis.

PMID- 19770373
TI  - Vincristine, actinomycin, and cyclophosphamide compared with vincristine,
      actinomycin, and cyclophosphamide alternating with vincristine, topotecan, and
      cyclophosphamide for intermediate-risk rhabdomyosarcoma: children's oncology
      group study D9803.
AB  - PURPOSE: The purpose of this study was to compare the outcome of patients with
      intermediate-risk rhabdomyosarcoma (RMS) treated with standard VAC (vincristine,
      dactinomycin, and cyclophosphamide) chemotherapy to that of patients treated with
      VAC alternating with vincristine, topotecan, and cyclophosphamide (VAC/VTC).
      PATIENTS AND METHODS: Patients were randomly assigned to 39 weeks of VAC versus
      VAC/VTC; local therapy began after week 12. Patients with parameningeal RMS with
      intracranial extension (PME) were treated with VAC and immediate x-ray therapy.
      The primary study end point was failure-free survival (FFS). The study was
      designed with 80% power (5% two-sided alpha level) to detect an increase in 5
      year FFS from 64% to 75% with VAC/VTC. RESULTS: A total of 617 eligible patients
      were entered onto the study: 264 were randomly assigned to VAC and 252 to
      VAC/VTC; 101 PME patients were nonrandomly treated with VAC. Treatment strata
      were embryonal RMS, stage 2/3, group III (33%); embryonal RMS, group IV, less
      than age 10 years (7%); alveolar RMS or undifferentiated sarcoma (UDS), stage 1
      or group I (17%); alveolar RMS/UDS (27%); and PME (16%). At a median follow-up of
      4.3 years, 4-year FFS was 73% with VAC and 68% with VAC/VTC (P = .3). There was
      no difference in effect of VAC versus VAC/VTC across risk groups. The frequency
      of second malignancies was similar between the two treatment groups. CONCLUSION:
      For intermediate-risk RMS, VAC/VTC does not significantly improve FFS compared
      with VAC.

PMID- 19770374
TI  - Long-term results of a randomized trial of surgery with or without preoperative
      chemotherapy in esophageal cancer.
AB  - PURPOSE: OEO2 is a randomized, controlled trial of preoperative chemotherapy in
      patients undergoing radical surgery for esophageal cancer. Random assignment was
      to surgery alone (S) or to two cycles of combination cisplatin and fluorouracil
      before surgery (CS). Initial results reported in 2002 demonstrated an advantage
      for both disease-free and overall survival in the CS group. The analysis has now
      been updated after a median follow-up of 6 years. PATIENTS AND METHODS: OEO2
      recruited 802 patients, 400 on CS and 402 on S. The nature of the first
      recurrence event and cause of death are detailed. Survival has been determined
      from Kaplan-Meier curves and treatment comparisons made with the log-rank test.
      Survival by extent of resection is presented. RESULTS: There were 655 deaths, 335
      for S and 320 for CS. The survival benefit has been maintained with a hazard
      ratio (HR) of 0.84 (95% CI, 0.72 to 0.98; P = .03) which in absolute terms is a 5
      year survival of 23.0% for CS compared with 17.1% for S. The treatment effect is
      consistent in both adenocarcinoma and squamous cell carcinoma. The first disease
      free survival event was macroscopic residual disease from incomplete resection
      (R2) or no resection in 26.4% of the S group versus 14.3% of the CS P < .001.
      Three-year survival by type of resection was R0 42.4%, R1 was 18.0%, and R2 was
      8.6%. CONCLUSION: Long-term follow-up confirms that preoperative chemotherapy
      improves survival in operable esophageal cancer and should be considered as a
      standard of care.

PMID- 19770375
TI  - Serum 25-hydroxyvitamin D3 levels are associated with breslow thickness at
      presentation and survival from melanoma.
AB  - PURPOSE: A cohort study was carried out to test the hypothesis that higher
      vitamin D levels reduce the risk of relapse from melanoma. METHODS: A pilot
      retrospective study of 271 patients with melanoma suggested that vitamin D may
      protect against recurrence of melanoma. We tested these findings in a survival
      analysis in a cohort of 872 patients recruited to the Leeds Melanoma Cohort
      (median follow-up, 4.7 years). RESULTS: In the retrospective study, self-reports
      of taking vitamin D supplements were nonsignificantly correlated with a reduced
      risk of melanoma relapse (odds ratio = 0.6; 95% CI, 0.4 to 1.1; P = .09).
      Nonrelapsers had higher mean 25-hydroxyvitamin D(3) levels than relapsers (49 v
      46 nmol/L; P = .3; not statistically significant). In the cohort (prospective)
      study, higher 25-hydroxyvitamin D(3) levels were associated with lower Breslow
      thickness at diagnosis (P = .002) and were independently protective of relapse
      and death: the hazard ratio for relapse-free survival (RFS) was 0.79 (95% CI,
      0.64 to 0.96; P = .01) for a 20 nmol/L increase in serum level. There was
      evidence of interaction between the vitamin D receptor (VDR) BsmI genotype and
      serum 25-hydroxyvitamin D(3) levels on RFS. CONCLUSION: Results from the
      retrospective study were consistent with a role for vitamin D in melanoma
      outcome. The cohort study tests this hypothesis, providing evidence that higher
      25-hydroxyvitamin D(3) levels, at diagnosis, are associated with both thinner
      tumors and better survival from melanoma, independent of Breslow thickness.
      Patients with melanoma, and those at high risk of melanoma, should seek to ensure
      vitamin D sufficiency. Additional studies are needed to establish optimal serum
      levels for patients with melanoma.

PMID- 19770376
TI  - Preoperative multimodality therapy improves disease-free survival in patients
      with carcinoma of the rectum: NSABP R-03.
AB  - PURPOSE: Although chemoradiotherapy plus resection is considered standard
      treatment for operable rectal carcinoma, the optimal time to administer this
      therapy is not clear. The NSABP R-03 (National Surgical Adjuvant Breast and Bowel
      Project R-03) trial compared neoadjuvant versus adjuvant chemoradiotherapy in the
      treatment of locally advanced rectal carcinoma. PATIENTS AND METHODS: Patients
      with clinical T3 or T4 or node-positive rectal cancer were randomly assigned to
      preoperative or postoperative chemoradiotherapy. Chemotherapy consisted of
      fluorouracil and leucovorin with 45 Gy in 25 fractions with a 5.40-Gy boost
      within the original margins of treatment. In the preoperative group, surgery was
      performed within 8 weeks after completion of radiotherapy. In the postoperative
      group, chemotherapy began after recovery from surgery but no later than 4 weeks
      after surgery. The primary end points were disease-free survival (DFS) and
      overall survival (OS). RESULTS: From August 1993 to June 1999, 267 patients were
      randomly assigned to NSABP R-03. The intended sample size was 900 patients.
      Excluding 11 ineligible and two eligible patients without follow-up data, the
      analysis used data on 123 patients randomly assigned to preoperative and 131 to
      postoperative chemoradiotherapy. Surviving patients were observed for a median of
      8.4 years. The 5-year DFS for preoperative patients was 64.7% v 53.4% for
      postoperative patients (P = .011). The 5-year OS for preoperative patients was
      74.5% v 65.6% for postoperative patients (P = .065). A complete pathologic
      response was achieved in 15% of preoperative patients. No preoperative patient
      with a complete pathologic response has had a recurrence. CONCLUSION:
      Preoperative chemoradiotherapy, compared with postoperative chemoradiotherapy,
      significantly improved DFS and showed a trend toward improved OS.

PMID- 19770377
TI  - New lesions detected by single nucleotide polymorphism array-based chromosomal
      analysis have important clinical impact in acute myeloid leukemia.
AB  - PURPOSE: Cytogenetics is the primary outcome predictor in acute myeloid leukemia
      (AML). Metaphase cytogenetics (MC) detects an abnormal karyotype in only half of
      patients with AML, however. Single nucleotide polymorphism arrays (SNP-A) can
      detect acquired somatic uniparental disomy (UPD) and other cryptic defects, even
      in samples deemed normal by MC. We hypothesized that SNP-A will improve detection
      of chromosomal defects in AML and that this would enhance the prognostic value of
      MC. PATIENTS AND METHODS: We performed 250K and 6.0 SNP-A analyses on 140
      patients with primary (p) and secondary (s) AML and correlated the results with
      clinical outcomes and Flt-3/nucleophosmin (NPM-1) status. RESULTS: SNP-A is more
      sensitive than MC in detecting unbalanced lesions (pAML, 65% v 39%, P = .002; and
      sAML, 78% v 51%, P = .003). Acquired somatic UPD, not detectable by MC, was
      common in our AML cohort (29% in pAML and 35% in sAML). Patients with SNP-A
      lesions including acquired somatic UPD exhibited worse overall survival (OS) and
      event-free survival (EFS) in pAML with normal MC and in pAML/sAML with abnormal
      MC. SNP-A improved the predictive value of Flt-3 internal tandem duplication/NPM
      1 status, with inferior survival seen in patients with additional SNP-A defects.
      Multivariate analyses confirmed the independent predictive value of SNP-A defects
      for OS (hazard ratio [HR] = 2.52; 95% CI, 1.29 to 5.22; P = .006) and EFS (HR =
      1.72; 95% CI, 1.12 to 3.48; P = .04). CONCLUSION: SNP-A analysis allows enhanced
      detection of chromosomal abnormalities and provides important prognostic impact
      in AML.

PMID- 19770378
TI  - Randomized double-blind placebo-controlled trial of thalidomide in combination
      with gemcitabine and Carboplatin in advanced non-small-cell lung cancer.
AB  - PURPOSE: Cancers rely on angiogenesis for their growth and dissemination. We
      hypothesized that thalidomide, an oral antiangiogenic agent, when combined with
      chemotherapy, and as maintenance treatment, would improve survival in patients
      with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Seven
      hundred twenty-two patients were randomly assigned to receive placebo or
      thalidomide capsules 100 to 200 mg daily for up to 2 years. All patients received
      gemcitabine and carboplatin every 3 weeks for up to four cycles. End points were
      overall survival (OS), progression-free survival (PFS), response rate, grade 3/4
      toxicity, and quality of life (QoL). RESULTS: The median OS rates were 8.9 months
      (placebo) and 8.5 months (thalidomide). The hazard ratio (HR) was 1.13 (95% CI,
      0.97 to 1.32; P = .12). The 2-year survival rate was 16% and 12% in the placebo
      and thalidomide arms, respectively. The PFS results were consistent with those
      for OS. The risk of having a thrombotic event was increased by 74% in the
      thalidomide group: HR of 1.74 (95% CI, 1.20 to 2.52; P = .003). There were no
      differences in hematologic toxicities, but a slight excess of rash and neuropathy
      in the thalidomide group. QoL scores were similar but thalidomide was associated
      with less insomnia, and more constipation and peripheral neuropathy. In a
      retrospective analysis, patients with nonsquamous histology in the thalidomide
      group had a poorer survival: 2-year risk difference of 10% (95% CI, 4% to 16%; P
      < .001). CONCLUSION: In this large trial of patients with NSCLC, thalidomide in
      combination with chemotherapy did not improve survival overall, but increased the
      risk of thrombotic events. Unexpectedly, survival was significantly worse in
      patients with nonsquamous histology.

PMID- 19770379
TI  - Phase II study of yttrium-90-ibritumomab tiuxetan in patients with relapsed or
      refractory mantle cell lymphoma.
AB  - PURPOSE: This phase II trial evaluated the safety and efficacy of yttrium-90
      ((90)Y)-ibritumomab tiuxetan in patients with relapsed or refractory mantle cell
      lymphoma (MCL). PATIENTS AND METHODS: Patients with relapsed or refractory MCL
      were eligible for the study if they had adequate major organ function and
      performance status. Those with CNS disease, pleural effusion, circulating
      lymphoma cells > or = 5,000/microL, or history of stem-cell transplant were
      ineligible. Patients with a platelet count > or = 150,000/microL received a dose
      of 0.4 mCi/kg of (90)Y-ibritumomab tiuxetan, whereas those with a platelet count
      less than 150,000/microL received a dose of 0.3 mCi/kg. RESULTS: Thirty-four
      patients with a median age of 68 years (range, 52 to 79 years) received the
      therapeutic dose. The patients had received a median of three prior treatment
      regimens (range, one to six treatment regimens), including those that contained
      rituximab (n = 32) and bortezomib (n = 7). Of the 32 patients with measurable
      disease, 10 (31%) achieved complete or partial remission. After a median follow
      up of 22 months (range, 2 to 72+ months), an intent-to-treat analysis revealed a
      median event-free survival (EFS) duration of 6 months and an overall survival
      duration of 21 months. The median EFS for those who achieved partial or complete
      remission was 28 months, while it was 3 months for those whose disease did not
      respond (P < .0001); it was 9 months for patients whose tumor measured less than
      5 cm in the largest diameter before treatment and 3 months for those whose tumor
      measured > or = 5 cm (P = .015). CONCLUSION: The single-agent activity of (90)Y
      ibritumomab tiuxetan and its favorable safety profile warrant its further
      development for the treatment of MCL.

PMID- 19770380
TI  - Phase I pharmacokinetic and pharmacodynamic study of the aurora kinase inhibitor
      danusertib in patients with advanced or metastatic solid tumors.
AB  - PURPOSE: Danusertib (PHA-739358) is a small-molecule pan-aurora kinase inhibitor.
      This phase I dose escalation study was conducted to evaluate safety and
      tolerability of danusertib with additional pharmacokinetic, biomarker, and
      efficacy assessments. PATIENTS AND METHODS: Patients with solid tumors refractory
      to standard therapies or with no standard therapy available were enrolled.
      Danusertib was administered intravenously on days 1, 8, and 15 every 28 days in 6
      hour or 3-hour infusion schedules (ie, 6-hour IVS or 3-hour IVS). Dose levels
      from 45 mg/m(2) in the 6-hour IVS, and from 250 mg/m(2) in the 3-hour IVS, were
      studied. RESULTS: Fifty patients were treated. For the 6-hour IVS, the most
      frequently reported adverse effects were neutropenia (55%), nausea (25%),
      anorexia (23%), fatigue (20%), and diarrhea (18%). In the 3-hour IVS, fatigue
      (70%), neutropenia (60%), diarrhea (50%), and nausea (30%) were seen.
      Nonhematologic toxicity was mild to moderate. Neutropenia was dose limiting. The
      maximum-tolerated dose was 330 mg/m(2) for the 6-hour IVS and was not identified
      for the 3-hour IVS. The systemic exposure to danusertib increased linearly with
      dose. The infusion rate did not appear to remarkably influence the
      pharmacokinetics of danusertib. Biomarker analysis showed inhibition of histone
      H3 phosphorylation, indicative of aurora B inhibition, at doses of 190 mg/m(2) or
      greater. Stable disease was observed in 23.7% of evaluable patients, and disease
      stabilization occurred in 6 or more months in five patients. CONCLUSION: Dose
      limiting toxicity of danusertib is neutropenia, which was short lasting and
      generally uncomplicated; danusertib administration had limited nonhematologic
      toxicity. The recommended dose of danusertib for phase II studies is 330 mg/m(2)
      infused over 6 hours on days 1, 8, and 15 every 28 days.

PMID- 19770381
TI  - IKZF1 (Ikaros) deletions in BCR-ABL1-positive acute lymphoblastic leukemia are
      associated with short disease-free survival and high rate of cumulative incidence
      of relapse: a GIMEMA AL WP report.
AB  - PURPOSE: The causes of the aggressive nature of BCR-ABL1-positive adult acute
      lymphoblastic leukemia (ALL) are unknown. To identify, at the submicroscopic
      level, oncogenic lesions that cooperate with BCR-ABL1 to induce ALL, we performed
      an investigation of genomic copy number alterations using single nucleotide
      polymorphism array, genomic polymerase chain reaction, and sequencing of
      candidate genes. PATIENTS AND METHODS: Eighty-three patients with de novo adult
      Philadelphia chromosome (Ph) -positive ALL were enrolled onto institutional (n =
      17) or Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto Working Party
      delle Leucemia Acute (n = 66) clinical trials. Treatments included tyrosine
      kinase inhibitor (TKI) alone, conventional chemotherapy, or a combination of TKI
      and chemotherapy. RESULTS: A 7p12 deletion of IKZF1 (Ikaros) was identified in 52
      (63%) of 83 patients. The pattern of deletion varied among different patients,
      but the two most common deletion types were loss of exons 4 to 7 in 31 (37%) of
      83 patients and loss of exons 2 to 7 in 17 (20%) of 83 patients. Disease-free
      survival (DFS) was shorter in patients with IKZF1 deletion versus patients with
      IKZF1 wild type (10 v 32 months, respectively; P = .02). Furthermore, a
      significantly shorter cumulative incidence of relapse was recorded in patients
      with IKZF1 deletion versus patients with IKZF1 wild type (10.1 v 56.1 months,
      respectively; P = .001). Multivariate analysis confirmed the negative prognostic
      impact of IKZF1 deletion on DFS (P = .04). CONCLUSION: We conclude that IKZF1
      deletions are likely to be a genomic alteration that significantly affects the
      prognosis of Ph-positive ALL in adults.

PMID- 19770382
TI  - Effects of tamoxifen and raloxifene on memory and other cognitive abilities:
      cognition in the study of tamoxifen and raloxifene.
AB  - PURPOSE: To compare the effects of two selective estrogen receptor modulators,
      tamoxifen and raloxifene, on global and domain-specific cognitive function.
      PATIENTS AND METHODS: The National Surgical Adjuvant Breast and Bowel Project's
      Study of Tamoxifen and Raloxifene (STAR) study was a randomized clinical trial of
      tamoxifen 20 mg/d or raloxifene 60 mg/d in healthy postmenopausal women at
      increased risk of breast cancer. The 1,498 women who were randomly assigned in
      STAR were age 65 years and older, were not diagnosed with dementia, and were
      enrolled onto the Cognition in the Study of Tamoxifen and Raloxifene (Co-STAR)
      trial, beginning 18 months after STAR enrollment started. A cognitive test
      battery modeled after the one used in the Women's Health Initiative Study of
      Cognitive Aging (WHISCA) was administered. Technicians were centrally trained to
      administer the battery and recertified every 6 months. Analyses were conducted on
      all participants and on 273 women who completed the first cognitive battery
      before they started taking their medications. RESULTS: Overall, there were no
      significant differences in adjusted mean cognitive scores between the two
      treatment groups across visits. There were significant time effects across the
      three visits for some of the cognitive measures. Similar results were obtained
      for the subset of women with true baseline measures. CONCLUSION: Tamoxifen and
      raloxifene are associated with similar patterns of cognitive function in
      postmenopausal women at increased risk of breast cancer. Future comparisons
      between these findings and patterns of cognitive function in hormone therapy and
      placebo groups in WHISCA should provide additional insights into the effects of
      tamoxifen and raloxifene on cognitive function in older women.

PMID- 19770383
TI  - Phase I and pharmacokinetic study of cetuximab and irinotecan in children with
      refractory solid tumors: a study of the pediatric oncology experimental
      therapeutic investigators' consortium.
AB  - PURPOSE: To determine the dose of cetuximab that can be safely combined with
      irinotecan for treatment of pediatric and adolescent patients with refractory
      solid tumors. PATIENTS AND METHODS: This open-label, phase I study enrolled
      patients ages 1 to 18 years with advanced refractory solid tumors, including
      tumors of the CNS. Patient cohorts by age group (children, ages 1 to 12 years;
      adolescents, ages 13 to 18 years) received escalating weekly doses of cetuximab
      (75, 150, 250 mg/m(2)) in a 3 + 3 design, plus irinotecan (16 or 20 mg/m(2)/d)
      for 5 days for 2 consecutive weeks every 21 days. The primary end points were
      establishing the maximum-tolerated dose (MTD), recommended phase II dose (RPIID),
      and pharmacokinetics of the combination. Preliminary safety and efficacy data
      were also collected. RESULTS: Twenty-seven children and 19 adolescents received a
      median of 7.1 and 6.0 weeks of cetuximab therapy, respectively. Cetuximab 250
      mg/m(2) weekly plus irinotecan 16 mg/m(2)/d (pediatric) or 20 mg/m(2)/d
      (adolescent) have been established as the MTD/RPIID. Dose-limiting toxicities
      included diarrhea and neutropenia. Mild to moderate (grade 1 to 2) acneiform rash
      occurred in a majority of patients; no grade 3 to 4 rashes were observed.
      Cetuximab demonstrated dose-dependent clearance in both children and adolescents,
      similar to that in adults. There were two confirmed partial responses, both in
      patients with CNS tumors. Stable disease was achieved in 18 patients overall,
      including 10 patients with CNS tumors (38.5%). CONCLUSION: The
      cetuximab/irinotecan combination can be given safely to children and adolescents
      with cancer. Promising activity, particularly in CNS tumors, warrants phase II
      evaluation of this regimen.

PMID- 19770385
TI  - Human epidermal growth factor receptor 2-positive breast cancer and central
      nervous system metastases.
AB  - PURPOSE: To determine the incidence, outcomes, and current strategies for
      management of brain metastases in patients with human epidermal growth factor
      receptor 2 (HER2)-positive breast cancer. METHODS: A literature review was
      performed to obtain data on central nervous system metastases in patients with
      breast cancer. RESULTS: HER2 amplification/overexpression is a prognostic and
      predictive factor for the development of CNS metastases. Autopsy data show that
      the incidence rate for CNS metastases in patients with breast cancer is
      approximately 30%; this may be higher (ie, 30% to 50%) in patients with HER2
      positive disease. Treatment with trastuzumab is not associated with an increased
      incidence of CNS metastases. Data from three phase III adjuvant trials showed the
      incidence was similar between patients who received trastuzumab and those who did
      not. Furthermore, trastuzumab can significantly improve overall survival in HER2
      positive patients who already have CNS metastases compared with patients who do
      not receive trastuzumab or those who have HER2-negative brain metastases. This
      survival advantage is conferred via systemic control of the disease. The current
      standard of care for patients with CNS metastases is whole-brain radiotherapy
      (WBRT), with or without surgery, or stereotactic radiosurgery. In the future,
      novel therapies or combinations of therapies may additionally improve survival in
      these patients. CONCLUSION: The incidence of CNS metastases in trastuzumab
      treated patients is similar to that in all patients with HER2-positive disease.
      Trastuzumab can improve survival in patients with HER2-positive disease with CNS
      metastases.

PMID- 19770384
TI  - Identification and validation of a gene expression signature that predicts
      outcome in adult men with germ cell tumors.
AB  - PURPOSE: Germ cell tumor (GCT) is the most common malignancy in young adult men.
      Currently, patients are risk-stratified on the basis of clinical presentation and
      serum tumor markers. The introduction of molecular markers could improve outcome
      prediction. PATIENTS AND METHODS: Expression profiling was performed on 74
      nonseminomatous GCTs (NSGCTs) from cisplatin-treated patients (ie, training set)
      and on 34 similarly treated patients with NSGCTs (ie, validation set). A gene
      classifier was developed by using prediction analysis for microarrays (PAM) for
      the binary end point of 5-year overall survival (OS). A predictive score was
      developed for OS by using the univariate Cox model. RESULTS: In the training set,
      PAM identified 140 genes that predicted 5-year OS (cross-validated classification
      rate, 60%). The PAM model correctly classified 90% of patients in the validation
      set. Patients predicted to have good outcome had significantly longer survival
      than those with poor predicted outcome (P < .001). For the OS end point, a 10
      gene model had a predictive accuracy (ie, concordance index) of 0.66 in the
      training set and a concordance index of 0.83 in the validation set.
      Dichotomization of the samples on the basis of the median score resulted in
      significant differences in survival (P = .002). For both end points, the gene
      based predictor was an independent prognostic factor in a multivariate model that
      included clinical risk stratification (P < .01 for both). CONCLUSION: We have
      identified gene expression signatures that accurately predict outcome in patients
      with GCTs. These predictive genes should be useful for the prediction of patient
      outcome and could provide novel targets for therapeutic intervention.

PMID- 19770386
TI  - Multicenter randomized phase II study of weekly or twice-weekly bortezomib plus
      rituximab in patients with relapsed or refractory follicular or marginal-zone B
      cell lymphoma.
AB  - PURPOSE: To determine overall response rate (ORR), time to progression (TTP), and
      duration of response (DOR) with twice-weekly/weekly bortezomib plus rituximab,
      and evaluate safety/tolerability, in patients with relapsed or refractory CD20(+)
      follicular lymphoma (FL) or marginal-zone lymphoma. PATIENTS AND METHODS:
      Patients were randomly assigned (minimization method) to bortezomib 1.3 mg/m(2)
      twice weekly (days 1, 4, 8, and 11; 21-day cycle, five cycles; arm A) or
      bortezomib 1.6 mg/m(2) weekly (days 1, 8, 15, and 22; 35-day cycle, three cycles;
      arm B) plus rituximab 375 mg/m(2) weekly for 4 weeks (both arms).
      Response/progression was determined by International Workshop Response Criteria
      using oncologist/radiologist-adjudicated data from independent radiology review
      and investigator assessment. RESULTS: Eighty-one patients (arm A, n = 41; arm B,
      n = 40) were enrolled. Dose-intensity was higher in arm A; mean total bortezomib
      received was similar between arms (18.5 and 17.1 mg/m(2)). In arm A, ORR was 49%
      (14% complete response [CR]/CR unconfirmed [CRu]), median TTP was 7.0 months, and
      median DOR was not reached. In arm B, ORR was 43% (10% CR/CRu), and median
      TTP/DOR were 10.0/9.3 months. The weekly combination regimen seemed better
      tolerated. Grade 3 or worse adverse events seemed more common in arm A (54%)
      versus arm B (35%), including thrombocytopenia (10% v 0%) and peripheral
      neuropathy (10% v 5%), but diarrhea seemed less frequent (7% v 15%). No grade 4
      toxicities were reported in arm B. CONCLUSION: Both bortezomib plus rituximab
      regimens seem feasible in relapsed or refractory indolent lymphomas. The more
      convenient weekly combination regimen is being compared with single-agent
      rituximab in an ongoing phase III study in relapsed FL.

PMID- 19770387
TI  - ACCF/AHA/ACP 2009 competence and training statement: a curriculum on prevention
      of cardiovascular disease: a report of the American College of Cardiology
      Foundation/American Heart Association/American College of Physicians Task Force
      on Competence and Training (Writing Committee to Develop a Competence and
      Training Statement on Prevention of Cardiovascular Disease): developed in
      collaboration with the American Academy of Neurology; American Association of
      Cardiovascular and Pulmonary Rehabilitation; American College of Preventive
      Medicine; American College of Sports Medicine; American Diabetes Association;
      American Society of Hypertension; Association of Black Cardiologists; Centers for
      Disease Control and Prevention; National Heart, Lung, and Blood Institute;
      National Lipid Association; and Preventive Cardiovascular Nurses Association.

PMID- 19770388
TI  - AHA/ACCF [corrected] 2009 performance measures for primary prevention of
      cardiovascular disease in adults: a report of the American College of Cardiology
      Foundation/American Heart Association task force on performance measures (writing
      committee to develop performance measures for primary prevention of
      cardiovascular disease): developed in collaboration with the American Academy of
      Family Physicians; American Association of Cardiovascular and Pulmonary
      Rehabilitation; and Preventive Cardiovascular Nurses Association: endorsed by the
      American College of Preventive Medicine, American College of Sports Medicine, and
      Society for Women's Health Research.

PMID- 19770389
TI  - The importance of extinguishing secondhand smoke.

PMID- 19770390
TI  - Assessing the prognostic value of cardiovascular imaging: a statistical exercise
      or a guide to clinical value and application?

PMID- 19770391
TI  - Regulatory T cells modulate postischemic neovascularization.
AB  - BACKGROUND: CD4+ and CD8+ T lymphocytes are key regulators of postischemic
      neovascularization. T-cell activation is promoted by 2 major costimulatory
      signalings, the B7/CD28 and CD40-CD40 ligand pathways. Interestingly, CD28
      interactions with the structurally related ligands B7-1 and B7-2 are also
      required for the generation and homeostasis of CD4+CD25+ regulatory T cells (Treg
      cells), which play a critical role in the suppression of immune responses and the
      control of T-cell homeostasis. We hypothesized that Treg cell activation may
      modulate the immunoinflammatory response to ischemic injury, leading to
      alteration of postischemic vessel growth. METHODS AND RESULTS: Ischemia was
      induced by right femoral artery ligation in CD28-, B7-1/2-, or CD40-deficient
      mice (n=10 per group). CD40 deficiency led to a significant reduction in the
      postischemic inflammatory response and vessel growth. In contrast, at day 21
      after ischemia, angiographic score, foot perfusion, and capillary density were
      increased by 2.0-, 1.2-, and 1.8-fold, respectively, in CD28-deficient mice,
      which showed a profound reduction in the number of Treg cells compared with
      controls. Similarly, disruption of B7-1/2 signaling or anti-CD25 treatment and
      subsequent Treg deletion significantly enhanced postischemic neovascularization.
      These effects were associated with enhanced accumulation of CD3-positive T cells
      and Mac-3-positive macrophages in the ischemic leg. Conversely, treatment of
      CD28(-/-) mice with the nonmitogenic anti-CD3 monoclonal antibody enhanced the
      number of endogenous Treg cells and led to a significant reduction of the
      postischemic inflammatory response and neovascularization. Finally,
      coadministration of Treg cells and CD28(-/-) splenocytes in Rag1(-/-) mice with
      hindlimb ischemia abrogated the CD28(-/-) splenocyte-induced activation of the
      inflammatory response and neovascularization. CONCLUSIONS: Treg cell response
      modulates postischemic neovascularization.

PMID- 19770392
TI  - Declines in acute myocardial infarction after smoke-free laws and individual risk
      attributable to secondhand smoke.
AB  - BACKGROUND: The estimated effects of recent pubic and workplace smoking
      restriction laws suggest that they produce significant declines in community
      rates of heart attack. The consistency of these declines with existing estimates
      of the relative risk of heart attack in individuals attributable to passive
      smoking exposure is poorly understood. The objective is to determine the
      consistency of estimates of reductions in community rates of heart attacks
      resulting from smoking restriction laws with estimates of the relative risk of
      heart disease in individuals exposed to passive smoking. METHODS AND RESULTS:
      Meta-analyses of existing estimates of declines in community rates were compared
      with a mathematical model of the relationship between individual risk and
      community rates. The outcome measure is the ratio of community rates of acute
      myocardial infarction (after divided by before implementation of a smoking
      restriction law). There is a significant drop in the rate of acute myocardial
      infarction hospital admissions associated with the implementation of strong smoke
      free legislation. The primary reason for heterogeneity in results of different
      studies is the duration of follow-up after adoption of the law. The pooled random
      effects estimate of the rate of acute myocardial infarction hospitalization 12
      months after implementation of the law is 0.83 (95% confidence interval, 0.80 to
      0.87), and this benefit grows with time. This drop in admissions is consistent
      with a range of plausible individual risk and exposure scenarios. CONCLUSIONS:
      Passage of strong smoke-free legislation produces rapid and substantial benefits
      in terms of reduced acute myocardial infarctions, and these benefits grow with
      time.

PMID- 19770393
TI  - Myocardial salvage through coronary collateral growth by granulocyte colony
      stimulating factor in chronic coronary artery disease: a controlled randomized
      trial.
AB  - BACKGROUND: The efficacy of granulocyte colony-stimulating factor (G-CSF) for
      coronary collateral growth promotion and thus impending myocardial salvage has
      not been studied so far, to our best knowledge. METHODS AND RESULTS: In 52
      patients with chronic stable coronary artery disease, age 62+/-11 years, the
      effect on a marker of myocardial infarct size (ECG ST segment elevation) and on
      quantitative collateral function during a 1-minute coronary balloon occlusion was
      tested in a randomized, placebo-controlled, double-blind fashion. The study
      protocol before coronary intervention consisted of occlusive surface and
      intracoronary lead ECG recording as well as collateral flow index (CFI, no unit)
      measurement in a stenotic and a > or =1 normal coronary artery before and after a
      2-week period with subcutaneous G-CSF (10 microg/kg; n=26) or placebo (n=26). The
      CFI was determined by simultaneous measurement of mean aortic, distal coronary
      occlusive, and central venous pressure. The ECG ST segment elevation >0.1 mV
      disappeared significantly more often in response to G-CSF (11/53 vessels; 21%)
      than to placebo (0/55 vessels; P=0.0005), and simultaneously, CFI changed from
      0.121+/-0.087 at baseline to 0.166+/-0.086 at follow-up in the G-CSF group, and
      from 0.152+/-0.082 to 0.131+/-0.071 in the placebo group (P<0.0001 for
      interaction of treatment and time). The absolute change in CFI from baseline to
      follow-up amounted to +0.049+/-0.062 in the G-CSF group and to -0.010+/-0.060 in
      the placebo group (P<0.0001). CONCLUSIONS: Subcutaneous G-CSF is efficacious
      during a short-term protocol in improving signs of myocardial salvage by coronary
      collateral growth promotion.

PMID- 19770394
TI  - Survival and cardiac remodeling after myocardial infarction are critically
      dependent on the host innate immune interleukin-1 receptor-associated kinase-4
      signaling: a regulator of bone marrow-derived dendritic cells.
AB  - BACKGROUND: The innate immune system greatly contributes to the inflammatory
      process after myocardial infarction (MI). Interleukin-1 receptor-associated
      kinase-4 (IRAK-4), downstream of Toll/interleukin-1 receptor signaling, has an
      essential role in regulating the innate immune response. The present study was
      designed to determine the mechanism by which IRAK-4 is responsible for the
      cardiac inflammatory process, which consequently affects left ventricular
      remodeling after MI. METHODS AND RESULTS: Experimental MI was created in IRAK-4(
      /-) and wild-type mice by left coronary ligation. Mice with a targeted deletion
      of IRAK-4 had an improved survival rate at 4 weeks after MI. IRAK-4(-/-) mice
      also demonstrated attenuated cardiac dilation and decreased inflammation in the
      infarcted myocardium, which was associated with less proinflammatory and Th1
      cytokine expression mediated by suppression of nuclear factor-kappaB and c-Jun N
      terminal kinase activation. IRAK-4(-/-) mice had fewer infiltrations of CD45+
      leukocytes and CD11c+ dendritic cells, inhibition of apoptosis, and reduced
      fibrosis and nitric oxide production. Cardiac dendritic cells in IRAK-4(-/-) mice
      were relatively immature or functionally naive after MI in that they demonstrated
      less cytokine and costimulatory molecule gene expression. Furthermore, IRAK-4(-/
      ) dendritic cells have less mobilization capacity. Transfer of wild type-derived
      bone marrow dendritic cells into IRAK-4(-/-) mice for functional dendritic cell
      reconstitution negated the survival advantage and reduced the cardiac dilation
      observed with IRAK-4(-/-) mice at 28 days after MI. CONCLUSIONS: Deletion of IRAK
      4 has favorable effects on survival and left ventricular remodeling after MI
      through modification of the host inflammatory process by blunting the detrimental
      bone marrow dendritic cells mobilization after myocardial ischemia.

PMID- 19770395
TI  - Effects of telmisartan, ramipril, and their combination on left ventricular
      hypertrophy in individuals at high vascular risk in the Ongoing Telmisartan Alone
      and in Combination With Ramipril Global End Point Trial and the Telmisartan
      Randomized Assessment Study in ACE Intolerant Subjects With Cardiovascular
      Disease.
AB  - BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors and angiotensin
      receptor blockers reduce left ventricular hypertrophy (LVH). The effect of these
      drugs on LVH in high-risk patients without heart failure is unknown. METHODS AND
      RESULTS: In the Ongoing Telmisartan Alone and in Combination With Ramipril Global
      End Point Trial (ONTARGET), patients at high vascular risk and tolerant of ACE
      inhibitors were randomly assigned to ramipril, telmisartan, or their combination
      (n=23 165). In the Telmisartan Randomized Assessment Study in ACE Intolerant
      Subjects With Cardiovascular Disease (TRANSCEND), patients intolerant of ACE
      inhibitors were randomized to telmisartan or placebo (n=5343). Prevalence of LVH
      at entry in TRANSCEND was 12.7%. It was reduced by telmisartan (10.5% and 9.9%
      after 2 and 5 years) compared with placebo (12.7% and 12.8% after 2 and 5 years)
      (overall odds ratio, 0.79; 95% confidence interval [CI], 0.68 to 0.91; P=0.0017).
      New-onset LVH occurred less frequently with telmisartan compared with placebo
      (overall odds ratio, 0.63; 95% CI, 0.51 to 0.79; P=0.0001). LVH regression was
      similar in the 2 groups. In ONTARGET, prevalence of LVH at entry was 12.4%. At
      follow-up, it occurred slightly less frequently with telmisartan (odds ratio,
      0.92; 95% CI, 0.83 to 1.01; P=0.07) and the combination (odds ratio, 0.93; 95%
      CI, 0.84 to 1.02; P=0.12) than with ramipril, but differences between the groups
      were not significant. New-onset LVH was associated with a higher risk of primary
      outcome during follow-up (hazard ratio, 1.77; 95% CI, 1.50 to 2.07). CONCLUSIONS:
      In patients at high vascular risk, telmisartan is more effective than placebo in
      reducing LVH. New-onset LVH is reduced by 37%. The effect of combination of the 2
      drugs on LVH is similar to that of ramipril alone.

PMID- 19770396
TI  - Accelerated telomere shortening in leukocyte subpopulations of patients with
      coronary heart disease: role of cytomegalovirus seropositivity.
AB  - BACKGROUND: Shortening of mean telomere length (TL) in white blood cells is
      correlated with the development of coronary heart disease (CHD) and with
      increased mortality due to infectious disease. The goal of the present study was
      to investigate whether telomere shortening in CHD is restricted to specific
      peripheral blood lymphocyte and/or myeloid cell subpopulations. Results were
      correlated to TL in CD34+ hematopoietic peripheral blood stem cells and
      progenitor cells obtained from the same individual patients. METHODS AND RESULTS:
      TL was measured by multicolor flow cytometry-fluorescent in situ hybridization in
      12 leukocyte subpopulations after immunomagnetic bead sorting. We investigated TL
      in 14 young (mean age 25 years) and 13 older (mean age 65 years) healthy male
      volunteers and in 25 age-matched patients with CHD (mean age 65 years). We show
      that TL in granulocytes and monocytes mirrors TL of CD34+ peripheral blood stem
      cells and progenitor cells extremely well (r=0.95, P<0.0001) in patients and in
      healthy adults. TL was approximately 0.5 kilobases (kb) shorter in leukocytes
      from patients with CHD than in their age-matched control subjects. This
      difference was identical for CD34+ peripheral blood stem cells and progenitor
      cells, monocytes, granulocytes, B lymphocytes, and CD4+ T cells, including their
      memory and naive subpopulations. Surprisingly, only in cytotoxic CD8+ T
      lymphocytes, we found a substantially increased TL deficit of 1.0 kb in CHD
      patients as opposed to control subjects. Further analysis revealed that TL
      shortening was particularly pronounced in CD8+CD28(-) T cells obtained from
      cytomegalovirus-seropositive CHD patients, whereas such a difference was not
      observed in healthy cytomegalovirus-positive as opposed to cytomegalovirus
      negative control subjects. Finally, TL shortening of CD8+CD45(RA+) T cells was
      correlated with the decrease in left ventricular function in CHD patients
      (r=0.629, P=0.001). CONCLUSIONS: Telomere shortening in patients with CHD could
      potentially be attributed to either inherited TL shortening or acquired
      accelerated telomere shortening restricted to the hematopoietic system, which
      affects the baseline TL of all peripheral blood cell populations, including
      peripheral blood stem cells and progenitor cells. In addition, cytomegalovirus
      seropositive patients but not healthy control subjects exhibited further
      shortening of their cytotoxic T lymphocytes. Surprisingly, TL shortening of CD8+
      T lymphocytes in CHD patients demonstrated a very strong correlation with cardiac
      dysfunction, which suggests a mechanistic link between CHD and immunosenescence.

PMID- 19770397
TI  - Intra-cardiopulmonary resuscitation hypothermia with and without volume loading
      in an ischemic model of cardiac arrest.
AB  - BACKGROUND: We investigated the effects of intra-cardiopulmonary resuscitation
      (CPR) hypothermia with and without volume loading on return to spontaneous
      circulation and infarction size in an ischemic model of cardiac arrest. METHODS
      AND RESULTS: Using a distal left anterior descending artery occlusion model of
      cardiac arrest followed by resuscitation with a total of 120 minutes of occlusion
      and 90 minutes of reperfusion, we randomized 46 pigs into 5 groups and used
      myocardial staining to define area at risk and myocardial necrosis. Group A had
      no intervention. Immediately after return of spontaneous circulation, group B
      received surface cooling with cooling blankets and ice. Group C received intra
      CPR 680+/-23 mL of 28 degrees C 0.9% normal saline via a central venous catheter.
      Group D received intra-CPR 673+/-26 mL of 4 degrees C normal saline followed by
      surface cooling after return of spontaneous circulation. Group E received intra
      CPR and hypothermia after return of spontaneous circulation with an endovascular
      therapeutic hypothermia system placed in the right atrium and set at a target of
      32 degrees C. Intra-CPR volume loading with room temperature (group C) or iced
      saline (group D) significantly (P<0.05) decreased coronary perfusion pressure
      (group C, 12.8+/-4.78 mm Hg; group D, 14.6+/-9.9 mm Hg) compared with groups A,
      B, and E (20.6+/-8.2, 20.1+/-7.8, and 21.3+/-12.4 mm Hg). Return of spontaneous
      circulation was significantly improved in group E (9 of 9) compared with groups A
      plus B and C (10 of 18 and 1 of 8). The percent infarction to the area at risk
      was significantly reduced with intra-CPR hypothermia in groups D (24.3+/-4.2%)
      and E (4+/-3.4%) compared with groups A (72+/-5.1%) and B (67.3+/-4.2%).
      CONCLUSIONS: Intra-CPR hypothermia significantly reduces myocardial infarction
      size. Elimination of volume loading further improves outcomes.

PMID- 19770398
TI  - Neuronal nitric oxide synthase protects against myocardial infarction-induced
      ventricular arrhythmia and mortality in mice.
AB  - BACKGROUND: Neuronal nitric oxide synthase (nNOS) is expressed in cardiomyocytes
      and plays a role in regulating cardiac function and Ca2+ homeostasis. However,
      the role of nNOS in cardiac electrophysiology after myocardial infarction (MI) is
      unclear. We hypothesized that nNOS deficiency increases ventricular arrhythmia
      and mortality after MI. METHODS AND RESULTS: MI was induced in wild-type (WT) or
      nNOS(-/-) mice by ligation of the left coronary artery. Thirty-day mortality was
      significantly higher in nNOS(-/-) compared with WT mice. Additionally, nNOS(-/-)
      mice had impaired cardiac function 2 days after MI. Telemetric ECG monitoring
      showed that compared with WT, nNOS(-/-) mice had significantly more ventricular
      arrhythmias and were more likely to develop ventricular fibrillation after MI.
      Treatment with the L-type Ca2+ channel blocker verapamil reduced the incidence of
      arrhythmia and ventricular fibrillation in nNOS(-/-) mice after MI. To assess the
      role of nNOS in Ca2+ handling, patch-clamp and Ca2+ fluorescence techniques were
      used. Ca2+ transients and L-type Ca2+ currents were higher in nNOS(-/-) compared
      with WT cardiomyocytes. Additionally, nNOS(-/-) cardiomyocytes exhibited
      significantly higher systolic and diastolic Ca2+ over a range of pacing
      frequencies. Treatment with the NO donor S-nitroso N-acetyl-penicillamine
      decreased Ca2+ transients and L-type Ca2+ current in both nNOS(-/-) and WT
      cardiomyocytes. Furthermore, S-nitrosylation of Ca2+ handling proteins was
      significantly decreased in nNOS(-/-) myocardium after MI. CONCLUSIONS: Deficiency
      in nNOS increases ventricular arrhythmia and mortality after MI in mice. The
      antiarrhythmic effect of nNOS involves inhibition of L-type Ca2+ channel activity
      and regulation of Ca2+ handling proteins via S-nitrosylation.

PMID- 19770399
TI  - Complementary prognostic values of stress myocardial perfusion and late
      gadolinium enhancement imaging by cardiac magnetic resonance in patients with
      known or suspected coronary artery disease.
AB  - BACKGROUND: Recent studies have demonstrated the significant prognostic value of
      stress cardiac magnetic resonance (CMR) myocardial perfusion imaging. Apart from
      characterizing reversible perfusion defect (RevPD) from flow-limiting coronary
      stenosis, CMR late gadolinium enhancement (LGE) imaging is currently the most
      sensitive method for detecting subendocardial infarction (MI). We therefore
      tested the hypothesis that characterization of these 2 processes from coronary
      artery disease by CMR can provide complementary prognostic values. METHODS AND
      RESULTS: We performed CMR myocardial perfusion imaging followed by LGE imaging on
      254 patients referred with symptoms of myocardial ischemia. At a median follow-up
      of 17 months, 49 cardiac events occurred, including 12 cardiac deaths, 16 acute
      MIs, and 21 cardiac hospitalizations. RevPD and LGE both maintained a >3-fold
      association with cardiac death or acute MI (death/MI) when adjusted for each
      other and for the effects of patient age and gender (adjusted hazard ratio, 3.31;
      P=0.02; and hazard ratio, 3.43; P=0.01, respectively). In patients without a
      history of MI who had negative RevPD, LGE presence was associated with a >11-fold
      hazards increase in death/MI. Patients with neither RevPD nor LGE had a 98.1%
      negative annual event rate for death/MI. For association with major adverse
      cardiac events, RevPD was the strongest multivariable variable in the best
      overall model (hazard ratio, 10.92; P<0.0001). CONCLUSIONS: CMR imaging provides
      robust risk stratification for patients who present with symptoms of ischemia.
      Characterization of RevPD and LGE by CMR provides strong and complementary
      prognostic implication for cardiac death or acute MI.

PMID- 19770400
TI  - Sildenafil increases endothelial progenitor cell function and improves ischemia
      induced neovascularization in hypercholesterolemic apolipoprotein E-deficient
      mice.
AB  - Hypercholesterolemia is associated with impaired neovascularization in response
      to ischemia. Potential mechanisms include defective NO bioactivity and a
      reduction in the number/function of endothelial progenitor cells (EPCs). Here we
      tested the hypothesis that sildenafil, a phosphodiesterase 5 inhibitor that
      increases NO-driven cGMP levels, could stimulate EPC function and improve
      ischemia-induced neovascularization in hypercholesterolemic conditions.
      Apolipoprotein E-deficient (ApoE(-/-)) mice were treated (or not treated) with
      sildenafil (40 mg/kg per day in water), and hindlimb ischemia was surgically
      induced by femoral artery removal. Sildenafil treatment led to an improved blood
      flow recovery, an increased capillary density, and a reduction of oxidative
      stress levels in ischemic muscles at day 7 after surgery. Sildenafil therapy is
      associated with an increased activation of angiogenic transduction pathways,
      including Akt, p44/42 mitogen-activated protein kinase, and p38. In vitro,
      sildenafil increases cellular migration and tubule formation of mature
      endothelial cells (human umbilical vascular endothelial cells) in a cGMP
      dependent manner. In vivo, ApoE(-/-) mice treated with sildenafil exhibit a
      significant increase in the number of bone marrow-derived EPCs. Moreover, the
      angiogenic activities of EPCs (migration and adhesion) are significantly improved
      in ApoE(-/-) mice treated with sildenafil. In summary, this study demonstrates
      that sildenafil treatment is associated with improved ischemia-induced
      neovascularization in hypercholesterolemic ApoE(-/-) mice. The mechanisms involve
      beneficial effects on angiogenic transduction pathways together with an increase
      in the number and the functional activity of EPCs. Sildenafil could constitute a
      novel therapeutic strategy to reduce tissue ischemia in atherosclerotic diseases.

PMID- 19770401
TI  - Determination of travel distance for noninvasive measurement of pulse wave
      velocity: case closed?

PMID- 19770402
TI  - Leptin impairs cardiovagal baroreflex function at the level of the solitary tract
      nucleus.
AB  - Circulating leptin is elevated in some forms of obesity-related hypertension,
      associated with impaired baroreflex function. Leptin receptors are present on
      vagal afferent fibers and neurons within the solitary tract nucleus, providing an
      anatomic distribution consistent with baroreflex modulation. Although solitary
      tract nucleus microinjection of 144 fmol/60 nL of leptin had no significant
      effect on baroreflex sensitivity for control of the heart rate in
      urethane/chloralose-anesthetized Sprague-Dawley rats, 500 fmol of leptin impaired
      baroreflex sensitivity for bradycardia in response to increases in pressure
      (1.15+/-0.04 versus 0.52+/-0.12 ms/mm Hg; P<0.01). Transgenic ASrAOGEN rats with
      low brain angiotensinogen have an upregulation of the leptin receptor and p85
      alpha mRNA in the dorsal medulla relative to Sprague-Dawley rats. Consistent with
      these observations, the response to leptin was enhanced in ASrAOGEN rats, because
      both the 144-fmol (1.46+/-0.08 versus 0.75+/-0.10 ms/mm Hg; P<0.001) and 500-fmol
      (1.36+/-0.32 versus 0.44+/-0.06 ms/mm Hg; P<0.05) leptin microinjections impaired
      baroreflex sensitivity. At these doses, leptin microinjection had no effect on
      resting pressure, heart rate, or the tachycardic response to decreases in
      pressure in Sprague-Dawley or ASrAOGEN rats. Thus, exogenous leptin at sites
      within the solitary tract nucleus impairs the baroreflex sensitivity for
      bradycardia induced by increases in arterial pressure, consistent with a
      permissive role in mediating increases in arterial pressure. Baroreflex
      inhibition was enhanced in animals with evidence of increased leptin receptor and
      relevant signaling pathway mRNA.

PMID- 19770403
TI  - A new PIXel in the puzzle: how increased vascular pressure induces oxidative
      stress.

PMID- 19770404
TI  - Intrarenal dopamine attenuates deoxycorticosterone acetate/high salt-induced
      blood pressure elevation in part through activation of a medullary cyclooxygenase
      2 pathway.
AB  - Locally produced dopamine in the renal proximal tubule inhibits salt and fluid
      reabsorption, and a dysfunctional intrarenal dopaminergic system has been
      reported in essential hypertension and experimental hypertension models. Using
      catechol-O-methyl-transferase knockout (COMT(-/-)) mice, which have increased
      renal dopamine because of deletion of the major renal dopamine-metabolizing
      enzyme, we investigated the effect of intrarenal dopamine on the development of
      hypertension in the deoxycorticosterone acetate/high-salt (DOCA/HS) model.
      DOCA/HS led to significant increases in systolic blood pressure in wild-type mice
      (from 115+/-2 to 153+/-4 mm Hg), which was significantly attenuated in COMT(-/-)
      mice (from 114+/-2 to 135+/-3 mm Hg). In DOCA/HS COMT(-/-) mice, the D1-like
      receptor antagonist SCH-23390 increased systolic blood pressure (156+/-2 mm Hg).
      DOCA/HS COMT(-/-) mice also exhibited more urinary sodium excretion (COMT(-/-)
      versus wild-type: 3038+/-430 versus 659+/-102 micromol/L per 24 hours; P<0.01).
      Furthermore, DOCA/HS-induced renal oxidative stress was significantly attenuated
      in COMT(-/-) mice. COX-2-derived prostaglandins in the renal medulla promote
      sodium excretion, and dopamine stimulates medullary prostaglandin production.
      Renal medullary COX-2 expression and urinary prostaglandin E2 excretion were
      significantly higher in COMT(-/-) than in wild-type mice after DOCA/HS treatment.
      In DOCA/HS-treated COMT(-/-) mice, the COX-2 inhibitor SC-58236 reduced urinary
      sodium and prostaglandin E(2) excretion and increased systolic blood pressure
      (153+/-2 mm Hg). These studies indicate that an activated renal dopaminergic
      system attenuates the development of hypertension, at least in large part through
      activating medullary COX-2 expression/activity, and also decreases oxidative
      stress resulting from DOCA/HS.

PMID- 19770405
TI  - Regression of left ventricular mass by antihypertensive treatment: a meta
      analysis of randomized comparative studies.
AB  - Blood pressure-lowering therapy reduces left ventricular mass, but the question
      of whether differences exist among drug classes has not been fully resolved. Our
      aim was to compare the effects of diuretics, beta-blockers, calcium channel
      blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor
      blockers on left ventricular mass regression in patients with hypertension on the
      basis of prospective, randomized comparative studies. We performed meta-analyses,
      involving pooled pairwise comparisons of the drug classes and of each class
      versus other classes statistically combined, and meta-regression analyses to
      identify the determinants of the regression. The 75 relevant publications
      involved 84 pairwise comparisons and 6001 patients. Regression of left
      ventricular mass was significantly less (P=0.01) with beta-blockers (9.8%) than
      with angiotensin receptor blockers (12.5%), but none of the other analyzable
      pairwise comparisons between drug classes revealed significant differences
      (P>0.10). In addition, beta-blockers showed less regression than the other 4
      classes statistically combined (P<0.01), and regression was more pronounced with
      angiotensin receptor blockers versus the others (P<0.01). In multivariable meta
      regression analysis on all of the treatment arms, beta-blocker treatment was a
      significant and negative predictor of the regression (-3.6%; P<0.01), but this
      was not the case for the other drug classes, including angiotensin receptor
      blockers. In conclusion, beta-blockers show less regression of left ventricular
      mass, whereas angiotensin receptor blockers may induce larger regression. The
      inferiority of beta-blockers appears to be more convincing than the superiority
      of angiotensin receptor blockers.

PMID- 19770406
TI  - Prenatal dexamethasone exposure does not alter blood pressure and nephron number
      in the young adult marmoset monkey.
AB  - The influence of prenatal factors on the development of arterial hypertension has
      gained considerable interest in recent years. Prenatal dexamethasone exposure was
      found to induce hypertension and to alter nephron number and size in rodents and
      sheep. However, it is not clear whether these findings are applicable to nonhuman
      primates. Thus, we examined the effects of prenatal dexamethasone treatment on
      blood pressure (BP) and nephron number in marmoset monkeys. Fifty-two marmosets
      were allotted to 3 groups according to the gestational stage during which their
      mothers were exposed to oral 5-mg/kg dexamethasone for 7 days (gestation period:
      20 weeks): (1) the early dexamethasone group at week 7; (2) the late
      dexamethasone group at week 13; and (3) the control group. BP was determined by
      telemetric (n=12) or cuff measurements (n=30), along with cystatin C,
      proteinuria, and body weight. All of the animals were euthanized at the age of 24
      months, and glomerular number and volume were determined. Prenatal exposure to
      dexamethasone did not lead to a significant difference between the groups with
      regard to BP, kidney morphology and function, or body weight. BP correlated
      significantly with body weight, relative kidney weight, and mean glomerular
      volume and the body weight with the glomerular volume regardless of dexamethasone
      treatment. In conclusion, prenatal exposure to dexamethasone in marmosets does
      not, in contrast to other mammals studied, result in hypertension or changes in
      kidney morphology. Our data support the role of body weight as a predictor of
      elevated glomerular volume and BP development rather than prenatal dexamethasone
      exposure.

PMID- 19770408
TI  - Images in cardiovascular medicine. Real-time 3-dimensional transesophageal
      echocardiography imaging: adult patent ductus arteriosus before and after
      transcatheter closure.

PMID- 19770407
TI  - Pressure-induced vascular oxidative stress is mediated through activation of
      integrin-linked kinase 1/betaPIX/Rac-1 pathway.
AB  - High blood pressure induces a mechanical stress on vascular walls and evokes
      oxidative stress and vascular dysfunction. The aim of this study was to
      characterize the intracellular signaling causing vascular oxidative stress in
      response to pressure. In carotid arteries subjected to high pressure levels, we
      observed not only an impaired vasorelaxation, increased superoxide production,
      and NADPH oxidase activity, but also a concomitant activation of Rac-1, a small G
      protein. Selective inhibition of Rac-1, with an adenovirus carrying a dominant
      negative Rac-1 mutant, significantly reduced NADPH oxidase activity and oxidative
      stress and, more importantly, rescued vascular function in carotid arteries at
      high pressure. The analysis of molecular events associated with
      mechanotransduction demonstrated at high pressure levels an overexpression of
      integrin-linked kinase 1 and its recruitment to plasma membrane interacting with
      paxillin. The inhibition of integrin-linked kinase 1 by small interfering RNA
      impaired Rac-1 activation and rescued oxidative stress-induced vascular
      dysfunction in response to high pressure. Finally, we showed that betaPIX, a
      guanine-nucleotide exchange factor, is the intermediate molecule recruited by
      integrin-linked kinase 1, converging the intracellular signaling toward Rac-1
      mediated oxidative vascular dysfunction during pressure overload. Our data
      demonstrate that biomechanical stress evoked by high blood pressure triggers an
      integrin-linked kinase 1/betaPIX/Rac-1 signaling, thus generating oxidative
      vascular dysfunction.

PMID- 19770409
TI  - Letter by Bachhuber and Lott regarding article, "Characteristics of children
      hospitalized with infective endocarditis".

PMID- 19770412
TI  - Computerized decision support for the cardiovascular clinician: applications for
      venous thromboembolism prevention and beyond.

PMID- 19770411
TI  - Cardiovascular effects of noncardiovascular drugs.

PMID- 19770413
TI  - Images in cardiovascular medicine. Multiple coronary arteriovenous fistulas to
      the coronary sinus with an unruptured coronary sinus aneurysm and restrictive
      coronary sinus opening to the right atrium.

PMID- 19770414
TI  - Sedation management in Australian and New Zealand intensive care units: doctors'
      and nurses' practices and opinions.
AB  - OBJECTIVE: To explore the use of sedatives and analgesics, tools for scoring
      level of sedation, sedation and pain protocols, and daily interruptions in
      sedation in Australian and New Zealand intensive care units and to examine
      doctors' and nurses' opinions about the sedation management of critically ill
      patients. METHODS: A cross-sectional Internet-based survey design was used. In
      total, 2146 members of professional critical care organizations in Australia and
      New Zealand were e-mailed the survey during a 4-month period in 2006 through
      2007. RESULTS: Of 348 members (16% response rate) who accessed the survey, 246
      (71%) completed all sections. Morphine, fentanyl, midazolam, and propofol were
      the most commonly used medicines. Newer medicines, such as dexmedetomidine and
      remifentanil, and inhalant medications, such as nitrous oxide and isoflurane,
      were rarely used by most respondents. Respondents used protocols to manage
      sedatives (54%) and analgesics (51%), and sedation assessment tools were
      regularly used by 72%. A total of 62% reported daily interruption of sedation;
      23% used daily interruption for more than 75% of patients. A disparity was
      evident between respondents' opinions on how deeply patients were usually sedated
      in practice and how deeply patients should ideally be sedated. CONCLUSIONS: Newer
      medications are used much less than are traditional sedatives and analgesics.
      Sedation protocols are increasingly used in Australasia, despite equivocal
      evidence supporting their use. Similarly, daily interruption of sedation is
      common in management of patients receiving mechanical ventilation. Research is
      needed to explore contextual and personal factors that may affect sedation
      management.

PMID- 19770415
TI  - Spontaneous spinal subdural hematoma: Case study.
AB  - Spinal cord hematomas are remarkably uncommon. Even more rare are spontaneous
      spinal subdural hematomas without underlying pathological changes. In some
      patients, compression of the spinal cord by spinal subdural hematoma has led to
      acute paraplegia. Spontaneous spinal subdural hematomas occur most often in the
      thoracic spine and are manifested by sudden back pain that radiates to the upper
      or lower extremities or to the trunk and variable degrees of motor, sensory, and
      autonomic disturbances. Clinicians should consider spontaneous spinal subdural
      hematoma when patients who are taking anticoagulants report back or radicular
      pain and the development of paraparesis, because early diagnosis is essential for
      preventing irreversible paralysis. Diagnosis of spontaneous spinal subdural
      hematoma requires prompt radiological assessment; magnetic resonance imaging is
      the preferred method. Treatment includes emergent decompressive laminectomy and
      evacuation of the hematoma to prevent or minimize permanent neurological damage
      caused by spinal cord compression, ischemia, and spinal cord injury.

PMID- 19770417
TI  - Completion of radiotherapy for local and regional head and neck cancer in
      medicare.
AB  - OBJECTIVE: To identify factors associated with interruption or early
      discontinuation of treatment in patients receiving radiotherapy for head and neck
      cancer, because it is believed that such treatment interruption or early
      discontinuation increases the risk of disease relapse and adversely influences
      survival. DESIGN, SETTING, AND PATIENTS: Using the Surveillance, Epidemiology,
      and End Results (SEER)-Medicare linked database, we identified Medicare
      beneficiaries 66 years or older who were diagnosed as having local or regional
      head and neck cancer from January 1, 1997, through December 31, 2003. For each
      case, we calculated the timing and duration of radiotherapy using Medicare claims
      data. We then performed logistic regression analyses to estimate the association
      between tumor and clinical characteristics and early discontinuation of and/or
      interruptions in radiotherapy. MAIN OUTCOME MEASURE: Completion of uninterrupted
      radiotherapy. RESULTS: A substantial proportion of patients (39.8% overall) had
      interruptions in radiotherapy and/or incomplete therapy. Altogether, 70.4% of
      surgical patients completed radiotherapy with no interruptions compared with
      52.0% of nonsurgical patients (chi(2) = 78.17; P < .001). Surgery was associated
      with an increased likelihood of completing uninterrupted radiotherapy for all
      tumor sites. Comorbidity, chemotherapy, and regional disease were all associated
      with a decreased likelihood of completing radiotherapy at a subset of sites.
      CONCLUSIONS: Failure to complete uninterrupted radiotherapy is common among
      Medicare enrollees with head and neck cancer. Surgery before radiotherapy is
      associated with an increased likelihood of completing radiotherapy. At a subset
      of sites, chemotherapy is associated with a decreased likelihood of completing
      radiotherapy. Further research is needed to identify factors associated with
      noncompletion of radiotherapy among nonsurgical patients and patients who receive
      chemotherapy.

PMID- 19770416
TI  - Comparison of clinical and pathological staging in head and neck squamous cell
      carcinoma: results from Intergroup Study ECOG 4393/RTOG 9614.
AB  - OBJECTIVES: To compare the results of clinical and pathological staging for a
      large cohort of patients with head and neck squamous cell carcinoma (HNSCC) and
      to examine patterns and ramifications of the disparity between staging methods.
      DESIGN: Prospective inception cohort (median follow-up, 7 years). SETTING: Multi
      institutional cooperative group study (Eastern Cooperative Oncology Group
      4393/Radiation Therapy Oncology Group 9614) involving 17 academic medical
      centers. PATIENTS: A total of 560 patients with new-onset or recurrent HNSCC
      enrolled during a 7-year period. INTERVENTIONS: Surgical resection with curative
      intent with or without adjuvant or previous radiotherapy or chemotherapy. MAIN
      OUTCOME MEASURES: Clinical staging and pathological staging and the component TN
      tumor categories were compared with overall and disease-specific survival.
      Association of survival with staging was derived by means of the proportional
      hazards model. RESULTS: Of the 501 cases in which both clinical and pathological
      staging was available, a disparity was found between at least 1 component tumor
      category assigned by the 2 methods in almost 50% of cases. Both methods showed a
      strong association of stage with overall survival for the cohort at large.
      However, pathological nodal category was a superior predictor (P < .001 vs P =
      .005), whereas there was an advantage to pathological tumor category in
      predicting disease-specific survival (P = .01). CONCLUSIONS: Both staging methods
      are useful in predicting survival, whereas information gained at neck dissection
      regarding nodal metastases provides some refinement in prognostic results. These
      findings demonstrate the need for enhanced methods of tumor assessment and
      apparent benefit of data gathered at neck dissection for accurate disease
      assessment and stratification.

PMID- 19770419
TI  - Neck dissection planning based on postchemoradiation computed tomography in
      patients with head and neck cancer.
AB  - OBJECTIVES: To determine what findings on postchemoradiation (post-CRT) neck
      computed tomography (CT) may predict removal of the internal jugular vein (IJV)
      or sternocleidomastoid muscle (SCM) and to examine whether pretreatment CT had
      any bearing on the ultimate posttreatment neck dissection with regard to the IJV
      and SCM. DESIGN: Retrospective review of CT, intraoperative, and pathologic
      findings. SETTING: Tertiary care academic medical center. PATIENTS: Thirty-four
      patients who underwent 43 planned post-CRT hemi-neck dissections for pretreatment
      N2 or greater disease. RESULTS: Of the 43 neck dissections, 39 (91%) were
      selective neck dissections, 2 (5%) were modified radical dissections, and 2 (5%)
      were radical neck dissections. The IJV was removed in 6 of the 39 selective neck
      dissections (15%), in 1 of the 2 modified radical dissections, and in both of the
      2 radical neck dissections. The SCM was removed in the 2 modified radical
      dissections and 2 radical neck dissections. The IJV was removed in 7 of the 9
      dissections (78%) in which the IJV was abnormal on preoperative CT (filling
      defect or thrombosed) vs 2 of the 34 dissections (6%) with a normal IJV on CT (P
      < .001; positive predictive value, 78%; negative predictive value, 94%). The SCM
      was removed in 4 of the 11 dissections (36%) in which the tissue plane between
      the carotid sheath and the SCM was indistinct on CT vs 0 of the 32 dissections
      with a radiographically normal SCM tissue plane (P = .003; positive predictive
      value, 36%; negative predictive value, 100%). In 27 patients with pre-CRT CTs for
      comparison, the IJV normalized in 3 of the 8 patients (38%) with an abnormal IJV
      on pre-CRT CT, and the tissue plane around the SCM normalized in 15 of the 24
      patients (63%) with an indistinct tissue plane on pre-CRT CT. CONCLUSIONS:
      Filling defects or thrombosis of the IJV is highly predictive of need for removal
      intraoperatively, which may affect planning especially in bilateral neck
      dissections in which an effort may be made to preserve at least 1 vein. Presence
      of a clear tissue plane between the SCM and carotid sheath predicts the ability
      to preserve this muscle. Changes in the status of the IJV and SCM seen on CT that
      occur as a result of CRT may make preservation of these structures more feasible,
      even in patients with advanced neck disease.

PMID- 19770418
TI  - A phase 2 trial of surgery with perioperative INGN 201 (Ad5CMV-p53) gene therapy
      followed by chemoradiotherapy for advanced, resectable squamous cell carcinoma of
      the oral cavity, oropharynx, hypopharynx, and larynx: report of the Southwest
      Oncology Group.
AB  - OBJECTIVE: To assess the feasibility of treating patients with high-risk stage
      III and IV squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx,
      and larynx with perioperative adenovirus-p53 (INGN 201) gene therapy along with
      surgery and chemoradiotherapy. DESIGN AND SETTING: A phase 2 study in a multi
      institutional setting within the Southwest Oncology Group. PATIENTS: Thirteen
      individuals who met the following entry criteria: newly diagnosed, previously
      untreated squamous cell carcinoma of the oral cavity, oropharynx, larynx, or
      hypopharynx; selected stage III or IV disease without distant metastases; and
      surgically resectable disease. INTERVENTIONS: Surgery, perioperative INGN 201
      gene therapy, and postoperative chemoradiotherapy. MAIN OUTCOME MEASURES: Overall
      patient status, tumor status, adverse effects, accrual rate, and percentage of
      patients successfully receiving the required doses of INGN 201. RESULTS: All 13
      patients received surgery and perioperative INGN 201 injections in the primary
      tumor bed and the ipsilateral neck. In addition, 3 patients received injections
      in the contralateral neck. Three patients did not receive chemoradiotherapy. One
      patient had a grade 2 fistula of the oral cavity. Of the 10 patients with
      evaluable data, 2 experienced grade 4 adverse events, 1 owing to hypokalemia,
      hyponatremia, vomiting, leukopenia, and neutropenia and 1 owing to increased
      aspartate aminotransferase and alanine aminotransferase levels. Seven other
      patients experienced grade 3 adverse events. The estimate of 1-year progression
      free survival is 92%. CONCLUSIONS: This trial demonstrated the feasibility of
      handling and delivering a very complex gene vector safely in multiple cooperative
      group institutions without significant incident. Intraoperative INGN 201 gene
      therapy is technically feasible, but it has many logistical problems when
      performed in a multi-institutional setting. Regulatory requirements might have
      hindered accrual in this multi-institutional setting. Disease control seems to be
      promising; however, no definitive conclusion can be made with this small sample
      size. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00017173.

PMID- 19770420
TI  - Prediction of simultaneous esophageal lesions in head and neck squamous cell
      carcinoma: a multivariate analysis.
AB  - OBJECTIVE: To evaluate the frequency of concomitant esophageal lesions detected
      by esophagoscopy in squamous cell carcinoma (SCC) in the head and neck (HNSCC)
      and to identify the risk factors. DESIGN: Retrospective medical record analysis.
      SETTING: Regional hospital. PATIENTS: From March 2000 to March 2006, 118 patients
      with HNSCC had undergone esophagoscopy as part of the disease workup. Three
      patients had double head and neck primary tumors. Sixty-five patients also
      underwent chromoendoscopy with Lugol's iodine solution. MAIN OUTCOME MEASURES:
      The incidence of simultaneous esophageal cancer diagnosed on esophagoscopy.
      Additional esophageal lesions of clinical significance discovered during
      chromoendoscopy were also evaluated. RESULTS: Clinically important esophageal
      lesions were found in 12 patients (10%)-9 carcinomas and 3 dysplastic lesions.
      Chromoendoscopy was useful in 5 of these 12 cases, detecting 3 dysplastic lesions
      not visualized by ordinary esophagogastroduodenoscopy and additional lesions in 2
      patients with esophageal carcinoma. Of the patients in whom isolated oral cavity
      SCC was considered, the incidence of synchronous esophageal lesions was only
      1.5%. Sex (P = .02), younger age (P = .04), alcohol drinking (P = .047), and
      tumor sites (P = .002) were significant predictors of synchronous esophageal
      lesions on univariate analysis. On multivariate analysis, only tumor site
      remained a significant risk factor (P = .009). CONCLUSIONS: Clinically important
      esophageal lesions rarely coexists with oral cavity SCC, for which the benefit of
      routine esophagogastroduodenoscopy is questionable. Chromoendoscopy enhances the
      identification of early but clinically important esophageal abnormalities if
      esophagoscopy is performed for SCC in the larynx, hypopharynx, and oropharynx.

PMID- 19770421
TI  - Oropharyngoplasty with template-based reconstruction of oropharynx defects.
AB  - OBJECTIVE: To determine if oropharyngoplasty using a Gehanno technique of
      superior constrictor velopharyngoplasty, base of tongue mounding, and primary
      hypopharyngeal closure in combination with template-based revascularized free
      tissue transfer is effective for reconstruction of the oropharyngeal defect.
      DESIGN: Prospective case series. SETTING: Tertiary care academic medical center.
      PATIENTS: The study population comprised 25 patients (21 men and 4 women; mean
      age, 55.3 years) presenting from January 1998 to January 2001 with oropharyngeal
      squamous cell carcinoma. A comparison was performed based on the percentage of
      resection of the soft palate (group 1, < or =50% palate; group 2, >50% palate).
      INTERVENTIONS: Of the 25 patients, 24 (96%) received radiotherapy. The donor
      sites were radial forearm for 23 of 25 patients (92%) and lateral arm for 2 of 25
      patients (8%). The mean area was 92 cm(2) (range, 25-150 cm(2)), and the mean
      length of the velopharyngoplasty component of the oropharyngoplasty was 2.15 cm
      (range, 1-3 cm). MAIN OUTCOME MEASURES: Gastrostomy tube dependence, major and
      minor complications, time to oral intake, speech and swallowing assessment, and
      quality-of-life assessment. RESULTS: Of the 25 patients, 2 (8%) remain
      gastrostomy dependent; 6 (24%) developed major complications; and 7 (28%)
      developed minor complications. Speech in both groups 1 and 2 was considered
      understandable most of the time, with occasional repetition. The group 1 patient
      with a median assessment score could eat a solid diet without restriction of
      place or person, whereas the group 2 patient with a median assessment score could
      eat a soft, moist diet with selected persons in selected places. CONCLUSION:
      Integration of oropharyngoplasty with template-based revascularized free tissue
      transfer produced speech results that were independent of palate defect size, and
      swallow function test results were similar to other published reconstructive
      techniques.

PMID- 19770422
TI  - Expression of fibroblast growth factor binding protein in head and neck cancer.
AB  - OBJECTIVES: To characterize the expression of fibroblast growth factor binding
      protein (FGF-BP) messenger RNA (mRNA) in head and neck squamous cell carcinoma
      (HNSCC) and to study the association of FGF-BP with vascularity. DESIGN: The
      expression of FGF-BP mRNA in HNSCC was studied in 35 primary and 8 metastatic
      HNSCC specimens and 7 control tissues using in situ hybridization and reverse
      transcriptase-polymerase chain reaction (RT-PCR). Microvessels in tumor specimens
      were identified with endothelial cell markers (von Willebrand factor [vWF] and
      CD34-specific antibodies). Correlates between FGF-BP and microvessel counts were
      evaluated statistically. SETTING: University of Minnesota Hospitals and Clinics.
      PATIENTS: Forty-two surgically treated patients with HNSCC. INTERVENTIONS: The
      patients were routinely treated in the study hospitals and clinics. MAIN OUTCOME
      MEASURES: The expression of FGF-BP and angiogenesis in tumors were evaluated.
      RESULTS: In situ hybridization and RT-PCR demonstrated that FGF-BP mRNA
      transcripts were expressed in 34 of 35 primary HNSCC specimens and 5 of 8
      metastatic tumor specimens but not in adjacent control tissues. The microvessel
      counts in HNSCC specimens were closely related to the expression level of FGF-BP
      (P < .001). CONCLUSION: The expression of FGF-BP is statistically linked to the
      angiogenesis of HNSCC, suggesting that FGF-BP participates in the angiogenesis of
      HNSCC.

PMID- 19770423
TI  - Bilateral cochlear implantation in children with anomalous cochleovestibular
      anatomy.
AB  - OBJECTIVE: To outline clinical experience with bilateral cochlear implantation in
      children with cochleovestibular anomalies. DESIGN: A prospective cohort study
      with a mean follow-up of 12 months. SETTING: An academic, pediatric, tertiary
      referral center. PATIENTS: All eligible children were prospectively recruited
      from January 1, 2007, through October 31, 2008. Ten children aged 9 to 33 months
      who had congenital inner ear malformations, including common cavity, incomplete
      partition, and cochleovestibular hypoplasia, participated. INTERVENTIONS:
      Bilateral cochlear implantation was performed sequentially with an
      interimplantation delay greater than 2 years in 7 children and less than 1 year
      in 1 child. Bilateral simultaneous implantation was performed in 2 children. MAIN
      OUTCOME MEASURES: Complications, hearing outcomes, and balance outcomes. RESULTS:
      All children underwent successful implantation. Five children had a perilymph
      "gusher" (on 1 side only), and there were no other complications. All children
      had 22 active electrodes bilaterally and achieved speech reception. All 8
      children who underwent closed-set speech perception testing scored above 75%, and
      5 of the 7 children who underwent open-set testing achieved scores above 75%.
      Despite variable vestibular function before bilateral implantation, no prolonged
      imbalance occurred, although 3 children (30%) had transient unsteadiness for up
      to 2 weeks after the second implantation. CONCLUSIONS: Bilateral cochlear
      implantation was performed safely and successfully in children with a spectrum of
      bilaterally anomalous cochleovestibular anatomy. Hearing outcomes suggest that
      these children should not be excluded from undergoing bilateral implantation.
      This study provides guidance on candidacy issues, surgical decision making, and
      surgical techniques in this group.

PMID- 19770424
TI  - An investigation of upper airway changes associated with mandibular advancement
      device using sleep videofluoroscopy in patients with obstructive sleep apnea.
AB  - OBJECTIVE: To quantitatively evaluate the effects of the mandibular advancement
      device (MAD) on changes in the upper respiratory tract during sleep using sleep
      videofluoroscopy (SVF) in patients with obstructive sleep apnea (OSA). DESIGN:
      Retrospective analysis. SETTING: Academic tertiary referral center. PATIENTS:
      Seventy-six patients (68 men and 8 women) who were treated with the MAD for OSA
      were included from September 1, 2005, through August 31, 2008. INTERVENTION: All
      patients underwent nocturnal polysomnography and SVF before and at least 3 months
      after receipt of the custom-made MAD. Sleep videofluoroscopy was performed before
      and after sleep induction and was analyzed during 3 states of awakeness,
      normoxygenation sleep, and desaturation sleep. MAIN OUTCOME MEASURES: Changes in
      the length of the soft palate, retropalatal space, retrolingual space, and angle
      of mouth opening were evaluated during sleep events with or without the MAD.
      RESULTS: Without the MAD, the length of the soft palate and the angle of mouth
      opening increased during sleep events, especially in desaturation sleep, compared
      with the awake state. The retropalatal space and retrolingual space became much
      narrower during sleep compared with the awake state. The MAD had marked effects
      on the length of the soft palate, retropalatal space, retrolingual space, and
      angle of mouth opening. The retropalatal space and retrolingual space were
      widened, and the length of the soft palate was decreased. The MAD kept the mouth
      closed. CONCLUSIONS: Sleep videofluoroscopy showed dynamic upper airway changes
      in patients with OSA, and the MAD exerted multiple effects on the size and
      configuration of the airway. Sleep videofluoroscopy demonstrated the mechanism of
      action of the MAD in patients with OSA. The MAD increased the retropalatal and
      retrolingual spaces and decreased the length of the soft palate and the angle of
      mouth opening, resulting in improvement of OSA.

PMID- 19770426
TI  - Mandibular thickness measurements in young dentate adults.
AB  - OBJECTIVE: To measure thicknesses in clinical landmark areas of the dentate
      mandibles of young men and women. DESIGN: Using standard radiologic software, we
      obtained mean (SD) thickness measurements at the inferior or posterior borders of
      the mandible at the following 7 surgically useful sites: (1) the symphysis, (2) a
      point halfway between the symphysis and the mental nerve, (3) the mental nerve,
      (4) a point halfway between the mental nerve and the facial artery notch, (5) the
      facial artery notch, (6) the angle vertex, and (7) the ramus-condylar neck
      border. SETTING: University hospital. PATIENTS: A total of 150 dentate men and 75
      dentate women aged 18 to 30 years who had undergone computed tomography of the
      head and neck region during the period of December 20, 2006 to February 20, 2007.
      MAIN OUTCOME MEASURE: Thicknesses of 7 mandibular sites. RESULTS: Mean (SD)
      thicknesses at the 7 mandibular sites were as follows: symphysis, 14.03 (1.53) mm
      for men and 13.21 (1.46) mm for women; halfway between the symphysis and the
      mental nerve, 11.17 (1.37) mm for men and 10.00 (1.08) mm for women; mental
      nerve, 9.48 (1.28) mm for men and 8.72 (1.00) mm for women; halfway between the
      mental nerve and the facial artery notch, 10.33 (1.24) mm for men and 9.45 (0.92)
      mm for women; facial artery notch, 7.27 (0.82) mm for men and 7.10 (0.88) mm for
      women; angle vertex, 5.42 (0.90) mm for men and 5.39 (0.66) mm for women; and
      ramus-condylar neck border, 5.90 (0.86) mm for men and 5.85 (0.71) mm for women.
      CONCLUSIONS: Clinical landmark areas in young dentate mandibles have mean
      thicknesses with limited SDs. The thickness measurements obtained at the sites in
      this study provide practical reference information for mandibular reconstruction
      and bicortical screw length estimation.

PMID- 19770425
TI  - First-choice treatment in mild to moderate obstructive sleep apnea: single-stage,
      multilevel, temperature-controlled radiofrequency tissue volume reduction or
      nasal continuous positive airway pressure.
AB  - OBJECTIVE: To compare the efficacy of single-stage, multilevel, temperature
      controlled radiofrequency tissue volume reduction (TCRFTVR) for the soft palate
      and base of the tongue with that of nasal continuous positive airway pressure
      (CPAP) in primary treatment of mild to moderate obstructive sleep apnea. DESIGN:
      A prospective nonrandomized clinical study. SETTING: Tertiary care referral
      center. PATIENTS: Data from 47 patients with mild to moderate obstructive sleep
      apnea treated between January 1, 2003, and October 31, 2006, were reviewed.
      INTERVENTIONS: Twenty-six patients underwent TCRFTVR and 21 underwent nasal CPAP
      as a primary treatment modality. MAIN OUTCOME MEASURES: Baseline and 12-month
      posttreatment measurements using the Epworth Sleepiness Scale and polysomnography
      were compared. RESULTS: The baseline characteristics of the groups were not
      significantly different. Both methods showed meaningful results for the Epworth
      Sleepiness Scale and polysomnography variables 12 months after treatment compared
      with baseline measurements. The results were not significantly different in the
      posttreatment intergroup comparisons. Treatment success rates were 52.4% for
      nasal CPAP and 53.8% for TCRFTVR (P = .92). CONCLUSION: Similar comparison
      results with nasal CPAP in objective and subjective variables make single-stage,
      multilevel TCRFTVR a good alternative in primary treatment of mild to moderate
      obstructive sleep apnea.

PMID- 19770427
TI  - Surgical management of drooling: a meta-analysis.
AB  - OBJECTIVE: To review and assess the current published literature regarding the
      efficacy of surgical management of sialorrhea in pediatric patients. DATA
      SOURCES: The MEDLINE database was systematically reviewed for articles reporting
      on the use of surgical procedures to treat sialorrhea published from January 1,
      1963, to November 30, 2008. STUDY SELECTION: Inclusion criteria included presence
      of data on the success of surgical treatment of sialorrhea, English language,
      sample size greater than 5, and presentation of extractable data regarding the
      subjective success of surgical management of sialorrhea. DATA EXTRACTION: Data
      regarding demographic characteristics of study participants, follow-up duration,
      subjective success rates, and number and type of complications were extracted by
      blinded reviewers. DATA SYNTHESIS: A total of 325 studies were identified on
      initial search. Abstract review reduced the sample to 46. Cross-referencing
      yielded an additional 4 articles, resulting in the final sample of 50 articles.
      Forty-seven studies were case series (Centre for Evidence-Based Medicine level 4
      evidence), 2 were cohort studies (level 2), and 1 was a prospective cohort study
      (level 1b). Median sample size was 18 (range, 5-181), and median follow-up
      duration was 8.1 months (range, 0.1-50 months). Subjective success was reported
      in more than 50% of patients in 49 of 50 studies. Random-effects modeling
      estimated the overall subjective success rate for all procedures to be 81.6% (95%
      confidence interval, 77.5%-85.7%; P < .001). Bilateral submandibular gland
      excision and parotid duct rerouting appeared to have the highest subjective
      success rates at 87.8% (k = 8 studies; 95% confidence interval, 80.5%-95.1%; P
      <.001), and 4-duct ligation was the lowest at 64.1% (4 studies; 27.6%-100%; P =
      .001). CONCLUSIONS: Most evidence regarding surgical outcomes of sialorrhea
      management is low quality and heterogeneous. Despite this, most patients
      experience a subjective improvement following surgical treatment.

PMID- 19770428
TI  - Management of nasolabial cysts by transnasal endoscopic marsupialization.
AB  - OBJECTIVE: To evaluate hospitalization rates and duration of surgery associated
      with transnasal endoscopic marsupialization compared with sublabial excision in
      treating nasolabial cysts. DESIGN: Retrospective clinical series. SETTING: Large
      urban community hospital. PATIENTS: Consecutive sample of 57 patients with
      nasolabial cysts treated from January 1, 2000, to February 29, 2008.
      INTERVENTIONS: Sublabial excision in 23 patients (sublabial group) and transnasal
      endoscopic marsupialization in 34 patients (transnasal group). Among 57 patients,
      47 underwent preoperative computed tomography. MAIN OUTCOME MEASURES: History,
      clinical presentation, preoperative condition, histopathologic findings,
      treatment, complications, and outcomes. RESULTS: The mean duration of surgery was
      91.3 minutes in the sublabial group and 29.5 minutes in the transnasal group (P =
      .003). The hospitalization rate was 100% (23 of 23) in the sublabial group and
      59% (20 of 34) in the transnasal group (P < .001). The medical costs were
      significantly lower in the transnasal group than in the sublabial group (P =
      .002). The follow-up period ranged from 6 to 85 months. Neither group of patients
      experienced any major complications or recurrences during the follow-up period.
      CONCLUSION: Transnasal endoscopic marsupialization is an effective treatment for
      nasolabial cysts, is less costly, and has fewer complications than sublabial
      excision.

PMID- 19770429
TI  - Effects of synchronous nasal surgery on posttonsillectomy hemorrhage.
AB  - OBJECTIVE: To evaluate the effects of synchronous nasal surgery on the rate of
      posttonsillectomy hemorrhage. DESIGN: Retrospective medical record review.
      SETTING: Military tertiary referral center. PATIENTS: Adult patients identified
      in our surgical database from June 1, 2000, through September 31, 2005, who had
      undergone tonsillectomy or uvulopalatopharyngoplasty with tonsillectomy (UPPPT)
      either alone or with synchronous nasal surgery. MAIN OUTCOME MEASURES: The rate
      of posttonsillectomy hemorrhage was reviewed in all patients who underwent
      tonsillectomy or UPPPT at our medical center, and an investigation was conducted
      to determine whether synchronous nasal surgery altered this rate. RESULTS: A
      total of 1010 patients were included in this study, with a rate of
      posttonsillectomy hemorrhage of 5.5%. A total of 204 patients underwent
      synchronous nasal surgery. No significant difference was found between the
      hemorrhage rate in patients who underwent tonsillectomy or UPPPT alone and those
      who underwent synchronous nasal surgery (6.0% and 3.9%, respectively; P = .30).
      When these patients were further divided into those undergoing UPPPT and those
      undergoing synchronous nasal surgery, no significant difference in hemorrhage
      rate was found (6.2% and 2.0%, respectively; P = .06). CONCLUSIONS: Synchronous
      nasal surgery does not appear to increase the rate of postoperative hemorrhage in
      patients who undergo tonsillectomy alone or in those who undergo UPPPT. This
      information may help persuade physicians to perform synchronous surgical
      procedures instead of staging surgical procedures. In this regard, the patient
      requires only 1 anesthetic and 1 postoperative course without the risk of
      increased postoperative hemorrhage.

PMID- 19770430
TI  - Radiology Quiz Case 1. Retropharyngeal abscess revealing a right fourth branchial
      pouch sinus.

PMID- 19770431
TI  - Radiology Quiz Case 2. Giant tonsillolith.

PMID- 19770432
TI  - Pathology Quiz Case 1. Keratocystic odontogenic tumor (KCOT).

PMID- 19770433
TI  - Pathology Quiz Case 2. Nasal chondromesenchymal hamartoma (NCMH).

PMID- 19770434
TI  - Primary leiomyosarcoma of the sphenoid sinus.

PMID- 19770435
TI  - Aryepiglottic abscess manifesting as epiglottitis.

PMID- 19770436
TI  - Vorinostat for the treatment of bullous pemphigoid in the setting of advanced,
      refractory cutaneous T-cell lymphoma.

PMID- 19770437
TI  - Tanning and increased nevus development in very-light-skinned children without
      red hair.
AB  - OBJECTIVE: To examine the relationship between tanning and nevus development in
      very-light-skinned children. DESIGN: Prospective cohort nested within a
      randomized controlled trial. Skin examinations in 3 consecutive years (2004,
      2005, and 2006) included full-body counts of nevi, skin color and tanning
      measurement using colorimetry, and hair and eye color evaluation by comparison
      with charts. Telephone interviews of parents provided sun exposure, sun
      protection, and sunburn history. SETTING: Large managed-care organization and
      private pediatric offices in the Denver, Colorado, metropolitan area.
      PARTICIPANTS: A total of 131 very-light-skinned white children without red hair
      and 444 darker-skinned white children without red hair born in Colorado in 1998.
      MAIN OUTCOME MEASURES: Full-body nevus counts at ages 6 to 8 years. RESULTS:
      Among very-light-skinned white children, geometric mean numbers of nevi for
      minimally tanned children were 14.8 at age 6 years; 18.8 at age 7 years; and 22.3
      at age 8 years. Mean numbers of nevi for tanned children were 21.2 at age 6
      years; 27.9 at age 7 years; and 31.9 at age 8 years. Differences in nevus counts
      between untanned and tanned children were statistically significant at all ages
      (P < .05 for all comparisons). The relationship between tanning and number of
      nevi was independent of the child's hair and eye color, parent-reported sun
      exposure, and skin phototype. Among darker-skinned white children, there was no
      relationship between tanning and nevi. CONCLUSIONS: Very-light-skinned children
      who tan (based on objective measurement) develop more nevi than children who do
      not tan. These results suggest that light-skinned children who develop tans may
      be increasing their risk for developing melanoma later in life.

PMID- 19770438
TI  - Youth access to artificial UV radiation exposure: practices of 3647 US indoor
      tanning facilities.
AB  - OBJECTIVE: To assess indoor tanning facility practices in a sample of facilities
      in 116 cities representing all 50 states. DESIGN: Cross-sectional study. SETTING:
      United States. PARTICIPANTS: Employees of 3647 indoor tanning facilities were
      contacted by telephone. Data collectors (ie, confederates) posed as prospective,
      fair-skinned, 15-year-old female customers who had never tanned before. MAIN
      OUTCOME MEASURES: Confederates asked respondents about their facility's practices
      related to parental consent, parental accompaniment, and allowable tanning
      session frequency. RESULTS: Approximately 87% of the facilities required parental
      consent, 14% required parental accompaniment, 5% said they would not allow the
      confederate to tan owing to her age, and 71% would allow tanning every day the
      first week of indoor tanning. In Wisconsin, which bans indoor tanning among those
      younger than 16 years, 70% of facilities would not allow the confederate to tan.
      Multivariate analyses indicated that facilities in states with a youth access law
      were significantly more likely to require parental consent (P <.001) and parental
      accompaniment (P <.001) than those in states without a youth access law. Law was
      not significantly related to allowable tanning frequency (P = .81). Conclusion We
      recommend that additional states pass youth access legislation, preferably in the
      form of bans.

PMID- 19770439
TI  - Mortality of bullous skin disorders from 1979 through 2002 in the United States.
AB  - OBJECTIVES: To identify and analyze trends in bullous disease mortality from 1979
      through 2002 in the United States. DESIGN: Retrospective population-based
      analysis. SETTING: Mortality records from the Centers for Disease Control and
      Prevention mortality database. PARTICIPANTS: Mortality records from 1979 through
      2002 for persons who died of bullous disease. MAIN OUTCOME MEASURES: Age-adjusted
      mortality rates and trends for 4 bullous disease subgroups: toxic epidermal
      necrolysis, pemphigoid, pemphigus, and epidermolysis bullosa. RESULTS: The
      overall age-adjusted (to the 2000 US standard population) annual mortality rate
      from bullous diseases of the skin was 0.103 death per 100 000. The average
      mortality from bullous disorders was 0.098 per 100 000 in 1979 through 1982 and
      remained stable at 0.099 per 100 000 during the final 4 years of the study, 1999
      through 2002. Pemphigoid had a significant increase in mortality from 1979
      through 2002, while pemphigus demonstrated a significant decrease in mortality.
      The mortality rate for toxic epidermal necrolysis was much higher among blacks
      (0.192 death per 100 000) than whites (0.025 per 100 000) (P < .001), with a
      mortality rate ratio of 7.57 (95% confidence interval, 6.97-8.21). CONCLUSIONS:
      Overall mortality from bullous diseases remained stable from 1979 through 2002,
      although an increasing mortality from pemphigoid and a decreasing mortality from
      pemphigus occurred during this period. A very large racial disparity in mortality
      from toxic epidermal necrolysis was observed.

PMID- 19770441
TI  - Psychological distress in patients with morphea and eosinophilic fasciitis.
AB  - OBJECTIVE: To examine the level of psychological distress and factors
      contributing to distress in patients with morphea or eosinophilic fasciitis.
      DESIGN: Cross-sectional study. SETTING: Dermatology outpatient clinic of a
      university hospital. PARTICIPANTS: Of 120 patients with morphea or eosinophilic
      fasciitis diagnosed between December 1, 1994, and July 15, 2007, who were
      enrolled in the study, only 74 completed questionnaires were suitable for data
      analysis. MAIN OUTCOME MEASURES: Self-reported responses on the Impact of Chronic
      Skin Diseases on Daily Life scale measure psychological distress, specifically
      anxiety and depressed mood. RESULTS: Psychological functioning was generally
      impaired in patients with skin disease, particularly among patients with
      generalized morphea and eosinophilic fasciitis. Twenty-eight patients (38%) were
      at risk of depression or anxiety. Higher levels of psychological distress were
      significantly related to greater severity of skin disease; more pain and fatigue;
      impact of disease on daily life; more perceived stigmatization; illness
      cognitions of greater helplessness; and less acceptance and less perceived social
      support. CONCLUSIONS: Physical and psychosocial aspects play a substantial role
      in the quality of life for patients with morphea. Physicians should be encouraged
      to assess the physical and psychosocial factors when treating patients with
      sclerotic skin diseases. This approach could improve quality of life and
      ultimately lead to improved dermatological treatment outcomes.

PMID- 19770440
TI  - Association of cigarette smoking but not alcohol consumption with cutaneous lupus
      erythematosus.
AB  - OBJECTIVE: To ascertain whether smoking or alcohol consumption is associated with
      lupus erythematosus (LE), because this topic is still subject to debate and part
      of the debate could be related to the fact that smoking and alcohol consumption
      are specific risk factors for cutaneous LE. DESIGN: Prospective multicenter case
      control study. SETTING: Three French university hospitals. Patients One hundred
      eight patients with LE and 216 control subjects. Intervention Standardized
      questionnaire evaluating cigarette smoking and alcohol consumption. MAIN OUTCOME
      MEASURES: The statistical significance of smoking history and alcohol consumption
      as associated risk factors for LE by estimating matched case-control odds ratios
      and their 95% confidence intervals, using multiple conditional logistic
      regression and the Breslow-Day test to investigate differences in quantities of
      cigarette and alcohol consumption. RESULTS: Of the LE patients, 73.1% smoked
      compared with 49.5% of controls, (odds ratio, 2.77; 95% confidence interval, 1.63
      4.76). There was no significant difference in alcohol consumption between LE
      patients and controls. Among the 79 LE patients who smoked, 72 (91.1%) had
      started smoking before the first manifestation of LE (mean delay between
      initiation of smoking and first signs of LE, 14.1 years). The LE patients smoked
      significantly more than controls did (11.7 vs 7.0 pack-years; P = .002). The
      prevalence of smoking among patients who met more than 4 American College of
      Rheumatology (ACR) criteria and/or with antinuclear DNA antibodies was lower than
      the prevalence in patients who met fewer than 4 ACR criteria or than the
      prevalence in controls (P < .001). CONCLUSIONS: Cigarette smoking is associated
      with LE, but alcohol consumption is not. The risk conferred by cigarette smoking
      seems highest in patients who meet fewer than 4 ACR criteria and/or who do not
      have antinuclear DNA antibodies.

PMID- 19770442
TI  - Leishmania tropica-induced cutaneous and presumptive concomitant viscerotropic
      leishmaniasis with prolonged incubation.
AB  - BACKGROUND: Leishmaniasis includes a spectrum of diseases caused by protozoan
      parasites belonging to the genus Leishmania. The disease is traditionally
      classified into visceral, cutaneous, or mucocutaneous leishmaniasis, depending on
      clinical characteristics as well as the species involved. Leishmania tropica is
      one of the causative agents of cutaneous leishmaniasis, with a typical incubation
      period of weeks to months. Observation We describe a 17-year-old Afghani girl who
      had lived in the United States for 4 years and who presented with a 6-month
      history of pretibial ulcerations, 9.1-kg weight loss, abdominal pain,
      splenomegaly, and extreme fatigue. Histopathologic examination and culture with
      isoenzyme electrophoresis speciation of her skin lesions confirmed the presence
      of L tropica. In addition, results of serum laboratory and serological studies
      were highly suggestive of concomitant visceral involvement. The patient was
      treated with a 28-day course of intravenous pentavalent antimonial compound
      sodium stibogluconate with complete resolution of her systemic signs and symptoms
      and improvement of her pretibial ulcerations. CONCLUSIONS: This is an exceptional
      case in that our patient presented with disease after an incubation period of
      years rather than the more typical weeks to months. In addition, this patient had
      confirmed cutaneous involvement, as well as strong evidence of viscerotropic
      disease caused by L tropica, a species that characteristically displays
      dermotropism, not viscerotropism.

PMID- 19770443
TI  - Interaction of topical sulfacetamide and topical dapsone with benzoyl peroxide.
AB  - BACKGROUND: A recent study demonstrated evidence of a yellow-orange discoloration
      of the skin and hair when topical dapsone gel was combined with benzoyl peroxide.
      This phenomenon had previously been observed by one of us (A.B.F.) when
      sulfasalazine was combined with benzoyl peroxide. To investigate these
      interaction phenomena, topical dapsone gel and sulfacetamide sodium lotion were
      combined with various topical acne treatments, including benzoyl peroxides,
      clindamycin phosphate, and retinoids. OBSERVATIONS: Products containing benzoyl
      peroxide produced an orange-brown discoloration when mixed with either
      sulfacetamide or dapsone. CONCLUSIONS: Knowledge of the chemical reaction between
      benzoyl peroxide and sulfacetamide and dapsone will help minimize the occurrence
      of this interaction on our patients' skin.

PMID- 19770444
TI  - Cytomegalovirus disease during severe drug eruptions: report of 2 cases and
      retrospective study of 18 patients with drug-induced hypersensitivity syndrome.
AB  - BACKGROUND: Overt cytomegalovirus (CMV) disease is a serious viral infection that
      usually occurs in immunocompromised patients but rarely in immunocompetent
      patients. Cutaneous lesions, albeit rare, occur as late systemic manifestations
      of CMV infections and are usually fatal. OBSERVATIONS: We describe 2 patients
      with drug-induced hypersensitivity syndrome (one end of a spectrum of severe drug
      eruptions) who subsequently developed cutaneous CMV ulcers at unusual sites, such
      as the trunk; this occurrence was immediately followed by gastrointestinal
      manifestations, which were fatal in 1 patient. To identify factors predictive of
      CMV disease, we retrospectively investigated the prevalence of CMV reactivation
      during drug-induced hypersensitivity syndrome in 18 patients. In this analysis,
      patients were divided into 2 groups depending on the positivity of CMV DNA in the
      blood. CONCLUSIONS: Older and male patients with antecedent high human
      herpesvirus 6 DNA loads are at risk for CMV disease irrespective of
      corticosteroid administration. A rapid reduction in white blood cell numbers is
      also predictive of the onset of CMV disease.

PMID- 19770445
TI  - The misperception that clinical trial data reflect long-term drug safety: lessons
      learned from Efalizumab's withdrawal.

PMID- 19770446
TI  - Hepatitis C virus and lichen planus: a reciprocal association determined by a
      meta-analysis.
AB  - OBJECTIVE: To explore the association between hepatitis C virus (HCV) and lichen
      planus (LP) by performing a meta-analysis of observational studies of the
      association. Data Sources Bibliographical searches were conducted in the MEDLINE,
      EMBASE, and China National Knowledge Infrastructure (CNKI) databases without any
      language limitations. Study Selection Studies were selected when the following
      criteria were met: the coexistence of a study group and a control group, the
      reliable and nonselective use of the reference standards for the diagnosis of LP
      and HCV, and the proportion of events (the prevalence of HCV in patients with LP
      or the prevalence of LP in patients with HCV). Data Extraction Three
      investigators independently assessed abstracts for relevant studies, and 2
      investigators independently reviewed all eligible studies. Data Synthesis Sixty
      three articles entailing 7 studies were included in the meta-analysis. For the
      primary outcome of prevalence of events, the meta-analysis showed that there
      existed an important association between HCV and LP. In the comparison of the
      prevalence of HCV exposure among patients with LP with that of control
      participants, the odds ratio (OR) was 5.4 (95% confidence interval [CI], 3.5
      8.3); in the prevalence of LP among patients with HCV compared with the
      prevalence among control participants, the OR was 2.5 (95% CI, 2.0-3.1). The
      subgroup analyses with geographical stratification did not show a significant
      association in studies from South Asia (P = .21), Africa (P = .15), and North
      America (P = .09), and the subgroup analyses from stratification by LP type also
      did not show a significant association in the isolated cutaneous type (P = .17).
      When strict criteria were applied, the results of sensitivity analysis remained
      robust. Conclusion Hepatitis C virus infection is associated with a statistically
      significant risk for development of LP, suggesting that the presence of either
      HCV or certain types of LP may be used as a predictive marker of the other in
      certain geographical regions.

PMID- 19770447
TI  - The blind man and the paralytic boy of lesnovo: diagnosis of borderline
      lepromatous leprosy after 660 years?

PMID- 19770448
TI  - The relationship between lichen planus and hepatitis C clarified.

PMID- 19770449
TI  - Developing healthy sun habits for life: challenges and opportunities.

PMID- 19770450
TI  - Linear pruritic eruption with onychodystrophy in a 1-year-old girl--quiz case.

PMID- 19770451
TI  - Acute onset of erythematous scalp nodules in a child--quiz case.

PMID- 19770452
TI  - Erythematous plaques involving calves--quiz case.

PMID- 19770453
TI  - Generalized blue-gray pigmentation--quiz case.

PMID- 19770454
TI  - Objectification theory and our understanding of indoor tanning.

PMID- 19770455
TI  - Transillumination as a means to differentiate melanocytic lesions based on their
      vascularity.

PMID- 19770456
TI  - Scalp dermatomyositis revisited.

PMID- 19770457
TI  - Tretinoin: an established long-term safety profile.

PMID- 19770458
TI  - Petrified ear: a complication of bluetooth headset use.

PMID- 19770459
TI  - Clear cell papulosis: a connection of clear cells to toker cells or paget
      disease.

PMID- 19770460
TI  - Bloody nipple discharge in an infant.

PMID- 19770461
TI  - Acute generalized exanthematous pustulosis caused by rifabutin.

PMID- 19770462
TI  - Cutaneous dirt-adherent disease with single apparent transverse leukonychia on
      the fingernails.

PMID- 19770463
TI  - Primary scrotal melanoma presenting as a large, amelanotic, exophytic mass.

PMID- 19770464
TI  - Evoked scale sign of tinea versicolor.

PMID- 19770465
TI  - Teaching NeuroImages: Reversible bilateral thalamic lesions in vein of Galen
      thrombosis.

PMID- 19770466
TI  - Teaching NeuroImages: Acute tetraparesis: Mind the brain.

PMID- 19770469
TI  - Baseline CSF p-tau levels independently predict progression of hippocampal
      atrophy in Alzheimer disease.
AB  - OBJECTIVE: To investigate whether baseline CSF biomarkers are associated with
      hippocampal atrophy rate as a measure of disease progression in patients with
      Alzheimer disease (AD), patients with mild cognitive impairment (MCI), and
      controls, controlling for baseline neuropsychological and MRI findings. METHODS:
      We assessed data from 31 patients with AD, 25 patients with MCI, and 19 controls
      (mean age 68 +/- 8 years; 39 [52%] female) who visited our memory clinic and had
      received serial MRI scanning (scan interval 1.7 +/- 0.7 years). At baseline, CSF
      biomarkers (amyloid beta 1-42, tau, and tau phosphorylated at threonine 181 [p
      tau]) were obtained, as well as neuropsychological data. Baseline MRI scans were
      assessed using visual rating scales for medial temporal lobe atrophy (MTA),
      global cortical atrophy, and white matter hyperintensities. Hippocampal atrophy
      rates were estimated using regional nonlinear "fluid" registration of follow-up
      scan to baseline scan. RESULTS: Stepwise multiple linear regression, adjusted for
      age and sex, showed that increased CSF p-tau levels (beta [standard error]: -0.79
      [0.35]) at baseline was independently associated with higher subsequent
      hippocampal atrophy rates (p < 0.05), together with poorer memory performance
      (0.09 [0.04]) and more severe MTA (-0.60 [0.21]). The association of memory
      function with hippocampal atrophy rate was explained by the link with diagnosis,
      because it disappeared from the model after we additionally corrected for
      diagnosis. CONCLUSIONS: Baseline CSF levels of tau phosphorylated at threonine
      181 are independently associated with subsequent disease progression, as
      reflected by hippocampal atrophy rate. This effect is independent of baseline
      neuropsychological and MRI predictors. Our results imply that predicting disease
      progression can best be achieved by combining information from different
      modalities.

PMID- 19770470
TI  - Plasma exchange for acute attacks of CNS demyelination: Predictors of improvement
      at 6 months.
AB  - BACKGROUND: Plasma exchange (PE) is used to treat severe episodes of CNS
      demyelination unresponsive to corticosteroids. Predictors of long-term response
      are not well known. METHODS: We retrospectively reviewed the medical records of
      41 patients consecutively treated by PE between January 1995 and July 2007. The
      primary outcome was improvement at 6 months after PE defined as decrease of >or=1
      point in the Expanded Disability Status Scale (EDSS) score for patients with EDSS
      <or=7.5 or 1.5 points with EDSS >or=8.0 or improvement of more than 2 lines in
      the visual acuity chart for patients with optic neuritis (ON). RESULTS: Twenty
      five patients (61%) were women, and the median age was 33 years (range 14-57
      years). Twenty-three (56%) had multiple sclerosis, 2 (5%) had clinically isolated
      syndrome, 2 (5%) had Marburg disease, 7 (17%) had acute disseminated
      encephalomyelitis, 4 (10%) had neuromyelitis optica, 2 (5%) had idiopathic ON,
      and 1 (2%) had idiopathic transverse myelitis. The median EDSS score before the
      attack was 1.0 (range 0-6.5). At PE onset, the median EDSS score was 7.0 (range
      3.0-9.5). Sixteen patients (39%) improved at discharge, and 26 (63%) improved at
      6 months. In the multivariate analysis, early initiation of PE (odds ratio [OR]
      6.29, 95% confidence interval [CI] 1.18-52.96) and improvement at discharge (OR
      7.32, 95% CI 1.21-44.38) were significantly associated with response at 6 months.
      CONCLUSIONS: Plasma exchange (PE) was associated with clinical improvement in 63%
      of patients at 6 months. Early initiation of PE and improvement at discharge were
      predictors of this response. Twelve patients (48%) who did not improve early did
      so during follow-up.

PMID- 19770468
TI  - Declining financial capacity in mild cognitive impairment: A 1-year longitudinal
      study.
AB  - OBJECTIVE: To investigate 1-year change in financial capacity in relation to
      conversion from amnestic mild cognitive impairment (MCI) to dementia. METHODS:
      Seventy-six cognitively healthy older controls, 25 patients with amnestic MCI who
      converted to Alzheimer-type dementia during the study period (MCI converters),
      and 62 patients with MCI who did not convert to dementia (MCI nonconverters) were
      administered the Financial Capacity Instrument (FCI) at baseline and 1-year
      follow-up. Performance on the FCI domain and global scores was compared within
      and between groups using multivariate repeated-measures analyses. RESULTS: At
      baseline, controls performed better than MCI converters and nonconverters on
      almost all FCI domains and on both FCI total scores. MCI converters performed
      below nonconverters on domains of financial concepts, cash transactions, bank
      statement management, and bill payment and on both FCI total scores. At 1-year
      follow-up, MCI converters showed significantly greater decline than controls and
      MCI nonconverters for the domain of checkbook management and for both FCI total
      scores. The domain of bank statement management showed a strong trend. For both
      the checkbook and bank statement domains, MCI converters showed declines in
      procedural skills, such as calculating the correct balance in a checkbook
      register, but not in conceptual understanding of a checkbook or a bank statement.
      CONCLUSIONS: Declining financial skills are detectable in patients with mild
      cognitive impairment (MCI) in the year before their conversion to Alzheimer
      disease. Clinicians should proactively monitor patients with MCI for declining
      financial skills and advise patients and families about appropriate
      interventions.

PMID- 19770471
TI  - Trends and determinants of end-of-life practices in ALS in the Netherlands.
AB  - BACKGROUND: In the Netherlands, the proportion of patients with amyotrophic
      lateral sclerosis (ALS) who choose the option of euthanasia or physician-assisted
      suicide (PAS) is relatively high (20%). The objective of this study was to
      determine which factors influence end-of-life practices in ALS and whether rates
      are changing over time. METHODS: In a cohort survey, 204 physicians and 198
      informal caregivers (response rates 75% and 80%) of patients with ALS who died
      between 2000 and 2005 filled out questionnaires of the end-of-life circumstances
      of the patient. Results were compared with those of a similar study performed
      during the period 1994-1998. RESULTS: In 2000-2005, 16.8% of the patients decided
      on euthanasia or PAS compared to 20.2% in 1994-1998. Thirty-one (14.8%) patients
      died during continuous deep sedation (CDS) in 2000-2005. Euthanasia or PAS, but
      not CDS, were significantly associated with religion not being important to the
      patient, being more educated, and dying at home. Euthanasia or PAS were not
      associated with quality of care items or symptoms of depression. Loss of function
      was similar in both groups. Informal caregivers of patients who died after
      euthanasia or PAS more frequently reported fear of choking (p = 0.003), no chance
      of improvement (p = 0.001), loss of dignity (p = 0.02), being dependent on others
      (p = 0.002), and fatigue (p = 0.018) as reasons for shortening life. Hopelessness
      was associated with euthanasia or PAS, as with CDS. CONCLUSION: The frequency of
      euthanasia or physician-assisted suicide (PAS) in amyotrophic lateral sclerosis
      (ALS) appeared stable over time and 1 in 7 patients died during CDS. CDS is
      relatively common in ALS, but appears to have other determinants than euthanasia
      or PAS. Subjective factors may be important in explaining euthanasia or PAS in
      ALS.

PMID- 19770472
TI  - Expanding the clinical and neuroradiologic phenotype of primary microcephaly due
      to ASPM mutations.
AB  - OBJECTIVE: To determine the spectrum of clinical, neuropsychological, and
      neuroradiologic features in patients with autosomal recessive primary
      microcephaly (MCPH) due to ASPM gene mutations. METHODS: ASPM was sequenced in 52
      unrelated MCPH probands. In patients with ASPM mutations, we evaluated the
      clinical phenotype, cognition, behavior, brain MRI, and family. RESULTS: We found
      homozygous or compound heterozygous ASPM loss-of-function mutations in 11 (22%)
      probands and 5 siblings. The probands harbored 18 different mutations, of which
      16 were new. Microcephaly was severe after 1 year of age in all 16 patients,
      although in 4 patients the occipital-frontal circumference (OFC) at birth was
      decreased by only 2 SD. The OFC Z score consistently decreased after birth. Late
      onset seizures occurred in 3 patients and significant pyramidal tract involvement
      in 1 patient. Intellectual quotients ranged from borderline-normal to severe
      mental retardation. Mild motor delay was noted in 7/16 patients. Language
      development was delayed in all patients older than 3 years. Brain MRI (n = 12)
      showed a simplified gyral pattern in 9 patients and several malformations
      including ventricle enlargement (n = 7), partial corpus callosum agenesis (n =
      3), mild cerebellar hypoplasia (n = 1), focal cortical dysplasia (n = 1), and
      unilateral polymicrogyria (n = 1). Non-neurologic abnormalities consisted of
      short stature (n = 1), idiopathic premature puberty (n = 1), and renal dysplasia
      (n = 1). CONCLUSIONS: We provide a detailed description of features associated
      with ASPM mutations. Borderline microcephaly at birth, borderline-normal
      intellectual efficiency, and brain malformations can occur in ASPM-related
      primary hereditary microcephaly.

PMID- 19770473
TI  - Randomized, controlled trial of telcagepant for the acute treatment of migraine.
AB  - BACKGROUND: The neuropeptide calcitonin gene-related peptide (CGRP) plays a key
      role in migraine pathophysiology. In this large phase 3 clinical trial, we sought
      to confirm the efficacy of telcagepant, the first orally bioavailable CGRP
      receptor antagonist. METHODS: Adults with migraine with or without aura
      (International Headache Society criteria) treated a moderate or severe attack
      with oral telcagepant 50 mg (n = 177), 150 mg (n = 381), 300 mg (n = 371), or
      placebo (n = 365) in a randomized, double-blind trial. The 5 co-primary endpoints
      were pain freedom, pain relief, and absence of photophobia, absence of
      phonophobia, and absence of nausea, all at 2 hours postdose. The key secondary
      endpoint was 2-24 hour sustained pain freedom. The prespecified primary efficacy
      analyses evaluated the 150 mg and 300 mg groups; the 50-mg group was included on
      an exploratory basis to further characterize the dose response but was not
      prespecified for analysis. Tolerability was assessed by adverse experience
      reports. RESULTS: Telcagepant 300 mg was more effective (p <or= 0.001) than
      placebo on all primary endpoints and the key secondary endpoint, as was
      telcagepant 150 mg (p <or= 0.05). Telcagepant 300 mg showed a slight numeric
      advantage over telcagepant 150 mg on most measures. Telcagepant 50 mg values were
      numerically intermediate between placebo and telcagepant 150 mg and 300 mg. The
      percentages of patients with adverse experiences were 32.2% for telcagepant 50
      mg, 32.0% for telcagepant 150 mg, 36.2% for telcagepant 300 mg, and 32.2% for
      placebo. CONCLUSIONS: This study confirmed previous findings that telcagepant 300
      mg was effective at relieving pain and other migraine symptoms at 2 hours and
      providing sustained pain freedom up to 24 hours. In this study, telcagepant 150
      mg was also effective. Telcagepant was generally well tolerated.

PMID- 19770474
TI  - Gray matter changes related to chronic posttraumatic headache.
AB  - BACKGROUND: Although up to 15% of patients with whiplash injury develop chronic
      headache, the basis and mechanisms of this posttraumatic headache are not well
      understood. METHODS: Thirty-two patients with posttraumatic headache following
      whiplash injury were investigated within 14 days after the accident and again
      after 3 months using magnetic resonance-based voxel-based morphometry. Twelve
      patients developed chronic headache lasting longer than 3 months and were studied
      a third time after 1 year. RESULTS: Patients who developed chronic headache
      revealed decreases in gray matter in the anterior cingulate and dorsolateral
      prefrontal cortex after 3 months. These changes resolved after 1 year, in
      parallel to the cessation of headache. The same patients who developed chronic
      headache showed an increase of gray matter in antinociceptive brainstem centers,
      thalamus, and cerebellum 1 year after the accident. CONCLUSION: We demonstrate
      adaptive gray matter changes of pain processing structures in patients with
      chronic posttraumatic headache in regard to neuronal plasticity, thus providing a
      biologically plausible basis for this common, disabling problem.

PMID- 19770475
TI  - The present efficacy of multiple sclerosis therapeutics: Is the new 66% just the
      old 33%?
AB  - A challenge for the clinician treating patients with multiple sclerosis (MS) is
      to determine the most effective treatment while weighing the benefits and risks.
      Results of the phase 2 and phase 3 studies on natalizumab were received with
      great interest, in part due to the "improved" risk reduction for relapse rate,
      disease progression, and MRI metrics observed in comparison to results in trials
      of beta-interferon and glatiramer acetate. However, comparison across trials is
      invalid, in large part due to differences in the study populations. The increased
      efficacy observed in more recent trials has also been attributed to a fundamental
      change in subjects with MS enrolled in recent trials compared with the prior
      decade. In this article, we debate the relative efficacy of natalizumab vs the
      older injectable therapies.

PMID- 19770476
TI  - Severe cardiac failure in a patient with multiple sclerosis following low-dose
      mitoxantrone treatment.

PMID- 19770477
TI  - A patient with episodic ataxia and paramyotonia congenita due to mutations in
      KCNA1 and SCN4A.

PMID- 19770478
TI  - Weak hands from a flexed neck.

PMID- 19770479
TI  - Predictors of poor neurologic outcome after induced mild hypothermia following
      cardiac arrest.

PMID- 19770480
TI  - Autism spectrum disorders following in utero exposure to antiepileptic drugs.

PMID- 19770481
TI  - Education research: assessment of neurology resident clinical competencies in the
      neurology clinic.

PMID- 19770483
TI  - Toxicogenomics applied to cultures of human hepatocytes enabled an identification
      of novel petasites hybridus extracts for the treatment of migraine with improved
      hepatobiliary safety.
AB  - Butterbur extracts (Petasites hybridus) are recommended for the prevention of
      migraine, but pharmacovigilance reports may be suggestive of rare hepatobiliary
      toxicity. To evaluate its hepatotoxic potential, a series of in vivo and in vitro
      studies were carried out. Essentially, there were no signs of hepatocellular
      toxicity at estimated therapeutic C(max) levels of 60 ng/ml. Nonetheless, in a 28
      day toxicity study at approximately 200-fold of therapeutic doses, induced liver
      transaminases and bilirubin elevations were observed. In a subsequent 6-month
      chronic toxicity study, the initial hepatobiliary effects were reproduced, but at
      the end of the study, liver function recovered and returned to normal as
      evidenced by clinical chemistry measurements. To identify possible mechanisms of
      hepatotoxicity, we investigated liver function in vitro at > 170-fold of
      therapeutic C(max) levels, including cytotoxicity (lactate dehydrogenase, MTT,
      and ATP), transaminase activities (alanine aminotransferase and aspartate
      aminotransferase), albumin synthesis, urea and testosterone metabolism to assay
      for cytochrome P450 monooxygenase activity. Only with extracts rich in petasin
      (37% petasin) and at high and well above therapeutic doses, liver toxicity was
      observed. A toxicogenomic approach applied to hepatocyte cultures enabled
      hypothesis generation and was highly suggestive for extracts high in petasin
      content to impair bile acid transport and lipid and protein metabolism.
      Importantly, neither chronic rat in vivo nor rat in vitro studies predicted
      reliably hepatotoxicity, therefore reemphasizing the utility of human-based in
      vitro investigations for the development of safe medicinal products. Finally,
      toxicogenomics enabled the characterization of a novel butterbur extract with no
      signals for hepatotoxicity.

PMID- 19770484
TI  - Modulation of aflatoxin B1-mediated genotoxicity in primary cultures of human
      hepatocytes by diindolylmethane, curcumin, and xanthohumols.
AB  - This study employed cultured human primary hepatocytes to investigate the ability
      of the putative chemopreventive phytochemicals curcumin (CUR), 3,3'
      diindolylmethane (DIM), isoxanthohumol (IXN), or 8-prenylnaringenin (8PN) to
      reduce DNA adduct formation of the hepatocarcinogen aflatoxin B1 (AFB). Following
      48 h of pretreatment, DIM and 8PN significantly increased AFB-DNA adduct levels,
      whereas CUR and IXN had no effect. DIM greatly enhanced the transcriptional
      expression of cytochrome P450 (CYP) 1A1 and CYP1A2 mRNA. Glutathione S
      transferase mRNAs were not increased by any of the treatments. In vitro enzyme
      activity assays demonstrated that 8PN and DIM, but not CUR or IXN, inhibited
      human CYP1A1, CYP1A2, and CYP3A4 activities. To distinguish between treatment
      effects on transcription versus direct effects on enzyme activity for DIM, we
      evaluated the effects of pretreatment alone (transcriptional activation) versus
      cotreatment alone (enzyme inhibition). The results demonstrated that effects on
      gene expression, but not catalytic activity, are responsible for the observed
      effects of DIM on AFB-DNA adduct formation. The increase in AFB-DNA damage
      following DIM treatment may be explained through its substantial induction of
      CYP1A2 and/or its downregulation of GSTM1, both of which were significant. The
      increase in DNA damage by DIM raises potential safety risks for dietary
      supplements of DIM and its precursor indole-3-carbinol.

PMID- 19770485
TI  - S-Adenosylhomocysteine promotes the invasion of C6 glioma cells via increased
      secretion of matrix metalloproteinase-2 in murine microglial BV2 cells.
AB  - S-Adenosylhomocysteine (SAH) is a risk factor for many diseases, including tumor
      progression and neurodegenerative disease. In this study, we examined the
      hypothesis that SAH may indirectly enhance the invasion of C6 glioma cells by
      induction of matrix metalloproteinase-2 (MMP-2) secreted from the murine
      microglia BV2 cells. We obtained conditioned medium (CM) by incubating BV2 cells
      with SAH (1-50nM) for 24 h. We found that the SAH-containing CM (SAH-BV2-CM)
      strongly enhanced the invasiveness of C6 glioma cells and that this effect
      increased with increasing concentrations of SAH in the SAH-BV2-CM. The effect of
      CM could be attributed to its MMP-2 activity, as a result of increased protein
      and messenger RNA expression of MMP-2 in BV2 cells induced by SAH. In BV2 cells
      treated with SAH, the binding abilities of nuclear factor-kappa B (NF-kappaB) and
      stimulatory protein-1 (Sp1) to the MMP-2 promoter were increased, whereas the
      level of NF-kappaB inhibitor was decreased. In addition, SAH significantly
      increased the phosphorylation of extracellular signal-regulated kinase (ERK) and
      phosphatidylinositol-3-kinase/serine/threonine protein kinase (or protein kinase
      B) (PI3K/Akt) proteins but did not affect that of c-Jun NH2-terminal kinase or
      p38. Pretreatment of BV2 cells with an inhibitor specific for ERK (U0126)
      markedly abated the expression of ERK and MMP-2. Furthermore, SAH significantly
      and dose dependently decreased tissue inhibitor of metalloproteinase-2 (TIMP-2)
      in BV2 cells. Thus, SAH may induce the invasiveness of C6 glioma cells by
      decreased TIMP-2 expression and increased MMP-2 expression in BV2 cells. The
      latter effect is likely mediated through the ERK and PI3K/Akt pathways, with
      increased binding activities of NF-kappaB and Sp1 to the MMP-2 gene promoter.

PMID- 19770482
TI  - Approaches for assessing risks to sensitive populations: lessons learned from
      evaluating risks in the pediatric population.
AB  - Assessing the risk profiles of potentially sensitive populations requires a "tool
      chest" of methodological approaches to adequately characterize and evaluate these
      populations. At present, there is an extensive body of literature on
      methodologies that apply to the evaluation of the pediatric population. The
      Health and Environmental Sciences Institute Subcommittee on Risk Assessment of
      Sensitive Populations evaluated key references in the area of pediatric risk to
      identify a spectrum of methodological approaches. These approaches are considered
      in this article for their potential to be extrapolated for the identification and
      assessment of other sensitive populations. Recommendations as to future research
      needs and/or alternate methodological considerations are also made.

PMID- 19770486
TI  - Discrimination for genotoxic and nongenotoxic carcinogens by gene expression
      profiling in primary mouse hepatocytes improves with exposure time.
AB  - Assessing the potential carcinogenicity of chemicals for humans represents an
      ongoing challenge. Chronic rodent bioassays predict human cancer risk at only
      limited reliability and are simultaneously expensive and long lasting. In order
      to seek for alternatives, the ability of a transcriptomics-based primary mouse
      hepatocyte model to classify carcinogens by their modes of action was evaluated.
      As it is obvious that exposure will induce a cascade of gene expression
      modifications, in particular, the influence of exposure time in vitro on
      discriminating genotoxic (GTX) carcinogens from nongenotoxic (NGTX) carcinogens
      class discrimination was investigated. Primary mouse hepatocytes from male C57Bl6
      mice were treated for 12, 24, 36, and 48 h with two GTX and two NGTX carcinogens.
      For validation, two additional GTX compounds were studied at 24 and 48 h.
      Immunostaining of gammaH2AX foci was applied in order to phenotypically verify
      DNA damage. It confirmed significant induction of DNA damage after treatment with
      GTX compounds but not with NGTX compounds. Whole-genome gene expression
      modifications were analyzed by means of Affymetrix microarrays. When using
      differentially expressed genes from data sets normalized by Robust Multi-array
      Average, the two classes and various compounds were better separated from each
      other by hierarchical clustering when increasing the treatment period.
      Discrimination of GTX and NGTX carcinogens by Prediction Analysis of Microarray
      improved with time and resulted in correct classification of the validation
      compounds. The present study shows that gene expression profiling in primary
      mouse hepatocytes is promising for discriminating GTX from NGTX compounds and
      that this discrimination improves with increasing treatment period.

PMID- 19770487
TI  - Probucol increases glutathione peroxidase-1 activity and displays long-lasting
      protection against methylmercury toxicity in cerebellar granule cells.
AB  - Methylmercury (MeHg) is an environmental neurotoxicant whose molecular mechanisms
      underlying toxicity remain elusive. Here, we investigated molecular events
      involved in MeHg-induced neurotoxicity in cultured cerebellar granule cells
      (CGCs) as well as potential protective strategies for such toxicity. Glutathione
      peroxidase, isozyme 1 (GPx-1) activity was significantly (p = 0.0017) decreased
      at 24 h before MeHg-induced neuronal death (day in vitro 4). This event was
      related to enhanced susceptibilities to hydrogen peroxide or tert-butyl peroxide
      and increased lipid peroxidation. However, intracellular calcium levels,
      glutamate uptake, and glutathione levels, as well as glutathione reductase and
      catalase activities, were not changed by MeHg exposure at this time point.
      Probucol (PB), a lipid-lowering drug, displayed a long-lasting protective effect
      against MeHg-induced neurotoxicity. The beneficial effects of PB were correlated
      with increased GPx-1 activity and decreased lipid peroxidation. The protection
      afforded by PB was significantly higher when compared to the antioxidants,
      ascorbic acid and trolox. In vitro studies with the purified GPx-1 proved that
      MeHg inhibits and PB activates the enzyme activity. Overexpression of GPx-1
      prevented MeHg-induced neuronal death. These data indicate that (1) GPx-1 is an
      important molecular target involved in MeHg-induced neurotoxicity and (2) PB,
      which increases GPx-1 activity in CGCs, induces enduring protection against such
      toxicity. The results bring out new insights on the potential therapeutic
      strategies for poisonings to MeHg and other pathological conditions related to
      increased production and/or decreased detoxification of peroxides.

PMID- 19770488
TI  - Do the correlates of smoking cessation counseling differ across health
      professional groups?
AB  - INTRODUCTION: Smoking cessation counseling by health professionals is an
      effective approach to increase cessation rates among smokers. To guide the
      development of training and educational interventions, we surveyed six health
      professional groups including general practitioners (GPs), pharmacists, dentists,
      dental hygienists, nurses, and respiratory therapists, in order to describe
      current practices and identify the correlates of smoking cessation counseling.
      METHODS: Self-administered questionnaires were mailed to 500 persons randomly
      selected from the membership lists of active licensed professionals in each
      health professional group in Quebec. RESULTS: Response proportions ranged from
      52% (nurses) to 70% (dental hygienists). Compared with other groups, GPs and
      pharmacists undertook more counseling with patients ready to quit. GPs and
      respiratory therapists undertook more counseling with patients not ready to quit.
      Three factors emerged consistently across most groups as positively associated
      with counseling, including the belief that counseling is the role of health
      professionals, perceived self-efficacy to engage in effective counseling, and
      knowledge of community cessation resources. DISCUSSION: The correlates of
      cessation counseling are similar across health professional groups. Interventions
      that address beliefs that cessation counseling is the role of health
      professionals, self-efficacy to provide effective counseling, and knowledge of
      community resources may result in improved cessation counseling practices among
      health professionals.

PMID- 19770489
TI  - Background literature for publication.

PMID- 19770490
TI  - Adherence to National Asthma Education and Prevention Program's "How Asthma
      Friendly Is Your School?" recommendations.
AB  - School health policies and programs provide the framework for a safe and
      supportive environment for students with asthma. School Health Policies and
      Programs Study 2006 data were examined to assess whether schools nationwide have
      policies and programs consistent with the "How Asthma-Friendly Is Your School?"
      checklist from the National Asthma Education and Prevention Program. Adherence to
      some of the recommendations on the checklist was high. For example, 80% or more
      of schools allowed students to carry and self-administer asthma medications, and
      obtained and kept asthma action plans. For other recommendations, however, far
      fewer schools had the recommended polices or programs; most notably, less than
      one third of schools had a full-time Registered Nurse. Improvements in many
      school policies and programs are needed so that students have a safe and
      supportive school environment to help them control their asthma while away from
      home.

PMID- 19770492
TI  - Investigation and management of a child who is immunocompromised and neutropoenic
      with pulmonary infiltrates.

PMID- 19770491
TI  - Global white matter abnormalities in schizophrenia: a multisite diffusion tensor
      imaging study.
AB  - BACKGROUND: Emerging evidence implicates white matter (WM) abnormalities in the
      pathophysiology of schizophrenia. However, there is considerable heterogeneity in
      the presentation of WM abnormalities in the existing studies. The object of this
      study was to evaluate WM integrity in a large sample of patients with first
      episode (FE) and chronic schizophrenia in comparison to matched control groups.
      Our goal was to assess whether WM findings occurred early in the illness or
      whether these abnormalities developed with the illness over time. METHODS:
      Participants included 114 patients with schizophrenia (31 FE and 83 chronic
      patients) and 138 matched controls. High-resolution structural and diffusion
      tensor images were obtained on all participants. Measures of fractional
      anisotropy (FA) were calculated for the 4 cortical lobes and the cerebellum and
      brain stem. RESULTS: FA was significant lower in patients vs controls in the
      whole brain and individually in the frontal, parietal, occipital, and temporal
      lobes. FA was not significantly different in the brain stem or cerebellum. FA
      differences were significant only in patients with chronic schizophrenia and not
      in the FE group. CONCLUSIONS: We found global differences in the WM
      microstructure in patients with chronic but not FE schizophrenia. These findings
      suggest progressive alterations in WM microstructure.

PMID- 19770493
TI  - Investigating chronic meningitis.
AB  - Chronic meningitis is a syndrome characterised by persistent and progressive
      signs and symptoms of meningitis along with cerebrospinal fluid (CSF) pleocytosis
      and elevated protein that fail to improve over 4 weeks. A detailed and careful
      history and examination is required along with CSF parameters to guide a
      clinician towards the aetiology of the problem. Neuroimaging modalities have
      become a useful tool in the quest for a diagnosis in such cases. An interesting
      case is described in real time illustrating the process of making a diagnosis in
      chronic meningitis with an insight into investigations and subsequent management.

PMID- 19770494
TI  - New advances in the management of juvenile idiopathic arthritis--1: non
      biological therapy.
AB  - Juvenile idiopathic arthritis (JIA) is the most common paediatric rheumatic
      disease with significant long-term morbidity and mortality. Major advances have
      taken place in recent years in our understanding and the evidence base of JIA.
      Key to this has been the serious collaborative efforts of clinicians, academics,
      scientists and the whole of the multidisciplinary team. This has led to the
      important recognition and development of specialised expertise for the management
      of patients, improvement in global outcome measures and aggressive treatment of
      the significant complications of JIA. Important steps have taken place in
      optimising treatment of JIA. Clinical trials demonstrate that early use of intra
      articular corticosteroid injections alone or in addition to other systemic
      treatments can have a long-lasting effect. Robust evidence has defined the
      importance of methotrexate as the first-line disease modifying anti-rheumatic
      drug in JIA. Newer treatment options in severe refractory disease are now
      available including stem cell transplantation. This review focuses on the recent
      advances in non-biological therapies for treating JIA.

PMID- 19770495
TI  - New advances in the management of juvenile idiopathic arthritis--2: the era of
      biologicals.
AB  - Juvenile idiopathic arthritis (JIA) is the most common paediatric rheumatic
      disease with significant long-term morbidity and mortality. Major advances have
      taken place in recent years in our understanding and the evidence base of JIA.
      The advent of biological therapies has opened a major new era in the medical
      management of JIA with recent trials published of etanercept, infliximab,
      adalimumab, abatacept, tocilizumab and anakinra. National and international
      collaborative clinical and research networks are ideally placed to enable future
      advances in the management of JIA and all paediatric rheumatic disorders. This
      review follows on from Part 1 of a review of recent advances in non-biological
      therapies in JIA, and focuses on the significant new advances in biological
      therapies in managing JIA.

PMID- 19770496
TI  - Minding the gap: training in adolescent medicine when formal training programmes
      are not available.
AB  - There is a growing need for healthcare professionals to extend their knowledge in
      adolescent health care. Formal training curricula in adolescent medicine have
      been developed in only the United States, Canada and Australia. The Israeli
      experience in building an infrastructure that allows physicians to train in
      adolescent medicine is described. It includes the development of hospital-based
      and community-based multidisciplinary adolescent health services, a 3-year
      diploma course in adolescent medicine and a simulated patient-based programme
      regarding communication with adolescents. In the course of one decade an
      infrastructure has been developed to create a cadre of physicians who are able to
      operate adolescent clinics and to teach adolescent medicine. Consequently a
      formal fellowship training programme in adolescent medicine has been recently
      approved by the Scientific Council of the Israel Medical Association. This model
      can be applied in countries where formal training programmes in adolescent health
      care are not yet available.

PMID- 19770497
TI  - The role of IGF-1 and ghrelin in the compensation of intrauterine growth
      restriction.
AB  - The role of insulin-like growth factor 1 (IGF-1) and ghrelin in intrauterine
      growth restricted (IUGR) neonates in comparison to appropriate for gestational
      age (AGA) ones was investigated. Levels of IGF-1/insulin-like growth factor
      binding protein 3 (IGFBP3), ghrelin, insulin, and cortisol were determined in 20
      singleton, full-term IUGR and 20 respective AGA neonates at birth (umbilical cord
      UC), on days 1 (d1) and 4 (d4) postnatally. The ratio of IGF-1 to birth weight
      was higher in IUGR than in AGA in both UC (18.2 +/- 1.2 vs14.4 +/- 0.9, P = .05)
      and d1 (9.6 +/- 0.5 vs 6.8 +/- 0.3, P = .05). A significant positive correlation
      was found between IGF-1 and ghrelin levels and a negative one between IGFBP3 and
      ghrelin only in IUGR. In both groups, fetal IGF-1 levels negatively correlated
      with fetal cortisol levels. Intrauterine growth restricted neonates demonstrate a
      relative IGF-1 resistance in an attempt to drive energy toward survival on the
      expense of growth. The observed correlations between ghrelin and IGF-1/IGFBP3
      postnatally indicate that ghrelin might play a role in the compensation of
      intrauterine undernutrition, promoting postnatal growth.

PMID- 19770498
TI  - Overproduction, purification and structure determination of human dual
      specificity phosphatase 14.
AB  - Dual-specificity phosphatases (DUSPs) are enzymes that participate in the
      regulation of biological processes such as cell growth, differentiation,
      transcription and metabolism. A number of DUSPs are able to dephosphorylate
      phosphorylated serine, threonine and tyrosine residues on mitogen-activated
      protein kinases (MAPKs) and thus are also classified as MAPK phosphatases (MKPs).
      As an increasing number of DUSPs are being identified and characterized, there is
      a growing need to understand their biological activities at the molecular level.
      There is also significant interest in identifying DUSPs that could be potential
      targets for drugs that modulate MAPK-dependent signaling and immune responses,
      which have been implicated in a variety of maladies including cancer, infectious
      diseases and inflammatory disorders. Here, the overproduction, purification and
      crystal structure at 1.88 A resolution of human dual-specificity phosphatase 14,
      DUSP14 (MKP6), are reported. This structural information should accelerate the
      study of DUSP14 at the molecular level and may also accelerate the discovery and
      development of novel therapeutic agents.

PMID- 19770499
TI  - Structure of the two-domain hexameric APS kinase from Thiobacillus denitrificans:
      structural basis for the absence of ATP sulfurylase activity.
AB  - The Tbd_0210 gene of the chemolithotrophic bacterium Thiobacillus denitrificans
      is annotated to encode a 60.5 kDa bifunctional enzyme with ATP sulfurylase and
      APS kinase activity. This putative bifunctional enzyme was cloned, expressed and
      structurally characterized. The 2.95 A resolution X-ray crystal structure
      reported here revealed a hexameric assembly with D(3) symmetry. Each subunit
      contains a large N-terminal sulfurylase-like domain and a C-terminal APS kinase
      domain reminiscent of the two-domain fungal ATP sulfurylases of Penicillium
      chrysogenum and Saccharomyces cerevisiae, which also exhibit a hexameric
      assembly. However, the T. denitrificans enzyme exhibits numerous structural and
      sequence differences in the N-terminal domain that render it inactive with
      respect to ATP sulfurylase activity. Surprisingly, the C-terminal domain does
      indeed display APS kinase activity, indicating that this gene product is a true
      APS kinase. Therefore, these results provide the first structural insights into a
      unique hexameric APS kinase that contains a nonfunctional ATP sulfurylase-like
      domain of unknown function.

PMID- 19770500
TI  - End-to-end and end-to-middle interhelical interactions: new classes of
      interacting helix pairs in protein structures.
AB  - Helix-helix interactions are important for the structure, stability and function
      of alpha-helical proteins. Helices that either cross in the middle or show
      extensive contacts between each other, such as coiled coils, have been
      investigated in previous studies. Interactions between two helices can also occur
      only at the terminal regions or between the terminal region of one helix and the
      middle region of another helix. Examples of such helix pairs are found in
      aquaporin, H(+)/Cl(-) transporter and Bcl-2 proteins. The frequency of the
      occurrence of such ;end-to-end' (EE) and ;end-to-middle' (EM) helix pairs in
      protein structures is not known. Questions regarding the residue preferences in
      the interface and the mode of interhelical interactions in such helix pairs also
      remain unanswered. In this study, high-resolution structures of all-alpha
      proteins from the PDB have been systematically analyzed and the helix pairs that
      interact only in EE or EM fashion have been extracted. EE and EM helix pairs have
      been categorized into five classes (N-N, N-C, C-C, N-MID and C-MID) depending on
      the region of interaction. Nearly 13% of 5725 helix pairs belonged to one of the
      five classes. Analysis of single-residue propensities indicated that hydrophobic
      and polar residues prefer to occur in the C-terminal and N-terminal regions,
      respectively. Hydrophobic C-terminal interacting residues and polar N-terminal
      interacting residues are also highly conserved. A strong correlation exists
      between some of the residue properties (surface area/volume and length of side
      chains) and their preferences for occurring in the interface of EE and EM helix
      pairs. In contrast to interacting non-EE/EM helix pairs, helices in EE and EM
      pairs are farther apart. In these helix pairs, residues with large surface
      area/volume and longer side chains are preferred in the interfacial region.

PMID- 19770501
TI  - A neutron crystallographic analysis of T6 porcine insulin at 2.1 A resolution.
AB  - Neutron diffraction data for T(6) porcine insulin were collected to 2.1 A
      resolution from a single crystal partly deuterated by exchange of mother liquor.
      A maximum-likelihood structure refinement was undertaken using the neutron data
      and the structure was refined to a residual of 0.179. The hydrogen-bonding
      network of the central core of the hexamer was observed and the charge balance
      between positively charged Zn ions and their surrounding structure was
      interpreted by considering the protonation and/or deprotonation states and
      interactions of HisB10, water and GluB13. The observed double conformation of
      GluB13 was essential to interpreting the charge balance and could be compared
      with the structure of a dried crystal of T(6) human insulin at 100 K. Differences
      in the dynamic behaviour of the water molecules coordinating the upper and lower
      Zn ions were observed and interpreted. The hydrogen bonds in the insulin
      molecules, as well as those involving HisB10 and GluB13, are discussed. The
      hydrogen/deuterium (H/D) exchange ratios of the amide H atoms of T(6) porcine
      insulin in crystals were obtained and showed that regions highly protected from
      H/D exchange are concentrated in the centre of a helical region of the B chains.
      From the viewpoint of soaking time versus H/D-exchange ratios, the amide H atoms
      can be classified into three categories.

PMID- 19770502
TI  - A multivariate likelihood SIRAS function for phasing and model refinement.
AB  - A likelihood function based on the multivariate probability distribution of all
      observed structure-factor amplitudes from a single isomorphous replacement with
      anomalous scattering experiment has been derived and implemented for use in
      substructure refinement and phasing as well as macromolecular model refinement.
      Efficient calculation of a multidimensional integration required for function
      evaluation has been achieved by approximations based on the function's
      properties. The use of the function in both phasing and protein model building
      with iterative refinement was essential for successful automated model building
      in the test cases presented.

PMID- 19770504
TI  - electronic Ligand Builder and Optimization Workbench (eLBOW): a tool for ligand
      coordinate and restraint generation.
AB  - The electronic Ligand Builder and Optimization Workbench (eLBOW) is a program
      module of the PHENIX suite of computational crystallographic software. It is
      designed to be a flexible procedure that uses simple and fast quantum-chemical
      techniques to provide chemically accurate information for novel and known ligands
      alike. A variety of input formats and options allow the attainment of a number of
      diverse goals including geometry optimization and generation of restraints.

PMID- 19770503
TI  - Effects of impurities on membrane-protein crystallization in different systems.
AB  - When starting a protein-crystallization project, scientists are faced with
      several unknowns. Amongst them are these questions: (i) is the purity of the
      starting material sufficient? and (ii) which type of crystallization experiment
      is the most promising to conduct? The difficulty in purifying active membrane
      protein samples for crystallization trials and the high costs associated with
      producing such samples require an extremely pragmatic approach. Additionally,
      practical guidelines are needed to increase the efficiency of membrane-protein
      crystallization. In order to address these conundrums, the effects of commonly
      encountered impurities on various membrane-protein crystallization regimes have
      been investigated and it was found that the lipidic cubic phase (LCP) based
      crystallization methodology is more robust than crystallization in detergent
      environments using vapor diffusion or microbatch approaches in its ability to
      tolerate contamination in the forms of protein, lipid or other general membrane
      components. LCP-based crystallizations produced crystals of the photosynthetic
      reaction center (RC) of Rhodobacter sphaeroides from samples with substantial
      levels of residual impurities. Crystals were obtained with protein contamination
      levels of up to 50% and the addition of lipid material and membrane fragments to
      pure samples of RC had little effect on the number or on the quality of crystals
      obtained in LCP-based crystallization screens. If generally applicable, this
      tolerance for impurities may avoid the need for samples of ultrahigh purity when
      undertaking initial crystallization screening trials to determine preliminary
      crystallization conditions that can be optimized for a given target protein.

PMID- 19770505
TI  - Structural insights into the adaptation of proliferating cell nuclear antigen
      (PCNA) from Haloferax volcanii to a high-salt environment.
AB  - The sliding clamp proliferating cell nuclear antigen (PCNA) plays vital roles in
      many aspects of DNA replication and repair in eukaryotic cells and in archaea.
      Realising the full potential of archaea as a model for PCNA function requires a
      combination of biochemical and genetic approaches. In order to provide a platform
      for subsequent reverse genetic analysis, PCNA from the halophilic archaeon
      Haloferax volcanii was subjected to crystallographic analysis. The gene was
      cloned and expressed in Escherichia coli and the protein was purified by affinity
      chromatography and crystallized by the vapour-diffusion technique. The structure
      was determined by molecular replacement and refined at 3.5 A resolution to a
      final R factor of 23.7% (R(free) = 25%). PCNA from H. volcanii was found to be
      homotrimeric and to resemble other homotrimeric PCNA clamps but with several
      differences that appear to be associated with adaptation of the protein to the
      high intracellular salt concentrations found in H. volcanii cells.

PMID- 19770506
TI  - On the combination of molecular replacement and single-wavelength anomalous
      diffraction phasing for automated structure determination.
AB  - A combination of molecular replacement and single-wavelength anomalous
      diffraction phasing has been incorporated into the automated structure
      determination platform Auto-Rickshaw. The complete MRSAD procedure includes
      molecular replacement, model refinement, experimental phasing, phase improvement
      and automated model building. The improvement over the standard SAD or MR
      approaches is illustrated by ten test cases taken from the JCSG diffraction data
      set database. Poor MR or SAD phases with phase errors larger than 70 degrees can
      be improved using the described procedure and a large fraction of the model can
      be determined in a purely automatic manner from X-ray data extending to better
      than 2.6 A resolution.

PMID- 19770507
TI  - Structure of D-alanine-D-alanine ligase from Thermus thermophilus HB8: cumulative
      conformational change and enzyme-ligand interactions.
AB  - D-Alanine-D-alanine ligase (Ddl) is one of the key enzymes in peptidoglycan
      biosynthesis and is an important target for drug discovery. The enzyme catalyzes
      the condensation of two D-Ala molecules using ATP to produce D-Ala-D-Ala, which
      is the terminal peptide of a peptidoglycan monomer. The structures of five forms
      of the enzyme from Thermus thermophilus HB8 (TtDdl) were determined: unliganded
      TtDdl (2.3 A resolution), TtDdl-adenylyl imidodiphosphate (2.6 A), TtDdl-ADP (2.2
      A), TtDdl-ADP-D-Ala (1.9 A) and TtDdl-ATP-D-Ala-D-Ala (2.3 A). The central domain
      rotates as a rigid body towards the active site in a cumulative manner in concert
      with the local conformational change of three flexible loops depending upon
      substrate or product binding, resulting in an overall structural change from the
      open to the closed form through semi-open and semi-closed forms. Reaction
      intermediate models were simulated using TtDdl-complex structures and other Ddl
      structures previously determined by X-ray methods. The catalytic process
      accompanied by the cumulative conformational change has been elucidated based on
      the intermediate models in order to provide new insights regarding the details of
      the catalytic mechanism.

PMID- 19770508
TI  - Modeling discrete heterogeneity in X-ray diffraction data by fitting multi
      conformers.
AB  - The native state of a protein is regarded to be an ensemble of conformers, which
      allows association with binding partners. While some of this structural
      heterogeneity is retained upon crystallization, reliably extracting heterogeneous
      features from diffraction data has remained a challenge. In this study, a new
      algorithm for the automatic modelling of discrete heterogeneity is presented. At
      high resolution, the authors' single multi-conformer model, with correlated
      structural features to represent heterogeneity, shows improved agreement with the
      diffraction data compared with a single-conformer model. The model appears to be
      representative of the set of structures present in the crystal. In contrast,
      below 2 A resolution representing ambiguous electron density by correlated multi
      conformers in a single model does not yield better agreement with the
      experimental data. Consistent with previous studies, this suggests that
      variability in multi-conformer models at lower resolution levels reflects
      uncertainty more than coordinated motion.

PMID- 19770509
TI  - A new crystal form of human tear lipocalin reveals high flexibility in the loop
      region and induced fit in the ligand cavity.
AB  - Tear lipocalin (TLC) with the bound artificial ligand 1,4-butanediol has been
      crystallized in space group P2(1) with four protein molecules in the asymmetric
      unit and its X-ray structure has been solved at 2.6 A resolution. TLC is a member
      of the lipocalin family that binds ligands with diverse chemical structures, such
      as fatty acids, phospholipids and cholesterol as well as microbial siderophores
      and the antibiotic rifampin. Previous X-ray structural analysis of apo TLC
      crystallized in space group C2 revealed a rather large bifurcated ligand pocket
      and a partially disordered loop region at the entrace to the cavity. Analysis of
      the P2(1) crystal form uncovered major conformational changes (i) in beta-strands
      B, C and D, (ii) in loops 1, 2 and 4 at the open end of the beta-barrel and (iii)
      in the extended C-terminal segment, which is attached to the beta-barrel via a
      disulfide bridge. The structural comparison indicates high conformational
      plasticity of the loop region as well as of deeper parts of the ligand pocket,
      thus allowing adaptation to ligands that differ vastly in size and shape. This
      illustrates a mechanism for promiscuity in ligand recognition which may also be
      relevant for some other physiologically important members of the lipocalin
      protein family.

PMID- 19770510
TI  - Resolving lung injury: a new role for Tregs in controlling the innate immune
      response.
AB  - Inflammation-associated lung injury is a major cause of morbidity and mortality
      for patients in intensive care units. Although the cellular and molecular events
      that initiate lung inflammation are now well understood, the mechanisms that
      promote its resolution remain poorly defined. In this issue of the JCI, D'Alessio
      et al. show in a mouse model that recovery from acute lung injury is not simply a
      passive process, but involves Tregs in an active resolution program (see the
      related article beginning on page 2898).

PMID- 19770511
TI  - Breast cancer gene variants: separating the harmful from the harmless.
AB  - Individuals carrying a mutation in the breast cancer 1, early onset gene (BRCA1)
      are at increased risk of breast or ovarian cancer and thus are candidates for
      risk reduction strategies such as oophorectomy and mastectomy. A recurring
      problem in the clinic is that many detectable changes within the BRCA1 gene
      produce subtle alterations to the protein that are not easily recognized as
      either harmful (loss-of-function) alleles or harmless and thus inconsequential
      polymorphisms. In this issue of the JCI, Chang, Sharan, and colleagues describe a
      novel system to evaluate human BRCA1 alleles for in vivo function using BACs
      containing human BRCA1 vectors in mouse cells and embryos (see the related
      article beginning on page 3160). This strategy should provide new avenues for
      clinicians to interpret results of genetic testing of BRCA1 variants and for
      researchers to study the basic molecular mechanisms of BRCA1 function in in vivo
      model systems.

PMID- 19770512
TI  - Reduced thymus activity and infection prematurely age the immune system.
AB  - The aging process affects all aspects of the immune system, particularly the T
      cells. The immune system in older individuals is often characterized by lower T
      cell numbers, lower naive/memory T cell ratios, and lower T cell diversity. Most
      measures of inflammation increase with age. Why this happens, and why there is so
      much person-to-person variability in these changes, is not known. In this issue
      of the JCI, Sauce and colleagues show that removal of the thymus during infancy
      results in premature onset of many of these age-associated changes to the immune
      system (see the related article beginning on page 3070). The effect of thymectomy
      was particularly notable in those individuals who acquired CMV infection. Data
      from this study, as well as data from other observational settings, suggest that
      reduced thymic function and persistent viral infections combine to accelerate a
      decline in immunologic function.

PMID- 19770513
TI  - B cells produce pathogenic antibodies and impair recovery after spinal cord
      injury in mice.
AB  - Traumatic injury to the mammalian spinal cord activates B cells, which culminates
      in the synthesis of autoantibodies. The functional significance of this immune
      response is unclear. Here, we show that locomotor recovery was improved and
      lesion pathology was reduced after spinal cord injury (SCI) in mice lacking B
      cells. After SCI, antibody-secreting B cells and Igs were present in the
      cerebrospinal fluid and/or injured spinal cord of WT mice but not mice lacking B
      cells. In mice with normal B cell function, large deposits of antibody and
      complement component 1q (C1q) accumulated at sites of axon pathology and
      demyelination. Antibodies produced after SCI caused pathology, in part by
      activating intraspinal complement and cells bearing Fc receptors. These data
      indicate that B cells, through the production of antibodies, affect pathology in
      SCI. One or more components of this pathologic immune response could be
      considered as novel therapeutic targets for minimizing tissue injury and/or
      promoting repair after SCI.

PMID- 19770514
TI  - Evidence of premature immune aging in patients thymectomized during early
      childhood.
AB  - While the thymus is known to be essential for the initial production of T cells
      during early life, its contribution to immune development remains a matter of
      debate. In fact, during cardiac surgery in newborns, the thymus is completely
      resected to enable better access to the heart to correct congenital heart
      defects, suggesting that it may be dispensable during childhood and adulthood.
      Here, we show that young adults thymectomized during early childhood exhibit an
      altered T cell compartment. Specifically, absolute CD4+ and CD8+ T cell counts
      were decreased, and these T cell populations showed substantial loss of naive
      cells and accumulation of oligoclonal memory cells. A subgroup of these young
      patients (22 years old) exhibited a particularly altered T cell profile that is
      usually seen in elderly individuals (more than 75 years old). This condition was
      directly related to CMV infection and the induction of strong CMV-specific T cell
      responses, which may exhaust the naive T cell pool in the absence of adequate T
      cell renewal from the thymus. Together, these marked immunological alterations
      are reminiscent of the immune risk phenotype, which is defined by a cluster of
      immune markers predictive of increased mortality in the elderly. Overall, our
      data highlight the importance of the thymus in maintaining the integrity of T
      cell immunity during adult life.

PMID- 19770515
TI  - NF-kappaB p100 limits TNF-induced bone resorption in mice by a TRAF3-dependent
      mechanism.
AB  - TNF and RANKL mediate bone destruction in common bone diseases, including
      osteoarthritis and RA. They activate NF-kappaB canonical signaling directly in
      osteoclast precursors (OCPs) to induce osteoclast formation in vitro. However,
      unlike RANKL, TNF does not activate the alternative NF-kappaB pathway efficiently
      to process the IkappaB protein NF-kappaB p100 to NF-kappaB p52, nor does it
      appear to induce osteoclast formation in vivo in the absence of RANKL. Here, we
      show that TNF limits RANKL- and TNF-induced osteoclast formation in vitro and in
      vivo by increasing NF-kappaB p100 protein accumulation in OCPs. In contrast, TNF
      induced robust osteoclast formation in vivo in mice lacking RANKL or RANK when
      the mice also lacked NF-kappaB p100, and TNF-Tg mice lacking NF-kappaB p100 had
      more severe joint erosion and inflammation than did TNF-Tg littermates. TNF, but
      not RANKL, increased OCP expression of TNF receptor-associated factor 3 (TRAF3),
      an adapter protein that regulates NF-kappaB p100 levels in B cells. TRAF3 siRNA
      prevented TNF-induced NF-kappaB p100 accumulation and inhibition of
      osteoclastogenesis. These findings suggest that upregulation of TRAF3 or NF
      kappaB p100 expression or inhibition of NF-kappaB p100 degradation in OCPs could
      limit bone destruction and inflammation-induced bone loss in common bone
      diseases.

PMID- 19770516
TI  - The peptidyl-prolyl isomerase Pin1 determines parathyroid hormone mRNA levels and
      stability in rat models of secondary hyperparathyroidism.
AB  - Secondary hyperparathyroidism is a major complication of chronic kidney disease
      (CKD). In experimental models of secondary hyperparathyroidism induced by
      hypocalcemia or CKD, parathyroid hormone (PTH) mRNA levels increase due to
      increased PTH mRNA stability. K-homology splicing regulator protein (KSRP)
      decreases the stability of PTH mRNA upon binding a cis-acting element in the PTH
      mRNA 3' UTR region. As the peptidyl-prolyl isomerase (PPIase) Pin1 has recently
      been shown to regulate the turnover of multiple cytokine mRNAs, we investigated
      the role of Pin1 in regulating PTH mRNA stability in rat parathyroids and
      transfected cells. The data generated were consistent with Pin1 being a PTH mRNA
      destabilizing protein. Initial analysis indicated that Pin1 activity was
      decreased in parathyroid protein extracts from both hypocalcemic and CKD rats and
      that pharmacologic inhibition of Pin1 increased PTH mRNA levels
      posttranscriptionally in rat parathyroid and in transfected cells. Pin1 mediated
      its effects via interaction with KSRP, which led to KSRP dephosphorylation and
      activation. In the rat parathyroid, Pin1 inhibition decreased KSRP-PTH mRNA
      interactions, increasing PTH mRNA levels. Furthermore, Pin1-/- mice displayed
      increased serum PTH and PTH mRNA levels, suggesting that Pin1 determines basal
      PTH expression in vivo. These results demonstrate that Pin1 is a key mediator of
      PTH mRNA stability and indicate a role for Pin1 in the pathogenesis of secondary
      hyperparathyroidism in individuals with CKD.

PMID- 19770517
TI  - Pathogenic antibodies are active participants in spinal cord injury.
AB  - The role of B cells and autoimmunity as contributing factors to poor neurological
      outcomes following spinal cord injury (SCI) is poorly understood. The study by
      Ankeny et al., in this issue of the JCI, identifies a new immunopathological
      mechanism arising after SCI in mice (see the related article beginning on page
      2990). The study shows that B cells produce pathogenic antibodies that impair
      lesion repair, resulting in worse neurological outcome. This new understanding of
      SCI disease pathogenesis, if confirmed in humans, reveals potential avenues for
      the development of novel neuroprotective immunotherapies.

PMID- 19770519
TI  - NF-kappaB2 (p100) limits TNF-alpha-induced osteoclastogenesis.
AB  - Bone undergoes a continuous cycle of renewal, and osteoclasts--the cells
      responsible for bone resorption--play a pivotal role in bone homeostasis. This
      resorption is largely mediated by inflammatory cytokines such as TNF-alpha. In
      this issue of the JCI, Yao et al. demonstrate that the NF-kappaB precursor
      protein NF-kappaB2 (p100) acts as a negative regulator of osteoclastogenesis (see
      the related article beginning on page 3024). TNF-alpha induced a sustained
      accumulation of p100 in osteoclast precursors, and TNF-alpha-induced osteoclast
      formation was markedly increased in Nfkb2-/- mice. They also found that TNF
      receptor-associated factor 3 (TRAF3) is involved in the posttranslational
      regulation of p100 expression. These results suggest that blockade of the
      processing of p100 is a novel strategy to treat TNF-alpha-related bone diseases
      such as RA.

PMID- 19770518
TI  - Pin1 regulates parathyroid hormone mRNA stability.
AB  - Secondary hyperparathyroidism often occurs in chronic kidney disease (CKD) and
      vitamin D deficiency, resulting in increased fractures and mortality.
      Understanding factors that stimulate parathyroid hormone (PTH) synthesis is
      important for devising methods to treat this condition. Previous work has
      demonstrated that murine Pth mRNA levels are regulated by proteins that bind AU
      rich elements (AREs) within the 3' UTR region of Pth mRNA and influence Pth mRNA
      stability. In this issue of the JCI, Nechama et al. demonstrate that in murine
      secondary hyperparathyroidism associated with CKD or Ca deficiency, the activity
      of Pin1, a peptidyl-prolyl isomerase, is reduced (see the related article
      beginning on page 3102). Reduced Pin1 activity resulted in the phosphorylation
      and degradation of an ARE-binding protein, K-homology splicing regulator protein
      (KSRP), which normally enhances the degradation of Pth mRNA. The activity of
      other ARE-binding proteins, such as AU-rich binding factor 1 (AUF1), that
      increase Pth mRNA stability, was increased, thereby increasing PTH synthesis.
      This work suggests new ways by which to regulate PTH synthesis in secondary
      hyperparathyroidism.

PMID- 19770520
TI  - Expression of human BRCA1 variants in mouse ES cells allows functional analysis
      of BRCA1 mutations.
AB  - To date, inheritance of a mutant BRCA1 or BRCA2 gene is the best-established
      indicator of an increased risk of developing breast cancer. Sequence analysis of
      these genes is being used to identify BRCA1/2 mutation carriers, though these
      efforts are hampered by the high frequency of variants of unknown clinical
      significance (VUSs). Functional evaluation of such variants has been restricted
      due to lack of a physiologically relevant assay. In this study we developed a
      functional assay using mouse ES cells to study variants of BRCA1. We introduced
      BAC clones with human wild-type BRCA1 or variants into Brca1-null ES cells and
      confirmed that only wild-type and a known neutral variant rescued cell lethality.
      The same neutral variant was also able to rescue embryogenesis in Brca1-null
      mice. A test of several BRCT domain mutants revealed all to be deleterious,
      including a VUS. Furthermore, we used this assay to determine the effects of
      BRCA1 variants on cell cycle regulation, differentiation, and genomic stability.
      Importantly, we discovered that ES cells rescued by S1497A BRCA1 exhibited
      significant hypersensitivity after gamma-irradiation. Our results demonstrate
      that this ES cell-based assay is a powerful and reliable method for analyzing the
      functional impact of BRCA1 variants, which we believe could be used to determine
      which patients may require preventative treatments.

PMID- 19770522
TI  - Natural disasters in developing countries: mental health issues.

PMID- 19770523
TI  - Risk of posttraumatic stress disorder and depression in survivors of the floods
      in Bihar, India.
AB  - BACKGROUND: Following a natural disaster, survivors are vulnerable to develop
      posttraumatic stress disorder (PTSD) and/ or depression. OBJECTIVES: (i) To
      screen survivors of the Bihar floods a month after the event to determine their
      scores in a screening questionnaire for PTSD and/ or depression and (ii) to
      correlate these scores with age and gender. MATERIALS AND METHODS: One thousand
      two hundred eighty-nine persons (645 females) who had been directly exposed to
      the floods in Bihar, India, in August 2008 were assessed. The Screening
      Questionnaire for Disaster Mental Health (SQD) was used to screen for PTSD and
      depression. STATISTICAL ANALYSIS: Separate two-factor ANOVAs were used to compare
      persons of both sexes and 5 different age groups for PTSD and depression scores.
      This was followed by post-hoc analysis for multiple comparisons. RESULTS: People
      over the age of 60 years had significantly higher scores for PTSD and depression
      compared to all groups (P< 0.05 for all comparisons). CONCLUSION: Following a
      natural disaster, older people appear more vulnerable to develop PTSD and
      depression. This should be taken into account in devising strategies for disaster
      relief.

PMID- 19770521
TI  - CD4+CD25+Foxp3+ Tregs resolve experimental lung injury in mice and are present in
      humans with acute lung injury.
AB  - Acute lung injury (ALI) is characterized by rapid alveolar injury, inflammation,
      cytokine induction, and neutrophil accumulation. Although early events in the
      pathogenesis of ALI have been defined, the mechanisms underlying resolution are
      unknown. As a model of ALI, we administered intratracheal (i.t.) LPS to mice and
      observed peak lung injury 4 days after the challenge, with resolution by day 10.
      Numbers of alveolar lymphocytes increased as injury resolved. To examine the role
      of lymphocytes in this response, lymphocyte-deficient Rag-1-/- and C57BL/6 WT
      mice were exposed to i.t. LPS. The extent of injury was similar between the
      groups of mice through day 4, but recovery was markedly impaired in the Rag-1-/-
      mice. Adoptive transfer studies revealed that infusion of CD4+CD25+Foxp3+ Tregs
      as late as 24 hours after i.t. LPS normalized resolution in Rag-1-/- mice.
      Similarly, Treg depletion in WT mice delayed recovery. Treg transfer into i.t.
      LPS-exposed Rag-1-/- mice also corrected the elevated levels of alveolar
      proinflammatory cytokines and increased the diminished levels of alveolar TGF
      beta and neutrophil apoptosis. Mechanistically, Treg-mediated resolution of lung
      injury was abrogated by TGF-beta inhibition. Moreover, BAL of patients with ALI
      revealed dynamic changes in CD3+CD4+CD25hiCD127loFoxp3+ cells. These results
      indicate that Tregs modify innate immune responses during resolution of lung
      injury and suggest potential targets for treating ALI, for which there are no
      specific therapies currently available.

PMID- 19770524
TI  - Paraoxonase 1 gene polymorphisms contribute to coronary artery disease risk among
      north Indians.
AB  - BACKGROUND: Polymorphisms in paraoxonase 1 (PON1) coding for PON1 enzyme have
      been studied as genetic markers of coronary artery disease (CAD). PON1 Q192R and
      PON1 L55M polymorphisms have been analyzed extensively, but data on association
      and role of these polymorphisms in the etiology of CAD are conflicting. In this
      study, we tested the genetic association between PON1 Q192R and PON1 L55M
      polymorphisms and CAD among north Indians. MATERIALS AND METHODS: Two hundred
      eighty-five angiographically proven patients with coronary artery disease and 200
      sex-matched and ethnically matched controls were genotyped for 2 PON1
      polymorphisms by the polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) technique. Genotype/ allele frequencies were compared in
      patients and controls using the chi-square test. RESULTS: At PON1-192 locus,
      there were significant differences between patients and controls (P< 0.05),
      leading to significant odds ratios for RR genotype (OR= 1.92, CI: 1.19-3.10) and
      *R allele (OR= 1.30, CI: 1.00-1.70). These odds ratios were higher in the sub
      sample of smokers (2.84 and 1.45, respectively). Binary logistic regression
      analysis also confirmed that *R allele carriers (QR and RR) have a higher risk of
      CAD (OR= 3.54, CI: 1.67-5.53). PON1-55 locus did not show significant differences
      between patients and controls, but LL genotype and *L allele were significant
      risk factors in the nonsmoker group. RL haplotype was also significantly
      associated with CAD risk (OR= 1.44, CI: 1.08-1.93). CONCLUSIONS: PON1-192R allele
      and RR genotype are significantly associated with CAD patients from the north
      Indian population (Uttar Pradesh). This association was stronger in smokers,
      supporting the conclusion that an interaction between PON1 activity and smoking
      augments CAD risk. Further studies with larger sample size are warranted to
      confirm these associations in different Indian populations.

PMID- 19770525
TI  - Acute childhood morbidities in rural Wardha: some epidemiological correlates and
      health care seeking.
AB  - BACKGROUND: In India, common morbidities among children under 3 years of age are
      fever, acute respiratory infections, diarrhea. Effective early management at the
      home level and health care-seeking behavior in case of appearance of danger signs
      are key strategies to prevent the occurrence of severe and life-threatening
      complications. OBJECTIVES: To find out the prevalence of acute child morbidities,
      their determinants and health-seeking behavior of the mothers of these children.
      SETTING AND DESIGN: The cross-sectional study was carried out in Wardha district
      of central India. MATERIAL AND METHODS: We interviewed 990 mothers of children
      below 3 years of age using 30-cluster sampling method. Nutritional status was
      defined by National Center for Health Statistics (NCHS) reference. Composite
      index of anthropometric failure (CIAF) was constructed. Hemoglobin concentration
      in each child was estimated using the 'filter paper cyanm ethemoglobin method.'
      Using World Health Organization guidelines, anemia was defined as hemoglobin
      concentration less than 110 g/L. Post-survey focus group discussions (FGDs) were
      undertaken to bridge gaps in information obtained from the survey. STATISTICAL
      ANALYSIS: The data was analyzed by using SPSS 12.0.1 software package. Chi-square
      was used to test the association, while odds ratios were calculated to measure
      the strength of association. Multiple logistic regression analysis was applied to
      derive the final model. RESULTS: Anemia was detected in 80.3% of children, and
      59.6% of children were undernourished as indicated by CIAF. The overall
      prevalence of acute morbidity was 59.9%. Children with mild anemia, moderate
      anemia and severe anemia had 1.52, 1.61 and 9.21 times higher risk of being
      morbid, respectively. Similarly, children with single, 2 and 3 anthropometric
      failures had 1.16, 1.29 and 2.27 times higher risk of being morbid, respectively.
      Out of 594 (60%) children with at least one of the acute morbidities, 520 (87.5%)
      sought health care, where majority (66.1%) received treatment from private
      clinics. The final model suggested that anemia and mother's poor educational
      status are predictors of childhood morbidity. CONCLUSIONS: Nutritional anemia and
      mother's poor educational status are the most important risk factors of acute
      childhood morbidity. There is need to revitalize existing health care delivery
      and child health programs in rural India with emphasis on immediate correction of
      nutritional anemia.

PMID- 19770526
TI  - Simultaneous isolated bilateral facial palsy: a rare vincristine-associated
      toxicity.
AB  - We describe a case of a 15-year-old boy with vincristine-induced simultaneous
      isolated bilateral facial palsy. The boy presented with superior vena caval
      syndrome (SVC syndrome), right-sided pleural effusion and anterior mediastinal
      lymphadenopathy. Histopathological examination of left axillary lymph node was
      suggestive of lymphoblastic lymphoma. We started chemotherapy with
      cyclophosphamide, doxorubicin, vincristine and prednisolone. SVC syndrome
      disappeared completely after the 1st cycle, and he achieved remission after the
      3rd cycle of chemotherapy. He noticed that he could not close his eyes.
      Neurological examination revealed bilateral lower motor neuron facial palsy.
      Findings from examination of other cranial nerves and peripheral nerves were
      normal. Results of MRI of brain and cerebrospinal fluid examination were normal.
      He received 6 mg vincristine before developing toxicity.

PMID- 19770527
TI  - Type 1 leprosy reversal reaction treated with topical tacrolimus along with
      systemic corticosteroids.
AB  - An 11-year-old black Haitian boy presented with borderline lepromatous leprosy
      and was treated with rifampicin, dapsone, and clofazimine. After 4 months he
      developed a severe type 1 reversal reaction without nerve involvement. He was
      started on prednisolone (1 mg/kg daily). After 4 weeks of treatment with
      corticosteroids, his condition did not improve and the lesions remained painful.
      The patient was given a therapeutic trial with twice daily application of topical
      tacrolimus 0.1% ointment. The result was a dramatic improvement in the skin
      lesions. The patient's condition was maintained by topical tacrolimus therapy,
      with healing of all skin lesions. The prednisolone dose was then tapered to zero
      over a period of 12 weeks. To the best of our knowledge, this is the first report
      of the efficacy of topical tacrolimus in the treatment of type 1 leprosy
      reaction.

PMID- 19770528
TI  - Asystole during dipyridamole administration.

PMID- 19770529
TI  - Hyoscine-B butyl bromide in labor: a randomized controlled trial.

PMID- 19770530
TI  - Aspergillus endophthalmitis: pars plana vitrectomy is an alternative.

PMID- 19770531
TI  - Leptospirosis in children: a review for family physicians.
AB  - Leptospirosis is an important cause of acute febrile illness in the monsoon
      season in India. It is a zoonotic disease that is spread primarily by rodents.
      There exist two clinical types: anicteric and icteric leptospirosis. Both have an
      initial septicemic phase followed by an immune phase. The clinical manifestations
      vary and the disease manifestations may range from a nonspecific febrile illness
      to one with severe multiorgan failure. Weil's disease is the severe form of the
      infection; which occurs in less than 10% of the patients and is associated with
      high mortality. The methods available for diagnosis and treatment of
      leptospirosis are discussed in this review. Crystalline penicillin is the drug of
      choice for treatment of leptospirosis in children. Avoidance of contact with
      flood waters and rodent control are vital for prevention of the disease. We also
      discuss the differences between childhood leptospirosis and adult disease. We
      used two methods to garner the information presented in this article: i) we
      searched the PubMed database (http://www.ncbi.nlm.nih.gov/pubmed/) using the
      keywords 'leptospirosis' and 'children,' with special emphasis given to articles
      from the Indian literature; and ii) we reviewed the chapters on leptospirosis in
      the standard textbooks of pediatric and infectious diseases.

PMID- 19770532
TI  - Thymectomy in myasthenia gravis.

PMID- 19770533
TI  - Near-infrared indocyanine green video angiography in aneurysm surgery.

PMID- 19770534
TI  - Management of hydrocephalus in patients with tuberculous meningitis.
AB  - Hydrocephalus is one of the commonest complications of tuberculous meningitis
      (TBM) occurring in up to 85% of children with the disease. It is more severe in
      children than in adults. It could be either of the communicating type or the
      obstructive type with the former being more frequently seen. The Vellore grading
      system for clinical grading of patients with TBM and hydrocephalus with grade I
      being the best grade and grade IV being the worst grade has been validated by
      several authors. The management of hydrocephalus can include medical therapy with
      dehydrating agents and steroids for patients in good grades and those with
      communicating hydrocephalus. However, surgery is required for patients with
      obstructive hydrocephalus and those in poor grades. Surgery can involve either a
      ventriculo-peritoneal shunt or endoscopic third ventriculostomy (ETV).
      Complications of shunt surgery in patients with TBM and hydrocephalus are high
      with frequent shunt obstructions and shunt infections requiring repeated
      revisions. ETV has variable success in these patients and is generally not
      advisable in patients in the acute stages of the disease. Mortality on long-term
      follow up has been reported to vary from 10.5% to 57.1% in those with altered
      sensorium prior to surgery and 0 to 12.5% in patients with normal sensorium.
      Surgery for patients in Vellore grade IV is usually associated with a poor
      outcome and high mortality and therefore, its utility in these patients is
      debatable.

PMID- 19770535
TI  - Management of the trigeminocardiac reflex: facts and own experience.
AB  - The trigeminocardiac reflex (TCR) is defined as the sudden onset of
      parasympathetic dysrhythmia, sympathetic hypotension, apnea, or gastric hyper
      motility during stimulation of any of the sensory branches of the trigeminal
      nerve. The proposed mechanism for the development of TCR is--the sensory nerve
      endings of the trigeminal nerve send neuronal signals via the Gasserian ganglion
      to the sensory nucleus of the trigeminal nerve, forming the afferent pathway of
      the reflex arc. It has been demonstrated that the TCR may occur with mechanical
      stimulation of all the branches of the trigeminal nerve anywhere along its course
      (central or peripheral). The reaction subsides with cessation of the stimulus.
      But, some patients may develop severe bradycardia, asystole, and arterial
      hypotension which require intervention. The risk factors already known to
      increase the incidence of TCR include: Hypercapnia; hypoxemia; light general
      anesthesia; age (more pronounced in children); the nature of the provoking
      stimulus (stimulus strength and duration); and drugs: Potent narcotic agents
      (sufentanil and alfentanil); beta-blockers; and calcium channel blockers. Because
      of the lack of full understanding of the TCR physiology, the current treatment
      options for patients with TCR include: (i) risk factor identification and
      modification; (ii) prophylactic measures; and (iii) administration of vagolytic
      agents or sympathomimetics.

PMID- 19770536
TI  - Restorative therapy in stroke using stem cells.
AB  - The nonregenerative capability of the injured adult brain has been challenged in
      recent years and neural plasticity has been observed experimentally in both
      global and focal brain ischemia in animal models. Whether neuro-genesis increases
      in response to brain lesions or stem cells can be used for transplantation are
      the potential questions to be answered. Functional recovery may occur in a small
      or a localized brain injury using rehabilitation measures, but for large ischemic
      strokes, the restoration may require new synaptic connections within and away
      from the damaged tissue. In an infarcted area, the ischemic core may not respond
      to any pharmacological or rehabilitative intervention. For these reasons, the
      prospects of repairing the neuron system, using cell transplantation seems
      promising and may offer a unique approach for brain repair and restoration of
      function. On going animal and human trials have greatly helped us to burgeon our
      hopes on this method of restorative therapy after stroke. The ultimate aim of any
      therapeutic strategy is the maximum restoration possible and eventual complete
      normalcy of function.

PMID- 19770538
TI  - Biomechanical analysis of multilevel discectomy and excision of posterior
      longitudinal ligament: an in vitro study in sheep.
AB  - AIM: This experimental biomechanical study was performed to determine the effects
      of multilevel anterior cervical discectomy and excision of posterior longitudinal
      ligament (PLL) to stabilize the cervical spine using an in vitro animal model.
      MATERIALS AND METHODS: Fifty fresh cadaveric C3-C6 sheep spine specimens were
      divided into five experimental groups: Group A was the control group; Group B,
      one-level discectomy; Group C, two- level discectomy, Group D, three-level
      discectomy, and Group E, three-level discectomy and excision of PLL,
      respectively. The specimens were subjected to non-destructive loads cycled from
      zero to five Newton-meter for flexion, extension, right and left lateral bending,
      and axial rotation on an electrohydraulic test machine. Load displacement curves
      were obtained via collected data using strain gauges. The values were obtained
      for all five groups, statistical differences were determined respectively
      (P<0.05, ANOVA). RESULTS: One-level discectomy was less stable than the control
      group, two-level discectomy was less stable than one-level discectomy and three
      level discectomy was less stable than two-level discectomy, respectively
      (P<0.05). Excision of PLL did not seem to affect stability (P>0.05). CONCLUSION:
      Our data suggested that cervical discectomy decreases stability of sheep spine
      pieces.

PMID- 19770537
TI  - Expression of VEGF and neural repair after alprostadil treatment in a rat model
      of sciatic nerve crush injury.
AB  - BACKGROUND: Vasoactive drug alprostadil improves microcirculation and can be
      effective in treating disorders of peripheral nerves. Vascular endothelial growth
      factor (VEGF) has been shown to have protective action in cerebral ischemia,
      disorders of spinal cord, and also peripheral nerves. However, the mechanism of
      action of VEGF in peripheral nerve injuries is uncertain. OBJECTIVES: To study
      the effect of application of alprostadil on the pathological and functional
      repair of crush nerve injuries and also the expression of VEGF. MATERIALS AND
      METHODS: Rat sciatic nerves were crushed by pincers to establish the model of
      crush injury. All of the 400 sprague dawley (SD) rats were randomly divided into:
      Control; saline; saline+VEGF-antibody; alprostadil; and alprostadil+VEGF antibody
      groups. The SPSS 11.5 software was used for statistical analysis. The expression
      of VEGF in dorsal root ganglia (DRGs), following crush injury to sciatic nerves,
      was studied by reverse transcribed-polymerase chain reaction (RT-PCR),
      immunohistochemistry, electromicroscope, and electrophysiology. The effects of
      alprostadil on expression of VEGF, repair of neural pathology, and recovery of
      neural function were also evaluated. RESULTS: We found that VEGF messenger
      ribonucleic acid (mRNA) was significantly increased in alprostadil and
      alprostadil+VEGF-antibody groups, compared to the saline and saline+VEGF antibody
      groups. The number of VEGF-positive neurons was significantly increased in the
      alprostadil group, compared to the saline, saline+VEGF antibody, and
      alprostadil+VEGF antibody groups. Besides, addition of this drug also caused less
      pathological changes in DRGs, better improvement of nerve conduction velocities
      of sciatic nerves, and more increase of toe spaces of right hind limbs of rats.
      CONCLUSIONS: The vasoactive agent alprostadil may reduce the pathological lesion
      of peripheral nerves and improve the rehabilitation of the neural function, which
      may relate to upregulation of the expression of VEGF, following crush injury to
      the peripheral nerves.

PMID- 19770539
TI  - Mid-term results of thoracoscopic thymectomy for myasthenia gravis.
AB  - CONTEXT: Video-assisted thoracic surgery (VATS) has been proposed as a less
      invasive technique for treatment of myasthenia gravis. MATERIALS AND METHODS: A
      total of 31 patients underwent a right-sided VATS to remove all anterior
      mediastinal fat and thymic tissue during a 4-year period in our institution. None
      of the patients had associated thymoma. RESULTS: All procedures were performed
      successfully with no conversion to sternotomy. The mean operating time was 190
      minutes. The median intubation time and assisted ventilation were 24 and 18
      hours, respectively. The median ICU and hospital stays were 3 and 7 days,
      respectively. The median time for post-operative chest drainage was 48 hours.
      There was no perioperative mortality. Eight significant complications occurred.
      One patient had atelectasis, 1 patient had aspiration pneumonia, and 3 patients
      had postoperative myasthenic crisis and required prolonged mechanical
      ventilation. Other complications were granuloma of the vocal cord, right
      recurrent laryngeal nerve palsy, and temporary brachial plexus injury due to poor
      intraoperative positioning. The mean length of follow-up was 20 months (range: 3
      42 months). Overall, 27 patients (87%) had improved clinically and 11 patients
      (35%) had complete remission. The resulting scars were cosmetically acceptable
      for all patients. CONCLUSION: VATS provides an effective alternative approach to
      thymectomy and has several advantages over open techniques. VATS causes minimal
      postoperative complications, shortens hospital stay, and gives better cosmetic
      results.

PMID- 19770540
TI  - Spectrum of mutations in sarcoglycan genes in the Mumbai region of western India:
      high prevalence of 525del T.
AB  - BACKGROUND: While the clinical and immunocytochemical features of
      sarcoglycanopathies have been reported from India, genetic aspects have not been
      studied. There is large variation in the sarcoglycan mutations among the studied
      populations. AIM: To study the spectrum of mutations in sarcoglycan genes (SG).
      MATERIALS AND METHODS: Patients fulfilling Bushby's criteria for limb girdle
      muscular dystrophy were prospectively analyzed. Patients gave their medical
      history and underwent a clinical examination, serum creatine kinase estimation,
      electrophysiology, muscle biopsy with immunostaining for alpha, beta, gamma, and
      delta subunits and mutational analysis using denaturing high pressure liquid
      chromatography and direct sequencing. RESULTS: Mutations in SG accounted for
      26.4% of the cohort of limb girdle muscular dystrophy. The mean age of these 18
      patients was 22.5 years. Generally, proximal weakness affected the flexor and
      adductor compartments of the lower and upper limbs. The clinical profile of
      various mutations was indistinguishable from each other. Gamma SG mutations were
      most common, seen in 8 patients, followed by delta SG mutation in 5 patients and
      alpha mutation in 4 patients, while only 1 patient had mutation in the beta
      sarcoglycan gene. The most prevalent mutation in the gamma SG gene was 525del T.
      This is of interest as the mutation has been known to exist only in specific
      populations. CONCLUSION: This study, the first mutational analysis of Indian
      patients with sarcoglycanopathies suggests gamma SG mutations were the most
      common and the most prevalent mutation in the gamma SG gene was 525del T.

PMID- 19770541
TI  - Interhemispheric interaction in the motor domain in children with cerebral palsy.
AB  - BACKGROUND: The attention of pediatric specialists has been continuously
      attracted to the problem of cerebral palsy (CP) and the formation of behavioral
      and motor skills in the initial years of life in these patients. This work aimed
      at studying the specifics of intra- and interhemispheric connections in the motor
      domain in children with CP as well as their dynamics in the process of
      rehabilitation using hand/finger synkineses and and lateral profile as markers.
      MATERIALS AND METHODS: A total of 215 children aged 4-7 years were recruited
      after obtaining their parents' consent, including 95 patients with the most
      prevalent forms of CP (spastic diplegia, hemiparetic form) who underwent complex
      treatment in a neuropsychological sanatorium and 120 healthy children from a
      kindergarten. Data were analyzed using nonparametric methods and the chi-square
      test with the help of the statistical program SPSS v.14. RESULTS: Changes in the
      scores and types of synkinesis after rehabilitation indicated that in spastic
      diplegia the assumed symmetric brain defects were associated with uniform
      restoration of interhemispheric connections and less disturbance of
      intrahemispheric connections. In hemiplegia, on the contrary, misbalance in
      intrahemispheric connections prevailed and compensation was noticed only in left
      hemispheric pathology. The magnitude, type, and improvement of hand synkineses in
      the course of treatment depended on the lateral phenotype. CONCLUSION:
      Hand/finger synkineses in CP children change with rehabilitation. The methods
      used in the study can be recommended for application in the system of medico
      biological and psycho-pedagogical monitoring of children with CP.

PMID- 19770542
TI  - Efficacy and safety of mitoxantrone, as an initial therapy, in multiple
      sclerosis: experience in an Indian tertiary care setting.
AB  - BACKGROUND AND PURPOSE: Mitoxantrone is an approved disease modifying agent for
      treatment of multiple sclerosis (MS). The aim of the study was to assess its
      efficacy and safety in Indian MS patients. MATERIALS AND METHODS: A total of 23
      patients with clinically definite MS (Poser criteria) were enrolled in an open
      label study. Of which, 21 satisfied the McDonald's criteria for MS and two
      satisfied the diagnostic criteria of neuromyelitis optica (NMO). The numbers of
      relapses and expanded disability status scale (EDSS) score were used as primary
      and secondary outcome measures. The patients were monitored for the adverse
      effects. RESULTS: In 17 (15 MS and two NMO) patients who completed one year of
      therapy, there was significant difference in the mean annual relapse rates
      [before 0.879+/-0.58; on mitoxantrone 0.091+/-0.17, (P=0.003)]. Of the 17
      patients, ten (MS 9 and NMO 1) completed therapy for two years. Annual relapse
      rates [before (1.024+/-0.59), on therapy (0.155+/-0.21), (P=0.0054)] and EDSS
      score [before start of therapy 5.3, at the end of therapy 2.4, (P=0.001)] showed
      significant benefit in the ten patients who completed two years therapy. This
      benefit persisted during the mean follow-up period of two and a half years after
      completion of therapy. The adverse events noted in the entire cohort were
      leucopenia in four patients and asymptomatic reversible decrease in cardiac
      ejection fraction in one patient. Leucopenia was severe in two patients requiring
      discontinuation of the therapy and mitoxantrone was also discontinued in the
      patient with cardiotoxicity. CONCLUSIONS: Mitoxantrone, as an initial therapy,
      decreases clinical exacerbations and disability progression, and has a reasonable
      safety profile in Indian patients with MS and NMO.

PMID- 19770543
TI  - Comparison of MRI-based thrombolysis for patients with middle cerebral artery
      occlusion<or=3 h and 3-6 h.
AB  - OBJECTIVE: To investigate the outcomes of magnetic resonance imaging (MRI)-based
      thrombolysis using recombinant tissue plasminogen activator (rt-PA) in patients
      with acute middle cerebral artery (MCA) occlusion in 3-6 hours. MATERIALS AND
      METHODS: MRI-selected patients (n=15) with acute ischemic stroke in MCA divided
      into two groups (<or=3 h and 3-6 h) were treated with intravenous rt-PA. MR was
      performed before rt-PA, at 24 hours, 7 days, and 14 days after stroke.
      Recanalization was assessed 24 h after thrombolysis, and clinical status was
      evaluated before rt-PA treatment, 6 hours, 24 hours, 7 days, and 14 days after
      thrombolysis by the National Institutes of Health Stroke Scale (NIHSS). Modified
      rankin scale (MRS) was used to assess clinical outcome at 30 and 90 days after
      thrombolysis. RESULTS: There was no significant between <or=3 h and 3-6 h group
      in length of hospital stay, recanalization, MRS, and favorable outcome at 90
      days. Recanalization within 24 hours occurred in 9 (60%), and nonrecanalization
      in 6 (40%). One patient in recanalization group and three in nonrecanalization
      group had an asymptomatic intracranial hemorrhage (ICH) within 24 h after
      thrombolysis (P=0.235). Recanalization with thrombolysis was associated with a
      better outcome regardless of the time point of rt-PA treatment. Comparison with
      nonrecanalization group, recanalization was also associated with a lower NIHSS
      score at 14 days (P=0.003), a lower TIMI grade at 7 days (P<0.001), and a shorter
      length of hospital stay (P=0.018). CONCLUSION: Our study suggested that MR-based
      thrombolysis using rt-PA was safe and reliable in patients with acute MCA
      occlusion in 3-6 hours.

PMID- 19770544
TI  - Etiological factors of traumatic peripheral nerve injuries.
AB  - BACKGROUND: Traumatic injury of peripheral nerves is a worldwide problem and can
      result in significant disability. Management of peripheral nerve injuries (PNIs)
      requires accurate localization and the assessment of severity of the lesion. AIM:
      The purpose of this study is to analyze the data of patients with PNIs referred
      for electromyography to a tertiary care hospital. MATERIALS AND METHODS: This is
      a retrospective study of clinical and electromyographic data of patients with
      PNIs seen over a period of eight-years (1999-2007) in a tertiary hospital. The
      data collected included: Demographic data, cause, type of lesion, anatomical
      location of the lesion, and the mechanism of lesion. RESULTS: During the study
      period 938 patients were seen with nerve injuries and the distribution of nerve
      injuries was: PNIs: 1,165; brachial plexus lesions: 76; and lumbar plexus
      lesions: 7. The mean age was 31.8 years (range 2-81 years) and the male to female
      ratio was 2.4:1. The most frequent nerve injuries were ulnar nerve in the upper
      extremity and sciatic nerve in the lower extremity. The most common cause of
      nerve injury was motor vehicle accidents. Two-thirds of the PNIs were partial.
      CONCLUSION: This study can serve as a guide to determine the epidemiology and
      classification of traumatic peripheral and plexus injuries.

PMID- 19770545
TI  - Fronto-temporo-orbitozygomatic craniotomy and "half-and-half" approach for
      basilar apex aneurysms.
AB  - BACKGROUND: Basilar apex aneurysms (BAA) are located in interpeduncular cistern
      surrounded by eloquent neurovascular structures. Surgical access is difficult due
      to narrow surgical corridors and requires traversing through a depth of 6-8 cm of
      subarachnoid space. AIM: Surgical management of BAAs clipped using frontotemporal
      craniotomy, orbitozygomatic osteotomy with combined subtemporal and transylvian
      (half and half) approach is discussed. SETTING AND DESIGN: Tertiary care referral
      institute; prospective study. MATERIALS AND METHODS: Five patients with BAA
      rupture causing subarachnoid hemorrhage presented in modified Hunt and Hess (Hand
      H) grades II (n=1), III (n=1) and IV (n=3), respectively. In 4 patients, the
      aneurysms were 0.8-1.2 cm in diameter, situated 7 mm-1 cm above dorsum sellae.
      Two of them had posteriorly projecting aneurysms. One patient had a giant, high
      BAA with a left parietooccipital arteriovenous malformation. Vasospasm of
      posterior cerebral/proximal basilar artery was seen in 2 patients. In one
      patient, internal carotid artery was mobilized by intradural anterior clinoid
      drilling with carotid collar division. Triple-H therapy was administered
      following surgery. RESULTS: There was no intraoperative rupture or temporary
      clipping. Follow up angiography showed complete aneurysmal obliteration with
      preservation of posterior cerebral and superior cerebellar arteries. Follow up
      (mean: 8.7+/-3.5 months) H and H grades were II (n=2) and III (n=3),
      respectively. The morbidity include caudate and thalamic region infarct,
      transient III rd nerve palsy and cerebrospinal fluid otorrhoea (n=1,
      respectively). CONCLUSIONS: This simple approach provides a wide surgical
      corridor from 5 mm below to greater than 1 cm above dorsum sellae with adequate
      proximal control of basilar artery. It is an option to endovascular embolization
      especially with large and giant, or wide-necked BAA, vertebrobasilar tortuosity,
      coil compaction or postcoiling re-rupture and an associated large haematoma.

PMID- 19770546
TI  - Suboccipital segment of the vertebral artery: a cadaveric study.
AB  - OBJECTIVE: To study the course, relationships, branches and possible anomalies of
      the vertebral artery in the suboccipital region in adult Indian cadavers.
      MATERIALS AND METHODS: Twenty-one suboccipital segment vertebral artery specimens
      from embalmed, Indian adult cadavers were dissected and studied. Dissection was
      performed using microsurgical instruments and was carried out from the skin up to
      the vertebral artery in layers. The course, relationships and the branches of the
      vertebral artery were studied and measurements were taken using Vernier calipers.
      The readings obtained were corroborated with the measurements derived from the
      digital images using a computer. OBSERVATIONS: All the vertebral arteries had a
      tortuous course and were covered with rich venous plexuses. None of the specimens
      had an anomalous course. The artery was divided into a vertical segment (Vv)
      between C2 and C1 vertebra and a horizontal segment (Vh) from the C1 transverse
      foramina to its dural entry. The mean diameter of the artery was 4.8 mm. The
      shortest distance of Vv segment from the dural tube was 16.1 mm, and the distance
      from the C2 ganglion was 7.2 mm. The average length of the Vv segment was 15 mm
      and the average length of the Vh segment was 35.6 mm. The average of the shortest
      distance between the vertebral artery and the midline was 13.4 mm. CONCLUSION:
      The vertebral artery has a tortuous course and is prone to accidental iatrogenic
      injury, which can result in devastating neurological sequelae depending on
      contralateral vertebral artery flow. A thorough anatomical knowledge of this
      segment is essential for the surgeon who intends to operate in this area.

PMID- 19770548
TI  - Pyridoxine-dependent seizures: 10-year follow-up of eight cases.
AB  - Eight children with pyridoxine-dependent seizures (PDS) were seen over a period
      of 10 years. Of those children, 6 are on regular follow-up. Four of the children
      were seen in one family. All the patients presented with refractory seizures,
      mainly neonatal status epilepticus. Though PDS is a rare condition, it must be
      considered in all cases with refractory seizures, particularly in children
      younger than 3 years. When confirming a diagnosis, oral pyridoxine is as
      effective as intravenous pyridoxine.

PMID- 19770547
TI  - Assessment of microscope-integrated indocyanine green angiography during
      intracranial aneurysm surgery: a retrospective study of 120 patients.
AB  - AIMS: The purpose of this study was to assess the clinical value of indocyanine
      green angiography (ICG) in intracranial aneurysm surgery by comparing the
      findings with postoperative angiographic results. MATERIALS AND METHODS: One
      hundred and twenty patients with 148 intracranial aneurysms were included. ICG
      angiography was performed before and/or after the aneurysm clipping. A near
      infrared excitation light illuminated the operation field, ICG was injected
      intravenously. The intravenous fluorescence was imaged with a video camera
      integrated into the microscope. RESULTS: A total of 208 investigations of ICG
      angiography were performed. Aneurysm clipping was applied in 120 patients.
      Incomplete clipping was detected in four patients. Parent and/or branching artery
      stenosis was found in five patients. Delayed perfusion of ICG was detected in one
      patient. Postoperative digital subtraction angiography (DSA) was performed in 108
      patients. The postoperative angiographic results were consistent with findings on
      intraoperative ICG angiograms in 100 patients (92.6%). In three cases, a mild
      stenosis was seen on DSA, which was not detected intraoperatively using ICG
      angiogram. In one patient, middle cerebral artery stenosis was found. Three
      patients had small residual aneurysms found by postoperative DSA. The remaining
      one developed a severe cerebral vasospasm. CONCLUSIONS: ICG angiography is a
      simple, reliable and cost-effective method. It provides real-time information in
      detecting the patency of parent, branching, perforating arteries and residual
      aneurysm. This technique may be a useful adjunct to improve the quality of
      intracranial aneurysm surgery.

PMID- 19770549
TI  - Challenges in neurosurgical intraoperative consultation.
AB  - BACKGROUND: Intraoperative consultation for neurosurgical specimens can be
      difficult at times, despite the use of both frozen section and squash
      preparation. Various factors influence the diagnostic accuracy of these
      procedures. This study was conducted to evaluate reasons for discordant case
      results in neurosurgical intraoperative consultations and make a comparative
      analysis of these two commonly used methods to identify the possible pitfalls,
      errors, and limitations. MATERIALS AND METHODS: All the neurosurgical cases
      received in the Department of Pathology for intraoperative consultation over a
      period of 3 years were studied retrospectively. The slides of frozen sections and
      squash preparation were retrieved and the diagnosis was compared with the final
      diagnosis given on paraffin-embedded sections. RESULTS AND OBSERVATIONS: A total
      of 6% of the cases were found to be discordant; these included angiomatous
      meningioma, Non-Hodgkins lymphoma, metastatic renal cell carcinoma,
      cerebellopontine angle fibrous meningioma, and craniopharyngioma. Highly vascular
      lesions, unavailability of squash preparation in a few cases and technical errors
      like thick smears, excessively crushed specimen, freezing, and cautery induced
      and crushing artifacts contributed to misdiagnosis. CONCLUSION: The discrepant
      cases need to be reviewed regularly by pathologists to familiarize themselves
      with the morphological changes and artifacts. The knowledge of possible errors
      could minimize misinterpretation and help in providing a more conclusive opinion
      to the operating surgeon.

PMID- 19770550
TI  - Rib head disarticulation for multilevel transpedicular thoracic corpectomies and
      expandable cage reconstruction.
AB  - Traditional posterior approaches to the thoracic spine are done with either costo
      transversectomy, lateral extracavitary approaches, or transpedicular approaches.
      The transpedicular approach is the only one that preserves the rib head. However,
      placing an expandable cage with this rib head intact poses special challenges
      because of the narrow corridor defined by the rib head and the spinal cord.
      Instead of removing the rib head, which requires pleural dissection and carries
      the risks of pleural injury, we disarticulate it and push it laterally during
      cage placement. This avoids pleural dissection and affords expandable cage
      placement through a transpedicular approach.

PMID- 19770551
TI  - Evaluation of nine children with reversible posterior encephalopathy syndrome.
AB  - BACKGROUND: Reversible posterior leukoencephalopathy syndrome (PRES) is a
      neurological disorder characterized by signs of posterior cerebral edema upon
      radiographic examination. MATERIALS AND METHODS: We retrospectively analyzed the
      records of nine children with the diagnosis of PRES. RESULTS: Of the nine
      patients, seven were receiving immunosuppressive therapy and two were acute
      hypertensive crisis associated with renal disease. Immunosupressive drugs were
      intrathecal methotrexate in two patients, cyclosporine in two patients,
      intrathecal cytarabine in one patient, cyclophasphamide in one patient, and
      intravenous immunoglobulin (IVIg) in another one patient. The most presenting
      symptoms were seizure, headache, and altered consciousness. Six patients had
      seizures. Altered consciousness was present in four patients. Headache and nausea
      or vomiting was present also in six patients. Visual abnormalities were noted in
      two patients. Magnetic resonance imaging (MRI) studies showed white-matter
      abnormalities suggestive of edema in the posterior regions of the cerebral
      hemispheres, but the changes often involved other cerebral areas, the brain stem,
      basal ganglia or the cerebellum. The patients were treated with antihypertensive
      medications, and immunosuppressive therapy was withdrawn. In all the patients,
      the clinical and radiological findings resolved more completely. CONCLUSION:
      Reversible posterior leukoencephalopathy may develop in patients who have renal
      insufficiency or hypertension or who are immunosuppressed. This syndrome should
      be recognized immediately and trigger agents can be discontinued to prevent long
      term sequelae.

PMID- 19770552
TI  - Acute ischemic infarct in the middle cerebral artery territory following a
      Russell's viper bite.
AB  - Ischemic stroke following snake bite is rare. We report an 18-year male who
      developed right hemiplegia with expressive aphasia following a Russell's viper
      bite. T2-weighted magnetic resonance imaging revealed infarct in the left middle
      cerebral artery territory. The possible mechanisms for cerebral infarction in
      this scenario include disseminated intravascular coagulation, toxin induced
      vasculitis and endothelial damage.

PMID- 19770553
TI  - Recovery of cognitive dysfunction in a case of delayed encephalopathy of carbon
      monoxide poisoning after treatment with donepezil hydrochloride.
AB  - Delayed encephalopathy following carbon monoxide poisoning is a serious
      complication. Here, we report a patient with delayed encephalopathy who suffered
      from cognitive disorders and urinary incontinence after a temporal normal period
      of 15 days after acute intoxication, and his cognitive function recovered
      gradually following donepezil hydrochloride treatment. Now, he can undertake
      slight farming work.

PMID- 19770554
TI  - Complete posterior migration of intact vertebral body in spinal tuberculosis.
AB  - Spinal tuberculosis most commonly presents as a paradiscal lesion involving the
      disc space and adjacent vertebral bodies. Atypical forms of spinal tuberculosis
      have been described and are most often a result of posterior element involvement.
      The authors report a patient, who presented with complete posterior migration of
      an intact vertebral body, a complication of spinal tuberculosis that has not been
      reported till date. A 12-year-old girl with history of pulmonary tuberculosis
      presented with progressive paraparesis and back pain. Plain X-rays and MRI
      revealed that the L2 vertebral body had migrated posteriorly into the spinal
      canal, without significant movement of the posterior elements. The vertebral body
      was normal, with no erosion or bone loss. However, bilateral pedicle and facet
      joint involvement was seen. The neural elements were decompressed through an
      anterolateral retroperitoneal approach and the spine reconstructed. The authors
      present this rare manifestation of spinal tuberculosis and discuss the possible
      mechanisms of this presentation.

PMID- 19770555
TI  - Choroid plexus papilloma presenting as a non-contrast-enhancing fourth
      ventricular mass in a child.
AB  - Choroid plexus papilloma (CPP) is a rare benign tumor of the central nervous
      system with a propensity for location within the lateral ventricle in children.
      We report a case of a 14-year-old girl who presented with transient facial
      paresis and ataxia. Her imaging showed a non-enhancing intra fourth ventricular
      mass, the histology of which was reported as CPP. The atypical clinical and
      radiological features in this case are discussed. Choroid plexus papillomas
      should be considered in the differential diagnosis of non-enhancing fourth
      ventricular masses.

PMID- 19770556
TI  - Brain abscess and granuloma formation as late complications of retained
      ventricular catheter.
AB  - This report presents a rare complication of ventriculoperitoneal shunt, delayed
      development of brain abscess and foreign body granuloma formation adjacent to the
      intraventricular catheter. Both the complications occurring in the same patient
      is unusual.

PMID- 19770557
TI  - Reactive changes of disc space and foreign body granuloma due to bone wax in
      lumbar spine.
AB  - Bone wax is a well-known agent used to prevent bleeding from the bone that can be
      used in different surgical procedures. Bone wax is a safe agent, but it may
      rarely lead to significant foreign body reactions. In this report, we present a
      patient who developed bone wax-related disc space foreign body granuloma
      following L4 total laminectomy, extremely rare complication.

PMID- 19770558
TI  - Posterior reversible encephalopathy syndrome in systemic lupus erythematosus.

PMID- 19770559
TI  - A single fatal dose of olanzapine.

PMID- 19770560
TI  - Midbrain infarct presenting as isolated medial rectus palsy.

PMID- 19770561
TI  - Imaging of spontaneous neuromagnetic activity in a patient with internal carotid
      artery stenosis.

PMID- 19770562
TI  - A case of sporadic periodic hypokalemic paralysis with atypical features:
      recurrent differential right brachial weakness and cognitive dysfunction.

PMID- 19770563
TI  - Long-term effects of antiepileptic therapy on cardiovascular risk factors in
      children.

PMID- 19770565
TI  - Hypertrophic olivary degeneration: the forgotten triangle of Guillain and
      Mollaret.

PMID- 19770564
TI  - Choriocarcinoma with arterial and venous thrombosis.

PMID- 19770566
TI  - Narcolepsy an often missed diagnosis: first documented case from India.

PMID- 19770567
TI  - Facial palsy caused by mumps parotitis.

PMID- 19770568
TI  - Spinal epidural hematoma after insertion of a thoracic epidural catheter in the
      absence of coagulation disorders--a call for raised awareness.

PMID- 19770569
TI  - Spontaneous cerebrospinal fluid rhinorrhea: a rare initial presentation of clival
      chordoma.

PMID- 19770570
TI  - Posterior communicating artery aneurysm associated with duplicated posterior
      communicating artery and bilateral fetal posterior cerebral arteries.

PMID- 19770571
TI  - Pure cortical supratentorial extraventricular ependymoma.

PMID- 19770572
TI  - D-dimer is useful in the diagnosis of cortical venous sinus thrombosis.

PMID- 19770573
TI  - Aortic aneurysm presenting as conus-cauda syndrome.

PMID- 19770574
TI  - Extensive meningeal and prenchymal calcified tuberculoma as long-term residual
      sequelae of tuberculous meningitis.

PMID- 19770575
TI  - Parkinson disease, LRRK2 and the endocytic-autophagic pathway.
AB  - Neurons are quiescent cells that survive for several decades, many times the
      turnover time of most organelles and proteins, and so with advancing age neurons
      become affected by degenerative diseases. Autophagy is thought to be an important
      cellular mechanism preventing cell degeneration in such long-lived cells. We have
      recently found that the Parkinson disease (PD) gene leucine rich repeat kinase 2
      (LRRK2) is directly involved in this process by acting as a negative regulator of
      autophagic activity. We created a novel genomic DNA reporter cellular model using
      a new recombineering strategy called Sequential insertion of Target with
      ovErlapping Primers (STEP) to express a genomic DNA locus YPet-LRRK2 fusion
      protein. Expression of the R1441C mutant form of LRRK2 induces a cellular
      phenotype of impaired autophagic balance at the convergent crossroads of the
      endocytic and autophagic avenues. Conversely, RNAi-induced knockdown of LRRK2
      increases autophagic activity. Taken together, these data demonstrate the key
      role of LRRK2 in regulating autophagy and suggest modulation of LRRK2 function
      may represent a promising therapeutic target to help restore autophagic
      equilibrium in neurodegenerative diseases.

PMID- 19770576
TI  - Sorafenib induces preferential apoptotic killing of a drug- and radio-resistant
      Hep G2 cells through a mitochondria-dependent oxidative stress mechanism.
AB  - Sorafenib (Nexavar, BAY43-9006), a bi-arylurea, is a newly established anti
      cancer drug and its functional attribute of cytotoxicity is based on the multi
      kinase inhibitory action. Here, we report yet another novel pathway in which
      sorafenib can induce apoptotic cell death preferentially and efficaciously on an
      experimentally proven drug- and radio-resistant human Hep G2 cells via a
      mitochondria-dependent oxidative stress mechanism. A real time confocal imaging
      assay revealed that sorafenib could rapidly provoke the production of ROS
      plethorically, mainly concentrating in the mitochondria, albeit substantial
      amounts of ROS could also be detected in cytosol and nucleus. The rapid
      production of ROS could simultaneously induce intracellular glutathione (iGSH)
      depletion. A nearly 90% of iGSH was found to be depleted in 1h period after the
      cells received the drug treatment. Besides mitochondria, iGSH depletion could
      also be detected in other cellular compartment including cytoplasm and nucleus.
      Interestingly, we also demonstrated that sorafenib could trigger mitochondrial
      Ca(2+) overload. All these events compoundedly serve as the final arbitrator to
      initiate lethal apoptotic process through the release of cytochrome c and caspase
      3/7 activation. Collectively, we provide first evidence here that sorafenib can
      provoke an alternative pathway for apoptosis induction of Hep G2 cells through a
      mitochondria-dependent oxidative stress mechanism which is independent of
      original kinase inhibitory attribute of the drug action. Most importantly, we
      also demonstrate that sorafenib can effectively eradicate a highly drug- and
      radio-resistant HCC cells. Thus, our data can provide the basis for a potential
      applicability of sorafenib in a combined treatment modality.

PMID- 19770578
TI  - Replication timing: findings from fibers.

PMID- 19770577
TI  - Requirements of Hsp104p activity and Sis1p binding for propagation of the
      [RNQ(+)] prion.
AB  - The formation and maintenance of prions in the yeast Saccharomyces cerevisiae is
      highly regulated by the cellular chaperone machinery. The most important player
      in this regulation is Hsp104p, which is required for the maintenance of all known
      prions. The requirements for other chaperones, such as members of the Hsp40 or
      Hsp70 families, vary with each individual prion. [RNQ(+)] cells do not have a
      phenotype that is amenable to genetic screens to identify cellular factors
      important in prion propagation. Therefore, we used a chimeric construct that
      reports the [RNQ(+)] status of cells to perform a screen for mutants that are
      unable to maintain [RNQ(+)]. We found eight separate mutations in Hsp104p that
      caused [RNQ(+)] cells to become [rnq(-)]. These mutations also caused the loss of
      the [PSI(+)] prion. The expression of one of these mutants, Hsp104p-E190K, showed
      differential loss of the [RNQ(+)] and [PSI(+)] prions in the presence of wild
      type Hsp104p. Hsp104p-E190K inefficiently propagated [RNQ(+)] and was unable to
      maintain [PSI(+)]. The mutant was unable to act on other in vivo substrates, as
      strains carrying it were not thermotolerant. Purified recombinant Hsp104p-E190K
      showed a reduced level of ATP hydrolysis as compared to wild type protein. This
      is likely the cause of both prion loss and lack of in vivo function. Furthermore,
      it suggests that [RNQ(+)] requires less Hsp104p activity to maintain
      transmissible protein aggregates than Sup35p. Additionally, we show that the L94A
      mutation in Rnq1p, which reduces its interaction with Sis1p, prevents Rnq1p from
      maintaining a prion and inducing [PSI(+)].

PMID- 19770579
TI  - Selectively killing transformed cells through proteasome inhibition.

PMID- 19770580
TI  - c-Myc and telomerase activation.

PMID- 19770581
TI  - Green tea (-)-epigalocatechin-3-gallate inhibits KIT activity and causes caspase
      dependent cell death in gastrointestinal stromal tumor including imatinib
      resistant cells.
AB  - Imatinib, a selective tyrosine kinase inhibitor, has been used as a standard
      first-line therapy for gastrointestinal stromal tumor (GIST) patients.
      Unfortunately, most patients responding to imatinib will eventually exhibit the
      resistance, the cause of which is not fully understood. The serious clinical
      problems of imatinib-resistance demand alternative treatment strategy. (-)
      Epigallocatechin-3-gallate (EGCG), a main component of green tea catechin, has
      been demonstrated potential anti-tumor effects on various types of cancer cells.
      Here, we report for the first time that EGCG has shown anti-tumor effects on
      gastrointestinal stromal tumor cell line GIST-T1 by suppressing cell
      proliferation and eventually inducing cell death via caspase-dependent pathways.
      GIST-T1 and imatinib resistant GIST-T1 (GIST-T1 IR) cells were used to assess the
      effects of EGCG. In both cell types, KIT activity was completely inhibited after
      4 h treatment with 60 muM EGCG. EGCG specifically inhibited activated KIT, which
      was demonstrated by using Ba/F3 cells transfected with human wild-type KIT
      construct. At a dose of 30 muM EGCG, the KIT activity remains but at more than 40
      muM EGCG, the KIT activity was abolished in these transfected-Ba/F3 cells. Our
      results suggest that EGCG has a promising potential as a natural KIT inhibitor
      and therefore it could be used as a novel therapeutic or preventive reagent for
      GISTs including the imatinib-resistant cases.

PMID- 19770582
TI  - Delivery of short hairpin RNAs by transkingdom RNA interference modulates the
      classical ABCB1-mediated multidrug-resistant phenotype of cancer cells.
AB  - Delivery of RNA interference (RNAi)-mediating agents to target cells is one of
      the major obstacles for the development of RNAi-based therapies. One strategy to
      overcome this barrier is transkingdom RNAi (tkRNAi). This technology uses non
      pathogenic bacteria to produce and deliver therapeutic short hairpin RNA (shRNA)
      into target cells to induce RNAi. In this study, the tkRNAi approach was used for
      modulation of the "classical" ABCB1-mediated multidrug resistance (MDR) in human
      cancer cells. Subsequent to treatment with anti-ABCB1 shRNA expression vector
      bearing E. coli, MDR cancer cells (EPG85 257RDB) showed 45% less ABCB1 mRNA
      expression. ABCB1 protein expression levels were reduced to a point at which
      merely a weak band could be detected. Drug accumulation was enhanced 11-fold, to
      an extent that it reached 45% of the levels in non-resistant cells and resistance
      to daunorubicin was decreased by 40%. The data provide the proof-of-concept that
      tkRNAi is suitable for modulation of "classical" MDR in human cancer cells.
      Overall, the prototype tkRNAi system tested here did not yet attain the levels of
      gene silencing seen with conventional siRNAs nor virally delivered shRNAs; but
      the tkRNAi system for gene-silencing of ABCB1 is still being optimized, and may
      become a powerful tool for delivery of RNAi effectors for the reversal of cancer
      MDR in future.

PMID- 19770583
TI  - Autophagy, senescence and tumor dormancy in cancer therapy.
AB  - The relationships between autophagy and apoptosis have been examined quite
      extensively and have often been shown to be reciprocally regulated responses to
      stresses such as exposure of tumor cells to chemotherapeutic drugs and radiation.
      However, there is now evidence that autophagy may also play a role in tumor
      dormancy. Given that tumor dormancy and disease recurrence are poorly understood
      phenomena which are nevertheless critical elements of patient morbidity and
      mortality, this commentary develops the postulate that autophagy and senescence
      may be coupled responses that influence the capacity of the tumor cell to
      maintain a prolonged state of growth arrest that can be succeeded by tumor
      regrowth and disease recurrence.

PMID- 19770584
TI  - Endocytosis and mitosis: a two-way relationship.
AB  - Cell division involves a vast remodelling of cellular membranes. This is most
      apparent for the cell surface, but it is also true for internal vesicular
      organelles such as the Golgi apparatus. while the contribution of endocytosis to
      membrane trafficking and signal processing in interphase cells is well
      established, the role of the endocytic system in cell division has long been
      neglected. A number of recent studies have however shed novel light on this
      issue. Here, we review findings supporting the existence of two important links
      between endocytosis and mitosis: First, endocytic trafficking is essential to
      reshape the plasma membrane during cell division. Second, cell division affects
      the partitioning, the trafficking and hence the activity of the signalling
      molecules that are contained within endocytic compartments.

PMID- 19770586
TI  - Self-consuming innate immunity in Arabidopsis.
AB  - Programmed cell death (PCD) associated with the pathogen-induced hypersensitive
      response (HR) is a hallmark of plant innate immunity. HR PCD is triggered upon
      recognition of pathogen effector molecules by host immune receptors either
      directly or indirectly via effector modulation of host targets. However, it has
      been unclear by which molecular mechanisms plants execute PCD during innate
      immune responses. We recently examined HR PCD in autophagy-deficient Arabidopsis
      knockout mutants (atg) and find that PCD conditioned by one class of plant innate
      immune receptors is suppressed in atg mutants. Intriguingly, HR triggered by
      another class of immune receptors with different genetic requirements is not
      compromised, indicating that only a specific subset of immune receptors engage
      the autophagy pathway for HR execution. Thus, our work provides a primary example
      of autophagic cell death associated with innate immune responses in eukaryotes as
      well as of prodeath functions for the autophagy pathway in plants.

PMID- 19770585
TI  - The hypoxic microenvironment maintains glioblastoma stem cells and promotes
      reprogramming towards a cancer stem cell phenotype.
AB  - Glioblastomas are highly lethal cancers that contain cellular hierarchies with
      self-renewing cancer stem cells that can propagate tumors in secondary transplant
      assays. The potential significance of cancer stem cells in cancer biology has
      been demonstrated by studies showing contributions to therapeutic resistance,
      angiogenesis and tumor dispersal. We recently reported that physiologic oxygen
      levels differentially induce hypoxia inducible factor-2alpha (HIF2alpha) levels
      in cancer stem cells. HIF1alpha functioned in proliferation and survival of all
      cancer cells but also was activated in normal neural progenitors suggesting a
      potentially restricted therapeutic index while HIF2alpha was essential in only in
      cancer stem cells and was not expressed by normal neural progenitors
      demonstrating HIF2alpha is a cancer stem cell specific target. We now extend
      these studies to examine the role of hypoxia in regulating tumor cell plasticity.
      We find that hypoxia promotes the self-renewal capability of the stem and non
      stem population as well as promoting a more stem-like phenotype in the non-stem
      population with increased neurosphere formation as well as upregulation of
      important stem cell factors, such as OCT4, NANOG and c-MYC. The importance of
      HIF2alpha was further supported as forced expression of non-degradable HIF2alpha
      induced a cancer stem cell marker and augmented the tumorigenic potential of the
      non-stem population. This novel finding may indicate a specific role of HIF2alpha
      in promoting glioma tumorigenesis. The unexpected plasticity of the non-stem
      glioma population and the stem-like phenotype emphasizes the importance of
      developing therapeutic strategies targeting the microenvironmental influence on
      the tumor in addition to cancer stem cells.

PMID- 19770587
TI  - Alphavirus M1 induces apoptosis of malignant glioma cells via downregulation and
      nucleolar translocation of p21WAF1/CIP1 protein.
AB  - Alphavirus, a genus of arthropod-borne togavirus, is well-known for its pro
      apoptotic capability. However, the underlying mechanism remains to be further
      clarified. Here, we have identified that M1, an alphavirus isolated in 1960s,
      targeted C6 malignant glioma cells for apoptosis. Flow cytometry analysis showed
      that more cells enter S-phase post M1 infection, and subsequently undergo a
      classic apoptosis. To elucidate the mechanism of S-phase arrest and its
      relationship to apoptosis, we tested the expression of several critical cell
      cycle regulatory proteins and found elevated phosphorylation of cyclin-dependent
      kinase 2 (CDK2), decreased expression of cyclin A and proliferating cell nuclear
      antigen (PCNA). Notably, the protein level of p21(WAF1/CIP1) was downregulated
      earliest and most effectively among all tested changes of cell cycle regulators,
      though its mRNA level was strongly upregulated. To evaluate the role of
      p21(WAF1/CIP1) in S-phase accumulation and subsequent apoptosis, we confirmed
      that exogenous p21(WAF1/CIP1) overexpression or treatment with roscovitine (a
      selective chemical inhibitor of CDK2) efficiently protected against apoptosis
      with a reduced S-phase accumulation. Thus, it is indicated that the
      downregulation of p21(WAF1/CIP1) mediated C6 apoptosis via overactivation of
      CDK2. In addition, confocal microscopy showed that p21(WAF1/CIP1) totally
      translocated to nucleolus during M1-induced C6 apoptosis. Altogether,
      downregulation and nucleolar translocation of the p21(WAF1/CIP1) protein played
      an active role in M1-induced C6 apoptosis.

PMID- 19770588
TI  - Hypoxia, angiogenesis and cancer therapy: to breathe or not to breathe?
AB  - As an expanding tumor conquers space within the host, it calls out for an
      increased oxygen supply. This demand is rarely matched by tumor blood vessels
      because neo-angiogenesis generates a structurally aberrant and functionally
      impaired vasculature. As a result of this unbalance, tumor progression is
      invariably associated with cancer cell hypoxia. Insufficient oxygenation appears
      to have opposing effects on cancer biology: on one hand, it limits tumor cell
      division; on the other, it selects for more malignant cells and it induces a
      series of cellular adaptations that sustain and foster tumor invasion. When
      designing a therapeutic strategy, how should we resolve this dichotomy? Should we
      cut oxygen supply, thereby halting neoplastic expansion, or should we let the
      tumor breathe, in order to prevent its malignant conversion?

PMID- 19770589
TI  - A landmark protein essential for mitophagy: Atg32 recruits the autophagic
      machinery to mitochondria.
AB  - Degradation of mitochondria is a fundamental process conserved from yeast to
      humans that utilizes the machinery of autophagy. In contrast to starvation
      induced, nonselective autophagy responsible for nutrient recycling, selective
      autophagy, which involves particular cues and receptors required for induction
      and cargo recognition, respectively, mediates mitochondria-specific breakdown.
      Although numerous studies highlight that mitochondria autophagy (mitophagy)
      contributes to homeostatic control of mitochondria, the molecular mechanisms
      underlying this selective clearance process are poorly understood. Using a genome
      wide visual screen, we identified Atg32, a protein essential for mitophagy in
      budding yeast. During respiratory growth, Atg32 is highly expressed, likely in
      response to oxidative stress, and anchored on the surface of mitochondria. We
      also demonstrate that Atg32 interacts with Atg8 and Atg11, proteins critical for
      recognition of cargo receptors. Notably, Atg32 contains WXXI/L/V, a conserved
      motif that serves as a binding site for the Atg8 family members. Our recent
      findings suggest that Atg32 is a transmembrane receptor that directs
      autophagosome formation to mitochondria.

PMID- 19770590
TI  - Autophagy and access: understanding the role of androgen receptor subcellular
      localization in SBMA.
AB  - Ridding neurons of toxic misfolded proteins is a critical feature of many
      neurodegenerative diseases. We have recently reported that lack of access of
      nuclear polyglutamine-expanded androgen receptor (AR) to the autophagic
      degradation pathway is a critical point in pathogenesis. When mutant AR is
      contained within the cytoplasm, it can be degraded by autophagy, resulting in
      amelioration of its toxic effects, as has been observed in other polyglutamine
      expansion diseases involving cytoplasmic mutant proteins. However, we have also
      found that pharmacological induction of autophagy protects SBMA motor neurons
      from the toxic effects of even nuclear localized mutant AR, albeit without
      affecting mutant nuclear AR levels. Thus, we have further investigated the
      mechanism by which autophagy elicits therapeutic benefit in cell culture. We
      found that endogenous autophagy only slightly alters nuclear mutant AR
      aggregation compared to substantial effects on cytoplasmic AR aggregation.
      Interestingly, pharmacological activation of mTOR-dependent autophagy did not
      significantly alter nuclear AR aggregation, whereas we observed that it protects
      SBMA motor neurons. Our findings indicate that therapeutic intervention to induce
      autophagy represents a potential potent benefit for SBMA, and that it likely does
      so by protecting SBMA motor neurons independent of a direct effect on mutant AR.

PMID- 19770591
TI  - Molecular mechanisms of necrosis in glioblastoma: the role of glutamate
      excitotoxicity.
AB  - Glioblastomas continue to rank among the most lethal primary human tumors.
      Despite treatment with the most rigorous surgical interventions along with the
      most optimal chemotherapeutic and radiation regimens, the median survival is just
      12-15 mo for patients with glioblastoma. Among the histological hallmarks of
      glioblastoma, necrosis has been demonstrated to be a powerful predictor of poor
      patient prognosis. Over the years, there have been many advances in our
      understanding of the molecular mechanisms underlying glioblastoma formation, yet
      the mechanisms that lead to tumor necrosis remain unclear. One pathway that may
      lead to necrosis in glioblastoma involves the neurotransmitter, glutamate, which
      has been shown to accumulate in the peritumoral fluid as a result of decreased
      cellular uptake by glioblastoma cells. This accumulation leads to subsequent
      glutamate excitotoxicity and probable necrosis through a massive elevation of
      intracellular Ca(2+) and reduction in cellular ATP levels. We propose that a
      pathway involving tumor necrosis factor-alpha (TNFalpha), astrocyte-elevated gene
      1 (AEG-1) and nuclear factor-kappaB (NFkappaB) leads to decreased glutamate
      uptake through coordinated downregulation of the excitatory amino acid
      transporter 2 (EAAT2), the glutamate transporter responsible for the majority of
      glutamate uptake in the human brain. In addition, we suggest that AEG-1
      signaling, loss of phosphatase and tensin homolog (PTEN), and ionotropic
      glutamate receptor activity lead to AKT pathway activation, which results in
      nutrient overconsumption and necrosis. Together, these pathways provide a new
      perspective on glioblastoma necrosis involving the process of glutamate
      excitotoxicity. Future research should address the components of these molecular
      pathways in order to better understand the mechanism of necrosis in glioblastoma
      and to begin to develop targeted therapies that may improve patient prognosis in
      the future.

PMID- 19770592
TI  - Hexokinase II detachment from the mitochondria potentiates cisplatin induced
      cytotoxicity through a caspase-2 dependent mechanism.
AB  - Cancer cells are frequently glycolytic and overexpress hexokinase II (HXK II). In
      cancer cells, the majority of hexokinase II is localized to the mitochondria
      through interaction with the voltage dependent anion channel (VDAC). Disruption
      in the binding of hexokinase II to the mitochondria has been shown to promote
      mitochondrial injury provoked by pro-apoptotic proteins. The present study
      demonstrates that cisplatin induces the PIDD (p53 induced protein with a death
      domain) dependent activation of caspase-2. In turn, caspase-2 cleaves and
      activates Bid, resulting in the oligomerization of Bak and the release of
      cytochrome c. Notably, the detachment of hexokinase II from the mitochondria
      markedly potentiates the onset of caspase-2 induced mitochondrial damage, thus
      resulting in a synergistic induction of cisplatin induced cytotoxicity.

PMID- 19770593
TI  - Chipping away at gamma-H2AX foci.
AB  - The mammalian histone H2AX protein functions as a dosage-dependent genomic
      caretaker and tumor suppressor. Phosphorylation of H2AX to form gamma-H2AX in
      chromatin around DNA double strand breaks (DSBs) is an early event following
      induction of these hazardous lesions. For a decade, mechanisms that regulate H2AX
      phosphorylation have been investigated mainly through two-dimensional
      immunofluorescence (IF). We recently used chromatin immunoprecipitation (ChIP) to
      measure gamma-H2AX densities along chromosomal DNA strands broken in G(1) phase
      mouse lymphocytes. Our experiments revealed that (1) gamma-H2AX densities in
      nucleosomes form at high levels near DSBs and at diminishing levels farther and
      farther away from DNA ends, and (2) ATM regulates H2AX phosphorylation through
      both MDC1-dependent and MDC1-independent means. Neither of these mechanisms were
      discovered by previous if studies due to the inherent limitations of light
      microscopy. Here, we compare data obtained from parallel gamma-H2AX ChIP and
      three-dimensional IF analyses and discuss the impact of our findings upon
      molecular mechanisms that regulate H2AX phosphorylation in chromatin around DNA
      breakage sites.

PMID- 19770595
TI  - Stable knockdown of Aurora-A by vector-based RNA interference in human esophageal
      squamous cell carcinoma cell line inhibits tumor cell proliferation, invasion and
      enhances apoptosis.
AB  - Esophageal squamous cell carcinoma (ESCC) is one of the most malignant cancers,
      and the existing treatment approaches have not been able to effectively manage
      this dreaded cancer. Therefore, continuing efforts are ongoing to explore novel
      targets and strategies for the management of ESCC. It has been shown that
      amplification and overexpression of the Aurora-A occur in several types of human
      tumors, including ESCC. Moreover, overexpression of Aurora-A is shown to
      associate with the grades of tumor differentiation and metastasis of ESCC. These
      render Aurora-A an interesting target for antitumor therapy. Recently, vector
      based RNA interference (RNAi) expression systems have been successfully used to
      silence gene expression, but knockdown of Aurora-A by vector-based RNAi as a
      therapeutic model for ESCC treatment is not fully established. In this study, we
      used a DNA vector-based RNAi approach by expressing short hairpin RNA (shRNA) to
      knockdown Aurora-A. Western blotting analysis and reverse transcription PCR (RT
      PCR) showed that expressions of Aurora-A were efficiently downregulated at both
      the protein and mRNA levels by stable transfection with Aurora-A siRNA expression
      vector. The stable suppression of Aurora-A expression inhibited the proliferation
      and invasion of EC9706 cells. Furthermore, when Aurora-A was stably
      downregulated, cisplatin-induced cytotoxic effects and apoptosis were increased
      dramatically. These data indicate that vector-mediated silencing of the Aurora-A
      gene may provide new avenues toward the study of the role of Aurora-A
      overexpression in tumor cells. Make a novel therapeutic approach to treatment of
      ESCC and other malignant tumors overexpressing Aurora-A.

PMID- 19770594
TI  - Inflammation: a driving force speeds cancer metastasis.
AB  - It has been increasingly recognized that tumor microenvironment plays an
      important role in carcinogenesis. Inflammatory component is present and
      contributes to tumor proliferation, angiogenesis, metastasis and resistance to
      hormonal and chemotherapy. This review highlights the role of inflammation in the
      tumor metastasis. We focus on the function of proinflammatory factors,
      particularly cytokines during tumor metastasis. Understanding of the mechanisms
      by which inflammation contributes to metastasis will lead to innovative approach
      for treating cancer. How tumor spread remains an enigma and has received great
      attention in recent years, as metastasis is the major cause of cancer mortality.
      The complex and highly selective metastatic cascade not only depends on the
      intrinsic properties of tumor cells but also the microenvironment that they
      derive from. An inflammatory milieu consisting of infiltrated immune cells and
      their secretory cytokines, chemokines and growth factors contribute significantly
      to the invasive and metastatic traits of cancer cells. Here, we review new
      insights into the molecular pathways that link inflammation in the tumor
      microenvironment to metastasis.

PMID- 19770596
TI  - Neck/shoulder exercise for neck pain in air force helicopter pilots: a randomized
      controlled trial.
AB  - STUDY DESIGN: The study was a randomized, controlled trial with blinded outcome
      assessment. A 6-week intervention was followed up directly afterwards and after
      12 months. OBJECTIVE: The purpose was to evaluate the preventive efficacy of a
      neck/shoulder exercise regimen for neck pain in air force helicopter pilots.
      SUMMARY OF BACKGROUND DATA: Neck pain is a significant medical problem in modern
      military aviation. Research shows neck-muscle dysfunction in subjects with
      various neck disorders. So far, evidence for neck exercise as prevention or early
      intervention is sparse, and few trials use randomized controlled design. METHODS:
      Sixty-eight helicopter pilots on active flying duty with or without neck pain
      were randomly assigned to a supervised neck/shoulder exercise regimen or a
      control group receiving no such regimen. The key outcome was change in the
      prevalence of neck pain cases at the 12-month follow-up, rated for the previous
      week and the previous 3 months. Secondary outcomes included neck-flexor surface
      electromyographic activity during active craniocervical flexion and pain-related
      fear regarding physical activity. In addition, a secondary regression analysis
      included preintervention predictors that may be associated with change in
      prevalence of neck-pain cases at the 12-month follow-up. RESULTS: Eighty-two
      percent (56/68) of the participants assigned at random completed the intervention
      and provided data at month 12. Regression analysis showed a reduction in the
      prevalence of neck pain cases in the exercise group, which was significant for
      pain ratings during the previous week, OR = 3.2 (95% CI = 1.3-7.8), and previous
      3 months, OR = 1.9 (95% CI = 1.2-3.2). Electromyographic activity at the highest
      contraction level was significantly reduced in the exercise group, P < 0.05,
      whereas no between-groups effect emerged for pain-related fear. Results from the
      secondary analysis showed that general strength training for more than 1 hour per
      week before the intervention predicted reduction in prevalence of pain at follow
      up. CONCLUSION: A supervised neck/shoulder exercise regimen was effective in
      reducing neck pain cases in air force helicopter pilots. This was supported by
      improvement in neck-flexor function postintervention in regimen members. However,
      no effect emerged for pain-related fear. General strength training before the
      intervention predicted reduction in prevalence of pain at follow-up.

PMID- 19770597
TI  - Matrix metalloproteinase-3 on ligamentum flavum in degenerative lumbar
      spondylolisthesis.
AB  - STUDY DESIGN: Human ligamentum flavum (LF) was examined for the activity level of
      matrix metalloproteinase-3 (MMP-3) in degenerative spondylolithesis (DS) patients
      using immunohistochemistry, Western blot, reverse transcriptase-polymerase chain
      reaction (RT-PCR), and quantitative real-time PCR. OBJECTIVE: To investigate the
      hypothesis that the activity of MMP-3 is elevated in LF of DS patients, which
      might contribute to DS pathogenesis. SUMMARY OF BACKGROUND DATA: MMP-3 is a
      proteinase produced by connective tissue cells and is responsible for the
      degradation and modification of extracellular matrix molecules. MMP-3 activity
      has been established in articular cartilage, synovial membrane, and
      intervertebral discs, but not in the LF. METHODS: The experimental group
      consisted of 18 patients with DS and the control group consisted of 18 patients
      with spinal stenosis (SS) without any instabilities. MMP-3 expression was
      measured with in situ using immunohistochemistry and both for mRNA and protein
      levels. RESULTS: The MMP-3 positive cell ratio in the LF observed in DS patients
      was substantially higher than in SS patients (P = 0.030). In Western blot, the
      average optical density (OD) of MMP-3 was higher in LF of DS than of SS (P =
      0.028). There was greater MMP-3 expression in DS patients as quantified by RT-PCR
      (P = 0.004). CONCLUSION: Our study shows that MMP-3 expression in the LF of DS
      patients was significantly higher than in SS patients. Increased MMP-3 expression
      may be associated with the degenerative changes of LF in DS patients comprising
      one of the mechanisms of pathogenesis in DS.

PMID- 19770598
TI  - Relative efficacy of transcranial motor evoked potentials, mechanically-elicited
      electromyography, and evoked EMG to assess nerve root function during sustained
      retraction in a porcine model.
AB  - STUDY DESIGN: This is an animal experiment using transcranial motor evoked
      potentials (TcMEP), mechanically elicited electromyography (EMG), and evoked EMG
      during spinal nerve root retraction in a pig model. OBJECTIVE: To compare the
      sensitivity of these 3 electrophysiological measures for a constant retraction
      force applied to an isolated lumbar nerve root for a specific duration of time.
      SUMMARY OF BACKGROUND DATA: The incidence of nerve root injury during lumbar
      spine surgery ranges from 0.2% to 31%. Direct retraction of spinal nerve roots
      may cause these injuries, but the amount and duration of force that may safely be
      applied is not clear. Using an established porcine model, we examined the changes
      occurring to multimyotomal TcMEPs, mechanically elicited EMGs, and evoked EMGs
      during continuous retraction of a nerve root at a constant force applied over 10
      minutes. METHODS: TcMEP, mechanically elicited EMG, and evoked EMG responses were
      recorded from the tibialis anterior (TA) muscle in 10 experiments. The dominant
      root innervating the TA was determined with evoked EMG; preretraction TcMEP and
      nerve root stimulation threshold (NRT) was obtained. The dominant root was
      retracted at 2 Newton (N) for 10 minutes. TcMEP trials were elicited every minute
      during retraction. NRT was measured immediately after retraction. TcMEP and NRT
      were measured after 10 minutes of recovery. RESULTS.: During the 10 minutes of
      retraction at 2 N, the amplitude of the TA muscle progressively decreased in all
      trials in a highly significant curvilinear fashion. The mean TcMEP amplitude
      decreased 59% +/- 14% from baseline values. The mean NRT after 10 minutes of
      retraction at 2 N rose to 1.8 +/- 0.7 mA (P < 0.01 vs. baseline). The NRT
      increase after retraction strongly correlated with the decrease in motor evoked
      potentials amplitude in the TA (R = 0.90, P < 0.001). EMG activity was variable;
      tonic EMG was observed in only 2 nerve roots (20%). CONCLUSION: Three
      electrophysiologic methods were used intraoperatively to assess neural function
      during retraction of a single nerve root. Retraction produced consistent changes
      in TcMEPs and evoked EMG. These 2 methods show promise for assessing the limits
      on the force and duration of nerve root retraction during spine surgery.
      Mechanically elicited EMG was not sensitive to the amount and duration of nerve
      root retraction.

PMID- 19770599
TI  - Effect of iliac screw insertion depth on the stability and strength of lumbo
      iliac fixation constructs: an anatomical and biomechanical study.
AB  - STUDY DESIGN: Comparison of feasibility and safety of the placement of short and
      long iliac screws by anatomic and biomechanical evaluations as they apply to
      lumbo-iliac fixation construct. OBJECTIVE: To compare the stability of the short
      and long iliac screw fixations for lumbo-iliac reconstruction by anatomic and
      biomechanical evaluations. SUMMARY OF BACKGROUND DATA: Spinopelvic reconstruction
      remains a challenge to spine surgeons. Despite the advent of many fixation
      methods, the use of iliac screws seems most favorable so far. Various lengths of
      iliac screws are applied in surgical treatments; however, no biomechanical
      comparison has been reported based on the screw length. METHODS: For anatomic
      observation, CT scan data of 60 Chinese adults were used to measure the details
      of the iliac spine structures. For biomechanical evaluation, 7 adult human
      cadavers (L3-pelvis) were observed. L4-S1 pedicle screw fixation was performed
      with posterior spinal fixation system. On the basis of the lengths of iliac
      screws, 2 groups were tested (short screw group using 70 mm screws and long screw
      group using 138 mm screws). In this study, short and long iliac screws were
      placed in the same specimen. Biomechanical testing was performed on a material
      testing machine under 800 N compression and 7 Nm torsion loading modes for
      stiffness evaluations. Finally, pullout testing was performed for all the iliac
      screws to measure the maximum pullout force. RESULTS: The length of the line
      between posterior superior iliac spine and anterior inferior iliac spine was
      140.6 +/- 1.1 mm, and the distance between this line and the greater sciatic
      notch was 18.3 +/- 0.8 mm. The length of the line between posterior superior
      iliac spine and the second narrowest point was 67.1 +/- 0.62 mm in men and 70.1
      +/- 1.4 mm in women. Insertion lengths of the short and long iliac screws were 70
      +/- 2 mm and 138 +/- 4 mm, respectively. The lumbo-pelvic reconstruction using
      short and long iliac screws restored 53.3% +/- 13.6% and 57.6% +/- 16.2% of the
      initial stiffness in compression testing respectively. In torsion testing, the
      use of short and long iliac screws harvested 55.1% +/- 11.9% and 62.5% +/- 9.2%
      of the initial stiffness, respectively. No significant difference was detected
      between the 2 reconstructions in terms of compressive and torsional stiffness (P
      > 0.05). However, the maximum pullout strength of long iliac screw group was
      significantly higher than the short screw group (P < 0.05). CONCLUSION: The local
      stability is rather difficult to be restored to the original levels regardless
      the length of iliac screws. Obviously, long iliac screws resisted significantly
      greater axial pullout force. However, under physiologic, torsional, and
      compressive loading conditions, the mechanical stability of lumbo-pelvic fixation
      construct with short iliac screws was comparable with that of the long ones.
      Therefore, the use of short iliac screws, which are only about half the length of
      the long iliac screws, could reduce the implantation risk without significantly
      compromising on the stability of the construct.

PMID- 19770600
TI  - Biomechanical effects of laminoplasty versus laminectomy: stenosis and stability.
AB  - STUDY DESIGN: In vitro human cadaveric study simultaneously quantifying sagittal
      plane flexibility and spinal canal stenosis. OBJECTIVE: To compare biomechanical
      stability and the change in cross-sectional area during flexion and extension
      after laminectomy and open-door laminoplasty. SUMMARY OF BACKGROUND DATA: Spinal
      canal stenosis has been quantified in vitro but has not been quantified in
      studies of laminectomy or laminoplasty. METHODS: Cadaveric specimens were loaded
      in physiologic-range flexion and extension using nonconstraining pure moments
      while recording segmental angles optoelectronically. Custom flexible tubing was
      placed within the spinal canal, and water was continuously pumped through the
      tubing while measuring upstream pressure. Spinal canal cross-sectional area
      correlated to water pressure, allowing continuous monitoring of the smallest
      cross-sectional area of the canal. Specimens were tested (1) normal, (2) after
      modeling stenosis by inserting hemispherical wooden beads in the spinal canal at
      3 levels, (3) after open-door laminoplasty at 5 levels, and (4) after expanding
      laminoplasty to laminectomy. RESULTS: Range of motion (ROM) in the normal,
      stenotic, and laminoplasty conditions did not differ significantly. However,
      laminectomy increased ROM significantly more than other conditions. ROM after
      laminectomy was 13% greater than after laminoplasty. After modeling stenosis, the
      cross-sectional area decreased to 52% +/- 12% of normal. Laminoplasty restored
      the cross-sectional area to 70% +/- 12% of normal whereas laminectomy restored
      cross-sectional area to 101% +/- 4% of normal. Among all conditions, areas
      differed significantly except normal versus laminectomy. CONCLUSION: Laminoplasty
      leaves the spine in a significantly more stable condition than laminectomy.
      However, laminoplasty failed to relieve stenosis completely. In this study,
      stenosis was modeled as about 50% occlusion of the spinal canal. The degree of
      stenosis should be considered in clinical decisions of whether laminectomy or
      laminoplasty is more appropriate.

PMID- 19770601
TI  - Facet orientation and tropism: associations with facet joint osteoarthritis and
      degeneratives.
AB  - STUDY DESIGN: Cross-sectional study. OBJECTIVE: To evaluate the association
      between lumbar spine facet joint orientation, facet joint tropism, and facet
      joint osteoarthritis (OA) and degenerative spondylolisthesis (DS) identified by
      multidetector computed tomography in the community-based Framingham Heart Study.
      SUMMARY OF BACKGROUND DATA: The association between lumbar facet joint OA, DS,
      and facet orientation and tropism remains unclear. METHODS.: This study was an
      ancillary project to the Framingham Heart Study. A sample of 3529 participants of
      the Framingham Heart Study aged 40 to 80 underwent multidetector computed
      tomography imaging to assess aortic calcification. One hundred eighty-eight
      individuals were consecutively enrolled in this ancillary study to assess
      radiographic features associated with low back pain. Facet joint OA was evaluated
      at the L3-L4, L4-L5, and L5-S1 spinal levels, using a 4-grade scale. The
      association between facet joint OA, DS, and facet orientation, and tropism was
      examined using multiple logistic regression models adjusting for age, sex, and
      body mass index. RESULTS: At each spinal level the facet joints with OA were more
      sagittally oriented than those without OA, but the difference was statistically
      significant only at L4-L5 spinal level (P = 0.0007). Facet tropism did not show
      an association with facet joint OA at any spinal level. Facet orientation was
      significantly associated with DS (0.89 [0.84-0.94]), however, facet tropism
      showed no association with DS. CONCLUSIONS: The current study confirms a
      significant association between sagittal orientation and OA of the lumbar facet
      joints at L4-L5 and DS. Facet tropism was not associated with occurrence of facet
      joint OA or DS. Additional, longitudinal studies are needed to understand the
      causal relationship between facet joint morphology and OA.

PMID- 19770602
TI  - Pathological vertebral compression fracture of C3 due to a breast cancer
      metastasis in a male patient.
AB  - STUDY DESIGN: A case of vertebral body fracture due to metastatic breast cancer
      in a male patient and a review of the literature are presented. OBJECTIVE: To
      draw attention to the possible adverse skeletal events in breast cancer patients,
      and the need of a watchful staff within the multidisciplinary team in charge.
      SUMMARY OF BACKGROUND DATA: Breast cancer is a rare condition in men, the
      male/female ratio is 1 of 100 approximately; in both sexes bone metastases are
      the most common. The pathologic fracture by spinal metastases can cause intense
      pain with difficult management. Vertebroplasty has been used successfully to
      treat pain and improve functional status in patients with vertebral compression
      fractures due to metastases. METHODS: A 43-year-old male patient was diagnosed of
      having breast epithelial carcinoma after histologic analysis of a femur fracture.
      Following reconstruction, the patient started rehabilitative treatment. In a
      control visit, he referred sudden cervical pain which was initially treated with
      nonsteroidal anti-inflammatory drugs and rest. The patient was seen in a later
      visit and complained about poor response to analgesia. For this reason, a
      radiologic study was carried out, showing signs of fracture of the third cervical
      vertebral body (C3), and was completed with magnetic resonance imaging where the
      diagnosis of osteolytic metastasis was confirmed. RESULTS: After consulting the
      interventionist radiology team, vertebroplasty was carried out aiming to
      diminishing the pain. There were no postoperative complications and the patient's
      recovery from cervicalgia permitted the nonsteroidal anti-inflammatory drugs
      suspension. Two weeks after the vertebroplasty, the patient resumed his
      rehabilitative treatment without presenting cervical pain or mobility limitation.
      CONCLUSION: Spinal metastases treatment may include combinations of radiotherapy,
      vertebroplasty, and bisphosphonates, which have proved analgesic effect and a
      decrease of bone complications; however, out of these options, only
      vertebroplasty allows rapid stabilization and analgesia.

PMID- 19770604
TI  - The effects of inflammation on glial fibrillary acidic protein expression in
      satellite cells of the dorsal root ganglion.
AB  - STUDY DESIGN: After undergoing L5 hemilaminectomy, chromic gut suture was placed
      onto the DRG and the animals were sacrificed at various time-points. OBJECTIVE:
      The purpose of this study was to identify the effects of inflammation on
      satellite cells (SCs) of the dorsal root ganglion (DRG) by analyzing glial
      fibrillary acidic protein (GFAP) expression in of the DRG at various time points.
      SUMMARY OF BACKGROUND DATA: SCs are neuroglial cells that closely interact with
      nerve cells of the DRG. The role of SC remains unknown GFAP expression increases
      in response to CNS injury. Loss of GFAP has impaired Schwann cell proliferation
      and delayed nerve regeneration after injury. METHODS: Sixty rats underwent a left
      L5 hemilaminectomy. In Group I, a chromic-gut suture was place topically on the
      DRG (n = 30), Group II was the sham surgery group (n = 30). DRGs were harvested
      at 6, 24, 48, 72 hours, and 7 days after surgery. In Group III, 6 control rats
      were killed and their bilateral L5 DRG harvested. The harvested DRG were analyzed
      using light microscopy for SC immunoreactivity, using GFAP, HIS-36, TNF-alpha, IL
      1alpha, IL-1beta, IL-6 monoclonal antibodies. RESULTS: One hundred thirty-two
      DRGs were harvested for analysis. Naive controls and neurons did not express
      GFAP. The SC sheath expressed GFAP as early as 6 hours postchromic gut
      application. In Group I, GFAP expression steadily increased after chromic-gut
      application with 100% of SC soma and SC sheaths being GFAP positive at 7 days.
      The contralateral DRG demonstrated delayed GFAP expression, with 83% of SC soma
      and SC sheaths were GFAP positive at 7 days. In Group II, 89% of sacs expressed
      GFAP by 7 compared to 79% in the contralateral undisturbed DRG. CONCLUSION: Under
      physiologic conditions, the expression of GFAP by SCs is undetectable. As the
      inflammatory process develops, GFAP expression steadily increases with 100% of
      SCs being GFAP immunoreactive 7 days after chromic gut application. These data
      suggest that SCs are the primary source of GFAP in the DRG. We hypothesize that
      SC play an important role in the response to early inflammatory injury.

PMID- 19770605
TI  - Intra-arterial injection in the rat brain: evaluation of steroids used for
      transforaminal epidurals.
AB  - STUDY DESIGN: Prospective in vivo experimental animal model. OBJECTIVES: To
      determine the effect of intra-arterial injection of the steroids commonly used
      for transforaminal epidurals on the central nervous system. And to determine if
      all of the steroids have the same effect. SUMMARY OF BACKGROUND DATA.:
      Transforaminal epidural steroid injection is commonly employed to treat radicular
      pain. This approach is associated with complications, including stroke and death.
      While the mechanism is unknown, the leading hypothesis is that intravascular
      injection of particulate steroids leads to microembolization. METHODS: To
      characterize the nature of steroid induced injury, a rodent model was employed.
      The internal carotid artery was dissected and its branches ligated. The external
      carotid artery was ligated, mobilized, cannulated, and injectate administered.
      Five solutions were tested: Depo-Medrol (N = 11), Depo-Medrol carrier (N = 6),
      Solu-Medrol (N = 6), Decadron (N = 8), and normal saline (N = 7). Drugs, in
      volume of 50 microL, were injected into the ICA via the ECA cannula at 25
      microL/min. The extent of central nervous system injury was evaluated by analysis
      of coronal sections of the brain. RESULTS: Cerebral hemorrhage occurred in test
      subjects with the following frequency: 8 of 11 in the Depo-Medrol group, 7 of 8
      in the Solu-Medrol group, and 3 of 6 in the Depo-Medrol carrier group; no lesions
      were identified in the Decadron or saline groups (P < 0.01). Evan's blue dye
      leakage was detected in the Depo-Medrol and Solu-Medrol groups, but not the
      Decadron or saline groups. CONCLUSION: This study presents the first in vivo
      evaluation of intra-arterial steroid injection. Data demonstrate Depo-Medrol, as
      well as its nonparticulate carrier, and Solu-Medrol can produce significant
      injury to the blood-brain barrier when injected intra-arterially. These results
      demonstrate that injury is produced not only by particulate obstruction of the
      cerebral microvasculature, but also by toxicity of the carrier or steroid
      (methylprednisolone).

PMID- 19770606
TI  - Evidence of enhanced expression of osteopontin in spinal hyperostosis of the twy
      mouse.
AB  - STUDY DESIGN: Gene expression and protein localization of osteopontin (OPN) in
      spinal hyperostosis of the twy mouse by means of in situ hybridization,
      immunohistochemistry, and Northern blot analysis. OBJECTIVE: To verify the
      involvement of OPN in spinal hyperostosis in the twy mouse and elucidate its
      ossification pattern at molecular levels. SUMMARY OF BACKGROUND DATA: OPN is a
      molecule that consistently colocalizes with ectopic calcification in human
      pathologic conditions. The twy mouse, which shows ectopic calcification of the
      spinal ligament resulting in hind limb paralysis, is considered to be a model for
      human ossification of the posterior longitudinal ligament of the spine. METHODS:
      Twenty-eight each of age-matched twy, heterozygote, and wild-type mice were
      killed at 2, 4, 8, 12, and 16 weeks old and subject to histologic and/or
      molecular analyses. Sections were hybridized with RNA probes for OPN and also
      stained with anti-OPN antibodies. Total cellular RNA was extracted from the
      cervicothoracic spine of each genotype at 2- and 16-week-old, and gene expression
      for OPN and COL10A1 was quantified by Northern blot analysis. RESULTS: Enhanced
      expression of OPN mRNA was observed in spinal hyperostotic lesions of the twy
      mouse, specifically in cells of the spinal ligament and chondrogenic cells in the
      outer layer of the anulus fibrosus. These trends were also confirmed by
      immunohistochemical analyses. Northern blot analysis showed that a considerable
      amount of OPN transcripts was detected in all genotypes at 2 weeks old, but the
      robust expression of OPN mRNA was maintained only in twy mice at 16 weeks old.
      COL10A1 transcripts were hardly detected regardless of the genotype at 16 weeks
      old. CONCLUSION: OPN was overexpressed in the hyperostotic spinal lesions of twy
      mice, and the hyperostosis was induced mainly by ectopic ossification of the
      spinal ligament. Because OPN is considered to be an inhibitor of calcification,
      further studies will be necessary to verify whether OPN overexpressed in the twy
      mouse is functional.

PMID- 19770607
TI  - Pediatric and adult three-dimensional cervical spine kinematics: effect of age
      and sex through overall motion.
AB  - STUDY DESIGN: Cross-sectional study. OBJECTIVE: To determine the effect of age
      and sex on the three-dimensional kinematics of the cervical spine. SUMMARY OF
      BACKGROUND DATA: Spine kinematics information has important implications for
      biomechanical model development, anthropomorphic test device development, injury
      prevention, surgical treatment, and safety equipment design. There is a paucity
      of data of this type available for children, and it is unknown whether cervical
      spine kinematics of the pediatric population is different than that of adults.
      The helical axis of motion (HAM) of the spine provides unique information about
      the quantity and quality (coupling etc.) of the measured motion. METHODS: Ninety
      subjects were recruited and divided into 6 groups based on sex and age (young
      children aged 4-10 years, older children aged 11-17 years, adults aged 25+
      years). Subjects actively moved their head in axial rotation, lateral bending,
      and flexion/extension. An optoelectronic motion analysis system recorded the
      position of infrared markers placed on the first thoracic vertebrae (T1) and on
      tight-fitting headgear worn by the subjects. HAM parameters were calculated for
      the head motion with respect to T1. RESULTS: HAM location in axial rotation and
      flexion/extension was more anterior in young females compared to adult females.
      Young females had a more anterior HAM location in flexion/extension compared to
      young males, indicating an effect of sex. For females, the HAM locations of
      adults were superior to those of children in flexion/extension and lateral
      bending whereas in males the HAM locations of adults were inferior to those of
      children. Age-related differences in HAM orientation were also observed in axial
      rotation and lateral bending. CONCLUSION.: Cervical spine kinematics vary with
      age and sex. The variation in spine mechanics based on age and sex found in the
      present study may indicate general trends that would grow stronger in even
      younger children (age <4 years).

PMID- 19770608
TI  - The influence of cervical traction, compression, and spurling test on cervical
      intervertebral foramen size.
AB  - STUDY DESIGN: A comparative measurement design investigating the C4-Th1
      intervertebral foramen under simulated clinical tests for cervical radiculopathy
      using magnetic resonance imaging. OBJECTIVE: The purpose of this study was to
      evaluate functional changes in the cervical intervertebral foramen during the
      axial compression test (ACT), axial distraction test (DT), and Spurling test
      (SST). SUMMARY OF BACKGROUND DATA: Although alterations of the cross-sectional
      area of the cervical intervertebral foramen during flexion/extension and rotation
      have been reported, there are no studies that have measured functional changes in
      foramen cross-sectional area (FCSA) or shape during the simulation of clinical
      tests for cervical radiculopathy. METHODS: 23 participants (12 men, age: 24.52
      years) without history of significant spinal disorders were studied. The 3
      dimensional sequence of the magnetic resonance imaging of the foramen was
      performed with a 0.2-T horizontally open unit. Measurements were taken of FCSA
      and foramen shape (ratio of foramen height to FCSA). These measurements were
      conducted under 4 different conditions; control-resting in supine, DT-neck in
      neutral with a 12 kg distraction force, ACT-neck in neutral with a 7 kg axial
      compression force, SST-the cervical spine was extended (12.79 degrees ), rotated
      (63.36 degrees ), and laterally flexed (28.49 degrees ), in a standardized
      manner. RESULTS: At all levels except for C7-Th1, the FCSA significantly
      increased (P < 0.05) during the DT to around 120% of control. In contrast, FCSA
      significantly decreased to approximately 70% of control (P < 0.05) at all levels
      during the SST. In addition, there were significant differences (P > 0.05) in
      foramen shape between the ACT and SST condition, but only at the C4-C5 and C5-C6
      levels. CONCLUSION: During 3 clinical tests for cervical radiculopathy
      functional, relevant, and changes in the cervical intervertebral foramen were
      evident particularly in the middle cervical spine.

PMID- 19770609
TI  - Empirical evidence of an association between internal validity and effect size in
      randomized controlled trials of low-back pain.
AB  - STUDY DESIGN: We conducted a methodologic study. OBJECTIVE: The objective of this
      study was to assess the validity of the criteria list recommended by the Cochrane
      Back Review Group Editorial Board by evaluating whether individual items and a
      total score are associated with effect sizes in randomized controlled trials of
      back-pain interventions. SUMMARY OF BACKGROUND DATA: There is concern that
      studies of low methodologic quality may exaggerate the effectiveness of
      treatments for low back pain. We performed this study to examine the association
      between a common measure of internal validity and the reported magnitude of
      treatment effects. METHODS: We assessed the relationship between the 11 items
      contained in the Cochrane Back Review Group Internal Validity checklist and
      effect size in randomized trials of interventions for back pain. Of 267 trials in
      15 Cochrane reviews that were eligible for inclusion, 51 were excluded, leaving
      216 trials included in the analysis. The scores on the 11 items for each trial
      were taken from the original review. We extracted effect sizes from each low back
      pain trial. RESULTS: We found that trials that fulfilled a specific item had
      smaller effect sizes compared with trials that did not fulfill that item for 10
      of the 11 items, and for 6 of the criteria, the absolute difference in effect
      sizes was 0.10 or greater. The 95% confidence interval of the difference in
      effect sizes crossed the null value in each case. The number of items fulfilled
      showed that trials with higher scores consistently reported smaller effect sizes
      than trials with lower scores. At the thresholds of 5 or 6 items fulfilled, the
      difference in effect sizes was 0.20 in each case (95% confidence intervals 0.05
      0.35 and 0.06-0.34, respectively). Stratified analyses did not support
      confounding by intervention. CONCLUSION: We conclude that the 11-item Internal
      Validity Checklist is associated with effect size in randomized trials of
      interventions for back pain, and that our data support the use of a sum score of
      the number of fulfilled items in this list.

PMID- 19770610
TI  - Operative versus nonoperative treatment of leg pain in adults with scoliosis: a
      retrospective review of a prospective multicenter database with two-year follow
      up.
AB  - STUDY DESIGN: Retrospective review of a prospective, multicenter study.
      OBJECTIVE: The purpose of this study was to assess the prevalence and severity of
      leg pain in adults with scoliosis and to assess whether surgery significantly
      improved leg pain compared with nonoperative management. SUMMARY OF BACKGROUND
      DATA: Patients with adult scoliosis characteristically present with pain. The
      presence of leg pain is an independent predictor of a patient's choice for
      operative over nonoperative care. METHODS: Data were extracted from a
      prospective, multicenter database for adult spinal deformity. At enrollment and
      follow-up, patients complete the Oswestry Disability Index (ODI) and assessment
      of leg pain using the numerical rating scale (NRS) score, with 0 and 10
      representing no pain and unbearable pain, respectively. Plan for operative or
      nonoperative treatment was made at enrollment. The vast majority of adult
      scoliosis patients seen in our surgical clinics have received nonoperative
      therapies and are being seen for a surgical evaluation. Patients are counseled
      regarding operative and nonoperative management options and are in general
      encouraged to maximize nonoperative treatments. RESULTS: Two hundred eight (64%)
      of 326 adults with scoliosis had leg pain at presentation (mean NRS score = 4.7).
      Ninety-six patients with leg pain (46%) were managed operatively and 112 were
      treated nonoperatively. The operative group had higher baseline mean NRS score
      for leg pain (5.4 vs. 4.1, P < 0.001) and higher mean ODI (41 vs. 30, P < 0.001).
      At 2-year follow-up, nonoperative patients had no significant change in ODI or
      NRS score for leg pain (P = 0.2). In contrast, at 2-year follow-up surgically
      treated patients had significant improvement in mean NRS score for leg pain (5.4
      vs. 2.2, P < 0.001) and ODI (41 vs. 24, P < 0.001). Compared with nonsurgically
      treated patients, at 2-year follow-up operative patients had lower mean NRS score
      for leg pain (2.2 vs. 3.8, P < 0.001) and mean ODI (24 vs. 31, P = 0.005).
      CONCLUSION: Despite having started with significantly greater leg pain and
      disability, surgically treated patients at 2-year follow-up had significantly
      less leg pain and disability than nonoperatively treated patients. Surgical
      treatment has the potential to provide significant improvement of leg pain in
      adults with scoliosis.

PMID- 19770611
TI  - Factors related to progression of thoracolumbar kyphosis in children with
      achondroplasia: a retrospective cohort study of forty-eight children treated in a
      comprehensive orthopaedic center.
AB  - STUDY DESIGN: Retrospective cohort. OBJECTIVE: To assess the period prevalence
      and predisposing factors in thoracolumbar kyphosis progression (TLK). SUMMARY OF
      BACKGROUND DATA: TLK is a common presentation in children with achondroplasia.
      This condition occurs very early in life; it is observed during the first
      attempts to sit, and has multifactorial etiology. Studies are limited on the
      radiologic assessment of the angle of wedging of the deformed vertebra, but none
      to our knowledge on TLK progression in achondroplasia. METHODS: The records of 48
      of 103 children with achondroplasia seen between 1997 and 2005 were examined.
      Developmental motor delay (DMD) and other potential predictors of TLK were
      assessed. The criteria for DMD were a child's inability to sit without support by
      6 months and an inability to walk independently by 15 months. Lateral radiographs
      were examined for the magnitude of TLK, thoracic kyphosis, lumbar lordosis,
      percentage of apical vertebral wedging for the height and width of the vertebra,
      and apical vertebral translation. The association between TLK progression and
      potential predisposing factors were assessed using chi test, Fisher exact, t
      test, and binomial regression model for predictor identification. RESULTS: The
      period prevalence of TLK progression in children with achondroplasia was 35.4%.
      TLK progression was significantly related to DMD, risk ratio = 2.40, 95%
      confidence interval = 1.10 to 5.58, apical vertebral translation (P = 0.01), and
      percentage apical vertebral wedging for height (P = 0.01). After adjustment for
      relevant covariates, the relationship between DMD and TLK progression persisted,
      risk ratio = 2.65, 95% confidence interval, 1.20 to 5.91. CONCLUSION: DMD was
      significantly associated with TLK progression and other radiologic parameters
      namely, initial TLK of >25 degrees , percentage of apical vertebral wedging for
      the height of the vertebra, and apical vertebral translation.

PMID- 19770612
TI  - Pelvic fixation of growing rods: comparison of constructs.
AB  - STUDY DESIGN: Retrospective review. OBJECTIVE: To analyze outcomes and
      complications of growing rods fixed to the pelvis. SUMMARY OF BACKGROUND DATA:
      Growing systems with pelvic foundations are used for neuromuscular/syndromic
      scoliosis. There is little data comparing different constructs. This project
      analyzed the outcomes and complications of this population. METHODS:
      Records/radiographs of 36 patients from the Growing Spine database with growing
      rods anchored in the pelvis were studied. Diagnoses included spinal muscular
      atrophy-6, cerebral palsy-5, myelomeningocele-5, congenital-4, arthrogryposis-1,
      and miscellaneous/syndromic-15. Age at surgery was 6.8 +/- 3 years. Preoperative
      curve was 86 degrees +/- 22 degrees and pelvic obliquity was 27 degrees +/- 11
      degrees . Follow-up was 40 +/- 23 months. Rod breakage rate was compared to that
      of 299 patients not fixed to the pelvis. RESULTS: Iliac screws were used in 20
      patients, iliac rods in 10, S-rods in 3, and sacral fixation in 6. Dual rods were
      used in 30 patients; single in 6. At follow-up, mean Cobb improved to 48 degrees
      +/- 20 degrees and pelvic obliquity improved to 11 degrees +/- 7 degrees . Iliac
      screws achieved significantly better Cobb and pelvic obliquity correction than
      sacral fixation (47% vs. 29%, P = 0.04, 66% vs. 40%, P = 0.001). Pelvic obliquity
      correction exceeded major curve correction (P < 0.001). Total gain in T1-S1
      length was 8.6 +/- 4.3 cm; gain during lengthenings was 4.0 +/- 4.7 cm. Bilateral
      rods provided better correction of both pelvic obliquity (67% vs. 44%, P = 0.006)
      and major curve (47% vs. 25%, P = 0.02) than unilateral rods. Six patients have
      undergone final fusion at mean 3.3 +/- 1.8 years after initial surgery. Five
      patients developed deep infections. There were 6 rod breakages; this rate did not
      differ from constructs not anchored in the pelvis (P = 0.36). There were 5
      breakages of iliac screws and none of other anchors (P = 0.035). CONCLUSION:
      Growing rods can include pelvic fixation to correct pelvic obliquity or obtain
      adequate fixation. Dual iliac fixation provides the best correction. Both iliac
      screws and rods provide satisfactory distal fixation; iliac screws had a higher
      rate of breakage. Growing rods with pelvic fixation are effective in deformity
      correction and achieving growth.

PMID- 19770613
TI  - Growing rods for infantile scoliosis in Marfan syndrome.
AB  - STUDY DESIGN: Retrospective review. OBJECTIVE: To evaluate the effectiveness of a
      new growing rod technique in controlling infantile scoliosis in patients with
      Marfan syndrome. SUMMARY OF BACKGROUND DATA: Infantile scoliosis in patients with
      Marfan syndrome is nearly always progressive and poorly controlled by bracing,
      yet previous studies have shown poor results with first-generation extensible
      spinal rod techniques. METHODS: Ten patients with Marfan syndrome and scoliosis
      developing before 3 years of age were treated with growing rods (3 single, 7
      dual). Mean age at initial surgery was 5.3 years (SD, 2.7 years). Before surgery,
      the mean curve was 77.2 degrees (SD, 15.6 degrees ) and the mean thoracolumbar
      kyphosis was 56 degrees (SD, 21 degrees ). Patients on warfarin sodium were
      lengthened at yearly intervals; others, more frequently. Mean follow-up was 87
      months (SD, 30.5 months). RESULTS: Mean curve correction was 51% (SD, 23%)
      overall, 31% (SD, 23%) for single rods, and 60% (SD, 19%) for dual rods. Mean
      coronal and sagittal imbalance improved from 56 to 18 mm and from 31 to 21 mm,
      respectively. The mean length obtained was 11.5 cm (SD, 3.6 cm) overall and 11.2
      cm (SD, 3.60 cm) for the 5 patients with final fusion. Complications included 2
      rod breakages and 3 intraoperative dural leaks. There was 1 anchor dislodgement
      and no postoperative dural leak. No patient developed clinically noteworthy
      junctional kyphosis. One patient died of unrelated causes 3 months after surgery.
      CONCLUSION: As life expectancy improves for patients with neonatal Marfan
      syndrome, spinal deformity becomes an important issue. Extensible spinal growing
      rods are an effective solution to the problem. Dual rods appear to be more
      corrective than single rods. Substantial spinal length can be obtained to
      minimize trunk disproportion. Growing rods may help prevent large infantile
      curves from becoming severe in Marfan syndrome, allowing definitive spinal fusion
      closer to skeletal maturity.

PMID- 19770614
TI  - Prevalence of degenerative imaging findings in lumbar magnetic resonance imaging
      among young adults.
AB  - STUDY DESIGN: A cross-sectional imaging study of young adults. OBJECTIVE: To
      investigate the prevalence of disc degeneration (DD) and displacement, anular
      tears, and Modic changes in lumbar magnetic resonance imaging (MRI) among young
      adults. SUMMARY OF BACKGROUND DATA: Although low back pain in young adulthood is
      common, the prevalence of spinal MRI findings at this age remains virtually
      unknown. METHODS: The study population was a subcohort of the Northern Finland
      Birth Cohort 1986. Subjects living within 100 km of Oulu (n = 874) were invited
      to participate in lumbar MRI at 20 to 22 years of age (mean: 21.2 years). Degree
      of DD, type of Modic changes, and presence of disc bulges, herniations, high
      intensity zone (HIZ) lesions, and radial tears at all lumbar levels were
      assessed. RESULTS: Three hundred twenty-five women and 233 men (n = 558) attended
      the MR imaging. DD was significantly more frequent in men (54% vs. 42%, P =
      0.005), as was multiple DD (21% vs. 14%, P = 0.036). The prevalences of disc
      bulges and radial tears were 25% and 9.1%, respectively, without gender
      differences. HIZ lesions were more common among women than men (8.6% vs. 4.3%, P
      = 0.046), whereas herniations were significantly more common among men (5.6% vs.
      2.5%, P = 0.047). Only 2 disc extrusions were observed, one in each gender. All
      degenerative disc findings were more common at the L5-S1 level except HIZ
      lesions, which were most likely at L4-L5. The prevalence of the Modic changes was
      1.4%, without gender difference, type I being more common than type II.
      Typically, Modic changes were located adjacent to a DD Grade 4 disc and at the 2
      lowest levels. CONCLUSION: Almost half of young Finnish adult aged 21 years had
      at least one degenerated disc, and a quarter had a bulging disc. Modic changes
      and disc herniations were, however, relatively rare.

PMID- 19770615
TI  - The cultural adaptation, reliability, and validity of neck disability index in
      patients with neck pain: a Turkish version study.
AB  - STUDY DESIGN: The cultural adaptation of Neck Disability Index (NDI), the
      validity and reliability of Turkish version. OBJECTIVE: The aim of this study was
      to conduct a study concerning the cultural adaptation of NDI and investigate the
      validity and reliability of its Turkish version in patients with neck pain.
      SUMMARY OF BACKGROUND DATA: The NDI is a reliable evaluation instrument for
      disability but there is no published Turkish version. METHODS: Eighty-eight
      patients with neck pain for at least 3 months were included in the study. NDI,
      The Neck Pain and Disability Scale, and Visual Analogue Scale (VAS) were
      completed by all subjects. Test-retest reliability was determined by using
      intraclass correlation coefficient and Pearson correlation analysis. For the
      determination of concurrent validity, the relation between NDI and VAS was
      examined by Pearson correlation analysis and for the determination of construct
      validity, the relation between NDI and Neck Pain and Disability Scale was
      investigated. RESULTS: Intraclass correlation coefficient score for test-retest
      reliability was 0.979 (95% confidence interval = 0.968-0.986). For concurrent
      validity, the relation between NDI and VAS was investigated, the r value for test
      and retest was 0.508 and 0.620, respectively (P < 0.0001). For construct
      validity, the relation between NDI and the Turkish version of Neck Pain and
      Disability Scale was investigated, the r value for test and retest was 0.659 (P <
      0.0001) and 0.728 (P < 0.0001), respectively. CONCLUSION: The results suggest
      that the Turkish version of the NDI validated in this study is an easy to
      understand, reliable, and valid instrument for the measurement of the limitation
      of activities of daily living and pain caused by neck disorders in the Turkish
      speaking population.

PMID- 19770616
TI  - The history of the halo skeletal fixator.

PMID- 19770617
TI  - Efficacy and safety of prophylactic large dose of tranexamic acid in spine
      surgery: a prospective, randomized, double-blind, placebo-controlled study. Spine
      2008; 33: 2577-80.

PMID- 19770618
TI  - Re: Comparison of Bryan cervical disc arthroplasty with anterior cervical
      decompression and fusion. Clinical and radiographic results of a randomized,
      controlled clinical trial.

PMID- 19770620
TI  - Increased aldosterone among HIV-infected women with visceral fat accumulation.
AB  - Increased aldosterone has been associated with obesity and the metabolic syndrome
      in non-HIV-infected individuals, but aldosterone has not been investigated among
      HIV-infected patients with increased visceral adipose tissue (VAT). Twenty-four
      hour urine aldosterone was assessed among age and BMI-matched HIV-infected women
      with increased VAT, HIV-infected women without increased VAT and healthy
      controls. Twenty-four hour urine aldosterone was higher in HIV-infected women
      with increased VAT and was associated with SBP, VAT and hemoglobin A1c. Increased
      aldosterone may contribute to the detrimental effects of excess visceral
      adiposity on blood pressure and glucose homeostasis among HIV patients.

PMID- 19770623
TI  - Foreskin surface area and HIV acquisition in Rakai, Uganda (size matters).
AB  - INTRODUCTION: Male circumcision reduces HIV acquisition in men. We assessed
      whether foreskin surface area was associated with HIV acquisition prior to
      circumcision. METHODS: In two randomized trials of male circumcision, the surface
      area of the foreskin was measured after surgery using standardized procedures.
      Nine hundred and sixty-five initially HIV-negative men were enrolled in a
      community cohort who subsequently enrolled in the male circumcision trials,
      provided 3920.8 person-years of observation prior to circumcision. We estimated
      HIV incidence per 100 person-years prior to circumcision, associated with
      foreskin surface area categorized into quartiles. RESULTS: Mean foreskin surface
      area was significantly higher among men who acquired HIV (43.3 cm2, standard
      error 2.1) compared with men who remained uninfected (36.8 cm, standard error
      0.5, P = 0.01). HIV incidence was 0.80/100 person-years (8/994.9 person-years)
      for men with foreskin surface areas in the lowest quartile (< or =26.3 cm2),
      0.92/100 person-years (9/975.3 person-years) with foreskin areas in the second
      quartile (26.4-35.0 cm2), 0.90/100 person-years (8/888.5 person-years) with
      foreskin area in the third quartile (35.2-45.5 cm2) and 2.48/100 person-years
      (23/926.8 person-years) in men with foreskin surfaces areas in the highest
      quartile (>45.6 cm2). Compared with men with foreskin surface areas in the lowest
      quartile, the adjusted incidence rate ratio of HIV acquisition was 2.37 (95%
      confidence interval 1.05-5.31) in men with the largest quartile of foreskin
      surface area. CONCLUSION: The risk of male HIV acquisition is increased among men
      with larger foreskin surface areas.

PMID- 19770622
TI  - Tuberculosis among people with HIV infection in the United Kingdom: opportunities
      for prevention?
AB  - OBJECTIVE: To investigate the incidence of, and risk factors for, tuberculosis
      among HIV clinic attendees in the United Kingdom. DESIGN AND METHODS:
      Observational cohort study of 27 868 individuals in the United Kingdom
      Collaborative HIV Cohort collaboration, 1996-2005. RESULTS: Among individuals not
      taking combination antiretroviral therapy (cART), tuberculosis incidence was
      considerably higher among individuals of black African vs. white or other
      ethnicities {incidence rates 9.9 [95% confidence intervals (CIs) 7.2, 12.6], 2.5
      [95% CI 1.8, 3.0] and 4.4 [95% CI 2.7, 6.0] episodes per 1000 person-years,
      respectively}. Tuberculosis incidence decreased with time after starting cART;
      among black Africans, incidence was consistently higher and remained substantial
      (5.3 per 1000 person-years) at 24 months and longer after starting cART. The
      strongest independent risk factors for tuberculosis after cART start were most
      recent CD4 cell count: adjusted rate ratios (aRR) 10.65 (95% CI 6.11, 18.57),
      3.40 (95% CI 2.05, 5.65), 1.77 (95% CI 1.06, 2.96) and 1.84 (95% CI 1.09, 3.12)
      for individuals with CD4 cell counts less than 50, 50-199, 200-349 and 350-499
      cells/microl, respectively, compared with at least 500 cells/microl; and black
      African vs. white ethnicity [aRR 2.93 (95% CI 1.89, 4.54)]. HIV risk group,
      shorter time on cART, later calendar period and unsuppressed viral load were also
      independently associated with incident tuberculosis. CONCLUSIONS: Tuberculosis
      incidence among people attending UK HIV clinics is substantial, particularly
      among those with non-white ethnicity and low CD4 cell counts, even after starting
      cART. Earlier HIV diagnosis is needed in order to implement interventions to
      prevent tuberculosis; tuberculosis preventive therapy should be considered in
      addition to cART.

PMID- 19770624
TI  - Short-term ezetimibe is well tolerated and effective in combination with statin
      therapy to treat elevated LDL cholesterol in HIV-infected patients.
AB  - BACKGROUND: Ezetimibe inhibits intestinal absorption of cholesterol. METHODS:
      Multicentered double-blind, randomized, placebo-controlled, crossover study to
      determine the short-term safety, efficacy, and tolerability of ezetimibe in
      combination with ongoing statin therapy in HIV-infected adults with elevated low
      density lipoprotein cholesterol (LDL-C). Participants on stable HAART with
      fasting LDL-C at least 130 mg/dl and stable statin were randomized to ezetimibe
      10 mg daily or placebo for 12 weeks followed by 4 weeks of washout and then 12
      weeks with alternative study assignment. Percentage and absolute change in LDL-C
      (primary endpoint), total cholesterol, triglyceride, high-density lipoprotein
      cholesterol (HDL-C), apolipoprotein B, and high sensitivity C-reactive protein
      were compared. Changes in clinical symptoms and safety laboratory measurements
      were assessed. RESULTS: Forty-four participants enrolled: 70% men, median age 49
      years, 43% White/Non-Hispanic, median CD4 cell count 547 cells/microl, and 95%
      HIV RNA less than 50 copies/ml. Median (interquartile range) percentage change in
      LDL-C was -20.8% (-25.4, -10.7) with ezetimibe and -0.7% (-10.3,18.6) with
      placebo; the median within-participant effect of ezetimibe was -14.1% (-33.0, 
      5.0; P < 0.0001). Median difference in absolute LDL-C values between ezetimibe
      and placebo was -32 mg/dl (-58, -6, P < 0.0001). Significant differences in
      within-participant effect of ezetimibe were noted for total cholesterol -18.60% (
      27.22, -11.67, P < 0.001), non-HDL-C -23.18% (-33.14, -14.36, P < 0.0001), and
      apolipoprotein B -8.73% (-18.75, 1.99, P = 0.02). No significant changes seen in
      HDL-C, triglyceride, or high sensitivity C-reactive protein. Ezetimibe was well
      tolerated. Adverse events were similar between phases. CONCLUSION: The present
      short-term study found adding ezetimibe to ongoing statin therapy was well
      tolerated and effective in reducing LDL-C, total cholesterol, non-HDL-C, and
      apolipoprotein B. Adding ezetimibe to statin therapy offers reasonable treatment
      option for HIV-infected patients with elevated LDL-C.

PMID- 19770626
TI  - Treatment of adult rhabdomyosarcoma.
AB  - OBJECTIVES: Rhabdomyosarcoma is an exceedingly rare tumor in adults, and standard
      chemotherapy used for children is much less effective in adults. This study
      examines short-term outcomes using doxorubicin, ifosfamide, and vincristine for
      adult rhabdomyosarcoma. METHODS: Pathology records were searched for adults (age,
      >18) with rhabdomyosarcoma treated at our musculoskeletal tumor center. Treatment
      involved surgical resection, radiation therapy, and chemotherapy with
      doxorubicin, ifosfamide, and vincristine. Eleven met inclusion criteria. Mean age
      was 49 (range: 19-72). Tumors sites included upper extremity (4 patients), lower
      extremity (6), and cervix (1). Subtypes were pleomorphic (7), alveolar (1),
      embryonal (1), and mixed alveolar/embryonal (2). RESULTS: Of the 7 patients with
      nonmetastatic disease, 6 had no evidence of disease posttreatment, but 1 died of
      myelodysplastic syndrome after 51 months. Three patients who received neoadjuvant
      chemotherapy had 100% tumor necrosis. One patient with positive margins scheduled
      for adjuvant chemotherapy had local recurrence and metastasis within 2 weeks and
      died 5 months later. Of the 4 patients with metastatic disease on presentation, 1
      had complete response, 2 had partial response with later progression and death at
      8 and 24 months, and 1 had immediate progression and died at 12 months. Mean
      overall survival was 24 months with 6 of 11 (55%) alive at last follow-up. Mean
      disease-free survival was 17 months for all patients and 23 months for the 7
      patients who had remission of all disease. CONCLUSIONS: When combined with
      surgery and radiation therapy, chemotherapy using doxorubicin, ifosfamide, and
      vincristine yielded 55% overall and 64% disease-free survival at 2 years.

PMID- 19770627
TI  - Patterns of recurrence after curative-intent radiation for oligometastases
      confined to one organ.
AB  - OBJECTIVES: We sought to characterize and describe the patterns of distant
      recurrence in patients with macroscopic oligometastases, limited in number
      (<or=5) and confined to one organ, treated with curative-intent stereotactic body
      radiotherapy (SBRT). METHODS: Seventy-seven patients enrolled on prospective
      studies of SBRT for oligometastases are included in the present analysis. All
      available radiography and records were retrospectively reviewed to determine the
      timing and location of recurrences. RESULTS: New metastases occurred in 73% of
      patients. Among these patients, new metastases developed most frequently in the
      same organ (occurring in 82% of first new metastases after SBRT and 89% of
      cumulative new metastases). Metastases to other organs were common as well
      (occurring cumulatively in 79% of patients). In patients with liver
      oligometastases, common sites of further progression included the liver, other
      abdominal organs, and lungs. In patients with lung oligometastases, common sites
      of further progression included the lungs, thoracic lymph nodes, bones, liver,
      and brain. CONCLUSIONS: Patients receiving SBRT for oligometastases confined to
      one organ are apt to develop new metastases, most frequently occurring in the
      initially involved organ, but also commonly in other organs. A subset of patients
      remains disease free after extended follow-up.

PMID- 19770625
TI  - S9511: a Southwest Oncology Group phase II study of trimetrexate, 5-fluorouracil,
      and leucovorin in unresectable or metastatic adenocarcinoma of the stomach.
AB  - OBJECTIVE: The primary objective of this trial was to evaluate the response rate
      for trimetrexate in conjunction with 5-FU and leucovorin (LV) (= TFL) in the
      treatment of advanced gastric cancer in a phase II, cooperative group setting.
      METHODS: Patients with locally advanced, unresectable, or metastatic
      adenocarcinoma of the stomach received trimetrexate 110 mg/m IV over 60 minutes
      day 1, followed by 5-FU 500 mg/m IV bolus and LV 200 mg/m IV over 60 minutes day
      2, followed by oral LV 15 mg every 6 hours x 7 doses, all weekly for 6 weeks
      followed by 2 weeks of rest, continued until progression. RESULTS:
      Characteristics for 37 eligible patients: median age 63 (range: 23-83);
      male/female: 69% of 31%; performance status 0/1/2 15/20/1. The confirmed response
      rate was 19%, and median overall survival was 6 months. Two patients died as a
      result of therapy, 1 because of infection without significant neutropenia, and 1
      due to perforation of a responding gastric lesion. Seventy-two percent
      experienced grades 3 and 4 toxicity, most commonly diarrhea, fatigue, and
      lymphopenia. CONCLUSIONS: This regimen achieves response rates comparable to
      other 5-FU-based regimens, when used in treatment of incurable gastric cancer.
      Toxicity appears manageable.

PMID- 19770628
TI  - A phase II study of irinotecan with biweekly, low dose leucovorin and bolus and
      continuous infusion 5-fluorouracil (modified FOLFIRI) as first line therapy for
      patients with recurrent or metastatic gastric cancer.
AB  - BACKGROUND: To determine the activity and toxicities of a low-dose leucovorin
      plus 5-fluorouracil (5-FU) regimen, combined with irinotecan and administered
      every 2 weeks (modified FOLFIRI), as a first-line therapy for patients with
      advanced gastric cancer. METHOD: Patients were treated with cycles of 150 mg/m
      irinotecan on day 1 plus 50 mg of LV, followed by a 400 mg/m 5-FU bolus and a 22
      hour continuous infusion of 600 mg/m 5-FU on days 1 and 2. RESULTS: The median
      patient age was 55 years (range, 29-75 years), and 77% (34/44) of the patients
      had a performance status (Eastern Cooperative Oncology Group) of 0 or 1. Of the
      44 patients evaluated for their tumor response, 3 patients (6.8%) and 14 patients
      (31.8%) achieved a complete and partial response, respectively, with an overall
      response rate of 38.6% (95% confidence interval, 23.7%-53.6%). 13 patients
      (29.6%) evidenced a stable disease, and 14 patients (31.8%) progressed during the
      course of the treatment. The median time to progression and overall survival time
      were 4.9 months (range, 0.9-22.8 months) and 10.3 months (range, 1.2-29.0 months)
      from the start of the chemotherapy, respectively. A total of 293 cycles were
      assessed for toxicity. The major hematologic toxicities included grade 1 to 2
      anemia (27.6%), neutropenia (48.8%), and grade 3 to 4 neutropenia (12.6%). There
      were 7 cycles of neutropenic fever. Nonhematological toxicities were observed
      grade 3 vomiting (6.8%), grade 3 diarrhea (4.5%), and grade 3 mucositis (2.3%).
      We noted no treatment-related deaths. CONCLUSIONS: The modified FOLFIRI regimen
      lowering of irinotecan and LV doses-is a safe and feasible regimen as a first
      line therapy for patients with recurrent or metastatic gastric cancer.

PMID- 19770629
TI  - Epstein-Barr virus-positive Hodgkin lymphoma-like earlobe lymphoid infiltrate:
      case report.
AB  - Hodgkin lymphoma (HL) is a malignancy of the lymph system usually occurring on
      the lymph nodes. A 57-year-old Japanese woman presented with the chief complaint
      of an enlarging tumor of the left ear. An excisional biopsy was taken, and
      histological examination showed a mixed infiltration of cells, including Reed
      Sternberg cells and their mononuclear forms against a background of small
      lymphocytes. Reed-Sternberg cells were CD15, CD20, CD30, Ki-67, MUM-1, CD45, EMA,
      and Epstein-Barr virus-encoded small RNA was detected by in situ hybridization.
      We diagnosed this tumor as a skin infiltration with a lymphocyte-rich classical
      HL pattern. Skin involvement of HL is most often a secondary phenomenon
      representing a rare late manifestation of disease dissemination; however, we
      could not detect any evidence of systemic lesion for 6 months after the initial
      presentation. A case of HL only involving the skin was reported by several past
      reports, which termed it primary cutaneous HL. But, it is still controversial
      whether HL initially occurs on the skin because a diagnostic gray zone exists
      between HL, some non-HL entities, and nonneoplastic lymphoid infiltrates.
      Clinical and histological features of this case suggest that the skin will become
      a primary site of HL.

PMID- 19770630
TI  - A dyshidrosis-like variant of adult T-cell leukemia/lymphoma with
      clinicopathological aspects of mycosis fungoides. A case report.
AB  - Adult T-cell leukemia/lymphoma (ATL) is an aggressive type of leukemia/lymphoma
      associated with the human T-cell lymphotropic virus (HTLV-I). We describe an
      adult male patient clinically and pathologically diagnosed as mycosis fungoides
      and treated with chemotherapy after which complete involution of the lesions
      occurred. The disease relapsed with confluent dyshidrosis-like vesicles on the
      palmoplantar regions, followed by disseminated vesiculopapules and associated
      lymphocytosis. A serological test performed at this time revealed HTLV-I
      infection, and a diagnosis of chronic ATL was made. Monoclonal integration of
      HTLV-I was detected in peripheral blood mononuclear cells by inverse long
      polymerase chain reaction. A skin biopsy revealed spongiosis, Pautrier abscesses,
      and intraepidermal vesicles with atypical lymphocytes and an infiltration of
      small and atypical CD4 lymphocytes in the superficial dermis. Proliferative index
      (Ki-67) was 70%. This is the first reported vesicular cutaneous ATL with
      confirmation of HTLV-I proviral integration. The delay that occurred in
      diagnosing ATL was due to the fact that mycosis fungoides and ATL may present the
      same clinical, histopathological, and immunohistochemical features.

PMID- 19770631
TI  - Factor XIIIa+ dermal dendrocyte parasitism in American tegumentary leishmaniasis
      skin lesions.
AB  - Dendritic cells belong to a family of antigen-presenting cells that are localized
      at the entry sites, such as skin and mucosa. Dendritic cells are related to
      immune surveillance function. The role of Langerhans cells in the pathogenesis of
      skin infectious diseases is well studied; however, there are few articles
      addressing involvement of factor XIIIa-positive dermal dendrocytes (FXIIIa+ DD)
      in such processes. FXIIIa+ DDs are bone marrow-monocytic lineage-derived cells
      and members of the skin immune system. Due to their immune phenotype and
      functional characteristics, they are considered complementary cells to Langerhans
      cells in the process of antigen presentation and inducing immune response. To
      verify the interaction between FXIIIa+ DD and Leishmania amastigotes, 22 biopsies
      of American tegumentary leishmaniasis (ATL) skin lesions were subjected to double
      staining technique with anti-factor XIIIa and anti-Leishmania antibodies. FXIIIa+
      DDs were hypertrophic and abundant in the cutaneous reaction of ATL. FXIIIa+ DDs
      harboring parasites were observed in 11 of 22 skin biopsies. The data obtained
      suggest that FXIIIa+ DD plays a role in the pathogenesis of ATL skin lesion as
      host cell, immune effector, and/or antigen-presenting cell.

PMID- 19770633
TI  - Challenge.

PMID- 19770632
TI  - Dermatopathology examination in europe: a summary of 6 years of the European
      Board Certification.

PMID- 19770634
TI  - Anemia management with darbepoetin-alfa in outpatient hemodialysis patients
      switched from epoetin-alfa: a community hospital experience.
AB  - Epoetin-alfa (EA) and darbepoetin-alfa (DA) are agents for treating anemia in
      dialysis patients. In September 2005, our free-standing outpatient hemodialysis
      center (community-hospital based) implemented an interchange from EA to DA. Since
      then, all hemodialysis patients receive DA as the preferred agent. We performed
      this observational study to compare effectiveness of DA with EA in anemia
      management in a cohort of hemodialysis outpatients. We studied 98 hemodialysis
      outpatients who received twice to thrice weekly EA from January to August 2005.
      These patients were switched to DA in September 2005, and baseline DA dose was
      calculated from the conversion table in the package insert. After a 4 month
      titration phase, the same cohort of patients, now on once weekly DA, was followed
      from January to September 2006. Dose of EA or DA was adjusted to maintain
      hemoglobin at 11 to 13 g/dL. Hematologic and dialysis parameters were collected
      on a monthly basis, and inpatient data were excluded. Mean +/- standard deviation
      age was 65.8 +/- 14.2 years, with 42 (42.9%) women. Mean +/- standard deviation
      hemoglobin level was 12.5 +/- 1.6 g/dL during EA and 12.5 +/- 1.6 g/dL during DA
      therapy (P = 0.23). Proportion of patients achieving hemoglobin (11-13 g/dL) was
      44.5% +/- 28.9% with EA and 49.8% +/- 25.8% with DA (P = 0.09). Average
      intrapatient absolute hemoglobin variability was 1.0 +/- 0.5 g/dL on EA and 1.1
      +/- 0.5 g/dL on DA (P = 0.29). Median (and interquartile range) EA dose used was
      11,400 (7,050-22,800) IU/week, and median DA dose was 59.8 (40-91.6) mcg/week
      with an EA:DA dose conversion ratio of 191:1. Patients on EA or DA had similar
      dialysis adequacy, albumin, and iron parameters. DA is as effective as EA in
      treating anemia in hemodialysis outpatients. Dose requirement of DA is greater
      than 200:1 of the amount of EA and may not translate into cost savings.

PMID- 19770636
TI  - Clinical response of large cell neuroendocrine carcinoma of the lung to
      perioperative adjuvant chemotherapy.
AB  - Patients with large cell neuroendocrine carcinoma (LCNEC) of the lung are
      considered to have poor prognosis. However, the benefit of adjuvant chemotherapy
      for these patients has not been established. In this study, we retrospectively
      evaluated the efficacy of perioperative chemotherapy for patients with completely
      resected LCNEC in a single-center setting. From 1999 through 2007, 45 patients
      with surgically resected LCNEC or mixed LCNEC containing at least one portion of
      the neuroendocrine differentiation or morphology in non-small cell lung carcinoma
      were enrolled as participants of this study. Survival rates were calculated by
      the Kaplan-Meier method. Differences between survival curves were computed with
      the log-rank test. For multivariate analysis, the Cox's proportional hazards
      regression model was used to evaluate variables that were significant predictors
      of survival. Of 1397 patients undergoing surgical resection for primary lung
      cancer from 1999 to 2007, 45 (3.2%) were classified as LCNEC. Thirty-six (80%)
      patients were men, and nine (20%) were women. Twenty-four (92%) of 26 patients
      were present or past smokers. Twenty-three (41%) of 45 patients received
      perioperative chemotherapy, including seven induction chemotherapies and 16
      adjuvant chemotherapies. Survival of patients who underwent perioperative
      adjuvant chemotherapy was significantly higher than that of those who received
      surgery alone (P = 0.04). The 5-year survival rate of patients who underwent
      perioperative adjuvant chemotherapy was 87.5%, whereas that of patients who
      underwent surgery alone was 58.5%. Even in stage I cases, perioperative adjuvant
      chemotherapy still favors survival compared with surgery alone. In the Cox
      proportional hazard multivariate analysis, surgery with or without chemotherapy
      showed an independent prognostic influence on overall survival (P = 0.0457).
      Patients who received surgery alone were 9.5 times more likely to die than
      patients who underwent surgery plus chemotherapy. In conclusion, perioperative
      chemotherapy will be needed to improve survival in patients with LCNEC. As the
      population of LCNEC is small, it has been difficult to conduct randomized
      controlled trials to show the survival benefit of adjuvant chemotherapy. This
      should be, therefore, evaluated further in prospective multi-institutional phase
      II trials.

PMID- 19770635
TI  - Erlotinib 150 mg daily plus chemotherapy in advanced pancreatic cancer: an
      interim safety analysis of a multicenter, randomized, cross-over phase III trial
      of the 'Arbeitsgemeinschaft Internistische Onkologie'.
AB  - To date, only limited toxicity data are available for the combination of
      erlotinib with either capecitabine or gemcitabine as front-line therapy for
      advanced pancreatic cancer. Within a randomized phase III trial, 281 treatment
      naive patients were randomly assigned between capecitabine (2000 mg/m/day, for 14
      days, once every 3 weeks) plus erlotinib (150 mg/day, arm A) and gemcitabine
      (1000 mg/m as a 30-min infusion) plus erlotinib (150 mg/day, arm B). In case of
      treatment failure, patients were crossed over to a second-line treatment with the
      comparator cytostatic drug without erlotinib. The primary study endpoint was the
      time to treatment failure of second-line therapy (TTF2). This interim analysis of
      toxicity contains safety data from the first 127 randomized patients. During
      first-line therapy, patients received a median number of three treatment cycles
      (range 0-13) in both the arms. Regarding chemotherapy, a treatment delay was
      observed in 12% of the cycles in arm A and in 22% of the cycles in arm B. Dose
      reductions of the cytostatic drug were performed in 18 and 27% of treatment
      cycles, respectively. Erlotinib dose reductions were performed in 6 and 11% of
      all cycles. Grade 3/4 hematological toxicity was <10% in both the arms; major
      grade 3/4 toxicities in arms A and B were diarrhea (9 vs. 7%), skin rash (4 vs.
      12%), and hand-foot syndrome (7 vs. 0%). No treatment-related death was observed.
      In conclusion, this interim safety analysis suggests that treatment with
      erlotinib 150 mg/day is feasible in combination with capecitabine or gemcitabine.

PMID- 19770637
TI  - UGT1A1 genotyping: a predictor of irinotecan-associated side effects and drug
      efficacy?
AB  - Irinotecan [Camptosar (CPT-11), Pfizer Pharmaceuticals, New York, USA] is one of
      the most effective chemotherapeutic agents in the treatment of metastatic
      colorectal cancer. In vivo, the prodrug CPT-11 is biotransformed by
      carboxylesterase into its active metabolite SN-38. SN-38 is inactivated by
      uridine disphosphate glucuronosyl transferase 1 (UGT1A1) into the inactive
      compound SN-38G, which is excreted with the bile.This review concentrates on a
      critical evaluation of UGT1A1 gene polymorphism as a predictor of toxicity and
      treatment efficacy in patients who received irinotecan for metastatic colorectal
      cancer. Irinotecan is explained with its main toxicities as well as the
      underlying mechanisms. The enzyme UGT1A1 is shown in the context of other
      metabolic pathways and different UGT enzymes involved. We will review in detail
      the controversy of the current literature with regard to the significance of
      identifying patients carrying the homozygous genotype UGT1A1 28. Racial
      differences concerning UGT enzymes have to be considered when discussing a
      pragmatic approach to determine gene polymorphisms as a predictor of treatment
      efficacy and outcome in patients receiving irinotecan-based chemotherapy. Dose
      dependency of toxicity and the clinical relevance of various UGT1 enzymes and
      single nucleotide polymorphisms in different alternative metabolic pathways are
      clarified to put UGT1A1 genotyping in a broad context with additional and
      competing strategies of patient-tailored therapy.

PMID- 19770638
TI  - Postcardiotomy extracorporeal life support in adults: the optimal duration of
      bridging to recovery.
AB  - Extracorporeal life support (ECLS) is a temporary support of postcardiotomy
      cardiogenic shock (PCS). Mortality of postcardiotomy ECLS often results from
      inability to recognize appropriate patients and bridge them to the next therapy
      before complications. A two-gated strategy for the second bridge transferring was
      suggested. From January 2003 to January 2008, 72 patients (mean 60 years)
      received ECLS for PCS. Indicators of cardiac recovery were identified from the
      physiological responses to ECLS. The optimal ECLS duration for myocardial
      recovery was defined as the supporting time of survivors. Forty-one patients
      weaned off ECLS and 29 survived to discharge. The mean duration of ECLS was 130
      hours. Twenty- eight of the 29 survivors weaned off ECLS within 7 days. ECLS >100
      hours and a refractory phenomenon of persistent hypotension (mean arterial
      pressure < 70 mm Hg) with a high adrenergic demand (inotropic equivalent score >
      35) under a sufficient ECLS (flow > 50 ml x kg x min, SvO(2) > 80%) >24 hours
      were independent risk factors of ECLS nonweaning. The benefits of adult
      postcardiotomy ECLS are controversial after a 7-day support. Bridging should be
      considered in suitable patients having ECLS >7 days or showing instabilities
      under an adequate ECLS >24 hours. Continuing ECLS poses a higher risk of
      mortality.

PMID- 19770639
TI  - Intradorsal hippocampal microinjection of lithium reverses morphine-induced
      impairment of memory in mice: interactions with dopamine receptor mechanism(s).
AB  - In this study, the influence of lithium administration on morphine-induced memory
      impairment and possible interactions with dopamine receptor mechanism have been
      investigated. Considering that the dorsal hippocampus is involved in memory,
      lithium and dopamine agents were injected into the CA1 regions of this site
      (intra-CA1). For memory assessment, a one-trial step-down inhibitory avoidance
      task was used in adult male mice. The results showed that posttraining
      subcutaneous administration of morphine (5 mg/kg) decreased the step-down latency
      on the test day, and this effect was reversed by pretest administration of the
      drug, which may be a form of morphine state-dependent learning. Interestingly,
      pretest intra-CA1 microinjection of different doses of lithium (2 and 4
      microg/mouse) reversed memory impairment induced by posttraining morphine (5
      mg/kg, subcutaneously). In contrast, pretest intra-CA1 administration of either
      D1 receptor antagonist SCH23390 (0.01-1 microg/mouse) or D2 receptor antagonist
      sulpiride (5-10 microg/mouse) inhibited the improvement of memory retrieval by
      lithium (4 microg/mouse, intra-CA1). Single pretest administration of SCH23390 or
      sulpiride neither elicited any response, nor reversed morphine-induced amnesia.
      In conclusion, it can be suggested that the dorsal hippocampal dopaminergic
      system is involved in the improving response of lithium on morphine-induced
      amnesia.

PMID- 19770640
TI  - Cardiac fibrosis and diastolic dysfunction after myocardial infarction in
      apolipoprotein E knockout mice.

PMID- 19770641
TI  - Serial changes in circulating M30 antigen, a biomarker of apoptosis, in patients
      with acute coronary syndromes: relationship with the severity of coronary artery
      disease.
AB  - OBJECTIVES: Growing evidence has indicated the potential clinical usefulness of
      measuring different forms of cytokeratin 18 in patient sera (M30 antigen for
      apoptosis and M65 antigen for necrosis) for distinguishing different forms of
      cell death. Preliminary data have reported altered levels of cytokeratin 18
      fragments in patients with acute coronary syndrome (ACS) and ischemic heart
      disease. In this study, serum levels of M30 and M65 were measured in 74 patients
      with ACS [including 17 cases with unstable angina and 57 patients with acute
      myocardial infarction (AMI)], 25 patients with stable angina, and 23 controls.
      METHODS: In patients with ACS, serial measurements of M30 and M65 were obtained,
      and for each patient, the following values were determined: (i) values at
      admission, (ii) values obtained 24 h after symptom onset, and (iii) values
      obtained at 48 h after symptom onset. The severity of coronary atherosclerosis
      was expressed using the Gensini score. RESULTS: On admission, M30 and M65 levels
      in ACS patients were similar to those observed in stable angina patients and
      control participants. In AMI patients, serum levels of M30 peaked at 24 h and
      declined thereafter at 48 h. Notably, serum levels of M30 measured at 24 h
      correlated significantly and positively with the extent of coronary artery
      disease as measured by the Gensini score in AMI patients (r = 0.253, P<0.05).
      CONCLUSION: Serum levels of the apoptotic marker M30 peak at 24 h after AMI and
      reflects the extent of coronary artery disease in this patient group.

PMID- 19770642
TI  - Auditory displays in anesthesiology.
AB  - PURPOSE OF REVIEW: We outline and discuss recent work on auditory displays,
      covering both auditory alarms that indicate technical or physiological threshold
      levels and informative auditory displays that provide a continuous awareness of a
      patient's well being. RECENT FINDINGS: The struggle to make auditory alarms
      informative proceeds with work on two fronts. In one approach, researchers are
      developing and evaluating auditory alarm displays to indicate the source and
      urgency of off-normal states and are relying on the emergence of smart software
      algorithms to reduce the false-positive rate. In a complementary approach, other
      researchers are providing information about the patient's well being in normal as
      well as abnormal states, generalizing the advantages of variable-tone pulse
      oximetry to other systems and other auditory display formats. In either approach,
      a multidisciplinary team is essential in the design and evaluation of auditory
      displays. Because informative auditory displays may subtly change clinical
      practice, there are repercussions for training. SUMMARY: Auditory display in
      anesthesia can extend well beyond auditory alarms to displays that give the
      anesthesiologist a continuous peripheral awareness of patient well being. Much
      more rigorous approaches should be taken to evaluating auditory displays so they
      add information rather than noise.

PMID- 19770643
TI  - Patient monitoring with head-mounted displays.
AB  - PURPOSE OF REVIEW: Head-mounted displays (HMDs) are head-worn display devices
      that project an information display over the wearer's field of view. This article
      reviews a recent program of research that investigates the advantages and
      disadvantages of monitoring with HMDs, and discusses the design considerations
      and implementation issues that must be addressed before HMDs can be clinically
      adopted. RECENT FINDINGS: HMDs let anesthesiologists spend a larger proportion of
      their time in the operating room looking towards the patient and surgical field,
      and a correspondingly smaller proportion of time looking at the standard
      monitors. Anesthesiologists can detect patient events faster with an HMD when
      they are busy performing procedures, but not during normal monitoring. There was
      no evidence of anesthesiologists' performance or monitoring behavior being
      affected by perceptual issues with the HMD, and no evidence that more events were
      missed with the HMD due to inattentional blindness. SUMMARY: Anesthesiologists
      may be able to monitor their patients more effectively when an HMD is used in
      conjunction with existing monitors, but several engineering and implementation
      issues need to be resolved before HMDs can be adopted in practice. Further
      research is needed on the design of information displays for HMDs.

PMID- 19770644
TI  - Anesthesia information management systems.
AB  - PURPOSE OF REVIEW: This review will summarize and comment upon recent
      developments in the evolution and implementation of anesthesia information
      management systems (AIMS) in current practice. RECENT FINDINGS: Availability of
      inexpensive hardware components has greatly reduced costs, and AIMS are now
      widely available as 'off-the-shelf' software systems, yet AIMS are currently in
      use in only a minority of institutions and anesthetic practices. AIMS have
      evolved rapidly from simple automated record-keeping systems to key components of
      modern medical information networks. The databases generated by AIMS are becoming
      the basis for establishing 'best practices' and for comparing patient care
      outcomes. SUMMARY: The searchable, timed, and dated perioperative documentation
      generated by an AIMS appears to be an evolving requirement for contemporary
      anesthetic practice. The obstacles to more widespread AIMS adoption appear to be
      behavioral and financial rather than technical.

PMID- 19770645
TI  - Ethics, continuing medical education, industry, and anesthesia.

PMID- 19770646
TI  - Anesthesia for patients with severe chronic obstructive pulmonary disease.
AB  - PURPOSE OF REVIEW: Patients with chronic obstructive lung disease experience an
      increased risk of perioperative pulmonary complications. This review presents an
      evidence-based approach to perioperative care designed to optimize management.
      RECENT FINDINGS: Recent research has provided guidance regarding intraoperative
      and postoperative administration of oxygen and the selective use of volatile
      agents. The significance of preoperative malnutrition and postoperative epidural
      analgesia on outcomes has also been explored further. The opportunity for
      anesthesiologists to engage in tobacco interventions and the benefits of
      addressing smoking cessation have been studied. SUMMARY: Optimization for surgery
      includes preoperative treatment of reversible airway obstruction and respiratory
      infections, smoking cessation, and possibly nutritional interventions. Meticulous
      intraoperative monitoring combined with a sound understanding of
      pathophysiological mechanisms underlying air trapping will help clinicians strike
      a balance between permissive hypercapnia and adequate ventilation.

PMID- 19770648
TI  - Efficacy of vitamin supplementation in situations with wound healing disorders:
      results from clinical intervention studies.
AB  - PURPOSE OF REVIEW: This review evaluates the efficacy of vitamin supplementations
      for prevention and treatment of pressure ulcer and surgical wounds on the basis
      of recent clinical intervention studies. RECENT FINDINGS: Intervention studies
      show that an energy and protein-rich oral nutritional supplement providing high
      doses of vitamin C and zinc in combination with arginine may prevent the
      development of pressure ulcers. This measure seems to improve the healing of
      pressure ulcer, which is questionable for vitamin C alone. For surgical wounds,
      data from randomized controlled studies are scarce, but results on the use of
      vitamin C in combination with pantothenic acid are promising. SUMMARY:
      Considerable evidence suggests that supplementation of vitamin C together with
      zinc by an oral nutritional supplement rich in energy, protein and arginine may
      be an efficient tool for pressure ulcer healing in contrast to single vitamin C.
      The evidence for prevention of pressure ulcer by such an oral nutritional
      supplement is comparably low. This fits also for single vitamin C supplementation
      in the healing of surgical wounds. Further, well designed and well powered
      studies on the benefit of antioxidant vitamins for wound healing within a diet
      providing adequate energy and protein are necessary.

PMID- 19770647
TI  - Vitamin D and its role in skeletal muscle.
AB  - PURPOSE OF REVIEW: Vitamin D is best known for its role in regulating calcium
      homeostasis and in strengthening bone. However, it has become increasingly clear
      that it also has important beneficial effects beyond the skeleton, including
      muscle. This review summarizes current knowledge about the role of vitamin D in
      skeletal muscle tissue and physical performance. RECENT FINDINGS: Molecular
      mechanisms of vitamin D action in muscle tissue include genomic and nongenomic
      effects via a receptor present in muscle cells. Knockout mouse models of the
      vitamin D receptor provide insight into understanding the direct effects of
      vitamin D on muscle tissue. Vitamin D status is positively associated with
      physical performance and inversely associated with risk of falling. Vitamin D
      supplementation has been shown to improve tests of muscle performance, reduce
      falls, and possibly impact on muscle fiber composition and morphology in vitamin
      D deficient older adults. SUMMARY: Further studies are needed to fully
      characterize the underlying mechanisms of vitamin D action in human muscle
      tissue, to understand how these actions translate into changes in muscle cell
      morphology and improvements in physical performance, and to define the 25
      hydroxyvitamin D level at which to achieve these beneficial effects in muscle.

PMID- 19770649
TI  - Disorders of the growth plate.
AB  - PURPOSE OF REVIEW: To summarize the recent advances in our understanding of the
      majors genes involved in chondrogenesis and their molecular mechanisms. RECENT
      FINDINGS: Disorders of the growth plate and the resulting skeletal dysplasias are
      a consequence of defects in genes involved in various stages of the chondrocyte
      proliferation and differentiation process. Recent identification of disease genes
      has provided insights into the pathophysiology of many skeletal dysplasias.
      SUMMARY: This knowledge enhances our understanding of the physiology and
      pathophysiology of the growth plate. Many skeletal dysplasias can now be
      characterized at the molecular level, allowing clinicians to provide accurate
      molecular diagnoses and counseling. Further research in this area will likely
      provide insights into possible therapeutic options for disorders of the growth
      plate.

PMID- 19770650
TI  - Growth hormone and bone.
AB  - PURPOSE OF REVIEW: Description of recent progress in our understanding of growth
      hormone (GH) effects on bone. RECENT FINDINGS: Growth hormone deficiency is
      associated with low bone mass in children and adults, in addition to its well
      established impact on growth. Although GH and insulin-like growth factor I have
      direct skeletal actions, it is also possible that disordered parathyroid hormone
      secretion or effect may mediate some of the deleterious consequences of GH
      deficiency on bone. The benefits of GH replacement on bone mineral density have
      been demonstrated in many studies, but it remains unclear whether these are
      consistent across patient subgroups. The impact of GH replacement on fracture
      risk has not been definitively established. The positive effects of GH
      administration on growth are well established in childhood-onset growth hormone
      deficiency, as well as in several other pediatric conditions. Data on
      investigational uses of GH are also presented. SUMMARY: GH may have a relevant
      role in bone physiology and several disease states in addition to growth hormone
      deficiency. Although the salutary effects of GH replacement on bone growth and
      bone density are well characterized, additional studies are required to examine
      the impact of GH replacement on fracture risk as well as potential benefits in
      osteoporosis.

PMID- 19770621
TI  - The effect of combined antiretroviral therapy on the overall mortality of HIV
      infected individuals.
AB  - OBJECTIVE: To estimate the effect of combined antiretroviral therapy (cART) on
      mortality among HIV-infected individuals after appropriate adjustment for time
      varying confounding by indication. DESIGN: A collaboration of 12 prospective
      cohort studies from Europe and the United States (the HIV-CAUSAL Collaboration)
      that includes 62 760 HIV-infected, therapy-naive individuals followed for an
      average of 3.3 years. Inverse probability weighting of marginal structural models
      was used to adjust for measured confounding by indication. RESULTS: Two thousand
      and thirty-nine individuals died during the follow-up. The mortality hazard ratio
      was 0.48 (95% confidence interval 0.41-0.57) for cART initiation versus no
      initiation. In analyses stratified by CD4 cell count at baseline, the
      corresponding hazard ratios were 0.29 (0.22-0.37) for less than 100 cells/microl,
      0.33 (0.25-0.44) for 100 to less than 200 cells/microl, 0.38 (0.28-0.52) for 200
      to less than 350 cells/microl, 0.55 (0.41-0.74) for 350 to less than 500
      cells/microl, and 0.77 (0.58-1.01) for 500 cells/microl or more. The estimated
      hazard ratio varied with years since initiation of cART from 0.57 (0.49-0.67) for
      less than 1 year since initiation to 0.21 (0.14-0.31) for 5 years or more (P
      value for trend <0.001). CONCLUSION: We estimated that cART halved the average
      mortality rate in HIV-infected individuals. The mortality reduction was greater
      in those with worse prognosis at the start of follow-up.

PMID- 19770651
TI  - Immunology.

PMID- 19770653
TI  - Dangerous connections: neutrophils and the phagocytic clearance of activated
      platelets.
AB  - PURPOSE OF REVIEW: Platelets and neutrophils co-localize at sites of vessel
      injury, hemorrhage and thrombosis. Moreover, circulating platelets and leukocytes
      interact productively, and the formation of heterotypic aggregates is a feature
      of acute coronary syndromes, systemic inflammatory, neoplastic and autoimmune
      diseases. We have summarized the evidence suggesting a homeostatic function of
      the interaction, culminating in the removal of activated platelets from the
      bloodstream. RECENT FINDINGS: Anionic phospholipids, that is cell surface 'eat
      me' signals exposed both by activated platelets and dying cells, signals such as
      P-selectin (CD62P), specifically expressed by platelets, as well as of polarized
      clusters of neutrophils beta2 integrins play a role in the capture of platelets
      in vitro and in vivo. SUMMARY: A bona-fide synapse assembles as a consequence of
      the interaction between P-selectin and its counter-receptor on neutrophils, with
      clustering of activated beta2 integrins into membrane microdomains and
      reorganization of cytoskeleton components that control cell motility and
      phagocytosis. Actual engulfment of the tethered platelet depends on the
      recognition of phosphatidylserine and/or of phosphatidylserine-associated
      molecules. This event may have a physiologic role in the regulation of the
      hemostatic potential of circulating blood; conversely, a failure may contribute
      to persistent vascular inflammation and thrombosis.

PMID- 19770654
TI  - Monocytes: subsets, origins, fates and functions.
AB  - PURPOSE OF REVIEW: The term mono-cyte suggests this population of cells consists
      of a single homogenous fraction. However, evidence from a number of laboratories
      indicates that monocytes are composed of several subsets, which differ in
      phenotype, size, nuclear morphology, granularity and gene profiles. Most
      importantly, recent data suggest that monocyte subsets are also functionally
      distinct. Here we summarize the recent advances in our understanding of monocyte
      subsets and their origins, fates and functions. RECENT FINDINGS: The recent past
      has seen major progress in our understanding of myeloid differentiation.
      Specifically, the published literature now suggests a dichotomy that starts at
      the stage of a novel clonotypic bone marrow resident precursor, the macrophage
      dendritic cell progenitor (MDP). Insights into differential origins of
      macrophages and dendritic cells, linked with functional specifications, are
      likely to significantly change our current view of the mononuclear phagocyte
      system. SUMMARY: Contemporary studies have demonstrated that two subsets of
      monocytes reside in the peripheral circulation. These subsets are surprisingly
      distinct; with regard to their functions and fates, for example, one subset might
      be dedicated to generate macrophages upon extravasation from the peripheral
      circulation, whereas, the other subset under inflammatory conditions may
      differentiate into inflammatory dendritic cells. The tissue response during
      pathogenesis seems to differentially mobilize these cells, thereby manipulating
      the local mononuclear phagocyte composition according to acute needs.

PMID- 19770655
TI  - Cardiorespiratory fitness and metabolic risk factors in obesity.
AB  - PURPOSE OF REVIEW: An increase in cardiorespiratory fitness (CRF) through
      exercise training appears to partly ameliorate the health hazards of obesity and
      a number of mechanisms might explain the potential benefits. We review recent
      evidence about the relationships between CRF, exercise training and metabolic
      risk factors in obesity. RECENT FINDINGS: Epidemiological data have shown that
      the anti-inflammatory effects of exercise could be an important mechanism in
      explaining cardio-protective effects of physical activity. Emerging evidence
      suggests that exercise training reduces markers of inflammation and improves
      glucose control in obesity, independent of weight loss. Novel mechanisms appear
      to involve exercise-induced changes in CD14+CD16+ cell populations, expression of
      toll-like receptors, and key changes in the metabolic regulation of visceral
      white adipose tissue. Other promising recent research has focused on exercise
      induced signalling pathways governing glucose metabolism, such as insulin
      receptor substrate and Akt substrate. Using novel imaging techniques, studies
      have demonstrated exercise-induced improvements in lipoprotein subfraction
      particle size, and reduction in visceral adipose tissue and liver fat,
      independent of weight loss. These effects appear to be mostly restricted to
      interventions consisting of relatively high doses of exercise or exercise
      combined with calorie restriction, although further work is required to elucidate
      the dose-response relationships. SUMMARY: Physical activity and the pursuit of
      physical fitness are important in the treatment of obesity because exercise
      training can improve a number of metabolic risk factors independent of weight
      loss. Thus exercise can provide important health benefits irrespective of weight
      loss in obese and overweight individuals.

PMID- 19770656
TI  - Severe hypertriglyceridemia and pancreatitis: presentation and management.
AB  - PURPOSE OF REVIEW: Hypertriglyceridemia (HTG) is a well recognized cause of acute
      pancreatitis accounting for approximately up to 10% of all cases and even up to
      50% of all cases in pregnancy. Both primary and secondary disorders of
      lipoprotein metabolism may be associated with hypertriglyceridemic pancreatitis
      (HTGP). The purpose of this review is to provide an overview of the current
      studies on presentation and management of HTGP. RECENT FINDINGS/CONCLUSION:
      Hydrolysis of triglycerides by pancreatic lipase and formation of free fatty
      acids that induce inflammatory changes are postulated to account for the
      development of HTGP, yet the exact pathophysiology remains unclear. The clinical
      features of patients with HTGP are generally not different from patients with
      acute pancreatitis of other causes, and there is some evidence that HTGP is
      associated with a higher severity or a higher complication rate. There is no
      clear evidence as to which HTG patients will develop pancreatitis. Several
      studies have evaluated the effect of apheresis, the benefit of insulin and/or
      heparin treatment and the use of different antihyperlipidemic agents in HTGP.
      Dietary modifications resemble the key features in the long-term management of
      HTG. Whether HTG may cause chronic pancreatitis in the long-term follow-up
      remains controversial.

PMID- 19770652
TI  - The intestinal microbiota in health and disease: the influence of microbial
      products on immune cell homeostasis.
AB  - PURPOSE OF REVIEW: A vast and diverse array of microbes colonizes the mammalian
      gastrointestinal tract. These microorganisms are integral in shaping the
      development and function of the immune system. Metagenomic sequencing analysis
      has revealed alterations in intestinal microbiota in patients suffering from
      chronic inflammatory diseases, including inflammatory bowel disease and asthma.
      This review will discuss the mechanisms through which the innate immune system
      recognizes and responds to the intestinal microbiota as well as the effect of
      specific microbiota-derived signals on immune cell homeostasis. RECENT FINDINGS:
      Recent studies in murine model systems have demonstrated that manipulation of the
      intestinal microbiota can alter mammalian immune cell homeostasis. Specific
      microbial signals have been identified that can impact immune cell function both
      within the intestinal tract and in peripheral tissues. These microbiota-derived
      signals can either have an immunoregulatory effect, creating an immune state that
      is refractory to inflammation, or conversely, act as an adjuvant, aiding in the
      propagation of an immune response. SUMMARY: Associations between alterations in
      the microbiota and human disease implicate intestinal microbial signals in
      shaping immune responses. These signals are recognized by innate immune cells and
      influence the ability of these cells to modulate both the local and systemic
      immune response.

PMID- 19770657
TI  - Classification and management of anaplastic gliomas.
AB  - PURPOSE OF REVIEW: To summarize findings, discuss problems and define new
      questions from the past phase III trials in anaplastic gliomas. RECENT FINDINGS:
      The current standard of care for first-line treatment in anaplastic gliomas is
      radiotherapy or chemotherapy. The next steps are to define the role and optimal
      sequencing of combined modality treatment focusing on radiotherapy and
      temozolomide and to develop trials with novel targeted treatments. The feature of
      necrosis in oligodendroglial tumors needs to be further studied, and molecular
      prognosticators will take more room. These include O6
      methylguanylmethyltransferase promoter methylation, isocitrate dehydrogenase
      mutations and epidermal growth factor receptor amplification. Further, the notion
      that all anaplastic oligodendroglial tumors with or without a relevant astrocytic
      component fall into the same prognostic category and the obvious difficulties to
      type and to grade anaplastic gliomas pose an enormous burden on local diagnosis.
      The current and upcoming trials including the European Organization for Research
      and Treatment of Cancer 26053/22054 trial aim at solving some of these issues
      with an initial central pathology review. SUMMARY: Anaplastic gliomas are an
      important group of brain tumors to develop future molecularly targeted therapies
      and should therefore be in the main focus of academic and industrial drug
      development, which aims at efficacy and avoiding long-term side effects.

PMID- 19770658
TI  - Treatment of recurrent high-grade gliomas.
AB  - PURPOSE OF REVIEW: Although therapies for patients with recurrent high-grade
      gliomas are limited, there has been important progress recently. This review
      summarizes current treatments for recurrent high-grade gliomas with an emphasis
      on more novel approaches. RECENT FINDINGS: There is increasing evidence that
      antiangiogenic therapies have activity in high-grade gliomas. Recently, the
      United States Food and Drug Administration granted accelerated approval of
      bevacizumab, a humanized monoclonal antibody against vascular endothelial growth
      factor, for the treatment of recurrent glioblastomas. Bevacizumab decreases
      corticosteroid requirements and improves radiologic response rates and
      progression-free survival. The extent to which these agents prolong overall
      survival remains to be determined. There is also emerging evidence that other
      therapies such as dose-dense and metronomic temozolomide regimens, targeted
      molecular agents, and other antiangiogenic therapies may have activity in
      recurrent high-grade gliomas. SUMMARY: Although there has been progress in
      treating recurrent high-grade gliomas, the prognosis remains poor and much work
      still needs to be done to improve on the current results of antiangiogenic and
      targeted molecular therapies, as well as other novel therapies.

PMID- 19770659
TI  - Clinical and immunological features of drug-induced and infection-induced
      proteinase 3-antineutrophil cytoplasmic antibodies and myeloperoxidase
      antineutrophil cytoplasmic antibodies and vasculitis.
AB  - PURPOSE OF REVIEW: Drugs and infections may induce antineutrophil cytoplasmic
      antibodies (ANCA) and vasculitic manifestations mimicking ANCA-associated
      vasculitides (AAV) and mechanisms relevant in their pathogenesis. This review
      summarizes the most recent findings in this field. RECENT FINDINGS: Drug-induced
      and infection-induced proteinase 3 (PR3)-ANCA and myeloperoxidase (MPO)-ANCA may
      be associated with a vasculitis clinically resembling AAV. Mechanisms relevant
      for the break of tolerance and induction of ANCA (e.g. danger signals,
      superantigens, neutrophil extracellular traps, protease-activated receptor-2, IL
      17 cells) may be shared to some extent between drug-induced and infection-induced
      ANCA-positive vasculitis and AAV, especially with regard to the potential role of
      infection in Wegener's granulomatosis. Differences in immunopathology, clinical
      presentation, and functional aspects of ANCA help to distinguish drug-induced and
      infection-induced ANCA-positive vasculitis from AAV, and present new avenues for
      future research in this field. SUMMARY: Medications and infections, which induce
      PR3-ANCA and MPO-ANCA, have to be considered in the differential diagnosis of
      primary AAV. Moreover, there is clinical and experimental evidence for an
      association between certain drugs and infections with ANCA-production. Analysis
      of ANCA-induction in such conditions also sheds new light on our understanding of
      immune mechanisms relevant in the break of tolerance and ANCA-production in AAV.

PMID- 19770660
TI  - Recent advances to achieve remission induction in antineutrophil cytoplasmic
      antibody-associated vasculitis.
AB  - PURPOSE OF REVIEW: Significant advances in the treatment of antineutrophil
      cytoplasmic antibody-associated vasculitis have been made in the past 10 years.
      This review aims to detail advances in treatment aimed at induction of remission.
      RECENT FINDINGS: Cyclophosphamide-based regimes remain the standard of care, at
      least in generalized disease. Safer therapeutic regimes with reduced cumulative
      dose of cyclophosphamide have been developed such as the use of pulsed
      cyclophosphamide. Preliminary data are available, suggesting rituximab may be an
      alternative to cyclophosphamide, but additional safety data are required.
      Evidence suggests that plasma exchange should be added to those with more severe
      disease and it is acceptable to use methotrexate as an induction agent for those
      with limited or early systemic disease. Using current regimens, remission is
      achieved in over 90% of patients, but toxicity remains an important issue.
      Attention should be paid to reducing treatment toxicity. SUMMARY: Findings of
      recent clinical trials should change clinical practice and improve outcome of
      patients with antineutrophil cytoplasmic antibody-associated vasculitis.

PMID- 19770661
TI  - Apparent perioperative hypotension: an unusual presentation of Takayasu's
      arteritis.

PMID- 19770662
TI  - Retrograde autologous priming of the cardiopulmonary bypass circuit reduces blood
      transfusion in small adults: a prospective, randomized trial.
AB  - BACKGROUND AND OBJECTIVE: Extreme haemodilution occurring with cardiopulmonary
      bypass imposes a primary risk factor for blood transfusion in small adult cardiac
      surgical patients. Priming of the cardiopulmonary bypass circuit with patients'
      own blood [retrograde autologous priming (RAP)] is a technique used to limit
      haemodilution and reduce transfusion requirements. We designed this study to
      evaluate the effects of RAP on reducing perioperative blood transfusion in small
      adults. METHODS: One hundred and twenty patients with a body surface area of less
      than 1.5 m undergoing first-time, nonemergency cardiac surgery were randomized to
      either the standard priming group or the RAP group. All patients followed strict
      transfusion criteria. Homologous transfusion, haematocrit, plasma colloid osmotic
      pressure and postoperative clinical outcomes were evaluated perioperatively.
      RESULTS: Patient characteristics and operative parameters were equal for patients
      in both groups. With autologous priming, a mean volume of 614.8 +/- 138.8 ml of
      priming solution was replaced with autologous blood. This allowed a significantly
      higher haematocrit value during cardiopulmonary bypass (P < 0.05). Red blood cell
      transfusion was necessary in 83.3% of patients of the standard priming group on
      pump, whereas only 26.7% of patients of the RAP group required transfusion (P <
      0.01). The overall transfusion rate of the RAP group was significantly less than
      that in the standard priming group during the hospitalization (90.0 vs. 50.0%, P
      < 0.01). Amongst patients who received transfusion on pump, the number of
      homologous units of packed red blood cells was less in the RAP group than that in
      the standard priming group intraoperatively and perioperatively (0.94 +/- 0.32
      vs. 1.48 +/- 0.68 units, P = 0.03; 1.24 +/- 0.54 vs. 1.69 +/- 0.69 units, P =
      0.15). Ten minutes after aortic cross-clamp, colloid osmotic pressure was reduced
      by 39.7 +/- 2.8% in the standard priming group and by 28.6 +/- 3.2% in the RAP
      group (P < 0.05). Clinical outcomes were similar with respect to pulmonary, renal
      and hepatic function, length of ICU stay and hospital stay. CONCLUSION: RAP
      resulted in a significant decrease in intraoperative haemodilution and conserved
      the use of blood. This technique should be considered for patients with a small
      body surface area (<1.5 m) undergoing open heart surgery.

PMID- 19770663
TI  - Current nitrous oxide use in general anaesthesia: an electronic survey.

PMID- 19770664
TI  - Association of physicians' accuracy in recording with quality of care in
      cardiovascular medicine.
AB  - BACKGROUND: Physicians' adherence to cardiovascular (CV) guidelines has been
      found to be poor. In this regard, accuracy in keeping medical records could play
      an important role. This study was devised to describe which data are present in
      medical records from a large sample of physicians and to investigate the
      association and the link between completeness in recording and clinical
      appropriateness. METHODS: The data extracted from medical records of 1078 doctors
      (general practitioners, cardiologists, and diabetologists) were analyzed, with a
      focus on CV prevention. The percentage of recorded data of several CV clinical
      variables was calculated. A multivariate analysis was performed to investigate
      the association between doctors' and patients' characteristics and different
      patterns in recording. Finally, the completeness in recording was calculated with
      a score and plotted against three indicators of appropriateness. RESULTS: The
      only risk factor that achieved a good standard of registration was blood pressure
      (89%). Low-density lipoprotein and waist circumference were largely under
      recorded, whereas lifestyle data collection was almost negligible. Age,
      specialization, and use of electronic records increase the accuracy in recording.
      When one CV risk factor was predominant, the probability of having other risk
      factors recorded was reduced. A significant increase in the proportion of
      patients treated according to guidelines was found in doctors who were more
      accurate in recording. CONCLUSION: A link exists between accuracy in recording
      with both quality of care and adherence to guidelines. Specific training of all
      doctors in this field should be considered.

PMID- 19770665
TI  - Assessment of CPR-D skills of nursing students in two institutions: reality
      versus recommendations in the guidelines.
AB  - Significant differences in basic life support skills including cardiopulmonary
      resuscitation and defibrillation (CPR-D) were detected when nurses working in one
      Finnish and one Swedish hospital were tested using an Objective Structured
      Clinical Examination (OSCE). The purpose of this study was to use OSCE test in
      assessing guideline based CPR-D skills of newly qualified nurses. The CPR-D
      skills of newly qualified registered nurses studying in Halmstad University (n =
      30), Sweden, Helsinki Metropolia University of Applied Sciences (n = 30), and
      Finland were assessed using an OSCE which was built up with a case of cardiac
      arrest with ventricular fibrillation as the initial rhythm. The Angoff average,
      32.47, was calculated as cutoff point to pass the test. Forty-seven percent of
      the students in the Swedish group (mean score 32.47/49, range 26-39, SD 3.76) and
      13% of the students in the Finnish group (mean score 23.80/49, range 13-35, SD
      4.32) passed the OSCE (P<0.0001), the cutoff point being 32.47. Performance grade
      for the Swedish group was 2.9/5.0 and for the Finnish group 2.1/5.0 (P<0.0001).
      Good nontechnical skills correlated with high grading of the clinical skills. In
      conclusion, CPR-D skills of the newly qualified nurses in both the institutes
      were clearly under par and were not adequate according to the resuscitation
      guidelines. Current style of teaching is unlikely to result in students being
      able to perform adequate CPR-D. Standardized testing would help in controlling
      the quality of learning.

PMID- 19770666
TI  - Pancreatic islet cell carcinoma presenting with concurrent Cushing's and
      Zollinger-Ellison syndromes: case series and literature review.
AB  - Cushing's syndrome and Zollinger-Ellison syndrome occur occasionally as a result
      of neuroendocrine cancers. The concurrence of the two syndromes has been
      considered to confer a poor clinical and therapeutic outcome. In this study, we
      are reviewing two patients with pancreatic islet cell carcinomas and with both
      Zollinger-Ellison and Cushing's syndromes, one followed up for more than 5 years,
      and the other still receiving therapy, 5 years since diagnosis. A literature
      review showed that surgery has limited utility as the majority of these patients
      had metastases at the time of diagnosis. Proton-pump inhibitors, ketoconazole,
      and somatostatin antagonists have a major role in controlling symptoms.
      Interferon and systemic chemotherapeutic agents play a role in the management of
      metastatic and fast-growing cases. Chemoembolization and bland embolization show
      encouraging results in controlling liver metastases. The latter was used
      effectively and more than once in the two patients presented herein. On the basis
      of recent molecular genetics studies, target therapy may be helpful, however,
      ongoing trials will define it's utility. As the data confers a worse prognosis
      versus other pancreatic neuroendocrine tumors, the relatively favorable outcome
      of the two patients reported herein may reflect the impact of multiple
      therapeutic modalities.

PMID- 19770667
TI  - Effect of cardiorespiratory training on aerobic fitness and carryover to activity
      in children with cerebral palsy: a systematic review.
AB  - The question under consideration was does cardiorespiratory training improve
      aerobic fitness in children with cerebral palsy and is there any carryover into
      activity? The study design consisted of a systematic review of randomized trials
      using the Cochrane Collaboration guidelines. Participants were children of school
      age with cerebral palsy. Intervention included cardiorespiratory training
      consisting of activities conducted for an extended period, which were progressed
      in terms of duration and/or intensity over time. Combination programs were
      included if cardiorespiratory training comprised at least half of the program.
      Outcomes had to include a measure of aerobic fitness, for example, peak oxygen
      uptake. In addition, measures of activity that reflect aerobic fitness, for
      example, 6-min Walk Test were also desirable. Three studies were identified which
      randomized participants to cardiorespiratory training or no intervention in
      addition to usual physiotherapy. A meta-analysis was not performed because of
      lack of data. Therefore, the between-group differences are reported in terms of
      percentage benefit. Short-term cardiorespiratory training (i.e. 2-4 months)
      increased aerobic fitness by 18-22% and long-term training (i.e. 8-9 months) by
      26-41% compared with no additional intervention. Short-term training (i.e. 2-4
      months) increased activity by 0-13%, and long-term training (i.e. 8-9 months) by
      2-9%. The conclusion is that there is limited evidence about the effect of
      cardiorespiratory training in children with cerebral palsy. The available
      evidence suggests that training may improve aerobic fitness, but that there is
      little carryover into activity.

PMID- 19770668
TI  - The relevance of depressive symptoms and social support to disability in women
      with multiple sclerosis or fibromyalgia.
AB  - Multiple sclerosis and fibromyalgia syndrome may spur substantial disability for
      those affected. Using structural equation modeling, this secondary analysis
      examined predictors of disability in women with multiple sclerosis (n = 118) and
      fibromyalgia syndrome (n = 197) recruited for separate wellness studies. Greater
      functional limitations, lower economic adequacy, less social support, and higher
      depressive symptoms predicted greater disability in both groups. The final
      multigroup model showed good fit chi [(111, n = 315) = 135.92, comparative fit
      index = 0.99, root mean square error of approximation = 0.03] and identified
      similarities and differences across groups.

PMID- 19770669
TI  - Pleiotropic effects with equivalent low-density lipoprotein cholesterol
      reduction: comparative study between simvastatin and simvastatin/ezetimibe
      coadministration.
AB  - BACKGROUND: Coadministration of any statin with ezetimibe is as effective as
      using high doses of the same statin in the reduction of low-density lipoprotein
      cholesterol (LDL-c). There may be other effects called pleiotropics. OBJECTIVE:
      To compare the effectiveness of 2 different treatments that obtain equivalent LDL
      c reductions (80 mg of simvastatin, once a day and coadministration of 10 mg of
      simvastatin and 10 mg of ezetimibe, once a day) over endothelial function and
      inflammation. METHODS: Twenty-three randomized patients with hypercholesterolemia
      in a 2 x 2 crossover protocol were studied. Endothelial function was analyzed by
      ultrasound assessment of endothelial dependent flow-mediated vasodilation of the
      brachial artery, and inflammation was estimated by high-sensitivity C-reactive
      protein (hs-CRP). RESULTS: LDL-c reduction was similar between the 2 treatments
      with simvastatin/ezetimibe and with simvastatin (P < 0.001); no difference
      between treatments was found (P = 0.968). Both treatments improved significantly
      the endothelial function [3.61% with simvastatin/ezetimibe (P = 0.003) and 5.08%
      with simvastatin (P < 0.001)]; no difference was found between the 2 treatments
      (P = 0.291). hs-CRP had a 23% reduction with simvastatin/ezetimibe (P = 0.004)
      and a 30% reduction with simvastatin alone (P = 0.01), with no significant
      difference between the 2 treatments (P = 0.380). CONCLUSION: The 2 forms of
      treatment presented similar pleiotropic effects: improvement in endothelial
      function and decrease in hs-CRP levels.

PMID- 19770670
TI  - Clobutinol delays ventricular repolarization in the guinea pig heart: comparison
      with cardiac effects of HERG K+ channel inhibitor E-4031.
AB  - Clobutinol has been clinically reported to induce long QT syndrome. To clarify
      its cardiac electrophysiological properties, we compared effects of clobutinol on
      the isolated myocardium and anesthetized guinea pig heart with those of a hERG K
      channel blocker, E-4031. In isolated guinea pig ventricular tissues, clobutinol
      (3 microM) as well as E-4031 (10-100 nM) prolonged the action potential duration
      without affecting maximum upstroke velocity, but no further prolongation was
      observed after application of 30 microM clobutinol. In anesthetized closed-chest
      guinea pigs, clobutinol (1 and 10 mg/kg, intravenously) and E-4031 (0.01 and 1
      mg/kg, intravenously) prolonged the QT interval and duration of the monophasic
      action potential (MAP) in a dose-dependent manner and at the same time increased
      the beat-to-beat variability of the MAP duration and reversed use-dependent
      prolongation of the MAP duration and triangulation of the MAP configuration.
      These results suggest that clobutinol delayed the ventricular repolarization and
      increased the proarrhythmic parameters linked to the hERG K channel inhibitor
      induced torsade de pointes arrhythmias.

PMID- 19770671
TI  - Cardiovascular effects of torcetrapib in conscious and pentobarbital-anesthetized
      dogs.
AB  - Torcetrapib is a cholesteryl ester transfer protein inhibitor with an undesired
      response of increasing arterial pressure in humans. Pressor responses to
      torcetrapib have been demonstrated in multiple preclinical species. However,
      these studies have not related plasma concentrations to observed effects. Our
      purpose was to 1) characterize the cardiovascular responses of torcetrapib in
      conscious and anesthetized dogs with measured plasma concentrations; and 2)
      characterize the hemodynamic effects contributing to hypertension using
      comprehensively instrumented anesthetized dogs. Torcetrapib was dosed orally (3,
      30 mg/kg) and intravenously (0.01, 0.33, 0.1 mg/kg) in conscious and anesthetized
      dogs, respectively. Mean arterial pressure and heart rate were monitored in both
      models; additional parameters were measured in anesthetized dogs. Plasma drug
      concentrations were assessed in both models. In conscious and anesthetized dogs,
      torcetrapib increased mean arterial pressure 25 and 18 mm Hg and heart rate 35
      and 21 beats/min, at 2.94 and 3.99 microg/mL, respectively. In anesthetized dogs,
      torcetrapib increased pulmonary arterial pressure, both systemic and pulmonary
      hypertension driven by increases in vascular resistance. The compound increased
      rate pressure product and myocardial contractility while decreasing time to
      systolic pressure recovery and ejection time. Thus, torcetrapib-induced pressor
      responses are mediated by systemic and pulmonary vasoconstriction and are
      associated with increased myocardial oxygen consumption and positive inotropy.

PMID- 19770673
TI  - Grapes, wines, resveratrol, and heart health.
AB  - Epidemiological and experimental studies have revealed that a mild to moderate
      drinking of wine, particularly red wine, attenuates the cardiovascular,
      cerebrovascular, and peripheral vascular risk. However, the experimental basis
      for such health benefits is not fully understood. The cardioprotective effect of
      wine has been attributed to both components of wine: the alcoholic portion and,
      more importantly, the alcohol-free portion containing antioxidants. Wines are
      manufactured from grapes, which also contain a large variety of antioxidants,
      including resveratrol, catechin, epicatechin, and proanthocyanidins. Resveratrol
      is mainly found in the grape skin, whereas proanthocyanidins are found only in
      the seeds. Recent studies have demonstrated that resveratrol and proanthocyanidin
      are the major compounds present in grapes and wines responsible for
      cardioprotection. The purpose of this review is to provide evidence that grapes,
      wines, and resveratrol are equally important in reducing the risk of morbidity
      and mortality due to cardiovascular complications. Both wines and grapes can
      attenuate cardiac diseases such as atherosclerosis and ischemic heart disease.
      Recently, wine was also found to increase life span by inducing longevity genes.
      It appears that resveratrol and proanthocyanidins, especially resveratrol,
      present in grapes and wines play a crucial role in cardioprotective abilities of
      grapes and wines.

PMID- 19770674
TI  - Nonlinear distribution of adiponectin in patients with nonalcoholic fatty liver
      disease limits its use in linear regression analysis.

PMID- 19770672
TI  - Nitric oxide-mediated dilation of arterioles to intraluminal administration of
      aldosterone.
AB  - The nature of the rapid action of aldosterone on blood vessels, whether
      endothelium-dependent dilation or smooth muscle-dependent constriction is
      predominant, is still in dispute. In this study, we administered aldosterone
      intraluminally or extraluminally to isolated mesenteric and cerebral arterioles
      of male Wistar rats. Extraluminal administration of aldosterone (10(-11) or 10(
      7) M) elicited a transient vasodilatation. The peak response appeared at
      approximately 5 minutes. In contrast, intraluminal administration of aldosterone
      elicited a greater and sustained dilation. When aldosterone (10(-12)-10(-7) M)
      was administered extraluminally in a cumulative manner, dose-dependent
      vasodilator responses were elicited, except a reduced dilation was observed to
      10(-7) M aldosterone. The dilations were significantly inhibited by
      spironolactone (10(-7) M), a mineralocorticoid receptor antagonist or Nomega
      nitro-l-arginine methyl ester (3 x 10(-4) M), a NO synthesis inhibitor. In
      endothelium-denuded vessels, extraluminal aldosterone induced a dose-dependent
      vasoconstrictor response. Scavenging superoxide with Tempol (10(-4) M) sustained
      the extraluminal aldosterone (10(-11) or 10(-7) M)-induced dilation, whereas
      inhibition of NO synthesis or removal of the endothelium abolished intraluminal
      aldosterone-induced dilation. Dilation to 10(-7) M aldosterone was significantly
      enhanced after inhibition of NAD(P)H-oxidase with apocynin (10(-5) M).
      Furthermore, in the presence of endothelial dysfunction, induced by chronic
      inhibition of NO synthesis, intraluminal administration of aldosterone failed to
      dilate the arterioles. We conclude that in physiological conditions, acute
      elevation of aldosterone will evoke mainly an endothelium-dependent NO-mediated
      dilation.

PMID- 19770675
TI  - The clinical presentation of chronic hepatitis B virus infection in Asian
      Americans: a single center retrospective study.
AB  - BACKGROUND: The clinical course of chronic hepatitis B virus (HBV) infection
      varies with ethnicity. Little is known about the clinical presentation of chronic
      HBV infection in Asian Americans. OBJECTIVES: To define the clinical presentation
      of chronic HBV infection in Asian Americans. METHODS: This is a retrospective
      study that used systematic chart review and statistical analysis to investigate
      213 Asian-American patients with chronic HBV infection who presented to a
      university medical center. RESULTS: This cohort included 55.8% male patients,
      97.9% were born outside the US, and 52.3% reported a family history of HBV
      infection. Of the 56 patients with liver biopsy, 34.0% had stage 3 to 4 fibrosis.
      In patients with available data, 21.5% were hepatitis B e antigen positive [HBeAg
      (+)] and 31.1% had HBV DNA levels >1 x 10(6) copies/mL. Patients with HBeAg (+)
      HBV infection were diagnosed at a younger age (P=0.002) and with higher alanine
      aminotransferase (P=0.001) and HBV DNA (P=0.001) levels. Although only 3.3%
      presented with obesity (ie, body mass index >or=30 kg/m2), 43.4% had evidence of
      hepatic steatosis. Presentation of hepatocellular carcinoma was associated with
      an older age at diagnosis (P<0.001), male sex (P<0.001), tobacco use (P<0.001), a
      greater degree of fibrosis on liver biopsy (P=0.01), and higher alanine
      aminotransferase, aspartate aminotransferase (P<0.001), and a fetoprotein
      (P<0.001) levels. CONCLUSIONS: Chronic HBV infection in foreign-born Asian
      Americans was characterized by a low rate of HBeAg (+) and male predominance as
      well as high rates of family history of HBV infection, hepatic fibrosis, and
      hepatic steatosis.

PMID- 19770676
TI  - Differential diagnosis for intrahepatic biliary cystadenoma and hepatic simple
      cyst: significance of cystic fluid analysis and radiologic findings.
AB  - GOALS: This study evaluated the significance of cystic fluid analysis and
      radiologic findings in the differential diagnosis of biliary cystadenomas (BCA)
      and hepatic simple cysts (HSCs). BACKGROUND: BCA are premalignant lesions. The
      treatment of choice is surgical excision. It is important to differentiate BCA
      from HSCs because they have different clinical significances and treatment plans.
      However, it is difficult to preoperatively differentiate a BCA from a HSC. STUDY:
      This retrospective study was done with 31 patients suffering from pathologically
      diagnosed BCA or HSC. All patients underwent surgery between May 1995 and June
      2008 at a single institution and had cystic fluid analysis preoperatively or
      intraoperatively. RESULTS: We discovered no statistically significant differences
      in cystic fluid carbohydrate antigen 19-9 (CA 19-9) levels or carcinoembryonic
      antigen levels when comparing BCA (n=17) and HSCs (n=14). BCA were significantly
      more frequently associated with female sex (17/17 vs. 10/14, P=0.032), presence
      of a septum (16/17 vs.5/14, P=0.001), and septal thickening (8/17 vs. 1/14,
      P=0.021). All 3 cases with calcifications belonged to the BCA group, but sample
      size was too small to demonstrate statistical significance. There were no
      statistically significant differences in other clinical and radiologic findings
      including age, presence of symptoms, serum tumor markers, serum chemistry, size,
      location, lobulation, septal enhancement, wall enhancement, wall thickening,
      mural nodule, or biliary dilatation. CONCLUSIONS: Cystic fluid carbohydrate
      antigen 19-9 levels and carcinoembryonic antigen levels were not useful for
      differential diagnosis of BCA vs. HSC. BCA were more common than HSCs in females,
      patients with a septum, and patients with septal thickening.

PMID- 19770677
TI  - Homozygous TRPV1 315C influences the susceptibility to functional dyspepsia.
AB  - OBJECTIVES: Capsaicin/vanilloid (transient receptor potential vanilloid 1,
      (TRPV1) receptor has been shown to be expressed in gastrointestinal tract and
      play a role as a member of sensory ion channel superfamily. The G315C
      polymorphism affects the TRPV1 gene and alters its protein level. We aimed to
      investigate the effect of TRPV1 G315C polymorphism on functional dyspepsia (FD)
      in a Japanese population. METHODS: TRPV1 G315C polymorphism was genotyped in 98
      subjects with no upper abdominal symptoms and 109 patients with FD. Severity of 7
      upper gastrointestinal symptoms was assessed during cold water, and cold
      carbonated water drinking for randomly selected 20 healthy subjects. RESULTS: We
      found a significant inverse association between TRPV1 315CC genotype and FD [CC
      vs. others; odds ratio (OR)=0.40, 95% confidence interval (CI)=0.38-0.82]. We
      also found that the same genotype held a lower risk of both epigastric pain
      syndrome (OR=0.25, 95% CI=0.09-0.73), postprandial syndrome (OR=0.27, 95% CI=0.07
      0.96) according to Rome III, and Helicobacter pylori positive FD (OR=0.28, 95%
      CI=0.10-0.79). The evolution of symptom severity scale of 7 total symptoms
      (P=0.004), and heavy feeling in stomach (P=0.02) during cold carbonated water
      drinking were significantly lower among 315CC genotypes compared with others.
      CONCLUSIONS: Homozygous TRPV1 315C influences the susceptibility to FD through
      altering the upper gastrointestinal sensation.

PMID- 19770678
TI  - Colonoscopy performance in a large private practice: a comparison to quality
      benchmarks.

PMID- 19770679
TI  - Limited accuracy of the hyperbaric index, ambulatory blood pressure and
      sphygmomanometry measurements in predicting gestational hypertension and
      preeclampsia.
AB  - OBJECTIVE: The aim of this study was to validate the hyperbaric index (HBI) for
      first trimester prediction of preeclampsia and gestational hypertension. METHODS:
      Participants were low-risk and high-risk nulliparous women and high-risk
      multiparous women, and were recruited between April 2004 and June 2006. At a
      gestational age of 9 weeks (range 8-11 weeks), blood pressure (BP) was measured
      first by sphygmomanometry and thereafter by ambulatory BP measurement (ABPM) for
      48 h. The first 90 low-risk women who had an uneventful pregnancy formed the
      reference group for calculation of a time-specified tolerance interval with 90%
      confidence limits. In the validation group, consisting of the remaining women,
      the HBI was calculated as the time-specified BP excess over this tolerance limit
      for SBP, DBP and mean arterial pressure. RESULTS: The validation group contained
      101 women. Fifteen women developed preeclampsia and 13 developed gestational
      hypertension. For preeclampsia, the maximum HBI had the best predictive capacity
      with a sensitivity of 73% and a specificity of 86%. However, the difference with
      standard ABPM measurement or sphygmomanometry was small with a sensitivity
      between 75 and 73% and a specificity between 86 and 95%. The predictive efficacy
      for gestational hypertension was poor with all methods (sensitivity between 54
      and 77%, specificity between 41 and 78%). CONCLUSION: Standardized
      sphygmomanometry, ABPM measurement and the HBI calculated from 48-h ABPM had a
      comparable, restricted predictive efficacy. The high predictive value of HBI as
      observed in earlier studies could not be reproduced.

PMID- 19770680
TI  - High-salt diet increases plasma adiponectin levels independent of blood pressure
      in hypertensive rats: the role of the renin-angiotensin-aldosterone system.
AB  - BACKGROUND: High sodium intake is associated with increased risk of end-organ
      damage, independent of blood pressure (BP) levels. The protective peptide
      adiponectin may play a role in the pathogenesis of hypertension and particularly
      in salt-loaded conditions. Furthermore, increased adiponectin levels were
      observed in salt-loaded conditions. However, there is little information on the
      direct effect of high-salt diet on plasma adiponectin. The aim of the present
      study was to examine the effect of high-salt diet on adiponectin levels in
      Sprague-Dawley rats and explore the mechanisms that regulate adiponectin levels
      under salt loading. METHODS: Sprague-Dawley rats were fed either standard chow
      diet or medium or high sodium diet for 5 weeks. BP and plasma adiponectin were
      measured at baseline and during the study. In additional studies the same
      protocol was repeated with the addition of clonidine, telmisartan, hydralazine or
      eplerenone. RESULTS: High-salt diet increased systolic BP, suppressed plasma
      aldosterone levels and attenuated body weight gain. Five weeks of salt loading
      increased plasma adiponectin levels in a dose-dependent manner (medium salt and
      high salt were 47 and 93% higher than control, respectively, P < 0.05).
      Hydralazine and clonidine attenuated salt-induced BP increase but did not
      attenuate the increase in adiponectin levels whereas, telmisartan, an angiotensin
      receptor blocker, and eplerenone, an aldosterone blocker, attenuated both the
      increase in BP and in adiponectin levels. CONCLUSIONS: High salt intake increases
      adiponectin levels independent of the increase in BP. This effect is mediated
      through the renin-angiotensin-aldosterone system.

PMID- 19770681
TI  - Acute pancreatitis in children with acute lymphoblastic leukemia treated with L
      asparaginase.
AB  - BACKGROUND: L-asparaginase (L-asp) is used as part of the initial treatment in
      children with acute lymphoblastic leukemia (ALL), inducing remission in 83% to
      95% of the treated patients. Major toxicity effects reported are hypersensitivity
      reactions and dysfunctions of the liver and pancreas. Acute pancreatitis (AP)
      induced by L-asp has been noted in 2.5% to 16% of the treated patients. The
      purpose of this study was to determine the frequency and outcome of AP in
      children with ALL treated with L-asp in a tertiary care pediatric hospital.
      METHODS: From January 1999 to June 2005, the charts of children with ALL admitted
      for L-asp treatment were reviewed. Data from children who developed AP were
      analyzed retrospectively. AP was defined as the presence of clinical data
      (nausea, vomiting, and abdominal pain), elevated pancreatic enzymes, and changes
      in the abdominal ultrasound and/or computed tomography (CT) scan. Clinical and
      biochemical data, abdominal ultrasound, and CT scan findings, complications,
      treatment, and outcome were analyzed retrospectively. RESULTS: During the last 6
      years, 266 ALL new cases were started on chemotherapy including L-asp, of which
      18 of 266 (6.7%) developed AP. Pancreatic necrosis by CT scan was found in 10
      patients, peripancreatic collections and pseudocyst formation were detected in 5
      and 3 cases, respectively, and resolved by cystogastrostomy or drainage. Two
      patients developed chronic pancreatitis and 3 diabetes. There was no relationship
      between number of doses and pancreatic toxicity. None of the patient died due to
      pancreatic toxicity. CONCLUSIONS: L-asp is an effective drug to treat ALL, the
      administration of L-asp requires the monitoring of pancreatic toxicity to detect
      AP and have treatment initiated as early as possible. Chronic complications after
      AP occur in almost one third of cases.

PMID- 19770682
TI  - Two additional cases of childhood embryonal tumors in Brazilian children born
      from assisted reproductive technologies.

PMID- 19770683
TI  - A 13-year-old boy with extensive bilateral lung infiltrates.

PMID- 19770684
TI  - Diagnosis of undifferentiated embryonal sarcoma of the liver-importance of
      combined studies of ultrasound and CT scan.
AB  - Undifferentiated embryonal sarcoma is the uncommon malignant mesenchymal tumor of
      the liver seen in children and young adults. Radiologic findings reflect the
      solid to cystic appearances observed in the gross specimens. The discrepancy in
      the appearances of the mass between the ultrasound scan and computed tomography
      scan is the hall mark of this tumor. Ultrasonography typically show a large mass
      which is hyperechoic or isoechoic (solid). Computed tomography shows cystic
      component of the tumor. This unique radiologic feature will help in the diagnosis
      of the tumour.

PMID- 19770685
TI  - Adjuvant corticosteroid therapy in 2 children with hepatosplenic candidiasis
      related IRIS.
AB  - First described in HIV-infected patients who recently initiated highly active
      antiretroviral therapy, the immune reconstitution inflammatory syndrome (IRIS) is
      best characterized as a collection of inflammatory disorders triggered by rapid
      resolution of immunosuppression. Treatment of IRIS is a clinical challenge due to
      the variety of clinical presentations and the presence of multiple pathogens
      capable of causing the syndrome. Hepatosplenic candidiasis, an uncommon form of
      invasive Candida species infection, was recently suggested to belong to the
      spectrum of fungus-related IRIS. We report 2 cases of probable hepatosplenic
      candidiasis according to the guidelines of the European Organization for Research
      and Treatment of Cancer and the Mycosis Study Group, occurring in pediatric
      patients with acute leukemia during rapid neutrophil recovery after cytotoxic
      chemotherapy. In both cases, abdominal computed tomography scan revealed multiple
      hepatic micronodules, and liver biopsy showed nonspecific granulomatous lesions.
      Hepatosplenic candidiasis symptoms (fever, nausea and vomiting, abdominal pain)
      resolved within 2 days after adjunction of corticosteroid therapy to antifungal
      treatment. Inflammatory markers and related radiologic abnormalities decreased or
      disappeared within 1 month. Recovery of neutrophil count in a context of
      hepatosplenic candidiasis may result in a heightened inflammatory response.
      Corticosteroid therapy in this setting is associated with prompt resolution of
      the symptoms.

PMID- 19770686
TI  - Low dose vincristine-induced severe polyneuropathy in a Hodgkin lymphoma patient:
      a case report (vincristine-induced severe polyneuropathy).
AB  - Chemotherapeutic drugs are the most common toxic agents for peripheral nerves.
      Vincristine is a vinca alkaloid drug that is used for the treatment of several
      malignancies in combination with other chemotherapeutic agents. Treatment with
      intravenous (IV) vincristine at doses above 5 mg leads to a dose-dependent
      neuropathy with sensory symptoms but higher cumulative doses at around 30 to 50
      mg are needed for the development of motor symptoms. The standard maximum adult
      IV vincristine dose is 2 mg IV per dose given at weekly intervals. However,
      administration of a single 2-mg dose IV vincristine may rarely result in the
      development of peripheral neuropathy. Few case reports have been presented on
      vincristine-associated severe paralysis in patients with preexisting hereditary
      neuropathy like Charcot-Marie Tooth (CMT) disease, who received doses even lower
      than 2 mg. Herein, we reported a Hodgkin lymphoma patient who developed severe
      polyneuropathy after receiving 2 mg vincristine treatment and was subsequently
      found to carry the CMT1A duplication responsible for CMT disease.

PMID- 19770687
TI  - Interferon-induced cutaneous sarcoidosis in melanoma.
AB  - Interferon-induced cutaneous sarcoidosis in the adjuvant treatment of melanoma is
      a rare side effect. We present the case of a patient who developed two
      histologically confirmed subcutaneous sarcoid nodules 15 months after starting
      adjuvant therapy with interferon for lymph node metastatic melanoma in which the
      primary tumor was not known. The extension study, coinciding with occurrence of
      the nodules, showed no systemic sarcoidosis. This therefore represents the second
      reported case of interferon-induced cutaneous sarcoidosis in melanoma therapy. As
      computed axial tomography-PET or other imaging techniques are unable to
      differentiate between the radiological signs of melanoma metastasis and
      sarcoidosis, histological evaluation of the granulomatous lesions is essential
      with a view to avoiding unnecessary treatments.

PMID- 19770688
TI  - Static representations of speed and their neural correlates in human area MT/V5.
AB  - Studies have shown that cortical area MT/V5 is activated by visual motion as well
      as illusory motion, implied motion in static images, or motion imagery. Cells
      within these areas are additionally tuned for speed and exhibit different
      responses depending on the actual speed of an object. In this study, we
      investigate the relationship between perceived speed as represented within static
      images and the patterns of activity observed in MT/V5. Consistent with other
      studies, we show robust responses in MT/V5 to implied motion. In addition, our
      results show an increase in the blood-oxygen level dependent response consistent
      with the increased speed information inherent within the images. In the absence
      of any real physical motion, the data illustrate the intricate manner in which
      top-down activity influences visual cortical activity.

PMID- 19770689
TI  - Double decussated ipsilateral corticospinal tract in schizencephaly.
AB  - We report a patient with left hemiparesis because of schizencephaly affecting the
      right precentral gyrus and describe a double decussated ipsilateral corticospinal
      tract detected using the multimodal brain mapping technique. In this patient, we
      could observe that the unaffected primary motor cortex (M1) controls both hands
      by functional magnetic resonance imaging and motor-evoked potential study. We
      were also able to visualize the corticospinal tract originating from the
      unaffected M1 that passed through the internal capsule and cerebral peduncle on
      the same side. It then crossed over twice at the brain stem level to go down to
      the ipsilateral spinal cord. These findings show a unique pattern of brain
      reorganization in the recovery from early brain injury.

PMID- 19770690
TI  - The RNA-binding protein RBM3 is required for cell proliferation and protects
      against serum deprivation-induced cell death.
AB  - Hypoxia and other adverse conditions are commonly encountered by rapidly growing
      cells. The RNA-binding protein RBM3 (RNA-binding motif protein 3), which is
      transcriptionally induced by low temperature and hypoxia, has recently been
      implicated in survival of colon cancer cells by mechanisms involving
      cyclooxygenase-2 (COX-2) signaling. Immunohistochemically, we found strong RBM3
      expression in a variety of malignant and proliferating tissues but low expression
      in resting and terminally differentiated cells. RBM3 expression in fibroblasts
      and human embryonal kidney (HEK293) cells subjected to serum deprivation or
      contact inhibition closely paralleled proliferation rates, assessed by real-time
      RT-PCR and immunoblotting. siRNA-mediated RBM3 knockdown reduced cell viability
      and finally led to cell death, which did not involve caspase-3-mediated
      apoptosis, cell cycle arrest, or COX-2 regulation. In contrast, RBM3 over
      expression rescued cells from death under serum starvation. This was associated
      with increased translation rates, as measured by C serine and H phenylalanine
      incorporation. Together, RBM3 is a critical factor providing cellular survival
      advantages in an adverse microenvironment presumably by restoring translation
      efficacy.

PMID- 19770691
TI  - Early alterations of growth factor patterns in bronchoalveolar lavage fluid from
      preterm infants developing bronchopulmonary dysplasia.
AB  - Chronic lung disease of prematurity (bronchopulmonary dysplasia; BPD) is
      characterized by an arrest in lung development. We hypothesized that early
      alterations in pulmonary expression of growth factors important for normal lung
      development would precede development of BPD. Bronchoalveolar lavage fluid (BALF)
      was obtained from ventilated preterm infants (n = 62) on postnatal d 0, 1, 3, and
      7 and analyzed for total phospholipids (PL), VEGF, PDGF-BB, TGF-alpha and -beta1,
      granulocyte macrophage colony stimulating factor (GM-CSF), and keratinocyte
      growth factor (KGF). Levels (Ln transformed) were compared between infants
      developing BPD and BPD-free survivors, adjusted for potential confounders. BPD
      was associated with higher overall GM-CSF (beta (95% CI) = 0.69 (0.13;1.25); p <
      0.05), lower overall latent TGF-beta1 (beta (95% CI) = -1.19 (-1.87, -0.39); p <
      0.01) and total PL (beta (95% CI) = -0.64 (-1.23, -0.05); p < 0.05), and lower d
      0 and 3 levels of VEGF (mean difference (95% CI) = -1.75 (-2.72, -0.77), p <
      0.001; and -1.18 (-2.30, -0.06), p < 0.05, respectively) and TGF-alpha (mean
      difference (95% CI) = -0.73 (-1.42, -0.04), p < 0.05; and -1.01 (-1.64, -0.38), p
      < 0.01, respectively). Day 0 VEGF levels had the highest predictive value for BPD
      (area under receiver operating characteristic curve = 0.87; p < 0.01). In
      conclusion, substantial alterations in BALF growth factor levels are present in
      infants developing BPD. An early imbalance in pulmonary growth factors may
      contribute to the developmental arrest of the lung seen in BPD. ABBREVIATIONS: :

PMID- 19770692
TI  - Prevalence of cross-reactive HIV-1-neutralizing activity in HIV-1-infected
      patients with rapid or slow disease progression.
AB  - OBJECTIVE: The native envelope gp160 trimer of HIV-1 is thought to shield
      vulnerable epitopes that could otherwise elicit effectively neutralizing
      antibodies. However, little is known about the prevalence of naturally occurring
      broadly neutralizing activity in serum of HIV-1-infected individuals. METHODS:
      Here, we studied 35 participants of the Amsterdam Cohort Studies on HIV-1
      infection (20 long-term nonprogressors and 15 progressors) for the presence of
      cross-reactive neutralizing activity in their sera at 2 and 4 years after
      seroconversion. Neutralizing activity was tested in a pseudovirus assay, against
      a panel of HIV-1 envelope variants from subtypes A, B, C, and D. RESULTS: Already
      at year 2 after seroconversion, seven out of 35 individuals (20%) had cross
      reactive neutralizing activity, which increased to 11 individuals (31%) at 4
      years after seroconversion. There was no difference in the prevalence of cross
      reactive neutralizing serum activity between long-term nonprogressors and
      progressors.Interestingly, high plasma viral RNA load and low CD4(+) cell count
      at set-point were associated with early development of cross-reactive
      neutralizing activity. Neutralization titers in serum increased during the course
      of infection for 91% of individuals studied here, although less rapidly for those
      who did not develop cross-reactive neutralizing activity. CONCLUSION: Overall, we
      here demonstrate a relatively high prevalence of cross-reactive neutralizing
      serum activity in HIV-1-infected patients, which increased with duration of
      infection. These data may imply that immunogenicity of the native envelope spike
      of HIV-1 for eliciting cross-reactive humoral immune responses may be better than
      previously anticipated.

PMID- 19770693
TI  - Evolution and molecular epidemiology of subtype C HIV-1 in Zimbabwe.
AB  - OBJECTIVE: To investigate the origins and evolutionary history of subtype C HIV-1
      in Zimbabwe in a context of regional conflict and migration. DESIGN: HIV-1C pol
      sequence datasets were generated from four sequential cohorts of antenatal women
      in Harare, Zimbabwe sampled over 15 years (1991-2006). METHODS: One hundred and
      seventy-seven HIV-1C pol sequences were obtained from four successive cohorts in
      Zimbabwe. Maximum-likelihood methods were used to explore phylogenetic
      relationships between Zimbabwean HIV-1C sequences and subtype C strains from
      other regions. A Bayesian coalescent-based framework was used to estimate
      evolutionary parameters for HIV-1C in Zimbabwe, including origin and demographic
      growth patterns. RESULTS: Zimbabwe HIV-1C pol demonstrated increasing sequence
      divergence over the 15-year period. Nearly all Zimbabwe sequences clustered
      phylogenetically with subtype C strains from neighboring countries. Bayesian
      evolutionary analysis indicated a most recent common ancestor date of 1973 with
      three epidemic growth phases: an initial, slow phase (1970s) followed by
      exponential growth (1980s), and a linearly expanding epidemic to the present.
      Bayesian trees provided evidence for multiple HIV-1C introductions into Zimbabwe
      during 1979-1981, corresponding with Zimbabwean national independence following a
      period of socio-political instability. CONCLUSION: The Zimbabwean HIV-1C epidemic
      likely originated from multiple introductions in the late 1970s and grew
      exponentially during the 1980s, corresponding to changing political boundaries
      and rapid population influx from neighboring countries. The timing and
      phylogenetic clustering of the Zimbabwean sequences is consistent with an origin
      in southern Africa and subsequent expansion. HIV-1 sequence data contain
      important epidemiological information, which can help focus treatment and
      prevention strategies in light of more recent political volatility in Zimbabwe.

PMID- 19770694
TI  - The effect of HIV infection on adult meningitis in Indonesia: a prospective
      cohort study.
AB  - OBJECTIVE: Indonesia has a concentrated but rapidly growing HIV epidemic. We
      examined the effect of HIV on causative organisms, clinical features and
      prognosis of adult meningitis. DESIGN: A prospective cohort study. METHODS: All
      adult patients at a referral hospital who underwent cerebrospinal fluid
      examination for suspected meningitis were examined for HIV and included in a
      prospective cohort study. Microbiological testing was done for common bacterial
      pathogens, mycobacteria and fungi. Patients were followed for at least 6 months,
      and logistic regression models were used to identify risk factors for mortality.
      RESULTS: Among 185 patients who mostly presented with subacute meningitis, 60%
      were male and the median age was 30 years. HIV infection was present in 25% of
      the patients; almost two-thirds were newly confirmed, and all presented with
      severe immunosuppression (median CD4 cell count 13/microl, range 2-98). One-third
      of HIV-infected patients had cryptococcal meningitis whereas two-thirds suffered
      from tuberculosis. After 1 month, 41% of patients had died. HIV infection was
      strongly associated with 1-month mortality (adjusted odds ratio 12.15; 95%
      confidence interval 3.04-15.72) and death during extended follow-up (hazard ratio
      2.48; 95% confidence interval 1.97-5.74). CONCLUSION: Although HIV is still
      uncommon in the general population in Indonesia, its prevalence among adult
      meningitis cases already seems high. Mycobacterium tuberculosis and Cryptococcus
      neoformans are the main causes of meningitis in this setting, and mortality is
      very high, especially in HIV-infected patients. Our data suggest that adult
      meningitis cases in Indonesia should be screened routinely for HIV infection.
      Further studies are needed to address the high mortality.

PMID- 19770695
TI  - The HIV-1 integrase genotype strongly predicts raltegravir susceptibility but not
      viral fitness of primary virus isolates.
AB  - OBJECTIVE: : Resistance to raltegravir is associated with three genetic pathways
      defined by the mutations Y143R/C, Q148H/R/K or N155H in integrase, which also
      infer a viral fitness cost. Additionally, the three major HIV-1 drug-targeted
      enzymes protease, reverse transcriptase and integrase mature from the same
      polyprotein, suggesting the potential for interaction between them. This study
      aims to elucidate the relative contribution of protease-reverse transcriptase,
      integrase and the rest of the HIV-1 genome to viral fitness and susceptibility to
      raltegravir. METHODS: : Recombinant viruses included integrase, protease-reverse
      transcriptase or the complete pol-coding region from three patients whose
      raltegravir-containing regimen had failed. The first had the mutations
      G140S+Q148H+S230N, the second had Y143R+G163R and the third had no evidence of
      genotypic resistance in integrase. Primary virus isolates were obtained from
      peripheral blood mononuclear cells. In-vitro phenotypic resistance and changes in
      replication capacity were assessed. RESULTS: : Virus isolates, and integrase
      recombinant and pol-recombinant viruses from the patients harboring integrase
      resistance mutations showed a decrease in raltegravir susceptibility, with no
      differences between them. Defects in viral fitness were modulated by resistance
      mutations within protease, reverse transcriptase and integrase, which were
      further compensated by regions outside pol. Moreover, protease-reverse
      transcriptase rescued replication capacity of viruses containing integrase
      resistance mutations, although integrase was unable to compensate defects in
      replication capacity caused by protease-reverse transcriptase resistance
      mutations. CONCLUSION: : Susceptibility to raltegravir is driven by resistance
      mutations in integrase, whereas other viral genes are involved in restoring
      defects in viral fitness in patients whose raltegravir-containing regimen fails,
      suggesting the existence of epistatic effects on replication capacity.

PMID- 19770696
TI  - HIV-associated pulmonary arterial hypertension: survival and prognostic factors
      in the modern therapeutic era.
AB  - OBJECTIVES: To examine baseline characteristics and outcome, and to determine
      variables affecting survival in patients with pulmonary arterial hypertension
      (PAH) associated with HIV infection (PAH-HIV) in the modern era of highly-active
      antiretroviral therapy (HAART) and specific PAH therapy. DESIGN: Retrospective
      review of data from PAH-HIV patients without other associated risk factors for
      PAH, and comparison with previous series. METHODS: Data were reviewed for 77
      consecutive patients treated at the French Reference Centre for Pulmonary
      Hypertension between October 2000 and January 2008. Results were expressed as
      median [1st-3rd quartile] values. RESULTS: At diagnosis of PAH, 81% patients were
      on HAART, 79% had a CD4+ count more than 200 cells/microl and 49% had
      undetectable HIV load. New York Heart Association functional class assessment was
      II (22%), III (69%), and IV (9%). Six-minute walk distance (6MWD) was 375 [288
      421] m, and pulmonary vascular resistance was 689 [524-852] dyn s/cm(5). All
      patients received HAART irrespective of HIV disease stage. Specific PAH therapy
      was started in 50 patients and led to improvements in 6MWD and haemodynamic
      parameters. In patients who did not receive specific PAH therapy, 6MWD improved
      but haemodynamics did not change. Overall survival rate was 88% at 1 year and 72%
      at 3 years. On multivariate analysis, cardiac index more than 2.8 l/min per m(2)
      and CD4+ lymphocyte count more than 200 cells/microl were independent predictors
      of survival. CONCLUSION: In patients with PAH-HIV, HAART seems unable to improve
      haemodynamic parameters. Prognosis in PAH-HIV is mainly related to CD4+
      lymphocyte count and cardiac function.

PMID- 19770697
TI  - Interleukin-10 responses to therapeutic vaccination during highly active
      antiretroviral therapy and after analytical therapy interruption.
AB  - We investigated whether therapeutic vaccination in highly active antiretroviral
      therapy (HAART)-treated patients with a modified vaccinia virus Ankara-vectored
      HIV-1 vaccine, with or without therapy interruption, induced the production of
      interleukin (IL)-10. Plasma IL-10 levels were not significantly increased
      postvaccination, but increased in parallel with viraemia in patients who
      interrupted therapy. Surprisingly, IL-10 blockade augmented HIV-specific T cell
      proliferative responses in HAART-suppressed patients but had no effect once
      virological control was lost. Modulation of IL-10 might enhance vaccine-induced
      immune responses.

PMID- 19770698
TI  - Early mortality and cause of deaths in patients using HAART in Brazil and the
      United States.
AB  - OBJECTIVE: To compare the early mortality pattern and causes of death among
      patients starting HAART in Brazil and the United States. METHODS: We analyzed the
      combined data from two clinical cohorts followed at the Johns Hopkins AIDS
      Service in Baltimore, United States, and the Evandro Chagas Clinical Research
      Institute AIDS Clinic in Rio de Janeiro, Brazil. Participants included those who
      entered either cohort between 1999 and 2007 and were antiretroviral naive. Follow
      up was at 1 year since HAART initiation. Cox proportional hazards regression
      analysis was used to assess the role of the city on the risk of death. RESULTS: A
      total of 859 and 915 participants from Baltimore and Rio de Janeiro,
      respectively, were included. In Rio de Janeiro, 64.7% of deaths occurred within
      90 days of HAART initiation; in Baltimore, 48.9% occurred between 180 and 365
      days. AIDS-defining illness (61.8%) and non-AIDS-defining illness (55.6%)
      predominated as causes of death in Rio de Janeiro and Baltimore, respectively.
      Risk of death was similar in both cities (hazard ratio 1.04; P value = 0.95)
      after adjusting for CD4 T cell count, age, sex, HIV risk group, prior AIDS
      defining illness, and Pneumocystis jirovecii pneumonia and Mycobacterium avium
      prophylaxis. Individuals with CD4 T cell count less than or equal to 50
      cells/microl (hazard ratio 4.36; P = 0.001) or older (hazard ratio, 1.03; P =
      0.03) were more likely to die. CONCLUSION: Although late HIV diagnosis is a
      problem both in developed and developing countries, differences in the timing and
      causes of deaths clearly indicate that, besides interventions for early HIV
      diagnosis, different strategies to curb early mortality need to be tailored in
      each country.

PMID- 19770699
TI  - Bilateral expanded cervico-pectoral "super-thin flap" for entire neck
      reconstruction.
AB  - The anterior neck is a difficult area to reconstruct because the neck connects
      the head and body with multidirectional and complex motility. In this article, we
      demonstrate our cases of reconstruction with bilateral cervico-pectoral "Super
      thin flaps," and discuss our reconstructive methods and results. In this study,
      we analyze 7 cases (male: 4, female: 3) entire anterior neck reconstruction.
      Fourteen expanded flaps were employed for their reconstruction. Flap size, flap
      viability, donor site closure method, esthetic and functional results, and follow
      up term were analyzed retrospectively. Flap sizes ranged from 8 x 6 cm to 17 x 10
      cm. All flap donor sites were closed primarily. All cases achieved full range of
      motion of the neck after the operation by complete removal of contractured
      tissues. Natural cervical contour was achieved in 6 patients (86%). Esthetic
      outcomes were rated to be very good in 4 cases (57%) and good in 2 cases (29%).
      Expanded cervico-pector super-thin flaps combine the techniques of "flap
      thinning" and "flap expansion," and the study indicates that flaps are useful for
      the reconstruction of entire anterior neck.

PMID- 19770700
TI  - Coverage of clavicular area by a pectoralis minor pedicle flap: anatomical study
      and description of three clinical cases.
AB  - As the data in the literature concerning the vascularization of the pectoralis
      minor were conflicting, we conducted a new anatomic study on cadavers preliminary
      to clinical application of a pedicle flap for clavicular coverage in 3 patients.
      Twenty flaps were dissected, yielding numerous anatomic variations. In all cases,
      the principal arteries penetrated the muscle in its upper part, either
      posteriorly or posterolaterally. This anatomic study justified the use of the
      pectoralis minor as a pedicle flap, with turnover just below the coracoid
      process. Accordingly, 3 cases of clavicular defects were treated successfully.
      Reports in the literature propose an adipofascial turnover flap or a pectoralis
      major flap for clavicular coverage. The pectoralis minor pedicle flap is easy to
      dissect and reproducible, involving minor esthetic sequelae and no functional
      complications. This flap, which has never been described in this application,
      would appear to be suitable for first-line treatment in this indication.

PMID- 19770701
TI  - Salvage of a lower extremity by microsurgical transfer of tibial bone from the
      contralateral extremity traumatically amputated at the ankle level.
AB  - The authors present a case of free vascularized transfer of the tibial bone as an
      osteomyocutaneous flap based on the posterior tibial vessels. A 42-year-old man
      presented with severe crush injury to bilateral legs. The left tibial bone and
      soft tissue defect required reconstruction with an osteomyocutaneous free flap.
      Since the contralateral leg was traumatically amputated at the level of the
      ankle, a decision was made to harvest a free tibial osteomyocutaneous flap with
      below-knee-amputation completed. The transfer was achieved successfully with
      complete survival of the flap and bony union. This report describes the technical
      and healing aspects of such a unique transfer which may rarely be indicated.

PMID- 19770702
TI  - Single stage reconstruction of ruptured tendoachilles tendon with skin cover
      using distally based superficial sural artery flap.
AB  - Ruptured tendoachilles along with skin defect is a complex problem to
      reconstruct. Both things require a priority. Single stage reconstruction of
      ruptured tendoachilles tendon with skin cover using distally based superficial
      sural arterial flap allows us to perform both. This procedure gives excellent
      result, shortens the stay, thereby reducing the cost. This method is a simple
      solution to the complex problem like ruptured tendoachilles with skin defect. In
      this study, 6 patients with rupture of tendoachilles tendon due to penetrating
      injury, with skin defect are presented. The repair was done using aponeurotic
      part of tendoachilles tendon, taken from proximal part of tendoachilles in the
      midline measuring around 2 to 2.5 cm in width and 8 to 10 cm in length, with
      intact distal attachment. The tendon was turned upside down by 180 degrees and
      sutured to the distal stump of the tendoachilles tendon without tension. The skin
      defect was covered using distally based superficial sural artery flap in the same
      sitting. The follow-up period was 9 to 30 months. All patients showed good
      results. In one patient there was distal necrosis of 1.5 cm of the distally based
      superficial sural artery flap, which healed satisfactorily with conservative
      treatment. Single stage tendoachilles reconstruction can be used with good
      functional result and patient satisfaction.

PMID- 19770703
TI  - The efficacy of the surgical delay procedure in pedicle TRAM breast
      reconstruction.
AB  - Although experimental evidence suggests that the preliminary surgical delay
      procedure physiologically improves the circulation of the TRAM flap, there are no
      published controlled studies evaluating the clinical outcomes associated with
      this procedure. The purpose of this study was to evaluate the efficacy of the
      surgical flap delay versus no delay in consecutive patients having pedicle TRAM
      breast reconstruction. This was a retrospective cohort study of breast cancer
      patients at the University of Michigan who had pedicle TRAM reconstruction
      between January 2004 and March 2008. Prior to September 2005, all patients had
      pedicle TRAM reconstruction without the delay procedure. Starting in September
      2005, all patients had the delay procedure prior to TRAM flap reconstruction.
      Descriptive statistics were used to compare demographic data, comorbidities, and
      complication rates between the 2 cohorts. Regression analysis was used to
      determine the effects of the surgical delay procedure on the incidence of flap
      ischemia and major and minor complications while controlling for patient and
      treatment level factors. Eighty-seven postmastectomy breast cancer patients had
      unipedicle TRAM flap reconstruction, in which 112 flaps were used to reconstruct
      breasts. The nondelay cohort consisted of 42 consecutive patients (51 flaps) and
      the delay cohort consisted of 45 consecutive patients (61 flaps). Of the patients
      without the surgical delay procedure 17.6% experienced at least one ischemic
      complication of the flap compared with 6.6% of those who were surgically delayed
      (P = 0.082). When controlling for patient and treatment level factors, the delay
      procedure was found to significantly decrease the incidence of flap ischemia (OR
      = 0.21, P = 0.018). In addition, there were no significant differences in the
      incidence of major or minor complication rates in the surgically delayed versus
      nondelayed groups (P = 0.247, P = 0.486, respectively). When patient and
      treatment level factors were taken into consideration, undergoing the delay
      procedure also did not increase the incidence of having a major or minor
      complication. These data support the use of the preliminary surgical delay
      procedure to decrease ischemic complications of the flap in pedicle TRAM
      postmastectomy breast reconstruction.

PMID- 19770705
TI  - Correlation of rapid phenotypic changes and insulin production of differentiated
      human adipose tissue-derived stem cells.
AB  - The study investigates adipose tissue-derived stem cells (ADSCs) to differentiate
      into insulin-secreting cells in vitro. ADSCs were exposed to differentiation
      medium or control medium. Culture medium was harvested for quantification of
      insulin and cells were classified into stages of differentiation ranging from
      normal appearance to islet-like clusters. Morphologic analysis demonstrated
      marked phenotypic changes towards the islet cell lineage. Thirty-six percent of
      cells exposed to differentiation medium had progressed to morphologic end-stage
      after 15 days. Chemiluminescence of the culture medium determined that insulin
      secretion by differentiated cells progressively increased, reaching a maximum at
      day 7. Insulin secretion by control cells was significantly less at all time
      points. A high correlation of secreted insulin and the presence of stage 3 cells
      were observed throughout the entire experiment. ADSCs can be differentiated into
      insulin-secreting cells in response to defined culture conditions. The secreted
      insulin significantly correlates with phenotypic changes throughout the
      differentiation process.

PMID- 19770704
TI  - Reconstruction of canine mandibular bone defects using a bone transport
      reconstruction plate.
AB  - OBJECTIVES: Reconstruction of mandibular segmental bone defects is a challenging
      task. This study tests a new device used for reconstructing mandibular defects
      based on the principle of bone transport distraction osteogenesis. METHODS:
      Thirteen beagle dogs were divided into control and experimental groups. In all
      animals, a 3-cm defect was created on one side of the mandible. In 8 control
      animals, the defect was stabilized with a reconstruction plate without further
      reconstruction and the animals were killed 2 to 3 months after surgery. The
      remaining 5 animals were reconstructed with a bone transport reconstruction
      plate, comprising a reconstruction plate with attached intraoral transport unit,
      and were killed after 1 month of consolidation. RESULTS: Clinical evaluation,
      cone-beam CT densitometry, three-dimensional histomorphometry, and docking site
      histology revealed significant new bone formation within the defect in the
      distracted group. CONCLUSION: The physical dimensions and architectural
      parameters of the new bone were comparable to the contralateral normal bone. Bone
      union at the docking site remains a problem.

PMID- 19770706
TI  - Molecular evidence for the neoplastic potential of hepatic Von-Meyenburg
      complexes.
AB  - Von-Meyenburg complexes (VMCs) have been shown to progress to cholangiocarcinoma
      (CC) in some cases. Histologic examination in such cases reveals a gradual
      transition of VMCs to intermediate lesions and finally to CC. The goal of this
      study was to determine if this histologic progression was also accompanied by
      sequential genetic alterations. Two cases that showed many VMCs with a transition
      to cholangiocarcinoma through intermediate lesions were analyzed. Multiple VMCs
      (away from the tumor), intermediate lesions and areas of frank CC were
      microdissected under stereoscopic guidance and were analyzed for allelic
      imbalance [loss of heterozygosity (LOH)] using a panel of 20 polymorphic
      microsatellite markers by polymerase chain reaction/electrophoresis. The 2 cases
      of CCs revealed LOH at 5 and 7 different genomic loci specific for each patient,
      respectively. Coexisting VMCs also exhibited LOH ranging from 0 to 3 loci in each
      case. Intermediate lesions showed LOH at a single locus in case 1, whereas the
      assay could not be performed in case 2 due to inadequate DNA yield. In case 2,
      the earliest acquired mutations were present in the VMCs supporting a causal
      relationship for neoplastic progression. Discordant LOH mutations were also
      present in the VMCs and the adenomatous lesions providing support that LOH
      detected at these sites did not passively migrate or reflect contamination. The
      results of the present study show that the histologic progression observed
      through these stages is also accompanied by LOH at loci harboring key oncogenes.
      The findings also support that VMCs are preneoplastic lesions that could progress
      to CC with time.

PMID- 19770707
TI  - Immunohistochemical study as a tool in differential diagnosis of pediatric
      malignant rhabdoid tumor.
AB  - Malignant rhabdoid tumors (MRTs) are aggressive childhood neoplasms, occurring
      mainly in the kidney and brain. We describe 2 unusual cases of extrarenal and
      noncranial location (liver and soft tissue with dissemination) mimicking
      hepatoblastoma, neuroblastoma or Ewing sarcoma. Both cases revealed a
      polyphenotypic profile, combined with cytokeratin, vimentin, and CD99 expression.
      INI1/BAF-47 showed negative protein nuclear expression in both cases, suggesting
      a diagnosis of MRT. An extensive immunohistochemical panel was performed to
      exclude pediatric tumors reminiscent of MRT. The genetic studies failed to
      detected MYCN amplification, 11q23 deletion, and EWS break-apart positivity. No
      alterations of 22q integrity were demonstrated with the probes used for the study
      (N25 Di George/22q11.2, 22qter, and EWS/22q12). We discuss the differential
      diagnosis in pediatric polyphenotypic tumors (Wilms tumor, neuroblastoma,
      desmoplastic small round cell tumor, and Ewing sarcoma). Analysis of INI1/BAF-47
      expression can offer important clues in the diagnosis of pediatric tumors with
      rhabdoid phenotype. The integration of clinical, morphologic,
      immunohistochemical, and genetic data is required to approach a correct diagnosis
      of pediatric tumor in unusual location with atypical or undifferentiated
      morphology.

PMID- 19770708
TI  - Peripheral endothelial cell damage after trephination of donor tissue.
AB  - PURPOSE: To evaluate and quantify the degree and pattern of donor endothelial
      cell damage, which occurs with mechanical trephination of donor corneal tissue.
      METHOD: Twenty donor corneal-scleral tissues were used for these paired
      experiments. The tissues were randomized for trephination with 10 tissues
      trephinated by an 8.0-mm-diameter Barron trephine (Katena, Denville, NJ), and 10
      tissues trephinated with an 8.0-mm-diameter UltraFit Coronet trephine
      (distributed by Angiotech, British Columbia, Canada) by the same investigator.
      Trephinated corneal buttons were then stained with vital dye stain, and the
      endothelial layer image captured with digital photography. The images were then
      analyzed by digital planimetry, and the pattern and quantity of endothelial
      damage was determined by an investigator who was masked to the specific trephine
      used for the individual tissue. RESULTS: Trephination created a pattern of
      circular damage at the edge of the donor button in every case with no break in
      continuity of the circle, but some portions of the circle were wider than others.
      Occasional, scattered, peripheral small areas also displayed damage, but no
      significant striae, stretch, or other central damage was noted in any donor. The
      mean percent damage in the series was 6.35% +/- 0.90% (range: 4.33%-7.78%). The
      UltraFit Coronet trephinations averaged damage of 5.64% +/- 0.85% (range: 4.33%
      6.69%), and the Barron trephinations averaged damage of 6.50% +/- 0.95% (range:
      4.92%-7.78%). Although 8 of 10 experimental pairs of trephinations demonstrated
      less peripheral endothelial damage with the UltraFit Coronet trephine, the mean
      damage between each group did not reach statistical significance in this small
      series. (P = 0.08) CONCLUSIONS: Donor mechanical trephination of full-thickness
      corneal tissue creates relatively consistent amounts of peripheral edge damage
      and likely no central endothelial damage. There may exist differences in edge
      damage between different mechanical trephination systems, and a direct comparison
      to laser-created trephination is needed.

PMID- 19770709
TI  - Guinea pig models of acute keratitis responses.
AB  - PURPOSE: Contact lens acute red eye (CLARE) and infiltrative keratitis (IK) are
      inflammatory responses of the eye associated with extended wear of soft contact
      lenses and are associated with bacterial colonization of contact lenses.
      Development of animal models to study these conditions is of importance in
      confirming risk factors and developing preventative strategies. METHODS: Silicone
      hydrogel contact lenses contaminated with a human CLARE isolate of Pseudomonas
      aeruginosa at inocula ranging from 1 x 10 to 6 x 10 colony-forming units (CFUs)
      for 15 minutes, 1 hour, or 24 hours were worn by guinea pigs for times up to 48
      hours in 3 models designed to simulate contamination during wear and contact lens
      care regimens. Eyes were examined by slit-lamp biomicroscopy and histology to
      evaluate ocular responses and inflammation. RESULTS: Three different models for
      the effects of bacterial contamination on the etiology of CLARE/IK were developed
      and tested in the guinea pig eye. Bacterial contamination of contact lenses was
      confirmed to be a major risk factor for the development of CLARE/IK and a dose
      response shown. The pathological features of CLARE/IK in the guinea pig were
      virtually identical to those observed in human eyes. CONCLUSION: The models
      characterized here provide a useful tool for development of interventional and
      therapeutic strategies for these important ocular inflammatory conditions.

PMID- 19770711
TI  - Relaxing incisions combined with adjustment sutures for post-deep anterior
      lamellar keratoplasty astigmatism in keratoconus.
AB  - PURPOSE: To find an effective and reliable method to correct astigmatism after
      deep anterior lamellar keratoplasty (DALK) in patients with keratoconus. PATIENTS
      AND METHODS: This interventional case series included 14 eyes of 14 patients with
      keratoconus (12 males) undergoing graft refractive surgery (GRS) for intolerable
      post-DALK astigmatism. The technique of GRS for the 5 initial cases consisted of
      only relaxing incisions at the steep meridian in the graft-host interface down to
      Descemet membrane. For the rest, the relaxing incisions at the steep meridian
      were accompanied by simultaneous suturing and the effect of the relaxing
      incisions was controlled through selective suture removal starting a few days
      after the operation. The main outcomes were uncorrected and corrected visual
      acuity and change in refractive and keratometric astigmatism using subtraction
      and vector analysis methods. RESULTS: Mean patient age was 29.36 +/- 6.2 years.
      Mean time interval from complete suture removal to GRS and follow-up period were
      4.5 +/- 2.0 months and 12.0 +/- 7.4 months, respectively. Mean preoperative best
      corrected visual acuity was 0.29 +/- 0.1, increasing to 0.22 +/- 0.1 logarithm of
      minimum angle of resolution after the operation (P = 0.007). Average keratometric
      astigmatism was reduced by 3.8 and 5.5 diopters measured with subtraction and
      vector analysis methods, respectively. Four of 5 eyes that had only relaxing
      incisions initially required suturing of the incisions because of overcorrection,
      whereas preliminary results showed none of the 9 patients undergoing simultaneous
      relaxing incisions and suturing required further intervention. CONCLUSION:
      Relaxing incisions and suturing at the steep meridian followed by selective
      suture removal can effectively and predictably reduce post-DALK astigmatism in
      patients with keratoconus.

PMID- 19770710
TI  - Intraoperative mitomycin C and corneal endothelium after pterygium surgery.
AB  - PURPOSE: To determine the effect of mitomycin C (MMC) on the corneal endothelium
      after primary pterygium surgery. METHODS: This prospective, interventional,
      nonrandomized, observer-masked study included 46 consecutive patients (51 eyes)
      with primary pterygium. The bare sclera technique with 1-minute application of
      0.02% MMC intraoperatively was used in all cases. The follow-up period was 3
      months. Preoperative and postoperative central corneal specular microscopy was
      performed. The endothelial cell density, coefficient of variation of cell size,
      and percentage of hexagonal cells were analyzed, and the corneal thickness was
      measured. RESULTS: The mean endothelial cell densities preoperatively and 3
      months postoperatively were 2382.35 +/- 342.07 cells per square millimeter
      (range, 1020-3129) and 2385.02 +/- 356.83 cells per square millimeter (range,
      1001-3151), respectively (P = 0.96). The mean coefficients of variation of cell
      size preoperatively and 3 months postoperatively were 34.31 +/- 5.62 (range, 22
      49) and 35.29 +/- 7.50 (range, 22-55), respectively (P = 0.17). The mean
      percentages of hexagonal cells values preoperatively and 3 months postoperatively
      were 52.98 +/- 7.32 (range, 32-71) and 51.61 +/- 8.98 (range, 32-67),
      respectively (P = 0.48). The mean pachymetry measurements preoperatively and 3
      months postoperatively were 506.65 +/- 36.87 microm (range, 411-583) and 502.08
      +/- 41.33 microm (range, 411-593), respectively (P = 0.99). CONCLUSIONS: One
      intraoperative application of 0.02% MMC for 1 minute after primary pterygium
      surgery does not seem to cause substantial changes in the corneal endothelium at
      3 months.

PMID- 19770712
TI  - Ten-year follow-up of graft survival and visual outcome after penetrating
      keratoplasty in Sweden.
AB  - PURPOSE: To determine factors influencing graft survival and visual outcome 10
      years after penetrating keratoplasty. METHODS: Ten-year follow-up data were
      obtained from a cohort of patients that represented 20% of corneal transplants in
      Sweden between 1996 and 1998. Multiple regression analyses (logistic and linear)
      were performed on graft survival and visual outcome (visual acuity and
      astigmatism). RESULTS: Of the initial 242 patients receiving a corneal transplant
      during 1996-1998, 140 were available at 10 years. The majority of patients lost
      to follow-up had the indication bullous keratopathy and many were deceased.
      Overall, 71% of transplants available for follow-up at 10 years were still
      functioning, with keratoconus showing the best result (88%) and bullous
      keratopathy the worst (48%). Complications during the first 2 postoperative years
      reduced the percentage of functioning grafts at 10 years from 84% to 50%. The
      visual acuity was influenced by indication and postoperative complications. The
      change in Snellen lines between preoperative and 10-year visual acuity for the
      individual patients also depended on indication and postoperative complications.
      Most of the changes occurred during the first 2 postoperative years. The
      astigmatism at 10 years was also affected by postoperative complications and in
      addition by the amount of astigmatism at 2 years. CONCLUSION: Graft survival and
      visual outcome at 10 years depended on indication and postoperative
      complications. Most improvement of vision occurred during the first 2 years and
      was predictive of the 10-year visual outcome.

PMID- 19770713
TI  - High-frequency topical cyclosporine 0.05% in the treatment of severe dry eye
      refractory to twice-daily regimen.
AB  - PURPOSE: The purpose of this study was to report the efficacy of topical
      cyclosporine 0.05% at a frequency of 3 to 4 times daily in severe dry eye
      disease. METHODS: We retrospectively identified a cohort of patients with severe
      dry eye disease who had shown inadequate response to at least a 4-month course of
      treatment with twice-daily use of topical cyclosporine 0.05% but who showed
      significant improvement to more frequent dosing. RESULTS: Twenty-two patients,
      including 13 patients with ocular graft-versus-host disease and 9 patients with
      primary or secondary Sjogren's syndrome, were included. After a minimum of a 2
      month course of treatment with more frequent dosing of cyclosporine 0.05% (3
      times a day in 7 patients and 4 times a day in 15 patients), overall dry eye
      symptoms were improved in 15 (68.2%) patients (9 patients with ocular graft
      versus-host disease and 6 patients with Sjogren's syndrome). Mean corneal
      fluorescein staining scores (National Eye Institute scale of 0-15) improved
      (decreased) from the baseline (precyclosporine use) by -3.5 (range, 0 to -7) in
      patients with ocular graft-versus-host disease (P < or = 0.0008) and -2.8 (range,
      0 to -5) in patients with Sjogren's syndrome (P < or = 0.001). After treatment
      with high-frequency use of cyclosporine 0.05%, the global physician assessment of
      dry eye status was favorable (improved) in 16 (72.7%) patients. Three (13.6%)
      patients reported new-onset symptoms of burning or irritation with the use of
      high-frequency dosing of topical cyclosporine. No other associated adverse effect
      was reported. CONCLUSION: These data suggest that patients with severe dry eye
      may require more frequent dosing of topical cyclosporine 0.05% than twice daily.

PMID- 19770714
TI  - Iris melanoma arising from sector congenital ocular melanocytosis in a child.
AB  - PURPOSE: To report a clinicopathologic correlation of a melanoma arising from
      iris component of ocular melanocytosis in a child. METHODS: A 13-year-old boy
      developed a progressive iris nodule arising from sector iris pigmentation that
      was a component of congenital ocular melanocytosis involving the iris, ciliary
      body and choroid. The tumor was examined clinically and with ultrasound
      biomicroscopy (UBM), removed by peripheral iridocyclectomy, and studied
      histopathologically. RESULTS: Clinically, the pigmented nodule was 3 mm in
      diameter, located within the sector iris pigmentation, and was 2.4 mm in
      thickness as measured by UBM. Histopathologically, it was composed predominately
      of spindle B melanoma cells with adjacent spindle and dendritic melanocytes
      compatible with iris melanocytosis. CONCLUSION: Although highly unusual, melanoma
      can arise in the sector iris pigmentation that is often a component of congenital
      ocular melanocytosis. Even young patients with ocular melanocytosis should be
      examined periodically for development of melanoma in the ciliary body and
      choroid.

PMID- 19770715
TI  - Conjunctival lichen planus simulating ocular surface squamous neoplasia.
AB  - PURPOSE: To describe the history and clinical presentation of a case of
      conjunctival lichen planus simulating ocular surface squamous neoplasia (OSSN).
      METHODS: A 32-year-old Hispanic man presented with a 6-month history of worsening
      foreign body sensation, localized conjunctival hyperemia, and a progressively
      enlarging "bump" located in the temporal aspect of his right eye. The patient
      denied any prior ocular trauma or surgery to the affected eye. Evaluation
      consisted of slit lamp examination and surgical excision of the mass with
      histopathologic studies. RESULTS: Slit lamp examination revealed the presence of
      a 6 x 5 x 1 mm elevated conjunctival fleshy mass that extended into the corneal
      limbus in the right eye. The lesion exhibited intrinsic pigmentation and
      vascularization as well as the presence of a dilated feeder vessel. Based on
      clinical findings, a diagnosis of OSSN was suspected. An excisional biopsy was
      performed with cryotherapy application to the surgical margins. Histopathologic
      study of the lesion revealed hyperkeratosis, parakeratosis, irregular acanthosis,
      and a band-like infiltrate of predominantly lymphocytes hugging the epithelium,
      consistent with the diagnosis of lichen planus. CONCLUSION: Ocular lichen can
      present as a focal conjunctival lesion. Excisional biopsy allowed us to make the
      diagnosis of this rare entity, which presented as a simulating lesion with
      clinical features consistent with ocular surface squamous neoplasia.

PMID- 19770716
TI  - Fixed dilated pupil (urrets-zavalia syndrome) after deep anterior lamellar
      keratoplasty.
AB  - PURPOSE: To report 4 cases that developed fixed dilated pupil after deep anterior
      lamellar keratoplasty (DALK) for treating keratoconus and granular corneal
      dystrophy. METHODS: Four patients underwent DALK (either Melles's manual
      dissection or Anwar's big-bubble technique) with diagnosis of keratoconus (2
      cases) and granular corneal dystrophy (2 cases). In Melles's technique, the
      anterior chamber was fully filled with air at the beginning of procedure. When
      corneal dissection was complete, air was replaced with balanced salt solution. In
      Anwar's technique, a large bubble was formed between Descemet's membrane and the
      deepest stroma. Viscoelastic was not used within the anterior chamber in either
      technique. For microperforation, air was left in the anterior chamber for a
      couple of days. Two patients developed severe fibrinous anterior uveitis that was
      controlled with intense topical and systemic steroid. Other two patients
      developed high intraocular pressure that was controlled with antiglaucoma
      medications. RESULTS: After 1-2 weeks, all 4 DALK patients developed fixed
      dilated pupil and posterior synechiae; 2 patients developed a faint anterior
      subcapsular opacity. Of 286 patients who underwent DALK, 6 patients had
      microperforation (2%) and 4 patients developed fixed dilated pupil (1.4%). Best
      corrected visual acuity (BCVA) decreased in all patients; most of them complained
      about visual symptoms like glare and halo at night. CONCLUSIONS: Fixed dilated
      pupil (Urrets-Zavalia syndrome) is an uncommon but rather serious complication of
      corneal transplantation. Iris ischemia is the most common proposing mechanism.
      Decreased BCVA and visual symptoms at night (glare and halo) are late sequelae.A
      fixed dilated pupil with iris atrophy (Urrets-Zavalia syndrome) is an uncommon
      postoperative complication that was originally described after penetrating
      keratoplasty for keratoconus. In these cases, the iris is fixed and dilated and
      adheres to anterior lens capsule. Prepupillary iris atrophy is usually seen and
      may be accompanied by a severe fibrinous reaction and anterior subcapsular lens
      opacity.

PMID- 19770717
TI  - Occult open globe injury in a patient with corneal foreign body: a case report.
AB  - PURPOSE: To demonstrate the role of ultrasonographic biomicroscopy in diagnosing
      occult open globe injury. METHOD: A 50-year old man presented with a 2-day
      history of a corneal foreign body caused by a missile injury. Slit lamp
      biomicroscopy showed an intrastromal corneal foreign body measuring 0.7 x 0.7 mm,
      situated at the visual axis. Seidel test was negative. Full thickness corneal
      penetration could not be ruled out and an ultrasonographic biomicroscopy
      examination was subsequently performed. RESULTS: Ultrasonographic biomicroscopy
      revealed a probable full thickness corneal penetration. The patient was diagnosed
      with penetrating corneal injury. CONCLUSION: Ultrasonographic biomicroscopy has
      an important role in the diagnosis of occult open globe injury.

PMID- 19770718
TI  - Ocular cicatricial pemphigoid: the role of scleral lenses in disease management.
AB  - PURPOSE: The purpose of this study is to report a case of fluid-ventilated
      scleral rigid gas permeable lens use in the management of ocular cicatricial
      pemphigoid. METHODS: A 74-year-old woman was referred to our clinic in May 2007
      with a 4-year history of ocular pain and declining visual acuity. She had been
      diagnosed with ocular cicatricial pemphigoid by her previous eye care provider.
      Despite aggressive systemic and topical therapy, she developed persistent corneal
      epithelial defects in both eyes (3 mm in diameter OD, 4 mm x 8 mm OS). Her best
      spectacle-corrected visual acuity was significantly reduced (20/150 OD, hand
      motion OS). She was fit with Jupiter scleral lenses for continuous wear to help
      preserve corneal integrity and visual function. RESULTS: Within 6 weeks of
      initiation of scleral lens wear, her corneal epithelial defects had healed and
      progression of stromal thinning was arrested. Her visual acuity with the scleral
      lenses was 20/50 OD and hand motion in the left eye. Her ocular surface and
      visual function have been maintained for 17 months after the initiation of
      scleral lens wear. CONCLUSIONS: If severe ocular cicatricial pemphigoid threatens
      corneal integrity despite traditional management, scleral contact lenses may play
      a role in the visual rehabilitation and ocular surface protection in select
      patients with this disease.

PMID- 19770720
TI  - Bilateral epibulbar xanthomas--a case report.
AB  - PURPOSE: To report bilateral epibulbar xanthomatous lesions in an adult with a
      normal serum lipid profile and no cutaneous or systemic features of a histiocytic
      disease. METHODS: Clinicopathologic report. RESULTS: A 44-year-old man presented
      with gradually enlarging yellow epibulbar masses in both eyes. The lesions had
      recurred after excisions performed 2 years previously. Systemic evaluation was
      normal. Excisional biopsies were performed, and histological examination revealed
      numerous foamy histiocytes with scattered Touton giant cells and lymphocytes. No
      recurrence was observed after 1 year of follow-up. CONCLUSION: Xanthomatous
      epibulbar lesions are exceedingly rare and may occur as an isolated finding.
      Evaluation should be directed toward detecting underlying non-Langerhans cell
      histiocytic diseases and disorders of lipid metabolism. Recurrent lesions may be
      successfully treated by surgical excision.

PMID- 19770719
TI  - Attenuation of ocular hypertension with the use of topical loteprednol etabonate
      0.5% in steroid responders after corneal transplantation.
AB  - PURPOSE: To describe a clinically observed reduction in intraocular pressure
      (IOP) without increased allograft rejection in known "steroid responders" using
      loteprednol etabonate 0.5% ophthalmic suspension as second-line rescue therapy
      after corneal transplantation. METHODS: Medical records from a prespecified 15
      month period were retrospectively reviewed for all post-corneal transplant
      patients in whom loteprednol etabonate was initiated and prednisolone acetate
      1.0% ophthalmic suspension withdrawn because of a secondary increase in IOP.
      Elevated postoperative IOP was defined as IOP that increased > or =21 mm Hg.
      Baseline IOP values were compared with IOP readings at follow-up examinations,
      with data points set retrospectively at 0-4, 4-8, 8-16, 16-32, and >32 weeks.
      Patient records were evaluated for any signs of allograft rejection during
      loteprednol etabonate therapy. RESULTS: Thirty patients were found to have
      switched to loteprednol etabonate after an increase in IOP during postoperative
      prednisolone acetate treatment. The mean reduction in IOP observed when comparing
      initial and final values in all 30 patients was 12.9 mm Hg during a mean follow
      up of 21.6 weeks. The mean percent reduction in IOP during loteprednol etabonate
      treatment was 32.6% at 3 weeks and 44.9% at 39 weeks. No clinically observed
      signs of allograft rejection were documented. CONCLUSIONS: Switching to
      loteprednol etabonate from prednisolone acetate in known steroid responders was
      successful in reducing IOP and did not increase the risk of allograft rejection.
      Because of its lower potential for causing elevated IOP, loteprednol etabonate
      should be considered in the prophylaxis of allograft rejection in steroid
      responders.

PMID- 19770721
TI  - Evaluation of acute corneal barrier change induced by topically applied
      preservatives using corneal transepithelial electric resistance in vivo.
AB  - PURPOSE: We evaluated acute changes in corneal barrier function after
      instillation with preservatives using corneal transepithelial electric resistance
      (TER) in vivo and cytotoxicity tests in vitro. METHODS: The corneal TER of live
      rabbits was measured using a volt-ohm meter and silver/silver chloride
      electrodes. The cornea was exposed to the preservatives benzalkonium chloride
      (BAC; 0.001%, 0.002%, 0.005%, 0.01%, and 0.02%), 0.04% paraben, 0.5%
      chlorobutanol, 0.005% chlorhexidine digluconate, 2% boric acid, and 0.01%
      ethylenediaminetetraacetic acid, and then changes in the TER were monitored for
      60 seconds. Cultured normal rabbit corneal epithelial cells were exposed to the
      same preservatives for 60 seconds in vitro, and cell viability was evaluated
      using the WST-1 assay. RESULTS: The TER instantly decreased and became
      significantly lower than the control within 10 seconds after instillation with
      0.01% and 0.02% BAC (P < 0.01) and within 60 seconds after that with 0.005% BAC
      (P < 0.01). The TER decreased concomitantly with increasing BAC concentration.
      Cell viability after instillation with 0.005%, 0.01%, and 0.02% BAC for 60
      seconds was significantly lower than that of the control (P < 0.0001). None of
      the other preservatives significantly altered the TER or cell viability.
      Decreases in the TER correlated with cell viability (r = 0.94, P < 0.0001).
      CONCLUSIONS: Instillation with BAC immediately disrupted the corneal epithelium.
      Corneal epithelial cell death is supposed to be associated with a decline in
      barrier function; thus, corneal TER measurement in vivo can assess the acute
      toxicity of preservatives added to ophthalmic drugs.

PMID- 19770722
TI  - Two cases of acanthamoeba keratitis diagnosed only by real-time polymerase chain
      reaction.
AB  - PURPOSE: To report 2 cases of Acanthamoeba keratitis whose causative pathogen was
      detected only by real-time polymerase chain reaction (PCR). METHODS: Histological
      examinations of corneal scrapings were stained with Fungiflora Y. Corneal
      scrapings were also cultured on nonnutrient agar. Real-time PCR analyses of
      corneal scrapings were also performed. RESULTS: Both cases had clinical signs and
      risk factors of Acanthamoeba infection. Histological examinations of corneal
      scrapings with Fungiflora Y staining were negative, and the cultures did not grow
      any pathogens. Real-time PCR analysis was positive for Acanthamoeba DNA from 2
      corneal scrapings. Antiamoebic treatments led to excellent clinical improvements.
      CONCLUSIONS: These results indicate that PCR analyses can detect the DNA of
      Acanthamoeba in corneal scrapings and may be a valuable supplemental examination.
      This method is especially helpful when clinical signs and risk factors of
      Acanthamoeba infection are present but histological examinations with Fungiflora
      Y staining and cultures are negative.

PMID- 19770723
TI  - Endophthalmitis after descemet stripping endothelial keratoplasty with concave
      oriented dislocation on slit-lamp optical coherence topography.
AB  - PURPOSE: To present the first reported case of Descemet membrane stripping
      endothelial keratoplasty (DSEK)-associated endophthalmitis with concave
      dislocation on slit-lamp optical coherence topography (SL-OCT). METHODS: An 86
      year-old man underwent DSEK for corneal decompensation secondary to prior
      surgery. On all postoperative visits, a slit-lamp examination and SL-OCT were
      performed. RESULTS: On the first postoperative day, the lenticle was dislocated
      in a concave configuration as imaged with the SL-OCT. On the second postoperative
      day, the patient had eye pain, nausea, and increased intraocular pressure. On SL
      OCT imaging, the concave configuration and fibrin stranding were imaged. With
      intraocular pressure lowering, the patient's pain subsided, and he was scheduled
      for a lenticle refloat the following day. The next day, endophthalmitis was
      diagnosed secondary to exuberant purulent inflammation. At surgery, the lenticle
      was removed, cultures were obtained, and pars plana vitrectomy and intravitreal
      injections were administered. Intraoperative cultures were positive for heavy
      growth of Streptococcus pneumoniae. CONCLUSIONS: Endophthalmitis is a potential
      complication for any intraocular procedure including DSEK. SL-OCT imaging
      postoperatively may reveal concave lenticle configuration and subtle anterior
      chamber fibrin stranding may be early sign of endophthalmitis.

PMID- 19770724
TI  - Descemetic DALK and predescemetic DALK: outcomes in 236 cases of keratoconus.
AB  - PURPOSE: To report the outcomes of our experience with deep anterior lamellar
      keratoplasty (DALK) in patients with keratoconus. METHODS: A retrospective
      evaluation of 236 eyes of 198 patients that have undergone DALK between 2000 and
      2006 using the Tsubota, Sugita, Melles, or Anwar technique. We analyzed the
      frequency of true Descemet membrane exposure, which we termed dDALK, and the
      number of eyes in which a predescemetic plane was achieved, which we termed
      pdDALK. Pre- and postoperative visual acuity, endothelial cell count, and central
      corneal thickness were evaluated on 120 eyes followed in our department. RESULTS:
      A total of 139 of 236 (59%) eyes were classified as dDALK, with the Anwar
      technique showing the highest incidence of exposure of Descemet's membrane (127
      of 164, 77%). Descemet ruptures occurred in 25 of 236 cases (10.5%). Three
      ruptures were converted to penetrating keratoplasty (PK). There was no difference
      in visual acuity between the pdDALK and dDALK groups at an average follow-up of
      30.4 months, although the eyes in the dDALK group seemed to have faster visual
      recovery. Best spectacle corrected visual acuity postoperatively was at least
      20/30 in 80-85% of eyes at the patient's last visit. Endothelial cell loss was 11
      13%, with most of the loss occurring in the first 6 months. CONCLUSIONS:
      Performing DALK, we had the greatest likelihood of reaching Descemet's membrane
      with the Anwar Big Bubble technique. The visual outcomes are comparable to
      standard PK, avoiding the risk of endothelial rejection. Endothelial cell loss
      was low and the cell count was stable after 6 months.

PMID- 19770725
TI  - Mass spectrometry-based proteomic analyses in contact lens-related dry eye.
AB  - PURPOSE: To identify potential protein biomarkers associated with dry eye in
      contact lens wearers. METHODS: Upon enrollment, current galyfilcon A contact lens
      wearers completed a previously described questionnaire used to classify dry eye
      status. Approximately 5 microL of aqueous tears were carefully sampled from the
      inferior-lateral tear prism of each eye using glass microcapillaries. A variety
      of proteomic approaches were used to compare samples including quantification by
      Bradford analyses, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS
      PAGE) (alone in varying percentages and with MultiPlex analyses for
      posttranslational modifications), nano-liquid chromatography tandem mass
      spectometry (nano-LC-MS/MS), and differential gel electrophoresis. RESULTS:
      Twenty-one subjects were enrolled in the study (age 31.3 +/- 11.6 years). Eleven
      of the subjects were classified with contact lens-related dry eye, while the
      remaining 10 were normal contact lens wearers. Across all proteomic approaches,
      several proteins (including several glycoproteins) were identified as potential
      biomarkers associated with dry eye disease state. In summary across the
      approaches used, extracellular proteins identified to be altered included beta-2
      microglobulin, proline rich 4, lacritin, and secretoglobin 1D1, which were found
      to be decreased in the dry eye state. Secretoglobin 2A2, serum albumin,
      glycoprotein 340, and prolactin-inducible protein were all found to be increased
      in the dry eye state. CONCLUSIONS: Dry eye in contact lens wearers is related to
      several changes in the tear film protein. While functional studies for these
      candidate proteins are ongoing, initial insights into the functions of these
      proteins suggest roles in altered tear secretion, in addition to possible
      increased susceptibility to infection.

PMID- 19770726
TI  - Sutureless amniotic membrane transplantation for severe bacterial keratitis.
AB  - PURPOSE: To evaluate the efficacy of early sutureless amniotic membrane
      transplantation in the management of severe bacterial keratitis to reduce pain,
      inflammation, and haze, and to promote healing. METHOD: A noncomparative case
      series including 3 eyes of 3 consecutive patients with severe bacterial keratitis
      exhibiting persistent epithelial defect/ulcer, more than 5 mm in diameter,
      located within 3mm from the visual axis with infiltration occupying more than 50%
      of the corneal thickness. They were retrospectively reviewed following early (ie,
      within 96 hours) sutureless amniotic membrane transplantation via ProKera
      together with selective topical antibiotics and preservative-free steroid. Pain
      relief, inflammation, haze, and corneal epithelial healing were monitored.
      RESULTS: ProKera was inserted once in 1 eye and twice in the other 2 eyes. Pain
      was significantly relieved and inflammation was markedly reduced in all cases.
      The corneal epithelial defect and stromal ulceration rapidly healed while visual
      acuity improved in 2 of the 3 eyes. CONCLUSION: Temporary sutureless amniotic
      membrane transplantation via ProKera allows easy insertion and replacement of the
      membrane in the office, as well as early intervention to promote
      epithelialization, reduce pain, haze and inflammation in cases with severe
      bacterial keratitis. This result justifies large series controlled studies in the
      future.

PMID- 19770727
TI  - Traumatic wound dehiscence after deep anterior lamellar keratoplasty: protective
      role of intact descemet membrane after big-bubble technique.
AB  - PURPOSE: To describe a case of traumatic wound dehiscence after deep anterior
      lamellar keratoplasty. METHOD: Observational case report. CASE REPORT: A 31-year
      old man who had undergone deep anterior lamellar keratoplasty using big-bubble
      technique for keratoconus 3 months earlier presented to emergency room after
      blunt trauma.On examination, visual acuity was counting fingers at 2 m. The
      corneal graft wound dehisced from 12 to 3 o'clock (90 degrees) with localized
      suture ruptures, but the anterior chamber was deep and the Seidel test was
      negative. Surprisingly, there was intact Descemet membrane prolapsed through the
      corneal wound gap. CONCLUSION: This case indicates that intact Descemet membrane
      remaining after big-bubble technique might reduce the severity of ocular injury
      after traumatic wound dehiscence.

PMID- 19770728
TI  - Migration of limbal melanocytes onto the central cornea after ocular surface
      reconstruction: an in vivo confocal microscopic case report.
AB  - PURPOSE: To report the in vivo confocal microscopic findings of migrated
      melanocytes onto the central cornea in a patient with Stevens-Johnson syndrome
      who received ocular surface reconstruction by amniotic membrane transplantation
      (AMT). METHODS: Single interventional case report. A 37-year-old man presented
      with bilateral symblepharon because of Stevens-Johnson syndrome. Release of the
      bilateral symblepharon with AMT on the bare sclera was performed. RESULTS: Three
      weeks after the surgery, slit-lamp biomicroscopy of the right eye revealed patchy
      brown pigmentation on the surface of the cornea and the amniotic membrane
      transplanted to the bare sclera. In vivo confocal microscopy of the affected
      cornea revealed abnormal basal epithelial cells with hyperreflective nuclei and
      loss of cellular borders. Multiple dendritiform cells, which appeared to be
      melanocytes, were distributed mainly on the corneal basal epithelial layer and
      superficial stroma. The number of the migrated melanocytes gradually decreased
      over 6 months of observation. CONCLUSIONS: Melanocytes can migrate into the
      central cornea after reconstruction of the ocular surface with AMT. In vivo
      confocal microscopy can be a useful tool to observe these changes.

PMID- 19770729
TI  - Penetrating keratoplasty for invasive fungal keratitis resulting from a thorn
      injury involving Phomopsis species.
AB  - PURPOSE: The purpose of this study was to report a case of Phomopsis fungal
      keratitis that was diagnosed 2 months after a rose thorn injury that occurred
      while gardening. METHODS: The authors conducted a retrospective case report with
      literature review. RESULTS: Deep stromal keratitis with extension of hyphae
      through Descemet's membrane was treated by therapeutic keratoplasty combined with
      oral and topical antifungal medications. The causative organism, a Phomopsis
      species, was identified by culture of the surgical specimens. Phomopsis, a plant
      fungus, has not been previously reported as a cause of human fungal keratitis.
      One year after the initial surgery, visual rehabilitation was accomplished with a
      repeat cornea transplant and cataract extraction with return of vision to 20/25.
      CONCLUSIONS: Advanced fungal keratitis can be successfully treated by a
      combination of surgery to debulk the infectious organisms and pre- and
      postoperative medical therapy. Prompt recognition of fungal keratitis will
      increase the likelihood of cure. Phomopsis species, ubiquitous plant fungi, can
      cause infectious keratitis in humans.

PMID- 19770730
TI  - Delayed, bilateral descemet's membrane detachments with spontaneous resolution:
      Implications for nonsurgical treatment.
AB  - PURPOSE: To report a case of delayed bilateral Descemet's detachment with
      spontaneous resolution in one eye following successful treatment of the fellow
      eye. METHOD: Case report. RESULTS: A 78-year-old male who underwent uncomplicated
      bilateral cataract extraction with phacoemulsification developed delayed
      bilateral Descemet's membrane detachments. One eye was successfully treated with
      pneumatic descemetopexy. After appropriate positioning for the surgical eye, the
      fellow eye simultaneously and spontaneously resolved. CONCLUSIONS: Spontaneous
      resolution of delayed Descemet's membrane detachments can occur. We suggest a
      mechanism for spontaneous resolution that may have implications for nonsurgical
      treatment.

PMID- 19770731
TI  - Bilateral acanthamoeba keratitis after orthokeratology.
AB  - PURPOSE: To report bilateral Acanthamoeba keratitis after wearing an overnight
      reverse geometry contact lens for 5 days. METHODS: Case report and review of the
      medical literature. RESULTS: A 22-year-old woman developed bilateral corneal
      ulcers during orthokeratology. A slit-lamp examination revealed round epithelial
      abrasion, radial infiltration, and disciform keratitis in both corneas. Visual
      acuity in her right eye (OD) was hand motion and left eye (OS) was counting
      fingers. Bilateral Acanthamoeba keratitis was diagnosed by culture using
      nonnutrient agar overlaid with viable Escherichia coli. Small, round, and double
      walled cysts were observed in nonnutrient agar under an inverted phase contrast
      microscope. Topical 0.02% polyhexamethylene biguanide, Cravit (0.5%
      levofloxacin), and Tobra (0.5% tobramycin) were administered. After 1 month of
      treatment, the corneal ulcers had healed and the patient's best-corrected visual
      acuity was 20/100 OD and 20/25 OS. CONCLUSIONS: Acanthamoeba keratitis can
      simultaneously affect both eyes during overnight orthokeratology.

PMID- 19770732
TI  - Hypertonic saline alters hydraulic conductivity and up-regulates
      mucosal/submucosal aquaporin 4 in resuscitation-induced intestinal edema.
AB  - OBJECTIVE: To characterize membrane conductivity by applying mathematical
      modeling techniques and immunohistochemistry and to localize and predict areas of
      the bowel where aquaporins may be associated with edema resolution/prevention
      associated with hypertonic saline. Intestinal edema induced by resuscitation and
      mesenteric venous hypertension impairs intestinal transit/contractility.
      Hypertonic saline decreases intestinal edema and improves transit. Aquaporins are
      water transport membrane proteins that may be up-regulated with edema and/or
      hypertonic saline. DESIGN: Laboratory study. SETTING: University research
      laboratory. SUBJECTS: Male Sprague Dawley rats, weighing 270 to 330 g.
      INTERVENTIONS: Rats were randomized to control (with and without hypertonic
      saline) and mesenteric venous hypertension with either 80 mL/kg normal saline
      (RESUS + VH + VEH) or 80 mL/kg normal saline with hypertonic saline (RESUS + VH +
      HTS). After 6 hrs, intestinal wet/dry ratios, urine output, peritoneal fluid, and
      intraluminal fluid were measured. Hydraulic conductivity was calculated from our
      previously known and published pressure-flow data. The cDNA microarray, Western
      blot, polymerase chain reaction, and immunohistochemistry studies were conducted
      for candidate aquaporins and distribution in intestinal edema resolution.
      MEASUREMENTS AND MAIN RESULTS: Hypertonic saline decreased edema and increased
      urine, intraluminal, and peritoneal fluid volume. RESUS + VH favors fluid flux
      into the interstitium. Hypertonic saline causes increased hydraulic conductivity
      at the seromuscular and mucosal surfaces at the same time limiting flow into the
      interstitium. This is associated with increased aquaporin 4 expression in the
      intestinal mucosa and submucosa. CONCLUSIONS: Hypertonic saline mitigates
      intestinal edema development and promotes fluid redistribution secondary to
      increased membrane conductivity at the mucosal and seromuscular surfaces. This is
      associated with up-regulation of aquaporin 4 gene expression and protein.
      Aquaporin 4 may be a useful therapeutic target for strategies to enhance edema
      resolution.

PMID- 19770733
TI  - Expectations and outcomes of prolonged mechanical ventilation.
AB  - OBJECTIVE: To compare prolonged mechanical ventilation decision-makers'
      expectations for long-term patient outcomes with prospectively observed outcomes
      and to characterize important elements of the surrogate-physician interaction
      surrounding prolonged mechanical ventilation provision. Prolonged mechanical
      ventilation provision is increasing markedly despite poor patient outcomes.
      Misunderstanding prognosis in the prolonged mechanical ventilation decision
      making process could provide an explanation for this phenomenon. DESIGN:
      Prospective observational cohort study. SETTING: Academic medical center.
      PATIENTS: A total of 126 patients receiving prolonged mechanical ventilation.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Participants were interviewed
      at the time of tracheostomy placement about their expectations for 1-yr patient
      survival, functional status, and quality of life. These expectations were then
      compared with observed 1-yr outcomes measured with validated questionnaires. The
      1-yr follow-up was 100%, with the exception of patient death or cognitive
      inability to complete interviews. At 1 yr, only 11 patients (9%) were alive and
      independent of major functional status limitations. Most surrogates reported high
      baseline expectations for 1-yr patient survival (n = 117, 93%), functional status
      (n = 90, 71%), and quality of life (n = 105, 83%). In contrast, fewer physicians
      described high expectations for survival (n = 54, 43%), functional status (n = 7,
      6%), and quality of life (n = 5, 4%). Surrogate-physician pair concordance in
      expectations was poor (all kappa = <0.08), as was their accuracy in outcome
      prediction (range = 23%-44%). Just 33 surrogates (26%) reported that physicians
      discussed what to expect for patients' likely future survival, general health,
      and caregiving needs. CONCLUSIONS: One-year patient outcomes for prolonged
      mechanical ventilation patients were significantly worse than expected by
      patients' surrogates and physicians. Lack of prognostication about outcomes,
      discordance between surrogates and physicians about potential outcomes, and
      surrogates' unreasonably optimistic expectations seem to be potentially
      modifiable deficiencies in surrogate-physician interactions.

PMID- 19770734
TI  - Variation in cerebral blood flow velocity with cerebral perfusion pressure >40 mm
      Hg in 42 children with severe traumatic brain injury.
AB  - OBJECTIVE: : To determine the prevalence of low, normal, and high mean middle
      cerebral artery flow velocity when cerebral perfusion pressure is >40 mm Hg in
      children with severe traumatic brain injury. There is no information regarding
      the relationship between middle cerebral artery flow velocity and cerebral
      perfusion pressure in pediatric traumatic brain injury. DESIGN: : Prospective,
      observational study. SETTING: : Level I pediatric trauma center. PATIENTS: : A
      total of 42 children <17 yrs of age with an admission diagnosis of severe
      traumatic brain injury (admission Glasgow Coma Scale score of <9), traumatic
      brain injury on computed tomography scan, tracheal intubation/mechanical
      ventilation, and intracranial pressure monitoring. INTERVENTIONS: : None.
      MEASUREMENTS AND MAIN RESULTS: : Bilateral middle cerebral arteries were
      insonated using transcranial Doppler ultrasonography to calculate mean middle
      cerebral artery flow velocity after traumatic brain injury. Low mean middle
      cerebral artery flow velocity was defined as middle cerebral artery flow velocity
      <2 standard deviation and high was defined as mean middle cerebral artery flow
      velocity >2 standard deviation. Patients were grouped by age (0.8-2.9, 3-5.9, 6
      9.9, and 10-16.9 yrs) and gender to examine the relationship between cerebral
      perfusion pressure and low, high, or normal mean middle cerebral artery flow
      velocity. Potential confounders of the relationship between cerebral perfusion
      pressure and mean middle cerebral artery flow velocity (intracranial pressure,
      PaCO2, hematocrit, sedation, fever,and impaired autoregulation were examined).
      Most children (n = 33; 79%) had normal mean middle cerebral artery flow velocity
      but four patients (9%) had low mean middle cerebral artery flow velocity and five
      children (12%) had high mean middle cerebral artery flow velocity despite
      cerebral perfusion pressure >40 mm Hg. There was no difference in potential
      confounders of the relationship between cerebral perfusion pressure and mean
      middle cerebral artery flow velocity except for hematocrit, which was lower (25
      +/- 4%; range = 21-30%) in children with high mean middle cerebral artery flow
      velocity. An inverse relationship between mean middle cerebral artery flow
      velocity and hematocrit was also found in boys aged 10 to 16.9 yrs. CONCLUSIONS:
      : Both low and/or high mean middle cerebral artery flow velocity occur with
      cerebral perfusion pressure >40 mm Hg in severe pediatric traumatic brain injury.
      Of the potential confounders considered, only lower hematocrit was associated
      with high mean middle cerebral artery flow velocity.

PMID- 19770735
TI  - Identification of patient information corruption in the intensive care unit:
      using a scoring tool to direct quality improvements in handover.
AB  - OBJECTIVE: To use a handover assessment tool for identifying patient information
      corruption and objectively evaluating interventions designed to reduce handover
      errors and improve medical decision making. The continuous monitoring,
      intervention, and evaluation of the patient in modern intensive care unit
      practice generates large quantities of information, the platform on which medical
      decisions are made. Information corruption, defined as errors of
      distortion/omission compared with the medical record, may result in medical
      judgment errors. Identifying these errors may lead to quality improvements in
      intensive care unit care delivery and safety. DESIGN: Handover assessment
      instrument development study divided into two phases by the introduction of a
      handover intervention. SETTING: Closed, 17-bed, university-affiliated mixed
      surgical/medical intensive care unit. SUBJECTS: Senior and junior medical members
      of the intensive care unit team. INTERVENTIONS: Electronic handover page.
      MEASUREMENTS AND MAIN RESULTS: Study subjects were asked to recall clinical
      information commonly discussed at handover on individual patients. The handover
      score measured the percentage of information correctly retained for each
      individual doctor-patient interaction. The clinical intention score, a subjective
      measure of medical judgment, was graded (1-5) by three blinded intensive care
      unit experts. A total of 137 interactions were scored. Median (interquartile
      range) handover scores for phases 1 and 2 were 79.07% (67.44-84.50) and 83.72%
      (76.16-88.37), respectively. Score variance was reduced by the handover
      intervention (p < .05). Increasing median handover scores, 68.60 to 83.72, were
      associated with increases in clinical intention scores from 1 to 5 (chi-square =
      23.59, df = 4, p < .0001). CONCLUSIONS: When asked to recall clinical information
      discussed at handover, medical members of the intensive care unit team provide
      data that are significantly corrupted compared with the medical record. Low
      subjective clinical judgment scores are significant associated with low handover
      scores. The handover/clinical intention scores may, therefore, be useful
      screening tools for intensive care unit system vulnerability to medical error.
      Additionally, handover instruments can identify interventions that reduce system
      vulnerability to error and may be used to guide quality improvements in handover
      practice.

PMID- 19770736
TI  - Antihypertensive treatment of acute cerebral hemorrhage.
AB  - OBJECTIVE: To determine the feasibility and acute (i.e., within 72 hrs) safety of
      three levels of systolic blood pressure reduction in subjects with supratentorial
      intracerebral hemorrhage treated within 6 hrs after symptom onset. DESIGN: A
      traditional phase I, dose-escalation, multicenter prospective study. SETTINGS:
      Emergency departments and intensive care units. PATIENTS: Patients with
      intracerebral hemorrhage with elevated systolic blood pressure > or = 170 mm Hg
      who present to the emergency department within 6 hrs of symptom onset.
      INTERVENTION: Intravenous nicardipine to reduce systolic blood pressure to a
      target of: (1) 170 to 200 mm Hg in the first cohort of patients; (2) 140 to 170
      mm Hg in the second cohort; and (3) 110 to 140 mm Hg in the third cohort.
      MEASUREMENTS AND MAIN RESULTS: Primary outcomes of interest were: (1) treatment
      feasibility (achieving and maintaining the systolic blood pressure goals for 18
      24 hrs); (2) neurologic deterioration within 24 hrs; and (3) serious adverse
      events within 72 hrs. Safety stopping rules based on neurologic deterioration and
      serious adverse events were prespecified and approved by an NIH-appointed Data
      and Safety Monitoring Board, which provided oversight on subject safety. Each
      subject was followed-up for 3 months to preliminarily assess mortality and the
      clinical outcomes. A total of 18, 20, and 22 patients were enrolled in the
      respective three tiers of systolic blood pressure treatment goals. Overall, 9 of
      60 patients had treatment failures (all in the last tier). A total of seven
      subjects with neurologic deterioration were observed: one (6%), two (10%), and
      four (18%) in tier one, two, and three, respectively. Serious adverse events were
      observed in one subject (5%) in tier two and in three subjects (14%) in tier
      three. However, the safety stopping rule was not activated in any of the tiers.
      Three (17%), two (10%), and five (23%) subjects in tiers one, two, and three,
      respectively, died within 3 months. CONCLUSIONS: The observed proportions of
      neurologic deterioration and serious adverse events were below the prespecified
      safety thresholds, and the 3-month mortality rate was lower than expected in all
      systolic blood pressure tiers. The results form the basis of a larger randomized
      trial addressing the efficacy of systolic blood pressure reduction in patients
      with intracerebral hemorrhage.

PMID- 19770737
TI  - Immortal time bias in critical care research: application of time-varying Cox
      regression for observational cohort studies.
AB  - OBJECTIVES: To examine the bias introduced by using time-fixed methodology to
      analyze the effects of a time-varying exposure incurred in the intensive care
      unit. DESIGN: Prospective cohort and Monte Carlo simulation studies. SETTING:
      Medical and coronary intensive care units in a university hospital. PATIENTS: A
      total of 224 mechanically ventilated patients. METHODS: Part I was a case study
      analyzing the association between delirium in the intensive care unit (exposure
      variable) and outcomes (intensive care unit length of stay and 6-mo mortality) in
      a prospective cohort study. Part II was a Monte Carlo simulation generating
      16,000 data sets wherein the true associations between delirium and outcomes were
      known before analysis. In both parts, we assessed associations between delirium
      in the intensive care unit and outcomes (intensive care unit length of stay and
      mortality), using time-fixed vs. time-varying Cox regression methodology.
      MEASUREMENTS AND MAIN RESULTS: In the case study, delirium analyzed as a time
      fixed variable was associated with a delayed intensive care unit discharge
      (adjusted hazard ratio = 1.9, 95% confidence interval, 1.3-2.7, p < .001), but no
      association was noted using a time-varying method (adjusted hazard ratio = 1.1,
      95% confidence interval = 0.7-1.6, p = .70). Alternatively, delirium analyzed as
      a time-fixed variable was not associated with 6-mo mortality (adjusted hazard
      ratio = 2.9, 95% confidence interval, 0.9-5.0, p = .09), whereas delirium
      analyzed as a time-varying variable was associated with increased mortality
      (adjusted hazard ratio = 3.2, 95% confidence interval, 1.4-7.7, p = .008). In the
      simulation study, time-fixed methods produced erroneous results in 97.1% of the
      data sets with no true association; time-varying methods produced erroneous
      results in only 3.7%. Similarly, time-fixed methods produced biased results when
      a true association was present, whereas time-varying methods produced accurate
      results. CONCLUSIONS: Studies using a time-fixed analytic approach to understand
      relationships between exposures and clinical outcomes can result in considerable
      bias when the variables overlap temporally in occurrence. Those conducting such
      studies, and clinicians reading them, should ensure that time-varying exposures
      are correctly analyzed to avoid biased conclusions.

PMID- 19770738
TI  - Active surface cooling protocol to induce mild therapeutic hypothermia after out
      of-hospital cardiac arrest: a retrospective before-and-after comparison in a
      single hospital.
AB  - OBJECTIVE: To evaluate whether implementation of a therapeutic hypothermia
      protocol on arrival in a community hospital improved survival and neurologic
      outcomes in patients initially found to have ventricular fibrillation, pulseless
      electrical activity, or asystole, and then successfully resuscitated from out-of
      hospital cardiac arrest. DESIGN: A retrospective study of patients who presented
      after implementation of a therapeutic hypothermia protocol compared with those
      who presented before the protocol was implemented. SETTING: Harborview Medical
      Center, Seattle, WA. PATIENTS: A total of 491 consecutive adults with out-of
      hospital, nontraumatic cardiac arrest who presented between January 1, 2000 and
      December 31, 2004. INTERVENTIONS: An active cooling therapeutic hypothermia
      protocol, using ice packs, cooling blankets, or cooling pads to achieve a
      temperature of 32 degrees C to 34 degrees C was initiated on November 18, 2002
      for unconscious patients resuscitated from cardiac arrest. MEASUREMENTS AND MAIN
      RESULTS: Demographics and outcomes were obtained from medical records and an
      emergency medical database. The primary outcomes were survival and favorable
      neurologic outcome at discharge associated with the therapeutic hypothermia
      protocol. An adjusted analysis was performed, using a multivariate regression.
      During the therapeutic hypothermia period, 204 patients were brought to the
      emergency department; of these 204 patients, 132 (65%) ultimately achieved
      temperatures of <34 degrees C. Of the 72 patients who did not achieve goal
      temperatures: 40 (20%) died in the emergency department or shortly after being
      admitted to the hospital, 15 (7%) regained consciousness, four (2%) had
      contraindications, 13 (6%) had temperature increase or did not have documented
      use of the therapeutic hypothermia protocol. In the prior period, none of the 287
      patients received active cooling. Patients admitted in the therapeutic
      hypothermia period had a mean esophageal temperature of 34.1 degrees C during the
      first 12 hrs compared with 35.2 degrees C in the pretherapeutic hypothermia
      period (p < .01). Survival to hospital discharge improved in the therapeutic
      hypothermia period in patients with an initial rhythm of ventricular fibrillation
      (odds ratio, 1.88, 95% confidence interval, 1.03-3.45), however not in patients
      with nonventricular fibrillation (odds ratio, 1.17, 95% confidence interval, 0.66
      2.05). In adjusted analysis, ventricular fibrillation patients during the
      therapeutic hypothermia period trended toward improved survival (odds ratio,
      1.71, 95% confidence interval, 0.85-3.46) and had favorable neurologic outcome
      (odds ratio, 2.62, 95% confidence interval, 1.1-6.27) compared with the earlier
      period. This benefit was not observed in patients whose initial rhythm was
      pulseless electrical activity or asystole. CONCLUSIONS: The therapeutic
      hypothermia period was associated with a significant improvement in neurologic
      outcomes in patients whose initial rhythm was ventricular fibrillation, but not
      in patients with other rhythms.

PMID- 19770739
TI  - Intra-aortic balloon counterpulsation in patients with acute myocardial
      infarction complicated by cardiogenic shock: the prospective, randomized IABP
      SHOCK Trial for attenuation of multiorgan dysfunction syndrome.
AB  - OBJECTIVE: Patients undergoing percutaneous coronary intervention (PCI) for acute
      myocardial infarction with cardiogenic shock (CS) are often treated with intra
      aortic balloon pump counterpulsation (IABP), even though the evidence to support
      this is limited. We determined whether IABP as an addition to PCI-centered
      therapy ameliorates multiorgan dysfunction syndrome (MODS) in patients with acute
      myocardial infarction complicated by CS. DESIGN: A prospective, randomized,
      controlled, open-label clinical trial recruiting patients between March 2003 and
      June 2004 (ClinicalTrials.gov ID NCT00469248). SETTING: Tertiary care university
      hospital. PATIENTS AND INTERVENTIONS: Forty-five consecutive patients with AMI
      and CS undergoing PCI were randomized to treatment with or without IABP.
      MEASUREMENTS AND MAIN RESULTS: Acute Physiology and Chronic Health Evaluation
      (APACHE) II scores (primary outcome measure), hemodynamic values, inflammatory
      markers, and plasma brain natriuretic peptide (BNP) levels (secondary outcomes)
      were collected over 4 days from randomization. The prospective hypothesis was
      that adding IABP therapy to "standard care" would improve CS-triggered MODS. The
      addition of IABP to standard therapy did not result in a significant improvement
      in MODS (measured by serial APACHE II scoring over 4 days). IABP use had no
      significant effect on cardiac index or systemic inflammatory activation, although
      BNP levels were significantly lower in IABP-treated patients. Initial and serial
      APACHE II scoring correlated with mortality better than cardiac index, systemic
      inflammatory state, and BNP levels in this group of patients. Nonsurvivors had
      significantly higher initial APACHE II scores (29.9 +/- 2.88) than survivors
      (18.1 +/- 1.66, p < .05). Nevertheless, discrepancies among patients within the
      groups cannot be ruled out and might interfere with our results. CONCLUSIONS: In
      this randomized trial addressing addition of IABP in CS patients, mechanical
      support was associated only with modest effects on reduction of APACHE II score
      as a marker of severity of disease, improvement of cardiac index, reduction of
      inflammatory state, or reduction of BNP biomarker status compared with medical
      therapy alone. However, the limitations of our present trial preclude any
      definitive conclusion, but request for a larger prospective, randomized,
      multicentered trial with mortality as primary end point.

PMID- 19770741
TI  - Rhythms and outcomes of adult in-hospital cardiac arrest.
AB  - OBJECTIVE: To determine the relationship of electrocardiographic rhythm during
      cardiac arrest with survival outcomes. DESIGN: Prospective, observational study.
      SETTING: Total of 411 hospitals in the National Registry of Cardiopulmonary
      Resuscitation. PATIENTS: Total of 51,919 adult patients with pulseless cardiac
      arrests from April 1999 to July 2005. MEASUREMENTS AND MAIN RESULTS: Registry
      data collected included first documented rhythm, patient demographics, pre-event
      data, event data, and survival and neurologic outcome data. Of 51,919 indexed
      cardiac arrests, first documented pulseless rhythm was ventricular tachycardia
      (VT) in 3810 (7%), ventricular fibrillation (VF) in 8718 (17%), pulseless
      electrical activity (PEA) in 19,262 (37%) and asystole 20,129 (39%). Subsequent
      VT/VF (that is, VT or VF occurring during resuscitation for PEA or asystole)
      occurred in 5154 (27%), with first documented rhythm of PEA and 4988 (25%) with
      asystole. Survival to hospital discharge rate was not different between those
      with first documented VF and VT (37% each, adjusted odds ratio [OR]) 1.08; 95%
      confidence interval [CI] 0.95-1.23). Survival to hospital discharge was slightly
      more likely after PEA than asystole (12% vs. 11%, adjusted OR 1.1; 95% CI 1.00
      1.18), Survival to discharge was substantially more likely after first documented
      VT/VF than PEA/asystole (adjusted OR 1.68; 95% CI 1.55-1.82). Survival to
      discharge was also more likely after PEA/asystole without subsequent VT/VF
      compared with PEA/asystole with subsequent VT/VF (14% vs. 7% for PEA without vs.
      with subsequent VT/VF; 12% vs. 8% for asystole without vs. with subsequent VT/VF;
      adjusted OR 1.60; 95% CI, 1.44-1.80). CONCLUSIONS: Survival to hospital discharge
      was substantially more likely when the first documented rhythm was shockable
      rather than nonshockable, and slightly more likely after PEA than asystole.
      Survival to hospital discharge was less likely following PEA/asystole with
      subsequent VT/VF compared to PEA/asystole without subsequent VT/VF.

PMID- 19770740
TI  - Streptococcus pneumoniae and Pseudomonas aeruginosa pneumonia induce distinct
      host responses.
AB  - OBJECTIVE: Pathogens that cause pneumonia may be treated in a targeted fashion by
      antibiotics, but if this therapy fails, then treatment involves only nonspecific
      supportive measures, independent of the inciting infection. The purpose of this
      study was to determine whether host response is similar after disparate
      infections with similar mortalities. DESIGN: Prospective, randomized controlled
      study. SETTING: Animal laboratory in a university medical center. INTERVENTIONS:
      Pneumonia was induced in FVB/N mice by either Streptococcus pneumoniae or two
      different concentrations of Pseudomonas aeruginosa. Plasma and bronchoalveolar
      lavage fluid from septic animals was assayed by a microarray immunoassay
      measuring 18 inflammatory mediators at multiple time points. MEASUREMENTS AND
      MAIN RESULTS: The host response was dependent on the causative organism as well
      as kinetics of mortality, but the pro-inflammatory and anti-inflammatory
      responses were independent of inoculum concentration or degree of bacteremia.
      Pneumonia caused by different concentrations of the same bacteria, Pseudomonas
      aeruginosa, also yielded distinct inflammatory responses; however, inflammatory
      mediator expression did not directly track the severity of infection. For all
      infections, the host response was compartmentalized, with markedly different
      concentrations of inflammatory mediators in the systemic circulation and the
      lungs. Hierarchical clustering analysis resulted in the identification of five
      distinct clusters of the host response to bacterial infection. Principal
      components analysis correlated pulmonary macrophage inflammatory peptide-2 and
      interleukin-10 with progression of infection, whereas elevated plasma tumor
      necrosis factor sr2 and macrophage chemotactic peptide-1 were indicative of
      fulminant disease with >90% mortality within 48 hrs. CONCLUSIONS: Septic mice
      have distinct local and systemic responses to Streptococcus pneumoniae and
      Pseudomonas aeruginosa pneumonia. Targeting specific host inflammatory responses
      induced by distinct bacterial infections could represent a potential therapeutic
      approach in the treatment of sepsis.

PMID- 19770742
TI  - Insulin increases resistance to burn wound infection-associated sepsis.
AB  - OBJECTIVE: This study was designed to determine the ability of insulin to improve
      outcome following a Pseudomonas aeruginosa wound infection in a rodent model of
      severe burn injury. BACKGROUND: Severe burn injury predisposes patients to burn
      wound infections that can disseminate, lead to uncontrolled inflammation, and
      induce septic shock. Whereas insulin administration has been extensively
      discussed to improve morbidity and mortality in critically ill patients, the
      ability of insulin to improve outcomes of severely burned patients with infected
      burn wounds is not known. DESIGN: Sprague-Dawley rats. SETTING: University
      setting. INTERVENTION: Burn-injured Sprague Dawley rats were randomized into
      treatment groups that received either saline or insulin. Burn wounds were
      topically inoculated with a lethal dose of Pseudomonas aeruginosa 6 days after
      injury. MEASUREMENTS AND MAIN RESULTS: Survival, systemic dissemination of
      bacteria, systemic inflammation, and immune activation were examined. Insulin
      decreased the early inflammatory response to a severe burn injury. Treatment with
      low doses of insulin following burn injury improved the outcome of rats in
      response to a lethal burn wound infection. Specifically, survival was improved
      and systemic dissemination of bacteria from the wound was decreased. Systemic
      inflammation, indicated by serum interleukin-6 levels, was significantly
      decreased by insulin treatments after injury. Additionally, insulin treatments
      were associated with alterations in B and T lymphocyte responses to wound
      infection. CONCLUSIONS: Although the mechanisms by which insulin improves outcome
      following a lethal burn wound infection are not known, the data suggest that
      immunologic responses to infection may be altered by postburn insulin treatments.

PMID- 19770743
TI  - Is there an association between nosocomial infection rates and bacterial cross
      transmissions?
AB  - OBJECTIVE: Surveillance data of nosocomial infection rates are increasingly used
      for public reporting and interhospital comparisons. Approximately 15% of
      nosocomial infections on intensive care units are the result of patient-to
      patient transmissions of the causative organisms. These exogenous infections
      could be prevented by adherence to basic infection control measures. The
      association between bacterial cross transmissions and nosocomial infection rates
      was analyzed. DESIGN: Prospective cohort study during 24 months. SETTING: Eleven
      intensive care units from two university hospitals. PATIENTS: All inpatients.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary isolates of six
      indicator organisms (Acinetobacter baumannii, Enterococcus faecalis and E.
      faecium, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus)
      cultured from clinical samples or methicillin-resistant S. aureus surveillance
      testing of all inpatients were genotyped. Indistinguishable isolates in > or =2
      patients defined potential episodes of transmissions. Surveillance of nosocomial
      infection rates was performed according to the German nosocomial infection
      surveillance system, Krankenhaus Infektions Surveillance System. Transmission
      events and nosocomial infection rates were pooled by intensive care unit to
      calculate Spearman's rank-correlation test. During 100,781 patient days, 100,829
      microbiological specimens from 24,362 patients were sampled (average
      investigation density: 1.0 sample per patient and day) and 3419 primary indicator
      organisms were cultured. Altogether, 462 transmissions (incidence density of 4.6
      transmissions per 1000 patient days; range, 1.4-8.4 days) and 1216 nosocomial
      infections (incidence density of 12.1 per 1000 patient days; range, 6.2-16.6
      days) were discerned. Correlation analysis was unable to reveal any association
      between the incidence of cross transmissions and nosocomial infections, duration
      of hospitalization, or device use. CONCLUSIONS: Differences in nosocomial
      infection rates between study intensive care units are not explained solely by
      cross transmissions. Other factors, like the severity of the patient's underlying
      diseases, the patient's endogenous flora, or invasive procedures, likely have a
      dominant effect on the magnitude of nosocomial infection rates.

PMID- 19770744
TI  - Bacteremia, acute physiology and chronic health evaluation II and modified end
      stage liver disease are independent predictors of mortality in critically ill
      nontransplanted patients with acute on chronic liver failure.
AB  - OBJECTIVES: To determine what physiological and biochemical factors predict
      development of bacteremia in nontransplanted patients with acute on chronic liver
      failure and, on diagnosis of bacteremia, what is the natural history of
      bacteremic patients versus control subjects (acute on chronic liver failure).
      INTERVENTIONS: None. DESIGN: Retrospective analysis of data collected
      prospectively and entered into a dedicated physiology database. SETTING:
      Specialist liver intensive therapy unit. PATIENTS: Critically ill non
      transplanted patients with acute on chronic liver failure admitted between
      January 2003 and July 2005. MEASUREMENTS AND MAIN RESULTS: One hundred eighty
      four patients were defined with acute on chronic liver failure; 67 (36%) had
      bacteremia. One hundred seventeen (64%) patients did not (acute on chronic liver
      failure). Fifty-eight percent of isolates were Gram-negative organisms, 36% were
      Gram-positives, and 6% fungemia. Median time to first bacteremia was 8 days
      (range, 3-12 days). On admission (univariate), bacteremic patients had
      significantly higher Modified End Stage Liver Disease scores (27 vs. 24, p =
      .037), Acute Physiology and Chronic Health Evaluation II scores (23 vs. 21, p =
      .049), and greater degrees of encephalopathy (Glasgow Coma Scale score 10 vs. 12,
      p = .001). During their liver intensive therapy unit course, bacteremic patients
      had significantly greater requirements for renal replacement therapy (64% vs.
      49%, p = .043), mechanical ventilation (88% vs. 68%, p = .002), and a longer
      median liver intensive therapy unit stay (16 vs. 5 days, p < .001). Survival to
      hospital discharge was worse in the bacteremic group (25% vs. 56%, p < .001).
      Multivariate analysis (logistic regression) was performed separately modeling
      with Acute Physiology and Chronic Health Evaluation II and Modified End Stage
      Liver Disease. In the first model, Acute Physiology and Chronic Health Evaluation
      II (odds ratio 1.24) and bacteremia (2.24) were independent predictors of
      mortality. In the later model, Modified End Stage Liver Disease (odds ratio,
      1.06), requirement for renal replacement therapy (3.08), Glasgow Coma Scale
      (0.72), and bacteremia (2.30) were significant. Both models performed similarly
      (Modified End Stage Liver Disease area under the receiver operating
      characteristic curve, 0.864; Acute Physiology and Chronic Health Evaluation II,
      0.862). CONCLUSIONS: In nontransplanted patients with acute on chronic liver
      failure, bacteremia was associated with increased severity of illness on
      admission, greater requirements for organ support, and independently adversely
      impacted on survival. Higher Acute Physiology and Chronic Health Evaluation II
      and Modified End Stage Liver Disease scores were also independently predictive of
      mortality.

PMID- 19770745
TI  - Gene expression profiling: classification of mice with left ventricle systolic
      dysfunction using microarray analysis.
AB  - OBJECTIVE: We tested the hypothesis that a set of differentially expressed genes
      could be used to classify mice according to cardiovascular phenotype after
      prolonged catecholamine stress. DESIGN: Prospective, randomized study. SETTING:
      University-based research laboratory. SUBJECTS: One hundred seventy-three male
      mice were studied: wild-type (WT) C57, WT FVB, WT B6129SF2/J, and beta2
      adrenergic receptor knockout. INTERVENTIONS: Mice of each genotype were randomly
      assigned to 14-day infusions of isoproterenol (120 microg/g/day) or no treatment.
      Approximately half of the animals underwent left ventricle pressure volume loop
      analysis. The remaining animals were killed for extraction of messenger RNA from
      whole heart preparations for microarray analysis. MEASUREMENTS AND MAIN RESULTS:
      We observed that WT FVB and beta2 adrenergic receptor knockout mice developed
      systolic dysfunction in response to continuous catecholamine infusion, whereas WT
      C57 mice developed diastolic dysfunction. Using these mice as the derivation
      cohort, we identified a set of 83 genes whose differential expression correlated
      with left ventricle systolic dysfunction. The gene set was then used to
      accurately classify mice from a separate group (WT B6129SF2/J) into the cohort
      that developed left ventricle systolic dysfunction after catecholamine stress.
      CONCLUSIONS: The differential expression pattern of 83 genes can be used to
      accurately classify mice according to physiological phenotype after catecholamine
      stress.

PMID- 19770746
TI  - Antiplatelet drugs and outcome in mixed admissions to an intensive care unit.
AB  - OBJECTIVE: Platelet activation has been implicated in microvascular thrombosis
      and organ failure. We tested the hypothesis that antiplatelet drugs favorably
      affect outcome in patients nonelectively admitted to an intensive care unit.
      DESIGN: Retrospective cohort study. SETTING: A 22-bed intensive care unit of a
      tertiary care center. PATIENTS: Six hundred fifteen consecutive patients admitted
      to an intensive care unit within 24 hrs after hospitalization were enrolled,
      approximately 25% of whom received antiplatelet drugs (acetylsalicylic acid,
      clopidogrel) for secondary prevention of vascular disease. Impact of antiplatelet
      drugs and established risk factors on mortality were assessed by logistic
      regression and 2 x 2 table analysis. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: Patients on antiplatelet drugs were markedly older and presented higher
      Acute Physiology and Chronic Health Evaluation II scores on intensive care unit
      admission. There was no significant difference in injury severity scores in
      trauma patients with (21 [range, 13-29]) or without antiplatelet drugs (18
      [range, 12-29]). Using logistic regression analysis, a significant reduction of
      mortality was estimated for the use of antiplatelet drugs in various subgroups of
      patients with normal or high bleeding risk (odds ratios, 0.04-0.34). Significant
      benefit was also estimated by 2 x 2 table analysis of Acute Physiology and
      Chronic Health Evaluation II-matched samples (Acute Physiology and Chronic Health
      Evaluation II >20) of internal medicine patients and/or patients receiving
      medical treatment. No significant benefit but also no harm of antiplatelet drugs
      was estimated in Acute Physiology and Chronic Health Evaluation II-matched
      samples of patients with increased bleeding risk: patients from surgery
      departments overall, patients with surgical treatment, trauma, active bleeding,
      or transfusion (odds ratios, 0.51-0.88). CONCLUSIONS: Our data are consistent
      with prevention of organ dysfunction by antiplatelet drugs, which may be masked
      in some patients by concomitant bleeding risk. Antiplatelet drugs might offer a
      novel therapeutic option to prevent organ failure, at least in the absence of
      active bleeding. This hypothesis warrants testing in a prospective trial.

PMID- 19770747
TI  - Pressor response to fluid resuscitation in endotoxic shock: involvement of
      vasopressin.
AB  - OBJECTIVE: To investigate the effects of fluid resuscitation administration on
      vasopressin secretion and its association with pressor response in endotoxic
      shock during a period of inappropriately low vasopressin secretion. DESIGN:
      Prospective, controlled experiment. SETTING: Animal basic science laboratory.
      SUBJECTS: Male Wistar rats, weighing 250 to 300 grams. INTERVENTIONS: Rats
      received lipopolysaccharide (2 mg/kg, intravenous) and had their mean arterial
      pressure monitored during the next 4 hrs. Subsequently, the animals were assigned
      randomly to one of seven groups (n = 6 per group) that differed in the
      composition or volume of the resuscitation fluid administered: control group (no
      fluid administered); isotonic saline solution (0.9% NaCl; 4 mL/kg); hypertonic
      saline solution (7.5% NaCl; 4 mL/kg); 0.9% NaCl in 6% hydroxyethyl starch 450/0.7
      (4, 8, or 16 mL/kg); or 7.5% NaCl in 6% hydroxyethyl starch 450/0.7 (4 mL/kg).
      MEASUREMENTS AND MAIN RESULTS: Blood pressure was lower in the lipopolysaccharide
      treated group. Administration of 0.9% NaCl in 6% hydroxyethyl starch 450/0.7 did
      not change mean arterial pressure, but reduced vasopressin plasma levels at a
      dose of 16 mL/kg. Hypertonic saline solution or 7.5% NaCl in 6% hydroxyethyl
      starch 450/0.7 administration was followed by an immediate recovery of blood
      pressure and also by an increase in plasma vasopressin levels when compared to
      isotonic saline solution. The vasopressin V1 receptor antagonist (10 microg/kg,
      intravenous, 5 min before infusion) completely blunted the increase in mean
      arterial pressure induced by hypertonic saline solution or 7.5% NaCl in 6%
      hydroxyethyl starch 450/0.7 in endotoxemic rats. CONCLUSIONS: Isotonic blood
      volume expansion reduced vasopressin plasma levels. Furthermore, the subsequent
      release of vasopressin is essential for the pressor response caused by hypertonic
      fluid infusion during endotoxic shock.

PMID- 19770748
TI  - Association between timing of intensive care unit admission and outcomes for
      emergency department patients with community-acquired pneumonia.
AB  - OBJECTIVE: To compare the 28-day mortality and hospital length of stay of
      patients with community-acquired pneumonia who were transferred to an intensive
      care unit on the same day of emergency department presentation (direct-transfer
      patients) with those subsequently transferred within 3 days of presentation
      (delayed-transfer patients). DESIGN: Secondary analysis of the original data from
      two North American and two European prospective, multicenter, cohort studies of
      adult patients with community-acquired pneumonia. PATIENTS: In all, 453 non
      institutionalized patients transferred within 3 days of emergency department
      presentation to an intensive care unit were included in the analysis.
      Supplementary analysis was restricted to patients without an obvious indication
      for immediate transfer to an intensive care unit. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: The sample consisted of 138 delayed-transfer and
      315 direct-transfer patients, among whom 150 (33.1%) were considered to have an
      obvious indication for immediate intensive care unit admission. After adjusting
      for the quintile of propensity score, delayed intensive care unit transfer was
      associated with an increased odds ratio for 28-day mortality (2.07; 95%
      confidence interval, 1.12-3.85) and a decreased odds ratio for discharge from
      hospital for survivors (0.53; 95% confidence interval, 0.39-0.71). In a
      propensity-matched analysis, delayed-transfer patients had a higher 28-day
      mortality rate (23.4% vs. 11.7%; p = 0.02) and a longer median hospital length of
      stay (13 days vs. 7 days; p < .001) than direct-transfer patients. Similar
      results were found after excluding the 150 patients with an obvious indication
      for immediate intensive care unit admission. CONCLUSIONS: Our findings suggest
      that some patients without major criteria for severe community-acquired
      pneumonia, according to the recent Infectious Diseases Society of
      America/American Thoracic Society consensus guideline, may benefit from direct
      transfer to the intensive care unit. Further studies are needed to prospectively
      identify patients who may benefit from direct intensive care unit admission
      despite a lack of major severity criteria for community-acquired pneumonia based
      on the current guidelines.

PMID- 19770749
TI  - Early alterations of red blood cell rheology in critically ill patients.
AB  - OBJECTIVE: To investigate red blood cell rheology in a large intensive care unit
      population on admission, and to assess the possible influence of comorbidities on
      the rheology. DESIGN: : Prospective study. SETTING: Medico-surgical intensive
      care unit with 31 beds. SUBJECTS: All intensive care unit admissions during a 5
      month period and 20 healthy volunteers. INTERVENTIONS: Blood sampling.
      MEASUREMENTS AND MAIN RESULTS: A total of 196 intensive care patients (160
      without and 36 with sepsis) and 20 healthy volunteers were studied. Red blood
      cell rheology (deformability and aggregation) was assessed ex vivo using the
      laser-assisted optical rotational cell analyzer (LORCA; Mechatronics Instruments
      BV, AN Zwaag, Netherlands) within the first 24 hrs after intensive care unit
      admission. Red blood cell deformability was determined by the elongation index in
      relation to the shear stress (0.3 to 50 Pa) applied on the red blood cell
      membrane surface. Aggregation was assessed by the aggregation index. Septic
      patients were more likely to have anemia, coagulation abnormalities, and
      comorbidities than were nonseptic patients. Red blood cell deformability was
      significantly altered in septic compared to nonseptic patients and volunteers for
      the majority of shear stress rates studied. The aggregation index was greater in
      septic patients than in volunteers (67.9% [54.7-73.5] vs. 61.8% [58.2-68.4]; p <
      .05). Only sepsis and hematologic disease influenced the elongation index (both p
      < .01). Other comorbidities, like cancer, diabetes mellitus, cirrhosis, and
      terminal renal failure, had no effect on the elongation index. Aggregation index
      was related to the degree of organ failure (Sequential Organ Failure Assessment
      score), the red blood cell count, and fibrinogen concentrations. CONCLUSIONS:
      Early alterations of red blood cell rheology are common in intensive care unit
      patients, especially in those with sepsis. Comorbidities (other than hematologic
      diseases) do not significantly influence these abnormalities. These alterations
      could contribute to the microcirculatory alterations observed in critically ill
      patients.

PMID- 19770750
TI  - Evaluation of sublingual and gut mucosal microcirculation in sepsis: a
      quantitative analysis.
AB  - OBJECTIVE: To determine the relationship between sublingual and intestinal
      mucosal microcirculatory perfusion. DESIGN: Observational, experimental study.
      SETTING: University-affiliated large animal laboratory. SUBJECTS: Ten fasted,
      anesthetized, mechanically ventilated, male pigs randomized to a sham group (n =
      3) or to a hyperdynamic septic shock group (n = 7) in which cholangitis was
      induced by direct infusion of Escherichia coli into the common bile duct. This
      model was developed because it is not accompanied by changes in intra-abdominal
      pressure. MEASUREMENTS AND MAIN RESULTS: The sublingual and intestinal
      microcirculations were simultaneously assessed at 4-hr intervals for up to 12 hrs
      with a modified orthogonal polarization spectral device and functional
      microvessel density and erythrocyte velocity were measured quantitatively. In
      sham animals, both regions maintained a stable functional microvessel density and
      erythrocyte velocity throughout the study period. In contrast, in septic animals,
      already after 4 hrs of sepsis, functional microvessel density was markedly
      decreased (>50%) in the sublingual and gut regions; mean erythrocyte velocity
      decreased dramatically and similarly in both regions, from 1022 +/- 80 to 265 +/-
      43 mum/sec in the sublingual region and from 1068 +/- 45 to 243 +/- 115 mum/sec
      in the gut (p < 0.001, at T12). There was a significant correlation between the
      sublingual and gut microcirculations in septic animals (r = 0.92, p < 0.0001).
      CONCLUSIONS: The severity and the time course of microcirculatory changes were
      similar in the sublingual and in the gut region in this clinically relevant model
      of severe sepsis. These findings support the sublingual region as an appropriate
      region to monitor the microcirculation in sepsis.

PMID- 19770751
TI  - Presence and severity of intensive care unit-acquired paresis at time of
      awakening are associated with increased intensive care unit and hospital
      mortality.
AB  - OBJECTIVES: To assess whether the presence and severity of intensive care unit
      acquired paresis are associated with intensive care unit and in-hospital
      mortality. DESIGN: Prospective, observational study. SETTING: Two medical, one
      surgical, and one medico-surgical intensive care units in two university
      hospitals and one university-affiliated hospital. PATIENTS: A total of 115
      consecutive patients were enrolled after > 7 days of mechanical ventilation.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The Medical Research Council
      score (from 0-60) was used to evaluate upper and lower limb strength at time of
      awakening, identified as the ability to follow five commands. Intensive care unit
      acquired paresis was defined as a Medical Research Council score <48. Patients
      were followed-up until hospital discharge. The primary end point was hospital
      mortality. At awakening, median Medical Research Council score was 41
      (interquartile range, 21-52), and 75 (65%) patients had intensive care unit
      acquired paresis. Hospital non-survivors had a significantly lower Medical
      Research Council score at awakening (21 [11-43]) vs. 41 [28-53]; p = .008) and a
      significantly higher rate of intensive care unit-acquired paresis (85.1% vs.
      58.4%; p = .02) compared to survivors. After multivariate risk adjustment,
      intensive care unit-acquired paresis was independently associated with higher
      hospital and intensive care unit mortality (odds ratio for hospital mortality,
      2.02; 95% confidence interval, 1.03-8.03; p = .048). Each Medical Research
      Council point decrease was associated with a significantly higher hospital
      mortality (odds ratio, 1.03; 95% confidence interval, 1.01-1.05; p = .033).
      CONCLUSIONS: Both the presence and severity of intensive care unit-acquired
      paresis at the time of awakening are associated with increased intensive care
      unit and hospital mortality; the mechanisms underlying this association need
      further study.

PMID- 19770752
TI  - Continuous right ventricular volumetry by fast-response thermodilution during
      right ventricular ischemia: head-to-head comparison with conductance catheter
      measurements.
AB  - OBJECTIVE: To evaluate the accuracy of right ventricular ejection fraction and
      right ventricular end-diastolic volume obtained by volumetric pulmonary artery
      catheter, using the conductance catheter as reference method. DESIGN:
      Prospective, comparative study. SETTING: Research laboratory of a university
      hospital. SUBJECTS: Seven young female German landrace pigs. INTERVENTIONS:
      Ligation of the distal right coronary artery to induce temporary acute ischemia.
      MEASUREMENTS AND MAIN RESULTS: Right ventricular ejection fraction and right
      ventricular end-diastolic volume were measured simultaneously with a volumetric
      pulmonary artery catheter and the conductance catheter technique (reference
      method), in an animal model of acute right ventricular ischemia. Measurements
      were performed at baseline, during ischemia, and during reperfusion. The methods
      were compared with Bland-Altman analyses and their diagnostic accuracy to detect
      ischemia was quantified by receiver operating characteristic curve analysis. For
      right ventricular ejection fraction measurements, Bland-Altman analysis indicated
      a bias of -9.9% indicating underestimation by pulmonary artery catheter with
      limits of agreement ranging from -26% to 6.1%. The data showed a trend for more
      underestimation at higher right ventricular ejection fraction values. For right
      ventricular end-diastolic volume, a bias of 31 mL, indicating overestimation by
      pulmonary artery catheter was found. Limits of agreement ranged from -25 mL to 88
      mL. Ischemia induced a decrease in right ventricular ejection fraction and an
      increase in right ventricular end-diastolic volume, as expected, which was
      detected by conductance catheter with a significant higher diagnostic accuracy
      indicated by a receiver operating characteristic area under the curve of 0.98 (p
      < .001) and 0.92 (p < .001), respectively. Corresponding sensitivity and
      specificity were 100% and 86%, respectively, for right ventricular ejection
      fraction conductance catheter (cutoff value = <40%), and 86% and 100% for right
      ventricular end-diastolic volume conductance catheter (cutoff value = >94 mL).
      However, diagnostic accuracy for right ventricular ejection fraction pulmonary
      artery catheter and end-diastolic volume pulmonary artery catheter to detect
      ischemia was limited with area under the curve 0.76 (p = .06) and 0.57 (p = .65),
      respectively. CONCLUSIONS: Accuracy of volumetric pulmonary artery catheter in
      conditions of right ventricular ischemia is low and inadequate for diagnosis of
      right ventricular ischemia and failure.

PMID- 19770754
TI  - Immediate and long-term impact of medical emergency teams on cardiac arrest
      prevalence and mortality: a plea for periodic basic life-support training
      programs.
AB  - OBJECTIVE: To evaluate whether the introduction of a program including a medical
      emergency team responding to widened criteria together with the institution-wide
      training on basic life support of all hospital staff would decrease cardiac
      arrest prevalence and mortality in patients at risk, in the immediate and long
      term periods after the program. DESIGN: Before-after design. SETTING: Urban
      general hospital with 470 beds. PATIENTS: All patients admitted in the hospital
      between 2002 and 2006 were eligible. All patients with a medical emergency team
      activation were included. We compared cardiac arrest prevalence and mortality and
      in-hospital mortality before (2002), after (2003-2004), and long term after (2005
      2006) the program implementation. MEASUREMENTS AND MAIN RESULTS: There was a
      significant (p = .037) decrease of 27% (95% confidence interval, 2%-46%) in
      cardiac arrest occurrence, 33% decrease (p = .014) in cardiac arrest mortality
      (95% confidence interval, 8%-52%), and a nonsignificant (p = .152) decrease of
      17% (95% confidence interval, -7%-36%) in in-hospital mortality associated with
      the program implementation. No significant differences were found for any of the
      outcome variables between before and long term after periods. The main factor
      associated with in-hospital mortality was cardiac arrest. Factors affecting
      cardiac arrest were age, comorbidities, measures started before medical emergency
      team arrival and the intervention/program. The effect in the prevention of
      cardiac arrest has an adjusted relative risk, 0.646 (95% confidence interval,
      0.450-0.876) and an absolute risk reduction of adjusted relative risk, 18% (95%
      confidence interval, 6%-29%). The program prevented one cardiac arrest for every
      five medical emergency team activations. CONCLUSIONS: Widening criteria for
      hospital emergency calls together with an integrated training program may reduce
      cardiac arrest prevalence and mortality in at-risk patients. Program
      effectiveness was critically related to the staff education, awareness, and
      responsiveness to physiologic instability of the patients. Long-term
      effectiveness of the program may decrease in the absence of periodic and
      continued implementation of educational interventions.

PMID- 19770755
TI  - The renal vascular response to diabetes.
AB  - PURPOSE OF REVIEW: Diabetes mellitus is the primary cause of end-stage renal
      disease, yet the mechanisms underlying diabetic nephropathy remain ill-defined.
      The widely accepted opinion holds that events occurring early during the course
      of diabetes engender the eventual decline in renal function. This review will
      summarize recent advances (published January 2008 through June 2009) regarding
      the renal vascular and glomerular functional changes that occur during the early
      stage of diabetes. RECENT FINDINGS: Reduced C-peptide levels and increased
      cyclooxygenase-2 activity both seem to promote diabetic hyperfiltration,
      presumably via effects on afferent arteriolar tone. In addition, exaggerated
      tonic influences of K+ channels on afferent arteriolar function likely act in
      concert with impaired Ca2+ influx responses to changes in membrane potential to
      promote vasodilation. Mechanisms underlying these changes remain largely
      speculative. Diabetes may also alter autoregulation of renal blood flow and
      glomerular filtration rate, as well as provoke afferent arteriolar dilation
      secondary to alterations in proximal tubular reabsorption; however, conflicting
      evidence continues to flood the literature concerning these events. SUMMARY: New
      evidence has expanded our appreciation of the complexity of events that promote
      preglomerular vasodilation during the early stage of diabetes; however, it seems
      that the more we know, the less we understand.

PMID- 19770756
TI  - Fibroblast growth factor 23 and the future of phosphorus management.
AB  - PURPOSE OF REVIEW: To present emerging data on the role of fibroblast growth
      factor 23 (FGF23) in mineral metabolism and adverse outcomes in chronic kidney
      disease (CKD). RECENT FINDINGS: FGF23 regulates phosphorus and vitamin D
      metabolism. Its levels increase progressively beginning in early CKD, presumably
      as a physiological adaptation to maintain normal serum phosphate levels or normal
      phosphorus balance. FGF23 promotes phosphaturia and decreases production of
      calcitriol. Recent studies suggest that increased FGF23 is associated with
      mortality, left ventricular hypertrophy, endothelial dysfunction and progression
      of CKD. These results were consistently independent of serum phosphate levels.
      SUMMARY: FGF23 is emerging as a novel and exciting biomarker that may help
      identify which CKD patients might benefit most from aggressive management of
      disordered phosphorus metabolism. Future studies should determine whether
      increased FGF23 levels exert direct end-organ toxicity, such as in the heart,
      vessels and kidneys.

PMID- 19770757
TI  - Hepatocyte transplantation for correction of inborn errors of metabolism.
AB  - PURPOSE OF REVIEW: The interest in hepatocyte transplantation has been growing
      continuously in recent years and this treatment may represent an alternative
      clinical approach for patients with end stage liver disease and selected liver
      based inborn errors of metabolism. The present review summarizes the present
      status of clinical hepatocyte transplantation and identifies some recent research
      developments in this area. RECENT FINDINGS: The clinical results of hepatocyte
      transplantation to date for the treatment of inborn errors of metabolism are
      summarized in this article. Published results are encouraging and procedure
      related complications were minimal. In an attempt to overcome the worldwide
      shortage of organs, different sources of stem cells are being studied as a
      sustainable pool of cells. Other ongoing fields of research are discussed,
      including improvement of engraftment and prevention of rejection. SUMMARY:
      Considerable experience has been gained so far in the handling of hepatocytes and
      techniques for hepatocyte transplantation allowing clinical transplantation. This
      will provide a platform for the future application of new technologies,
      particularly those based on stem cells, which is hoped will increase the
      utilization of cell transplantation.

PMID- 19770758
TI  - Combining drugs and radiotherapy: from the bench to the bedside.
AB  - PURPOSE OF REVIEW: The current standard care of treatment for glioblastoma
      multiforme (GBM) is never curative and exclusively involves the use of cytoxics
      upfront (e.g., radiation and chemotherapy). Current clinical protocols involve
      the use of single-agent targeted therapies, which inhibit specific pathways.
      Given the functional redundancies present in human tumors and escape mechanisms,
      it is highly unlikely that such a monotherapy approach will be successful in the
      treatment of GBM. Future directions of therapy for GBMs will likely involve the
      use of therapeutic cocktails, including more than one target specific inhibitors
      based on tumor escape mechanism, genetic, epigenetic and molecular signatures.
      This review addresses some of the relevant issues. RECENT FINDINGS: Correlative
      clinical studies from various clinical trials and preclinical studies have
      provided the meticulous use of chemotherapeutics and radiation based on molecular
      profiling of tumors. Alkylating agents such as temozolomide lose their efficacy
      if DNA repair enzyme expression is upregulated. The alternative strategies
      include targeting the enzyme or one can use poly (ADP) ribose inhibitor to
      inhibit base excision repair pathway rather than mismatch repair pathway.
      Currently, several inhibitors in this category are in clinical trials. Next, we
      have addressed new avenues including radiosensitizers, hypoxia, metabolism,
      angiogenesis, invasive and infiltrative nature of tumors and potential molecular
      targets, which can be exploited for clinical trials. Finally, we have included
      some aspect of genome-wide association studies and correlative analysis and the
      lessons learned to design better clinical trials. SUMMARY: Advances in profiling
      the noncoding RNAs, genetic, epigenetic profiles, metabolomics, genomics and
      proteomics may uncover important resistance mechanisms in GBM. Personalized
      therapy using various therapeutic cocktails targeting these resistance mechanisms
      may prove even more effective in the future management of GBMs.

PMID- 19770753
TI  - Efficacy and safety of a phospholipid emulsion (GR270773) in Gram-negative severe
      sepsis: results of a phase II multicenter, randomized, placebo-controlled, dose
      finding clinical trial.
AB  - OBJECTIVE: To assess the survival benefit and safety profile of low-dose (850
      mg/kg) and high-dose (1350 mg/kg) phospholipid emulsion vs. placebo administered
      as a continuous 3-day infusion in patients with confirmed or suspected Gram
      negative severe sepsis. Preclinical and ex vivo studies show that lipoproteins
      bind and neutralize endotoxin, and experimental animal studies demonstrate
      protection from septic death when lipoproteins are administered. Endotoxin
      neutralization correlates with the amount of phospholipid in the lipoprotein
      particles. DESIGN: A three-arm, randomized, blinded, placebo-controlled trial.
      SETTING: Conducted at 235 centers worldwide between September 2004 and April
      2006. PATIENTS: A total of 1379 patients participated in the study, 598 patients
      received low-dose phospholipid emulsion, and 599 patients received placebo. The
      high-dose phospholipid emulsion arm was stopped, on the recommendation of the
      Independent Data Monitoring Committee, due to an increase in life-threatening
      serious adverse events at the fourth interim analysis and included 182 patients.
      MEASUREMENTS AND MAIN RESULTS: A 28-day all-cause mortality and new-onset organ
      failure. There was no significant treatment benefit for low- or high-dose
      phospholipid emulsion vs. placebo for 28-day all-cause mortality, with rates of
      25.8% (p = .329), 31.3% (p = .879), and 26.9%, respectively. The rate of new
      onset organ failure was not statistically different among groups at 26.3%, 31.3%,
      20.4% with low- and high-dose phospholipid emulsion, and placebo, respectively
      (one-sided p = .992, low vs. placebo; p = .999, high vs. placebo). Of the
      subjects treated, 45% had microbiologically confirmed Gram-negative infections.
      Maximal changes in mean hemoglobin levels were reached on day 10 (-1.04 g/dL) and
      day 5 (-1.36 g/dL) with low- and high-dose phospholipid emulsion, respectively,
      and on day 14 (-0.82 g/dL) with placebo. CONCLUSIONS: Treatment with phospholipid
      emulsion did not reduce 28-day all-cause mortality, or reduce the onset of new
      organ failure in patients with suspected or confirmed Gram-negative severe
      sepsis.

PMID- 19770759
TI  - Approval of new drugs for glioblastoma.

PMID- 19770760
TI  - Pseudoprogression and pseudoresponse in the treatment of gliomas.
AB  - PURPOSE OF REVIEW: Treatment response of brain tumours is typically evaluated
      with gadolinium-enhanced MRI using the Macdonald criteria. These criteria depend
      on changes in the area of enhancement. However, gadolinium enhancement of brain
      tumours primarily reflects impairment of the blood-brain barrier. RECENT
      FINDINGS: Combined chemo-irradiation with temozolomide may induce in 20-30% of
      cases pseudoprogression, defined as an increase of contrast-enhancement and/or
      oedema on MRI without true tumour progression. Also, full-blown radiation
      necrosis may be more frequent after combined chemo-irradiation. After treatment
      with vascular endothelial growth factor receptor signalling pathway inhibitors
      pseudoresponse is frequent: a decrease in contrast-enhancement of brain tumours
      on MRI without a decrease of tumour activity. This to some extent explains the
      high response rate without a major increase in survival after treatment with
      these agents for recurrent glioblastoma. SUMMARY: Both pseudo-phenomenona confuse
      the assessment of outcome of brain tumours in clinical practice and in clinical
      trials. To overcome these issues, alternative endpoints and response criteria are
      being developed by an international working party [response assessment in neuro
      oncology (RANO)]. It is as yet unclear to what extent alternative imaging tools
      (positron emission tomography and MRI techniques) provide more reliable
      indicators of outcome.

PMID- 19770761
TI  - Management strategies for the prevention of preterm birth. Part I: Update on
      progesterone supplementation.
AB  - PURPOSE OF REVIEW: Preterm birth (PTB) is the main cause of neonatal morbidity
      and mortality in the developed world, generating a significant public health
      burden. PTB is a complex disorder and it is unlikely that one generalized
      prevention strategy will be effective in all patients. In this review, we are
      concerned with the most recent status of two proposed modalities of PTB
      prevention: progesterone supplementation and cerclage placement. Our intention
      was to emphasize the differential applicability of these two interventions
      tailored to specific clinical presentations. RECENT FINDINGS: Progress has been
      made in developing reliable prognosticators for PTB. Ultrasound cervical length
      measurement has emerged as the single most powerful predictor. Recent randomized
      trials of progesterone supplementation have indicated the relevance of this
      objective method of screening in the selection of patients most likely to respond
      to progesterone. Similarly, in studies of cerclage, cervical length has been
      found to perform as a tool capable of reducing unnecessary intervention. SUMMARY:
      Predefined treatment strategies guiding the decision on when to proceed with
      medical or surgical PTB prophylaxis are still lacking. On the basis of the
      available evidence, we suggest a differential approach giving preferential
      consideration to either progesterone or cerclage based on obstetrical history,
      cervical surveillance, and biochemical markers of inflammation.

PMID- 19770762
TI  - Use of monoclonal antibodies in the treatment of ovarian cancer.
AB  - PURPOSE OF REVIEW: Despite the recent progress in its management, including
      surgery and chemotherapy, ovarian cancer remains the most lethal gynecological
      malignancy. One of the promising approaches that may improve patient outcome is
      the use of monoclonal antibodies (mAbs). RECENT FINDINGS: Based on the promising
      results of preclinical studies, various mAbs are currently being evaluated in
      patients with ovarian cancer. Some of them have already demonstrated favorable
      clinical outcomes in phase I/II studies and are being investigated further in
      randomized controlled studies. This review provides information on the mAbs that
      have been studied in ovarian cancer. SUMMARY: As mAbs selectively target tumor
      cells expressing tumor-associated antigens, mAb-based therapy may offer potential
      benefits such as avoiding the cytotoxic side effects on normal tissue seen with
      traditional chemotherapeutic agents. Although previous clinical studies have
      demonstrated minimal side effects of mAbs, in contrast to treatments for
      hematological malignancies and certain solid malignancies such as breast or
      colorectal cancer, mAb-based therapy has not been convincingly proven to be
      clinically effective in patients with ovarian cancer. As the preclinically
      demonstrated potential of mAb is encouraging, further investigations are needed
      to establish a more effective, specific, and less toxic treatment strategy for
      ovarian cancer.

PMID- 19770763
TI  - Current developments with peptide-based human tumor vaccines.
AB  - PURPOSE OF REVIEW: Cancer immunology became scientifically credible only some 20
      years ago with the demonstration of the existence of human tumor antigens. In
      this short time span, outcomes of cancer vaccine trials have raised hopes and
      also surfaced disappointments. This review focuses on the prospects of peptide
      based vaccines in cancer immunotherapy. RECENT FINDINGS: Accurate descriptions of
      the natural immune responses to cancer allow for a more precise targeting of such
      tumors by boosting preexisting antitumor immune responses in patients. The
      development of synthetic long-peptide vaccines avoids many of the pitfalls of
      previous vaccination trials through the presence of multiple epitopes that may
      elicit memory antitumor immune responses. Furthermore, the combination of
      standard therapy with newly developed immunomodulating agents, such as antibodies
      blocking cytotoxic T lymphocyte-associated antigen-4 or programmed death receptor
      1, and more efficient immune adjuvants has shown promising results. SUMMARY:
      Immunotherapy is becoming an effective means of targeting human cancers, and the
      application of such approaches in combination with current standard schemes of
      treatment can lead to a significant benefit in survival and quality of life for
      cancer patients.

PMID- 19770764
TI  - Acute myeloid leukemia with mutated NPM1: diagnosis, prognosis and therapeutic
      perspectives.
AB  - PURPOSE OF REVIEW: Nucleophosmin (NPM1) gene mutations, which cause aberrant
      cytoplasmic expression of nucleophosmin (NPMc+), are the most frequent genetic
      alteration in acute myeloid leukemia (AML), being found in about 30% cases. The
      present review summarizes recent advances in the biology, diagnosis, prognosis
      and therapy of NPM1-mutated AML. RECENT FINDINGS: Diagnostic criteria of NPM1
      mutated AML are discussed in the light of its recent inclusion in the 2008 WHO
      classification of myeloid neoplasms. We also outline the most recent findings on
      prognosis and monitoring of minimal residual disease in NPM1-mutated AML and
      their implications for therapeutic decisions. Moreover, new insights are
      presented into the molecular mechanisms underlying perturbed nucleophosmin
      traffic in NPM1-mutated AML, which provides the rationale for the development of
      targeted therapies. SUMMARY: AML with mutated NPM1 is a leukemia entity with
      distinct molecular, pathological, and prognostic features.

PMID- 19770765
TI  - Issues in obesity monitoring, screening and subsequent treatment.
AB  - PURPOSE OF REVIEW: Despite intense policy, media and research interest, childhood
      obesity rates continue to rise in most countries. Screening may seem a logical
      response to a situation in which obesity does not usually resolve spontaneously,
      yet most obese children do not present for treatment. This article explores
      recent evidence for and against monitoring and screening of children's BMI.
      RECENT FINDINGS: Whether conducted in primary care or school settings, population
      screening of children's BMI can be feasible, acceptable and not intrinsically
      harmful. However, it incurs a substantial cost, and randomized controlled trials
      do not suggest that it improves BMI outcomes. Population trends in BMI are more
      complex than a simple rise in obesity; birth cohorts with higher rates of
      childhood overweight are not inevitably more overweight as young adults. The
      consequences of a concomitant increase in thinness are uncertain. SUMMARY:
      Systematic monitoring of BMI is essential, but need not be continuous, and could
      involve representative samples rather than all individuals in a population. In
      contrast, BMI screening cannot be recommended until more effective management
      becomes available for overweight and mildly obese children. Research into
      prevention and intervention should, therefore, be prioritized over population
      screening at this point in time.

PMID- 19770766
TI  - Neonatal innate immunity in allergy development.
AB  - PURPOSE OF REVIEW: The neonate is born with a distinct immune system that is
      biased against the production of T-helper cell 1 (Th1) cytokines. Birth imposes a
      great challenge on the neonatal immune system, which is confronted with an
      outside world rich in foreign antigens. Exposure to these antigens shapes the
      developing neonatal immune system. Inducing Th-1 or Th-2 polarized responses that
      may extend beyond the neonatal age and counteract or promote allergic
      sensitization. This review describes how engagement of the innate immune system
      might contribute to the development of allergy in children. RECENT FINDINGS: The
      exact role of innate immune stimulation in the development of allergies is a
      controversial area. Epidemiological literature suggests that microbial exposure
      in early childhood protects against the development of allergies, whereas a large
      amount of experimental data demonstrates that innate immune stimulation enhances
      Th2 responses upon primary and secondary antigen exposure. SUMMARY: Dose, site
      and timing of allergen exposure are likely to modulate the innate immune
      response, polarizing the maturing neonatal immune system towards Th1 or Th2-type
      responses, thereby protecting from or predisposing to asthma and allergies.
      Modulation of neonatal innate immune responses may be a novel approach to prevent
      asthma and allergies.

PMID- 19770767
TI  - Why physicians must understand evolution.

PMID- 19770768
TI  - The importance of the development of the intestinal microbiota in infancy.
AB  - PURPOSE OF REVIEW: The development of the intestinal microbiota occurs primarily
      during infancy, and a distortion could potentially contribute to a wide range of
      diseases. This review summarizes the current understanding of the intestinal
      microbiota in infants. The potential consequences of different colonization
      patterns on child health and possible preventive interventions are discussed.
      RECENT FINDINGS: Recent studies and the use of culture-independent techniques
      have shown that Bifidobacterium is only a minor component of the infant gut
      microbiota. These techniques have also introduced the concept of a core
      microbiome in which metabolic function is more important than the presence of a
      particular bacterial species. A less diverse gut microbiota with high counts of
      Bacteroides, Clostridium, Enterobacteriaceae and Staphylococcus early in life has
      been associated with an increased risk for atopic disease. Changes in infant gut
      colonization were also found in relation to childhood obesity. Probiotics have no
      proven preventive effect on the development of asthma and an unconfirmed effect
      on atopic dermatitis. A prebiotic trial could show a preventive effect on the
      development of both atopic diseases. SUMMARY: Molecular techniques have improved
      our understanding of the infant gut ecosystem. The available probiotics for
      prevention of atopic disease are disappointing, and the results with prebiotics
      need further confirmation. New studies on the relation between gut microbiota and
      disease should consider asthma and atopic dermatitis separately. Future trials
      should focus on high-risk groups, determine their long-term effect and also
      investigate the effect on Bacteroides and Clostridium.

PMID- 19770769
TI  - History and philosophy.

PMID- 19770770
TI  - Nothing about us without us!

PMID- 19770771
TI  - Mania and attention-deficit/hyperactivity disorder: common symptomatology, common
      pathophysiology and common treatment?
AB  - PURPOSE OF REVIEW: Attention-deficit/hyperactivity disorder (ADHD) and mania show
      broad symptom overlap, and high comorbidity exists between ADHD and bipolar
      disorder. This raises the question concerning common neurobiological
      pathomechanisms and concerning common treatments. RECENT FINDINGS: On genetic,
      biochemical, electrophysiological, brain morphological and neuropsychological
      levels, the commonalities of ADHD and mania and the commonalities between ADHD
      and bipolar disorder (independent of manic state) are outlined. An intriguing
      finding is that both ADHD and mania are characterized by an unstable wakefulness
      regulation assessed by EEG measures of vigilance, by ratings of sleepiness and by
      deficits in sustained attention tasks. In both mania and ADHD, this unstable
      wakefulness regulation is supposed to be a central pathogenetic factor leading to
      attention deficits and inducing the hyperactive, impulsive and sensation-seeking
      behavior as an autoregulatory attempt to stabilize wakefulness by increasing
      external stimulation. Evidence is accumulating to suggest that psychostimulants
      do not have a high risk of triggering or aggravating mania, but might even be a
      treatment option in acute mania. SUMMARY: ADHD and mania share many symptoms and
      several pathogenetic aspects. The common belief that stimulants are
      contraindicated in mania has been challenged, and controlled trials to study the
      possible antimanic effects of vigilance-stabilizing drugs such as stimulants are
      justified and necessary.

PMID- 19770772
TI  - On influenza and school closings: time for prospective studies.

PMID- 19770773
TI  - Association between school closure and subsequent absenteeism during a seasonal
      influenza epidemic.
AB  - BACKGROUND: Mathematical models suggest that social distancing measures, such as
      school closures, may mitigate community transmission during an influenza
      pandemic. Because closures are disruptive to schools and families, they are
      rarely employed during seasonal influenza outbreaks. A rare circumstance enabled
      us to examine the association between school closure and absenteeism during a
      seasonal influenza outbreak when half of King County, Washington public schools
      closed for a winter recess 19-23 February 2007, while half remained open for all
      or part of the week. METHODS: Using absenteeism as a proxy for influenza
      activity, we tested the hypothesis that schools on break would experience lower
      rates of post-break absenteeism than schools remaining open. We conducted daily
      retrospective and prospective surveillance from 5 February-9 March 2007 in
      schools on break (n = 256) and in session (n = 205). We use generalized
      estimating equations with Poisson distribution to evaluate whether mean
      absenteeism after the break differed between schools on break and those in
      session, adjusting for baseline absenteeism and repeated measurements by schools
      over time. RESULTS: Results indicate no difference in post-break absenteeism in
      schools on break compared with schools that remained in session (relative risk =
      1.07 [95% confidence interval = 0.96-1.20]). This result held in elementary
      schools (1.00 [0.91-1.10]), where absenteeism patterns are thought to be most
      representative of community influenza activity. CONCLUSION: We did not find that
      school closure during a seasonal influenza outbreak reduced subsequent
      absenteeism. However, limitations in this "natural experiment" hampered our
      ability to detect a benefit if one truly was present.

PMID- 19770774
TI  - Clinical and technical determinants of long-term performance of coronary sinus
      leads.
AB  - OBJECTIVES: Little is known about coronary sinus lead performance in patients
      with cardiac resynchronization therapy devices. We evaluated the impact of
      clinical and technical parameters on coronary sinus lead performance over long
      term follow-up. METHODS: From February 1999 to July 2004, 235 patients (181 men;
      mean age, 68 +/- 9 years; mean left ventricular ejection fraction, 26.5 +/- 6.5%;
      idiopathic dilated cardiomyopathy, 49%; ischemic, 48%; and other cause, 3%)
      underwent cardiac resynchronization therapy (pacemaker or defibrillator)
      implantation. RESULTS: On implantation, the only statistically significant
      difference was observed in mean pacing impedance, which was lower for unipolar
      leads than for bipolar leads (763 +/- 250 vs. 847 +/- 270 Omega, P = 0.02), and
      lower in patients with ischemic cardiomyopathy than in those with idiopathic
      cardiomyopathy (758 +/- 204 vs. 837 +/- 291 Omega, P = 0.03). After a mean follow
      up of 41.7 +/- 14.7 months, a significant decrease was observed in mean pacing
      impedance (from 811 +/- 261 to 717 +/- 284 Omega, P = 0.0026) and mean R-wave
      amplitude (from 13.2 +/- 6.7 to 10.5 +/- 5.5 mV, P = 0.002), whereas the mean
      pacing energy threshold increased from 3.6 +/- 10.4 to 9.5 +/- 28 microJ (P =
      0.004). On analysis of variance, unipolar lead (P = 0.016) and posterior coronary
      sinus position (P = 0.049) were related to a greater energy threshold increase.
      On multivariate analysis (Cox regression), only posterior coronary sinus lead
      position (P = 0.013) proved to be an independent predictor of long-term
      significant increase in the stimulation energy threshold. CONCLUSION: Over the
      long-term follow-up of coronary sinus leads, pacing impedance and R-wave
      amplitude decreased, whereas the energy threshold increased; unipolar leads and
      posterior lead location in the coronary sinus were related to a greater energy
      threshold increase.

PMID- 19770775
TI  - Postinfarction septal dissection and rupture evolved as an inferobasal
      pseudoaneurysm: a specific anatomical pattern.
AB  - In rare cases of posterior myocardial infarction, septal rupture is the
      consequence of a dissecting interventricular hematoma that evolves as a fibrotic
      septal chamber with two separate communications, towards left and right
      ventricle. This unusual anatomical pattern is generally unsuspected and described
      as a normal interventricular defect associated with a basal left ventricular
      aneurysm or pseudoaneurysm. We present a case where echocardiography and
      ventricular angiography did not detect this situation. As surgical implications
      are important, this peculiar anatomical pattern should be suspected especially in
      patients with asymptomatic postinfarction posterior septal rupture or in those
      with minimal clinical impairment.

PMID- 19770776
TI  - Biomarkers of inflammation and endothelial dysfunction and risk of hypertension
      among Inner Mongolians in China.
AB  - OBJECTIVE: We examined the association between plasma concentrations of high
      sensitivity C-reactive protein, soluble intercellular adhesion molecule 1,
      soluble E-selectin, angiotensin II, renin activity and the risk of hypertension
      among 2589 study participants aged 20 years and older from Inner Mongolia, China.
      METHODS: Three blood pressure measurements were obtained using a standard mercury
      sphygmomanometer and hypertension was defined as blood pressure of at least
      140/90 mmHg or use of antihypertensive medications. Overnight fasting blood
      samples were obtained to measure the biomarkers of endothelial dysfunction and
      inflammation. RESULTS: The average levels of high-sensitivity C-reactive protein
      (7.5 vs. 5.4 mg/l), soluble intercellular adhesion molecule 1 (339.4 vs. 322.6
      ng/ml), soluble E-selectin (19.1 vs. 18.2 ng/ml), and angiotensin II (52.0 vs.
      47.0 pg/ml) were significantly higher, whereas renin activity (1.3 vs. 1.5
      mg/ml.h) was lower in hypertensive compared to normotensive participants (all P
      value <0.001). Compared to the lowest quartile, the multivariable-adjusted odds
      ratios (95% confidence interval) of hypertension for the highest quartile were
      1.41 (1.06, 1.86) for high-sensitivity C-reactive protein, 1.93 (1.48, 2.53) for
      angiotensin II, and 0.70 (0.54, 0.91) for renin activity. CONCLUSION: Our study
      indicated that elevated plasma levels of high-sensitivity C-reactive protein and
      angiotensin II were positively and renin activity inversely associated with the
      risk of hypertension. These data suggest that inflammation and endothelial
      dysfunction may play a role in the cause of hypertension.

PMID- 19770777
TI  - Genotype-phenotype analysis of angiotensinogen polymorphisms and essential
      hypertension: the importance of haplotypes.
AB  - OBJECTIVES: To better understand the relationship between angiotensinogen (AGT)
      genetic variation and essential hypertension, AGT genotypes and haplotypes were
      tested for association with hypertensive endophenotypes and essential
      hypertension. METHODS: Two hundred and fifty-six Hypertensive Pathotype
      (HyperPATH)/Specialized Center of Research (SCOR) cases and 126 controls were
      genotyped for 24 single-nucleotide polymorphisms (SNPs) in the AGT gene. SNPs and
      AGT haplotypes were tested for association with plasma AGT, renal plasma flow
      (RPF), and essential hypertension. RESULTS: New associations between essential
      hypertension, plasma AGT, and RPF are reported for alleles -1178G, 6066A, 6152A,
      6233C, and 12822C. The maximum odds ratio for association of hypertension and AGT
      genetic variation was 2.3 [95% confidence interval (CI) 1.5-3.8; P < 0.0003] for
      allele 6233C. Previous associations for -1074T, -532T, -217A, -6A, and 4072C are
      confirmed (P < 0.05). Sodium depletion enhances associations between AGT SNPs and
      plasma AGT. Most individually associated SNPs, including -6A and 4072C, are found
      on a common complete AGT haplotype, H4 (frequency = 0.09). Individuals with
      haplotype H4 have significantly higher plasma AGT and reduced RPF (P < 0.003 and
      P < 0.0002, respectively). Other common haplotypes are not associated with
      increased plasma AGT levels in this data set despite the presence of the -6A and
      4072C alleles, suggesting that AGT haplotype H4 is more predictive of elevated
      plasma AGT than is -6A or 4072C. CONCLUSION: This study demonstrates the
      importance of analyzing haplotypes in addition to single genotypes in association
      studies. By demonstrating the dependence of AGT associations on sodium depletion
      status, it helps to explain previous conflicting association results.

PMID- 19770778
TI  - The impact of an electronic monitoring and reminder device on patient compliance
      with antihypertensive therapy: a randomized controlled trial.
AB  - BACKGROUND: High blood pressure (BP) significantly increases overall
      cardiovascular risk, the incidence of ischemic heart disease and stroke. One of
      the most important causes of insufficient BP control is low treatment compliance.
      Reminders and electronic compliance monitoring have been shown to be effective in
      improving patient compliance to some extent, but the combined effect has not been
      documented. OBJECTIVE: To assess the impact of an electronic reminder and
      monitoring device on patient compliance and BP control. METHODS: All patients
      received medical treatment with telmisartan once daily and were randomized to
      either electronic compliance monitoring with a reminder and monitoring device or
      standard therapy for 6 months. Both groups were crossed over after 6 months.
      Intervention effectiveness was assessed using self-reported compliance and BP.
      RESULTS: Data from 398 patients were analysed. In the first half of the study,
      patients using the device reported 91% compliance versus 85% in the control
      group. This difference diminished after crossover (88 versus 86%). BP was not
      affected. Electronic monitoring data on compliance revealed taking, dosing and
      timing compliance between 45 and 52% in study group 1, and between 32 and 38% in
      study group 2. CONCLUSION: The Helping Hand reminder device was most suitable if
      used for newly diagnosed hypertensive patients, when it improved compliance by
      6%. With the present medical treatment, the device does not have any influence on
      BP control, but with less forgiving medications, the device might make a
      significant difference. The use of the device can be an easy and effective way to
      improve compliance in selected patients.

PMID- 19770779
TI  - Role of nursing unit factors on performance of phlebotomy and subsequent blood
      culture contamination rates.
AB  - Institutions have a duty to respond when blood culture contamination rates exceed
      the accepted national average of 3% to 4% and to identify risk factors so that
      interventions can be instituted. This study outlines work environment risk
      factors that can influence blood culture contamination rates. Development of
      interventions aimed at changing behaviors to improve these conditions may result
      in improvement in patient care, reduction in healthcare costs, and reduction in
      bacterial resistance.

PMID- 19770780
TI  - Cardiovascular hemodynamics during stress in premenopausal versus postmenopausal
      women.
AB  - OBJECTIVE: After menopause, women are at an increased risk of cardiovascular
      disease. The present study assessed cardiovascular hemodynamics in premenopausal
      versus postmenopausal women, with a focus on systemic vascular resistance (SVR)
      at rest and during stress. Sympathetic nervous system activity and cardiovascular
      adrenergic receptor (AR) function were also examined. METHODS: A total of 90
      women (45 premenopausal and 45 postmenopausal) completed a laboratory protocol
      composed of a resting baseline and four mental stress tasks. Measurements
      included blood pressure, cardiac output, SVR, and plasma catecholamine level. In
      addition, alpha- and beta-AR responsiveness to the infusion of selective
      pharmacological agonists was assessed. RESULTS: Compared with premenopausal
      women, postmenopausal women were characterized by similar blood pressure but
      lower cardiac output and higher SVR, both at rest and during stress (Ps < 0.05).
      Postmenopausal women also had higher baseline plasma norepinephrine levels (P =
      0.007) and reduced beta-AR responsiveness (P = 0.02), although differences in
      beta-AR responsiveness may have been confounded by aging effects. CONCLUSIONS:
      After menopause, women exhibit altered sympathetic nervous system activity and a
      sustained increase in hemodynamic load that may contribute to pathological
      structural and functional changes in the heart and blood vessels.

PMID- 19770781
TI  - Hormone therapy and intraocular pressure in nonglaucomatous eyes.
AB  - OBJECTIVE: The influence of sex hormones on intraocular pressure (IOP) has been
      the focus of recent debate. Previous studies investigating the effects of hormone
      therapy (HT) on IOP in postmenopausal women have produced conflicting results but
      have been limited by small numbers of participants. The aim of our study was to
      compare IOP in women without glaucoma taking HT with those not taking HT.
      METHODS: A prospective cross-sectional study of postmenopausal women visiting a
      single ophthalmic medical practitioner was conducted. All women with a history of
      intraocular disease, a family history of glaucoma, or refractive error exceeding
      +/-5 diopters were excluded. Applanation tonometry was used to measure IOP, and
      participants were then asked if they were current HT users. RESULTS: A total of
      263 participants were recruited, of whom 91 reported current use of HT; 172 had
      never used HT. Within the HT group, 33 were taking an estrogen-therapy and 58
      were taking a estrogen-progesterone therapy. Mean IOP in the HT group was
      significantly lower than that in the non-HT group; the mean difference was 1.41
      mm Hg (P < 0.001). This difference remained statistically significant after
      statistical correction for age, use of systemic beta-blockers, and time of IOP
      measurement. There was no significant difference in mean IOP between women taking
      combined versus those taking estrogen-only preparations. CONCLUSIONS: Our study
      showed that IOP was significantly lower in women taking HT than in those who had
      never taken HT, even after removing other possible influences on IOP. The IOP
      lowering effect of HT deserves further investigation to explore whether it may
      represent a possible new therapeutic modality for glaucoma.

PMID- 19770782
TI  - Leflunomide: is a new oral agent in treatment of acute pancreatitis?
AB  - OBJECTIVES: Nuclear factor-kappaB (NF-kappaB) is a potent mediator in several
      steps of acute pancreatitis. Leflunomide is a novel immunomodulating drug that is
      also a potent inhibitor of NF-kappaB activation. The aim of this study was to
      investigate the effects of leflunomide pretreatment in severe necrotizing
      pancreatitis in rats. METHODS: Fifty rats were randomly divided into 5 groups.
      Severe necrotizing pancreatitis was induced by retrograde injection of 3% sodium
      taurocholate into the common biliopancreatic duct. Leflunomide (10 mg/kg) was
      given intragastrically for 2 doses before the experiment. Serum amylase activity,
      pancreatic histopathologic condition, malondialdehyde level, myeloperoxidase
      enzyme activity, nitric oxide level, and pulmonary changes were assessed.
      RESULTS: Leflunomide pretreatment significantly ameliorated pancreatic
      hemorrhage, edema, and neutrophil infiltration and decreased histopathological
      score compared with the untreated severe necrotizing pancreatitis group
      (pathological score [mean +/- SEM]: 6.70 +/- 1.19 vs 12.36 +/- 1.08 in the
      leflunomide treated and untreated groups, respectively, P < 0.01). Pulmonary
      changes was decreased in the leflunomide treated group (3.90 +/- 0.45 vs 4.75 +/-
      0.25, respectively). Change in pulmonary alveolar distention was significant.
      Although serum amylase levels also decreased, the difference was not significant
      (5922 +/- 3290 vs 15547 +/- 5090 U/mL). CONCLUSIONS: Leflunomide is a beneficial
      agent in the severe form of acute pancreatitis in rats and should be considered
      as a potential agent for treatment of acute pancreatitis.

PMID- 19770783
TI  - Rat pancreatic beta cells and cytomegalovirus infection.
AB  - OBJECTIVES: Cytomegalovirus (CMV) infection has been suggested to accelerate beta
      cell destruction and thereby to contribute to new-onset diabetes and failure of
      islet allografts in both humans and rodents. Surprisingly, direct CMV infection
      of beta cells has received only minor attention. Therefore, we investigated the
      susceptibility of rat beta cells for rat CMV (RCMV) infection and the direct
      effects on the regulation of immune cell-activating ligands. METHODS: Primary rat
      beta cells, the rat beta-cell line Rin-m5F, and fibroblasts were RCMV-infected in
      vitro. The viral gene and protein expression levels were determined as a measure
      for RCMV susceptibility. Gene expression levels of intracellular adhesion
      molecule 1, lymphocyte function associated antigen 3, rat major
      histocompatibility complex region A, rat major histocompatibility complex region
      E, toll like receptor 2, and clustered domain 14 were determined as a measure for
      cellular immunogenicity. RESULTS: We demonstrate that beta cells are susceptible
      for RCMV infection but allow only low levels of viral gene expression. In
      contrast, infected fibroblasts demonstrated productive viral infection and
      formation of viral progeny. After RCMV infection, beta-cell immunogenicity was
      markedly increased, as demonstrated by the increased cellular expression of
      immune cell-activating ligands. CONCLUSIONS: Direct beta-cell infection by RCMV
      and subsequent low-grade viral gene expression may lead to increased
      immunogenicity of native or transplanted beta cells in vivo. An infection-induced
      enhanced beta-cell recognizability may have important consequences for beta-cell
      survival and the development of diabetes or rejection of islet grafts.

PMID- 19770785
TI  - Diagnosis of ventilator-associated pneumonia in children in resource-limited
      setting: a comparative study of bronchoscopic and nonbronchoscopic methods.
AB  - OBJECTIVES: To compare the available methods for the diagnosis of ventilator
      associated pneumonia in intubated pediatric patients and to suggest less costly
      diagnostic method for developing countries. DESIGN: Prospective study. SETTING:
      Pediatric intensive care unit of a tertiary care, multidisciplinary teaching
      hospital located in northern India. PATIENTS: All consecutive patients on
      mechanical ventilation for >48 hrs were evaluated clinically for ventilator
      associated pneumonia. INTERVENTIONS: Four diagnostic procedures (tracheal
      aspiration, blind bronchial sampling, blind bronchoalveolar lavage, and
      bronchoscopic bronchoalveolar lavage) were performed in the same sequence within
      12 hrs of clinical suspicion of ventilator-associated pneumonia. The bacterial
      density > or =104 colony-forming units/mL in a bronchoscopic bronchoalveolar
      lavage sample was taken as reference standard. MEASUREMENTS AND MAIN RESULTS:
      Thirty patients with 40 episodes of ventilator-associated pneumonia were included
      in the study. Tracheal aspirate at the cutoff of > or =105 colony-forming
      units/mL was found to have sensitivity, specificity, positive predictive value,
      negative predictive value, and accuracy of 84%, 77%, 87.5%, 73%, and 80%,
      respectively. For blind bronchial sampling at > or =104 colony-forming units/mL
      cutoff, the sensitivity, specificity, positive predictive value, negative
      predictive value, and accuracy were 88%, 82%, 88%, 83%, and 87%, respectively;
      the most reliable results were obtained with blind bronchoalveolar lavage at the
      cutoff of > or =103 cfu/mL (sensitivity 96%, specificity 80%, positive predictive
      value 88%, negative predictive value 92%, and accuracy 90%). The area under the
      receiver operating characteristic curve of tracheal aspiration, blind bronchial
      sampling, and blind bronchoalveolar lavage was 0.87 +/- 0.06, 0.89 +/- 0.06, and
      0.89 +/- 0.05, respectively. The cost of balloon-tip pressure catheter used for
      blind bronchoalveolar lavage was INR 1600.00 (US$40) whereas that for blind
      bronchial sampling was only INR 35.00 (<1 US$). CONCLUSIONS: Blind
      bronchoalveolar lavage was the most reliable method followed closely by blind
      bronchial sampling for the diagnosis of ventilator-associated pneumonia.
      Considering the difference of the cost in the two procedures, blind bronchial
      sampling may be the preferred method in the pediatric intensive care unit of a
      developing country.

PMID- 19770784
TI  - Pdx-1 regulation of the INGAP promoter involves sequestration of NeuroD into a
      non-DNA-binding complex.
AB  - OBJECTIVE: Islet neogenesis-associated protein (INGAP) can enhance beta-cell mass
      to offset progression of diabetes. Identifying how transcription factors regulate
      INGAP gene expression could reveal key checkpoints governing islet neogenesis.
      METHODS: Protein complex interactions at the INGAP promoter were detected using a
      beta-galactosidase reporter, these protein-DNA complexes being validated in
      competitive electrophoresis mobility shift assays. The relevance of the revealed
      promoter interactions was confirmed in small interfering RNA (siRNA) gene
      knockdown studies. RESULTS: Pdx-1 negatively regulates stimulation of the INGAP
      promoter by Pan-1/NeuroD. Independently, Pdx-1, Pan-1, and NeuroD bind to the
      INGAP promoter as revealed by electrophoresis mobility shift assay studies. In
      combination, Pdx-1 selectively displaces NeuroD from a DNA-binding complex with
      Pan-1 to form a non-DNA-binding unit. The importance of this interaction is shown
      in HIT cells that have a forced reduction of Pdx-1 expression. In siRNA/Pdx-1
      depleted HIT cells, the interaction of Pan-1/NeuroD with the INGAP promoter is
      increased 6-fold. Furthermore, endogenous INGAP expression is detected in Pdx-1
      depleted cells. CONCLUSIONS: These data reveal a dynamic interaction between Pdx
      1, NeuroD, and Pan-1 for the regulation of INGAP promoter activity. Modulating
      molecular regulators of DNA expression may be a consideration in diabetic
      therapies that translate exogenous stimuli into new endogenous beta-cell mass.

PMID- 19770786
TI  - Extended-interval gentamicin: population pharmacokinetics in pediatric critical
      illness.
AB  - OBJECTIVES: Once-daily gentamicin therapy is becoming increasingly common in
      pediatric practice; however, little is known about pharmacokinetics in critical
      illness. Gentamicin exhibits concentration dependant killing; thus, peak serum
      concentrations at least eight times higher than minimum inhibition concentration
      of the target organism have been recommended. We wanted to derive pharmacokinetic
      parameters for gentamicin in critical illness and to evaluate whether a dose of 8
      mg/kg provides an adequate peak serum concentration (>16 mg/L). PATIENTS AND
      INTERVENTIONS: Population-based pharmacokinetic analyses were undertaken using
      therapeutic drug monitoring data collected prospectively in an intensive care
      unit over 6 months (n = 50 children). Monte Carlo simulations were used to
      estimate the probability of achieving 1) peak concentrations >16 mg/L; and 2)
      trough concentrations <2 mg/L at 24 and 36 hrs. MEASUREMENTS AND MAIN RESULTS:
      The optimal pharmacokinetic model was of two-compartment disposition with zero
      order input and additive residual error. Weight was associated nonlinearly with
      clearance and linearly with volume, and age was a significant covariate for
      clearance. An 8-mg/kg dose provided near 100% probability of achieving adequate
      peak concentrations at all ages. However this probability decreased rapidly at
      doses <7 mg/kg with neonates being the most susceptible. Approximately 50% of
      nonpremature neonates within the first week of life, 25% of infants, and 10% of
      children are likely to need a dose interval >24 hrs. CONCLUSIONS: A gentamicin
      dose of 8 mg/kg is highly likely to achieve peak concentrations >16 mg/L in
      critically ill children. A considerable proportion will require dose intervals
      >24 hrs; thus, therapeutic drug monitoring is essential.

PMID- 19770787
TI  - Building trust through communication in the intensive care unit: HICCC.
AB  - OBJECTIVE: The goal of this study was to explore the role of communication in
      building trust between intensivists and parents in the pediatric intensive care
      unit. METHODS: Semistructured qualitative interviews were administered to English
      speaking parents of children who were admitted to the pediatric intensive care
      unit for at least 48 hrs. Parents were asked about the factors impacting trust
      and communication in the pediatric intensive care unit. Qualitative data were
      managed with NVIVO software (QSR International, Southport, UK) and analyzed for
      themes. RESULTS: Participants were 122 parents (41% black, 40% white). Most
      parents articulated that communication is integral to building trust.
      Specifically, parents described that they wanted healthcare workers to
      communicate in ways that were Honest, Inclusive, Compassionate, Clear and
      Comprehensive, and Coordinated, which can be summarized using the acronym, HICCC.
      In addition, nonwhite parents were more likely than white parents to report
      instances when they felt doctors did not listen to them (p = 0.0083). Parents
      from minority groups reported instances of self-experienced or observed
      discrimination in healthcare with greater frequency than white parents. When
      asked to identify their pediatric intensive care unit doctor, 46% of parents were
      either unable to do so or named doctors from other hospital departments.
      CONCLUSIONS: Communication is vital to building trust in the pediatric intensive
      care unit. Developed from parents' own observations and perspectives, HICCC is an
      accessible framework that can help doctors to remember what parents value in
      communication in the acute care setting. In addition, pediatric intensivists
      would benefit from targeted cultural competency training to reduce physician
      bias.

PMID- 19770788
TI  - Stress ulcer, gastritis, and gastrointestinal bleeding prophylaxis in critically
      ill pediatric patients: a systematic review.
AB  - OBJECTIVE: To identify and evaluate the quality of evidence supporting
      prophylactic use of treatments for stress ulcers and upper gastrointestinal
      bleeding. Stress ulcers, erosions of the stomach and duodenum, and upper
      gastrointestinal bleeding are well-known complications of critical illness in
      children admitted to the pediatric intensive care unit. DATA SOURCES: Studies
      were identified from the Cochrane Central Register of Controlled Trials, PUBMED;
      LILACS; Scirus. We also scanned bibliographies of relevant studies. STUDY
      SELECTION: This systematic review of randomized controlled trials assessed the
      effects of drugs for stress-related ulcers, gastritis, and upper gastrointestinal
      bleeding in critically ill children admitted to the pediatric intensive care
      unit. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted the
      relevant data. Most randomized controlled trials were judged as having unclear
      risk of bias. When pooling two randomized controlled trials, treatment was
      significantly more effective in preventing upper gastrointestinal bleeding
      (macroscopic or important bleeding) compared with no treatment (two studies = 300
      participants; relative risk, 0.41; 95% confidence interval, 0.19-0.91; I = 12%).
      Meta-analysis of two studies found no significant difference in death rates among
      groups (two randomized controlled trials = 132 participants; relative risk, 1.39;
      95% confidence interval, 0.70-2.79; I = 4%). The rate of pneumonia was not
      significantly different when comparing treatment and no treatment in one study.
      When comparing ranitidine with no treatment, significant differences were found
      in the proportion of mechanically ventilated children with normal gastric mucosal
      endoscopic findings by histologic specimens (one randomized controlled trial = 48
      participants; relative risk, 3.53; 95% confidence interval, 1.34-9.29). No
      significant differences were found when comparing different drugs (omeprazole,
      ranitidine, sucralfate, famotidine, amalgate), doses, or regimens for main
      outcomes (deaths, endoscopic findings of erosion or ulcers, upper
      gastrointestinal bleeding, or pneumonia). CONCLUSIONS: Although pooled data of
      two studies suggested that critically ill pediatric patients may benefit from
      receiving prophylactic treatment to prevent upper gastrointestinal bleeding, we
      found that high-quality evidence to guide clinical practice is still limited.

PMID- 19770789
TI  - Developmental neurotoxicity of sedatives and anesthetics: a concern for neonatal
      and pediatric critical care medicine?
AB  - OBJECTIVE: To evaluate the currently available evidence for the deleterious
      effects of sedatives and anesthetics on developing brain structure and
      neurocognitive function. DESIGN: A computerized, bibliographic search of the
      literature regarding neurodegenerative effects of sedatives and anesthetics in
      the developing brain. MEASUREMENTS AND MAIN RESULTS: A growing number of animal
      studies demonstrate widespread structural damage of the developing brain and long
      lasting neurocognitive abnormalities after exposure to sedatives commonly used in
      neonatal and pediatric critical care medicine. These studies reveal a dose and
      exposure time dependence of neuronal cell death, characterize its molecular
      pathways, and suggest a potential early window of susceptibility in humans.
      Several clinical studies document neurologic abnormalities in neonatal intensive
      care unit graduates, usually attributed to comorbidities. Emerging human
      epidemiologic data, however, do not exclude prolonged or repetitive exposure to
      sedatives and anesthetics in early childhood as contributing factors to some of
      these abnormalities. CONCLUSIONS: Neuronal cell death after neonatal exposure to
      sedatives and anesthetics has been clearly demonstrated in developing animal
      models. Although the relevance for human medicine remains speculative, the
      phenomenon's serious implications for public health necessitate further
      preclinical and clinical studies. Intensivists using sedatives and anesthetics in
      neonates and infants need to stay informed about this rapidly emerging field of
      research.

PMID- 19770790
TI  - Unexpected cloud-like lesion on gallium-67 scintigraphy: detection of
      subcutaneous abscess underneath the skin with normal appearance in a comatose
      patient in an intensive care setting.

PMID- 19770791
TI  - Bartter's syndrome in pregnancy: review of potassium homeostasis in gestation.
AB  - A 26-year-old G3P2 Hispanic female presented with acute urinary retention and
      profound hypokalemia (serum potassium 1.6 mEq/L) during her 13th week of
      pregnancy. Placement of an indwelling bladder catheter resulted in immediate
      urine output of 1700 mL. Potassium was administered aggressively and urinary
      retention resolved. She reported the use of herbal products containing licorice
      and corn silk tea (zea maize extract). She was taking no medication other than
      prenatal vitamins and had no known prior medical problems. Despite discontinuance
      of the herbal supplement and tea and aggressive oral potassium replacement,
      severe asymptomatic hypokalemia persisted. Twenty-four-hour urine studies and
      blood chemistry determinations, subsequently, were consistent with Bartter's
      syndrome. At the time of hospital discharge, she was receiving 480 mEq of oral
      potassium daily. Potassium-sparing diuretics were not prescribed, because
      successful pregnancy outcomes have been reported in patients with Bartter's
      syndrome and Gitelman syndrome without normalization of potassium levels.
      Hypokalemia (2.5-3.0 mEq/L) persisted throughout an otherwise uncomplicated
      pregnancy with delivery of a healthy child at 35 weeks of gestation.

PMID- 19770792
TI  - Antibiotics for the treatment of primary sclerosing cholangitis.
AB  - Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease that
      is associated with considerable morbidity and mortality. The disease
      etiopathogenesis has not been well defined. Several observations suggest that
      portal bacteremia or chronic bile duct infection may be factors that could play a
      role in the pathogenesis of the disease. Clinical trials have tested different
      treatments for PSC but without convincing evidence of benefit. Liver
      transplantation is the only available therapeutic option that is thought to be
      beneficial for PSC. Antibiotics have been used in several case series over the
      years to treat PSC and have had, in some cases, impressive benefits when compared
      with other drugs used for treating the disease. We gathered the available data
      for different antibiotics used in PSC in this review. Further studies are needed
      to support the efficacy of using antibiotics for PSC patients.

PMID- 19770793
TI  - Safety and efficacy of prolonged use of unfractionated heparin after percutaneous
      coronary intervention.
AB  - The current guidelines for percutaneous coronary intervention do not address the
      prolonged postprocedural use of unfractionated heparin (UFH) to prevent acute
      occlusion. However, recently published small studies have yielded mixed results,
      leaving the question unanswered. Hence, we performed a meta-analysis of the
      existing evidence to assess the safety and efficacy of prolonged infusion of UFH
      after percutaneous coronary intervention. A systematic review of literature
      revealed seven studies involving 2412 patients. End points analyzed were ischemic
      complications (acute closure, myocardial infarction, and repeat
      revascularization) and major vascular complications (hematoma, arteriovenous
      fistula, pseudoaneurysm, and retroperitoneal bleed). Because the studies were
      homogenous for outcomes, combined relative risks across all the studies and the
      95% confidence intervals were computed using the Mantel-Haenszel fixed-effect
      model. A two-sided alpha error <0.05 was considered to be statistically
      significant. There were no significant differences in patient demographics
      between both groups. Compared with placebo, the risk of major vascular
      complication was significantly higher in patients getting postprocedural UFH for
      prolonged hours (relative risk, 2.24; confidence interval, 1.68-3.48; P = 0.001).
      However, the risk of ischemic complications was similar in both groups (relative
      risk, 0.95; confidence interval, 0.46-1.96; P = 0.89). The meta-analysis suggests
      that routine infusion of UFH after uncomplicated percutaneous coronary
      intervention may result in increased vascular complications without any reduction
      in incidence of ischemic complications.

PMID- 19770794
TI  - Switching from atorvastatin to simvastatin in patients at high cardiovascular
      risk: effects on low-density lipoprotein cholesterol.
AB  - Since generic simvastatin became available in the United States in 2006,
      approximately one million patients have switched from atorvastatin to
      simvastatin. We examined the association between switching from atorvastatin to
      simvastatin and changes in low-density lipoprotein cholesterol (LDL-C) levels in
      clinical practice. We compared atorvastatin-treated patients at high
      cardiovascular risk who switched to simvastatin between June 2006 and July 2007
      with randomly selected matched patients who remained on atorvastatin and
      evaluated changes in LDL-C and percentage of patients reaching LDL-C less than
      100 mg/dL. Of patients who switched from atorvastatin to simvastatin, the
      majority were excluded as a result of lack of LDL-C measurements, leaving 383
      patients in the analysis. Among these, 122 (31.9%) switched to a simvastatin dose
      that was less than therapeutically equivalent to their prior atorvastatin dose.
      Compared with control subjects, switched patients were less likely to reach an
      LDL-C less than 100 mg/dL (68.4% versus 74.0%; odds ratio, 0.76; 95% confidence
      interval, 0.59-0.99; P = 0.041) and had higher measured LDL-C (91.4 versus 87.2
      mg/dL; P = 0.009). Switched patients who were not prescribed a higher milligram
      dose of simvastatin were significantly less likely to reach an LDL-C less than
      100 mg/dL (62.3% versus 74.0%; odds ratio, 0.55; 95% confidence interval, 0.36
      0.84; P = 0.006) and had higher LDL-C (95.1 versus 87.2 mg/dL; P = 0.002) than
      control subjects. A large proportion of patients who switch from atorvastatin to
      simvastatin are prescribed doses that are not therapeutically equivalent, and
      these patients were significantly less likely to meet LDL-C treatment goals
      compared with patients who remained on atorvastatin.

PMID- 19770795
TI  - High-dose cyclophosphamide for moderate to severe refractory multiple sclerosis:
      2-year follow-up (investigational new drug No. 65863).
AB  - High-dose cyclophosphamide (HDC) is a chemotherapy treatment designed to
      eradicate autoreative B- and T-cells responsible for lymphocyte-mediated
      autoimmune illness while sparing the pluripotent blood stem cell of any ill
      effects. Multiple sclerosis (MS) is the most common inflammatory and
      demyelinating immune-mediated disorder of the central nervous system in young
      adults. Patients with moderate to severe, refractory MS, defined as an Expanded
      Disability Status Scale (EDSS) score of 3.5 or higher after two or more Food and
      Drug Administration-approved disease-modifying agents, received 200 mg/kg of
      cyclophosphamide over 4 days. For the next 2 years, quarterly EDSS score
      evaluations and biannual brain magnetic resonance imaging and neuro
      ophthalmologic evaluations were obtained. Fifteen patients were evaluated for
      clinical response. During follow-up, one patient increased their baseline EDSS
      score by 1.0. EDSS score stability of decrease was realized in five of seven
      (71%) patients with relapsing-remitting MS and six of eight (75%) patients with
      secondary progressive MS. Four patients required additional immunomodulatory
      treatment after treatment. Treatment response was seen regardless of the baseline
      presence or absence of contrast lesion activity. HDC can effectively decrease
      symptoms, stop disease progression, and allow for disability regression in
      relapsing-remitting MS and secondary progressive MS patients. The most
      appropriate candidates for HDC, its duration of benefit, and the potential need
      for prophylactic preventative immune manipulation after HDC all require further
      investigation.

PMID- 19770796
TI  - Effect of ethanol on the release of morphine sulfate from Oramorph SR tablets.
AB  - Recent data have shown that rapid release of active drug (i.e., dose-dumping) can
      occur when modified-release formulations of pain medications, and other extended
      release pharmacotherapies, are exposed to ethanol in vitro. Dose-dumping of
      sustained-release opioids is of particular concern because of the risk for
      serious and potentially fatal adverse events. Sustained-release morphine sulfate
      tablets (Oramorph SR, 15, 30, 60, and 100 mg; Xanodyne Pharmaceuticals, Inc.,
      Newport, KY) were incubated in vitro at simulated physiologic conditions in media
      containing no ethanol or ethanol in concentrations ranging from 4%-40% v/v.
      Morphine sulfate release was measured over the course of 1 to 24 hours using a
      high-performance liquid chromatography method (United States Pharmacopeia). The
      sustained-release morphine sulfate tablets exhibited no evidence of active drug
      dose-dumping. Regardless of ethanol concentration, ethanol exposure did not
      increase the rate of release of morphine sulfate. Release of approximately 20%
      25% of the morphine sulfate dose within 1 hour was consistent among the morphine
      doses tested and ethanol concentrations. Release of morphine sulfate from the 60-
      and 100-mg tablets exposed to the higher ethanol concentrations (20% and 40%
      ethanol) was slightly delayed at all time points beyond 1 hour. The results of
      this in vitro study suggest that ethanol concentrations as high as 40% do not
      substantially alter the sustained-release properties of the morphine sulfate
      tablets.

PMID- 19770797
TI  - Effects of FX06 in vitro on platelet, coagulation, and fibrinolytic biomarkers in
      volunteers and patients with documented coronary artery disease.
AB  - FX06 is a naturally occurring fibrin-derived peptide demonstrated to confer
      cytoprotection in the setting of primary percutaneous coronary intervention.
      Because the effect of FX06 on human platelet, coagulation, and fibrinolysis
      biomarkers (PCFB) is unknown but is important for further clinical development,
      we evaluated how FX06 affects PCFB. The in vitro effects of the whole-blood pre
      incubation with escalating concentrations of FX06 (4, 25, and 75 MUg/mL) were
      assessed in aspirin-naive healthy volunteers (n = 10), those with multiple risk
      factors for vascular disease (n = 10), and patients with documented coronary
      artery disease (n = 10). The last two groups were treated with aspirin (81
      mg/daily). Thirty-two variables of PCFB were measured with the vehicle and for
      each chosen FX06 dose. Pretreatment of blood samples with FX06 resulted in a
      moderate but significant and mostly dose-dependent increases of platelet
      aggregation induced by adenosine diphosphate and collagen. Similarly, the closure
      time was reduced, suggesting share-induced activation, PECAM-1, GP Ib, GP
      IIb/IIIa activity, and vitronectin receptors, which were also up-regulated. In
      contrast, P-selectin and GPIIb antigen expression were reduced after FX06. All
      other PCFB were predominantly unaffected by FX06, with the exception of the
      increased plasminogen, decreased protein C activity, and activated von Willebrand
      factor. We conclude that in the therapeutic range, FX06 in vitro mildly affects
      hemostasis by way of mostly activating platelets. Applying moderate concomitant
      antiplatelet strategies should be considered for the adequate protection from
      vascular thrombotic events in patients treated with FX06. Similar ex vivo study
      in patients receiving aspirin and clopidogrel is warranted. 

PMID- 19770798
TI  - Cardiac output measurement by arterial pressure waveform analysis during
      optimization of biventricular pacing after cardiac surgery.
AB  - Biventricular pacing (BiVP) can optimize cardiac output (CO) in patients after
      cardiac surgery, so devices that calculate continuous CO from arterial pressure
      may be a useful tool. We investigated PulseCO for measuring CO during
      optimization by comparison with aortic flow probe measurement. Seven patients in
      the Biventricular Pacing After Cardiac Surgery (BiPACS) trial were studied.
      Before weaning from cardiopulmonary bypass, BiVP was initiated. After bypass, CO
      was optimized by varying atrioventricular pacing delay, ventricular site, and
      interventricular pacing delay with a randomized protocol. Continuous CO was
      measured by PulseCO and aortic flow probe. Reliability was estimated by Fleiss
      method and agreement assessed by Bland-Altman analysis. Compared with flow probe,
      PulseCO reliably measured changes in CO (intraclass correlation coefficient =
      0.90) but underestimated the change (-4% + or - 17%). In contrast, changes in
      mean arterial pressure did not reflect changes in CO (intraclass correlation
      coefficient = 0.02). Thus, PulseCO can measure continuous CO in open-chest
      patients after cardiac surgery, whereas underestimating changes occurring across
      10-second pacemaker changes. Further studies in the closed chest are indicated.

PMID- 19770799
TI  - A passively suspended Tesla pump left ventricular assist device.
AB  - The design and initial test results of a new passively suspended Tesla type left
      ventricular assist device blood pump are described. Computational fluid dynamics
      (CFD) analysis was used in the design of the pump. Overall size of the prototype
      device is 50 mm in diameter and 75 mm in length. The pump rotor has a density
      lower than that of blood and when spinning inside the stator in blood it creates
      a buoyant centering force that suspends the rotor in the radial direction. The
      axial magnetic force between the rotor and stator restrain the rotor in the axial
      direction. The pump is capable of pumping up to 10 L/min at a 70 mm Hg head rise
      at 8,000 revolutions per minute (RPM). The pump has demonstrated a normalized
      index of hemolysis level below 0.02 mg/dL for flows between 2 and 9.7 L/min. An
      inlet pressure sensor has also been incorporated into the inlet cannula wall and
      will be used for control purposes. One initial in vivo study showed an
      encouraging result. Further CFD modeling refinements are planned and endurance
      testing of the device.

PMID- 19770800
TI  - Use of extracorporeal membrane oxygenation for adults in cardiac arrest (E-CPR):
      a meta-analysis of observational studies.
AB  - Published data on the use of extracorporeal membrane oxygenation (ECMO) as a
      supportive measure during or immediately after cardiopulmonary resuscitation
      (CPR) in adults (older than 18 years) shows mixed results. To assess the clinical
      outcomes of the use of ECMO in this modality and to look for predictors of
      mortality, we performed a meta-analysis (MA) of individual patients collected
      from observational studies. An electronic PubMed search restricted to English
      language publications between 1990 and 2007, using a consensus restrictive
      criterion, retrieved 141 titles. After full text evaluation, 11 clinical series
      and nine case reports were considered appropriate and included in our MA. Data on
      135 individually identified adult patients (male:female = 1.6:1) were collected.
      Median age for the group was 56 years (range 18-83), and the median ECMO run was
      54 hours (range 0-3881). Overall survival to hospital discharge was 40% (54 of
      135). The most common diagnosis leading to cardiac arrest was acute myocardial
      infarction (46 of 135 patients). Compared with the youngest group (17-41 years),
      odds ratio (OR) for mortality was higher for age group 41-56 years (OR 2.9 95%;
      CL, 1.6-8.2) and those older than 67 years (OR 3.4%; 95% CL, 1.2-9.7). Duration
      of ECMO support measured in days was also a predictor of mortality, with
      significant better outcome for those supported between 0.875 and 2.3 days (OR
      0.2; 95% CL, 0.07-0.6). There was a negative trend in survival when manual CPR
      lasted >30 minutes without prompt ECMO initiation (OR 1.9; 95% CL, 0.9-4.2). This
      work confirms the expectations for a better survival when E-CPR is used in
      younger patients, for shorter periods of time and after expeditious
      implementation during or immediately after manual CPR. Neurologic sequelae and
      other major complications, although suspected to be high, are poorly described in
      the reviewed literature.

PMID- 19770801
TI  - Organ donation after cardiac determination of death (DCD): a swine model.
AB  - Donors after Cardiac Death (DCD) may reduce the organ scarcity; however, their
      use is limited because of warm ischemia time. Fortunately, this is less important
      in a subclass of DCD called expected (e-DCD), those with irreversible but
      incomplete brain injury. This study analyzed hemodynamic/pulmonary data to
      establish a clinically relevant model of cardiac death that would simulate an e
      DCD setting. Hemodynamics, pulmonary artery flows, arterial blood gasses, and
      left atrial pressure were recorded q 5 minutes in anesthetized swine. After
      baseline data collection, the ventilator was discontinued and heparin was
      administered. Cardiac death was defined: as asystole, or mean arterial presusure
      < or = 25 mm Hg with a pulse pressure < or = 20 mm Hg. The time to death was
      approximately 14.8 minutes. Within 5 minutes of removal of the ventilator, there
      was a hyperdynamic period. Blood gases throughout the apneic time showed a rapid
      hypercapnia and acidosis. The hyperdynamic reflex response was followed by
      hypotension, bradycardia, and finally asystole or ventricular fibrillation. The
      protocol of withdrawal of ventilation, systemic anticoagulation, determination of
      death was developed to closely resemble the clinical e-DCD scenario. The
      physiologic changes that happen before death in DCD were described. An e-DCD
      model that can be used in studies related to organ transplantation was
      established.

PMID- 19770802
TI  - Pooled nucleic acid testing to identify antiretroviral treatment failure during
      HIV infection.
AB  - BACKGROUND: Pooling strategies have been used to reduce the costs of polymerase
      chain reaction-based screening for acute HIV infection in populations in which
      the prevalence of acute infection is low (less than 1%). Only limited research
      has been done for conditions in which the prevalence of screening positivity is
      higher (greater than 1%). METHODS AND RESULTS: We present data on a variety of
      pooling strategies that incorporate the use of polymerase chain reaction-based
      quantitative measures to monitor for virologic failure among HIV-infected
      patients receiving antiretroviral therapy. For a prevalence of virologic failure
      between 1% and 25%, we demonstrate relative efficiency and accuracy of various
      strategies. These results could be used to choose the best strategy based on the
      requirements of individual laboratory and clinical settings such as required
      turnaround time of results and availability of resources. CONCLUSIONS: Virologic
      monitoring during antiretroviral therapy is not currently being performed in many
      resource-constrained settings largely because of costs. The presented pooling
      strategies may be used to significantly reduce the cost compared with individual
      testing, make such monitoring feasible, and limit the development and
      transmission of HIV drug resistance in resource-constrained settings. They may
      also be used to design efficient pooling strategies for other settings with
      quantitative screening measures.

PMID- 19770803
TI  - Diagnosis and monitoring of HIV-1 group O-infected patients in Cameroun.
AB  - OBJECTIVE: To define a routine algorithm for the specific diagnosis and complete
      follow-up of HIV-1 group O (HIV-O) infections in Cameroun. METHODS: During 18
      months, samples referred to Centre Pasteur du Cameroun for HIV testing or viral
      monitoring were screened for HIV-O infection with an in-house serotyping assay.
      HIV-O viral load was quantified by real-time polymerase chain reaction in the LTR
      gene and resistance genotyping was performed on pol and env sequences. RESULTS:
      Of the 7030 samples tested, 78 HIV-O infections (1.1%) were identified, including
      7 M and O dually seroreactive samples (9%). All treatment-naive patients and 59%
      of the patients receiving HAART had detectable viral loads. Analysis of pol
      sequences from 15 treatment-naive patients revealed a high number of
      polymorphisms in the protease region, with natural residues implicated in
      genotypic resistance to tipranavir and saquinavir for HIV-1 group M according to
      the Agence Nationale de Recherches sur le Sida et les Hepatites virales
      algorithm. Six patients (40%) harbored the 181C mutation conferring natural
      resistance to nonnucleoside reverse transcriptase inhibitors. Among
      antiretroviral-treated patients, major resistance mutations described for HIV-1
      group M were found. CONCLUSIONS: HIV-O prevalence remains relatively low in
      Cameroun. The cocirculation of groups M and O in this country leads to
      replicative dual infections. HIV-O-infected patients in this region can now
      benefit from effective and specific tools for a complete monitoring of infection.
      However, further studies are needed to understand long-term response to
      antiretrovirals of these complex variants.

PMID- 19770805
TI  - The Montana cardiac rehabilitation regional outcomes project.
AB  - PURPOSE: Outcomes evaluation is a critical component in early outpatient cardiac
      rehabilitation (CR). The goal of this project was to develop a regional CR
      outcomes program to help facilitate quality improvement. METHODS: The Montana
      Outcomes Project initiated data collection on a uniform set of outcomes
      indicators. Each participating program submitted de-identified data for analysis
      on a quarterly basis. Results were sent back to each program with its individual
      program data plotted against the regional mean. RESULTS: Year 1 data collection
      included outcomes information from 22 facilities and 850 patients. Mean age was
      68 years, 96% were white, 68% were men, and the mean number of CR visits was 24.
      The mean resting blood pressure at program completion was 118/68 mm Hg, with 90%
      of patients meeting criteria for blood pressure control (<140/90 or <130/80 mm Hg
      for patients at high risk). Mean low-density lipoprotein was 87 mg/dL; 94% were
      on lipid-lowering medications; and 73% achieved low-density lipoprotein values of
      less than 100 mg/dL. Upon program completion, significant improvements (P < .001)
      were noted in prescore versus postscore for functional capacity measured by the
      Duke Activity Status Index (5.5 metabolic equivalents vs 7.3 metabolic
      equivalents), Medical Outcomes Study SF-36 Health Status Questionnaire physical
      (36.9 vs 45.8) and mental (47.2 vs 52.2) composite scores, Dartmouth Primary Care
      Cooperative questionnaire (22 vs 15.9), and fat intake measured by the Block
      Dietary Fat Screener (19.6 vs 14.7). CONCLUSION: Our findings suggest that the
      development of a regional CR outcomes project is feasible and could aid in the
      development of quality improvement projects.

PMID- 19770804
TI  - A meta-analysis of the incidence of non-AIDS cancers in HIV-infected individuals.
AB  - OBJECTIVE: To estimate summary standardized incidence ratios (SIRs) of non-AIDS
      cancers among HIV-infected individuals compared with general population rates
      overall and stratified by gender, AIDS, and highly active antiretroviral therapy
      (HAART) era. DESIGN: A meta-analysis using SIRs from 18 studies of non-AIDS
      cancer in HIV-infected individuals. METHODS: SIRs for non-AIDS cancers in HIV
      infected individuals and 95% confidence limits (CLs) were abstracted from each
      study. Random effects meta-analyses were used to estimate summary SIRs.
      Modifications by gender, AIDS, and HAART era were estimated with meta-regression.
      RESULTS: Four thousand seven hundred ninety-seven non-AIDS cancers occurred among
      625,716 HIV-infected individuals. SIRs for several cancers were elevated. In
      particular, cancers associated with infections, such as anal (SIR = 28; 95% CL 21
      to 35), liver (SIR = 5.6; 95% CL 4.0 to 7.7), and Hodgkin lymphoma (SIR = 11; 95%
      CL 8.8 to 15) and smoking, such as lung (SIR = 2.6; 95% CL 2.1 to 3.1), kidney
      (SIR = 1.7; 95% CL 1.3 to 2.2), and laryngeal (SIR = 1.5; 95% CL 1.1 to 2.0).
      AIDS was associated with greater SIRs for Hodgkin lymphoma, leukemia, lung,
      brain, and all non-AIDS cancers combined. CONCLUSIONS: HIV-infected individuals
      may be at an increased risk of developing non-AIDS cancers, particularly those
      associated with infections and smoking. An association with advanced immune
      suppression was suggested for certain cancers.

PMID- 19770806
TI  - Physical exercise improves the peripheral microcirculation of patients with
      chronic heart failure.
AB  - PURPOSE: Patients with chronic heart failure (CHF) present with microcirculation
      alterations, partially attributed to endothelial dysfunction. Exercise training
      has been shown to induce beneficial effects in CHF patients. The aim of our study
      was to assess the effect of physical exercise on the microcirculation of CHF
      patients by near-infrared spectroscopy (NIRS). METHODS: Sixteen consecutive
      stable CHF patients (men, n = 10; mean age = 50 +/- 12 years) participated in a 3
      month rehabilitation program (3 sessions per week). All patients performed
      symptom-limited, ramp-incremental cardiopulmonary exercise testing on a cycle
      ergometer before and after the completion of the program. Measurements included
      peak oxygen uptake (VO2peak), VO2 at anaerobic threshold (AT), and first-degree
      slope of VO2 during the first minute of recovery (VO2/t slope). Tissue oxygen
      saturation was continuously measured by NIRS at the thenar muscle during a 3
      minute vascular occlusion with a pneumatic cuff (occlusion technique) before and
      after the rehabilitation program. RESULTS: The oxygen reperfusion rate (%/min)
      following the release of vascular occlusion increased significantly after the
      rehabilitation program (450 +/- 105 to 532 +/- 151, P = .004) as did vascular
      reactivity (from 27 +/- 13%/min to 39 +/- 21%/min, P = .006). In addition, there
      was a significant increase in VO2peak and AT (from 14.3 +/- 4.7 mL . kg . min to
      16.7 +/- 6.3 mL . kg . min and from 9.5 +/- 3.6 mL . kg . min to 11.3 +/- 4 mL .
      kg . min, P = .007 and P = .012, respectively) as well as in VO2/t slope (from
      0.35 +/- 0.17 to 0.51 +/- 0.07 mL . kg . min, P = .005). CONCLUSIONS: Peripheral
      microcirculation of CHF patients measured by NIRS improved after the
      rehabilitation program. NIRS is a noninvasive technique that could be used to
      evaluate the effect of rehabilitation on the peripheral microcirculation of CHF
      patients.

PMID- 19770807
TI  - Pain threshold is achieved at intensity above anaerobic threshold in patients
      with intermittent claudication.
AB  - PURPOSE: Walking training is considered as the first treatment option for
      patients with peripheral arterial disease and intermittent claudication (IC).
      Walking exercise has been prescribed for these patients by relative intensity of
      peak oxygen uptake (VO2peak), ranging from 40% to 70% VO2peak, or pain threshold
      (PT). However, the relationship between these methods and anaerobic threshold
      (AT), which is considered one of the best metabolic markers for establishing
      training intensity, has not been analyzed. Thus, the aim of this study was to
      compare, in IC patients, the physiological responses at exercise intensities
      usually prescribed for training (% VO2peak or % PT) with the ones observed at AT.
      METHODS: Thirty-three IC patients performed maximal graded cardiopulmonary
      treadmill test to assess exercise tolerance. During the test, heart rate (HR),
      VO2, and systolic blood pressure were measured and responses were analyzed at the
      following: 40% of VO2peak; 70% of VO2peak; AT; and PT. RESULTS: Heart rate and
      VO2 at 40% and 70% of VO2peak were lower than those at AT (HR: -13 +/- 9% and -3
      +/- 8%, P < .01, respectively; VO2: -52 +/- 12% and -13 +/- 15%, P < .01,
      respectively). Conversely, HR and VO2 at PT were slightly higher than those at AT
      (HR: +3 +/- 8%, P < .01; VO2: +6 +/- 15%, P = .04). None of the patients achieved
      the respiratory compensation point. CONCLUSION: Prescribing exercise for IC
      patients between 40% and 70% of VO2peak will induce a lower stimulus than that at
      AT, whereas prescribing exercise at PT will result in a stimulus above AT. Thus,
      prescribing exercise training for IC patients on the basis of PT will probably
      produce a greater metabolic stimulus, promoting better cardiovascular benefits.

PMID- 19770808
TI  - Patient and program outcome assessment in pulmonary rehabilitation: an AACVPR
      statement.
AB  - Quantifying and analyzing pulmonary rehabilitation (PR) results in the form of an
      outcome assessment are a means of evaluating patient performance and program
      effectiveness. Implementation of a structured outcome assessment is feasible and
      parallels many aspects of the traditional rehabilitation evaluation. This
      statement outlines key components to PR outcome evaluation in the context of the
      American Association of Cardiovascular and Pulmonary Rehabilitation PR Outcome
      Matrix and includes a discussion of some of the popular tools used to collect
      measurement data.

PMID- 19770809
TI  - In vivo confocal microscopy of the palpebral conjunctiva and tarsal plate.
AB  - PURPOSE: The aim of this work is to develop a more complete understanding of the
      in vivo histology of the human palpebral conjunctiva and tarsal plate. METHODS:
      The upper eyelids of 11 healthy human volunteer subjects were everted, and laser
      scanning confocal microscopy was used to examine the various tissue layers of the
      palpebral conjunctiva and tarsal plate. RESULTS: The superficial and basal
      epithelial layers are composed of cells with gray cytoplasm and thick, light gray
      borders. Nuclei can not be seen. The stroma has a varied appearance; fibrous
      tissue is sometimes observed, interspersed with dark, amorphous lacunae, and
      crevases. Numerous single white or gray cells populate this tissue, and fine
      blood vessels are seen traversing the field. Occasional conjunctival microcysts
      and Langerhans cells are observed. The tarsal plate is dark and amorphous, and
      meibomian gland acini with convoluted borders are clearly observed. Acini are
      composed of an outer lining of large cuboidal cells, and differentiated secretory
      cells can be seen within the acini lumen. CONCLUSIONS: Laser scanning confocal
      microscopy is capable of studying the human palpebral conjunctiva, tarsal plate,
      and acini of meibomian glands in vivo. The observations presented here may
      provide useful supplementary anatomical information relating to the morphology of
      this tissue.

PMID- 19770810
TI  - Tear physiology of aqueous deficiency and evaporative dry eye.
AB  - PURPOSE: To determine the differences in tear physiology between aqueous
      deficiency dry eye (ADDE) and evaporative dry eye (EDE), and evaluate their
      utility in diagnosis. METHODS: Fifty-six dry eye patients were classified into 30
      ADDE and 26 EDE according to the recently published Dry Eye Workshop criteria. A
      range of tear physiology measures comprising of tear evaporation, turnover rate
      (TTR), distribution, volume and osmolarity, and meibomian gland dropout were
      measured in these patients. The effectiveness of the tests, singly and in
      combinations, in differentiating between the dry eye subtypes was evaluated by
      retrospective allocation into groups and by Receiver Operative Characteristics
      (ROC) curve analysis. RESULTS: Statistically significant differences were seen
      for TTR and tear evaporation (with lower values for ADDE) between ADDE and EDE,
      but no significant differences were seen for tear osmolarity, volume,
      distribution, and meibomian gland dropout scores. Differentiation of ADDE and EDE
      by a cut-off value of 11%/min for TTR was found to have a sensitivity of 86%,
      specificity of 75%, positive predictive value 89%, negative predictive value 69%,
      and overall accuracy 83%. The area under the curve on the ROC curve was 0.83. For
      tear evaporation, a cut-off of 60 g/mh was found to have a sensitivity of 77%,
      specificity of 55%, positive predictive value 38%, negative predictive value 80%,
      and overall accuracy 58% in subtype differentiation. The area under the curve was
      0.59 on the ROC curve. The distribution curve of the evaporation rates for ADDE
      and EDE, showed an overlap coefficient of 0.76 indicating that tear evaporation
      is within a similar range in these two dry eye subtypes. CONCLUSIONS: Tear
      turnover is significantly lower in ADDE than EDE, but there is considerable
      overlap of tear evaporation between the two dry eye subtypes. Tear osmolarity and
      turn over tests can be conducted sequentially to effectively diagnose dry eye and
      its subtypes.

PMID- 19770811
TI  - Ex vivo protein deposition on bi-weekly silicone hydrogel contact lenses.
AB  - PURPOSE: This study investigated the protein deposition that occurs on daily wear
      silicone hydrogel (SH) lenses, after 2 weeks of wear. METHODS: A total of 40
      subjects were divided into equal groups, based on their habitual SH contact lens
      [CIBA Vision O2OPTIX (O2); Johnson & Johnson ACUVUE ADVANCE with HYDRACLEAR
      (ADV); Bausch & Lomb PureVision (PV); CIBA Vision Night & Day (ND)]. A
      randomized, double-masked, cross-over study was conducted in which subjects wore
      either their habitual SH material or Johnson & Johnson ACUVUE OASYS with
      HYDRACLEAR PLUS (OAS) for 2 weeks. At the end of the 2-week period, lenses were
      collected for analysis of total protein, total lysozyme, and percent denatured
      lysozyme. RESULTS: Total protein was greatest for PV (33 +/- 6 microg/lens), with
      other lenses depositing <10 microg/lens. The PV amount was greater than other
      materials (p < 0.001), with no significant differences between the other three
      materials (p > 0.05). Total lysozyme was also greatest for the PV lens (11 +/- 3
      microg/lens), with other lenses depositing <2 microg/lens. The PV amount was
      greater than all other materials (p < 0.001). ADV and OAS were greater than O2 (p
      < 0.01) but were not different from each other (p > 0.05). The percentage of
      lysozyme that was denatured was greatest for ND (90 +/- 8%) and lowest for PV (23
      +/- 10%). The lysozyme extracted from ND and O2 lenses was significantly more
      denatured than that extracted from the other lens materials (p < 0.001). There
      were no significant differences for lysozyme activity between ND and O2 (p >
      0.05) or between ADV, OAS, and PV (p > 0.05). The amount of denatured
      lysozyme/lens was <3 microg/lens for all materials. Lysozyme as a percentage of
      the total protein deposited ranged from 32 (PV) to 6% (O2). CONCLUSIONS: This
      study confirms that all SH lenses deposit low levels of protein, and that the
      amount and percentage of denatured lysozyme can vary, depending on the overall
      surface charge of the material and absence or type of surface treatment.

PMID- 19770812
TI  - The perceived bulbar redness of clinical grading scales.
AB  - PURPOSE: To use a psychophysical scaling method to estimate the perceived redness
      of reference images of the McMonnies and Chapman-Davies (six reference levels),
      Institute for Eye Research (four), Efron (five), and Validated Bulbar Redness
      (five) bulbar redness grading scales. METHODS: Regions of interest were cropped
      out of the grading scale reference images; three separate image sets (color,
      grayscale, and binarized) were created for each scale, combining to a total of 20
      images per image set. Ten naive observers were asked to arrange printed copies of
      the 20 images per image set across a distance of 1.5 m on a flat surface, so that
      separation reflected their perception of bulbar redness; only start and end point
      of this range were indicated. The position of each image was averaged across
      observers to represent the perceived redness for this image, within the 0 to 100
      range. Subjective data were compared with physical attributes (chromaticity and
      spatial metrics) of redness. RESULTS: For each image set, perceived redness of
      the reference images within each scale was ordered as expected, but not all
      consecutive within-scale levels were rated as having different redness. Perceived
      redness of the reference images varied between scales, with different ranges of
      severity being covered by the images. Perception of redness severity depended on
      the image set (repeated-measures analysis of variance; all p < or = 0.0002). The
      perceived redness was strongly associated with the physical attributes of the
      reference images. CONCLUSIONS: Subjective estimates of redness are based on a
      combination of chromaticity and vessel-based components. Psychophysical scaling
      of perceived redness lends itself to being used to cross-calibrate these four
      clinical scales.

PMID- 19770813
TI  - Predicting state anxiety in optometric practice.
AB  - PURPOSE: Patient anxiety has been shown to be detrimental to healthcare
      consultations and their outcomes. To date, little is known about the causes of
      patient anxiety in optometric practice. Therefore, the purpose of this study was
      to identify the predictors of state anxiety for patients attending optometric
      consultations. METHODS: Three hundred sixty six participants (127 male, 239
      female; mean age, 54.5; SD +/- 18.0) took part in the study. Each participant
      completed a preconsultation questionnaire including established measures of
      "state" anxiety, "trait" anxiety, study specific outcome expectancies, and
      biographical data. Multiple linear regression analysis was used to identify which
      variables predict state anxiety. RESULTS: Multiple linear regression analysis
      showed that the heightened trait anxiety, expecting "bad news" and being a non
      spectacle wearer are independent predictors of increased state anxiety. R was
      0.33, i.e., the regression model explained 33% of the variance. CONCLUSIONS: This
      is the first time that the predictors of state anxiety in optometric practice
      have been identified. Optometrists should recognize that patients who are
      "anxious types," who may be expecting "bad news" and who do not wear spectacles
      may be more anxious.

PMID- 19770815
TI  - First U.S. near-total human face transplantation: a paradigm shift for massive
      complex injuries.
AB  - BACKGROUND: Severe complex facial injuries are difficult to reconstruct and
      require multiple surgical procedures. The potential of performing complex
      craniofacial reconstruction in one surgical procedure is appealing, and composite
      face allograft transplantation may be considered an alternative option. The
      authors describe establishment of the Cleveland Clinic face transplantation
      program that led them to perform the first U.S. near-total face transplantation.
      METHODS: In November of 2004, the authors received the world's first
      institutional review board approval to perform a face transplant in humans. In
      December of 2008, after a 22-hour operation, the authors performed the first near
      total face transplantation in the United States, replacing 80 percent of the
      patient's traumatic facial deficit with a composite allograft from a brain-dead
      donor. This largest, and most complex, face allograft in the world included over
      535 cm2 of facial skin; functional units of full nose with nasal lining and bony
      skeleton; lower eyelids and upper lip; underlying muscles and bones, including
      orbital floor, zygoma, maxilla, alveolus with teeth, hard palate, and parotid
      glands; and pertinent nerves, arteries, and veins. Immunosuppressive treatment
      consisted of thymoglobulin, tacrolimus, mycophenolate mofetil, and prednisone.
      RESULTS: The patient tolerated the procedure and immunosuppression well. At day
      47 after transplantation, routine biopsy showed rejection of the graft mucosa
      without clinical evidence of skin or graft rejection. The patient's physical and
      psychological recovery went well. The functional outcome has been excellent,
      including optimal return of breathing through the nose, smelling, tasting,
      speaking, drinking from a cup, and eating solid foods. CONCLUSION: The functional
      outcome thus far at 8 months is rewarding and confirms the feasibility of
      performing complex reconstruction of severely disfigured patients in a single
      surgical procedure of facial allotransplantation.

PMID- 19770814
TI  - Receding and disparity cues aid relaxation of accommodation.
AB  - PURPOSE: Accommodation can mask hyperopia and reduce the accuracy of non
      cycloplegic refraction. It is, therefore, important to minimize accommodation to
      obtain a measure of hyperopia as accurate as possible. To characterize the
      parameters required to measure the maximally hyperopic error using
      photorefraction, we used different target types and distances to determine which
      target was most likely to maximally relax accommodation and thus more accurately
      detect hyperopia in an individual. METHODS: A PlusoptiX SO4 infra-red
      photorefractor was mounted in a remote haploscope which presented the targets.
      All participants were tested with targets at four fixation distances between 0.3
      and 2 m containing all combinations of blur, disparity, and proximity/looming
      cues. Thirty-eight infants (6 to 44 weeks) were studied longitudinally, and 104
      children [4 to 15 years (mean 6.4)] and 85 adults, with a range of refractive
      errors and binocular vision status, were tested once. Cycloplegic refraction data
      were available for a sub-set of 59 participants spread across the age range.
      RESULTS: The maximally hyperopic refraction (MHR) found at any time in the
      session was most frequently found when fixating the most distant targets and
      those containing disparity and dynamic proximity/looming cues. Presence or
      absence of blur was less significant, and targets in which only single cues to
      depth were present were also less likely to produce MHR. MHR correlated closely
      with cycloplegic refraction (r = 0.93, mean difference 0.07 D, p = n.s., 95%
      confidence interval +/-<0.25 D) after correction by a calibration factor.
      CONCLUSIONS: Maximum relaxation of accommodation occurred for binocular targets
      receding into the distance. Proximal and disparity cues aid relaxation of
      accommodation to a greater extent than blur, and thus non-cycloplegic refraction
      targets should incorporate these cues. This is especially important in screening
      contexts with a brief opportunity to test for significant hyperopia. MHR in our
      laboratory was found to be a reliable estimation of cycloplegic refraction.

PMID- 19770816
TI  - Tracking dynamics of muscle engraftment in small animals by in vivo fluorescent
      imaging.
AB  - Muscular dystrophies are a group of degenerative muscle diseases characterized by
      progressive loss of contractile muscle cells. Currently, there is no curative
      treatment available. Recent advances in stem cell biology have generated new
      hopes for the development of effective cell based therapies to treat these
      diseases. Transplantation of various types of stem cells labeled with fluorescent
      proteins into muscles of dystrophic animal models has been used broadly in the
      field. A non-invasive technique with the capability to track the transplanted
      cell fate longitudinally can further our ability to evaluate muscle engraftment
      by transplanted cells more accurately and efficiently. In the present study, we
      demonstrate that in vivo fluorescence imaging is a sensitive and reliable method
      for tracking transplanted GFP (Green Fluorescent Protein)-labeled cells in mouse
      skeletal muscles. Despite the concern about background due to the use of an
      external light necessary for excitation of fluorescent protein, we found that by
      using either nude mouse or eliminating hair with hair removal reagents much of
      this problem is eliminated. Using a CCD camera, the fluorescent signal can be
      detected in the tibialis anterior (TA) muscle after injection of 5 x 10(5) cells
      from either GFP transgenic mice or eGFP transduced myoblast culture. For more
      superficial muscles such as the extensor digitorum longus (EDL), injection of
      fewer cells produces a detectable signal. Signal intensity can be measured and
      quantified as the number of emitted photons per second in a region of interest
      (ROI). Since the acquired images show clear boundaries demarcating the engrafted
      area, the size of the ROI can be measured as well. If the legs are positioned
      consistently every time, the changes in total number of photons per second per
      muscle and the size of the ROI reflect the changes in the number of engrafted
      cells and the size of the engrafted area. Therefore the changes in the same
      muscle over time are quantifiable. In vivo fluorescent imaging technique has been
      used primarily to track the growth of tumorogenic cells, our study shows that it
      is a powerful tool that enables us to track the fate of transplanted stem cells.

PMID- 19770817
TI  - [Surgical treatment of metastatic lung lesions: state of art].
AB  - 454 patients, aged 17-79 years, were operated on metastatic lung lesions during
      the period from 1970 to 2007 years. Overall 538 operations were performed, of
      them 40 bilateral lung resections, 33 patients were reoperated on the subject of
      recurrent lung metastases. Postoperative complications were registered in 44
      (9,6%) patients. Lethality rate was 1,1%. Overall 5-year survival after solitary
      metastasis removal was 34,9+/-3,1%, after removal of several lesions the survival
      rate was 21,7+/-4,8%, and after operation on the subject of multiple lung
      metastasis the survival rate was 14,7+/-4,5%. The level of intrathoracic lymph
      nodes involvement and type of the performed surgery showed to be independent
      prognostic factors.

PMID- 19770818
TI  - [Surgical access for small-sized lung lesions].
AB  - Experience of diagnostics and surgical treatment of of 100 patients with small
      sized lung lesions was analyzed. Thus, authors pose, that patients with lung
      focal lesion less than 10mm in diameter, should have a lung resection, performed
      from minithoracotomy. Videthotacoscopic lung biopsy is appropriate by multiple
      focal lesions. Patients with solitary peripheral lung lesion more than 1sm in
      diameter, should get a lung resection, performed from minithoracotomy with
      videoassistance. Patients with solitary lesion less than 5 mm in diameter requier
      radiological dynamic follow-up (CT-scan each 6 months).

PMID- 19770819
TI  - [Is local prosthetics of descending thoracic aorta by its distal dissection
      effective?].
AB  - 12 patients with distal aortic dissection were included in the study. All had
      aortic prosthetics and hemodynamic correction. 6 patients (1st group) had
      hemodynamic correction type I - Cutdown of the false aortic canal and guiding the
      blood flow to the correct canal. The rest 6 (2nd group) hemodynamic correction
      type II was performed (guiding blood flow to the both aortic channels). 83,3% of
      patients of the 1st group demonstrated the false aortic channel thrombosis up to
      the level of visceral branches, the rest 33,3% of patients had total thrombosis
      of the false channel. All patients of the 2nd group demonstrated maintenance of
      the blood flow in both channels, which leaves risk of further aortic dilatation
      and rupture.

PMID- 19770820
TI  - [Automatic blood reinfusion in intraabdominal bleedings].
AB  - 147 patients with polytrauma, complicated by acute large-volume intraabdominal
      bleeding, were included in the study. Anesthetic regimens and blood loss
      compensation were retrospectively analyzed. Thus, all patints were divided inti 3
      groups: 1st group received only intraoperative blood reinfusion, 2nd group - got
      auto- and donor blood reinfusion, 3rd group had only donor blood transfusions.
      Intraoperative autoblood reinfusion allowed an adequate blood loss compensation.
      The method should be considered a method of choice by acute blood loss treatment
      during emergency operations in patients with polytrauma.

PMID- 19770821
TI  - [Diagnostics and surgical treatment of solid pseudopapillary pancreas tumors].
AB  - Solid-pseudopapillary pancreatic tumors (SPPT) are slow-growing tumors and have a
      considerably good prognosis, in case of radical removal. Thus, results of
      surgical treatment of 10 patients with SPPT were analyzed. On the basis of
      ultrasound examination, computed tomography, magnetic resonance imaging and
      intraoperative picture 2 groups of patients were formed. 1st group consisted of 3
      patients and was characterized by small tumor diameter (2,5-5 sm) and solid
      structure. The rest 7 patients formed the 2nd group; tumor was larger (more than
      5 sm) and had a cystic structure. Radiologic features of SPPT were: cystic
      component of the tumor (especially with papillary structures), hemorragic
      contents of the cysts, capsule and calcinates both in stroma and capsule.
      Magnetic resonance imaging proved to be the most effective diagnostic method. All
      patients with solid-pseudopapillary carcinomas of pancreas had adjuvant
      chemotherapy. At present all patients are in satisfactory state.

PMID- 19770822
TI  - [Pancreatic stump preparation by pancreatoduodenal resection].
AB  - Short-term results of 124 pancreatoduodenal resections (PDR) are analyzed. 65,3%
      of patients had pancreatic cancer, 12,1% - cancer of the papilla Vateri, 3,2% -
      cancer of the terminal part of the common bile duct, 2,4% - cancer of the
      duodenum, 2,4% carcinoid of the pancreas, 14,5% - chronic pancreatitis with the
      affection og the head. Standard Whipple procedure performed in 91 patients,
      pyloro-saving PDR - in 32 cases and total pancreatoduodenectomy in one patient. 3
      types of pancreatic stump preparation were used. Pancreatojejunal anastomosis
      (PEA) (n=63) considered to be the first, pancreatogastroanastomosis (PGA) (n=46 )
      - the second and external pancreaticostomy (n=15) - the third. Overall
      anastomosis failure rate was 12,1% (n=15). By PEA, failure rate was 27,5% and was
      noticed predominately in cases of connecting all area of pancreatic slice with
      the gut (43,5%). PGA failure rate was 2,1% (n=1). Therefore, PDA should be
      considered to be a reliable pancreatodigestive anastomosis, allowing a decrease
      of postoperative complication rate to 26,1% and lethality rate to 2,1%.

PMID- 19770823
TI  - [Comparative analysis of treatment modes of acute ezophago-gastric bleedings in
      patients with portal hypertension].
AB  - 40 years' experience of treatment of acute ezophago-gastric bleedings in patients
      with portal hypertension is analyzed. In dependence of the treatment trends,
      three periods of of time were assigned. The 1st period was characterized by
      surgical treatment nonmetering clinical features. Second period combined a more
      differential approach with the use of rational conservative means. The 3rd period
      was characterized by the destroy of the specialized surgical help, but introduced
      a range of mini-invasive procedures, which allowed a fivefold decrease of
      lethality.

PMID- 19770824
TI  - [Surgical treatment of esophageal cancer].
AB  - Prospective study, included 117 patients with esophageal cancer, all received
      resection of the esophagus through laparatomy and and right-side thoracotomy
      without neoadjuvant chemotherapy. 70,0% of patients demonstrated stage higher
      then IIb UICC. R0 resection was possible in 101 patients (86,3%). Hospital
      lethality was 5,1%. Overall lethality among the operated patients was 21,4%. Long
      term follow-up results were obtained in 96,6%. Surgical treatment alone does not
      provide satisfactory results for the patients with cancer of esophagus. Further
      therapy individualization and combination of surgery with modern neoadjuvant
      chemotherapy can provide better prognosis for these patients.

PMID- 19770825
TI  - [Surgical treatment of rectovaginal fistulae].
AB  - Results of treatment of 31 patients, aged 22-62 years, with rectovaginal fistula
      (RVG) were analyzed. RVG of the 1st degree of complexity was found in 7 patients;
      19 women had RVG of the 2nd degree of complexity and the rest 5 patients had an
      RVG of the 3rd degree. During the surgery bringing down mucosa, the so called
      "tissue flap plasty" with the anterior sphincterolevatoroplasty was performed.
      Low-intensity laser irradiation was used for wound treatment postoperatively.
      Fistula recurrence was registered only in two patients.

PMID- 19770826
TI  - [Initial precipitating injury and symptomatic focal epilepsies].
AB  - A study included 793 epileptic patients. Symptomatic epilepsy caused by initial
      precipitating injury (IPI) was diagnosed in 151 cases. Evaluation of anamnesis,
      clinical and neurological examination, routine EEG and/or video-EEG-monitoring
      and MRI of the brain were carried out. Period of observation was 6 months - 5
      years (on average 3 years). Age of IPI was reversely correlated with duration of
      latent period (LP). High frequency of seizures was correlated with poor
      effectiveness of treatment. Different types of IPI differed by frequency of
      seizures, duration of LP and effectiveness of treatment.

PMID- 19770827
TI  - [Clinical and molecular genetic diagnosis of leukoencephalopathy with brainstem
      and spinal cord involvement and lactate elevation in children].
AB  - Leukoencephalopathy with brainstem and spinal cord involvement and lactate
      elevation (LBSL) is a recently described disorder with autosomal recessive model
      of inheritance. Mutations in the DARS2 gene, which encode mitochondrial aspartyl
      tRNA synthetase, have been found. We present 31 cases with characteristic
      clinical and neuroimaging findings of this disorder. Patients have been
      stratified into two groups (early and late forms) by age-at-onset and clinical
      symptoms. The early form was characterized clinically by progressive pyramidal
      dysfunction, cerebellar and intellectual problems appeared later. Patients with
      the late form had cerebellar and sensitive ataxia, disturbances of muscle tonus,
      spastic type, mostly in the low extremities, polyneuropathic and rarely -
      psychoorganic syndrome. The brain MRI of all patients was characterized by
      inhomogeneous T2W signal abnormalities in the periventricular and deep white
      matter and a strikingly selective involvement of certain brainstem and spinal
      tracts. Most of the patients were compound-heterozygous for common mutations in
      the DARS2. We found 4 new mutations associated with LBSL. This is the first
      clinical and molecular-genetic investigation of this rare leukoencephalopathy in
      Russia.

PMID- 19770828
TI  - [Fatigability in Parkinson's disease].
AB  - Forty-five patients with Parkinson's disease (PD) without dementia were studied.
      Duration of disease was 6,02+/-3,47 years. The following scales were used: PFS
      16, UPDRS part 2, the Beck Depression Scale, PDSS and the Epworth Sleepiness
      Scale. Fatigability is thought to be one of three presentations of PD that
      restrict daily activities in 64% of patients. The integrated assessment of
      fatigability was significantly correlated with the total depression score and
      PDSS scores. The treatment with mirapex resulted in the reduction of fatigability
      that was not correlated with changes in motor functioning, depression, sleep
      disorders. Fatigability is a symptom that significantly disturbs daily activities
      of patients. The author suggests that fatigability is more associated with
      nervous and psychiatric symptoms than with a severity of movement disorders. The
      lack of significant association between dynamics of fatigability and changes in
      other parameters of nervous and psychiatric functions during the therapy
      plausibly implies the separate genesis of this symptom.

PMID- 19770829
TI  - [Mental disorders in patients admitted for cataract surgery].
AB  - An aim of the present study was to clinically evaluate mental changes in patients
      admitted for extracapsular cataract extraction. Eighty patients (27 male and 53
      female), mean age 72,2+/-7,2 years, were studied. A clinical-psychopathological
      examination was conducted. Type of disease attitude, Eysenck neuroticism and
      psychoticism scores, Taylor anxiety and Beck depression levels mere studied
      before and after the surgery. Most of patients - 56 (70%) had mental disorders in
      the pre-surgery period. They were stratified into 3 groups by syndromes. Twenty
      seven patients (33,7%) had asthenic-depressive disorders, 16 (20%) - anxiety
      phobic disorders and 13 (16,2%) - anxiety-depressive disorders. These disorders
      disappeared after the surgery in most patients. The greater stability of
      psychopathological appearances was characteristic of patients with anxiety
      depressive symptoms. These patients also demonstrated personality changes (the
      higher level of neuroticism).

PMID- 19770830
TI  - [Influence of cerebrolysin therapy on the dynamics of diabetic polyneuropathy
      symptoms].
AB  - 60 patients with clinical features of symmetric diabetic polyneuropathy have been
      examined including 30 patients of main group who received cerebrolysin and 30
      patients of control group treated with milgamma. The effectiveness of treatment
      was assessed by the dynamics of polyneuropathic disorders in scores on the
      Diabetic polyneuropathy scale and the NDS. Pain syndrome was measured with the
      VAS. The significant therapeutic effectiveness of cerebrolysin was revealed for
      some parameters measured.

PMID- 19770831
TI  - [Cavinton in the complex treatment of patients with chronic cerebrovascular
      insufficiency].
AB  - A complex clinical-instrumental study included 138 patients with discirculatory
      encephalopathy (DE) who received cavinton perorally in dose 30 mg/day during 90
      days (2 courses in a year) in addition to the basic therapy (hypotensive and
      antithrombotic drugs, neuroprotector glycine). A control group comprised 98
      patients clinically matched with the main group. They received only basic
      therapy. Neurological status and results of neuropsychological tests were
      assessed before treatment and to the end of 3, 6 and 12 months. The improvement
      of all neurological syndromes studied was seen in the main group to the end of 12
      months as compared to controls. The complex treatment using cavinton led to the
      significant decrease of risk of DE progression, development of transitory
      ischemic attacks and strokes compared to controls (relative risks were 0,01 and
      0,14, respectively).

PMID- 19770832
TI  - [Psychosomatic inductions in a family and their correction by a psychotherapist].
AB  - Twelve mother-child pairs with common somatic-neurological symptoms have been
      examined. A clinical-psychological examination of women revealed increased levels
      of anxiety, hypochondria, physical and verbal aggression. Suggestion from a
      mother and imitation by a child characteristic of mother-child pairs cause
      psychosomatic inductions. The theoretical basis for the treatment of this type of
      frustrations are a synergetic conceptions on family as an open system. The
      treatment has been conducted in two stages. In the first stage, a mother received
      the hypnosuggestive psychotherapy (HSPT), along with the complex treatment with
      somatotrophic and psychotropic drugs, to work out specific hypnotic states. In
      the second stage, a child with psychosomatic symptoms underwent HSPT sessions in
      the presence of his/her mother. The effectiveness of treatment was 91,7% in
      children and 75% - in mothers.

PMID- 19770833
TI  - [The use of topiramate at patients with combined craniovertebral anomaly].
AB  - Twenty-eight patients with concomitant cranio-vertebral anomaly: Kimmerle anomaly
      and Chiari type I malformation were examined. A main reason for visiting a doctor
      was headache, dizziness and sleep disturbance. Topamax (topiramate) was used for
      stopping the symptoms. It was prescribed in dosage 25 mg in the evening to 16
      patients and in dosage 25 mg in the first two weeks and then in dosage 50 mg in
      the evening for 60 days - to 12 patients. The use of Topamax led to the reduction
      and /or disappearance of headache, sleep normalization and improvement of
      cerebral bioelectric activity. The drug was well tolerated.

PMID- 19770834
TI  - [Comparative assessment of MR-semiotics of acutest intracerebral hematomas in low
      and extra high-field frequency magnetic resonance tomography].
AB  - An objective of the study was to compare sensitivity of low- and extra high-field
      frequency magnetic resonance (MR) tomography of acutest intracerebral hematomas
      (ICH) and to assess differences between symptoms in obtained images. A study was
      conducted using experimental ICH in rats (n=6). Hematomas were formed by two
      injections of autologic blood into the brain. MR-devices "Bio Spec 70/30" with
      magnetic field strength of 7 T and "Ellipse-150" with magnetic field strength of
      0,15 T were used in the study. MR-tomography was carried out 3-5 h after the
      injections. Both MR-devices revealed the presence of pathological lesion in all
      animals. Extra highfield frequency MR-tomography showed the specific signs of ICH
      caused by the paramagnetic effect of deoxyhemoglobin in T2 and T2*-weighted
      images (WI) and low frequency MR-tomography - in T2*-WI only. The comparable
      sensitivity of low- and extra high-field frequency MR-devices in acutest ICH was
      established.

PMID- 19770835
TI  - [Vasomotor innervation of the human pia mater in arterial hypertension].
AB  - Materials of forensic-medical autopsies of men, aged 18-44 year, who died from
      trauma, have been studied. Arteries of the pia mater have been taken from 26 men
      with arterial hypertension (AH), stages I-III, and 12 men without AH.
      Histochemical methods have been used to study the structure of nerve plexus of
      medial brain artery branches of different diameters. In AH, there were changes of
      the nerve plexus structure in brain arterial branches, the intensity of which was
      related to the vessel diameter and disease stage; the decrease of density of
      periadventicial adrenergic nerve plexus compared to controls, which was most
      intensive in AH, stage I, and in the vessels of smaller size. The changes in
      concentration of distinctly seen bulges (varicosities) were more significant
      compared to those of nervous fibers. The effectiveness of nitrooxidergic
      innervation was also decreased in large vessels and its structure did not visibly
      change in small arterial branches. In conclusion, there is a formation of
      vasomotor innervation dysfunction in AH.

PMID- 19770836
TI  - [Indicators of the spontaneous B-lymphocytes proliferation in diagnostics of
      neurological signs of rheumatoid arthritis].
AB  - An aim of the paper was to study indicators of the spontaneous B-lymphocytes
      proliferation activity (SBLPA) in patients with rheumatoid arthritis (RA) and
      lesions of the nervous system. Fifty-eight patients with neurological symptoms of
      RA were studied. A comparison group included 42 patients with RA without lesions
      of the nervous system. A control group consisted of 30 healthy people. The
      investigation of SBLP was conducted using a method of R. Rigler in the
      modification of E.V. Benenson et al. Significant between-group differences allow
      to conclude that indicators of SBLP can be used for diagnostics of nervous system
      lesions in RA.

PMID- 19770837
TI  - [The Cys allele of the DRD2 (Ser311Cys polymorphism) is associated with
      schizophrenia and worse sustained attention in patients].
AB  - The DRD2 Ser311Cys polymorphism was studied in a sample which included 366
      patients with schizophrenia and 387 healthy controls. The frequency of the Cys
      allele was significantly higher (p<0,009) in the group of patients compared to
      the controls (8,5% and 3,9%, respectively). Sustained attention assessed by P300
      parameters was studied in 66 patients with the SerSer and SerCys genotypes (the
      CysCys genotype was not observed in the sample studied). A significant effect
      (p=0,01) of the SerCys genotype on P300 latency in frontal, central and temporal
      regions was found. Patients with the at-risk allele presented delayed latencies
      that reflected the lower speed of mental processes related to activation of
      attention resources. In conclusion, our data support the evidence of association
      between the Cys allele and schizophrenia obtained earlier for other populations
      and revealed that carriers of the genotype containing the at-risk allele had
      delayed P300 latencies.

PMID- 19770839
TI  - Overexpression of endoplasmic reticulum protein 29 regulates mesenchymal
      epithelial transition and suppresses xenograft tumor growth of invasive breast
      cancer cells.
AB  - Endoplasmic reticulum protein 29 (ERp29) is a novel endoplasmic reticulum (ER)
      secretion factor that facilitates the transport of secretory proteins in the
      early secretory pathway. Recently, it was found to be overexpressed in several
      cancers; however, little is known regarding its function in breast cancer
      progression. In this study, we show that the expression of ERp29 was reduced with
      tumor progression in clinical specimens of breast cancer, and that overexpression
      of ERp29 resulted in G(0)/G(1) arrest and inhibited cell proliferation in MDA-MB
      231 cells. Importantly, overexpression of ERp29 in MDA-MB-231 cells led to a
      phenotypic change and mesenchymal-epithelial transition (MET) characterized by
      cytoskeletal reorganization with loss of stress fibers, reduction of fibronectin
      (FN), reactivation of epithelial cell marker E-cadherin and loss of mesenchymal
      cell marker vimentin. Knockdown of ERp29 by shRNA in MCF-7 cells reduced E
      cadherin, but increased vimentin expression. Furthermore, ERp29 overexpression in
      MDA-MB-231 and SKBr3 cells decreased cell migration/invasion and reduced cell
      transformation, whereas silencing of ERp29 in MCF-7 cells enhanced cell
      aggressive behavior. Significantly, expression of ERp29 in MDA-MB-231 cells
      suppressed tumor formation in nude mice by repressing the cell proliferative
      index (Ki-67 positivity). Transcriptional profiling analysis showed that ERp29
      acts as a central regulator by upregulating a group of genes with tumor
      suppressive function, for example, E-cadherin (CDH1), cyclin-dependent kinase
      inhibitor (CDKN2B) and spleen tyrosine kinase (SYK), and by downregulating a
      group of genes that regulate cell proliferation (eg, FN, epidermal growth factor
      receptor (EGFR) and plasminogen activator receptor (uPAR)). It is noteworthy that
      ERp29 significantly attenuated the overall ERK cascade, whereas the ratio of p
      ERK1 to p-ERK2 was highly increased. Taken together, our results showed that
      ERp29 is a novel regulator leading to cell growth arrest and cell transition from
      a proliferative to a quiescent state, and reprogramming molecular portraits to
      suppress the tumor growth of MDA--MB--231 breast cancer cells.

PMID- 19770838
TI  - Highly active antiretroviral therapy drugs inhibit in vitro cholesterol efflux
      from human macrophage-derived foam cells.
AB  - We previously reported that HIV protease inhibitor, ritonavir, could inhibit
      cholesterol efflux and induce endothelial dysfunction. In this study, we further
      determined the effects and molecular mechanisms of a clinically relevant
      combination of highly active antiretroviral therapy (HAART) drugs on in vitro
      cholesterol efflux from human macrophage-derived foam cells. Foam cells derived
      from human monocyte cell line (THP-1) and periphery blood mononuclear cells
      (PBMCs) treated with HAART drugs including stavudine, didanosine and indinavir
      individually or in combination of three drugs (3-plex), followed by the
      initiation of cholesterol efflux with apolipoprotein A-I (apoA-I). Clinically
      relevant concentrations of HAART 3-plex significantly reduced cholesterol efflux
      in foam cells derived from THP-1 and PBMCs. HAART 3-plex significantly reduced
      the intracellular cholesterol transport molecule caveolin-1, whereas it increased
      superoxide anion production in THP-1 foam cells as compared with controls.
      Furthermore, mitochondrial membrane potential was significantly reduced, whereas
      the expression of NADPH oxidase subunit p67(phox) was increased in HAART 3-plex
      treated macrophages. Consequently, antioxidants including ginsenosides Rb1 and
      Rg1, S-allyl cysteine sulphoxide (SACS), simvastatin (SVT) and vitamin E
      significantly abolished HAART 3-plex-induced inhibition of cholesterol efflux.
      Therefore, HAART drugs significantly inhibit cholesterol efflux from human
      macrophage-derived foam cells through downregulation of caveolin-1 and increase
      of oxidative stress.

PMID- 19770840
TI  - Intracellular versus extracellular granzyme B in immunity and disease:
      challenging the dogma.
AB  - The cytotoxic granzyme B (GrB)/perforin pathway has been traditionally viewed as
      a primary mechanism that is used by cytotoxic lymphocytes to eliminate
      allogeneic, virally infected and/or transformed cells. Although originally
      proposed to have intracellular and extracellular functions, upon the discovery
      that perforin, in combination with GrB, could induce apoptosis, other potential
      functions for this protease were, for the most part, disregarded. As there are 5
      granzymes in humans and 11 granzymes in mice, many studies used perforin knockout
      mice as an initial screen to evaluate the role of granzymes in disease. However,
      in recent years, emerging clinical and biochemical evidence has shown that the
      latter approach may have overlooked a critical perforin-independent, pathogenic
      role for these proteases in disease. This review focuses on GrB, the most
      characterized of the granzyme family, in disease. Long known to be a pro
      apoptotic protease expressed by cytotoxic lymphocytes and natural killer cells,
      it is now accepted that GrB can be expressed in other cell types of immune and
      nonimmune origin. To the latter, an emerging immune-independent role for GrB has
      been forwarded due to recent discoveries that GrB may be expressed in nonimmune
      cells such as smooth muscle cells, keratinocytes, and chondrocytes in certain
      disease states. Given that GrB retains its activity in the blood, can cleave
      extracellular matrix, and its levels are often elevated in chronic inflammatory
      diseases, this protease may be an important contributor to certain pathologies.
      The implications of sustained elevations of intracellular and extracellular GrB
      in chronic vascular, dermatological, and neurological diseases, among others, are
      developing. This review examines, for the first time, the multiple roles of GrB
      in disease pathogenesis.

PMID- 19770842
TI  - An inosine 5'-monophosphate dehydrogenase 2 single-nucleotide polymorphism
      impairs the effect of mycophenolic acid.
AB  - Mycophenolic acid (MPA) is a selective inhibitor of inosine 5'-monophosphate
      dehydrogenase (IMPDH), the rate-limiting enzyme of de novo synthesis of guanine
      nucleotides. The isoenzyme IMPDH2 predominates in activated lymphocytes, and its
      inhibition by MPA is part of standard immunosuppressive regimens. Yet, there are
      significant unexplained differences in efficacy and tolerability among patients.
      The objective of this study was to analyze whether frequent variants in the
      IMPDH2 gene lead to changes in IMPDH activity and to differences in
      responsiveness to MPA therapy. All 14 exons and intron-exon boundary regions of
      IMPDH2 were sequenced from genomic DNA probes from 100 healthy individuals. Two
      novel exonic single-nucleotide polymorphisms were identified in 1% and one
      intronic polymorphism (rs11706052) in 19% of the study population. Lymphocyte
      IMPDH activity and proliferation under three MPA concentrations (2.5, 10 and 25
      micromol l(-1)) were compared in rs11706052 carriers and wild-type individuals.
      The presence of rs11706052 polymorphism reduced the antiproliferative effect of
      MPA on lymphocytes by approximately 50% compared with the IMPDH2 wild-type form
      at therapeutic relevant concentrations of 10 micromol l(-1) and 25 micromol l(
      1). We conclude that a poorer response to MPA therapy can be explained in some
      individuals by the presence of the rs11706052 polymorphism.

PMID- 19770843
TI  - Can residents perform transrectal ultrasound-guided prostate biopsy with patient
      comfort comparable to biopsy performed by attending staff urologists?
AB  - Transrectal ultrasound (TRUS)-guided prostate biopsy is a critical diagnostic
      tool in urology. Residents require adequate training but resident education could
      have a deleterious effect on patient comfort and morbidity. We compared pain
      associated with prostate biopsy when performed by staff versus resident
      urologists in order to determine the impact of resident training. Male patients
      scheduled to undergo prostate biopsy were assigned to either a staff urologist or
      a resident as the primary surgeon. All residents were directly assisted by the
      staff surgeon. The patients were given a visual analogue scale (VAS; 0-100 mm)
      and were asked to assess the pain associated with each component of prostate
      biopsy, including probe insertion, anesthetic injection and the biopsies
      themselves. The mean VAS scores for probe insertion, anesthetic injection and
      biopsies were 31.0, 30.4 and 30.1, respectively, for patients in the staff cohort
      and 37.1, 28.9 and 33.6, respectively, for those in the resident cohort. There
      was a statistically significant difference between staff and resident VAS scores,
      marked by a higher odds of greater pain with ultrasound probe placement (odds
      ratio (OR)=1.48, P=0.012) and the biopsies themselves (OR=1.52, P=0.01) in the
      resident cohort. TRUS biopsy can be performed by adequately trained and
      supervised resident urologists of all levels, but there is the potential for
      increased patient pain, particularly with ultrasonic probe insertion and
      obtaining core biopsies. However, the absolute magnitude of the differences in
      pain scores between residents and staff was small and may not be clinically
      meaningful. Such data indicate that urological resident training can be
      accomplished without compromising patient care and comfort.

PMID- 19770845
TI  - A systematic evaluation of the compatibility of histones containing methyl-lysine
      analogues with biochemical reactions.

PMID- 19770844
TI  - Fas stimulation of T lymphocytes promotes rapid intercellular exchange of death
      signals via membrane nanotubes.
AB  - The Fas/CD95 surface receptor mediates rapid death of various cell types,
      including autoreactive T cells with the potential for triggering autoimmunity.
      Here, we present novel aspects of Fas signalling that define a 'social' dimension
      to receptor-induced apoptosis. Fas stimulation rapidly induces extensive membrane
      nanotube formation between neighbouring T cells. This is critically dependent on
      Rho GTPases but not on caspase activation. Bidirectional transfer of membrane and
      cytosolic elements including active caspases can be observed to occur via these
      nanotubes. Nanotube formation and intercellular exchanges of death signals are
      defective in T lymphocytes from patients with autoimmune lymphoproliferative
      syndrome harbouring mutations in the Fas receptor. We conclude that nanotube
      mediated exchanges constitute a novel form of intercellular communication that
      augments the propagation of death signalling between neighbouring T cells.

PMID- 19770846
TI  - Why are oseltamivir and zanamivir effective against the newly emerged influenza A
      virus (A/H1N1)?

PMID- 19770847
TI  - Endoscopic and pathological aspects of colitis-associated dysplasia.
AB  - The risk of developing colorectal cancer in patients with colitis-associated
      dysplasia is considerable. Surveillance programs in patients with ulcerative
      colitis and Crohn's disease aim to detect dysplastic lesions early and rely
      heavily on taking random biopsy samples along the length of the colon. Diagnosing
      dysplasia can be difficult because of the heterogeneous endoscopic appearance of
      dysplasia and the poor interobserver agreement among pathologists when grading
      dysplasia. Colitis-associated dysplasia may present as a dysplasia-associated
      lesion or mass (DALM), which may be indistinguishable from a sporadic adenoma in
      non-colitic tissue, or may arise in flat mucosa of endoscopically normal
      appearance. Information about the endoscopic appearance, the colonic distribution
      and the histopathological grade of colitis-associated dysplasia is required to
      define the optimal treatment. This Review summarizes the endoscopic and
      histopathological features of colitis-associated dysplasia and the requirements
      for optimal interaction between endoscopists and pathologists, with the aim of
      reducing the uncertainties in the diagnosis of dysplastic lesions and improving
      the management of colitis-associated dysplasia.

PMID- 19770849
TI  - Near vacuum ultraviolet luminescence of Gd3+ and Er3+ ions generated by super
      saturation upconversion processes.
AB  - Near vacuum ultraviolet (UV) upconversion (UC) emissions with a spectral
      resolution of 1 nm, from the (6)G(J), (6)D(J), (6)I(J), (6)P(J) levels of Gd(3+)
      and the (2)L(17/2), (4)D(7/2), (2)H(2)(9/2), (2)D(5/2), (4)G(7/2), (2)K(13/2),
      (2)P(3/2) levels of Er(3+), were observed under 974 nm laser excitation.
      Mechanism analyses illustrate that successive energy transfers (ETs) from Yb(3+)
      to Er(3+) generate UV UC radiations in Er(3+), while two resonant ETs from Er(3+)
      to Gd(3+) lead to UV UC radiations in Gd(3+). Power dependence analyses indicate
      that the expected inefficient four- and five-photon processes have been switched
      into efficient two-photon processes due to a super saturation UC phenomenon that
      employs consecutive saturations at the intermediate states.

PMID- 19770850
TI  - Improvement of modulation bandwidth in multisection RSOA for colorless WDM-PON.
AB  - We demonstrated two-section reflective semiconductor optical amplifier (RSOA)
      with dramatic improvement of small-signal modulation bandwidth above 10 GHz as
      colorless source for wavelength division multiplexed-passive optical network (WDM
      PON). The device provides the fiber-to-fiber gain of 22.8 dB, 3-dB amplified
      spontaneous emission (ASE) bandwidth of 30 nm, and ripple of 1.5 dB. Good
      performance at 2.5 Gbps was obtained with an extinction ratio of 8 dB and a power
      penalty of 2 dB at a 10(-9) bit error rate (BER) up to 20 km transmission.

PMID- 19770851
TI  - K-shell x-ray emission enhancement via self-guided propagation of intense laser
      pulses in Ar clusters.
AB  - K-shell x-ray at about 3 keV emitted from Ar clusters irradiated by 110 mJ 55 fs
      intense laser pulses is studied. The x-ray flux is optimized by moving the nozzle
      away from the focus of the laser pulse. The total flux of K-shell x-ray photons
      in 4pi reaches a maximum of 4.5x10(9) photons/shot with a conversion efficiency
      of 2.5x10(-5) when the nozzle displacement is 2 mm and a long plasma channel is
      observed by a probe beam.

PMID- 19770852
TI  - High-flux and broadband biphoton sources with controlled frequency entanglement.
AB  - We report the high-flux and broadband generation of biphotons with controlled
      frequency entanglement. For the generation of the entangled state consisting of
      frequency-anticorrelated photons, we use PPMgSLT pumped by a continuous-wave (cw)
      laser. Meanwhile, the state consisting of frequency-correlated photons is
      produced from PPKTP under the extended phase-matching condition. Both states
      exhibited interference patterns with over 90% visibilities in two-photon
      interference experiments.

PMID- 19770853
TI  - Large-mode-area ytterbium-doped fiber amplifier with distributed narrow spectral
      filtering and reduced bend sensitivity.
AB  - A large-mode area polarization maintaining single-mode ytterbium-doped fiber
      amplifier with distributed narrow passband filtering is demonstrated. The fiber
      passband is 40 nm wide and centered at 1070 nm for efficient filtering of both
      short- and long-wavelength amplified spontaneous emission as well as stimulated
      raman scattering and four-wave-mixing. The fiber shows reduced bend sensitivity,
      has a mode field diameter of 27 microm and exhibits a slope efficiency of more
      than 65%.

PMID- 19770848
TI  - Socioeconomic status and cardiovascular disease: risks and implications for care.
AB  - Socioeconomic status (SES) refers to an individual's social position relative to
      other members of a society. Low SES is associated with large increases in
      cardiovascular disease (CVD) risk in men and women. The inverse association
      between SES and CVD risk in high-income countries is the result of the high
      prevalence and compounding effects of multiple behavioral and psychosocial risk
      factors in people of low SES. However, strong and consistent evidence shows that
      parental SES, childhood and early-life factors, and inequalities in health
      services also contribute to elevated CVD risk in people of low SES who live in
      high-income countries. In addition, place of residence can affect CVD risk,
      although the data on the influence of wealth distribution and work-related
      factors are inconsistent. Studies on the effects of SES on CVD risk in low-income
      and middle-income countries is scarce, but evidence is emerging that the
      increasing wealth of these countries is beginning to lead to replication of the
      patterns seen in high-income countries. Clinicians should address the association
      between SES and CVD by incorporating SES into CVD risk calculations and screening
      tools, reducing behavioral and psychosocial risk factors via effective and
      equitable primary and secondary prevention, undertaking health equity audits to
      assess inequalities in care provision and outcomes, and by use of
      multidisciplinary teams to address risk factors over the life course.

PMID- 19770854
TI  - Optimal laser welding assembly sequences for butterfly laser module packages.
AB  - We present an optimal laser welding assembly sequence for butterfly laser
      packages: 1) initial shift, 2) front welding, 3) rear welding, 4) joint gripper
      releasing, 5) mechanical fine tuning of horizontal misalignment. This sequence
      has been optimized significantly by modeling the initial shift and experimental
      investigations of three assembly sequences. Our results show that misalignment
      from the Post-Weld-Shift (PWS) can be compensated by accurately estimating the
      initial shift in the vertical direction. Furthermore, the laser hammering
      procedure, to compensate for misalignment of the vertical direction, can be
      eliminated by proper package design. Using only final mechanical tuning for
      horizontal misalignments, optical coupling efficiencies of 73-99% have been
      achieved for lasers packaged in butterfly modules.

PMID- 19770855
TI  - Enhanced dispersion compensation capability of angular elements based on beam
      expansion.
AB  - We demonstrate that beam size manipulation plays an important role in dispersion
      compensation. With expanded beam, the maximal negative group delay dispersion
      (GDD) provided by angular elements increases by an order of magnitude compared
      with original beam. Both calculation and experimental results show that a modest
      2 x and 4 x expanded beams can improve dispersion compensation capability of
      prisms or acousto-optical deflectors: the restored minimal pulse width decreases
      by 50% and the corresponding distance between angular elements is shortened more
      than 70 cm. These findings will be helpful for designing dispersion compensation
      schemes for femtosecond pulse laser application systems such as multiphoton
      microscopy or laser micromachining.

PMID- 19770856
TI  - Spectral analysis of phase shifting algorithms.
AB  - Systematic spectral analysis of Phase Shifting Interferometry (PSI) algorithms
      was first proposed in 1990 by Freischlad and Koliopoulos (F&K). This analysis was
      proposed with the intention that "in a glance" the main properties of the PSI
      algorithms would be highlighted. However a major drawback of the F&K spectral
      analysis is that it changes when the PSI algorithm is rotated or its reference
      signal is time-shifted. In other words, the F&K spectral plot is different when
      the PSI algorithm is rotated or its reference is time-shifted. However, it is
      well known that these simple operations do not alter the basic phase demodulation
      properties of PSI algorithms, except for an unimportant piston. Here we propose a
      new way to analyze the spectra of PSI algorithms which is invariant to rotation
      and/or reference time-shift among other advantages over the nowadays standard PSI
      spectral analysis by F&K.

PMID- 19770857
TI  - Self-pinching of pulsed laser beams during filamentary propagation.
AB  - Competing nonlinear optical effects that act on femtosecond laser pulses
      propagating in a self-generated light filament may give rise to a pronounced
      radial beam deformation, similar to the z-pinch contraction of pulsed high
      current discharges. This self-generated spatial beam contraction is accompanied
      by a pulse break-up that can be beneficially exploited for on-axis temporal
      compression of the pulse. The pinching mechanism therefore explains the recently
      observed self-compression and the complicated spatio-temporal shapes typical for
      filament propagation experiments.

PMID- 19770858
TI  - Hybrid GaN/organic microstructured light-emitting devices via ink-jet printing.
AB  - We report what we believe to be the first use of organic nanostructures for
      efficient colour conversion of gallium nitride light emitting diodes (LEDs). The
      particular nanomaterials, based on star-shaped truxene oligofluorenes, offer an
      attractive alternative to inorganic colloidal quantum dots in the search for
      novel and functional 'nanophosphors'. The truxenes have been formed into a
      composite with photoresist and ink-jet printed onto microstructured gallium
      nitride LEDs, resulting in a demonstrator hybrid microdisplay technology with
      pixel size approximately 32 microm. The output power density of the hybrid device
      was measured to be approximately 8.4 mW/cm(2) per pixel at driving current
      density of 870.8A/cm(2) and the efficiency of colour conversion at drive current
      of 7 mA was estimated to be approximately 50%.

PMID- 19770859
TI  - Observation of high-contrast, fast intensity noise of a continuous wave Raman
      fiber laser.
AB  - We investigate the intensity noise of a continuous-wave Raman fiber laser based
      on a novel technique where the noise is sampled with a low repetition rate signal
      in a low walk-off Raman amplifier configuration. With this method, we
      experimentally demonstrate that continuous-wave Raman fiber lasers exhibit high
      contrast intensity fluctuations on a timescale of several tens to hundreds of
      GHz. In fact, the power of the Raman laser fluctuates between nearly zero and a
      high multiple of the average power. Numerical simulations are used to study the
      role of pump depletion on the noise transfer process. Our study validates models
      of pumps used in some recent continuous wave supercontinuum generation
      simulations.

PMID- 19770861
TI  - Plasmon-assisted terahertz imaging inside metal-filled media.
AB  - We present the application of THz plasmonics in imaging dielectric objects
      embedded in metal-filled media. By exploiting the time domain information from
      the transmitted pulse, signatures of the objects were observed. To enhance the
      low quality images acquired through THz time domain spectroscopy, a super
      resolution image processing technique was applied. It is shown that pulse arrival
      time and phase magnitude information compared to the integrated instantaneous
      power of the transmitted pulse provides more detailed images of the embedded
      object.

PMID- 19770860
TI  - Three-dimensional combined photoacoustic and optical coherence microscopy for in
      vivo microcirculation studies.
AB  - Photoacoustic microscopy is predominantly sensitive to optical absorption, while
      optical coherence tomography relies on optical backscattering. Integrating their
      complementary contrasts can provide comprehensive information about biological
      tissue. We have developed a dual-modality microscope that combines the two for
      studying microcirculation. Three-dimensional imaging of microvasculature and its
      local environment has been demonstrated at micrometer-order resolution using
      endogenous contrast in vivo.

PMID- 19770862
TI  - Tuning of whispering gallery modes of spherical resonators using an external
      electric field.
AB  - In this paper we investigate the electrostriction effect on the whispering
      gallery modes (WGM) of polymeric microspheres and the feasibility of a WGM-based
      microsensor for electric field measurement. The electrostriction is the elastic
      deformation (strain) of a dielectric material under the force exerted by an
      electrostatic field. The deformation is accompanied by mechanical stress which
      perturbs the refractive index distribution in the sphere. Both strain and stress
      induce a shift in the WGM of the microsphere. In the present, we develop
      analytical expressions for the WGM shift due to electrostriction for solid and
      thin-walled hollow microspheres. Our analysis indicates that detection of
      electric fields as small as ~500V/m may be possible using water filled, hollow
      solid polydimethylsiloxane (PDMS) microspheres. The electric field sensitivities
      for solid spheres, on the other hand, are significantly smaller. Results of
      experiments carried out using solid PDMS spheres agree well with the analytical
      prediction.

PMID- 19770863
TI  - Characterization of single heat-activated Bacillus spores using laser tweezers
      Raman spectroscopy.
AB  - Heat activation of dormant bacterial spores is a short treatment at a sublethal
      temperature that potentiates and synchronizes spore germination. In this paper,
      laser tweezers Raman spectroscopy (LTRS) was used to study the heat activation of
      single spores of Bacillus cereus and Bacillus subtilis. We measured the Raman
      spectra of single spores without treatment, during heat activation at 65 degrees
      C (B. cereus) or 70 degrees C (B. subtilis), and following heat activation and
      cooling to 25 degrees C. Principle component analysis (PCA) was applied to
      discriminate among the three groups of spores based on their Raman spectra. The
      results indicated that: (1) there are large changes in the Raman bands of Ca-DPA
      and protein for both B. cereus and B. subtilis spores during heat activation,
      indicative of changes in spore core state and partial protein denaturation at the
      heat activation temperatures; (2) these spectral changes become smaller once the
      heated spores are cooled, consistent with heat activation being reversible; (3)
      minor spectral differences between untreated and heat-activated and cooled spores
      can be discriminated by PCA based on non-polarized and polarized Raman spectra;
      and (4) analysis based on polarized Raman spectra reveals that partial
      denaturation of protein during heat activation is mainly observed in the
      vertically polarized component.

PMID- 19770864
TI  - Line-defect calibration for line-scanning projection display.
AB  - A method of line-defect calibration for line-scanning projection display is
      developed to accomplish acceptable display uniformity. The line scanning display
      uses a line modulating imaging and scanning device to construct a two-dimensional
      image. The inherent line-defects in an imaging device and optical lenses are the
      most fatal performance-degrading factor that should be overcome to reach the
      basic display uniformity level. Since the human eye recognizes line defects very
      easily, a method that perfectly removes line defects is required. Most line
      imaging devices are diffractive optical devices that require a coherent light
      source. This particular requirement makes the calibration method of sequential
      single pixel measurement and correction insufficient to take out the line defects
      distributed on screen due to optical crosstalk. In this report, we present a
      calibration method using a recursively converging algorithm that successfully
      transforms the unacceptable line-defected images into a uniform display image.

PMID- 19770865
TI  - Surface plasmon resonance (SPR) sensors: approaching their limits?
AB  - We report on a unified theoretical model of the resolution of SPR sensors which
      makes it possible to predict the ultimate performance of all major configurations
      of SPR sensors. The theory indicates that the performance of SPR sensors is
      independent of the method of excitation of surface plasmons (prism or grating
      coupling) or the method of modulation (amplitude, angular or wavelength) and
      depends dominantly on the noise properties of the light source and detector.
      Results of the theoretical analysis are compared with the performance reported
      for several SPR sensors to illustrate that the best state-of-art SPR sensors are
      approaching their theoretical limits. Possibilities for further advances in the
      performance of SPR sensor technology are discussed.

PMID- 19770866
TI  - Micro/nano scale amorphization of silicon by femtosecond laser irradiation.
AB  - This research aimed to investigate the feasibility of using direct amorphization
      of silicon induced by femtosecond laser irradiation for maskless lithography. A
      thin layer of amorphous silicon of predetermined pattern was first generated by
      irradiation by a femtosecond laser of Mega Hertz pulse frequency. The following
      KOH etching revealed that the amorphous silicon layer acted as an etch stop. Line
      width less than 1/67 the focused spot size was demonstrated and hence the
      proposed maskless lithography process has the potential of producing submicron
      and nanoscale features by employing a laser beam of shorter wavelength and a high
      NA focusing lens. Scanning Electron Microscope (SEM), a Micro-Raman and Energy
      Dispersive X-ray (EDX) spectroscopy analyses were used to evaluate the quality of
      amorphous layer and the etching process.

PMID- 19770867
TI  - Broadband resonant terahertz transmission in a composite metal-dielectric
      structure.
AB  - We present a systematic numerical study of a metal-dielectric-metal sandwich
      plasmonic structure for broadband resonant transmission at terahertz frequencies.
      The proposed structure consists of periodic slotted metallic arrays on both sides
      of a thin dielectric substrate and is demonstrated to exhibit a broad passband
      transmission response. Various design considerations have been investigated to
      exploit their influence on the transmission passband width and the center
      resonance frequency. The structure ensures a broadband transmission over a wide
      range of incident angles.

PMID- 19770868
TI  - Optical lens compression via transformation optics.
AB  - Transformation optics is widely associated with the design of unconventional
      electromagnetic devices, such as electromagnetic cloaks or concentrators.
      However, a wide range of conventional optical devices with potentially
      advantageous properties can be designed by the transformation optical approach.
      For example, a coordinate transformation can be introduced that compresses a
      region of space, resulting in an overall decrease in the thickness of an optical
      instrument such as a lens. The optical properties of a transformed lens, such as
      Fresnel reflection or aberration profile, are equivalent to those of the original
      lens, while the transformed lens and the bounding transformation optical material
      are thinner than the original lens. This approach to flattening the profile of a
      lens represents an advantage over the use of a higher dielectric material because
      it does not introduce greater Fresnel reflections or require a redesign of the
      basic optic. Though transformation optical media are generally anisotropic, with
      both electric and magnetic response, it is possible to arrive at a dielectric
      only transformation optical distribution for a lens interacting with transverse
      magnetic (TM) polarized light. The dielectric-only distribution can be
      implemented using broad-band, low-loss metamaterials. Lens designs for both a
      full transformation and a dielectric-only implementation are discussed and
      confirmed via finite-element simulations.

PMID- 19770869
TI  - Self-mixing interference in fiber ring laser and its application for vibration
      measurement.
AB  - A new approach for self-mixing interference in fiber ring laser and its
      application to vibration measurement is presented. Fourier transform method is
      proposed to improve the measurement accuracy of such an active sensing, in which
      the basic frequency of self-mixing interference signal is used to determine the
      frequency of vibration, and the stop order of the harmonic components is
      proportional to the amplitude of vibration. We have demonstrated this system to
      measure the microscopic vibration of a remote target. Some errors due to this
      method are discussed. The maximum error of the amplitude is about lambda/10 and
      the maximum error of the frequency is about 10%, showing a good agreement with
      the simulative results.

PMID- 19770870
TI  - Resonant normal-incidence separate-absorption-charge-multiplication Ge/Si
      avalanche photodiodes.
AB  - In this work the impedance of separate-absorption-charge-multiplication Ge/Si
      avalanche photodiodes (APD) is characterized over a large range of bias voltage.
      An equivalent circuit with an inductive element is presented for modeling the
      Ge/Si APD. All the parameters for the elements included in the equivalent circuit
      are extracted by fitting the measured S(22) with the genetic algorithm
      optimization. Due to a resonance in the avalanche region, the frequency response
      of the APD has a peak enhancement when the bias voltage is relatively high, which
      is observed in the measurement and agrees with the theoretical calculation shown
      in this paper.

PMID- 19770871
TI  - Continuous wave photon pair generation in silicon-on-insulator waveguides and
      ring resonators.
AB  - Silicon waveguides are promising chi(3)-based photon pair sources. Demonstrations
      so far have been based on picosecond pulsed lasers. Here, we present the first
      investigation of photon pair generation in silicon waveguides in a continuous
      regime. The source is characterized by coincidence measurements. We uncover the
      presence of unexpected noise which had not been noticed in earlier experiments.
      Subsequently, we present advances towards integration of the photon pair source
      with other components on the chip. This is demonstrated by photon pair generation
      in a Sagnac loop interferometer and inside a micro-ring cavity. Comparison with
      the straight waveguide shows that these are promising avenues for improving the
      source. In particular photon pair generation in the micro-ring cavity yields a
      source with a spectral width of approximately 150 pm resulting in a spectral
      brightness increased by more than 2 orders of magnitude.

PMID- 19770872
TI  - Colorless WDM-PON based on a Fabry-Perot laser diode and reflective semiconductor
      optical amplifiers for simultaneous transmission of bidirectional gigabit
      baseband signals and broadcasting signal.
AB  - A novel WDM-PON system delivering bidirectional baseband data and broadcasting
      data is proposed and demonstrated. A subcarrier multiplexing signal is
      broadcasted to all users by modulating a broadband optical source based on a
      Fabry-Perot laser diode. Reflective semiconductor optical amplifiers are used as
      colorless modulators for the baseband data at both optical line terminal and
      remote optical network units. Transmission performance including bit error rate
      of bidirectional gigabit data and error vector magnitude of broadcasting data of
      many optical channels is investigated. Additionally, the data rate for the
      broadcasting signal was improved by using an external modulator.

PMID- 19770873
TI  - Scale-invariant pattern recognition using a combined Mellin radial harmonic
      function and the bidimensional empirical mode decomposition.
AB  - A novel scale and shift invariant pattern recognition method is proposed to
      improve the discrimination capability and noise robustness by combining the
      bidimensional empirical mode decomposition with the Mellin radial harmonic
      decomposition. The flatness of its peak intensity response versus scale change is
      improved. This property is important, since we can detect a large range of scaled
      patterns (from 0.2 to 1) using a global threshold. Within this range, the
      correlation peak intensity is relatively uniform with a variance below 20%. This
      proposed filter has been tested experimentally to confirm the result from
      numerical simulation for cases both with and without input white noise.

PMID- 19770874
TI  - Monte Carlo simulation of polarized photon scattering in anisotropic media.
AB  - We present a Monte Carlo simulation program for the propagation of polarized
      photons in an anisotropic scattering model consisting of poly-dispersed spherical
      and infinite long cylindrical scatterers. The cylinders are aligned following a
      Gaussian distribution. Densities and sizes of the spherical and cylindrical
      scatterers, as well as the orientation of the cylinders are variables for the
      simulation of different anisotropic media. The good agreement between the
      simulation and experimental results of polarization imaging confirms the validity
      of the polarization-dependent Monte Carlo simulation program.

PMID- 19770875
TI  - Control of liquid crystal pretilt angles by using organic/inorganic hybrid
      interpenetrating networks.
AB  - A new photoalignment method of controlling the pretilt angle of liquid crystals
      (LCs) by using organic/inorganic hybrid interpenetrating polymer networks (IPNs)
      is proposed and demonstrated. In the hybrid IPN alignment layer system, the
      competition between poly(vinyl cinnamate) (PVCi) favoring planar alignment and
      poly(dimethyl siloxane) (PDMS) favoring vertical alignment made it possible to
      achieve pretilt angle in a wide range from 0 degrees to 90 degrees, and adjust
      pretilt angle as a function of PDMS content. In addition, we achieved the high
      azimuthal anchoring energy at the intermediate pretilt angle by using PDMS as the
      vertical-aligning component.

PMID- 19770876
TI  - Optical pressure/acoustic sensor with precise Fabry-Perot cavity length control
      using angle polished fiber.
AB  - This paper presents a novel Fabry-Perot (FP) optical fiber pressure/acoustic
      sensor. It consists of two V-shaped grooves having different sized widths, a
      diaphragm on the surface of the larger V-groove, and a 45 degrees angle-polished
      fiber. The precision of FP cavity length is determined by the fabrication process
      of photolithography and anisotropic etching of a silicon crystal. Therefore, the
      cavity length can be controlled on the order of ten nm. Sensors were fabricated
      and tested. Test results indicate that the sensors' cavity lengths have been
      controlled precisely. The packaged sensor has demonstrated very good static and
      dynamic responses compared to a commercially available pressure sensor and a
      microphone.

PMID- 19770877
TI  - Comparative study of the effective single mode operational bandwidth in sub
      wavelength optical wires and conventional single-mode fibers.
AB  - We present the first experimental comparison of effective single mode operation
      bandwidth in sub-wavelength optical wires (SOWs) and conventional single-mode
      fibers (SMFs). The full transmission spectrum, half-turn bend loss and mode field
      diameter were measured and compared for a variety of SMFs of different cut-off
      wavelength and a SOW. The SOW was shown to offer an enormously broadband single
      mode operation bandwidth with a larger mode field area than the SMFs.
      Applications of SOWs include fiber lasers, sensors, photolithography and optical
      coherence tomography amongst others.

PMID- 19770878
TI  - Five beam holographic lithography for simultaneous fabrication of three
      dimensional photonic crystal templates and line defects using phase tunable
      diffractive optical element.
AB  - This paper demonstrates an approach for laser holographic patterning of three
      dimensional photonic lattice structures using a single diffractive optical
      element. The diffractive optical element is fabricated by recording gratings in a
      photosensitive polymer using a two-beam interference method and has four
      diffraction gratings oriented with four-fold symmetry around a central opening.
      Four first-order diffracted beams from the gratings and one non-diffracted
      central beam overlap and form a three-dimensional interference pattern. The phase
      of one side beam is delayed by inserting a thin piece of microscope glass slide
      into the beam. By rotating the glass slide, thus tuning the phase of the side
      beam, the five beam interference pattern changes from face-center tetragonal
      symmetry into diamond-like lattice symmetry with an optimal bandgap. Three
      dimensional photonic crystal templates are produced in a photoresist and show the
      phase tuning effect for bandgap optimization. Furthermore, by integrating an
      amplitude mask in the central opening, line defects are produced within the
      photonic crystal template. This paper presents the first experimental
      demonstration on the holographic fabrication approach of three-dimensional
      photonic crystal templates with functional defects by a single laser exposure
      using a single optical element.

PMID- 19770879
TI  - Chip-scale spectrometry based on tapered hollow Bragg waveguides.
AB  - We describe a micro-spectrometer that exploits out-of-plane radiation at mode
      cutoff in a tapered leaky waveguide clad by omnidirectional Bragg reflectors. The
      device can be viewed as a side-coupled, tapered Fabry-Perot cavity. An effective
      index transfer-matrix model reveals that optimal resolution is dependent on the
      reduction or mitigation of back-reflection and standing waves leading up to the
      cutoff point. We address this by insertion of low numerical aperture optics
      between the taper and the detector, and demonstrate an experimental resolution as
      small as approximately 1 nm and operating bandwidth >100 nm in the 1550 nm range,
      from a tapered waveguide with footprint approximately 50 microm x 500 microm. The
      device combines the small size of a Fabry-Perot instrument with the detector
      array compatibility and fixed optics of a grating-based instrument.

PMID- 19770880
TI  - A silicon-based hybrid plasmonic waveguide with a metal cap for a nano-scale
      light confinement.
AB  - A hybrid plasmonic waveguide with a metal cap on a silicon-on-insulator rib (or
      slab) is presented. There is a low-index material nano-layer between the Si layer
      and the metal layer. The field enhancement in the nano-layer provides a nano
      scale confinement of the optical field (e.g., 50 nm x 5 nm) when operates at the
      optical wavelength lambda = 1550 nm. The theoretical investigation also shows
      that the present hybrid plasmonic waveguide has a low loss and consequently a
      relatively long propagation distance (on the order of several tens of lambda).

PMID- 19770881
TI  - Experimental demonstration of real-time 3Gb/s optical OFDM transceivers.
AB  - Real-time optical orthogonal frequency-division multiplexing (OOFDM) transceivers
      based on off-the-shelf components including FPGAs are experimentally
      demonstrated, for the first time, incorporating key functionalities such as live
      transceiver optimisation and advanced channel estimation, and also utilising self
      developed IFFT/FFT logic algorithms verified at 10 Gb/s. The fastest ever real
      time end-to-end transmission of 3Gb/s DQPSK- and 16-QAM-encoded OOFDM signals
      over 500 m multi-mode fibers is achieved with BERs of <3.3x10(-9) in intensity
      modulation and direct-detection systems employing directly modulated DFB lasers.
      Excellent performance robustness is also observed to various offset launch
      conditions. This work is a significant breakthrough in demonstrating the great
      potential of OOFDM for practical implementation in optical networks.

PMID- 19770882
TI  - Analysis of photonic band structure in a one-dimensional photonic crystal
      containing single-negative materials.
AB  - A theoretical analysis on the angle- and thickness-dependent photonic band
      structure in a one-dimensional photonic crystal containing single-negative (SNG)
      materials is presented. The photonic crystal consists of two alternating SNG
      materials, including that one has a negative permittivity (ENG) and the other has
      a negative permeability (MNG). It is found that there are two types of SNG gaps.
      The first is the low-frequency gap which is very insensitive to the incident
      angle in the transversal electric (TE) wave. The second gap, which strongly
      relies on the incident angle for both TE and transversal magnetic (TM) waves,
      will close at the zero bandgap frequency at which the impedance match as well as
      the phase match in the constituent ENG and MNG layers must be simultaneously
      satisfied. This zero bandgap frequency is also strongly dependent on the incident
      angle. The band edges and the gap maps are investigated rigorously as a function
      of the incident angle and the ratio of thickness of the two SNG layers. The
      analyses are made in the lossless and lossy cases for both TE and TM waves. The
      inclusion of the loss enables us to further clarify two fundamentally distinct
      second SNG gaps which are separated by a threshold angle of incidence.

PMID- 19770883
TI  - Experimental bioluminescence tomography with fully parallel radiative-transfer
      based reconstruction framework.
AB  - Bioluminescence imaging is a very sensitive imaging modality, used in preclinical
      molecular imaging. However, in its planar projection form, it is non-quantitative
      and has poor spatial resolution. In contrast, bioluminescence tomography (BLT)
      promises to provide three dimensional quantitative source information. Currently,
      nearly all BLT reconstruction algorithms in use employ the diffusion
      approximation theory to determine light propagation in tissues. In this process,
      several approximations and assumptions that are made severely affect the
      reconstruction quality of BLT. It is therefore necessary to develop novel
      reconstruction methods using high-order approximation models to the radiative
      transfer equation (RTE) as well as more complex geometries for the whole-body of
      small animals. However, these methodologies introduce significant challenges not
      only in terms of reconstruction speed but also for the overall reconstruction
      strategy. In this paper, a novel fully-parallel reconstruction framework is
      proposed which uses a simplified spherical harmonics approximation (SPN). Using
      this framework, a simple linear relationship between the unknown source
      distribution and the surface measured photon density can be established. The
      distributed storage and parallel operations of the finite element-based matrix
      make SPN-based spectrally resolved reconstruction feasible at the small animal
      whole body level. Performance optimization of the major steps of the framework
      remarkably improves reconstruction speed. Experimental reconstructions with mouse
      shaped phantoms and real mice show the effectiveness and potential of this
      framework. This work constitutes an important advance towards developing more
      precise BLT reconstruction algorithms that utilize high-order approximations,
      particularly second-order self-adjoint forms to the RTE for in vivo small animal
      experiments.

PMID- 19770884
TI  - Interferometric adaptive optics testbed for laser pointing, wave-front control
      and phasing.
AB  - Implementing the capability to perform fast ignition experiments, as well as,
      radiography experiments on the National Ignition Facility (NIF) places stringent
      requirements on the control of each of the beam's pointing, intra-beam phasing
      and overall wave-front quality. In this article experimental results are
      presented which were taken on an interferometric adaptive optics testbed that was
      designed and built to test the capabilities of such a system to control phasing,
      pointing and higher order beam aberrations. These measurements included
      quantification of the reduction in Strehl ratio incurred when using the MEMS
      device to correct for pointing errors in the system. The interferometric adaptive
      optics system achieved a Strehl ratio of 0.83 when correcting for a piston,
      tip/tilt error between two adjacent rectangular apertures, the geometry expected
      for the National ignition Facility. The interferometric adaptive optics system
      also achieved a Strehl ratio of 0.66 when used to correct for a phase plate
      aberration of similar magnitude as expected from simulations of the ARC beam
      line. All of these corrections included measuring both the upstream and
      downstream aberrations in the testbed and applying the sum of these two
      measurements in open-loop to the MEMS deformable mirror.

PMID- 19770885
TI  - Complex 2D photonic crystals with analogue local symmetry as 12-fold
      quasicrystals.
AB  - We construct fourteen complex periodic two-dimensional (2D) photonic structures
      with different structural symmetries by arranging the small portions of a 12-fold
      quasicrystal on square or hexagonal lattices. The corresponding reciprocal
      lattices confirm that all of them demonstrate the 12-fold-like characteristics
      due to the analogue short-range arrangements. We then investigate their photonic
      bandgap properties at different dielectric contrast levels (dielectric rods in
      air background). Our results suggest that all structures possess analogue
      transverse magnetic (TM) gaps in both Si and glass photonic crystals due to the
      similarity of their local geometries. However, the arrangements of the basic
      elements, total symmetries, and the coupling between the local and the lattice
      symmetries have greater impact on the glass photonic crystals, which show much
      larger deviation of gap sizes from different structures. Furthermore, we find
      that the minimal dielectric contrast to achieve the TM gap in the complex
      lattices (dielectric-in-air) can be as low as epsilon = 1.44, whereas the inverse
      structures may open a 2D complete gap in silicon nitride (epsilon = 4.1).

PMID- 19770886
TI  - Solid-core tellurite glass fiber for infrared and nonlinear applications.
AB  - By optimizing glass composition and using a multistage dehydration process, a
      ternary 80TeO(2)-10ZnO-10Na(2)O glass is obtained that shows excellent
      transparency in the wavelength range from 0.38 microm up to 6.10 microm. Based on
      this optimized composition, we report on the fabrication of a single-mode solid
      core tellurite glass fiber with large mode area of 103 microm(2) and low loss of
      0.24-0.7 dB/m at 1550 nm. By using the continuous-wave self-phase modulation
      method, the non-resonant nonlinear refractive index n(2) and the effective
      nonlinear parameter gamma of this made tellurite glass fiber were estimated to be
      3.8x10(-19) m(2)/W and 10.6 W(-1) x km(-1) at 1550 nm, respectively.

PMID- 19770887
TI  - Quantum correlated light beams from non-degenerate four-wave mixing in an atomic
      vapor: the D1 and D2 lines of 85Rb and 87Rb.
AB  - We present experimental results showing that quantum correlated light can be
      produced using non-degenerate, off-resonant, four-wave mixing (4WM) on both the
      D1 (795 nm) and D2 (780 nm) lines of (85)Rb and (87)Rb, extending earlier work on
      the D1 line of (85)Rb. Using this 4WM process in a hot vapor cell to produce
      bright twin beams, we characterize the degree of intensity-difference noise
      reduction below the standard quantum limit for each of the four systems. Although
      each system approximates a double-lambda configuration, differences in details of
      the actual level structure lead to varying degrees of noise reduction. The
      observation of quantum correlations on light produced using all four of these
      systems, regardless of their substructure, suggests that it should be possible to
      use other systems with similar level structures in order to produce narrow
      frequency, non-classical beams at a particular wavelength.

PMID- 19770888
TI  - Particle size limits when using optical trapping and deflection of particles for
      sorting using diode laser bars.
AB  - We explore a simple, inexpensive approach to large particle manipulation using
      diode laser bar optical trapping. This method overcomes limitations that prevent
      conventional point laser traps from effectively directing large particles.
      Expanding a previously developed line optical trap model into larger particle
      regimes, we verify and examine the advantages and limitations of diode laser bar
      trapping for manipulating particles greater than 100 microm in diameter within
      fluidic environments for biochemical, biological, and biomedical applications.

PMID- 19770889
TI  - An electric-field-active 1377-nm narrow-line Si light-emitting diode at 150 K.
AB  - A new class of silicon-based light-emitting diode is demonstrated using InSb
      quantum-dot-embedded Si containing the emissive {311} rod-like defects (RLDs). A
      narrow peak centered at 1377 nm (900 meV) characteristic of the {311} RLDs was
      found to develop out of an otherwise broad background electroluminescence (EL)
      upon the application of electric fields in the growth direction. Such electric
      field-active EL was observed up to 150 K with a slight downward shift of the peak
      energies, accompanied by an anomaly in the thermal roll-off of the EL intensity.
      Spectral variations with temperature and electric field indicate a switching of
      dominance between the closely correlated defect states that are responsible for
      the EL emission.

PMID- 19770890
TI  - Mixed plasmons coupling for expanding the bandwidth of near-perfect absorption at
      visible frequencies.
AB  - We theoretically investigate the electromagnetic response of mixed-size sub
      wavelength square hole array (M-SHA) combined with thick metal layer (TML). Near
      perfect absorption with bandwidth about 17 nm is firstly observed. Field
      distribution and dispersion relationship indicate that mixed surface plasmons (M
      SPs) coupling is supported by M-SHA and TML. The absorption band is proved to be
      dominated by M-SPs coupling.

PMID- 19770891
TI  - All-fiber bandwidth-tunable band-rejection filter based on a composite grating
      induced by CO2 laser pulses.
AB  - We propose an all-fiber band-rejection filter with a tunable bandwidth, which is
      realized by putting a normal long-period fiber grating in series with a rotary
      long-period fiber grating written in a twisted single-mode fiber by CO(2) laser
      pulses. Bandwidth tuning is achieved by applying torsion to the composite
      grating. Our experimental filter shows a bandwidth tuning of approximately 16.3
      nm at a rejection level of approximately 15 dB and a polarization-dependent loss
      lower than approximately 0.9 dB.

PMID- 19770892
TI  - A theoretical model for sampled grating DBR laser integrated with SOA and MZ
      modulator.
AB  - A theoretical model is presented for simulating the sampled grating distributed
      Bragg reflector (SGDBR) laser integrated with semiconductor optical amplifier
      (SOA) and Mach-Zehnder (MZ) modulator. In this model, the active and passive
      sections are processed separately. The active region of laser and the SOA section
      are modeled by time domain traveling wave (TDTW) method. While the spectral
      properties of the SG and the MZ modulator are firstly calculated by Transfer
      Matrix Method (TMM) and Beam Propagation Method (BPM), respectively, and then
      transformed into time domain using digital filter approach. Furthermore, the
      nonuniform carrier-dependence of gain and refractive index are also incorporated
      via Effective Bloch Equations (EBE). Compared with the full time-domain method,
      our model would be more flexible and efficient. The static and modulation
      performances of device are successfully simulated. This indicates that it can be
      a powerful platform for investigating the complex Photonic Integrated Circuits
      (PICs).

PMID- 19770893
TI  - Reduction of the amplified spontaneous emission threshold in semiconducting
      polymer waveguides on porous silica.
AB  - Hybrid organic-inorganic monomode waveguides of conjugated polymers on porous
      silicon (PS) substrates have been fabricated. Different low refractive index PS
      substrates, varying from 1.46 down to 1.18 have been studied. Amplified
      spontaneous emission (ASE) has been observed for all the samples and the ASE
      threshold has been monitored as a function of the PS refractive index. A decrease
      in the ASE threshold is detected when the PS refractive index decreases. These
      results have been analysed in the frame of a four level waveguide amplifier model
      and the theoretical predictions are in agreement with the experimental data.

PMID- 19770894
TI  - Atomic magnetometry with maximally polarized states.
AB  - A new magnetometry method based on electromagnetic induced transparency (EIT)
      with maximally polarized states is demonstrated. An EIT hyperfine resonance,
      comprising the m(F)=F state (end-state), is observed at a non-zero angle between
      the laser beam and the magnetic field. The method takes advantage of the process
      of end-state pumping, a well-known rival of simpler EIT magnetometry schemes, and
      therefore benefits at a high laser power. An experimental demonstration and a
      numerical analysis of the magnetometry method are presented. The analysis points
      on a clear sensitivity advantage of the end-state EIT magnetometer.

PMID- 19770895
TI  - Plasmonic interference nanolithography with a double-layer planar silver lens
      structure.
AB  - We present here a surface plasmon interference lithography method with double
      layer planar silver lens. This kind of lithography method provides interference
      patterns with sufficient contrast for lithography process and simple structure
      for the convenience of fabrication. Rigorous coupled wave analysis method has
      been performed with practical parameters to testify this lithography scheme.
      Furthermore, some key factors influencing the pattern quality have been
      discussed. It is pointed out that three factors mainly determine the resolution
      of the interference patterns, and therefore we give a theoretical resolution
      limit of about 1/12 wavelength to the surface plasmon interference lithography
      method.

PMID- 19770896
TI  - Modeling of enhanced field confinement and scattering by optical wire antennas.
AB  - We describe the application of full-wave and semi-analytical numerical tools for
      the modeling of optical wire antennas, with the aim of providing novel guidelines
      for analysis and design. The concept of antenna impedance at optical frequencies
      is reviewed by means of finite-element simulations, whereas a surface-impedance
      integral equation is derived in order to perform an accurate and efficient
      calculation of the current distribution, and thereby to determine the equivalent
      circuit parameters. These are introduced into simple circuits models, directly
      borrowed from radio frequency, which are applied in order to model the phenomena
      of enhanced field confinement at the feed gap and light scattering by optical
      antennas illuminated by plane waves.

PMID- 19770897
TI  - Nonlinear optical frequency conversion of an amplified Fourier Domain Mode Locked
      (FDML) laser.
AB  - We report on the highly efficient non-linear optical frequency conversion of the
      wavelength swept output from a Fourier Domain Mode Locked (FDML) laser. Different
      concepts for power scaling of FDML lasers by post-amplification with active
      fibers are presented. A two-stage post-amplification of an FDML laser with an
      amplification factor of 300 up to a peak power of 1.5 W is used to supply
      sufficient power levels for non-linear conversion. Using a single-mode dispersion
      shifted fiber (DSF), we convert this amplified output that covers the region
      between 1541 nm and 1545 nm to a wavelength range from 1572 nm to 1663 nm via
      modulation instability (MI). For this four wave mixing process we observe an
      efficiency of approximately 40%. The anti-Stokes signal between 1435 nm and 1516
      nm was observed with lower conversion efficiency. In addition to shifting the
      wavelength, the effect of MI also enables a substantial increase in the
      wavelength sweep rate of the FDML laser by a factor of approximately 50 to 0.55
      nm/ns.

PMID- 19770898
TI  - Optimization of an off-axis three-mirror anastigmatic system with wavefront
      coding technology based on MTF invariance.
AB  - In this paper the invariance of modulation transfer function (MTF), which
      describes the insensitivity to perturbation of MTF, is defined to be the
      evaluating criterion of the wavefront coding system. The rapid optimization of
      wavefront coding system based on the MTF invariance is proposed by means of
      introducing the mathematical program Matlab to normal optical design process. The
      interface called MZDDE between Matlab and Zemax is applied to realize the fast
      data exchanging and merit function calculating. The genetic algorithm tool (GA)
      in Matlab is introduced to the optimizing process, which accelerates the
      converging efficiency considerably. The MTF invariance of optimized system drops
      to 0.0119 while that of original system is larger than 0.018. If the all the
      fields of view is taken into consideration, the MTF invariance of optimized
      system and original system is less than 0.015 and larger than 0.020 respectively.
      It is proven that the optimization of the unusual optical system with special
      property can be executed conveniently and rapidly with the help of external
      program and dynamic data exchange.

PMID- 19770899
TI  - Sinusoidal B-M method based spectral domain optical coherence tomography for the
      elimination of complex-conjugate artifact.
AB  - A high speed spectral domain optical coherence tomography based on the spatial
      sinusoidal phase modulation for the elimination of complex-conjugate artifact is
      presented, where sinusoidal phase modulation of reference arm (M scan) and
      transverse scanning of sample arm (B scan) are performed simultaneously
      (sinusoidal B-M method). Herein, the linear phase modulation of the reference arm
      in conventional linear B-M method is modified to sinusoidal phase modulation. The
      proposed sinusoidal B-M method relaxes the requirements on the phase-shifting
      mechanical system and avoids sensitivity fall-off along the transverse direction
      in contrast to the linear B-M method. A criterion for the relation between
      transverse over-sampling factor and modulation frequency for optimal complex
      conjugate rejection is deduced and verified by experiments. Under this criterion,
      the complex spectral interferogram is reconstructed by harmonic analysis and
      digital synchronous demodulation. Double imaging depth range on fresh shrimp at A
      scan rate of 10 kHz with complex conjugate rejection ratio up to 45 dB is
      achieved.

PMID- 19770901
TI  - Implementation and characterization of a stable optical frequency distribution
      system.
AB  - An optical frequency distribution system has been developed that continuously
      delivers a stable optical frequency of 268 THz (corresponding to a wavelength of
      1118 nm) to different experiments in our institute. For that purpose, a
      continuous wave (cw) fiber laser has been stabilized onto a frequency comb and
      distributed across the building by the use of a fiber network. While the light
      propagates through the fiber, acoustic and thermal effects counteract against the
      stability and accuracy of the system. However, by employing proper stabilization
      methods a stability of 2 x 10(-13) tau(-1/2) is achieved, limited by the
      available radio frequency (RF) reference. Furthermore, the issue of counter
      dependant results of the Allan deviation was examined during the data evaluation.

PMID- 19770900
TI  - Three-dimensional bioluminescence tomography based on Bayesian approach.
AB  - Bioluminescence tomography (BLT) poses a typical ill-posed inverse problem with a
      large number of unknowns and a relatively limited number of boundary
      measurements. It is indispensable to incorporate a priori information into the
      inverse problem formulation in order to obtain viable solutions. In the paper,
      Bayesian approach has been firstly suggested to incorporate multiple types of a
      priori information for BLT reconstruction. Meanwhile, a generalized adaptive
      Gaussian Markov random field (GAGMRF) prior model for unknown source density
      estimation is developed to further reduce the ill-posedness of BLT on the basis
      of finite element analysis. Then the distribution of bioluminescent source can be
      acquired by maximizing the log posterior probability with respect to a noise
      parameter and the unknown source density. Furthermore, the use of finite element
      method makes the algorithm appropriate for complex heterogeneous phantom. The
      algorithm was validated by numerical simulation of a 3-D micro-CT mouse atlas and
      physical phantom experiment. The reconstructed results suggest that we are able
      to achieve high computational efficiency and accurate localization of
      bioluminescent source.

PMID- 19770902
TI  - Phase-shifts n pi/2 calibration method for phase-stepping interferometry.
AB  - A novel phase-shifts n pi/2 calibration method for phase-stepping interferometry,
      in which the sum intensities and the squared sum of a series of phase-shifted
      interferograms are firstly calculated, and then by the minimization of the
      variances of these sums perform the n pi/2 phase-shifts calibration, is proposed
      in this paper. The proposed method can overcome effectively the effect of the
      variations of background and modulation intensities in interferograms with any
      phase structure, and it is also insensitive to the nonlinearity of phase shifter.
      Numerical simulation and experiments are implemented to verify the effectiveness
      of this method.

PMID- 19770903
TI  - Non-ideal cloaking based on Fabry-Perot resonances in single-layer high-index.
AB  - Strong reduction of the scattering cross section is obtained for subwavelength
      dielectric and conducting cylinders without any magnetism for both TE and TM
      polarizations. The suggested approach is based on the use of Fabry-Perot type
      radial resonances, which can appear in single-layer, high-epsilon, isotropic, and
      homogeneous shells with the properly chosen parameters. Frequencies of the minima
      of the scattering cross section, which are associated with the cloaking,
      typically depend on whether TE or TM polarization is considered. In some cases,
      large-positive-epsilon and large-negative-epsilon objects can be cloaked. In
      other cases, non-ideal multifrequency cloaking can be realized.

PMID- 19770904
TI  - Excitation of two-colored temporal solitons in a segmented quasi-phase-matching
      structure.
AB  - We conducted a numerical study on the excitation of a two-colored temporal
      soliton in a segmented quasi-phase-matching (QPM) structure. The device has three
      parts: a periodic QPM grating for second-harmonic generation, a single domain for
      phase shift, and a periodic QPM grating for soliton evolution. The second
      harmonic pulse generated in the first grating works as a seed in the cascaded up
      and-down conversions in the second grating. The numerical results showed that the
      second harmonic seeding enables the excitation of soliton pulses with an improved
      spatio-temporal intensity profile in a broad bandwidth of the wave-vector
      mismatch.

PMID- 19770905
TI  - Multipixel silicon avalanche photodiode with ultralow dark count rate at liquid
      nitrogen temperature.
AB  - Multipixel silicon avalanche photodiodes (Si APDs) are novel photodetectors used
      as silicon photomultipliers (SiPMs), or multipixel photon counter (MPPC), because
      they have fast response, photon-number resolution, and a high count rate; one
      drawback, however, is the high dark count rate. We developed a system for cooling
      an MPPC to liquid nitrogen temperature and thus reduce the dark count rate. Our
      system achieved dark count rates of <0.2 cps. Here we present the afterpulse
      probability, counting capability, timing jitter, and photon-number resolution of
      our system at 78.5 K and 295 K.

PMID- 19770906
TI  - 4 Gbps impulse radio (IR) ultra-wideband (UWB) transmission over 100 meters multi
      mode fiber with 4 meters wireless transmission.
AB  - We present experimental demonstrations of in-building impulse radio (IR) ultra
      wideband (UWB) link consisting of 100 m multi mode fiber (MMF) and 4 m wireless
      transmission at a record 4 Gbps, and a record 8 m wireless transmission at 2.5
      Gbps. A directly modulated vertical cavity surface emitting laser (VCSEL) was
      used for the generation of the optical signal. 8 m at 2.5 Gbps corresponds to a
      bit rate--distance product of 20; the highest yet reported for wireless IR-UWB
      transmission.

PMID- 19770907
TI  - OSNR variation of multiple laser lines in Brillouin-Raman fiber laser.
AB  - We report experimental results demonstrating the variation of optical signal-to
      noise ratio (OSNR) of laser lines in Brillouin-Raman fiber laser against Raman
      pump power (RPP) variation. The reduction of OSNR is attributed to the spectral
      broadening of laser lines depending on the RPP. The spectral broadening is owing
      to the effect of the interaction between laser lines and turbulent waves
      (nonlinear interaction between longitudinal cavity modes). In our experiment, the
      worst OSNR is obtained at 650 mW RPP as a result of maximum spectral broadening
      when the Brillouin pump wavelength is fixed at 1555 nm. On the other hand, the
      OSNR improvement is obtained for RPP beyond 650 mW due to the effect of red
      shift, the Raman peak gain is shifted away from the laser lines generated around
      1555 nm thus reduces the spectral broadening effect.

PMID- 19770908
TI  - 130-W picosecond green laser based on a frequency-doubled hybrid cryogenic Yb:YAG
      amplifier.
AB  - 130-W average-power picosecond green laser pulses at 514.5 nm are generated from
      a frequency-doubled hybrid cryogenic Yb:YAG laser. A second-harmonic conversion
      efficiency of 54% is achieved with a 15-mm-long noncritically phase-matched
      lithium triborate (LBO) crystal from a 240-W 8-ps 78-MHz pulse train at 1029 nm.
      The high-average-power hybrid laser system consists of a picosecond fiber chirped
      pulse amplification seed source and a cryogenically-cooled double-pass Yb:YAG
      amplifier. The M(2) value of 2.7, measured at 77 W of second-harmonic power,
      demonstrates a good focusing quality. A thermal analysis shows that the
      longitudinal temperature gradient can be the main limiting factor in the second
      harmonic efficiency. To our best knowledge, this is the highest-average-power
      green laser source generating picosecond pulses.

PMID- 19770909
TI  - Jump method for optical thin film design.
AB  - This paper proposes a method called Jump method for optimization of optical thin
      films. The method is the combination of local search strategy using modified
      Coordinate-Wise Algorithm and global search strategy using modified Evolutionary
      Algorithm. Jump method can evolve the designs of optical thin films for good
      performances. The design of a dielectric beam splitter and an edge filter as
      examples is carried out and the results indicate that Jump method is a very
      robust algorithm for optical thin film designs.

PMID- 19770911
TI  - Single-mode delivery of 250 nm light using a large mode area photonic crystal
      fiber.
AB  - We demonstrate that large mode area (LMA) photonic crystal fibers (PCFs) can be
      used as single-mode patch-cords for 250 nm laser light. We have studied the
      transmission of the 250 nm output beam of a frequency-quadrupled diode laser
      through a triangular structure LMA PCF with 10 microm core. We have achieved
      single-mode output with coupling loss of 1.8 +/- 0.6 dB and transmission loss of
      1.5 +/- 0.2 dB/m. The critical bend loss radius is approximately 6 cm. The
      transmission loss is compared with published bulk silica measurements. Effects of
      optically induced damage were observed after prolonged operation and have been
      studied as function of laser power and time. The optical damage occurs primarily
      at the fiber input and can be partly ameliorated by cleaving the fiber input. For
      input power levels of < approximately 0.3 mW stable operation can be achieved for
      periods of >40 hours which is sufficient for many laboratory based applications.
      The results show the utility of these fibers for single-mode beam delivery in a
      spectral region where step-index single-mode fibers are not readily available.

PMID- 19770910
TI  - Beam control and multi-color routing with spatial photonic defect modes.
AB  - We demonstrate tunable re-directing, blocking, and splitting of a light beam
      along defect channels based on spatial bandgap guidance in two-dimensional
      photonic lattices. We show the possibility for linear control of beam propagation
      and multicolor routing with specially designed junctions and surface structures
      embedded in otherwise uniform square lattices.

PMID- 19770912
TI  - Highly stable and efficient erbium-doped 2.8 microm all fiber laser.
AB  - We demonstrate the efficient and stable CW laser operation at 2.824 microm of a
      diode-pumped erbium-doped fluoride fiber laser employing an intracore fiber Bragg
      grating high reflector. An output power of 5 W and an optical-to-optical
      conversion efficiency of 32% are reported. The temporal and spectral stability of
      the laser represent a significant improvement over previous work. This report
      paves the way to the commercialization of compact and stable fiber lasers for
      spectroscopic and medical applications.

PMID- 19770913
TI  - Proposal of a grating-based optical reflection switch using phase change
      materials.
AB  - We have proposed a novel grating-based optical reflection switch using a phase
      change material (PCM). The device switches on/off light or shifts the light
      propagation direction by switching the PCM grating between its amorphous and
      crystalline states. Thus, the switching status is non-volatile and the device is
      promising for realizing low power consumption. The device structure was designed
      and optimized by numerical simulations to obtain high switching efficiency. It is
      shown that there exists a parameter window where high efficiency is achievable.
      The static switching characteristics were confirmed by finite-difference time
      domain (FDTD) simulations. The design scheme can also be applied to other planar
      dielectric gratings.

PMID- 19770914
TI  - Performance of reduced bit-depth acquisition for optical frequency domain
      imaging.
AB  - High-speed optical frequency domain imaging (OFDI) has enabled practical wide
      field microscopic imaging in the biological laboratory and clinical medicine. The
      imaging speed of OFDI, and therefore the field of view, of current systems is
      limited by the rate at which data can be digitized and archived rather than the
      system sensitivity or laser performance. One solution to this bottleneck is to
      natively digitize OFDI signals at reduced bit depths, e.g., at 8-bit depth rather
      than the conventional 12-14 bit depth, thereby reducing overall bandwidth.
      However, the implications of reduced bit-depth acquisition on image quality have
      not been studied. In this paper, we use simulations and empirical studies to
      evaluate the effects of reduced depth acquisition on OFDI image quality. We show
      that image acquisition at 8-bit depth allows high system sensitivity with only a
      minimal drop in the signal-to-noise ratio compared to higher bit-depth systems.
      Images of a human coronary artery acquired in vivo at 8-bit depth are presented
      and compared with images at higher bit-depth acquisition.

PMID- 19770915
TI  - Detection and characterization of carbon contamination on EUV multilayer mirrors.
AB  - In this paper, we detect and characterize the carbon contamination layers that
      are formed during the illumination of extreme ultraviolet (EUV) multilayer
      mirrors. The EUV induced carbon layers were characterized ex situ using
      spectroscopic ellipsometry (SE) and laser generated surface acoustic waves (LG
      SAW). We show that both LG-SAW and SE are very sensitive for measuring carbon
      layers, even in the presence of the highly heterogeneous structure of the
      multilayer. SE has better overall sensitivity, with a detection limit of 0.2 nm,
      while LG-SAW has an estimated detection limit of 2 nm. In addition, SE reveals
      that the optical properties of the EUV induced carbon contamination layer are
      consistent with the presence of a hydrogenated, polymeric like carbon. On the
      other hand, LG-SAW reveals that the EUV induced carbon contamination layer has a
      low Young's modulus (<100 GPa), which means that the layer is mechanically soft.
      We compare the limits of detection and quantification of the two techniques and
      discuss their prospective for monitoring carbon contamination build up on EUV
      optics.

PMID- 19770916
TI  - Multi-pulse oscillation and instabilities in microchip self-Q-switched transverse
      mode laser.
AB  - Multi-transverse-mode competition, coupling induced instabilities and multi-pulse
      or satellite pulse oscillations were investigated experimentally and
      theoretically in laser-diode-pumped Cr,Nd:YAG self-Q-switched microchip lasers
      under large pump beam diameter. The different transverse modes have great effects
      on the laser pulse temporal characteristics such as pulse profile, pulse width,
      instability of peak power and repetition rate jitter. Multi-transverse-mode,
      multi-pulse oscillation and periodical pulsation were observed by varying the
      pump beam diameter.The effect of transverse modes on the instability and multi
      pulse oscillation were studied by modified coupled rate equations by taking into
      account the transverse-mode competition of inversion population under different
      pump conditions. The numerically simulated results are in good agreement with the
      experimental results. These results show that the multi-pulse oscillation and
      instability in the pulse train were attributed to different transverse mode
      coupling and competition. The peak power instabilities and pulse repetition rate
      jitter of the laser pulses due to transverse mode coupling were also
      investigated.

PMID- 19770917
TI  - Electromechanical film as a photoacoustic transducer.
AB  - An electromechanical film, EMFi, is utilized as a transducer in a photoacoustic
      (PA) gas sensor. The film is a sensitive acoustic transducer, it is easily
      formable, and it exhibits a wide frequency response regardless of its large
      surface area. As a demonstration of its capabilities, the EMFi-based PA detector
      is used to measure NO(2) with pulsed excitation at 436 and 473 nm. The minimum
      detectable absorption coefficient is extrapolated to be 5.10(-7) cm(-1).
      Improvements for EMFi-based PA detector are discussed.

PMID- 19770918
TI  - Bound and free waves in non-collinear second harmonic generation.
AB  - We analyze the relationship between the bound and the free waves in the
      noncollinear SHG scheme, along with the vectorial conservation law for the
      different components arising when there are two pump beams impinging on the
      sample with two different incidence angles. The generated power is systematically
      investigated, by varying the polarization state of both fundamental beams, while
      absorption is included via the Herman and Hayden correction terms. The
      theoretical simulations, obtained for samples which are some coherence length
      thick show that the resulting polarization mapping is an useful tool to put in
      evidence the interference between bound and free waves, as well as the effect of
      absorption on the interference pattern.

PMID- 19770919
TI  - Observation of extreme temporal events in CW-pumped supercontinuum.
AB  - We study experimentally and numerically the temporal features of supercontinuum
      generated with a continuous-wave ytterbium-doped fiber laser. We show that the
      temporal output of the supercontinuum is characterized by strong and brief power
      fluctuations, i.e. so-called optical rogue waves. We demonstrate numerically that
      these rare and strong events that appear and disappear from nowhere result from
      solitonic collisions.

PMID- 19770921
TI  - Real-time monitoring of continuous-wave terahertz radiation using a fiber-based,
      terahertz-comb-referenced spectrum analyzer.
AB  - We propose a fiber-based, terahertz-comb-referenced spectrum analyzer which has
      the advantages of being a portable, alignment-free, robust, and flexible
      apparatus suitable for practical use. To this end, we constructed a 1550-nm mode
      locked Er-doped fiber laser whose mode-locked frequency was stabilized precisely
      by referring to a rubidium frequency standard, and used it to generate a highly
      stable terahertz (THz) frequency comb in a photoconductive antenna or an electro
      optic crystal. By standardizing the THz comb, we determined the frequency
      accuracy of an active-frequency-multiplier-chain (AFMC) source to be 2.4 x 10(
      11). Furthermore, the potential of the THz spectrum analyzer was effectively
      demonstrated by real-time monitoring of the spectral behavior of the AFMC source
      and a photomixing source of two free-running CW lasers at adjacent wavelengths.

PMID- 19770920
TI  - Late-fluorescence mammography assesses tumor capillary permeability and
      differentiates malignant from benign lesions.
AB  - Using scanning time-domain instrumentation we recorded fluorescence projection
      mammograms on few breast cancer patients prior, during and after infusion of
      indocyanine green (ICG), while monitoring arterial ICG concentration by
      transcutaneous pulse densitometry. Late-fluorescence mammograms recorded after
      ICG had been largely cleared from the blood by the liver, showed invasive
      carcinomas at high contrast over a rather homogeneous background, whereas benign
      lesions did not produce (focused) fluorescence contrast. During infusion, tissue
      concentration contrast and hence fluorescence contrast is determined by
      intravascular contributions, whereas late-fluorescence mammograms are dominated
      by contributions from protein-bound ICG extravasated into the interstitium,
      reflecting relative microvascular permeabilities of carcinomas and normal breast
      tissue. We simulated intravascular and extravascular contributions to ICG tissue
      concentration contrast within a two-compartment unidirectional pharmacokinetic
      model.

PMID- 19770922
TI  - Raman microscopy based on doubly-resonant four-wave mixing (DR-FWM).
AB  - Doubly-resonant four-wave mixing (DR-FWM) is a nondegenerate four-wave mixing
      process in which four photons interact to coherently probe two distinct Raman
      resonances. We demonstrate DR-FWM microscopy as a label-free and nondestructive
      molecular imaging modality with high chemical specificity on the submicron scale
      by imaging alkyne-substituted oleic acid in both aqueous and lipid-rich
      environments. DR-FWM microscopy is contrasted to coherent anti-Stokes Raman
      scattering (CARS) microscopy and it is shown that the coherent addition of two
      simultaneously probed Raman resonances leads to a significant increase in signal
      without increasing the non-resonant background. Thus, this scheme enables the
      detection of weak Raman signals through amplification by a strong Raman
      resonance, potentially increasing the overall detection sensitivity beyond what
      has been demonstrated by either CARS or stimulated Raman scattering (SRS).

PMID- 19770923
TI  - Phase noise estimation and mitigation for DCT-based coherent optical OFDM
      systems.
AB  - In this paper, as an attractive alternative to the conventional discrete Fourier
      transform (DFT) based orthogonal frequency division multiplexing (OFDM), discrete
      cosine transform (DCT) based OFDM which has certain advantages over its
      counterpart is studied for optical fiber communications. As is known, laser phase
      noise is a major impairment to the performance of coherent optical OFDM (CO-OFDM)
      systems. However, to our knowledge, detailed analysis of phase noise and the
      corresponding mitigation methods for DCT-based CO-OFDM systems have not been
      reported yet. To address these issues, we analyze the laser phase noise in the
      DCT-based CO-OFDM systems, and propose phase noise estimation and mitigation
      schemes. Numerical results show that the proposal is very effective in
      suppressing phase noise and could significantly improve the performance of DCT
      based CO-OFDM systems.

PMID- 19770924
TI  - Planar photonic crystal microspectrometers in silicon-nitride for the visible
      range.
AB  - We demonstrate the feasibility of forming a compact integrated photonic
      spectrometer for operation in the visible wavelength range using the dispersive
      properties of a planar photonic crystal structure fabricated in silicon nitride.
      High wavelength resolution and compact device sizes in these spectrometers are
      enabled by combining superprism effect, negative diffraction effect, and negative
      refraction effect in a 45 degree rotated square lattice photonic crystal. Our
      experimental demonstration shows 1.2 nm wavelength resolution in a 70 microm by
      130 microm photonic crystal structure with better performance than alternative
      structures for on-chip spectroscopy, confirming the unique capability of the
      proposed approach to realize compact integrated spectrometers.

PMID- 19770925
TI  - Evolution of the frequency chirp of Gaussian pulses and beams when passing
      through a pulse compressor.
AB  - The evolution of the frequency chirp of a laser pulse inside a classical pulse
      compressor is very different for plane waves and Gaussian beams, although after
      propagating through the last (4th) dispersive element, the two models give the
      same results. In this paper, we have analyzed the evolution of the frequency
      chirp of Gaussian pulses and beams using a method which directly obtains the
      spectral phase acquired by the compressor. We found the spatiotemporal couplings
      in the phase to be the fundamental reason for the difference in the frequency
      chirp acquired by a Gaussian beam and a plane wave. When the Gaussian beam
      propagates, an additional frequency chirp will be introduced if any
      spatiotemporal couplings (i.e. angular dispersion, spatial chirp or pulse front
      tilt) are present. However, if there are no couplings present, the chirp of the
      Gaussian beam is the same as that of a plane wave. When the Gaussian beam is well
      collimated, the introduced frequency chirp predicted by the plane wave and
      Gaussian beam models are in closer agreement. This work improves our
      understanding of pulse compressors and should be helpful for optimizing
      dispersion compensation schemes in many applications of femtosecond laser pulses.

PMID- 19770926
TI  - A miniaturized fiber-coupled terahertz endoscope system.
AB  - In this study, we have designed, fabricated, and characterized a miniaturized
      optical fiber-coupled terahertz (THz) endoscope system. The endoscopic system
      utilized a photoconductive generator and detector driven by a mode-locked
      Ti:sapphire laser. In reflection mode, the endoscope showed a high signal-to
      noise ratio and a wide frequency spectrum similar to the conventional THz time
      domain spectroscopic system. The cross section of the endoscope including
      generator and detector head is (2 x 4 mm) x 6 mm, which is small enough to be
      inserted into a human body. For a feasibility test, the endoscopic system was
      used to measure reflective THz signals from the side wall of the mouth, tongue,
      and palm skin as well as from water for comparison. The absorption and refractive
      index of the side wall of the mouth and tongue were similar to those of water but
      those of the palm skin were less than water.

PMID- 19770927
TI  - THz surface wave collapse on coated metal surfaces.
AB  - The Zenneck THz surface wave (Z-TSW) on metals is discussed with respect to its
      difficulty in generation and measurement. The spatial collapse of the extent of
      the Z-TSW evanescent field, upon the addition of a sub-wavelength dielectric
      layer on the metal surface, is explained by a simple model, in good agreement
      with exact analytical theory. Experimental measurements of the THz surface wave
      on an aluminum surface covered with a 12.5 microm thick dielectric layer have
      completely characterized the resultant single-mode dielectric layer THz surface
      wave (DL-TSW). The measured frequency-dependent exponential fall-off of the
      evanescent wave from the surface agrees well with theory. The DL-TSW frequency
      dependent absorption coefficient, phase velocity, group velocity and group
      velocity dispersion have been obtained. These guided-wave parameters compare
      favorably with other guided wave structures.

PMID- 19770928
TI  - Numerical demonstration of the validity of the Rayleigh hypothesis.
AB  - The Rayleigh hypothesis and the related method of diffraction analysis are
      revisited. It is shown that the Rayleigh method can be applied to deep grating
      modeling without numerical problems and that it gives any desired accuracy
      whatever the groove depth. This proves the validity of the Rayleigh hypothesis
      and rehabilitates the Rayleigh method.

PMID- 19770929
TI  - Thermo-optical dynamics in an optically pumped Photonic Crystal nano-cavity.
AB  - Linear and non-linear thermo-optical dynamical regimes were investigated in a
      photonic crystal cavity. First, we have measured the thermal relaxation time in
      an InP-based nano-cavity with quantum dots in the presence of optical pumping.
      The experimental method presented here allows one to obtain the dynamics of
      temperature in a nanocavity based on reflectivity measurements of a cw probe beam
      coupled through an adiabatically tapered fiber. Characteristic times of 1.0+/-0.2
      micros and 0.9+/-0.2 micros for the heating and the cooling processes were
      obtained. Finally, thermal dynamics were also investigated in a thermo-optical
      bistable regime. Switch-on/off times of 2 micros and 4 micros respectively were
      measured, which could be explained in terms of a simple non-linear dynamical
      representation.

PMID- 19770930
TI  - Experimental demonstration of spectral broadening in an all-silica Bragg fiber.
AB  - We present the first report on experimental observation of nonlinear spectral
      broadening in an all-solid photonic band gap Bragg fiber of relatively large mode
      area approximately 62 microm(2). The theoretically designed Bragg fiber for this
      specific application was fabricated by the well known MCVD technique. Nonlinear
      spectral broadening was observed by launching high power femtosecond pulses of
      1067 nm pump wavelength. These first results indicate that fabrication of such
      Bragg fibers, once perfected, should potentially serve as an alternative route
      for realization of supercontinuum light.

PMID- 19770931
TI  - Light focusing by the unique dielectric nano-waveguide array.
AB  - The light focusing by using dielectric nano-waveguides array with its length in
      micron is investigated via the finite-difference time domain (FDTD) method.
      Simulated results show that the focal length depends on the length and the total
      width of the arrays and can be altered from tens of micron to wavelength order.
      Both TM and TE mode incident light can be focused by the array. The wavelength
      order focal length is achieved by employing the dielectric nano-waveguide array
      with variant separations. The unique focusing behavior is contributed to the
      radiation mode with longer decay length and the large evanescent field which
      appears in the nano-waveguide array. We believe this simulation results can be a
      promising guidance for the experiments.

PMID- 19770932
TI  - Novel technique for the determination of hydroxyl distributions in fused silica.
AB  - Bound OH- is one major unwanted absorbing impurity causing significant
      attenuation for certain wavelengths of laser radiation when propagating through
      fused silica. A wavelength tunable laser calorimeter (LCA) is used to detect
      dopants and other impurities in optical material. Also, a technique for
      photothermal absorption measurements is combined with the LCA set-up allowing for
      a lateral scan of the sample retaining an absolute calibration. Regarding
      inhomogeneities within the distribution of impurities the combination of both
      techniques provides a highly sensitive method to investigate in the lateral
      distribution of OH- content in fused silica.

PMID- 19770933
TI  - Interaction of self-trapped beams in high index glass.
AB  - We observe attraction, repulsion and energy exchange between two self-trapped
      beams in a heavy-metal-oxide glass exhibiting a Kerr-like response with
      multiphoton absorption. The coherent interaction between spatial solitons is
      controlled by their relative phase and modelled by a nonlinear dissipative
      Schrodinger equation.

PMID- 19770934
TI  - Optimal generation of indistinguishable photons from non-identical artificial
      molecules.
AB  - We show theoretically that nearly indistinguishable photons can be generated with
      non-identical semiconductor-based sources. The use of virtual Raman transitions
      and the optimization of the external driving fields increases the tolerance to
      spectral inhomogeneity to the meV energy range. A trade-off emerges between
      photon indistinguishability and efficiency in the photon-generation process.
      Linear (quadratic) dependence of the coincidence probability within the Hong-Ou
      Mandel setup is found with respect to the dephasing (relaxation) rate in the
      semiconductor sources.

PMID- 19770935
TI  - One-pulse driven plasma Pockels cell with DKDP crystal for repetition-rate
      application.
AB  - Pockels cell (PPC), which can use a thin crystal to perform the uniform electro
      optical effect, is ideal component as average-power optical switch with large
      aperture. In this paper, the key problems in PPC are analyzed for repetition-rate
      application, and thermo-optical effects are simulated by means of numerical
      modeling when average power is loaded on the electro-optical crystal. By
      reformative design and employing a capacity to share the gas discharge voltage,
      the DKDP PPC driven by one pulse is realized. As gas breakdown delay time is
      stable, and discharge plasma is uniformly filled the full aperture, it meets the
      demand of plasma electrode for the repetition-rate PPC with DKDP crystal. The
      switch efficiency of PPC at the whole aperture is better than 99%.

PMID- 19770936
TI  - Spectral mapping of the third-order optical nonlinearity of glass-metal
      nanocomposites.
AB  - By tuning wavelengths of the femtosecond pump and probe pulses we mapped the
      nonlinear absorption of copper-glass nanocomposites within 520-620 nm range. At
      the pump intensity of 3 GW/cm(2), the induced transmission rise was as high as
      20%. The imaginary part of the third-order optical susceptibility of the
      nanocomposites as a function of the probe wavelength reproduced well the spectral
      profile of the surface plasmon resonance in copper. In contrast, the imaginary
      part of the third-order optical susceptibility as a function of the pump
      wavelength did not reproduce the plasmon profile being wider than the latter.

PMID- 19770937
TI  - Advanced imaging with dynamic focus and extended depth using integrated FR4
      platform.
AB  - A two-degrees-of-freedom scanned beam imaging system with large dynamic range and
      dynamic focusing is demonstrated. The laser diode, photo-detector and the optical
      components are integrated on a moving platform that is made of FR4 (Flame
      Retardant 4), a common polymeric substrate used in printed circuit boards. A scan
      angle of 52 degrees is demonstrated at 60 Hz resonant frequency while the laser
      is moved 250 um in the out-of-plane direction to achieve dynamic focusing. The
      laser is scanned by physically rotating the laser diode and the collection optics
      to achieve high signal-to-noise ratio and good ambient light rejection. The
      collection optics is engineered such that the collection efficiency decreases
      when collecting light from close distances to avoid detector saturation. The
      detection range is extended from contact distance up to 600 mm while the
      collected power level varies only by a factor of 30 within this long range.
      Slight modifications will allow increasing the detection range up to one meter.
      This is the first demonstration of a laser scan engine with such a high degree of
      integration of electronics, optoelectronics, optics and micromechanics on the
      same platform.

PMID- 19770938
TI  - Optical tweezers with millikelvin precision of temperature-controlled objectives
      and base-pair resolution.
AB  - In optical tweezers, thermal drift is detrimental for high-resolution
      measurements. In particular, absorption of the trapping laser light by the
      microscope objective that focuses the beam leads to heating of the objective and
      subsequent drift. This entails long equilibration times which may limit sensitive
      biophysical assays. Here, we introduce an objective temperature feedback system
      for minimizing thermal drift. We measured that the infrared laser heated the
      objective by 0.7 K per watt of laser power and that the laser focus moved
      relative to the sample by approximately 1 nm/mK due to thermal expansion of the
      objective. The feedback stabilized the temperature of the trapping objective with
      millikelvin precision. This enhanced the long-term temperature stability and
      significantly reduced the settling time of the instrument to about 100 s after a
      temperature disturbance while preserving single DNA base-pair resolution of
      surface-coupled assays. Minimizing systematic temperature changes of the
      objective and concurrent drift is of interest for other high-resolution
      microscopy techniques. Furthermore, temperature control is often a desirable
      parameter in biophysical experiments.

PMID- 19770939
TI  - Tunable multiwavelength SOA fiber laser with ultra-narrow wavelength spacing
      based on nonlinear polarization rotation.
AB  - A tunable multiwavelength fiber laser with ultra-narrow wavelength spacing and
      large wavelength number using a semiconductor optical amplifier (SOA) has been
      demonstrated. Intensity-dependent transmission induced by nonlinear polarization
      rotation in the SOA accounts for stable multiwavelength operation with wavelength
      spacing less than the homogenous broadening linewidth of the SOA. Stable
      multiwavelength lasing with wavelength spacing as small as 0.08 nm and wavelength
      number up to 126 is achieved at room temperature. Moreover, wavelength tuning of
      20.2 nm is implemented via polarization tuning.

PMID- 19770940
TI  - Broad-spectrum, wavelength-swept, erbium-doped fiber laser at 1.55 microm.
AB  - We describe an argon-ion-laser-pumped erbium-doped fiber laser at 1.55 microm
      that incorporates low-rate frequency modulation of an intracavity acousto-optic
      modulator to provide repeated, continuous tuning of the output spectrum. The
      spectral width of this wavelength-swept fiber laser is as large as 20 nm with 9
      mW of output power, even though erbium in silica has a mostly homogeneously
      broadened gain. The time-averaged visibility curve for a 14-nm-wide source
      indicates a short (160-microm) coherence length, which is of interest for fiber
      optic gyroscopes that operate with long integration times and short-coherence
      length sources.

PMID- 19770941
TI  - Beryllium oxide: a frost-preventing insulator.
AB  - A method is suggested of achieving low outdoor radiative losses by low spectral
      emittance in the atmospheric window of 8-13 microm, which will reduce dew and
      frost formation on surfaces exposed to the clear sky. The use of this selectively
      low emittance makes it feasible to use electrically insulating materials. It is
      argued that lattice-based reststrahlen bands can be exploited for this purpose.
      The observation is made that hexagonal beryllium oxide has a strong reststrahlen
      band that covers most of the primary atmospheric window. Results from experiments
      with polycrystalline samples demonstrate that bulk beryllium oxide is equally
      effective for dew and frost prevention as glass coated with conducting tin oxide.

PMID- 19770942
TI  - Small-aperture, high-resolution, two-channel imaging system.
AB  - A method that utilizes incoherent light interferometry is used to form images
      through vanishingly small apertures. The method utilizes the increased channel
      capacity produced by reduction of spatial coherence, but in a way thatimproves
      the resolution instead of the signal-to-noise ratio.

PMID- 19770943
TI  - Transient picosecond response of the photorefractive effect in InP:Fe.
AB  - The time lag of the crossed-polarized part of the transmitted probe pulse, which
      is due to photorefractive energy transfer from the pump pulse, is measured with
      respect to the original transmitted probe pulse. The average photorefractive
      response time of the crystal is estimated through theoretical analysis.

PMID- 19770944
TI  - Quantum correlation and absorption spectroscopy in an optical parametric
      oscillator in the presence of pump noise.
AB  - We present a linearized quantum analysis of the optical parametric oscillator
      that includes the effects of pump noise. We show that excess pump noise reduces
      the intensity correlation between the signal and idler at low frequencies, which
      explains the low-frequency spectrum of current experimental observations. Its
      dependence on the cavity loss mismatch permits the possibility of ultrasensitive
      intracavity absorption spectroscopy, even in the absence of nonclassical
      correlation observation.

PMID- 19770945
TI  - Effect of the phase velocity and spatial overlap of spherical resonances on sum
      frequency generation in droplets.
AB  - The spectrum of the third-order sum-frequency generation (TSFG) that results from
      the electric fields of the laser E(omega(L)) and of the first-order Stokes
      stimulated Raman scattering E(omega(1s)) is dependent on the droplet radius. In
      addition to the amplitude and spatial overlap of the three generating E(omega)'s
      and of the generating and resultant waves, phase matching between the generating
      and TSFG waves is an important parameter. We discuss the range of phase
      velocities of the generating and TSFG waves, which must be tuned to coincide with
      spherical resonances in order to be guided waves circumnavigating the droplet
      rim.

PMID- 19770946
TI  - Almost all transmission grating self-pumped phase-conjugate mirrors are
      equivalent.
AB  - The photorefractive transmission grating ring self-pumped phase-conjugate mirror
      is shown to be formally equivalent to a double phase-conjugate mirror with
      internal losses and equal-intensity input beams. These mirrors are also
      equivalent to a self-pumped phase conjugator consisting of a photorefractive
      crystal with one face highly reflecting. This result shows that all transmission
      grating self-pumped phase-conjugate mirrors, with the exception of the linear
      self-pumped phase conjugator, are topologically equivalent to a double phase
      conjugate mirror. No similar equivalence can be shown for the reflection grating
      ring phase conjugator.

PMID- 19770947
TI  - Propagation loss in metal-clad waveguides and weakly absorptive waveguides by a
      perturbation method.
AB  - A simple and accurate perturbation method for the analysis of attenuation of
      guided modes in metal-clad waveguides and weakly absorptive waveguides is
      presented. The imaginary part N'' of the complex modal index N = N' + iN'' is
      obtained by solving the corresponding real eigenvalue equation and is given by
      partial differentialN'/ partial differentialepsilon' times epsilon'', where
      epsilon = epsilon' + iepsilon'' is the complex dielectric constant of the
      absorptive layer and partial differentialN'/ partial differentialepsilon' is
      obtained by numerical differentiation. The method is straightforward, and a
      cumbersome solution of complex transcendental equations is completely eliminated.
      Results for simple structures are in good agreement with those obtained by exact
      analysis.

PMID- 19770948
TI  - Monolithic integrated Nd:YAG laser.
AB  - By application of the technique of optical contact, a novel type of frequency
      stable solid-state laser resonator has been developed. A diode-laser-pumped,
      monolithic integrated twisted-mode-cavity Nd:YAG laser with 80 mW of single
      frequency output power at lambda = 1.06 microm has been fabricated. A linewidth
      below 10 kHz has been measured for the free-running laser.

PMID- 19770949
TI  - Nonreciprocal phase shifts in a femtosecond dye laser.
AB  - Beating is observed when the two output beams from a colliding-pulse mode-locked
      laser are recombined outside the cavity. This beating is attributed to nonlinear
      dephasing in the saturable absorber. An explanation in terms of the soliton
      period variation is given. The experimental results show good agreement with the
      predictions of the nonlinear Schrodinger equation.

PMID- 19770950
TI  - Low-energy ultrafast fiber soliton logic gates.
AB  - We have reduced the switching energy for an all-optical soliton dragging NOR gate
      to 5.8 pJ by using a two-fiber configuration and optimizing the fiber and laser
      parameters. The cascadable NOR gate has a fanout of six, restores both the logic
      level and timing, and can operate at bit rates of up to 0.2 THz. In addition, we
      show that soliton dragging can be represented as a generalized exclusive-or
      module with high functionality. Two such modules can be interconnected as NOR and
      AND gates or broadcast and routing switches.

PMID- 19770951
TI  - Reversibility and energetics in optical computing.
AB  - Computer operations that conserve energy do not, from an information viewpoint,
      increase entropy and therefore have no minimum energy cost associated with them.
      An information-conserving operation must be reversible in principle; reversible
      optical gates inevitably incur losses. The energy per calculation may have many
      meanings, as we show. The energy expended by a single photon in a conservative
      optical operation is negligible, much less than kT.

PMID- 19770952
TI  - Fast hybrid parallel carry look-ahead adder.
AB  - A new optical parallel arithmetic processing scheme using a nonholographic
      optoelectronic content-addressable memory (CAM) is discussed. The design of a
      four-bit CAM-based optical carry look-ahead adder (CLA) is presented. Compared
      with existing optoelectronic binary addition approaches, this nonholographic CAM
      scheme offers a number of practical advantages, such as faster processing speed
      and ease of optical implementation and alignment. For the addition of numbers
      longer than four bits, by incorporating the previous stages' carry, a number of
      four-bit CLA's can be cascaded. Experimental results are also presented.

PMID- 19770953
TI  - Method for planar measurement of temperature in compressible flow using two-line
      laser-induced iodine fluorescence.
AB  - A method for planar measurement of temperature in a compressible flow by means of
      two-line laser-induced iodine fluorescence is proposed. Temperature is determined
      from the ratio of the intensities of fluorescence, which are obtained by
      irradiation of two laser beams of different wavelength. Use of a high-sensitivity
      vidicon camera permits multiple-point measurements of temperature in the flow
      field. This method is applied to a supersonic free jet. It is found that the
      results obtained by P(16)/R(18) (514.720 nm) and P(26)/R(28) (514.942 nm)
      absorption lines in the transition of B(3)II(ou)+ (nu' = 43) ? X(1)sigma(g)+
      (nu'' = 0) can predict temperature below 300 K with an accuracy of +/-5K.

PMID- 19770954
TI  - Efficient optical enhancement of acousto-optic diffraction using optimized
      overlap of coupled waves.
AB  - We describe a technique by which the diffraction efficiency of an acousto-optic
      beam deflector may be substantially increased under high-power laser
      illumination. In earlier research we showed that the diffraction process is
      intrinsically associated with an intensity-dependent modification of the
      diffraction efficiency of an acousto-optic device. Here we show that this
      diffraction efficiency may be enhanced most effectively by distributing the
      optical intensity over the acousto-optic device in a manner that maximizes the
      overlap with the acoustic wave in the medium. In particular, we demonstrate
      increases in diffraction efficiency of greater than 80% in a TeO(2) device-an
      improvement of roughly an order of magnitude over earlier results in which this
      overlap technique was not used.

PMID- 19770955
TI  - Holographic sundial.
AB  - A holographic sundial, to our knowledge the first sundial that does not use a
      gnomen or shadow-casting device, is designed and demonstrated. The accuracy of
      the device is measured and analyzed.

PMID- 19770956
TI  - Second-harmonic generation of Er:YAG 2.94-microm laser radiation using an organic
      vinylidene cyanide/vinyl acetate thin film.
AB  - Frequency doubling of an Er:YAG laser beam is observed by using a vinylidene
      cyanide/vinyl acetate copolymer. The nonlinear susceptibility chi((2))(eff) is
      evaluated to be 5.6 x 10(-7) esu, which is 2.8 times larger than that of LiNbO(3)
      crystal. The dependence of the measured chi((2))(eff) on the poling process is
      analyzed based on a theoretical model.

PMID- 19770957
TI  - Three-wave and four-wave forward phase-conjugate imaging in photorefractive
      bismuth silicon oxide.
AB  - Phase-conjugate images in the forward direction are obtained by a new type of
      four-wave interaction and by the Heer-Griffin type of three-wave interaction. The
      nonlinear medium is bismuth silicon oxide in which the interaction is optimized
      by detuning the input beam(s). Measurements are made for several test objects and
      interbeam angles.

PMID- 19770958
TI  - Moving grating and intrinsic electron-hole resonance in two-wave mixing in
      photorefractive InP:Fe.
AB  - The theory for two-wave mixing in photorefractive InP:Fe under a dc electric
      field with both electron-hole intrinsic resonance and a moving grating is
      developed. An extended resonance condition is predicted. The phenomenon is proved
      experimentally, even though a quantitative discrepancy remains between theory and
      experiments.

PMID- 19770959
TI  - Real-time generation of the Wigner distribution of complex functions using phase
      conjugation in photorefractive materials.
AB  - An optical processor for real-time generation of the Wigner distribution of
      complex amplitude functions is introduced. The phase conjugation of the input
      signal is accomplished by a highly efficient self-pumped phase conjugator based
      on a 45 degrees -cut barium titanate photorefractive crystal. Experimental
      results on the real-time generation of Wigner distribution slices for complex
      amplitude two-dimensional optical functions are presented and discussed.

PMID- 19770960
TI  - Nonlinearity-induced resonances and optical multistability with coupled surface
      plasmons in a symmetric layered structure.
AB  - We present the exact numerical results for optical multistability with surface
      plasmons coupled through a dielectric slab with isotropic Kerr-type nonlinearity.
      We show the possibility of having multivalued output with both the long- and
      short-range modes and discuss the field profiles in the nonlinear medium.
      Moreover, we show the existence of nonlinearity-induced resonances in the
      structure that are missing in the linear theory.

PMID- 19770961
TI  - Wavelength dependence of bending loss in monomode optical fibers: effect of the
      fiber buffer coating.
AB  - The bend-induced optical loss in a monomode fiber has been studied as a
      continuous function of wavelength in the range 1.2-1.6 microm. The loss was
      observed to be an oscillatory function of wavelength. These observations were
      explained by using a model based on interference between the guided core mode in
      the fiber and a "whispering gallery" mode ejected from the core by the bend. The
      wavelengths of the minima in the oscillatory function were accurately predicted
      by the model when the propagation of optical power in the fiber buffer coating
      was taken into account.

PMID- 19770962
TI  - Laser-fabricated fiber-optic taps.
AB  - A CO(2)-laser-based laser ablative chemical etching (LACE) technique was used for
      the rapid (milliseconds) fabrication of micrometer-scale taps in the cladding of
      multimode silica optical fibers. In the initial experiments the optical-quality
      surfaces of the etched groove directionally radiate approximately one third of
      the total tap output. The fraction of the guided optical energy tapped out can be
      easily and precisely controlled by the laser parameters. The radiation patter
      from the tap is in reasonably good agrement with initial theoretical
      calculations. This novel LACE-based tap manufacturing technique permits computer
      controlled, rapid, and inexpensive fabrication of the high-quality fiber-optic
      taps needed for realizing various fiber-optic signal-processing, interconnection,
      monitoring, and sensor systems.

PMID- 19770963
TI  - Ultraviolet light photosensitivity in Ge-doped silica fibers: wavelength
      dependence of the light-induced index change.
AB  - A novel technique is reported for detecting permanent and transient light-induced
      refractive-index changes (photosensitivity) in optical fibers. The index change
      is detected by irradiating one arm of an unbalanced Mach-Zehnder fiber
      interferometer with UV light, thereby changing its optical path length. From a
      measurement of the change in the spectral response of the Mach-Zehnder
      interferometer, the change in the fiber core index as a function of wavelength
      can be determined. The equilibrium change in the core index is found to have an
      almost constant value of approximately 2.3 x 10(-5) over the measured wavelength
      range of 700 to 1400 nm.

PMID- 19770964
TI  - Nonlinearity difference in the two passbands of a distributed-feedback
      semiconductor laser amplifier.
AB  - The nonlinearity difference in the two passbands of a distributed-feedback
      semiconductor laser amplifier was studied experimentally. A theoretical
      explanation was given by using the transmission matrix approach. The difference
      of nonlinearity in the two passbands was found to be enhanced greatly by the
      mechanism of asymmetric facet reflection.

PMID- 19770965
TI  - TEM(00)-mode and single-longitudinal-mode laser operation with a cholesteric
      liquid-crystal laser end mirror.
AB  - We describe the unique properties of a cholesteric liquid crystal as a laser end
      mirror. We show how it gives rise to TEM(00)-mode operation as well as single
      longitudinal-mode operation of a solid-state laser resonator.

PMID- 19770966
TI  - Two-gigahertz repetition-rate, diode-pumped, mode-locked Nd:YLF laser.
AB  - A diode-pumped Nd:YLF laser has been acousto-optically mode locked at a 2-GHz
      repetition rate, giving pulse widths of 7 psec with an average power of 135 mW at
      a wavelength of 1.047 microm. The 2-GHz pulse rate corresponds to a free-space
      cavity length of 7.5 cm, while the laser's actual cavity length is approximately
      6.6 cm. The mode locker consists of a sapphire substrate with a lithium niobate
      transducer, giving 0.5% loss modulation per watt. Stable mode-locked pulses were
      achieved for loss modulations of 1% or greater.

PMID- 19770967
TI  - Self-phase-modulation-controlled passively mode-locked dye laser.
AB  - We demonstrate a laser that permits self-phase modulation to be controlled
      independently of other parameters in a colliding-pulse mode-locked laser system.
      With this laser system, pulse compression by a factor of 1.5 was observed, and a
      stronger soliton effect was found.

PMID- 19770968
TI  - Passive mode locking of a laser with a nonlinear fiber reflector.
AB  - A nonlinear mirror in the form of a fiber-loop reflector with nonreciprocity is
      proposed as a passive mode locker. The mode-locking process occurs as a result of
      the interference of counterpropagating pulses, when they are properly chirped in
      the fiber loop. With a computer simulation, we study a simple one-cavity model
      and find stable solutions.

PMID- 19770969
TI  - Broadly tunable femtosecond pulses generated by optical parametric oscillation.
AB  - A singly resonant optical parametric oscillator is demonstrated that uses a beta
      barium borate crystal and is synchronously pumped by microsecond pulse trains of
      a Nd:glass laser (0.8 psec, 527 nm). Broadly tunable pulses are generated in the
      wavelength range 0.7-1.8 microm with a duration of 160-260 fsec and an energy
      conversion of 3%. Steep pulse wings are observed, with a 1/e decay time of
      approximately 90 fsec. Under special conditions, parametric pulses as short as 65
      +/- 7 fsec are obtained.

PMID- 19770970
TI  - Noise characterization of femtosecond color-center lasers.
AB  - We used power-spectrum techniques to measure both amplitude noise and timing
      jitter of two femtosecond colorcenter lasers in the near infrared: a passively
      mode-locked laser and an additive-pulse mode-locked laser. The cw pumped
      passively mode-locked color-center laser showed better noise performance than the
      feedback-controlled, much more complex additive-pulse mode-locked color-center
      laser. For both laser systems, we observed unexpected drastic increases of
      amplitude noise under certain operation conditions. In the low-noise operation
      regime, the amplitude noise of the passively mode-locked color-center laser is
      entirely dominated by its pump laser, whereas the additive-pulse mode-locked
      laser exhibits >10 dB of excess noise up to 200 kHz and tended to break up in the
      subhertz regime. The timing jitter for both lasers was approximately 9 psec rms
      for jitter rates above 130 Hz.

PMID- 19770971
TI  - Real-time restoration method for image transmission in a multimode optical fiber.
AB  - A new restoration method for a distorted image transmitted through a single step
      index multimode fiber is presented. The transmission of the reference beam along
      with the image enables one to compensate on a real-time basis for the distortion
      caused by the fiber modal phase dispersion. At the receiver end the interference
      between the Fourier-transformed image and the reference beam creates gratings in
      a photorefractive crystal. It is theoretically shown that, owing to the spatial
      segregation characteristic of the Fourier-transformed mode distribution of the
      step-index fiber, the phase conjugation of thetransmitted image through four-wave
      mixing obtained from the crystal reconstructs the original image.

PMID- 19770972
TI  - Effect of the pumping geometry on the half-widths of the lasing peaks observed
      from Rhodamine 6G ethanol droplets.
AB  - The effect of the pumping intensity and geometry and the dye concentration on the
      lasing spectra from Rhodamine 6G ethanol droplets pumped with a high-power pulsed
      laser is investigated. The observed lasing peaks are found to broaden slowly
      whenthe pump intensity and dye concentration are increased. Significantly
      different spectra may be observed by pumping with a beam of diameter less than
      the droplet size.

PMID- 19770973
TI  - Raman heterodyne detection of electron paramagnetic resonance.
AB  - We report the detection of an electron paramagnetic resonance signal using Raman
      heterodyne spectroscopy, a rf -optical double-resonance technique. The signals
      are associated with the nitrogen-vacancy center in diamond, which has a spin
      triplet ground state. A three-line spectrum associated with the nitrogen
      hyperfine structure is observed for various magnetic field strengths and crystal
      orientations.

PMID- 19770974
TI  - Mirrorless optical bistability in a nonlinear absorbing dielectric film.
AB  - The optical transmissivity of a mirrorless, nonlinear, absorbing dielectric thin
      film is investigated numerically. The dielectric function in the film region is
      dependent on the intensity of the electromagnetic field. Multivalued solutions of
      transmissivity as a function of incident power are calculated for the steady
      state wave equation. The numerical solution is applied to two different model
      dielectric functions. As the absorption parameter is increased, larger values of
      incident intensity are required to switch the systems between stable output
      states. Also, the peak values of transmissivity are reduced as the absorption is
      increased.

PMID- 19770975
TI  - Raman heterodyne detection of electron paramagnetic resonance.

PMID- 19770976
TI  - Intensity-activated birefringence zero-crossing shift in CuAlSe(2) crystal.
AB  - We describe a new nonlinear-optical phenomenon called the intensity-activated
      birefringence zero-crossing shift. This phenomenon leads to the shift of the
      transmission curve of the gyrotropic isoindex spectral filter. The phenomenon was
      observed with 33-psec, 532-nm Nd(3+):YAG laser pulses in CuAlSe(2) semiconductor
      crystal. An anisotropic refractive-index nonlinearity with an approximately 200
      psec switch-off time is responsible for the shift. Possible applications for
      light by light-control devices are discussed.

PMID- 19770977
TI  - Optical-damage-resistant LiNbO(3):Zn crystal.
AB  - Zinc doping is shown to reduce the photorefraction in LiNbO(3):Zn. The damage
      resistant crystal LiNbO(3):Zn has demonstrated a conversion efficiency of
      approximately 50% for frequency doubling of 1.06-microm radiation. The dependence
      of optical characteristics on the ZnO concentration in the melt reveals a sharp
      change of the optical properties at the threshold concentration of 4-6 mol % Zn.
      The optical and nonlinear-optical data of LiNbO(3):Zn are similar to those of
      LiNbO(3):Mg, but the former shows better optical performance.

PMID- 19770978
TI  - Cerenkov doubling of infrared radiation in a planar waveguide loaded by an
      organic thin film.
AB  - Frequency doubling of infrared coherent radiation in a planar waveguide loaded by
      an organic thin film is described. By using a strongly nonlinear crystal, such as
      2-methyl-4-nitroaniline, as the loading organic material, more secondharmonic
      radiation can be expected than that reported in a proton-exchanged or Ti-diffused
      LiNbO(3) waveguide. The electromagnetic field analysis shows that the selection
      of a cover material that bounds the surface of the organic film is important in
      fulfilling the Cerenkov condition.

PMID- 19770979
TI  - Stimulated four-photon mixing with crossed pump dividing in an optical fiber.
AB  - An experimental study of stimulated four-photon mixing with crossed pump dividing
      in a birefringent optical fiber is described. The interactive four photons are
      all in the same mode but with different polarizations. The pump wave is
      distributed in two orthogonal linear polarizations, and the polarizations of
      Stokes and anti-Stokes waves are also orthogonal. It is shown that the Stokes
      shift of this stimulated four-photon mixing process is related not only to the
      material dispersion but also to the waveguide dispersion and is directly
      proportional to the birefringence.

PMID- 19770980
TI  - Solitons and two-photon absorption.
AB  - The effect of weak two-photon absorption on soliton propagation is investigated.
      It is found that fundamental solitons evolve adiabatically; expressions
      describing their broadening and attenuation are given. Higher-order solitons
      break up into two diverging fundamental solitons for a wide range of parameters.

PMID- 19770981
TI  - Transition excitation at 0.9 microm by multiphoton pumping of Nd(3+)-doped
      fibers.
AB  - Multiwavelength oscillations near 0.9 microm (i.e., 0.88-0.98 microm) have been
      obtained in a Nd(3+)-doped silica-based single-mode optical fiber. The laser pump
      wavelength is 1.064 microm, with an average pump power of approximately 1.8
      GW/m(2). The observed emission rate has reached a few percent. We discuss the
      possibility that this fluorescence or perhaps superfluorescence arises by
      multiphoton absorption.

PMID- 19770982
TI  - Short-pulse pumping of a recombination Balmer-alpha laser of hydrogenic sodium.
AB  - A NaF foil target was irradiated at an intensity of 6.0 x 10(14) W/cm(2) with a
      28-psec, 526-nm, 23-J laser pulse. A space- and time-averaged gain coefficient of
      4 +/- 1 cm(-1) was obtained for Na XI H-alpha at 5.42 nm. Computer simulation
      gives a peak time- and space-resolved gain of ~18 cm(-1).

PMID- 19770983
TI  - Q-switched Nd:YLF laser end pumped by a diode-laser bar.
AB  - We describe 20-kW operation of a Q-switched Nd:YLF laser end pumped by a 5-mJ, 25
      W quasi-cw diode-laser bar. A fiber coupler was used to adapt the 1-cm-wide
      active area of the diode-laser bar to the circular shape of the TEM(00) mode. The
      maximum 1047-nm TEM(00) output energy was 0.5 mJ in a 22-nsec Q-switched pulse.
      This corresponds to a peak power in excess of 20 kW and was obtained at an
      optical slope efficiency of 13%.

PMID- 19770984
TI  - Pumping dye lasers by optical fibers: a simple and efficient device.
AB  - The performance of a pulsed dye laser pumped through optical fibers by the second
      harmonic of a Nd:YAG laser is systematically studied by using a simple design. A
      single fiber (1-mm core) readily gives dye pulse energies in the millijoule per
      pulse range, with an efficiency of as much as 50% using improvable optics. Pulse
      time lengthening and delayed two-pulse operation are studied by using a dual
      fiber device.

PMID- 19770985
TI  - Q-switched laser at 912 nm using ground-state-depleted neodymium in yttrium
      orthosilicate.
AB  - A ground-state-depleted laser is demonstrated in the form of a Q-switched
      oscillator operating at 912 nm. By using Nd(3+) as the active ion and Y(2)SiO(5)
      as the host material, the laser transition is from the lowest-lying Stark level
      of the Nd(3+4)F(?) level to a Stark level 355 cm(-1) above the lowest-lying one
      in the (4)I(9/2) manifold. The necessity of depleting the ground (4)I(9/2)
      manifold is evident for this level scheme as transparency requires a 10%
      inversion. To achieve the high excitation levels required for the efficient
      operation of this laser, bleach-wave pumping using an alexandrite laser at 745 nm
      has been employed. With KNbO(3), noncritical phase matching is possible at 140
      degrees C using d(32) and is demonstrated.

PMID- 19770986
TI  - Degenerate cross-phase modulation for pulse compression and amplification of
      ultrashort laser pulses.
AB  - Temporal and spectral profiles of a linearly polarized ultrashort laser pulse
      modulated by a copropagating perpendicularly polarized strong laser pulse with
      the same frequency in condensed matter have been modeled. Degenerate cross-phase
      modulation can be applied to femtosecond optical pulse compression and
      amplification without the use of gratings or prisms and to signal processing
      owing to the small walk-off and the degenerate four-wave mixing between the pump
      and probe pulses. In a double pump compression case, the pulse duration of the
      probe pulse has been reduced by a factor of 15 with the energy gain of over
      fourfold. This result gives a power gain of 60-fold.

PMID- 19770987
TI  - Amplitude noise reduction of 50 dB in colliding-pulse mode-locking dye lasers.
AB  - Spurious sidebands observed in the noise spectrum of colliding-pulse mode-locking
      dye lasers result from coupling of the longitudinal mode beating modulations of
      the (argon-ion) pump laser with the dye laser. We achieve a 50-dB amplitude noise
      reduction at the mixing frequencies by inserting a single-frequency etalon in the
      argon-laser cavity. Furthermore, we find the amplitude noise of the colliding
      pulse mode-locking laser to be entirely dominated by the (plasma discharge) noise
      of the argon laser.

PMID- 19770988
TI  - High-efficiency joint-transform correlator.
AB  - A technique that increases the efficiency of a conventional joint-transform
      correlator is proposed. By modifying the joint-transform power spectrum of the
      input objects by using a spatial sampling method, the readout light as well as
      the physical area of the square-law detector can be fully utilized. As a result,
      the output correlation intensity can be substantially increased. Cases of using
      coherent and partially coherent readout light are discussed, and experimental
      results are presented.

PMID- 19770989
TI  - Analogue of the van Cittert-Zernike theorem for statistically homogeneous wave
      fields.
AB  - A theorem is presented that expresses a correspondence between the degree of
      spatial coherence of statistically homogeneous fields and the complex amplitude
      in certain monochromatic fields. The theorem is illustrated by an example that
      shows the behavior of the degree of spatial coherence of certain partially
      coherent fields throughout a three-dimensional volume region.

PMID- 19770990
TI  - Information erasing in the phenomenon of long-lived photon echo.
AB  - The possibility of erasing information in an arbitrary cell of an optical memory
      device based on the phenomenon of long-lived photon echo is theoretically
      considered. Optimal conditions for a maximal number of write-erase cycles in a
      given cell are obtained, and an experimental setup for observing this effect is
      proposed.

PMID- 19770991
TI  - Distributed-temperature sensing using stimulated Brillouin scattering in optical
      silica fibers.
AB  - Temperature distribution in silica single-mode optical fibers, from -30 to +60
      degrees C, is successfully measured by using Brillouin optical-fiber time-domain
      analysis. A temperature measurement accuracy of 3 degrees C with a spatial
      resolution of 100 m is attained over a fiber length of 1.2 km.

PMID- 19770992
TI  - Thin-metal-clad waveguide polarizers: analysis and comparison with experiment.
AB  - We present an analysis of a thin-metal-film in-line fiber polarizer and compare
      the results with experimentally observed TE- and TM-mode losses. It is shown that
      the analysis predicts reasonably well the experimentally observed behavior. The
      present analysis can be used as a design aid for obtaining initial design
      parameters such as buffer thickness, type of metal, metal thickness, and
      superstrate refractive index for such polarizer structures.

PMID- 19770993
TI  - Magnetic-field-induced birefringence in a homeotropic ferronematic liquid-crystal
      wedge.
AB  - The magnetic-field-induced birefringence in wedged homeotropic ferronematic
      liquid crystals is studied. Theoretical results for small distortions are
      obtained in terms of the elastic continuum theory of liquid crystals. The results
      of birefringence measurements are in good agreement with the predictions of the
      theory.

PMID- 19770994
TI  - Polarization corrections of dispersion characteristics of optical waveguides.
AB  - The polarization corrections to optical waveguide dispersion characteristics from
      the scalar wave equations are calculated by an improved perturbation formula and
      a vector variational expression. More-accurate predictions than with the
      conventional first-order perturbation theory are demonstrated.

PMID- 19770995
TI  - Polarization dynamics of counterpropagating beams in optical fibers.
AB  - We study the temporal dynamics of the polarization state of counterpropagating
      waves in nonlinear-optical fibers, including the effects of birefringence. In the
      presence of uniform twist, the dynamics may be reduced to an integrable chiral
      field representation. The stability analysis reveals the temporally stable
      polarization configurations or ground states. Polarization switching between
      these states may occur through domain wall solitons.

PMID- 19770996
TI  - Nonclassical intensity correlation from a type I phase-matched optical parametric
      oscillator.
AB  - Signal and idler beams from a type I phase-matched nondegenerate optical
      parametric oscillator are separated by a Mach-Zehnder interferometer. Broadband
      nonclassical intensity correlation is observed, in agreement with a theory that
      includes pump noise. The maximum observed correlation, which occurs at 1.1 MHz,
      yields a noise level 2.8 dB below the shot noise.

PMID- 19770997
TI  - Ultrashort-soliton interactions in optical fibers.
AB  - The redistribution of energy between two interacting femtosecond-range solitons
      is numerically observed by solving the generalized nonlinear Schrodinger equation
      by a modified version of the beam-propagation method. The energy redistribution
      depends on various input parameters such as the relative phase, wavelength
      difference, relative intensity, and temporal separation between the two solitons.
      The dependence of the initial relative phase is discussed in detail, and the
      mechanism of the interactions is also discussed. The energy redistribution has
      the potential for the applications to ultrafast switching devices and logic
      gates.

PMID- 19770998
TI  - Signal-to-noise considerations in fiber links with periodic or distributed
      optical amplification.
AB  - The detected signal-to-noise power ratio is evaluated for fiber links with
      periodic amplification. It is shown that the highest ratio is achieved in the
      limit of a distributed amplifier (g = alpha), but that, alternatively, periodic
      amplification at intervals of alpha(-1) entails a penalty of less than 2 dB
      compared with the (ideal) distributed case.

PMID- 19770999
TI  - Quasi-deterministic theory of semiconductor-laser gain switching.
AB  - The anomalous enhancement of fluctuations during gain switching of semiconductor
      lasers is considered. An extension of the quasi-deterministic theory is performed
      to account for the nonlinear dynamics of the process. The results are in
      quantitative agreement with those of a computer simulation of the Langevin rate
      equations describing the process.

PMID- 19771000
TI  - Compact mode-locked solid-state lasers at 0.5- and 1-GHz repetition rates.
AB  - A compact laser system that combines a GaP mode locker and a diode-pumped Nd:YAG
      laser to produce 1064-nm pulses at 0.5- and 1-GHz repetition rates is described.
      Extension of this research using a Ti:sapphire-pumped Nd:YLF laser is also
      presented. Stable optical 1047-nm pulses with durations of 6.2 psec at a l-GHz
      repetition rate have been produced.

PMID- 19771001
TI  - Energy storage in quantum-well lasers.
AB  - A new scheme of energy storage in single-quantum-well semiconductor lasers is
      analyzed. This scheme involves the storage of the majority of injected carriers
      in the continuum states of the surrounding bulk material, in which the carrier
      density is diluted and the higher-order carrier-density-dependent recombination
      processes are much smaller. This allows the inversion level to build up to a much
      higher level during the pumping stage of Q switching. The possibility of using
      indirect-band-gap semiconductors for carrier storage is also proposed.

PMID- 19771002
TI  - Ultrashort-pulse propagation in optical fibers.
AB  - A more exact model is suggested for the description of nonlinear light
      propagation in fibers. In addition to the previously discussed self-phase
      modulation, parametric, dispersion, self-steepening, and Raman self-scattering
      effects, this model also takes into account the Stokes losses associated with the
      material excitation, the dependence of nonlinear effects on the light frequency,
      and the frequency dependence of the fiber mode area. The self-steepening effect
      is taken into account more correctly in comparison with previous models. The
      effects influence considerably the femtosecond soliton propagation. The model is
      generalized for the case of various fiber dispersion properties along the fiber
      length. The possibility of obtaining high-quality pulses of less than 15-fsec
      duration by compression of fundamental solitons with approximately 100-fsec
      duration in fibers with slowly decreasing dispersion is shown.

PMID- 19771003
TI  - Chirp and self-phase modulation in induced-grating autocorrelation measurements
      of ultrashort pulses.
AB  - We show that induced-grating/four-wave-mixing ultrashort-pulse autocorrelation
      techniques that use slowly responding media offer the same phase information as
      interferometric second-harmonic generation. We also show that autocorrelation
      traces from nearly all possible induced-grating/four-wave-mixing beam geometries
      provide this information, with all yielding the same theoretical result, an
      integral of a fourth-order electric-field coherence function. Such traces clearly
      reveal chirp and self-phase-modulation effects without high-frequency fringes.
      Experiments using a two-beam-coupling arrangement in photorefractive media
      illustrate these effects.

PMID- 19771004
TI  - Self-starting additive-pulse mode locking of a Nd:glass laser.
AB  - Self-starting cw mode-locked operation of a Nd:glass laser has been achieved by
      using a nonlinear external resonator. The coupled cavity incorporating an optical
      fiber initiates and sustains ultrashort-pulse generation, resulting in a stable
      train of 380-fsec pulses.

PMID- 19771005
TI  - Parallel multiple matrix multiplication using an orthogonal shadow-casting and
      imaging system.
AB  - A novel orthogonal shadow-casting and imaging optical system is proposed for
      performing multiple matrix multiplication. An analysis is given for describing
      the construction of a matrix processor. Preliminary experiments of matrix
      multiplication are demonstrated.

PMID- 19771006
TI  - Array interconnection by phase-coded optical correlation.
AB  - We present an algorithm for optical interconnection of two-dimensional arrays by
      transmitting the input through a phase-code mask then correlating it with a
      control image constructed from the interconnection weights. An arbitrary complex
      weighted interconnection pattern can be encoded. We show how the output signal-to
      noise ratio can be traded for control image size and complexity by adjusting the
      phase-code feature size. Theoretical calculations of the average output signal-to
      noise ratio are compared with computer simulations of the algorithm.

PMID- 19771007
TI  - Combined associative memories.
AB  - One of the major problems with conventional associative memory models is that
      there exists a set of stable false and oscillatory states in addition to the true
      memories in the models. To solve this problem, a combined associative memory
      model is proposed. Digital simulation results show that the model is capable of
      picking out the false memories generated by conventional models and is more
      reliable in comparison with the conventional models.

PMID- 19771008
TI  - Raman heterodyne detected electron-nuclear-double-resonance measurements of the
      nitrogen-vacancy center in diamond.
AB  - We report two new applications of the Raman heterodyne detection technique. Raman
      heterodyne detected electron-nuclear double resonance and a double rf resonance
      technique are used to obtain the hyperfine structure of the nitrogen-vacancy
      center in diamond.

PMID- 19771009
TI  - Continuous spatial photon echoes.
AB  - We report the observation of continuous spatial photon echoes in a magnetically
      compensated supersonic beam of atomic samarium. Atoms cross two spatially
      separated cw laser pump fields to produce an intense cw echo downstream. In
      contrast to previous studies of continuous coherent radiation in separated
      fields, the signals are readily observable with the unaided eye. The echo signal,
      which is generated in a magnetic-field gradient, differs from usual rephasing
      phenomena owing to a quadratic time dependence for the optical phase in the frame
      of the moving atoms.

PMID- 19771010
TI  - Optical-fiber temperature sensor based on upconversion-excited fluorescence.
AB  - The codoping of a heavy-metal fluoride glass by two rare-earth ions, erbium and
      ytterbium, permits the semiconductor laser infrared excitation of two visible
      neighboring fluorescence lines of erbium by upconversion, the intensity ratio of
      which is a single variable function of temperature.

PMID- 19771011
TI  - Sensitivity-enhancing scheme of a polarimetric heterodyne sensor using a
      birefringent fiber loop.
AB  - In order to improve the sensitivity of a fiber-optic polarimetric sensor, a new
      scheme utilizing a birefringent fiber loop with midloop frequency shifters is
      proposed. In this scheme, heterodyne signals with an integral multiple-phase
      sensitivity can be obtained in the frequency domain. The validity of the scheme
      is confirmed experimentally by a bulk-optic configuration. One-order-of-magnitude
      improvement in sensitivity without changing the dynamic range is expected from
      the calculation of the signal-to-noise ratio, even in the case of a 40% excess
      loss in the optical loop.

PMID- 19771012
TI  - Electric-field-modulated light scattering near a morphological resonance of a
      trapped aerosol particle.
AB  - We describe electric-field-induced fluctuations in the elastic scattering near
      optical resonances of a spherical aerosol particle trapped at the null point of
      an electrodynamic levitator. The particle is apparently driven into a quadrupolar
      distortion by the electromechanical stress at its surface. Our results coupled
      with recent theory indicate that the effect is principally due to a modulation in
      the frequencies of individual optical resonances, that a coherent distortion
      smaller than one part in 10(5) ( approximately 0.1 nm) is detected, and that the
      effect may be used for a continuous probe of surface tension and bulk viscosity.

PMID- 19771013
TI  - High-speed, low-power optical phase conjugation using a hybrid amorphous
      silicon/ferroelectric-liquid-crystal device.
AB  - Optical phase conjungation using an amorphous silicon/ferroelectric-liquid
      crystal light modulator shows an optical response of 100 microsec with a
      diffraction efficiency of 8.5% for an incident optical intensity of 1 mW/cm(2).

PMID- 19771014
TI  - Saturable absorption, wave mixing, and phase conjugation with bacteriorhodopsin.
AB  - Bacteriorhodopsin exhibits strong nonlinear and saturation behavior with very low
      light intensities (~10 mW/cm(2)). A model and an experimental study of the
      saturation are described. Four-wave mixing experiments are used for obtaining
      phase conjugation and information on the holographic resolution of the material.
      Two kinds of samples were prepared and used in the experiments: films of
      bacteriorhodopsin in a solid polyvinylalcohol (polymer) matrix and in water.

PMID- 19771015
TI  - Two-dimensional poling of organic and polymer films for improved nonlinear
      optical properties.
AB  - Nematic films doped with molecules of high nonlinear polarizability can exhibit
      two-dimensional asymmetry after electric-field poling along one direction only.
      Consequently, these films exhibit more nonzero components of the second-order
      susceptibility tensor than are obtained through usual poling techniques. These
      films can exhibit very high nonlinear optical coefficients (close to 10(-7)
      esu/cm(3)) and retain most of their nonlinearity one week after removal of the
      poling field.

PMID- 19771016
TI  - Nonlinear photonic switching by using the spatial soliton collision.
AB  - We introduce a novel device for optical switching by using the position shift of
      the spatial soliton after collision. The device is a one-to-three switching
      device controlled by two control beams. For the optimum signal power, the
      transmission efficiency is above 95%. The wave propagation in the structure and
      the transmission efficiency as a function of input signal power are shown and
      discussed.

PMID- 19771017
TI  - Measurement of third-order optical nonlinear susceptibility using four-wave
      mixing in a single-mode ridge waveguide.
AB  - Nondegenerate four-wave mixing in a single-mode ridge waveguide has been
      demonstrated as a technique for simultaneous measurement of the imaginary
      component and the absolute magnitude of the third-order nonlinear susceptibility
      chi((3)). In the same experimenal apparatus, Im chi((3))(omega(2) = omega(1) +
      omega(2) - omega(1)) was obtained by measuring the pump-induced probe power loss
      and |chi((3))(omega(3) = omega(1) + omega(1) - omega(2))| was derived from Stokes
      wave generation efficiency. The ratio of these quantities was obtained without
      significant system uncertainties. The technique has been applied to AlGaAs/GaAs
      quantum-well waveguides with picosecond laser pulses. For homega(1) approximately
      homega(2) approximately 1.43 eV, it was found that Im chi((3)) = (6.1 +/- 0.5) x
      10(-11) esu, |chi((3))| = (7.6 +/- 1.7) x 10(-11) esu with a system uncertainty
      of 25%, and Im chi((3))/|chi((3))| = 0.8 +/- 31%, indicating the dominance of two
      photon absorption.

PMID- 19771018
TI  - Optical frequency division using an optical parametric oscillator.
AB  - A novel method of frequency division based on optical parametric oscillation is
      proposed. This scheme converts with high efficiency an input signal into two
      intense, coherent subharmonic outputs whose frequencies are tunable and whose
      linewidths are essentially limited by the input pump linewidth. By locking their
      difference frequency to a microwave, a millimeter-wave, or an infrared reference
      source, the output frequencies are precisely determined. The proposed frequency
      dividers can be operated in series or in parallel to measure, compare, and
      synthesize frequencies from optical to microwave. A line-narrowing effect for the
      generation of ultrastable radiation is discussed.

PMID- 19771019
TI  - Polarization-resolved coherent transient beam combination in optical Kerr media.
AB  - We have observed transient, coherent beam combination by degenerate two-wave
      mixing of frequency-doubled Nd:YAG picosecond laser pulses in carbon disulfide,
      using a circularly polarized pump wave and a linearly polarized probe beam. The
      important role of beam polarization is observed, and its part in energy transfer
      is discussed. A theory that treats polarization effects in transient two-wave
      mixing is presented, applied to the carbon disulfide experiments, and found to be
      in excellent agreement with the data.

PMID- 19771020
TI  - Analysis of chromatic dispersion properties of triple-clad fibers by coupling
      mode theory.
AB  - A model based on coupling-mode theory, for the quantitative analysis of chromatic
      dispersion characteristics of triple-clad single-mode fibers, is proposed. The
      strong wavelength dependence of the coupling between a core mode and a ring mode
      supported by the high-index second cladding of the waveguide structure is shown
      to be responsible for the dispersion-flattened characteristics of the fiber.
      Cutoff properties of this type of fiber are also analyzed according to the
      proposed model.

PMID- 19771021
TI  - Ultraviolet-light photosensitivity in Er(3+)-Ge-doped optical fiber.
AB  - Light-induced refractive-index change in Er(3+)-Ge-doped optical fiber is
      reported for the first time to the authors' knowledge. Evidence of the change is
      observed when UV light (lambda = 249 nm) irradiates one arm of an unbalanced Mach
      Zehnder interferometer made from Er(3+)-Ge-doped fiber. From a measurement of the
      change in the spectral response of the interferometer with UV exposure, the
      change in fiber core index as a function of wavelength is determined. The
      equilibrium change in core index is found to vary between 2.3 x 10(-5) and 3.7 x
      10(-5) over the measured wavelength region of 800 to 1700 nm. Also for the first
      time to our knowledge, fused couplers made of Er(3+)-doped fiber are reported.
      These identical fiber couplers are used in a novel all-fiber unbalanced Mach
      Zehnder interferometer.

PMID- 19771023
TI  - Phase jitter in an injection-locked semiconductor laser.
AB  - An expression for the mean-square phase jitter of an injection-locked
      semiconductor laser is derived. It leads to the determination of the power
      spectrum of the locked laser. The theoretical results are in good agreement with
      experimental results reported previously [IEEE J. Quantum Electron. 24, 148
      (1988)].

PMID- 19771022
TI  - Elimination of chaos in an intracavity-doubled Nd:YAG laser.
AB  - We predict theoretically a stable configuration for the operation of a multimode,
      intracavity-doubled, diode-pumped Nd:YAG laser. Experimental results are
      presented that demonstrate the elimination of chaotic amplitude fluctuations by
      rotatory alignment of the KTP crystal.

PMID- 19771024
TI  - Femtosecond KCl:Li and RbCl:Li color-center lasers near 2.8 microm with a HgCdTe
      multiple-quantum-well saturable absorber.
AB  - We have used HgCdTe multiple-quantum-well saturable absorbers to passively mode
      lock KCl:Li and RbCl:Li color-center lasers and have generated pedestal-free
      pulses as short as 120 fsec near 2.8 microm. To our knowledge, these are the
      shortest pulses in this wavelength range, and our laser is the only direct source
      of subpicosecond pulses in the mid-infrared region. Our results generalize the
      semiconductor passive mode-locking technique to different wavelength ranges,
      saturable absorber materials, and laser systems and are consistent with a model
      in which LO phonon collisions determine the fast saturable absorber behavior.

PMID- 19771025
TI  - Liquid crystal 1 x N optical switch.
AB  - The design, experimental results, and analysis of a 1 x N ferroelectric liquid
      crystal optical switch based on polarization rotation are reported. The switch is
      broadband and tolerant to errors in the ferroelectric liquid-crystal tilt angle
      and cell thickness. Moreover, the cross talk in the switch is noncumulative and
      independent of the switch size N. The results of an experimental 1 x 4 switch are
      presented. The switch has a signal-to-cross-talk ratio ranging from 21.6 to 37.1
      dB, a switching time of 50 microsec, and a worst-case insertion loss of 3.5 dB.

PMID- 19771026
TI  - Broadband squeezing of light by pulse excitation.
AB  - Broadband squeezed states of the electromagnetic field are generated by
      degenerate parametric downconversion with pulse-light excitation in a
      Ba(2)NaNb(5)O(15) crystal, in which noncritical type I phase matching is
      attained. Noise reduction below the level of the vacuum fluctuation is clearly
      observed over a detection bandwidth from dc to approximately 70 MHz. The minimum
      noise level obtained in the quiet quadrature is 1.1 dB below the shot-noise
      level. The scheme used in the present experiment is simple and promising for
      further improvement of squeezing. The relation between squeezing and parametric
      fluorescence is discussed quantitatively for the first time to the authors'
      knowledge.

PMID- 19771027
TI  - Wideband long-pulse operation of an efficient electro-optic modulator at 10.6
      microm.
AB  - High conversion efficiency over a wide microwave band has been achieved in a high
      power CdTe single-sideband electro-optic modulator working at 10.6 microm by
      dividing the modulator into two sections and driving each separately.

PMID- 19771029
TI  - Optical synthetic-aperture radar processor architecture with quadratic phase
      error correction.
AB  - Uncompensated phase errors limit the image quality of synthetic-aperture radar.
      We present an acousto-optic synthetic-aperture radar processor architecture
      capable of measuring the quadratic phase error. This architecture allows for the
      error signal to be fed back to the processor to generate the corrected image.

PMID- 19771028
TI  - Simple electronic speckle-shearing-pattern interferometer.
AB  - A simple electronic speckle-shearing-pattern interferometer, in which the image
      of an object is focused and sheared with a split lens onto a diffuser, is
      described. The sheared images on the diffuser are focused by a television camera
      and then digitized and processed in a host computer. The results obtained for two
      basic types of shearing, lateral and radial, are presented.

PMID- 19771030
TI  - Proposed Fraunhofer-wavelength atomic filter at 534.9 nm.
AB  - A new atomic filter is proposed. It operates at 534.9 nm. The new filter offers
      two important advantages for openchannel laser communications. First, its
      wavelength matches the output of the frequency-doubled Nd:BEL laser. Second, the
      filter overlays a solar Fraunhofer line, thereby offering intrinsic sunlight
      suppression. Ultranarrowband optical filtering takes place within the singlet
      manifold of neutral-calcium vapor. Excellent filter properties are deduced from
      spectroscopic examination of the atomic system. A novel feature of the new filter
      is the potential for greater-than-unity internal photon conversion.

PMID- 19771031
TI  - Resolution limit for anisotropic Bragg diffraction from finite holographic
      gratings.
AB  - Resolution limits resulting from Bragg diffraction from finite phase gratings are
      derived. The diffraction pattern is calculated as a sum of coherent waves
      diffracted from the gratings representing the Fourier transform of the finite
      grating. A photorefractive spatial light modulator has been built up that can
      resolve more than 30 line pairs per millimeter, comparable with the limiting
      value of 36 line pairs per millimeter derived by the theoretical treatment.

PMID- 19771032
TI  - Nonlinear Mie scattering: electrostrictive coupling of light to droplet acoustic
      modes.
AB  - Nonlinear Mie scattering at 532 nm was observed from 23-microm-diameter ethanol
      droplets excited by picosecond light pulses. Low-order optical modes (l = 2-4),
      normally hidden at low intensity, became visible as new peaks in elastic
      scattering spectra at 2 GW/cm(2). When higher-Q resonances were selectively
      excited, the scattered light showed an amplitude-modulated time dependence. The
      data are explained by electrostrictive generation of acoustic modes of the
      droplet by the incident radiation and subsequent coupling of the acoustic
      disturbance back onto the light field.

PMID- 19771033
TI  - Time-resolved transillumination for medical diagnostics.
AB  - A time-gated technique to improve the possibility of localizing spatial
      differences in absorption when transilluminating a turbid, highly scattering
      medium, such as human tissue, is demonstrated. When transmitting picosecond laser
      pulses and detecting photons on the opposite side of the object, the contrast can
      be strongly enhanced by detecting only the photons with the shortest traveling
      time. Measurements on a 35-mm-thick tissue phantom with 5-mm-diameter absorbing
      objects inside are reported with data for a human hand in vivo. Implications for
      optical mammography (diaphanography) are discussed.

PMID- 19771034
TI  - Hybrid acousto-optic and digital equalization for microwave digital radio
      channels.
AB  - Digital radio transmission systems use complex modulation schemes that require
      powerful signal-processing techniques to correct channel distortions and to
      minimize bit error rates. We propose combining the computation power of acousto
      optic processing and the accuracy of digital processing to produce a hybrid
      channel equalizer that exceeds the performance of digital equalization alone.
      Analysis shows that a hybrid equalizer for 256-level quadrature amplitude
      modulation (QAM) performs better than a digital equalizer for 64-level QAM.

PMID- 19771035
TI  - Enhanced-nonlinearity single-mode lead silicate optical fiber.
AB  - A single-mode lead silicate optical fiber has been fabricated to permit lower
      power all-optical switching. The core glass has a nonlinear index of refraction
      eight times that of silica. The loss of the fiber is less than 2 dB/m. Over 177pi
      of phase shift was obtained, as measured by self-phase modulation, in a 29-cm
      length of fiber. At the 1-kW peak power level required to produce this large
      phase shift, two-photon absorption and stimulated Raman scattering did not
      significantly degrade the desired nonlinear behavior.

PMID- 19771036
TI  - Simultaneous wave-front and polarization conjugation of picosecond optical pulses
      by stimulated Rayleigh-wing scattering.
AB  - Using phase conjugation by stimulated Rayleigh-wing scattering (SRWS) in carbon
      disulfide, we have observed simultaneous correction of wave-front and
      polarization distortions. SRWS was excited by pulses of 20-psec duration
      containing as much as 15 microJ of energy at a wavelength of 0.53 microm and
      produced phase-conjugate reflectivities as large as 10%.

PMID- 19771038
TI  - Origin of the sublinear photorefractive response time in BaTiO(3).
AB  - The sublinear dependence of the photorefractive grating formation time on laser
      intensity in BaTiO(3) is explained by the secondary-center photorefractive model.

PMID- 19771037
TI  - Stimulated Raman-scattering threshold behavior of binary mixture micrometer-sized
      droplets.
AB  - Stimulated Raman scattering (SRS) from binary liquid mixture micrometer-sized
      droplets irradiated by nanosecond laser pulses exhibits previously unreported
      features. SRS emission at wavelength shifts corresponding to combination
      frequencies of the individual component Stokes shifts are observed in droplets
      but not in bulk mixtures. Furthermore, droplet SRS thresholds are determined by
      component refractive indices and concentrations, in contrast to bulk thresholds,
      for which self-focusing likely plays a dominant role.

PMID- 19771039
TI  - Photorefractive effect in GaP.
AB  - The photorefractive effect in undoped semi-insulating GaP was observed. GaP has a
      photorefractive sensitivity in the spectral region of 0.6 to 0.9 microm. The
      photorefractive center is the deep donor resulting from the P antisite defect. We
      measured the two-beam coupling gain coefficient and its time constant as
      functions of the grating period and the pumping intensity, using a 633-nm He-Ne
      laser. The maximum gain coefficient of 0.33 cm(-1) was obtained at a grating
      period of 1.1 microm. The time constant, which depends on the grating period, was
      3-20 msec at a pumping intensity of 30 mW/cm(2).

PMID- 19771040
TI  - Gaindistribution measurements along an ultralong erbiumdoped fiber amplifier
      using opticaltimedomain reflectometry.
AB  - Optical gain changes as a function of distance along a long distributed erbium
      doped fiber amplifier were measured, using optical-time-domain reflectometry. Two
      dispersion-shifted erbium-doped fibers with fiber lengths of 9-19 km and doping
      concentrations of 0.5 (0.5 x 10(-4) wt %) and 0.1 (0.1 x 10(-4) Wt %) parts in
      10(6) have been tested, using 1.48-microm InGaAsP laser diode and 0.98-microm
      Ti:sapphire laser pump sources. It is shown how local gain and loss change with
      an increase in pump power.

PMID- 19771041
TI  - Experimental study of soliton transmission over more than 10,000 km in
      dispersiondaggershifted fiber.
AB  - Transmission of 50-psec solitons in a 75-km recirculating loop of dispersion
      shifted fiber (D = 1.38 psec/nm/km at lambda(s)), using low-gain erbium
      amplifiers spaced 25 km apart, displays jitter in pulse arrival times consistent
      with low error rates for transmission over 9000 km and for bit rates ?4
      Gbits/sec. Furthermore, a study of soliton pair propagation in the same loop
      shows no significant interaction over 9000 km for pair spacings >/=5tau.

PMID- 19771042
TI  - Inverse ion-exchange method for glass waveguide fabrication.
AB  - A new method, inverse ion exchange, is proposed and demonstrated for the
      fabrication of single-mode channel waveguides. In this method the channel
      waveguide is formed by backdiffusion of the refractive-index-increasing ions from
      an ion-exchanged planar waveguide. Finite-difference methods are used to model
      the fabrication technique and to calculate the field of the fundamental mode of
      the waveguide. It is also proved experimentally that single-mode waveguides can
      be fabricated with the the reinverse ion-exchange method using a 10-microm mask
      stripe width.

PMID- 19771043
TI  - Proposal for a magnesium photoionization laser at 24.7 nm.
AB  - A system is proposed in which resonantly excited Mg atoms are rapidly
      photoionized by soft x rays from a laserproduced plasma, causing inversion and
      superfluorescent laser action at 24.7 nm in Mg II. Calculations show that
      significant gains should occur when a moderately sized (10-J, 200-psec) 1064-nm
      pump laser is used.

PMID- 19771044
TI  - Efficient amplification of a single-mode laser diode by photorefractive beam
      combination using an injection-locked diode-laser array pump.
AB  - Powers in excess of 100 mW have been obtained in a near-diffraction-limited,
      single-mode laser-diode output by photorefractive two-beam coupling in BaTiO(3),
      using an injection-locked 1-W diode-laser array as the pump source. Signal gains
      of as much as 8.1 are obtained, corresponding to pump transfer efficiencies of
      49%. Calculations suggest that powers as high as 225 mW should be obtainable,
      given suitably antireflection-coated optics.

PMID- 19771045
TI  - Modes of a two-dimensional phase-locked array of vertical-cavity surface-emitting
      lasers.
AB  - A simple formalism is reported for studying the modes of an infinite two
      dimensional (2-D) phase-locked array of vertical-cavity surface-emitting diode
      lasers. In this approach, the Helmholtz equation is approximately separated into
      products of solutions of the associated one-dimensional (linear) arrays. This
      formalism allows the knowledge gained from years of research into the modal
      properties of linear diode arrays to be applied directly to 2-D arrays. As a
      result, it is expected that both 2-D gain-guided and index-guided arrays (except
      those with excess gain in the low-index channels) will lase in the high-order
      mode characterized by emission into four distinct off-axis far-field lobes. In
      contrast, it is expected that properly constructed 2-D leaky-mode arrays would
      lase preferentially in the fundamental mode well above threshold.

PMID- 19771046
TI  - Optical pattern recognition of letters by a joint-transform correlator using a
      ferroelectric liquid-crystal spatial light modulator.
AB  - The use of a joint-transform correlator (JTC) as an optical pattern-recognition
      system for letters has been studied. The system incorporates a ferroelectric
      liquid-crystal spatial light modulator (LAPS-SLM). The LAPS-SLM has a high
      contrast ratio and a fast response time, permitting the JTC to recognize more
      reference letters simultaneously than a classical correlator can.

PMID- 19771047
TI  - Particle-size distribution determination using optical sensing and neural
      networks.
AB  - We present an inverse technique to determine particle-size distributions by
      training a layered perception neural network with optical backscattering
      measurements at three wavelengths. An advantage of this approach is that, even
      though the training may take a long time, once the neural network is trained the
      inverse problem of obtaining size distributions can be solved speedily and
      efficiently.

PMID- 19771048
TI  - Complex reference-invariant joint-transform correlator.
AB  - The joint-transform correlator operation has been extended to include complex
      reference images. Such amplitude and phase images are common when single harmonic
      images (circular, radial, logarithmic, etc.) are used in correlation setups. The
      analysis of a rotation-invariant pattern-recognition system using joint-transform
      correlator principles is described, followed by experimental results that can be
      obtained in real time.

PMID- 19771049
TI  - Character recognition using a dynamic optoelectronic neural network with unipolar
      binary weights.
AB  - A novel type of quantized learning rule with unipolar binary weights that is
      useful for the optical implementation of neural networks is reported. An input
      dependent thresholding operation is also proposed to remove the unwanted effects
      that are due to the insufficient contrast ratio of spatial light modulators as
      synaptic connection devices. Moreover, we experimentally demonstrate the
      recognition of 26 characters of the alphabet by using the single set of an
      optoelectronic three-layered network.

PMID- 19771050
TI  - Feasibility of nonlinear reflection of light by a collisionless molecular beam.
AB  - Numerical solutions of the Maxwell-Bloch equations describing the nonlinear
      absorption of an IR laser field as it propagates across a collisionless molecular
      beam are presented. Calculations show the possibility that the laser field
      experiences a self-reflection inside the molecular beam while it is being
      absorbed. Since the density of the molecular beam changes smoothly in the radial
      direction, there are no reflections induced by its boundaries, and it constitutes
      an ideal system to study the self-reflected wave. The reflectivity of the
      molecular beam is predicted to be vanishingly small at low intensities but to
      increase dramatically as the nonlinear effects become significant.

PMID- 19771051
TI  - Dispersion effects in four-wave mixing measurements of ions in solids.
AB  - We have performed nondegenerate four-wave mixing measurements on Cr(3+) ions in
      three crystals: BeAl(2)O(4), Gd(3)Sc(2)Ga(3)O(12), and LaMgAl(11)O(19). Two laser
      beams of the same frequency were used to resonantly pump one of the absorption
      bands of Cr(3+), and probe beams with three different wavelengths ranging from
      442 to 1064 nm were used to generate a signal from the laser-induced population
      grating. The observed four-wave mixing signal strength was found to increase as
      the wavelength of the probe beam was decreased. A model was utilized to explain
      these results based on the change in polarizability of the Cr(3+) ions when they
      are in the metastable state versus the ground state, and it was found that the
      dispersion effects can be described by a single-oscillator model with the lowest
      energy charge-transfer transition of Cr(3+) making the dominant contribution to
      the signal.

PMID- 19771052
TI  - Second-order polarizability holograms in few-mode fibers: phase conjugation and
      angular selectivity.
AB  - Second-order polarizability holograms in optical fibers were recorded by
      picosecond radiation of a neodymium laser together with its second harmonic. High
      angular selectivity of holograms was observed for various input angles of the
      reading IR beam. We observed phase conjugation of the green signal by using an
      oppositely directly IR beam to read the holograms. Coherent erasure of a hologram
      was demonstrated by means of a second exposure by an interference pattern of
      opposite sign.

PMID- 19771053
TI  - Measuring vibration amplitudes in the picometer range using moving light gratings
      in photoconductive GaAs:Cr.
AB  - We report the measurements of picometer vibration amplitudes produced by a piezo
      mirror in an interferometric setup, using a GaAs:Cr photoconductive device. The
      moving light fringes (gratings) induce in this new detector periodic
      photocurrents characterized by efficient suppression of the low-frequency drifts
      of the working point and low sensitivity to the amplitude laser noise. The
      optimum operation conditions of this system are also shown.

PMID- 19771054
TI  - Embedded fiber-optic sensor utilizing the modal power distribution technique.
AB  - The modal power distribution technique is applied to a multimode optical fiber
      embedded in a three-dimensional composite material for real-time characterization
      and monitoring of the structure. The measurements on the modal power distribution
      within these fibers, and the subsequent redistribution induced by external
      perturbation, indicate that the modal power distribution technique is more
      sensitive than the intensity-modulation technique for smart-structure
      characterization.

PMID- 19771055
TI  - Three-dimensional acousto-optic spectrum analysis.
AB  - A three-dimensional acousto-optic spectrum analyzer with subhertz resolution is
      demonstrated experimentally. The first and second dimensions are the two spatial
      dimensions of the output detector array, and the third dimension is time as
      sampled by the detector array frame rate. A superfine resolution of 0.12 Hz has
      been achieved.

PMID- 19771056
TI  - Adaptive fringe-locked running hologram in photorefractive crystals: errata.

PMID- 19771057
TI  - Fiber-optic interferometric sensor for the detection of acoustic emission within
      composite materials.
AB  - An optical-fiber Michelson interferometric acoustic emission sensor is described.
      The sensor uses ordinary singlemode fiber and is embedded in the composite
      material under test. Signals are demodulated through the active homodyne. This
      system provides a novel approach for material nondestructive evaluation.

PMID- 19771058
TI  - Focal curves generated by one-dimensional gradient-index tapers.
AB  - A preliminary study on focal curves generated by one-dimensional gradient-index
      tapers is presented. An asymptotic wave method is applied to derive the optical
      propagator and to solve propagation in these inhomogeneous media.

PMID- 19771059
TI  - Light transmission from a randomly rough dielectric diffuser: theoretical and
      experimental results.
AB  - We report numerical and experimental observations of a new transmission effect in
      rough dielectric interfaces.

PMID- 19771060
TI  - Diffraction efficiency gain, blazing, and apodizing of a symmetric square
      reflection grating in an etalon.
AB  - First-order diffraction efficiency of 50% into a single beam was obtained from a
      weak symmetric square metal diffraction grating operated in an etalon at the
      632.8-nm He-Ne laser wavelength. Without the etalon the diffraction efficiency
      was just 2.7% in each of the two first-order beams. First-order diffraction
      efficiency gain as well as blazing and apodizing of the grating occur because of
      the resonant paraxial angular spectrum of the etalon.

PMID- 19771061
TI  - Effect of signal frequency on four-wave mixing through stimulated Brillouin
      scattering.
AB  - We present measurements of the dependence of the phase-conjugate reflectivity on
      signal frequency for Brillouinenhanced four-wave mixing at pump intensities above
      the threshold instability. The measurements were made in TiC1(4) at lambda = 1
      microm and are consistent with a computer model of the reflectivity. We have
      observed that the frequency of the conjugate beam is independent of the frequency
      of the input signal beam in the unstable regime.

PMID- 19771062
TI  - Phase conjugation by degenerate four-wave mixing in barium vapor.
AB  - We report what is to our knowledge the first observation of phase-conjugate waves
      by degenerate four-wave mixing in Ba vapor near its 6s(2)(1)S(0) ? 6s6p(1)P(1)
      resonance transition. A maximum reflectivity of 36% at 10 mbars of Ar buffer gas
      pressure is observed together with a temporal pulse shortening of 50%. Conical
      emission in the two pump waves after their passage through the nonlinear medium
      is also observed. The dependence of the phase-conjugate signal on the pressure of
      the Ar buffer gas shows a small state-changing collisional decay rate.

PMID- 19771063
TI  - Perturbation-induced dynamics of small-amplitude dark optical solitons.
AB  - It is demonstrated that the dynamics of small-amplitude dark solitons in optical
      fibers may be described by the wellknown Korteweg-de Vries equation. This
      approach allows us to explain analytically the temporal self-shift of dark
      solitons due to the Raman contribution to the nonlinear refractive index, which
      has been observed experimentally by Weiner et al. [Opt. Lett. 14, 868 (1989)].

PMID- 19771064
TI  - Phase measurement for surface infrared-visible sum-frequency generation.
AB  - We present what are to our knowledge the first measurements of the phase of the
      infrared-visible sum-frequency generation signal. We introduce two techniques and
      apply the measurements to the determination of the polar orientation of a
      selected group of atoms within an adsorbed molecule.

PMID- 19771065
TI  - Efficient self-pumped phase conjugation at near-infrared wavelengths using cobalt
      doped BaTiO(3).
AB  - Using BaTiO(3) crystals doped with cobalt, we have measured the reflectivity of
      self-pumped phase-conjugate mirrors operating in the total-internal-reflection
      geometry as a function of wavelength in the range between 633 and 933 nm. We find
      that for cobalt concentrations above 25 parts in 10(6), the reflectivity is
      higher than 50% for all the investigated wavelengths. At a wavelength of 800 nm
      the reflectivity is independent of incident power over a range of 12 to 600 mW.

PMID- 19771066
TI  - Collapse of optical pulses.
AB  - Under the combined effect of diffraction, anomalous dispersion, and nonlinear
      refraction, an optical pulse can collapse simultaneously in time and space. Such
      a collapse could yield short pulses with extremely large optical fields. Light
      bullets-pulses that propagate without change in space or time-are also possible.
      The condition for such a collapse and possible experiments are discussed.

PMID- 19771067
TI  - Self-amplitude modulation in the vicinity of the zero-dispersion point in phase
      shift-keying coherent optical transmission systems.
AB  - A simple approximate analytical expression is derived for the intensity
      modulation index in a phase-shift-keying coherent optical transmission system,
      accounting for both group-velocity dispersion and higher-order dispersion. This
      provides an analytical generalization of previously presented numerical results
      obtained in the limits of pure group-velocity dispersion and higher-order
      dispersion, respectively. The subsequently derived maximum transmission distance
      for 50% intensity modulation is found to be long at the zero-dispersion
      wavelength. However, for high modulation frequencies, the maximum transmission
      distance decreases rapidly when the wavelength deviates from the zero-dispersion
      wavelength. Comparisons with previously obtained numerical solutions show good
      agreement.

PMID- 19771068
TI  - Polarization discrimination properties of Bragg-reflection waveguides.
AB  - Finite-clad Bragg-reflection waveguides are analyzed by a leaky-wave approach.
      The eigenvalue equation for TE and TM propagation is derived, and approximate
      expressions are given for the loss coefficient. Proper design of these structures
      is shown to lead to high polarization discrimination.

PMID- 19771070
TI  - Pulse shaping, compression, and pedestal suppression employing a nonlinear
      optical loop mirror.
AB  - We study the shaping of picosecond-duration optical pulses by the intensity
      dependent transmission characteristics of a fiber loop mirror in the normally
      dispersive region. Experimental results for sech(2) intensity input profiles are
      in good agreement with the theoretical predictions. In addition, input pulses
      with substantial background radiation emerge both compressed and pedestal free.

PMID- 19771069
TI  - Simple extension to the Fabry-Perot technique for accurate measurement of losses
      in semiconductor waveguides.
AB  - A simple modification to the Fabry-Perot technique for the measurement of
      semiconductor waveguide losses is described. The modification dispenses with the
      need for knowing implicitly the reflectivities of end faces of the waveguide,
      which are usually difficult to ascertain experimentally.

PMID- 19771071
TI  - Buildup of steady-state subpicosecond and femtosecond pulses in a colliding-pulse
      mode-locked ring dye laser.
AB  - We show for the first time, to our knowledge, that the buildup time to steady
      state femtosecond pulses in a typical colliding-pulse mode-locked dye laser
      (lambda = 620 nm) with compensating prisms is 15 microsec after the pulses have
      been completely modulated. For a similar laser without the compensating prisms,
      the buildup time is 40 microsec and exhibits interesting oscillatory behavior in
      the initial stage.

PMID- 19771072
TI  - Starting dynamics of additive-pulse mode locking in the Ti:A1(2)O(3) laser.
AB  - The starting dynamics of the additive-pulse mode-locked Ti:AI(2)O(3) laser are
      investigated. Mode locking develops from mode beating with pulse formation times
      of several hundred microseconds. A simple model based on additivepulse mode
      locking theory is developed that describes self-starting and pulse evolution.

PMID- 19771073
TI  - Additive-pulse mode locking of a diode-pumped Nd:YLF laser.
AB  - We investigate the passive self-starting technique of additive-pulse mode locking
      of a diode-laser-pumped Nd:YLF laser. Pulses of 1.5-psec duration at a repetition
      rate of 123 MHz have been obtained, using only a single-mode optical fiber in an
      external feedback cavity to achieve pulse formation. The sech(2) pulses are
      approximately transform limited and to our knowledge the shortest that have been
      produced by a Nd:YLF laser. The laser was pumped by two 1-W laser-diode arrays
      and had usable output power of 20 mW, corresponding to a peak power of 108 W.

PMID- 19771074
TI  - Self-stabilization of synchronously mode-locked lasers.
AB  - An empty and highly attenuating external cavity was recently shown to have a
      powerful stabilizing influence on a synchronously mode-locked laser. Numerical
      simulations presented here demonstrate how this stabilization technique works.
      For an external cavity marginally shorter than the main cavity, the extremely
      weak reinjected signal isolates the mode-locked pulse from the noise background,
      which otherwise causes jitter. The new technique is likely to be of considerable
      importance for researchers using this popular type of mode-locked laser.

PMID- 19771075
TI  - Image synthesis from wave-front sensor measurements of a coherent diffraction
      field.
AB  - We demonstrate that images of laser-illuminated objects can be formed from
      measurements of the wave-front slope (gradient) associated with the
      backscattered, coherent laser-speckle field. A digital wave-front recovery and
      image synthesis procedure is described, and the results of computer-simulation
      experiments are presented in which coherent images are reconstructed from
      digitally simulated Fourier-plane laser-speckle measurements. Images are
      recovered from noisy wave-front-difference data to illustrate the effect that
      measurement noise has on recovered image quality.

PMID- 19771076
TI  - Optical polynominal processing based on a cascaded holographic structure.
AB  - An optical polynomial processor is investigated to evaluate a general class of
      nonlinear functions. The polynomial processor is based on a cascaded holographic
      array that is reconstructed by an off-Bragg laser beam. By means of cascaded off
      Bragg reconstructions, a series of polynomial terms can be obtained in parallel
      at light-transmitted speed.

PMID- 19771077
TI  - Polarization diversity detection for fiber interferometers using active feedback
      control of output polarization-mode selection.
AB  - The application of an adaptive polarization diversity detection technique in an
      interferometric fiber sensor system is described. The approach utilizes feedback
      control of the polarization modes selected at the sensor output and produces the
      optimum level of total interference signal while allowing the states of
      polarization of the light in the signal and reference arms of the interferometer
      to vary randomly.

PMID- 19771078
TI  - Moire signals by the photoacoustic effect.
AB  - We report the detection of moire displacement signals using the photoacoustic
      effect. By using the transmission and reflection (absorption) gratings with a
      25microm pitch, the lateral displacement of the grating is detected from the
      photoacoustic signals. The probe-beam deflecton method and the microphone method
      are used for detecting the acoustic vibration and the acoustic pressure,
      respectively. The signals vary periodically as the pitch of the grating for the
      lateral displacement. The characteristics of the displacement signal are also
      examined by using the Fresnel diffraction theory.

PMID- 19771079
TI  - Stable fiber-source gyroscopes.
AB  - We describe two new configurations of fiber gyroscopes that use superfluorescent
      fiber laser sources. In the first configuration we introduce a backward-pumping
      technique that achieves an order-of-magnitude increase in the power that can be
      launched into the gyroscope without instabilities. In the second configuration we
      employ the optical gain of the superfluorescent fiber laser source to amplify the
      signal returned from the gyroscope, obtaining an additional three-orders-of
      magnitude increase in the optical power incident upon the detector, with an
      implication for simplification of the electronics. In both configurations, source
      beat-noise-limited rotation sensitivity is achieved.

PMID- 19771081
TI  - Image production due to backscattering.
AB  - The observation of an image produced by enhanced multiple backscattering is
      reported. Light is focused through a 25-microm pinhole and permitted to fall upon
      a scattering screen consisting of a suspension of polystyrene spheres. The
      backscattered light is found to produce an image of the source. Preliminary
      results on the image of a two-slit source are also presented.

PMID- 19771080
TI  - Formulation of stellar speckle interferometry in terms of joint spatial/spatial
      frequency representations.
AB  - We propose a generalized formulation of stellar speckle interferometry (SSI) and
      related techniques in terms of joint spatial/spatial-frequency energy
      representations. We show how, within this formulation, techniques such as that of
      Knox-Thompson, or even standard SSI, appear to be particular implementations of a
      more general method. This generalized SSI is derived in a straightforward manner
      from the proposed joint formulation. Results from a computer simulation are
      presented.

PMID- 19771082
TI  - Grating axicon for collimating Cerenkov radiation waves.
AB  - An axicon optical element that utilizes a diffraction grating has been fabricated
      for collimating the Cerenkov radiation wave. The grating axicon has the advantage
      of a simple structure, which can easily be fabricated by the computerized
      numerical control machining technique. The collimation function of the grating
      axicon is confirmed for Cerenkov-type second-harmonic generation in LiNbO(3)
      waveguides, and correction of the aberration caused by substrate anisotropy is
      investigated. The aberration can be compensated by appropriately inclining either
      the substrate facet or the grating axicon.

PMID- 19771083
TI  - Room-temperature 1.06-0.53-microm second-harmonic generation with MgO:LiNbO(3).
AB  - Room-temperature 1.06-0.53-microm second-harmonic generation (SHG) achieved with
      LiNbO(3) doped with 7 mol. % MgO has been studied. Phase matching was achieved
      with angle tuning. SHG conversion efficiency of 45% was obtained with a 12-mm
      long crystal and a fundamental peak-power density of 140 MW/cm (2). SHG
      performance of MgO:LiNbO(3) is compared with that of KTP and LBO crystals.
      Various phase-matching parameters of MgO:LiNbO(3) were calculated as functions of
      the fundamental wavelength, using the experimentally determined Sellmeier
      equations. It was found that room-temperature, noncritically-phase-matched Type I
      SHG can be achieved in this crystal at 1.053 microm, where Nd:YLF lasers operate.

PMID- 19771084
TI  - Spatial-mode cleanup of a pulsed laser beam through mutually pumped phase
      conjugation with a cw reference.
AB  - A method of cleaning up the spatial mode of a pulsed laser beam without using a
      pinhole is proposed and demonstrated. The method consists of performing mutually
      pumped phase conjugation (MPPC) between the pulsed laser beam and a cw reference,
      thereby transferring the desirable spatial mode of the cw beam onto the pulsed
      beam. In these experiments MPPC is observed in a photorefractive BaTiO(3) crystal
      between the beams from a Q-switched flash-lamp-pumped Nd:YAG laser and a diode
      pumped cw Nd:YAG laser, both operating at 532 nm. The experimental results showed
      convincing spatial-mode cleanup of the pulsed beam, with an approximately 3%
      conversion efficiency. A method of significantly increasing the overall
      efficiency is discussed. To the author's knowledge, this is the first reported
      MPPC between pulsed and cw laser beams.

PMID- 19771085
TI  - Accumulation of Raman gain between closely spaced pulse pairs.
AB  - The short-pulse conversion efficiency of stimulated Raman scattering in Pb vapor
      is increased from 15% to 35% by using a novel technique that employs a closely
      spaced pair of pump pulses. The second pulse scatters off the coherent excitation
      induced in the medium by the first pulse, with a resultant enhancement in
      efficiency. To our knowledge these results give the first observation of such
      long-lived cooperative phenomena in stimulated Raman scattering. We have also
      observed this phenomenon in H(2) and show that this technique is readily
      applicable to other Raman-active media.

PMID- 19771086
TI  - Coherent amplification of ultrashort solitons in doped fibers.
AB  - We present the results of computer simulation of coherent amplification of
      solitons in doped fibers and explain the first stage of an evolution of such
      solitons by means of a perturbation theory applied to the inverse scattering
      problem in two limiting cases, noncoherent and pure coherent amplification. We
      show that it is possible to get adiabatic amplification of solitons. In the case
      of noncoherent amplification the amplitude of the solitons increases
      exponentially and the pulse duration decreases exponentially. In the opposite
      case of pure coherent amplification the amplitude of the solitons increases
      linearly with distance z, whereas the pulse duration displays a z(-1) dependence.

PMID- 19771087
TI  - Phase noise in photonic communications systems using linear amplifiers.
AB  - Spontaneous emission noise limits the capacity and range of photonic
      communications systems that use linear optical amplifiers. We consider here the
      question of phase detection in such systems. Amplitude-to-phase-noise conversion
      occurs owing to the nonlinear Kerr effect in the transmission fiber, resulting in
      optimal phase noise performance when the nonlinear phase shift of the system is
      approximately 1 rad. Error-free state-of-the-art systems that use phase detection
      at multigigabit rates are thereby limited to a range of a few thousand
      kilometers.

PMID- 19771088
TI  - Optical characterization of arsenic-doped silica-on-silicon waveguides using
      femtosecond optical-time-domain-reflectometry techniques.
AB  - Femtosecond OTDR diagnostic techniques are used to investigate the optical
      properties of arsenic-doped silica-onsilicon waveguides. Results demonstrate that
      these waveguides have a relatively high refractive index (1.51) and a low loss
      (<0.5 dB/cm). Owing to the tight optical confinement of the guides, they will
      have important applications in areas in which high packing densities are required
      or where direct coupling from semiconductor lasers is needed.

PMID- 19771089
TI  - Off-axis prism resonator for improved beam quality of slab lasers.
AB  - An off-axis prism resonator that was especially designed for slab lasers is
      investigated. It consists of an output coupling mirror and two 90-deg prisms, one
      of which is placed off axis. This arrangement permits a fill factor of one and
      reduces the mode order of the extracted beam compared with that of a conventional
      stable mirror resonator. Thus a high extraction efficiency and high beam quality
      are achieved.

PMID- 19771090
TI  - Self-quenching of fundamental phase and amplitude noise in semiconductor lasers
      with dispersive loss.
AB  - We show theoretically that the incorporation of a frequency-dependent loss
      mechanism in a semiconductor laser can lead, in concert with the amplitude-to
      phase coupling, to major reductions of the fundamental intensity and phase noise.
      A loss dispersion of the wrong sign, on the other hand, leads to an increase of
      the noise and, at a certain strength, to instability.

PMID- 19771091
TI  - Optical neurochip based on a three-layered feed-forward model.
AB  - We report on a GaAs/AlGaAs optical neurochip based on a three-layered feed
      forward model. The optical neurochip consists of a light-emitting diode array
      with 66 elements, a fixed interconnection matrix, and a photodiode array with 110
      elements. The interconnection matrix is determined by the backpropagation
      learning rule with three quantized levels. There are 35, 29, and 26 neurons,
      respectively, in the input, hidden, and output layers. The excitatory and
      inhibitory synapses are integrated on one chip. By using the chip and external
      electronics, we have succeeded in the recognition of 10 characters with 5 x 7
      bits.

PMID- 19771092
TI  - Generation of a high-repetition-rate train of practically noninteracting solitons
      by using the induced modulational instability and Raman self-scattering effects.
AB  - A new method for high-repetition-rate (approximately terahertz) soliton train
      generation in optical fibers from a cw signal is suggested. The method permits
      the conversion of all the signal energy into the soliton train energy without the
      appearance of a pedestal.

PMID- 19771093
TI  - Generation of tunable femtosecond pulses in a traveling-wave amplifier.
AB  - Time-resolved amplification of a chirped white-light continuum in a traveling
      wave amplifier is utilized for generation of pulses with durations of the order
      of 100 fsec that are continuously tunable between 660 and 740 nm.

PMID- 19771094
TI  - Generation of subpicosecond high-power optical pulses from a hybrid mode-locked
      semiconductor laser.
AB  - Ultrashort optical pulses 0.46 psec in duration with over 70 W of peak power are
      generated from an all-semiconductor laser-diode system. These results represent
      to our knowledge both the shortest and most-intense optical pulses generated from
      an all-semiconductor laser system.

PMID- 19771095
TI  - Pulse propagation near zero group-velocity dispersion in a femtosecond dye laser.
AB  - The propagation of femtosecond pulses in a colliding-pulse mode-locked dye laser
      near zero group-velocity dispersion is studied. The pulse spectrum is shown to
      exhibit a double-peak structure. This structure and its dependence on the
      intracavity dispersion can be explained by nonlinear pulse propagation near zero
      dispersion. A value for the third-order dispersion of the laser cavity is deduced
      and is found to be predominant for pulses shorter than 50 fsec.

PMID- 19771096
TI  - Coupled-cavity resonant passive mode-locked Ti:sapphire laser.
AB  - We use a nonlinear quantum-well reflective sample in a coupled-cavity
      configuration for resonant passive mode locking of a Ti:sapphire laser, producing
      tunable pulses as short as 2 psec. Pulses of less than 10-psec duration are
      observed over a 50-nm wavelength tuning range using a single-quantum-well
      reflector, over approximately 2 mm of external cavity length detuning. Stable
      mode-locked pulse trains are obtained without active cavity length control;
      however, the optical spectrum depends on the phase. We generate up to the sixth
      harmonic of the fundamental repetition rate, at 1.2 GHz, by simply decreasing the
      external cavity length.

PMID- 19771097
TI  - Modified shift-and-add speckle imaging algorithm.
AB  - A simple but powerful improvement of the shift-and-add method for the restoration
      of astronomical images is presented. In this modified algorithm, the shift vector
      and weight of a specklegram are estimated by computing the cross correlation
      between the specklegram and the current average before shifting the specklegram
      and updating the average. In this sense, all the information contained in the
      specklegrams is used for maximizing the coherence during the averaging process.
      Numerical simulations indicate that the suggested modification widens the
      applicability of the shift-and-add method to extended objects without the
      appearance of ghost images.

PMID- 19771098
TI  - Nonlinear image processing by a rotating kernel transformation.
AB  - We present a new method for nonlinear image processing that is well suited for
      hybrid optical-electronic implementation. An input image is convolved with a
      long, narrow two-dimensional kernel that is rotated, either continuously or
      discretely, through 360 deg. During rotation the convolution output is monitored,
      and the maximum and minimum values measured at each point are stored. The
      processed image is given by an application-dependent function of Max(x, y) and
      Min(x, y). Setting the output equal to [Max(x, y) - Min(x, y)] enhances straight
      line features in noisy, low-contrast images. Better results can be obtained by
      cascading a Max and a [Max - Min] operation. Numerically calculated examples
      illustrate the method and compare it with linear filtering.

PMID- 19771099
TI  - General criteria for nonclassical photon statistics in multimode radiations.
AB  - Using Muirhead's inequality based on the concept of majorization, general
      criteria for nonclassical photon statistics of arbitrary orders and involving any
      number of modes of radiations are derived. For the case of second-order
      correlations, it implies that both intramode antibunching and intermode bunching
      can contribute toward making multimode radiations nonclassical.

PMID- 19771100
TI  - Optical implementation of a quadratic associative memory by using the
      polarization-encoding process.
AB  - As a higher-order associative memory of a neural network, the quadratic
      associative memory is implemented holographically by using the polarization
      encoding process. The use of polarization encoding to represent sign in the
      quadratic associative memory tensor is made by twisted nematic liquid-crystal
      light modulators. Experimental results of retrieving the stored objects from an
      incomplete input are presented.

PMID- 19771101
TI  - Random-dot hologram.
AB  - In an attempt to make an easily viewable and self-contained test for stereopsis,
      a white-light reflection hologram was made of a Juleszian random-dot stereogram.
      The resulting hologram was free of monocular cues.

PMID- 19771102
TI  - Interferometric measurement of fiber strain hysteresis and nonlinearity for
      sensitivity optimization.
AB  - A simple and reliable fringe-counting method is used to determine the fiber
      static elastic response in fiber-optic sensors and modulators. Large strain
      hysteresis and nonlinearity have been observed in the commonly employed
      configuration of bonding a bare fiber onto a strain element. Jacketed fibers show
      reduced hysteresis and nonlinearity in their elastic response. Reductions in
      hysteresis from 23% to 1% of the maximum strain and in the nonlinearity by a
      factor of 3 have been measured.

PMID- 19771103
TI  - Velocity measurement using the phase shift of a laser-induced grating.
AB  - We have developed a simple and general technique for measuring the flow velocity
      over a wide range of values. It involves creating a cw light-induced grating and
      measuring the velocity-induced phase shift occurring in a known time period. It
      uses polarization spectroscopy and optical heterodyne detection with two beams
      from a single cw laser. Measurements are made of the two spatial phase components
      of the induced steady-state grating, and their ratio determines the velocity.
      Because a ratio is computed, the effects of many possible error sources cancel
      out. We have demonstrated this method for an approximately 1-m/sec flow of
      ethanol seeded with an absorbing, nonfluorescing dye.

PMID- 19771104
TI  - Focused laser intensity measurement at 10(18) W/cm(2) and 1053 nm.
AB  - We present a simple experimental setup that makes possible the measurement of the
      beam section at focus under full-power conditions. We demonstrate that a 1.5-TW
      laser system can be focused down to a 13.5-microm-diameter spot using
      conventional lens focalization, thus achieving laser intensities of up to 10(18)
      W/cm(2).

PMID- 19771105
TI  - Multiplex degenerate four-wave mixing in a flame.
AB  - The principle of multiplex degenerate four-wave mixing (DFWM) is demonstrated by
      recording, with a single laser shot, DFWM signals from both D lines of atomic
      sodium in a seeded flame. Applications of the technique for singleshot
      temperature measurements for combustion diagnostics are discussed.

PMID- 19771106
TI  - Development of single-mode four-fiber ribbon splicer with accurate splice loss
      estimation.
AB  - A mass-fusion splicer for single-mode four-fiber ribbon has been developed with
      an accurate splice loss estimation function capability. Measurements in two
      orthogonal directions are used to obtain a high axis offset resolution of 0.3
      microm. An average splice loss of 0.05 dB and an average splice loss estimation
      error of -0.002 dB are achieved.

PMID- 19771107
TI  - Maximum power of refractive lenses: a fundamental limit.
AB  - This paper explores the maximum optical power, i.e., the shortest focal length,
      that can be achieved with homogeneous materials given a cylindrical volume and a
      minimum-diameter constraint. An equation for the maximum optical power for a
      given lens diameter and two refractive indices is defined. For example, we
      determine that a 25.4-mm-diameter lens assembly cannot have an effective focal
      length of </=6 mm using existing optical glasses in the visible.

PMID- 19771108
TI  - Pitchfork bifurcation using a two-beam nonlinear Fabry-Perot interferometer: an
      analytical study.
AB  - A recent modal theory of nonlinear planar resonators is applied to the analysis
      of the steady transmission characteristics of the two-beam nonlinear Fabry-Perot
      interferometer. An analytical study, based on the planewave approximation, is
      presented that shows the potential applications of the device. In particular, a
      flip-flop mode of operation, derived from a pitchfork bifurcation, is predicted.
      Its salient feature is to require only positive triggering pulses.

PMID- 19771109
TI  - Ferroelectric liquid-crystal digital scanner.
AB  - The design and performance of a digital scanner based on ferroelectric liquid
      crystal switchable wave plates and passive nematic liquid-crystal prisms are
      reported. The liquid-crystal prisms function as low-cost, integrable, lowangle
      birefringent prisms. A 1 x 64 scanner was built with -5.3 dB of average loss. By
      using an active filter, the limiting mispolarization cross talk of the scanner
      was reduced from -13 dB to less than -25 dB.

PMID- 19771110
TI  - Stokes-vector reconstruction.
AB  - Light of arbitrary incident polarization that diffuses through a sufficiently
      thick multiply scattering medium emerges totally depolarized with a Stokes vector
      that is that of natural light. It is shown how to reconstruct the Stokes vector
      of the incident beam by making four speckle correlation measurements on the
      totally depolarized, diffusely scattered light. The theory is confirmed by
      experiment.

PMID- 19771111
TI  - Reflection from fractal multilayers.
AB  - The reflection and transmission properties of finely divided fractal layers are
      investigated and characterized. The results for electromagnetic or optical waves
      normally incident upon Cantor bar fractal layers are found for different stages
      of fractal growth. We develop a new exact self-similar algorithm that makes use
      of the self-similarity of these structures. This fractal computational scheme
      provides the reflection and transmission coefficients for hundreds or thousands,
      or more, of fractally distributed layers with extreme economy when compared with
      traditional approaches.

PMID- 19771112
TI  - Spectral measurement of the nonlinear refractive index in ZnSe using self-bending
      of a pulsed laser beam.
AB  - The nonlinear refractive-index (n(2)) spectrum of ZnSe near the band gap
      (lambda(gap) approximately 450 nm) at 77 K was measured for the first time to our
      knowledge by using self-bending of a pulsed laser beam. The maximum nonlinearity,
      n(2) approximately 1.9 x 10(-8) cm(2)/W, measured by us is anomalously large,
      which cannot be explained by conventional thermally induced band-gap shrinkage.

PMID- 19771113
TI  - Hydrostatic pressure effects on mode propagation in highly birefringent two-mode
      bow-tie fibers.
AB  - An experimental study on the effects of high hydrostatic pressure of as much as
      100 MPa on mode propagation in a highly birefringent two-mode bow-tie fiber is
      presented. Hydrostatic pressure is found to produce a large phase shift between
      both orthogonal polarizations in fundamental and second-order modes and also
      between the two lowest-order spatial modes in the highly birefringent two-mode
      bow-tie fiber. The pressure-induced effects are expressed in terms of
      birefringence changes and pressure phase sensitivity, both described by the
      experimental parameter T(p). The results indicate that pressure phase sensitivity
      between the two spatial modes, 1.3 rad/MPa-m, is approximately one order lower
      than for polarization modes.

PMID- 19771114
TI  - Optical homodyne detection with an injection-locked Er-doped-fiber ring laser.
AB  - Optical homodyne detection is demonstrated with an injection-locked Er-doped
      fiber ring laser. A 3-MHz phase-modulated optical signal is successfully
      demodulated.

PMID- 19771115
TI  - Asymmetric behavior of polished polarization-maintaining couplers.
AB  - Basic asymmetric behavior is experimentally observed in a polished polarization
      maintaining fiber coupler. As the two half-couplers are made to slide on top of
      each other, the output extinction ratio exhibits relatively large variations
      whose forms depend on the fiber that is selected for the input. We propose that a
      local distortion of the fiber birefringent axes, which could be caused by the
      half-coupler polishing process, can generate such features even when the launched
      light is perfectly polarized along a principal axis of the input fiber.

PMID- 19771116
TI  - Guiding-center soliton in optical fibers.
AB  - For a relatively long optical pulse in a fiber with a dispersion distance z(0)
      much larger than the loss distance, a soliton cannot exist in an ideal sense.
      However, with a proper choice of the initial amplitude and amplifier distance
      z(a), a nonlinear pulse (a guiding-center soliton) propagates like a soliton over
      a distance much larger than the dispersion distance when it is periodically
      amplified at distances much shorter than the dispersion distance. The
      guidingcenter soliton is shown to satisfy the nonlinear Schrodinger equation with
      a correction of order (z(a)/z(0))(2). Numerical examples supported by analytical
      results are presented for distortionless propagation of the guiding-center
      solitons with a pulse width of 40 psec in a dispersion-shifted fiber of D = 1
      psec/(nm-km).

PMID- 19771117
TI  - High-efficiency single-order waveguide grating coupler.
AB  - High-efficiency single-order grating coupling between an optical waveguided mode
      and a volume wave is achieved by means of a double-sided corrugated cover film
      that has phase-shifted undulations. A greater than 90% outcoupling ratio into air
      is demonstrated for weakly guiding ion-exchanged waveguides. The conditions for
      efficient coupling and the tolerances on them are established.

PMID- 19771118
TI  - Observation of tunable far-infrared emission from optically pumped D2O with a 17
      GHz tuning range.
AB  - We report the observation of tunable far-infrared emission from D(2)O with a 17
      GHz tuning range. Using a tunable high-pressure CO(2) laser for optical pumping,
      we have studied laser emission from D(2)O and achieved tunable laser emission
      from 91.23 to 91.81 cm(-1) with a maximum detuning of 13 GHz from resonance. We
      have also studied the temporal behavior of the far-infrared laser emission.

PMID- 19771119
TI  - High-power fast-axial-flow CO2 laser with a variable-reflectivity output coupler.
AB  - We report what is to our knowledge the first cw, dc-excited, fast-axial-flow
      CO(2) laser using a variable-reflectivity output coupler. A super-Gaussian
      reflectivity profile of order 8 with 96% central reflectivity has been achieved
      by depositing a low-absorption coating onto a ZnSe substrate. The unstable
      resonator oscillated in the lowest-order mode to produce a diffraction-limited
      beam of 300 W of power and 0.35-mrad divergence angle (FWHM). The measured near
      field and far field are in good agreement with the mathematical model. The
      technique lends itself to extrapolation to the kilowatt level.

PMID- 19771120
TI  - Stable semiconductor laser with a 7-Hz linewidth by an optical-electrical double
      feedback technique.
AB  - A semiconductor laser with a linewidth of 7 Hz locking to a supercavity was
      achieved by using an optical-electrical double-feedback technique. The emitted
      power concentration within the stabilized field spectrum was 81%. The minimum
      value of the square root of the Allan variance for the frequency stability was
      2.4 x 10(-14) at the integration time of 70 msec.

PMID- 19771121
TI  - Efficient short-pulse generation from a diode-pumped Nd:YLF laser with a
      piezoelectrically induced diffraction modulator.
AB  - The operation of a Nd:YLF laser pumped by a cw 1-W diode and mode locked by a
      piezoelectrically induced strainoptic light modulator is described. Pulse
      durations of 7 psec with 160 mW of output power have been achieved at a
      repetition rate of 160 MHz.

PMID- 19771122
TI  - Ultrashort-laser-pulse amplification in a XeF[C --> A] excimer amplifier.
AB  - Tunable blue-green subpicosecond laser pulses have been amplified in an electron
      beam-pumped XeF(C --> A) excimer amplifier. Small-signal gains of 3.5% cm(-1)
      were measured using a 50-cm active gain length. At output energy densities as
      high as 170 mJ/cm(2), only a small degree of saturation occurred, resulting in a
      gain of 2.5% cm(-1).

PMID- 19771123
TI  - Second-harmonic generation of femtosecond pulses: observation of phase-mismatch
      effects.
AB  - We observe new effects in frequency doubling of colliding-pulse, mode-locked dye
      amplified pulses (300 fsec, 620 nm, up to 1 mJ of energy) due to phase mismatch.
      If the second-harmonic generation in the nonlinear crystal (30-mm KDP crystal) is
      phase matched, the output is a square pulse. In contrast, when a phase mismatch
      is introduced, the generated pulse contains two peaks. We observe that the time
      profile is affected by depletion and chirp of the fundamental. The experimental
      results agree well with our numerical calculations.

PMID- 19771124
TI  - Active mode locking of a neodymium-doped fiber laser using intracavity pulse
      compression.
AB  - Active mode locking of a Nd(3+)-doped fiber laser with piezoelectrically induced
      Raman-Nath diffraction modulation is demonstrated. By using intracavity pulse
      compression, stable pulses of 2.4-psec length are generated at a wavelength of
      1054 nm.

PMID- 19771125
TI  - Bistable optical switching using electrochemically generated bubbles.
AB  - We demonstrate a novel bistable optical waveguide switch, which may be suitable
      for incorporation in large-dimension optical cross connects. The switching is
      based on the electrolytic creation and catalytic destruction of bubbles and is
      both wavelength and polarization independent. Calculations indicate that low
      losses and cross talk, which are crucial for large switching arrays, can be
      achieved with the combination of materials used in the prototype. The intrinsic
      bistability of the switch eliminates the need for a holding voltage and permits
      matrix addressing.

PMID- 19771126
TI  - Recording reconfigurable binary computer-generated holograms on bistable
      optically addressed ferroelectric liquid-crystal spatial light modulators.
AB  - The capacity of optically addressed bistable ferroelectric liquid-crystal spatial
      light modulators to be used for recording binary computer-generated holograms is
      experimentally demonstrated. The recording and reconstruction of cell- and point
      oriented holograms are presented.

PMID- 19771127
TI  - Quantum frequency conversion.
AB  - An experimental scheme is proposed by which the quantum states of two light beams
      of different frequencies can be interchanged. With this scheme it is possible to
      generate frequency-tunable squeezed light for spectroscopic applications.

PMID- 19771129
TI  - Optically addressed variable-efficiency waveguide grating for switching arrays.
AB  - An optically addressed waveguide grating switch is described and demonstrated.
      Its structure includes a planar slab waveguide with a surface relief grating and
      an active-material cladding layer. Photoinduced birefringence due to a polarized
      argon laser beam causes modulation of the refractive index of the cladding in the
      grating region and modulation of diffraction efficiency of the waveguide grating.

PMID- 19771128
TI  - Decreased damping of ultracold atoms in optical molasses: predictions and a
      possible solution.
AB  - We derive expressions for the damping rate for a two-level atom trapped in the
      antinodes of an optical interference pattern. We find that the decay rate is much
      slower than the rate for untrapped atoms in optical molasses. Although the
      velocity of untrapped atoms decays exponentially in time, the velocity of trapped
      atoms decays only as t(-(1/2)). We show that the slow damping rate can be
      circumvented by the addition of a traveling-wave component to the molasses
      standing wave and discuss how these results can be extended to multilevel atoms.

PMID- 19771130
TI  - Anomalous light scattering from a perturbed grating.
AB  - Both diffraction orders and backscattering enhancement have been observed in
      light scattering from a metallic diffraction grating with random groove depths.
      The polarization dependence of the observations is shown to be consistent with
      multiple-scattering models.

PMID- 19771132
TI  - Polymorphisms of the immune response genes: selected biological, methodical and
      medical aspects.
AB  - BACKGROUND: Variants of the immune response genes (IRG) are considered a
      potential source of interindividual differences in both innate and adaptive
      immune responses. A large number of gene polymorphisms have been reported as
      alternative forms of the IRG nucleotide sequence with important functional
      consequences for the structure/expression of immune response molecules.
      Accordingly, IRG polymorphisms are considered responsible for various monogenic
      diseases. They may also affect individual predisposition to complex diseases or
      modify their clinical course. METHODS AND RESULTS: In this review we define IRG
      polymorphism including its potential functionality. Common approaches used for
      the investigation of IRG polymorphisms are next briefly described. We then review
      current approaches (including genome-wide studies) for assessing the importance
      of particular IRG variants in the susceptibility to and clinical course of
      complex diseases. Finally, based on our own experience and on the literature, we
      illustrate current knowledge of the genetic component of two selected complex
      diseases (sarcoidosis and coronary artery disease). CONCLUSIONS: Despite major
      advances in genotyping technology and general knowledge of the implications of
      IRG in the susceptibility to complex diseases, the potential clinical application
      of these approaches still faces major challenges.

PMID- 19771133
TI  - Saliva as a diagnostic medium.
AB  - BACKGROUND: This is a review of current knowledge on the use of saliva, gingival
      cervical fluid and mucosal transudate in the detection of some oral and systemic
      diseases as well as drugs. Oral fluid is a diagnostic medium that can be easily
      collected and with minimal invasion but it has been neglected in the past. Today,
      saliva is being used more often to diagnose: HIV virus, oro-facial and systemic
      tumors, cardiovascular disease and in detecting addictive substances. Neutropil
      levels in saliva may also indicate successful bone marrow transplant. Oral fluid
      is now systematically being researched and oral fluid analysis is being compared
      with the analysis of other diagnostic media such as blood and urine. A number of
      recent studies have focused on oncogenic marker detection and its monitoring in
      saliva. The latest clinical and laboratory findings on diagnostic markers of
      oropharyngeal carcinoma in oral fluid could be the beginning of their wider use
      as a diagnostic medium. Oral fluid can also be also used to diagnose other
      malignancies such as breast cancer which was one of the first malignant tumors to
      be detected using genetic protein biomarkers. Raised levels of CA15-3 and the
      epidermal growth factor (EGF) receptor have been found in patients with breast
      cancer and elevated levels of CA 125 and the glycoprotein complex in the saliva
      of ovarian cancer patients. CONCLUSION: Doubtless, the diagnostic value of
      saliva, aided by current technological development will increase rapidly in the
      near future.

PMID- 19771134
TI  - Beta-glucan-indomethacin combination produces no lethal effects.
AB  - BACKGROUND: The most important quality of beta-glucans and the reason why so much
      attention has been devoted to them are their physiological effects. They are
      typical biological response modifiers with pronounced immunomodulating activity.
      However, some questions about possible side effects remain. AIM: Several papers
      reported the lethal side effects of non-steroidal anti-inflammatory drugs in
      glucan-treated mice, probably due to the peritonitis by enteric bacteria.
      However, these results were never independently confirmed. The purpose of this
      study is to evaluate these claims using several different types of glucans.
      METHODS: Effects of combined treatment with four different types of glucans and
      indomethacin were measured by evaluation of phagocytosis of HEMA particles by
      peripheral blood leukocytes and production of IL-6 in mouse serum. In addition,
      the level of blood glucose, colon length and survival after 30 days of treatment
      was measured. RESULTS: Our finding showed that simultaneous treatment with glucan
      and indomethacin caused a small decrease of phagocytic activity and IL-2
      production. Two other tested parameters-blood glucose levels and colon length
      that had been found to be significantly affected by this treatment, were
      virtually unchanged. In the final, yet most important part of the study, we found
      absolutely no mortality, regardless of the type of glucan or the routes of glucan
      administration. CONCLUSION: No adverse negative effects due to simultaneous
      treatment with glucan and non-steroidal anti-inflammatory drug dose was found,
      despite testing two different routes of glucan administration and four different
      types of glucan.

PMID- 19771135
TI  - Changes in clusterin serum concentration levels in oncologic patients during the
      course of spa therapy--a pilot study.
AB  - BACKGROUND: Clusterin (70-80 kDa; synonym ApoJ) is a stress-associated
      cytoprotective glycoprotein involved in many physiological and pathophysiological
      processes and it is up-regulated by various apoptotic triggers in many cancers
      and neurodegenerative diseases. AIM: Measurement of serum clusterin values in
      individuals with a history of cancer before and after spa therapy. METHODS: Serum
      clusterin concentration (ELISA) was determined in a group of 26 oncologic
      patients (4 men and 22 women) at the beginning and at the end (the 18th or 19th
      day) of spa treatment. The spa treatment lasted 3 weeks. The patients with
      various types of cancer had undergone basic therapy (surgery, chemotherapy,
      actinotherapy) prior to spa treatment. They were divided according to the
      interval between the end of basic treatment and the start of spa therapy.
      Patients coming within 12 months comprised group A (n=15) while patients coming
      later comprised group B (n=11). RESULTS: clusterin concentrations increased in 11
      patients (73%) and decreased in 4 (27%) in group A and increased in 5 (45%) and
      decreased in 6 (55%) in group B. The non-parametric sign test was non
      significant. There were positive value of average change between the second and
      the first sample in group A and negative value in group B. In group A the
      parametric test showed significant increased clusterin concentration at the end
      of spa treatment but the data had non-parametric distribution in fact.
      CONCLUSION: It is concluded that early spa therapy increases clusterin serum
      concentration. This is probably due to to the positive effects of balneotherapy.
      However the sample was very small and further research is required.

PMID- 19771136
TI  - Hematopoietic stem cell separation for experimental purposes--methodic
      limitations.
AB  - BACKGROUND: Protooncogene CD117 is a cytokine receptor important for
      hematopoietic element development. Currently, we are not able to routinely
      separate a sufficient quantity of bone marrow CD117+ cells for experimental
      purposes. AIM: The aim of this study was to establish an immunomagnetic
      separation method for CD117+ hematopoietic stem cell isolation and to estimate
      the expression of chosen BCl-2 family protein members in these elements. MATERIAL
      AND METHODS: 120 samples of human and murine bone marrow were acquired using the
      magnetic separation system. The cells were stained for CD117, BCl-2, BAX, and
      CD33 by an indirect fluorescent immunocytochemistry. RESULTS: The flow cytometry
      analysis showed only 2.6% CD117+ cells from human as well as mouse bone marrow
      which is insufficient for further experiments. Cytospin was not good for
      morphologic characterization and immunophenotyping due to the fragility and
      destruction of the studied cells. Therefore, cell suspension staining was
      selected and by this method we found CD117 positivity in 70% of the mononuclerar
      (CD33 positive) elements in the case of chronic myeloid leukaemia. Labelling of
      the BCl-2 family in this case showed antiapoptotic BCl-2 expression in 80 %,
      proapoptotic BAX expression in approximately 5%. CONCLUSION: Our results show
      that CD117 immunomagnetic separation from bone marrow material is not acceptable
      for experimental purposes. They demonstrate that the only practical useful for
      the bone marrow cell examination (morphology and immunophenotype) is cell
      suspension staining which uncovers the distribution of both cytoplasmic proteins
      and surface antigens of immature blood elements.

PMID- 19771137
TI  - Inducible nitric oxide synthase modulates angiogenesis in ischemic hindlimb of
      rat.
AB  - BACKGROUND: Angiogenesis plays an important role in maintaining adequate oxygen
      delivery, and nitric oxide (NO) is a potential regulator of angiogenesis. NO is
      synthesized through three isoforms of NO synthase (NOS). It is hypothesized that
      the NO derived from inducible NOS (iNOS) may promote survival of ischemic tissue
      through angiogenesis. To test this hypothesis, we investigated the effect of iNOS
      deficiency (by L-NIL) on angiogenesis in a hindlimb ischemia model. METHODS:
      Thirty-two male wistar rats randomly divided into four groups. In groups 1 & 2,
      hindlimb ischemia was induced by ligation of femoral artery and they received L
      NIL and saline respectively. The animals in groups 3 and 4 also received L-NIL
      and saline respectively without surgical procedure. After 21 days, the serum
      concentration of nitrite, capillary density and expression of HIF1alpha were
      determined. RESULTS: Serum nitrite levels were significantly lower in L-NIL
      groups (p<0.05). The capillary density in group 1 (ischemia+L-NIL) was
      significantly different from group 2 (ischemia+saline); group 1: 360.33+/-77.02,
      group 2: 549+/-81.85 /mm2, p<0.05) .In addition, expression of HIF1alpha was
      significantly increased in ischemic groups (p<0.05). CONCLUSION: Selective
      inhibition of iNOS by L-NIL inhibits angiogenesis in a hindlimb ischemic rat
      model. In addition, ischemia induces expression of HIF1alpha in hypoxic tissue.

PMID- 19771138
TI  - Pictorial cognitive task resolution and expired minute ventilation, oxygen
      consumption, carbon dioxide production and heart rate.
AB  - AIMS: To assess the impact of cognitive task solving on respiratory and
      cardiovascular parameters. METHODS: The ML870B80 Exercise Physiology System was
      used to record concurrently with EEG, the cardiorespiratory and metabolic
      functions of subjects during cognitive activity. The Expired Minute Ventilation
      (VE), Oxygen Consumption (VO2), Carbon Dioxide Production (VCO2) and Average
      Heart Rate (BPM) were ascertained for four periods: (1) rest or starting period,
      (2) reference period, (3) cognitive task solving period and (4) recovery period.
      Each period was defined by the type of presented visual stimuli and by the
      prearranged cognitive activity related to visual stimuli. The personality traits
      of participants were also determined. RESULTS: The momentary functional state of
      subject's brain (i.e. the period of the experiment) determined the average values
      of all measured parameters. During the cognitive task solving period the average
      VE, VO2 and VCO2 reached the lowest values while the HR behaved reversely--it was
      the highest in the cognitive task solving period. Further, the average VE, VCO2
      and HR values but not VO2 value differed significantly from average values for
      the same variable measured in the rest period. CONCLUSION: The changes in
      respiratory variables during the cognitive task solving period predicate the
      whole-body metabolic rate rather than the energy metabolism of the brain alone.
      However, the heart rate related to some personality traits of the subject has a
      tighter relation to brain's energy metabolic rate during the cognitive task
      solving--it affects the oxygen supply of the brain.

PMID- 19771140
TI  - Two varieties of honey that are available in Malaysia gave intermediate glycemic
      index values when tested among healthy individuals.
AB  - AIM: To determine the glycemic index (GI) of Malaysian wild honey and Australian
      honey. METHODS: Eight healthy volunteers (5 men and 3 women, aged 24-44 y, with
      normal BMI) were served 50 g carbohydrate portions of two varieties of honey or
      the reference food (glucose, tested 3 times), on separate occasions. Capillary
      blood glucose was measured fasting and at 15, 30, 45, 60, 90 and 120 min after
      the start of the test meals. The GI was calculated by expressing each subject's
      incremental area under the blood glucose curve (AUC) after honey as a percentage
      of his or her mean AUC after glucose. RESULTS: The results showed that the mean
      AUC of the Malaysian and Australian honeys, 174+/-19 and 158+/-16 mmolxmin/l,
      respectively, did not differ from each other but were significantly less than
      that after glucose, 259+/-15 mmolxmin/l (P<0.001). The mean GI of Malaysian wild
      honey, 65+/-7, did not differ from that of Australian honey, 59+/-5, but both
      were significantly less than the GI of glucose, 100 (P<0.001). CONCLUSIONS: We
      conclude that both Malaysian wild honey (GI=65+/-7) and Australian honey (GI=59+/
      5) are intermediate GI foods.

PMID- 19771139
TI  - Assessment of haemoglobin a1c evolution using two statistical approaches
      (survival analysis and linear regression) in persons with diabetes mellitus.
AB  - BACKGROUND: Intensive selfmonitoring is an important and cost-demanding part of
      diabetes treatment. Continuous glucose monitoring (CGM) using transcutaneous
      sensors offers "real time" information on glycemia. In the present study, we
      assessed the therapeutic efficacy of CGM on metabolic control using two different
      statistical methods: linear regression and "survival analysis". OBJECTIVES: (1)
      to assess the therapeutic efficacy of CGM on metabolic control using two
      different statistical methods: linear regression and survival analysis; (2) to
      demonstrate the particular advantages of each statistical method. METHODS: A
      total of 42 persons with diabetes mellitus treated by means of an insulin pump
      participated in this study. According to the means of selfmonitoring persons with
      diabetes were divided into two groups: 1. intervention group of 17 persons using
      CGM, 2. control group of 25 persons using a glucometer. Each person was followed
      for a period of three months. At the beginning of the study and at the end of
      each month HbA1c was determined. RESULTS: Both the regression analysis and
      survival analysis brought evidence of significant changes of the HbA1c in either
      of the groups. The method of linear regression enables to analyse the evolution
      of HbA1c in each individual person followed by comparison of the groups. The
      survival analysis demonstrated that the probability of HbA1c decrease to the
      predefined level as well as its further maintaining at this level was higher in
      the CGM group. The mean time interval necessary to HbA1c decrease was shorter in
      the CGM group. CONCLUSIONS: The efficacy of CGM was demonstrated. In addition to
      linear regression, survival analysis appears to be an useful complementary method
      in the statistical evaluation of the treatment efficacy.

PMID- 19771141
TI  - Assessment of the relation of the optic nerve to the posterior ethmoid and
      sphenoid sinuses by computed tomography.
AB  - OBJECTIVE: The aim of this study was to observe the relationship of the sphenoid
      sinus and posterior ethmoid cells with the optic nerve. MATERIAL AND METHODS: 34
      CT scans (68 sides) of paranasal sinuses of patients older than 18 years were
      retrospectively reviewed. Images were assessed in two planes--axial and coronal.
      We observed the position and relationship of the optic nerve to the posterior
      ethmoid and sphenoid sinuses, bony dehiscence and protrusion of the optic nerve
      into sinuses, and pneumatization of the anterior clinoid process. RESULTS: The
      most frequent position of optic nerve (ON) was a location close to the posterior
      ethmoid and sphenoid sinuses without contacting or indentation of the wall--55.9%
      (38 nerves). The bulging of ON to sphenoid sinus was found in 14.7% (10 nerves)
      and the course of the nerve through sinus in 16 nerves (23.5%). The position of
      ON intimately to both sinuses was observed in 5.9% (4 nerves). Protrusion of ON,
      dehiscence of the bony wall and pneumatization of anterior clinoid process (ACP)
      was seen in 12 (35.3%), 4 (11.8%) and 9 (26.5%) patients, respectively. Both the
      protrusion of ON and ACP pneumatization were present in 8 (23.5%) patients on the
      right side and in 5 (14.7%) patients on the left side. CONCLUSION: Variations of
      posterior ethmoid and sphenoid sinuses are numerous and may entail potential risk
      of injury of the ON during sinus surgery. Knowledge of individual differences and
      configurations in the operation area may help the surgeon to prevent
      complications. Computed tomography is the preferred radiographic modality for
      evaluation of bony variations and the pathology of this region.

PMID- 19771142
TI  - Is the biliary manometric perfusion test effective in the evaluation of balloon
      dilatation treatment success of benign biliary strictures?
AB  - BACKGROUND: The success of balloon dilatation treatment of benign biliary
      strictures (BBS) is usually evaluated by 'clinical test'. For objective
      evaluation of treatment success, measurement of the pressure inside the biliary
      tree after treatment has been proposed. AIM: The aim of this article is to assess
      the role of biliary manometric perfusion test (BMPT) in the evaluation of
      treatment success of BBS and to assess the long term biliary patency after
      evaluation by BMPT. MATERIALS AND METHODS: From February 2003 to January 2008, 12
      patients (median age 53.5 years) after balloon dilatation treatment were
      evaluated by BMPT. BMPT was done after a mean of 3 dilatations over a mean period
      of 6.85 months. An intrabiliary pressure less than 20 cm of water during the test
      was considered as success threshold. RESULTS: The pressures during BMPT were less
      than 20 cm of water in 11 out of 12 patients. Subsequently the drain was removed
      and patients were followed up clinically. Two patients on follow-up required re
      intervention 13 days and 11 months later. The remaining 9 patients had no
      evidence of biliary obstruction at a mean following of 15.3 months. Using the
      statistical Kaplan-Meier analysis, the probability of biliary patency up to 9
      months was 90.9% and at 1, 2 and 3 years was 77%. CONCLUSION: BMPT is effective
      in the evaluation of treatment success of BBS. It is simple, cost effective,
      gives immediate results and helps us to determine the treatment end point.

PMID- 19771143
TI  - Mistakes in the usage of anatomical terminology in clinical practice.
AB  - BACKGROUND: Anatomical terminology serves as a basic communication tool in all
      the medical fields. Therefore Latin anatomical nomenclature has been repetitively
      issued and revised from 1895 (Basiliensia Nomina Anatomica) until 1998, when the
      last version was approved and published as the Terminologia Anatomica
      (International Anatomical Terminology) by the Federative Committee on Anatomical
      Terminology. METHODS AND RESULTS: A brief history of the terminology and
      nomenclature development is mentioned, along with the concept and contributions
      of the Terminologia Anatomica including the employed abbreviations. Examples of
      obsolete anatomical terms and their current synonyms are listed. Clinicians
      entered the process of the nomenclature revision and this aspect is demonstrated
      with several examples of terms used in clinical fields only, some already
      incorporated in the Terminologia Anatomica and a few obsolete terms still alive
      in non-theoretical communication. Frequent mistakes in grammar and orthography
      are stated as well. CONCLUSION: Authors of the article strongly recommend the use
      of the recent revision of the Latin anatomical nomenclature both in theoretical
      and clinical medicine.

PMID- 19771144
TI  - Substance use and knowledge among Italian high school students.
AB  - AIMS: This study was aimed for evaluation of Italian students' attitudes to
      addictive substances, their knowledge and personal experience, and their
      awareness about the risks. METHODS: The research was realized among high school
      students from Marche region in the Central Italy in the year 2006; the study
      group was randomly chosen from all schools in the region. 4118 appropriately
      completed questionnaires returned. The statistic processing was carried out by
      using chi-square test for two qualitative variables.

PMID- 19771145
TI  - Effects of protein subunits removal on the computed motions of partial 30S
      structures of the ribosome.
AB  - The Anisotropic Network Model (ANM) is used to study motions of the 30S small
      ribosomal subunit. The effect of the absence of certain subunits on the motions
      of the remaining partial structures was investigated by removing one protein,
      pairs of proteins and selected sets of proteins at a time. Our results show that
      the removal of some proteins doesn't change the large-scale dynamics of the
      partial structures, but the removal of certain subunits does cause significant
      changes in motion of the remaining structure, and these changes can be reverted
      by the removal of other subunits, which indicates interdependence between motions
      of various parts of the 30S ribosomal structure. We further found that the
      subunits showing such interdependence have strong positive correlation of their
      motions, which indicates that these subunits function as a unit block in the 30S
      small ribosomal subunit. Dynamically interdependent subunit pairs identified in
      this paper are consistent with previous experimental observations that suggested
      dimerization of those subunits.

PMID- 19771146
TI  - Midline signalling systems direct the formation of a neural map by dendritic
      targeting in the Drosophila motor system.
AB  - A fundamental strategy for organising connections in the nervous system is the
      formation of neural maps. Map formation has been most intensively studied in
      sensory systems where the central arrangement of axon terminals reflects the
      distribution of sensory neuron cell bodies in the periphery or the sensory
      modality. This straightforward link between anatomy and function has facilitated
      tremendous progress in identifying cellular and molecular mechanisms that
      underpin map development. Much less is known about the way in which networks that
      underlie locomotion are organised. We recently showed that in the Drosophila
      embryo, dendrites of motorneurons form a neural map, being arranged
      topographically in the antero-posterior axis to represent the distribution of
      their target muscles in the periphery. However, the way in which a dendritic
      myotopic map forms has not been resolved and whether postsynaptic dendrites are
      involved in establishing sets of connections has been relatively little explored.
      In this study, we show that motorneurons also form a myotopic map in a second
      neuropile axis, with respect to the ventral midline, and they achieve this by
      targeting their dendrites to distinct medio-lateral territories. We demonstrate
      that this map is "hard-wired"; that is, it forms in the absence of excitatory
      synaptic inputs or when presynaptic terminals have been displaced. We show that
      the midline signalling systems Slit/Robo and Netrin/Frazzled are the main
      molecular mechanisms that underlie dendritic targeting with respect to the
      midline. Robo and Frazzled are required cell-autonomously in motorneurons and the
      balance of their opposite actions determines the dendritic target territory. A
      quantitative analysis shows that dendritic morphology emerges as guidance cue
      receptors determine the distribution of the available dendrites, whose total
      length and branching frequency are specified by other cell intrinsic programmes.
      Our results suggest that the formation of dendritic myotopic maps in response to
      midline guidance cues may be a conserved strategy for organising connections in
      motor systems. We further propose that sets of connections may be specified, at
      least to a degree, by global patterning systems that deliver pre- and
      postsynaptic partner terminals to common "meeting regions."

PMID- 19771147
TI  - Dendritic targeting in the leg neuropil of Drosophila: the role of midline
      signalling molecules in generating a myotopic map.
AB  - Neural maps are emergent, highly ordered structures that are essential for
      organizing and presenting synaptic information. Within the embryonic nervous
      system of Drosophila motoneuron dendrites are organized topographically as a
      myotopic map that reflects their pattern of innervation in the muscle field. Here
      we reveal that this fundamental organizational principle exists in adult
      Drosophila, where the dendrites of leg motoneurons also generate a myotopic map.
      A single postembryonic neuroblast sequentially generates different leg motoneuron
      subtypes, starting with those innervating proximal targets and medial neuropil
      regions and producing progeny that innervate distal muscle targets and lateral
      neuropil later in the lineage. Thus the cellular distinctions in peripheral
      targets and central dendritic domains, which make up the myotopic map, are linked
      to the birth-order of these motoneurons. Our developmental analysis of dendrite
      growth reveals that this myotopic map is generated by targeting. We demonstrate
      that the medio-lateral positioning of motoneuron dendrites in the leg neuropil is
      controlled by the midline signalling systems Slit-Robo and Netrin-Fra. These
      results reveal that dendritic targeting plays a major role in the formation of
      myotopic maps and suggests that the coordinate spatial control of both pre- and
      postsynaptic elements by global neuropilar signals may be an important mechanism
      for establishing the specificity of synaptic connections.

PMID- 19771148
TI  - Negative regulation of active zone assembly by a newly identified SR protein
      kinase.
AB  - Presynaptic, electron-dense, cytoplasmic protrusions such as the T-bar
      (Drosophila) or ribbon (vertebrates) are believed to facilitate vesicle movement
      to the active zone (AZ) of synapses throughout the nervous system. The molecular
      composition of these structures including the T-bar and ribbon are largely
      unknown, as are the mechanisms that specify their synapse-specific assembly and
      distribution. In a large-scale, forward genetic screen, we have identified a
      mutation termed air traffic controller (atc) that causes T-bar-like protein
      aggregates to form abnormally in motoneuron axons. This mutation disrupts a gene
      that encodes for a serine-arginine protein kinase (SRPK79D). This mutant
      phenotype is specific to SRPK79D and is not secondary to impaired kinesin
      dependent axonal transport. The srpk79D gene is neuronally expressed, and
      transgenic rescue experiments are consistent with SRPK79D kinase activity being
      necessary in neurons. The SRPK79D protein colocalizes with the T-bar-associated
      protein Bruchpilot (Brp) in both the axon and synapse. We propose that SRPK79D is
      a novel T-bar-associated protein kinase that represses T-bar assembly in
      peripheral axons, and that SRPK79D-dependent repression must be relieved to
      facilitate site-specific AZ assembly. Consistent with this model, overexpression
      of SRPK79D disrupts AZ-specific Brp organization and significantly impairs
      presynaptic neurotransmitter release. These data identify a novel AZ-associated
      protein kinase and reveal a new mechanism of negative regulation involved in AZ
      assembly. This mechanism could contribute to the speed and specificity with which
      AZs are assembled throughout the nervous system.

PMID- 19771149
TI  - Molecular basis of rare aminoglycoside susceptibility and pathogenesis of
      Burkholderia pseudomallei clinical isolates from Thailand.
AB  - BACKGROUND: Burkholderia pseudomallei is intrinsically resistant to
      aminoglycosides and macrolides, mostly due to AmrAB-OprA efflux pump expression.
      We investigated the molecular mechanisms of aminoglycoside susceptibility
      exhibited by Thai strains 708a, 2188a, and 3799a. METHODOLOGY/PRINCIPAL FINDINGS:
      qRT-PCR revealed absence of amrB transcripts in 708a and greatly reduced levels
      in 2188a and 3799a. Serial passage on increasing gentamicin concentrations
      yielded 2188a and 3799a mutants that became simultaneously resistant to other
      aminoglycosides and macrolides, whereas such mutants could not be obtained with
      708a. Transcript analysis showed that the resistance of the 2188a and 3799a
      mutants was due to upregulation of amrAB-oprA expression by unknown mechanism(s).
      Use of a PCR walking strategy revealed that the amrAB-oprA operon was missing in
      708a and that this loss was associated with deletion of more than 70 kb of
      genetic material. Rescue of the amrAB-oprB region from a 708a fosmid library and
      sequencing showed the presence of a large chromosome 1 deletion (131 kb and 141
      kb compared to strains K96243 and 1710b, respectively). This deletion not only
      removed the amrAB-oprA operon, but also the entire gene clusters for malleobactin
      and cobalamin synthesis. Other genes deleted included the anaerobic arginine
      deiminase pathway, putative type 1 fimbriae and secreted chitinase. Whole genome
      sequencing and PCR analysis confirmed absence of these genes from 708a. Despite
      missing several putative virulence genes, 708a was fully virulent in a murine
      melioidosis model. CONCLUSIONS/SIGNIFICANCE: Strain 708a may be a natural
      candidate for genetic manipulation experiments that use Select Agent compliant
      antibiotics for selection and validates the use of laboratory-constructed
      Delta(amrAB-oprA) mutants in such experiments.

PMID- 19771150
TI  - Rapid identification of paragonimiasis foci by lay informants in Lao People's
      Democratic Republic.
AB  - BACKGROUND: Paragonimiasis is a food-borne trematodiasis leading to lung disease.
      Worldwide, an estimated 21 million people are infected. Foci of ongoing
      transmission remain often unnoticed. We evaluated a simple questionnaire approach
      using lay-informants at the village level to identify paragonimiasis foci and
      suspected paragonimiasis cases. METHODOLOGY/PRINCIPAL FINDINGS: The study was
      carried out in an endemic area of Lao People's Democratic Republic. Leaders of 49
      remote villages in northern Vientiane Province were asked to notify suspected
      paragonimiasis patients using a four-item questionnaire sent through
      administrative channels: persons responding positively for having chronic cough
      (more than 3 weeks) and/or blood in sputum with or without fever. We validated
      the village leaders' reports in ten representative villages with a door-to-door
      survey. We examined three sputa of suspected patients for the presence of
      Paragonimus eggs and acid fast bacilli. 91.8% of village leaders participated and
      notified a total of 220 suspected patients; 76.2% were eventually confirmed; an
      additional 138 suspected cases were found in the survey. Sensitivity of village
      leaders' notice for "chronic cough" and "blood in sputum" was 100%; "blood in
      sputum" alone reached a sensitivity of 85.7%. SIGNIFICANCE: Our approach led to
      the identification of three previously unknown foci of transmission. A rapid and
      simple lay-informant questionnaire approach is a promising low-cost community
      diagnostic tool of paragonimiasis control programs.

PMID- 19771151
TI  - Natural infection of the ground squirrel (Spermophilus spp.) with Echinococcus
      granulosus in China.
AB  - BACKGROUND: Echinococcus granulosus is usually transmitted between canid
      definitive hosts and ungulate intermediate hosts. METHODOLOGY/PRINCIPAL FINDINGS:
      Lesions found in the livers of ground squirrels, Spermophilus
      dauricus/alashanicus, trapped in Ningxia Hui Autonomous Region, an area in China
      co-endemic for both E. granulosus and E. multilocularis, were subjected to
      molecular genotyping for Echinococcus spp. DNA. One of the lesions was shown to
      be caused by E. granulosus and subsequently by histology to contain viable
      protoscoleces. CONCLUSIONS/SIGNIFICANCE: This is the first report of a natural
      infection of the ground squirrel with E. granulosus. This does not provide
      definitive proof of a cycle involving ground squirrels and dogs or foxes, but it
      is clear that there is active E. granulosus transmission occurring in this area,
      despite a recent past decline in the dog population in southern Ningxia.

PMID- 19771152
TI  - In silico reconstitution of actin-based symmetry breaking and motility.
AB  - Eukaryotic cells assemble viscoelastic networks of crosslinked actin filaments to
      control their shape, mechanical properties, and motility. One important class of
      actin network is nucleated by the Arp2/3 complex and drives both membrane
      protrusion at the leading edge of motile cells and intracellular motility of
      pathogens such as Listeria monocytogenes. These networks can be reconstituted in
      vitro from purified components to drive the motility of spherical micron-sized
      beads. An Elastic Gel model has been successful in explaining how these networks
      break symmetry, but how they produce directed motile force has been less clear.
      We have combined numerical simulations with in vitro experiments to reconstitute
      the behavior of these motile actin networks in silico using an Accumulative
      Particle-Spring (APS) model that builds on the Elastic Gel model, and
      demonstrates simple intuitive mechanisms for both symmetry breaking and sustained
      motility. The APS model explains observed transitions between smooth and
      pulsatile motion as well as subtle variations in network architecture caused by
      differences in geometry and conditions. Our findings also explain sideways
      symmetry breaking and motility of elongated beads, and show that elastic recoil,
      though important for symmetry breaking and pulsatile motion, is not necessary for
      smooth directional motility. The APS model demonstrates how a small number of
      viscoelastic network parameters and construction rules suffice to recapture the
      complex behavior of motile actin networks. The fact that the model not only
      mirrors our in vitro observations, but also makes novel predictions that we
      confirm by experiment, suggests that the model captures much of the essence of
      actin-based motility in this system.

PMID- 19771153
TI  - Improving the quantitative basis of the surgical burden in low-income countries.

PMID- 19771154
TI  - Human angiostrongyliasis outbreak in Dali, China.
AB  - BACKGROUND: Several angiostrongyliasis outbreaks have been reported in recent
      years but the disease continues to be neglected in public health circles. We
      describe an outbreak in Dali, southwest China in order to highlight some key
      problems for the control of this helminth infection. METHODOLOGY/PRINCIPAL
      FINDINGS: All available medical records of suspected angiostrongyliasis patients
      visiting hospitals in Dali in the period 1 October 2007-31 March 2008 were
      reviewed, and tentative diagnoses of varying strengths were reached according to
      given sets of criteria. Snails collected from local markets, restaurants and
      natural habitats were also screened for the presence of Angiostrongylus
      cantonensis. A total of 33 patients met criteria for infection, and 11 among them
      were classified as clinically confirmed. An additional eight patients were
      identified through a surveillance system put in operation in response to the
      outbreak. The epidemic lasted for 8 months with its peak in February 2008. Of the
      33 patients, 97.0% complained of severe headache. 84.8% patients had high
      eosinophil cell counts either in the peripheral blood or in cerebrospinal fluid
      (CSF). Three-quarters of the patients were treated with a combination of
      albendazole and corticosteroids, resulting in significantly improved overall
      conditions. Twenty-two patients reported the consumption of raw or undercooked
      snails prior to the onset of the symptoms, and approximately 1.0% of the Pomacea
      canaliculata snails on sale were found to be infected with A. cantonensis. The
      snails were also found in certain habitats around Dali but no parasites were
      detected in these populations. CONCLUSIONS/SIGNIFICANCE: The import and sale of
      infected P. canaliculata is the likely trigger for this angiostrongyliasis
      outbreak. Awareness of angiostrongyliasis must be raised, and standardized
      diagnosis and treatment are needed in order to provide clinicians with a guide to
      address this disease. Health education campaigns could limit the risk, and a
      hospital-based surveillance system should be established in order to detect
      future outbreaks.

PMID- 19771155
TI  - The feasibility of using high resolution genome sequencing of influenza A viruses
      to detect mixed infections and quasispecies.
AB  - BACKGROUND: The rapidly expanding availability of de novo sequencing technologies
      can greatly facilitate efforts to monitor the relatively high mutation rates of
      influenza A viruses and the detection of quasispecies. Both the mutation rates
      and the lineages of influenza A viruses are likely to play an important role in
      the natural history of these viruses and the emergence of phenotypically and
      antigenically distinct strains. METHODOLOGY AND PRINCIPAL FINDINGS: We evaluated
      quasispecies and mixed infections by de novo sequencing the whole genomes of 10
      virus isolates, including eight avian influenza viruses grown in embryonated
      chicken eggs (six waterfowl isolates - five H3N2 and one H4N6; an H7N3 turkey
      isolate; and a bald eagle isolate with H1N1/H2N1 mixed infection), and two tissue
      cultured H3N2 swine influenza viruses. Two waterfowl cloacal swabs were included
      in the analysis. Full-length sequences of all segments were obtained with 20 to
      787-X coverage for the ten viruses and one cloacal swab. The second cloacal swab
      yielded 15 influenza reads of approximately 230 bases, sufficient for
      bioinformatic inference of mixed infections or quasispecies. Genomic
      subpopulations or quasispecies of viruses were identified in four egg grown avian
      influenza isolates and one cell cultured swine virus. A bald eagle isolate and
      the second cloacal swab showed evidence of mixed infections with two (H1 and H2)
      and three (H1, H3, and H4) HA subtypes, respectively. Multiple sequence
      differences were identified between cloacal swab and the virus recovered using
      embryonated chicken eggs. CONCLUSIONS: We describe a new approach to
      comprehensively identify mixed infections and quasispecies in low passage
      influenza A isolates and cloacal swabs and add to the understanding of the
      ecology of influenza A virus populations.

PMID- 19771156
TI  - The effect of changing patterns of obstetric care in Scotland (1980-2004) on
      rates of preterm birth and its neonatal consequences: perinatal database study.
AB  - BACKGROUND: Rates of preterm birth are rising worldwide. Studies from the United
      States and Latin America suggest that much of this rise relates to increased
      rates of medically indicated preterm birth. In contrast, European and Australian
      data suggest that increases in spontaneous preterm labour also play a role. We
      aimed, in a population-based database of 5 million people, to determine the
      temporal trends and obstetric antecedents of singleton preterm birth and its
      associated neonatal mortality and morbidity for the period 1980-2004. METHODS AND
      FINDINGS: There were 1.49 million births in Scotland over the study period, of
      which 5.8% were preterm. We found a percentage increase in crude rates of both
      spontaneous preterm birth per 1,000 singleton births (10.7%, p<0.01) and
      medically indicated preterm births (41.2%, p<0.01), which persisted when adjusted
      for maternal age at delivery. The greater proportion of spontaneous preterm
      births meant that the absolute increase in rates of preterm birth in each
      category were similar. Of specific maternal complications, essential and
      pregnancy-induced hypertension, pre-eclampsia, and placenta praevia played a
      decreasing role in preterm birth over the study period, with gestational and pre
      existing diabetes playing an increasing role. There was a decline in stillbirth,
      neonatal, and extended perinatal mortality associated with preterm birth at all
      gestation over the study period but an increase in the rate of prolonged hospital
      stay for the neonate. Neonatal mortality improved in all subgroups, regardless of
      obstetric antecedent of preterm birth or gestational age. In the 28 wk and
      greater gestational groups we found a reduction in stillbirths and extended
      perinatal mortality for medically induced but not spontaneous preterm births (in
      the absence of maternal complications) although at the expense of a longer stay
      in neonatal intensive care. This improvement in stillbirth and neonatal mortality
      supports the decision making behind the 34% increase in elective/induced preterm
      birth in these women. Although improvements in neonatal outcomes overall are
      welcome, preterm birth still accounts for over 66% of singleton stillbirths, 65%
      of singleton neonatal deaths, and 67% of infants whose stay in the neonatal unit
      is "prolonged," suggesting this condition remains a significant contributor to
      perinatal mortality and morbidity. CONCLUSIONS: In our population, increases in
      spontaneous and medically induced preterm births have made equal contributions to
      the rising rate of preterm birth. Despite improvements in related perinatal
      mortality, preterm birth remains a major obstetric and neonatal problem, and its
      frequency is increasing. Please see later in the article for the Editors'
      Summary.

PMID- 19771157
TI  - Serial examination of an inducible and reversible dilated cardiomyopathy in
      individual adult Drosophila.
AB  - Recent work has demonstrated that Drosophila can be used as a model of dilated
      cardiomyopathy, defined as an enlarged cardiac chamber at end-diastole when the
      heart is fully relaxed and having an impaired systolic function when the heart is
      fully contracted. Gene mutations that cause cardiac dysfunction in adult
      Drosophila can result from abnormalities in cardiac development or alterations in
      post-developmental heart function. To clarify the contribution of transgene
      expression to post-developmental cardiac abnormalities, we applied strategies to
      examine the temporal and spacial effects of transgene expression on cardiac
      function. We engineered transgenic Drosophila based on the well-characterized
      temperature-sensitive Gal80 protein in the context of the bipartite Gal4/UAS
      transgenic expression system in Drosophila employing the cardiac specific driver,
      tinCDelta4-Gal4. Then, we developed a strategy using optical coherence tomography
      to serially measure cardiac function in the individual flies over time course of
      several days. As a proof of concept we examined the effects of the expression of
      a human mutant delta-sarcoglycan associated with familial heart failure and
      observed a reversible, post-developmental dilated cardiomyopathy in Drosophila.
      Our results show that the unique imaging strategy based on the non-destructive,
      non-invasive properties of optical coherence tomography can be applied to
      serially examine cardiac function in individual adult flies. Furthermore, the
      induction and reversal of cardiac transgene expression can be investigated in
      adult flies thereby providing insight into the post-developmental effects of
      transgene expression.

PMID- 19771158
TI  - Down-regulation of platelet surface CD47 expression in Escherichia coli O157:H7
      infection-induced thrombocytopenia.
AB  - BACKGROUND: Platelet depletion is a key feature of hemolytic uremic syndrome
      (HUS) caused by Shiga toxin-producing Escherichia coli (STEC) infection. The
      mechanism underlying STEC-induced platelet depletion, however, is not completely
      understood. METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrated for the first
      time that platelet surface expression of CD47 was significantly decreased in
      C57BL6 mice treated with concentrated culture filtrates (CCF) from STEC O157:H7.
      STEC O157:H7 CCF treatment also led to a sharp drop of platelet counts. The
      reduction of cell surface CD47 was specific for platelets but not for neutrophil,
      monocytes and red blood cells. Down-regulation of platelet surface CD47 was also
      observed in isolated human platelets treated with O157:H7 CCF. Platelet surface
      CD47 reduction by O157:H7 CCF could be blocked by anti-TLR4 antibody but not anti
      CD62 antibody. Down-regulation of platelet surface CD47 was positively correlated
      with platelet activation and phagocytosis by human monocyte-derived macrophages.
      Furthermore, the enhanced phagocytosis process of O157:H7 CCF-treated platelets
      was abolished by addition of soluble CD47 recombinants. CONCLUSIONS/SIGNIFICANCE:
      Our results suggest that platelet CD47 down-regulation may be a novel mechanism
      underneath STEC-induced platelet depletion, and that the interactions between
      CD47 and its receptor, signal regulatory protein alpha (SIRPalpha), play an
      essential role in modulating platelet homeostasis.

PMID- 19771159
TI  - Effects of attention to auditory motion on cortical activations during smooth
      pursuit eye tracking.
AB  - BACKGROUND: In contrast to traditional views that consider smooth pursuit as a
      relatively automatic process, evidence has been reported for the importance of
      attention for accurate pursuit performance. However, the exact role that
      attention might play in the maintenance of pursuit remains unclear.
      METHODOLOGY/PRINCIPAL FINDINGS: We analysed the neuronal activity associated with
      healthy subjects executing smooth pursuit eye movements (SPEM) during concurrent
      attentive tracking of a moving sound source, which was either in-phase or in
      antiphase to the executed eye movements. Assuming that attentional resources must
      be allocated to the moving sound source, the simultaneous execution of SPEM and
      auditory tracking in diverging directions should result in increased load on
      common attentional resources. By using an auditory stimulus as a distractor
      rather then a visual stimulus we guaranteed that cortical activity cannot be
      caused by conflicts between two simultaneous visual motion stimuli. Our results
      revealed that the smooth pursuit task with divided attention led to significantly
      higher activations bilaterally in the posterior parietal cortex and lateral and
      medial frontal cortex, presumably containing the parietal, frontal and
      supplementary eye fields respectively. CONCLUSIONS: The additional cortical
      activation in these areas is apparently due to the process of dividing attention
      between the execution of SPEM and the covert tracking of the auditory target. On
      the other hand, even though attention had to be divided the attentional resources
      did not seem to be exhausted, since the identification of the direction of the
      auditory target and the quality of SPEM were unaffected by the congruence between
      visual and auditory motion stimuli. Finally, we found that this form of task
      related attention modulated not only the cortical pursuit network in general but
      also affected modality specific and supramodal attention regions.

PMID- 19771160
TI  - Diverse bone morphogenetic protein expression profiles and smad pathway
      activation in different phenotypes of experimental canine mammary tumors.
AB  - BACKGROUND: BMPs are currently receiving attention for their role in
      tumorigenesis and tumor progression. Currently, most BMP expression studies are
      performed on carcinomas, and not much is known about the situation in sarcomas.
      METHODOLOGY/PRINCIPAL FINDINGS: We have investigated the BMP expression profiles
      and Smad activation in clones from different spontaneous canine mammary tumors.
      Spindle cell tumor and osteosarcoma clones expressed high levels of BMPs, in
      particular BMP-2, -4 and -6. Clones from a scirrhous carcinoma expressed much
      lower BMP levels. The various clones formed different tumor types in nude mice
      but only clones that expressed high levels of BMP-6 gave bone formation.
      Phosphorylated Smad-1/5, located in the nucleus, was detected in tumors derived
      from clones expressing high levels of BMPs, indicating an active BMP signaling
      pathway and BMP-2 stimulation of mammary tumor cell clones in vitro resulted in
      activation of the Smad-1/5 pathway. In contrast BMP-2 stimulation did not induce
      phosphorylation of the non-Smad pathway p38 MAPK. Interestingly, an increased
      level of the BMP-antagonist chordin-like 1 was detected after BMP stimulation of
      non-bone forming clones. CONCLUSIONS/SIGNIFICANCE: We conclude that the specific
      BMP expression repertoire differs substantially between different types of
      mammary tumors and that BMP-6 expression most probably has a biological role in
      bone formation of canine mammary tumors.

PMID- 19771161
TI  - Solution structure and phylogenetics of Prod1, a member of the three-finger
      protein superfamily implicated in salamander limb regeneration.
AB  - BACKGROUND: Following the amputation of a limb, newts and salamanders have the
      capability to regenerate the lost tissues via a complex process that takes place
      at the site of injury. Initially these cells undergo dedifferentiation to a state
      competent to regenerate the missing limb structures. Crucially, dedifferentiated
      cells have memory of their level of origin along the proximodistal (PD) axis of
      the limb, a property known as positional identity. Notophthalmus viridescens
      Prod1 is a cell-surface molecule of the three-finger protein (TFP) superfamily
      involved in the specification of newt limb PD identity. The TFP superfamily is a
      highly diverse group of metazoan proteins that includes snake venom toxins,
      mammalian transmembrane receptors and miscellaneous signaling molecules.
      METHODOLOGY/PRINCIPAL FINDINGS: With the aim of identifying potential orthologs
      of Prod1, we have solved its 3D structure and compared it to other known TFPs
      using phylogenetic techniques. The analysis shows that TFP 3D structures group in
      different categories according to function. Prod1 clusters with other cell
      surface protein TFP domains including the complement regulator CD59 and the C
      terminal domain of urokinase-type plasminogen activator. To infer orthology, a
      structure-based multiple sequence alignment of representative TFP family members
      was built and analyzed by phylogenetic methods. Prod1 has been proposed to be the
      salamander CD59 but our analysis fails to support this association. Prod1 is not
      a good match for any of the TFP families present in mammals and this result was
      further supported by the identification of the putative orthologs of both CD59
      and N. viridescens Prod1 in sequence data for the salamander Ambystoma tigrinum.
      CONCLUSIONS/SIGNIFICANCE: The available data suggest that Prod1, and thereby its
      role in encoding PD identity, is restricted to salamanders. The lack of
      comparable limb-regenerative capability in other adult vertebrates could be
      correlated with the absence of the Prod1 gene.

PMID- 19771162
TI  - The human RNA polymerase II-associated factor 1 (hPaf1): a new regulator of cell
      cycle progression.
AB  - BACKGROUND: The human PAF (hPAF) complex is part of the RNA polymerase II
      transcription apparatus and regulates multiple steps in gene expression. Further,
      the yeast homolog of hPaf1 has a role in regulating the expression of a subset of
      genes involved in the cell-cycle. We therefore investigated the role of hPaf1
      during progression of the cell-cycle. METHODOLOGY/FINDINGS: Herein, we report
      that the expression of hPaf1, a subunit of the hPAF complex, increases with cell
      cycle progression and is regulated in a cell-cycle dependant manner. hPaf1
      specifically regulates a subclass of genes directly implicated in cell-cycle
      progression during G1/S, S/G2, and G2/M. In prophase, hPaf1 aligns in filament
      like structures, whereas in metaphase it is present within the pole forming a
      crown-like structure, surrounding the centrosomes. Moreover, hPaf1 is degraded
      during the metaphase to anaphase transition. In the nucleus, hPaf1 regulates the
      expression of cyclins A1, A2, D1, E1, B1, and Cdk1. In addition, expression of
      hPaf1 delays DNA replication but favors the G2/M transition, in part through
      microtubule assembly and mitotic spindle formation. CONCLUSION/SIGNIFICANCE: Our
      results identify hPaf1 and the hPAF complex as key regulators of cell-cycle
      progression. Mutation or loss of stoichiometry of at least one of the members may
      potentially lead to cancer development.

PMID- 19771163
TI  - Plasmacytoid dendritic cells capture and cross-present viral antigens from
      influenza-virus exposed cells.
AB  - Among the different subsets of dendritic cells (DC), plasmacytoid dendritic cells
      (PDC) play a unique role in secreting large amounts of type I interferons upon
      viral stimulation, but their efficiency as antigen-presenting cells has not been
      completely characterized. We show here, by flow cytometry, with human primary
      blood PDC and with a PDC cell line, that PDC display poor endocytic capacity for
      soluble or cellular antigens when compared to monocyte-derived myeloid DC.
      However, immature PDC efficiently take up cellular material from live influenza
      exposed cells, subsequently mature and cross-present viral antigens very
      efficiently to specific CD8+ T cells. Therefore, during viral infection PDC not
      only secrete immunomodulatory cytokines, but also recognize infected cells and
      function as antigen cross-presenting cells to trigger the anti-viral immune
      response.

PMID- 19771164
TI  - Latent cluster analysis of ALS phenotypes identifies prognostically differing
      groups.
AB  - BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a degenerative disease
      predominantly affecting motor neurons and manifesting as several different
      phenotypes. Whether these phenotypes correspond to different underlying disease
      processes is unknown. We used latent cluster analysis to identify groupings of
      clinical variables in an objective and unbiased way to improve phenotyping for
      clinical and research purposes. METHODS: Latent class cluster analysis was
      applied to a large database consisting of 1467 records of people with ALS, using
      discrete variables which can be readily determined at the first clinic
      appointment. The model was tested for clinical relevance by survival analysis of
      the phenotypic groupings using the Kaplan-Meier method. RESULTS: The best model
      generated five distinct phenotypic classes that strongly predicted survival
      (p<0.0001). Eight variables were used for the latent class analysis, but a good
      estimate of the classification could be obtained using just two variables: site
      of first symptoms (bulbar or limb) and time from symptom onset to diagnosis
      (p<0.00001). CONCLUSION: The five phenotypic classes identified using latent
      cluster analysis can predict prognosis. They could be used to stratify patients
      recruited into clinical trials and generating more homogeneous disease groups for
      genetic, proteomic and risk factor research.

PMID- 19771165
TI  - Compartmentalization of HIV-1 within the female genital tract is due to monotypic
      and low-diversity variants not distinct viral populations.
AB  - BACKGROUND: Compartmentalization of HIV-1 between the genital tract and blood was
      noted in half of 57 women included in 12 studies primarily using cell-free virus.
      To further understand differences between genital tract and blood viruses of
      women with chronic HIV-1 infection cell-free and cell-associated virus
      populations were sequenced from these tissues, reasoning that integrated viral
      DNA includes variants archived from earlier in infection, and provides a greater
      array of genotypes for comparisons. METHODOLOGY/PRINCIPAL FINDINGS: Multiple
      sequences from single-genome-amplification of HIV-1 RNA and DNA from the genital
      tract and blood of each woman were compared in a cross-sectional study. Maximum
      likelihood phylogenies were evaluated for evidence of compartmentalization using
      four statistical tests. Genital tract and blood HIV-1 appears compartmentalized
      in 7/13 women by >/=2 statistical analyses. These subjects' phylograms were
      characterized by low diversity genital-specific viral clades interspersed between
      clades containing both genital and blood sequences. Many of the genital-specific
      clades contained monotypic HIV-1 sequences. In 2/7 women, HIV-1 populations were
      significantly compartmentalized across all four statistical tests; both had low
      diversity genital tract-only clades. Collapsing monotypic variants into a single
      sequence diminished the prevalence and extent of compartmentalization. Viral
      sequences did not demonstrate tissue-specific signature amino acid residues,
      differential immune selection, or co-receptor usage. CONCLUSIONS/SIGNIFICANCE: In
      women with chronic HIV-1 infection multiple identical sequences suggest
      proliferation of HIV-1-infected cells, and low diversity tissue-specific
      phylogenetic clades are consistent with bursts of viral replication. These
      monotypic and tissue-specific viruses provide statistical support for
      compartmentalization of HIV-1 between the female genital tract and blood.
      However, the intermingling of these clades with clades comprised of both genital
      and blood sequences and the absence of tissue-specific genetic features suggests
      compartmentalization between blood and genital tract may be due to viral
      replication and proliferation of infected cells, and questions whether HIV-1 in
      the female genital tract is distinct from blood.

PMID- 19771166
TI  - In vivo turnover of tau and APP metabolites in the brains of wild-type and Tg2576
      mice: greater stability of sAPP in the beta-amyloid depositing mice.
AB  - The metabolism of the amyloid precursor protein (APP) and tau are central to the
      pathobiology of Alzheimer's disease (AD). We have examined the in vivo turnover
      of APP, secreted APP (sAPP), Abeta and tau in the wild-type and Tg2576 mouse
      brain using cycloheximide to block protein synthesis. In spite of overexpression
      of APP in the Tg2576 mouse, APP is rapidly degraded, similar to the rapid
      turnover of the endogenous protein in the wild-type mouse. sAPP is cleared from
      the brain more slowly, particularly in the Tg2576 model where the half-life of
      both the endogenous murine and transgene-derived human sAPP is nearly doubled
      compared to wild-type mice. The important Abeta degrading enzymes neprilysin and
      IDE were found to be highly stable in the brain, and soluble Abeta40 and Abeta42
      levels in both wild-type and Tg2576 mice rapidly declined following the depletion
      of APP. The cytoskeletal-associated protein tau was found to be highly stable in
      both wild-type and Tg2576 mice. Our findings unexpectedly show that of these
      various AD-relevant protein metabolites, sAPP turnover in the brain is the most
      different when comparing a wild-type mouse and a beta-amyloid depositing, APP
      overexpressing transgenic model. Given the neurotrophic roles attributed to sAPP,
      the enhanced stability of sAPP in the beta-amyloid depositing Tg2576 mice may
      represent a neuroprotective response.

PMID- 19771167
TI  - Melatonin promotes oligodendroglial maturation of injured white matter in
      neonatal rats.
AB  - OBJECTIVE: To investigate the effects of melatonin treatment in a rat model of
      white matter damage (WMD) in the developing brain. Additionally, we aim to
      delineate the cellular mechanisms of melatonin effect on the oligodendroglial
      cell lineage. METHODS: A unilateral ligation of the uterine artery in pregnant
      rat at the embryonic day 17 induces fetal hypoxia and subsequent growth
      restriction (GR) in neonatal pups. GR and control pups received a daily intra
      peritoneal injection of melatonin from birth to post-natal day (P) 3. RESULTS:
      Melatonin administration was associated with a dramatic decrease in microglial
      activation and astroglial reaction compared to untreated GR pups. At P14,
      melatonin prevented white matter myelination defects with an increased number of
      mature oligodendrocytes (APC-immunoreactive) in treated GR pups. Conversely,
      melatonin was not found to be associated with an increased density of total
      oligodendrocytes (Olig2-immunoreactive), suggesting that melatonin is able to
      promote oligodendrocyte maturation but not proliferation. These effects appear to
      be melatonin-receptor dependent and were reproduced in vitro. INTERPRETATION:
      These data suggest that melatonin has a strong protective effect on developing
      damaged white matter through decreased microglial activation and oligodendroglial
      maturation leading to a normalization of the myelination process. Consequently,
      melatonin should be a considered as an effective neuroprotective candidate not
      only in perinatal brain damage but also in inflammatory and demyelinating
      diseases observed in adults.

PMID- 19771168
TI  - Need for timely paediatric HIV treatment within primary health care in rural
      South Africa.
AB  - BACKGROUND: In areas where adult HIV prevalence has reached hyperendemic levels,
      many infants remain at risk of acquiring HIV infection. Timely access to care and
      treatment for HIV-infected infants and young children remains an important
      challenge. We explore the extent to which public sector roll-out has met the
      estimated need for paediatric treatment in a rural South African setting.
      METHODS: Local facility and population-based data were used to compare the number
      of HIV infected children accessing HAART before 2008, with estimates of those in
      need of treatment from a deterministic modeling approach. The impact of
      programmatic improvements on estimated numbers of children in need of treatment
      was assessed in sensitivity analyses. FINDINGS: In the primary health care
      programme of HIV treatment 346 children <16 years of age initiated HAART by 2008;
      245(70.8%) were aged 10 years or younger, and only 2(<1%) under one year of age.
      Deterministic modeling predicted 2,561 HIV infected children aged 10 or younger
      to be alive within the area, of whom at least 521(20.3%) would have required
      immediate treatment. Were extended PMTCT uptake to reach 100% coverage, the
      annual number of infected infants could be reduced by 49.2%. CONCLUSION: Despite
      progress in delivering decentralized HIV services to a rural sub-district in
      South Africa, substantial unmet need for treatment remains. In a local setting,
      very few children were initiated on treatment under 1 year of age and steps have
      now been taken to successfully improve early diagnosis and referral of infected
      infants.

PMID- 19771169
TI  - Screen for chemical modulators of autophagy reveals novel therapeutic inhibitors
      of mTORC1 signaling.
AB  - BACKGROUND: Mammalian target of rapamycin complex 1 (mTORC1) is a protein kinase
      that relays nutrient availability signals to control numerous cellular functions
      including autophagy, a process of cellular self-eating activated by nutrient
      depletion. Addressing the therapeutic potential of modulating mTORC1 signaling
      and autophagy in human disease requires active chemicals with pharmacologically
      desirable properties. METHODOLOGY/PRINCIPAL FINDINGS: Using an automated cell
      based assay, we screened a collection of >3,500 chemicals and identified three
      approved drugs (perhexiline, niclosamide, amiodarone) and one pharmacological
      reagent (rottlerin) capable of rapidly increasing autophagosome content.
      Biochemical assays showed that the four compounds stimulate autophagy and inhibit
      mTORC1 signaling in cells maintained in nutrient-rich conditions. The compounds
      did not inhibit mTORC2, which also contains mTOR as a catalytic subunit,
      suggesting that they do not inhibit mTOR catalytic activity but rather inhibit
      signaling to mTORC1. mTORC1 inhibition and autophagosome accumulation induced by
      perhexiline, niclosamide or rottlerin were rapidly reversed upon drug withdrawal
      whereas amiodarone inhibited mTORC1 essentially irreversibly. TSC2, a negative
      regulator of mTORC1, was required for inhibition of mTORC1 signaling by rottlerin
      but not for mTORC1 inhibition by perhexiline, niclosamide and amiodarone.
      Transient exposure of immortalized mouse embryo fibroblasts to these drugs was
      not toxic in nutrient-rich conditions but led to rapid cell death by apoptosis in
      starvation conditions, by a mechanism determined in large part by the tuberous
      sclerosis complex protein TSC2, an upstream regulator of mTORC1. By contrast,
      transient exposure to the mTORC1 inhibitor rapamycin caused essentially
      irreversible mTORC1 inhibition, sustained inhibition of cell growth and no
      selective cell killing in starvation. CONCLUSION/SIGNIFICANCE: The observation
      that drugs already approved for human use can reversibly inhibit mTORC1 and
      stimulate autophagy should greatly facilitate the preclinical and clinical
      testing of mTORC1 inhibition for indications such as tuberous sclerosis,
      diabetes, cardiovascular disease and cancer.

PMID- 19771170
TI  - Estrogen/estrogen receptor alpha signaling in mouse posterofrontal cranial suture
      fusion.
AB  - BACKGROUND: While premature suture fusion, or craniosynostosis, is a relatively
      common condition, the cause is often unknown. Estrogens are associated with
      growth plate fusion of endochondral bones. In the following study, we explore the
      previously unknown significance of estrogen/estrogen receptor signaling in
      cranial suture biology. METHODOLOGY/PRINCIPAL FINDINGS: Firstly, estrogen
      receptor (ER) expression was examined in physiologically fusing (posterofrontal)
      and patent (sagittal) mouse cranial sutures by quantitative RT-PCR. Next, the
      cranial suture phenotype of ER alpha and ER beta knockout (alphaERKO, betaERKO)
      mice was studied. Subsequently, mouse suture-derived mesenchymal cells (SMCs)
      were isolated; the effects of 17-beta estradiol or the estrogen antagonist
      Fulvestrant on gene expression, osteogenic and chondrogenic differentiation were
      examined in vitro. Finally, in vivo experiments were performed in which
      Fulvestrant was administered subcutaneously to the mouse calvaria. Results showed
      that increased ERalpha but not ERbeta transcript abundance temporally coincided
      with posterofrontal suture fusion. The alphaERKO but not betaERKO mouse exhibited
      delayed posterofrontal suture fusion. In vitro, addition of 17-beta estradiol
      enhanced both osteogenic and chondrogenic differentiation in suture-derived
      mesenchymal cells, effects reversible by Fulvestrant. Finally, in vivo
      application of Fulvestrant significantly diminished calvarial osteogenesis,
      inhibiting suture fusion. CONCLUSIONS/SIGNIFICANCE: Estrogen signaling through
      ERalpha but not ERbeta is associated with and necessary for normal mouse
      posterofrontal suture fusion. In vitro studies suggest that estrogens may play a
      role in osteoblast and/or chondrocyte differentiation within the cranial suture
      complex.

PMID- 19771171
TI  - Analysis of allogenicity of mesenchymal stem cells in engraftment and wound
      healing in mice.
AB  - Studies have shown that allogeneic (allo-) bone marrow derived mesenchymal stem
      cells (BM-MSCs) may enhance tissue repair/regeneration. However, recent studies
      suggest that immune rejection may occur to allo-MSCs leading to reduced
      engraftment. In this study, we compared allo-BM-MSCs with syngeneic BM-MSCs or
      allo-fibroblasts in engraftment and effect in wound healing. Equal numbers of GFP
      expressing allo-BM-MSCs, syngeneic BM-MSCs or allo-fibroblasts were implanted
      into excisional wounds in GFP-negative mice. Quantification of GFP-expressing
      cells in wounds at 7, 14 and 28 days indicated similar amounts of allogeneic or
      syngeneic BM-MSCs but significantly reduced amounts of allo-fibroblasts. With
      healing progression, decreasing amounts of allogeneic and syngeneic BM-MSCs were
      found in the wound; however, the reduction was more evident (2 fold) in allo
      fibroblasts. Similar effects in enhancing wound closure were found in allogeneic
      and syngeneic BM-MSCs but not in allo-fibroblasts. Histological analysis showed
      that allo-fibroblasts were largely confined to the injection sites while allo-BM
      MSCs had migrated into the entire wound. Quantification of inflammatory cells in
      wounds showed that allo-fibroblast- but not allo-BM-MSC-treated wounds had
      significantly increased CD45+ leukocytes, CD3+ lymphocytes and CD8+ T cells. Our
      study suggests that allogeneic BM-MSCs exhibit ignorable immunogenicity and are
      equally efficient as syngeneic BM-MSCs in engraftment and in enhancing wound
      healing.

PMID- 19771172
TI  - Interleukin-10 overexpression promotes Fas-ligand-dependent chronic macrophage
      mediated demyelinating polyneuropathy.
AB  - BACKGROUND: Demyelinating polyneuropathy is a debilitating, poorly understood
      disease that can exist in acute (Guillain-Barre syndrome) or chronic forms.
      Interleukin-10 (IL-10), although traditionally considered an anti-inflammatory
      cytokine, has also been implicated in promoting abnormal angiogenesis in the eye
      and in the pathobiology of autoimmune diseases such as lupus and
      encephalomyelitis. PRINCIPAL FINDINGS: Overexpression of IL-10 in a transgenic
      mouse model leads to macrophage-mediated demyelinating polyneuropathy. IL-10
      upregulates ICAM-1 within neural tissues, promoting massive macrophage influx,
      inflammation-induced demyelination, and subsequent loss of neural tissue
      resulting in muscle weakness and paralysis. The primary insult is to perineural
      myelin followed by secondary axonal loss. Infiltrating macrophages within the
      peripheral nerves demonstrate a highly pro-inflammatory signature. Macrophages
      are central players in the pathophysiology, as in vivo depletion of macrophages
      using clodronate liposomes reverses the phenotype, including progressive nerve
      loss and paralysis. Macrophage-mediate demyelination is dependent on Fas-ligand
      (FasL)-mediated Schwann cell death. SIGNIFICANCE: These findings mimic the human
      disease chronic idiopathic demyelinating polyneuropathy (CIDP) and may also
      promote further understanding of the pathobiology of related conditions such as
      acute idiopathic demyelinating polyneuropathy (AIDP) or Guillain-Barre syndrome.

PMID- 19771173
TI  - Economic analysis of pandemic influenza vaccination strategies in Singapore.
AB  - BACKGROUND: All influenza pandemic plans advocate pandemic vaccination. However,
      few studies have evaluated the cost-effectiveness of different vaccination
      strategies. This paper compares the economic outcomes of vaccination compared
      with treatment with antiviral agents alone, in Singapore. METHODOLOGY: We
      analyzed the economic outcomes of pandemic vaccination (immediate vaccination and
      vaccine stockpiling) compared with treatment-only in Singapore using a decision
      based model to perform cost-benefit and cost-effectiveness analyses. We also
      explored the annual insurance premium (willingness to pay) depending on the
      perceived risk of the next pandemic occurring. PRINCIPAL FINDINGS: The treatment
      only strategy resulted in 690 deaths, 13,950 hospitalization days, and economic
      cost of USD$497 million. For immediate vaccination, at vaccine effectiveness of
      >55%, vaccination was cost-beneficial over treatment-only. Vaccine stockpiling is
      not cost-effective in most scenarios even with 100% vaccine effectiveness. The
      annual insurance premium was highest with immediate vaccination, and was lower
      with increased duration to the next pandemic. The premium was also higher with
      higher vaccine effectiveness, attack rates, and case-fatality rates. Stockpiling
      with case-fatality rates of 0.4-0.6% would be cost-beneficial if vaccine
      effectiveness was >80%; while at case-fatality of >5% stockpiling would be cost
      beneficial even if vaccine effectiveness was 20%. High-risk sub-groups warrant
      higher premiums than low-risk sub-groups. CONCLUSIONS: The actual pandemic
      vaccine effectiveness and lead time is unknown. Vaccine strategy should be based
      on perception of severity. Immediate vaccination is most cost-effective, but
      requires vaccines to be available when required. Vaccine stockpiling as insurance
      against worst-case scenarios is also cost-effective. Research and development is
      therefore critical to develop and stockpile cheap, readily available effective
      vaccines.

PMID- 19771174
TI  - Gender-specific modulation of the response to arterial injury by soluble
      guanylate cyclase alpha1.
AB  - OBJECTIVE: Soluble guanylate cyclase (sGC), a heterodimer composed of alpha and
      beta subunits, synthesizes cGMP in response to nitric oxide (NO). NO modulates
      vascular tone and structure but the relative contributions of cGMP-dependent
      versus cGMP-independent mechanisms remain uncertain. We studied the response to
      vascular injury in male (M) and female (F) mice with targeted deletion of exon 6
      of the sGCalpha1 subunit (sGCalpha1(-/-)), resulting in a non-functional
      heterodimer. METHODS: We measured aortic cGMP levels and mRNA transcripts
      encoding sGC alpha1, alpha2, and beta1 subunits in wild type (WT) and sGCa1(-/-)
      mice. To study the response to vascular injury, BrdU-incorporation and neointima
      formation (maximum intima to media (I/M) ratio) were determined 5 and 28 days
      after carotid artery ligation, respectively. RESULTS: Aortic cGMP levels were 4
      fold higher in F than in M mice in both genotypes, and, within each gender, 4
      fold higher in WT than in sGCa1(-/-). In contrast, sGCalpha1, sGCalpha2, and
      sGCbeta1 mRNA expression did not differ between groups. 3H-thymidine
      incorporation in cultured sGCa1(-/-) smooth muscle cells (SMC) was 27%+/-12%
      lower than in WT SMC and BrdU-incorporation in carotid arteries 5 days after
      ligation was significantly less in sGCa1(-/-) M than in WT M. Neointima area and
      I/M 28 days after ligation were 65% and 62% lower in sGCa1(-/-) M than in WT M
      mice (p<0,05 for both) but were not different in F mice. CONCLUSION: Functional
      deletion of sGCa1 resulted in reduced cGMP levels in male sGCa1(-/-) mice and a
      gender-specific effect on the adaptive response to vascular injury.

PMID- 19771175
TI  - Genetic variants of the alpha-synuclein gene SNCA are associated with multiple
      system atrophy.
AB  - BACKGROUND: Multiple system atrophy (MSA) is a progressive neurodegenerative
      disorder characterized by parkinsonism, cerebellar ataxia and autonomic
      dysfunction. Pathogenic mechanisms remain obscure but the neuropathological
      hallmark is the presence of alpha-synuclein-immunoreactive glial cytoplasmic
      inclusions. Genetic variants of the alpha-synuclein gene, SNCA, are thus strong
      candidates for genetic association with MSA. One follow-up to a genome-wide
      association of Parkinson's disease has identified association of a SNP in SNCA
      with MSA. METHODOLOGY/FINDINGS: We evaluated 32 SNPs in the SNCA gene in a
      European population of 239 cases and 617 controls recruited as part of the
      Neuroprotection and Natural History in Parkinson Plus Syndromes (NNIPPS) study.
      We used 161 independently collected samples for replication. Two SNCA SNPs showed
      association with MSA: rs3822086 (P = 0.0044), and rs3775444 (P = 0.012), although
      only the first survived correction for multiple testing. In the MSA-C subgroup
      the association strengthened despite more than halving the number of cases:
      rs3822086 P = 0.0024, OR 2.153, (95% CI 1.3-3.6); rs3775444 P = 0.0017, OR 4.386
      (95% CI 1.6-11.7). A 7-SNP haplotype incorporating three SNPs either side of
      rs3822086 strengthened the association with MSA-C further (best haplotype, P =
      8.7 x 10(-4)). The association with rs3822086 was replicated in the independent
      samples (P = 0.035). CONCLUSIONS/SIGNIFICANCE: We report a genetic association
      between MSA and alpha-synuclein which has replicated in independent samples. The
      strongest association is with the cerebellar subtype of MSA. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT00211224.

PMID- 19771177
TI  - RNA unwinding by NS3 helicase: a statistical approach.
AB  - The study of double-stranded RNA unwinding by helicases is a problem of basic
      scientific interest. One such example is provided by studies on the hepatitis C
      virus (HCV) NS3 helicase using single molecule mechanical experiments. HCV
      currently infects nearly 3% of the world population and NS3 is a protein
      essential for viral genome replication. The objective of this study is to model
      the RNA unwinding mechanism based on previously published data and study its
      characteristics and their dependence on force, ATP and NS3 protein concentration.
      In this work, RNA unwinding by NS3 helicase is hypothesized to occur in a series
      of discrete steps and the steps themselves occurring in accordance with an
      underlying point process. A point process driven change point model is employed
      to model the RNA unwinding mechanism. The results are in large agreement with
      findings in previous studies. A gamma distribution based renewal process was
      found to model well the point process that drives the unwinding mechanism. The
      analysis suggests that the periods of constant extension observed during NS3
      activity can indeed be classified into pauses and subpauses and that each depend
      on the ATP concentration. The step size is independent of external factors and
      seems to have a median value of 11.37 base pairs. The steps themselves are
      composed of a number of substeps with an average of about 4 substeps per step and
      an average substep size of about 3.7 base pairs. An interesting finding pertains
      to the stepping velocity. Our analysis indicates that stepping velocity may be of
      two kinds- a low and a high velocity.

PMID- 19771176
TI  - The impact of antiretroviral therapy in a cohort of HIV infected patients going
      in and out of the San Francisco county jail.
AB  - BACKGROUND: Jails are an important venue of HIV care and a place for
      identification, treatment and referral for care. HIV infected inmates in the San
      Francisco County jail are offered antiretroviral treatment (ART), which many take
      only while in jail. We evaluated the effect of ART administration in a cohort of
      jail inmates going in and out of jail over a nine year period.
      METHODOLOGY/PRINCIPAL FINDINGS: In this retrospective study, we examined inmates
      with HIV going in and out of jail. Inmates were categorized by patterns of ART
      use: continuous ART - ART both in and out of jail, intermittent ART - ART only in
      jail; never on ART - eligible by national guidelines, but refused ART. CD4 and
      HIV viral load (VL) were compared over time in these groups. Over a 9 year
      period, 512 inmates were studied: 388 (76%) on intermittent ART, 79 (15%) on
      continuous ART and 45(9%) never-on ART. In a linear mixed model analysis, inmates
      on intermittent ART were 1.43; 95%CI (1.03, 1.99) times and those never on ART
      were 2.89; 95%CI (1.71, 4.87) times more likely to have higher VL than inmates on
      continuous ART. Furthermore, Inmates on intermittent ART and never-on ART lost
      1.60; 95%CI (1.06, 2.13) and 1.97; 95%CI (0.96, 3.00) more CD4 cells per month,
      respectively, compared to continuously treated inmates. The continuous ART
      inmates gained 0.67CD4 cells/month. CONCLUSIONS/SIGNIFICANCE: Continuous ART
      therapy in jail inmate's benefits CD4 cell counts and control of VL especially
      compared to those who never took ART. Although jail inmates on intermittent ART
      were more likely to lose CD4 cells and experience higher VL over time than those
      on continuous ART, CD4 cell loss was slower in these inmates as compared to
      inmates never on ART. Further studies are needed to evaluate whether or not
      intermittent ART provides some benefit in outcome if continuous ART is not
      possible or likely.

PMID- 19771178
TI  - TNFA and IL10 gene polymorphisms are not associated with periodontitis in
      Brazilians.
AB  - IL-10 and TNF-alpha are cytokines that have complex and opposing roles in the
      inflammatory responses. G/A polymorphisms at position -1082 of IL10 and -308 of
      TNFA genes have been reported to influence the expression of IL-10 and TNF-alpha,
      respectively. The aim of this study was to investigate the association between
      the IL10 (-1082) and TNFA (- 308) gene polymorphisms with different clinical
      forms or severity of periodontitis in a sample of Brazilian individuals. DNA was
      obtained from oral swabs of 165 Brazilian individuals, which were divided into
      three groups: individuals with chronic periodontitis, aggressive periodontitis
      and individuals without clinical evidence of periodontitis. Evaluation of IL10
      and TNFA polymorphisms was performed by RFLP analysis. Statistical analysis of
      data was performed using the Chi2 likelihood ratio and Fisher;s exact test. No
      significant differences in the genotype and allele distribution of either IL10 or
      TNFA were observed among individuals with different clinical forms or with
      different degrees of severity of periodontitis. Moreover, combined analysis of
      IL10 and TNFA polymorphisms did not show any association with periodontal status.
      As conclusion, the IL10 and TNFA gene promoter polymorphisms investigated are not
      associated with different clinical forms of periodontitis or with severity of the
      disease in the Brazilian population polymorphisms.

PMID- 19771179
TI  - Epstein-Barr-Virus-Infected CD15 (Lewis X)-Positive Hodgkin-Lymphoma-Like B Cells
      in Patients with Rheumatoid Arthritis.
AB  - Patients with rheumatoid arthritis (RA), especially those who are treated with
      methotrexate (MTX), might have an increased risk of Hodgkin lymphoma (HL), a
      malignancy that is associated with Epstein-Barr virus (EBV). Here we describe a
      monoclonal EBV-infected B-lymphoblastoid cell line (LCL) called TKS-1 that was
      established from cells that spontaneously converted from an MTX-treated RA
      patient. TKS-1 has properties similar to HL cells and it is distinctly different
      from control LCLs established from normal individuals. TKS-1 cells express the HL
      -associated surface markers CD15 and CD30 (Takei et al. 1989). Like Hodgkin Reed
      Sternberg (H-RS) cells of EBV-positive HL, TKS-1 cells express EBNA1 mRNA
      transcribed from the Qp promoter of the virus, whereas control LCLs use the Cp or
      Wp promoter to transcribe mRNA. TKS-1 cells can proliferate in an anchorage
      independent manner and possess a cloning efficiency comparable to that of the
      Burkitt lymphoma (BL) line Raji. In addition, two EBV-positive LCLs established
      by cocultivated CD34+ cells isolated from the bone marrow of patients with RA and
      peripheral blood B lymphocytes from a healthy EBV-seronegative individual also
      expressed CD15. These results indicate that EBV-infected B-lymphoblastoid cells
      from patients with RA tend to acquire properties similar to HL cells.

PMID- 19771180
TI  - Estimating dormant and active hematopoietic stem cell kinetics through extensive
      modeling of bromodeoxyuridine label-retaining cell dynamics.
AB  - Bone marrow hematopoietic stem cells (HSCs) are responsible for both lifelong
      daily maintenance of all blood cells and for repair after cell loss. Until
      recently the cellular mechanisms by which HSCs accomplish these two very
      different tasks remained an open question. Biological evidence has now been found
      for the existence of two related mouse HSC populations. First, a dormant HSC (d
      HSC) population which harbors the highest self-renewal potential of all blood
      cells but is only induced into active self-renewal in response to hematopoietic
      stress. And second, an active HSC (a-HSC) subset that by and large produces the
      progenitors and mature cells required for maintenance of day-to-day
      hematopoiesis. Here we present computational analyses further supporting the d
      HSC concept through extensive modeling of experimental DNA label-retaining cell
      (LRC) data. Our conclusion that the presence of a slowly dividing subpopulation
      of HSCs is the most likely explanation (amongst the various possible causes
      including stochastic cellular variation) of the observed long term
      Bromodeoxyuridine (BrdU) retention, is confirmed by the deterministic and
      stochastic models presented here. Moreover, modeling both HSC BrdU uptake and
      dilution in three stages and careful treatment of the BrdU detection sensitivity
      permitted improved estimates of HSC turnover rates. This analysis predicts that d
      HSCs cycle about once every 149-193 days and a-HSCs about once every 28-36 days.
      We further predict that, using LRC assays, a 75%-92.5% purification of d-HSCs can
      be achieved after 59-130 days of chase. Interestingly, the d-HSC proportion is
      now estimated to be around 30-45% of total HSCs - more than twice that of our
      previous estimate.

PMID- 19771181
TI  - Simvastatin induces apoptosis of fibroblast-like synoviocytes.
AB  - BACKGROUND: Statins (3-Hydroxy-3-methylglutaryl-CoA reductase inhibitors) exert
      favorable effects on lipoprotein metabolism, but appeared to possess anti
      inflammatory properties among others, as suggested by their ability to inhibit
      collagen-induced arthritis in mice. Their activity in fibroblast-like synovial
      cells (FLS) has not yet been studied. OBJECTIVES: To evaluate the effect of
      varying doses of simvastatin on apoptosis of FLS. METHODS: Synovial tissue,
      obtained during total knee replacement due to osteoarthritis, was cut into small
      pieces and cultured in Petri dishes with test materials, as previously described.
      FLS were incubated for 48 hours with 1 mumol/ml, 5 mumol/ ml, 15 mumol/ml and 50
      mumol/ml of simvastatin. Following incubation, apoptosis was analyzed by two
      dimensional flow cytometry (FACS) using annexin V/PI staining according to the
      manufacturer's instructions. RESULTS: Different concentrations of simvastatin
      induced apoptosis of FLS. The level proportion of apoptotic cells of resting or
      activated with lipopolysaccharide (LPS; 3 mug/ml) FLS, not treated with
      simvastatin, was 21%. At 48 hours, the rate of apoptosis of activated
      fibroblasts, incubated with 1 mumol/ml, 5 mumol/ml, 15 and 50 mumol/ml was 22%,
      32%, 48% and 41% respectively. Synovial cell viability evaluated by tetrazolium
      salt XXT was unaffected by the simvastatin concentration used. CONCLUSION:
      Varying concentrations of simvastatin induce apoptosis of activated fibroblast
      like synoviocytes, suggesting another possible mechanism of anti-inflammatory
      effects of statins in inflammatory conditions.

PMID- 19771182
TI  - "Evidence-based diagnosis and treatment of the painful sacroiliac joint" laslett
      m. J man manip 2008:16:142-152.

PMID- 19771183
TI  - Blue cross blue shield of Minnesota: missing the forest for the trees.

PMID- 19771184
TI  - A founding father of manual therapy has passed away.

PMID- 19771185
TI  - Clinimetrics Corner: The Minimal Clinically Important Change Score (MCID): A
      Necessary Pretense.
AB  - Minimal clinically important differences (MCID) are patient derived scores that
      reflect changes in a clinical intervention that are meaningful for the patient.
      At present, there are a number of different methods to obtain an MCID, as there a
      number of different factors that can influence the MCID value. This clinimetric
      corner outlines the hidden challenges associated with identifying a viable MCID
      and possible suggestions to improve the future development of these single
      scores.

PMID- 19771186
TI  - A morphological comparison of the human lumbar multifidus by chemical dissection.
AB  - This anatomical study describes the morphology of the human lumbar multifidus
      muscle through gross and chemical dissection of fresh cadavers. Previous
      morphological descriptions were analyzed with regard to fascicular divisions and
      cleavage planes. Gross dissection was performed on the lumbar multifidus of four
      fresh adult human cadavers and four preserved cadavers. Gradual chemical
      dissection using nitric or formic acid was used for connective tissue digestion
      to enhance the documentation of muscle fiber direction. Results revealed four
      distinct layers of the lumbar multifidus separated by cleavage planes. The
      superficial layer was more extensive than previously described with bony
      attachments at both the origin and insertion at several vertebral levels. The
      attachments of the second through fourth layers differed in that distinct
      cleavage planes between the various fascicles were not found with chemical
      dissection. The lumbar multifidus has a multipennate fiber arrangement, and the
      fascicles between the various layers inter-attach. Inter-fascicle attachment
      differs with the description by Macintosh et al of distinct cleavage planes
      between and within the fascicles of each layer. Accurate anatomical knowledge of
      the fascicles of the lumbar multifidus is integral for defining the actions of
      this complex lumbar muscle. This study supports the clinical belief that the
      multifidus has a significant role in control and stabilization of the lumbar
      spine in multiple planes of action. The multipennate arrangement of this muscle
      with fascicular inter-attachment supports the clinical premise that the
      multifidus is activated in a variety of positions and can potentially produce and
      mediate intersegmental mobility and provide proprioception.

PMID- 19771187
TI  - The association of nutritional status and gender with cross-sectional area of the
      multifidus muscle in establishing normative data.
AB  - Despite recognized evidence for the importance of the multifidus muscle in
      stabilizing the lumbar spine, identifying subjects at risk for injury and
      subsequent loss of intrinsic spinal stabilization remains difficult. Previous
      research has failed to associate multifidus muscle size and height, weight, or
      body mass index (BMI). The purpose of this study was to begin to establish
      normative data for the multifidus muscle cross-sectional area (CSA) at the L5
      level and to identify factors associated with size. Twenty-five participants (17
      female), with a mean age of 32.5 (SD 11.6) years without history of LBP were
      considered for inclusion. Participants' height and weight were recorded and BMI
      calculated. Ultrasound imaging was used to obtain a CSA in cm(2) of the subjects'
      multifidus muscles at the L5 level bilaterally; testing was done by two trained
      testers. Prior to testing, intra- and inter-tester reliability were determined.
      Percent body fat was determined using a three-site skinfold caliper measurement,
      also using two trained testers. Mean BMI was 24.18 and mean body fat (%) was
      22.88 for all participants. As expected, age and BMI were moderately correlated.
      Left and right multifidus muscle CSA were highly correlated (r = 0.92, p <
      0.001). The mixed model ANOVA indicated a significant main effect for gender as
      males exhibited larger CSA than females. Participants without history of low back
      pain present with symmetrical multifidus muscle CSA at the L5 level. Clear gender
      differences in CSA show that males tend to have larger multifidus muscles at the
      L5 level, indicating a need to establish gender-specific norms for clinicians
      examining the L5 multifidus muscle.

PMID- 19771188
TI  - 2008 AAOMPT John McM. Mennell Service Award Acceptance Speech.

PMID- 19771189
TI  - Trample the weak, hurdle the dead: the tribulations of integrating research into
      clinical practice.

PMID- 19771190
TI  - Spinal manipulative therapy for acute low back pain: a clinical perspective.
AB  - Low back pain (LBP) is an extremely common cause of pain and disability. While
      many treatments for acute LBP exist, one of the most widely used, but also most
      controversial, is spinal manipulative therapy (SMT). This therapy includes both
      high-velocity manipulative techniques and low-velocity mobilization techniques.
      The literature regarding the use of SMT is often conflicting, which explains the
      difference in recommendations regarding SMT in international LBP guidelines. The
      lack of a clear tissue diagnosis in the majority of patients with LBP combined
      with the unknown mechanism of action of SMT adds to the difficulty for clinicians
      in providing SMT in a logical and effective manner. Despite these limitations,
      the existing literature does provide some assistance to clinicians on when to
      provide SMT and how to provide it in an optimal way. This review aims to
      summarize the key research literature investigating SMT in LBP in order to help
      clinicians make informed decisions about the use of SMT for their patients with
      acute LBP.

PMID- 19771191
TI  - Invited commentary.

PMID- 19771192
TI  - Invited commentary.

PMID- 19771193
TI  - Reliability of joint mobility and pain assessment of the thoracic spine and rib
      cage in asymptomatic individuals.
AB  - Despite the importance of correctly diagnosing a spinal dysfunction, limited
      research exists related to physical therapists' ability to reliably identify a
      joint exhibiting signs of dysfunction. The purpose of this investigation was to
      determine the inter- and intra-examiner reliability of a thoracic spine and rib
      cage joint mobility and pain assessment between two experienced manipulative
      physical therapists. Nine healthy subjects (3 male, 6 female; ages 23-35) without
      history of mid- or low back pain participated. Posterior-to-anterior pressures
      were applied to the thoracic spine and rib articulations with anterior-to
      posterior pressures applied to the costosternal joints of each subject by two
      examiners to evaluate joint mobility and pain provocation. Both examiners
      assessed all subjects twice and were blinded to subject identity. Kappa
      statistics were calculated using a strict and expanded definition of agreement to
      determine the between- and within-examiner reliability for each outcome. Intra
      examiner reliability of joint mobility assessment ranged from slight to fair
      based on the strict agreement but improved to good when findings were compared
      across +/- 1 spinal/rib level. Pain provocation reliability increased to very
      good under the expanded agreement; however, this finding should be viewed with
      caution due to limited pain prevalence in the subject sample. Selected clinical
      prediction rules, applied to the care of individuals with back pain, characterize
      the patient's regional mobility simply as hypomobile, normal, or hypermobile;
      consequently, we feel the results of an expanded definition of agreement may be
      more appropriate for clinic practice. Further research is needed to determine the
      reliability in individuals with thoracic spine and rib cage symptoms.

PMID- 19771194
TI  - Multimodal management of mechanical neck pain using a treatment based
      classification system.
AB  - THE PURPOSE OF THIS CASE STUDY WAS TWOFOLD: 1) to illustrate the use of a
      treatment-based classification (TBC) system to direct the early intervention of a
      patient with mechanical neck pain, and 2) to show the progression of this patient
      with multimodal-modal intervention. The patient exhibited axial neck pain with
      referral into her upper extremity. Her pain peripheralized with cervical range of
      motion and centralized with joint mobilization placing her primarily in the
      centralization category. Her poor posture and associated muscle weakness along
      with the chronicity of symptoms placed her secondarily into the exercise and
      conditioning group resulting in a multi-modal treatment as the patient
      progressed. Although the design of this case report prevents wide applicability,
      this study does illustrate the effective use of the TBC system for the cervical
      spine as captured by accepted outcomes measures.

PMID- 19771195
TI  - A systematic review of the effectiveness of manipulative therapy in treating
      lateral epicondylalgia.
AB  - Lateral epicondylalgia is a commonly encountered musculoskeletal complaint.
      Currently, there is no agreement regarding the exact underlying pathoanatomical
      cause or the most effective management strategy. Various forms of joint
      manipulation have been recommended as treatment. The purpose of this study was to
      systematically review available literature regarding the effectiveness of
      manipulation in treating lateral epicondylalgia. A comprehensive search of
      Medline, CINAHL, Health Source, SPORTDiscus, and the Physiotherapy Evidence
      Database ending in November 2007 was conducted. Thirteen studies, both randomized
      and non-randomized clinical trials, met inclusion criteria. Articles were
      assessed for quality by one reviewer using the 10-point PEDro scale. Quality
      scores ranged from 1-8 with a mean score of 5.15 +/- 1.85. This score represented
      fair quality overall; however, trends indicated the presence of consistent
      methodological flaws. Specifically, no study achieved successful blinding of the
      patient or treating therapist, and less than 50% used a blinded outcome assessor.
      Additionally, studies varied significantly in terms of outcome measures, follow
      up, and comparison treatments, thus making comparing results across studies
      difficult. Results of this review support the use of Mulligan's mobilization with
      movement in providing immediate, short-, and long-term benefits. In addition,
      positive results were demonstrated with manipulative therapy directed at the
      cervical spine, although data regarding long-term effects were limited.
      Currently, limited evidence exists to support a synthesis of any particular
      technique whether directed at the elbow or cervical spine. Overall, this review
      identified the need for further high-quality studies using larger sample sizes,
      valid functional outcome measures, and longer follow-up periods.

PMID- 19771196
TI  - Comparison of manual therapy techniques with therapeutic exercise in the
      treatment of shoulder impingement: a randomized controlled pilot clinical trial.
AB  - The purpose of this double-blind, randomized controlled pilot study was to
      compare the effectiveness of four physical therapy interventions in the treatment
      of primary shoulder impingement syndrome: 1) supervised exercise only, 2)
      supervised exercise with glenohumeral mobilizations, 3) supervised exercise with
      a mobilization-with-movement (MWM) technique, or 4) a control group receiving
      only physician advice. Thirty-three subjects diagnosed with primary shoulder
      impingement were randomly assigned to one of these four groups. Main outcome
      measures included 24-hour pain (VAS), pain with the Neer and Hawkins-Kennedy
      tests, shoulder active range of motion (AROM), and shoulder function (SPADI).
      Repeated-measures analyses indicated significant decreases in pain, improved
      function, and increases in AROM. Univariate analyses on the percentage of change
      from pre- to post-treatment for each dependent variable found no statistically
      significant differences (P<0.05) between the four groups. Although not
      significant, the MWM and mobilization groups had a higher percentage of change
      from pre- to post-treatment on all three pain measures (VAS, Neer, Hawkins
      Kennedy). The three intervention groups had a higher percentage of change on the
      SPADI. The MWM group had the highest percentage of change in AROM, and the
      mobilization group had the lowest. This pilot study suggests that performing
      glenohumeral mobilizations and MWM in combination with a supervised exercise
      program may result in a greater decrease in pain and improved function although
      studies with larger samples and discriminant sampling methods are needed.

PMID- 19771197
TI  - The comparative prognostic value of directional preference and centralization: a
      useful tool for front-line clinicians?
AB  - A large number of prognostic factors have been associated with recovery from an
      episode of back pain, and much emphasis has been placed on psychosocial
      prognostic factors. The large number of prognostic factors and the lack of
      comparative analysis of different factors make use of these difficult in clinical
      practice. The aim of this study was to evaluate the comparative usefulness of a
      range of factors to predict outcome using data from a randomized controlled trial
      (RCT) in which 312 patients with sub-acute to chronic back pain received a
      mechanical evaluation and were sub-grouped based on the presence or absence of
      directional preference (DP). Patients were then randomized to treatment that was
      matched or unmatched to that DP. Patients with a minimal reduction of 30% in
      Roland-Morris Disability Questionnaire (RMDQ) score were defined as the good
      outcome group. Seventeen baseline variables were entered into a step-wise
      logistic regression analysis for the ability to predict a good outcome. Of the
      patients, 84 met the good outcome criteria and had a mean RMDQ decrease of 58.2%
      (9.8 points) in 4 visits. Leg pain, work status, depression, pain location,
      chronicity, and treatment assignment were significant predictors of outcome in
      univariate analysis. Only leg bothersomeness rating and treatment assignment
      survived multivariate analysis. Subjects with DP/centralization who received
      matched treatment had a 7.8 times greater likelihood of a good outcome. Matching
      patients to their DP is a stronger predictor of outcome than a range of other
      biopsychosocial factors.

PMID- 19771198
TI  - Vector-based siRNA delivery strategies for high-throughput screening of novel
      target genes.
AB  - Application of siRNA in high-throughput fashion is still in its early phase
      although the principle has been established for three years. In this review, we
      outline the different vector-based siRNA delivery platforms as well as resources
      that are becoming available for high-throughput applications, and some initial
      outcomes of vector siRNA high-throughput screening efforts using vector encoded
      siRNA. It is expected that further improvement of the siRNA technology and
      availability of the siRNA resources will help to materialize the potential of
      siRNA for functional genomics and drug target validation.

PMID- 19771199
TI  - The RISC component VIG is a target for dsRNA-independent protein kinase activity
      in Drosophila S2 cells.
AB  - RNA interference (RNAi) is mediated by a multicomponent RNA-induced silencing
      complex (RISC). Here we examine the phosphorylation state of three Drosophila
      RISC-associated proteins, VIG, R2D2 and a truncated form of Argonaute2 devoid of
      the nonconserved N-terminal glutamine-rich domain. We show that of the three
      studied proteins, only VIG is phosphorylated in cultured Drosophila cells. We
      also demonstrate that the phosphorylation state of VIG remains unchanged after
      cell transfection with exogenous dsRNA. A sequence similarity search revealed
      that VIG shares significant similarity with the human phosphoprotein Ki-1/57, a
      known in vivo substrate for protein kinase C (PKC). In vitro kinase assays
      followed by tryptic phosphopeptide mapping showed that PKC could efficiently
      phosphorylate VIG on multiple sites, suggesting PKC as a candidate kinase for VIG
      phosphorylation in vivo. Taken together, our results identify the RISC component
      VIG as a novel kinase substrate in cultured Drosophila cells and suggest a
      possible involvement of PKC in its phosphorylation.

PMID- 19771200
TI  - Mechanisms of RNAi: mRNA cleavage fragments may indicate stalled RISC.
AB  - The molecular mechanism of RNA interference (RNAi) is under intense
      investigation. We previously demonstrated the existence of inactive siRNAs and
      also of mRNA cleavage in vivo in human cells. Here it is shown that some siRNAs
      with low activity leave mRNA cleavage fragments while an siRNA with higher
      activity does not. The pattern is consistent with both short-term (4-24 hours)
      and long-term (1-4 days) time-series. Analysis of the putative 3' mRNA cleavage
      product showed high GC content immediately after the cleavage point. The cleavage
      fragments might indicate a stalled or slowed RNAi cleavage complex - possibly in
      the RISC enzyme restoration phase - and thus constitute a novel explanation for
      the existence of inactive siRNAs.

PMID- 19771201
TI  - Selective cleavage of AChR cRNAs harbouring mutations underlying the slow channel
      myasthenic syndrome by hammerhead ribozymes.
AB  - Slow channel congenital myasthenic syndrome (SCCMS) is a dominant disorder caused
      by missense mutations in muscle acetylcholine receptors (AChR). Expression from
      mutant alleles causes prolonged AChR ion-channel activations. This 'gain of
      function' results in excitotoxic damage due to excess entry of calcium ions that
      manifests as an endplate myopathy. The biology of SCCMS provides a model system
      to investigate the potential of catalytic nucleic acids for therapy in dominantly
      inherited disorders involving single missense mutations. Hammerhead ribozymes can
      catalytically cleave RNA transcripts in a sequence-specific manner. We designed
      hammerhead ribozymes to target transcripts from four SCCMS mutations, alphaT254I,
      alphaS226F, alphaS269I and epsilonL221F. Ribozymes were incubated with cRNA
      transcripts encoding wild type and mutant AChR subunits. The ribozymes
      efficiently cleaved the mutant allele cRNA transcripts but left the wild type
      cRNA intact. Cleavage efficiency was optimised for alphaS226F. We were able to
      demonstrate robust catalytic activity under simulated physiological conditions
      and at high Ca(2+) concentrations, which is likely to be accumulated at the
      endplate region of the SCCMS patient muscles. These results demonstrate the
      potential for gene therapy applications of ribozymes to specifically down
      regulate expression of mutant alleles in dominantly inherited disorders.

PMID- 19771202
TI  - Selective DNAzyme-mediated cleavage of AChR mutant transcripts by targeting the
      mutation site or through mismatches in the binding arm.
AB  - Many dominantly inherited disorders are caused by missense amino acid
      substitutions resulting from a single nucleotide exchange in the encoding gene.
      For these disorders, where proteins expressed from the mutant alleles are often
      pathogenic and present throughout life, gene silencing, through intervention at
      the mRNA level, holds promise as a therapeutic approach. We have used mutations
      that underlie the slow channel congenital myasthenic syndrome (SCCMS) as a model
      system to study allele-specific gene silencing of RNA transcripts by DNAzymes. We
      tested the ability of DNAzymes to give allele-specific cleavage for i) mutations
      that create cleavage sites, and ii) mutations located close to a DNAzyme cleavage
      site that create a potential mismatch in the binding arms. For both we
      demonstrate selective cleavage of mutant transcripts under simulated
      physiological conditions. For DNAzymes with binding arm mismatches the degree of
      selectivity for mutant over wild type may be enhanced by optimising the mismatch
      position as well as the binding arm length. The optimal sites for mismatches are
      1.1 and 1.2 in arm I, and 16.2 in arm II. Asymmetric binding arm DNAzymes with a
      shorter arm I are more discriminative. Our results show it should be possible to
      apply DNAzyme-mediated cleavage of mutant alleles even when the mutant does not
      itself create a putative cleavage site. This therapeutic approach may be well
      suited to dominantly inherited disorders such as SCCMS, where loss of some wild
      type transcripts is unlikely to have pathogenic consequences.

PMID- 19771203
TI  - Design and application of a versatile expression vector for RNAi in mammalian
      cells.
AB  - Here we report a versatile mammalian expression vector called pRIGHT11 for
      production of small interfering RNA (siRNA) in cells. This vector uses opposing
      eukaryotic RNA polymerase III promoters U6 and H1 to drive the expression of
      short siRNA. We have demonstrated the effectiveness of pRIGHT11-generated siRNA
      in sequence-specific inhibition of transfected reporter genes and endogenous
      genes. Furthermore, this retrovirus-based vector can carry a random library of
      siRNA, and thus can be applied to rapid screening of novel genes involved in
      specific cellular responses.

PMID- 19771205
TI  - RNA interference: Perspectives and caveats.

PMID- 19771204
TI  - PCR-based expression analysis and identification of microRNAs.
AB  - microRNAs (miRNAs) are small RNAs that regulate translation and hence control a
      variety of cellular processes in metazoans. The quantitation and identification
      of miRNAs has been hampered by their small size and low abundance. Here we
      describe two robust PCR-based assays of miRNA expression based on the original
      cloning strategy. The non-quantitative PCR method allows detection and
      identification of miRNAs and we utilise this method in the discovery of a new
      miRNA (miR-532) in retinoic acid differentiated P19 cells. The second and
      quantitative method (QM-RT-PCR) is simple and accurate, and uses commonly
      available technology. Of particular interest is the specificity of this PCR-based
      technology compared to hybridisation-based methods including arrays and northern
      blotting. Here we have shown that a single base pair mismatch in the priming
      sequence results in a two order of magnitude reduction in the amplification of
      let-7f. These streamlined methods will complement previously described methods
      and will facilitate analysis of miRNA expression in rare cell populations where
      the amount of RNA is limited.

PMID- 19771206
TI  - A novel approach for inhibition of HIV-1 by RNA interference: counteracting viral
      escape with a second generation of siRNAs.
AB  - RNA interference (RNAi) is an evolutionary conserved gene silencing mechanism in
      which small interfering RNA (siRNA) mediates the sequence specific degradation of
      mRNA. The recent discovery that exogenously delivered siRNA can trigger RNAi in
      mammalian cells raises the possibility to use this technology as a therapeutic
      tool against pathogenic viruses. Indeed, it has been shown that siRNAs can be
      used effectively to inhibit virus replication. The focus of this review is on RNA
      interference strategies against HIV-1 and how this new technology may be
      developed into a new successful therapy. One of the hallmarks of RNAi, its
      sequence specificity, also presents a way out for the virus, as single nucleotide
      substitutions in the target region can abolish the suppression. Strategies to
      prevent the emergence of resistant viruses have been suggested and involve the
      targeting of conserved sequences and the simultaneous use of multiple siRNAs,
      similar to current highly active antiretroviral therapy. We present an additional
      strategy aimed at preventing viral escape by using a second generation of siRNAs
      that recognize the mutated target sites.

PMID- 19771207
TI  - Prolonged transcriptional silencing and CpG methylation induced by siRNAs
      targeted to the HIV-1 promoter region.
AB  - In addition to the degradation of homologous RNAs through the RNA interference
      (RNAi) pathway, small interfering RNAs (siRNAs) can in some systems induce
      cytosine methylation and transcriptional silencing of homologous promoters.
      Targeting of HIV-1 by RNAi results in transient suppression of the virus through
      degradation of viral transcripts. In an effort to prolong the suppressive effect
      of siRNAs on productive HIV-1 infection, we targeted conserved tandem NF-kappaB
      binding motifs in the viral LTR. A 21-nucleotide-RNA duplex induced marked and
      durable (at least 30 days) suppression of productive HIV-1 infection in
      chronically infected Magic-5 cells. This suppression is associated with CpG
      methylation within the 5'LTR and marked reduction of HIV-1 transcription in
      nuclear run-on assays. We then assessed three additional siRNAs targeting other
      sites within the HIV-1 promoter region. These siRNAs suppressed HIV-1 infection
      to different extents and the degree of suppression correlated with the extent of
      de novo methylation of CpG motifs within the HIV-1 promoter region. These
      findings indicate that HIV-1 can be silenced by an RNA-directed mechanism that
      suppresses transcription and induces CpG methylation. In addition to providing
      evidence that this RNA-directed DNA methylation is active in mammalian cells,
      this is the first report of prolonged suppression of HIV-1 infection induced by
      siRNA.

PMID- 19771208
TI  - RNAi induced in mammalian and Drosophila cells via transfection of dimers and
      trimers of small interfering RNA.
AB  - Twenty one base pair long small interfering RNAs (siRNAs) are widely in use in
      mammalian RNAi experiments. The present study assesses the capability of 43 and
      63bp dsRNAs with two 2nt long 3'-overhangs to induce RNAi in mammalian and
      Drosophila cells. Human Dicer was found to cleave these dsRNAs from their ends to
      generate two or three monomeric siRNA units, each 21-22bp in length. When, in
      43bp dsRNA, there was present a highly-effective siRNA sequence in frame with
      respect to the Dicer digestion, considerably high RNAi activity was noted to be
      induced in mouse embryonic stem E14TG2a, human HeLa, Chinese hamster CHO-K1 or
      Drosophila S2 cells. In contrast, RNAi depending on 63bp dsRNA, containing a
      highly effective siRNA sequence in frame with respect to Dicer digestion, varied
      considerably depending on cell lines used. While there was no appreciable RNAi in
      HeLa cells associated with relatively strong interferon response, a significant
      level of RNAi was noted in E14TG2a, CHO-K1 and S2 cells, in all of which
      interferon response induction was but slight, if at all. It would thus follow
      that siRNA oligomers with sequence of a highly functional siRNA monomer unit in
      frame with respect to dicer digestion should serve as a good RNAi agent in
      Drosophila and certain mammalian cells.

PMID- 19771209
TI  - Design of efficient DNAzymes against muscle AChR alpha-subunit cRNA in vitro and
      in HEK 293 cells.
AB  - DNAzymes are catalytic DNA which bind to target RNA by complementary sequence
      arms on a Watson-Crick basis and cleave RNA at specific sites. Potential
      therapeutic applications require DNAzymes that can efficiently cleave their
      target. Here we investigate factors affecting DNAzyme cleavage efficacy against
      the muscle acetylcholine receptor (AChR) alpha-subunit. The 10-23 DNAzymes cleave
      at Y-R nucleotide motifs, where R is A or G, and Y is U or C. Targeting a series
      of sites within different regions of the full-coding length cRNA under simulated
      physiological conditions found that the most efficient motifs for cleavage were
      in the hierarchy: GU >/= AU > GC >>> AC. This order is consistent with the
      kinetic analysis of short synthetic RNA substrates that have the same binding
      arms but different cleavage sites. DNAzymes with longer symmetric binding arms
      were more efficient than those with shorter arms, while asymmetric DNAzymes with
      a longer arm I were also more efficient, suggesting a dominant role for arm I in
      determining cleavage activity. Modification of one DNAzyme by inverted thymidine
      (iT) or locked nucleic acids (LNA) showed the LNA-modified DNAzyme gave efficient
      silencing of AChR expression in HEK 293 cells. Our data demonstrate the
      usefulness of screening in vitro for an efficient DNAzyme prior to cellular
      applications.

PMID- 19771210
TI  - Frog Prince transposon-based RNAi vectors mediate efficient gene knockdown in
      human cells.
AB  - We have developed a stable RNA interference (RNAi) delivery system that is based
      on the Frog Prince transposable element. This plasmid-based vector system
      combines the gene silencing capabilities of H1 polymerase III promoter-driven
      short hairpin RNAs (shRNA) with the advantages of stable and efficient genomic
      integration of the shRNA cassette mediated by transposition. We show that the
      Frog Prince-based shRNA expressing system can efficiently knock down the
      expression of both exogenous as well as endogenous genes in human cells.
      Furthermore, we use the Frog Prince-based system to study the effect of knockdown
      of the DNA repair factor Ku70 on transposition of the Sleeping Beauty transposon.
      Transposon-mediated genomic integration ensures that the shRNA expression
      cassette and a selectable marker gene within the transposon remain intact and
      physically linked. We demonstrate that a major advantage of our vector system
      over plasmid-based shRNA delivery is both its enhanced frequency of intact
      genomic integration as well as higher target suppression in transgenic human
      cells. Due to its simplicity and effectiveness, transposon-based RNAi is an
      emerging tool to facilitate analysis of gene function through the establishment
      of stable loss-of-function cell lines.

PMID- 19771211
TI  - P-bodies and RNAi: The missing link?

PMID- 19771212
TI  - Designer siRNAs to overcome the challenges from the RNAi pathway.
AB  - Small interfering RNA (siRNA)-based technology is playing a pivotal role in
      understanding gene function. Huge siRNA libraries coupled to high-content
      screening are being applied to decipher molecular circuitries, as well as to
      identify novel therapeutic targets. Further, the technology is finding its way
      towards therapeutic applications. In the midst of all this excitement, the siRNA
      technology is faced with challenges, arising mostly from siRNAs being a nucleic
      acid molecule, and also from the baggage it inherits from the RNA interference
      (RNAi) pathway, which is critical to the function of siRNAs.

PMID- 19771213
TI  - Manipulating and enhancing the RNAi response.
AB  - The phenomenon that is known as RNA mediated interference (RNAi) was first
      observed in the nematode C. elegans. The application of RNAi has now been widely
      disseminated and the mechanisms underlying the pathway have been uncovered using
      both genetics and biochemistry. In the worm, it has been demonstrated that RNAi
      is easily adapted to high throughput analysis and screening protocols. Hence,
      given the availability of whole genome sequences, RNAi has been used extensively
      as a tool for annotating gene function. Genetic screens performed with C. elegans
      have also led to the identification of genes that are essential for RNAi or that
      modulate the RNAi process. The identification of such genes has made it possible
      to manipulate and enhance the RNAi response. Moreover, many of the genes
      identified in C. elegans have been conserved in other organisms. Thus,
      opportunities are available for researchers to take advantage of the insights
      gained from the worm and apply them to their own systems in order to improve the
      efficiency and potency of the RNAi response.

PMID- 19771214
TI  - In ovo RNAi opens new possibilities for temporal and spatial control of gene
      silencing during development of the vertebrate nervous system.
AB  - Loss-of-function approaches are important tools for functional gene analysis. Due
      to the availability of sophisticated methods to manipulate gene expression in
      embryonic stem cells that can be used to generate mutant mice, the mouse is by
      far the most important vertebrate model organism for basic and applied biomedical
      research. Unfortunately, the available methods do not allow for precise temporal
      and spatial control of gene silencing during embryonic development limiting the
      usefulness of the mouse for developmental studies. Due to their easy
      accessibility chicken embryos have been one of the preferred model organisms for
      developmental studies. Their disadvantage, the lack of genetic tools, could be
      overcome by the development of in ovo RNAi (in ovo RNA interference), a method
      that allows for temporal and spatial control of gene silencing in vivo.

PMID- 19771216
TI  - Long-term transgene expression and inhibition of HIV-1 replication by a Cre/loxP
      EBNA-1/oriP HIV-1-dependent ribozyme vector: Applications for HIV-1 gene therapy.
AB  - The cleavage of target mRNA by ribozymes is being exploited as a means of gene
      silencing in nucleic-acid-based therapies. We previously established an HIV-1
      dependent ribozyme-expression vector system, based on Cre-loxP technology with an
      LTR-gag-p17 promoter as a molecular switch for use in acute HIV-1 infection. The
      simultaneous expression of the Cre protein and loxP homologous recombination
      induced a high level of HIV-1-replication inhibition, but ribozyme expression was
      transient. In the current study, we overcame this limitation by inserting EBNA-1
      and oriP genes from the Epstein-Barr virus (EBV) into the vector. When this
      plasmid was introduced into HeLa CD4(+) cells, we observed long-term expression
      of both the EGFP reporter gene and the ribozyme. Moreover, HIV-1 replication was
      inhibited in the long-term in transfected cells. These data suggest that the HIV
      1-dependent ribozyme-expression vector containing EBNA-1/oriP sequences would be
      a useful tool in HIV-1 gene therapy applications.

PMID- 19771215
TI  - RNAi and cancer: Implications and applications.
AB  - RNA interference (RNAi) is an endogenous process that regulates expression of
      genes and corresponding proteins to maintain homeostasis in diverse organisms.
      Non-coding RNAs (ncRNAs) including both long and short ncRNAs are widely
      expressed and levels of some specific microRNAs are different in tumor and non
      tumor tissues. RNAi has been invaluable for unraveling critical pathways involved
      in cancer development, growth and metastasis and has identified critical tumor
      type specific gene targets for chemotherapy. In addition, the development of new
      derivatized small inhibitory RNAs and more efficient methods of their delivery
      will facilitate the future development of these ribonucleotides as cancer
      chemotherapeutic agents.

PMID- 19771217
TI  - Assessment of allele-specific gene silencing by RNA interference with mutant and
      wild-type reporter alleles.
AB  - Allele-specific gene silencing by RNA interference (RNAi) is therapeutically
      useful for specifically suppressing the expression of alleles associated with
      disease. To realize such allele-specific RNAi (ASPRNAi), the design and
      assessment of small interfering RNA (siRNA) duplexes conferring ASP-RNAi is
      vital, but is also difficult. Here, we show ASP-RNAi against the Swedish- and
      London-type amyloid precursor protein (APP) variants related to familial
      Alzheimer's disease using two reporter alleles encoding the Photinus and Renilla
      luciferase genes and carrying mutant and wild-type allelic sequences in their 3'
      untranslated regions. We examined the effects of siRNA duplexes against the
      mutant alleles in allele-specific gene silencing and off-target silencing against
      the wild-type allele under heterozygous conditions, which were generated by
      cotransfecting the reporter alleles and siRNA duplexes into cultured human cells.
      Consistently, the siRNA duplexes determined to confer ASP-RNAi also inhibited the
      expression of the bona fide mutant APP and the production of either amyloid beta
      40- or 42-peptide in Cos-7 cells expressing both the full-length Swedish- and
      wild-type APP alleles. The present data suggest that the system with reporter
      alleles may permit the preclinical assessment of siRNA duplexes conferring ASP
      RNAi, and thus contribute to the design and selection of the most suitable of
      such siRNA duplexes.

PMID- 19771218
TI  - Delivery of RNAi reagents in murine models of obesity and diabetes.
AB  - RNA interference (RNAi) is an exciting new tool to effect acute in vivo knockdown
      of genes for pharmacological target validation. Testing the application of this
      technology to metabolic disease targets, three RNAi delivery methods were
      compared in two frequently utilized preclinical models of obesity and diabetes,
      the diet-induced obese (DIO) and B6.V-Lep<ob>/J (ob/ob) mouse. Intraperitoneal
      (i.p.) and high pressure hydrodynamic intravenous (i.v.) administration of naked
      siRNA, and low pressure i.v. administration of shRNA-expressing adenovirus were
      assessed for both safety and gene knockdown efficacy using constructs targeting
      cJun N-terminal kinase 1 (JNK1). Hydrodynamic delivery of siRNA lowered liver
      JNK1 protein levels 40% in DIO mice, but was accompanied by iatrogenic liver
      damage. The ob/ob model proved even more intolerant of this technique, with
      hydrodynamic delivery resulting in severe liver damage and death of most animals.
      While well-tolerated, i.p. injections of siRNA in DIO mice did not result in any
      knockdown or phenotypic changes in the mice. On the other hand, i.v. injected
      adenovirus expressing shRNA potently reduced expression of JNK1 in vivo by 95%
      without liver toxicity. In conclusion, i.p. and hydrodynamic injections of siRNA
      were ineffective and/or inappropriate for in vivo gene targeting in DIO and ob/ob
      mice, while adenovirus-mediated delivery of shRNA provided a relatively benign
      and effective method for exploring liver target silencing.

PMID- 19771219
TI  - The generation of small RNAs; who needs Dicer?

PMID- 19771220
TI  - RNAi - Is one suffix sufficient?

PMID- 19771221
TI  - A novel expression system for artificial miRNAs containing no endogenous miRNA
      precursor sequences.
AB  - Recently, artificial microRNA (miRNA)-mediated RNA interference (RNAi) systems
      have been developed as useful tools to study gene functions. We report an
      artificial miRNA precursor motif (AMPM) containing several restriction sites in
      the loop and in the extended stem structures, and generated a vector-based
      expression system for AMPM under the control of an RNA polymerase II promoter.
      The AMPM located in the intron or the exon of the selection marker gene mediated
      silencing of the reporter luciferase gene expression in HeLa cells. Northern
      blotting and colony formation assays revealed that the AMPM was efficiently and
      appropriately processed into mature miRNA. The AMPA system also down-regulated
      endogenous p53 and laminA/C proteins in stable transfectants. Moreover, clustered
      AMPMs separated by an appropriate spacer, targeting different sites within a
      single mRNA mediated gene silencing, even if the sequences of the target and the
      AMPM were partially complementary. This indicates the potential therapeutic
      utility of clustered AMPMs for highly-mutable targets, such as human
      immunodeficiency virus type 1.

PMID- 19771222
TI  - A strategy for constructing and verifying short hairpin RNA expression vectors.
AB  - The application of RNA interference (RNAi) to study gene function is now
      commonplace in a variety of biological systems. Producing short hairpin RNA
      (shRNA) by DNA vectors is one popular strategy for RNAi applications. Here, we
      describe a one-step PCR method, termed reverse PCR, for constructing shRNA
      expression vectors. Characteristically, the pair of primers binds to circular
      plasmid in a back-to-back manner. The anchored primers provide the templates of
      shRNA sense strand and antisense strand locating to the two separate ends of PCR
      segment, which will benefit the PCR amplification and subsequent cloning by
      avoiding premature formation of a hairpin configuration. Finally, the
      establishment of a circular vector is achieved by self-ligation of the single PCR
      product. In addition, our results indicated that the hairpin loop including a
      single restriction site is resistant to digestion, while inclusion of twin
      restriction sites in the loop leads to activity, creating an optimal strategy for
      verifying sequences of shRNA template.

PMID- 19771223
TI  - miRNAs and cancer.

PMID- 19771224
TI  - RNAi off-targeting: Light at the end of the tunnel.

PMID- 19771225
TI  - Minimizing off-target effects by using diced siRNAs for RNA interference.
AB  - Microarray studies have shown that individual synthetic small interfering RNAs
      (siRNAs) can have substantial off-target effects. Pools of siRNAs, produced by
      incubation of dsRNAs with recombinant Dicer or RNase III, can also be used to
      silence genes. Here we show that diced siRNA pools are highly complex, containing
      hundreds of different individual siRNAs. This high complexity could either
      compound the problem of off-target effects, since the number of potentially
      problematic siRNAs is high, or it could diminish the problem, since the
      concentration of any individual problematic siRNA is low. We therefore compared
      the off-target effects of diced siRNAs to chemically synthesized siRNAs. In
      agreement with previous reports, we found that two chemically synthesized siRNAs
      targeted against p38alpha MAPK (MAPK14) induced off-target changes in the
      abundance of hundreds of mRNAs. In contrast, three diced siRNA pools against
      p38alpha MAPK had almost no off-target effects. The off-target effects of a
      synthetic siRNA were reduced when the siRNA was diluted 3-fold in a diced pool
      and completely alleviated when it was diluted 30- or 300-fold, suggesting that
      when problematic siRNAs are present within a diced pool, their absolute
      concentration is too low to result in significant off-target effects. These data
      rationalize the observed high specificity of RNA interference in C. elegans and
      D. melanogaster, where gene suppression is mediated by endogenously-generated
      diced siRNA pools, and provide a strategy for improving the specificity of RNA
      interference experiments and screens in mammalian cells.

PMID- 19771226
TI  - 3'-Poly(A) tail enhances siRNA activity against exogenous reporter genes in MCF-7
      cells.
AB  - RNA interference (RNAi) is a powerful tool in the study of gene function. We
      added poly(A) tails to the 3' ends of siRNA antisense strands by in vitro
      transcription, and investigated the silencing effects of poly (A)-tailed siRNAs
      on enhanced green fluorescence protein (EGFP) and red fluorescence protein (RFP)
      genes. The results of this study showed that siRNAs with single-stranded 3'
      poly(A) tails at antisense strands had noticeably stronger silencing effect on
      exogenous reporter genes than their corresponding parental forms. The enhanced
      silencing effect appears to be related to the length of poly(A) but was non siRNA
      sequence-specific. Furthermore, our results demonstrate that weakly-activated PKR
      and reduced stability of mRNAs of exogenous reporter genes in vivo may be the
      possible mechanisms of this non-specific enhanced silencing effect. Our findings
      are likely to be of value in designing siRNAs with enhanced activity.

PMID- 19771227
TI  - Systematic analysis of the role of target site accessibility in the activity of
      DNA enzymes.
AB  - We employed an approach using oligonucleotide scanning arrays and computational
      analysis to conduct a systematic analysis of the interaction between catalytic
      nucleic acids (DNA enzymes or DNAzymes) and long RNA targets. A radio-labelled
      transcript representing mRNA of Xenopus cyclin B5 was hybridised to an array of
      oligonucleotides scanning the first 120 nucleotides of the coding region to
      assess the ability of the immobilised oligonucleotides to form heteroduplexes
      with the target. The hybridisation revealed oligonucleotides showing varying
      levels of signal intensities along the length of the array, reflecting on the
      variable accessibility of the corresponding complementary regions in the target
      RNA. Deoxyribozymes targeting a number of these regions were selected and tested
      for their ability to cleave the target RNA. The mRNA cleavage observed indicates
      that indeed target accessibility was an important component in the activity of
      deoxyribozymes and that it was important that at least one of the two binding
      arms was complementary to an accessible site. Computational analysis suggested
      that intra-molecular folding of deoxyribozymes into stable structures may also
      negatively contribute to their activity. 10-23 type deoxyribozymes generally
      appeared more active than 8-17 type and it was possible to predict deoxyribozymes
      with high cleavage efficiency using scanning array hybridization and
      computational analysis as guides. The data presented here therefore have
      implications on designing effective DNA enzymes.

PMID- 19771228
TI  - 'mi'-nimal interference: Somatic cell reprogramming in cancer and therapy.

PMID- 19771229
TI  - Potent subunit-specific effects on cell growth and drug sensitivity from
      optimised siRNA-mediated silencing of ribonucleotide reductase.
AB  - Ribonucleotide reductase (RR) has an essential role in DNA synthesis and repair
      and is a therapeutic target in a number of different cancers. Previous studies
      have shown that RNAi-mediated knockdown of either the RRM1 or RRM2 subunit
      sensitizes cells to the cytotoxic effects of the nucleoside analogs and more
      recently it has been shown that RRM2 knockdown itself has a growth inhibitory
      effect. Here we compare the effects of siRNA-mediated knockdown of both RRM1 and
      RRM2 subunits of RR in A549 and HCT-116 cells using an optimized transfection
      protocol. Growth of A549 cells was strongly inhibited by efficient siRNA-mediated
      silencing of either RRM1 or RRM2, and knockdown of each subunit led to long-term
      growth inhibition and cell-cycle arrest. Knockdown with sub growth inhibitory
      siRNA concentrations sensitized A549 and HCT-116 cells to gemcitabine when RRM1
      was targeted, whereas RRM2 knockdown led to hydroxyurea sensitization. These
      results suggest that the inhibition of cell growth, rather than drug
      sensitization, is the major effect of RRM1 and RRM2 knockdown. In an A549
      xenograft model, cells transfected with RRM1-specific siRNA failed to form tumors
      in 6 out of 8 CD1 nude mice, whereas those transfected with RRM2-specific siRNA
      grew but at a reduced rate. Taken together, these data demonstrate that siRNA
      mediated knockdown of the RRM1 subunit is more effective than knockdown of RRM2
      in inhibiting the growth of cancer cell lines and suggest that RRM1 is a
      potential target for nucleic acid-based cancer therapies, either alone or in
      combination with gemcitabine.

PMID- 19771230
TI  - Establishment of a positive-readout reporter system for siRNAs.
AB  - The use of small interfering RNA molecules for therapeutic applications requires
      development of improved delivery systems, a process that would be facilitated by
      a non-invasive positive-readout mouse model for studying siRNA pharmacodynamics.
      Positive readout would yield better signal/noise ratios than existing negative
      readout systems. We have engineered a positive-readout luciferase reporter
      system, activated by successful delivery of siRNA targeting the lac repressor. Co
      transfection of a plasmid expressing lac repressor and a plasmid expressing
      firefly luciferase under the control of an RSV promoter, containing two lac
      operator sites, resulted in 5.7-fold lower luciferase activity than luciferase
      encoding plasmid alone. Inhibition was reversed following addition of synthetic
      inducer, IPTG, which elevated luciferase expression to normal levels and
      confirmed functionality of the lac operon. Delivery of 1nM siRNA targeting lac
      repressor to repressor/reporter co-transfected cells was sufficient to fully
      restore luciferase expression to levels observed in the absence of repressor.
      Maximum expression was observed after 48hr, with a rapid decrease thereafter due
      to the short half life of luciferase. The luciferase positive-readout reporter
      system is therefore a dynamic indicator of successful RNAi delivery in vitro and
      could be adapted to generate a transgenic mouse capable of reporting RNAi
      activity non-invasively in vivo.

PMID- 19771231
TI  - Selective RNAi-mediated inhibition of mutated c-kit.
AB  - The proto-oncogene c-kit plays an important role in the development and survival
      of mast cells. Gain-of-function mutations in c-kit are one of the most
      characteristic events in mast cell leukemia (MCL) but as yet there is no
      clinically approved treatment for the disease. Here we describe growth inhibition
      of human MCL cell lines by the use of RNAi against c-kit or its mutant form.
      Retroviral transduction of HMC1.1 and HMC1.2 cell lines with vectors carrying DNA
      to be transcribed to RNAi against the wild type or mutant c-kit messengers
      reduced Kit protein levels considerably, decreased cell proliferation, and
      increased the apoptotic levels five days after retroviral infection. Thus RNAi
      targeted against Kit or its mutant form could be considered as a new
      antiproliferative agent against human mast leukemia cell lines, especially HMC1.2
      cells which are resistant to the Kit tyrosine kinase inhibitor, imatinib
      mesylate.

PMID- 19771232
TI  - Silencing of carbonic anhydrase in an Anopheles gambiae larval cell line, Ag55.
AB  - RNAi has been used extensively to down-regulate proteins in adult mosquitoes;
      however, it is not well adapted for use in larvae. Larval mosquitoes can generate
      a pH as high as 10.5 in the anterior region of their midgut. The mechanisms
      responsible for the generation and maintenance of this pH are not entirely
      understood, but members of the carbonic anhydrase (CA) family of enzymes have
      been implicated. Here we use an An. gambiae larval cell line, Ag55 cells, to
      demonstrate that application of full-length double-stranded RNA specific to one
      CA, AgCA9, is sufficient to silence AgCA9 mRNA and down-regulate the
      corresponding protein. This is a first step towards determining the role(s) of
      these enzymes in pH regulation.

PMID- 19771233
TI  - Non-coding RNAs: Bridging Biology and Therapy.

PMID- 19771235
TI  - The short and the long of UTRs.

PMID- 19771234
TI  - Asymmetrically designed siRNAs and shRNAs enhance the strand specificity and
      efficacy in RNAi.
AB  - RNAi can mediate allele-specific silencing, and offers an attractive approach for
      treatment of human diseases caused by dominant, gain-of-function gene mutations.
      However, allele-specific silencing requires that the RNAi target the mutated
      region of the mRNA, limiting the choices of the target sequences. This often
      results in the use of a suboptimal siRNAs or shRNAs. Unfavorable strand
      asymmetry, which leads to the sense strand rather than the antisense strand to be
      incorporated into RNA-induced silencing complex (RISC), can cause poor RNAi
      efficacy. We systematically tested an approach that places mismatches at or near
      the 5' of the antisense strand to create favorable strand asymmetry. Here we show
      that this approach can enhance the RNAi efficacy of not only siRNAs but also
      shRNAs synthesized from genes, which can be placed in various viral vectors.
      Thus, this design of asymmetric shRNAs could be potentially used in silencing
      dominant, gain-of-function gene mutations for gene therapy.

PMID- 19771236
TI  - RNAi at Oxford.

PMID- 19771237
TI  - Tracking in vitro and in vivo siRNA electrotransfer in tumor cells.
AB  - RNA interference-mediated gene silencing offers the potential of targeted
      inhibition of disease-relevant genes. In vivo delivery of RNAi reagents can be
      obtained by a variety of approaches. Physical delivery methods appear safer and
      lack side effects. Electro-permeabilization is one of the non-viral methods
      successfully used to transfer small interfering RNAs (siRNAs) in vitro and in
      vivo. A promising approach may be, very little is known about the fundamental
      processes mediating siRNA transfer. In this study, we have investigated cellular
      delivery pathways involved in electro-delivery of siRNAs by a direct fluorescence
      imaging method. An Alexa-labeled siRNA was electro-transferred into murine
      melanoma cells stably-expressing the enhanced green fluorescent protein (eGFP)
      target reporter gene. The silencing of eGFP gene expression was quantified by
      time-lapsed fluorescence microscopy. Fluorescently-labeled siRNAs were found
      distributed homogeneously in cytoplasm 48 hours after electro-transfer,
      apparently by diffusion. Furthermore, siRNAs showed homogeneous distribution in
      vivo 48 hrs after intra-tumoral injection followed by electro- permeabilization.
      Histological fluorescence microscopy showed that siRNAs were mostly localized in
      the cytoplasm. Overall, this study shows that electro-permeabilization
      facilitates cytoplasmic distribution of siRNA, both in cultured cells and in
      vivo. This method offers a potential therapeutic tool to facilitate direct siRNA
      penetration into solid tumors.

PMID- 19771238
TI  - Identification and characterisation of the porcine 7SK RNA polymerase III
      promoter for short hairpin RNA expression.
AB  - The RNA polymerase III (pol III) type III promoters U6 and 7SK are routinely used
      to express short hairpin RNA (shRNA) molecules from a DNA construct. In this
      study, we identified, characterised and compared the porcine 7SK promoter in
      porcine (homologous) and non-porcine (heterologous) derived cell lines. The
      porcine 7SK small nuclear RNA (snRNA) was identified by alignment with known
      sequences and further characterisation of the upstream regions determined the
      presence of typical RNA pol III sequence motifs. The porcine 7SK (po7SK) promoter
      was cloned and a one-step PCR strategy used to construct shRNA expression
      cassettes. The 7SK promoter activity was quantified by knockdown of the exogenous
      reporter gene encoding the enhanced green fluorescent protein (EGFP). Results
      indicated the po7SK promoter was functional in both homologous and heterologous
      cells lines. The identification and characterisation of the porcine RNA pol III
      promoter will contribute to the area of RNAi delivery and further develop our
      understanding of RNA promoter structure and function.

PMID- 19771239
TI  - Native microRNA loop sequences can improve short hairpin RNA processing for virus
      gene silencing in animal cells.
AB  - Introduction of small interfering RNAs (siRNAs) into cells results in transitory
      silencing of target genes with complementary sequence. Incorporating siRNAs into
      short-hairpin RNAs (shRNAs) or microRNA-adapted shRNAs (shRNAmir) is a popular
      tool for targeted gene silencing. shRNAmirs mimicking endogenous pre-microRNAs
      (unprocessed hairpin microRNAs) are more difficult to design and result in longer
      RNA molecules. The use of microRNA (miRNA) loop sequences in shRNAs as an
      alternative to an entire pre-microRNA structure on silencing efficiency has not
      been studied extensively. This report shows that loop sequences derived from
      native miRNAs improves the efficiency of silencing due to the processing of the
      shRNAs into mature siRNAs.

PMID- 19771240
TI  - Differential regulation of gene expression in mouse spermatogonial cells after
      blocking c-kit-SCF interaction with RNAi.
AB  - c-Kit, the gene product of the W locus is a receptor tyrosine kinase that
      regulates the survival, growth and differentiation of spermatogonial cells
      (SGCs). Stem cell factor (SCF), the gene product of the steel (Sl) locus is the
      ligand for c-kit. Normal function of SGCs requires cross-talk between c-kit and
      SCF through which the receptor-ligand pair regulates the functions of SGCs. The
      implications of cross-talk between c-kit and SCF in regulating SGC function
      remains unclear due to the molecular complexity of this interaction. In the
      present study, we analyzed the interactions between c-kit and SCF in mouse
      primary SGCs after blocking the c-kit expression by c-kit siRNA and its effect on
      cell fate were determined using cDNA Expression Array and Real-time PCR.
      Immunofluorescence (IF) and western blot studies revealed that c-kit protein was
      detected in SGCs and knocked down to undetectable levels at 24 hr post
      transfection with 10 nM concentration of c-kit siRNA. We further demonstrated
      that expression of various genes involved in cell signaling, cell
      differentiation, apoptosis and cell cycle pathways was altered. SGC functions are
      affected by SCF signaling through c-kit receptor and this signaling appears to be
      important to maintain balance between cell proliferation and apoptosis along with
      the modulation of inflammatory responses of SGCs. To the best of our knowledge,
      this is the first report that identifies the putative molecular pathways in
      murine SGCs in response to specific blocking of c-kit-SCF interactions by siRNA.
      In conclusion, the present study may provide useful insights into siRNA function
      and hopefully aid in understanding the involvement of c-kit in the early events
      of SGC activities and spermatogenesis in mice.

PMID- 19771242
TI  - Lapatinib - overview and current role in metastatic breast cancer.

PMID- 19771241
TI  - Tumor angiogenesis: initiation and targeting - therapeutic targeting of an FGF
      binding protein, an angiogenic switch molecule, and indicator of early stages of
      gastrointestinal adenocarcinomas -.
AB  - Tumor angiogenesis has been related to the initiation as well as progression
      toward more aggressive behavior of human tumors. In particular, the activity of
      angiogenic factors is crucial for tumor progression. We previously characterized
      a secreted fibroblast growth factor-binding protein (FGF-BP) as a chaperone
      molecule, which binds to various FGFs, enhances FGF-mediated biochemical and
      biologic events and importantly is a crucial rate-limiting factor for tumor
      dependent angiogenesis. We generated monoclonal antibodies that target FGF-BP
      protein and used them as a tool to evaluate frequency and pattern of FGF-BP
      expression during the malignant progression of pancreas and colorectal carcinoma
      in archival tissue samples. We found that FGF-BP is dramatically upregulated
      during the initiation of colorectal and pancreatic adenocarcinoma. Crucial
      genetic events underlying the initiation and progression of colorectal and
      pancreatic adenocarcinoma with a particular focus on the modulation of
      angiogenesis and antiangiogenic therapies are discussed. We propose that the
      upregulation of the secreted FGF-BP protein during early phases of pancreas and
      colon cancer could make this protein a possible serum marker indicating the
      presence of high-risk premalignant lesions. Furthermore, the biological activity
      of FGF-BP is neutralized by monoclonal antibodies suggesting the potential for
      antibody-based therapeutic targeting.

PMID- 19771243
TI  - Phase II study of oxaliplatin, 5-fluorouracil, and leucovorin in relapsed or
      metastatic colorectal cancer as second line therapy.
AB  - PURPOSE: The purpose of the study was to assess the efficacy and safety of
      biweekly oxaliplatin in combination with leucovorin (LV)-modulated bolus plus
      infusion of 5-fluorouracil (5-FU) in patients with relapsed or metastatic
      colorectal cancer (CRC) as a second line therapy. MATERIALS AND METHODS: Between
      November 2002 and October 2005, 26 patients with histologically confirmed
      relapsed or metastatic CRC were enrolled. All patients were previously treated
      with irinotecan-based combination chemotherapy. The chemotherapy regimen
      consisted of oxaliplatin 85 mg/m(2) on day 1; LV 200 mg/m(2) on days 1 and 2; and
      5-FU 400 mg/m(2) bolus IV with 600 mg/m(2) with a 22-hour infusion on days 1 and
      2 every 2 weeks. RESULTS: The median age of the 26 patients was 50.5 years
      (range, 31 approximately 72). Their metastatic sites included: the liver (42.3%),
      peritoneum (26.9%), lung (23.1%) and ovary (7.7%). Twenty five patients were
      evaluated for their response. Four patients achieved partial responses and 15
      patients had stable disease. The overall response rate was 16% (95% confidence
      interval; 1.7 approximately 30.3%). The median follow-up duration for the
      surviving patients was 7.4 months (range, 2.08 approximately 21.2). Median
      overall survival (OS) and 1-year OS rates were 16.7 months and 63.9%,
      respectively. The most common hematological toxicities were: NCI grade I/II
      leucopenia (49.3%), grade I/II neutropenia (41%) and grade I/II anemia (65.2%).
      The main non-hematological toxicities were: grade I/II peripheral neuropathy
      (16.1% and 21.5%, respectively) and nausea/vomiting (23.6%/18.5%). There was no
      life-threatening toxicity. CONCLUSION: The oxaliplatin, 5-FU and LV combination
      chemotherapy, scheduled as a biweekly protocol, was effective and well tolerated
      in the treatment of relapsed or metastatic colorectal cancer patients as second
      line chemotherapy.

PMID- 19771244
TI  - Gemcitabine single or combination chemotherapy in post anthracycline and taxane
      salvage treatment of metastatic breast cancer: retrospective analysis of 124
      patients.
AB  - PURPOSE: To evaluate the efficacy of gemcitabine-based chemotherapy, particularly
      in patients with anthracycline- and taxane-pretreated 2(nd)-line or greater
      metastatic breast cancer, and to compare gemcitabine monotherapy (G) with two
      gemcitabine-based doublets, gemcitabine/vinorelbine (GV) and
      gemcitabine/capecitabine (GX). MATERIALS AND METHODS: Of 124 consecutive patients
      who progressed after anthracycline- and taxane-containing chemotherapy, 58
      received G alone, 38 received GV, and 28 received GX; their outcomes were
      analyzed retrospectively. RESULTS: The median number of prior metastatic
      chemotherapy regimens was 2 (range 0 approximately 4). Visceral metastases were
      observed in 65 patients (51.4%). The overall response rate was 19.3% (21 partial
      responses). After a median follow-up period of 21.4 months, the overall survival
      was 7.6 months (95% CI: 5.5 approximately 9.6 months) and the median time to
      progression was 3.1 months (95% CI: 2.0 approximately 4.2 months). Compared with
      monotherapy (G), combination therapy with vinorelbine or capecitabine (GV/GX) was
      associated with a significantly higher response rate (8.2% vs. 28.3%, p=0.008)
      and a significantly longer median time to progression (2.8 vs. 3.5 months;
      p=0.028), but overall survival did not differ between the groups (7.4 vs. 8.2
      months, respectively; p=0.54). Most of the adverse treatment-related events were
      mild to moderate in intensity. The most common adverse event was hematologic
      toxicity. Multivariate analysis showed that poor performance status and a short
      disease-free interval were independent prognostic factors for impaired overall
      survival. CONCLUSIONS: The combination of gemcitabine with vinorelbine or
      capecitabine was an active and well-tolerated treatment option for taxane- and
      anthracycline-pretreated 2(nd)-line or greater metastatic breast cancer patients,
      and gemcitabine-based doublets were more beneficial than gemcitabine monotherapy
      in alleviating symptoms for these patients.

PMID- 19771245
TI  - An evaluation of nutrition support for terminal cancer patients at teaching
      hospitals in Korea.
AB  - PURPOSE: We wanted to analyze the use of nutrition support for terminal cancer
      patients, the effect of discussing withdrawal of nutrition support and do-not
      resuscitate (DNR) consent on the use of intravenous nutrition during the
      patient's last week of life and at the time of death. MATERIALS AND METHODS: The
      study involved 362 patients with terminal cancer from four teaching hospitals,
      and they all died between January 1 2003 and December 31 2005. The basic
      demographic data, the use of intravenous nutrition during the patient's last week
      of life and at death, discussion of terminal nutrition withdrawal and DNR consent
      were evaluated. RESULTS: In the week before death, the patients received
      artificial nutrition such as total parenteral nutrition (31%), intravenous
      albumin infusion (25%), and feeding tube placements (9%). A discussion concerning
      withdrawal of nutrition support was limited to 25 (7%) patients. DNR consent was
      obtained from 294 (81%) patients. None of the patients were directly involved in
      any of these decisions. The discussion about withdrawal of terminal nutrition and
      DNR consent with the patient's surrogates did not have any effect on reducing the
      use of parenteral nutrition. CONCLUSION: The majority of patients dying of
      terminal cancer were still given potentially futile nutritional support. Modern
      clinical guidelines and ethical education about nutritional support at the end of
      life care is urgently needed in Korean medical practice to provide proper
      administration of terminal nutrition for end of life care.

PMID- 19771246
TI  - Prognostic significance of immunohistochemical expression of p53 gene product in
      operable breast cancer.
AB  - PURPOSE: The aim of this study was to investigate the prognostic significance of
      the expression of p53 gene product in operable invasive breast cancer by
      performing immunohistochemical analysis. MATERIALS AND METHODS: Between January
      1993 and December 2001, 440 operable invasive breast cancer patients underwent
      immunohistochemical staining for p53, and we retrospectively analyzed these
      results together with the clinical outcomes. RESULTS: The overexpression of p53
      was detected in 51.6% of the cases. The overexpression of p53 was inversely
      correlated with lymph node metastasis (p=0.005). The tumor size, tumor histology,
      histologic grade, hormonal receptor status and tumor stage were not related to
      the overexpression of p53. Multivariate Cox regression analysis indicate that
      lymph node metastasis, tumor size and the p53 expression were the significant
      prognostic factors for overall survival; lymph node metastasis, the estrogen
      receptor status and the p53 expression were the significant prognostic factors
      for relapse free survival. On the subgroup analysis, the p53 non-expressors
      showed better 7-year overall survival (92.7% vs. 76.7%, respectively, p=0.011)
      and relapse free survival (74.9% vs. 57.8%, respectively, p=0.032) than did the
      p53 overexpressors for the patients with lymph node metastasis. However, for the
      patients without lymph node metastasis, the survival rates were not different for
      both the p53 non-expressors and the p53 overexpressors. CONCLUSION:
      Immunohistochemical staining of the p53 gene product was an independent
      prognostic factor for predicting survival of the lymph node positive invasive
      breast cancer patients.

PMID- 19771247
TI  - p53 prevents immature escaping from cell cycle G2 checkpoint arrest through
      inhibiting cdk2-dependent NF-Y phosphorylation.
AB  - PURPOSE: Recent studies have suggested that p53 regulates the G2 checkpoint in
      the cell cycle and this function is required for the maintenance of genomic
      integrity. In this study, we addressed a role of p53 in escaping from cell cycle
      G2 arrest following DNA damage. MATERIALS AND METHODS: Cell cycle checkpoint
      arrest in the human colon cancer cell line HCT116 and its derivatives carry p53
      or p21 deletions, were examined by FACS analysis, immunoprecipitation, Western
      blot and IP-kinase assay. RESULTS: While the cells with functional p53 were
      arrested at both the G1 and G2 checkpoints, the p53-deficient cells failed to
      arrest at G1, but they were arrested at G2. However, the p53-deficient cells
      failed to sustain G2 checkpoint arrest and they entered mitosis earlier than did
      the p53-positive cells and so this resulted in extensive cell death. Cdc2 kinase
      becomes reactivated in p53-deficient cells in association with entry into
      mitosis, but not in the p53-positive cells. Upon DNA damage, the p21-deficient
      cells, like the p53-negative cells, not only failed to repress cdk2-dependent NF
      Y phosphorylation, but they also failed to repress the expression of such cell
      cycle G2-regulatory genes as cdc2, cyclin B, RNR-R2 and cdc25C, which have all
      been previously reported as targets of NF-Y transcription factor. CONCLUSIONS:
      p53 is essential to prevent immature escaping from cell cycle G2 checkpoint
      arrest through p21-mediated cdk2 inactivation, and this leads to inhibition of
      cdk2-dependent NF-Y phosphorylation and NF-Y dependent transcription of the cell
      cycle G2-regulatory genes, including cdc2 and cyclin B.

PMID- 19771248
TI  - The effect of pentoxifylline on radiobiological parameters in the rat radiation
      myelopathy.
AB  - PURPOSE: There is great recent interest in the potential value of using
      pentoxifylline (3,7-dimethyl-1(5-oxyhexyl)-xanthine, PTX) as an inhibitor of
      radiation-induced late normal tissue damage. The effects of PTX on the
      radiobiological parameters (alpha/beta ratio, repair half time T(1/2)) of
      radiation myelopathy were studied in a rat model. MATERIALS AND METHODS:
      Anesthetized Sprague-Dawley rats received irradiation to 2 cm of their cervical
      spines with using a 6MV LINAC (dose rate: 3 Gy/min). Radiation was administered
      in single, two, four and eight fractions with a fraction interval of 24 h with or
      without PTX. PTX was added to the rats' distilled drinking water at a
      concentration of 2 g/L; the water was consumed ad libitum. After tabulation of
      the ED(50) (the estimated dose needed to produce 50% paralysis in a group of
      irradiated animals), alpha/beta could be estimated from the ratio of the slope to
      the intercept of the reciprocal-dose plot. Subsequently, the repair half time
      T(1/2) was obtained from the data of the experimental group that received a pair
      of 7 Gy fractions on each day, separated by intervals of 4 and 8 h. RESULTS: The
      alpha values calculated for RT alone and RT+ PTX were almost the same. We noticed
      that the beta value for the RT+PTX was lower than that for RT alone. So, the
      alpha/beta ratio for the RT+PTX was higher. The T(1/2) obtained from
      monoexponential model was 3.27 and 2.58 h for RT alone and RT+PTX, respectively.
      CONCLUSION: PTX increased the alpha/beta ratio and it decreased the T(1/2) of
      radiation myelopathy, suggesting that a decreasing fractionation sensitivity
      occurred. This implies that PTX, which distinctly acts upon the bending region of
      the high dose, may be expected to protect the spinal cord with a larger fraction
      size.

PMID- 19771250
TI  - Hypersensitivity reactions to oxaliplatin.
AB  - Oxaliplatin is a third-generation platinum compound that is used as a single
      agent and in combination with fluorouracil (5-FU) to treat colorectal and gastric
      carcinoma. The patients treated with oxaliplatin may develop hypersensitivity and
      idiosyncratic reactions, although these complications are known to be rare. We
      report here on two patients who suffered with metastatic colorectal cancer and
      who underwent palliative combination chemotherapy with oxaliplatin; they then
      developed hypersensitivity reactions to oxaliplatin. The first case had an
      anaphylatic reaction immediately after the beginning of the 7(th) to 8(th) cycle
      infusion of oxaliplatin. The second case developed repeated febrile episodes from
      the 4(th) to 8(th) cycles of oxaliplatin infusion. With the increasing use of
      oxaliplatin in clinical practice, we are now encountering an increasing incidence
      of suspected hypersensitivity reactions. Physicians should keep their eyes wide
      open and carefully observe for the clinical manifestations of these
      hypersensitivity reactions.

PMID- 19771249
TI  - Mouse orthotopic lung cancer model induced by PC14PE6.
AB  - PURPOSE: This study was undertaken to investigate in detail the xenograft mouse
      orthotopic lung cancer model induced by PC14PE6 adenocarcinoma cells. MATERIALS
      AND METHODS: Three cell doses (0.5x10(6); 1x10(6); 2x10(6)) of PC14PE6 cells were
      injected into the lungs of male BALB/c nude mice by the intrathoracic injection
      method. The lung and other organs, including brain, liver, spleen, kidney,
      muscle, adrenal gland, and lymph node on knee, were removed and stained with H/E
      to detect the presence of tumor cells. RESULTS: The reliable tumorigenicity time
      in the PC14PE6 adenocarcinoma cell-inoculated BALB/c nude mouse was 10 days after
      intrathoracic injection. The average life span of the three groups after
      inoculation was 14 days in the 2x10(6) cells inoculum group; 25 days in the
      1x10(6) cells inoculum group; and 32 days in the 0.5x10(6) cells inoculum group.
      The PC14PE6 adenocarcinoma cells induced orthotopic lung cancer limited within
      the thorax. CONCLUSIONS: This orthotopic lung cancer model is an efficient cancer
      model with easy inoculation methods, rapid and high tumorigenicity, and simple
      monitoring methods for metastasis.

PMID- 19771251
TI  - Tissue array methods for high-throughput clinicopathologic research.
AB  - Recent research in molecular biology has identified a significant number of novel
      markers, which may have diagnostic, prognostic and therapeutic significance. High
      throughput tissue array method facilitates the validation of novel markers by
      enabling the simultaneous analysis of hundreds or thousands of tissue specimens.
      Tissue array slides can be analyzed using techniques such as immunohistochemistry
      and in situ hybridization. In this review, we give a brief overview of tissue
      array method and its application to high throughput clinicopathologic research.

PMID- 19771252
TI  - Long term trends and the future gastric cancer mortality in Korea: 1983~2013.
AB  - PURPOSE: In spite of gastric cancer's decreasing incidence and mortality rates,
      it is still the most common cancer in Korea. In the present study, we examined
      the temporal trends of gastric cancer mortality during the past 20 years in Korea
      by using an age-period-cohort model, and we predicted the mortality rates for the
      next 10 years. MATERIALS AND METHODS: Data on the annual number of deaths due to
      gastric cancer and data on population statistics from 1984 to 2003 were obtained
      from the Korean National Statistical Office. A log-linear Poisson age-period
      cohort model was used to estimate age, period and birth cohort effects. To
      project two periods (10 years) into the future, the new cohort values were
      estimated by performing linear regression that was applied to a chosen number of
      the most recent cohort values. RESULTS: The trends of gastric cancer mortality
      were predominantly explained by the cohort effect; the risk of gastric cancer
      death decreased since the 1919 birth cohort for both genders. The predicted,
      expected age-adjusted mortality rates per 100,000 for males and females are 45.74
      [corrected] and 23.70 [corrected] respectively, during 2004~2008, and 27.77
      [corrected] and 14.92 [corrected] respectively, during 2009~2013. During
      2004~2008 and 2009~2013, the predicted numbers of deaths due to gastric cancer in
      males are 36,940 [corrected] and 27,967 [corrected], respectively, whereas those
      in females are 19,658 [corrected] and 14,843 [corrected], respectively.
      CONCLUSIONS: Not only the mortality, but also the incidence of gastric cancer in
      Korea is expected to further decrease in both men and women if the trends of the
      past 20 years continue.

PMID- 19771253
TI  - Prognostic factors for advanced gastric cancer: stage-stratified analysis of
      patients who underwent curative resection.
AB  - PURPOSE: Advanced gastric cancer patients have a poorer prognosis as compared to
      the patients with early gastric cancer. This study was conducted to define the
      prognostic factors for advanced gastric cancer. MATERIALS AND METHODS: 606
      patients with advanced gastric cancer who underwent curative gastric resection at
      our hospital were retrospectively examined. The patients were divided into two
      groups: group 1 was comprised of patients with a survival time <5 years, and
      group 2 patients had a survival time >or=5 years. We compared clinicopathological
      characteristics of the two groups by performing univariate and multivariate
      analysis. We also investigated the prognostic factors according to the stage.
      RESULTS: On univariate analysis, 7 factors (age, tumor size, Borrmann type,
      resection type, distal resection margin, depth of invasion and lymph node status)
      were found to be different, and multivariate analysis revealed that patient age,
      depth of invasion and lymph node metastasis were the only significantly
      differences between the two groups. On the other hand, age and the Borrmann type
      for stage I b patients, age and the number of retrieved lymph nodes for stage II
      patients, tumor size for stage III patients, and the type of resection for stage
      IV patients were found to be the independent prognostic factors. CONCLUSION: The
      age of patients had prognostic value in the early stages of advanced gastric
      cancers such as stage I b or II. The number greater than 20 retrieved lymph nodes
      affected the survival, particularly for the patients with stage II disease, and
      the tumor size was a significant prognostic factor for patients with stage III
      disease. Therefore, physicians are advised to pay special attention to lymph node
      dissection for those patients with stage II or III disease.

PMID- 19771254
TI  - Increased ERCC expression correlates with improved outcome of patients treated
      with cisplatin as an adjuvant therapy for curatively resected gastric cancer.
AB  - PURPOSE: It has been reported that the overexpression of the excision repair
      cross-complementing 1 (ERCC1) gene, which is essential for the repair of
      cisplatin (CDDP)-DNA adducts, negatively influences the effectiveness of CDDP
      based therapy for primary gastric cancer. We investigated whether the ERCC1
      expression was associated with survival for gastric cancer patients in an
      adjuvant setting. MATERIALS AND METHODS: We retrospectively analyzed 44 patients
      who were diagnosed with stage II or higher disease after undergoing curative
      resection and they had also received cisplatin-based chemotherapy. The ERCC1
      expression was examined by performing immunohistochemical (IHC) staining, and
      this was divided into two groups according to the percentage of IHC staining of
      the tumor cell nuclei (negative: 10% or less, positive: more than 10%). RESULTS:
      Among the 44 patients (ERCC1-negative/ERCC1-positive group=16/28), 32 patients
      were male and their median age was 52 years. There was no difference for the
      baseline characteristics of the two groups. The median follow-up duration was 41
      months. The median disease-free survival (DFS) and the overall survival (OS) for
      the ERCC1-positive group were significant higher than those of the ERCC1-negative
      group (DFS: 40.4 vs. 14.6 months, p=0.02, OS: undefined vs. 20.4 months,
      p=0.008). CONCLUSION: The overall survival in gastric cancer patients who
      received cisplatin-based adjuvant chemotherapy after a curative resection is
      higher in those patients showing the overexpression of the ERCC1 gene. However,
      prospective studies using the ERCC1 gene expression as a prognostic marker for
      the DNA repair activity are needed.

PMID- 19771255
TI  - Characteristics of synchronous cancers in gastric cancer patients.
AB  - PURPOSE: The primary objective of the current study was to investigate the
      characteristics of synchronous cancers in gastric cancer patients. MATERIALS AND
      METHODS: We analyzed the 2,237 patients who were diagnosed between December 2000
      and December 2003 with gastric cancer and synchronous cancers of organs other
      than the stomach. RESULTS: 73 (3.3%) of a total of 2,237 gastric cancer patients
      had synchronous primary cancers. Among these 73 patients, 71 had one synchronous
      cancer, and two patients had double synchronous cancers. Colorectal cancer (26
      patients, 34.7%) was the most frequently encountered synchronous cancer, followed
      by cancer of the lung (16 patients, 21.3%), esophagus (13 patients, 17.2%), and
      liver (8 patients, 10.7%). Synchronous cancers were detected with increased
      frequency in the elderly, in the patients with multiple gastric cancers, in the
      patients with differentiated gastric cancer, and in the patients with early
      gastric cancer, as determined on univariate analysis, but the differentiation of
      gastric cancers was the only risk factor for synchronous cancers on the
      multivariate analysis. CONCLUSIONS: The differentiation of gastric cancer cells
      may be a risk factor for synchronous cancers in gastric cancer patients. Careful
      surveillance by the physician for synchronous cancer is warranted for the
      patients suffering from gastric cancer.

PMID- 19771256
TI  - Optimal timing for the administration of capecitabine with preoperative
      chemoradiation for locally advanced rectal cancer.
AB  - PURPOSE: Capecitabine is an oral fluoropyrimidine carbamate and it is known as an
      effective radiosensitizer. Capecitabine and its metabolite reach their peak
      concentration in the plasma at 1 approximately 2 hours after a single oral
      administration of capecitabine and the levels fall rapidly thereafter. To verify
      the radiosensitizing effect of capecitabine that is based on such pharmacokinetic
      characteristics, we performed a retrospective analysis on the optimal timing of
      capecitabine administration with performing preoperative chemoradiation for
      locally advanced rectal cancer. MATERIALS AND METHODS: Among 171 patients who
      were treated with preoperative radiotherapy and concurrent capecitabine
      administration for rectal cancer, 56 patients were administered capecitabine at
      1~2 hours before radiotherapy (group A), and at other time in the other 115
      patients (group B). Total mesorectal excision was done at 4 to 6 weeks after the
      completion of chemoradiation. The radiosensitizing effect of capecitabine was
      evaluated on the basis of the pathological response. RESULTS: Complete
      pathological regression of the primary tumor was observed in 12 patients (21.4%)
      for group A and in 11 patients (9.6%) for group B (p=0.031). Residual disease
      less than 0.5 cm (a good response) was observed in 19 patients (33.9%) for group
      A and in 23 patients (20.0%) for group B (p=0.038). On multivariate analysis, the
      capecitabine ingestion time showed marginal significance. CONCLUSION: When
      performing preoperative chemoradiation for locally advanced rectal cancer, the
      radiosensitizing effect of capecitabine was enhanced when it was administered 1
      hour before radiotherapy.

PMID- 19771257
TI  - Serum HER2 as a response indicator to various chemotherapeutic agents in tissue
      HER2 positive metastatic breast cancer.
AB  - PURPOSE: The aim of study was to evaluate the usefulness of serum HER2 as a
      therapeutic response indicator in patients with HER2 positive metastatic breast
      cancer (MBC). MATERIALS AND METHODS: The levels of serum HER2 and CA15.3 were
      assayed in 148 serial serum samples from 50 HER2 positive MBC patients at both
      the baseline and follow-ups. The changes in the levels of serum HER2 and CA15.3
      in relation to the tumor responses to the various chemotherapy regimens were
      monitored. RESULTS: The levels of serum HER2 and CA15.3 were elevated in 82% and
      62% of tissue HER2 positive patients, respectively, prior to therapies, with the
      changes in both tumor markers showing statistical significance in relation to the
      tumor responses (p<0.01) in patients with elevated baseline serum markers.
      CONCLUSION: The level of serum HER2 could be a valuable response indicator, not
      only for trastuzumab containing therapy, but also for other common MBC
      chemotherapeutic agents. Also, as it is more frequently elevated, the serum level
      of HER2 may also be a more useful tumor marker than CA15.3 in HER2 positive MBC.

PMID- 19771258
TI  - The effect of simulation on recurrence after breast-conserving surgery and
      radiotherapy: preliminary results.
AB  - PURPOSE: To evaluate the effect of the simulation method on recurrence among the
      patients who received radiotherapy after breast-conserving surgery (BCS) for
      early breast carcinoma. MATERIALS AND METHODS: Between 1995 and 2000, 70 patients
      with stage I-II breast carcinoma underwent breast-conserving surgery and adjuvant
      radiotherapy. Twenty nine patients (41.4%) were simulated with the 2D contour
      based method (September 1995 to August 1997) and 41 patients (58.6%) were
      simulated with the 3D CT-based method (September 1997 to February 2000). To
      analyze the effect of the simulation method, the patient and treatment
      characteristics were compared. RESULTS: The characteristics were similar for the
      patients between the 2D contour-based simulation group and the 3D CT-based
      simulation group. During a median follow-up period of 75 months, 4 (13.8%) of 29
      patients who were treated with 2D simulation and 1 (2.4%) of 41 patients who were
      treated with 3D simulation group developed treatment failure. The five-year
      survival rates were 89.2% and 95.1% between the 2D and 3D simulation groups
      (p=0.196). The five-year disease free survival (DFS) rates were 86.2% and 97.5%
      between the 2D and 3D simulation groups (p=0.0636). On univariate analysis, age >
      40 (p= 0.0226) and the number of dissected axillary lymph node >or= 10 (p=0.0435)
      were independent predictors of improved 5-year DFS. CONCLUSIONS: Although our
      data showed marginal significance for the DFS between the two groups, it is
      insufficient, due to the small number of patients in our study, to prove whether
      3D CT-based simulation might improve the DFS and reduce the risk of recurrence
      when compared with 2D contour-based simulation. Further study is needed with a
      larger group of patients.

PMID- 19771259
TI  - Resveratrol at high doses acts as an apoptotic inducer in endothelial cells.
AB  - PURPOSES: Resveratrol is a phenolic compound found in grapes and other food
      products. In order to assess the availability of resveratrol as an angio
      inhibiting drug, we examined whether resveratrol plays an important role in
      bovine aortic endothelial cells (BAECs) for cell apoptosis and cell migration.
      METHODS AND MATERIALS: Endothelial cell apoptosis was observed as detected by the
      Hoechst staining and the caspase-3 activity. Additionally, Western blotting was
      performed for monitoring the activities of various cell signaling molecules.
      RESULTS: Resveratrol was shown to act as a pro-apoptotic agent. The pro-apoptotic
      effect of resveratrol was as great as that of etoposide, a well-known anti-cancer
      drug. In addition, resveratrol had an inhibitory effect on endothelial cell
      migration. The demonstrated efficacy of resveratrol suggests that resveratrol may
      be utilized as an anti-angiogenic drug. To determine the underlying mechanisms,
      we further investigated which signaling molecules are activated by resveratrol.
      Extracellular signal-regulated kinase (ERK) was activated by the treatment with
      resveratrol in BAECs, whereas endothelial nitric oxide synthetase (eNOS), Akt,
      and Jun N-terminal kinase (JNK) were inhibited. The pretreatment with PD
      compound, an ERK inhibitor, had no effect on the pro-apoptosis induced by
      resveratrol. CONCLUSION: Resveratrol plays an important role in endothelial cell
      apoptosis, indicating that resveratrol can be utilized as a potent anti
      angiogenic drug.

PMID- 19771260
TI  - Arsenic trioxide induces apoptosis in human colorectal adenocarcinoma HT-29 cells
      through ROS.
AB  - PURPOSE: Treatment with arsenic trioxide (As(2)O(3)) results in a wide range of
      cellular effects that includes induction of apoptosis, inhibition of cell growth,
      promotion or inhibition of cellular differentiation, and inhibition of
      angiogenesis through a variety of mechanisms. The mechanisms of As(2)O(3)-induced
      cell death have been mainly studied in hematological cancers, and those
      mechanisms in solid cancers have yet to be clearly defined. In this study, the
      mechanisms by which As(2)O(3) induces apoptosis in human colorectal
      adenocarcinoma HT-29 cells were investigated. MATERIALS AND METHODS: To examine
      the levels of apoptosis, HT-29 cells were treated with As(2)O(3) and then we
      measured the percentage of Annexin V binding cells, the amount of ROS production
      and the mitochondrial membrane potential. Western blot analysis was performed to
      identify the activated caspases after As(2)O(3) exposure, and we compared the
      possible target molecules of apoptosis. As(2)O(3) treatment induced the loss of
      the mitochondrial membrane potential and an increase of ROS, as well as
      activation of caspase-3, -7, -9 and -10. RESULTS: As(2)O(3) induced apoptosis via
      the production of reactive oxygen species and the loss of the mitochondrial
      membrane potential. As(2)O(3) induced the activation of caspase-3, -7, -9 and 
      10. Furthermore, As(2)O(3) treatment downregulates the Mcl-1 and Bcl-2
      expressions, and the release of cytochrome c and an apoptosis-inducing factor
      (AIF). Pretreating the HT-29 cells with N-acetyl-L-cysteine, which is a thiol
      containing antioxidant, inhibited the As(2)O(3)-induced apoptosis and caspase
      activation. CONCLUSION: Taken together, these results suggest that the generation
      of reactive oxygen species (ROS) by As(2)O(3) might play an important role in the
      regulation of As(2)O(3)-induced apoptosis. This cytotoxicity is mediated through
      a mitochondria-dependent apoptotic signal pathway in HT-29 cells.

PMID- 19771261
TI  - Number of radiation oncologists in Korea, adequate or surplus?
AB  - PURPOSE: The purpose of this research is to discern and address the issues
      related to the radiation oncology manpower supply and its distribution. MATERIALS
      AND METHODS: The statistical data of the Annual Report of the Korea Central
      Cancer Registry (KCCR) from 1997 to 2002 and the Annual Report of the Korean
      Society of Radiation Oncology (KOSTRO) from 1997 to 2004 were used to predict the
      status of the human resources in 2015. The estimated demand and supply were
      calculated with the Microsoft Excel program (Microsoft, Redmond, WA). RESULTS:
      The demand for radiation oncologists is estimated to be 161 in 2015 and about 4.9
      radiation oncologists will be in demand annually. In contrast, an average of 15
      new radiation oncologists will be supplied annually so that the accumulated
      surplus of radiation oncologists until 2015 is estimated to be 74.1. The main
      reason for the surplus comes from the discrepancy between the increased number of
      radiation therapy patients and the need for radiation oncologists. When there is
      an increase of 1,000 radiation therapy patients, the demand for radiation
      oncologists increases only by 2.4. This phenomenon is especially evident in the
      top 10 hospitals where the average number of radiation therapy patients per
      radiation oncologist is 341, which is 58% higher than the average number (215) of
      other 46 hospitals. CONCLUSION: To prevent a surplus and to maintain the quality
      of management, the number of radiation therapy patients per radiation oncologist
      should be limited. Furthermore, coordinate control of the number of residency
      positions should be seriously considered.

PMID- 19771262
TI  - The efficacy and safety of Padexol (paclitaxel) and cisplatin for treating
      advanced non-small cell lung cancer.
AB  - PURPOSE: The authors conducted a multicenter study to evaluate the efficacy and
      safety of combination chemotherapy with Padexol and cisplatin for treating
      patients with advanced non-small cell lung cancer (NSCLC). MATERIALS AND METHODS:
      From November 2003 to April 2005, 42 chemo-naive patients with advanced NSCLC
      were enrolled into this study from 4 hospitals. The treatment consisted of
      Padexol 175 mg/m(2) as a 3-hr infusion, and this was followed by cisplatin 75
      mg/m(2) administered as an intravenous infusion with standard premedication. The
      treatment was repeated every 3 weeks. RESULTS: Among the 42 patients (pts), 33
      pts were evaluable for response. On the per protocol analysis, 1 patient (pt)
      (3.0%) achieved complete response (CR), 17 pts (51.5%) achieved partial response
      (PR), 6 pts (18.2%) achieved stable disease (SD), and 9 pts (27.3%) progressed;
      therefore, the overall response rate was 54.6% (95% CI: 37.6 approximately
      71.5%). On the intention-to-treat analysis, 1 pt (2.4%) achieved CR, 18 pts
      (42.9%) achieved PR, 11 pts (26.2%) achieved SD, and 9 pts (21.4%) progressed;
      therefore, the overall response rate was 45.2% (95% CI: 30.2 approximately
      60.3%). The response, as evaluated by the investigators, was independently
      reviewed by 2 external radiologists and it was as follows; 13 PR (43.3%), 14 SD
      (46.7%) and 3 progressive disease (10%). The median duration of response was 5.9
      months. The median follow-up duration was 10.3 months (range: 1.3 to 22.1
      months). The median time to progression was 5.8 months (95% CI: 4.7 to 7.4
      months). The median survival time on the intention-to-treat analysis was 10.5
      months (95% CI: 8.1 to 18.8 months). The most common grade 3 or 4 hematologic
      toxicities were neutropenia (26/180 cycles, 14.4%), anemia (7/180 cycles, 3.9%)
      and febrile neutropenia (2/180 cycles, 1.1%). The most frequent grade 3 or 4 non
      hematologic toxicities were nausea (14/42 patients, 14.3%), anorexia (3/42
      patients, 7.1%) and myalgia (3/42 patients, 7.1%). CONCLUSION: The authors
      observed that Padexol was as good as the other paclitaxel (Taxol or Genexol)
      formulations when combined with cisplatin for treating patients with advanced
      NSCLC.

PMID- 19771263
TI  - A phase II study of irinotecan, 5-fluorouracil and leucovorin for treatment in
      patients with previously untreated advanced colorectal cancer.
AB  - PURPOSE: We prospectively conducted a non-randomized phase II trial to evaluate
      the efficacy and safety of combination irinotecan, leucovorin (LV) and 5
      fluorouracil (FU) as a first-line regimen for treating patients with previously
      untreated advanced colorectal cancer (CRC). MATERIALS AND METHODS: Twenty-six
      previously untreated patients with advanced, recurrent or metastatic CRC were
      enrolled in this study. The patients received either irinotecan 180 mg/m(2) on
      day 1 with LV bolus of 200 mg/m(2) and FU bolus of 400 mg/m(2), and this was
      followed by FU continuous infusion of 600 mg/m(2) on day 1 and day 2 (the FOLFIRI
      regimen), or they were treated with LV bolus of 400 mg/m(2) and FU bolus of 400
      mg/m(2) followed by FU continuous infusion of 2,400 mg/m(2) for 46 hours (the
      simplified FOLFIRI regimen), and these treatments were repeated every 2 weeks
      until disease progression. RESULTS: The objective response rate was 23.1% (6/26)
      respectively, for both treatments. The median time to progression was 5.3 months
      (range: 0.4 approximately 19.9), and the overall survival was 11.2 months (range:
      0.5 approximately 52.3). The prognostic factor for longer survival was the
      Eastern Cooperative Oncology Group (ECOG) performance status (PS). The non
      hematological toxicities were similar for both treatment groups, with more
      frequent grade >or=3 neutropenia being noted for the simplified FOLFIRI regimen.
      CONCLUSION: The biweekly irinotecan based regimen was demonstrated to have a
      moderate antitumor activity with acceptable toxicity profiles, and the ECOG PS
      was the independent prognostic factor.

PMID- 19771264
TI  - Efficacy of combined gemcitabine/cisplatin chemotherapy for locally advanced or
      metastatic urothelial cancer.
AB  - PURPOSE: We wanted to determine and report on the outcome of combined
      gemcitabine/cisplatin chemotherapy for patients suffering with locally advanced
      or metastatic urothelial cancer. MATERIALS AND METHODS: Between July 1999 and
      December 2004, 43 selected patients were enrolled in this study. Group 1 (the
      adjuvant chemotherapy group) had undergone radical surgery with removal of
      evident tumor from the following primary sites: bladder (n=8), renal pelvis (n=7)
      and ureter (n=3). Group 2 (the salvage chemotherapy group) had undergone
      palliative surgery with a remnant tumor at the following primary sites; bladder
      (n=23) and renal pelvis (n=2). All the patients were given gemcitabine/ciplatin
      and they evaluated for the therapeutic effect and toxicity. The patients were
      initially treated with gemcitabine 1000 mg/m(2) intravenously for 30 minutes on
      days 1, 8 and 15 of a 28-day cycle, and cisplatin 70 mg/m(2) was administered
      intravenously on day 1 using prehydration measures. RESULTS: Group 1: The median
      follow-up period was 16.5 months. The mean age was 63 years (males: 15 cases,
      females: 3 cases), and eleven patients (61%) remained alive. The estimated median
      relapse-free survival period and 2-year survival rate were 24 months and 63%,
      respectively. Group 2: the median follow-up period was 20 months, the mean
      patient age was 63.8 years (males: 22 cases, females: 3 cases), and nine patients
      (36%) remained alive. The overall response and 2-year survival rates were 36% and
      43%, respectively. Toxicities: Grade 3 toxicities developed in 14 cycles during
      the total 232 cycles. Grade 4 toxicity did not occur. CONCLUSIONS: The results of
      this study confirm that adjuvant and salvage chemotherapy with using gemcitabine
      and cisplatin is tolerable and safe.

PMID- 19771265
TI  - Evaluation of parotid gland function following intensity modulated radiation
      therapy for head and neck cancer.
AB  - PURPOSE: This study was undertaken to determine the parotid gland tolerance dose
      levels following intensity modulated radiation therapy (IMRT) for treating
      patients who suffered with head and neck cancer. MATERIALS AND METHODS: From
      February 2003 through June 2004, 34 head and neck patients with 6 months of
      follow-up were evaluated for xerostomia after being treated by IMRT. Their median
      age was 59 years (range: 29~78). Xerostomia was assessed using a 4-question
      xerostomia questionnaire score (XQS) and a test for the salivary flow rates
      (unstimulated and stimulated: USFR and SSFR, respectively). The patients were
      also given a validated LENT SOMA scale (LSS) questionnaire. Evaluations were
      performed before IMRT and at 1, 3 and 6 months after IMRT. RESULTS: All 34
      patients showed significant changes in the XQS, LSS and Salivary Flow rates (USFR
      and SSFR) after IMRT. No significant changes in the XQS or LSS were noted in 12
      patients who received a total parotid mean dose of <or=3,100 cGy at 1, 3 and 6
      months post-IMRT relative to the baseline values. However, for the 22 patients
      who received >3,100 cGy, significant increases in the XQS and LSS were observed.
      The USFR and SSFR from the parotid glands in 7 patients who received <or=2,750
      cGy were significantly preserved at up to 6 months after IMRT. However, the USFR
      and SSFR in 27 patients who were treated with >2,750 cGy were significantly lower
      than the baseline values at all times after IMRT. CONCLUSION: We suggest that the
      total parotid mean dose should be limited to <or=2,750 cGy to preserve the USFR
      and SSFR and so improve the subsequent quality of life.

PMID- 19771266
TI  - Overexpression of alpha1-protease inhibitor and galectin-1 in radiation-induced
      early phase of pulmonary fibrosis.
AB  - PURPOSE: Radiation-induced pulmonary fibrosis (RIF) is a significant complication
      of radiotherapy for lung cancer. Despite the large number of studies, the
      molecular mechanisms of RIF are poorly understood. Therefore, the complex protein
      expression pattern in RIF was characterized by identifying the proteins with an
      altered expression level after thorax irradiation using two-dimensional
      electrophoresis (2-DE) and mass spectrometry. MATERIALS AND METHODS: A mouse
      model of RIF was used to examine the alteration of the lung proteome because of
      availability of murine data related to human cases and the abundance of murine
      fibrotic lung samples. A mouse model of RIF was induced in radiosensitive C57BL/6
      mice. Twenty-one weeks after 25 Gy irradiation, hematoxylin-eosin staining and
      hydroxyproline assay confirmed the early-phase pulmonary fibrosis. RESULTS: Lung
      samples from the irradiated and age-matched control mice were used to generate 16
      high quality 2-DE gels containing approximately 1,000 spots. Of the 31
      significantly up- or down-regulated protein spots, 17 were identified by MALDI
      TOF/MS. CONCLUSIONS: Two important upregulated proteins were found, the alpha1
      protease inhibitor and galectin-1, which might be used as potential markers for
      the early phase of RIF.

PMID- 19771267
TI  - Protein expression profile using two-dimensional gel analysis in squamous
      cervical cancer patients.
AB  - PURPOSE: Screening in cervical cancer is now progressing to discover candidate
      genes and proteins that may serve as biological markers and that play a role in
      tumor progression. We examined the protein expression patterns of the squamous
      cell carcinoma (SCC) tissues from Korean women with using two- dimensional
      polyacrylamide gel electrophoresis (2-DE) and matrix assisted laser
      desorption/ionization-time of flight (MALDI- TOF) mass spectrometer. MATERIALS
      AND METHODS: Normal cervix and SCC tissues were solubilized and 2-DE was
      performed using pH 3 approximately 10 linear IPG strips of 17 cm length. The
      protein expression was evaluated using PDQuest 2-D software. The differentially
      expressed protein spots were identified with a MALDI-TOF mass spectrometer, and
      the peptide mass spectra identifications were performed using the Mascot program
      and by searching the Swiss-prot or NCBInr databases. RESULTS: A total of 35
      proteins were detected in SCC. 17 proteins were up-regulated and 18 proteins were
      down-regulated. Among the proteins that were identified, 12 proteins (pigment
      epithelium derived factor, annexin A2 and A5, keratin 19 and 20, heat shock
      protein 27, smooth muscle protein 22 alpha, alpha-enolase, squamous cell
      carcinoma antigen 1 and 2, glutathione S-transferase and apolipoprotein a1) were
      protein previously known to be involved in tumor, and 21 proteins were newly
      identified in this study. CONCLUSION: 2-DE offers the total protein expression
      profiles of SCC tissues; further characterization of these differentially
      expressed proteins will give a chance to identify the badly needed tumor-specific
      diagnostic markers for SCC.

PMID- 19771268
TI  - Hydrogen peroxide producing lactobacilli in women with cervical neoplasia.
AB  - PURPOSE: It is well known that human papillomavirus (HPV) is the main cause of
      cervical neoplasia, and hydrogen peroxide-producing lactobacilli are the most
      important microorganisms for maintaining the balance of the vaginal ecosystem.
      The purpose of our study was to investigate the relationship of hydrogen peroxide
      producing lactobacilli, cervical neoplasia and high-risk HPV. MATERIALS AND
      METHODS: We enrolled 1138 women with abnormal cervical smears or cervicograms who
      were referred to the department of Obstetrics and Gynecology at Chonnam National
      University Medical School. In all of them, 1,138 vaginal swabs were collected for
      the qualitative assay of hydrogen peroxide producing lactobacilli and 150
      cervical swabs were used for the HPV hybrid capture II test without regard to the
      subjects' pregnancy status. In the non-pregnant women, 880 cervical biopsies
      and/or loop electrosurgical excision procedures were performed for making the
      histological diagnosis. RESULTS: There was no significant difference not only
      between the distribution of H(2)O(2) producing lactobacilli and the cervical
      histology, but also between the distribution of H(2)O(2) producing lactobacilli
      and the positivity for high-risk HPV. CONCLUSIONS: Both cervical neoplasia and
      high-risk HPV may not be influenced by the existence of hydrogen peroxide
      producing lactobacilli in the vagina.

PMID- 19771270
TI  - A case of recurrent solid pseudopapillary tumor of the pancreas with involvement
      of the spleen and kidney.
AB  - Solid pseudopapillary tumor of the pancreas (SPTP) is a rare primary pancreatic
      tumor of an unknown etiology that is usually diagnosed in adolescent girls and
      young women. Most SPTPs are considered to be benign and only rarely metastasize.
      We report here on a 27-year old woman with recurrent SPTP with involvement of
      both the spleen and left kidney at the time of the initial diagnosis, and with
      aggressive behavior. In July 1995, she was admitted with abdominal discomfort and
      mass. She underwent exploratory laparotomy with distal pancreatectomy, left
      nephrectomy and splenectomy, and was diagnosed with SPTP with invasion to both
      the spleen and left kidney. In June 2001, she again presented with abdominal pain
      and was diagnosed as having recurrence of the tumor. She underwent mass excision
      and omentectomy. Then she was lost to follow-up. In November 2005, she presented
      once again with an abdominal mass and was diagnosed with recurred SPTP, which
      formed a huge intraperitoneal mass with peritoneal seeding and the tumor showed
      multiple metastases in the liver. She is currently being treated conservatively.

PMID- 19771269
TI  - Augmentation of sodium butyrate-induced apoptosis by phosphatidylinositol 3
      kinase inhibition in the human cervical cancer cell-line.
AB  - PURPOSE: Sodium butyrate (NaBT) is principally a histone deacetylase (HDAC)
      inhibitor, and it has the potential to arrest HPV-positive carcinoma cells at the
      G1 to S phase transition of the cell cycle. The aim of study was to determine
      whether phosphatidylinositol 3-kinase (PI3K) inhibition can enhance the
      inhibitory effect of NaBT on a human cervical cancer cell line (HeLa). MATERIALS
      AND METHODS: Cervical cancer cells (HeLa) were treated with NaBT alone or in
      combination with the PI3K inhibitors wortmannin or LY294002. Cell viability
      analysis and FACS analysis were carried out. The expressions of the cell cycle
      related proteins were evaluated by Western-blot analysis. RESULTS: Inhibition of
      PI3K enhanced NaBT-mediated apoptosis and this decreased the HeLa cell viability.
      Either wortmannin or LY294002, combined with NaBT, enhanced the activation of
      caspase 3 and caspase 9, and this enhanced the subsequent cleavage of poly (ADP
      ribose) polymerase (PARP). Cervical cancer cells were arrested in the subG1 and
      G2/M phase, as was detected by FACS analysis. NaBT treatment in combination with
      PI3K inhibitors showed the increased expression of the CDK inhibitors
      p21(Cip1/Waf1) and p27(Kip1), in a p53 dependent manner, and also the increased
      dephosphorylation of Rb whereas there was a reduction in the expression levels of
      cyclin A, cyclin D1 and cyclin B1. CONCLUSION: The results demonstrate that
      inhibition of PI3K enhances NaBT-mediated cervical cancer cell apoptosis through
      the activation of the caspase pathway. Moreover, these findings will support
      future investigation using the PI3K inhibitors in combination with adjuvant
      treatment for treating carcinoma of the cervix.

PMID- 19771271
TI  - A pilot study of cisplatin, irinotecan, leucovorin and 5-fluorouracil (PILF)
      combination chemotherapy for advanced gastric cancer.
AB  - PURPOSE: Irinotecan, in combination with leucovorin/5-fluorouracil (FU) or with
      cisplatin, is known to be active for treating advanced gastric cancer (AGC). This
      pilot study evaluated a novel three-drug combination of irinotecan, leucovorin/FU
      and cisplatin as a first-line treatment of AGC. The primary endpoint was to
      assess the feasibility in anticipation of conducting a larger phase II study.
      MATERIALS AND METHODS: Chemotherapy-naive AGC patients received irinotecan 150
      mg/m(2) on day 1, and leucovorin 200 mg/m(2) and a 22-h infusion of FU 1000
      mg/m(2) on days 1 and 2. Cisplatin 30 mg/m(2) was administered on day 2.
      Treatment was repeated every 2 weeks until disease progression or unacceptable
      toxicity. RESULTS: Of the 17 eligible patients, two patients had an ECOG
      performance status of 2 and their median age was 48 years (range: 31 to 69). A
      total of 117 chemotherapy cycles were delivered (median: 6, range: 1 to 12). The
      causes of treatment discontinuation were disease progression in 9 patients (53%),
      refusal (35%) and toxicity (12%). Although grade 3 or 4 neutropenia (41% of
      patients) was the major toxicity that required dose adjustments, only one episode
      of febrile neutropenia occurred. Grade 3 or 4 nausea and vomiting, diarrhea and
      fatigue were observed in 35%, 35% and 29% of patients, respectively. None of the
      patients died of toxicity during treatment. Of the 16 patients who were evaluable
      for response, 7 (44%) experienced a partial response. CONCLUSION: This novel
      multi-drug combination was tolerated well in patients with AGC. Based on the
      encouraging efficacy and tolerability, a randomized phase II study is ongoing in
      this disease setting.

PMID- 19771272
TI  - Effects of the expression of leptin and leptin receptor (OBR) on the prognosis of
      early-stage breast cancers.
AB  - PURPOSE: Obesity-related leptin and leptin receptor (OBR) have a relation to the
      development of cancer and metastasis and also the low survival rate for breast
      cancer patients. Leptin has been associated with increased aromatase activity and
      it displays functional cross-talk with estrogen. This study was designed to
      determine the relationship between the expression of leptin and OBR in breast
      cancer tissue and the prognosis of early-stage breast cancer patients, and
      especially for the tamoxifen-treated patients. MATERIALS AND METHODS: Ninety-five
      patients with early-stage breast cancer and who had undergone surgical treatment
      at Kyung Hee University Hospital between January 1994 and June 2004 were
      analyzed. The surgical specimens underwent immunohistochemical analysis for
      leptin and OBR. The patients' survival and clinical characteristics were obtained
      from the medical records. RESULTS: Of the 95 patients, 79 (83%) and 32 (33.7%)
      showed the expression of leptin and OBR in breast cancer tissue, respectively.
      The expression of leptin and OBR in breast cancer tissue was not significantly
      related to the clinicopathological characteristics, including obesity, the
      expression of hormonal receptor, the HER-2/neu expression, menopause, stage and
      the nuclear grade. The expression of leptin and OBR was not significantly related
      to the overall disease-free survival (DFS). For the tamoxifen-treated
      postmenopausal obese patients, the DFS of the leptin-positive group was higher
      than that of the leptin-negative group (p=0.017). CONCLUSION: The expression of
      leptin and OBR in breast cancer tissue may be not a prognostic factor for disease
      free survival of breast cancer patients. In the future, further studies are
      needed to determine whether leptin expression could be a predictive factor for
      tamoxifen therapy in the postmenopausal obese subgroup among the early breast
      cancer patients.

PMID- 19771273
TI  - Patterns of failure after postoperative radiation therapy for endometrial
      carcinoma.
AB  - PURPOSE: We tried to investigate the outcome and patterns of failure of
      endometrial cancer patients who were treated with surgery and postoperative
      radiation therapy (RT). MATERIALS AND METHODS: Eighty-three patients with
      endometrial cancer who received postoperative RT between May 1979 and August 2000
      were included in this retrospective study. Forty-one patients received total
      abdominal hysterectomy, 41 patients received Wertheim's operation and 1 underwent
      vaginal hysterectomy. Pelvic lymph node dissection or pelvic lymph node sampling
      was done in 56 patients and peritoneal cytology was done in 35. All the patients
      were staged according to 1988 FIGO (International Federation of Gynecology and
      Obstetrics) staging system; 2 were stage IA, 23 were stage IB, 20 were stage IC,
      4 were stage IIA, 5 were stage IIB, 9 were stage IIIA, 2 were stage IIIB and 18
      were stage IIIC. The histologic diagnoses were adenocarcinoma in seventy-four
      patients (89%). The histologic grades were Grade 1, 2 and 3 in 21 (25%), 43 (52%)
      and 10 (12%) patients, respectively. All the patients received external beam RT
      (EBRT) with a median dose of 5,040 cGy (range: 4,500 approximately 5,075 cGy) to
      the whole pelvis. Five patients with pathologically confirmed paraaortic lymph
      node metastasis received 4500 cGy to the paraaortic lymph nodes. Fifteen patients
      received low-dose intracavitary brachytherapy after their EBRT. A total dose of
      7,500 approximately 9,540 cGy (median dose: 8511) was prescribed to the vaginal
      surface. RESULTS: Overall, 11 patients (13%) experienced disease relapse: 4 with
      initial stage I or II disease and 7 with initial stage III disease. Among the 54
      stage I or II patients, 1 (2%) relapsed in the pelvis only, 2 (4%) relapsed in
      the vagina and distant organs, and 1 (2%) relapsed in the paraaortic lymph nodes
      (PANs). Among the 29 stage III patients, 1 (3%) relapsed in the vagina. The most
      common sites of failure for the stage III patients were the peritoneum (3
      patients, 10%), PANs (2 patients, 7%), and lung (2 patients, 7%). With a median
      follow-up period of 86 months, the overall survival (OS) and disease-free
      survival (DFS) rates at 5 years were 87% for both. The five-year DFS rate was
      93%, 100% and 74% for the stage I, II and III patients, respectively. Three
      patients experienced severe radiation-related late complications: RTOG (Radiation
      Therapy Oncology Group) grade 3 radiation cystitis was seen in one patient, and
      grade 3 bowel obstruction was seen in two patients. CONCLUSIONS: Postoperative RT
      was useful for controlling pelvic disease. The major patterns of failure for
      stage III patients were peritoneal seeding and distant metastasis. Selective use
      of whole abdominal radiotherapy or adjuvant chemotherapy may improve the
      therapeutic outcome of these patients.

PMID- 19771274
TI  - Occludin expression in brain tumors and its relevance to peritumoral edema and
      survival.
AB  - PURPOSE: Peritumoral brain edema (PTBE) is a serious causative factor that
      contributes the morbidity or mortality of brain tumors. The development of PTBE
      is influenced by many factors, including such tight junction proteins as
      occludin. We evaluated the PTBE volume and survival time with respect to the
      occludin expression in various pathological types of brain tumors. MATERIALS AND
      METHODS: Fresh-frozen specimens from sixty patients who had brain tumors were
      obtained during surgery and the tumors were confirmed pathologically. The
      occludin expression was investigated by Western blot analysis. The PTBE volume
      was measured by using preoperative magnetic resonance (MR) imaging, and the
      survival time in each patient was estimated retrospectively. RESULTS: Occludin
      was detected in 41 (68.3%) of the cases with brain tumors and it was not
      expressed in the other 19 (31.7%) cases. Although the lowest expression was
      revealed in high-grade gliomas, its expression was variable according to the
      pathology of the brain tumors (p>0.05). The difference of PTBE volume between
      occludin-positive and negative brain tumors was statistically significant
      (2072.46+/-328.73 mm(3) vs. 7452.42+/-1504.19 mm(3), respectively, p=0.002). The
      mean survival time was longer in the occludin-positive tumor group than in the
      occludin-negative group (38.63+/-1.57 months vs. 26.16+/-3.83 months,
      respectively; p=0.016). CONCLUSIONS: This study suggests that the occludin
      expression is highly correlated to the development of PTBE in brain tumors and it
      might be a prognostic indicator for patient survival.

PMID- 19771275
TI  - AKAP12alpha is associated with promoter methylation in lung cancer.
AB  - PURPOSE: Promoter methylation is an important mechanism for silencing tumor
      suppressor genes in cancer and it is a promising tool for the development of
      molecular biomarkers. The purpose of the present study was to investigate whether
      inactivation of the A Kinase Anchoring Protein 12 (AKAP12) gene is assoCiated
      with promoter methylation in lung cancer. MATERIALS AND METHODS: The AKAP12
      expression was examined by reverse transcription-polymerase chain reaction (RT
      PCR) in ten lung cancer cell lines. The methylation status of the AKAP12alpha
      promoter was analyzed by performing bisulfite sequencing analysis in ten lung
      cancer cell lines, twenty four lung tissues and matched normal tissues. RESULTS:
      The AKAP12alpha expression was reduced in 6 of 10 (60%) lung cancer cell lines,
      whereas the AKAP12beta expression was absent in 1 of 10 (10%) lung cancer cell
      lines. The AKAP12alpha expression was restored after treatment with the
      demethylating agent 5-aza-2'-deoxycytidine in three lung cancer cell lines.
      Methylation of CpG island 1 in the AKAP12alpha promoter was detected in 30% of
      the lung cancer cell lines, whereas methylation of CpG island 2 in the
      AKAP12alpha promoter was observed in the immortalized bronchial cell line and in
      all the lung cancer cell lines. In lung tumors, the CpG island 1 in the
      AKAP12alpha promoter was infrequently methylated. However, CpG island 2 in the
      AKAP12alpha promoter was highly methylated in lung tumors compared with the
      surrounding normal tissues, and this was statistically significant (p=0.0001).
      CONCLUSION: Our results suggest that inactivation of the AKAP12alpha expression
      is assoCiated with DNA methylation of the promoter region in lung cancer, and
      that AKAP12alpha may play an important role in lung cancer carcinogenesis.

PMID- 19771276
TI  - Inhibition of phorbol ester-induced mouse skin tumor promotion and COX-2
      expression by celecoxib: C/EBP as a potential molecular target.
AB  - PURPOSE: Inflammation acts as a driving force for the development of cancer.
      Multiple lines of evidence suggest that nonsteroidal anti-inflammatory drugs,
      especially those that specifically target cyclooxygenase-2 (COX-2), are effective
      in preventing certain cancers. The present study was aimed at investigating the
      antitumor promoting potential of celecoxib in chemically induced mouse skin
      tumorigenesis, as well as elucidating the underlying molecular mechanisms.
      MATERIALS AND METHODS: To study the antitumor promoting effects of celecoxib, we
      used the classical two-stage mouse skin tumorigenesis model that involves
      initiation with a single application of 7,12-dimethylbenz [alpha]anthracene
      (DMBA) followed by promotion with repeated applications of 12-O
      tetradecanoylphorbol-13-acetate (TPA). The effects of celecoxib on the expression
      of COX-2, vascular endothelial growth factor (VEGF), p65 and the different
      isoforms of CCAAT/enhancer binding protein (C/EBP) were examined by performing
      Western blot analysis. Electrophoretic mobility gel shift assay was used to
      examine the effects of celecoxib on the TPA-induced DNA binding activities of
      various transcription factors. RESULTS: Our study revealed that topical
      application of celecoxib (10micromol) significantly reduced the multiplicity of
      papillomas in DMBA-initiated and TPA-promoted mouse skin. Pretreatment with
      celecoxib also diminished the expression of COX-2 and VEGF in the mouse skin
      papillomas. Pretreatment with celecoxib attenuated DNA binding of transcription
      factor (C/EBP) in the TPA-stimulated mouse skin. Moreover, celecoxib suppressed
      the TPA-induced nuclear expression of C/EBPdelta, but not C/EBPbeta, in mouse
      skin in vivo. CONCLUSION: Our study demonstrates the inhibitory effects of
      celecoxib on mouse skin tumor promotion, which was associated with a decreased
      expression of COX-2 and VEGF, as well as inhibition of C/EBP activation.

PMID- 19771277
TI  - The synergism between Belotecan and cisplatin in gastric cancer.
AB  - PURPOSE: We wanted to demonstrate the anti-cancer effect and interaction between
      belotecan and cisplatin on gastric cancer cell line and we evaluated the
      mechanisms of this synergistic effect in vitro. MATERIALS AND METHODS: The growth
      inhibitory effect of belotocan and cisplatin against several gastric cancer cell
      lines (SNU-5, SNU-16 and SNU-601) was estimated by tetrazolium dye assay. The
      effect of a combination treatment was evaluated by the isobologram method. The
      biochemical mechanisms for the interaction between the drugs were analyzed by
      measuring the formation of DNA interstrand cross-links (ICLs) and DNA topo-I
      activity. RESULTS: Belotecan showed synergism with cisplatin for growth
      inhibitory effect on the gastric cancer cell lines SNU-5, and SNU-16, but this
      was subadditive on the SNU-601 cell line. The formation of DNA ICLs in SNU-16
      cells by cisplatin was increased by combination with belotecan, but this was not
      affected in SNU-601 cells. The topo-I inhibition by belotecan was enhanced at
      high concentrations of cisplatin in SNU-16, but not in SNU-601 cells. CONCLUSION:
      Belotecan and cisplatin show various combination effect against gastric cancer
      cells. The synergism between cisplatin and belotecan could be the result of one
      of the following mechanisms: the modulating effect of belotecan on the repair of
      cisplatin-induced DNA adducts and the enhancing effect of cisplatin on the
      belotecan-induced topo-I inhibitory effect.

PMID- 19771278
TI  - Cell cycle regulatory protein expression profiles by adenovirus p53 infection in
      human papilloma virus-associated cervical cancer cells.
AB  - PURPOSE: The tumor suppressor gene, p53, has been established as an essential
      component for the suppression of tumor cell growth. In this study, we
      investigated the time-course anticancer effects of adenoviral p53 (Adp53)
      infection on human ovarian cancer cells to provide insight into the molecular
      level understanding of the growth suppression mechanisms involved in Adp53
      mediated apoptosis and cell cycle arrest. MATERIALS AND METHODS: Three human
      cervical cancer cell lines (SiHa, CaSki, HeLa and HT3) were used. The effect of
      Adp53 infection was studied via cell count assay, cell cycle analysis, FACS,
      Western blot and macroarray assay. RESULTS: Adp53 exerts a significant role in
      suppressing cervical cancer cell growth. Adp53 also showed growth inhibitory
      effects in each cell line, and it induced apoptosis and cell cycle arrest. Adp53
      differentially regulated the expression of genes and proteins, and the gene
      expression profiles in the SiHa cells revealed that the p21, p53 and mdm2
      expressions were significantly up-regulated at 24 and 48 hr. Western blot shows
      that the p21 and p53 expression-levels were significantly increased after Adp53
      infection. In addition, in all cell lines, both the CDK4 and PCNA protein
      expression levels were decreased 48 h after Adp53 infection. Cell cycle arrest at
      the G1 phase was induced only in the SiHa and HeLa cells, suggesting that
      exogenous infection of Adp53 in cancer cells was significantly different from the
      other HPV-associated cervical cancer cells. CONCLUSION: Adp53 can inhibit
      cervical cancer cell growth through induction of apoptosis and cell cycle arrest,
      as well as through the regulation of the cell cycle-related proteins. The Adp53
      mediated apoptosis can be employed as an advanced strategy for developing
      preferential tumor cell-specific delivery.

PMID- 19771279
TI  - Neoadjuvant imatinib in locally advanced gastrointestinal stromal tumors of the
      stomach: report of three cases.
AB  - Neoadjuvant imatinib therapy used to treat locally advanced or metastatic
      gastrointestinal stromal tumors (GI ST) remains under active investigation. We
      studied three cases of locally advanced gastric GISTs treated with imatinib on a
      neoadjuvant basis, followed by a complete surgical resection. Three patients were
      diagnosed with locally advanced unresectable GIST of the stomach and were started
      on imatinib 400 mg/day. After the imatinib treatment, partial responses were
      achieved in all patients and the tumors were considered resectable. Surgical
      resection was done after 7, 11, and 8 months of imatinib therapy, respectively.
      In one case, a metastatic liver lesion was detected during the imatinib treatment
      using computed tomography scans, so the imatinib therapy was maintained for 11
      months postoperatively. In the other two patients without distant metastasis,
      imatinib treatment was not restarted after surgery. Mutational analysis revealed
      a mutation in exon 11 of the c-kit gene in two patients, and wild-type c-kit and
      PDGFRA in one patient. During pathology review of all three cases, we noted
      several features common to imatinib treatment. There was no evidence of tumor
      recurrence in all three patients at respective follow-up visits of 22, 15, and 7
      months. These results suggest that the neoadjuvant imatinib therapy is a
      potentially curative approach for selected patients with locally advanced GIST.

PMID- 19771280
TI  - Long-term survival after surgical resection for liver metastasis from gastric
      cancer: two case reports.
AB  - Surgical resection of colorectal cancer metastasis to the liver results in a 5
      year survival rate of around 40%. Liver metastasis from other cancers such as
      neuroendocrine carcinoma and genitourinary tumors are also treated effectively
      with combined liver resection. However, hepatic metastasectomy for liver tumor
      from gastric cancer hasn't been considered as a standard treatment, and the
      benefit for this treatment has not been established. We report here on two cases
      of gastrectomy and combined liver resection for synchronous liver metastasis
      without any evidence of other metastatic lesions, and these two patients have
      survived for more than 7 years without evidence of disease recurrence. In
      conclusion, for patients with hepatic metastasis from gastric cancer, combined
      surgical resection of the liver metastasis should be considered as a treatment
      option when metastasis to other sites can be excluded.

PMID- 19771281
TI  - The periodic health evaluation of elite athletes: a consensus statement from the
      International Olympic Committee.

PMID- 19771283
TI  - Symptomatic and functional responses to concentric-eccentric isokinetic versus
      eccentric-only isotonic exercise.
AB  - CONTEXT: Rehabilitation protocols involving eccentric resistance exercise
      performed with loading more than 100% concentric 1-repetition maximum are
      effective in increasing muscle function in both healthy and injured populations.
      The mode of eccentric exercise (isokinetic versus isotonic) may be an important
      factor in limiting symptoms of delayed-onset muscle soreness and in improving
      muscle function after training. OBJECTIVE: To compare functional and symptomatic
      responses after an eccentric-only (ECC) isotonic exercise protocol and after a
      combined concentric-eccentric (CON-ECC) isokinetic exercise protocol matched for
      total exercise volume. DESIGN: Observational study. SETTING: Controlled research
      laboratory. PATIENTS OR OTHER PARTICIPANTS: Twenty-four healthy, untrained,
      college-aged men (n = 12) and women (n = 12). INTERVENTION(S): Participants were
      randomly assigned to the ECC isotonic or CON-ECC isokinetic exercise group and
      performed a single bout of resistance exercise involving the elbow flexors. MAIN
      OUTCOME MEASURE(S): Measurements of elbow flexion and extension, isometric
      strength, and muscle point tenderness were obtained before exercise (baseline)
      and during follow-up sessions (days 2, 4, 7, and 14). Separate 1-way analyses of
      variance and repeated-measures analyses of variance were used to determine
      outcome differences. Tukey post hoc testing was performed when indicated.
      RESULTS: At baseline, no differences were present between groups for any measure.
      The ECC isotonic exercise protocol resulted in a 30% to 36% deficit in muscle
      strength, a 5% to 7% reduction in elbow flexion, and a 6% to 8% reduction in
      elbow extension at follow-up days 2 and 4 (P < .01). The CON-ECC isokinetic
      exercise protocol did not alter muscle strength or range of motion at any time
      when compared with baseline. Muscle point tenderness increased from baseline on
      days 2 and 4 in both groups (P < .05) but was not different between groups
      throughout the recovery period. CONCLUSIONS: Our results indicated more
      pronounced functional deficits occurred after a single bout of ECC isotonic
      exercise than with a CON-ECC isokinetic exercise protocol matched for training
      volume.

PMID- 19771282
TI  - Electrolyte and plasma changes after ingestion of pickle juice, water, and a
      common carbohydrate-electrolyte solution.
AB  - CONTEXT: Health care professionals advocate that athletes who are susceptible to
      exercise-associated muscle cramps (EAMCs) should moderately increase their fluid
      and electrolyte intake by drinking sport drinks. Some clinicians have also
      claimed drinking small volumes of pickle juice effectively relieves acute EAMCs,
      often alleviating them within 35 seconds. Others fear ingesting pickle juice will
      enhance dehydration-induced hypertonicity, thereby prolonging dehydration.
      OBJECTIVE: To determine if ingesting small quantities of pickle juice, a
      carbohydrate-electrolyte (CHO-e) drink, or water increases plasma electrolytes or
      other selected plasma variables. DESIGN: Crossover study. SETTING: Exercise
      physiology laboratory. PATIENTS OR OTHER PARTICIPANTS: Nine euhydrated, healthy
      men (age = 25 +/- 2 years, height = 179.4 +/- 7.2 cm, mass = 86.3 +/- 15.9 kg)
      completed the study. INTERVENTION(S): Resting blood samples were collected
      preingestion (-0.5 minutes); immediately postingestion (0 minutes); and at 1, 5,
      10, 15, 20, 25, 30, 45, and 60 minutes postingestion of 1 mL/kg body mass of
      pickle juice, CHO-e drink, or tap water. MAIN OUTCOME MEASURE(S): Plasma sodium
      concentration, plasma magnesium concentration, plasma calcium concentration,
      plasma potassium concentration, plasma osmolality, and changes in plasma volume
      were analyzed. Urine specific gravity, osmolality, and volume were also measured
      to characterize hydration status. RESULTS: Mean fluid intake was 86.3 +/- 16.7
      mL. Plasma sodium concentration, plasma magnesium concentration, plasma calcium
      concentration, plasma osmolality, and plasma volume did not change during the 60
      minutes after ingestion of each fluid (P >or= .05). Water ingestion slightly
      decreased plasma potassium concentration at 60 minutes (0.21 +/- 0.14 mg/dL [0.21
      +/- 0.14 mmol/L]; P <or= .05). CONCLUSIONS: At these volumes, ingestion of pickle
      juice and CHO-e drink did not cause substantial changes in plasma electrolyte
      concentrations, plasma osmolality, or plasma volume in rested, euhydrated men.
      Concern that ingesting these volumes of pickle juice might exacerbate an
      athlete's risk of dehydration-induced hypertonicity may be unwarranted. If EAMCs
      are caused by large electrolyte loss due to sweating, these volumes of pickle
      juice or CHO-e drink are unlikely to restore any deficit incurred by exercise.

PMID- 19771284
TI  - A comparison of whole-body vibration and resistance training on total work in the
      rotator cuff.
AB  - CONTEXT: Whole-body vibration machines are a relatively new technology being
      implemented in the athletic setting. Numerous authors have examined the proposed
      physiologic mechanisms of vibration therapy and performance outcomes. Changes
      have mainly been observed in the lower extremity after individual exercises, with
      minimal attention to the upper extremity and resistance training programs.
      OBJECTIVE: To examine the effects of a novel vibration intervention directed at
      the upper extremity as a precursor to a supervised, multijoint dynamic resistance
      training program. DESIGN: Randomized controlled trial. SETTING: National
      Collegiate Athletic Association Division IA institution. PATIENTS OR OTHER
      PARTICIPANTS: Thirteen female student-athletes were divided into the following 2
      treatment groups: (1) whole-body vibration and resistance training or (2)
      resistance training only. INTERVENTION(S): Participants in the vibration and
      resistance training group used an experimental vibration protocol of 2 x 60
      seconds at 4 mm and 50 Hz, in a modified push-up position, 3 times per week for
      10 weeks, just before their supervised resistance training session. MAIN OUTCOME
      MEASURE(S): Isokinetic total work measurements of the rotator cuff were collected
      at baseline and at week 5 and week 10. RESULTS: No differences were found between
      the treatment groups (P > .05). However, rotator cuff output across time
      increased in both groups (P < .05). CONCLUSIONS: Although findings did not differ
      between the groups, the use of whole-body vibration as a precursor to multijoint
      exercises warrants further investigation because of the current lack of
      literature on the topic. Our results indicate that indirectly strengthening the
      rotator cuff using a multijoint dynamic resistance training program is possible.

PMID- 19771285
TI  - Jogging kinematics after lumbar paraspinal muscle fatigue.
AB  - CONTEXT: Isolated lumbar paraspinal muscle fatigue causes lower extremity and
      postural control deficits. OBJECTIVE: To describe the change in body position
      during gait after fatiguing lumbar extension exercises in persons with recurrent
      episodes of low back pain compared with healthy controls. DESIGN: Case-control
      study. SETTING: Motion analysis laboratory. PATIENTS OR OTHER PARTICIPANTS:
      Twenty-five recreationally active participants with a history of recurrent
      episodes of low back pain, matched by sex, height, and mass with 25 healthy
      controls. INTERVENTION(S): We measured 3-dimensional lower extremity and trunk
      kinematics before and after fatiguing isometric lumbar paraspinal exercise. MAIN
      OUTCOME MEASURE(S): Measurements were taken while participants jogged on a custom
      built treadmill surrounded by a 10-camera motion analysis system. RESULTS: Group
      by-time interactions were observed for lumbar lordosis and trunk angles (P <
      .05). A reduced lumbar spine extension angle was noted, reflecting a loss of
      lordosis and an increase in trunk flexion angle, indicating increased forward
      trunk lean, in healthy controls after fatiguing lumbar extension exercise. In
      contrast, persons with a history of recurrent low back pain exhibited a slight
      increase in spine extension, indicating a slightly more lordotic position of the
      lumbar spine, and a decrease in trunk flexion angles after fatiguing exercise.
      Regardless of group, participants experienced, on average, greater peak hip
      extension after lumbar paraspinal fatigue. CONCLUSIONS: Small differences in
      response may represent a necessary adaptation used by persons with recurrent low
      back pain to preserve gait function by stabilizing the spine and preventing
      inappropriate trunk and lumbar spine positioning.

PMID- 19771286
TI  - An evaluation of an educational intervention in psychology of injury for athletic
      training students.
AB  - CONTEXT: "Psychosocial Intervention and Referral" is 1 of the 12 content areas in
      athletic training education programs, but knowledge gained and skill usage after
      an educational intervention in this area have never been evaluated. OBJECTIVE: To
      evaluate the effectiveness of an educational intervention in increasing
      psychology-of-injury knowledge and skill usage in athletic training students
      (ATSs). DESIGN: Observational study. SETTING: An accredited athletic training
      education program at a large Midwestern university. PATIENTS OR OTHER
      PARTICIPANTS: Participants included 26 ATSs divided into 2 groups: intervention
      group (4 men, 7 women; age = 21.4 +/- 0.67 years, grade point average = 3.37) and
      control group (7 men, 8 women; age = 21.5 +/- 3.8 years, grade point average =
      3.27). DATA COLLECTION AND ANALYSIS: All participants completed the Applied Sport
      Psychology for Athletic Trainers educational intervention. Psychology-of-injury
      knowledge tests and skill usage surveys were administered to all participants at
      the following intervals: baseline, intervention week 3, and intervention week 6.
      Retention tests were administered to intervention-group participants at 7 and 14
      weeks after intervention. Analysis techniques included mixed-model analysis of
      variance (ANOVA) and repeated-measures ANOVA. RESULTS: The Applied Sport
      Psychology for Athletic Trainers educational intervention effectively increased
      psychology-of-injury knowledge (29-point increase from baseline to intervention
      week 6; F(2,23) = 29.358, P < .001, eta(p) (2) = 0.719) and skill usage (50-point
      increase from baseline to intervention week 6; F(2,23) = 5.999, P = .008, eta(p)
      (2) = 0.343) in undergraduate ATSs. These increases were maintained at the 7-week
      and 14-week retention testing (P < .001 for both). CONCLUSIONS: This first
      attempt at evaluating an educational intervention designed to improve ATSs'
      knowledge and skill usage revealed that the intervention was effective. Although
      both knowledge and skill usage scores decreased by the end of the retention
      period, the scores were still higher than baseline scores, indicating that the
      intervention was effective.

PMID- 19771287
TI  - Eccentric hip muscle function in females with and without patellofemoral pain
      syndrome.
AB  - CONTEXT: Patellofemoral pain syndrome (PFPS) is a common knee condition in
      athletes. Recently, researchers have indicated that factors proximal to the knee,
      including hip muscle weakness and motor control impairment, contribute to the
      development of PFPS. However, no investigators have evaluated eccentric hip
      muscle function in people with PFPS. OBJECTIVE: To compare the eccentric hip
      muscle function between females with PFPS and a female control group. DESIGN:
      Cross-sectional study. SETTING: Musculoskeletal laboratory. PATIENTS OR OTHER
      PARTICIPANTS: two groups of females were studied: a group with PFPS (n = 10) and
      a group with no history of lower extremity injury or surgery (n = 10).
      INTERVENTION(S): Eccentric torque of the hip musculature was evaluated on an
      isokinetic dynamometer. MAIN OUTCOME MEASURE(S): Eccentric hip abduction,
      adduction, and external and internal rotation peak torque were measured and
      expressed as a percentage of body mass (Nm/kg x 100). We also evaluated eccentric
      hip adduction to abduction and internal to external rotation torque ratios. The
      peak torque value of 5 maximal eccentric contractions was used for calculation.
      Two-tailed, independent-samples t tests were used to compare torque results
      between groups. RESULTS: Participants with PFPS exhibited much lower eccentric
      hip abduction (t(18) = -2.917, P = .008) and adduction (t(18) = -2.764, P = .009)
      peak torque values than did their healthy counterparts. No differences in
      eccentric hip external (t(18) = 0.45, P = .96) or internal (t(18) = -0.742, P =
      .47) rotation peak torque values were detected between the groups. The eccentric
      hip adduction to abduction torque ratio was much higher in the PFPS group than in
      the control group (t(18) = 2.113, P = .04), but we found no difference in the
      eccentric hip internal to external rotation torque ratios between the 2 groups
      (t(18) = -0.932, P = .36). CONCLUSIONS: Participants with PFPS demonstrated lower
      eccentric hip abduction and adduction peak torque and higher eccentric adduction
      to abduction torque ratios when compared with control participants. Thus,
      clinicians should consider eccentric hip abduction strengthening exercises when
      developing rehabilitation programs for females with PFPS.

PMID- 19771288
TI  - Generalizability theory analysis of balance error scoring system reliability in
      healthy young adults.
AB  - CONTEXT: An assessment of postural control is commonly included in the clinical
      concussion evaluation. Previous investigators have demonstrated learning effects
      that may mask concussion-induced balance decrements. OBJECTIVE: To establish the
      test-retest reliability of the Balance Error Scoring System (BESS) and to provide
      recommendations that account for known learning effects. DESIGN: Test-retest
      generalizability study. SETTING: Balance research laboratory. PATIENTS OR OTHER
      PARTICIPANTS: Young adults (n = 48) free from injuries and illnesses known to
      affect balance. INTERVENTION(S): Each participant completed 5 BESS trials on each
      of the assessment dates, which were separated by 50 days. MAIN OUTCOME
      MEASURE(S): Total score of the BESS was used in a generalizability theory
      analysis to estimate the overall reliability of the BESS and that of each facet.
      A decision study was completed to estimate the number of days and trials needed
      to establish clinical reliability. RESULTS: The overall reliability of the BESS
      was G = 0.64. The test-retest reliability was improved when male (0.92) and
      female (0.91) participants were examined independently. Clinically acceptable
      reliability (greater than 0.80) was established when 3 BESS trials were
      administered in a single day or 2 trials were administered at different time
      points. CONCLUSIONS: Learning effects have been noted in individuals with no
      previous exposure to the BESS. Our findings indicate that clinicians should
      consider interpreting the mean score from 3 BESS administrations on a given
      occasion for both normative data comparison and pretest and posttest design. The
      multiple assessment technique yields clinically reliable scores and provides the
      sports medicine practitioner with accurate data for clinical decision making.

PMID- 19771289
TI  - Knee joint kinematics and kinetics during a lateral false-step maneuver.
AB  - CONTEXT: Cutting maneuvers have been implicated as a mechanism of noncontact
      anterior cruciate ligament (ACL) injuries in collegiate female basketball
      players. OBJECTIVE: To investigate knee kinematics and kinetics during running
      when the width of a single step, relative to the path of travel, was manipulated,
      a lateral false-step maneuver. DESIGN: Crossover design. SETTING: University
      biomechanics laboratory. PATIENTS OR OTHER PARTICIPANTS: Thirteen female
      collegiate basketball athletes (age = 19.7 +/- 1.1 years, height = 172.3 +/- 8.3
      cm, mass = 71.8 +/- 8.7 kg). INTERVENTION(S): Three conditions: normal straight
      ahead running, lateral false step of width 20% of body height, and lateral false
      step of width 35% of body height. MAIN OUTCOME MEASURE(S): Peak angles and
      internal moments for knee flexion, extension, abduction, adduction, internal
      rotation, and external rotation. RESULTS: Differences were noted among conditions
      in peak knee angles (flexion [P < .01], extension [P = .02], abduction [P < .01],
      and internal rotation [P < .01]) and peak internal knee moments (abduction [P <
      .01], adduction [P < .01], and internal rotation [P = .03]). The lateral false
      step of width 35% of body height was associated with larger peak flexion,
      abduction, and internal rotation angles and larger peak abduction, adduction, and
      internal rotation moments than normal running. Peak flexion and internal rotation
      angles were also larger for the lateral false step of width 20% of body height
      than for normal running, whereas peak extension angle was smaller. Peak internal
      rotation angle increased progressively with increasing step width. CONCLUSIONS:
      Performing a lateral false-step maneuver resulted in changes in knee kinematics
      and kinetics compared with normal running. The differences observed for lateral
      false steps were consistent with proposed mechanisms of ACL loading, suggesting
      that lateral false steps represent a hitherto neglected mechanism of noncontact
      ACL injury.

PMID- 19771290
TI  - Identifying relationships among lower extremity alignment characteristics.
AB  - CONTEXT: The relationship between lower extremity alignment and lower extremity
      injury risk remains poorly understood, perhaps because most authors have examined
      only individual or a select group of alignment variables. Examining the
      relationships among alignment variables may allow us to more accurately describe
      lower extremity posture and clarify the relationship between lower extremity
      alignment and injury risk in future studies. OBJECTIVE: To measure lower
      extremity alignment variables and examine whether relationships could be
      identified among these variables. DESIGN: Observational study. SETTING:
      Laboratory. PATIENTS OR OTHER PARTICIPANTS: Two hundred eighteen (102 males: age
      = 23.1 +/- 3.2 years, height = 177.3 +/- 8.4 cm, mass = 80.8 +/- 13.0 kg; 116
      females: age = 21.8 +/- 2.7 years, height = 163.5 +/- 7.4 cm, mass = 63.4 +/-
      12.4 kg) healthy, college-aged participants. MAIN OUTCOME MEASURE(S): We measured
      pelvic angle, femoral anteversion, quadriceps angle, tibiofemoral angle, genu
      recurvatum, and tibial torsion to the nearest degree and navicular drop to the
      nearest millimeter on the right and left lower extremities. Separate principal
      components factor analyses were performed for each sex and side (left, right).
      RESULTS: A distinct lower extremity factor was identified, with relationships
      observed among increased pelvic angle, increased quadriceps angle, and increased
      tibiofemoral angle. A second distinct lower extremity factor was identified, with
      relationships observed among increased supine genu recurvatum, decreased tibial
      torsion, and increased navicular drop. Femoral anteversion loaded as an
      independent third factor. These distinct lower extremity alignment factors were
      consistent across side and sex. CONCLUSIONS: Factor analysis identified 3
      distinct lower extremity alignment factors that describe the potential
      interactions among lower extremity alignment variables. Future authors should
      examine how these collective alignment variables, both independently and in
      combination, influence dynamic knee function and risk for lower extremity
      injuries.

PMID- 19771291
TI  - Clinical assessment of scapular positioning in musicians: an intertester
      reliability study.
AB  - CONTEXT: The reliability of the measurement of the distance between the posterior
      border of the acromion and the wall and the reliability of the modified lateral
      scapular slide test have not been studied. Overall, the reliability of the
      clinical tools used to assess scapular positioning has not been studied in
      musicians. OBJECTIVE: To examine the intertester reliability of scapular
      observation and 2 clinical tests for the assessment of scapular positioning in
      musicians. DESIGN: Intertester reliability study. SETTING: University research
      laboratory. PATIENTS OR OTHER PARTICIPANTS: Thirty healthy student musicians at a
      single university. MAIN OUTCOME MEASURE(S): Two assessors performed a
      standardized observation protocol, the measurement of the distance between the
      posterior border of the acromion and the wall, and the modified lateral scapular
      slide test. Each assessor was blinded to the other's findings. RESULTS: The
      intertester reliability coefficients (kappa) for the observation in relaxed
      position, during unloaded movement, and during loaded movement were 0.41, 0.63,
      and 0.36, respectively. The kappa values for the observation of tilting and
      winging at rest were 0.48 and 0.42, respectively; during unloaded movement, the
      kappa values were 0.52 and 0.78, respectively; and with a 1-kg load, the kappa
      values were 0.24 and 0.50, respectively. The intraclass correlation coefficient
      (ICC) of the measurement of the acromial distance was 0.72 in relaxed position
      and 0.75 with the participant actively retracting both shoulders. The ICCs for
      the modified lateral scapular slide test varied between 0.63 and 0.58.
      CONCLUSIONS: Our results demonstrated that the modified lateral scapular slide
      test was not a reliable tool to assess scapular positioning in these
      participants. Our data indicated that scapular observation in the relaxed
      position and during unloaded abduction in the frontal plane was a reliable
      assessment tool. The reliability of the measurement of the distance between the
      posterior border of the acromion and the wall in healthy musicians was moderate.

PMID- 19771292
TI  - Strength profiles of shoulder rotators in healthy sport climbers and nonclimbers.
AB  - OBJECTIVE: To establish the isokinetic strength profiles and work ratios of the
      shoulder internal and external rotators in sport climbers and to compare them
      with these profiles and ratios in nonclimbers. We hypothesized that the strength
      profiles of the shoulder rotators were different between sport climbers and
      nonclimbers. DESIGN: Cross-sectional study. SETTING: Exercise science laboratory.
      PATIENTS OR OTHER PARTICIPANTS: Thirty-one experienced sport climbers and 27
      nonclimbers. MAIN OUTCOME MEASURE(S): We tested all participants by measuring the
      isokinetic concentric and eccentric work output of their shoulder rotators in the
      middle 110 degrees of shoulder rotation. We measured mean conventional work
      ratios of concentric external rotation (ER) to internal rotation (IR) (con ER:IR)
      and eccentric ER to IR (ecc ER:IR), and we measured mean functional work ratios
      of eccentric ER to concentric IR (ecc ER:con IR) and eccentric IR to concentric
      ER (ecc IR:con ER). RESULTS: All work ratios were different between the 2 groups
      (P < .001). In the climbers, the conventional work ratios were smaller than 1 for
      con ER:IR (0.79) and ecc ER:IR (0.88), whereas for the nonclimbers, the ratios
      were 1.03 and 1.13, respectively. The functional work ratio of ecc ER:con IR was
      smaller for the climbers (1.05) than for the nonclimbers (1.30), but the
      functional work ratio of ecc IR:con ER was larger for the climbers (1.58) than
      for the nonclimbers (1.17). CONCLUSIONS: The difference in work ratios of the
      shoulder rotators between participant groups might be due to training-induced
      changes in the shoulder rotation muscles of sport climbers. The clinical
      implication of this strength difference in shoulder IR and ER in climbers has yet
      to be examined.

PMID- 19771293
TI  - Topical silver for infected wounds.
AB  - REFERENCE/CITATION: Vermeulen H, van Hattem JM, Storm-Versloot MN, Ubbink DT.
      Topical silver for treating infected wounds. Cochrane Database Syst Rev.
      2007(1);CD005486. CLINICAL QUESTION: What is the clinical evidence base for
      silver dressings in the management of contaminated and infected acute and chronic
      wounds? DATA SOURCES: Investigations were identified by Cochrane Wounds Group
      Specialized Register (2006), CENTRAL (2006), MEDLINE (2002-2006), EMBASE (2002
      2006), CINAHL (2002-2006), and digital dissertations (2006) searches. Product
      manufacturers were contacted to identify additional eligible studies. The search
      terms included wound infection, surgical wound infection, ulcer, wound healing,
      and silver. STUDY SELECTION: Each study fulfilled the following criteria: (1) The
      study was a randomized controlled trial of human participants that compared
      dressings containing silver with any dressings without silver, dressings with
      other antiseptics, or dressings with different dosages of silver. (2) The
      participants were aged 18 years and older with contaminated and infected open
      wounds of any cause. (3) The study had to evaluate the effectiveness of the
      dressings using an objective measure of healing. No language or publication
      status restrictions were imposed, and participants could be recruited in any care
      setting. Studies were excluded if the wounds were ostomies (surgically formed
      passages). DATA EXTRACTION: Study quality assessment was conducted independently
      by 3 authors using the Dutch Institute for Health Care Improvement and Dutch
      Cochrane Centre protocols. Characteristics of the study, participants,
      interventions, and outcome measures were extracted by one author and verified by
      a second using a standard form. The principal outcome measure was healing (time
      to complete healing, rate of change in wound area and volume, number and
      proportion of wounds healed within trial period). Secondary measures were adverse
      events (eg, pain, maceration, erythema), dressing leakage, and wound odor. Based
      on the unique comparisons in the studies, a meta-analysis was not conducted. As a
      result, summary estimates of treatment effect were calculated for each outcome
      comparison. RevMan software (version 4.2; Cochrane Centre, Oxford, United
      Kingdom) was used for statistical analysis. MAIN RESULTS: Specific search
      criteria identified 31 studies for review, of which 3 met the inclusion and
      exclusion criteria. Lack of randomization and absence of wound infections
      excluded the majority of studies from the review. In the 3 studies selected,
      silver-containing dressings were compared with nonsilver dressings and dressings
      with other antimicrobials. One group used a silver-containing foam dressing and a
      nonsilver foam dressing; another group used a silver-containing alginate and a
      nonsilver alginate; and a third group used a silver-containing foam and various
      dressings (nonsilver foams, alginates, hydrocolloids, and gauze and other
      antimicrobial dressings). Sample sizes ranged between 99 and 619 participants.
      Most of the wounds in the included studies were pressure, diabetic, and venous
      leg ulcers. Wound infection was subjectively defined by 1 group as the presence
      of 2 or more signs and symptoms (eg, continuous pain, erythema, heat, or moderate
      to high levels of exudate) and by the other 2 groups as signs of critical
      colonization (eg, delayed healing, increased pain and exudate levels,
      discoloration, and odor). The primary measure in the included studies was healing
      outcome. The 3 groups used various assessments of healing, including relative and
      absolute reduction in wound area and number of wounds healed during the trial
      period. The trial period in each study was 4 weeks. In the 3 trials, the authors
      randomized the participants to the treatment groups. Examining healing, one group
      (129 participants) compared Contreet silver foam (Coloplast A/S, Humlebaek,
      Denmark) with Allevyn foam (Smith & Nephew, St-Laurent, Quebec, Canada). The
      authors reported no differences for rates of complete healing (risk difference
      [RD] = 0.00, 95% confidence interval [CI] = -0.09, 0.09) and median wound area
      reduction (weighted mean difference [WMD] = -0.30 cm(2), 95% CI = -2.92, 2.35).
      However, Contreet was favored over Allevyn (P = .034) for median relative
      reduction in wound area (WMD = -15.70 cm(2), 95% CI = -29.5, -1.90). One group
      (99 participants) compared Silvercel silver alginate (Johnson & Johnson Wound
      Management, Somerville, NJ) with Algosteril alginate (Johnson & Johnson Wound
      Management). The authors found no differences in rates of complete healing (RD =
      0.00, 95% CI = -0.06, 0.05), mean absolute (WMD = 4.50 cm(2), 95% CI = -0.93,
      9.93) and relative wound area reduction (WMD = -0.30 cm(2), 95% CI = -17.08,
      16.48), or healing rate per day (week 1 to 4) (WMD = 0.16 cm(2), 95% CI = -0.03,
      0.35). One group (619 participants) compared Contreet with various dressings
      (nonsilver foams, alginates, hydrocolloids, and gauze and other antimicrobial
      dressings). For median relative wound area reduction, the authors noted a
      superiority of Contreet over the various dressings (P = .0019). Examining
      secondary outcomes, 2 groups used subjective analysis to compare adverse
      reactions among the dressings. One group reported no difference between Contreet
      (in satellite ulcers, deterioration of periwound tissue) and Allevyn (in
      satellite ulcers, maceration, eczema) (RD = 0.02, 95% CI = -0.07, 0.12), and one
      group found no difference between Silvercel (in pain during dressing change,
      eczema, periwound erythema, maceration) and Algosteril (in pain during dressing
      change, eczema, erythema) (RD = -0.01, 95% CI = -0.12, 0.11). Two groups
      subjectively assessed leakage among silver and nonsilver dressings. The data from
      one group demonstrated superiority of Contreet over Allevyn (P = .002; RD = 
      0.30, 95% CI = -0.47, -0.13), and one group found Contreet better than various
      dressings (eg, nonsilver foams, alginates, hydrocolloids, and gauze, and other
      antimicrobial dressings) (P = .0005; RD = -0.11, 95% CI = -0.18, -0.05). Using a
      subjective 4-point scale, one group compared silver and nonsilver dressings and
      reported a difference favoring Contreet over Allevyn in terms of wound odor (P =
      .030; RD = -0.19, 95% CI = -0.36, -0.03). CONCLUSIONS: Overall, this review
      provides no clear evidence to support the use of silver-containing foam and
      alginate dressings in the management of infected chronic wounds for up to 4
      weeks. However, the use of silver foam dressings resulted in a greater reduction
      in wound size and more effective control of leakage and odor than did use of
      nonsilver dressings. Randomized controlled trials using standardized outcome
      measures and longer follow-up periods are needed to determine the most
      appropriate dressing for contaminated and infected acute and chronic wounds.

PMID- 19771294
TI  - Unilateral hypoglossal nerve injury in a collegiate wrestler: a case report.
AB  - OBJECTIVE: To introduce the case of a collegiate wrestler who suffered a
      traumatic unilateral hypoglossal nerve injury. This case presents the opportunity
      to discuss the diagnosis and treatment of a 20-year-old man with an injury to his
      right hypoglossal nerve. BACKGROUND: Injuries to the hypoglossal nerve (cranial
      nerve XII) are rare. Most reported cases are the result of malignancy, with
      traumatic causes less common. In this case, a collegiate wrestler struck his head
      on the wrestling mat during practice. No loss of consciousness occurred. The
      wrestler initially demonstrated signs and symptoms of a mild concussion, with
      dizziness and a headache. These concussion symptoms cleared quickly, but the
      athlete complained of difficulty swallowing (dysphagia) and demonstrated slurred
      speech (dysarthria). Also, his tongue deviated toward the right. No other
      neurologic deficits were observed. DIFFERENTIAL DIAGNOSIS: Occipital-cervical
      junction fracture, syringomyelia, malignancy, iatrogenic causes, cranial nerve
      injury. TREATMENT: After initial injury recognition, the athletic trainer placed
      the patient in a cervical collar and transported him to the emergency department.
      The patient received prednisone, and the emergency medicine physician ordered
      cervical spine plain radiographs, brain computed tomography, and brain and
      internal auditory canal magnetic resonance imaging. The physician consulted a
      neurologist, who managed the patient conservatively, with rest and no contact
      activity. The neurologist allowed the patient to participate in wrestling 7
      months after injury. UNIQUENESS: To our knowledge, no other reports of unilateral
      hypoglossal nerve injury from relatively low-energy trauma (including athletics)
      exist. CONCLUSIONS: Hypoglossal nerve injury should be considered in individuals
      with head injury who experience dysphagia and dysarthria. Athletes with head
      injuries require cranial nerve assessments.

PMID- 19771296
TI  - Goals, dreams and deadlines.

PMID- 19771297
TI  - Wake up call from 'Stars on the Ground'.

PMID- 19771298
TI  - Cough up for just a cup of coffee: Pharmacoeconomics of depression.

PMID- 19771295
TI  - The International Olympic Committee (IOC) consensus statement on periodic health
      evaluation of elite athletes: March 2009.

PMID- 19771299
TI  - Are we over-dependent on pharmacotherapy?

PMID- 19771300
TI  - The conscious access hypothesis: Explaining the consciousness.
AB  - The phenomenon of conscious awareness or consciousness is complicated but
      fascinating. Although this concept has intrigued the mankind since antiquity,
      exploration of consciousness from scientific perspectives is not very old. Among
      myriad of theories regarding nature, functions and mechanism of consciousness,
      off late, cognitive theories have received wider acceptance. One of the most
      exciting hypotheses in recent times has been the "conscious access hypotheses"
      based on the "global workspace model of consciousness". It underscores an
      important property of consciousness, the global access of information in cerebral
      cortex. Present article reviews the "conscious access hypothesis" in terms of its
      theoretical underpinnings as well as experimental supports it has received.

PMID- 19771301
TI  - Evaluation of antioxidant deficit in schizophrenia.
AB  - AIM: Oxidative stress is a state in which there is disequilibrium between pro
      oxidant processes and the antioxidant defense system in favor of the former and
      occurs as a consequence of increased production of free radicals or when the
      antioxidant defense system is inefficient or a combination of both events. A
      disturbance in the antioxidant defense system, including antioxidant enzymes
      superoxide dismutase (SOD) and glutathione peroxidase (GSHPx), due to free
      radical-induced oxidative injury has also been implicated in various
      neuropsychiatric disorders. Hence the role of these antioxidant enzymes and the
      changes in their level in blood and correlation with oxidative stress and the
      overall mechanism of defense were studied in a common psychiatric illness,
      schizophrenia. MATERIALS AND METHODS: Fifty subjects of either sex ranging in age
      from 18 to 60 years, divided into two age groups (< 40 years and >40 years),
      diagnosed for schizophrenia; and 50 age- and sex-matched normal subjects as
      controls were included in the study. Blood samples were collected for the
      determination of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione
      peroxidase (GSHPx), and reduced glutathione (GSH). RESULTS: Significantly lower
      levels of the two antioxidant enzymes were found in schizophrenics compared to
      normal controls, with an increased oxidative stress as indicated by high blood
      MDA levels. The condition worsened with advancing age, smoking, among literate
      masses, and in chronic schizophrenics; whereas gender did not show any effect.
      CONCLUSION: It can be concluded that an imbalance in the antioxidant defense
      system, along with enzymatic antioxidants, occurs in schizophrenia due to the
      persistent oxidative stress. Modern life style perhaps also contributes to the
      condition.

PMID- 19771302
TI  - Prevalence and pattern of mental disability using Indian disability evaluation
      assessment scale in a rural community of Karnataka.
AB  - BACKGROUND: In the present era, mental disability is a major public health
      problem in the society. Many of the mental disabilities are correctable if
      detected early. OBJECTIVES: To assess the prevalence and pattern of mental
      disability. SETTING AND DESIGN: Community-based cross-sectional study. One
      thousand subjects in all age groups were randomly selected from four villages in
      Udupi district, Karnataka. MATERIALS AND METHODS: The study was conducted by
      making house-to-house visits, interviewing, and examining all the individuals in
      the families selected with pre-designed and pretested questionnaire. STATISTICAL
      ANALYSIS: Proportions, chi-square test. RESULTS AND CONCLUSION: The prevalence of
      mental disability was found to be 2.3%. The prevalence was higher among females
      (3.1%) than among males (1.5%). The prevalence was higher among the elderly age
      group and illiterates. There is ample scope for community-based rehabilitation of
      the mentally disabled.

PMID- 19771303
TI  - A cross-sectional comparison of disability and quality of life in euthymic
      patients with bipolar affective or recurrent depressive disorder with and without
      comorbid chronic medical illness.
AB  - BACKGROUND: There are major health care implications of quality of life (QOL) and
      disability in long-standing disorders such as bipolar affective disorder (BAD)
      and recurrent depressive disorder (RDD). OBJECTIVES: To compare the inter-episode
      QOL and disability in patients with the diagnosis of BAD or RDD in remission with
      and without comorbid chronic medical illness. MATERIALS AND METHODS: Cross
      sectional assessments of the four groups were carried out. Euthymic bipolar or
      RDD subjects with chronic comorbid medical illnesses were included in the study.
      QOL assessment was carried out using the World Health Organization (WHO)-QOL -
      Bref Kannada version. Disability was assessed using the Schedule for Assessment
      of Psychiatric Disability (SAPD), which is an Indian modification of the WHO
      Disability Assessment Schedule-II. RESULTS: Eighty patients were enrolled into
      the study (20 patients in each group). The mean disability scores in the BAD
      group was significantly more in 'social role' (P = 0.038), and in the RDD group
      it was more in 'home atmosphere' (P = 0.001) in the two groups (n = 40) with
      chronic comorbid medical illness. In the other group without comorbid chronic
      medical illness (n = 40), the BAD group had significantly more disability in
      'overall behavior' (P = 0.002) and 'social role' (P = 0.001), and the RDD group
      had significantly more disability in 'assets and/or liabilities' (P = 0.004) and
      'home atmosphere' (P = 0.001). The QOL measures did not differ significantly
      between the two disorders. CONCLUSIONS: The presence of chronic comorbid medical
      illness did not cause a difference in the QOL between the two groups in periods
      of euthymia. However, disability measures differed significantly between the
      groups.

PMID- 19771304
TI  - Suicidal behavior amongst adolescent students in south Delhi.
AB  - OBJECTIVE: To study the prevalence of suicidal behavior and its epidemiological
      correlates amongst adolescent students in south Delhi. SETTINGS AND DESIGN: A
      cross-sectional study in three schools and two colleges in south Delhi.
      PARTICIPANTS: A total of 550 adolescent students aged 14 to 19 years selected by
      cluster sampling. STATISTICAL ANALYSIS: Proportions, chi square test, bivariate
      logistic regression. RESULTS: About 15.8% reported having thought of attempting
      suicide, while 28 (5.1%) had actually attempted suicide, both being more in
      females than in males. Statistically significant associations were observed with
      the age of the student, living status of parents, working status of mother, and
      whether the student was working part-time. The two variables found significant on
      multivariate analysis were female gender and the number of role models the
      student had ever seen smoking or drinking. CONCLUSION: The prevalence of suicide
      risk behavior was found to be quite high and is a matter that should evoke public
      health concern.

PMID- 19771305
TI  - Psychological autopsy of 101 suicide cases from northwest region of India.
AB  - BACKGROUND: The present study was conducted by the Department Of Psychiatry,
      Govt. Medical College and Hospital, Chandigarh, to investigate suicide cases
      during the year 2003. AIM: To assess the socio-demographic characteristics,
      psychosocial factors, and psychiatric and physical comorbidity associated with
      completed suicide. MATERIALS AND METHODS: One hundred one suicide cases were
      assessed using semi-structured proforma for recording socio-demographic profile,
      psychosocial variables, and treatment details. RESULTS: Majority (59.4%) of
      suicide victims were in the age group of 20 to 29 years. Males (57.4%) slightly
      outnumbered females (42.57%) in this study. As many as 57.4% of the subjects had
      migrated from other parts of India. Hanging was the most common method used by
      the suicide victims (72.2%). Psycho-social stressors were found in 61 (60.3%)
      suicide victims. Psychiatric illness was found in 34 cases (33.6%). However, out
      of them only 16 (48.5%) suicide victims sought treatment prior to the attempt. As
      many as 57.4% of the subjects had shown behavioral change before the suicidal
      attempt. CONCLUSIONS: Our study suggests that specific focus in suicide
      prevention strategies should be on migrant population.

PMID- 19771306
TI  - Experiences of stigma and discrimination endured by people suffering from
      schizophrenia.
AB  - OBJECTIVE: It is important to understand stigma in India, given its varied
      culture and mixture of rural and urban populations. Information from western
      literature cannot be applied without considering the sociocultural differences.
      AIMS: The research aimed to study the subjective experiences of stigma and
      discrimination undergone by people suffering from schizophrenia in rural and
      urban environments in India. SETTINGS AND DESIGN: Patients were selected from the
      outpatient services of six adult psychiatric units of the National Institute of
      Mental Health and Neurosciences (NIMHANS), India, and from the six outreach
      centers located in rural areas. MATERIALS AND METHOD: Two hundred patients
      diagnosed with schizophrenia were selected from rural and urban areas. The
      experiences of stigma and discrimination were assessed using a semi-structured
      instrument. STATISTICAL TECHNIQUES: Both quantitative and qualitative analyses
      were done. RESULTS: Significant differences were seen between rural and urban
      respondents. Urban respondents felt the need to hide their illness and avoided
      illness histories in job applications, whereas rural respondents experienced more
      ridicule, shame, and discrimination. The narratives provide direct views of
      patients, supporting the key findings. CONCLUSION: Mental health programs and
      policies need to be sensitive to the consumers' needs and to organize services
      and to effectively decrease stigma and discrimination.

PMID- 19771307
TI  - Serotonin transporter gene polymorphism and treatment response to serotonin
      reuptake inhibitor (escitalopram) in depression: An open pilot study.
AB  - BACKGROUND: Blocking of the serotonin transporter is the main mechanism of action
      of SSRIs; therefore, the gene encoding this protein is a strong candidate for a
      possible genetic influence on the treatment response. AIM: To evaluate
      relationship between serotonin transporter gene promoter region polymorphism and
      the efficacy of SSRI (escitalopram) treatment in depression. MATERIALS AND
      METHODS: Fifty-seven consecutive patients with unipolar depressive episode (DSM
      IV criteria) were genotyped for the SERT gene polymorphism and treated with
      escitalopram 20 mg/day. Weekly assessment (HAM-D-21) was made for treatment
      response up to 6 weeks. RESULTS: Significant (P > 0.0001) difference between
      groups (ll vs. ss or ls) in response to treatment by escitalopram was revealed by
      our study. However, no difference with respect to age, gender, or onset of
      illness was observed between genotype subgroups. CONCLUSION: The study suggests
      that serotonin transporter gene polymorphism may have an influence on the
      effectiveness of SSRI treatment in depressive disorders, irrespective of clinical
      variables. Further controlled studies are required to validate these results.

PMID- 19771308
TI  - Antidepressant-like activity of tramadol in mice.
AB  - OBJECTIVE: To evaluate antidepressant-like effect of tramadol in mice. MATERIALS
      AND METHODS: Tramadol was administered at three different doses (10, 20, and 40
      mg/kg, i.p.) once daily for 7 days to Swiss albino mice of either sex. The
      immobility period of control and drug-treated mice was recorded in forced swim
      test (FST). The antidepressant effect of tramadol was compared to that of
      fluoxetine (20 mg/kg, i.p.), administered for seven successive days. RESULTS:
      Tramadol produced significant antidepressant effect at all the three (10, 20, and
      40 mg/kg) doses, as indicated by reduction in immobility times of drug-treated
      mice compared to control mice. The efficacy of tramadol at doses of 10 and 20
      mg/kg was comparable to that of fluoxetine, but antidepressant activity in
      animals administered with tramadol 40 mg/kg was significantly less as compared to
      fluoxetine-pretreated mice. CONCLUSION: The results of the present study indicate
      antidepressant-like activity of tramadol.

PMID- 19771310
TI  - Levofloxacin-induced acute psychosis.
AB  - A wide range of drugs can cause mental status changes. Fluoroquinolones are one
      among them and are underrecognised.The CNS side effects of levofloxacin like
      headache, dizziness, restlessness, tremor, insomnia, hallucinations, convulsions,
      anxiety and depression are well documented. We report a rare case of middle aged
      diabetic male admitted to hospital with multiple infections who developed acute
      psychosis following levofloxacin administration.

PMID- 19771309
TI  - Hyperprolactinaemia with amisulpride.
AB  - Amisulpride, a substituted benzamide derivative, is a second-generation
      antipsychotic that preferentially binds to D2/D3 receptors in limbic rather than
      striatal structures. High dosage preferentially antagonizes postsynaptic
      receptors, resulting in reduced dopamine transmission; and low dosage blocks
      presynaptic receptors, resulting in enhanced transmission. Hyperprolactinaemia
      may occur in patients receiving amisulpride at low dose of 50 mg/day and results
      in galactorrhoea, amenorrhea and sexual dysfunction. The symptom ameliorates on
      withdrawing the drug, switching to non-prolactin-elevating drugs, and timely
      management with dopamine agonist.

PMID- 19771311
TI  - Primary insomnia treated with Zolpidem in an 18-month-old child.
AB  - This report describes a case of an 18-month-old child who was treated for primary
      insomnia with Zolpidem. To the best of our knowledge, the published literature is
      devoid of any information on use of Zolpidem in infants and children.

PMID- 19771313
TI  - Private psychiatric care in the past: With special reference to Chennai.
AB  - The 'madhouse' managed by Connolly and Dalton, situated in Chennai, prior to the
      opening of the Madras Lunatic Asylum in 1871 is described. The status of the
      private madhouses of England that existed before the county asylums were
      established in 1845 is briefly touched upon. A legitimate criticism of the
      shortcomings of this system along with the need for reorganization was forcibly
      brought by writers such as Defoe and others. Their suggestions find a place in
      subsequent mental health legislations. The legislation covering these aspects
      incorporated in the Mental Health Act 1987 form the basis for the licensing of
      our private mental health care centres.

PMID- 19771312
TI  - Deficit schizophrenia: Concept and validity.

PMID- 19771314
TI  - As I lie sleepless this night......

PMID- 19771315
TI  - A pining.

PMID- 19771316
TI  - Reflex neurosis (NEAD).

PMID- 19771317
TI  - Carisoprodol-induced amnestic state.

PMID- 19771318
TI  - Non-compliance of prescriptions by the patients.

PMID- 19771319
TI  - Linkage between immunomodulation, neuroprotection and neurogenesis.
AB  - Neuronal protection and restoration are the major goals for the therapy of
      neurodegenerative diseases, representing a very active field of research. In
      multiple sclerosis, treatments need to target both the autoimmune inflammation
      and the pathological neurodegeneration. The optimal therapeutic approach may
      promote remyelination and axonal repair, and even lead to neuronal renewal. This
      review article will discuss both endogenous neuroprotective mechanisms and those
      triggered by potential therapies. Currently employed immunomodulatory treatments
      and their ability to induce neuroprotection, tissue repair and neurogenesis are
      also presented.

PMID- 19771321
TI  - Neuropeptides: relevance in treatment of depression and anxiety disorders.
AB  - The etiology and pathophysiology of both depression and anxiety remain unclear,
      but involve dysfunctional monoaminergic neurotransmission and function. The
      currently available antidepressant medications that work through optimizing the
      monoaminergic system are often limited by their lack of efficacy or their adverse
      effects. There is increasing evidence that some neuropeptides, including
      substance P, corticotropin-releasing factor, neuropeptide Y, vasopressin and
      galanin, may have relevance in both depression and anxiety. Integration of
      anatomical, physiological and clinical evidence suggests that modulation of
      monoaminergic transmission is the most likely mechanism by which neuropeptides
      may work in these disorders. These neuropeptides and their receptors may serve
      not only as potential therapeutic targets for treatment of depression and
      anxiety, but may also help enhance our understanding of the psychopathology of
      these two major psychiatric disorders.

PMID- 19771322
TI  - Amyloid-targeted therapeutics in Alzheimer's disease: use of human albumin in
      plasma exchange as a novel approach for Abeta mobilization.
AB  - A clinical investigation program was carried out to replace endogenous albumin of
      patients with mild to moderate Alzheimer's disease (AD) with 5% Human Albumin
      Grifols(R) through a plasma exchange (PE) schedule, in order to alter the dynamic
      equilibrium between albumin-bound Abeta in plasma and Abeta in cerebrospinal
      fluid. In a pilot proof-of-concept study, 7 patients underwent 6 PE in 3 weeks
      and 1 year of follow-up. Plasma Abeta determinations demonstrated a variation
      pattern in levels in relation with the PEs. Cognitive status scores (MMSE and
      ADAS-Cog) were more stable than expected. In a phase II clinical trial, 29
      patients were randomized into PEtreated and control groups with 1 year follow-up.
      Interim results point toward the occurrence of Abeta40 mobilization in the PE
      treated patients, who scored better in cognitive tests (differences at 9 months:
      2.5 in MMSE and 5.5 in ADAS-cog). These results suggest that a PE program with 5%
      Human Albumin Grifols may have a promising role in the treatment of mild to
      moderate AD.

PMID- 19771320
TI  - GCC signaling in colorectal cancer: Is colorectal cancer a paracrine deficiency
      syndrome?
AB  - Guanylyl cyclase C (GCC) is the receptor expressed by intestinal cells for the
      paracrine hormones guanylin and uroguanylin that coordinate mucosal homeostasis
      and its silencing contributes to intestinal transformation. It orchestrates
      proliferative and metabolic circuits by limiting the cell cycle and programming
      metabolic transitions central to regeneration along the crypt-villus axis. Mice
      deficient in GCC are more susceptible to colon cancer induced by germline
      mutations or carcinogens. Moreover, guanylin and uroguanylin are the most
      commonly lost gene products in colon cancer. The role of GCC as a tumor
      suppressor and the universal loss of its hormones in transformation suggest a
      paradigm in which colorectal cancer is a disease of paracrine hormone
      insufficiency. Indeed, GCC signaling reverses the tumorigenic phenotype of human
      colon cancer cells by regulating proliferation and metabolism. These data suggest
      a pathophysiological hypothesis in which GCC is a tumor suppressor coordinating
      proliferative homeostasis whose silencing through hormone loss initiates
      transformation. The correlative therapeutic hypothesis suggests that colorectal
      cancer is a disease of hormone insufficiency that can be prevented or treated by
      oral hormone replacement therapy employing GCC ligands.

PMID- 19771323
TI  - Pregnancy-associated plasma protein A: Has this biomarker crossed the boundary
      from research to clinical practice?
AB  - There is already a substantial body of evidence suggesting that pregnancy
      associated plasma protein A (PAPP-A) participates in the atherosclerotic process.
      In several studies, PAPP-A has been associated with the development of vascular
      injury. PAPP-A has been proposed as a marker of the presence and extent of
      atherosclerotic disease and high-risk vulnerable plaques. It has been suggested
      that PAPP-A could have a role in the risk stratification of subjects in different
      clinical settings. Controversy exists, however, regarding the ability of
      commercially available assays to measure total versus free PAPP-A. The
      determination of PAPP-A, particularly in the very early phases of an acute
      myocardial infarction, may have a complementary role to that of cardiac
      troponins. This article focuses on the role of PAPP-A as both a marker of risk
      and a pathogenic factor in atherosclerotic disease.

PMID- 19771324
TI  - Molecule of the Month. Denosumab.

PMID- 19771325
TI  - Current and Future Perspectives in Psychiatric Drug Discovery.
AB  - On March 12, 2009, the Society for Medicines Research held a 1-day meeting
      entitled Current and Future Perspectives in Psychiatric Drug Discovery at
      GlaxoSmithKline, Harlow, U.K. The meeting, organized by Wendy Alderton, Eric
      Karran and Simon Ward, brought together experts from industry and academia to
      review the current challenges in the treatment of depression, schizophrenia and
      addiction. Recent advances in the development of novel agents for the treatment
      of these diseases were also presented.

PMID- 19771328
TI  - The discovery and development of the green fluorescent protein, GFP.

PMID- 19771329
TI  - GFP: from jellyfish to the Nobel prize and beyond.
AB  - On December 10, 2008 Osamu Shimomura, Martin Chalfie and Roger Tsien were awarded
      the Nobel Prize in Chemistry for "the discovery and development of the green
      fluorescent protein, GFP". The path taken by this jellyfish protein to become one
      of the most useful tools in modern science and medicine is described. Osamu
      Shimomura painstakingly isolated GFP from hundreds of thousands of jellyfish,
      characterized the chromophore and elucidated the mechanism of Aequorean
      bioluminescence. Martin Chalfie expressed the protein in E. coli and C. elegans,
      and Roger Tsien developed a palette of fluorescent proteins that could be used in
      a myriad of applications.

PMID- 19771331
TI  - The photochemistry of fluorescent proteins: implications for their biological
      applications.
AB  - Green fluorescent protein from Aequorea victoria, its relatives and derivatives
      are ubiquitous in their use as biological probes. In this tutorial review, we
      discuss the photochemistry of this fascinating class of proteins and illustrate
      some of their advantages and drawbacks in a range of applications. In particular,
      we focus on the ionisation states of the chromophore and how they are affected by
      internal and external proton transfer. Light-induced reversible and irreversible
      events are discussed in terms of the underlying chromophore structure. These
      phenomena have an influence on the interpretation of FRET (Forster resonance
      energy transfer), FRAP (fluorescence recovery after photobleaching), as well as
      single molecule studies.

PMID- 19771330
TI  - Genetically encoded biosensors based on engineered fluorescent proteins.
AB  - Fluorescent proteins have revolutionized cell biology by allowing researchers to
      non-invasively peer into the inner workings of cells and organisms. While the
      most common applications of fluorescent proteins are to image expression,
      localization, and dynamics of protein chimeras, there is a growing interest in
      using fluorescent proteins to create biosensors for minimally invasive imaging of
      concentrations of ions and small molecules, the activity of enzymes, and changes
      in the conformation of proteins in living cells. This tutorial review provides an
      overview of the progress made in the development of fluorescent protein-based
      biosensors to date.

PMID- 19771332
TI  - The structure and function of fluorescent proteins.
AB  - The current complement of fluorescent proteins (FPs) contains color variants
      whose emission spectra span most of the visible spectrum, providing researchers
      with a versatile toolset of fluorescent probes for live cell imaging
      applications. FP family members generate their chromophores autocatalytically
      through a series of posttranslational modifications. The fluorescence
      characteristics of GFP-family members are influenced in important ways by the
      local microenvironment surrounding the chromophore. In this tutorial review, we
      first examine the molecular factors that influence the photophysical properties
      of FP family members and then briefly discuss some of the ways in which these
      fascinating proteins have been applied to the field of live cell imaging.

PMID- 19771333
TI  - Green fluorescent protein: structure, folding and chromophore maturation.
AB  - The prolific use of green fluorescent protein and its variants throughout
      cellular biology relies on the post-translational formation of the chromophore,
      which proceeds without the need for any additional enzymes or cofactors, except
      molecular oxygen. In order to form the mature chromophore, the polypeptide
      backbone must undergo four distinct processes: folding, cyclisation, oxidation
      and dehydration. This tutorial review looks in detail at the proposed mechanisms
      for chromophore formation arising out of experimental and computational studies.
      The folding process is discussed, and the role that the native state plays in
      catalysing the initial cyclisation and subsequent chemistry is analysed. The
      specific functions of four conserved residues (Y66, G67, R96 and E222) in the
      maturation process are also presented. A greater understanding of the maturation
      process of fluorescent proteins from both jellyfish and coral species will profit
      the ongoing quest for brighter, faster maturing, genetically-encodable
      fluorescent probes of all colours, thus increasing their utility throughout the
      biomedical sciences.

PMID- 19771334
TI  - Visualization of molecular interactions using bimolecular fluorescence
      complementation analysis: characteristics of protein fragment complementation.
AB  - Investigations of the molecular processes that sustain life must include studies
      of these processes in their normal cellular environment. The bimolecular
      fluorescence complementation (BiFC) assay provides an approach for the
      visualization of protein interactions and modifications in living cells. This
      assay is based on the facilitated association of complementary fragments of a
      fluorescent protein that are fused to interaction partners. Complex formation by
      the interaction partners tethers the fluorescent protein fragments in proximity
      to each other, which can facilitate their association. The BiFC assay enables
      sensitive visualization of protein complexes with high spatial resolution. The
      temporal resolution of BiFC analysis is limited by the time required for
      fluorophore formation, as well as the stabilization of complexes by association
      of the fluorescent protein fragments. Many modifications and enhancements to the
      BiFC assay have been developed. The multicolor BiFC assay enables simultaneous
      visualization of multiple protein complexes in the same cell, and can be used to
      investigate competition among mutually exclusive interaction partners for complex
      formation in cells. The ubiquitin-mediated fluorescence complementation (UbFC)
      assay enables visualization of covalent ubiquitin family peptide conjugation to
      substrate proteins in cells. The BiFC assay can also be used to visualize protein
      binding to specific chromatin domains, as well as other molecular scaffolds in
      cells. BiFC analysis therefore provides a powerful approach for the visualization
      of a variety of processes that affect molecular proximity in living cells. The
      visualization of macromolecular interactions and modifications is of great
      importance owing to the central roles of proteins, nucleic acids and other
      macromolecular complexes in the regulation of cellular functions. This tutorial
      review describes the BiFC assay, and discusses the advantages and disadvantages
      of this experimental approach. The review will be of interest to scientists
      interested in the investigation of macromolecular interactions or modifications
      who need exquisite sensitivity for the detection of their complexes or conjugates
      of interest.

PMID- 19771336
TI  - Excited state reactions in fluorescent proteins.
AB  - The green fluorescent protein is a key technology in bioimaging. In this critical
      review, we consider how its various applications can be tailored from knowledge
      of the excited state chemistry. The photophysics of the basic chromophore in
      solution are described in detail, and the dominant radiationless decay mechanism
      is characterised. The quite different photophysics of wild type GFP are described
      next. The unique excited state proton transfer reaction observed can be used to
      model proton transfer processes in proteins. Examples where the proton transfer
      is blocked, or redirected to occur over a low short barrier H-bond are discussed.
      Finally the photophysics underlying the new generation of photochemically active
      fluorescent proteins are discussed (155 references).

PMID- 19771337
TI  - Photoreactions and dynamics of the green fluorescent protein.
AB  - The wild type green fluorescent protein (GFP) from Aequorea victoria has been
      extensively investigated with a strong focus on the photochemistry and structural
      dynamics that are linked with its diverse activities. GFP combines a number of
      remarkable, and some unique, features that are still intensely researched both
      experimentally and theoretically. The protein environment effectively inhibits
      deactivation pathways that are dominant in the isolated chromophore and is
      therefore responsible for the bright fluorescence. Its p-hydroxybenzylidene
      imidazolidinone chromophore acts as a photoacid, and optical excitation triggers
      ultrafast proton transfer reactions in the active site. The microscopic details
      of the proton transfer mechanism through a hydrogen bonding network are discussed
      in this critical review. This property of the wild type GFP has provided the
      opportunity to characterise the role of the specific protein environment in the
      proton transfer reactions in comparison to photoacid reactions in the condensed
      phase. In addition, GFP displays a photochromic side reaction that is uniquely
      caused by electron transfer from a buried anionic glutamic acid to the optically
      excited chromophore. This phototransformation property has also been exploited in
      high resolution fluorescence microscopy techniques. The discussion in this review
      is extended to include vibrational spectroscopy and structural dynamics (106
      references).

PMID- 19771338
TI  - The folding, stability and conformational dynamics of beta-barrel fluorescent
      proteins.
AB  - This critical review describes our current knowledge on the folding, stability
      and conformational dynamics of fluorescent proteins (FPs). The biophysical
      studies that have led to the elucidation of many of the key features of the
      complex energy landscape for folding for GFP and its variants are discussed.
      These illustrate some important issues surrounding how the large beta-barrel
      structure forms, and will be of interest to the protein folding community. In
      addition, the review highlights the importance of some of these results for the
      use of FPs in in vivo applications. The results should facilitate and aid in
      experimental designs of in vivo applications, as well as the interpretation of in
      vivo experimental data. The review is therefore of interest to all those working
      with FPs in vivo (103 references).

PMID- 19771343
TI  - Iron spin-crossover compounds: from fundamental studies to practical
      applications.
AB  - Over the past five years, the spin-crossover (SCO) phenomenon has experienced a
      clear new lease of interest from the scientific community coinciding with the
      recent publication of remarkable new advances. This perspective paper describes
      five illustrative examples of SCO systems, published during the past twelve
      months, showing new aspects of the unique and very appealing behaviour of these
      molecular switches, which may find interesting applications in the near future.

PMID- 19771345
TI  - Interaction of nitric oxide with gold nanoparticles capped with a ruthenium(II)
      complex.
AB  - Gold nanoparticles capped with a cis-(4
      aminothiophenol)bis(bipyridyl)(chloro)ruthenium(II) complex that are able to
      coordinate nitric oxide, become fluorescent and then liberate it by
      photolabilization when irradiated at 430 nm is reported.

PMID- 19771344
TI  - Metal complexes of amino acids and amino acid side chain groups. Structures and
      properties.
AB  - Alpha-amino acid residues exhibit various functions in biological systems. The
      side chain groups are very important for formation of the metal center and its
      catalytic action in proteins. They are involved in metal binding, molecular
      recognition by weak interactions, enzyme catalysis, and formation of the
      molecular environment. This perspective focuses on recent studies on
      characterization of metal-amino acid complexes involving imidazole, phenol,
      indole, or alkyl groups, their reactivities, and some selected metal-side chain
      group interactions.

PMID- 19771335
TI  - The fluorescent protein palette: tools for cellular imaging.
AB  - This critical review provides an overview of the continually expanding family of
      fluorescent proteins (FPs) that have become essential tools for studies of cell
      biology and physiology. Here, we describe the characteristics of the genetically
      encoded fluorescent markers that now span the visible spectrum from deep blue to
      deep red. We identify some of the novel FPs that have unusual characteristics
      that make them useful reporters of the dynamic behaviors of proteins inside
      cells, and describe how many different optical methods can be combined with the
      FPs to provide quantitative measurements in living systems (227 references).

PMID- 19771347
TI  - A mixed-valence diruthenium complex, triply bridged by mixed-moieties of chloro
      and methoxo ligands.
AB  - A mixed-valence diruthenium complex, whose metal centres were triply bridged by
      one chloro and two methoxo ligands, was synthesized and characterized by X-ray
      structural analysis, electrochemistry and spectroscopy, and its mixed-valence
      state was classified into Class III.

PMID- 19771346
TI  - Identification of the radiolytic product of hydrophobic ionic liquid
      [C4mim][NTf2] during removal of Sr2+ from aqueous solution.
AB  - SO(3)(2-) is identified as one of the radiolytic products of the ionic liquid 1
      butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([C(4)mim][NTf(2)])
      during the removal of strontium ions (Sr(2+)) from aqueous solution.

PMID- 19771348
TI  - Superoxide dismutase activity of corrole metal complexes.
AB  - The first report regarding SOD activity of metallocorroles, investigated via the
      combination of the cytochrome C assay, pulse radiolysis, and electrochemistry, is
      used for identifying the main criteria needed for achieving good performance, as
      well as for elucidating mechanistic aspects of their action.

PMID- 19771349
TI  - Phosphorus peri-bridged acenaphthenes: efficient syntheses, characterisation and
      quaternization reactions.
AB  - Using a novel strategy, tertiary phosphines based on single atom peri-bridged
      acenaphthenes were prepared and characterized by multinuclear NMR and by X-ray
      diffraction.

PMID- 19771350
TI  - Visible light driven room temperature Pauson-Khand reaction.
AB  - Visible light driven decarbonylation of [(mu(2)-alkyne)Co(2)(CO)(6)] complexes
      enables the formation of cyclopentenones in good yields at ambient temperatures.

PMID- 19771351
TI  - A visible light excitable fluorescent sensor for triphosphate/pyrophosphate based
      on a diZn2+ complex bearing an intramolecular charge transfer fluorophore.
AB  - Triphosphate or pyrophosphate can be recognised by a diZn(2+) complex of
      bis(BPEA)-appended intramolecular charge transfer fluorophore 4-amino-7
      aminosulfonyl-2,1,3-benzoxadiazole, displaying a 5-6 fold fluorescent enhancement
      at 576 nm.

PMID- 19771352
TI  - Bimetallic complexes based on carboxylate and xanthate ligands: synthesis and
      electrochemical investigations.
AB  - The homobimetallic ruthenium(II) and osmium(II) complexes
      [{RuR(CO)(PPh(3))(2)}(2)(S(2)COCH(2)C(6)H(4)CH(2)OCS(2))] (R = CH=CHBu(t),
      CH=CHC(6)H(4)Me-4, C(C[triple bond]CPh)=CHPh, CH=CHCPh(2)OH) and
      [{Os(CH=CHC(6)H(4)Me-4)(CO)(PPh(3))(2)}(2)(S(2)COCH(2)C(6)H(4)CH(2)OCS(2))] form
      readily from the reactions of [MRCl(CO)(BTD)(PPh(3))(2)] (M = Ru or Os; BTD =
      2,1,3-benzothiadiazole) with the dixanthate KS(2)COCH(2)C(6)H(4)CH(2)OCS(2)K.
      Addition of KS(2)COCH(2)C(6)H(4)CH(2)OCS(2)K to two equivalents of cis
      [RuCl(2)(dppm)(2)] leads to the formation of
      [{(dppm)(2)Ru}(2)(S(2)COCH(2)C(6)H(4)CH(2)OCS(2))](2+). The benzoate complexes
      [RuR{O(2)CC(6)H(4)(CH(2)OH)-4}(CO)(PPh(3))(2)] (R = CH=CHBu(t), CH=CHC(6)H(4)Me
      4, C(C[triple bond]CPh)=CHPh) are obtained by treatment of
      [RuRCl(CO)(BTD)(PPh(3))(2)] with 4-(hydroxymethyl)benzoic acid in the presence of
      base. Reaction of [RuHCl(CO)(PPh(3))(3)] or [RuRCl(CO)(BTD)(PPh(3))(2)] with 4
      (hydroxymethyl)benzoic acid in the absence of base leads to formation of the
      chloride analogue [RuCl{O(2)CC(6)H(4)(CH(2)OH)-4}(CO)(PPh(3))(2)]. The
      unsymmetrical complex [{Ru(CH=CHC(6)H(4)Me
      4)(CO)(PPh(3))(2)}(2)(O(2)CC(6)H(4)CH(2)OCS(2))] forms from the sequential
      treatment of [Ru(CH=CHC(6)H(4)Me-4){O(2)CC(6)H(4)(CH(2)OH)-4}(CO)(PPh(3))(2)]
      with base, CS(2) and [Ru(CH=CHC(6)H(4)Me-4)Cl(CO)(BTD)(PPh(3))(2)]. The new mixed
      donor xanthate-carboxylate ligand, KO(2)CC(6)H(4)CH(2)OCS(2)K is formed by
      treatment of 4-(hydroxymethyl)benzoic acid with excess KOH and two equivalents of
      carbon disulfide. This ligand reacts with two equivalents of [Ru(CH=CHC(6)H(4)Me
      4)Cl(BTD)(CO)(PPh(3))(2)] or cis-[RuCl(2)(dppm)(2)] to yield
      [{(dppm)(2)Ru}(2)(O(2)CC(6)H(4)CH(2)OCS(2))](2+) or [{Ru(CH=CHC(6)H(4)Me
      4)(CO)(PPh(3))(2)}(2)(O(2)CC(6)H(4)CH(2)OCS(2))], respectively. Electrochemical
      experiments are also reported in which communication between the metal centres is
      investigated.

PMID- 19771354
TI  - Calixarene-monophosphines as supramolecular chelators.
AB  - The calix[4]arenes 5-diphenylphosphino-17-R1-11,23-diR2-25,26,27,28
      tetrapropoxycalix[4]arene (1, R1 = R2 = Br; 2, R1 = Br, R2 = H; 3, R1 = R2 = p
      tolyl; 4, R1 = p-tolyl, R2 = H; 5, R1 = R2 = H; 20, R1 = p-tolyl, R2 = H), all
      bearing a diphenylphosphino group attached to the calixarene upper rim, have been
      synthesised starting from 5,11,17,23-tetrabromo-25,26,27,28
      tetrapropoxycalix[4]arene. Reaction of 1-5 with [RuCl2(p-cymene)]2 leads
      quantitatively to monophosphine complexes, [RuCl2(p-cymene)L], in which the endo
      oriented ruthenium atom unit sits inside the cone delineated by the four phenoxy
      rings. The particular orientation of the P-Ru vector appears to result from pi-pi
      interactions between the p-cymene ligand and two aromatic cavity walls. Overall,
      in each case the calixarene end of the ligand behaves as a supramolecular
      receptor towards the Ru(p-cymene) fragment. Formation of complexes with exo
      oriented P-M bonds were observed in the complexes cis-[PtCl2 x 1(2)] and in
      [RuCl2(p-cymene) x 20]. As shown by a variable temperature study carried out on
      [RuCl2(p-cymene) x 3], in which the ruthenium is embedded in an expanded cone,
      the p-cymene ring undergoes a fast oscillation about the Ru-arene bond which can
      be frozen out at low temperatures. Reaction of [RuCl2(p-cymene) x 3] with AgBF4
      in CH3CN results in an intra-cavity reaction, with one chloride ligand being
      replaced by acetonitrile.

PMID- 19771353
TI  - Bis- and tris(pyridyl)amine-oxidovanadium complexes: characteristics and insulin
      mimetic potential.
AB  - Two novel vanadium complexes, [V(IV)O(bp-O)(HSO4)] (1) and [V(IV)O(bp-OH)Cl2] x
      CH3OH (2 x CH3OH), where bp-OH is 2-{[bis(pyrid-2-yl)methyl]amine}methylphenol,
      were prepared and structurally characterised. EPR spectra of methanol solutions
      of 2 suggest exchange of Cl- for CH3OH and partial conversion to [VO(bp
      OH)(CH3OH)3]2+. Speciation studies on the VO2+-bpOH system in a water/dmso
      mixture (4:1 v/v) revealed [VO(bp-O)(H2O)n]+ as the dominating species in the pH
      range 2-7. The insulin-mimetic properties of 1 and 2, [V(IV)O(SO4)tpa] (3),
      [V(IV)O(pic-trpMe)2] (5) and the new mixed-ligand complexes [V(V)O(pic
      trpH)tpa]Cl2 (4Cl2) and [V(V)O(pic-OEt)tpa]Cl2 (6Cl2), tpa = tris(pyrid-2
      yl)methylamine, picH-trpH = 2-carboxypyridine-5-(L-tryptophan)carboxamide (picH
      trpMe is the respective tryptophanmethyl ester), pic-OEt = 5-carboethoxypyridine
      2-carboxylic acid, were evaluated with rat adipocytes, employing two lipolysis
      assays (release of glycerol and free fatty acids (FFA)), respectively and a
      lipogenesis assay (incorporation of glucose into lipids). The IC50 values for the
      inhibition of lipolysis in the FFA assay vary between 0.41 (+/-0.03) (5) and 21.2
      (+/-0.6) mM (2), as compared to 0.81 (+/-0.2) mM for VOSO4.

PMID- 19771355
TI  - Synthesis and X-ray characterization of [RhCl(C2H4)(PiPr3)]2. Multinuclear NMR
      and DFT investigation of its solid-state and solution reaction with dihydrogen.
      Ethene and propene hydrogenation by the solid Rh-hydrides.
AB  - [RhCl(C(2)H(4))(PiPr(3))](2) has been synthesised and structurally characterised.
      It shows an unusual planar Rh(2)Cl(2) system, with the two phosphine and the two
      ethene molecules disposed trans to each other. It easily reacts with dihydrogen
      in solution and in the solid state to afford ethane and a dimeric complex of
      formula [RhCl(H)(2)P](2). The latter exhibits a high fluxionality both in
      solution and in the solid state making impossible the identification of a single
      limiting structure even at 183 K. 25 different hydride structures are possible,
      four of which have very low interconversion barriers (1-3 kcal mol(-1)) and
      cannot be blocked even at 183 K. A multinuclear NMR study and HECTOR experiments
      have allowed to identify the most probable structures that interconvert at 198 K.
      The solid hydrides are able to hydrogenate quite selectively ethene and propene
      at room temperature. A TON higher than 5600 and a TOF of 97 h(-1) was observed
      with ethene (for propene the values were 5200 and 79, respectively). Toluene was
      hydrogenated to methylcyclohexane at 323 K under an atmospheric pressure of H(2)
      with a TOF h(-1) equal to 15.

PMID- 19771356
TI  - The metal-binding sites of glycose phosphates.
AB  - In aqueous solution, the reducing sugar phosphates D-arabinose 5-phosphate, D
      ribose 5-phosphate, D-fructose 1,6-bisphosphate, D-fructose 6-phosphate, D
      glucose 6-phosphate and D-mannose 6-phosphate provide metal-binding sites at
      their glycose core on reaction with Pd(II)(en) or M(III)(tacn) residues (M = Ga,
      Co; en = ethylenediamine, tacn = 1,4,7-triazacyclononane). The individual species
      were detected by one- and two-dimensional NMR spectroscopy. The coordination
      patterns are related to the metal-binding modes of the respective parent
      glycoses. In detail, ribo- and arabinofuranose phosphate favour kappaO(1,3)
      coordination, whereas the ketofuranose core of fructose phosphate and fructose
      bisphosphate provides the kappaO(2,3) chelator thus maintaining the configuration
      of the respective major solution anomer. On palladium excess, D-fructose 6
      phosphate is metallated twice in a unique kappaO(1,3):kappaO(2,4) metallation
      pattern. Dimetallation is also found for the aldohexose phosphates. A mixed
      glycose-core-phosphate chelation was detected for Pd(II)(en) and M(III)(tacn)
      residues with M = Al, Ga in the pH range just above the physiological pH for the
      D-fructose 1,6-bisphosphate ligand. The results are discussed in relation to D
      fructose-1,6-bisphosphate-metabolism in class-II aldolases.

PMID- 19771357
TI  - The Zinc proteome: a tale of stability and functionality.
AB  - Zinc proteins constitute a very important portion of the large number of
      Metalloproteins currently known. However, contrary to what happens with
      biological systems containing Fe(II), Fe(III), Cu(II), Mn(II), Mn(III), Ni(II),
      Co(III) or other commonly found biologically relevant metal cofactors, the
      particular chemical properties of the Zn(II) ion mean that only a very small
      number of experimental techniques can be directly applied in the study of the
      metal coordination spheres present in Zinc proteins. The information obtainable
      from publicly available structural databases such as the Protein Data Bank can
      therefore be of particularly high significance to a better understanding of these
      proteins. In this study, we draw a detailed statistical portrait of the Zinc
      proteome by analysing the metal coordination spheres of the large number of X-ray
      crystallographic structures of Zinc proteins currently available on the Protein
      Data Bank. This data is further complemented with quantum mechanical calculations
      on the most common Zinc coordination spheres to evaluate the intrinsic
      thermodynamic stability of the several combinations of ligands on a generic and
      non-specific enzymatic environment, and with molecular electrostatic potential
      maps. These results provide useful insights into this difficult to characterize
      but very important Zn-containing subset of the proteome.

PMID- 19771358
TI  - Syntheses, structures, and photoluminescence of a series of silver(I) sulfonates
      with pyrazine derivatives.
AB  - In this paper, ten novel silver(I) sulfonates containing pyrazine derivatives,
      [Ag(L1)(Pyr)(H2O)] (1), [Ag(L1)(2,3-Pyr)] (2), [Ag(L1)(2,5-Pyr)] x H2O (3),
      [Ag(L1)(2,3,5-Pyr)] (4), [Ag(L1)(2,3,5,6-Pyr)] (5), [Ag(L2)(Pyr)] (6),
      [Ag(L2)(2,3-Pyr)] (7), [Ag(L2)(2,6-Pyr)] (8), [Ag(L2)(2-Pyr)] (9), and
      [Ag(L2)(2,5-Pyr)] x H2O (10) (L1 = 3-amino-4-methylbenzenesulfonate anion; L2 = 2
      amino-3,5-dimethylbenzenesulfonate anion; Pyr = pyrazine; 2-Pyr = 2
      methylpyrazine; 2,3-Pyr = 2,3-dimethylpyrazine; 2,6-Pyr = 2,6-dimethylpyrazine;
      2,5-Pyr = 2,5-dimethylpyrazine; 2,3,5-Pyr = 2,3,5-trimethylpyrazine; 2,3,5,6-Pyr
      = 2,3,5,6-tetramethylpyrazine), have been synthesized and characterized by
      elemental analyses, IR spectroscopy and X-ray crystallography. In 1 and 7, the
      silver(I) centers are linked by bridging pyrazine ligands to form one-dimensional
      (1D) chains. The silver(I) ions of the compounds 2-6 are bridged by pyrazine
      ligands and sulfonate anions to form 2D polymeric structures. Compounds 8-10 show
      3D structures with diamond topologies. These results indicate that the steric
      hindrance of the pyrazine derivatives and the sulfonate anions containing
      different substituting groups play important roles in the framework formation of
      the silver(I) polymers. In addition, the luminescent properties of these
      compounds are also discussed in detail.

PMID- 19771360
TI  - Coordination polymer changing its magnetic properties and colour by thermal
      decomposition: synthesis, structure and properties of new thiocyanato iron(II)
      coordination polymers based on 4,4'-bipyridine as ligand.
AB  - Thermal decomposition of the ligand-rich 1:2 precursor solvate (1:2 = ratio
      between metal and ligand) [{Fe(mu2-bipy-N,N')(NCS)2(H2O)2} x bipy]n (1I) (bipy =
      4,4-bipyridine) reported recently leads to the stepwise formation of two new
      intermediates: a ligand-rich solvate-free 1:2 compound of composition
      [Fe(NCS)2(bipy)2]n (2) and a ligand-deficient 1:1 compound of composition
      [Fe(NCS)2(bipy)]n (3). The thermal decomposition is accompanied by a colour
      change from red (1I), via orange (2) into yellow (3). In the crystal structure of
      2 the iron(II) cations are coordinated by four N atoms of bridging bipy ligands,
      which connect the metal centers into layers, and two terminal N-bonded
      thiocyanato anions within slightly distorted octahedra. In the crystal structure
      of 3 the iron(II) cations are coordinated by two N atoms of bridging bipy
      ligands, which are connected by the metal centers into chains, and two N atoms as
      well as two S atoms of mu-1,3 bridging thiocyanato anions within a slightly
      distorted octahedral geometry. The thiocyanato anions connect these chains into
      layers. Due to their connection mode of the metal centers, only for the latter
      compound can cooperative magnetic phenomena be expected. Magnetic measurements
      revealed two different magnetic properties: The 1:2 compounds 1I and 2 show Curie
      Weiss paramagnetism and the 1:1 compound 3 shows an antiferromagnetic ordering at
      T(N) = 5.5 K. The reversibility of water reintercalation in the solvent-free
      compound 2 was investigated and followed by UV-Vis spectroscopy. Herein a new
      polymorphic metastable modification 1II of the pristine precursor compound 1I was
      obtained and characterized by single crystal X-ray determination.

PMID- 19771359
TI  - Intra- and intermolecular interaction ECL study of novel ruthenium tris-bipyridyl
      complexes with different amine reductants.
AB  - A series of ruthenium(II) tris-bipyridyl complexes covalently linked with
      different amine reductants such as tripropylamine (TPrA), ethanolamine and
      diethanolamine for an electrochemiluminescence (ECL) system have been
      synthesized. Their ECL property at different working electrodes has been studied
      with and without the presence of TPrA, triethanolamine (TEOA) and 2
      (dibutylamino) ethanol (DBAE) as the coreactant, respectively. The results
      demonstrate that the conjugated ruthenium complex alone can generate ECL through
      intramolecular interaction at a relatively low concentration, while with
      intermolecular interaction the ECL intensity increases progressively and becomes
      increasingly dominant with increasing complex concentration. For the coreactant
      system ECL, the amine coreactant needed for the conjugate complexes can be
      significantly lowered in comparison with that of the well known
      [Ru(bpy)(3)](2+)/TPrA system. One amine substituent is better for the system in
      order to diminish the steric hindrance, and the intramolecular amine reductant
      employed should have a similar structure with that of the additive amine
      coreactant to achieve a good ECL performance, which can pave a new route to
      further improving the ECL efficiency and increase the sensitivity of detection
      through combining both intra- and intermolecular interaction.

PMID- 19771361
TI  - Decavanadate interactions with actin: cysteine oxidation and vanadyl formation.
AB  - Incubation of actin with decavanadate induces cysteine oxidation and
      oxidovanadium(IV) formation. The studies were performed combining kinetic with
      spectroscopic (NMR and EPR) methodologies. Although decavanadate is converted to
      labile oxovanadates, the rate of deoligomerization can be very slow (half-life
      time of 5.4 h, at 25 degrees C, with a first order kinetics), which effectively
      allows decavanadate to exist for some time under experimental conditions. It was
      observed that decavanadate inhibits F-actin-stimulated myosin ATPase activity
      with an IC(50) of 0.8 microM V(10) species, whereas 50 microM of vanadate or
      oxidovanadium(IV) only inhibits enzyme activity up to 25%. Moreover, from these
      three vanadium forms, only decavanadate induces the oxidation of the so called
      "fast" cysteines (or exposed cysteine, Cys-374) when the enzyme is in the
      polymerized and active form, F-actin, with an IC(50) of 1 microM V(10) species.
      Decavanadate exposition to F- and G-actin (monomeric form) promotes vanadate
      reduction since a typical EPR oxidovanadium(IV) spectrum was observed. Upon
      observation that V(10) reduces to oxidovanadium(IV), it is proposed that this
      cation interacts with G-actin (K(d) of 7.48 +/- 1.11 microM), and with F-actin
      (K(d) = 43.05 +/- 5.34 microM) with 1:1 and 4:1 stoichiometries, respectively, as
      observed by EPR upon protein titration with oxidovanadium(IV). The interaction of
      oxidovanadium(IV) with the protein may occur close to the ATP binding site of
      actin, eventually with lysine-336 and 3 water molecules.

PMID- 19771362
TI  - Intercalation of stable organic radicals into layered saponite clay.
AB  - 2-(3- and 4-N-methylpyridinium)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazol-1
      oxyl 3-N-oxide (abbreviated as m- and p-MPYNN), the butyl derivative (m- and p
      BuPYNN), 4-(N-ethylammonium)-2,2,5,5-tetramethylpiperidin-1-oxyl (ETEP) and
      N,N,N',N'-Tetramethyl-1,4-phenylenediamine radical cation (TMPD(+)) have been
      successfully intercalated into saponite clay. The amount of intercalated material
      has been determined via UV/VIS spectroscopy, elemental analysis and EPR
      spectroscopy, and the expansion of the layer distance from approximately 12.0 to
      ca. 15 A has been measured by X-ray powder diffraction. The magnetic properties
      of these materials, which result from the interplay of the modified
      intermolecular interactions between the guest species, and the additional
      interaction with the host lattice, have been characterized by magnetic
      susceptibility, EPR and solid state NMR measurements. While the (29)Si and (27)Al
      NMR spectra show little influence of the radical species on the local structural
      environments of the nuclei in the host lattice, the guest-host interaction
      manifests itself in significant line-broadening and (in some cases) resonance
      displacements of the (1)H NMR signals belonging to the molecular radical cations.
      In the case of TMPD(+) intercalates, the NMR and EPR data indicate predominant
      radical dimerization within the interlayer space.

PMID- 19771363
TI  - Synthesis and characterization of Sn(II), Pb(II) and Yb(II) complexes supported
      by [C(Ph(2)P=NSiMe3){6-(2-RC5H3N)}]2- or [CH(Ph2P=NSiMe3){6-(2-RC5H3N)}]- (R =
      3,5-dimethyl-1-pyrazolyl or iminophosphoranyl) ligands.
AB  - The synthesis and characterization of several tin(II), lead(II) and ytterbium(II)
      complexes supported by [C(Ph2P=NSiMe3){6-(2-RC5H3N)}]2- or [CH(Ph2P=NSiMe3){6-(2
      RC5H3N)}]- (R = 3,5-dimethyl-1-pyrazolyl or iminophosphoranyl) ligands are
      reported. Reaction of 2-R-6-{CH2P(Ph2)=NSiMe3}C5H3N with M[N(SiMe3)2]2 (M = Sn,
      Pb) generated tin(II) and lead(II) complexes [M{C(Ph2P=NSiMe3){6-(2-RC5H3N)}}]2
      [3, M = Sn, R = 3,5-dimethyl-1-pyrazolyl; 4, M = Pb, R = 3,5-dimethyl-1
      pyrazolyl; 9, M = Sn, R = Me3SiN=P(Ph2); 10, M = Pb, R = Me3SiN=P(Ph2)]. When R =
      p-MeC6H4N=P(Ph2), a N,N-chelate tin(II) complex, [Sn{2-{N(p-MeC6H4)=PPh2}-6
      {CHP(Ph2)=NSiMe3}}{N(SiMe3)2}] (11), was isolated. Treatment of 2-(Ph2P=NSiMe3)-6
      {CH2P(Ph2)=NSiMe3}C5H3N with Yb[N(SiMe3)2]2(DME) afforded N,N,N-chelale
      ytterbium(II) complex [Yb{2-{N(SiMe3)=PPh2}-6-{CHP(Ph2)=NSiMe3}}{N(SiMe3)2}]
      (12). The complexes were characterized by elemental analyses and multinuclear NMR
      spectroscopy. Complexes 3, 4 and 10-12 were further characterized by single
      crystal X-ray diffraction techniques.

PMID- 19771364
TI  - Density functional study of the water exchange reaction of the polyoxocation
      GeO4Al12(OH)24(H2O)12(8+) (K-GeAl12) in aqueous solution.
AB  - The water exchange reaction of the polyoxocation
      GeO(4)Al(12)(OH)(24)(H(2)O)(12)(8+) (K-GeAl(12)) in aqueous solution has been
      simulated by means of supermolecule density functional calculations. In the
      proposed dissociative pathway, the leaving water molecule in the first
      coordination sphere is dissociated from its coordinated aluminium, and via a
      transition state enters into the second coordination sphere. Our calculated
      results indicate that the polyoxocation K-GeAl(12) exchanges water in a
      dissociative way with a barrier height of 37.0 kJ mol(-1), and that the gas-phase
      model is not suitable to simulate the water exchange reaction of K-GeAl(12)
      because of the proton-transfer reaction. The calculated results on the
      transmission coefficients of the water exchange reactions of K-MAl(12) imply that
      the water exchange reactions of aluminium species with similar structures have
      close transmission coefficients, but the different charges of aluminium species
      have an important influence on the transmission coefficients, which may be the
      reason why K-MAl(12) polyoxocations with different reactivity have nearly the
      same water exchange rate constants.

PMID- 19771365
TI  - Synthesis of a one-dimensional coordination polymer containing pendant
      hydrosulfide groups.
AB  - In view of the recent interest in compounds containing M-SH units, an organotin
      hydrosulfide compound, Me2Sn(SH)(O2CMe) (1) was prepared by controlled hydrolysis
      of the diorganotin thioacetate. Under similar mild hydrolytic conditions the
      corresponding benzoate could not be isolated. Instead, the thiobenzoate complex,
      Me2Sn(SOCPh)2 (3) was obtained in excellent yields indicating that there was no
      hydrolysis. Both 1 and 3 were characterized by X-ray crystallography. Some
      properties of the polymeric compound 1, such as spectral, electrical conductivity
      and NLO response were also studied. The reactivity and properties were explained
      using density functional calculations.

PMID- 19771366
TI  - AM-6: a microporous one-dimensional ferromagnet.
AB  - The vanadosilicate zeolite AM-6 is shown by a combination of spectroscopic
      techniques (UV-vis, Raman, XPS, XAS and EPR) to contain linear chains of
      alternating V=O and V-O bonds. The V(IV) ions in these chains are
      ferromagnetically coupled, and an excellent fit a to the susceptibility data with
      a one-dimensional Heisenberg model is obtained with J = 0.66(1) cm(-1). AM-6 is
      thus the first reported example of a microporous material incorporating one
      dimensional ferromagnetic chains.

PMID- 19771367
TI  - Gadolinium(III) complexes of 1,4,7-triazacyclononane based picolinate ligands:
      simultaneous optimization of water exchange kinetics and electronic relaxation.
AB  - The two new tripodal picolinate H(3)ebpatcn (1-carboxyethyl-4,7-bis((6
      carboxypyridin-2-yl)methyl)-1,4,7-triazacyclononane) and H(4)pbpatcn (1
      methylphosphonic-acid-4,7-bis((6-carboxypyridin-2-yl)methyl)-1,4,7
      triazacyclononane) ligands based on the 1,4,7-triazacyclononane anchor were
      prepared and their lanthanide complexes were characterized by NMR, fluorescence
      and potentiometric studies. The [Gd(ebpatcn)(H(2)O)] complex displays a
      relaxivity of r(1) = 4.68 mM(-1) s(-1) at 45 MHz and 298 K, whereas r(1) = 4.55
      mM(-1) s(-1) was measured for [Gd(Hpbpatcn)(H(2)O)] under the same conditions.
      The modified scaffold of the ligands with respect to the previously reported
      H(3)bpatcn (1-(carboxymethyl)-4,7-bis[(6-carboxypyridin-2-yl)methyl]-1,4,7
      triazacyclononane) leads to an optimization of the properties of these gadolinium
      complexes. The replacement of an acetate binding group of the H(3)bpatcn ligand
      with a propionate group (H(3)ebpatcn) or a phosphonate group (H(4)pbpatcn) leads
      to a faster exchange rate of the coordinated water molecule in both mono-aquo
      gadolinium complexes. The resulting water exchange rate is optimized for the
      future design of high relaxivity macromolecular gadolinium based contrast agents
      with a value measured by O(17) NMRD of k(ex) = 34 x 10(6) s(-1) for
      [Gd(Hpbpatcn)(H(2)O)] falling in the range of optimum values of (30 to 50) x
      10(6) s(-1) predicted by the SBM theory. The water exchange rate k(ex)(298) = 86
      x 10(6) s(-1) of the complex [Gd(ebpatcn)(H(2)O)] is the fastest reported in the
      literature for a neutral complex with only one inner-sphere water molecule. The
      relatively high stability of these modified gadolinium complexes (pGd = 14.1 for
      Gd(pbpatcn) and 13.1 for Gd(ebpatcn)) is similar to that of the
      [Gd(bpatcn)(H(2)O)] complex (pGd = 13.6). The high luminescence efficiency is
      also retained for the terbium complex. However, whereas the longitudinal
      electronic spin relaxation time keeps a value for [Gd(ebpatcn)(H(2)O)], which is
      long enough not to affect the relaxivity in macromolecular complexes (transient
      ZFS amplitude Delta(2) [10(20) rad(2) s(-2)] = 0.39), the O(17) relaxation and
      the (1)H NMRD indicate a rather fast electron spin relaxation for the phosphonate
      containing complex (Delta(2) [10(20) rad(2) s(-2)] = 1.3).

PMID- 19771368
TI  - Acenaphthene-1,2-diimine chromium complexes.
AB  - The reaction of (dpp-BIAN)Mg(THF)3 (1) with anhydrous CrCl3 in THF at 80 degrees
      C affords the mixed chromium-magnesium complex (dpp-BIAN)Cr(mu-Cl)3Mg(THF)3 (2).
      The treatment of 2 with 1,4-dioxane causes the elimination of MgCl2 and the
      formation of dimeric [(dpp-BIAN)Cr(mu-Cl)(THF)]2 (3). The reaction of (dpp
      BIAN)Na2 with CrCl3 gives the chlorine-free compound [Na(THF)6][(dpp-BIAN)2Cr]
      (4). Paramagnetic complexes 2, 3 and 4 have been characterized by IR and
      electronic absorption spectroscopy. The magnetic susceptibilities of 2 and 4 have
      been determined in solution using Evans method. The molecular structures of 2-4
      have been established by single crystal X-ray analysis.

PMID- 19771369
TI  - Synthesis, structures and ring-opening polymerization studies of new zinc
      chloride and amide complexes supported by amidinate heteroscorpionate ligands.
AB  - The reaction of the heteroscorpionate lithium salts [Li(pbpamd)(THF)] [pbpamd =
      N,N'-diisopropylbis(3,5-dimethylpyrazol-1-yl)acetamidinate] and [Li(tbpamd)(THF)]
      [tbpamd = N-ethyl-N'-tert-butylbis(3,5-dimethylpyrazol-1-yl)acetamidinate] with 1
      equivalent of ZnCl2 in THF affords very high yields of the neutral
      heteroscorpionate chloride zinc complexes [ZnCl(NNN)] (NNN = pbpamd 1 and tbpamd
      2). Compound 1 was used as a convenient starting material for the synthesis of
      aromatic amide zinc compounds [Zn(NHAr)(pbpamd)], where NHAr = 4
      methylphenylamide (NH-4-MeC6H4) 3, 2,4,6-trimethylphenylamide (NH-2,4,6-Me3C6H2)
      4 and 2,6-diethylphenylamide (NH-2,6-Et2C6H3) 5, by the reaction of the
      corresponding aromatic primary amide lithium salts. Alternatively, aliphatic
      amide derivatives [Zn(NR2)(pbpamd)] (R = SiMe3 6, SiHMe2 7 and iPr 8) were
      cleanly prepared by reacting the amidine-heteroscorpionate compound Hpbpamd with
      the corresponding bis(amide) zinc complexes [Zn(NR2)2] (R = SiMe3, SiHMe2 and
      iPr). The single-crystal X-ray structures of complexes 2, 3 and 6 confirm a 4
      coordinate arrangement in all cases, with the zinc metal surrounded in a
      distorted tetrahedral geometry and the heteroscorpionate ligands arranged in a
      kappa3 coordination mode. Whereas aliphatic amide heteroscorpionates 6-8 can act
      as efficient single-component initiators for the ring-opening polymerization of
      epsilon-caprolactone at room temperature, aromatic amide derivatives were not
      capable of yielding polymers even at high temperature. Epsilon-caprolactone is
      polymerized within minutes to give medium-high molecular weight polymers under
      mild conditions and with narrow polydispersities (M(w)/M(n) = 1.26). Polymer end
      group analysis shows that the polymerization mediated by aliphatic amide zinc
      complexes is initiated by amide transfer to the monomer.

PMID- 19771371
TI  - Synthesis and structure of tri- and octaindium compounds.
AB  - The reactions of InCp* with alkali metal silanides M(thf)(n)SiRPh(2) (R = Me, Ph)
      resulted in the triindanate [(Ph(3)Si)(3)In-In-In(SiPh(3))](-) with a linear
      arrangement of In atoms and the octaindium clusters [(In(8)(SiPh(3))(8)](m-) (m =
      0, 2) amongst others, which were characterized by X-ray crystallography. The
      neutral cluster has a bisphenoidal core similar to that of B(8)Cl(8), whilst the
      anionic one adopts a distorted square antiprismatic structure. In addition, the
      tri- and octaindium compounds were studied by DFT calculations.

PMID- 19771370
TI  - Novel half-sandwich Ru(II)-hydroxamate complexes: synthesis, characterization and
      equilibrium study in aqueous solution.
AB  - Novel half-sandwich Ru(II)-benzohydroxamate complexes were synthesized.
      [Ru(eta(6)-p-cymene)(mu-bha)](2)Cl(2) (bhaH = benzohydroxamic acid) with (O,O)
      coordination of the ligand, was characterized by elemental analysis,
      spectroscopic ((1)H-NMR, IR) and ESI-MS methods. Replacement of the chloride of
      the precursor by CF(3)SO(3)(-) and reaction of the obtained [Ru(eta(6)-p
      cym)(acetone)(3)](CF(3)SO(3))(2) with bhaH affords [Ru(eta(6)-p-cymene)(mu
      bha)](2)(CF(3)SO(3))(2), the crystal and molecular structure of which has been
      determined by X-ray crystallography. In this complex, the first reported
      structure of an organometallic Ru(II)-hydroxamate, the carbonyl oxygens of the
      bha ligands coordinate to one of the Ru units and the hydroxamate oxygens bridge
      the two Ru atoms. Hydrolytic behaviour of [Ru(eta(6)-p-cym)Cl(x)(H(2)O)(3-x)]((2
      x)+) (x = 0-3) present in aqueous solution and its complex forming capabilities
      with N-methyl-acetohydroxamic acid (meahaH) were studied by pH-potentiometric,
      (1)H-NMR, UV-Vis and ESI-MS methods. Formation constants of the various species
      present in solution are reported. The data are consistent with the formation of
      the stable, monomeric [Ru(eta(6)-p-cym)(meaha)](+) as the major species at
      physiological pH.

PMID- 19771372
TI  - Time and position resolved in situ X-ray diffraction study of the hydrothermal
      conversion of gypsum monoliths to hydroxyapatite.
AB  - Time-resolved energy dispersive X-ray diffraction (EDXRD) data have been measured
      in situ from cast blocks of gypsum, CaSO(4) x 2 H(2)O, in the presence of
      reactive phosphate solutions under hydrothermal conditions (100 < or = T < or =
      180 degrees C) in order to understand the formation of hydroxyapatite monoliths,
      for applications such as in artificial bone or dental materials. Measurement of
      data in short (60 s) intervals has thus permitted information about the kinetics
      and mechanism of transformation of gypsum to hydroxyapatite to be obtained in a
      non-invasive way, avoiding the irreversible conversion of hydrous intermediate
      phases that would occur on quenching. At the lower temperatures used gypsum first
      converts to an amorphous intermediate phase during reaction, but as the
      temperature is raised to 130 degrees C and above, hydrothermal dehydration to the
      subhydrate CaSO(4) x 1/2 H(2)O always occurs before hydroxyapatite crystallises.
      The final crystal size of the hydroxyapatite is estimated from the peak
      broadening of the EDXRD data and this reveals an increase in crystal dimension
      with increasing reaction temperature. Comparing measurements from the surface and
      from the core of the blocks shows that an additional phosphate phase, CaHPO(4),
      is observed in the core at two temperatures and also that the crystal growth of
      hydroxyapatite does not penetrate the core of the block on the time scales we
      have investigated (up to 6 hours). The observations have important implications
      in the fabrication of hydroxyapatite monoliths from cast gypsum for applications,
      since the conversion via several intermediate phases may compromise the integrity
      and mechanical properties of the monoliths.

PMID- 19771373
TI  - Structural, thermal and photomagnetic properties of spin crossover [Fe(bpp)2]2+
      salts bearing [Cr(L)(ox)2]- anions.
AB  - This paper is divided into two parts: in the first part, the influence of solvate
      molecules on the magnetic properties of spin crossover salts of
      [Fe(bpp)(2)][Cr(L)(ox)(2)]ClO(4) x nS (bpp = 2,6-bis(pyrazol-3yl)pyridine; L =
      2,2'-bipyridine (bpy) or 1,10-phenanthroline (phen); ox = oxalate dianion; S =
      solvent) is analyzed. The second part is devoted to the photomagnetic properties
      of the previously reported [Fe(bpp)(2)][Cr(L)(ox)(2)](2) family of compounds. The
      study describes the crystal structure, differential scanning calorimetry (DSC)
      and magnetic properties of [Fe(bpp)(2)][Cr(bpy)(ox)(2)]ClO(4) x EtOH x 4 H(2)O
      (1) and [Fe(bpp)(2)][Cr(phen)(ox)(2)]ClO(4) x 1.5 EtOH x 4 H(2)O (2). Both salts
      are high-spin (HS) compounds. Desolvation of 1 yields a material exhibiting a
      gradual spin crossover that involves 50% of the Fe(2+) cations. Rehydration of
      this desolvated salt induces a significant increase in the low-spin (LS)
      population. Desolvation of 2 affords a material showing a more abrupt spin
      crossover with thermal hysteresis (T(1/2)(increasing) = 286 K and
      T(1/2)(decreasing) = 273 K). This material is not very sensitive to rehydration.
      The anhydrous compounds [Fe(bpp)(2)][Cr(bpy)(ox)(2)](2) (3) and
      [Fe(bpp)(2)][Cr(phen)(ox)(2)](2) (4) display some quantitative photomagnetic
      conversion with T(LIESST) values of 41 and 51 K, respectively. Kinetic parameters
      governing the photo-induced HS-LS relaxation process have been determined and
      used to reproduce the T(LIESST) curves.

PMID- 19771374
TI  - The reactivity of 1,1-dialkoxyalkanes with niobium and tantalum pentahalides.
      Formation of coordination compounds, C-H and C-C bond activation and the X-ray
      structure of the stable carboxonium species [Me(2)C=CHC(=OMe)Me][NbCl(5)(OMe)].
AB  - The reactions of the pentahalides NbX5 (X = Cl, Br) with the 1,1-dialkoxyalkanes
      CHR'(OEt)2 or 1,3-dioxolane yield the coordination adducts NbX5[kappa1
      (OEt)CHR'(OEt)] (X = Cl, R' = H, 2a; X = Br, R' = H, 2b; X = Cl, R' = Me, 2c; X =
      Br, R' = Me, 2d) or NbCl5(kappa1-right angle OCH2OCH2C right angle H2), 3,
      respectively. Compounds 2a-c and 3 are stable at room temperature, while 2d
      slowly converts into the alkoxide NbBr4[OCH(Me)OEt], 4. Room-temperature
      fragmentations are observed upon reacting CH2(OMe)2, CHMe(OMe)2 and CMe2(OMe)2
      with MX5 (M = Nb, Ta; X = Cl, Br). The complexes MX5[O(Me)(CH2X)], 5, and
      [MX3(OMe)2]2, 6, form selectively from MX5/CH2(OMe)2 (M = Nb, Ta; X = Cl, Br),
      while mixtures of [NbX4(OMe)]2 (X = Cl, 8a; X = Br, 8b) and organic halides are
      obtained from NbX5/CHMe(OMe)2. Instead, the reaction of NbCl5 with CMe2(OMe)2
      affords the stable carboxonium species [Me2C=CHC(=OMe)Me][NbCl5(OMe)], 7, as
      prevalent product. Furthermore, 1,1-dialkoxyalkanes are generally activated by
      MF5 (M = Nb, Ta) at room temperature: according to the cases, alcohols, ethers,
      esters and ketones have been detected in the reaction mixtures after hydrolysis.
      In agreement with NMR data, the carboxonium ion [Me2C=CHC(=OMe)Me]+ is produced
      from NbF5/CMe2(OMe)2. The complexes NbF5[OEt(Me)], 9a, and NbF5[O=CH(OEt)], 9b,
      obtained by addition of CH2(OEt)2 to NbF5, have been characterised by NMR
      spectroscopy. Trimethyl formate, CH(OMe)3, reacts with NbX5 (X = Cl, Br) with
      formation of the alkoxides 6 and 8, in admixture with NbX5[O=CH(OMe)] and MeX;
      otherwise, MF5[O=CH(OMe)] and MF5(OMe2) have been synthesised from MF5/CH(OMe)3
      (M = Nb, Ta). Complete screening of the organic fragments produced in the
      distinct reactions has been carried out by both GC-MS and NMR analyses on the
      reaction mixtures, after treatment with water. The solid state structures of the
      mixed halo-alkoxy complexes [TaX3(OMe)(mu-OMe)]2 (X = Cl, 6c; X = Br, 6d) and of
      the stable alkylated ketone containing species 7 have been ascertained by X-ray
      diffraction studies.

PMID- 19771375
TI  - Platinum(II) mediated C(sp3)-H activation of tetramethylthiourea.
AB  - The C-H activation of the methyl group of tetramethylthiourea by cis
      [PtL(2)(NO(3))(2)] (L = phosphine or N-heterocyclic carbene) has been
      investigated as a function of the ligand L. The presence of an electron
      withdrawing group on the tertiary phosphine was found to promote the process.
      Moreover, when an excess of nitrate anion is present in the reaction mixture, the
      rate of C-H bond activation is retarded, suggesting the key role of an
      unsaturated tri-coordinate Pt(II) species as intermediate.

PMID- 19771376
TI  - A novel copper(II) complex of a tripodal ligand with phenolate-phenol
      interligand, intramolecular hydrogen bonding.
AB  - A novel tripodal ligand with three different arms, viz., pyridine, phenol and an
      oxime and its copper(II) complex were synthesised. The X-ray crystal structure of
      the compound reveals that it is a dinuclear complex consisting of two copper(II)
      ions doubly bridged by two oximato groups in a trans arrangement. The complex
      contains unusual cis-axially coordinated phenolates as well as a novel
      interligand, intramolecular phenolate-phenol hydrogen bond. Variable-temperature
      magnetic susceptibility measurements revealed that the two copper(II) centers are
      strongly antiferromagnetically coupled, with the exchange coupling constant -2J =
      800(42) cm(-1) (H = -2J S(1) x S(2)) for the two interacting S = 1/2 centres. The
      complex yields an (1)H NMR spectrum in CD(3)CN solution at room temperature, with
      relatively sharp signals and rather small hyperfine shifts, evidencing that the
      antiferromagnetically coupled dinuclear core is maintained in solution.

PMID- 19771377
TI  - Mn(II) complexes containing the polypyridylic chiral ligand (-)
      pinene[5,6]bipyridine. Catalysts for oxidation reactions.
AB  - A series of mononuclear and dinuclear chiral manganese(II) complexes containing
      the neutral bidentate chiral nitrogen ligand (-)-pinene[5,6]bipyridine, (-)-L,
      were prepared from different manganese salts. The chirality in these complexes
      arises from the pinene ring that has been fused to the 5,6 positions of one
      pyridine group of the bipyridine ligand. These complexes have been characterized
      through analytical, spectroscopic (IR, UV/Vis, ESI-MS) and electrochemical
      techniques (cyclic voltammetry). Single X-ray structure analysis revealed a five
      coordinated Mn(II) ion in [{MnCl((-)-L)}2(mu-Cl)2] (2), [{Mn((-)-L)}2(mu
      OAc)3](PF6) (3) and [MnCl2(H2O)((-)-L)] (4) and a six-coordinated one in [MnCl2((
      )-L)2] (5), [Mn(CF3SO3)2((-)-L)2] (6) and [Mn(NO3)(H2O)((-)-L)2)](NO3) (7). The
      magnetic properties of the binuclear compounds 2 and 3 have been studied. Both
      compounds show a weak antiferromagnetic coupling (2, J = -0.22 cm(-1); 3, J = 
      0.85 cm(-1)). The catalytic activity of the whole set of complexes has been
      tested with regard to the epoxidation of aromatic alkenes with peracetic acid. In
      the particular case of styrene, good selectivities and moderate
      enantioselectivities were obtained. Furthermore, total retention of the initial
      cis configuration was achieved when epoxidizing cis-beta-methylstyrene with the
      chloride complexes. In general, the epoxidation activity of these manganese
      complexes is strongly dependent on the steric encumbrance of the substrates
      employed.

PMID- 19771379
TI  - Depression as a determinant of quality of life in patients with chronic disease:
      data from Brazil.
AB  - BACKGROUND: Depressive symptoms are associated with impaired quality of life
      (QOL). However, there are scarce data comparing the magnitude of depression on
      QOL among persons with different chronic diseases in developing countries. This
      study aimed to evaluate the impact of depression on QOL in patients with ischemic
      heart disease (IHD) and end-stage renal disease (ESRD) in hemodialysis. METHODS:
      Cross-sectional survey conducted in 173 patients: 103 with IHD and 70 in
      hemodialysis. Depression was diagnosed by the Mini International Neuropsychiatric
      Interview-5.0 and depressive symptoms measured by Beck Depression Inventory. QOL
      was assessed through the Short-Form-36 (SF-36) and World Health Organization
      Quality of Life Instrument-brief (WHOQOL-brief). Multivariate analyses were
      performed to assess the association between variables and QOL. RESULTS:
      Depression prevalence was 14.3% among IHD patients and 9.9% in the hemodialysis
      group, and depressive symptoms were present in 39 and 36%, respectively.
      Regardless of the chronic condition, depressed patients presented lower QOL
      scores than non-depressed ones in all domains, and the most affected were role
      emotional, mental health and social functioning of SF-36, and psychological
      domain of WHOQOL-brief. In linear regression analysis, depressive symptoms were
      predictive for lower QOL in all domains, with the highest standardized beta
      coefficients (ranging from -0.26 to -0.64). CONCLUSION: Depression is an
      independent factor associated with worse QOL in IHD and ESRD patients. Among the
      priorities aiming at improving QOL must be evaluation and management of
      depressive symptoms.

PMID- 19771381
TI  - Organic-solvent-free extraction method for determination of carbamate and
      carbamoyloxime pesticides in soil and sediment samples.
AB  - This study evaluated the usefulness of monochloroacetic acid buffer (MCAAB) for
      extracting several carbamate/carbamoyloxime pesticides from a silt-loam soil and
      sediment, and an organic clay soil. The MCAAB extraction method, relative to
      acetonitrile and methanol extractants, was more accurate and precise for
      extraction of aldicarb, aldicarb sulfoxide, aldicarb sulfone, oxamyl, methomyl,
      carbofuran, 3-hydroxy-carbofuran, and propoxur; with recoveries ranging from
      78.8% to 121.1%. Recoveries of carbaryl and methiocarb ranged from 0% to 64.1%.
      The MCCAB extraction method did not perform well for extraction of most compounds
      from the organic clay soil, with recoveries ranging from 0% to 66.7%.

PMID- 19771380
TI  - Air-borne heavy metal contamination to dietary vegetables: a case study from
      India.
AB  - Contamination of edible parts of three dietary vegetables, Spinach (Spinacia
      oleracea L.), Radish (Raphanus sativus L.), and Tomato (Lycopersicon esculentum
      Mill.) by air-borne cadmium (Cd), chromium (Cr), copper (Cu), nickel (Ni), and
      lead (Pb) was determined using pot culture experiments at three sites in the city
      of Varanasi, India. The data revealed that although Cr and Cu in vegetables
      remained below their safe limits, about 68% of the total samples contained Cd,
      Ni, and Pb above their respective safe limits of 1.5, 1.5, and 2.5 MUg g(-1).
      Site wise synchrony and air accumulation factor (AAF) indicated that atmospheric
      deposition was the main contributor of metal contamination to vegetables. The
      study suggests that if the present trends of atmospheric deposition are
      continued, air-borne heavy metals will contaminate the agricultural produce with
      long-term health implications.

PMID- 19771382
TI  - Human health risk assessment of environmental exposure to organochlorine
      compounds in the Catalan stretch of the Ebro River, Spain.
AB  - In this study, the environmental impact and human health risks associated with
      exposure to organochlorine compounds (OCs) through soils and tap water in the
      Catalan stretch of the Ebro River, Spain, were investigated. The concentrations
      of polychlorinated biphenyls, hexachlorocyclohexanes, as well as DDT and
      derivates, were determined. Relatively low levels of these pollutants were
      observed, with mean concentrations ranging between 0.51-315.8 lg/kg and 0.05-74.6
      ng/L in soil and tap water, respectively. These values are similar to those found
      in a number of recent surveys over the world. In spite of the presence of a chlor
      alkali plant located upstream the Ebro River, which could mean a potential source
      of pollution, the current levels of OCs should not mean significant additional
      health risks for the local population.

PMID- 19771383
TI  - Probabilistic ecological risk assessment and source apportionment of polycyclic
      aromatic hydrocarbons in surface sediments from Yellow Sea.
AB  - Based on the concentrations of polycyclic aromatic hydrocarbons (PAHs) in 12
      surface sediment samples from Yellow sea, the relative risk of 9 PAHs was
      investigated using joint risk probability distribution curves and overlapping
      area, which were generated based on the distributions of exposure and acute
      toxicity data (LC(50)), and the sources of PAHs were apportioned using principal
      component analysis. It was found that joint probability curve and overlapping
      area indicated the acceptable ecological risk of individual PAHs, only a small
      fraction of the benthic organisms was affected. Among the nine PAHs studied, the
      overall risk of pyrene was the highest, with that of naphthalene the lowest. For
      lower exposure levels at which the percentage of species affected was less than
      10%, the risk associated with phenanthrene and fluorene were clearly higher than
      that of the other seven PAHs. It was indicated that PAHs in surface sediments
      mainly originated from vehicular emissions, coal combustion sources, coke oven
      emission and wood combustion, petroleum origin made little influence on sources
      of PAHs by PCA.

PMID- 19771385
TI  - Does visceral peritoneal closure affect post-cesarean urinary symptoms? A
      randomized clinical trial.
AB  - INTRODUCTION AND HYPOTHESIS: We hypothesized that upward bladder traction by
      visceral peritoneal closure during cesarean sections may have an impact on
      postpartum urinary complaints. METHODS: Based on a 90% power of the study and a
      95% confidence interval, a sample size of 114 patients in each arm was needed to
      detect a 15% difference between both groups regarding postpartum urinary
      incontinence. To account for follow-up losses, we prospectively randomized 620
      term primigravidas undergoing non-emergency cesareans into two groups (310 each):
      group 1, visceral peritoneal closure; group 2, non-closure. We compared perineal
      ultrasound findings 30 min before and 48 h after surgery. The UDI-6 questionnaire
      was used to assess urinary complaints. RESULTS: Group 1 showed significant
      widening of the posterior urethrovesical angle and alpha angle, more urethral
      descent 48 h postpartum and higher incidence of frequency, urge and stress
      incontinence 8 weeks postpartum. Symptoms disappeared almost completely after 6
      months. CONCLUSIONS: Compared to visceral peritoneal non-closure, cesarean with
      visceral closure is associated with significant postpartum frequency of urination
      and/or incontinence that disappear without treatment almost completely within 6
      months.

PMID- 19771386
TI  - New frontiers in pelvic floor surgery: avoiding   and managing the iatrogenically
      induced foreshortened,   constricted, or painful vagina.

PMID- 19771387
TI  - Insulin-like growth factor binding protein: a possible marker for the metabolic
      syndrome?
AB  - Insulin-like growth factor (IGF) binding proteins (IGFBPs) moved on to contain
      both IGF high- and low-affinity binders, exerting mitogenic and metabolic actions
      through its complex interplay between IGF/insulin and its IGF/insulin-independent
      manner. Progress on the metabolic-related function of IGFBPs has been rapid in
      recent years. A wealth of studies in 3T3-L1 adipocytes and the transgenic mice
      models demonstrated that IGFBPs played important roles in the pathogenesis of
      obesity and insulin resistance. Studies conducted in humans demonstrated the
      close relation between IGFBPs and the components of the metabolic syndrome.
      Abnormal expression of IGFBP was detected in various states of the metabolic
      disorders, suggesting that it could be used as a convenient and sensitive marker
      of insulin resistance, identification of insulin-resistant individuals at high
      cardiovascular risk, and may be an earlier marker of the metabolic syndrome.
      These exciting findings bring us new insight into the elucidation of the
      metabolic syndrome, which may have important clinical implications.

PMID- 19771388
TI  - Treatment of primary headache in children: a multicenter hospital-based study in
      France.
AB  - The aim of this 6-month, prospective, multicenter study of 398 children and
      adolescents with primary headaches was to collect data on headache treatment in
      neuropediatric departments. Treatments were compared before and after
      consultation. Prior to consultation, the acute treatments that had been
      prescribed most frequently were paracetamol (82.2% of children) and non-steroidal
      anti-inflammatory drugs treatment (53.5%); 10.3% had received a prophylactic
      treatment. No differences in either acute or prophylactic treatment with respect
      to headache diagnosis were observed. After the neuropediatric consultation,
      paracetamol was replaced by a non-steroidal anti-inflammatory drug in about three
      quarters of cases and by triptan in about one-quarter of cases. The number of
      children prescribed a prophylactic treatment nearly doubled, whereas there was a
      5-fold and 23-fold increase in psychotherapy and relaxation training,
      respectively, between pre-referral and referral. We conclude that specific
      treatments were underused for primary headache.

PMID- 19771389
TI  - A novel biomarker for retinal degeneration: vitreous body neurofilament proteins.
AB  - Retinal degeneration leads to release of cell-type specific proteins into the
      adjacent compartment. Here we investigated whether the neurofilament heavy chain
      protein (NfH) could be measured from the vitreous body and anterior chamber
      fluid. This prospective study included 85 patients who underwent vitrectomy (44
      retinal detachment, 12 macular hole, 15 epiretinal gliosis, 8 organ donors) or
      trabelectomy (six glaucoma). The cut-off level was calculated from the organ
      donors. An established enzyme-linked immunosorbent assay (ELISA, SMI35) was used
      for quantification of NfH (190-210 kDa). Measurable levels of NfH were detected
      from the vitreous body homogenate, but not from the anterior chamber fluid. The
      cut-off level was 0.29 ng/mL. A significant proportion of patients suffering from
      retinal detachment (43.2%, mean 0.74 ng/mL) had vitreous body NfH levels above
      cut-off when compared to organ donors (0%, 0.12 ng/mL, p = 0.02), epiretinal
      sclerosis (1.6%, 0.05 ng/mL, p = 0.01), macular hole (0%, 0.04 ng/mL, p = 0.004).
      Following retinal detachment, vitreous NfH-SMI35 levels correlated with time from
      onset (R = -0.3, p < 0.05), persisting for up to 2 years. This study shows that
      NfH can be quantified from the human vitreous body and may be a useful novel
      biomarker for retinal degeneration. The method can be applied for investigating
      the dynamics of retinal degeneration and the response to neuroprotective
      strategies in a broad range of retinal diseases in either clinical or
      experimental research.

PMID- 19771390
TI  - Expression of catechol-O-methyltransferase in the brain and periphery of normal
      and MPTP-treated common marmosets.
AB  - Catechol-O-methyltransferase (COMT) inhibition is widely used to potentiate the
      effects of levodopa in Parkinson's disease but the effects of nigral dopaminergic
      cell loss and levodopa treatment on COMT activity are not known. The present
      study investigated the expression of COMT in the brain and liver of normal common
      marmosets, and animals treated with MPTP and those treated with levodopa to
      induce dyskinesia. Reverse transcript PCR demonstrated the expression of COMT
      mRNA in the liver, cortex and striatum of normal marmosets. Using Western
      blotting, the presence of two subunits of COMT protein, membrane bound COMT (MB
      COMT) and soluble COMT (S-COMT), was shown in the liver, cortex and striatum of
      normal marmosets. Quantitative analysis of the MB-COMT and S-COMT subunit bands
      showed that there was no significant difference in the density of bands in MPTP
      treated marmosets or those exposed to levodopa compared to normal animals. COMT
      immunoreactivity was expressed in many brain regions including the cortex and
      striatum. No difference in COMT staining intensity was observed between normal,
      MPTP exposed or MPTP plus levodopa treated animals. COMT immunostaining was
      present in most striatal neurones and it was occasionally seen in glial cells.
      The data from present study demonstrated the expression of COMT mRNA and protein
      in the brain of common marmoset contrary to a previous report that it is not
      expressed in this species. COMT activity appears unaffected by loss of the
      dopaminergic nigro-striatal pathway and levodopa treatment.

PMID- 19771391
TI  - Upper gastrointestinal findings in Huntington's disease: patients suffer but do
      not complain.
AB  - We investigated, retrospectively, the prevalence of gastroesophageal inflammation
      in patients with Huntington's disease (HD) during 10 years in our center. We
      found a high prevalence of gastritis or esophagitis even in patients without
      complaints, indicating that gastrointestinal disease is more common in HD than
      patients' complaints. There was no correlation with motor disturbances but with
      the duration and severity of HD. Influences from the disease itself as well as
      secondary mechanisms like malnutrition, medication and general disability may
      contribute.

PMID- 19771392
TI  - The effect of temperature on hospital admissions in nine California counties.
AB  - OBJECTIVES: This study examined the association between mean daily apparent
      temperature and hospital admissions for several diseases in nine California
      counties from May to September, 1999 to 2005. METHODS: We conducted a time
      stratified case-crossover study limited to cases with residential zip codes
      located within 10 km of a temperature monitor. County-specific estimates were
      combined, using a random effects meta-analysis. The analyses also considered the
      effects of ozone and particulate matter (PM(2.5)). RESULTS: We found that a 10
      degrees F increase in mean apparent temperature was associated with a 3.5% [95%
      confidence interval (CI) 1.5-5.6] increase in ischemic stroke and increases in
      several other disease-specific outcomes including all respiratory diseases (2.0%,
      95% CI 0.7-3.2), pneumonia (3.7%, 95% CI 1.7-3.7), dehydration (10.8%, 95% CI 8.3
      13.6), diabetes (3.1%, 95% CI 0.4-5.9), and acute renal failure (7.4%, 95% CI 4.0
      10.9). There was little evidence that the temperature effects we found were due
      to confounding by either PM(2.5) or ozone. CONCLUSION: Our results indicate that
      increases in ambient temperature have important public health impacts on
      morbidity.

PMID- 19771393
TI  - Role of men in promoting the uptake of HPV vaccinations: focus groups' finding
      from a developing country.
AB  - OBJECTIVES: Better outcomes of human papillomavirus (HPV) vaccination would be
      expected if men become full partners and advocates in vaccination initiative. Men
      involvement has important implication especially within the context that they are
      equally responsible for spreading the virus. METHODS: Twenty-seven men took part
      in four focus group discussions carried out to assess men's attitudes toward the
      HPV vaccine between October and November 2007. RESULTS: The results revealed that
      men have low awareness about the newly release vaccine and minimal knowledge of
      HPV and its association with cervical cancer. When provided with information,
      most men were in favor of protecting their spouses, partners, or daughters from
      cervical cancer using the vaccine. They were aware of the effects of men's risk
      behavioral patterns on women's risk for acquiring HPV infections. Many needed
      assurance about the vaccine's long-term safety and efficacy. They also expressed
      concern over the high cost of the vaccine. Men in this study played an
      influential role in the vaccination decision of their child and sexual partners.
      Many were in favor of male vaccination for cervical cancer prevention of their
      spouse or partner. CONCLUSIONS: Vaccine advocacy should put special emphasis on
      men as sexual partners, husbands, and fathers from a gender equality and
      partnership perspective. The findings are useful in facilitating the development
      of strategies for effective immunization initiatives.

PMID- 19771394
TI  - NBBS isolated from Pygeum africanum bark exhibits androgen antagonistic activity,
      inhibits AR nuclear translocation and prostate cancer cell growth.
AB  - Extracts from Pygeum africanum are used in the treatment of prostatitis, benign
      prostatic hyperplasia (BPH) and prostate cancer (PCa). The ligand-activated human
      androgen receptor (AR) is known to control the growth of the prostate gland.
      Inhibition of human AR is therefore a major goal in treatment of patients. Here,
      we characterize the compound N-butylbenzene-sulfonamide (NBBS) isolated from P.
      africanum as a specific AR antagonist. This antihormonal activity inhibits AR-
      and progesterone receptor- (PR) mediated transactivation, but not the related
      human glucocorticoid receptor (GR) or the estrogen receptors (ERalpha or ERbeta).
      Importantly, NBBS inhibits both endogenous PSA expression and growth of human PCa
      cells. Mechanistically, NBBS binds to AR and inhibits its translocation to the
      cell nucleus. Furthermore, using a battery of chemically synthesized derivatives
      of NBBS we revealed important structural aspects for androgen antagonism and have
      identified more potent AR antagonistic compounds. Our data suggest that NBBS is
      one of the active compounds of P. africanum bark and may serve as a naturally
      occurring, novel therapeutic agent for treatment of prostatic diseases. Thus,
      NBBS and its derivatives may serve as novel chemical platform for treatment
      prostatitis, BPH and PCa.

PMID- 19771396
TI  - An insight into some relevant aspects concerning eriophyoid mites inhabiting
      forests, ornamental trees and shrubs.
AB  - Worldwide a great variety of eriophyoid mites inhabit forest canopy trees and
      ornamental plants that are used in city parks, squares and boulevards. An
      analysis of the relevant bibliography portrays only a fragmentary knowledge and
      the majority of our information concerns the temperate zone. Three case studies
      are presented as examples of different approaches to solve problems connected
      with eriophyoid mites of forest and ornamental trees. The first example deals
      with eriophyoids of a temperate zone forest in a natural environment, focusing on
      conifers which represent the largest component. The second case study documents a
      possible approach to obtain greater knowledge and control of the bud mite
      species, Trisetacus juniperinus (Nalepa) on Cupressaceae. This is a harmless
      species in the natural environment which becomes a serious pest in nurseries and
      young stands of Cupressus sempervirens in the Mediterranean region. The final
      case study reports on long-term studies carried out in Poland on injurious
      eriophyoid species that are found in nurseries, city greenery and parks. This
      paper also discusses future perspectives for research on eriophyoid mites living
      on forest and ornamental plants.

PMID- 19771395
TI  - The oncogenic roles of Notch1 in astrocytic gliomas in vitro and in vivo.
AB  - Notch receptors play an essential role in cellular processes during embryonic and
      postnatal development, including maintenance of stem cell self-renewal,
      proliferation, and determination of cell fate and apoptosis. Deregulation of
      Notch signaling has been implicated in some genetic diseases and tumorigenesis.
      The function of Notch signaling in a variety of tumors can be either oncogenic or
      tumor-suppressive, depending on the cellular context. In this study, Notch1
      overexpression was observed in the majority of 45 astrocytic gliomas with
      different grades and in U251MG glioma cells. Transfection of siRNA targeting
      Notch1 into U251 cells in vitro downregulated Notch1 expression, associated with
      inhibition of cell growth, arrest of cell cycle, reduction of cell invasiveness,
      and induction of cell apoptosis. Meanwhile, tumor growth was delayed in
      established subcutaneous gliomas in nude mice treated with Notch1 siRNA in vivo.
      These results suggest that Notch1 plays an important oncogenic role in the
      development and progression of astrocytic gliomas. Furthermore, knockdown of
      Notch1 expression by siRNA simultaneously downregulated the expression of EGFR
      and the important components of its downstream pathways, including PI3K, p-AKT, K
      Ras, cyclin D1 and MMP9, indicating the crosstalk and interaction of Notch and
      EGFR signaling pathways.

PMID- 19771397
TI  - Recommended procedures and techniques for morphological studies of Eriophyoidea
      (Acari: Prostigmata).
AB  - Methods used for sample storage, specimen clearing, slide mounting, species
      illustration and morphometric description in alpha-taxonomic studies are
      essential for the Eriophyoidea. Eriophyoid mites are very tiny and delicate, for
      which truly permanent specimen slides currently cannot be prepared, resulting in
      eventual loss of material, including type specimens. Often, published
      descriptions and drawings have not achieved the required level of quality, and
      thus many relevant taxonomic details have been permanently lost or neglected.
      These shortcomings can make certain identifications impossible and cause
      significant confusion. Consequently, there is a considerable need for accurate
      and uniform descriptive and illustrative data for the Eriophyoidea. Based on
      their expertise on this topic, the authors provide guidelines and advices,
      assisted also by illustrations, of the main critical aspects in managing
      eriophyoid mites in order to supplement and improve techniques for handling and
      preparation of specimens, and for improving their taxonomic study. The effects of
      the short- and long-term preservation methods (i.e., fresh, dried and liquid
      preservative choices) on digesting the internal tissues of the mites are
      discussed. Clearing and mounting procedures are analyzed, and special tips are
      suggested for handling mites and designing tools needed during these steps.
      Methods for recovering specimens from unsuitable slides (i.e., undercleared and
      overcleared specimens) are proposed and described. Techniques and tricks to
      produce descriptive line drawings of good quality are highlighted, and the
      content to include in plates is stressed. Finally, detailed instructions for
      standardization of measurements are given.

PMID- 19771398
TI  - Development of acaricide resistance in Pacific spider mite (Tetranychus
      pacificus) from California vineyards.
AB  - In recent years, grape growers in California reported failures of acaricides
      against Tetranychus pacificus McGregor. We collected T. pacificus populations
      from four vineyards and tested them for resistance to bifenazate, propargite and
      pyridaben. In addition, we sequenced part of the cytochrome b gene of bifenazate
      resistant and -susceptible T. pacificus to test for the presence of mutations
      reported to confer resistance to the congeneric T. urticae. None of the mutations
      conferring resistance to bifenazate in T. urticae were present in resistant T.
      pacificus. Resistance levels ranged from full susceptibility to statistically
      significant 11-fold resistance to pyridaben, sevenfold resistance to bifenazate
      and fourfold resistance to propargite compared to a susceptible population.
      Despite the relatively low levels of resistance detected, we estimated that under
      the conditions of our study the highest field rates of bifenazate and pyridaben
      application would cause less than 58 and 66% mortality of adult females in the
      most resistant populations, respectively. In contrast, field rates of propargite
      application would cause close to 100% mortality in the least susceptible
      population. These results highlight a potential link between resistance
      development and reduced field effectiveness for bifenazate and pyridaben.
      Finally, T. pacificus may be more tolerant to bifenazate and propargite than T.
      urticae, since the LC(50) values for the susceptible population of T. pacificus
      were several times higher than LC(50)'s reported for susceptible T. urticae.

PMID- 19771399
TI  - MHC class II regulation by epigenetic agents and microRNAs.
AB  - MicroRNAs have been shown to regulate gene expression both transcriptionally and
      translationally. Here, we examine evidence that various stresses regulate miRNAs
      which, in turn, regulate immune gene levels. Multiple studies are reviewed
      showing altered microRNA levels in normal cells under stress and in various
      disease states, including cancer. Unexpected was the finding that Dicer
      expression is altered by treatments with several agents, such as interferons and
      cortisone, employed in the treatment of immune disorders. Potential signal
      transduction pathways, including JAK/Stat, PI3K and PKR, that may regulate Dicer
      and microRNA levels in normal and stressed mammalian cells are discussed.

PMID- 19771400
TI  - Generation of tolerogenic dendritic cells via the E-cadherin/beta-catenin
      signaling pathway.
AB  - Besides their well-characterized role as the initiator of adaptive immune
      responses, dendritic cells (DCs) play a critical role in the induction and
      maintenance of self-tolerance, the failure of which could lead to
      autoimmune/inflammatory diseases. Although it is clear that tolerance is a
      property of DCs at the steady state, the molecular mechanisms governing their
      generation, function and regulation remain elusive. Our recent studies have
      uncovered the E-cadherin/beta-catenin-signaling pathway as a novel maturation
      pathway that achieves DC maturation without inflammatory cytokines. As a result,
      E-cadherin-stimulated DCs elicited an entirely different T cell response in vivo,
      generating T cells with a regulatory as opposed to an effector phenotype. These
      DCs induced tolerance in vivo and more importantly, immunization with these DCs
      provided complete protection against autoimmune diseases in experimental
      autoimmune encephalomyelitis (EAE). Interestingly, while DCs matured upon
      disruption of E-cadherin-mediated clusters were functional tolerogenic, upon
      further TLR ligation, they displayed a strong Th1 cytokine profile and much
      enhanced antigen presentation capacity consistent with enhanced immunity. Thus, E
      cadherin/beta-catenin-signaling might serve as a novel signal that contributes to
      the elusive steady-state "tolerogenic DCs". Targeting E-cadherin/beta-catenin
      signaling to either enhance or reduce DC-mediated tolerance might represent an
      attractive new strategy to achieve antigen-specific immunotherapy for cancers and
      autoimmune/inflammatory diseases.

PMID- 19771401
TI  - Production of acetone-butanol-ethanol (ABE) in direct fermentation of cassava by
      Clostridium saccharoperbutylacetonicum N1-4.
AB  - In this work, acetone-butanol-ethanol (ABE) fermentation characteristics of
      cassava starch and cassava chips when using Clostridium
      saccharoperbutylacetonicum N1-4 was presented. The obtained results in batch mode
      using a 1-L fermenter showed that C. saccharoperbutylacetonicum N1-4 was a
      hyperamylolytic strain and capable of producing solvents efficiently from cassava
      starch and cassava chips, which was comparable to when glucose was used. Batch
      fermentation of cassava starch and cassava chips resulted in 21.0 and 19.4 g/L of
      total solvent as compared with 24.2 g/L of total solvent when using glucose.
      Solvent productivity in fermentation of cassava starch was from 42% to 63% higher
      than that obtained in fermentation using corn and sago starches in the same
      condition. In fermentation of cassava starch and cassava chips, maximum butanol
      concentration was 16.9 and 15.5 g/L, respectively. Solvent yield and butanol
      yield (based on potential glucose) was 0.33 and 0.41, respectively, for
      fermentation of cassava starch and 0.30 and 0.38, respectively for fermentation
      using cassava chips.

PMID- 19771402
TI  - [Vaccine safety].
AB  - Vaccinations rank among the most effective preventive measures for protection
      against infectious diseases. Advances in development, production, and control of
      vaccines facilitate the increasing standards of vaccine safety and tolerance.
      Comprehensive pre-clinical and clinical tests as well as modern manufacturing and
      testing methods ensure that vaccines marketed nowadays are safe. As a rule,
      clinical trials performed before granting the marketing authorisation identify
      the most frequent adverse events and these results are used to evaluate the
      safety of the product. Such trials can identify relatively rare adverse events,
      which occur with a frequency of 1:1,000 to 1:10,000 of all vaccinated
      individuals. These adverse events will then be included in the summary of product
      characteristics (SPC) for the vaccine. Even after comprehensive clinical trials
      of vaccines, it is possible that very rare adverse events may be observed for the
      first time during general use of a vaccine. In recent years concern over real and
      alleged risks of vaccines relative to their benefit has grown in many countries
      including Germany. One reason for this is the fact that most infections that were
      previously feared have now faded from memory. This situation can be ascribed in
      part to the success of vaccination. In recent years an increased awareness of
      substantiated and assumed risks following immunization has been reported in
      Germany as well as many other countries. In part this may be due to the absence
      of infectious disease-related mortality and morbidity and to the fact that the
      severity of vaccine-preventable diseases is no longer observable. Consequently,
      rare and hypothetical adverse events attain undue public attention. As
      vaccination willingness diminishes, a resulting lower vaccination rate renders
      the population susceptible to the natural wild type infection with concomitant
      increases in mortality and morbidity of vaccine-preventable diseases. Thus, very
      rare or even unproven adverse events have attracted public attention. Declining
      vaccination rates resulting from these fears may result in a renewed increase of
      vaccine-preventable diseases. Adverse events following immunization (AEFI) need
      to be recognized and adequately assessed. This review presents the scientific
      knowledge concerning causality and frequency of several AEFI and hypothetical
      risks.

PMID- 19771403
TI  - [Does dilution have an impact on cosmetic results with BoNT/A? Complex-protein
      free BoNT/A for treatment of glabella lines].
AB  - BACKGROUND: In this 2-armed, randomized study we investigated the efficacy and
      tolerability of complex-protein-free botulinum neurotoxin type A (BoNT/A),
      applied in two different dilution volumes for treatment of glabellar lines.
      PATIENTS AND METHODS: 40 patients with grade 2-3 glabellar lines (Facial Wrinkle
      Scale) received treatment with 25U BoNT/A (Xeomin). 100U of botulinum neurotoxin
      were diluted in 2.5 ml (group I) or 4 ml sodium chloride solution (group II).
      Responders showed an improvement in the wrinkle score (independent rater) of at
      least one point. RESULTS. Response rates two weeks after treatment were 100% /
      89.5%, at 3 months 84.2% / 64.7% and at 4 months 53.3% / 61.5% (groups I / II
      respectively). There was no significant difference between the two dilutions.
      CONCLUSION: Complex-protein-free botulinum neurotoxin type A in both dilutions
      effectively reduced severity of glabellar lines. There was no statistically
      significant difference in efficacy between the two dilutions.

PMID- 19771404
TI  - [Inside-Out. Probiotics and atopic dermatitis].
AB  - Orally administered probiotics have been employed for the prevention and therapy
      of atopic dermatitis in recent years, because both theoretical considerations and
      animal models suggested positive effects were likely. Current clinical studies
      make it clear that oral probiotics are not indicated for the therapy of mild,
      moderate or severe atopic dermatitis. A prevention study from Finland described a
      marked positive effect of lactobacilli on the rate of atopic dermatitis when the
      bacteria were given orally to the pregnant mother and the newborn. However, these
      positive results could not be reproduced by other investigators. Until these
      varying results are explained, no recommendation can be made for use of oral
      probiotics to prevent atopic dermatitis, as is stated in the current German S3
      guideline on the prevention of allergies.

PMID- 19771405
TI  - [Sorafenib in advanced hepatocellular carcinoma].

PMID- 19771406
TI  - [19-year-old kick-boxer with hematemesis and splenomegaly].
AB  - Traumatic portal vein thrombosis is a rare cause of nonmalignant, noncirrhotic
      portal hypertension. We report a case of a 19-year old patient, who presented
      with variceal bleeding and splenomegaly. Diagnosis was based on the history of
      kickboxing and an otherwise negative etiological investigation. The patient
      underwent endoscopic therapy and portosystemic shunt operation (Warren-shunt) due
      to cavernous transformation and severe hypersplenism. Thereafter the patient
      remained asymptomatic.

PMID- 19771407
TI  - Near-fatal acute postobstructive pulmonary oedema requiring extracorporal
      membrane oxygenation.

PMID- 19771408
TI  - Diagnostic considerations regarding  pediatric delirium: a review and a proposal 
      for an algorithm for pediatric intensive care  units.
AB  - CONTEXT: If delirium is not diagnosed, it is unlikely that any effort will be
      made to reverse it. Given evidence for under-diagnosis, tools that aid
      recognition are required. OBJECTIVE: Relating three presentations of pediatric
      delirium (PD) to standard criteria and developing a diagnostic algorithm.
      RESULTS: Delirium-inducing factors, disturbance of consciousness and inattention
      are common in PICU patients: a pre-delirious state is present in most. An
      algorithm is introduced, containing (1) evaluation of the sedation-agitation
      level, (2) psychometric assessment of behavior and (3) opinion of the caregivers.
      DISCUSSION: It may be argued that the behavioral focus of the algorithm would
      benefit from the inclusion of neurocognitive measures. LIMITATIONS: No
      sufficiently validated diagnostic instrument covering the entire algorithm is
      available yet. CONCLUSION: This is the first proposal for a PD diagnostic
      algorithm. Given the high prevalence of predelirious states at the PICU, daily
      evaluation is mandatory. Future algorithmic refinement is urgently required.

PMID- 19771409
TI  - Is volume and leak monitoring feasible during  nasopharyngeal continuous positive
      airway  pressure in neonates?
AB  - OBJECTIVE: To investigate tidal volume (VT) and leak measurements during
      continuous positive airway pressure (CPAP) in neonates using a commercial
      ventilatory device equipped with a flow sensor at the Y-piece. DESIGN: Randomized
      cross-over trial. SETTING: Neonatal intensive care unit level III. PATIENTS:
      Thirty-two infants, median (range) birth weight 1,435 (710-2,730) g, gestational
      age 30 (24-38) weeks. INTERVENTIONS: During nasopharyngeal CPAP, leak and VT were
      measured with and without occlusion of the contralateral nostril using the Leoni
      ventilator (Heinen & Lowenstein, Germany) and a recently developed algorithm to
      correct measured VT in the presence of leaks. The measuring range of the Leoni is
      limited to leaks <90%. MAIN RESULTS: Analyzable measurements with leaks <90%
      could be obtained in 12.5% of the patients with open nostril, and in 65.6% with
      occluded nostril. Calculated leak flow after nostril occlusion was 23 (3-77) ml
      min(-1) with closed mouth. Leak flow increased significantly if mouth was opened
      (548 (0-1,394) ml min(-1), p<0.001), but was probably even higher where leaks
      exceeded 90%. Mean expiratory volume +/- SD was 5.8 +/- 1.3 ml kg(-1) (corrected
      VT 5.9 +/-1.2 ml kg(-1)) for leaks <20%, and 3.7 +/-1.4 ml kg(-1) (corrected VT
      5.8 +/- 2.2 ml kg(-1)) for leaks between 20 and 69%. CONCLUSIONS: Leak and
      corrected VT could be determined in the presence of leaks of up to 69%, but leaks
      during CPAP often exceeded the measuring range. Reliable volume and leak
      monitoring was not possible with the tested equipment during nasopharyngeal CPAP.
      Advanced equipment is necessary to further investigate the effects of leaks on
      neonatal CPAP therapy.

PMID- 19771410
TI  - Fellows' in intensive care medicine views on professionalism and how they learn
      it.
AB  - INTRODUCTION: The emphasis on the importance of professionalism in a recent
      CoBaTrICE-IT paper was impressive. However, insight into the elements of
      professionalism as perceived relevant for intensivists from the fellows' view,
      and how these are taught and learned, is limited. OBJECTIVES AND METHODS: A
      nationwide study was performed in 2007-2008. All ICM fellows (n = 90) were sent a
      questionnaire containing the following questions regarding training in
      professionalism (7-point Likert scale (1 = very inadequate, 7 = very adequate)):
      which are the elements perceived to be important in intensivists'' daily practice
      (38 items, cat. I)? Which methods of learning and teaching are recognised (16
      items, cat. II)? Which methods of teaching and learning are considered especially
      useful (16 items, cat. III)? Finally, the perceived quantity and quality of
      formal and informal learning methods, as well as the responsible organisational
      body was studied. Data were analysed using SPSS 15.0. RESULTS: Response was 75.5
      % (n = 68), mean age 34 years. Regarding Elements, scores on virtually all items
      were high. The factor 'striving for excellence' explained half the variance. Two
      other aspects, 'Teamwork' and 'Dealing with ethical dilemmas', were identified.
      Regarding Methods, three dimensions, 'formal curriculum'', 'private and academic
      experiences' and 'role modelling', proved important. The factor 'formal
      curriculum' explained most of the variance. Regarding Usefulness the same
      factors, now mainly explained by the factor Private and academic experiences,
      emerged with variance. In both categories the items 'observations in daily
      practice' and 'watching television programmes like ER and House' were the highest
      and lowest-scoring items (5.99 and 5.81, and 2.69 and 2.49, respectively). Mean
      scores regarding the quantity of formal and informal teaching were 4.06 and 4.58
      (range 1.841 and 1.519). For the quality of teaching, the figures were 4.22 and
      4.52 (range 1.659 and 1.560, respectively). 54 suggestions for improvement of
      teaching were documented. The need for some form of formal teaching of
      professionalism aspects as well as for feedback was most frequently mentioned (n
      = 19 and 16). The local training centres are considered and should remain pivotal
      for teaching professionalism issues (n = 17 and 28). CONCLUSIONS: Almost all
      elements of professionalism were considered relevant to intensivists' daily
      practice. Although formal teaching methods regarding professionalism aspects are
      easily recognised in daily practice, learning by personal experiences and
      informal ways quantitatively plays a more important, and more valued role.
      Qualitative comments, nevertheless, stress the need for providing and receiving
      (solicited and unsolicited) feedback, thereby requesting expansion of formal
      teaching methods. The local training centres (should continue to) play a major
      role in teaching professionalism, although an additional role for the
      (inter)national intensive care organisations remains.

PMID- 19771411
TI  - Characterization of the mineral phosphate solubilizing activity of Serratia
      marcescens CTM 50650 isolated from the phosphate mine of Gafsa.
AB  - The mineral phosphate solubilizing (MPS) ability of a Serratia marcescens strain,
      namely CTM 50650, isolated from the phosphate mine of Gafsa, was characterized on
      a chemically defined medium (NBRIP broth). Various insoluble inorganic
      phosphates, including rock phosphate (RP), calcium phosphate (CaHPO(4)), tri
      calcium phosphate (Ca(3)(PO(4))(2)) and hydroxyapatite were tested as sole
      sources of phosphate for bacterial growth. Solubilization of these phosphates by
      S. marcescens CTM 50650 was very efficient. Indeed, under optimal conditions, the
      soluble phosphorus (P) concentration it produced reached 967, 500, 595 and 326
      mg/l from CaHPO(4), Ca(3)(PO(4))(2), hydroxyapatite and RP, respectively. Study
      of the mechanisms involved in the MPS activity of CTM 50650, showed that
      phosphate solubilization was concomitant with significant drop in pH. HPLC
      analysis of culture supernatants revealed the secretion of gluconic acid (GA)
      resulting from direct oxidation pathway of glucose when the CTM 50650 cells were
      grown on NBRIP containing glucose as unique carbon source. This was correlated
      with the simultaneous detection by PCR for the first time in a S. marcescens
      strain producing GA, of a gene encoding glucose dehydrogenase responsible for GA
      production, as well as the genes pqqA, B, C and E involved in biosynthesis of its
      PQQ cofactor. This study is expected to lead to the development of an
      environmental-friendly process for fertilizer production considering the capacity
      of S. marcescens CTM 50650 to achieve yields of P extraction up to 75% from the
      Gafsa RP.

PMID- 19771412
TI  - A new beta-galactosidase with a low temperature optimum isolated from the
      Antarctic Arthrobacter sp. 20B: gene cloning, purification and characterization.
AB  - A psychrotrophic bacterium producing a cold-adapted beta-galactosidase upon
      growth at low temperatures was classified as Arthrobacter sp. 20B. A genomic DNA
      library of strain 20B introduced into Escherichia coli TOP10F' and screening on X
      Gal (5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside)-containing agar plates
      led to the isolation of beta-galactosidase gene. The beta-galactosidase gene
      (bgaS) encoding a protein of 1,053 amino acids, with a calculated molecular mass
      of 113,695 kDa. Analysis of the amino acid sequence of BgaS protein, deduced from
      the bgaS ORF, suggested that it is a member of the glycosyl hydrolase family 2. A
      native cold-adapted beta-galactosidase was purified to homogeneity and
      characterized. It is a homotetrameric enzyme, each subunit being approximately
      116 kDa polypeptide as deduced from native and SDS-PAGE, respectively. The beta
      galactosidase was optimally active at pH 6.0-8.0 and 25 degrees Celsius. P
      nitrophenyl-beta-D-galactopyranoside (PNPG) is its preferred substrate (three
      times higher activity than for ONPG-o-nitrophenyl-beta-D-galactopyranoside). The
      Arthrobacter sp. 20B beta-galactosidase is activated by thiol compounds (53% rise
      in activity in the presence of 10 mM 2-mercaptoethanol), some metal ions
      (activity increased by 50% for Na(+), K(+) and by 11% for Mn(2+)) and inactivated
      by pCMB (4-chloro-mercuribenzoic acid) and heavy metal ions (Pb(2+), Zn(2+),
      Cu(2+)).

PMID- 19771413
TI  - NifH-based studies on azotobacterial diversity in cotton soils of India.
AB  - In order to promote the use of Azotobacter inoculants for cotton crop, a complete
      characterization of soil isolates of Azotobacter, isolated and screened on the
      basis of physiological properties, from four different cotton-wheat cropping
      regions of India was carried out, and their genetic diversity determined by RFLP
      (restriction fragment length polymorphism) analysis of the functional gene nifH.
      Genetic analysis of these isolates depicted a similarity coefficient of > or =
      80% among them, suggesting that though the isolates were obtained from different
      cotton soils of India, still they have large commonality in the nifH gene and
      constituted a homogeneous nifH population.

PMID- 19771414
TI  - Quantitative determination of TEGDMA, BHT, and DMABEE in eluates from polymerized
      resin-based dental restorative materials by use of GC/MS.
AB  - This study investigated the leaching of ingredients from several commercial
      dental composite resins cured with LED, and immersed in methanol or water for 24
      h, respectively. The composites used were: Admira Dentin (VOCO), Artemis Schmelz
      (Enamel) (Ivoclar Vivadent), Els extra low shrinkage (Saremco Dental), Filtek
      Supreme XT Dentin (3 M ESPE), Gradia Direct (GC), Venus & Venus flow (Heraeus
      Kulzer), and XRV Herculite Prodigy Enamel (Kerr). From each dental composite four
      specimens with defined structure and 100-mg net weight were made. After the
      polymerization process, according to manufacturer's instructions, the specimens
      were immersed in either 1 ml water or 1 ml methanol and incubated at 37 degrees C
      for 24 h. Eluted ingredients triethyleneglycoldimethacrylate (TEGDMA), 2,6-di
      tert-butyl-4-methylphenol (BHT), and 4-N,N-dimethylaminobenzoicacidethylester
      (DMABEE) were detected and quantified using gas chromatography-mass spectrometry
      (GC-MS). The amounts of the detected analytes from 100 mg polymerized composites
      ranged between the following values: TEGDMA: 0-0.5 mg (water), 0-1.6 mg
      (methanol); BHT: 0-0.03 MUg (water), 0-0.11 mg (methanol); and DMABEE: 0-0.11 mg
      (water), 0-1.4 mg (methanol). We conclude from the results that the elution rates
      into methanol and water differ significantly. Furthermore, it is concluded that
      all the determined amounts eluting from the composites are far below toxic
      relevant concentrations.

PMID- 19771415
TI  - Vacuum annealing phenomena in ultrathin TiDy/Pd bi-layer films evaporated on
      Si(100) as studied by TEM and XPS.
AB  - Using a combination of TEM and XPS, we made an analysis of the complex high
      temperature annealing effect on ultrathin titanium deuteride (TiD(y)) films
      evaporated on a Si(100) substrate and covered by an ultrathin palladium layer.
      Both the preparation and annealing of the TiD(y)/Pd bi-layer films were performed
      in situ under UHV conditions. It was found that the surface and bulk morphology
      of the bi-layer film as well as that of the Si substrate material undergo a
      microstructural and chemical conversion after annealing and annealing-induced
      deuterium evolution from the TiD(y) phase. Energy-filtered TEM (EFTEM) mapping of
      cross-section images and argon ion sputter depth profiling XPS analysis revealed
      both a broad intermixing between the Ti and Pd layers and an extensive inter
      diffusion of Si from the substrate into the film bulk area. Segregation of Ti at
      the Pd top layer surface was found to occur by means of angle-resolved XPS
      (ARXPS) and the EFTEM analyses. Selected area diffraction (SAD) and XPS provided
      evidence for the formation of a new PdTi(2) bimetallic phase within the top
      region of the annealed film. Moreover, these techniques allowed to detect the
      initial stages of TiSi phase formation within the film-substrate interlayer.

PMID- 19771416
TI  - Signal limitations in tip-enhanced Raman scattering: the challenge to become a
      routine analytical technique.
AB  - The fundamental parameters and limitations that determine the signal strength in
      tip-enhanced Raman scattering (TERS) are discussed. A semiquantitative analysis
      of the Raman signal expected in different experimental geometries and with
      different sample systems is presented, taking into account experimental
      parameters including Fresnel factor, numerical aperture of the illumination and
      collection optics, detection efficiency, and the Raman scattering cross section
      of the material. A top/side-on illumination geometry is essential for the study
      of nontransparent samples. It can yield the highest signal levels when strong tip
      sample coupling using a metallic substrate provides large field enhancement. In
      contrast, axial/through-sample illumination is limited to transparent sample
      materials. Although conceptually simpler in experimental implementation and
      despite high numerical aperture signal collection efficiency, signals are
      generally weaker due to limited field enhancement. Crystalline solids with small
      Raman cross sections and dense molecular/biological systems with unavoidable far
      field background provide the biggest challenge for TERS analysis yet at the same
      time hold the most exciting outstanding scientific questions TERS has the
      potential to answer.

PMID- 19771417
TI  - Reach-to-grasp movement as a minimization process.
AB  - It is known that hand transport and grasping are functionally different but
      spatially coordinated components of reach-to-grasp (RTG) movements. As an
      extension of this notion, we suggested that body segments involved in RTG
      movements are controlled as a coherent ensemble by a global minimization process
      associated with the necessity for the hand to reach the motor goal. Different RTG
      components emerge following this process without pre-programming. Specifically,
      the minimization process may result from the tendency of neuromuscular elements
      to diminish the spatial gap between the actual arm-hand configuration and its
      virtual (referent) configuration specified by the brain. The referent
      configuration is specified depending on the object shape, localization, and
      orientation. Since the minimization process is gradual, it can be interrupted and
      resumed following mechanical perturbations, at any phase during RTG movements,
      including hand closure. To test this prediction of the minimization hypothesis,
      we asked subjects to reach and grasp a cube placed within the reach of the arm.
      Vision was prevented during movement until the hand returned to its initial
      position. As predicted, by arresting wrist motion at different points of hand
      transport in randomly selected trials, it was possible to halt changes in hand
      aperture at any phase, not only during hand opening but also during hand closure.
      Aperture changes resumed soon after the wrist was released. Another test of the
      minimization hypothesis was made in RTG movements to an object placed beyond the
      reach of the arm. It has previously been shown (Rossi et al. in J Physiol 538:659
      671, 2002) that in such movements, the trunk motion begins to contribute to hand
      transport only after a critical phase when the shifts in the referent arm
      configuration have finished (at about the time when hand velocity is maximal).
      The minimization rule suggests that when the virtual contribution of the arm to
      hand transport is completed, guidance of hand aperture switches from the arm to
      the trunk control system. As a consequence, hand aperture changes can be halted
      by trunk arrests but only if they are prolonged beyond a critical phase. As
      predicted, hand transport and hand aperture in RTG movements beyond the reach of
      the arm were halted by trunk arrests only if they were prolonged beyond the time
      of peak hand velocity. Hand motion and aperture changes resumed only when the
      trunk was released. While supporting the minimization hypothesis, our findings
      imply that not only spatial but also temporal characteristics of each component,
      including the shortest, hand closure component of RTG movements, are controlled
      in a flexible, task-specific way.

PMID- 19771418
TI  - Stretch reflexes and joint dynamics in rheumatoid arthritis.
AB  - In clinically diagnosed rheumatoid arthritis (RA), studies were conducted to
      investigate the reflex and passive tissue contribution to measured increases in
      joint stiffness in the resting upper limb and during constant contractions of an
      attached muscle. The tonic stretch reflex was induced by a servo-controlled
      sinusoidal stretch perturbation of the metacarpophalangeal joint of RA patients,
      and age- and sex-matched controls. The resulting reflexes and mechanical changes
      in the RA affected joint were explored. Surface electromyographic (EMG)
      measurements were obtained from first dorsal interosseus muscle. Reflex gain
      (EMG/joint angle amplitude ratio), phase difference (reflex delay after stretch),
      coherence square (proportion of EMG variance accounted for by joint angle
      changes), joint mechanical gain (torque-joint angle amplitude ratio) and
      mechanical phase difference (torque response delay after stretch) were
      determined. RA patients showed decreased reflex gain that was partly due to
      coexistent severe muscle weakness, as determined from maximum voluntary
      contraction and grip pressure estimates. The decreased reflex gain was most
      evident at high stretch frequency suggesting a disproportionate loss of the large
      diameter afferent response and also increased reflex delay in the patients. These
      changes ensemble suggest significant loss of neural drive to the motor unit
      population. Patients also showed increased joint stiffness (measured as torque
      gain) in the contracting muscle, but there was no evidence of reflex activity or
      increased stiffness at rest. This suggests that the increased joint stiffness in
      RA was due to changes in the mechanical properties of the active muscle-joint
      system rather than changes in reflex properties.

PMID- 19771419
TI  - The weight of representing the body: addressing the potentially indefinite number
      of body representations in healthy individuals.
AB  - There is little consensus about the characteristics and number of body
      representations in the brain. In the present paper, we examine the main problems
      that are encountered when trying to dissociate multiple body representations in
      healthy individuals with the use of bodily illusions. Traditionally, task
      dependent bodily illusion effects have been taken as evidence for dissociable
      underlying body representations. Although this reasoning holds well when the
      dissociation is made between different types of tasks that are closely linked to
      different body representations, it becomes problematic when found within the same
      response task (i.e., within the same type of representation). Hence, this
      experimental approach to investigating body representations runs the risk of
      identifying as many different body representations as there are significantly
      different experimental outputs. Here, we discuss and illustrate a different
      approach to this pluralism by shifting the focus towards investigating task
      dependency of illusion outputs in combination with the type of multisensory
      input. Finally, we present two examples of behavioural bodily illusion
      experiments and apply Bayesian model selection to illustrate how this different
      approach of dissociating and classifying multiple body representations can be
      applied.

PMID- 19771420
TI  - The skin as a social organ.
AB  - In general, social neuroscience research tends to focus on visual and auditory
      channels as routes for social information. However, because the skin is the site
      of events and processes crucial to the way we think about, feel about, and
      interact with one another, touch can mediate social perceptions in various ways.
      This review situates cutaneous perception within a social neuroscience framework
      by discussing evidence for considering touch (and to some extent pain) as a
      channel for social information. Social information conveys features of
      individuals or their interactions that have potential bearing on future
      interactions, and attendant mental and emotional states. Here, we discuss
      evidence for an affective dimension of touch and explore its wider implications
      for the exchange of social information. We consider three important roles for
      this affective dimension of the cutaneous senses in the transmission and
      processing of social information: first, through affiliative behavior and
      communication; second, via affective processing in skin-brain pathways; and
      third, as a basis for intersubjective representation.

PMID- 19771421
TI  - Functional properties of low-threshold mechanoreceptive afferents in the human
      labial mucosa.
AB  - We used microneurography to investigate the functional properties of low
      threshold mechanoreceptive afferents innervating the oral mucosa of the inside of
      the lower lip. Impulse responses were recorded from the inferior alveolar nerve
      of four human subjects. The threshold force and receptive field boundaries were
      identified for 19 single mechanoreceptive afferents using thin filaments (von
      Frey hairs) that applied known forces to the mucosa. Most of the receptive fields
      were located close to the corners of the mouth. Twelve of the afferents were
      slowly adapting (SA) and the remaining seven units were fast adapting (FA). Two
      types of slowly adapting responses were observed, SA I and SA II. Four of the six
      SA II units were spontaneously active. The geometric mean value of the receptive
      field sizes was 4.20 mm(2) for the SA I units, 5.65 mm(2) for the SA II units,
      and 5.60 mm(2) for the FA I units. None of the FA afferents showed response
      properties characteristic of Pacinian-corpuscle type afferents (FA II units). All
      afferents showed low force threshold between 0.06 and 1 mN. The properties of the
      mechanoreceptors supplying the human labial mucosa appear more similar to those
      of the vermilion and facial skin of the lower lip than those supplying the mucosa
      of the dorsal tongue.

PMID- 19771423
TI  - Perineal US in the diagnosis of a prostatic utricle cyst in an infant.
AB  - The formation of a prostatic utricle cyst is a congenital abnormality in the
      involution of Mullerian ducts. This report describes an infant boy with bilateral
      epididymitis and a prostatic utricle cyst detected using a perineal US approach.
      According to our literature review, the use of US to detect this abnormality is
      rare. The perineal approach provides a better visualization of the cyst than the
      abdominal approach, and the relation between the cyst and the adjacent anatomic
      structures can be determined.

PMID- 19771422
TI  - Two mechanisms underlying inhibition of return.
AB  - Inhibition of return (IOR) refers to slower reaction times to targets presented
      at previously stimulated or inspected locations. Taylor and Klein (J Exp Psychol
      Hum Percept Perform 26(5):1639-1656, 2000) showed that IOR can affect either
      attentional/perceptual or motor processes, depending on whether the oculomotor
      system is in a quiescent or in an activated state, respectively. If the motoric
      flavour of IOR is truly non-perceptual and non-attentional, no IOR should be
      observed when the responses to targets are not based on spatial information. In
      the present experiments, we demonstrated that when the eyes moved to the
      peripheral cue and back to centre before the target appeared (to generate the
      motoric flavour), IOR was observed in detection tasks, for which the spatial
      location is an integral feature of the onset that is reported, but not in colour
      discrimination tasks, for which the outcome of a non-spatial perceptual
      discrimination is reported. When eye movements were prevented, both tasks showed
      robust IOR. We, therefore, conclude that the motoric flavour of IOR, elicited by
      oculomotor activation, does not affect attention or perceptual processing.

PMID- 19771424
TI  - A case of horseshoe lung and complex congenital heart disease in a term newborn.
AB  - We describe and illustrate a rare association of hypoplastic left heart syndrome,
      absent hilar left pulmonary artery, and an unusual bronchopulmonary malformation.
      This case highlights the utility of combination imaging of echocardiography and
      CT angiography in diagnosing a cyanotic newborn with a chest radiograph that is
      suspicious for lung hypoplasia.

PMID- 19771425
TI  - Adult onset glycogen storage disease type II (adult onset  Pompe disease): report
      and magnetic resonance images  of two cases.
AB  - Glycogen storage disease type II (GSDII), also referred to as Pompe disease or
      acid maltase deficiency, is a rare inherited condition caused by a deficiency in
      acid alpha-glucosidase (GAA) enzyme activity (Tinkle andLeslie. GeneReviews,
      2008. http://www.genetests.org). The condition is often classified by age of
      presentation,with infantile and late onset variants (Laforet et al. J Neurology
      55:1122-8, 2000). Late onset tends to present with progressive proximal muscle
      weakness and respiratory insufficiency (Winkel et al. J Neurology 252:875-84,
      2005). We report two cases of biopsy confirmed adulto nset GSDII, along with key
      Magnetic Resonance (MR) images.

PMID- 19771426
TI  - (186)Re-maSGS-Z (HER2:342), a potential Affibody conjugate for systemic therapy
      of HER2-expressing tumours.
AB  - PURPOSE: Affibody molecules are a novel class of tumour-targeting proteins, which
      combine small size (7 kDa) and picomolar affinities. The Affibody molecule
      Z(HER2:342) has been suggested for imaging of HER2 expression in order to select
      patients for trastuzumab therapy. When optimizing chelators for (99m)Tc
      labelling, we have found that synthetic Z(HER2:342) conjugated with
      mercaptoacetyl-glycyl-glycyl-glycyl (maGGG) and mercaptoacetyl-glycyl-seryl
      glycyl (maGSG) chelators provides relatively low renal uptake of radioactivity
      and could be suitable for therapy. METHODS: maGGG-Z(HER2:342) and maGSG
      Z(HER2:342) were labelled with (186)Re and their biodistribution was studied in
      normal mice. Dosimetric evaluation and tumour targeting to HER2-overexpressed
      xenografts (SKOV-3) by (186)Re-maGSG-Z(HER2:342) were studied. RESULTS: Gluconate
      mediated labelling of maGGG-Z(HER2:342) and maGSG-Z(HER2:342) with (186)Re
      provided a yield of more than 95% within 60 min. The conjugates were stable and
      demonstrated specific binding to HER2-expressing SKOV-3 cells. Biodistribution in
      normal mice demonstrated rapid blood clearance, low accumulation of radioactivity
      in the kidney and other organs, accumulating free perrhenate. Both (186)Re-maGGG
      Z(HER2:342) and (186)Re-maGSG-Z(HER2:342) demonstrated lower renal uptake than
      their (99m)Tc-labelled counterparts. (186)Re-maGSG-Z(HER2:342) provided the
      lowest uptake in healthy tissues. Biodistribution of (186)Re-maGSG-Z(HER2:342) in
      nude mice bearing SKOV-3 xenografts showed specific targeting of tumours. Tumour
      uptake 24 h after injection (5.84+/-0.54%ID/g) exceeded the concentration in
      blood by more than 500-fold, and uptake in kidneys by about 8-fold. Preliminary
      dosimetric evaluation showed that dose-to-tumour should exceed dose-to-kidney by
      approximately 5-fold. CONCLUSION: Optimization of chelators improves
      biodistribution properties of rhenium-labelled small scaffold proteins and
      enables selection of promising radiotherapeutic agents based on the Affibody
      molecule.

PMID- 19771427
TI  - CIMT 2009: report on the seventh annual meeting of the association for
      immunotherapy of cancer. June 3-5, Mainz, Germany.

PMID- 19771429
TI  - Inhibition of angiotensin II receptor 1 limits tumor-associated angiogenesis and
      attenuates growth of murine melanoma.
AB  - PURPOSE: We evaluated the involvement of angiotensin II (AngII)-dependent
      pathways in melanoma growth, through the pharmacological blockage of AT1 receptor
      by the anti-hypertensive drug losartan (LOS). RESULTS: We showed immunolabeling
      for both AngII and the AT1 receptor within the human melanoma microenvironment.
      Like human melanomas, we showed that murine melanomas also express the AT1
      receptor. Growth of murine melanoma, both locally and at distant sites, was
      limited in mice treated with LOS. The reduction in tumor growth was accompanied
      by a twofold decrease in tumor-associated microvessel density and by a decrease
      in CD31 mRNA levels. While no differences were found in the VEGF expression
      levels in tumors from treated animals, reduction in the expression of the VEGFR1
      (Flt-1) at the mRNA and protein levels was observed. We also showed
      downregulation of mRNA levels of both Flt-4 and its ligand, VEGF-C. CONCLUSIONS:
      Together, these results show that blockage of AT1 receptor signaling may be a
      promising anti-tumor strategy, interfering with angiogenesis by decreasing the
      expression of angiogenic factor receptors.

PMID- 19771428
TI  - Additive effects of drug transporter genetic polymorphisms on irinotecan
      pharmacokinetics/pharmacodynamics in Japanese cancer patients.
AB  - PURPOSE: Effects of genetic polymorphisms/variations of ABCB1, ABCC2, ABCG2 and
      SLCO1B1 in addition to "UGT1A1*28 or *6" on irinotecan
      pharmacokinetics/pharmacodynamics in Japanese cancer patients were investigated.
      METHODS: Associations between transporter haplotypes/variations along with
      UGT1A1*28 or *6 and SN-38 area under the time-concentration curve (AUC) or
      neutropenia were examined in irinotecan monotherapy (55 patients) and irinotecan
      cisplatin-combination therapy (62 patients). RESULTS: Higher SN-38 AUC values
      were observed in ABCB1 2677G>T (A893S) (*2 group) for both regimens. Associations
      of grade 3/4 neutropenia were observed with ABCC2 -1774delG (*1A), ABCG2 421C>A
      (Q141K) and IVS12 + 49G>T ((#) IIB) and SLCO1B1 521T>C (V174A) (*15 x 17) in the
      irinotecan monotherapy, while they were evident only in homozygotes of ABCB1*2,
      ABCG2 (#) IIB, SLCO1B1*15 x 17 in the cisplatin-combination therapy. With
      combinations of haplotypes/variations of two or more genes, neutropenia incidence
      increased, but their prediction power for grade 3/4 neutropenia is still
      unsatisfactory. CONCLUSIONS: Certain transporter genotypes additively increased
      irinotecan-induced neutropenia, but their clinical importance should be further
      elucidated.

PMID- 19771430
TI  - Gef gene therapy enhances the therapeutic efficacy of doxorubicin to combat
      growth of MCF-7 breast cancer cells.
AB  - PURPOSE: The potential use of combined therapy is under intensive study including
      the association between classical cytotoxic and genes encoding toxic proteins
      which enhanced the antitumour activity. The main aim of this work was to evaluate
      whether the gef gene, a suicide gene which has a demonstrated antiproliferative
      activity in tumour cells, improved the antitumour effect of chemotherapeutic
      drugs used as first-line treatment in the management of advanced breast cancer.
      METHODS: MCF-7 human breast cancer cells were transfected with gef gene using
      pcDNA3.1-TOPO expression vector. To determine the effect of the combined therapy,
      MCF-7 transfected and non-transfected cells were exposed to paclitaxel, docetaxel
      and doxorubicin at different concentrations. The growth-inhibitory effect of gef
      gene and/or drugs was assessed by MTT assay. Apoptosis modulation was determined
      by flow cytometric analysis, DNA fragmentation and morphological analysis.
      Multicellular tumour spheroids (MTS) from MCF-7 cells were used to confirm
      effectiveness of combined therapy (gef gene and drug). RESULTS: Our results
      demonstrate that combined therapy gef gene/drugs (paclitaxel, docetaxel or
      doxurubicin) caused a decrease in cell viability. However, only the gef
      doxorubicin (10 microM) combination induced a greater enhancement in the
      antitumour activity in MCF-7 cells. Most importantly, this combined strategy
      resulted in a significant synergistic effect, thus allowing lower doses of the
      drug to be used to achieve the same therapeutic effect. These results were
      confirmed using MTS in which volume decrease with combined therapy was greater
      than obtained using the gene therapy or chemotherapy alone, or the sum of both
      therapies. CONCLUSIONS: The cytotoxic effect of gef gene in breast cancer cells
      enhances the chemotherapeutic effect of doxorubicin. This therapeutic approach
      has the potential to overcome some of the major limitations of conventional
      chemotherapy, and may therefore constitute a promising strategy for future
      applications in breast cancer therapy.

PMID- 19771431
TI  - A phase-II study of combination of pegylated interferon alfa-2a and capecitabine
      in locally advanced or metastatic renal cell cancer.
AB  - PURPOSE: Combination of capecitabine and interferon has shown activity in
      metastatic renal cell carcinoma. Pegylated interferons might have more clinical
      activity and fewer side effects. This study evaluated the efficacy, tolerability,
      and safety of the combination of capecitabine and pegylated interferon alfa-2a.
      METHODS: In this open label, single institution, non-randomized phase-II first
      line study, 26 patients were included. Capecitabine was administered 2,000
      mg/m(2) daily for 14 days followed by 1 week rest. Pegylated interferon alfa-2a
      was given once as weekly injections with a fixed dose of 180 microg. Overall
      survival, progression-free survival, and response rates were evaluated; safety
      and tolerability were monitored. RESULTS: Response rate was 27, with 4% complete
      responses. Stable disease was achieved in 42%. The treatment discontinued in 4
      (15%) patients before first response evaluation because of toxicity. The median
      progression-free survival was 7.5 months; the median overall survival was 17
      months. Grades 3-4 toxicity was seen in 46% of patients, but in 93% of cycles no
      serious toxicity was experienced. Dose reductions had to be done, but in 81% of
      cycles intensity of 70% or more was possible. Quality of life was better in cycle
      five than in the base line. CONCLUSIONS: The combination had moderate, but
      manageable toxicity. In the future studies, lower dose for capecitabine is
      recommended. The combination was active and the response rates seen here were in
      line with phase-II studies on former combinations of non-pegylated interferons.
      One complete remission was achieved.

PMID- 19771432
TI  - Heterogeneity of epithelial and stromal cells of head and neck squamous cell
      carcinomas in ex vivo chemoresponse.
AB  - BACKGROUND: Valid prediction of the effectiveness of chemotherapeutic agents in
      individual head and neck squamous cell carcinoma (HNSCC) is desirable and might
      be achieved using ex vivo assays. METHODS: Three biopsies from each of 15 HNSCC
      were taken, minced and digested by collagenase. The digested HNSCC was added to
      serial dilutions of either cisplatin (CIS) or docetaxel (DTX), which were
      prepared under flavin-protecting conditions in ECM-coated microtiterplates. After
      72-h incubation, cultures were methanol-fixed and Giemsa-stained. The cutoff
      concentration (COC; concentration completely suppressing colony formation) for
      epithelial cells (EC) and stromal cells (SC) was evaluated. RESULTS: 12/15 HNSCC
      (80%) were evaluable. Despite significant correlation of COC of CIS in respect of
      colony formation of EC or SC, no significant differences in response of
      individual HNSCC specimens were found in the t test for paired samples (p >
      0.16). The same applied to DTX. However, EC and SC showed heterogeneity in
      chemoresponses leading to COC variability of more than one titration step in
      44.1% (CIS) and 20% of HNSCC (DTX). No significant correlation between the COC of
      both cell populations was found in HNSCC specimens. CONCLUSIONS: The ex vivo
      chemoresponse of EC and SC of HNSCC must be analyzed separately.

PMID- 19771433
TI  - Daphnia revisited: local stability and bifurcation theory for physiologically
      structured population models explained by way of an example.
AB  - We consider the interaction between a general size-structured consumer population
      and an unstructured resource. We show that stability properties and bifurcation
      phenomena can be understood in terms of solutions of a system of two delay
      equations (a renewal equation for the consumer population birth rate coupled to a
      delay differential equation for the resource concentration). As many results for
      such systems are available (Diekmann et al. in SIAM J Math Anal 39:1023-1069,
      2007), we can draw rigorous conclusions concerning dynamical behaviour from an
      analysis of a characteristic equation. We derive the characteristic equation for
      a fairly general class of population models, including those based on the
      Kooijman-Metz Daphnia model (Kooijman and Metz in Ecotox Env Saf 8:254-274, 1984;
      de Roos et al. in J Math Biol 28:609-643, 1990) and a model introduced by Gurney
      Nisbet (Theor Popul Biol 28:150-180, 1985) and Jones et al. (J Math Anal Appl
      135:354-368, 1988), and next obtain various ecological insights by analytical or
      numerical studies of special cases.

PMID- 19771434
TI  - Bone density in patients with chondromalacia patella.
AB  - Chondromalacia of the patella is the most common cause of anterior knee pain in
      young women. The etiology of the disease is not well-understood but the initial
      lesion is a disorganization of collagenous structures. Since the disease is
      proposed to be due to generalized constitutional disturbance, we postulated that
      bony structures could also be involved. To investigate this hypothesis we
      measured the bone density of 286 patients with the diagnosis of chondromalacia of
      the patella during a 4-year period using dual energy X-ray absorptiometry (DXA)
      method. We found a significant number of patients having low bone densities. This
      problem was more pronounced in men and in younger age groups. We suggest base
      line bone density evaluation in all patients, treatment of osteopenia or
      osteoporosis in select patients and regular follow-ups using DXA.

PMID- 19771436
TI  - Spondylodiscitis in the elderly patient: clinical mid-term results and quality of
      life.
AB  - INTRODUCTION: Focusing on spondylodiscitis in elderly patients current literature
      does not contain much information. METHOD: We performed a retrospective case
      series (n = 32) comparing conservative (group 1; n = 16) versus operative (group
      2; n = 16) treated spondylodiscitis patients aged > or =65 years (mean age 74.9
      years) from January 2002 to April 2004. The review of the medical records
      provided information about the pre-hospital time, the inpatient course and the
      time after discharge. At follow-up (FU) (mean 3.6 years) disease specific and
      general quality of life (QOL) questionnaires (COMI back patient self-assessment,
      ODI and SF-36) were administered. RESULTS: Altogether, 71.9% of the patients
      could be contacted; 12.5% had died since hospitalisation and 15.6% could not be
      contacted anymore. At FU based on the visual analogue scale, patients indicated
      an average of 3.2 for back pain and 2.5 for leg pain. ODI scoring yielded minimal
      disability for 38.9%, a moderate disability for 22.2%, a severe disability for
      22.2% and for 11.1% a crippled situation; 5.6% were bed-ridden or exaggerated
      their symptoms. The SF-36 PCS amounted to an average of 38.2, the MCS 50.6. Owing
      to additional surgery-associated risks, operative treatment of spondylodiscitis
      feature a complication rate twice as high in the respective group, but general
      complications do not differ. At FU, no statistically remarkable difference
      concerning QOL and remaining pain became evident between the groups, the operated
      patients being more satisfied with regard to the treatment of spondylodiscitis.
      CONCLUSION: Ultimately, if surgery is indicated the operative risks should be
      borne in mind, but advanced age should not be the crucial factor in decision
      making.

PMID- 19771438
TI  - High sensitive serum C-reactive protein and its relationship with other
      cardiovascular risk factors in normoinsulinemic polycystic ovary patients without
      metabolic syndrome.
AB  - PURPOSE: The aims of the study were to investigate high sensitive serum C
      reactive protein (HS-CRP) levels in normoinsulinemic polycystic ovary syndrome
      (PCOS) patients without metabolic syndrome and whether there was any relationship
      between HS-CRP and other cardiovascular risk factors such as obesity and serum
      lipids. METHODS: A total of 52 normoinsulinemic PCOS women without metabolic
      syndrome and 48 normoandrogenic ovulatory women were enrolled in the study.
      Standard clinical examinations, and ultrasonographic and endocrine screening
      including FSH, LH, total testosterone, free testosterone, sex hormone-binding
      globulin, dehydroepiandrosterone sulfate, low-density lipoprotein (LDL), high
      density lipoprotein (HDL), total cholesterol (TC) and triglyceride (TG) were
      measured. Normal insulin sensitivity was defined on the basis of fasting serum
      glucose and insulin levels, serum insulin response to an oral glucose tolerance
      test and homeostatic model of insulin resistance. HS-CRP was assessed
      spectrophotometrically. RESULTS: PCOS patients had increased HS-CRP compared to
      the control group (P < 0.0001). HS-CRP was positively correlated with body mass
      index (BMI) (r = 0.44, P < 0.0001), waist-to-hip ratio (WHR) (r = 0.66, P <
      0.0001), LDL (r = 0.62, P < 0.0001), TC (r = 0.56, P < 0.0001) and TG (r = 0.38,
      P < 0.0001), and negatively correlated with HDL (r = -0.45, P < 0.0001). There
      was also a strong association between HS-CRP and PCOS status (r = 0.69, P <
      0.0001) in the study. Multivariate regression analysis demonstrated that BMI,
      WHR, LDL, HDL and PCOS status were also the independent variables that influenced
      HS-CRP in the overall group. CONCLUSION: Elevated HS-CRP was associated with
      cardiovascular risk factors in normoinsulinemic PCOS without metabolic syndrome.
      These patients need more intensive screening or treatment for this disease.

PMID- 19771439
TI  - Ovarian tissue cryopreservation for non-malignant indications.
AB  - BACKGROUND: Ovarian tissue cryopreservation (OTC) is not restricted to patients
      suffering from malignancies. Benign haematopoietic diseases such as autoimmune
      diseases and others have been mentioned to be feasible indications. The aim of
      our study was to demonstrate that surgery for OTC is a safe procedure for
      fertility preservation in patients with non-malignant diseases. METHODS: In a
      retrospective cohort study intra- and postoperative courses were evaluated.
      Histological examination of one random ovarian cortical slice was performed to
      determine the presence of primordial follicles. Immediately after the excision,
      microbiological culture techniques from swabs were taken from all slices.
      RESULTS: Seven of 85 patients (8.2%) have undergone surgery for OTC for non
      malignant indications. All patients had an uncomplicated intraoperative course. A
      median number of 12 cortical stripes were excised and cryopreserved (range 7-17).
      Only for one patient an adverse event was found which was not related to
      laparoscopy for OTC. All patients having undergone routine laparoscopy for OTC
      only could be released from hospital on the first postoperative day. Selective
      microbiological tests showed negative results in all cases. Histological
      examinations revealed intact ovarian tissue with primordial follicles in 6/7
      patients. CONCLUSION: Whether surgery for OTC in patients with non-malignant
      indications is feasible from an ethical point of view remains open. However,
      laparoscopy for ovarian tissue harvesting is a safe procedure for patients
      undergoing cytotoxic treatment for benign diseases.

PMID- 19771440
TI  - Definitive chemotherapy: a new frontier in the fight against laryngeal cancer.

PMID- 19771441
TI  - One-stage reconstruction of the entire upper lip and the columella with a
      modified bilateral nasolabial flap.
AB  - The functional and cosmetic reconstruction of the upper lip after a subtotal
      defect is a highly demanding challenge, especially when the columella is
      involved. In the majority of cases, the surgical techniques described in the
      literature are suitable only for restoring the function and appearance of the
      upper lip but not for reconstructing adjacent areas. In this article, we present
      the case of an 85-year-old female patient with an extensive, aggressive and
      highly invasive basal cell carcinoma of the upper lip and the columella. We
      describe a modification of the nasolabial flap technique using cheek tissue for
      the reconstruction of the defect. The modified flap is used for both the full
      thickness reconstruction of the subtotal upper-lip defect and the restoration of
      the function and appearance of the columella. This technique allows excellent
      cosmetic and functional results to be obtained in a single-stage procedure.

PMID- 19771442
TI  - Tympanosclerosis and our surgical results.
AB  - Tympanosclerosis is a sequel of chronic otitis media characterized by the
      deposition of calcareous plaques following hyaline degeneration in the fibrous
      layer of the tympanic membrane and inside middle ear mucosa. It usually results
      from prior middle ear infections. In this study, results of treatment and
      clinical findings of the patients with tympanosclerosis are presented. Our
      objective is to determine the changes in middle ear caused by tympanosclerosis
      and intervene in the more problematic zone and find out the more useful treatment
      protocol for patients. Preoperative features, middle ear findings detected during
      surgery and postoperative hearing levels of the patients who were operated in our
      clinic between January 1996 and June 2006 due to tympanosclerosis were evaluated.
      Surgical treatment was performed on a total of 37 patients including 25 females
      and 12 males between ages of 11 and 71. Preoperative tympanic membranes
      perforations were presented at a rate of 91% and average airway bone gap was 37.8
      dB. Bilateral involvement was present in 59%. Conductive-type hearing loss was
      present at a rate of 81%, whereas mixed-type hearing existed at a rate of 19%.
      Sclerotic plaques were most commonly localized in the attic with a rate of 72%.
      Post-op outcome was found to be 27% in the patients with air bone gap between 0
      20 dB. The best hearing result belonged to type 1 patients. Cases in which stapes
      footplate was fixated had the worst result in terms of hearing. Teflon piston was
      only applied in one patient. Our tympanoplasty success was found to be 67%. The
      most common treatment method of tympanosclerosis is surgery. Stapedectomy is
      recommended in surgery instead of mobilization techniques. However, there is
      often recurrence and there is no curative treatment. Therefore rehabilitation
      with hearing device can be preferred as an adjunct. In the recent experimental
      studies, good results with topical or systemic agents have also been promising.

PMID- 19771443
TI  - Complementary and alternative medicine use by otolaryngology patients: a paradigm
      for practitioners in all surgical specialties.
AB  - There is growing interest in complementary and alternative medicine (CAM) amongst
      the general population. Little information is available on CAM use in
      otolaryngology patients in the UK. Despite concerns over safety, efficacy and
      cost-effectiveness, CAM use is common amongst ENT patients. Patients perceive
      these medications as possible boosters to their immune system. It is becoming
      increasingly important that health care providers in all specialties ask their
      patients about CAM use and are aware of the implications it carries. The
      objective is to study the prevalence and pattern of CAM use among adult and
      paediatric ENT patients in a UK teaching hospital. A cross-sectional study was
      done by sending anonymous questionnaire to all outpatient and elective inpatients
      over a 3-month period. Response rate was 73% (1,789/2,440). Prominent
      demographics: female, married, over-50 s. Sixty percent had used CAM, 35% in last
      year. Most common herbs: cod liver oil (n = 481), garlic (n = 255), cranberry (n
      = 224); non-herbal: massage (n = 287), acupuncture (n = 233), aromatherapy (n =
      170). Most commonly cited reasons for using CAM: general health, enhanced
      immunity and prevention/treatment of common illnesses like the common cold,
      asthma and bodily aches and pains.

PMID- 19771446
TI  - Influence of motor unit synchronization on amplitude characteristics of surface
      and intramuscularly recorded EMG signals.
AB  - The increase in muscle strength without noticeable hypertrophic adaptations is
      very important in some sports. Motor unit (MU) synchronisation and higher rate of
      MU activation are proposed as possible mechanisms for such a strength and
      electromyogram (EMG) increase in the early phase of a training regimen. Root mean
      square and/or integrated EMG are amplitude measures commonly used to estimate the
      adaptive changes in efferent neural drive. EMG amplitude characteristics could
      change also because of alteration in intracellular action potential (IAP) spatial
      profile. We simulated MUs synchronization under different length of the IAP
      profile. Different synchronization was simulated by variation of the percent of
      discharges in a referent MU, to which a variable percent of remaining MUs was
      synchronized. Population synchrony index estimated the degree of MU
      synchronization in EMG signals. We demonstrate that the increase in amplitude
      characteristics due to MU synchronization is stronger in surface than in
      intramuscularly detected EMG signals. However, the effect of IAP profile
      lengthening on surface detected EMG signals could be much stronger than that of
      MU synchronization. Thus, changes in amplitude characteristics of surface
      detected EMG signals with progressive strength training could hardly be used as
      an indicator of changes in neural drive without testing possible changes in IAPs.

PMID- 19771447
TI  - Exercise-induced extracellular 72 kDa heat shock protein (Hsp72) stimulates
      neutrophil phagocytic and fungicidal capacities via TLR-2.
AB  - This study evaluated the role of toll like receptor 2 (TLR-2) in the interaction
      of 72 kDa extracellular heat shock protein (Hsp72, a stress-inducible protein)
      with neutrophils and the participation on TLR-2 in the stimulation of neutrophil
      phagocytic and fungicidal capacities by post-exercise physiological
      concentrations of Hsp72. Human peripheral blood neutrophils were incubated with
      fluorescein isothiocyanate-conjugated Hsp72, and were analyzed by
      immunofluorescence microscopy and flow cytometry. Both methods revealed an
      interaction of Hsp72 with neutrophils. In addition, when neutrophils were pre
      incubated with an anti-TLR-2 antibody this interaction was clearly decreased.
      Post-exercise circulating concentration of Hsp72 (8.6 ng/ml) stimulated the
      phagocytic and fungicidal capacities of neutrophils and this effect could be also
      blocked using an antibody against TLR-2. Phosphatidylinositol-3-kinase (PI3K),
      extracellular signal-regulated kinase (ERK) and the nuclear transcription factor
      kappa beta (NF-kappabeta) were found to be involved in the signaling process,
      confirming the participation of TLR-2 in the stimulation of neutrophil function
      by Hsp72. In conclusion, TLR-2 is involved at least in part, in the stimulation
      of neutrophil phagocytic and fungicidal capacities induced by post-exercise
      physiological concentrations of Hsp72.

PMID- 19771448
TI  - Influence of crank length on cycle ergometry performance of well-trained female
      cross-country mountain bike athletes.
AB  - The aim of this study was to determine the differential effects of three commonly
      used crank lengths (170, 172.5 and 175 mm) on performance measures relevant to
      female cross-country mountain bike athletes (n = 7) of similar stature. All
      trials were performed in a single blind and balanced order with a 5- to 7-day
      period between trials. Both saddle height and fore-aft position to pedal axle
      distance at a crank angle of 90 degrees was controlled across all trials. The
      laboratory tests comprised a supra-maximal (peak power-cadence); an isokinetic
      (50 rpm) test; and a maximal test of aerobic capacity. The time to reach supra
      maximal peak power was significantly (P < 0.05) shorter in the 170 mm (2.57 +/-
      0.79 s) condition compared to 175 mm (3.29 +/- 0.76 s). This effect represented a
      mean performance advantage of 27.8% for 170 mm compared to 175 mm. There was no
      further inter-condition differences between performance outcome measurements
      derived for the isokinetic (50 rpm) maximum power output, isokinetic (50 rpm)
      mean power output or indices of endurance performance. The decreased time to peak
      power with the greater rate of power development in the 170 mm condition suggests
      a race advantage may be achieved using a shorter crank length than commonly
      observed. Additionally, there was no impediment to either power output produced
      at low cadences or indices of endurance performance using the shorter crank
      length and the advantage of being able to respond quickly to a change in terrain
      could be of strategic importance to elite athletes.

PMID- 19771449
TI  - Exponential protocols for cardiopulmonary exercise testing on treadmill and cycle
      ergometer.
AB  - An extended exponential exercise protocol was validated by comparing submaximal
      and maximal parameters with those obtained by linear protocol. Normal subjects (n
      = 16, 20-69 years) undertook maximal exercise tests on treadmill and cycle
      ergometer. The subjects had a wide range of exercise capacity, and all were
      accommodated by the protocol. Mean oxygen uptake (V(O2)) agreed between protocols
      at gas exchange anaerobic threshold (theta) (95% CI of difference -0.1 to +0.06 l
      min(-1)) and at peak (95% CI of difference -0.1 to +0.1 l min(-1)). Mean pre
      thetaDeltaV(O2)/Deltawork rate (W) slope on the cycle ergometer agreed between
      protocols (95% CI of the difference -0.9 to +0.25 ml min(-1) W(-1)). Post
      thetaDeltaV(O2)/DeltaW slope was steeper than pre-theta, and steeper by linear
      than by exponential protocol (P = 0.0001). It is concluded that the exponential
      protocol is valid for the measurement of submaximal and maximal exercise
      parameters in subjects with a wide range of exercise capacity.

PMID- 19771450
TI  - The histone acetyltransferase GCN5 affects the inflorescence meristem and stamen
      development in Arabidopsis.
AB  - A central question in biology is to understand how gene expression is precisely
      regulated to give rise to a variety of forms during the process of development.
      Epigenetic effects such as DNA methylation or histone modification have been
      increasingly shown to play a critical role in regulation of genome function. GCN5
      is a prototypical histone acetyltransferase that participates in regulating
      developmental gene expression in several metazoan species. In Arabidopsis
      thaliana, plants with T-DNA insertions in GCN5 (also known as HAG1) display a
      variety of pleiotropic effects including dwarfism, loss of apical dominance, and
      floral defects affecting fertility. We sought to determine when during early
      development floral abnormalities first arise. Using scanning electron microscopy,
      we demonstrate that gcn5-1/hag1-1 and gcn5-5/hag1-5 mutants display
      overproliferation of young buds and development of abnormal structures around the
      inflorescence meristem. gcn5 mutants also display defects in stamen number and
      arrangement at later stages. This analysis provides temporal and spatial
      information to aid in the identification of GCN5 target genes in the developing
      flower. Preliminary studies of putative targets using reverse transcriptase PCR
      suggest that the floral meristem identity gene LEAFY is among factors upregulated
      in gcn5-1 mutants.

PMID- 19771451
TI  - Anaphylaxis during skin testing with food allergens in children.
AB  - Skin testing is the diagnostic cornerstone for allergies and is considered
      extremely safe. It is usually performed with the prick and the prick-to-prick
      method. The aim of this study is to report the first two pediatric cases of
      systemic allergic reactions during skin prick tests (SPT) with commercial food
      allergens. Both patients had a history of fish allergy. A 5-year-old girl, with a
      history of atopic dermatitis and asthma, reported an episode of urticaria and
      angioedema due to ingestion of fish, which had occurred 2 years before
      consultation. Ten minutes after having completed SPT to fish extracts, which had
      resulted positive, she suffered from generalized pruritus, nausea, stomach pain,
      and loss of consciousness. A 9-year-old boy, with a history of asthma and two
      episodes of acute urticaria and angioedema upon eating fish during infancy,
      reported a recent episode of oropharyngeal pruritus after tasting salmon. He was
      evaluated for fish allergy with SPT but developed conjunctivitis and acute
      urticaria during the first 10 min of the test. Anaphylaxis appears to be a rare
      side effect of skin testing in pediatric patients. Children with a history of
      asthma and atopic dermatitis are more likely to react.

PMID- 19771452
TI  - Variants in toll-like receptors 2 and 9 influence susceptibility to pulmonary
      tuberculosis in Caucasians, African-Americans, and West Africans.
AB  - Tuberculosis (TB) is a global public health problem and a source of preventable
      deaths each year, with 8.8 million new cases of TB and 1.6 million deaths
      worldwide in 2005. Approximately, 10% of infected individuals develop pulmonary
      or extrapulmonary TB, suggesting that host defense factors influence development
      of active disease. Toll-like receptor' (TLR) polymorphisms have been associated
      with regulation of TLR expression and development of active TB. In the present
      study, 71 polymorphisms in TLR1, TLR2, TLR4, TLR6, and TLR9 were examined from
      474 (295 cases and 179 controls) African-Americans, 381 (237 cases and 144
      controls) Caucasians, and from 667 (321 cases and 346 controls) Africans from
      Guinea-Bissau for association with pulmonary TB using generalized estimating
      equations and logistic regression. Statistically significant associations were
      observed across populations at TLR9 and TLR2. The strongest evidence for
      association came at an insertion (I)/deletion (D) polymorphism (-196 to -174) in
      TLR2 that associated with TB in both Caucasians (II vs. ID&DD, OR = 0.41 [95% CI
      0.24-0.68], p = 0.0007) and Africans (II vs. ID&DD, OR = 0.70 [95% CI 0.51-0.95],
      p = 0.023). Our findings in three independent population samples indicate that
      variations in TLR2 and TLR9 might play important roles in determining
      susceptibility to TB.

PMID- 19771453
TI  - Energetic cost of bot fly parasitism in free-ranging eastern chipmunks.
AB  - The energy and nutrient demands of parasites on their hosts are frequently
      invoked as an explanation for negative impacts of parasitism on host survival and
      reproductive success. Although cuterebrid bot flies are among the physically
      largest and most-studied insect parasites of mammals, the only study conducted on
      metabolic consequences of bot fly parasitism revealed a surprisingly small effect
      of bot flies on host metabolism. Here we test the prediction that bot fly
      parasitism increases the resting metabolic rate (RMR) of free-ranging eastern
      chipmunks (Tamias striatus), particularly in juveniles who have not previously
      encountered parasites and have to allocate energy to growth. We found no effect
      of bot fly parasitism on adults. In juveniles, however, we found that RMR
      strongly increased with the number of bot fly larvae hosted. For a subset of 12
      juveniles during a year where parasite prevalence was particularly high, we also
      compared the RMR before versus during the peak of bot fly prevalence, allowing
      each individual to act as its own control. Each bot fly larva resulted in a
      approximately 7.6% increase in the RMR of its host while reducing juvenile growth
      rates. Finally, bot fly parasitism at the juvenile stage was positively
      correlated with adult stage RMR, suggesting persistent effects of bot flies on
      RMR. This study is the first to show an important effect of bot fly parasitism on
      the metabolism and growth of a wild mammal. Our work highlights the importance of
      studying cost of parasitism over multiple years in natural settings, as negative
      effects on hosts are more likely to emerge in periods of high energetic demand
      (e.g. growing juveniles) and/or in harsh environmental conditions (e.g. low food
      availability).

PMID- 19771454
TI  - Spatial heterogeneity confounded ozone-exposure experiment in semi-natural
      grassland.
AB  - Interpretation of observations from manipulative experiments is often complicated
      by a multitude of uncontrolled processes operating at various spatial and
      temporal scales. As such processes may differ among experimental plots there is a
      risk that effects of experimental treatments are confounded. Here we report on a
      free-air ozone-exposure experiment in permanent semi-natural grassland that
      suggested strong ozone effects on community productivity after 5 years. We tested
      ozone effects and investigated the potential of confounding due to changes in
      nutrient management. Repeated-measure ANOVA revealed mainly negative temporal
      trends for frequency of abundant productive plant species. Constrained ordination
      additionally showed converging trajectories of species compositions for ozone and
      control treatments with time. Yields sampled prior to the start of the experiment
      and soil nitrogen concentrations revealed that spatial heterogeneity in the soil
      nutrient status was not accounted for by the random allocation of treatments to
      plots with a bias towards less productive patches in the elevated-ozone plots. Re
      analysis of yield data using repeated-measure ANOVA with a covariable to account
      for productivity prior to the start of fumigation revealed effects on the
      temporal changes in total yield and yield of legumes that cannot be separated
      between ozone and pre-treatment nutrient status. Changes in species composition
      favour an ecological interpretation with spatial heterogeneity as the major cause
      of different yield declines. Although elevated ozone may cause subtle
      physiological changes with longer term implications, our new results suggest that
      species-rich mature grassland such as the one studied at Le Mouret may be less
      sensitive to elevated ozone than previously assumed. In this experiment a
      confounded design was hidden at the start by transitory effects of a prior change
      in nutrient treatments.

PMID- 19771455
TI  - The association between isoinertial trunk muscle performance and low back pain in
      male adolescents.
AB  - The literature reports inconsistent findings regarding the association between
      low back pain (LBP) and trunk muscle function, in both adults and children. The
      strength of the relationship appears to be influenced by how LBP is qualified and
      the means by which muscle function is measured. The aim of this study was to
      examine the association between isoinertial trunk muscle performance and
      consequential (non-trivial) low back pain (LBP) in male adolescents. Healthy male
      adolescents underwent anthropometric measurements, clinical evaluation, and tests
      of trunk range of motion (ROM), maximum isometric strength (STRENGTH) and peak
      movement velocity (VEL), using an isoinertial device. They provided information
      about their regular sporting activities, history and family history of LBP.
      Predictors of "relevant/consequential LBP" were examined using multivariable
      logistic regression. LBP status was reassessed after 2 years and the change from
      baseline was categorised. At baseline, 33/95 (35%) subjects reported having
      experienced consequential LBP. BMI, a family history of LBP, and regularly
      playing sport were each significantly associated with a history of consequential
      LBP (p < 0.05). 85/95 (89%) boys participated in the follow-up: 51 (60%) reported
      no LBP at either baseline or follow-up (never LBP); 5 (6%) no LBP at baseline,
      but LBP at follow-up (new LBP); 19 (22%) LBP at baseline, but none at follow-up;
      and 10 (12%) LBP at both time-points (recurrent/persistent LBP). The only
      distinguishing features of group membership in these small groups were: fewer
      sport-active in the "never LBP" group); worse trunk mobility, in the "persistent
      LBP" group, lower baseline sagittal ROM in the "never LBP" and "new LBP" (p <
      0.05). Regular involvement in sport was a consistent predictor of LBP.
      Isoinertial trunk performance was not associated with LBP in adolescents.

PMID- 19771457
TI  - Do anvil-using banded mongooses understand means-end relationships? A field
      experiment.
AB  - Tool use and the associated need to choose appropriate objects for a particular
      task are thought to have selected for specialized cognitive abilities such as
      means-end comprehension. Several studies on large-brained tool-using primates and
      birds have demonstrated understanding of causal relationships to some extent.
      However, a comprehensive appraisal of this hypothesis requires testing for means
      end comprehension also in non-tool-users as well as in small-brained tool users.
      Moreover, the results of captive studies do not answer the question whether such
      cognitive abilities are relevant to an animal in its natural environment. Here I
      presented wild banded mongooses Mungos mungo, small-brained carnivores that
      regularly use anvils to open food items with a hard shell, with a transfer test
      involving novel anvil objects. I found no evidence for means-end comprehension or
      a heuristic strategy used for anvil choice in this species. Instead, recognition
      of suitable anvils appears to be learned by trial and error separately for
      different categories of anvils. These data suggest that, at least for the anvil
      choice task investigated here, the need to choose suitable objects has not
      selected for specialized cognitive abilities in banded mongooses, a finding that
      may extend to a large range of proto-tool users. Furthermore, this study adds to
      growing evidence that animals subjected to the selection pressures and trade-offs
      of their natural environment may get by with cognitively more simple strategies
      than sometimes suggested by captive studies or plausibility arguments.

PMID- 19771456
TI  - Copper and zinc bis(thiosemicarbazonato) complexes with a fluorescent tag:
      synthesis, radiolabelling with copper-64, cell uptake and fluorescence studies.
AB  - The synthesis of new copper(II) bis(thiosemicarbazonato) complexes with an
      appended pyrene chromophore and their zinc(II) analogues is reported. The new
      proligands and their copper(II) and zinc(II) complexes were characterised by a
      combination of NMR, EPR, high performance liquid chromatography, mass
      spectrometry, electronic spectroscopy and electrochemical measurements. The new
      copper(II) complexes are fluorescent as a consequence of an appended pyrene
      substituent that is separated from the sulphur coordinating to the metal ion by
      five bonds. The emission from the pyrene substituent is concentration- and
      solvent-dependent with characteristic formation of excimer aggregates. A
      radioactive (64)Cu complex has been prepared. Cell permeability, intracellular
      distribution and importantly the ability to cross the nuclear membrane to target
      DNA were investigated using confocal fluorescence microscopy in a human cancer
      cell line under normal oxygen conditions and hypoxic conditions. In both cases,
      there was no evidence of uptake of the copper(II) bis(thiosemicarbazonato)
      complexes in the area of the cell nucleus.

PMID- 19771458
TI  - Health impairments and labour market outcomes.
AB  - Our analysis is based on the 2008 Athens Area Study and exploits detailed
      information regarding health impairments and labour market outcomes for Greek
      males. Distinguishing between healthy and heath-impaired employees who have or do
      not have work limitations, the unobserved productivity effect of health is
      separated from discrimination. We then estimate a regression model that includes
      terms to correct for employment selection and endogenous stratification of self
      reported health condition. A penalty for productivity limitation exists. Evidence
      of wage discrimination is also found. Both findings are statistically significant
      and highlight the necessity for instituting active policies against unequal
      treatment.

PMID- 19771459
TI  - Cardiac volumetry in patients with heart failure and reduced  ejection fraction:
      a comparative study correlating multi-slice  computed tomography and magnetic
      resonance tomography.  Reasons for intermodal disagreement.
AB  - BACKGROUND: In humans with normal hearts multi-slice computed tomography (MSCT)
      based volumetry was shown to correlate well with the gold standard, cardiac
      magnetic resonance imaging (CMR). We correlated both techniques in patients with
      various degrees of heart failure and reduced ejection fraction (HFREF) resulting
      from cardiac dilatation. METHODS: Twenty-four patients with a left ventricular
      enddiastolic volume (LV-EDV) of C 150 ml measured by angiography underwent MSCT
      and CMR scanning for left and right ventricular (LV, RV) volumetry. MSCT based
      short cardiac axis views were obtained beginning at the cardiac base advancing to
      the apex. These were reconstructed in 20 different time windows of the RR
      interval (0-95%) serving for identification of enddiastole (ED) and end-systole
      (ES) and for planimetry. ED and ES volumes and the ejection fraction (EF) were
      calculated for LV and RV. MSCT based volumetry was compared with CMR. RESULTS:
      MSCT based LV volumetry significantly correlates with CMR as follows: LV-EDV r =
      0.94, LV-ESV r = 0.98 and LV-EF r = 0.93, but significantly overestimates LV-EDV
      and LV-ESV and underestimates EF (P ? 0.0001). MSCT based RV volumetry
      significantly correlates with CMR as follows: RV-EDV r = 0.79, RVESV r = 0.78 and
      RV-EF r = 0.73, but again significantly overestimates RV-EDV and RV-ESV and
      underestimates RV-EF (P ? 0.0001). CONCLUSION: When compared with CMR a
      continuous overestimation of volumes and underestimation of EF needs to be
      considered when applying MSCT in HFREF patients.

PMID- 19771460
TI  - Gender-specific differences in stroke knowledge, stroke risk perception and the
      effects of an educational multimedia campaign.
AB  - This study aimed at identifying gender-specific differences in stroke knowledge,
      stroke risk perception and the educational effects of a multimodal educational
      intervention. We performed computer-assisted telephone surveys among an average
      sample of 500 members of the general public (44.0% male, 56.0% female), before
      and immediately after an intense 3-month educational stroke campaign in a western
      German area of 400,000 inhabitants. The intervention was comprised of poster
      advertisements and various print media. Slogans and stroke interest stories
      appeared regularly in local newspapers, on television and radio and public events
      focussed on the subject. Even before the intervention, more women than men were
      able to name at least one stroke warning sign (71.3 vs. 57.8%, p < 0.01), to name
      the correct emergency call number (33.3 vs. 24.3%, p < 0.05) or to cite the
      correct action in acute stroke ("call emergency care", 87.2 vs. 70.1%, p <
      0.001). In some aspects women showed a generally better improvement of knowledge
      after the campaign (e.g. correct emergency call number: +5.7 vs. +1.2%, p <
      0.05). Fewer women than men considered themselves as being at risk of stroke
      (30.9 vs. 36.9%. p < 0.01) with a significant increase following the intervention
      in both sexes (38.9/46.0%, p < 0.01). The perception of different educational
      media varied between the sexes. For example, female sex was independently
      associated with a better recall of poster advertisements and flyers in pharmacies
      and at the doctor's office (OR 1.44). Our data indicate that educational programs
      do have gender-specific effects. Women show a better stroke knowledge and in some
      aspects a better chance to gain information from classical broad educational
      interventions. Future campaigns should be tailored economically, and should focus
      different media and educational messages on the two sexes accordingly.

PMID- 19771461
TI  - Assessment of antifouling biocides contaminations in Maizuru Bay, Japan.
AB  - The concentrations of organotin compounds in the aquatic environment of Maizuru
      Bay and their spatial distribution are discussed. The concentrations of
      tributyltin (TBT) compounds in water samples ranged from 0.001 to 0.002 microg l(
      1), and monobutyltin compounds were the dominant species among the butyltin
      compounds. TBT concentrations in Maizuru Bay are low compared with other coastal
      waters of Japan. Drastic differences in TBT concentrations were not observed
      among the Maizuru Bay sites. Phenyltin compounds were not detected in the water
      samples. Concentrations of TBT and triphenyltin (TPT) in sediment from Maizuru
      Bay ranged, respectively, from 0.9 to 11 microg kg(-1), from 0.2 to 17 microg kg(
      1) dry weight (dw). TBT concentrations in Maizuru Bay were lower than those in
      other coastal areas of Japan. TPT concentrations were greater than TBT
      concentrations in the fishing port. The concentrations of TBT and TPT in blue
      mussels (M. galloprovincialis) from Maizuru Bay were in the range of 2.4 to 9.3
      microg kg(-1) and 0.2-13 microg kg(-1) wet weight (ww), respectively. A tolerable
      average residue level (TARL) was estimated at 74.8 microg kg(-1) from a tolerable
      daily intake (TDI) of 0.25 bis(tributyltin)oxide microg kg(-1) body weight day(
      1). TBT concentrations detected in blue mussel samples were lower than the TARL
      values. The acceptable concentration of TPT, which were calculated using
      acceptable daily intake instead of TDI, was 127 microg kg(-1). Concentrations of
      TPT in blue mussel samples were also lower than the TARL. TBT compounds in blue
      mussel samples were at similar levels among the various sampling sites,
      indicating that TBT is not currently being used in ship hull paints; the ratios
      of degradation products of TBT and TPT were greater than those of the parent
      compounds. Concentrations of alternative biocides in water samples were also
      investigated in the bay. Although Sea-Nine 211, M1, and Pyrithiones were not
      detected, Diuron and Irgarol 1051 were detected at 0.010-0.257 and at 0.002-0.018
      microg l(-1), respectively. Concentrations of Diuron were great in the shipping
      route and near the shipyard, whereas the concentration of Irgarol 1051 was great
      at the fishing port. Concentrations of Diuron and Irgarol 1051 in sediment from
      Maizuru Bay ranged, respectively, from <0.08 to 12, from <0.08 to 9.8 microg kg(
      1) dw, respectively. Despite being a semi-enclosed bay, we found that sediment in
      Maizuru Bay is not contaminated by alternative biocides to the degree found in
      other coastal areas. Copper concentrations of sediment were at ordinary levels,
      and those of blue mussels were slightly lower than those reported previously in
      other coastal areas of Japan. In both the sediment and blue mussels, there was no
      correlation between the presence of copper and antifouling biocides.

PMID- 19771462
TI  - Polybrominated diphenyl ethers in outmigrant juvenile Chinook salmon from the
      lower Columbia River and Estuary and Puget Sound, Washington.
AB  - Previous studies have examined the presence, distribution, and concentrations of
      toxic contaminants in two major waterways in the Pacific Northwest: the lower
      Columbia River and Estuary (LCR&E) and Puget Sound, Washington. However, those
      studies have not reported on the levels of polybrominated diphenyl ethers (PBDEs)
      in juvenile Chinook salmon (Onchorynchus tshawytscha). Populations of Chinook
      salmon from the LCR&E and Puget Sound are declining, and some stocks are
      currently listed as "threatened" under the Endangered Species Act.
      Bioaccumulation of contaminants, including PBDEs, by juvenile Chinook salmon in
      the LCR&E and Puget Sound is of concern due to the potential toxicity of the
      contaminants and associated sublethal effects in fish. In this article, we
      present the concentrations of PBDEs measured in gutted bodies and stomach
      contents of outmigrant juvenile Chinook salmon collected at six sites in the
      LCR&E and four sites in Puget Sound. For comparison, we also analyzed gutted
      bodies of juvenile Chinook salmon from eight hatcheries in the LCR&E as well as
      samples of the hatchery fish feeds. The mean summation SigmaPBDE concentrations
      measured in bodies of juvenile Chinook salmon from the different sites ranged
      from 350 to 2800 ng/g lipid weight, whereas those in stomach contents ranged from
      less than the quantitation limit (<2 ng/g wet weight) to 39 ng/g wet weight. The
      levels of PBDEs in the hatchery fish were significantly lower than those measured
      in the salmon samples collected from the LCR&E and Puget Sound. These results
      show that outmigrant juvenile Chinook salmon in the LCR&E and Puget Sound have
      been exposed to PBDEs in the environment and that these chemicals are
      bioaccumulating in their tissues; thus, the potential effects of PBDEs on these
      salmon should be further investigated.

PMID- 19771464
TI  - Pancreatic adenocarcinoma versus chronic pancreatitis: differentiation with
      triple-phase helical CT.
AB  - BACKGROUND: Chronic pancreatitis and pancreatic adenocarcinoma often show similar
      clinical and imaging appearances. This study aims to differentiate chronic
      pancreatitis from pancreatic adenocarcinoma by defining enhancement patterns in
      both pathologic conditions during triple-phase helical CT. METHODS: The study
      included 42 patients with chronic pancreatitis and 85 patients with pancreatic
      adenocarcinoma. CT images obtained according to protocol A (scan delays, 30, 60,
      and 150 s; 300 mg I/mL contrast material) or protocol B (scan delays, 40, 70, and
      150 s; 370 mg I/mL contrast material) were retrospectively evaluated. RESULTS:
      Mean contrast enhancement value of normal pancreas peaked in the first phase
      (early-washout pattern) while that of chronic pancreatitis peaked in the second
      phase (delayed-washout pattern), and that of pancreatic adenocarcinoma gradually
      rose (increasing pattern) in both protocols. Diagnostic indices for pancreatic
      adenocarcinoma were 82.4% and 94.1% for sensitivity, 83% and 83% for specificity,
      82.7% and 90.4% for accuracy in protocols A and B, respectively, when
      differentiation between chronic pancreatitis and pancreatic adenocarcinoma was
      performed based on time-attenuation curve patterns. CONCLUSION: Our results
      indicate that time attenuation curves obtained from triple-phase helical CT in
      protocol B provide useful information in differentiating chronic pancreatitis
      from pancreatic adenocarcinoma.

PMID- 19771463
TI  - Stratification of complexity improves the utility and accuracy of outcomes
      analysis in a Multi-Institutional Congenital Heart Surgery Database: Application
      of the Risk Adjustment in Congenital Heart Surgery (RACHS-1) and Aristotle
      Systems in the Society of Thoracic Surgeons (STS) Congenital Heart Surgery
      Database.
AB  - Quality-of-care evaluation must take into account variations in "ase mix."This
      study reviewed the application of two case-mix complexity-adjustment tools in the
      Society of Thoracic Surgeons (STS) Congenital Heart Surgery Database: the
      Aristotle Basic Complexity (ABC) score and the Risk Adjustment in Congenital
      Heart Surgery (RACHS-1) method. The 2006 STS Congenital Heart Surgery Database
      Report, the first STS report to incorporate both methods, included 45,635
      operations from 47 centers. Each operation was assigned an ABC score in a range
      from 1.5 (lowest complexity) to 15 (highest complexity), an ABC level in a range
      from 1 (lowest complexity) to 4 (highest complexity), and a RACHS-1 category in a
      range from 1 (lowest risk) to 6 (highest risk). The overall discharge mortality
      was 3.9% (1,222/31,719 eligible cardiac index operations). Of the eligible
      cardiac index operations, 85.8% (27,202/31,719) were eligible for analysis by the
      RACHS-1 method, and 94.0% (29,813/31,719) were eligible for analysis by the ABC
      approach. With both RACHS-1 and ABC, as complexity increases, discharge mortality
      also ncreases. The ABC approach allows classification of more operations, whereas
      the RACHS-1 discriminates better at the higher end of complexity. Complexity
      stratification is a useful method for analyzing the impact of case mix on
      pediatric cardiac surgical outcomes. Both the RACHS-1 and ABC methods facilitate
      complexity stratification in the STS database.

PMID- 19771465
TI  - China's primary programs of terrestrial ecosystem restoration: initiation,
      implementation, and challenges.
AB  - China has undertaken several major programs of terrestrial ecosystem restoration
      (ERPs) in recent years, including the Natural Forest Protection Program (NFPP)
      and the Sloping Land Conversion Program (SLCP). There have been reports on the
      implementation of these programs, their preliminary impacts, and the problems
      encountered in carrying them out; a great deal has been learned from these
      studies. Nonetheless, China's ERPs are not limited to the NFPP and the SLCP.
      Because a complete documentation and a timely update of these major efforts are
      still missing from the literature, it is difficult to gauge the scope of these
      programs and the scale of their impacts. In addition, a more thorough and
      critical analysis of both the general ERP policy and the specific technical
      measures used in implementing the ERPs remains urgently needed. The purpose of
      this article is to tackle these tasks. Overall, with the huge government
      investments in the ERPs, tremendous progress has been made in implementing them.
      To complete them successfully and to fundamentally improve the targeted
      ecosystems, however, it is essential for China to have a more balanced and
      comprehensive approach to ecological restoration. This approach must include:
      adopting better planning and management practices; strengthening the governance
      of program implementation; emphasizing the active engagement of local people;
      establishing an independent, competent monitoring network; and conducting
      adequate assessments of program effectiveness and impact.

PMID- 19771466
TI  - Comparative cost-effectiveness analysis of two MSF surgical trauma centers.
AB  - INTRODUCTION: There is a dearth of data on cost-effectiveness of surgical care in
      resource-poor countries. Doctors Without Borders (Medecins Sans Frontieres; MSF)
      is a nongovernmental organization (NGO) involved in the many facets of health
      care for underserved populations, including surgical care. METHODS: A cost
      effectiveness analysis (CEA) was attempted at two of their surgical trauma
      hospitals: Teme Hospital in Nigeria and La Trinite Hospital in Haiti. CONCLUSION:
      At $172 and $223 per Disability-Adjusted Life-Year (DALY) averted, respectively,
      they are in line with other reported CEAs for surgical and nonsurgical activities
      in similar contexts.

PMID- 19771467
TI  - Chronic schistosomiasis japonica is an independent adverse prognostic factor for
      survival in hepatocellular carcinoma patients who have undergone hepatic
      resection: clinicopathological and prognostic analysis of 198 consecutive
      patients.
AB  - BACKGROUND: The present study was carried out to clarify the clinicopathological
      features of hepatocellular carcinoma (HCC) patients with chronic schistosomiasis
      japonica (SJ) who underwent hepatic resection. Furthermore, we also analyzed the
      impact of chronic SJ on survival after hepatic resection. METHODS: During the
      last 10 years in our department, 198 patients have undergone hepatic resection
      for HCC. Forty-four patients were diagnosed as having chronic SJ by histological
      examination. Clinicopathological features and survival were retrospectively
      analyzed. RESULTS: Age in the SJ group was significantly higher than in the non
      SJ group. In the SJ group, positivity to HBsAg (hepatitis B surface antigen) was
      significantly lower than in the non-SJ group, and patients more often developed
      intrahepatic cholangiocellular carcinoma (or cholangiolocellular carcinoma) than
      in the non-SJ group. Greatest tumor dimension in the SJ group was significantly
      larger than in the non-SJ group. Univariate analysis revealed that chronic SJ,
      prothrombin time 80% or less and Child-Pugh B, des-gamma-carboxyprothrombin (DCP)
      level >40 milli-arbitrary units (mAU)/ml, tumor diameter of more than 5.0 cm,
      multiple tumors, vascular invasion, intrahepatic metastasis, advanced T stage (T2
      4), and non-curative resection were associated with significantly worse overall
      survival. By multivariate analysis, chronic SJ, Child-Pugh B, advanced T stage,
      and non-curative resection were independent predictors of the adverse overall
      survival of HCC patients after hepatic resection. CONCLUSIONS: Patients with
      chronic SJ were older, had larger HCC, and were more often complicated by
      cholangiocellular carcinoma (or cholangiolocellular carcinoma) than non-SJ
      patients. Chronic SJ was an independent adverse prognostic factor for survival
      after hepatic resection in HCC patients.

PMID- 19771468
TI  - A phase I study of intraoperative radiotherapy for early breast cancer in Japan.
AB  - BACKGROUND: The present study was designed to identify the optimal intraoperative
      radiotherapy (IORT) dose for early breast cancer in Japanese women. METHODS: A
      phase I study was designed using a scheme of dose-escalation from 19, 20, and 21
      Gy at 90% isodose. The primary endpoint was early toxicity. Secondary endpoints
      were efficacy for a long period and late toxicity. Inclusion criteria were as
      follows: (1) tumor size <2.5 cm, (2) age >50 years, (3) surgical margin >1 cm,
      (4) intraoperative pathologically free margins, (5) written informed consent.
      Exclusion criteria were (1) contraindication to radiation therapy, (2) extensive
      intraductal component. Partial resection was performed with at least a 1-cm
      margin around the tumor. Radiation was delivered directly to the mammary gland
      employing a MOBETRON device. Toxicity was evaluated with the Common Terminology
      Criteria for Adverse Events (CTCAE), version 3.0. RESULTS: From December 2007 to
      September 2008, 9 patients were enrolled in the study. The first three patients
      received a radiation dose of 19 Gy. Within 3 months toxicity in each case was
      deep connective tissue fibrosis (grade 1: 2/3, grade 2: 1/3). The next three
      patients received a dose of 20 Gy and had toxicities of deep connective tissue
      fibrosis (grade 1: 3/3), hematoma (grade 1: 2/3), infection in the
      musculoskeletal soft tissue (grade 1: 2/3), and soft tissue necrosis (grade 2:
      1/3). The final three patients received a dose of 21 Gy and had toxicities of
      deep connective tissue fibrosis (grade 1: 2/3), hematoma (grade 1: 1/3),
      infection in the musculoskeletal soft tissue (grade 1: 1/3), and soft tissue
      necrosis (grade 2: 2/3). CONCLUSIONS: The IORT treatment was tolerated very well
      in Japanese women, and we now recommend the dose of 21 Gy.

PMID- 19771469
TI  - Retromammary approach for endoscopic resection of benign breast lesions.
AB  - BACKGROUND: One of the merits of endoscopic surgery is that it can be performed
      through small remote incisions made in inconspicuous areas. To improve cosmetic
      outcomes of surgical treatment of benign breast lesions, we performed endoscopic
      surgery through minimally sized axillary incisions with the goal of achieving
      scar-free breasts. METHODS: From August 2007 to August 2008, 18 patients with 20
      benign breast lesions underwent endoscopic breast excision in our institution.
      Endoscopic resection of benign breast lesions was performed via the retromammary
      route with video assistance. Cosmetic results were evaluated using the five-item,
      four-step ABNSW scoring system, assessing breast asymmetry, breast shape, nipple
      shape, skin condition, and wound scars. RESULTS: The median age of the patients
      was 27 years (IQR 23.0, 29.0). Median resected lesion size was 3.3 cm (IQR 2.9,
      3.9). Median operative time was 85.0 min (IQR 70.0, 100.0). A marginally
      significant difference in operative times was noted between fibroadenoma and/or
      juvenile fibroadenoma cases and mastopathy or benign phyllodes cases (80.0 vs.
      100.0; p < 0.06). Median total ABNSW score was 14 points. Postoperatively, 5
      patients had mild local subcutaneous emphysema, and one had transient brachial
      palsy. No breast ecchymosis or deformity was noted. No major complications
      developed in any patient, and 89% of patients had good or excellent results.
      CONCLUSIONS: Video-assisted endoscopic breast surgery has changed routine breast
      surgery, manifesting cosmetic effects that cannot be achieved by previous routine
      surgical techniques. Patients with multiple or large benign tumors who desire
      excellent cosmetic results are good candidates for this approach.

PMID- 19771471
TI  - Experience with reversed L-shaped incision for right hemicolectomy combined with
      liver resection.
AB  - BACKGROUND: Various types of incisions have been applied in simultaneous
      resections of colorectal cancer and synchronous liver metastases. We describe our
      experience with the reversed L-shaped incision for simultaneous right
      hemicolectomy and liver resection. METHODS: We applied the reversed L-shaped
      incision in nine patients who underwent simultaneous right hemicolectomy and
      right liver resection or left hepatectomy. A reversed L-shaped incision of the
      abdomen was consisted of midline and transverse incisions with the junction of
      the umbilicus. The operative field was kept open using Kent retractors. First,
      right colon mobilization was performed easily and right hemicolectomy was
      performed. Subsequently, liver mobilization with identification of hepatic
      vessels was achieved and right liver resection or left hepatectomy was performed.
      RESULTS: The reversed L-shaped incision successfully provided a good and rapid
      exposure in nine patients. There were no complications, such as wound infection,
      lung atelectasis/pneumonia, or incisional hernia, in patients with the reversed L
      shaped incision. CONCLUSIONS: Our preliminary experience demonstrated that the
      reversed L-shaped incision might be a good choice in a subset of patients with
      simultaneous right hemicolectomy and right liver resection or left hepatectomy.
      However, a large, prospective, controlled study comparing different incision
      types in the same procedure with variables, such as operating time, postoperative
      pain scores, patient's satisfaction, and postoperative complication, is needed to
      support the benefit of the reversed L-shaped incision.

PMID- 19771470
TI  - Impact of gender and age on the long-term outcome of laparoscopic fundoplication.
AB  - BACKGROUND: It has been suggested that gender and age could be factors that
      influence the likelihood of success following antireflux surgery, and our
      anecdotal impression has been that the outcome following Nissen fundoplication in
      older women is often disappointing. If correct, characterization of the extent of
      any differences in outcome might help patient selection and, hence, surgical
      outcomes. Therefore, in this study we investigated the impact of gender and age
      on longer-term clinical outcomes following laparoscopic fundoplication. METHODS:
      Perioperative and follow-up data from patients undergoing laparoscopic
      fundoplication in our departments have been collected prospectively and stored in
      a database. From the database, patients who had undergone either an anterior 180
      degrees partial or 360 degrees total laparoscopic fundoplication for
      gastroesophageal reflux and completed 5 years clinical follow-up were identified.
      Patients were classified according to gender and age, and outcome data were
      analyzed to determine differences. Analog scales of 0-10 were used to determine
      symptoms of heartburn and dysphagia and overall satisfaction. RESULTS: Seven
      hundred three patients were studied (58% males). Females were less satisfied with
      the outcome (score = 7.8 +/- 2.8 vs. 8.4 +/- 2.5, P = 0.0036), and had higher
      scores for heartburn (2.0 +/- 2.7 vs. 1.2 +/- 2.2; P = 0.0001) and dysphagia for
      solid food (2.7 +/- 2.9 vs. 2.0 +/- 2.5, P = 0.0049) compared to males.
      Revisional procedures were undertaken more frequently in females (15.5% vs. 8.4%,
      P = 0.0038). Age had no impact on any clinical outcome. CONCLUSIONS: While the
      outcome for laparoscopic fundoplication is not influenced by age, the outcome for
      women is poorer than in males.

PMID- 19771472
TI  - Use of botulinum toxin type a before abdominal wall hernia reconstruction.
AB  - BACKGROUND: Abdominal wall hernia repair after open abdomen management represents
      a surgical challenge, particularly due to muscle tension and lateral retraction.
      This study was designed to propose the use of Botulinum Toxin Type A (BTA) before
      abdominal wall hernia repair. METHODS: A prospective study of patients with
      abdominal wall hernia after open abdomen management was undertaken between
      September 2007 and January 2009. Bilateral BTA application was performed under
      electromyographic guidance at the abdominal wall. Transverse abdominal wall
      defect measurement was practiced at weekly intervals: clinically, in the first
      two patients, and with CT scan in the following 10 patients. Surgical closure was
      scheduled if no further hernia defect reduction was noted. Patients were followed
      at monthly hospital visits. RESULTS: In the first two patients, a hernia defect
      reduction of 50 and 47.2%, respectively, was documented by the third week after
      BTA application, with no further reduction. In the 10 patients under CT scan
      hernia defect measurement, when comparing the initial mean transverse defect
      measure and at 4 weeks after BTA application (13.85 +/- 1.49 cm vs. 8.6 +/- 2.07
      cm), an overall mean reduction of 5.25 +/- 2.32 cm was observed (p < 0.001; 95%
      confidence interval, 3.59-6.91). Hernia repair was performed, with no recurrences
      at a mean follow-up of 9.08 months. CONCLUSIONS: BTA application before abdominal
      wall hernia repair seems to be useful. The lateral muscles paralysis achieved and
      transverse hernia defect reduction allows a minimal tension closure. To our
      knowledge, this is the first report of BTA application before abdominal wall
      hernia reconstruction.

PMID- 19771473
TI  - Quantification of left ventricular parameters obtained by automated software for
      64-slice multidetector computed tomography and comparison with magnetic resonance
      imaging.
AB  - The dataset obtained with 64-slice multidetector CT (MDCT) for coronary artery
      evaluation can be used to calculate important left ventricular (LV) volumetric
      parameters. We compared LV parameters derived by new, commercially available,
      fully automated software for MDCT (Syngo Circulation, Siemens, Germany) to
      cardiac magnetic resonance (CMR) as a reference standard. Twenty patients
      underwent CMR after completing a clinically indicated MDCT. Ejection fraction
      (EF), end-systolic volume (ESV), end-diastolic volume (EDV), stroke volume (SV),
      and myocardial mass (MM) for MDCT were obtained using automated software and were
      compared to CMR measurements, with papillary muscles (PMs) included in, or
      excluded from, the blood pool. The Pearson correlation coefficient (r) and Bland
      Altman method were used to determine agreement between methods. When PMs were
      included in the blood pool, the correlation was excellent for EF (r=0.92,
      p?0.001), ESV (r=0.86, p?0.001), and EDV (r=0.80, p?0.001). When PMs were
      excluded from CMR, correlation was still very good for EF (r=0.89, p?0.001), ESV
      (r=0.82, p?0.001), and EDV (r=0.82, p?0.001). MDCT values for SV and MM showed a
      good correlation compared to both CMR methods. When PMs were included, the
      correlation was good for SV (r=0.70, p?0.001), and MM (r=0.70, p?0.001); when
      they were excluded, the correlation was less robust but still significant for SV
      (r=0.71, p?0.001) and MM (r=0.73, p?0.001). In conclusion, EF, ESV, and EDV
      obtained by MDCT using simple, automated software correlated very well with CMR;
      SV and MM showed good correlation. Automated analysis of volumetric parameters by
      MDCT can be reliably utilized for clinical purposes.

PMID- 19771474
TI  - Central vein dilatation prior to concomitant port implantation.
AB  - Implantation of subcutaneous port systems is routinely performed in patients
      requiring repeated long-term infusion therapy. Ultrasound- and fluoroscopy-guided
      implantation under local anesthesia is broadly established in interventional
      radiology and has decreased the rate of complications compared to the surgical
      approach. In addition, interventional radiology offers the unique possibility of
      simultaneous management of venous occlusion. We present a technique for
      recanalization of central venous occlusion and angioplasty combined with port
      placement in a single intervention which we performed in two patients. Surgical
      port placement was impossible owing to occlusion of the superior vena cava
      following placement of a cardiac pacemaker and occlusion of multiple central
      veins due to paraneoplastic coagulopathy, respectively. In both cases the
      affected vessel segments were dilated with balloon catheters and the port systems
      were placed thereafter. After successful dilatation, the venous access was
      secured with a 25-cm-long, 8-Fr introducer sheath, a subcutaneous pocket
      prepared, and the port catheter tunneled to the venipuncture site. The port
      catheter was introduced through the sheath with the proximal end connected to a 5
      Fr catheter. This catheter was pulled through the tunnel in order to preserve the
      tunnel and, at the same time, allow safe removal of the long sheath over the
      wire. The port system functioned well in both cases. The combination of
      recanalization and port placement in a single intervention is a straightforward
      alternative for patients with central venous occlusion that can only be offered
      by interventional radiology.

PMID- 19771475
TI  - Pseudomonas benzenivorans sp. nov. and Pseudomonas saponiphila sp. nov.,
      represented by xenobiotics degrading type strains.
AB  - Two strains of gram-negative bacteria isolated because of their abilities to
      decompose xenobiotic compounds were subjected to a polyphasic taxonomic study. On
      the basis of 16S rRNA gene sequence analysis, the two strains were found to
      belong to the genus Pseudomonas. Benzene degrading strain DSM 8628(T) was
      moderately related to P. flavescens NCPP 3063(T) (98.3% similarity), P. monteilii
      CIP 104883(T), and P. plecoglossicida FPC 951(T) (98.1%). Strain DSM 9751(T)
      capable to grow with cetyltrimethylammonium chloride as the sole carbon source
      showed the highest similarity values with P. tremae CFBP 2341(T) and P. meliae
      MAFF 301463(T) (98.0%), both related to Pseudomonas syringae. The fatty acid
      pattern of strain DSM 8628(T) was distinct from patterns of other members of the
      genus Pseudomonas in combining a high ratio of 3OH-C(12:1) (5.1%), a low ratio of
      2OH-C(12:0) (0.2%) and a relatively low ratio of C(18:1)omega7c (23.8%). On the
      basis of phylogenetic analysis, physiological properties and the composition of
      whole cell fatty acids, two novel species, Pseudomonas benzenivorans sp. nov.
      with the type strain DSM 8628(T) (=CIP 109857(T)) and Pseudomonas saponiphila sp.
      nov. with the type strain DSM 9751(T) (=CIP 109856(T)), are proposed.

PMID- 19771476
TI  - Purified capsular polysaccharide of Neisseria meningitidis serogroup A as immune
      potentiator for antibody production.
AB  - The development of new immune potentiators for human vaccines is an important and
      expanding field of research. In the present study, the ability of the capsular
      polysaccharide from Neisseria meningitidis serogroup A (CPS-A), a mannose
      containing carbohydrate, to enhance the antibody production against a co
      administered model vaccine antigen, is examined. A protein-meningococcal
      serogroup C capsular polysaccharide (CPS-C) conjugate was selected as the model
      antigen for this study. After subcutaneous immunization of Balb/C mice, the
      conjugate mixed with CPS-A induced higher anti-CPS-C IgG and IgG(2a) antibody
      levels and higher anti-meningococcal serogroup C bactericidal titers than the
      conjugate alone or mixed with CPS-C. The immuno-stimulatory properties exhibited
      by CPS-A and the fact that vaccines based on purified CPS-A has been safely used
      during decades to fight the serogroup A meningococcal disease, support the
      proposal to use CPS-A as immune potentiator for human vaccination studies.

PMID- 19771477
TI  - RNase 1 genes from the family Sciuridae define a novel rodent ribonuclease
      cluster.
AB  - The RNase A ribonucleases are a complex group of functionally diverse secretory
      proteins with conserved enzymatic activity. We have identified novel RNase 1
      genes from four species of squirrel (order Rodentia, family Sciuridae). Squirrel
      RNase 1 genes encode typical RNase A ribonucleases, each with eight cysteines, a
      conserved CKXXNTF signature motif, and a canonical His(12)-Lys(41)-His(119)
      catalytic triad. Two alleles encode Callosciurus prevostii RNase 1, which include
      a Ser(18)<-->Pro, analogous to the sequence polymorphisms found among the RNase 1
      duplications in the genome of Rattus exulans. Interestingly, although the
      squirrel RNase 1 genes are closely related to one another (77-95% amino acid
      sequence identity), the cluster as a whole is distinct and divergent from the
      clusters including RNase 1 genes from other rodent species. We examined the
      specific sites at which Sciuridae RNase 1s diverge from Muridae/Cricetidae RNase
      1s and determined that the divergent sites are located on the external surface,
      with complete sparing of the catalytic crevice. The full significance of these
      findings awaits a more complete understanding of biological role of mammalian
      RNase 1s.

PMID- 19771478
TI  - Lack of association between asthma and ABO blood group.
AB  - ABO is the most important blood group system in transfusion and transplantation
      practices. Glycosyltransferases are controlled by the ABO system which is helpful
      in building oligosaccharide structures on the cell surface of erythrocytes and
      vascular endothelium and in the exocrine secretion system, including the
      respiratory tract. We analyzed the ABO blood group of 200 children and adults
      with asthma as well as that of 2000 healthy subjects as controls. The most common
      blood group among the patients and controls was "O" (43.5% and 43.6%,
      respectively), followed by B, A, and AB. In the distribution of different blood
      groups, nonsignificant difference between patients and controls was observed (p =
      0.931). We conclude that ABO blood group status has a nonsignificant association
      with asthma among the population of Mysore, Karnataka, South India.

PMID- 19771479
TI  - Conversion of glenohumeral fusion to total shoulder arthroplasty for
      scapulothoracic pain: case report and surgical technique.
AB  - There are several references in the hip and knee literature that mention
      converting fusions to a prosthetic total arthroplasty, but similar reports of
      total shoulder arthroplasty after glenohumeral fusion are lacking. The indication
      for conversion of a glenohumeral arthrodesis to a total shoulder arthroplasty is
      persistent periscapular pain refractory to conservative treatment. The purpose of
      the following article is to describe the preoperative plan and surgical technique
      in the conversion of a glenohumeral fusion to a total shoulder arthroplasty in
      single case of protracted scapulothoracic pain.

PMID- 19771480
TI  - Theoretical considerations of Fisher's theorem in small at-risk populations.
AB  - Small populations at risk of extinction due to threshold or competitive exclusion
      have a vested interest in rapid growth. Taking chance of survival into account
      for diploid populations, Fisher's theorem predicts a sex ratio favoring females
      under certain circumstances. Theoretical consideration of competitive exclusion
      shows such circumstances are reasonable under accepted modeling assumptions.

PMID- 19771481
TI  - Nonverbal sensitivity in medical students: implications for clinical
      interactions.
AB  - BACKGROUND: Clinicians' accuracy in perceiving nonverbal cues has potentially
      important consequences, but has received insufficient research. OBJECTIVE: To
      examine the relation of medical students' nonverbal sensitivity to their gender
      and personal traits, as well as to their communication and impressions made
      during a standardized patient (SP) visit. DESIGN: Psychometric testing,
      questionnaire, and observation. SETTING: One US medical school. PARTICIPANTS: Two
      hundred seventy-five third-year medical students. MEASUREMENTS: Nonverbal
      sensitivity and attitudes were measured using standard instruments. Communication
      during the SP visit was measured using trained coders and analogue patients who
      viewed the videotapes and rated the favorability of their impressions of the
      student. RESULTS: Nonverbal sensitivity was higher in female than male students
      (P < 0.001) and was positively correlated with self-reported patient-centered
      attitudes (P < 0.01) and ability to name one's own emotions (P < 0.05). It was
      also associated with less distressed (P < 0.05), more dominant (P < 0.001), and
      more engaged (P < 0.01) behavior by the SP, and with more liking of the medical
      student (P < 0.05) and higher ratings of compassion (P < 0.05) by the analogue
      patients. Correlations between nonverbal sensitivity and other variables were
      generally stronger and different for male than female students, but nonverbal
      sensitivity predicted analogue patients' impressions similarly for male and
      female students. CONCLUSION: Medical students' nonverbal sensitivity was related
      to clinically relevant attitudes and behavioral style in a clinical simulation.

PMID- 19771482
TI  - Use of aspirin among diabetics in the primary prevention of cardiovascular
      disease: need for reliable randomized evidence and astute clinical judgment.
AB  - BACKGROUND: The American Heart Association Guidelines recommend aspirin for all
      apparently healthy individuals whose 10-year risk of a first coronary heart
      disease (CHD) event is >10%. METHODS: The United States (US) Preventive Services
      Task Force (USPSTF) has recently updated its guidelines to encourage men 45 to 79
      years and women 55 to 79 years to use aspirin when the potential benefit
      outweighs the potential harm. In addition, in some US guidelines, diabetes is
      considered to be a CHD risk equivalent. RESULTS: Two recently published trials,
      the Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes
      (JPAD) and the Prevention of Progression of Arterial Disease and Diabetes
      (POPADAD), concluded that aspirin did not reduce risks of CHD. Both JPAD and
      POPADAD had inadequate statistical power. Reliable randomized evidence is
      necessary to provide a sufficient totality of evidence about benefits and risks
      among diabetics. CONCLUSION: At present, astute individual clinical judgments are
      necessary.

PMID- 19771483
TI  - CME post test.

PMID- 19771484
TI  - CME information.

PMID- 19771485
TI  - Incidence of 'squeaking' after ceramic-on-ceramic total hip arthroplasty.
AB  - The incidence of hip "squeak" associated with ceramic-on-ceramic bearings has
      been variably reported, ranging from 0.7% to 20.9%. We determined the patients'
      perception of squeaking in 306 patients (336 hips) in whom ceramic-on-ceramic
      total hip arthroplasties (THAs) were performed between 1997 and 2005. A
      questionnaire regarding hip noise was obtained by telephone. With a minimum
      followup of 2 years (mean, 3.9 years; range, 2-10 years), 290 patients (320 or
      95% of the THAs) completed the questionnaire. Patients reported hip noise in 55
      of the 320 THAs (17%); noise was perceived as squeak in 32 of the 320 (10%). Most
      squeaking hips (29 of 32) were pain-free and symptom-free. One patient was
      unhappy with his squeaking hip without pain. Our data suggest a much higher
      incidence of squeak as perceived by patients than previously reported. LEVEL OF
      EVIDENCE: Level II, therapeutic study. See Guidelines for Authors for a complete
      description of levels of evidence.

PMID- 19771486
TI  - The role of integrin alpha(v)beta (8) in neonatal hypoxic-ischemic brain injury.
AB  - Integrin alpha(v)beta(8) plays an important role in cerebral vascular
      development. It has been proven that alpha(v)beta(8) is a key factor for
      transforming growth factor-beta1 (TGF-beta1) activation in epithelial cells.
      However, it is not clear whether alpha(v)beta(8) can activate TGF-beta1 and play
      a role in protection during neonatal hypoxic-ischemic brain injury. In this
      study, we investigated the relationship between alpha(v)beta(8) and TGF-beta1
      activation, and thus the effects of TGF-beta1 activation in the protection of
      neurons after hypoxia-ischemia (HI). Astrocytes and neurons from rat brains were
      cultured and then subjected to oxygen-glucose deprivation to generate HI model in
      vitro. beta(8) expression was determined using immunocytochemistry, western blot,
      and reverse-transcriptase polymerase chain reaction. TGF-beta1 activation was
      determined by TGF-beta bioassay in a tested cell (astrocyte) and a reporter cell
      co-culture system. The pro-apoptotic protein, cleaved caspase-3, and the anti
      apoptotic protein, Bcl-2 and Bcl-xL, were detected using western blot. Cellular
      apoptosis was detected with TUNEL. We found that beta(8) expression was stronger
      in astrocytes than that in neurons under normoxia. HI resulted in a rapid and
      persistent increase of beta(8) expression in astrocytes, but only in a slight and
      transient increase in neurons. Astrocytes beta(8) could induce TGF-beta1 leading
      to upregulation of Bcl-2 and Bcl-xL, and thus attenuated neuronal apoptosis. The
      present findings suggest that beta(8) protecting the brain against neonatal HI
      injury through TGF-beta1 signaling pathway, which may have implications for the
      treatment of HI brain injury.

PMID- 19771487
TI  - Prior nonhip limb fracture predicts subsequent hip fracture in institutionalized
      elderly people.
AB  - SUMMARY: This 1-year cohort study of nursing home residents revealed that
      historical fractures of upper limbs or nonhip lower limbs were associated with
      hip fracture (hazard ratio = 2.14), independent of activities of daily living
      (ADL), mobility, dementia, weight, and type of nursing home. Prior nonhip
      fractures are useful for predicting of hip fracture in institutional settings.
      INTRODUCTION: The aim of this study was to evaluate the utility of fracture
      history for the prediction of hip fracture in nursing home residents. METHODS:
      This was a cohort study with a 1-year follow-up. Subjects were 8,905 residents of
      nursing homes in Niigata, Japan (mean age, 84.3 years). Fracture histories were
      obtained from nursing home medical records. ADL levels were assessed by
      caregivers. Hip fracture diagnosis was based on hospital medical records.
      RESULTS: Subjects had fracture histories of upper limbs (5.0%), hip (14.0%), and
      nonhip lower limbs (4.6%). Among historical single fractures, only prior nonhip
      lower limbs significantly predicted subsequent fracture (adjusted hazard ratio,
      2.43; 95% confidence interval (CI), 1.30-4.57). The stepwise method selected the
      best model, in which a combined historical fracture at upper limbs or nonhip
      lower limbs (adjusted hazard ratio, 2.14; 95% CI, 1.30-3.52), dependence, ADL
      levels, mobility, dementia, weight, and type of nursing home independently
      predicted subsequent hip fracture. CONCLUSIONS: A fracture history at upper or
      nonhip lower limbs, in combination with other known risk factors, is useful for
      the prediction of future hip fracture in institutional settings.

PMID- 19771488
TI  - Micro-CT and mechanical evaluation of subchondral trabecular bone structure
      between postmenopausal women with osteoarthritis and osteoporosis.
AB  - SUMMARY: An inverse relationship between osteoarthritis and osteoporosis has been
      debated over years. The microstructure of the femoral heads from postmenopausal
      osteoarthritic and osteoporotic women was evaluated with micro-CT. Significant
      differences were observed in microstructural parameters between them. Different
      microstructure might relate to the opposite bone defects in osteoarthritis and
      osteoporosis. INTRODUCTION: This study was undertaken to verify the inverse
      relationship between osteoarthritis (OA) and osteoporosis (OP) by comparing the
      structural and mechanical indices. METHODS: Femoral head specimens were obtained
      from 17 postmenopausal women (OA, n = 8; OP, n = 9) during hip surgery. The
      microstructural parameters were measured with micro-CT. Mechanical test was
      performed after bone cube scanning. RESULTS: Significant difference in bone
      volume fraction (BV/TV) and trabecular thickness was noted between OA and OP
      groups. Structure model index decreased in OA, and increased in OP. The higher
      apparent density (AD) and lower material density (MD) were also shown in OA.
      Different from OP, positive correlation were noted between connectivity density
      and mechanical indices in OA. In OA group, BV/TV was associated with Young's
      modulus and AD, while trabecular number was the only parameter that correlated
      with MD. However, in OP group, only BV/TV correlated with yield strength, AD, and
      MD. CONCLUSIONS: We observed the difference in microstructure between
      postmenopausal women with OA and OP, which might relate to the opposite bone
      defects in OA and OP. BV/TV might play an important role in mechanical properties
      of the subchondral bone in either OA or OP.

PMID- 19771490
TI  - Palindromic rheumatism: a descriptive report of seven cases from North Dakota and
      a short review of literature.
AB  - The population of North Dakota is predominantly of Scandinavian (Norwegian) or
      German descent. We analyzed a cohort of all patients diagnosed with palindromic
      rheumatism (PR) and followed-up (by the investigator PK) at the St. Alexius
      Medical Center, Specialty Clinics, Bismarck, North Dakota, from August 16, 2006
      to September 16, 2008. Standard statistical methodology was used to analyze the
      data. The proportion of patients with PR out of the total number of patients with
      rheumatoid arthritis (RA) seen during the timeframe of this study at our
      institution was 0.9%. The demographics, clinical features, and response to
      treatment of our patient-population with PR were quite similar to what has been
      described in the literature. However, we did not observe an evolution of PR into
      rheumatoid arthritis or any other "identifiable" inflammatory arthropathy
      although the follow-up was done very regularly (at least every 3 months), the
      average duration of follow-up being 12.1 months. Also, testing for the HLA B27
      allele was positive in 3 (42.86%) patients, much higher than the "background"
      prevalence of this gene. This small, longitudinal study describes the
      epidemiology, clinical features, laboratory and radiographic findings, and course
      of PR in a small but closed community. This is the first descriptive report of PR
      to the best of our knowledge from the unique state of North Dakota.

PMID- 19771489
TI  - Independent from muscle power and balance performance, a creatinine clearance
      below 65 ml/min is a significant and independent risk factor for falls and fall
      related fractures in elderly men and women diagnosed with osteoporosis.
AB  - We assessed in a cross-sectional study in elderly men and women with
      osteoporosis, the association between the creatinine clearance (CrCl) and the
      performance in different balance and muscle power and function tests and found
      that a decreasing creatinine clearance was significantly associated with lower
      balance and muscle power. INTRODUCTION: To determine if a creatinine clearance of
      <65 ml/min is significantly associated with decreasing muscle power and balance
      and an increased risk for falls and fractures. METHODS: We assessed in a cross
      sectional-study in 1781 German osteoporotic patients, the association between the
      CrCl, the physical performance, and the number of falls and fractures. RESULTS:
      Controlling for age, gender, BMI, and osteoporosis treatment (fracture analysis
      only), a decreasing CrCl was associated with lower physical performance in the
      timed-up-and-go test (corr -0.2337, P < 0.0001), chair-rising test (corr -0.1706,
      P < 0.001), and tandem-stand test (corr 0.2193, P < 0.0001), and a CrCl of <65
      ml/min was associated with a significantly higher risk for falls (47.7% vs.
      36.2%, P = 0.0008) and fall-related fractures (33.1% vs. 22.9%, P = 0.0003)
      compared with a CrCl of >or=65 ml/min. CONCLUSIONS: In this study, we found a
      significant gender-independent correlation between decreasing CrCl and lower
      performance in balance and muscle power tests. Reduced muscle power and balance
      may therefore be involved in the low creatinine clearance associated increased
      risk for falls and fall-related fractures. Furthermore, we found that a CrCl <65
      ml/min., independent from the performance in muscle power, muscle function, and
      balance tests, is a significant risk factor for falls and fractures.

PMID- 19771492
TI  - Urocortin 1 administered into the hypothalamic supraoptic nucleus affects open
      field behaviour in rats.
AB  - The presence of both Urocortin 1 (Ucn1) and corticotropin-releasing factor 2
      receptors (CRF(2)R) in the hypothalamic supraoptic nucleus (SON) suggests that
      endogenous Ucn1 released within this brain area acts as a local signal that might
      be involved in the regulation of not only endocrine but also behavioural stress
      responses. To test this hypothesis, we monitored the effects induced by the
      administration of a range of doses of synthetic Ucn1 (0.001-1.0 microg)
      bilaterally into the SON of rats in the open field test (OFT). Ucn1
      administration produced an inverted U-shaped dose-response curve on OFT
      behaviour, in particular the dose of 0.01 microg of Ucn1 significantly increased
      the number of rearing and grooming episodes without affecting locomotion. In
      addition, this dosage augmented also the latency to visit the centre of the open
      field. Pre-treatment with the CRF(2)R antagonist, astressin-2B (0.1 microg)
      normalized Ucn1 treatment-induced effects. These results suggest that Ucn1
      released within the SON area interacts with CRF(2)R to control the state of
      arousal.

PMID- 19771491
TI  - A meta-analysis of the efficacy and safety of using infliximab for the treatment
      of rheumatoid arthritis.
AB  - Infliximab is a chimeric monoclonal antibody. Published studies indicate that its
      use in patients with rheumatoid arthritis can be efficient in providing long-term
      benefits. The aim of this study is to evaluate the efficacy and safety of using
      infliximab for the treatment of rheumatoid arthritis. A systematic review was
      performed to search for randomized clinical trials that compared intravenous
      administration of 3 mg/kg body weight infliximab or placebo in patients
      concomitantly using methotrexate. Only studies of moderate or high quality were
      included. A meta-analysis was conducted to assess the efficacy (based on changes
      of American College of Rheumatology (ACR) criteria) and the safety (based on
      serious adverse events, serious infections, malignancy, and deaths) of infliximab
      use. Withdrawals due to adverse events or lack of efficacy were also evaluated in
      both infliximab-treated and control groups. Seven trials met the inclusion
      criteria, comprising 2,129 patients. In the efficacy meta-analysis, a greater
      number of infliximab-treated patients relative to those in the placebo group
      achieved ACR20, ACR50, and ACR70 values from 14 weeks to 2 years of treatment.
      For safety analysis, there were no statistically significant differences between
      the groups. Withdrawals due to adverse events were higher in the infliximab group
      relative to the placebo group, and withdrawals due to lack of efficacy were
      higher in the placebo group relative to the infliximab-treated group. This meta
      analysis shows a higher efficacy of infliximab relative to placebo without
      significant safety differences between the infliximab-treated and control groups.

PMID- 19771493
TI  - Bone regeneration potential of a soybean-based filler: experimental study in a
      rabbit cancellous bone defects.
AB  - Autologous and allogenic bone grafts are considered as materials of choice for
      bone reconstructive surgery, but limited availability, risks of transmittable
      diseases and inconsistent clinical performances have prompted the development of
      alternative biomaterials. The present work compares the bone regeneration
      potential of a soybean based bone filler (SB bone filler) in comparison to a
      commercial 50:50 poly(D: ,L: lactide-glycolide)-based bone graft (Fisiograft((R))
      gel) when implanted into a critical size defect (6-mm diameter, 10-mm length) in
      rabbit distal femurs. The histomorphometric and microhardness analyses of femoral
      condyles 4, 8, 16 and 24 weeks after surgery showed that no significant
      difference was found in the percentage of both bone repair and bone in-growth in
      the external, medium and inner defect areas. The SB filler-treated defects showed
      significantly higher outer bone formation and microhardness results at 24 weeks
      than Fisiograft((R)) gel (P < 0.05). Soybean-based biomaterials clearly promoted
      bone repair through a mechanism of action that is likely to involve both the
      scaffolding role of the biomaterial for osteoblasts and the induction of their
      differentiation.

PMID- 19771494
TI  - Synthesis of mesoporous structured hydroxyapatite particles  using yeast cells as
      the template.
AB  - In this study, hydroxyapatite (HAp) particles with mesoporous structure have been
      synthesized from calcium hydroxide and di-ammonium hydrogen phosphate using yeast
      cells as the template. The characterization methods such as X-ray diffraction
      (XRD), Fourier transform infrared spectrograph (FTIR), N(2) adsorption-desorption
      isotherms (NADI), transmission electron microscopy (TEM) and field emission
      scanning electron microscopy (FESEM) were used for determination of the particles
      structure (particle size, structural evolution and morphology). The results show
      that HAp particles with mesoporous structure could be produced. The size of HAp
      particles was approximately hundreds of nanometer. The pore width of HAp
      particles was in the range of 2.0-40 nm and the maximum centered around 4.5 nm.

PMID- 19771496
TI  - Characterization and genetic study of the ovine alphaS2-casein (CSN1S2) allele B.
AB  - An interesting and quite complex protein pattern has been described at ovine milk
      proteins but the genetic control of the variation observed was assessed only in
      few cases. The aim of this work was to characterize the ovine alpha ( s2 )-casein
      (CSN1S2) B variant, first observed in the Italian Gentile di Puglia, a fine
      wooled ovine breed, and to investigate its occurrence in two further breeds, the
      Sarda and Camosciata, which are the most widespread dairy breeds in Italy. The B
      variant differs from the most common form A with two amino acid exchanges:
      Asp(75) --> Tyr(75) and Ile(105) --> Val(105). The first substitution, resulting
      in a loss of a negative charge, is responsible for the higher isoelectric point
      of the B protein variant, which allows its detection by isoelectric focusing
      electrophoresis (IEF). The occurrence of CSN1S2*B in Sarda and Comisana was
      demonstrated. Since the Asp(75) --> Tyr(75) substitution modifies the protein
      electric charge, milk properties may result affected to some extent.

PMID- 19771495
TI  - Evaluation of drug-polymer miscibility in amorphous solid dispersion systems.
AB  - PURPOSE: To evaluate drug-polymer miscibility behavior in four different drug
      polymer amorphous solid dispersion systems, namely felodipine-poly(vinyl
      pyrrolidone) (PVP), nifedipine-PVP, ketoconazole-PVP, and felodipine-poly(acrylic
      acid) (PAA). MATERIALS AND METHODS: Amorphous solid dispersion samples were
      prepared at different drug-to-polymer ratios and analyzed using differential
      scanning calorimetry (DSC), mid-infrared (IR) spectroscopy, and powder X-ray
      diffractometry (PXRD). To help with interpretation of the IR spectra, principal
      components (PC) analysis was performed. Pair Distribution Functions (PDFs) of the
      components in the dispersion were determined from the PXRD data, and the pure
      curves of the components were also extracted from PXRD data using the Pure Curve
      Resolution Method (PCRM) and compared against experimentally obtained results.
      RESULTS: Molecular-level mixing over the complete range of concentration was
      verified for nifedipine-PVP and felodipine-PVP. For felodipine-PAA, drug-polymer
      immiscibility was verified for samples containing 30 to 70% polymer, while IR
      results suggest at least some level of mixing for samples containing 10 and 90%
      polymer. For ketoconazole-PVP system, partial miscibility is suspected, whereby
      the presence of one-phase amorphous solid dispersion system could only be
      unambiguously verified at higher concentrations of polymer. CONCLUSIONS: The
      three techniques mentioned complement each other in establishing drug-polymer
      miscibility in amorphous solid dispersion systems. In particular, IR spectroscopy
      and PXRD are sensitive to changes in local chemical environments and local
      structure, which makes them especially useful in elucidating the nature of
      miscibility in binary mixtures when DSC results are inconclusive or variable.

PMID- 19771497
TI  - George Tiller's legacy for genetic counseling.

PMID- 19771499
TI  - Quantifying the accuracy of forensic examiners in the absence of a "gold
      standard".
AB  - This study asked whether latent class modeling methods and multiple ratings of
      the same cases might permit quantification of the accuracy of forensic
      assessments. Five evaluators examined 156 redacted court reports concerning
      criminal defendants who had undergone hospitalization for evaluation or
      restoration of their adjudicative competence. Evaluators rated each defendant's
      Dusky-defined competence to stand trial on a five-point scale as well as each
      defendant's understanding of, appreciation of, and reasoning about criminal
      proceedings. Having multiple ratings per defendant made it possible to estimate
      accuracy parameters using maximum likelihood and Bayesian approaches, despite the
      absence of any "gold standard" for the defendants' true competence status.
      Evaluators appeared to be very accurate, though this finding should be viewed
      with caution.

PMID- 19771500
TI  - Parental autonomy-support, intrinsic life goals, and well-being among adolescents
      in China and North America.
AB  - Self-determination theory proposes that prioritizing intrinsic life goals, such
      as community involvement, is related to well-being, whereas focusing on extrinsic
      life goals, such as financial success, is associated with lower well-being and
      that parenting influences the type of life goals that youth adopt. In a sample of
      515 Chinese (56% female, mean age = 15.50) and 567 North American (52% male, mean
      age = 14.17) adolescents, a model of the relationships between parenting, life
      goals, and well-being was investigated and confirmed for intrinsic life goals.
      Across societies, autonomy-supportive parenting was associated with the
      endorsement of intrinsic life goals, which in turn was associated with well
      being. Intrinsic life goals partially mediated the relationship between parental
      autonomy-support and well-being. These findings suggest that, cross-culturally,
      prioritizing intrinsic life goals is related to increased well-being among
      adolescents and that parents could encourage intrinsic life goals by being
      supportive of their children's autonomy.

PMID- 19771501
TI  - Parental feeding practices and concerns related to child underweight, picky
      eating, and using food to calm differ according to ethnicity/race, acculturation,
      and income.
AB  - The purpose of this study was to examine differences in parental feeding
      practices according to ethnicity/race, household income, parent education level,
      acculturation (for Hispanic participants only), and participation in the Special
      Supplemental Nutrition Program for Women, Infants, and Children (WIC) program
      among parents living in a southern state in the United States. For this cross
      sectional study, parents of children ages 1-5 years living throughout Texas were
      recruited through random digit dialing with screening questions during Fall 2006.
      Eligible parents who agreed to participate completed the Preschooler Feeding
      Questionnaire (PFQ) and a demographic questionnaire over the phone in either
      English or Spanish. The PFQ included five subscales: child overeating concerns,
      child underweight concerns, difficulty with picky eating, using food to calm, and
      pushing child to eat. Demographic questions assessed ethnicity/race, household
      income, parent education level, acculturation, and WIC participation. Structural
      Equation Modeling (SEM), with the demographic variables as predictors, was used
      to predict the five PFQ subscales. Complete data were obtained from 721 parents,
      50% of whom were Hispanic. Significant differences for the PFQ subscales were
      noted for ethnicity/race, acculturation, and income level. Spanish-speaking
      Hispanic participants were significantly more worried about their child being
      underweight than English-speaking Hispanic participants. High-income non-WIC
      respondents were more likely to report that they have difficulty with picky
      eaters compared to WIC respondents. Spanish-speaking Hispanics and Black
      respondents were more likely than English-speaking Hispanics to use food to calm
      the child. Health practitioners need to be aware of differences in parental
      feeding practices and concerns among parents of diverse demographic backgrounds.
      Results from this study can be used to tailor health programs that promote
      healthy feeding practices among parents.

PMID- 19771503
TI  - Statewide systematic evaluation of sudden, unexpected infant death
      classification: results from a national pilot project.
AB  - The Centers for Disease Control and Prevention funded seven states, including
      Kentucky, to clarify statewide death certification practices in sudden,
      unexpected infant death and compare state performances with national
      expectations. Accurate assignment of the cause and manner of death in cases of
      sudden, unexpected infant death is critical for accurate vital statistics data to
      direct limited resources to appropriate targets, and to implement optimal and
      safe risk reduction strategies. The primary objectives are to (1) Compare SUID
      death certifications recommended by the KY medical examiners with the stated
      cause of death text field on the hard copy death electronic death certificates
      and (2) Compare KY and national SUID rates. Causes of death for SUID cases
      recommended by the medical examiners and those appearing on the hard copy and
      electronic death certificates in KY were collected retrospectively for 2004 and
      2005. Medical examiner recommendations were based upon a classification scheme
      devised by them in 2003. Coroners hard copy death certificates and the cause of
      death rates in KY were compared to those occurring nationally. Eleven percent of
      infants dying suddenly and unexpectedly did not undergo autopsy during the study
      interval. The KY 2003 classification scheme for SIDS is at variance with the
      NICHD and San Diego SIDS definitions. Significant differences in causes of death
      recommended by medical examiners and those appearing on the hard copy and
      electronic death certificates were identified. SIDS rates increased in KY in
      contrast to decreasing rates nationally. Nationwide adoption of a widely used
      SIDS definition, such as that proposed in San Diego in 2004 as well as
      legislation by states to ensure autopsy in all cases of sudden unexpected infant
      death are recommended. Medical examiners' recommendations for cause of death
      should appear on death certificates. Multidisciplinary pediatric death review
      teams prospectively evaluating cases before death certification is recommended.
      Research into other jurisdictions death certification process is encouraged.

PMID- 19771504
TI  - Using electronic drug monitor feedback to improve adherence to antiretroviral
      therapy among HIV-positive patients in China.
AB  - Effective antiretroviral therapy (ART) requires excellent adherence. Little is
      known about how to improve ART adherence in many HIV/AIDS-affected countries,
      including China. We therefore assessed an adherence intervention among HIV
      positive patients in southwestern China. Eighty subjects were enrolled and
      monitored for 6 months. Sixty-eight remaining subjects were randomized to
      intervention/control arms. In months 7-12, intervention subjects were counseled
      using EDM feedback; controls continued with standard of care. Among randomized
      subjects, mean adherence and CD4 count were 86.8 vs. 83.8% and 297 vs. 357
      cells/microl in intervention vs. control subjects, respectively. At month 12,
      among 64 subjects who completed the trial, mean adherence had risen significantly
      among intervention subjects to 96.5% but remained unchanged in controls. Mean CD4
      count rose by 90 cells/microl and declined by 9 cells/microl among intervention
      and control subjects, respectively. EDM feedback as a counseling tool appears
      promising for management of HIV and other chronic diseases.

PMID- 19771505
TI  - Coadministration of nanosystems of short silencing RNAs targeting oestrogen
      receptor alpha and anti-oestrogen synergistically induces tumour growth
      inhibition in human breast cancer xenografts.
AB  - The suppression of oestrogen receptor alpha (ERalpha) functions by silencing RNAs
      in association with or not with anti-oestrogens (AEs) both in vitro and in breast
      cancer cell xenografts was assessed. In vitro, a prolonged decrease in ERalpha
      protein expression and an enhanced AE-induced inhibition of ERalpha-mediated
      transcription, together with antiproliferative activity, were observed.
      Incorporation of ERalpha-siRNAs in pegylated nanocapsules (NC) was achieved; and
      their intravenous injections in MCF-7 xenografts, in contrast to scramble siRNA
      containing NCs, lead to decrease in ERalpha protein content and Ki67 labelling in
      tumour cells. The pure AE RU58668 (RU) both free and entrapped in stealth
      nanospheres (NS) at very low concentration (8 microg/kg/week) had no effect on
      tumour growth evolution. However, coinjection of the two nanocarriers potentiated
      the decrease in ERalpha protein, concomitantly with decreasing tumour vasculature
      and glucose transporter-1. These data support that the targeted delivery of
      ERalpha-siRNA in breast tumours potentiates the inhibition of E(2)-induced
      proliferative activity by encapsulated AE through enhanced anti-vascular
      activity. In the hormone-independent MDA-MB-231 xenograft model, RU-NS at 4
      mg/kg/week induce also a strong tumour vascular normalisation. Together, these
      findings suggest that the anti-oestrogen activity of RU as well as that of
      targeted ERalpha-siRNA leads to anti-angiogenic activity. Their delivery in
      stealth nanocarriers may constitute a new anti-cancer therapeutic strategy in
      solid tumours.

PMID- 19771506
TI  - Axillary nodal metastases from carcinoma of unknown primary  (CUPAx): a
      systematic review of published evidence.
AB  - Axillary lymph node metastases from adeno carcinoma or poorly differentiated
      carcinoma of unknown primary (CUPAx) represent a rare clinical entity without
      consensus on its biology, management and outcome. We systematically reviewed
      published CUPAx series and identified 24 retrospective studies enrolling 689
      patients from 1975 till 2006. CUPAx affected women at a mean age of 52 years, 66%
      of whom post-menopausal harbouring low-volume (N1, 48%) or high-volume (52%)
      nodal disease from ductal adenocarcinoma (83%). Among a total of 446 patients
      managed with mastectomy, a small breast primary was identified histologically in
      321 (72% of cases). Hormone receptor protein expression was observed in 40-50% of
      cases, while HER2 overexpression in 31%. CUPAx patients were managed with
      axillary lymph node dissection coupled to mastectomy (59%), primary breast
      irradiation (26%) or observation (15%). Observation was associated with high
      locoregional relapse rates (42%) and risk of metastatic spread. Mastectomy or
      radiotherapy provided locoregional disease control in 75-85% of cases, while
      adjuvant systemic therapy was associated with a nonsignificant trend for improved
      survival in few series. Five-year survival ranged from 59.4 to 88% at a median
      follow-up of 62 months (mean 5-year survival 72%), with axillary tumour burden
      being the pivotal prognostic factor. CUPAx is associated with similar
      presentation, biology and outcome to resected node-positive overt breast cancer
      and should be treated accordingly.

PMID- 19771507
TI  - Changes in the Body Image and Relationship Scale following a one-year strength
      training trial for breast cancer survivors with or at risk for lymphedema.
AB  - The aim of this study was to evaluate the impact of a twice-weekly strength
      training intervention on perceptions of body image in 234 breast cancer survivors
      (112 with lymphedema) who participated in the Physical Activity and Lymphedema
      (PAL) trial. The study population included two hundred and thirty-four women
      randomly assigned to twice-weekly strength training or control group that
      completed the 32-item Body Image and Relationships Scale (BIRS) at baseline and
      12 months. Percent change in baseline to 12-month BIRS total and subscale scores,
      upper and lower body strength, and general quality of life (QOL) were compared by
      intervention status. A series of multiple linear regression models including
      indicator variables for subgroups based on age, marital status, race, education,
      BMI, and strength change were used to examine differential intervention impact by
      subgroup. Strength and QOL variables were assessed as mediators of the
      intervention effect on BIRS. RESULTS: Baseline BIRS scores were similar across
      intervention and lymphedema status. Significantly greater improvement in BIRS
      total score was observed from baseline to 12 months in treatment vs. control
      participants (12.0 vs. 2.0%; P < 0.0001). A differential impact of the
      intervention on the Strength and Health subscale was observed for older women
      (>50 years old) in the treatment group (P = 0.03). Significantly greater
      improvement was observed in bench and leg press among treatment group when
      compared to control group participants, regardless of lymphedema. Observed
      intervention effects were independent of observed strength and QOL changes. Twice
      weekly strength training positively impacted self-perceptions of appearance,
      health, physical strength, sexuality, relationships, and social functioning.
      Evidence suggests the intervention was beneficial regardless of prior diagnosis
      of lymphedema. Strength and QOL improvements did not mediate the observed
      intervention effects.

PMID- 19771508
TI  - Association of low tumor RNA integrity with response to chemotherapy in breast
      cancer patients.
AB  - The CAN-NCIC-MA22 phase I/II clinical trial evaluated women with locally advanced
      or inflammatory breast cancer treated with epirubicin and docetaxel at 2 or 3
      weekly intervals in sequential cohorts. The relationship between various
      biomarkers and treatment response was assessed. Breast biopsy cores were obtained
      from 50 patients pre-, mid-, and post-treatment. Immunohistochemical staining was
      performed to determine baseline levels of estrogen receptor (ER), progesterone
      receptor (PR), Her2/Neu protein (HER2), and topoisomerase II (Topo 2),expressed
      as percent positive stain. Tumor RNA integrity(RIN) and tumor cellularity were
      measured pre-, mid- and post-treatment by capillary electrophoresis and light
      microscopy after hematoxylin/eosin staining, respectively.Associations between 1)
      maximum RIN and 2) tumor cellularity at the three time points with baseline
      levels of ER,PR, Her2, and topo II were assessed using Spearman and Pearson
      correlation coefficients. Associations between RIN and tumor cellularity with
      chemotherapy dose level orpathologic response were assessed using one-way
      ANOVA.In this study, we observed that low mid-treatment maximum RIN (but not
      tumor cellularity) was associated with high chemotherapy drug dose level (P =
      0.05) and eventual pathologic complete response (pCR) (P = 0.01).
      Posttreatment,low maximum RIN was found to be associated with low tumor
      cellularity (P = 0.004), and low tumor cellularity with pCR (P = 0.01). Post
      treatment tumor cellularity was lowest in patients with tumors having high
      baseline PR levels (P = 0.05). The association of midtreatment RIN with drug dose
      level and with pCR suggests that tumor RIN may represent an important new
      biomarker for measuring response to chemotherapy in breast cancer patients.

PMID- 19771509
TI  - Increased cytotoxic and genotoxic tolerance of Eisenia fetida (Oligochaeta) to
      cadmium after long-term exposure.
AB  - Since life-cycle studies showed that the earthworm species Eisenia fetida can
      develop increased tolerance after long-term exposure to a sub-lethal
      concentration of Cd in the laboratory, we assessed both the cytotoxicity and
      genotoxicity of Cd in a long-term Cd-exposed population. We exposed E. fetida
      specimens from this population, from a laboratory control population and from a
      field population to various concentrations of CdSO(4) in artificial soil water.
      Toxic effects were measured using the MTT test and the comet assay. The group
      that had been exposed to Cd for more than a decade was found to be more tolerant
      to the deleterious effects of Cd at both cellular and molecular levels than the
      laboratory control population. The field population, which came from a severely
      metal polluted environment, displayed high tolerance at molecular level as well.
      The results provide novel biomarker evidence of increased Cd tolerance in E.
      fetida, but the mechanisms supporting the apparent tolerance, still need to be
      clarified.

PMID- 19771510
TI  - A biology-based approach for mixture toxicity of multiple endpoints over the life
      cycle.
AB  - Typical approaches for analyzing mixture ecotoxicity data only provide a
      description of the data; they cannot explain observed interactions, nor explain
      why mixture effects can change in time and differ between endpoints. To improve
      our understanding of mixture toxicity we need to explore biology-based models. In
      this paper, we present an integrated approach to deal with the toxic effects of
      mixtures on growth, reproduction and survival, over the life cycle.
      Toxicokinetics is addressed with a one-compartment model, accounting for effects
      of growth. Each component of the mixture has its own toxicokinetics model, but
      all compounds share the effect of body size on uptake kinetics. The toxicodynamic
      component of the method is formed by an implementation of dynamic energy budget
      theory; a set of simple rules for metabolic organization that ensures
      conservation of mass and energy. Toxicant effects are treated as a disruption of
      regular metabolic processes such as an increase in maintenance costs. The various
      metabolic processes interact, which means that mixtures of compounds with certain
      mechanisms of action have to produce a response surface that deviates from
      standard models (such as 'concentration addition'). Only by separating these
      physiological interactions from the chemical interactions between mixture
      components can we hope to achieve generality and a better understanding of
      mixture effects. For example, a biology-based approach allows for educated
      extrapolations to other mixtures, other species, and other exposure situations.
      We illustrate our method with the interpretation of partial life-cycle data for
      two polycyclic aromatic hydrocarbons in Daphnia magna.

PMID- 19771511
TI  - Temporal bacterial diversity associated with metal-contaminated river sediments.
AB  - The temporal activity, abundance and diversity of microbial communities were
      evaluated across a metal-contamination gradient around a Superfund site in
      Montana. In order to analyze short-term variability, samples were collected from
      six sites on four occasions over 12 months. Measurements of community activity,
      diversity and richness, quantified by dehydrogenase activity and through
      denaturant gradient gel electrophoresis (DGGE), respectively, were higher at
      contaminated sites adjacent to the smelter, relative to reference sites. 16S rRNA
      gene copy numbers, measured by quantitative PCR, showed seasonal variability, yet
      were generally higher within polluted sediments. Jaccard similarity coefficients
      of DGGE profiles, found sites to cluster based primarily on geographical
      proximity rather than geochemical similarities. Intra-site clustering of the most
      polluted sites also suggests a stable metal-tolerant community. Sequences from
      DGGE-extracted bands were predominantly Beta and Gammaproteobacteria, although
      the communities at all sites generally maintained a diverse phylogeny changing in
      composition throughout the sampling period. Spearman's rank correlations analysis
      found statistically significant relationships between community composition and
      organic carbon (r-value = 0.786) and metals (r-values As = 0.65; Cu = 0.63; Zn =
      0.62). A diverse and abundant community at the most polluted site indicates that
      historical contamination selects for a metal-resistant microbial community, a
      finding that must be accounted for when using the microbial community within
      ecosystem monitoring studies. This study highlights the importance of using
      multiple time-points to draw conclusions on the affect of metal contamination.

PMID- 19771512
TI  - Mercury concentrations in wetlands associated with coal-fired power plants.
AB  - There have been contradictory reports of the relative proportion of mercury from
      coal-fired power plants that deposits locally. Our objective was to determine any
      local effect of coal-fired power plants on total mercury concentrations in
      wetland sediment and tadpole samples. Four power plants and 45 wetlands were
      selected for study. Total mercury concentrations were determined in 75 sediment
      samples (range: 8-82 ng/g dry weight) and 100 bullfrog (Lithobates catesbeiana)
      and green frog (Lithobates clamitans) tadpoles (range: 5-318 ng/g wet weight).
      Tadpole and sediment total mercury did not significantly vary by power plant or
      distance from the plant. Only one power plant had a significantly greater
      concentration of total mercury in sediment downwind compared to upwind wetlands.
      A similar (but non-significant) trend was found for tadpole total mercury
      surrounding the same plant. Tadpole total mercury was negatively correlated with
      both tadpole weight and total length. Tadpole and sediment total mercury
      concentrations were not significantly correlated with one another. The results of
      the current study suggest that coal-fired power plants are not significantly
      affecting mercury concentrations in surrounding wetlands.

PMID- 19771513
TI  - Preliminary evaluation on the use of homing pigeons as a biomonitor in urban
      areas.
AB  - This study evaluates the usefulness of homing pigeons as a biomonitor of
      polycyclic aromatic hydrocarbons (PAHs) in urban environments. The mean
      concentrations of total PAHs in liver and lung tissues were greater in pigeons
      from Beijing compared to pigeons from Chengdu, however, this difference was only
      statistically significant for PAH concentrations in liver tissue (P < 0.05).
      Similarly, the severity of anthracosis or pneumoconiosis in lung tissue and
      hepatitis in liver tissue was greater in pigeons from Beijing compared to pigeons
      from Chengdu. Low molecular weight PAHs dominated the contribution of individual
      PAHs in both tissues. Significant differences (P < 0.05) were observed for most
      low and moderate molecular weights PAHs in liver and for some low and high
      molecular weights PAHs in lung between the two cites. The profile patterns of
      individual PAHs were similar between lung tissue of pigeons and between local
      ambient airs in summer for both cities, whereas the profile patterns between
      liver tissue and pigeon food were less similar. These data suggest that homing
      pigeons may be of value as a biomonitor of environmental pollution in urban
      areas.

PMID- 19771514
TI  - Effect of purple sweet potato anthocyanins on beta-amyloid-mediated PC-12 cells
      death by inhibition of oxidative stress.
AB  - Amyloid-beta peptide (Abeta) is known to induce the redox imbalance,
      mitochondrial dysfunction and caspase activation, resulting in neuronal cell
      death. Treatment with antioxidants provided a new therapeutic strategy for
      Alzheimer's disease (AD) patients. Here we investigate the effects of purple
      sweet potato anthocyanins (PSPA), the known strong free radical scavengers, on
      Abeta toxicity in PC12 cells. The results showed that pretreatment of PC12 cells
      with PSPA reduced Abeta-induced toxicity, intracellular reactive oxygen species
      (ROS) generation and lipid peroxidation dose-dependently. In parallel, cell
      apoptosis triggered by Abeta characterized with the DNA fragmentation and caspase
      3 activity were also inhibited by PSPA. The concentration of intracellular Ca(2+)
      and membrane potential loss associated with cell apoptosis were attenuated by
      PSPA. These results suggested that PSPA could protect the PC-12 cell from Abeta
      induced injury through the inhibition of oxidative damage, intracellular calcium
      influx, mitochondria dysfunction and ultimately inhibition of cell apoptosis. The
      present study indicates that PSPA may be a promising approach for the treatment
      of AD and other oxidative-stress-related neurodegenerative diseases.

PMID- 19771516
TI  - Reduced somatostatin in hypothalamus of young male mouse increases local but not
      circulatory GH.
AB  - The release of growth hormone (GH) from the pituitary gland is primarily
      inhibited by somatostatin (SRIF) from the hypothalamus via interactions with five
      types of SRIF receptors (SSTRs). However, the inhibition mechanism of SRIF on GH
      has not been fully examined. In this study, we repressed the hypothalamic SRIF in
      young male mice by stereotaxic injection of the lentiviral-shRNA against SRIF to
      investigate the role of hypothalamic SRIF on hormone secretion in the GH/IGF-1
      axis. We found that the reduction of SRIF in hypothalamus was associated with an
      increase in the protein, but not the mRNA level, of the GH in the pituitary where
      SSTR 2 and SSTR 5 act importantly. Interestingly, the level of blood circulatory
      SRIF, GH, IGF-1 and the body weight were not significantly influenced by the
      downregulation of hypothalamic SRIF. Our findings provide insights into the
      mechanisms underlying the inhibition of SRIF on GH secretion.

PMID- 19771515
TI  - Neuroprotective effect of KB-R7943 against glutamate excitotoxicity is related to
      mild mitochondrial depolarization.
AB  - KB-R7943, an inhibitor of a reversed Na(+)/Ca(2+) exchanger, exhibits
      neuroprotection against glutamate excitotoxicity. Taking into consideration that
      prolonged exposure of neurons to glutamate induces delayed calcium deregulation
      (DCD) and irreversible decrease of mitochondrial membrane potential
      (Deltapsi(mit)), we examined the effect of KB-R7943 on glutamate and kainate
      induced [Ca(2+)](i) and on Deltapsi(mit) changes in rat cultured cerebellar
      granule neurons. 15 micromol/l KB-R7943 significantly delayed the onset of DCD in
      response to kainate but not in response to glutamate. In spite of [Ca(2+)](i)
      overload, KB-R7943 considerably improved the [Ca(2+)](i) recovery and restoration
      of Deltapsi(mit) after glutamate and kainate washout and increased cell viability
      after glutamate exposure. In resting neurons, KB-R7943 induced a statistically
      significant decrease in Deltapsi(mit). KB-R7943 also depolarized isolated brain
      mitochondria and slightly inhibited mitochondrial Ca(2+) uptake. These findings
      suggest that mild mitochondrial depolarization and diminution of Ca(2+)
      accumulation in the organelles might contribute to neuroprotective effect of KB
      R7943.

PMID- 19771517
TI  - Religion and spirituality: how clinicians in quebec and geneva cope with the
      issue when faced with patients suffering from chronic psychosis.
AB  - Spirituality and religion have been found to be important in the lives of many
      people suffering from severe mental disorders, but it has been claimed that
      clinicians "neglect" their patients' religious issues. In Geneva, Switzerland and
      Trois-Rivieres, Quebec, 221 outpatients and their 57 clinicians were selected for
      an assessment of religion and spirituality. A majority of the patients reported
      that religion was an important aspect of their lives. Many clinicians were
      unaware of their patients' religious involvement, even if they reported feeling
      comfortable with the issue. Both areas displayed strikingly similar results,
      which supports their generalization.

PMID- 19771518
TI  - Fidelity and outcomes in six integrated dual disorders treatment programs.
AB  - Fidelity scores and outcomes were measured in six outpatient programs in
      California which implemented Integrated Dual Disorders Treatment (IDDT). Outcomes
      were measured for 1 year in four sites and 2 years in two sites; fidelity was
      assessed at 6 month intervals. Three of the six sites achieved high fidelity (at
      least a 4 on a 5 point fidelity scale) and three moderate fidelity (at least a
      3). Retention in treatment, mental health functioning, stage of substance abuse
      treatment, abstinence, and psychiatric hospitalization were measured. Outcomes
      for individual programs were generally positive but not consistent within
      programs or across programs. Using pooled data in a longitudinal regression model
      with random effects at person level and adjustment of standard errors for
      clustering by site, change over time was not statistically significant for the
      primary outcomes. Fidelity scores had limited association with positive outcomes.

PMID- 19771519
TI  - Differential modulation of mitochondrial OXPHOS system during HIV-1 induced T
      cell apoptosis: up regulation of Complex-IV subunit COX-II and its possible
      implications.
AB  - Human Immunodeficiency Virus-1 (HIV-1) infection leads to CD4+ T cell depletion
      primarily by apoptosis employing both intrinsic and extrinsic pathways. Although
      extensive literature exists about the role of mitochondrial proteins in HIV
      induced T cell apoptosis, there is little understanding about the role of
      different components of mitochondrial oxidative phosphorylation (OXPHOS) system
      in apoptosis. The OXPHOS system comprises of five enzyme complexes (Complex I,
      II, III, IV, V), subunits of which have been implicated in various functions in
      addition to their primary role in energy generating process. Here using
      differential gene expression analysis, we report that Cytochrome Oxidase-II (COX
      II), a subunit of Complex-IV is induced in HIV infected apoptotic T-cells. We
      also observe a temporal up regulation of this subunit across different T-cell
      lines and in human PBMCs. Further analysis indicates increase in expression of
      majority of Complex-IV subunits with concomitant increase in Complex-IV activity
      in HIV infected T cells. Silencing of COX-II expression leads to reduced
      apoptosis in infected T-cells, indicating its importance in apoptosis.
      Furthermore, our results also show that the activities of enzyme complexes I, II
      and III are decreased while those of Complex IV and V are increased at the time
      of acute infection and apoptosis. This differential regulation in activities of
      OXPHOS system complexes indicate a complex modulation of host cell energy
      generating system during HIV infection that ultimately leads to T cell apoptosis.

PMID- 19771520
TI  - Endoplasmic reticulum stress mediates gamma-tocotrienol-induced apoptosis in
      mammary tumor cells.
AB  - gamma-Tocotrienol, a member of the vitamin E family of compounds, induces
      apoptosis in a variety of cancer cell types. However, previous studies have
      clearly demonstrated that gamma-tocotrienol-induced apoptosis in neoplastic mouse
      +SA mammary epithelial cells is not mediated through mitochondrial stress or
      death receptor apoptotic signaling. Therefore, studies were conducted to
      determine the role of endoplasmic reticulum (ER) stress in mediating gamma
      tocotrienol-induced apoptosis in +SA mammary tumor cells. Treatment with 15-40
      microM gamma-tocotrienol induced +SA cell death in a dose-responsive manner, and
      these effects were associated with a corresponding increase in poly (ADP-ribose)
      polymerase (PARP)-cleavage and activation of protein kinase-like endoplasmic
      reticulum kinase/eukaryotic translational initiation factor/activating
      transcription factor 4 (PERK/eIF2alpha/ATF-4) pathway, a marker of ER stress
      response. These treatments also caused a large increase in C/EBP homologous
      protein (CHOP) levels, a key component of ER stress mediated apoptosis that
      increases expression of tribbles 3 (TRB3). Knockdown of CHOP by specific siRNAs
      attenuated gamma-tocotrienol-induced PARP-cleavage, CHOP and TRB3 expression.
      gamma-Tocotrienol treatment also reduced full-length caspase-12 levels, an
      indication of caspase-12 cleavage and activation. Intracellular levels of 3
      hydroxy-3-methylglutaryl-coenzyme A (HMGCoA) reductase, an ER-transmembrane
      enzyme catalyzing the synthesis of mevalonate, decreased following gamma
      tocotrienol treatment, but combined treatment with mevalonate did not reverse
      gamma-tocotrienol-induced apoptosis, suggesting that a decrease in HMGCoA
      reductase activity is not required for gamma-tocotrienol induced apoptosis. These
      results demonstrate that ER stress apoptotic signaling is associated with gamma
      tocotrienol-induced apoptosis in +SA mammary tumor cells.

PMID- 19771521
TI  - Multiple alphaII-spectrin breakdown products distinguish calpain and caspase
      dominated necrotic and apoptotic cell death pathways.
AB  - Apoptosis and oncotic necrosis in neuronal and glial cells have been documented
      in many neurological diseases. Distinguishing between these two major types of
      cell death in different neurological diseases is needed in order to better reveal
      the injury mechanisms so as to open up opportunities for therapy development.
      Accumulating evidence suggests apoptosis and oncosis epitomize the extreme ends
      of a broad spectrum of morphological and biochemical events. Biochemical markers
      that can distinguish between the calpain and caspase dominated types of cell
      death would help in this process. In this study, three chemical agents,
      maitotoxin (MTX), staurosporine (STS) and thylenediaminetetraacetic acid (EDTA),
      were used to induce different types of cell death in PC12 neuronal-like cells.
      MTX-induced necrosis, as determined by the increased levels of calpain-specific
      cleaved fragments of spectrin by antibodies specific to the calpain-cleaved 150
      kDa alphaII-spectrin breakdown product (SBDP150) and 145 kDa alphaII-spectrin
      breakdown product (SBDP145). In this paradigm, there were no detectable SBDP150i
      and SBDP120 fragments as determined by antibodies specific to the caspase-cleaved
      specific fragments similar to those seen in the EDTA-mediated apoptotic PC-12
      cells. In contrast to the calpain specific MTX necrosis treatment and the caspase
      EDTA apoptotic treatment is the STS treatment which induced both proteases as
      shown by the increase in all the SBDP fragments. Furthermore, compared to
      SBDP150, SBDP145 appears to be a more specific and sensitive biomarker for
      calpain activation. Taken together, our results suggested calpains and caspases
      which dominate the two major types of cell death could be independently
      discriminated by specifically examining the multiple alphaII-spectrin cleavage
      breakdown products.

PMID- 19771522
TI  - Health promotion or disease prevention: a real difference for public health
      practice?
AB  - It appears that there are two distinct practices within public health, namely
      health promotion and disease prevention, leading to different goals. But does the
      distinction hold? Can we promote health without preventing disease, and vice
      versa? The aim of the paper is to answer these questions. First, the central
      concepts are defined and the logical relations between them are spelt out. A
      preliminary conclusion is that there is a logical difference between health and
      disease, which makes health promotion and disease prevention two distinct
      endeavours. However, since disease is defined in relation to health, as those
      kinds of internal processes and states that typically lead to ill health, the
      difference is smaller than it might appear. Second, in order to answer the
      practical question whether it is possible to promote health without preventing
      disease, and vice versa, several kinds of public health interventions are
      discussed. The conclusion is that while health promotion and disease prevention
      can be distinguished conceptually, they can hardly be distinguished in practice.
      Most general measures do both at the same time.

PMID- 19771523
TI  - Cushing disease as possible cause of persistent growth failure despite growth
      hormone therapy in a small for gestational age male.
AB  - Growth hormone (GH) therapy in children with small for gestational age (SGA) has
      been shown to be of significant therapeutic benefit. We report the case of an 11
      year-old Caucasian male who developed early adrenarche, hypertension and insulin
      resistance on GH therapy for SGA and profound short stature (ht -5 SD). This
      patient demonstrated a poor response to GH therapy and developed physical and
      biochemical findings of insulin resistance responsive to metformin therapy. He
      remained hypertensive, however, and continued to have elevated serum
      dehydroepiandrosterone sulfate levels. Urinary free cortisol excretion was
      subsequently found to be elevated. The diagnosis of Cushing's disease was
      confirmed with inferior petrosal sinus sampling and pituitary MRI. The patient
      underwent partial adenohypophysectomy with resulting normalization of plasma
      cortisol levels and associated symptoms. Our patient's diagnosis of Cushing's
      disease was complicated by his past history of poor growth since birth and
      history of SGA. The signs of Cushing's disease did not overtly appear until GH
      therapy was initiated to help treat severe short stature. It is possible that the
      metabolic effects of GH therapy unmasked the presence of underlying Cushing's
      disease.

PMID- 19771525
TI  - MicroRNA-17-3p is a prostate tumor suppressor in vitro and in vivo, and is
      decreased in high grade prostate tumors analyzed by laser capture
      microdissection.
AB  - MicroRNAs (miRs) are a novel class of RNAs with important roles in regulating
      gene expression. To identify miRs controlling prostate tumor progression, we
      utilized unique human prostate sublines derived from the parental P69 cell line,
      which differ in their tumorigenic properties in vivo. Grown embedded in laminin
      rich extracellular matrix (lrECM) gels these genetically-related sublines
      displayed drastically different morphologies correlating with their behaviour in
      vivo. The non-tumorigenic P69 subline grew as multicellular acini with a defined
      lumen and basal/polar expression of relevant marker proteins. M12, a highly
      tumorigenic, metastatic derivative, grew as a disorganized mass of cells with no
      polarization, whereas the F6 subline, a weakly tumorigenic, non-metastatic M12
      variant, reverted to acini formation akin to the P69 cell line. These sublines
      also differed in expression of vimentin, which was high in M12, but low in F6 and
      P69 sublines. Analysis of vimentin's conserved 3'-UTR suggested several miRs that
      could regulate vimentin expression. The lack of miR-17-3p expression correlated
      with an increase in vimentin synthesis and tumorigenicity. Stable expression of
      miR-17-3p in the M12 subline reduced vimentin levels 85% and reverted growth to
      organized, polarized acini in lrECM gels. In vitro motility and invasion assays
      suggested a decrease in tumorigenic behaviour, confirmed by reduced tumor growth
      in male athymic, nude mice dependent on miR-17-3p expression. Analysis of LCM
      purified clinical human prostatectomy specimens confirmed that miR-17-3p levels
      were reduced in tumor cells. These results suggest that miR-17-3p functions as a
      tumor suppressor, representing a novel target to block prostate tumor
      progression.

PMID- 19771524
TI  - Bladder cancer.
AB  - Bladder cancer is a complex disease of older patients with coexisting medical
      problems requiring multimodal therapy. For patients with localized bladder
      cancer, standard management for superficial disease includes transurethral
      resection with or without intravesical therapy, while muscle-invasive cancer is
      managed with neoadjuvant cisplatin- based chemotherapy followed by radical
      cystectomy. Comorbid conditions prevent many older patients from receiving
      cisplatin-based chemotherapy and/or undergoing surgery. Tri-modality bladder
      preservation approaches including a complete transurethral resection of the
      bladder tumor (TURBT) followed by combined chemotherapy and radiation have
      generally included only those patients who are candidates for a salvage
      cystectomy. Future research must specifically focus on older adults with bladder
      cancer including non-cisplatin-based neoadjuvant regimens; bladder preservation
      strategies using alternative non-cisplatin chemotherapy in noncystectomy
      candidates; clinical trials evaluating novel targeted agents in older adults; and
      geriatric assessment tools to assist in decision making.

PMID- 19771526
TI  - Cloning, purification and bioactivity assay of human CD28 single-chain antibody
      in Escherichia coli.
AB  - Engineered single chain antibodies have become a powerful source of immunotherapy
      against a wide range of diseases. Here, we present the generation of human CD28
      single-chain antibody gene (CD28-ScFv), which contained variable fragments of
      heavy chain and light chain (VH and VL) of the anti-CD28 antibody, and a linking
      peptide (Gly4Ser)3 inserted in the middle of VH and VL. The fused gene CD28-ScFv
      was successfully expressed in BL21 (DE3) cells and confirmed by western blotting
      assay. The molecular weight of CD28-ScFv was 43 kDa and the major fraction was
      expressed as an insoluble body. By dissolving the insoluble bodies, renaturing in
      vitro and purifying with a Ni-NTA affinity column, highly purified expression
      products of CD28-ScFv were obtained. This product could recognize and bind to
      CD28+ positive T cells. The proliferation capacity of peripheral blood T cells
      was increased by purified CD28-ScFv. In this study, we improved orthodox
      renaturing techniques by combining the dilution renaturation with phase gradient
      dialysis. With this new method, highly purified CD28-ScFv products were developed
      and biological activity of the products was similar to that of the mouse
      monoclonal anti-human CD28 antibody.

PMID- 19771527
TI  - Characterization of a pollen-preferential gene OSIAGP from rice (Oryza sativa L.
      subspecies indica) coding for an arabinogalactan protein homologue, and analysis
      of its promoter activity during pollen development and pollen tube growth.
AB  - During differential screening of inflorescence-specific cDNA libraries from Oryza
      sativa indica, an arabinogalactan protein (OSIAGP) cDNA (586 bp) expressing
      preferentially in the inflorescence has been isolated. It encodes an
      arabinogalactan protein of 59 amino acids (6.4 kDa) with a transmembrane domain
      and a secretory domain at the N terminus. The protein shows homology with AGP23
      from Arabidopsis, and its homologue in japonica rice is located on chromosome 6.
      OSIAGP transcripts also accumulate in shoots and roots of rice seedling grown in
      the dark, but light represses expression of the gene. Analysis of a genomic clone
      of OSIAGP revealed that its promoter contains several pollen-specificity and
      light-regulatory elements. The promoter confers pollen-preferential activity on
      gus, starting from the release of microspores to anther dehiscence in transgenic
      tobacco, and is also active during pollen tube growth. Analysis of pollen
      preferential activity of the promoter in the transgenic rice system revealed that
      even the approximately 300 bp fragment has activity in pollen and the anther wall
      and further deletion down to approximately 100 bp completely abolishes this
      activity, which is consistent with in-silico analysis of the promoter.
      Arabinogalactan proteins have been shown to be involved in the cell elongation
      process. The homology of OSIAGP with AGP23 and the fact that seedling growth in
      the dark and pollen tube growth are events based on cell elongation strengthen
      the possibility of OSIAGP performing a similar function.

PMID- 19771528
TI  - Pharmacy students' attitudes toward pharmaceutical care in Riyadh region Saudi
      Arabia.
AB  - AIM OF THE STUDY: The objectives of the study were to investigate and describe
      the attitude of Saudi pharmacy students toward pharmaceutical care. METHOD: A
      survey of pharmacy students (8th-10th educational levels) was conducted from
      September to December 2006, in college of pharmacy King Saud University, Riyadh.
      The students completed a self-administered questionnaire designed to test the
      study objectives. The instrument (Standard Pharmaceutical Care Attitudes Survey,
      PCAS) used in the questionnaire was developed and revalidated in USA. Descriptive
      statistics on the sample characteristics and questionnaire items include means,
      standard deviation and frequency distribution. Student's t test and one-way ANOVA
      were used for inferential statistics. RESULTS: A total of 214 students (85.6%
      response rate) completed the questionnaire. The Cronbach alpha was found to be
      0.792. Of the respondents, 95.2% felt that pharmaceutical care movement will
      improve patient health, 94.9% thought that the practice of pharmaceutical care is
      valuable, 85% "strongly agree" or "agree" that all pharmacists should perform
      pharmaceutical care, whereas, about two third (64.5%) "strongly agree" or "agree"
      that students should perform pharmaceutical care during their clerkships. The
      rated scores and factor loading, which are used to determine items that belong to
      the group responses, were reported. Determination of communalities revealed no
      item had loading factor of <0.4 and therefore, the mean total score was computed
      to be 56.17 +/- 0.29019. Females had significantly higher positive attitudes than
      their male counterparts, and this were also associated with age and marital
      status. CONCLUSION: Saudi pharmacy students in the study indicated favorable
      positive attitudes toward pharmaceutical care, and the attitude ratings were
      associated with age, sex and marital status. A nationwide survey including all
      pharmacy faculties would provide further evidence. The validity of PCAS needs
      cross validation in Saudi Arabia.

PMID- 19771529
TI  - Molecular cloning and sexually dimorphic expression of DMRT4 gene in Oreochromis
      aureus.
AB  - The DM-domain gene family has at least eight members with conserved DNA-binding
      DM-domain, which encodes putative transcription factors related to the sexual
      regulator Dsx of Drosophila and Mab-3 of C. elegans. Although some of the DM
      genes are involved in sexual development, the function of most of these genes
      remains unclear. In this study, rapid amplification cDNA ends (RACE) was used for
      the isolation of DMRT4 full-length cDNA from the ovary of the blue tilapia
      Oreochromis aureus. The full-length of DMRT4 cDNA was 1,571 bp, containing the
      148 bp 5'-untranslated region, 193 bp 3'-untranslated region and 1,230 bp open
      reading frame. The deduced amino acid sequence of the open reading frame (ORF)
      encoded a protein of 409 amino acids with a theoretical pI of 8.492 and a
      calculated molecular weight of 44.12 kDa. One conserved functional domain, DM
      domain was identified in blue tilapia DMRT4. The DMRT4 full-length gene obtained
      from the blood was 1,741 bp, containing a 156 bp intron. Phylogenetic analysis
      indicated that the amino acid sequences encoded by DMRT4 genes from different
      species had a high degree of sequence identity as revealed in phylogenetic tree
      constructed. Real-time quantitative Reverse-Transcription Polymerase Chain
      Reaction (RT-PCR) was used to analyze the expression patterns of DMRT4 in
      different developmental stages and different tissues in Oreochromis aureus. DMRT4
      mRNA was detected from early gastrulae stage during embryonic development, and
      maintained a considerable high level until 1 day post hatching. With the increase
      of age, enhanced DMRT4 mRNA was observed in ovary and brain. After 15 and 30
      days, fries treated with 17beta-estradiol had a significant increase in DMRT4
      mRNA levels compared with the control fries (P < 0.05). DMRT4 was found to be
      expressed in the ovary and endbrain, thalamencephalon, pituitary, not detected in
      the liver, kidney, spleen, heart and muscle of adult fish. These results showed
      that the DMRT4 gene have potentially important roles in gonadal development and
      may have contributed to the functional endocrine axis. Our study provides
      fundamental understanding to the structure and functions of DMRT4 protein and the
      mechanisms of sex control in Oreochromis aureus.

PMID- 19771531
TI  - Effects of Lewis Y antigen on the gene expression of multiple drug resistance
      associated proteins in human ovarian cancer RMG-I-H cells.
AB  - The effects of Lewis Y antigen on the gene expression of multiple drug resistance
      associated proteins in human ovarian cancer RMG-I-H cells were unclear by now. In
      this study, we detected the gene expression of multiple drug resistance
      associated proteins (MRP) in RMG-I-H cells and RMG-I-H cells treated with anti
      Lewis Y monoclonal antibody to investigate the association between Lewis Y
      antigen and the gene expression of drug resistance-associated proteins. Compared
      with RMG-I cells, the expression of MRP1, MRP2, protein kinase C-alpha (PKC
      alpha), and topoisomerase I (Topo I) mRNAs in RMG-I-H cells were significantly
      upregulated, while the MDR-1 mRNA was downregulated. Immunochemistry analyses
      indicated that the in vitro and in vivo expression levels of MDR-1 protein (P-gp)
      in RMG-I-H cells were significantly higher than those in RMG-I cells. After RMG-I
      H cells were treated with anti-Lewis Y monoclonal antibody, the expression levels
      of MDR-1, MRP1, MRP2, PKC-alpha, and Topo I mRNAs gradually decreased with the
      prolongation of treatment duration. In contrast, no obvious changes were noted in
      the expression levels of these mRNAs in the non-treatment group. At 6 h after
      treatment, the relative levels of MDR-1, MRP1, MRP2, PKC-alpha, and Topo I mRNAs
      in the antibody treatment group were significantly lower than those in the non
      treatment group. In conclusion, Lewis Y antigen is closely associated with
      regulating the gene expression of multiple drug resistance-associated proteins.

PMID- 19771532
TI  - Quality of life and depression among metastatic breast cancer patients.
AB  - Depression is seen in many cancer patients. It is common in the general
      population and in adults and children with cancer and frequently coexists with
      anxiety and pain. The pilot study evaluated the level of the global quality of
      life (QoL) and the incidence and the relevance of the depression among metastatic
      breast cancer patients in a programme of palliative cancer care. The study is
      prospective and cross-sectional. Dates were obtained during year 2008 among 41
      patients. The mean age of all 41 subjects was 58 years old (aged 41-80 years
      old). The Czech version of Zung self-rating depression scale was performed for
      the evaluation of the depression. The Czech version of generic European Quality
      of Life Questionnaire EQ-5D was performed for the evaluation of the level of
      global QoL. The statistical evaluation presents that mean ZSDS (Zung self-rating
      depression score) certifies the presence of the signs of the moderate depression
      among metastatic breast cancer patients (ZSDS range was 60-69). The incidence of
      the depression was 61% (25 of all 41 subjects). The relevance of the depression
      is characterized: the severe depression was proved in five of all 25 subjects,
      the moderate depression in 10 of all 25 subjects, and the mild depression in 10
      of all 25 subjects. The global QoL among metastatic breast cancer patients is on
      very low level. The mean EQ-5D score (dimension of QoL) was 55%. The mean EQ-5D
      VAS (subjective health status) was 59.2%. The results showed that subsist
      association between metastatic breast cancer, depression, and the low level of
      the global QoL.

PMID- 19771533
TI  - Myoepithelial carcinoma of the retromolar area in a young female. A rare case
      report.
AB  - We present a case of a 34-year-old woman with myoepithelial carcinoma of the
      retromolar area. Myoepithilial carcinoma is a rare tumor of small salivary glands
      most usually located in the parotid gland. The major differential diagnosis of
      myoepithelioma is from pleomorphic adenoma. Little is known about the clinical
      and biological behavior and the prognosis of myoepithelial carcinoma and there is
      no consensus for its treatment. It is considered a low-grade malignancy; it
      sometimes shows aggressive behavior and may locally recur. Our patient was
      treated successfully with wide-local resection and remained free of disease for 6
      months.

PMID- 19771534
TI  - A case-control study of reproductive factors associated with subtypes of breast
      cancer in Northeast China.
AB  - Based on the expression of estrogen receptor (ER), progesterone receptor (PR) and
      HER2/neu (HER2), breast cancer is classified into several subtypes: luminal A
      (ER+ and/or PR+, HER2-), luminal B (ER+ and/or PR+, HER2+), HER2-overexpressing
      (ER-, PR-, and HER2+) and triple-negative (ER-, PR-, and HER2-). The aim of this
      case-control study is to determine reproductive factors associated with breast
      cancer subtypes in Chinese women. A total of 1,417 patients diagnosed with breast
      cancer in the First Affiliated Hospital, China Medical University, Shenyang,
      China between 2001 and 2009 and 1,587 matched controls without a prior breast
      cancer were enrolled. Personal interviews were conducted to obtain information on
      reproductive characteristics and clinical history. Relationships between the
      factors and the subtypes of breast cancer were examined using logistic regression
      to compute odds ratios (OR) and 95% confidence intervals (CI). Notably, luminal A
      (50.0%) was the most prevalent subtype relative to luminal B (15.10%), HER2
      overexpressing (10.87%) and triple-negative (23.08%). Menarche at an early age
      was associated with a reduced risk of luminal A (OR, 2.35; 95% CI, 1.45-3.81).
      Breastfeeding protected parous women from any subtype of breast cancer.
      Postmenopause and spontaneous abortion were inversely associated with the risk of
      luminal tumors. By contrast, multiparity, family history of breast cancer and
      induced abortion increased the risk of breast cancer. Collectively, our findings
      suggest that reproductive factors such as age at menarche, parity, breastfeeding,
      menopausal status and abortion history have different effects on the subtypes of
      breast cancer in Chinese women.

PMID- 19771535
TI  - Exacerbation of chronic idiopathic thrombocytopenic purpura following
      reactivation of an occult hepatitis B.
AB  - Immune thrombocytopenia is a disease mediated by platelet autoantibodies that
      accelerate platelet destruction and inhibit their production. Most cases are
      considered idiopathic, whereas others are secondary to coexisting conditions such
      as infectious diseases. All hepatotropic viruses seem able to cause
      thrombocytopenia. The advent of molecular techniques has revealed the possible
      persistence of hepatitis B virus genome in HBsAg-negative individuals with or
      without serologic markers of previous infection. This form of infection is named
      occult. We report a case of autoimmune thrombocytopenia associated with acute
      reverse seroconversion of hepatitis B in a patient who was initially hepatitis B
      virus surface antigen negative and hepatitis B virus surface antibody positive.
      The search for occult HBV infection before immunosuppressive therapy and
      monitoring for reactivation is today diagnostic standard and several reports have
      been presented in literature about HBV reactivation following immunosuppressive
      therapy. In our patient, reactivation of dormant HBV happened prior to any
      immunosuppressive therapy. The case we report offers the occasion to emphasize
      the importance of medium-term and long-term hemovigilance also in other kind of
      patients than in subjects on immunosuppressive therapy. A deeper follow-up is
      advisable even in patients showing an unexplainable worsening of their
      hematological conditions.

PMID- 19771536
TI  - p53 codon 72 polymorphism and risk of cervical carcinoma in Moroccan women.
AB  - Human papillomavirus (HPV) has been implicated in cervical carcinoma and the p53
      gene is polymorphic at amino acid 72 of the protein that it encodes. The
      association between p53 polymorphisms and risk for HPV-associated cervical cancer
      has been examined, but the results have been conflicting. It has been reported
      that patients with the arginine form have a higher risk of developing cervical
      cancer than those with the proline form. The purpose of this study was to examine
      whether p53 Arg at the polymorphic position 72 could represents a risk factor for
      women with high-risk HPV-associated malignant cervical lesions. In this study,
      the polymorphism was examined by both allele-specific PCR and RFLP analysis in
      113 patients with cervical cancer and in 100 healthy controls. There was no
      statistical difference in the subtype distribution between the cervix cancer and
      the control groups. There was no significant association between genotype
      distribution of the p53 codon 72 polymorphism and HPV infection. Thus,
      polymorphism of the p53 itself as well as in combination with HPV infection may
      not be a genetic risk for cervical cancer and therefore much attention should be
      paid to other risk factors such as sexual behavior and smoking.

PMID- 19771537
TI  - [Lack of insight into illness of schizophrenia patients from their relatives'
      perspective].
AB  - OBJECTIVE: Lack of insight into illness of patients with schizophrenia is often a
      big problem for relatives. Therefore, information was collected on how relatives
      assess the patients' insight into illness and their current treatment situation.
      This assessment was compared with the relatives' feelings of well-being. METHODS:
      Questionnaire-assisted exploration of 84 relatives, who participated in an
      information session about lack of insight into illness. RESULTS: 73 % of patients
      had a lack of insight into illness according to their relatives. Of these, 79 %
      were male, the mean duration of inpatient treatment was 12 months, 56 % used an
      antipsychotic medication and 80 % were "quite/very ill". Of the patients with
      insight into illness, 45 % were male (p < 0.01), the duration of inpatient
      treatment was significantly longer (29 months; p < 0.05), 86 % used
      antipsychotics (p < 0.05) and only 42 % were judged as "quite/very ill" (p <
      0.01). Only 49 % of relatives from the first group, but 67 % of relatives from
      the second group described their feelings of well-being as "very good / good" (p
      < 0.05). CONCLUSIONS: The lack of insight into illness requires greater
      scientific attention in order to develop better treatment options along with
      greater relief for relatives.

PMID- 19771538
TI  - [Current status of inpatient treatment for borderline personality disorders in
      Germany].
AB  - OBJECTIVES: This study ties in with a former study by Dulz et al. assessing
      inpatient treatment for BPD in Germany and the implementation level of specific
      psychotherapy approaches. METHODS: Via questionnaire we assessed the inpatient
      treatment of BPD. RESULTS: Two hundred and ten out of 817 clinics returned the
      questionnaire (26 %). Nearly all offer BPD treatment. The developments since 1998
      have been shorter inpatient stays and amplified implementation of cognitive
      behavioral therapy, in particular DBT. CONCLUSIONS: During the last 10 years, the
      proportion of clinics with BPD-specific treatments increased markedly.
      Limitations of the study are discussed.

PMID- 19771539
TI  - An in vivo evaluation of surface polishing of TAN intermedullary nails for ease
      of removal.
AB  - Fractures of the tibia and femoral diaphysis are commonly repaired by intra
      medullary (IM) nailing. Currently IM nails are available in either
      electropolished stainless steel (SS) or in Titanium-Aluminium-Niobium (TAN).
      After healing, removal of the nails still is common but removal of TAN IM nails
      often has complications whereas SS IM nails of the same design are less often
      associated with problems. We believe the differences in removal are due to the
      ability of TAN to promote strong bone on-growth. We have previously shown in vivo
      that polishing cortical screws reduces removal torque and the percentage of bone
      implant contact. Therefore, we postulate that bony on-growth onto IM nails can be
      reduced by means of surface polishing, for ease of removal. Here we aim to
      compare the pull-out forces for removal of standard TAN (TAN-S) compared to
      experimental paste polished TAN (TAN-PP) IM nails from a bilateral non-fracture
      sheep tibia model after 12 months implantation. Histological analysis was also
      performed to assess tissue on-growth to the nails. We show that polishing
      significantly reduces (p=0.05) the extraction force required for TAN IM nail
      removal. This effect in part is attributable to the distinct tissue-material
      reaction produced. For TAN-S nails direct bone contact was observed while for TAN
      PP nails a fibrous tissue interface was noted. Since TAN is preferred over SS for
      IM nailing due to superior biocompatibility and mechanical properties, we believe
      these findings could be used to recommend changes to current surface technologies
      of intramedullary nails to reduce complications seen with nail removal especially
      in rapidly growing bone in children.

PMID- 19771540
TI  - The application of bespoke spending functions in group-sequential designs and the
      effect of delayed treatment switching in survival trials.
AB  - For a group-sequential trial with two pre-planned analyses, stopping boundaries
      can be calculated using a simple SAS programme on the basis of the asymptotic
      bivariate normality of the interim and final test statistics. Given the
      simplicity and transparency of this approach, it is appropriate for researchers
      to apply their own bespoke spending function as long as the rate of alpha spend
      is pre-specified. One such application could be an oncology trial where
      progression free survival (PFS) is the primary endpoint and overall survival (OS)
      is also assessed, both at the same time as the analysis of PFS and also later
      following further patient follow-up. In many circumstances it is likely, if PFS
      is significantly extended, that the protocol will be amended to allow patients in
      the control arm to start receiving the experimental regimen. Such an eventuality
      is likely to result in the diminution of any effect on OS. It is shown that
      spending a greater proportion of alpha at the first analysis of OS, using either
      Pocock or bespoke boundaries, will maintain and in some cases result in greater
      power given a fixed number of events.

PMID- 19771541
TI  - Combating plant diseases--the Darwin connection.
AB  - Although Darwin knew of plant diseases, he did not study them as part of his
      analysis of natural selection. Effective plant disease control has only been
      developed after his death. This article explores the relevance of Darwin's ideas
      to three problem areas with respect to diseases caused by fungi: emergence of new
      diseases, loss of disease resistance bred into plants and development of
      fungicide resistance. Darwin's concept of change through natural or artificial
      selection relied on selection of many small changes, but subsequent genetic
      research has shown that change can also occur through large steps. Appearance of
      new diseases can involve gene duplication, transfer or recombination, but all
      evidence points to both host plant resistance and fungicide susceptibility being
      overcome through point mutations. Because the population size of diseases such as
      rusts and powdery and downy mildews is so large, all possible point mutations are
      likely to occur daily, even during moderate epidemics. Overcoming control
      measures therefore reflects the overall fitness of these mutants, and much
      resource effort is being directed towards assessment of their fitness, both in
      the presence and in the absence of selection. While recent developments in
      comparative genomics have caused some revision of Darwin's ideas, experience in
      managing plant disease control measures clearly demonstrates the relevance of
      concepts he introduced 150 years ago. It also reveals the remarkable speed and
      the practical impact of adaptation in wild microorganism populations to changes
      in their environment, and the difficulty of stopping or delaying such adaptation.

PMID- 19771542
TI  - Off-label drug use on a Dutch geriatric ward.

PMID- 19771543
TI  - Poly(ethylene glycol)-block-poly(glycidyl methacrylate) with oligoamine side
      chains as efficient gene vectors.
AB  - Well-defined diblock copolymers, poly(ethylene glycol)-block-poly(glycidyl
      methacrylate)s (PEG-b-PGMAs), with different poly(glycidyl methacrylate) (PGMA)
      chains, were prepared via atom transfer radical polymerization (ATRP) from the
      same macromolecular initiator 2-bromoisobutyryl-terminated poly(ethylene glycol)
      (PEG). Ethyldiamine (EDA), diethylenetriamine (DETA), triethylenetetramine
      (TETA), and polyethyleneimine (PEI) with an M(W) of 400 (PEI(400)) were used to
      decorate PEG-b-PGMAs to get the cationic polymers PEG-b-PGMA- oligoamines. These
      cationic polymers possessed high buffer capability and could condense plasmid DNA
      (pDNA) into nanoscaled complexes of 125-530 nm. These complexes showed the
      positive zeta potential of 20-35 mV at N/P ratios of 10-50. Most of them
      exhibited very low cytotoxicity and good transfection efficiency in 293T cells.
      The presence of the serum medium did not decrease the transfection efficiency due
      to the steric stabilization of the PEG chains.

PMID- 19771544
TI  - Extracellular matrix expression of human prolapsed vaginal wall.
AB  - OBJECTIVE: To compare the mRNA expression of extracellular matrix (ECM) proteins
      in postmenopausal prolapsed versus non-prolapsed anterior vaginal wall (AVW)
      tissue. We hypothesized that the weakening of the tissue leading to prolapse was
      due to decreased collagen production from a downregulation at the transcriptional
      level. METHODS: Following IRB approval, full thickness samples of redundant AVW
      were excised from consecutive age-equivalent, postmenopausal, women undergoing
      cystocele repair (prolapse, stage III or IV), or radical cystectomy (control, no
      clinical findings of prolapse). Total RNA was isolated, cDNA was synthesized, and
      quantitative real-time polymerase chain reaction (PCR) was conducted to assess
      the mRNA expression of collagens type I and III, pro-elastin, MMP3, MMP10, and
      MMP11. The significance of the difference of mRNA expression between prolapse and
      control tissues was tested using Student's t-test followed by Mann-Whitney Rank
      Sum Test. RESULTS: A 5.3-fold increase in collagen type I mRNA was found in
      prolapse (n = 47) over control (n = 7) tissues (P = 0.009). Type III collagen
      mRNA was also significantly increased to a 3.3 times higher level (P = 0.017).
      The ratio of type III to type I was decreased from 15.6 in controls to 9.7 in
      prolapse. An increasing trend in pro-elastin and MMP mRNA expression was found in
      prolapse, but this was not statistically significant. CONCLUSION: In this
      controlled study, the increase found in collagen mRNA expression disproved our
      hypothesis. To the contrary, this defective prolapsed tissue can signal its need
      for ECM replenishment. The message, however, is not being effectively translated
      to assist in tissue remodeling.

PMID- 19771545
TI  - Challenges in developing endpoints for type 1 diabetes intervention studies.
AB  - Development of efficient and safe intervention strategies for preserving and/or
      restoring endogenous insulin production in type 1 diabetes has encountered a wide
      range of challenges, including lack of standardized trial protocols and of
      consensus on appropriate efficacy endpoints. For the greatest part, difficulties
      resided in choosing the most suitable assay(s) and parameter(s) to assess the
      beta-cell function. It is now an accepted approach to evaluate endogenous insulin
      secretion by measuring C-peptide levels (with highly sensitive and normalized
      measurement methods) in response to a physiologic stimulus (liquid mixed-meal)
      under standardized conditions. Preventive interventions mandate the
      identification of well-defined, reliable and validated mechanistic or
      immunological markers of efficacy that would correlate with (and predict) the
      clinical outcome. This has not been consistently achieved to date. However, it
      has been generally agreed that for preventive studies performed very early in the
      disease course (in subjects without signs of autoimmunity against beta-cells)
      development of two or more islet related autoantibodies could be employed as
      biomarkers of disease and thereafter, diagnostic criteria of diabetes serve as
      suitable endpoints.This report summarizes the conclusions of the D-Cure workshop
      of international experts held in Barcelona in April 2007 and the current
      recommendations and updates in the field.

PMID- 19771546
TI  - Comparing performances of logistic regression and neural networks for predicting
      melatonin excretion patterns in the rat exposed to ELF magnetic fields.
AB  - Various studies have been reported on the bioeffects of magnetic field exposure;
      however, no consensus or guideline is available for experimental designs relating
      to exposure conditions as yet. In this study, logistic regression (LR) and
      artificial neural networks (ANNs) were used in order to analyze and predict the
      melatonin excretion patterns in the rat exposed to extremely low frequency
      magnetic fields (ELF-MF). Subsequently, on a database containing 33 experiments,
      performances of LR and ANNs were compared through resubstitution and jackknife
      tests. Predictor variables were more effective parameters and included frequency,
      polarization, exposure duration, and strength of magnetic fields. Also, five
      performance measures including accuracy, sensitivity, specificity, Matthew's
      Correlation Coefficient (MCC) and normalized percentage, better than random (S)
      were used to evaluate the performance of models. The LR as a conventional model
      obtained poor prediction performance. Nonetheless, LR distinguished the duration
      of magnetic fields as a statistically significant parameter. Also, horizontal
      polarization of magnetic fields with the highest logit coefficient (or parameter
      estimate) with negative sign was found to be the strongest indicator for
      experimental designs relating to exposure conditions. This means that each
      experiment with horizontal polarization of magnetic fields has a higher
      probability to result in "not changed melatonin level" pattern. On the other
      hand, ANNs, a more powerful model which has not been introduced in predicting
      melatonin excretion patterns in the rat exposed to ELF-MF, showed high
      performance measure values and higher reliability, especially obtaining 0.55
      value of MCC through jackknife tests. Obtained results showed that such predictor
      models are promising and may play a useful role in defining guidelines for
      experimental designs relating to exposure conditions. In conclusion, analysis of
      the bioelectromagnetic data could result in finding a relationship between
      electromagnetic fields and different biological processes.

PMID- 19771547
TI  - No effects of mobile phone use on cortical auditory change-detection in children:
      an ERP study.
AB  - We investigated the effect of mobile phone use on the auditory sensory memory in
      children. Auditory event-related potentials (ERPs), P1, N2, mismatch negativity
      (MMN), and P3a, were recorded from 17 children, aged 11-12 years, in the recently
      developed multi-feature paradigm. This paradigm allows one to determine the
      neural change-detection profile consisting of several different types of acoustic
      changes. During the recording, an ordinary GSM (Global System for Mobile
      Communications) mobile phone emitting 902 MHz (pulsed at 217 Hz) electromagnetic
      field (EMF) was placed on the ear, over the left or right temporal area (SAR(1g)
      = 1.14 W/kg, SAR(10g) = 0.82 W/kg, peak value = 1.21 W/kg). The EMF was either on
      or off in a single-blind manner. We found that a short exposure (two 6 min blocks
      for each side) to mobile phone EMF has no statistically significant effects on
      the neural change-detection profile measured with the MMN. Furthermore, the multi
      feature paradigm was shown to be well suited for studies of perception accuracy
      and sensory memory in children. However, it should be noted that the present
      study only had sufficient statistical power to detect a large effect size.

PMID- 19771548
TI  - Millimeter wave effects on electrical responses of the sural nerve in vivo.
AB  - Millimeter wave (MMW, 42.25 GHz)-induced changes in electrical activity of the
      murine sural nerve were studied in vivo using external electrode recordings. MMW
      were applied to the receptive field of the sural nerve in the hind paw. We found
      two types of responses of the sural nerve to MMW exposure. First, MMW exposure at
      the incident power density >/=45 mW/cm(2) inhibited the spontaneous electrical
      activity. Exposure with lower intensities (10-30 mW/cm(2)) produced no detectable
      changes in the firing rate. Second, the nerve responded to the cessation of MMW
      exposure with a transient increase in the firing rate. The effect lasted 20-40 s.
      The threshold intensity for this effect was 160 mW/cm(2). Radiant heat exposure
      reproduced only the inhibitory effect of MMW but not the transient excitatory
      response. Depletion of mast cells by compound 48/80 eliminated the transient
      response of the nerve. It was suggested that the cold sensitive fibers were
      responsible for the inhibitory effect of MMW and radiant heat exposures. However,
      the receptors and mechanisms involved in inducing the transient response to MMW
      exposure are not clear. The hypothesis of mast cell involvement was discussed.

PMID- 19771549
TI  - Characteristics of teens with and without work permits.
AB  - BACKGROUND: Factors associated with the issuance of mandated work permits for
      teens, and their enforcement are currently unknown. METHODS: A cross-sectional
      survey was administered to 1945 teens at 16 randomly selected North Carolina high
      schools. Predictor variables examined included teens' socio-demographic
      characteristics, employment patterns, and labor law knowledge. RESULTS: One
      thousand and ninety-four non-working and 844 working teens participated. Seventy
      seven percent of working teens worked during the school year and 39% started
      working younger than 16. The majority (80%) worked in retail and services. Forty
      four percent worked without work permits. Factors associated with being less
      likely to be issued a work permit included white race, employment in a family
      owned business, being a laborer, and limited or no knowledge of child labor laws.
      CONCLUSIONS: Adherence to and enforcement of the work permit system is low.
      Interventions should specifically target teens who work in family owned
      businesses, in unskilled labor and in hazardous industries.

PMID- 19771550
TI  - Hair cortisol predicts object permanence performance in infant rhesus macaques
      (Macaca mulatta).
AB  - Although high circulating levels of glucocorticoids are associated with impaired
      cognitive performance in adults, less is known about this relationship in
      infancy. Furthermore, because studies have relied on acute cortisol measures in
      blood plasma or saliva, interpretation of the results may be difficult as acute
      measures may in part reflect emotional responses to testing procedures. In this
      study we examined whether hair cortisol, an integrated measure of hypothalamic
      pituitary-adrenal (HPA) axis functioning, predicted performance of nursery-reared
      (NR) infant rhesus monkeys (n = 32) on Piagetian object permanence tasks. Testing
      of NR infants began at 19.8 +/- 2.2 (mean +/- SE) days of age and continued for
      the next several months. Hair cortisol concentrations from the 32 NR monkeys were
      compared to those of 20 mother-peer-reared (MPR) infants. Hair was shaved at Day
      14, allowed to regrow, and obtained again at month 6, thus representing
      integrated cortisol over a 5.5-month period of time. NR and MPR infants did not
      differ in month 6 hair cortisol values (t((50)) = 0.02, p = 0.98). Linear
      regression revealed that hair cortisol predicted object permanence performance in
      the NR infants. Infants with higher hair cortisol reached criterion at later ages
      on the well (p < 0.01), screen (p < 0.05), and A-not-B (p < 0.05) tasks and
      required more test sessions to complete the well (p < 0.01) and screen tasks (p <
      0.05). These data are the first to implicate hair cortisol as a reliable
      predictor of early cognitive performance in infant macaque monkeys.

PMID- 19771551
TI  - "Assessment of Multiple Ordinal Endpoints" by L. Haberle, A. Pfahlberg and O.
      Gefeller: biometrical journal (2009) 51, 217-226 article.

PMID- 19771552
TI  - Proteomic differential display analysis identified upregulated astrocytic
      phosphoprotein PEA-15 in human malignant pleural mesothelioma cell lines.
AB  - We performed proteomic differential display analysis of human malignant pleural
      mesothelioma (MPM) cell lines and a human pleural mesothelial cell line by using
      2-DE and LC-MS/MS. The human MPM cell lines were NCI-H28, NCI-H2052 and NCI
      H2452, and the human pleural mesothelial cell line was MeT-5A. Between MeT-5A and
      NCI-H2052, we found 38 protein spots whose expression levels were different, from
      the results of 2-DE; 28 protein spots appeared higher, and 10 other protein spots
      lower in NCI-H2052 than in MeT-5A. These spots were analyzed by LC-MS/MS analysis
      and identified by a peptide sequence tag. However, from the results of 2-DE of
      the other cell lines, there was only one consistently upregulated protein,
      astrocytic phosphoprotein PEA-15, in all three MPM cell lines. Western blotting
      using specific antibodies against PEA-15 confirmed the elevated expression level
      of PEA-15 in all three MPM cell lines compared with MeT-5A cells and normal
      pleura tissues from patients. PEA-15 was knocked down in NCI-H2052 cells, and the
      proliferation of PEA-15-silenced NCI-H2052 cells was suppressed 7-15% compared
      with negative control cells. These results suggest that PEA-15 expression is
      likely to be associated with the tumorigenesis of MPM.

PMID- 19771553
TI  - Elucidation of the percutaneous absorption of chromium compounds by functional
      proteomics.
AB  - Chromium compounds are known to be associated with cytotoxicity and
      carcinogenicity when applied via a skin route. The aim of this study was to
      evaluate the skin permeability and toxicological profiles of four chromium
      species. Chromium permeation across the skin, as determined by an in vitro Franz
      cell, decreased in the order of sodium chromate>potassium chromate>potassium
      dichromate>chromium nitrate. The uptake of chromium species within the skin
      generally showed a contrary trend to the results of permeation, although
      differences among the various compounds were not large. Levels of in vivo skin
      deposition of the four compounds showed no statistically significant differences.
      Potassium chromate produced the greatest disruption of the skin structure as
      determined by HE staining, followed in order by sodium chromate, potassium
      dichromate, and chromium nitrate. This indicates that hexavalent chromium
      elicited greater toxicity to the skin compared to trivalent chromium. A similar
      result was observed for the viability of skin fibroblasts. To improve our
      understanding of the molecular mechanisms leading to functional changes in
      proteins, proteomic tools, including 2-DE and MS techniques combined with
      sequence database correlations, were applied to identify target proteins altered
      by pathologic states. Eight protein spots, corresponding to cutaneous enzymes
      involved in energy metabolism and chaperon proteins, which were identified and
      discussed in this study, were associated with skin cytotoxicity, immunity, and
      carcinogenesis. In addition, functional proteomics of skin tissues may provide a
      promising tool for developing therapeutic strategies and can serve as the basis
      for further research.

PMID- 19771554
TI  - The Karlson Lecture. Phytoecdysteroids: what use are they?
AB  - Phytoecdysteroids are analogues of arthropod steroid hormones found in plants,
      where they deter predation by non-adapted predators. There is potential to
      exploit this to develop new strategies for pest control, either by using
      ecdysteroids as lead molecules for the design of novel pest control agents or by
      alteration of ecdysteroid levels/profiles in crop plants through plant breeding
      or genetic modification. However, it is other properties of phytoecdysteroids
      that have led to a rapid recent increase in scientific and commercial interest in
      these molecules. They are apparently non-toxic to mammals and a wide range of
      beneficial pharmacological (adaptogenic, anabolic, anti-diabetic,
      hepatoprotective, immunoprotective, wound-healing, and perhaps even anti-tumour)
      activities is claimed for them. In particular, this has led to a large (and
      unregulated) market for ecdysteroid-containing preparations for body-builders,
      sportsmen, and pets, among others. Ecdysteroids are also being considered as
      nutraceutical additives to food products. Further, ecdysteroids are good
      candidates as elicitors for gene-switch systems to be used in medical gene
      therapy and research applications. In this article, I review the applications of
      phytoecdysteroids and assess their future potential.

PMID- 19771555
TI  - Detection and identification of 4-hydroxy-2-nonenal Schiff-base adducts along
      with products of Michael addition using data-dependent neutral loss-driven MS3
      acquisition: method evaluation through an in vitro study on cytochrome c oxidase
      modifications.
AB  - We report a data-dependent neutral-loss-driven MS(3) acquisition to enhance, in
      addition to abundant Michael adducts, the detection of Schiff-base adducts of
      proteins and 4-hydroxy-2-nonenal, a reactive end product of lipid peroxidation.
      In vitro modification of cytochrome c oxidase, a mitochondrial protein complex,
      was used as a model to evaluate the method. The technique allowed for a confident
      validation of modification sites and also identified a Schiff-base adduct in
      subunit Vb of the protein complex.

PMID- 19771556
TI  - A new approach to monitor expression of aldo-keto reductase proteins in mouse
      tissues.
AB  - The aldo-keto reductase (AKR) proteins catalyze reduction of diverse aldehydes
      and play detoxification roles in many organisms. Since many substrates are shared
      among AKR, it is generally accepted that these enzymes can functionally
      compensate each other in response to oxidative stress. Their overall abundances
      are the important factor that partially reflects the capacity of antioxidant and
      detoxification in tissues. In this study, the strategy was proposed for
      generation of Pan-AKR antibodies to recognize most AKR proteins in mouse tissues.
      Derived from bioinformatic analysis, several consensus peptides with different
      potential antigenicities were synthesized, conjugated to hemocyanin from keyhole
      limpets and further delivered to rabbits to generate polyclonal antibodies. Three
      Pan-AKR antibodies exhibited the immune specificities and immune sensitivities,
      Pan-AKR-P1 for AKR1B and AKR1C, Pan-AKR-P3 for AKR1C and Pan-AKR-P4 for all the
      AKR proteins. Pan-AKR-P4 antibody was employed to 2-DE Western blot to examine
      the AKR abundances in mouse liver and kidney, resulting in seven immune-reactive
      spots from each tissue. Protein identification with MS revealed that most immune
      positive spots were the members of AKR superfamily. Furthermore, Pan-AKR-P4
      antibody was implemented to compare the different abundances of the AKR proteins
      in liver and kidney between normal and diabetic mice, suggesting that diabetes
      did cause some abnormal changes in the AKR protein abundances.

PMID- 19771557
TI  - Comparative analysis of OFFGel, strong cation exchange with pH gradient, and RP
      at high pH for first-dimensional separation of peptides from a membrane-enriched
      protein fraction.
AB  - The analysis and quantitation of membrane proteins have proved challenging for
      proteomics. Although several approaches have been introduced to complement gel
      based analysis of intact proteins, the literature is rather limited in comparing
      major emerging approaches. Peptide fractionation using IEF (OFFGel), strong
      cation exchange HPLC using a pH gradient (SCX-pG), and RP HPLC at high pH, have
      been shown to increase peptide and protein identification over classic MudPIT
      approaches. This article compares these three approaches for first-dimensional
      separation of peptides using a detergent phase (Triton X-114) enriched membrane
      fraction from mouse cortical brain tissue. Results indicate that RP at high pH
      (pH 10) was superior for the identification of more peptides and proteins in
      comparison to the OFFGel or the SCX-pG approaches. In addition, gene ontology
      analysis (GOMiner) revealed that RP at high pH (pH 10) successfully identified an
      increased number of proteins with "membrane" ontology, further confirming its
      suitability for membrane protein analysis, in comparison to SCX-pG and OFFGel
      techniques.

PMID- 19771559
TI  - Localized network centrality and essentiality in the yeast-protein interaction
      network.
AB  - It has been suggested that a close relationship exists between gene essentiality
      and network centrality in protein-protein interaction networks. However, recent
      studies have reported somewhat conflicting results on this relationship. In this
      study, we investigated whether essential proteins could be inferred from network
      centrality alone. In addition, we determined which centrality measures describe
      the essentiality well. For this analysis, we devised new local centrality
      measures based on several well-known centrality measures to more precisely
      describe the connection between network topology and essentiality. We examined
      two recent yeast protein-protein interaction networks using 40 different
      centrality measures. We discovered a close relationship between the path-based
      localized information centrality and gene essentiality, which suggested
      underlying topological features that represent essentiality. We propose that two
      important features of the localized information centrality (proper representation
      of environmental complexity and the consideration of local sub-networks) are the
      key factors that reveal essentiality. In addition, a random forest classifier
      showed reasonable performance at classifying essential proteins. Finally, the
      results of clustering analysis using centrality measures indicate that some
      network clusters are closely related with both particular biological processes
      and essentiality, suggesting that functionally related proteins tend to share
      similar network properties.

PMID- 19771560
TI  - Control of the release of digestive enzymes in the larvae of the fall armyworm,
      Spodoptera frugiperda.
AB  - There is a basal level of enzyme activity for trypsin, aminopeptidase, amylase,
      and lipase in the gut of unfed larval (L6) Spodoptera frugiperda. Trypsin
      activity does not decrease with non-feeding, possibly because of the low protein
      levels in plants along with high amino acid requirements for growth and storage
      (for later reproduction in adults). Therefore, trypsin must always be present so
      that only a minimal protein loss via egestion occurs. Larvae, however, adjust
      amylase activity to carbohydrate ingestion, and indeed amylase activity is five
      fold higher in fed larvae compared to unfed larvae. Gut lipase activity is low,
      typical of insects with a high carbohydrate diet. A flat-sheet preparation of the
      ventriculus was used to measure the release of enzymes in response to specific
      nutrients and known brain/gut hormones in S. frugiperda. Sugars greatly increase
      (>300%) amylase release, but starch has no effect. Proteins and amino acids have
      little or no effect on trypsin or aminopeptidase release. The control of enzyme
      release in response to food is likely mediated through neurohormones. Indeed, an
      allatostatin (Spofr-AS A5) inhibits amylase and trypsin, and allatotropin (Manse-
      AT) stimulates amylase and trypsin release. Spofr-AS A5 also inhibits ileum
      myoactivity and Manse-AT stimulates myoactivity. The epithelial secretion rate of
      amylase and trypsin was about 20% of the amount of enzyme present in the
      ventricular lumen, which, considering the efficient counter-current recycling of
      enzymes, suggests that the secretion rate is adequate to replace egested enzymes.

PMID- 19771558
TI  - Interactions of the NPXY microdomains of the low density lipoprotein receptor
      related protein 1.
AB  - The low density lipoprotein receptor-related protein 1 (LRP1) mediates
      internalization of a large number of proteins and protein-lipid complexes and is
      widely implicated in Alzheimer's disease. The cytoplasmic domain of LRP1 (LRP1
      CT) can be phosphorylated by activated protein-tyrosine kinases at two NPXY
      motifs in LRP1-CT; Tyr 4507 is readily phosphorylated and must be phosphorylated
      before phosphorylation of Tyr 4473 occurs. Pull-down experiments from brain
      lysate revealed numerous proteins binding to LRP1-CT, but the results were highly
      variable. To separate which proteins bind to each NPXY motif and their
      phosphorylation dependence, each NPXY motif microdomain was prepared in both
      phosphorylated and non-phosphorylated forms and used to probe rodent brain
      extracts for binding proteins. Proteins that bound specifically to the
      microdomains were identified by LC-MS/MS, and confirmed by Western blot.
      Recombinant proteins were then tested for binding to each NPXY motif. The
      NPXY(4507) (membrane distal) was found to interact with a large number of
      proteins, many of which only bound the tyrosine-phosphorylated form. This
      microdomain also bound a significant number of other proteins in the
      unphosphorylated state. Many of the interactions were later confirmed to be
      direct with recombinant proteins. The NPXY(4473) (membrane proximal) bound many
      fewer proteins and only to the phosphorylated form.

PMID- 19771561
TI  - Resected colorectal liver metastases: does the survival differ according to
      postoperative chemotherapy regimen?
AB  - BACKGROUND AND OBJECTIVES: We compared clinical outcomes in patients who were
      treated with different chemotherapeutic regimens after resection of hepatic
      metastases from colorectal cancer (CRC). METHODS: Between August 2001 and June
      2008, 156 patients who entered into chemotherapy of adjuvant intent after hepatic
      metastasectomy were reviewed retrospectively. RESULTS: Of the 156 patients, 58
      patients were treated with oxaliplatin/fluoropyrimidines (group I), 48 with
      irinotecan/fluoropyrimidines (group II), and 50 with fluoropyrimidines alone
      (group III). In the univariate analysis, there was a marginally significant
      difference among the three groups with respect to the disease-free survival
      (DFS); 23.4 months in group I, 14.1 months in group II, and 16.3 months in group
      III, P = 0.088). Group I showed better DFS when compared to the other two groups
      combined (group II and III) (P = 0.03). Multivariable analysis showed a
      marginally significant gain in the DFS for group I (P = 0.068). Multiple
      metastases (P = 0.045) and positive resection margin (P = 0.003) were
      significantly associated with poorer DFS. CONCLUSION: Postoperative combination
      chemotherapy of oxaliplatin/fluoropyrimidines seemed to show better DFS when
      compared to fluoropyrimidine monotherapy or irinotecan-based combination in
      patients who underwent liver metastasectomy.

PMID- 19771562
TI  - Recent progress in understanding the pathology of malignant melanoma.
AB  - Recently, several important findings on melanoma development and progression have
      accelerated progress towards a molecular understanding of melanoma biology.
      Furthermore, the development of experimental tools, such as a wide range of cell
      lines and animal models of metastasis, has turned melanoma into a model for
      general tumour research. However, it has also become evident that melanoma is
      distinct from other tumours with regard to its cellular origin and
      pathophysiological mechanisms. This review focuses on important new findings that
      have contributed to a greater understanding of the molecular processes leading to
      melanoma. Translating these innovative new results into potent therapeutic
      approaches will require even more effort.

PMID- 19771563
TI  - Mammographic casting-type calcifications is not a prognostic factor in unifocal
      small invasive breast cancer: a population-based retrospective cohort study.
AB  - BACKGROUND AND OBJECTIVES: The role of mammographic casting-type
      microcalcifications as a prognostic factor in breast cancer has been debated. We
      studied the relation between mammographic features and prognosis in a population
      based cohort. METHODS: In 515 women with 1-15 mm invasive breast cancer
      mammograms were re-classified according to Tabar et al. The relation to breast
      cancer death was studied. RESULTS: During the follow-up (median 155 months) 44 of
      515 women died from breast cancer. Twenty-nine of 515 presented with casting-type
      calcifications and three of these died from breast cancer. The adjusted odds
      ratio for breast cancer death was 1.6 (0.5-5.8) for patients presenting with
      casting-type calcifications and 4.8 (1.8-12.7) for crushed stone-like
      (pleomorphic) calcifications using stellate tumors as a reference group.
      CONCLUSIONS: Except for patients with crushed stone-like microcalcifications
      breast cancer survival was excellent, 87-95% after 15 years. Casting-type
      calcifications were not a statistically significant prognostic factor. Tumors
      with casting-type calcifications were more often of high grade, hormone receptor
      negative, and HER2 positive but this was not statistically significant either.
      However, microcalcifications may be more prevalent in tumors with extensive
      ductal cancer in situ (DCIS) containing multiple foci of invasive cancer and in
      this study we only included unifocal cancer.

PMID- 19771564
TI  - Fibril protein fragmentation pattern in systemic AL-amyloidosis.
AB  - Immunoglobulin light chain (AL)-amyloidosis was one of the first types of
      amyloidosis discovered and still little is known about its pathogenic mechanisms.
      One major obstacle is the very heterogeneous condition; in fact, every patient
      could be considered to have their own disease since symptoms and outcome vary
      enormously. The reason for this is not known but intrinsic factors of the
      immunoglobulin light chain (LC) and the fact that every LC is unique seem to be
      important. Post-translational modifications such as glycosylation and proteolysis
      are most certainly involved. By using western blotting, we studied in detail the
      proteolytic pattern in six patients with AL-amyloidosis of kappa type with the
      aid of three peptide antisera against two domains in the constant segment and one
      conserved domain in framework 3 of the variable region. Materials from one to
      five organs were analysed. The result clearly demonstrates that the fragmentation
      pattern was similar in amyloid of different organs in one patient but differed
      greatly between patients. Full-length, N-, and C-terminal fragments were detected
      with the three antisera. The results strongly support the hypothesis that
      proteolytic cleavage occurs after fibril formation.

PMID- 19771565
TI  - One-dimensional composite nanomaterials: synthesis by electrospinning and their
      applications.
AB  - This Review provides an overview of the synthesis of one-dimensional (1D)
      composite nanomaterials by electrospinning and their applications. After a brief
      description of the development of the electrospinning technique, the
      transformation of an inorganic nanocomponent or polymer into another kind of
      polymer or inorganic matrix is discussed in terms of the electrospinning process,
      including the direct-dispersed method, gas-solid reaction, in situ
      photoreduction, sol-gel method, emulsion electrospinning method, solvent
      evaporation, and coaxial electrospinning. In addition, various applications of
      such 1D composite nanomaterials are highlighted in terms of electronic and
      optical nanodevices, chemical and biological sensors, catalysis and
      electrocatalysis, superhydrophobic surfaces, environment, energy, and biomedical
      fields. An increasing number of investigations show that electrospinning has been
      not only a focus of academic study in the laboratory but is also being applied in
      a great many technological fields.

PMID- 19771566
TI  - Single-walled carbon-nanotube dispersion with electrostatically tethered
      nanoplatelets.

PMID- 19771567
TI  - Mechanofabrication of pancake and rodlike nanostructures from deformable
      nanoparticle aggregates.

PMID- 19771568
TI  - Stabilization of polymer-hydrogel capsules via thiol-disulfide exchange.
AB  - Polymer hydrogels are used in diverse biomedical applications including drug
      delivery and tissue engineering. Among different chemical linkages, the natural
      and reversible thiol-disulfide interconversion is extensively explored to
      stabilize hydrogels. The creation of macro-, micro-, and nanoscale disulfide
      stabilized hydrogels commonly relies on the use of oxidizing agents that may have
      a detrimental effect on encapsulated cargo. Herein an oxidization-free approach
      to create disulfide-stabilized polymer hydrogels via a thiol-disulfide exchange
      reaction is reported. In particular, thiolated poly(methacrylic acid) is used and
      the conditions of polymer crosslinking in solution and on colloidal porous and
      solid microparticles are established. In the latter case, removal of the core
      particles yields stable, hollow, disulfide-crosslinked hydrogel capsules.
      Further, a procedure is developed to achieve efficient disulfide crosslinking of
      multilayered polymer films to obtain stable, liposome-loaded polymer-hydrogel
      capsules that contain functional enzymatic cargo within the liposomal
      subcompartments. This approach is envisaged to facilitate the development of
      biomedical applications of hydrogels, specifically those including fragile cargo.

PMID- 19771569
TI  - Functionalization of silicon nanowires with actomyosin motor protein for
      bioinspired nanomechanical applications.

PMID- 19771570
TI  - Tuning the electrical properties of Si nanowire field-effect transistors by
      molecular engineering.
AB  - Exposed facets of n-type silicon nanowires (Si NWs) fabricated by a top-down
      approach are successfully terminated with different organic functionalities,
      including 1,3-dioxan-2-ethyl, butyl, allyl, and propyl-alcohol, using a two-step
      chlorination/alkylation method. X-ray photoemission spectroscopy and
      spectroscopic ellipsometry establish the bonding and the coverage of these
      molecular layers. Field-effect transistors fabricated from these Si NWs displayed
      characteristics that depended critically on the type of molecular termination.
      Without molecules the source-drain conduction is unable to be turned off by
      negative gate voltages as large as -20 V. Upon adsorption of organic molecules
      there is an observed increase in the "on" current at large positive gate voltages
      and also a reduction, by several orders of magnitude, of the "off" current at
      large negative gate voltages. The zero-gate voltage transconductance of molecule
      terminated Si NW correlates with the type of organic molecule. Adsorption of
      butyl and 1,3-dioxan-2-ethyl molecules improves the channel conductance over that
      of the original SiO(2)-Si NW, while adsorption of molecules with propyl-alcohol
      leads to a reduction. It is shown that a simple assumption based on the possible
      creation of surface states alongside the attachment of molecules may lead to a
      qualitative explanation of these electrical characteristics. The possibility and
      potential implications of modifying semiconductor devices by tuning the
      distribution of surface states via the functionality of attached molecules are
      discussed.

PMID- 19771571
TI  - Unbearable suffering of patients with a request for euthanasia or physician
      assisted suicide: an integrative review.
AB  - PURPOSE: In the legal performance of the euthanasia procedure, unbearable
      suffering, one of the requirements of due care, is difficult to assess.
      Evaluation of the current knowledge of unbearable suffering is needed in the
      ongoing debate about the conditions on which EAS can be approved. METHODS: Using
      an integrative literature review, we evaluated publications with definitions of
      suffering in general or in end-of-life situations and with descriptions of
      suffering in the context of a request for EAS. DATA SYNTHESIS: From the 1482
      citations identified, we included 55 publications: 20 articles about definitions
      of suffering and 35 empirical studies on suffering. We found no definition of
      unbearable suffering in the context of a request for EAS. Qualitative patient
      centered studies revealed the most motivations, and the most motivations named by
      only one of the three parties involved. The studies of relatives were limited,
      mainly quantitative and retrospective. We found no studies that brought together
      the views of the patients, relatives, and healthcare professionals. CONCLUSIONS:
      There is no generally accepted definition of 'unbearable suffering' in the
      context of a request for EAS. On the basis of the articles reviewed, we propose
      the following conceptual definition: 'Unbearable suffering in the context of a
      request for EAS is a profoundly personal experience of an actual or perceived
      impending threat to the integrity or life of the person, which has a significant
      duration and a central place in the person's mind'. Further patient-centered
      qualitative research into suffering is needed to clarify this definition.

PMID- 19771572
TI  - Interaction of 'toxic' and 'immunogenic' A-gliadin peptides with a membrane
      mimetic environment.
AB  - Celiac disease (CD) is characterized by abnormally high concentrations of certain
      peptides in the small bowel. These peptides can be grouped in 'toxic' and
      'immunogenic' classes, which elicit an innate immune response and an HLA-mediated
      adaptive response, respectively. It is not clear on which molecular mechanisms
      responses to these different classes are based, but the 31-43 (P31-43) and the 56
      68 (P56-68) A-gliadin fragments are usually adopted as sequence representatives
      of toxic and immunogenic peptides, respectively. Here we report fluorescence
      experiments aiming to mimic the interaction of these peptides with the cell
      membrane surface by using sodium dodecyl sulphate (SDS) as a membrane-mimetic
      medium. We show that P31-43 is able to bind SDS micelles in a way that resembles
      mixed micelle formation. On the other hand, no binding at all could be detected
      for P56-68. This different behaviour could be related to the paracellular or
      transcellular route through which gluten peptides may cross the intestinal
      epithelium, and open new insights into the pathogenetic mechanisms of CD.

PMID- 19771573
TI  - 'Admission into a helping plan': a watershed between positive and negative
      experiences in breast cancer.
AB  - Cancer patients are in an exposed situation that raises certain psychosocial
      needs in contact with health care. Previous studies have mainly investigated
      these needs by assessments on pre-defined categories. OBJECTIVE: The purpose of
      the present study is, from the patients' perspective, to identify breast cancer
      patients' psychosocial needs, and to synthesise them in a model reflecting the
      core of these needs. METHODS: Seventy-one patients treated with radiation therapy
      were consecutively included and repeatedly interviewed about their experiences of
      health care. 'Critical incidents' where identified from the interviews and
      analysed due to the similarities-differences technique in grounded theory.
      RESULTS: Four categories of needs where detected: 'access', 'information',
      'treatment' and 'how approached'. These categories and their properties merged
      into a core category--'admission into a helping plan'. These findings are well
      understood in terms of attachment theory. In times of imminent danger and stress
      people strive to find a 'safe haven' to attach to. Cancer patients' 'safe haven'
      can be described as 'a helping plan'. It is not the result of a separate patient
      caregiver relationship but is created by a pattern of individual experiences from
      all kind of contacts with the health-care system as a whole. CONCLUSIONS: The
      presented model of patients needs as converging into 'admission into a helping
      plan' may serve as an easily comprehendible model for caregivers, guiding them to
      contribute to the patient's feeling of security and trust, and thus to the
      patient's own 'hope work'.

PMID- 19771574
TI  - Software for generating liability distributions for pedigrees conditional on
      their observed disease states and covariates.
AB  - For many multifactorial diseases, aetiology is poorly understood. A major
      research aim is the identification of disease predictors (environmental,
      biological, and genetic markers). In order to achieve this, a two-stage approach
      is proposed. The initial or synthesis stage combines observed pedigree data with
      previous genetic epidemiological research findings, to produce estimates of
      pedigree members' disease risk and predictions of their disease liability. A
      further analysis stage uses the latter as inputs to look for associations with
      potential disease markers. The incorporation of previous research findings into
      an analysis should lead to power gains. It also allows separate predictions for
      environmental and genetic liabilities to be generated. This should increase power
      for detecting disease predictors that are environmental or genetic in nature.
      Finally, the approach brings pragmatic benefits in terms of data reduction and
      synthesis, improving comprehensibility, and facilitating the use of existing
      statistical genetics tools. In this article we present a statistical model and
      Gibbs sampling approach to generate liability predictions for multifactorial
      disease for the synthesis stage. We have implemented the approach in a software
      program. We apply this program to a specimen disease pedigree, and discuss the
      results produced, comparing its results with those generated under a more naive
      model. We also detail simulation studies that validate the software's operation.

PMID- 19771575
TI  - Clinical factors are not the best predictors of quality of sexual life and sexual
      functioning in women with early stage breast cancer.
AB  - BACKGROUND: Few studies have prospectively assessed the impact of breast cancer
      (BC) on women's sexual lives. Therefore, this study examines the determinants of
      quality of sexual life (QOSL), sexual functioning (SF), and sexual enjoyment (SE)
      at 6 and 12 months after surgical treatment. METHODS: All participants completed
      a measure of QOSL (The World Health Organization Quality of Life assessment
      instrument-100 (WHOQOL-100)-facet Sexual Activity) before diagnosis (Time-1), and
      1 (Time-2), 3 (Time-3), 6 (Time-4) and 12 months (Time-5) after surgical
      treatment. At Time-1, women also completed questionnaires on personality (The
      State Trait Anxiety Inventory-trait, NEO-FFI), body image and self-esteem (WHOQOL
      100), depressive symptoms (Center for Epidemiological Studies-Depression Scale),
      and fatigue (Fatigue Assessment Scale). Furthermore, SF and SE (The European
      Organisation for Research and Treatment of Cancer Quality of Life Questionnaire
      Breast Cancer module) were measured from Time-2 onwards. RESULTS: At baseline,
      the analysis included 223 women with early stage BC. Clinical factors did not
      predict QOSL, SF or SE. In the final analyses, trait anxiety predicted QOSL and
      SF at Time-4 (p's<0.01). At Time-5, agreeableness predicted QOSL and SE
      (p's<0.05). Having a partner and age predicted SF, while SE was predicted by
      educational level (Time-4). In addition, fatigue predicted SE at Time-4 (p<0.05).
      In general, QOSL diminished across time, while SF improved. However, women with a
      mastectomy did not differ from women with breast conserving therapy. CONCLUSIONS:
      Mainly personality and psychological factors affect patients' sexuality after
      surgical treatment. Clinical factors did not predict QOSL, SF or SE. More
      knowledge in this field will help professionals to identify women who are at risk
      of experiencing sexual problems and consequently will contribute to provide
      adequate support.

PMID- 19771580
TI  - Aeration in fermentations. 1961.

PMID- 19771581
TI  - Scoring of collagen organization in healthy and diseased human dermis by
      multiphoton microscopy.
AB  - We have used nonlinear imaging to evaluate collagen organization in connective
      tissue ex-vivo samples. Image analysis methods were tested on healthy dermis,
      normal scars, and keloids. The evaluation of the second harmonic to
      autofluorescence aging index of dermis (SAAID) has allowed a first
      characterization of tissues by scoring the collagen/elastin content. Further
      analyses on collagen morphology in healthy dermis and keloids were performed by
      image-pattern analysis of SHG images. The gray-level co-occurrence matrix (GLCM)
      analysis method has allowed classification of different tissues based on the
      evaluation of geometrical arrangement of collagen fibrillar bundles, whereas a
      pattern analysis of the FFT images has allowed the discrimination of different
      tissues based on the anisotropy of collagen fibers distribution. This multiple
      scoring method represents a promising tool to be extended to other collagen
      disorders, as well as to be used in in-vivo skin-imaging applications.

PMID- 19771582
TI  - Two- and three-dimensional profilometer assessments to determine titanium
      roughness.
AB  - In this study, a comparative topography analysis of titanium (Ti) surfaces was
      performed using two- (2D) and three-dimensional (3D) profilometers. Ti samples
      were either only sandblasted (SB) using Al(2)O(3) particles or were SB and
      received an additional chemical treatment using a solution of 4% HF (SLA).
      Samples with no treatment were used as a control group (C). Therefore, three
      different surfaces were evaluated: SB, SLA and C. The Ti surface topographies
      were evaluated by scanning electron microscopy. An Ra roughness measurement was
      performed on each Ti sample by 2D and 3D profilometers. Surface roughness was
      also characterized using amplitude, spatial and hybrid 3D parameters. 2D and 3D
      profilometer analyses produced very close results. Mean Ra values range from 0.19
      to 0.25 (C, p<0.05), 0.84 to 0.99 (SLA, p<0.05) and 0.98 to 1 microm (SB,
      p>0.05). The statistically different Ra values depending on the surface studied
      may be explained by methodological and technical differences. Also, 3D
      profilometer seems to be the more appropriate analytical method for measuring the
      roughness of Ti surfaces because it also describes surface organization.

PMID- 19771583
TI  - BOLD MRI in sheep fetuses: a non-invasive method for measuring changes in tissue
      oxygenation.
AB  - OBJECTIVE: The purpose of this descriptive study was to correlate changes in the
      blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) signal with
      direct measurements of fetal tissue oxygenation. METHODS: Seven anesthetized ewes
      carrying singleton fetuses at 125 days' gestation (term 145 days) underwent BOLD
      MRI, covering the entire fetus in a multislice approach. The fetuses were
      subjected to normoxic, hypoxic and hyperoxic conditions by changing the
      O(2)/N(2)O ratio in the maternal ventilated gas supply. The partial pressure of
      oxygen (pO2) in the fetal liver was measured using an oxygen-sensitive optode.
      Maternal arterial blood samples were simultaneously withdrawn for blood gas
      analysis. These measurements were compared with BOLD MRI signals in the fetal
      liver, kidney, spleen and brain. RESULTS: We demonstrated a consistent increase
      in the BOLD MRI signal with increasing tissue pO(2). For the fetal liver, spleen
      and kidney we observed a clear association between changes in maternal arterial
      blood pO2 and changes in BOLD MRI signal. Interestingly, we found that the BOLD
      signal of the fetal brain remained unchanged during hypoxic, normoxic and
      hyperoxic conditions. CONCLUSIONS: This experimental study demonstrated that BOLD
      MRI is a reliable non-invasive method for measuring changes in tissue oxygenation
      in fetal sheep. The unchanged signal in the fetal brain during altered maternal
      oxygen conditions is probably explained by the brain-sparing mechanism.

PMID- 19771584
TI  - Binding to dipeptidyl peptidase-4 determines the disposition of linagliptin (BI
      1356)--investigations in DPP-4 deficient and wildtype rats.
AB  - Linagliptin (BI 1356) is a novel dipeptidyl peptidase-4 (DPP-4) inhibitor in
      clinical development for the treatment of type 2 diabetes. It exhibits non-linear
      pharmacokinetics and shows concentration-dependent plasma protein binding to its
      target, DPP-4. The aim of this study was to investigate the impact of saturable
      binding of linagliptin to plasma and tissue DPP-4 by comparing the
      pharmacokinetics of linagliptin in wildtype and DPP-4 deficient Fischer rats
      using non-compartmental and model-based data analysis. The non-compartmental
      analysis revealed a significantly reduced AUC in DPP-4 deficient rats compared
      with wildtype rats when single intravenous doses <or=1 mg/kg were administered,
      but the exposure was similar in both strains at higher doses. The terminal half
      lives were significantly shorter in DPP-4 deficient rats compared with wildtype
      rats. For doses <or=1 mg/kg, DPP-4 deficient rats exhibited linear
      pharmacokinetics, whereas the pharmacokinetics of wildtype rats was non-linear.
      In the model-based analysis these differences could be accounted for by assuming
      concentration-dependent protein binding in the central and one peripheral
      compartment in wildtype rats. In the model, disposition parameters for unbound
      linagliptin were assumed to be identical in both rat strains. Simulations with
      different doses of linagliptin and different concentrations of binding sites
      further illustrated that the interdependence of linagliptin and DPP-4 in plasma
      and in the periphery has a major influence on the disposition of linagliptin in
      wildtype rats. In conclusion, the study showed that the concentration-dependent
      binding of linagliptin to its target DPP-4 has a major impact on the plasma
      pharmacokinetics of linagliptin.

PMID- 19771585
TI  - Laterality in semi-free-ranging black and white ruffed lemurs (Varecia variegata
      variegata): head-tilt correlates with hand use during feeding.
AB  - Previous studies in human and chimpanzee infants have identified a predictive
      relationship between early rightward head orientation and later right hand use.
      Data from lemurs suggest a leftward bias in hand preference, but there are no
      data on head positioning. The purpose of this study was to examine the
      relationship between head and hand preferences in the black and white ruffed
      lemur (Varecia variegata variegata). Ruffed lemurs rotate the head vertically
      during chewing in a behavior called head-tilting. Frequency of head-tilting and
      bouts of unimanual hand use were measured during normal feeding in a semi-free
      ranging population of lemurs. Subjects were provisioned at feeding platforms
      twice daily with fresh fruits, vegetables, and other food items. Sampling was
      spontaneous and all observations were videotaped. No group-level bias was found
      for head-tilting, but a left hand bias emerged for hand use. A positive
      relationship was found between direction of head-tilting preference and direction
      of hand use preference such that left head-tilts increased as left hand use
      increased. Furthermore, left head-tilts increased as the degree of hand
      preference lateralization increased. When the hand used to bring food to the
      mouth just before head-tilting was examined, there was a strong bias for the left
      hand to precede left head-tilts. For right head-tilts, however, lemurs were
      equally likely to use either hand before head-tilting. Overall a strong
      relationship was found between the left hand and left head-tilting in black and
      white ruffed lemurs, suggesting a common link between these behaviors. However,
      the direction of bias was different from that seen in human and chimpanzee
      studies. Additional studies on patterns of laterality would be informative for
      understanding how laterality has changed across the primate order and the
      adaptive significance of laterality in primates.

PMID- 19771586
TI  - Recruitment of hippocampal neurons to encode behavioral events in the rat:
      alterations in cognitive demand and cannabinoid exposure.
AB  - Successful performance by rats of a delayed-nonmatch-to-sample (DNMS) task is
      hippocampal dependent. We have shown that neurons in hippocampus differentially
      encode task-relevant events. These responses are critical for correct DNMS
      performance and are diminished by exogenous cannabinoids. We therefore reasoned
      that hippocampal neural correlates of behavior are likely shaped during learning;
      however, to date, no work has examined these correlates during DNMS acquisition
      training. Consequently, the present study assessed the emergence of hippocampal
      neural encoding when (i) cognitive task demands were increased through
      prolongation of delay intervals between sample and nonmatch phase and (ii) when
      animals are under cannabinoid treatment and performance is compromised. Adult,
      male Long-Evans rats were trained to perform the DNMS task without delay and then
      implanted with multielectrode recording arrays directed to CA3 and CA1 subfields
      of the hippocampus. Following recovery, single units were isolated and animals
      divided into two treatment groups: vehicle or WIN 55,212-2 (WIN-2, 0.35 mg/kg).
      Ensemble firing was monitored during retraining in DNMS task at 0 s, and
      subsequently delay intervals were progressively increased to 1-10 s, 11-20 s, and
      21-30 s when animals met criterion (80% correct) at each respective interval.
      Hippocampal CA3 and CA1 principal cells were isolated and recorded throughout
      treatment. Extension of the delay led to an increase in the number of task
      correlated neurons in controls. This recruitment of novel cells was
      reduced/prevented in the presence of WIN-2 and was paralleled by impairment in
      acquisition learning at longer delay intervals. Moreover, WIN-2 suppressed
      hippocampal ensemble firing during the sample (encoding) but not nonmatch phase
      of the DNMS task across all delays. These cannabinoid-induced alterations in
      hippocampal neuronal activity may explain the observed deficits in DNMS
      performance.

PMID- 19771588
TI  - The EORTC cancer outpatient satisfaction with care questionnaire in ambulatory
      radiotherapy: EORTC OUT-PATSAT35 RT. Validation study for Spanish patients.
AB  - OBJECTIVES: The EORTC OUT-PATSAT35 RT questionnaire evaluates the satisfaction
      with care (SC) expressed by cancer outpatients treated with radiotherapy. In this
      study we assess the psychometric properties of the OUT-PATSAT35 RT when applied
      to a sample of Spanish patients. METHODS: A total of 100 patients with different
      tumor sites completed the EORTC core questionnaire, QLQ-C30, the OUT-PATSAT35 RT,
      the Oberst patients' perception of care quality and satisfaction scale (OS) and
      the item on intention to recommend the hospital (IR). Psychometric evaluation of
      the structure, reliability and validity of the questionnaire was conducted.
      RESULTS: Multitrait-scaling analysis showed that 33 out of 34 item-scale
      correlation coefficients met the standards for convergent validity and that many
      of them met the standards for discriminant validity. Cronbach's coefficients were
      good (0.70-0.97) for all scales except environment. Correlations between the
      areas of the QLQ-C30 and OUT-PATSAT35 RT were generally low (<0.40). Correlations
      between the OS and the IR were moderate with the EORTC OUT-PATSAT35 RT. Areas
      whose contents were more related had higher correlation coefficients (>0.50), and
      vice versa (<0.20). Patients with higher scores on the OS and the IR, patients
      who had more visits to the doctor and patients who had a better performance
      status showed higher SC levels in 12, 8 and 1 OUT-PATSAT35 RT areas,
      respectively. CONCLUSIONS: The OUT-PATSAT35 RT appears to be a reliable and valid
      instrument when applied to a sample of Spanish cancer patients. These results are
      in line with those of the validation study conducted by the authors of the
      questionnaire.

PMID- 19771587
TI  - Environmental influence on L1 retrotransposons in the adult hippocampus.
AB  - It is well established that neuronal circuits can be shaped by experience.
      Neuronal plasticity can be achieved by synaptic competitive interactions and the
      addition of new neuronal units in neurogenic regions of the adult brain. Recent
      data have suggested that neuronal progenitor cells can accommodate somatic LINE-1
      (Long Interspersed Nuclear Elements-1 or L1) retrotransposition. Genomic L1
      insertions may up- or down-regulate transcriptional control of gene expression.
      Here, we show that exercise has a positive effect on a L1-EGFP reporter in vivo.
      We found that neurons from mice that experience voluntary exercise are more
      likely to activate an EGFP reporter marker, representing L1 insertions in the
      brain, when compared with sedentary animals. In the hippocampus, a neurogenic
      region of the adult brain, EGFP expression is mainly found in cells localized in
      the subgranular layer of the dentate gyrus. This observation implies that
      neuronal progenitor cells may support de novo retrotransposition upon exposure to
      a new environment. Such evidence suggests that experience-dependent L1
      retrotransposition may contribute to the physiological consequences of neuronal
      plasticity.

PMID- 19771589
TI  - Postnatal binge-like alcohol exposure decreases dendritic complexity while
      increasing the density of mature spines in mPFC Layer II/III pyramidal neurons.
AB  - Prenatal exposure to alcohol in humans can result in a wide range of deficits
      collectively referred to as fetal alcohol spectrum disorders. Of these deficits,
      cognitive impairments are among the most debilitating and long-lasting.
      Specifically, cognitive impairments in executive functioning suggest damage to
      the prefrontal cortex (PFC). Several external stimuli, such as morphine, chronic
      stress, and maternal stress have been found to alter the dendritic structure of
      cells within the PFC. In this study, three groups of rat pups were used:
      intubated with alcohol (5.25 g/kg/day; AE), sham intubated (SI), or suckle
      controls (SC) on PD 4-9. On PD 26-30 rats were anesthetized, perfused with saline
      and brains were processed for Golgi-Cox staining. Basilar dendritic complexity,
      spine density, and spine phenotypes were evaluated for Layer II/III neurons in
      the medial PFC. Results indicate that AE rats have an altered basilar dendritic
      complexity due to a significant decrease in both length and number of
      intersections in proximity to the neuronal soma. Furthermore, spine density
      patterns of basilar dendrites remain unchanged while the density of mature vs.
      immature spines significantly changes. These effects were not seen in the apical
      dendrites, indicating alcohol's influence on different neuronal parts in a single
      cell. In addition, these results suggest that the innervations of the soma and
      basilar dendrites by thalamic projections may play a role. Thus, our data
      demonstrates that postnatal exposure to alcohol produces changes in the neuronal
      organization of rat adolescent PFC that may affect the performance on prefrontal
      dependant behavioral tasks.

PMID- 19771590
TI  - Nicotine withdrawal produces a decrease in extracellular levels of dopamine in
      the nucleus accumbens that is lower in adolescent versus adult male rats.
AB  - The behavioral effects of nicotine withdrawal are lower in adolescent versus
      adult rats. However, the neurochemical mechanisms that mediate these
      developmental differences are unknown. Previous studies have shown that
      extracellular levels of dopamine in the nucleus accumbens (NAcc) are reduced in
      adult rats experiencing withdrawal. This study compared dopamine levels in the
      NAcc of male adolescent and adult rats experiencing nicotine withdrawal. Animals
      were prepared with subcutaneous pumps that delivered an equivalent nicotine dose
      in these age groups. Following 13 days of nicotine exposure, rats were implanted
      unilaterally with microdialysis probes into the NAcc and ipsilateral ventral
      tegmental area (VTA). The next day, dialysate levels were collected following
      systemic administration of the nicotinic-receptor antagonist mecamylamine to
      precipitate withdrawal. Mecamylamine produced an average % decrease in NAcc
      dopamine that was lower in adolescents (20%) versus adults (44%). Similar
      developmental differences were observed with the dopaminergic (DOPAC and HVA) but
      not serotonergic (5-HIAA) metabolites. A follow-up study compared NAcc dopamine
      in adolescent and adult rats receiving intra-VTA administration of bicuculline,
      which reduces gamma-aminobutyric acid (GABA) inhibition of dopamine transmission.
      The results revealed that blockade of GABA(A) receptors in the VTA produced a two
      fold increase in NAcc dopamine of adults but not adolescents. These results
      provide a potential mechanism involving dopamine that mediates developmental
      differences in nicotine withdrawal. Specifically, they suggest that GABA systems
      are underdeveloped during adolescence and this reduced inhibition of dopamine
      neurons in the VTA may lead to reduced decreases in NAcc dopamine of young
      animals experiencing withdrawal.

PMID- 19771591
TI  - SSRI antidepressants do not confound single photon emission computed tomography
      (SPECT) imaging studies using the alpha4beta2 nicotinic acetylcholine receptor
      [123I]5-I-A85380 ligand: in vivo and in vitro evidence.
AB  - PURPOSE: In clinical molecular imaging the interaction between antidepressant
      medication and SPECT ligands is a significant potential confound. This study
      measured nAChR availability, as determined by SPECT imaging, on and off selective
      serotonin reuptake inhibitors in first episode depressed patients. METHODS: Five
      patients in their first episode of major depressive disorder (MDD) on a single
      SSRI underwent [(123)I]5-I-A85380- SPECT neuroimaging prior to stopping their
      medication and again 6 weeks following medication cessation. Autoradiography of
      post mortem brain tissue with [(125)I]5-I-A85380 in the presence or absence of
      four commonly prescribed antidepressants was also assessed. RESULTS: SSRI
      antidepressants did not affect the relative binding availability of alpha4beta2
      nicotinic acetylcholine receptors for the [(123)I]5-I-A85380 ligand in vivo.
      Radioligand binding in vitro was unaffected by a single, high pharmacological
      concentration of antidepressants. CONCLUSION: SPECT imaging studies using
      [(123)I]5-I-A85380 to measure alpha4beta2 nAChR availability in depressed
      patients are unlikely to be confounded to a major degree by concurrent
      antidepressant medication.

PMID- 19771592
TI  - The selective alpha1 adrenoceptor antagonist HEAT reduces L-DOPA-induced
      dyskinesia in a rat model of Parkinson's disease.
AB  - In Parkinson's disease (PD), the long term use of L-DOPA results in major adverse
      effects including dyskinesia or abnormal involuntary movements. The present study
      focuses on the effect of the selective alpha(1) adrenoceptor antagonist HEAT (2
      [[beta-(-4-hydroxyphenyl)ethyl]aminomethyl]-1-tetralone) in the 6-hydroxydopamine
      rat model of L-DOPA-induced dyskinesia. We demonstrate that the selective
      alpha(1) adrenoceptor antagonist HEAT (1 and 2 mg kg(-1)), the alpha(2)
      adrenoceptor antagonist idazoxan (9 mg kg(-1)), and the nonselective
      beta(1)/beta(2) adrenoceptor antagonist propranolol (20 mg kg(-1)) alleviate
      dyskinetic movements induced by L-DOPA. Furthermore, the adrenoceptor antagonists
      at the doses used did not influence exploratory behavior in the open field system
      indicating that the antidyskinetic effect is not due to a reduction in general
      motor activity. Intrastriatal administration of the selective alpha(1)
      adrenoceptor agonist cirazoline via reverse in vivo microdialysis did not induce
      dyskinesia. Additionally, we measured plasma, brain, and CSF levels of HEAT. HEAT
      is a CNS active compound with a brain/plasma and CSF/plasma ratio of 4.29 and
      0.15, respectively, which is appropriate for the investigation of alpha(1)
      mediated mechanisms in CNS disorders. In conclusion, these results demonstrated
      for the first time that a alpha(1) adrenoceptor antagonist reduced L-DOPA-induced
      dyskinesia in a rat model. Further studies assessing the risk benefit in
      comparison to existing therapies are needed before considering alpha(1)
      adrenoceptor antagonists as a target for the development of new antidyskinetic
      compounds.

PMID- 19771595
TI  - Prioritizing research: Patients, carers, and clinicians working together to
      identify and prioritize important clinical uncertainties in urinary incontinence.
AB  - AIMS: Research often neglects important gaps in existing evidence. Throughout
      healthcare, clinicians and patients face avoidable "clinical uncertainties"
      daily, making decisions about treatments without reliable evidence about their
      effects. This partnership of patients and clinicians aimed to identify and
      prioritize "clinical uncertainties" relating to treatment of urinary incontinence
      (UI). METHODS: UK clinician and patient organizations whose remit includes UI
      were invited to participate. Participating organizations consulted memberships to
      identify "uncertainties" affecting treatment decisions. "Uncertainties" were also
      identified in published research recommendations. Prioritization involved two
      phases: shortlisting of "uncertainties" by organizations; patient-clinician
      prioritization using established consensus methods. Prioritized "uncertainties"
      were verified by checking any available relevant up-to-date published systematic
      reviews. RESULTS: Thirty organizations were invited; 8 patient and 13 clinician
      organizations participated. Consultation generated 417 perceived "uncertainties,"
      research recommendations 131. Refining, excluding and combining produced a list
      of 226. Prioritization shortlisted 29 "uncertainties," then a "top ten" (5
      submitted by clinicians, 4 by patients, 1 from research recommendations).
      CONCLUSIONS: The partnership successfully developed and tested a systematic and
      transparent methodology for patient-clinician consultation and consensus. Through
      consensus, unanswered research questions of importance to patients and clinicians
      were identified and prioritized. The final list reflects the heterogeneity of
      populations, treatments and evidence needs associated with UI. Some prioritized
      "uncertainties" relate to treatments that are widely used yet whose effects are
      not thoroughly understood, some to access to care, some to precise surgical
      questions. Research needs to address the uncertainties range from systematic
      reviewing to primary research.

PMID- 19771593
TI  - Effect of the environment on the dendritic morphology of the rat auditory cortex.
AB  - The present study aimed to identify morphological correlates of environment
      induced changes at excitatory synapses of the primary auditory cortex (A1). We
      used the Golgi-Cox stain technique to compare pyramidal cells dendritic
      properties of Sprague-Dawley rats exposed to different environmental
      manipulations. Sholl analysis, dendritic length measures, and spine density
      counts were used to monitor the effects of sensory deafness and an auditory
      version of environmental enrichment (EE). We found that deafness decreased apical
      dendritic length leaving basal dendritic length unchanged, whereas EE selectively
      increased basal dendritic length without changing apical dendritic length. On the
      contrary, deafness decreased while EE increased spine density in both basal and
      apical dendrites of A1 Layer 2/3 (LII/III) neurons. To determine whether stress
      contributed to the observed morphological changes in A1, we studied neural
      morphology in a restraint-induced model that lacked behaviorally relevant
      acoustic cues. We found that stress selectively decreased apical dendritic length
      in the auditory but not in the visual primary cortex. Similar to the acoustic
      manipulation, stress-induced changes in dendritic length possessed a layer
      specific pattern displaying LII/III neurons from stressed animals with normal
      apical dendrites but shorter basal dendrites, while infragranular neurons (Layers
      V and VI) displayed shorter apical dendrites but normal basal dendrites. The same
      treatment did not induce similar changes in the visual cortex, demonstrating that
      the auditory cortex is an exquisitely sensitive target of neocortical plasticity,
      and that prolonged exposure to different acoustic as well as emotional
      environmental manipulation may produce specific changes in dendritic shape and
      spine density.

PMID- 19771596
TI  - Executive summary: The International Consultation on Incontinence 2008--Committee
      on: "Dynamic Testing"; for urinary or fecal incontinence. Part 2: Urodynamic
      testing in male patients with symptoms of urinary incontinence, in patients with
      relevant neurological abnormalities, and in children and in frail elderly with
      symptoms of urinary incontinence.
AB  - AIMS: The members of 'The International Consultation on Incontinence 2008 (Paris)
      Committee on Dynamic Testing' provide an executive summary of the chapter
      'Dynamic Testing' that discusses (urodynamic) testing methods for patients with
      signs and or symptoms of urinary incontinence. Testing of patients with signs and
      or symptoms of fecal incontinence is also discussed. METHODS: Evidence based and
      consensus committee report. RESULTS: The chapter 'Dynamic Testing' is a
      continuation of previous Consultation reports added with a new systematic
      literature search and expert discussion. Conclusions, based on the published
      evidence and recommendations, based on the integration of evidence with expert
      experience and discussion are provided separately, for transparency. CONCLUSION:
      This second part of a series of three articles summarizes the committee's
      recommendations about: 'Urodynamic testing of male patients with symptoms of
      incontinence, of patients with relevant neurological abnormalities, testing of
      children and of frail elderly with symptoms of incontinence' and includes only
      the most recent and relevant literature references.

PMID- 19771594
TI  - Neuromuscular diseases associated with HIV-1 infection.
AB  - Neuromuscular disorders are common in human immunodeficiency virus (HIV); they
      occur at all stages of disease and affect all parts of the peripheral nervous
      system. These disorders have diverse etiologies including HIV itself, immune
      suppression and dysregulation, comorbid illnesses and infections, and side
      effects of medications. In this article, we review the following HIV-associated
      conditions: distal symmetric polyneuropathy; inflammatory demyelinating
      polyneuropathy; mononeuropathy; mononeuropathy multiplex; autonomic neuropathy;
      progressive polyradiculopathy due to cytomegalovirus; herpes zoster; myopathy;
      and other, rarer disorders.

PMID- 19771597
TI  - Histological validation of ultrasound-guided neurography in early nerve
      regeneration.
AB  - Ultrasound-guided near-nerve neurography is a new tool that can be used to assess
      nerve regeneration before reinnervation occurs. In this study, ultrasound-guided
      near-nerve measurements were validated against axon diameter counts in rabbits
      during a 15-week regeneration period after a crush lesion of their peroneal
      nerve. The course of the nerve was determined ultrasonically, and the active near
      nerve needle electrode was maneuvered just next to the nerve under ultrasound
      guidance. Measured action potentials were compared with axon diameter counts from
      histological sections of these same nerves. A moderate to good positive
      correlation was found, which reached a maximum of 0.7 at a cut-off of 3 microm,
      corresponding to the minimal size of the myelinated axons. Our results suggest
      that, following a similar validation study in humans, ultrasound-guided near
      nerve neurography may be clinically useful when early evaluation of nerve
      activity is needed.

PMID- 19771598
TI  - Tolterodine causes measurable restoration of urethral sensation in women with
      urge urinary incontinence.
AB  - INTRODUCTION & HYPOTHESIS: Determine if treatment of urge incontinence with
      tolterodine results in changes in bladder and/or urethral sensation using Current
      Perception Threshold (CPT) testing. METHODS: Women with >or=1 incontinence
      episode on 7-day diary were treated with 4 mg of long-acting tolterodine for 2
      months. At baseline and 2-months, participants had CPT testing of the urethral
      and bladder at 3 frequencies 2000, 250, and 5 Hz. Baseline and post-treatment
      measures were compared using Wilcoxon Signed Rank Test. RESULTS: Seventeen women
      underwent baseline CPT testing. Four discontinued medication due to side effects
      and did not have repeated testing. Urethral CPT at 250 Hz was lower after
      treatment (median 1.3 [Interquartile range .69-2.1] and .75 [.45-1.2], p = .003)
      and at 5 Hz trended toward a significant decrease (1.1 [1-1.9] and .84 [.32-1.1],
      p = .06). CONCLUSIONS: Urethral sensitivity improves after 2-months of
      tolterodine, suggesting it may restore urethral sensory nerves in addition to
      known motor effects.

PMID- 19771603
TI  - [Proceedings of the 134th Internal Medicine Seminar--XXIII. Vanysek Seminar.
      Brno, 27, March 2009].

PMID- 19771604
TI  - Proceedings and abstracts of the 7th Annual Safety Pharmacology Society Meeting.
      Edinburgh, Scotland. September 19-21, 2007.

PMID- 19771605
TI  - Fomepizole for toxic alcohol poisoning.

PMID- 19771606
TI  - More on B-cell-depleting induction therapy and acute cellular rejection.

PMID- 19771609
TI  - Clinical update retraction.

PMID- 19771607
TI  - Medicaid's medical transportation assurance: origins, evolution, current trends,
      and implications for health reform.
AB  - This policy brief examines Medicaid's assurance of medical transportation in the
      context of medically necessary but non-emergency health care. Reviewing the
      origins and evolution of the assurance and presenting the results of a 2009
      survey of state Medicaid programs, the results of this analysis underscore
      Medicaid's unique capacity to not only finance medically necessary health care
      but also the services and supports that enable access to health care by low
      income persons since Medicaid covers non-emergency medical transportation. This
      ability to both finance health care and enable its use moves to the forefront as
      Congress considers whether to assist low income persons in health reform through
      Medicaid expansions or via subsidies for traditional health insurance, which
      typically does not provide comparable transportation coverage.

PMID- 19771610
TI  - RIKEN scientist arrested.

PMID- 19771611
TI  - A/H1N1 influenza virus passes to birds.

PMID- 19771612
TI  - Vaccines Against Meningococcus - An update of the progresses in meningitis
      prevention. Proceeding of the Meningococcus Scientific Exchange Meeting. Siena,
      Italy. July 1-3, 2008.

PMID- 19771613
TI  - Proceedings of the 3rd German-Japanese Symposium of Pediatric Neurology. Munich,
      Germany. September 8-10, 2008.

PMID- 19771614
TI  - Special issue dedicated to the memory of Petra Sperling. Proceedings of the 18th
      International Symposium on Plant Lipids. July 20-25, 2008. Bordeaux, France.

PMID- 19771615
TI  - Environmental records of anthropogenic impacts on coastal ecosystems. Proceedings
      of a special session of Ocean Sciences 2008. March 2-7, 2008. Orlando, Florida,
      USA.

PMID- 19771616
TI  - Promises and threats.
AB  - Last week, six major healthcare industry players got together and sent a letter
      to President Barack Obama on health reform. The initiatives outlined could curb
      healthcare spending by $1 trillion to $1.7 trillion during the next decade.
      Regarding the projections, Raymond Gibbons, left, from the Mayo Clinic, says, "I
      would express concern as to whether they are bold enough and provide enough
      detail."

PMID- 19771617
TI  - Small change, big savings?

PMID- 19771618
TI  - One has state-federal issues ... Mann to deal with entitlement vs. flexibility:
      Smith.

PMID- 19771619
TI  - . . . for another it's transparency. Hamburg creates task force, GAO issues
      reports.

PMID- 19771620
TI  - Left out of the discussion. Single-payer advocates still trying to be heard.

PMID- 19771621
TI  - Land of the lost. GAO scolds IHS on $3.5 million in missing property.

PMID- 19771622
TI  - More exclusive Community. Six of eight Triad joint ventures have come undone.

PMID- 19771624
TI  - A storm in Southern California. Tri-City Medical beset by infighting, money woes.

PMID- 19771623
TI  - Healthcare stalling in Motor City. GM's problems has healthcare revenue
      downshifting.

PMID- 19771625
TI  - Doing the right thing. Healthcare industry can reform itself with the right
      motivation.

PMID- 19771626
TI  - Short-term 'bug' rampant. Maintaining infection-control spending imperative,
      despite recession.

PMID- 19771627
TI  - Into the red. Annual survey of hospital systems shows not-for-profits posted an
      overall net loss in 2008; for-profit chains bucked the trend.

PMID- 19771628
TI  - [Effect of ichphans on the structural properties of erythrocyte membranes].
AB  - Morphological transformation of erythrocytes and structural changes in the
      erythrocyte membrane have been revealed by scanning electron microscopy and spin
      probe technique. These effects were caused by the incorporation of ichphans, new
      generation drugs combining antioxidant and anticholinesterase effects, into the
      erythrocyte membrane and their distribution in the intramembrane space. Different
      distribution and modulatory effect of the derivatives with different hydrophobic
      properties have been shown. The derivatives with 8 and 10 carbon atoms in the
      aliphatic substituent were the most efficient modifiers of the membrane structure
      and morphology of erythrocytes.

PMID- 19771629
TI  - [Effect of photoperiod on growth, physiological and hematological indices of
      juvenile Siberian sturgeon Acipenser baerii].
AB  - The effect of photoperiod on the growth of juvenile Siberian sturgeon Acipenser
      baerii has been studied in aquarium experiments. The maximum growth rate of
      juvenile Siberian sturgeon was observed under 12, 16, and 24 h photoperiods. This
      was accompanied by high respiratory rate and total food consumption and
      conversion. Rearing in the dark significantly decreased these indices. The
      hematological indices were within the normal range under optimal photoperiodic
      conditions. Pronounced neutrophilia and leukopenia were observed in the absence
      of light.

PMID- 19771630
TI  - [The effect of short-term daily temperature drops on the processes of
      organogenesis in Cucumis sativus L. under conditions of different photoperiods].
AB  - The effect of nightly temperature drops of different durations (2, 4, and 6 h) on
      the processes of apical and axillary meristem organogenesis was studied in young
      Cucumis sativus L. under short photoperiod (day/night, 10/14 h), long photoperiod
      (16/8 h), and continuous light. Nightly temperature drops for 2 h had no effect
      on cucumber development under all studied photoperiods; however, longer
      temperature drops (4-8 h) accelerated the development under long photoperiod and
      continuous light. Short-term exposures to low temperature under continuous light
      considerably increased lateral branching of cucumber plants.

PMID- 19771631
TI  - For the patient. The widening gap of diabetes between American Indian/Alaska
      Native young adults and non-Hispanic White young adults.

PMID- 19771632
TI  - For the patient. Little education and low income are more associated with
      diabetes than ethnicity.

PMID- 19771633
TI  - For the patient. Mexican Americans less likely to be screened for cancer compared
      to Whites.

PMID- 19771634
TI  - Shake, don't rattle, roles. With financial pressures afoot, health systems look
      to change management structure.
AB  - As pressure builds on hospitals, some are taking an extreme approach to
      reorganization by totally revamping their management. At the University of
      Chicago Medical Center, David Hefner, left, was part of such a overhaul, which
      included eliminating his job as president. "I just think we could go to any of
      these healthcare enterprises and do some of the kind of recombining of functions
      and reduce executive management."

PMID- 19771635
TI  - A 'Lion'-sized loss. Kennedy's death could have impact on reform.

PMID- 19771636
TI  - FAH: Ignore quality targets. Letter to CMS, ONC addresses funds for EHRs.

PMID- 19771637
TI  - States press on. Wash. holdup doesn't stop some from health agenda.

PMID- 19771638
TI  - What's in our wallet? Providers concerned D.C. might hit them up for cash.

PMID- 19771639
TI  - First line of defense. Worries flare about H1N1 vaccinations for workers.

PMID- 19771640
TI  - Borrowing boon. More explore Federal Home Loan Banks backing.

PMID- 19771641
TI  - CQC names high death-rate trusts. Patient safety. List sparks fears that
      organisations will be seen as 'bad apples'.

PMID- 19771642
TI  - Swine flu. Immunisation choices risk creating local variations. PCTs decide on
      vaccine priority.

PMID- 19771643
TI  - Management stars need a leg-up to rise to the top.

PMID- 19771644
TI  - On cash in a cold climate.

PMID- 19771645
TI  - On patient experience. The standards glass is half empty.

PMID- 19771646
TI  - Retirement. A career's worth of wisdom on tap.

PMID- 19771647
TI  - Access. Listen closely to what deaf patients want.

PMID- 19771648
TI  - Afghanistan. Extreme operations.

PMID- 19771649
TI  - Smoking. Sticking with quitting.

PMID- 19771650
TI  - From tragedy to advocacy.
AB  - Some of the fiercest proponents of the patient-safety movement are motivated by
      personal tragedies-the loss of a child or husband to medical errors. These
      advocates are determined to speak up for what's right for patients.."A lot of
      healthcare is designed around those of us providing the care. How can you
      possibly understand what patients want if they're not in the room?" says Mark
      Novotny, left.

PMID- 19771652
TI  - Uncompensated unrest. AHA, HFMA oppose CMS' plan on reporting.

PMID- 19771651
TI  - A POTUS proposal. Obama to state his case to Congress, Americans.

PMID- 19771653
TI  - Forging a new system. CHI, Trinity agree to merge hospitals in Idaho, Ore.

PMID- 19771654
TI  - Suppliers shuffle, deal. Spate of restructuring, exec changes, acquisitions.

PMID- 19771655
TI  - Legacy of practicality, compromise. Kennedy's healthcare work was about passing
      bills, not furthering ideology.

PMID- 19771656
TI  - Award of excellence/built. Grand Itasca Clinic & Hospital, Grand Rapids, Minn.

PMID- 19771657
TI  - Honorable mention/built. Children's Medical Center at Legacy, Plano, Texas.

PMID- 19771658
TI  - Honorable mention/built. Kennedy Krieger Institute, Harry and Jeanette Weinberg
      Building, Outpatient Center, Baltimore.

PMID- 19771659
TI  - Honorable mention/built. Stanford Medicine Outpatient Center, Redwood City,
      Calif.

PMID- 19771660
TI  - Findings of research misconduct.

PMID- 19771661
TI  - Biological measures of the standard of living.
AB  - When economists investigate long-term trends and socioeconomic differences in the
      standard of living or quality of life, they have traditionally focused on
      monetary measures such as gross domestic product--which has occupied center stage
      for over 50 years. In recent decades, however, scholars have increasingly
      recognized the limitations of monetary measures while seeking useful
      alternatives. This essay examines the unique and valuable contributions of four
      biological measures--life expectancy, morbidity, stature, and certain features of
      skeletal remains--to understand levels and changes in human well-being. People
      desire far more than material goods and in fact they are quite willing to trade
      or give up material things in return for better physical or psychological health.
      For most people, health is so important to their quality of life that it is
      useful to refer to the "biological standard of living." Biological measures may
      be especially valuable for historical studies and for other research
      circumstances where monetary measures are thin or lacking. A concluding section
      ruminates on the future evolution of biological approaches in measuring
      happiness.

PMID- 19771662
TI  - [Survival after rectal cancer has improved considerably in Denmark--secondary
      publication].
AB  - Danish rectal cancer patients previously had an inferior prognosis compared with
      the other Scandinavian countries. An analysis of overall and relative survival in
      1994-2006 was based on the Danish Colorectal Cancer Group's national colorectal
      cancer databases and the Central Population Registry. The 5-year overall survival
      in 10,632 operated patients increased from 37% to 51% and the 5-year relative
      survival rose from 46% to 62%. In conclusion, the prognosis improved considerably
      mainly due to implementation of total mesorectal excision, improved preoperative
      staging and centralised surgical treatment.

PMID- 19771663
TI  - [Nurse administered propofol sedation in connection with endoscopy].

PMID- 19771666
TI  - [Psychologists' participation in psychiatric rounds].

PMID- 19771665
TI  - Autism spectrum disorders: navigating in uncharted waters.

PMID- 19771667
TI  - [We have sensible euthanasia legislation].

PMID- 19771668
TI  - [Psychologists' participation in psychiatric rounds].

PMID- 19771669
TI  - [Never sick during the weekend].

PMID- 19771670
TI  - Melanie Klein and Repression: an examination of some unpublished Notes of 1934.
AB  - Fifteen pages of unpublished Notes were found in the Melanie Klein Archives
      dating from early 1934, a crucial moment in Klein's development. She was at this
      time, 1934, moving away from child analysis, whilst also rethinking and revising
      her allegiance to Karl Abraham's theory of the phases of libidinal development.
      These Notes, entitled "Early Repression Mechanism," show Klein struggling to
      develop what became her characteristic theories of the depressive position and
      the paranoid-schizoid position. Although these Notes are precursors of the paper
      Klein gave later to the IPA Congress in 1934, they also show the origins of the
      emphasis she and her followers eventually gave to "splitting" rather than
      repression. The Notes give us an insight into the way that she worked clinically
      at the time. We see Klein's confidence develop as she diverged from the classical
      theories and technique. Her ideas were based on close attention to the detail of
      her clinical material, rather than attacking theoretical problems directly. The
      Notes show her method of struggling to her own conclusions, and they offer us a
      chance to grasp the roots of the subsequent controversy over Kleinian thought.

PMID- 19771672
TI  - Micro and nano technologies in Bioanalysis. Preface.

PMID- 19771671
TI  - [Introduction to methods of economic modelling: a primer for orthopaedic surgeons
      and traumatologists].
AB  - AIM: Health economics and cost-efficiency are ubiquitously present issues in
      present day orthopaedic surgery. These subjects, however, are almost exclusively
      dealt with by economists and policy makers, while medical professionals rarely
      take part, quite often because of insufficient methodological knowledge. This
      report presents the basics of economic evaluation to orthopaedic surgeons to
      facilitate informed discussion. METHOD: This text reviews the basic methodology
      of economic evaluation and pertinent findings for orthopaedic surgery. RESULTS:
      Economic evaluation combines costs and consequences of medical treatments.
      Partial analyses study costs only, while complete studies include different
      parameters of consequence. Cost-effectiveness analysis sets cost and
      effectiveness in natural metrics in relation, while cost-utility analyses present
      consequences as quality-adjusted life years. Cost-benefit analyses translate both
      costs and consequences into money value and thus produce a net benefit.
      Orthopaedic research focuses mainly on cost-utility analyses, yet their number
      and quality, despite both have been rising over the last years, are mostly
      insufficient to come to unequivocal conclusions or to produce clear
      recommendations. CONCLUSION: The trend for an increasing demand for economic
      evaluations in orthopaedic surgery will continue unabated. Both patients and
      medical professionals would benefit if orthopaedic surgeons received instruction
      in economic evaluations in order to be able to take part in such studies or to
      meaningfully discuss such matters.

PMID- 19771673
TI  - [Latissimus dorsi transfer--comparison of results after primary and revision
      surgery: a retrospective matched-pair analysis].
AB  - AIM: Latissimus dorsi transfer (LdT) has been proposed for the treatment of
      irreparable rotator cuff tears of the infra- and supraspinatus. The purpose of
      this retrospective study was to evaluate the results of latissimus dorsi transfer
      in revision surgery in comparison to primary surgery. METHOD: Between 1998 and
      2005 a group of 124 patients has been treated with a latissimus dorsi transfer.
      From this group 34 patients (Group 1 = revision LdT n = 17, Group 2 = primary LdT
      n = 17)were examined in a retrospective matched-pair study after an average
      follow-up of 20 months (Group 1) and 28 months (Group 2) by clinical examination
      and X-ray. Functional results were assessed with use of the age- and gender
      matched Constant Score (CS). RESULTS: The age- and gender-matched Constant Score
      increased significantly in both groups from preoperatively 51% in Group 1 and 57%
      in Group 2 up to a postoperative score of 73% in Group 1 and 84% in Group 2 (p =
      0.001/p = 0.007). By comparison of the 2 groups there is a significantly higher
      postoperative age- and gender-matched Constant Score for Group 2 (p = 0.03).
      Active ROM showed postoperatively no significant difference (Abd/Flex p = 0.8).
      The Hornblower sign is significantly more frequently positive in Group 1(p <
      0.001). The comparison of arthroscopically and open previous surgery for the
      subgroups of revision latissimus dorsi transfer shows a trend for an increased
      postoperative age- and gender-matched Constant Score in the arthroscopic group
      (82%/69% p = 0.06) with a preoperative CS of 50%/52% (p = 0.9). There is no
      significant difference in the incidence of postoperative complications.
      CONCLUSION: Considering the correct indication for latissimus dorsi transfer
      there is no difference for reduction of pain and active ROM between primary and
      revision surgery. But the revision cases show a significantly lower age- and
      gender-matched Constant Score and a higher incidence of a positive Hornblower
      sign. A higher risk of postoperative complications for the revision group could
      not be found. In summary, the latissimus dorsi transfer was of significant
      benefit for both groups and we can also recommend this technique for revision
      surgery.

PMID- 19771674
TI  - [Influence of sex and side dominance on the results of quantitative, three
      dimensional motion analysis of the upper extremities].
AB  - AIM: Clinical assessment does not provide objective and quantitative evaluation
      of the shoulder function. Based on instrumental gait analysis a system for three
      dimensional motion analysis of the upper extremities has been developed. The aim
      of this study is to evaluate the results of instrumental upper extremity motion
      analysis with respect to dependence on sex and side dominance. METHOD: 16 healthy
      subjects (8 male, 8 female, mean age 26 years) were included. Three-dimensional
      motion analysis was carried out with a video-based system and passive markers.
      All subjects performed two movement tasks representing activities of daily living
      (task A: reaching the neck, task B: removing a parking token). All joint angles
      of the upper extremity were recorded and graphically displayed. Additionally, a
      calculation of quantitative parameters was performed. RESULTS: Contrary to
      expectations the task "reaching the neck" was not combined with external shoulder
      rotation. Females performed most of the tasks quicker and with higher
      reproduction accuracy. Movement reproduction accuracy was rarely dependent on
      dominance. CONCLUSION: Three-dimensional upper extremity motion analysis of
      activities of daily living allows a precise and quantitative evaluation of
      movement patterns. The differences with respect to sex and side in a healthy
      group have to be respected in studies dealing with comparative shoulder function.

PMID- 19771675
TI  - [Traumatic thoracic spine fractures: inter- and intraobserver reliability of
      vertebral, local and segmental kyphosis in lateral X-rays].
AB  - BACKGROUND: The evaluation of the vertebral, local and segmental kyphosis
      according to Cobb is usual practice in the determination of traumatic, idiopathic
      and degenerative spinal deformities. The present study compares the inter- and
      intraobserver reliability of these 3 angles in the lateral X-rays of thoracic
      spine fractures with spinal kyphosis. METHODS: From 1999 till 2007 all patients
      with adequate X-rays, age < 50 years, traumatic, thoracic spine fracture,
      kyphotic deformity and surgical intervention were included. The vertebral, local
      and segmental kyphosis were assessed by 3 observers at 2 time-points in the
      preoperative lateral X-rays. RESULTS: 63 patients, 11 women and 52 men, with a
      mean age of 34 years could be evaluated. In all cases an adequate trauma had led
      to the fracture. The most common trauma was an injury with a motorcycle; the 12th
      thoracic vertebra was most commonly affected. The segmental kyphosis showed
      'excellent' results for inter- and intraobserver reliability (O-ICC: 0.8189 and O
      ICC:0.8003). 'Good' results for inter- and intraobserver reliability could be
      evaluated for the vertebral (O-ICC: 0.7797 and O-ICC: 0.7797) and local (O-ICC:
      0.7532 and O-ICC: 0.7296) kyphosis. CONCLUSION: Due to excellent and good results
      for inter- and intraobserver reliability of the segmental,vertebral and local
      kyphosis in the lateral X-rays of the thoracic spine, these angles could be a
      helpful tool, indicating a surgical procedure in traumatic thoracic fractures
      with kyphosis. Further possible interesting applications in the usage of these 3
      angles could be the observation of the vertebral sintering in surgically or
      conservatively treated vertebral fractures. Appropriate studies should be
      performed before general recommendations can be given.

PMID- 19771676
TI  - SOGC Joint Policy Statement on Normal Childbirth.

PMID- 19771677
TI  - [Operative therapy for intraspinal empyema: a retrospective study of 23
      patients].
AB  - OBJECTIVE: Intraspinal empyema is a rare entity in spinal surgery. This study
      analyses the results after operating in 23 patients. MATERIAL AND METHODS: This
      is a retrospective study of 23 patients suffering from intraspinal empyema
      treated operatively in our department. The data were obtained by analysing the
      patient documents including the radiological and microbiological data. RESULTS:
      18 patients suffered from different neurological deficits ranging from isolated
      mild hypaesthesia to paraplegia (n = 3). The operation was done as a one-level (n
      = 13), two-level (n = 8)or three-level (n = 2) microsurgical fenestration
      followed by irrigation and drainage of the pus. Staphylococcus aureus was the
      most frequent triggering organism. After a follow-up of 7 months 1 patient had
      died because of septic complications. Neurological deficits improved in 14
      patients but 3 patients were still disabled in their daily life. CONCLUSION:
      Epidural spinal empyema remains a challenge in spine surgery. Persistent
      neurological deficits and lethal complications make it a severe problem.
      Management comprises urgent surgical evacuation of the pus followed by targeted
      antibiotic therapy.

PMID- 19771678
TI  - Is patient litigation part of the regulatory framework for surgical devices?

PMID- 19771679
TI  - George Wilbur: Otto Rank and Hanns Sachs.
AB  - George Wilbur, a pioneering Cape Cod psychoanalytic psychiatrist, was a long
      standing editor of the journal "American Imago," and an excellent source of
      information about the Viennese analysts Otto Rank and Hanns Sachs. Wilbur was
      also knowledgeable about the early reception of psychoanalysis in the Boston
      community.

PMID- 19771680
TI  - The Correspondence of Bruno Bettelheim and Rudolf Ekstein.
AB  - This paper provides the historical, cultural, and clinical context for the
      relationship between Bruno Bettelheim (1903-1990) and Rudolf Ekstein (1912-2005).
      Both were Viennese-born and trained intellectuals who received doctorates in the
      human sciences from the University of Vienna in 1937. Both were deeply identified
      with lay analysis, emphasizing that for psychoanalysis to perpetuate itself it
      needed to promote serious and rigorous forms of research. Because Bettelheim was
      the better known of the two, this introduction focuses on Ekstein's family
      history, with special emphasis on his experience of loss and trauma and his
      capacity to recover from personal and educational obstacles. It argues that
      Ekstein was a representative product of Austro-Marxism in the period between the
      wars, embracing the ethical brand of democratic socialism and group solidarity
      that was integral to the theory and practice of Austrian Social Democracy. It
      discusses Ekstein's training with Moritz Schlick in philosophy and his immersion
      in the Vienna Circle of logical positivism. From Schlick, Ekstein evolved into a
      philosophical thinker who learned how to think his own thoughts. Ekstein joined
      the circle of psychoanalytic pedagogues who clustered around the Vienna
      Psychoanalytic Society, under the tutelage of Willi Hoffer, August Aichhorn and,
      above all, Anna Freud. The clinical component of psychoanalysis emanated from his
      commitment to understanding the inner world of the child. Bettelheim and Ekstein
      first became aware of each other from reading the analytic literature and finally
      met in America in the 1950s. They shared a professional interest in conducting
      research and doing clinical work on severely disturbed children and adolescents,
      including those with psychotic, borderline and autistic diagnoses. They debated
      the value of milieu therapy versus psychoanalytically oriented psychotherapy on
      such children. As their relationship evolved, the two collaborated and began a
      fascinating correspondence that gradually evolved into an intimate friendship.
      They both engaged in a polemic with Bernard Rimland, who was massively critical
      of their clinical work and a hostile critic of psychoanalytic approaches to the
      treatment of disturbed children. Rimland was an advocate of a neurological
      approach to mental illness, with an emphasis on biology and psychopharmacology.
      The 22 letters that constitute the Bettelheim-Ekstein exchange began with
      clinical concerns, including the varieties of solitude, isolation and
      countertransference disruptions that may trouble the psychoanalytic researcher
      and clinician in dealing with primitively disordered children. It moves to other
      issues, including mutual support during the Rimland Affair. As the two became
      more friendly, a pattern of good-natured competition and envy appeared. The two
      engaged in a heated exchange on the question of whether contemporary Vienna
      remained as anti-Semitic as it had been in their respective youths: Bettelheim,
      the concentration camp survivor, argued that nothing had changed and that most
      Austrians remained viscerally anti-Semitic; Ekstein, the Austro-Marxist,
      contended that one could not blame a generation born after World War II, holding
      that in his experience many Austrians had examined their consciences and held
      distinctly different options from their parents or grandparents. Toward the end
      of their correspondence, we encounter Ekstein's tender sensitivity to
      Bettelheim's descent into depression as a result of the death of his wife, Trude,
      leading eventually to recurrent episodes of suicidal ideation and plans for his
      own suicide. The letters testify to a unique friendship with a somewhat old-world
      quality.

PMID- 19771681
TI  - Global use of rotavirus vaccines recommended.

PMID- 19771682
TI  - Greater equity in health should be a progress indicator.

PMID- 19771683
TI  - Pedestrians, cyclists among main road traffic crash victims.

PMID- 19771684
TI  - Call to protect hospitals, schools from impact of disasters.

PMID- 19771685
TI  - Rescuing psychoanalysis from Freud: the common project of Stekel, Jung and
      Ferenczi.
AB  - This article offers an extended discussion of Wilhelm Stekel's "On the History of
      the Analytic Movement" (1926), published in English translation for the first
      time in "Psychoanalysis and History" 7(1) in 2005. It begins with a critique of
      the presentation of Stekel's text by Jaap Bos, who takes a purely rhetorical
      approach that seeks to exclude a psychological analysis of the author's motives.
      Bos's characterization of Stekel is likewise contested as unduly negative in
      crucial respects. The second section argues that it remains the task of the
      historian to search for truth. Attacks on the credibility of Jung by Harold Blum
      and Kurt Eissler are shown to reflect a bias that causes them to neglect the
      empirical evidence corroborating Jung's testimony concerning key events in his
      relationship to Freud. The third section lays out the numerous ways in which
      Stekel, Jung and Ferenczi independently arrived at remarkably similar judgements
      concerning Freud's character, and how his human failings exerted a harmful effect
      on the development of psychoanalysis. The final section moves to a discussion of
      how Stekel joins with Jung and Ferenczi in defining a common project of rescuing
      what is best in psychoanalysis from Freud's demands for personal loyalty and his
      attempts to subjugate his followers to intellectual tyranny.

PMID- 19771686
TI  - Conversation with a Truth Seeker.
AB  - This paper is an invited response to Peter Rudnytsky's "Guardians of Truth"
      article. Taking issue with what are presented as fundamental theoretical and
      methodological caveats, this article discusses the question of when and how
      differing discourses on the history of psychoanalysis may or may not be
      compatible. In particular the author questions the validity of a concept of truth
      as defined from within a field of knowledge, to arrive at definitions of
      discourse and dialogue that can be useful to acquire new forms of knowledge.

PMID- 19771687
TI  - [Laboratory surveillance of drug resistance tuberculosis in Portugal in 2000
      2001].
AB  - BACKGROUND: A network for the Surveillance of Antituberculosis Drug Resistance
      (VigLab-Tuberculose), including all the mycobacterial laboratories where drug
      susceptibility test on isolates of Mycobacterium tuberculosis complex are carried
      out, was established in Portugal in April 2000. VigLab-Tuberculose aims to
      maintain a laboratory-based surveillance system for antibiotic susceptibilities
      of Mycobacterium tuberculosis complex isolates in order to monitor trends in drug
      resistance in Portugal. OBJECTIVE: To describe the first line antituberculosis
      drug resistance patterns of tuberculosis cases diagnosed and reported to VigLab
      Tuberculose in 2000-2001. METHODS: Collaborating laboratories collect and report
      data on individuals from whom a drug susceptibility test on Mycobacterium
      tuberculosis complex isolates has been performed in 2000-2001. Data collected
      included demographic, geographic, clinical and first line antibiotics
      susceptibility information. Data were analysed using Epi-Info version 6.04c
      software. RESULTS: There were 4170 reports of drug susceptibility test results on
      tuberculosis patients diagnosed from 1st April 2000 to 31st December 2001. Drug
      susceptibility results for all five first line antituberculosis drugs shows that
      23% (541/2358) were resistant at least to one of them. The proportion of mono
      resistance to streptomycin was 7,6% (179/2358), to isoniazid 2,6% (62/2358), to
      rifampicin 0,6% (15/2358) and to pyrazinamide 1,3% (30/2358). From the 4164
      patients tested both to isoniazid and rifampicina, 244 (5,9%) were multidrug
      resistant. From patients with no history of previous tuberculosis treatment, 1,8%
      (28/1557) were mono-resistant to isoniazid, 0,4% (7/1557) to rifampicina, 4,2%
      (66/1557) to streptomycin and 1,7% (27/1557) to pyrazinamide. The proportion of
      primary multidrug resistance was 2,8% (43/1557) and acquired resistance was 13,3%
      (41/309). CONCLUSION: The laboratory participation rate was 80%, which is very
      encouraging for the first two years of VigLab-Tuberculose activities. The
      proportion of primary multidrug resistance was higher than the reported
      resistance from central and west Europe (less 1%), which reinforce the need and
      importance of maintaining and strengthening the laboratory-based surveillance in
      order to minimise the emergence of drug resistance.

PMID- 19771688
TI  - [The Viriato Study: update of antimicrobial susceptibility data of bacterial
      pathogens from community-acquired respiratory tract infections in Portugal in
      2001 and 2002].
AB  - The Viriato Study is a nationwide, prospective, multicenter surveillance study of
      the antimicrobial susceptibility of bacterial pathogens commonly associated with
      community-acquired respiratory tract infections in Portugal. In years 2001 and
      2002, 31 laboratories participated in the study with a total of 2,600 strains,
      with testing undertaken in a central laboratory. Of the 486 Streptococcus
      pyogenes strains isolated from patients with acute tonsillitis all were
      susceptible to penicillin and other beta-lactams but 21.6% were resistant to
      erythromycin, clarithromycin and azithromycin. From patients with lower
      respiratory tract infection 1,071 strains of Streptococcus pneumoniae, 811 of
      Haemophilus influenzae, and 232 of Moraxella catarrhalis were studied. Among S.
      pneumoniae isolates 23% were resistant to penicillin (6.7% showing high-level
      resistance), 9.1% to cefuroxime, 1.0% to amoxycillin, 12.5% to erythromycin,
      clarithromycin and azithromycin, 10.9% to tetracycline, 29.8% to co-trimoxazol,
      and 3.0% to ofloxacin. Beta-lactamase was produced by 13.1% of H. influenzae and
      94.4% of M. catarrhalis. In H. influenzae resistance to clarithromycin was 12.5%
      and to co-trimoxazole 15%. Most strains were susceptible to
      amoxycillin/clavulanate, cefuroxime, azithromycin, tetracycline and
      ciprofloxacin. In M. catarrhalis resistance to co-trimoxazole was 25%. All
      strains were susceptible to amoxycillin/clavulanate, cefuroxime, clarithromycin,
      azithromycin, tetracycline and ciprofloxacin. As verified in previous years of
      the Viriato Study, penicillin was the most active antimicrobial against S.
      pyogenes and amoxycillin/clavulanate the most active in vitro simultaneously
      against H. influenzae, S. pneumoniae and M. catarrhalis isolated from patients
      with community-acquired lower respiratory tract infection in Portugal.

PMID- 19771689
TI  - [Drowning: tematic review and casuistic analysis in the Intensive Care Medicine
      Service of University Hospital of Coimbra (1989-2002)].
AB  - Drowning is a major cause of accidental deaths, especially in childrens. In this
      review (part one) the definition, epidemiology, pathophysiology and treatments
      (with an enphasis on the ressuscitation) are discussed. From 1989 to 2002 part
      two) we recorded the clinical course of the 19 patients vitims of submersion
      admited to our ICU. We conclued that the majority of patients are young (mean =
      37,3 years), mortality is high (26%), but the complete recovery is possible
      (63%). The cardio-respiratory arrest or Glasgow Coma Scale < or = 5 were related
      with poor prognosis, only with 3 survivors (1 without sequels). Trauma associated
      lesions were observed only in one patient.

PMID- 19771690
TI  - [Obstructive sleep apnoea and cardiovascular disease--a retrospective study].
AB  - INTRODUCTION: Obstructive Sleep Apnea (OSA) is associated with adverse effects in
      cardiovascular physiology. Some studies have connected this pathology with
      Cardiovascular Disease (CVD). AIM: Determine the prevalence of CVD in patients
      with OSA of different severity and verify the association between CVD and OSA.
      MATERIAL AND METHODS: Retrospective study based on data from 155 consecutive
      patients with OSA referred to a Sleep Disordered Breathing Clinic in an
      University Hospital during the year of 2001. RESULTS: The majority of patients
      were male (83,2%), the mean age was 53,6 +/- 11,9 years. Severe OSA was observed
      in 52,9% patients, moderate in 20% and mild in 27,1% patients (mean Apnea
      Hypopnea Index of 35,2 +/- 23,8/hour). Among the studied individuals 52,3% showed
      CVD, being Arterial Hypertension (AH) the most common disease (45,8%). Acute
      Myocardial Infarction appeared in 6,5% and Angina in 3,9% cases. The majority of
      the patients (67,1%) were obese (Body Mass Index - BMI>30). The mean BMI was 33,1
      +/- 6,34. A significant (31%) number of patients reported Lipid Disorders and 11%
      reported Diabetes mellitus. The majority (51,3%) of patients referred smoking
      habits. Severity of OSA (evaluated by AHI) was significantly higher in women with
      AH (p= 0,033) and significantly lower in patients who developed Cerebrovascular
      Disease (CeVD) (p = 0,036). CONCLUSIONS: The studied population presented a high
      prevalence of CVD, being the severity of OSA significantly higher in women with
      AH. The increased prevalence of CVD in patients with OSA has been documented in
      recent epidemiologic studies. The physiopathologic mechanisms underlying this
      association, certainly, deserve further investigation.

PMID- 19771691
TI  - [Epidemiological survey of bacteria isolated from the respiratory tract of cystic
      fibrosis patients].
AB  - With the aim of characterizing the evolution of the epidemiological profile of
      respiratory bacterial infections of patients having Cystic Fibrosis (CF), the
      authors conducted a retrospective analysis about it's incidence and prevalence in
      78 CF patients followed at the CF Specialized Centre, Paediatric Department,
      Santa Maria Hospital, Lisbon, during a 5 years period (1995-1999). Pseudomonas
      aeruginosa was the most frequently isolated bacteria during the first three years
      of the study (60-73%), being surpassed by Staphylococcus aureus. However,
      Pseudomonas aeruginosa always remained the principal agent of chronic
      colonization (44-59%), with a peak of beginning between 0 and 5 years (34%). A
      significative increase of the prevalence of intermitent and chronic colonization
      with Staphylococcus aureus was verified during this five years (48% to 83% and
      32% to 54%). The prevalence of isolations of Meticillin Resistant Staphylococcus
      aureus and of Burkholderia cepacia almost duplicated during this period. The
      taxes of isolation and chronic colonization with Alcaligenes xylosoxidans raised
      sharply beyond 1997 (from 3% and 0% in 1996 to 7% and 5% in 1997 and 10% and 7%
      in 1999). Chronic colonization with Haemophilus influenzae kept a median
      prevalence of 22%, in spite of an increase in isolations (from 42% to 61%). Fifty
      five per cent of the patients were chronically colonized by two or more agents.
      In view of these results, the authors discuss the therapeutic schemes and the
      measures to limit cross-infection which have been being advocated for CF patients
      in our centre.

PMID- 19771692
TI  - [Endocrine and metabolic manifestations in tuberculosis].
AB  - In the present paper, the authors reviews the endocrine and metabolic
      manifestations in tuberculosis. Disorders as adrenal insufficiency, the syndrome
      of inappropriate antidiuretic hormone secretion (SIADH), hypercalcemia, endocrine
      effects of antituberculous drugs, hypopituitarism, tuberculous involvement of the
      thyroid gland and pancreas and chest radiograph presentation in diabetes mellitus
      are discussed. In the literature, several reports support the presence of
      abnormal calcium metabolism in tuberculosis.

PMID- 19771693
TI  - Introduction: a special issue on electron diffraction.

PMID- 19771694
TI  - Quantitative convergent beam electron diffraction measurements of low-order
      structure factors in copper.
AB  - Accurate low-order structure factors for copper metal have been measured by
      quantitative convergent beam electron diffraction (QCBED). The standard deviation
      of the measured structure factors is equal to or smaller than the most accurate
      measurement by any other method, including X-ray single crystal Pendellosung,
      Bragg gamma-ray diffraction, and high-energy electron diffraction. The electron
      structure factor for the (440) reflection was used to determine the Debye-Waller
      (DW) factor. The local heating of the specimen by the electron beam is determined
      to be 5 K under the current illumination conditions. The low-order structure
      factors for copper measured by different methods are compared and discussed. The
      new data set is used to test band theory and to obtain a charge density map. The
      charge deformation map shows a charge surplus between the atoms and agrees fairly
      well with the simple model of copper 2+ ions at the atomic sites in a sea of free
      uniformly distributed electrons.

PMID- 19771695
TI  - Analysis of local strain in aluminum interconnects by convergent beam electron
      diffraction.
AB  - Energy filtered convergent beam electron diffraction was used to investigate
      localized strain in aluminum interconnects. By analyzing the position of higher
      order Laue zone lines, it is possible to measure the three-dimensional lattice
      strain with high accuracy (approximately 10(-4)) and high spatial resolution (10
      to 100 nm). In the present article, important details of the strain analysis
      procedure are outlined. Subsequently, results of measurements of the local
      variation of thermal strains in narrow, free-standing interconnects are
      presented. The strain development in single grains during thermal cycling between
      -170 degrees C and + 100 degrees C was measured in situ and local stress
      variations along the interconnect were investigated. The interconnects show
      reversible elastic behavior over the whole temperature range, leading to large
      stresses at low temperatures. The strain state varies locally within single
      grains, as well as from grain to grain, by as much as 50% in both types of
      samples. By comparing the experimental findings with elastic finite element
      modeling, a detailed understanding of the triaxial strain state could be
      achieved.

PMID- 19771696
TI  - Sufficient conditions for Direct Methods with swift electrons.
AB  - We investigate cases where one can argue that sufficient conditions exist for
      Direct Methods to work with swift electrons. In addition to simple cases where
      kinematical scattering holds (e.g., surfaces in plan view), we identify three
      other configurations: (a) when 1s channeling holds and kinematical scattering is
      statistically correct; (b) when there is a mapping from kinematical to dynamical
      intensities that preserves the order of the intensities, for instance with powder
      or precession data, and (c) when the scattering is dominated by one type of atom.
      We also briefly discuss the possibility of using Direct Methods to restore the
      complex exit wave leaving a sample in the most general case.

PMID- 19771697
TI  - Quantitative zone-axis convergent beam electron diffraction: current status and
      future prospects.
AB  - Quantitative zone-axis convergent beam electron diffraction (CBED) is now an
      established technique. Over the past decade it has been developed into a tested
      method for the accurate refinement of structure factors, allowing the details of
      the charge density and bonding effects to be studied in crystalline materials.
      Strategies for obtaining the most accurate results have evolved, and the most
      important influences on the accuracy have been determined. Initial applications
      of the technique to bond charge density determination have led to the extension
      of the method to the refinement of other important parameters influencing the
      experimental data, such as Debye-Waller factors and the absorption potential. The
      development and current status of quantitative zone-axis CBED are discussed.
      Prospects for the future development and application of the technique are also
      considered.

PMID- 19771698
TI  - A combination method of charge density measurement in hard materials using
      accurate, quantitative electron and X-ray diffraction: the alpha-Al2O3 case.
AB  - Current X-ray diffraction techniques intended for "ideally imperfect" specimens
      provide structure factors only on a relative scale and ever-present multiple
      scattering in strong low-angle Bragg reflections is difficult to correct.
      Multiple scattering is implicit in the quantitative convergent beam electron
      diffraction (QCBED) method, which provides absolutely scaled structure factors.
      Conventional single crystal X-ray diffraction has proved adequate in softer
      materials where crystal perfection is limited. In hard materials, the highly
      perfect nature of the crystals is often a difficulty, due to the inadequacy of
      the conventional corrections for multiple scattering (extinction corrections).
      The present study on alpha-Al2O3 exploits the complementarity of synchrotron X
      ray measurements for weak and medium intensities and QCBED measurement of the
      strong low-angle reflections. Two-dimensional near zone axis QCBED data from
      different crystals at various accelerating voltages, thicknesses, and
      orientations have been matched using Bloch-wave and multislice methods. The
      reproducibility of QCBED data is better than 0.5%. The low-angle strong QCBED
      structure factors were combined with middle and high-angle extinction-free data
      from synchrotron X-ray diffraction measurements. Static deformation charge
      density maps for alpha-Al2O3 have been calculated from a multipole expansion
      model refined using the combined QCBED and X-ray data.

PMID- 19771699
TI  - Low-dose, low-temperature convergent-beam electron diffraction and
      multiwavelength analysis of hydrocarbon films by electron diffraction.
AB  - Aromatic hydrocarbon (perylene, coronene) and tetracontane films are shown to
      produce useful convergent-beam electron diffraction (CBED) patterns under low
      dose and low-temperature conditions. These were obtained using a Zeiss LEO-921
      electron microscope with an omega energy filter at liquid helium and nitrogen
      temperatures. The usefulness of patterns showing CBED disks of constant intensity
      ("blank disks," indicating kinematic scattering) for structure analysis is
      investigated, with the aim of avoiding film-bending artifacts. Using CBED
      patterns from thicker areas, sample thickness was experimentally determined using
      either two-beam or three-beam patterns. Koehler mode illumination (a new form of
      SAD pattern offering smaller areas) was also used, and the possibility of
      obtaining structure factor moduli using the kinematic and two-beam approximations
      was investigated by comparing measured diffraction intensities with experimental
      ones for these known structures. The commonly used approximation [F]
      approximately I(g) (intended to account for bending) was found to be a worse
      approximation than the two-beam approximation with well-defined excitation error
      for these microdiffraction experiments. A new multiwavelength method of
      retrieving structure factor moduli and thickness from microdiffraction patterns
      using two-beam theory is demonstrated for tetracontane.

PMID- 19771700
TI  - Accurate measurements of valence electron distribution and interfacial lattice
      displacement using quantitative electron diffraction.
AB  - We developed a novel electron-diffraction technique by focusing a small probe
      above (or below) the sample in an electron microscope to measure charge density
      and lattice displacement in technologically important materials. The method
      features the simultaneous acquisition of shadow images within many Bragg
      reflections, resulting in parallel recording of dark-field images (PARODI).
      Because it couples diffraction with images, it is thus suitable for studying
      crystals as well as their defects. We used this technique to accurately locate
      the charge-carrying holes in superconducting crystals, and to determine
      displacement vectors across planar faults by comparing the experiments with
      calculations, and by using fitting and error analyses. Examples are given for
      complex YBa2Cu3O7 and Bi2Sr2CaCu2O8+delta oxides and the newly discovered MgB2
      superconductor.

PMID- 19771701
TI  - On the consistency of QCBED structure factor measurements for TiO2 (rutile).
AB  - The same Bragg reflection in TiO2 from 12 different (CBED) patterns (from
      different crystals, orientations, and thicknesses) are analyzed quantitatively to
      evaluate the consistency of the quantitative CBED method for bond-charge mapping.
      The standard deviation in the resulting distribution of derived X-ray structure
      factors is found to be an order of magnitude smaller than that in conventional X
      ray work, and the standard error (0.026% for F(x)(110)) is slightly better than
      obtained by the X-ray Pendellosung method applied to silicon. This is
      sufficiently accurate to distinguish between atomic, covalent, and ionic models
      of bonding. We describe the importance of extracting experimental parameters from
      CCD camera characterization, and of surface oxidation and crystal shape. The
      current experiments show that the QCBED method is now a robust and powerful tool
      for low-order structure factor measurement, which does not suffer from the large
      extinction (multiple scattering) errors that occur in inorganic X-ray
      crystallography, and may be applied to nanocrystals. Our results will be used to
      understand the role of d-electrons in the chemical bonding of TiO2.

PMID- 19771702
TI  - A quantitative nanodiffraction system for ultrahigh vacuum scanning transmission
      electron microscopy.
AB  - Of all the long-lived particles available as probes of condensed matter, and of
      all the signals available on a modern electron microscope, electron
      nanodiffraction patterns provide the strongest signal from the smallest volume.
      The technique is therefore perfectly suited to nanostructural investigations in
      inorganic chemistry and materials science. The Vacuum Generators HB501S, an
      ultrahigh vacuum (UHV) variant of the HB501 scanning transmission electron
      microscope (STEM), with side-entry double-tilt stage, specimen preparation and
      analysis chamber, three postspecimen lenses, and cold field-emission tip with
      integral magnetic gun lens, has therefore been modified to optimize
      nanodiffraction and quantitative convergent beam electron diffraction (QCBED)
      performance. A one-micrometer grain-size phosphor screen lying on a fiber-optic
      faceplate atop the instrument is fiber-optically coupled to a 2048 x 2048 charge
      coupled device (CCD), 16-bit camera. This arrangement promises to provide much
      greater sensitivity, larger dynamic range, and a better modulation transfer
      function (MTF) than conventional single crystal scintillator (YAG) CCD systems,
      with noticeable absence of cross talk between pixels. The design of the
      nanodiffraction detector system is discussed, the gain of the detector is
      measured, the spherical aberration constant of the objective lens is measured by
      the Ronchigram method, and preliminary results from the modified instrument are
      shown.

PMID- 19771703
TI  - Quantitative electron diffraction evidence for one-dimensional ordering in
      magnetite above the Verwey transition.
AB  - Energy-filtered electron diffraction and three-dimensional reciprocal lattice
      mapping was used to study the nature of diffuse scattering in magnetite above the
      Verwey transition temperature. Characteristic Huang scattering associated with a
      single molecular polaron is observed at room temperature. As the temperature is
      lowered, the experiment shows narrowing of diffuse scattering in the (001)
      directions and additional ringlike diffuse scattering at q approximately 0.8,
      which suggests the presence of one-dimensional structures above the Verwey
      transition. Experimental measurements of temperature-dependent correlation
      lengths and diffuse scattering intensity indicate an increase in the number and
      length of the one-dimensional structure as the temperature is cooled toward the
      transition. This study demonstrates the electron sensitivity to atomic
      displacement and the quality of electron diffraction data for studying phase
      transition in complex materials.

PMID- 19771704
TI  - Issues in estimating the prevalence of intimate partner violence: assessing the
      impact of abuse status on participation bias.
AB  - This study examines the potential implications of household interviews on
      participation bias for estimates of intimate partner violence (IPV). Using a
      variety of scales, IPV prevalence for the 135 women interviewed in a street
      intercept survey was compared with the IPV prevalence of a subsample of these
      women who reported willingness to participate in a household survey with their
      partner in another room or when their partner also would be interviewed. A
      potential self-selection bias showed an 8% to 13% deflated prevalence of moderate
      to highly abused women and a 8% to 11% inflated prevalence of nonabused women
      among this subsample who would willingly participate in a household survey.
      Understanding who is included in household surveys, and who is not, is essential
      to compute and interpret national prevalence estimates for IPV.

PMID- 19771705
TI  - The structure and content of verbal and physical aggression among Israeli youths.
AB  - The aim of this study is to test an aggression model. Data were obtained from 943
      students in the 7th, 8th, and 9th grades of junior high schools in a northern
      Israeli city and its suburbs. A structural equation model analysis confirmed that
      there is a significant positive correlation between the constructs of perception
      (i.e., aggressor and aggression), means (i.e., behavioral and emotional
      capabilities), and guidelines (i.e., scripts) and that behavioral performance
      (i.e., aggressive or nonaggressive behavior) is influenced significantly only by
      guidelines and means. In addition, it was found that boys and younger youths tend
      to present higher levels of aggressiveness across all constructs as compared to
      girls and older youths. Theoretical and practical implications are discussed.

PMID- 19771706
TI  - Proclivity to elder abuse: a community study on Hong Kong Chinese.
AB  - This study aimed to provide preliminary estimates on proclivity to elder abuse
      and to determine the efficacy of the intergenerational transmission of violence
      and ecological theories in predicting elder abuse in contemporary Chinese
      societies. A total of 464 (225 males and 239 females) Chinese residing in Hong
      Kong completed questionnaires on attitudes toward elderly people, modernity, and
      filial piety as well as childhood experiences of abuse and proclivity to elder
      abuse. Results indicated that proclivity to verbal elder abuse was the most
      common among the three depicted types of abuse, accounting for 20% of the sample,
      whereas proclivity to physical and social elder abuse was less common, each
      accounting for 2.4%. A high level of childhood experience of abuse consistently
      emerged as the single most salient predictor for participants' endorsement of
      proclivity to elder abuse, while negative attitudes toward elderly people and
      modernity were the second and third most salient predictors.

PMID- 19771707
TI  - Behavioral indicators of sadistic sexual murder predict the presence of sadistic
      sexual fantasy in a normative sample.
AB  - Burgess, Hartman, Ressler, Douglas, and McCormack noted a high prevalence of
      certain behavioral and experiential characteristics in sexual murderers and
      argued for their etiological importance. The present study aimed to measure the
      prevalence of these indicators in a nonoffending control population and to
      evaluate whether they identified sadistic sexual fantasy. The prevalence of
      behavioral and experiential indicators and degree of sadistic sexual interest
      were measured in 50 healthy nonoffenders. Compared to Burgess et al.'s sexual
      murderers, higher prevalence levels for most experiential indicators were found,
      whereas many of the behavioral indicators were less prevalent. Three of the
      behavioral indicators were significantly associated with the presence of sadistic
      sexual fantasies. The presence of behavioral indicators that predict sadistic
      sexual fantasy confirms the importance of these factors in the etiology of the
      development of sadistic sexual fantasy in both offenders and nonoffenders and may
      be useful in risk assessment.

PMID- 19771708
TI  - The impact of partner psychological abuse on health behaviors and health status
      in college women.
AB  - Previous research documents increased health problems, somatic complaints, and
      negative health behaviors among victims of physical and sexual violence. This
      study extended existing literature by examining the unique effects of partner
      psychological abuse on physical health and the moderating effects of approach and
      avoidance coping strategies. Psychological abuse was positively related to
      illegal drug use, physical and role limitations, negative health perceptions, and
      cognitive impairment in college women even after controlling for physical
      victimization. Psychological abuse was not related to sleep hygiene, exercise,
      problem drinking, or smoking. Approach coping moderated the effects of partner
      psychological abuse on binge drinking and health perceptions. Low approach coping
      was associated with more binge drinking and negative health perceptions as abuse
      increased; high approach coping did not show a significant relationship with
      binge drinking or health perceptions across levels of abuse. Avoidance coping
      showed only a trend as a moderator of illegal drugs.

PMID- 19771709
TI  - Bystanders' perceptions of perpetrators and victims of hate crime: an
      investigation using the person perception paradigm.
AB  - This study used the person perception vignette method to examine whether people
      perceive hate crime victims as more culpable than non-hate crime victims. In a
      between-participants design, participants were randomly assigned to read a
      vignette depicting a nonhate crime or a comparable hate crime motivated by the
      perpetrator's hatred for either the victim's race, sexual orientation, or
      religion. Results showed that participants assigned more blame to the victim in
      the non-hate crime condition compared to the victims in each of the three hate
      crime conditions. In addition, they perceived the perpetrators as more guilty in
      each of the three hate crime conditions compared to the non-hate crime condition.
      In addition, people with prejudiced attitudes perceived both hate crime and non
      hate crime victims as more culpable and both hate crime and non-hate crime
      perpetrators as less culpable than did unprejudiced people.

PMID- 19771710
TI  - Level of Service Inventory-Revised profiles of violent and nonviolent prisoners.
AB  - Level of Service Inventory-Revised (LSI-R) assessments were conducted on 251 male
      prisoners beginning prison sentences in six English prisons. The prisoners who
      were classified as violent, on the basis of either current or previous
      convictions, scored significantly higher than the nonviolent prisoners on the
      four LSI-R subscales of Criminal History, Companions, Education and Employment,
      and Alcohol and Drugs. In addition, those prisoners with a record of violent
      offenses gave higher total LSI-R scores, indicating an overall higher risk of
      recidivism. Multivariate analysis using the LSI-R subscales to classify the
      higher risk violent prisoners and minimum-risk nonviolent prisoners basically
      confirmed the findings of the univariate analysis. The implications of the
      findings for informing practice with violent offenders are discussed in terms of
      screening for intensity of service delivery and identification of targets for
      change. It is suggested that screening for drug and alcohol problems should be a
      prerequisite to working with violent offenders.

PMID- 19771711
TI  - A prognostic indicator scale for the treatment of partner abuse perpetrators.
AB  - This study examined prognostic indicators for violence recidivism among male
      domestic abuse perpetrators (N = 95). Seventeen hypothesized prognostic
      indicators were selected from baseline self-report and collateral partner report
      data to assess aggression history, psychoactive substance use, severity of
      relationship abuse problems, and current demographic factors. A total prognostic
      index, labeled the Partner Abuse Prognostic Scale (PAPS), predicted outcome
      variables derived from both victim report and criminal justice data and provided
      unique prediction relative to a pretreatment continuous measure of relationship
      violence. No moderator effects in prediction were observed across two distinct
      types of group treatment. Psychological aggression was the only pretreatment
      variable that consistently added significant prediction of recidivism beyond the
      PAPS. The PAPS is recommended for research uses involving statistical control or
      balancing of conditions in studies of partner violence interventions. Further
      research will be needed to establish cutoffs for clinical case management and
      treatment planning.

PMID- 19771712
TI  - Reductions in marital violence following treatment for alcohol dependence.
AB  - The impact of an intensive, individually based, partial hospitalization treatment
      for alcohol dependence on alcohol use, marital violence, psychological abuse, and
      marital satisfaction among 24 heterosexual male patients and their partners was
      assessed. Patients received 5 to 6 days of substance abuse treatment in a partial
      hospital. Patient and partner assessments were conducted at baseline and 6- and
      12-month follow-up. Results revealed decreased alcohol use in patients and
      significant declines in husband-to-wife marital violence and psychological abuse
      from baseline to 6- and 12-month follow-up. Men reported no significant changes
      in their marital satisfaction. Results also showed significant decreases in wife
      to-husband violence from baseline to 6- and 12-month follow-up. Female partners
      reported a significant increase in marital satisfaction from baseline to 6- and
      12-month follow-up. Overall, the study suggests that marital violence perpetrated
      by male patients and their partners declined following the males' substance abuse
      treatment. The clinical implications of the findings are discussed.

PMID- 19771713
TI  - Attitudes supporting violence and aggressive behavior among adolescents in
      Israel: the role of family and peers.
AB  - A secondary analysis of data obtained from a national representative sample of
      the adolescent population in Israel was conducted to explore the association
      between the quality of social relationships of adolescents and aggressive
      behavior. The quality of parent-adolescent relations and the quality of peer
      relations were not directly related to aggressive behavior. Adolescents who were
      close to their parents and their peers were less likely to report exposure to
      negative relations with other adolescents. Adolescents who reported being
      insulted held attitudes favoring the use of aggressive behavior, associated more
      with delinquent adolescents, and reported a high level of aggression toward
      others. Adolescents who did not share intimate communication with significant
      others tended to be more exposed to unpleasant behavior to associate with
      delinquent peers, and to adopt aggressive attitudes and behaviors. The results
      suggest that experiencing negative relations during adolescence might be a risk
      factor predicting aggressive conduct.

PMID- 19771714
TI  - The effects of father visitation on preschool-aged witnesses of domestic
      violence.
AB  - Fifty preschool children with varying amounts of visitation with their previously
      violent fathers were studied to determine if the amount of father visitation was
      related to their behavioral functioning. The possible association of the severity
      of violence witnessed and the quality of the mother-child relationship on child
      behaviors was also assessed. There was a significant negative relationship
      between internalizing and externalizing behaviors, as measured by the Child
      Behavior Checklist, and frequency of father visitation. Children who saw their
      fathers less frequently evidenced higher internalizing and externalizing scores.
      More severe levels of violence perpetrated by the father significantly predicted
      increased externalizing behavior scores but not internalizing scores. Severity of
      violence was more predictive of externalizing behaviors than frequency of father
      visitation.

PMID- 19771715
TI  - Nonfamily child abductors who murder their victims: offender demographics from
      interviews with incarcerated offenders.
AB  - Nonfamily child abductions have a low rate of occurrence despite the media
      attention and public hysteria that these types of cases often attract. Although
      the annual incident rate is low, nonfamily child abductions are emotionally
      charged crimes that can rapidly overwhelm law enforcement resources. The 24-hour
      period following an abduction is critical, and law enforcement must be prepared
      to respond immediately and effectively. The purpose of the present research is to
      obtain demographic and background history on convicted nonfamily child abductors
      who have murdered their victims. Data for the study were obtained through
      interviews of incarcerated offenders and review of case documents. To date,
      interviews with 25 child abductors who murdered their victims have been conducted
      within various prison facilities.

PMID- 19771716
TI  - Examining the link between child abuse and youth violence: an analysis of
      mediating mechanisms.
AB  - This study investigates several factors as possible mediators of physical child
      abuse in the prediction of violence among adolescents. Prospective and
      retrospective measures of abuse are compared in mediation tests. Data are from
      the Lehigh Longitudinal Study, a prospective study of 457 children followed from
      preschool into adolescence. Structural equation models examined the degree to
      which abuse is mediated in the prediction of violence through youths' bonds to
      family, commitment to school, involvement with antisocial peers during
      adolescence, and attitudes about the use of violence. The model included measures
      of family socioeconomic status and youths' gender and age as controls on
      violence. Findings suggest that abuse (whether measured prospectively or
      retrospectively) is heavily mediated in its prediction of later violence and that
      a sizeable proportion of variance is accounted for in the violence outcome. A
      fuller pattern of mediation was shown when the retrospective abuse variable was
      modeled.

PMID- 19771717
TI  - Base rates of hate crime victimization among college students.
AB  - This study uses the unmatched count technique (UCT) to estimate base rates for
      hate crime victimization in college students and compares the results with
      estimates found using conventional methods. Hate crimes, criminal acts
      perpetrated against individuals or members of specific stigmatized groups, intend
      to express condemnation, hate, disapproval, dislike, or distrust for a group. The
      UCT is a promising tool in the investigation of hate crime because it does not
      require participants to directly answer sensitive questions. This may provide
      more accurate responses than other methods. The UCT revealed higher estimates for
      a variety of serious hate crimes, including physical and sexual assault. These
      higher estimates provide a better feel for the level of hate crime victimization
      and point to the increased need for hate crime victims' assistance programs on
      college campuses.

PMID- 19771718
TI  - Gender differences in sexual harassment and coercion in college students:
      developmental, individual, and situational determinants.
AB  - Differences in male (N = 148) and female (N = 278) college students' use of
      sexually harassing and coercive behaviors were investigated. Men were twice as
      likely to be sexually harassing and 3 times more likely to be sexually coercive
      as women. Among men, sexual harassment was predicted by child sexual abuse,
      hostility, adversarial heterosexual beliefs, and alcohol expectancy, with the
      latter mediating the effects of aggression. Sexual coercion was predicted by
      adult sexual victimization and alcohol expectancy, with alcohol expectancy again
      mediating the effect of aggression. Among women, sexual harassment was predicted
      by adult sexual victimization, adversarial heterosexual beliefs, aggression, and
      alcohol expectancy, with aggression mediating the effect of adversarial
      heterosexual beliefs and alcohol expectancy mediating the effect of aggression.
      Sexual coercion was predicted by a hostile personality, which mediated the
      effects of both child and adult sexual victimization. These findings suggest both
      gender similarities and differences in determinants of sexual aggression.

PMID- 19771719
TI  - Costs of complementary and alternative medicine (CAM) and frequency of visits to
      CAM practitioners: United States, 2007.
AB  - OBJECTIVE: This report presents selected estimates of costs of complementary and
      alternative medicine (CAM) use among U.S. adults, the frequency of visits made to
      CAM providers, and the frequency of purchases of self-care CAM therapies. Data
      from the 2007 National Health Interview Survey (NHIS), which is conducted by the
      Centers for Disease Control and Prevention's National Center for Health
      Statistics, are used in this report. METHODS: Estimates were derived from the
      Complementary and Alternative Medicine Supplement of the 2007 NHIS, sponsored by
      the National Center for Complementary and Alternative Medicine, which is part of
      the National Institutes of Health. Estimates were generated using the SUDAAN
      statistical package to account for the NHIS complex sample design. RESULTS: In
      2007, adults in the United States spent $33.9 billion out of pocket on visits to
      CAM practitioners and purchases of CAM products, classes, and materials. Nearly
      two-thirds of the total out-of-pocket costs that adults spent on CAM were for
      self-care purchases of CAM products, classes, and materials during the past 12
      months ($22.0 billion), compared with about one-third spent on practitioner
      visits ($11.9 billion). Despite this emphasis on self-care therapies, 38.1
      million adults made an estimated 354.2 million visits to practitioners of CAM.
      About three-quarters of both visits to CAM practitioners and total out-of-pocket
      costs spent on CAM practitioners were associated with manipulative and body-based
      therapies. A total of 44% of all out-of-pocket costs for CAM, or about $14.8
      billion, was spent on the purchase of nonvitamin, nonmineral, natural products.

PMID- 19771720
TI  - [Chemotherapy of tuberculosis and its challenges].
AB  - Tuberculosis (TB), a chronic communicable disease, continues to be a global
      public health concern. Slow decline of TB incidence and prevalence, human
      immunodeficiency virus/TB coinfection, growth of multidrug-resistant/extensively
      resistant TB have made the control of TB even more challenging. Chemotherapy of
      TB has developed for decades and now also faces similar challenges.

PMID- 19771721
TI  - [Prevention and control of tuberculosis in China].
AB  - Tuberculosis (TB) is one of the global major public health problems. China has
      the second highest TB burden worldwide. This article introduces the epidemiology
      of TB in China and elucidates the progress and challenges in TB prevention and
      control.

PMID- 19771722
TI  - [Prokaryotic expression, purification, and immunogenicity analysis of
      Mycobacterium tuberculosis specific excretive proteins].
AB  - OBJECTIVE: To obtain the recombinant rv1837c and rv3803c of Mycobacterium
      tuberculosis using gene engineering technology and explore their prokaryotic
      expression, purification, and immunogenicity. METHODS: The Mycobacterium
      tuberculosis rv1837c and rv3803c genes were amplified by polymerase chain
      reaction, and then cloned into the vector pTA2, followed by the subclone into the
      expression vector pET30a (+). The resulting plasmids, named pET30a (+): rv1837c
      and pET30a (+): rv3803c, encode recombinant protein containing a hexa-histidine
      tag on its N-terminus. pET30a (+): rv1837c and pET30a (+): rv3803c were
      introduced into E. coli BL21 (DE3) by transformation respectively, and the
      recombinant gene was induced with 0.4 mmol/L isopropyl-D-thiogalactopyranoside.
      The expressed products were identified by Western blot with hexa-histidine tag
      antibody and serum from tuberculotic patients. The histidine tagged protein was
      purified by nickel nitrilotriacetic acid His-Bind resin. Rabbits were immunized
      with purified recombinant Rv1837c and Rv3803c proteins. Then the purified
      recombinant Rv1837c and Rv3803c proteins were used to detect antibody in rabbit
      serum, which had been immunized by Western blot. RESULTS: After transformation of
      the E. coli and induction with 0.4 mmol/L of isopropyl-D-thiogalactopyranoside,
      recombinant target proteins Rv1837c (relative molecular mass: 92000) and Rv3803c
      (relative molecular mass: 38 000) were expressed in pET30a (+): rv1837c and
      pET30a (+): rv3803c system. The expressed protein existed in cytoplasm in an
      unsoluble form and amounted to 30% and 50% of the total proteins of E. coli. The
      purity of the purified protein reached 90%. The immunogenicity of the recombinant
      proteins Rv1837c and Rv3803c was strong, as identified by Western blot.
      CONCLUSION: The prokaryotic expression recombinant plasmids pET30a (+): rv1837c
      and pET30a (+): rv3803c was successfully constructed and the recombinant proteins
      Rv1837c and Rv3803c were obtained, which laid a basis for the optimized diagnosis
      of active tuberculosis.

PMID- 19771723
TI  - [Preparation of two antigens--Ag85b and HspX of Mycobacterium tuberculosis H37Rv
      and the effects of their co-administration with adjuvants in mice].
AB  - OBJECTIVE: To synthesize two antigens-Ag85b and HspX of Mycobacterium
      tuberculosis H37Rv with molecular biological methods and to observe their
      biologic activity after co-administration of adjuvants (aluminum and/or CpG) in
      mice. METHODS: Recombinant expression plasmids pET30a-Ag85b and pET30a-HspX were
      constructed. The objective DNA fragments was characterized with restriction
      enzyme. Then the recombinant plasmids were transformed into E. coli BL-21, and
      two proteins were expressed by induction of isopropyl beta-D-1
      thiogalactopyranoside. After purification with anion exchange column Source30,
      QHP, and hydrophobic chromatography column, two proteins were identified by amino
      acid sequencing. After the successful preparation of these two antigens, they
      were co-administered in mice with adjuvants of aluminum and/or CpG (Ag85b, Ag85b
      + Al, Ag85b + CpG, Ag85b + Al + CpG; HspX, HspX + Al, HspX + CpG, HspX + Al +
      CpG); one group received normal saline and served as the control. Splenic
      lymphocytes were isolated for enzyme-linked immunosorbent spot assay to detect
      the secreted specific interferon-gamma (IFN-gamma); in addition, lymphocytes
      proliferation test was performed to observe lymphocytes proliferation after in
      vitro stimulated with two antigens. RESULTS: The purity of two proteins reached
      95% after purification. The N-terminal amino acid sequence (15 aa) of the
      purified proteins was same as the target sequence. For Ag85b, the secreted
      specific IFN-gamma from isolated splenic lymphocytes after having been stimulated
      in vitro with Ag85b (80 microg/ml) remarkably increased in Ag85b + CpG group,
      Ag85b + Al group, and Ag85b + CpG + Al group; the changes were significantly
      different between these three groups and control group (P < 0.05). For HspX, the
      changes were significantly different between HspX + Al + CpG group and normal
      sodium group, although remarked increase of IFN-gamma was also observed in HspX
      group, HspX + Al group, and HspX + CpG group. CONCLUSIONS: Ag85b and HspX were
      successfully expressed and purified. A cell-mediated immunity may be induced when
      the antigens are co-administered with adjuvants of aluminum and/or CpG in mice,
      indicating that the recombinant proteins are bioactive.

PMID- 19771724
TI  - [Effect of Mycobacterium smegmatis vaccine on the level of nitric oxide produced
      by peritoneal macrophages in mice].
AB  - OBJECTIVE: To study the effect of Mycobacterium smegmatis vaccine on the level of
      nitric oxide (NO) produced by peritoneal macrophages in immunized mice. METHODS:
      Balb/c mice were randomized into low-dose, middle-dose, and high-dose groups
      (injected with different doses of Mycobacterium smegmatis vaccine) and a control
      group (injected with normal saline). Then the peritoneal macrophages were
      cultured with lipopolysaccharide in vitro. The supernatants were collected and
      the concentrations of NO were analyzed through the reaction with Griess reagents.
      RESULTS: The levels of NO produced by the peritoneal macrophages in the control
      group, low-dose group, middle-dose group, and high-dose group were (3.50 +/-
      3.11), (16.63 +/- 6.47), (13.97 +/- 6.20), and (7.55 +/- 2.26) ng/ml,
      respectively. The levels of NO in all dosing groups were significantly different
      from that in control group (P < 0.01). CONCLUSION: Mycobacterium smegmatis
      vaccine can promote the peritoneal macrophages to produce NO in mice.

PMID- 19771725
TI  - [Establishment and evaluation of nitrate reductase combined with
      mycobacteriophage assay].
AB  - OBJECTIVE: To establish a rapid, inexpensive, and simple drug susceptibility test
      (DST) for Mycobacterium tuberculosis (M. tb) and evaluate its feasibility.
      METHOD: We used nitrate reductase combined with mycobacteriophage assay (PhaB
      NRA) to test 49 clinical M. tb isolates of, and the results were compared with
      those of PhaB-NRA and traditional absolute concentration method. RESULTS: The
      sensitivity, specificity, and accuracy of PhaB-NRA for rifampicin were 89.1%,
      91.67%, and 89.8%; on the contrary, those of isonicotinyl hydrazide were 86.21%,
      90.0%, and 87.8%, respectively. The coincidence between PhaB-NRA and traditional
      assay were 0.746 for rifampicin and 0.750 for isonicotinyl hydrazide.
      CONCLUSIONS: PhaB-NRA is an inexpensive, rapid, and simple DST method. It is a
      promising rapid screening technique for DST of M. tb.

PMID- 19771726
TI  - [Influences of Mycobacterium tuberculosis on the levels of human acute monocytic
      leukemia cell line THP-1 apoptosis and death].
AB  - OBJECTIVE: To explore the influences of Mycobacterium tuberculosis on the levels
      of human acute monocytic leukemia cell line THP-1 apoptosis and death. METHODS:
      Human acute monocytic leukemia cell line THP-1 were infected with Mycobacterium
      tuberculosis strains H37Ra, H37Rv, or Beijing genotype (BJTB), respectively, to
      construct the infection models. Cell apoptosis was detected using flow cytometry.
      The distribution of the apoptotic proteins was detected using immunofluorescent
      staining assays. The cells late apoptosis was detected using terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling staining assays. The
      change of cell death was determined by Tyrpan blue staining assays. RESULTS: THP
      1 apoptosis was induced by Mycobacterium tuberculosis strains H37Ra, H37Rv, and
      BJTB. H37Ra strongly induced THP-1 apoptosis, H37Rv weakly induced THP-1
      apoptosis, and BJTB induced THP-1 apoptosis at the lowest level among these three
      Mycobacterium tuberculosis strains. On the contrary, BJTB strongly induced THP-1
      death, H37Rv weakly induced THP-1 death, and H37Ra induced THP-1 death at the
      lowest level. CONCLUSIONS: Mycobacterial strains with different virulence induce
      different levels of apoptosis and death of THP-1 cells. Compared with highly
      virulent strains, attenuated strains induce more apoptosis and less death.

PMID- 19771727
TI  - [Relationship between the resuscitation promoting role of resuscitation promoting
      factor and the initial bacteria amount of dormant Mycobacterium tuberculosis].
AB  - OBJECTIVE: To investigate the relationship between the resuscitation promoting
      role of resuscitation promoting factor and the initial bacteria amount of dormant
      Mycobacterium tuberculosis. METHODS: Mycobacterium tuberculosis (dormant
      bacteria) was cultured for 100 days, then diluted into 1 mg/ml concentration with
      7H9, and further diluted into 0.5, 0.25, 0.125, 0.0625, and 0.03125 mg/ml. Twelve
      new tubes added with 5 ml 7H9 and divided into two groups: the first group was
      added with the resuscitation-promoting factor protein, and the second group as
      control was added with 7H9. In each group the above diluted solutions were added.
      The tubes were located at 37 degrees C for culture. Optical density (OD) was
      detected on day 15, 25, 30, and 35. From each tube 1 microl culture solution was
      plated on 7H11 medium for colony counting. RESULTS: OD detection showed that
      bacteria proliferation in each group had positive linear correlation (P < 0.05, P
      < 0.01), indicating that the resuscitation-promoting factor played a similiar
      role in solutions with different dilution concentrations. 7H11 results and the OD
      results show that these two detection methods in each group had linear
      correlation (P < 0.05, P < 0.01), indicating that these two methods showed
      consistent test results. CONCLUSION: The resuscitation-promoting factor has no
      effect on the resuscitation of dormant Mycobacterium tuberculosis and its initial
      bacteria amount.

PMID- 19771728
TI  - [Relationship between Beijing genotypes of Mycobacterium tuberculosis and drug
      resistant phenotypes].
AB  - OBJECTIVE: To investigate the distribution of the Beijing genotypes of
      Mycobacterium tuberculosis (M. tuberculosis) and the relationships between
      Beijing genotype strains and drug-resistant phenotypes in China. METHODS:
      Clinical isolates were collected during a 9-month research period from April to
      December in 2008 in six geographic regions of China. One isolate that had been
      biochemically confirmed to be a member of the M. tuberculosis complex was
      collected from each patient. The demographic data of the patients (eg. sex, age,
      and history of tuberculosis) as well as the drug resistance patterns and sources
      of the clinical isolates were collected. Drug susceptibility testing was
      performed using proportion method. Beijing genotypes of M. tuberculosis were
      identified by spacer oligonucleotide typing or insertion of IS6110 in the genomic
      dnaA-dnaN locus. RESULTS: Among the 410 M. tuberculosis clinical isolates, 67.1%
      (275/410) isolates were Beijing genotypes of M. tuberculosis. Significantly
      larger proportions of tuberculosis patients were infected with Beijing genotypes
      in the northeastern regions of China than that of in the central-western regions
      (chi2 = 20.50, P = 0.000). No significant associations were found either between
      Beijing genotype strains and patients' age, sex, or treatment history. Multidrug
      resistant isolates and rifampin-resistant isolates were more common among Beijing
      genotype strains than among non-Beijing strains (P = 0.002, P = 0.005).
      CONCLUSIONS: About two third of the clinical isolates of M. tuberculosis in China
      are Beijing genotypes. Beijing genotype strains are not correlated with patients'
      age, sex, treatment history. People living in the northeastern regions of China
      are more susceptible to Beijing genotypes than those living in the central
      western of China. Beijing genotype strains tend to be rifampin-resistant or
      multidrug-resistant.

PMID- 19771729
TI  - [Influences of intervention on the abilities of detecting pulmonary tuberculosis
      cases in general hospitals].
AB  - OBJECTIVE: To explore the influences of intervention on the abilities of
      detecting pulmonary tuberculosis cases in general hospitals. METHODS: We selected
      6 general hospitals at 3 different levels (A, B, and C). The intervened group
      included hospitals A1, B1, and C1, and the non-intervened group included
      hospitals A2, B2, and C2. The results after intervention were compared. RESULTS:
      The report rate of pulmonary tuberculosis, sputum positive rate of reported
      cases, and sputum check rate of reported cases were significantly higher in
      hospital A1 than grouping hospital A2 (P = 0.000, P = 0.045, and P = 0.017,
      respectively). The report rate and sputum examination rate of reported cases were
      significantly higher in hospital B1 than grouping hospital B2 (P = 0.000, P =
      0.024, respectively). The report rate and sputum examination rate of reported
      cases were significantly lower in hospital C1 than grouping hospital C2 (P =
      0.000, P = 0.001, respectively). In hospital A1, the report rate, sputum positive
      rate of reported cases, and sputum check rate of reported cases were not
      significantly different before and after intervention (P = 0.182, P = 0.116, and
      P = 0.583, respectively). In hospital B1, the report rate were significantly
      different before and after intervention (P = 0.004), while the sputum positive
      rate of reported cases and sputum check rate of reported cases were not
      significantly different (P = 0.909, P = 0.052, respectively). In hospital C1, the
      report rate was significantly higher after intervention (P = 0.025). In hospital
      C2, the sputum check rate significantly increased (P = 0.000). CONCLUSIONS:
      Intervention influences the hospitals abilities to detect pulmonary tuberculosis
      cases. However, more optimized and long-term intervention mechanism should be
      established to increase case detection rate of pulmonary tuberculosis.

PMID- 19771730
TI  - [Detection of specific interferon-gamma-secreting T cell response to
      Mycobacterium tuberculosis RD1-encoded antigens in pleural effusions, ascites,
      and cerebrospinal fluid].
AB  - OBJECTIVE: To detect Mycobacterium tuberculosis RD1-encoded antigens-specific,
      interferon-gamma (INF-gamma)-secreting T cells in pleural effusions, ascites, and
      cerebrospinal fluid. METHOD: The early secretory antigenic target-6 (ESAT-6) and
      culture filtrate protein-10 (CFP-10) peptides-specific T cells in peripheral
      blood mononuclear cell (MC), ascites MC, pleural effusions MC, and cerebrospinal
      fluid MC were detected using enzyme-linked immunospot assay (ELISPOT) for INF
      gamma. RESULTS: ESAT-6 or CFP-10 peptides-specific, INF-gamma-secreting T cells
      were detected in peripheral blood, ascites, pleural effusions, and cerebrospinal
      fluid, which marked the presence of tuberculosis infection. Patients with
      positive ELISPOT results of INF-gamma-release assay were all diagnosed as active
      tuberculosis. Spot forming cells in ascites and pleural effusions were much
      higher than those in peripheral blood (up to 6.4 and 31.9 times). CONCLUSION:
      Detection of RD1-encoded antigens-specific, INF-gamma-secreting T cells in
      pleural effusions, ascites, and cerebrospinal fluid provides a new way to
      diagnose tuberculosis infection.

PMID- 19771731
TI  - [Role of enzyme-linked immunospot assay and tuberculin skin test in the auxiliary
      diagnosis of initial pulmonary tuberculosis].
AB  - OBJECTIVE: To compare enzyme-linked immunospot assay (ELISPOT) and tuberculin
      skin test (TST) and explore their roles in the auxiliary diagnosis of initial
      pulmonary tuberculosis. METHODS: Totally 123 patients with initial pulmonary
      tuberculosis (tuberculosis group) and 102 patients with non-tuberculosis
      pulmonary disease (control group) were enrolled. The peripheral blood mononuclear
      cells of all participants were co-cultured with early secretiny antigen target
      6/culture filtrate protein-10 fusion protein (ESAT-6/CFP-10), and spot forming
      cells (SFCs) were enumerated by ELISPOT (ESAT-6/CFP-10-ELISPOT). TST was also
      performed simultaneously. RESULTS: ESAT-6/CFP-10-ELISPOT showed significantly
      higher numbers of SFCs after stimulation in tuberculosis group than in control
      group (P = 0.000). The sensitivity, specificity, positive likelihood ratio,
      negative likelihood ratio, positive predictive value, and negative predictive
      value of ESAT-6/CFP-10-ELISPOT were 91.1% (111/123), 81.4% (82/102), 4.60, 0.12,
      0.85, and 0.87 respectively, while the above values of TST were 65.6% (59/90),
      45.1% (46/102), 1.31, 0.76, 0.51, and 0.60, respectively. The sensitivity and
      specificity of ESAT-6/CFP-10-ELISPOT were significantly higher than those of TST
      (all P = 0.000). The number of SFCs were not significantly different between
      smear-positive tuberculosis subgroup and smear-negative tuberculosis subgroup (P
      = 0.166). The sensitivities were 91.8% (67/73) and 88.0% (44/50) in these two
      subgroups, respectively, (P = 0.448). CONCLUSIONS: ESAT-6/CFP-10-ELISPOT may be a
      more accurate approach for the auxiliary diagnosis of initial pulmonary
      tuberculosis; meanwhile, it offers certain diagnostic evidences for smear
      negative tuberculosis. However, its specificity may be affected by latent
      tuberculosis infection. On the contrary, TST has poor value in the auxiliary
      diagnosis of initial pulmonary tuberculosis.

PMID- 19771732
TI  - [Sensitivity of interferon-gamma release assay T-SPOT. TB in diagnosing
      extrapulmonary tuberculosis].
AB  - OBJECTIVE: To evaluate the sensitivity of an interferon-gamma release assay T
      SPOT. TB in the diagnosis of bacteriologically or histologically confirmed
      extrapulmonary tuberculosis. METHOD: Totally 31 patients with bacteriologically
      or histologically confirmed extrapulmonary tuberculosis in Peking Union Medical
      College Hospital received T-SPOT. TB assay to detect early secreting antigen
      target 6 or culture filtrate protein 10 peptides-specific T cells in the
      peripheral blood mononuclear cells (PBMCs). RESULTS: T-SPOT. TB assay showed
      positive results in 29 patients with extrapulmonary tuberculosis and the
      sensitivity was 93.5% (95% CI 84.8% - 100%). The median of spot forming cells
      (SFCs) in response to early secreting antigen target 6 peptides was 196/10(6)
      PBMCs (interquartile range, 72-532/10(6) PBMCs), the median of SFCs in response
      to culture filtrate protein 10 peptides was 276 SFCs/10(6) PBMCs (interquartile
      range, 72-568/10(6) PBMCs), and the median of the incorporate SFCs was 612/10(6)
      PBMCs (interquartile range, 192-1 152/10(6) PBMCs). CONCLUSION: T-SPOT. TB is
      highly sensitive in diagnosing extrapulmonary tuberculosis.

PMID- 19771733
TI  - [Combined application of enzyme-linked immunospot assay, positron emission
      tomography, and gene chip assay in the diagnosis of a case of chronic
      disseminated tuberculosis].
AB  - OBJECTIVE: To highlight the clinical features and diagnosis of chronic
      disseminated tuberculosis, with emphasizing the usefulness of several recently
      available diagnostic technologies in this setting. METHOD: We presented a case of
      chronic disseminated tuberculosis diagnosed with the combined application of
      interferon-gamma release assay T-SPOT. TB, 18F-fluorodeoxyglucose (FDG)-positron
      emission tomography (PET), and gene chip assay. RESULTS: A 53-year-old gentleman
      who had chronic cough for 7 years and fever for 2 weeks was referred to our
      hospital for further evaluation. 18F-FDG-PET/CT scan showed increased FDG uptake
      in multiple lesions involving bilateral lungs, supraclavicular, mediastinal and
      intro-abdominal lymph nodes and bones, mimicking metastatic malignancy. T-SPOT.
      TB assay revealed significant responses [ early secreting antigen target 6 (ESAT
      6): 3 908 spot forming cells (SFCs)/10(6) peripheral blood mononuclear cells
      (PBMCs), culture filtrate protein (CFP-10): 3 400 SFCs/10(6) PBMCs]. Subsequent
      biopsy of supraclavicular lymph node, lung, and ilium revealed granulomas, while
      culture of the obtained tissue yeilded mycobacteria. Gene chip testing identified
      M. tuberculosis sensitive to isoniazid and rifampin. After 10 weeks of treatment
      for tuberculosis, the patient's condition was improved and a second T-SPOT. TB
      assay showed significantly reduced responses (ESAT-6: 1528 SFCs/10(6) PBMCs; CFP
      10: 1460 SFCs/10(6) PBMCs). CONCLUSIONS: Timely diagnosis of chronic disseminated
      tuberculosis requires high index of suspicion. T-SPOT. TB assay, PET/CT, and gene
      chip assay may provide valuable information that facilitates further diagnostic
      procedures and treatment decision.

PMID- 19771734
TI  - [Repair of radius bone defect with the nano-hydroxyapatite/collagen/calcium
      alginate].
AB  - OBJECTIVE: To explore the osteogenic potential of the nano
      hydroxyapatite/collagen/calcium alginate composite implanted in animals. METHODS:
      Eighteen 3-month-old New Zealand white rabbits were adopted to prepare 15 mm
      segmental defect model at the middle part of radius. Rabbit models were randomly
      divided into experimental group and blank control group. Nano
      hydroxyapatite/collagen/calcium alginate was implanted into the defects of
      experimental group. Four, 8, and 12 weeks after operation, all specimens were
      examined by X-ray and histological methods. RESULTS: All the 18 rabbit models
      entered the final analysis. X-ray showed that osteotylus was seen in the whole
      defect area in the experimental group 12 weeks after operation, during which
      osteogenesis was more obvious than in weeks 4 and 8 and the bridge grafting of
      defect area was obviously visible. In the blank control group, osteotylus was
      only observed at the two ends of the defects, and no osteogenesis was found in
      the central part of the defect area. Histological examination showed that new
      osteoid formation was seen in internal porous zone in the experimental group in
      weeks 4 and 8; in week 12, more woven bone-like tissues were visible and
      trabecular-like structure was formed. CONCLUSION: The nano-hydroxyapatite/
      collagen/calcium alginate has good osteogenic potential.

PMID- 19771735
TI  - [Finite element analysis on stress change of the lumbar disc degeneration].
AB  - OBJECTIVE: To investigate the mechanical changes of the degenerated lumbar disc
      with finite element analysis. METHODS: A three dimensional finite element model
      of a human lumbar spine at the L3-L4 disc was established by the software MIMICS
      and ABAQUS based on computer tomography images. Degeneration was modeled by
      changes in geometry and material properties. The model was loaded with 0.3 MPa in
      axial plane. The von Mises stress on the annulus fiber, nucleus pulposus,
      endplate and facet joints in healthy and degenerated discs was compared. RESULT:
      Compared with healthy discs, the von Mises stress of disc distributed in the side
      of annulus fiber, the stress of nucleus pulposus decreased remarkably, the stress
      of endplate distributed in the posterior part, and the stress of facet joints
      increased for the degenerated disc. CONCLUSION: The finite element models can
      provide a method of understanding the relationship between biomechanical
      performance of the disc due to disc degeneration.

PMID- 19771736
TI  - [Different types of feeder cells for maintenance of human embryonic stem cells].
AB  - OBJECTIVE: To compare the effects of different types of feeder cells on
      supporting undifferentiation and high proliferation of human embryonic stem cells
      (hESC). METHODS: hESC were seeded on mouse embryonic fibroblasts (MEF), human
      marrow stromal cells (hMSC), and human foreskin fibroblasts (hFF), respectively.
      Colony number, cell quantity after digestion, and survival rate were observed by
      alkaline phosphatase (AP) staining and Trypan blue, and the biological properties
      of hESC after 5 passages were observed by immunofluorescence staining. RESULTS:
      Although all the three feeder layers could support the formation of hESC colonies
      and maintain pluripotency, the morphology of colonies on different feeder layers
      remarkably varied. The stage-specific embryonic antigen-3 and AP staining were
      positive on three types of feeders. The number of colonies, number of cells
      produced, and cell survival rates were significantly higher on MEF than on human
      feeder cells (P < 0.01). Furthermore, the number of AP-positive colonies and cell
      quantity were also significantly higher on hMSC than on hFF (P < 0.01).
      CONCLUSIONS: All three types of feeder cells are able to support the growth of
      hMSC, although MEF are more favourable for the proliferation. Two types of human
      feeder cells lay the foundation for the removal of animal-derived hESC culture
      system. hMSC is superior to hFF in supporting the proliferation of hESC.

PMID- 19771737
TI  - [Morphology of nitric oxide synthase positive neurons in the cerebellar cortex of
      midanaphase human fetus].
AB  - OBJECTIVE: To investigate the growth and development of nitric oxide synthase
      (NOS)-positive neurons in the cerebellum of human fetus in the midanaphase.
      METHOD: The positive expression of the NOS-positive neurons in the cerebellum of
      midanaphase human fetus was observed by immunohistochemistry. RESULTS: By the
      sixth to seventh month of gestation, NOS-positive neurons were seen in the
      ependymal layer of the cerebellum. The nucleus was oval-shaped and the neurons
      had short and small processes. By the eighth to ninth month, NOS-positive neurons
      were found in the central layer of the cerebellum and the nucleus was round-,
      oval-, or fusiform-shaped; meanwhile, the neurons grew larger in size with richer
      cytoplast and heavier staining. The beaded nerve fibers reached the marginal
      layer and the layer became thickened on the tenth month, which generally was
      composed of 5 to 6 layers of NOS-positive neurons that were tightly aligned. Some
      NOS-positive neurons were in smaller size with the cell body and the nerve fibers
      grew well. CONCLUSION: Nitric oxide generated by NOS of the NOS-positive neurons
      in the cerebellum plays an important role in the differentiation, proliferation,
      and migration of neurons and gliacytes.

PMID- 19771738
TI  - [Organic anion transporter system mediates the transport of aristolochic acid in
      tubular epithelial cells].
AB  - OBJECTIVE: To investigate whether aristolochic acid can be transported into human
      kidney proximal tubular cell (HKC) and its potential mechanism. METHODS:
      Intracellular aristolochic acid was measured by liquid chromatography-tandem mass
      spectrometry. The release of lactate dehydrogenase (LDH) induced by aristolochic
      acid in the presence of organic anion transporter inhibitor (probenecid) or
      organic cation transporter inhibitor (tetraethylammonium) was evaluated. The
      effects of probenecid on aristolochic acid induced connective tissue growth
      factor (CTGF) mRNA and protein expression were also examined by real time
      polymerase chain reaction and Western blot, respectively. RESULTS: Aristolochic
      acid was detected in the suspension of the denatured HKC after incubation with
      aristolochic acid sodium salt. The release of LDH from HKC, which was induced by
      60 mg/L aristolochic acid sodium salt, was significantly inhibited by 1 mmol/L
      probenecid (P < 0.01), but not by 1 mmol/L tetraethylammonium. The increased CTGF
      mRNA and protein expression in HKC stimulated by 40 mg/L aristolochic acid sodium
      salt was significantly down-regulated by 1 mmol/L probenecid (P < 0.05), with an
      inhibition rate of 16% and 21%, respectively. CONCLUSION: Aristolochic acid can
      be transported into HKC by organic anion transport system, and then exerts its
      biological effects.

PMID- 19771739
TI  - [Effect of Lewis y antigen on regulating gene expression of partial drug
      resistance associated proteins in human ovarian cancer cell line RMG-I-H].
AB  - OBJECTIVE: To investigate the influence of Lewis y antigen on the gene expression
      of partial drug resistance associated proteins in human ovarian cancer cell line
      RMG-I-H. METHODS: RT-PCR was used to determine the gene expressions of partial
      drug resistance associated proteins in RMG-I-H cell line transfected with alpha1,
      2-fucosyltransferases gene and RMG-I cell line, as well as in RMG-I-H treated
      with or without anti-Lewis y monoclonal antibody at the concentration of 10
      micro/g/ml. The immunocytochemical method was used to detect the expression of P
      glycoprotein (P-gp) in RMG-I and RMG-I-H cell lines. RMG-I and RMG-I-H cells were
      transplanted into nude mice and the expression of P-gp in the tissues was
      measured by immunohistochemistry. RESULTS: The mRNA expressions of protein kinase
      C-alpha (PKC-alpha), topoismerase I ( Topo I ), multidrug resistance-associated
      protein-1 (MRP-1), and MRP-2 were significantly higher in RMG-I-H cells than
      those in RMG-I cells (0.46 +/- 0.02 vs. 0.27 +/- 0.05, 0.82 +/- 0.08 vs. 0.52 +/-
      0.04, 0.66 +/- 0.07 vs. 0.34 +/- 0.12, and 0.44 +/- 0.08 vs. 0.23 +/- 0.05; all P
      < 0.05). However, the mRNA expression of multi-drug resistance 1 (MDR-1) was
      significantly lower in RMG-I-H cells than that in RMG-I cells (0.26 +/- 0.05 vs.
      0.45 +/- 0.08, P < 0.05). The P-gp level increased in RMG-I-H cells compared with
      that in RMG-I cells both in vivo and in vitro (P < 0.05). Expressions of MDR-1,
      MRP-1, MRP-2, PKC-alpha, and Topo I mRNA decreased by the time in RMG-I-H cells
      treated with anti-Lewis y monoclonal antibody (all P < 0.05), while mRNA
      expressions of those genes in the control group did not statistically change (P >
      0.05). In addition, MDR-1, MRP-1, MRP-2, PKC-alpha, and Topo I mRNA expressions
      were significantly lower in RMG-I-H cells treated with anti-Lewis y monoclonal
      antibody than those in the control group at 6 hours (all P < 0.05) and the
      inhibition ratios were 48.55%, 77.50%, 70.18%, 45.86%, and 46.13%, respectively.
      CONCLUSION: The Lewis y antigen of the human ovarian cancer cell surface is
      closely correlated with the regulation on the gene expression of partial drug
      resistance associated proteins.

PMID- 19771740
TI  - [Diagnostic specificity of dynamic assessment and monitoring of spirometry in
      asthma].
AB  - OBJECTIVE: To evaluate the diagnostic specificity of dynamic assessment and
      monitoring using a portable spirometer in diagnosis and differential diagnosis of
      asthma. METHODS: We retrospectively reviewed the results of dynamic monitoring of
      spirometry in 145 symptomatic patients with physician-diagnosed asthma. Flow
      volume curve and simultaneous symptoms and mood were measured in a fixed-time
      thrice-daily assessment schedule for 2 weeks. Patients were allowed to make
      additional measurements in case of symptom exacerbations. RESULTS: The clinical
      data of 51 males and 94 females with a mean age of (39.1 +/- 13.0) years (ranged
      from 10 to 65 years) were analyzed. Duration of asthma before study was (6.7 +/-
      9.9) years. Of 145 patients with physician-diagnosed asthma, 126 (87%) could be
      conclusively confirmed for a diagnosis of asthma. Asthma was misdiagnosed in 14
      patients (9.7%). Overdiagnosis of asthma was observed in 5 patients (3.4%).
      CONCLUSION: Dynamic assessment and monitoring using a portable spirometer by
      revealing variability and reversibility of airway obstruction may provide an
      additional tool for diagnosis and differential diagnosis of asthma.

PMID- 19771741
TI  - [Changes of insulin resistance and islet beta cells function in subjects with
      high-normal blood pressure].
AB  - OBJECTIVE: To investigate the changes of insulin resistance and islet beta cells
      function in subjects with euglycemia and high-normal blood pressure. METHODS:
      Total 423 subjects were divided into normal blood pressure group and high-normal
      blood pressure group. Body height, weight, waist and hip circumference, and
      biochemical data were measured. Homeostasis model assessment of insulin
      resistance (HOMA-IR), insulin sensitivity index (ISI)-composite, and first-phase
      (1 PH) Stumvoll index were calculated. Results Waist circumference, total
      cholesterol, triglyceride, low-density lipoprotein cholesterol, HOMA-IR were
      significantly higher and IPH Stumvoll index and ISI-composite were significantly
      lower in high-normal blood pressure group than in normal blood pressure group (P
      < 0.05). Systolic blood pressure (SBP) was positively correlated with HOMA-IR (r
      = 0.122) and negatively correlated with 1PH Stumvoll index (r = -0. 159) and ISI
      composite (r = -0.131) (P < 0.05). SBP and triglyceride were independent factors
      for IPH Stumvoll index. CONCLUSION: Insulin resistance and islet dysfunction may
      exist in subjects with high-normal blood pressure.

PMID- 19771742
TI  - [Diagnostic value of CT enterography in patients with Crohn's disease].
AB  - OBJECTIVE: To assess the diagnostic value of CT enterography in patients with
      Crohn's disease. METHODS: Multi-detector CT enterography and small bowel follow
      through were performed in 30 patients with Crohn's disease. The locations and
      characteristics of the intestinal and extra-intestinal lesions detected by both
      two techniques were compared. RESULTS: Skip lesions were diagnosed in 16 patients
      (53.3%) by CT enterography and in 9 patients (30%) by small bowel follow-through
      (P = 0.039). Mucosal changes were detected in 29 patients (96.7%) by CT
      enterography and in 18 patients (60%) by small bowel follow-through (P = 0.001).
      Among 11 patients whose small bowel follow-through did not show abnormal mucosal
      changes, 8 patients underwent endoscopy, which showed superficial ulcer with or
      without mucosal congestion and edema in 5 patients, mucosal congestion and edema
      in 2 patients, and mucosal erosion in 1 patient. CT enterography and small bowel
      follow-through consistently depicted fistula in 3 patients and had no significant
      difference in diagnosing intestinal stenosis. CT enterography also exclusively
      detected abdominal abscess in one patient. CONCLUSIONS: CT enterography is
      superior to small bowel follow-through in diagnosing the disease location and
      characteristics of Crohn's disease; furthermore, it can detect more extra
      intestinal lesions. CT enterography has potential to replace small bowel follow
      through as the imaging examination of choice for patients with Crohn's disease.

PMID- 19771743
TI  - [Advances in clinical applications of T-SPOT. TB for interferon-gamma release
      assay in the immunodiagnosis of tuberculosis].
AB  - T-SPOT. TB is an interferon-gamma release assay to detect T-cell response to
      early secreting antigen target 6 and culture filtrate protein 10 peptides by
      enzyme-linked immunospot assay for tuberculosis diagnosis. It is highly sensitive
      and specific, and will not be affected by the subject's immune status and
      Bacillus Calmette-Guerin vaccination. This assay has been licensed for in-vitro
      diagnosis in Europe and the United States. Its potential roles in distinguishing
      active tuberculosis from latent tuberculosis infection and predicting active
      tuberculosis among individuals with latent tuberculosis have been increasingly
      studies. This article reviews the advances in the clinical application of T-SPOT.
      TB.

PMID- 19771744
TI  - [Potential value of Mycobacterium tuberculosis RD1 region-encoded proteins in the
      diagnosis of tuberculosis].
AB  - Nine proteins encoded by Mycobacterium tuberculosis RD1 region are important
      protective antigens that become absent in long passaging of Mycobacterium
      tuberculosis. They only exist in pathogenic Mycobacteria and are absent in
      Bacille Calmette-Guerin and environmental Mycobacteria. With good
      immunogenicities, they may play an important role in the diagnosis and prevention
      of Mycobacterium tuberculosis. This article reviews recent studies on using RD1
      encoded proteins as antigens in the diagnosis of active tuberculosis and
      tuberculous pleurisy.

PMID- 19771745
TI  - [The I-PRESERVE study].

PMID- 19771746
TI  - [Evaluation of ventricular function in the fetus].
AB  - Congenital heart disease is the most frequent neonatal malformation, with an
      estimated prevalence between 0.8% and 1%. Echocardiography is an important tool
      for diagnosis and follow-up in cardiology, because it is easy to use,
      inexpensive, and noninvasive. The study of fetal heart by means of
      echocardiography allows early diagnosis and treatment of fetal heart anomalies
      and dysfunction, and such a technique is increasingly used. This exam is often
      required after morphological fetal echography, when a congenital heart disease is
      suspected or when there is an increased risk of congenital heart disease. Fetal
      echocardiography allows to evaluate the cardiac anatomy and function or cardiac
      rhythm. The purpose of this review is to summarize the main parameters and
      echocardiographic techniques for the assessment of heart rhythm and function: two
      dimensional echocardiography, Doppler, tissue Doppler, and two-dimensional
      strain.

PMID- 19771747
TI  - [Clinical practice: Ebstein's anomaly].
AB  - Ebstein's anomaly is a rare malformation of the tricuspid valve that has
      anatomopathologic and clinical implications, accounting for < 1% of all cardiac
      malformations. Usually, the tricuspid valve has three leaflets and, if Ebstein's
      anomaly occurs, such leaflets are malformed: one-two leaflets are stuck to the
      wall of the heart so that they cannot move normally, furthermore other
      abnormalities can also coexist. Therefore, the awareness of the different
      anatomical, hemodynamic and clinical variables of Ebstein's anomaly is crucial to
      treat properly, surgically or not, such malformation. The present paper takes
      into account current natural history, diagnostic criteria and classification,
      echocardiographic features, and prognosis useful to the accurate recognition and
      management options of Ebstein's anomaly.

PMID- 19771748
TI  - [Real-time three-dimensional echocardiography: current applications, advantages
      and limits for the evaluation of the left ventricle].
AB  - In the last decades the introduction and development of echocardiography allowed
      a significant improvement in the diagnosis as well as in the morphological and
      functional evaluation of several heart diseases, and today many therapeutic
      decisions are taken based on the results of the echocardiographic examination.
      One of the most important development in the field of echocardiography is three
      dimensional imaging, which has evolved from the slow and labor-intense off-line
      reconstruction techniques to the faster and simpler real-time volumetric imaging,
      which has the potential to be integrated in routine clinical practice. One of the
      major proven advantages of real-time three-dimensional echocardiography is the
      evaluation of left ventricular volume, mass and function, which is achieved by
      eliminating the need for geometric modeling and the errors caused by
      foreshortened views. In this review we discuss the state-of-the-art and
      anticipate future developments of real-time three-dimensional echocardiography
      that are relevant to its application to the left ventricle.

PMID- 19771749
TI  - [Echocardiographic evaluation of the athlete's heart: from morphological
      adaptations to myocardial function].
AB  - The definition of the athlete's heart includes the mechanisms of cardiac
      adaptation to training, characterized by the increase of internal chamber
      dimensions, ventricular wall thickness, and atrial chambers. The morphology of
      the athlete's heart is intermediate between concentric and eccentric left
      ventricular hypertrophy (LVH), in relation to the large prevalence of mixed
      sports activities and training protocols (including both aerobic and anaerobic
      exercise). Echocardiography is the tool of choice for the assessment of the
      athlete's heart and also for the differentiation of physiologic and pathologic
      LVH (hypertrophic cardiomyopathy and LVH due to arterial hypertension). The
      initial echocardiographic approach includes the quantitative analysis of the left
      ventricle, in order to calculate left ventricular mass, left ventricular mass
      index and relative wall thickness for diagnosing concentric or eccentric LVH.
      Tissue Doppler (pulsed or color modality) and strain rate imaging (Doppler or two
      dimensional modality) may give additional information to the standard indices of
      systolic function. Diastolic function can be evaluated not only by standard
      Doppler transmitral inflow measurements but also using pulsed tissue Doppler,
      which may allow to distinguish the athlete's LVH from diastolic impairment of
      hypertensive patients or hypertrophic cardiomyopathy by the simple determination
      of myocardial early diastolic velocity. Also the morphological and functional
      features of the left atrium and of the right ventricle can be assessed in the
      athlete's heart by combining standard echocardiography with new echocardiographic
      technologies.

PMID- 19771750
TI  - [B-type natriuretic peptide and Doppler echocardiography in the diagnosis of
      heart failure: alternative or complementary tools?].
AB  - Several studies have demonstrated the usefulness of B-type natriuretic peptide
      (BNP) dosage in patients referring for acute dyspnea in the emergency department.
      BNP is strongly associated not only with the evidence but even with the degree of
      heart failure, and BNP values are particularly increased in the advanced NYHA
      classes and in patients with poor prognosis. High BNP levels correlate with
      echocardiographic indexes of left ventricular and right ventricular systolic
      dysfunction but even better with diastolic dysfunction and degree of left
      ventricular filling pressure. However, in presence of some clinical confounders,
      such as obesity, renal insufficiency and anemia, BNP dosage itself cannot be
      interpretable. Under these circumstances, Doppler echocardiography is able to
      identify with better accuracy patients affected by heart failure. Algorithms
      built taking into account clinical and echocardiographic parameters as well as
      BNP measurements are already available in the guidelines of the European Society
      of Cardiology on heart failure with normal ejection fraction. They will lead to a
      better and earlier identification, better risk stratification and management of
      patients referring for heart failure.

PMID- 19771751
TI  - [Low T3 syndrome and left ventricular diastolic function].
AB  - BACKGROUND: Recent data suggest that low triiodothyronine (T3) syndrome may
      contribute to the pathophysiology of cardiac diseases. Because the development of
      diastolic dysfunction occurs early in a failing heart, we evaluated whether
      patients with low T3 syndrome show abnormalities in diastolic function, also in
      absence of overt cardiovascular disease. METHODS: Thirty-four patients with low
      T3 syndrome and 34 controls with normal levels of free T3 (FT3) underwent a
      complete Doppler echocardiographic examination. Criteria of exclusion from the
      study were the presence of cardiovascular disease or traditional cardiovascular
      risk factors, a primitive thyroid disease, cachexia, and the use of drugs
      affecting the thyroid function. RESULTS: Patients with low T3 syndrome, if
      compared with controls, show evidence of left ventricular diastolic dysfunction,
      documented by prolongation of the isovolumic relaxation time (120 vs 75 ms, p <
      0.0001) and a reduction in the early diastolic mitral flow velocity/late
      diastolic mitral flow velocity ratio (0.66 vs 2.05, p < 0.0001), mainly due to
      the increased A-wave (0.96 vs 0.40 m/s, p < 0.0001). These alterations increase
      proportionally with FT3 reduction. CONCLUSIONS: Patients with low T3 syndrome
      show evidence of impaired left ventricular relaxation. Doppler echocardiography
      may be a useful non-invasive technique for the assessment of diastolic
      performance in these patients.

PMID- 19771752
TI  - [A case of quadricuspid aortic valve].

PMID- 19771753
TI  - HPV vaccination in Italy.

PMID- 19771754
TI  - Health care-acquired aspergillosis and air conditioning systems.

PMID- 19771755
TI  - Ehrlichioses and anaplasmoses: (re)emerging tickborne zoonoses in humans and in
      animals.

PMID- 19771756
TI  - Assessment of knowledge, attitude and practice of hand washing among health care
      workers in Ain Shams University hospitals in Cairo.
AB  - Most nosocomial infections are thought to be transmitted by the hands of health
      care workers. The aim of this work was to assess the knowledge, attitude and
      practice of hand washing among health care workers (HCW) in Ain-Shams University
      hospitals and to investigate the presence of the necessary facilities and
      supplies required for hand washing (HW) in ten wards. A cross-sectional
      descriptive and observational study was conducted for six months from June till
      November 2006. Observation of the HCW for hand washing practice was done at any
      opportunity of contact with the patients in the different wards by members of the
      infection control team. Knowledge & attitude of HCW towards hand hygiene was done
      through self-administered questionnaire to HCW in 10 different departments. The
      total opportunities observed were 2189 opportunities. Doctors showed a
      significantly higher compliance (37.5%) than other groups of HCW (P = 0.000),
      however only 11.6% of the opportunities observed for doctors were done
      appropriately. The most common type of HW practiced among HCW was the routine HW
      (64.2%) and the least was the antiseptic HW (3.9%). Having a short contact time
      and improper drying (23.2%) were the most common errors that lead to
      inappropriate HW. Most of the wards had available sinks (80%) but none of them
      had available paper towels. The mean knowledge score was higher in nurses
      compared to doctors (42.6 +/- 1.7 versus 39.1 +/- 10.5). Most of the nurses
      (97.3%) believe that administrative orders and continuous observation can improve
      hand washing practices. Implementation of multifaceted interventional behavioral
      hand hygiene program with continuous monitoring and performance feedback,
      increasing the supplies necessary for HW and institutional support are important
      for improving the compliance of hand hygiene guidelines.

PMID- 19771757
TI  - Prevalence of occupational voice disorders in teachers.
AB  - INTRODUCTION: In Italy the number of teachers among private and public schools is
      around one million. Voice disorders are thought to be one of the major
      occupational hazards of school teaching; in fact the teachers often use their
      voice with high-intensity, in noisy classes, for a long time and without suitable
      breaks. The aim of the study was to assess the prevalence of voice problems in
      teachers of Naples district, identifying risk factors for developing voice
      pathology. METHODS: In this study we evaluated 504 teachers (322 F-182 M) with an
      age ranging between 24 and 62 years, randomly choiced in 28 schools of the
      district of Naples submitted to a questionnaire to determine the prevalence of
      voice disorders. In our study we have also introduced a comparison group of not
      teachers workers of 402 subjects (244 F-158 M); they were in the same age range
      as the teacher sample (range: 22-65 years). The control group was also submitted
      to a questionnaire regarding sociodemographic characteristics, smoking and
      alcohol use, a self-report of voice problems, voice symptoms, frequency of acute
      and chronic voice problems, absenteeism due to voice problems. RESULTS: The
      prevalence of reporting a current voice problem was significantly greater in
      teachers compared with not-teachers (8.7% vs 2.9%), as the prevalence of voice
      disorders during their lifetime too (51.4% vs 25.9%), chi2 = 86.672, p < 0.001.
      Women, compared with men had a higher lifetime prevalence of voice disorders. An
      other important data evidenced, is that 116 workers of the teachers group
      (23.01%) have been forced, during their professional activity, to miss job for
      problems related to voice; only 22 subjects of control group (5.47%) instead,
      missed job for voice troubles. DISCUSSION AND CONCLUSIONS: This study confirms
      that teachers have a higher rate of self-reported voice problems than subjects
      working in other occupations. Teachers, compared with not-teachers, were
      significantly more likely to have experienced multiple voice symptoms including
      hoarseness, discomfort while using their voice, difficulty projecting their voice
      and tiring or change in voice quality after short use. Large proportion of these
      problems may be preventable and prevention programs need to be developed and
      evaluated. Italian teachers do not receive any preventive voice training; that,
      in combination with poor hygienic work conditions, could increase health
      problems. Thus, voice training of teachers and teacher college students in some
      cases should be considered as a useful tool to prevent voice disorders.

PMID- 19771758
TI  - Evaluation of microbial contamination of air in two haematology departments
      equipped with ventilation systems with different filtration devices.
AB  - BACKGROUND: Nosocomial infections (NI) are above all due to health-care workers
      practices, but also the contamination of the environment could lead to their rise
      in health-care facilities. Introduction. In the last years, the incidence of NI
      has increased due to a substantial rise in the number of immuno-compromised
      patients. These patients are often gathered in hospital areas declared at "high
      risk" of infection such as Hematology and Bone Marrow Transplant ward. In this
      study, we evaluated microbial contamination of the air in two divisions with high
      risk patients, focusing on the validity of the air system with correlation to the
      presence or not of the HEPA absolute filters. METHODS: An environmental
      surveillance study has been carried out in two Divisions of Haematology, in two
      different Hospitals. Investigations have been performed by sampling air and by
      analyzing bacterial and fungal growth on microbiology plates after an incubation
      period. RESULTS: Unit A, without HEPA filters in the ventilation systems, showed
      a gradual increase in the bacterial load 20 and 60 days after cleaning of the
      ventilation system. Mycetes and Aspergilli were not present in basal conditions,
      at 20 or 60 days after decontamination. Unit B, equipped with HEPA filters placed
      at the inlet vents, showed extremely low values of the bacterial load either in
      basal conditions or upon inspection 60 days after cleaning. No mycetes were
      present. DISCUSSION: From the results obtained, it was evident that following the
      cleaning operation, the quality of the air is excellent in both types of
      equipment, since no mycetes were present and the bacterial load was < 20 CFU/mc
      in all the sites tested. However, although in subsequent controls mycetes were
      absent in both types of equipment, a great difference in the suspended bacterial
      load was found: Unit B was close to sterility whereas in Unit A a progressive
      increase was observed.

PMID- 19771759
TI  - Disability management: the application of preventive measures, health promotion
      and case management in Italy.
AB  - BACKGROUND: Disability Management can be defined as a practice to improve
      workers' health and to reduce the impact and costs of disability. The aim of the
      study was to estimate the diffusion of DM in Italian companies. METHODS: A survey
      was conducted using a questionnaire, the Worksite Disability Management Audit.
      The questionnaire was structured into five parts addressing the following
      domains: 1) characteristics of the company; 2) health promotion activities; 3)
      preventive measures; 4) case management; 5) disability management. We selected
      public and private companies and collected information by direct interview.
      RESULTS: Twenty companies entered the survey. Twelve Companies (60%) indicated
      that health promotion programs and sensibilisation campaigns are usually carried
      out. The presence of an individual who provided workplace safety indications and
      materials was stated by 19 companies (95%). Periodical medical examinations are
      carried out by 19 companies (95%); 16 (80%) have an evaluation process for
      ergonomics concerns. Risk assessment and analysis are performed by all companies
      and the security procedures and policies are updated at least once in a year in
      40% of cases. Health status monitoring of injured workers is performed in eight
      (40%) of the companies, while Disability Management is present as a whole in only
      three companies. CONCLUSIONS: This survey highlights that Disability Management
      is not undertaken in most companies and that, where applied, there is still
      confusion and disorganization about ways to promote health and manage workers'
      illness and disability. Hence, there is still the need to promote an all
      inclusive evaluation and management of workers' safety, illness and disabilities.

PMID- 19771761
TI  - Survey of domestic accidents in the elderly in the Province of Genoa (northern
      Italy).
AB  - INTRODUCTION: Accidents in the home are a major public health issue in most
      industrialised countries, as they are a frequent cause of injury and death.
      Moreover, since a considerable portion of such accidents involve elderly people,
      it is important to assess their social impact in this population. In Italy, the
      available data indicate that well over 3 million people per year suffer accidents
      in the home, and that this number is rising. The aim of the present study was to
      evaluate the number, characteristics and causes of domestic accidents among the
      elderly. MATERIALS AND METHODS: The study population was made up of subjects of
      both sexes aged between 65 and 92 years admitted to first aid units and emergency
      departments of hospitals in Genoa. The investigation was conducted by means of an
      ad hoc questionnaire designed to record the circumstances of the accident, the
      functional capacity of the subject involved, any risky behaviour enacted and the
      safety profile of the subject's home. RESULTS: The study enrolled 111 voluntary
      participants: 62 women and 49 men. At the time of the accident, subjects were
      engaged in the following activities: housework (36.9%) "rest" (14.5%), ablutions
      (10%), gardening (9%), leisure activities (8.1%), eating and drinking (2.7%). The
      most common injuries were bruises (39.6%), followed by fractures (23.4%) and cuts
      (23.4%); the frequency of other, some time more severe injures (burns, poisoning,
      asphyxia, crush injuries, etc.) was,fortunately, very low. Anyway, taking into
      account their consequences, their surveillance and prevention is very important.
      Most subjects were deemed to be in good health and, in 76% of cases, the safety
      profile of their houses proved to be satisfactory. DISCUSSION AND CONCLUSIONS:
      The data collected during this survey are in line with those yielded by national
      and international studies. They show that the elderly are very vulnerable to
      domestic accidents and that, even in the event of only slight injury, the
      management of elderly victims requires a strong organisational commitment on the
      part of relatives and considerable financial resources for healthcare services.
      Falling proved to be the main cause of injury. Clearly, efforts to reduce the
      cost of accidents in the home should aim to implement preventive intervention
      among elderly people, since the elderly population is destined to grow as a
      result of increasing life expectancy. In particular, preventive action should
      focus on reducing the incidence of falls by eliminating risk-related structural
      features in domestic settings as far as possible and by raising public awareness
      of the problem through health education campaigns.

PMID- 19771760
TI  - Low cadmium concentration in whole blood from residents of northern Sardinia
      (Italy) with special reference to smoking habits.
AB  - INTRODUCTION: The present study was initiated to investigate the cadmium
      concentrations in whole blood of Northern Sardinian, non-occupationally exposed
      adult subjects. Sardinia is a large Italian island which differs genetically and
      environmentally from other mainland Italian areas. METHODS: Two hundred and forty
      three adults (157 females and 86 males) were selected in the study area from
      subjects who were undergoing blood collection for laboratory analysis during the
      period January 2005-May 2005. Whole blood was analysed by graphite furnace atomic
      absorption spectrometer equipped with a Zeeman-effect background corrector
      (Perkin Elmer ZLS5100) and an auto sampler. The adopted analytical procedure uses
      the Stabilized Platform Temperature Furnace (STPF) technique. RESULTS: The mean
      value of Blood Cadmium Concentration (BCdC), expressed as Geometric Mean, was
      0.32 pg/l (CI 95%: 0.31-0.34 l) in non-smokers to 034 pg/l (CI 95%: 0.30-0.39
      pg/l) in ex-smokers up to 0.47 gg/ll(CI 95%: 0.42-0.53 pg/l) in smokers (p <
      0.0001). DISCUSSION: The results show that BCdC levels in Northern Sardinian non
      occupationally exposed adults are lower than levels found in many other regions,
      including those within Italy. Nevertheless, similar values have been detected in
      other European countries and cities. CONCLUSIONS: In relation to other reports in
      which data were analysed by strata for smoking habit and age, we found similar
      BCdC values among non smokers. However, Sardinian smokers seem to show lower
      levels of blood cadmium.

PMID- 19771762
TI  - Gender health and policies: the state of the art from exposure to solutions.
AB  - OBJECTIVE: To synthesize the determinants of gender inequalities through a
      narrative review that: (i) describes gender related variables that can create
      different levels of health; (ii) describes key points that may assist in policy
      development and its reorientation towards gender differences; (iii) debates
      potential approaches in understanding gender issues. METHODS: Review of the
      international literature through online databases (Pubmed), search engines,
      publications and documents from "grey literature". INCLUSION CRITERIA:
      publications from 1997, English language; keywords used: gender based analysis;
      gender and public policy; women's health; gender differences; health policy;
      gender impact assessment. Among the 300 papers retrieved, 55 were selected for
      relevance. RESULTS: We performed a narrative synthesis of the included
      literature, regarding: (i) gender differences and their determinants; (ii)
      elements for the changing; (iii) possible approaches; (iv) gender influences the
      pursuit of health and health care access through specific variables; (v) health
      policies can modify these variables only by a minimal percentage. These
      interventions should guarantee equity and allow efficient resources allocation.
      The gap between political announcements and real policy implementation remains
      unchanged. (vi) Standard approaches to the topic are not feasible due to the
      scarcity of a specific literature and the numerous cultural differences.
      CONCLUSIONS: . Gender analysis of policies suggests they can differently affect
      women in comparison to men. However, reforms, strategies and interventions
      introduced in the last two decades, have achieved a limited success towards
      better gender equality in health. The main aim is to attack the structural
      sources of gender inequity in the society.

PMID- 19771763
TI  - An ultrastructural study of the histogenesis of haemangioblastoma.
AB  - Seven cases of cerebellar haemangioblastoma, not associated with von Hippel
      Lindau disease (sporadic haemangioblastomas), were studied by light and electron
      transmission microscopy. Morphological features that might provide information
      about the histogenesis of the tumour were examined. The ultrastructural data
      indicate both the common ancestry of the different cytotypes that make up the
      tumour, and the mesenchymal origin of the elements present, which were also
      documented by their capacity to synthesise lipid droplets in the cytoplasm (a
      process of lipidization similar to that of pre-adipocytes).

PMID- 19771764
TI  - Cytology of the oral cavity: a re-evaluation.
AB  - Oral exfoliative cytology, while an economical and practical tool for diagnosis
      of squamous cell carcinoma and potentially malignant lesions, is not extensively
      used. The results of conventional (n = 89) and liquid-based (n = 411) oral
      diagnostic cytology cases are reported and compared to histological diagnosis.
      Cells were collected using either a Cytobrush device for conventional smears or a
      dermatological curette (AcuDispo) for liquid-based (Thin Prep) cytology. The
      "curette technique" allowed for the collection of "accidental" tissue fragments,
      utilized as microbiopsies. The sensitivity was 86.5% in conventional and 94.7% in
      liquid-based cytology; specificity was 94.3% and 98.9%, respectively; inadequate
      samples were present in 12.4% and 8.8% of cases, respectively. Although
      conventional cytology may be useful in oral squamous cell carcinoma and
      potentially malignant lesions, liquid-based cytology gives better results,
      enhances both the sensitivity and specificity, and also provides material for
      further investigations, e.g. DNA ploidy studies, microhistology, etc.

PMID- 19771765
TI  - Benign metastasizing leiomyoma: report of 2 cases and review of the literature.
AB  - Benign metastasizing leiomyoma (BML) is a benign spindle cell lesion affecting
      women who have undergone hysterectomy for uterine leiomyomas in young adulthood,
      and subsequently present pulmonary metastases during the peri-menopausal period.
      We present 2 cases of BML in women with prior medical history of hysterectomy for
      multiple myomas. Both patients presented pulmonary metastases at 17 and 12 years
      after hysterectomy. The pulmonary nodules were totally excised in the both cases,
      and neither patient experienced complications or recurrences after 1 and 2 years
      of follow up, respectively. BML is a rare benign entity with a debated
      pathogenesis. We have developed different hypotheses about its pathogenesis,
      mechanisms of spread, histological characteristics and commonly employed
      treatment modalities.

PMID- 19771766
TI  - Report of a case of intraosseous frontal meningioma.
AB  - Meningiomas without dural connection are rare lesions and often referred to as
      ectopic. Primary ectopic intraosseous meningiomas are uncommon, accounting for
      less than 2% of all meningiomas. Herein the authors describe a case of meningioma
      involving the frontal bone in a 43-year-old man and review the relevant
      literature.

PMID- 19771767
TI  - Undifferentiated gastric carcinoma with lymphoid stroma (lymphoepithelioma-like
      carcinoma/medullary carcinoma).
AB  - Undifferentiated gastric carcinoma with lymphoid stroma is a histological type of
      gastric cancer with favourable prognosis, microscopically characterised by nests
      of neoplastic epithelial cells intermingled with a dense lymphoid proliferation.
      Various studies have shown a close relationship between undifferentiated gastric
      carcinoma with lymphoid stroma and Epstein-Barr virus infection; the presence of
      viral DNA in tumour cell nuclei has been demonstrated using polymerase chain
      reaction and Epstein-Barr virus-encoded small RNA in neoplastic cell nuclei have
      been found using in situ hybridization. We describe two cases of undifferentiated
      gastric carcinoma with lymphoid stroma, one infiltrating the submucosa of the
      gastric body and the other invading the muscularis propria of the antrum. No
      lymph node neoplastic invasion was documented in either case. Epstein-Barr virus
      was detected in the neoplastic cell nuclei in both cases with in situ
      hybridization.

PMID- 19771768
TI  - Primary cutaneous marginal zone B-cell lymphoma: clinical and histological
      aspects.
AB  - According to the WHO-EORTC classification of cutaneous lymphomas, primary
      cutaneous marginal zone B-cell lymphoma are now well characterized. We report
      here a case of primary cutaneous marginal zone B-cell lymphoma in a 51 year-old
      man in which the diagnosis was made using both histology and immunopathology. The
      patient had no remarkable medical history, no history of either acute
      inflammation or insect bite, and presented with a 5 cm solitary asymptomatic
      erythematous firm, multinodular and infiltrated plaque on the back for 12 months.
      Histological examination and immunohistochemical study of a cutaneous biopsy
      provided a differential diagnosis between B cell lymphoma and lymphocytoma cutis.
      Full body work up revealed no signs of extracutaneous dissemination. The patient
      underwent surgical excision of the nodule. Histological examination showed a
      histological and immunophenotyping profile typical of primary cutaneous marginal
      zone B-cell lymphoma. The lesion was completely excised with clear margins and no
      recurrence occurred after a 12 month-follow-up period. Primary cutaneous marginal
      zone B-cell lymphoma are low-grade lymphomas that have an indolent course and a
      high tendency to recur. They should be differentiated from lymphocytoma cutis and
      from the other types of cutaneous B cell lymphomas that have a different course
      and prognosis.

PMID- 19771769
TI  - A product of wound-care research. Evidence-based assessments determine low
      prices, best quality.

PMID- 19771770
TI  - 2009 infection prevention & hospital cleaning survey. How clean is clean?

PMID- 19771771
TI  - Make logistics the focus of your supply chain plan.

PMID- 19771772
TI  - Warehouse system improves reliability.

PMID- 19771773
TI  - Understanding VRE is key to prevention.

PMID- 19771774
TI  - Infection prevention's involvement in pandemic preparedness strategies.

PMID- 19771775
TI  - [Bicycle accident. Would a helmet have prevented these injuries?].

PMID- 19771776
TI  - [Surveillance studies criticized. A marketing effort for expensive drugs? "Not
      throwing the baby out with the bath water" (interview by Dr. Beate Schumacher)].

PMID- 19771777
TI  - ["There are clear criteria for product surveillance studies"].

PMID- 19771778
TI  - [Impacts of fee reform show a mixed picture. Only some family practitioners can
      be satisfied].

PMID- 19771779
TI  - [Analysis by specialist groups and federal states. Silent winners, noisy losers-
      the crux of the fee reform].

PMID- 19771780
TI  - [New influenza. What you should know about vaccination (interview by Dr. Judith
      Neumaier)].

PMID- 19771781
TI  - [What is changing, what is becoming simpler--and where there are dangers. What
      will the new regulation for patient advance directives entail?].

PMID- 19771782
TI  - [Abuse is not excluded. The new regulation applies also without patient advance
      directives! (interview by Dr. med. Horst Gross)].

PMID- 19771783
TI  - [Borreliosis. Questionable diagnoses, questionable therapies].

PMID- 19771784
TI  - [Therapy of joint pain in arthrosis and arthritis. Classical nonsteroidal anti
      inflammatory agents, coxibs--or opioids?].

PMID- 19771785
TI  - [What do you read during the quieter summer season? Family medicine can be very
      fascinating].

PMID- 19771786
TI  - [Cancer pain: recommendations beyond the WHO-ladder].

PMID- 19771787
TI  - [Recurrent episodes of cystitis without detection of bacteria in young women].

PMID- 19771788
TI  - [Urinary catheter care in nursing homes: what has to be pointed out?].

PMID- 19771789
TI  - [Diarrhea after antibiotic therapy--what should be done?].

PMID- 19771790
TI  - [Diagnosis of coagulation disorders: first steps to be done].

PMID- 19771791
TI  - [Intermittent claudication induced by betablocker: what to do?].

PMID- 19771792
TI  - [Dyspepsia and heartburn in primary care: a rational and economic approach].

PMID- 19771793
TI  - [Severe acute bronchitis].

PMID- 19771794
TI  - [Biliary colic].

PMID- 19771795
TI  - [Genital dermatoses in older men].

PMID- 19771796
TI  - [Primary and secondary intussuception of the small intestine in adults. Two case
      reports].

PMID- 19771797
TI  - [Hypertension and sports: do we take the opportunity?].

PMID- 19771798
TI  - [Erectile dysfunction as a harbinger of cardiovascular events. Long-term vascular
      protection with telmisartan].

PMID- 19771799
TI  - [Concerning recognition of nursing research?].

PMID- 19771800
TI  - [New modalities of care in influenza A/H1N1].

PMID- 19771801
TI  - [New horizon in the forming of nursing].

PMID- 19771802
TI  - [Reform in the molding of nurses, a new dynamic].

PMID- 19771803
TI  - [New tools in the framing of nursing].

PMID- 19771804
TI  - [Involvement of nurses in the evaluation of their competence as students].

PMID- 19771805
TI  - [Questions and answers on nursing reform].

PMID- 19771806
TI  - [A nurse for twenty years, and still as passionate].

PMID- 19771807
TI  - [Rights and duties when faced with maltreatment].

PMID- 19771808
TI  - [A clown in a palliative care unit].

PMID- 19771809
TI  - [A game from the society of education of patients with heart failure].

PMID- 19771810
TI  - [Complexity of humanistic care within the concept of nursing].

PMID- 19771811
TI  - [Urgent heart care in urban settings, understanding the actions which might save
      lives].

PMID- 19771812
TI  - [How to act in the presence of a person with hemodynamic diseases].

PMID- 19771813
TI  - [Sister Mathilde Inchelin (1861-1940)].

PMID- 19771814
TI  - [Tenofovir, An antiviral agent with activity against HIV infections and hepatitis
      B].

PMID- 19771815
TI  - [Sensitizing the public to the importance of primary care].

PMID- 19771816
TI  - [The nurse specialist, an unknown reality].

PMID- 19771817
TI  - [Nurses, men like everyone else].

PMID- 19771818
TI  - [I have found that I have very traditional manners].

PMID- 19771819
TI  - [Different motives and biographies].

PMID- 19771820
TI  - [Moderate emotionality is chaos].

PMID- 19771822
TI  - [When collective suffering creates suffering].

PMID- 19771821
TI  - [Pathway to fulfilling individual nursing].

PMID- 19771823
TI  - [Care for HIV/AIDS during parturition].

PMID- 19771824
TI  - [First time in Africa: crisis and hope].

PMID- 19771825
TI  - [Multidisciplinary treatment and care].

PMID- 19771826
TI  - [When Andreas closed his dagger. (Part 1)].

PMID- 19771827
TI  - [The most important goal: health of nurses].

PMID- 19771828
TI  - [A question of identification].

PMID- 19771830
TI  - [Diary on an unforgettable experience].

PMID- 19771829
TI  - ["The informed nurse, promoter of human development"].

PMID- 19771831
TI  - [Home emergencies].

PMID- 19771832
TI  - [A response to essential needs].

PMID- 19771833
TI  - [Attending to sick children].

PMID- 19771834
TI  - [The doctor and the patient].

PMID- 19771835
TI  - [Study on physiological characteristics of seed germination of Ephedra sinica].
AB  - OBJECTIVE: To study the characteristics of the Ephedra sinica seed germination,
      to provide a basis for its cultivation. METHODS: The seed germination inhibitive
      substances were studied by water washing method; the seed vigor was determined by
      TTC method and red ink method, the influence of growth substances to seed
      germination was studied by agar medium cultivation, and the influence of
      different sand burying depth on seed germination was studied by sand medium
      cultivation. RESULTS: The seed germination rates of dry seeds, seeds as 12 h
      soaking with distilled water, 12 h washing by water and with ensheathe phyllary
      were 44%, 61%, 79.9% and 0%. Treated with 40 mg/L GA, the seed germination
      enhanced significantly as the maximum seed germination rate was 94% after 2 d.
      Treated with 40 mg/L IAA and 40 mg/L 6-BA, the seed germination delayed as the
      maximum seed germination rate appeared after 7 d, and the difference of seed
      germination index between treated and CK was significant (P<0.05). In the sand
      burying depth 0-6 cm, with the depth increasing, the seed germination rate
      gradually increased. But above 6 cm, when the depth increased, the seed
      germination rate gradually decreased. Moreover, as the sand burying depth
      increased, the root length changed in parabola-shaped and the stem length
      increased, but the root top radio decreased. CONCLUSIONS: The phyllary and seed
      of Ephedra sinica contain some seed germination inhibitors, adequate water
      washing, dealing with GA and so on can improve the seed germination rate and
      speed up the seed germination. Appropriate deep sand burying can also improve
      seed germination and seedling emergence of Ephedra sinica.

PMID- 19771836
TI  - [Study on propagation technology of Acanthopanax trifoliatus by cuttings].
AB  - OBJECTIVE: In order to obtain substantial clonal plants, we studied the cuttings
      propagation technology. METHODS: The cutting roots and stems of Acanthopanax
      trifoliatus were used as plant materials, and different materias, seasons and
      other conditions for cutting propagation were tested. RESULTS: It showed that the
      survival rate of stem segments was higher than that of root segments. The test of
      age of plant materials found that high survival rate could be obtained from semi
      lignified stem segments and the segments from the base stem could survive
      successfully. Autumn was more suitable for plants' survival. Moreover, the
      rooting rate reached 89.4% by inserting segments with leaves into sand soil after
      dipping into 1500 mg/L IBA for 10 s, and with plastic membrane and shading net
      covered. CONCLUSION: The rooting rate can increase significantly by collecting
      semi-lignified basal stems in autumn, cutting them for leaf cuttings, and
      inserting them into sand soil after dipping into 1500 mg/L IBA for 10 s.

PMID- 19771837
TI  - [Studies on X-ray diffraction Fourier fingerprint pattern of Cornu Elaphuri
      Davidiani].
AB  - OBJECTIVE: To establish the analytical method for the fingerprint pattern of
      Cornu Elaphuri Davidiani by X-ray diffraction. METHODS: Cornu Elaphuri Davidiani
      from different ages and different parts were analyzed and the fingerprint
      patterns were determined by X-ray diffraction. The degree of different
      fingerprint patterns was calculated and analyzed. RESULTS: The reference X-ray
      diffraction Fourier fingerprint pattern and characteristic diffraction peaks of
      Cornu Elaphuri Davidiani were obtained by fifteen samples of Cornu Elaphuri
      Davidiani from different ages and different parts. CONCLUSION: This method can be
      used for identification and evaluation of Cornu Elaphuri Davidiani.

PMID- 19771838
TI  - [Comparative studies on the amount of ginsenosides between the crown galls and
      Chinese medicinal materials of Panax quinquefolium].
AB  - OBJECTIVE: To provide theoretical basis for the production of ginsenosides by
      using modern biotechnologies, the comparative studies of the amount of
      ginsenosides between the crown galls and Chinese medicinal materials of Panax
      quinquefolium were carried out. METHODS: Total ginsenosides were determined by
      spectrophotometry, and the contents of ginsenoside Rb1, Rb3, Rc, Re were
      determined by HPLC. RESULTS: (1) The total ginsenosides in the crown galls of
      Panax quinquefolium (aftert 27 days' cultivation) was almost as much as that of
      Chinese medicinal material of Panax quinquefolium. (2) The contents of
      ginsenoside Rb1, Re in the crown galls were about half of that in Chinese
      medicinal materials of Panax quinquefolium, and ginsenoside Rc was about 80%. But
      the amount of ginsenoside Rb3 in the crown galls of Panax quinquefolium was much
      more than that in Chinese medicinal materials of Panax quinquefolium as almost 15
      times higher. CONCLUSION: The crown galls of Panax quinquefolium may be a new
      potential resource for large-scale production of ginsenosides.

PMID- 19771839
TI  - [Study on HPLC fingerprint of flavonoids from Houttuynia cordata by comparing
      with fingerprint reference].
AB  - OBJECTIVE: To establish a stable and repeatable HPLC fingerprint standard and
      evaluate the flavonoids from Houttuynia cordata qualitatively and quantitatively.
      METHODS: HPLC separation was performed on a C18 column with methanol-0.1%
      phosphoric acid mixed solution as mobile phase in gradient elution mode. The
      fingerprint reference was determined as one of the most typical chromatograms and
      used to be compared with other samples through Cosine and Relative Euclid
      Distance methods, thus the chromatographic fingerprints of flavonoids from
      Houttuynia cordata were evaluated by constitutes and contents, respectively.
      RESULTS: Fourteen mutual peaks were fixed in the HPLC fingerprint of flavonoids
      from Houttaynia cordata. It showed good results in validation tests in which the
      quercitrin's peak was set as the reference peak to calculate relative retention
      time and area of other peaks in the chromatograms, and the RSD were less than
      0.2% and 5.0%, respectively. The linear ranges for quercitrin was 1.07-83.4
      microg/mL (r=0.9999) and the average recovery was 100.3%. CONCLUSION: The method
      shows good repeatability, ruggedness and reliability. Comparing with the
      established reference fingerprint, the evaluation system including Cosine and
      Relative Euclid Distance methods lays dependable foundation for controlling the
      quality of Houttuynia cordata.

PMID- 19771840
TI  - [Studies on the chemical constituents of Xanthoceras sorbifolia].
AB  - OBJECTIVE: To study the chemical constituents of Xanthoceras sorbifolia for
      explaining the active compounds. METHODS: The constituents were isolated by
      silica gel column chromatography. Sephadex LH-20, MCI et al and the LC-MS-MS, 1H
      NMR, 13C-NMR, CD spectroscopic analysis were employed for the structure
      identification. RESULTS: 9 compounds were obtained and their structures were
      identified as (2R, 3R)-dihydromyricetin (I), myricetin (II), quercetin (III),
      (2R, 3S)-catechin (IV), gallocatechin (V), (2R, 3R)-3,3',5,5',7
      pentahydroxyflavanone (VI), (2S) -3',4',5,5',7-pentahydroxyflavanone (VII), (-)
      epigallocatechin (VIII) , proanthocyanidin A2 (IX). CONCLUSION: Compound I, IV,
      VI, VII are isolated from xanthoceras genus for the first time.

PMID- 19771841
TI  - [Studies on the chemical comstituents of Pithecellobium clypearia].
AB  - OBJECTIVE: To study the chemical constituents of Pithecellobium clypearia.
      METHODS: The compounds were isolated from Pithecellobium clypearia with column
      chromatography. Their structures were characterized on the basis of their
      physical and chemical preperties, as well as chromatographic and spectroscopic
      evidences. RESULTS: A pair of isomeric flavans consisting of 7, 3'-O-di
      gallyoltricetiflavan (I) and 7,4'-O-di-gallyoltricetiflavan (II), along with a
      catechin compound (-)-epigallocatechin-7-O-gallate (III) were isolated from the
      leaves and twigs of Pithecellobium clypearia. CONCLUSION: Compound I is a new
      flavan. Compound III is isolated from Pithecellobium genus for the first time,
      and its 13C-NMR data is firstly given in the present study.

PMID- 19771842
TI  - [Preparation and isolation on the rare ginsenoside derivatives with anti-cancer
      activity].
AB  - OBJECTIVE: To prepare and isolate the rare ginsenoside derivatives of anti-cancer
      activity. METHODS: Acid-degradation products of ginsenosides were isolated and
      purified by various chromatographic techniques such as silica gel and so on;
      compounds were identified and elucidated by spectral and chemical methods.
      RESULTS: Eleven compounds were obtained from the products of Acid-degradation.
      CONCLUSION: Compound I, II are discoverd from the roots, stems, leaves, fruits
      and alabastrums of Panax quinquefolium L. for the first time. Compound IX of
      derivate of the aglycone of protopanoxadiol ginsenoside was discovered and
      reported, having the conspicuous anti-cancer activity for the first time from the
      fruits of Panax ginseng.

PMID- 19771843
TI  - [Studies on the chemical constituents of the root and rhizoma of Ligusticum
      jeholense].
AB  - OBJECTIVE: To study the chemical constituents of the root and rhizoma of
      Ligusticum jeholense. METHODS: The constituents were isolated by silica gel
      column chromatography, Sephadex LH-20 column chromatography and their structures
      were elucidated through spectral analysis. RESULTS: Seven compounds were
      separated from the EtOH extracts. Their structures were identified as levistolide
      A (1), xiongterpene (2), linoleic acid (3), sucrose (4), daucosterol (5), ferulic
      acid (6) and beta-sitosterol (7). CONCLUSION: Compounds 1-5 are isolated from the
      genus for the first time.

PMID- 19771844
TI  - [Studies on the chemical constituents of Scyphiphora hydrophyllacea (II)].
AB  - OBJECTIVE: To study the chemical constituents of Scyphiphora hydrophyllacea.
      METHODS: The compounds were isolated and purified by repeated column
      chromatography on silica and Sephadex LH-20 gel and their structures were
      identified by spectral analysis. RESULTS: Six compounds were identified as
      friedelin (1), syringic acid (2), isoscopoletin (3), fraxetol (4), casuarinondiol
      (5) and guaiacylglycerol-beta-ferulic acid ether (6). CONCLUSION: All of these
      six compounds are isolated from Scyphiphora hydrophyllacea for the first time.

PMID- 19771845
TI  - [GC-MS analysis on the chemical constituents of essential oil from bark of
      Horsfieldia hainanensis].
AB  - OBJECTIVE: To analyze the constituents of the essential oil from the bark of
      Horsfieldia hainanensis. METHODS: The volatile oil was obtained by steam
      distillation. The chemical constituents were separated and identified by gas
      chromatography-mass spectrometry (GC-MS). The relative contents were determined
      by area normalization. RESULTS: The extraction rate of the bark of Horsfieldia
      hainanensis was 0.14%. 32 compounds were separated and identified, which
      accounted for 98.62% of the essential oil. The main chemical components of the
      essential oil were Copaene (25.55%), Naphthalene, 1,2,3,5,6,8a-hexahydro-4,7
      dimethyl-1-(1-methylethyl)-(11.14%), Hexanedioic acid, bis(2-ethylhexyl) ester
      (8.09%) , 9-Octadecenoic acid (7.04%), etc. CONCLUSION: It has provided
      scientific foundation for exploitation and utilization of Horsfieldia
      hainanensis.

PMID- 19771846
TI  - [Effects of Dan-Chuan-Hong decoction on myocardial apoptosis of acute myocardial
      ischemia in rats].
AB  - OBJECTIVE: To observe the effects of Dan-Chuan-Hong decoction on myocardial
      apoptosis of acute myocardial ischemia in rats. METHODS: Rats received Guan-Xin
      Er-Hao, Dan-Chuan-Hong or normal saline at 30 minutes before ischemia. The model
      of acute myocardial infarction (AMI) in rats was set up by ligating the
      descending branch of left coronary artery. 3 hours after AMI, the hearts were
      isolated to detect the apoptosis of myocardial ischemia by TUNEL; 24 hours after
      AMI, the hearts were isolated to determine the area of myocardial infarction by
      quantitative histological assay (triphenyltetrazolium chloride, TTC stain).
      RESULTS: Comparing with model group,the myocardial infarct size and apoptosis
      index of all the treatment groups decreased. Comparing with Guan-Xin-Er-Hao (30
      g/kg) or Dan-Chuan-Hong (10 g/kg), the myocardial infarct size and apoptosis
      index of Dan-Chuan-Hong (20 g/kg) had no statistic difference. And there was
      statistic difference between Guan-Xin-Er-Hao (30 g/kg)and Dan-Chuan-Hong (10
      g/kg). CONCLUSION: Comparing with Guan-Xin-Er-Hao, the decoction of Dan-Chuan
      Hong has similar effect, which could protect hearts from myocardial ischemia by
      inhibiting the myocardial apoptosis.

PMID- 19771847
TI  - [Regulation of protein kinases on signal pathway in breast cancer cell MCF-7 by
      curcumin].
AB  - OBJECTIVE: To observe the effect of curcumin on protein kinases on cell signal
      pathway in breast cancer cell MCF-7. METHODS: The suppressive effect of curcumin
      on MCF-7 cell proliferation as different concentration and at different time
      points were observed by MTT assay; The activity of p-ERK, p-NF-kappaB, p-p38 and
      p-JNK were observed by western blot. RESULTS: The suppressive effect of curcumin
      was shown as a dose dependent and a time dependent manner,and the IC50 was 22.48
      micromol/L 40 micromol/L curcumin inhibited the expression of p-ERK, p-NF-kappaB
      and p-p38, but not p-JNK. CONCLUSION: Curcumin can inhibit MCF-7 cell's
      proliferation, and its mechanism may be related to the activities of protein
      kinases on cell signal pathway.

PMID- 19771848
TI  - [Study on effects of curcumin on expressions of PDGF-BB, PDGFRbeta and ERK1 of
      HSC].
AB  - OBJECTIVE: To observe the effects of curcumin on expression of PDGF-BB, PDGFRbeta
      and ERK1 of rat Hepatic stellate cell (HSC-T6). METHODS: The cultured HSC were
      divided into control group, each curcumin treating group. The influence of
      curcumin on HSC proliferation was detected by MTT assay. The protein levels of
      PDGF-BB, PDGFRbeta and ERK1 was detected by immunhistochemical examination; The
      influence of curcumin on expression of PDGF-BB, PDGFRbeta and ERK1 mRNA was
      detected by RT-PCR. RESULTS: Immunohistiochemical results showed that normal
      cultured HSC-T6 cell expressed PDGF-BB, PDGFRbeta and ERK1 remarkably. After the
      intervention of different concentration of curcumin,the masculine degrees of PDGF
      BB, PDGFRbeta and ERK1 and the masculine cell population decreased obviously. The
      RT-PCR results indicated that the expressions of PDGF-BB, PDGFRbeta and ERK1 mRNA
      could be obviously seen in control and TGF-beta1 stimulus group. After the
      intervention of different concentration of curcumin, the expression of PDGF-BB,
      PDGFRbeta and ERK1 mRNA decreased in a dose-dependent manner. CONCLUSION:
      Curcumin could inhibit the expression of PDGF-BB, PDGFRbeta and ERK1 which might
      be the mechanism of action curcumin on anti-fibrosis.

PMID- 19771849
TI  - Comparison of the antioxidant activity amongst Gingko biloba extract and its main
      components.
AB  - OBJECTIVE: To compare the antioxidant activity amongst the extract of Ginkgo
      biloba (EGb) and its main components, flavonoids and terpenoids. METHODS: The
      induction of EGb, flavonoids and terpenoids on a typical antioxidant enzyme,
      glutamate cysteine ligase catalytic subunit (GCLC), in cell lines was detected by
      Western-blot. The effects of EGb, flavonoids and terpenoids on superoxide anion
      radical (O2*(-)), hydroxyl radical (OH*), rat erythrocyte hemolysis and lipid
      peroxidation of rat liver homogenate were determined by respective activity
      methods. RESULTS: EGb and flavonoids but not terpenoids were demonstrated
      significantly to induce the antioxidant enzyme (GCLC), directly scavenge O2*(-),
      OH* and inhibit rat erythrocyte hemolysis and lipid peroxidation of rat liver
      homogenate. Compared these antioxidant activities between EGb and flavonoids, the
      activities of flavonoids were weaker than those of EGb, which contains similar
      dose of flavonoids. CONCLUSION: EGb has stronger antioxidant activities than
      flavonoids, but terpenoids did not show antioxidant activity in this research.

PMID- 19771851
TI  - [Effect of Astragalus mongholicus injection on proliferation and apoptosis of
      hormone sensitive (MCF-7) breast cancer cell lines with physiological dose E2].
AB  - OBJECTIVE: To investigate the effect of Astragalus mongholicus injection on
      proliferation and apoptosis in hormone sensitive breast cancer cell lines (MCF-7)
      with physiological dose E2. METHODS: Cell control group, TAM control group and
      five different dose Astragalus mongholicus injection groups with physiological
      dose E2 were set in the study. Proliferation of MCF-7 cells were evaluated with
      MTT assay, cell apoptotic rate were measured with flow cytometry, DNA ladder and
      cell cycle were observed. RESULTS: In physiological dose E2, Astragalus
      mongholicus injection inhibited MCF-7 cells proliferation at all concentration
      groups. As time lasting, Astragalus mongholicus injection showed better
      inhibitory effect than TAM (P<0.05). Among 2 x 10(-1) g/mL-2 x 10(-4) g/mL
      concentration, Astragalus mongholicus injection significantly increased the
      proliferative percent of G0/G1 and S-phase cell, decreased percent of G2-M phase
      cell (P<0.05) at 24 hours. After cocultured 72 hours, Astragalus mongholicus
      injection increased the rate of apoptosis to 16.7% at 2 x 10(-1) g/mL
      concentration. CONCLUSION: In some dose limit, Astragalus mongholicus injection
      may inhibit proliferation, induce apoptosis and interrupt caryocinesia at G0-G1
      phase or S phase in hormone sensitive (MCF-7) breast cancer cell lines with
      physiological dose E2.

PMID- 19771850
TI  - [Flavonoids from Diospyros kaki inhibit the adhesion between lymphocyte and
      dorsal root ganglion].
AB  - OBJECTIVE: To investigate the effects of flavonoids from the leaves of Diospyros
      kaki L (FLDK) on the adhesion between the lymphocyte and the neurone. METHODS:
      Centrifugal assay for fluorescence-bsaed cell adhesion was used to assay the
      adhesion between the lymphocyte and the dorsal root ganglion (DRG). RESULTS: The
      adhesion was significantly suppressed in the presence of FLDK dose-dependently at
      5, 25 microg/mL concentration. FLDK was also effective to inhibit the adhesion
      under the challenge of ICAM-1 by 28.5% and 50.1%, respectively. Furthermore, FLDK
      enforced the inhibition of anti-NCAM antibody on the lymphocyte adhesion to DRG
      cells. CONCLUSION: FLDK might contribute to the prevention and treatment of the
      inflammation injury under neuron insult such as ischemia/reperfusion, neurotrauma
      and other neurodegenerative disease by inhibiting the adhesion between
      lymphocytes and neurons.

PMID- 19771852
TI  - [Effect of phospholipid composition on characteristics of liposomes containing
      zedoary turmeric oil].
AB  - OBJECTIVE: To study the effect of phospholipids composition on pharmaceutical
      characteristics of liposomes containing zedoary turmeric oil (ZTO). METHODS: The
      ZTO was extracted supersonically by solvent and then colored by sulfuric acid
      vanillin reagent. The ZTO liposomes were prepared by ethanol injection method. To
      determine the entrapment efficiency of the ZTO liposomes, we passed the liposome
      suspension through a Sephadex G-50 column equilibrated with PBS. Pharmaceutical
      characteristics of different liposomes such as size, zata potential, entrapment
      efficiency, stablility were determined and compared. RESULTS: The ZTO liposomes
      and free drug could be separated completely by the Sephadex G-50 chromatography,
      and the column recovery was (100.09+/-3.375)% (n=5). The ZTO liposomes composed
      of hydrogenated soybean phosphatidylcholine (HSPC) possessed the worst entrapment
      efficiency and sedimentation stability. The entrapment efficiency of the ZTO
      liposomes composed of soybean phosphatidylcholine (SPC) was equal to that of
      liposomes composed of both HSPC and SPC. However, The sedimentation and leakage
      stabilities of the latter were significantly higher than those of SPC liposomes.
      CONCLUSION: As the carrier of the ZTO liposomes, the composition of both HSPC and
      SPC can improve its stability.

PMID- 19771853
TI  - [Studies on purification of total saponins from the leaves of Acanthopanax
      trifoliatus by macroporous adsorption resin].
AB  - OBJECTIVE: To study the enrichment and purification of total saponins from the
      leaves of A. trifoliatus. METHODS: Using the total saponins from the leaves of A.
      trifoliantus as the standard index, we examinad the capability of static
      adsorption and desorption to select the optimum macroporous adsportion resin.
      Then we studied the purification technological parameters such as pH value, the
      dynamic adorption speed of flow, the best type quantity, the eluent density and
      so on. RESULTS: The optimum purification conditions were as follows: the type of
      macroporous adsorption resin was AB-8, the pH value of absorbing solution was 5
      6, the absorbing velocity of flow was 1.0 mL/min, the concentration of ethanol as
      elutent was 70%, the proportion of the amount of absorbing solution and resins
      was 4:1, the proportion of the amount of elutent and resins was 4:1, the eluting
      velocity of flow was 2.0 mL/min.

PMID- 19771854
TI  - [Purification of EGCG monomer from the extracts of tea by high speed
      countercurrent chromatography].
AB  - OBJECTIVE: To investigate the feasibility and techniques for purifying
      epigallocatechin-3-gallate (EGCG) by high speed countercurrent chromatography
      (HSCCC). METHODS: A HSCCC unit was used for the purification of EGCG from the
      extracts of tea. RESULTS: The preferable solvent system was composed of Ether
      Ethyl Acetate-H2O (4:10: 25, V/V), and the preferable technical conditions were
      as follows: the temperature was 35 degrees C, the rotation speed was 800 r/min
      and the mobile phase flow-rate was 2.5 mL/min. CONCLUSION: The purity of the
      obtained EGCG sample determined by high performance liquid chromatography (HPLC)
      is 95%.

PMID- 19771855
TI  - [Preparation technology of Zhangyanming dispersible tablet and determination of
      puerarin by HPLC].
AB  - OBJECTIVE: To study the extraction and pharmceutics technology of Zhangyanming
      dispersible tablet and establish the method for determining the content of
      puerarin by HPLC. METHODS: Using total extracted puerarin and disintegrating time
      as evaluation indexes and the conditions for determination were as follows:
      Hypersil BDS C18 column (5 microm, 4.6 mm x 200 mm), Methanol-H2O (25:75) as the
      mobile phase, the detection wavelength at 250 nm, the column temperature at 30
      degrees C, and 1.0 mL/min as the mobile phase speed. RESULTS: The calibration
      curve was linear at the range of 0.1699 to 1.3594 microg for the puerarin content
      and the linear equation was y = 3.054 x 10(6)x - 24019 (r = 0.9998). The average
      recovery ratio was 100.03%, and the relative standard deviation was 1.79%.
      CONCLUSIONS: The new preparation technology is reasonable and HPLC can be used to
      determine the content of puerarin in Zhangyanming dispersible tablet because the
      operation was convenient, fast, easy to repeat, and the analysis results were
      accurate and especial.

PMID- 19771856
TI  - [Characteristics of element contents and their influence factors in Codonopsis
      tangshen].
AB  - OBJECTIVE: To study the characteristics of element contents and the influencing
      factors in Codonopsis tangshen. METHOD: The contents of elements were determined
      and the data was statistically analyzed. RESULT: The variation coefficients of
      elements in C. tangshen were lower than those in soil, and variation coefficients
      of C. tangshen from different habitats were lower than 50%. CONCLUSION: The
      absorption of nutritional elements in C. tangshen was related to content and
      condition of soil nutrients, and climate etc.

PMID- 19771857
TI  - [Photosynthetic characteristics and chlorophy II fluorescence parameters of
      different populations of Pinellia ternata].
AB  - OBJECTIVE: To study the photosynthetic characteristics and chlorophyll
      fluorescence parameters of Pinellia ternate from different sources, in order to
      provide basis for cultivation and breeding. METHOD: Pigment contents were
      compared among different sources by the Lichtenthaler method. The light-response
      and diurnal photosynthesis course of P. ternata from different sources were
      analyzed by LI-6400 system, and chlorophll fluorescence parameters were analyzed
      by PAM-2100 system. RESULT: The difference of photosynthetic characteristics
      among the sources were remarkable. The light compensation point (LCP) of P.
      ternate from different sources were 11.57-17.88 micromol x m(-2) x s(-1), the
      light saturation point (LSP) were 1 000-1 300 micromol x m(-2) x (s-1). All the
      sources have obvious "midday depression". P. ternate cultivated in Xinjiang
      showed a higher light saturation point (LSP) and better chlorophyll fluorescence
      parameters. CONCLUSION: P. ternata cultivated in Xinjiang showed better
      photosynthetic characteristics and chlorophyll fluorescence parameters than the
      others.

PMID- 19771858
TI  - [Genetic relationship analysis of different provenances of Leonurus japonicus by
      ISSR marker].
AB  - OBJECTIVE: To study the genetic polymorphism and genetic relationship of
      different provenances of Leonurus japonicus. METHOD: Genetic relationship in 19
      provenances, which came from nationwide origins were measured by using polymerase
      chain reaction (PCR) with ISSR marker. RESULT: Twenty ISSR primers were selected
      from 100 ISSR primers and used for ISSR amplification. A total of 164 bands were
      generated, of which 117 bands were polymorphic bands (the percentage of
      polymorphic band, PPB = 71.34%). The similarity coefficients were calculated with
      NTsys 2.10e software and the dendrogram were constructed with UPGMA. Nineteen
      samples were divided into 3 types using the cluster analysis according to their
      genetic similarity coefficient. CONCLUSION: Results from the cluster analysis
      were correlated significantly with the morphological characteristics and
      geographical location of 19 samples. The data indicate that ISSR technique is
      useful to determine genetic diversity and genetic relationship among Leonurus
      provenances, providing a scientific basis for genetic breeding, differentiation
      and new cultivar selection.

PMID- 19771859
TI  - [Comparative study on yield and quality of flower buds of Lonicera japonica
      within several flowering stages].
AB  - OBJECTIVE: To investigate the quality and quantity changes of Flos Lonicerace
      during flowering stages in Hanzhong GAP base in order for properly harvesting and
      quality control. METHOD: The yield index of Flos lonicerace in four flowering
      stages was determined, and the contents of chlorogenic acid and the total
      flavonoid in the samples were determined by HPLC and the colorimetry,
      respectively. The volatile oils were extracted by the SFE-CO2 and the
      constituents were analyzed by GC-MS. RESULT: The yield in the first two flowering
      times was attributed to about more than 80% of total yield, and the number of
      flower buds for each plant in the first time was almost the same as the sum of
      the other three times. The drying rate of the three-site green flowers kept the
      highest during the first flowering time, and the drying rate of the two-site
      white flowers kept the highest during the second flowering time. The contents of
      chlorogenic acid and the total flavonoid in the first flowering time were higher
      than those in the second, and among them, the two-site white flowers kept the
      highest, about 3.5% and 13.2%, respectively. For the sample flowers in in the
      second flowering time, the three-site green flowers kept the highest level of
      chlorogenic acid and the total flavonoid, about 2.7% and 11.6%, respectively.
      From the volatile oil samples in the five periods of Flos lonicerace in the first
      flowering time, 19 components were identified by GC-MS. They were composed by
      three types of compounds, n-diolefines, fatty acids and steroids. Nonacosane and
      hentriacontane had the relatively higher amount with more than 40% and 20%,
      respectively. The relative contents of vitamine E were higher too, about 8.15% -
      10.43%. And, gamma-5-sitostene-3-ol, stigmasta-5,2-diene-3-ol and campesterol
      were also detected. Among these steroids, the relative contents of the first two
      were 4.90% - 6.9%, 1.06%- 4.10%, respectively. CONCLUSION: The flowering samples
      in the first two times were attributed to the most to the total yield. The
      samples of the two-site white flower and the whole-white flower had the higher
      comprehensive quality. The components of vitamine E and the steroids in the
      volatile oil need to be paid more attention.

PMID- 19771860
TI  - [Residuals of organochlorine pesticides and heavy metals in soil and water of
      planting base and Liriope muscari].
AB  - OBJECTIVE: To analyze the residuals of organochlorine pesticides and heavy metals
      in soil, water and Radix Liriopes from planting bases in Quanzhou city, and
      evaluate the quality of the herb. METHOD: GC method was applied to determine
      residuals of organochlorine pesticides, the contents of Pb, Cd, Cu, Cr, and As
      were determined by IPC. RESULT: The contents of residuals of organochlorine
      pesticides and heavy metals varied among the samples of soil, water and Radix
      liriopes, but all of the residuals met requirement of the national standard.
      CONCLUSION: Residuals of organochlorine pesticides and heavy metals in soil,
      water and Radix liriopes from planting bases in Quanzhou city were conformed to
      GAP.

PMID- 19771861
TI  - [Study on fast quality control in extracting process of Paeonia lactiflora using
      near infrared spectroscopy].
AB  - OBJECTIVE: To set up a novel method for fast analysis of active components in
      water extracting process of Paeonia lactiflora with near infrared spectroscopy
      (NIRS). METHOD: HPLC was used as the reference method to determine the content of
      Paeoniflorin and a multivariate calibration model based on PLS algorithm was
      developed to analyze the correlation between the spectra and the corresponding
      values determined by the reference method. RESULT: The correlation coefficient of
      the calibration model was 0.996 2, and the predicted coefficient was 0.989 5. The
      RMSEC and RMSEP were 0.109 g x L(-1) and 0.138 g x L(-1), respectively, and the
      RSEP was 5.6%. CONCLUSION: The method mentioned above is proved to be convenient,
      rapid and nondestructive, accurate and reliable, and is applicable for fast
      analysis and monitoring of active components in extraction process of traditional
      Chinese medicine.

PMID- 19771862
TI  - [Preparation and prescription of enteric coated pellets of Panax notoginseng
      saponins pellets].
AB  - OBJECTIVE: To prepare enteric coated pellets containing panax notoginseng
      saponins. METHOD: Panax notoginseng saponins loaded pellets were prepared by
      Extrusion-Spheronization method, and coated by Eudragit L30D-55 using Glatt fluid
      bed with the bottom spray process, central composite design was used to optimize
      the coating prescription. RESULT: The drug release of enteric coated pellets of
      panax notoginseng saponins pellets would be lower than 5% in 2 h in simulated
      gastric fluid, but reach above 85% in 3 h in simulated human gastroenteric
      environment. CONCLUSION: The enteric coated pellets of panax notoginseng saponins
      have good acid residence to avoid panax notoginseng saponins from degrading in
      gastric acid.

PMID- 19771863
TI  - [Comparson study of two types of constituents in seeds of Cassia obtusifolia
      before and after roasted].
AB  - OBJECTIVE: To establish methods of RP-HPLC respectively for content-determination
      of two types of constituents in the Cassia obtusifolia respectively, and tp
      determine the constituents between the raw and roasted seeds of C. obtusifolia in
      order to distinguish the difference of those seeds. METHOD: HPLC systems
      consisted of Alltima C18 (4.6 mm x 150 mm, 5 microm), column temperature at 30
      degrees C, flow rate of 1.0 mL x min(-1). Two different mobile phases and
      detection wavelengths: I , ACN-THF-0.1% H3 PO4 (17 : 3:80), 278 nm; II , MeOH
      0.1% H3PO4 (79:21), 254 nm. Analyzed and compared the content of the two types of
      constituents between the raw and roasted seeds of C. obtusifolia. RESULT: The
      calibrate curves of 5 constituents were linear (r > 0.999 7). The precision and
      repeatability were perfect (RSD < 1.6%, 1.8%). The samples were stabile during 24
      h. CONCLUSION: The study provide a better universal reference for evaluating and
      controlling the quality of C. obtusifolia pieces.

PMID- 19771864
TI  - [Preparation and characterization of solid dispersions of ginkgolides].
AB  - OBJECTIVE: To optimize the preparation process of solid dispersions of
      ginkgolides to improve the drug dissolution. METHOD: The influence of formulation
      and preparation technology on drug release from solid dispersions was
      investigated by single factor test. The X-ray diffraction analysis (XRD) and
      differential scanning calorimetry (DSC) were used to characterize the solid
      dispersions of ginkgolides. RESULT: The solubilization efficiency of solid
      dispersions using PVP k30 as carrier was better than that taking poloxamer 188 or
      HPMC as matrix. The results of XRD and DSC showed that ginkgolides existed in
      solid dispersion at amorphous form or solvates form. The dissolution rate of
      ginkgolide B in solid dispersion was increased dramatically compared with raw
      material. CONCLUSION: Solid dispersions could significantly improve solubility
      and dissolution rate of ginkgolides.

PMID- 19771865
TI  - [Ligans from branch of Hypericum petiolulatum].
AB  - OBJECTIVE: To investigate the chemical constituents of Hypericum petiolulatum.
      METHOD: The chemical constituents were isolated and purified by column
      chromatography on silica gel, macroporous adsorbent resin, Sephadex LH-20, and
      preparative HPLC. Structures of the compounds were identified by NMR and MS
      spectroscopic methods. RESULT: Nine lignans were obtained and their structures
      were elucidated as (-)-(2R, 3R)-1-O-feruloyl-8,8'-bisdihydrosiringenin (1), (-) 
      secoisolariciresinol 4-O-beta-D-glucopyrano-side (2), isolariciresinol-beta-4'-O
      beta-D-glucopyranoside (3), 5-methoxy-9beta-xylopyra-nosyl-(+) -isolariciresinol
      (4), (+) -lyoniresinol 2alpha-O-beta-D-xylopyranoside (5), 5-methoxy-9-beta
      xylopyranosyl-(-) -isolariciresinol (6), isolariciresinol 6a-O-beta-D-gluco-side
      (7), (+)-lyoniresinol 3alpha-O-beta-D-xylopyranoside (8) and 7-methoxy-5
      benzofuranpropanol 4'-O-beta-D-glucopyranoside (9). CONCLUSION: Coupound 1 was
      new and compounds 2-9 were obtained from the genus Hypericum for the first time.

PMID- 19771866
TI  - [Studies on antibacterial constituents of Discocleidion rufescens (2)].
AB  - OBJECTIVE: To screen effective constituents of Discocleidion rufescens against
      bacteria. METHOD: Compounds were isolated by bioassay-guided fractionation method
      with various chromatographic methods and their structures were determined by
      spectral analysis and chemical evidence. RESULT: Seven compounds were isolated
      from the Et2O and n-BuOH extracts and identified as 5,7-dihydroxy-4'-methoxy
      flavone (1), quercetin (2), apigenin-7-O-beta-D-glucopyranoside (3), apigenin-7-O
      neohesperidoside (4), luteolin-7-O-neohesperidoside (5), gallic acid (6) and beta
      daucosteol (7). CONCLUSION: Compounds 1-6 were isolated from genus Discocleidion
      for the first time and exhibited certain inhibitory activity against Escherichia
      coli. Compound 6 also showed antibacterial activity against Staphylococus aureus.

PMID- 19771867
TI  - [Flavones from Helichrysi flos syn].
AB  - OBJECTIVE: To study the chemical constituents of Helichrysi flos syn. METHOD: The
      chemical constituents were isolated by various methods of isolation (silica gel,
      ODS column chromatography and HPLC) and their structure were elucidated by the
      analysis of spectral data and chemical properties. RESULT: Seven flavone
      compounds were isolated from the MeOH extract of Helichrysi flos syn. The
      chemical structures were elucidated as quercetin-3-O-beta-D-glucopyranoside (1),
      apigenin-7-O-beta-D-gentiobioside (2), quercetin-3-O-rutinoside (3), apigenin
      7,4'-di-O-beta-D-glucopyranoside (4), kaempferol-3,4'-di-O-beta-D-glucopyranoside
      (5), quercetin-3,3'-di-O-beta-D-glucopyranoside (6), apigenin-7-O-beta-D
      glucopyranosiduronic acid methyl ester (7). CONCLUSION: Compounds 2, 4-7 were
      obtained from the genus Helichrysum for the first time.

PMID- 19771869
TI  - [Studies on comparison and classification of Angelica sinensis from different
      areas in Gansu province].
AB  - OBJECTIVE: To compare and classify the samples of Angelica sinensis from 36
      different areas in Gansu province. METHOD: The HPLC was used to detect samples,
      and the computer aided similarity evaluation was used to analyze the
      fingerprints. Similarity combined with principal component analysis (PCA) and
      multidimensional pattern recognition of Euclidean distance were used to compare
      and classify the samples of A. sinensis in different areas. RESULT: It was found
      that the quality of A. sinensis is closely related to the growth environment.
      CONCLUSION: This method could be used to classify the samples of A. sinensis from
      a variety of sources.

PMID- 19771868
TI  - [Determination of six active components in three species of genus Swertia by HPLC
      multiwavelength with detection].
AB  - OBJECTIVE: To develop an HPLC method for the quantification of six active
      components in three species (Swertia davidi, S. nervosa and S. mussotii) .
      METHOD: The determination was performed on a Hypersil BDS colunm (4. 6 mm x 200
      mm, 5 microm). Acetonitrile and 0.5% phosphoric acid solution were used as the
      mobile phases with a gradient elution. The flow rate was 1.0 mL x min(-1). The UV
      detection wavelength was at 240, 274, 325 and 334 nm. The column oven temperature
      was at 25 degrees C. RESULT: Six components were separated commendably in 60
      minutes. The calibration curves of swertiamarin, gentiopicroside,
      norswertianolin, swertianolin, demethylbellidifolin and bellidifolin were in good
      linearity over the range of 0.520-20.8, 0.202-8.06, 0.107-4.28, 0.097-3.86, 0.094
      3.77, 0.101-4.02 microg, respectively (r = 0.999 9). The average recoveries were
      98.7%, 98.1%, 98.3%, 98.8%, 98.1% and 98.6%, respectively, and the RSD were less
      than 3.0% (n = 6). CONCLUSION: The method is accurate,simple and reproducible,
      and can be used to control the quality of Swertia.

PMID- 19771870
TI  - [Contents of diterpenoid pigments in didifferent parts of fruit from Gardenia
      jasminoides].
AB  - OBJECTIVE: To compare the contents of diterpenoid pigments among the fruit, seed,
      and pericarp from Gardenia jasminoides. METHOD: The separation of Crocin 1,
      Crocin 2, Crocin 3 were carried out simultaneously on a Kromasil C18 column at 35
      degrees C with the methanol-acetonitrile-0.3% formic acid anhydrous in gradient
      elution as the mobile phrases. The detection wavelength was set at 440 nm and the
      flow rate was 1.0 mL x min(-1). RESULT: The obtained linearity of the three
      components was better over 0.999 5 and the average recoveries were 97.50%,
      98.76%, 97.67%, respectively. The results exhibited the remarkable variation
      among the different parts of the fruit. CONCLUSION: The contents of three
      constituents in seed were higher than in pericarp.

PMID- 19771871
TI  - [Chemical and biological studies on essential oil from Ficus tsiangii].
AB  - OBJECTIVE: To analyze the chemical components of the essential oil extracted from
      the bark of Ficus tsiangii. METHOD: The essential oil was extracted by water
      steam distillation and separated by GC capillary column chromatography. The
      components were quantitatively determined with normalization method and
      identified by GC-MS; Oxidation levels were used to study the antioxidation of the
      essential oil. Born turbidimetric method was applied to study the action of the
      the essential oil on rabbit platelet aggregation in vitro. RESULT: The oil rate
      of Ficus tsiangii was 0.097%. 198 chromatographic peaks were detected and 57
      compounds were identified, which were composed of 72.06% of the total essential
      oil. The highest ingredients in essential oil were fatty acids. The essential oil
      had no antioxidation and a weak inhibitory effect of the ADP-induced platelet
      aggregation. CONCLUSION: The chemical and biological data of the essential oil
      were reported for the first time.

PMID- 19771872
TI  - [Effects of chemical constituents of Crossostephium chinense on insulin secretion
      in rat islets in vitro].
AB  - OBJECTIVE: To investigate the effects of the chemical constituents of the whole
      herbs of Crossostephium chinense on insulin secretion in rat islets. METHOD:
      Islets were isolated from rat pancreata, cultured in vitro, and measured by color
      signals of dithizone stained digestion solution for detection of pancreatic
      islets. The morphological observation of islets was carried out by inverted
      microscope. The effects of test compounds, scopoletin (1), scopolin (2),
      tanacetin (3), quercetagetin-3,6,7-trimethylether (4) and 5-O-methyl-myo-inositol
      (5) isolated from the whole herbs of C. chinense, on the insulin secreting level
      from islets were compared with those of glybenclamide as a positive control
      substances, and the difference in insulin secreting level from islets between the
      presence and absence of test compounds was assayed. RESULT: There was no
      difference in basal insulin secretion before and after 2 h incubation period of
      rat islets. The islets treated with quercetagetin-3,6,7-trimethylether have about
      2-fold higher insulin secreting level (P < 0.01) compared a normal control group.
      The islets treated with 5-O-methyl-myo-inositol have about 1.5-fold higher
      insulin secreting level (P < 0.05) compared to a normal control group. Whereas
      the islets treated with scopoletin show about 1.9-fold lower basal insulin
      secreting level (P < 0.05) than a normal control group. CONCLUSION: In this paper
      the developed cultivation method of isolated pancreatic islets from rat can be
      used as a kind of islet-based drug screening model for diabetes mellitus in
      vitro. Quercetagetin-3,6,7-trimethylether and 5-O-methyl-myo-inositol could
      enhance rat islet insulin secretion and further in vivo studies are needed to
      clarify the nature of such an observation. However, scopletin suppress rat islet
      insulin secretion.

PMID- 19771873
TI  - [Studies on pharmacokinetics of nitidine chloride in rabbits].
AB  - OBJECTIVE: A high performance liquid chromatography (HPLC) method was developed
      to determine the concentration of nitidine chloride in plasma and successfully
      applied to study pharmacokinetics after i.v. administration in rabbits. METHOD:
      Twelve rabbits, randomized into 2 groups , were given i.v. at the dose of 4, 6 mg
      x kg(-1) respectively. Chloramphenicol was used as an internal standard. Nitidine
      chloride was extracted from plasma with ion pair reagent, and was determined by
      HPLC. RESULT: The calibration curves of nitidine chloride was linear in the range
      of 0.03-2.04 mg x L(-1). Its recoveries were more than 95%, intra-day and inter
      day precisions were lower than 6%. The concentration-time curve of nitidine
      chloride in rabbits after i.v. of 4 and 6 mg x kg(-1) were shown to fit a two
      compartment model, the main pharmacokinetic parameters showed no significant
      difference between the low and high dosage, and the AUC values are directly
      relative to doses. T1/2alpha were (5.46 +/- 0.89), (4.76 +/- 0.33) min
      respectively, T1/2beta were (263.33 +/- 16.4), (274.71 +/- 16.52) min
      respectively, AUC were (46.56 +/- 1.80), (69.19 +/- 2.30) microg x min(-1) x mL(
      1) respectively. CONCLUSION: It is first time to establish the HPLC method to
      determine the concentration of nitidine chloride in rabbits plasma. The method is
      sensitive, accurate and reproducible. It is first time to study the
      pharmacokinetic characters of nitidine chloride in rabbits after i.v.
      administration, the elimination of nitidine chloride is linear pharmacokinetics.

PMID- 19771874
TI  - [Effect of nobiletin on K562 cells xenograft in nude mice].
AB  - OBJECTIVE: To observe the inhibitory effect of citrus extract nobiletin on K562
      cells xenograft in nude mice and discuss its anticancer activity and mechanism.
      METHOD: The model of K562 cells xenograft was established in nude mice. Twenty
      five nude mice were divided to five groups. After 24 hrs of inoculation with K562
      tumor cells subcutaneously, 1% CMC-Na in the nude mice of model control group,
      nobiletin (12.5, 25, 50 mg x kg(-1)) in the nude mice of nobiletin groups and CTX
      (20 mg x kg(-1)) in positive control group were administered once every day. The
      nude mice were killed at 18th day-point of administration. The inhibitory rate of
      nobiletin on tumor was calculated according to the measured tumor weight.
      Immunohistochemistry assay was used to determine the effect of nobiletin on VEGF
      expression and MVD, and CAM assay was used to detect the effect of nobiletin on
      vessel regeneration. RESULT: Nobiletin have notable inhibition on K562 cells
      xenograft in nude mice comparing with model control group (P < 0.01), the
      inhibitory rate of nobiletin groups were 36% -58%. The results of
      immunohistochemical technology showed that the expression of VEGF in nobiletin
      groups decreased significantly comparing with the model control group (P < 0.05,
      P < 0.01, P < 0.01). Nobiletin could remarkably decrease the angiogenesis within
      tumor tissues. The expression of CD34 in nobiletin low dose group and high dose
      group was lower than that in model control group (P < 0.05, P < 0.01). The result
      of CAM indicated that 4 microg and 2 microg nobiletin could inhibit the new blood
      vessels of CAM (P < 0.01). CONCLUSION: Nobiletin inhibited the tumor growth and
      angiogenesis by reducing the VEGF expression of K562 cells xenograft in nude
      mice.

PMID- 19771875
TI  - [Effect of Chuanxiong Fangfeng Baizhi prescription on isolated rabbit basilar
      artery].
AB  - OBJECTIVE: To observe the effect of the main constituents and its combination
      from Chuanxiong Fangfeng Baizhi prescription on isolated rabbit basilar artery.
      METHOD: The isolated rabbit basilar artery rings were treated with 5 mmol x L(-1)
      KCl and 5-HT 2.4 x 10(-8) mol x L(-1), and by measuring the tension of basilar
      artery rings, the effect of the main constituents and its combination from
      Chunxiong Fangfeng Baizhi Prescription on vascular activity was observed. RESULT:
      Under pre-contractions of KCl 45 mmol x L(-1), ligustilide, ferulic acid,
      imperatorin and two constituent's combination have the vasodilatation effect on
      rabbit basilar artery rings white prim-o-glucosylcimifugin and 4'-O-beta-D
      glucosyl-5-o-methylvisamminol have no same action. The EC50 sequence is P2 <
      imperatorin < ligustilide < P1 (P < 0.05). And the same vasodilatation effect on
      rabbit isolated basilar artery rings evoked by 5-HT 2.4 x 10(-8) mol x L(-1) was
      found for two constituents' combination. CONCLUSION: Except prim-o
      glucosylcimifugin and 4'-O-beta-D-glucosyl-5-o-methylvisamminol, all samples have
      the vasodilatation effect on rabbit isolated basilar artery rings evoked by KCl
      and 5-HT, the vasodilatation effect of constituent's combination were better than
      any single constituent.

PMID- 19771876
TI  - [Effects of three C21 steroidal saponins from Cynanchum auriculatum on cell
      growth and cell cycle of human lung cancer A549 cells].
AB  - OBJECTIVE: To investigate the inhibition of three C2 steroidal saponins from
      Cynanchum auriculatum on the cell growth and cell cycle of human lung cancer A549
      cells. METHOD: A549 cells were exposed to three C21 steroidal saponins of
      different concentrations (5, 10, 20, 40, 60, 80, 100 micromol L(-1)) for 48
      hours. After 48 h, MTT assay was used to evaluate the inhibiting effects of three
      C21 steroidal saponins on the proliferation of the A549 cells. Exponential growth
      phase A549 cells were treated with 47, 34, 60 micromol x L(-1) of three C21
      steroidal saponins respectively for 12, 24, 48 h, then the changes of cell cycle
      were analyzed by flow cytometry. RESULT: The three C21 steroidal saponins could
      inhibit the growth of A549 cells in dose-dependent manner and IC50 is 46. 07 mol
      x L(-1), 33.02 mol x L(-1), 59.92 mol x L(-1) respectively. The cell cycle
      analysis showed that wilfoside C1N and wilfoside C3N increased the percentage of
      G0/G1 phase cells and decreased G2/M and S-phase cells while the proportion of
      cells in S-phase was lower and in G2/M phase the proportion was higher than
      control when the cells were cultivated with wilfoside K1N (P < 0.05, P < 0.01).
      CONCLUSION: Three C21 steroidal saponins could inhibit the proliferation of A549
      cells in dose-dependent manner and the mechanism may be related to its arresting
      the cell cycle.

PMID- 19771877
TI  - [Protective effect of 3'-methoxy puerarin on cerebral ischemic injury/
      reperfusion in rats].
AB  - OBJECTIVE: To observe the effect of 3'-methoxy puerarin on cerebral infarction
      volume and free radical change of focal cerebral ischemia-reperfusion injury in
      rats and discuss the protective effect of 3'-methoxy puerarin on the cerebral
      ischemic/ reperfusion injury. METHOD: The thread method was used to induce middle
      cerebral artery embolization, to establish the focal cerebral ischemia
      reperfusion model. Rats were divided into five groups: the sham and model group,
      the two-dose group (5, 10 mg x kg(-1) x d(-1)) of 3'-methoxy puerarin and
      nimodipine group (5 mg x kg(-1) x d(-1)). The behavior changes and volume of
      cerebral infarction were observed, and the leves of SOD and the content of MDA
      were measured. RESULT: 3'-methoxy puerarin could significantly improve the
      symptoms of neurological deficit and reduce the infarct volume, and increased SOD
      activity and reduced the content of MDA of cortex in cerebral ischemia
      reperfusion injury rat, the action of 10 mg x kg(-1) of 3'-methoxy puerarin is
      more remarkable. CONCLUSION: 3'-methoxy puerarin has protective effect on focal
      cerebral ischemia-reperfusion injury in rat.

PMID- 19771878
TI  - [Effects of oxymatrine on proliferation of HepG2 cells].
AB  - OBJECTIVE: To investigate the effects and the mechanisms on oxymatrine inhibiting
      proliferation of HepG2 cells. METHOD: HepG2 cells were exposured to oxymatrine,
      final concentrations of which were 0.1, 0.2, 0.3, 0.4, 0.5, 0.8, 1, 2, 5, 8, 10,
      15 g x L(-1) respectively, MTT method was used to determine the inhibiting
      effects of oxymatrine on HepG2 cells proliferation, followed by Haematoxylin and
      Eosin staining to observe the cell morphology. The expression of P53, Bcl-2 and
      Bax were further investigated by Immunohistochemical analysis. RESULT: Oxymatrine
      below dosage of 1 g x L(-1) showed the little inhibition effect on the HepG2
      cells proliferation and exhibited the significant inhibition effect from 1 to 8 g
      x L(-1) in both a time-and dose-dependent manner. Whereas the dosage was above 8
      g x L(-1), oxymatrine didn't showed the time- and dose-dependent relationship.
      The results of immunohistochemical analysis indicated that the expression of Bax
      obviously increased and that of Bcl-2 and P53 decreased. CONCLUSION: Oxymatrine
      could notably inhibit the HepG2 cells proliferation probably via upregulating the
      expression of the Bax and downregulating the expression of Bcl-2 and P53.

PMID- 19771879
TI  - [Absorption kinetics of atractylenolide I in intestines of rats].
AB  - OBJECTIVE: To investigate the absorption kinetics of atractylenolide I in
      intestines of rats and the influence of P-glycoprotein (P-gp) on the absorption.
      METHOD: The absorption kinetics was investigated using the method of in situ
      intestine absorption in rats and the samples were determined by HPLC. RESULT:
      Atractylenolide I is absorbed quite well at all segments of intestine in rats and
      no specific absorption was founded in different segment. When the concentration
      of perfusion solution was increased contrarily the absorption rate constant (Ka)
      kept at the same level. Compared Ka of three different concentration of perfusion
      solution with variance analysis method, Ka of atractylenolide I had no
      significant differences. But the Ka values were significently increased in the
      presence of P-gp inbibitor, verapamil or digoxin. CONCLUSION: Atractylenolide I
      can be classified into high penetrating drug. Passive diffusion dominates the
      absorptive transport behivior of atractylenolide I. Atractylenolide I can be
      absorbed in the whole intestinal segments and there is not a preferntial
      absorption zone in the intestine. The absorption and secretion of atractylenolide
      I are mediated by the efflux transport system, P-gp.

PMID- 19771880
TI  - [Effect of emodin on rejection of liver transplantation in rats].
AB  - OBJECTIVE: To investigate the mechanism of Emodin on the role of acute rejection
      in rat liver transplantation. METHOD: Forty-eight pairs of orthotopic liver
      transplantation model were established with inbred rats which were randomly
      divided into 3 groups: Control group (BN --> BN), acute rejection group (Lewis -
      > BN) and emodin group (Lewis --> BN). Six recipients in each group were randomly
      collected and contents of TNF-alpha and IL-10 in the peripheral blood were
      detected with ELISA on Day 1, 3, 5 and 7 separately after transplantation and
      histopathological evaluation was made to detect the differences among groups
      after the livers were taken out on day 7. The other 10 in each group were
      protected to evaluate the animation and life time. RESULT: The average meso-life
      time in emodin group (25.6 days) is significantly longer (P < 0.05) than acute
      rejection group (10.9 days). Compared with the acute rejection group, Emodin
      group shows up less rejection in the histopathological evaluation (P < 0.01),
      less TNF-alpha (P < 0.05) and a significant up-regulation of IL-10 in the
      peripheral blood (P < 0.05 after day 3). CONCLUSION: Emodin can inhibit the acute
      rejection of liver transplantation in rats model effectively and it may play the
      role with reduction of TNF-alpha and upregulation of IL-10.

PMID- 19771881
TI  - [Effect of P38MAPK signal transduction pathway on apoptosis of THP-1 induced by
      allicin].
AB  - OBJECTIVE: The objective of this paper was to study the change of P38MAPK and Fas
      in the apoptosis of THP-1 cells induced by allicin. METHOD: The proliferation
      inhibition rates of THP-1 cells after various treatments were examined by MTT
      assay. Apoptosis rate was determined with Annexin V- FITC/PI double staining by
      flow cytometry. The expression and distribution change of the phosphorylation
      p38MAPK (P-p38MAPK) were detected by immunohistochemical staining. The changes of
      P-p38 MAPK and Fas proteins were detected by Western blot. RESULT: The
      proliferations of leukemia cell line THP-1 are inhibited by allicin. MTT assay
      showed that allicin can inhibit the proliferation of the THP-1 cell, and the
      inhibition was dependent on both dose and time. The IC50 of 72 hours was 12.8 mg
      x L(-1). Apoptosis rate detected by Annexin V-FITC/PI was proportional to the
      concentration of the allicin. After the immunohistochemical staining test, the P
      p38MAPK was located in the cell nucleus and plasma, showing deep brown, when
      adding allicin to THP-1 cell. Western blot test showed that the P-p38MAPK
      proteins expression was proportional to the concentration of Allicin and was also
      dose dependent. The levels of P-p38MAPK in negative control group, 1/2 IC50 of 72
      hours group and IC50 of 72 hours group were 0.259 8 +/- 0.013 2, 0.61 2 +/- 0.008
      3 and 0.505 6 +/- 0.005 5 respectively, and the levels of Fas proteins were 0.287
      4 +/- 0.008 9, 0.426 8 +/- 0.007 9 and 0.597 1 +/- 0.010 9 respectively. The
      difference was statistically significant when compared with the negative control
      group (P < 0.01). CONCLUSION: Allicin can significantly induce THP-1 cells
      apoptosis, and its mechanism may be related to the activation of P38MAPK/Fas.

PMID- 19771882
TI  - [Advance on targets and drugs for anti-HIV].
AB  - As the spreading of AIDS over the world, to research effective anti-HIV drugs is
      required. The review contains the process of discovering targets for anti-HIV
      especially entry/infuse, reverse transcriptase, protease and integrase, and
      describes the effective component of traditional Chinese drugs for these targets
      and the anti-HIV drugs being researched or used in clinic.

PMID- 19771884
TI  - [Research on foreign countries laws and regulations on surveillance and reporting
      of postmarketing drugs adverse reactions].
AB  - Following more and more new drugs are authorized into market, new, serious or
      unexpected adverse drug reactions appear frequently, which is a serious threat to
      people health and life. Through making laws and guidelines, governments of
      various countries aim to strengthen and standardize the surveillance and
      reporting of postmarketing drugs. The drugs management department of our country
      are doing related jobs positively, but there are some problems, such as drug risk
      menagement is not emphasized well, and the management department lacks clarity on
      operating related regulations. This article tries to explore foreign countries'
      laws and regulations on the surveillance and reporting of postmarketing drugs,
      aiming to provide reference for our courtry.

PMID- 19771883
TI  - [Effect of entrainer on supercritical CO2 for extraction of tradition and herbal
      drugs].
AB  - Type, mode of affiliating, mechanism of action of entrainer in Supercritical CO2
      on extraction of Chinese traditional and herbal drugs were briefly reviewed.
      Application of entrainer in Supercritical CO2 on extraction of flavones,
      terpenes, sterols, and saponins in Chinese traditional and herbal drugs were
      recommended in particular. Some problems and directions in research of entrainer
      in Supercritical CO2 on extraction of Chinese traditional and herbal drugs were
      shown in this paper.

PMID- 19771885
TI  - [Patented technology status quo and development trend for Chinese herbal
      medicines].
AB  - Patent technology is regarded as technological trends under the market economy
      condition. The case showed the information form patent literature can be widely
      used in technology or economy. In this study, we analyzed the patent technology
      status quo and development trend for Chinese herbal medicines based on China
      patent database. The patent technology status quo is divided from the technology
      of biotechnology, quality control, cultivation and herb processing on Chinese
      herbal medicines. Furthermore, some recommendations of technology development and
      advices on patent protection for Chinese herbal medicines were suggested.

PMID- 19771886
TI  - [A new algorithm for ultrasound image speckle suppression].
AB  - Ultrasound image has a lot of speckle noise, which brings great difficulties to
      the feature extraction, recognition and analysis. Especially in the edge
      extraction, the conventional extraction algorithms are difficult to achieve the
      desired results because of the speckle noise. To solve this problem, an algorithm
      based on the anisotropic diffusion equation is presented. The new algorithm
      combines the robust estimation and considers the characteristic of the speckle
      noise, so it can suppress the speckle noise effectively and be more robust, thus
      the edge details of the ultrasound image can be preserved even enhanced, which
      can provide effective safeguard for the following edge extraction. Furthermore,
      the paper proposes a new method to compute speckle scale coefficients
      automatically, which reduces the influence of the human beings, and enhances the
      stability of the algorithm.

PMID- 19771887
TI  - [Adaptive de-noising of ECG signal based on stationary wavelet transform].
AB  - According to the limitations of wavelet threshold in de-noising method, we
      approached a combining algorithm of the stationary wavelet transform with
      adaptive filter. The stationary wavelet transformation can suppress Gibbs
      phenomena in traditional DWT effectively, and adaptive filter is introduced at
      the high scale wavelet coefficient of the stationary wavelet transformation. It
      would remove baseline wander and keep the shape of low frequency and low
      amplitude P wave, T wave and ST segment wave of ECG signal well. That is
      important for analyzing ECG signal of other feature information.

PMID- 19771888
TI  - [Development of a handy-type monitoring system for cardiovascular haemodynamic
      functions based on the volume-compensation and electrical admittance method].
AB  - A handy-type monitoring system for cardiovascular haemodynamic functions based on
      the volume-compensation and electrical admittance method is developed. In this
      system, the inconvenient and discomfort due to cuff occlusion of the biological
      segment for BP measurement is improved by developing a new device using a local
      pressurization method, the stability for the physiological information detection
      is improved by developing a new detecting system, and the noise during detection
      using the system is greatly reduced by using a newly developed nozzle-flapper
      type electro-pneumatic converter. Also, for electrical admittance cardiography to
      estimate CO, the applicability of a two-compartment coaxial cylindrical model and
      the optimal position of a spot-electrode array that is used to replace the
      conventional band-electrode are discussed in this research. Experimental result
      shows that the monitoring system should satisfy non-invasive BP and CO
      measurement on beat by beat, and the comfort of measurement is significantly
      improved.

PMID- 19771889
TI  - [Application of fingerprint identification technology in EMR system].
AB  - Based on the deep analysis of existing fingerprint identification algorithms,
      this article proposes an integrative solution to adopt the fingerprint
      identification technology into EMRS Electronic Medical Records System. It may
      improve the security of EMRS and raise the working efficiency of physicians
      effectively.

PMID- 19771890
TI  - [A method to automatically analyze and diagnose ambulatory ECG signals for
      telemonitoring system].
AB  - This paper proposes a method of automatic ECG analysis and arrhythmia diagnosis
      for telemonitoring system. A multi-buffer technique is applied to organize
      dispersive ECG data. Then, according to second order derivatives of ECG signals,
      peaks of R waves are automatically detected. Finally, real-time heart rhythm is
      decided by results of R wave detection. Tests prove that the proposed method is
      precise, efficient and stable to be applied in real-time ECG telemonitoring
      system.

PMID- 19771891
TI  - [A solution for display and processing of DICOM images in web PACS].
AB  - OBJECTIVE: Use the technique of Java Applet to realize the supporting of DICOM
      image in ordinary Web browser, thereby to expand the processing function of
      medical image. METHOD: First analyze the format of DICOM file and design a class
      which can acquire the pixels, then design two Applet classes, of which one is
      used to disposal the DICOM image, the other is used to display DICOM image that
      have been disposaled in the first Applet. They all embedded in the View page, and
      they communicate by Applet Context object. RESULT: The method designed in this
      paper can make users display and process DICOM images directly by using ordinary
      Web browser, which makes Web PACS not only have the advantages of B/S model, but
      also have the advantages of the C/S model. CONCLUSION: Java Applet is the key for
      expanding the Web browser's function in Web PACS, which provides a guideline to
      sharing of medical images.

PMID- 19771892
TI  - [Research on the illuminance characteristics of LED surguical luminaire].
AB  - The illuminance characteristics of LED (Lighting Emitting Diode) Surgical
      Luminaire is researched in this paper from the aspects of the LED Single-tube
      illumination analysis, LED arrays distribution and lighting design. The facula
      distribution characteristics of the LED prototype and multi-facet entirety
      reflection Surgical Luminaire is tested and compared according to the standards.
      The results of experimental show that LED prototype can fully meet the surgical
      illumination requirements, and the LED's own characteristics and further
      development will greatly broaden the space of medical lighting.

PMID- 19771893
TI  - [The design method of gradient coils in permanent MRI].
AB  - According to the features of the open permanent MRI system, this paper designs
      the gradient magnetic field, in which the designed parameters are optimized. The
      simulation experiments demonstrate the effectiveness of the algorithm.

PMID- 19771894
TI  - [Change data capture implementation in HIS].
AB  - The paper introduces the Change Data Capture based on change-track-table
      implementation in hospital information system. It improves efficiency of the
      change data capture and distribution in the data flat.

PMID- 19771895
TI  - [The design of no-power combination manual/foot control suction apparatus].
AB  - In this paper, one kind of suction apparatus is introduced, which could use
      manual, foot control and control combination. The design mentality, realization
      method, installation constitution and application method are also described. It
      is suitable to the nonmotile source condition and transportation situation,
      adapting easily to environment, and getting into favour with the medical staff
      and field first-aid personnel.

PMID- 19771896
TI  - [Development of detector for pulse and fill-liquid in one body].
AB  - This paper describes the principle of detector for pulse and fill-liquid in one
      body, which is used to detect the body pulse and the number of liquid-drop within
      one minute when filling liquid. The detector works exactly and rapidly. It makes
      doctors and nurses disentangle from the annoyed daily grinds.

PMID- 19771897
TI  - [The study on techniques for monitoring intraocular pressure].
AB  - This paper aims at providing an up-to-date review of principle and application of
      various tonometers, and analyzes the new techniques of diurnal IOP monitoring and
      design of sensor system abroad. Requirements and test methods for GB/T 14710-93.

PMID- 19771898
TI  - [Project about how to deal with the interrupted test of environmental test for
      medical electrical equipment].
AB  - The environmental test for medical electrical equipment may be interrupted by
      power cut or the equipment broken and so on. For the purpose of standard and
      valid testing, this paper puts forward a project about how to deal with the
      interrupted disposal of environmental test for medical electrical equipment. The
      project aims at the environmental requirements and test methods for GB/T 14710-
      93.

PMID- 19771899
TI  - [Medical devices adverse events and its preventive measures].
AB  - The text analyzes the reasons of medical devices adverse events occurrence from
      manufacturers, medical institutions and patients. To guard against the events,
      the medical institutions should put emphasis on check of purchasing, informed
      consent, technical permission, SOP performing, the safe of medical and enhance
      monitoring etc.

PMID- 19771900
TI  - [Guidelines on medical devices vigilance system of European Commission & its
      enlightenment to China].
AB  - This paper introduces the guidelines on medical devices vigilance system of
      European Commission and the duty of parties involved. It provides reference for
      establishing medical devices vigilance system and strengthening regulation of
      medical devices in our country.

PMID- 19771901
TI  - [The economic life span application of field work in the medical equipment
      management].
AB  - This text introduces the economic life span into the medical equipments
      management, and analyze the medical equipments relevant factors of the economic
      life span from two aspects, the analytical and economic life span settled in the
      medical equipments management.

PMID- 19771902
TI  - [Modeling and implementation method for the automatic biochemistry analyzer
      control system].
AB  - In this paper the system structure The automatic biochemistry analyzer is a
      necessary instrument for clinical diagnostics. First of is analyzed. The system
      problems description and the fundamental principles for dispatch are brought
      forward. Then this text puts emphasis on the modeling for the automatic
      biochemistry analyzer control system. The objects model and the communications
      model are put forward. Finally, the implementation method is designed. It
      indicates that the system based on the model has good performance.

PMID- 19771903
TI  - [Performance evaluation of Mindray BS-200 automatic biochemistry analyzer].
AB  - OBJECTIVE: To evaluate the main performance of BS-200 automatic biochemistry
      analyzer. METHODS: To evaluate the repeatability, linearity, precision and
      accurate Of the BS-200 automatic biochemistry analyzer by 8 items that contain
      all wavelength (ALT, GGT, Cl-, Cr, Glu, TP, Alb. APOA1. TBil), and carry on the
      contrast experiment with Hitachi 7170. RESULTS: The daytime run CV,within-run CV
      between-run CV and total CV are under 4.0%, the duplication is well, the accuracy
      is high, the linear scope is wide, and the contrast experiment correlation is
      good. CONCLUSION: This instrument each appraisal target is good, and worth in the
      small or middle-sized hospital promotion application.

PMID- 19771904
TI  - [Calculation of inspiratory tidal volume of Datex Ohmeda 7100 anesthetic
      machine].
AB  - According to the basic work principle of Datex Ohmeda 7100 anesthetic machine,
      the calculation formula of inspiratory tidal volume is deduced in the paper. The
      formula is verified by clinical application. The summary how to direct the
      applying and maintaining anesthetic machine and its monitoring instrument by
      using formula is presented.

PMID- 19771905
TI  - [Coblation for benign hyperplasia of tongue base under endoscope].
AB  - OBJECTIVE: To investigate the feasibility and efficacy of coblation on benign
      hyperplasia of tongue base under endoscopy. METHOD: Fifty cases with benign
      hyperplasia at tongue root including tonsillar hypertrophy, lymphangioma and
      papillary epithelioma were treated with coblation under endoscopy and analyzed
      retrospectively. The post-operative Hemorrhage and pain and therapeutic effect
      were observed. And the follow-up was 16 to 32 months. RESULT: All the tumors were
      resected completely. The postoperative pain was mild. The patients could eat on
      the day of surgery without dysfunction of pronunciation and respiratory. The VAS
      score of foreign body sensation in pharynx was decreased from 81.5 +/- 9.6 to
      13.5 +/- 3.9 after surgery (P < 0.01). The recovery rate was 96%, excellence rate
      was 4% and total effective rate was 100%. Besides, there was no recurrence.
      CONCLUSION: Coblation is a safe, effective and minimally invasive way to treat
      benign hyperplasia of tongue base under endoscopy.

PMID- 19771906
TI  - [Expression and significance of VEGF-C and VEGF-D in differentiated thyroid
      carcinoma].
AB  - OBJECTIVE: VEGF-C,D are known to be capable of inducing proliferation of
      lymphatic endothelia cell and development of lymphatic vessels, so we
      investigated the expression of VEGF-C,D in the differentiated thyroid carcinoma
      tissues microarray in order to understand the significance mechanism of cervix
      lymphatic metastasis of thyroid cancer. METHOD: A tissue microarray containing 71
      specimens was constructed, including normal thyroid tissues, thyroid adenoma,
      papillary thyroid carcinoma with and without lymphatic metastasis, follicular
      thyroid carcinoma. VEGF-C, D protein expression was detected with
      immunohistochemistry. RESULT: The expression of VEGF-C,D were not observed in
      normal thyroid tissues and adenoma tissues. The expression of VEGF-C,D in
      papillary thyroid carcinoma was significantly higher than those in follicular
      thyroid carcinoma (P < 0.05) and adeno ma tissues (P < 0.01). The expression of
      VEGF-C,D in papillary thyroid carcinoma with lymphatic metastasis was
      significantly higher than those in papillary thyroid carcinoma without lymphatic
      metastasis (P < 0.05). CONCLUSION: By inducing proliferation of lymphatic
      endothelia cell and development of lymphatic vessels, VEGF-C,D contributed to
      lymphatic metastasis of papillary thyroid carcinoma.

PMID- 19771907
TI  - [The anatomical study of the pterygopalatine fossa under endoscopy via the nasal
      cavity approach].
AB  - OBJECTIVE: To provide a basic anatomical study of clinical endoscopic surgical
      approach, we investigated the pterygopalatine fossa anatomy through lateral wall
      of the nasal cavity approach under endoscopy. METHOD: To observe important
      symbols and the neurovascular structure and its relations with the surrounding
      structure of pterygopalatine fossa, we dissect ten fresh cadaveric heads via
      lateral wall of the nasal cavity approach under endoscopy. RESULT: (1) The
      anatomical relations between pterygopalatine fossa and the surrounding structure
      were complicated, and internal maxillary artery and its branches were variate
      greatly. (2) Sphenopalatine foramen, infraorbital canal, foramen rotundum and
      pterygoid canal were the important symbol of bone of pterygopalatine fossa, and
      pterygopalatine fossa could be used as an access into the infratemporal fossa and
      sphenoid sinus. CONCLUSION: (1) An intimate knowledge of the constant anatomical
      symbols of the pterygopalatine fossa and the surrounding structure would maintain
      a sense of direction and improve surgery safety. (2) The pterygopalatine fossa
      could be exposed fully under endoscopy, and the vision was clear. Besides, the
      important nerves and vessels would be well protected, and operative approach was
      flexible according to the scope of pathological changes. (3) The near anatomic
      region could be accessed and the pathological changes could be treated through
      the endoscopic surgical approach.

PMID- 19771908
TI  - [The expression of oncogene AKT2 in laryngeal squamous cell carcinoma and its
      clinical significance].
AB  - OBJECTIVE: To investigate the expression and clinical significance of oncogene
      AKT2 in laryngeal squamous cell carcinoma (LSCC). METHOD: The expression of AKT2
      protein was measured with immunohistochemistry (Elivision two steps) in 60 cases
      of LSCC tissue, 28 cases of peri-cancer tissue and 16 cases of normal laryngeal
      epithelium, the relationship between AKT2 expression and clinical pathologic
      factors in LSCC was also analyzed. RESULT: The positive rates of AKT2 protein
      expression in LSCC and peri-cancer tissue were 56.7% (34/60), 14.3% (4/28)
      respectively. There was no expression of AKT2 in normal laryngeal epithelium. The
      positive rate of AKT2 protein expression in LSCC was significantly higher than
      that in peri-cancer tissue and normal laryngeal epithelium (P < 0.05,
      respectively). The positive rate of AKT2 was correlated with tumor site, lymph
      node metastasis and clinical stage of LSCC (P < 0.05, respectively), but wasn't
      correlated with patient's age, sex, and T stage (P > 0.05, respectively).
      CONCLUSION: AKT2 might play an important role in the tumorigenesis and
      development of LSCC, and it was suggested that AKT2 could be a useful marker for
      predicting tumorigenesis, invasion and metastasis potential of LSCC.

PMID- 19771909
TI  - [Bilateral effects of the pre- and postoperative septoplasty evaluated
      objectively with acoustic rhinometry and rhinomanometry].
AB  - OBJECTIVE: To evaluate effects of septoplasty on bilateral nasal cavities with
      acoustic rhinometry and rhinomanometry objectively. METHOD: Twenty-two patients
      who underwent septoplasty were examined with rhinomanometry and acoustic
      rhinometry before and 6 to 12 months after surgery. Of the 22 patients, 1 patient
      whose rhinomanometry and acoustic rhinometry datum were not available for the
      bilateral nasal obstruction, 3 patients with bilateral turbinectomy and 2
      patients with unilateral turbinectomy wide nasal cavities were excluded. Finally,
      18 narrow side nasal cavities and 16 wide side nasal cavities were analyzed.
      RESULT: Rhinomanometry: nasal resistance on the deviation side decreased
      significantly (P < 0.05), whereas on the contralateral side decreased slightly (P
      > 0.05). Acoustic Rhinometry: the predecongestion nasal minimal cross-sectional
      area (NMCA) and 0-5 cm NCV on the deviation side increased significantly due to
      the operation (P < 0.01). The corresponding postdecongestion increased were the
      same. Whereas on the contralateral side NMCA decreased and 0-5 cm NCV increased
      slightly before decongestion and after decongestion (P > 0.05). Only slight
      median increases were noted in the bilateral assessment postoperatively in NCV (P
      > 0.05) before and (P < 0.05) after decongestion. CONCLUSION: The nasal patency
      on the deviation side is undoubtedly increased after septoplasty, and the airway
      on the wide side is not worsened after the operation.

PMID- 19771910
TI  - [A case study on therapy for functional voice disorder of glottal dysraphism
      patient].
AB  - OBJECTIVE: To testify the effect of voice therapy methods for the glottal
      dysraphism patient with functional voice disorder. METHOD: The subject was a 62
      year old man, who had been diagnosed as functional voice disorder of glottal
      dysraphism. The main therapy was voice training, with normalized noise energy
      (NNE) as the assessment and monitoring parameter of the voice function. The datum
      of the baseline period and the treatment period were collected, and were analyzed
      with A-B Single-Subject Design in statistics. RESULT: NNE had been significantly
      decreased (P < 0.01) through the systematical voice training. CONCLUSION: Voice
      training had been the effective therapy for the glottal dysraphism patient with
      functional voice disorder.

PMID- 19771911
TI  - [Early local flap reconstruction in nasal defect due to severe infection after
      rhinoplasty].
AB  - OBJECTIVE: To explore the feasibility, option of surgical method and surgery
      opportunity of local flap reconstruction in nasal defects due to severe infection
      after rhinoplasty. METHOD: The clinical datum of eleven patients, who had 15
      cases of local flap reconstruction due to severe infection after rhinoplasty,
      were analyzed retrospectively. The lesions included defects of nasal dorsum,
      nasal tip and anterior-nare-vestibular fistula. Areas of defects ranged from 1.5
      cm x 1.2 cm to 2.0 cm x 2.5 cm and fistula diameters fell between 0.6 cm and 0.9
      cm. Based on the principal of nasal aesthetic sub-unit, nasal defects were
      restored with local flaps, such as nasal dorsum flaps, rhomboid flaps and nasal
      columella-tip flaps. The early changes and the maintenances of nasal contour
      after reconstruction were observed. RESULT: All 15 reconstructions were carried
      out 2 weeks after control of infection, and stage-I recovery was achieved in all
      the cases. In the follow-up periods from 4 to 27 months, all the flaps survived.
      only 2 cases had distortion of nasal tips, however, they were recovered with
      subcutaneous injection restoration; the other cases received satisfactory nasal
      contour where the flaps matched well with the neighbor skin in color, texture and
      extent of actinic dermatitis. CONCLUSION: Based on the principal of nasal
      aesthetic sub-unit, the individualized early local flap reconstruction would have
      good effect on nasal function and aesthetics, which will restore self-confidence
      of the patients as soon as possible.

PMID- 19771912
TI  - [Effects of c-Met-siRNA on the biological behaviour of laryngeal carcinoma Hep-2
      cells].
AB  - OBJECTIVE: To explore the effects of c-Met-siRNA on the proliferation, movement
      and invasion of laryngeal carcinoma Hep-2 cells in vitro. METHOD: Firstly, the
      pSilencer 2.0/c-Met-shRNA recombinant plasmid was transfected into laryngeal
      carcinoma Hep-2 cells with transfecting agent of cationic liposome Lipofectamine
      2000. Secondly,the transfection efficacy was tested by RT-PCR and Western-Blot,
      then the most inhibitive c-Met-siRNA sequence was elected. Cell proliferation,
      movement and invasion were detected with MTT, cell migration assay and cell
      invasion assay, respectively. RESULT: After the transfection of pSilencer 2.0/c
      Met-shRNA recombinant plasmid into laryngeal carcinoma Hep-2 cells, the
      expression of mRNA and protein of c-Met decreased significantly in Hep-2 cells,
      and ability of the proliferation, movement and invasion of laryngeal carcinoma
      Hep-2 cells were also inhibited. CONCLUSION: The results indicated that c-Met
      siRNA can down-regulated the expression of c-Met and markedly inhibited laryngeal
      carcinoma Hep-2 cell proliferation, movement and invasion. It may have the
      potential as a therapeutic modality to treat human laryngeal carcinoma.

PMID- 19771913
TI  - [Studies on the effects of Qi-boosting toxin-resolving decoction on proliferation
      of nasopharyngeal carcinoma cell].
AB  - OBJECTIVE: To investigate the effect of several traditional Chinese medicine
      formula therapies on proliferation of nasopharyngeal carcinoma cell line HNE1.
      METHOD: The inhibition effect of medicine serums of Qi-Boosting Toxin-Resolving
      granule on proliferation of NPC cell line HNE1 in vitro was observed by MTT
      assay. RESULT: The rates of survival cells in Qi-Boosting Toxin-Resolving
      decoction group and Toxin-Resolving group were the lowest after 48 hours
      treatment, while Qi-Boosting group, yin-nourishing group, residual-component
      group medicine serums had the most obvious effects on the rates of survival cells
      at 72 hours. The inhibition ratio of 15% Qi-Boosting Toxin-Resolving granule
      medicine serums was 67.68%. CONCLUSION: The result of MTT assay showed that cell
      proliferation was significantly inhibited by Qi-Boosting Toxin-Resolving granule
      and its separate composes medicine serums. Qi-Boosting Toxin-Resolving granule
      had the most significantly specific effects. The effects were correlated with
      serum concentration and treatment time of Qi-Boosting Toxin-Resolving granule and
      its separate composes medicine.

PMID- 19771914
TI  - [Comparison of two specific immunoglobulin E test systems in the diagnosis of
      allergic rhinitis].
AB  - OBJECTIVE: To evaluate the diagnostic performance of the AllergyScreen system
      from Mediwiss An alytic GmbH and the Pharmacia CAP system from Pharmacia
      Diagnostics for the detection of four inhalant allergens in the diagnosis of
      allergic rhinitis. METHOD: All 35 serum samples were collected from patients who
      were referred to the allergist for a suspected allergic rhinitis between January
      to March in 2007. Patients were classified as study diagnosis-positive for
      inhalant allergy if they both had a positive clinical examination/history and a
      related positive skin test for the suspected inhalant allergen. RESULT: Comparing
      with the reference standard, the diagnostic indexes (sensitivity, specificity,
      accuracy, predictive value of positive, and predictive value of negative) of the
      CAP system and the AllergyScreen system were 0.96 vs 0.89, 0.84 vs 0.75, 0.89 vs
      0.80, 0.78 vs 0.65 and 0.93 vs 0.93 respectively. The CAP system method had
      higher sensitivity, specificity and accuracy than AllergyScreen system method,
      but there have no statistical difference between two systems (P>0.05).
      CONCLUSION: This data support the use of ImmunoCAP system and AllergyScreen
      system to identify potentially significant individual allergens in the diagnosis
      of allergic rhinitis. The diagnostic indexes between the two systems have no
      statistical difference. As a simple, rapid turnaround time and low-cost system,
      AllergyScreen system can test multi-allergens in one time, so it can be used as a
      complementary with the ImmunoCAP system.

PMID- 19771915
TI  - [Revision endoscopic sinus surgery and combined therapy for recurrent sinusitis].
AB  - OBJECTIVE: To investigate the efficacy of revision endoscopic sinus surgery and
      combined therapy on recurrent sinusitis and polyps. METHOD: Revision endoscopic
      sinus surgery was performed in 72 patients, of which endoscopic nasal lateral
      wall dissection was used in 3 cases, the endoscopic frontal sinus surgery (Draf I
      II) was used in 16 cases, and all patients received combined therapy including
      peri-operation conservative management and nasal endoscopy examination during the
      follow-up period. RESULT: All patients were followed up for more than one year.
      Of 72 patients, 52 patients were successfully cured, 10 patients showed
      improvement, but there was no change in other 13 patients. The total efficacy
      rate was 91.67% (66/72). No serious complication occurred. CONCLUSION: The
      treatment efficacy can be greatly improved by enough preoperative preparation,
      fine operation, combined pre-operation conservative therapy and postoperative
      follow-up.

PMID- 19771916
TI  - [Clinical significance of CT examination in 197 cases of sinusitis].
AB  - OBJECTIVE: To analyze the characteristic of chronic paranasal sinusitis CT scans
      and discuss the relationship between the anatomic variations in ostiomeatal
      complex (OMC) and the incidence of chronic sinusitis. METHOD: One hundred and
      ninety-seven cases diagnosis as sinusitis were selected and analyzed,whose age
      ranged between 4 and 74 years old. Several common anatomical abnormalities in
      ostiomeatal complex were evaluated through the observation of the coronal and
      axial plane CT scans of the paranasal sinusitis. RESULT: The incidence of
      anatomic variations in OMC concentrated in the age between 11-20. The incidence
      of chronic sinusitis also concentrated in the age between 11-20. Deviation of
      nasal septum, uncinate variations, inferior-turbinate hypertrophy were observed
      between the chronic sinusitis group and the none chronic sinusitis group,the
      correlation between deviation of nasal septum, uncinate variations, inferior
      turbinate hypertrophy and chronic sinusitis were significant (P<0.05).
      CONCLUSION: The occurrence of OMC variation is common. The anatomic variations
      may be one of the causes of chronic paranasal sinusitis, especially deviation of
      nasal septum, uncinate variations and inferior-turbinate hypertrophy. If these
      abnormalities were altered,it will have a great significance for the preservation
      and treatment of chronic paranasal sinusitis.

PMID- 19771917
TI  - [Value of nasal endoscopy in the surgery of the nasal inverted papillomas].
AB  - OBJECTIVE: To evaluate the curative effect of endoscopic surgery (ESS) in the
      treatment of inverted papillomas in the nasal cavity and paranasal sinus. METHOD:
      We report on 16 clinicopathologic cases of inverted papilloma. After preoperative
      endoscopic examination and CT screening, endoscopic sinus surgery was performed
      under general anesthesia. RESULT: The follow-up period ranged between one year to
      two years. Recurrence was observed in 2 cases. CONCLUSION: The nasal endoscopy is
      a better method for treating Krouse I-II stage nasal inverted papilloma. The
      advantages of endoscopic surgery include clear visual field, less bleeding,
      limited reoccurrence, and avoidance of facial incision.

PMID- 19771918
TI  - [Efficacy of velopharyngoplasty for treating obstructive sleep apnea hypopnea
      syndrome].
AB  - OBJECTIVE: To investigate the indication, efficacy and influencing factors of
      velopharyngoplasty for treating of obstructive sleep apnea hypopnea syndrome
      (OSAHS). METHOD: Thirty OSAHS patients were included in this study, all cases had
      velopharyngoplasty. The follow-up period was between 6 to 11 months; and a series
      of measurements parameters was analysed for thirty cases. RESULT: When compared
      preoperatively and postoperatively, Apnea and hypopnea index (AHI) decreased from
      54.6+/-18.3 to 25.3+/-9.5; and the Epworth sleep scale decreased from 16.5+/-4.8
      to 5.2+/-4.1. According to related criterion in China, the effective rate was
      70.0%. CONCLUSION: Velopharyngoplasty can upgrade the venlopalate and enlarge the
      space of the oropharynx by remodeling of soft palate, contraction of scar and
      removal of the tonsils.

PMID- 19771919
TI  - [Selective neurotomy of anterior ethmoid nerve and squeezing operation of
      inferior turbinate for the treatment of perennial allergic rhinitis].
AB  - OBJECTIVE: To explore the treatment effect of selective neurotomy of anterior
      ethmoid nerve and squeezing operation of inferior turbinate in the treatment of
      perennial allergic rhinitis (PAR). METHOD: Seventy cases of perennial allergic
      rhinitis were selected and subjected to selective neurotomy of anterior ethmoid
      nerve and squeezing operation of inferior turbinate,and the treatment effect was
      observed by analysis of the the symptoms and signs score of all cases
      preoperatively and postoperatively. RESULT: The total effective rate were 90.0%
      at 1 year follow-up. CONCLUSION: Selective neurotomy of anterior ethmoid nerve
      and squeezing operation of inferior turbinate were effective for the patients
      with PAR. It is worthy to be popularized for its convent and rare complications.

PMID- 19771920
TI  - [Discussion on security of fiber nasopharyngeal laryngoscope for children].
AB  - OBJECTIVE: To study the factors of complications and the incidence rates after
      the examination of fiber nasopharyngeal laryngoscope. METHOD: To observe the
      complications appeared within 24 hours during and after fiber nasopharyngeal
      laryngoscope examination for 5000 children. RESULT: Of 5000 cases, 305 cases
      (6.10%) occurred transient complications during and after the operation. The
      incidence of complications in different age groups (0-1, >1-3, >3-7, >7-16) were
      9.83%, 6.14%, 3.15%, 1.69% respectively. It was significantly lower in older age
      groups compared with younger ones. The commonest complication was mucous membrane
      bleeding during the operation, which often occurred in infants and reduced by
      increasing age. Cough and cough deterioration often occurred after the operation
      and shortness of breath appeared in infants only. The differences were
      statistically significant. CONCLUSION: Pediatric fiber nasopharyngeal
      laryngoscope examination is safe and reliable and most of the complications were
      minor. Infants and children with laryngeal cartilage softening is high-risk
      factors for complications.

PMID- 19771921
TI  - [Clinical study on the treatment of juvenile recurrent laryngeal papilloma].
AB  - OBJECTIVE: To study and evaluate the feasibility and effect of the treatment for
      juvenile recurrent laryngeal papilloma by nasal endoscopy electric suction
      cutting and laser surgery. METHOD: The clinical data of 26 cases with juvenile
      recurrent laryngeal papilloma from 2002-2007 years were retrospectively analyzed.
      Six cases were treated by electric suction cutting under nasal endoscopy, 20
      cases were treated by electric suction cutting under nasal endoscopy and
      synergizing laser, and postoperative wound with sodium hyaluronate gel treatment.
      RESULT: The juvenile recurrent laryngeal papilloma were only operated by electric
      suction cutting with nasal endoscopy, laryngeal papilloma relapsed with
      fibrolaryngoscope examination at 4 weeks after operation, and were operated again
      during 2 to 3 months. The juvenile recurrent laryngeal papilloma were treated by
      electric suction cutting synergies laser treatment with the help of nasal
      endoscopy, and they were also treated repeatedly with laser at 2 or 3 weeks after
      operation. Sixteen cases cured perfectly with no reappearance after an 3 to 8
      years follow up, and the other 4 cases showed the prolongation of recurrence
      interval. CONCLUSION: Electric suction synergy laser treatment could effectively
      reduce the recurrence of the laryngeal papilloma, and it also needs laser
      treatment several times after operation to improve the treatment effect. The
      sodium hyaluronate gel is adopted on the wound of vocal cords, it can avoid the
      vocal cords scar and adhesion, and improve the quality of pronunciation. Some
      patients can be cured by this treatment method, and it should be advocated in the
      clinical work.

PMID- 19771922
TI  - [Expression and significance of VCAM-1 in subjects with allergic inflammation of
      respiratory tract].
AB  - OBJECTIVE: To study the expression and significance of vascular cell adhesion
      molecule-1 (VCAM-1) in subjects with allergic inflammation of respiratory tract.
      METHOD: Thirty-nine subjects with allergic rhinitis and asthma (allergic rhinitis
      and asthma group) and twenty-one subjects with only allergic rhinitis (allergic
      rhinitis group) were divided into two group. Bronchial and nasal biopsy specimens
      were taken and were stained with HE. The expression of VCAM-1 in nasal and
      bronchial mucosa was detected by immunohistochemistry technique. RESULT: The
      amounts of eosinophils within bronchial mucosa of allergic rhinitis and asthma
      group were significantly higher than that of allergic rhinitis group (t=12.81,
      P<0.01). The difference of VCAM-1 expression between allergic rhinitis group and
      allergic rhinitis and asthma group was not statistically significant . The
      amounts of VCAM-1 positive cell in bronchial mucosa of allergic rhinitis and
      asthma group were significantly higher than that of allergic rhinitis group
      (t=9.43, P<0.01). The number of VCAM-1 positive cells in bronchial mucosa was
      significantly positively correlated with the number of eosinophils in bronchial
      mucosa of allergic rhinitis and asthma group (r=0.783, P<0.01). CONCLUSION: This
      study shows that upregulation of VCAM results in generalized airway inflammation
      in patients with allergic rhinitis.

PMID- 19771923
TI  - [Expression of NR2A in rat auditory cortex after sound insulation and auditory
      plasticity].
AB  - OBJECTIVE: To study the changes of N-methyl-D-aspartate (NMDA) receptor subunit
      2A (NR2A) expression at local synapses in auditory cortices after early postnatal
      sound insulation and tone exposure. METHOD: We prepared highly purified
      synaptosomes from primary auditory cortex by Optiprep flotation gradient
      centrifugations, and compared the differences of NR2A expression in sound
      insulation PND14, PND28, PND42 and Tone exposure after sound insulation for 7
      days by Western blotting. RESULT: The results showed that the NR2A protein
      expression of PND14 and PND28 decreased significantly (P<0.05). Tone exposure
      after sound insulation for 7 days, mSIe NR2A protein level increased
      significantly (P<0.05). It showed bidirectional regulation of NR2A protein. No
      significant effects of sound insulation and lone exposure were found on the
      relative expression level of NR2A of PND42 (P>0.05). CONCLUSION: The results
      indicate that sound insulation and experience can modify the protein expression
      level of NR2A during the critical period of rat postnatal development. These
      findings provide important data for the study on the mechanisms of the
      developmental plasticity of sensory functions.

PMID- 19771924
TI  - Healthcare reform.

PMID- 19771925
TI  - Integrative pediatrics: the future is now.

PMID- 19771926
TI  - Could health coaching build a bridge to a new system of healthcare?

PMID- 19771927
TI  - Finding the money for healthcare reform.

PMID- 19771929
TI  - Effects of yoga on inner-city children's well-being: a pilot study.
AB  - OBJECTIVE: To examine yoga's effects on inner-city children's well-being.
      METHODS: This pilot study compared fourth- and fifth-grade students at 2 after
      school programs in Bronx, New York. One program offered yoga 1 hour per week for
      12 weeks (yoga) and the other program (non-yoga) did not. Preintervention and
      postintervention emotional well-being was assessed by Harter's Global Self-Worth
      and Physical Appearance subscales, which were the study's primary outcome
      measures. Secondary outcomes included other measures of emotional well-being
      assessed by 2 new scales: Perceptions of Physical Health and Yoga Teachings
      (including Negative Behaviors, Positive Behaviors, and Focusing/relaxation
      subscales). Preintervention and postintervention, physical wellbeing was assessed
      by measures of flexibility and balance. Subjective ratings ofyoga's effects on
      well-being were evaluated by an additional questionnaire completed by the yoga
      group only. RESULTS: Data were collected from 78% (n=39) and 86.5% (n=32) of
      potential yoga and non-yoga study enrollees. No differences in baseline
      demographics were found. Controlling for preintervention well-being differences
      using analysis of covariance, we found that children in the yoga group had better
      postintervention Negative Behaviors scores and balance than the non-yoga group (P
      < .05). The majority of children participating in yoga reported enhanced
      wellbeing, as reflected by perceived improvements in behaviors directly targeted
      by yoga (e.g., strength, flexibility, balance). CONCLUSIONS: Although no
      significant differences were found in the study's primary outcomes (global self
      worth and perceptions of physical well-being), children participating in yoga
      reported using fewer negative behaviors in response to stress and had better
      balance than a comparison group. Improvements in wellbeing, specifically in
      behaviors directly targeted by yoga, were reported. These results suggest a
      possible role of yoga as a preventive intervention as well as a means of
      improving children's perceived well-being.

PMID- 19771930
TI  - Shiatsu as an adjuvant therapy for schizophrenia: an open-label pilot study.
AB  - CONTEXT: Studies have suggested a possible role for shiatsu in treating a variety
      of mental and physical ailments. OBJECTIVE: To determine if shiatsu can provide
      clinical benefit to individuals diagnosed with schizophrenia. DESIGN: An open
      label pilot study. SETTING: An inpatient psychiatric ward at Herzog Memorial
      Hospital, Jerusalem, Israel. PATIENTS: Twelve hospitalized patients with chronic
      schizophrenia. INTERVENTION: Shiatsu treatment provided in a course of eight 40
      minute biweekly sessions over 4 weeks. MAIN OUTCOME MEASURES: All subjects were
      evaluated at baseline, 2 weeks, 4 weeks (end of treatment), and 12 weeks
      (followup). The tools used for assessment included the Clinical Global Impression
      (CGI), the Brief Psychiatric Rating Scale (BPRS), the Positive and Negative
      Syndrome Scale (PANSS), the Hamilton Rating Scale for Depression (HAM-D), the
      Hamilton Anxiety Rating Scale (HAM-A), and the Nurses' Observation Scale for
      Inpatient Evaluation (NOSIE). Side effects were measured using the Simpson-Angus
      Scale for Extrapyramidal Symptoms (SAS) and the Abnormal Involuntary Movement
      Scale (AIMS). RESULTS: On all scales of psychopathology and side effects, the
      subjects showed a statistically and clinically significant improvement by the end
      of treatment. This improvement was maintained at the 12-week follow-up. These
      findings, while encouraging, must be considered preliminary and require
      confirmation and cross-validation in larger-scale controlled studies.

PMID- 19771928
TI  - Factors associated with potential medication-herb/natural product interactions in
      a rural community.
AB  - CONTEXT: Use of both conventional medicines and herbs/natural products are
      increasing in the United States. Consequently, individuals are more likely to be
      exposed to potentially harmful interactions between these products. OBJECTIVE: To
      examine the use of both herbs/natural products and conventional medications in a
      rural community, examine the prevalence of potential interactions between
      herbs/natural products and conventional medications, and identify factors
      associated with exposure to such interactions. DESIGN: Population-based
      epidemiological study. SETTING: Data for this paper were collected between 1999
      and 2004 as part of the Johnston County Osteoarthritis Project. PARTICIPANTS:
      Limited to civilian, noninstitutionalized, white or African American residents,
      aged 45 years or older, of Johnston County, North Carolina. Data used in this
      paper are from 2523 individuals who completed face-to-face interviews. MAIN
      OUTCOME MEASURES: Prevalence of herb/natural product use and exposure to
      potential interactions between these products and conventional medications.
      RESULTS: Nineteen percent (n=488) of participants used at least 1 herb/natural
      product. Among those who used both conventional medications and herbs/natural
      products, more than 1 in 5 (97 [21.9%]) were using a combination of products
      associated with a potential interaction. Odds of exposure to a potential
      interaction were lower among people who had health insurance and increased with
      the number of products used. CONCLUSIONS: Many people are exposed to potential
      interactions between herbs/natural products and conventional medications.
      Research is needed to better understand the effect such interactions may have on
      patient care.

PMID- 19771931
TI  - Integrative approaches to pediatric mood disorders.
AB  - Mood disorders represent an increasingly common clinical challenge in pediatric
      care. The movement to an integrative approach provides many benefits. First, the
      emphasis is on the holistic assessment of the whole child or teen. As we embrace
      the ecological nature of human existence, this broad perspective enables us to
      see the child more comprehensively and thus to treat him or her more effectively.
      This allows us to grasp the barriers, triggers, strengths, and challenges for
      each young person. The integrative practitioner focuses more on symptom pattern
      than on DSM diagnosis. A whole-child approach naturally de-emphasizes labels and
      limitations of our diagnostic system. We can fully support the self-healing
      capacity of the child's ecosystem as it relates to body, mind, and spirit. The
      integrative practitioner actively seeks to avoid risky and unproven
      pharmacological interventions if possible..,This more cautious and natural
      approach is desired by many parents who embrace the holistic-integrative
      philosophy. This can be thought of as a significant and growing American
      subculture. As culturally sensitive practitioners, it is crucial that we work
      with children, teens, families, and parents within their belief systems. The last
      2 decades have seen a dramatic rise in the number of children given psychiatric
      medications. If current rates persist, within a generation, half of American
      children will be taking psychiatric medication. Many reasons for this pattern
      exist. Integrative practitioners can offer a variety of safe and effective
      alternatives for the child or teen struggling with a mood disorder. The greatest
      benefit comes from seeing a child fulfill his or her true potential.

PMID- 19771932
TI  - Migraines and mood disorders: nutritional and dietary intervention based on
      laboratory testing.

PMID- 19771933
TI  - Recurrent miscarriage syndrome treated with acupuncture and an allergy
      elimination/desensitization technique.

PMID- 19771934
TI  - Susan Frampton, PhD: Expanding the reach of patient-centered care. Interview by
      Frank Lampe and Suzanne Snyder.

PMID- 19771935
TI  - Tobacco under the FDA: a summary of the Family Smoking Prevention and Tobacco
      Control Act.

PMID- 19771936
TI  - Enabling alcohol and drug abuse in the workplace.

PMID- 19771937
TI  - Nursing and entrepreneurship: perfect together.

PMID- 19771938
TI  - Revisiting Das Gupta: refinement and extension of standardization and
      decomposition.
AB  - Standardization and decomposition are established and widely used demographic
      techniques for comparing rates and means between groups with differences in
      composition. The difference in rates and means has heretofore been resolved in
      terms of the contribution of variables to compositional effects for each variable
      and an overall rate effect. This study demonstrates that the resolution of
      differences is attainable at the categorical level for both compositional effects
      and rate effects. Refinements to Das Gupta's equations yield a complete
      decomposition because of the additivity of categorical compositional and rate
      effects. Other refinements allow the decomposition of polytomous variables.
      Extensions to the method provide for the decomposition of the standard deviation
      and the multivariate index of dissimilarity.

PMID- 19771939
TI  - Family allowances and fertility: socioeconomic differences.
AB  - This article explores socioeconomic differences in the effect of family
      allowances on fertility. Although several studies have examined the relationship
      between cash benefits and fertility, few studies have addressed the possible
      differential effects of cash benefits on families of different income or
      education levels. I reconstructed the birth histories of women in the past two
      Israeli censuses of 1983 and 1995 to study socioeconomic differences in the
      effect of family allowances up to the seventh parity. The results indicate that
      family allowances have a significant effect at every parity. Using female
      education as an indicator of socioeconomic status, I find that socioeconomic
      status is a significant modifier of the effect of family allowances. Family
      allowances seem to have a relatively large impact on more-educated women.

PMID- 19771940
TI  - Employment gains and wage declines: the erosion of black women's relative wages
      since 1980.
AB  - Public policy initiatives in the 1950s and 1960s, including Affirmative Action
      and Equal Employment Opportunity law, helped mitigate explicit discrimination in
      pay, and the expansion of higher education and training programs have advanced
      the employment fortunes of many American women. By the early 1980s, some scholars
      proclaimed near equity in pay between black and white women, particularly among
      young and highly skilled workers. More recent policy initiatives and labor market
      conditions have been arguably less progressive for black women's employment and
      earnings: through the 1980s, 1990s, and the first half of the 2000s, the wage gap
      between black and white women widened considerably. Using data from the Current
      Population Survey Merged Outgoing Rotation Group (CPS-MORG), this article
      documents the racial wage gap among women in the United States from 1979 to 2005.
      We investigate how demographic and labor market conditions influence employment
      and wage inequality among black and white women over the period. Although shifts
      in labor supply influence the magnitude of the black-white wage gap among women,
      structural disadvantages faced by black women help explain the growth in the
      racial wage gap.

PMID- 19771941
TI  - Job opportunities, economic resources, and the postsecondary destinations of
      American youth.
AB  - Using a nationally representative sample of graduates from the high school class
      of 2003-2004, I test the warehouse hypothesis, which contends that youth are more
      likely to leave school and enter the labor force when there are available job
      opportunities (and vice versa). Using two measures of job opportunities--local
      unemployment rates and the percentage of local workers employed in jobs that
      require a bachelor's degree--I find support for the warehouse hypothesis. In
      areas where unemployment is low, with ample jobs that do not require a bachelor's
      degree, youth have higher odds of entering the labor force. In areas where
      unemployment is high, with few jobs that require only a high school diploma,
      youth have higher odds of entering college. The effect of unemployment on
      enrollment is more pronounced for low-income youth than for high-income youth,
      with both low- and high-income youth turning to four-year schools rather than two
      year schools when job opportunities are limited.

PMID- 19771942
TI  - Parental characteristics and the schooling progress of the children of immigrant
      and U.S.-born blacks.
AB  - In this study, I examine disparities in schooling progress among children born to
      immigrant and U.S.-born blacks. I find that in one- and two-parent families,
      children born to black immigrants are less likely to fall behind in school than
      those born to U.S.-born blacks. In two-parent immigrant families, children born
      to two immigrant parents have a significant schooling advantage over children
      born to one immigrant parent. While children born to two immigrant parents in the
      wealthiest black immigrant families do better in the second generation than in
      the first, the reverse is observed among children in less wealthy families. These
      findings contribute in two ways to our understanding of the assimilation
      processes of children born to black immigrant parents. First, they show that
      there is a positive association between the number of immigrant parents in a
      family and children's schooling performance. Second, they suggest that
      disparities in the assimilation patterns of the children of black immigrants are
      a likely product of the interaction between their parental characteristics and
      the socioeconomic circumstances of their families.

PMID- 19771943
TI  - Do immigrants work in riskier jobs?
AB  - Recent media and government reports suggest that immigrants are more likely to
      hold jobs with poor working conditions than U.S.-born workers, perhaps because
      immigrants work in jobs that "natives don't want." Despite this widespread view,
      earlier studies have not found immigrants to be in riskier jobs than natives.
      This study combines individual-level data from the 2003-2005 American Community
      Survey with Bureau of Labor Statistics data on work-related injuries and
      fatalities to take afresh look at whether foreign-born workers are employed in
      more dangerous jobs. The results indicate that immigrants are in fact more likely
      to work in risky jobs than U.S.-born workers, partly due to differences in
      average characteristics, such as immigrants' lower English-language ability and
      educational attainment.

PMID- 19771944
TI  - Consequences of family disruption on children's educational outcomes in Norway.
AB  - Using high-quality data from Norwegian population registers, we examine the
      relationship between family disruption and children's educational outcomes. We
      distinguish between disruptions caused by parental divorce and paternal death
      and, using a simultaneous equation model, pay particular attention to selection
      bias in the effect of divorce. We also allow for the possibility that disruption
      may have different effects at different stages of a child's educational career.
      Our results suggest that selection on time-invariant maternal characteristics is
      important and works to overstate the effects of divorce on a child's chances of
      continuing in education. Nevertheless, the experience of marital breakdown during
      childhood is associated with lower levels of education, and the effect weakens
      with the child's age at disruption. The effects of divorce are most pronounced
      for the transitions during or just beyond the high school level. In models that
      do not allow for selection, children who experienced a father's death appear less
      disadvantaged than children whose parents divorced. After we control for
      selection, however differences in the educational qualifications of children from
      divorced and bereaved families narrow substantially and, at mean ages of divorce,
      are almost non-existent.

PMID- 19771945
TI  - Forced migration and mortality in the very long term: did perestroika affect
      death rates also in Finland?
AB  - In this article, we analyze mortality rates of Finns born in areas that were
      ceded to the Soviet Union after World War II and from which the entire population
      was evacuated. These internally displaced persons are observed during the period
      1971-2004 and compared with people born in the same region but on the adjacent
      side of the new border. We find that in the 1970s and 1980s, the forced migrants
      had mortality rates that were on par with those of people in the comparison
      group. In the late 1980s, the mortality risk of internally displaced men
      increased by 20% in relation to the expected time trend. This deviation, which
      manifests particularly in cardiovascular mortality, coincides with perestroika
      and the demise of the Soviet Union, which were events that resulted in an intense
      debate in civil society about restitution of the ceded areas. Because state
      actors were reluctant to engage, the debate declined after some few years, and
      after the mid-1990s, the death risk again approached the long-term trend. Our
      findings indicate that when internally displaced persons must adjust to
      situations for which appropriate coping behaviors are unknown, psychosocial
      stress might arise several decades after their evacuation.

PMID- 19771947
TI  - Investigating the mechanism of marital mortality reduction: the transition to
      widowhood and quality of health care.
AB  - While it is well known that the widowed suffer increased mortality risks, the
      mechanism of this survival disadvantage is still under investigation. In this
      article, we examine the quality of health care as a possible link between
      widowhood and mortality using a unique data set of 475,313 elderly couples who
      were followed up for up to nine years. We address whether the transition to
      widowhood affects the quality of care that individuals receive and explore the
      extent to which these changes mediate the elevated mortality hazard for the
      widowed. We analyze six established measures of quality of health care in a fixed
      effect framework to account for unobserved heterogeneity. Caregiving and acute
      bereavement during the transition to widowhood appear to distract individuals
      from taking care of their own health care needs in the short run. However, being
      widowed does not have long-term detrimental effects on individuals' ability to
      sustain contact with the formal medical system. Moreover, the short-run
      disruption does not mediate the widowhood effect on mortality. Nevertheless, long
      after spousal death, men suffer from a decline in the quality of informal care,
      coordination between formal and informal care, and the ability to advocate and
      communicate informal medical settings. These findings illustrate women's
      centrality in the household production of health and identify important points of
      intervention in optimizing men's adjustment to widowhood.

PMID- 19771946
TI  - Drawing statistical inferences from historical census data, 1850-1950.
AB  - Virtually all quantitative microdata used by social scientists derive from
      samples that incorporate clustering, stratification, and weighting adjustments
      (Kish 1965, 1992). Such data can yield standard error estimates that differ
      dramatically from those derived from a simple random sample of the same size.
      Researchers using historical U.S. census microdata, however, usually apply
      methods designed for simple random samples. The resulting p values and confidence
      intervals could be inaccurate and could lead to erroneous research conclusions.
      Because U.S. census microdata samples are among the most widely used sources for
      social science and policy research, the need for reliable standard error
      estimation is critical. We evaluate the historical microdata samples of the
      Integrated Public Use Microdata Series (IPUMS) project from 1850 to 1950 in order
      to determine (1) the impact of sample design on standard error estimates, and (2)
      how to apply modern standard error estimation software to historical census
      samples. We exploit a unique new data source from the 1880 census to validate our
      methods for standard error estimation, and then we apply this approach to the
      1850-1870 and 1900-1950 decennial censuses. We conclude that Taylor series
      estimation can be used effectively with the historical decennial census microdata
      samples and should be applied in research analyses that have the potential for
      substantial clustering effects.

PMID- 19771949
TI  - What we mean by social determinants of health.
AB  - This article analyzes the changes in health conditions and quality of life in the
      populations of developed and developing countries over the past 30 years,
      resulting from neoliberal policies developed by many governments and promoted by
      the World Bank, International Monetary Fund, World Health Organization, and other
      international agencies. It challenges interpretations by the analysts of
      "globalization", including the common assumption that states are disappearing.
      The author shows that what has been happening is not a reduction of state
      interventions but a change in the nature and character of those interventions,
      resulting from major changes in class (and race and gender) power relations in
      each country, with establishment of an alliance between the dominant classes of
      developed and developing countries-a class alliance responsible for the promotion
      of its ideology, neoliberalism. This is the cause of the enormous health
      inequalities in the world today. The article concludes with a critical analysis
      of the WHO report on social determinants of health, applauding its analysis and
      many of its recommendations, but faulting it for ignoring the power relations
      that shape these social determinants. It is not inequalities that kill people, as
      the report states; it is those who are responsible for these inequalities that
      kill people.

PMID- 19771948
TI  - Change in disability-free life expectancy for Americans 70-years-old and older.
AB  - In this article, we examine changes in life expectancy free of disability using
      longitudinal data collected from 1984 through 2000 from two cohorts who composed
      the Longitudinal Studies of Aging I and II. Life expectancies with and without
      ADL and/or IADL disability are calculated using a Markov-based multistate life
      table approach. At age 70, disability-free life expectancy increased over a 10
      year period by 0.6 of a year in the later cohort, which was the same as the
      increase in total life expectancy, both increases marginally statistically
      significant. The average length of expected life with IADL and ADL disability did
      not change. Changes in disability-free life expectancy resulted from decreases in
      disability incidence and increases in the incidence of recovery from disability
      across the two survey cohorts. Age-specific mortality among the ADL disabled
      declined significantly in the later cohort after age 80. Mortality for the IADL
      disabled and the nondisabled did not change significantly. Those with ADL
      disability at age 70 experienced substantial increases in both total life
      expectancy and disability-free life expectancy. These results indicate the
      importance of efforts both to prevent and delay disability and to promote
      recovery from disability for increasing life expectancy without disability.
      Results also indicate that while reductions in incidence and increases in
      recovery work to decrease population prevalence of disability, declining
      mortality among the disabled has been a force toward increasing disability
      prevalence.

PMID- 19771950
TI  - The U.S. employment effects of military and domestic spending priorities.
AB  - This study focuses on the employment effects of military spending versus
      alternative domestic spending priorities. The authors begin by introducing the
      basic input-output modeling technique for considering issues such as these in a
      systematic way. They then present some simple alternative spending scenarios
      namely, devoting $1 billion to the military versus the same amount of money spent
      for five alternatives: tax cuts that produce increased levels of personal
      consumption; health care; education; mass transit; and construction targeted at
      home weatherization and infrastructure repair. The first conclusion in assessing
      such relative employment effects is straightforward: $1 billion spent on personal
      consumption, health care, education, mass transit, and construction for home
      weatherization/infrastructure will all create more jobs in the U.S. economy than
      would the same $1 billion spent on the military. The authors then examine the pay
      level of jobs created through these alternative spending priorities and assess
      the overall welfare effects of the alternative employment outcomes. Combining
      these alternative domestic spending categories in an effective way can also
      generate a higher level of compensation for working people in the United States
      and a better average quality ofjobs.

PMID- 19771951
TI  - Rapid large-scale privatization and death rates in ex-communist countries: an
      analysis of stress-related and health system mechanisms.
AB  - During the transition to capitalism, the postcommunist countries have experienced
      devastating rises in mortality, although there has been considerable variation
      within and between countries and regions. Much of this population-level variation
      remains unexplained, but alcohol and psychological stress are found to be major
      proximal causes of rising mortality rates. The authors show that implementation
      of neoliberal-inspired rapid, large-scale privatization programs ("mass
      privatization") was associated with significant declines in life expectancy, as
      well as with greater alcohol-related deaths, heart disease, and suicide rates.
      The authors interpret these findings as evidence that rapid organizational reform
      created excess psychosocial stress, which, consistent with the public health
      literature, increases risk of death at the individual level. However, they also
      find that rapid privatization modestly contributed to a decline in health care
      resources, such as the number of physicians, dentists, and hospital beds per
      capita, although there is weak evidence that these reductions in health system
      capacity explain substantial differences in mortality at the country level.

PMID- 19771952
TI  - Experiences from the Swedish determinants-based public health policy.
AB  - A comprehensive Swedish public health policy was adopted by the Swedish
      Parliament, the Riksdag, in April 2003. It pushes health up on the political
      agenda and affords equity in health high priority. The first phase of
      implementation of the policy, 2003-5, is described in the 2005 Public Health
      Policy Report published by the Swedish National Institute of Public Health
      (SNIPH). For the purpose of investigating the implementation, SNIPH has monitored
      the development of 42 determinants and used reports from 22 central agencies and
      eight county administrative boards together with interviews with all Sweden's
      county councils (21) and a questionnaire sent out to all municipalities (290).
      The experiences from the implementation of the policy are that: the determinants
      approach-focusing on structural factors in society, people's living conditions,
      and health behaviors that affect health-is in general well understood and
      emphasizes the role of other sectors in public health; the use of indicators to
      follow up exposures to determinants is of key importance; the support to actors
      outside the health service is needed to identify their public health role; a
      continuous steering from the government and other political bodies is of vital
      importance; public health promotion on the regional level needs a higher level of
      coordination; municipalities need more skills development. Sweden has a new
      government that was elected in September 2006; the new government has retracted
      the former government's public health policy communication submitted to the
      Riksdag in the spring of 2006, but does not intend to change the public health
      policy.

PMID- 19771953
TI  - Policies to tackle health inequalities in Norway: from laggard to pioneer?
AB  - This study addresses recent public health policies in Norway, asking how policies
      on health inequalities have developed over the past 20 years. The authors focus
      on how the problem has been defined, what goals have been set, and what means
      have been put forward to achieve them. The data consist of official documents and
      interviews of key actors in research and the health bureaucracy. The results
      indicate that the theme of health inequalities has developed from a non-topic to
      a high-priority topic in Norway's public health policy. This change has been
      accompanied by formulation of clear goals and an overarching and long-term
      strategy, including concrete means to reduce health inequalities. Over the past
      five years, the problem definition has changed from one of individualization with
      a focus on health behaviors to a structural understanding that emphasizes the
      problem of the gradient and social determinants of health. Norway is on the move
      from a state of political indifference toward action in developing comprehensive,
      coordinating policy.

PMID- 19771954
TI  - Income and health in Canada: Canadian researchers' conceptualizations make policy
      change unlikely.
AB  - The research reported here identified and evaluated gaps in Canadian knowledge
      and research activity concerning the role of income and its distribution in
      influencing health outcomes. The study consisted of an analysis of 241 recent
      Canadian research studies, the components of which were compared with 40 U.K. and
      40 Finnish studies that applied advanced conceptualizations of the income-health
      relationship. Canadian health researchers rarely made explicit their
      conceptualizations of how income was approached in their studies, and most did
      not identify the structural mechanisms that mediate the income-health
      relationship. There were few Canadian longitudinal studies capable of
      illuminating the role of income in health across the lifespan. Many Canadian
      studies identified pathways by which income might influence health, but these
      conceptualizations were underdeveloped. Canadian researchers need to strengthen
      their conceptualizations of how income and its distribution affect health. While
      empirical research is only one contributor to positive policy change, the narrow
      nature of Canadian work will do little to influence this process.
      Interdisciplinary work on the political, economic, and social forces that
      contribute to income inequalities has the potential, when combined with political
      and social action, to facilitate public policy in support of health.

PMID- 19771955
TI  - Health care use and the Canadian immigrant population.
AB  - Set within the "determinants of health" framework and drawing on Statistics
      Canada's longitudinal National Population Health Survey, this article explores
      health care utilization by Canada's immigrant population. Given the observed
      "healthy immigrant effect", whereby the health status of immigrants at the time
      of arrival is high but subsequently declines and converges toward that of the
      native-born population, does the incidence of use of health care facilities
      reflect greater need for care? Similarly, does the use of health care facilities
      by the native- and the foreign-born differ, and if so, are these differences
      explained primarily by socioeconomic, sociodemographic, or lifestyle factors,
      which may point to problems in the Canadian health care system? This study
      identifies trends in the incidence of physician and hospital use, the factors
      that contribute to health care use, and differences in health care use between
      the native- and foreign-born.

PMID- 19771956
TI  - Prospects for a genuine revival of primary health care--through the visible hand
      of social justice rather than the invisible hand of the market: part I.
AB  - In a two-part article (the first part in this Journal issue), the author explores
      the prospects for a genuine revival of the social justice project of "Health for
      All by the Year 2000", launched by the WHO and UNICEF in 1978 at Alma-Ata in the
      former Soviet Union, with reference (in Part I) to the World Health Report 2008,
      Primary Health Care: Now More than Ever, and the report of the WHO Commission on
      Social Determinants of Health, also published in 2008; and (in Part II) to Global
      Health Watch 2: An Alternative World Health Report and the perspectives of anti
      capitalist, real socialist, environmental, and people's movements for economic
      and social justice. The reports are reviewed in terms of the original values and
      principles of Alma-Ata (social justice and human rights) and the structural
      foundations of the primary health care (PHC) project (a new international
      economic order and emancipatory development of decolonized countries). A genuine
      revival of the PHC project and of Health for All, which is its implicit
      objective, will not be possible unless the multiple crises that we are
      confronting today-in energy, water, food, finance, the environment, science,
      information, and democracy-are recognized as capitalist crises and addressed in
      these terms. In short, the invisible hand of the market must be replaced by the
      visible hand of social justice.

PMID- 19771957
TI  - The making of a Chinese head of the WHO: a study of the media discourse on
      Margaret Chan's contest for the WHO director-generalship and its implications for
      the collective memory of SARS.
AB  - In 2003, Margaret Chan Fung Fu-chun, former Director of Health of the Hong Kong
      government, was criticized for her unsatisfactory performance in handling the
      SARS outbreak. But three years later, she was celebrated for her success in the
      contest for the WHO director-generalship. How was she transformed from an
      incompetent official into an "honor winner" for China and Hong Kong? In what
      context was this made possible? How was the collective memory about Chan recalled
      and reconstructed? This article tackles these questions by reviewing relevant
      reportage and commentary in major local (Hong Kong), national (China), and
      international media. It maps the political context of the media discourse and
      explores the construction of a collective past to foster national cohesion in
      postcolonial Hong Kong.

PMID- 19771958
TI  - ARFI ultrasound for in vivo hemostasis assessment postcardiac catheterization,
      part I: preclinical studies.
AB  - The world wide prevalence of cardiovascular disease leads to over seven million
      annual percutaneous coronary catheterization procedures, the majority of which
      exploit femoral artery access. Femoral puncture sites ('arteriotomies') can be
      associated with severe vessel complications after sheath removal if hemostasis is
      not properly achieved. Hemostasis onset is routinely determined by examination
      for bleeding at the skin puncture; however, clotting along the puncture path can
      obscure subcutaneous bleeding, and therefore hemostasis is blindly assessed. We
      hypothesize that hemostasis assessment can be un-blinded by Acoustic Radiation
      Force Impulse (ARFI) ultrasound. In this first of a two-part series, we present
      in vivo ARFI hemostasis imaging data obtained in relevant canine models of
      femoral artery puncture. Above arteriotomies, ARFI-induced displacements were
      large (3.5 to >5.0 microm) relative to surrounding soft tissue soon after needle
      removal, which was consistent with our expectation for pooled extravasated blood.
      ARFI-induced displacements above arteriotomies decreased in magnitude (to
      approximately 2 microm) some time after needle removal and suggested the onset of
      hemostasis. This preclinical investigation served as proof of concept and
      justification for a pilot human study, which is presented in part two of this
      series.

PMID- 19771959
TI  - ARFI ultrasound for in vivo hemostasis assessment postcardiac catheterization,
      part II: pilot clinical results.
AB  - In this second of a two part series, we present pilot clinical data demonstrating
      Acoustic Radiation Force Impulse (ARFI) ultrasound for monitoring the onset of
      subcutaneous hemostasis at femoral artery puncture sites (arteriotomies), in
      vivo. We conducted a randomized, reader-blinded investigation of 20 patient
      volunteers who underwent diagnostic percutaneous coronary catheterization. After
      sheath removal (6 French), patients were randomized to treatment with either
      standard of care manual compression alone or, to expedite hemostasis, manual
      compression augmented with a p-GlcNAc fiber-based hemostatic dressing (Marine
      Polymer Technologies, Danvers MA). Concurrent with manual compression, serial
      ARFI imaging began at the time of sheath removal and continued every minute for
      15 min. Serial data sets were processed with custom software to (1) estimate the
      time of hemostasis onset, and (2) render hybrid ARFI/B-Mode images to highlight
      displacements considered to correspond to extravasted blood. Images were read by
      an observer blinded to the treatment groups. Average estimated times to
      hemostasis in patient volunteers treated with manual compression alone (n = 10)
      and manual compression augmented by hemostatic dressing (n = 9) were,
      respectively, 13.00 +/- 1.56 and 9.44 +/- 3.09 min, which are statistically
      significantly different (p = 0.0065, Wilcoxon two-sample test). Example images
      are shown for three selected patient volunteers. These pilot data suggest that
      ARFI ultrasound is relevant to monitoring subcutaneous bleeding from femoral
      arteriotomies clinically and that time to hemostasis was significantly reduced by
      use of the hemostatic dressing.

PMID- 19771960
TI  - On the feasibility of imaging peripheral nerves using acoustic radiation force
      impulse imaging.
AB  - Regional anesthesia is preferred over general anesthesia for many surgical
      procedures; however, challenges associated with poor image guidance limit its
      widespread acceptance as a viable alternative. In B-mode ultrasound images, the
      current standard for guidance, nerves can be difficult to visualize due to their
      similar acoustic impedance with surrounding tissues and needles must be aligned
      within the imaging plane at limited angles of approach that can impede successful
      peripheral nerve anesthesia. These challenges lead to inadequate regional
      anesthesia, necessitating intraoperative interventions, and can cause
      complications, including hemorrhage, intraneural injections and even nerve
      paralysis. ARFI imaging utilizes acoustic radiation force to generate images that
      portray relative tissue stiffness differences. Peripheral nerves are typically
      surrounded by many different tissue types (e.g., muscle, fat and fascia) that
      provide a mechanical basis for improved image contrast using ARFI imaging over
      conventional B-mode images. ARFI images of peripheral nerves and needles have
      been generated in cadaveric specimens and in humans in vivo. Contrast
      improvements of >600% have been achieved for distal sciatic nerve structures. The
      brachial plexus has been visualized with improved contrast over B-mode images in
      vivo during saline injection and ARFI images can delineate nerve bundle
      substructures to aid injection guidance. Physiologic motion during ARFI imaging
      of nerves near arterial structures has been successfully suppressed using ECG
      triggered image acquisition and motion filters. This work demonstrates the
      feasibility of using ARFI imaging to improve the visualization of peripheral
      nerves during regional anesthesia procedures.

PMID- 19771961
TI  - Novel acoustic radiation force impulse imaging methods for visualization of
      rapidly moving tissue.
AB  - Acoustic radiation force impulse (ARFI) imaging has been demonstrated to be
      capable of visualizing changes in local myocardial stiffness through a normal
      cardiac cycle. As a beating heart involves rapidly-moving tissue with cyclically
      varying myocardial stiffness, it is desirable to form images with high frame
      rates and minimize susceptibility to motion artifacts. Three novel ARFI imaging
      methods, pre-excitation displacement estimation, parallel-transmit excitation and
      parallel-transmit tracking, were implemented. Along with parallel-receive, ECG
      gating and multiplexed imaging, these new techniques were used to form high
      quality, high-resolution epicardial ARFI images. Three-line M-mode, extended ECG
      gated three-line M-mode and ECG-gated two-dimensional ARFI imaging sequences were
      developed to address specific challenges related to cardiac imaging. In vivo
      epicardial ARFI images of an ovine heart were formed using these sequences and
      the quality and utility of the resultant ARFI-induced displacement curves were
      evaluated. The ARFI-induced displacement curves demonstrate the potential for
      ARFI imaging to provide new and unique information into myocardial stiffness with
      high temporal and spatial resolution.

PMID- 19771963
TI  - The business side of dentistry.

PMID- 19771962
TI  - In vivo cardiac, acoustic-radiation-force-driven, shear wave velocimetry.
AB  - Shear wave elasticity imaging (SWEI) was employed to track acoustic radiation
      force impulse (ARFI)-induced shear waves in the mid-myocardium of the left
      ventricular free wall (LVFW) of a beating canine heart. Shear waves were
      generated and tracked with a linear ultrasound transducer that was placed
      directly on the exposed epicardium. Acquisition was ECG-gated and coincided with
      the mid-diastolic portion of the cardiac cycle. Axial displacement profiles
      consistent with shear wave propagation were clearly evident in all SWEI
      acquisitions (i.e., those including an ARFI excitation); displacement data from
      control cases (i.e., sequences lacking an ARFI excitation) offered no evidence of
      shear wave propagation and yielded a peak absolute mean displacement below 0.31
      microm after motion filtering. Shear wave velocity estimates ranged from 0.82 to
      2.65 m/s and were stable across multiple heartbeats for the same interrogation
      region, with coefficients of variation less than 19% for all matched
      acquisitions. Variations in velocity estimates suggest a spatial dependence of
      shear wave velocity through the mid-myocardium of the LVFW, with velocity
      estimates changing, in limited cases, through depth and lateral position.

PMID- 19771964
TI  - Using a nanohybrid composite with ceramic-like properties.
AB  - IPS Empress Direct is a nanohybrid composite exhibiting remarkable handling
      properties that combines the aesthetics of ceramic with the chairside direct
      placement convenience of a composite. Suitable for placing both anterior and
      posterior restorations, IPS Empress Direct enhances the restorative process,
      demonstrates high stability, and exhibits shade fidelity and enhanced polishing
      properties (Figure 6). Its physical properties are specially designed for
      simplified application. Low sensitivity to light ensures ample, pressure-free
      working time for designing restorations.

PMID- 19771965
TI  - Upgrading to digital radiography to boost productivity.

PMID- 19771966
TI  - Using Triodent V3 rings and V3 matrices to control the contact points for direct
      posterior composites.

PMID- 19771968
TI  - In the spotlight: three of the hottest topics in dentistry! Interview by Damon
      Adams.

PMID- 19771967
TI  - Tooth stabilization improves periodontal prognosis: a case report.

PMID- 19771969
TI  - Photography: an integral component of oral cancer screening.

PMID- 19771970
TI  - Accurate placement of implant abutments using acrylic resin jig.

PMID- 19771971
TI  - Implant placement in infected sites.

PMID- 19771972
TI  - Discussion of a complex endodontic case: when to refer.
AB  - A clinical case has been presented which discusses the clinical pre- and post-op
      assessment of a challenging clinical case. Emphasis has been placed on risk
      assessment as well as prevention of iatrogenic events by achievement and
      maintenance of apical patency as well as attainment of an ideal master apical
      taper and diameter.

PMID- 19771973
TI  - Endoimplantology: part 2, surgical classifications.
AB  - The morphic classification developed is a silver lining enabling projection, as
      well as retraction, for complex surgical approaches where ultimate decisions may
      have to be taken extemporaneously as the surgical case develops. From both a
      consent form and clinical standpoint, this approach brings clarity to the patient
      avoiding surprises and disappointment. It also guides the practitioner whose best
      clinician intention may not alway materialize and guaranty the best and most
      reasonable possible achievement.

PMID- 19771974
TI  - Engineering the implant-retained overdenture.

PMID- 19771975
TI  - Excellence and predictability: not an accident!

PMID- 19771976
TI  - Smart software to grow your dental practice.

PMID- 19771977
TI  - Immediate dentin sealing technique.

PMID- 19771978
TI  - Social networking for dentists--made easy!
AB  - Professional social networks are making it easier for dentists to connect,
      collaborate, and share. They are making it easier for associations to put their
      message in front of dentists on a social network for dentistry-exclusively about
      dentistry. For those dentists looking to manage a study club or a dental
      association, the tools on NewDocs make it not only easy but fun for all of its
      members. Start today, and find out why professional social networking is changing
      our professional world!

PMID- 19771980
TI  - Design, build, or makeover your office in three simple steps.

PMID- 19771979
TI  - Moving up with digital impression technology.

PMID- 19771981
TI  - A new National Women's Health Policy: legal, ethical and policy initiatives to
      support women's health.
AB  - In 1989 the first National Women's Health Policy was launched in Australia. Now,
      20 years later, the Federal Government has announced plans for the development of
      a new National Women's Health Policy to address the health needs of Australian
      women. The Policy will be based on five principles: gender equity; health equity
      between women; a focus on prevention; an evidence base for interventions; and a
      life course approach. This editorial examines the role for law in the development
      of a new National Women's Health Policy. It considers the relevance of regulatory
      frameworks for health research in supporting an evidence base for health
      interventions and analyses the requirement in the National Health and Medical
      Research Council's National Statement on Ethical Conduct in Human Research for
      "fair inclusion" of research participants. The editorial argues for a holistic
      approach to women's health that includes regulatory frameworks for research,
      identification of funding priorities for research, and the need for a dedicated
      government department or agency to promote women's health.

PMID- 19771982
TI  - Mental health laws for those "compliant" with treatment.
AB  - The focus of current mental health laws is on the involuntary detention and
      treatment of those with low-prevalence, serious mental illnesses such as
      schizophrenia and bipolar disorder. However, an international trend is developing
      towards using mental health laws to safeguard the rights of patients who lack the
      capacity to consent to treatment but who are not objecting to it. This column
      analyses the legislative response in England and Wales to a decision by the
      European Court of Human Rights indicating that there should be legislative
      procedures for those lacking capacity to consent, but who are "compliant" with
      treatment.

PMID- 19771983
TI  - Forensic experts and miscarriages of justice: the inquiry into pediatric forensic
      pathology in Ontario.
AB  - The care and protection of children in our community is usually given one of the
      highest priorities by governments and service providers. Similarly, we respond
      severely to those proven to have abused or caused deliberate harm to children.
      Acceptance of these high standards is predicated on our ability to correctly
      identify and appropriately investigate alleged crimes against children. When
      concerns regarding expertise in the correct detection of child abuse arise, they
      can significantly impair the justice system and lead to considerable social harm,
      as evidenced by the results of the inquiry into paediatric forensic pathology in
      Ontario. The inquiry found that the failures of the paediatric forensic pathology
      service in that Province did not occur in isolation but were allowed to be
      perpetuated over time by the action and inaction of a range of individuals and
      agencies. Deficiencies in governance, accreditation, training, supervision, audit
      and review were all highlighted in the findings of the commission. These are
      relevant not only to Ontario but to many jurisdictions where forensic medical and
      legal services continue to struggle with the special scientific and legal issues
      that are raised by child abuse.

PMID- 19771984
TI  - Full steam ahead on the SS "external regulator"? Mandatory reporting,
      professional independence, self-regulation and patient harm.
AB  - Mandatory reporting by medical practitioners of their colleagues who demonstrate
      poor clinical performance, are intoxicated while working or have sexual relations
      with patients, has been recently legislated for in New South Wales, and is likely
      to become law in Queensland. Somewhat similar legislation was introduced in New
      Zealand in relation to most health practitioners, but resistance, particularly
      from the New Zealand Medical Association, resulted in discretionary, as opposed
      to mandatory, reporting. The National Registration and Accreditation Scheme for
      the Health Professions in Australia is also canvassing mandatory reporting for 10
      major health profession registrants, as part of its processes for dealing with
      performance, health and conduct matters. Mandatory reporting is an important
      incursion on the self-regulation functions and privileges of the health
      professions. The medical profession, in particular, has resisted mandatory
      reporting provisions, but appears not to discern that its allegiance to a model
      of traditional rather than transparent self-regulation may be self-defeating.

PMID- 19771986
TI  - Variables in health care policy-making: resolving a quandary?
AB  - Contemporary debate on health care resource management is tied to a central moral
      issue: how to achieve an optimum level of reasonable or appropriate treatment
      based on the medical condition of each patient. Failure to tackle and resolve
      this issue in a confident and forthright manner ensures that the present approach
      to health care decision-making will continue in a state of indecisiveness if not,
      indeed, lethargy. Undergirding this moral issue is the foundational economic
      dilemma of controlling costs while limiting access to health care resources.
      Crafting a just solution to an equitable distribution of finite health care
      resources is, indeed, a quandary, if not almost an impossibility. What this
      article seeks to do, nonetheless, is to undertake an examination of the
      principles, socio-economic values and public policies needed to formulate health
      care compromises necessary to achieve greater stability in the normative decision
      making process. In turn, this will ensure, ideally, a level of distributive
      justice in the total allocative process.

PMID- 19771985
TI  - Australian professional practice bodies and the tort of negligent investigation.
AB  - The New South Wales Supreme Court has examined the statutory and common law
      duties of the New South Wales Health Care Complaints Commission and the New South
      Wales Medical Board in the recent case of Attorney General (NSW) v Bar-Mordecai
      [2008] NSWSC 774. The judgment establishes that a professional practice body
      investigating the alleged misconduct of a doctor will rarely be liable under
      Australian statutory or common law duties to compensate that doctor for harm
      arising as a result of negligent investigatory practices. In particular, it
      establishes that such a body owes no duty to take reasonable care to avoid
      psychiatric injury to a medical practitioner against whom a complaint has been
      lodged and whom it is investigating. It is argued that the differing approaches
      to the tort of negligent investigation in Canada and Australia stem from
      differences not only in policy values but in the legal frameworks used in each
      jurisdiction to determine the existence of duties of care at common law.

PMID- 19771987
TI  - Cross-border issues in the development of medical tourism in Malaysia: legal
      challenges and opportunities.
AB  - Strategically located at the crossroads of Asia, Malaysia has become one of the
      key players in the fast-growing and lucrative market for health care services in
      Asia. Medical travel across international boundaries has been made possible
      through affordable airfares and the favourable exchange rates of the Malaysian
      ringgit has contributed to the rise of the "medical tourism phenomenon" where
      medical travel is combined with visiting popular tourist destinations in
      Malaysia. Further, competitive medical fees and modern medical facilities have
      also made Malaysia a popular destination for medical tourists. Nevertheless, the
      increased number of foreign patients has opened up possibilities of Malaysian
      health care providers being subjected to malpractice claims and triggering a
      myriad of cross-border legal issues. Presently, there is no internationally
      accepted legal framework to regulate medical tourism and issues of legal redress
      in relation to unsatisfactory provision of treatment across international
      boundaries. The economic benefits of medical tourism must be based upon a solid
      legal regulatory framework and strong ethical standards as well as upon high
      quality medical and health care services. It is therefore important to assess the
      existing legal framework affecting the development of medical tourism in Malaysia
      in order to explore the gaps, deficiencies and possibilities for legal and
      regulatory reform.

PMID- 19771988
TI  - Using mediation in situations of withholding or withdrawing life-sustaining
      treatment: a New South Wales perspective.
AB  - Whether to withhold or withdraw life-sustaining treatment from a person lacking
      competency is an extremely difficult decision for both the person's family and
      for a medical practitioner. Family members face being part of a decision which
      may lead to the death of a loved one. Practitioners face considerable pressure to
      make the right care recommendation and to protect their patient's best interests.
      This creates a charged emotional environment, where clear and unambiguous
      communication between all involved is essential. Mediation may be under-utilised
      in these situations, offering, as it does, the prospect of improved decision
      making processes and outcomes. However, certain aspects of the American
      "bioethics mediation" model would not work well in New South Wales or elsewhere
      in Australia. Instead, a more "classical" mediation model, utilising the New
      South Wales Health Conciliation Registry in a new way, is preferable.

PMID- 19771989
TI  - Registration of clinical trials: challenges for global regulation.
AB  - In 2004 the International Committee of Medical Journal Editors (ICMJE) issued a
      statement indicating that from 1 July 2005 registration in a publicly accessible
      trials registry would be a condition of publication in an ICMJE member journal.
      The World Health Organisation is coordinating the International Clinical Trials
      Registry Platform (ICTRP) as a means of providing a standardised framework for
      registration. This article considers the practical challenges and opportunities
      that arise from these developments and considers the relevance of trial
      registration for women and minorities and for developing countries.

PMID- 19771990
TI  - The NHS Redress Act 2006 (UK): background and analysis.
AB  - The NHS Redress Act 2006 (UK) is an example of a legislated compensation scheme
      for adverse health care incidents that aims to supplement the tort-based system
      of compensation, without going all the way to adopting a no-fault compensation
      system. It proposes an administrative method of providing speedier and more
      efficient and responsive remedies to adverse health care incidents than
      traditional legal proceedings. This article examines the detail of the United
      Kingdom policy arguments both prior to and since the passage of the legislation,
      as well as providing a detailed analysis of the original Bill, the parliamentary
      debates and the subsequent Act.

PMID- 19771991
TI  - Medical-legal partnerships: a new beginning to help Australian children in need.
AB  - Drawing on the strengths of both the medical and legal professions can reduce
      health inequities and preventable illnesses in children from vulnerable families.
      In response to frequent reports on high-risk injuries and illnesses in children
      from disadvantaged and isolated communities, the possibility of a
      multidisciplinary partnership, currently used throughout the United States of
      America, is explored. Given the limitations of each discipline on their own, the
      concept of medical-legal partnerships presents an innovative and strategic
      approach towards caring for Australia's most vulnerable. The development of this
      partnership will encourage and empower such groups to access fundamental legal
      and medical resources. The benefits and obstacles of such a partnership, together
      with social, economic and health data, are examined to reveal the urgent need to
      adopt a more meaningful approach towards family and paediatric health care.
      Finally, some of Australia's existing laws and practices are considered and brief
      recommendations are provided to initiate a proactive solution for the future.

PMID- 19771992
TI  - An empirical reappraisal of public trust in biobanking research: rethinking
      restrictive consent requirements.
AB  - Collections of human tissue removed from patients in the course of medical
      diagnosis or therapy are believed to be an increasingly important resource for
      medical research (biobank research). As a result of a number of tissue-related
      "scandals" and increasing concern about ownership and privacy, the requirements
      to obtain consent from tissue donors are becoming increasingly stringent. The
      authors' data show that members of the general public perceive academic biobank
      researchers and their institutions to be highly trustworthy and do not see the
      need for recurrent, project-specific consent. They argue, on the basis of their
      empirical findings, that we should question the trend, at least in some settings,
      toward ever more stringent consent requirements for the use of tissue in
      research. They argue that this approach, while perhaps counterintuitive in the
      current regulatory environment, can be both ethically and legally sound so long
      as channels of communication are maintained and third-party relationships are
      tightly controlled.

PMID- 19771993
TI  - The role of the expert witness in the adversarial legal system.
AB  - So often we hear the legal profession berate expert witnesses as "hired guns"
      whose bias is for sale. While this may be relevant to a small minority of
      "experts", the majority do their job with integrity and in an ethical fashion. An
      advocate for a proposition will not call a witness to support a claim if it is
      clear that the witness holds an opposing view. It follows that the bias emanates
      from the lawyer, not the witness. A witness without a formed view cannot truly
      claim to be an expert, as the expert should have sufficient knowledge to form an
      opinion. Once that opinion has been expressed and justified, the lawyer will
      select the most persuasive and cogently constructed opinion with which to
      convince the court. The expert witness must commence the assessment without bias
      or favour; must collect her or his history and examination of the relevant
      material; evaluate all the facts and evidence provided for scrutiny; seek
      additional material where there appears to be a deficiency; and draw on all of
      these data to formulate an opinion in response to questions posed by the
      instructing lawyer. The expert need not support or refute the stance proposed by
      the lawyer but the lawyer will only use those opinions favourable to the lawyer's
      case and hold the remainder as privileged where even that option prevails. It
      follows that the role of the expert is to provide a well-prepared analysis; it is
      the lawyer who is paid to be biased.

PMID- 19771994
TI  - Assessing stakeholder needs for the introduction of assisted reproductive
      technology legislation.
AB  - Assisted reproductive technology (ART) legislation in Victoria, Australia, is
      currently under review. Due to the complex nature of ART legislation, careful
      planning is required to ensure key stakeholders understand the revisions to ART
      legislation in Victoria and that they have sufficient time to consider and
      implement necessary changes. Focus groups were conducted to assess the
      communication and education needs of the staff of places licensed to provide ART
      treatment in Victoria related to the introduction of new ART legislation and to
      inform the development of a supporting implementation strategy to meet those
      needs. Stakeholder needs were found to vary widely according to geographic
      location, size and structure of organisations. A range of education and
      communication strategies must be considered. A multi-pronged communication and
      education strategy is required to ensure that ART legislation is introduced
      effectively and that the needs of stakeholders are met.

PMID- 19771995
TI  - Relating to patients.

PMID- 19771996
TI  - Is the antenatal prediction of fetal macrosomia worthwhile?

PMID- 19771997
TI  - The importance of oral health for the systemic well being of an ageing
      population.

PMID- 19771998
TI  - Male fertility in cystic fibrosis.
AB  - Infertility rates among males with cystic fibrosis (CF) approximate 97%. No
      information is currently available within Ireland determining an understanding of
      fertility issues and the best methods of information provision to this
      specialized group. This study aimed to determine understanding and preferred
      approaches to information provision on fertility issues to Irish CF males. A
      Descriptive Study utilizing prospective coded questionnaires was mailed to a male
      CF cohort (n=50). Sections included demographics, fertility knowledge &
      investigation. Response rate was 16/50 (32%). All were aware that CF affected
      their fertility. More than two-thirds (n=11) were able to provide explanations
      whilst only one-third (n=5) provided the correct explanation. Significant numbers
      stated thoughts of marriage and a future family. Half have discussed fertility
      with a healthcare professional (HCP). Mean age of discussion was 21.9 years. One
      third preferred an earlier discussion. The commonest first source for information
      was written material which was also the preferred source. Three-quarters
      requested further information preferring again, written material. Significant
      gaps in sex education of Irish CF males exist. Discussion should be initiated by
      HCPs and centre-directed written material devised to address deficiencies.

PMID- 19771999
TI  - Is the contribution of alcohol to fatal traumatic brain injuries being
      underestimated in the acute hospital setting?
AB  - Alcohol consumption in Ireland has nearly doubled during the period 1989-2001. To
      evaluate the relationship of alcohol to fatal head injuries in the acute hospital
      setting we created a data base of all fatal traumatic brain injuries in the
      Department of Neuropathology at Beaumont Hospital over a ten year period (1997
      2006 inclusive). 498 cases were identified (351 males: 147 females). Fatalities
      were highest in males aged 19-25 years (N=101) and 51-70 years (N=109). Falls
      (N=210) and road traffic accidents (N=183) were the commonest modes of
      presentation. 36/210 (17%) falls had positive blood alcohol testing, 9/210 (4.3%)
      had documentation of alcohol in notes but no testing, 35/210 (16.7%) tested
      negative for alcohol and 130/210 (61.9%) were not tested. The RTA group (N=183)
      comprised drivers (n=79), passengers (n=47) and pedestrians (n=57). 65/79 (82.2%)
      of drivers were males aged 19-25 years. Blood alcohol was only available in 27/79
      (34.1%) drivers and was positive in 13/27 (48.1%). 14/75 (18.7%) pedestrians were
      tested for alcohol, 4/14 (28.6%) were positive. Overall 142/183 (77.6%) of the
      RTA group were not tested. The contribution of alcohol to fatal traumatic brain
      injuries is probably being underestimated due to omission of blood alcohol
      concentration testing on admission to hospital. Absence of national guidelines on
      blood alcohol testing in the emergency department compounds the problem.

PMID- 19772001
TI  - Percutaneous vertebroplasty in osteoporosis, myeloma and Langerhans' cell
      histiocytosis.
AB  - This review aims to assess the effectiveness of percutaneous vertebroplasty as a
      treatment for the severe refractory pain associated with vertebral fracture, in a
      group of patients with fractures secondary to either osteoporotic or neoplastic
      disease. A retrospective review of 20 patients treated with percutaneous
      vertebroplasty in Cork University Hospital up until March 2007 was carried out
      and a questionnaire was prepared and distributed. Prior to vertebroplasty,
      patients had been symptomatic with severe pain for a mean of 20.9 weeks. Of those
      thirteen whom replied to a postal questionnaire, 12 (92.3%) reported pain relief
      and this improvement occurred within 7 days in 9 (81.8%). This was associated
      with decreased analgesic requirements, as determined on chart review. Prior to
      the procedure only 5 (38.4%) were independently mobile and this figure rose to 10
      (76.9%) afterwards, occurring within one week in the majority. Subjective
      outcomes were better in the group of patients with neoplasm-induced fractures.

PMID- 19772000
TI  - Shared consultant physician posts.
AB  - Our aim was to assess the acceptability and cost-efficiency of shared consultancy
      posts. Two consultant physicians worked alternate fortnights for a period of
      twelve months. Questionnaires were distributed to general practitioners, nurses,
      consultants and junior doctors affected by the arrangement. Patients or their
      next of kin were contacted by telephone. 1/17 of consultants described the
      experience as negative. 14/19 junior doctors reported a positive experience. 11
      felt that training had been improved while 2 felt that it had been adversely
      affected. 17/17 GPs were satisfied with the arrangement. 1/86 nurses surveyed
      reported a negative experience. 1/48 patients were unhappy with the arrangement.
      An extra 2.2 (p<0.001) patients were seen per clinic. Length of stay was
      shortened by 2.49 days (p<0.001). A saving of 69,212 was made due to decreased
      locum requirements. We present data suggesting structured shared consultancy
      posts can be broadly acceptable and cost efficient in Ireland.

PMID- 19772002
TI  - Managing ureteric colic in a smaller hospital without urological support.
AB  - No official guidelines exist on managing ureteric colic in small hospitals
      without urological support. We reviewed the logistics of managing this condition
      by examining all cases of ureteric colic over two years. Seventy nine of 118
      cases had hydronephrosis; a criteria for urology referral. Thirty nine patients
      passed their stone spontaneously but 40 of these cases could not and required
      transfer. Twenty two (55%) patients were transferred (mean time to transfer: 3.29
      days). The other 18 (45%) were discharged to await a urology outpatients clinic
      (mean time to discharge: 3.00 days). Patients that passed their stone
      spontaneously generally had stones under 5mm (mean stay: 2.09 days). We would
      recommend that patients with stones over 5mm or with hydronephrosis be referred
      immediately to prevent urological sepsis and or renal impairment.

PMID- 19772003
TI  - A comparison of CO2 laser versus traditional stapedectomy outcomes.
AB  - The aim of this study was to audit the introduction of the use of the CO2 laser
      into our department and to compare hearing outcomes and complication rates in
      patients who underwent either laser or mechanical stapedectomy. We found that the
      use of laser is at least as safe as the traditional approach with regards the
      rate of post-operative complications. One patient in the laser group suffered
      prolonged post-operative tinnitus, whilst one patient in the traditional group
      suffered prolonged post-operative vertigo. There was no evidence, however, of
      improved Air-Bone Gap closure compared to the traditional approach (Pre- and Post
      Op Air Bone Gaps of 34 +/- 3 and 9 +/- 2 for laser stapedectomy versus 35 +/- 4
      and 13 +/- 2 for traditional stapedectomy (mean +/- SEM)). In summary, therefore,
      CO2 laser surgery for otosclerosis is a safe surgical procedure resulting in
      similar hearing outcomes to that obtained following mechanical stapes surgery.

PMID- 19772004
TI  - Being old in Ireland: a fit state?
AB  - This is a cross-sectional, interview-based study profiling the health-status,
      functional ability and patterns of service use of an age-stratified random sample
      of 766 people over 70. Of 495 respondents (response rate 64.4%), 65% (n=324)
      rated their health as good/very good/excellent, 36% (n=180) reported long-term
      illness, 17% (n=82) had a moderate/severe disability. Of those living alone,
      68.7% (n=125/182) were female, 39.6% (n=72/182) were over-80, 28.7% (n=51/178)
      had no fire alarm, 58.9 % (n=102/173) had no panic alarm. Of those who do not
      have a car, 66.3% (n=174/262) rely mainly on friends/family for transport. 40.7%
      (n=24/59) of respondents with moderate/severe disability reported no state
      provided home-help. Despite much good news, a substantial vulnerable minority of
      older people would benefit from additional support: rural transport schemes and
      smoke alarm schemes should be extended; a formal needs assessment of homecare
      needs of older people should be considered; numbers of community therapists and
      access to home-help should be increased.

PMID- 19772005
TI  - Internally-developed electronic reporting system for medication errors.
AB  - To date, no work has been published regarding internal electronic patient safety
      reporting systems in the Irish hospital setting and limited international data is
      available regarding the impact of such programmes. In this report we describe the
      successful design and implementation of an online medication error reporting
      system in a 1017-bed Irish teaching hospital. In-house development has resulted
      in a system tailored to the needs of the hospital, with the flexibility to adapt
      to the future demands of the medication safety programme. Its introduction has
      led to a positive impact on reporting rates and on data management and has
      facilitated the development of safety initiatives.

PMID- 19772006
TI  - Incidence of hip fractures in Dublin's north inner city.
AB  - Hip fractures are an important cause of morbidity and mortality in the elderly
      and represent an increasing burden on health service providers. There is
      significant regional and international variation in the incidence rates of such
      injuries, depending on age, sex and ethnic variations in populations. To date,
      there are no reported incidence rates for hip fractures in Ireland. Over a five
      year period, 717 low energy hip fractures were treated in the orthopaedic trauma
      unit of the Mater Misericordiae hospital. For this population, the female to male
      ratio was 3.3:1 (549 females and 166 males), the gender specific incidences were
      470 per 100,000 and 179 per 100,000 for females and males, respectively. The
      overall age standardized rate was 341 per 100,000. This study quantifies the
      burden of hip fracture on a local population. With this knowledge, health service
      providers should be able to allocate appropriate resources for these patients in
      terms of acute and step-down care facilities.

PMID- 19772007
TI  - The uptake and use of the Monospot test in patients with tonsillitis.
AB  - The objective of the study was to ascertain the uptake of the Monospot test in
      St. James's hospital in Dublin over the five years 2002-2006 and to determine the
      percentage of Monospot tests which had a positive result. Using the HIPE,
      Electronic Patient Record (EPR) and Patient Access System (PAS) databases in St.
      James's Hospital, a cohort of 593 patients with a diagnosis of tonsillitis or
      infectious mononucleosis was identified. Fourteen patients met the exclusion
      criteria as outlined below leaving a valid pool of 579 patients. It was
      ascertained whether each patient had a Monospot performed and if so, whether the
      result was positive or negative. In total, 249 (43.0%) of the included patients
      had a Monospot test. Of these, 197 (79.1%) were negative and 29 (11.6%) were
      positive. In 23 (9.2%) cases, no result was available. The uptake of the Monospot
      increased over the five years studied. A positive Monospot impacts on treatment
      and follow up. We therefore recommend that one is carried out in all patients
      presenting with acute tonsillitis.

PMID- 19772008
TI  - Severe hyperbilirubinaemia and kernicterus: more caution is needed in newborn
      jaundice surveillance.
AB  - Since the 1990s, there has been a re-emergence of cases of severe
      hyperbilirubinaemia and kernicterus. The current UK incidence of bilirubin
      encephalopathy is 0.9/100,000 with a higher reported incidence in some countries.
      Three otherwise healthy newborn infants, who presented with severe
      hyperbilirubinaemia, including one who developed kernicterus, are reported here.
      Some of the current challenges in newborn jaundice surveillance are highlighted.

PMID- 19772009
TI  - Pleuropulmonary blastoma type I following resection of incidentally found
      congenital lobar emphysema.
AB  - Pleuropulmonary blastoma (PPB) is an aggressive tumour accounting for less than
      1% of all primary malignant lung tumours in the paediatric population. It can be
      associated with cystic pulmonary lesions, which may be evident at the time of
      diagnosis or predate the appearance of the tumour. There are contradictory
      reports about the value of prophylactic resection of pulmonary cysts in
      protecting patients from developing PPB. We report an individual case where
      asymptomatic congenital lobar emphysema was incidentally picked up on CXR.
      Following a period of surveillance the lesion was resected due to increasing
      size. The histology of the lesion revealed PPB Type I.

PMID- 19772010
TI  - An audit of traumatic nerve injury.
AB  - The impact of trauma in the Irish healthcare setting is considerable. We present
      the results of a retrospective assessment of referrals to a Neurophysiology
      department for suspected traumatic nerve injury. A broad range of traumatic
      neuropathies was demonstrated on testing, from numerous causes. We demonstrate an
      increased liklihood of traumatic nerve injury after fracture / dislocation (p =
      0.007). Our series demonstrates the need for clinicians to be aware of the
      possibility of nerve injury post trauma, especially after bony injury.

PMID- 19772011
TI  - Conservative management of placenta accreta.
AB  - Two case reports of conservative management of placenta accreta in primiparous
      women are reported. Initial attempts to evacuate the uterus via manual removal
      and routine oxytocics were unsuccessful. The patients were counselled regarding
      further management options, surgical (hysterectomy), radiological guided arterial
      embolisation, medical (methotrexate, prostaglandins, mifepristone) and
      conservative ("watchful waiting"). After a long discussion regarding the risks of
      haemorrhage and infection and emergency hysterectomy, both patients opted for a
      conservative approach and were discharged from hospital with the placenta still
      in situ. The patients were followed with weekly clinical and ultrasonic
      assessment. One patient had a spontaneous evacuation 43 days postnatally and the
      second 80 days postnatally. The fertility of both women was conserved but neither
      have attempted further pregnancy to date.

PMID- 19772012
TI  - The SM judgment and the Mental Health Act 2008.
AB  - The Mental Health Act 2008 was subject to little debate. This Act ensured that
      the detentions of involuntary psychiatric patients under the Mental Health Act
      2001 remained lawful. The direct costs of administering the Act are estimated at
      Euro 993,377, which could have provided 37 years of supported accommodation to
      the patient involved.

PMID- 19772013
TI  - A need for definition: a matter of life and death for human embryos.

PMID- 19772014
TI  - The decline of hysterectomy for benign disease.

PMID- 19772015
TI  - Pulmonary thrombo embolism in pregnancy.

PMID- 19772016
TI  - Isolated common peroneal nerve palsy in sarcoidosis.

PMID- 19772017
TI  - Alzheimer's care: a primer for in-home care.

PMID- 19772018
TI  - The symbiosis of geriatric care management and in-home care: assisting the
      cognitively impaired.

PMID- 19772019
TI  - Caring for seniors with Alzheimer's.

PMID- 19772020
TI  - Striving for safety: a falls prevention initiative for home care clients with
      dementia.

PMID- 19772021
TI  - Providing supportive care to the client with Alzheimer's disease.

PMID- 19772022
TI  - Becoming an Alzheimer's Whisperer: taking the program to market.

PMID- 19772023
TI  - Virtual psycho-educative support groups for caregivers of persons diagnosed with
      dementia.

PMID- 19772024
TI  - Massachusetts seeks to strengthen the home care and physician partnership.

PMID- 19772025
TI  - Sales force of the future: part one.

PMID- 19772026
TI  - Simply the best.

PMID- 19772027
TI  - The number one management problem in home care.

PMID- 19772028
TI  - On a clear day... you can see tomorrow.

PMID- 19772029
TI  - Home care and telestroke.

PMID- 19772030
TI  - Autistic rider.

PMID- 19772031
TI  - Happy birthday, Medicare.

PMID- 19772032
TI  - ECG of the month: right-axis deviation of the QRS complex with precordial R-wave
      regression. Situs inversus with mirror-image dextrocardia, sinus rhythm, and a
      long P-R interval.

PMID- 19772033
TI  - A 32-year-old woman with chest pain, hematemesis, and thrombocytopenia.
AB  - The diagnosis of TTP should be considered in any clinical scenario in which
      hemolysis and thrombocytopenia are present. If other secondary causes are ruled
      out, therapy should instituted as rapidly as possible. TPE remains the standard
      of care for TTP. In emergent situations where TPE is not immediately available,
      infusion of FFP at 15 mL/kg per day and initiation of glucocorticoids is
      acceptable.

PMID- 19772034
TI  - Radiology case of the month: a young man with persistent leg pain. Osteoid
      osteoma.

PMID- 19772035
TI  - Signet-ring-cell adenocarcinoma of the myocardium presenting as persistent
      pleural effusions.
AB  - We report a case of persistent bilateral pleural effusions in a 40-year-old man
      with echocardiographic findings suggesting constrictive pericarditis. However,
      this was not supported by cardiac catheterization. The pleural fluid was
      transudative in nature and was negative for acid-fast bacilli (AFB) and
      malignancy. Radiographic studies did not define an underlying etiology. Filling
      defects were found in the subclavian and jugular veins bilaterally but no
      pulmonary embolus was found on computed tomographic (CT) scan. The patient
      developed sudden and profound hypoxia and subsequent pulseless electrical
      activity and expired. At autopsy the myocardium, pericardium, and proximal blood
      vessels were invaded with signet-ring-cell adenocarcinoma. Another focus of this
      tumor also was found in the spleen but not in the stomach, suggesting the heart
      may have been primary. If so, this is the first reported case of primary cardiac
      signet-ring-cell adenocarcinoma.

PMID- 19772036
TI  - Ganglioglioma in the cerebellopontine angle of an adult without seizures.
AB  - We present a rare case of an adult patient without seizures who is found to have
      a ganglioglioma occurring in the cerebellopontine angle. A 52-year-old woman with
      ataxia, headaches, and falling episodes underwent neuroimaging. Magnetic
      resonance imaging (MRI) revealed a smooth, somewhat lobulated mass in the left
      cerebellopontine angle. The mass was hypointense on T1-weighted imaging,
      hyperintense on T2-weighted imaging, and did not enhance after administration of
      gadolinium. Left retromastoid craniectomy was performed, and the mass was noted
      to be exophytic from the brain stem. The exophytic component was resected. Light
      microscopic findings were consistent with ganglioglioma. This was confirmed with
      immunohistochemical studies. Ganglioglioma is a rare tumor of the central nervous
      system that typically presents with seizures in children and young adults.
      Occurrence of this tumor in the cerebellopontine angle is extremely unusual; this
      rarity is magnified by its occurrence in an adult patient without a history of
      seizures. Our case illustrates that ganglioglioma should be considered in the
      differential diagnosis of cerebellopontine angle masses at any age. This appears
      to be especially true when dealing with masses that are non-enhancing on imaging.

PMID- 19772037
TI  - Ventricular septal defect from a gunshot to the buttock.

PMID- 19772038
TI  - Do probiotics have a role in the management of inflammatory bowel disease?
AB  - Inflammatory bowel disease treatments have generally revolved around
      immunological manipulations to reduce inflammation of the gastrointestinal tract.
      Bacterial interactions with the gastrointestinal epithelium may be a trigger for
      inflammatory changes which occur in the gut. Antibiotics have been shown to alter
      disease activity in Crohn's disease. Probiotics (live microorganisms)
      administered for therapeutic purposes have been proposed due to the possibility
      of their altering the interaction of the gut mucosa with enteric bacteria.
      Extensive randomized trials are lacking in this area at this time. Current trials
      indicate the possibility of maintaining remission in pouchitis (non-specific
      inflammation) and the potential for inducing and maintaining remission in
      ulcerative colitis. Trials in Crohn's disease have shown mixed results.

PMID- 19772039
TI  - Retropharyngeal/anterolateral approach for C2 corpectomy.
AB  - Instability of the high cervical spine, particularly C1 and C2, is commonly
      treated via a posterior approach. Access to this region via transoral approaches
      is often avoided due to the high risk of wound contamination, limited exposure,
      and lack of experience on the part of the surgeon. We present a 48-year-old man
      exhibiting complete C2 vertebral body involvement by multiple myeloma with a
      pathologic fracture, which we treated via the anterolateral/retropharyngeal
      approach to the high cervical spine. The anterolateral/retropharyngeal approach
      provides relatively easy access to the anterior arch of C1 and to the vertebral
      bodies of C2-4 and can be applied to a variety of different conditions. In
      addition, this approach may be a viable alternative to the transoral route and
      its associated morbidities.

PMID- 19772041
TI  - Why do we watch it?

PMID- 19772040
TI  - Interstitial pneumonitis in the transplant patient: consider sirolimus-associated
      pulmonary toxicity.
AB  - Interstitial pneumonia in a transplant patient can have a varied etiology.
      Sirolimus (Rapamycin; Rapamune) is a popularly used immunosuppressant in solid
      organ transplantation that has anecdotally been associated with pulmonary
      toxicity. Sirolimus-induced pulmonary toxicity consists of a range of syndromes
      that is characterized by the presence of organizing pneumonia, interstitial
      pneumonitis, pulmonary alveolar proteinosis, focal fibrosis, or by the presence
      of alveolar hemorrhage. Diagnosis can be challenging and is usually made by
      exclusion of other etiologies. In this report we present two cases of sirolimus
      associated pulmonary toxicity with a review of the literature.

PMID- 19772042
TI  - Spotlight on social determinants was right on.

PMID- 19772043
TI  - A measure of hope.

PMID- 19772044
TI  - Mixed news.

PMID- 19772045
TI  - Plan of action. Physicians are working with the City of Minneapolis to keep kids
      from becoming repeat victims of violence.

PMID- 19772046
TI  - Tending victims, tackling crime. A northwestern Minnesota hospital takes on
      violence and abuse.

PMID- 19772047
TI  - Reclaiming girlhood. A program for runaway youths brings health care to sexually
      abused kids wherever they are.

PMID- 19772048
TI  - Cutting costs must not harm patients.

PMID- 19772049
TI  - Medicare payment needs fixing.

PMID- 19772050
TI  - Challenging an assumption. A pathologist questions shaken baby syndrome.

PMID- 19772051
TI  - The hidden toll of abuse.

PMID- 19772052
TI  - Shining light in dark places. Child abuse hurts a physician as well as her young
      patient.

PMID- 19772053
TI  - Beyond "Do you feel safe at home?" The physician's role in reducing intimate
      partner homicide.
AB  - Each year, more than a thousand women in the United States die as a result of
      intimate partner homicide. Firearms are involved in 60 percent of these murders.
      This article reviews the role firearms play in domestic violence and suggests
      actions physicians can take to reduce intimate partner homicide involving them.
      In addition to screening patients for domestic abuse, physicians can strive to
      improve data collection on intimate partner violence, foster better communication
      between victims and the police, and support policies that hold police officers
      and prosecutors accountable for taking guns out of the hands of abusers.

PMID- 19772054
TI  - How to screen for intimate partner violence.
AB  - Domestic violence affects individuals in every part of the world, regardless of
      age, economic status, race, religion, nationality, or educational background. In
      the United States, domestic violence affects as many as 3 million women each
      year. Physicians and other health care providers have a unique opportunity to
      screen their patients-both female and male-for domestic violence or abuse. This
      article describes signs and symptoms of domestic violence that physicians should
      look for when seeing patients in the medical office or hospital and offers
      guidelines for initiating a discussion with patients who might be victims or
      abusers.

PMID- 19772055
TI  - Patient charting. Turning a routine activity into an opportunity for injury
      prevention.
AB  - Injuries can be predicted and prevented. The first step in doing so is gathering
      data about who was injured and how. Because injury data is based on documentation
      in patients' medical charts, physicians play an important role in injury
      prevention. This article describes how to document all types of injuries,
      including those that are self-inflicted or caused by abuse.

PMID- 19772056
TI  - Suicide rates in 2009. Do the economy and wars have an effect?
AB  - Suicide is a public health problem that claims the lives of approximately 1
      million people around the world each year. This article describes suicide rates
      in the United States and Minnesota and discusses potential effects of the economy
      on the rate, concerns regarding suicides in the Army, and what clinicians can do
      to make a difference in the lives of patients who may be at risk.

PMID- 19772057
TI  - Nonfatal suicide attempts and other self-inflicted harm. Beltrami County youths,
      2002-2006.
AB  - Following a highly publicized murder-suicide by a high school student in Beltrami
      County, Minnesota, the Minnesota Department of Health initiated an investigation
      into suicide attempts and self-inflicted harm (SA/SIH) among youths in the county
      between 2002 and 2006. This article summarizes the results of that effort, which
      found an annualized rate of 356 hospital-treated SA/SIH per 100,000 population
      among Beltrami County residents ages 10 to 24 years--a rate more than 50% higher
      than that of other youths in Minnesota or the United States. In addition, the
      rate of SA/SIH for American Indian youths in Beltrami County was 2.5 times higher
      than that for white youths. An examination of medical history found 52% of the
      youths in this study had previously attempted suicide. This article also
      discusses several modifiable risk factors that were identified and potential
      interventions.

PMID- 19772058
TI  - Achieving a fulfilling educational pathway.

PMID- 19772059
TI  - The benefits of professional supervision.

PMID- 19772060
TI  - What's so funny?

PMID- 19772061
TI  - Compassion and caring still essential.

PMID- 19772062
TI  - Where to for RN scope of practice?

PMID- 19772063
TI  - ENS--is the debate nearly over?

PMID- 19772064
TI  - Examining the benefits of professional clinical supervision.

PMID- 19772065
TI  - The SOAP format enhances communication.

PMID- 19772066
TI  - Reducing the impact of preoperative fasting on patients.

PMID- 19772067
TI  - Tragedy a source of inspiration.

PMID- 19772068
TI  - Bringing the family nurse practitioner role from Wisconsin to Martinborough.

PMID- 19772069
TI  - From teaching to nursing with joy.

PMID- 19772070
TI  - Referendum poses risk to child discipline law.

PMID- 19772071
TI  - Overseas nurses suggest improvement to registration process.

PMID- 19772072
TI  - Keep on practising!

PMID- 19772073
TI  - Protect youself.

PMID- 19772074
TI  - Why are we waiting?

PMID- 19772075
TI  - Building a kaupapa Maori service.

PMID- 19772076
TI  - When enough is enough.

PMID- 19772077
TI  - Case report: acute retinal necrosis.

PMID- 19772078
TI  - Sialendoscopy in Delaware.

PMID- 19772079
TI  - How to set your fee schedule: experts advise updating it every 3 to 12 months.

PMID- 19772080
TI  - Heart disease: The number one killer in the country.

PMID- 19772081
TI  - How to maximize the effectiveness of a home care cardiac disease program.
AB  - Cardiac disease is one of the fastest growing illnesses in the U.S. According to
      Reuters Health (2002), it is predicted that by 2030 there will be 1.5 billion
      people in the U.S. with hypertension. According to the American Heart
      Association, in 2009 the cost of managing patients with cardiac disease is
      projected to be more than $304.6 billion, including health care services,
      medication, and lost productivity (2009).

PMID- 19772082
TI  - Telehealth-supported innovation in home care.

PMID- 19772083
TI  - Innovations in home care technology.

PMID- 19772084
TI  - An evolutionary home care model for chronic disease management.

PMID- 19772085
TI  - Ten steps to building a successful telehealth program.

PMID- 19772086
TI  - Implications of the HITECH Act of 2009.

PMID- 19772087
TI  - The future of telehealth monitoring.
AB  - Among senior hospital executives, integrated health care delivery networks (IDNS)
      and managed care organizations around the country, chronic patient population
      management is fast becoming a frequent topic of discussion. More than 100 million
      people in the U.S. suffer from some type of chronic condition, an astounding
      number for the country's health and pocketbook. The objective with these chronic
      patient populations is to keep them connected to the existing care continuum,
      managing their health while at home, as well as to control their entry into acute
      care setting, if and when that level of care is required.

PMID- 19772088
TI  - Information technology orientation: teach your clinicians the skills they need to
      succeed.

PMID- 19772089
TI  - Make service your nature.

PMID- 19772090
TI  - New developments and a call to action for home care on Capitol Hill.

PMID- 19772091
TI  - Jump into social media with a successful home care blog.

PMID- 19772092
TI  - OASIS C: what clinicians really think.

PMID- 19772093
TI  - It starts with us.

PMID- 19772094
TI  - BBVI.

PMID- 19772095
TI  - Tele-triage: success depends on advanced nursing skills.

PMID- 19772096
TI  - The heart of the matter.

PMID- 19772098
TI  - Damage control needed: STAT.

PMID- 19772097
TI  - ISMP medication safety alert! Benzocaine spray and methemoglobinemia.

PMID- 19772099
TI  - Creating balance in your life.

PMID- 19772100
TI  - Patients' page. Athletic mouthguards.

PMID- 19772101
TI  - Clinical management of root caries.

PMID- 19772102
TI  - LOVE dentistry, even in a recession!

PMID- 19772103
TI  - Balanced wellness strategies for the dental professional.

PMID- 19772104
TI  - Provisional restoration to preserve interdental papillae in the esthetic zone: a
      case report.
AB  - Patients are more aware of dental esthetics than ever before and demand more than
      just a replacement of a missing tooth. The selection of the type of provisional
      restoration can significantly influence esthetics during the period of implant
      integration and soft tissue healing. A restoration that preserves or helps to
      regenerate interdental papillae has always been a challenge for both experienced
      and inexperienced practitioners. The case presented here shows how a fiber
      reinforced provisional restoration was used immediately after extraction to
      preserve the interdental papillae. This is a good alternative to removable
      provisional restorations as it has minimal bulk, provides the security of a fixed
      restoration and the predictability of molding tissue while it is healing.

PMID- 19772105
TI  - Periodontal maintenance therapy: an integral part of dental practice. Case
      reports on three periodontally involved patients.
AB  - Periodontal maintenance therapy is an integral aspect of any general dental or
      specialist practice. Numerous studies have indicated that periodontal therapy in
      the absence of a carefully designed maintenance program invariably results in the
      relapse of the disease condition. Accordingly, dental practices that provide
      periodontal care without a maintenance program deal with significant patient
      management and disease management issues. In this article, three cases are
      presented with varying levels of disease severity but all sharing the common
      trait of having being enrolled in a good maintenance program with positive
      treatment outcomes.

PMID- 19772106
TI  - The changing face of ACC.

PMID- 19772107
TI  - Dental treatment profile of New Zealand Defence Force personnel.
AB  - OBJECTIVE: To evaluate the dental treatment provided over one year to serving
      personnel and new entrants in the New Zealand Defence Force (NZDF). METHOD:
      Dental treatment data from 4,380 personnel in the 12 months following their last
      annual dental examination were retrieved and evaluated from electronic data
      archives. These included all treatment provided for 2000 randomly-selected
      regular serving personnel and for all 2380 new entrants entering the Service in
      the years 2005 and 2006. RESULTS: Treatment data were recorded for 1770 (88.5%)
      of the 2000 serving personnel in the year following their last dental
      examination. Excluding examinations and radiographs, treatments averaged 2.3 per
      person. Amalgam and composite restorations contributed 40%, preventive and oral
      hygiene services 44%, and tooth extractions 6% of treatments; the "other"
      category amounted to 10% of treatments. For the 2380 new entrants, treatment data
      were recorded for 1959 (82.3%) during their first year of service. Treatments
      averaged 3.6 per person; amalgam and composite restorations contributed 58%,
      preventive and oral hygiene services 25%, and extractions 10%. The remaining 10%
      of treatment items recorded comprised a diverse range of procedures. CONCLUSIONS:
      The level of treatment provided was low for both serving personnel and new
      entrants. Ninety percent of teeth were present and functional. Amalgam and
      composite restorations, preventive care and oral hygiene procedures made up the
      majority of treatment provided.

PMID- 19772108
TI  - A qualitative study of the role of dental therapy in New Zealand.
AB  - OBJECTIVES: To investigate the role of the dental therapy profession in New
      Zealand, identifying the foundation of the profession, and the influences that
      have shaped its role. DESIGN: Qualitative study incorporating transcripts from
      oral archives, national questionnaires, and semi-structured interviews with key
      people of influence among the oral health professions. METHODS: A selection of
      data was ordered into a written sequence and presented, to demonstrate key
      influencing factors in the introduction, training and work of New Zealand's
      dental nurses. RESULTS: Education for the dental therapy profession was preceded
      by the school dental nurse vocation and, despite the intention for the dental
      nurse's role to be one of 'forestalling disease' and 'prevention', the eventual
      role was very different. CONCLUSIONS: The study provides evidence of the valuable
      role of Dental Therapy in New Zealand's public health sector, but whether the
      role has been utilised most effectively is questionable, particularly when
      considering the original objectives that were given when the School Dental Nurse
      concept was first introduced.

PMID- 19772109
TI  - Endodontic treatment of a mesotaurodont maxillary first molar: a case report.
AB  - Taurodontism is an abnormal morphological trait of tooth shape, which usually
      occurs in multi-rooted teeth. An enlarged pulp chamber and apical displacement of
      the pulpal floor are characteristics. Endodontic treatment ofa taurodont tooth
      may be very difficult because it requires special care in identifying and
      treatment of the complex root canal system. The endodontic treatment ofa
      taurodont maxillary first molar is presented.

PMID- 19772110
TI  - The Dimensions of Expansion: report of the 2007 NZAO Symposium.
AB  - The biennial symposium of the Education, Research and Development Group (ERDG) of
      the New ZealandAssociation of Orthodontists (NZAO) was held in Queenstown on
      August 17 and 18, 2007. Following a well-tested format, the symposium considered
      the effects of expansion of the dental arches in the three planes of space and
      over time, a timely but difficult topic given the current fashion to avoid the
      extraction of teeth to correct dental crowding. The findings reported here
      represent the consensus reached by delegates attending the symposium.

PMID- 19772111
TI  - "We gave good patients mercury in burr boxes." A view of mercury from its earlier
      use in the School Dental Service to contemporary dental practice.

PMID- 19772112
TI  - Most cited: number 6. A comparison of the heat production and mechanical
      efficiency of diamond instruments, stones, and burs at 3,000 and 60,000 r.p.m.

PMID- 19772113
TI  - Reversing patient inactivity and isolation.

PMID- 19772114
TI  - Challenges of diffuse axonal injury diagnosis.
AB  - "This can't be right. Jay is in a vegetative state following a severe traumatic
      brain injury (TBI), but his computed tomography scan is essentially normal. How
      am I going to explain this to his mom?" This is a conversation I overhear among
      my rehabilitation nurse colleagues from time to time. Jay has a type of brain
      trauma called diffuse axonal injury (DAI). Recent statistics from the National
      Centers for Injury Prevention and Control (NCIPC, 2006) indicate 1.4 million
      people sustain a TBI each year in the United States. The leading causes of TBI
      are falls (28%), motor vehicle accidents (20%), being struck by or against an
      object (19%), and assaults (11%; NCIPC). DAI, one of the most important causes of
      cognitive dysfunction after TBI (Sugiyama et al., 2007), occurs in a more
      widespread pattern in certain regions of the brain than the localized zone of
      focal injuries. It is one of the most devastating forms of TBI and a common cause
      of vegetative state and severe disability. DAI occurs in 40%-50% of all patients
      who are hospitalized from TBI (Meythaler, Peduzzi, Eleftheriou, & Novack, 2001).

PMID- 19772115
TI  - Expanding the scope of staff education: brain injury to polytrauma.
AB  - Staff members who care for the polytrauma population need diverse educational
      programs even if they have many years of experience working in the brain-injury
      rehabilitation field. This article explores key concepts that help guide
      rehabilitation nursing practice, strengthen clinical skills, increase family
      involvement, and identify educational resources.

PMID- 19772116
TI  - APN knowledge, self-efficacy, and practices in providing women's healthcare
      services to women with disabilities.
AB  - Women with disabilities require the same gynecological and reproductive
      healthcare services as women without disabilities, yet they often experience
      difficulty obtaining them. Advanced practice nurses (APNs) increasingly provide
      primary care services that include women's health care, yet their influence on
      this population has not been systematically examined. This study examined the
      practices, environments, knowledge, and self-efficacy of APNs in Texas regarding
      provision of women's health care to women with disabilities. The study's
      respondents are 744 women who replied to a mailed survey. The results reveal that
      while nurses do not lack knowledge, work environments do not support competent
      care of women with disabilities and practices do not always follow national
      guidelines. Predictors of self-efficacy in provision of health care to women with
      disabilities were status as a women's health nurse practitioner, previous
      rehabilitation experience, high knowledge scores, and a working environment
      perceived as accessible. Until changes are made in APN education and
      environmental barriers are addressed, APNs may not be able to provide optimal
      women's healthcare services to women with disabilities.

PMID- 19772117
TI  - Medication safety series: take charge!
AB  - Nurses have read the statistics on the numbers of prescription medications
      seniors take each day and the pitfalls and diverse problems that occur as a
      result. Various scenarios contribute to this problem: multiple healthcare
      providers prescribe medications; the use of over-the-counter products and herbs
      or alcohol cause medication interactions; and patients increase, decrease, skip,
      or repeat doses. When medications are not taken correctly, an increase in the
      number of physician or emergency department visits and hospitalizations results.
      Patients who come to a rehabilitation unit after joint replacement or hip-pinning
      surgery, stroke, or for treatment of other conditions may be prescribed
      medications that differ from the drugs they were taking at home. These patients
      and their families need to learn how to safely take their new medications. This
      presentation describes how five nurses developed a medication safety program
      consisting of four segments: Making Your Medication List; Talking to Your
      Healthcare Team About Your Medications; Safely Storing, Taking, and Destroying
      Your Medications; and Knowing the Difference Between Allergies, Side Effects, and
      Interactions. This article also describes the development of the script and
      PowerPoint program, lessons learned from the first presentation, and implications
      for rehabilitation nurses. The information presented in this series can help
      patients and families take charge of their medications. The team of community
      educators who wrote this article encourages the integration of this program into
      readers' local patient communities because standards of care and resources vary
      in the communities that nurses serve.

PMID- 19772118
TI  - Stroke caregivers share ABCs of caring.
AB  - New stroke caregivers (N = 36) participated in a Web-based intervention that
      provided support and education and included exchanging e-mail messages in a
      discussion group. A male spousal caregiver posted a poem in his final message at
      the end of 1 year of participation in this discussion group. He used each letter
      of the alphabet to choose a word that represented a theme for what he had
      discovered while caring for his wife. A secondary analysis project examined
      narrative data from all caregivers' e-mails to see whether support existed for
      the word themes in the ABCs poem. 2,148 e-mails were read and examined using
      content analysis to get a sense of the meaning of the content, and then key words
      were identified that matched each of the poem's word themes. Other caregivers' e
      mail examples verified all 26 word themes of the ABCs poem. Nurses can use these
      themes when providing education and support interventions to stroke caregivers
      new to their new role.

PMID- 19772119
TI  - Postadmission dehydration: risk factors, indicators, and outcomes.
AB  - Detecting and treating dehydration in hospitalized patients is critical because
      of the adverse outcomes associated with this condition. Using a case-control
      design, this study estimated the incidence, risk factors, and outcomes of
      dehydration in hospitalized adults. The overall incidence rate for developing one
      of three ICD-9 codes for dehydration during a hospital stay was 3.5%. Cases and
      controls differed significantly on a number of clinical variables on admission; a
      large percentage of patients may have had dehydration on admission to the
      hospital. Mortality rates at 30 and 180 days postdischarge were significantly
      higher when dehydration was present. Patients may be discharged to rehabilitation
      settings in a dehydrated state, which prolongs recovery. Despite the increased
      risk for dehydration and higher rates of hospitalization in older populations,
      little systematic research has addressed the risk factors for and indicators of
      dehydration in hospitalized patients.

PMID- 19772120
TI  - Integrating educational technology into the basic sciences.

PMID- 19772122
TI  - Thinking globally, acting locally.

PMID- 19772123
TI  - Challenges and opportunities for nurses and midwives.
AB  - The significant challenges and opportunities confronting nursing and midwifery
      were the main focus of the 28th QNU Annual Conference held in Brisbane last
      month.

PMID- 19772125
TI  - The new modern nurses' award.

PMID- 19772126
TI  - QNU member wins appeal against nursing tribunal.
AB  - In a small rural community, a registered nurse with thirty years of experience
      regularly visits her former client. She used to care for him as his community
      nurse. Now she cares about him as a friend. She feeds his cat and attends to his
      personal affairs at his request. Little does she know that she is to become a
      beneficiary under his will; little does she know that accepting his bequest will
      come at the cost of losing her employment, the Nursing Tribunal cancelling her
      registration and the media ambushing her at her workplace.

PMID- 19772127
TI  - Unexpected patient death or coronial inquest? Are you really covered?

PMID- 19772128
TI  - H1N1 influenza: what you need to know.
AB  - With the H1N1 influenza anticipated to peak in Queensland this month, it is
      important that all QNU members are up-to-date on the latest information and
      advice. The QNU has received regular briefings from Queensland Health on their
      response to the progression of the pandemic, and it is expected there will be
      significant increased demand for critical care and emergency department services,
      with flow-on effects to elsewhere in the health system. If this occurs, it will
      necessitate the deployment of nurses and other health care workers to those
      areas. Queensland Health are currently planning risk management strategies based
      on the experiences interstate as well as with pandemics overseas.

PMID- 19772129
TI  - Safety and security update.
AB  - Despite resolution of the initial dispute that occurred in early 2008 regarding
      safety and security issues for nurses employed on the Torres Strait Outer
      Islands, concerns continue about the ongoing sustainability of health services in
      this remote location as well as for Queensland Health-run accommodation across
      the state.

PMID- 19772130
TI  - Guest editorial. Developing human resources for health in the Pacific.

PMID- 19772131
TI  - Pacific basin health worker training in the United States-Affiliated Pacific
      Islands: needs assessment and priorities for a continuing health care
      professional development program: executive summary.
AB  - The United States-Affiliated Pacific Islands (USAPI) include the U.S. Flag
      Territories of American Samoa and Guam, the Commonwealth of the Northern Mariana
      Islands (CNMI) and three Freely Associated States: the Federated States of
      Micronesia (FSM), the Republic of the Marshall Islands (RMI) and the Republic of
      Palau. These six jurisdictions span four time zones and are separated by over
      4,000 miles of the Pacific. There has been a well documented need for continuing
      education (CE)for health workers in the USAPI region. This executive summary
      highlights key points from a series of CE needs assessments conducted in the
      region in 2004. These reports are presented in their entirety (pages 31-88) in
      this issue.

PMID- 19772132
TI  - A pilot evaluation of distance education modalities for health workers in the
      U.S.-Affiliated Pacific Islands.
AB  - BACKGROUND: Healthcare workers in many parts of the U.S.-Affiliated Pacific
      Islands (USAPI) have limited access to continuing education. Barriers to
      traditional on-site continuing education programs include the diversity of
      educational needs, limited health staffing, the distances between islands and
      associated high travel costs. A pilot evaluation of distance education modalities
      was conducted among USAPI healthcare workers. METHODS: Three distance education
      modalities (live videoconference, live audioconference and a recorded computer
      based format) were evaluated in comparison to live lecture during two separate
      half-day educational programs in Pohnpei, Federated States of Micronesia, in June
      2004. Participants from the USAPI included 59 nurses, doctors, dentists and other
      healthcare workers who were assigned to different educational modalities for two
      training modules (diabetes/oral health and metabolic syndrome). We conducted pre
      and post-tests and obtained participant feedback. RESULTS: Comparison of pre-test
      and post-test scores showed statistically significant score increases among the
      live lecture and videoconference group for the diabetes/oral health module and
      among all three distance education modalities for the metabolic syndrome module.
      Participants expressed a high degree of interest in each of the distance
      education modalities. Computer-based training was well-accepted even by health
      workers with little prior computer experience. CONCLUSIONS: This pilot study
      validates the ongoing development and evaluation of distance education resources
      as part of a comprehensive approach to improving continuing education in the
      USAPI. The results have been used to guide continuing education efforts in the
      region.

PMID- 19772133
TI  - American Samoa assessment for a continuing health care professional development
      program.
AB  - In 2003, the University of Hawai'i Department of Family Medicine & Community
      Health entered a 4-year cooperative agreement with the U.S. Health Resources and
      Services Administration to establish the "Pacific Association for Clinical
      Training" (PACT). PACT's goal is to develop effective distance education methods
      to improve the education and skills of healtcare professionals in the U.S.
      Affiliated Pacific Island nations. To determine the situation existing in 2004,
      one of PACT's first projects was to perform site visits to each jurisdiction,
      conducting needs assessments through interviews with key healtcare professionals,
      hospital administrators, and government officials. This article highlights
      findings of PACT's American Samoa assessment. Meant to establish a baseline for
      future reference, all data are those collected in 2004/2005 and have not been
      updated.

PMID- 19772134
TI  - Commonwealth of the northern Marianas assessment for a continuing health care
      professional development program.
AB  - In 2003, the University of Hawai 'i Department of Family Medicine and Community
      Health entered a four-year cooperative agreement with the U.S. Health Resources
      and Services Administration to establish the "Pacific Association for Clinical
      Training" (PACT). PACT's goal is to develop effective distance education methods
      to improve the education and skills of healthcare professionals in the U.S.-
      Affiliated Pacific Island Nations. To determine the situation existing in 2004,
      one of PACT's first projects was to perform site visits to each jurisdiction,
      conducting needs assessments through interviews with key healthcare
      professionals, hospital administrators, and government officials. This article
      highlights findings of PACT's Assessment of the Commonwealth of the Northern
      Mariana Islands (CNMI). Meant to establish a baseline for future reference, all
      data were that collected in 2004/2005 and have not been updated.

PMID- 19772135
TI  - Guam assessment for a continuing health care professional development program.
AB  - In 2003, the University of Hawai 'i (UH) Department of Family Medicine and
      Community Health entered a 4-year cooperative agreement with the U.S. Health
      Resources and Services Administration to establish the "Pacific Association for
      Clinical Training" (PACT). PACT's goal is to develop effective distance education
      methods to improve the education and skills of healthcare professionals in the
      U.S.- Affiliated Pacific Island nations. To determine the situation existing in
      2004, one of PACT's first projects was to perform site visits to each
      jurisdiction, conducting needs assessments through interviews with key healthcare
      professionals, hospital administrators, and government officials. This article
      highlights findings of PACT's Guam Assessment. Meant to establish a baseline for
      future reference, all data are those collected in 2004/2005 and have not been
      updated.

PMID- 19772136
TI  - Chuuk assessment for a continuing health care professional development program.
AB  - In 2003, the University of Hawai'i Department of Family Medicine and Community
      Health entered a four-year cooperative agreement with the U.S. Health Resources
      and Services Administration to establish the "Pacific Association for Clinical
      Training" (PACT). PACT's goal is to develop effective distance education methods
      to improve the education and skills of health care professionals in the U.S.
      Affiliated Pacific Island nations. To determine the situation existing in 2004,
      one of PACT's first projects was to perform site visits to each jurisdiction,
      conducting needs assessments through interviews with key health care
      professionals, hospital administrators, and government officials. This article
      highlights findings of PACT's Assessment of Chuuk State, Federated States of
      Micronesia. Meant to establish a baseline for future reference, all data are
      those collected in 2004/2005 and have not been updated.

PMID- 19772137
TI  - Kosrae assessment for a continuing health care professional development program.
AB  - In 2003, the University of Hawai'i Department of Family Medicine and Community
      Health entered a 4-year cooperative agreement with the U.S. Health Resources and
      Services Administration to establish the "Pacific Association for Clinical
      Training" (PACT). PACT's goal is to develop effective distance education methods
      to improve the education and skills of healthcare professionals in the U.S.
      Affiliated Pacific Island nations. To determine the situation existing in 2004,
      one of PACT's first projects was to perform site visits to each jurisdiction,
      conducting needs assessments through interviews with key healthcare
      professionals, hospital administrators and government officials. This article
      highlights findings of ACT's Assessment of Kosrae State, Federated States of
      Micronesia. All data were collected in 2004/2005 and have not been updated since
      it was to establish a baseline for future reference.

PMID- 19772138
TI  - Pohnpei assessment for a continuing health care professional development program.
AB  - In 2003, the University of Hawai'i Department of Family Medicine and Community
      Health entered a 4-year cooperative agreement with the U.S. Health Resources and
      Services Administration to establish the "Pacific Association for Clinical
      Training" (PACT). PACT's goal is to develop effective distance education methods
      to improve the education and skills of health care professionals in the U.S.
      Affiliated Pacific Island nations. To determine the situation existing in 2004,
      one of PACT's first projects was to perform site visits to each jurisdiction,
      conducting needs assessments through interviews with key healthcare
      professionals, hospital administrators, and government officials. This article
      highlights findings of PACT's Assessment of Pohnpei State, Federated States of
      Micronesia. Meant to establish a baseline for future reference, all data are
      those collected in 2004/2005 and have not been updated.

PMID- 19772139
TI  - Yap assessment for a continuing health care professional development program.
AB  - In 2003, the University of Hawai'i Department of Family Medicine and Community
      Health entered a 4-year cooperative agreement with the U.S. Health Resources and
      Services Administration to establish the "Pacific Association for Clinical
      Training" (PACT). PACT's goal is to develop effective distance education methods
      to improve the education and skills of healthcare professionals in the U.S.
      Affiliated Pacific Island nations. To determine the situation existing in 2004,
      one of PACT's first projects was to perform site visits to each jurisdiction,
      conducting needs assessments through interviews with key health care
      professionals, hospital administrators, and government officials. This article
      highlights findings of PACT's assessment of YAP State, Federated States of
      Micronesia. Meant to establish a baseline for future reference, all data are
      those collected in 2004/2005 and have not been updated.

PMID- 19772140
TI  - Palau assessment for a continuing health care professional development program.
AB  - In 2003, the University of Hawai'i Department of Family Medicine and Community
      Health entered a 4-year cooperative agreement with the U.S. Health Resources and
      Services Administration to establish the "Pacific Association for Clinical
      Training" (PACT). PACT's goal is to develop effective distance education methods
      to improve the education and skills of health care professionals in the U.S.
      Affiliated Pacific Island nations. To determine the situation existing in 2004,
      one of PACT's first projects was to perform site visits to each jurisdiction,
      conducting needs assessments through interviews with key health care
      professionals, hospital administrators and government officials. This article
      highlights findings of PACT's Palau assessment. Meant to establish a baseline for
      future reference, all data were collected in 2004-2005 and have not been updated.

PMID- 19772141
TI  - Republic of the Marshall Islands assessment for a continuing health care
      professional development program.
AB  - In 2003, the University of Hawai'i Department of Family Medicine and Community
      Health entered a 4-year cooperative agreement with the U.S. Health Resources and
      Services Administration to establish the "Pacific Association for Clinical
      Training" (PACT). PACT's goal is to develop effective distance education methods
      to improve the education and skills of healthcare professionals in the U.S.
      Affiliated Pacific Island nations. To determine the situation existing in 2004,
      one of PACT's first projects was to perform site visits to each jurisdiction,
      conducting needs assessments through interviews with key health care
      professionals, hospital administrators, and government officials. This article
      highlights findings of PACT's assessment of Republic of the Marshall Islands.
      Meant to establish a baseline for future reference, all data are those collected
      in 2004/2005 and have not been updated.

PMID- 19772142
TI  - Pacific Association for Clinical Training: e-learning telecommunication
      infrastructure assessment in the U.S.-Affiliated Pacific Islands.
AB  - This article summarizes the key points of a technology and telecommunications
      infrastructure assessment conducted by the University of Hawai'i
      Telecommunications and Information Policy Group (TIPG) in partnership with the
      Pacific Association for Clinical Training (PACT). It includes an overview of
      telecommunications infrastructure and services in the U.S.-Affiliated Pacific
      Islands (USAPI) jurisdictions. The objective is to review the technical capacity,
      in the USAPI, to support PACT e-learning programs and activities.
      Telecommunication infrastructure is fundamental for successful and sustainable e
      Learning programs. This article outlines the capabilities that may be available
      for multipurpose uses including health, education, research and other public
      service applications.

PMID- 19772143
TI  - Interdisciplinary problem-based learning as a method to prepare Micronesia for
      public health emergencies.
AB  - CONTEXT: The University of Hawai'i Pacific Basin Bioterrorism Curriculum
      Development Project has developed a problem-based learning (PBL) curriculum for
      teaching health professionals and health professional students about bioterrorism
      and other public health emergencies. These PBL cases have been incorporated into
      interdisciplinary training settings in community-based settings, such as in the
      small island districts of the U.S.-Affiliated Pacific Islands. METHODS:
      Quantitative and qualitative methods have been utilized in the evaluation of the
      PBL cases, PBL tutorials, and the accomplishment of learning objectives.
      FINDINGS: Evaluation of the PBL tutorials demonstrates that PBL is an educational
      and training modality appropriate for such settings. Participants found it
      helpful to learn in interdisciplinary groups. The educational process was
      modified in accordance with local culture. CONCLUSION: PBL is a useful
      educational modality for settings where healthcare staffing and available
      resources are limited.

PMID- 19772144
TI  - ICT capacity and human resource development in Island economies.
AB  - There is significant potential for Information Communication Technology (ICT) to
      play a major role in assisting economic and social development. However the
      technology, infrastructure, plans, and policies must be sustained and supported
      by people that have ICT skills, knowledge, and abilities. There are many facets
      in ICT capacity development in Island economies that this paper will touch upon:
      What are the best strategies for a country to develop a robust ICT skilled
      workforce at all levels which include the user, operator, administrator, and
      policy maker? What level of ICT education and training is needed? What are some
      of the challenges in delivering ICT education and training programs? What are
      some strategies for the design, development, and delivery of these programs? What
      are some examples of ICT capacity development programs in the Pacific Islands
      region?

PMID- 19772145
TI  - 'Healthcare is not something you can isolate from life in general": factors
      influencing successful clinical capacity building in the Pacific.
AB  - Capacity building assistance (CBA) uses multiple techniques, including training
      and technical assistance, to develop a sustainable infrastructure for healthcare
      agencies. Although there is some evidence that CBA is effective, much remains to
      be learned about the best ways to implement it. We assessed factors influencing
      the delivery of an HIV-related CBA project for health professional in the U.S.
      Affiliated Pacific Jurisdictions. We found some factors clearly facilitated CBA
      (e.g., implementing programs over long time periods), while others were clearly
      limiting influences (e.g., AIDS-related stigma). Lessons from this study can be
      applied to other CBA programs, where CBA providers can assess barriers and
      facilitators to implementation in order to target their services to the needs of
      local health experts.

PMID- 19772146
TI  - Meeting the challenge of HIV clinical training within 2.5 million square miles of
      the Pacific Ocean.
AB  - In the U.S.-Affiliated Pacific Islands, an area that encompasses 2.5 million
      square miles of ocean, the incidence of HIV is unknown. The area is susceptible
      to increased HIV activity because of high birth rates, high STD rates, a sexually
      active younger population, and a mobile population. The Hawai'i AIDS Education
      and Training Center (HAETC) has provided training in clinical care to the
      providers in the area since 2000. HAETC is part of the Pacific AIDS Education and
      Training Center that is part of a nationwide effort to educate and train
      professionals in HIV care. An adaptive multi-faceted curriculum appeared to be
      the best approach for training. HAETC has used conferences, mini-residencies,
      clinical consultations, and satellite conferencing.

PMID- 19772147
TI  - Developing a community-based collaboration to reduce cancer health disparities
      among Pacific Islanders in California.
AB  - Cancer is a leading cause of death for Asians and Pacific Islanders in the United
      States, but education and research efforts addressing the needs ofPacific
      Islanders in the continental U.S. is sparse. The purpose of this paper is to
      describe the development of a community-based participatory research network
      dedicated to addressing cancer health disparities among Chamorros, Marshallese,
      Native Hawaiians, Samoans and Tongans in Southern California. Community-based
      organizations (CBO) comprise the focus of the network, and their efforts have
      included increasing cancer-related awareness in their communities, developing
      capacities regarding cancer control, and initiating collaborative research
      efforts with academic partners. First year processes and outcomes are described,
      and specific examples are given from two CBO partners.

PMID- 19772148
TI  - Capacity building for cancer awareness in Hawai'i's foreign-born Filipino
      communities.
AB  - Community-based capacity building for cancer awareness, screening, diagnosis,
      treatment and survivorship is an integral component in addressing existing
      disparities apparent in many minority and underserved populations. Empowering
      community leaders within Hawai'i's Filipino immigrant community to increase
      awareness about cancer was the focus of a collaborative partnership between Asian
      American Network for Cancer Awareness, Research and Training (AANCART) and the
      National Cancer Institute's Cancer Information Service. A model curriculum was
      developed and tailored from existing resources and presented in a series of
      workshops designed in a "train-the-trainer" format. A total of 35 Filipino
      community leaders were trained and subsequently hosted community forums, which
      were designed to increase general awareness about cancer and promote regular
      cancer screening among Filipinos on the islands of Oahu and Kaua'i. Significant
      increases in knowledge related to cancer and prevention guidelines were apparent
      as a result of these community-wide efforts. In addition, the forums provided an
      opportunity for leaders and stakeholders within the Filipino community to engage
      in thoughtful inquiry related to existing barriers that prevent the dissemination
      of accurate cancer information, and also it also enabled them to engage in
      facilitated discussions about opportunities to empower community members in order
      to educate others. This collaborative partnership and the resulting community
      based intervention created the foundation for future efforts to increase cancer
      screening rates among Filipino immigrants, with a potential to impact and reduce
      existing cancer disparities in this population.

PMID- 19772149
TI  - Empowering natural clinical trial advocates: nurses and outreach workers.
AB  - Cancer clinical trials are essential to advancing the prevention and treatment of
      cancer, yet adult participation rates in clinical trials remain abysmal. Despite
      the essential contributions of clinical trials to science and medicine, adult
      participation in clinical trials remains exceedingly low, with only 2%-4% of all
      adult patients with cancer in the U.S. participating in clinical trials. Clinical
      trials accrual rates in Hawai'i follow this national trend of less than 3% of
      eligible patients participating in trials. Recognizing the need to increase
      awareness about clinical trials, the National Cancer Institute's Cancer
      Information Service-Pacific Region, through the Hawai'i Clinical Trials Education
      Coalition, has employed strategic dissemination plans to train and educate key
      target audiences, including registered nurses, nursing students, and community
      outreach workers about the availability of over 90 cancer clinical trials in
      Hawai'i. Previous research suggests that nurses often play a vital role in
      increasing a patient's understanding of clinical trials and may also act as a
      patient advocate in regards to participation in a clinical trial. A train-the
      trainer model curriculum was developed using the Clinical Trials Education Series
      (CTES), a collection of multi-level resources designed by the National Cancer
      Institute, to educate various constituents about clinical trials. The training
      curriculum and workshop format is adapted based on both formal and informal needs
      assessments conducted with audiences prior to the planned training, yet key
      elements remain central to the training model. In addition, an interactive,
      internet-based case study was developed using local place names and cultural cues
      to allow training participants to engage in realistic and practical methods for
      locating and sharing information about clinical trials with patients and the
      public. This training model has been implemented in a variety of settings
      including three statewide nursing conferences, two college campuses, and a
      community-based workshop. Evaluation results consistently indicate statistically
      significant increases in participants' knowledge and awareness related to
      clinical trials, and a cadre of trained clinical trials advocates is developing.
      Health professional advocacy towards adult participation in clinical trials is
      gaining momentum, with plans to expand the training model throughout the Pacific
      region.

PMID- 19772151
TI  - Maximizing successful pursuit of health careers in Micronesia: what to do?
AB  - The people of the U.S.- Associated Pacific Islands (USAPI) suffer significant
      health disparities when compared with industrialized countries. One explanation
      for this is lack of an adequate supply of skilled healthcare workers. The current
      research examines the factors that current health professionals from the region
      describe as helping and hindering them in their pursuit of health careers, as
      well as the barriers seen by students, educators and health professionals.
      METHODS: Two separate interview studies were conducted with a convenience sample
      of individuals in the five USAPI jurisdictions in the Northern Pacific. The first
      study utilized the responses of 15 individuals regarding the barriers to the
      pursuit of health careers in order to develop a logic model map of the most
      common problems in the pursuit of health careers. The second study involved in
      depth questions of 32 health professionals regarding barriers to and facilitation
      of health career training. Results were analyzed using constant comparative
      analysis. RESULTS: Interview results indicate that facilitators of students
      pursing health careers included having a family member working in healthcare, the
      desire to help people, available training opportunities and personal experiences.
      Facilitators of completion of training included family support, financial
      support, personal commitment and social support during school. Barriers to
      pursuit and completion of training included:limited academic preparation,
      exposure and guidance; family obligations, and other careers seen as being more
      desirable. DISCUSSION: Efforts to improve successful pursuit of health careers
      should start at the family level and must give a clear message to students that
      their goal is supported. Furthermore, there should be significant effort given
      to: improving the academic preparation provided for students, making career
      information available to students, and providing financial support, mentoring and
      guidance. Homesickness was a significant barrier that could be decreased by
      regional programs or a support system at locations with concentrated pockets of
      students from a given area.

PMID- 19772150
TI  - Evaluation of distance learning for health education.
AB  - The Hawai'i Unified Telehealth program is a distance learning health education
      program for rural communities, created with federal grant funding from the U.S.
      Department of Commerce and the National Institutes of Health. These grant funds
      helped develop a network of rural community learning centers that employ distance
      learning technologies to provide community-driven peer education to isolated
      areas across Hawai'i and Majuro, Republic of the Marshall Islands. In this
      article, the authors briefly describe the development of the ongoing health
      education program and the results of outcome evaluation completed at the end of
      the funding period.

PMID- 19772152
TI  - Ulithi Atoll health assessment: a peek at the health of rural Micronesia.
AB  - BACKGROUND: The health challenges of Micronesians are generally well known.
      However most of the health-related data collection occurs in the population
      centers and relatively little is known about the health of the residents of
      Micronesia's rural outer islands. This is of particular concern in the Federated
      States of Micronesia (FSM) where a large portion of the population lives on the
      outer islands. To gain a better understanding of the health issues facing the
      isolated outer islands of Micronesia, a health survey was performed on Ulithi
      Atoll in Yap, FSM. METHODS: A survey was created by the Yap State Department of
      Health Services and members of the Ulithian community. The survey was carried out
      on two of the four inhabited islands of Ulithi Atoll in July 2004. Both island
      communities actively participated in the survey providing translation and data
      gathering assistance. RESULTS: It was estimated that a >90% response rate for
      both islands was achieved. Analysis demonstrated that relative to the U.S., the
      Atoll's population experienced high rates of obesity (45%), hypertension (29%),
      and smoking (55%). Sixty-six percent of men surveyed reported alcohol use versus
      16% of women. Use of alcohol was markedly lower on Fatharai Island where a Chief
      had mandated abstinence. Preventative health screening was limited with over 80%
      of women having pap smear in the past 2 years. In addition, the community
      identified finances and transportation as the main difficulties in accessing
      healthcare. CONCLUSION: Overall, the research identified a number of health
      issues that require closer attention, in particular hypertension, overweight,
      obesity, alcohol misuse, smoking prevalence, betel nut/ tobacco chewing, and
      domestic violence. There is indication that the community may be ready to address
      some of these issues. The value of community action within cultural frameworks is
      apparent, and there may be potential to extend culturally-based approaches to
      address a broader range of issues.

PMID- 19772153
TI  - Age of onset of obesity, diabetes and hypertension in Yap State, Federated States
      of Micronesia.
AB  - BACKGROUND: As in many areas of the world, obesity, non-insulin dependent
      diabetes mellitus and hypertension have become major problems in Yap. METHODS:
      The population of the main island cluster of Yap age 2 years and older was
      surveyed and clinically evaluated. RESULTS: Obesity becomes common in people ages
      15-25 years, diabetes (random blood sugar 144) at ages 45-55 years, in females
      and 55-65 years in males, and hypertension (SBP>140 or DBP>90) at ages 25-35
      years. CONCLUSIONS: Female and male children might be targeted for obesity
      prevention as young as 15 years of age and tested for hypertension at 20 years
      and diabetes at 40 years.

PMID- 19772154
TI  - Health consequences and health systems response to the Pacific U.S. Nuclear
      Weapons Testing Program.
AB  - Between 1946 and 1958, the United States detonated 67 thermonuclear devices in
      the Pacific as part of their U.S. Nuclear Weapons Testing Program (USNWTP). The
      aggregate explosive power was equal to 7,200 Hiroshima atomic bombs. Recent
      documents released by the U.S. government suggest that the deleterious effects of
      the nuclear testing were greater and extended farther than previously known. The
      Republic of the Marshall Islands (RMI) government and affected communities have
      sought refress through diplomatic routes with the U.S. government, however,
      existing medical programs and financial reparations have not adequately addressed
      many of the health consequences of the USNWTP. Since radiation-induced cancers
      may have a long latency, a healthcare infrastructure is needed to address both
      cancer and related health issues. This article reviews the health consequences of
      the Pacific USNWTP and the current health systems ability to respond.

PMID- 19772155
TI  - "DC-OS": decentralized, on-site training; a sadly neglected option for building
      the Pacific Islands health workforce.

PMID- 19772156
TI  - Public health in the Republic of Palau: what we can learn from a small island
      country.
AB  - The Republic of Palau has a well-run public health system despite being a small,
      relatively isolated island country with limited resources and limited funds.
      Using interviews with key informants, participant observation in clinics
      throughout Palau, and a review of available reports, we identified themes locally
      regarded as central to the success of Palau's public health programs. These
      include a comprehensive definition of "health," a sense of community-ownership,
      creative efforts to identify effective behavioral modification techniques,
      efforts to improve internal training and infrastructure, quality assurance, the
      importance of leading by example, and a general willingness to collaborate and
      compromise. We suggest that recognition and application of these concepts would
      improve not only the public health systems and primary care settings of other
      Micronesian nations, but also help correct the increasingly dysfunctional
      healthcare of the United States.

PMID- 19772157
TI  - Developing a model of evidence-based public health practice that makes sense for
      the Pacific.
AB  - The new paradigm for public service organizations is summed up in the phrase
      "evidence-based practice," a concept grown from its origin in clinical medical
      practice to include a broad range of disciplines, including non-clinical
      approaches to disease prevention and health promotion. From a "global"
      perspective, this movement reflects the modernization policies of national
      governments that are intended to ensure effectiveness and increase accountability
      of publicly funded programs. It has also been fueled by rapid developments in
      information technology and the burgeoning growth in evidence-based research that
      forms the foundation of the movement. As the concept of evidence-based public
      health (EBPH) is exported to the Pacific, it will be imperative to keep in mind
      the historical and political forces that have shaped this movement, as these have
      important implications for attempts to advance the use of EBPH in Pacific Island
      communities. This commentary describes the basic format and evaluation results
      from an early attempt to introduce EBPH to public health workers in the Pacific
      at a 2-day workshop conducted at the Pacific Global Health Conference, June 13
      14, 2005. This article will conclude with recommendations for developing a
      culturally competent model for promoting EBPH practice among public health
      workers and policy makers who serve Pacific Island communities.

PMID- 19772158
TI  - How can the University of Hawai'i meet needs for public health education? Results
      of a students' needs assessment.
AB  - INTRODUCTION: A strong public health workforce is necessary to maintain the
      health and well-being of any community. Currently, the ability of the public
      health workforce to meet demand is being challenged in Hawai'i and the Pacific.
      This is due, in part, to the downsizing of the public health program at the
      University of Hawai'i (UH) in the year 2000. Knowing the current perceptions of
      the community in regards to public health and identifying ways to attract more
      students to public health are essential in reversing this trend. MATERIALS AND
      METHODS: Students from a class on needs assessment and program planning at the UH
      Department of Public Health Sciences assessed public health education needs. The
      class first conducted a literature review, focus groups, and interviews to inform
      the development of an on-line survey. The survey was sent to 200 individuals,
      including current public health students, faculty, workers, employers, and
      alumni. RESULTS: Of the 200 individuals invited to participate in the on-line
      survey, 128 (64%) responded. Almost half of the respondents were >50 years of
      age, and another 19% were between ages 41 and 50. Of the 118 who responded to
      this question, 85 had degrees in public health (80%from UH), and 62% had worked
      in public health for at least 10 years. However, only 50% of the total
      respondents knew that UH Masters of Public Health (MPH) and the Masters of
      Science (MS) programs were accredited. Forty percent or more of public health
      workers noted continuing education needs in 1) policy development and program
      planning skills, 2) analytical skills, 3) leadership and systems thinking skills,
      and 4) financial planning and management skills. Fully 43 of the respondents
      would consider applying to a DrPH program at UH, and 27 public health workers
      without an MPH would consider pursuing one. However potential students noted lack
      of time and timing of classes as barriers to attending school. Specific ideas for
      attracting students to public health were provided. Respondents also called for a
      greater commitment to public health from top leadership at UH and in Hawai'i.
      DISCUSSION: Findings confirm a need for a strong public health education program
      in Hawai'i and a lack of awareness about the MPH and MS programs at UH. Expanding
      options and opportunities for public health education will require better
      marketing and a cohesive commitment to public health education at UH.

PMID- 19772159
TI  - Imi Ho'ola: an educational model for disadvantaged students at the University of
      Hawai''i School of Medicine.
AB  - This paper describes an educational model that provides opportunities in medicine
      to students from disadvantaged backgrounds that have a commitment to serve in
      areas of need, and it presents guidelines on how this model could be adapted to
      various settings. From 1973 to 2002, the Imi Ho'ola Program (Hawaiian for "Those
      Who Seek to Heal") of the University of Hawai'i John A. Burns School of Medicine
      (JABSOM) has provided opportunities in medicine to 379 students from
      disadvantaged backgrounds. In 1995-1996, Imi Ho'ola underwent a transformation
      from a pre-medical enrichment program to a post-baccalaureate program that
      included provisional acceptance and financial support into JABSOM for students
      who successfully completed the program. As a result, the acceptance rate
      increased from 47.6% to 98.0%. In addition to provisional acceptance to JABSOM
      and financial support, the program's educational model incorporates five
      components, the key factors of the program's success: 1) JABSOM commitment and
      the institutionalization of the program; 2) emphasis placed on a comprehensive
      approach and the implementation of a curriculum and learning process that are
      aligned with JABSOM curricula; 3) faculty and staff who support the instructional
      methodology and work as a team to address students' needs; 4) assessment of
      students and systematic feedback regarding individualized education plans and
      academic and non-academic progress; and 5) a positive learning environment for
      students. Guidelines are provided in this article for consideration in adapting
      this educational model to other academic settings.

PMID- 19772160
TI  - The impact of the military presence in Hawai'i on the health of Na Kanaka Maoli.
AB  - The presence of the United States military on the islands of Hawai'i has affected
      the health and well-being of Native Hawaiians through large-scale historical
      processes, most notably Western colonization. This history has been shaped by the
      takeover of land for the purposes of military and commercial interests. We
      explore the effects that these interests have had upon the health of Native
      Hawaiian people, also known as Na Kanaka Maoli. Changes in policy and new program
      development are needed to improve the current poor health status of Native
      Hawaiians. In addition, potential avenues of research are proposed to evaluate
      the effects that the military presence has had upon the indigenous peoples of
      Hawai'i.

PMID- 19772161
TI  - Maintaining balance for a long voyage.
AB  - This article introduces cultural aspects of health, using Hokule'a, the voyaging
      canoe, as a model for maintaining balance on a long voyage through life.
      Maintaining balance encompasses physical, nutritional and mental health. This
      triangle is crucial for the well-being of a person. In the stress of the modern
      world we often disregard the basics in an effort to become more efficient and
      more productive, neglecting physical activity, eating fast foods instead of
      healthy meals, and forgetting our mental well-being. Eventually, this can lead to
      devastating co-morbidities. We discuss balanced nutrition, physical activity, and
      mental health, relating to living on the canoe, with lessons that can be applied
      to daily living.

PMID- 19772162
TI  - Reasons for homelessness among Micronesians at a transitional shelter in Hawai'i.
AB  - BACKGROUND: Over 6,000 people are homeless in the State of Hawai'i and a growing
      number are of Micronesian descent. This study looks at reasons for homelessness
      in the Micronesian population. METHODS: The authors conducted a retrospective
      chart review of 145 patients who were seen in a free student-run medical clinic
      at a transitional shelter in Hawai'i. Demographics and reasons for homelessness
      were compiled for the patients of Micronesian ancestry. RESULTS: Of the 56% of
      patients that were found to be of Micronesian ancestry, overcrowded housing was
      the most common reason leading to homelessness. CONCLUSION: Overcrowded housing,
      probably caused by poverty, along with social and cultural differences, likely
      play a significant role in the reasons for homelessness in Micronesian migrants.
      More research needs to be done to discern the reasons for, attitudes towards, and
      solutions for homelessness in this population.

PMID- 19772163
TI  - Pacific Association for Clinical Training (PACT): lessons learned and next steps
      in developing a sustainable continuing health professionals education system in
      the United States-Affiliated Pacific Island (USAPI) jurisdictions.
AB  - In response to the 1998 Institute of Medicine report, "Pacific Partnerships for
      Health ", acknowledging the need for the continuing education of health workers
      in the United States-Affiliated Pacific Island (USAPI) jurisdictions, the U.S.
      Health Resources and Services Administration (HRSA) awarded a grant (1999-2003)
      to the University of Washington for a continuing education project in the
      Pacific. When shortfalls in HRSA funding threatened continuation of the program,
      Pacific advocates aggressively made a case for refunding of this important
      project. In 2003, HRSA announced competitive funding for a new program for
      continuing education. The Department of Family Medicine and Community Health
      (DFMCH) at the University of Hawai'i (UH), John A. Burns School of Medicine
      (JABSOM) was awarded the HRSA Cooperative Agreement to run from September 2003
      through August 2007, creating PACT the Pacific Association for Clinical Training.
      PACT assembled a professional, community-based advisory board, most of whom were
      indigenous Pacific Islanders, and conducted a continuing clinical education needs
      assessment in every jurisdiction, subsequently developing and delivering programs
      utilizing distance education relevant to the needs of each USAPI jurisdiction.
      Priority health areas included diabetes, oral health and geriatrics, as mandated
      by HRSA. This report describes the processes, accomplishments, challenges and
      lessons learned from the project. PACT needs assessment reports for each
      jurisdiction and an executive summary are published as Original Articles in this
      issue of Pacific Health Dialog. As funding for PACT comes to an end, it is clear
      that much work remains to be done in the region. "Continuing clinical education"
      is only one part of a continuum of human resources for health (HRH) workforce
      development. Continued USAPI regional, U.S. national and international
      collaboration and resources are needed to achieve the ultimate goal of improved
      health and health care delivery in the USAPI.

PMID- 19772164
TI  - The Yap AHEC: an update 2002-2006.
AB  - The Yap Area Health Education Center (AHEC) is one of three U.S. Health Resources
      and Services Administration-funded AHEC programs in the U.S.-Affiliated Pacific
      Island jurisdictions (together with those in Palau and the Commonwealth of the
      Northern Mariana Islands). The Pacific Island AHECs are administered through the
      University of Hawai'i, John A. Burns School of Medicine and were founded in
      response to recommendations for development of the local health workforce by the
      U.S. Institute of Medicine in its 1998 report, "Pacific Partnerships for Health".
      The goal of the Yap AHEC is to build human capacity in the health workforce, and
      thereby strengthen the health service and improve health status for the people of
      Yap State. An ancillary goal is to pilot test new approaches to health workforce
      development, which might be shared with others in the region. These goals have
      been pursued by building partnerships with colleges in the region, with the new
      Wa'ab Community Health Center project in Yap and the Yap State Department of
      Health Services to bring formal college programs for students and health service
      staff to Yap State. To date, formal relationships have been established with five
      colleges; Palau Community College (PCC), the College of Micronesia-Federated
      States of Micronesia (FSM), Fiji School of Medicine (Department of Public Health
      & Primary Care), University of Hawai'i, Hilo, and the University of Alaska,
      Anchorage. A total of 143 students have been enrolled in 48 courses in several
      health worker disciplines, including clinical nurses, health assistant/dispensary
      managers, community health outreach workers, public health program staff pharmacy
      technicians and x-ray technicians. In addition to facilitating the delivery of
      courses in Yap, a new 6-course certificate program has been developed for
      community outreach workers in collaboration with the College of Micronesia, FSM
      and the Wa'ab Community Health Center (Wa'ab CHC) in order to support the CHC's
      innovative health service delivery model. The Yap AHEC has also assisted the
      College of Micronesia-FSM in the World Health Organization sponsored development
      of a proposal for the establishment of a nursing program, which is based on the
      decentralized, on-site (DC-OS) nursing training model that has been pilot tested
      in partnership with PCC at Yap State Hospital.

PMID- 19772165
TI  - A cross-sectional evaluation of the health dispensaries, community health, and
      current techniques for improving health assistant education on the outer islands
      of Yap State, Federated States of Micronesia.

PMID- 19772166
TI  - Dental manpower development in the Pacific: case study in the Republic of the
      Marshall Islands.
AB  - This case study reports the ongoing progress and results of a manpower
      development program to expand indigenous dental personnel at four levels in the
      Republic of the Marshall Islands. The program was designed to: 1) increase the
      number of Marshallese students who successfully complete dentistry training; 2)
      recruit and train a group of Marshallese high school graduates in dental
      assisting for service in new preventive outreach programs within the community;
      3) enhance the dental training of health assistants providing primary medical
      care to outer islands away from the main population centers of Majuro and Ebeye;
      and 4) provide in-service training on tooth decay prevention for Head Start
      teachers. The program resulted in the training of one Marshallese dentist and two
      Marshallese dental therapist, 16 primary care health aides who received oral
      health training for work in the outer island dispensaries, and 200 Head Start and
      kindergarten teachers who completed in-service training in oral health.
      Additional expertise was shared with other United States Affiliated Pacific
      Islands (USAPI) to enhance the dental workforce throughout the Pacific.

PMID- 19772167
TI  - Brief report on oral health prevention training in Yap State, FSM.

PMID- 19772168
TI  - Health problems of Micronesian patients at a student-run free homeless clinic.
AB  - BACKGROUND: As of November 2006, 41.3% of the residents at a newly established
      transitional homeless shelter in Hawai'i were of Micronesian descent. A student
      run medical clinic operates at this shelter every week. This study examines the
      medical problems found in the Micronesian patients at this clinic. METHODS: A
      retrospective chart review of 213 patients was conducted. Data was compiled from
      registration forms, intake forms, and progress notes. RESULTS: The most common
      medical conditions that patients reported having were musculoskeletal problems,
      hypertension, and diabetes. For actual patient encounters, health maintenance
      visits and acute conditions, such as upper respiratory infections, were the most
      frequent. CONCLUSIONS: Homeless Micronesian patients seen at this shelter
      presented with problems more similar to the general homeless population than for
      chronic conditions commonly cared for by providers of care to Micronesians in the
      community. More information about the health and other needs of homeless
      Micronesians in Hawai'i is warranted.

PMID- 19772169
TI  - Specificity of fetal tricuspid regurgitation in prediction of Down syndrome in
      Thai fetuses at 17-23 weeks of gestation.
AB  - OBJECTIVE: To assess the specificity of tricuspid regurgitation (TR) in
      prediction of Down syndrome in Thai fetuses at 17-23 weeks' gestation and to
      determine the prevalence of TR among normal chromosome fetuses in a high-risk
      population. MATERIAL AND METHOD: A prospective study was performed in 395 high
      risk pregnant women who underwent amniocentesis or cordocentesis for fetal
      karyotyping at 17-23 weeks. The presence or absence of TR was determined by
      pulsed wave Doppler at the time of prenatal diagnosis. TR was diagnosed when the
      regurgitation flow was observed for at least half of systole or > or = 70
      milliseconds with maximum velocity of > or = 100 cm/sec. The diagnostic values of
      TR for detection of Down syndrome were calculated. RESULTS: The prevalence of TR
      was 3.8% (14/370) in normal chromosome fetuses and 40% (2/5) in Down syndrome
      fetuses. Fetuses with TR had a higher chance to be Down syndrome (11.1%) than
      those without TR (0.8%) (95% CI of the difference, 0.09-32.9, p = 0.036).
      Specificity, sensitivity, NPV and PPV of TR in prediction of Down syndrome were
      95.9%, 40%, 99.2% and 11.1%, respectively. Among normal chromosome fetuses with
      TR, 14.3% (2/14) had congenital cardiac abnormalities. CONCLUSION: TR is not only
      a high specificity secondary ultrasound marker at 17-23 weeks to identify fetuses
      with Down syndrome in high-risk pregnant women but also associates with the risk
      of cardiac defects in normal chromosome fetuses.

PMID- 19772170
TI  - A survey study of etiology of altered consciousness in the emergency department.
AB  - BACKGROUND: Altered consciousness (AC) is a common presenting problem in the
      Emergency Department (ED), the causes of which can be either intracranial or
      extracranial in origin. OBJECTIVE: To determine the common etiologies of AC among
      patients in the ED of a medical teaching hospital and to build up a proper
      differential diagnosis. MATERIAL AND METHOD: A retrospective review of the
      medical records of patients who presented with AC in the ED between January and
      August 2004 was conducted Patient characteristics and demographic data as well as
      the etiologies of AC were presented in descriptive pattern. RESULTS: There were
      350 patients, of whom 67 (19.1%) were admitted, 38(10.9%) were transferred to
      other hospitals due to full occupancy, 35 (10%) died in the ED, and the rest
      (60%) were discharged and re-evaluated The mean age was 60.3 years old with 57.1%
      males and 42.9% females. The etiologies included neurological disorders (29.1%),
      endocrine/metabolic derangement (20.8%), infectious diseases and sepsis (18.8%),
      cardiovascular disorders (10%), psychiatric illness (8.8%), pulmonary (7.1%), and
      toxicological causes (5.1%). CONCLUSION: Though neurological disorders or
      intracranial causes were the most common etiology of AC in the ED, they accounted
      for only one-third of all cases in the ED. The larger proportion of AC cases was
      extracranial abnormalities including adverse effects from current medications.

PMID- 19772171
TI  - Correlation of epidermal growth factor receptor mutation, immunohistochemistry,
      and fluorescence in situ hybridization in esophageal squamous cell carcinoma.
AB  - BACKGROUND: The epidermal growth factor receptor (EGFR) has become a promising
      target for novel anticancer therapy Evaluation of its biological profiles
      including gene mutation, amplification, and protein expression in esophageal
      squamous cell carcinoma (ESCC) is essential to establish the EGFR molecular
      feature(s) suitable to select patients in anti-EGFR therapy. MATERIAL AND METHOD:
      The subjects' specimens of ESCC at Songklanagarind Hospital were obtained and
      investigated for EGFR protein expression and gene amplification. Polymerase chain
      reaction (PCR) was performed to amplify the EGFR DNA product. The mutational
      status of EGFR exons 19 and 21 was analyzed using direct sequencing. The entire
      biological profiles of the EGFR were then correlated. RESULTS: There were 48
      eligible ESCC specimens. No somatic mutation in the tyrosine kinase domain of
      EGFR was detected A high level of EGFR protein was exhibited in 22 patients
      (46%). Twenty-three patients (48%) had shown a high gene copy numbers. However,
      no direct correlation between EGFR protein and gene status was observed.
      CONCLUSION: EGFR mutations in the tyrosine kinase domain of exons 19 and 21 were
      absent in ESCC, whereas, protein overexpression and gene amplification was
      prevalent. Therefore, selection of ESCC patients for studies with anti-EGFR
      agents based on protein expression or gene copy number, not gene mutation, is
      rational.

PMID- 19772172
TI  - Long-term outcomes of de novo acute myeloid leukemia in Thai patients.
AB  - BACKGROUND: Acute myeloid leukemia (AML) is the heterogeneous disease. As per
      previous reports, there are some differences in clinical features and cytogenetic
      biomarkers of AML among different ethnic backgrounds. Therefore, we conducted a
      retrospective study to analyze clinical outcomes and predictive factors of Thai
      AML patients receiving chemotherapy treatment. MATERIAL AND METHOD: The authors
      performed a retrospective analysis of 106 adults with newly diagnosed de novo AML
      at Ramathibodi Hospital between 2003 and 2007. Of 101 patients with non- M3
      subtype, the patients received induction and consolidation chemotherapy with
      anthracyclin plus cytarabine based regimens (3 + 7). All patients achieving
      complete remission (CR) were treated with intensive chemotherapy using
      intermediate dose cytarabine plus anthracyclin based protocol. All patients with
      M3 subtype, the induction chemotherapy consisted of a combination of all-trans
      retinoic acid (ATRA) and anthracyclin. All patients achieving complete remission
      (CR) were treated with three courses of mitoxantrone as consolidation
      chemotherapy, followed by maintenance chemotherapy with methotrexate, etoposide
      and ATRA. RESULTS: Of the 106 patients, median age was 43.5 years (15-73 years)
      and 19 (17.9%) were older than 60 years. Fifty-six patients (52.8%) were female.
      Common subtypes were M4 (28.3%), M1 (26.4%) and M2 (20.8%). Of the 95 patients
      who were performed with cytogenetic analysis, 55 (58%) had abnormal karyotype.
      AML with recurrent cytogenetic translocations, complex chromosome, trisomy 8,
      polyploidy, del 5q and del 7q were found in 16.8, 6.3, 5.3, 5.3, 2.1 and 3.2%,
      respectively. Most patients (70.5%) had intermediate-risk cytogenesis. Eighty
      patients (75.5%) were treated with idarubicin and cytarabine induction regimen.
      Of the 96 evaluable patients, 60 (62.5%) achieved complete remission (CR), 38
      (39.6%) with the first course of chemotherapy. Median time to CR was 54 days (25
      168 days). The CR rate was 78.6% for the good-risk cytogenetic group, 67.2% for
      the intermediate- risk cytogenetic group, and 37.5% for the poor-risk cytogenetic
      group. Median follow-up time was 10.4 months, 5-year-DFS and 5-year-OS were 41
      and 22.2%, respectively. Patients with poor-risk cytogenetic factors had
      significantly lower CR rate (p = 0.021). The CR status significantly predicted OS
      (p < 0.001). CONCLUSION: The overall complete remission rate of Thai AML patients
      is in 60%. Only a small proportion of the presented patients have long-term DFS
      and OS, the significant factor for predicting survival of Thai AML patients is
      the complete remission status. Poor-risk cytogenetic factors are associated with
      poor treatment outcomes.

PMID- 19772173
TI  - The mechanism of increased vascular permeability in renal ischemic reperfusion
      injury: potential role of angiopoietin-1 and hyaluronan.
AB  - BACKGROUND: One striking feature observed during renal ischemia reperfusion
      injury (IRI) is the increase in interstitial fluid and infiltration, which
      reflects an increase in vascular permeability. Angiopoietin-1 (Ang-1) prevents
      vascular leakage and inflammation. Hyaluronic acid (HA) has a high capacity to
      bind and retain water and is pro-inflammatory factor. MATERIAL AND METHOD: The
      authors evaluated the expression of Ang-1 and HA during renal IRI bilaterally for
      30 minutes. Renal tissue was sent for pathologic study, proteins expression, and
      mRNA in renal IRI at 24 and 48 hr. RESULTS: At 24 hr post-injury, histopathology
      studies revealed severe tubular epithelial cell (TEC) necrosis, peritubular
      capillary (PTC) congestion, mild interstitial infiltration, and edema.
      Histopathology at 48 hr post-injury showed a progressive increased degree of PTC
      congestion, interstitial infiltration and edema. In normal kidney, Ang-1 was
      abundant in glomerulus and PTC patterns, while HA is absent in the cortex but
      present in the medulla. At 24 and 48 h rpost-IRI, kidney cortex and medulla
      showed a reduced Ang-1 staining but with an increase in HA staining. Western blot
      analysis showed that levels of Ang-1 expression decreased to 44% of normal levels
      at 24 hr post-IRI and further declined to 31% at 48 hr post-IRI. Using real time
      RT-PCR, Ang-1 expression declined to 15% of normal levels at 24 hr post-IRI and
      sustained at 48 hr post-IRI. CONCLUSION: These results suggest that lowered Ang-1
      expression levels and increased HA may contribute to an increased permeability
      and inflammation of microcirculation in renal IRI.

PMID- 19772174
TI  - Validity and reliability of CHOICE Health Experience Questionnaire: Thai version.
AB  - OBJECTIVE: Assess the reliability and validity of the Thai translation of the
      CHOICE Health Experience Questionnaire (CHEQ), which is the English-language
      questionnaire, developed specifically for End-stage-renal disease (ESRD)
      patients. The CHEQ comprised of two parts, nine general domains of SF-36
      (physical function, role-physical, bodily pain, mental health, role-emotional,
      social function, vitality, general health, and report transition) and 16 dialysis
      specific domains of the CHEQ (role-physical, mental health, general health,
      freedom, travel restriction, cognitive function, financial function, restriction
      diet and fluids, recreation, work, body image, symptoms, sex, sleep, access, and
      quality of life). MATERIAL AND METHOD: The authors translated the CHEQ
      questionnaire into Thai and confirmed the accuracy by back translation. Pilot
      study sample was 10 Thai ESRD patients. Then the CHEQ (Thai) was applied to 110
      Thai ESRD patients. Twenty-three patients had chronic peritoneal dialysis
      patients and 87 were chronic intermittent hemodialysis patients. Statistical
      analysis included descriptive statistics, Mann-Whitney U test, Student's t-test,
      and Cronbach's alpha. RESULTS: Construct validity was satisfactory with the
      significant difference less than 0.001 between the low and high group. The
      reliability coefficient for the Cronbach's alpha of the total scale of the CHEQ
      (Thai) was 0.98. The Cronbach 's alphas were greater than 0.7 for all domains,
      range from 0.58 to 0.92, except the social function and quality of life domain
      (alpha = 0.66 and 0.575). CONCLUSION: The CHEQ (Thai) is reliable and valid for
      assessment of Thai ESRD patients receiving chronic dialysis. Its properties are
      similar to those reported in the original version.

PMID- 19772175
TI  - Efficacy and safety of parenteral amoxycillin/ clavulanate for prevention of
      surgical site infection following abdominal surgery.
AB  - OBJECTIVE: The aim of the present study was to evaluate the efficacy and safety
      of parenteral amoxycillin/ clavulanate for the prevention of surgical site
      infection (SSI) following intra-abdominal surgery. MATERIAL AND METHOD: This
      prospective opened non-comparative clinical trial was conducted in the Department
      of Surgery, Faculty of Medicine Siriraj Hospital, Bangkok, Thailand between 1
      April 2004 and 30 September 2004. Prophylactic amoxycillin/clavulanate (Cavumox)
      at a dose of 1.2 gram was given intravenously to all patients who underwent
      emergency or elective intra-abdominal procedures. All patients were scheduled to
      follow-up visits at 7, 14 and 30 days post operatively for monitoring the
      occurrence of SSI. RESULTS: Thirty emergency appendectomies (85.7%) and other 5
      elective surgical procedures (14.3%) were performed in 35 patients including 14
      males and 21 females with a mean age of 37 (range, 18-72) years. No SSI or drug
      allergy was observed. CONCLUSION: Parenteral amoxycillin/clavulanate is a safe
      and effective antibiotic as the monotherapy for prevention of SSI following intra
      abdominal surgery.

PMID- 19772176
TI  - N-acetylcysteine inhibits proliferation, adhesion, migration and invasion of
      human bladder cancer cells.
AB  - OBJECTIVE: Bladder cancer is not only a major public health and economically
      burden for the patients but also a major clinical impact for Thai urologists. The
      authors' aim was to study the anti-metastatic effect of N-acetylcysteine (NAC),
      one of the cheap, safe and widely used over-the-counter-drugs in Thailand, on the
      human bladder cancer cells. MATERIAL AND METHOD: Effects of NAC at various
      concentrations on the growth, adhesion, migration, and invasion of the human
      bladder cancer cell line were assessed in vitro. RESULTS: NAC at the
      concentrations of 5, 10, 20 and 30 mM could directly and significantly inhibit
      the growth, adhesion, migration, and invasion of the human bladder cancer cells
      in a dose-dependent manner The 50% inhibitory concentration (IC50) value for cell
      viability was 33.33 +/- 0.78 mM. The inhibitory effects on migration, invasion
      and adhesion properties of the cancer cells were dramatically observed at the
      concentrations of > or = 10, > or = 20 and > or = 30 mM respectively. CONCLUSION:
      NAC has an anti-metastatic effect on the human bladder cancer cells by inhibiting
      their growth, adhesion, migration, and invasion properties. This implies the high
      possibility that the urologists may apply the results to use it intravesically
      before, during and after the transurethral resection of bladder tumour in
      addition to its conventional usage by oral and parenteral routes.

PMID- 19772177
TI  - Plasma glucose level in elective surgical patients administered with 5% dextrose
      in 0.45% NaCl in comparison with those receiving lactated Ringer's solution.
AB  - OBJECTIVE: To determine the effect of dextrose containing solution (5% dextrose
      in 0.45% NaCl) compared to non-dextrose containing solution (lactated Ringer's
      solution) on plasma glucose level in elective surgical patients. MATERIAL AND
      METHOD: A prospective randomized double-blind control trial was conducted on 60
      patients aged 18-60, with ASA physical status I to II, who were scheduled for
      elective surgery at Maharaj Nakorn Chiang Mai Hospital, Thailand between October;
      2007 and September; 2008. The patients received either lactated Ringer's solution
      (Group L), or 5% dextrose in 0.45% NaCl (Group D) in the morning of the operation
      day. Blood glucose levels were determined before intravenous fluid administration
      (T0), at the beginning (T1), after the 1st hr (T2), and at the end of surgery
      (T3). RESULTS: Mean duration of preoperative fast was almost 11 hrs in both
      groups; however, none of the patients had preoperative hypoglycemia. The blood
      sugar levels were significantly higher in the patients receiving 5% dextrose
      solution compared to the patients receiving lactated Ringer's solution at the
      beginning, after the 1st hr and at the end of surgery (p-value = 0.06, 0.018 and
      0.036 respectively). There were some patients having hyperglycemia after
      receiving 5% dextrose in 0.45% NaCl during surgery. However, none of the average
      plasma glucose values in either group was considered as hyperglycemia.
      CONCLUSION: Though they fasted many hours before surgery, no patients were found
      to have hypoglycemia. The large volume of lactate Ringer's solution had minimal
      effect on the blood sugar levels compared to the levels in 5% dextrose in 0.45%
      NaCl group. Therefore, lactate Ringer's solution is probably the alternative
      choice of intravenous fluid for perioperative maintenance and can be used as
      replacement in healthy patients undergoing elective surgery.

PMID- 19772178
TI  - Profile Soft-Seal Cuff for general anesthesia under ambulatory gynecologic
      laparoscopy.
AB  - OBJECTIVE: To compare the severity of throat discomfort in terms of sore throat,
      dysphagia, and dysphonia caused by LMA-ProSeal (PLMA) and Profile Soft-Seal Cuff
      (PSSC) in early (2 hour) and late (24 hour) postoperative period after ambulatory
      gynecologic laparoscopy. DESIGN: Randomized double-blind controlled trial.
      MATERIAL AND METHOD: One hundred and thirty eight patients undergoing ambulatory
      gynecologic laparoscopy in Chulalongkorn Memorial Hospital were randomly
      allocated into two groups. One group was intubated with Profile-Soft-Seal Cuff
      (PSSC), while the other with ProSeal LMA (PLMA). Four-leveled score of sore
      throat, dysphagia, dysphonia, nausea, or vomiting symptoms at 2 and 24 hours and
      5-leveled satisfaction score to both techniques at 24 hours postoperatively were
      evaluated. RESULTS: The patients in the PLMA group had less severe symptoms of
      sore throat (p = 0.016) and dysphonia (p = 0.003) than those in the PSSC group at
      2 hour. No difference was detected for dysphagia, nausea, vomiting, and
      satisfaction scores at 24 hour postoperatively. CONCLUSION: PLMA caused less sore
      throat and dysphonia in the early postoperative period than PSSC did PLMA can be
      used as an alternative airway device for anesthesia in ambulatory gynecologic
      laparoscopy.

PMID- 19772179
TI  - Three-dimensional morphometric study of the Thai proximal humerus: cadaveric
      study.
AB  - Seventy-six cadaveric humeri were investigated to study the three-dimensional
      morphometric data based on CT data. The present study was an advanced method to
      determine the 3D proximal humeral parameters for both intra and extra geometries
      through the utilization of medical imaging and reverse engineering techniques.
      The following parameters were calculated for each humerus and then compared with
      the 3D Caucasian data such as diameter of humeral head, articular surface
      thickness, inclination angle, retroversion angle, medial offset, posterior
      offset, curve length, radius of curvature, and mediolateral angle. It was found
      that the Thai humeral parameters were smaller than Caucasian except the
      retroversion angle and posterior offset. This data could be further used to
      develop a proper design of shoulder arthroplasty for Thai patients.

PMID- 19772180
TI  - Clinical evaluation of intra-bleb pigmentation after trabeculectomy: a case
      control study.
AB  - OBJECTIVE: To evaluate the clinical status of a filtering bleb with visible
      pigment (intra-bleb pigmentation, IBP), in a case-controlled manner. MATERIAL AND
      METHOD: Forty-one patients with IBP and 40 patients without visible pigment in
      blebs (controls) were enrolled from the authors' clinic. All patients underwent
      either trabeculectomy alone or combined cataract extraction with intraocular lens
      implantation and trabeculectomy. RESULTS: Mean follow-up period was 22.8 months.
      Complete success (final IOP < 22 mmHg without additional treatment) was achieved
      more often in IBP patients (82.9%) than in controls (60%, p = 0.022). Median
      survival time was greater in IBP patients (49.9 +/- 0 months) than in controls
      (35.5 +/- 4.9 months, p = 0.013). Regression analysis revealed that IBP was
      associated with thin and cystic blebs (p = 0.023). Sex, age, eye, diagnosis,
      procedure, and mitomycin C had no effect on IBP development. IBP grading,
      location, and appearance did not relate to the success rate or bleb
      characteristics. CONCLUSION: IBP appears to be a favorable sign in filtering
      blebs, in terms of complete success and survival time, because IBP is associated
      with thin-walled blebs. Clinicians should carefully observe patients for IBP when
      evaluating filtering blebs.

PMID- 19772181
TI  - Effect of rebamipide on gastric ulcer healing caused by Helicobacter pylori
      and/or NSAIDs or non NSAIDs-non H. pylori.
AB  - BACKGROUND: Rebamipide, a gastro-protective drug, acts on stimulation of
      prostaglandin and mucus glycoprotein synthesis, inhibition of reactive oxygen
      species, inflammatory cytokines, and neutrophils activation. OBJECTIVE: To
      investigate the effect of rebamipide (mucosta) on healing of gastric ulcer caused
      by various etiologies. MATERIAL AND METHOD: Thirty patients with gastric ulcer
      underwent gastric antral and body biopsies for histopathology. Group
      classifications depended on H. pylori status using CLO test, histology or urea
      breath test and history ofNSAIDs taking. All patients received rebamipide 100 mg,
      three times a day, for 8 weeks. The symptoms and adverse effects were assessed in
      4 weeks and 8 weeks after prescription. At the end of the present study, an
      endoscopy was repeated to evaluate ulcer healing and biopsy for gastric
      inflammation grading. RESULTS: According to the ulcer cause, there were seven
      patients with H. pylori+ NSAIDs+, nine patients with H. pylori + NSAIDs-, three
      patients with H. pylori - NSAIDs +, and 11 patients with H. pylori - NSAIDs-. The
      ulcers were completely healed in most patients with a history of NSAIDs use.
      There was a significant improvement of symptom scores from baseline in all groups
      (5.9 vs. 0.6, p < 0.001). The improvement of gastric inflammation scores were
      favorable in NSAIDs users (2.38 vs. 1.75, p = 0.011). All patients were satisfied
      as there were few adverse effects. CONCLUSION: Rebamipide is effective and well
      tolerated for treatment of gastric ulcers especially those caused by NSAIDs, as
      it promotes the improvement of gastric inflammation scores, clinical symptoms,
      and ulcer healing.

PMID- 19772182
TI  - Gastrointestinal stromal tumor: computed tomographic features.
AB  - OBJECTIVE: To describe anatomical distribution and CT findings of
      gastrointestinal stromal tumors in Srinagarind Hospital. MATERIAL AND METHOD: The
      abdominal CT images of 16 patients (12 men, 4 women: mean age 49 +/- 17SD) with
      pathologically proven GISTs during 1998-2005 were retrospectively reviewed. The
      tumor sites, sizes, borders, growth patterns, patterns of enhancement, and sign
      of malignancy were evaluated. The findings of benign and malignant GISTs were
      compared. RESULTS: Among sixteen patients, the most common location of GISTs was
      stomach (56.25%). The others were small bowel (43.75%), and tumor size larger
      than 5 cm. The present study found that the smooth and mixed smooth and irregular
      surface lesions are equal in number (50%). The growth was extraluminal in 56.25%.
      Almost all tumors had inhomogeneous density (n = 15). Intratumoral gas (43.75%),
      fluid (37.5%), and calcification (50.00%), were present in the tumors. All cases
      showed inhomogeneous contrast enhancement. The CT signs of malignancy found were
      invasion of the adjacent organ(s) (62.5%), lymphadenopathy (25%), liver
      metastasis/nodule (18.75%), ascites (6.25%), perilesional fat plane stranding
      (93.75%), and pleural effusion (6.25%). CONCLUSION: The most common site of GISTs
      is the stomach. The typical tumors appear as inhomogeneous enhancing
      inhomogeneous extraluminal mass with either well-defined or irregular border. The
      CT findings cannot be used as a single tool for differentiating the benign from
      malignant GISTs.

PMID- 19772183
TI  - Xerostomia, hyposalivation, and oral microbiota in type 2 diabetic patients: a
      preliminary study.
AB  - BACKGROUND AND OBJECTIVE: Mouth dryness is one of the major problems that can
      lead to several oral diseases such as dental caries, periodontitis and oral
      infection. Mouth dryness has also been associated with type 2 diabetes mellitus
      (DM). The objective of the present study was to investigate the prevalence of
      xerostomia (feeling of mouth dryness), hyposalivation (the reduction of saliva),
      and oral microbiota in Thai patients with type 2 DM. MATERIAL AND METHOD: One
      hundred and fifty-four ambulatory patients with type 2 DM and 50 non-diabetic
      control subjects were interviewed for symptoms of xerostomia. The medical records
      of these subjects were reviewed for pertinent medical history and laboratory
      investigations regarding their diabetic control. Oral examination and measurement
      of hyposalivation using a modified Schirmer test (MST) were performed The
      presence of oral microbial flora was investigated using a modified dip-slide
      test. RESULTS: The prevalence of xerostomia was 62% in patients with type 2 DM
      compared with 36% in the nondiabetic control group (p = 0.001). The prevalence of
      hyposalivation (defined as MST values < or = 25 mm at 3 min) was 46% in the
      patient group, whereas only 28% of the control group had hyposalivation (p =
      0.03). Patients with hyposalivation had significantly higher numbers of mutans
      streptococci, Lactobacillus spp., and Candida spp. in the saliva compared with
      those without hyposalivation. CONCLUSION: These results suggested that xerostomia
      and hyposalivation were prevalent in patients with type 2 DM and were associated
      with higher numbers of oral pathogens in the saliva.

PMID- 19772184
TI  - Bioequivalence study of 50 mg sertraline tablets in healthy Thai volunteers.
AB  - OBJECTIVE: To determine the bioavailability of 50 mg sertraline tablets between
      the test product (Zotaline, M&H Manufacturing Co., Ltd, Thailand) and the
      reference product (Zoloft, Pfizer Australia Pty Ltd, Australia). MATERIAL AND
      METHOD: An open-labeled, single dose, 2-treatment, 2-period, 2-sequence,
      randomized crossover study under fasting conditions with 14 days washout period
      was conducted in 24 healthy Thai volunteers. Blood samples were collected before
      dosing and at frequent intervals for up to 96 h post dose. Analysis of sertraline
      concentrations was performed using a validated liquid chromatography with tandem
      mass spectrometry (LC-MS/MS) method. RESULTS: Twenty-four volunteers completed
      both treatment periods. Pharmacokinetic parameters were determined using the non
      compartment model. The 90 percent confidence intervals of the geometric mean
      ratios (test/reference) of C(max) 104.47% (96.64%-112.93%), AUC(0-96) 108.06%
      (100.71%-115.94%) and AUC(0-infinity) 108.39% (100.93%-116.40%) fell within the
      equivalence range (80%-125%). There was no significant difference of the T(max)
      parameter between the two formulations (p > 0.05). No serious adverse events
      related to the study drugs were found. CONCLUSION: The two formulations of
      sertraline tablets were bio-equivalent in Thai healthy volunteers.

PMID- 19772185
TI  - Bioequivalence study of 500 mg glucosamine sulfate in Thai healthy volunteers.
AB  - BACKGROUND AND OBJECTIVE: Glucosamine sulfate is widely used to relieve symptoms
      from osteoarthritis. The present study was conducted in order to determine
      pharmacokinetic and assess the in-vivo bioequivalence of two different hard
      capsule formulations of glucosamine sulfate when administered as equal dose of
      500 mg. The two formulations contained different salt form where reference
      product is NaCl and test product is KCl. MATERIAL AND METHOD: A randomized,
      single dose, two-treatment, two-period, two-sequence crossover study was
      conducted. Twenty-four healthy volunteers were recruited at Siriraj Clinical
      Research Unit. Each subject received a dose of 500 mg glucosamine sulfate of both
      formulations with at least one-week washout period. Blood samples were collected
      over 24 h after the oral administration. The plasma fractions were analyzed for
      glucosamine using a liquid chromatography-mass spectrometry (LC-MS/MS). RESULTS:
      Twenty-four volunteers were enrolled in the present study Pharmacokinetic
      parameters were determined using the non-compartment model. The 90% confidence
      intervals of the mean ratios (test/reference) of C(max) (93.69%; ranged from
      86.68%-113.32%) and AUC(0-t), (97.73; ranged from 87.38%-112.62%) fell within the
      acceptable range (80-125%) for bioequivalent eligibility. Both preparations were
      well tolerated and had a few non-serious adverse events. CONCLUSION: The
      glucosamine sulfate containing KCl (test product) is bioequivalent to glucosamine
      sulfate containing NaCl (reference product) in terms of rate and extent of
      absorption.

PMID- 19772186
TI  - Role of stress areas, stress severity, and stressful life events on the onset of
      depressive disorder: a case-control study.
AB  - BACKGROUND: Although the stress and stressful life events are known as the
      precipitation of depressive disorder, the areas of stress and types of stressful
      life events found in depression are varied by different socio-cultural context.
      OBJECTIVE: Identify the stress areas, stress severity, and types of stressful
      life events associated with the onset of depressive disorder in Thai depressed
      patients. MATERIAL AND METHOD: Ninety depressed and ninety non-depressed
      subjects, aged above 18 years old, from the Department of Psychiatry, King
      Chulalongkorn Memorial Hospital, were recruited into the present study between
      July 2007 and January 2008. All subjects completed a demographic data form, and a
      1-Year Life Stress Event Questionnaire. The association between the number of
      stressful life events, stress areas, stress severity, types of stressful life
      events, and the onset of depressive disorder were analyzed by independent t-test
      and chi-square test. Logistic regression was performed to identify the predictors
      of depressive disorder. RESULTS: Most of the subjects were young and middle-aged
      women, living in Bangkok and the central region. The depressed subjects
      experienced more stressful life events than the non-depressed subjects (5.81 +/-
      3.19 vs. 3.24 +/- 2.80 events in one year) (p < 0.01). All stress areas (health
      related, family-related, financial, occupational, and social stress), and overall
      stress were associated with the onset of depressive disorder (p < 0.05). Subjects
      with the moderate-to-severe stress in all areas were at the higher risk of
      depressive disorder than those with the mild stress (p < 0.05). Health-related
      stress was the stress area highest associated with the depressive disorder (OR =
      5.93, 95% CI = 2.33-16.92, p < 0.01). The types of stressful life events
      associated with the onset of depressive disorder were the medical
      hospitalization, medical illness leading to missing work or disturbed daily
      routine, change in sleeping habits, absence of recreation, arguments with spouse,
      sexual difficulties with spouse, family financial problems, job loss, and trouble
      with boss (p < 0.05). The logistic regression showed that the moderate-to-severe
      stress was the significant predictor of depressive disorder (adjusted OR = 5.26,
      95% CI = 1.85-14.92, p < 0.01). CONCLUSION: Stress areas, stress severity, and
      stressful life events had the impact on the onset of depressive disorder in Thai
      depressed patients. The important stressful life events in Thai depressed
      patients included severe medical illness, job loss, financial distress, and
      relationship problems.

PMID- 19772187
TI  - Expression of hormonal receptor in patients with metastasizing pleomorphic
      adenoma of the major salivary gland; a clinicopathological report of three cases.
AB  - BACKGROUND: Metastasizing pleomorphic adenoma is an uncommon malignant tumor of
      the salivary gland demonstrating benign epithelial and modified myoepithelial
      elements intermingling with tissue of mucoid, myxoid, or chondroid appearance
      that inexplicably manifests local or distant metastasis. OBJECTIVE: To determine
      the expression of hormonal receptor in the patients with metastasizing
      pleomorphic adenoma of the major salivary gland. MATERIAL AND METHOD: Medical
      records, clinical and pathologic findings of three patients who were diagnosed as
      metastasizing pleomorphic adenoma were reviewed. The immunohistochemical stains
      for estrogen receptor, progesterone receptor, and Ki-67 were performed. RESULTS:
      Three cases of metastasizing pleomorphic adenoma, clinically presenting as
      painless, gradually enlarged cervical lymph nodes were reported. The pathologic
      examinations of the cervical lymph nodes are morphologically and
      immunohistologically identical to the sialoadenectomy specimen.
      Immunohistochemical stains show positive reactivity to progesterone receptor but
      negative reactivity to estrogen receptor in both mesenchymal and epithelial
      components of pleomorphic adenoma. CONCLUSION: These are the first reported cases
      of metastasizing pleomorphic adenoma of the major salivary glands associated with
      expression of progesterone receptor in both specimens of sialoadenectomy and
      lymph node biopsy. This finding supports the pathogenesis of benign metastasis of
      tumor. However, the role of hormonal receptor in the pathogenesis and treatment
      of salivary metastasizing pleomorphic adenoma should be further investigated.

PMID- 19772188
TI  - Down syndrome parents' support group in Thailand Siriraj Hospital, fifteen years
      experience: a review.
AB  - Down Syndrome Parents' Support Group Siriraj Hospital was established on February
      14, 1993. It consists of a group of pediatricians, nurses, parents of children
      with Down Syndrome (DS) who received care at the Genetics Clinic, Division of
      Medical Genetics, Department of Pediatrics, Faculty of Medicine Siriraj Hospital.
      The objective is to educate parents with DS children whose diagnosis of DS given
      at birth causing grief and disappointment which led to abandonment of these
      children at Siriraj Hospital almost every other month (fifteen years ago) due to
      lack of education on the part of the medical professionals. Down Syndrome
      Parents' Support Group Siriraj Hospital received financial support from Terres
      des hommes of the Netherlands in the first 6 years. Later it received partial
      financial support from a government agency; however, the majority of the funding
      came from private donations. Throughout the years, the group had several
      successful activities: Siriraj Down Syndrome Annual Meeting since 1991 (total of
      17 years) and Down Syndrome Provincial Lecture tour, so called "Down Sunjorn"
      since 1997. The latest in 2008 (the tenth) which was organized with major
      provincial hospitals of the Ministry of Public Health (MOPH). Moreover the group
      took part in (1) working with the Ministry of Education for Thailand Educational
      Act B.E. 1999 which promotes integration of DS children into normal schools all
      over the country, (2) working with the Department of Maternal & Child Health,
      MOPH started the Child Development Center in the provincial community hospitals
      where the service was lacking; (3) working with Ministry of Social Development'
      and Human Security to initiate an educational program for the DS families in the
      rural areas (from 2001 - 2006) to help educate families with DS children and
      raise awareness for their educational & legal rights. In the past 15 years, there
      was no more abandonment of DS children at Siriraj Hospital and others; these
      children received better care and improved quality of life.

PMID- 19772190
TI  - Collaborating to bring new therapies to the patient--the TREAT-NMD model.

PMID- 19772189
TI  - Encephalomyopathies caused by abnormal nuclear-mitochondrial intergenomic cross
      talk.
AB  - Autosomal dominant Progressive External Ophthalmoplegias are Mendelian disorders
      characterized by the accumulation of multiple deletions of mitochondrial DNA in
      critical tissues. Most of the Autosomal dominant Progressive External
      Ophthalmoplegias families carry heterozygous mutations in one of three genes:
      ANT1, encoding the muscle-heart specific mitochondrial adenine nucleotide
      translocator, Twinkle, encoding the mitochondrial DNA helicase, and POLG1,
      encoding the catalytic subunit of the mitochondrial DNA-specific polymerase.
      Mutations in both POLG1 alleles are also found in autosomal recessive Progressive
      External Ophthalmoplegias sibships with multiple affected members and in
      apparently sporadic cases. In addition, recessive POLG1 mutations are responsible
      for three additional diseases: Alpers-Huttenlocher hepatopathic poliodystrophy,
      Sensory-Ataxic Neuropathy Dysarthria and Ophthalmoplegia and juvenile
      SpinoCerebellar Ataxia-Epilepsy syndrome. Mitochondrial neuro-gastro-intestinal
      encephalomyopathy is an autosomal recessive disorder of juvenile onset, caused by
      mutations in the gene encoding Thymidine Phosphorylase. Thymidine Phosphorylase
      is involved in the control and maintenance of the pyrimidine nucleoside pool of
      the cell. Finally, mitochondrial DNA depletion syndrome is a heterogeneous group
      of disorders characterized by a reduction in mitochondrial DNA copy number.
      Clinically, they include a myopathic form, a more generalized encephalomyopathic
      form and a fatal infantile hepato-cerebral syndrome leading to rapidly
      progressive liver and brain failure. To date, eight genes have been associated
      with mitochondrial DNA depletion syndrome. Novel disease genes have recently been
      added to this list, including OPA1 and GFER, and new clinical variants add
      further complexity to this expanding area of mitochondrial medicine.

PMID- 19772192
TI  - High frequency of Friedreich's ataxia carriers in the Paphos district of Cyprus.
AB  - A cluster of Friedreich's ataxia patients has been previously investigated in two
      neighbouring villages of the Paphos district of Cyprus. Molecular genetic studies
      revealed that all patients had the most common mutation, a homozygous expansion
      of the GAA triplet repeat in the first intron of the frataxin gene. The present
      study is aimed at estimating the mutation carrier frequency in the broader area
      of Paphos. Overall, 1050 individuals originating from the Paphos district took
      part in the programme. Blood samples were collected for a period of 18 months, on
      a voluntary basis, after signing a consent form, and analysis of the GAA triplet
      repeat was performed. The frequency of mutation carriers in the broader area of
      the Paphos district, and excluding the two neighbouring cluster villages, is
      estimated to be high. We recommend that an organized prevention programme be
      implemented to cover the population from this region.

PMID- 19772193
TI  - [What future for cardiovascular prevention trials?].

PMID- 19772191
TI  - Mitochondrial disorders of the nuclear genome.
AB  - BACKGROUND: Mitochondrial myopathies are regulated by two genomes: the nuclear
      DNA, and the mitochondrial DNA. While, so far, most studies have dealt with
      mitochondrial myopathies due to deletions or point mutations in the mitochondrial
      DNA, a new field of investigation is that of syndromes due to mutations in the
      nuclear DNA. These latter disorders have mendelian inheritance. RESULTS: Three
      representative cases have been selected: one with COX deficiency and a Leigh
      syndrome due to a SURF1 gene mutation, one due to a defect of Coenzyme Q
      synthesis and one with dominant optic atrophy due to a mutation in the OPA1 gene.
      CONCLUSIONS: Future developments will show that many neurodegenerative disorders
      are due to mutations of nuclear genes controlling mitochondrial function, fusion
      and fission.

PMID- 19772194
TI  - [Prevention of restenosis and of cardiac events after coronary angioplasty in
      diabetics].
AB  - Various systemic pharmacological approaches have been evaluated to reduce the
      risk of restenosis and clinical complications after coronary angioplasty, with or
      without stent, a main objective in the high risk diabetic population. The aim of
      the present paper is to describe the effects of the main pharmacological classes
      on the risk of restenosis, the need for new revascularisation procedures and the
      incidence of major clinical events (MACE: death, myocardial infarction,
      revascularisation). We will analyse successively the role of antiplatelet agents,
      omega 3 fatty acids, statins, anti-inflammatory compounds, immunomodulators, anti
      oxidants and inhibitors of the renin-angiotensin system. Whenever possible, we
      will focus our attention on the results obtained in the diabetic population.

PMID- 19772195
TI  - [Metabolically obese normal-weight individuals and metabolically healthy, but
      obese, subjects].
AB  - The relationships between body weight and metabolic abnormalities are not so
      simple. Indeed, there are metabolically obese normal-weight (MONW) individuals,
      who are frequently not detected because of a falsely reassuring body weight, and,
      in contrast, metabolically healthy, but obese, people (MHO). The different
      topography and hormonal-metabolic and pro-inflammatory activities of various
      adipose depots seem to play a major role to explain this paradox. The present
      review paper aims at describing the main principles of management of MONW
      individuals, with the objective to reduce the higher risk of type 2 diabetes and
      cardiovascular disease, and to discuss both the advantages and uncertainties of a
      classical weight-reducing approach in MHO people.

PMID- 19772196
TI  - [Management of Parkinson's disease in 2009].
AB  - The cause of Parkinson's disease remains unknown and no cure or prevention exists
      so far. Levodopa remains by far the most potent symptomatic therapy, but induces
      side-effects such as motor fluctuations and abnormal movements, which can
      somewhat be counterbalanced by optimizing levodopa plasma levels or acting at
      receptors level with long half-life dopamine agonists. In severe cases,
      functional surgery with deep brain stimulation can be offered. Some non
      dopaminergic symptoms like dementia, freezing, postural instability or
      dysautonomia do not respond to dopaminergic drugs and need special care.

PMID- 19772197
TI  - [Obsessive compulsive disorder (OCD)].
AB  - Obsessive compulsive disorder (OCD) is a frequent and disabling psychic illness.
      Along psychiatric history, several etiological models have been successively
      hypothesized to explain the obsessive compulsive symptoms from a psychological,
      behavioural or biological point of view. This review aims at presenting OCD
      etiological models as well as describing OCD clinical and therapeutic aspects.

PMID- 19772198
TI  - [Current treatment of follicular lymphoma].
AB  - After diffuse large B-cell lymphoma, follicular lymphoma is the most frequent non
      Hodgkin's lymphoma. It remains incurable, except for localized diseases. Advanced
      disease has to be treated only in the presence of clinical and/or biology
      aggressiveness. These patients should be treated by rituximab (Mab-Thera)
      associated to polychemotherapy comprising cyclophosphamide, vincristine and
      prednisone. After this therapy, the benefit of rituximab in maintenance has to be
      confirmed. Autologous stem cell transplantation is now reserved for young
      patients in first relapse. Allogenic stem cell transplantation is also an
      interesting option. The other therapeutic options comprise radio-immunotherapy
      with 90Y ibritumomab tiuxetan (Zevalin) and bortezomib (Velcade).

PMID- 19772199
TI  - [Paraneoplastic endocrine syndromes: diagnosis and management].
AB  - Paraneoplastic endocrine syndromes define a group of secondary signs and symptoms
      associated to a neoplasia, independently from the location of the primary tumor
      or its metastases. Paraneoplastic or ectopic endocrine syndromes usually result
      from aberrant hormone precursors or hormone-like substances by tumours. Knowledge
      of paraneoplastic endocrine complications is important both for the early
      diagnosis of neoplasia and the prognosis of the patient. In this review we
      discuss almost all reported paraneoplastic endocrine syndromes. We analyze their
      prevalence, etiology, laboratory diagnosis and treatment.

PMID- 19772200
TI  - [Really so far from fast-track colorectal surgery in senior patients?].
AB  - Senior population (> or = 70 y) represents approximately 17% of Western
      population and account for 2/3 of all solids cancers of which > 50% are
      colorectal. Their treatment would request major abdominal surgery, often not
      offered because of senior age or fear of prohibitive morbidity. Fast-track
      programs reduce postoperative morbidity and hospital stay after elective
      colorectal surgery. According to few studies, this approach seems to be safe and
      feasible in senior patients. In our institution, mortality/morbidity rates were
      0% and 37% after elective colorectal surgery in senior patients with standard
      care, with a median hospital stay of 13 days. Elective colorectal surgery should
      be offered to senior patients. However the relative high morbidity rate with
      standard care prompts us to initiate a specifically designed fast-track protocol
      in senior patients.

PMID- 19772201
TI  - [General practice: complexities and uncertainties].

PMID- 19772202
TI  - [Emile Papiernik, French pioneer of modern obstetrics (1936-2009)].

PMID- 19772203
TI  - [The shadow of the influenza A (H1N1) in Mecca].

PMID- 19772204
TI  - [Your genome sequence for the price of a car].

PMID- 19772205
TI  - Senior reach outcomes in comparison with the Spokane Gatekeeper program.
AB  - Senior Reach program outcomes for older adults referred for care management and
      mental health services through a Gatekeeper model were examined in this study and
      compared with the Spokane Gatekeeper model. The two programs were compared for
      seniors served on service variables and outcome ratings for isolation,
      depression, and functioning. Approximately 41% of seniors served by both programs
      were referred by nontraditional sources: community gatekeepers. Findings indicate
      that individuals served by the Senior Reach program demonstrated significant
      improvement in reduction of isolators (such as social isolation), improved
      functioning, increased optimism about the future, increased positive activities
      with others, decreased emotional disturbance, and improvements on the Geriatric
      Depression Scale. Additional program comparisons and findings are discussed.
      Findings for the Senior Reach program demonstrate that the gatekeeper approach to
      training community partners is effective in finding at-risk seniors and meeting
      their needs, resulting in positive impacts on their lives.

PMID- 19772206
TI  - Development of an individualized service plan tool and rules for case management
      in Quebec.
AB  - From past experience with integrated service delivery, there appears to be a need
      for a clinical tool to help case managers plan, monitor, and coordinate services.
      In this context the Quebec Ministry of Health and Social Services created a task
      force to suggest improvements to the Individualized Service Plan tool included in
      the Multiclientele Assessment Tool. This article reports the findings of this
      multidisciplinary task force working with various clienteles (older, with
      physical or mental disabilities, mental diseases). Based on a literature review
      and recent results from the Program of Research on the Integration of Services
      for the Maintenance of Autonomy, the task force proposed a dynamic, concise, user
      friendly tool and a clear definition of how it should be used. The Individualized
      Service Plan must list the patient's needs, with an orientation regarding the
      action plan for each, and a list of services allocated in response to these needs
      that work in the defined direction. The tool must also contain a section for
      analyzing variations between the services needed and allocated. This tool was
      presented to case managers for validation and received an enthusiastic response.
      It should be implemented in the coming years in the provincial Multiclientele
      Assessment Tool.

PMID- 19772207
TI  - Efficient and accurate measurement of physical restraint use in acute care.
AB  - OBJECTIVES: Describe and evaluate a method for assessing whether physical
      restraint prevalence differs by timing and frequency of data collection and to
      determine the minimum period of observation necessary to provide accurate
      prevalence estimates on both Intensive Care Unit (ICU) and medical-surgical
      units. DESIGN: Two-period, cross-sectional design with repeated observations in
      year 1 for 18 consecutive days and in year 2 for 21 consecutive days with method
      modifications. SETTING: 400-bed urban teaching hospital. PARTICIPANTS: All beds
      on general medical, surgical, and intensive care units. MEASUREMENT: Direct
      observation of patients, nurse interview, and medical record review conducted by
      trained observers. RESULTS: There were no significant differences in mean
      restraint use prevalence rates comparing: (a) morning and evening periods; (b)
      weekdays and weekend days; and (c) observation periods of 7, 14, or 21
      consecutive days or for 7 days using every 3rd day on either medical-surgical
      units or ICUs. Analyses using data from an increasing number of days of
      observation indicates that the mean prevalence rate stabilizes after 16 days.
      There were larger mean differences for comparisons on ICU-ventilator units and
      lack of significant differences may be due to low statistical power. CONCLUSION:
      Direct observation by trained observers, supplemented by nurse report and medical
      record documentation over brief monitoring periods, results in accurate,
      nonintrusive, cost-efficient estimates of physical restraint prevalence. As few
      as seven consecutive or nonconsecutive days in measuring restraint prevalence is
      sufficient to obtain accurate estimates, although the number of days may vary
      depending on patient mix and unit type.

PMID- 19772208
TI  - An emerging model of primary care for older adults: the house call-home care
      practice.
AB  - House calls to older adults have become more common, in part related to the
      emergence of medical practices that either emphasize or exclusively provide house
      calls. In this article we seek to describe organizational, clinician, and patient
      characteristics of house call-home medical care practices in the United States.
      We conducted telephone interviews with clinicians representing 36 randomly
      selected practices from across the United States. This study found that house
      call-home care practices typically are recently formed small groups of physicians
      and nurse practitioners that provide in-home primary care, especially chronic
      disease care, to Medicare beneficiaries. Clinicians are motivated by the
      opportunity to improve care and to maintain autonomy. This emerging model may
      represent a mutually beneficial trend for older adults and physicians.

PMID- 19772209
TI  - New York City's Foster Grandparent Program: a model of older volunteer
      management.

PMID- 19772210
TI  - A different approach to providing care to Utah's nursing home patients in a high
      cost, dynamic environment.

PMID- 19772211
TI  - Long-term care in the home for people with multiple sclerosis.

PMID- 19772212
TI  - [Prevention of deep venous thrombosis after knee arthroscopy. Recent advances].
AB  - In absence of prophylaxis, the incidence of deep vein thrombosis after knee
      arthroscopy is reported to be as high as 18%. Recommendations for
      thromboprophylaxis after knee arthroscopy have actually been updated. The results
      of the largest randomized clinical trial (KANT study) in this setting are
      reported together with a review of the literature.

PMID- 19772213
TI  - [Prevention of post-surgical recurrence of Crohn's disease. A perspective].
AB  - Crohn's disease often leads to stricture formation, occlusion and surgery.
      Unfortunately the disease tends to recur often. Traditional medications seem very
      little effective for recurrence prevention. By contrast, biologics appear
      extremely promising and potentially capable of changing radically the management
      of this disease.

PMID- 19772214
TI  - [Between science and suffering: difficult conversations in healthcare].
AB  - INTRODUCTION: This article describes the adaptation and implementation of the
      Program to Enhance Relational and Communication Skills (PERCS) in Italy. PERCS
      was originally developed at Children's Hospital Boston and aims to enhance
      clinicians' preparedness to engage in difficult conversations with
      patients/families. DESCRIPTION: After a period of collaboration by the first
      author with the Children's Hospital Boston, PERCS was launched at San Paolo
      Hospital, Milan, in 2008. To date, over 80 participants have voluntarily attended
      the program. The program features monthly 4-hour workshops geared around the
      enactment of a case scenario by trained actors and participants. Each workshop
      enrolls 10-13 interdisciplinary participants. After each enactment, participants
      receive feedback by actors, other participants and facilitators on the
      challenging junctures of the conversation. Pedagogical principles include:
      creating safety for learning; emphasizing moral and relational dimensions of
      care; suspending hierarchy among participants; valuing self-reflection; honoring
      multiple perspectives; and offering continuity of the educational offering.
      CONCLUSIONS: Implementing PERCS in Italy has demonstrated that it is possible to
      culturally adapt learning opportunities that embrace the relational and ethical
      experience of learners. The positive response of participants affirms that
      relational learning is meaningful and needed.

PMID- 19772215
TI  - [An atypical case of cardiac amyloidosis].
AB  - The described report deals with the case of a patient with diagnosis of ischemic
      hypertensive cardiomyiopathy based on the history of angina and inducible
      myocardial ischemia with normal coronary arteries. However, after cardiac
      magnetic resonance, the typical amyloidotic pattern is found and the final
      diagnosis of multiple myeloma is made at osteomedullary biopsy.

PMID- 19772216
TI  - [Anti-PR3 positive inflammatory bowel disease. Description of a case].
AB  - We descrive the case of a patient with inflammatory bowel disease complicated by
      erythema nodosum and anti PR3 positivity. The patient was exposed to two
      different bacteria: salmonellosis was reported in patient history, while
      Staphylococcus aureus infection was diagnosed during the present hospital stay.
      Antibiotics and steroids are effective.

PMID- 19772217
TI  - [The lack of good manners in medicine: sign of the times or educational gap?].

PMID- 19772218
TI  - [Observation Unit].
AB  - Observation Unit is an extention of Emergency Department for evaluation and
      stabilization of patients beyond the traditional 2- to 3-hour limit. A benefit of
      this continued patient management is better definition of the patient's problem,
      with resulting reduction in costs and inappropriate dispositions. The ultimate
      goal is to improve the quality of medical care for patients through extended
      evaluation and treatment while reducing inappropriate admissions and health care
      costs.

PMID- 19772219
TI  - [Oral and cervical lesions associated with human papillomavirus].
AB  - The aim of this review is to carry out a quick excursus on the epidemiological
      and clinical aspect of oral and cervical lesions induced by human papillomavirus
      (HPV) infection and on the way this virus is transmitted. HPV infection is
      transmitted above all through vaginal or anal sexual relations with partners
      carrying the virus. Also other types of sexual relations, such as oral sex, can
      be a vehicle of transmission, though much more rarely. In literature there is not
      enough data proving that oral-genital contact can really be a vehicle of
      transmission for human papillomavirus. It can be concluded, therefore, that
      evidences in further studies with a large sample group of patients who practise
      oral sex on HPV-positive subjects are necessaries.

PMID- 19772220
TI  - [The gastrointestinal risk of antiplatelet agents and nonsteroidal anti
      inflammatory agents. A report of the American College of Cardiology Foundation
      (ACCF), the American College of Gastroenterology (ACG) and the American Heart
      Association (AHA)].

PMID- 19772221
TI  - Corneal collagen cross-linking for ectasia after excimer laser refractive
      surgery: 1-year results.
AB  - PURPOSE: To evaluate the 1-year results of corneal collagen cross-linking (CXL)
      in eyes with postoperative excimer laser refractive surgery corneal ectasia.
      METHODS: Thirteen eyes of 9 consecutive patients who had undergone excimer laser
      refractive surgery (photorefractive keratectomy [n = 3], LASIK [n = 10]) with
      resultant unstable corneal ectasia underwent CXL with photosensitizing riboflavin
      0.1% solution and subsequent exposure to ultraviolet radiation. Study eyes
      underwent complete ophthalmologic examination, endothelial specular microscopy,
      corneal topography, and aberrometry as well as central pachymetry and Scheimpflug
      based topo/tomography preoperatively and at 3-, 6-, and 12-month intervals.
      RESULTS: Best spectacle-corrected visual acuity (BSCVA) improvement was
      statistically significant (P < .05) beyond 6 months after surgery (improvement of
      0.1 logMAR at 1 year). Mean spherical equivalent refraction and mean refractive
      sphere reduction (improvement of 1.40 and 1.44 diopters [D], respectively) were
      statistically significant (P < .05) at 6 months postoperatively. At 1 year after
      CXL, mean endothelial cell count and keratometry (average SimK decrease of 2.02
      D) as well as Klyce and Ambrosio indices did not deteriorate. Coma and spherical
      aberration did not change significantly. Mean pupil center pachymetry and corneal
      thickness at 0 and 2 mm from the thinnest corneal point decreased significantly.
      CONCLUSIONS: One year after surgery, CXL appears to stabilize eyes with ectasia
      consequent to excimer laser refractive surgery and improve BSCVA.

PMID- 19772222
TI  - Transplantation of endothelium and descemet membrane for aphakic corneal edema in
      1980.
AB  - PURPOSE: To describe a corneal endothelial layer and Descemet membrane
      transplantation into the anterior chamber for the treatment of bullous
      keratopathy in 1980. METHODS: A retrospective report of an intervention case
      study is presented. A patient with aphakic bullous keratopathy in one eye was
      interested in undergoing a previously untested corneal transplantation procedure.
      Snellen visual acuity testing and slit-lamp examination were performed. The main
      outcome measures were visual acuity and degree of corneal clarity. RESULTS:
      Visual acuity and corneal clarity improved in the months following the
      endothelial/Descemet membrane transplant but gradually returned to preoperative
      levels 1 year later. A subsequent successful penetrating keratoplasty resulted in
      excellent visual acuity (-20/25). CONCLUSIONS: An attempt to perform endothelial
      and Descemet membrane transplantation for aphakic corneal edema in 1980 resulted
      in early improvement in corneal clarity and visual acuity but required full
      penetrating keratoplasty at 2 years postoperatively. [J Refract Surg.
      2010;26(7):525-528.] doi:10.3928/1081597X-20090910-01

PMID- 19772223
TI  - Medication adherence and older renal transplant patients' perceptions of
      electronic medication monitoring.
AB  - This study evaluated older renal transplant recipients' perceptions of electronic
      medication monitoring and the influence of these perceptions on medication
      adherence. A sample of 73 older adult renal transplant recipients who used the
      Medication Event Monitoring System (MEMS((r))) TrackCaps for 12 months provided
      their perceptions of device use. Participants perceived that the MEMS had a
      neutral effect on their medication-taking routine (65%), believed the MEMS was
      practical (56%), and could not describe any instances in which using the MEMS was
      difficult (56%). No significant difference in medication adherence was found
      between those who perceived the MEMS's influence negatively/neutrally and those
      who perceived the MEMS positively (p = 0.22). Medication adherence data from
      older adult renal transplant recipients can be used regardless of their
      perceptions of the MEMS's influence on their medication taking without biasing
      medication adherence data.

PMID- 19772224
TI  - The importance of living wills and advance directives.
AB  - Living wills and advance directives are important components of patients' medical
      records, which all too often do not indicate the appropriate palliative care
      measures the patient desires. A review of the current literature indicates that
      approximately 85% to 95% of the population does not have adequate advance
      directives or palliative care measures written in their medical record.
      Furthermore, these orders may not follow the patient when he or she is
      transferred to other facilities for intermittent care. Unwanted tracheal
      intubations can be both costly to the facility and distressing to the patient and
      family members. By instituting a change in policy, organizations can ensure that
      patients' wishes for end-of-life care are met appropriately. In addition, nurses
      should advocate for a centralized database at the political level.

PMID- 19772225
TI  - Sarah Hall Gueldner, DSN, RN, FAAN.

PMID- 19772226
TI  - Taiwanese Nursing Students' Attitudes Toward Older People.
AB  - The aim of this research was to establish Taiwanese undergraduate nursing
      students' attitudes toward older people. This study involved a cross-sectional
      survey of 362 nursing students in a university in southern Taiwan. Overall, the
      results showed that nursing students had positive attitudes toward older people.
      Moreover, the findings suggested that nursing students' intention to work with
      older people and gender were important factors influencing their attitudes toward
      older people. The findings of this study indicate that efforts are required to
      maintain these positive attitudes. In addition, provision of nursing courses
      related to older people that place greater emphasis on attitudes about aging and
      that take into account students' working experience and career intention will
      lead to higher quality of care for older people.

PMID- 19772227
TI  - Identifying and treating wound infection.
AB  - The presence of infection is a major causative factor for delayed or nonhealing
      wounds. Indiscriminate and routine wound cultures are not recommended, but after
      the clinical diagnosis of infection is made, culture is recommended to identify
      the causative organisms and guide antibiotic therapy. The purpose of this article
      is to discuss how to identify and confirm wound infection and the use of topical
      and systemic antibiotic agents to treat wound infection.

PMID- 19772228
TI  - Younger residents in nursing homes.
AB  - Younger residents in nursing facilities represent a growing but little recognized
      population. This study examined a group of younger residents, describing issues
      identified by residents and facility staff and identifying strategies that might
      improve their quality of life. In this study, the majority of younger residents
      were men with significant physical and mental health deficits, who spent most of
      their time alone or watching television. Residents wanted a greater variety of
      relevant recreational activities and more meaningful relationships with family,
      staff, and other residents. Staff believed nursing facilities were not designed
      for younger residents, resulting in unmet psychosocial and recreational needs.

PMID- 19772229
TI  - Instruments for measuring fall risk in older adults living in long-term care
      facilities: an integrative review.
AB  - Lack of consistency in the literature regarding the use of fall risk assessment
      in long-term care settings and the uniqueness of the environment demand a
      critical analysis of fall risk instruments specific to older adults living in
      long-term care facilities. This integrative review of the existing literature on
      instruments used to measure fall risk in residents living in long-term care
      facilities revealed a total of 16 fall risk assessment tools from 13 studies. Of
      the 13 studies, only 8 reported sensitivity, specificity, and interrater
      reliability values of the tools. Only the Morse Fall Scale and Mobility Fall
      Chart demonstrated high predictive values in their initial developmental studies.
      This review can help clinicians make informed choices about tools to predict
      falls in their settings and establish appropriate preventive interventions.

PMID- 19772230
TI  - The medical home.

PMID- 19772231
TI  - This issue: the family-centered medical home in pediatrics.

PMID- 19772232
TI  - A 12-hour-old girl with multiple congenital anomalies.

PMID- 19772233
TI  - A 3-day-old boy with acute flaccid paralysis.

PMID- 19772234
TI  - Medical home 2009: what it is, where we were, and where we are today.

PMID- 19772235
TI  - Achieving effective care coordination in the medical home.

PMID- 19772236
TI  - Communication, comanagement, and collaborative care for children and youth with
      special healthcare needs.

PMID- 19772237
TI  - Family-centered, culturally, and linguistically competent care: essential
      components of the medical home.

PMID- 19772238
TI  - On the threshold to the adult medical home: care coordination in transition.

PMID- 19772239
TI  - The medical home: an essential competency for pediatric residents.

PMID- 19772241
TI  - Supporting soldiers returning to our communities after combat missions.

PMID- 19772240
TI  - Looming financial issues for medical homes in healthcare reform.

PMID- 19772244
TI  - Weight gain with atypical antipsychotic drugs in bipolar disorder.
AB  - Diana is a 21-year-old student who lives with her parents. She had been enrolled
      in college but has taken a temporary leave of absence due to the instability of
      her bipolar disorder. Since being diagnosed at age 18, Diana's treatment team has
      been unable to find a medication regimen that would maintain her stability. She
      has had several breakthrough manic episodes that resulted in significant risky
      and inappropriate behaviors on campus. The cognitive, motivational, and energy
      limitations of depression left her unable to keep up with school requirements.
      Dr. Spiker, her regular psychiatrist, prescribed olanzapine Zyprexa 5 mg. Both
      Diana and Dr. Spiker are concerned about potential weight gain but consider this
      intervention necessary, as other medication trials have been unsuccessful.

PMID- 19772246
TI  - Medication holidays.
AB  - Medication holiday refers to the deliberate interruption of pharmacotherapy for a
      defined period and for a specific clinical purpose. This should be distinguished
      from medication nonadherence. Medication holidays can be used for the assessment
      of efficacy and tolerability of a drug therapy. They also can be used for a
      therapeutic benefit, such as alleviating adverse effects. To partially reverse
      the physiological adaptive effects that result from chronic pharmacological
      stimulation, medication holidays have been hypothesized to "resensitize" neurons
      to the acute pharmacological effects of a drug. Potential problems associated
      with medication holidays include the risk of destabilizing patients, difficulty
      in distinguishing rebound and discontinuation effects, and increasing the risk of
      poor medication adherence.

PMID- 19772247
TI  - Caregiver burden or caregiver gain?
AB  - Many caregivers of older family members do not realize the need for respite until
      their own health begins to deteriorate. The mental, emotional, and physical
      stress of caring for a family member can seem overwhelming. Creative options for
      respite care are emerging, but there are barriers to effective use of these
      programs. This article discusses these barriers and proposes suggestions for
      overcoming them.

PMID- 19772248
TI  - Mental health needs in a post-disaster environment.
AB  - Maintenance of a daily routine, which includes scheduled medications, access to a
      health care provider, and a stable environment, forms an anchor point in the
      lives of people diagnosed with mental illness. When a disaster, either man made
      or natural, interferes with these, patients often experience an acute
      exacerbation of their illness. Efforts to mitigate the ensuing disruption require
      a contingency plan in the event of a disaster; a plan ensuring access to
      medications, health information, and caregiver stability, allows those with
      mental illness to continue to function at an acceptable level. Recent world
      events, such as the Asian Tsunami in 2004 and Hurricane Katrina in 2005, indicate
      that minimal research exists regarding the magnitude of the effects of disasters
      on those with mental illness. A review of the literature indicates that the
      impact on survivors' mental well-being is directly related to the level of
      exposure to a disaster. Mental health professionals must include crisis
      management, planning, and communication in pre- and post-disaster interventions
      with people who have mental illness.

PMID- 19772249
TI  - Behavioral management of auditory hallucinations.
AB  - A 10-session behavioral course for self-management of auditory hallucinations in
      patients with schizophrenia has demonstrated positive outcomes. This article
      evaluates both the course's implementation and benefits to patients attending the
      course. Teleconferencing, electronic media, and 26 monthly conference calls were
      used to educate six advanced practice nurses (APNs) at six sites about the course
      implementation. Thirty-two patients within the U.S. Department of Veterans
      Affairs participated in the course. All of the APNs reported course helpfulness,
      improved communication with patients about voices, and improved harm assessment.
      Of the patients, 96% found the course helpful: 67% no longer heard voices to harm
      self or others, and 60% had improved auditory hallucination intensity scores. The
      project demonstrated successful implementation and practice integration with
      APNs' activities corresponding to Rogers' stages of innovation adoption.
      Facilitators and barriers to implementation are also described.

PMID- 19772250
TI  - Psychiatric nurses' decision to restrain.
AB  - The use of restraints in all health care settings has come under increased
      scrutiny in recent years. Although the organizational context has been suggested
      as a possible influence on restraint use, few researchers have examined whether
      organizational factors affect use of restraints and nurses' decisions to restrain
      patients hospitalized in psychiatric facilities. The purpose of this study was to
      examine the association of nurses' work empowerment (an indicator of
      organizational culture) with nurses' decision to restrain. This study also
      examined the association between individual characteristics of the patient and of
      the nurses with nurses' decision to restrain. Lastly, this study examined the
      decision patterns used by psychiatric nurses in response to patient situations in
      which restraint might be considered.

PMID- 19772252
TI  - Introduction to the proceedings of the fourth international congress of corneal
      cross linking.

PMID- 19772253
TI  - Influence of high-dose cortisol on the biomechanics of incubated porcine corneal
      strips.
AB  - PURPOSE: To investigate the change in biomechanical properties of the cornea
      induced by high-dose hydrocortisone. METHODS: The influence of hydrocortisone was
      investigated in 12 fresh porcine corneas incubated in culture medium of 2.5 muM
      of hydrocortisone for 7 days. Twelve additional porcine corneas incubated in
      culture medium without hydrocortisone for the same time served as the control
      group. Strips of cornea were cut and the stress-strain relationship was measured
      in a biomaterial tester. Young's modulus was calculated. RESULTS: After
      incubation, the thickness of the cornea was 1120+/-130 mum in the control group
      and 1320+/-90 mum in the hydrocortisone group. The hydrocortisone-treated corneas
      were 18% thicker compared to the control corneas. However, the difference in the
      biomechanical stress value at 10% strain was significantly larger. In the control
      group, the stress value measured 122+/-40 kPa, and in the hydrocortisone group,
      it measured 77+/-19 kPa (P=.003), representing a reduction of the corneal
      stiffness by 37% due to hydrocortisone treatment. Young's modulus was reduced by
      42.8% from 2.90+/-1.10 MPa in the control group to 1.66+/-0.49 in the
      hydrocortisone group. CONCLUSIONS: Hydrocortisone is a modulating factor of the
      biomechanical properties of the cornea. The significance of the cortisol status
      of the patient and its influence on the biomechanical stability of the cornea
      should be considered in the development of keratectasia in keratoconus or after
      refractive surgery.

PMID- 19772254
TI  - In vitro antimicrobial efficacy of riboflavin and ultraviolet light on
      Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, and
      Pseudomonas aeruginosa.
AB  - PURPOSE: Ultraviolet (UV) light and riboflavin has been developed as a collagen
      cross-linking treatment for corneal ectasia. This treatment has also been used to
      treat infectious corneal ulcers with apparent favorable results. In this
      experiment, the antibacterial action of riboflavin alone, UV light alone, and the
      combination of riboflavin and UV light was tested on Staphylococcus aureus,
      methicillin-resistant S aureus (MRSA), and Pseudomonas aeruginosa. METHODS:
      Thirty agar plates with S aureus overlays were used. Ten plates were exposed to
      riboflavin (0.1% solution in dextran) alone, 10 plates were exposed to UV light
      (365 nm) alone, and 10 plates were exposed to a combination of riboflavin and UV
      light. Fifteen agar plates with MRSA and 15 plates with P aeruginosa were tested.
      Five plates of each group were exposed to riboflavin, 5 plates of each group were
      exposed to UV light alone, and 5 plates of each group were exposed to a
      combination of riboflavin and UV light. All plates were incubated for 24 hours
      and then analyzed. RESULTS: All plates exposed to riboflavin alone showed no
      bacterial death. All S aureus and MRSA plates exposed to UV light alone showed no
      bacterial growth. Three of five P aeruginosa plates exposed to UV light alone
      showed no bacterial death; two of five P aeruginosa plates exposed to UV light
      alone showed minimal inhibition. All plates exposed to the combination of
      riboflavin and UV light showed bacterial death. CONCLUSIONS: Riboflavin in
      combination with UV light is an effective modality to eradicate the bacteria S
      aureus, MRSA, and P aeruginosa.

PMID- 19772255
TI  - Riboflavin-UVA treatment in the management of edema and nonhealing ulcers of the
      cornea.
AB  - PURPOSE: Riboflavin-ultraviolet A (UVA) treatment induces cross-linking and
      stiffens the corneal stroma. A parallel reduction in stromal swelling and
      increased resistance to microbial and enzymatic degradation has been suggested.
      The purpose of this study was to evaluate the potential of riboflavin-UVA
      treatment in the management of corneal disorders, in particular edema due to
      endothelial decompensation and non-healing ulcers. METHODS: Two clinical series
      are reported, 11 eyes with endothelial decompensation and 14 eyes with non
      healing ulcers. Treatment comprised a) abrasion of epithelium (if present), b)
      instillation of 0.1% riboflavin in saline, and c) irradiation at 365 nm UVA light
      over approximately 30 minutes (3 mW/cm(2)). Four eyes in the first group were
      treated twice. Postoperatively, all eyes were followed for at least 3 months.
      RESULTS: Reduction in corneal thickness was observed in 10 of 11 eyes with
      stromal edema and the majority also experienced improvement in vision. The effect
      occurred over weeks and lasted for months. Fourteen patients with non-healing
      ulceration were similarly treated; 6 healed, 8 showed no clear effect.
      CONCLUSIONS: In addition to the stiffening of keratoconic and ectatic cornea,
      riboflavin-UVA treatment is effective in reducing corneal edema and has the
      potential to heal corneal ulcers.

PMID- 19772256
TI  - Simultaneous topography-guided PRK followed by corneal collagen cross-linking for
      keratoconus.
AB  - PURPOSE: To present the results after simultaneous photorefractive keratectomy
      (PRK) followed by corneal collagen cross-linking (CXL) for progressive
      keratoconus. METHODS: Twelve patients (14 eyes) with progressive keratoconus were
      prospectively treated with customized topography-guided PRK with the Pulzar Z1
      (wavelength 213 nm, CustomVis) immediately followed by corneal collagen CXL with
      the use of riboflavin and ultraviolet A irradiation. RESULTS: Mean follow-up was
      10.69+/-5.95 months (range: 3 to 16 months). Mean preoperative spherical
      equivalent refraction (SE) was -3.03+/-3.23 diopters (D) and defocus was 4.67+/
      3.29 D; at last follow-up SE and defocus were statistically significantly reduced
      to -1.29+/-2.05 D and 3.04+/-2.53 D, respectively (P<.01). Preoperative mean
      (logMAR) uncorrected visual acuity was 0.99+/-0.81 and best spectacle-corrected
      visual acuity was 0.21+/-0.19, which improved postoperatively to 0.16+/-0.15 and
      0.11+/-0.15, respectively. The mean steepest keratometry was reduced from 48.20+/
      3.40 D preoperatively to 45.13+/-1.80 D at last follow-up. CONCLUSIONS:
      Simultaneous PRK followed by CXL seems to be a promising treatment capable of
      offering functional vision in patients with keratoconus.

PMID- 19772257
TI  - Comparison of sequential vs same-day simultaneous collagen cross-linking and
      topography-guided PRK for treatment of keratoconus.
AB  - PURPOSE: The safety and efficacy of corneal collagen cross-linking (CXL) and
      topography-guided photorefractive keratectomy (PRK) using a different sequence
      and timing were evaluated in consecutive keratoconus cases. METHODS: This study
      included a total of 325 eyes with keratoconus. Eyes were divided into two groups.
      The first group (n=127 eyes) underwent CXL with subsequent topography-guided PRK
      performed 6 months later (sequential group) and the second group (n=198 eyes)
      underwent CXL and PRK in a combined procedure on the same day (simultaneous
      group). Statistical differences were examined for pre- to postoperative changes
      in uncorrected (UCVA, logMAR) and best-spectacle-corrected visual acuity (BSCVA,
      logMAR), manifest refraction spherical equivalent (MRSE), keratometry (K),
      topography, central corneal thickness, endothelial cell count, corneal haze, and
      ectatic progression. Mean follow-up was 36+/-18 months (range: 24 to 68 months).
      RESULTS: At last follow-up in the sequential group, the mean UCVA improved from
      0.9+/-0.3 logMAR to 0.49+/-0.25 logMAR, and mean BSCVA from 0.41+/-0.25 logMAR to
      0.16+/-0.22 logMAR. Mean reduction in spherical equivalent refraction was 2.50+/
      1.20 diopters (D), mean haze score was 1.2+/-0.5, and mean reduction in K was
      2.75+/-1.30 D. In the simultaneous group, mean UCVA improved from 0.96+/-0.2
      logMAR to 0.3+/-0.2 logMAR, and mean BSCVA from 0.39+/-0.3 logMAR to 0.11+/-0.16
      logMAR. Mean reduction in spherical equivalent refraction was 3.20+/-1.40 D, mean
      haze score was 0.5+/-0.3, and mean reduction in K was 3.50+/-1.3 D. Endothelial
      cell count preoperatively and at last follow-up was unchanged (P<.05) in both
      groups. Statistically, the simultaneous group did better (P<.05) in all fields
      evaluated, with improvement in UCVA and BSCVA, a greater mean reduction in
      spherical equivalent refraction and keratometry, and less corneal haze.
      CONCLUSIONS: Same-day simultaneous topography-guided PRK and CXL appears to be
      superior to sequential CXL with later PRK in the visual rehabilitation of
      progressing keratoconus.

PMID- 19772258
TI  - Keratitis and corneal scarring after UVA/riboflavin cross-linking for
      keratoconus.
AB  - PURPOSE: To report four cases of severe keratitis after standard corneal collagen
      cross-linking (CXL) treatment for keratoconus. METHODS: Four patients with
      progressive keratoconus from two different centers were treated by ultraviolet A
      (UVA) CXL, using riboflavin as a photosensitizer. The epithelium was removed over
      the central 8 to 9 mm of the cornea. Riboflavin 0.1% in dextran 20% was instilled
      every 2 minutes for 30 minutes before UVA exposure. The UV-X light source (IROC),
      calibrated at 3 mW/cm(2), was applied for 30 minutes while instillation was
      continued every 2 minutes. At the end of the treatment, a bandage contact lens
      was applied and topical treatment consisting of a combination of antibiotics
      and/or anti-inflammatory drops was initiated. RESULTS: Patients experienced
      delayed (after more than 24 hours) symptoms and signs of inflammation. The eyes
      showed pronounced ciliary redness with cells in the anterior chamber and central
      keratic precipitates; multiple white infiltrates had developed at the edge and
      within the area of CXL. High-dose topical or subconjunctival corticosteroids led
      to rapid initial improvement of symptoms and signs. Herpes virus could not be
      detected on the ocular surface or on the anterior chamber tap of one patient.
      CONCLUSIONS: We report four cases of keratitis and corneal scarring from a total
      of 117 eyes treated with CXL. The location of the scarring determined the amount
      of loss of visual acuity: in two eyes, there was a persistent decrease in best
      spectacle-corrected visual acuity.

PMID- 19772259
TI  - Permanent corneal haze after riboflavin-UVA-induced cross-linking in keratoconus.
AB  - PURPOSE: Retrospective evaluation of haze development after riboflavin
      ultraviolet (UV) A-induced corneal collagen cross-linking (CXL). METHODS: One
      hundred sixty-three eyes of 127 patients with stage 1-3 keratoconus according to
      Krumeich's classification were included in this retrospective analysis. Follow-up
      was 1 year. Preoperatively and at all follow-up examinations uncorrected visual
      acuity, best spectacle-corrected visual acuity (BSCVA), slit-lamp microscopic
      findings, corneal topography, and corneal thickness were recorded. RESULTS: At 1
      year after CXL, 149 (91.4%) eyes of 114 patients had a clear cornea without
      stromal haze (control group), whereas 14 eyes (8.6%) of 13 patients developed
      clinically significant stromal haze (haze group). Preoperatively, the mean
      keratometry (K) value of the apex was 62.1+/-13.8 diopters (D) in the control
      group and 71.1+/-13.2 D in the haze group (P=.02). The mean corneal thickness
      before the procedure was 478.1+/-52.4 mum in the control group and 420.0+/-33.9
      mum in the haze group (P=.001). Uncorrected visual acuity and BSCVA, which were
      similar between groups preoperatively (P=.59 and P=.75, respectively), were
      improved in the control group (P=.023 and P=.001, respectively), but reduced in
      the haze group (P=.012 and P=.004, respectively) postoperatively. CONCLUSIONS:
      The parameters defining the stage of keratoconus, such as K-value and corneal
      thickness, could be considered predicting factors for possible development of
      corneal haze after riboflavin-UVA-induced CXL. Advanced keratoconus should be
      considered at higher risk of haze development after CXL due to low corneal
      thickness and high corneal curvature.

PMID- 19772260
TI  - Artisan phakic intraocular lens in patients with keratoconus.
AB  - PURPOSE: To assess the safety, efficacy, predictability, and refractive outcome
      of implanting Ophtec Artisan phakic intraocular lenses (pIOLs) in eyes with
      keratoconus. METHODS: In this retrospective study, 18 eyes of 11 patients
      diagnosed with keratoconus who underwent toric or myopic pIOL implantation were
      followed for 1 year postoperatively. Mean patient age was 41+/-10.97 years
      (range: 23 to 64 years). Preoperative manifest refractive sphere was -4.64+/-2.74
      diopters (D) (range: -9.75 to 0.00 D) and cylinder was -3.07+/-2.04 D (range: 
      7.75 to -0.50 D). Inclusion criteria were preoperative best spectacle-corrected
      visual acuity (BSCVA) of 0.30 or better and stable refraction (</=0.50-D change
      in manifest refraction spherical equivalent [MRSE] yearly). Refractive outcomes
      and endothelial cell counts were analyzed primarily for 6-month follow-up and
      when available for 1-year follow-up. RESULTS: The mean postoperative MRSE was 
      0.46+/-0.60 D (range: -1.88 to 0.13 D). Twenty-two percent (4/18) of eyes had an
      uncorrected visual acuity (UCVA) of 1.0 or better and 94% (17/18) of eyes had a
      UCVA of 0.63 or better. Sixty-one percent (11/18) of eyes had an MRSE within +/
      0.50 D of the intended correction and 72% (13/18) of eyes gained one or more
      lines of BSCVA and no eyes lost lines of BSCVA. Mean endothelial cell counts
      decreased by 23 cells/mm(2) at 6 months postoperatively. CONCLUSIONS: The
      implantation of Artisan iris-fixated pIOLs in patients with stable keratoconus
      for correction of astigmatism and myopia is safe, predictable, and effective with
      minimal complications. Due to the progressive nature of keratoconus, proper
      patient counseling is necessary.

PMID- 19772261
TI  - Comparison of the Visian ICL and Verisyse phakic intraocular lenses for myopia
      from 6.00 to 20.00 diopters.
AB  - PURPOSE: To compare visual and refractive outcomes between the Visian Implantable
      Collamer Lens (ICL) and Verisyse phakic intraocular lens. METHODS: Comparative
      interventional case series for myopia between 6.00 and 20.00 diopters (D). Thirty
      consecutive eyes of 16 patients had a Visian ICL implanted and 31 consecutive
      eyes of 19 patients had the Verisyse lens implanted. Outcomes measured at 3
      months postoperatively included uncorrected visual acuity (UCVA), best spectacle
      corrected visual acuity (BSCVA), and refractive predictability as well as adverse
      events. Preoperatively, the groups were no different in regard to age (P=.72) and
      spherical equivalent refraction (P=.38). RESULTS: Postoperative UCVA of 20/20 or
      better and 20/25 or better in the Visian ICL group was 67% and 96%, respectively,
      compared to 63% and 79%, respectively, in the Verisyse lens group (P=.10).
      Binocular UCVA of 20/20 or better and 20/25 or better in the Visian ICL group was
      92% and 100%, respectively, and in the Verisyse group, 70% and 80%, respectively
      (P=.007). One and two lines gain of postoperative BSCVA in the Visian ICL group
      was 40% and 10%, respectively, which was statistically significantly better than
      the Verisyse group of 16% and 6%, respectively (P=.025). Postoperative deviation
      from target refraction was 0.038+/-0.39 D in the Visian ICL group and -0.38+/
      0.89 D in the Verisyse lens group (P=.018). CONCLUSIONS: Monocular UCVA was
      similar for both groups, whereas binocular UCVA was better in the Visian ICL
      group. The Visian ICL group had more accurate refractive outcomes than the
      Verisyse lens group.

PMID- 19772262
TI  - Effect of epithelial retention and removal on riboflavin absorption in porcine
      corneas.
AB  - PURPOSE: To compare stromal riboflavin absorption after 20% alcohol application
      and partial or complete epithelial removal by analyzing light transmission
      properties of porcine corneas after riboflavin/ultraviolet A (UVA) corneal
      collagen cross-linking. METHODS: Riboflavin 0.13% eye drops were applied to 18
      porcine eyes (6 in which 20% alcohol solution had been applied for 40 seconds, 6
      eyes with a grid pattern of full-thickness epithelial trauma, and 6 with the
      central epithelium fully removed) at 5-minute intervals for 35 minutes. In all
      eyes, the corneal surface was exposed to UVA light for 30 minutes during
      riboflavin administration. The light transmission spectra of the corneas were
      analyzed with a spectrophotometer and compared to those of 9 untreated controls
      (4 corneas with epithelium and 5 without) and to the spectra of riboflavin 0.13%
      solution. RESULTS: The spectra of riboflavin-treated corneas in the alcohol group
      were similar to controls. Those with grid-pattern epithelial trauma showed a dip
      in light transmission between 400 and 490 nm, but this was significantly less
      than that in eyes for which epithelial removal was complete, where the spectrum
      was similar to that of riboflavin 0.13% solution. CONCLUSIONS: Complete removal
      of the corneal epithelium appears to be necessary to allow sufficient riboflavin
      absorption into the stroma to alter the normal light transmission properties of
      the porcine cornea. Although partial grid-pattern epithelial removal allows some
      riboflavin penetration, uptake is limited and non-homogeneous, which may affect
      the efficacy of the cross-linking process.

PMID- 19772264
TI  - Traumatic corneal flap dehiscence 6 years after LASIK.
AB  - PURPOSE: To report a case of LASIK flap dehiscence caused by blunt trauma 6 years
      after uneventful refractive surgery. METHODS: A 32-year-old man presented 3 hours
      after being struck by a carton edge in his left cornea, causing dehiscence of the
      LASIK flap. RESULTS: At initial examination, uncorrected visual acuity (UCVA) was
      20/200 in the left eye. Minimal flap dehiscence was seen on the inferior corneal
      quadrant. A therapeutic bandage soft contact lens was placed and topical medical
      therapy was administered. Ten days after trauma, UCVA was 20/50 and best
      spectacle-corrected visual acuity was 20/30 in the left eye. At 7-month follow
      up, the patient's clinical status did not change. CONCLUSIONS: Blunt corneal
      trauma occurring several years after uneventful LASIK may cause corneal flap
      dehiscence. Appropriate and prompt treatment usually is successful.

PMID- 19772263
TI  - Stromal thickness in the normal cornea: three-dimensional display with artemis
      very high-frequency digital ultrasound.
AB  - PURPOSE: To characterize the stromal thickness profile in a population of normal
      eyes. METHODS: Stromal thickness profile was measured in vivo by Artemis very
      high-frequency digital ultrasound scanning (ArcScan, Morrison, Colo) across the
      central 10-mm corneal diameter on 110 normal eyes. Maps of the average, standard
      deviation, minimum, maximum, and range of stromal thickness were plotted. The
      average location of the thinnest stroma was found. The cross-sectional hemi
      meridional stromal thickness profile was calculated using annular averaging. The
      absolute stromal thickness progression relative to the thinnest point was
      calculated using annular averaging as well as for 8 hemi-meridians individually.
      RESULTS: The mean stromal thickness at the corneal vertex and at the thinnest
      point were 465.4+/-36.9 mum and 461.8+/-37.3 mum, respectively. The thinnest
      stroma was displaced on average 0.17+/-0.31 mm inferiorly and 0.33+/-0.40 mm
      temporally from the corneal vertex. The average absolute stromal thickness
      progression from the thinnest point could be described by the quadratic equation:
      stromal thickness = 6.411 x radius(2) + 2.444 x radius (R(2) = 0.999). Absolute
      stromal thickness progression was independent of stromal thickness at the
      thinnest point. The increase in hemi-meridional absolute stromal thickness
      progression was greatest superiorly and lowest temporally. CONCLUSIONS: Three
      dimensional thickness mapping of the corneal stroma and stromal thickness
      progression in a population of normal eyes represent a normative data set, which
      may help in early diagnosis of corneal abnormalities such as keratoconus and
      pellucid marginal degeneration. Absolute stromal thickness progression was found
      to be independent of stromal thickness.

PMID- 19772265
TI  - Scanning electron microscopy analysis of a sputnik-like intraocular lens 28 years
      after implantation.
AB  - PURPOSE: To report a pupil-supported, iris-clip intraocular lens (IOL) that was
      explanted more than 28 years after implantation. METHODS: A pupil-supported, iris
      clip, Sputnik-like IOL was implanted in the left eye of a 33-year-old man to
      correct aphakia after extracapsular cataract extraction due to trauma. RESULTS:
      Twenty-eight years after implantation, the patient was referred to our center
      with loss of vision. Clinical examination showed dislocation of the IOL, which
      was subsequently explanted. Scanning electron microscopic examination showed a
      transparent, polymethylmethacrylate (PMMA), pupil-supported, iris-clip IOL with
      melanosomes and cell deposits (foreign-body reaction) on its surface.
      CONCLUSIONS: This case demonstrates the inertness of PMMA material and reports
      that a foreign body reaction can be induced following IOL dislocation 28 years
      after implantation.

PMID- 19772267
TI  - Analysis of actual corneal flap thickness and confounding factors between first
      and second operated eyes.
AB  - BACKGROUND AND OBJECTIVE: To calculate the actual corneal flap thickness during
      laser in-situ keratomileusis. PATIENTS AND METHODS: Fifty-four women and 26 men
      with refractive error were enrolled in the study. Flaps were created using a MK
      2000 microkeratome (Nidek, Gamagori, Japan) with a 130-microm head. The
      comparisons between both operated eyes of a patient and the correlations between
      flap thickness and confounding factors were analyzed. RESULTS: The average flap
      thicknesses were 134.0 + or - 16.5 and 112.3 + or - 14.4 microm in the first and
      second operated eye groups, respectively, and the data showed a significant
      difference between the two groups (P < .001). There were positive correlations
      between central corneal thickness and flap thickness (first group, P = .017;
      second group, P = .041). CONCLUSION: The flap thicknesses of the first operated
      eye group were thicker than those of the second operated eye group and there was
      a positive correlation between the flap thickness and central corneal thickness.
      The coefficient of variation of the flap thickness was greater in the second
      group than in the first group.

PMID- 19772266
TI  - Reproducibility of tear meniscus measurement by Fourier-domain optical coherence
      tomography: a pilot study.
AB  - BACKGROUND AND OBJECTIVE: To study the reproducibility of tear meniscus
      measurement with high-speed high-resolution Fourier-domain optical coherence
      tomography (FD-OCT). PATIENTS AND METHODS: Twenty normal participants were
      enrolled in this prospective study. The lower tear meniscus in the right eye of
      each subject was imaged by vertical scans centered on the inferior cornea and the
      lower eyelid using an FD-OCT system (RTVue; Optovue, Inc., Fremont, CA) with a
      corneal adaptor. The system performs 26,000 axial scans per second and has a 5
      micron axial resolution. Each subject was examined at two visits 30 to 60 days
      apart. Each eye was scanned twice on each visit. The scans were taken 2 seconds
      after a blink. The lower meniscus height, depth, and cornea-meniscus angle were
      measured with a computer caliper. The cross-sectional area was calculated using a
      two-triangle approximation. RESULTS: The between-visits coefficient of variation
      was 17.5%, 18.0%, 35.5%, and 12.2% for meniscus height, depth, area, and angle,
      respectively. The intraclass correlations for these parameters were 0.605, 0.558,
      0.567, and 0.367, respectively. CONCLUSION: FD-OCT measures lower tear meniscus
      dimensions and area with higher between-visits reproducibility than previous OCT
      instruments. FD-OCT may be a useful way to measure dry eye severity and treatment
      effectiveness.

PMID- 19772268
TI  - Early laser photocoagulation treatment as an option in central serous
      chorioretinopathy.
AB  - BACKGROUND AND OBJECTIVE: To investigate the effect of early photocoagulation in
      central serous chorioretinopathy. PATIENTS AND METHODS: In a prospective study,
      15 consecutive patients with central serous chorioretinopathy and single leakage
      points were treated with photocoagulation between 2 days and 8 weeks after onset
      of symptoms. The main outcome measures were best-corrected visual acuity and
      metamorphopsias (Amsler grid) at months 1 and 4 compared with baseline. RESULTS:
      Mean visual acuity improved by 1.53 lines 1 month after treatment. The mean
      squares involved in the Amsler grid were reduced by 2.07 squares. No relapse
      occurred during the follow-up period. CONCLUSION: Considering the characteristics
      of individuals affected by central serous chorioretinopathy, a fast recovery
      would be advantageous. This study identified early laser photocoagulation in
      central serous chorioretinopathy as an effective treatment regarding resorption
      of subretinal fluid, recovery of visual acuity, and improvement of
      metamorphopsia.

PMID- 19772269
TI  - Transconjunctival sutureless vitrectomy for the treatment of vitreoretinal
      complications in patients with diabetes mellitus.
AB  - BACKGROUND AND OBJECTIVE: To compare the safety and effectiveness of 25-gauge
      transconjunctival sutureless vitrectomy (TSV) with conventional 20-gauge pars
      plana vitrectomy (PPV) for the treatment of vitreoretinal complications in
      patients with diabetic retinopathy. PATIENTS AND METHODS: Forty-five eyes of 44
      consecutive patients with diabetes mellitus who had undergone 25-gauge TSV for
      the treatment of vitreous hemorrhage, traction retinal detachment, or diabetic
      macular edema and 45 control patients with diabetes mellitus who had undergone
      conventional 20-gauge PPV were studied. RESULTS: The mean duration of surgery in
      the 25-gauge TSV group was statistically significantly shorter than that in the
      20-gauge PPV group. The mean visual acuity at both 1 week and 1 month after
      surgery was statistically significantly better in the 25-gauge TSV group than in
      the 20-gauge PPV group. Complications in the 25-gauge TSV group were similar to
      those in the 20-gauge PPV group. CONCLUSION: A shorter operation time and faster
      recovery of postoperative visual acuity were the main advantages of using 25
      gauge TSV. Despite its limitations, 25-gauge TSV can be safely used for the
      treatment of vitreoretinal complications in patients with diabetes mellitus.

PMID- 19772270
TI  - Intravitreal triamcinolone acetonide preceding photodynamic therapy for exudative
      age-related macular degeneration.
AB  - BACKGROUND AND OBJECTIVE: To evaluate the efficacy of intravitreal triamcinolone
      acetonide 1 week before photodynamic therapy (PDT) with verteporfin in the
      treatment of exudative age-related macular degeneration (AMD). PATIENTS AND
      METHODS: Retrospective chart review of 70 eyes of 66 consecutive patients who
      were treated with intravitreal triamcinolone acetonide followed by standard PDT 1
      week later. Group 1 consisted of 42 eyes that received one or more previous
      treatments with PDT alone and responded poorly. Group 2 consisted of 28 eyes that
      had never received PDT. RESULTS: No statistically significant change in mean
      visual acuity was seen during the follow-up period for either group. At 12
      months, 90% of group 1 eyes and 80% of group 2 eyes lost less than 2 lines of
      Snellen visual acuity. A mean of 1.24 additional PDT sessions were required in
      group 1 eyes and 1.04 additional sessions in group 2 eyes during the follow-up
      period. CONCLUSION: In eyes with exudative AMD, intravitreal triamcinolone
      acetonide preceding PDT with verteporfin results in stabilization of visual
      acuity and a decreased need for re-treatments with PDT. This regimen may be
      superior to PDT monotherapy.

PMID- 19772271
TI  - Effectiveness of laser photocoagulation in clinically significant macular edema
      with focal versus diffuse parafoveal thickening on optical coherence tomography.
AB  - BACKGROUND AND OBJECTIVE: To evaluate whether increased foveal thickness in
      clinically significant diabetic macular edema responds differently to modified
      focal/grid laser photocoagulation in the setting of focal versus diffuse
      parafoveal thickening as defined by optical coherence tomography (OCT) criteria.
      PATIENTS AND METHODS: The medical records of patients undergoing macular laser
      procedures for clinically significant diabetic macular edema were retrospectively
      reviewed. OCT, demographic, and clinical data were recorded for 62 consecutive
      eyes with clinically significant diabetic macular edema and foveal thickening (>
      230 microns). Diffuse parafoveal thickening was defined as having all four
      parafoveal OCT quadrants greater than 300 microns, whereas focal thickening was
      defined as having fewer than four quadrants greater than 300 microns. RESULTS:
      Mean foveal thickness decreased from 331 to 311 microns with relatively stable
      visual acuity (20/54 vs 20/51) after a single laser treatment session. The
      diffuse parafoveal edema subgroup (24 eyes) had a mean foveal thickness change
      from 383 to 366 microns (P = .47) and mildly decreased visual acuity (20/62 vs
      20/69). The focal parafoveal edema subgroup (38 eyes) experienced statistically
      significant foveal thinning from 299 to 276 microns (P = .018) and mildly
      improved visual acuity (20/48 to 20/43). CONCLUSION: Increased foveal thickening
      associated with clinically significant diabetic macular edema responds more
      favorably to modified focal/grid laser photocoagulation in the setting of focal
      parafoveal edema by OCT criteria. Statistically significant foveal thinning
      occurred following treatment in the focal group (P = .018) but not the diffuse
      group (P = .47). Furthermore, eyes with focal parafoveal edema experienced a more
      beneficial visual acuity response than those with diffuse edema (P = .049).

PMID- 19772273
TI  - Ciliary sulcus Ahmed Glaucoma Valve tube placement in neovascular glaucoma.
AB  - A 61-year-old woman presented with severe ocular pain 3 months after cataract
      extraction with intraocular lens placement. After performing a thorough
      ophthalmic examination, it was determined that neovascular glaucoma was present.
      The patient underwent implantation of an Ahmed valve (New World Medical, Inc.,
      Rancho Cucamonga, CA) with tube placement into the ciliary sulcus and received
      1.25 mg of bevacizumab intracamerally. The patient's iris neovascularization
      resolved and the patient maintained stable intraocular pressures without any
      major complications 6 months after surgery. Tube placement of an Ahmed valve into
      the ciliary sulcus can be a viable alternative for the maintenance of appropriate
      intraocular pressures in patients whose anatomy precludes standard anterior
      chamber or pars plana tube placement.

PMID- 19772272
TI  - High-resolution ocular imaging: combining advanced optics and microtechnology.
AB  - Recent developments in imaging technologies offer great potential for the
      assessment of retinal ganglion cell disorders, with particular relevance to
      glaucoma. In particular, advances in this field have allowed unprecedented in
      vivo access to the retinal layers, using many different properties of light to
      differentiate cellular structures. This article is a summary of currently
      available and investigational advanced, high-resolution imaging technologies and
      their potential applications to glaucoma. It represents the topics of discussion
      at the annual Optic Nerve Rescue and Restoration Think Tank, sponsored by The
      Glaucoma Foundation, entitled "High Resolution Imaging of the Eye: Advanced
      Optics, Microtechnology and Nanotechnology" and held in New York, New York,
      September 28-29, 2007.

PMID- 19772274
TI  - Hyphema following selective laser trabeculoplasty.
AB  - Selective laser trabeculoplasty is an effective means of lowering intraocular
      pressure in patients with open-angle glaucoma with a low risk of complications.
      The authors report a case of hyphema noted 3 days after selective laser
      trabeculoplasty in a 77-year-old woman with primary open-angle glaucoma. Her
      intermittent use of oral nonsteroidal anti-inflammatory medications and chronic
      topical nonsteroidal anti-inflammatory use may have been a contributing risk
      factor.

PMID- 19772275
TI  - Complete ring cyst of iris pigment epithelium documented by ultrasound
      biomicroscopy.
AB  - The authors report a complete ring cyst of the iris pigment epithelium confirmed
      by ultrasound biomicroscopy. In this case, ultrasound biomicroscopy effectively
      excluded the differential diagnoses of ring melanoma of the iris and multiple
      separate cysts of the iris pigment epithelium.

PMID- 19772276
TI  - Retinal vasculopathy in Fanconi anemia.
AB  - The authors present a case of Fanconi anemia with bilateral rapid onset retinal
      neovascularization and vitreous hemorrhage. The patient developed branch retinal
      vein occlusion in the left eye complicated by vitreous hemorrhage and was treated
      conservatively with intravitreal hyaluronidase injection. He declined vitrectomy
      and his visual acuity deteriorated to no perception of light. On follow-up, the
      right eye was noted to have clinical and angiographic evidence of sheathed
      vessels, an isolated large frond of neovascularization associated with areas of
      capillary nonperfusion. Panretinal photocoagulation and vitrectomy were performed
      with stabilization of vasculopathy and visual acuity. This case illustrates rapid
      onset peripheral occlusive vasculopathy with an atypical large isolated frond of
      neovascularization in a patient with Fanconi anemia resulting in blindness in one
      eye. Patients with Fanconi anemia would benefit from close and regular
      ophthalmological review.

PMID- 19772277
TI  - Surgical repair of iatrogenic macular hole secondary to vitrectomy for long
      standing traumatic retinal detachment.
AB  - The authors describe the successful surgical repair of an iatrogenic macular
      hole. A 38-year-old woman underwent pars plana vitrectomy with a belt buckle and
      membrane peeling for long-standing total traumatic retinal detachment. Although
      retinal reattachment was achieved, a macular hole was detected postoperatively.
      The hole was initially monitored for 2 months to allow for spontaneous closure;
      however, it enlarged from 440 to 710 microm. Best-corrected visual acuity was
      20/400. Silicone-oil removal was performed along with dye-assisted internal
      limiting membrane peeling and gas tamponade. Closure of the macular hole was
      observed 1 month after treatment. Visual acuity improved to 20/120 by the last
      follow-up examination 1 year after treatment.

PMID- 19772278
TI  - Macular star secondary to nasal branch retinal vein occlusion.
AB  - An 83-year-old woman affected by nasal branch retinal vein occlusion with macular
      star underwent treatment with intravitreal triamcinolone acetonide injection
      followed by laser treatment addressed to the leaking vascular lesions. Visual
      acuity improved from 20/200 to 20/40 with a remarkable reduction of the macular
      exudates and resolution of dye leakage on fluorescein angiography over a 2-year
      follow-up. Nasal branch retinal vein occlusion may rarely occur with macular
      edema and macular star. Intravitreal triamcinolone acetonide injection and laser
      treatment of the leaking vascular lesions can result in visual function
      improvement over a 2-year follow-up.

PMID- 19772279
TI  - Phenotypic heterogeneity and lesion size measurements in Stargardt macular
      dystrophy.
AB  - Fundus autofluorescence has been used in Stargardt macular dystrophy and fundus
      flavimaculatus to better understand disease status and progression. Fundus
      autofluorescence images delineate atrophic regions with great clarity and high
      contrast. The authors investigated whether fundus autofluorescence images
      revealed more atrophy than color fundus photographs by studying a family of three
      siblings with long-standing disease that demonstrated a heterogeneous fundus
      appearance. Findings on fundus autofluorescence were compared with color fundus
      photographs and fluorescein images. Optical coherence tomography images were also
      analyzed. Areas of atrophic lesions were measured and compared on fundus
      autofluorescence and color fundus photographs. Autofluorescence images delineated
      atrophic regions more clearly than color fundus photographs. However, the
      measured areas of atrophy were only modestly larger in fundus autofluorescence
      images than in color fundus photographs. The optical coherence tomography images
      showed severe outer retinal atrophy and loss of foveal contour.

PMID- 19772280
TI  - Retinal arteriolar macroaneurysm and congenital retinal macrovessel.
AB  - Variations in the morphology of the aneurysm and its serosanguineous
      complications serve to make a retinal arteriolar macroaneurysm, a common
      masquerading entity, particularly if it is accompanied by another un-associated
      retinal vascular abnormality. The authors present a patient who had an unusually
      large retinal arteriolar macroaneurysm in conjunction with a congenital retinal
      macrovessel.

PMID- 19772281
TI  - Ultra-high resolution spectral domain optical coherence tomography of traumatic
      maculopathy.
AB  - The authors describe a patient who suffered traumatic maculopathy following blunt
      trauma to the eye with commotio retinae, subretinal and preretinal hemorrhage,
      traumatic macular hole, and outer retinal and retinal pigment epithelium
      disruption. Serial imaging with commercially available and ultra-high resolution
      spectral domain optical coherence tomography characterized the evolution of the
      injury.

PMID- 19772282
TI  - Klebsiella pneumoniae endophthalmitis secondary to liver abscess presenting as
      acute iridocyclitis.
AB  - A 51-year-old man presented with acute iridocyclitis with no evidence of vitritis
      on B-scan that progressed to endogenous endophthalmitis. Systemic work-up
      revealed a large liver abscess. Urine, blood, liver abscess, and vitreous
      aspirate cultures all grew Klebsiella pneumoniae. The eye was enucleated
      secondary to severe pain from neovascular glaucoma and loss of vision.

PMID- 19772283
TI  - Implementing a structured oral examination into a residency program: a follow-up
      report.

PMID- 19772284
TI  - Analysis of intact glucuronides and sulfates of serotonin, dopamine, and their
      phase I metabolites in rat brain microdialysates by liquid chromatography-tandem
      mass spectrometry.
AB  - A method for the analysis of intact glucuronides and sulfates of common
      neurotransmitters serotonin (5-HT) and dopamine (DA) as well as of 5-hydroxy-3
      indoleacetic acid (5-HIAA), 3,4-dihydroxyphenylacetic acid (DOPAC), and
      homovanillic acid (HVA) in rat brain microdialysates by liquid chromatography
      tandem mass spectrometry (LC-MS/MS) was developed. Enzyme-assisted synthesis
      using rat liver microsomes as a biocatalyst was employed for the production of 5
      HT-, 5-HIAA-, DOPAC-, and HVA-glucuronides for reference compounds. The sulfate
      conjugates were synthesized either chemically or enzymatically using a rat liver
      S9 fraction. The LC-MS/MS method was validated by determining the limits of
      detection and quantitation, linearity, and repeatability for the quantitative
      analysis of 5-HT and DA and their glucuronides, as well as of 5-HIAA, DOPAC, and
      HVA and their sulfate-conjugates. In this study, 5-HT-glucuronide was for the
      first time detected in rat brain. The concentration of 5-HT-glucuronide (1.0-1.7
      nM) was up to 2.5 times higher than that of free 5-HT (0.4-2.1 nM) in rat brain
      microdialysates, whereas the concentration of DA-glucuronide (1.0-1.4 nM) was at
      the same level or lower than the free DA (1.2-2.4 nM). The acidic metabolites of
      neurotransmitters, 5-HIAA, HVA, and DOPAC, were found in free and sulfated form,
      whereas their glucuronidation was not observed.

PMID- 19772285
TI  - Asymmetric carbon-carbon bond formation gamma to a carbonyl group: phosphine
      catalyzed addition of nitromethane to allenes.
AB  - A chiral phosphine catalyzes the addition of a carbon nucleophile to the gamma
      position of an electron-poor allene (amide-, ester-, or phosphonate-substituted),
      in preference to isomerization to a 1,3-diene, in good ee and yield. This
      strategy provides an attractive method for the catalytic asymmetric gamma
      functionalization of carbonyl (and related) compounds.

PMID- 19772286
TI  - Simultaneous and label-free determination of wild-type and mutant p53 at a single
      surface plasmon resonance chip preimmobilized with consensus DNA and monoclonal
      antibody.
AB  - Simultaneous determination of wild-type and total p53 proteins (wild-type and
      mutant combined) present in cancer cell lysates has been performed with a dual
      channel surface plasmon resonance (SPR) instrument. To achieve specificity, each
      channel of the SPR chip was modified with a consensus double-stranded (ds-) DNA
      and a monoclonal antibody. The high affinity of the consensus ds-DNA to the wild
      type p53 and the antibody to total p53 results in remarkably low detection levels
      (10.6 and 1.06 pM for the wild-type and total p53, respectively). The difference
      between the SPR signals reveals the extent of p53 mutation, which is indicative
      of cancer development. The SPR signals increase with the p53 concentration across
      a wide range (from low picomolar to nanomolar levels) that amply encompasses the
      typical cellular p53 concentrations. The applicability of the method to real
      sample analysis has been demonstrated with the comparative analyses of normal and
      cancer cell lysates. The normal cell samples all displayed significantly higher
      levels of wild-type p53. In contrast, elevated levels of mutant p53 were observed
      from the cancer cell lysates. In comparison with enzyme-linked immunosorbant
      assay (ELISA), SPR obviates the need of a second antibody labeled with an enzyme
      in the "sandwich enzyme immunoassay" format and is capable of real-time
      monitoring of the binding events. Thus, SPR could potentially serve as an
      attractive technique for rapid, sensitive, reliable, and label-free cancer
      diagnoses.

PMID- 19772287
TI  - p38alpha mitogen-activated protein kinase inhibitors: optimization of a series of
      biphenylamides to give a molecule suitable for clinical progression.
AB  - p38alpha MAP kinase is a key anti-inflammatory target for rheumatoid arthritis,
      influencing biosynthesis of pro-inflammatory cytokines TNFalpha and IL-1beta at a
      translational and transcriptional level. In this paper, we describe how we have
      optimized a series of novel p38alpha/beta inhibitors using crystal structures of
      our inhibitors bound to p38alpha, classical medicinal chemistry, and modeling of
      virtual libraries to derive a molecule suitable for progression into clinical
      development.

PMID- 19772289
TI  - Potent and selective steroidal inhibitors of 17beta-hydroxysteroid dehydrogenase
      type 7, an enzyme that catalyzes the reduction of the key hormones estrone and
      dihydrotestosterone.
AB  - 17beta-Hydroxysteroid dehydrogenase type 7 (17beta-HSD7) catalyzes the reduction
      of estrone (E(1)) into estradiol (E(2)) and of dihydrotestosterone (DHT) into
      5alpha-androstane-3beta,17beta-diol (3beta-diol), therefore modulating the level
      of mitogenic estrogens and androgens in humans. By classical and parallel
      chemistry, we generated several 4-methyl-4-aza-5alpha-androstane derivatives
      differing in their C-17 substituent: 17beta-formamide, 17beta-benzamide, and
      17beta-tertiary amine. Best candidates in each category had demonstrated good
      inhibitory potency toward the conversion of E(1) into E(2) (IC(50) = 189-451 nM)
      and also toward the conversion of DHT into 3beta-diol (69-91% at 3 microM).
      Inhibition assays with 17beta-HSD1, 17beta-HSD5, 5alpha-reductase (5alpha-R) 1
      and 5alpha-R2 revealed that 17beta-HSD7 inhibitors with a 4-methyl-4-aza nucleus
      were also able to inhibit 5alpha-Rs but not the other enzymes tested. Two 4-aza
      5alpha-androstane inhibitors were, however, selective and still showed good
      inhibition of 17beta-HSD7. First selective and efficient inhibitors of 17beta
      HSD7 are now available for additional mechanistic and therapeutic studies.

PMID- 19772291
TI  - Electrically Controlling and Monitoring InP Nanowire Growth from Solution.
AB  - Indium phosphide nanowires are of significant technological interest for
      applications ranging from single junction solar cells to high speed electronics.
      However, the efficient placement and integration of nanowires into devices
      remains a significant challenge. Here we extend the technique of electrically
      controlled solution-liquid-solid (EC-SLS) catalytic nanowire growth to indium
      phosphide. We are able to control the amount of nanowire growth by varying the
      bias voltage between the electrodes in solution, and to monitor nanowire bridging
      across the electrodes by recording the conductivity as a function of growth time.
      The as-grown indium phosphide nanowires exhibit n-type conductivity as was
      determined by the in situ integration of nanowires into a field effect transistor
      geometry. The ability to monitor nanowire growth and electrically control
      nanowire placement are valuable tools for fabricating nanowire devices. The EC
      SLS process has the potential to aid in the fabrication of nanowire devices that
      could find applications in nanoelectronics, and as electrodes in solar cells and
      batteries.

PMID- 19772290
TI  - Nanoscale arrangement of apoptotic ligands reveals a demand for a minimal lateral
      distance for efficient death receptor activation.
AB  - Cellular apoptosis, the prototype of programmed cell death, can be induced by
      activation of so-called death receptors. Interestingly, soluble and membrane
      bound members of death receptor ligands can differentially activate their
      receptors. Using the death receptor ligand tumor necrosis factor (TNF) presented
      on a surface in a nanoscaled pattern with spacings between 58 and 290 nm, we
      investigated its requirements for spatial arrangement and motility to efficiently
      activate TNF receptor (TNFR)1 and TNFR2 as well as its chimeras TNFR1-Fas and
      TNFR2-Fas. We show that the mere mechanical fixation of TNF is insufficient to
      efficiently activate TNFR2 that is responsive to only the membrane bound form of
      TNF but not its soluble form. Rather, an additional stabilization of TNFR2(-Fas)
      by cluster formation seems to be mandatory for efficient activation. In contrast,
      TNFR1(-Fas) is strongly activated by TNF spaced within up to 200 nm distances,
      whereas larger spacings of 290 nm fails completely. Furthermore, unlike for
      TNFR2(-Fas) no dose-response relationship to increasing distances of
      nanostructured ligands could be observed for TNFR1-(Fas), suggesting that
      compartmentalization of the cell membrane in confinement zones of approximately
      200 nm regulates TNFR1 activation.

PMID- 19772292
TI  - Electron energy-loss spectroscopy (EELS) of surface plasmons in single silver
      nanoparticles and dimers: influence of beam damage and mapping of dark modes.
AB  - We demonstrate the use of a scanning transmission electron microscope (STEM)
      equipped with a monochromator and an electron energy loss (EEL) spectrometer as a
      powerful tool to study localized surface plasmons in metallic nanoparticles. We
      find that plasmon modes can be influenced by changes in nanostructure geometry
      and electron beam damage and show that it is possible to delineate the two
      effects through optimization of specimen preparation techniques and acquisition
      parameters. The results from the experimental mapping of bright and dark plasmon
      energies are in excellent agreement with the results from theoretical modeling.

PMID- 19772293
TI  - Discovery of a new class of protein farnesyltransferase inhibitors in the
      arylthiophene series.
AB  - Screening of the ICSN chemical library led to the discovery of 3-(4-chlorophenyl)
      4-cyano-5-thioalkylthiophene 2-carboxylic acids as potent farnesyltransferase
      inhibitors. Enzymatic kinetic studies showed that this original FTI series
      belongs to the CaaX competitive inhibitor class. Preliminary SAR studies allowed
      us to improve the IC50 from 110 to 7.5 nM.

PMID- 19772294
TI  - Synthesis and herbicidal activity of isoindoline-1,3-dione substituted
      benzoxazinone derivatives containing a carboxylic ester group.
AB  - A carboxylic ester group was introduced to three series of isoindolinedione
      substituted benzoxazinone derivatives. Some of these analogues exhibited good
      herbicidal activities, and the injury symptoms against weeds included leaf
      cupping, crinkling, bronzing, and necrosis, typical of protox inhibitor
      herbicides. Structurally, they were classified as Chemical Group A (4-carboxylic
      ester group-6-isoindolinyl-benzoxazinones), B (4-carboxylic ester group-7
      isoindolinyl-benzoxazinones), and C (4-carboxylic ester group-6-
      tetrahydroisoindolinyl-benzoxazinones). All of the tested compounds were
      structurally confirmed by (1)H NMR, IR, mass spectroscopy, and elemental
      analysis. Preliminary bioassay data of these three classes of compounds showed
      that, in general, the order of the herbicidal effectiveness is C > A > B. Several
      of the lead compounds, for example, C10 (methyl 2-(6-(1,3-dioxo-4,5,6,7
      tetrahydro-1H-isoindol-2(3H)-yl)-7-fluoro-2-methyl-3-oxo-2H-benzo[b][1,4] oxazin
      4(3H)-yl) propano-ate), C12 (ethyl 2-(6-(1,3-dioxo-4,5,6,7-tetrahydro-1H-isoindol
      2(3H)-yl)-7-fluoro-2- methyl-3-oxo-2H-benzo[b][1,4]oxazin-4(3H)-yl) propanoate),
      and C13 (ethyl 2-(6-(1,3-dioxo-4,5,6,7-tetrahydro-1H-isoindol-2(3H)-yl)-7-fluoro
      2-methyl-3-oxo-2H-benzo-[b][1,4]oxazin-4(3H)-yl) butanoate), exhibited greater
      than 80% control at 75 g a.i./ha in both pre- and postemergence treatments
      against dicotyledonous weeds, such as Abutilon theophrasti Medic, Chenopodium
      album L., and Amaranthus ascendens L., and monocotyledon weeds, such as Digitaria
      sanguinalis L., Echinochloa crus-galli L., and Setaria viridis L. On the basis of
      advanced screening tests and crop selectivity, compounds C10, C12, and C13 are
      safer to crops than flumioxazin. Compounds C10, C12, and C13 are potent to
      develop as pre-emergent herbicides used in peanut, soybean, maize, and cotton
      fields.

PMID- 19772295
TI  - Potent inhibitors of beta-tryptase and human leukocyte elastase based on the
      MCoTI-II scaffold.
AB  - MCoTI-II is a member of a class of microproteins known as cyclotides that possess
      a macrolactam-cystine knot scaffold imparting exceptional physiological stability
      and structural rigidity. Modification of residues in the active loop and
      engineered truncations have resulted in MCoTI-II analogues that possess potent
      activity against two therapeutically significant serine proteases: beta-tryptase
      and human leukocyte elastase. These results suggest that MCoTI-II is a versatile
      scaffold for the development of protease inhibitors against targets in
      inflammatory disease.

PMID- 19772296
TI  - Acrylamide formed at physiological temperature as a result of asparagine
      oxidation.
AB  - Acrylamide is a probable human carcinogen that is neurotoxic to both humans and
      animals. It is known to be formed during cooking of foods at temperatures higher
      than 120 degrees C. The present study demonstrates that acrylamide can also be
      formed at physiological conditions (37 degrees C, pH 7.4) when asparagine is
      incubated in the presence of hydrogen peroxide (H(2)O(2)). The formation of
      acrylamide under these conditions is dependent on the incubation time and the
      concentration of H(2)O(2). Thus, the results raise the question of the possible
      endogenous formation of acrylamide in pathological conditions that are associated
      with long-term oxidative stress. Further studies are therefore warranted to
      clarify the possible endogenous formation of acrylamide and its significance in
      chronic conditions that are known to be associated with oxidative stress.

PMID- 19772297
TI  - Heads and tails: simultaneous exposed and buried interface imaging of monolayers.
AB  - We have simultaneously imaged the chemically bound head groups and exposed tail
      groups in bicomponent alkanethiolate self-assembled monolayers on Au{111} with
      molecular resolution. This has enabled us to resolve the controversy of scanning
      tunneling microscopy image interpretation and to measure the molecular polar tilt
      and azimuthal angles. Our local measurements demonstrate that ordered domains
      with different superstructures also have varied buried sulfur head group
      structures.

PMID- 19772298
TI  - An intramolecular O-N migration reaction on gold surfaces: toward the preparation
      of well-defined amyloid surfaces.
AB  - Amyloids are a family of self-aggregating proteins implicated in various central
      nervous system disorders, including Alzheimer's disease (AD). It is thought that
      prefibrillar soluble forms of amyloid peptides, including oligomers, may be the
      main pathogenic factor in AD. Herein we describe the fabrication of well-defined,
      functionalized, monomeric beta-amyloid peptide surfaces for studying protein
      protein interactions. We first prepared a nonaggregating analogue of the beta
      amyloid peptide and then attached it to a gold surface covered with a self
      assembled monolayer (SAM) of alkanethiols. After attachment, the native form of
      the beta-amyloid peptide (Abeta40) was obtained by surface-level intramolecular O
      N migration. The surface was characterized by atomic force microscopy (AFM) and
      self-assembled monolayer for matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry (SAMDI-TOF MS). The interaction between the surface
      bound Abeta40 and monoclonal anti-Abeta40 antibody was tracked by AFM and
      chemiluminescence, which revealed that the Abeta40 was attached mainly in its
      monomeric form and that the protein-protein complex was assembled on the surface.
      Last, we used a proteomics approach to demonstrate the specificity of the Abeta40
      functionalized surface in surface-binding experiments employing serum amyloid P
      (SAP) and bovine serum albumin (BSA).

PMID- 19772299
TI  - Theoretical study on the reaction of ground state cyano radical with propylene in
      Titan's atmosphere.
AB  - The bimolecular reaction of ground state cyano radical with propylene under the
      condition of single collision is investigated by combining ab initio electronic
      structure calculations for predicting reaction paths and RRKM theory to yield
      rate constant for each path. The isomerization and dissociation channels for each
      of the seven collision complexes are characterized by utilizing the unrestricted
      B3LYP/cc-pVTZ level of theory and the CCSD(T)/cc-pVTZ calculations. Sifting with
      the facilitation of RRKM rate constants through web of ab initio paths composed
      of 8 collision complexes, 37 intermediates, and 12 H-, 23 H(2)-, 3 HCN-, and 4
      CH(3)-dissociated products, we identify the most probable paths down to 7-9
      species at collisions energies of 0 and 5 kcal/mol as the reaction mechanisms.
      The rate equations of the reaction mechanisms are solved numerically such that
      the concentration evolutions for all species involved are obtained. This study
      predicts that CN + C(2)H(3)CH(3) reaction via any of the seven collision complex,
      c1-c5, c7, and c8, would produce p1(CH(3)CHCHCN) + H, p2(CH(2)CHCH(2)CN) + H, and
      mostly p43(vinyl cyanide) + CH(3) for collision energy within 0-5 kcal/mol. In
      addition to the insertion mechanism through collision complex, the direct H
      abstraction of propylene by CN radical might occur. Our investigation indicates
      that the barrierless and exoergic CN(X(2)Sigma(+)) + C(2)H(3)CH(3)(X(1)A')
      reaction would be an efficient route for the p1, p2, and p43, and likely HCN
      formation in cold molecular clouds and in the atmosphere of Saturn's satellite
      Titan.

PMID- 19772288
TI  - In situ imaging of metals in cells and tissues.

PMID- 19772300
TI  - Effects of pH on the Rieske protein from Thermus thermophilus: a spectroscopic
      and structural analysis.
AB  - The Rieske protein from Thermus thermophilus (TtRp) and a truncated version of
      the protein (truncTtRp), produced to achieve a low-pH crystallization condition,
      have been characterized using UV-visible and circular dichroism spectroscopies.
      TtRp and truncTtRp undergo a change in the UV-visible spectra with increasing pH.
      The LMCT band at 458 nm shifts to 436 nm and increases in intensity. The increase
      at 436 nm versus pH can be fit using the sum of two Henderson-Hasselbalch
      equations, yielding two pK(a) values for the oxidized protein. For TtRp, pK(ox1)
      = 7.48 +/- 0.12 and pK(ox2) = 10.07 +/- 0.17. For truncTtRp, pK(ox1) = 7.87 +/-
      0.17 and pK(ox2) = 9.84 +/- 0.42. The shift to shorter wavelength and the
      increase in intensity for the LMCT band with increasing pH are consistent with
      deprotonation of the histidine ligands. A pH titration of truncTtRp monitored by
      circular dichroism also showed pH-dependent changes at 315 and 340 nm. At 340 nm,
      the fit gives pK(ox1) = 7.14 +/- 0.26 and pK(ox2) = 9.32 +/- 0.36. The change at
      315 nm is best fit for a single deprotonation event, giving pK(ox1) = 7.82 +/-
      0.10. The lower wavelength region of the CD spectra was unaffected by pH,
      indicating that the overall fold of the protein remains unchanged, which is
      consistent with crystallographic results of truncTtRp. The structure of truncTtRp
      crystallized at pH 6.2 is very similar to TtRp at pH 8.5 and contains only subtle
      changes localized at the [2Fe-2S] cluster. These titration and structural results
      further elucidate the histidine ligand characteristics and are consistent with
      important roles for these amino acids.

PMID- 19772301
TI  - Synthesis of cyclopentitols by ring-closing approaches.

PMID- 19772303
TI  - Au(I)-catalyzed cycloisomerization reaction of amide- or ester-tethered 1,6
      enynes to bicyclo[3.2.0]hept-6-en-2-ones.
AB  - The cycloisomerization reaction of N-allyl-2-(2'-arylethyne-2-yl)amides or
      allylic 2-alkynoates in the presence of cationic triphenylphosphinegold(I)
      produced bicyclo[3.2.0]hept-6-en-2-ones under mild conditions. Computational
      investigations with a density functional theory (DFT) revealed that a stepwise 6
      endo-dig cyclization of 1,6-enyne systems, followed by a skeletal rearrangement
      to form bicyclo[3.2.0]hept-6-en-2-one species represents the most probable
      reaction pathway. This can be further supported by employing N-(1',1'-dimethyl-1
      propen-3-yl)-2-(1''-phenylethyne-2''-yl)amide as a substrate, which exclusively
      produced 4-phenyl-5-(prop-1-en-2-yl)-5,6-dihydropyridino-2(1H)-one unambiguously
      via 6-endo-dig cyclization. Theoretical calculations suggest both an aryl group
      at the terminal alkyne and a keto carbonyl at the C(5) position of the 1,6-enyne
      system play a complementary role for the reactivity.

PMID- 19772302
TI  - Multifunctional nanoparticles for combined doxorubicin and photothermal
      treatments.
AB  - To facilitate combined doxorubicin and photothermal treatments, we developed
      doxorubicin-loaded poly(lactic-co-glycolic acid)-gold half-shell nanoparticles
      (DOX-loaded PLGA-Au H-S NPs) by depositing Au films on DOX-loaded PLGA NPs. As
      the PLGA NPs biodegraded, DOX was released, and heat was locally generated upon
      near-infrared (NIR) irradiation due to NIR resonance of DOX-loaded PLGA H-S NPs.
      Compared with chemotherapy or photothermal treatment alone, the combined
      treatment demonstrated a synergistic effect, resulting in higher therapeutic
      efficacy and shorter treatment times. Since our NPs selectively deliver both heat
      and drug to tumorigenic regions, they may improve the therapeutic effectiveness
      with minimal side effects.

PMID- 19772304
TI  - Simulation of the electromechanical behavior of multiwall carbon nanotubes.
AB  - The enormous potential of carbon nanotubes (CNTs) as primary components in
      electronic devices and NEMS necessitates the understanding and predicting of the
      effects of mechanical deformation on electron transport in CNTs. In principle,
      detailed atomic/electronic calculations can provide both the deformed
      configuration and the resulting electrical transport behavior of the CNT.
      However, the computational expense of these simulations limits the size of the
      CNTs that can be studied with this technique, and a direct analysis of CNTs of
      the dimension used in nanoelectronic devices seems prohibitive at the present.
      Here a computationally effective mixed finite element (FE)/tight-binding (TB)
      approach able to simulate the electromechanical behavior of CNT devices is
      presented. The TB code is carefully designed to realize orders-of-magnitude
      reduction in computational time in calculating deformation-induced changes in
      electrical transport properties of the nanotubes. The FE-TB computational
      approach is validated in a simulation of laboratory experiments on a multiwall
      CNT and then used to demonstrate the role of the multiwall structure in providing
      robustness to conductivity in the event of imposed mechanical deformations.

PMID- 19772305
TI  - Carbon nanotubes are able to penetrate plant seed coat and dramatically affect
      seed germination and plant growth.
AB  - Carbon nanotubes (CNTs) were found to penetrate tomato seeds and affect their
      germination and growth rates. The germination was found to be dramatically higher
      for seeds that germinated on medium containing CNTs (10-40 mug/mL) compared to
      control. Analytical methods indicated that the CNTs are able to penetrate the
      thick seed coat and support water uptake inside seeds, a process which can affect
      seed germination and growth of tomato seedlings.

PMID- 19772307
TI  - Readily prepared 3-chloro-1-(phenylthio)propene, a versatile three-carbon
      annulating agent.
AB  - 3-Chloro-1-(phenylthio)propene, simply generated by chlorination of commercial
      allyl phenyl sulfide, is a versatile 3-carbon annulating agent for ketones and
      phenols.

PMID- 19772306
TI  - Crack-free 3D hybrid microstructures from photosensitive organosilicates as
      versatile photonic templates.
AB  - We fabricated diamond-like microstructures from epoxy-functionalized cyclohexyl
      polyhedral oligomeric silsesquioxanes (POSS) through four-beam interference
      lithography. The 3D structure was maintained when calcined at a temperature up to
      1100 degrees C, and crack-free samples over a large area ( approximately 5 mm in
      diameter) were obtained when the POSS films were heated at 500 degrees C under an
      Ar environment or treated with a low intensity oxygen plasma. In the latter, the
      volume fraction of the 3D porous structures could be fine-tuned by plasma etching
      time and power. Both Fourier transform infrared (FT-IR) spectroscopy and energy
      dispersive X-ray (EDX) spectroscopy analysis suggested that the presence of
      carbon materials in the films enhanced the crack resistance of 3D POSS structures
      treated under Ar or oxygen plasma. Since POSS and its derivatives could be easily
      removed by HF solution at room temperature, we demonstrated high fidelity
      replication of the 3D porous structures to biocompatible poly(glycidyl
      methacrylate) (PGMA) and elastomeric poly(dimethylsiloxane) (PDMS). Importantly,
      the whole fabrication process (template fabrication, infiltration, and removal)
      was carried out at room temperature. Finally, we illustrated the application of
      3D PDMS film as a reversible and repeatable color-changing, flexible photonic
      crystal.

PMID- 19772308
TI  - Asymmetric copper-catalyzed propargylic substitution reaction of propargylic
      acetates with enamines.
AB  - Enamines served as carbon-nucleophiles for the first time in the Cu-catalyzed
      asymmetric propargylic substitution reaction of propargylic acetates, providing
      corresponding chiral beta-ethynyl-substituted ketones in high yields and in good
      to high enantioselectivity.

PMID- 19772309
TI  - Proton NMR study of Cr-Co heterometallic wheel complexes.
AB  - (1)H NMR spectra of the paramagnetic heterometallic complexes of general formula
      [cation][Cr(7)CoF(8)(O(2)C(t)Bu)(16)] have been recorded. The NMR spectra have
      allowed the investigation of the structure of these complexes in solution. These
      experiments show that the complexes are stable and maintain the solid state
      structure in solution, retaining the protonated amine in the cavity of the
      heterometallic ring.

PMID- 19772310
TI  - A new peroxide fragmentation: efficient chemical generation of (1O2) in organic
      media.
AB  - Monoactivated derivatives of 1,1-dihydroperoxides undergo an unprecedented base
      promoted fragmentation to efficiently generate singlet oxygen (1O2) in anhydrous
      organic solvents.

PMID- 19772311
TI  - Inhibition of aggregation of [Pd]-bacteriochlorophyllides in mesoporous silica.
AB  - Aggregation is a major factor affecting the photophysical properties of
      chlorophylls. For two [Pd]-bacteriochlorophyll derivatives that are currently
      under clinical testing as sensitizers for photodynamic therapy, aggregation
      control in aqueous solution has been studied with folded-sheet mesoporous silica
      (FSM) of different pore sizes (20, 45, 83 A) and with detergent (Triton X-100).
      With both the moderately polar WST09 and the highly polar WST11, no pigment
      oligomers were formed in FSM, and the monomer-dimer equilibrium was shifted
      toward the monomer with decreasing pore diameter.

PMID- 19772312
TI  - Bis-N-annulated quaterrylenebis(dicarboximide) as a new soluble and stable near
      infrared dye.
AB  - A new ladder-type bis-N-annulated quaterrylenebis(dicarboximide) (1) was
      synthesized, and it exhibits excellent solubility in common organic solvents,
      high molar absorptivity, and good stability. Moreover, it absorbs and emits light
      in the near-IR spectral region with a high fluorescence quantum yield. All these
      properties qualify it as a promising NIR dye for many applications.

PMID- 19772313
TI  - An extremely facile synthesis of furans, pyrroles, and thiophenes by the
      dehydrative cyclization of propargyl alcohols.
AB  - Furans, pyrroles, and thiophenes are efficiently prepared by gold-catalyzed
      dehydrative cyclizations of readily available, heteroatom-substituted propargylic
      alcohols. The reactions are rapid, high-yielding, and procedurally simple, giving
      essentially pure aromatic heterocycles in minutes under open-flask conditions
      with catalyst loadings as low as 0.05 mol %.

PMID- 19772314
TI  - A ratiometric fluorescent chemodosimeter with selective recognition for sulfite
      in aqueous solution.
AB  - A fluorescent chemodosimeter containing a guanidiniocarbonylpyrrole and a 9
      (aminomethyl)anthracene moiety has been synthesized. The sensor exhibits
      ratiometric fluorescence changes for SO(3)(2-) over other anions in 90%
      water/DMSO. The interesting ratiometric fluorescent changes for SO(3)(2-) are
      attributed to the fluorescence resonance energy transfer (FRET) and the SO(3)(2-)
      complex induced photochemical reaction.

PMID- 19772315
TI  - Viscosity of dilute model bead arrays at low shear: inclusion of short range
      solute-solvent interactions.
AB  - The intrinsic viscosity, [eta], of certain polymer-solvent systems, such as
      alkanes in benzene, are "anomalous" in the sense that [eta] for low molecular
      weight fractions are low and in certain cases negative (Dewan, K. K.; Bloomfield,
      V. A.; Berget, P. G.; J. Phys. Chem. 1974, 75, 3120). In this work, the theory of
      the viscosity of a dilute suspension of macromolecules at low shear is formulated
      that accounts for possible solute-solvent interactions. In doing so, we show that
      negative intrinsic viscosities are possible and are able to reproduce quite well
      the known length dependence of [eta] for alkanes in benzene. The coarse grained,
      solvent continuum, bead model developed here is an extension of previous work
      (Allison, S. A.; Pei, H. J. Phys. Chem. B 2009, 113, 8056). Following Fixman
      (Fixman, M. J. Chem. Phys. 1990, 92, 6858), we assume that solute-solvent
      interactions are short-range in character and can be separated from long-range
      hydrodynamic interactions between different beads. These interactions are
      accounted for by introducing three adjustable parameters specific to the
      transport of small "monomeric" solutes in the solvent of interest. Long range
      hydrodynamic interactions are accounted for to order a(J)(2)/r(IJ)(3) (a(J) is a
      bead radius and r(IJ) is an interbead distance). In modeling a macromolecule as
      an arbitrary array of N beads, the transport of the array is examined numerically
      in 5 different elementary shear fields. The most computationally demanding
      component of the procedure involves the inversion of a 12N by 12N matrix. In the
      present work, we restrict ourselves to systems with a maximum N of about 100. Our
      procedure is first applied to short rods and rings of from 2 to 10 beads which
      can be compared with independent results from the literature. Agreement is found
      to be better than 5%. Modeling macromolecules as wormlike chains, the procedure
      is then applied first to duplex DNA and then to alkanes in benzene. In both
      cases, it is possible to obtain excellent agreement between modeling and
      experiment.

PMID- 19772316
TI  - Interactions and aggregations in aqueous and brine solutions of
      poly(diallydimethylammonium chloride)/sodium bis(2-ethylhexyl) sulfosuccinate.
AB  - The interactions between the anionic surfactant sodium bis(2-ethylhexyl)
      sulfosuccinate (AOT) and the polycation poly(diallydimethylammonium chloride)
      (PDDAC), the aggregations of AOT and PDDAC-bound AOT in PDDAC/AOT aqueous
      solutions, and the influence of salt on the interactions and aggregations have
      been studied by isothermal titration calorimetry (ITC), dynamic light scattering
      (DLS), and negative staining transmission electron microscopy (TEM). The
      adsorptions of AOT onto PDDAC and the formations of PDDAC-bound AOT micelles,
      free AOT micelles, and AOT vesicles were examined, and the corresponding critical
      concentrations were determined. Combining calculations of thermodynamic
      parameters with the above three experimental techniques, it was shown that the
      micellization of free AOT is driven by entropy gain, while the adsorption of AOT
      onto PDDAC and the micellization of PDDAC-bound AOT are driven by both enthalpy
      and entropy. It was also found that addition of salt enhances the binding of AOT
      onto PDDAC through the ion exchange and favors the formations of PDDAC/AOT
      micelles, free AOT micelles, and free AOT vesicles but prevents the transition of
      PDDAC/AOT micelles to the vesicles. Thermodynamic analysis suggested that the
      adsorption of AOT onto PDDAC and the micellization of PDDAC/AOT in PDDAC/AOT
      brine solutions are different in mechanism compared with that in corresponding
      aqueous solutions.

PMID- 19772317
TI  - Ligand-enhanced reduction of perchlorate in water with heterogeneous Re-Pd/C
      catalysts.
AB  - New bimetallic heterogeneous catalysts for the reduction of perchlorate in water
      with dihydrogen have been prepared in two ways: (1) by impregnating 5 wt % Pd on
      activated carbon powder with one of the complexes trans-[ReO(2)(py-X)(4)](+) (py
      X = 4-substituted pyridine; X = H, Me, OMe, NMe(2)) or (2) by adsorbing
      perrhenate onto the Pd/C powder in the presence of the pyridine ligand under a
      hydrogen atmosphere. Both sets of catalysts are highly active at pH 2.7-3.0
      (HCl), with observed rates increasing with varying X in the order H < Me < OMe <
      NMe(2), which supports a rate-determining oxygen atom transfer reaction involving
      the Re(V) centers. However, the materials prepared by method (1) show evidence of
      facile formation of perrhenate from handling under ambient conditions. A system
      prepared by method (2) with 2 equiv of dimethylaminopyridine per Re is especially
      active and stable up to pH 4.5.

PMID- 19772318
TI  - Electronic coulombic coupling of excitation-energy transfer in xanthorhodopsin.
AB  - Electronic coupling of excitation-energy transfer (EET) in a retinal (RET)
      protein, xanthorhodopsin (xR), was studied theoretically. The protein,
      functioning as a light driven proton pump, contains a carotenoid antenna,
      salinixanthin (SXN), to collect light energy for an RET chromophore through EET.
      The pseudo-Coulombic interaction (PCI) between the donor SXN and the acceptor RET
      molecules was calculated by a transition density fragment interaction (TDFI)
      method, which overcomes difficulty arising in the evaluation of PCI in xR by a
      conventional dipole-dipole (dd) method, at the ab initio TDDFT/SAC-CI level of
      theory. The result nicely agrees with the experimentally observed PCI. To examine
      the correlation between the SXN-RET alignment and the EET efficiency, we computed
      PCIs for SXN conformations that are virtually generated around the protein. The
      calculation shows that the optimal SXN alignment for the maximally tuned
      efficiency of EET is attained in the native xR. PCI in another retinal protein,
      archaerhodopsin-2, which also binds a carotenoid but lacks EET activity, was also
      evaluated. The computed PCI is negligibly small, well explaining the lack of EET
      efficiency.

PMID- 19772319
TI  - Spin trapping of radicals other than the *OH radical upon reduction of the
      anticancer agent tirapazamine by cytochrome P450 reductase.
AB  - The radical species produced following one-electron reduction of tirapazamine (3
      amino-1,2,4-benzotriazine 1,4-dioxide, TPZ) by cytochrome P(450) reductase
      enriched microsomes have been investigated using electron paramagnetic resonance
      (EPR) spectroscopy. Spin trapping with 5,5'-dimethylpyrroline 1-N-oxide (DMPO)
      gave a composite spectrum of a carbon-centered radical and the well-known DMPO-OH
      adduct. Using (17)O-labeled water resulted in a change in the EPR spectrum to
      that of DMPO-(17)OH, indicating that this radical species is formed with solvent
      involvement and not from release of a (*)OH radical from one-electron-reduced
      TPZ. Furthermore, using the closely related spin trap 5-diethoxyphosphoryl-5
      methylpyrroline N-oxide (DEPMPO), which is less prone to oxidation than DMPO,
      gave only a carbon-centered radical spectrum without any involvement of a (*)OH
      radical. Reduction of a more soluble analogue of TPZ, in redox equilibrium with
      its 1-oxide derivative, led to spin trapping of both a carbon-centered radical
      and a nitrogen-centered radical by N-tert-butyl-alpha-phenylnitrone (PBN). The
      multicentered nature of this nitrogen-centered radical spectrum provides support
      for the formation of a benzotriazinyl radical following one-electron reduction of
      this class of bioreductive drug.

PMID- 19772320
TI  - Efficient near-IR hyperthermia and intense nonlinear optical imaging contrast on
      the gold nanorod-in-shell nanostructures.
AB  - New gold nanorod (Au NR)-in-shell nanostructures were developed to be more
      efficacious than Au NRs in near-IR (NIR) hyperthermia and nonlinear optical
      imaging contrast. Au NR-in-shell nanostructures are composed of an intact Au NR
      in a Au/Ag nanoshell. These nanostructures have a broad, intense absorption band
      that extends from 400 nm to 900 nm in the NIR. They are more efficient and
      efficacious than Au NRs with respect to in vitro hypothermia performance. Au NR
      in-shell-labeled cancer cells were destroyed using continuous-wave NIR radiation
      with 50% less laser power than needed for Au NRs. Noticeably, the area of the
      destroyed cells was significantly larger than the size of the laser irradiation
      beam; in contrast, the destroyed area was usually restricted to the size of the
      laser beam spot when Au NRs were used. With their extraordinarily broad and
      strong surface plasmon resonance band, Au NR-in-shell nanostructures efficiently
      augmented several multiphoton nonlinear processes as well. The multiphoton
      emission spectrum covered almost the entire visible wavelength. The yield of the
      multiphoton signals of Au NR-in-shell nanostructures was on average 55 times
      larger than that of Au NRs. In vitro images of cancer cells targeted by Au NR-in
      shell nanostructures revealed a stronger multiphoton contrast than those targeted
      by Au NRs.

PMID- 19772321
TI  - Enhancement of the encapsulation and transmembrane permeation of isoflavone
      containing red clover extracts in phospholipid-based microemulsions using
      different extraction processes.
AB  - Several isoflavone-enriched red clover extracts (RCE) prepared by using solid- or
      liquid-phase extraction or a combination of both were studied for their
      encapsulation into a phospholipid-based microemulsion system. The optimization
      process with regard to the bioactive ingredient-encapsulated amounts and
      transmembrane efficiency of various RCE micelles was demonstrated. The results
      indicated that the encapsulated amounts of isoflavones in RCE-encapsulated
      microemulsions (ME) of ME-RC5, ME-RC6, and ME-RC7 were increased by >10-fold when
      compared with that of the raw red clover extracts. Comparison of the permeability
      coefficient K(p) of the formononetin among the ME-RCs from the in vitro skin
      permeation study showed that ME-RC5 significantly exhibited the least
      permeability, whereas ME-RC6 exhibited enhanced permeability after two-stage
      solid-phase extraction, indicating the potential role of the matrix material as a
      barrier or enhancer in the transmembrane study.

PMID- 19772322
TI  - Roasted coffees high in lipophilic antioxidants and chlorogenic acid lactones are
      more neuroprotective than green coffees.
AB  - Oxidative stress is involved in many neurodegenerative processes leading to age
      related cognitive decline. Coffee, a widely consumed beverage, is rich in many
      bioactive components, including polyphenols with antioxidant potential. In this
      study, regular and decaffeinated samples of both roasted and green coffee all
      showed high hydrophilic antioxidant activity in vitro, whereas lipophilic
      antioxidant activities were on average 30-fold higher in roasted than in green
      coffee samples. In primary neuronal cell culture, pretreatment with green and
      roasted coffees (regular and decaffeinated) protected against subsequent H(2)O(2)
      induced oxidative stress and improved neuronal cell survival (green coffees
      increased neuron survival by 78%, compared to 203% by roasted coffees). All
      coffee extracts inhibited ERK1/2 activation, indicating a potential attenuating
      effect in stress-induced neuronal cell death. Interestingly, only roasted coffee
      extracts inhibited JNK activation, evidencing a distinctive neuroprotective
      benefit. Analysis of coffee phenolic compounds revealed that roasted coffees
      contained high levels of chlorogenic acid lactones (CGLs); a significant
      correlation between CGLs and neuroprotective efficacy was observed (R(2) = 0.98).
      In conclusion, this study showed that roasted coffees are high in lipophilic
      antioxidants and CGLs, can protect neuronal cells against oxidative stress, and
      may do so by modulation of the ERK1/2 and JNK signaling pathways.

PMID- 19772323
TI  - Genetically encoding N(epsilon)-methyl-L-lysine in recombinant histones.
AB  - Lysine methylation is an important post-translational modification of histone
      proteins that defines epigenetic status and controls heterochromatin formation, X
      chromosome inactivation, genome imprinting, DNA repair, and transcriptional
      regulation. Despite considerable efforts by chemical biologists to synthesize
      modified histones for use in deciphering the molecular role of methylation in
      these phenomena, no general method exists to synthesize proteins bearing
      quantitative site-specific methylation. Here we demonstrate a general method for
      the quantitative installation of N(epsilon)-methyl-L-lysine at defined positions
      in recombinant histones and demonstrate the use of this method for investigating
      the methylation dependent binding of HP1 to full length histone H3 monomethylated
      on K9 (H3K9me1). This strategy will find wide application in defining the
      molecular mechanisms by which histone methylation orchestrates cellular
      phenomena.

PMID- 19772324
TI  - Phenyl radical-induced damage to dipeptides.
AB  - Laser-induced acoustic desorption (LIAD) incorporated with Fourier transform ion
      cyclotron resonance mass spectrometry (FT-ICR) has been utilized to investigate
      phenyl radical-induced damage to dipeptides in the gas phase. On the basis of the
      product branching ratios measured for the reactions of two different positively
      charged phenyl radicals with 17 different dipeptides, the overall order of
      susceptibility to attack of the different sites in the dipeptides was determined
      to be heteroaromatic side chain approximately = S atom in SCH(3) group > H atom
      in SH group > H atom in CH group > aromatic side chain > S atom in SH group >
      NH(2) in side chain > N-terminal NH(2) > COOH in side chain approximately = C
      terminal COOH. The amino acid sequence also influences the selectivity of these
      reactions. As expected, the ability of a phenyl radical to damage dipeptides
      increases as the electrophilicity of the phenyl radical increases.

PMID- 19772325
TI  - CuI nanoparticles for C-N and C-O cross coupling of heterocyclic amines and
      phenols with chlorobenzenes.
AB  - Employing CuI nanoparticles as an efficient catalyst for the cross-coupling
      reactions of various N/O nucleophilic reagents with aryl chlorides could be
      successfully carried out under mild conditions in the absence of both the ligands
      and strong bases. A variety of products including N-arylimidazoles and aryl
      ethers were synthesized in good to excellent yields.

PMID- 19772326
TI  - Design and synthesis of highly luminescent near-infrared-emitting water-soluble
      CdTe/CdSe/ZnS core/shell/shell quantum dots.
AB  - Applications of water-dispersible near-infrared (NIR)-emitting quantum dots (QDs)
      have been hampered by their instability and low photoluminescence (PL)
      efficiencies. In this paper, water-soluble highly luminescent NIR-emitting QDs
      were developed through constructing CdTe/CdSe/ZnS core/shell/shell nanostructure.
      The CdTe/CdSe type-II structure yields the QDs with NIR emission. By varying the
      size of CdTe cores and the thickness of the CdSe shell, the emission wavelength
      of the obtained nanostructure can span from 540 to 825 nm. In addition, the
      passivation of the ZnS shell with a substantially wide bandgap confines the
      excitons within the CdTe/CdSe interface and isolates them from the solution
      environment and consequently improves the stability of the nanostructure,
      especially in aqueous media. An effective shell-coating route was developed for
      the preparation of CdTe/CdSe core/shell nanostructures by selecting capping
      reagents with a strong coordinating capacity and adopting a low temperature for
      shell deposition. An additional ZnS shell was deposited around the outer layer of
      CdTe/CdSe QDs to form the core/shell/shell nanostructure through the
      decomposition of single molecular precursor zinc diethyldithiocarbamate in the
      crude CdTe/CdSe reaction solution. The water solubilization of the initially oil
      soluble CdTe/CdSe/ZnS QDs was achieved through ligand replacement by 3
      mercaptopropionic acid. The as-prepared water-soluble CdTe/CdSe/ZnS QDs possess
      PL quantum yields as high as 84% in aqueous media, which is one of the best
      results for the luminescent semiconductor nanocrystals.

PMID- 19772328
TI  - Wetting and superhydrophobicity.
AB  - This article is written to serve as an introduction to the topic of "Wetting and
      Superhydrophobicity" and to give some perspective for the papers that follow.
      This area of research that impacts and overlaps many fields of science and
      technology has been identifiable for centuries, but has gained considerable
      traction in the past decade.

PMID- 19772327
TI  - Molecular pockets derived from cholic acid as chemosensors for metal ions.
AB  - Molecular pockets in the form of a tripod made of cholic acid were found to be
      able to solubilize pyrene in polar media as a result of the facial amphiphilicity
      of bile acids. The trimer containing 1,2,3-triazole groups can complex with heavy
      metal ions, as clearly shown by electron paramagnetic resonance spectroscopy.
      Both the metal cation and the pyrene molecule can be brought close together in
      the cavity formed by the cholic acid trimer, resulting in significantly improved
      efficiency for fluorescence quenching of pyrene. The decrease of fluorescence
      intensity can be used for the detection of heavy metal ions, and the detection
      limit is about 1 microM in water, suggesting the usefulness of such molecules as
      chemosensors for such metal ions. A different trimer without the coordinating
      triazole groups is shown to shield pyrene away from metal ions, causing a much
      reduced fluorescence quenching.

PMID- 19772329
TI  - Hierarchical assembly of ZnO nanostructures on SnO(2) backbone nanowires: low
      temperature hydrothermal preparation and optical properties.
AB  - Hierarchical nanostructures with SnO(2) backbones and ZnO branches are
      successfully prepared in a large scale by combining the vapor transport and
      deposition process (for SnO(2) nanowires) and a hydrothermal growth (for ZnO).
      The ZnO nanorods grow epitaxially on the SnO(2) nanowire side faces mainly with a
      four-fold symmetry. The number density and morphology of the secondary ZnO can be
      tailored by changing the precursor concentration, reaction time, and by adding
      surfactants. Photoluminescence (PL) properties are studied as a function of
      temperature and pumping power. Such hybrid SnO(2)-ZnO nanostructures show an
      enhanced near-band gap emission compared with the primary SnO(2) nanowires. Under
      the optical excitation, a UV random lasing is observed which originates from the
      hierarchically assembled ZnO branches. These three-dimensional nanostructures may
      have application potentials as chemical sensors, battery electrodes, and
      optoelectronic devices.

PMID- 19772330
TI  - Self-assembled monolayers of double-chain disulfides of adenine on Au: an IR-UV
      sum-frequency generation spectroscopic study.
AB  - We have synthesized double-chain disulfides of adenine with different chain
      lengths (n = 2, 4, 5, 9, and 10) and studied their self-assembled monolayers
      (SAM) on gold surface by IR-UV doubly resonant sum frequency generation
      spectroscopy with the help of DFT calculation. A versatile way to investigate the
      orientation angle of functional groups of SAMs and their surface coverage has
      been demonstrated. It was revealed that the IR dipoles of the band at around 1630
      cm(-1), which were almost parallel to the long molecular axis of the adenine
      ring, were less tilted with respect to the substrate surface in the SAMs with
      longer chains (n = 9 and 10) in comparison to those with shorter chains (n = 2,
      4, and 5).

PMID- 19772331
TI  - Stimuli-sensitive assemblies of homopolymers.
AB  - Two homopolymers assemble into nanoparitcles in a common solvent of water through
      ionic complexation. These nanoparticles reversibly and rapidly respond to both pH
      and temperature, and are particularly promising as intelligent systems.

PMID- 19772332
TI  - Electronic hyperpolarizabilities for donor-acceptor molecules with long
      conjugated bridges: calculations versus experiment.
AB  - We investigate the molecular first hyperpolarizability (beta) for donor/acceptor
      (D/A) substituted pi-conjugated organic molecules with different D/A groups and
      pi-systems (including up to eight pi-bonds). The results of the MP2 and density
      functional theory (PBE0, BMK, M05, M05-2X) calculations are compared to those
      obtained from experimental data. The goal of this study is to select a protocol
      with optimal quality/cost ratio to be used for systematic prediction of molecular
      nonlinear optical (NLO) properties. This goal is closely related to the way in
      which theoretical betas are compared to experimental ones and to the accuracy and
      consistency of experimental hyperpolarizabilities used to test theoretical
      predictions. We found that two DFT functionals with the larger fraction of
      Hartree-Fock exchange (BMK and especially M05-2X) provide the best agreement to
      the experiment, comparable to that of the MP2 method. Due to high computational
      cost of MP2 method, we recommend to use the M05-2X functional as a tool for
      systematic prediction of molecular hyperpolarizabilities.

PMID- 19772333
TI  - Thermochemistry of bithiophenes and thienyl radicals. A calorimetric and
      computational study.
AB  - The relative stabilities of 2,2'- and 3,3'-bithiophenes were evaluated by
      experimental thermochemistry and the results compared with data obtained from
      state of the art calculations, which were also extended to 2,3'-bithiophene. The
      standard (p degrees = 0.1 MPa) molar enthalpies of formation of crystalline 2,2'
      bithiophene and 3,3'-bithiophene were calculated from the standard molar energies
      of combustion, in oxygen, to yield CO(2) (g) and H(2)SO(4) x 115 H(2)O, measured
      by rotating-bomb combustion calorimetry at T = 298.15 K. The vapor pressures of
      these two compounds were measured as a function of temperature by Knudsen
      effusion mass-loss technique. The standard molar enthalpies of sublimation, at T
      = 298.15 K, were derived from the Clausius-Clapeyron equation. The experimental
      values were used to calculate the standard (p(o) = 0.1 MPa) enthalpies of
      formation of the title compounds in the gaseous phase; the results were analyzed
      and interpreted in terms of enthalpic increments and molecular structure.
      Standard ab initio molecular orbital calculations at the G3(MP2)//B3LYP level
      were performed. Enthalpies of formation, using homodesmotic reactions, were
      calculated and compared with experimental data. The computational study was also
      extended to the isomeric compound 2,3'-bithiophene. Detailed inspections of the
      molecular and electronic structures of the compounds studied were carried out.
      Finally, bond dissociation enthalpies (BDE) and enthalpies of formation of
      thienyl radicals were also computed.

PMID- 19772334
TI  - Analysis of bacterial lipid-linked oligosaccharide intermediates using porous
      graphitic carbon liquid chromatography-electrospray ionization mass spectrometry:
      heterogeneity in the polyisoprenyl carrier revealed.
AB  - N-glycosylation of proteins is recognized as one of the most common post
      translational modifications. It was believed that N-glycosylation occurred
      exclusively in eukaryotes until the recent discovery of the general protein
      glycosylation pathway (Pgl) in Campylobacter jejuni, which has similarities to
      the eukaryotic system and adds proteins en bloc from a lipid carrier to a protein
      acceptor. In addition to N-linked glycans, a number of pathogenic bacteria such
      as Pseudomonas aeruginosa and Neisseria species have been shown to O-glycosylate
      their proteins through polyisoprene-linked intermediates. To date, most
      techniques to analyze lipid-linked oligosaccharides (LLOs) of these pathways
      involve the use of radiolabels and chromatographic separation. With the
      increasing frequency of reports of bacterial protein glycosylation that proceed
      through lipid-mediated steps, there is a need for technologies capable of
      characterizing these newly described bacterial systems as well as eukaryotic
      pathways from biologically relevant samples in an accurate, rapid, and cost
      effective manner. In this paper, a new glycomics strategy based on porous
      graphite carbon (PGC) liquid chromatography mass spectrometry (LC-MS) was devised
      and validated on the C. jejuni N-glycan pathway. Lipid-linked oligosaccharide
      intermediates of the Pgl pathway from crude lipid extracts were separated using
      online chromatography on a capillary PGC column with a chloroform gradient. By
      exploiting the retention properties of hydrophobic and polar analytes on PGC,
      baseline separation of LLOs with minor changes in oligosaccharide structure and
      polyisoprene chain length was obtained. This method is capable of analyzing low
      levels of LLOs (from approximately 10(6) bacterial cells) and distinguishing the
      LLOs that differ by as little as one monosaccharide or polyisoprene unit.
      Furthermore, we have demonstrated for the first time that oligosaccharides of the
      C. jejuni Pgl pathway are assembled on different polyisoprenes, e. g. C(45),
      C(60), and apparent hydroxylated forms, in addition to those previously reported
      (i.e., C(50) and C(55)). The hydroxylated forms of the LLOs are believed to be an
      intermediate in the degradation of accumulated LLOs for polyisoprene carrier
      recycling.

PMID- 19772336
TI  - Novel one-pot three- and pseudo-five-component reactions: synthesis of
      functionalized benzo[g]- and dihydropyrano[2,3-g]chromene derivatives.
AB  - A novel and efficient method has been developed for the synthesis of highly
      functionalized benzo[g]- and dihydropyrano[2,3-g]chromene derivatives via
      addition and subsequently cyclization of 2-hydroxynaphthalene-1,4-dione or 2,5
      dihydroxycyclohexa-2,5-diene-1,4-dione to the condensation product of an aldehyde
      with malononitrile in the presence of a catalytic amount of Et(3)N in CH(3)CN at
      ambient temperature. The procedures are very facile. The products can be obtained
      with simple filtration in high yields, and no more purification is needed. These
      compounds are closely related to ring systems such as beta-lapachone, alpha
      xiloidone, lambertellin, pyranokunthone B, and WS-5995A, which have a broad
      spectrum of biological activities.

PMID- 19772337
TI  - Carboxyl BODIPY dyes from bicarboxylic anhydrides: one-pot preparation, spectral
      properties, photostability, and biolabeling.
AB  - New fluorescent dyes based on 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY)
      and functionalized with a free carboxyl group have been conveniently synthesized
      from pyrroles and dicarboxylic anhydrides in one-pot reactions. Their spectral
      properties in different solvents showed little effect of solvatochromism (<10
      nm). The methyl groups on the BODIPY skeleton benefit the fluorescence quantum
      yields (Phi(f) up to 0.80 in water) but affect the photostability of the dyes.
      Photooxidation and photodegradation experiments suggest that dyes 1a and 2a
      exhibit excellent photostability, especially in water, and several factors were
      taken into account to elucidate the experimental phenomena. Dyes 1c and 2c,
      derived from 1a and 2a via the esterification of NHS (N-hydroxysuccinimidyl
      ester), can be easily acquired in high yields (>90%). Single crystal X-ray
      structures of dyes 2c and 3a are also obtained and discussed. The fluorescence
      labeling of BSA and followed prestaining method for gel electrophoresis of BSA
      demonstrate that the protein can be directly observed by naked eyes at as low as
      2 ng level under a normal UV fluorescence electrophorogram gel image system.

PMID- 19772339
TI  - Domino palladium-catalyzed Heck-intermolecular direct arylation reactions.
AB  - A domino palladium-catalyzed Heck-intermolecular direct arylation reaction has
      been developed, giving access to a variety of dihydrobenzofurans, indolines, and
      oxindoles. A variety of sulfur-containing heterocycles such as thiazoles,
      thiophenes, and benzothiophene can be employed as the direct arylation coupling
      partner in yields up to 99%.

PMID- 19772340
TI  - Electron-transfer processes in metal-free tetraferrocenylporphyrin. Understanding
      internal interactions to access mixed-valence States potentially useful for
      quantum cellular automata.
AB  - Redox properties of H(2)TFcP [TFcP(2-) = 5,10,15,20-tetraferrocenylporphyrin(2-)]
      were investigated using cyclic voltammetry, differential pulse voltammetry, and
      square-wave voltammetry methods in a large variety of solvents and electrolytes.
      When DMF, THF, and MeCN were used with TBAP as the supporting electrolyte, the
      first oxidation wave was assigned to a single four-electron oxidation process
      reflecting simultaneous oxidation of all iron(II) centers into iron(III) centers
      in H(2)TFcP. When an o-DCB (1,2-dichlorobenzene)/TBAP combination was used in
      electrochemical experiments, four ferrocene substituents underwent two very
      diffuse, "two-electron" stepwise oxidations. The use of a weakly coordinating
      TFAB ([NBu(4)][B(C(6)F(5))(4)]) electrolyte in o-DCB or DCM results in four
      single-electron oxidation processes for ferrocene substituents in which the first
      and second single-electron waves have a relatively large separation, while the
      second, third, and fourth oxidation processes are more closely spaced; similar
      results were observed when a DCM/TBAP system and an imidazolium cation-based
      ionic liquid ((bmim)Tf(2)N = N-butyl-N'-methylimidazolium
      bis(trifluoromethanesulfonyl)imide) were used. Spectroelectrochemical oxidation
      of H(2)TFcP in o-DCB or DCM with TFAB as the supporting electrolyte allowed for
      characterization of the mixed-valence [H(2)TFcP](+), [H(2)TFcP](2+), and
      [H(2)TFcP](3+) compounds by UV-vis spectroscopy in addition to the "all-Fe(III)"
      [H(2)TFcP](4+). The chemical oxidation of H(2)TFcP was tested using a variety of
      oxidants which resulted in formation of mixed-valence [H(2)TFcP](+) and
      [H(2)TFcP](2+) as well as [H(2)TFcP](4+), which were characterized by UV-vis-NIR,
      MCD, IR, Mossbauer, and XPS spectroscopy. The intervalence-charge-transfer bands
      observed in the near-IR region in [H(2)TFcP](+) and [H(2)TFcP](2+) complexes were
      analyzed using Hush formalism and found to be of class II (in Robin-Day
      classification) character with localized ferrous and ferric centers. Class II
      behavior of [H(2)TFcP](+) and [H(2)TFcP](2+) complexes was further confirmed by
      Mossbauer, IR, and XPS data.

PMID- 19772338
TI  - Conformational preferences of 1-amino-2-phenylcyclohexanecarboxylic acid, a
      phenylalanine cyclohexane analogue.
AB  - The intrinsic conformational preferences of the restricted phenylalanine analogue
      generated by including the alpha and beta carbon atoms into a cyclohexane ring (1
      amino-2-phenylcyclohexanecarboxylic acid, c(6)Phe) have been determined using
      quantum mechanical calculations. Specifically, the conformational profile of the
      N-acetyl-N'-methylamide derivative of the c(6)Phe stereoisomers exhibiting either
      a cis or a trans relative orientation between the amino and phenyl substituents
      has been analyzed in different environments (gas phase, chloroform, and aqueous
      solutions). Calculations were performed using B3LYP, MP2, and HF methods combined
      with the 6-31+G(d,p) and 6-311++G(d,p) basis sets, and a self-consistent reaction
      field (SCRF) method was applied to analyze the influence of the solvent. The
      amino acids investigated can be viewed as constrained phenylalanine analogues
      with a rigidly oriented aromatic side chain that may interact with the peptide
      backbone not only sterically but also electronically through the aromatic pi
      orbitals. Their conformational propensities have been found to be strongly
      influenced by the specific orientation of the aromatic substituent in each
      stereoisomer and the conformation adopted by the cyclohexane ring, as well as by
      the environment.

PMID- 19772341
TI  - Redox-active metallomacrocycles and cyclic metallopolymers: photocontrolled ring
      opening oligomerization and polymerization of silicon-bridged [1]ferrocenophanes
      using substitutionally-labile Lewis bases as initiators.
AB  - Irradiation of silicon-bridged [1]ferrocenophane [Fe(eta-C(5)H(4))(2)SiMe(2)] (1)
      in the presence of substitutionally labile Lewis bases such as 4,4'-dimethyl-2,2'
      bipyridine (Me(2)bpy) initiates ring-opening polymerization and oligomerization
      via cleavage of an iron-cyclopentadienyl bond. A distribution of cyclic
      polyferrocenylsilane c-PFS (PFS = [Fe(eta-C(5)H(4))(2)SiMe(2)](n)) and a series
      of cyclic oligomers (2(2)-2(7)) were isolated by column chromatography and fully
      characterized. Varying temperature and concentration were found to influence the
      molecular weight distribution and the ratio of polymer to oligomer products,
      enabling the formation of c-PFS with molecular weights >100 kDa. Cyclic polymer
      samples were found to possess lower hydrodynamic radii and viscosity and higher
      glass transition temperatures than those of their linear PFS counterparts (l-PFS)
      of comparable molecular weight. Compared with crystalline samples of l-PFS of
      similar molecular weights, c-PFS formed smaller spherulites, as observed by
      polarizing optical microscopy. While the wide-angle X-ray scattering (WAXS)
      patterns from lower molecular weight l-PFS were found to differ from those from
      higher molecular weight samples, those obtained for lower and higher molecular
      weight samples of c-PFS are identical and resemble diffraction patterns of high
      molecular weight l-PFS. The electrochemical behavior of each cyclic oligomer 2(2)
      2(7) was studied by cyclic and differential pulse voltammetry and was found to
      depend on whether the oligomer contains an odd or even number of ferrocene units.
      In contrast to linear analogs, two reversible redox processes of varying
      intensities were observed for cyclic oligomers containing an even number of iron
      centers, while three reversible redox processes of varying intensities were
      observed for cyclic oligomers containing an odd number of iron centers. As the
      oligomer chain length increased, the electrochemical behavior of all cyclic
      oligomers approached that of both cyclic and linear high molecular weight
      polymers.

PMID- 19772343
TI  - Dehydrocoupling reactions of borane-secondary and -primary amine adducts
      catalyzed by group-6 carbonyl complexes: formation of aminoboranes and borazines.
AB  - Photoirradiation of a solution of BH(3).NHR(2) (1a: R = Me, 1b: R = 1/2C(4)H(8),
      1c: R = 1/2C(5)H(10), 1f: R = Et) containing a catalytic amount of a group-6
      metal carbonyl complex, [M(CO)(6)] (M = Cr, Mo, W), led to dehydrogenative B-N
      covalent bond formation to produce aminoborane dimers, [BH(2)NR(2)](2) (2a-c, f),
      in high yield. During these reactions a borane sigma complex, [M(CO)(5)(eta(1)
      BH(3).NHR(2))] (3), was detected by NMR spectroscopy. Similar catalytic
      dehydrogenation of bulkier amineboranes, BH(3).NH(i)Pr(2) (1d) and BH(3).NHCy(2)
      (1e, Cy = cyclo-C(6)H(11)), afforded monomeric products BH(2) horizontal
      lineNR(2) (4d, e). The reaction mechanism of the dehydrocoupling was investigated
      by DFT calculations. On the basis of the computational study, we propose that the
      catalytic dehydrogenation reactions proceed via an intramolecular pathway and
      that the active catalyst is [Cr(CO)(4)]. The reaction follows a stepwise
      mechanism involving NH and BH activation. Dehydrocoupling of borane-primary amine
      adducts BH(3).NH(2)R (1g: R = Me, 1h: R = Et, 1i: R = (t)Bu) gave borazine
      derivatives [BHNR](3) (5g-i).

PMID- 19772342
TI  - Facile synthesis of polyester dendrimers from sequential click coupling of
      asymmetrical monomers.
AB  - Polyester dendrimers are attractive for in vivo delivery of bioactive molecules
      due to their biodegradability, but their synthesis generally requires multistep
      reactions with intensive purifications. A highly efficient approach to the
      synthesis of dendrimers by simply "sticking" generation by generation together is
      achieved by combining kinetic or mechanistic chemoselectivity with click
      reactions between the monomers. In each generation, the targeted molecules are
      the major reaction product as detected by matrix-assisted laser desorption
      ionization time-of-flight mass spectrometry (MALDI-TOF MS). The only separation
      needed is to remove the little unreacted monomer by simple precipitation or
      washing. This simple clicklike process without complicated purification is
      particularly suitable for the synthesis of custom-made polyester dendrimers.

PMID- 19772344
TI  - Effect of latitude and altitude on the terpenoid and soluble phenolic composition
      of juniper (Juniperus communis) needles and evaluation of their antibacterial
      activity in the boreal zone.
AB  - The demand for dry juniper (Juniperus communis) needles as a raw material for the
      food, pharmaceutical, and cosmetic industries has increased rapidly in recent
      years. Juniper needles are known to be rich in terpenoids and phenolics, but
      their chemical composition and antibacterial properties have not been well
      characterized. In this study, we describe the soluble phenolic and terpenoid
      composition of juniper needles collected in Finland (n = 125) and demonstrate
      that the concentration of these compounds clearly increased with latitude and
      altitude with, however, a stronger latitudinal effect (a higher content of
      monoterpenoids, proanthocyanidins, and flavonols in northern latitudes). Analysis
      of methanolic extracts showed quite good activity against both antibiotic
      sensitive and -resistant Staphylococcus aureus strains and suggested an important
      role of the soluble phenolic fraction. Finally, we demonstrate the relative lack
      of toxicity of juniper extracts on keratinocytes and fibroblastic cells, raising
      the possibility of their use in preventing bacterial skin infection.

PMID- 19772345
TI  - Isothermal amplification of genetically modified DNA sequences directly from
      plant tissues lowers the barriers to high-throughput and field-based genotyping.
AB  - DNA extractions are a major cost for high-throughput genotyping. The loop
      mediated isothermal amplification (LAMP) assay has been used for the detection of
      two genetically modified (GM) related sequences. The amplification of target DNA
      sequences from leaf and maize seed tissues prepared with minimum preparative
      treatment (disruption in water) demonstrates the ability of LAMP to work in
      conditions normally inhibitive to PCRs. The wide dynamic range of detection in
      these samples suggests that LAMP is highly sensitive even when the target is
      presented in such a crude form. LAMP offers a means of reducing genotyping costs
      as well as simplifying testing procedures.

PMID- 19772346
TI  - Investigation of N-aryl-3-alkylidenepyrrolinones as potential Niemann-Pick type C
      disease therapeutics.
AB  - A five-step synthesis of an array of N-aryl-3-alkylidenepyrrolinones, which are
      potential Niemann-Pick type C (NPC) disease therapeutics, is described. The
      synthetic route allows for the production of analogues, including photoaffinity
      and biotinylated derivatives. Compound 1a increased esterification by acyl
      coenzyme A:cholesteryl acyltransferase in NPC1 mutant cells. It also decreased
      LDL uptake and increased cholesterol efflux in both NPC1-deficient and normal
      cells.

PMID- 19772347
TI  - Microbial iron acquisition: marine and terrestrial siderophores.

PMID- 19772350
TI  - Electrochemistry and spectroscopy of organometallic terpyridine nickel complexes.
AB  - Organonickel complexes [(R'terpy)Ni(aryl)]X (R'terpy = derivatives of 2,2';6',2''
      terpyridine; aryl = 2,6-dimethylphenyl = Xyl or 2,4,6-trimethylphenyl = Mes; X =
      Br or PF(6)) have been investigated by multiple electrochemical methods as well
      as combined electrochemical/spectroscopic techniques (spectroelectrochemistry).
      Reversible electrochemical reduction fills successively pi* orbitals in the terpy
      ligand. Some of the occurring species were characterized spectroscopically (EPR
      and UV/vis/NIR spectroelectrochemistry). The presumably nickel-centered oxidation
      occurs irreversibly.

PMID- 19772348
TI  - The cis-(5R,6S)-thymine glycol lesion occupies the wobble position when
      mismatched with deoxyguanosine in DNA.
AB  - Oxidative damage to 5-methylcytosine in DNA, followed by deamination, yields
      thymine glycol (Tg), 5,6-dihydroxy-5,6-dihydrothymine, mispaired with
      deoxyguanosine. The structure of the 5R Tg.G mismatch pair has been refined using
      a combination of simulated annealing and isothermal molecular dynamics
      calculations restrained by NMR-derived distance restraints and torsion angle
      restraints in 5'-d(G(1)T(2)G(3)C(4)G(5)Tg(6)G(7)T(8)T(9)T(10)G(11)T(12))-3'.5'
      d(A(13)C(14)A(15)A(16)A(17)C(18)G(19)C(20)G(21)C(22)A(23)C(24))-3'; Tg = 5R Tg.
      In this duplex the cis-5R,6S:trans-5R,6R equilibrium favors the cis-5R,6S epimer
      [Brown, K. L., Adams, T., Jasti, V. P., Basu, A. K., and Stone, M. P. (2008) J.
      Am. Chem. Soc. 130, 11701-11710]. The cis-5R,6S Tg lesion is in the wobble
      orientation such that Tg(6) O(2) is proximate to G(19) N1H and Tg(6) N3H is
      proximate to G(19) O(6). Both Tg(6) and the mismatched nucleotide G(19) remain
      stacked in the helix. The Tg(6) nucleotide shifts toward the major groove and
      stacks below the 5'-neighbor base G(5), while its complement G(19) stacks below
      the 5'-neighbor C(20). In the 3'-direction, stacking between Tg(6) and the
      G(7).C(18) base pair is disrupted. The solvent-accessible surface area of the Tg
      nucleotide increases as compared to the native Watson-Crick hydrogen-bonded T.A
      base pair. An increase in T(2) relaxation rates for the Tg(6) base protons is
      attributed to puckering of the Tg base, accompanied by increased disorder at the
      Tg.G mismatch pair. The axial vs equatorial conformation of the Tg(6) CH(3) group
      cannot be determined with certainty from the NMR data. The rMD trajectories
      suggest that in either the axial or equatorial conformations the cis-5R,6S Tg
      lesion does not form strong intrastrand hydrogen bonds with the imidazole N7 atom
      of the 3'-neighbor purine G(7). The wobble pairing and disorder of the Tg.G
      mismatch correlate with the reduced thermodynamic stability of the mismatch and
      likely modulate its recognition by DNA base excision repair systems.

PMID- 19772349
TI  - A general and efficient approach for NMR studies of peptide dynamics in class I
      MHC peptide binding grooves.
AB  - T-Cell receptor recognition of peptides bound by major histocompatibility complex
      (MHC) proteins initiates a cellular immune response. Dynamics of peptides within
      MHC binding grooves can influence TCR recognition, yet NMR studies which could
      address this rigorously have been hindered by the expense of isotopically labeled
      peptides and the large size of peptide-MHC complexes. Here we describe a
      methodology for characterizing peptide dynamics within MHC binding grooves via
      NMR, using a biosynthetic approach for producing labeled peptide. With the Tax(11
      19) peptide bound to the human class I MHC HLA-A*0201, we demonstrate that
      peptide generated in this manner can be well characterized in MHC binding grooves
      by NMR, providing opportunities to more precisely study the role of peptide
      dynamics in TCR recognition. Demonstrating the utility of such studies, the data
      with the Tax(11-19) peptide indicate the presence of slow conformational exchange
      in the peptide, supporting an "induced-fit" style TCR binding mechanism.

PMID- 19772351
TI  - Ordering in a droplet of an aqueous suspension of single-wall carbon nanotubes on
      a solid substrate.
AB  - We report on a series of experiments on the aqueous, nematic liquid crystalline
      phase of single-wall carbon nanotubes (SWNTs) and their ordered assemblies on the
      solid substrates. The nanotubes were dispersed at a low concentration of
      isotropic phase, and the concentration was gradually increased by the controlled
      evaporation of water. In-situ isotropic-to-liquid crystalline phase transition
      via a biphasic region was observed during water evaporation. Drying on a
      substrate demonstrated the effect of surface fields on the order and alignment of
      SWNTs in the liquid suspension and the influence on the structure of the
      deposited nanotubes after evaporation.

PMID- 19772352
TI  - Effect of a domain-spanning disulfide on aminoacyl-tRNA synthetase activity.
AB  - Enzymes regulated by allostery undergo conformational rearrangement upon binding
      effector molecules. For modular proteins, a flexible interface may mediate
      reorientation of the protein domains and transmit binding events to activate
      catalysis at a distance. Aminoacyl-tRNA synthetases (aaRSs) that use tRNA
      anticodons as identity elements can be considered allosteric enzymes in which
      aminoacylation of the tRNA acceptor stem is enhanced upon anticodon binding. We
      reasoned that anticodon-triggered conformational change might be restricted upon
      introduction of a disulfide linkage near the core of an aaRS. Here we show that a
      double cysteine mutation engineered at the Escherichia coli MetRS domain
      interface spontaneously generates a disulfide linkage. This disulfide clamp has
      no effect on methionyl adenylate formation but reduces the level of tRNA(Met)
      aminoacylation approximately 2-fold. Activity is restored upon chemical reduction
      of the disulfide, demonstrating that E. coli MetRS requires a flexible interface
      domain for full catalytic efficiency.

PMID- 19772353
TI  - The anti-helminthic niclosamide inhibits Wnt/Frizzled1 signaling.
AB  - Wnt proteins bind to seven-transmembrane Frizzled receptors to mediate the
      important developmental, morphogenetic, and stem cell related tissue-regenerative
      effects of Wnt signaling. Dysregulated Wnt signaling is associated with many
      cancers. Currently, there are no drug candidates or even tool compounds that
      modulate Wnt-mediated receptor trafficking, and subsequent Wnt signaling. We
      examined libraries of FDA-approved drugs for their utility as Frizzled
      internalization modulators, employing a primary imaged-based GFP fluorescence
      assay that uses Frizzled1 endocytosis as the readout. We now report that the anti
      helminthic niclosamide, a drug used for the treatment of tapeworm, promotes
      Frizzled1 endocytosis, downregulates Dishevelled-2 protein, and inhibits Wnt3A
      stimulated beta-catenin stabilization and LEF/TCF reporter activity.
      Additionally, following niclosamide-mediated internalization, the Frizzled1
      receptor colocalizes in vesicles containing transferrin and agonist-activated
      beta(2)-adrenergic receptor. Therefore, niclosamide may serve as a negative
      modulator of Wnt/Frizzled1 signaling by depleting upstream signaling molecules
      (i.e., Frizzled and Dishevelled) and moreover may provide a valuable means of
      studying the physiological consequences of Wnt signaling.

PMID- 19772354
TI  - Molybdenum trafficking for nitrogen fixation.
AB  - The molybdenum nitrogenase is responsible for most biological nitrogen fixation,
      a prokaryotic metabolic process that determines the global biogeochemical cycles
      of nitrogen and carbon. Here we describe the trafficking of molybdenum for
      nitrogen fixation in the model diazotrophic bacterium Azotobacter vinelandii. The
      genes and proteins involved in molybdenum uptake, homeostasis, storage,
      regulation, and nitrogenase cofactor biosynthesis are reviewed. Molybdenum
      biochemistry in A. vinelandii reveals unexpected mechanisms and a new role for
      iron-sulfur clusters in the sequestration and delivery of molybdenum.

PMID- 19772355
TI  - Mutual exchange of kinetic properties by extended mutagenesis in two short LOV
      domain proteins from Pseudomonas putida.
AB  - We previously characterized a LOV protein PpSB2-LOV, present in the common soil
      bacterium Pseudomonas putida, that exhibits a plant phototropin LOV-like
      photochemistry [Krauss, U., Losi, A., Gartner, W., Jaeger, K. E., and Eggert, T.
      (2005) Phys. Chem. Chem. Phys. 7, 2804-2811]. Now, we have identified a second
      LOV homologue, PpSB1-LOV, found in the same organism with approximately 66%
      identical amino acids. Both proteins consist of a conserved LOV core flanked by
      short N- and C-terminal extensions but lack a fused effector domain. Although
      both proteins are highly similar in sequence, they display drastically different
      dark recovery kinetics. At 20 degrees C, PpSB2-LOV reverts with an average time
      constant of 137 s from the photoequilibrium to the dark state, whereas PpSB1-LOV
      exhibits an average dark recovery time constant of 1.48 x 10(5) s. Irrespective
      of the significant differences in their dark recovery behavior, both proteins
      showed nearly identical kinetics for the photochemically induced adduct
      formation. In order to elucidate the structural and mechanistic basis of these
      extremely different dark recovery time constants, we performed a mutational
      analysis. Six amino acids in a distance of up to 6 A from the flavin chromophore,
      which differ between the two proteins, were identified and interchanged by site
      directed mutagenesis. The amino acid substitution R66I located near the FMN
      phosphate in LOV domains was identified in PpSB1-LOV to accelerate the dark
      recovery by 2 orders of magnitude. Vice versa, the corresponding substitution
      I66R slowed down the dark recovery in PpSB2-LOV by a factor of 10. Interestingly,
      the interchange of the C-terminal extensions between the two proteins also had a
      pronounced effect on the dark recovery time constants, thus highlighting a
      coupling of these protein regions to the chromophore binding pocket.

PMID- 19772357
TI  - A direct white-light-emitting metal-organic framework with tunable yellow-to
      white photoluminescence by variation of excitation light.
AB  - A direct white-light metal-organic framework (MOF), [AgL](n) x nH(2)O (1, L = 4
      cyanobenzoate), obtained by the reaction of deprotonated 4-cyanobenzoic acid and
      AgNO(3) in water, was found to exhibit tunable yellow-to-white photoluminescence
      by variation of excitation light. Interestingly, the close pure white emission of
      1 has CIE-1931 chromaticity coordinates of (0.33, 0.34) when excited by 349-nm UV
      light, which is compatible to the light output of the deep UV LED.

PMID- 19772356
TI  - Branch-specific sialylation of IgG-Fc glycans by ST6Gal-I.
AB  - Sialylated forms of the Fc fragment of immunoglobulin G, produced by the human
      alpha2-6 sialyltransferase ST6Gal-I, were identified as potent anti-inflammatory
      mediators in a mouse model of rheumatoid arthritis and are potentially the active
      components in intravenous IgG anti-inflammatory therapies. The activities and
      specificities of hST6Gal-I are, however, poorly characterized. Here MS and NMR
      methodology demonstrates glycan modification occurs in a branch-specific manner
      with the alpha1-3Man branch of the complex, biantennary Fc glycan preferentially
      sialylated. Interestingly, this substrate preference is preserved when using a
      released glycan, suggesting that the apparent occlusion of glycan termini in Fc
      crystal structures does not dominate specificity.

PMID- 19772358
TI  - Microfluidic device for single-molecule experiments with enhanced photostability.
AB  - A microfluidic device made of polydimethylsiloxane (PDMS) addresses key
      limitations in single-molecule fluorescence experiments by providing high dye
      photostability and low sample sticking. Photobleaching is dramatically reduced by
      deoxygenation via gas diffusion through porous channel walls. Rapid buffer
      exchange in a laminar sheath flow followed by optical interrogation minimizes
      surface-sample contacts and allows the in situ addition and combination of other
      reagents.

PMID- 19772359
TI  - Unexpected formation of a cyclopentadienylruthenium alkoxycarbonyl complex with a
      coordinated C=C bond.
AB  - Reaction of (eta(5)-Ph(5)C(5))Ru(CO)(2)(Ot-Bu) with 5-hexen-2-ol produces two
      diastereomers of an alkoxycarbonyl complex having the double bond coordinated to
      ruthenium. The complexes were characterized by (1)H and (13)C NMR spectroscopy
      and in situ FT-IR measurements. The (13)C NMR carbonyl peaks of the complexes
      appear at 203.48, 203.55, and 204.0 ppm in a ratio of 1:1:2. IR peaks for CO and
      acyl were detected at 1982 (CO) and 1644 (acyl) cm(-1).

PMID- 19772360
TI  - pH-Induced aggregation of gold nanoparticles for photothermal cancer therapy.
AB  - We report a "smart" gold nanoparticle that is designed to aggregate in mild
      acidic intracellular environments by its hydrolysis-susceptible citraconic amide
      surface. With a relatively small size of 10 nm, the "smart" gold nanoparticles
      can be efficiently internalized into cancerous cells. Triggered by pH change, the
      nanoparticle surfaces are engineered to have both positive and negative charges.
      Electrostatic attractions between the nanoparticles can rapidly form aggregates
      inside the cells, and the aggregates accumulate as the exocytosis is blocked by
      the increased size. Endocytosis of gold nanoparticles and the aggregation are
      monitored real-time by dark field optical microscopy. The pH-induced formation of
      aggregates shifts the absorption to far-red and near-infrared. The absorption
      shift to longer wavelength is used for photothermal cancer therapy as it
      guarantees maximal tissue penetration for potential therapeutic applications. The
      gold nanoparticles show selective and efficient destruction of cancerous cells
      with an intensity threshold of 5 W/cm(2) to induce the thermal destruction. In
      the intensity range 5-13 W/cm(2), the circular area of damaged cells increases
      linearly with the irradiation power density. This shows a new proof-of-concept
      for photothermal cancer therapy that exploits collective plasmon modes of metal
      nanoparticles.

PMID- 19772361
TI  - Probing the dynamics of a protein hydrophobic core by deuteron solid-state
      nuclear magnetic resonance spectroscopy.
AB  - With the goal of investigating dynamical features of hydrophobic cores of
      proteins over a wide range of temperatures, the chicken villin headpiece
      subdomain protein (HP36) was labeled at a "single" site corresponding to any one
      of the two C(delta)D(3) groups of leucine-69, which is located in a key position
      of the core. The main techniques employed are deuteron NMR quadrupolar echo line
      shape analysis, and T(1Z) (Zeeman) and T(1Q) (quadrupolar order) relaxation
      experiments performed at 11.7 and 17.6 T over the temperature range of 112 to 298
      K. The experimental data are compared with computer simulations. The deuteron
      line shapes give an excellent fit to a three-mode motional model that consists of
      (a) fast three-site rotational jumps about the pseudo C(3) methyl spinning axis,
      (b) slower reorientation of the spinning axis, described by diffusion along a
      restricted arc, and (c) large angle jumps between traces of rotameric conformers.
      Relaxation behavior is described by a phenomenological distribution of activation
      energies for three-site hops at high temperatures that collapses to a single,
      distinctly smaller value for lower temperatures.

PMID- 19772362
TI  - Synthetic chloride channel regulates cell membrane potentials and voltage-gated
      calcium channels.
AB  - Synthetic ion channels are of great interest in mimicking the biological
      functions of natural ion channels. Although many synthetic ion channels could
      selectively mediate ion transport across lipid bilayer membranes, the biological
      roles played by these synthetic channels in living systems remain essentially
      obscure. In this study, we report the application of a synthetic chloride (Cl(-))
      channel as a powerful tool to perturb and regulate a series of biological
      processes related or coupled to the changes of cell membrane potentials. This is
      the first example in which an artificial ion channel can regulate natural voltage
      gated calcium channels, intracellular calcium concentrations, and the contraction
      of smooth muscle cells via modulating cell membrane potentials in living cells
      and tissues. The present study on the ability of the synthetic chloride channel
      to perturb functions of natural ion channels may open new perspectives for the
      applications of other synthetic ion channels in biological systems.

PMID- 19772363
TI  - Ionic-type reactivity of 1,3-dibora-2,4-diphosphoniocyclobutane-1,3-diyls: regio-
      and stereoselective addition of hydracids.
AB  - Hydrogen chloride and trifluoromethane sulfonic acid readily add to the
      symmetrically substituted 1,3-dibora-2,4-diphosphoniocyclobutane-1,3-diyl (1) and
      unsymmetrically substituted 1,3-dibora-2,4-diphosphoniobicyclo[1.1.0]butane (3)
      under mild conditions, substantiating some formal analogies between the PBPB
      diradicaloids D and alkenes. X-ray diffraction analyses carried out on all the
      resulting 1,3-diborata-2,4-diphosphoniocyclobutanes (2, 4-6) revealed that the
      reactions proceed with complete stereo- and regio-selectivity, and that an
      unusual t-Bu --> i-Bu isomerization can occur at boron. DFT calculations shed
      more light on the factors controlling the regioselectivity of the additions, its
      concerted versus stepwise character, and support an original two-step mechanism
      for the t-Bu --> i-Bu isomerization, involving a carbocationic sigma-borane
      adduct as a key intermediate.

PMID- 19772364
TI  - Atmospheric heterogeneous stereochemistry.
AB  - While many biogenic and anthropogenic organic constituents in the atmosphere are
      surface-active and chiral, the role of stereochemistry in heterogeneous oxidation
      chemistry in the atmosphere has not yet been evaluated. Here, we present
      nonlinear vibrational surface spectra of fused silica substrates functionalized
      with quinuclidine diastereomers during exposure to 10(11) to 10(13) molecules of
      ozone per cm(3) in 1 atm helium to model ozone-limited and ozone-rich
      tropospheric conditions. Kinetic studies show that diastereomers that orient
      their reactive C=C double bonds toward the gas phase exhibit heterogeneous
      ozonolysis rate constants that are 2 times faster than diastereomers that orient
      their C=C double bonds away from the gas phase. Insofar as our laboratory model
      studies are representative of real world environments, our studies suggest that
      the propensity of aerosol particles coated with chiral semivolatile organic
      compounds to react with ozone may depend on stereochemistry. We expect that the
      differences in chemical accessibility will lead to the enrichment of one
      oxidation product stereoisomer over the other. The oxidation products could be
      gaseous or surface-bound, indicating that kinetic resolution could lead to the
      stereochemical enrichment of the gas phase or the aerosol, which may have also
      been important in prebiotic chemistry. Implications of these results for chiral
      markers that would allow for source appointments of anthropogenic versus biogenic
      carbon emissions are discussed.

PMID- 19772365
TI  - Neighboring amide participation in thioether oxidation: relevance to biological
      oxidation.
AB  - To investigate neighboring amide participation in thioether oxidation, which may
      be relevant to brain oxidative stress accompanying beta-amyloid peptide
      aggregation, conformationally constrained methylthionorbornyl derivatives with
      amido moieties were synthesized and characterized, including an X-ray
      crystallographic study of one of them. Electrochemical oxidation of these
      compounds, studied by cyclic voltammetry, revealed that their oxidation peak
      potentials were less positive for those compounds in which neighboring group
      participation was geometrically possible. Pulse radiolysis studies provided
      evidence for bond formation between the amide moiety and sulfur on one-electron
      oxidation in cases where the moieties are juxtaposed. Furthermore, molecular
      constraints in spiro analogues revealed that S-O bonds are formed on one-electron
      oxidation. DFT calculations suggest that isomeric sigma*(SO) radicals are formed
      in these systems.

PMID- 19772366
TI  - Anatomy of one-dimensional cocrystals: randomness into order.
AB  - A 2D cocrystal that displays random mixing along one axis and periodic ordering
      along the other axis is discovered. The characteristics and formation process of
      this "1D-cocrystal" are examined with atomic detail by scanning tunneling
      microscopy (STM) at the liquid/solid interface and through computed models. This
      type of cocrystallization causes an alignment shift to satisfy close packing. The
      frequency of the alignment shift can be controlled by variation of the ratio of
      adsorbates in solution. Furthermore, a reversible monolayer reorganization
      induced through perturbing the STM bias voltage provides not only mechanistic
      insights into the formation process of the 1D-cocrystal but also the potential
      for applications as a molecular switch. The control over surface composition and
      periodicity by controlling the molar ratio of components offers an unexploited
      approach to nanoscale patterning.

PMID- 19772367
TI  - Modification of symmetrically substituted phthalocyanines using click chemistry:
      phthalocyanine nanostructures by nanoimprint lithography.
AB  - Phthalocyanines (Pcs) are commonly applied to advanced technologies such as
      optical limiting, photodynamic therapy (PDT), organic field-effect transistors
      (OFETs), and organic photovoltaic (OPV) devices, where they are used as the p
      type layer. An approach to Pc structural diversity and the incorporation of a
      functional group that allows fabrication of solvent resistant Pc nanostructures
      formed by using a newly developed nanoimprint by melt processing (NIMP)
      technique, a variant of standard nanoimprint lithography (NIL), is reported.
      Copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC), a click chemistry
      reaction, serves as an approach to structural diversity in Pc macrocycles. We
      have prepared octaalkynyl Pc 1b and have modified this Pc using the CuAAC
      reaction to yield four Pc derivatives 5a-5d with different peripheral
      substituents on the macrocycle. One of these derivatives, 5c, has photo-cross
      linkable cinnamate residues, and we have demonstrated the fabrication of robust
      cross-linked photopatterned and imprinted nanostructures from this material.

PMID- 19772369
TI  - The heart truth professional education campaign on women and heart disease: needs
      assessment and evaluation results.
AB  - BACKGROUND: Heart disease is the leading cause of death for women in the United
      States. Research has identified that women are less likely than men to receive
      medical interventions for the prevention and treatment of heart disease. METHODS
      AND RESULTS: As part of a campaign to educate healthcare professionals, 1245
      healthcare professionals in 11 states attended a structured 1-hour continuing
      medical education (CME) program based on the 2004 AHA Evidence-Based Guidelines
      for Cardiovascular Disease Prevention in Women and completed a pretest and
      posttest evaluation. We identified significant knowledge deficits in the pretest:
      45% of attendees would initially recommend lifestyle changes alone, rather than
      statin therapy, for women diagnosed with coronary artery disease (CAD); 38%
      identified statin therapy as less effective in women compared with men for
      preventing CAD events; 27% identified Asian American women at low risk (rather
      than high risk) for type 2 diabetes mellitus (DM); and 21% identified processed
      meat (rather than baked goods) as the principal dietary source of trans fatty
      acids. Overall, healthcare professionals answered 5.1 of 8 knowledge questions
      correctly in the pretest, improving to 6.8 questions in the posttest (p < 0.001).
      Family physicians, obstetrician/gynecologists, general internists, nurse
      practitioners/physician assistants, and registered nurses all statistically
      significantly improved knowledge and self-assessed skills and attitudes as
      measured by the posttest. CONCLUSIONS: Significant knowledge deficits are
      apparent in a cross-section of healthcare providers attending a CME lecture on
      women and heart disease. A 1-hour presentation was successful in improving
      knowledge and self-assessed skills and attitudes among primary care physicians,
      nurse practitioners, physician assistants, and registered nurses.

PMID- 19772370
TI  - Emerging drugs for acne.
AB  - Acne vulgaris is a common skin disorder that affects most individuals at some
      point in their lives. It may result in significant morbidity, including cutaneous
      scarring and psychological impairment. Current treatments include topical
      retinoids, benzoyl peroxide, topical and systemic antibiotics, and systemic
      isotretinoin. There are growing concerns of rising antibiotic resistance,
      significant side effects of isotretinoin therapy, and lack of safe and effective
      treatment for pregnant females. Recent advances in the pathogenesis of acne have
      led to a greater understanding of the underlying inflammatory mechanisms and the
      role the Propionibacterium acnes and biofilms. This has led to the development of
      new therapeutic targets. This article reviews emerging treatments of acne,
      including topical picolinic acid, topical antibiotic dapsone, systemic zinc
      salts, oral antibiotic lymecycline, new formulations of and synergistic
      combinations of benzoyl peroxide, photodynamic therapy with topical
      photosensitizers and potential acne vaccines.

PMID- 19772371
TI  - Emerging cognitive enhancing drugs.
AB  - BACKGROUND: Advances in health sciences during the last century have increased
      the average age in industrialized nations. Despite this progress,
      neurodegenerative diseases that affect higher order thinking and memory continue
      to increase in prevalence as they take a devastating toll on human productivity
      in the later years. There is an acute need for new drugs and therapeutic
      approaches for treating these severe diseases, and also for improving the quality
      of cognitive function associated with normal aging and in many other disorders
      and syndromes that present with cognitive dysfunction. OBJECTIVE: The purpose of
      this review is to ascertain the pharmacological approaches being exploited to
      improve cognition and memory and to determine the most relevant and effective
      directions taken for new drug discovery. Limitations and difficulties encountered
      in this effort also are discussed. METHODS: This review focuses primarily on
      compounds already undergoing clinical trials for improving cognition and memory
      with some discussion of rising new drug targets. RESULTS/CONCLUSION: Compounds
      that act on allosteric sites on neurotransmitter receptors are expected to lead
      the field with new levels of specificity and reduced side effects. New multi
      functional compounds can be designed that can both improve cognition and slow the
      process of disease.

PMID- 19772372
TI  - Emerging apoptosis agonists for bladder cancer.
AB  - Bladder cancer is a very common and aggressive tumor entity. Unfortunately,
      common chemotherapy is not able to cure advanced bladder cancer. Therefore,
      several attempts have been made to improve the response to chemotherapy. Because
      changes in apoptotic pathways are frequent events in the development of
      chemoresistance of malignancies, pro-apoptotic treatment seems promising for the
      improvement of bladder cancer prognosis. Preclinical data show potential ways for
      a successful combination of apoptosis agonists with conventional chemotherapy.
      None of these principles has so far successfully been translated into clinical
      trials for bladder cancer. This review describes actual studies and future
      perspectives for apoptotic agonists in bladder cancer.

PMID- 19772373
TI  - Cultural competence of healthcare professionals caring for breastfeeding mothers
      in urban areas.
AB  - OBJECTIVE: Breastfeeding is strongly influenced by cultural considerations.
      Therefore, culturally competent healthcare professionals can provide more
      appropriate breastfeeding support and information. The purpose of this study was
      to measure the general cultural competence of healthcare professionals caring for
      breastfeeding mothers in an urban area. METHODS: Healthcare professionals
      involved in the care of breastfeeding mothers in New York, NY were surveyed
      utilizing Campinha-Bacote's Inventory for Assessing the Process of Cultural
      Competence Among Healthcare Professionals-Revised (IAPCC-R) and a demographic
      data instrument. RESULTS: Of 141 surveyed healthcare professionals, 128 completed
      the questionnaire. There were 18 physicians, 69 nurses, and 41 other allied
      health professionals in this sample. Of those surveyed, 76% reported a majority
      of their clients' cultural background differed from their own, 56% had studied
      cultural diversity in school, and 68% had attended a continuing education class
      on the subject. The mean score on the IAPCC-R was 68 +/- 9, which is culturally
      aware on Campinha-Bacote's continuum of culturally incompetent, culturally aware,
      culturally competent, and culturally proficient. There was no statistical
      difference in IAPCC-R scores whether or not the respondents had attended courses
      in school or worked with a more diverse population. Professionals who had
      attended continuing education courses on cultural diversity had significantly
      higher total scores (69 +/- 9 vs. 65 +/- 7, P = 0.021) and scores for cultural
      skill (14 +/- 2 vs. 13 +/- 2, P = 0.002) and desire (17 +/- 2 vs. 16 +/- 2, P =
      0.011). Twenty-three percent of the participants achieved a score of cultural
      competence. They were more likely to have attended continuing education courses
      on cultural diversity (31% vs. 7%, P = 0.0003). CONCLUSIONS: The majority (77%)
      of healthcare professionals caring for breastfeeding mothers in urban areas did
      not achieve a score of cultural competence.

PMID- 19772374
TI  - Early exclusive breastfeeding and maternal attitudes towards infant feeding in a
      population of new mothers in San Francisco, California.
AB  - BACKGROUND: Positive parental attitudes towards infant feeding are an important
      component in child nutritional health. Previous studies have found that
      participants in the Special Supplemental Women, Infants, and Children (WIC)
      Program have lower breastfeeding rates and attitudes that do not contribute
      towards healthy infant feeding in spite of breastfeeding and nutrition education
      programs targeting WIC participants. The objective of this study was to assess
      the frequency of exclusive breastfeeding in the early postpartum period and
      maternal attitudes towards breastfeeding in a population of mothers at two San
      Francisco hospitals and in relation to WIC participation status. METHODS: We
      interviewed women who had recently delivered a healthy newborn using a structured
      interview. RESULTS: A high percentage (79.8%) of our sample was exclusively
      breastfeeding at 1-4 days postpartum. We did not find any significant differences
      in rates of formula or mixed feeding by WIC participant status. Independent risk
      factors for mixed or formula feeding at 1-3 days postpartum included
      Asian/Pacific Islander ethnicity (odds ratio [OR] 2.90, 95% confidence interval
      [CI] 1.17-7.19). Being a college graduate was associated with a decreased risk of
      formula/mixed feeding (OR 0.28, 95% CI 0.10-0.79). We also found that thinking
      breastfeeding was physically painful and uncomfortable was independently
      associated with not breastfeeding (OR 1.41, 95% CI 1.06-1.89). CONCLUSIONS:
      Future studies should be conducted with Asian-Americans and Pacific Islanders to
      better understand the lower rates of exclusive breastfeeding in this population
      and should address negative attitudes towards breastfeeding such as the idea that
      breastfeeding is painful or uncomfortable.

PMID- 19772375
TI  - Parathyroid hormone-related protein in preterm human milk.
AB  - BACKGROUND: Parathyroid hormone-related protein (PTHrP) has the ability to
      activate parathyroid hormone receptors and cause hypercalcemia. High
      concentrations of PTHrP are found in human breastmilk of mothers of term-infants.
      It is not known whether PTHrP is excreted in preterm human milk. This study
      tested the hypothesis that PTHrP concentrations in milk obtained from mothers of
      preterm infants are similar to those found in milk from mothers of term infants.
      METHODS: We collected samples of expressed human milk obtained from 27 mothers of
      preterm infants (27-34 weeks' gestation) and from 16 mothers of full-term
      infants. Samples were collected within the first 72 hours postpartum (colostrum)
      and again at 1 and 2 weeks postpartum. PTHrP concentrations in these samples were
      measured by two-site immunoradiometric assay. RESULTS: PTHrP concentrations were
      significantly higher in samples obtained after 1 week postpartum than in samples
      obtained during the first 72 hours of life in breastmilk obtained from mothers of
      both term and preterm infants (P < 0.0001). PTHrP concentrations were similar in
      colostrum and after 1 week in term and preterm milk. PTHrP concentrations after 2
      weeks of lactation were significantly higher in samples obtained from mothers of
      term infants (P < 0.006). CONCLUSION: Human milk expressed by mothers of preterm
      infants contains amounts of PTHrP similar to those measured in milk expressed by
      mothers of term infants.

PMID- 19772376
TI  - Use of xanthan and its binary blends with synthetic polymers to design controlled
      release formulations of buccoadhesive nystatin tablets.
AB  - Various buccoadhesive nystatin tablets formulations containing xanthan, carbopols
      (934P, 971P, 974P), PVP K30 or PEG 6000 or their binary blends were prepared. The
      powders were compressed into tablets at a constant compression pressure. Drug
      release behaviour, swelling and erosion indices and strength of bioadhesion in
      vitro to a biological membrane were investigated. The interaction between
      nystatin and polymers was investigated by DSC and FT-IR. Tablets containing the
      different types of carbopol alone consistently showed an initial burst release of
      drug, whereas this was not observed for matrices containing xanthan or xanthan
      carbopol. The presence of PEG in xanthan-containing formulations induced an
      increase in dissolution rate; however, in the absence of xanthan the amount of
      drug release from a PEG matrix was reduced to < 15% over 8 h dissolution. The
      presence of PVP increased the dissolution rate of nystatin due to the relative
      hydrophilicity of PVP. The presence of calcium ions induced a more rigid gel in
      the xanthan matrix as a result of interaction between the polymer and calcium
      ions. Xanthan can be used in potential mucoadhesive formulations containing
      nystatin to produce a controlled release of the drug and the outcomes of this
      work may provide a suitable strategy for matrix selection to provide more
      efficacious treatment alternatives for candidiasis and other disease processes
      for significant patient populations.

PMID- 19772377
TI  - Controlled release polymeric ocular delivery of acyclovir.
AB  - The aim of the present study was to formulate and evaluate controlled release
      polymeric ocular delivery of acyclovir. Reservoir-type ocular inserts were
      fabricated by sandwiching hydroxypropyl methylcellulose (HPMC) matrix film
      containing acyclovir between two rate controlling membranes of cellulose acetate
      phthalate (CAP). The solubility and dissolution rate of poorly soluble acyclovir
      was enhanced by preparing binary systems with beta-cyclodextrin and then
      incorporated into HPMC matrix. Nine formulations (AB-1 to AB-9) with varying
      ratio of HPMC (drug matrix) and CAP (rate controlling membrane) were developed
      and sterilized by gamma radiation. The formulations were subjected to various
      physico-chemical evaluations. The in vitro release profile of all the
      formulations showed a steady, controlled drug release up to 20 h with non-Fickian
      diffusion behavior. A high correlation coefficient found between in vitro/in vivo
      release rate studies. Formation of acyclovir complex was confirmed by
      differential scanning calorimetry. In addition, dissolution rate studies revealed
      improved solubility of acyclovir when complexed with beta-cyclodextrin. Stability
      studies showed that the ocular inserts could be stored safely at study storage
      conditions. In conclusion, the present study demonstrated controlled release
      formulation of acyclovir inserts for ocular delivery using biodegradable
      polymers.

PMID- 19772378
TI  - Effects of antenatal corticosteroids on urinary markers of the initiation of
      lactation in pregnant women.
AB  - BACKGROUND: Antenatal corticosteroids are given to most women at risk of preterm
      delivery, although many do not eventually deliver preterm. Profound disruptions
      of lactation have been shown in ewes after antenatal corticosteroid treatment,
      but little is known of the effect on lactation in women. This study aimed to
      investigate the effects of antenatal corticosteroid treatment on mammary
      secretion during pregnancy in women. METHODS: We conducted a prospective cohort
      study of women receiving betamethasone for anticipated preterm delivery (n = 87).
      Women collected 24-hour urine samples on days 1, 2, 3, 5, 7, and 14 after
      treatment if they remained pregnant. We measured urinary excretion of
      pregnanediol glucuronide (PdG), a major metabolite of progesterone and lactose,
      which indicates mammary secretion during pregnancy. Withdrawal of progesterone
      triggers the onset of mammary secretion. RESULTS: Median (range) gestational age
      at treatment was 28.8 (23.6-33.6) weeks. A total of 330 24-hour urine samples
      were collected. Median (range) excretion of PdG was 1.355 (0.139-5.069) mmol/24
      hours, and lactose excretion was 0.823 (0.035-6.676) mmol/24 hours. Both PdG and
      lactose excretion increased with increasing gestational age (P < 0.001). After
      adjustment for gestational age, there were significant transient increases in
      lactose excretion (P < 0.001) after betamethasone treatment but no changes in PdG
      excretion (P = 0.435). CONCLUSIONS: Antenatal betamethasone treatment was
      associated with a transient premature secretory activation while women were still
      pregnant.

PMID- 19772379
TI  - Layer-by-Layer modification of poly (methyl methacrylate) intra ocular lens: drug
      delivery applications.
AB  - Even though infection followed by Intra ocular lens (IOL) implantation is a rare
      complication, therapeutic options are limited and it affects the vision
      seriously. Interestingly, IOL itself acts as substrate for the adhesion and
      proliferation of bacteria. An approach to facilitate antibacterial drug
      adsorption onto the surface of IOL through the modification of IOL surface using
      the concept of Layer-by-Layer (LbL) formation without sacrificing the vital
      optical features of the IOLs is presented here. Polyelectroylte multilayers
      incorporating ampicillin was fabricated on the IOLs using LbL deposition of Poly
      (sodium 4-styrenesulfonate) (PSS) and Poly (ethylenimine) (PEI). Altogether six
      layers were formed. The layer formation enabled the IOL to adsorb the drug and
      modulated the release in a sustained fashion. It appears that using this
      strategy, IOLs could be modified using a variety of degradable or non-degradable
      materials to precisely control the delivery of active components to protect eye
      and the device.

PMID- 19772380
TI  - Design and evaluation of thermoreversible in situ gelling system of forskolin for
      the treatment of glaucoma.
AB  - The contact time of a vehicle on the cornea is of utmost importance for
      ophthalmic drug delivery. The poor bioavailability and therefore poor therapeutic
      response exhibited by the conventional ophthalmic solutions due to pre-corneal
      elimination of a drug may be overcome by the use of the in situ gel forming
      systems, which upon instillation as drops into the eye, undergo a sol-gel
      transition in the cul-de-sac. The purpose of this work was to develop an
      ophthalmic delivery system of the forskolin, based on the concept of temperature
      activated in situ gelation. Poloxamer 407 (Pluronic F-127) is a block copolymer
      made of poly (oxy ethylene) and poly (oxy propylene). The sol-gel transition is
      induced by an increase in temperature; however, it depends on the concentration
      of the polymer and presence of other additives. The developed formulations were
      therapeutically efficacious (on albino New Zealand rabbit model); reducing intra
      ocular pressure (IOP) for 12 hours and showed sol-gel phase transition (gelling)
      temperature of 22 degrees C and sustained drug release 72% +/- 0.056% in vitro
      behavior over a period of 4 h.

PMID- 19772381
TI  - In vivo effects on the expression of vascular endothelial growth factor-A165
      messenger ribonucleic acid of an infrared diode laser associated or not with a
      visible red diode laser.
AB  - OBJECTIVE: This study investigated and correlated the kinetic expression of
      vascular endothelial growth factor (VEGF)-A(165) messenger ribonucleic acid
      (mRNA) with the associated use or not of an infrared laser and a visible red
      laser during the wound healing in rats. BACKGROUND DATA: There is a lack of
      scientific evidence demonstrating the influence of low-level laser therapy (LLLT)
      on the expression of VEGF mRNA in vivo. MATERIALS AND METHODS: Forty-five Wistar
      rats were randomly allocated to one of three groups: I (n = 5, nonoperated
      animals), II (n = 25, operated animals), and III (n = 25, animals operated and
      subjected to laser irradiation). A surgical wound was performed using a scalpel
      in the right side of the tongue of operated animals. In group III, two sessions
      of laser irradiation were performed, one right after the surgical procedure
      (infrared laser, 780 nm, 70 mW, 35 J/cm(2)) and the other 48 h later (visible red
      laser, 660 nm, 40 mW, 5 J/cm(2)). Five animals each were sacrificed 1, 3, 5, and
      7 days postoperatively in groups II and III, and samples of tongue tissue were
      obtained. The animals of group I were sacrificed on day 7. Total RNA was
      extracted using guanidine-isothiocyanate-phenol-chloroform method. The results of
      horizontal electrophoresis after reverse transcription polymerase chain reaction
      permitted the ratio of VEGF-A(165) mRNA and glyceraldehyde 3-phosphate
      dehydrogenase mRNA expression for groups I, II, and III to be assessed (two-way
      analysis of variance and Tukey test, p < 0.05). RESULTS: The expression of VEGF
      A(165) mRNA in group II (0.770 +/- 0.098) was statistically greater than that
      observed in groups I (0.523 +/- 0.164) and III (0.504 +/- 0.069) in the first day
      after surgery (p < 0.05). Significant differences between the groups were not
      observed in other time periods. CONCLUSION: LLLT influenced the expression of
      VEGF-A(165) mRNA during wound healing after a surgical procedure on the tongue of
      Wistar rats.

PMID- 19772382
TI  - Comparative evaluation of the powder and compression properties of various grades
      and brands of microcrystalline cellulose by multivariate methods.
AB  - The present work challenges a newly developed approach to tablet formulation
      development by using chemically identical materials (grades and brands of
      microcrystalline cellulose). Tablet properties with respect to process and
      formulation parameters (e.g. compression speed, added lubricant and Emcompress
      fractions) were evaluated by 2(3)-factorial designs. Tablets of constant true
      volume were prepared on a compaction simulator at constant pressure (approx. 100
      MPa). The highly repeatable and accurate force-displacement data obtained was
      evaluated by simple 'in-die' Heckel method and work descriptors. Relationships
      and interactions between formulation, process and tablet parameters were
      identified and quantified by multivariate analysis techniques; principal
      component analysis (PCA) and partial least square regressions (PLS). The method
      proved to be able to distinguish between different grades of MCC and even between
      two different brands of the same grade (Avicel PH 101 and Vivapur 101). One
      example of interaction was studied in more detail by mixed level design: The
      interaction effect of lubricant and Emcompress on elastic recovery of Avicel PH
      102 was demonstrated to be complex and non-linear using the development tool
      under investigation.

PMID- 19772384
TI  - On the parameterized complexity of pooling design.
AB  - Pooling design is a very helpful tool for reducing the number of tests in DNA
      library screening, which is a key process to obtain high-quality DNA libraries
      for studying gene functions. Three basic problems in pooling design are, given an
      m x n binary matrix and a positive integer d, to decide whether the matrix is d
      separable (d-separable, or d-disjunct). The three problems are all known to be
      coNP-complete. Since in most applications, d is a small integer compared to n, it
      is interesting to investigate whether there are efficient algorithms solving the
      above problems when the value of d is small. In this article, we give a negative
      answer to the above question by studying the parameterized complexity of these
      three problems, with d as the parameter. We show that the parameterized versions
      of all the three problems are co-W[2]-complete. An immediate implication of our
      results is that, given an m x n binary matrix and a positive integer d, a
      deterministic algorithm with running time f(d) x (mn)(O(1)) (where f is an
      arbitrary computable function) to decide whether the matrix is d-separable (d
      separable, or d-disjunct) should not be expected.

PMID- 19772383
TI  - BCL::contact-low confidence fold recognition hits boost protein contact
      prediction and de novo structure determination.
AB  - Knowledge of all residue-residue contacts within a protein allows determination
      of the protein fold. Accurate prediction of even a subset of long-range contacts
      (contacts between amino acids far apart in sequence) can be instrumental for
      determining tertiary structure. Here we present BCL::Contact, a novel contact
      prediction method that utilizes artificial neural networks (ANNs) and specializes
      in the prediction of medium to long-range contacts. BCL::Contact comes in two
      modes: sequence-based and structure-based. The sequence-based mode uses only
      sequence information and has individual ANNs specialized for helix-helix, helix
      strand, strand-helix, strand-strand, and sheet-sheet contacts. The structure
      based mode combines results from 32-fold recognition methods with sequence
      information to a consensus prediction. The two methods were presented in the
      6(th) and 7(th) Critical Assessment of Techniques for Protein Structure
      Prediction (CASP) experiments. The present work focuses on elucidating the impact
      of fold recognition results onto contact prediction via a direct comparison of
      both methods on a joined benchmark set of proteins. The sequence-based mode
      predicted contacts with 42% accuracy (7% false positive rate), while the
      structure-based mode achieved 45% accuracy (2% false positive rate). Predictions
      by both modes of BCL::Contact were supplied as input to the protein tertiary
      structure prediction program Rosetta for a benchmark of 17 proteins with no close
      sequence homologs in the protein data bank (PDB). Rosetta created higher accuracy
      models, signified by an improvement of 1.3 A on average root mean square
      deviation (RMSD), when driven by the predicted contacts. Further, filtering
      Rosetta models by agreement with the predicted contacts enriches for native-like
      fold topologies.

PMID- 19772385
TI  - Parallel GPU implementation of iterative PCA algorithms.
AB  - Principal component analysis (PCA) is a key statistical technique for
      multivariate data analysis. For large data sets, the common approach to PCA
      computation is based on the standard NIPALS-PCA algorithm, which unfortunately
      suffers from loss of orthogonality, and therefore its applicability is usually
      limited to the estimation of the first few components. Here we present an
      algorithm based on Gram-Schmidt orthogonalization (called GS-PCA), which
      eliminates this shortcoming of NIPALS-PCA. Also, we discuss the GPU (Graphics
      Processing Unit) parallel implementation of both NIPALS-PCA and GS-PCA
      algorithms. The numerical results show that the GPU parallel optimized versions,
      based on CUBLAS (NVIDIA), are substantially faster (up to 12 times) than the CPU
      optimized versions based on CBLAS (GNU Scientific Library).

PMID- 19772387
TI  - Natural history of compensated hepatitis C virus-related cirrhosis in HIV
      infected patients.
AB  - OBJECTIVE: To provide information about the incidence and predictors of liver
      decompensation and death due to liver failure in human immunodeficiency virus
      (HIV)-infected patients with compensated hepatitis C virus (HCV)-related
      cirrhosis. METHODS: Prospective cohort study of 154 HIV-HCV-coinfected patients
      with a new diagnosis of Child-Pugh-Turcotte (CPT) class A compensated cirrhosis.
      We evaluated time from diagnosis to the first liver decompensation and death from
      liver disease, as well as predictors of these outcomes. RESULTS: Thirty-six
      patients (23.4%) developed liver decompensation. The incidence of liver
      decompensation was 6.40 cases per 100 person-years (95% confidence interval [CI],
      4.18-9.38 cases per 100 person-years). Factors independently associated with
      liver decompensation were lack of HCV therapy (hazard ratio [HR], 3.38; 95% CI,
      1.09-10.53; P = .035), baseline CD4 cell counts <or=300 cells/mm3 (HR, 2.12; 95%
      CI, 1.14-5.04; P = .021), CPT score 6 versus 5 (HR, 3.33; 95% CI, 1.39-7.69; P =
      .007), and a diagnosis of cirrhosis based on data other than biopsy or transient
      elastography (HR, 2.09; 95% CI, 1.05-4.16; P = .036 ). Fifteen patients (9.7%)
      died; 11 (73%) of these 15 died from liver disease (mortality due to liver
      failure, 2.44 deaths per 100 person-years; 95% CI, 1.21-4.36 deaths per 100
      person-years). Hepatic encephalopathy as the first liver decompensation (HR,
      20.67; 95% CI, 2.71-157.57; P = .003), baseline CD4 count <or=300/mm3 (HR, 0.24;
      95% CI, 0.07-0.78; P = 0.17), and baseline CPT score 6 (HR, 4.50; 95% CI, 1.63
      12.37; P = .004) were independently associated with liver-related death.
      CONCLUSIONS: The incidence of clinical liver events in HIV-HCV-coinfected
      patients with CPT class A compensated cirrhosis is close to that previously
      reported in HCV-monoinfected patients. Lower baseline CD4 cell counts, lack of
      therapy against HCV, and higher CPT score are the factors related to the
      occurrence of clinical liver events. Minimal changes in CPT score have strong
      impact in the prognosis of this population.

PMID- 19772386
TI  - Impact of hepatitis B virus infection on human immunodeficiency virus response to
      antiretroviral therapy in Nigeria.
AB  - BACKGROUND: As highly active antiretroviral therapy (ART) is introduced into
      areas of the world in which hepatitis B virus (HBV) infection is highly endemic,
      it is important to determine the influence of HBV on persons with human
      immunodeficiency virus (HIV) and HBV coinfection who are receiving ART. METHODS:
      We studied 1564 HIV-infected patients in Jos, Nigeria, who initiated ART.
      Participants with HIV-HBV coinfection had hepatitis B e antigen (HBeAg) and HBV
      DNA status determined. CD4+ T cell count and HIV load at ART initiation were
      compared between individuals with HIV monoinfection and those with HIV-HBV
      coinfection with use of univariate methods. Regression analyses were used to
      determine if HBeAg status or HBV DNA at ART initiation were associated with
      baseline HIV parameters or ART response. RESULTS: The median CD4+ T cell count of
      the 262 participants with HIV-HBV coinfection (16.7%) was 107 cells/mL, compared
      with 130 cells/mL for participants with HIV monoinfection at ART initiation (P =
      .001). Participants with HIV-HBV coinfection also had higher HIV loads than did
      patients with HIV monoinfection (4.96 vs 4.75 log10 copies/mL; p = .02 ). Higher
      HBV DNA and detectable HBeAg levels were independently associated with lower CD4+
      T cell counts at ART initiation but not with higher HIV loads. In a multivariable
      model, HBeAg-positive patients were less likely than HBeAg-negative patients to
      suppress HIV replication to <or= 400 copies/mL (odds ratio, 0.54; P = .03 ) at 24
      weeks, but they had similar CD4+ T cell increases. At 48 weeks, there was no
      significant effect of HBeAg status on ART response. CONCLUSIONS: Among HIV
      infected Nigerian individuals, HBV coinfection, especially among those with high
      levels of HBV replication, was associated with lower CD4+ T cell counts at ART
      initiation, independent of HIV RNA level. Patients with HBeAg-positive status had
      a slower virological response to ART, compared with HBeAg-negative patients.
      Further work is needed to understand the effects of HBV on CD4+ T cells.

PMID- 19772388
TI  - Efficacy and safety of pegylated interferon plus ribavirin in HIV and hepatitis C
      virus-coinfected patients with advanced immunosuppression.
AB  - BACKGROUND: The aim of this study was to assess the efficacy and safety of
      pegylated interferon (IFN) plus ribavirin (RBV) in human immunodeficiency virus
      (HIV) and hepatitis C virus (HCV)-coinfected patients with severe
      immunodeficiency in a clinical cohort. BACKGROUND. A total of 542 HIV-infected
      patients receiving treatment with pegylated IFN plus RBV from June 2001 through
      April 2007 were included in this study. The outcome variables were sustained
      virologic response (SVR) rate and the emergence of AIDS-defining events during
      HCV infection therapy. SVR rates among patients with a CD4 cell count <or=250
      cells/mm(3) at baseline were compared with those among patients with CD4 cell
      counts >250 cells/mm(3). The association between SVR and potential predictors was
      analyzed. RESULTS: Ten (26%) of 39 individuals with a baseline CD4 cell count 250
      cells/mm(3) and 198 (39%) of 503 with baseline CD4 cell counts >or=250 CD4
      cells/mm(3) achieved SVR (P = .09). In a nested case-control study with
      populations matched at a 1:2 ratio, the SVR rate was 26% in the CD4 cell count
      250 cells/mm(3) group and 32% in the CD4 cell count >250 cells/mm(3) group (P =
      .5). Baseline CD4 cell count (250 cells/mm(3) vs >250 cells/mm(3)) was not
      associated with SVR in the multivariate analysis. Two (5%) individuals in the CD4
      cell count 250 cells/mm(3) group experienced opportunistic events during follow
      up. In the CD4 cell count 250 cells/mm(3) group, severe hematological toxicity
      and pegylated IFN or RBV dosage reductions occurred in 16 (41%) and 12 (31%)
      patients, respectively. In the CD4 cell count >250 cells/mm(3) group, severe
      hematological toxicity and pegylated IFN or RBV dosage reductions occurred in 29%
      (P = .1) and 20% (P = .1) of patients, respectively. CONCLUSIONS: The efficacy of
      pegylated IFN plus RBV in HIV-HCV-coinfected patients with advanced
      immunosuppression is substantial and not significantly different to that observed
      in the overall coinfected population. HCV therapy is generally safe in the
      population of coinfected patients with advanced immunosuppression.

PMID- 19772389
TI  - Human health consequences of use of antimicrobial agents in aquaculture.
AB  - Intensive use of antimicrobial agents in aquaculture provides a selective
      pressure creating reservoirs of drug-resistant bacteria and transferable
      resistance genes in fish pathogens and other bacteria in the aquatic environment.
      From these reservoirs, resistance genes may disseminate by horizontal gene
      transfer and reach human pathogens, or drug-resistant pathogens from the aquatic
      environment may reach humans directly. Horizontal gene transfer may occur in the
      aquaculture environment, in the food chain, or in the human intestinal tract.
      Among the antimicrobial agents commonly used in aquaculture, several are
      classified by the World Health Organisation as critically important for use in
      humans. Occurrence of resistance to these antimicrobial agents in human pathogens
      severely limits the therapeutic options in human infections. Considering the
      rapid growth and importance of aquaculture industry in many regions of the world
      and the widespread, intensive, and often unregulated use of antimicrobial agents
      in this area of animal production, efforts are needed to prevent development and
      spread of antimicrobial resistance in aquaculture to reduce the risk to human
      health.

PMID- 19772390
TI  - Prophylaxis and treatment of invasive fungal diseases in allogeneic stem cell
      transplantation: results of a consensus process by Gruppo Italiano Trapianto di
      Midollo Osseo (GITMO).
AB  - In recent years, prospective studies have been conducted to assess the role of
      prophylaxis and treatment of invasive fungal diseases (IFD) in allogeneic
      hematopoietic stem cell transplantation (allo-HSCT). Although results of these
      studies have been encouraging, they have been unable to generate a consensus for
      optimal prophylaxis and treatment of IFD in the complex scenario of allo-HSCT. A
      consensus process was undertaken to describe and evaluate current information and
      practice regarding key questions on IFD management in allo-HSCT recipients; these
      questions were selected according to the criterion of relevance by group
      discussion. The Panel produced recommendations for risk stratification,
      prophylaxis, monitoring, and therapy of IFD and identified top priority issues
      for further investigation. The definition of the level of risk for IFD associated
      with the various types and phases of transplantation and the implementation of
      surveillance and diagnostic strategies are the critical determinants of the
      antifungal prophylactic and therapeutic approach for allo-HSCT recipients.

PMID- 19772392
TI  - Effect of lubricant on spreading of coating liquid on surface of tablets
      containing pancreatin.
AB  - The objective of this study was to evaluate the spreading of the coating liquid
      on different tablets containing pancreatin and microcrystalline cellulose. The
      effects of the ratio of the components, the presence of magnesium stearate and
      the blending circumstances were investigated. The contact angle of the liquids on
      the different tablets did not change linearly. For the mixture containing 50%
      pancreatin, the deviation of the measured value from the predicted one was more
      than 25%. This deterioration was also detected for mixtures containing 1%
      lubricant, but the extent was lower and was not modified by change of the mixing
      circumstances. This phenomenon was explained by the special microstructure of the
      surface of the tablet. This was predicted from the spreading coefficient,
      calculated from the surface free energy. The enrichment of pancreatin on the
      surface was preferred in binary mixtures. The spreading of magnesium stearate was
      most preferred for the powder mixture, and thus prediction of the properties of
      the tablet was easier for these mixtures. The extent of the effect of this
      excipient on the surface properties was very wide-ranging. The change in the
      spreading of the coating liquid was significant; however, the change in the work
      of friction was negligible.

PMID- 19772393
TI  - Human cytomegalovirus-encoded chemokine receptor homolog US28 stimulates the
      major immediate early gene promoter/enhancer via the induction of CREB.
AB  - The major immediate early (MIE) gene of cytomegalovirus plays a key role in
      determining the activation and replication of cytomegalovirus, which represents
      the most important event signaling the onset of virus-induced disease relapse.
      The viral-encoded chemokine receptor homolog US28 can constitutively activate
      many cellular transcription factors, which can bind to the promoter/enhancer of
      the MIE gene and activate its transcription. Using reporter gene assays in HEK293
      cells, we found that US28 enhanced the transcription efficiency of MIE and other
      genes via cAMP response element-binding protein (CREB). Inhibition of CREB
      partially blocked the effect of US28, whereas forskolin enhanced this effect.
      There was a direct correlation between CREB and transcription of MIE gene. These
      data, together with the broad-spectrum effect of cellular transcription factors,
      suggest that US28 may be involved in the very early transcription of the host
      cell during virus activation.

PMID- 19772394
TI  - Transdermal and intradermal iontophoretic delivery of dexamethasone sodium
      phosphate: quantification of the drug localized in skin.
AB  - In this study, the effect of iontophoresis on the transdermal and intradermal
      delivery of dexamethasone sodium phosphate (DEX-P) was examined in vitro and in
      vivo in the hairless rat model by skin permeation studies, tape stripping, and
      skin extraction. Cathodal or anodal iontophoresis (ITP) was performed and samples
      were analyzed by HPLC. In vitro experiments revealed that cathodal ITP
      significantly enhanced the cumulative amount of DEX-P permeating through the skin
      when compared to passive and anodal delivery. Tape stripping and skin extraction
      studies performed in vivo after ITP showed enhanced deposition of the drug in the
      stratum corneum and underlying skin when compared to passive delivery. The DEX-P
      and DEX depot formed in the stratum corneum and underlying skin were retained for
      at least 48 h and 24 h, respectively. In conclusion, ITP demonstrated potential
      as a feasible enhancement technique to drive the drug into and through the skin
      in significant amounts as compared to passive delivery.

PMID- 19772395
TI  - Transdermal delivery of a approximately 13 kDa protein--an in vivo comparison of
      physical enhancement methods.
AB  - The availability of several enhancement techniques has made it possible to study
      delivery of macromolecules through skin. This study was conducted to evaluate the
      transdermal delivery of a ~13 kDa protein using iontophoresis, sonophoresis, and
      microneedles alone or in combination. In vivo delivery experiments were carried
      out using hairless rats with daniplestim (DP) as the model protein (molecular
      weight: 12.760 kDa; isoelectric point, 6.2). Delivery enhancement abilities of
      the above techniques were evaluated at two different drug concentrations in the
      patch: 2 mg/mL and 5 mg/mL. At a drug loading concentration of 2 mg/mL maximum
      delivery was seen with the combination of microneedles and iontophoresis. At 5
      mg/mL, sonophoresis alone gave a C(max) of 8.22 +/- 5.9 ng/mL and a combination
      of sonophoresis and iontophoresis gave a C(max) of 4.9 +/- 1.8 ng/mL. The results
      of this study suggest that combination of microneedles and iontophoresis was the
      most effective approach in delivering a 13 kDa protein through the skin.

PMID- 19772397
TI  - Survival prediction and gene identification with penalized global AUC
      maximization.
AB  - Identifying genes (biomarkers) and predicting the clinical outcomes with censored
      survival times are important for cancer prognosis and pathogenesis. In this
      article, we propose a novel method with L(1) penalized global AUC summary
      maximization (L(1)GAUCS). The L(1)GAUCS method is developed for simultaneous gene
      (feature) selection and survival prediction. L(1) penalty shrinks coefficients
      and produces some coefficients that are exactly zero, and therefore selects a
      small subset of genes (features). It is a well-known fact that many genes are
      highly correlated in gene expression data and the highly correlated genes may
      function together. We, therefore, define a correlation measure to identify those
      genes such that their expression level may be low but they are highly correlated
      with the downstream highly expressed genes selected with L(1)GAUCS. Partial
      pathways associated with the correlated genes are identified with DAVID
      (http://david.abcc.ncifcrf.gov/). Experimental results with chemotherapy and gene
      expression data demonstrate that the proposed procedures can be used for
      identifying important genes and pathways that are related to time to death due to
      cancer and for building a parsimonious model for predicting the survival of
      future patients. Software is available upon request from the first author.

PMID- 19772398
TI  - Computation of rank and select functions on hierarchical binary string and its
      application to genome mapping problems for short-read DNA sequences.
AB  - Abstract We have developed efficient in-practice algorithms for computing rank
      and select functions on a binary string, based on a novel data structure, a
      hierarchical binary string with hierarchical accumulatives. It efficiently stores
      decomposed information on partial summations over various scales of subregions of
      a given binary string, so that the required space overhead ratio is only about
      3.5% irrespective of the string length. Values of rank and select functions are
      computed hierarchically in [(log(2)n)/8] iterations, where n is the string
      length. For example, for an unbiased random binary string of 64 G bits, each
      value of these functions can be computed in about a microsecond, on average, on a
      single 3.0-GHz CPU using 8+ GB of memory. We also present their applications to
      genome mapping problems for large-scale short-read DNA sequence data, especially
      produced by ultra-high-throughput new-generation DNA sequencers. The algorithms
      are applied to the binarization of the Burrows-Wheeler transform of the human
      genome DNA sequence. For the sake of high-speed performance, we adopted a
      somewhat stringent mapping condition that allows at most a single-base mismatch
      (either a substitution, insertion, or deletion of a single base) per query
      sequence. An experimentally implemented program mapped several thousands of
      sequences per second on a single 3.0-GHz CPU, several times faster than ELAND, a
      widely used mapping program with the Illumina-Solexa 1G analyser.

PMID- 19772399
TI  - Esophageal diverticulum presenting as a thyroid nodule and diagnosed on fine
      needle aspiration.

PMID- 19772400
TI  - Severe ophthalmopathy developing after treatment of coexisting malignant struma
      ovarii and Graves' disease.

PMID- 19772401
TI  - Minimally invasive decompression of a suboccipital osseous prominence causing
      rotational vertebral artery occlusion. Case report.
AB  - Surgical decompression of the vertebral artery (VA) between the suboccipital area
      and C-1 is typically performed via a large midline incision or a far-lateral
      approach. Such traditional open approaches are often associated with significant
      muscle dissection and blood loss. In this case, a 12-year-old boy suffered a
      stroke related to a VA rotational occlusion (bow hunter syndrome) and dissection
      due to a prominent suboccipital bone mass. Successful decompression of the VA was
      performed via a minimally invasive 22-mm tubular retractor. This is the first
      reported case report of a minimally invasive decompression of the VA between the
      skull base and C-1.

PMID- 19772402
TI  - Atlantal fracture with transverse ligament disruption in a child. Case report.
AB  - Even though fractures in children with immature spines occur predominantly in the
      upper cervical spine, isolated C-1 fractures are relatively rare. The fractures
      in almost all cases reported to date were considered stable due to the presence
      of the intact transverse ligament. The authors report the case of a young child
      who sustained a Jefferson fracture and in whom MR imaging revealed disruption of
      the transverse ligament. Although surgical treatment has been suggested as the
      treatment of choice for children with unstable atlantoaxial injuries, external
      immobilization alone allowed a full recovery in the patient with no evidence of
      instability at follow-up.

PMID- 19772403
TI  - Neurosurgical management of intractable rolandic epilepsy in children: role of
      resection in eloquent cortex. Clinical article.
AB  - OBJECT: The authors undertook this study to review their experience with cortical
      resections in the rolandic region in children with intractable epilepsy. METHODS:
      The authors retrospectively reviewed the medical records obtained in 22 children
      with intractable epilepsy arising from the rolandic region. All patients
      underwent preoperative electroencephalography (EEG), MR imaging, prolonged video
      EEG recordings, functional MR imaging, magnetoencephalography, and in some
      instances PET/SPECT studies. In 21 patients invasive subdural grid and depth
      electrode monitoring was performed. Resection of the epileptogenic zones in the
      rolandic region was undertaken in all cases. Seizure outcome was graded according
      to the Engel classification. Functional outcome was determined using validated
      outcome scores. RESULTS: There were 10 girls and 12 boys, whose mean age at
      seizure onset was 3.2 years. The mean age at surgery was 10 years. Seizure
      duration prior to surgery was a mean of 7.4 years. Nine patients had preoperative
      hemiparesis. Neuropsychological testing revealed impairment in some domains in 19
      patients in whom evaluation was possible. Magnetic resonance imaging
      abnormalities were identified in 19 patients. Magnetoencephalography was
      performed in all patients and showed perirolandic spike clusters on the affected
      side in 20 patients. The mean duration of invasive monitoring was 4.2 days. The
      mean number of seizures during the period of invasive monitoring was 17. All
      patients underwent resection that involved primary motor and/or sensory cortex.
      The most common pathological entity encountered was cortical dysplasia, in 13
      children. Immediately postoperatively, 20 patients had differing degrees of
      hemiparesis, from mild to severe. The hemiparesis improved in all affected
      patients by 3-6 months postoperatively. With a mean follow-up of 4.1 years
      (minimum 2 years), seizure outcome in 14 children (64%) was Engel Class I and
      seizure outcome in 4 (18%) was Engel Class II. In this series, seizure outcome
      following perirolandic resection was intimately related to the child's age at the
      time of surgery. By univariate logistic regression analysis, age at surgery was a
      statistically significant factor predicting seizure outcome (p < 0.024).
      CONCLUSIONS: Resection of rolandic cortex for intractable epilepsy is possible
      with expected morbidity. Accurate mapping of regions of functional cortex and
      epileptogenic zones may lead to improved seizure outcome in children with
      intractable rolandic epilepsy. It is important to counsel patients and families
      preoperatively to prepare them for possible worsened functional outcome involving
      motor, sensory and/or language pathways.

PMID- 19772404
TI  - Neuroleptic malignant syndrome from central nervous system insult: 4 cases and a
      novel treatment strategy. Clinical article.
AB  - Neuroleptic malignant syndrome (NMS) is a potentially life-threatening entity
      characterized by hyperthermia, autonomic deregulation, decreased mental status,
      increased muscle tone, and, frequently, by renal failure due to rhabdomyolysis.
      Classically, it follows administration of antipsychotic medication. The authors
      report on 4 patients (2 children and 2 adults) in whom NMS was diagnosed after a
      CNS insult. No patient was receiving antipsychotic medication. The patients'
      hospital and clinic charts, radiographic data, and follow-up telephone
      conversations were reviewed retrospectively. All 4 patients met diagnostic
      criteria for NMS. Three patients presented with shunt failure, and 1 patient had
      undergone a functional hemispherectomy 2 days earlier. One patient with shunt
      failure received the diagnosis retrospectively. An endoscopic third
      ventriculostomy alleviated his shunt failure and he remains free of NMS. The
      other 2 patients underwent treatment for shunt failure, but NMS remained. These 2
      patients and the one who had undergone hemispherectomy underwent a trial of
      intrathecal baclofen, and the NMS resolved. Subsequently, an intrathecal baclofen
      infusion device was placed in all 3 patients, and the NMS resolved. The 2
      patients in shunt failure had a lumbar intrathecal baclofen infusion device. The
      patient who had undergone hemispherectomy had an intracranial baclofen catheter.
      Neuroleptic malignant syndrome is a rare, life-threatening disorder that can
      occur without the administration of neuroleptic medications. Alleviation of any
      CNS insult is the first order of treatment. Some patients with persistent
      symptoms of NMS may benefit from intrathecal delivery of baclofen.

PMID- 19772405
TI  - Primary pediatric intraspinal sarcomas. Report of 3 cases.
AB  - Sarcomas that arise from within the spinal canal are rare, particularly within
      the pediatric population. In general, these primary intraspinal sarcomas are
      highly aggressive, posing unique treatment challenges with respect to surgery and
      choice of adjuvant therapy. The goal must be to obtain the most complete
      resection possible to minimize the risk of recurrence and metastasis, while
      preventing potential neurological deficits that may result from aggressive
      surgery. Among these primary intraspinal sarcomas are malignant peripheral nerve
      sheath tumors and members of the Ewing sarcoma family of tumors. The authors
      present 3 cases of unique spinal sarcomas in children-2 malignant peripheral
      nerve sheath tumors in patients without neurofibromatosis and an intradural
      extraosseous Ewing sarcoma arising from the sensory component of a lumbar spinal
      nerve-and discuss their management and outcome with a review of the current
      literature.

PMID- 19772406
TI  - Prevalence of pineal cysts in children and young adults. Clinical article.
AB  - OBJECT: Pineal cysts are a frequent incidental finding on intracranial imaging.
      In adults, the prevalence of pineal cysts is estimated to be 1.1-4.3%. However,
      the prevalence is not well established in younger patients. METHODS: The authors
      retrospectively reviewed a consecutive series of 14,516 patients 25 years of age
      and younger, who underwent brain MR imaging at a single institution over an 11
      year period. In patients identified with pineal cysts, the authors analyzed the
      images according to cyst size, signal characteristics, enhancement pattern, and
      evidence of local mass effect. Patient characteristics including demographics and
      other intracranial diagnoses were collected in the pineal cyst population and
      compared with a randomly selected age- and sex-matched control patient
      population. The data were evaluated using univariate and multivariate logistic
      regression, linear regression, and ANOVA. RESULTS: The authors identified 288
      pineal region cysts (2.0%). The prevalence of pineal cysts was higher in female
      (2.4%) than in male patients (1.5%; p < 0.001). Pineal cysts were identified in
      patients of all ages, with an increased prevalence found in older patients (p <
      0.001). Pineal cyst size was similar for all age and sex groups. CONCLUSIONS:
      Pineal cysts are common in the pediatric population, with an increased prevalence
      in girls and in older patients.

PMID- 19772407
TI  - Osteoid osteomas: intraoperative bone scan-assisted resection. Clinical article.
AB  - OBJECT: Osteoid osteomas (OOs) are benign lesions of the spine, but can cause
      significant pain and spinal deformity in the pediatric population. They are often
      surgically elusive, and may require multiple surgical procedures to ensure
      complete resection. Nuclear medicine intraoperative bone scans (IOBSs) are highly
      sensitive for lesion localization and verification of complete surgical
      extirpation. METHODS: A retrospective review of 20 consecutive patients who had
      undergone resection of a spinal OO at the authors' institution was undertaken. In
      all cases, IOBSs were used for lesion localization and verification of resection.
      Postoperative imaging and clinical follow-up were obtained. RESULTS: The average
      length of follow-up was 56 months, with a range of 8-156 months. Five patients
      had undergone a total of 12 unsuccessful prior procedures for resection at other
      institutions where IOBSs were not used. In these patients, complete resection was
      accomplished with the use of IOBSs at the authors' institution. Of the 15
      patients who presented to this institution with a newly diagnosed OO and who
      underwent IOBS-assisted resection, 14 had complete resection without recurrence.
      One patient, however, was found to have a discrete recurrence adjacent to the
      initial resection bed at the time of follow-up. CONCLUSIONS: Osteoid osteomas are
      benign lesions of the spine, and complete resection is curative. If resection is
      incomplete, then recurrence is likely. The IOBS modality is highly sensitive for
      detecting OO and for guiding complete resection. The IOBS modality should be
      considered as a first-line surgical adjunct in cases of suspected OO.

PMID- 19772408
TI  - Endoscopic transventricular positioning of intracystic catheter for treatment of
      craniopharyngioma. Technical note.
AB  - The intracystic injection of chemo- and radiotherapeutic agents was introduced
      for the treatment of craniopharyngioma to control tumor growth and to delay the
      potentially harmful effects of surgery or radiation therapy. The positioning of
      cyst catheters has been performed by means of direct vision, stereotactically
      guided insertion, and ultrasonographic and ventriculoscopic guidance. The
      insertion of a catheter into the cyst is not devoid of complications, with an
      incidence ranging up to 16%, independent of the surgical technique used. Eight
      patients (mean age 25.8 years) with symptomatic cystic craniopharyngioma were
      treated by means of an endoscopic transventricular approach for the insertion of
      an intracystic catheter for intratumoral therapy with interferon-alpha. A single
      right precoronal bur hole is made, and the frontal horn of the lateral ventricle
      is accessed under neuronavigation guidance. A ventricular catheter with an
      inserted stylet was advanced anterior to the endoscope sheath through the same
      cortical access as the endoscope and was guided under endoscopic view down to the
      cyst dome wall. The coagulated surface of the craniopharyngioma cyst was
      punctured and the tip of the ventricular catheter was advanced; the depth was
      established preoperatively on MR scans and confirmed by neuronavigation guidance.
      The proximal end of the cystic catheter was connected to an access chamber to be
      left in the subcutaneous space, and the endoscope was slowly retracted. The
      authors' experience favors the use of neuroendoscopic positioning of intracystic
      catheters as safer than open and stereotactic approaches.

PMID- 19772409
TI  - Forniceal glioma in children. Clinical article.
AB  - OBJECT: Five to ten percent of pediatric brain tumors are located in the
      ventricles. Among them, forniceal lesions are rare and their management has not
      often been described. The aim of this study was to review the clinical,
      radiological, and histopathological features as well as the feasibility of
      surgical excision and the outcomes in these patients. METHODS: From a
      retrospective analysis of 250 cases of supratentorial pediatric glioma, the
      records of 8 children presenting with forniceal lesions were selected and
      reviewed. RESULTS: The median age of patients in the cohort was 13.5 years.
      Presenting features included intracranial hypertension (7 cases), hypothalamic
      dysfunction (2), and memory dysfunction (3). Complete resection was possible in
      only 1 case, where the lesion was mainly exophytic; the remaining patients had
      either a partial resection or biopsy. On histological review, the tumors were
      confirmed as pilocytic astrocytoma (4 lesions), WHO Grade II astrocytoma (3), and
      ganglioglioma (1). Postoperatively, working and retrograde memory was normal for
      all patients, but the authors found a mild alteration in verbal episodic memory
      in 5 patients. Despite fatigability for 5 patients, academic achievement was
      normal for all but 2, both of whom had preoperative school difficulties.
      Additional treatment was required for 5 patients for tumor progression, with a
      median interval of 19 months from surgery. At a median follow-up duration of 4.9
      years, all patients had stable disease. CONCLUSIONS: In this series, forniceal
      gliomas were found to be low-grade gliomas. They are surgically challenging, and
      only exophytic lesions may be cured surgically. Due to the high rate of
      progression of residual disease, adjuvant therapy is recommended for infiltrative
      tumors, and it yielded excellent results.

PMID- 19772410
TI  - Survival and functional outcome of childhood spinal cord low-grade gliomas.
      Clinical article.
AB  - OBJECT: Intramedullary spinal cord low-grade gliomas (LGGs) are rare CNS
      neoplasms in pediatric patients, and there is little information on therapy for
      and outcome of these tumors in this population. Furthermore, most patient series
      combine adult and pediatric patients or high- and low-grade tumors, resulting in
      controversial data regarding optimal treatment of these children. To clarify
      these issues, the authors performed a regional population-based study of spinal
      cord LGGs in pediatric patients. METHODS: All pediatric patients with LGGs
      treated during the MR imaging era (1985-2007) were identified in the
      comprehensive database of the Hospital for Sick Children in Toronto. Data on
      demographics, pathology, treatment details, and outcomes were collected. RESULTS:
      Spinal cord LGGs in pediatric patients constituted 29 (4.6%) of 635 LGGs.
      Epidemiological and clinical data in this cohort were different than in patients
      with other spinal tumors and strikingly similar to data from pediatric patients
      with intracranial LGGs. The authors observed an age peak at 2 years and a male
      predominance in patients with these tumors. Histological testing revealed a Grade
      I astrocytoma in 86% of tumors. Although 5-year progression-free survival for the
      entire group was 48 +/- 9%, all patients were alive at a median follow-up of 8.2
      years. Five-year progression-free survival was 88 +/- 13% for patients undergoing
      gross-total resection and 34 +/- 11% for those undergoing all other therapies,
      respectively (p = 0.02). Chemotherapy and radiation therapy showed similar
      efficacy, achieving sustained tumor control in most patients. However, this
      excellent survival rate was associated with an 83% rate of significant
      neurological and orthopedic sequelae. CONCLUSIONS: This study provides basic data
      on the incidence, clinical course, and outcome of spinal cord LGGs in pediatric
      patients. The similarities between spinal and intracranial LGGs in pediatric
      patients showing excellent survival but high morbidity suggest that a less
      aggressive approach may be the preferable treatment option for these patients.

PMID- 19772411
TI  - Combined endoscopic-microsurgical approach for transsphenoidal (sphenopalatine)
      encephalocele with an intralesional pituitary gland. Case report.
AB  - The treatment of the transsphenoidal sphenopalatine encephalocele in infants has
      not been thoroughly described in the literature. Pterional and subfrontal
      transbasal approaches have been reported as the advised treatment for
      transethmoidal encephalocele, but their feasibility for transsphenoidal
      encephalocele remains controversial, particularly in neonates. The potential harm
      to vital structures within the herniated tissue and intraoperative bleeding have
      been considered the major cause of poor postoperative results. The authors
      present the case of a full-term newborn with a cleft palate and a large
      transsphenoidal sphenopalatine encephalocele, which filled the nasopharyngeal
      space and provided MR imaging evidence of an intralesional pituitary gland. The
      lesion is unusual, and the extracranial intraoral endoscopic approach with an
      optimal outcome and sparing of the pituitary tissue has never been described in
      detail in an infant of this age.

PMID- 19772412
TI  - Successful treatment of severe cerebral vasospasm following hemorrhage of an
      arteriovenous malformation. Case report.
AB  - The authors describe the case of a 13-year-old boy who presented with an
      intraventricular hemorrhage caused by a left trigonal arteriovenous malformation.
      After an initial recovery, the patient experienced complete right-sided paresis
      on posthemorrhage Day 6. Severe cerebral vasospasm was found on MR angiography
      and confirmed on conventional cerebral angiography. Intraarterial nicardipine
      injection and balloon angioplasty were successfully performed with improved
      vasospasm and subsequent neurological recovery. Cerebral vasospasm should be
      considered in the differential diagnosis for neurological deterioration following
      an arteriovenous malformation hemorrhage, and aggressive treatment can be
      administered to prevent ischemia and further neurological deficits.

PMID- 19772413
TI  - Pediatric tethered cord syndrome: response of scoliosis to untethering
      procedures. Clinical article.
AB  - OBJECT: Tethered cord syndrome (TCS) is frequently associated with scoliosis in
      the pediatric population. Following spinal cord untethering, many patients
      continue to experience progression of spinal deformity. However, the incidence
      rate, time course, and risk factors for scoliosis progression following tethered
      cord release remain unclear. The aim of this study was to determine factors
      associated with scoliosis progression and whether tethered cord release alone
      would halt curve progression in pediatric TCS. METHODS: The authors
      retrospectively reviewed 27 consecutive pediatric cases of spinal cord
      untethering associated with scoliosis. The incidence rate and factors associated
      with scoliosis progression (> 10 degrees increased Cobb angle) after untethering
      were evaluated using the Kaplan-Meier method. RESULTS: The mean age of the
      patients was 8.9 years. All patients underwent cord untethering for lower
      extremity weakness, back and leg pain, or bowel and bladder changes. Mean +/- SD
      of the Cobb angle at presentation was 41 +/- 16 degrees . The cause of the spinal
      cord tethering included previous myelomeningocele repair in 14 patients (52%),
      fatty filum in 5 (18.5%), lipomeningocele in 3 (11%), diastematomyelia in 2
      (7.4%), arthrogryposis in 1 (3.7%), imperforate anus with an S-2 hemivertebra in
      1 (3.7%), and lipomyelomeningocele with occult dysraphism in 1 (3.7%). Mean
      follow-up was 6 +/- 2 years. Twelve patients (44%) experienced scoliosis
      progression occurring a median of 2.4 years postoperatively and 8 (30%) required
      subsequent fusion for progression. At the time of untethering, scoliosis < 40
      degrees was associated with a 32% incidence of progression, whereas scoliosis >
      40 degrees was associated with a 75% incidence of progression (p < 0.01).
      Patients with Risser Grades 0-2 were also more likely to experience scoliosis
      progression compared with Risser Grades 3-5 (p < 0.05). Whereas nearly all
      patients with Risser Grades 0-2 with curves > 40 degrees showed scoliosis
      progression (83%), 54% of patients with Risser Grades 0-2 with curves < 40
      degrees progressed, and no patients with Risser Grades 3-5 with curves < 40
      degrees progressed following spinal cord untethering. CONCLUSIONS: In this
      experience with pediatric TCS-associated scoliosis, patients with Risser Grades 3
      5 and Cobb angles < 40 degrees did not experience curve progression after
      tethered cord release. Patients with Risser Grades 0-2 and Cobb angles > 40
      degrees were at greatest risk of curve progression after cord untethering.
      Pediatric patients with TCS-associated scoliosis should be monitored closely for
      curve progression using standing radiographs after spinal cord untethering,
      particularly those with curves > 40 degrees or who have Risser Grades 0-2.

PMID- 19772414
TI  - Urological outcome following multiple repeat spinal cord untethering operations.
      Clinical article.
AB  - OBJECT: Patients who have undergone myelomeningocele or lipomyelomeningocele
      repair may present with symptomatic retethering of the spinal cord. The authors
      describe the results as well as the utility of urological testing in pediatric
      patients undergoing multiple repeat untethering operations. METHODS: The authors
      reviewed the records of 13 patients with lipomyelomeningocele or myelomeningocele
      who underwent at least 2 untethering procedures after their initial repair and
      who had urodynamic testing within 6 months prior to and 6 months following each
      untethering operation. In each case, urological testing included a slow-fill
      cystometrogram and an external urethral sphincter electromyogram using a
      concentric needle electrode to analyze individual motor unit action potentials at
      rest, in response to sacral reflexes, and during bladder filling and emptying.
      RESULTS: New urinary symptoms were identified in 7 of 13 cases prior to surgery.
      Postoperative subjective improvement in urinary symptoms was noted in 5 of these
      7 cases. Improvement in bladder function on urodynamic testing correlated with
      symptomatic improvement. Sphincter electromyography findings did not correlate
      with changes in preoperative symptoms or postoperative improvement. CONCLUSIONS:
      In patients undergoing multiple repeat spinal cord untethering operations,
      measuring bladder function is more useful than sphincter electromyographty when
      selecting candidates for surgery and for measuring surgical outcomes.

PMID- 19772415
TI  - A new fiber-mediated carbon dioxide laser facilitates pediatric spinal cord
      detethering. Technical note.
AB  - OBJECT: The authors report their experience with a novel flexible fiber capable
      of transmitting CO(2) laser energy during spinal cord tumor resection and
      detethering. METHODS: A fiber optic system capable of transmitting CO(2) laser
      energy was used in the detethering of the spinal cord in 3 cases. The first case
      involved a 9-year-old girl with a terminal lipoma. The second case was an 11
      month-old boy with a thoracic intramedullary dermoid and dermal sinus tract. The
      third case involved a 13-year-old girl suffering from a tethered spinal cord
      subsequent to a previously repaired myelomeningocele. RESULTS: In all 3 cases,
      the new fiber CO(2) laser technology allowed the surgeon to perform microsurgical
      dissection while sparing adjacent neurovascular structures without time-consuming
      setup. The system was easy to implement, more ergonomic than previous
      technologies, and safe. The CO(2) laser provided the ability to cut and coagulate
      while sparing adjacent tissue because of minimal energy dispersion and ease of
      use, without the articulating arms involved in the prior generation of lasers.
      CONCLUSIONS: Using a flexible fiber to conduct CO(2) laser energy allows accurate
      microneurosurgical dissection and renders this instrument a high-precision and
      ergonomic surgical tool in the setting of spinal cord detethering.

PMID- 19772416
TI  - Risk factors for latex sensitization in young children with myelomeningocele.
      Clinical article.
AB  - OBJECT: Patients with myelomeningoceles (MMCs) are at increased risk of latex
      allergy and sensitization. Number of surgeries and history of atopy are known
      risk factors. The object of this study was to evaluate the role of diagnostic
      procedures and nonsurgical treatments in latex sensitization in young patients
      with MMC. METHODS: Seventy-three children with MMC were included in the study.
      For each child a questionnaire was administered and serum determination of IgE
      was performed, and 62 children underwent skin prick tests (SPTs), 60 of which had
      reliable results. Multivariate logistic regression modeling was performed, using
      latex sensitization as the dependent variable. RESULTS: The mean age of the 73
      patients was 3.8 years. The SPT results were positive in 30.6%, whereas results
      of testing for latex-specific IgE were positive in only 8.2%. In univariate
      analysis, history of untethering, barium enema, and number of clean intermittent
      catheterizations (CICs) per day were significantly associated with positive
      results on the SPT. Although the number of surgical procedures was significantly
      higher in patients who had shunts, no significant relationship between the
      presence of a shunt and latex sensitization was seen. CONCLUSIONS: The young age
      of the patients in this study may account for the low prevalence of latex
      sensitization that was found. In young patients with MMC, the numbers of CICs per
      day, a history of untethering, circumcision, and a barium enema performed without
      latex-free equipment could be risk factors for latex sensitization. The use of
      latex-free gloves in all procedures performed in these cases, nonlatex polyvinyl
      chloride catheters in CIC, and ordinary nonballoon tips in barium enemas could
      decrease the risk of sensitization.

PMID- 19772417
TI  - Experiences with a gravity-assisted valve in hydrocephalic children. Clinical
      article.
AB  - OBJECT: Over the past decade, a gravity-assisted valve (GAV) has become a
      standard device in many European pediatric hydrocephalus centers. Because past
      comparative clinical outcome studies on valve design have not included any GAV,
      the authors in this trial evaluated the early results of GAV applications in a
      pediatric population. METHODS: For a minimum of 2 years the authors monitored 169
      of 182 hydrocephalic children who received a pediatric GAV at their first CSF
      shunt insertion (61.5%) or as a substitute for any differential pressure valve
      (38.5%) at 1 of 7 European pediatric hydrocephalus centers. Outcomes were
      categorized as valve survival (primary outcome) or shunt survival (secondary
      outcome). The end point was defined as valve explantation. RESULTS: Within a
      follow-up period of 2 years, the valve remained functional in 130 (76.9%) of 169
      patients. One hundred eight of these patients (63.9%) had an uncomplicated
      clinical course without any subsequent surgery, and 22 (13%) were submitted to a
      valve-preserving catheter revision without any further complications during the
      follow-up period. Thirty-nine patients (23.1%) reached an end point of valve
      explantation: 13 valve failures from infection (7.7%), 8 (4.7%) from
      overdrainage, and 18 (10.6%) from underdrainage. CONCLUSIONS: Compared with
      nongravitational shunt designs, a GAV does not substantially affect the early
      complication rate. Valve-preserving shunt revisions do not increase the risk of
      subsequent valve failure and therefore should not be defined as an end point in
      studies on valve design. A significant impact of any well-established valve
      design on the early complication rate in shunt surgery is not supported by any
      current data; therefore, this correlation should be dismissed. As overdrainage
      related complications have been shown to occur late, the presumed advantages of a
      pediatric GAV remain to be shown in a long-term study.

PMID- 19772418
TI  - Synchronous parathyroid and papillary thyroid carcinomas.

PMID- 19772419
TI  - Recurrence after treatment of micropapillary thyroid cancer.
AB  - BACKGROUND: Despite very low mortality associated with micropapillary thyroid
      cancer, locoregional recurrence is common and controversy exists regarding
      optimal surgical treatment and the role of adjunctive radioiodine. METHODS: The
      National Thyroid Cancer Treatment Cooperative Study Group Registry was analyzed
      for recurrences in patients with unifocal versus multifocal micropapillary
      cancer, with or without nodal disease, depending upon the extent of surgery and
      the use of adjunctive radioiodine. Six hundred eleven patients considered disease
      free after initial therapy were followed for 2572 person-years. RESULTS: Thirty
      patients (6.2%) had recurrences detected at a mean 2.8 years after primary
      treatment. Recurrences did not differ between patients with unifocal and
      multifocal disease overall; however, among patients who received less than a near
      total thyroidectomy (NTT), those with multifocal disease had more recurrences
      than those with unifocal disease (18% vs. 4%, p = 0.01). Patients with multifocal
      disease who had a total (T) or NTT trended toward fewer recurrences than those
      undergoing less than an NTT (6% vs. 18%, p = 0.058). In patients who did not
      receive radioiodine therapy, recurrence was more common in patients with
      multifocal disease versus unifocal disease (7% vs. 2%, p = 0.02). However,
      radioiodine did not reduce recurrences in patients with multifocal disease or
      patients with positive nodes. Patients with positive nodes had more recurrences
      than node-negative patients regardless of surgical extent or use of radioiodine.
      CONCLUSIONS: Patients with micropapillary multifocal disease have a reduced risk
      of recurrence after a T/NTT compared with less surgery. A randomized, controlled
      trial is necessary and feasible to determine if radioiodine ablation of thyroid
      remnants is advantageous in patients with intrathyroidal micropapillary cancer.

PMID- 19772422
TI  - Common variants in the G protein beta3 subunit gene and thyroid disorders in a
      formerly iodine-deficient population.
AB  - BACKGROUND: Heterotrimeric G proteins are key mediators of signals from membrane
      receptors-including the thyroid-stimulating hormone (TSH) receptor-to cellular
      effectors. Gain-of-function mutations in the TSH receptor and the Galpha(S)
      subunit occur frequently in hyperfunctioning thyroid nodules and differentiated
      thyroid carcinomas, whereby the T allele of a common polymorphism (825C>T,
      rs5443) in the G protein beta3 subunit gene (GNB3) is associated with increased G
      protein-mediated signal transduction and a complex phenotype. The aim of this
      study was to investigate whether this common polymorphism affects key parameters
      of thyroid function and morphology and influences the pathogenesis of thyroid
      diseases in the general population. METHODS: The population-based cross-sectional
      Study of Health in Pomerania is a general health survey with focus on thyroid
      diseases in northeast Germany, a formerly iodine-deficient area. Data from 3428
      subjects (1800 men and 1628 women) were analyzed for an association of the GNB3
      genotype with TSH, free triiodothyronine and thyroxine levels, urine iodine and
      thiocyanate excretion, and thyroid ultrasound morphology including thyroid
      volume, presence of goiter, and thyroid nodules. RESULTS: There was no
      association between GNB3 genotype status and the functional or morphological
      thyroid parameters investigated, neither in crude analyses nor upon multivariable
      analyses including known confounders of thyroid disorders. CONCLUSIONS: Based on
      the data from this large population-based survey, we conclude that the GNB3
      825C>T polymorphism does not affect key parameters of thyroid function and
      morphology in the general population of a formerly iodine-deficient area.

PMID- 19772423
TI  - Early recurrence of papillary and follicular thyroid carcinoma predicts a worse
      outcome.
AB  - BACKGROUND: The occurrence of recurrent papillary and follicular thyroid
      carcinomas is not unusual. Numerous studies have reported the association between
      risk factors of initial surgery and recurrence of papillary and follicular
      thyroid carcinomas. However, we do not have sufficient data to analyze the time
      of postoperative recurrence associated with therapeutic results and cancer
      mortality. We hypothesized that an early recurrence of papillary and follicular
      thyroid cancers implies a rapid growth of cancer resulting in high mortality
      rate. METHODS: We conducted a retrospective study in a medical center in northern
      Taiwan. The investigation included 2148 cases of papillary and follicular thyroid
      carcinoma, including 325 recurrent cases during the period between 1977 and 2006.
      The studied cases were categorized into early or late recurrence groups. Cases
      with an early recurrence were defined as those in which recurrence occurred in
      the first year following thyroid surgery. RESULTS: Tumor size, radioactive iodide
      treatment, multifocality, and tumor-node metastasis stage were independent
      predictors of recurrence. After a mean follow-up of 8.7 +/- 0.1 years, death due
      to thyroid cancer was observed to occur in 105 (32.3%) recurrent cases. Among the
      325 recurrent cases, early recurrence was detected in 185 cases, and late
      recurrence was detected in 140 cases. Early recurrence was mostly observed in
      older male patients; a high mortality rate was associated with these cases.
      Distant metastases were observed in about 80% of the cases in the early
      recurrence group, whereas localized metastases in the neck region were observed
      in more than half the cases in the late recurrence group. The percentage of
      patients with a non-disease-free status and distant metastases in the early
      recurrence group was higher than that in the late recurrence group. The 10-year
      disease-specific survival rates were 52.5% and 85.1% for the early and late
      recurrence groups, respectively. CONCLUSIONS: Early recurrent papillary and
      follicular thyroid carcinomas are associated with high mortalities. Tumor size
      and multifocality deserve consideration as indicators of recurrence. Therefore,
      patients whose primary follicular or papillary thyroid carcinoma has features
      associated with early recurrence should probably receive more aggressive initial
      treatment.

PMID- 19772428
TI  - Association of polymorphisms in genes of the homologous recombination DNA repair
      pathway and thyroid cancer risk.
AB  - BACKGROUND: Ionizing radiation exposure has been pointed out as a risk factor for
      thyroid cancer. The double-strand breaks induced by this carcinogen are usually
      repaired by homologous recombination repair pathway, a pathway that includes
      several polymorphic genes. Since there is a scarcity of data about the
      involvement of these gene polymorphisms in thyroid cancer susceptibility, we
      carried out a case-control study in a Caucasian Portuguese population. METHODS:
      We genotyped 109 patients and 217 controls for the XRCC3 T241M, XRCC2 R188H, NBS1
      E185Q, and RAD51 Ex1-59G>T polymorphisms to evaluate their potential main effects
      on risk for this pathology. RESULTS: The results obtained showed that for the
      RAD51 Ex1-59G>T polymorphism, the homozigosity for the variant allele was
      associated with an almost significant increase of the odds ratio (OR) (adjusted
      OR = 1.9; confidence interval 95%: 1.0-3.5; p = 0.057). Additionaly, when the
      XRCC3 T241M data were analyzed concerning the presence of at least one wild-type
      allele, we observed that individuals homozygous for the variant allele had a
      higher risk for thyroid cancer (adjusted OR = 2.0; confidence interval 95%: 1.1
      3.6; p = 0.026). When the data were analyzed according to the number of RAD51 Ex1
      59G>T and XRCC3 T241M variant alleles, the coexistence of three or more variant
      alleles in either gene was associated to a significant higher risk (three variant
      alleles: adjusted OR = 2.9, p = 0.036; four variant alleles: adjusted OR = 8.0, p
      = 0.006). CONCLUSIONS: Since XRCC3 is involved in the assembly and stabilization
      of RAD51 protein multimers at double-strand break sites, we cannot exclude that
      the interaction of both polymorphisms can lead to a decreased DNA repair capacity
      and consequently increased risk for thyroid cancer.

PMID- 19772429
TI  - A novel orthotopic mouse model of human anaplastic thyroid carcinoma.
AB  - BACKGROUND: Orthotopic mouse models of human cancer represent an important in
      vivo tool for drug testing and validation. Most of the human thyroid carcinoma
      cell lines used in orthotopic or subcutaneous models are likely of melanoma and
      colon cancer. Here, we report and characterize a novel orthotopic model of human
      thyroid carcinoma using a unique thyroid cancer cell line. METHODS: We used the
      cell line 8505c, originated from a thyroid tumor histologically characterized by
      anaplastic carcinoma cell features. We injected 8505c cells engineered using a
      green fluorescent protein-positive lentiviral vector orthotopically into the
      thyroid of severe combined immunodeficient mice. RESULTS: Orthotopic implantation
      with the 8505c cells produced thyroid tumors after 5 weeks, showing large neck
      masses, with histopathologic features of a high-grade neoplasm (anaplasia,
      necrosis, high mitotic and proliferative indexes, p53 positivity, extrathyroidal
      invasion, lymph node and distant metastases) and immunoprofile of follicular
      thyroid cell origin with positivity for thyroid transcription factor-1 and PAX8,
      and for cytokeratins. CONCLUSIONS: Here we describe a novel orthotopic thyroid
      carcinoma model using 8505c cells. This model can prove to be a reliable and
      useful tool to investigate in vivo biological mechanisms determining thyroid
      cancer aggressiveness, and to test novel therapeutics for the treatment of
      refractory or advanced thyroid cancers.

PMID- 19772430
TI  - Mild decreases in white blood cell and platelet counts are present one year after
      radioactive iodine remnant ablation.
AB  - BACKGROUND: Bone marrow suppression after multiple, high-dose radioactive iodine
      (RAI) therapies is well described. However, changes in the peripheral complete
      blood count (CBC) that may occur after a single treatment of RAI such as that
      commonly used for routine remnant ablation is much less well studied. In this
      retrospective trial, we examined the rate of persistent anemia, leukopenia, and
      thrombocytopenia 1 year after a single RAI administration. METHODS: Peripheral
      blood counts at baseline were compared to those obtained 1 year after RAI remnant
      ablation in 206 consecutive thyroid cancer patients. Analyses were performed to
      determine the potential impact of both the method of preparation (recombinant
      human thyroid stimulating hormone [rhTSH] vs. thyroid hormone withdrawal) and
      administered activity of (131)I on hemoglobin, white blood cell (WBC), and
      platelet counts. RESULTS: Comparison of the baseline CBC before RAI ablation
      (median administered activity of approximately 3700 MBq or 100 mCi) with the
      follow-up CBC done 1 year later demonstrated a statistically significant decline
      in total WBC (6.7 +/- 2.1 x 10(9) vs. 6.0 +/- 1.8 x 10(9)/L, p < 0.001; 9.7%
      below the reference range at 1-year follow-up) and platelet (272 +/- 67 vs. 250
      +/- 65 x 10(9)/L, p < 0.001; 5.8% below the reference range at 1-year follow-up)
      with no significant change in hemoglobin (1.40 +/- 0.14 vs. 1.40 +/- 0.14 g/L or
      14.0 +/- 1.4 vs. 14.0 +/- 1.4 g/dL; 1.5% below the reference range at 1-year
      follow-up). There were no significant clinical complications observed during the
      1-year follow-up period. The changes in total WBC and platelets were not related
      to the method of preparation or the administered activity of RAI. CONCLUSION: A
      single RAI treatment of approximately 3700 MBq (100 mCi) after thyroidectomy is
      associated with a statistically significant, mild decline in WBC and platelet
      counts that persists for at least 1 year after ablation. Given the small
      magnitude of the changes and the lack of clinically significant adverse events,
      these observations should not decrease the use of RAI ablation in moderate to
      high-risk patients in whom the benefits of ablation are likely to outweigh these
      minor risks.

PMID- 19772432
TI  - A note on the linear memory baum-welch algorithm.
AB  - We demonstrate the simplicity and generality of the recently introduced linear
      space Baum-Welch algorithm for hidden Markov models. We also point to previous
      literature on the subject.

PMID- 19772431
TI  - Accurate stochastic simulation via the step anticipation tau-leaping (SAL)
      algorithm.
AB  - Stochastic simulation methods are important in modeling chemical reactions, and
      biological and physical stochastic processes describable as continuous-time
      discrete-state Markov chains with a finite number of reactant species and
      reactions. The current algorithm of choice, tau-leaping, achieves fast and
      accurate stochastic simulation by taking large time steps that leap over
      individual reactions. During a leap interval (t, t + tau) in tau-leaping, each
      reaction channel operates as a Poisson process with a constant intensity. We
      modify tau-leaping to allow linear and quadratic changes in reaction intensities.
      Because our version of tau-leaping accurately anticipates how intensities change
      over time, we propose calling it the step anticipation tau-leaping (SAL)
      algorithm. We apply SAL to four examples: Kendall's process, a two-type branching
      process, Ehrenfest's model of diffusion, and Michaelis-Menten enzyme kinetics. In
      each case, SAL is more accurate than ordinary tau-leaping. The degree of
      improvement varies with the situation. Near stochastic equilibrium, reaction
      intensities are roughly constant, and SAL and ordinary tau-leaping perform about
      equally well.

PMID- 19772433
TI  - A new data mining approach for the detection of bacterial promoters combining
      stochastic and combinatorial methods.
AB  - We present a new data mining method based on stochastic analysis (Hidden Markov
      Model [HMM]) and combinatorial methods for discovering new transcriptional
      factors in bacterial genome sequences. Sigma factor binding sites (SFBSs) were
      described as patterns of box1-spacer-box2 corresponding to the -35 and -10 DNA
      motifs of bacterial promoters. We used a high-order HMM in which the hidden
      process is a second-order HMM chain. Applied on the genome of the model bacterium
      Streptomyces coelicolor A3(2), the a posteriori state probabilities revealed
      local maxima or peaks whose distribution was enriched in the intergenic sequences
      ("iPeaks" for intergenic peaks). Short DNA sequences underlying the iPeaks were
      extracted and clustered by a hierarchical classification algorithm based on the
      SmithWaterman local similarity. Some selected motif consensuses were used as box1
      (-35 motif ) in the search of a potential neighbouring box2 (-10 motif ) using a
      word enumeration algorithm. This new SFBS mining methodology applied on
      Streptomyces coelicolor was successful to retrieve already known SFBSs and to
      suggest new potential transcriptional factor binding sites (TFBSs). The well
      defined SigR regulon (oxidative stress response) was also used as a test quorum
      to compare first- and second-order HMM. Our approach also allowed the preliminary
      detection of known SFBSs in Bacillus subtilis.

PMID- 19772434
TI  - Inference in signal transduction pathways using em algorithm and an implicit
      algorithm: incomplete data case.
AB  - We summarize here the Implicit statistical inference approach as an alternative
      to Bayesian networks and we give an effective iterative algorithm analogous to
      the Expectation Maximization algorithm to infer signal transduction network when
      the set of data is incomplete. We proved the convergence of our algorithm that we
      called Implicit algorithm and we apply it to simulated data for a simplified
      signal transduction pathway of the EGFR protein.

PMID- 19772435
TI  - Sparsity optimization method for multivariate feature screening for gene
      expression analysis.
AB  - Constructing features from high-dimensional gene expression data is a critically
      important task for monitoring and predicting patients' diseases, or for knowledge
      discovery in computational molecular biology. The features need to capture the
      essential characteristics of the data to be maximally distinguishable. Moreover,
      the essential features usually lie in small or extremely low-dimensional
      subspaces, and it is crucial to find them for knowledge discovery and pattern
      classification. We present a computational method for extracting small or even
      extremely low-dimensional subspaces for multivariate feature screening and gene
      expression analysis using sparse optimization techniques. After we transform the
      feature screening problem into a convex optimization problem, we develop an
      efficient primal-dual interior-point method expressively for solving large-scale
      problems. The effectiveness of our method is confirmed by our experimental
      results. The computer programs will be publicly available.

PMID- 19772436
TI  - Duplication mechanism and disruptions in flanking regions determine the fate of
      Mammalian gene duplicates.
AB  - Here we identify duplicated genes in five mammalian genomes and classify these
      duplicates based on the mechanisms by which they were generated.
      Retrotransposition accounts for at least half of all predicted duplicate genes in
      these genomes, with tandem and interspersed DNA-mediated duplicates comprising
      the other half. Estimation of the evolutionary rates in each class revealed
      greater rate asymmetry between retrotransposed and interspersed DNA duplicate
      pairs than between tandem duplicates, suggesting that retrotransposed and
      interspersed DNA duplicates are diverging more quickly. In an attempt to
      understand the basis of this asymmetry, we identified disruption of flanking DNA
      as an indicator of new duplicate fate-loss of local synteny accelerates the
      asymmetry of divergence of interspersed DNA duplicates. We also show that intact
      retrogenes are enriched in intergenic regions and indel purified regions of the
      human genome. Moreover, intact retrogenes closest to annotated genes show the
      greatest levels of purifying selective pressure. Together, these findings suggest
      that the differential evolution of duplicate genes may be significantly
      influenced by changes in local genome architecture.

PMID- 19772437
TI  - Mining the semantics of genome super-blocks to infer ancestral architectures.
AB  - The study of evolutionary mechanisms is made more and more accurate by the
      increase in the number of fully sequenced genomes. One of the main problems is to
      reconstruct plausible ancestral genome architectures based on the comparison of
      contemporary genomes. Current methods have largely focused on finding complete
      architectures for ancestral genomes, and, due to the computational difficulty of
      the problem, stop after a small number of equivalent minimal solutions have been
      found. Recent results suggest, however, that the set of minimum complete
      architectures is very large and heterogeneous. In fact these solutions are
      collections of conserved blocks, freely rearranged. In this paper, we identify
      these conserved super-blocks, using a new method of analysis of ancestral
      architectures that reconciles both breakpoint and rearrangement analyses, as well
      as respects biological constraints. The resulting algorithms permit the first
      reliable reconstruction of plausible ancestral architectures for several non-WGD
      yeasts simultaneously, a problem hitherto intractable due to the extensive map
      reshuffling of these species. See online Supplementary Material at
      www.liebertonline.com.

PMID- 19772438
TI  - Adolescent pornographic internet site use: a multivariate regression analysis of
      the predictive factors of use and psychosocial implications.
AB  - The study objectives were to evaluate the prevalence, predictors, and
      implications of pornographic Internet site (PIS) use among Greek adolescents. A
      cross-sectional study was conducted among 529 randomly selected Greek high school
      students. The prevalence of overall PIS use was 19.47% (n = 96). Among PIS users,
      55 (57.29%) reported infrequent and 41 (42.71%) reported frequent PIS use. The
      predictors of infrequent PIS use included male gender (adjusted odds ratio [AOR]
      = 8.33; 95% confidence interval [CI] = 3.52-19.61), Internet use for sexual
      education (AOR = 5.26; 95% CI = 1.78-15.55), chat rooms (AOR = 2.95; 95% CI =
      1.48-5.91), and purchases (AOR = 3.06; 95% CI = 1.22-7.67). The predictors of
      frequent PIS use were male gender (AOR = 19.61; 95% CI = 4.46-83.33), Internet
      use for sexual education (AOR = 7.39; 95% CI = 2.37-23.00), and less than 10
      hours per week Internet use (AOR = 1.32; 95% CI = 1.10-1.59). Compared to non-PIS
      users, infrequent PIS users were twice as likely to have abnormal conduct
      problems (odds ratio [OR] = 2.74; 95% CI = 1.19-6.28); frequent PIS users were
      significantly more likely to have abnormal conduct problems (OR = 4.05; 95% CI =
      1.57-10.46) and borderline prosocial score (OR = 4.22; 95% CI = 1.64-10.85).
      Thus, both infrequent and frequent PIS use are prevalent and significantly
      associated with social maladjustment among Greek adolescents.

PMID- 19772439
TI  - The good-genes and compatible-genes benefits of mate choice.
AB  - Genetic benefits from mate choice could be attained by choosing mates with high
      heritable quality ("good genes") and that are genetically compatible ("compatible
      genes"). We clarify the conceptual and empirical framework for estimating genetic
      benefits of mate choice, stressing that benefits must be measured from offspring
      fitness because there are no unequivocal surrogates for genetic quality of
      individuals or for compatibility of parents. We detail the relationship between
      genetic benefits and additive and nonadditive genetic variance in fitness,
      showing that the benefits have been overestimated in previous verbal treatments.
      We point out that additive benefits readily arise from nonadditive gene action
      and that the idea of "heritable nonadditive benefits" is a misconception. We
      review the empirical evidence of the magnitude of benefits of good genes and
      compatible genes in animal populations, and we outline the most promising future
      directions for empirical research on the genetic benefits of mate choice.

PMID- 19772440
TI  - Brain training for silver gamers: effects of age and game form on effectiveness,
      efficiency, self-assessment, and gameplay experience.
AB  - In recent years, an aging demographic majority in the Western world has come to
      the attention of the game industry. The recently released "brain-training" games
      target this population, and research investigating gameplay experience of the
      elderly using this game form is lacking. This study employs a 2 x 2 mixed
      factorial design (age group: young and old x game form: paper and Nintendo DS) to
      investigate effects of age and game form on usability, self-assessment, and
      gameplay experience in a supervised field study. Effectiveness was evaluated in
      task completion time, efficiency as error rate, together with self-assessment
      measures (arousal, pleasure, dominance) and game experience (challenge, flow,
      competence, tension, positive and negative affect). Results indicate players,
      regardless of age, are more effective and efficient using pen-and-paper than
      using a Nintendo DS console. However, the game is more arousing and induces a
      heightened sense of flow in digital form for gamers of all ages. Logic problem
      solving challenges within digital games may be associated with positive feelings
      for the elderly but with negative feelings for the young. Thus, digital logic
      training games may provide positive gameplay experience for an aging Western
      civilization.

PMID- 19772441
TI  - The effects of customers' mobile experience and technical support on the
      intention to use mobile banking.
AB  - While mobile banking has become an integral part of banking activities, it has
      also caused systems-related stress and consequent distrust among mobile banking
      users. This study looks into the phenomenon of technology adoption for mobile
      banking users and identifies potential factors that nurture positive intentions
      toward mobile banking usage. It examines the effects of a customer's mobile
      experience and technical support on mobile banking acceptance and explains how
      some variables affect this intention. After a literature review, the method of
      empirical analysis using a structured questionnaire is developed. Hierarchical
      Moderated Regression Analyses (HMRA) is used to examine the model. We find that
      mobile experience and technical support tend to strengthen the relationship
      between technological characteristics and a customer's intention to use the
      mobile technology.

PMID- 19772442
TI  - Having to versus wanting to play: background and consequences of harmonious
      versus obsessive engagement in video games.
AB  - The present research examined the background and consequences of different styles
      of engagement in video game play. Based on self-determination theory(1) and the
      dualistic model of passion,(2) the authors hypothesized that high levels of basic
      psychological need satisfaction would foster harmonious passion for video play,
      supporting the subjective sense that play is something one wants to do. It was
      also predicted that low levels of need satisfaction would promote obsessive
      passion for games and contribute to the feeling that game play is something one
      feels compelled to or has to do. It was expected, in turn, that passion for play
      would directly influence player outcomes closely tied to games, moderate links
      between play and well-being, and relate to overall levels of well-being as a
      function of basic need satisfaction. As expected, results showed that low levels
      of basic need satisfaction were associated with more obsessive passion, higher
      amounts of play, greater tension following play, and low game enjoyment, whereas
      high levels of need satisfaction did not predict hours of play but were
      associated with more harmonious passion, game enjoyment, and energy following
      play. Moderation analyses showed that high amounts of play related negatively to
      well-being only to the extent that players reported an obsessive passion and that
      the unique relations between passion and overall levels of player well-being were
      quite small once controlling for their basic need satisfaction in daily life.
      Discussion of the current findings focuses on their significance for
      understanding disordered play and the value of applying a theory-based approach
      to study motivation for virtual contexts.

PMID- 19772443
TI  - Highlights from the october 2009 issue of DNA and cell biology.

PMID- 19772444
TI  - Insulin delivery via lungs-is it still possible?

PMID- 19772445
TI  - Efficacy and safety of AIR inhaled insulin compared to insulin lispro in patients
      with type 1 diabetes mellitus in a 6-month, randomized, noninferiority trial.
AB  - BACKGROUND: Patients with type 1 diabetes may prefer features of AIR inhaled
      insulin (developed by Alkermes, Inc. [Cambridge, MA] and Eli Lilly and Company
      [Indianapolis, IN]; AIR is a registered trademark of Alkermes, Inc.) over insulin
      injection, but the two methods need to be compared for efficacy and safety.
      METHODS: This multicenter, 6-month, parallel-group, noninferiority trial had 500
      patients with type 1 diabetes randomized to morning doses of basal insulin
      glargine plus either preprandial injectable insulin lispro or preprandial AIR
      insulin. We hypothesized that AIR insulin is noninferior (upper bound of the 95%
      confidence interval < or = 0.4%) to insulin lispro for change-from-baseline
      hemoglobin A1C (A1C). RESULTS: Baseline A1C was 7.95 +/- 0.08% for both groups.
      At end point, A1C was lower with insulin lispro than with AIR insulin by 0.27%
      (95% confidence interval 0.11, 0.43; P< 0.001). Noninferiority of AIR insulin to
      insulin lispro was not demonstrated, but similar percentages of patients in each
      group achieved A1C <7.0% (P = 0.448). Overall daily blood glucose was similar
      between groups at baseline (P = 0.879) and end point (P = 0.161). Two-hour
      postprandial blood glucose change from baseline was significantly (P < 0.001)
      higher with AIR insulin (20.77 +/- 4.33 mg/dL at 3 months and 15.85 +/- 3.08
      mg/dL at end point) than with insulin lispro (3.29 +/- 4.14 mg/dL at 3 months and
      1.67 +/- 2.91 mg/dL at end point). Overall hypoglycemia was similar between
      treatment groups (P = 0.355). The AIR insulin group had greater decrease in
      diffusing capacity of the lung for carbon monoxide at end point (P = 0.020) and
      greater incidence of cough (P = 0.024) and dyspnea (P = 0.030). Body weight
      decreased in the AIR insulin group and increased in the insulin lispro group.
      CONCLUSIONS: Insulin lispro provided lower A1C than AIR insulin, but the
      difference may not be clinically relevant.

PMID- 19772446
TI  - Initiation of prandial insulin therapy with AIR inhaled insulin or insulin lispro
      in patients with type 2 diabetes: A randomized noninferiority trial.
AB  - BACKGROUND: Insulin initiation in patients with type 2 diabetes is often delayed
      because of concerns about injections. Our objective was to compare the effects of
      AIR inhaled insulin (Eli Lilly and Co., Indianapolis, IN) (AIR is a registered
      trademark of Alkermes, Inc., Cambridge, MA) with those of injectable insulin on
      glycemic control and safety. METHODS: This was planned as a 24-month, open-label,
      randomized study in adults with diabetes inadequately controlled by one or more
      oral antihyperglycemic medications (OAMs). Following a 2-week baseline period,
      patients continued OAMs and were randomized to AIR insulin (n = 208) or insulin
      lispro (n = 203) before meals. The primary end point was hemoglobin A1C (A1C)
      change from baseline to 6 months. Noninferiority was established if the upper
      limit of the 95% confidence interval of the difference in A1C change was < or
      =0.4%. RESULTS: Early termination of the study diminished the number of patients
      for the 12- and 24-month analyses, but not for the primary 6-month end point
      analyses. AIR insulin and injectable insulin groups had comparable baseline A1C
      values (8.18% vs. 8.21%, respectively). Change in A1C from baseline to 6-month
      end point was similar (least squares mean, -0.81 +/- 0.09% and -0.87 +/- 0.09%;
      95% confidence interval for the difference -0.117, 0.234; P = 0.51) and so were
      final A1C values of 7.36% and 7.31% for AIR insulin and injectable insulin,
      respectively. At 6 months, no differences were observed in eight-point profiles,
      overall and nocturnal hypoglycemia, and weight gain. Greater decreases in
      spirometry were observed in the AIR insulin group at 12 months. Cough was the
      most frequently reported adverse event (20% [AIR insulin] vs. 10% [insulin
      lispro]; P = 0.002). CONCLUSIONS: Treatment with AIR insulin resulted in similar
      improvement in glycemic control compared with insulin lispro. More frequent cough
      and greater decrease in spirometry were observed with AIR insulin.

PMID- 19772447
TI  - Safety and efficacy of AIR inhaled insulin compared with subcutaneous insulin in
      patients having diabetes and asthma: A 12-month, randomized, noninferiority
      trial.
AB  - BACKGROUND: Long-term safety and efficacy of AIR((R)) inhaled insulin (Eli Lilly
      and Co., Indianapolis, IN) (AIR is a registered trademark of Alkermes, Inc.,
      Cambridge, MA) in patients with diabetes and concomitant lung disease remain to
      be established. METHODS: This 1-year, randomized, open-label, active comparator,
      two-arm, parallel study compared the safety and efficacy of AIR insulin to
      subcutaneous (SC) insulin in patients having type 1 or type 2 diabetes and
      asthma. Patients with type 2 diabetes continued taking their prestudy oral
      antihyperglycemic medication. RESULTS: Change in hemoglobin A1C from baseline to
      end point was similar for the AIR insulin and SC insulin groups (-0.063 +/-
      0.128% and -0.315 +/- 0.128% respectively, P = 0.105), but noninferiority failed
      to be achieved (the upper limit of the 95% confidence interval [-0.053, 0.555]
      was >0.4%). The total daily prandial dose increased more in the AIR insulin group
      than in the SC insulin group (0.150 U/kg and 0.044 U/kg, respectively, P =
      0.002). Safety profiles were generally comparable between treatments. At end
      point, forced expiratory volume in 1 s (FEV(1))/forced vital capacity (FVC)
      postbronchodilator (-0.016 +/- 0.005 vs. 0.002 +/- 0.005, P = 0.006) and
      diffusing capacity of the lung for carbon monoxide (-1.214 +/- 0.325 mL/min/torr
      vs. -0.383 +/- 0.311 mL/min/torr, P = 0.028) both decreased more in the AIR
      insulin group than in the SC insulin group, but the differences were not present
      at follow-up. FEV(1) and FVC were similar between treatment groups at end point.
      Incidences of hypoglycemia were comparable between groups. Insulin antibody
      binding increased more in the AIR insulin group. Cough was the most common
      adverse event; however, there was no difference in incidence between the AIR
      insulin (15.3%) and SC insulin (12.4%) treatment groups (P = 0.572). CONCLUSIONS:
      In patients who have diabetes and asthma, AIR insulin demonstrated glycemic
      efficacy similar to SC insulin. Additionally, the safety profile of AIR insulin
      in patients with and without asthma is consistent.

PMID- 19772448
TI  - Does availability of AIR insulin increase insulin use and improve glycemic
      control in patients with type 2 diabetes?
AB  - BACKGROUND: In the concordance model, physician and patient discuss treatment
      options, explore the impact of treatment decisions from the patient's
      perspective, and make treatment choices together. We tested, in a concordance
      setting, whether the availability of AIR inhaled insulin (developed by Alkermes,
      Inc. [Cambridge, MA] and Eli Lilly and Company [Indianapolis, IN]; AIR is a
      registered trademark of Alkermes, Inc.), as compared with existing treatment
      options alone, leads to greater initiation and maintenance of insulin therapy and
      improves glycemic control in patients with type 2 diabetes. METHODS: This was a 9
      month, multicenter, parallel, open-label study in adult, nonsmoking patients with
      diabetes not optimally controlled by two or more oral antihyperglycemic
      medications. Patients were randomized to the Standard Options group (n = 516), in
      which patients chose a regimen from drugs in each major treatment class excluding
      inhaled insulin, or the Standard Options + AIR insulin group (n = 505), in which
      patients had the same choices plus AIR insulin. The primary end points were the
      proportion of patients in each group using insulin at end point and change in
      hemoglobin A1C (A1C) from baseline to end point. RESULTS: At end point, 53% of
      patients in the Standard Options group and 59% in the Standard Options + AIR
      insulin group were using insulin (P = 0.07). Both groups reduced A1C by about
      1.2% and reported increased well-being and treatment satisfaction. The most
      common adverse event with AIR insulin was transient cough. CONCLUSIONS: The
      opportunity to choose AIR insulin did not affect overall use of insulin at end
      point or A1C outcomes. Regardless of group assignment, utilizing a shared
      decision-making approach to treatment choices (concordance model), resulted in
      improved treatment satisfaction and A1C values at end point. Therefore,
      increasing patient involvement in treatment decisions may improve outcomes.

PMID- 19772449
TI  - Two-year efficacy and safety of AIR inhaled insulin in patients with type 1
      diabetes: An open-label randomized controlled trial.
AB  - BACKGROUND: Patients with type 1 diabetes require intensive insulin therapy for
      optimal glycemic control. AIR((R)) inhaled insulin (system from Eli Lilly and
      Company, Indianapolis, IN) (AIR is a registered trademark of Alkermes, Inc.,
      Cambridge, MA) may be an efficacious and safe alternative to subcutaneously
      injected (SC) mealtime insulin. METHODS: This was a Phase 3, 2-year, randomized,
      open-label, active-comparator, parallel-group study in 385 patients with type 1
      diabetes who were randomly assigned to receive AIR insulin or SC insulin (regular
      human insulin or insulin lispro) at mealtimes. Both groups received insulin
      glargine once daily. Efficacy measures included mean change in hemoglobin A1C
      (A1C) from baseline to end point, eight-point self-monitored blood glucose
      profiles, and insulin dosage. Safety assessments included hypoglycemic events,
      pulmonary function tests, adverse events, and insulin antibody levels. RESULTS:
      In both treatment groups, only 20% of subjects reached the target of A1C <7.0%. A
      significant A1C difference of 0.44% was seen favoring SC insulin, with no
      difference between the groups in insulin doses or hypoglycemic events at end
      point. Patients in both treatment groups experienced progressive decreases in
      lung function, but larger (reversible) decrements in diffusing capacity of the
      lung for carbon monoxide (DL(CO)) were associated with AIR insulin treatment.
      Greater weight gain was seen with SC insulin treatment. CONCLUSIONS: The AIR
      inhaled insulin program was terminated by the sponsor prior to availability of
      any Phase 3 data for reasons unrelated to safety or efficacy. Despite early
      termination, this trial provides evidence that AIR insulin was less efficacious
      in lowering A1C and was associated with a greater decrease in DL(CO) and
      increased incidence of cough than SC insulin in patients with type 1 diabetes.

PMID- 19772450
TI  - A comparison between simplified and intensive dose-titration algorithms using AIR
      inhaled insulin for insulin-naive patients with type 2 diabetes in a randomized
      noninferiority trial.
AB  - BACKGROUND: Insulin initiation and optimization is a challenge for patients with
      type 2 diabetes. Our objective was to determine whether safety and efficacy of
      AIR inhaled insulin (Eli Lilly and Co., Indianapolis, IN) (AIR is a registered
      trademark of Alkermes, Inc., Cambridge, MA) using a simplified regimen was
      noninferior to an intensive regimen. METHODS: This was an open-label, randomized
      study in insulin-naive adults not optimally controlled by oral antihyperglycemic
      medications. Simplified titration included a 6 U per meal AIR insulin starting
      dose. Individual doses were adjusted at mealtime in 2-U increments from the
      previous day's four-point self-monitored blood glucose (SMBG) (total < or =6 U).
      Starting Air insulin doses for intensive titration were based on fasting blood
      glucose, gender, height, and weight. Patients conducted four-point SMBG daily for
      the study duration. Insulin doses were titrated based on the previous 3 days'
      mean SMBG (total < or =8 U). RESULTS: End point hemoglobin A1C (A1C) was 7.07 +/-
      0.09% and 6.87 +/- 0.09% for simplified (n = 178) and intensive (n = 180)
      algorithms, respectively. Noninferiority between algorithms was not established.
      The fasting blood glucose (least squares mean +/- standard error) values for the
      simplified (137.27 +/- 3.42 mg/dL) and intensive (133.13 +/- 3.42 mg/dL)
      algorithms were comparable. Safety profiles were comparable. The hypoglycemic
      rate at 4, 8, 12, and 24 weeks was higher in patients receiving intensive
      titration (all P < .0001). The nocturnal hypoglycemic rate for patients receiving
      intensive titration was higher than for those receiving simplified titration at 8
      (P < 0.015) and 12 weeks (P < 0.001). CONCLUSIONS: Noninferiority between the
      algorithms, as measured by A1C, was not demonstrated. This finding re-emphasizes
      the difficulty of identifying optimal, simplified insulin regimens for patients.

PMID- 19772451
TI  - Comparison of prandial AIR inhaled insulin alone to intensified insulin glargine
      alone and to AIR insulin plus intensified insulin glargine in patients with type
      2 diabetes previously treated with once-daily insulin glargine.
AB  - BACKGROUND: Patients with type 2 diabetes often initiate insulin with once-daily
      basal insulin. Over time, many patients intensify their insulin regimens in an
      attempt to attain and sustain glycemic targets. This study compares three
      intensification approaches: changing insulin glargine to preprandial AIR inhaled
      insulin (developed by Alkermes, Inc. [Cambridge, MA] and Eli Lilly and Company
      [Indianapolis, IN]; AIR is a registered trademark of Alkermes, Inc.),
      intensifying glargine via validated titration algorithms (IG), or adding AIR
      insulin while intensifying glargine (AIR + IG). METHODS: Five hundred sixty
      patients with hemoglobin A(1c) (A1C) of 7.5-10.5%, on one or more
      antihyperglycemic medications, and on once-daily insulin glargine for > or =4
      months were randomly allocated to one of the three treatments lasting 52 weeks.
      The primary objective assessed between-group differences in A1C mean change from
      baseline to 24 weeks using last-observation-carried-forward (LOCF) in the intent
      to-treat population. RESULTS: At 24 weeks, A1C was reduced from a mean baseline
      of 8.5% to 7.7%, 7.9%, and 7.5% for the AIR, IG, and AIR + IG groups,
      respectively. AIR produced 0.20% greater A1C decrease than IG (least-squares mean
      difference = -0.20%; 95% confidence interval [CI], -0.39, -0.02). AIR + IG had a
      0.35% greater A1C decrease versus IG (95% CI, -0.57, -0.13). The -0.15%
      difference between AIR + IG versus AIR was not significant (P < 0.198). More
      hypoglycemia categorized as severe occurred with AIR alone versus IG alone at
      LOCF end points. More nocturnal hypoglycemia occurred with IG alone versus AIR
      alone and AIR + IG. CONCLUSIONS: Preprandial inhaled insulin provides an
      alternative for patients not optimized on insulin glargine alone. Glycemic
      control, hypoglycemic risk, delivery preference, and regimen complexity must be
      considered when selecting insulin initiation and optimization regimens.

PMID- 19772452
TI  - AIR insulin capsules of different dose strengths may be combined to yield
      equivalent pharmacokinetics and glucodynamics.
AB  - BACKGROUND: In order to assess pharmacokinetic (PK) and glucodynamic (GD)
      attributes relevant to the end user of an inhaled insulin, this study examined
      the exposure and GD effect of doses of AIR inhaled insulin (Eli Lilly and Co.,
      Indianapolis, IN) (AIR is a registered trademark of Alkermes, Inc., Cambridge,
      MA) by combining capsules of different strengths in healthy subjects. METHODS:
      Fifty-nine healthy, nonsmoking, male or female subjects with normal pulmonary
      function were enrolled in an open-label, randomized, crossover study. Subjects
      underwent up to five euglycemic glucose clamp procedures, separated by 5-18 days.
      The five AIR insulin treatments tested included one 6 unit-equivalent (U-eq)
      capsule containing 2.6 mg of insulin, three 2 U-eq (0.9 mg) capsules (2.7 mg
      total), one 10 U-eq (3.9 mg) capsule, one 6 U-eq capsule plus two 2 U-eq capsules
      (4.4 mg total), and two 10 U-eq capsules (7.8 mg total). Samples for PK and GD
      assessments were taken up to 10 h post-dose. RESULTS: Based on both PK (area
      under the curve from time 0 to time of return to baseline and maximum
      concentration) and GD (total amount of glucose infused and maximum glucose
      infusion rate) responses, administration of a 6 U-eq capsule was equivalent to
      three 2 U-eq capsules; 90% confidence intervals for the ratios were contained
      within the interval (0.8, 1.25). Similarly, both overall exposure and
      glucodynamic response after administration of a 10 U-eq capsule were comparable
      to the 6 U-eq plus two 2 U-eq capsule combination. AIR insulin exhibited PK dose
      proportionality and dose-dependent increases in GD responses over the 2.6-7.8 mg
      dose range. CONCLUSIONS: AIR insulin exhibited dose strength interchangeability
      and dose proportionality after single-dose administration in healthy subjects.

PMID- 19772453
TI  - Billions for biodefense: federal agency biodefense funding, FY2009-FY2010.
AB  - Since 2001, the United States government has spent substantial resources on
      preparing the nation against a bioterrorist attack. Earlier articles in this
      series analyzed civilian biodefense funding by the federal government for fiscal
      years (FY) 2001 through 2009. This article updates those figures with budgeted
      amounts for FY2010, specifically analyzing the budgets and allocations for
      biodefense at the Departments of Health and Human Services, Defense, Homeland
      Security, Agriculture, and State; the Environmental Protection Agency; and the
      National Science Foundation. This year's article also provides an assessment of
      the proportion of the biodefense budget that serves multiple programmatic goals
      and benefits, including research into infectious disease pathogenesis and
      immunology, public health planning and preparedness, and disaster response
      efforts. The FY2010 federal budget for civilian biodefense totals $6.05 billion.
      Of that total, $4.96 billion is budgeted for programs that serve multiple goals
      and provide manifold benefits.

PMID- 19772454
TI  - The effect of insulin-loaded chitosan particle-aggregated scaffolds in
      chondrogenic differentiation.
AB  - Osteochondral defect repair requires a tissue engineering approach that aims at
      mimicking the physiological properties and structure of two different tissues
      (cartilage and bone) using a scaffold-cell construct. One ideal approach would be
      to engineer in vitro a hybrid material using a single-cell source. For that
      purpose, the scaffold should be able to provide the adequate biochemical cues to
      promote the selective but simultaneous differentiation of both tissues. In this
      work, attention was paid primarily to the chondrogenic differentiation by
      focusing on the development of polymeric systems that provide biomolecules
      release to induce chondrogenic differentiation. For that, different formulations
      of insulin-loaded chitosan particle-aggregated scaffolds were developed as a
      potential model system for cartilage and osteochondral tissue engineering
      applications using insulin as a potent bioactive substance known to induce
      chondrogenic differentiation. The insulin encapsulation efficiency was shown to
      be high with values of 70.37 +/- 0.8%, 84.26 +/- 1.76%, and 87.23 +/- 1.58% for
      loadings of 0.05%, 0.5%, and 5%, respectively. The in vitro release profiles were
      assessed in physiological conditions mimicking the cell culture procedures and
      quantified by Micro-BCA protein assay. Different release profiles were obtained
      that showed to be dependent on the initial insulin-loading percentage. Further,
      the effect on prechondrogenic ATDC5 cells was investigated for periods up to 4
      weeks by studying the influence of these release systems on cell morphology, DNA
      and glycosaminoglycan content, histology, and gene expression of collagen types I
      and II, Sox-9, and aggrecan assessed by real-time polymerase chain reaction. When
      compared with control conditions (unloaded scaffolds cultured with the standard
      chondrogenic-inducing medium), insulin-loaded scaffolds upregulated the Sox-9 and
      aggrecan expression after 4 weeks of culture. From the overall results, it is
      reasonable to conclude that the developed loaded scaffolds when seeded with ATDC5
      can provide biochemical cues for chondrogenic differentiation. Among the tested
      formulations, the higher insulin-loaded system (5%) was the most effective in
      promoting chondrogenic differentiation.

PMID- 19772455
TI  - Role of nanofibrous poly(caprolactone) scaffolds in human mesenchymal stem cell
      attachment and spreading for in vitro bone tissue engineering--response to
      osteogenic regulators.
AB  - In this study, we evaluated the role of fiber size scale in the adhesion and
      spreading potential of human mesenchymal stem cells (hMSCs) on electrospun
      poly(caprolactone) (PCL) nanofibrous and microfibrous scaffolds. The effect of in
      vivo regulators in inducing osteogenic differentiation of hMSCs on PCL
      nanofibrous scaffolds was investigated using osteogenic differentiation marker
      gene expression and matrix mineralization. Here, we report for the first time the
      influence of in vivo regulators in an in vitro setting with hMSCs for bone tissue
      engineering on PCL nanofibrous matrices. Our results indicated that hMSCs
      attached and spread rapidly on nanofibrous scaffolds in comparison to
      microfibrous PCL. Further, hMSCs proliferated well on the nanofibrous scaffolds.
      The cells on the nanofibrous PCL were found to differentiate into the osteoblast
      lineage and subsequently mineralize upon addition of in vivo osteogenic
      regulators. The attachment and spreading of hMSCs were more effective on the
      nanofibers compared with the microfibers despite the lower protein surface
      coverage (total adsorbed protein per unit fiber surface area) on nanofibers.

PMID- 19772456
TI  - Osteogenic differentiation influences stem cell migration out of scaffold-free
      microspheres.
AB  - Complete bone regeneration of critical-size defects frequently fail because of
      the use of acellular bone substitutes and because of partially negative
      influences of artificial scaffolds. However, the supply of cells to critical-size
      defects is essential for the regeneration. Therefore, engineered scaffold-free
      tissues, with outgrowing cells that fill up spaces in the bony defect, are
      promising candidates for bone regeneration approaches. Here, we demonstrate such
      a scaffold-free tissue construct (microspheres) that, if osteogenic
      differentiated, mineralizes while maintaining the capability to let cells grow
      out of the united cell structure. A superior outgrowth capability of microspheres
      composed of human cord blood-derived unrestricted somatic stem cells compared
      with murine embryonic stem cells was found and a time-dependent reduction in
      outgrowth was evident in vitro. Even after 5 days of osteoinduction and strong
      mineralization, the cells migrate out of the microsphere. As migration of cells
      out of unrestricted somatic stem cell microspheres was also found in
      extracellular matrix gel, we suggest that cells would migrate also in vivo. Thus,
      microspheres could serve as the scaffold and the source of osteogenic cells in
      future bone regeneration approaches. Further, microspheres permit the precise
      administration of large amount of cells into an area of interest.

PMID- 19772457
TI  - Stem cell-related gene expression in clonal populations of mesenchymal stromal
      cells from bone marrow.
AB  - Decline in the frequency of potent mesenchymal stem cells (MSCs) has been
      implicated in ageing and degenerative diseases. Increasing the circulating stem
      cell population can lead to renewed recruitment of these potent cells at sites of
      damage. Therefore, identifying the ideal cells for ex vivo expansion will form a
      major pursuit of clinical applications. This study is a follow-up of previous
      work that demonstrated the occurrence of fast-growing multipotential cells from
      the bone marrow samples. To investigate the molecular processes involved in the
      existence of such varying populations, gene expression studies were performed
      between fast- and slow-growing clonal populations to identify potential genetic
      markers associated with stemness using the quantitative real-time polymerase
      chain reaction comprising a series of 84 genes related to stem cell pathways. A
      group of 10 genes were commonly overrepresented in the fast-growing stem cell
      clones. These included genes that encode proteins involved in the maintenance of
      embryonic and neural stem cell renewal (sex-determining region Y-box 2, notch
      homolog 1, and delta-like 3), proteins associated with chondrogenesis (aggrecan
      and collagen 2 A1), growth factors (bone morphogenetic protein 2 and insulin-like
      growth factor 1), an endodermal organogenesis protein (forkhead box a2), and
      proteins associated with cell-fate specification (fibroblast growth factor 2 and
      cell division cycle 2). Expression of diverse differentiation genes in MSC clones
      suggests that these commonly expressed genes may confer the maintenance of
      multipotentiality and self-renewal of MSCs.

PMID- 19772458
TI  - The functional and neuroprotective actions of Neu2000, a dual-acting
      pharmacological agent, in the treatment of acute spinal cord injury.
AB  - The goal of the present study was to examine the neuroprotective and functional
      significance of targeting both N-methyl-D-aspartate (NMDA) receptor-mediated
      excitotoxicity and oxidative stress using a dual-acting compound, Neu2000, in rat
      model of moderate spinal cord injury (SCI). An initial set of experiments was
      conducted in uninjured rats to study the pharmacokinetic profile of Neu2000
      following intraperitoneal and intravenous administration. A second experiment
      measured free radical production in mitochondria isolated from sham or injured
      spinal cords of animals receiving vehicle or Neu2000 treatment. A third set of
      animals was divided into three treatment groups consisting of vehicle treatment,
      a single dose of Neu2000 (50 mg/kg) administered at 10 min following injury, or a
      repeated treatment paradigm consisting of a single bolus of Neu2000 at 10 min
      following injury (50 mg/kg) plus a maintenance dose (25 mg/kg) administered every
      24 h for an additional 6 days. Animals were tested once a week for a period of 6
      weeks for evidence of locomotor recovery in an open field and kinematic analysis
      of fine motor control using the DigiGait Image Analysis System. At the end of the
      testing period, spinal cord reconstruction was performed to obtain nonbiased
      stereological measures of tissue sparing. The results of this study demonstrate
      that Neu2000 treatment significantly reduced the production of mitochondrial free
      radicals and improved locomotor outcomes that were associated with a significant
      increase in the volume of spared spinal cord tissue.

PMID- 19772460
TI  - Cardiometabolic risk factors in experimental spinal cord injury.
AB  - Cardiometabolic risk factors are sorely underreported after spinal cord injury
      (SCI), despite the high prevalence of metabolic disorders and cardiovascular
      mortality in this population. Body-composition analysis and serum-lipid profiling
      are two assessments that are beginning to be more widely used to document
      metabolic changes after clinical SCI. Individuals with SCI have been reported to
      carry increased visceral fat and to exhibit altered serum-lipid levels. However,
      little is known about the development of these cardiometabolic risk factors in
      animal models. Using a combination of magnetic resonance imaging (MRI) and
      adipose tissue dissection, we show that visceral and subcutaneous adipose tissue
      were both increased at 1 month, but not at 1 week, after complete T3 SCI in rats.
      Additionally, at 1 month post injury, T3 SCI rats exhibited nonfasting serum
      hypertriglyceridemia, a result obtained using both standard clinical methods and
      a home cholesterol monitoring device (CardioChek). Interestingly, at 1 month post
      injury, rats with complete T10 SCI did not show an increase in either visceral
      adiposity or serum triglyceride levels. The fact that complete high-thoracic SCI
      disrupts lipid metabolism and perturbs fat storage in the subacute period, while
      low-thoracic SCI does not, suggests that differences in descending sympathetic
      control of adipose tissue might play a role in these changes. These results
      provide the first evidence of cardiometabolic risk factors in experimental
      animals with SCI, and are a starting point for investigations of the etiology of
      obesity and metabolic dysfunctions that often accompany SCI.

PMID- 19772459
TI  - Simulated whiplash modulates expression of the glutamatergic system in the spinal
      cord suggesting spinal plasticity is associated with painful dynamic cervical
      facet loading.
AB  - The cervical facet joint and its capsule have been reported to be injured during
      whiplash scenarios and are a common source of chronic neck pain from whiplash.
      Both the metabotropic glutamate receptor 5 (mGluR5) and the excitatory amino acid
      carrier 1 (EAAC1) have pivotal roles in chronic pain. In this study, spinal
      mGluR5 and EAAC1 were quantified following painful facet joint distraction in a
      rat model of facet-mediated painful loading and were evaluated for their
      correlation with the severity of capsule loading. Rats underwent either a dynamic
      C6/C7 joint distraction simulating loading experienced during whiplash
      (distraction; n = 12) or no distraction (sham; n = 6) to serve as control. The
      severity of capsular loading was quantified using strain metrics, and mechanical
      allodynia was assessed after surgery. Spinal cord tissue was harvested at day 7
      and the expression of mGluR5 and EAAC1 were quantified using Western blot
      analysis. Mechanical allodynia following distraction was significantly (p <
      0.001) higher than sham. Spinal expression of mGluR5 was also significantly (p <
      0.05) greater following distraction relative to sham. However, spinal EAAC1 was
      significantly (p = 0.0003) reduced compared to sham. Further, spinal mGluR5
      expression was significantly positively correlated to capsule strain (p < 0.02)
      and mechanical allodynia (p < 0.02). Spinal EAAC1 expression was significantly
      negatively related to one of the strain metrics (p < 0.003) and mechanical
      allodynia at day 7 (p = 0.03). These results suggest that the spinal
      glutamatergic system may potentiate the persistent behavioral hypersensitivity
      that is produced following dynamic whiplash-like joint loading; chronic whiplash
      pain may be alleviated by blocking mGluR5 expression and/or enhancing glutamate
      transport through the neuronal transporter EAAC1.

PMID- 19772461
TI  - Recognition of O6MeG lesions by MGMT and mismatch repair proficiency may be a
      prerequisite for low-dose radiation hypersensitivity.
AB  - Low-dose hyper-radiosensitivity (HRS) is the phenomenon whereby cells exposed to
      radiation doses of less than approximately 0.5 Gy exhibit increased cell killing
      relative to that predicted from back-extrapolating high-dose survival data using
      a linear-quadratic model. While the exact mechanism remains to be elucidated, the
      involvement of several molecular repair pathways has been documented. These
      processes in turn are also associated with the response of cells to O6
      methylguanine (O6MeG) lesions. We propose a model in which the level of low-dose
      cell killing is determined by the efficiency of both pre-replicative repair by
      the DNA repair enzyme O6-methylguanine methyltransferase (MGMT) and post
      replicative repair by the DNA mismatch repair (MMR) system. We therefore
      hypothesized that the response of cells to low doses of radiation is dependent on
      the expression status of MGMT and MMR proteins. MMR (MSH2, MSH6, MLH1, PMS1,
      PMS2) and MGMT protein expression signatures were determined in a panel of normal
      (PWR1E, RWPE1) and malignant (22RV1, DU145, PC3) prostate cell lines and
      correlated with clonogenic survival and cell cycle analysis. PC3 and RWPE1 cells
      (HRS positive) were associated with MGMT and MMR proficiency, whereas HRS
      negative cell lines lacked expression of at least one (MGMT or MMR) protein. MGMT
      inactivation had no significant effect on cell survival. These results indicate a
      possible role for MMR-dependent processing of damage produced by low doses of
      radiation.

PMID- 19772463
TI  - High content analysis of human fibroblast cell cultures after exposure to space
      radiation.
AB  - Space travel imposes risks to human health, in large part by the increased
      radiation levels compared to those on Earth. To understand the effects of space
      radiation on humans, it is important to determine the underlying cellular
      mechanisms. While general dosimetry describes average radiation levels
      accurately, it says little about the actual physiological impact and does not
      provide biological information about individual cellular events. In addition,
      there is no information about the nature and magnitude of a systemic response
      through extra- and intercellular communication. To assess the stress response in
      human fibroblasts that were sent into space with the Foton-M3 mission, we have
      developed a pluralistic setup to measure DNA damage and inflammation response by
      combining global and local dosimetry, image cytometry and multiplex array
      technology, thereby maximizing the scientific output. We were able to demonstrate
      a significant increase in DNA double-strand breaks, determined by a twofold
      increase of the gamma-H2AX signal at the level of the single cell and a threefold
      up-regulation of the soluble signal proteins CCL5, IL-6, IL-8, beta-2
      microglobulin and EN-RAGE, which are key players in the process of inflammation,
      in the growth medium.

PMID- 19772462
TI  - Synthetic protection short interfering RNA screen reveals glyburide as a novel
      radioprotector.
AB  - To assist in screening existing drugs for use as potential radioprotectors, we
      used a human unbiased 16,560 short interfering RNA (siRNA) library targeting the
      druggable genome. We performed a synthetic protection screen that was designed to
      identify genes that, when silenced, protected human glioblastoma T98G cells from
      gamma-radiation-induced cell death. We identified 116 candidate protective genes,
      then identified 10 small molecule inhibitors of 13 of these candidate gene
      products and tested their radioprotective effects. Glyburide, a clinically used
      second-generation hypoglycemic drug, effectively decreased radiation-induced cell
      death in several cell lines including T98G, glioblastoma U-87 MG, and normal lung
      epithelial BEAS-2B and in primary cultures of astrocytes. Glyburide significantly
      increased the survival of 32D cl3 murine hematopoietic progenitor cells when
      administrated before irradiation. Glyburide was radioprotective in vivo (90% of
      C57BL/6NHsd female mice pretreated with 10 mg/kg glyburide survived 9.5 Gy total
      body irradiation compared to 42% of irradiated controls, P = 0.0249). These
      results demonstrate the power of unbiased siRNA synthetic protection screening
      with a druggable genome library to identify new radioprotectors.

PMID- 19772465
TI  - Reversible effect of magnetic fields on human lymphocyte activation patterns:
      different sensitivity of naive and memory lymphocyte subsets.
AB  - The aim of this study was to investigate the influence of 50 Hz magnetic or
      static magnetic fields of 0.5 mT on subsets of human CD4(+) T cells in terms of
      cytokine release/content, cell proliferation and intracellular free calcium
      concentration. CD4(+) T cells can be divided into different subsets on the basis
      of surface marker expression, such as CD45, and T cells can be divided into naive
      (CD45RA(+)) and memory (CD45RA(-)) cells. In this study, the effects of magnetic
      fields after 24 and 48 h of cell culture were analyzed. We found that the
      CD4(+)CD45RA(-) T subset were more sensitive after 2 h of exposure. Decreases in
      the release/content of IFN-gamma, in cell proliferation and in intracellular free
      calcium concentrations were observed in exposed CD4(+)CD45RA(-) T cells compared
      to CD4(+)CD45RA(+) T cells. The results suggest that exposure to the magnetic
      fields induces a delay in the response to stimulants and that modifications are
      rapidly reversible, at least after a short exposure.

PMID- 19772464
TI  - Induction of cytokine gene expression in human thyroid epithelial cells
      irradiated with HZE particles (iron ions).
AB  - Gene expression profiles were examined using cDNA microarray technology in human
      thyroid epithelial (Htori-3) cells exposed to a low, non-toxic dose (10 cGy) of
      radiation from HZE particles in the form of iron ions in the absence or presence
      of selenomethionine (SeM). A total of 215 genes were differentially regulated 2 h
      after exposure to a 10-cGy dose of iron-ion radiation. In the microarray
      analysis, SeM had profound effects on the radiation-induced expression of several
      specific genes, which includes PLAU, IGFBP3, FOLR1, B4GALT1 and COL1A1. Of
      particular interest to us was a gene cluster, "secreted proteins", that was up
      regulated after radiation exposure. Seven up-regulated genes of this gene cluster
      fall within the chemokine/cytokine gene cluster, namely, CXCL1, CXCL2, IL6, IL11,
      IL8, IL24 and TGFbeta2. In microarray studies, the radiation-induced up-regulated
      expression of some these genes encoding cytokine/chemokine proteins was
      significantly decreased by SeM treatment. For IL8, TGFbeta2, CXCL1 and CXCL2,
      these observations were validated by qPCR techniques. It is concluded that SeM
      can regulate ionizing radiation-induced gene expression and may serve as an
      effective countermeasure for some of the acute inflammatory/immune responses
      induced by low-dose HZE-particle radiation.

PMID- 19772466
TI  - Photodynamic treatment of culture medium containing serum induces long-lasting
      toxicity in vitro.
AB  - Photodynamic therapy (PDT) produces singlet oxygen and reactive oxygen species
      (ROS) that damage tumor cells and the vasculature. The resulting effect is a
      balance between photo-oxidations through primary or secondary ROS and scavenging
      activity. Sensitizers are distributed in the extracellular space before and
      during cell sensitization, suggesting that PDT could act directly on cell
      structures and on extracellular compartments, including sera. In this study we
      endeavored to determine whether the application of PDT to culture medium could
      affect cell survival. Culture medium [RPMI 1640 supplemented with fetal calf
      serum (FCS)] was incubated with Rose Bengal and irradiated before being added to
      cells for various contact times as a replacement for untreated medium. Cells were
      then kept in darkness until the survival assay. Treated medium reduced cell
      survival by up to 40% after 30 min of contact for 10 microg/ml of Rose Bengal and
      20 J/cm(2). Rose Bengal or m-THPC alone or irradiated in water had no effect.
      This effect was dependent on the doses of Rose Bengal and light and decreased
      when FCS was replaced by human serum mixed with FCS. The reduction in survival
      observed with treated medium was more pronounced when the cell doubling time was
      shorter. Analysis of ROS or peroxide production in treated medium by DCFH added
      at the end of irradiation of Rose Bengal in serum-containing medium revealed a
      long-lasting oxidizing activity. Our findings support the hypothesis of an ROS-
      or peroxide-mediated, PDT-induced, long-lasting cell toxicity.

PMID- 19772467
TI  - Chk2 protects against radiation-induced genomic instability.
AB  - The murine Chk2 kinase is activated after exposure to ionizing radiation and is
      necessary for p53-dependent apoptosis, but the role Chk2 plays in determining
      genomic stability is poorly understood. By analyzing the sensitivity of Chk2
      deficient murine and human cells to a range of DNA-damaging agents, we show that
      Chk2 deficiency results in resistance to agents that generate double-strand
      breaks but not to other forms of damage. Surprisingly, the absence of Chk2
      results in increased sensitivity to UV-radiation-induced DNA damage. Defective
      apoptosis after radiation-induced DNA damage may result in genomic instability;
      therefore, the consequences of Chk2 deficiency on genomic instability were
      assayed using an in vitro screen. Gene amplification was not detected in
      untreated Chk2(-/-) cells, but the rate of gene amplification after irradiation
      was elevated and was similar to that found in p53 compromised cells. A
      synergistic increase in genomic instability was seen after disruption of both
      Chk2 and p53 function, indicating that the two proteins have non-redundant roles
      in regulating genome stability after irradiation. The data demonstrate that Chk2
      functions to maintain genome integrity after radiation-induced damage and has
      important implications for the use of Chk2 inhibitors as adjuvant cancer therapy.

PMID- 19772468
TI  - Biological effects of high-energy neutrons measured in vivo using a vertebrate
      model.
AB  - Interaction of solar protons and galactic cosmic radiation with the atmosphere
      and other materials produces high-energy secondary neutrons from below 1 to 1000
      MeV and higher. Although secondary neutrons may provide an appreciable component
      of the radiation dose equivalent received by space and high-altitude air
      travelers, the biological effects remain poorly defined, particularly in vivo in
      intact organisms. Here we describe the acute response of Japanese medaka (Oryzias
      latipes) embryos to a beam of high-energy spallation neutrons that mimics the
      energy spectrum of secondary neutrons encountered aboard spacecraft and high
      altitude aircraft. To determine RBE, embryos were exposed to 0-0.5 Gy of high
      energy neutron radiation or 0-15 Gy of reference gamma radiation. The radiation
      response was measured by imaging apoptotic cells in situ in defined volumes of
      the embryo, an assay that provides a quantifiable, linear dose response. The
      slope of the dose response in the developing head, relative to reference gamma
      radiation, indicates an RBE of 24.9 (95% CI 13.6-40.7). A higher RBE of 48.1 (95%
      CI 30.0-66.4) was obtained based on overall survival. A separate analysis of
      apoptosis in muscle showed an overall nonlinear response, with the greatest
      effects at doses of less than 0.3 Gy. Results of this experiment indicate that
      medaka are a useful model for investigating biological damage associated with
      high-energy neutron exposure.

PMID- 19772470
TI  - Biodistribution of (10)B for Boron Neutron Capture Therapy (BNCT) in a mouse
      model after injection of sodium mercaptoundecahydro-closo-dodecaborate and l-para
      boronophenylalanine.
AB  - In boron neutron capture therapy, the absorbed dose from the (10)B(n,alpha)(7)Li
      reaction depends on the (10)B concentration and (10)B distribution in the
      irradiated volume. Thus compounds used in BNCT should have tumor-specific uptake
      and low accumulation in normal tissues. This study compares in a mouse model the
      (10)B uptake in different organs as delivered by l-para-boronophenylalanine (BPA,
      700 mg/kg body weight, i.p.) and/or sodium mercaptoundecahydro-closo-dodecaborate
      (BSH, 200 mg/kg body weight, i.p). After BSH injection, the (10)B concentration
      was high in kidneys (20 +/- 12 microg/g) and liver (20 +/- 12 microg/g) but was
      low in brain (1.0 +/- 0.8 microg/g) and muscle (1.9 +/- 1.2 microg/g). After BPA
      injection, the (10)B concentration was high in kidneys (38 +/- 25 microg/g) and
      spleen (17 +/- 8 microg/g) but low in brain (5 +/- 3 microg/g). After combined
      BPA and BSH injection, the effect on the absolute (10)B concentration was
      additive in all organs. The ratio of the (10)B concentrations in tissues and
      blood differed significantly for the two compounds depending on the compound
      combination, which implies a different uptake profile for normal organs.

PMID- 19772469
TI  - Deoxyribonuclease I is essential for DNA fragmentation induced by gamma radiation
      in mice.
AB  - Gamma radiation is known to induce cell death in several organs. This damage is
      associated with endonuclease-mediated DNA fragmentation; however, the enzyme that
      produces the latter and is likely to cause cell death is unknown. To determine
      whether the most abundant cytotoxic endonuclease DNase I mediates gamma-radiation
      induced tissue injury, we used DNase I knockout mice and zinc chelate of 3,5
      diisopropylsalicylic acid (Zn-DIPS), which, as we show, has DNase I inhibiting
      activity in vitro. The study demonstrated for the first time that inactivation or
      inhibition of DNase I ameliorates radiation injury to the white pulp of spleen,
      intestine villi and bone marrow as measured using a quantitative TUNEL assay. The
      spleen and intestine of DNase I knockout mice were additionally protected from
      radiation by Zn-DIPS, perhaps due to the broad radioprotective effect of the zinc
      ions. Surprisingly, the main DNase I-producing tissues such as the salivary
      glands, pancreas and kidney showed no effect of DNase I inactivation. Another
      unexpected observation was that even without irradiation, DNA fragmentation and
      cell death were significantly lower in the intestine of DNase I knockout mice
      than in wild-type mice. This points to the physiological role of DNase I in
      normal cell death in the intestinal epithelium. In conclusion, our results
      suggested that DNase I-mediated mechanism of DNA damage and subsequent tissue
      injury are essential in gamma-radiation-induced cell death in radiosensitive
      organs.

PMID- 19772471
TI  - Gene expression changes in medical workers exposed to radiation.
AB  - The use of nuclear resources for medical purposes causes considerable concern
      about occupational exposure. Nevertheless, little information is available
      regarding the effects of low-dose irradiations protracted over time. We used
      oligomicroarrays to identify the genes that are transcriptionally regulated by
      persistent exposure to extremely low doses of ionizing radiation in 28 exposed
      professionals (mean cumulative effective dose +/- SD, 19 +/- 38 mSv) compared
      with a matched sample of nonexposed subjects. We identified 256 modulated genes
      from peripheral blood mononuclear cells profiles, and the main biological
      processes we found were DNA packaging and mitochondrial electron transport NADH
      to ubiquinone. Next we investigated whether a different pattern existed when only
      22 exposed subjects with accumulated doses >2.5 mSv, a threshold corresponding to
      the natural background radiation in Italy per year, and mean equal to 25 +/- 41
      mSv were used. In addition to DNA packaging and NADH dehydrogenase function, the
      analysis of the higher-exposed subgroup revealed a significant modulation of ion
      homeostasis and programmed cell death as well. The changes in gene expression
      that we found suggest different mechanisms from those involved in high-dose
      studies that may help to define new biomarkers of radiation exposure for
      accumulated doses below 25 mSv.

PMID- 19772472
TI  - Radiation risk modeling of thyroid cancer with special emphasis on the Chernobyl
      epidemiological data.
AB  - Two recent studies analyzed thyroid cancer incidence in Belarus and Ukraine
      during the period from 1990 to 2001, for the birth cohort 1968 to 1985, and the
      related (131)I exposure associated with the Chernobyl accident in 1986.
      Contradictory age-at-exposure and time-since-exposure effect modifications of the
      excess relative risk (ERR) were reported. The present study identifies the choice
      of baseline modeling method as the reason for the conflicting results. Various
      quality-of-fit criteria favor a parametric baseline model to various categorical
      baseline models. The model with a parametric baseline results in a decrease of
      the ERR by a factor of about 0.2 from an age at exposure of 5 years to an age at
      exposure of 15 years (for a time since exposure of 12 years) and a decrease of
      the ERR from a time since exposure of 4 years to a time since exposure of 14
      years of about 0.25 (for an age at exposure of 10 years). Central ERR estimates
      (of about 20 at 1 Gy for an age at exposure of 10 years and an attained age of 20
      years) and their ratios for females compared to males (about 0.3) turn out to be
      relatively independent of the modeling. Excess absolute risk estimates are also
      predicted to be very similar from the different models. Risk models with
      parametric and categorical baselines were also applied to thyroid cancer
      incidence among the atomic bomb survivors. For young ages at exposure, the ERR
      values in the model with a parametric baseline are larger. Both data sets cover
      the period of 12 to 15 years since exposure. For this period, higher ERR values
      and a stronger age-at-exposure modification are found for the Chernobyl data set.
      Based on the results of the study, it is recommended to test parametric and
      categorical baseline models in risk analyses.

PMID- 19772474
TI  - The age at which cancer occurs-an overlooked parameter!

PMID- 19772473
TI  - Modification of mortality and tumorigenesis by tocopherol-mono-glucoside (TMG)
      administered after X irradiation in mice and rats.
AB  - The effects of TMG [2-(alpha-d-glucopyranosyl) methyl-2,5,7,8-tetramethylchroman
      6-ol], a water-soluble vitamin E derivative, administered after irradiation on
      the mortality of X-irradiated mice and on the development of tumors in the
      mammary and pituitary glands in rats were investigated. When TMG (650 mg/kg) was
      administered intraperitoneally (i.p.) to C3H mice immediately after whole-body
      exposure to 7 Gy radiation, the 30-day survival was significantly higher than
      that of the control mice. The i.p. administration of TMG at 4 h after irradiation
      significantly improved survival compared to that of the controls, but
      administration 8 h after irradiation did not have a significant effect.
      Subcutaneous administration of TMG immediately after irradiation also decreased
      mortality significantly. When dams of lactating Wister rats were exposed to 1.5
      Gy of X rays at day 21 after parturition and were then treated with
      diethylstilbestrol as a tumor promoter, the incidence of mammary tumors and
      pituitary tumors was increased compared to that in the nonirradiated control
      group. The administration of TMG (600 mg/kg, i.p.) after irradiation
      significantly reduced the incidence of mammary tumors and pituitary tumors. The
      number of rats that were free of both mammary and pituitary gland tumors was
      enhanced fourfold by TMG. These results suggest that TMG is effective in
      preventing radiation-induced bone marrow death in mice and in reducing mammary
      and pituitary tumors in rats even when it is administered after irradiation.

PMID- 19772475
TI  - Patricia W. Durbin (1927-2009).

PMID- 19772477
TI  - Cortisol dynamics in the acute phase of aneurysmal subarachnoid hemorrhage:
      associations with disease severity and outcome.
AB  - The purpose of this study was to assess cortisol dynamics in the acute phase
      after aneurysmal subarachnoid hemorrhage (SAH) and to set the parameters of
      cortisol release in relation to the severity of illness and outcome. In 22
      consecutive patients with aneurysmal SAH, cortisol, corticosteroid binding
      globulin, interleukin-6, and adrenocorticotrophic hormone were measured
      immediately after hospital admission (t(0)), 7 days (t(1)) later, and at least 14
      days later (t(2)). Additionally, diurnal profiles of cortisol secretion were
      assessed at t(1) and t(2), and area under the curve (AUC) was computed for
      calculated free serum cortisol (CFSC). In this study, normal diurnal CFSC
      profiles were associated with a significantly shorter ICU-stay, less
      complications, and a more favorable outcome than abnormal diurnal profiles. AUC
      and 8 a.m. cortisol were not related to clinical course or outcome. It is
      concluded that cortisol secretion patterns are associated with the severity and
      outcome of SAH. For an appraisal of the hypothalamo-pituitary-adrenal axis in SAH
      patients, single cortisol measurements are insufficient.

PMID- 19772476
TI  - Neuroprotective effects of selective N-type VGCC blockade on stretch-injury
      induced calcium dynamics in cortical neurons.
AB  - Acute elevation in intracellular calcium ([Ca(2+)](i)) following traumatic brain
      injury (TBI) can trigger cellular mechanisms leading to neuronal dysfunction and
      death. The mechanisms underlying these processes are not completely understood,
      but calcium influx through N-type voltage-gated calcium channels (VGCCs) appears
      to play a central role. The present study examined the time course of [Ca(2+)](i)
      flux, glutamate release, and loss of cell viability following injury using an in
      vitro neuronal-glial cortical cell-culture model of TBI. The effects of N-channel
      blockade with SNX-185 (e.g. omega-conotoxin TVIA) before or after injury were
      also examined. Neuronal injury produced a transient elevation in [Ca(2+)](i),
      increased glutamate release, and resulted in neuronal and glial death. SNX-185
      administered before or immediately after cell injury reduced glutamate release
      and increased the survival of neurons and astrocytes, whereas delayed treatment
      did not improve cell survival but significantly facilitated the return of
      [Ca(2+)](i) to baseline levels. The new findings that N-type VGCCs are critically
      involved in injury-induced glutamate release and recovery of [Ca(2+)](i) argue
      for continued investigation of this treatment strategy for the clinical
      management of TBI. In particular, SNX-185 may represent an effective class of
      drugs that can significantly protect injured neurons from the secondary insults
      that commonly occur after TBI.

PMID- 19772478
TI  - Quantitative magnetic resonance imaging assessment of matrix development in cell
      seeded natural urinary bladder smooth muscle tissue-engineered constructs.
AB  - The approach of cell-seeded natural scaffolds holds great promise for tissue
      engineering complicated soft-tissue organs such as the urinary bladder and heart.
      However, relatively little is known about cell-natural scaffold interactions or
      their influence on magnetic resonance imaging (MRI) characterization, which is
      valuable for noninvasive monitoring. Ideally, MRI should provide information on
      tissue biochemistry in addition to structure and function. In this study,
      quantitative MRI was performed on control and smooth muscle cell-seeded natural
      bladder matrices at different time points up to 7 days postseeding. Measurements
      of MR relaxation times (T1 and T2) and diffusion coefficient (D) showed an
      overall change that was incompatible with cell presence. Multicomponent T2
      provided greater specificity, revealing time-course changes in the short T2
      fraction that were consistent with biochemically determined matrix degradation
      from collagenase released from seeded cells. These matrix alterations are noted
      for the first time, and their relatively early occurrence may be unique to soft
      tissue matrices compared with synthetic materials. More importantly, they are not
      evident on histology but are revealed on quantitative MRI. We conclude that
      quantitative MRI may provide specific information on cell-matrix interaction and
      is a promising noninvasive approach to understand and monitor cell-seeded natural
      scaffold-based regeneration.

PMID- 19772479
TI  - Associations of urban air particulate composition with inflammatory and cytotoxic
      responses in RAW 246.7 cell line.
AB  - Epidemiological studies show heterogeneities in the particulate pollution-related
      exposure-effect relationships among cardiorespiratory patients, but the
      connection to chemical composition and toxic properties of the inhaled particles
      is largely unknown. To identify the chemical constituents and sources responsible
      for the diverse inflammatory and cytotoxic effects of urban air, fine (PM(2.5
      0.2)) and coarse (PM(10-2.5)) particulate samples were collected during
      contrasting air pollution situations. We exposed mouse RAW 246.7 macrophages for
      24 hrs to PM(2.5-0.2) and PM(10-2.5) samples from six European cities. The
      concentrations of proinflammatory cytokines (IL-6, TNFalpha), chemokine (MIP-2),
      and nitric oxide were measured from the cell culture medium, and the cytotoxicity
      was assayed. Spearman's correlations between the chemical constituents and
      cellular responses were analyzed. In the PM(2.5-0.2) size range, the tracers of
      photo-oxidation of organics in the atmosphere (oxalate, succinate, malonate),
      some transition metals (Ni, V, Fe, Cu, Cr), and insoluble soil constituents (Ca,
      Al, Fe, Si) correlated positively with the response parameters. In contrast, the
      tracers of incomplete biomass (monosaccharide anhydrides) and coal (As)
      combustion, and polycyclic aromatic hydrocarbons (PAHs), had negative
      correlations with the inflammatory activity. The compositions of PM(10-2.5)
      samples were more uniform and there were only occasional high correlations
      between the chemical constituents, endotoxin, and the response parameters. The
      present results suggest that the local sources of incomplete combustion and
      resuspended road dust are important producers of harmful fine particulate
      constituents that may, however, operate via diverse toxicity mechanisms. The
      results agree well with our recent findings in the mouse lung.

PMID- 19772480
TI  - Methylhexahydrophthalic anhydride adducted albumin tryptic peptides in nasal
      lavage fluid.
AB  - Methylhexahydrophthalic anhydride (MHHPA) is a reactive, low molecular weight
      chemical used in products such as plastics, paints, and electronic components.
      Exposure to MHHPA may lead to work-related airway diseases such as rhinitis,
      conjunctivitis, and asthma. Twelve subjects employed at a plant manufacturing
      electrical capacitors using MHHPA were included in this study. Nasal lavages were
      collected from subjects before work Monday morning and after work Tuesday
      afternoon. The levels of MHHPA adducted to serum albumin were analyzed with a
      straightforward work-up method. The samples were trypsinated before being
      analyzed with a liquid chromatography-triple quadrupole mass spectrometer. The
      mass spectrometer was run using selected reaction monitoring for six adducted
      peptides. Also, some biomarkers of effect (albumin, total protein, eosinophil
      cationic protein, and tryptase) were analyzed in nasal lavages. Furthermore, the
      metabolite MHHP acid in urine after work on Tuesday was analyzed by gas
      chromatography-mass spectrometry. Symptoms from the airways and the eyes and
      sensitization were registered. The main result of this study is that protein
      adducts can be analyzed in vivo after low occupational exposures to MHHPA. The
      results also show a correlation between adducted peptides and albumin in nasal
      lavage. Furthermore, there may be a difference in the potential to induce
      hyperresponsiveness between adducts bound to different amino acids.

PMID- 19772481
TI  - Simulation and minimisation of the airway deposition of airborne bacteria.
AB  - Respiratory infections represent one of the most important bioaerosol-associated
      health effects. Bacteria are infectious micro-organisms that may, after
      inhalation, cause specific respiratory diseases. Although a large number of
      inhalable pathogenic bacteria have been identified and the related respiratory
      symptoms are well known, their airway transport and deposition are still not
      fully explored. The objective of this work was to characterise the deposition of
      inhaled bacteria in different regions of the lung and to find the optimum
      breathing modes, which ensure the minimum chance of a bacterial infection in a
      given environment. For this purpose a stochastic computer lung model has been
      applied. In order to find the breathing pattern that yields the lowest deposited
      fraction of the inhaled particles, multiple simulations were carried out with
      several combinations of tidal volumes ranging from 400 to 2000 ml, and breathing
      cycles ranging from 2 to 10 s. Particle aerodynamic diameters varied between 1
      and 20 mum, and simulations were performed for both nose and mouth breathing
      conditions. Present computations demonstrated that regional (extrathoracic,
      tracheobronchial, acinar), lobar, and generation number-specific deposition
      distributions of the inhaled particles are highly sensitive to their aerodynamic
      diameter and to the breathing parameters. According to our results, mouth
      breathing with short breathing periods, no breath hold, and low tidal volumes
      minimises the total respiratory system deposition. On the other hand, lung
      (bronchial and acinar) deposition can be minimised by a breathing mode
      characterised by short breathing cycles through the nose with long breath holds
      after exhalations and high tidal volumes.

PMID- 19772482
TI  - Expression of cytokine-induced neutrophil chemoattractant in rat lungs by
      intratracheal instillation of nickel oxide nanoparticles.
AB  - Since nanoparticles easily agglomerate to form larger particles, it is important
      to maintain the size of their agglomerates at the nano-level to evaluate the
      harmful effect of the nanoparticles. We prevented agglomeration of nickel oxide
      nanoparticles by ultrasound diffusion and filtration, established an acute
      exposure model using animals, and examined inflammation and chemokine expression.
      The mass median diameter of nickel oxide nanoparticle agglomerates suspended in
      distilled water for intratracheal instillation was 26 nm (8.41 nm weighted
      average surface primary diameter). Male Wistar rats received intratracheal
      instillation of nickel oxide nanoparticles at 0.1 mg (0.33 mg/kg) or 0.2 mg (0.66
      mg/kg), and were dissected 3 days, 1 week, 1 month, 3 months, and 6 months after
      the instillation. The control group received intratracheal instillation of
      distilled water. Three chemokines (cytokine-induced neutrophil chemoattractant-1
      (CINC-1), CINC-2alphabeta, and CINC-3) in the lung tissue and bronchoalveolar
      lavage fluid (BALF) were determined by quantitative measurement of protein by
      ELISA. Both CINC-1 and CINC-2alphabeta concentration was elevated from day 3 to 3
      months in lung tissue and from day 3 to 6 months in BALF. On the other hand, CINC
      3 was elevated on day 3 in both lung tissue and BALF, and then decreased. The
      total cell and neutrophil counts in BALF were increased from day 3 to 3 months.
      In lung tissue, infiltration of mainly neutrophils and alveolar macrophages was
      observed from day 3 to 6 months in alveoli. These results suggest that CINC was
      involved in lung injury by nickel oxide nanoparticles.

PMID- 19772483
TI  - Chemical analysis of cigarette smoke particulate generated in the MSB-01 in vitro
      whole smoke exposure system.
AB  - Cigarette mainstream smoke (MS) is a dynamic aerosol consisting of a gas-vapor
      phase and a particulate phase. In recent years, novel in vitro whole smoke
      exposure systems have been developed to expose cells directly to whole MS. One
      such system is the Burghart Mimic Smoker-01 (MSB-01). Our previous data using the
      MSB-01 indicated that a 50 +/- 10% loss of particulate matter occurred prior to
      MS delivery into the exposure chamber. Additionally, a change in aerosol particle
      diameter was also measured, suggesting that the chemical composition of MS might
      be changing within the system. In this study, we have expanded on our previous
      work and compared the particulate phase chemical composition of undiluted and
      diluted MS generated by the instrument and that of the MS delivered into the
      exposure chamber. The average percent delivery of cigarette smoke condensate
      (CSC) detected for all the measured chemical constituents was 35 +/- 13% for
      undiluted MS and 23 +/- 8% for 1:1 diluted MS. The data also indicate that under
      our experimental conditions, incomplete mixing of the freshly generated MS occurs
      during its dilution by the system. Taken together, the data presented here show
      that significant chemical changes occur between the generation of MS by the
      system and its delivery into the exposure chamber. This indicates that due to the
      dynamic nature of cigarette smoke, it is important to characterize the exposure
      conditions in order to gain the best insight and accurately correlate exposure
      with biological endpoints.

PMID- 19772484
TI  - Microwave assisted, one-pot synthesis of 5-nitro- 2-aryl substituted-1H
      benzimidazole libraries: screening in vitro for antimicrobial activity.
AB  - The efficient and rapid synthesis of 5-nitro-2-aryl substituted-1H-benzimidazole
      libraries (1a-1j) has been established. Thus, both microwave and conventional
      cyclo-condensation of 4-nitro ortho-phenylenediamine with various phenoxyacetic
      acids were carried out in the presence of HCl catalyst. The microwave synthesis
      route afforded advantages, such as good to excellent yields, shorter reaction
      time (2.5-3.5 min), readily available starting material, and simple purification
      procedure, which distinguish the present protocol from other existing methods
      used for the synthesis of benzimidazole libraries. Bioassay indicated that all
      the compounds showed in vitro antimicrobial activity against Vancomycin resistant
      enteroccoccus, Staphylococcus aureus, Micrococcus, Bacillus subtilis (gram
      positive bacteria) and Shigella dysentery, Escherichia coli (gram-negative
      bacteria) and Candida albicans, Aspergillus niger, Penicillium (fungi). The
      minimum inhibitory concentration (MIC) was determined for test compounds as well
      as for reference standards.

PMID- 19772485
TI  - Galinsosides A and B, bioactive flavanone glucosides from Galinsoga parviflora.
AB  - Galinsosides A (1) and B (2), new flavanone glucosides together with two known
      flavanones, 7,3',4'-trihydroxyflavanone (3) and 3,5,7,3',4'-pentahydroxyflavanone
      (4) have been isolated from an ethyl acetate- soluble fraction of Galinsoga
      parviflora. Their structures were assigned on the basis of spectral studies.
      Compound 1 showed significant antioxidant and urease inhibitory activity while
      compound 2 was moderately active. On the other hand, 2 showed inhibitory
      potential against alpha-glucosidase.

PMID- 19772486
TI  - Chemical constituents isolated from Paeonia lactiflora roots and their
      neuroprotective activity against oxidative stress in vitro.
AB  - The methanolic extract of Paeonia lactiflora roots significantly protected
      primary cultures of rat cortical cells exposed to oxidative stress induced by
      H(2)O(2). Seven monoterpenes, paeonilactone-B (1), paeonilactone-C (2),
      paeoniflorigenone (3), benzoylpaeoniflorin (4), paeoniflorin (5), oxypaeoniflorin
      (6) and albiflorin (7), were isolated by bioactivity-guided fractionation and
      further separation using chromatographic techniques. Among them, compounds 2 and
      4 significantly protected primary cultures of rat cortical cells against H(2)O(2)
      induced neurotoxicity.

PMID- 19772487
TI  - Screening and evaluation of antioxidant activity of some amido-carbonyl oxime
      derivatives and their radical scavenging activities.
AB  - The antioxidant activity of some amido-carbonyl oximes containing a C=O and -NH-R
      adjacent to the oxime group, [Phenyl-C(=O)-C(=N-OH)-N(-H)-Phenyl(-R)] where R= H,
      4-chloro, 4-methyl, 4-methoxy, 3,4-dichloro, 3,4-dimethyl, 3-chloro-4-dimethyl, 3
      chloro-4-methoxy, naphthyl and an amido-carbonyl dioxime were investigated in
      vitro by ferric thiocyanate, total reducing power by potassium ferricyanide
      reduction, 1,1-diphenyl-2- picryl-hydrazyl (DPPH(.)) free radical scavenging,
      ferrous ions chelating, superoxide anion radical scavenging and hydrogen peroxide
      scavenging activity assays. The results indicated that the amido-carbonyl oximes
      have powerful antioxidant capacity.

PMID- 19772488
TI  - Tyrosinase inhibitory effect and inhibitory mechanism of tiliroside from
      raspberry.
AB  - Tiliroside was found to inhibit both monophenolase and diphenolase activity of
      mushroom tyrosinase. The lag time of tyrosine oxidation catalyzed by mushroom
      tyrosinase was obviously lengthened; 0.337 mM of tiliroside resulted in the lag
      time extension from 46.7 s to 435.1 s. A kinetic analysis shown that tiliroside
      was a competitive inhibitor for monophenolase and diphenolase with K(i) values of
      0.052 mM and 0.26 mM, respectively. Furthermore, tiliroside showed 34.5% (p <
      0.05) inhibition of intracellular tyrosinase activity and 54.1% (p < 0.05)
      inhibition of melanin production with low cytotoxicity on B16 mouse melanoma
      cells at 0.168 mM. In contrast, arbutin displayed 9.1% inhibition of cellular
      tyrosinase activity and 29.5% inhibition of melanin production at the same
      concentration. These results suggested that tiliroside was a potent tyrosinase
      inhibitor and might be used as a skin-whitening agent and pigmentation medicine.

PMID- 19772489
TI  - Synthesis, antimicrobial and antiviral activity of substituted benzimidazoles.
AB  - In the present study we have synthesized (4-nitrophenyl)-[2-(substituted phenyl)
      benzoimidazol-1-yl]-methanones, (2-bromophenyl)-[2-(substituted phenyl)
      benzoimidazol-1-yl]-methanone analogues (1-14) and evaluated them for their
      antimicrobial and antiviral potential. The results of antimicrobial screening
      indicated that none of the synthesized compounds were effective against the
      tested bacterial strains. Compounds 3, 11, 13 and compounds 5, 11, 12 were found
      to be active against Aspergillus niger and Candida albicans respectively, and may
      be further developed as antifungal agents. Furthermore, evaluation against a
      panel of different viruses pointed out the selective activity of compounds 5 and
      6 against vaccinia virus and Coxsackie virus B4.

PMID- 19772490
TI  - Synthesis and biological evaluation of O-methyl and O-ethyl NSAID hydroxamic
      acids.
AB  - This paper reports the synthesis of O-methyl and O-ethyl NSAID hydroxamic acids,
      their antimicrobial activities, and their ability to inhibit urease and soybean
      lipoxygenase activities. Ibuprofen and fenoprofen hydroxamic acids with free
      hydroxy groups present the highest antimicrobial activity, while indomethacin and
      diclofenac analogs show significantly lower antimicrobial activity. Diclofenac
      hydroxamic acid 4e exerts the highest anti-urease activity. Indomethacin O-ethyl
      hydroxamic acid 3h and ibuprofen O-benzyl hydroxamic acid 4b exert significant
      inhibitory activities on soybean lipoxygenase. Fenoprofen and indomethacin O
      ethyl hydroxamic acids 3b and 3h and diclofenac and indomethacin O-benzyl analogs
      4g and 4i highly inhibit lipid peroxidation. The highest antioxidant activity was
      shown by fenoprofen derivative 3b.

PMID- 19772491
TI  - Kukoamine A analogs with lipoxygenase inhibitory activity.
AB  - Kukoamine A (KukA) is a spermine (SPM) conjugate with dihydrocaffeic acid (DHCA),
      with interesting biological activities. The four possible regioisomers of KukA,
      as well as a series of KukA analogs incorporating changes in either the SPM or
      the DHCA structural units, were evaluated for their antioxidant activity and
      their inhibitory activity on soybean lipoxygenase (LOX) and lipid peroxidation.
      The reducing properties of the compounds were evaluated using the 1,1-diphenyl-2
      picrylhydrazyl (DPPH) free radical scavenging assay and found to be in the range
      5-97.5%. KukA significantly inhibits LOX with IC(50) 9.5 microM. All tested
      analogs inhibited lipid peroxidation in the range of 11-100%. The most potent
      compounds KukA and its analog 3, in which the DHCA units had been replaced by
      O,O9-dimethylcaffeic acid units, were studied for their anti-inflammatory
      activity in vivo on rat paw edema induced by carrageenan and found to be of
      comparable activity to indomethacin. The results of the biological tests are
      discussed in terms of structural characteristics.

PMID- 19772492
TI  - A series of cinnamic acid derivatives and their inhibitory activity on intestinal
      alpha-glucosidase.
AB  - Inhibition of alpha-glucosidase and alpha-amylase delays the digestion of starch
      and disaccharides to absorbable monosaccharides, resulting in a reduction of
      postprandial hyperglycemia. Finding effective mammalian alpha-glucosidase
      inhibitors from natural sources can be beneficial in the prevention and treatment
      of diabetes mellitus. We investigated the inhibitory activity of cinnamic acid
      derivatives against rat intestinal alpha-glucosidase and porcine pancreatic alpha
      amylase in vitro. Among 11 cinnamic acid derivatives, caffeic acid, ferulic acid,
      and isoferulic acid were the most potent inhibitors against intestinal maltase
      with IC(50) values of 0.74 +/- 0.01, 0.79 +/- 0.04, and 0.76 +/- 0.03 mM,
      respectively, whereas ferulic acid (IC(50) = 0.45 +/- 0.01 mM) and isoferulic
      acid (IC(50) = 0.45 +/- 0.01 mM) were effective intestinal sucrase inhibitors.
      However, all cinnamic acid derivatives were found to be inactive in pancreatic
      alpha-amylase inhibition. Kinetic analysis revealed that intestinal maltase was
      inhibited by caffeic acid, ferulic acid, and isoferulic acid in a mixed
      inhibition manner. In addition, ferulic acid and isoferulic acid inhibited
      intestinal sucrase in a mixed type manner, whereas caffeic acid was a non
      competitive inhibitor. The combination of isoferulic acid and acarbose showed an
      additive inhibition on intestinal sucrase. This study could provide a new insight
      into naturally occurring intestinal alpha-glucosidase inhibitors that could be
      useful for treatment of diabetes and its complications.

PMID- 19772493
TI  - Synthesis, spectroscopic, and antibacterial activity of tetraazamacrocyclic
      complexes of trivalent chromium, manganese, and iron.
AB  - A new series of macrocyclic complexes of type [M(TML)X]X(2), where M = Cr(III),
      Mn(III), or Fe(III), TML is tetradentate macrocyclic ligand, and X = Cl(-),
      NO(3)(-), CH(3)COO(-) for Cr(III), Fe(III) and X = CH(3)COO(-) for Mn (III), has
      been synthesized by condensation of benzil and succinyldihydrazide in the
      presence of metal salt. The complexes have been so formulated due to the 1:2
      electrolytic nature of these complexes as shown by conductivity measurements. The
      complexes have been characterized with the help of various physicochemical
      techniques such as elemental analysis, molar conductance, electronic and infrared
      spectral studies, and magnetic susceptibility. On the basis of these studies, a
      five-coordinate distorted square pyramidal geometry, in which two nitrogens and
      two carbonyl oxygen atoms are suitably placed for coordination toward the metal
      ion, has been proposed for all the complexes. The complexes have been tested for
      their in vitro antibacterial activity. Some of the complexes show remarkable
      antibacterial activities against some selected bacterial strains. The minimum
      inhibitory concentrations shown by these complexes have been compared with those
      shown by some standard antibiotics such as linezolid and cefaclor.

PMID- 19772494
TI  - The plant endoplasmic reticulum: a cell-wide web.
AB  - The ER (endoplasmic reticulum) in higher plants forms a pleomorphic web of
      membrane tubules and small cisternae that pervade the cytoplasm, but in
      particular form a polygonal network at the cortex of the cell which may be
      anchored to the plasma membrane. The network is associated with the actin
      cytoskeleton and demonstrates extensive mobility, which is most likely to be
      dependent on myosin motors. The ER is characterized by a number of domains which
      may be associated with specific functions such as protein storage, or with direct
      interaction with other organelles such as the Golgi apparatus, peroxisomes and
      plastids. In the present review we discuss the nature of the network, the role of
      shape-forming molecules such as the recently described reticulon family of
      proteins and the function of some of the major domains within the ER network.

PMID- 19772496
TI  - [Oxidized fibrinogen and its relationship with hemostasis disturbances and
      endothelial dysfunction during coronary heart disease and myocardial infarction].
AB  - The highest oxidative modification of fibrinogen was found in acute myocardial
      infarction (MI) men and it was 1.26 and 1.56 times higher in comparison with
      coronary heart disease (CHD) men with anamnesis of MI and with men without CHD,
      respectively. Increased oxidized fibrinogen level correlated with increased
      levels of plasma lipid peroxidation products, Willebrand factor, fibrin
      degradation products, accelerated leukocyte-platelet aggregation and decreased
      level of plasma NO metabolites. Associations of oxidized fibrinogen with MI and
      typical parameters of thrombosis and hypercoagulatory hemostasis disturbances and
      endothelial function were revealed.

PMID- 19772497
TI  - [Factors associated with low ankle-brachial index in patients with type 2
      diabetes and prediabetes].
AB  - PURPOSE: To elucidate factors associated with an established marker of occlusive
      atherosclerosis of lower extremities - low ankle-brachial index (ABI) - in
      patients with diabetes mellitus or prediabetes. METHODS: We examined 182 patients
      with diabetes (n=158), impaired glucose tolerance (n=17), or impaired fasting
      glucose (n=7). We analyzed history, demographic parameters, anthropometric data
      (body mass index [BMI], waist circumference), levels of plasma high and low
      density lipoprotein cholesterol, triglycerides, degree of glycemic control, and
      presence of signs of atherosclerosis of other localizations. RESULTS: ABI was <
      or = 0.9 in 47/182 patients (23.6%). Patients with ABI < or = 0.9 were older,
      more often had history of smoking (p<0.001). They also had higher leukocyte count
      (p=0.002). Body mass index was elevated in most patients, however it was lower in
      those with decreased ABI (29.8+/-4.4 and 32.1+/-5.2 in patients with ABI < or =
      0.9 and >0.9, respectively, p=0.006). Factors independently related to ABI < or =
      0.9 were age (OR 1.12; 95%CI 1.05-1.19; p=<0,001), history of smoking (OR 7.06,
      95%CI 2.23-22.3, p=0.001), leukocyte count (OR 1.36; 95% CI 1.05-1.75, p=0.019),
      and BMI (OR 0.856, 95%CI 0.768-0.995). Leukocyte count above 7.6 x 10(3)/mm(3)
      compared with that < or = 7.6 x 10(3)/mm(3) was associated with more than 3 fold
      increase of OR (3.38, 95%CI 1.49-7.48, p=0.003). BMI <30.8 conferred almost
      similar increase of risk to have ABI < or = 0.9 (OR 2.9, 95%CI 1.28-6.73,
      p=0.011). None of biochemical parameters including characteristics of control of
      glycemia was related to the presence of low ABI. CONCLUSION: In this group of
      mostly overweight patients with type 2 diabetes and prediabetes besides such
      classical factors as age and smoking white blood cells count but not lipids were
      associated with low ABI. Observed association of low ABI with smaller BMI within
      overall increased range is in line with some recent clinical reports but requires
      confirmation in specially designed studies.

PMID- 19772498
TI  - [Structural-functional changes of walls of common carotid and brachial arteries
      in hypertensive disease and ischemic heart disease].
AB  - With the help of ultrasound methods of investigation we carried out comparison of
      structural-functional and hemodynamic properties of common carotid and brachial
      arteries in patients with hypertensive disease (HD) including those with
      concomitant ischemic heart disease (IHD) and in subjects of control group.
      Patients with HD combined with IHD compared with patients of other groups had
      more pronounced manifestations of rigidity of carotid arteries walls and
      statistically significant lowering of velocity of intravascular blood flow.

PMID- 19772495
TI  - Mechanisms of double-strand break repair in somatic mammalian cells.
AB  - DNA chromosomal DSBs (double-strand breaks) are potentially hazardous DNA
      lesions, and their accurate repair is essential for the successful maintenance
      and propagation of genetic information. Two major pathways have evolved to repair
      DSBs: HR (homologous recombination) and NHEJ (non-homologous end-joining).
      Depending on the context in which the break is encountered, HR and NHEJ may
      either compete or co-operate to fix DSBs in eukaryotic cells. Defects in either
      pathway are strongly associated with human disease, including immunodeficiency
      and cancer predisposition. Here we review the current knowledge of how NHEJ and
      HR are controlled in somatic mammalian cells, and discuss the role of the
      chromatin context in regulating each pathway. We also review evidence for both co
      operation and competition between the two pathways.

PMID- 19772499
TI  - [The use of atorvastatin in patients with rheumatoid arthritis with
      hyperlipidemia].
AB  - AIM: To assess efficacy and tolerability of atorvastatin and its lipid lowering
      and antiinflammatory effects as well as action on function of endothelium and
      elastic properties of arteries in patients with rheumatoid arthritis (RA) and
      hyperlipidemia. MATERIAL: Patients with RA (n=50) were divided into 2 groups. The
      main group comprised 30 patients receiving atorvastatin (10 mg/day) as a
      component of complex therapy. The group of comparison comprised 20 patients with
      similar clinical characteristics and baseline lipid levels. RESULTS: The use of
      atorvastatin in complex therapy led not only to lowering of levels of atherogenic
      fractions of lipids but also to substantial lowering of levels of systemic
      inflammation and diminishment of endothelial damage. Positive action of 6 month
      therapy with atorvastatin on elastic properties of arteries was demonstrated.
      Tolerability of atorvastatin was good. CONCLUSION: The data obtained allow to
      recommend the use of atorvastatin for long term management of hyperlipidemia in
      patients with RA.

PMID- 19772500
TI  - [Comparative transcriptome analysis of human aorta atherosclerotic lesions and
      peripheral blood leukocytes from essential hypertension patients].
AB  - One of the major cardiovascular risk factor which predisposes to and accelerates
      atherosclerosis is arterial hypertension (AH). To determine the molecular basis
      of the crosslink between AH and atherosclerosis for the development of new
      treatment strategies large-scale transcriptome analysis of the cells implicated
      in atherogenesis is needed. We used cDNA microarray technique for simultaneous
      analysis of gene expression in human abdominal aorta normal sites and
      atherosclerotic lesions of different histological types, as well as in peripheral
      blood leukocytes from patients with essential hypertension (EH) and donors. The
      microarray data were verified by quantitative RT-PCR (reverse transcription
      coupled with polymerase chain reaction) and immunohistochemical analysis.
      Differential expression of 40 genes has been found, among which twenty two genes
      demonstrated up-regulation and 18 genes demonstrated down-regulation in
      atherosclerotic aorta compared with normal vessel. New gene-candidates,
      implicated in atherogenesis, have been identified - FPRL2, CD37, CD53, RGS1,
      LCP1, SPI1, CTSA, EPAS1, FHL1, GEM, RHOB, SPARCL1, ITGA8, PLN, and COL14A1. These
      genes participate in cell migration and adhesion, phenotypic changes of smooth
      muscle cells, immune and inflammatory reactions, oxidative processes and
      extracellular matrix remodeling. We have found increased expression levels of
      CD53, SPI1, FPRL2, SPP1, CTSD, ACP5, LCP1, CTSA and LIPA genes in peripheral
      blood leukocytes from EH patients and in atherosclerotic lesions of human aorta.
      The majority of these genes significantly (p<0.005) positively (r>0.5) correlated
      with AH stage as well as with histological grading of atherosclerotic lesions.

PMID- 19772501
TI  - [Possibilities of dopplerography in assessment of functional state of the heart
      in patients with arterial hypertension with impaired diastolic cardiac function].
AB  - The search for reliable Dopplerographic markers of incipient diastolic cardiac
      failure became especially actual in recent years. We examined 71 patients with II
      degree arterial hypertension (AH) with Dopplerographical signs of diastolic left
      ventricular (LV) dysfunction. For the assessment of severity of diastolic
      dysfunction we carried out complex Dopplerographic evaluation of maximal
      velocities of transmitral blood flow and motion of fibrous annulus of the mitral
      valve (MV). We revealed relationships between standard parameters of transmitral
      flow, Doppler visualization of tissues, and tolerance to physical effort. We
      found moderate negative correlation between exercise tolerance and maximal
      velocity of movement of lateral part of MV fibrous annulus E' (r=-0.4, p=<0.001),
      E/E' ratio (r=-0.65, p=<0.001). E/E' ratio had the strongest linear relationship
      with exercise tolerance. We showed that combined assessment of velocity of early
      LV diastolic filling and velocity of MV fibrous annulus motion (E/E') was
      possible in all patients with preserved LV systolic function. In patients with AH
      without myocardial hypertrophy with incipient LV diastolic dysfunction increase
      of E/E' > or = 10 allows to suggest lowering of exercise tolerance and might be
      indicative of early signs of diastolic heart failure.

PMID- 19772502
TI  - [Effect of arterial hypertension on sexual health of men and their quality of
      life. Resuts of BOLERO study].
AB  - Analysis of results of epidemiological BOLERO study showed that 2/3 of men with
      uncontrolled arterial hypertension noted problems in sexual life. Severity of
      problems in this sphere of life of men correlated positively with age, as well as
      with presence of difficulties at work, increased fatigability, impossibility to
      be involved in favorite activity (hobby), disturbances of nocturnal sleep (as
      assessed by GQLI questionnaire). As a result of 8 weeks therapy which included
      indapamide retard number of patients noting substantial influence of sexual
      problems on their habitual way of life (CQLI score >3) decreased almost 2 times
      (from 25 to 13%, p<0,001). At least 1 point decrease in evaluation of importance
      of such problems occurred in 33% of cases, 63% of patients did not change their
      score. An increase of GQLI score was noted in 4% of cases. Multifactorial
      analysis allowed to reveal that restoration of sexual function went parallel with
      improvement of quality of life related to recovery of psychosocial relationships
      and augmentation of physical activity. Moreover it was established that adequate
      lowering of arterial pressure in men during use of indapamide retard decreased
      risk of worsening of their sexual function.

PMID- 19772503
TI  - [Disturbances of primary hemostasis in patients with dilation cardiomyopathy].
AB  - We studied morphological characteristics of platelets and parameters of platelet
      aggregation in patients with dilation cardiomyopathy. Augmented aggregatory
      activity of platelets was found in 76% of patients. In blood of majority of
      patients we found circulating leukocyte-platelet aggregates. This evidenced for
      development of inflammatory process and could be related to disturbances of blood
      rheology. In 2 patients examined by virusological method we revealed presence of
      a virus inside platelets. This phenomenon might serve as one of possible
      pathological pathways of disease progression at the account of spread of viral
      infection along vascular bed during thrombus formation.

PMID- 19772504
TI  - [Clinical and prognostic significance of left bundle branch block in patients
      with severe chronic heart failure].
AB  - Clinical and prognostic significance of left bundle branch block (LBBB) was
      investigated in 62 elderly patients with severe chronic heart failure (CHF). In
      comparison to 93 patients with CHF but without intra-ventricular blocks patients
      with LBBB demonstrated more frequently atrial fibrillation and left ventricular
      systolic dysfunction but less frequently chronic obstructive pulmonary disease,
      anemia and a history of myocardial infarction. Fourth-year follow-up showed that
      LBBB was not important predictor of survival in patients with severe CHF.

PMID- 19772505
TI  - [Nonspecific markers of inflammation in prognostication of the course of ischemic
      heart disease].

PMID- 19772506
TI  - [Left bundle of his brunch block as a manifestation of the syndrome of
      dromotropic insufficiency in patients with chronic heart failure].
AB  - Left bundle brunch block (LBBB) is met in approximately 20% of hospitalized
      patients and in 1/3 of outpatients with chronic heart failure (CHF). Abnormalites
      of impulse conduction in LBBB promote dyssynchronization, which represent a
      pathophysiological process which not only worsens ventricular function but also
      facilitates remodeling of the myocardium and development of CHF. As a result of
      dyssynchrony systolic and diastolic functions of the heart are impaired. This
      manifests as shortening of diastole of the left ventricle and dyssynchronous
      movement of interventricular septum (IVS) with a tendency to lowering of local
      and global ejection fraction (EF), and leads to significant metabolic and
      energetic consequences. Abnormal geometry and dilation of the heart in CHF
      promotes chaotic separation of early and late activated myocardial zones. This
      aggravates disturbances of conduction existing as a result of fibrosis and causes
      weakening of contractility and slowing of impulse conduction velocity. These
      morphological changes facilitate electrophysiological deviations and formation of
      abnormal conduction. LBBB is undoubtedly involved in development of sudden death
      of patients with CHF, but its effect on long term prognosis remains ambiguous and
      possibly the role of no small importance in this belongs to severe concomitant
      pathology and dysfunction of left ventricular myocardium.

PMID- 19772507
TI  - [Diagnosis and treatment of disturbances of lipid metabolism in children and
      adolescents].
AB  - It has been demonstrated in prospective and epidemiological studies that
      excessive consumption of saturated and trans-fats, refined carbohydrates,
      epidemic of obesity and metabolic syndrome in children and adolescents have
      prognostic value in relation to development of cardiovascular diseases (CVD) in
      adults. Pediatricians should initiate long-term prevention of CVD in early age.
      At present there are scientific data on safety and efficacy of drugs in the
      treatment of dyslipidemia in adolescent age. A review of clinical studies on
      detection, diagnosis, prevention, and drug correction of lipid disturbances among
      children and adolescents is presented in this paper. Main statements of
      recommendations of American Academy of Pediatrics "Cholesterol in Childhood" are
      analyzed in detail.

PMID- 19772508
TI  - [Pacing in elderly recurrent fallers with carotid sinus hypersensitivity:A
      randomized, double-blind placebo controlled crossover trial].

PMID- 19772509
TI  - [Heart rate and acute coronary syndrome: crosslink mechanisms and possibilities
      of drug intervention].
AB  - Studies in general population, in elderly people, and in groups of patients with
      arterial hypertension, myocardial infarction, stable coronary heart disease,
      diabetes mellitus, and after coronary bypass surgery have shown that elevated
      heart rate (HR) is prognostically unfavorable factor of cardiovascular and total
      mortality independent of other risk factors. Moreover, it has been shown that
      tachycardia to a certain extent correlates with severity and progression of
      atherosclerosis and can promote damage of integrity of atherosclerotic plaque.
      Plaque rupture plays main role in pathogenesis of acute coronary syndrome (ACS).
      Lowering of HR is one of therapeutic approaches to prevention of plaque rupture,
      i.e. to lowering of risk of ACS development. Mechanisms of interrelationships
      between HR and ACS and possibilities to influence HR with drugs in ACS are
      presented in this review.

PMID- 19772510
TI  - [Chronic heart failure with preserved ejection fraction: pathophysiology,
      diagnosis, strategies of treatment].

PMID- 19772511
TI  - Infant feeding and allergy prevention: a review of current knowledge and
      recommendations. A EuroPrevall state of the art paper.
AB  - The relationship between infant feeding patterns and the later development of
      food allergies has been the focus of much debate and research over the last
      decade. National recommendations have been made by many countries on how to feed
      infants to reduce the risk of food allergy but due to the lack of firm evidence
      the recommendations differ widely. This review has been developed as part of
      EuroPrevall, a European multicentre research project funded by the European
      Union, to document the differing feeding recommendations made across Europe, to
      investigate the current evidence base for any allergy prevention feeding
      recommendations and to identify areas where further research is needed. This
      review will also provide information which, when combined with the infant feeding
      data collected as part of EuroPrevall, will give an indication of compliance to
      national feeding guidelines which can be utilised to assess the effectiveness of
      current dissemination and implementation strategies.

PMID- 19772512
TI  - EAACI/GA(2)LEN/EDF/WAO guideline: definition, classification and diagnosis of
      urticaria.
AB  - This guideline, together with its sister guideline on the management of urticaria
      [Zuberbier T, Asero R, Bindslev-Jensen C, Canonica GW, Church MK, Gimenez-Arnau
      AM et al. EAACI/GA(2)LEN/EDF/WAO Guideline: Management of urticaria. Allergy,
      2009; 64:1427-1443] is the result of a consensus reached during a panel
      discussion at the 3rd International Consensus Meeting on Urticaria, Urticaria
      2008, a joint initiative of the Dermatology Section of the European Academy of
      Allergology and Clinical Immunology (EAACI), the EU-funded network of excellence,
      the Global Allergy and Asthma European Network (GA(2)LEN), the European
      Dermatology Forum (EDF) and the World Allergy Organization (WAO). Urticaria is a
      frequent disease. The life-time prevalence for any subtype of urticaria is
      approximately 20%. Chronic spontaneous urticaria and other chronic forms of
      urticaria do not only cause a decrease in quality of life, but also affect
      performance at work and school and, as such, are members of the group of severe
      allergic diseases. This guideline covers the definition and classification of
      urticaria, taking into account the recent progress in identifying its causes,
      eliciting factors, and pathomechanisms. In addition, it outlines evidence-based
      diagnostic approaches for different subtypes of urticaria. The correct management
      of urticaria, which is of paramount importance for patients, is very complex and
      is consequently covered in a separate guideline developed during the same
      consensus meeting. This guideline was acknowledged and accepted by the European
      Union of Medical Specialists (UEMS).

PMID- 19772513
TI  - EAACI/GA(2)LEN/EDF/WAO guideline: management of urticaria.
AB  - This guideline, together with its sister guideline on the classification of
      urticaria (Zuberbier T, Asero R, Bindslev-Jensen C, Canonica GW, Church MK,
      Gimenez-Arnau AM et al. EAACI/GA(2)LEN/EDF/WAO Guideline: definition,
      classification and diagnosis of urticaria. Allergy 2009;64: 1417-1426), is the
      result of a consensus reached during a panel discussion at the Third
      International Consensus Meeting on Urticaria, Urticaria 2008, a joint initiative
      of the Dermatology Section of the European Academy of Allergology and Clinical
      Immunology (EAACI), the EU-funded network of excellence, the Global Allergy and
      Asthma European Network (GA(2)LEN), the European Dermatology Forum (EDF) and the
      World Allergy Organization (WAO). As members of the panel, the authors had
      prepared their suggestions regarding management of urticaria before the meeting.
      The draft of the guideline took into account all available evidence in the
      literature (including Medline and Embase searches and hand searches of abstracts
      at international allergy congresses in 2004-2008) and was based on the existing
      consensus reports of the first and the second symposia in 2000 and 2004. These
      suggestions were then discussed in detail among the panel members and with the
      over 200 international specialists of the meeting to achieve a consensus using a
      simple voting system where appropriate. Urticaria has a profound impact on the
      quality of life and effective treatment is, therefore, required. The recommended
      first line treatment is new generation, nonsedating H(1)-antihistamines. If
      standard dosing is not effective, increasing the dosage up to four-fold is
      recommended. For patients who do not respond to a four-fold increase in dosage of
      nonsedating H(1)-antihistamines, it is recommended that second-line therapies
      should be added to the antihistamine treatment. In the choice of second-line
      treatment, both their costs and risk/benefit profiles are most important to
      consider. Corticosteroids are not recommended for long-term treatment due to
      their unavoidable severe adverse effects. This guideline was acknowledged and
      accepted by the European Union of Medical Specialists (UEMS).

PMID- 19772514
TI  - Regular vs prn nebulized treatment in wheeze preschool children.
AB  - BACKGROUND: International guidelines recommend regular treatment with inhaled
      glucocorticoids for children with frequent wheezing; however, prn inhaled
      bronchodilator alone or in combination with glucocorticoid is also often used in
      practice. We aimed to evaluate whether regular nebulized glucocorticoid plus a
      prn bronchodilator or a prn nebulized bronchodilator/glucocorticoid combination
      is more effective than prn bronchodilator alone in preschool children with
      frequent wheeze. METHODS: Double-blind, double-dummy, randomized, parallel-group
      trial. After a 2-week run-in period, 276 symptomatic children with frequent
      wheeze, aged 1-4 years, were randomly assigned to three groups for a 3-month
      nebulized treatment: (1) 400 microg beclomethasone bid plus 2500 microg
      salbutamol prn; (2) placebo bid plus 800 microg beclomethasone/1600 microg
      salbutamol combination prn; (3) placebo bid plus 2500 microg salbutamol prn. The
      percentage of symptom-free days was the primary outcome measure. Secondary
      outcomes included symptom scores, use of relief medication and exacerbation
      frequency. RESULTS: As compared with prn salbutamol (61.0 +/- 24.83 [SD]), the
      percentage of symptom-free days was higher with regular beclomethasone (69.6%, SD
      20.89; P = 0.034) but not with prn combination (64.9%, SD 24.74). Results were no
      different in children with or without risk factors for developing persistent
      asthma. The effect of prn combination was no different from that of regular
      beclomethasone on the primary and on several important secondary outcomes.
      CONCLUSIONS: Regular inhaled glucocorticoid is the most effective treatment for
      frequent wheezing in preschool children. However, prn
      bronchodilator/glucocorticoid combination might be an alternative option, but it
      requires further study.

PMID- 19772516
TI  - GA(2)LEN skin test study II: clinical relevance of inhalant allergen
      sensitizations in Europe.
AB  - BACKGROUND: Skin prick testing is the standard for diagnosing IgE-mediated
      allergies. A positive skin prick reaction, however, does not always correlate
      with clinical symptoms. A large database from a Global Asthma and Allergy
      European Network (GA(2)LEN) study with data on clinical relevance was used to
      determine the clinical relevance of sensitizations against the 18 most frequent
      inhalant allergens in Europe. The study population consisted of patients referred
      to one of the 17 allergy centres in 14 European countries (n = 3034, median age =
      33 years). The aim of the study was to assess the clinical relevance of positive
      skin prick test reactions against inhalant allergens considering the
      predominating type of symptoms in a pan-European population of patients
      presenting with suspected allergic disease. METHODS: Clinical relevance of skin
      prick tests was recorded with regard to patient history and optional additional
      tests. A putative correlation between sensitization and allergic disease was
      assessed using logistic regression analysis. RESULTS: While an overall rate of
      >or=60% clinically relevant sensitizations was observed in all countries, a
      differential distribution of clinically relevant sensitizations was demonstrated
      depending on type of allergen and country where the prick test was performed.
      Furthermore, a significant correlation between the presence of allergic disease
      and the number of sensitizations was demonstrated. CONCLUSION: This study
      strongly emphasizes the importance of evaluating the clinical relevance of
      positive skin prick tests and calls for further studies, which may, ultimately,
      help increase the positive predictive value of allergy testing.

PMID- 19772515
TI  - GA(2)LEN skin test study I: GA(2)LEN harmonization of skin prick testing: novel
      sensitization patterns for inhalant allergens in Europe.
AB  - BACKGROUND: Skin prick testing is the standard for diagnosing IgE-mediated
      allergies. However, different allergen extracts and different testing procedures
      have been applied by European allergy centres. Thus, it has been difficult to
      compare results from different centres or studies across Europe. It was,
      therefore, crucial to standardize and harmonize procedures in allergy diagnosis
      and treatment within Europe. AIMS: The Global Asthma and Allergy European Network
      (GA(2)LEN), with partners and collaborating centres across Europe, was in a
      unique position to take on this task. The current study is the first approach to
      implement a standardized procedure for skin prick testing in allergies against
      inhalant allergens with a standardized pan-European allergen panel. METHODS: The
      study population consisted of patients who were referred to one of the 17
      participating centres in 14 European countries (n = 3034, median age = 33 years).
      Skin prick testing and evaluation was performed with the same 18 allergens in a
      standardized procedure across all centres. RESULTS: The study clearly shows that
      many allergens previously regarded as untypical for some regions in Europe have
      been underestimated. This could partly be related to changes in mobility of
      patients, vegetation or climate in Europe. CONCLUSION: The results of this large
      pan-European study demonstrate for the first time sensitization patterns for
      different inhalant allergens in patients across Europe. The standardized skin
      prick test with the standardized allergen battery should be recommended for
      clinical use and research. Further EU-wide monitoring of sensitization patterns
      is urgently needed.

PMID- 19772517
TI  - United airways: the impact of chronic rhinosinusitis and nasal polyps in
      bronchiectasic patient's quality of life.
AB  - BACKGROUND: The nose and the bronchi belong, in anatomical and physiopathological
      terms, to the concept of united airways. Associations between upper and lower
      airways diseases have been demonstrated in allergic rhinitis and asthma, nasal
      polyposis (NP) and asthma, chronic rhinosinusitis (CRS) and chronic obstructive
      pulmonary disease, and more recently CRS/NP and bronchiectasis (BQ). OBJECTIVE:
      To evaluate the impact of CRS on quality of life (QoL) of patients with BQ, and
      to correlate these findings with the pulmonary status, nasal symptoms, and
      general health status. METHODS: In a prospective study, patients with BQ (n = 80)
      were evaluated for CRS and NP using EP(3)OS criteria, and severity of BQ using
      chest high resolution computed tomography (HRCT)-scan. Quality of life was
      assessed in all patients by using specific [Sinonasal Outcome Test-20 (SNOT-20),
      St George Respiratory Questionnaire (SGRQ)], and generic (Short Form-36; SF-36)
      questionnaires. RESULTS: Using SNOT-20, patients with CRS had worse QoL (2.1 +/-
      0.1; P < 0.001) than patients without CRS (0.4 +/- 0.06). Using SGRQ total score,
      patients with CRS had worse QoL (43.7 +/- 2.2; P < 0.001) than patients without
      CRS (24.7 +/- 2.5). Using SF-36, patients with CRS had worse QoL, both in the
      physical summary (64 +/- 3.4; P < 0.05) and the mental summary (65.5 +/- 4.7; P <
      0.05), than patients without CRS (physical summary [PS]: 76.2 +/- 3.3; mental
      summary [MS]: 78.3 +/- 5.3, respectively). Sinonasal Outcome Test-20 was
      correlated with SGRQ total score (r = 0.72; P < 0.01), and SF-36 physical summary
      (r = -0.63; P < 0.01). St George Respiratory Questionnaire was correlated with SF
      36 on physical summary (r = -0.58; P < 0.05) and with forced expiratory volume in
      1 s (r = -0.41; P < 0.05). CONCLUSION: These results suggested that CRS, measured
      by both specific and generic questionnaires, has a considerable impact on the QoL
      of patients with BQ.

PMID- 19772518
TI  - Food allergy to chicken meat with IgE reactivity to muscle alpha-parvalbumin.

PMID- 19772519
TI  - Allergy for cheese: evidence for an IgE-mediated reaction from the natural dye
      annatto.

PMID- 19772520
TI  - Levosimendan in viral myocarditis: not only an inodilator but also a
      cardioprotector?

PMID- 19772521
TI  - ESCI award lecture: from a little mouse to rationale medicine for bone loss.
AB  - Completion of the human genome is one of the many significant milestones in the
      new era of systems biology. The current phase of genomic studies is focused upon
      parsing this new found genetic data with respect to scientific interest, and
      economic and health impact applications. As the sequences are now available and
      whole genome single nucleotide polymorphism maps for multiple human diseases will
      be available with the advent of modern genomics, the big challenge is to
      determine the function of these genes in the context of the entire organism. The
      emphasis is therefore on functional genomic analysis that represents the new
      front-line and limiting factor for realizing potential benefits of genome-based
      science. Defined gene targeting has been proven to be particularly useful as loss
      of expression mutants can reveal essential functions of molecules and the
      pathogenesis of disease. Using gene-targeted mice, my group has over the years
      identified genes that control heart and lung functions; apoptosis; lymphocyte
      activation; cancer; pain; diabetes; fertility or wound healing . In this study, I
      would like to review our work on RANKL in more detail.

PMID- 19772522
TI  - Effects of levosimendan in experimental acute coxsackievirus myocarditis.
AB  - BACKGROUND: Acute heart failure is a potentially fatal manifestation of viral
      myocarditis. Development of myocardial damage in myocarditis involves
      cardiomyocyte apoptosis. Levosimendan is a novel calcium sensitizing inotropic
      agent with anti-apoptotic properties. We studied the feasibility of inotropic
      treatment with levosimendan and its effects on apoptosis in experimental acute
      heart failure caused by coxsackievirus myocarditis. MATERIALS AND METHODS:
      Adolescent BALB/c mice were infected with myocarditic Woodruff variant of
      coxsackievirus B3 (2 x 10(4) plaque-forming units). Mice were randomized into
      those receiving levosimendan 0.33 mg kg(-1) (total dose 1 mg kg(-1) day(-1)) (n =
      20) or vehicle (n = 19) given orally by gauge three times a day for 7 days after
      infection. Left ventricular function was evaluated by transthoracic
      echocardiography and the mice were euthanized on day 7. Histopathology, amount of
      virus in the heart (virus titration assay) and cardiomyocyte apoptosis (TUNEL
      assay) were studied. Uninfected untreated control mice were also studied.
      RESULTS: Infection resulted in histopathologically severe myocarditis and
      significant impairment of left ventricular function. Levosimendan treatment
      significantly improved ventricular function (fractional shortening 0.32 +/- 0.04
      vs. 0.23 +/- 0.05, P = 0.005; contractility 0.60 +/- 0.12 vs. 0.39 +/- 0.14, P =
      0.007 and myocardial performance index 0.36 +/- 0.06 vs. 0.62 +/- 0.15, P <
      0.0001) compared with vehicle. Levosimendan also reduced cardiomyocyte apoptosis
      (0.26 +/- 0.08% vs. 0.44 +/- 0.15% in vehicle, P = 0.008), but did not have an
      effect on areas of myocardial necrosis or inflammation, or the amount of virus in
      the heart. Levosimendan treatment did not affect mortality (total mortality 63%).
      CONCLUSIONS; Levosimendan improves ventricular function and inhibits
      cardiomyocyte apoptosis; therefore, it is suggested as a potentially feasible
      therapy in acute heart failure caused by viral myocarditis.

PMID- 19772523
TI  - Phenotypic indications that human sweat glands are a rich source of nestin
      positive stem cell populations.
AB  - BACKGROUND: We have recently shown that the expression of nestin, a
      progenitor/stem cell marker protein, is localized in different mesenchymal
      compartments in human skin including the sweat gland stroma. OBJECTIVES: As other
      exocrine glands are recognized sources of multipotent stem cell populations with
      potential for multilineage differentiation, it was our aim to isolate, expand and
      characterize glandular stem cells from human sweat glands. METHODS: Isolation of
      human sweat glands was based on mechanical and enzymatic digestion of axillary
      skin. Cultivation was performed on collagen-coated cell culture dishes and the
      resulting cell population was investigated at the protein and mRNA level.
      RESULTS: Outgrowing cells of isolated sweat glands showed a high-proliferation
      activity and were characterized by nestin expression in more than 80% of the
      cells. These sweat gland stem cells could be maintained in culture for long
      periods of time and showed spontaneous differentiation into cells representative
      of the different germ layers. CONCLUSIONS: This pilot study provides the first,
      simple protocol for the isolation of adult human nestin-positive stem cells from
      the sweat gland mesenchyme, which promises to provide an easily accessible and
      abundantly available, autologous source of multipotent stem cells for cell-based
      regenerative medicine applications.

PMID- 19772524
TI  - Mechanisms of transforming growth factor beta(1)/Smad signalling mediated by
      mitogen-activated protein kinase pathways in keloid fibroblasts.
AB  - BACKGROUND: Keloids are recognized as benign tumours characterized by
      fibroblastic proliferation and accumulation of extracellular matrix, especially
      collagen deposition. The transforming growth factor (TGF)-beta(1)/Smad pathway
      plays an important role in keloid pathogenesis; however the underlying mechanisms
      are not fully understood. OBJECTIVES: To define further the mechanisms of TGF
      beta(1)/Smad signal transduction mediated by mitogen-activated protein kinases
      (MAPKs), including the extracellular signal-regulated protein kinase (ERK), c-Jun
      N-terminal kinase (JNK) and p38 pathways, in keloid fibroblasts. METHODS: In the
      absence or presence of three MAPK (ERK, JNK and p38)-specific inhibitors, keloid
      fibroblasts were stimulated with exogenous TGF-beta(1) to activate Smad
      signalling. Smad protein expression was measured by
      immunoprecipitation/immunoblotting and immunofluorescence; plasminogen activator
      inhibitor (PAI)-1 transcriptional activity was measured by real-time reverse
      transcriptase-polymerase chain reaction analysis. RESULTS: TGF-beta(1) induced
      Smad2/3 phosphorylation at both the C-terminal and the linker region, thus
      promoting formation of the Smad2/3/4 complex and nuclear translocation, and PAI-1
      mRNA expression in keloid fibroblasts; in addition, TGF-beta(1) decreased
      inhibitory Smad7 expression. Meanwhile, the p38 inhibitor significantly inhibited
      Smad2/3 phosphorylation, especially at the linker region, and furthermore blocked
      Smad2/3/4 complex formation, and thus decreased PAI-1 mRNA expression; decreased
      Smad7 expression induced by TGF-beta(1) was also reversed by the p38 inhibitor.
      The ERK and JNK inhibitors interrupted Smad2/3/4 complex translocation into the
      nucleus and consequently decreased PAI-1 mRNA expression. CONCLUSIONS: These
      results suggested that the ERK, JNK and p38 pathways mediate TGF-beta(1)/Smad
      signal transduction and might be considered as specific targets of drug therapy
      for keloids.

PMID- 19772525
TI  - Experimental inhalation of fragrance allergens in predisposed subjects: effects
      on skin and airways.
AB  - BACKGROUND: Exposure to fragrances is increasingly encountered in the
      environment. Some fragrances are known to be important skin and potential airway
      sensitizers. OBJECTIVES: We investigated whether patients with contact allergy to
      isoeugenol (ISO) or hydroxyisohexyl-3-carboxaldehyde (HICC) would react to
      inhalation exposure at the level of the airways and skin. METHODS: Eleven
      patients sensitized to ISO and 10 patients sensitized to HICC were exposed for 60
      min to 1000 microg m(-3) of these compounds in an exposure chamber at rest, and
      to geraniol 1000 microg m(-3) as a control. Patients wore protective clothing to
      prevent skin exposure. Assessments were performed prior to exposure, and
      immediately, 2, 5, 24 and 72 h afterwards. RESULTS: There were no significant
      changes in lung function but a tendency towards an increased bronchial hyper
      responsiveness after exposure to any of the compounds. Laboratory parameters of
      inflammation did not indicate responses. Single patients reported respiratory
      symptoms unrelated to objective measures. In contrast, the observed skin symptoms
      corresponded to the patients' specific sensitization. Four patients reported
      symptoms compatible with delayed-type hypersensitivity, and two demonstrated a
      flare after ISO. On re-exposure they did not respond to a lower, more realistic
      level of ISO. CONCLUSION: Inhalation of high concentrations of fragrance contact
      allergens apparently poses a risk for some patients of developing manifest
      haematogenic contact dermatitis, while the changes in the respiratory tract are
      limited to symptoms in some subjects without objective changes.

PMID- 19772530
TI  - Light-emitting diode flashlights as effective and inexpensive light sources for
      fluorescence microscopy.
AB  - Light-emitting diodes (LEDs) are becoming more commonly used as light sources for
      fluorescence microscopy. We describe the adaptation of a commercially available
      light-emitting diode flashlight for use as a source for fluorescence excitation.
      This light source is long-lived, inexpensive and is effective for excitation in
      the range of 440-600 nm.

PMID- 19772531
TI  - An improved method for nanogold in situ hybridization visualized with
      environmental scanning electron microscopy.

PMID- 19772532
TI  - Fabrication and evaluation of a near-infrared hyperspectral imaging system.
AB  - This paper describes modifications to a hyperspectral imaging microscope that
      extend its capabilities into the near-infrared (950-1300 nm). The major changes
      include installing a grating, charge-coupled device camera, and lenses and
      filters appropriate for infrared wavelengths. Calibration of the system and
      validation with lead sulfide quantum dots of known emission wavelength is
      reported. Cells from the breast carcinoma cell line SkBr3 were scanned with lead
      sulfide quantum dots that emit at 1100 nm as the background and an image which
      contains the integrated spectral data is presented. We also demonstrate that this
      instrument is capable of detecting the photoluminescence spectra of single-walled
      carbon nanotubes dispersed in aqueous solution.

PMID- 19772533
TI  - Gaussian-Taylor signal-to-noise ratio estimation for scanning electron microscope
      images.
AB  - A new and robust parameter estimation technique, named Gaussian-Taylor
      interpolation, is proposed to predict the signal-to-noise ratio (SNR) of scanning
      electron microscope images. The results of SNR and variance estimation values are
      tested and compared with piecewise cubic Hermite interpolation, quadratic spline
      interpolation, autoregressive moving average and moving average. Overall, the
      proposed estimations for noise-free peak and SNR are most consistent and accurate
      to within a certain acceptable degree compared with the others.

PMID- 19772534
TI  - A compact STED microscope providing 3D nanoscale resolution.
AB  - The advent of supercontinuum laser sources has enabled the implementation of
      compact and tunable stimulated emission depletion fluorescence microscopes for
      imaging far below the diffraction barrier. Here we report on an enhanced version
      of this approach displaying an all-physics based resolution down to (19 +/- 3) nm
      in the focal plane. Alternatively, this single objective lens system can be
      configured for 3D imaging with resolution down to 45 x 45 x 108 nm in a cell. The
      obtained results can be further improved by mathematical restoration algorithms.
      The far-field optical nanoscale resolution is attained in a variety of biological
      samples featuring strong variations in the local density of features.

PMID- 19772535
TI  - Application of edge detection method based on image quality gradient for twin
      detection.
AB  - An image quality based method was applied to quantitatively analyse the
      contribution of electrodeposited copper twinning. This method, based on the image
      quality as obtained from electron backscattering diffraction, involves three
      processes: hexagonal edge detection, thinning algorithm and twin determination.
      The twin density determined by the new algorithm was 65.61% which is higher than
      the twin density, 57.44% as determined by the Orientation Imaging Microscopy
      (OIM) analysis. The newly developed algorithm provides an alternative to twin
      boundary detection.

PMID- 19772536
TI  - Three-dimensional surface texture visualization of bone tissue through
      epifluorescence-based serial block face imaging.
AB  - Serial block face imaging is a microscopy technique in which the top of a
      specimen is cut or ground away and a mosaic of images is collected of the newly
      revealed cross-section. Images collected from each slice are then digitally
      stacked to achieve 3D images. The development of fully automated image
      acquisition devices has made serial block face imaging more attractive by greatly
      reducing labour requirements. The technique is particularly attractive for
      studies of biological activity within cancellous bone as it has the capability of
      achieving direct, automated measures of biological and morphological traits and
      their associations with one another. When used with fluorescence microscopy,
      serial block face imaging has the potential to achieve 3D images of tissue as
      well as fluorescent markers of biological activity. Epifluorescence-based serial
      block face imaging presents a number of unique challenges for visualizing bone
      specimens due to noise generated by sub-surface signal and local variations in
      tissue autofluorescence. Here we present techniques for processing serial block
      face images of trabecular bone using a combination of non-uniform illumination
      correction, precise tiling of the mosaic in each cross-section, cross-section
      alignment for vertical stacking, removal of sub-surface signal and segmentation.
      The resulting techniques allow examination of bone surface texture that will
      enable 3D quantitative measures of biological processes in cancellous bone
      biopsies.

PMID- 19772537
TI  - Estimation of variance components of local stereological volume estimators: a
      pilot study.
AB  - Local stereological techniques can be used for particle volume estimation based
      on information collected on a section plane through a reference point of the
      particle. We present methods for variability estimation of the local
      stereological volume estimators. This variability arises during the stereological
      estimation procedure and in the particle population. Both of these components can
      be estimated separately from planar sections. Our aim is to give a preliminary
      analysis of the possibility to include the particle structure interaction into
      the estimation procedure. For this reason, not only the section profiles, but
      also their locations, have to be recorded. The methods are applied for the
      sectional data obtained from neurons in the hippocampal brain region subiculum of
      four 3-month-old male Wistar rats. The proposed procedure enables one to obtain
      information about particle volume distribution.

PMID- 19772538
TI  - Automatic control of mechanical forces acting on cell biomembranes using a vision
      guided microrobotic system in computer microscopy.
AB  - A prototype for automatic control of mechanical forces acting on cell
      biomembranes is proposed in this paper. This prototype consists of vision-guided
      position control of the holder and micro-force sensor, automatic mechanical
      property characterization of cell biomembranes and automatic control of
      mechanical forces acting on cell biomembranes. A template-free calibration method
      and autofocusing of multiple objects are introduced in the vision-guided position
      control to minimize external biological contamination and position the cell,
      holder and micro-force sensor into the same focal plane, respectively. A third
      order polynomial modified from biomembrane point-load model describing the
      relationship between the measured mechanical force and the deformations of
      biomembranes is proposed. This simplified model is easily identified and inversed
      to facilitate the automatic control of mechanical forces. Experimental results
      based on zebrafish embryos demonstrate the feasibility of the proposed prototype.

PMID- 19772539
TI  - Two methods of random seed generation to avoid over-segmentation with stochastic
      watershed: application to nuclear fuel micrographs.
AB  - A stochastic version of the watershed algorithm is obtained by choosing randomly
      in the image the seeds from which the watershed regions are grown. The output of
      the procedure is a probability density function corresponding to the probability
      that each pixel belongs to a boundary. In the present paper, two stochastic seed
      generation processes are explored to avoid over-segmentation. The first is a non
      uniform Poisson process, the density of which is optimized on the basis of
      opening granulometry. The second process positions the seeds randomly within
      disks centred on the maxima of a distance map. The two methods are applied to
      characterize the grain structure of nuclear fuel pellets. Estimators are proposed
      for the total edge length and grain number per unit area, L(A) and N(A), which
      take advantage of the probabilistic nature of the probability density function
      and do not require segmentation.

PMID- 19772540
TI  - Pain medicine position paper.

PMID- 19772541
TI  - From the editors. Mining-related risks.

PMID- 19772542
TI  - Mining risks.

PMID- 19772545
TI  - Pneumonia in severely malnourished children in developing countries - mortality
      risk, aetiology and validity of WHO clinical signs: a systematic review.
AB  - OBJECTIVES: To quantify the degree by which moderate and severe degrees of
      malnutrition increase the mortality risk in pneumonia, to identify potential
      differences in the aetiology of pneumonia between children with and without
      severe malnutrition, and to evaluate the validity of WHO-recommended clinical
      signs (age-specific fast breathing and chest wall indrawing) for the diagnosis of
      pneumonia in severely malnourished children. METHODS: Systematic search of the
      existing literature using a variety of databases (Medline, EMBASE, the Web of
      Science, Scopus and CINAHL). RESULTS: Mortality risk: Sixteen relevant studies
      were identified, which universally showed that children with pneumonia and
      moderate or severe malnutrition are at higher risk of death. For severe
      malnutrition, reported relative risks ranged from 2.9 to 121.2; odds ratios
      ranged from 2.5 to 15.1. For moderate malnutrition, relative risks ranged from
      1.2 to 36.5. Aetiology: Eleven studies evaluated the aetiology of pneumonia in
      severely malnourished children. Commonly isolated bacterial pathogens were
      Klebsiella pneumoniae, Staphylococcus aureus, Streptococcus pneumoniae,
      Escherichia coli, and Haemophilus influenzae. The spectrum and frequency of
      organisms differed from those reported in children without severe malnutrition.
      There are very few data on the role of respiratory viruses and tuberculosis.
      Clinical signs: Four studies investigating the validity of clinical signs showed
      that WHO-recommended clinical signs were less sensitive as predictors of
      radiographic pneumonia in severely malnourished children. CONCLUSIONS: Pneumonia
      and malnutrition are two of the biggest killers in childhood. Guidelines for the
      care of children with pneumonia and malnutrition need to take into account this
      strong and often lethal association if they are to contribute to the UN
      Millennium Development Goal 4, aiming for substantial reductions in childhood
      mortality. Additional data regarding the optimal diagnostic approach to and
      management of pneumonia and malnutrition are required from regions where death
      from these two diseases is common.

PMID- 19772546
TI  - Impact of the shift from NCHS growth reference to WHO(2006) growth standards in a
      therapeutic feeding programme in Niger.
AB  - OBJECTIVES: To describe the implementation of the WHO(2006) growth standards in a
      therapeutic feeding programme. METHODS: Using programme monitoring data from
      21,769 children 6-59 months admitted to the Medecins Sans Frontieres therapeutic
      feeding programme during 2007, we compared characteristics at admission, type of
      care and outcomes for children admitted before and after the shift to the
      WHO(2006) standards. Admission criteria were bipedal oedema, MUAC <110 mm, or
      weight-for-height (WFH) of <-70% of the median (NCHS) before mid-May 2007, and
      WFH <-3 z score (WHO(2006)) after mid-May 2007. RESULTS: Children admitted with
      the WHO(2006) standards were more likely to be younger, with a higher proportion
      of males, and less malnourished (mean WFH -3.6 z score vs. mean WFH -4.6 z
      score). They were less likely to require hospitalization or intensive care
      (28.4%vs. 77%; 12.8%vs. 36.5%) and more likely to be treated exclusively on an
      outpatient basis (71.6%vs. 23%). Finally, they experienced better outcomes (cure
      rate: 89%vs. 71.7%, death rate: 2.7%vs. 6.4%, default rate: 6.7%vs. 12.3%).
      CONCLUSIONS: In this programme, the WHO(2006) standards identify a larger number
      of malnourished children at an earlier stage of disease facilitating their
      treatment success.

PMID- 19772547
TI  - Environmental, socio-demographic and behavioural determinants of malaria risk in
      the western Kenyan highlands: a case-control study.
AB  - OBJECTIVE: To identify risk factors for uncomplicated malaria in highland areas
      of East Africa at higher risk of malaria epidemics, in order to design
      appropriate interventions. METHODS: Prospective, population-based, case-control
      study in the Nandi Hills, a highland area of western Kenya, to identify
      environmental, sociodemographic and behavioural factors associated with clinical
      malaria. Data were collected using field observation, a structured questionnaire,
      and a global positioning system device. RESULTS: We interviewed 488 cases of
      slide-confirmed malaria and 980 age-matched controls. Multivariate analyses
      associated higher malaria risk with living <250 m of a forest [OR = 3.3 (95% CI
      1.5, 7.1)], <250 m of a swamp [2.8 (1.3, 5.9)], <200 m of maize fields [2.0 (1.2,
      3.4)], in the absence of trees <200 m [1.6 (1.2, 2.2)], on flat land [1.6 (1.2,
      2.2)], in houses without ceilings [1.5 (1.1, 2.2)], in houses with a separate
      kitchen building [1.8 (1.4, 2.3)] and in households where the female household
      head had no education [1.9 (1.1, 3.1)]. Travelling out of the study site [2.2
      (1.2, 4.1)] was also associated with increased risk. CONCLUSIONS; In this East
      African highland area, risk of developing uncomplicated malaria was
      multifactorial with a risk factor profile similar to that in endemic regions.
      Households within close proximity to forest and swamp borders are at higher risk
      of malaria and should be included in indoor residual spraying campaigns.

PMID- 19772548
TI  - Molecular assessment of Plasmodium falciparum resistance to antimalarial drugs in
      China.
AB  - OBJECTIVE: In China, Chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) were
      abandoned for the treatment of falciparum malaria 20 years ago due to resistance.
      Subsequent field studies showed a trend of declining CQ and SP resistance in the
      country. The main purpose of this study was to analyse the molecular markers of
      antimalarial resistance and thereby to assess the possibility of reintroduction
      of CQ or SP for falciparum malaria treatment. METHODS: Plasmodium falciparum
      field isolates were collected in 2006-2007 from Hainan and Yunnan provinces,
      China. Nested PCR-sequencing assays were applied to analyse the SNPs in four
      genes: P. falciparum chloroquine resistance transporter (pfcrt) gene, multi-drug
      resistance 1 (pfmdr1) gene, dihydrofolate reductase (dhfr) gene and
      dihydropteroate synthetase (dhps) gene. RESULTS: We found the widespread presence
      of point mutations in the dhfr and dhps genes which are associated with SP
      treatment failure. The molecular analyses also showed the fairly high prevalence
      of point mutation in the pfcrt gene which is linked to CQ resistance. CONCLUSION:
      The results of the present study indicate that CQ and SP should not be
      reintroduced for falciparum malaria treatment in the near future in China.

PMID- 19772549
TI  - Susceptibility to chemical insecticides of two Brazilian populations of the
      visceral leishmaniasis vector Lutzomyia longipalpis (Diptera: Psychodidae).
AB  - OBJECTIVES: To investigate the insecticide susceptibility of two geographically
      separated Lutzomyia longipalpis populations (Lapinha and Montes Claros) with
      different histories of insecticide exposure (i.e. no exposure and repeated
      exposure, respectively). METHODS: (i) Bioassay monitoring of sand fly survival
      over time when exposed to a range of insecticides; and (ii) analysis of the level
      of insecticide detoxification enzymes in individual sand flies caught at both
      study sites. Insecticides tested were the organophosphates malathion and
      fenitrothion and the pyrethroids lambda-cyhalothrin, permethrin and deltamethrin.
      RESULTS: Survival analyses showed that whilst there was no overall significant
      difference in susceptibility of both populations to organophosphates, Lapinha
      sand flies were significantly more susceptible to pyrethroids than those from
      Montes Claros. Multiple regression analyses also showed that insecticide
      susceptibility in both locations varied with sand fly sex. The relative
      susceptibilities of the two sand fly populations to tested insecticides were also
      compared. Thus, Montes Claros sand flies were most susceptible to malathion,
      followed by fenitrothion, deltamethrin and permethrin. Those from Lapinha were
      most susceptible to lambda-cyhalothrin, followed by malathion, permethrin,
      deltamethrin and fenitrothion. Biochemical analyses demonstrated that Montes
      Claros sand flies had significantly lower insecticide detoxification enzyme
      activity than Lapinha sand flies. CONCLUSIONS: Our results are the first record
      of significantly reduced susceptibility to the insecticides used in control of
      wild populations of Lu. longipalpis. They demonstrate the importance of
      evaluating chemicals against this species by conventional bioassay and microplate
      assays before and during spraying programmes.

PMID- 19772550
TI  - Epidemiology and prevention of human papillomavirus and cervical cancer in sub
      Saharan Africa: a comprehensive review.
AB  - OBJECTIVES: To identify the gaps of knowledge and highlight the challenges and
      opportunities for controlling cervical cancer in sub-Saharan Africa (SSA).
      METHODS: A comprehensive review of peer-reviewed literature to summarize the
      epidemiological data on human papillomavirus (HPV) and invasive cervical cancer
      (ICC) by HIV status, to review feasible and effective cervical screening
      strategies, and to identify barriers in the introduction of HPV vaccination in
      SSA. RESULTS: ICC incidence in SSA is one of the highest in the world with an age
      standardized incidence rate of 31.0 per 100,000 women. The prevalence of
      HPV16/18, the two vaccine preventable-types, among women with ICC, does not
      appear to differ by HIV status on a small case series. However, there are limited
      data on the role of HIV in the natural history of HPV infection in SSA. Cervical
      screening coverage ranges from 2.0% to 20.2% in urban areas and 0.4% to 14.0% in
      rural areas. There are few large scale initiatives to introduce population-based
      screening using cytology, visual inspection or HPV testing. Only one vaccine
      safety and immunogenicity study is being conducted in Senegal and Tanzania. Few
      data are available on vaccine acceptability, health systems preparedness and
      vaccine cost-effectiveness and long-term impact. CONCLUSIONS: Additional data are
      needed to strengthen ICC as a public health priority to introduce, implement and
      sustain effective cervical cancer control in Africa.

PMID- 19772551
TI  - Quality of medication use in primary care--mapping the problem, working to a
      solution: a systematic review of the literature.
AB  - BACKGROUND: The UK, USA and the World Health Organization have identified
      improved patient safety in healthcare as a priority. Medication error has been
      identified as one of the most frequent forms of medical error and is associated
      with significant medical harm. Errors are the result of the systems that produce
      them. In industrial settings, a range of systematic techniques have been designed
      to reduce error and waste. The first stage of these processes is to map out the
      whole system and its reliability at each stage. However, to date, studies of
      medication error and solutions have concentrated on individual parts of the whole
      system. In this paper we wished to conduct a systematic review of the literature,
      in order to map out the medication system with its associated errors and failures
      in quality, to assess the strength of the evidence and to use approaches from
      quality management to identify ways in which the system could be made safer.
      METHODS: We mapped out the medicines management system in primary care in the UK.
      We conducted a systematic literature review in order to refine our map of the
      system and to establish the quality of the research and reliability of the
      system. RESULTS: The map demonstrated that the proportion of errors in the
      management system for medicines in primary care is very high. Several stages of
      the process had error rates of 50% or more: repeat prescribing reviews, interface
      prescribing and communication and patient adherence. When including the efficacy
      of the medicine in the system, the available evidence suggested that only between
      4% and 21% of patients achieved the optimum benefit from their medication. Whilst
      there were some limitations in the evidence base, including the error rate
      measurement and the sampling strategies employed, there was sufficient
      information to indicate the ways in which the system could be improved, using
      management approaches. The first step to improving the overall quality would be
      routine monitoring of adherence, clinical effectiveness and hospital admissions.
      CONCLUSION: By adopting the whole system approach from a management perspective
      we have found where failures in quality occur in medication use in primary care
      in the UK, and where weaknesses occur in the associated evidence base. Quality
      management approaches have allowed us to develop a coherent change and research
      agenda in order to tackle these, so far, fairly intractable problems.

PMID- 19772552
TI  - Formulation of novel lipid-coated magnetic nanoparticles as the probe for in vivo
      imaging.
AB  - BACKGROUND: Application of superparamagnetic iron oxide nanoparticles (SPIOs) as
      the contrast agent has improved the quality of magnetic resonance (MR) imaging.
      Low efficiency of loading the commercially available iron oxide nanoparticles
      into cells and the cytotoxicity of previously formulated complexes limit their
      usage as the image probe. Here, we formulated new cationic lipid nanoparticles
      containing SPIOs feasible for in vivo imaging. METHODS: Hydrophobic SPIOs were
      incorporated into cationic lipid 1,2-dioleoyl-3-(trimethylammonium) propane
      (DOTAP) and polyethylene-glycol-2000-1,2-distearyl-3-sn-phosphatidylethanolamine
      (PEG-DSPE) based micelles by self-assembly procedure to form lipid-coated SPIOs
      (L-SPIOs). Trace amount of Rhodamine-dioleoyl-phosphatidylethanolamine (Rhodamine
      DOPE) was added as a fluorescent indicator. Particle size and zeta potential of L
      SPIOs were determined by Dynamic Light Scattering (DLS) and Laser Doppler
      Velocimetry (LDV), respectively. HeLa, PC-3 and Neuro-2a cells were tested for
      loading efficiency and cytotoxicity of L-SPIOs using fluorescent microscopy,
      Prussian blue staining and flow cytometry. L-SPIO-loaded CT-26 cells were tested
      for in vivo MR imaging. RESULTS: The novel formulation generates L-SPIOs particle
      with the average size of 46 nm. We showed efficient cellular uptake of these L
      SPIOs with cationic surface charge into HeLa, PC-3 and Neuro-2a cells. The L-SPIO
      loaded cells exhibited similar growth potential as compared to unloaded cells,
      and could be sorted by a magnet stand over ten-day duration. Furthermore, when
      SPIO-loaded CT-26 tumor cells were injected into Balb/c mice, the growth status
      of these tumor cells could be monitored using optical and MR images. CONCLUSION:
      We have developed a novel cationic lipid-based nanoparticle of SPIOs with high
      loading efficiency, low cytotoxicity and long-term imaging signals. The results
      suggested these newly formulated non-toxic lipid-coated magnetic nanoparticles as
      a versatile image probe for cell tracking.

PMID- 19772553
TI  - Competitive endothelial adhesion between Plasmodium falciparum isolates under
      physiological flow conditions.
AB  - BACKGROUND: Sequestration of parasitized red blood cells in the microvasculature
      of major organs involves a sequence of events that is believed to contribute to
      the pathogenesis of severe falciparum malaria. Plasmodium falciparum infections
      are commonly composed of multiple subpopulations of parasites with varied
      adhesive properties. A key question is: do these subpopulations compete for
      adhesion to endothelium? This study investigated whether, in a laboratory model
      of cytoadherence, there is competition in binding to endothelium between pRBC
      infected with P. falciparum of variant adhesive phenotypes, particularly under
      flow conditions. METHODS: Four different P. falciparum isolates, of known
      adherence phenotypes, were matched in pairs, mixed in different proportions and
      allowed to bind to cultured human endothelium. Using in vitro competitive static
      and flow-based adhesion assays, that allow simultaneous testing of the adhesive
      properties of two different parasite lines, adherence levels of paired P.
      falciparum isolates were quantified and analysed using either non-parametric
      Wilcoxon's paired signed rank test or Student paired test. RESULTS: Study
      findings show that P. falciparum parasite lines show marked differences in the
      efficiency of adhesion to endothelium. CONCLUSION: Plasmodium falciparum variants
      will compete for adhesion to endothelia and variants can be ranked by their
      efficiency of binding. These findings suggest that variants from a mixed
      infection will not show uniform cytoadherence and so may vary in their ability to
      cause disease.

PMID- 19772554
TI  - Interferon for the treatment of genital warts: a systematic review.
AB  - BACKGROUND: Interferon has been widely used in the treatment of genital warts for
      its immunomodulatory, antiproliferative and antiviral properties. Currently, no
      evidence that interferon improves the complete response rate or reduces the
      recurrence rate of genital warts has been generally provided. The aim of this
      review is to assess, from randomized control trials (RCTs), the efficacy and
      safety of interferon in curing genital warts. METHODS: We searched Cochrane
      Sexually Transmitted Diseases Group's Trials Register (January, 2009), Cochrane
      Central Register of Controlled Trials (2009, issue 1), PubMed (1950-2009), EMBASE
      (1974-2009), Chinese Biomedical Literature Database (CBM) (1975-2009), China
      National Knowledge Infrastructure (CNKI) (1979-2009), VIP database (1989-2009),
      as well as reference lists of relevant studies. Two reviewers independently
      screened searched studies, extracted data and evaluated their methodological
      qualities. RevMan 4.2.8 software was used for meta-analysis RESULTS: 12 RCTs
      involving 1445 people were included. Among them, 7 studies demonstrated the
      complete response rate of locally-used interferon as compared to placebo for
      treating genital warts. Based on meta-analysis, the rate of Complete response of
      the two interventions differed significantly (locally-used interferon:44.4%;
      placebo:16.1%). The difference between the two groups had statistical
      significance (RR 2.68, 95% CI 1.79 to 4.02, P < 0.00001). 5 studies demonstrated
      the complete response rate of systemically-used interferon as compared to placebo
      for treating genital warts. Based on meta-analysis, the rate of Complete response
      of the two interventions had no perceivable discrepancy (systemically-used
      interferon:27.4%; placebo:26.4%). The difference between the two groups had no
      statistical significance (RR1.25, 95% CI 0.80 to 1.95, P > 0.05). 7 studies
      demonstrated the recurrence rate of interferon as compared to placebo for
      treating genital warts. Based on meta-analysis, the recurrence rate of the two
      interventions had no perceivable discrepancy(interferon 21.1%; placebo: 34.2%).
      The difference between the two groups had no statistical significance (RR0.56,
      95% CI 0.27 to 1.18, P > 0.05). However, subgroup analysis showed that HPV
      infected patients with locally administered interferon were less likely than
      those given placebo to relapse, but that no significant difference in relapse
      rates was observed between systemic and placebo. The reported adverse events of
      interferon were mostly mild and transient, which could be well tolerated.
      CONCLUSION: Interferon tends to be a fairly well-tolerated form of therapy.
      According to different routes of administration, locally-used interferon appears
      to be much more effective than both systemically-used interferon and placebo in
      either improving the complete response rate or reducing the recurrence rate for
      the treatment of genital warts.

PMID- 19772555
TI  - Beyond literacy and numeracy in patient provider communication: focus groups
      suggest roles for empowerment, provider attitude and language.
AB  - BACKGROUND: Although the number of people living in the United States with
      limited English proficiency (LEP) is substantial, the impact of language on
      patients' experience of provider-patient communication has been little explored.
      METHODS: We conducted a series of 12 exploratory focus groups in English, Spanish
      and Cantonese to elicit discussion about patient-provider communication,
      particularly with respect to the concerns of the health literacy framework, i.e.
      ability to accurately understand, interpret and apply information given by
      providers. Within each language, 2 groups had high education and 2 had low
      education participants to partially account for literacy levels, which cannot be
      assessed consistently across three languages. Eighty-five (85) adults enrolled in
      the focus groups. The resulting video tapes were transcribed, translated and
      analyzed via content analysis. RESULTS: We identified 5 themes: 1) language
      discordant communication; 2) language concordant communication; 3) empowerment;
      4) providers' attitudes; 5) issues with the health care system. Despite efforts
      by facilitators to elicit responses related to cognitive understanding, issues of
      interpersonal process were more salient, and respondents did not readily separate
      issues of accurate understanding from their overall narratives of experience with
      health care and illness. Thematic codes often appeared to be associated with
      education level, language and/or culture. CONCLUSION: Our most salient finding
      was that for most of our participants there was no clear demarcation between
      literacy and numeracy, language interpretation, health communication,
      interpersonal relations with their provider and the rest of their experience with
      the health care system.

PMID- 19772556
TI  - The role of patient expectations in predicting outcome after total knee
      arthroplasty.
AB  - INTRODUCTION: Patient's expectations are variably reported to influence self
      rated outcome and satisfaction after medical treatment; this prospective study
      examined which of the following was the most important unique determinant of
      global outcome/satisfaction after total knee arthroplasty (TKA): baseline
      expectations; fulfillment of expectations; or current symptoms and function.
      METHODS: One hundred and twelve patients with osteoarthritis of the knee (age, 67
      +/- 9 years) completed a questionnaire about their expectations regarding months
      until full recovery, pain, and limitations in everyday activities after TKA
      surgery. Two years postoperatively, they were asked what the reality was for each
      of these domains, and rated the global outcome and satisfaction with surgery.
      Multivariable regression analyses using forward conditional selection of
      variables (and controlling for age, gender, other joint problems) identified the
      most significant determinants of outcome. RESULTS: Patients significantly
      underestimated the time for full recovery (expected 4.7 +/- 2.8 months, recalled
      actual time, 6.1 +/- 3.7 months; P = 0.005). They were also overly optimistic
      about the likelihood of being pain-free (85% expected it, 43% were; P < 0.05) and
      of not being limited in usual activities (52% expected it, 20% were; P < 0.05).
      Global outcomes were 46.2% excellent, 41.3% good, 10.6% fair and 1.9% poor. In
      multivariable regression, expectations did not make a significant unique
      contribution to explaining the variance in outcome/satisfaction; together with
      other joint problems, knee pain and function at 2 years postoperation predicted
      global outcome, and knee pain at 2 years predicted satisfaction. CONCLUSIONS: In
      this group, preoperative expectations of TKA surgery were overly optimistic. The
      routine analysis of patient-orientated outcomes in practice should assist the
      surgeon to convey more realistic expectations to the patient during the
      preoperative consultation. In multivariable regression, expectations did not
      predict global outcome/satisfaction; the most important determinants were other
      joint problems and the patient's pain and functional status 2 years
      postoperatively.

PMID- 19772557
TI  - BayesPeak: Bayesian analysis of ChIP-seq data.
AB  - BACKGROUND: High-throughput sequencing technology has become popular and widely
      used to study protein and DNA interactions. Chromatin immunoprecipitation,
      followed by sequencing of the resulting samples, produces large amounts of data
      that can be used to map genomic features such as transcription factor binding
      sites and histone modifications. METHODS: Our proposed statistical algorithm,
      BayesPeak, uses a fully Bayesian hidden Markov model to detect enriched locations
      in the genome. The structure accommodates the natural features of the
      Solexa/Illumina sequencing data and allows for overdispersion in the abundance of
      reads in different regions. Moreover, a control sample can be incorporated in the
      analysis to account for experimental and sequence biases. Markov chain Monte
      Carlo algorithms are applied to estimate the posterior distributions of the model
      parameters, and posterior probabilities are used to detect the sites of interest.
      CONCLUSION: We have presented a flexible approach for identifying peaks from ChIP
      seq reads, suitable for use on both transcription factor binding and histone
      modification data. Our method estimates probabilities of enrichment that can be
      used in downstream analysis. The method is assessed using experimentally verified
      data and is shown to provide high-confidence calls with low false positive rates.

PMID- 19772558
TI  - Paramedic clinical decision making during high acuity emergency calls: design and
      methodology of a Delphi study.
AB  - BACKGROUND: The scope of practice of paramedics in Canada has steadily evolved to
      include increasingly complex interventions in the prehospital setting, which
      likely have repercussions on clinical outcome and patient safety. Clinical
      decision making has been evaluated in several health professions, but there is a
      paucity of work in this area on paramedics. This study will utilize the Delphi
      technique to establish consensus on the most important instances of paramedic
      clinical decision making during high acuity emergency calls, as they relate to
      clinical outcome and patient safety. METHODS AND DESIGN: Participants in this
      multi-round survey study will be paramedic leaders and emergency medical services
      medical directors/physicians from across Canada. In the first round, participants
      will identify instances of clinical decision making they feel are important for
      patient outcome and safety. On the second round, the panel will rank each
      instance of clinical decision making in terms of its importance. On the third and
      potentially fourth round, participants will have the opportunity to revise the
      ranking they assigned to each instance of clinical decision making. Consensus
      will be considered achieved for the most important instances if 80% of the panel
      ranks it as important or extremely important. The most important instances of
      clinical decision making will be plotted on a process analysis map. DISCUSSION:
      The process analysis map that results from this Delphi study will enable the gaps
      in research, knowledge and practice to be identified.

PMID- 19772559
TI  - Proteome analysis of the Escherichia coli heat shock response under steady-state
      conditions.
AB  - In this study a proteomic approach was used to investigate the steady-state
      response of Escherichia coli to temperature up-shifts in a cascade of two
      continuously operated bioreactors. The first reactor served as cell source with
      optimal settings for microbial growth, while in the second chemostat the cells
      were exposed to elevated temperatures. By using this reactor configuration, which
      has not been reported to be used for the study of bacterial stress responses so
      far, it is possible to study temperature stress under well-defined, steady-state
      conditions. Specifically the effect on the cellular adaption to temperature
      stress using two-dimensional gel electrophoresis was examined and compared at the
      cultivation temperatures of 37 degrees C and 47.5 degrees C. As expected, the
      steady-state study with the double bioreactor configuration delivered a different
      protein spectrum compared to that obtained with standard batch experiments in
      shaking flasks and bioreactors. Setting a high cut-out spot-to-spot size ratio of
      5, proteins involved in defence against oxygen stress, functional cell envelope
      proteins, chaperones and proteins involved in protein biosynthesis, the energy
      metabolism and the amino acid biosynthesis were found to be differently expressed
      at high cultivation temperatures. The results demonstrate the complexity of the
      stress response in a steady-state culture not reported elsewhere to date.

PMID- 19772560
TI  - Pain patterns and descriptions in patients with radicular pain: does the pain
      necessarily follow a specific dermatome?
AB  - BACKGROUND: It is commonly stated that nerve root pain should be expected to
      follow a specific dermatome and that this information is useful to make the
      diagnosis of radiculopathy. There is little evidence in the literature that
      confirms or denies this statement. The purpose of this study is to describe and
      discuss the diagnostic utility of the distribution of pain in patients with
      cervical and lumbar radicular pain. METHODS: Pain drawings and descriptions were
      assessed in consecutive patients diagnosed with cervical or lumbar nerve root
      pain. These findings were compared with accepted dermatome maps to determine
      whether they tended to follow along the involved nerve root's dermatome. RESULTS:
      Two hundred twenty-six nerve roots in 169 patients were assessed. Overall, pain
      related to cervical nerve roots was non-dermatomal in over two-thirds (69.7%) of
      cases. In the lumbar spine, the pain was non-dermatomal in just under two-thirds
      (64.1%) of cases. The majority of nerve root levels involved non-dermatomal pain
      patterns except C4 (60.0% dermatomal) and S1 (64.9% dermatomal). The sensitivity
      (SE) and specificity (SP) for dermatomal pattern of pain are low for all nerve
      root levels with the exception of the C4 level (Se 0.60, Sp 0.72) and S1 level
      (Se 0.65, Sp 0.80), although in the case of the C4 level, the number of subjects
      was small (n = 5). CONCLUSION: In most cases nerve root pain should not be
      expected to follow along a specific dermatome, and a dermatomal distribution of
      pain is not a useful historical factor in the diagnosis of radicular pain. The
      possible exception to this is the S1 nerve root, in which the pain does commonly
      follow the S1 dermatome.

PMID- 19772561
TI  - Brain structure evolution in a basal vertebrate clade: evidence from phylogenetic
      comparative analysis of cichlid fishes.
AB  - BACKGROUND: The vertebrate brain is composed of several interconnected,
      functionally distinct structures and much debate has surrounded the basic
      question of how these structures evolve. On the one hand, according to the
      'mosaic evolution hypothesis', because of the elevated metabolic cost of brain
      tissue, selection is expected to target specific structures mediating the
      cognitive abilities which are being favored. On the other hand, the 'concerted
      evolution hypothesis' argues that developmental constraints limit such mosaic
      evolution and instead the size of the entire brain varies in response to
      selection on any of its constituent parts. To date, analyses of these hypotheses
      of brain evolution have been limited to mammals and birds; excluding
      Actinopterygii, the basal and most diverse class of vertebrates. Using a
      combination of recently developed phylogenetic multivariate allometry analyses
      and comparative methods that can identify distinct rates of evolution, even in
      highly correlated traits, we studied brain structure evolution in a highly
      variable clade of ray-finned fishes; the Tanganyikan cichlids. RESULTS: Total
      brain size explained 86% of the variance in brain structure volume in cichlids, a
      lower proportion than what has previously been reported for mammals. Brain
      structures showed variation in pair-wise allometry suggesting some degree of
      independence in evolutionary changes in size. This result is supported by
      variation among structures on the strength of their loadings on the principal
      size axis of the allometric analysis. The rate of evolution analyses generally
      supported the results of the multivariate allometry analyses, showing variation
      among several structures in their evolutionary patterns. The olfactory bulbs and
      hypothalamus were found to evolve faster than other structures while the dorsal
      medulla presented the slowest evolutionary rate. CONCLUSION: Our results favor a
      mosaic model of brain evolution, as certain structures are evolving in a modular
      fashion, with a small but non-negligible influence of concerted evolution in
      cichlid fishes. Interestingly, one of the structures presenting distinct
      evolutionary patterns within cichlids, the olfactory bulbs, has also been shown
      to evolve differently from other structures in mammals. Hence, our results for a
      basal vertebrate clade also point towards a conserved developmental plan for all
      vertebrates.

PMID- 19772562
TI  - Intraclonal mating occurs during tsetse transmission of Trypanosoma brucei.
AB  - BACKGROUND: Mating in Trypanosoma brucei is a non-obligatory event, triggered by
      the co-occurrence of different strains in the salivary glands of the vector.
      Recombinants that result from intra- rather than interclonal mating have been
      detected, but only in crosses of two different trypanosome strains. This has led
      to the hypothesis that when trypanosomes recognize a different strain, they
      release a diffusible factor or pheromone that triggers mating in any cell in the
      vicinity whether it is of the same or a different strain. This idea assumes that
      the trypanosome can recognize self and non-self, although there is as yet no
      evidence for the existence of mating types in T. brucei. RESULTS: We investigated
      intraclonal mating in T. b. brucei by crossing red and green fluorescent lines of
      a single strain, so that recombinant progeny can be detected in the fly by yellow
      fluorescence. For strain 1738, seven flies had both red and green trypanosomes in
      the salivary glands and, in three, yellow trypanosomes were also observed,
      although they could not be recovered for subsequent analysis. Nonetheless, both
      red and non-fluorescent clones from these flies had recombinant genotypes as
      judged by microsatellite and karyotype analyses, and some also had raised DNA
      contents, suggesting recombination or genome duplication. Strain J10 produced
      similar results indicative of intraclonal mating. In contrast, trypanosome clones
      recovered from other flies showed that genotypes can be transmitted with
      fidelity. When a yellow hybrid clone expressing both red and green fluorescent
      protein genes was transmitted, the salivary glands contained a mixture of
      fluorescent-coloured trypanosomes, but only yellow and red clones were recovered.
      While loss of the GFP gene in the red clones could have resulted from gene
      conversion, some of these clones showed loss of heterozygosity and raised DNA
      contents as in the other single strain transmissions. Our observations suggest
      that many recombinants are non-viable after intraclonal mating. CONCLUSION: We
      have demonstrated intraclonal mating during fly transmission of T. b. brucei,
      contrary to previous findings that recombination occurs only when another strain
      is present. It is thus no longer possible to assume that T. b. brucei remains
      genetically unaltered after fly transmission.

PMID- 19772563
TI  - Comparative evaluation of cell-free tumor DNA in blood and disseminated tumor
      cells in bone marrow of patients with primary breast cancer.
AB  - INTRODUCTION: The origin and clinical relevance of circulating cell-free tumor
      DNA in the blood of cancer patients is still unclear. Here we investigated
      whether the detection of this DNA is related to bone marrow (BM) micrometastasis
      and tumor recurrence in breast cancer patients. METHODS: BM aspirates of 81
      primary breast cancer patients were analyzed for the presence of disseminated
      tumor cells (DTC) by immunocytochemistry using the pan-cytokeratin antibody A45
      B/B3. PCR-based fluorescence microsatellite analysis was performed for detection
      of loss of heterozygosity (LOH) at 6 polymorphic markers using cell-free serum
      DNA. The data were correlated with established risk factors, and patients were
      followed-up over 6-10 years. RESULTS: LOH was detected in 33.5% of blood samples.
      The occurrence of LOH at the entire microsatellite marker set correlated with
      histopathology (P = 0.05) and grading (P = 0.006) of the primary tumor. The
      genomic region characterized by marker D9S171 was only affected by LOH in
      patients with increased tumor stages (pT2-4, P < 0.05) and older age (> or = 55
      years, P = 0.05). Kaplan-Meier analysis showed that LOH at D3S1255 (P = 0.009)
      and D9S171 (P = 0.001) were significantly associated with tumor relapse. In BM,
      DTC were detected in 39.5% of the patients, and this finding correlated with
      distant metastases (P < 0.05). Patients with DTC-positive BM had higher DNA
      yields in their blood than patients with DTC-negative BM (P < 0.05). However, no
      significant correlations were found between the presence of DTC in BM and the
      detection of marker-specific LOH on blood DNA. CONCLUSIONS: The detection of LOH
      on cell-free tumor DNA in blood is unrelated to BM micrometastasis and provides
      independent information on breast cancer progression.

PMID- 19772564
TI  - Efficacy of antibiotic therapy for SAPHO syndrome is lost after its
      discontinuation: an interventional study.
AB  - INTRODUCTION: The acronym SAPHO was introduced in 1987 to unify the various
      descriptions of a seronegative arthritis associated with skin manifestations and
      to show synovitis, acne, pustulosis, hyperostosis, and osteitis with and without
      sterile multifocal osteomyelitis. The etiology of SAPHO syndrome is unknown, but
      an association with infection by semipathogenic bacteria like Propionibacterium
      acnes has been suggested. We conducted an interventional study of SAPHO patients
      receiving antibiotics. METHODS: Thirty-seven patients met the clinical criteria
      of SAPHO syndrome, 21 of them underwent a needle biopsy of the osteitis lesion,
      and 14 of them showed positive bacteriological cultures for P. acnes. Thirty
      patients (14 bacteriological positive and 16 without biopsy) were treated with
      antibiotics for 16 weeks. The activity of skin disease and osteitis were assessed
      by a physician using a scoring model (from 0 to 6). In addition, patients
      completed a Health Assessment Score (HAS, from 0 to 6). The erythrocyte
      sedimentation rate was determined and a MRI (of the osteitis lesion, radiologic
      activity score from 0 to 2) was performed in week 1 (W1), week 16 (W16), and week
      28 (W28, 12 weeks after antibiotics). RESULTS: Twenty-seven patients continued
      the medication (azithromycin, n = 25, 500 mg twice a week; clindamycin, n = 1,
      300 mg daily; or doxycycline, n = 1, 100 mg daily) for 16 weeks. After W16 the
      scores for MRI (1.5 to 1.1, P = 0.01), skin activity (3.2 to 1.2, P = 0.01),
      osteitis activity (4.0 to 2.1, P = 0.02), and HAS (3.3 to 2.1, P = 0.01)
      decreased significantly. However, this was followed by increasing values for MRI
      scores (1.2 to 1.4, P = 0.08), skin activity (1.2 to 1.7, P = 0.11), osteitis
      activity (1.9 to 2.7, P = 0.01), and HAS (2.2 to 3.3, P = 0.02) from W16 to W28.
      The comparison of the scores in W1 and W28 in these 12 patients showed no
      significant differences. CONCLUSIONS: For the period of application, the
      antibiotic therapy seems to have controlled the disease. After antibiotic
      discontinuation, however, disease relapse was observed. SAPHO syndrome thus
      groups with other chronic inflammatory arthropathies with a need for permanent
      therapy.

PMID- 19772565
TI  - A method for determining the robustness of bio-molecular oscillator models.
AB  - BACKGROUND: Quantifying the robustness of biochemical models is important both
      for determining the validity of a natural system model and for designing reliable
      and robust synthetic biochemical networks. Several tools have been proposed in
      the literature. Unfortunately, multiparameter robustness analysis suffers from
      computational limitations. RESULTS: A novel method for quantifying the robustness
      of oscillatory behavior to parameter perturbations is presented in this paper.
      This method relies on the combination of Hopf bifurcation and Routh-Hurwitz
      stability criterion, which is widely applied in control system design. The
      proposed method is employed to calculate the robustness of two oscillating
      biochemical network models previously analyzed in the literature. The robustness
      bounds here obtained are tighter than what was previously obtained in the
      literature for both models. CONCLUSION: The method here proposed for quantifying
      the robustness of biochemical oscillator models is computationally less demanding
      than similar multiparamter variation techniques available in the literature. It
      also provides tighter bounds on two models previously analyzed in the literature.

PMID- 19772566
TI  - A comparison of reptilian and avian olfactory receptor gene repertoires: species
      specific expansion of group gamma genes in birds.
AB  - BACKGROUND: The detection of odorants is mediated by olfactory receptors (ORs).
      ORs are G-protein coupled receptors that form a remarkably large protein
      superfamily in vertebrate genomes. We used data that became available through
      recent sequencing efforts of reptilian and avian genomes to identify the complete
      OR gene repertoires in a lizard, the green anole (Anolis carolinensis), and in
      two birds, the chicken (Gallus gallus) and the zebra finch (Taeniopygia guttata).
      RESULTS: We identified 156 green anole OR genes, including 42 pseudogenes. The OR
      gene repertoire of the two bird species was substantially larger with 479 and 553
      OR gene homologs in the chicken and zebra finch, respectively (including 111 and
      221 pseudogenes, respectively). We show that the green anole has a higher
      fraction of intact OR genes (approximately 72%) compared with the chicken
      (approximately 66%) and the zebra finch (approximately 38%). We identified a
      larger number and a substantially higher proportion of intact OR gene homologs in
      the chicken genome than previously reported (214 versus 82 genes and 66% versus
      15%, respectively). Phylogenetic analysis showed that lizard and bird OR gene
      repertoires consist of group alpha, theta and gamma genes. Interestingly, the
      vast majority of the avian OR genes are confined to a large expansion of a single
      branch (the so called gamma-c clade). An analysis of the selective pressure on
      the paralogous genes of each gamma-c clade revealed that they have been subjected
      to adaptive evolution. This expansion appears to be bird-specific and not
      sauropsid-specific, as it is lacking from the lizard genome. The gamma-c
      expansions of the two birds do not intermix, i.e., they are lineage-specific.
      Almost all (group gamma-c) OR genes mapped to the unknown chromosome. The
      remaining OR genes mapped to six homologous chromosomes plus three to four
      additional chromosomes in the zebra finch and chicken. CONCLUSION: We identified
      a surprisingly large number of potentially functional avian OR genes. Our data
      supports recent evidence that avian olfactory ability may be better developed
      than previously thought. We hypothesize that the radiation of the group gamma-c
      OR genes in each bird lineage parallels the evolution of specific olfactory
      sensory functions.

PMID- 19772567
TI  - Donor site morbidity in oral mucosa graft urethroplasty: implications of tobacco
      consumption.
AB  - BACKGROUND: The purpose of this prospective study was to evaluate the donor site
      morbidity in patients who have undergone oral mucosa graft urethroplasty for
      stricture of the urethra. The impact of smoking and oral consumption of tobacco
      and/or paan masala on the donor site was also assessed. This study is probably
      the first of its kind where the affect of smoking, paan masala and tobacco
      chewing on the donor site morbidity has been documented. METHODS: Forty-eight
      patients suffering from stricture of the urethra underwent oral mucosa graft
      urethroplasty between July 2005 and December 2007. The patients were divided into
      two groups (users or non-users) based on tobacco consumption and oral hygiene.
      The donor site was evaluated at frequent intervals for pain, swelling, numbness,
      bleeding, salivation and tightness of mouth. RESULTS: Donor site morbidity was
      more in users with poor oral hygiene. Pain scores were higher amongst the users
      and the morbidity persisted longer in the users compared to non-users with good
      oral hygiene. CONCLUSION: Patients who consume tobacco and have poor oral hygiene
      should be warned regarding poorer outcomes after oral mucosa graft urethroplasty.

PMID- 19772568
TI  - Self-assessed bowel toxicity after external beam radiotherapy for prostate cancer
      -predictive factors on irritative symptoms, incontinence and rectal bleeding.
AB  - BACKGROUND: The aim of the study was to evaluate self-assessed bowel toxicity
      after radiotherapy (RT) for prostate cancer. In contrast to rectal bleeding,
      information concerning irritative symptoms (rectal urgency, pain) and
      incontinence after RT has not been adequately documented and reported in the
      past. METHODS: Patients (n = 286) have been surveyed prospectively before (A), at
      the last day (70.2-72.0 Gy; B), a median time of two (C) and 16 months after RT
      (D) using a validated questionnaire (Expanded Prostate Cancer Index Composite).
      Bowel domain score changes were analyzed and patient-/dose-volume-related factors
      tested for a predictive value on three separate factors (subscales): irritative
      symptoms, incontinence and rectal bleeding. RESULTS: Irritative symptoms were
      most strongly affected in the acute phase, but the scores of all subscales
      remained slightly lower at time D in comparison to baseline scores. Good
      correlations (correlation indices >0.4; p < 0.001 for all) were found between
      irritative and incontinence function/bother scores at times B-D, suggesting the
      presence of an urge incontinence for the majority of patients who reported
      uncontrolled leakage of stool. Planning target volume (PTV), haemorrhoids and
      stroke in past history were found to be independent predictive factors for rectal
      bleeding at time D. Chronic renal failure predisposed for lower irritative scores
      at time D. Paradoxically, patients with greater rectum volumes inside higher
      isodose levels presented with higher quality of life scores in the irritative and
      incontinence subscales. CONCLUSION: PTV and specific comorbidities are important
      predictive factors on adverse bowel quality of life changes after RT for prostate
      cancer. However, greater rectum volumes inside high isodose levels have not been
      found to be associated with lower quality of life scores.

PMID- 19772569
TI  - Inflammatory cytokines, goblet cell hyperplasia and altered lung mechanics in
      Lgl1+/- mice.
AB  - BACKGROUND: Neonatal lung injury, a leading cause of morbidity in prematurely
      born infants, has been associated with arrested alveolar development and is often
      accompanied by goblet cell hyperplasia. Genes that regulate alveolarization and
      inflammation are likely to contribute to susceptibility to neonatal lung injury.
      We previously cloned Lgl1, a developmentally regulated secreted glycoprotein in
      the lung. In rat, O2 toxicity caused reduced levels of Lgl1, which normalized
      during recovery. We report here on the generation of an Lgl1 knockout mouse in
      order to determine whether deficiency of Lgl1 is associated with arrested
      alveolarization and contributes to neonatal lung injury. METHODS: An Lgl1
      knockout mouse was generated by introduction of a neomycin cassette in exon 2 of
      the Lgl1 gene. To evaluate the pulmonary phenotype of Lgl1+/- mice, we assessed
      lung morphology, Lgl1 RNA and protein, elastin fibers and lung function. We also
      analyzed tracheal goblet cells, and expression of mucin, interleukin (IL)-4 and
      IL-13 as markers of inflammation. RESULTS: Absence of Lgl1 was lethal prior to
      lung formation. Postnatal Lgl1+/- lungs displayed delayed histological
      maturation, goblet cell hyperplasia, fragmented elastin fibers, and elevated
      expression of TH2 cytokines (IL-4 and IL-13). At one month of age, reduced
      expression of Lgl1 was associated with elevated tropoelastin expression and
      altered pulmonary mechanics. CONCLUSION: Our findings confirm that Lgl1 is
      essential for viability and is required for developmental processes that precede
      lung formation. Lgl1+/- mice display a complex phenotype characterized by delayed
      histological maturation, features of inflammation in the post-natal period and
      altered lung mechanics at maturity. Lgl1 haploinsufficiency may contribute to
      lung disease in prematurity and to increased risk for late-onset respiratory
      disease.

PMID- 19772570
TI  - Curricula for teaching the content of clinical practice guidelines to family
      medicine and internal medicine residents in the US: a survey study.
AB  - BACKGROUND: Teaching the content of clinical practice guidelines (CPGs) is
      important to both clinical care and graduate medical education. The objective of
      this study was to determine the characteristics of curricula for teaching the
      content of CPGs in family medicine and internal medicine residency programs in
      the United States. METHODS: We surveyed the directors of family medicine and
      internal medicine residency programs in the United States. The questionnaire
      included questions about the characteristics of the teaching of CPGs: goals and
      objectives, educational activities, evaluation, aspects of CPGs that the program
      teaches, the methods of making texts of CPGs available to residents, and the
      major barriers to teaching CPGs. RESULTS: Of 434 programs responding (out of 839,
      52%), 14% percent reported having written goals and objectives related to
      teaching CPGs. The most frequently taught aspect was the content of specific CPGs
      (76%). The top two educational strategies used were didactic sessions (76%) and
      journal clubs (64%). Auditing for adherence by residents was the primary
      evaluation strategy (44%), although 36% of program directors conducted no
      evaluation. Programs made texts of CPGs available to residents most commonly in
      the form of paper copies (54%) while the most important barrier was time
      constraints on faculty (56%). CONCLUSION: Residency programs teach different
      aspects of CPGs to varying degrees, and the majority uses educational strategies
      not supported by research evidence.

PMID- 19772571
TI  - Rationales, design and recruitment for the Elfe longitudinal study.
AB  - BACKGROUND: Many factors act simultaneously in childhood to influence health
      status, life chances and well being, including pre-birth influences, the
      environmental pollutants of early life, health status but also the social
      influences of family and school. A cohort study is needed to disentangle these
      influences and explore attribution. METHODS: Elfe will be a nationally
      representative cohort of 20 000 children followed from birth to adulthood using a
      multidisciplinary approach. The cohort will be based on the INSEE Permanent
      Demographic Panel (EDP) established using census data and civil records. The
      sample size has been defined in order to match the representativeness criteria
      and to obtain some prevalence estimation, but also to address the research area
      of low exposure/rare effects. The cohort will be based on repeated surveys by
      face to face or phone interview (at birth and each year) as well as medical
      interview (at 2 years) and examination (at 6 years). Furthermore, biological
      samples will be taken at birth to evaluate the foetal exposition to toxic
      substances, environmental sensors will be placed in the child's homes. Pilot
      studies have been initiated in 2007 (500 children) with an overall acceptance
      rate of 55% and are currently under progress, the 2-year survey being carried out
      in October this year. DISCUSSION: The longitudinal study will provide a unique
      source of data to analyse the development of children in their environment, to
      study the various factors interacting throughout the life course up to adulthood
      and to determine the impact of childhood experience on the individual's physical,
      psychological, social and professional development.

PMID- 19772572
TI  - The capacity for multistability in small gene regulatory networks.
AB  - BACKGROUND: Recent years have seen a dramatic increase in the use of mathematical
      modeling to gain insight into gene regulatory network behavior across many
      different organisms. In particular, there has been considerable interest in using
      mathematical tools to understand how multistable regulatory networks may
      contribute to developmental processes such as cell fate determination. Indeed,
      such a network may subserve the formation of unicellular leaf hairs (trichomes)
      in the model plant Arabidopsis thaliana. RESULTS: In order to investigate the
      capacity of small gene regulatory networks to generate multiple equilibria, we
      present a chemical reaction network (CRN)-based modeling formalism and describe a
      number of methods for CRN analysis in a parameter-free context. These methods are
      compared and applied to a full set of one-component subnetworks, as well as a
      large random sample from 40,680 similarly constructed two-component subnetworks.
      We find that positive feedback and cooperativity mediated by transcription factor
      (TF) dimerization is a requirement for one-component subnetwork bistability. For
      subnetworks with two components, the presence of these processes increases the
      probability that a randomly sampled subnetwork will exhibit multiple equilibria,
      although we find several examples of bistable two-component subnetworks that do
      not involve cooperative TF-promoter binding. In the specific case of epidermal
      differentiation in Arabidopsis, dimerization of the GL3-GL1 complex and
      cooperative sequential binding of GL3-GL1 to the CPC promoter are each
      independently sufficient for bistability. CONCLUSION: Computational methods
      utilizing CRN-specific theorems to rule out bistability in small gene regulatory
      networks are far superior to techniques generally applicable to deterministic ODE
      systems. Using these methods to conduct an unbiased survey of parameter-free
      deterministic models of small networks, and the Arabidopsis epidermal cell
      differentiation subnetwork in particular, we illustrate how future experimental
      research may be guided by network structure analysis.

PMID- 19772573
TI  - Incorporating multiple interventions in meta-analysis: an evaluation of the mixed
      treatment comparison with the adjusted indirect comparison.
AB  - BACKGROUND: Comparing the effectiveness of interventions is now a requirement for
      regulatory approval in several countries. It also aids in clinical and public
      health decision-making. However, in the absence of head-to-head randomized trials
      (RCTs), determining the relative effectiveness of interventions is challenging.
      Several methodological options are now available. We aimed to determine the
      comparative validity of the adjusted indirect comparisons of RCTs with the mixed
      treatment comparison approach. METHODS: Using systematic searching, we identified
      all meta-analyses evaluating more than 3 interventions for a similar disease
      state with binary outcomes. We abstracted data on each clinical trial including
      population n and outcomes. We conducted fixed effects meta-analysis of each
      intervention versus mutual comparator and then applied the adjusted indirect
      comparison. We conducted a mixed treatment meta-analysis on all trials and
      compared the point estimates and 95% confidence/credible intervals (CIs/CrIs) to
      determine important differences. RESULTS: We included data from 7 reviews that
      met our inclusion criteria, allowing a total of 51 comparisons. According to the
      a priori consistency rule, we found 2 examples where the analytic comparisons
      were statistically significant using the mixed treatment comparison over the
      adjusted indirect comparisons and 1 example where this was vice versa. We found 6
      examples where the direction of effect differed according to the indirect
      comparison method chosen and we found 9 examples where the confidence intervals
      were importantly different between approaches. CONCLUSION: In most analyses, the
      adjusted indirect comparison yields estimates of relative effectiveness equal to
      the mixed treatment comparison. In less complex indirect comparisons, where all
      studies share a mutual comparator, both approaches yield similar benefits. As
      comparisons become more complex, the mixed treatment comparison may be favoured.

PMID- 19772574
TI  - Depressive symptoms from kindergarten to early school age: longitudinal
      associations with social skills deficits and peer victimization.
AB  - BACKGROUND: Depressive symptoms in children are associated with social skills
      deficits and problems with peers. We propose a model which suggests different
      mechanisms for the impact of deficits in self-oriented social skills
      (assertiveness and social participation) and other-oriented social skills (pro
      social, cooperative and non-aggressive behaviors) on children's depressive
      symptoms. We hypothesized that deficits in self-oriented social skills have a
      direct impact on children's depressive symptoms because these children have non
      rewarding interactions with peers, whereas the impact of deficits in other
      oriented social skills on depressive symptoms is mediated through negative
      reactions from peers such as peer victimization. METHOD: 378 kindergarten
      children (163 girls) participated at two assessments (Age at T1: M = 5.8, T2: M =
      7.4). Teachers completed questionnaires on children's social skills at T1.
      Teacher reports on peer victimization and depressive symptoms were assessed at
      both assessment points. RESULTS: Our study partially confirmed the suggested
      conceptual model. Deficits in self-oriented social skills significantly predicted
      depressive symptoms, whereas deficits in other-oriented social skills were more
      strongly associated with peer victimization. Longitudinal associations between
      other-oriented social skills and depressive symptoms were mediated through peer
      victimization. CONCLUSION: The study emphasizes the role of deficits in self
      oriented social skills and peer victimization for the development of
      internalizing disorders.

PMID- 19772575
TI  - Distinct changes in soybean xylem sap proteome in response to pathogenic and
      symbiotic microbe interactions.
AB  - BACKGROUND: Plant systemic signaling characterized by the long distance transport
      of molecules across plant organs involves the xylem and phloem conduits. Root
      microbe interactions generate systemic signals that are transported to aerial
      organs via the xylem sap. We analyzed the xylem sap proteome of soybean seedlings
      in response to pathogenic and symbiotic interactions to identify systemic
      signaling proteins and other differentially expressed proteins. RESULTS: We
      observed the increase of a serine protease and peroxidase in the xylem sap in
      response to Phytophthora sojae elicitor treatment. The high molecular weight
      fraction of soybean xylem sap was found to promote the growth of Neurospora
      crassa in vitro at lower concentrations and inhibit growth at higher
      concentrations. Sap from soybean plants treated with a P. sojae elicitor had a
      significantly higher inhibitory effect than sap from control soybean plants. When
      soybean seedlings were inoculated with the symbiont Bradyrhizobium japonicum, the
      abundance of a xyloglucan transendoglycosyl transferase protein increased in the
      xylem sap. However, RNAi-mediated silencing of the corresponding gene did not
      significantly affect nodulation in soybean hairy root composite plants.
      CONCLUSION: Our study identified a number of sap proteins from soybean that are
      differentially induced in response to B. japonicum and P. sojae elicitor
      treatments and a majority of them were secreted proteins.

PMID- 19772576
TI  - Association between leukocyte telomere shortening and exposure to traffic
      pollution: a cross-sectional study on traffic officers and indoor office workers.
AB  - BACKGROUND: Telomere shortening in blood leukocytes has been associated with
      increased morbidity and death from cardiovascular disease and cancer, but
      determinants of shortened telomeres, a molecular feature of biological aging, are
      still largely unidentified. Traffic pollution has been linked with both
      cardiovascular and cancer risks, particularly in older subjects. Whether exposure
      to traffic pollution is associated with telomere shortening has never been
      evaluated. METHODS: We measured leukocyte telomere length (LTL) by real-time PCR
      in blood DNA from 77 traffic officers exposed to high levels of traffic
      pollutants and 57 office workers (referents). Airborne benzene and toluene, as
      tracers for traffic exposure, were measured using personal passive samplers and
      gas-chromatography/flame-ionization detector analysis. We used covariate-adjusted
      multivariable models to test the effects of the exposure on LTL and obtain
      adjusted LTL means and 95% Confidence Intervals (CIs). RESULTS: Adjusted mean LTL
      was 1.10 (95%CI 1.04-1.16) in traffic officers and 1.27 in referents (95%CI 1.20
      1.35) [p < 0.001]. LTL decreased in association with age in both traffic officers
      (p = 0.01) and referents (p = 0.001), but traffic officers had shorter LTL within
      each age category. Among traffic officers, adjusted mean relative LTL was shorter
      in individuals working in high (n = 45, LTL = 1.02, 95%CI 0.96-1.09) compared to
      low traffic intensity (n = 32, LTL = 1.22, 95%CI 1.13-1.31) [p < 0.001]. In the
      entire study population, LTL decreased with increasing levels of personal
      exposure to benzene (p = 0.004) and toluene (p = 0.008). CONCLUSION: Our results
      indicate that leukocyte telomere length is shortened in subjects exposed to
      traffic pollution, suggesting evidence of early biological aging and disease
      risk.

PMID- 19772577
TI  - Inversion 2La is associated with enhanced desiccation resistance in Anopheles
      gambiae.
AB  - BACKGROUND: Anopheles gambiae, the principal vector of malignant malaria in
      Africa, occupies a wide range of habitats. Environmental flexibility may be
      conferred by a number of chromosomal inversions non-randomly associated with
      aridity, including 2La. The purpose of this study was to determine the
      physiological mechanisms associated with the 2La inversion that may result in the
      preferential survival of its carriers in hygrically-stressful environments.
      METHODS: Two homokaryotypic populations of A. gambiae (inverted 2La and standard
      2L+(a)) were created from a parental laboratory colony polymorphic for 2La and
      standard for all other known inversions. Desiccation resistance, water, energy
      and dry mass of adult females of both populations were compared at several ages
      and following acclimation to a more arid environment. RESULTS: Females carrying
      2La were significantly more resistant to desiccation than 2L+(a) females at
      emergence and four days post-emergence, for different reasons. Teneral 2La
      females had lower rates of water loss than their 2L+(a) counterparts, while at
      four days, 2La females had higher initial water content. No differences in
      desiccation resistance were found at eight days, with or without acclimation.
      However, acclimation resulted in both populations significantly reducing their
      rates of water loss and increasing their desiccation resistance. Acclimation had
      contrasting effects on the body characteristics of the two populations: 2La
      females boosted their glycogen stores and decreased lipids, whereas 2La females
      did the contrary. CONCLUSION: Variation in rates of water loss and response to
      acclimation are associated with alternative arrangements of the 2La inversion.
      Understanding the mechanisms underlying these traits will help explain how
      inversion polymorphisms permit exploitation of a heterogeneous environment by
      this disease vector.

PMID- 19772578
TI  - Two-stage case-control association study of dopamine-related genes and migraine.
AB  - BACKGROUND: We previously reported risk haplotypes for two genes related with
      serotonin and dopamine metabolism: MAOA in migraine without aura and DDC in
      migraine with aura. Herein we investigate the contribution to migraine
      susceptibility of eight additional genes involved in dopamine neurotransmission.
      METHODS: We performed a two-stage case-control association study of 50 tag single
      nucleotide polymorphisms (SNPs), selected according to genetic coverage
      parameters. The first analysis consisted of 263 patients and 274 controls and the
      replication study was composed by 259 cases and 287 controls. All cases were
      diagnosed according to ICHD-II criteria, were Spanish Caucasian, and were sex
      matched with control subjects. RESULTS: Single-marker analysis of the first
      population identified nominal associations of five genes with migraine. After
      applying a false discovery rate correction of 10%, the differences remained
      significant only for DRD2 (rs2283265) and TH (rs2070762). Multiple-marker
      analysis identified a five-marker T-C-G-C-G (rs12363125-rs2283265-rs2242592
      rs1554929-rs2234689) risk haplotype in DRD2 and a two-marker A-C (rs6356
      rs2070762) risk haplotype in TH that remained significant after correction by
      permutations. These results, however, were not replicated in the second
      independent cohort. CONCLUSION: The present study does not support the
      involvement of the DRD1, DRD2, DRD3, DRD5, DBH, COMT, SLC6A3 and TH genes in the
      genetic predisposition to migraine in the Spanish population.

PMID- 19772579
TI  - Bisphosphonates and atrial fibrillation: Bayesian meta-analyses of randomized
      controlled trials and observational studies.
AB  - BACKGROUND: Occurrence of atrial fibrillation (AF) amongst bisphosphonate users
      has been increasingly reported but results are conflicting. We performed a
      Bayesian meta-analysis to address the possible association between the occurrence
      of AF and bisphosphonate use and estimated the posterior probability of
      development of AF with bisphosphonate use. METHODS: Randomized controlled trials
      (RCTs) evaluating the efficacy and safety of bisphosphonates for treating and
      preventing osteoporosis, and observational studies investigating the incidence of
      AF amongst bisphosphonate users, were searched in electronic databases. We pooled
      the effect size with Bayesian meta-analysis for odds ratio (OR) and calculated
      its posterior probability of development of AF in bisphosphonate users for RCTs
      and observational studies, reported with the 95% credible interval (CI). RESULTS:
      Of 1751 potentially relevant citations initially retrieved, 4 RCTs and 2 reports
      of RCTs, and 3 observational studies were included for this meta-analysis. On
      pooling the RCTs, there was a non-significantly higher risk of overall (OR 1.184,
      95% CI 0.837-1.656) and serious AF (OR 1.590, 95% CI 0.613-3.751) in
      bisphosphonate-treated patients. Combining data of observational studies also
      revealed a non-significantly higher risk of AF in bisphosphonate users (OR 1.251,
      95% CI 0.980-1.732). Using Bayesian meta-analysis based on the effect size of
      observational studies as the prior, the posterior probability of OR>1.2 in the
      development of AF amongst bisphosphonate users in the RCTs was 0.484. Egger's
      regression demonstrated no notable publication bias in all the analyses.
      CONCLUSION: The current meta-analysis revealed no evidence of a higher risk of AF
      associated with bisphosphonate use. Nevertheless, based on Bayesian meta-analysis
      with the effect size of the observational studies as the prior, the posterior
      probabilities of development of AF was found to be 0.484 if the risk of AF was
      estimated to be more than 20%. The results of the current meta-analysis thus
      offer clinicians the practical probability of development of AF in patients who
      take bisphosphonates for the treatment of bone loss and corticosteroid induced
      osteoporosis.

PMID- 19772580
TI  - Biofilm formation as a novel phenotypic feature of adherent-invasive Escherichia
      coli (AIEC).
AB  - BACKGROUND: Crohn's disease (CD) is a high morbidity chronic inflammatory
      disorder of unknown aetiology. Adherent-invasive Escherichia coli (AIEC) has been
      recently implicated in the origin and perpetuation of CD. Because bacterial
      biofilms in the gut mucosa are suspected to play a role in CD and biofilm
      formation is a feature of certain pathogenic E. coli strains, we compared the
      biofilm formation capacity of 27 AIEC and 38 non-AIEC strains isolated from the
      intestinal mucosa. Biofilm formation capacity was then contrasted with the AIEC
      phenotype, the serotype, the phylotype, and the presence of virulence genes.
      RESULTS: Specific biofilm formation (SBF) indices were higher amongst AIEC than
      non-AIEC strains (P = 0.012). In addition, 65.4% of moderate to strong biofilms
      producers were AIEC, whereas 74.4% of weak biofilm producers were non-AIEC (P =
      0.002). These data indicate that AIEC strains were more efficient biofilm
      producers than non-AIEC strains. Moreover, adhesion (P = 0.009) and invasion (P =
      0.003) indices correlated positively with higher SBF indices. Additionally,
      motility (100%, P < 0.001), H1 type flagellin (53.8%, P < 0.001), serogroups O83
      (19.2%, P = 0.008) and O22 (26.9%, P = 0.001), the presence of virulence genes
      such as sfa/focDE (38.5%, P = 0.003) and ibeA (26.9%, P = 0.017), and B2
      phylotype (80.8%, P < 0.001) were frequent characteristics amongst biofilm
      producers. CONCLUSION: The principal contribution of the present work is the
      finding that biofilm formation capacity is a novel, complementary pathogenic
      feature of the recently described AIEC pathovar. Characterization of AIEC
      specific genetic determinants, and the regulatory pathways, involved in biofilm
      formation will likely bring new insights into AIEC pathogenesis.

PMID- 19772581
TI  - Association of the TLR4 Asp299Gly polymorphism with lung function in relation to
      body mass index.
AB  - BACKGROUND: Previous studies have shown conflicting results for the association
      between TLR4 polymorphism (Asp299Gly) and lung function. We investigated the
      influence of TLR4 Asp299Gly, a polymorphism, on lung function in a community
      population. METHODS: In 2003, a cross-sectional survey was conducted to assess
      the respiratory health of residents living in and around the town of Humboldt,
      Saskatchewan, Canada. There were 2090 adults age 18-79 years who completed a
      questionnaire that included a medical and smoking history, as well as socio
      economic and lifestyle variables. Genetic information and lung function test
      measurements were available on 1725 subjects (754 males and 971 females) of the
      2090 respondents. These subjects were selected for further analysis to
      investigate the association between TLR4 Asp299Gly genotype and forced expiratory
      volume in the first second in liters (FEV1), forced vital capacity in liters
      (FVC), FEV1/FVC ratio, and forced expiratory flow rate in liters/second (FEF25
      75). Multivariable linear regression analysis was used to investigate
      associations. RESULTS: Adjusted mean values of FEV1 and FVC were significantly
      different between TLR4 wild type and TLR4 variant groups [Mean +/- S.E.: (TLR4
      wild type - FEV1: 3.18 +/- 0.02, FVC: 3.95 +/- 0.03; TLR4 variant - FEV1: 3.31 +/
      0.06, FVC: 4.14 +/- 0.07)]. Based on multivariable regression analysis, we
      observed that body mass index (BMI) was associated with decreased FEV1/FVC ratio
      and FEF25-75 in TLR4 variant group but not in wild type group. CONCLUSION: BMI
      may modify the associations of TLR4 Asp299Gly polymorphism with FEV1/FVC ratio
      and FEF25-75.

PMID- 19772582
TI  - In their own words: qualitative study of high-utilising primary care patients
      with medically unexplained symptoms.
AB  - BACKGROUND: High utilising primary care patients with medically unexplained
      symptoms (MUS) often frustrate their primary care providers. Studies that
      elucidate the attitudes of these patients may help to increase understanding and
      improve confidence of clinicians who care for them. The objective of this study
      was to describe and analyze perceptions and lived experiences of high utilising
      primary care patients with MUS. METHODS: A purposive sample of 19 high utilising
      primary care patients for whom at least 50% (69.6% in this sample) of visits for
      two years could not be explained medically, were encouraged to talk spontaneously
      about themselves and answer semi-structured questions. Verbatim transcripts of
      interviews were analyzed using an iterative consensus building process. RESULTS:
      Patients with MUS almost universally described current and/or past family
      dysfunction and were subjected to excessive testing and ineffective empirical
      treatments. Three distinct groups emerged from the data. 1) Some patients, who
      had achieved a significant degree of psychological insight and had success in
      life, primarily sought explanations for their symptoms. 2) Patients who had less
      psychological insight were more disabled by their symptoms and felt strongly
      entitled to be excused from normal social obligations. Typically, these patients
      primarily sought symptom relief, legitimization, and support. 3) Patients who
      expressed worry about missed diagnoses demanded excessive care and complained
      when their demands were resisted. CONCLUSION: High utilising primary care
      patients are a heterogeneous group with similar experiences and different
      perceptions, behaviours and needs. Recognizing these differences may be critical
      to effective treatment and reduction in utilisation.

PMID- 19772583
TI  - Characteristics of patients with chronic back pain who benefit from acupuncture.
AB  - BACKGROUND: Although many clinicians believe there are clinically important
      subgroups of persons with "non-specific" low back pain, such subgroups have not
      yet been clearly identified. As part of a large trial evaluating acupuncture for
      chronic low back pain, we sought to identify subgroups of participants that were
      particularly responsive to acupuncture. METHODS: We performed a secondary
      analysis of data for the 638 participants in our clinical trial comparing
      different types of acupuncture to usual care to identify baseline characteristics
      that predicted responses to individualized, standardized, or simulated
      acupuncture treatments. After identifying factors that predicted improvements in
      back-related function or symptoms, we determined if these factors were more
      likely to predict improvement for those receiving the acupuncture treatments than
      for those receiving usual care. This was accomplished by testing for an
      interaction between the prognostic factors and treatment group in four models:
      functional outcomes (measured by the Roland-Morris Disability Scale) at 8 and 52
      weeks post-randomization and symptom outcomes (measured with a numerical rating
      scale) at 8 and 52 weeks. RESULTS: Overall, the strongest predictors of
      improvement in back function and symptoms were higher baseline levels of these
      measures, receipt of an acupuncture treatment, and non-use of narcotic
      analgesics. Benefit from acupuncture compared to usual care was greater with
      worse pre-treatment levels of back dysfunction (interaction p < 0.004 for the
      functional outcome, Roland Morris Disability Scale at 8 weeks). No other
      consistent interactions were observed. CONCLUSION: This secondary analysis found
      little evidence for the existence of subgroups of patients with chronic back pain
      that would be especially likely to benefit from acupuncture. However, persons
      with chronic low back pain who had more severe baseline dysfunction had the most
      short-term benefit from acupuncture.

PMID- 19772584
TI  - Genetic variation for body weight change in mice in response to physical
      exercise.
AB  - BACKGROUND: Physical activity is beneficial in reducing the weight gain and
      associated health problems often experienced by individuals as they age, but the
      association of weight change with physical activity remains complex. We tested
      for a possible genetic basis for this association between 9-12-week body weight
      change (WTC) and the distance, duration, and speed voluntarily run by 307 mice in
      an F2 population produced from an intercross of two inbred strains (C57L/J and
      C3H/HeJ) that differed dramatically in their physical activity levels. RESULTS:
      In this population WTC did show the expected negative association with the
      physical activity traits, but only the phenotypic correlation of WTC with speed (
      0.18) reached statistical significance. Using an interval mapping approach with
      single-nucleotide polymorphism markers, we discovered five (four suggestive and
      one significant) quantitative trait loci (QTLs) affecting body weight change,
      only one of which appeared to show pleiotropic effects on the physical activity
      traits as well. Genome-wide epistasis scans also detected several pairwise
      interactions of QTLs with pleiotropic effects on WTC and the physical activity
      traits, but these effects made a significant contribution (51%) only to the
      covariance of WTC with speed. CONCLUSION: It was concluded that the genetic
      contribution to the phenotypic association between WTC and the physical activity
      traits in this population of mice was primarily epistatic in origin, restricted
      to one measure of physical activity, and could be quite variable among different
      populations depending on the genetic background, experimental design and traits
      assessed.

PMID- 19772585
TI  - Control of CD56 expression and tumor cell cytotoxicity in human Vgamma2Vdelta2 T
      cells.
AB  - BACKGROUND: In lymphocyte subsets, expression of CD56 (neural cell adhesion
      molecule-1) correlates with cytotoxic effector activity. For cells bearing the
      Vgamma2Vdelta2 T cell receptor, isoprenoid pyrophosphate stimulation leads to
      uniform activation and proliferation, but only a fraction of cells express CD56
      and display potent cytotoxic activity against tumor cells. Our goal was to show
      whether CD56 expression was regulated stochastically, similar to conventional
      activation antigens, or whether CD56 defined a lineage of cells committed to the
      cytotoxic phenotype. RESULTS: Tracking individual cell clones defined by their
      Vgamma2 chain CDR3 region sequences, we found that CD56 was expressed on
      precursor cytotoxic T cells already present in the population irrespective of
      their capacity to proliferate after antigen stimulation. Public T cell receptor
      sequences found in the CD56+ subset from one individual might appear in the CD56-
      subset of another donor. The commitment of individual clones to CD56+ or CD56-
      lineages was stable for each donor over a 1 year interval. CONCLUSION: The
      ability to express CD56 was not predicted by TCR sequence or by the strength of
      signal received by the TCR. For gammadelta T cells, cytotoxic effector function
      is acquired when cytotoxic precursors within the population are stimulated to
      proliferate and express CD56. Expression of CD56 defines a committed lineage to
      the cytotoxic phenotype.

PMID- 19772586
TI  - Procalcitonin levels and bacterial aetiology among COPD patients admitted to the
      ICU with severe pneumonia: a prospective cohort study.
AB  - BACKGROUND: Serum procalcitonin (PCT) is considered useful in predicting the
      likeliness of developing bacterial infections in emergency setting. In this
      study, we describe PCT levels overtime and their relationship with bacterial
      infection in chronic obstructive pulmonary disease (COPD) critically ill patients
      with pneumonia. METHODS: We conducted a prospective cohort study in an ICU of a
      University Hospital. All consecutive COPD patients admitted for pneumonia between
      September 2005 and September 2006 were included. Respiratory samples were tested
      for the presence of bacteria and viruses. Procalcitonin was sequentially assessed
      and patients classified according to the probability of the presence of a
      bacterial infection. RESULTS: Thirty four patients were included. The PCT levels
      were assessed in 32/34 patients, median values were: 0.493 microg/L [IQR, 0.131
      to 1.471] at the time of admission, 0.724 microg/L [IQR, 0.167 to 2.646] at six
      hours, and 0.557 microg/L [IQR, 0.123 to 3.4] at 24 hours. The highest PCT
      (PCTmax) levels were less than 0.1 microg/L in 3/32 (9%) patients and greater
      than 0.25 microg/L in 22/32 (69%) patients, suggesting low and high probability
      of bacterial infection, respectively. Fifteen bacteria and five viruses were
      detected in 15/34 (44%) patients. Bacteria were not detected in patients with
      PCTmax levels < 0.1 microg/L. In contrast, bacteria were detected in 4/7 (57%)
      patients estimated unlikely to have a bacterial infection by PCT levels (PCTmax >
      0.1 and < 0.25 microg/L). CONCLUSION: Based on these results we suggest that a
      PCT level cut off > 0.1 microg/L may be more appropriate than 0.25 microg/L
      (previously proposed for non severe lower respiratory tract infection) to predict
      the probability of a bacterial infection in severe COPD patients with pneumonia.
      Further studies testing procalcitonin-based antibiotic strategies are needed in
      COPD patients with severe pneumonia.

PMID- 19772587
TI  - Prognostic value of adenosine stress cardiovascular magnetic resonance in
      patients with low-risk chest pain.
AB  - BACKGROUND: Approximately 5% of patients with an acute coronary syndrome are
      discharged from the emergency room with an erroneous diagnosis of non-cardiac
      chest pain. Highly accurate non-invasive stress imaging is valuable for
      assessment of low-risk chest pain patients to prevent these errors. Adenosine
      stress cardiovascular magnetic resonance (AS-CMR) is an imaging modality with
      increasing application. The goal of this study was to evaluate the negative
      prognostic value of AS-CMR among low-risk acute chest pain patients. METHODS: We
      studied 103 patients, mean 56.7 + or - 12.3 years of age, with chest pain and no
      electrocardiographic evidence of ischemia and negative cardiac biomarkers of
      necrosis, who were admitted to the Cardiac Decision Unit of our institution. All
      patients underwent AS-CMR. A negative AS-CMR was defined as absence of all the
      following: regional wall motion abnormalities at rest; perfusion defects during
      stress (adenosine) and rest; and myocardial scar on late gadolinium enhancement
      images. The patients were followed for a mean of 277 (range 161-462) days. The
      primary end point was defined as the combination of cardiac death, nonfatal acute
      myocardial infarction, re-hospitalization for chest pain, obstructive coronary
      artery disease (>50% coronary stenosis on invasive angiography) and coronary
      revascularization. RESULTS: In 14 patients (13.6%), AS-CMR was positive. The
      remaining 89 patients (86.4%), who had negative AS-CMR, were discharged. No
      patient with negative AS-CMR reached the primary end-point during follow-up. The
      negative predictive value of AS-CMR was 100%. CONCLUSION: AS-CMR holds promise as
      a useful tool to rule out significant coronary artery disease in patients with
      low-risk chest pain. Patients with negative AS-CMR have an excellent short and
      mid-term prognosis.

PMID- 19772588
TI  - CRK9 contributes to regulation of mitosis and cytokinesis in the procyclic form
      of Trypanosoma brucei.
AB  - BACKGROUND: The Trypanosoma brucei cell cycle is regulated by combinations of
      cyclin/CRKs (cdc2 related kinases). Recently, two additional cyclins (CYC10,
      CYC11) and six new CRK (CRK7-12) homologues were identified in the T. brucei
      genome database 12. RESULTS: Individual RNAi knockdowns of these new proteins in
      the procyclic form of T. brucei showed no apparent phenotype except for the CRK9
      depletion, which enriched the cells in G2/M phase. But a similar CRK9 knockdown
      in the bloodstream form caused no apparent phenotype. CRK9 lacks the typical
      PSTAIRE motif for cyclin binding and the phenylalanine "gatekeeper" but binds to
      cyclin B2 in vitro and localizes to the nucleus in both forms of T. brucei. CRK9
      depleted procyclic-form generated no detectable anucleate cells, suggesting an
      inhibition of cytokinesis by CRK9 depletion as well. The knockdown enriched cells
      with one nucleus, one kinetoplast and two closely associated basal bodies with an
      average distance of 1.08 mm in between, which was shorter than the control value
      of 1.36 microm, and the cells became morphologically deformed and rounded with
      time. CONCLUSION: CRK9 may play a role in mediating the segregation between the
      two kinetoplast/basal body pairs prior to cytokinetic initiation. Since such a
      segregation over a relatively significant distance is essential for cytokinetic
      initiation only in the procyclic but may not be in the bloodstream form, CRK9
      could be specifically involved in regulating cytokinetic initiation in the
      procyclic form of T. brucei.

PMID- 19772589
TI  - RCMAT: a regularized covariance matrix approach to testing gene sets.
AB  - BACKGROUND: Gene sets are widely used to interpret genome-scale data. Analysis
      techniques that make better use of the correlation structure of microarray data
      while addressing practical "n<p" concerns could provide a real increase in power.
      However correlation structure is hard to estimate with typical genomics sample
      sizes. In this paper we present an extension of a classical multivariate
      procedure that confronts this challenge by the use of a regularized covariance
      matrix. RESULTS: We evaluated our testing procedure using both simulated data and
      a widely analyzed diabetes data set. We compared our approach to another popular
      multivariate test for both sets of data. Our results suggest an increase in power
      for detecting gene set differences can be obtained using our approach relative to
      the popular multivariate test with no increase in the false positive rate.
      CONCLUSION: Our regularized covariance matrix multivariate approach to gene set
      testing showed promise in both real and simulated data comparisons. Our findings
      are consistent with the recent literature in gene set methodology.

PMID- 19772590
TI  - A heteroskedastic error covariance matrix estimator using a first-order
      conditional autoregressive Markov simulation for deriving asympotical efficient
      estimates from ecological sampled Anopheles arabiensis aquatic habitat
      covariates.
AB  - BACKGROUND: Autoregressive regression coefficients for Anopheles arabiensis
      aquatic habitat models are usually assessed using global error techniques and are
      reported as error covariance matrices. A global statistic, however, will
      summarize error estimates from multiple habitat locations. This makes it
      difficult to identify where there are clusters of An. arabiensis aquatic habitats
      of acceptable prediction. It is therefore useful to conduct some form of spatial
      error analysis to detect clusters of An. arabiensis aquatic habitats based on
      uncertainty residuals from individual sampled habitats. In this research, a
      method of error estimation for spatial simulation models was demonstrated using
      autocorrelation indices and eigenfunction spatial filters to distinguish among
      the effects of parameter uncertainty on a stochastic simulation of ecological
      sampled Anopheles aquatic habitat covariates. A test for diagnostic checking
      error residuals in an An. arabiensis aquatic habitat model may enable
      intervention efforts targeting productive habitats clusters, based on
      larval/pupal productivity, by using the asymptotic distribution of parameter
      estimates from a residual autocovariance matrix. The models considered in this
      research extends a normal regression analysis previously considered in the
      literature. METHODS: Field and remote-sampled data were collected during July
      2006 to December 2007 in Karima rice-village complex in Mwea, Kenya. SAS 9.1.4
      was used to explore univariate statistics, correlations, distributions, and to
      generate global autocorrelation statistics from the ecological sampled datasets.
      A local autocorrelation index was also generated using spatial covariance
      parameters (i.e., Moran's Indices) in a SAS/GIS database. The Moran's statistic
      was decomposed into orthogonal and uncorrelated synthetic map pattern components
      using a Poisson model with a gamma-distributed mean (i.e. negative binomial
      regression). The eigenfunction values from the spatial configuration matrices
      were then used to define expectations for prior distributions using a Markov
      chain Monte Carlo (MCMC) algorithm. A set of posterior means were defined in
      WinBUGS 1.4.3. After the model had converged, samples from the conditional
      distributions were used to summarize the posterior distribution of the
      parameters. Thereafter, a spatial residual trend analyses was used to evaluate
      variance uncertainty propagation in the model using an autocovariance error
      matrix. RESULTS: By specifying coefficient estimates in a Bayesian framework, the
      covariate number of tillers was found to be a significant predictor, positively
      associated with An. arabiensis aquatic habitats. The spatial filter models
      accounted for approximately 19% redundant locational information in the
      ecological sampled An. arabiensis aquatic habitat data. In the residual error
      estimation model there was significant positive autocorrelation (i.e., clustering
      of habitats in geographic space) based on log-transformed larval/pupal data and
      the sampled covariate depth of habitat. CONCLUSION: An autocorrelation error
      covariance matrix and a spatial filter analyses can prioritize mosquito control
      strategies by providing a computationally attractive and feasible description of
      variance uncertainty estimates for correctly identifying clusters of prolific An.
      arabiensis aquatic habitats based on larval/pupal productivity.

PMID- 19772591
TI  - Gravity, a regulation factor in the differentiation of rat bone marrow
      mesenchymal stem cells.
AB  - BACKGROUND: Stem cell therapy has emerged as a potential therapeutic option for
      tissue engineering and regenerative medicine, but many issues remain to be
      resolved, such as the amount of seed cells, committed differentiation and the
      efficiency. Several previous studies have focused on the study of chemical
      inducement microenvironments. In the present study, we investigated the effects
      of gravity on the differentiation of bone marrow mesenchymal stem cells (BMSCs)
      into force-sensitive or force-insensitive cells. METHODS AND RESULTS: Rat BMSCs
      (rBMSCs) were cultured under hypergravity or simulated microgravity (SMG)
      conditions with or without inducement medium. The expression levels of the
      characteristic proteins were measured and analyzed using immunocytochemical, RT
      PCR and Western-blot analyses. After treatment with 5-azacytidine and
      hypergravity, rBMSCs expressed more characteristic proteins of cardiomyocytes
      such as cTnT, GATA4 and beta-MHC; however, fewer such proteins were seen with
      SMG. After treating rBMSCs with osteogenic inducer and hypergravity, there were
      marked increases in the expression levels of ColIA1, Cbfa1 and ALP. Reverse
      results were obtained with SMG. rBMSCs treated with adipogenic inducer and SMG
      expressed greater levels of PPARgamma. Greater levels of Cbfa1- or cTnT-positive
      cells were observed under hypergravity without inducer, as shown by FACS
      analysis. These results indicate that hypergravity induces differentiation of
      rBMSCs into force-sensitive cells (cardiomyocytes and osteoblasts), whereas SMG
      induces force-insensitive cells (adipocytes). CONCLUSION: Taken together, we
      conclude that gravity is an important factor affecting the differentiation of
      rBMSCs; this provides a new avenue for mechanistic studies of stem cell
      differentiation and a new approach to obtain more committed differentiated or
      undifferentiated cells.

PMID- 19772592
TI  - Antimicrobial resistance profiling and molecular subtyping of Campylobacter spp.
      from processed turkey.
AB  - BACKGROUND: Campylobacter is a major cause of human disease worldwide and poultry
      are identified as a significant source of this pathogen. Most disease in humans
      is associated with the consumption of contaminated poultry or cross-contamination
      with other foods. The primary drugs of choice for treatment of human
      campylobacteriosis include erythromycin and ciprofloxacin. In this study, we
      investigated the prevalence of resistance to erythromycin and ciprofloxacin in
      Campylobacter isolates recovered from turkey carcasses at two processing plants
      in the Upper Midwest US. Further analysis of a subset of isolates was carried out
      to assess resistance and genotype profiles. RESULTS: Campylobacter isolates from
      plant A (n = 439; including 196 C. coli and 217 C. jejuni) and plant B (n = 362,
      including 281 C. coli and 62 C. jejuni) were tested for susceptibility to
      ciprofloxacin and erythromycin using agar dilution. C. coli were more frequently
      resistant than C. jejuni in both plants, including resistance to ciprofloxacin
      (28% of C. jejuni and 63% of C. coli, plant B; and 11% of C. coli, plant A).
      Erythromycin resistance was low among C. jejuni (0% plant A and 0.3% plant B)
      compared to C. coli (41%, plant A and 17%, plant B). One hundred resistant and
      susceptible isolates were selected for additional antimicrobial susceptibility
      testing, restriction fragment length polymorphism analysis of the flaA gene (fla
      typing), and pulsed-field gel electrophoresis (PFGE). Fla-PFGE types obtained (n
      = 37) were associated with a specific plant with the exception of one type that
      was isolated from both plants. C. coli isolates (n = 65) were grouped into 20
      types, while C. jejuni isolates (n = 35) were grouped into 17 types. Most
      isolates with identical fla-PFGE patterns shared identical or very similar
      antimicrobial resistance profiles. PFGE alone and composite analysis using fla
      PFGE with resistance profiles separated C. jejuni and C. coli into distinct
      groups. CONCLUSION: Ciprofloxacin and erythromycin resistance in Campylobacter
      recovered from processed turkey occurred more frequently among C. coli than C.
      jejuni. Fla-PFGE types were associated with a particular species, antimicrobial
      resistance profiles, and a specific plant. Molecular subtyping in this study
      provided more information about the relationships among antimicrobial-resistant
      Campylobacter at the processing level.

PMID- 19772593
TI  - Quantitative gait analysis under dual-task in older people with mild cognitive
      impairment: a reliability study.
AB  - BACKGROUND: Reliability of quantitative gait assessment while dual-tasking
      (walking while doing a secondary task such as talking) in people with cognitive
      impairment is unknown. Dual-tasking gait assessment is becoming highly important
      for mobility research with older adults since better reflects their performance
      in the basic activities of daily living. Our purpose was to establish the test
      retest reliability of assessing quantitative gait variables using an electronic
      walkway in older adults with mild cognitive impairment (MCI) under single and
      dual-task conditions. METHODS: The gait performance of 11 elderly individuals
      with MCI was evaluated using an electronic walkway (GAITRite System) in two
      sessions, one week apart. Six gait parameters (gait velocity, step length, stride
      length, step time, stride time, and double support time) were assessed under two
      conditions: single-task (sG: usual walking) and dual-task (dG: counting backwards
      from 100 while walking). Test-retest reliability was determined using intra-class
      correlation coefficient (ICC). Gait variability was measured using coefficient of
      variation (CoV). RESULTS: Eleven participants (average age = 76.6 years, SD =
      7.3) were assessed. They were high functioning (Clinical Dementia Rating Score =
      0.5) with a mean Mini-Mental Status Exam (MMSE) score of 28 (SD = 1.56), and a
      mean Montreal Cognitive Assessment (MoCA) score of 22.8 (SD = 1.23). Under dual
      task conditions, mean gait velocity (GV) decreased significantly (sGV = 119.11 +/
      20.20 cm/s; dGV = 110.88 +/- 19.76 cm/s; p = 0.005). Additionally, under dual
      task conditions, higher gait variability was found on stride time, step time, and
      double support time. Test-retest reliability was high (ICC>0.85) for the six
      parameters evaluated under both conditions. CONCLUSION: In older people with MCI,
      variability of time-related gait parameters increased with dual-tasking
      suggesting cognitive control of gait performance. Assessment of quantitative gait
      variables using an electronic walkway is highly reliable under single and dual
      task conditions. The presence of cognitive impairment did not preclude
      performance of dual-tasking in our sample supporting that this methodology can be
      reliably used in cognitive impaired older individuals.

PMID- 19772594
TI  - Association analyses of the INSIG2 polymorphism in the obesity and cholesterol
      levels of Korean populations.
AB  - BACKGROUND: While INSIG2 has been reported to be associated with BMI in many
      populations, conflicting results have prevented consensus over its role. In
      analyses of mice and cell cultures the gene has been found to be involved in the
      regulation of cholesterol synthesis; however, no relationship has been found with
      cholesterol metabolism in human epidemiological research. Therefore, this study
      attempts to assess the effect of rs7566605 near INSIG2 on both obesity- and
      cholesterol-related traits in Koreans. METHODS: The rs7566605 polymorphism was
      genotyped with 2,364 Koreans, and associations with obesity- and cholesterol
      related traits were analyzed statistically via an ANOVA or T-test. RESULTS:
      Replication of an association with BMI, WHR, fat mass, fat percent, and abdominal
      fat area failed, and the C allele of rs7566605 was not associated significantly
      with total cholesterol, HDL cholesterol, or triglyceride. However, it was found
      in a meta-analysis of a dominant model that the C allele of rs7566605 appeared to
      affect the level of the total cholesterol, especially in female subjects.
      CONCLUSION: We failed to show associations of rs7566605 with cholesterol- and
      obesity-related phenotypes, although we newly suggest the possible involvement of
      INSIG2 with the plasma level of the total cholesterol in women.

PMID- 19772595
TI  - Non-linear dielectric spectroscopy of microbiological suspensions.
AB  - BACKGROUND: Non-linear dielectric spectroscopy (NLDS) of microorganism was
      characterized by the generation of harmonics in the polarization current when a
      microorganism suspension was exposed to a sinusoidal electric field. The
      biological nonlinear response initially described was not well verified by other
      authors and the results were susceptible to ambiguous interpretation. In this
      paper NLDS was performed to yeast suspension in tripolar and tetrapolar
      configuration with a recently developed analyzer. METHODS: Tripolar analysis was
      carried out by applying sinusoidal voltages up to 1 V at the electrode interface.
      Tetrapolar analysis was carried on with sinusoidal field strengths from 0.1 V cm(
      1) to 70 V cm(-1). Both analyses were performed within a frequency range from 1
      Hz through 100 Hz. The harmonic amplitudes were Fourier-analyzed and expressed in
      dB. The third harmonic, as reported previously, was investigated. Statistical
      analysis (ANOVA) was used to test the effect of inhibitor an activator of the
      plasma membrane enzyme in the measured response. RESULTS: No significant non
      linearities were observed in tetrapolar analysis, and no observable changes
      occurred when inhibitor and activator were added to the suspension. Statistical
      analysis confirmed these results.When a pure sinus voltage was applied to an
      electrode-yeast suspension interface, variations higher than 25 dB for the 3rd
      harmonic were observed. Variation higher than 20 dB in the 3rd harmonics has also
      been found when adding an inhibitor or activator of the membrane-bounded enzymes.
      These variations did not occur when the suspension was boiled. DISCUSSION: The
      lack of result in tetrapolar cells suggest that there is no, if any, harmonic
      generation in microbiological bulk suspension. The non-linear response observed
      was originated in the electrode-electrolyte interface. The frequency and voltage
      windows observed in previous tetrapolar analysis were repeated in the tripolar
      measurements, but maximum were not observed at the same values. CONCLUSION:
      Contrary to previous assertions, no repeatable dielectric non-linearity was
      exhibited in the bulk suspensions tested under the field and frequency condition
      reported with this recently designed analyzer. Indeed, interface related
      harmonics were observed and monitored during biochemical stimuli. The changes
      were coherent with the expected biological response.

PMID- 19772596
TI  - The HAART cell phone adherence trial (WelTel Kenya1): a randomized controlled
      trial protocol.
AB  - BACKGROUND: The objectives are to compare the effectiveness of cell phone
      supported SMS messaging to standard care on adherence, quality of life,
      retention, and mortality in a population receiving antiretroviral therapy (ART)
      in Nairobi, Kenya. METHODS AND DESIGN: A multi-site randomized controlled open
      label trial. A central randomization centre provided opaque envelopes to allocate
      treatments. Patients initiating ART at three comprehensive care clinics in Kenya
      will be randomized to receive either a structured weekly SMS ('short message
      system' or text message) slogan (the intervention) or current standard of care
      support mechanisms alone (the control). Our hypothesis is that using a structured
      mobile phone protocol to keep in touch with patients will improve adherence to
      ART and other patient outcomes. Participants are evaluated at baseline, and then
      at six and twelve months after initiating ART. The care providers keep a weekly
      study log of all phone based communications with study participants. Primary
      outcomes are self-reported adherence to ART and suppression of HIV viral load at
      twelve months scheduled follow-up. Secondary outcomes are improvements in health,
      quality of life, social and economic factors, and retention on ART. Primary
      analysis is by 'intention-to-treat'. Sensitivity analysis will be used to assess
      per-protocol effects. Analysis of covariates will be undertaken to determine
      factors that contribute or deter from expected and determined outcomes.
      DISCUSSION: This study protocol tests whether a novel structured mobile phone
      intervention can positively contribute to ART management in a resource-limited
      setting.

PMID- 19772597
TI  - Development of a high-throughput method for the systematic identification of
      human proteins nuclear translocation potential.
AB  - BACKGROUND: Important clues to the function of novel and uncharacterized proteins
      can be obtained by identifying their ability to translocate in the nucleus. In
      addition, a comprehensive definition of the nuclear proteome undoubtedly
      represents a key step toward a better understanding of the biology of this
      organelle. Although several high-throughput experimental methods have been
      developed to explore the sub-cellular localization of proteins, these methods
      tend to focus on the predominant localizations of gene products and may fail to
      provide a complete catalog of proteins that are able to transiently locate into
      the nucleus. RESULTS: We have developed a method for examining the nuclear
      localization potential of human gene products at the proteome scale by adapting a
      mammalian two-hybrid system we have previously developed. Our system is composed
      of three constructs co-transfected into a mammalian cell line. First, it contains
      a PCR construct encoding a fusion protein composed of a tested protein, the PDZ
      protein TIP-1, and the transactivation domain of TNNC2 (referred to as ACT
      construct). Second, our system contains a PCR construct encoding a fusion protein
      composed of the DNA binding domain of GAL4 and the PDZ binding domain of rhotekin
      (referred to as the BIND construct). Third, a GAL4-responsive luciferase reporter
      is used to detect the reconstitution of a transcriptionally active BIND-ACT
      complex through the interaction of TIP-1 and rhotekin, which indicates the
      ability of the tested protein to translocate into the nucleus. We validated our
      method in a small-scale feasibility study by comparing it to green fluorescent
      protein (GFP) fusion-based sub-cellular localization assays, sequence-based
      computational prediction of protein sub-cellular localization, and current sub
      cellular localization data available from the literature for 22 gene products.
      CONCLUSION: Our reporter-based system can rapidly screen gene products for their
      ability to be translocated to the nucleus. Large-scale applications of the system
      presented herein should provide invaluable information for a more complete
      biological atlas.

PMID- 19772598
TI  - A global framework for action to improve the primary care response to chronic non
      communicable diseases: a solution to a neglected problem.
AB  - BACKGROUND: Although in developing countries the burden of morbidity and
      mortality due to infectious diseases has often overshadowed that due to chronic
      non-communicable diseases (NCDs), there is evidence now of a shift of attention
      to NCDs. DISCUSSION: Decreasing the chronic NCD burden requires a two-pronged
      approach: implementation of the multisectoral policies aimed at decreasing
      population-level risks for NCDs, and effective and affordable delivery of primary
      care interventions for patients with chronic NCDs. The primary care response to
      common NCDs is often unstructured and inadequate. We therefore propose a
      programmatic, standardized approach to the delivery of primary care interventions
      for patients with NCDs, with a focus on hypertension, diabetes mellitus, chronic
      airflow obstruction, and obesity. The benefits of this approach will extend to
      patients with related conditions, e.g. those with chronic kidney disease caused
      by hypertension or diabetes. This framework for a "public health approach" is
      informed by experience of scaling up interventions for chronic infectious
      diseases (tuberculosis and HIV). The lessons learned from progress in rolling out
      these interventions include the importance of gaining political commitment,
      developing a robust strategy, delivering standardised interventions, and ensuring
      rigorous monitoring and evaluation of progress towards defined targets. The goal
      of the framework is to reduce the burden of morbidity, disability and premature
      mortality related to NCDs through a primary care strategy which has three
      elements: 1) identify and address modifiable risk factors, 2) screen for common
      NCDs and 3) and diagnose, treat and follow-up patients with common NCDs using
      standard protocols. The proposed framework for NCDs borrows the same elements as
      those developed for tuberculosis control, comprising a goal, strategy and targets
      for NCD control, a package of interventions for quality care, key operations for
      national implementation of these interventions (political commitment, case
      finding among people attending primary care services, standardised diagnostic and
      treatment protocols, regular drug supply, and systematic monitoring and
      evaluation), and indicators to measure progress towards increasing the impact of
      primary care interventions on chronic NCDs. The framework needs evaluation, then
      adaptation in different settings. SUMMARY: A framework for a programmatic "public
      health approach" has the potential to improve on the current unstructured
      approach to primary care of people with chronic NCDs. Research to establish the
      cost, value and feasibility of implementing the framework will pave the way for
      international support to extend the benefit of this approach to the millions of
      people worldwide with chronic NCDs.

PMID- 19772599
TI  - Paediatric HIV management at primary care level: an evaluation of the integrated
      management of childhood illness (IMCI) guidelines for HIV.
AB  - BACKGROUND: Integrated Management of Childhood Illness (IMCI) is a WHO/UNICEF
      strategy to improve child survival in resource poor settings. South Africa
      adopted IMCI in 1997, and IMCI guidelines were adapted to include identification
      and management of HIV infected and exposed children. This study describes the
      validity of the IMCI/HIV algorithm when used by IMCI experts, the use of IMCI/HIV
      guidelines by IMCI trained health workers in routine clinical practice, and the
      burden of HIV among children under 5 years attending first level health
      facilities. METHODS: Seventy seven randomly selected IMCI trained health workers
      were observed in 74 health facilities in two provinces of South Africa.
      Consultations were observed with 1357 sick children; each child was reassessed by
      an IMCI expert to confirm the correct findings. Consent was requested for HIV
      testing of all children who attended with a parent or legal guardian. Positive
      rapid HIV tests were confirmed with HIV PCR in children aged less than 18 months.
      HIV positive children had a CD4 count and HIV clinical staging done. RESULTS: Of
      1064 children with HIV results available, 76 (7.1% CI: 5.7% - 8.9%) children were
      confirmed HIV positive. IMCI experts using the HIV algorithm classified 54/76
      (71.1% CI: 59.5%-80.9%) HIV positive children as suspected symptomatic HIV, and
      15/22 remaining HIV positive children were identified as HIV exposed. Therefore,
      69/76 (90.8% CI: 81.9-96.2) HIV infected children were identified by IMCI
      experts. No classification was made for HIV by observed health workers in
      899/1357(66.2%) children.906/1243(72.9%) mothers had been tested previously for
      HIV, of whom 221(24.4%) reported testing positive. Of 221 children therefore
      identified as HIV exposed, only 78(35.3%) had been tested for HIV within routine
      services. CONCLUSION: The HIV algorithm is a valid tool for identifying HIV
      infected and exposed children when correctly and comprehensively implemented.
      However, it is not being used by IMCI trained health workers in routine practise,
      leading to a failure to implement life saving interventions.

PMID- 19772600
TI  - A comparison of classification methods for predicting Chronic Fatigue Syndrome
      based on genetic data.
AB  - BACKGROUND: In the studies of genomics, it is essential to select a small number
      of genes that are more significant than the others for the association studies of
      disease susceptibility. In this work, our goal was to compare computational tools
      with and without feature selection for predicting chronic fatigue syndrome (CFS)
      using genetic factors such as single nucleotide polymorphisms (SNPs). METHODS: We
      employed the dataset that was original to the previous study by the CDC Chronic
      Fatigue Syndrome Research Group. To uncover relationships between CFS and SNPs,
      we applied three classification algorithms including naive Bayes, the support
      vector machine algorithm, and the C4.5 decision tree algorithm. Furthermore, we
      utilized feature selection methods to identify a subset of influential SNPs. One
      was the hybrid feature selection approach combining the chi-squared and
      information-gain methods. The other was the wrapper-based feature selection
      method. RESULTS: The naive Bayes model with the wrapper-based approach performed
      maximally among predictive models to infer the disease susceptibility dealing
      with the complex relationship between CFS and SNPs. CONCLUSION: We demonstrated
      that our approach is a promising method to assess the associations between CFS
      and SNPs.

PMID- 19772601
TI  - Pathogenesis of vestibular schwannoma in ring chromosome 22.
AB  - BACKGROUND: Ring chromosome 22 is a rare human constitutional cytogenetic
      abnormality. Clinical features of neurofibromatosis type 1 and 2 as well as
      different tumour types have been reported in patients with ring chromosome 22.
      The pathogenesis of these tumours is not always clear yet. METHODS: We report on
      a female patient with a ring chromosome 22 presenting with severe mental
      retardation, autistic behaviour, cafe-au-lait macules and facial dysmorphism.
      Peripheral blood lymphocytes were karyotyped and array CGH was performed on
      extracted DNA. At the age of 20 years she was diagnosed with a unilateral
      vestibular schwannoma. Tumour cells were analyzed by karyotyping, array CGH and
      NF2 mutation analysis. RESULTS: Karyotype on peripheral blood lymphocytes
      revealed a ring chromosome 22 in all analyzed cells. A 1 Mb array CGH experiment
      on peripheral blood DNA showed a deletion of 5 terminal clones on the long arm of
      chromosome 22. Genetic analysis of vestibular schwannoma tissue revealed loss of
      the ring chromosome 22 and a somatic second hit in the NF2 gene on the remaining
      chromosome 22. CONCLUSION: We conclude that tumours can arise by the combination
      of loss of the ring chromosome and a pathogenic NF2 mutation on the remaining
      chromosome 22 in patients with ring chromosome 22. Our findings indicate that
      patients with a ring 22 should be monitored for NF2-related tumours starting in
      adolescence.

PMID- 19772602
TI  - Unintended spread of a biosafety level 2 recombinant retrovirus.
AB  - BACKGROUND: Contamination of vertebrate cell lines with animal retroviruses has
      been documented repeatedly before. Although such viral contaminants can be easily
      identified with high sensitivity by PCR, it is impossible to screen for all
      potential contaminants. Therefore, we explored two novel methods to identify
      viral contaminations in cell lines without prior knowledge of the kind of
      contaminant. RESULTS: The first hint for the presence of contaminating
      retroviruses in one of our cell lines was obtained by electron microscopy of
      exosome-like vesicles released from the supernatants of transfected 293T cells.
      Random amplification of particle associated RNAs (PAN-PCR) from supernatant of
      contaminated 293T cells and sequencing of the amplicons revealed several
      nucleotide sequences showing highest similarity to either murine leukemia virus
      (MuLV) or squirrel monkey retrovirus (SMRV). Subsequent mass spectrometry
      analysis confirmed our findings, since we could identify several peptide
      sequences originating from monkey and murine retroviral proteins. Quantitative
      PCRs were established for both viruses to test currently cultured cell lines as
      well as liquid nitrogen frozen cell stocks. Gene fragments for both viruses could
      be detected in a broad range of permissive cell lines from multiple species.
      Furthermore, experimental infections of cells negative for these viruses showed
      that both viruses replicate rapidly to high loads. We decided to further analyze
      the genomic sequence of the MuLV-like contaminant virus. Surprisingly it was
      neither identical to MuLV nor to the novel xenotropic MuLV related retrovirus
      (XMRV) but showed 99% identity to a synthetic retrovirus which was engineered in
      the 1980s. CONCLUSION: The high degree of nucleotide identity suggests unintended
      spread of a biosafety level 2 recombinant virus, which could also affect the risk
      assessment of gene-modified organisms released from contaminated cell cultures.
      The study further indicates that both mass spectrometry and PAN-PCR are powerful
      methods to identify viral contaminations in cell lines without prior knowledge of
      the kind of contaminant. Both methods might be useful tools for testing cell
      lines before using them for critical purposes.

PMID- 19772603
TI  - Strategies for improving patient recruitment to focus groups in primary care: a
      case study reflective paper using an analytical framework.
AB  - BACKGROUND: Recruiting to primary care studies is complex. With the current drive
      to increase numbers of patients involved in primary care studies, we need to know
      more about successful recruitment approaches. There is limited evidence on
      recruitment to focus group studies, particularly when no natural grouping exists
      and where participants do not regularly meet. The aim of this paper is to reflect
      on recruitment to a focus group study comparing the methods used with existing
      evidence using a resource for research recruitment, PROSPeR (Planning Recruitment
      Options: Strategies for Primary Care). METHODS: The focus group formed part of
      modelling a complex intervention in primary care in the Resources for Effective
      Sleep Treatment (REST) study. Despite a considered approach at the design stage,
      there were a number of difficulties with recruitment. The recruitment strategy
      and subsequent revisions are detailed. RESULTS: The researchers' modifications to
      recruitment, justifications and evidence from the literature in support of them
      are presented. Contrary evidence is used to analyse why some aspects were
      unsuccessful and evidence is used to suggest improvements. Recruitment to focus
      group studies should be considered in two distinct phases; getting potential
      participants to contact the researcher, and converting those contacts into
      attendance. The difficulty of recruitment in primary care is underemphasised in
      the literature especially where people do not regularly come together, typified
      by this case study of patients with sleep problems. CONCLUSION: We recommend
      training GPs and nurses to recruit patients during consultations. Multiple
      recruitment methods should be employed from the outset and the need to build
      topic related non-financial incentives into the group meeting should be
      considered. Recruitment should be monitored regularly with barriers addressed
      iteratively as a study progresses.

PMID- 19772604
TI  - Duration of red blood cell storage is associated with increased incidence of deep
      vein thrombosis and in hospital mortality in patients with traumatic injuries.
AB  - INTRODUCTION: In critically ill patients the relationship between the storage age
      of red blood cells (RBCs) transfused and outcomes are controversial. To determine
      if duration of RBC storage is associated with adverse outcomes we studied
      critically ill trauma patients requiring transfusion. METHODS: This retrospective
      cohort study included patients with traumatic injuries transfused >or=5 RBC
      units. Patients transfused >or= 1 unit of RBCs with a maximum storage age of up
      to 27 days were compared with those transfused 1 or more RBC units with a maximum
      storage age of >or= 28 days. These study groups were also matched by RBC amount
      (+/- 1 unit) transfused. Primary outcomes were deep vein thrombosis and in
      hospital mortality. RESULTS: Two hundred and two patients were studied with 101
      in both decreased and increased RBC age groups. No differences in admission vital
      signs, laboratory values, use of DVT prophylaxis, blood products or Injury
      Severity Scores were measured between study groups. In the decreased compared
      with increased RBC storage age groups, deep vein thrombosis occurred in 16.7% vs
      34.5%, (P = 0.006), and mortality was 13.9% vs 26.7%, (P = 0.02), respectively.
      Patients transfused RBCs of increased storage age had an independent association
      with mortality, OR (95% CI), 4.0 (1.34 - 11.61), (P = 0.01), and had an increased
      incidence of death from multi-organ failure compared with the decreased RBC age
      group, 16% vs 7%, respectively, (P = 0.037). CONCLUSIONS: In trauma patients
      transfused >/=5 units of RBCs, transfusion of RBCs >or= 28 days of storage may be
      associated with deep vein thrombosis and death from multi-organ failure.

PMID- 19772606
TI  - Harmonization of monographic standards is needed to ensure the quality of Chinese
      medicinal materials.
AB  - This article provides an overview on the regulations of Chinese medicinal
      materials (CMMs) in various countries and regions. Harmonization of CMM
      monographs would provide standards for the quality control of CMM products and
      play an important role in the modernization and globalization of Chinese
      medicine. A harmonized regulatory system would improve the quality of CMMs
      thereby ensuring the safety of the products and assisting Chinese medicine
      practitioners in their practice. The fast growing demand worldwide for
      traditional medicines calls for harmonized monographic standards to safeguard the
      safety and quality of CMM products.

PMID- 19772605
TI  - Transplantation of human neural stem cells transduced with Olig2 transcription
      factor improves locomotor recovery and enhances myelination in the white matter
      of rat spinal cord following contusive injury.
AB  - BACKGROUND: Contusive spinal cord injury is complicated by a delayed loss of
      oligodendrocytes, resulting in chronic progressive demyelination. Therefore,
      transplantation strategies to provide oligodendrocyte lineage cells and to
      enhance the extent of myelination appear to be justified for spinal cord repair.
      The present study investigated whether transplantation of human neural stem cells
      (NSCs) genetically modified to express Olig2 transcription factor, an essential
      regulator of oligodendrocyte development, can improve locomotor recovery and
      enhance myelination in a rat contusive spinal cord injury model. RESULTS: HB1.F3
      (F3) immortalized human NSC line was transduced with a retroviral vector encoding
      Olig2, an essential regulator of oligodendrocyte development. Overexpression of
      Olig2 in human NSCs (F3.Olig2) induced activation of NKX2.2 and directed
      differentiation of NSCs into oligodendrocyte lineage cells in vitro. Introduction
      of Olig2 conferred higher proliferative activity, and a much larger number of
      F3.Olig2 NSCs were detected by 7 weeks after transplantation into contused spinal
      cord than that of parental F3 NSCs. F3.Olig2 NSCs exhibited frequent migration
      towards the white matter, whereas F3 NSCs were mostly confined to the gray matter
      or around the lesion cavities. Most of F3.Olig2 NSCs occupying the spared white
      matter differentiated into mature oligodendrocytes. Transplantation of F3.Olig2
      NSCs increased the volume of spared white matter and reduced the cavity volume.
      Moreover, F3.Olig2 grafts significantly increased the thickness of myelin sheath
      around the axons in the spared white matter. Finally, animals with F3.Olig2
      grafts showed an improvement in the quality of hindlimbs locomotion. CONCLUSION:
      Transplantation of NSCs genetically modified to differentiate into an
      oligodendrocytic lineage may be an effective strategy to improve functional
      outcomes following spinal cord trauma. The present study suggests that molecular
      factors governing cell fate decisions can be manipulated to enhance reparative
      potential of the cell-based therapy.

PMID- 19772607
TI  - The use of income information of census enumeration area as a proxy for the
      household income in a household survey.
AB  - BACKGROUND: Some of the Census Enumeration Areas' (CEA) information may help
      planning the sample of population studies but it can also be used for some
      analyses that require information that is more difficult to obtain at the
      individual or household level, such as income. This paper verifies if the income
      information of CEA can be used as a proxy for household income in a household
      survey. METHODS: A population-based survey conducted from January to December
      2003 obtained data from a probabilistic sample of 1,734 households of Niteroi,
      Rio de Janeiro, Brazil. Uniform semi-association models were adjusted in order to
      obtain information about the agreement/disagreement structure of data. The
      distribution of nutritional status categories of the population of Niteroi
      according to income quintiles was performed using both CEA- and household-level
      income measures and then compared using Wald statistics for homogeneity. Body
      mass index was calculated using body mass and stature data measured in the
      households and then used to define nutritional status categories according to the
      World Health Organization. All estimates and statistics were calculated
      accounting for the structural information of the sample design and a significance
      level lower than 5% was adopted. RESULTS: The classification of households in the
      quintiles of household income was associated with the classification of these
      households in the quintiles of CEA income. The distribution of the nutritional
      status categories in all income quintiles did not differ significantly according
      to the source of income information (household or CEA) used in the definition of
      quintiles. CONCLUSION: The structure of agreement/disagreement between quintiles
      of the household's monthly per capita income and quintiles of the head-of
      household's mean nominal monthly income of the CEA, as well as the results
      produced by these measures when they were associated with the nutritional status
      of the population, showed that the CEA's income information can be used when
      income information at the individual or household levels is not available.

PMID- 19772608
TI  - The intuitive use of laryngeal airway tools by first year medical students.
AB  - BACKGROUND: Providing a secured airway is of paramount importance in
      cardiopulmonary resuscitation. Although intubating the trachea is yet seen as
      gold standard, this technique is still reserved to experienced healthcare
      professionals. Compared to bag-valve facemask ventilation, however, the insertion
      of a laryngeal mask airway offers the opportunity to ventilate the patient
      effectively and can also be placed easily by lay responders. Obviously, it might
      be inserted without detailed background knowledge.The purpose of the study was to
      investigate the intuitive use of airway devices by first-year medical students as
      well as the effect of a simple, but well-directed training programme. Retention
      of skills was re-evaluated six months thereafter. METHODS: The insertion of a LMA
      Classic and a LMA-Fastrach performed by inexperienced medical students was
      compared in an airway model. The improvement on their performance after a
      training programme of overall two hours was examined afterwards. RESULTS: Prior
      to any instruction, mean time to correct placement was 55.5 +/- 29.6 s for the
      LMA-Classic and 38.1 +/- 24.9 s for the LMA-Fastrach. Following training, time to
      correct placement decreased significantly with 22.9 +/- 13.5 s for the LMA
      Classic and 22.9 +/- 19.0 s for the LMA-Fastrach, respectively (p < 0.05). After
      six months, the results are comparable prior (55.6 +/- 29.9 vs 43.1 +/- 34.7 s)
      and after a further training period (23.5 +/- 13.2 vs 26.6 +/- 21.6, p < 0.05).
      CONCLUSION: Untrained laypersons are able to use different airway devices in a
      manikin and may therefore provide a secured airway even without having any
      detailed background knowledge about the tool. Minimal theoretical instruction and
      practical skill training can improve their performance significantly. However,
      refreshment of knowledge seems justified after six months.

PMID- 19772609
TI  - Saudi Arabian Y-Chromosome diversity and its relationship with nearby regions.
AB  - BACKGROUND: Human origins and migration models proposing the Horn of Africa as a
      prehistoric exit route to Asia have stimulated molecular genetic studies in the
      region using uniparental loci. However, from a Y-chromosome perspective, Saudi
      Arabia, the largest country of the region, has not yet been surveyed. To address
      this gap, a sample of 157 Saudi males was analyzed at high resolution using 67 Y
      chromosome binary markers. In addition, haplotypic diversity for its most
      prominent J1-M267 lineage was estimated using a set of 17 Y-specific STR loci.
      RESULTS: Saudi Arabia differentiates from other Arabian Peninsula countries by a
      higher presence of J2-M172 lineages. It is significantly different from Yemen
      mainly due to a comparative reduction of sub-Saharan Africa E1-M123 and Levantine
      J1-M267 male lineages. Around 14% of the Saudi Arabia Y-chromosome pool is
      typical of African biogeographic ancestry, 17% arrived to the area from the East
      across Iran, while the remainder 69% could be considered of direct or indirect
      Levantine ascription. Interestingly, basal E-M96* (n = 2) and J-M304* (n = 3)
      lineages have been detected, for the first time, in the Arabian Peninsula.
      Coalescence time for the most prominent J1-M267 haplogroup in Saudi Arabia (11.6
      +/- 1.9 ky) is similar to that obtained previously for Yemen (11.3 +/- 2) but
      significantly older that those estimated for Qatar (7.3 +/- 1.8) and UAE (6.8 +/-
      1.5). CONCLUSION: The Y-chromosome genetic structure of the Arabian Peninsula
      seems to be mainly modulated by geography. The data confirm that this area has
      mainly been a recipient of gene flow from its African and Asian surrounding
      areas, probably mainly since the last Glacial maximum onwards. Although rare deep
      rooting lineages for Y-chromosome haplogroups E and J have been detected, the
      presence of more basal clades supportive of the southern exit route of modern
      humans to Eurasian, were not found.

PMID- 19772610
TI  - Predictors of the early introduction of solid foods in infants: results of a
      cohort study.
AB  - BACKGROUND: The early introduction of solid foods before 4 months of age has been
      associated with an increased risk of diarrhoea in infancy and a greater risk of
      wheeze and increased percentage body fat and weight in childhood. The purpose of
      this study was to identify the level of compliance with national recommendations
      related to the timing of the introduction of solid foods and to describe the
      maternal and infant characteristics associated with the timing of the
      introduction of solids. METHODS: Subjects were 519 participants in the second
      longitudinal Perth Infant Feeding Study (PIFS II) recruited from two maternity
      hospitals in Perth, Western Australia in 2002/3. Data collected prior to, or
      shortly after discharge from hospital, and at 4, 10, 16, 22, 32, 40 and 52 weeks
      postpartum included timing of the introduction of solid foods and a variety of
      maternal and infant characteristics associated with the introduction of solid
      foods. Multivariate logistic regression was used to identify those factors
      associated with the risk of introducing solid foods early, which for the purposes
      of this study was defined as being before 17 weeks. RESULTS: The median age of
      introduction of solid foods was 17.6 weeks. In total, 44% of infants had received
      solids before 17 weeks and 93% of infants had received their first solids before
      26 weeks of age. The strongest independent predictors of the early introduction
      of solids were young maternal age, mother smoking prior to pregnancy and not
      fully breastfeeding at 4 weeks postpartum. In general, mothers introduced solids
      earlier than recommended because they perceived their baby to either need them or
      be ready for them. CONCLUSION: This study showed a high level of non-compliance
      among Australian mothers with the infant feeding recommendation related to the
      timing of solids that was current at the time. In order to improve compliance
      health professionals need to be aware of those groups least likely to comply with
      recommendations and their reasons for non-compliance. Infant feeding
      recommendations need to be evidence-based, uniformly supported by professionals
      and widely, clearly and consistently articulated if higher rates of compliance
      are to be achieved in the future.

PMID- 19772612
TI  - Incidence and risk factors for caesarean wound infection in Lagos Nigeria.
AB  - BACKGROUND: Post caesarean wound infection is not only a leading cause of
      prolonged hospital stay but a major cause of the widespread aversion to caesarean
      delivery in developing countries. In order to control and prevent post caesarean
      wound infection in our environment there is the need to access the relative
      contribution of each aetiologic factor. Though some studies in our environment
      have identified factors associated with post caesarean wound infection, none was
      specifically designed to address these issues prospectively or assess the
      relative contribution of each of the risk factors. FINDINGS: Prospective
      multicentre study over a period of 56 months in Lagos Nigeria. All consecutive
      and consenting women scheduled for caesarean section and meeting the inclusion
      criteria were enrolled into the study. Cases were all subjects with post
      caesarean wound infection. Those without wound infection served as controls. Data
      entry and analysis were performed using EPI-Info programme version 6 and SPSS for
      windows version 10.0.Eight hundred and seventeen women were enrolled into the
      study. Seventy six (9.3%) of these cases were complicated with wound infection.
      The proportion of subjects with body mass index greater than 25 was significantly
      higher among the subjects with wound infection (51.3%) than in the subjects
      without wound infection (33.9%) p = 0.011. There were also significantly higher
      proportions of subjects with prolonged rupture of membrane (p = 0.02), prolonged
      operation time (p = 0.001), anaemia (p = 0.031) and multiple vaginal examinations
      during labour (0.021) among the women that had wound infection compared to the
      women that did not have wound infection. After adjustment for confounders only
      prolonged rupture of membrane (OR = 4.45), prolonged operation time (OR = 2.87)
      and body max index > 25 (2.34) retained their association with post caesarean
      wound infection. CONCLUSION: Effort should be geared towards the prevention of
      prolonged rupture of fetal membrane and the reduction of prolonged operation time
      by the use of potent antibiotics, early intervention and use of good surgical
      technique. In obese women improved surgical technique and use of non absorbable
      sutures may suffice.

PMID- 19772611
TI  - Both ischemic preconditioning and ghrelin administration protect hippocampus from
      ischemia/reperfusion and upregulate uncoupling protein-2.
AB  - BACKGROUND: A major endogenous protective mechanism in many organs against
      ischemia/reperfusion (I/R) injury is ischemic preconditioning (IPC). By
      moderately uncoupling the mitochondrial respiratory chain and decreasing
      production of reactive oxygen species (ROS), IPC reduces apoptosis induced by I/R
      by reducing cytochrome c release from the mitochondria. One element believed to
      contribute to reduce ROS production is the uncoupling protein UCP2 (and UCP3 in
      the heart). Although its implication in IPC in the brain has been shown in vitro,
      no in vivo study of protein has shown its upregulation. Our first goal was to
      determine in rat hippocampus whether UCP2 protein upregulation was associated
      with IPC-induced protection and increased ROS production. The second goal was to
      determine whether the peptide ghrelin, which possesses anti-oxidant and
      protective properties, alters UCP2 mRNA levels in the same way as IPC during
      protection. RESULTS: After global forebrain ischemia (15 min) with 72 h
      reperfusion (I/R group), we found important neuronal lesion in the rat
      hippocampal CA1 region, which was reduced by a preceding 3-min preconditioning
      ischemia (IPC+I/R group), whereas the preconditioning stimulus alone (IPC group)
      had no effect. Compared to control, UCP2 protein labelling increased moderately
      in the I/R (+39%, NS) and IPC+I/R (+28%, NS) groups, and substantially in the IPC
      group (+339%, P < 0.05). Treatment with superoxide dismutase (10000 U/kg ip) at
      the time of a preconditioning ischemia greatly attenuated (-73%, P < 0.001) the
      increase in UCP2 staining at 72 h, implying a role of oxygen radicals in UCP2
      induction.Hippocampal UCP2 mRNA showed a moderate increase in I/R (+33%, P <
      0.05) and IPC+I/R (+40%, P < 0.05) groups versus control, and a large increase in
      the IPC group (+333%, P < 0.001). In ghrelin experiments, the I/R+ghrelin group
      (3 daily administrations) showed considerable protection of CA1 neurons versus
      I/R animals, and increased hippocampal UCP2 mRNA (+151%, P < 0.001). CONCLUSION:
      We confirm that IPC causes increased expression of UCP2 protein in vivo, at a
      moment appropriate for protection against I/R in the hippocampus. The two
      dissimilar protective strategies, IPC and ghrelin administration, were both
      associated with upregulated UCP2, suggesting that UCP2 may often represent a
      final common pathway in protection from I/R.

PMID- 19772613
TI  - Deep proteogenomics; high throughput gene validation by multidimensional liquid
      chromatography and mass spectrometry of proteins from the fungal wheat pathogen
      Stagonospora nodorum.
AB  - BACKGROUND: Stagonospora nodorum, a fungal ascomycete in the class
      dothideomycetes, is a damaging pathogen of wheat. It is a model for necrotrophic
      fungi that cause necrotic symptoms via the interaction of multiple effector
      proteins with cultivar-specific receptors. A draft genome sequence and annotation
      was published in 2007. A second-pass gene prediction using a training set of 795
      fully EST-supported genes predicted a total of 10762 version 2 nuclear-encoded
      genes, with an additional 5354 less reliable version 1 genes also retained.
      RESULTS: In this study, we subjected soluble mycelial proteins to proteolysis
      followed by 2D LC MALDI-MS/MS. Comparison of the detected peptides with the gene
      models validated 2134 genes. 62% of these genes (1324) were not supported by
      prior EST evidence. Of the 2134 validated genes, all but 188 were version 2
      annotations. Statistical analysis of the validated gene models revealed a
      preponderance of cytoplasmic and nuclear localised proteins, and proteins with
      intracellular-associated GO terms. These statistical associations are consistent
      with the source of the peptides used in the study. Comparison with a 6-frame
      translation of the S. nodorum genome assembly confirmed 905 existing gene
      annotations (including 119 not previously confirmed) and provided evidence
      supporting 144 genes with coding exon frameshift modifications, 604 genes with
      extensions of coding exons into annotated introns or untranslated regions (UTRs),
      3 new gene annotations which were supported by tblastn to NR, and 44 potential
      new genes residing within un-assembled regions of the genome. CONCLUSION: We
      conclude that 2D LC MALDI-MS/MS is a powerful, rapid and economical tool to aid
      in the annotation of fungal genomic assemblies.

PMID- 19772614
TI  - Attitude of young psychiatrists toward coercive measures in psychiatry: a case
      vignette study in Japan.
AB  - BACKGROUND: Every psychiatrist must pay careful attention to avoid violating
      human rights when initiating coercive treatments such as seclusion and restraint.
      However, these interventions are indispensable in clinical psychiatry, and they
      are often used as strategies to treat agitated patients. In this study, we
      investigated young psychiatrists' attitudes toward psychiatric coercive measures.
      METHODS: A total of 183 young psychiatrists participated as subjects in our
      study. A questionnaire with a case vignette describing a patient with acute
      psychosis was sent to the study subjects via the Internet or by mail. This
      questionnaire included scoring the necessity for hospitalization, and the
      likelihood of prescribing seclusion and/or restraint, on a 9-point Likert scale
      (with 9 indicating strong agreement). RESULTS: There was general agreement among
      the study subjects that the case should be admitted to a hospital (8.91 +/- 0.3)
      and secluded (8.43 +/- 1.0). The estimated length of hospitalization was 13.53 +/
      6.4 weeks. Regarding the likelihood of prescribing restraint, results showed
      great diversity (5.14 +/- 2.5 on 9-point scale); psychiatrists working at general
      hospitals scored significantly higher (6.25 +/- 2.5) than those working at
      university hospitals (5.02 +/- 2.3) or psychiatric hospitals (4.15 +/- 2.6). A
      two-group comparison of the length of inpatient care revealed a significant
      difference between those psychiatrists who scored 1-3 (n = 55, 14.22 +/- 7.4 wks)
      and those who scored 7-9 (n = 62, 12.22 +/- 4.0) regarding the need to use
      restraint. CONCLUSION: Our results may reflect the current dilemma in Japanese
      psychiatry wherein psychiatrists must initiate coercive measures to shorten
      hospitalization stays. This study prompted its subject psychiatrists to consider
      coercive psychiatric treatments.

PMID- 19772615
TI  - Prediction of antigenic epitopes on protein surfaces by consensus scoring.
AB  - BACKGROUND: Prediction of antigenic epitopes on protein surfaces is important for
      vaccine design. Most existing epitope prediction methods focus on protein
      sequences to predict continuous epitopes linear in sequence. Only a few structure
      based epitope prediction algorithms are available and they have not yet shown
      satisfying performance. RESULTS: We present a new antigen Epitope Prediction
      method, which uses ConsEnsus Scoring (EPCES) from six different scoring functions
      - residue epitope propensity, conservation score, side-chain energy score,
      contact number, surface planarity score, and secondary structure composition.
      Applied to unbounded antigen structures from an independent test set, EPCES was
      able to predict antigenic eptitopes with 47.8% sensitivity, 69.5% specificity and
      an AUC value of 0.632. The performance of the method is statistically similar to
      other published methods. The AUC value of EPCES is slightly higher compared to
      the best results of existing algorithms by about 0.034. CONCLUSION: Our work
      shows consensus scoring of multiple features has a better performance than any
      single term. The successful prediction is also due to the new score of residue
      epitope propensity based on atomic solvent accessibility.

PMID- 19772616
TI  - The rK39 strip test is non-predictor of clinical status for kala-azar.
AB  - BACKGROUND: The rK39 strip test is reported to be simple, sensitive, specific,
      non-invasive and economical test. Since this method is supposed to be patient
      friendly, it may easily be accepted for sero-epidemiological surveys. An attempt
      was made to evaluate the role of rK39 strip test in pre and post treatment phases
      of Kala azar, as a diagnostic and prognostic marker, in addition to other
      laboratory investigations, in order to evaluate its role in sero-epidemiological
      surveys. FINDINGS: A total of 210 cases were selected for the study. One hundred
      clinically and parasitologically confirmed cases were corroborated with other
      hematological profiles. The formol-gel test was included along with well matched
      control group comprising of normal endemic controls (50), non-endemic normals
      (20) and other febrile cases (40). All groups were tested by rK39 strip test.
      Fifty Kala azar cases were followed up after completion of successful treatment.
      They were subjected to rK39 strip test after 0, 90 and 180 days of completion of
      successful treatment.The rK39 showed sensitivity, specificity, PPV, NPV, and
      diagnostic accuracy of 98% (95% CI 91.7-100), 100%, 100%, 90% (95% CI 66-100) and
      98% (95% CI 92.6-100) respectively. All the 50 cured followed up cases showed
      positive result by rK39 strip test even after 180 days of completion of
      successful treatment. CONCLUSION: The test seems an ideal qualitative test for
      the diagnosis of kala-azar. But for sero-epidemiological studies the test may be
      used with other parameters. Alternatively a quantitative ELISA using rK39 antigen
      may be used.

PMID- 19772617
TI  - Presumed consent for organ preservation in uncontrolled donation after cardiac
      death in the United States: a public policy with serious consequences.
AB  - Organ donation after cessation of circulation and respiration, both controlled
      and uncontrolled, has been proposed by the Institute of Medicine as a way to
      increase opportunities for organ procurement. Despite claims to the contrary,
      both forms of controlled and uncontrolled donation after cardiac death raise
      significant ethical and legal issues. Identified causes for concern include
      absence of agreement on criteria for the declaration of death, nonexistence of
      universal guidelines for duration before stopping resuscitation efforts and
      techniques, and assumption of presumed intent to donate for the purpose of
      initiating temporary organ-preservation interventions when no expressed consent
      to donate is present. From a legal point of view, not having scientifically valid
      criteria of cessation of circulation and respiration for declaring death could
      lead to a conclusion that organ procurement itself is the proximate cause of
      death. Although the revised Uniform Anatomical Gift Act of 2006 provides broad
      immunity to those involved in organ-procurement activities, courts have yet to
      provide an opinion on whether persons can be held liable for injuries arising
      from the determination of death itself. Preserving organs in uncontrolled
      donation after cardiac death requires the administration of life-support systems
      such as extracorporeal membrane oxygenation. These life-support systems can lead
      to return of signs of life that, in turn, have to be deliberately suppressed by
      the administration of pharmacological agents. Finally, allowing temporary organ
      preservation interventions without expressed consent is inherently a violation of
      the principle of respect for a person's autonomy. Proponents of organ donation
      from uncontrolled donation after cardiac death, on the other hand, claim that
      these nonconsensual interventions enhance respect for autonomy by allowing
      people, through surrogate decision making, to execute their right to donate
      organs. However, the lack of transparency and the absence of protection of
      individual autonomy, for the sake of maximizing procurement opportunities, have
      placed the current organ-donation system of opting-in in great jeopardy. Equally
      as important, current policies enabling and enhancing organ procurement
      practices, pose challenges to the constitutional rights of individuals in a
      pluralistic society as these policies are founded on flawed medical standards for
      declaring death.

PMID- 19772618
TI  - Y-27632 enhances differentiation of blastocyst like cystic human embryoid bodies
      to endocrinologically active trophoblast cells on a biomimetic platform.
AB  - Trophoblast differentiation and formation of the placenta are important events
      linked to post-implantation embryonic development. Models mimicking the biology
      of trophoblast differentiation in a post-implantation maternal microenvironment
      are needed for understanding disorders like placental-ischemia or for
      applications in drug-screening, and would help in overcoming the ethical impasse
      on using human embryos for such research. Here we attempt to create such a model
      by using embryoid bodies (EBs) and a biomimetic platform composed of a bilayer of
      fibronectin and gelatin on top of low-melting agarose. Using this model we test
      the hypothesis that cystic-EBs (day 30) that resemble blastocysts
      morphologically, are better sources as compared to noncytic EBs (day 10), for
      functional trophoblast differentiation; and that the Rho kinases inhibitor Y27632
      can enhance this differentiation. Non/cytic EBs with/out Y27632 were grown on
      this platform for 28 days, and screened from secretion and expression of
      trophoblast and other lineage markers using ECLIA, RT-PCR, and
      Immunofluorescence. All EBs attached on this surface and rapidly proliferated
      into hCG and progesterone (P2) secreting functional trophoblast cells. However,
      the cells derived from cytic-EBs and cytic-EBs+ Y27632 showed the maximum
      secretion of these hormones and expressed IGF2, supporting our hypothesis. Also
      Y27632 reduced extraembryonic endoderm and trophoblast lineage differentiation
      from early noncystic-EBs, whereas, it specifically enhanced the induction of
      trophoblast and multinucleated syncitiotrophoblast differentiation from late
      cystic-EBs. In vivo trophoblast differentiation can be replicated in fibronectin
      based biomaterials, using cytic-EBs and by maneuvering the Rho-ROCK pathways.
      Response of EBs to a compound may vary temporally, and determination of their
      right stage is crucial for applications in directed-differentiation or drug
      screening.

PMID- 19772619
TI  - The first step in the development of Text Mining technology for Cancer Risk
      Assessment: identifying and organizing scientific evidence in risk assessment
      literature.
AB  - BACKGROUND: One of the most neglected areas of biomedical Text Mining (TM) is the
      development of systems based on carefully assessed user needs. We have recently
      investigated the user needs of an important task yet to be tackled by TM --
      Cancer Risk Assessment (CRA). Here we take the first step towards the development
      of TM technology for the task: identifying and organizing the scientific evidence
      required for CRA in a taxonomy which is capable of supporting extensive data
      gathering from biomedical literature. RESULTS: The taxonomy is based on expert
      annotation of 1297 abstracts downloaded from relevant PubMed journals. It
      classifies 1742 unique keywords found in the corpus to 48 classes which specify
      core evidence required for CRA. We report promising results with inter-annotator
      agreement tests and automatic classification of PubMed abstracts to taxonomy
      classes. A simple user test is also reported in a near real-world CRA scenario
      which demonstrates along with other evaluation that the resources we have built
      are well-defined, accurate, and applicable in practice. CONCLUSION: We present
      our annotation guidelines and a tool which we have designed for expert annotation
      of PubMed abstracts. A corpus annotated for keywords and document relevance is
      also presented, along with the taxonomy which organizes the keywords into classes
      defining core evidence for CRA. As demonstrated by the evaluation, the materials
      we have constructed provide a good basis for classification of CRA literature
      along multiple dimensions. They can support current manual CRA as well as
      facilitate the development of an approach based on TM. We discuss extending the
      taxonomy further via manual and machine learning approaches and the subsequent
      steps required to develop TM technology for the needs of CRA.

PMID- 19772620
TI  - Characterization of the chromosomal inversion associated with the Koa mutation in
      the mouse revealed the cause of skeletal abnormalities.
AB  - BACKGROUND: Koala (Koa) is a dominant mutation in mice causing bushy muzzle and
      pinna, and is associated with a chromosomal inversion on the distal half of
      chromosome 15. To identify the gene responsible for the Koa phenotypes, we
      investigated phenotypes of Koa homozygous mice and determined the breakpoints of
      the inversion with a genetic method using recombination between two different
      chromosomal inversions. RESULTS: Skeletal preparation of Koa homozygotes showed
      marked deformity of the ribs and a wider skull with extended zygomatic arches, in
      addition to a general reduction in the lengths of long bones. They also had open
      eyelids at birth caused by a defect in the extension of eyelid anlagen during the
      embryonic stages. The proximal and distal breakpoints of the Koa inversion were
      determined to be 0.8-Mb distal to the Trsps1 gene and to 0.1-Mb distal to the
      Hoxc4 gene, respectively, as previously reported. The phenotypes of mice with the
      recombinant inverted chromosomes revealed the localization of the gene
      responsible the Koa phenotype in the vicinity of the proximal recombinant
      breakpoint. Expression of the Trsps1 gene in this region was significantly
      reduced in the Koa homozygous and heterozygous embryos. CONCLUSION: While no gene
      was disrupted by the chromosomal inversion, an association between the Koa
      phenotype and the proximal recombinant breakpoint, phenotypic similarities with
      Trps1-deficient mice or human patients with TRSP1 mutations, and the reduced
      expression of the Trsps1 gene in Koa mice, indicated that the phenotypes of the
      Koa mice are caused by the altered expression of the Trps1 gene.

PMID- 19772622
TI  - The Schnauzenorgan-response of Gnathonemus petersii.
AB  - BACKGROUND: Electric fish navigate and explore their dark and turbid environment
      with a specialised electric sense. This active electrolocation involves the
      generation and perception of an electric signal and fish have proven to be useful
      model systems for the investigation of sensory-motor interactions. A well studied
      example is the elephantnose fish, Gnathonemus petersii, which has a
      characteristic and unique elongated chin covered with hundreds of electroreceptor
      organs. This highly moveable so-called Schnauzenorgan constitutes the main fovea
      of the active electrosensory system. Here we present first evidence for a sensory
      motor loop relating active electrical sensing to active motor exploration of the
      environment. RESULTS: Both anatomical and behavioural evidence have shown that
      the moveable Schnauzenorgan is crucial for prey localization. Here we show for
      the first time that a motor response (Schnauzenorgan-response, SOR) can be
      elicited by novel electrosensory stimuli. The SOR could be triggered with highest
      reliability by novel electrical stimuli near the Schnauzenorgan and, to a lesser
      extend, near the head of the animal. The probability of evoking the response
      depended on the magnitude of the amplitude change of the electric input, with
      bigger changes eliciting SORs more reliably. Similarly, increasing the distance
      of the stimulus reduced the response. In this respect the SOR is comparable to
      the well described novelty response, a transient acceleration of the production
      rate of electric signals, although the latter occurs at a shorter delay and can
      also be evoked by non-electrical stimuli. CONCLUSION: Our experiments show a
      novel motor response that is mediated by the active electric sense of Gnathonemus
      petersii. This response will allow a detailed analysis of the neural system
      underlying direct interaction between sensory and motor processes in future
      experiments.

PMID- 19772621
TI  - Cardiac-surgery associated acute kidney injury requiring renal replacement
      therapy. A Spanish retrospective case-cohort study.
AB  - BACKGROUND: Acute kidney injury is among the most serious complications after
      cardiac surgery and is associated with an impaired outcome. Multiple factors may
      concur in the development of this disease. Moreover, severe renal failure
      requiring renal replacement therapy (RRT) presents a high mortality rate.
      Consequently, we studied a Spanish cohort of patients to assess the risk factors
      for RRT in cardiac surgery-associated acute kidney injury (CSA-AKI). METHODS: A
      retrospective case-cohort study in 24 Spanish hospitals. All cases of RRT after
      cardiac surgery in 2007 were matched in a crude ratio of 1:4 consecutive patients
      based on age, sex, treated in the same year, at the same hospital and by the same
      group of surgeons. RESULTS: We analyzed the data from 864 patients enrolled in
      2007. In multivariate analysis, severe acute kidney injury requiring
      postoperative RRT was significantly associated with the following variables:
      lower glomerular filtration rates, less basal haemoglobin, lower left ventricular
      ejection fraction, diabetes, prior diuretic treatment, urgent surgery, longer
      aortic cross clamp times, intraoperative administration of aprotinin, and
      increased number of packed red blood cells (PRBC) transfused. When we conducted a
      propensity analysis using best-matched of 137 available pairs of patients, prior
      diuretic treatment, longer aortic cross clamp times and number of PRBC transfused
      were significantly associated with CSA-AKI.Patients requiring RRT needed longer
      hospital stays, and suffered higher mortality rates. CONCLUSION: Cardiac-surgery
      associated acute kidney injury requiring RRT is associated with worse outcomes.
      For this reason, modifiable risk factors should be optimised and higher risk
      patients for acute kidney injury should be identified before undertaking cardiac
      surgery.

PMID- 19772623
TI  - Mirrors in the PDB: left-handed alpha-turns guide design with D-amino acids.
AB  - BACKGROUND: Incorporating variable amino acid stereochemistry in molecular design
      has the potential to improve existing protein stability and create new topologies
      inaccessible to homochiral molecules. The Protein Data Bank has been a reliable,
      rich source of information on molecular interactions and their role in protein
      stability and structure. D-amino acids rarely occur naturally, making it
      difficult to infer general rules for how they would be tolerated in proteins
      through an analysis of existing protein structures. However, protein elements
      containing short left-handed turns and helices turn out to contain useful
      information. Molecular mechanisms used in proteins to stabilize left-handed
      elements by L-amino acids are structurally enantiomeric to potential synthetic
      strategies for stabilizing right-handed elements with D-amino acids. RESULTS:
      Propensities for amino acids to occur in contiguous alpha(L) helices correlate
      with published thermodynamic scales for incorporation of D-amino acids into
      alpha(R) helices. Two backbone rules for terminating a left-handed helix are
      found: an alpha(R) conformation is disfavored at the amino terminus, and a
      beta(R) conformation is disfavored at the carboxy terminus. Helix capping
      sidechain-backbone interactions are found which are unique to alpha(L) helices
      including an elevated propensity for L-Asn, and L-Thr at the amino terminus and L
      Gln, L-Thr and L-Ser at the carboxy terminus. CONCLUSION: By examining left
      handed alpha-turns containing L-amino acids, new interaction motifs for
      incorporating D-amino acids into right-handed alpha-helices are identified. These
      will provide a basis for de novo design of novel heterochiral protein folds.

PMID- 19772624
TI  - Genotypic comparison of Pantoea agglomerans plant and clinical strains.
AB  - BACKGROUND: Pantoea agglomerans strains are among the most promising biocontrol
      agents for a variety of bacterial and fungal plant diseases, particularly fire
      blight of apple and pear. However, commercial registration of P. agglomerans
      biocontrol products is hampered because this species is currently listed as a
      biosafety level 2 (BL2) organism due to clinical reports as an opportunistic
      human pathogen. This study compares plant-origin and clinical strains in a search
      for discriminating genotypic/phenotypic markers using multi-locus phylogenetic
      analysis and fluorescent amplified fragment length polymorphisms (fAFLP)
      fingerprinting. RESULTS: Majority of the clinical isolates from culture
      collections were found to be improperly designated as P. agglomerans after
      sequence analysis. The frequent taxonomic rearrangements underwent by the
      Enterobacter agglomerans/Erwinia herbicola complex may be a major problem in
      assessing clinical associations within P. agglomerans. In the P. agglomerans
      sensu stricto (in the stricter sense) group, there was no discrete clustering of
      clinical/biocontrol strains and no marker was identified that was uniquely
      associated to clinical strains. A putative biocontrol-specific fAFLP marker was
      identified only in biocontrol strains. The partial ORF located in this band
      corresponded to an ABC transporter that was found in all P. agglomerans strains.
      CONCLUSION: Taxonomic mischaracterization was identified as a major problem with
      P. agglomerans, and current techniques removed a majority of clinical strains
      from this species. Although clear discrimination between P. agglomerans plant and
      clinical strains was not obtained with phylogenetic analysis, a single marker
      characteristic of biocontrol strains was identified which may be of use in strain
      biosafety determinations. In addition, the lack of Koch's postulate fulfilment,
      rare retention of clinical strains for subsequent confirmation, and the
      polymicrobial nature of P. agglomerans clinical reports should be considered in
      biosafety assessment of beneficial strains in this species.

PMID- 19772625
TI  - A new integrative weaning index of discontinuation from mechanical ventilation.
AB  - INTRODUCTION: Indexes predicting weaning outcome are frequently inaccurate. We
      developed a new integrative weaning index aimed at improving the accuracy of the
      traditional indexes. METHODS: Three hundred and thirty-one patients mechanically
      ventilated for more than 24 hours were evaluated. Initially, the threshold values
      of each index that best discriminate between a successful and an unsuccessful
      weaning outcome were determined in 115 patients. In the second phase, the
      predictive performance of these values was tested prospectively in the other 216
      patients. Frequency/tidal volume ratio (f/Vt ratio), tidal volume (Vt), tracheal
      airway occlusion pressure 0.1 s (P 0.1), the product of P 0.1 and f/Vt (P 0.1 x
      f/Vt), respiratory rate (f), static compliance of the respiratory system
      (Cst,rs), ratio of arterial oxygen tension to fraction of inspired oxygen
      (PaO2/FiO2 ratio) and the new integrative weaning index IWI (Cst,rs x arterial
      oxygen saturation/f/Vt ratio) were evaluated in all patients. The readiness for
      weaning and the decision to return to mechanical ventilation was made by the
      physician in charge, based on the signs of poor tolerance. The receiver operating
      characteristic (ROC) curves were calculated in order to evaluate the predictive
      performance of each index. The Bayes' theorem was used to assess the probability
      of each test of predicting weaning. RESULTS: In the prospective-validation set,
      successful weaning was observed in 183 patients (84.7%) and weaning failure in 33
      (15.27%). IWI presented the highest accuracy, with the area under the ROC curves
      larger than that under the curves for the f/Vt ratio (0.96 x 0.85 respectively; P
      = 0.003), and also larger than that under the curves for the other indexes. IWI
      presented a higher probability of successful weaning when the test was positive
      (0.99) and a lower probability when the test was negative (0.14). Measurement of
      Cst,rs during the weaning process was considered one of the study limitations.
      CONCLUSIONS: IWI was the best predictive performance index of weaning outcome and
      can be used in the intensive care unit setting. TRIAL REGISTRATION: controlled
      trials.com ISRCTN92117906.

PMID- 19772626
TI  - MicroarrayDesigner: an online search tool and repository for near-optimal
      microarray experimental designs.
AB  - BACKGROUND: Dual-channel microarray experiments are commonly employed for
      inference of differential gene expressions across varying organisms and
      experimental conditions. The design of dual-channel microarray experiments that
      can help minimize the errors in the resulting inferences has recently received
      increasing attention. However, a general and scalable search tool and a
      corresponding database of optimal designs were still missing. DESCRIPTION: An
      efficient and scalable search method for finding near-optimal dual-channel
      microarray designs, based on a greedy hill-climbing optimization strategy, has
      been developed. It is empirically shown that this method can successfully and
      efficiently find near-optimal designs. Additionally, an improved interwoven loop
      design construction algorithm has been developed to provide an easily computable
      general class of near-optimal designs. Finally, in order to make the best results
      readily available to biologists, a continuously evolving catalog of near-optimal
      designs is provided. CONCLUSION: A new search algorithm and database for near
      optimal microarray designs have been developed. The search tool and the database
      are accessible via the World Wide Web at http://db.cse.ohio
      state.edu/MicroarrayDesigner. Source code and binary distributions are available
      for academic use upon request.

PMID- 19772628
TI  - Geographic information system (GIS) maps and malaria control monitoring:
      intervention coverage and health outcome in distal villages of Khammouane
      province, Laos.
AB  - BACKGROUND: Insecticide-treated nets (ITNs) are a key intervention to control
      malaria. The intervention coverage varies as a consequence of geographical
      accessibility to remote villages and limitations of financial and human resources
      for the intervention. People's adherence to the intervention, i.e., proper use of
      ITNs, also affects malaria health outcome. The study objective is to explore the
      impact of the intervention coverage and people's adherence to the intervention on
      malaria health outcome among targeted villages in various geographic locations.
      METHODS: Geographic information system (GIS) maps were developed using the data
      collected in an active case detection survey in Khammouane province, Laos. The
      survey was conducted using rapid diagnostic tests (RDTs) and a structured
      questionnaire at 23 sites in the province from June to July, the rainy season, in
      2005. A total of 1,711 villagers from 403 households participated in the survey.
      RESULTS: As indicated on the GIS maps, villages with malaria cases, lower
      intervention coverage, and lower adherence were identified. Although no malaria
      case was detected in most villages with the best access to the district center,
      several cases were detected in the distal villages, where the intervention
      coverage and adherence to the intervention remained relatively lower. CONCLUSION:
      Based on the data and maps, it was demonstrated that malaria remained unevenly
      distributed within districts. Balancing the intervention coverage in the distal
      villages with the overall coverage and continued promotion of the proper use of
      ITNs are necessary for a further reduction of malaria cases in the province.

PMID- 19772627
TI  - Large A-fiber activity is required for microglial proliferation and p38 MAPK
      activation in the spinal cord: different effects of resiniferatoxin and
      bupivacaine on spinal microglial changes after spared nerve injury.
AB  - BACKGROUND: After peripheral nerve injury, spontaneous ectopic activity arising
      from the peripheral axons plays an important role in inducing central
      sensitization and neuropathic pain. Recent evidence indicates that activation of
      spinal cord microglia also contributes to the development of neuropathic pain. In
      particular, activation of p38 mitogen-activated protein kinase (MAPK) in spinal
      microglia is required for the development of mechanical allodynia. However,
      activity-dependent activation of microglia after nerve injury has not been fully
      addressed. To determine whether spontaneous activity from C- or A-fibers is
      required for microglial activation, we used resiniferatoxin (RTX) to block the
      conduction of transient receptor potential vanilloid subtype 1 (TRPV1) positive
      fibers (mostly C- and Adelta-fibers) and bupivacaine microspheres to block all
      fibers of the sciatic nerve in rats before spared nerve injury (SNI), and
      observed spinal microglial changes 2 days later. RESULTS: SNI induced robust
      mechanical allodynia and p38 activation in spinal microglia. SNI also induced
      marked cell proliferation in the spinal cord, and all the proliferating cells
      (BrdU+) were microglia (Iba1+). Bupivacaine induced a complete sensory and motor
      blockade and also significantly inhibited p38 activation and microglial
      proliferation in the spinal cord. In contrast, and although it produced an
      efficient nociceptive block, RTX failed to inhibit p38 activation and microglial
      proliferation in the spinal cord. CONCLUSION: (1) Blocking peripheral input in
      TRPV1-positive fibers (presumably C-fibers) is not enough to prevent nerve injury
      induced spinal microglial activation. (2) Peripheral input from large myelinated
      fibers is important for microglial activation. (3) Microglial activation is
      associated with mechanical allodynia.

PMID- 19772630
TI  - Presence of Helicobacter pylori in betel chewers and non betel chewers with and
      without oral cancers.
AB  - BACKGROUND: Betel chewing has been shown to predispose to periodontal disease and
      oral cancer. Studies show that people with gum disease are more likely to test
      positive for Helicobacter pylori (H. pylori). It is not known if the lesions
      produced by betel quid and the resulting, chemical changes predispose to
      colonization by H. pylori. Further the role of this organism in oral cancer is
      not known. Our objective was to determine the presence of H. pylori in oral
      lesions of thirty oral cancer patients and to determine the presence of IgG
      antibodies to H. pylori in oral cancer patients who are betel chewers and non
      betel chewers, healthy betel chewers and healthy non-betel chewers and to compare
      the presence of H. pylori in these four groups. This case control study was
      conducted at the Cancer Institute Maharagama and the Department of Microbiology,
      Faculty of Medical Sciences, University of Sri Jayewardenepura. METHODS: One
      hundred and seventy three subjects, of whom fifty three were patients presenting
      with oral cancer to the Cancer Institute Maharagama, sixty healthy betel chewers
      and sixty healthy non-betel chewers from the Religious and Welfare Service Centre
      Maharagama were tested for H. pylori by serology. Thirty oral biopsies from oral
      cancer patients were cultured under microaerophilic condition to isolate H.
      pylori. The statistic used was Chi-square test. RESULTS: Of the fifty-three oral
      cancer patients, forty-four were betel chewers. Among the 53 oral cancer patients
      examined, ten of forty-four (10/44 = 22.7%) patients who are betel chewers and
      four of nine (4/9 = 44.4%) patients who are non-betel chewers were detected
      positive for IgG antibody against H. pylori. In the healthy group (betel chewers
      and non betel chewers) ten (16.7%) of the healthy betel chewers tested positive
      for H. pylori by serology. None of the healthy non-betel chewers tested positive
      for H. pyloriFourteen [26.4%] of oral cancer patients tested positive for H.
      pylori by serology, of which two were also culture positive (Only thirty samples
      were cultured). The presence of H. pylori in betel chewers (with or without
      cancer) compared to non-betel chewers was statistically significant. (Chi-square
      test p < 0.05) The use of tobacco and areca nut in betel chewers was significant
      with the presence of H. pylori (p < 0.05). CONCLUSION: There is a significant
      higher proportion of H. pylori in betel chewers compared to non-betel chewers but
      not between oral cancer patients compared to patients without oral cancer. Hence
      Betel chewing may predispose to colonisation with H. pylori in the digestive
      tract through swallowing the quid or during betel chewing.

PMID- 19772631
TI  - Modeling system states in liver cells: survival, apoptosis and their
      modifications in response to viral infection.
AB  - BACKGROUND: The decision pro- or contra apoptosis is complex, involves a number
      of different inputs, and is central for the homeostasis of an individual cell as
      well as for the maintenance and regeneration of the complete organism. RESULTS:
      This study centers on Fas ligand (FasL)-mediated apoptosis, and a complex and
      internally strongly linked network is assembled around the central FasL-mediated
      apoptosis cascade. Different bioinformatical techniques are employed and
      different crosstalk possibilities including the integrin pathway are considered.
      This network is translated into a Boolean network (74 nodes, 108 edges). System
      stability is dynamically sampled and investigated using the software SQUAD.
      Testing a number of alternative crosstalk possibilities and networks we find that
      there are four stable system states, two states comprising cell survival and two
      states describing apoptosis by the intrinsic and the extrinsic pathways,
      respectively. The model is validated by comparing it to experimental data from
      kinetics of cytochrome c release and caspase activation in wildtype and Bid
      knockout cells grown on different substrates. Pathophysiological modifications
      such as input from cytomegalovirus proteins M36 and M45 again produces output
      behavior that well agrees with experimental data. CONCLUSION: A network model for
      apoptosis and crosstalk in hepatocytes shows four different system states and
      reproduces a number of different conditions around apoptosis including effects of
      different growth substrates and viral infections. It produces semi-quantitative
      predictions on the activity of individual nodes, agreeing with experimental data.
      The model (SBML format) and all data are available for further predictions and
      development.

PMID- 19772633
TI  - From sequence to dynamics: the effects of transcription factor and polymerase
      concentration changes on activated and repressed promoters.
AB  - BACKGROUND: The fine tuning of two features of the bacterial regulatory machinery
      have been known to contribute to the diversity of gene expression within the same
      regulon: the sequence of Transcription Factor (TF) binding sites, and their
      location with respect to promoters. While variations of binding sequences
      modulate the strength of the interaction between the TF and its binding sites,
      the distance between binding sites and promoters alter the interaction between
      the TF and the RNA polymerase (RNAP). RESULTS: In this paper we estimated the
      dissociation constants (K(d)) of several E. coli TFs in their interaction with
      variants of their binding sequences from the scores resulting from aligning them
      to Positional Weight Matrices. A correlation coefficient of 0.78 was obtained
      when pooling together sites for different TFs. The theoretically estimated K(d)
      values were then used, together with the dissociation constants of the RNAP
      promoter interaction to analyze activated and repressed promoters. The strength
      of repressor sites -- i.e., the strength of the interaction between TFs and their
      binding sites -- is slightly higher than that of activated sites. We explored how
      different factors such as the variation of binding sequences, the occurrence of
      more than one binding site, or different RNAP concentrations may influence the
      promoters' response to the variations of TF concentrations. We found that the
      occurrence of several regulatory sites bound by the same TF close to a promoter -
      if they are bound by the TF in an independent manner -- changes the effect of TF
      concentrations on promoter occupancy, with respect to individual sites. We also
      found that the occupancy of a promoter will never be more than half if the RNAP
      concentration-to-K(p) ratio is 1 and the promoter is subject to repression; or
      less than half if the promoter is subject to activation. If the ratio falls to
      0.1, the upper limit of occupancy probability for repressed drops below 10%; a
      descent of the limits occurs also for activated promoters. CONCLUSION: The number
      of regulatory sites may thus act as a versatility-producing device, in addition
      to serving as a source of robustness of the transcription machinery. Furthermore,
      our results show that the effects of TF concentration fluctuations on promoter
      occupancy are constrained by RNAP concentrations.

PMID- 19772632
TI  - Biological versus chronological ovarian age: implications for assisted
      reproductive technology.
AB  - BACKGROUND: Women have been able to delay childbearing since effective
      contraception became available in the 1960s. However, fertility decreases with
      increasing maternal age. A slow but steady decrease in fertility is observed in
      women aged between 30 and 35 years, which is followed by an accelerated decline
      among women aged over 35 years. A combination of delayed childbearing and reduced
      fecundity with increasing age has resulted in an increased number and proportion
      of women of greater than or equal to 35 years of age seeking assisted
      reproductive technology (ART) treatment. METHODS: Literature searches
      supplemented with the authors' knowledge. RESULTS: Despite major advances in
      medical technology, there is currently no ART treatment strategy that can fully
      compensate for the natural decline in fertility with increasing female age.
      Although chronological age is the most important predictor of ovarian response to
      follicle-stimulating hormone, the rate of reproductive ageing and ovarian
      sensitivity to gonadotrophins varies considerably among individuals. Both
      environmental and genetic factors contribute to depletion of the ovarian oocyte
      pool and reduction in oocyte quality. Thus, biological and chronological ovarian
      age are not always equivalent. Furthermore, biological age is more important than
      chronological age in predicting the outcome of ART. As older patients present
      increasingly for ART treatment, it will become more important to critically
      assess prognosis, counsel appropriately and optimize treatment strategies.
      Several genetic markers and biomarkers (such as anti-Mullerian hormone and the
      antral follicle count) are emerging that can identify women with accelerated
      biological ovarian ageing. Potential strategies for improving ovarian response
      include the use of luteinizing hormone (LH) and growth hormone (GH). When
      endogenous LH levels are heavily suppressed by gonadotrophin-releasing hormone
      analogues, LH supplementation may help to optimize treatment outcomes for women
      with biologically older ovaries. Exogenous GH may improve oocyte development and
      counteract the age-related decline of oocyte quality. The effects of GH may be
      mediated by insulin-like growth factor-I, which works synergistically with
      follicle-stimulating hormone on granulosa and theca cells. CONCLUSION: Patients
      with biologically older ovaries may benefit from a tailored approach based on
      individual patient characteristics. Among the most promising adjuvant therapies
      for improving ART outcomes in women of advanced reproductive age are the
      administration of exogenous LH or GH.

PMID- 19772629
TI  - Genomewide association study for onset age in Parkinson disease.
AB  - BACKGROUND: Age at onset in Parkinson disease (PD) is a highly heritable
      quantitative trait for which a significant genetic influence is supported by
      multiple segregation analyses. Because genes associated with onset age may
      represent invaluable therapeutic targets to delay the disease, we sought to
      identify such genetic modifiers using a genomewide association study in familial
      PD. There have been previous genomewide association studies (GWAS) to identify
      genes influencing PD susceptibility, but this is the first to identify genes
      contributing to the variation in onset age. METHODS: Initial analyses were
      performed using genotypes generated with the Illumina HumanCNV370Duo array in a
      sample of 857 unrelated, familial PD cases. Subsequently, a meta-analysis of
      imputed SNPs was performed combining the familial PD data with that from a
      previous GWAS of 440 idiopathic PD cases. The SNPs from the meta-analysis with
      the lowest p-values and consistency in the direction of effect for onset age were
      then genotyped in a replication sample of 747 idiopathic PD cases from the
      Parkinson Institute Biobank of Milan, Italy. RESULTS: Meta-analysis across the
      three studies detected consistent association (p < 1 x 10(-5)) with five SNPs,
      none of which reached genomewide significance. On chromosome 11, the SNP with the
      lowest p-value (rs10767971; p = 5.4 x 10(-7)) lies between the genes QSER1 and
      PRRG4. Near the PARK3 linkage region on chromosome 2p13, association was observed
      with a SNP (rs7577851; p = 8.7 x 10(-6)) which lies in an intron of the AAK1
      gene. This gene is closely related to GAK, identified as a possible PD
      susceptibility gene in the GWAS of the familial PD cases. CONCLUSION: Taken
      together, these results suggest an influence of genes involved in endocytosis and
      lysosomal sorting in PD pathogenesis.

PMID- 19772634
TI  - NMDA receptor subunit expression and PAR2 receptor activation in colospinal
      afferent neurons (CANs) during inflammation induced visceral hypersensitivity.
AB  - BACKGROUND: Visceral hypersensitivity is a clinical observation made when
      diagnosing patients with functional bowel disorders. The cause of visceral
      hypersensitivity is unknown but is thought to be attributed to inflammation.
      Previously we demonstrated that a unique set of enteric neurons, colospinal
      afferent neurons (CANs), co-localize with the NR1 and NR2D subunits of the NMDA
      receptor as well as with the PAR2 receptor. The aim of this study was to
      determine if NMDA and PAR2 receptors expressed on CANs contribute to visceral
      hypersensitivity following inflammation. Recently, work has suggested that dorsal
      root ganglion (DRG) neurons expressing the transient receptor potential vanilloid
      1 (TRPV1) receptor mediate inflammation induced visceral hypersensitivity.
      Therefore, in order to study CAN involvement in visceral hypersensitivity, DRG
      neurons expressing the TRPV1 receptor were lesioned with resiniferatoxin (RTX)
      prior to inflammation and behavioural testing. RESULTS: CANs do not express the
      TRPV1 receptor; therefore, they survive following RTX injection. RTX treatment
      resulted in a significant decrease in TRPV1 expressing neurons in the colon and
      immunohistochemical analysis revealed no change in peptide or receptor expression
      in CANs following RTX lesioning as compared to control data. Behavioral studies
      determined that both inflamed non-RTX and RTX animals showed a decrease in
      balloon pressure threshold as compared to controls. Immunohistochemical analysis
      demonstrated that the NR1 cassettes, N1 and C1, of the NMDA receptor on CANs were
      up-regulated following inflammation. Furthermore, inflammation resulted in the
      activation of the PAR2 receptors expressed on CANs. CONCLUSION: Our data show
      that inflammation causes an up-regulation of the NMDA receptor and the activation
      of the PAR2 receptor expressed on CANs. These changes are associated with a
      decrease in balloon pressure in response to colorectal distension in non-RTX and
      RTX lesioned animals. Therefore, these data suggest that CANs contribute to
      visceral hypersensitivity during inflammation.

PMID- 19772635
TI  - A systematic review of longitudinal studies on the association between depression
      and smoking in adolescents.
AB  - BACKGROUND: It is well-established that smoking and depression are associated in
      adolescents, but the temporal ordering of the association is subject to debate.
      METHODS: Longitudinal studies in English language which reported the onset of
      smoking on depression in non clinical populations (age 13-19) published between
      January 1990 and July 2008 were selected from PubMed, OVID, and PsychInfo
      databases. Study characteristics were extracted. Meta-analytic pooling procedures
      with random effects were used. RESULTS: Fifteen studies were retained for
      analysis. The pooled estimate for smoking predicting depression in 6 studies was
      1.73 (95% CI: 1.32, 2.40; p < 0.001). The pooled estimate for depression
      predicting smoking in 12 studies was 1.41 (95% CI: 1.21, 1.63; p < 0.001).
      Studies that used clinical measures of depression were more likely to report a
      bidirectional effect, with a stronger effect of depression predicting smoking.
      CONCLUSION: Evidence from longitudinal studies suggests that the association
      between smoking and depression is bidirectional. To better estimate these
      effects, future research should consider the potential utility of: (a) shorter
      intervals between surveys with longer follow-up time, (b) more accurate
      measurement of depression, and (c) adequate control of confounding.

PMID- 19772636
TI  - Genes encoding novel secreted and transmembrane proteins are temporally and
      spatially regulated during Drosophila melanogaster embryogenesis.
AB  - BACKGROUND: Morphogenetic events that shape the Drosophila melanogaster embryo
      are tightly controlled by a genetic program in which specific sets of genes are
      up-regulated. We used a suppressive subtractive hybridization procedure to
      identify a group of developmentally regulated genes during early stages of D.
      melanogaster embryogenesis. We studied the spatiotemporal activity of these genes
      in five different intervals covering 12 stages of embryogenesis. RESULTS:
      Microarrays were constructed to confirm induction of expression and to determine
      the temporal profile of isolated subtracted cDNAs during embryo development. We
      identified a set of 118 genes whose expression levels increased significantly in
      at least one developmental interval compared with a reference interval. Of these
      genes, 53% had a phenotype and/or molecular function reported in the literature,
      whereas 47% were essentially uncharacterized. Clustering analysis revealed
      demarcated transcript groups with maximum gene activity at distinct developmental
      intervals. In situ hybridization assays were carried out on 23 uncharacterized
      genes, 15 of which proved to have spatiotemporally restricted expression
      patterns. Among these 15 uncharacterized genes, 13 were found to encode putative
      secreted and transmembrane proteins. For three of them we validated our protein
      sequence predictions by expressing their cDNAs in Drosophila S2R+ cells and
      analyzed the subcellular distribution of recombinant proteins. We then focused on
      the functional characterization of the gene CG6234. Inhibition of CG6234 by RNA
      interference resulted in morphological defects in embryos, suggesting the
      involvement of this gene in germ band retraction. CONCLUSION: Our data have
      yielded a list of developmentally regulated D. melanogaster genes and their
      expression profiles during embryogenesis and provide new information on the
      spatiotemporal expression patterns of several uncharacterized genes. In
      particular, we recovered a substantial number of unknown genes encoding putative
      secreted and transmembrane proteins, suggesting new components of signaling
      pathways that might be incorporated within the existing regulatory networks
      controlling D. melanogaster embryogenesis. These genes are also good candidates
      for additional targeted functional analyses similar to those we conducted for
      CG6234.See related minireview by Vichas and Zallen:
      http://www.jbiol.com/content/8/8/76.

PMID- 19772637
TI  - Genome-scale comparison and constraint-based metabolic reconstruction of the
      facultative anaerobic Fe(III)-reducer Rhodoferax ferrireducens.
AB  - BACKGROUND: Rhodoferax ferrireducens is a metabolically versatile, Fe(III)
      reducing, subsurface microorganism that is likely to play an important role in
      the carbon and metal cycles in the subsurface. It also has the unique ability to
      convert sugars to electricity, oxidizing the sugars to carbon dioxide with
      quantitative electron transfer to graphite electrodes in microbial fuel cells. In
      order to expand our limited knowledge about R. ferrireducens, the complete genome
      sequence of this organism was further annotated and then the physiology of R.
      ferrireducens was investigated with a constraint-based, genome-scale in silico
      metabolic model and laboratory studies. RESULTS: The iterative modeling and
      experimental approach unveiled exciting, previously unknown physiological
      features, including an expanded range of substrates that support growth, such as
      cellobiose and citrate, and provided additional insights into important features
      such as the stoichiometry of the electron transport chain and the ability to grow
      via fumarate dismutation. Further analysis explained why R. ferrireducens is
      unable to grow via photosynthesis or fermentation of sugars like other members of
      this genus and uncovered novel genes for benzoate metabolism. The genome also
      revealed that R. ferrireducens is well-adapted for growth in the subsurface
      because it appears to be capable of dealing with a number of environmental
      insults, including heavy metals, aromatic compounds, nutrient limitation and
      oxidative stress. CONCLUSION: This study demonstrates that combining genome-scale
      modeling with the annotation of a new genome sequence can guide experimental
      studies and accelerate the understanding of the physiology of under-studied yet
      environmentally relevant microorganisms.

PMID- 19772639
TI  - Identifying primary care patients at risk for future diabetes and cardiovascular
      disease using electronic health records.
AB  - BACKGROUND: Prevention of diabetes and coronary heart disease (CHD) is possible
      but identification of at-risk patients for targeting interventions is a challenge
      in primary care. METHODS: We analyzed electronic health record (EHR) data for
      122,715 patients from 12 primary care practices. We defined patients with risk
      factor clustering using metabolic syndrome (MetS) characteristics defined by NCEP
      ATPIII criteria; if missing, we used surrogate characteristics, and validated
      this approach by directly measuring risk factors in a subset of 154 patients. For
      subjects with at least 3 of 5 MetS criteria measured at baseline (2003-2004), we
      defined 3 categories: No MetS (0 criteria); At-risk-for MetS (1-2 criteria); and
      MetS (>or= 3 criteria). We examined new diabetes and CHD incidence, and resource
      utilization over the subsequent 3-year period (2005-2007) using age-sex-adjusted
      regression models to compare outcomes by MetS category. RESULTS: After excluding
      patients with diabetes/CHD at baseline, 78,293 patients were eligible for
      analysis. EHR-defined MetS had 73% sensitivity and 91% specificity for directly
      measured MetS. Diabetes incidence was 1.4% in No MetS; 4.0% in At-risk-for MetS;
      and 11.0% in MetS (p < 0.0001 for trend; adjusted OR MetS vs No MetS = 6.86 [6.06
      7.76]); CHD incidence was 3.2%, 5.3%, and 6.4% respectively (p < 0.0001 for
      trend; adjusted OR = 1.42 [1.25-1.62]). Costs and resource utilization increased
      across categories (p < 0.0001 for trends). Results were similar analyzing
      individuals with all five criteria not missing, or defining MetS as >or= 2
      criteria present. CONCLUSION: Risk factor clustering in EHR data identifies
      primary care patients at increased risk for new diabetes, CHD and higher resource
      utilization.

PMID- 19772638
TI  - Monitoring compartment-specific substrate cleavage by cathepsins B, K, L, and S
      at physiological pH and redox conditions.
AB  - BACKGROUND: Cysteine cathepsins are known to primarily cleave their substrates at
      reducing and acidic conditions within endo-lysosomes. Nevertheless, they have
      also been linked to extracellular proteolysis, that is, in oxidizing and neutral
      environments. Although the impact of reducing or oxidizing conditions on
      proteolytic activity is a key to understand physiological protease functions,
      redox conditions have only rarely been considered in routine enzyme activity
      assays. Therefore we developed an assay to test for proteolytic processing of a
      natural substrate by cysteine cathepsins which accounts for redox potentials and
      pH values corresponding to the conditions in the extracellular space in
      comparison to those within endo-lysosomes of mammalian cells. RESULTS: The
      proteolytic potencies of cysteine cathepsins B, K, L and S towards thyroglobulin
      were analyzed under conditions simulating oxidizing versus reducing environments
      with neutral to acidic pH values. Thyroglobulin, the precursor molecule of
      thyroid hormones, was chosen as substrate, because it represents a natural target
      of cysteine cathepsins. Thyroglobulin processing involves thyroid hormone
      liberation which, under physiological circumstances, starts in the extracellular
      follicle lumen before being continued within endo-lysosomes. Our study shows that
      all cathepsins tested were capable of processing thyroglobulin at neutral and
      oxidizing conditions, although these are reportedly non-favorable for cysteine
      proteases. All analyzed cathepsins generated distinct fragments of thyroglobulin
      at extracellular versus endo-lysosomal conditions as demonstrated by SDS-PAGE
      followed by immunoblotting or N-terminal sequencing. Moreover, the thyroid
      hormone thyroxine was liberated by the action of cathepsin S at extracellular
      conditions, while cathepsins B, K and L worked most efficiently in this respect
      at endo-lysosomal conditions. CONCLUSION: The results revealed distinct cleavage
      patterns at all conditions analyzed, indicating compartment-specific processing
      of thyroglobulin by cysteine cathepsins. In particular, proteolytic activity of
      cathepsin S towards the substrate thyroglobulin can now be understood as
      instrumental for extracellular thyroid hormone liberation. Our study emphasizes
      that the proteolytic functions of cysteine cathepsins in the thyroid are not
      restricted to endo-lysosomes but include pivotal roles in extracellular substrate
      utilization. We conclude that understanding of the interplay and fine adjustment
      of protease networks in vivo is better approachable by simulating physiological
      conditions in protease activity assays.

PMID- 19772640
TI  - Transcription factor Sp1 induces ADAM17 and contributes to tumor cell
      invasiveness under hypoxia.
AB  - BACKGROUND: Expression of the Sp1 transcription factor is induced by hypoxia, and
      the ADAM17 promoter contains predicted Sp1 binding sites. ADAM17 contributes to
      hypoxic-induce invasiveness of glioma. In this study, we investigated whether Sp1
      transcription factor induces ADAM17 and/or contributes to tumor cell invasiveness
      in hypoxia. METHODS: Employing RT-PCR and Western blot, we examined the role of
      Sp1 in ADAM17 transcription/expression under normoxic and hypoxic conditions, and
      whether it binds to the ADAM17 GC-rich promoter region using a chromatin
      immunoprecipitation assay. Additionally, we tested the effect of Sp1 suppression
      in tumor cell invasion and migration, using Matrigel basement membrane invasion
      chambers, a scratch wound-healing assay, and small interfering RNA. RESULTS:
      Here, we found that Sp1 binds to the ADAM17 promoter, and that Sp1 regulates
      ADAM17 expression under hypoxia. Furthermore, suppression of Sp1 decreases
      invasiveness and migration in U87 tumor cells. CONCLUSION: Our findings suggest
      the Sp1 transcription factor mediates ADAM17 expression under hypoxia, regulates
      glioma invasiveness, and thus, may be a target for anti-invasion therapies.

PMID- 19772641
TI  - Spatially uniform relieff (SURF) for computationally-efficient filtering of gene
      gene interactions.
AB  - BACKGROUND: Genome-wide association studies are becoming the de facto standard in
      the genetic analysis of common human diseases. Given the complexity and
      robustness of biological networks such diseases are unlikely to be the result of
      single points of failure but instead likely arise from the joint failure of two
      or more interacting components. The hope in genome-wide screens is that these
      points of failure can be linked to single nucleotide polymorphisms (SNPs) which
      confer disease susceptibility. Detecting interacting variants that lead to
      disease in the absence of single-gene effects is difficult however, and methods
      to exhaustively analyze sets of these variants for interactions are combinatorial
      in nature thus making them computationally infeasible. Efficient algorithms which
      can detect interacting SNPs are needed. ReliefF is one such promising algorithm,
      although it has low success rate for noisy datasets when the interaction effect
      is small. ReliefF has been paired with an iterative approach, Tuned ReliefF
      (TuRF), which improves the estimation of weights in noisy data but does not
      fundamentally change the underlying ReliefF algorithm. To improve the sensitivity
      of studies using these methods to detect small effects we introduce Spatially
      Uniform ReliefF (SURF). RESULTS: SURF's ability to detect interactions in this
      domain is significantly greater than that of ReliefF. Similarly SURF, in
      combination with the TuRF strategy significantly outperforms TuRF alone for SNP
      selection under an epistasis model. It is important to note that this success
      rate increase does not require an increase in algorithmic complexity and allows
      for increased success rate, even with the removal of a nuisance parameter from
      the algorithm. CONCLUSION: Researchers performing genetic association studies and
      aiming to discover gene-gene interactions associated with increased disease
      susceptibility should use SURF in place of ReliefF. For instance, SURF should be
      used instead of ReliefF to filter a dataset before an exhaustive MDR analysis.
      This change increases the ability of a study to detect gene-gene interactions.
      The SURF algorithm is implemented in the open source Multifactor Dimensionality
      Reduction (MDR) software package available from http://www.epistasis.org.

PMID- 19772642
TI  - Intra-individual polymorphism in diploid and apomictic polyploid hawkweeds
      (Hieracium, Lactuceae, Asteraceae): disentangling phylogenetic signal,
      reticulation, and noise.
AB  - BACKGROUND: Hieracium s.str. is a complex species-rich group of perennial herbs
      composed of few sexual diploids and numerous apomictic polyploids. The existence
      of reticulation and the near-continuity of morphological characters across taxa
      seriously affect species determination, making Hieracium one of the best examples
      of a 'botanist's nightmare'. Consequently, its species relationships have not
      previously been addressed by molecular methods. Concentrating on the supposed
      major evolutionary units, we used nuclear ribosomal (ETS) and chloroplast (trnT
      trnL) sequences in order to disentangle the phylogenetic relationships and to
      infer the origins of the polyploids. RESULTS: Despite relatively low
      interspecific variation, the nuclear data revealed the existence of two major
      groups roughly corresponding to species with a Western or Eastern European
      origin. Extensive reticulation was mainly inferred from the character additivity
      of parental ETS variants. Surprisingly, many diploid species were of hybrid
      origin whilst several polyploid taxa showed no evidence of reticulation. Intra
      individual ETS sequence polymorphism generally exceeded interspecific variation
      and was either independent of, or additional to, additive patterns accounted for
      by hybrid origin. Several ETS ribotypes occurred in different hybrid taxa, but
      never as the only variant in any species analyzed. CONCLUSION: The high level of
      intra-individual ETS polymorphism prevented straightforward phylogenetic
      analysis. Characterization of this variation as additive, shared informative,
      homoplasious, or unique made it possible to uncover the phylogenetic signal and
      to reveal the hybrid origin of 29 out of 60 accessions. Contrary to expectation,
      diploid sexuals and polyploid apomicts did not differ in their molecular
      patterns. The basic division of the genus into two major clades had not
      previously been intimated on morphological grounds. Both major groups are thought
      to have survived in different glacial refugia and to have hybridized as a result
      of secondary contact. Several lines of evidence suggest the data is best
      explained by the presence of an extinct range of variation and a larger diversity
      of ancestral diploids in former times rather than by unsampled variation. Extinct
      diversity and extensive reticulation are thought to have largely obscured the
      species relationships. Our study illustrates how multigene sequences can be used
      to disentangle the evolutionary history of agamic complexes or similarly
      difficult datasets.

PMID- 19772645
TI  - Early results of coronary artery bypass grafting with coronary endarterectomy for
      severe coronary artery disease.
AB  - BACKGROUND: Despite the existence of controversial debates on the efficiency of
      coronary endarterectomy (CE), it is still used as an adjunct to coronary artery
      bypass grafting (CABG). This is particularly true in patients with endstage
      coronary artery disease. Given the improvements in cardiac surgery and
      postoperative care, as well as the rising number of elderly patient with numerous
      co-morbidities, re-evaluating the pros and cons of this technique is needed.
      METHODS: Patient demographic information, operative details and outcome data of
      104 patients with diffuse calcified coronary artery disease were retrospectively
      analyzed with respect to functional capacity (NYHA), angina pectoris (CCS) and
      mortality. Actuarial survival was reported using a Kaplan-Meyer analysis.
      RESULTS: Between August 2001 and March 2005, 104 patients underwent coronary
      artery bypass grafting (CABG) with adjunctive coronary endarterectomy (CE) in the
      Department of Thoracic-, Cardiac- and Vascular Surgery, University of Goettingen.
      Four patients were lost during follow-up. Data were gained from 88 male and 12
      female patients; mean age was 65.5 +/- 9 years. A total of 396 vessels were
      bypassed (4 +/- 0.9 vessels per patient). In 98% left internal thoracic artery
      (LITA) was used as arterial bypass graft and a total of 114 vessels were
      endarterectomized. CE was performed on right coronary artery (RCA) (n = 55), on
      left anterior descending artery (LAD) (n = 52) and circumflex artery (RCX) (n =
      7). Ninety-five patients suffered from 3-vessel-disease, 3 from 2-vessel- and 2
      from 1-vessel-disease. Closed technique was used in 18%, open technique in 79%
      and in 3% a combination of both. The most frequent endarterectomized localization
      was right coronary artery (RCA = 55%). Despite the severity of endstage
      atherosclerosis, hospital mortality was only 5% (n = 5). During follow-up (24.5
      +/- 13.4 months), which is 96% complete (4 patients were lost caused by unknown
      address) 8 patients died (cardiac failure: 3; stroke: 1; cancer: 1; unknown
      reasons: 3). NYHA-classification significantly improved after CABG with CE from
      2.2 +/- 0.9 preoperative to 1.7 +/- 0.9 postoperative. CCS also changed from 2.4
      +/- 1.0 to 1.5 +/- 0.8 CONCLUSION: Early results of coronary endarterectomy are
      acceptable with respect to mortality, NYHA & CCS. This technique offers a
      valuable surgical option for patients with endstage coronary artery disease in
      whom complete revascularization otherwise can not be obtained. Careful patient
      selection will be necessary to assure the long-term benefit of this procedure.

PMID- 19772643
TI  - Nociception-induced spatial and temporal plasticity of synaptic connection and
      function in the hippocampal formation of rats: a multi-electrode array recording.
AB  - BACKGROUND: Pain is known to be processed by a complex neural network
      (neuromatrix) in the brain. It is hypothesized that under pathological state,
      persistent or chronic pain can affect various higher brain functions through
      ascending pathways, leading to co-morbidities or mental disability of pain.
      However, so far the influences of pathological pain on the higher brain functions
      are less clear and this may hinder the advances in pain therapy. In the current
      study, we studied spatiotemporal plasticity of synaptic connection and function
      in the hippocampal formation (HF) in response to persistent nociception. RESULTS:
      On the hippocampal slices of rats which had suffered from persistent nociception
      for 2 h by receiving subcutaneous bee venom (BV) or formalin injection into one
      hand paw, multisite recordings were performed by an 8 x 8 multi-electrode array
      probe. The waveform of the field excitatory postsynaptic potential (fEPSP),
      induced by perforant path electrical stimulation and pharmacologically identified
      as being activity-dependent and mediated by ionotropic glutamate receptors, was
      consistently positive-going in the dentate gyrus (DG), while that in the CA1 was
      negative-going in shape in naive and saline control groups. For the spatial
      characteristics of synaptic plasticity, BV- or formalin-induced persistent pain
      significantly increased the number of detectable fEPSP in both DG and CA1 area,
      implicating enlargement of the synaptic connection size by the injury or acute
      inflammation. Moreover, the input-output function of synaptic efficacy was shown
      to be distinctly enhanced by the injury with the stimulus-response curve being
      moved leftward compared to the control. For the temporal plasticity, long-term
      potentiation produced by theta burst stimulation (TBS) conditioning was also
      remarkably enhanced by pain. Moreover, it is strikingly noted that the shape of
      fEPSP waveform was drastically deformed or split by a TBS conditioning under the
      condition of persistent nociception, while that in naive or saline control state
      was not affected. All these changes in synaptic connection and function,
      confirmed by the 2-dimentional current source density imaging, were found to be
      highly correlated with peripheral persistent nociception since pre-blockade of
      nociceptive impulses could eliminate all of them. Finally, the initial
      pharmacological investigation showed that AMPA/KA glutamate receptors might play
      more important roles in mediation of pain-associated spatiotemporal plasticity
      than NMDA receptors. CONCLUSION: Peripheral persistent nociception produces great
      impact upon the higher brain structures that lead to not only temporal
      plasticity, but also spatial plasticity of synaptic connection and function in
      the HF. The spatial plasticity of synaptic activities is more complex than the
      temporal plasticity, comprising of enlargement of synaptic connection size at
      network level, deformed fEPSP at local circuit level and, increased synaptic
      efficacy at cellular level. In addition, the multi-synaptic model established in
      the present investigation may open a new avenue for future studies of pain
      related brain dysfunctions at the higher level of the neuromatrix.

PMID- 19772646
TI  - Strategies for analyzing highly enriched IP-chip datasets.
AB  - BACKGROUND: Chromatin immunoprecipitation on tiling arrays (ChIP-chip) has been
      employed to examine features such as protein binding and histone modifications on
      a genome-wide scale in a variety of cell types. Array data from the latter
      studies typically have a high proportion of enriched probes whose signals vary
      considerably (due to heterogeneity in the cell population), and this makes their
      normalization and downstream analysis difficult. RESULTS: Here we present
      strategies for analyzing such experiments, focusing our discussion on the
      analysis of Bromodeoxyruridine (BrdU) immunoprecipitation on tiling array (BrdU
      IP-chip) datasets. BrdU-IP-chip experiments map large, recently replicated
      genomic regions and have similar characteristics to histone modification/location
      data. To prepare such data for downstream analysis we employ a dynamic
      programming algorithm that identifies a set of putative unenriched probes, which
      we use for both within-array and between-array normalization. We also introduce a
      second dynamic programming algorithm that incorporates a priori knowledge to
      identify and quantify positive signals in these datasets. CONCLUSION: Highly
      enriched IP-chip datasets are often difficult to analyze with traditional array
      normalization and analysis strategies. Here we present and test a set of
      analytical tools for their normalization and quantification that allows for
      accurate identification and analysis of enriched regions.

PMID- 19772644
TI  - An overview of cardiovascular risk factor burden in sub-Saharan African
      countries: a socio-cultural perspective.
AB  - BACKGROUND: Sub-Saharan African (SSA) countries are currently experiencing one of
      the most rapid epidemiological transitions characterized by increasing
      urbanization and changing lifestyle factors. This has resulted in an increase in
      the incidence of non-communicable diseases, especially cardiovascular disease
      (CVD). This double burden of communicable and chronic non-communicable diseases
      has long-term public health impact as it undermines healthcare systems. PURPOSE:
      The purpose of this paper is to explore the socio-cultural context of CVD risk
      prevention and treatment in sub-Saharan Africa. We discuss risk factors specific
      to the SSA context, including poverty, urbanization, developing healthcare
      systems, traditional healing, lifestyle and socio-cultural factors. METHODOLOGY:
      We conducted a search on African Journals On-Line, Medline, PubMed, and PsycINFO
      databases using combinations of the key country/geographic terms, disease and
      risk factor specific terms such as "diabetes and Congo" and "hypertension and
      Nigeria". Research articles on clinical trials were excluded from this overview.
      Contrarily, articles that reported prevalence and incidence data on CVD risk
      and/or articles that report on CVD risk-related beliefs and behaviors were
      included. Both qualitative and quantitative articles were included. RESULTS: The
      epidemic of CVD in SSA is driven by multiple factors working collectively.
      Lifestyle factors such as diet, exercise and smoking contribute to the increasing
      rates of CVD in SSA. Some lifestyle factors are considered gendered in that some
      are salient for women and others for men. For instance, obesity is a predominant
      risk factor for women compared to men, but smoking still remains mostly a risk
      factor for men. Additionally, structural and system level issues such as lack of
      infrastructure for healthcare, urbanization, poverty and lack of government
      programs also drive this epidemic and hampers proper prevention, surveillance and
      treatment efforts. CONCLUSION: Using an African-centered cultural framework, the
      PEN3 model, we explore future directions and efforts to address the epidemic of
      CVD risk in SSA.

PMID- 19772647
TI  - Grand challenges for biological engineering.
AB  - Biological engineering will play a significant role in solving many of the
      world's problems in medicine, agriculture, and the environment. Recently the U.S.
      National Academy of Engineering (NAE) released a document "Grand Challenges in
      Engineering," covering broad realms of human concern from sustainability, health,
      vulnerability and the joy of living. Biological engineers, having tools and
      techniques at the interface between living and non-living entities, will play a
      prominent role in forging a better future. The 2010 Institute of Biological
      Engineering (IBE) conference in Cambridge, MA, USA will address, in part, the
      roles of biological engineering in solving the challenges presented by the NAE.
      This letter presents a brief outline of how biological engineers are working to
      solve these large scale and integrated problems of our society.

PMID- 19772649
TI  - Augmentation of tibial plateau fractures with Trabecular Metal: a biomechanical
      study.
AB  - BACKGROUND: Restoration and maintenance of the plateau surface are the key points
      in the treatment of tibial plateau fractures. Any deformity of the articular
      surface jeopardizes the future of the knee by causing osteoarthritis and axis
      deviation. The purpose of this study is to evaluate the effect of Trabecular
      Metal (porous tantalum metal) on stability and strength of fracture repair in the
      central depression tibial plateau fracture. METHOD: Six matched pairs of fresh
      frozen human cadaveric tibias were fractured and randomly assigned to be treated
      with either the standard of treatment (impacted cancellous bone graft stabilized
      by two 4.5 mm screws under the comminuted articular surface) or the experimental
      method (the same screws supporting a 2 cm diameter Trabecular Metal (TM) disc
      placed under the comminuted articular surface). Each tibia was tested on a MTS
      machine simulating immediate postoperative load transmission with 500 Newton for
      10,000 cycles and then loaded to failure to determine the ultimate strength of
      the construct. RESULTS: The trabecular metal construct showed 40% less caudad
      displacement of the articular surface (1, 32 +/- 0.1 mm vs. 0, 80 +/- 0.1 mm) in
      cyclic loading (p < 0.05). Its mechanical failure occurred at a mean of 3275 N
      compared to 2650 N for the standard of care construct (p < 0, 05). CONCLUSION:
      The current study shows the biomechanical superiority of the trabecular metal
      construct compared to the current standard of treatment with regards to both its
      resistance to caudad displacement of the articular surface in cyclic loading and
      its strength at load to failure.

PMID- 19772648
TI  - Characterization of WRKY co-regulatory networks in rice and Arabidopsis.
AB  - BACKGROUND: The WRKY transcription factor gene family has a very ancient origin
      and has undergone extensive duplications in the plant kingdom. Several studies
      have pointed out their involvement in a range of biological processes, revealing
      that a large number of WRKY genes are transcriptionally regulated under
      conditions of biotic and/or abiotic stress. To investigate the existence of WRKY
      co-regulatory networks in plants, a whole gene family WRKYs expression study was
      carried out in rice (Oryza sativa). This analysis was extended to Arabidopsis
      thaliana taking advantage of an extensive repository of gene expression data.
      RESULTS: The presented results suggested that 24 members of the rice WRKY gene
      family (22% of the total) were differentially-regulated in response to at least
      one of the stress conditions tested. We defined the existence of nine OsWRKY gene
      clusters comprising both phylogenetically related and unrelated genes that were
      significantly co-expressed, suggesting that specific sets of WRKY genes might act
      in co-regulatory networks. This hypothesis was tested by Pearson Correlation
      Coefficient analysis of the Arabidopsis WRKY gene family in a large set of
      Affymetrix microarray experiments. AtWRKYs were found to belong to two main co
      regulatory networks (COR-A, COR-B) and two smaller ones (COR-C and COR-D), all
      including genes belonging to distinct phylogenetic groups. The COR-A network
      contained several AtWRKY genes known to be involved mostly in response to
      pathogens, whose physical and/or genetic interaction was experimentally proven.
      We also showed that specific co-regulatory networks were conserved between the
      two model species by identifying Arabidopsis orthologs of the co-expressed OsWRKY
      genes. CONCLUSION: In this work we identified sets of co-expressed WRKY genes in
      both rice and Arabidopsis that are functionally likely to cooperate in the same
      signal transduction pathways. We propose that, making use of data from co
      regulatory networks, it is possible to highlight novel clusters of plant genes
      contributing to the same biological processes or signal transduction pathways.
      Our approach will contribute to unveil gene cooperation pathways not yet
      identified by classical genetic analyses. This information will open new routes
      contributing to the dissection of WRKY signal transduction pathways in plants.

PMID- 19772650
TI  - Surveillance of the short-term impact of fine particle air pollution on
      cardiovascular disease hospitalizations in New York State.
AB  - BACKGROUND: Studies have shown that the effects of particulate matter on health
      vary based on factors including the vulnerability of the population, health care
      practices, exposure factors, and the pollutant mix. METHODS: We used time
      stratified case-crossover to estimate differences in the short-term impacts of
      PM2.5 on cardiovascular disease hospital admissions in New York State by
      geographic area, year, age, gender, co-morbid conditions, and area poverty rates.
      RESULTS: PM2.5 had a stronger impact on heart failure than other cardiovascular
      diagnoses, with 3.1% of heart failure admissions attributable to short-term PM2.5
      exposure over background levels of 5 ug/m3. Older adults were significantly more
      susceptible to heart failure after short-term ambient PM2.5 exposure than younger
      adults. CONCLUSION: The short-term impact of PM2.5 on cardiovascular disease
      admissions, and modifications of that impact, are small and difficult to measure
      with precision. Multi-state collaborations will be necessary to attain more
      precision to describe spatiotemporal differences in health impacts.

PMID- 19772651
TI  - Isolation and functional characterization of cold-regulated promoters, by
      digitally identifying peach fruit cold-induced genes from a large EST dataset.
AB  - BACKGROUND: Cold acclimation is the process by which plants adapt to the low, non
      freezing temperatures that naturally occur during late autumn or early winter.
      This process enables the plants to resist the freezing temperatures of winter.
      Temperatures similar to those associated with cold acclimation are also used by
      the fruit industry to delay fruit ripening in peaches. However, peaches that are
      subjected to long periods of cold storage may develop chilling injury symptoms
      (woolliness and internal breakdown). In order to better understand the
      relationship between cold acclimation and chilling injury in peaches, we isolated
      and functionally characterized cold-regulated promoters from cold-inducible genes
      identified by digitally analyzing a large EST dataset. RESULTS: Digital
      expression analyses of EST datasets, revealed 164 cold-induced peach genes,
      several of which show similarities to genes associated with cold acclimation and
      cold stress responses. The promoters of three of these cold-inducible genes
      (Ppbec1, Ppxero2 and Pptha1) were fused to the GUS reporter gene and
      characterized for cold-inducibility using both transient transformation assays in
      peach fruits (in fruta) and stable transformation in Arabidopsis thaliana. These
      assays demonstrate that the promoter Pptha1 is not cold-inducible, whereas the
      Ppbec1 and Ppxero2 promoter constructs are cold-inducible. CONCLUSION: This work
      demonstrates that during cold storage, peach fruits differentially express genes
      that are associated with cold acclimation. Functional characterization of these
      promoters in transient transformation assays in fruta as well as stable
      transformation in Arabidopsis, demonstrate that the isolated Ppbec1 and Ppxero2
      promoters are cold-inducible promoters, whereas the isolated Pptha1 promoter is
      not cold-inducible. Additionally, the cold-inducible activity of the Ppbec1 and
      Ppxero2 promoters suggest that there is a conserved heterologous cold-inducible
      regulation of these promoters in peach and Arabidopsis. These results reveal that
      digital expression analyses may be used in non-model species to identify
      candidate genes whose promoters are differentially expressed in response to
      exogenous stimuli.

PMID- 19772652
TI  - Development of a theoretical framework for analyzing cerebrospinal fluid
      dynamics.
AB  - BACKGROUND: To date hydrocephalus researchers acknowledge the need for rigorous
      but utilitarian fluid mechanics understanding and methodologies in studying
      normal and hydrocephalic intracranial dynamics. Pressure volume models and
      electric circuit analogs introduced pressure into volume conservation; but
      control volume analysis enforces independent conditions on pressure and volume.
      Previously, utilization of clinical measurements has been limited to
      understanding of the relative amplitude and timing of flow, volume and pressure
      waveforms; qualitative approaches without a clear framework for meaningful
      quantitative comparison. METHODS: Control volume analysis is presented to
      introduce the reader to the theoretical background of this foundational fluid
      mechanics technique for application to general control volumes. This approach is
      able to directly incorporate the diverse measurements obtained by clinicians to
      better elucidate intracranial dynamics and progression to disorder. RESULTS:
      Several examples of meaningful intracranial control volumes and the particular
      measurement sets needed for the analysis are discussed. CONCLUSION: Control
      volume analysis provides a framework to guide the type and location of
      measurements and also a way to interpret the resulting data within a fundamental
      fluid physics analysis.

PMID- 19772653
TI  - Biochemical analysis of CTLA-4 immunoreactive material from human blood.
AB  - BACKGROUND: CTLA-4 was initially described as a membrane-bound molecule that
      inhibited lymphocyte activation by interacting with B7.1 and B7.2 molecules on
      antigen presenting cells. Alternative splicing of mRNA encoding the CTLA-4
      receptor leads to the production of a molecule (sCTLA-4) that lacks a membrane
      anchor and is therefore secreted into the extracellular space. Despite studies
      finding that people with autoimmune disease more frequently express high levels
      of sCTLA-4 in their blood than apparently healthy people, the significance of
      these findings is unclear. METHODS: Molecules isolated from blood using CTLA-4
      specific antibodies were analyzed with ligand binding assays, mass spectroscopy,
      and biochemical fractionation in an effort to increase our understanding of CTLA
      4 immunoreactive material. RESULTS: Mass spectroscopy analysis of the molecules
      recognized by multiple CTLA-4-specific antibodies failed to identify any CTLA-4
      protein. Even though these molecules bind to the CTLA-4 receptors B7.1 and B7.2,
      they also exhibit properties common to immunoglobulins. CONCLUSION: We have
      identified molecules in blood that are recognized by CTLA-4 specific antibodies
      but also exhibit properties of immunoglobulins. Our data indicates that what has
      been called sCTLA-4 is not a direct product of the CTLA-4 gene, and that the CTLA
      4 protein is not part of this molecule. These results may explain why the
      relationship of sCTLA-4 to immune system activity has been difficult to
      elucidate.

PMID- 19772654
TI  - A methodology for the analysis of differential coexpression across the human
      lifespan.
AB  - BACKGROUND: Differential coexpression is a change in coexpression between genes
      that may reflect 'rewiring' of transcriptional networks. It has previously been
      hypothesized that such changes might be occurring over time in the lifespan of an
      organism. While both coexpression and differential expression of genes have been
      previously studied in life stage change or aging, differential coexpression has
      not. Generalizing differential coexpression analysis to many time points presents
      a methodological challenge. Here we introduce a method for analyzing changes in
      coexpression across multiple ordered groups (e.g., over time) and extensively
      test its validity and usefulness. RESULTS: Our method is based on the use of the
      Haar basis set to efficiently represent changes in coexpression at multiple time
      scales, and thus represents a principled and generalizable extension of the idea
      of differential coexpression to life stage data. We used published microarray
      studies categorized by age to test the methodology. We validated the methodology
      by testing our ability to reconstruct Gene Ontology (GO) categories using our
      measure of differential coexpression and compared this result to using
      coexpression alone. Our method allows significant improvement in characterizing
      these groups of genes. Further, we examine the statistical properties of our
      measure of differential coexpression and establish that the results are
      significant both statistically and by an improvement in semantic similarity. In
      addition, we found that our method finds more significant changes in gene
      relationships compared to several other methods of expressing temporal
      relationships between genes, such as coexpression over time. CONCLUSION:
      Differential coexpression over age generates significant and biologically
      relevant information about the genes producing it. Our Haar basis methodology for
      determining age-related differential coexpression performs better than other
      tested methods. The Haar basis set also lends itself to ready interpretation in
      terms of both evolutionary and physiological mechanisms of aging and can be seen
      as a natural generalization of two-category differential coexpression. CONTACT:
      paul@bioinformatics.ubc.ca.

PMID- 19772655
TI  - Genetic association study of selected candidate genes (ApoB, LPL, Leptin) and
      telomere length in obese and hypertensive individuals.
AB  - BACKGROUND: A genetic study was carried out among obese and hypertensive
      individuals from India to assess allelic association, if any, at three candidate
      loci: Apolipoprotein B (ApoB) minisatellite and two tetranucleotide repeat loci;
      LPL (Lipoprotein lipase) and Leptin. Attempt has also been made to find out
      whether telomere length attrition is associated with hypertension and obese
      individuals. METHODS: Venous blood samples were collected from 37 normal, 35
      obese and 47 hypertensive individuals. Genomic DNA was extracted from peripheral
      blood mononuclear cells (PBMC) and PCR amplifications were achieved using locus
      specific primers. Genotyping of ApoB minisatellite was performed using 4%
      polyacrylamide gel electrophoresis (PAGE) followed by silver staining, whereas
      LPL and Leptin loci were genotyped using ALF Express DNA sequencer. Telomere
      length was determined using a recently developed real time based quantitative
      PCR, where the relative telomere length was determined by calculating the
      relative ratio of telomere (T) and single copy gene (S) PCR products which is
      expressed as T/S ratio. RESULTS: All the three loci are highly polymorphic,
      display high heterozygosity and conform to Hardy-Weinberg's equilibrium
      expectations. ApoB minisatellite displayed 14 alleles, whereas LPL and Leptin
      tetranucleotide loci were having 9 and 17 alleles, respectively. Interestingly
      two new alleles (9 and 11 repeats) were detected at ApoB locus for the first
      time. The alleles at Leptin locus were classified as Class I (lower alleles: 149
      200 bp) and Class II alleles (higher alleles: >217 bp). Higher alleles at ApoB
      (>39 repeats), predominant allele 9 at LPL and alleles 164 bp and 224 bp at
      Leptin loci have shown allelic association with hypertensive individuals. After
      adjusting the influence of age and gender, the analysis of co-variance (ANCOVA)
      revealed the relative telomere length (T/S ratio) in hypertensive individuals to
      be (1.01 +/- 0.021), which was significantly different (P < 0.001) from obese
      (1.20 +/- 0.023) and normal (1.22 +/- 0.014) individuals. However, no significant
      difference in the relative telomere length was observed among male and female
      individuals, although age related decrease in telomere length was observed in
      these limited sample size. CONCLUSION: The present study revealed that allelic
      association at ApoB, LPL, Leptin loci and loss of telomere length may have strong
      genetic association with hypertensive individuals. However, further study on
      larger sample size is needed to draw firm conclusions.

PMID- 19772656
TI  - Serratus muscle stimulation effectively treats notalgia paresthetica caused by
      long thoracic nerve dysfunction: a case series.
AB  - Currently, notalgia paresthetica (NP) is a poorly-understood condition diagnosed
      on the basis of pruritus, pain, or both, in the area medial to the scapula and
      lateral to the thoracic spine. It has been proposed that NP is caused by
      degenerative changes to the T2-T6 vertebrae, genetic disposition, or nerve
      entrapment of the posterior rami of spinal nerves arising at T2-T6. Despite
      considerable research, the etiology of NP remains unclear, and a multitude of
      different treatment modalities have correspondingly met with varying degrees of
      success. Here we demonstrate that NP can be caused by long thoracic nerve injury
      leading to serratus anterior dysfunction, and that electrical muscle stimulation
      (EMS) of the serratus anterior can successfully and conservatively treat NP. In
      four cases of NP with known injury to the long thoracic nerve we performed
      transcutaneous EMS to the serratus anterior in an area far lateral to the site of
      pain and pruritus, resulting in significant and rapid pain relief. These findings
      are the first to identify long thoracic nerve injury as a cause for notalgia
      paresthetica and electrical muscle stimulation of the serratus anterior as a
      possible treatment, and we discuss the implications of these findings on better
      diagnosing and treating notalgia paresthetica.

PMID- 19772657
TI  - The epidemiology and factors associated with nocturnal enuresis among boarding
      and daytime school children in southeast of Turkey: a cross sectional study.
AB  - BACKGROUND: Nocturnal enuresis is an important problem among young children
      living in Turkey. The purpose of this study was to determine the possible
      differences in the prevalence of enuresis between children in boarding school and
      daytime school and the association of enuresis with sociodemographic factors.
      METHODS: This was a cross-sectional survey. A total of 562 self-administered
      questionnaires were distributed to parents from two different types of schools.
      One of them was a day-time school and the other was a boarding school. To
      describe enuresis the ICD-10 definition of at least one wet night per month for
      three consecutive months was used. Chi-square test and a logistic regression
      model was used to identify significant predictive factors for enuresis. RESULTS:
      The overall prevalence of nocturnal enuresis was 14.9%. The prevalence of
      nocturnal enuresis declined with age. Of the 6 year old children 33.3% still
      wetted their beds, while the ratio was 2.6% for 15 years-olds. There was no
      significant difference in prevalence of nocturnal enuresis between boys and girls
      (14.3% versus 16. 8%). Enuresis was reported as 18.5% among children attending
      day time school and among those 11.5% attending boarding school (p < 0.05).
      Prevalence of enuresis was increased in children living in villages, with low
      income and with positive family history (p < 0.05). After multivariate analysis,
      history of urinary tract infection (OR = 2.02), age (OR = 1.28), low monthly
      income (OR = 2.86) and family history of enuresis (OR = 3.64) were factors
      associated with enuresis. 46.4% of parents and 57.1% of enuretic children were
      significantly concerned about the impact of enuresis. CONCLUSION: Enuresis was
      more frequent among children attending daytime school when compared to boarding
      school. Our findings suggest that nocturnal enuresis is a common problem among
      school children, especially with low income, smaller age, family history of
      enuresis and history of urinary tract infection. Enuresis is a pediatric public
      health problem and efforts at all levels should be made such as preventive,
      etiological and curative.

PMID- 19772659
TI  - Juvenile pleomorphic adenoma of the cheek: a case report and review of
      literature.
AB  - Pleomorphic adenoma, also called benign mixed tumor, is the most common tumor of
      the salivary glands. About 90% of these tumors occur in the parotid gland and 10%
      in the minor salivary glands. The most common sites of pleomorphic adenoma of the
      minor salivary glands are the palates followed by lips and cheeks. Other rare
      sites include the throat, floor of the mouth, tongue, tonsil, pharynx, retromolar
      area and nasal cavity. In children, intraoral pleomorphic adenomas of the cheek
      are extremely rare with only three cases reported to date. Here we report a case
      of pleomorphic adenoma of minor salivary glands of the cheek in a 17-year-old
      girl. The mass was removed by wide local excision with adequate margins, and
      after a follow-up period of three years there were no recurrences. To conclude,
      pleomorphic adenoma should be considered in the differential diagnosis of cheek
      masses in youngsters. Wide local excision is to be recommended as the treatment
      of choice. A close follow-up is necessary postoperatively.

PMID- 19772658
TI  - Exon expression in lymphoblastoid cell lines from subjects with schizophrenia
      before and after glucose deprivation.
AB  - BACKGROUND: The purpose of this study was to examine the effects of glucose
      reduction stress on lymphoblastic cell line (LCL) gene expression in subjects
      with schizophrenia compared to non-psychotic relatives. METHODS: LCLs were grown
      under two glucose conditions to measure the effects of glucose reduction stress
      on exon expression in subjects with schizophrenia compared to unaffected family
      member controls. A second aim of this project was to identify cis-regulated
      transcripts associated with diagnosis. RESULTS: There were a total of 122
      transcripts with significant diagnosis by probeset interaction effects and 328
      transcripts with glucose deprivation by probeset interaction probeset effects
      after corrections for multiple comparisons. There were 8 transcripts with
      expression significantly affected by the interaction between diagnosis and
      glucose deprivation and probeset after correction for multiple comparisons. The
      overall validation rate by qPCR of 13 diagnosis effect genes identified through
      microarray was 62%, and all genes tested by qPCR showed concordant up- or down
      regulation by qPCR and microarray. We assessed brain gene expression of five
      genes found to be altered by diagnosis and glucose deprivation in LCLs and found
      a significant decrease in expression of one gene, glutaminase, in the
      dorsolateral prefrontal cortex (DLPFC). One SNP with previously identified
      regulation by a 3' UTR SNP was found to influence IRF5 expression in both brain
      and lymphocytes. The relationship between the 3' UTR rs10954213 genotype and IRF5
      expression was significant in LCLs (p = 0.0001), DLPFC (p = 0.007), and anterior
      cingulate cortex (p = 0.002). CONCLUSION: Experimental manipulation of cells
      lines from subjects with schizophrenia may be a useful approach to explore stress
      related gene expression alterations in schizophrenia and to identify SNP variants
      associated with gene expression.

PMID- 19772660
TI  - Imaging short- and long-term training success in chronic aphasia.
AB  - BACKGROUND: To date, functional imaging studies of treatment-induced recovery
      from chronic aphasia only assessed short-term treatment effects after intensive
      language training. In the present study, we show with functional magnetic
      resonance imaging (fMRI), that different brain regions may be involved in
      immediate versus long-term success of intensive language training in chronic post
      stroke aphasia patients. RESULTS: Eight patients were trained daily for three
      hours over a period of two weeks in naming of concrete objects. Prior to,
      immediately after, and eight months after training, patients overtly named
      trained and untrained objects during event-related fMRI. On average the patients
      improved from zero (at baseline) to 64.4% correct naming responses immediately
      after training, and treatment success remained highly stable at follow-up.
      Regression analyses showed that the degree of short-term treatment success was
      predicted by increased activity (compared to the pretraining scan) bilaterally in
      the hippocampal formation, the right precuneus and cingulate gyrus, and
      bilaterally in the fusiform gyri. A different picture emerged for long-term
      training success, which was best predicted by activity increases in the right
      sided Wernicke's homologue and to a lesser degree in perilesional temporal areas.
      CONCLUSION: The results show for the first time that treatment-induced language
      recovery in the chronic stage after stroke is a dynamic process. Initially, brain
      regions involved in memory encoding, attention, and multimodal integration
      mediated treatment success. In contrast, long-term treatment success was
      predicted mainly by activity increases in the so-called 'classical' language
      regions. The results suggest that besides perilesional and homologue language
      associated regions, functional integrity of domain-unspecific memory structures
      may be a prerequisite for successful (intensive) language interventions.

PMID- 19772662
TI  - Integrating human stem cell expansion and neuronal differentiation in
      bioreactors.
AB  - BACKGROUND: Human stem cells are cellular resources with outstanding potential
      for cell therapy. However, for the fulfillment of this application, major
      challenges remain to be met. Of paramount importance is the development of robust
      systems for in vitro stem cell expansion and differentiation. In this work, we
      successfully developed an efficient scalable bioprocess for the fast production
      of human neurons. RESULTS: The expansion of undifferentiated human embryonal
      carcinoma stem cells (NTera2/cl.D1 cell line) as 3D-aggregates was firstly
      optimized in spinner vessel. The media exchange operation mode with an inoculum
      concentration of 4 x 10(5) cell/mL was the most efficient strategy tested, with a
      4.6-fold increase in cell concentration achieved in 5 days. These results were
      validated in a bioreactor where similar profile and metabolic performance were
      obtained. Furthermore, characterization of the expanded population by
      immunofluorescence microscopy and flow cytometry showed that NT2 cells maintained
      their stem cell characteristics along the bioreactor culture time.Finally, the
      neuronal differentiation step was integrated in the bioreactor process, by
      addition of retinoic acid when cells were in the middle of the exponential phase.
      Neurosphere composition was monitored and neuronal differentiation efficiency
      evaluated along the culture time. The results show that, for bioreactor cultures,
      we were able to increase significantly the neuronal differentiation efficiency by
      10-fold while reducing drastically, by 30%, the time required for the
      differentiation process. CONCLUSION: The culture systems developed herein are
      robust and represent one-step-forward towards the development of integrated
      bioprocesses, bridging stem cell expansion and differentiation in fully
      controlled bioreactors.

PMID- 19772661
TI  - Many LINE1 elements contribute to the transcriptome of human somatic cells.
AB  - BACKGROUND: While LINE1 (L1) retroelements comprise nearly 20% of the human
      genome, the majority are thought to have been rendered transcriptionally
      inactive, due to either mutation or epigenetic suppression. How many L1 elements
      'escape' these forms of repression and contribute to the transcriptome of human
      somatic cells? We have cloned out expressed sequence tags corresponding to the 5'
      and 3' flanks of L1 elements in order to characterize the population of elements
      that are being actively transcribed. We also examined expression of a select
      number of elements in different individuals. RESULTS: We isolated expressed
      sequence tags from human lymphoblastoid cell lines corresponding to 692 distinct
      L1 element sites, including 410 full-length elements. Four of the expression
      tagged sites corresponding to full-length elements from the human specific L1Hs
      subfamily were examined in European-American individuals and found to be
      differentially expressed in different family members. CONCLUSIONS: A large number
      of different L1 element sites are expressed in human somatic tissues, and this
      expression varies among different individuals. Paradoxically, few elements were
      tagged at high frequency, indicating that the majority of expressed L1s are
      transcribed at low levels. Based on our preliminary expression studies of a
      limited number of elements in a single family, we predict a significant degree of
      inter-individual transcript-level polymorphism in this class of sequence.

PMID- 19772663
TI  - Medication safety in acute care in Australia: where are we now? Part 2: a review
      of strategies and activities for improving medication safety 2002-2008.
AB  - BACKGROUND: This paper presents Part 2 of a literature review examining
      medication safety in the Australian acute care setting. This review was
      undertaken for the Australian Commission on Safety and Quality in Health Care,
      updating the 2002 national report on medication safety. Part 2 of the review
      examined the Australian evidence base for approaches to build safer medication
      systems in acute care. METHODS: A literature search was conducted to identify
      Australian studies and programs published from 2002 to 2008 which examined
      strategies and activities for improving medication safety in acute care. RESULTS
      AND CONCLUSION: Since 2002 there has been significant progress in strategies to
      improve prescription writing in hospitals with the introduction of a National
      Inpatient Medication Chart. There are also systems in place to ensure a
      nationally coordinated approach to the ongoing optimisation of the chart.
      Progress has been made with Australian research examining the implementation of
      computerised prescribing systems with clinical decision support. These studies
      have highlighted barriers and facilitators to the introduction of such systems
      that can inform wider implementation. However, Australian studies assessing
      outcomes of this strategy on medication incidents or patient outcomes are still
      lacking. In studies assessing education for reducing medication errors, academic
      detailing has been demonstrated to reduce errors in prescriptions for Schedule 8
      medicines and a program was shown to be effective in reducing error prone
      prescribing abbreviations. Published studies continue to support the role of
      clinical pharmacist services in improving medication safety. Studies on
      strategies to improve communication between different care settings, such as
      liaison pharmacist services, have focussed on implementation issues now that
      funding is available for community-based services. Double checking versus single
      checking by nurses and patient self-administration in hospital has been assessed
      in small studies. No new studies were located assessing the impact of individual
      patient medication supply, adverse drug event alerts or bar coding. There is
      still limited research assessing the impact of an integrated systems approach on
      medication safety in Australian acute care.

PMID- 19772664
TI  - The roles of tumor necrosis factor-alpha in colon tight junction protein
      expression and intestinal mucosa structure in a mouse model of acute liver
      failure.
AB  - BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a common clinical disease
      and one of the most severe complications of acute liver failure (ALF). Although
      the mechanism responsible for SBP is unclear, cytokines play an important role.
      The aim of this study was to investigate the effects of tumor necrosis factor
      alpha (TNF-alpha) on the structure of the intestinal mucosa and the expression of
      tight junction (Zona Occludens 1; ZO-1) protein in a mouse model of ALF. METHODS:
      We induced ALF using D-galactosamine/lipopolysaccharide (GalN/LPS) or GalN/TNF
      alpha and assessed the results using transmission electron microscopy,
      immunohistochemistry, Western blotting, ELISA and real-time quantitative PCR. The
      effects of administration of anti-TNF-alpha IgG antibody or anti-TNF-alpha R1
      antibody before administration of GalN/LPS or GalN/TNF-alpha, respectively, on
      TNF-alpha were also assessed. RESULTS: Morphological abnormalities in the
      intestinal mucosa of ALF mice were positively correlated with serum TNF-alpha
      level. Electron microscopic analysis revealed tight junction (TJ) disruptions,
      epithelial cell swelling, and atrophy of intestinal villi. Gut bacteria invaded
      the body at sites where TJ disruptions occurred. Expression of ZO-1 mRNA was
      significantly decreased in both ALF models, as was the level of ZO-1 protein.
      Prophylactic treatment with either anti-TNF-alpha IgG antibody or anti-tumor
      necrosis factor-a receptor1 (anti-TNF-alpha R1) antibody prevented changes in
      intestinal tissue ultrastructure and ZO-1 expression. CONCLUSION: TNF-alpha
      affects the structure of the intestinal mucosa, decreases expression of ZO-1, and
      affects the morphology of the colon in a mouse model of ALF. It also may
      participate in the pathophysiological mechanism of SBP complicated to ALF.

PMID- 19772665
TI  - Improving outcomes for ill and injured children in emergency departments:
      protocol for a program in pediatric emergency medicine and knowledge translation
      science.
AB  - Approximately one-quarter of all Canadian children will seek emergency care in
      any given year, with the two most common medical problems affecting children in
      the emergency department (ED) being acute respiratory illness and injury.
      Treatment for some medical conditions in the ED remains controversial due to a
      lack of strong supporting evidence. The purpose of this paper is to describe a
      multi-centre team grant in pediatric emergency medicine (PEM) that has been
      recently funded by the Canadian Institutes of Health Research (CIHR). This
      program of research integrates clinical research (in the areas of acute
      respiratory illness and injury) and knowledge translation (KT). This initiative
      includes seven distinct projects that address the objective to generate new
      evidence for clinical care and KT in the pediatric ED. Five of the seven research
      projects in this team grant make significant contributions to knowledge
      development in KT science, and these contributions are the focus of this paper.
      The research designs employed in this program include: cross-sectional surveys,
      randomized controlled trials (RCTs), quasi-experimental designs with interrupted
      time-series analysis and staggered implementation strategies, and qualitative
      designs. This team grant provides unique opportunities for making important KT
      methodological developments, with a particular focus on developing a better
      theoretical understanding of the causal mechanisms and effect modifiers of
      different KT interventions.

PMID- 19772667
TI  - Deep sequencing of Brachypodium small RNAs at the global genome level identifies
      microRNAs involved in cold stress response.
AB  - BACKGROUND: MicroRNAs (miRNAs) are endogenous small RNAs having large-scale
      regulatory effects on plant development and stress responses. Extensive studies
      of miRNAs have only been performed in a few model plants. Although miRNAs are
      proved to be involved in plant cold stress responses, little is known for winter
      habit monocots. Brachypodium distachyon, with close evolutionary relationship to
      cool-season cereals, has recently emerged as a novel model plant. There are few
      reports of Brachypodium miRNAs. RESULTS: High-throughput sequencing and whole
      genome-wide data mining led to the identification of 27 conserved miRNAs, as well
      as 129 predicted miRNAs in Brachypodium. For multiple-member conserved miRNA
      families, their sizes in Brachypodium were much smaller than those in rice and
      Populus. The genome organization of miR395 family in Brachypodium was quite
      different from that in rice. The expression of 3 conserved miRNAs and 25
      predicted miRNAs showed significant changes in response to cold stress. Among
      these miRNAs, some were cold-induced and some were cold-suppressed, but all the
      conserved miRNAs were up-regulated under cold stress condition. CONCLUSION: Our
      results suggest that Brachypodium miRNAs are composed of a set of conserved
      miRNAs and a large proportion of non-conserved miRNAs with low expression levels.
      Both kinds of miRNAs were involved in cold stress response, but all the conserved
      miRNAs were up-regulated, implying an important role for cold-induced miRNAs. The
      different size and genome organization of miRNA families in Brachypodium and rice
      suggest that the frequency of duplication events or the selection pressure on
      duplicated miRNAs are different between these two closely related plant species.

PMID- 19772666
TI  - Expression profiling of skeletal muscle following acute and chronic beta2
      adrenergic stimulation: implications for hypertrophy, metabolism and circadian
      rhythm.
AB  - BACKGROUND: Systemic administration of beta-adrenoceptor (beta-AR) agonists has
      been found to induce skeletal muscle hypertrophy and significant metabolic
      changes. In the context of energy homeostasis, the importance of beta-AR
      signaling has been highlighted by the inability of beta(1-3)-AR-deficient mice to
      regulate energy expenditure and susceptibility to diet induced obesity. However,
      the molecular pathways and gene expression changes that initiate and maintain
      these phenotypic modulations are poorly understood. Therefore, the aim of this
      study was to identify differential changes in gene expression in murine skeletal
      muscle associated with systemic (acute and chronic) administration of the beta(2)
      AR agonist formoterol. RESULTS: Skeletal muscle gene expression (from murine
      tibialis anterior) was profiled at both 1 and 4 hours following systemic
      administration of the beta(2)-AR agonist formoterol, using Illumina 46K mouse
      BeadArrays. Illumina expression profiling revealed significant expression changes
      in genes associated with skeletal muscle hypertrophy, myoblast differentiation,
      metabolism, circadian rhythm, transcription, histones, and oxidative stress.
      Differentially expressed genes relevant to the regulation of muscle mass and
      metabolism (in the context of the hypertrophic phenotype) were further validated
      by quantitative RT-PCR to examine gene expression in response to both acute (1-24
      h) and chronic administration (1-28 days) of formoterol at multiple timepoints.
      In terms of skeletal muscle hypertrophy, attenuation of myostatin signaling
      (including differential expression of myostatin, activin receptor IIB, phospho
      Smad3 etc) was observed following acute and chronic administration of formoterol.
      Acute (but not chronic) administration of formoterol also significantly induced
      the expression of genes involved in oxidative metabolism, including hexokinase 2,
      sorbin and SH3 domain containing 1, and uncoupling protein 3. Interestingly,
      formoterol administration also appeared to influence some genes associated with
      the peripheral regulation of circadian rhythm (including nuclear factor
      interleukin 3 regulated, D site albumin promoter binding protein, and
      cryptochrome 2). CONCLUSION: This is the first study to utilize gene expression
      profiling to examine global gene expression in response to acute beta(2)-AR
      agonist treatment of skeletal muscle. In summary, systemic administration of a
      beta(2)-AR agonist had a profound effect on global gene expression in skeletal
      muscle. In terms of hypertrophy, beta(2)-AR agonist treatment altered the
      expression of several genes associated with myostatin signaling, a previously
      unreported effect of beta-AR signaling in skeletal muscle. This study also
      demonstrates a beta(2)-AR agonist regulation of circadian rhythm genes,
      indicating crosstalk between beta-AR signaling and circadian cycling in skeletal
      muscle. Gene expression alterations discovered in this study provides insight
      into many of the underlying changes in gene expression that mediate beta-AR
      induced skeletal muscle hypertrophy and altered metabolism.

PMID- 19772668
TI  - Possible transmission of Mycobacterium avium subspecies paratuberculosis through
      potable water: lessons from an urban cluster of Crohn's disease.
AB  - A "cluster" of patients refers to the geographic proximity of unrelated patients
      with the same disease and suggests a common environmental cause for that disease.
      Clusters of patients with Crohn's disease have been linked to the presence of an
      infectious microorganism in unpasteurized milk and cheese, untreated water
      supplied by wells or springs, animal manure used as fertilizer for family
      vegetable gardens, and bodies of water contaminated by agricultural runoff.
      Mycobacterium avium subspecies paratuberculosis (MAP) is the suspected cause of
      Crohn's disease. MAP causes a disease in dairy cows and other animals that is
      similar to Crohn's disease, called Johne's ('Yo-knees') disease or
      paratuberculosis. Dairy cows with Johne's disease secrete MAP into their milk and
      excrete MAP into their feces. MAP is present in untreated water such as well
      water, in bodies of water contaminated by agricultural runoff, and in
      unpasteurized milk and cheese. The "treatment" of "tap" water to make it
      "drinkable" or "potable" by the processes of sedimentation, filtration and
      chlorination has little to no effect on MAP. MAP is so resistant to chlorine
      disinfection that such disinfection actually selects for its growth. Other
      subspecies of Mycobacterium avium grow in biofilms present on tap water pipes.
      Despite the documented presence of MAP in tap water and its probable growth on
      tap water pipes, clusters of Crohn's disease have not previously been described
      in relationship to tap water pipes supplying patients' homes. This report
      describes three unrelated individuals who lived on the same block along a street
      in a midwestern American city and developed Crohn's disease within four years of
      each other in the 1960's. A common tap water pipe supplied their homes. This is
      the first reported cluster of Crohn's disease possibly linked to fully treated
      drinking water, and is consistent with previously reported clusters of Crohn's
      disease linked to an infectious microorganism in water.

PMID- 19772669
TI  - Intratracheal synthetic CpG oligodeoxynucleotide causes acute lung injury with
      systemic inflammatory response.
AB  - Bacterial genome is characterized by frequent unmethylated cytosine-phosphate
      guanine (CpG) motifs. Deleterious effects can occur when synthetic
      oligodeoxynucleotides (ODN) with unmethylated CpG dinucleotides (CpG-ODN) are
      administered in a systemic fashion. We aimed to evaluate the effect of
      intratracheal CpG-ODN on lung inflammation and systemic inflammatory response.
      C57BL/6J mice received intratracheal administration of CpG-ODN (0.01, 0.1, 1.0,
      10, or 100 microM) or control ODN without CpG motif. Bronchoalveolar lavage (BAL)
      fluid was obtained 3 or 6 h or 1, 2, 7, or 14 days after the instillation and
      subjected to a differential cell count and cytokine measurement. Lung
      permeability was evaluated as the BAL fluid-to-plasma ratio of the concentration
      of human serum albumin that was injected 1 h before euthanasia. Nuclear factor
      (NF)-kappaB DNA binding activity was also evaluated in lung homogenates.
      Intratracheal administration of 10 microM or higher concentration of CpG-ODN
      induced significant inflammatory cell accumulation into the airspace. The peak
      accumulation of neutrophils and lymphocytes occurred 1 and 2 days after the CpG
      ODN administration, respectively. Lung permeability was increased 1 day after the
      10 microM CpG-ODN challenge. CpG-ODN also induced nuclear translocation of NF
      kappaB and upregulation of various inflammatory cytokines in BAL fluid and
      plasma. Histopathology of the lungs and liver revealed acute lung injury and
      liver damage with necrosis, respectively. Control ODN without CpG motif did not
      induce any inflammatory change. Since intratracheal CpG-ODN induced acute lung
      injury as well as systemic inflammatory response, therapeutic strategies to
      neutralize bacterial DNA that is released after administration of bactericidal
      agents should be considered.

PMID- 19772670
TI  - Graft healing in anterior cruciate ligament reconstruction.
AB  - Successful anterior cruciate ligament reconstruction with a tendon graft
      necessitates solid healing of the tendon graft in the bone tunnel. Improvement of
      graft healing to bone is crucial for facilitating an early and aggressive
      rehabilitation and ensuring rapid return to pre-injury levels activity. Tendon
      graft healing in a bone tunnel requires bone ingrowth into the tendon. Indirect
      Sharpey fiber formation and direct fibrocartilage fixation confer different
      anchorage strength and interface properties at the tendon-bone interface. For
      enhancing tendon graft-to-bone healing, we introduce a strategy that includes the
      use of periosteum, hydrogel supplemented with periosteal progenitor cells and
      bone morphogenetic protein-2, and a periosteal progenitor cell sheet. Future
      studies include the use of cytokines, gene therapy, stem cells, platelet-rich
      plasma, and mechanical stress for tendon-to-bone healing. These strategies are
      currently under investigation, and will be applied in the clinical setting in the
      near future.

PMID- 19772672
TI  - The development and characterisation of a bacterial artificial chromosome library
      for Fragaria vesca.
AB  - BACKGROUND: The cultivated strawberry Fragaria xananassa is one of the most
      economically-important soft-fruit species. Few structural genomic resources have
      been reported for Fragaria and there exists an urgent need for the development of
      physical mapping resources for the genus. The first stage in the development of a
      physical map for Fragaria is the construction and characterisation of a high
      molecular weight bacterial artificial chromosome (BAC) library. METHODS: A BAC
      library, consisting of 18,432 clones was constructed from Fragaria vesca f.
      semperflorens accession 'Ali Baba'. BAC DNA from individual library clones was
      pooled to create a PCR-based screening assay for the library, whereby individual
      clones could be identified with just 34 PCR reactions. These pools were used to
      screen the BAC library and anchor individual clones to the diploid Fragaria
      reference map (FVxFN). FINDINGS: Clones from the BAC library developed contained
      an average insert size of 85 kb, representing over seven genome equivalents. The
      pools and superpools developed were used to identify a set of BAC clones
      containing 70 molecular markers previously mapped to the diploid Fragaria FVxFN
      reference map. The number of positive colonies identified for each marker
      suggests the library represents between 4x and 10x coverage of the diploid
      Fragaria genome, which is in accordance with the estimate of library coverage
      based on average insert size. CONCLUSION: This BAC library will be used for the
      construction of a physical map for F. vesca and the superpools will permit
      physical anchoring of molecular markers using PCR.

PMID- 19772671
TI  - Distribution of periodontopathic bacterial species in Japanese children with
      developmental disabilities.
AB  - BACKGROUND: Recent developments in molecular biological techniques have enabled
      rapid detection of periodontopathic bacterial species in clinical specimens.
      Accumulated evidence suggests that detection of specific bacterial species
      enables identification of subjects at high risk for the onset of periodontitis.
      We investigated the distribution of 10 selected periodontopathic bacterial
      species in dental plaque specimens obtained from children with disabilities who
      were attending daycare centers. METHODS: A total of 187 children (136 boys, 51
      girls) aged 1-6 years old and diagnosed with such disabilities as mental
      retardation, cerebral palsy, and autism, participated in the study. Subgingival
      dental plaque specimens were collected from the buccal side of the maxillary left
      second primary molar after a clinical examination. Bacterial DNA was extracted
      from the specimens and PCR analyses were carried out to detect 10 selected
      periodontopathic species using specific primers for each. In addition,
      statistical analyses were performed to analyze the correlations among clinical
      parameters and the detected species. RESULTS: The most frequently detected
      species was Capnocytophaga sputigena (28.3%), followed by Aggregatibacter
      actinomycetemcomitans (20.9%) and Campylobacter rectus (18.2%). Eikenella
      corrodens, Capnocytophaga ochracea, and Prevotella nigrescence were detected in
      approximately 10% of the specimens, whereas Treponema denticola, Tannerella
      forsythia, and Prevotella intermedia were rarely found, and Porphyromonas
      gingivalis was not detected in any of the subjects. The total numbers of detected
      species were positively correlated with the age of the subjects. There were 10
      subjects with positive reactions for T. denticola and/or T. forsythia, in whom
      the total number of bacterial species was significantly higher as compared to the
      other subjects. Furthermore, subjects possessing C. rectus showed significantly
      greater values for periodontal pocket depth, gingival index, and total number of
      species. CONCLUSION: We found that approximately one-fourth of the present
      subjects with disabilities who possessed at least one of T. denticola, T.
      forsythia, and C. rectus were at possible risk for periodontitis. Follow-up
      examinations as well as preventive approaches should be utilized for such
      individuals.

PMID- 19772673
TI  - Associations between general self-efficacy and health-related quality of life
      among 12-13-year-old school children: a cross-sectional survey.
AB  - BACKGROUND: While research on school children's health has mainly focused on risk
      factors and illness, few studies have examined aspects of health promotion. Thus,
      this study focuses on health promotional factors including general self-efficacy
      (GSE) and health-related quality of life (HRQOL). GSE refers to a global
      confidence in coping ability across a wide range of demanding situations, and is
      related to health. The purpose of this study was to examine associations between
      GSE and HRQOL, and associations between HRQOL and socio-demographic
      characteristics. Knowledge of these associations in healthy school children is
      currently lacking. METHODS: During 2006 and 2007, 279 school children in the
      seventh grade across eastern Norway completed a survey assessing their GSE and
      HRQOL. The children were from schools that had been randomly selected using
      cluster sampling. T-tests were computed to compare mean subscale values between
      HRQOL and socio-demographic variables. Single and multiple regression analyses
      were performed to explore associations among GSE, HRQOL and socio-demographic
      variables. RESULTS: Regression analyses showed a significant relationship between
      increasing degrees of GSE and increasing degrees of HRQOL. In analyses adjusted
      for socio-demographic variables, boys scored higher than girls on self-esteem.
      School children from single-parent families had lower scores on HRQOL than those
      from two-parent families, and children who had relocated within the last five
      years had lower scores on HRQOL than those who had not relocated. CONCLUSION: The
      strong relationship between GSE and HRQOL indicates that GSE might be a resource
      for increasing the HRQOL for school children.

PMID- 19772674
TI  - Saffron is a monomorphic species as revealed by RAPD, ISSR and microsatellite
      analyses.
AB  - BACKGROUND: Saffron (Crocus sativus) is considered the world's most expensive
      spice. Used mainly as a colorant for foodstuffs, it is highly appreciated for its
      aromatic and flavouring properties. Since no molecular markers for this species
      have been found in the literature, the objective of this study was to determine
      whether phenotypical differences found in C. sativus were supported by molecular
      analyses. FINDINGS: Thirty primers from Operon Technologies were used in random
      amplified polymorphic DNA (RAPD) analysis, forty eight primers were screened
      using intersimple sequence repeats (ISSR) method and fifteen primers derived from
      a microsatellites library flanking sequences with repeat motifs were assayed in
      forty three isolates of C. sativus from eleven different countries and a C.
      kotschyanus isolate was used as outgroup. No polymorphic bands were detected in
      any of the accessions combining the different approaches used in this study.
      CONCLUSION: According to our findings, all accessions appear identical clones,
      not only because morphological characters but also at a molecular level. These
      data strongly suggested that C. sativus is a monomorphic species. Thus, genome
      sequencing is needed to find molecular markers for saffron.

PMID- 19772676
TI  - Carcinosarcoma of the ovary a review.
AB  - Carcinosarcoma of the ovary, also referred to as mixed mullerian tumor of the
      ovary, is a rare and aggressive tumor. This tumor type is unique in that it
      contains malignant epithelial and stromal elements. The average survival for a
      woman diagnosed with carcinosarcoma of the ovary is less than 2 years. Due to the
      rarity of this tumor, the optimal treatment for carcinosarcoma of the ovary has
      not been determined. We review the pathology, risk factors, and current treatment
      recommendations for carcinosarcoma of the ovary.

PMID- 19772677
TI  - Tubo-ovarian abscess management options for women who desire fertility.
AB  - Tubo-ovarian abscess (TOA), a serious sequela of pelvic inflammatory disease,
      occurs usually in women of ages 20 to 40. Up to 59% of these women are
      nulliparous. Traditionally, pregnancy rates after TOA are estimated to be 15% or
      less. Current proposed management algorithms for TOA do not include a separate
      pathway for women of reproductive age who may desire future pregnancies. A
      MEDLINE search and extensive review of published literature was undertaken to
      study management options for patients with TOA, and to compare rates of
      responders, pregnancies and complications associated with each management option.
      If intra-abdominal rupture is suspected, and patients are treated with fertility
      preserving, conservative surgery, reported pregnancy rate is 25%. If no rupture
      is suspected and patients are treated with medical management alone, reported
      pregnancy rates vary between 4% and 15%. If no rupture is suspected, and the
      treatment is medical management with immediate laparoscopic drainage within 24
      hours, reported pregnancy rates vary between 32% and 63%. Laparoscopy should be
      considered to all patients with TOA who desire future conception. Overall, the
      advantages of immediate laparoscopy allow for an accurate diagnosis, effective
      treatment under magnification with minimal complications, possibly faster
      response rates with shorter hospitalization times and decreased infertility.

PMID- 19772675
TI  - Inactivating the spindle checkpoint kinase Bub1 during embryonic development
      results in a global shutdown of proliferation.
AB  - BACKGROUND: Bub1 is a component of the spindle assembly checkpoint, a
      surveillance mechanism that maintains chromosome stability during M-phase. Bub1
      is essential during the early stages of embryogenesis, with homozygous BUB1-null
      mice dying shortly after day E3.5. Bub1 is also required later during
      embryogenesis; inactivation of BUB1 on day E10.5 appears to rapidly block all
      further development. However, the mechanism(s) responsible for this phenotype
      remain unclear. FINDINGS: Here we show that inactivating BUB1 on day E10.5 stalls
      embryogenesis within 48 hours. This is accompanied by a global shutdown of
      proliferation, widespread apoptosis and haemorrhaging. CONCLUSION: Our results
      suggest that Bub1 is required throughout the developing embryo for cellular
      proliferation. Therefore, Bub1 has been shown to be essential in all scenarios
      analyzed thus far in mice: proliferation of cultured fibroblasts,
      spermatogenesis, oogenesis and both early and late embryonic development. This
      likely reflects the fact that Bub1 has dual functions during mitosis, being
      required for both SAC function and chromosome alignment.

PMID- 19772678
TI  - Heterotopic cesarean scar pregnancy: how should it be managed?
AB  - Heterotopic cesarean scar pregnancy is an extremely rare condition that may cause
      life-threatening complications. A 24-year-old woman gravida 2, para 1, presented
      with vaginal bleeding. Vaginal sonography demonstrated 2 gestational sacs
      containing viable embryos, one located in the uterine fundus and the other in the
      previous cesarean scar. Fetal reduction of the cesarean scar pregnancy was
      performed with intracardiac KCl injection and the ongoing intrauterine pregnancy
      was delivered by cesarean section at 34 week's gestation. To prevent serious
      complications and preserve intrauterine pregnancy, heterotopic cesarean scar
      pregnancy must be diagnosed early in gestation. Favorable pregnancy outcome can
      be achieved with conservative management. However, such management increases the
      risk of massive bleeding during ongoing pregnancy and cesarean section.